PMID- 15553487
TI  - Monitoring activated sludge settling properties using image analysis.
AB  - The goal of this study is to develop a monitoring system for activated sludge
      properties, as this is an essential tool in the battle against filamentous
      bulking. A fully automatic image analysis procedure for recognising and
      characterising flocs and filaments in activated sludge images has been optimised
      and subsequently used to monitor activated sludge properties in a lab-scale
      installation. The results of two experiments indicate that the image information
      correlates well with the Sludge Volume Index. It is shown that, at the onset of
      filamentous bulking, there is an increase in total filament length on the one
      hand, and a change in floc shape on the other hand.

PMID- 15553488
TI  - Reduction of coagulant amount added to activated sludge for phosphorus removal.
AB  - Adding coagulant to the activated sludge process is effective in maintaining the
      stability of phosphorus removal. However, the precise mechanisms of the reaction
      and behavior of coagulants and phosphorus are not well known. By introducing a
      new phosphorus removal model (PRM), the behavior of coagulant and phosphorus in
      the process could be described. The experimental data of the effluent phosphorus
      concentration and Fe content in the activated sludge agreed with the values
      calculated by PRM. The amount of coagulant addition to the activated sludge
      process for phosphorus removal is reduced with the enhanced biological phosphorus
      removal process. It is suggested that the amount of reduction is determined by
      using PRM.

PMID- 15553489
TI  - Field evaluation of nanofilm detectors for measuring acidic particles in indoor
      and outdoor air.
AB  - This field evaluation study was conducted to assess new technology designed to
      measure number concentrations of strongly acidic ultrafine particles. Interest in
      these particles derives from their potential to cause adverse health effects.
      Current methods for counting and sizing airborne ultrafine particles cannot
      isolate those particles that are acidic. We hypothesized that the size-resolved
      number concentration of such particles to which people are exposed could be
      measured by newly developed iron nanofilm detectors on which sulfuric acid
      (H2SO4*) droplets produce distinctive ringed reaction sites visible by atomic
      force microscopy (AFM). We carried out field measurements using an array of
      samplers, with and without the iron nanofilm detectors, that allowed indirect
      comparison of particle number concentrations and size-resolved measures of
      acidity. The iron nanofilm detectors are silicon chips (5 mm x 5 mm x 0.6 mm)
      that are coated with iron by vapor deposition. The iron layer was 21.5 or 26 nm
      thick for the two batches used in these experiments. After exposure the detector
      surface was scanned topographically by AFM to view and enumerate the ringed acid
      reaction sites and deposited nonacidic particles. The number of reaction sites
      and particles per scan can be counted directly on the image displayed by AFM.
      Sizes can also be measured, but for this research we did not size particles
      collected in the field. The integrity of the surface of iron nanofilm detectors
      was monitored by laboratory analysis and by deploying blank detectors and
      detectors that had previously been exposed to H2SO4 calibration aerosols. The
      work established that the detectors could be used with confidence in temperate
      climates. Under extreme high humidity and high temperature, the surface film was
      liable to detach from the support, but remaining portions of the film still
      produced reliable data. Exposure to ambient gases in a filtered air canister
      during the field tests did not affect the film quality. Sampling sessions to
      obtain particle measurements were scheduled for two 1-week periods in each of the
      four seasons at a rural site in Tuxedo, New York. This schedule was selected to
      test outdoor performance of the iron nanofilm detectors under a variety of
      weather conditions. To seek possible artifacts caused by local source
      differences, we also sampled outdoors for two 1-week sessions during the winter
      in New York City. Indoor tests were conducted in the cafeteria at the Nelson
      Institute of Environmental Medicine (NIEM) in Tuxedo and in a residence in
      Newburgh, New York. For the outdoor tests we simultaneously deployed several
      particle samplers to obtain several measures: --the number concentration of
      acidic and total particles that penetrated the 100-nm cut size of a microorifice
      impactor (MOI) and were electrically precipitated in an electrostatic aerosol
      sampler (EAS) onto the iron nanofilm detectors; --the number concentrations of
      acidic and total particles estimated from detectors placed in a simple ultrafine
      diffusion monitor (UDM); --the size-fractionated mass concentration of strong
      acids in samples from the submicrometer collection stages of the MOI and from a
      polycarbonate filter, parallel to the EAS, that also collected particles
      penetrating the MOI's 100-nm cut size; and --the number concentration of all
      ambient particles with diameters of 300 nm or smaller, determined using a
      scanning mobility particle sizer (SMPS). In the results from these samplers, the
      mean number concentration of acidic particles ranged from about 100 to 1800/cm3,
      representing 10% to 88% of all ambient ultrafine particles for the different
      seasons and sites. The number concentration did not correlate with the acidic
      mass (hydrogen ion, or H+, content) for particles smaller than 100 nm in
      diameter. This was not surprising because a single 100-nm particle may contain
      the same acid volume as many smaller particles if they are pure acid droplets.
      The ambient concentrations of H+, sulfate (SO4(2-)), and ammonium (NH4+),
      collected on polycarbonate filters and measured as a function of particle size,
      were highest for particles with diameters between 280 and 530 nm, but the size
      distributions also suggested that a small peak of these ions existed in the
      particle size range below 88 nm. The H+ / SO4(2-) ratio was somewhat higher for
      particles below 88 nm, suggesting greater excess acidity for these small
      particles. Our continuous monitoring showed that airborne concentrations of
      ultrafine particles varied substantially with time. The iron nanofilm detectors
      provided a time-integrated number concentration over several days or weeks. The
      counts on the detectors were relatively low for some of the sampling sessions,
      resulting in high statistical errors in calculations. Nonetheless, agreement of
      the mean values was remarkably good for some of the measurements. In future
      tests, longer collection times and new technologies, such as improved particle
      charging methods for electrical precipitation samplers, could provide more
      efficient collection of particles onto the detectors, higher counts, and lower
      count-associated uncertainties. In general, concentrations of ultrafine particles
      determined by AFM analysis of the detectors in the MOI-EAS and UDM appeared to
      underestimate the total number concentration as determined by comparison
      samplers. The ability to monitor airborne acidic particles provided by these iron
      nanofilm detectors enlarges the array of air quality variables that can be
      measured. This may help to resolve some of the outstanding questions related to
      causal relations between demonstrated health effects of ambient particles and
      particulate matter (PM) components.

PMID- 15553490
TI  - Don't get buried. You can find what you need if you stay focused.

PMID- 15553491
TI  - Smart patient's guide. Find a mentor: not just a companion, but a trusted medical
      guide.

PMID- 15553493
TI  - Smart patient's guide. Take charge. Once you decide what you need, work to make
      it happen.

PMID- 15553492
TI  - Smart patient's guide. Go for two. No doctor knows everything. Here's how to get
      another viewpoint.

PMID- 15553494
TI  - Arctic thaw.

PMID- 15553495
TI  - Tiny surviviors.

PMID- 15553496
TI  - Doctor connections.

PMID- 15553498
TI  - Report weighs research on e-mail consultation, finds advantages.

PMID- 15553497
TI  - Overcoming spam blockers.

PMID- 15553499
TI  - Dealing with "freeloaders" and the Web's new search paradigm.

PMID- 15553500
TI  - Frequency shifts in a piezoelectric body due to small amounts of additional mass
      on its surface.

PMID- 15553501
TI  - Minimum-loss short reflectors on 128 degrees LiNbO3.

PMID- 15553502
TI  - New type of linear ultrasonic actuator based on a plate-shaped vibrator with
      triangular grooves.

PMID- 15553503
TI  - Determination of complex coefficients of radially polarized piezoelectric ceramic
      cylindrical shells using thin shell theory.
AB  - A method is presented to determine the complex coefficients eT33, sE11, sE12, and
      d31 of piezoelectric materials. The real parts of these coefficients are
      determined using axially polarized thin discs in the ANSI/IEEE Standard but are
      determined here using radially polarized cylindrical shells. The coefficients are
      determined by iteratively refining them until the values of the low-frequency
      complex admittance, three resonance frequencies, and three bandwidths computed
      using a thin-shell analytical model and the coefficients are very nearly equal to
      measured values. The accuracy of the method is determined by using quantities
      computed using a finite-element model in place of measured values. Measurement
      errors are accounted for by using a resolution of 10 Hz to compute the critical
      frequencies. The differences between the coefficients input to the finite-element
      model and those obtained using the iteration method are the errors. It is shown
      that the method is sufficiently accurate to use thin radially polarized
      cylindrical shells to determine the properties of new materials as well as
      characterize those used in hydrophones or other devices.

PMID- 15553504
TI  - IEN-CsF1 accuracy evaluation and two-way frequency comparison.
AB  - In this paper we report the accuracy evaluation of the Italian primary frequency
      standard IEN-CsF1. We discuss the shifts the frequency standard is corrected for
      and the procedure used for the accuracy evaluation. In the last section we report
      frequency comparisons of our fountain with those of remote laboratories and with
      International Atomic Time.

PMID- 15553505
TI  - High spectral purity microwave oscillator: design using conventional air
      dielectric cavity.
AB  - We report exceptionally low PM noise levels from a microwave oscillator that uses
      a conventional air-dielectric cavity resonator as a frequency discriminator. Our
      approach is to increase the discriminator's intrinsic signal-to-noise ratio by
      use of a high-power carrier signal to interrogate an optimally coupled cavity,
      while the high-level of the carrier is suppressed before the phase detector. We
      developed and tested an accurate model of the expected PM noise that indicates,
      among other things, that a conventional air-dielectric resonator of moderate Q
      will exhibit less discriminator noise in this approach than do more esoteric and
      expensive dielectric resonators tuned to a high-order, high-Q mode and driven at
      the dielectric's optimum

PMID- 15553506
TI  - A cryogenic open-cavity sapphire reference oscillator with low spurious mode
      density.
AB  - In this paper, we describe the implementation of a microwave cryogenic sapphire
      oscillator (CSO) at the Laboratoire de Physique et Metrologie des Oscillateurs.
      In our realization we solved the problem of the spurious modes by operating the
      sapphire resonator in an open cavity. The CSO compared to a hydrogen maser
      demonstrates a frequency stability better than 3 x 10(-14) at short term. Its
      long-term frequency instability of the order of 3 x 10(-12)/day is limited by a
      random walk process. A first attempt to use this reference oscillator to
      characterize other signal sources is presented.

PMID- 15553508
TI  - Finite element analysis on piezoelectric ring transformer.
AB  - The use of a piezoelectric ring as transformer is reported and studied in this
      paper. By using a concentric electrode pattern, a ring-shaped transformer can be
      designed to operate at its high order extensional modes. Lead zirconate titanate
      (PZT) ceramic rings with 12.7-mm outer diameter, 5.1-mm inner diameter and 1.2-mm
      thickness were used to fabricate the prototypes. Three-dimensional (3-D) finite
      element models are built to study and analyze the vibration characteristics of
      the piezoelectric transformers (PTs) using higher order modes (>3). The resonant
      frequencies, mean coupling effect, mode shapes, and other open-circuit
      characteristics are simulated and compared with experimental measurements.
      Prototypes of PTs using mode order three and four were fabricated and
      characterized. Good agreement can be obtained between experimental results and
      finite element model (FEM) simulations. The dimensions for the PTs using higher
      order symmetric extensional modes are optimized by FEM. To avoid mode coupling
      with the thickness mode, the ideal ring thickness has to be less than or equal to
      0.6 mm. The ring PT offers advantages of simple structure and small size. It has
      a good potential in making low cost PT for low-voltage applications.

PMID- 15553509
TI  - Fabrication and modeling of high-frequency PZT composite thick film membrane
      resonators.
AB  - High-frequency, thickness mode resonators were fabricated using a 7 microm
      piezoelectric transducer (PZT) thick film that was produced using a modified
      composite ceramic sol-gel process. Initial studies dealt with the integration of
      the PZT thick film onto the substrate. Zirconium oxide (ZrO2) was selected as a
      diffusion barrier layer and gave good results when used in conjunction with
      silicon oxide (SiO2) as an etch stop layer. Using these conditions, devices were
      produced and the acoustic properties measured and modeled. The resonators showed
      a resonant frequency of about 200 MHz, an effective electromechanical coupling
      coefficient of 0.34, and a Q factor of 22. Modeling was based on a Mason-type
      model that gave good agreement between the experimental data and the simulations.
      The latter showed, for the PZT thick film, an electromechanical coupling
      coefficient of 0.35, a stiffness of 8.65 x 10(10) N x m(-2) and an e33,f
      piezoelectric coefficient of 9 C x m(-2).

PMID- 15553510
TI  - Probing acoustic fields of clinically relevant transducers: the effect of
      hydrophone probes' finite apertures and bandwidths.
AB  - The influence of finite aperture and frequency response of piezoelectric
      ultrasonic hydrophone probes on the free-field pulse intensity integral (PII) and
      mechanical index (MI) was investigated using a comprehensive acoustic wave
      propagation model. The model developed was capable of predicting the true
      pressure-time waveforms at virtually any point in the field. The input to the
      model used pressure amplitude data measured in the immediate vicinity of the
      acoustic source or transducer considered. The experimental verification of the
      model was obtained using a commercially available, 8 MHz, dynamically focused
      linear array and a single element, 5 MHz, focused rectangular source. The
      verification was performed at low and high excitation levels, corresponding to
      linear and nonlinear acoustic wave propagation, respectively. The pressure-time
      waveforms were recorded using piezoelectric polymer hydrophone probes that had
      different sensitivities, frequency responses, bandwidths, and active element
      diameters. The nominal diameters of the probes ranged from 50 to 500 microm, and
      their useable bandwidths varied between 55 and 100 MHz. The PII, used to
      calculate the thermal index (TI), was found to increase with increasing bandwidth
      and decreasing effective aperture of the probes. The MI, another safety
      indicator, also was affected, but to a lesser extent. The corrections predicted
      using the model were used to reduce discrepancies as large as 30% in the
      determination of PII. The results of this work indicate that, by accounting for
      hydrophones' finite aperture and correcting the value of PII, all intensities
      derived from the PII can be corrected for spatial averaging error. The results
      also point out that caution should be exercised when comparing acoustic output
      data. In particular, hydrophone's frequency characteristics of the effective
      diameter and sensitivity are needed to correctly determine the MI, TI, and the
      total acoustic output power produced by an imaging transducer.

PMID- 15553511
TI  - A swept frequency multiplication technique for air-coupled ultrasonic NDE.
AB  - A new technique has been investigated for improving the signals that can be
      obtained in air-coupled nondestruction evaluation (NDE). This relies on the wide
      bandwidth available from polymer-filmed capacitive transducers. The technique
      relies on a swept-frequency "chirp" signal, which is transmitted from a
      transducer in air. The new technique differs from existing time-domain
      correlation techniques, such as pulse compression, in that a single
      multiplication process is performed in the time domain to give a difference
      frequency signal. This then can be isolated easily in the frequency domain. It
      will be demonstrated that this new swept frequency multiplication (SFM) approach
      gives the potential for rapid air-coupled imaging.

PMID- 15553512
TI  - Effect of electric load impedances on the performance of sandwich piezoelectric
      transducers.
AB  - Based on the electromechanical equivalent circuit, the sandwich piezoelectric
      transducer with adjustable resonance frequency is studied. The underlying theory
      of frequency adjustment is its piezoelectric effect. In this paper, the influence
      of electric load impedance (including electric resistance, electric inductance,
      and electric capacitance) on the resonance frequency, the antiresonance
      frequency, and the effective electromechanical coupling coefficient is analyzed
      theoretically and experimentally. It is demonstrated that the electric load
      impedance can change the resonance frequency, the antiresonance frequency, and
      the effective electromechanical coupling coefficient. When the electric load
      resistance is increased, the resonance frequency and the antiresonance frequency
      are increased; the effective electromechanical coupling coefficient has a maximum
      value when the electric load resistance changes. When the electric load
      resistance becomes large, the effect of the electric load resistance on the
      effective electromechanical coupling coefficient is negligible. When the electric
      load inductance is increased, the resonance frequency and the antiresonance
      frequency are decreased, whereas the effective electromechanical coupling
      coefficient is increased. When the electric load capacitance is increased, the
      resonance frequency, the antiresonance frequency, and the effective
      electromechanical coupling coefficient are all decreased. It should be noted that
      when the electric load impedance becomes large, the effect of the electric load
      impedance on the resonance frequency, the antiresonance frequency, and the
      effective electromechanical coupling coefficient of a sandwich piezoelectric
      transducer becomes negligible.

PMID- 15553513
TI  - Guided lamb waves and L-SAFT processing technique for enhanced detection and
      imaging of corrosion defects in plates with small depth-to-wavelength ratio.
AB  - The Lamb synthetic aperture focusing technique (L-SAFT) imaging algorithm in the
      Fourier domain is used to produce Lamb wave imaging in plates while considering
      the wave dispersive properties. This artificial focusing technique produces easy
      to-interpret, modified B-scan type images of Lamb wave inspection results. The
      high level of sensitivity of Lamb waves combined with the L-SAFT algorithm allows
      one to detect and to produce images of corrosion defects with small depth-to
      wavelength ratio. This paper briefly presents the formulated L-SAFT algorithm
      used for Lamb waves and, in more details, some experimental results obtained on
      simulated and real corrosion pits, demonstrating the benefit of combining L-SAFT
      with pulse-echo Lamb wave inspection. The obtained images of the real corrosion
      defects showed detection of pits with a depth-to-wavelength ratio of
      approximately 2/11.

PMID- 15553514
TI  - Film-loaded SAW waveguides for integrated acousto-optical polarization
      converters.
AB  - We report on a detailed theoretical and experimental investigation of film-loaded
      surface acoustic wave (SAW) waveguides in lithium niobate (LiNbO3) for integrated
      acousto-optical (AO) polarization converters. The numerical analysis is based on
      both a scalar and a full-vectorial model. Dispersion plots and figures of merit
      for several structures are given, which lead to design parameters for optimized
      polarization converters. It is pointed out that very attractive structures are
      metal/dielectric/LiNbO3 strip waveguides and dielectric/LiNbO3 slot waveguides,
      in which metal is either gold (Au) or aluminum (Al), and the dielectric film is
      an optical transparent material such as silicon oxide (SiO2), magnesium oxide
      (MgO), or aluminium oxide (Al2O3). Polarization converters with the designed
      acoustical waveguides have been realized and characterized by optical conversion
      and laser probing measurements.

PMID- 15553515
TI  - Simulation of characteristics of a LiNbO3/diamond surface acoustic wave.
AB  - High-frequency surface acoustic wave (SAW) devices based on diamond that have
      been produced to date utilize the SiO2/ZnO/diamond structure, which shows
      excellent characteristics of a phase velocity of over 10,000 m/s with a zero
      temperature coefficient; this structure has been successfully applied to high
      frequency narrowband filters and resonators. To expand material systems to
      wideband applications, c-axis-oriented LiNbO3 on diamond was studied and a
      coupling coefficient up to 9.0% was estimated to be obtained. In this paper, the
      characteristics of LiNbO3/diamond with the assumption that the LiNbO3 film is a
      single crystal have been studied by theoretical calculations to find higher
      coupling coefficient conditions. Calculations are made for the phase velocity,
      the coupling coefficient, and the temperature coefficient of the Rayleigh wave
      and its higher mode Sezawa waves. As a result, LiNbO3/diamond is found to offer a
      very high electromechanical coupling coefficient of up to 16% in conjunction with
      a high phase velocity of 12,600 m/s and a small temperature coefficient of 25
      ppm/deg. This characteristic is suitable for wide bandwidth applications in high
      frequency SAW devices.

PMID- 15553516
TI  - Characterization and assessment of an integrated matching layer for air-coupled
      ultrasonic applications.
AB  - A novel ultrasonic matching layer for improving coupling between piezoelectric
      transducers and an air load is presented and the results of a theoretical and
      experimental program of work are provided. A combination of a porous material
      that has very low acoustic impedance with a low-density rubber material forms the
      basis of the approach. These matching layers were first analyzed experimentally
      using scanning electron and optical microscopy to determine the microscopic
      structure. Air-coupled resonance measurements were then performed to reveal the
      acoustic parameters of the individual layers that were identified within this
      multilayered structure. These data were then incorporated into a conventional
      linear model, and this has been verified and used to study performance and
      produce designs. Close correlation between experiment and theory is demonstrated.
      The most efficient designs have been implemented in a pitch/catch air-coupled
      system, and an improvement in received signal amplitude of 30 dB was achieved
      when compared with the unmatched case.

PMID- 15553520
TI  - The schoch effect to distinguish between different liquids in closed containers.

PMID- 15553518
TI  - A miniaturized catheter 2-D array for real-time, 3-D intracardiac
      echocardiography.
AB  - The design, fabrication, and characterization of a 112 channel, 5 MHz, two
      dimensional (2-D) array transducer constructed on a six layer flexible polyimide
      interconnect circuit is described. The transducer was mounted in a 7 Fr (2.33 mm
      outside diameter) catheter for use in real-time intracardiac volumetric imaging.
      Two transducers were constructed: one with a single silver epoxy matching layer
      and the other without a matching layer. The center frequency and -6 dB fractional
      bandwidth of the transducer with a matching layer were 4.9 MHz and 31%,
      respectively. The 50 omega pitch-catch insertion loss was 80 dB, and the typical
      interelement crosstalk was -30 dB. The final element yield was greater than 97%
      for both transducers. The transducers were used to acquire real-time, 3-D images
      in an in vivo sheep model. We present in vivo images of cardiac anatomy obtained
      from within the coronary sinus, including the left and right atria, aorta,
      coronary arteries, and pulmonary veins. We also present images showing the
      manipulation of a separate electrophysiological catheter into the coronary sinus.

PMID- 15553521
TI  - Medicare payment increase begins; phases out over six years.

PMID- 15553522
TI  - CO2 ... it's more than a gas!

PMID- 15553523
TI  - Scared to death: the irrational response we forget.

PMID- 15553524
TI  - Senior tour.

PMID- 15553525
TI  - Chris Callsen on special operations.

PMID- 15553526
TI  - Making meetings matter.

PMID- 15553527
TI  - Inviting injury.
AB  - PPE equals one thing personal safety. Employers must ensure that responders are
      provided with applicable PPE and taught how to use it for the incidents and
      environments they may encounter. Responders who fail to wear PPE or wear it
      inappropriately invite injury. Employers should not assume that responders know
      how or even when to use certain PPE--regular in-service training should be
      provided. As a responder, you have a responsibility to always undertake safe
      actions. If you follow this monthly column, you have no doubt heard me say
      repeatedly that nothing, absolutely nothing, supercedes safety. You are not an
      expendable resource. Wear your PPE and, most important, wear it the right way.

PMID- 15553528
TI  - Chem producers take initiative in facility protection.

PMID- 15553529
TI  - Dripping toward disaster: EMS in crisis.

PMID- 15553530
TI  - Weighty matters: transporting obese patients.
AB  - EMS personnel face a continuing challenge. Obese patients are prone to medical
      conditions exacerbated by their weight. Nevertheless, they deserve skilled and
      compassionate care. Don't exceed your equipment's weight capacity, appoint a
      safety officer and maintain adequate staffing.

PMID- 15553531
TI  - Generation next: club drugs.

PMID- 15553532
TI  - Managing antidepression overdoses.
AB  - Depression is a physiological disorder that is medically treated by increasing
      the bodily amount of one or all of the following neurotransmitters: serotonin,
      dopamine and norepinephrine. Although there are seven distinct classes of
      antidepressants, prehospital care professionals should at minimum be able to
      distinguish the monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants
      (TCAs), selective serotonin reuptake inhibitors (SSRIs), and newer
      antidepressants that are none of these. Monoamine oxidase inhibitors have severe,
      potentially life-threatening interactions with a variety of medications,
      including the paramedic drug meperidine, as well as with many common foods. An
      overdose of tricyclic antidepressants can cause lethal cardiac irregularities.
      Tricyclics are toxic to children in very small doses. A patient who has overdosed
      on TCAs may be walking and talking when you first arrive, then quickly
      deteriorate and die before your eyes. The treatment for TCA overdose is sodium
      bicarbonate; refer to your medical direction for dosages and indications. A
      common indication of TCA overdose, secondary to the patient's having access to
      the drugs, is widening of the QRS complex to greater than 0.12 seconds. Serotonin
      syndrome is often the result of taking a new generation antidepressant, such as
      an SSRI, while there is still TCA or MAOI in the bloodstream.

PMID- 15553533
TI  - Case conference: EMS response to meningococcal meningitis.
AB  - This article presents timelines for two emergency medical incidents in which an
      atypical, unsafe scene was detected and managed by paramedics. Both incidents
      involved patients who were correctly diagnosed with meningococcal meningitis and
      meningococcemia (septic shock) by the paramedics on scene. A case review is
      presented in moderated format to discuss meningococcal disease and to present
      several points about scene safety in the setting of an infectious disease
      emergency, management principles for occupational exposures, and the local
      emergency management approach to a potential public health emergency in a
      municipality that does not have its own health department or health officer.

PMID- 15553534
TI  - Extra riders: surprises in pregnancy transport.

PMID- 15553535
TI  - Frontline biological and chemical agent detection.

PMID- 15553536
TI  - EMS Magazine's Resource Guide: infection control.

PMID- 15553537
TI  - Ouch! Sharps and the needle-stick challenge.
AB  - Needle-sticks and related sharps exposures occur all too often in the prehospital
      setting. Prevention is the goal. If the unfortunate happens, report the exposure
      to your employer immediately, following the steps listed above, to ensure
      appropriate follow-up care. ESO management should establish sound policy with
      supporting procedures so that every provider can comply with the applicable
      expectations.

PMID- 15553538
TI  - The science and technology inside a quality glove.

PMID- 15553539
TI  - Latex allergy: current and future.

PMID- 15553540
TI  - Views from the field. EMS Magazine's Third Annual Emerging Leaders in EMS Forum.

PMID- 15553542
TI  - Patient care begins with "R".

PMID- 15553541
TI  - Joint collaboration enhances response to athletic emergencies.

PMID- 15553543
TI  - Hydrogen cyanide in fire smoke: an underappreciated threat.

PMID- 15553544
TI  - The human resources code. Managing employee performance problems.

PMID- 15553545
TI  - EMS in Cuba: a student's view.

PMID- 15553546
TI  - Health and safety at the top of the world.

PMID- 15553547
TI  - Improvise and overcome: bringing EMS to Kenya, Part 1.

PMID- 15553548
TI  - Challenges in teaching evidence-based practice.

PMID- 15553549
TI  - School nursing: not just band-aids any more!
AB  - ISSUES AND PURPOSE: School nursing has changed dramatically over the past 25
      years. The complex social and physical needs of children require an expanded role
      with advanced knowledge and skills. The school nurse functions as health
      promoter, health educator, collaborator, and researcher. Issues related to
      advanced practice and policy development also affect school nursing practice.
      CONCLUSIONS/PRACTICE IMPLICATIONS: The current emphasis on educational
      accountability and improvement of standardized test scores has mandated close
      examination of resource allocation. There is a need to appreciate an expanded
      role for the school nurse, as the provision of healthcare services in the school
      will afford children an increased capacity to learn, thus improving school
      performance.

PMID- 15553550
TI  - Parent-child interaction and attention regulation in children born prematurely.
AB  - ISSUES AND PURPOSE: The goal of this pilot study was to understand attention
      behaviors in extremely low-birth-weight (ELBW) children within the context of
      parent-child interactions and their relation to the child's independent
      performance. DESIGN AND METHODS: Parent-child and child-alone puzzle matching
      tasks, demographics, and IQ were measured in a sample of 15 4-year-olds who
      weighed <1000 g at birth and were free from major disability. RESULTS: A self
      regulated and efficient strategy during the parent-child puzzle was related to
      using an efficient strategy when working alone. Attention regulation during the
      parent-child puzzle was related to accuracy in the child-alone task. Parents
      appeared to be regulating attention appropriately. PRACTICE IMPLICATIONS:
      Understanding the mechanisms of attention regulation in ELBW children could lead
      to specific interventions to support parents in strengthening their children's
      self-regulatory functioning.

PMID- 15553551
TI  - Effect of education on school-age children's and parents' asthma management.
AB  - ISSUES AND PURPOSE: Asthma affects 7.4% of school-age children, with poor
      children or members of ethnic minorities disproportionately affected. DESIGN AND
      METHODS: A quasiexperimental, year-long pilot study tested the effectiveness of
      an intervention that included school-based small-group education for children
      with home-based education for parents. Pretest and two posttest measures were
      collected. RESULTS: Forty-four families completed the study (41% African
      American, 36% European American, 23% Mexican American), with 46% coming from poor
      or working-class families. Asthma management in the treatment group was lower
      than the comparison group at baseline, but improved significantly at 6 months and
      stabilized at 12 months, a trend that was most pronounced among the poorer
      children. PRACTICE IMPLICATIONS: Improvements in asthma management point to the
      need for ongoing asthma education to address learning needs of the children and
      families.

PMID- 15553553
TI  - Staff nurses as recruiters.

PMID- 15553552
TI  - Pediatric nursing in space environments.

PMID- 15553554
TI  - Improving the health and well being of Wisconsin's children: the KidsFirst
      agenda.

PMID- 15553555
TI  - Increasing access to affordable contraception: a look at the Wisconsin Medicaid
      Family Planning Waiver.
AB  - Approximately half of all pregnancies in the United States are unintended. The
      purpose of the Family Planning Waiver, a Wisconsin Medicaid program implemented
      in 2003, is to expand access to contraceptive care and other reproductive health
      services. The waiver provides women with birth control services and supplies,
      emergency contraception, routine reproductive health exams, and diagnosis and
      treatment of sexually transmitted diseases. With greater availability of
      contraception, the expected outcome is a reduction of unintended pregnancies and
      subsequent therapeutic abortion, which results in a decreased financial burden to
      the state, as well as an opportunity for women to experience motherhood when they
      are emotionally prepared to do so.

PMID- 15553556
TI  - Wisconsin Birth Defects Registry collecting data.
AB  - Wisconsin Statute 253.12 was enacted in May 2000 to create the Wisconsin Birth
      Defects Registry (WBDR), replacing the Birth and Developmental Outcome Monitoring
      Program, a previous birth defects and developmental disabilities reporting system
      initiated in 1989. In the summer of 2004, the new registry began collecting
      demographic, diagnostic, and identifying information for children from birth to 2
      years of age who are born with reportable birth defects and/or are receiving
      health care services for them in Wisconsin. This article describes the
      development of the registry and outlines expectations for reporting of birth
      defects.

PMID- 15553557
TI  - "Back to sleep" saves babies from SIDS in Wisconsin... there's still more to do.

PMID- 15553558
TI  - Wisconsin Medical Home Learning Collaborative: a model for implementing practice
      change.
AB  - A child with special health care needs is defined as having, or are at increased
      risk for, a chronic physical, developmental, behavioral, or emotional condition
      that requires health and related services of a type or amount beyond that
      required by children generally. In Wisconsin nearly 14% of children are
      identified as having or being at risk for special health care needs. Healthy
      People 2010 and the federal Child Health Maternal Bureau have challenged each
      state to "assure access to ongoing comprehensive health care through a medical
      home" for all children with special health care needs. A medical home is defined
      as "an approach to providing continuous and comprehensive primary pediatric
      care." States are challenged to translate the concepts of medical home to
      clinical practice activities. This article discusses Wisconsin's participation in
      a national Medical Home Learning Collaborative and Wisconsin's replication of the
      Collaborative as a means to develop practical strategies for practice
      implementation of a medical home.

PMID- 15553559
TI  - ABC for health: funding medical home services for Wisconsin children with special
      health care needs.
AB  - Medical home services for families with children with special health care needs
      can provide needed help for families struggling to gain access to coverage and
      needed services. Wisconsin, through Medicaid Early and Periodic Screening,
      Diagnosis, and Treatment Services, has an opportunity to provide this important
      and necessary service.

PMID- 15553560
TI  - Smoking cessation and prevention in women of reproductive age: resources and
      partnerships for physicians.
AB  - The importance of smoking cessation and prevention as a women's issue is clear-
      physicians who interact with women of reproductive age are in an excellent
      position to influence women's decisions to quit smoking. This paper provides
      information on community resources physicians can offer to their patients to help
      support their cessation attempts and describes a new partnership opportunity that
      physicians can become involved with.

PMID- 15553561
TI  - Regionalization of perinatal care in Wisconsin: a changing health care
      environment.
AB  - Wisconsin has recently experienced a rapid increase in the number of neonatal
      intensive care units (NICUs), from 6 in the 1970s to 18 in 2003. Over the last
      year, the Wisconsin Association for Perinatal Care (WAPC) convened meetings in
      response to threats to regionalized care and worsening of perinatal outcomes,
      noted especially in some racial/ethnic groups. WAPC defined actions to address
      quality improvement, including adoption of designations for levels of care
      published by the American Academy of Pediatrics and the American College of
      Obstetricians and Gynecologists, definition of perinatal outcomes sensitive to
      quality of care, collection and analysis of outcome data, and continued statewide
      discussions about the status of regionalized care and outcomes. WAPC invites
      others to join in cooperative efforts to address quality of care and responsible
      utilization of resources.

PMID- 15553562
TI  - Saving money by spending more.

PMID- 15553563
TI  - Comprehensive approach needed to decrease disparities in dental care.

PMID- 15553564
TI  - Trends in maternal and child health outcomes: where does Wisconsin rank in the
      national context?
AB  - BACKGROUND: The infant mortality rate (IMR), low birth weight (LBW) rate, and
      first trimester entry into prenatal care (PNC) are indicators that reflect the
      health of a population. OBJECTIVE: To examine these indicators in Wisconsin from
      1979 through 2001 and compare them to those of the United States, looking at
      trends and relative rank compared with other states. METHODS: Three-year averages
      for IMR, LBW, and PNC were analyzed for the periods 1979-1981, 1984-1986, 1989
      1991, 1994-1996, and 1999-2001 from data sources published by the Centers for
      Disease Control and Prevention. Wisconsin's rank relative to other states was
      compared for the overall, black, and white populations. RESULTS: Wisconsin's
      overall IMR was consistently at, or slightly better than, the national IMR. From
      1979-1981 to 1999-2001, the US black IMR decreased by 37.4%, while the Wisconsin
      black IMR declined 12.4%; thus, Wisconsin's rank among the states fell from third
      best to 32 among 34 states with a sufficient number of black births. LBW rates
      for Wisconsin's black population were consistently at least twice that of the
      white population. In 1979-1981, early entry into PNC for all Wisconsin women
      (82.9%) was significantly higher than that of the US population (74.1%).
      Wisconsin's early PNC entry rates improved slightly; as other states also
      improved, Wisconsin's ranking dropped. Wisconsin's relative ranks for IMR, LBW,
      and PNC declined for all 3 indicators from 1979-1991 to 1999-2001. DISCUSSION:
      Birth outcome disparities in Wisconsin pose challenges for physicians, public
      health, and private agencies; all must collaborate and act to improve health,
      housing, employment, education, and the social capital and support that makes up
      the fabric of our society.

PMID- 15553565
TI  - Sleep and its disorders in pregnancy.

PMID- 15553566
TI  - The Wisconsin Fetal Alcohol Syndrome Screening Project.
AB  - PROBLEM: Fetal Alcohol Syndrome (FAS) is preventable, under-diagnosed, and under
      reported. Wisconsin rates for alcohol use and binge drinking in childbearing-age
      women exceed the national average. FAS prevalence in Wisconsin has not previously
      been systematically evaluated. METHODS: The Wisconsin Fetal Alcohol Syndrome
      Screening Project (WFASSP) used a multi-stage, multisource prospective population
      based screening methodology to identify children born in 1998-1999 in Southeast
      Wisconsin who met a surveillance case definition for FAS. The 4-stage methodology
      used screening of electronic birth files, abstraction of neonatal medical
      records, and direct assessment of facial features, growth, and development at age
      2 to 3 years. RESULTS: The FAS prevalence rate was 0.23 per 1000 births. Children
      directly evaluated had fewer demographic, pregnancy, and maternal substance use
      risk factors than lost-to-follow-up children. Thirty-two percent of children with
      weight and head circumference below the 10th percentile at birth were
      developmentally delayed and 47% had at least one physical growth delay.
      CONCLUSIONS: The WFASSP methodology identified children who had not previously
      been diagnosed with FAS. Using the combination of weight and head circumference
      below the 10th percentile at birth is a useful methodology for identifying
      children at substantial risk for growth and developmental delays from FAS or
      other unspecified etiologies.

PMID- 15553567
TI  - Pregnancy-associated deaths and pregnancy-related deaths in Wisconsin, 1998-2001.
AB  - BACKGROUND: Although the risk of dying during childbirth or from complications
      afterward has been greatly reduced during the past 100 years, the current rate of
      approximately 1 death in 10,000 live births is still too high. The goal of the US
      Department of Health and Human Services is to reduce this rate by more than half
      by the year 2010. OBJECTIVE: To present Wisconsin data regarding pregnancy
      associated deaths and pregnancy-related deaths. METHODS: Cases in which a woman
      had died during pregnancy or within 1 year of the end of her pregnancy were
      identified, and case-specific data were collected. The Wisconsin Maternal
      Mortality Review Team then conducted systematic reviews of the information,
      summarized issues related to maternal mortality, considered the relationship to
      pregnancy and factors of avoidability, and made recommendations to improve
      maternal health and survival. Finally, pregnancy-associated and pregnancy-related
      mortality ratios were calculated. RESULTS: From 1998 through 2001, 23 Wisconsin
      women died as a result of their pregnancy or from complications up to a year
      later. This gives a Wisconsin pregnancy-related mortality ratio of 8.4 per
      100,000 live births. This ratio was higher in African American women and in women
      who smoked. The primary cause of death was embolic disease. Almost half of the
      pregnancy-related deaths (48%) occurred during the postpartum period, and nearly
      one-quarter (22%) were avoidable. CONCLUSIONS: The disparity in pregnancy-related
      mortality ratios among ethnic groups and the finding of avoidable deaths are
      areas that should be targeted by health care providers and public health workers.
      Six areas on which to focus include the following: addressing racial disparities,
      assuring the performance of autopsies, lifestyle changes related to obesity and
      smoking, and management of embolic and cardiovascular disease, as well as
      postpartum hemorrhage.

PMID- 15553568
TI  - Cost savings associated with smoking cessation for low-income pregnant women.
AB  - Despite the many health risks associated with smoking during pregnancy, it
      remains a chief public health concern with a high prevalence evident at the local
      level. In Wisconsin, the First Breath program was developed to help pregnant
      smokers quit and served 424 women during its pilot phase in 2001 and 2002. This
      cost savings analysis included claims associated with First Breath enrollees who
      were identified within the Wisconsin Medicaid data warehouse. This analysis
      allowed for a comparison of medical claims for women who quit smoking through the
      First Breath program versus those who continued to smoke. Three billing
      categories were included in this analysis: mother's maternity admissions
      (maternal DRG), inpatient neonatal care (neonate DRG), and infant's medical costs
      for the first 6 months of life. Average Medicaid savings per First Breath
      enrollee who quit smoking was 1274 dollars. Applying this savings to the actual
      number of women who quit smoking during the pilot study gives a total savings of
      137,592 dollars for the Medicaid program. Considering the maximum Medicaid cost
      of providing cessation services to all First Breath participants, the return on
      investment associated with the First Breath program is 9 to 1.

PMID- 15553569
TI  - Efforts to quit smoking by parents of children with asthma.
AB  - The objective of this project was to assess the prevalence of (1) tobacco smoke
      exposure at home among children with asthma and (2) efforts to quit smoking by
      their parents. We employed a cross sectional survey of 622 parents of children
      diagnosed by a doctor with asthma. Seventy-five percent of parents reported smoke
      free homes. Overall, 85% of parents pledged to keep smoke-free homes, 92% in
      existing smoke-free homes and 64% in homes with smoke.

PMID- 15553570
TI  - Filling the cavities between children and oral health.

PMID- 15553571
TI  - Anti-vaccinationists and their impact on vaccination coverage in Wisconsin.

PMID- 15553572
TI  - Rickets in the Dairy State.
AB  - BACKGROUND: Nutritional vitamin D deficiency rickets occurs when children do not
      receive adequate vitamin D, which can be obtained from diet or manufactured in
      the skin when there is adequate sun exposure. A number of reports have described
      cases of vitamin D deficiency rickets in breastfed infants, but the public health
      significance of this problem in Wisconsin is unknown. OBJECTIVES: Our objectives
      were to identify cases of vitamin D deficiency rickets in Wisconsin infants and
      to determine the percentage of these infants participating in the Wisconsin
      Women, Infant and Children (WIC) program. METHODS: All cases of rickets due to
      nutritional vitamin D deficiency seen at Children's Hospital of Wisconsin or its
      associated outpatient clinics were identified by retrospective chart review. Data
      collected included date of birth, age at presentation, race, clinical
      presentation, diet history, history of vitamin supplementation, x-ray findings,
      and biochemical studies. The children with nutritional vitamin D deficiency
      rickets were cross-referenced with the Wisconsin WIC database. RESULTS: Fifty-one
      definite cases of nutritional vitamin D deficiency rickets were identified.
      Skeletal deformities, failure to thrive, fractures, seizures, incidental lab
      finding, tetany, and refusal to walk were the most common reasons for identifying
      rickets. All of the children were breastfed and did not receive vitamin
      supplementation. The infants had a mean age of 13.6 months and 46 (90%) were
      African American. Thirty-seven out of 51 children (73%) were enrolled in the
      Wisconsin WIC program. CONCLUSION: Vitamin D deficiency nutritional rickets is an
      important public health problem in Wisconsin. The Wisconsin WIC program may be an
      important site for intervention strategies.

PMID- 15553573
TI  - National survey of children with special health care needs: Wisconsin-specific
      data.
AB  - BACKGROUND: The National Center for Health Statistics developed and conducted
      (2000-2002) the National Survey of Children with Special Health Care Needs
      (CSHCN), a module of the State and Local Area Integrated Telephone Survey
      (SLAITS). OBJECTIVE: The purpose of this paper is to present the Wisconsin
      specific data derived from analysis of the national survey and to make a
      comparison with the United States as a whole. RESULTS: In Wisconsin,
      approximately one fifth (21%) of households have CSHCN, and 13.4% of children
      have a special health care need; US comparison data are 20% and 12.8%,
      respectively. When examined by type of special need, Wisconsin shows slightly
      higher proportions of CSHCN in all categories, when compared with U.S. data, with
      the exception of limitation in activity. Families in Wisconsin with CSHCN are
      more likely to report being involved with medical decision making and satisfied
      with services they receive (67%); having a medical home (57%); having adequate
      insurance; easy use of community-based service systems (81%); and receiving
      services to make transition to adult life (7.5%). CONCLUSION: Though Wisconsin
      has a slightly higher proportion of CSHCN than the United States as a whole, a
      greater proportion of Wisconsin families receive important services. These
      measurements allow us to strive for further improvement through coordination of
      services in the private health care delivery sector with public health programs.

PMID- 15553574
TI  - Excellent progress has been made but significant challenges remain.

PMID- 15553576
TI  - Improving rates of mammographic screening.

PMID- 15553577
TI  - Answering questions about leaders and leadership: a College priority.

PMID- 15553578
TI  - Can leadership make a difference?
AB  - Strong leadership is needed to reform the healthcare system in an accountable and
      transparent manner. This article examines the context of leadership development
      programs and the conditions that lead to their success as measured by effective
      outcomes. The article includes a discussion of evaluating leadership performance
      in the context of 360-degree feedback. In light of the current healthcare
      climate, caution should be exercised in implementing leadership training programs
      and the 360-degree process.

PMID- 15553579
TI  - Building a culture of ethics: the Capital Health Ethics Support model.
AB  - This article describes a new model for ethics support for Capital Health (a
      health region in Nova Scotia). With its emphasis on building a culture of ethics,
      many innovative elements are integral to this model and its future success.
      Particular emphasis is on organizational healthcare ethics and meaningful
      participation. Concerns about volunteer burden, urban and rural ethics needs, and
      varying exposure to prior ethics support will also be met by this model.

PMID- 15553580
TI  - A palette of desired leadership competencies: painting the picture for successful
      regionalization.
AB  - Regionalization is occurring across the country in an attempt to improve
      accessibility and services to populations with increased expectations and
      significant budget pressures. A successful reorganization requires strong and
      effective leadership, equipped with an array of knowledge, skills and abilities
      known as competencies. The model of leadership competencies presented in this
      article will become an essential tool for organizations in their pursuit of
      leaders to implement and drive successful change. This leadership competency
      model, discussed within a framework of change management process, will ensure
      that essential steps of change are followed and provide organizations with a
      blueprint for success. Is your organization ready?

PMID- 15553581
TI  - The costs of safeguarding privacy: one research organization's experience.
AB  - While academic health research has always observed strict vigilance in the
      guardianship of the rich information found in health databases, new legislation
      faced by all organizations ups the ante even higher. Research organizations like
      the Institute for Clinical Evaluative Sciences are delving into even more
      rigorous policies to keep sensitive information secure while preserving the value
      that dedicated research provides. The costs of implementing privacy protections
      are of great concern to Canadian researchers. This report discusses basic costs
      associated with privacy practices undertaken at the Institute.

PMID- 15553582
TI  - Building an effective risk management program in a healthcare setting.
AB  - This paper outlines a step-by-step approach to implementing an integrated risk
      management program in a healthcare setting. The paper argues for a corporate
      approach to risk management, based on centralized analysis of incidents and a
      focus on proactive management of risk factors. The paper discusses implementation
      from both structural and process perspectives and within the context of Canadian
      accreditation standards and the National Patient Safety Steering Committee
      recommendations.

PMID- 15553583
TI  - Essential skills for the future.

PMID- 15553585
TI  - Recent advances in glucosamine and chondroitin supplementation.
AB  - Glucosamine and chondroitin are alternative solutions to previous pharmaceutical
      options for the treatment of osteoarthritis. This article describes the
      mechanisms of action, pharmacokinetics, recent findings, and upcoming studies of
      these two natural remedies. The majority of studies on the mechanisms behind
      glucosamine and chondroitin have been performed in vitro or on animal models;
      however, the results have shown favorable effects on the balance between
      cartilage matrix synthesis and degradation. The pharmacokinetics of the three
      main forms of glucosamine were compared, and glucosamine hydrochloride displayed
      the greatest compound purity, despite the compounds having equal oral absorption
      rates of 90%. Chondroitin sulfate has been the principal clinical formulation
      with a slightly lower oral absorption of 70%. Clinical trials were evaluated
      based on two categories-radiographic changes and symptom improvement of pain and
      function. Although adverse effects of these two remedies were minor, the quality
      and labeled quantity of these relatively unregulated products must be considered.
      More randomized controlled studies on humans in vivo need to evaluate the
      efficacy, long-term effects, and quality of these compounds.

PMID- 15553586
TI  - Factors affecting postoperative range of motion after total knee arthroplasty.
AB  - One hundred thirty five patients with osteoarthritis who underwent total knee
      arthroplasty (TKA) were evaluated to determine whether specific pre- and
      postoperative variables were correlated with the postoperative range of motion.
      Age, sex, pre- and postoperative range of motion, pre- and postoperative Knee
      Society scores, intraoperative patellar thickness before and after resurfacing,
      pre- and postoperative radiographic patellar height (as determined by the Insall
      Salvati and Blackburn-Peel ratios), and preoperative radiographic alignment were
      recorded for each patient. Regression analysis was performed to identify whether
      any variables were correlated with the postoperative range of motion or Knee
      Society scores. The only variable that was significantly correlated with
      postoperative range of motion was the preoperative range of motion. This study
      suggests that among the variables evaluated, the preoperative range of motion was
      the only significant predictor of postoperative range of motion.

PMID- 15553587
TI  - Reliability of lower limb frontal plane alignment measurements using plain
      radiographs and digitized images.
AB  - This study evaluated the reliability of lower limb frontal plane alignment
      measures obtained from plain radiographs measured manually and digitized images
      measured using a custom computer software package (TheHTO Pro; Fowler Kennedy
      Sport Medicine Clinic, London, Ontario, Canada). Radiographic measurements used
      in the planning of high tibial osteotomy, including the mechanical axis angle and
      mechanical axis deviation, were measured on 42 hip-to-ankle radiographs on two
      separate occasions by two different raters (A.V.S., J.J.D.). Intraclass
      correlation coefficients (0.96-0.99) indicated excellent agreement between the
      manual and computer measurements, suggesting both methods can be used
      interchangeably. Although test-retest and inter-rater reliability tended to be
      slightly better when using TheHTO Pro, intraclass correlation coefficients were
      excellent for both methods (0.97-0.99). The standard errors of measurement were
      <1 degree for mechanical axis angle and <2 mm for mechanical axis deviation,
      regardless of method or rater. Based on the observed standard errors of
      measurement, conservative estimates for the error associated with an individual's
      mechanical axis angle at one point is approximately 1.5 degrees, and the minimal
      detectable change on reassessment is approximately 2 degrees. The error
      associated with an individual's mechanical axis deviation at one point is
      approximately 4 mm, and the minimal detectable change on reassessment is
      approximately 6 mm. These results suggest that manual and computer measurements
      of lower limb frontal plane alignment can be calculated with minimal measurement
      error. However, the small errors associated with both methods should be
      considered when making clinical decisions.

PMID- 15553588
TI  - Vascular risk associated with posterior cruciate ligament reconstruction using
      the arthroscopic transtibial tunnel technique.

PMID- 15553589
TI  - Genu recurvatum presenting as PCL insufficiency.

PMID- 15553590
TI  - Patient evaluation and surgical decision making.

PMID- 15553591
TI  - Cartilage restoration: overview of treatment options.

PMID- 15553592
TI  - The future of cartilage restoration.

PMID- 15553593
TI  - Food intake and gastrointestinal motility. A complex interplay.
AB  - The complex network between the central nervous system and the enteric nervous
      system plays a pivotal role in preparing the digestive tract to receive food,
      process it to activate digestion and control food intake itself. This field has
      always stimulated researchers and is now receiving notable impetus by the
      availability of sophisticated technologies able to provide an increasing amount
      of complex data. This article describes recent findings that underline the role
      of feeding and the gastrointestinal system in regulating food intake.

PMID- 15553594
TI  - Soluble adhesion molecules in healthy subjects: a dose-response study using n-3
      fatty acids.
AB  - BACKGROUND AND AIM: Long-chain n-3 polyunsaturated fatty acids (PUFA) may protect
      against atherosclerotic disease, and serum levels of soluble cellular adhesion
      molecules (sCAMs) possibly reflect the inflammatory process underlying
      atherosclerosis. We studied the effect of n-3 PUFA dietary supplementation on the
      serum levels of sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1)
      and soluble vascular adhesion molecule-1 (sVCAM-1), and the correlation between
      sCAMs and the fatty acid composition of granulocyte membranes. METHODS AND
      RESULTS: Sixty healthy volunteers were randomly assigned to receive a daily
      supplement of n-3 PUFA 6.6 g, n-3 PUFA 2.0 g, or olive oil for 12 weeks in a
      double blind design. A significant negative correlation was found between serum
      sICAM-1 levels and the DHA content of granulocyte membranes at entry. After
      supplementation with 6.6 g of n-3 PUFA, there was a significant decrease only in
      sP-selectin, which a gender subanalysis showed to be more marked in men. Among
      the women, there was a significant decrease in sICAM-1 in the PUFA 2.0 g group
      and a significant increase in sVCAM-1 in the PUFA 6.6 g group. CONCLUSIONS: The
      results indicate that high-dose supplementation with n-3 PUFA decreases sP
      selectin levels in healthy subjects, thus suggesting a decrease in platelet
      reactivity or endothelial activation. However, the effect of n-3 PUFA on sCAMs is
      complex and may depend on gender and n-3 PUFA dose.

PMID- 15553595
TI  - Prostaglandin E1 versus lumbar sympathectomy in the treatment of peripheral
      arterial occlusive disease: randomised study of 86 patients.
AB  - BACKGROUND AND AIM: The aim of this study was to compare the effects of a
      pharmacological and a surgical vasodilatatory therapy in the treatment of chronic
      arterial diseases of the lower limbs. METHODS AND RESULTS: After giving their
      informed consent, 40 patients were randomised to receive a slow (approximately 2
      hour) infusion of 40 microg of prostaglandin E1 twice daily for 28 days (group
      A), and 46 were randomised to undergo lumbar sympathectomy, including the second
      and third ganglion. Twenty-four (60%) of the patients in group A experienced
      complete remission, seven (17.5%) were partial responders, and nine (22.5%)
      failed to respond. Of the 46 patients in group B, 29 (63%) experienced complete
      remission, seven (15.2%) were partial responders, and 10 (21.7%) failed to
      respond. CONCLUSIONS: Broadly similar results were obtained with the two types of
      treatment, both of which are indicated mainly in Fontaine stages IIB and III (non
      advanced), particularly when revascularising therapy is impossible or excessively
      risky. The two strategies can be advantageously combined with direct
      revascularisation surgery and may therefore constitute a first-line approach
      favouring subsequent therapy.

PMID- 15553596
TI  - Apolipoprotein(a) size polymorphism is associated with coronary heart disease in
      polygenic hypercholesterolemia.
AB  - BACKGROUND AND AIM: In addition to high serum cholesterol levels, various
      cardiovascular risk factors may be involved in the development of coronary heart
      disease (CHD) in hypercholesterolemic subjects. As the levels of lipoprotein(a)
      [Lp(a)], an important and independent cardiovascular risk factor, are high in
      polygenic hypercholesterolemia (PH), we investigated plasma Lp(a) levels and
      apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of CHD events in
      PH patients. METHODS AND RESULTS: Lp(a) levels and apo(a) isoforms were
      determined in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94
      normocholesterolemic controls without CHD. Lp(a) levels were similar in the
      hypercholesterolemic subjects with (n=100) or without CHD (n=91): 21.4 (range 6.6
      59.23) vs 18.5 (range 5.25-57.25) mg/dL (p=NS). Low molecular weight apo(a)
      isoforms were more prevalent (55%) in the PH patients with CHD, whereas high
      molecular weight apo(a) isoforms were more prevalent (62.6%) in those without
      CHD: this difference was significant (p<0.05). A stepwise multiple-discriminant
      analysis made in order to determine the independence of common cardiovascular
      risk factors, Lp(a) levels and low molecular weight apo(a) isoforms in predicting
      CHD among hypercholesterolemic subjects showed that the presence of a positive
      family history of CHD, smoking, age, and the presence of at least one apo(a)
      isoform of low molecular weight were independently associated with CHD.
      CONCLUSIONS: Despite high Lp(a) levels, our findings do not support the
      hypothesis that Lp(a) plays an independent role in determining clinical CHD in PH
      subjects. However, the presence of at least one low molecular weight apo(a)
      isoform is an independent genetic predictor of CHD in hypercholesterolemic
      subjects. Together with other cardiovascular risk factors, apo(a) phenotypes
      should be assessed to evaluate the overall CHD risk status of all subjects with
      high serum cholesterol levels.

PMID- 15553597
TI  - Insulin sensitivity and hepatic steatosis in obese subjects with normal glucose
      tolerance.
AB  - BACKGROUND AND AIM: Hepatic steatosis has recently been associated with insulin
      resistance and other metabolic abnormalities as a possible feature of the
      metabolic syndrome, but it is still uncertain how hepatic steatosis and insulin
      sensitivity are connected. Furthermore, obesity is a well characterized insulin
      resistant condition that is often associated with hepatic steatosis. The aim of
      this study was to verify whether hepatic steatosis further worsens insulin
      sensitivity in obese subjects by comparing the degree of insulin sensitivity in
      obese subjects with normal glucose tolerance on the basis of the presence or
      absence of hepatic steatosis. METHODS AND RESULTS: We analyzed 86 obese patients
      whose alcohol intake was less than 20 g/day and who showed no signs of viral
      hepatopathy. All of the subjects had normal glucose tolerance as shown by an oral
      glucose tolerance test. Insulin resistance was estimated using the homeostasis
      model assessment (HOMA) method and the diagnosis of steatosis was determined by
      an ultrasound scan of the liver. The subjects were comparable in terms of body
      mass index (BMI), lipid profile and serum uric acid levels; those with hepatic
      steatosis were slightly older and tended to have higher systolic blood pressure
      and fasting glycemia levels. The HOMA values were significantly higher in the
      group with hepatic steatosis (4.48 +/- 2.22 vs 3.11 +/- 1.47, p=0.002). There was
      no linear correlation between HOMA and alanine aminotransferase (ALT) levels, but
      a close linear correlation between HOMA and BMI (r=0.40; p<0.001). The effect of
      hepatic steatosis on HOMA remained significant after adjusting for age and gender
      (covariance analysis, p=0.006). When BMI was added to the covariance analysis,
      hepatic steatosis retained its statistical significance. CONCLUSION: Our data
      suggest that hepatic steatosis can increase insulin resistance independently of
      obesity.

PMID- 15553598
TI  - Pair-wise detection of eight common DNA polymorphisms of the human lipoprotein
      lipase gene by PCR-RFLP. Findings of the Olivetti Heart Study.
AB  - We developed a rapid procedure to analyse simultaneously two different DNA
      polymorphisms of the human LPL gene by PCR-RFLP (Polymerase Chain Reaction
      Restriction Fragment Length Polymorphism). The method involves PCR amplification
      of the gene fragments encompassing two polymorphic sites, direct digestion in the
      same PCR-tube of the amplification mixture with two restriction enzymes, and the
      analysis of the resulting DNA fragments by gel electrophoresis. In 422
      participants of the 1994 follow-up examination of the Olivetti Heart Study, a
      total of eight common LPL gene polymorphisms have been analysed in pairs by this
      procedure: -93 T/G and D9N; V108V and T361T; N291S and PvuII; HindIII and S447X.
      Two of these polymorphisms (V108V and T361T) were analysed for the first time.
      This method is suitable for the routine analysis of clinical samples of varying
      DNA content and practically halves the times and costs of screening for these LPL
      polymorphisms.

PMID- 15553599
TI  - Effects of cholesterol supplementation on antioxidant enzyme activities in rat
      hepatic tissues: possible implications of hepatic paraoxonase in atherogenesis.
AB  - BACKGROUND AND AIM: The effects of cholesterol supplementation on antioxidant
      enzyme activities were investigated hepatic tissue taken from Sprague Dawley
      rats. METHODS AND REULTS: The study involved 14 male Sprague Dawley rats: seven
      fed a normal laboratory diet and seven a normal diet plus cholesterol (3.6
      g/kg/day) for three months, during which blood samples were obtained to measure
      serum cholesterol levels. At the end of the 3-month period, the livers were
      surgically removed in order to measure antioxidant enzyme activities (superoxide
      dismutase, catalase, glutathione peroxidase and paraoxonase-1). At the end of the
      study period, serum total cholesterol and HDL-cholesterol levels were
      significantly higher in the cholesterol-fed group than the control group. There
      were no significant between-group differences in hepatic superoxide dismutase,
      catalase and glutathione peroxidase activities, but there was a significant
      decrease in hepatic paraoxonase-1 activity in the cholesterol-fed group.
      CONCLUSIONS: Cholesterol supplementation significantly decreases paraoxonase-1
      activity in rat liver tissue without changing the activities of other antioxidant
      enzymes. These results suggest that cholesterol significantly suppresses hepatic
      paraoxonase-1 synthesis. It seems that the decreased paraoxinase-1 activity in
      the plasma HDL-fraction of atherosclerotic patients is associated with suppressed
      liver synthesis. A reduction in paraoxonase-1 activity may therefore lead to the
      more intensive exposure of LDL to oxidant attacks.

PMID- 15553600
TI  - Prescription of statins to dyslipidemic patients affected by liver diseases: a
      subtle balance between risks and benefits.
AB  - AIM: Statins reduce cardiovascular morbidity and mortality in the general
      population with an excellent risk-benefit profile. The most frequent adverse
      events are myopathy and increase in hepatic aminotransferases. In this review, we
      consider the role of liver in metabolism of statins, their potential hepatic
      toxicity and the guidelines for their prescription in patients affected by
      different liver diseases. DATA SYNTHESIS: Statin-induced hepatic toxicity: i)
      occurs in 1-3% of patients; ii) is characterized by increased aminotransferase
      levels; iii) is dose-related; iv) is frequently asymptomatic; v) usually reverts
      after dosage reduction or treatment withdrawal. Finally, after recovery, a
      rechallenge with the same or other statins may not result in increased
      aminotranferases. CONCLUSIONS: Caution is needed when prescribing statins to
      patients with liver disease, and liver toxicity should always be monitored during
      statin treatment. In particular, i) the potential hepatic toxicity requires
      frequent control of biochemical parameters related to hepatic cytolysis and
      cholestasis in all patients on statins; ii) administration of statins is
      counterindicated in patients with advanced or end-stage parenchymal liver disease
      due to the relevant impairment of their metabolism; iii) cholestatic disorders
      with secondary dyslipidemia do not require statin treatment even if relevant
      alterations of the lipid pattern are detected; iv) patients with acute liver
      disease of viral or alcoholic etiology should not receive statins until
      normalization of cytolysis enzymes; v) chronic hepatitis patients may be treated
      by statins if their cardiovascular risk is elevated and provided that careful
      follow-up is carried out to rapidly recognize the onset of further liver damage;
      vi) liver transplantation recipients affected by dyslipidemia induced by
      immunosuppressive therapy can be treated with statins under careful clinical
      control; vii) the benefits of statins should likely overcome the risks in the
      large majority of dyslipidemic patients affected by non-alcoholic
      hepatosteatosis, a disease frequently diagnosed in insulin-resistant subjects.

PMID- 15553601
TI  - A case of Buerger's disease associated with MTHFR C677T mutation homozygosity: a
      possible therapeutic support.

PMID- 15553602
TI  - The allergenic specificities of the house dust mite.
AB  - The most important house dust mites are Dermatophagoides pteronyssinus and in
      drier areas D. farinae. In subtropical and tropical regions the glycyphagid mite
      Blomia tropicalis is a major source of allergen, which co-exists with D.
      pteronyssinus. The group 1 and 2 allergens of Dermatophagoides mites are clearly
      major specificities and it is likely that these allergens could be the basis of
      new strategies of immunotherapy for many mite-allergic subjects. About 20% of
      patients, however, do not have IgE antibody to the group 1 and 2 allergens, and
      even though this is a minority, it constitutes a large population. There are also
      many other house dust mite allergens which have high IgE binding activity but
      these are present in low and variable concentrations in mite extracts, usually at
      less than 1% of the group 1 and 2 allergens. It must be appreciated that mite
      extracts are arbitrary preparations that do not accurately represent the relative
      concentrations of allergens in inhaled air. There is now the opportunity to
      produce more representative and more balanced formulations of allergens, possibly
      by mixtures of recombinant allergens. It is likely that the group 3, 5, 7 and 9
      allergens will be important along with the high molecular weight group 11, 14, 15
      and 18. The tropomyosin group 10 may be an important cross-reacting allergen. B.
      tropicalis is, because of its distribution in highly populated regions with
      increasing affluence, a very important allergen. It has low-grade cross
      reactivity with Dermatophagoides but most allergens only have 30-40% sequence
      identity between the different families so they require different allergens for
      immunotherapy and new diagnostic measures are required to distinguish the
      sensitivity between the mite families. Studies on B. tropicalis allergens are
      required to identify the major allergens that do not appear to be the group land
      2 specificities. Component resolved diagnosis is a newly developing procedure
      that uses allergen arrays to provide a diagnostic format to differentiate between
      cross-reacting allergens and to identify the optimal formulation of allergens for
      different patients.

PMID- 15553603
TI  - Treatment of recurrent ovarian cancer.
AB  - Recurrent ovarian cancer is a common clinical problem and the management of each
      patient must be individualized. Diagnosis is usually based on a progressively
      rising CA-125 titre, and a CT scan of the pelvis and abdomen, together with a
      chest X-ray should be performed in this situation. Although there is no study to
      support immediate treatment in the asymptomatic patient, our approach is to
      commence such patients on Tamoxifen. Chemotherapy is reserved for symptomatic
      patients or those who progress on Tamoxifen. The choice of non-platinum second or
      subsequent line chemotherapy is based on many factors including likelihood of
      benefit, potential toxicity, schedule and convenience to the patient, as well as
      organ function and residual toxicity from prior treatment. Aggressive secondary
      cytoreductive surgery can significantly prolong survival in those with a disease
      free interval of 24 months or more, and in those in whom all macroscopic disease
      can be removed. Radiation therapy to the tumour bed following resection of
      localized disease may be beneficial in selected patients. Quality of life issues
      are particularly important for this group of patients and have not been
      adequately studied. Communication regarding the objectives of therapy is
      important, and the multidisciplinary approach should include palliative care and
      psycho-social support, in addition to the more traditional medical options.

PMID- 15553604
TI  - Comparing cruciate-retaining total knee arthroplasty and cruciate-substituting
      total knee arthroplasty: a prospective clinical study.
AB  - BACKGROUND: This prospective clinical study was performed to compare the clinical
      outcomes and radiographic changes between patients with cruciate-retaining (CR)
      and cruciate-substituting (CS) total knee arthroplasty (TKA). METHODS: From 1997
      through 1998, 228 patients (183 females and 45 males) with a total of 267 knees
      with an average age of 55 years (range, 20 to 83 years) were enrolled in this
      study. Patients were randomly divided into two groups including group I of 137
      patients underwent 157 CR TKA, and group II of 91 patients underwent 110 CS total
      knee arthroplasties. The evaluation parameters included knee scores, functional
      scores, radiographs of the knees and SF-12 surveys. The average follow-up period
      was 42 months (range, 24 to 66 months). RESULTS: The overall results for group I
      were 74.3% excellent, 17.7% good, 7.1% fair and 0.9% poor for; and 76.9%
      excellent, 19.2% good and 3.8% fair for group II. No significant differences were
      noted in the overall results between the two groups. The radiographic changes
      showed no discernable differences. CONCLUSIONS: Cruciate-retaining and cruciate
      substituting total knee arthroplasties function equally well at 2 to 5 years
      postoperatively. The ultimate differences between the patients who underwent CR
      TKA and CS TKA need to be examined after long-term follow up.

PMID- 15553605
TI  - Vascular abnormalities in the head and neck area in velocardiofacial syndrome.
AB  - BACKGROUND: Velocardiofacial syndrome (VCFS) is a disorder commonly associated
      with a characteristic facial appearance, congenital heart disease, and
      velopharyngeal insufficiency. An association with vascular anomalies in the
      cervical area and skull base has been reported. In this study, we evaluated 7
      consecutive patients who received vascular imaging for preoperative planning of
      velopharyngeal surgery. METHODS: From January 1996 to September 1997, 7 patients
      with VCFS were found in 1 of the senior author's service. All had documented
      velopharyngeal insufficiency and visible pulsations over the posterior pharyngeal
      wall by nasoendoscopy. Two patients had magnetic resonance angiography (MRA), 2
      patients had computed tomographic angiography (CTA), and 3 patients had both.
      RESULTS: The angiographic study revealed abnormalities of the carotid and
      vertebral arteries in 5 patients (71%). Kinking and tortuosity of the internal
      carotid artery and its medial displacement were common. The observed pulsations
      did not correlate well with the angiographic findings. For surgical correction of
      the velopharyngeal sufficiency, a regular pharyngeal flap was used in 4 patients,
      a modified pharyngeal flap was used in 2 patients, and the surgery was abandoned
      in the remaining 1 patient. CONCLUSIONS: Expression of cervical vascular
      anomalies in VCFS was varied and did not correlate well with the observed
      pulsations from the nasopharyngoscopic examination. Preoperative vascular imaging
      study is essential for the purpose of planning and safety of surgical
      interventions in this area.

PMID- 15553606
TI  - A comparison of urodynamic parameters and lower urinary tract symptoms in
      urodynamic genuine stress incontinence women with or without stress urinary
      incontinence.
AB  - BACKGROUND: The aim of this study was to investigate the urodynamic parameters
      and lower urinary tract symptoms (LUTS) of women with urodynamic genuine stress
      incontinence (GSI). METHODS: A cross-sectional study involving 3323 women with
      LUTS was conducted. We recruited 1261 women with urodynamic GSI and were further
      grouped as with or without symptomatic stress urinary incontinence (SUI). The
      LUTS and urodynamic measurements between the two groups were analyzed and
      compared. RESULTS: Women with symptomatic SUI had a greater maximal flow rate,
      larger voided volume, larger maximal cystometric capacity, and smaller maximal
      urethral closure pressure (MUCP) during both rest and stress. The amount of urine
      leakage during the 1-hour pad test of GSI women with symptomatic SUI was much
      greater than women without symptomatic SUI (26.0 g vs 7.2 g, p < 0.001). The
      significant differences in other lower urinary tract symptoms including nocturia,
      diurnal frequency, incomplete emptying, poor stream, urgency, urge incontinence,
      and post-void dribbling in women without symptomatic SUI were all less than women
      with symptomatic SUI. CONCLUSIONS: The urodynamic parameters and LUTS between the
      GSI women with or without symptomatic SUI are different. Approximate 15% of the
      GSI women do not complain of symptomatic SUI. The lower urinary tract symptoms of
      women with GSI without symptomatic SUI were less prominent than for the GSI women
      with symptomatic SUI.

PMID- 15553607
TI  - Surgical results of persistent fetal vasculature.
AB  - BACKGROUND: To evaluate the surgical results of patients with persistent fetal
      vasculature (PFV), also known as persistent hyperplastic primary vitreous (PHPV).
      METHODS: From 1991 to 2001, a retrospective, noncomparative study of 7 eyes of 7
      patients diagnosed with PFV was conducted. In each case, type of anterior and/or
      posterior PHPV findings, preoperative testing, surgical procedures, and visual
      outcomes were obtained from the records. Follow-up ranged from 12 to 43 months,
      with a mean of 15 months. RESULTS: Of the 7 eyes, one (14%) had strictly anterior
      PFV, 1 (14%) had strictly posterior PFV, and 5 (71%) had components of both
      anterior and posterior disease. Initial lens aspiration only was performed in 3
      (43%) eyes. Initial vitrectomy only was performed in 1 eye (14%). Initial
      lensectomy and vitrectomy was performed in 3 (42.8%) eyes. The reoperation rate
      was 43% for membrane reproliferation, glaucoma, vitreous hemorrhage, and retinal
      detachment. Final best-corrected visual acuity ranged from light perception only
      to 20/70 on the Snellen chart. CONCLUSIONS: Functional vision is possible in
      selected patients. However, poor final visual outcome despite adequate anatomic
      success were noted in this study. The poor outcomes might have been due to
      patients delaying vitrectomy until retinal detachment developed or that the
      patients had poor compliance with postoperative ocular rehabilitation.

PMID- 15553608
TI  - Efficacy and safety of phacoemulsification with intraocular lens implantation
      under topical anesthesia.
AB  - BACKGROUND: To eliminate complications of peribulbar and retrobulbar anesthesia
      and to achieve efficacy and safety for topical anesthesia with cataract surgery.
      METHODS: We performed clear corneal phacoemulsification with foldable intraocular
      lens (IOL) implantation under topical anesthesia using preservative-free 2%
      lidocaine drops, without intracameral anesthetic supplementation. The exclusion
      criteria were anxiety, small pupil, baseline endothelial count 1500 cells/mm2,
      uncontrolled glaucoma, other ocular entities affecting corneal endothelium, and
      allergy to the relevant medications. We used a specular microscope to evaluate
      the effect on the endothelium and employed a 10-point visual analog pain scale to
      assess the discomfort experienced during the operation. RESULTS: Totally, 29 eyes
      of 29 patients were enrolled in this series. The mean age was 71.5 +/- 8.5 years.
      Twenty-three of 29 (79.3%) cases achieved a best-corrected visual acuity (BCVA)
      equal to 20/40 or better at an interval of 3 months postoperatively. Most
      patients (86.5%) felt mild or no pain during surgery. Pre- and postoperative
      endothelial counts were 2072.6 +/- 104 and 1927.4 +/- 196 cell/mm2, respectively.
      One in 29 cases developed vitreous loss due to involuntary eye movements
      intraoperatively. CONCLUSIONS: Topical anesthesia with preservative-free 2%
      lidocaine drops is an effective and safe modality for clear corneal
      phacoemulsification with IOL implantation. On the other hand, for patients with
      small pupil or those who are anxious, the procedure may be time-consuming, and it
      is challenging for physicians to perform cataract surgery merely using topical
      anesthesia.

PMID- 15553609
TI  - Pseudoaneurysm formation 12 years after ringed intraluminal graft replacement for
      type B aortic dissection.
AB  - A sutureless ringed intraluminal graft has been used as a substitute for the
      diseased aorta with the advantage of decreasing the aortic cross-clamp time and
      blood loss. Concerns remain about implications of anecdotal accounts of late
      complications with this graft. We report on the experience of a 68-year-old man,
      successfully treated for type B aortic dissection using the sutureless technique,
      who developed a pseudoaneurysm and aortobronchial fistula over the distal
      anastomosis of the intraluminal graft 12 years after the operation.

PMID- 15553610
TI  - Radiofrequency ablation: an alternative treatment method of renal cell carcinoma.
AB  - Renal Cell Carcinoma (RCC) is a common renal parenchymal malignancy. Although
      complete or partial nephrectomy is still the gold standard of management, a lot
      of minimally invasive techniques are currently emerging into the field of
      treatment. Recently, image-guided radiofrequency (RF) ablation has received
      increasing attention and been proposed as an alternation to more invasive
      procedures such as partial or radical nephrectomy. For the RCC patients who are
      not amenable to surgery or have a single kidney, RF ablation is another feasible
      option of management. We present a 71-year-old patient who had right nephrectomy
      for RCC 10 years prior to admission, and hypertension and arrhythmia under
      regular treatment. He was noted to have two masses in the left kidney and right
      adrenal gland, respectively, on follow-up computed tomography images.
      Percutaneous biopsies of the left renal and right adrenal masses were proven to
      be renal cell carcinoma. After a right adrenalectomy was performed, this patient
      underwent two treatment sessions of percutaneous RF ablation to avoid a
      nephrectomy which would lead her on dialysis. Successful treatment was impressed
      after 1 year of follow-up. We report this case to emphasize the potential role of
      percutaneous RF ablation on the treatment of RCC.

PMID- 15553611
TI  - Postpartum unilateral Horner's syndrome following lumbar epidural anesthesia
      after a Cesarean delivery.
AB  - We report on a case demonstrating unilateral Horner's syndrome (HS) after lumbar
      epidural obstetric anesthesia. A healthy, 32-year-old woman with a breech
      presentation was scheduled for an elective Cesarean section. The patient had
      normal vital signs throughout the surgical procedure. The operation lasted for 50
      min. In the recovery room, she complained of left nasal stuffiness, left cheek
      numbness, and heaviness in her left eye. Meanwhile, left nipple sensory loss was
      noted during baby suckling training. On physical examination, her left eyelid was
      droopy along with left-side ptosis and facial flushing. Reduced sensation over
      the left hemifacial region and upper arm was also noted, which resolved
      completely over the next 110 min. A diagnosis of unilateral HS was then made.
      Although typically a benign side effect which often spontaneously resolves, HS is
      likely to cause anxiety in both the patient and the doctor. Prompt recognition of
      this syndrome and determination of its cause from lumbar epidural anesthesia can
      prevent unnecessary and potentially dangerous diagnostic workup and can reassure
      both patients and clinicians. The patient was discharged from the hospital 5 days
      after onset with a good outcome.

PMID- 15553612
TI  - Sudden hearing loss as the initial manifestation of chronic myeloid leukemia in a
      child.
AB  - Hearing loss and blindness rarely occur in patients with chronic myeloid leukemia
      (CML). In this article, we present a 12-year-old girl who had right-side hearing
      loss as the initial manifestation of CML, followed by left-side hearing loss and
      blindness of the left eye several days after initiating treatment. The initial
      white cell count was 181,700/mm3. Audiometry showed severe sensorineural hearing
      loss of her right ear and moderate mixed hearing loss of the left ear. An
      ophthalmic examination showed optic neuropathy with subhyaloid hemorrhage in the
      left eye. A brain magnetic resonance image showed minor hemorrhaging in the right
      lower frontal area and anterior thalamus. These findings might have implied
      leukostasis with hyperviscosity syndrome. She died on the 9th hospital day. This
      case illustrates that CML should be considered 1 of the rare diagnoses in a
      patient with sudden onset of hearing loss.

PMID- 15553613
TI  - "Public health consequences of macrolide use in food animals: a deterministic
      risk assessment," a comment on: J. Food Prot. 67(5):980-992 (2004).

PMID- 15553614
TI  - "Public health consequences of macrolide use in food animals: a deterministic
      risk assessment," a comment on: J. Food Prot. 67(5):980-992 (2004).

PMID- 15553615
TI  - Efficacy of sanitizers to inactivate Escherichia coli O157:H7 on fresh-cut carrot
      shreds under simulated process water conditions.
AB  - Chlorine is widely used as a sanitizer to maintain the microbial quality and
      safety of fresh-cut produce; however, chlorine treatment lacks efficacy on
      pathogen reduction, especially when the fresh-cut processing water contains heavy
      organic loads. A more efficacious sanitizer that can tolerate the commercial
      processing conditions is needed to maintain microbial safety of fresh-cut
      produce. This study evaluated the efficacy of Escherichia coli O157:H7 reduction
      on fresh-cut carrots using new and traditional sanitizers with tap water and
      fresh-cut processing water scenarios. Fresh-cut carrot shreds inoculated with E.
      coli O157:H7 were washed in sanitizer solutions including 200 ppm chlorine,
      citric acid-based sanitizer (Pro-San), 80 ppm peroxyacetic acid-based sanitizer
      (Tsunami 100), and 1,000 ppm acidified sodium chlorite (SANOVA) prepared in fresh
      tap water or simulated processing water with a chemical oxygen demand level of
      approximately 3,500 mg/liter. Samples were packaged and stored at 5 degrees C.
      Microbial analyses performed at days 0, 7, and 14 indicate that the organic load
      in the process water significantly affected the efficacy of chlorine on pathogen
      removal and was especially evident on samples tested during storage. Acidified
      sodium chlorite provided a strong pathogen reduction even under process water
      conditions with up to a 5.25-log reduction when compared with the no-wash
      control. E. coli O157:H7 was not recovered on acidified sodium chlorite-treated
      samples during the entire 14 days of storage, even following an enrichment step.
      These results suggest that acidified sodium chlorite holds considerable promise
      as an alternative sanitizer of fresh-cut produce.

PMID- 15553616
TI  - Survival of Escherichia coli O157:H7 and Salmonella in apple cider and orange
      juice as affected by ozone and treatment temperature.
AB  - Inactivation of Escherichia coli O157:H7 and Salmonella in apple cider and orange
      juice treated with ozone was evaluated. A five-strain mixture of E. coli O157:H7
      or a five-serovar mixture of Salmonella was inoculated (7 log CFU/ml) into apple
      cider and orange juice. Ozone (0.9 g/h) was pumped into juices maintained at 4
      degrees C, ambient temperature (approximately 20 degrees C), and 50 degrees C for
      up to 240 min, depending on organism, juice, and treatment temperature. Samples
      were withdrawn, diluted in 0.1% peptone water, and surface plated onto recovery
      media. Recovery of E. coli O157:H7 was compared on tryptic soy agar (TSA),
      sorbitol MacConkey agar, hemorrhagic coli agar, and modified eosin methylene blue
      agar; recovery of Salmonella was compared on TSA, bismuth sulfite agar, and
      xylose lysine tergitol 4 (XLT4) agar. After treatment at 50 degrees C, E. coli
      O157:H7 populations were undetectable (limit of 1.0 log CFU/ml; a minimum 6.0-log
      CFU/ml reduction) after 45 min in apple cider and 75 min in orange juice. At 50
      degrees C, Salmonella was reduced by 4.8 log CFU/ml (apple cider) and was
      undetectable in orange juice after 15 min. E. coli O157:H7 at 4 degrees C was
      reduced by 4.8 log CFU/ml in apple cider and by 5.4 log CFU/ml in orange juice.
      Salmonella was reduced by 4.5 log CFU/ml (apple cider) and 4.2 log CFU/ml (orange
      juice) at 4 degrees C. Treatment at ambient temperature resulted in population
      reductions of less than 5.0 log CFU/ml. Recovery of E. coli O157:H7 and
      Salmonella on selective media was substantially lower than recovery on TSA,
      indicating development of sublethal injury. Ozone treatment of apple cider and
      orange juice at 4 degrees C or in combination with mild heating (50 degrees C)
      may provide an alternative to thermal pasteurization for reduction of E. coli
      O157:H7 and Salmonella in apple cider and orange juice.

PMID- 15553617
TI  - Occurrence of Escherichia coli, noroviruses, and F-specific coliphages in fresh
      market-ready produce.
AB  - Forty samples of fresh produce collected from retail food establishments were
      examined to determine the occurrence of Escherichia coli, F-specific coliphages,
      and noroviruses. An additional six samples were collected from a restaurant
      undergoing investigation for a norovirus outbreak. Nineteen (48%) of the retail
      samples and all outbreak samples were preprocessed (cut, shredded, chopped, or
      peeled) at or before the point of purchase. Reverse transcription-PCR, with the
      use of primers JV 12 and JV 13, failed to detect norovirus RNA in any of the
      samples. All six outbreak samples and 13 (33%) retail samples were positive for F
      specific coliphages (odds ratio undefined, P = 0.003). Processed retail samples
      appeared more likely to contain F-specific coliphages than unprocessed samples
      (odds ratio 3.8; 95% confidence interval 0.8 to 20.0). Only two (5.0%) retail
      samples were positive for E. coli; outbreak samples were not tested for E. coli.
      The results of this preliminary survey suggest that F-specific coliphages could
      be useful conservative indicators of fecal contamination of produce and its
      associated virological risks. Large-scale surveys should be conducted to confirm
      these findings.

PMID- 15553618
TI  - Escherichia coli O157:H7 in a cohort of weaned, preconditioned range beef calves.
AB  - Escherichia coli O157:H7 (EC O157) is an important cause of foodborne disease.
      Cattle are reservoirs for the bacteria and are implicated in transmission to
      humans. Prevalence data in prefeedlot calves are limited. With the use of
      sensitive methods, a cohort of weaned beef calves (n = 408) was sampled before
      and after preconditioning to estimate fecal point prevalence and describe changes
      in EC O157 fecal shedding. EC O157 isolates were confirmed and characterized by
      PCR and pulsed-field gel electrophoresis. Calves from 29 cow-calf farms were
      commingled at three preconditioning sites and placed on a transition ration
      containing oxytetracycline (200 g/ton) for 45 days. Initial animal-level fecal
      point prevalence was 2.5% (95% confidence interval, 1 to 5) with a herd-level
      prevalence of 17.2% (95% confidence interval, 6 to 36). Point prevalence
      following the preconditioning feeding period was 0%. An unexpected finding in our
      study was EC O157 isolates that were Shiga toxin-deficient. Pulsed-field gel
      electrophoresis subtypes of EC O157 were unique in epidemiologically unlinked
      herds, except one herd that had two unique subtypes. We expected, but observed,
      neither increased fecal shedding in the cohort nor horizontal transmission of
      unique EC O157 subtypes. The absence of fecal shedding following the 45-day
      feeding period might be attributable to seasonal influences, inhibitory
      concentrations of oxytetracycline in the transition ration, or transient
      colonization that ended before sampling. EC O157 is apparently widely dispersed
      at low prevalence in U.S. prefeedlot, weaned calves.

PMID- 15553619
TI  - Spread of marker bacteria from the hides of cattle in a simulated livestock
      market and at an abattoir.
AB  - The spread of microbial contamination on the hides of beef was investigated at
      two stages in the meat chain: (i) in a simulated livestock market ("the market")
      using 33 animals, and (ii) in the unloading-to-skinning area of a commercial
      abattoir using 18 animals. At both stages, harmless bacterial markers (nalidixic
      acid-resistant Escherichia coli K-12; rifampicin- and nalidixic acid-resistant
      Pseudomonas fluorescens; and a tetracycline-resistant E. coli) were inoculated on
      the hides of a small number of selected animals, and their transfer to other
      animals and the environment was examined. At the market, the initial prevalence
      of animals positive for the hide markers (9.1% in each phase) introduced in the
      presale pen, sale ring, and postsale pen changed to 39.4, 15.1, and 54.5%,
      respectively, by the end of the market process. In addition, widespread
      contamination of the market environment with the hide markers was observed. At
      the abattoir, the initial prevalence of animals positive for the hide marker
      (11.1%) inoculated at unloading increased to 100% (hide before skinning) and
      88.8% (skinned carcass). In addition, another marker inoculated on environmental
      surfaces in lairage pens, races, and stunning box was detected on 83.3% (hide
      before skinning) and 88.8% (skinned carcass). These results, although obtained
      with a relatively small number of animals, demonstrate that both the livestock
      market process and the unloading-to-skinning process at abattoirs can facilitate
      the extensive spread of microbial contamination on hides not just within, but
      also between, batches of animals.

PMID- 15553620
TI  - A mathematical model for the transmission of Salmonella Typhimurium within a
      grower-finisher pig herd in Great Britain.
AB  - In a study of pigs slaughtered at British abattoirs, approximately 23% carried
      Salmonella in their cecal (large intestine) contents. The most frequent serotype
      was Salmonella Typhimurium (STM), which was the second most common cause of human
      salmonellosis in Great Britain. A pig industry-monitoring program was developed
      to reduce Salmonella infection on British farms. The control of STM infection on
      the farm requires an understanding of STM transmission dynamics within the herd,
      and a mathematical model has been developed for an infected grower-finisher farm.
      The model estimates the probability of a random pig being infected with STM.
      There are three broad categories of STM infection in pigs: pigs that are infected
      but unable to transmit the infection (latent); pigs that are infectious, i.e.,
      able to transmit the infection (shedders); and pigs that have stopped shedding
      but harbor STM in their internal organs (carriers). The model estimates that
      21.0% (5th and 95th percentiles, 0.05 to 77.5%) of slaughter-age pigs on an
      infected farm are likely to be shedding STM. Although this range is wide, it is
      biologically plausible. Sensitivity analysis of the total number of infected pigs
      revealed that the most significant input parameters are the probability of
      effective contact between a specific infectious and susceptible pig and the
      duration of shedding. The model predicted that 11.5% of pigs would be shedding
      STM at slaughter age. This value is close to the estimate obtained from a British
      abattoir survey that 11. 1% of pigs carried STM in their ceca, indicating that
      the model has reasonable validity.

PMID- 15553621
TI  - Juice irradiation with Taylor-Couette flow: UV inactivation of Escherichia coli.
AB  - A novel reactor is described with flow characteristics that approach that of
      ideal plug flow but with a residence time that is uncoupled from the
      hydrodynamics or boundary layer characteristics. The design described consists of
      an inner cylinder that rotates within a stationary but larger outer cylinder. At
      low rotation rates, a laminar, hydrodynamic configuration called Taylor-Couette
      flow is established, which consists of a system of circumferential vortices
      within the annular fluid gap. The latter constitutes a spatially periodic flow
      that is the hydrodynamic equivalent to cross flow over a tube bank or lamp array.
      These vortices provide radial mixing, reduce the boundary layer thickness, and
      are independent of the axial flow rate and thus the fluid residence time. An
      additional feature of the rotating design is the repetitive exposure of the fluid
      parcels to a minimum number of lamps, which substantially reduces the maintenance
      requirements. Inactivation data for Escherichia coli (ATCC 15597) were recorded
      in commercial apple and grape juice that are relatively opaque to UV radiation.
      With initial E. coli concentrations of approximately 10(6) CFU/ml, Taylor-Couette
      flow was found to provide a 3- to 5-log improvement in the inactivation
      efficiency compared with simple channel flow between concentric cylinders.

PMID- 15553622
TI  - Egg consumption patterns and Salmonella risk in Finland.
AB  - To estimate the consumer risk of contracting Salmonella infection via shell eggs
      and to evaluate the effect of possible preventative measures, quantitative
      microbiological risk assessment is being developed in Finland. As a part of the
      risk assessment, a survey of 918 respondents was conducted to study how
      households purchase, store, handle, and use eggs. In addition, suitability of the
      Internet as a survey method was compared with a postal survey. Shell eggs were
      usually purchased once every 2 weeks (41% of all the respondents). Ninety-one
      percent of the respondents bought eggs in groceries and 93% stored eggs at
      chilled temperatures. The majority of the respondents (80%) only had eggs in
      their home for which the best-before date had not expired. Only 34% of the
      respondents said that they always washed their hands after breaking eggs.
      Consumption of well-cooked eggs accounted for 84%, consumption of soft-boiled
      eggs for 12%, and consumption of raw eggs for 4% of the total amount of eggs
      consumed. The elderly used eggs more frequently than the whole population, but
      the consumption of raw egg dishes decreased with age. The Internet survey was a
      rapid method for transmitting information, but its response rate was low (9%),
      and it did not appear to be a suitable tool for data collection in a general
      population. The results indicate that although the majority of the respondents
      had safe egg-handling practices, a substantial minority of the consumers had risk
      prone behavior.

PMID- 15553623
TI  - Real-time PCR quantification of Vibrio parahaemolyticus in oysters using an
      alternative matrix.
AB  - This study examined the relationship between levels of total Vibrio
      parahaemolyticus found in oyster tissues and mantle fluid with the goal of using
      mantle fluid as a template matrix in a new quantitative real-time PCR assay
      targeting the thermolabile hemolysin (tlh) gene for the enumeration of total V.
      parahaemolyticus in oysters. Oysters were collected near Mobile Bay, Ala., in
      June, July, and September and tested immediately after collection and storage at
      26 degrees C for 24 h. Initial experiments using DNA colony hybridization
      targeting tlh demonstrated that natural V. parahaemolyticus levels in the mantle
      fluid of individual oysters were strongly correlated (r = 0.85, P < 0.05) with
      the levels found in their tissues. When known quantities of cultured V.
      parahaemolyticus cells were added to real-time PCR reactions that contained
      mantle fluid and oyster tissue matrices separately pooled from multiple oysters,
      a strong linear correlation was observed between the real-time PCR cycle
      threshold and the log concentration of cells inoculated into each PCR reaction
      (mantle fluid: r = 0.98, P < 0.05; and oyster: r = 0.99, P < 0.05). However, the
      mantle fluid exhibited less inhibition of the PCR amplification than the
      homogenized oyster tissue. Analysis of natural V. parahaemolyticus populations in
      mantle fluids using both colony hybridization and real-time PCR demonstrated a
      significant (P < 0.05) but reduced correlation (r = -0.48) between the two
      methods. Reductions in the efficiency of the real-time PCR that resulted from low
      population densities of V. parahaemolyticus and PCR inhibitors present in the
      mantle fluid of some oysters (with significant oyster-to-oyster variation)
      contributed to the reduction in correlation between the methods that was observed
      when testing natural V. parahaemolyticus populations. The V. parahaemolyticus
      specific real-time PCR assay used for this study could estimate elevated V.
      parahaemolyticus levels in oyster mantle fluid within 1 h from sampling time.

PMID- 15553624
TI  - Biochemical and virulence characterization of viable but nonculturable cells of
      Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is a common foodborne pathogen frequently causing
      outbreaks in summer. Maintenance of virulence by the viable but nonculturable
      (VBNC) state of this pathogen would allow its threat to human health to persist.
      This study reports on the change in virulence and concomitant changes in activity
      of two enzymes and fatty acid profiles when V. parahaemolyticus ST550 entered the
      VBNC state in the modified Morita mineral salt-0.5% NaCl medium incubated at 4
      degrees C. The major change in fatty acid composition occurred in the first week,
      with a rapid increase in C15:0 fatty acid and saturated/unsaturated ratio while a
      rapid decrease in C16:1 was observed. The activity level of the inducible
      protective enzyme superoxide dismutase became undetectable in the VBNC state,
      whereas that of constitutive glucose-6-phosphate dehydrogenase did not change in
      either the exponential phase or the VBNC state. Cytotoxicity against HEp-2 cells
      and a suckling mouse assay showed that virulence was lowered in the VBNC state
      compared with exponential-phase cells. Longer incubation times were required by
      the VBNC cells to achieve the same level of virulence as seen in exponential
      phase cells. Culturable cells were recovered on selective agar medium from the
      VBNC cultures injected into suckling mice, probably as the result of in vivo
      resuscitation. Results of this study add to our understanding of the biochemical
      and physiological changes that have not been reported when V. parahaemolyticus
      enters into the VBNC state.

PMID- 15553625
TI  - Effects of recovery, plating, and inoculation methods on quantification of
      Escherichia coli O157:H7 and Listeria monocytogenes from strawberries.
AB  - Effects of different recovery and inoculation methods on quantification of
      Escherichia coli O157:H7 and Listeria monocytogenes from strawberries were
      studied. Strawberries were spot or dip inoculated with 7 to 8 log CFU per
      strawberry of each pathogen, air dried for 2 h, and stored for 1, 3, and 7 days
      at 4 degrees C. The inoculated samples were stomached or washed with phosphate
      buffered saline (PBS; pH 7.2) or with modified PBS (pH 8.4). Bacterial levels
      were determined using a direct selective plating, thin agar layer plating, or
      membrane-transferring plating (MTP) with tryptic soy agar and sorbital MacConkey
      agar (E. coli O157:H7) or modified Oxford agar (L. monocytogenes). Under most
      test conditions, washing with PBS followed by MTP had significantly higher (P <
      0.05) recovery for both bacteria compared with other tested methods. Within a 7
      day storage period for spot-inoculated strawberries, a stomaching step resulted
      in an injury of 0.9 to 1.4 log CFU for E. coli O157: H7 and 1.4 to 1.7 log CFU
      for L. monocytogenes. When a washing step was used instead, this resulted in an
      injury of only 0.2 to 0.6 log CFU for E. coli O157:H7 and 0.2 to 0.7 log CFU for
      L. monocytogenes. Both bacteria could survive on strawberry surfaces, but their
      recovered levels decreased with the increase of storage time at 4 degrees C for
      both spot and dip inoculation methods. Dip inoculation generally had a lower
      recovery than spot inoculation. An ideal protocol to recover and enumerate E.
      coli O157:H7 and L. monocytogenes from strawberries involved shaking and washing
      samples with 100 ml of PBS for 15 min at 22 degrees C coupled with a MTP
      enumeration method.

PMID- 15553626
TI  - Fate of Escherichia coli O157:H7 and Listeria monocytogenes in strawberry juice
      and acidified media at different pH values and temperatures.
AB  - Survival and growth of Escherichia coli O157:H7 and Listeria monocytogenes in
      strawberry juice and acidified media at different pH levels (pH 3.4 to 6.8) and
      temperatures were studied. Sterile strawberry juice (pH 3.6) and acidified
      trypticase soy broth (TSB) media (pH 3.4 to 6.8) were inoculated with
      approximately 6.7 log CFU/ml E. coli O157:H7 or 7.3 log CFU/ ml L. monocytogenes,
      incubated for 3 days at 4 and 37 degrees C. Bacterial levels were determined
      after 2 h, 1 day, and 3 days using surface plating nonselectively on tryptic soy
      agar and selectively on sorbitol MacConkey agar for E. coli O157:H7 or modified
      Oxford agar for L. monocytogenes. A spectrophotometer (660 nm) was also used to
      study growth inhibition of L. monocytogenes in different TSB and strawberry juice
      media (pH 3.4 to 7.3). E. coli O157:H7 survived well at pH values of 3.4 to 6.8
      at 4 degrees C, but the number of injured cells increased as pH decreased and
      incubation time increased. At 37 degrees C, E. coli O157:H7 was inactivated at pH
      of < or = 3.6 but could grow at pH 4.7. L. monocytogenes was quickly injured at
      pH of < or = 4.7 within 2 h of storage at 4 degrees C and then was slightly and
      gradually inactivated as storage time increased. L. monocytogenes survived well
      at pH 6.8 at 4 degrees C and grew well at 37 degrees C. Growth of L.
      monocytogenes at 37 degrees C was inhibited in TSB by 1% citric acid and 0.5%
      malic acids at pH 3.4 or by 50% strawberry juice at pH 4.7. Bacterial injury and
      inactivation appeared to be induced by the acids in strawberry juice. The acids,
      pH value, temperature, and time were important factors for bacterial survival,
      inactivation, and growth in the media tested.

PMID- 15553627
TI  - Decontamination of strawberries using batch and continuous chlorine dioxide gas
      treatments.
AB  - Efficacy of chlorine dioxide (ClO2) gas in reducing Escherichia coli O157:H7 and
      Listeria monocytogenes on strawberries was determined using batch and continuous
      flow ClO2 gas treatment systems. Effects of continuous ClO2 gas treatment on
      total aerobic plate count, color, and residual ClO2 and chlorite on strawberries
      were also evaluated. Strawberries were spot inoculated with 7 to 8 log CFU per
      strawberry of each pathogen (E. coli O157:H7 and L. monocytogenes), stored for 1
      day at 4 degrees C, and treated at 22 degrees C and 90 to 95% relative humidity
      with 0.2 to 4.0 mg/liter ClO2 gas for 15 or 30 min using a batch treatment system
      or with 0.6, 1.8, and 3.0 mg/liter for 10 min using a continuous treatment
      system. Surviving microbial populations were determined using a membrane-transfer
      plating recovery method. Increased ClO2 gas concentrations resulted in increased
      log reductions of each pathogen for both the batch and continuous systems. A
      batch treatment of strawberries with 4 mg/liter ClO2 for 30 min and continuous
      treatment with 3 mg/liter ClO2 for 10 min achieved greater than a 5-log reduction
      for both E. coli O157:H7 and L. monocytogenes. After continuous exposure to 3.0
      mg/liter ClO2 gas for 10 min followed by 1 week of storage at 4 degrees C, no
      aerobic microorganisms were detected and the color of the strawberry surface did
      not change significantly (P > 0.05). Residues of ClO2 and chlorite on
      strawberries after the treatment were 0.19 +/- 0.33 mg ClO2 per kg and 1.17 +/-
      2.02 mg Cl2 per kg, respectively, whereas after 1 week of storage no ClO2
      residues were detected and residual chlorite levels were down to 0.07 +/- 0.12 mg
      Cl2 per kg. These results suggest that ClO2 gas treatment is an effective
      decontamination technique for improving the safety of strawberries while
      extending shelf life.

PMID- 15553628
TI  - Control of Listeria monocytogenes on frankfurters with antimicrobials in the
      formulation and by dipping in organic acid solutions.
AB  - The antilisterial activity of sodium lactate (SL) and sodium diacetate (SD) was
      evaluated in a frankfurter formulation and in combination with a dipping
      treatment into solutions of lactic acid or acetic acid after processing and
      inoculation. Pork frankfurters were formulated with 1.8% SL or 0.25% SD or
      combinations of 1.8% SL with 0.25 or 0.125% SD. After processing, frankfurters
      were inoculated (2 to 3 log CFU/cm2) with a 10-strain composite of Listeria
      monocytogenes and left undipped or were dipped (2 min) in 2.5% solutions of
      lactic acid or acetic acid (23 +/- 2 degrees C) before vacuum packaging and
      storage at 10 degrees C for 40 days. Total microbial populations and L.
      monocytogenes, lactic acid bacteria, and yeasts and molds were enumerated during
      storage. Sensory evaluations also were carried out on frankfurters treated and/or
      formulated with effective antimicrobials. The combination of 1.8% SL with 0.25%
      SD provided complete inhibition of L. monocytogenes growth throughout storage.
      Dipping in lactic acid or acetic acid reduced initial populations by 0.7 to 2.1
      log CFU/cm2, but during storage (12 to 20 days), populations on dipped samples
      without antimicrobials in the formulation reached 5.5 to 7.9 log CFU/cm2. For
      samples containing single antimicrobials and dipped in lactic acid or acetic
      acid, L. monocytogenes growth was completely inhibited or reduced over 12 and 28
      days, respectively, whereas final populations were lower (P < 0.05) than those in
      undipped samples of the same formulations. Bactericidal effects during storage
      (reductions of 0.6 to 1.0 log CFU/ cm2 over 28 to 40 days) were observed in
      frankfurters containing combinations of SL and SD that were dipped in organic
      acid solutions. Inclusion of antimicrobials in the formulation and/or dipping the
      product into organic acid solutions did not affect (P > 0.05) the flavor and
      overall acceptability of products compared with controls. The results of this
      study may be valuable to meat processors as they seek approaches for meeting new
      regulatory requirements in the United States.

PMID- 15553629
TI  - Control of growth and survival of Listeria monocytogenes on smoked salmon by
      combined potassium lactate and sodium diacetate and freezing stress during
      refrigeration and frozen storage.
AB  - In this study, we evaluated the antimicrobial effects of different levels of a
      potassium lactate (PL) plus sodium diacetate (SDA) mixture against the growth and
      survival of Listeria monocytogenes Scott A inoculated onto smoked salmon stored
      at 4, 10, and -20 degrees C. The effect of freezing stress on the growth kinetics
      of L. monocytogenes Scott A on smoked salmon at 4 and 10 degrees C was also
      investigated. The use of PL+SDA at all tested levels (1.5, 3.3, and 5% of a 60%
      commercial solution of PURASAL P Opti. Form 4) completely inhibited the growth of
      L. monocytogenes Scott A on smoked salmon stored at 4 degrees C during 32 days of
      storage. It also delayed the growth of L. monocytogenes Scott A on smoked salmon
      stored at 10 degrees C for up to 11 days, but a listeriostatic effect was
      observed only with 5% PURASAL P Opti. Form 4 at 10 degrees C after 11 days.
      Addition of PL+SDA at all tested levels decreased the surviving populations of L
      monocytogenes Scott A on smoked salmon during 10 months of frozen storage at -20
      degrees C. Freezing stress significantly (P < 0.001) extended the lag time and
      delayed the growth of L. monocytogenes Scott A at both 4 and 10 degrees C.
      However, the effect of freezing stress was more significant at 4 degrees C than
      at 10 degrees C, indicating the importance of temperature control of smoked
      salmon during the retail storage period.

PMID- 15553630
TI  - Effect of prepackage and postpackage pasteurization on postprocess elimination of
      Listeria monocytogenes on deli turkey products.
AB  - Surface pasteurization for inactivation of Listeria monocytogenes was evaluated
      for radiant heat prepackage pasteurization, submersed water postpackage
      pasteurization, and combinations of the two techniques on various types of ready
      to-eat deli turkey products obtained from at least four different manufacturers.
      Products were inoculated either by in-package liquid inoculum or surface sponge
      contact with approximately 10(9) CFU of L. monocytogenes. Additional testing of
      radiant heat pasteurization was performed with low-level inoculation of product
      undersides with approximately 100 CFU of L. monocytogenes followed by enrichment
      recovery after pasteurization. Prepackage pasteurization provided 2.0 to 2.8 log
      reductions when processed for 60 s and 2.8 to 3.8 log reductions when processed
      for 75 s. An improved radiant oven provided 3.53 (60 s) and 4.76 (75 s) log
      reductions of L. monocytogenes. No positive samples were detected after
      enrichment when 40 samples of deli turkey (4 to 4.5 kg) undersides were
      inoculated at low levels and processed for 75 s. Submersed water postpackage
      pasteurization provided 1.95 to 3.0 log reductions when processed for 2, 3, 4, or
      5 min, and combinations of the two processes gave 3.0 to 4.0 log inactivation of
      L. monocytogenes using either 60 + 60 s or 60 + 90 s for the prepackage and
      postpackage pasteurization processes, respectively. These processes, either
      individually or in combination, can provide postprocess elimination of bacteria
      for the manufacture of safe ready-to-eat deli meats.

PMID- 15553631
TI  - Prevalence and typing of Listeria monocytogenes in ready-to-eat food products on
      the Belgian market.
AB  - Listeria monocytogenes is a major concern to producers of ready-to-eat foods
      because of the high mortality rate associated with listeriosis and the widespread
      nature of the organism. To investigate the prevalence of this pathogen in
      different ready-to-eat food products on the Belgian market, a variety of 252
      ready-to-eat food products, mainly fish and meat products, were analyzed.
      Overall, L. monocytogenes was detected in 23.4% of the samples. The highest
      prevalence of L. monocytogenes was found in prepared minced meat (42.1%) and
      smoked halibut (33.3%). Contamination levels were in most cases low (<10 CFU/g);
      however, levels higher than 100 CFU/g were detected in some samples of smoked
      salmon, smoked halibut, and prepared minced meat. A high prevalence of Listeria
      innocua (15.8%) and Listeria welshimeri (36.8%) was detected in prepared minced
      meat. L. monocytogenes strains isolated from different contaminated products were
      subjected to repetitive element sequence-based PCR (REP-PCR) typing to determine
      possible associations with product type, producer, or market. REP-PCR patterns
      were analyzed using BioNumerics software, and seven different groups with at
      least 90% similarity were identified. The cluster analysis indicates that cross
      contamination occurred at the producer and retail level. Serotype identification
      of the strains by PCR revealed that most belonged to the 1/2a(3a) serotype group.

PMID- 15553632
TI  - Strain-specific differences in the attachment of Listeria monocytogenes to
      alfalfa sprouts.
AB  - Contamination of fresh produce with Listeria monocytogenes has resulted in
      outbreaks of systemic listeriosis and febrile gastroenteritis. Recalls of alfalfa
      sprouts have occurred due to contamination with L. monocytogenes. Alfalfa sprouts
      were used as a preharvest model to study the interaction with this human
      pathogen. Seventeen strains were assessed for their capacity to colonize alfalfa
      sprouts, and strain-specific differences (not related to source, serotype, or
      lineage) were revealed when the sprout irrigation water was changed daily. Two of
      the strains colonized and attached to the sprouts very well, reaching levels of
      more than 5 log CFU per sprout. The remaining strains varied in their final
      levels on sprouts between less than 1 to 4.7 log CFU per sprout. All of the L.
      monocytogenes strains grew to equivalent levels on the sprouts when the
      irrigation water was not changed, suggesting the differences observed with
      regular changing of the water resulted from differences in attachment. Further
      analysis of the best colonizing strains indicated that only between 0.3 and 1 log
      CFU per sprout could be removed by additional washing of the sprout, and the
      presence of normal sprout bacteria did not compete with the L. monocytogenes
      strains on the sprouts. The poorest colonizing strain was able to grow in the
      irrigation water during the experiment but could not attach to the sprouts.
      Microscopic examination of the sprouts with L. monocytogenes expressing the green
      fluorescent protein indicated that L. monocytogenes was associated with the root
      hairs of the sprouting alfalfa, with few to no cells visible elsewhere on the
      sprout.

PMID- 15553633
TI  - Dairy farm reservoir of Listeria monocytogenes sporadic and epidemic strains.
AB  - Identifying the reservoirs of a pathogen is vital for control of sporadic disease
      and epidemics. Listeria monocytogenes is a zoonotic foodborne pathogen that is
      responsible for 28% of food-related deaths in the United States annually, as well
      as a major cause of massive product recalls worldwide. To examine the role of the
      dairy farm as a potential source or reservoir for L. monocytogenes subtypes shown
      to cause human listeriosis, we compared the pulsed-field gel electrophoresis
      (PFGE) restriction enzyme digestion profiles of L. monocytogenes dairy farm
      associated strains (milk, environmental, and bovine) to human sporadic and
      epidemic disease strains. Twenty-three percent of human sporadic strains had PFGE
      patterns identical to that of farm isolate(s). Additionally, three farm
      environmental strains and one human sporadic strain had a PFGE pattern identical
      to a strain of L. monocytogenes responsible for the 1985 California epidemic.
      These data indicate that this epidemic strain continues to cause sporadic human
      illness and has a potential dairy farm as a reservoir.

PMID- 15553634
TI  - Longitudinal studies on Listeria in smoked fish plants: impact of intervention
      strategies on contamination patterns.
AB  - Four ready-to-eat smoked fish plants were monitored for 2 years to study Listeria
      contamination patterns and the impact of plant-specific Listeria control
      strategies, including employee training and targeted sanitation procedures, on
      Listeria contamination patterns. Samples from the processing plant environment
      and from raw and finished product were collected monthly and tested for Listeria
      spp. and Listeria monocytogenes. Before implementation of intervention
      strategies, 19.2% of raw product samples (n = 276), 8.7% of finished product
      samples (n = 275), and 26.1% of environmental samples (n = 617) tested positive
      for Listeria spp. During and after implementation of Listeria control strategies,
      19.0% of raw product samples (n = 242), 7.0% of finished product samples (n =
      244), and 19.5% of environmental samples (n = 527) were positive for Listeria
      spp. In one of the four fish plants (plant 4), no environmental samples were
      positive for L. monocytogenes, and this plant was thus excluded from statistical
      analyses. Based on data pooled from plants 1, 2, and 3, environmental Listeria
      spp. prevalence was significantly lower (P < 0.05) for nonfood contact surfaces
      and the finished product area and for the overall core environmental samples
      after implementation of control strategies. Listeria prevalence for floor drains
      was similar before and after implementation of controls (49.6 and 54.2%,
      respectively). Regression analysis revealed a significant positive relationship
      (P < 0.05) between L. monocytogenes prevalence in the environment and in finished
      products before implementation of control strategies; however, this relationship
      was absolved by implementation of Listeria control strategies. Molecular
      subtyping (EcoRI ribotyping) revealed that specific L. monocytogenes ribotypes
      persisted in three processing plants over time. These persistent ribotypes were
      responsible for all six finished product contamination events detected in plant
      1. Ribotype data also indicated that incoming raw material is only rarely a
      direct source of finished product contamination. While these data indicate that
      plant-specific Listeria control strategies can reduce cross-contamination and
      prevalence of Listeria spp. and L. monocytogenes in the plant environment,
      elimination of persistent L. monocytogenes strains remains a considerable
      challenge.

PMID- 15553635
TI  - Direct detection and identification of lactic acid bacteria in a food processing
      plant and in meat products using denaturing gradient gel electrophoresis.
AB  - We established a novel system using denaturing gradient gel electrophoresis
      (DGGE) to quickly identify bacteria known to be responsible for spoilage in meat
      processing plants and meat products. We extracted bacterial DNA from swabbed
      samples at various locations in the plant and from meat products and performed
      PCR amplification, targeting 16S rDNA from the dominant organisms. The
      amplification products were subjected to DGGE, and the contaminating bacteria in
      the meat products and the plant were analyzed. This analysis indicated that
      lactic acid bacteria and spoilage-causing bacteria are widely distributed within
      the meat processing plant. We developed molecular size markers to identify the
      dominant organisms obtained from the plant and meat products. The establishment
      of the present method allows quick and simple identification of bacteria causing
      the possible deterioration of products and contamination and thus permits
      constant monitoring of any harmful bacteria within meat processing plants.

PMID- 15553636
TI  - Sequencing of the tyrosine decarboxylase cluster of Lactococcus lactis IPLA 655
      and the development of a PCR method for detecting tyrosine decarboxylating lactic
      acid bacteria.
AB  - The enzymatic decarboxylation of tyrosine produces tyramine, the most abundant
      biogenic amine in dairy products-especially in cheeses. The screening of lactic
      acid bacteria isolated from different artisanal cheeses and a number of microbial
      collections identified 22 tyramine-producing strains belonging to different
      genera. The Lactococcus lactis strain IPLA 655 was selected, and the genes
      encoding a putative tyrosyl tRNA synthetase, a tyrosine decarboxylase (tdcA), and
      a tyrosine-tyramine antiporter, found together as a cluster, were sequenced. The
      disruption of tdcA yielded a strain unable to produce tyramine. Comparison of the
      L. lactis IPLA 655 tdcA gene with database tdcA sequences led to the design of
      two primers for use in a PCR method that identified potential tyramine-producing
      strains. The proposed method can use purified DNA, isolated colonies, milk, curd,
      and even cheese as a template. Molecular tools for the rapid detection of
      tyramine-producing bacteria at any time during the fermentation process could
      help prevent tyramine accumulation in fermented foods. The proposed technique
      could be of great use to the food industry.

PMID- 15553637
TI  - Comparison of pressure and heat resistance of Clostridium botulinum and other
      endospores in mashed carrots.
AB  - Inactivation of bacterial endospores in food requires a combination of pressure
      and moderate heat. Endospore resistance of seven Clostridium botulinum strains
      was compared with those of Bacillus spp. (B. cereus, B. subtilis, B.
      licheniformis, B. smithii, B. amyloliquefaciens) and Thermoanaerobacterium
      thermosaccharolyticum with respect to pressure (600 to 800 MPa) and temperature
      (80 to 116 degrees C) treatments in mashed carrots. A large variation was
      observed in the pressure resistance of C. botulinum spores. Their reduction after
      treatments with 600 MPa at 80 degrees C for 1 s ranged from more than 5.5 log
      units to no reduction. Spores of the proteolytic C. botulinum TMW 2.357 exhibited
      a greater resistance to pressure than spores from all other bacteria examined,
      with the exception of B. amyloliquefaciens. Heat resistance of spores did not
      correlate with pressure resistance, either within strains of C. botulinum or when
      C. botulinum spores were compared with spores of T. thermosaccharolyticum. A
      quantitative release of dipicolinic acid was observed from C. botulinum spores on
      combined pressure and temperature treatments only after inactivation of more than
      99.999% of the spores. Thus, dipicolinic acid is released by a physicochemical
      rather than a physiological process. The resistance of spores to combined
      pressure and temperature treatments correlated with their ability to retain
      dipicolinic acid. B. amyloliquefaciens, a mesophilic organism that forms highly
      pressure-resistant spores is proposed as a nonpathogenic target organism for high
      pressure process development.

PMID- 15553638
TI  - Radiation-heat synergism for inactivation of Alicyclobacillus acidoterrestris
      spores in citrus juice.
AB  - The objective of this study was to investigate the influence of electron-beam and
      gamma-ray irradiation and temperature (85 to 95 degrees C) on Alicyclobacillus
      acidoterrestris GD3B strain (NCIMB 13137) spores by calculating and comparing the
      decimal reduction dose or time (D-values). The survival rate of A.
      acidoterrestris spores decreased exponentially with irradiation doses of an
      electron beam or gamma ray. D-values determined for electron-beam and gamma-ray
      irradiated spores on filter paper ranged from 1.02 to 1.10 kGy. On the other
      hand, the thermal sterilization effect showed a single exponential decrease
      within 1.5-log decreases in cell numbers (D85 degrees C = 70.5 min, D90 degrees C
      = 16.1 min, and D95 degrees C = 5.19 min and z-value [change in temperature
      required to change the D-value] was 8.83 degrees C), and prolonged heating
      produced an increase of 10 to 13 times that of the thermal resistance. However,
      within all time ranges studied (5 to 360 min), a linear decrease in the D-value
      was observed with an increase in the temperature. A combination of two different
      methods, irradiation before heating, was appropriate for reducing the duration of
      the heat treatment required to achieve the inactivation of conidia. Moreover, a
      necessary radiation dosage for complete inactivation of A. acidoterrestris spores
      that contaminated dextrin was examined. Dextrin is often used in the juice
      industry as an augmentor, and it is known to be sometimes contaminated by these
      spores. The D-values of the spores in dextrin for electron-beam and gamma-ray
      irradiations were 1.72 and 1.79 kGy, respectively. The doses required for
      elimination of the spores could be lowered by using irradiation in combination
      with heat sterilization. When dextrin powder contaminated with 10(4) CFU/g of A.
      acidoterrestris was preirradiated at 1.0 kGy of electron beam, the citrus juice
      containing dextrin at a concentration of 10% (wt/vol) was completely sterilized
      by heating for 20 min at 95 degrees C.

PMID- 15553639
TI  - Efficacy of acidic electrolyzed water ice for pathogen control on lettuce.
AB  - Acidic electrolyzed water (AcEW) was used as frozen AcEW (AcEW-ice) for
      inactivation of Listeria monocytogenes and Escherichia coli O157:H7 on lettuce.
      AcEW-ice was prepared from AcEW with 20, 50, 100, and 200 ppm of available
      chlorine by freezing at -40 degrees C and generated 30, 70, 150, and 240 ppm of
      chlorine gas (Cl2), respectively. The AcEW-ice was placed into styrene-foam
      containers with lettuce samples at 20 degrees C for 24 h. Although AcEW-ice
      generating 30 ppm Cl2 had no effect on L. monocytogenes cell counts, AcEW-ice
      generating 70 to 240 ppm of Cl2 significantly (P < 0.05) reduced L. monocytogenes
      by ca. 1.5 log CFU/g. E. coli O157:H7 cell counts were reduced by 1.0 log CFU/g
      with AcEW-ice generating 30 ppm of Cl2. AcEW-ice generating 70 and 150 ppm of Cl2
      reduced E. coli O157:H7 by 2.0 log CFU/g. Further significant reduction of E.
      coli O157:H7 (2.5 log CFU/g) was demonstrated by treatment with AcEW-ice
      generating 240 ppm of Cl2. However, treatment with AcEW-ice generating 240 ppm of
      Cl2 resulted in a physiological disorder resembling leaf burn. AcEW-ice that
      generated less than 150 ppm of Cl2 had no effect on the surface color of the
      lettuce. AcEW-ice, regardless of the concentration of the emission of Cl2, had no
      effect on the ascorbic acid content in the lettuce. The weight ratio of lettuce
      to AcEW-ice required was determined to be over 1:10. The bactericidal effect of
      AcEW-ice appeared within the first 2 h. The use of AcEW-ice provides
      simultaneously for low temperature storage and inactivation of bacteria.

PMID- 15553640
TI  - Spectroscopic quantification of bacteria using artificial neural networks.
AB  - Fourier transform-infrared spectroscopy, in conjunction with artificial neural
      networks, has been used for identification and classification of selected
      foodborne pathogens. Five bacterial species (Enterococcus faecium, Salmonella
      Enteritidis, Bacillus cereus, Yersinia enterocolitica, Shigella boydii) and five
      Escherichia coli strains (O103, O55, O121, O30, O26) suspended in phosphate
      buffered saline were enumerated to provide seven different concentrations ranging
      from 10(9) to 10(3) CFU/ ml. The trained artificial neural networks were then
      validated with an independent subset of samples and compared with the traditional
      plate count method. It was found that the concentration-based classification of
      the species was 100% correct and the strain-based classification was 90 to 100%
      accurate.

PMID- 15553641
TI  - Detection and identification of bacteria in a juice matrix with Fourier transform
      near infrared spectroscopy and multivariiate analysis.
AB  - The use of Fourier transform-near infrared (FT-NIR) spectroscopy combined with
      multivariate pattern recognition techniques was evaluated to address the need for
      a fast and senisitive method for the detection of bacterial contamination in
      liquids. The complex cellular composition of bacteria produces FT-NIR vibrational
      transitions (overtone and combination bands), forming the basis for
      identification and subtyping. A database including strains of Escherichia coli,
      Pseudomonas aeruginosa, Bacillus subtilis, Bacillus cereus, and Bacillus
      thuringiensis was built, with special care taken to optimize sample preparation.
      The bacterial cells were treated with 70% (vol/vol) ethanolto enhance safe
      handling of pathogenic strains and then concentrated on an aluminum oxide
      membrane to obtain a thin bacterial film. This simple membrane filtration
      procedure generated reproducible FT-NIR spectra that allowed for the rapid
      discrimination among closely related strains. Principal component analysis and
      soft independent modeling of class analogy of transformed spectra in the region
      5,100 to 4,400 cm(-1) were able to discriminate between bacterial species.
      Spectroscopic analysis of apple juices inoculated with different strains of E.
      coli at approximately 10(5) CFU/ml showed that FT-NIR spectralfeatures are
      consistent with bacterial contamination and soft independent modeling of class
      analogy correctly predicted the identity of the contaminant as strains of E.
      coli. FT-NIR in conjunction with multivariate techniques can be used for the
      rapid and accurate evaluation of potential bacterial contamination in liquids
      with minimal sample manipulation, and hence limited exposure of the laboratory
      worker to the agents.

PMID- 15553642
TI  - Determination of thermal inactivation kinetics of microorganisms with a
      continuous microflow apparatus.
AB  - Use of a continuous microflow submerged microcoil (CSMC) apparatus was compared
      with the capillary tube (CT) method for measuring the thermal inactivation
      kinetics of Pseudomonas fluorescens at 61 degrees C for 3 to 29 s. Inocula were
      continuously pumped through a microbore (< or = 0.0762 cm inside diameter) thin
      walled stainless steel capillary tube submerged in a heated oil bath. The heating
      time was set by changing the flow rate, tube dimensions, or both. With the use of
      microthermo-couples, the time for the inocula to reach within 1 degree C of the
      set temperature was <3 s, and shorter than that with capillary tubes or vials.
      Inactivation curves (61 degrees C) for P. fluorescens prepared by the CSMC method
      were not different from curves prepared by the CT method, as determined by
      analysis of variance (P > 0.05). Inactivation of Bacillus cereus spores (105
      degrees C) and native microflora found in raw milk (72 degrees C) over heating
      times of 3 to 42 s were determined by CSMC. CSMC can measure thermal inactivation
      kinetics of microorganisms efficiently and simply at high temperatures and in
      short times. Survivors can be enumerated in 1-ml volumes of heat-treated samples,
      making it useful for determining inactivation kinetics of low numbers of
      microorganisms, such as those found in high-quality raw milk. Inactivation
      kinetics were generally more accurately described by the Weibull function (R2 >
      or = 0.97) than the linear kinetic model.

PMID- 15553643
TI  - High-performance liquid chromatography multiresidue method for the determination
      of N-methyl carbamates in fruit and vegetable juices.
AB  - A rapid multiresidue method has been developed for the analysis of N
      methylcarbamate insecticides (oxamyl, methomyl, propoxur, carbofuran, carbaryl,
      and methiocarb) in fruit and vegetable juices. The method is based on the
      adsorption of the N-methyl carbamates in Florisil and the subsequent extraction
      of pesticides using a low volume of acetone. Residue levels in juice were
      determined by reversed-phase high-performance liquid chromatography with
      fluorescence detection after postcolumn derivatization. The separation of
      carbamates is performed on a C8 column with water-methanol as mobile phase.
      Recovery studies were performed at 500-, 100-, and 10-ng/ml fortification levels,
      and average recoveries obtained for carbamates ranged from 79 to 109%, with
      relative standard deviations between 1.4 and 9.9%. The method was found to be
      linear over the range assayed from 10 to 1,000 ng/ml, and the detection limits
      for carbamates varied from 0.8 to 1.9 ng/ml.

PMID- 15553644
TI  - Home storage temperatures and consumer handling of refrigerated foods in Sweden.
AB  - The lack of data on consumer refrigeration temperatures and storage times limits
      our ability to assess and manage risks associated with microbial hazards. This
      study addressed these limitations by collecting data on temperatures and storage
      handling practices of chilled foods. Consumers from 102 households in Uppsala,
      Sweden, were instructed to purchase seven food items (minced meat, fresh herring
      fillets, soft cheese, milk, sliced cooked ham, vacuum-packed smoked salmon, and
      ready-to-eat salad) and to store them using their normal practices. They were
      interviewed the next day, and food temperatures were measured. In general, there
      were no significant relations between temperature and characteristics of the
      respondents (e.g., sex, age, education, age of the refrigerator). Mean storage
      temperatures ranged from 6.2 degrees C for minced meat to 7.4 degrees C for ready
      to-eat salad. Maximum temperatures ranged from 11.3 to 18.2 degrees C. Data were
      not significantly different from a normal distribution, except for ready-to-eat
      salad, although distributions other than the normal fitted data better in most
      cases. Five percent to 20% of the food items were stored at temperatures above 10
      degrees C. Most respondents knew the recommended maximum temperature, but less
      than one fourth claimed to know the temperature in their own refrigerator.
      Practical considerations usually determined where food was stored. For products
      with a long shelf life, stated storage times were different for opened and
      unopened packages. The current situation might be improved if consumers could be
      persuaded to use a thermometer to keep track of refrigerator temperature.

PMID- 15553645
TI  - Observation versus self-report: validation of a consumer food behavior
      questionnaire.
AB  - A reliable and validated set of food safety behavior questions that could be used
      with confidence when evaluating food safety education programs was identified in
      this study. A list of 29 food-handling and consumption behaviors rank-ordered
      within five pathogen control factors by nationally recognized food safety experts
      was the basis for the development of the behavior questions. Questions were
      evaluated for reliability and several forms of validity. During a kitchen
      activity session, 70 graduates of a nutrition education program completed four
      food preparation tasks while being observed and videotaped. The individuals also
      participated in an in-depth interview to validate behaviors that could not be
      observed during the food preparation activity, e.g., refraining from preparing
      food for others when experiencing diarrhea. Criterion validity was established by
      comparing questionnaire responses to observed behavior and interview responses.
      Twenty-eight questions met the validity criterion (> or = 70% agreement between
      observed and interviewed responses and self-reported responses), with three or
      more questions from each of five pathogen control factor areas. Observation
      assessments revealed that hand washing was more likely to be performed prior to
      beginning food preparation than between working with raw meats and fresh produce.
      Errors in methods of washing hands, utensils, and preparation surfaces between
      food preparation tasks were common. Most participants did not use thermometers to
      evaluate doneness but still cooked to safe internal temperatures. The results
      provide a tool that educators can use to evaluate food safety programs and will
      help guide the development of more effective food safety education programs
      targeting needed improvements in behavioral skills.

PMID- 15553646
TI  - An application of meta-analysis in food safety consumer research to evaluate
      consumer behaviors and practices.
AB  - Meta-analysis provides a structured method for combining results from several
      studies and accounting for and differentiating between study variables. Numerous
      food safety consumer research studies often focus on specific behaviors among
      different subpopulations but fail to provide a holistic picture of consumer
      behavior. Combining information from several studies provides a broader
      understanding of differences and trends among demographic subpopulations, and
      thus, helps in developing effective risk communication messages. In the
      illustrated example, raw/undercooked ground beef consumption and hygienic
      practices were evaluated according to gender, ethnicity, and age. Percentages of
      people engaging in each of the above behaviors (referred to as effect sizes) were
      combined using weighted averages of these percentages. Several measures,
      including sampling errors, random variance between studies, sample sizes of
      studies, and homogeneity of findings across studies, were used in the meta
      analysis. The statistical significance of differences in behaviors across
      demographic segments was evaluated using analysis of variance. The meta-analysis
      identified considerable variability in effect sizes for raw/undercooked ground
      beef consumption and poor hygienic practices. More males, African Americans, and
      adults between 30 and 54 years (mid-age) consumed raw/undercooked ground beef
      than other demographic segments. Males, Caucasians, and Hispanics and young
      adults between 18 and 29 years were more likely to engage in poor hygienic
      practices. Compared to traditional qualitative review methods, meta-analysis
      quantitatively accounts for interstudy differences, allows greater consideration
      of data from studies with smaller sample sizes, and offers ease of analysis as
      newer data become available, and thus, merits consideration for its application
      in food safety consumer research.

PMID- 15553647
TI  - Inactivation of Saccharomyces cerevisiae suspended in orange juice using high
      intensity pulsed electric fields.
AB  - Saccharomyces cerevisiae is often associated with the spoilage of fruit juices.
      The purpose of this study was to evaluate the effect of high-intensity pulsed
      electric field (HIPEF) treatment on the survival of S. cerevisiae suspended in
      orange juice. Commercial heat-sterilized orange juice was inoculated with S.
      cerevisiae (CECT 1319) (10(8) CFU/ml) and then treated by HIPEFs. The effects of
      HIPEF parameters (electric field strength, treatment time, pulse polarity,
      frequency, and pulse width) were evaluated and compared to those of heat
      pasteurization (90 degrees C/min). In all of the HIPEF experiments, the
      temperature was kept below 39 degrees C. S. cerevisiae cell damage induced by
      HIPEF treatment was observed by electron microscopy. HIPEF treatment was
      effective for the inactivation of S. cerevisiae in orange juice at pasteurization
      levels. A maximum inactivation of a 5.1-log (CFU per milliliter) reduction was
      achieved after exposure of S. cerevisiae to HIPEFs for 1,000 micros (4-micros
      pulse width) at 35 kV/cm and 200 Hz in bipolar mode. Inactivation increased as
      both the field strength and treatment time increased. For the same electric field
      strength and treatment time, inactivation decreased when the frequency and pulse
      width were increased. Electric pulses applied in the bipolar mode were more
      effective than those in the monopolar mode for destroying S. cerevisiae. HIPEF
      processing inactivated S. cerevisiae in orange juice, and the extent of
      inactivation was similar to that obtained during thermal pasteurization. HIPEF
      treatments caused membrane damage and had a profound effect on the intracellular
      organization of S. cerevisiae.

PMID- 15553648
TI  - Colicin concentrations inhibit growth of Escherichia coli O157:H7 in vitro.
AB  - Escherichia coli O157:H7 is a virulent foodborne pathogen that causes severe
      human illness and inhabits the intestinal tract of food animals. Colicins are
      antimicrobial proteins produced by E. coli strains that inhibit or kill other E.
      coli. In the present Study, the efficacy of three pore-forming colicins (El, N,
      and A) were quantified in vitro against E. coli O157:H7 strains 86-24 and 933.
      Colicins E1 and N reduced the growth of E. coli O157:H7 strains, but the efficacy
      of each colicin varied among strains. Colicin E1 was more effective against both
      strains of E. coli O157:H7 than colicins A and N and reduced (P < 0.05)
      populations of E. coli O157:H7 at concentrations <0.1 microg/ml. These potent
      antimicrobial proteins may potentially provide an effective and environmentally
      sound preharvest strategy to reduce E. coli O157:H7 in food animals.

PMID- 15553649
TI  - Antibacterial effect of water-soluble tea extracts on foodborne pathogens in
      laboratory medium and in a food model.
AB  - The microbial inhibition of foodborne pathogens was determined in brain heart
      infusion broth with 10% (wt/vol) water-soluble extracts of green, jasmine, black,
      dungglre, and oolong tea against Escherichia coli O157:H7, Salmonella enterica
      serovar Enteritidis, Listeria monocytogenes, and Staphylococcus aureus. The mixed
      culture (approximately 6.0 log CFU/ml), which was composed of the four pathogens,
      was inoculated into brain heart infusion broth with and without tea extracts.
      After incubation at 35 degrees C for 0, 1, 3, and 5 days, proper dilution of each
      sample was spiral plated on each selective agar. Viable cell counts were
      performed after incubation at 35 degrees C for 24 to 36 h. Green, jasmine, and
      black tea exhibited an approximately 5.0 log suppression of S. aureus compared
      with the control from days 1 to 5. Green and jasmine tea also suppressed the
      growth of L. monocytogenes by approximately 3.0 log CFU/ml on day 5. In contrast,
      no tea extracts inactivated E. coli O157:H7 and Salmonella Enteritidis. Based on
      the result in liquid medium, green and jasmine teas of 0.1% (vol/wt) were
      individually evaluated for their antimicrobial activity against L. monocytogenes
      and S. aureus in a food model (ground beef) stored at 7 degrees C for 0, 1, 3, 5,
      and 7 days. Viable cell counts of total bacteria, L. monocytogenes, and S. aureus
      in ground beef were not significantly different among green and jasmine tea and
      the control.

PMID- 15553650
TI  - Identification of Enterobacteriaceae from washed and unwashed commercial shell
      eggs.
AB  - To evaluate the effect of processing on the safety and quality of retail shell
      eggs, a storage study was conducted with unwashed and commercially washed eggs.
      This work demonstrated that commercial processing decreased microbial
      contamination of eggshells. To know which species persisted during storage on
      washed or unwashed eggs, Enterobacteriaceae isolates were selected and identified
      biochemically. For each of three replications, shell eggs were purchased from a
      commercial processing plant, transported back to the laboratory, and stored at 4
      degrees C. Once a week for 6 weeks, 12 eggs for each treatment (washed and
      unwashed control) were rinsed in sterile phosphate-buffered saline. A 1-ml
      aliquot of each sample was plated onto violet red bile glucose agar with overlay
      and incubated at 37 degrees C for 24 h. Following incubation, plates were
      observed for colonies characteristic of the family Enterobacteriaceae. A maximum
      of 10 isolates per positive sample were streaked for isolation before being
      identified to the genus or species level using commercially available biochemical
      strips. Although most of the isolates from the unwashed control eggs belonged to
      the genera Escherichia or Enterobacter, many other genera and species were
      identified. These included Citrobacter, Klebsiella, Kluyvera, Pantoea,
      Providencia, Rahnella, Salmonella, Serratia, and Yersinia. Non-Enterobacteriaceae
      also recovered from the unwashed egg samples included Xanthomonas and Flavimonas.
      Very few washed egg samples were contaminated with any of these bacteria. These
      data provide useful information on the effectiveness of processing in removing
      microorganisms from commercial shell eggs.

PMID- 15553651
TI  - Demonstration of the applicability of the Weibull-log-logistic survival model to
      the isothermal and nonisothermal inactivation of Escherichia coli K-12 MG1655.
AB  - Published isothermal semilogarithmic survival curves of Escherichia coli K-12
      MG1655, in the range of 49.8 to 60.6 degrees C, all had noticeable downward
      concavity. They could be described by the model log S(t) = -b(T)t n, where S(t) =
      N(t)/N0, N(t) and N0 being the momentary and initial number of organisms,
      respectively; b(T) is a temperature-dependent rate parameter; and n is a constant
      found to be about 1.5. The temperature dependence of b(T) could be described by
      the log-logistic model, b(T) = ln[1 + exp[k(T - Tc)]], which had an almost
      perfect fit, with k = 0.88 degrees C(-1) and Tc = 60.5 degrees C. The constants,
      n, k, and Tc were considered the organism's survival parameters in the particular
      medium. They were incorporated into a rate equation on the assumption that in
      nonisothermal heating, the momentary inactivation rate is the isothermal rate at
      the momentary temperature at a time that corresponds to the momentary survival
      ratio. This model's estimates matched the actual survival curves obtained in the
      same work under two different nonisothermal heating profiles, lending support to
      the notion that the Weibull-log-logistic model combination can be used not only
      to describe isothermal inactivation mathematically, but also to predict survival
      patterns under nonisothermal conditions.

PMID- 15553653
TI  - Sound-based relief.

PMID- 15553652
TI  - Detection of aflatoxin-producing molds in Korean fermented foods and grains by
      multiplex PCR.
AB  - An assay based on multiplex PCR was applied for the detection of potential
      aflatoxin-producing molds in Korean fermented foods and grains. Three genes,
      avfA, omtA, and ver-1, coding for key enzymes in aflatoxin biosynthesis, were
      used as aflatoxin-detecting target genes in multiplex PCR. DNA extracted from
      Aspergillus flavus, Aspergillus parasiticus, Aspergillus oryzae, Aspergillus
      niger, Aspergillus terreus, Penicillium expansum, and Fusarium verticillioides
      was used as PCR template to test specificity of the multiplex PCR assay. Positive
      results were achieved only with DNA that was extracted from the aflatoxigenic
      molds A. flavus and A. parasiticus in all three primer pairs. This result was
      supported by aflatoxin detection with direct competitive enzyme-linked
      immunosorbent assay (DC-ELISA). The PCR assay required just a few hours, enabling
      rapid and simultaneous detection of many samples at a low cost. A total of 22
      Meju samples, 24 Doenjang samples, and 10 barley samples commercially obtained in
      Korea were analyzed. The DC-ELISA assay for aflatoxin detection gave negative
      results for all samples, whereas the PCR-based method gave positive results for 1
      of 22 Meju samples and 2 of 10 barley samples. After incubation of the positive
      samples with malt extract agar, DC-ELISA also gave positive results for aflatoxin
      detection. All Doenjang samples were negative by multiplex PCR and DC-ELISA
      assay, suggesting that aflatoxin contamination and the presence of aflatoxin
      producing molds in Doenjang are probably low.

PMID- 15553654
TI  - Avoiding electromagnetic artifacts when recording auditory steady-state
      responses.
AB  - Electromagnetic artifacts can occur when recording multiple auditory steady-state
      responses evoked by sinusoidally amplitude modulated (SAM) stimuli. High
      intensity air-conducted stimuli evoked responses even when hearing was prevented
      by masking. Additionally, high-intensity bone-conducted stimuli evoked responses
      that were completely different from those evoked by air-conducted stimuli of
      similar sensory level. These artifacts were caused by aliasing since they did not
      occur when recordings used high analog-digital (AD) conversion rates or when high
      frequencies in the electroencephalographic (EEG) signal were attenuated by steep
      slope low-pass filtering. Two possible techniques can displace aliased energy
      away from the response frequencies: (1) using an AD rate that is not an integer
      submultiple of the carrier frequencies and (2) using stimuli with frequency
      spectra that do not alias back to the response frequencies, such as beats or
      "alternating SAM" tones. Alternating SAM tones evoke responses similar to
      conventional SAM tones, whereas beats produce significantly smaller responses.

PMID- 15553655
TI  - ABR and DPOAE indices of normal loudness in children and adults.
AB  - Loudness growth prediction using normal templates of loudness derived with ABR
      and DPOAE measures was investigated in 20 children 4 to 12 years and 20 adults
      with normal hearing. An ABR click latency-intensity function (LIF), ABR 2 kHz
      tone LIF, and DPOAE 2 kHz amplitude-intensity function (AIF) were recorded from
      each listener. A loudness-intensity function was also measured for each
      electrophysiologic stimulus. Children and adults exhibited similar intensity
      functions of ABR latency, DPOAE amplitude, and loudness. A statistically
      significant relationship was found between loudness and ABR latency and DPOAE
      amplitude. Loudness estimation equations derived with ABR latency and DPOAE
      amplitude accurately and reliably predicted the loudness-intensity functions of
      the listeners. Normative ABR and DPOAE templates of predicted loudness growth may
      have clinical application in site-of-lesion assessment or hearing aid fitting by
      distinguishing abnormal rates of loudness growth for individuals who cannot
      provide reliable behavioral measures.

PMID- 15553656
TI  - The effects of body position on distortion-product otoacoustic emission testing.
AB  - Otoacoustic emissions are frequently acquired from patients in a variety of body
      positions aside from the standard, seated orientation. Yet little knowledge is
      available regarding whether these deviations will produce nonpathological changes
      to the clinical results obtained. The present study aimed to describe the effects
      of body position on the distortion-product otoacoustic emissions of 60 normal
      hearing adults. With particular attention given to common clinical practice, the
      Otodynamics ILO292, and the measurement parameters of amplitude, signal-to-noise
      ratio, and noise were utilized. Significant position-related effects and
      interactions were revealed for all parameters. Specifically, stronger emissions
      in the mid frequencies and higher noise levels at the extreme low and high
      frequencies were produced by testing subjects while lying on their side compared
      with the seated position. Further analysis of body position effects on emissions
      is warranted, in order to determine the need for clinical application of position
      dependent normative data.

PMID- 15553657
TI  - Optimizing frequency-to-electrode allocation in cochlear implants.
AB  - This study tested the hypothesis that speech perception of cochlear implant users
      could be improved by increasing the number of electrodes allocated to frequencies
      below 2.6 kHz, with correspondingly fewer electrodes allocated above this point.
      Eight users of the Nucleus CI22 implant participated and wore experimental maps
      in which the widths of the analysis filters were altered to provide either two or
      three extra low-frequency channels. Speech perception was tested following
      periods of take-home experience. Information transmission analysis of vowel and
      consonant confusions appear to support our hypothesis, showing that vowel first
      formant information was significantly better perceived with the experimental map
      and that consonant information was not significantly different. The results of
      CNC word testing appear to contradict this result, showing that the experimental
      map degraded both vowel and consonant perception. Overall, the experimental map
      had a small and variable effect on speech perception. These results do not
      support our hypothesis and indicate that further research is needed to
      investigate the possible effects of narrowing the filter bandwidth in low
      frequencies, as done in this experiment.

PMID- 15553658
TI  - Comparison of custom sounds for achieving tinnitus relief.
AB  - Tinnitus masking has been a widely used method for treating clinically
      significant tinnitus. The method, referred to herein as "sound-based relief,"
      typically uses wearable ear-level devices ("maskers") to effect palliative
      tinnitus relief. Although often effective, this approach is limited to the use of
      broadband noise with the maskers. We hypothesized that the effectiveness of
      treatment can be improved by expanding the auditory-stimulus options available to
      patients. A pilot study was conducted to determine for each of 21 subjects the
      most effective of custom sounds that are designed to promote tinnitus relief.
      While sitting in a sound booth, subjects listened to white noise and to custom
      sounds that are available commercially for providing tinnitus relief. Three sound
      formats ("E-Water," "E-Nature," and "E-Air") were provided by the Dynamic
      Tinnitus Mitigation (DTM-6a) system (Petroff Audio Technologies, Inc.).
      Additionally, seven sounds were provided by the Moses/Lang CD7 system (Oregon
      Hearing Research Center). Considering group data, all of the sounds provided a
      significant reduction in tinnitus annoyance relative to the annoyance of tinnitus
      alone. Two of the commercial sounds (DTM E-Nature and E-Water) were judged
      significantly more effective than the other sounds.

PMID- 15553659
TI  - Levocloperastine in the treatment of chronic nonproductive cough: comparative
      efficacy versus standard antitussive agents.
AB  - The medical and social impact of cough is substantial. Current antitussive agents
      at effective doses have adverse events such as drowsiness, nausea and
      constipation that limit their use. There is also recent evidence that standard
      antitussive agents, such as codeine, may not reduce cough during upper
      respiratory infections. Therefore, there is a need for more effective and better
      tolerated agents. The efficacy of levocloperastine, a novel antitussive, which
      acts both centrally on the cough center and on peripheral receptors in the
      tracheobronchial tree in treating chronic cough, was compared with that of other
      standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in
      six open clinical trials. The studies enrolled patients of all ages with cough
      associated with various respiratory disorders including bronchitis, asthma,
      pneumonia and chronic obstructive pulmonary disease. Levocloperastine
      significantly improved cough symptoms (intensity and frequency of cough) in all
      trials, and improvements were observed after the first day of treatment. In
      children, levocloperastine reduced nighttime awakenings and irritability, and in
      adults it was effective in treating cough induced by angiotensin-converting
      enzyme inhibitors. When compared with other antitussive agents, levocloperastine
      had improved or comparable efficacy, with a more rapid onset of action.
      Importantly, no evidence of central adverse events was recorded with
      levocloperastine, whereas drowsiness was reported by a significant number of
      patients receiving codeine. Levocloperastine is an effective antitussive agent
      for the treatment of cough in patients of all ages. It has a more rapid onset of
      action than standard agents with an improved tolerability profile.

PMID- 15553660
TI  - The effect of long-term treatment with erdosteine on chronic obstructive
      pulmonary disease: the EQUALIFE Study.
AB  - Erdosteine is a new thiol compound with effects on bacterial adhesiveness as well
      as antioxidant and mucoactive properties. The EQUALIFE study, a fully randomized,
      double-blind, placebo-controlled, parallel-group, multicenter study, was designed
      to assets the effectiveness of long-term treatment with erdosteine in patients
      with moderate chronic obstructive pulmonary disease (COPD). One hundred and fifty
      five patients received oral erdosteine, 300 mg b.i.d., or placebo for 8 months
      during the winter season to assess the effect of treatments on exacerbation rate,
      hospitalization, lung function and quality of life, assessed using the Short Form
      36 and the St. George's Respiratory Questionnaire. A pharmacoeconomic analysis
      was also conducted to compare the two treatments. One hundred and twenty-four
      patients completed the study with erdosteine (n = 63) or placebo (n = 61). The
      group of COPD patients who received 8 months of continuous treatment with
      erdosteine had significantly fewer exacerbations and spent fewer days in the
      hospital than did the placebo group; furthermore, they had no loss of lung
      function. Patients in the erdosteine group also showed a significant improvement
      in health-related quality of life. The mean total COPD-related disease costs per
      patient were lower in the erdosteine group than in the placebo group over the
      study period. The results indicate that 8 months of treatment with erdosteine is
      effective in reducing exacerbation and hospitalization rates and in improving
      health status. The study suggests that erdosteine is likely to provide an
      important contribution to the therapy of patients with symptomatic COPD.

PMID- 15553661
TI  - Switch from ABCD pretreatment to A-II-A treatment: a multinational, open,
      centrally randomized, prospective parallel group comparison.
AB  - The aim of this trial was to evaluate the efficacy and safety of switching
      antihypertensive monotherapy from a non-angiotensin II receptor blocker
      treatment, i.e., angiotensin-converting enzyme (ACE) inhibitor, beta-blocker,
      calcium (Ca2+) channel blocker or diuretic, to monotherapy with candesartan
      cilexetil 8 or 16 mg once daily. Patients (age 18-74 years) with mild to moderate
      essential hypertension were enrolled in this multinational, open-label, centrally
      randomized, prospective parallel group study. Previous antihypertensive
      treatment, with either an ACE inhibitor, a beta-blocker, a Ca2+ channel blocker
      or a diuretic, was maintained for a run-in period of 4 weeks and was then
      substituted at the baseline visit where patients were randomized into two groups
      to receive either candesartan cilexetil 8 mg (n = 985) or 16 mg (n = 982) once
      daily for an 8-week treatment period. Blood pressure (BP) reduction was the
      primary endpoint after 4 weeks of therapy and the secondary endpoint after 8
      weeks of therapy. Results of the first 4 weeks of therapy are presented here. A
      total of 1,967 patients were included: 985 received candesartan cilexetil 8 mg
      and 982 candesartan cilexetil 16 mg once daily; 1,879 patients were included in
      the intention-to-treat analysis. The percentages of patients receiving an ACE
      inhibitor, a beta-blocker, a Ca2+ channel blocker or a diuretic as previous
      antihypertensive treatment were 44.7, 18.8, 30.6 and 5.9%, respectively. After 4
      weeks of treatment with candesartan cilexetil 8 and 16 mg, sitting diastolic and
      systolic BP were reduced (mean +/- SD): -7 +/- 10 and -14 +/- 17 mmHg, and -8 +/-
      10 and -16 +/- 16 mmHg, respectively. The percentage of patients who were still
      borderline hypertensive or hypertensive after 4 weeks of substitute treatment was
      lower in the candesartan cilexetil 16 mg group than in the 8 mg group: 7.1 and
      5.3%, respectively, versus 9 and 7.4%, respectively. Reported adverse events were
      mild or moderate in intensity and in accordance with those reported in the
      literature. Candesartan cilexetil can be considered an effective and safe
      alternative to other common antihypertensive monotherapies in a large spectrum of
      patients with mild and moderate hypertension.

PMID- 15553662
TI  - Nifedipine inhibits tumor necrosis factor-alpha-induced leukocyte adhesion to
      endothelial cells by suppressing vascular cell adhesion molecule-1 (VCAM-1)
      expression.
AB  - We have previously shown that nifedipine, one of the most popular dihydropyridine
      based calcium antagonists (DHPs), blocked tumor necrosis factor-alpha (TNF-alpha)
      induced reactive oxygen species generation and subsequent monocyte
      chemoattractant protein-1 expression in endothelial cells (ECs), thus suggesting
      that nifedipine may inhibit monocyte recruitment, an initiating step in
      atherosclerosis. However, the effect of nifedipine on leukocyte adhesion to ECs,
      another pivotal step in the early stage of atherosclerosis, remains to be
      elucidated. In this study, we investigated whether nifedipine could inhibit TNF
      alpha-induced vascular cell adhesion molecule-1 (VCAM-1) expression and
      subsequent leukocyte adhesion to human umbilical vein endothelial cells (HUVEC).
      Nifedipine significantly inhibited TNF-alpha-induced up-regulation of VCAM-1 mRNA
      levels in HUVEC. Furthermore, nifedipine was found to block MOLT-3 (a human
      lymphoblastic cell line) cell adhesion to TNF-alpha-exposed HUVEC. The results
      suggest that nifedipine could inhibit TNF-alpha-induced leukocyte adhesion to ECs
      by suppressing VCAM-1 expression. Our present study provides a novel beneficial
      aspect of nifedipine on atherogenesis.

PMID- 15553663
TI  - Nifedipine inhibits gene expression of receptor for advanced glycation end
      products (RAGE) in endothelial cells by suppressing reactive oxygen species
      generation.
AB  - Advanced glycation end products (AGEs), the senescent macroprotein derivatives
      that form in increased amounts in diabetes, have been implicated in the
      pathogenesis of diabetic vascular complications. Indeed, AGEs elicit oxidative
      stress generation in vascular wall cells through an interaction with their
      receptor (RAGE), thus playing an important role in vascular inflammation and
      altered gene expression of growth factors and cytokines. We have previously shown
      that nifedipine, one of the most popular dihydropyridine-based calcium
      antagonists, blocked tumor necrosis factor-alpha-induced monocyte chemoattractant
      protein-1 expression in endothelial cells (ECs) through its antioxidative
      properties. However, the effects of nifedipine on AGE-exposed ECs remain to be
      elucidated. In this study we investigated whether nifedipine could inhibit the
      AGE-induced reactive oxygen species (ROS) generation and subsequent RAGE gene
      expression in human umbilical vein endothelial cells (HUVEC). Nifedipine
      completely inhibited AGE-induced ROS generation in HUVEC. Furthermore, nifedipine
      was found to prevent up-regulation of RAGE mRNA levels in AGE-exposed HUVEC.
      These results demonstrate that nifedipine can inhibit RAGE overexpression in AGE
      exposed ECs by suppressing ROS generation. Our present study suggests that
      nifedipine may have therapeutic potential in the treatment of patients with AGE
      related disorders such as diabetic vascular complications.

PMID- 15553664
TI  - Effects of uvalino, a new autochthonous wine, on the inhibition of the production
      of hydroxyl radicals.
AB  - In view of the high concentration of resveratrol found in a new autochthonous
      wine (Uvalino) and the notable antioxidant activity of this substance, we decided
      to assess whether this wine could inhibit the production of free radicals.
      Nowadays, free radicals are considered to be the most noxious factors for
      tissues, triggering the development of many diseases. The assessments were
      carried out using a direct and more precise technique, electronic paramagnetic
      resonance (EPR), which is able to detect the ability of an antioxidant agent to
      inhibit the formation of hydroxyl radicals (*OH), which are among the most
      noxious reactive oxygen species (ROS). The results show that Uvalino wine is able
      to eliminate ROS production almost completely. Consequently, it has beneficial
      effects on health in all the diseases in which ROS plays an important
      pathogenetic role.

PMID- 15553665
TI  - [Anti-tumor effect of intratumoral administration of dendritic cells in
      combination with TS-1 and OK-432].
AB  - We investigated the in vivo anti-tumor effect of intratumoral administration of
      dendritic cells (DCs) after chemotherapy using TS-1, and followed by
      immunopotentiator OK-432. Both in Meth-A-bearing BALB/c and in SCCV II-bearing
      C3H/HeN mice, one week of oral administration of TS-1 affected a partial
      eradication of established tumors. TS-1 followed by DCs and OK-432 resulted in a
      marked inhibition in tumor growth, and also contributed to a greater prolongation
      of survival. Cytotoxic activities of tumor-infiltrating lymphocytes and draining
      lymph node cells against inoculated tumor cells were significantly increased by
      the therapy. Cytotoxic memory T cells were also induced. The same therapy was
      also applied to SCCV II-bearing C3H/HeJ mice in which the Toll-like receptor
      (TLR) 4 is mutated; no immunotherapeutic effect was observed in the mice. These
      findings suggest that local DC therapy in combination with TS-1 and OK-432 may
      well be a useful strategy for the treatment of solid tumors, and that TLR4
      signaling is involved in the success of this therapy.

PMID- 15553666
TI  - [Experimental study for a combination chemo-immunotherapy using dendritic cells].
AB  - This study was designed to seek for the optimal anticancer agents for a
      combination of chemotherapy and specific immunotherapy using dendritic cells (DC)
      in gastric cancer. We investigated the immuno-suppressive activity of anticancer
      agents on human peripheral blood mononuclear cells (PBMC), apoptosis inducing
      activity on gastric cancer cells and expression of Toll-like receptor (TLR)-4
      mRNA on immatureDCs (iDCs) by paclitaxel (TXL) and docetaxel (TXT). We further
      compared the cytotoxicity of cytotixic T lymphocytes (CTLs) induced by DCs pulsed
      with tumor cell lysate and apoptotic cells induced by TXT. Although most of the
      anticancer agents demonstrated the suppression activity on proliferation of PBMC
      in a dose dependent manner, TXT, doxifluridine and irinotecan did not show the
      suppressive activity on PBMC even in the highest drug concentration. About 60% of
      gastric cancer cells demonstrated apoptosis after a 24-48 hour treatment with
      both TXL and TXT. Expression of TLR-4 mRNA in iDCs was up-regulated by TXT, not
      by TXL, and peaked at 2 hours after the treatment. CTLs induced by DCs pulsed
      with tumor cell lysate and apoptotic cells showed a similar killing activity to
      target cells. These results suggest that TXT appears to be an optimal anticancer
      agent for a combination therapy with chemotherapy and tumor specific
      immunotherapy using dendritic cells in gastric cancer.

PMID- 15553667
TI  - [Anti-apoptosis protein, survivin-2B-derived peptide vaccine therapy].
AB  - As advances in new therapeutic modalities are urgently needed, one of which is
      tumor-specific immunotherapy. We identified an HLA-A24-restricted antigenic
      peptide, survivin-2B80-88, and started a phase I clinical study of survivin-2B
      peptide vaccination in patients with advanced or recurrent colorectal cancer. Of
      15 patients who finished receiving the vaccination schedule, three suffered
      slight toxicities. In 6 patients, tumor marker levels decreased transiently
      during the period of vaccination. Slight reduction in tumor volume was observed
      in one patient, which was considered a minor responder. Analysis of peripheral
      blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an
      increase in peptide-specific CTL after vaccination. This phase I clinical study
      revealed that administration of the survivin-2B peptide is safe. The vaccination
      with survivin-2B peptide alone was not enough to elicit clinical responses.
      Consequently, we have recently started the second clinical study of survivin-2B
      peptide vaccine in combination with various adjuvants.

PMID- 15553668
TI  - [Immunotherapeutic reactivity of dendritic cells loaded with a variety of antigen
      preparations].
AB  - The findings summarized here provide a direct comparison of the immunogenicity of
      various DC loading strategies included pulsing with protein, peptide, tumor cell
      lysate, irradiated tumor cells and electrofusion of DCs and tumor cells. For the
      treatment of 3-day established pulmonary metastases, electrofusion of DCs and
      tumor cells generated a therapeutic vaccine far superior to other methods of DC
      loading. Consistent with their therapeutic activity, fusion hybrids stimulated
      the release of the largest amount of interferon-gamma from immune T cells.
      However, IL-10 secretion did not correlate with in vivo therapeutic reactivity.
      In conclusion, DC-tumor fusion hybrids were the most effective vaccine to
      eradicate existing tumors. These data support the use of DC-tumor electrofusion
      cells for the treatment of human cancer.

PMID- 15553669
TI  - [Reduction of immunosuppression and shift to Th1 response by tumor-DC (dendritic
      cells) fusion vaccine].
AB  - Immunotherapy with tumor-dendritic cells (DC) fusion vaccine has been shown to
      induce an immune response against multiple tumor antigens including unknown tumor
      antigens. In this study, we examined immunological changes by tumor-DC fusion
      vaccine. Nine patients with advanced or recurrent gastrointestinal cancer that
      was unresponsive to standard surgical therapy and chemotherapy were enrolled in
      this study after informed consent was obtained. Monocytes were separated from the
      peripheral blood collected by leukapheresis, and were cultured with GM-CSF and IL
      4 for 6 days. Then, TNF-alpha, IL-1beta, IL-6 and PGE2 were added for maturation
      of DC. Fusion of irradiated tumor cells and DC was created by polyethylene glycol
      and electroporation. The fusion vaccine was injected subcutaneously into the
      inguinal region four times every two weeks. There were no adverse effects or
      autoimmune responses after vaccination in any patients. The clinical response was
      stable in five patients, and disease progression in four patients. Delayed skin
      tests changed to positive in six of the nine patients after vaccination. IAP
      levels decreased in five patients and TGF-beta levels decreased in six patients.
      Th1/Th2 and Tc1/Tc2 balances improved in six of the nine patients after
      vaccination. In this study, it was shown that immunosuppressive factors, such as
      IAP and TGF-beta, and Th1 balance are useful as markers of immunomonitoring for
      tumor-DC fusion vaccine in patients with advanced or recurrent gastrointestinal
      patients.

PMID- 15553670
TI  - [Life-prolonging effect of immunocell BAK (BRM activated killer) therapy-
      evidence based integrative medicine].
AB  - We devised an innovative type of immunocell therapy called biological response
      modifier (BRM)-activated killer (BAK) therapy, which utilizes most of non-MHC
      (major histocompatibility complex)-restricted lymphocytes, CD56-positive cells
      including gammadelta T cells and NK cells. CD56-positive cells are neuro-immune
      endocrine (NIE) multifunctional, integrated cells. We enrolled 30
      immunosuppressed patients whose immunosuppressive acidic protein (IAP) levels in
      serum were over 580 microg/ml, and 63 immunoreactive solid cancer outpatients
      whose IAP level in serum were under 580 microg/ml. Treated with BAK therapy, the
      mean survival time of immunosuppressed patients was 5.0 months. On the other
      hand, survival time of immunoreactive advanced postoperative patients (stage IV)
      and inoperable lung cancer patients (stage IIIb) was 27.1 months. BAK therapy has
      a life-prolonging effect without any adverse effects and maintains satisfactory
      quality of life (QOL) for advanced solid cancer patients. Based on this evidence,
      we propose what can be called Integrative medicine which is neither Western nor
      Chinese medicine.

PMID- 15553671
TI  - [Long-term prognosis of hepatocellular carcinoma patients treated with adoptive
      immunotherapy].
AB  - Adoptive immunotherapy was performed for patients with multiple hepatocellular
      carcinoma (HCC) using LAK cells via the hepatic arterial catheter. One case
      study: A 45-year-old male patient was performed an absolute-non-cure operation.
      The operation was a success. However, some residual tumors remained in the liver.
      After the operation, adoptive immunotherapy was performed for 7 times in 5 weeks.
      The total inoculated LAK cells were 6.9x10(9). After the adoptive immunotherapy,
      no residual tumors were detected in the liver. He survived for 7 years in
      remission. Our results show that adoptive immunotherapy with LAK cells is useful
      and effective for patients with multiple HCC.

PMID- 15553672
TI  - [The repetitive immune cell transfer therapy combining non-myelosuppressive
      chemotherapy for patients with advanced and refractory cancer].
AB  - Autologous tumor cells stimulated with T lymphocytes (AuTL) were generated ex
      vivo from peripheral blood lymphocytes over a two-week co-culturing process with
      autologous tumor cells. These AuTLs were capable of lysing established tumor cell
      lines and may have a potential for efficacy as an adoptive immunotherapy (IT) in
      advanced and metastatic refractory cancer patients (pts). We investigated the
      feasibility of a combination of AuTL transfer and chemotherapy (ChT) based on the
      conventional conditioning regimen in order to take advantage by both the
      anticancer effects and reconstruction of antitumor immunity. Nineteen patients
      were enrolled in a pilot clinical trial. The two administrations of AuTL were
      given prior to chemotherapy (ChT) for one treatment cycle. The treatment was
      repeated at least for three cycles over a one-week interval. The conventional ChT
      regimen was based on the standard dosage. The pts consisted of 3 of gastric
      cancer, colon cancer, lung adenocarcinoma, respectively, 6 of esophageal cancer,
      and 2 of breast and pancreas carcinoma, respectively. AuTLs were administered
      1x/2 weeks using direct injection or intraarterial infusion. The median duration
      of the treatment was over 11.5 months, and the median survival time was 14.8
      months. Adverse events related to both the ChT and AuTL transfers at all dosages
      were minimal. Four of the 13 pts achieved major tumor responses (2 CR: complete
      regression and 2 PR: partial regression) in this study. Three pts showed
      progressive disease, and 6 pts had stable disease for over 90 days. PBMC were
      evaluated for cytokine production prior to the treatment and after 3 treatments.
      Two and one of 4 CR/PR pts had increased IFN-gamma and TNF-alpha production with
      no TGF-beta1 responses by their PBMC after 3 treatments, respectively. Two out of
      6 pts who experienced stable disease after the treatment had high IFN-gamma and
      TNF-alpha responses and no TGF-beta1 or IL-4 response. TGF-beta1 and IL-4
      secretion increased in parallel in 3 out of 3 pts that experienced progressive
      disease after the treatment. These data show that combination therapy of AuTL
      transfer and non-myeloablative ChT is a feasible option for patients with
      refractory advanced cancers without serious adverse events and without reducing
      Th1 cytokine responses in peripheral blood for most of the pts that responded to
      the treatment. According to each mechanism of IT and ChT, a more stringent
      evaluation of AuTL transfer combined with non-myeloablative ChT for various kinds
      of cancers should be performed to manage the immunodeficiency in the pts with
      advanced cancer and to improve the effect of antitumor AuTLs.

PMID- 15553673
TI  - [Variation of cytokines with administration of chemotherapeutic and immuno
      therapeutic drugs for colorectal cancer].
AB  - Systemic and local immunological responses were studied in patients with or
      without preoperative administration of chemotherapeutic and/or immunotherapeutic
      drugs for colorectal cancer. The plasma TGFbeta and other cytokines such as IL-2,
      IL-4, IL-6, IL-10, IL-12, IFN-gamma in the supernatant fluid of culture of
      peripheral blood mononuclear cell (PBMC) and regional lymph node were measured by
      the ELISA method. A systemic response of cytokines was as follows: the production
      of plasma TGFbeta increased in many cases by chemotherapeutic drugs with a
      significant elevation of the mean production. Productions of IFN-gamma, IL-2, IL
      12 in the supernatant fluid of culture of PBMC increased in many cases by
      immunotherapeutic drugs, and that of IL-4, IL-6 increased in many cases by
      chemotherapeutic drugs. A local response of cytokines was as follows: the
      production of IL-2 by immunotherapeutic drugs was greater than that without
      immunotherapeutic drugs whereas the production of IL-10 by immunotherapeutic
      drugs was smaller than that without immunotherapeutic drugs.

PMID- 15553674
TI  - [Combined cell therapy by using dendritic cells, T-cells and NK cells to human
      polymorphic cancer].
AB  - Although an expression of MHC molecules and tumor associated antigens of the
      cancer are not uniform, we consider that the cancer immunotherapy for some
      specific tumor antigens cannot correspond to molecular biological varieties of
      the cancer. Consequently, we tried to develop a method to separate dendritic
      cells (DC), T-cells and natural killer (NK) cells from peripheral blood
      mononuclear cells (PBMC) obtained from healthy volunteers. PBMC were separated by
      centrifugation on Ficoll-Hypaque gradients from peripheral blood obtained from
      healthy volunteers. After separating these cells, the cells were put into a
      plastic flask, and we isolated monocyte fraction (dendritic cells), NK cell
      fraction and T-cell fraction one after another by the difference in its ability
      to adhere to a plastic flask. We analyzed surface markers and activation states
      of these groups. We could induce dendritic cells from the monocyte fraction, CD3
      activated T-cells (CAT) from the T-cell fraction, and adherent lymphokine
      activated-killer cells (A-LAK) from the NK cell fraction. Therefore, we indicate
      the possibility of the combined cell therapy with three immune cell fractions in
      which we can induce from the same blood at once.

PMID- 15553675
TI  - [The long-term results of hepatic resection for metastatic lesions from
      colorectal cancer].
AB  - We reviewed the clinical course of 51 patients who underwent hepatic resection
      for metastatic lesions from colorectal cancer between January 1984 and December
      1997. The cumulative survival rate at 3 and 5 years were 57% and 43%,
      respectively. Sex, age, chronology of liver metastases (LM), number of LM,
      maximum diameter of LM, macroscopic surgical resection margin, type of hepatic
      resection, chemotherapy after hepatic resection, and site of primary tumor were
      not found to be statistically significant prognostic factors. The presence of
      lymph node metastases for the primary tumor was a predictor of shorter survival
      duration by univariate analysis (p=0.03). Recurrence was not observed in 15
      patients. However, recurrence was observed in 36 patients, of which 4 were in
      remission by undergoing repeated resection for recurrence sites (2 were in lung,
      2 were in liver). Although the long term survival of the 19 patients with no
      significant remarks to be noted, but no one survived with more than 4 hepatic
      metastases among the long term survivors.

PMID- 15553676
TI  - [A case of the 5-year survivor of ascending colon cancer associated with
      synchronous multiple liver metastasis and peritoneal dissemination successfully
      treated with combination therapy of systemic and hepatic arterial infusion
      chemotherapy].
AB  - A 67-year-old woman was diagnosed by a series of examinations as having ascending
      colon cancer with synchronous multiple liver metastasis. She underwent an
      operation after the PTPE (percutaneous transhepatic portal vein embolization) to
      the right lobe of the liver, as we considered that the metastatic liver tumors
      were all resectable. In the surgery, we identified seven peritoneal tumors and a
      lymph node swelling. We then pathologically diagnosed them as being peritoneal
      dissemination (p3) and lymph node metastasis (n2(+)). Therefore, hepatectomy was
      not performed, but the right hemicolectomy (D2) and insertion of an arterial
      infusion catheter into the hepatic artery were performed. In addition, all seven
      peritoneal tumors were resected. After being discharged from hospital, she was
      treated as an outpatient with the combination chemotherapy of systemic
      intravenous administration (5-fluorouracil or 5-FU, 2,500 mg/month) and hepatic
      arterial infusion (5-FU, 1,500 mg/week) for 16 months. Then, she continued to
      take tegafur uracil (300 mg/day) by mouth for 39 months. The metastatic liver
      tumors were gradually reduced and resulted in complete response (CR) for 20
      months after the operation. She has been in remission for the past 5 years
      without recurrence. During the treatment, we noticed a complete atrophy that was
      sustained in the right lobe of the liver to which PTPE was performed. As far as
      hepatic arterial infusion chemotherapy is concerned, our case study was
      interesting and effective.

PMID- 15553677
TI  - [Two cases of resection of synchronous bilobar multiple liver metastases from
      colorectal cancer after hepatic arterial infusion chemotherapy].
AB  - We report 2 cases of synchronous bilobar multiple liver metastases from
      colorectal cancer which are hepatectomised following a hepatic arterial infusion
      chemotherapy. Both cases were considered unresectable metastases before
      chemotherapy. Case 1: A 55-year-old male, with rectal cancer and multiple hepatic
      metastases, was performed a low anterior resection. Hepatic arterial infusion
      chemotherapy (5-FU 1 g/m2 5h qw) and systemic chemotherapy (5-FU/LV) were
      administered. Twelve months after the first surgery, hepatectomy was performed.
      Case 2: Right hemicolectomy was performed on a 66-year-old male, with cancer of
      the transverse colon and multiple hepatic metastases. Hepatic arterial infusion
      chemotherapy was administered 38 times. Thirteen months after the first surgery,
      hepatectomy and MCT were performed. Even among the cases of unresectable hepatic
      metastases from colorectal cancer, there are some in which resection is possible
      followed by hepatic arterial infusion chemotherapy. Re-evaluation for hepatectomy
      is needed for the cases where hepatic arterial infusion chemotherapy is
      administered.

PMID- 15553678
TI  - [Successful treatment of liver metastasis and extrahepatic metastasis with
      hepatic arterial infusion of CDDP, CPT-11, and 5-FU].
AB  - A 63-year-old man, who had been operated with right hemicolectomy 1 year and 3
      months ago, had giant liver metastasis, lung metastasis, and local dissemination
      tumor due to ascending colon cancer. He was treated by systemic chemotherapy with
      5-FU and the treatment evaluation was PD on CT. After admission to our hospital,
      he was treated by hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5
      FU. After 3 courses of the treatment, each recurrent lesion decreased on CT and
      the CEA level decreased. There were no side effects except mild diarrhea. We
      believe hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU may be
      an effective strategy against liver metastasis and extrahepatic metastsis due to
      colon cancer.

PMID- 15553679
TI  - [Two case reports of complete regression of liver metastases from colorectal
      cancer after locoregional immunochemotherapy].
AB  - Hepatic arterial infusion (HAI) with pharmacokinetic modulating chemotherapy
      (PMC) has been well known to be one of the most effective protocols for
      unresectable liver metastases from colorectal cancer. PMC is a combination of
      oral UFT and continuous hepatic arterial 5-FU infusion. We present herein the
      cases of two patients with multiple liver metastases from colorectal cancer in
      whom complete regression (CR) was achieved by HAI with PMC in combination with
      Lentinan (immunostimulator). These patients received HAI via an implantable port
      system with a 4-24-hour continuous perfusion of 5-FU at 1,000 mg/m2 plus Lentinan
      at 2 mg/body once a week, and oral administration of UFT at 200-300 mg/m2/day
      everyday. CR of all metastatic lesions in the liver was achieved 4 months after
      the initiation of the treatment in both patients. One patient maintained CR for 3
      months, but he died due to a recurrence of liver metastases and peritoneal
      dissemination 19 months after the initiation of the treatment. The other patient
      has been well without recurrence for 21 months. Because the liver is the largest
      immunologic organ, Lentinan could have activated lymphocytes and macrophages in
      the liver. Judging from the clinical experience of these two cases, HAI with PMC
      in combination with Lentinan could be one of the most promising treatment
      strategies for unresectable liver metastases from colorectal cancer.

PMID- 15553680
TI  - [A case of liver metastasis of gastric cancer responding well to TS-1].
AB  - We report the case of a 79-year-old female with gastric cancer accompanied by
      liver metastasis that was successfully treated by TS-1, a novel oral
      fluoropyrimidine derivative. Abdominal CT scan showed a low-density area in the
      lateral segment of the liver and lymph node swelling in the right side of the
      abdominal aorta. One treatment course consisted of 4 weeks of TS-1 administration
      (100 mg daily) followed by a 2-week break. After 2 courses of this treatment, an
      abdominal CT scan showed no evidence of liver metastasis and a reduction of lymph
      nodes metastasis. The serum level of CA19-9 was reduced from 780 U/ml to within a
      normal range. Grade 1-2 toxicity (nausea and diarrhea) was seen after 2 courses.
      We conclude that TS-1 may be beneficial in the treatment of the liver metastasis
      of gastric cancer.

PMID- 15553681
TI  - [Gastric cancer with liver metastasis effectively treated by intra-hepatic
      arterial infusion].
AB  - The prognosis of gastric cancer with liver metastasis is very poor. Because many
      gastric cancers with liver metastasis have multiple metastatic tumors in the
      liver, and the indication for surgical resection is rare. Moreover, the non
      curative factors of many cases are not only liver metastasis but also are lymph
      node metastasis and peritoneal dissemination. However, some authors have reported
      gastric cancer with liver metastasis was treated effectively by intra-hepatic
      infusion of an anti-cancer drug. In this article, we report three cases of
      gastric cancer with liver metastasis that are treated effectively by intra
      hepatic arterial infusion of an anti-cancer drug. There were no non-curative
      factors except liver metastasis. The first was a H3 case treated effectively by
      intra-hepatic arterial infusion of 5-fluorouracil (5-FU), mitomycin C (MMC) and
      peroral administration of 5-FU. The metastatic liver tumors had disappeared in 14
      weeks. However, the patient eventually died of liver and brain metastases in 7
      months after the therapy. The second was a H2 case treated effectively by intra
      hepatic arterial infusion of CDDP and peroral administration of 5'-DFUR and PSK.
      The metastatic liver tumors had disappeared in 4 months, and the patient is still
      alive without recurrence in 35 months after surgery. The third was a H2 case
      treated effectively by intra-hepatic arterial infusion of cisplatin (CDDP) and
      peroral administration of TS-1 and PSK. The size of metastatic nodules had
      increased, and Virchow lymph node metastasis had appeared in 28 months after
      surgery. The patient eventually died in 32 months after surgery. These results
      suggested that intra-hepatic arterial infusion of CDDP with peroral
      administration of TS-1 or 5'-DFUR was an effective therapy for gastric cancer
      with liver metastasis.

PMID- 15553682
TI  - [A case of gastric cancer with extraordinary liver metastasis effectively treated
      by adjuvant chemotherapy].
AB  - This was an extraordinary liver metastasis case with complication when the
      patient, a 70-year-old male, was diagnosed with stomach cancer for the first
      time. However, the patient has been in remission and is a long-term survivor due
      to an active chemotherapy after the operation. His chief complaints were
      stomachache and a loss of weight. He was diagnosed with stomach cancer by
      endoscopy. During the surgery, the mass was found to be 3 QFB palpable caused
      from hepatomegaly. The liver dysfunction was revealed in the blood biochemistry
      inspection. The abdominal CT revealed that the stomach cancer had spread to the
      whole liver. Distal gastrectomy was performed on May 22, 1997. In pathological
      findings, the tumor was diagnosed as a well-differentiated adenocarcinoma. Final
      findings: M, type3, T3 (SE), N2, H3, P0, CY0, and Stage IVb. The 5-FU based
      chemotherapy was performed and a complete response was temporarily obtained.
      However, it has recurred one year later and two or more kinds of chemotherapy
      have continued. He is alive for more than 7 years and comes to our hospital as an
      outpatient.

PMID- 15553683
TI  - [A case report of the 8 year survivor--unresectable liver metastases from
      advanced gastric cancer (Stage IV) were completely responsive, after 4 years from
      a total sequential gastrectomy, combining docetaxel treatment to regress the
      recurrence].
AB  - This case was a 69-year-old male who had advanced gastric cancer with
      unresectable multiple liver metastases (Stage IV). He received a combination
      therapy consisting of a continuous venous infusion (cisplatin: CDDP 10 mg/body, 5
      FU 500 mg/body, day 1-28). As a result, metastatic tumors in the liver completely
      disappeared and a total gastrectomy was sequentially performed. Four years after
      the surgery, neck lymph node (LN) metastases and the right adrenal metastasis
      appeared, and chemotherapy (TS-1, and sequentially TS-1+CDDP) was performed. But,
      the chemotherapy to eradicate the metastases was hardly enough to be effective.
      Next, docetaxel (DOC 60 mg/m2 q3w) was started. After 9 courses, they were
      effective and marked regressions (70%). A total of 15 courses of docetaxel
      administration were possible until tumor progression recurred. This regimen was
      not severe in toxicity for the duration except for grade 3 poor appetite.
      Docetaxel will be a key drug for the gastric cancer. In case of responding well
      to the chemotherapy, we can hope for an extended long-term survival with a
      continuation of this regimen.

PMID- 15553684
TI  - [Three successful case reports of advanced gastric cancer with chemotherapy].
AB  - We report three successful cases with continuous systemic chemotherapy for
      advanced gastric cancer. Case 1: A 67-year-old male with gastric cancer.
      Abdominal CT showed the invasion in the pancreas and as a result, continuous
      systemic infusion of low-dose cisplatin (CDDP 20 mg/day) and 5-fluorouracil (5-FU
      1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was
      continued for 5 days and discontinued for 25 days. Three months after the
      chemotherapy, the main tumor was remarkably reduced (downstaging was obtained),
      and consequently, total gastrectomy was performed. Case 2: A 78-year-old male
      with gastric cancer and hepatic multiple metastases. Abdominal CT scan before
      operation did not reveal the hepatic metastasis. In the operation for distal
      gastrectomy, we found multiple metastases on the surface of the liver. Continuous
      systemic infusion of low-dose CDDP (20 mg/day) and 5-FU (1,000 mg/day) was
      performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days
      and discontinued for 2 days. One month after the chemotherapy, Liver metastases
      had almost disappeared. Case 3: A 73-year-old male had received a distal
      gastrectomy based on the diagnosis of gastric cancer. The tumor marker, CA19-9,
      immediately decreased after the operation, but had increased again. He was
      treated with a combination chemotherapy of TS-1 and CDDP. The treatment consisted
      of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. CDDP
      of 10 mg/day was infused intravenously (day 1-5). Four weeks after the infusion,
      CA19-9 had returned to almost normal. We conclude that the combination
      chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for
      advanced and metastatic gastric cancer.

PMID- 15553685
TI  - [A case responding to weekly paclitaxel therapy as second-line chemotherapy for
      gastric cancer previously treated with TS-1].
AB  - A 58-year-old male patient with the recurrence of para-aortic lymphnodes after TS
      1 treatment was treated by a weekly infusion of paclitaxel as second-line
      chemotherapy. Paclitaxel was administered at a weekly dose of 70 mg/m2/day for
      three weeks followed by a one week interval. After 2 courses, the tumor was
      reduced, and the reduction was judged as PR. Moreover, after 5 courses, the tumor
      was more remarkably reduced and the reduction was judged as CR. The grade 2
      leukopenia, neutropenia, and grade 1 alopecia were observed as adverse events.
      Recently, we treated 11 patients of advanced or recurrent gastric cancers with
      measurable lesions, using the weekly paclitaxel therapy after TS-1 treatment. The
      response rate was 36.4%. The median duration of PR was 130 days. Therefore, a
      weekly paclitaxel regimen was considered to be one of the promising regimens for
      advanced or recurrent gastric cancer as the second-line chemotherapy after TS-1
      treatment.

PMID- 15553686
TI  - [Usefulness of F-18-fluorodeoxyglucose positron emission tomography for
      evaluating the efficacy of transient hepatic arterial chemoembolization for liver
      metastases of rectal cancer--a case report].
AB  - It is pointed out that there can be a discrepancy between the effect diagnosed by
      radiographic imaging and that by histological examination, when we treat patients
      with liver metastases of colorectal cancer by a transient hepatic arterial
      chemoembolization. We report a case of liver metastases of rectal cancer in which
      F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for
      evaluating the therapeutic efficacy for transient hepatic arterial
      chemoembolization. A 58-year-old man with synchronous liver metastases (H2) of
      rectal cancer underwent a low anterior resection, a partial hepatectomy,
      cholecystectomy, and ligation of the gastroduodenal artery. After these
      operations, the patient received 6 hepatic arterial injections with degradable
      starch microspheres (300-600 mg), adriamycin (30 mg), and mitomycin C (10 mg) for
      the remaining metastatic lesion (S7). Although abdominal CT scan revealed a
      partial response, FDG-PET did not show any abnormal deposits. Hepatic posterior
      segmentectomy was performed 7 months after the first operation. Histological
      examination did not show any viable tumor cells in the resected specimen.

PMID- 15553687
TI  - [A case of rectal cancer with solitary adrenal metastasis].
AB  - This is the case of a 67-year-old woman with a sudden on-set of lower abdominal
      pain and pre-shock. A physical examination showed signs of pan-peritonitis.
      Emergency was operation performed 5 hours after the onset. She had undergone
      Hartmann's operation for rectal cancer. Six month after the operation, abdominal
      CT scan revealed the mass of puriform acites, about 20 mm in diameter, in the
      right suprarenal region. Right adrenalectomy was performed with a diagnosis of
      solitary adrenal metastasis from rectal cancer. Histologically, the metastatic
      adenocarcinoma was moderately differentiated to the adrenal medulla. The capsule
      was kept intact, and no swelled lymph nodes were found around the adrenal gland.
      There have been no signs of recurrence for 4 years after the operation.

PMID- 15553688
TI  - [Case report--Complete response of liver metastasis of rectal cancer after
      combination chemotherapy of CPT-11 + UFT-E].
AB  - A 54-year-old man underwent abdominoperineal resection for rectal cancer.
      Adjuvant chemotherapy was not performed because of stage I cancer. Nine months
      after the operation, solitary liver metastasis, and elevated CEA and CA19-9, were
      found during the postoperative work-up. A combination chemotherapy of CPT-11 and
      UFT-E was performed before scheduled liver resection. 150 mg/m2 of CPT-11 was
      administered on days 1 and 15. 375 mg/m2/day of UFT-E was divided in half and
      administered on days 3-7, 10-14, 17-21, and 24-28 as one course of treatment.
      This regimen was repeated every 5 weeks. The patient had a grade 2 diarrhea and
      nentropenia during the treatment. Bowel obstruction was also observed after 5
      courses of treatment, which required hospitalization. In addition, the liver
      metastasis had disappeared. There was no evidence of recurrence after 8 months of
      chemotherapy. It was suggested that CPT-11+UFT-E combination chemotherapy was
      effective for advanced colorectal cancer.

PMID- 15553689
TI  - [Successful hepatic arterial infusion therapy of CDDP/5-FU/IFN-beta3 for
      recurrent hepatocellular carcinoma].
AB  - A 52-year-old male patient was admitted to our hospital for a further examination
      of liver tumor. He was positive for hepatitis C virus antibody. CT scanning
      revealed two hyper vascular tumors at the lateral segment of the liver and
      another one located at segment 8, an indication of hepatocellular carcinoma
      (HCC). Ascites were not detected and major serological findings were T-Bil 1.1
      mg/dl, Alb 3.5 g/dl, ICG R15 12% and PT 88%. Lateral segmentectomy and a partial
      resection of the segment 8 were performed at the same time. An insertion of
      catheter in hepatic artery via gastroduodenal artery was carried out.
      Dehydropyrimidine dehydrogenase (DPD) activity of the tumor was 157 pmol/min/mg
      proteins. Recurrence was detected one year after the operation at segments 4 and
      8. Arterial infusion chemotherapy using CDDP (10 mg), 5-FU (1,000 mg) and IFN
      beta 3MU (continuous infusion for 5 days) was started two months later, and a
      complete response was achieved. The chemotherapy continued as long as severe
      adverse effects were not observed. However, two months after the tumor
      disappearance, the treatment discontinued due to occlusion of the infusion
      system. Recurrence occurred in two months at the same location where the previous
      tumor was. In conclusion, these results suggest that arterial chemotherapy using
      CDDP/5-FU/IFN-beta against HCC may be beneficial.

PMID- 15553690
TI  - [A case of successful treatment with combined 5-fluorouracil, adriamycin,
      cisplatin (FAP) therapy followed by Gemcitabine, UFT therapy and intra-arterial
      FAP therapy for unresectable advanced gallbladder cancer].
AB  - The prognosis of unresectable advanced gallbladder cancer is extremely poor. We
      presented a 61-year-old female with unresectable advanced gallbladder cancer who
      received FAP therapy, Gemcitabine + UFT therapy, and an intra-arterial FAP
      therapy that followed. She is still alive 18 months after the first diagnosis. It
      may be possible to improve the prognosis by maintaining QOL using the combination
      of chemotherapies such as FAP, Gemcitabine, and UFT.

PMID- 15553691
TI  - [Successful treatment for advanced cholangiocellular carcinoma with intrahepatic
      metastasis and/or portal vein tumor thrombi by intraarterial chemotherapy
      combined with 5-fluorouracil, adriamycin and cisplatin (FAP)--two cases report].
AB  - The patients of unresectable cholangiocellular carcinoma (CCC) have extremely
      poor prognosis. Case 1 was a 72-year-old male who had CCC in the left lobe of
      liver with intrahepatic metastasis. From June 2003, he received hepatic arterial
      infusion chemotherapy (FAP: 5-fluorouracil 250 mg/day continuous infusion, day 1
      5, adriamycin 10 mg/day, day 1, and CDDP 10 mg/day, day 1). After 5 courses,
      abdominal CT revealed that the main tumor had regressed. Case 2 was a 66-year-old
      male who had CCC with portal vein tumor thrombus of anterior branch (Vp2). He
      received FAP arterial infusion chemotherapy that was a same regimen as with the
      case 1 patient. After 5 courses were administered, Abdominal CT revealed that the
      size of the main tumor at S8 had not changed, and that portal vein tumor thrombus
      had disappeared. In both cases, there was no complication related to the
      chemotherapy. They are alive for more than 1 year after chemotherapy had started.
      FAP hepatic arterial infusion chemotherapy might be promising as an effective
      therapy for non-resectable CCC without extra hepatic metastasis.

PMID- 15553692
TI  - [MTX/CDDP/5-FU double modulation intra-peritoneal chemotherapy for advanced and
      metastatic gastric cancer--comparison with intra-aortic route and intra-venous
      route].
AB  - We studied the efficacy of MTX/CDDP/5-FU intra-peritoneal chemotherapy for
      advanced and metastatic gastric cancer (n=24), and compared the results with
      intra-aortic (n=26) and intra-venous (n=21) routes of MTX-CDDP-5-FU double
      modulation therapy. I.p. administration was more efficient for reduction of
      malignant acites (p=0.049). However, median survival duration of malignant acites
      cases showed no difference between the i.p. group and i.a., i.v. groups
      (p=0.103). Survival rate of the i.p. group was no different with those of i.a.
      and i.v. groups (p=0.36). Frequency of side effects is much lower in the i.p.
      group.

PMID- 15553693
TI  - [The significance of low-dose CDDP intraperitoneal administration for cases of
      peritoneal dissemination of gastric cancer].
AB  - We examined the significance of low-dose cisplatinum (CDDP) intraperitoneal
      administration for cases of peritoneal dissemination of gastric cancer. Sixty
      eight cases of gastric cancer, diagnosed as P1 or CY1 in the gastrectomy
      operation that was carried out during the period between January 1994 and
      December 2001, were studied based on accumulated survival rate and mean survival
      time (MST). Ten milligram of CDDP was weekly administrated intraperitoneally
      through an infusion port. A two-week interval was taken after the eight-week
      administration. This group, the CDDP intraperitoneal administration group, was
      statistically superior both in the accumulated survival rate and MST. These
      results suggested that the low-dose CDDP intraperitoneal administration would
      contribute to improved prognosis of such gastric cancers as P1 or CY1.

PMID- 15553694
TI  - [Effects of repeated intraperitoneal CDDP chemotherapy for the prevention of T3
      and T4 gastric cancer].
AB  - We studied the significance of repeated intraperitoneal CDDP administration, as
      adjuvant chemotherapy, for the prevention of T3 and T4 gastric cancer. Fifty-two
      patients who had been operated as Curability B were divided into the following
      two groups, and the data on survival rate, median survival time and interval of
      "free of recurrence" were accumulated and analyzed. Group A consisted of nineteen
      patients treated with intraperitoneal CDDP administration and oral anticancer
      drugs. Group B were treated with systemic chemotherapy. Group A was superior to
      Group B in comparing the analyzed data. These results suggested that repeated
      intraperitoneal CDDP chemotherapy for the prevention of T3 and T4 advanced
      gastric cancer would improve survival rate.

PMID- 15553695
TI  - [Treatment results of peritoneal dissemination from gastric cancer by neoadjuvant
      intraperitoneal-systemic chemotherapy].
AB  - No standard treatment exists for peritoneal dissemination from gastric cancer. We
      reviewed our experience using a novel treatment consisting of peritonectomy and
      intraoperative chemo-hyperthermic peritoneal perfusion (CHPP). Records of all
      patients who underwent CHPP and cytoreductive surgery from 1992 to 2001 were
      reviewed. RESULTS: Data from 107 patients (average age, 52 years) were available.
      P3 dissemination was found in 72 patients, and 8 and 27 patients showed P1 or P2
      dissemination, respectively. Peritoneal metastasis was synchronous in 75 and
      metachronous in 32 patients. All patients received CHPP after cytoreductive
      surgery. Peritonectomy was performed in 42 patients. Complete cytoreduction (CC
      0) was achieved in 47 patients (44%). Peritonectomy, resulted in CC-0 in 69%
      (29/42), but CC-0 was achieved in 18 of 65 (28%) patients by ordinary surgical
      techniques. There were 23 postoperative complications (21%) after operation. The
      overall operative mortality was 2.8% (3/107). Median follow-up for the entire
      study group was 46 months. Seventeen patients (15%) were disease-free, and 90
      patients were dead at the time of analysis. Eighty-seven deaths were related to
      progression of disease. The median survival of all patients was 16.2 months, with
      an actual 5-year survival of 6%. Median survival of CHPP plus ordinary
      cyoreduction was 12.0 months and that after CHPP and peritonectomy was 22.8
      months. Completeness of cytoreduction and peritonectomy were significant
      prognostic factors on univariate analysis and 5-year survival rate was 27%. Lymph
      node status, grade of peritoneal dissemination (P1-2 vs P3), age (>60 years vs
      <60 years), tumor volume of dissemination (>2.5 cm vs <2.5 cm in diameter), and
      histologic type (differentiated vs. poorly differentiated type) did not affect
      survival. The cox proportional model demonstrated that completeness of
      cytoreduction was the strongest prognostic factor. Patients who had an incomplete
      resection had 2.8-fold higher risk of dying from disease than patients who
      underwent complete cytoreduction. The 5-year survival after complete
      cytoreduction was 12%, compared with 2% for incomplete resection. Four patients
      lived more than 5 years. Cytoreduction was incomplete in one 5-year survivor who
      showed complete response to CHPP. CONCLUSION: Complete cytoreduction using
      peritonectomy and CHPP may improve survival of patients with peritoneal
      dissemination from gastric cancer. This procedure is most appropriate for highly
      motivated patients who are committed to survive as long as possible.

PMID- 15553696
TI  - [Evaluation of hepatic artery infusion chemotherapy for liver metastasis of
      colorectal cancer using a side-hole catheter].
AB  - In our department forty cases of hepatic artery infusion chemotherapy using a
      side-hole catheter were analyzed with liver metastasis of colorectal cancer from
      December 2000 to December 2003. This easily placed catheter is able to inject the
      agent effectively from the side hole. The efficacy of high dose 5-FU (1,000
      mg/m2/week) of hepatic artery injected chemotherapy was evaluated. The catheter
      was inserted from femoral or the left subclavian artery, and the side hole
      positioned at the base of proper hepatic artery or common hepatic artery. This
      method resulted in catheter trouble only 18% of the time. As for arterial
      infusion chemotherapy, system management and an evaluation of the drug
      distribution is essential. The one-year survival rate was 71.9%, the 50% survival
      time was 23.4 months, and the response rate was 71%. In conclusion, this therapy
      was effective and useful for hepatic metastasis.

PMID- 15553697
TI  - [A devised method of hepatic and splenic arterial infusion chemotherapy after
      transcatheter peripancreatic arterial embolization for patients with advanced
      pancreatic cancer].
AB  - We previously reported the clinical efficacy based on hepatic and splenic
      arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic
      cancer after transcatheter peripancreatic arterial embolization (TPPAE). However,
      this medical treatment pointed out a few problems in which the method had its
      complexity and a limited use of embolus micro-coil numbers. Then, we tried to
      improve the method in solving those problems. In order to reduce the embolus
      micro-coil numbers for TPPAE, we divided the micro-coil into several parts. We
      also devised the method of HSAIC. We used one catheter with a side hole, so that
      the catheter was able to supply a therapeutic drug for arterial infusion
      chemotherapy, both to the common hepatic artery and splenic artery. The effective
      rate for eleven cases was 72.7%, and there were no significant differences from
      the cases treated with the conventional method of TPPAE-HSAIC. Therefore, the
      devised treatment was considered to be an easy and useful method for TPPAE and
      HSAIC.

PMID- 15553698
TI  - [Radiofrequency ablation combined with transcatheter arterial chemoembolization
      for hepatocellular carcinoma--CT examination during the follow-up period].
AB  - Radiofrequency ablation (RFA) combined with transcatheter arterial embolization
      (TAE) can increase the volume of coagulation necrosis to treat patients with
      hepatocellular carcinoma. Furthermore, in clinical practice, RFA combined with
      TAE using iodized oil and gelatin sponge often induced the sub-segmental or
      segmental necrosis toward the liver periphery of the ablated lesion. In this
      study, we compared the CT findings and histological characteristics of
      peripherally spreading necrosis induced by this combination therapy for 12
      patients with hepatocellular carcinoma. In all cases, complete necrosis of
      ablated lesions and peripherally spreading necrotic areas were confirmed by CT
      examination. The histochemical (lactate-dehydrogenase, maleate-dehydrogenase, and
      NADPH-diaphorase) stained specimens, biopsies from ablated lesions and
      peripherally spreading necrotic areas, were absent suggesting a 100% cellular
      destruction. No incomplete local treatments after the therapy were obtained
      during the 4-26 months of follow-up periods. We conclude that RFA combined with
      TAE using iodized oil and gelatin sponge makes it possible to induce the
      segmental or sub-segmental necrosis including tumors.

PMID- 15553699
TI  - [A case of gastric cancer patient with liver metastasis treated by radiofrequency
      ablation therapy combined with intra-arterial chemotherapy].
AB  - We performed radio-frequency ablation (RFA) therapy combined with intra-arterial
      chemotherapy for a 71-year old female gastric cancer patient with liver
      metastasis. She underwent total gastrectomy due to advanced gastric cancer in
      July of 1996. Because CT scans revealed multiple liver tumors with her, she also
      underwent intra-arterial chemotherapy comprising of 5-fluorouracil, cis-platinum
      and Leucovorin. Although her liver tumors decreased in size and number, after 9
      months, we had to remove the catheter because of hepatic artery obstruction.
      Immediately after the removal, 5 hepatic metastases appeared, which were 3.5 cm
      in maximum diameter. After RFA therapy, CT scans revealed homogenously attenuated
      lesions. Liver biopsy demonstrated a complete coagulation necrosis. She is
      currently alive going into 19 months after liver metastasis and 7 months after
      RFA.

PMID- 15553700
TI  - [Radio-frequency ablation (RFA) assisted endoscopic hepatectomy for
      hepatocellular carcinoma].
AB  - We introduced a new therapeutic approach for hepatocellular carcinoma (HCC);
      Radio-frequency ablation (RFA) assisted endoscopic hepatectomy (RFA-assisted EH).
      Seven patients with HCC, smaller than 3 cm and located on the surface of the
      liver, were entered into this study. RFA on the hepatic cutting line was achieved
      with a 2 cm Cool-tip needle at a 1-cm interval. RFA power was gradually increased
      to 100 W in a minute and ablation was stopped once an impedance-out state was
      attained of RFA power. Hepatic resection was achieved with various items in a
      coagulative hepatic parenchyma. If necessary, additional RFA could be performed
      during the hepatectomy. Patients' characteristics were described as follows;
      average age: 64 years, 5 males and 2 females, liver damage A: 5, B: 2, average
      tumor size: 27 mm, and average tumor number: 1.3 Two thoracoscopic and 5
      laparoscopic approaches were selected. One application of RFA could make an
      elliptical coagulative area (2 cm x 1 cm). RFA was achieved eleven times on the
      hepatic cutting line and three times during the hepatectomy. The average
      operating time and blood loss was 256 minutes and 96 g, respectively. No blood
      product was needed. The average postoperative hospital stay was 11 days and no
      operative complication was encountered. All of the patients were well and without
      recurrence during the observation period (average: 6 months). We positively
      recommend RFA-assisted EH for HCC due to its perfect radicality and safety.

PMID- 15553701
TI  - [The 5-fluorouracil hepato-arterial infusion with oral UFT therapy for the
      hepatic and extra hepatic metastases of colorectal cancer].
AB  - BACKGROUND: The 5 fluorouracil hepato-arterial infusion (5-FU HAI) therapy has a
      good effect on the liver metastases of colorectal cancer. To gain the antitumor
      effect of the extra-hepatic lesion, an oral UFT was combined with 5-FU HAI
      (pharmacokinetic modulating chemotherapy, PMC) to enhance the plasma 5-FU
      concentration. METHODS: UFT (200-400 mg/day) was orally administered daily and a
      continuous infusion of 5-FU (1,000-1,500 mg/5 h) was given once a week. Eight
      patients were treated with this regimen. Five of the eight have extra-hepatic
      lesions with liver metastases when this treatment was started. The response, time
      to progression, survival, and toxicity were detected. RESULTS: Four of the five
      patients with extra-hepatic lesion were evaluated. The response rate was 50% (1
      CR, 1 PR, and 2 SD). For the liver metastases, the response rate was 62.5% (1 CR,
      4 PR, 2 SD, and 1 PD). Grade 2 leukopenia was found in 1 patient. CONCLUSIONS:
      The 5-FU HAI with an oral UFT therapy had a good effect on the extra-hepatic
      lesions as well as hepatic metastases of colorectal cancer.

PMID- 15553702
TI  - [A trial of the new procedure of sentinel node biopsy in the lower rectal cancer
      by a transsacral approach].
AB  - We describe a new method of sentinel node (SN) biopsy in the lower rectal cancer
      by a transsacral approach. Before the operation, an endoscopic clipping was
      performed around the tumor. The patient was placed in a jack knife position. A
      transverse incision was made over the S4-S5 joint. Subsequently, the S4-S5 joint
      was dissected, and the lower rectum was exposed without destroying the perirectal
      fatty tissue. CH-40 dye was injected into the submucosal layer of the rectal
      cancer. The lymph nodes that were blackened within 15 minutes were recognized to
      be SNs. Few investigations were reported with regard to sentinel node navigation
      surgery (SNNS) for lower rectal cancer, because the anatomical properties of the
      lower rectum make it difficult to inject the dye and recognize rectal tumors or
      lymph nodes. In our method, the lower rectum was exposed without destroying the
      perirectal fatty tissue, the dye was easily injected, and the SNs were easily
      found and extirpated. Our method of transsacral approach is considered to be
      useful.

PMID- 15553703
TI  - [Hepatic arterial infusion and occlusion technique for the evaluation of the
      hepatic resection to control the local liver tumor].
AB  - We report 2 cases of metachronous liver metastases from gastric cancer and 1 case
      of hepatocellular carcinoma (HCC) that are treated with a hepatic arterial
      infusion (HAI) to control the progression of local liver tumor. The treatments
      consist of HAI of epirubicin and mitomycin C plus degradable starch microspheres
      (DSM) to achieve temporary vascular occlusions. Hepatic resections were not
      performed in all cases because of the appearance of multiple liver metastases, or
      the hepatic vascular occlusion in 2 cases of gastric cancer, and the liver damage
      in the case of HCC. Therefore, HAI with DSM is useful for the evaluation of the
      hepatic resection in controlling of the local liver tumor.

PMID- 15553704
TI  - [Intra-arterial cellular immunochemotherapy for unresectable pancreatic cancer
      with liver metastasis].
AB  - PURPOSE: To date, no treatment has had a significant impact on pancreatic cancer
      with liver metastasis. We performed locoregional cellular immunochemotherapy for
      unresectable pancreatic cancer with liver metastasis. SUBJECTS AND METHODS: A 71
      year-old man was diagnosed for unresectable stage IVb pancreatic cancer. This
      patient was given intra-arterial infusion of gemcitabine (GEM) 400 mg/body and
      intravenous infusion GEM 600 mg/body, simultaneously. The day after GEM infusion,
      he was given intra-arterial autologous tumor cell activated T lymphocytes (AuTL).
      RESULTS: Tumor markers, such as CEA and CA19-9, had decreased a little. Primary
      tumor and metastatic liver tumor were reduced, but he died due to intra-abdominal
      dissemination within 5 months after diagnosis of unresectable pancreatic cancer.
      CONCLUSIONS: Reduced primary pancreatic tumor and metastatic liver tumor was
      obtained by locoregional cellular immunochemotherapy. But we could not control
      intra-abdominal dissemination. In conclusion, we suggest that intra-abdominal
      AuLT infusion in combination with intra-arterial AuLT infusion may be advisable
      to patients for unresectable pancreatic carcinoma with intra-abdominal
      dissemination.

PMID- 15553705
TI  - [Distilled water pleurodesis for two breast cancer patients suffering from
      carcinomatous pleurisy].
AB  - Pleural effusion of carcinomatous pleurisy is relatively common and a significant
      problem in recurrent breast cancer patients. It's very important to control it to
      keep a good quality of life for those patients. Two recurrent breast cancer
      patients, suffering from carcinomatous pleurisy and dyspnea due to pleural
      effusion, were treated with distilled water. As they have been treated with many
      kinds of hormonal therapy or chemotherapy for their several distant metastases,
      the performance status of these therapies has not been good. After one or two
      distilled water pleurodesis, pleural effusion was well controlled and dyspnea had
      disappeared. No adverse events, such as high fever and chest pain concerning this
      distilled water therapy were experienced. Taking its efficacy and a rarity of
      adverse events, distilled water plerodesis is a useful treatment for pleural
      effusion of carcinomatous pleurisy.

PMID- 15553706
TI  - [Novel dosage forms with a sustained release of aqueous cis-platinum].
AB  - The authors have been devising novel dosage forms with a sustained release of
      aqueous cis-platinum (CDDP), following the concept of a drug delivery system.
      First, we prepared biodegradable vehicles with clinically available fibrin and
      gelatin materials that were used with the ultraviolet (UV)-cross linking
      technique. Then, each carrier was loaded with CDDP to form new drugs. We
      basically studied degradability of the carrier, a release profile of the CDDP,
      and antineoplastic activities with the system. The new drugs gradually
      disintegrated to dissolve completely within 10-15 days, and 80-90% of the loaded
      CDDP was delivered in the same period. The released CDDP showed antineoplastic
      activities, both in vitro and in vivo, while the CDDP directly reacted with human
      plasma revealed little evidence of anticancer function. The scanning electron
      microscopic studies suggested that the release profile of the CDDP was closely
      related with the degradability of the carrier. We presume that UV-modification
      techniques play important roles in preparation of the new drug carriers. Our
      newly devised CDDP releasing system is promising as novel cancer chemotherapy.

PMID- 15553707
TI  - [Sparassis crispa as biological response modifier].
AB  - Sparassis crispa (SC, Hanabiratake), an edible mushroom which contains beta (1 -
      > 6) branched beta (1 --> 3) glucan in large quantities, was studied on its
      immunomodulative effect. As a result, (1) Tumor size of sarcoma 180-bearing mice
      was smaller than that of control group after 5 weeks by oral administration of
      SC, and thus their survival was prolonged. (2) By administering SC orally, a
      blood IgE level and scratching index of NC/Nga mice, which had been induced
      dermatitis by a continuous application of hapten, were decreased. (3) Human NK
      cell cytotoxicity was enhanced by oral administration of SC without increasing
      the number of NK cell. These results suggest that oral administration of SC
      activates Th1 cell, and inhibits Th2 cell activation, thus promotes a shift in
      the Th1/Th2 balance toward Th1-dominant immunity.

PMID- 15553708
TI  - [The significance of a combination of hepatic artery pump reservoir and new
      immunotherapy for cancer (NITC) in the treatment of colorectal liver metastasis].
AB  - Infusion of anti-cancer agents through a hepatic artery pump reservoir has been
      reported as a relatively useful means of treating multiple liver metastases but
      its mechanism of action remains to be clarified. We thought that immune responses
      might be involved in the mechanism of action of this therapy and attempted to
      test this assumption in patients with colorectal liver metastases. When the
      patients were divided into two groups by survival period (the 24-week or longer
      survival group and the less than 24-week survival group), the 24-week or longer
      survival group had significantly higher Th1 cytokine levels (p<0.001-0.05) and
      significantly lower VEGF levels (p<0.01) than the less than 24-week survival
      group. The survival rate tended to be higher in patients for whom intra-arterial
      infusion therapy was combined with NITC. These results suggest that the combined
      therapy induces some kind of immune reaction closely related to tumor size
      reduction and prolonged patient survival. It seems necessary to compare immune
      activity during intra-arterial infusion therapy alone with activity during intra
      arterial infusion treatment in combination with a new immunotherapy.

PMID- 15553709
TI  - [Analysis of the immuno-activation mechanism of OK-432--phagocytosis, release of
      active components and TLR4 signaling].
AB  - Although we have reported that Toll-like receptor (TLR) 4 is involved in OK-432
      induced anti-cancer immunity, its detailed mechanism remained uncertain. We
      hypothesized that OK-432 may first be captured, dissolved by phagocytes, and then
      active components released from the cells may stimulate TLR4. This hypothesis was
      examined by the current in vitro experiments. We used TS-2 MoAb which recognizes
      OK-PSA, an active component of OK-432. First, we observed that OK-432-induced
      cytokine production by dendritic cells (DCs) and macrophages was significantly
      inhibited by cytochalasin B, a phagocytosis inhibitor. Immunofluorescence
      staining by using TS-2 clearly demonstrated that OK-432 was captured and
      dissolved by these cells. OK-PSA was detected in the supernatants derived from OK
      432-treated DC culture by ELISA with TS-2. The supernatants from OK-432-treated
      DC culture, but not from untreated DC culture, increased NF-kappaB activity in
      TLR4-expressing cells. The increased NF-kappaB activity was inhibited by TS-2.
      These findings elucidated the mechanism mediated by phagocytosis and TLR4
      signaling in the OK-432 action.

PMID- 15553710
TI  - [Anti-cancer effect of an intratumoral injection of dendritic cells expressing
      TLR4 in combination with an active component of OK-432 in TLR4-deficient mice].
AB  - A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432. In
      the in vitro experiments, OK-PSA enhanced expression of MHC class II, CD80 and
      CD86, as well as IL-12 production on dendritic cells (DCs) were derived from wild
      type mice, but not from TLR4-deficient (TLR4-/-) mice. Next we examined the in
      vivo anti-cancer effect of intratumoral administration of syngeneic DCs followed
      by OK-PSA against established tumors in mice. Although OK-PSA augmented anti
      tumor effect of DC administration in tumor-bearing wild-type mice, anti-tumor
      effect of DCs and OK-PSA was not significant in TLR4-/- mice. Interestingly, an
      administration of wild-type mice-derived DCs followed by OK-PSA exhibited a
      marked anti-tumor effect even in TLR4-/- mice. These findings suggest that OK-PSA
      may be a potential adjuvant for local DC therapy, and that DC therapy followed by
      OK-PSA is able to elicit anti-cancer activity even in TLR4-deficient host when
      TLR4 is expressed only in DCs injected intratumorally.

PMID- 15553711
TI  - [Case report on intra-tumor injection therapy of dendritic cells in advanced
      gastric cancer].
AB  - Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted
      attention in recent years from the viewpoint of DC vaccine therapy against
      cancer. However, the existence of an immunosuppressive state in cancer
      individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and
      DC migration to the target organ. It has been reported that injected intra-tumor
      DCs are expected to work phagocytosis of the tumor as a localized effect.
      Consequently CTL induction in the tumor and the regional lymphnodes results in a
      systemic effect. In this study, intra-tumor DC injection therapy was performed by
      means of endoscopic ultrasonography (EUS) in 2 gastric cancer cases. As a result,
      tumor markers and ascites of one case were on the decrease. The results indicate
      this method can be useful in advanced cancer patients.

PMID- 15553712
TI  - [Suppression of peritoneal implantation by NK4 and its mechanisms].
AB  - NK4 suppresses invasion and metastasis of tumor cells by means of dual actions as
      HGF antagonist and angiogenesis inhibitor. Our previous studies showed that NK4
      suppresses the implantation of tumor cells to the peritoneal milky spots (MS) by
      intraperitoneal injection (i.p.) of adenovirus vector expressing NK4 (Ad-NK4) or
      NK4 gene-transfected tumor cells. In the present study, we investigated the
      antitumor mechanisms of NK4 in the suppression of peritoneal implantation. When
      evaluated by a fluorescent microscopy, a prior injection of Ad-NK4 suppressed
      peritoneal implantation immediately after the injection of GFP-expressing tumor
      cells. DNA microarray analyses also demonstrated a reduced expression of some
      adhesion molecules in NK4 gene-transfected tumor cells as compared to neomycin
      gene-trasfected cells (control). In the in vitro adhesion assay, the adhesion to
      some types of the extra cellular matrixs (ECM) was significantly decreased in NK4
      gene-transfected cells as compared to the control. These results suggest that NK4
      may suppress peritoneal implantation by inhibiting adhesion of tumor cells to ECM
      around MS.

PMID- 15553713
TI  - [Study of indoleamine 2,3-dioxygenase expression in patients of esophageal
      squamous cell carcinoma].
AB  - We evaluated the clinical significance of indoleamine 2,3-dioxygenase (IDO) in
      esophageal squamous cell carcinomas. Operative specimens obtained from 30
      patients with esophageal squamous cell carcinomas were investigated by
      semiquantitative RT-PCR with specific primers against IDO. The correlations among
      IDO expression, clinicopathologic factors and prognosis were studied. The
      expression of IDO was observed in 100% of both of the cancer specimens and the
      normal mucosa specimens. The IDO expression of the cancer specimens was higher
      than the normal mucosa specimens. The expression of IDO did not correlate to
      histological classification, growth pattern, lymphatic invasion, venous invasion,
      or lymph nodes metastasis, but correlated to clinicopathological stage, the value
      of immunosuppressive acidic protein (IAP). The group with higher levels of IDO
      expression had a worse survival rate than the IDO expression group with lower
      levels. The serum IDO levels of cancer patients were higher than healthy donors
      measured by semiquantitative RT-PCR and HPLC. It is suggested that the expression
      of IDO in esophageal squamous cell carcinoma patients may play a pivotal role for
      immunosuppression of those patients.

PMID- 15553714
TI  - [Host immunity in colorectal cancer patients treated with low-dose Leucovorin
      plus 5-fluorouracil].
AB  - In colorectal cancer, low-dose Leucovorin plus 5-FU therapy does not induce any
      severe adverse effects, and patients could receive this therapy for many cycles.
      The aim of this study was to investigate the relationship between host immunity
      and this regimen. Seven patients were enrolled in this study. Host immunity was
      investigated before and after chemotherapy. The ratio of Th1/Th2, PHA response,
      serum IAP level and the productions of IL-6, IL-10 and soluble IL-2 receptor did
      not change significantly before and after chemotherapy. Since low-dose Leucovorin
      plus 5-FU therapy might not influence host immunity, patients could receive the
      therapy for a long duration without toxicity.

PMID- 15553715
TI  - [Nonviral gene transfection into human dendritic cells by using biodegradable
      cationized gelatin and plasmid DNA complex].
AB  - Dendritic cells (DC) are potent antigen-presenting cells capable of stimulating T
      cell mediated immunity. Gene transfer of tumor specific antigens or cytokines
      into DC would be a useful strategy for immunotherapeutical purposes. In the
      present study, in vitro transfection of human DCs (hDC) with the complex of
      biodegradable cationized gelatin and an EGFP gene was performed. Flow cytometric
      analyses revealed that approximately 14% of DC was positively expressed for EGFP,
      and the mRNA expression of EGFP gene in transfected hDC was detected by RT-PCR.
      Additionally, when evaluated by allogeneic MLR, the antigen-presenting capacity
      of transfected DC was equal to that of control DC. Cationized gelatin is a
      promising nonviral vector for gene transfer into DC.

PMID- 15553716
TI  - [A case of advanced non-small lung cancer responding to tumor suppressor p53 gene
      therapy].
AB  - The phase I study of the tumor suppressor p53 gene therapy for advanced lung
      cancer was performed. A 57-year-old man with locally advanced squamous cell
      carcinoma at the tracheal bifurcation, clinical stage IIIB, had previously been
      treated by radiotherapy and chemotherapy. Because of the local recurrence, he was
      enrolled to the study. He was treated by a local injection of ADVEXIN once every
      4 weeks for 14 times without marked adverse events, which resulted in tumor
      regression and relief of his symptom for a year. In conclusion, gene therapy with
      ADVEXIN may be an effective treatment for locally advanced non-small lung cancer.

PMID- 15553717
TI  - [A case of metastatic gastrointestinal stromal tumor developing a resistance to
      STI571 (imatinib mesylate)].
AB  - Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the
      gastrointestinal tract characterized by the expression of a receptor that
      activates tyrosine kinase called c-kit. Since malignant GISTs are resistant to
      conventional radiation therapy and chemotherapy, recurrent or malignant GIST has
      an extremely poor prognosis even after surgical resection. The development of a
      tyrosine kinase inhibitor, STI571 (imatinib mesylate, Glivec, Gleevec), which
      inhibits the BCR-ABL, PDGF-R alpha and c-kit receptors, has changed the
      management of unresectable malignant GIST and has improved the survival of
      patients with metastatic disease. We report a patient with GIST and diffused
      peritoneal metastases, whose tumor initially responded to STI571 and eventually
      became resistant. A 45-year-old woman underwent partial jejunostomy on September
      3, 1998, under a diagnosis of submucosal tumor of the jejunum. Pathological
      examination of the primary tumor revealed a strong c-kit expression and GIST was
      diagnosed. The patient underwent an excision of peritoneal recurrences on October
      31, 2000; April 17, 2001; and August 28, 2001. A treatment with STI571 (400
      mg/day) was initiated on October 15, 2001, and she was free from peritoneal
      masses for 8 months after the fourth operation. However, the patient herself
      suspended the STI571 therapy for one month and multiple peritoneal metastases
      developed. Although the treatment with STI571 was restarted at 400 mg/day, the
      peritoneal masses did not respond this time. She died of liver, lung, and
      peritoneal metastases after the seventh cytoreductive operation on February 11,
      2004. Several mechanisms of the resistance to STI571 have been identified.
      Amplification or an overexpression of KIT has been proposed to be involved in the
      resistance development. Several mutations of KIT were also correlated with the
      clinical outcome. Her tumors showed mutations in exons 9 or 11 of KIT, which had
      longer event-free and overall survival times than those tumors that had mutations
      of exons 13 or 17. In this case, an exon 11 mutation of KIT was initially noted.
      After the interruption of the treatment, an additional point mutation arose in
      exon 13 that caused a resistance to STI571. Currently STI571 is the first-line
      therapy for non-resectable GISTs, but a single-agent therapy often leads to tumor
      resistance. It is our hope that we will be able to design an alternative
      treatment to overcome such resistance.

PMID- 15553718
TI  - [Generation of HER2 specific, HLA-A24 restricted CTLs derived from a healthy
      donor].
AB  - Cancer vaccine therapy is one of the latest treatment modalities for advanced
      cancer. In this study, we have newly identified two HER2 peptide epitopes
      restricted by HLA-A24, which are the most common alleles in Japanese. We have
      generated mature DCs from PBMCs in the HLA-A24+ healthy donor. Mature DCs were co
      incubated with HER2 peptide, and then autologous PBMCs were co-incubated with
      antigen-loaded DCs. In this way, we have generated HER2 reactive and HLA-A24
      restricted CTL lines. The CTL's specificity was evaluated with ELISPOT analysis
      and cytotoxic assay. In the two CTL lines, the specificity of TISI loaded with
      HER2/neu peptide used for each CTL induction was recognized, and that specific
      cytotoxicity was also found against cancer cell lines expressing HLA-A24 and
      HER2. In conclusion, we have newly identified two HER2 peptide epitopes
      restricted by HLA-A24 and confirmed that these epitopes will be new targets for
      cancer vaccine therapy.

PMID- 15553719
TI  - [Immunogenic reactivity of CTLs induced by electrofusion cells of human dendritic
      cells and gastric cancer cells].
AB  - In tumor immunotherapy, there were several reports of attempts to induce anti
      tumor immunity by fusion hybrid cells generated with dendritic and tumor cells.
      One of them reported that vaccination of hybrid cells resulted in a remarkable
      reduction of tumor cells in a lab mouse experiment. In our study, fusion cells
      were generated successfully with human matured dendritic and human gastric cancer
      cells by electrofusion technique and employed to induce CTLs. The evaluated
      fusion rate was 47.8% by FACS analysis. We tried to induce CTLs by co culture of
      effector and stimulator cells in the presence of IL-2, IL-7 and IL-12 for 4
      weeks. Although it was not statistically significant in tumor cytotoxic assay,
      effector cells induced by the fusion cells as stimulator cells showed a few
      cytotoxic responses in an immunological tumor specific manner. Our data suggest
      that fusion hybrid cells may facilitate stimulation and expansion of tumor
      specific T cells, but further investigation is required for clinical application
      of fusion cells in adoptive immunotherapy.

PMID- 15553720
TI  - [Histological examination of the effect of hepatic arterial infusion of
      degradable starch microspheres mixed with adriamycin and mitomycin C for liver
      metastases of colorectal cancer--second report].
AB  - We histologically examined the effect of hepatic arterial infusion of degradable
      starch microspheres mixed with adriamycin and mitomycin C (DSM therapy) for liver
      metastases of colorectal cancer. The subjects were 15 liver metastatic lesions
      from 9 patients with colorectal cancer who underwent potentially curative
      hepatectomy after DSM therapy. Ages were ranged from 36 to 71 years old (mean,
      57). The ratio of male to female was 4 to 5. Six patients had synchronous
      lesion(s). A single injection dosage of the DSM therapy was comprised of 300-600
      mg degradable starch microspheres, 30 mg ADM, and 10 mg MMC. Three lesions from
      the two patients who were given a single DSM therapy did not show any
      radiographical changes. In addition, histological examination of these lesions
      demonstrated a grade 1 effect. The radiographical effect of the 12 lesions from
      the 7 patients, who were given the DSM therapy at least three times, showed SD in
      4 lesions, PR in 6 lesions, and PD in two lesions. Histological examination of
      these lesions demonstrated Grade 2 in 4 lesions and Grade 3 in 5 lesions. In
      conclusion, it was histologically confirmed that a repeated DSM therapy could
      cause satisfactory effects beyond expectations by radiographic imaging in
      patients with liver metastases of colorectal cancer.

PMID- 15553721
TI  - [Efficacy of hepatic arterial infusion of adriamycin and mitomycin C mixed with
      degradable starch microspheres for liver metastasis of colorectal cancer-
      correlation with the mRNA expression of DNA topoisomerase-IIalpha and glutathione
      S transferase-pi in primary lesions].
AB  - DNA topoisomerase-IIalpha (topo-IIalpha) is a target enzyme of adriamycin (ADM).
      Glutathione-S-transferase-pi is known to be correlated with the resistance of
      various anticancer drugs including mitomycin C (MMC) and ADM. Expression levels
      of topo-IIalpha and GST-pi mRNA of primary colorectal lesions were semi
      quantitatively determined by the RT-PCR method in 22 patients with colorectal
      cancer, who underwent hepatic arterial infusion of ADM and MMC mixed with
      degradable starch microspheres for synchronous (n=17) or metachronous (n=5) liver
      metastasis. Expression of topo-IIalpha mRNA/beta-actin mRNA was 0.872+/-0.564
      (mean+/-SD) in responders (PR, n=10) and 0.369+/-0.133 in non-responders (SD+PD,
      n=12) (p=0.047). The relative expression of GST-pi was 0.638+/-0.593 in
      responders and 1.014+/-0.682 in non-responders (p=0.22). These results suggest
      that determining the mRNA expression of topo-IIalpha is useful for predicting the
      efficacy for this regimen, whereas determining the mRNA expression of GST-pi is
      not.

PMID- 15553722
TI  - [Evaluation of prophylactic hepatic arterial infusion chemotherapy after curative
      hepatectomy for metastatic colorectal cancer].
AB  - We evaluated the effect of hepatic arterial infusion (HAI) chemotherapy after
      curative resection of liver metastases of colorectal cancer. A total of 161
      patients underwent curative resection of liver metastases. Among them, 50
      patients underwent HAI of 5-FU, and 111 patients had no HAI therapy. The 50%
      disease-free survival time (50% DFS) was 758 days and 342 days in the HAI group
      and the non-HAI group (logrank test, p<0.01), and the 50% overall survival time
      (50% OS) was 978 days versus 730 days (p<0.05), respectively. Among the 71
      patients with multiple resectable metastases (H2 or H3), the HAI group had a
      significantly superior 50% DFS. HAI therapy seems to be an effective form of
      adjuvant chemotherapy after hepatic resection of metastatic colorectal cancer.

PMID- 15553723
TI  - [A case of postoperative pelvic metastasis and multiple liver metastases of the
      rectal cancer successfully treated by arterial infusion therapy with 5
      FU/leucovorin].
AB  - A 55-year-old man underwent a rectal amputation for rectal cancer in 1994. As the
      tumor marker was elevated in 2002, we performed an abdominal CT scan and detected
      local and multiple liver recurrences. We treated the patient with intra-arterial
      infusion of 5-FU/LV via the internal iliac artery and the hepatic artery. The
      chemotherapy was performed on a weekly basis; it consisted of 5-FU (500 mg/body),
      administered for 5 hours to bilateral reservoirs through an infusion pump and l
      leucovorin (400 mg/body), administered intravenously for 2 hours. After 18
      administrations of this regimen during a hospital stay and after a discharge from
      the hospital as an outpatient, the multiple liver metastases that were observed
      have disappeared. Further, the local recurrences showed a partial reduction in
      tumor size with a decrease in perineal pain. Subsequently, the patient did not
      require further doses of morphine. He exhibited no severe side effects except for
      grade 1 nausea, and his QOL was also good. Therefore, local intra-arterial
      infusion chemotherapy with 5-FU/LV appears to have been effective for rectal
      cancer recurrences.

PMID- 15553724
TI  - [A case of unresectable multiple liver metastases from colon cancer successfully
      treated by hepatic arterial infusion chemotherapy and systemic immunotherapy
      (IFNANK) followed by hepatic resection].
AB  - The patient was a 76-year-old man, diagnosed with sigmoid colon cancer with
      unresectable multible liver metastases. After sigmoidectomy with D2 regional
      lymphnode dissection on June 21, 2002 (moderately differentiated adenocarcinoma,
      ss, n(-), H3, P0, M(-), Stage IV), intermittent hepatic arterial infusion
      chemotherapy using 5-FU (1,250 mg/body/3 hr) and CDDP (10 mg/body/30 min) was
      performed weekly for 23 times, and then biweekly for 15 times. The total dosages
      of 5-FU were 47.5 g. During the regional chemotherapy, IFNANK therapy was
      performed biweekly as systemic immunotherapy. As a result, serum levels of tumor
      markers were remarkably decreased, and the metastatic liver tumors had
      disappeared in the CT finding in July 2003. Thereafter, IFNANK therapy was
      continued without the chemotherapy. However, CT and PET detected the recurrent
      liver tumors in December 2003, and the tumors were curatively resected on January
      28, 2004.

PMID- 15553725
TI  - [Intrahepatic arterial chemotherapy with 5-fluorouracil and intramuscular
      interferon-alpha for a patient with diffuse type of hepatocellular carcinoma].
AB  - We report a case of diffuse type advanced hepatocellular carcinoma (HCC), which
      was successfully treated by a combination therapy of interferon-alpha (IFN) and 5
      fluorouracil (5-FU). A 74-year-old man underwent distal gastrectomy 6 years ago
      for gastric cancer. In April 2002, an increased serum alpha-feto-protein (AFP)
      level was noted and a computed tomography (CT) of the abdomen revealed a diffuse
      type of HCC. He was treated with a combination therapy of IFN (5x10(6) units/body
      i.m., days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26) and 5-FU (500 mg/body/day
      i.a., days 1-5, 8-12 continuously). The treatment was repeated every 4 weeks with
      a maximum of five cycles. After 5 cycles, serum AFP levels fell from 665 ng/ml to
      a normal level. CT showed a reduced size of the tumor. He has been well and
      continue to receive IFN (3x10(6) units/body i.m., two times a week) and 5-FU (500
      mg/body/day i.a., once a week) at the outpatient clinic for the last 16 months.

PMID- 15553727
TI  - [CPT-11 hepatic arterial infusion chemotherapy for metastatic liver tumor from
      gastric cancer].
AB  - We have experienced a case of gastric cancer with multiple liver metastases
      resistant to combined treatment of TS-1 and CDDP. After the treatment with TS-1
      and CDDP, abdominal CT demonstrated a progressive growth of metastatic liver
      tumor. Administration of CPT-11 (80 mg/body) by a hepatic arterial infusion
      inhibited the growth of metastatic liver tumor and decreased serum levels of CEA
      and CA19-9 for several months without a significant adverse side effect.

PMID- 15553726
TI  - [A case of radiofrequency ablation therapy for recurrent hepatomas with tumor
      fever--efficacy of hepatic arterial infusion therapy with antibiotics and
      anticancer drugs].
AB  - Efficacy of hepatic arterial infusion therapy (HAI) using antibiotics for hepatic
      abscess has been reported. However, we effectively performed RFA therapy after
      HAI with antibiotics and anticancer drugs for recurrent hepatomas with tumor
      fever. A 67-year-old female of recurrent hepatomas with fever is presented here.
      She was diagnosed with a 6 cm recurrent hepatoma, both in the right and IM lobes.
      Her liver function was child A with hepatitis C. On her CT scan, we found an
      enhanced 60 mm mass at an early phase and it was washed out at a delayed phase.
      Initially, we gave systemic medication of antibiotics, but could not decrease the
      fever. Therefore, we performed HAI with antibiotics and anticancer drugs. The
      patient's temperature went down after 14 days, and we were able to cut down her
      tumor size. After HAI, we were able to completely perform RFA for recurrent
      hepatomas.

PMID- 15553728
TI  - [Cases of postoperative hepatic metastasis from gastric cancer in which hepatic
      arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin was performed
      after TS-1 chemotherapy].
AB  - The prognosis of patients with hepatic metastasis of gastric cancer is poor, and
      standard therapies for patients are not established. Here we present two cases of
      hepatic metastasis from gastric cancer. In both cases, no other organ metastasis
      except the liver was confirmed, in which hepatic arterial infusion chemotherapy
      with 5-FU, adriamycin and cisplatin (FAP) were performed because TS-1
      chemotherapy was not an effective chemotherapy. Case 1: An 80-year-old man had
      distal gastrectomy for type 2 gastric cancer (Stage II) in January 2001. A liver
      S8 metastatic recurrence was discovered in the 18th month post operation. After
      chemotherapy with TS-1 for 5 courses, a hepatic arterial infusion treatment was
      performed for 7 courses. The effect was PR, but the treatment was canceled
      because of a catheter obstruction. The patient is living without recurrence. Case
      2: This case was a 73-year-old man who had distal gastrectomy for type 0 IIc
      gastric cancer (Stage IA) in May 1999. Multiple hepatic metastases recurred in
      the 32nd month post operation. After chemotherapy with TS-1 for 2 courses, a
      hepatic arterial infusion treatment was performed for 10 courses. The effect was
      CR, but a peritoneal recurrence was discovered, and a systemic chemotherapy was
      performed. The patient is living without recrudescence of hepatic metastasis. The
      hepatic arterial infusion chemotherapy with FAP was effective for gastric cancer
      patients with liver metastasis because TS-1 chemotherapy was not an effective
      chemotherapy. It is necessary to consider combined chemotherapy in addition to
      systemic chemotherapy.

PMID- 15553729
TI  - [Long-term survivors with liver metastasis from breast cancer who were received
      intra-arterial chemotherapy].
AB  - Fourteen patients who had liver metastases from breast cancer were treated with
      trans-arterial chemo-embolization (TACE) or intra-arterial chemotherapy via
      percutaneously inserted catheters. The patients were divided into two groups:
      Group A: Long-term survivors who lived longer than three years; and Group B:
      Short-term survivors who died within three years. Then we compared them based on
      the background factors, efficacy of intra-arterial chemotherapy, and so on. There
      was a tendency that Group A had a longer disease-free interval and took more time
      to formulate liver metastases than that of Group B. All of the four patients of
      Group A are alive, and the longest survivor is living six years and four months
      after being diagnosed with liver metastases. In Group B, every patient died from
      liver failure, but one had died from respiratory failure. The objective response
      rate was 38.5%, and four of the five responders were long-term survivors.
      Therefore, it is possible that a good prognosis can be obtained when the hepatic
      arterial infusion chemotherapy effectively controls liver metastases that
      regulate life.

PMID- 15553730
TI  - [The QOL of the patient with advanced pancreatic carcinoma was changed for the
      better with combination therapy consisting of arterial chemotherapy and injection
      of interferon].
AB  - The prognosis of advanced pancreatic carcinoma with multiple liver metastases is
      extremely poor. The current methods of treating pancreatic carcinoma are far from
      satisfactory. The results of systemic and regional chemotherapies for pancreatic
      carcinoma are disappointing. The patient was a 68-year-old male with advanced
      pancreatic carcinoma. After an operation, he received a combination therapy
      consisting of arterial infusion (gemcitabine hydrochloride, GEM, 600 mg) and
      muscle injection of interferon (IFN, 300x10(4) U). A decrease in metastatic tumor
      of the liver was observed. In this report, we describe the case of a patient
      whose effective results were achieved by using a new combination of GEM and IFN.

PMID- 15553731
TI  - [Adjuvant arterial infusion chemotherapy for patients with biliary cancer].
AB  - Although surgery is the only potentially curative treatment for biliary cancer,
      patients frequently develop liver metastasis, local recurrence, and peritoneal
      metastasis after complete resection. Liver metastasis is a common mode of
      progression for biliary cancer, and the prognosis is extremely poor when it
      occurs. Between January 2000 and December 2003, 18 out of 37 patients received
      adjuvant arterial infusion chemotherapy after curative resection of biliary
      cancer. Nine of these 18 patients had bile duct cancer, seven had gallbladder
      cancer, and two had cancer of the papilla of Vater. A catheter was placed using
      Seldinger's technique, with the tip being advanced into the common hepatic artery
      via the femoral artery. Then 1,000 mg/body of 5-FU was administered as a 24-hour
      continuous infusion on days 1-3 and 5-7. Two cycles of this chemotherapy were
      delivered through an angiography catheter without using a reservoir port. This
      treatment caused no severe systemic or abdominal complications. The two groups
      were well balanced with respect to prognostic factors. The 1-year survival rate
      was 76.2% in the adjuvant chemotherapy group versus 52.7% in the non-adjuvant
      chemotherapy group, while the 3-year survival rates were 47.6% and 39.5%,
      respectively (Wilcoxon test, p=0.048). Median overall survival was superior in
      the adjuvant chemotherapy group and the difference was significant. High-dose
      arterial infusion of 5-FU seems to be a safe, tolerable, and effective regimen
      for preventing the postoperative recurrence of biliary cancer.

PMID- 15553732
TI  - [Evaluation of bronchial arterial infusion (BAI) for metastatic lung tumor from
      colorectal cancer].
AB  - Three cases of metastatic lung tumor from colorectal cancer with an ineffectual
      systemic chemotherapy were examined based on the therapeutic effectiveness and
      safety of bronchial infusion (BAI) as a symptomatic therapy. Two out of three
      cases were rectal cancer and the third case being ascending colon cancer. After
      the operations, each of the three cases showed a multiple lung metastases
      recurrence at the primary and metastatic lesions of the lung. The lung metastases
      became large in size and thoracic symptoms (severe cough, chest pain) appeared in
      spite of the systemic chemotherapy of CPT-11, 5-FU and CDDP. A low dosage of BAI
      was administered by using CPT-11 (40 mg/m2) + CDDP (40 mg/m2) as one shot, and
      was repeated (three and six times respectively) for the two cases. When the low
      dosage of BAI was administered, there were light side effects and no
      complications were observed. The average hospital stay was 7.8 days. All three
      patients were stable and showed improvement in the condition of the disease. The
      prognoses from the first BAI were 3, 6, and 9 months in all three cases,
      respectively. BAI using low dosage of anti-cancer agents was effective, as means
      of improving the chest condition and quality of life in patients with metastatic
      lung tumor from colorectal cancer, with an ineffectual systemic chemotherapy.

PMID- 15553734
TI  - [Fundamental studies on locally injected methotrexate bound to activated carbon
      particles (MTX-CH)].
AB  - We developed a new dosage formulation of methotrexate bound to activated carbon
      particles (MTX-CH). In this study, subcutaneous injection of MTX-CH was examined
      for its long-acting effect at the injection sites, anti-tumor effect and acute
      toxicity in mice. MTX-CH- or MTX aqueous solution (MTX-SOL)- was injected locally
      into tumors growing on the back of BALB/c mice at a dosage of 30 mg/kg as
      methotrexate (MTX). (1) The MTX concentration at the injection sites remained
      higher in mice with MTX-CH than that with MTX-SOL. (2) A marked effect on the
      control of tumor growth by MTX-CH was noted after repeated injections throughout
      the observation period. These results suggest that MTX-CH is superior to MTX-SOL
      due to longer-acting effects at the administration site and have a better control
      of tumor growth than MTX aqueous solution (MTX-SOL).

PMID- 15553733
TI  - [Efficacy of intra-peritoneal and intra-venous injection of monoclonal antibody
      A7-NCS conjugates against peritoneal dissemination of the gastric cancer].
AB  - The monoclonal antibody A7 (Mab A7) against human colonic cancer also reacts with
      human gastric cancer at a high rate. We produced a conjugate of neocarzinostatin
      (NCS) with Mab A7 (A7-NCS). The in vitro anticancer effect of A7-NCS on the
      antigen-positive human gastric cancer cell line MKN45 was stronger than that of
      free NCS. Nude mice models of peritoneal dissemination were established by the
      intra-peritoneal inoculation of MKN45. These models were divided into three
      groups. The anticancer effect observed in the group that received the intra
      peritoneal injection of A7-NCS was superior to that observed in the group that
      received the intra-venous injection and the group that received no treatment. In
      conclusion, the intra-peritoneal injection of A7-NCS was a useful treatment
      method for the peritoneal dissemination of gastric cancer.

PMID- 15553735
TI  - [Biodistribution of immune cells in adoptive immunotherapy by using GFP
      transgenic mice].
AB  - All of the cells and tissues from GFP transgenic mice, with the exception of
      erythrocytes and hair, express green fluorescent protein. Additionally,
      lymphokine activated killer cells induced from splenocytes of the mice (GFP-LAK)
      express green fluorescence under the observation by fluorescent microscopy. In
      the present study, we studied the biodistribution of LAK in the two adoptive
      immunotherapy models by injecting GFP-LAK into non-GFP expressing syngeneic mice.
      In peritoneal dissemination model of B16 melanoma cells, intraperitoneally
      injected GFP-LAK accumulated densely on the tumor. On the other hand, in the lung
      metastases model, intravenously injected GFP-LAK stayed scattered around the
      tumor, although they were observed abundantly in the spleen. Our adoptive
      transfer model using GFP transgenic mice is useful for understanding antitumor
      mechanisms induced by adoptively transferred immune cells, without any
      troublesome marking procedures.

PMID- 15553736
TI  - [A case of scirrhous carcinoma of the stomach with malignant pleural and
      peritoneal carcinomatosis responding to the local administration of docetaxel
      (TXT)].
AB  - We report the case of a 34-year-old woman who underwent total gastrectomy for
      scirrhous carcinoma in the stomach (T4, N0, H0, CY1, P1, Stage IV). Despite
      adjuvant chemotherapy with TS-1 and/or CDDP, ascites caused by peritoneal
      carcinomatosis increased four months after gastrectomy. Therefore,
      intraperitoneal administration of docetaxel (TXT) at a dosage of 45 mg/m2 was
      applied. This therapy successfully maintained her good quality of life by
      inhibiting the increase of ascites without any severe adverse side effects for
      more than six months. When the left effusion from pleural carcinomatosis appeared
      nine months after the surgery, the intrathoracic administration of TXT succeeded
      in inhibiting the increase of pleural effusion over five months or more. In this
      case, intraperitoneal and intrapleural administrations of TXT were effective and
      temporarily improved the patient's quality of life without any side effects. We
      thought that the local administration of TXT was a useful treatment without
      severe toxicities for malignant pleural effusion and ascites in scirrhous
      carcinoma of the stomach.

PMID- 15553737
TI  - [A case of gastric cancer with peritoneal dissemination which shows a remarkable
      efficacy by a weekly administration of paclitaxel intraperitoneally].
AB  - We treated a 65-year-old female with gastric cancer who underwent peritoneal
      dissemination after 6 successive weeks of paclitaxel intraperitoneal therapy (90
      mg/body), and obtained a disappearance of ascites and a reduction of the primary
      carcinoma. Operative findings: U ant, type 5, 26x20 mm, por, T2, n1(+), H0, P0,
      CY0, M0, stage II, and grade 2. A weekly paclitaxel intraperitoneal therapy could
      be a useful for both peritoneal dissemination and the primary carcinoma of
      advanced gastric carcinoma.

PMID- 15553738
TI  - [Safety of intraperitoneal chemotherapy with paclitaxel in gastric cancer
      patients with peritoneal dissemination].
AB  - We evaluated the safety of paclitaxel (TXL) via intraperitoneal (i.p.)
      administration in 6 patients with peritoneal dissemination of gastric cancer.
      Four patients were treated with TXL via i.p. administration at a dosage of 80-90
      mg/m2 every 1 to 2 weeks. Grade 4 leukopenia was observed in 1 patient,
      accompanied with massive ascites. Two other patients, who also had malignant
      peritoneal effusion, were treated with TXL via i.p. administration at a dosage of
      60 mg/m2 every 1 to 2 weeks. All toxicities were mild in those two patients. TXL
      via i.p. administration at a dosage of less than 90 mg/m2 has never been reported
      to cause a grade 4 leukopenia. These results suggest that a phase I/II study of
      TXL via i.p. administration should be tried in gastric cancer patients with
      malignant peritoneal effusion.

PMID- 15553739
TI  - [Intraperitoneal chemotherapy against peritoneal carcinomatosis of gastric cancer
      with activated carbon particles adsorbing mitomycin C for four patients].
AB  - Activated carbon particles adsorbing mitomycin C (MMC-CH) was administered to
      four patients with peritoneal carcinomatosis of gastric cancer into their
      abdominal cavities. Tumor markers of CEA, CA19-9, CA125, CA72-4 and STN were
      measured before and after the administration. The waist of each patient was also
      measured. After the administration of MMC-CH, tumor markers of three out of the
      four patients were decreased and a large amount of ascites of all patients had
      disappeared. The appetite of all four patients had increased and complaints such
      as nausea and vomiting had decreased. The mean survival of the four patients was
      291.2 days (123-542 days). Our results suggested that MMC-CH had an anti-tumor
      effect of peritoneal carcinomatosis and improved the QOL of patients with a large
      amount of ascites.

PMID- 15553740
TI  - [A case of recurrent gastric cancer with peritoneal dissemination successfully
      treated with DJ stents against bilateral hydronephrosis and chemotherapy].
AB  - A 69-year-old female patient underwent total gastrectomy with a D2 lymph node
      dissection. Her final findings were of pT2, pN0, sP0, sH0, sM0 and Stage IB.
      After thirty-five months from the operation, peritoneal recurrence with ascites,
      bilateral hydronephrosis and stenosis of colon was found. TS-1 (80 mg/day/body)
      was administered for four weeks followed by a 2-week rest after DJ stents were
      inserted into bilateral ureters. At the end of two courses of TS-1, ascites
      disappeared and the decrease of tumor marker was observed. During the seventh
      course, symptoms such as abdominal fullness and ascites became worse. She
      underwent a weekly administration of paclitaxel (90 mg/body) as a second-line
      chemotherapy. This regimen was continued for three weeks followed by a 1-week
      rest. After four courses of paclitaxel, ascites disappeared and the tumor marker
      was gradually reduced. However, multiple bone metastases were found during the
      eighth course, and she died about two years after the recurrence. The toxic
      events were mucositis (grade 1) in TS-1, and alopecia (grade 2) and leukopenia
      (grade 1) in paclitaxel. No major adverse effects were observed. Although the
      prognosis of recurrent gastric cancer with peritoneal dissemination was extremely
      poor, this case might suggest a possibility that intensive therapies are useful
      in maintaining the quality of life and improving survival.

PMID- 15553741
TI  - [A case of disseminated tumor from cecal cancer with survival for over 5 years
      after twice surgical resection and systemic chemotherapy].
AB  - A 66-year-old man underwent a curative operation for cecal cancer on the 30th of
      November, 1998. Since his CEA level rose in January 2001, computed tomography
      (CT) revealed a tumor in the abdomen. He underwent a resection of this tumor and
      disseminated tumors that were diagnosed during the operation. He received
      systemic chemotherapy (5'-DFUR 600 mg 3x everyday, CPT-11 80 mg/body div every 2
      weeks), but the CEA level rose again in August 2003. He was diagnosed with spleen
      metastasis and underwent splenectomy. The tumor disseminated in the left
      diaphragm was also resected. After that, he received systemic chemotherapy (5-FU
      500 mg/body/week div, levofolinate calcium 250 mg/body/week i.v.) as an
      outpatient. Peritoneal carcinomatosis from colorectal cancer with distant
      metastasis, in general, has no indication for an operation. However, if
      dissemination is located after a sufficient observation period, its resection may
      be recommended.

PMID- 15553742
TI  - [A case of long-term survival after chemo-radiation for postoperative local
      recurrence of rectal cancer].
AB  - The patient was a 64-year-old male who underwent an abdomino-perineal resection
      (D3) for advanced lower rectal carcinoma with a formulated vesicorectal abscess.
      The tumor was a well-differentiated adenocarcinoma, type 2 in the Japanese
      Classification of Colorectal Carcinoma, and was measured 5.5x4.3 cm in size.
      Histologically, the tumor was considered to be stage II (H0, P0, a2, n0 (0/86),
      ly0, v0). He received a postoperative chemotherapy with oral UFT-E (400 mg/day)
      for 1 year. After 2 years from the surgery, the patient developed a perineal
      pain, and pelvic CT scans revealed a 4 cm mass anterior to the sacrum. The CEA
      level was increased to 11 ng/ml. Consequently, a diagnosis of local recurrence
      was made, and radiochemotherapy was commenced. Radiotherapy was given to the
      pelvic region at a total dose of 70 Gy (Given 2 Gy each x 35 fragments).
      Chemotherapy with CDDP and 5-FU was administered via the right internal iliac
      artery followed by administration of 5'-DFUR (600 mg/day). After that regimen, a
      recurrence of the pelvic tumor caused an increase in pain, and the patient
      developed renal failure. He died after 4 years and 10 months from the initial
      detection of recurrence. This report presents a case of local recurrence of
      advanced rectal carcinoma, in which we were able to achieve a long-term survival
      and improvement in QOL by an intensive multidisciplinary therapy.

PMID- 15553743
TI  - [Effectiveness of chemoradiotherapy for three cases of squamous cell anal
      carcinoma].
AB  - We report three patients with squamous cell anal carcinoma who were treated by
      chemoradiotherapy. Case 1: A 62-year-old female with squamous cell anal carcinoma
      invading the vagina underwent a posterior pelvic exenteration. She had paraaortic
      lymph node metastases. She was treated by chemoradiotherapy with 5-FU/CDDP and
      external irradiation (50 Gy) as an adjuvant therapy, and survived for 5 years.
      Case 2: A 74-year-old female with anal squamous cell carcinoma Stage II was
      treated by chemoradiotherapy with tegafur/uracil, external irradiation (30 Gy)
      and interstitial irradiation (24 Gy). She is currently living without any signs
      of recurrence for 3 years and 8 months. Case 3: A 53-year-old female with anal
      squamous cell carcinoma Stage IIIa was treated by chemoradiotherapy using 5'-DFUR
      and external irradiation (66 Gy). She is currently living without any signs of
      recurrence for 1 year and 9 months. The prognosis of anal squamous cell carcinoma
      that received Cur B or C resection was extremely poor with a median survival time
      (MST) of 7 or 6 months. Chemoradiotherapy seems to be effective as the first line
      treatment.

PMID- 15553744
TI  - [Evaluation of intra-arterial infusion chemotherapy associated with radiotherapy
      for two cases of local recurrence of rectal cancer].
AB  - We evaluated the effect of intra-arterial infusion chemotherapy associated with
      radiotherapy for two cases of local recurrence of rectal cancer. We performed an
      intra-arterial infusion chemotherapy (5-FU was injected continuously: 250
      mg/day/body x 28 days, CDDP was injected weekly: 5 mg/day x 5 days) associated
      with radiotherapy (2-3 Gy/day x 20-30 days) for local recurrence of rectal cancer
      with the aim of pain-relief. Both patients markedly tended to feel less pain
      after the radiotherapy. Radiotherapy has been useful for pain-relief of the
      localized bone metastasis. The present intra-arterial infusion chemotherapy
      associated with radiotherapy was a possible local therapy for local recurrence of
      rectal cancer in the pelvis. Although the survival benefit depends on the
      presence of other site of recurrence, this procedure is useful for the
      improvement of QOL by relieving the pain of the patients.

PMID- 15553745
TI  - [Two cases of advanced and recurrent gastric cancer treated with the combination
      of chemotherapy and radiation].
AB  - Recently, new promising anti-tumor agents such as TS-1, taxanes, and CPT-11 have
      been approved for gastric cancer treatment. These agents showed a better response
      and may contribute to a patient's survival and quality of life. However, there
      are cases with advanced and recurrent gastric cancer that are resistive or
      tolerant to these agents. We report two cases in which the patients had suffered
      symptomatic local recurrence during the chemotherapy. Consequently, they had been
      treated with radiotherapy in order to improve their clinical status. We also
      discuss the significance of radiotherapy in gastric cancer.

PMID- 15553746
TI  - [Surgical resection for pancreatic cancer combined with preoperative carbon-ion
      beam irradiation].
AB  - Prognosis of pancreatic cancer is still remarkably poor, even if complete
      resection was performed by enlarged abscission. On the other hand, carbon-ion
      beam therapy is giving good results in some selected carcinoma such as small cell
      lung cancer, prostate cancer, uterus cancer, and soft tissue/bone tumor. In this
      report, we discuss four patients with pancreatic cancer treated by surgical
      pancreatectomy combined with preoperative carbon-ion beam irradiation. All
      patients were irradiated with 48 GyE carbon-iron beam by HIMAC (Heavy Ion Medical
      Accelerator in Chiba) to the pancreatic area including lymph nodes and nerve
      plexus. Severe cholangitis, as the postoperative complication, had occurred in
      one of the patients. However, there was no complication or disorder caused by
      carbon-iron radiation. All four patients are alive now, but two of them developed
      tumor recurrence, one with hepatic metastasis and the other with peritoneal
      dissemination. Surgical treatment for pancreatic cancer combined with
      preoperative carbon-ion irradiation is expected as a promising cure, but it is
      necessary to examine more cases in the future to evaluate the clinical outcome of
      this treatment.

PMID- 15553747
TI  - [The results of liver cryosurgery for synchronized liver metastasis from
      colorectal cancer].
AB  - We examined our results of liver cryosurgery for synchronized liver metastasis
      from colorectal cancer. Twelve patients whose prognosis after the cryosurgery was
      clear were eligible. All of the patients received not only a resection of the
      colorectal primary lesion, but they also received a cryosurgery for liver
      metastases under the same laparotomy. These patients had been treated in this
      manner from 1981 to 1987. Ten of the 12 patients died from recurrent cancer. The
      range in survival time of 12 cases was from 6 months to 117 months, and the
      average survival length was 25.4 months. The examination of the results suggested
      that there were no cryosurgery induced anti-immunological response observed among
      the patients. The survival lengths of the patients with untreated cancer were
      good.

PMID- 15553748
TI  - [The use of radio frequency ablation (RFA) for colorectal liver metastases in one
      patient].
AB  - We studied one case in which the application of RFA was used for colorectal liver
      metastases with cirrhosis. The patient was a 51-year-old male. Sigmoid colon
      cancer and hepatocellular cancer (S5, S6, S8) were diagnosed before surgery. RFA
      was planned, as resection was determined to be impossible, because of reduced
      reserve liver function due to hepatitis B and cirrhosis. Resection of the Sigmoid
      colon was performed. Rapid pathological diagnosis was performed on the liver
      tumor and it was determined to be metastases from the sigmoid colon cancer. RFA
      was performed on the liver tumor with the expectation of local control. After the
      operation, WHF arterial infusion was performed as an outpatient, but the blood
      platelet count decreased and that resulted in impaired liver function making the
      continuation of WHF arterial infusion at a regular pace difficult. After 11
      months from the operation, multiple recurrences appeared and the infusion was
      restarted. Consequently, the tumor size was reduced. Following the infusion,
      however, the liver function became impaired and there was no choice but to
      discontinue the infusion. After one year and 9 months from the operation,
      multiple recurrences appeared in the residual liver and WHF arterial infusion was
      restarted. The tumor size gradually reduced after the infusion and only S3
      currently remains with good local control. Because this example was a case with
      multiple metastases along with a high level of liver function impairment, RFA was
      tested and good local control was achieved. In cases such as these where liver
      resection is not possible, local ablation therapies including RFA are applicable.

PMID- 15553749
TI  - [Bronchoscopic treatment for malignant tracheobronchial stenose].
AB  - We evaluated a bronchoscopic treatment for malignant tracheobronchial stenose in
      28 patients. We performed an ethanol injection treatment in 12 patients,
      bronchoscopic diode laser treatment in 16 patients and airway stent implantation
      in 6 patients by flexible bronchofiberscopy. Each of these treatments is
      comparatively an easy method with no serious adverse reaction. It is suggested
      that these treatments may be effective for tracheobronchial stenose if we select
      patients carefully and combine the methods listed here.

PMID- 15553750
TI  - [Indication of hepatic resection for metastatic liver tumors from gastric
      cancer].
AB  - To clarify the benefit and indication of resection for metastatic liver tumors
      from gastric cancer, we reviewed the therapeutic outcomes at the Niigata
      University Medical Hospital and at a referred institution. From January 1982 to
      April 2004, thirty-nine patients with synchronous and 40 with metachronous liver
      metastases from gastric cancer had been treated. In synchronous cases, forty
      percent of the patients had many metastatic tumors in bilateral hepatic lobes and
      the majority of them had advanced gastric cancer with serosal invasion and widely
      spread of lymphatic metastases. On the other hand, over 70% of metachronous
      patients had unilobar or scattered bilobar metastases and only 20% of them
      accompanied other types of metastases. A survival analysis showed that the
      prognoses of patients undergoing hepatic resection were statistically better than
      other treatments in both synchronous and metachronous cases. And there was no
      evidence for the benefit of palliative gastrectomy. So we conclude that surgical
      treatment for hepatic metastases from gastric cancer is a beneficial option if
      all the lesions including the primary and lymphatic ones can be eradicated in
      limited candidates of synchronous cases and in more candidates of metachronous
      cases, especially unilobar and a few scattered bilobar metastases.

PMID- 15553751
TI  - [A case of disease-free survival of liver and lung metastases of rectal cancer
      resected for a total of five times].
AB  - We report a case of disease-free survival of liver and lung metastases of rectal
      cancer resected for a total of five times. A 54-year-old female with metastatic
      liver and lung tumors of rectal cancer was admitted to our hospital. After a
      radical resection of the original tumor was performed at a previous hospital,
      liver and lung metastases had been confirmed in 1 year and 9 months and in 2
      years and 2 months, respectively, and that both metastases had been resected as
      well. On admission to our hospital, computed tomography (CT) showed a liver
      metastasis of 3-cm in diameter in segment 3 and a lung metastasis of 2-cm in
      diameter in lingular segment. Two surgeries were performed to resect both of
      them. Because of a recurrent liver metastasis observed in segment 4, we performed
      a right hepatic lobectomy and partial duodenectomy 2 years later from the
      surgeries. After the fifth surgery for metastatic lesions, no sign of recurrence
      has been observed in 2 years and 11 months.

PMID- 15553752
TI  - [A case of long-term survival with recurrence leiomyosarcoma of the rectum
      treated by repeated local resections].
AB  - A 47-year-old man was admitted to our hospital for anal pain and diagnosed with
      submucosal tumor by digital examination. Transsacral resection was performed
      because the patient refused a stoma. Leiomyoma with highly malignant potential
      was histologically diagnosed. Surveillance was performed by computed tomography,
      magnetic resonance imaging and digital examination, but a correct diagnosis was
      difficult. Due to local tumor increases in the resected region, trans-anal
      resection was performed 2 years later at the time of local recurrence diagnosis.
      Over the last 10 years, a total of 8 local resections have been performed since
      the first surgery. No distant metastases have been confirmed to the patient
      without a stoma. It appears that a local resection of leimyosarcoma of the rectum
      with a close surveillance was effective.

PMID- 15553753
TI  - [A case report of the local treatment against hepatocellular carcinoma (HCC) in
      consideration of the prospective living donor liver transplantation (LDLT)].
AB  - Various local cancer treatments became possible in the cure of hepatocellular
      carcinoma. Percutaneous ethanol injection (PEIT), a local ablation therapy such
      as microwave and radiofrequency were added to the transcatheter arterial
      chemoembolization (TACE) and hepatectomy. However, it is also a well-known fact
      to repeat hepatic carcinogenesis by the conditions of a background liver whereas
      to originate in the viral hepatitis. In this point of view, liver transplantation
      is one of the ultimate treatments to get rid of the carcinogenic factor. A 54
      year-old man patient diagnosed as HCC strongly hoped for the prospective liver
      transplantation surgery from the beginning. Therefore, we had to treat a liver
      cancer in consideration of the prospective liver transplantation. A local
      ablation therapy and TACE treatment were carried out with being careful not to
      have an influence to the transplantation surgery. Because recurrence was
      repeated, a patient chose a transplantation medical treatment after one year and
      nine months. We reported the process of local treatments against HCC in
      consideration of the prospective liver transplantations.

PMID- 15553754
TI  - [A case report--Efficacy of combination therapy to unresectable advanced gall
      bladder carcinoma--palliative operation, hepatic arterial infusion therapy, and
      radiation therapy].
AB  - A patient of advanced gall bladder carcinoma with liver metastases and direct
      invasions to the duodenum and liver underwent a palliative operation, 3 hepatic
      arterial infusion (HAI) therapies, and radiation therapy at the obstructive
      common biliary duct. (Palliative operation was a partial resection of duodenum
      and transverse colon, HAI therapy with 5-FU (1 g/day) was given as a continuous
      infusion for 6 days, radiation therapy was given 2 Gy/day for 20 times) After the
      combination therapy, the main tumor of gall bladder and hepatic metastases were
      decreased and tumor markers were normalized. (CEA 15.1 ng/ml, CA19-9 93 U/ml to
      CEA 4.4 ng/ml, CA19-9 29 U/ml) Then, an expandable metallic stent (EMS) could be
      inserted to the stenotic common biliary duct after radiation therapy. Although
      para-aotic lymph nodes were existent, systemic chemotherapy (UFT 300 mg/day p.o.,
      MMC 2 mg/week div) has been performed as an outpatient with a good quality of
      life.

PMID- 15553755
TI  - [Utility of dopa decarboxylase as a novel marker for the detection of peritoneal
      micro-metastases of gastric cancer with realtime RT-PCR].
AB  - We have examined the utility of DDC as a novel marker for the detection of
      peritoneal micrometastases of gastric cancer. DDC mRNA in the peritoneal wash
      from 114 gastric cancer patients was quantified for a comparison of
      carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a
      fluorescently labeled probe to predict peritoneal recurrence. The cut-off value
      was set at the upper limit of the quantitative value for non-cancer patients, and
      those above this cut-off value constituted the micrometastasis (MM+) group.
      Thirteen of 15 cases with peritoneal dissemination were MM+DDC (87% sensitivity),
      and one of 48 t1 cases was MM+ (98% specificity). DDC levels in peritoneal washes
      from patients with synchronous peritoneal metastases were more than 50 times
      higher than in those from patients without metastasis (p<0.01). For 15 cases of
      peritoneal dissemination (seven cases were cytologically positive), DDC was
      positive in 13 cases (87% sensitivity), but CEA failed to detect micrometastases
      in four cases (73% sensitivity), indicating that DDC is in some cases superior to
      CEA for the detection of peritoneal micrometastases of gastric cancer in terms of
      sensitivity as well as specificity, especially for poorly differentiated
      adenocarcinomas. Combination of CEA and DDC improved the accuracy of diagnosis up
      to 93%. These results suggest that DDC is potentially a novel marker for
      peritoneal dissemination of gastric cancer and that quantitative RT-PCR of DDC is
      reliable and efficient for the selection of patients for adjuvant intraperitoneal
      chemotherapy to prevent peritoneal recurrence.

PMID- 15553756
TI  - [Over expression of Reg IV in peritoneal dissemination of gastric cancer].
AB  - We previously performed a global analysis of the gene expression of gastric
      cancer cell lines established from peritoneal dissemination (SNU-5, SNU-16, SNU
      719, KATO-III and GT3TKB) with the cDNA microarray method to identify the novel
      markers for the detection of micro-metastasis in peritoneal cavity. One of the up
      regulated genes is Reg IV, which is a member of the Reg gene family belonging to
      calcium dependent lectin (C-type lectin) gene superfamily. We have examined Reg
      IV potential as a novel marker for the detection of peritoneal micro-metastases
      of gastric cancer. Reg IV expression was examined in five gastric cancer cell
      lines established from peritoneal dissemination and compared with myeloid
      leukemia cell (HL60), methothelial cell lines Met5A and the other gastric cell
      line established from primary tumor (SNU-1) by quantitative real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR). Reg IV was highly overexpressed
      in 4 gastric cancer cell lines established from peritoneal dissemination, but
      weakly expressed in other cell lines. According to Reg IV mRNA expression levels
      in surgically resected specimens, the quantity of Reg IV correlated with wall
      penetration. Furthermore, Reg IV mRNA expression level in the peritoneal wash
      from 35 gastric cancer patients was also prone to correlation with wall
      penetration. These results suggest that Reg IV may be involved in peritoneal
      dissemination of gastric cancers and Reg IV may be a potential novel marker for
      peritoneal dissemination of gastric cancers.

PMID- 15553757
TI  - [Nobel genes improve accuracy in detection of peritoneal micro-metastasis of
      gastric cancer to decide indication for chemotherapy].
AB  - Peritoneal metastasis is the most frequent form of recurrence for advanced
      gastric cancer. We previously performed a global analysis of the gene expression
      of gastric cancer cell lines established from peritoneal metastasis with cDNA
      microarray. One of the up-regulated genes is L-3 phosphoserine phosphatase (L3
      PP). We have examined its potential as a novel marker for the detection of
      peritoneal micrometastasis of gastric cancer. L3-PP mRNA in peritoneal wash in 93
      gastric cancer patients was quantified for comparison of carcinoembryonic antigen
      (CEA) mRNA by means of real-time RT-PCR to predict peritoneal recurrence. The
      quantity of L3-PP and CEA correlated with wall penetration. Eleven out of 18
      cases with peritoneal dissemination were L3-PP+ (61% sensitivity). For three out
      of 18 cases of peritoneal dissemination, only L3-PP could detect micrometastasis
      of gastric cancer. Consequently, free cancer cells that cannot be detected by CEA
      mRNA could be detected using L3-PP mRNA. Although CEA alone was not sufficient,
      L3-PP and CEA in combination can attain a higher accuracy of detection.

PMID- 15553758
TI  - [A case of Vp3 hepatocellular carcinoma with a good QOL after multidisciplinary
      treatments].
AB  - A 74-year-old male was examined with abdominal CT scan because of general
      fatigue. Abdominal CT scan indicated enhanced tumors, 9x8 cm in size in
      subsegment 6/7 and 5 mm in size in subsegment 3. Tumor thrombus was observed in
      the right portal branch to the main portal vein. We diagnosed the patient with
      Vp3 hepatocellular carcinoma. A right hepatectomy with extraction of portal
      venous thrombus was performed. Unresectable tumor was treated with one shot
      arterial infusion (epi-ADM 40 mg) and TAE 3 times at an interval of three months.
      The side effect was only a fever and the QOL was good under the treatment. But a
      tumor in S1 had developed, and the patient died at about 12 months after the
      operation.

PMID- 15553759
TI  - [Non-surgical treatment of hepatocellular carcinoma with tumor thrombus in the
      right atrium].
AB  - A 65-year-old Japanese man who had been suffering from severe and progressive
      dyspnea for more than 2 months underwent an extended right hepatectomy for
      hepatocellular carcinoma (HCC) in August 2001. Radiological examination,
      performed in August 2003, revealed the mass in the left lobe of the liver
      extended into the left hepatic vein, the inferior vena cava and the right atrium.
      Those clinical manifestations were supposedly attributed to HCC tumor thrombus in
      the right atrium. The decision to carry out the palliative operation for the
      tumor thrombus was not made because of poor prognosis in light of hemodynamic
      compromise indicating a reasonable liver function. A sequential course of
      treatments for the tumor thrombus was performed including transcatheter
      chemotherapy, transarterial chemoembolization and radiation therapy. Although a
      radiological response rate was 27% in diameter of the tumor thrombus, the
      clinical manifestations, such as dyspnea or edema, completely disappeared during
      the treatment. No surgical standard or interventional regimen for HCC tumor
      thrombus in the right atrium has been established. However, we here demonstrated
      the possibility for the treatment of the tumor thrombus with intensive
      combination therapies.

PMID- 15553760
TI  - [Multidisciplinary treatment for advanced hepatocellular carcinoma with portal
      vein tumor thrombosis and adrenal/lung metastases].
AB  - The patient was a 73-year-old male who was identified with an increase of serum
      PIVKA-II during a treatment for chronic hepatitis B. Hepatocellular carcinoma
      (HCC) of 60 mm in diameter with satellite nodules was diagnosed in segment 8 of
      the liver. In addition, portal vein tumor thrombosis (PVTT) of the right branch
      (Vp3) and metastases to bilateral lung and right adrenal gland were recognized.
      He received serial treatments with transcatheter arterial chemoembolization
      (TACE), radiation therapy and hepatic arterial chemotherapy with reservoir for
      primary liver tumor and PVTT. Soon after the treatments, PVTT was reduced in size
      and the serum level of PIVKA-II was decreased to 57 mAU/ml. After three months,
      the level of PIVKA-II had increased again and the size of the right adrenal
      metastasis grew to 50 mm in diameter. He received TACE to the right adrenal
      metastasis and percutaneous transhepatic portal chemoembolization to prevent
      further growth of PVTT. In spite of several treatments, the therapeutic effect
      was insufficient. Therefore, we performed right adrenalectomy and radio-frequency
      ablation of HCC in the liver S8. After the surgery, he received two times of TACE
      and the viable tumor had disappeared on CT and MRI. Prognosis of HCC with PVTT
      and distant metastasis is very poor. The two-year survival rate is less than 10%.
      However, it is possible to improve the prognosis of advanced HCC by
      multidisciplinary treatment with surgical intervention, local chemotherapy and
      radiation therapy.

PMID- 15553761
TI  - [Evaluation of multimodality therapy for synchronous liver metastases of gastric
      cancer].
AB  - We evaluated the significance of multimodality therapy for cases of liver
      metastases of gastric cancer. Accumulated survival rate and median survival time
      were analyzed for twenty cases of such gastric cancer. Survival rates of H1+H2
      group and hepatic resection (HR) group were higher than that of H3 group and non
      HR group. MST of HR group and hepatic arterial infusion (HAI) group were longer
      than that of non-HR group and non-HAI group. Survival rate of HAI group was
      higher than that of non-HAI group among eleven cases of HR group. On the other
      hand, survival rate of HR group was higher than that of non-HR group among eleven
      cases of HAI group. These results suggested that HAI chemotherapy after hepatic
      resection for gastric cancer patients with synchronous liver metastasis would
      improve prognosis.

PMID- 15553762
TI  - [A case of local advanced breast cancer with multiple lung metastases
      successfully treated with multimodal therapy].
AB  - We report a case of local advanced breast cancer with multiple lung metastases
      (T4bN2M1) achieving a significant improvement of QOL by multimodal therapy with
      chemotherapy, antibody therapy, radiation therapy and surgery. The patient was a
      47-year-old woman with mental deterioration who had an ulcerative breast cancer
      with multiple lung metastases. Breast biopsy led to a diagnosis of an invasive
      ductal carcinoma positive for erbB2 protein expression. She received 6 cycles of
      tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although metastases in
      the lung disappeared after chemotherapy, the response of breast ulceration was
      less satisfactory. Simple mastectomy followed by radiation therapy (50 Gy) to the
      axilla was performed as a palliative treatment. No signs of recurrence were
      observed for more than 14 months of treatment by trastuzumab. Multimodal therapy
      can improve patient QOL and the clinical outcomes in Stage IV local advanced
      breast cancer.

PMID- 15553763
TI  - [A case of lymph node metastasis after 7 years from Hartmann's operation for
      stage IV sigmoid colon carcinoma].
AB  - The case was a 49-year-old woman. In 1995, she underwent Hartmann's operation for
      sigmoid colon carcinoma. Histological stage was IV [se, n4(+), P0, H0, M(-)].
      Adjuvant chemotherapy was performed by MMC and 5'-DFUR. After 7 years from the
      surgery, she had a lumbar pain. CT examination revealed a retroperitoneal tumor
      like shadow and Para-aortic lymph nodes were swelling. In 2002, she underwent
      probe laparotomy. There were massive lymph nodes metastasis, and tumor resection
      was impossible. Following several systemic chemotherapies such as UFT/CPT-11 and
      TS-1, the tumor progressed and liver metastasis appeared. After 9 years from the
      first operation, she is still able to eat and her performance status is 1.

PMID- 15553764
TI  - [A case of unresectable pancreatic cancer showing tumor dormancy treated with
      gemcitabine].
AB  - A 67-year-old woman visited our hospital with a chief complaint of epigastralgia.
      The patient was diagnosed as having unresectable pancreatic cancer because
      abdominal CT and angiography revealed a tumor that had invaded a common bile
      duct, portal vein and superior mesenteric vein. A palliative operation was
      performed because of obstructive jaundice. Peritoneal dissemination was observed
      and confirmed pathologically. The patient was treated with gemcitabine after the
      palliative operation. A gemcitabine 30 min i.v. infusion at a starting dose of
      1,000 mg/m2 was administered once a week for 3 weeks with a 1-week rest. The
      patient experienced grade 2 leukocytopenia, so the dose of gemcitabine was
      reduced to continue the chemotherapy. The patient continued to undergo the
      palliative chemotherapy without severe adverse effects. As a result, the patient
      was in tumor dormancy for 15 months. It is important for the patient to induce an
      acceptable level of toxicity in clinical practice and to continue the
      chemotherapy.

PMID- 15553765
TI  - [A case of gastric endocrine cell carcinoma with neck lymph node metastasis
      resected after neoadjuvant chemotherapy].
AB  - A relatively rare case of gastric endocrine cell carcinoma was reported. The
      prognosis of this disease appears to be very poor due to its rapid rate of growth
      and invasiveness. A 75-year-old woman underwent a gastric endoscopy because the
      patient complained of an appetite loss. A gross Borrmann 3 type lesion in the
      greater curvature of the fornix was found. Biopsy specimens showed endocrine cell
      carcinoma. Abdominal CT examination revealed metastases in left neck and
      paraaortic lymph nodes. The serum sample showed an elevation of NSE level to be
      53. A combination chemotherapy was performed using cisplatin and etoposide, which
      resulted in remarkable reduction of the main tumor two months later. The total
      gastrectomy associated with D2 lymph node dissection was performed. However,
      abdominal tumor was observed again in a month and it progressed rapidly. No clear
      response to the chemotherapies with cisplatin/etoposide or paclitaxel was found.
      The patient died 5 months after the operation.

PMID- 15553766
TI  - [A case of long-term survivor with multiple pulmonary metastases of HCC after
      hepatic resection].
AB  - A 52-year-old male was admitted to our hospital with huge hepatoma of the right
      lobe. He underwent a right lobectomy of the liver in July 1999. After five months
      from the surgery, multiple recurrences in the liver and lung were revealed with
      Computed tomography (CT). TAE was performed for intrahepatic recurrence and a
      combination therapy, consisting of UFT and interferon-alpha, was started for
      pulmonary metastasis. Then 5-FU/CDDP/interferon-alpha therapy was given in 2001
      and TS-1/interferon-beta therapy was given thereafter in 2002. Consequently, the
      patient survived for 31 months with no disturbance in quality of life. No
      intrahepatic recurrence was also detected during the survival period. It was
      suggested that a good prognosis may be expected, even in the HCC case with
      distant metastasis after hepatic resection, if the primary cite was curatively
      treated.

PMID- 15553767
TI  - [Application of metallic stents for both inferior vena cava and biliary
      obstruction by lymph node involvement in a patient with recurrent hepatocellular
      carcinoma].
AB  - The authors experienced a case with obstruction of the inferior vena cava (IVC)
      and the common bile duct due to a recurrent hepatocellular carcinoma. In order to
      improve severe edema of the lower extremities and obstructive jaundice, IVC
      metallic stent as well as biliary stent were applied. A Luminexx stent of 8 cm in
      length was placed in the bile duct via subcutaneous route after biliary drainage.
      A spiral zigzag stent of 8 cm in length was also inserted into the IVC through
      the femoral vein following balloon dilatation of the obstructed portion.
      Subsequently, jaundice and edema were dramatically improved in a short period of
      time, which resulted in patient discharge from the hospital. Although the patient
      died of the cancer in 2 months, the quality of life was well maintained until
      death.

PMID- 15553768
TI  - [Variability of the hard dorsal idiosomal tegument pattern and other phenotypic
      characters as a manifestation of microevolution in Dermacentor marginatus (Acari:
      Ixodidae)].
AB  - The pattern of male conscutum and female scutum in Dermacentor marginatus has
      been examined in 6 points of the East-European and Asian parts of its range (Fig.
      1). A high rate of modification variability of the pattern has been recovered in
      each geographical sample. It is shown that populations differ reliably from each
      other by the length of the dark patches on the marginal flank of the conscutum
      (nkappabeta, npkappabeta, 3kappabeta); some samples also differ by the number of
      these patches, complexes of other patches of the scutum and conscutum, and as
      well (visually) by the color density of light fields and contrast between them
      and the dark background on the conscutum and scutum (Table 1, 2). Besides, the
      samples differ reliably at each stage by the complexes of morphometric characters
      (Table 3, 4). The sample from the Peter the First Ridge is most deviate from
      others by the color contrast and complex of patches both in males and females.
      However, by the patches of marginal flank and morphometric characters of both
      sexes and perimaginal stages this sample differ less from others. The sample from
      the Stavropol plateau having most variable pattern (Fig. 3, 1-9, 4, 1-3) is
      characterized by the greater number of statistically reliable differences by the
      patches (nkappabeta, npkappabeta, 3kappabeta) and morphometric characters of all
      stages of the ontogenesis from all other samples. Other geographical samples have
      intermedial position in regard to degree of differences from each other. The
      samples examined are considered as morphotypes; degree of differences between
      morphotypes is unequal. The phenotypic differences have mosaic dispersion among
      ontogenetic stages and do not show a coherent direction in comparing the
      morphotypes. Differential characters of the morphotypes and related tick species
      belong to different structures or their different parameters. Possible ways of
      morphotype's origin and geochronological characteristics of morphotypes are
      discussed.

PMID- 15553769
TI  - [Variability in Leptotrombidium europaeum and two new related chigger mite
      species (Acari: Trombiculidae) from Caucasus].
AB  - Two new chigger mite species closely related to Leptotrombidium europaeum (Daniel
      et Brelih, 1959) are described from small mammals collected in Caucasus and
      Transcaucasia. L. alanicum sp. n. differs from L. europaeum in having shorter
      legs (TaIII = 61-81, Ip = 734-927 versus 72-90, and 855-1017), shorter scutal and
      idiosomal setae (D(min) = = 30-45, D(max) = 48-67, H = 59, PL = 58 versus 40-52,
      54-69, 64, 63), slightly smaller scutum (AP = 25, SD = 47, PW = 89 versus 28, 50,
      91), and more numerous idiosomal setae (87 versus 81). L. montanum sp. n. differs
      from L. europaeum in having more numerous idiosomal setae (102 versus 81), longer
      scutal and idiosomal setae (AM = 61, AL = 44, H = 68, D(max) = 66 versus 56, 41,
      64, 62), thicker legs (TaW = 19 versus 18), and broader scutum (PW = 95 versus
      91). Exact identification of both new species is possible only using
      classification functions constructed by means of discriminant analysis. These
      three Leptotrombidium species expose sympatric distribution in Daghestan (Eastern
      Caucasus). L. alanicum and L. montanum also occurred together in Krasnodar
      Territory (Western Caucasus). Each of these species includes a number of local
      geographical forms precisely distinguished from each other. Morphometric
      differences between L. alanicum and L. montanum agree with eco-geographical rules
      being previously found in chigger mites from other genera. However, differences
      between local forms of these species show other tendencies directed
      controversially in part. Therefore it is probable that interspecific differences
      in this case correspond to the variability which took place in the process of
      speciation.

PMID- 15553770
TI  - [Molecular genetic methods for the identification of the urban mosquito Culex
      pipiens pipiens F. molestus (Diptera, Culicidae)].
AB  - Molecular genetic methods for the identification of two ecotypes, or forms
      (pipiens and molestus) of the Culex pipiens pipiens mosquitoes, which are known
      as active bloodsuckers and vectors of various agents of diseases, are proposed.
      For the DNA analysis, two populations of the urban mosquitoes (the molestus
      ecotype) from St. Petersburg and Moscow and two populations from the overground
      reservoirs in the Leningrad Province and neighboring areas of Moscow (the pipiens
      ecotype) have been studied. These ecotypes differ by six transitions among 247
      nucleotide sequences of 3' part of the cytochrome oxidase subunit I (COI) gene of
      mitochondrial DNA (mtDNA), by the mtDNA fragments resulted from the restriction
      analysis and by the lengths of second internal transcribed spacer (ITS2)
      sequences in the ribosomal DNA.

PMID- 15553771
TI  - [Seasonal dynamics of the component community structure of parasites of the
      minnow Phoxinus phoxinus (L.)].
AB  - The material represented by 75 specimens of minnow of the age 2-2(+) was
      collected according to the standard technique in the Chovju River (tributary of
      the Vychegda River, a region of the settlement Nizniy Chov, district of Syktyvkar
      town) during the period June-September 2000. The quantitative estimation of the
      structure of the component parasite communities was performed by calculating
      errors of the equation of regression for each species group separately, with
      subsequent summarizing of means of errors by all parasite groups comprising the
      community (Dorovskikh, 2001 6; 2002 B). In order to have a possibility to get
      data complementing each other, the calculation of variety indexes and other
      indexes have been made for metazoan parasites only and for the whole community,
      including the protozoan parasites. In both cases, i.e. considering only metazoan
      parasites and the whole composition of parasite species, three states of the
      component parasite community have been recognised: the formed community (June),
      the community in destroying (July and August), the community in the process of
      formation (September). In the course of working on the total species composition
      we recorded the beginning of community destroying on 30th of June, and the
      beginning of community formation in August. Considering only the metazoan
      parasites, the community is defined (after: Pugachev, 1999) as the mature
      (balanced) one in June, while in July, August and September, it was unmature (off
      balance) by its characteristics. Regarding the protozoan parasites, the community
      in June, August and September was characterized as the mature one based on
      indices of parasite biomass, and as unripe one based on the number of parasite
      individuals; however in July, both groups of indices allowed to refer it to the
      unripe state. However, these unripe states are essentially different. In July, it
      is the result of dieing out the parasites of the past generation; in August and
      September, it is the result of the appearances of new generations. Therefore we
      recognise three states of parasite community named above. Considering the whole
      species composition of parasites we noted the greater difference of index values
      based on the parasite specimen numbers and their conventional biomass, that was
      in the case of the metazoan parasites only. It is particularly noticeable in the
      middle of the June, in the period of the formed community. This fact, together
      with high errors of the equations of regression and the presence of the high
      number of Apiosoma, points to the disturbance in the structure of component
      parasite community in the minnow from the Chovju River. This is easily
      explicable, because the Chovju River is the polluted reservoir, and pollution
      comes from agricultural fields, Verhny-Chov settlement, pigsties and cow-sheds.
      The pollution is a seasonal factor here. The most powerful pollution was noted at
      May-June, and then it decreased along the beginning of rains in the end of
      August; in September it increased again. It is important to point out that the
      monitoring of the metazoan parasites only allows to reveal the general dynamics
      of the community during the period of observation, but does not allow to catch
      the beginning of its destroying and developing and to notice possible
      disturbances in the community structure caused by pollution of reservoirs,
      particularly, if this pollution is a seasonal factor as in the Chovju River.
      Three named states of the component community of the fish parasites take place in
      other periods of year than this observed in the intestional parasite communities
      of fish helminths of the temperate climate zone. The developing of parasite
      communities of the intestinal helminths of the Anguilla anguilla in England
      (Kennedy, 1997) and of Leuciscus idus from the Rybinsk reservoir (Zhohov, 2003)
      starts in the beginning of summer. In May, their species diversity is minimal and
      in August is maximal. In conditions of the middle stream of the Vychegda River,
      the species diversity of parasite community associated with the minnow is maximal
      in June and minimal in August, when it only begins developing.

PMID- 15553772
TI  - [Phylogenetic analyses of the family Tetraonchidae (Platyhelminthes: Monogenea)].
AB  - A phylogenetic reconstruction of the monogenean family Tetraonchidae was carried
      out by methods of parsimony-based cladistics. The analysis included 20 species of
      tetraonchids and two out-groups (Sundanonchus tomanorum and Dactylogyrus
      amphibothrium) and was based on 34 morphofunctional characters. Software PAUP 4.0
      and Winclada were used for the phylogenetic reconstructions. Obtained results
      allow proposing a preliminary phylogenetic hypothesis of the family Tetraonchidae
      along with the discussion of host-parasite association. According to the current
      taxonomic view, the family Tetraonchidae included two genera. Cladistic analysis
      showed a monophyly of the family and the genus Tetraonchus Diesing, 1858. Two
      representative of the former genus, Tetraoncus monenteron and T. borealis,
      parasitize the pikes (Esocoformes: Esocidae) and the grayling (Salmonidae:
      Thymallinae) respectively. The genus Salmonchus Spassky et Roytman, 1958 has a
      complicated structure and its intrageneric relationships were not completely
      resolved; in general, the analysis allows to recognise several species groups:
      Salmonchus oncorhynchi--the parasite of the Oncorhynchus masou smolt living
      during the first year of life in fresh water; four species (S. variabilis, S.
      gussevi, S. grumosus, S. alaskensis) inhabiting specifically the whitefishes
      (Salmonidae: Coregoninae); all reminder of Salmonchus species occurring on the
      salmons (Salmonidae: Salmoninae). The bootstrap test gives a support only for the
      following clades: family Tetraonchidae (75%), genus Tetraonchus (88%); a group of
      Salmonchus species associated with the whitefishes (93%) and grouping of four
      species (S. huhonis, S. pseudolenoki, S. skrjabini and S. lenoki) from the lenoks
      (Brachymystax) and taimens (Hucho) (61%).

PMID- 15553773
TI  - [Polymorphism and structure of the population of Proteocephalus longicollis
      Zeder, 1800 (Cestoda: Proteocephalidae) in the vendace Coregonus albula L].
AB  - Polymorphism and phenotypic diversity of a hostal ecoform of Proteocephalus
      longicollis from its typical host, the vendace, Coregonus albula L., were
      studied. A complex phenotypic structure of the parasite population and presence
      of morphologically different groupings were revealed. We distinguished four
      groupings based on the external characters and three groupings based on the feed
      and reproduction features; among latter groupings one has very specific
      variations of features. We conclude that P. longicollis has high intraspecific
      and intrapopulation heterogeneity, and the host plays a stabilising role in the
      parasite species formation.

PMID- 15553774
TI  - [The population dynamics of the water shrew Neomys fodiens (Mammalia, Soricidae)
      and its helminthes fauna in the Northern Baraba].
AB  - The water shrew population was studied in Ust-Urgulca (Novosibirsk Province) in
      1978-1990; abundance, sex and age structure, reproduction rate of this animal and
      its helminth fauna were examined. It was found that the abiotic factors (in
      particular the water level of habitat areas) influenced on the water shrew
      populations. The number of water shrews increased when the high water level
      increased. In these conditions, the population of the water shrew rejuvenated and
      the numbers of females increased with some increasing their fertility. In the
      helminthes fauna associated with the water shrew, predominated the parasite
      species developing in water invertebrates or ones living near water basins. When
      water habitats dried out, the number of water shrews decreased and individuals
      retained only in some areas and the population became old.

PMID- 15553775
TI  - [Microsporidia of the genus Parahtelohania (Microspora: Amblyosporidae) from
      blood-sucking mosquitoes of the genus Anopeles (Diptera: Culicidae) from the
      South of the West Siberia].
AB  - Five new microsporidian species of the genus Parathelohania have been found in
      the fat body of blood-sucking mosquitoes collected in various water basins in the
      South of West Siberia: Parathelohania divulgata sp. n., P. formosa sp. n., P.
      sibirika sp. n., P. teguldeti sp. n., and P. tomski sp. n. Processes of merogony,
      sporogony, and ultrastructure of spores was were investigated by means light and
      electronic microscopy.

PMID- 15553776
TI  - [The description of Wallaceina vicina sp. n. (Kinetoplastida: Trypanosomatidae),
      from the water strider Gerris rufoscutellatus Latreille, 1807 (Hemiptera:
      Gerridae)].
AB  - A new homoxenos trypanosomatidae, Wallaceina vicina sp. n., is described from the
      digestion tract of the water strider Gerris rufoscutellatus. The laboratory
      culture of W. vicina has been obtained. Flagelated have been studied with TEM.

PMID- 15553777
TI  - [Crepidulospora--nomen novum for the junior generic homonym (preoccupied generic
      name) Crepidula].
AB  - Crepidulospora nom. nov. is a replacement generic name for the genus Crepidula
      Simakova, Pankova et Issi, 2003 based on the type species Crepidula beklemishevi
      Simakova, Pankova et Issi, 2003 (Microsporida) from Anopheles beklemishevi. The
      name proposed by Simakova et al., 2003 is a preoccupied name, because it was
      already used for the gastropode Crepidula Lamarque 1899 (Echinospirida,
      Calibraeidae), a parasite of Mytilus. A valid name of the type species of the
      genus is now Crepidulospora beklemishevi (Simakova, Pankova, Issi, 2003) comb. n.
      Crepidulospora Simakova, Pankova et Issi nom. non. Type species: Crepidula
      beklemishevi Simakova, Pankova, Issi, 2003. Diagnosis. Sporogony is
      octosporoblastic. Sporogonal stages are in direct contact with host cell
      cytoplasm. 8 uninucleate spores, 4.2 x 2.2 mkm, are sandals-like. Polar tube is
      anisofilar, with 6-7 coils (2 + 4-5). Polaroplast is three-partite, with broad
      vesicular, vesicular and lamellar compartments. Microsporidia ilnfects larval
      adipose tissues. Type host: Anopheles beklemishevi (Diptera, Culicidae).

PMID- 15553778
TI  - [Prospects for practical application of substrate-binding modules of glycosyl
      hydrolases (A review)].
AB  - The properties of substrate-binding modules of glycosyl hydrolases have been
      reviewed. Variation of the properties of these modules makes them promising as
      components of chimeric proteins, which is a rapidly developing field of
      biotechnology. Examples of applying substrate-binding modules of glycosyl
      hydrolases to immobilization of proteins and whole cells on polysaccharides and
      purification of proteins are described. Promising methods for (1) detecting
      various compounds using hybrids of substrate-binding modules with antibodies and
      (2) locating polysaccharides in live tissues are reviewed as well.

PMID- 15553779
TI  - [Precipitated, coprecipitated, and carbon-mineral sorbents for isolation of
      extracellular catalase from Penicillium piceum F-648].
AB  - The abilities of various sorbents to adsorb catalase (CAT; EC 1.11.1.6) from
      filtered culture liquid (FCL) of the fungus Penicillium piceum F-648 were
      compared. Potassium phosphate, hydroxyapatite (HAP), and coprecipitated sorbents
      containing calcium phosphate and magnesium hydroxide adsorbed extracellular CAT
      more efficiently than aluminum oxide, aluminum phosphate, or quartz sand. The
      enzyme was isolated from FCL of Penicillium piceum with the use of HAP and a
      binary coprecipitated sorbent, Ca3(PO4)2 + Mg(OH)2, 1:1 (CM). The CAT(CM) sample
      contained the least amount of protein admixture. Its spectra had absorption
      maximums at 279.6, 406.8 (Soret band), 540, 585, 636, and 703 nm and negative
      molar ellipticity minimums at 207 and 210-214 nm. The kinetic indices of the
      samples (KM, Vmax:KM, and specific activity) were intricately dependent on
      protein concentration in the reaction mixture. In dilute solutions, the KM and
      specific activities of CAT(CM) and CAT(HAP) equaled 667 and 137 mM; 300.9 x 10(4)
      and 30.0 x 10(4) U/mg protein, respectively. The effective velocity constants of
      inactivation of CAT(HAP), CAT(CM), and FCL in the reaction of H2O2 decomposition
      increased dramatically after dilution of samples. In the infinitely dilute
      solution, they were 4.30 x 10(-2), 6.46 x 10(-2), and 1.12 x 10(-2),
      respectively.

PMID- 15553780
TI  - [Effect of pasteurization on the activity of proteinases in salmon roe].
AB  - We studied the dependence of activity and stability of proteolytic enzymes in
      salmon roe on pH and temperature. The activity of proteolytic enzymes in roe was
      primarily determined by proteinases. These enzymes were active at acid pH and had
      an optimum of 3.6. A study of subclasses of proteolytic enzymes in salmon roe and
      the published data suggest that the activity of proteinases may be related to the
      presence of aspartyl proteinases (cathepsin D). Serine proteinases and
      metalloenzymes were not found in roe. The activity of cysteine proteinases was
      low. The proposed conditions of pasteurization favored the complete inactivation
      of salmon roe at pH 6.0-6.4.

PMID- 15553781
TI  - [Chitinolytic activity of filamentous fungi].
AB  - The chitinolytic activity of nine species of filamentous fungi, classified with
      seven genera (specifically, Aspergillus, Penicillium, Trichoderma, Paecilomyces,
      Sporotrichum, Beaueria, and Mucor), was studied. When cultured in liquid medium
      containing 1% crystalline chitin, all fungi produced extracellular chitosans with
      activity varying from 0.2 U/mg protein (Sporotrichum olivaceum, Mucor sp., etc.)
      to 4.0-4.2 U/mg protein (Trichoderma lignorum, Aspergillus niger).

PMID- 15553782
TI  - [N-acetyl-beta-D-hexosaminidase secreted by the marine fungus Phoma glomerata].
AB  - Among the ten strains of marine fungi studied, the mycelial fungus Phoma
      glomerata showed maximum potency in producing N-acetyl-beta-D-glucosaminidase.
      The conditions for fungal growth and enzyme biosynthesis were evaluated. N-acetyl
      beta-D-hexosaminidase was isolated from the culture liquid of Phoma glomerata by
      ion-exchange chromatography (on DEAE-cellulose and DEAE-Sephacell) and gel
      filtration (on Toyopearl HW-55) with a yield of 35%; the enzyme, purified 36.4
      fold, had a molecular weight of 20 kDa. The homogeneity of the enzyme was
      confirmed by gel filtration and SDS-PAGE. Transglycosylation reactions catalyzed
      by the enzyme produced N-acetyl-D-glucosamine and N-acetyl-D-galactosamine with
      respective yields of 38 and 46%.

PMID- 15553783
TI  - [Effect of carbohydrate composition of the cytosol of Aspergillus niger conidia
      on their viability during storage].
AB  - It is shown that the rate of sporogenesis, the appearance of low-molecular-weight
      thiols, and the activation of carbohydrate synthesis in spores adversely affected
      the viability of Aspergillus niger conidia during storage. Conversely, the
      prevalence of trehalose over mannitol and the absence of glycerol, erythritol,
      and glucose in carbohydrate composition facilitated viability of conidia. The
      data obtained are discussed in regard to the biochemical criteria that may be
      used to characterize quiescent state of fungi and retaining the viability of the
      inoculum.

PMID- 15553784
TI  - [Search for yeast producers of brassylic and sebacic fatty acids].
AB  - Yeast cultures belonging to the genera Candida, Torulopsis, Saccharomyces,
      Debaryomyces, Hansenula, Pichia, and Yarrowia, capable of synthesizing brassylic
      and sebacic fatty acids, were screened. Overall, about 200 cultures grown in
      media containing decane or tridecane as a sole source of carbon were tested. On
      the medium with tridecane, yeasts synthesized insignificant amounts of brassylic
      acid. Sebacic acid was produced more intensively in the medium with n-decane. The
      culture Candida tropicalis, displaying the highest ability to synthesize sebacic
      acid, was selected.

PMID- 15553785
TI  - [Conversion of androstenedione and androstadienedione by sterol-degrading
      bacteria].
AB  - The composition of steroid metabolites formed during the conversion of
      androstenedione and androstadienedione, products of degradation of sterol side
      chains by soil and mutant strains of the bacterial genera Mycobacterium and
      Protaminobacter, was studied. Testololactone was absent from the conversion
      products. This favors the idea of different cleavage pathways of steroid ring D
      in bacteria and fungi. Very small amounts of two new 14alpha-hydroxy derivatives
      with cleaved B ring were isolated after conversion of androstenedione by soil
      strains. It was shown that a mutant Mycobacterium smegmatis strain, as well as
      wild strains, could perform 14alpha-hydroxylation of steroids. It is suggested
      that cleavage of the steroid nucleus at the side of rings D and C starts with the
      introduction of a 14alpha-hydroxy group followed by dehydration.

PMID- 15553786
TI  - [Production of surfactants by Rhodococcus erythropolis strain EK-1, grown on
      hydrophilic and hydrophobic substrates].
AB  - The ability of Rhodococcus erythropolis strain EK-1 to produce surfactants when
      grown on hydrophilic (ethanol and glucose) and hydrophobic (liquid paraffins and
      hexadecane) substrates was studied. The strain was found to produce surfactants
      with emulsifying and surface-active properties. The production of surfactants
      depended on the composition of the nutritive medium, nature and concentration of
      the sources of carbon and nitrogen, and duration of cultivation. Chemically,
      surfactants produced by Rhodococcus erythropolis EK-1 grown on ethanol are a
      complex of lipids with polysaccharide-proteinaceous substances. The lipids
      include glycolipids (trehalose mono- and dicorynomycolates) and common lipids
      (cetyl alcohol, palmitic acid, methyl n-pentadecanoate, triglycerides, and
      mycolic acids).

PMID- 15553787
TI  - [Biological properties of the phosphate-mobilizing Bacillus subtilis strain IMV V
      7023].
AB  - Biological characteristics of a new phosphate-mobilizing bacillus strain are
      reported. Species-level identification of the strain was performed according to
      morphological, cultural, and biochemical characteristics and the sequence of the
      16S rRNA gene. The strain was identified as Bacillus subtilis IMV V-7023 and
      displayed a very high ability to mobilize phosphorus from its sparingly soluble
      inorganic and organic compounds and the capability of synthesizing biologically
      active substances; in addition, the strain essentially suppressed the growth of
      phytopathogenic bacteria, micromycetes, and agents causing various diseases of
      vegetable, cereal, leguminous, and other plants. The strain Bacillus subtilis IMV
      V-7023 is promising for developing bacterial preparations for crop production.

PMID- 15553788
TI  - [Lysozyme of the mollusk Unio pictorum and the sensitivity of alkanotrophic
      rhodococci to its effect].
AB  - A preparation of lysozyme from a freshwater bivalve, Unio pictorum, has been
      isolated by sorption to chitin, and its physicochemical properties have been
      studied. An assessment of the sensitivity of 48 strains of rhodococci, belonging
      to the species Rhodococcus rubber, R. luteus, and R. erythropolis (Specialized
      Collection of Alkanotrophic Microorganisms of the Institute of Ecology and
      Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences),
      which were isolated from diverse natural waters, to lysozyme of the mollusk Unio
      pictorum demonstrated that the three species differ in their sensitivity to its
      effects. The high resistance of rhodococci to lysozyme is indicative of their
      considerable permanence in hydrobiocenoses (and, therefore, ability to maintain
      self-purification of microbiocenoses from hydrocarbons).

PMID- 15553789
TI  - [The significance of exometabolites in the formation and operation of the soybean
      rhizobium symbiosis].
AB  - The effect of various inoculates of the soybean-specific strain of nodule
      bacteria Bradyrhizobium japonicum 634b (unwashed cells, cells washed from the
      exopolysaccharide-protein complex, and cells combined with the complex) on the
      formation and operation of soybean-rhizobium symbiosis. It was shown that
      addition of the exopolysaccharide-protein complex doubled the ability of the
      microsymbiont to form nodules, nodule weight, and the nitrogenase activity of the
      nodules. Bradyrhizobium japonicum 634b cells washed from exometabolites had lower
      indices of symbiotic activity than their intact counterparts.

PMID- 15553790
TI  - [Extracellular polymers in callus cultures of Fagopyrum tataricum (L.) Gaertn.
      with different morphogenic activities: time courses during the culture cycle].
AB  - Time courses of the content of extracellular polymers (ECPs) in culture media of
      morphogenic and non-morphogenic calluses (MCs and NCs, respectively) of Tartar
      buckwheat Fagopyrum tataricum (L.) Gaertn. were studied during the culture cycle.
      It was demonstrated that MCs secreted into the medium much more ECPs compared
      with NCs. During the passage of MCs, two ECPs "blowouts" were observed, which
      preceded formation of proembryonic cell complexes (PECCs). It is supposed that
      the molecules secreted might be involved in PECC recycling in MCs. The maximal
      content of ECPs in NCs was observed by the end of stationary growth phase of the
      culture, which is presumably related to changes in the cell walls during callus
      aging.

PMID- 15553791
TI  - [Effect of salicylic acid on the activity of antioxidant enzymes in wheat under
      conditions of salination].
AB  - The effect of pretreatment with 0.05 mM salicylic acid (SA) on the activity of
      superoxide dismutase (SOD) and peroxidase in the roots of four-day-old seedlings
      of wheat (Triticum aestivum L.) was studied under conditions of salination. The
      level of the stress-induced accumulation of active oxygen species and, therefore,
      activities of SOD and peroxidase in seedlings pretreated with SA were
      significantly lower than in untreated seedlings, which indicates that these
      enzymes contribute to the protective effect of SA on plants under conditions of
      salination.

PMID- 15553792
TI  - [Changes in the biochemical composition, structure, and function of pea leaf
      chloroplasts in iron deficiency and root anoxia].
AB  - A combined effect of iron deficiency and root anoxia on the biochemical
      composition, function, and structure of pea leaf chloroplasts was studied. It was
      found that the chlorosis of apical leaves in response to iron deficiency was
      determined by the reduction of light-harvesting complexes I and II. Under root
      anoxia, complexes of the reaction centers of photosystems I and II degraded
      first. Weak activity was preserved even in yellow and white leaves under the
      effect of both factors. The ultrastructure of leaf chloroplasts gradually
      degraded. Initially, intergranal thylakoid sites were reduced, and the
      longitudinal orientation of grana was disturbed. However, yellow and white leaves
      still retained small thylakoids and grana. It is concluded that the degrading
      effects of iron deficiency and root anoxia on the complex composition and leaf
      chloroplast structure and function are additive because of their autonomous
      mechanisms.

PMID- 15553793
TI  - [Fractional isolation and study of the structure of galactomannan from sophora
      (Styphnolobium japonicum) seeds].
AB  - Two fractions (1 and 2) of the galactomannan from seeds of sophora (Styphnolobium
      japonicum) were isolated using cold and hot aqueous extraction with a total yield
      of 12.88%. The two fractions differed by the ratio between mannose (Man) and
      galactose (Gal) residues (4.8:1 and 5.3:1, respectively) and molecular weight
      (1190 and 1400 kDa, respectively). Aqueous solutions of these fractions were
      optically active ([alpha]D +4.80 degrees and -3.36 degrees, respectively) and
      highly viscous ([eta] 1028.8 and 1211.2 ml/g). 13C NMR spectra of both fractions
      were identical with respect to the number and positions of signals, which
      indicates that their primary structures were identical. Using chemical and
      spectroscopic (IR and NMR) methods, it was shown that the galactomannan has a
      main chain consisting of 1,4-beta-D-mannopyranose, some residues of which (16 and
      17% in fractions 1 and 2, respectively) are alpha-galactosylated at the C-6
      position. Frequencies of differently substituted mannobiose blocks in the chain,
      calculated for fraction 1 using NMR spectroscopic data, were 0.13 for the
      disubstitited blocks Gal(Man-Man)Gal, 0.37 for the sum of monosubstituted blocks
      Gal(Man-Man) and (Man-Man)Gal, and 0.50 for the unsubstituted block Man-Man.

PMID- 15553794
TI  - [Interaction of the immune system of the organism with saprotrophic opportunistic
      microflora and possible coupling of the process with the metabolic status of
      humans].
AB  - The article sets forth the concept of natural biospheric immunization of a
      macroorganism by opportunistic saprotrophic microflora. Immunization by
      opportunistic microflora and microbial control of the metabolic status (which is
      coupled to the immune status of the organism) may act in a concert to provide
      immune defense. Efficient immunization requires that normal microflora be
      certified and the patients, phenotyped by the type and rate of xenobiotic
      biotransformation (via oxidation and acetylation). Data from the literature,
      based on which the suggested measures to stimulating the immune defense of the
      organism should be taken, are analyzed.

PMID- 15553796
TI  - Osteoporosis and periodontal disease.

PMID- 15553795
TI  - Human brain processing and central mechanisms of pain as observed by electro- and
      magneto-encephalography.
AB  - We review the recent progress of electroencephalography (EEG) and
      magnetoencephalography (MEG) to elucidate pain perception mechanisms in humans,
      since EEG and MEG have an excellent temporal resolution in order of msec. MEG is
      more useful to detect activated areas following painful stimulation, because the
      spatial resolution of EEG is not very high. For recording activities following
      Adelta fiber stimulation relating to the first pain, painful CO2 laser
      stimulation is now widely used, but our new method, epidermal stimulation (ES),
      is also very useful. The primary small activity was recorded from the primary
      somatosensory cortex (SI), probably in area 1, in the hemisphere contralateral to
      the stimulation. Then, secondary somatosensory cortex (SII) and insula were
      activated with the second activity in SI. These 3 regions were activated in
      parallel with almost the same time period. This is a very characteristic finding
      in pain perception. Then, the cingulate cortex and medial temporal area (MT)
      around the amygdala and hippocampus were activated. In the hemisphere ipsilateral
      to the stimulation as well, the above regions were activated, except for SI.
      Therefore, we speculated that SI plays a main role in localization of the
      stimulus point, the SII and insula are important sites for pain perception, and
      the cingulate and MT are mainly responsible for cognitive or emotional aspects of
      pain perception. For recording activities following C fiber stimulation relating
      to the second pain, we recently developed a new method, that is, applying weaker
      CO2 laser stimuli to tiny areas of the skin. MEG findings following C fiber
      stimulation were also similar to those following Adelta fiber stimulation.
      However, the effects of sleep and attention on MEG following C fiber stimulation
      was much larger than that following Adelta fiber stimulation. This finding may
      suggest greater effects of cognitive or emotional functions on second pain than
      the first pain.

PMID- 15553798
TI  - White blood cell and platelet counts could affect whole blood viscosity.
AB  - BACKGROUND: Blood viscosity is correlated with cerebral blood flow and cardiac
      output, and increased viscosity may increase the risk of thrombosis or
      thromboembolic events. The relationship between hematocrit and viscosity is well
      known, however, the relationships between white blood cell (WBC) or platelet
      count and viscosity were not fully studied. The aim of the present study was to
      determine the influences of platelet count and WBC count on blood viscosity.
      METHODS: One-hundred and 13 subjects with different hemoglobin, WBC and platelet
      count were enrolled into the study. The variables measured included serum
      fibrinogen, cholesterol, triglyceride, high-density lipoprotein (HDL), low
      density lipoprotein (LDL), complete blood counts including hemoglobin,
      hematocrit, platelet count, red blood cell (RBC) count, WBC count, whole blood
      and plasma viscosity. The relationships of these variables with whole blood or
      plasma viscosity were analyzed. RESULTS: Serum fibrinogen, cholesterol,
      triglyceride, HDL and LDL did not correlate with whole blood viscosity. Not only
      hematocrit, hemoglobin and RBC, but also WBC and platelet count, could affect
      whole blood viscosity. On the other hand, none of the variables could affect
      plasma viscosity. CONCLUSIONS: All the blood cell components, but not the plasma
      proteins detected above, could affect whole blood viscosity. When patients are
      with high leukocytosis and thrombocytosis, impaired blood viscosity should also
      be considered to obtain appropriate clinical management.

PMID- 15553797
TI  - Periodontal status in post-menopausal osteoporosis: a preliminary clinical study
      in Taiwanese women.
AB  - BACKGROUND: Osteoporosis and periodontitis are common diseases affecting post
      menopausal women; however, the exact relationship between the diseases is still
      uncertain. The purposes of this study were to examine the periodontal status in a
      group of type I post-menopausal women with and without osteoporosis and to
      elucidate the possible role of the osteoporosis in the pathogenesis of
      periodontal disease. METHODS: Thirty-four patients (18 in the osteoporotic and 16
      in the non-osteoporotic group) were selected from 329 post-menopausal Taiwanese
      women who had completed radiographic measurements of spinal bone mineral density
      and received full-mouth periodontal examination. Periodontal measurements,
      including O'Leary plaque index, probing depths, clinical attachment level, and
      gingival recession, on 6 sites of each tooth of full mouth were examined and
      recorded by 1 examiner. RESULTS: Significantly greater probing depth was noted at
      the interproximal, but not at the facio-lingual, osteoporotic sites if compared
      to those non-osteoporotic sites. The depth was also significantly influenced by
      the examining factors of plaque accumulation, tooth location, and jaws. By
      individual jaw, increased attachment loss accompanied by greater probing depth
      and gingival recession was found at the osteoporotic sites on mandible if
      compared to non-osteoporotic sites. On maxilla, however, less gingival recession
      and attachment loss were observed at the osteoporotic sites. CONCLUSIONS: In the
      present study, increased attachment loss accompanied by greater probing depth and
      gingival recession was found at the osteoporotic sites on mandible. However, the
      parameters were also influenced by the examining factors of plaque accumulation,
      tooth location, and jaws. Therefore, we suggest that post-menopausal osteoporosis
      may play a role in the pathogenesis of periodontal disease, especially on the
      mandible, although the etiology of periodontal disease is still multi-factorial.

PMID- 15553799
TI  - Postoperative spinal deep wound infection: a six-year review of 3230 selective
      procedures.
AB  - BACKGROUND: Postoperative wound infection remains a troublesome but common
      complication after spinal surgery. This study presents the 6-year experience of
      our surgical team with post-operative deep wound infection in Taipei Veterans
      General Hospital. METHODS: Of 3230 selected operations, 72 cases of wound
      infection were identified. Thirty patients with deep wound infection were
      reviewed, including 17 men and 13 women at a mean age of 32 years. The pre
      operative diagnoses included spondylolisthesis, scoliosis, spinal stenosis,
      herniated inter-vertebral disc, spinal fracture and adjacent syndrome. RESULTS:
      In this report, different deep wound infection rates were compared between
      different operative procedures including (1) posterior decompression with
      fixation and fusion, 1.15%. (2) simple decompression (laminectomy) and disectomy,
      0.37%, (3) revision fixation with decompression, 4.4%, and (4) removal of
      implant. 0.33%. The onset of infection sign was divided into 3 groups: (1) acute
      (< 2 weeks), 43.3%, (2) subacute (2-4 weeks), 40%, and (3) chronic (> 4 weeks),
      16.6%. In 11 patients with deep wound infection, no bacteria was cultured, while
      14 patients had Methicillin-resistant Staphylococcus aureus and another 3
      patients had lower-grade toxic Staphylococcus aureus. All patients received
      debridement followed by delayed wound closure with effective antibiotics.
      Instruments were removed in only 8 patients. Twenty seven cases were cured after
      treatment but 3 patients expired in poor condition. CONCLUSIONS: In this series,
      total deep wound infection was 0.9% in our 6-year experience. The incidence of
      postoperative spinal infection increased with the complexity of the procedure.
      Most patients got completely disease free with antibiotics and surgical
      treatment.

PMID- 15553800
TI  - Determining factors of patient satisfaction for frequent users of emergency
      services in a medical center.
AB  - BACKGROUND: The present era of a competitive healthcare environment indicates
      that providers have been convinced that attentiveness to patient satisfaction is
      integral to care quality and market share. Patient satisfaction is especially
      critical for frequent users of the emergency department (ED). The aim of this
      study was to compare satisfaction of overall ED care between frequent and
      infrequent ED users, and to find out the factors determining satisfaction among
      the frequent ED users. METHODS: Frequent ED users (> or = 4 visits/per year) and
      infrequent ED users (< 4 visits/per year) were selected randomly from patients
      visiting the adult ED of a public tertiary medical center from October 1, 2000 to
      September 30, 2001. Retrospective telephone interviews were completed for 200
      frequent users and 200 infrequent users. Ordinal logistic regression analysis was
      performed. RESULTS: Infrequent ED users tended to give a higher satisfaction
      rating than frequent ED users to emergency care (OR = 2.14; 95% CI = 1.40-3.25).
      The 2 significant determinants associated with satisfaction with emergency care
      among frequent ED users were discharge instructions (OR = 2.78; 95% CI = 1.27
      6.12) and subjective waiting time (OR = 12.6; 95% CI = 4.22-37.8). CONCLUSIONS:
      The frequent ED users were unique, and their satisfaction with overall emergency
      care was significantly lower than that of infrequent ED users. Managing waiting
      time perceptions and providing discharge instructions may be an effective
      strategy to achieve improved patient satisfaction among frequent ED users.

PMID- 15553802
TI  - Venous access port-related nocardia bacteremia with successful short-term
      antibiotics treatment.
AB  - Nocardia infection occurs primarily among patients with deficient cell-mediated
      immunity. The portal of entry in the majority of patients with Nocardia infection
      is pulmonary origin. Central venous catheter-associated bacteremia caused by
      Nocardia species is very rare, and the optimal management for these situations
      was indeterminate. Most patients were cured after discontinuation of central
      venous catheter and prolonged antibiotics use. Thereafter, we reported an 18-year
      old male who received chemotherapy for his nasal rhabdomyosarcoma had central
      venous catheter-associated N. asteroids bacteremia. The outcome was satisfying
      after discontinuation of central venous catheter followed by short-term
      antibiotics. Conclusively, prolonged antibiotics may not be necessary in catheter
      associated Nocardia bacteremia without distant metastatic site after removal of
      catheter.

PMID- 15553801
TI  - Donor lymphocyte infusion induced acute hepatitis.
AB  - Hepatic graft-versus-host disease (GVHD) post allogeneic hematopoietic stem cell
      transplantation generally presents as cholestatic jaundice and increased serum
      alkaline phosphatase (ALK-P). Currently accepted standards for evaluating the
      clinical severity of hepatic GVHD are not based on serum aminotransferase levels
      but on the serum bilirubin levels. We describe a 25-year-old female who initially
      had no liver damage at all after an allogeneic peripheral blood stem cell
      transplantation (allo-PBSCT) from her HLA-indentical sister. Markedly elevated
      aminotransferases, without hyperbilirubinemia, however, developed 7 and 9 weeks
      after the first and second donor lymphocyte infusion (DLI), respectively. Liver
      biopsies performed in both events revealed lymphocytic infiltration of the portal
      tracts and pericentral necrosis of the lobuli. There was also a picture of
      periductal lymphocytic infiltration and vacuolization of the biliary epithelial
      cells, which was compatible with the diagnosis of GVHD of cholangiohepatitic
      type. These findings indicate that hepatic GVHD may present as acute hepatitis
      and should be included in the differential diagnosis for patients with increased
      aminotransferases after DLI.

PMID- 15553803
TI  - Computed tomographic findings in Lemierre syndrome.
AB  - Lemierre syndrome, also known as postanginal septicemia, has long been taken as
      an uncommon condition with life-threatening potential. It, resulting from acute
      oropharyngeal infection, could lead to septic thrombophlebitis of the internal
      jugular vein (IJV). Substantial decrease of mortality and morbidity with the
      introduction of antibiotics has made this syndrome into a status that is
      frequently forgotten or overlooked when it appears. The purpose of this article
      is to refresh awareness on the side of physicians of this syndrome by means of
      modern image tools. As such, even this dire neck infection is rare after the
      advent of sophisticated antibiotics, its unique computed tomography findings can
      facilitate the correct image diagnosis and pertinent treatment.

PMID- 15553804
TI  - Urinary exenteration on a renal transplant recipient with multifocal urothelial
      cancers and prostatic adenocarcinoma.
AB  - The two cancers after renal transplantation (RTx) are transitional cell carcinoma
      (TCC) and hepatoma reported in Taiwan most frequently, versus lymphproliferative
      diseases and skin cancers in the Western literature. Herein, we present a 49-year
      old man with spinal cord injury and end-stage renal disease who developed
      multifocal TCC in the urologic tract and incidental detection of prostatic
      adenocarcinoma 15 months after a cadaveric RTx. En bloc complete native urinary
      tract excision and ileal conduit urinary diversion were performed smoothly. After
      2-year follow up, there was no evidence of tumor recurrence, and graft function
      remained stable, with minimal hydronephrosis. Transplant physicians should
      carefully monitor any signs of urinary cancers, especially in renal transplant
      recipients with history of analgesics. Also, aggressive surgical treatment is
      recommended for these patients to prolong survival.

PMID- 15553805
TI  - Air bag associated posterior segment ocular trauma.
AB  - Airbags indeed reduce the risk of injury and death in motor vehicle accidents,
      however, ocular injury induced by airbag deployment has been reported. From 1999
      to 2001, medical records were retrospectively reviewed for patients with severe
      ocular injury related to airbag inflation at Taipei Veterans General Hospital.
      The ocular presentation, clinical course, management and visual outcome were
      recorded and studied in detail. Three cases of ocular posterior segment injury
      associated with airbag inflation were identified. Mean age was 37.3 years old
      (range 34-39 years). None of the patients was wearing a seat belt. All patients
      had periocular contusion, corneal edema, and hyphema. Vitreous hemorrhage was
      found in 3 cases, and there were 2 cases with severe macular injury, including
      traumatic maculopathy and hypotony maculopathy. Retinal detachment developed in 1
      case. One patient presented with traumatic macular hole 6 weeks after injury. The
      initial visual acuity was hand motion only in all patients, the final visual
      outcomes recovered to 6/20, 1/60 and 2/60, respectively. The airbag-associated
      posterior segment ocular trauma was induced by impact with fully deployed airbag.
      Severe ocular posterior segment trauma with devastating visual sequelae might
      occur in drivers and passengers who have not fastened their seat belt.

PMID- 15553806
TI  - The benefit of arthroscopy for symptomatic total knee arthroplasty.
AB  - Thirty-one knees with symptomatic total knee arthroplasty were diagnosed and
      treated arthroscopically. There were 18 knees with soft tissue impingement and 13
      knees without. There were 16 knees with painful arthroplasty and range of motion
      (ROM) greater than 90 degrees. Hypertrophied synovitis with or without
      impingement was more easily found by arthroscopy in this group than in the other
      15 knees with the chief complaint of limited ROM, where more remarkable fibrotic
      tissue with intra-articular adhesion was found. Overall, the average improvement
      in ROM was 43.1 degrees immediately after arthroscopy, and 20 degrees at the
      final follow-up. Symptoms improved in 90.3% of patients, and 58.1% were satisfied
      with the outcome of their surgery. Arthroscopy is helpful for intra-articular
      diagnosis, obtaining a specimen for histopathologic analysis, culture for
      subclinical infection, and better improvement in ROM. In our experience,
      arthroscopy for symptomatic knee arthroplasty is reliable, safe and effective.

PMID- 15553807
TI  - Cognrrive biases for emotional faces in high- and low-trait depressive
      participants.
AB  - This study examined the association between trait depression and information
      processing biases. Thirty participants were divided into high- and low-trait
      depressive groups based on the median of their depressive subscale scores
      according to the Basic Personality Inventory. Information-processing biases were
      measured using a deployment-of-attention task (DOAT) and a recognition memory
      task (RMT). For the DOAT, participants saw one emotional face paired with a
      neutral face of the same person, and then were forced to choose on which face the
      color patch had first occurred. The percentage of participants' choices favoring
      the happy, angry, or sad faces represented the selective attentional bias score
      for each emotion, respectively. For the RMT, participants rated different types
      of emotional faces and subsequently discriminated old faces from new faces. The
      memory strength for each type of face was calculated from hit and false-positive
      rates, based on the signal detection theory. Compared with the low-trait
      depressive group, the high-trait depressive group showed a negative cognitive
      style. This was an enhanced recognition memory for sad faces and a weakened
      inhibition of attending to sad faces, suggesting that those with high depressive
      trait may be vulnerable to interpersonal withdrawal.

PMID- 15553808
TI  - Too late to quit? Effect of smoking and smoking cessation on morbidity and
      mortality among the elderly in a longitudinal study.
AB  - This prospective study of the elderly population estimated the risks of smoking
      for morbidity and mortality and identified whether cessation of smoking reduced
      the risk of disease. Data came from face-to-face interviews that used a
      population-based probability sample of those aged 60 years or over in Taiwan,
      provided by the Population and Health Research Center, Bureau of Health
      Promotion. In total, 4,049 subjects were included at the baseline year of 1989
      and followed up in 1993 and 1996. Smoking-related variables included current
      smoking status, smoking history, daily consumption, and years since the cessation
      of smoking. Cox regression models were used to analyze the relative risks for
      morbidity and mortality, controlling for demographics, physical function, and
      comorbidities. The sample was made up of 50.2% nonsmokers, 15.2% ex-smokers, and
      34.6% current smokers in the baseline year. Current smokers were more likely to
      have lower respiratory tract diseases throughout the study. Current smokers had a
      higher risk of stroke from 1989 to 1993. No dose-response relationship for
      smoking exposure or impact of years since smoking cessation was found. Whether
      cessation of smoking is protective should be investigated for middle-aged adults
      followed to old age. An effective strategy for smoking cessation in the elderly
      is suggested, and people should be encouraged to quit smoking at any time.

PMID- 15553809
TI  - Concerns and recommendations of internal medicine residents in HIV patient care
      in the second decade of the AIDS epidemic in Taiwan.
AB  - Internal medicine residents are usually on the front line of caring for HIV
      infected patients. In the second decade of the AIDS epidemic in Taiwan, a
      qualitative study was conducted to recognize the concerns of internal medicine
      residents in caring for HIV/AIDS patients and to identify possible strategies to
      promote HIV patient care that have not been addressed in previous research.
      Individual in-depth interviews were conducted with 47 internal medicine residents
      at a university hospital in Taiwan. Seven factors (stereotypes of AIDS; fear of
      transmission; concerns of families, friends, and colleagues; lack of clinical
      expertise; lack of collegial support; lack of a sense of accomplishment; and lack
      of worker's compensation if infected) were found to be the chief concerns of
      participants in providing HIV/AIDS care. Four strategies (education, clinical
      experience, safe working environment, and employee benefits) were voiced as those
      that could promote health care professionals' well-being and willingness to
      provide HIV/AIDS care. The results of this study are explained in light of the
      historical, social, and medical contexts in Taiwan.

PMID- 15553810
TI  - Duodenal obstruction after elective abdominal aortic aneurysm repair: a case
      report.
AB  - Gastrointestinal tract complications after abdominal aortic aneurysm (AAA) repair
      are well known. The reported frequency ranges from 6.6% to 21%. However, the
      incidence of duodenal obstruction following AAA has probably been underestimated.
      This report concerns a 78-year-old male who was admitted for elective repair of
      an infrarenal AAA. On the ninth postoperative day, the patient presented with
      large quantities of bile-stained vomitus despite passing flatus per rectum.
      Metoclopramide and ranitidine were given under the initial impression of
      paralytic ileus. However, the upper gastrointestinal obstruction persisted, and
      on day 12, computerized tomography (CT) revealed marked distension of the gastric
      tube and duodenum, down to the level of the third portion, with abrupt change of
      caliber at the point of the superior mesenteric artery (SMA). SMA syndrome was
      diagnosed. After nasogastric tube aspiration, parenteral nutrition, and 11 days
      of conservative treatment, abdominal CT and upper gastrointestinal series showed
      no apparent duodenal obstruction. The patient was discharged on the 29th
      postoperative day; follow-up abdominal CT 4 months later was unremarkable.

PMID- 15553811
TI  - Chloroma of the testis after allogeneic peripheral blood stem cell
      transplantation: a case report.
AB  - Chloroma, or granulocytic sarcoma, is a rare extramedullary solid hematologic
      cancer that affects many sites, usually in concert with acute myeloid leukemia.
      It is infrequently associated with other myeloproliferative disorders or chronic
      myelogenous leukemia. Chloroma of the testis after allogeneic bone marrow
      transplantation is particularly sparsely represented in the literature. It is
      often incorrectly diagnosed as malignant lymphoma, especially large-cell
      lymphoma, owing to the similarity of the histologic morphology, scanty
      eosinophilic myelocytes, and no or overlooked history of leukemia. Although
      erroneous diagnosis is decreasing with the advent of ancillary studies, the
      diagnosis of chloroma continues to be a nightmare for pathologists. It is thus
      suggested that an appropriate panel of marker studies be performed in conjunction
      with clinical correlation and circumspection to avoid reaching a misleading
      conclusion and improper treatment of patients. We report an interesting case of a
      35-year-old male with a clinical history of chronic myelogenous leukemia post
      allogeneic peripheral blood stem cell transplantation and complete molecular
      remission, who was found to have chloroma of the left testis.

PMID- 15553812
TI  - Acute necrotizing ureteritis with obstructive uropathy following instillation of
      silver nitrate in chyluria: a case report.
AB  - Chyluria occurs as a result of communication between the lymphatics and the renal
      pelvis. It is believed that instillation of silver nitrate into the renal pelvis
      is a safe, minimally invasive and effective treatment for chyluria. We report an
      unusual complication of acute necrotizing ureteritis following instillation of
      silver nitrate in a case of chyluria. It resolved completely with non-surgical
      intervention. The diagnosis and management of chyluria is discussed, with a brief
      review of the literature.

PMID- 15553814
TI  - [Program for diagnosis and treatment of liver cirrhosis with integrative Chinese
      and Western medicine (draft)].

PMID- 15553813
TI  - Clinical evaluation of a new bilayer artificial dermis for repair of oral mucosal
      defects: report of two cases.
AB  - Free mucosal grafts or split-thickness skin grafts have been used in patients
      undergoing repair procedures for oral mucosal defects. Conventional methods
      require the creation of second surgical wounds for use as donor sites. We applied
      two bilayers of artificial dermis to repair a buccal mucosal defect in one case
      and vestibular extension in another case. After removal of the sutures, no
      infection, pain, or hemorrhage developed in these patients. The results of
      granulation and epithelialization were good. Satisfactory appearance and function
      were achieved in both cases. Therefore, bilayer artificial dermis may be
      recommended for the repair of oral mucosal defects.

PMID- 15553815
TI  - [Study on relationship among thyroid hormone relativity and Syndrome
      Differentiation-types of TCM in patients with congestive heart failure].
AB  - OBJECTIVE: To study the relationship between the TCM Syndrome Differentiation
      types of congestive heart failure (CHF) and thyroid hormones, including
      triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), and
      atrial natriuretic peptide (ANP), as well as cardiac function parameters,
      including left ventricular ejection fraction (LVEF), mean velocity of
      circumferentid fiber shortening (mVcf) and A peak/E peak (A/E). METHODS: One
      hundred patients with CHF were divided into 4 Syndrome Differentiation-type
      groups, their cardiac function parameters, ANP and thyroid hormones were
      determined and compared with those in the 23 subjects in the control group.
      RESULTS: In CHF patients with edema and blood stasis Syndrome type, the level of
      plasma ANP was significantly higher than that in the control group (P < 0.05);
      level of T3 was significantly lower than that in the control group and in CHF
      patients of other three (Xin-qi deficiency, Yin-deficiency and blood stasis)
      Syndrome groups (P < 0.01, P < 0.01, P < 0.05 and P < 0.01); levels of LVEF and
      mVcf were significantly lower than those in the other three Syndrome groups (all
      P < 0.01). Level of T4 in other three Syndrome groups significantly increased
      than that in the edema and blood stasis Syndrome type. A/E value showed a higher
      level in patients of all TCM type than that in the control (P < 0.01).
      Correlation analysis showed that T3 was positively correlated with LVEF and T4 (r
      = 0.200, P < 0.05, and r = 0.293, P < 0.01), and negatively correlated with ANP
      (r = -0.263, P < 0.01); T4 was negatively correlated with A/E (r = -0.226, P <
      0.05). CONCLUSION: The lowering of T3 and T4 and increasing of ANP may be one of
      the important reasons for lowering of LVEF in CHF patients with edema and blood
      stasis Syndrome-type. The decrease of T4 may be one of the important reasons for
      elevation of A/E and aggravation of left ventricular diastolic dysfunction in CHF
      patients of all the 4 TCM Syndrome-types.

PMID- 15553816
TI  - [Study on relationship between TCM Syndrome types (Xin-qi and Xin-yang
      deficiency) and contents of cytokines (tumor necrosis factor-alpha and
      interleukins) in patients with congestive heart failure].
AB  - OBJECTIVE: To explore the relationship between TCM Syndromes types, Xin-qi
      deficiency (XQD) and Xin-yang deficiency (XYD), and contents of cytokines,
      including tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta
      and IL-10 in patients with congestive heart failure (CHF). METHODS: Sixty-seven
      CHF in-patients with Xin-qi deficiency or Xin-yang deficiency syndrome were
      enrolled, their NYHA (New York Heart Association) cardiac function was assessed,
      ejection fraction (EF) and E peak/A peak (E/A) ratio were determined by Doppler
      ultrasonic echocardiograph, and serum TNF-alpha, II-6, IL-1beta and IL-10 were
      measured by double antibody sandwich ELISA assay. RESULTS: The cardiac function
      grading in patients of XQD was mostly of I and II grade, while that in patients
      of XYD was mostly of III and IV grade (by Ridit analysis, P<0.01). The E/A and EF
      values were higher in patients of XQD than those in patients of XYD (P<0.01).
      Levels of TNF-alpha, IL-6 and IL-1beta were higher and IL-10 was lower in
      patients of XYD than those in patients of XQD (P<0.05 or P<0.01) respectively.
      CONCLUSION: TNF-alpha, IL-6, IL-1beta and IL-10 probably play an important role
      in the development process of XQD to XYD, and could be taken as the microcosmic
      indexes for differentiation of the two syndromes.

PMID- 15553817
TI  - [Effect of shuxuetong in preventing restenosis after intracoronary stenting].
AB  - OBJECTIVE: To evaluate the effect of shuxuetong (SXT) in preventing restenosis
      after intracoronary stenting. METHODS: Sixty-eight patients, accepted
      intracoronary stenting, were divided into two groups, the SXT group and the
      control group, both of them were treated with conventional treatment, and to the
      SXT group, SXT was given additionally. The condition of treated coronary artery
      restenosis in the two groups was compared by way of quantitative coronary
      angiography and a 6-month follow-up study was adopted. RESULTS: Follow-up study
      was completed in 43 patients (23 cases in the SXT group, and 20 in the control
      group). The angina recurrence rate in the SXT group (3 cases, 13%) was
      significantly lower than that in the control group (7 cases, 35%, P < 0.05).
      Quantitative coronary angiography showed the restenosis degree of operated artery
      in the SXT group was significantly milder than that in the control group, with
      the last lumen losing and index in the SXT group (0.46 +/- 0.25 mm, 24.26 +/-
      8.64%) less than those in the control group (0.75 +/- 0.33 mm, 31.25 +/- 11.03%).
      The net gain lumen and the net gain index in the SXT group (1.23 +/- 0.30 mm,
      58.96 +/- 24.68%) were greater than those in the control group (0.98 +/- 0.33 mm,
      42.68 +/- 29.51%), all P < 0.05. But the restenosis rate in the two groups was
      insignificantly different (P > 0.05). CONCLUSION: SXT might has some definite
      effect in preventing restenosis after intracoronary stenting.

PMID- 15553818
TI  - [Effect of compound Salvia injection on blood coagulation in patients with
      traumatic cerebral infarction].
AB  - OBJECTIVE: To investigate the effect of compound Salvia injection (CSI) on blood
      coagulatory function in patients with traumatic cerebral infarction (TCI).
      METHODS: Sixty-four patients with TCI were randomly divided into two groups, 32
      in each group. The treated group were treated with CSI plus conventional
      treatment of western medicine, and the control group treated with conventional
      treatment alone. Changes of symptoms, levels of plasma P-selectin (P-S), von
      Willebrand's factor (vWf) and D-dimer were observed with ELISA. RESULTS: The
      treated group was superior to the control group in Glasgow outcome scale (P <
      0.01). Before treatment, the levels of plasma P-S, vWf and D-dimer in the TCI
      patients were higher than those in healthy people. After treatment, all the
      parameters lowered in both groups, but the effect of lowering was greater in the
      treated group than that in the control group. CONCLUSION: Blood coagulation
      disorder exists in patients with TCI, CSI could improve it, and might alleviate
      the cerebral damage to a certain extent.

PMID- 15553819
TI  - [Intervention effect of tongfei mixture on nocturnal hypoxia in patients with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To study the effect of tongfei mixture (TFM, a Chinese recipe mainly
      consisted of angelica and rehmannia root) on nocturnal hypoxia in patients with
      chronic obstructive pulmonary disease (COPD). METHODS: Sixty patients with COPD
      of remission phase were randomly divided into 3 groups, 20 in each group. Group A
      was the control group; Group B, the group simply treated with oxygen; Group C,
      treated with oxygen and TFM. Changes of pulmonary function, diaphragm muscle
      mobility (DMM), 6 min walk distance (6MWD), morning arterial blood gas, nocturnal
      lowest oxygen saturation (LSaO2), mean blood oxygen saturation (MSaO2), the
      percentage of saturation lower than 90% time account for total sleeping time
      (SLT90%) and ultrasonocardiogram before and after treatment were observed.
      RESULTS: Levels of LSaO2, MSaO2 and SLT90% in Groups B and C were significantly
      higher than those in Group A (P<0.05, P<0.01). The lowering of PaCO2 in Group C
      was more significant than that in Group B (P<0.05). The mPAP level in Group C was
      lower, FEV1, 6MWD and DMM were improved than those in Group A and B, showing
      significant difference (P<0.05). CONCLUSION: Combined use of oxygen therapy and
      TFM could not only improve the nocturnal hypoxia, but also lower PaCO2. TFM is an
      important supplement of oxygen therapy.

PMID- 15553820
TI  - [Study on treatment of climacteric depression with bushen tiaogan qingxin
      recipe].
AB  - OBJECTIVE: To observe the effects of bushen tiaogan qingxin recipe (BTQR) on
      Hamilton rating scale for depression (HAMD), monoamine meurotransmitter and
      endocrinal function in patients with climacteric depression, and to explore its
      mechanism. METHODS: Patients were randomly divided into two groups, the 25
      patients in the treated group treated with BTQR and 15 patients in the control
      group treated with hormone replacement therapy (HRT). The HAMD scoring, levels of
      5-HT, NE in plasma, serum estradiol (E2), follicle-stimulating hormone (FSH),
      luteinizing hormone (LH) were determined before and after treatment, and the
      thickness of endometrium was measured by B-Doppler ultrasonographic technique.
      RESULTS: The total effective rate, evaluated by the HAMD score reducing rate, in
      the treated group was 87.2%, and in the control group was 67.3%, showing
      significant difference (P<0.05). After treatment, 5-HT decreased (P<0.01), NE
      increased (P<0.05) and 5-HT/NE ratio lowered (P<0.01) in the treated group; E2
      increased in both groups; FSH, LH and FSH/LH ratio decreased in the treated group
      (P<0.05 or P<0.01), FSH/LH ratio decreased in the control group (P<0.05). The
      thickness of endometrium increased in the control group after treatment (P<0.05).
      CONCLUSION: The mechanism of BTQR in treating climacteric depression might be
      related with its actions in: (1) To regulate the synthesis and release of
      monoamine neurotransmitter; (2) To adjust reproductive endocrine function; (3) To
      coordinate the neuroendocrinal function.

PMID- 15553821
TI  - [Study on treatment of iron-deficiency anemia by shengxuening].
AB  - OBJECTIVE: To observe the therapeutic effect of shengxuening (SXN) in treating
      iron-deficiency anemia (IDA) and to explore its molecular mechanism on iron
      metabolism balance regulation. METHODS: Patients with IDA were randomly divided
      into the treated group and the control group, 50 in each group. They were treated
      with SXN (0.1 g, three times per day) and ferrous gluconate (0.1 g, three times
      per day) respectively, for 30 days. Levels of serum iron (Fe), total iron binding
      capacity (TIBC), transferrin saturation (TS), serum ferritin (SF), transferrin
      (Tf), soluble transferrin receptor (sTfR) and blood routine test, as well as
      scoring of TCM qi-blood deficiency Syndrome were conducted before and after
      treatment. RESULTS: The total effective rate in the treated group reached 92%, it
      was shown that SXN could improve the iron metabolism, increase levels of Fe, TS,
      SF and reduce levels of TIBC, Tf, sTfR, it has obvious effect in promoting
      erythrocyte generation and could promote formation of leucocytes and platelets.
      The total effective rate in the control group was 32%, which was significantly
      lower than that in the treated group (P < 0.01). CONCLUSION: The effect of SXN in
      treating IDA and qi-blood deficiency Syndrome is evident, it could improve the
      iron metabolism, increase levels of Fe, TS, SF and lower levels of TIBC, Tf,
      sTfR.

PMID- 15553822
TI  - [Expression of HSP70 and P53 in malignant tumor tissues and its relationship to
      heat syndrome of TCM].
AB  - OBJECTIVE: To investigate the expression of HSP70 and P53 in malignant tumor
      tissues of patients with TCM Heat-Syndrome (HS) or with non-Heat-Syndrome (NHS).
      METHODS: S-P immunohistochemical method was used to detect the gene expression,
      and ELISA and RT-PCR were adopted to determine the content of HSP70 and P53 mRNA
      expression in different malignant tumor tissues. RESULTS: (1) Positive ratio of
      HSP70 and P53 in the colorectal cancer of HS was significantly higher than that
      in colorectal cancer of NHS respectively, and the total positive ratio of the two
      genes in all tumors of HS was higher than those of NHS (P<0.05); (2) HSP70
      expression content in colorectal, nasopharyngeal and lung cancers of HS was
      higher than in those of NHS respectively, and the total HSP70 expression content
      in tumors of HS was higher than in those of NHS (P<0.01); (3) HSP70 mRNA
      expression content in colorectal and lung cancers of HS was higher than in those
      of NHS respectively, and the total HSP70 mRNA expression content in tumors of HS
      was higher than in those of NHS (P<0.01). CONCLUSION: HSP70 and P53 positive
      ratio and HSP70 expression content in patients of malignant tumor with HS was
      higher than in those with NHS.

PMID- 15553824
TI  - [Analysis of clinical characteristic in type 2 diabetes mellitus patients of
      different syndrome differentiation].

PMID- 15553823
TI  - [Effect of shenqi fuzheng injection for assistance of chemotherapy in treating
      senile patients with non-small cell lung cancer].
AB  - OBJECTIVE: To study the effect of chemotherapy assisted with shenqi fuzheng
      injection (SFI) on senile patients with non-small cell lung cancer (NSCLC).
      METHODS: One hundred and twenty old patients with NSCLC were treated with NP
      chemotherapeutic protocol, to the 60 patients in the treated group among them,
      additional medication of SFI was started one week before the beginning of
      chemotherapy. The short-term therapeutic efficacy, long-term survival rate,
      changes on quality of life (QOL) and immune function of patients, and
      hematological toxicity of therapy were observed. RESULTS: Difference between the
      two groups on short-term therapeutic effect, 1- and 2-year survival rate showed
      no significance (P>0.05), but the 3-year survival rate in the treated group was
      26.6%, while that in the control group was 11.7%, showed that the former was
      higher than the latter. After treatment QOL of the treated group was better than
      that of the control (P<0.05). Besides, the hematological toxicity and affection
      on immune function of chemotherapy after treatment in the treated group were all
      lower than those in the control group showing significant difference (P<0.05).
      CONCLUSION: SFI has definite toxicity relieving effect on chemotherapy in
      treating senile NSCLC.

PMID- 15553825
TI  - [Effect of tetramethylpyrazine on lipopolysaccharides induced macrophage cyclo
      oxidase-2 expression and apoptosis of cardiac myocytes].
AB  - OBJECTIVE: To observe the effect of tetramethylpyrazine (TMP) on
      lipopolysaccharides (LPS) induced macrophage cyclo-oxidase-2 (COX-2) gene
      expression and activity in RAW264.7 mice, and to further investigate the effect
      and mechanism of TMP on LPS induced apoptosis of cardiac myocytes in suckling
      mice. METHODS: RT-PCR and Western Blot (WB) were used to investigate the
      macrophage COX-2 gene expression, ELISA was used to measure its activity,
      fluorescence microscopy was used to determine the apoptosis of murine neonatal
      cardiac myocyte, and fluorescence spectrophotometry was used to detect the
      concentration of intracellular calcium ion (Ca2+). RESULTS: TMP of 10(-6) mol/L
      could significantly reduce the COX-2 mRNA and protein expression (P < 0.05), in
      10(-5) mol/L and 10(-4) mol/L could significantly decrease the COX-2 expression
      (P < 0.01) stimulated by LPS, but couldn't influence the activity of COX-2 by
      different TMP concentration. TMP in 10(-5) mol/L could significantly lower the
      concentration of intracellular Ca2+ in cardiac myocyte, and antagonize the LPS
      induced apoptosis of cardiac myocyte in suckling mice (P < 0.05). CONCLUSION: TMP
      has the pharmacological effect in inhibiting LPS induced macrophage COX-2
      expression and apoptosis of cardiac myocyte in suckling mice.

PMID- 15553826
TI  - [Protective effect of tetramethylpyrazine and L-arginine on rats with acute
      myocardial infarction].
AB  - OBJECTIVE: To compare the protective effects of tetramethylpyrazine (TMP) alone
      and TMP and L-arginine (TMP-LA) combination on rats with acute myocardial
      infarction (AMI), and to explore its mechanism. METHODS: The rat model of AMI was
      established by via caudal vein injection of pituitrin. Experimental animal groups
      of normal, model, TMP treated and TMP-LA (via abdominal cavity and caudal vein
      respectively) treated groups were established. Expression of P- and E-selectin,
      serum creatine phosphokinase (CK) and troponin T (TnT), and marrow peroxidase
      (MPO) concentration in myocardial tissue were determined by immunohistochemical
      stain. RESULTS: As compared with the normal group, serum CK and TnT level, and
      MPO concentration in myocardial tissue were significantly higher in the model
      group (P < 0.01), with P- and E-selectin significantly up-regulated (P < 0.01).
      As compared with the model group, the above-mentioned parameters in the TMP or
      TMP-LA treated group was significantly lower (P < 0.05). CONCLUSION: Combined use
      of TMP and LA showed obvious synergism in treating AMI, by way of multi-link
      inhibition on expression of adhesive factors and decrease of leucocyte
      infiltration.

PMID- 15553827
TI  - [Effect of combination of Ginkgo leaf extract and deferoxamine in preventing and
      treating ototoxicity of cisplatin].
AB  - OBJECTIVE: To observe the effect of combined use of jinnaduo (an injection made
      by extract of Ginkgo leaf, EGb) and Deferoxamine (DFO, a chelating agent) in
      antagonizing the ototoxicity of cisplatin (CDDP). METHODS: Guinea pigs were
      randomly divided into the CDDP group, the EGb group, the DFO group, the combined
      treated group (EGb + DFO) and the control group. Changes of auditory brain-stem
      response (ABR), serum superoxide dismutase (SOD) activity and malondialdehyde
      (MDA) content, as well as light and scanning electronic microscopic (SEM) figures
      were observed before and after treatment. RESULTS: The threshold of ABR was
      significantly higher in the CDDP group than that in the other groups (P<0.01),
      but was insignificantly different among the latter groups (P>0.05). Serum SOD
      activity was lower and MDA content was higher in the CDDP group than those in the
      control group (P<0.01), but in comparison of the two parameters between control
      and other groups, the difference was insignificant (P>0.05). SEM examination on
      cochlea showed that the damage of hair cells was milder in the DFO group and the
      combined treated group than that in the CDDP group, which was slightly milder in
      the EGb group than that in the CDDP group. CONCLUSION: Combined use of EGb and
      DFO could effectively reduce the ototoxicity of CDDP, its effect is better than
      using EGb singly, and similar to that of using DFO alone. The combination could
      also prevent the side-effect of CDDP in bone marrow inhibition. The Fe ion
      participated free radical response could be one of the mechanisms of CDDP in
      damaging hearing.

PMID- 15553828
TI  - [Study on sero-pharmacology of fresh Gecko Swinhonis Gunther freeze-dried powder
      in inducing cell apoptosis of C6 glioma cells in mice].
AB  - OBJECTIVE: To explore the effect of Gecko Swinhonis Gunther freeze-dried powder
      (GFP) in inducing apoptosis of C6 glioma cells. METHODS: Thirty mice were
      randomly divided into three groups and treated with intraperitoneally injection
      of cisplatin, orally taken GFP or distilled water respectively. After treatment
      for 20 days, the serum of mice was collected for treating the C6 glioma cells.
      The apoptosis state of cells was observed by morphological examination, flow
      cytometry and TUNEL method, and the cell apoptosis related gene expression of bcl
      2 and bax were determined by S-P immunocytochemical assay. RESULTS: The C6 glioma
      cell apoptosis induction of GFP contained serum in vitro could be confirmed by
      morphological examination, flow cytometry analysis and TUNEL method. Comparison
      between the GFP treated group and the blank control group on intracellular bcl-2
      gene expression showed no difference, but bax gene expression was higher in the
      GFP treated group. CONCLUSION: GFP contained serum could induce C6 glioma cell
      apoptosis, its mechanism might be related with the up-regulation of bax gene.

PMID- 15553829
TI  - [Study on effect of arsenic trioxide on adhesion and invasion of human
      hepatocarcinoma cells in vitro].
AB  - OBJECTIVE: To explore that the arsenic trioxide injection (ATI) has the effect in
      antagonizing adhesion and invasion of human hepatocarcinoma cells (HCC), and its
      relevant mechanism. METHODS: Human hepatocellular carcinoma cell line SMMC-7721
      and the high metastatic nude mice human HCC in situ transplantation model was
      taken as the objects of study, the effects of ATI on the SMMC-7721 cell movement
      and migration, its adhesion with fibronectin (FN) and endothelial cell (EC), as
      well as the CD44 and MMP-2 gene protein expression in transplanted tumor of the
      model mice were observed by means of cell movement and migration test, cell
      adhesion test and immunohistochemical method. RESULTS: ATI could significantly
      inhibit SMMC-7721 cell movement and migration on FN, adhesion with FN and EC,
      also could lower CD44 and MMP-2 in cancer cells. CONCLUSION: ATI has the effects
      of antagonizing hepatocarcinoma cell adhesion and invasion, the mechanism may be
      related with the action of ATI in lowering CD44 and MMP-2 expression in cancer
      cells.

PMID- 15553830
TI  - [Effect of Astragalus polysaccharides and berberine on carbohydrate metabolism
      and cell differentiation in 3T3-L1 adipocytes].
AB  - OBJECTIVE: To compare the effects of Astragalus polysaccharides (AP) and
      berberine (BB) on the adipocyte's carbohydrate metabolism and cell
      differentiation, for assessing the possible mechanism of them in improving
      carbohydrate metabolism. METHODS: Adipocytes were treated with AP or BE, the 3H
      glucose up-take rate in them was investigated, those of differentiation phase
      were stained by oil red O to analyze the degree of cell differentiation by
      spectrophotography quantitatively. The adipocyte differentiation related
      expression of PPARgamma mRNA and C/EBPalpha mRNA were determined by RT-PCR.
      RESULTS: The 3H-glucose up-take rate in the AP group and BE group were 109.3% and
      182.7% of that in the blank control group respectively. AP obviously promoted the
      cell differentiation and up-regulated expression of PPARgamma mRNA, while BE
      suppressed the differentiation and expression of PPARgamma and C/EBPalpha mRNA
      distinctly, all showing significant difference as compared with that in the blank
      control (P<0.01). CONCLUSION: AP could promote glucose up-take, cell
      differentiation and PPARgamma mRNA expression, BB also promote glucose up-take,
      but suppress the cell differentiation, and inhibit expressions of PPARgamma and
      C/EBPalpha mRNA in 3T3-L1 adipocytes.

PMID- 15553831
TI  - [Exploration on the clinical effect and mechanism of Herba Rhodobryi Rosei in
      treating ischemic heart diseases].

PMID- 15553832
TI  - [Shengmai injection treating 53 neonates with anoxemic encephalopathy].

PMID- 15553833
TI  - [Some problems on standardization of clinical study on functional gastro
      intestinal diseases in Chinese medicine].

PMID- 15553834
TI  - [Recovery of endothelium, a new policy of integrative Chinese and Western
      medicine in prevention and treatment of post-PCI restenosis].

PMID- 15553835
TI  - [Study on the English translation of description of huangdi neijing suwen].

PMID- 15553836
TI  - [Progress of study on regulation of nuclear factor-kappaB activation with Chinese
      herbal medicine].

PMID- 15553837
TI  - [Progress on clinical study of Chinese medicine on malignant tumor complicated
      with depression].

PMID- 15553838
TI  - [The 5th national conference on neurology of integrative Chinese and Western
      medicine].

PMID- 15553839
TI  - [Capillary blood flow with dynamical change of tissue pressure caused by exterior
      force].
AB  - A hemodynamic model of capillary and tissue, in which tissue pressure changed
      with swing manipulation of Traditional Chinese Medical Massage (TCMM), is
      presented in this paper to explain the hemodynamic mechanism of swing
      manipulation. Blood flowed in capillary with low Reynolds number. Plasma exuded
      through capillary according to the Starling's Law. Tissue pressure changed
      linearly with the massage force measured. Blood apparent viscosity, plasma
      protein concentration and red cell's hematocrit were taken into account.
      Capillary flow rate, blood apparent viscosity, filtration rate and filtration
      fraction with dynamical change of tissue pressure were calculated numerically,
      and were compared with those in static tissue pressure condition. Results showed
      that, dynamical change of tissue pressure led to the increase of capillary flow
      rate and the decrease of blood apparent viscosity, which qualitatively explained
      the hemodynamic mechanism of "promoting blood circulation and removing blood
      stasis" in swing manipulation of TCMM.

PMID- 15553840
TI  - [Orthogonal test analysis of compressive strength of porous hydroxylapatite
      prepared by gel-casting process].
AB  - Porous hydroxylapatite (HA) has excellent osseous inductive ability. It has been
      prepared by gel-casting process, which is feasible and can make complex ceramic
      material. According to the result of orthogonal test based on the compressive
      strength, the order and the level of the factors, including monomer HA, initiator
      MBAM, catalyst APS and water, were dealt with. The effects of drying and
      sintering technique on the properties of porous hydroxylapatite were also
      researched. The results showed that the order of every factor in the gel-casting
      process is as follows, AM-APS, MBAM, H2O. Based on the determined level of each
      factor, the suitable slurry constituents and drying and sintering technologies
      were selected, and the porous hydroxylapatite with compressive strength of 6-7
      MPa was produced.

PMID- 15553841
TI  - [Experimental study of poly-DL-lactic acid membrane guided bone regeneration in
      rabbit radii bone defects].
AB  - This study was conducted to observe bone regeneration guided by poly-DL-latic
      acid (PDLLA) membrane in rabbit radii bone defects and to explore the mechanism
      of the membrane guided bone regeneration (MGBR). The animal models of bony and
      periosteous defects were established in both radii of 40 adult New Zealand white
      rabbits. The left defect as the experimental side was bridged with PDLLA membrane
      tube, the right side as the controlled side was untreated. The specimens were
      collected at 2, 4, 8 and 12 weeks postoperatively. General observation, X-ray,
      histological observation and biomechanical examination were applied to the repair
      of the models of MGBR in both groups. Two weeks after operation, with much new
      bony callus formed outside the tube at both fragments, the membrane tube covered
      with connective tissues was filled with haematoma and fibrous callus. Twelve
      weeks after operation, the PDLLA membrane became white and its tube shape was
      still maintained. However, new bone callus outside the tube almost completely
      disappeared, and inside the tubes all radii bone defects were successfully
      repaired with bony union. On the controlled sides, bone defects were filled with
      connective tissues 2 weeks postoperatively. And 12 weeks after operation, the
      typical nonunion that had been formed after bone marrow canals were sealed with
      cortical bone. On the experimental side, the strength of the newly formed bone at
      the 12th week was higher than that at the 8th week (P<0.05), whereas the
      biomechanical examination could not be done on the controlled side. Therefore,
      these findings suggested that the bone regeneration could be successfully guided
      by PDLLA membrane, and this MGBR technique might be generally used in the
      treatment of bone defects and nonunion.

PMID- 15553842
TI  - [Construct tissue-engineered bone by co-seeding marrow stromal cells and
      endothelial cells].
AB  - To identify the role of co-seeding marrow stromal cells (MSCs) and endothelial
      cells (ECs) onto biocomposite in constructing tissue-engineered bone for
      promoting osteogenesis and angiogenesis, we seeded rat marrow stromal cells
      (rMSCs) and human umbilical vein endothelial cells (hUVECs) onto poly (L-lactic
      acid)/beta-tricalcium phosphate (PLLA/beta-TCP) macroporous composite (the test
      group), and seeded rMSCs onto the same kind of composite (the control group). We
      implanted these biocomposites into the thighs of nude mice intramuscularly and
      sacrificed these mice at 1, 4, 8, 12, 16 weeks after implantation, respectively.
      Biocomposites were taken out and histomorphometry was performed. Image
      manipulation technology was used to calculate the percentages of new bone area
      and material area in the test group and control group. We found that the
      percentage of new bone area of test group increased faster than that of control
      group, the percentage of material of test group decreased faster than that of
      control group, and the growth of capillary network of test group was much better
      than that of control group. These results suggest that co-seeding MSCs and ECs
      onto scaffold for constructing tissue-engineered bone is beneficial to
      osteogenesis, to angiogenesis in the prosthesis, and to the degradation of
      scaffold, and it is of significance in the research of bone tissue engineering.

PMID- 15553843
TI  - [Study on relationship of biodegradable properties of PGLA film in vivo and in
      vitro].
AB  - This experimental study on the biodegradable properties of poly(glycolide-co
      lactide)[PGLA] film in vivo and in vitro was aimed to investigate the
      relationship between in vivo degradation process and in vitro degradation
      process. First, PGLA film was cut to 1 cm x 1 cm in size. It was put into
      artificial saliva and PBS solution respectively in vitro, and was implanted into
      subcutaneous tissue in Wistar rat in vivo. Then the mass loss rate was calculated
      every week not only for sample in vitro but also in vivo. The molecular weight
      was measured every two weeks. The results showed that the degradable speed of
      PGLA was faster in artificial saliva than in PBS solution. The change of
      molecular weight was earlier than that of mass loss rate. The degradable period
      in vitro was about 9-10 weeks. The degradable period in vivo was about 8 weeks.
      The rate of in vivo degradation was 1.33 times faster than that of in vitro. In
      conclusion, the degradation of PGLA in vitro was mainly a chemical degradation
      process achieved by hydrolysis of ester bond. The degradation of PGLA in vivo
      would be affected by stress and by biological factors, thus the degradation
      process was apparently faster in vivo, but both accorded with the degradation
      kinetics model of aliphatic polyester. There was some relationship of
      biodegradation between in vitro and in vivo.

PMID- 15553844
TI  - [Morphological analysis of acetabulum bony curved surface].
AB  - By using the reverse engineering (RE) technology, the mesh surface model of
      acetabulum was reconstructed by triangulation. Based on this kind of model, the
      local morphological analysis (LMA) and global morphological analysis (GMA) could
      be processed. The fitting minimal quadric surface method was applied to calculate
      the curvature of any point on the acetabulum bony surface, the local
      morphological character of its surface could be acquired, and its global surface
      character could be determined by GMA. The results showed that the acetabulum bony
      surface is elliptical surface, and its three eigenvalues (lambda1, lambda2,
      lambda3) relations on the three axes (x, y, z) are as follows: lambda1 is short
      than lambda2 and lambda3, lambda2 is close to lambda3.

PMID- 15553845
TI  - [The influence of Bazhen decoction on hematopoietic modulator in anaemic mice].
AB  - This study was designed to evaluate the effect of Bazhen decoction on bone marrow
      depression induced by cyclophosphamide (CY) in mice. An experimental model of
      mouse bone marrow injury was established through cyclophosphamide induced and the
      following phenomena were observed. The techniques of culture of hematopoietic
      progenitor cell and hematopoietic growth factor assay were used. Bazhen decoction
      could obviously promote the proliferation of bone marrow cells of anaemic mice.
      The culture media of spleen cell, macrophage, lung and skeletal muscle treated
      with Bazhen decoction had much stronger stimulating effects on hematopoietic
      cells. The bone marrow cells of the anaemic mice could yield TNF through Bazhen
      decoction treatment. It was suggested that Bazhen decoction is clinically a
      hopeful drug used to cure bone marrow depression and attenuate the side effects
      of CY.

PMID- 15553846
TI  - [The effects of anti-inflammatory on activation of nuclear factor-kappaB and
      expression of cell adhesion molecules in patients with ulcerative colitis].
AB  - The purpose of this study is to assess the effects of anti-inflammatory on
      activation of nuclear factor-kappaB and mRNA and protein expression of
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative
      colitis (UC). A total of 27 cases with UC were investigated. 15 cases received
      sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did
      not receive any medication related with UC. Normal mucosa from 9 colon cancer
      cases served as control. Ten pieces of intestinal mucosal biopsy specimens were
      obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were
      determined by reversal transcription-polymerase chain reaction (RT-PCR). The
      protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent
      assay (ELISA). NF-kappaB DNA binding activity was evaluated by electrophoretic
      mobility shift assay (EMSA). The results showed that NF-kappaB DNA binding
      activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased
      significantly in patients with UC, compared with normal control (P<0.05).
      Glucocorticoids and SASP markedly inhibited NF-kappaB activation and
      significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1
      (P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant
      positive correlation with the NF-kappaB DNA binding activity (r=0.8652 P<0.05,
      r=0.7902, P<0.05, respectively). We concluded that NF-kappaB is a major and
      essential factor in regulating the expression of adhesion molecules, it plays an
      important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC
      via inhibition of NF-kappaB activation and reduction of adhesion molecules
      expression.

PMID- 15553847
TI  - [A mathematical model of determining the knee joint injury].
AB  - A mathematical model of determining the injury of human knee joint was
      established by using structural dynamics method. The results showvered the
      corresponding shearing displacement and bending angle of the knee joint on the
      occasion of ligament avulsion, and the shearing force and bending moment which
      caused tibial condylar fractures under purest shearing and bending condition. The
      calculated results consisted with the experimental results greatly, suggesting
      that using mathematical method to determine the injury is feasible and this kind
      of method can do good to lots of subjects, such as pedestrian protection,
      athletic medicine and rehabilitation engineering.

PMID- 15553848
TI  - [Integrin beta1 mediates hepatocellular carcinoma cells adhesion & chemotaxis to
      type IV collagen].
AB  - A micropipette technique was adopted to investigate the effect of blockade of
      integrin betal on adhesion of hepatocellular carcinoma (HCC) cells onto type IV
      collagen (Col IV) coated surfaces and pseudopod protrusion of HCC cells in
      response to Col IV stimulation. Adhesion strength was expressed as an adhesion
      force, which was defined as the product of the cross sectional area and critical
      negative pressure needed to detach single cell away from the substrate.
      Chemotactic pseudopod protrusion of an HCC cell was evaluated using a dual
      pipette set-up, in which two pipettes filled with Col IV solution were positional
      in close contact with the same cell and pseudopod protrusion into each pipette
      was viewed dynamically and recorded with a tape recorder. The lengths of
      pseudopods were measured and plotted against time to obtain a pseudopod growth
      curve. The integrin beta1 subunit on the surfaces of HCC cells was analyzed by
      flow cytometry. The results showed that the adhesion forces for HCC cells
      adhering on 5 microg/ml Col IV coated surfaces were 932 +/- 134 (x 10(-10) N, n =
      60). Upon treatment of HCC cells with Anti-CD29 in a protein concentration of 5
      microg/ml and 10 microg/ml, the value decreased significantly to 449 +/- 119 (x
      10(-10) N, n = 60) and 220 +/- 78 (x 10(-10) N, n = 55), respectively. In dual
      pipette chemotaxis experiment, when the two pipettes were filled with Col IV in
      an identical concentration of 600 microg/ml, pseudopods extended from the HCC
      cell into each of the pipettes nearly symmetrically, i.e., with nearly identical
      maximum pseudopod length and similar pseudopod growth curves. Upon addition of
      Anti-CD29 to one of the pipettes in a protein concentration of 20 microg/ml,
      pseudopod protrusion was blocked nearly completely while protrusion into the
      opposite pipette became more evidently, with larger maximum length. Expression of
      integrin beta1 was up to 95.78% to cells chosen in the experiment. These results
      suggested that integrin beta1 subunit was important constituent receptor subunit
      for mediating HCC cell adhesion and chemotactic pseudopod protrusion to Col IV.

PMID- 15553849
TI  - [Isolation and cultivation of mouse bone marrow mesenchymal stem cells].
AB  - To establish the best condition of isolation and cultivation of mouse bone marrow
      mesenchymal stem cells (BMSCs) in vitro, we isolated BMSCs from BALB/C mouse
      using density gradient centrifugation and adherent selecting. The effects of
      different centrifuge power, adherent time, serum concentration and cell density
      on the isolation and cultivation of BMSCs were investigated. The best isolating
      condition is: 500g x 30min, 24 hours adhering. The best cell density is 12-20 x
      10(5)/ml of primary cells and 6.4-25.6 x 10(4)/ml of secondary cells. The best
      serum concentration is 10%. More than 90% of subcultured cells were adhesive in 8
      hours. Thus we have established a cell biological method of isolation and
      cultivation of BMSCs.

PMID- 15553850
TI  - [Study on eliminating self-dithering interference of the system for non-contact
      detecting life parameters based on an adaptive algorithm].
AB  - The non-contact life parameters detecting systems can detect many important life
      parameters such as heartbeat and breathing at certain distance. In practice, the
      self-dithering interference of the system is produced by some factors; it makes
      the signal-to-noise ratio (SNR) of the recorded signal lower. This paper is
      discussed an adaptive technology based on a variable step-size LMS algorithm,
      which is used to eliminate the self-dithering interference of the system and
      hence to raise the SNR of the detecting signal. A method to obtain the reference
      signal by vibration sensor is brought forward and the optimum parameters settings
      are discussed. The results show that the reference signal is an integral part of
      output signal of the vibration sensor and has a relationship with the setting
      direction of the sensor. The conclusion is that the method is effective and
      feasible; also the algorithm is well convergent.

PMID- 15553851
TI  - [Frequency-domain analysis methods for single ion channel currents].
AB  - The frequency domain of single channel currents is analyzed by the power
      distribution function (PDF) constructed by the discrete wavelet transform (DWT)
      and power spectral density (PSD). The result shows that the power distribution
      function based on DWT is an effective frequency-domain analysis method for single
      channel currents.

PMID- 15553852
TI  - [Digital model of human lower extremity musculature based on CT & MRI].
AB  - A new method to reconstruct comparatively complete muscle model of human lower
      limb from CT and MRI data is presented. Topological structure of more than
      fourteen muscles is built and the coordinates of origin and insertion points are
      given. Based on this model, straight-line model and centroid-line muscle model
      are acquired. Muscle force prediction is discussed according to the model
      reconstructed, and a multi-objective optimization method is put forward for
      evaluating muscle forces of human lower extremity.

PMID- 15553853
TI  - [An improved back-projection algorithm of dynamic electrical impedance
      tomography].
AB  - In this paper, an improved back-projection algorithm of dynamic electrical
      impedance tomography (EIT) was described. The improved back-projection algorithm
      modified the computing method of back-projection matrix B. Dynamic reconstruction
      image was obtained by the improved algorithm, and it was compared to the image
      obtained by the traditional method of equi-potential back-projection. The results
      showed that the improved algorithm of equi-potential back-projection could locate
      the object's position in the field with higher precision, and its speed was very
      fast. It also could improve the resolution of the reconstructed image in some
      extent.

PMID- 15553854
TI  - [Computer simulation of high frame rate ultrasonic imaging system based on the
      angular spectrum concept].
AB  - A high frame rate (HFR) ultrasonic imaging method developed by Jianyu Lu has been
      attracting attention in the related imaging area. Because a special weighting on
      the received signal is needed to implement this method, the imaging system is
      complicated. This paper presents a new kind of theroetical analysis for the HFR
      imaging system in view of the angular spectrum concept. Based on the study, the
      special weighting process can be replaced by Fourier transform. Computer
      simulation demonstrates the correctness of the analysis. It shows that the
      constructed images by the new method have the same high quality as those obtained
      by using the original HFR method while the system implementation is greatly
      simplified.

PMID- 15553855
TI  - [Dynamical analysis of the nonlinearity in the model of acute myocardial
      ischemia].
AB  - By analyzing the electrocardiosignals, many scholars have found remarkable and
      outstanding dynamic characteristics in both normal hearts and sick hearts. Based
      on those findings, a model of acute myocardial ischemia of six rabbits is
      designed by us and is presented here. The electrocardiogram (ECG) signals of
      different time series are calculated, and the figures of correlation dimensions
      time and the maximum Lyapunov exponents-time are given. The results show that the
      existence of myocardial ischemia will bring the decline of the value of maximum
      Lyapunov exponents and correlation dimensions, after the figures being analyzed
      with electrophysiological and anatomical knowledge. The maximum Lyapunov
      exponents of ECG demonstrate the chaotic quality of the system and the
      correlation dimension of ECG demonstrates the complexity of the system, and there
      is no explicit relation between them. Correlation dimensions of ECG signals might
      be more influenced by partial heart system, compared with the maximum Lyapunov
      exponents of ECG signals.

PMID- 15553856
TI  - [Image processing method based on prime number factor layer].
AB  - In sport games, since the human body movement data are mainly drawn from the
      sports field with the hues or even interruptions of commercial environment, some
      difficulties must be surmounted in order to analyze the images. It is obviously
      not enough just to use the method of grey-image treatment. We have applied the
      characteristics of the prime number function to the human body movement images
      and thus introduce a new method of image processing in this article. When trying
      to deal with certain moving images, we can get a better result.

PMID- 15553857
TI  - [An analysis system of physical training workload based on Polar Sports Tester].
AB  - The polar sports tester made in Finland as one of the most widespread instruments
      in physical training is of importance for sports training. In this paper, we have
      developed a set of system for analysis of physical training workload using the
      measured data of the Polar Sports Tester, and have established a set of analysis
      indices and reports of the physical training workload, including five categories
      and 127 quantitative indices. It can reflect the distribution of physical
      workload and provide a series of parameters for coaches to direct scientific
      training and raise sport level.

PMID- 15553858
TI  - [Research on the R-PS integration technique of digital radiology].
AB  - In this paper, the R-PS integration technique of the digital radiology is
      discussed. By the integration of the RIS and PACS, all data and information of
      each system and each medical image equipment in R-PS can be exchanged according
      to DICOM3.0, and seamless linkage can be realized by module interfaces. R-PS has
      many advantages such as share, safety, compatibility, practicability and
      feasibility. Standardization of communication interface, modularization of
      application and resource share of medical information can be realized by this
      technique.

PMID- 15553859
TI  - [A study of ECG combination detection algorithm based on wavelet transform and
      morphological method].
AB  - In order to deal with the disadvantages in ECG waveform detection by wavelet harr
      transform at level 3, we put forward a new set of algorithm which combines
      wavelet transform (WT) and morphological peak and valley detection. The
      combination algorithm can make up the limitation in detecting ECG swing by WT and
      improve the accuracy of ECG waveform detection effectively.

PMID- 15553860
TI  - [Study on thermo-sensitive intelligent targeting type drug carriers (I) porous
      membranes with grafted thermo-sensitive gates].
AB  - Thermo-responsive intelligent membranes with linear grafted poly(N
      isopropylacrylamide) (PNIPAM) gates on the inner pore surface were prepared, and
      experiments were carried out on the thermo-responsive gating characteristics.
      Plasma-graft pore-filling polymerization was used to graft PNIPAM into the pore
      of the porous flat membranes. The experimental results showed that PNIPAM-grafted
      PVDF (PNIPAM-g-PVDF) membranes were featured with thermo-responsiveness due to
      the thermo-responsive swollen-shrunken property of PNIPAM chains grafted on the
      inner pore surface of the membrane. At temperatures below the lower critical
      solution temperature (LCST), the linear grafted PNIPAM chains on the inner pore
      surface were in the swollen state, and the pores in the membrane were closed; in
      contrast, the grafted PNIPAM chains were in the shrunken state at temperatures
      above the LCST, and therefore the pores in the membrane were open. The LCST of
      the thermo-sensitive gates could be adjusted by adding acrylamide (AAM) in the N
      isopropylacrylamide (NIPAM) monomer solution, the LCST of the poly(NIPAM-co-AAM)
      gates increased simply with the increase of the AAM fraction.

PMID- 15553861
TI  - [Purification and partial characterization of hepatitis C virus (HCV) non
      structural protein 5A (NS5A) expressed in Escherichia coli].
AB  - It has been suggested that non-structural protein 5A (NS5A) of hepatitis C virus
      (HCV) may have a regulatory role similar to other RNA viruses in RNA replication.
      In order to investigate the replication function of NS5A, we tried to purify
      recombinant His(6) tagged NS5A expressed in Escherichia coli by a denature
      renaturing method. The native lysis buffer was used to remove most of the soluble
      non-specific proteins. His-NS5A protein was solublized with the denaturing lysis
      buffer containing 8 mol/L Urea, and then bound to Ni2+ -NTA resin. The protein
      bound resin was successively washed with buffer containing reducing
      concentrations of Urea in the presence of NaCl and DTT to renature the protein.
      The renatured His-NS5A protein was eluted from the resin and it was capable of
      interacting with glutathione S-transferase fused form NS5Bt (GST-NS5Bt). The
      purified His-NS5A exhibited an inhibitory effect on RNA-dependent RNA Polymerase
      (RdRP) activity of GST-NS5Bt in vitro. Conclusively, in this study, we have
      established a purification method of bacterial recombinant HCV NS5A, and the
      results support the notion that NS5A may involve in the regulation of HCV
      replication through direct interaction with NS5B.

PMID- 15553862
TI  - [Cellular compatibility of small intestinal submucosa in vitro].
AB  - This study was aimed to evaluate the cellular compatibility of the small
      intestinal submucosal(e) (SIS). Prepared by use of pig jejunum. SIS were
      cocultured with human embryonic periosteal osteoblasts (HEPOB), human embryonic
      skin fibroblasts (HESFB) and rabbit renal vascular endothelial cells (RRVEC)
      respectively. The cell growth, attachment, cell cycle, cell apoptosis rate were
      detected to evaluate the cellular compatibility of SIS. The three kinds of cells
      attached onto SIS and grew well. SIS accelerated the growth of RRVEC. No effects
      of SIS were detected on cell cycle and cell apoptosis rate in the three kinds of
      cells. SIS has good cellular compatibility without cytotoxicity. The porous
      structure of SIS is suited for the growth of HEPOB, HESFB and RRVEC in three
      dimensions in the scaffold. SIS is a good bio-derived material of tissue
      engineering.

PMID- 15553863
TI  - [Preparation of recombinant human insulin--study of downstream process].
AB  - This study was intended to establish a method of preparation of recombinant human
      insulin, with (His)6-Arg-Arg-human proinsulin (RRhPI) expressed by Escherichia
      coli. After DEAE-Sepharose Fast Flow ion-exchange chromatography, Sephadex G-25
      chromatography and refolding, enzyme cleavage and Superdex 75 size exclusion
      chromatography,the RRhPI expressed by Escherichia coli in inclusion body form was
      converted to human insulin. The obtained recombinant human insulin was analyzed
      by SDS-PAGE, HPLC, amino acid composition analysis and bioidentity test (mouse
      convulsion test). The results indicate that our obtained preparation is highly
      purified, active recombinant human insulin.

PMID- 15553864
TI  - [Clinical study on blood salvage technique in spine orthopaedic operation].
AB  - To evaluate the application of blood salvage techmque in spine orthopaedic
      operation. 26 cases of spine orthopaedic operations were divided into two groups.
      Group A received homologous blood transfusion. Group B received intraoperative
      blood salvage by cell saver in spine orthopaedic operations. No complications of
      transfusion and dysfunciton were found in all pateints. The results showed that
      blood salvage technique can decrease effectively the need of homologous blood
      transfusion in spine orthopaedic operation and can be used safely in clinical
      practice.

PMID- 15553865
TI  - [Molecular cloning and analysis of a monocot mannose-binding agglutinin from
      Zephyranthes grandiflora (family Amaryllidaceae)].
AB  - The monocot mannose-binding lectin can inhibit HIV from infecting the target
      cells. The total RNA of Zephyranthes grandiflora was extracted and reversely
      transcribed into cDNA. Degenerate primers were designed based on the conserved
      regions of other monocot mannose-binding agglutinins by homology alignment. The
      694bp full-length cDNA of Zephyranthes grandiflora agglutinin (ZGA) was cloned by
      RT-PCR, 3' and 5' RACE (rapid amplification of cDNA ends). The start codon and
      stop codon of ZGA were at 37-39bp and 529-531bp respectively. The NCBI Blast
      analysis result showed that ZGA gene encoded a protein precursor with signal
      peptide, mature protein and C-terminal cleavage sequence. The mature ZGA protein
      contained 106 amino acids residues and its molecular weight was 11.6KD. The
      percentages of identity of the deduced mature ZGA protein with those of Galanthus
      nivalis agglutinin, Narcissus hybrid cultivar agglutinin, Lycoris radiate
      agglutinin and Clivia miniata agglutinin were 71.8%, 81%, 81.8% and 84.5%,
      respectively. Blocks analysis revealed that ZGA had three functional domains and
      three mannose-binding boxes (QDNY).

PMID- 15553866
TI  - [Development of multi-channels cardiac electrophysiological polygraph with
      LabVIEW as software platform and its clinical application].
AB  - Polygraph has become a necessary instrument in interventional cardiology and
      fundamental research of medicine up to the present. In this study, a LabView
      development system (DS) (developed by NI in U.S.) used as software platform, a
      DAQ data acquisition module and universal computer used as hardware platform,
      were creatively coupled with our self-made low noise multi-channels preamplifier
      to develop Multi-channels electrocardiograph. The device possessed the functions
      such as real time display of physiological process, digit highpass and lowpass,
      50Hz filtered and gain adjustment, instant storing, random playback and printing,
      and process control stimulation. Besides, it was small-sized, economically
      practical and easy to operate. It could advance the spread of cardiac
      intervention treatment in hospitals.

PMID- 15553867
TI  - [Experimental research on OGTT for non-invasive blood glucose detection through
      near-infrared spectroscopy ranging from 1100 nm to 1700 nm].
AB  - For non-invasive blood glucose detection through near-infrared spectroscopy, it
      is very important to ensure the data quantity and reliability of calibration
      model. In this paper, the method of sampling blood by tubing pump in OGTT (Oral
      Glucose Tolerance Test) is used to get reliable and adequate reference data of
      blood glucose concentration for calibration model, and the non-invasive blood
      detection system based on the AOTF (Acousto-Optic Tunable Filter) ranging from
      1100 nm to 1700 nm is designed. 3 experiments were performed by the above system
      and method. The results showed that based on the PLS (Partial Least Square)
      calibration models constructed by analyzing all individual experimental data, the
      correlation coefficients were 0.986, 0.971 and 0.985, respectively, and the RMSEP
      (Root Mean Square Error of Prediction) estimated by Full Cross Validation were
      0.550 mmol/l, 0.456 mmol/l and 0.520 mmol/l; respectively. The results also
      showed that the prediction error of the model decreased when the number of
      effective model data increased.

PMID- 15553868
TI  - [A study on new computer-aided modeling method of hip joint].
AB  - The main reason of invalidation of prosthetic hip joint is the prostheses
      flexibility and shift, dislocation and disjunction. Promoting the long time
      stability of the prostheses is the key of improving the long term hip joint
      replacement effect. Former research work was focused on the upper segment of
      femur, and assumed the acetabulum cup to be a spheric concave, and the external
      form of acetabulum prostheses was basically semi spheric. This paper presents a
      method of acquiring the point data on the surface of the hip bone using the
      reverse engineering technology. By analyzing the acetabulum surface fitting error
      we use rotating elliptical surface to fit the acetabulum surface, together with
      the optimal technique to build up the CAD model of acetabulum surface. We compare
      the fitting error between the sphere fitting and rotating elliptical surface
      fitting and get the result that the rotating elliptical surface fitting error is
      smaller than the sphere fitting error, and the rotating elliptical surface can
      describe the shape of the acetabulum better.

PMID- 15553869
TI  - [Heart sound recognition algorithm based on mathematical morphology].
AB  - In this paper, a new method was put forward for automatic recognition of the
      first heart sounds (S1) and the second heart sounds (S2). After the original
      heart sound signal was preprocessed, the heart sound envelope was extracted by
      using the mathematical morphology. Then on the heart sound envelope, S1 and S2
      were recognized. Eighty heart sound samples collected were used for testing the
      algorithm. The accuracy of recognition was 86%, and was 100% for the normal heart
      sound. The result showed that the algorithm proposed in this paper had high
      performance, which could be used as a basis for further analysis of heart sound.

PMID- 15553870
TI  - [A primary investigation on the dynamic changes of correlation dimension of
      animal's ECG signals].
AB  - The dynamic changes of synchronous 12-lead ECG signal's correlation dimension
      (D2) of an anesthetized rabbit were investigated primarily under three different
      pathologic conditions. The results showed that the D2 derived from different lead
      signals was not a constant whether the rabbit was in normal state or in emergent
      myocardial infarction condition, it demonstrated distribution characteristic.
      Compared with the same lead signal, D2 of limb lead almost kept constant, D2 of
      chest lead got higher when the sphere of emergent ischemia extended larger. D2
      showed the potential application in the diagnosis of coronary heart disease.

PMID- 15553871
TI  - [The data management of 3D FE model reconstruction based on medical Images and
      the modeling for T10-T12 thoracic vertebrae].
AB  - Setting up the 3D finite element (FE) model on the basis of medical images is a
      necessary method of biomechanical analysis. The pretreatment, including data
      processing of images and mesh generation, becomes the bottleneck of FE analysis,
      and this is especially the case of the modeling for thoracic vertebrae, because
      the shapes and data are complicated. In this paper, on the basis of the data for
      building a 3D FE model of thoracic vertebrae, we present some structures and
      types of data which are essential for the reconstruction of CT medical image,
      analyze some methods for obtaining and processing the data from images, and then
      advance a theory for data management based on mesh generation by block with the
      software MSC. Marc. A 3D-FE Model of T10-T12 thoracic vertebrae is set up, which
      keeps the configuration of the true one, and satisfies the requirements of
      biomechanical analysis. We focus affention on the data obtainment and management
      during medical image processing and FE modeling, all of which are very important
      for the biomechanical analysis. It is helpful and instructive to reconstruct some
      similar tissues of human body on the basis of the medical images from CT, MRI,
      etc.

PMID- 15553872
TI  - [Experimental study on the fabrication of bioactive membrane for inducing bone
      regeneration].
AB  - The aim of this study was to develop a bioactive membrane for inducing bone
      regeneration. The membrane was composed of polylactic acid, collagen, recombinant
      human bone morphogenetic protein-2 (rhBMP-2). The PLA + collagen + rhBMP-2
      membrane was fabricated by solvent-casting and cool-drying. The mechanic
      properties of this compound membrane were tested. The two surfaces of membrane
      were observed by SEM. Degradability of PLA was evaluated by SEM observation and
      molecular weight measure in vitro and in vivo. The compound membranes were
      implanted in rabbit muscles. The samples were obtained when animals were
      sacrificed at different periods: 2 weeks, 1, 2, 3, 6 months after surgery. The
      biodegradability and biocompatibility of the membrane were evaluated. The
      heterotopic bone inducing activity of BMP was identified. The results indicated
      that the strength at extension to failure of the compound membrane was 36.4MPa at
      2.3% strain. The compound membrane was found bearing active factor on its coarse
      side, which can induce bone regeneration. After implantation in vivo, the
      membrane maintained the structure for three months and degraded in 6 months.
      Based on histological analysis, there was no obvious inflammation. Heterotopic
      bone was induced. We could conclude that the PLA + collagen + rhBMP-2 membrane is
      an absorbable compound membrane that possesses good biocompatibility, adequate
      mechanic properties and excellent property of bone induction. It could be applied
      as an ideal membrane for inducing bone regeneration.

PMID- 15553873
TI  - [RNA interference in functional genomics and medical research].
AB  - RNA interference (RNAi) is a post-transcriptional gene silencing process by
      targeting mRNA for degradation in a sequence-specific manner. This powerful
      platform has enormous potential in functional genomics and medical research. As a
      tool to knock out expression of specific genes in a variety of organisms, RNAi
      was used to investigate gene function in a high throughput fashion. Highly
      conserved in evolution RNAi appears to have evolved as a cellular defense
      mechanism in plants and animals to suppress viral infection, transposon jumping
      and endogenous aberrant genes. Exploiting the natural mechanism, the researchers
      can shut down disease-causing genes and develop novel therapeutics against
      infection, tumor and other disease.

PMID- 15553874
TI  - [The advance in researches for biomedical intelligent polymer materials].
AB  - The properties of biomedical intelligent polymer materials can be changed
      obviously when there is a little physical or chemical change in external
      condition. They are in the forms of solids, solutions and polymers on the surface
      of carrier, including aqueous solution of hydrophilic polymers, cross-linking
      hydrophilic polymers (i.e. hydrogels) and the polymers on the surface of carrier.
      In this paper are reviewed the progress in researches and the application of
      biomedical intelligent polymer materials.

PMID- 15553875
TI  - [The cryopreservation technology in research and development of tissue engineered
      products].
AB  - In this brief review, some key issues related to cryopreservation of seeding
      cells, scaffolds, and engineered tissues are outlined. The importance of
      cryopreservation technology to the research and development of tissue engineered
      products is demonstrated. The biological or biochemical reaction rate must be
      reduced or completely shut off in order to preserve the tissue engineered
      products for a long period of time. Cryopreservation may be one of the possible
      approaches to the fulfillment of this requirement. Seeding cells are stored at
      low temperature. Tissue engineered scaffold products are usually lyophilized.
      Engineered tissues are preserved by vitreous cryopreservation technology.

PMID- 15553876
TI  - [In-vitro evaluation of haemocompatibility of biomaterials].
AB  - In-vitro test is usually conducted as a preliminary screening test in the
      evaluation of the haemocompatibility of biomaterials for its short-term
      consuming, convenience and less expense. The selection of appropriate model for
      blood-biomaterial interaction, the choice of sensitive and specific parameters,
      and the minimization of additional blood activation are most important in the in
      vitro test. In addition, the time and the style of blood-biomaterial interaction,
      the choice of sensitive and specific parameters, and the minimization of
      additional blood activation are most important in the in-vitro test. In addition,
      the time and the style of blood-biomaterial interaction, the selection of primary
      reference materials and the shear rate should be considered. In recent years,
      though great progress has been made in the in-vitro evaluation of
      haemocompatibility of biomaterials, all these influencing factor should be
      standardized for more effective evaluation of the haemocompatibility of
      biomaterials.

PMID- 15553877
TI  - [Microbial corrosion of dental alloy].
AB  - There is a very complicated electrolytical environment in oral cavity with plenty
      of microorganisms existing there. Various forms of corrosion would develop when
      metallic prosthesis functions in mouth. One important corrosive form is microbial
      corrosion. The metabolic products, including organic acid and inorganic acid,
      will affect the pH of the surface or interface of metallic prosthesis and make a
      change in composition of the medium, thus influencing the electron-chemical
      reaction and promoting the development of corrosion. The problem of develpoment
      of microbial corrosion on dental alloy in the oral environment lies in the
      primary condition that the bacteria adhere to the surface of alloy and form a
      relatively independent environment that promotes corrosion.

PMID- 15553878
TI  - [Pathological development of researches on intervertebral disc degeneration].
AB  - This article reviews the literature about the etiology and pathology of
      intervertebral disc degeneration. The degeneration of intervertebral disc is
      associated with certain biomechanical factor. Stress can directly lead to the
      rupture of intervertebral disc and, more importantly, change its biological
      properties. And then, it can trigger the process of degeneration via inflammatory
      mechanism which may include autoimmunity.

PMID- 15553879
TI  - [The application and advancement of rapid prototyping technology in bone tissue
      engineering].
AB  - In bone tissue engineering, a highly porous artificial extracellular matrix or
      scaffold is essential to the attachment, proliferation and differentiation of
      bone cells (osteoblast, osteoclast and osteocytes) and the formation of bone
      tissue. However, conventional scaffold materials for bone tissue engineering
      proved less valuable for actual applications because they lack mechanical
      strength, interconnected channel network, and controllable porosity or channel
      size. Therefore,to explore the ideal scaffold materials is one of the popular
      studies on current bone tissue engineering. In this paper, we review, the
      application and advancement of a newly-developed technology generally known as
      rapid prototyping (RP) techniques in bone tissue engineering.

PMID- 15553881
TI  - International Nurses' Day: 12th May 2004. Nurses working with the poor; against
      poverty.

PMID- 15553880
TI  - [Therapy for Graves' ophthalmopathy].
AB  - Graves' ophthalmopathy (GO) is also called thyroid-related eye disease,
      infiltrative ophthalmopathy, which is related with the autoimmunity of thyroid,
      especially hyperthyroidism. Its morbidity ragnes from five percent to ten percent
      of hyperthyroidism, and the morbidity of male patients is higher than that of the
      female patients. The treatment of severe GO is a difficult task for doctors. The
      therapeutic effect is not always satisfactory. In order to solve this knotty
      problem, researchers have been devoting themselves to the development of new
      therapeutic methods. Here, the development of the therapies for GO is introduced,
      and the trends of treatments are prospected.

PMID- 15553882
TI  - Effectiveness of teaching on episiotomy & perineal care among primipara women of
      selected hospitals in Karnataka.

PMID- 15553883
TI  - Nurses' role in the management and prevention of pressure ulcers--a study.

PMID- 15553884
TI  - Get involved!

PMID- 15553885
TI  - Power and paste system premiers.

PMID- 15553886
TI  - Gingival recessions caused by lip piercing: case report.
AB  - Fear of losing the teeth is common among patients presenting with gingival
      recession. This report describes a case in which unusual gingival recessions were
      caused by lip piercing. Periodontal treatment involved removal of the causative
      agent, hygiene instruction, scaling and root planing, and coverage of the root
      with a subepithelial connective tissue graft. The therapeutic measures applied in
      this case yielded satisfactory root coverage, an increase in the width of the
      keratinized gingiva, improvement in hygiene status and absence of dental
      hypersensitivity.

PMID- 15553887
TI  - News from the front.

PMID- 15553889
TI  - Building an empire, one implant at a time.

PMID- 15553888
TI  - My day as a "solo" practitioner.

PMID- 15553890
TI  - Dentistry as canary?

PMID- 15553891
TI  - World Health Day Theme 2004 road safety is no accident.

PMID- 15553892
TI  - Workshop. 'Nursing management of patients in critical care areas'--a report.

PMID- 15553893
TI  - The effect of information booklet provided to caregivers of patients undergoing
      haemodialysis on knowledge of home care management.

PMID- 15553894
TI  - Motivating nursing personnel.

PMID- 15553895
TI  - "Study to assess knowledge of legal responsibilities in patient care among
      nursing graduates".

PMID- 15553896
TI  - [Radiology 3/Solution. Dry cough. Sarcoidosis (Boeck's disease), stage 2].

PMID- 15553897
TI  - [Ultrasound for renal colic].
AB  - Nowadays the Spiral-CT-scan is stressed as the diagnostic "gold-standard" in the
      management of kidney-colics. Our findings suggest a very good sensitivity (98%)
      and specificity of diagnostic ultrasound (items:Hydrourether, RI > 0.05) in
      combination with hematuria in an ambulatory setting. Our data are referred to 70
      ambulatory patients examined with the hypothetical diagnosis of kidney-colic in a
      general medicine surgery between 1996-2003. Diagnostic ultrasound is a reliable
      tool in the management of kidney-colics in ambulatory medicine. Its cost-saving
      character and the lack of X-rays-exposure should be taken into account in
      choosing the appropriate method in judging abdominal pains possibly related to
      kidney-colics.

PMID- 15553898
TI  - [The importance of a careful examination of all persons in close contact with
      newly diagnosed infectious tuberculosis].
AB  - The diagnosis of infectious pulmonary tuberculosis was made in a 53-year-old
      Macedonian man. A careful examination of all persons in close contact with him
      according to the guidelines of the Swiss respiratory society was performed.
      Pulmonary tuberculosis was diagnosed in his 22-year-old son, in his 20-year-old
      daughter and in his 3-year-old granddaughter. Seven persons had isoniazid
      preventive treatment for latent tuberculosis. These data shows very clearly that
      a careful examination of all persons in close contact with contagious
      tuberculosis is very important.

PMID- 15553899
TI  - [An unusual case of hepatic abscess].
AB  - Right upper quadrant pain with chronic malaise and fever can be the clinical
      manifestation of a hepatic infection. An uncommon cause for the disease is
      hepatic actinomycosis. Actinomycosis was common in the preantibiotic era but is
      less frequent nowadays; consequently its timely recognition has become more
      difficult. The clinical and radiological findings often resemble other
      inflammatory and neoplastic lesions. We report a case of a mixed anaerobic liver
      abscess including fusobacteria and actinomycetes, without apparent predisposing
      factor. The diagnosis was obtained by CT-guided percutaneous aspiration of the
      hepatic mass, where microscopy revealed the presence of fusiform gramnegative
      bacteria and gram-positive branching filamentous rods consistent with Actinomyces
      species. The latter did not grow in culture, while the gram negatives were
      identified as fusobacterium nucleatum. The diagnosis of actinomycosis of the
      liver is confirmed in only a minority of cases by culture. The disease is usually
      treated with an extended course of antibiotics. Penicillin is the preferred
      choice.

PMID- 15553900
TI  - [Acute hepatitis after use of nimesulide: drug-induced or is there something
      more? Mononucleosis].

PMID- 15553901
TI  - Simple method for large-scale isolation and purification of gangliosides by non
      ionic adsorption chromatography.
AB  - A type of non-ionic adsorption resin, X-5, was used in the isolation and
      purification of brain gangliosides. Hydrolysis with base treatment was carried
      out for the purpose of eliminating contaminants. The major advantages of the new
      procedure, compared to conventional methods, were the shorter separation time,
      higher loading capacity (80 micromol LBSA per gram resin), and recovery (98%) of
      separated ganglioside fractions with little solvent. It is a practical way for
      large-scale isolation and purification of gangliosides.

PMID- 15553902
TI  - Use of SP-Sephadexto fractionate and obtain semi-pure preparation from whole
      pituitaries of Indian water buffaloes (Bubalus bubalis).
AB  - Different charge isoforms of native Luteinizing hormone (LH) (dimeric form) Ve/Vo
      = 1.49 can be fractionated on SP-Sephadex into four different charge isoforms
      (LHUB, LH25, LH50, and LH100) by stepwise elution using different molarities of
      Na2HPO4. LHUB was found to be difficult to purify, whereas LH50 and LH100 were
      found to be pure and highly immunoreactive against anti-bLHbeta serum as
      indicated by the results obtained from direct binding ELISA and Western blot
      analysis. SDS-PAGE of LH50 and LH100 showed two bands corresponding to the two
      subunits of LH. LH25 can be purified to homogeneity by rechromatography on S-300.
      Purification of buLH as a highly immunoreactive preparation has also been
      described using SP-Sephadex. This LH preparation (SP25B), which was obtained
      after slight modification in the pre-existing protocol, has been found to be
      highly immunoreactive against anti-bLHbeta serum in direct binding ELISA. Being a
      very simple and reproducible method, it can be used to obtain pure LH
      preparation, as a reference material, in a short period of time for various
      immunoassays and bioassays.

PMID- 15553903
TI  - Simultaneous isolation of prolactin and growth hormone from "discarded acid
      pellet" obtained from buffalo pituitaries.
AB  - An acid pellet, obtained as a side fraction from a conventional gonadotropin
      purification pathway, has been found to contain the bulk of the pituitary
      lactogenic hormones (growth hormone or GH and prolactin or PRL). This discarded
      side fraction has been utilized to obtain buffalo lactogenic hormones (buGH and
      buPRL), simultaneously, and in bulk. The immunoreactivities of the purified semi
      pure buffalo GH and PRL (APECS and APP-I, respectively) preparations were
      compared by direct binding ELISA with semi-pure standard buGH and PRL (ECS and EP
      I, respectively) and were found to be as pure as standard semi-pure buGH and
      buPRL. When checked by direct binding ELISA using buGH and buPRL antisera, it was
      observed that APECS and APP-I were not cross-immunoreactive. SDS-PAGE and western
      blot analysis of APECS and APP-I showed major bands located at the same positions
      as in the case of standard semi-pure preparations (20 kDa for APECS and 23 kDa
      for APP-I). The semi-purified buGH and buPRL (APECS and APP-I) were converted to
      a highly purified preparation by chromatographing them via Sephacryl S-200 gel
      filtration chromatography.

PMID- 15553904
TI  - Chromatographic behavior of Bothrops erythromelas phospholipase and other venom
      constituents on Superdex 75.
AB  - In a chromatographic method modification intended to preserve protease activity
      in Bothrops erythromelas venom, 2 mM CaCl2 was added to the gel filtration buffer
      [50mM Tris/HCl/150mM NaCl (pH 8.0)], in lieu of an equimolar portion of NaCl.
      This minor compositional change induced significant differences in the venom
      elution profile on Superdex 200. For this reason, the influence of buffer
      composition on chromatographic behavior was investigated using an analytical
      Superdex 75 HR 10/30 column. Phospholipase (PLA) was used as a marker because
      Naja atra PLA had previously been observed to interact hydrophobically with this
      resin. PLA elution volumes generally increased as buffer pH decreased. Addition
      of 20% acetonitrile to the Tris buffer with CaCl2, reduced hydrophobic
      interaction of the PLA so significantly that its elution was non-overlapping in
      the two buffers. Other venom constituents, including bradykinin-potentiating
      peptides and probable hemorrhagic metalloproteases, were similarly affected.
      Buffer calcium, bound by vicinal dextran hydroxyl groups, appears to retard
      elution of this acidic PLA.

PMID- 15553905
TI  - Polyvinyl alcohol--trypsin as a catalyst for amino acid ester synthesis in
      organic media.
AB  - The bovine trypsin-catalyzed synthesis of N-alpha-benzoyl-DL-arginine esters from
      N-benzoyl-DL-arginine were studied in various organic solvents. Trypsin was
      immobilized to polyvinyl alcohol (PVA) by adsorption from its aqueous solutions.
      Immobilized enzyme showed higher catalytic activities than free enzyme for amino
      acid esterification in ethanol. The yield of ester is strongly dependent upon the
      PVA/trypsin ratio and water content in the reaction medium. The rate and
      equilibrium constant of the ester formation reaction are also dependent on water
      content.

PMID- 15553906
TI  - A novel method for simultaneous purification of albumin and immunoglobulin G.
AB  - A novel method was developed to obtain both highly purified bovine serum albumin
      (BSA) and immunoglobulin G (IgG), at the same time, on a pilot scale. Heat
      isopropyl alcohol was used to denature and precipitate the other plasma proteins,
      except for BSA and IgG; then, CM-Trisacryl was applied to further purify and
      isolate BSA and IgG. The new procedure produced highly purified BSA and IgG, 98%
      and 96.8%, respectively, and yielded ideal output, 2.18% and 0.54%, from starting
      plasma, respectively. The new technique is a rapid and is an available pilot
      process to prepare the plasma fractions devoid of cellular components.

PMID- 15553907
TI  - Some biochemical properties of polyphenol oxidase from celery.
AB  - Polyphenol oxidase (PPO, EC 1.14.18.1) was extracted from celery roots (Apium
      graveolens L.) with 0.1 M phosphate buffer, pH 7.0. The PPO was partially
      purified by (NH4)2SO4 and dialysis. Substrate specificity experiments were
      carried out with catechol, pyrogallol, L-DOPA, p-cresol, resorcinol, and
      tyrosine. The Km for pyrogallol, catechol, and L-DOPA were 4.5, 8.3, and 6.2mM,
      respectively, at 25 degrees C. Data for Vmax/Km values, which represent catalytic
      efficiency, show that pyrogallol has the highest value. The optimum pH and
      temperature were determined with catechol, pyrogallol, and L-DOPA. Optimum pH was
      7.0 for catechol and L-DOPA, and 7.5 for pyrogallol. Optimum temperatures for
      maximum PPO activity were 25 degrees C for pyrogallol, 40 degrees C for catechol,
      and 45 degrees C for L-DOPA. Heat inactivation studies showed a decrease in
      enzymatic activity at temperatures above 60 degrees C. The order of inhibitor
      effectiveness was: L-cysteine > ascorbic acid > glycine > resorcinol > NaCl.

PMID- 15553908
TI  - [Iron storage disease].
AB  - Iron overload causes impaired function of tissues and organs due to the increased
      iron storage in them. Hereditary hemochromatosis is the most frequent hereditary
      metabolic disorder, with lethal outcome without treatment. The genetic disorder
      is a mutation on the short arm of the 6. chromosome, which resulted a cysteine
      tyrosine substitution on the 282. amino acid position (C282Y). This mutation is
      less frequent in the non-Caucasian population, in opposition to the other
      reported mutation (H63D). The risk of the development of the disease is the
      highest in people who are C282Y homozygotes or C282Y/H63D compound heterozygotes.
      The prevalence of hemochromatosis is 1.5-5.9 per thousand. Liver
      disease/cirrhosis, diabetes mellitus and hyperpigmentation are the classic signs
      of the disease. Primer hepatocellular cancer occurs in 30% of patients with liver
      cirrhosis, that it is the most common cause of death among them. The diagnosis is
      based on the detection of iron overload (transferrin saturation, serum ferritin
      level, iron concentration of the liver tissue) and on the genetic examinations.
      Early diagnosis makes the causal therapy possible, which is the removal of the
      iron excess by phlebotomy. Furthermore, the early detection of iron overload
      allows of prevention of the development of the disease. Based in these facts
      population screening seems to be necessary and cost-effective, but further
      studies are required to determine the exact screening strategy.

PMID- 15553909
TI  - [The role of caveolin-1 gene in carcinogenesis].
AB  - Caveolin-1 is responsible for the development of caveolae, which are vesicular
      invaginations of the plasma membrane, and plays a key role in membrane traffic
      and signal transduction. The role of caveolin-1 in carcinogenesis has been a
      subject to numerous investigations, however, the expression pattern and the
      function of caveolin-1 are rather controversial both in gastrointestinal and
      extraintestinal cancers. The vast majority of results based on cancer cell line
      experiments indicate that caveolin-1 might act as a tumor suppressor gene. In
      tumor tissues, however, caveolin-1 seem to fulfill a tumor promoting role, since
      the expression of caveolin-1 is increased when compared to normal tissue
      counterparts. In this review, the authors summarize the results of caveolin-1
      expression in gastrointestinal and extraintestinal cancer emphasizing possible
      future therapeutic implications.

PMID- 15553910
TI  - [Review of our experiences and results with renal cell cancer patients in the
      last five years].
AB  - PATIENTS AND METHODS: The authors have collected and processed data of 307
      patients at Urological Department Semmelweis University, who were treated for
      renal tumour from June 1997 to December 2002. RESULTS: During this process on the
      basis of their work, they formed their opinion of the main steps of diagnostical,
      surgical and conservative therapeutical procedure with patients suffering from
      renal cell cancer. They established the fact that the data is parallel with
      retraceable international literature, therefore this work can be the starting
      point of long term prospective studies. They call attention to the fact that 70%
      of the tumours were recognized without any symptoms, during examination indicated
      for other reasons, due to the widely spreading of ultrasound, computed tomography
      and other imaging techniques. CONCLUSION: The tumours are recognized and removed
      in earlier stages and it is to be hoped that it prolongs their life expectancy,
      and makes the quality of life of our patients much better.

PMID- 15553911
TI  - [Medical implications of the lay concepts of health: children's opinions of
      health and illness].
AB  - INTRODUCTION: Lay concepts of health and illness give additional important
      information to the biomedical models. According to the literature of lay beliefs,
      these concepts significantly affect population's health and illness behaviors and
      their health consciousness. Detecting children's lay concepts of health means a
      special professional challenge since they are not able to think in an abstract
      and systematic way yet, particularly to express this verbally. The draw-and-write
      method, which is based on projective technique, enables us to map children's lay
      concepts of health in their 8-10 years of age. AIMS: The main goal of the present
      qualitative research is to detect 8-11-year-old children's lay concepts of
      health, illness and risks, by using a technique which has already been accepted
      and applied at international level. METHODS: Data collection of the qualitative
      research was going on in two middle sized places of Bekes county (Bekes and
      Korostarcsa), in the second half of 2003. The sample consisted of 128 elementary
      and middle school students (57% males and 43% females) from years 3-4-5, one
      class from each place and school grade. RESULTS: Most children apply a mixture of
      the biomedical and holistic health definitions. Many of them also emphasize the
      role of healthy lifestyle. In this age, health basically is related to infections
      since children possess of own experiences primarily about this type of disease.
      Most frequently children receive information of health and illness from their
      parents and physicians. CONCLUSION: These findings support earlier findings from
      international literature that 9-10-year-old children have a significant base of
      knowledge about health, illness and disease-inducing factors.

PMID- 15553912
TI  - [Combined antiviral treatment in a patient with recurrent chronic hepatitis C
      after liver transplantation].
AB  - BACKGROUND: Hepatitis C virus infection persists after liver transplantation and
      causes recurrent liver injury in the majority of the patients. We report a case
      of orthotopic liver transplantation with more than five years survival despite
      the early recurrence of hepatitis C virus. CASE REPORT: A 49-year old woman
      underwent orthotopic liver transplantation because of liver cirrhosis following
      chronic hepatitis C virus infection. Twelve years before she received blood
      transfusion. The chronic liver disease was diagnosed four years later. However,
      then it was thought to be a drug induced liver damage. After the liver
      transplantation hepatitis C chronic hepatitis recurred within one year. The
      serotype analysis (1b) proved the autoreinfection. The combined antiviral
      treatment (interferon plus ribavirin) resulted significant improvement. She was
      asymptomatic nearly for two years. The liver biopsy showed a significant
      histological improvement. However the virologic response and remission was
      transient. Four years after the transplantation recurrence occurred again. The
      liver biopsy proved cirrhosis. Antiviral therapy with pegylated interferon plus
      ribavirin was started but it had been stopped because of severe cytopenia. Lack
      of adequate antiviral treatment her condition became progressively worse.
      Finally, five years after the transplantation she died because of bilateral
      haemorrhagic ovarian necrosis and severe circulatory insufficiency thanks to the
      low albumin level. CONCLUSIONS: In the case of liver cirrhosis caused by
      hepatitis C virus the liver transplantation could prolongs the life with years.
      The presented case illustrate that the hepatitis C virus injures the transplanted
      liver by autoreinfection. However, the combined antiviral therapy could result
      sustained virologic response in these cases as well. Our patient survived five
      years thanks to the transplantation and the following antiviral therapy.

PMID- 15553913
TI  - Obesity in children and adolescents: guidelines for prevention and management.

PMID- 15553914
TI  - Confusing ethical guidelines dampen pharmaceutical support.

PMID- 15553915
TI  - Effectively detect and manage elder abuse.

PMID- 15553916
TI  - Lyme disease: knowledge is the best prevention.

PMID- 15553917
TI  - Guide to care for patients: Lyme disease.

PMID- 15553918
TI  - Anticoagulation therapy a success with patient-focused model.

PMID- 15553919
TI  - Diet, diabetes, and wound management: how important is glycemic control?

PMID- 15553920
TI  - Rural NP perceptions of barriers to practice.

PMID- 15553921
TI  - In vitro and in vivo activities of acylated derivatives of isoniazid against
      mycobacterium tuberculosis.
AB  - Enzymatic acylation of the antitubercular isoniazid (INH) by N-acetyl
      transferases reduces the therapeutic effectiveness of the drug. Because it
      represents a major metabolic pathway for INH in human beings, such acetylation
      has serious consequences for tuberculosis treatment regimens. Among patients in
      whom this process is efficient, the "rapid acetylators," the resultant chronic
      underdosing of INH may give rise to the development of resistance, as well as
      inadequate therapy. Not much work has been done previously to characterize the
      antitubercular properties of other N2-acylisoniazids. In order to address the
      fundamental issue of the activities of these acylated derivatives of INH, a
      number of such compounds 1a-f were chemically synthesized for investigation by a
      method providing good yield and purity. In experiments in vitro against
      Mycobacterium tuberculosis, these compounds displayed minimum inhibitory
      concentration (MIC) values between several fold and several hundred fold greater
      than that of INH itself, on a molar basis, with some of the more active compounds
      having higher calculated values of log P. Among these derivatives, compound 1b,
      closely homologous to the INH metabolite 1a, N2-acetylisoniazid, provided
      unexpected protection in tuberculosis-infected mice. The authors conclude that
      such close structural congeners of metabolites of INH may serve as significant
      leads in antitubercular drug discovery and in the exploration of the mode of
      action of INH.

PMID- 15553922
TI  - Conformational analysis of globomycin with a signal peptidase II inhibitory
      activity using molecular dynamics simulation.
AB  - Globomycin (1), a 19-membered cyclic depsipeptide, exhibited an antibiotic
      activity against gram-negative bacteria by inhibiting signal peptidase II in the
      cytoplasmic membrane. Although only one conformation of 1 was observed for the
      crystal structure, it was revealed by 1H NMR spectroscopic analysis that 1 exists
      as a mixture of two rotational isomers in solution (CDCl3 and CD3OD). A
      conformational analysis of 1 was, therefore, performed by high-temperature
      molecular dynamics simulation in combination with 1H NMR analysis to elucidate
      the conformations in solution. The relative ratio of the major and minor isomers
      present, which differs depending on the solvent, was then derived from their
      relative energy differences obtained in the conformational analysis. The
      difference in the relative ratios corresponded with that calculated from the 1H
      NMR analysis. Finally, the predicted conformations in solution were compared with
      that of the X-ray crystal structure to find local and global differences that
      characterize these conformations.

PMID- 15553923
TI  - Predicting acyl-coenzyme A: cholesterol O-acyltransferase inhibitory activity:
      computational approach using topological descriptors.
AB  - Relationship between the topological indices and acyl-coenzyme A:cholesterol O
      acyltransferase (ACAT) inhibitory activity of (aminosulfonyl)ureas has been
      investigated. Three topological indices, Wiener's index--a distance-based
      topological descriptor, molecular connectivity index--an adjacency-based
      topological index, and eccentric connectivity index--an adjacency-cum-distance
      based topological descriptor, were used for the present investigations. A data
      set comprising 41 analogues of substituted (aminosulfonyl)ureas was selected for
      the present studies. The values of wiener's index, eccentric connectivity index,
      and molecular connectivity index for each of the 41 compounds comprising the data
      set were computed using an in-house computer program. Resultant data were
      analyzed and suitable models were developed after identification of active
      ranges. Subsequently, a biological activity was assigned to each compound using
      these models, which was then compared with the reported in vitro ACAT inhibitory
      activity. Accuracy of prediction using these models was found to vary from a
      minimum of approximately 83% to a maximum of approximately 91%.

PMID- 15553924
TI  - Sulfonate ester hydroxamic acids as potent and selective inhibitors of TACE
      enzyme.
AB  - Sulfonamide hydroxamate derivatives of anthranilic acids are known to be potent
      inhibitors of cell-free TACE enzyme. However, compounds of this structural class
      with both high potency and high selectivity for TACE over matrix
      metalloproteinases (MMPs) are uncommon. Replacement of the sulfonamide
      functionality with an isosteric sulfonate ester has resulted in a series of
      sulfonate ester hydroxamates, 2a-e, with excellent activity against TACE and
      excellent selectivity over MMP-1 and MMP-13. Although compounds 2a-e possess good
      permeability in a PAMPA assay, they are only weakly active as inhibitors of
      lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production in
      human monocytic THP-1 cells. Protein binding affinity also does not predict the
      lack of cellular activity for these analogs.

PMID- 15553925
TI  - Structural bioinformatics and QSAR analysis applied to the acetylcholinesterase
      and bispyridinium aldoximes.
AB  - The methods of bioinformatics, molecular modelling, and quantitative structure
      activity relationships (QSARs) using regression and artificial neural network
      (ANN) analyses were applied to develop safer aldoxime antidotes against poisoning
      by organophosphorus (OP) agents with high, mean, and low aging rates. We start
      here from a molecular modelling of the mouse AChE at an atomistic level. Aim is
      to predict qualitatively the structural requirements of an aldoxime that shows an
      unique reactivating activity against the three classes of OPs. An antidotal
      action should occur by a three-site mechanism: the aldoxime groups of the first
      pyridinium ring should point towards the catalytic site, and the second
      pyridinium ring and its substituents should be anchored at the peripherical and
      anionic subsites. Based on this model, it is predicted that a suitable
      substituent is based on an arginine-like moiety. Then, an ANN-based QSAR analysis
      using a training set of aldoximes with known structure and activities was
      applied. Its input layer consisted of seven nodes: the group-membership
      descriptors that parameterize the type of the OP, the logarithms of the
      distribution coefficients at pH 7.4 and their squared term, the lowest unoccupied
      molecular orbital (LUMO) energies, the scaled molar refractions of the
      substituents, and their squared term. It was shown that the qualitative
      prediction made by molecular modelling can be quantified by an ANN prediction.

PMID- 15553926
TI  - HIV-1 reverse transcriptase variants: molecular modeling of Y181C, V106A, L100I,
      and K103N mutations with nonnucleoside inhibitors using Monte Carlo simulations
      in combination with a linear response method.
AB  - The energies and physical descriptors for the binding of 21 novel 1-(2,6
      difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazole (BPBI) analogs to HIV-1
      reverse transcriptase (RT) variants Y181C, L100I, V106A, and K103N have been
      determined using Monte Carlo (MC) simulations. The crystallographic structure of
      the lead compound, 4-methyl BPBI, was used as a starting point to model the
      inhibitors in both the mutant bound and the unbound states. The energy terms and
      physical descriptors obtained from the calculations were reasonably correlated
      with the respective experimental EC50 values for the inhibitors against the
      various mutant RTs. Using the linear response correlations from the calculations,
      2 novel BPBI inhibitors have been designed and simulations have been carried out.
      The results show the computed deltaG(binding) values match the experimental data
      for the analogs. Given the ongoing problem with drug resistance, the ability to
      predict the activity of novel analogs against variants prior to synthesis is
      highly advantageous.

PMID- 15553927
TI  - QSAR modeling of anti-HIV activities of alkenyldiarylmethanes using topological
      and physicochemical descriptors.
AB  - Three series of anti-HIV data (reverse transcriptase inhibitory activity,
      cytopathicity data, and cytotoxicity data) of alkenyldiarylmethanes were modeled
      with physicochemical, topological and structural descriptors by multiple
      regression analysis using principal component factor analysis as the data pre
      processing step. Molar refractivity was found to be a significant contributor in
      modeling all three data sets. Apart from this, partition coefficient, E-state
      index, valence connectivity and indicator parameters were important in modeling
      different activity series. The final relations were of moderate to good quality
      as evidenced from regression statistics (R2 values ranging 66-75%) and leave-one
      out cross validation data (Q2 values ranging 54-70%).

PMID- 15553928
TI  - Coronary stents reduce restenosis and repeat revascularizations and may also
      improve survival.

PMID- 15553929
TI  - The decline in cardiovascular disease: there is still room for improvement.

PMID- 15553930
TI  - Angioplasty and stents in coronary artery disease: a systematic review and meta
      analysis.
AB  - OBJECTIVES: To undertake a systematic review of the clinical effectiveness of
      routine percutaneous transluminal coronary angioplasty (PTCA) plus stenting vs
      PTCA alone. DATA SOURCES: MEDLINE; EMBASE; Science Citation Index; The Cochrane
      Library; cardiovascular journals and conference proceedings; Internet resources
      (including industry supported web pages); and reference lists of included studies
      and relevant reviews. REVIEW METHODS: Study selection included published and
      unpublished randomized controlled trials (RCTs) comparing the use of coronary
      stents to PTCA. Outcome measures assessed included death, acute myocardial
      infarction (AMI), event rate (such as major cardiac adverse events (MACE) or
      other composite measures), and binary restenosis (BR). Data extraction and
      quality assessment were conducted according to internationally recognized
      methods. Data synthesis included meta-analysis of assessed outcomes, reported as
      odds ratios (ORs). RESULTS: Fifty RCTs involving 16,500 patients met the
      inclusion criteria (39 full articles, 11 abstracts). Of these, 23 studies
      compared stenting with PTCA in patients with non-specific coronary artery disease
      (CAD), 11 compared stents with PTCA following AMI, 8 included patients with small
      coronary arteries and 8 included patients whose vessels had chronic total
      occlusion. There were no differences in rates of death or AMI. There were
      reductions in the rates of MACE (death, AMI or revascularization) with stents
      compared to PTCA (at 6 months, for non-specific group OR: 1.64, 95% CI 1.44-1.87;
      for AMI group OR: 2.36, 95% CI 1.92-2.89; for small vessel group OR: 1.38, 95% CI
      1.10-1.74; at 12 months, for non-specific group OR: 1.31, 95% CI 1.11-1.55; for
      AMI OR: 2.26, 95% CI 1.47-3.46). Reporting of combined major adverse cardiac
      events was inconsistent across studies. Most events were revascularizations that
      may have been partly driven by protocol-required angiograms. Stents reduced BR
      rates at angiogram at 6 months compared to PTCA in all groups. CONCLUSION: We
      found no differences in mortality or AMI, but the studies were not powered to
      identify changes in these endpoints. Coronary stenting is associated with reduced
      restenosis and combined adverse cardiac events, primarily revascularizations.
      However, the frequency of revascularization may have been distorted by protocol
      dictated angiography.

PMID- 15553932
TI  - Trends in the incidence of acute myocardial infarction and stroke: a 21-year
      follow-up of the Oslo study.
AB  - OBJECTIVES: To explore changes in the incidence of fatal and nonfatal myocardial
      infarction (MI) and stroke in the same male population over two decades. DESIGN:
      Men aged 40-49 born in the years 1923-1932 (N= 16,209) resident in Oslo
      participated in a cardiovascular screening programme in 1972-1973. Nonfatal cases
      of MI and stroke were obtained from hospital records and causes of death were
      ascertained by linkage to Statistics Norway. The closing date was December 31,
      1993. RESULTS: The cohort had a lower mortality rate than the general Norwegian
      population. First nonfatal and fatal MIs declined in each age and birth cohort
      during the entire follow-up. The incidence of nonfatal and fatal stroke decreased
      about 10 years after the initial screening. The risk of men with Rose
      questionnaire-based symptoms of angina or claudication was between that of
      healthy men and men with established cardiovascular disease or diabetes.
      CONCLUSIONS: There has been a reduction in both nonfatal and fatal incident cases
      of MI and stroke 10 years later indicating a pronounced change in all age groups
      and a lasting change throughout the period of follow-up. The Rose questionnaire
      predicted both future stroke and MI.

PMID- 15553931
TI  - Blood platelet count and reactivity are associated with restenosis 6 months after
      coronary angioplasty.
AB  - OBJECTIVES: Restenosis occurs in 40-50% of patients treated with percutaneous
      transluminal coronary angioplasty (PTCA). Some data indicate that platelet
      derived growth factor (PDGF) plays a pathogenetic role. The aims of the present
      study were to measure the plasma levels of PDGF across the coronary circulation
      during PTCA and relate them to the development of restenosis. DESIGN AND RESULTS:
      Blood samples from the aortic root and coronary sinus were drawn simultaneously
      before, and after completed PTCA in 26 patients. Plasma levels of PDGF and beta
      thromboglobulin (BTG), as well as platelet counts were measured. Restenosis was
      evaluated by quantitative coronary angiography after 6 months. Significant
      increases both in PDGF and BTG were encountered in the aortic root after PTCA in
      patients who developed restenosis as compared to patients without restenosis.
      Patients who developed restenosis also had significantly higher platelet counts
      compared to those without. CONCLUSION: Increases in plasma PDGF and BTG in the
      aortic root after PTCA seem to be markers for restenosis 6 months after PTCA.
      This finding may strengthen the hypothesis that platelets contribute to the
      process of restenosis.

PMID- 15553933
TI  - Clustering of cardiovascular risk factors. time trends during 28 years.
AB  - OBJECTIVES: To assess the development in frequency and clustering of
      hypertension, hypercholesterolaemia, high body mass index (BMI), physical
      inactivity and tobacco smoking in the period 1964-1992, and to evaluate any sex
      and age differences. DESIGN: Five cross-sectional investigations on
      cardiovascular risk factors performed in 1964, 1978, 1982-1984, 1986-1987 and
      1991-1992 comprising random samples in a suburban area of Copenhagen, Denmark.
      Physical activity during leisure time and smoking habits were assessed by self
      administered questionnaire. Blood pressure, weight, height and serum total
      cholesterol were measured according to WHO standards. RESULTS: A total of 8644
      persons aged 30, 40, 50 and 60 years participated with an equal number of men and
      women. Women had fewer risk factors than men and younger persons had fewer risk
      factors than older persons. In the period 1964-1992 there was a decreasing number
      of risk factors. The 50 year olds show a sex difference in the period 1982-1992,
      whereas there was no sex difference among the 60 year olds. Tobacco smoking was
      the most common risk factor. BMI > 27.5 has become more and more frequent
      throughout the period, especially in men. The BMI has conquered third place in
      all age groups. The association of BMI > 27.5 and sedentary leisure time physical
      activity has become the most frequent. CONCLUSION: Clustering among risk factors
      decreased over time in both sexes. The association of elevated BMI and sedentary
      leisure time activity may contribute to the rising frequency of chronic disease
      such as diabetes mellitus and cardiovascular disease.

PMID- 15553934
TI  - Influence of diabetes on long-term outcome among unselected patients with acute
      coronary events.
AB  - OBJECTIVE: The aims of this study were to investigate the prognostic influence of
      diabetes after an episode of unstable angina pectoris or non-Q-wave myocardial
      infarction (MI) and to investigate whether diabetes is independently associated
      with increased short- and long-term mortality risk following these episodes.
      DESIGN: Consecutive patients with a diagnosis of unstable angina pectoris or non
      Q-wave MI, admitted to the Coronary Care Unit at Ostra Hospital, Goteborg, Sweden
      during 1988-1998 were included. The primary endpoint was 2-year mortality
      collected from the Swedish cause-specific mortality register. RESULTS: The study
      included 4341 patients, 722 (17%) had diabetes. Diabetes was associated with
      increased mortality during initial hospitalization (10.2% vs 5.7%, p < 0.0001),
      after 30 days (13% vs 7.5%, p < 0.0001), and at 2 years (33.7% vs 20.2%, p <
      0.0001). After adjustment for potentially confounding factors, diabetes remained
      an independent predictor of 2-year mortality following unstable coronary
      syndromes, the hazard ratio (HR) of death (HR = 1.6; 95% CI 1.4-1.9).
      CONCLUSIONS: Among patients with unstable coronary syndromes, diabetes is an
      independent risk factor associated with increased mortality during
      hospitalization, short- and long-term follow-up.

PMID- 15553935
TI  - Effects of coronary artery bypass related conduction defects: a 10-year follow-up
      study.
AB  - OBJECTIVES: The aim of this study is to determine the long-term prognostic
      significance of new permanent conduction defects (CDs) related to coronary artery
      bypass grafting (CABG), and to assess predisposing factors for increased
      mortality after CABG. DESIGN: One hundred and eighty patients who underwent an
      elective CABG without any evidence of preoperative CDs were followed on average
      for 9.6 years. Long-term outcome was observed in terms of Kaplan-Meier survival
      analysis, and several potential pre-, intra- and postoperative factors for
      increased mortality were analysed using the Cox regression model. RESULTS: Sixty
      three (35.0%) of the patients developed a new CD (CD+ group) before hospital
      discharge. Early (<30 days) and long-term (>30 days) survival rates were 98.9 and
      86.1%, respectively. The long-term survival in CD+ patients was significantly
      lower that in CD- patients (77.8% vs 90.4%, p = 0.02). However, cardiac survival
      in CD+ patients and CD- patients did not differ from each other (88.9% and 92.3%,
      respectively, p=NS). Five independent predictors for increased all cause
      mortality were identified: diabetes (relative risk ratio 5.99 [2.43-14.78]),
      number of distal anastomoses (3.20 [1.30-7.88]), a new intraoperative conduction
      defect (2.83 [95% CI 1.24-6.49]), preoperative ejection fraction <50% (2.60 [1.08
      6.27]) and perfusion time (1.02 [1.01-1.03]). CONCLUSIONS: Excellent survival
      rates can be obtained 10 years after CABG. CDs were not related to increased
      cardiac mortality. The appearance of preoperative diabetes, intraoperative
      perfusion time, number of distal anastomoses performed, CABG derived permanent
      CDs and low preoperative ejection fraction are associated with higher all cause
      mortality during the long-term follow-up.

PMID- 15553936
TI  - Endothelin and effects of endothelin-receptor activation in the mammary and
      radial artery.
AB  - OBJECTIVE: To determine the tissue content and endothelin-receptor
      characteristics of endothelin-1 in the radial artery in relation to the internal
      mammary artery. DESIGN: Endothelin-1 content was quantified in the radial artery
      and the internal mammary artery. Both arteries were exposed to endothelin-1 and
      agonists of the endothelin A and B receptors. RESULTS: The highest level of
      endothelin-1 was found in the radial artery. Endothelin-1 contracted both
      arteries. The contraction was sensitive to endothelinA-receptor agonism and
      enhanced in both arteries by inhibition of prostacyclin and nitric oxide
      formation. In the internal mammary artery the endothelinB-receptor agonist caused
      an endothelinA-receptor sensitive contraction augmented by inhibition of nitric
      oxide and prostacyclin. However, in the radial artery this contraction was only
      observed in the presence of inhibition of nitric oxide and prostaglandin.
      CONCLUSION: The highest endothelin-1 content was found in the radial artery. The
      functional effects of endothelin-1 in the radial artery were similar to that in
      the internal mammary artery, mediated by predominantly endothelinA-receptor
      activation causing vasoconstriction. Selective endothelinA-receptor blockade may
      prove beneficial in preventing graft spasm in the radial as well as the internal
      mammary artery.

PMID- 15553937
TI  - Cardioprotection with resveratrol pretreatment: improved beneficial effects over
      standard treatment in rat hearts after global ischemia.
AB  - OBJECTIVE: The major objective of the present study is to evaluate the potential
      role of resveratrol (RVT), a natural antioxidant found in grapes and red wine, in
      protecting the myocardium from the deleterious effects of ischemia-reperfusion
      (I/R) injury using isolated rat hearts. METHODS: Langendorff perfused isolated
      rat hearts were subjected to 60 min of global ischemia following 60 min of
      reperfusion. RVT was given according to chronic pretreatment and/or acute
      treatment protocols. Animals received RVT at the dose of 20 mg/kg via an
      intragastric tube for 14 days before the experiment and/or at the infusion
      concentration of 10 microM for 30 min before the onset of ischemia. The
      myocardial postischemic recovery was compared using hemodynamic data (peak
      systolic pressure, end diastolic pressure, and +dP/dtmax), coronary flow,
      biochemical parameters (LDH, CK-MB, cTnI, myoglobin) from coronary effluent, and
      oxidative stress markers (MDA, GSH, carbonyl) from heart tissue homogenates in
      each group. RESULTS: RVT pretreatment and treatment protocols have provided
      increased preservation in myocardial recovery following global ischemia compared
      to a non-treated group. Furthermore, the ischemic damage of myocardium was
      significantly lower in chronic pretreated rats than in the acutely treated group.
      In contrast, no significant difference was observed in cardioprotective effects
      of RVT between the only pretreated group, and both the pretreated and treated
      group throughout reperfusion. CONCLUSION: The findings from this study indicate
      that RVT has potent cardioprotective properties against I/R injury in rat hearts.
      The study also highlighted that the administration of RVT, as pretreatment, has
      amplified the beneficial effects over the standard treatment.

PMID- 15553938
TI  - What's your diagnosis: chronic displaced greater tuberosity fracture of the
      proximal humerus.

PMID- 15553939
TI  - Bilateral spontaneous quadriceps tendon ruptures in a patient with Bardet-Biedl
      syndrome.

PMID- 15553940
TI  - Academic health centers.

PMID- 15553941
TI  - Medial patellofemoral ligament reconstruction.

PMID- 15553942
TI  - The use of a two C-arm technique in the treatment of slipped capital femoral
      epiphysis.

PMID- 15553943
TI  - Michael Mont on metal-on-metal hip resurfacing arthroplasty.

PMID- 15553944
TI  - Alternatives for MRSA treatment in the pediatric patient.

PMID- 15553945
TI  - Management of first-time patellar dislocations.

PMID- 15553946
TI  - Cervical spine surgery.

PMID- 15553947
TI  - Primary malignant tumors of the cervical spine.

PMID- 15553948
TI  - Hippocratic beliefs on spine and spinal cord injuries: new or old notions?

PMID- 15553949
TI  - Factors associated with good outcome using lateral mass plate fixation.
AB  - The immediate and long-term outcomes of 70 consecutive patients who underwent
      subaxial lateral mass fixation between June 1996 and June 2001 were reviewed.
      Intraoperative fluoroscopy and somatosensory evoked potential (SEP) monitoring
      were used in all patients. Immediate postoperative computed tomography (CT) was
      performed to determine screw trajectory and placement. Follow-up ranged from 2 to
      7 years. Postoperative CT showed 206 (58%) of 356 screws had unicorticate and 42%
      bicorticate purchase. Furthermore, 96 (27%) screws had suboptimal trajectory, but
      only 5 of these screws minimally penetrated the foramen transversarium without
      resultant vascular or neurological sequelae. A sudden unilateral intraoperative
      SEP amplitude decrease during screw placement in 2 patients resolved with screw
      removal and alteration of screw trajectory. The overall fusion success rate was
      91.5% and screw pull-out developed in 2 patients. The recommended drilling
      technique and trajectory (15 degrees - 25 degrees rostral in the sagittal plane,
      20 degrees - 30 degrees lateral in the axial plane), supplemented bone grafting,
      and intraoperative SEP monitoring are all associated with good screw placement,
      fusion, and neurological outcome and are recommended for all lateral mass fusion
      procedures.

PMID- 15553950
TI  - Surgical decompression for cervical spondylotic myelopathy: correlation between
      operative outcomes and MRI of the spinal cord.
AB  - Forty-two patients who underwent decompressive surgery for cervical spondylotic
      myelopathy were studied. The pre- and postoperative magnetic resonance imaging
      (MRI) findings and the Japanese Orthopedic Association score were analyzed to
      evaluate whether the different appearances of intramedullary high-signal
      intensity on T2-weighted MRI are related to the surgical prognosis. Magnetic
      resonance imaging signal intensities were classified as type 0 if no
      intramedullary high-signal intensity on T2-weighted images was noted, type 1 if
      high-signal intensity involved only one segment, and type 2 if high-signal
      intensity extended over two segments. Statistical analyses of the recovery ratio
      showed that type 0 and type 1 intramedullary high-signal intensity indicates
      better prognosis than type 2.

PMID- 15553951
TI  - Cervicobrachialgia and pancoast tumor: value of standard anteroposterior cervical
      radiographs in early diagnosis.
AB  - Ten patients diagnosed with Pancoast tumor were studied retrospectively. The
      definitive diagnosis was made between 2 and 24 months after the onset of pain.
      Pain localization was hard to pinpoint; some patients reported pain in four
      different sites (neck, shoulder, arm, and scapula). Five patients had previously
      been diagnosed with degenerative, inflammatory, or infectious diseases of the
      cervical spine or shoulder. In the remaining five patients, the diagnosis was
      made during the first clinical visit. In three patients, an orthopedic surgeon
      made the diagnosis by viewing a standard anteroposterior (AP) cervical
      radiograph. The radiographic evidence arousing suspicion of a Pancoast tumor was
      the lack of pulmonary air at the top of the affected lung. Furthermore, a
      parallel study was conducted on 100 consecutive patients seeking treatment for
      neck pain. By examining the AP radiographs of their cervical spines, the third
      rib and the top of both lungs were observed in all cases. This study stresses the
      value of standard AP cervical radiographs in the diagnosis of Pancoast tumor.

PMID- 15553952
TI  - Multiple fractures of the axis.
AB  - Multiple fractures of the axis are not common lesions. A retrospective study was
      performed to identify the different fracture patterns and to analyze the
      incidence of these injuries and their long-term behavior. The medical records of
      674 consecutive patients with fractures of the cervical spine were reviewed. Nine
      (1%) of 674 patients (6 men and 3 women) had multiple fractures of the axis. Mean
      patient age was 48 years. The most common lesion was a combination of traumatic
      spondylolisthesis with either an odontoid process or a teardrop fracture of the
      axis body. All patients were treated conservatively with an excellent or good
      outcome at mean 12-year follow-up (range: 2-18 years). Computed tomography was
      the imaging modality of choice for the correct diagnosis of these rare lesions.

PMID- 15553953
TI  - Transmandible approach for the treatment of upper cervical spine metastatic
      tumors.
AB  - The transmandible tongue-splitting approach is a useful and safe procedure for
      treating secondary lesions of the upper cervical spine, with only minor cosmetic
      and functional impairment. This method requires a team approach and has the
      advantage of enhancing the surgical exposure, thus allowing for resection and
      stabilization on more levels. Two patients with metastases in the upper cervical
      spine were treated using this approach. In view of a relatively long life
      expectancy, a marginal resection was performed. The residual instability required
      a combined approach and internal fixation. Both patients were ambulant,
      neurologically intact, and pain free 24 and 26 months postoperatively.

PMID- 15553954
TI  - Tumoral calcinosis of the popliteal space.

PMID- 15553955
TI  - Sternoclavicular joint infection and mediastinitis originally attributed to
      concomitant rotator cuff pathology.

PMID- 15553956
TI  - Rapidly destructive coxarthropathy with osteonecrosis and osteoporosis caused by
      Cushing's syndrome.

PMID- 15553957
TI  - An incredible personal and professional sacrifice.

PMID- 15553958
TI  - Almost 300,000 children (ages 5 to 15) with disabilities in California.
AB  - The 2000 Census data on the numbers of children with disabilities in California
      are presented by city, metropolitan area and congressional districts. There are
      numerous difficulties associated with the delivery of dental care to these
      youngsters with special needs. Nevertheless, if all dentists were willing to
      help, each practitioner would need to care for 13 of these youngsters. This paper
      will cover demographics, children with disabilities, dental services, and
      politics.

PMID- 15553959
TI  - On the diagnosis and management of neurocutaneous syndrome, a toxicity disorder
      from dental sealants.
AB  - Neurocutaneous syndrome, a newly discovered toxicity disorder, is characterized
      by neurological sensations, pain, depleted energy, and memory loss as well as
      itchy cutaneous lesions that may invite various opportunistic infections.
      Components in the calcium hydroxide dental sealants Dycal, Life and Sealapex have
      been identified as sources of the observed symptoms. Sulfonamide and neurological
      toxicity issues are discussed, and three case histories are presented. Additional
      notes on zinc oxide, Fynal, IRM, and Sultan U/P sealers are also included.
      Diagnostic and management protocols at the Parasitology Center, Inc., are
      proposed.

PMID- 15553960
TI  - Evaluation of apically extruded debris in conventional and rotary instrumentation
      techniques.
AB  - OBJECTIVE: The purpose of this in vitro study was to compare two common
      techniques, conventional and rotary instrumentation, in debris extrusion. METHODS
      AND MATERIALS: Two hundred mature human teeth with mature apices and less than 15
      degrees of root curvature as determined by Schneider's method were selected for
      use. Teeth were randomly divided into four groups of 50 teeth each and prepared
      using step-back instrumentation and profile 4 percent Taper Series 29 rotary
      system at three different speeds: 1,000 rpm, 8,000 rpm and 24,000 rpm. All of the
      speeds were reduced by contra angle to 1/6 rpm. Extruded debris were collected on
      pre-weighed vials containing distilled water through the apical foramen during
      instrumentation. The vials were then dried in a microwave oven at 150 degrees
      Celsius and weighed again. The difference was recorded as "the weight of the
      extruded debris." Eight control vials, two for each group, were weighed and
      filled with distilled water, dried, and reweighed. The mean weight of extruded
      debris for each group was statistically analyzed. T-student, unilateral variance
      analysis and Pearson tests were used in this study. RESULTS: Step-back
      instrumentation (Group 1) produced significantly more debris than other groups.
      The difference in the amount of debris produced among rotary groups was not
      significant. CONCLUSION: Rotary technique could reduce the amount of debris
      extrusion.

PMID- 15553961
TI  - Kiev: an unexpected transition.

PMID- 15553962
TI  - Disposal fees and extended warranties: milking the cash cow.

PMID- 15553963
TI  - Unsupported people.

PMID- 15553964
TI  - How do you feel?

PMID- 15553965
TI  - Power to the people.

PMID- 15553966
TI  - Breaking the habit.

PMID- 15553967
TI  - It's evident some staff think Alfred is 'bogus' because parts of his story don't
      appear to add up.

PMID- 15553968
TI  - When your benefit is stopped your credit rating with the lender of last resort
      goes with it.

PMID- 15553969
TI  - A hard act.

PMID- 15553970
TI  - Faith, hope and community.

PMID- 15553971
TI  - How well are we doing?

PMID- 15553972
TI  - They should have listened.

PMID- 15553973
TI  - Springing the poverty trap.

PMID- 15553974
TI  - Permissive parenting is not the problem; the problem is putting profits before
      children.

PMID- 15553975
TI  - This life.

PMID- 15553976
TI  - A letter from your President.

PMID- 15553977
TI  - Herpesviruses, the missing link between gingivitis and periodontitis?
AB  - Herpesviruses appear to assume a major etiopathogenic role in various types of
      destructive periodontal disease. Human cytomegalovirus (HCMV), Epstein-Barr virus
      (EBV) and HCMV-EBV co-infection are closely associated with disease-active
      periodontitis in juveniles and adults, with acute necrotizing ulcerative
      gingivitis in children, and with periodontal abscesses. In particular, HCMV
      reactivation in periodontitis lesions seems to be linked to advancing disease.
      HCMV infects periodontal monocytes/macrophages and T-lymphocytes, and EBV infects
      periodontal B-lymphocytes. Herpesvirus-infected inflammatory cells generate a
      great variety of pro-inflammatory cytokines and may possess diminished ability to
      defend against bacterial challenge. Herpesvirus-associated periodontal sites tend
      to harbor elevated levels of periodontopathic bacteria, including Dialister
      pneumosintes, Porphyromonas gingivalis, Tannerella forsythia, Prevotella
      intermedia, Prevotella nigrescens, Treponema denticola, Campylobacter rectus and
      Actinobacillus actinomycetemcomitans. In summary, the available data suggest that
      periodontitis occurs more frequently and progresses more rapidly in herpesvirus
      infected than in non-infected periodontal sites. An infectious disease model
      based on herpesvirus-bacteria-host immune response interactions is presented to
      explain how a gingivitis lesion or a stable periodontal site with increased
      probing depth may convert into a tissue-destroying periodontitis lesion.

PMID- 15553978
TI  - Effect of lifestyle on periodontal disease status in diabetic patients.
AB  - Lifestyle and socioeconomic status have been associated with the disease status
      of diabetic patients. However, there have been few reports on the relationship
      between these factors and the periodontal condition of diabetics. We assessed the
      association between disease status and lifestyle of diabetic patients and
      clinical features of advanced periodontitis such as deep probing depths and
      severe alveolar bone loss. Fifty-seven diabetic patients were examined in this
      study. Clinical assessment of probing pocket depth and radiographic alveolar bone
      loss was performed. Data regarding diabetic status and lifestyle of the diabetic
      patients were also recorded and statistically analysed by logistic regression.
      Drinking habits and high values of hemoglobin A1c (HbA1c) (>9.0%) were
      significantly associated with deep probing depth. The odds ratios (OR) of these
      factors were 7.72 (95% confidence interval (CI), 1.80 to 33.19), and 6.10 (95% CI
      = 1.23 to 30.25), respectively. Presence of complications such as retinopathy (OR
      = 8.86, 95% CI, 1.99 to 39.40), irascible behaviour (OR = 8.40, 95% CI = 1.33 to
      53.17) and high value of HbA1c (OR = 4.94, 95% CI = 1.14 to 21.46) were
      significantly related to mean advanced alveolar bone loss. Only the high value of
      HbA1c (OR = 3.53, 95% CI = 1.06 to 11.73) was detected as a significant factor
      related to advanced periodontitis, characterised by more than 50% mean alveolar
      bone loss, or two or more teeth with probing depth greater than 6 mm. In
      conclusion, drinking habit and irascible behaviour are correlated with the
      periodontal disease condition of diabetic patients, in addition to a high value
      of HbA1c (>9.0%). Lifestyle and psychosocial stress may affect the periodontal
      disease status of diabetic patients.

PMID- 15553979
TI  - Oral and dental health among inpatients in treatment for alcohol use disorders: a
      pilot study.
AB  - Individuals undergoing treatment for alcohol use disorders exhibit increased risk
      for impaired oral health. We conducted a study to assess oral health and
      demographic characteristics of inpatients under treatment for alcohol use
      disorders. MATERIALS AND METHODS: Thirty-four inpatients, 24 male and 10 female,
      with diverse ethnicity, were recruited in a rehabilitation center for alcohol use
      disorders in Buffalo, NY. Before undergoing oral examination, subjects completed
      a questionnaire on dental hygiene, associated behaviors, and demographic
      characteristics. Information regarding patients' oral health was collected using
      plaque, gingival, and decayed, missing or filled teeth (DMF) indices, and by
      examining soft tissue and evaluating signs of abrasion, erosion, and attrition.
      Statistical analysis determined prevalence and descriptive characteristics.
      RESULTS: Alcohol intake for the population was, on average, 45.7 drinks/week, and
      61.8% had smoked cigarettes within the past month. Patients were missing 15.1% of
      their teeth. Of teeth examined, 13.5% had dental caries. Prevalence of soft
      tissue abnormalities was 35.3%, prevalence of tooth erosion was 47.1%, and
      prevalence of moderate/severe gingival inflammation was 82.3%. Although study
      participants reported brushing at least once a day, 70.6% of subjects presented
      with heavy dental plaque accumulation. Most participants (85.3%) described the
      condition of their mouth and teeth as fair or poor. Finally, we observed a
      satisfactory participation rate among those who qualified for the study.
      CONCLUSION: Oral examination showed significant levels of dental caries, gingival
      inflammation, soft tissue abnormalities, and tooth erosion. In addition, this
      study indicates that patients undergoing treatment for alcohol use disorders
      evidence poor oral health, and are at heightened risk for the development of
      periodontal disease.

PMID- 15553980
TI  - Cemento-ossifying fibroma: case report and review of the literature.
AB  - Although the neoplastic nature of intrabony cemento-ossifying fibromas is beyond
      dispute, controversy exists regarding the soft tissue counterpart. Peripheral
      cemento-ossifying fibroma has been referred to by a variety of terms depending on
      whether it is accepted as being a true odontogenic tumor or a reactive gingival
      overgrowth. The management of a patient with peripheral cemento-ossifying fibroma
      in the masticatory mucosa of the anterior region of the maxilla is presented. The
      differential diagnosis of reactive gingival overgrowths with and without
      calcification is discussed.

PMID- 15553981
TI  - HIV/AIDS in Southern Africa: a major problem.

PMID- 15553982
TI  - Why do many NMDA antagonists fail, while others are safe and effective at
      blocking excitotoxicity associated with dementia and acute injury?
AB  - Similar to drug development programs for stroke and traumatic brain injury,
      programs developed for Alzheimer's disease (AD) have not been very effective in
      treating dementia. Recently, researchers have explored modulating excitatory
      synaptic neurotransmission via the N-methyl-D-aspartate receptor (NMDAR) to treat
      AD. However, many investigators doubt that NMDA antagonists are safe and
      effective for treating persons with AD because they have failed in stroke and
      trauma programs. This article explores the role of NMDA-mediated excitotoxicity
      in AD, reviews how the NMDAR functions, highlights the side effects and alternate
      signaling pathways that are initiated from NMDAR activation, provides examples of
      NMDA antagonists that do not exhibit the typical side effects, and discusses why
      some NMDA antagonist compounds are effective and safe in limiting cascades of
      excitotoxicity in dementia or acute brain injury.

PMID- 15553983
TI  - Statin use and hippocampal volumes in elderly subjects at risk for Alzheimer's
      disease: a pilot observational study.
AB  - Statins are investigational therapies for preventing or treating Alzheimer's
      disease (AD) and mild cognitive impairment (MCI). Hippocampal atrophy is a
      characteristic feature of MCI and AD. This study analyzed cross-sectional data
      from 246 nondemented elderly subjects to test the effect of lipid lowering agent
      (LLA) therapy on cognition and brain magnetic resonance imaging (MRI) measures of
      white matter lesions and hippocampal volume. The study also compared rates of
      hippocampal volume change over two and four years in a smaller subset. At
      baseline, LLA users were younger, better educated, more likely to be male, and
      had higher cognitive scores. Cognitive performance also varied by age and gender,
      and MRI measures varied by age. After adjusting for these differences, the effect
      of LLA use on baseline cognition, baseline hippocampal volume, and baseline white
      matter lesion scores was not significant. The effect of LLA use on hippocampal
      volume loss at two-year and four-year follow-ups was also not significant. This
      study is the first to examine statin effects on brain atrophy measured by MRI. In
      this cohort, statin use was not associated with rate of change of hippocampal
      volume. While the study was limited by a relatively small number of statin users,
      the findings seem consistent with three prior randomized trials that found no
      cognitive benefits for statins in nondemented subjects. Prospective studies in
      both nondemented and AD subjects may provide more conclusive answers.

PMID- 15553984
TI  - Significance of behavioral pathology on functional performance in individuals
      with Alzheimer's disease and related dementias.
AB  - Insight on the role of frontal systems functioning has led to the development of
      measures targeting behaviors mediated through the prefrontal cortex. The current
      review investigated the relationship of behavioral pathology to functional
      performance in individuals with dementia and discussed the association of
      behavioral pathology and executive dysfunction. Results indicated that both
      behavioral measures and cognitive status were strongly correlated to functional
      performance. However, neither behavioral measure nor cognitive status
      demonstrated a stronger association to functional performance at a greater
      consistency than the other measure. This review has important implications for
      the use of behavior measures by medical practitioners to determine the functional
      status of persons with Alzheimer's disease (AD) and other dementias and the use
      of results obtained by these measures to develop appropriate intervention
      strategies.

PMID- 15553985
TI  - Differences in dementia services and settings across place types and regions.
AB  - People with dementia have complex and unique social, environmental, and
      communication needs arising from impaired cognition. One response to
      dissatisfaction with the medical model of care in nursing homes has been the
      creation of more homelike and social options for care in the community. These
      options include community-based residential facilities and a variety of more
      independent senior dwellings. Staying in residential settings longer may be
      associated with benefits, including decreased financial burden and improved
      quality of life. However, with the boundaries between these place types often
      less than clearly drawn, it has become increasingly difficult to anticipate the
      specific services and environmental features provided by each. It is also
      difficult to effectively match facilities to the specific needs of older persons
      with dementia. Even social workers responsible for placements, especially in
      urban areas, may not be able to visit all local residential options. To better
      understand these new venues for dementia care, this study explored the range of
      services and settings available to people with dementia in three different place
      types in five Wisconsin counties: nursing homes, community-based residential
      facilities, and independent senior housing.

PMID- 15553986
TI  - Variation in cost of informal caregiving and formal-service use for people with
      Alzheimer's disease.
AB  - This study used a geographically diverse sample to estimate the total cost of
      informal care and formal services for community-residing Alzheimer's disease (AD)
      care recipients. Baseline data were used for 1200 family caregivers from the
      Resources for Enhancing Alzheimer's Caregiver Health (REACH) study, a multisite
      intervention trial. The replacement-wage-rate approach estimated informal cost.
      Formal services were assigned a cost based on secondary sources. Annual cost per
      care recipient amounted to 23,436 dollars for informal care and 8064 dollars for
      formal services. Variation in informal cost was almost entirely due to
      instrumental activities of daily living (IADLs) assistance. Cross-site
      differences in cost persisted after controlling for caregiver and care-recipient
      characteristics. Geographic variation may suggest regional preferences or
      ethnic/cultural values. Further study is needed to determine whether this
      reflects differences in access or availability or how including a control group
      for care recipients with nondementia diagnoses might have affected these
      findings.

PMID- 15553987
TI  - Lay person's recommendations about interventions for Alzheimer's disease:
      correlates and relationship to help-seeking behavior.
AB  - The aim of this study was to examine lay persons' beliefs about the helpfulness
      of interventions for Alzheimer's disease (AD) and its correlates. Interviews were
      conducted with 206 Jewish Israeli adults (mean age 59.7), using an experimental
      vignette methodology varying in the severity of the disease. Information
      regarding participants 'recommendations about the helpfulness of 10 interventions
      for the person described in the vignette was elicited. Sociodemographic and
      psychological correlates were examined. We discovered that the lay public
      endorses the use of nonpharmacological treatments more than pharmacological ones.
      Engagement in social activities and participation in a support group were the
      treatment approaches most recommended, while the use of physical restraints and
      isolation were the least recommended. Beliefs about AD treatments were associated
      with help-seeking from professional sources. Advances in the development of
      effective treatments for AD should be accompanied by research into the public's
      understanding of these treatments.

PMID- 15553988
TI  - The ticking meter.

PMID- 15553989
TI  - Air-Rotor Slenderizing (ARS).

PMID- 15553990
TI  - Micro implants in orthodontics.

PMID- 15553991
TI  - Developing dental arch symmetry using the Homeoblock device.

PMID- 15553992
TI  - Simplicity in orthodontic treatment--Part III.

PMID- 15553993
TI  - Avoiding abandonment.

PMID- 15553994
TI  - [Treatment of HIV-1 infected pregnant women].
AB  - Since 1 January 2004, pregnant women in the Netherlands have been universally
      screened for HIV infection. Three HIV-infected, pregnant women aged 28, 24 and 33
      years respectively, illustrate some of the problems that may be encountered in
      this situation, as well as the treatment options available to prevent the
      transmission of HIV from mother to child. The first patient had a positive
      antibody test early in pregnancy for which she did not need treatment, the second
      had a positive antibody test late in pregnancy and the third was seropositive and
      on medication, but had the wish to become pregnant. A vaginal delivery is
      possible when highly active antiretroviral therapy (HAART) of the mother is
      started in good time and the plasma HIV-RNA is < 400 copies/ml at the time of
      delivery. In this situation the risk of transmission is reduced to around 1%.
      However, if HIV infection is diagnosed late in pregnancy or, despite HAART, the
      plasma HIV-RNA is not expected to be < 400 copies/ml, an elective caesarean
      section is scheduled at 38 weeks of pregnancy. In all instances the neonate is
      treated for 28 days with antiretrovirals, as post-exposure prophylaxis. If a
      woman with a known HIV infection wants to become pregnant, the choice of
      antiretroviral regimen and when this is started is determined by her treatment
      history and the potential toxic effects of the medication on the foetus.

PMID- 15553995
TI  - [Carotid endarterectomy indicated in asymptomatic stenosis].
AB  - Carotid endarterectomy (CE) is of proven value for patients with a high-grade
      symptomatic stenosis of the internal carotid artery (ICA). Recently, the
      Asymptomatic Carotid Atherosclerosis Study group showed that in patients with an
      asymptomatic ICA stenosis of more than 60%, CE caused an absolute risk reduction
      of perioperative death or stroke during 5 year follow-up of 5.4% (95% confidence
      interval: 3.0-7.8). Half of these strokes were disabling. The number needed to
      treat to save one patient from death within 30 days or stroke within in the
      following 5 years was 19. Further studies are needed to isolate a group of
      patients that will substantially benefit from the operation. CE is probably most
      effective in males under 75 years of age. A low surgical morbidity and mortality
      is an absolute prerequisite to justify CE for an asymptomatic ICA stenosis.

PMID- 15553996
TI  - [Methods of collecting urine for the determination of microalbuminuria: time for
      consensus].
AB  - In daily practice, collecting urine for the determination of microalbuminuria may
      take place in various ways and several different procedures are often used side
      by side in one institution. Ideally, the collection of urine should be as simple
      as possible for the patient, without losing diagnostic value. Having considered
      the pros and cons of the various procedures, we recommend measurement of the
      albumin-creatinine ratio in the 1st morning urine for both diagnosis and follow
      up. This ratio is reported in gram of albumin per mol of creatinine and sex
      dependent cut-off values must be used when interpreting the results: there is
      microalbuminuria above 2.5 g/mol for men and above 3.5 g/mol for women. If
      microalbuminuria is detected, the investigation should be repeated at least twice
      in a period of a few months in order to establish the degree of microalbuminuria.

PMID- 15553997
TI  - [Optimal breastfeeding to prevent hyperbilirubinaemia in healthy, term newborns].
AB  - In a newborn infant, frequent bowel movements diminish the enterohepatic
      circulation of bilirubin, thereby increasing bilirubin excretion. In breastfed
      newborn infants, the frequency of latching on and administration of supplementary
      feeds are associated with serum bilirubin concentrations. Frequent breast feeding
      (at least 8 times a day) and fewer supplementary feeds will result in increased
      breast milk intake, less weight loss, and lower bilirubin concentrations. In the
      case of a breastfed infant presenting with neonatal hyperbilirubinaemia, the
      advice should be to breastfeed more frequently and to withhold supplementary
      feedings. An icteric newborn infant should be seen and weighed daily. If the
      infant has lost more than 10% of its birth weight, drinks poorly, or fails to
      gain weight despite latching onto the breast frequently, it should be referred to
      the paediatrician for further diagnosis and treatment. To ensure optimal
      production of breast milk during the first days after birth, early latching on is
      recommended, preferably within one hour after birth.

PMID- 15553998
TI  - [Diagnostic image (210). A young woman suffering from abdominal pain].
AB  - A 33-year-old pregnant woman presenting with low abdominal pain was diagnosed
      with left-sided tubal extra-uterine pregnancy, which was surgically removed.

PMID- 15553999
TI  - [Highly active antiretroviral therapy (HAART) in HIV-positive pregnant women in
      the Netherlands, 1997-2003: safe, effective and with few side effects].
AB  - OBJECTIVE: To assess the side effects, safety and efficacy of highly active
      antiretroviral therapy (HAART) in a cohort of HIV-infected pregnant women in the
      Netherlands. DESIGN: Retrospective. METHOD: Data were collected from the medical
      records of HIV-infected pregnant women who received HAART during pregnancy in the
      period 1 January 1997-1 June 2003 at 14 HIV-specialized centres in the
      Netherlands. The inclusion criteria were at least a triple drug regimen and birth
      at 20 or more weeks of gestation. Information was collected about patient
      characteristics, HAART prescribed, side effects, viral load response, mode of
      delivery and HIV-status of the neonate. RESULTS: A total of 267/413 women
      satisfied the inclusion criteria. Most women (n = 199) had not previously
      received anti-retroviral therapy and started HAART between weeks 21 and 28 of the
      pregnancy. The two most frequently used regimens contained nelfinavir (57%) or
      nevirapine (31%). Gastrointestinal side effects were more frequently observed in
      the nelfinavir group, while rash and hepatotoxicity were more frequently reported
      in the nevirapine group. Efficacy and pregnancy outcome were similar in both
      groups. Two infants (0.7%) were HIV-infected. CONCLUSION: HAART regimens
      containing nelfinavir or nevirapine in HIV-infected pregnant women were safe,
      effective and well tolerated.

PMID- 15554000
TI  - [Microalbuminuria in patients with type 2 diabetes mellitus in general practice].
AB  - OBJECTIVE: Determine the prevalence of microalbuminuria in patients with type 2
      diabetes mellitus (DM) in general practice, as an independent risk factor for
      cardiovascular diseases. DESIGN: Prospective, descriptive. METHOD: Data were
      collected on patients with type 2 DM in the Zwolle region of the Netherlands, all
      of whom were being treated by their general practitioner. The inclusion period
      was 1 February 2000-31 January 2001. The study formed part of a larger
      investigation, in which the albumin concentration in a urine sample and the
      albumin-creatinin ratio were determined once per year. A total of 32 general
      practitioners took part in the study. RESULTS: In the general practices studied,
      2094 patients were known with type 2 DM and 1653 (79%) were treated exclusively
      by the general practitioner. Of these 1653 patients, 67 (4%) were excluded and of
      the 1586 invited patients remaining, 1441 (91%) participated. Microalbuminuria
      was present in 33% of the patients and macroalbuminuria in 7% of the patients,
      and the prevalences increased with age: < 50, 50-70 and > 70 years. 18% (6/33) of
      the patients aged < 50 years with microalbuminuria were treated with an ACE
      inhibitor or angiotensin II antagonist compared to 33% (183/548) of patients > or
      = 50 years. 91% (488/539) of the patients > or = 50 years with microalbuminuria
      had hypertension and/or lipid profile abnormalities and 82% (402/488) of them
      were not treated or did not receive adequate treatment for this condition.
      CONCLUSION: Microalbuminuria and macroalbuminuria were present in respectively
      33% and 7% of the patients with type 2 DM in primary care. The treatment of
      hypertension and lipid profile abnormalities was often inadequate. Therefore,
      screening patients aged 50 years and older with type 2 DM for albuminuria is
      justified.

PMID- 15554001
TI  - [Acute generalised exanthematous pustolosis in a 2-year-old girl following
      treatment with amoxicillin].
AB  - A two-year-old girl had had fever for one week, and since the previous day
      general malaise, cutaneous pustolosis with swollen hands and feet. The skin
      condition had developed three days after the start of amoxicillin therapy.
      Laboratory tests at the time of admission indicated an infection. The diagnosis
      was 'acute generalised exanthematous pustulosis' (AGEP). During treatment with a
      soothing lotion, lasting one week, the patient improved and the skin condition
      disappeared. AGEP is characterised by acute onset of a pustular eruption in
      association with fever. It is usually seen after the use of drugs. This is an
      uncommon disease in children.

PMID- 15554002
TI  - [Notifications to the Netherlands Pharmacovigilance Foundation Lareb of the
      expulsion of a vaginal contraceptive ring (NuvaRing) and of pregnancy during the
      use of it].
AB  - Netherlands Pharmacovigilance Foundation Lareb expulsion of the vaginal
      contraceptive ring NuvaRing was reported 8 times between February 2003 and April
      2004. Moreover, in two of these reports pregnancy was reported. In that same
      period, Lareb received 10 more reports of pregnancy during the use of the ring,
      in which expulsion was not mentioned explicitly. Additional information on these
      cases was collected by questionnaire. Expulsion of the ring is described in the
      product information. The ring should then be placed back within 3 h. However, the
      Lareb reports show that expulsion of the ring is not always noticed by the user.
      In those cases the contraceptive efficacy of this method is questionable. The
      physician should be alert to pre-existing risk factors that increase the chance
      of expulsion of the ring, and should provide extra detailed advice about the
      right way of placing the ring, the risk of expulsion and the importance of
      replacing it in time.

PMID- 15554003
TI  - [Less refusal to participate in HIV screening among pregnant women in the
      Amsterdam region since the introduction of standard HIV screening using the
      opting-out method].
AB  - In 2003 the Municipal Health Service in Amsterdam started to screen pregnant
      women for HIV according to the opting-out method. In this method the HIV test is
      routinely included in the prenatal screening along with hepatitis B virus (HBV)
      and syphilis. If the woman does not want to be tested for HIV then she must
      actively opt out of this test. This screening method was chosen because in the
      universal screening method used in 2002, women had to give their explicit consent
      to test for HIV and this led to a high refusal rate (13.6%), especially among
      women from AIDS-endemic countries. After the introduction of the opting-out
      method, the refusal rate fell from 3% in the first quarter of 2003 to 1.4% in the
      last quarter of 2003. None of the women refused to be tested for HBV or syphilis.
      In 2003, the HIV prevalence among pregnant women was 0.3% (35/13.621). The
      experiences with this screening method in Amsterdam were used to implement the
      national opting-out method for HIV screening in pregnant women, which was
      introduced on 1 January 2004.

PMID- 15554004
TI  - [The attending physician and the certificate of natural death in children].

PMID- 15554006
TI  - Both ends of the spectrum. With Bush and Kerry offering such different healthcare
      plans, voters must decide which candidate is better for the nation's health.
AB  - As Election Day approaches, voters concerned about healthcare issues face two
      widely divergent choices in the plans offered by George Bush and John Kerry. If
      Bush wins, the president would seem to face little trouble advancing his agenda,
      while Kerry would likely face a battle from a GOP-controlled Congress.

PMID- 15554005
TI  - [Clinical characteristics and management of adolescents admitted to the emergency
      ward for alcohol intoxication in the region of The Hague during the period 1999
      2001].

PMID- 15554007
TI  - Hospitals on winning streak. A charity-care suit dismissed; consolidation denied.

PMID- 15554008
TI  - Trouble in paradise. Hospitals draw scrutiny for use of offshore insurers.

PMID- 15554009
TI  - Goodbye, stockholders. Select Medical to go private, avoiding scrutiny over
      admission policy changes.

PMID- 15554010
TI  - Public scrutiny. State officials hunt for fraud by health insurers.

PMID- 15554011
TI  - The choice. Debates reveal philosophical chasm between Bush, Kerry healthcare
      plans.

PMID- 15554012
TI  - State of the ballot battles. Medical liability reform, funds to support
      children's hospitals, ER services and stem-cell research among measures in
      voters' hands.

PMID- 15554013
TI  - Beating strongly. All cardiac hospitals are reporting better outcomes, but
      Solucient's 100 top facilities are setting the bar for quality of care.

PMID- 15554014
TI  - IT IQ in varying degrees. Growing number of universities offering executives
      intensive education, distance learning in field of biomedical informatics.

PMID- 15554015
TI  - [Diabetes mellitus, left ventricular dysfunction and congestive heart failure].
AB  - Diabetes is a well known risk factor for the development of congestive heart
      failure. Epidemiological evidence in the community underscores the prevalence of
      left ventricular systolic dysfunction in diabetic patients as 2-fold with respect
      to non-diabetic ones, with half of them completely asymptomatic. Diastolic
      dysfunction in diabetic hearts, in comparison with non-diabetic, is even more
      frequent. The high prevalence has been explained by the frequent coexistence of
      an underlying diabetic cardiomyopathy, hypertension and ischemic heart disease.
      In these patients, the diabetic metabolic derangement, together with the early
      activation of sympathetic nervous system, induce a decrease of myocardial
      function. The activation of renin-angiotensin system results in an unfavorable
      cardiac remodeling. The progression from myocardial damage to overt dysfunction
      and heart failure is often asymptomatic for a long time and frequently
      undiagnosed and untreated. Currently, the widespread availability of
      echocardiography and possibly the use of cardiac natriuretic peptides, may allow
      for an earlier recognition of most of such patients. In heart failure, diabetic
      patients have a worse prognosis than non-diabetics. The available pharmacological
      treatments, such as ACE-inhibitors, beta-blockers and possibly angiotensin
      receptor blockers, togheter with a tight glycemic control, may be effective to
      reverse the remodeling process and prevent cardiovascular events. In order to
      identify most of the diabetic patients at risk of development of left ventricular
      dysfunction and to prevent its progression to overt heart failure, it seems
      important to elaborate a screening strategy in order to diagnose and treat most
      of diabetic patients with myocardial damage.

PMID- 15554016
TI  - [New devices for the invasive treatment of acute myocardial infarction].
AB  - Primary angioplasty has been demonstrated to be the best reperfusion therapy in
      patients with acute myocardial infarction. Anyway, its efficacy is reduced by the
      distal embolization, above all in the setting of acute myocardial infarction. In
      the last years, many devices have been designed in order to limit this
      complication which may lead to a poor prognosis. This review will focus on the
      different devices of thrombectomy and distal protection, until now available in a
      cath lab.

PMID- 15554017
TI  - [Does a "senile heart" actually exist?].
AB  - The study of the aging heart raised for a long time difficulties in
      distinguishing the age-related physiological processes from the associated
      pathological changes. In recent years, however, several obscure or controversial
      items have been clarified through a wide use of imaging techniques such as
      echocardiography, positron emission tomography, and of molecular biology. The
      general notion of remodeling has been extended to include the arterial
      capacitance vessels, and the emerging concept of "ventricular-arterial coupling"
      has yielded a rational explanation for some structural and functional changes of
      the aging heart. Particular attention has been paid to the left ventricular
      diastolic dysfunction, while the new data have generally confirmed the old ones
      regarding the preserved systolic performance at rest. The aging of the heart
      should anyhow be considered in the context of the "cardiopulmonary unit" and by
      the light of the new acquisitions on the loss of skeletal muscle mass and
      strength (sarcopenia).

PMID- 15554018
TI  - [Potential impact of drug-eluting stents in Sicily: results from a multicenter
      survey and cost-benefit analysis of drug-eluting stents versus bare metal
      stents].
AB  - BACKGROUND: The recent introduction of drug-eluting stents (DES) has shown, in
      randomized controlled trials, to reduce the incidence of restenosis as compared
      to bare metal stents (BMS). Since their cost is considerably higher than that of
      BMS, the study assessed the economic impact of the adoption of this new therapy
      in the Sicilian clinical practice. METHODS: An economic evaluation was carried
      out by means of a linear decision model developed in Excel that simulated and
      compared costs and clinical pathway, within 1 year of the intervention, of
      hypothetical groups of patients with de novo lesions undergoing angioplasty with
      DES or BMS. Clinical data were obtained from the available literature and adapted
      to the Sicilian reality, using data from an original survey conducted in 7 local
      cath labs. The survey collected information on the anatomical case-mix of the
      population treated, the average number of stents used in the various procedures
      and the methods of treatment for in-stent restenosis. RESULTS: Compared to BMS,
      DES allows to avoid, on average, 11.8 revascularizations out of 100 patients over
      a period of 1 year, but requires to bear an incremental net cost of Euro 931 for
      the annual treatment of each patient. The cost-benefit ratio is more favorable
      for those categories of patients/lesions in which the risk of in-stent restenosis
      is higher and, at the same time, the number of stents implanted per procedure is
      lower (single-vessel diabetics and small vessels). CONCLUSIONS: The results of
      the study show how, within the scope of a policy that has tended more and more to
      rationalize the use of available health resources, the use of the expensive DES
      is not justified from an economic point of view in groups of patients and types
      of lesions in which a BMS is also associated with a lower likelihood of
      revascularization. Therefore, the study provides a starting point for
      consideration by hospital centers, suggesting the use of a mixture of DES for the
      treatment of lesions/patients at the highest risk of restenosis and BMS for the
      treatment of lesions/patients at lower risk of re-intervention.

PMID- 15554019
TI  - [Reduction of radiological exposure time during radiofrequency catheter ablation
      procedures using a novel intracardiac localization system based on the Ohm's
      law].
AB  - BACKGROUND: Three-dimensional nonfluoroscopic system may be helpful to guide
      radiofrequency catheter ablation procedures and to reduce the radiological
      exposure. A new intracardiac navigation and multicatheter visualization system
      based on Ohm's law (LocaLisa, Medtronic, Minneapolis, MN, USA) has been recently
      introduced. The aim of our study was to assess the efficacy of the Loca-Lisa
      system in comparison to fluoroscopy-based approach in reducing the radiological
      exposure time required for radiofrequency catheter ablation procedures. METHODS:
      One hundred and thirty-seven consecutive patients underwent LocaLisa-based
      radiofrequency catheter ablation procedures in our cardiac electrophysiology
      laboratory during 19 months of LocaLisa utilization (from October 2001 to April
      2003): 46 atrial flutter, 44 atrioventricular node reentrant tachycardia, 16
      atrioventricular reentry tachycardia due to atrioventricular accessory pathway,
      14 atrial fibrillation, 11 ectopic atrial tachycardia, and 6 atrioventricular
      node modulation. We retrospectively compared the radiological exposure times of
      this group of patients to those of the last 137 patients undergone fluoroscopy
      based radiofrequency catheter ablation procedures for curing the same index
      arrhythmia by the same procedural protocol. RESULTS: The mean radiological
      exposure time was significantly shorter for the LocaLisa-based radiofrequency
      catheter ablation procedures (16 +/- 12 vs 34 +/- 17 min; reduction of 53%, p <
      0.01) and it occurred for all the arrhythmia types. The reduction was of 64%
      (from 39 +/- 18 to 14 +/- 12 min, p < 0.01) for atrial flutter, 42% (from 24 +/-
      10 to 14 +/- 11 min, p < 0.01) for atrioventricular nodal reentrant tachycardia,
      30% (from 40 +/- 14 to 28 +/- 14 min, p = 0.02) for atrioventricular reentry
      tachycardia, 57% (from 49 +/- 12 to 21 +/- 13 min, p < 0.01) for atrial
      fibrillation (right atrial linear lesions), 50% (from 38 +/- 12 to 19 +/- 8 min,
      p < 0.01) for ectopic atrial tachycardia and 42% (from 12 +/- 11 to 7 +/- 5 min,
      p = NS) for atrioventricular node modulation. The reduction in the radiological
      exposure time progressively increased as our team got used with the
      nonfluoroscopic navigation system. CONCLUSIONS: Overall and single arrhythmia
      divided mean radiological exposure times can be significantly reduced by the
      LocaLisa system during radiofrequency catheter ablation procedures. The reduction
      of radiation increases progressively by becoming friendly to the system with a
      very short duration of learning curve phase.

PMID- 15554020
TI  - [Prevalence of cardiovascular manifestations in Marfan syndrome].
AB  - BACKGROUND: Marfan syndrome is an inherited connective tissue disorder with an
      autosomic dominant transmission. The prevalence is 1:5000-10 000 and the clinical
      major criteria involve the skeletal and ocular apparatus and the cardiovascular
      and central nervous system. The main cause of morbidity is represented by the
      thoracic aortic dissection/aneurysm that is responsible for 80% of the deaths.
      METHODS: We performed a clinical study on 227 patients enrolled at our Clinical
      and Research Marfan and Related Disorders Center. The aim of this study was to
      describe the prevalence of cardiovascular manifestation in this cohort of
      patients. RESULTS: Aortic dilation was present in 172 patients (75.8%), mitral
      valve prolapse in 179 (78.9%). Aortic insufficiency was present in 83 patients
      (36.6%), mitral insufficiency in 165 (72.7%). When analyzed separately, in < 10
      year and > 40-year patients aortic dilation was more prevalent than mitral valve
      prolapse. Three patients presented with interatrial septal defect, 4 aortic
      bicuspid valve; 23 had a history of ventricular and supraventricular arrhythmias,
      and in 2 patients an implantable cardioverter device had been implanted. Fifty
      seven patients were treated with beta-blockers and 28 had been operated for
      aortic aneurysmal dilation. CONCLUSIONS: In Marfan syndrome mitral valve prolapse
      and aortic dilation are the main cardiovascular manifestations, interatrial
      septal defect and aortic bicuspid valve had the same prevalence than in subjects
      without Marfan syndrome. These data refer to our first patient evaluation;
      further studies are needed to evaluate the progression and the natural history of
      cardiovascular manifestations in Marfan syndrome.

PMID- 15554021
TI  - [The risk of noncardiac surgery in patients with heart disease: a new way for an
      easy approach to a right preoperative assessment].
AB  - The aim of cardiovascular preoperative evaluation in noncardiac surgery is to
      assess the current cardiovascular status of patients, to find underlying unknown
      diseases, to advise about medical management for patients in the preoperative
      period and, eventually, to postpone noncardiac surgery until cardiac conditions
      are improved or stabilized. The basic clinical evaluation, obtained by history,
      physical and ECG examination, provides enough data to estimate the cardiovascular
      risk. Cardiovascular risk factors and specific surgery risk have a huge
      importance in this evaluation; the specific surgery risk can be classified into
      three categories: high, intermediate, and low. However, the evaluation of cardiac
      risk is not simple and the eventual legal consequences are important. For this
      reason we propose this hypothesis for an easy approach to a right preoperative
      assessment based on a succession of eight steps; this way would be a support for
      specialists and young physicians that are called to give a clinical report on
      surgery timing and on possible problems of patients with cardiovascular disease
      undergoing noncardiac surgery.

PMID- 15554022
TI  - [Evidence-based medicine and cardiovascular risk stratification aimed to drug
      reimbursement: uselessness of risk charts].

PMID- 15554024
TI  - [DES (i.e. don't exaggerate the story)].

PMID- 15554023
TI  - [A rare cardiac tumor: the malignant fibrous histiocytoma. Description of a
      case].
AB  - The present report describes the case of a 61-year-old woman with malignant
      fibrous histiocytoma of the left atrium originating from the left atrial free
      wall, operated on in emergency for a suspected large left atrial myxoma that, at
      the echo scan, was consistently protruding through the left atrioventricular
      orifice at each diastole and was almost completely occluding the left ventricular
      inflow, causing signs of congestive heart failure and severe dyspnea. Surgery was
      performed as radically as possible, but the histological examination of the
      specimen revealed the exact diagnosis of the neoplasm. About 75% of primary
      tumors are benign and 75% of these are atrial myxomas. The malignant tumors
      consist of various sarcomas: myxosarcoma, liposarcoma, angiosarcoma,
      fibrosarcoma, leiomyosarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma,
      undifferentiated sarcoma, reticulum cell sarcoma, neurofibrosarcoma, and
      malignant fibrous histiocytoma. The long-term results for sarcomas are very poor
      and there are few survivors after several months from surgery due to the extent
      of local spread and invasion or because of the frequent distant metastases.
      Malignant fibrous histiocytoma constitutes about 2% of all cardiac malignancies,
      which might grow within several localized areas, occasionally in the heart.
      Echocardiography represents the best examination procedure for both diagnosis and
      follow-up of patients with cardiac tumors.

PMID- 15554025
TI  - [One adjective, three thoughts].

PMID- 15554026
TI  - Statins and stroke prevention: focus on women.

PMID- 15554027
TI  - Coronary microvascular dysfunction and ischemia in hypertrophic cardiomyopathy.
      Mechanisms and clinical consequences.
AB  - Symptoms and signs of myocardial ischemia are often found in patients with
      hypertrophic cardiomyopathy (HCM) despite angiographically normal coronary
      arteries. Myocardial ischemia is deemed responsible for some of the lethal
      complications of HCM including ventricular arrhythmias, sudden death, progressive
      left ventricular remodeling, and systolic dysfunction. In the past decade, a
      number of studies using positron emission tomography have demonstrated severe
      impairment of the vasodilator response to dipyridamole in the majority of HCM
      patients, not only in the hypertrophied septum but also in the non-hypertrophied
      left ventricular free wall. In the absence of coronary stenoses, this finding is
      indicative of diffuse microvascular dysfunction, in line with the autoptic
      evidence of widespread abnormalities of the intramural coronary arterioles. In
      turn, microvascular dysfunction represents a very likely substrate for recurrent
      ischemia. This may account for the fact that microvascular dysfunction has
      recently been shown to represent an early and powerful predictor of an
      unfavorable outcome in HCM. The aim of this article is to provide a concise
      overview of the available evidence of microvascular dysfunction and ischemia in
      HCM, and to speculate on the potential implications for management.

PMID- 15554028
TI  - Diagnostic management of patients with palpitations of unknown origin.
AB  - The first-line investigations in the diagnostic management of patients with
      palpitations include history taking, physical examination and ECG. These
      investigations yield a definitive or probable diagnosis in a good proportion of
      patients. If the patient is suffering from heart disease, or if the palpitations
      are frequent or poorly tolerated, ambulatory ECG monitoring and
      electrophysiological study should be undertaken. Holter monitoring (useful when
      symptoms occur daily) has a rather low sensitivity, while event recorders (useful
      in compliant patients with infrequent palpitations that are fairly long-lasting)
      and external loop recorders (recommended in cases of infrequent short-lasting
      palpitations associated with hemodynamic impairment) have proved to have a higher
      sensitivity. The diagnostic yield of the electrophysiological study (generally
      recommended when the recording attempts using ambulatory ECG monitoring fail to
      provide a diagnosis) depends on the stimulation protocol used, the clinical
      characteristics of the patients studied, and the type of arrhythmias induced.
      Implantable loop recorders may be recommended in patients with rare, highly
      symptomatic palpitations associated or not with hemodynamic impairment, when the
      other diagnostic modalities prove to be inconclusive.

PMID- 15554029
TI  - The ALPHA study (T-wave alternans in patients with heart failure): rationale,
      design and endpoints.
AB  - BACKGROUND: Sudden death and pump failure are the main causes of death in
      patients with heart failure. Patients with ischemic and non-ischemic
      cardiomyopathy are at similar risk of arrhythmic mortality; however, standard non
      invasive and invasive tests are not routinely available for non-ischemic
      patients. T-wave alternans (TWA) has been proposed as a potential marker of
      susceptibility to ventricular tachycardia-fibrillation in several groups of
      patients. METHODS: The ALPHA study was designed to evaluate the independent
      predictive value of the measurement of microvolt TWA on the combined occurrence,
      after 18 months of follow-up, of cardiac death and life-threatening arrhythmias
      in a population of patients with non-ischemic dilated cardiomyopathy and NYHA
      class II and III. This is a multicenter prospective observational study. A total
      of 370 patients, with measurable TWA, will be enrolled during routine follow-up
      for heart failure treatment; a logbook will be used to collect basic information
      on the whole screened population. Patients will be enrolled during a 2-year
      period and will be followed up for 18 months. The primary endpoint of the study
      will be the combined incidence of cardiac death and life-threatening ventricular
      arrhythmias. The study will complete recruitment by mid 2004 and report in 2006.

PMID- 15554030
TI  - Idiopathic dilated cardiomyopathy: prognostic significance of
      electrocardiographic and electrophysiologic findings in the nineties.
AB  - BACKGROUND: With the exception of a few cases such as aborted sudden cardiac
      death, sustained ventricular tachycardia, and syncope of unexplained origin,
      there is no consensus on the clinical findings identifying patients with
      idiopathic dilated cardiomyopathy with an increased risk of sudden cardiac death
      or malignant ventricular arrhythmias. METHODS: To verify whether
      electrocardiographic and arrhythmologic features could be useful for prognostic
      stratification, 78 consecutive patients with an invasive diagnosis of idiopathic
      dilated cardiomyopathy, but without symptomatic ventricular arrhythmias, were
      enrolled in a prospective study. Signal-averaged ECG, 24 to 48 hour ECG
      monitoring and electrophysiologic study were performed at the time of diagnosis
      to identify arrhythmogenic predictors of outcome. Transplant-free and arrhythmic
      event-free survival was evaluated on the basis of initial parameters. RESULTS:
      During a mean follow-up of 85 months, 9 patients died (6 of sudden cardiac death
      and 3 of congestive heart failure), 10 patients underwent cardiac transplantation
      for refractory heart failure, and 3 presented with sustained ventricular
      tachycardia. The independent predictors for death and cardiac transplantation
      were an HV interval > 55 ms and the combination of frequent repetitive
      ventricular ectopics with a poor left ventricular function. A strong index of
      arrhythmic events proved to be the association of a prolonged HV interval with a
      wide (> 110 ms) QRS complex (odds ratio 4.53, 95% confidence interval 1.57-13.04,
      p < 0.005). CONCLUSIONS: An accurate measurement of the HV interval and QRS
      duration at baseline evaluation may add prognostic information in patients with
      idiopathic dilated cardiomyopathy. In our experience, abnormal values of both
      parameters identified a group of patients with a very high risk of late occurring
      arrhythmic events.

PMID- 15554031
TI  - Determinants of early-onset cardiovascular disease: a case-control study of young
      myocardial infarction patients.
AB  - BACKGROUND: The present case-control investigation was undertaken with the aim of
      thoroughly assessing the risk profile of young coronary patients and to correlate
      it with their endothelium-dependent vasodilation and with the presence of
      atherosclerotic lesions. METHODS: Forty-eight subjects (age < 41 years) diagnosed
      with myocardial infarction were screened. They were matched 1:1, for age and sex,
      with controls. We evaluated the serum total, HDL-, and LDL-cholesterol,
      triacylglycerols, fibrinogen, homocysteine, folic acid, vitamin B12, vitamin E,
      antioxidant capacity, and uric acid levels, and we also analyzed the patients for
      the presence of Helicobacter pylori and of methylenetetrahydrofolate reductase
      and cystathionine beta-synthase genetic mutations. Post-ischemic vasodilation of
      the brachial artery was evaluated and the intima-media thickness of the carotid
      arteries was measured at echo-Doppler. RESULTS: A statistical modeling selection
      between block variables revealed that smoking, the apoepsilon genotype,
      dyslipidemia, fibrinogen, vitamin E concentrations, and intima-media thickness
      were important predictors of cardiovascular disease, with an accuracy of 91.7%.
      CONCLUSIONS: On the basis of these results, we believe that acute coronary events
      in young subjects should be followed by a screening of their siblings, as they
      might be at higher risk for cardiovascular disease.

PMID- 15554032
TI  - Mechanisms and predictors of transient left ventricular dysfunction early after
      successful percutaneous balloon mitral valvuloplasty.
AB  - BACKGROUND: The immediate effects of balloon mitral valvuloplasty (BMV) on left
      ventricular (LV) function in patients with mitral stenosis are still
      controversial. The aim of this study was to investigate the mechanisms and
      potential clinical, echocardiographic and hemodynamic predictors of transient LV
      dysfunction occurring in patients with mitral stenosis early after successful
      percutaneous BMV. METHODS: Sixty patients without residual mitral regurgitation
      were divided into two groups according to the changes in the left atrial (LA)
      pressure 15 min after successful BMV: 18 patients (group A) did not present with
      any reduction in LA pressure, and underwent nitroglycerin administration (0.4 mg,
      sublingually). The remaining 42 patients (group B) presented with a decrease in
      LA pressure. RESULTS: At baseline, both the mitral valve gradient and area
      assessed at echocardiography and during cardiac catheterization were similar in
      groups A and B. Group A patients presented with, however, higher LV early- and
      end-diastolic pressures and peak V waves during cardiac catheterization both
      prior to and 15 min after BMV than group B patients (all p values < 0.05). In
      group A, nitroglycerin administration was associated with a decrease in LV end
      diastolic pressure (p = 0.049), LA pressure (p < 0.001), and peak V wave (p <
      0.001) that was still persistent 30 min after its administration, reaching values
      similar to those observed in group B early after BMV. At multivariate analysis,
      the only independent predictors of LV dysfunction early after BMV were found to
      be LV early- (p = 0.015) and end-diastolic (p = 0.023) pressures at baseline and
      the Wilkins' score (p = 0.004). CONCLUSIONS: After successful BMV a transient
      lack of LV adaptation to the increased LV preload resulting in a persistently
      elevated LA pressure is predicted by higher baseline LV diastolic filling
      pressures and higher Wilkins' scores. It is promptly and steadily reversed by
      nitroglycerin administration through a transient LV unloading, thus allowing a
      correct hemodynamic evaluation of the immediate results of the procedure.

PMID- 15554033
TI  - Epoprostenol in chronic thromboembolic pulmonary hypertension with distal
      lesions.
AB  - BACKGROUND: Although patients with primary pulmonary hypertension and patients
      with chronic thromboembolic pulmonary hypertension with distal lesions may share
      similar pathophysiological characteristics, scarce information is available on
      the usefulness of epoprostenol in this form of secondary pulmonary hypertension.
      The aim of this study was to evaluate the feasibility, safety and efficacy of
      epoprostenol therapy in surgically untreatable patients with chronic
      thromboembolic pulmonary hypertension. METHODS: Continuous infusive therapy with
      epoprostenol was undertaken in 16 patients with primary pulmonary hypertension
      and in 11 surgically untreatable thromboembolic pulmonary hypertension patients.
      The median follow-up was 12.4 months (range 6-23 months). Patients underwent
      clinical, echocardiographic and hemodynamic evaluation at baseline and a 6-min
      walk test every 3 months after beginning epoprostenol; ultrasound evaluations
      were repeated in a subgroup of patients. RESULTS: Epoprostenol therapy improved
      the clinical status, exercise tolerance and NYHA functional class. A greater left
      ventricular end-diastolic volume was recorded at echocardiography in both groups.
      CONCLUSIONS: Epoprostenol therapy may be feasible, safe and clinically effective
      in patients with surgically untreatable chronic thromboembolic pulmonary
      hypertension.

PMID- 15554034
TI  - Conotruncal heart defects: impact of genetic syndromes on immediate operative
      mortality.
AB  - BACKGROUND: The surgical outcome of conotruncal heart defects in patients with
      genetic syndromes has been poorly studied. The aim of this prospective 5-year
      multicenter study was to elucidate the post-surgical death rate of children with
      conotruncal heart defects in relation to the presence of associated genetic
      syndromes. METHODS: Two institutions enrolled 350 consecutive inpatients with
      conotruncal heart defects, aged between 1 day and 60 months, who were submitted
      to surgery; all patients were evaluated by a clinical geneticist and had a
      standard metaphase chromosome analysis and a fluorescent in situ hybridization
      study searching for deletion of chromosome 22q11 (del22q11). RESULTS: No genetic
      syndrome was diagnosed in 289 patients; among the other 61 patients, 27 had
      DiGeorge velocardiofacial syndrome (del22q11), 16 patients had Down syndrome, and
      18 presented with other genetic syndromes. The overall post-surgical death rate
      was higher in syndromic patients (18%) than in non-syndromic ones (10.7%) with a
      relative risk of 1.9 (p = 0.06). However, children with del22q11 showed a higher
      risk for surgical mortality (25.9 vs 10.7%; relative risk 2.4, p = 0.03).
      Del22q11 was identified as a risk factor for immediate surgical mortality in
      patients with pulmonary atresia and ventricular septal defect and in patients
      with interrupted aortic arch. CONCLUSIONS: Down syndrome is not a risk factor for
      surgery in children with conotruncal heart defects. The presence of a del22q11
      may influence the surgical results in children with pulmonary atresia and
      ventricular septal defect and in those with interrupted aortic arch. Patients
      with genetic syndromes other than del22q11 and Down syndrome have a higher
      surgical mortality compared to that observed in non-syndromic patients. These
      data may be useful for preoperative counseling and for the elaboration of
      specific protocols of perioperative treatment.

PMID- 15554035
TI  - Noninvasive recognition of asymptomatic left anterior descending coronary artery
      stenosis in hypertensive left ventricular hypertrophy by conventional
      transthoracic Doppler echocardiography.
AB  - The noninvasive determination of the blood flow velocity in the left anterior
      descending coronary artery (LAD) at color Doppler echocardiography may provide
      useful clinical information. In this report, the authors describe the case of a
      patient with left ventricular hypertrophy secondary to hypertension in whom a
      critical but asymptomatic LAD stenosis was diagnosed at conventional
      echocardiography without resorting to pharmacological stress.

PMID- 15554036
TI  - Floating thrombus in the thoracic aorta: what should be done?
AB  - Floating thrombus in a non-aneurysmal and non-atherosclerotic thoracic aorta is a
      rare event with potentially catastrophic complications. Especially younger
      patients have a higher risk of embolization. Transesophageal echocardiography is
      the diagnostic method of choice. However, the treatment of this pathology is
      still controversial and includes both medical and surgical options. We report our
      experience with a 43-year-old patient and a review of the literature, and make a
      proposal for therapeutic interventions.

PMID- 15554037
TI  - Transient ballooning of the left ventricle: a case report.
AB  - A 67-year-old woman was admitted to the coronary care unit for chest pain with
      ECG modifications suggestive of acute myocardial infarction. The clinical course
      of the disease and the absence of abnormalities of the epicardial vessels with
      reversible asynergy of the apical segments of the left ventricle were suggestive
      of the syndrome of transient apical ballooning of the left ventricle. To my
      knowledge, this is the first case of the disease described in the Italian
      population.

PMID- 15554038
TI  - Drug-eluting stent implantation in primary angioplasty of an anomalous left main
      coronary artery: diagnostic and technical considerations.
AB  - The presence of an anomalous origin and/or distribution of a coronary artery as
      the infarct-related vessel during primary angioplasty for acute myocardial
      infarction might represent a clinical and technical challenge. We report on a
      case of a patient with an acute anterior myocardial infarction who was referred
      to our hospital for primary angioplasty and whose culprit lesion was located on
      an aberrant left main coronary artery. The purpose of this case report was to
      review the incidence and angiographic evaluation of an anomalous coronary vessel
      and to discuss the technical approach to an anomalous left main intervention and
      its impact on clinical outcome.

PMID- 15554039
TI  - The big story. GP budgets set to take hold, but don't write off PCTs--yet.

PMID- 15554040
TI  - The big story. The impact of primary care-led commissioning and how commissioning
      might best develop in the future.

PMID- 15554041
TI  - The HSJ barometer.

PMID- 15554042
TI  - Clinical management where medicine meets management. More than skin deep.
AB  - Modernisation has brought down outpatient waits and did-not-attends at
      Addenbrooke Hospital's dermatology department. A 360-degree review of services
      has led to continuous service Improvement. GPs and hospital nurses have received
      specialist training, freeing up consultant time and enabling more consultants to
      be seen.

PMID- 15554043
TI  - Medical reservists. The real frontline service.

PMID- 15554044
TI  - Mental Health. Psychiatrist examination.

PMID- 15554045
TI  - HSJ people. Haven't you lot got homes to go to?

PMID- 15554046
TI  - My brilliant career--social care. Point of departure. Interview by Emma Maier.

PMID- 15554047
TI  - Minimal stress.

PMID- 15554048
TI  - Reviewing the concept of Dahl.
AB  - Toothwear may have a multifactorial aetiology but is often localized to the upper
      anterior teeth. This is normally accompanied by a loss of interocclusal space.
      This paper aims to outline the management of localized anterior toothwear. It
      discusses several options available to create space for anterior restoration,
      with particular reference to the use of the 'Dahl' technique. Dahl described a
      non-invasive technique to create increased interocclusal space. The increased
      space eliminates the need for further occlusal reduction during crown preparation
      which is ideal in the worn dentition. This paper illustrates and describes the
      clinical applications of Dahl's original technique.

PMID- 15554049
TI  - Antibiotics in the treatment of periodontitis.
AB  - The emerging worldwide problem of bacterial resistance has resulted from overuse
      and misuse of systemic antibiotics. It is appropriate therefore to review
      periodontal treatment strategies to determine whether systemic antibiotics have a
      role to play in the management of periodontitis. For the great majority of
      patients presenting with periodontal conditions, systemic antibiotics are not
      indicated. Instead, treatment should focus on mechanical disruption of plaque
      biofilms, plaque control and risk factor modification. Systemic antibiotics may
      be indicated in severe spreading infections, some aggressive forms of
      periodontitis, and necrotizing periodontal conditions. These conditions present
      infrequently in general practice, most will require referral to a periodontal
      specialist and the decision to use systemic antimicrobials as part of periodontal
      management is more appropriately taken within a specialist centre. Systemic
      antibiotics are not indicated in the vast majority of periodontal conditions
      encountered in general dental practice.

PMID- 15554050
TI  - Providing a numerical measure of oral health--can it be done and how accurate is
      it?
AB  - An Index of Oral Health (OHX) was developed by Burke and Wilson in the mid 90s.
      Use of the index involves assessing patient comfort and satisfaction in addition
      to the assessment of caries, periodontal disease, toothwear, mucosa, occlusion
      and dentures, where appropriate. On completion of this structured examination,
      the clinician arrives at an overall oral health index (OHX) for the patient,
      which is expressed as a fraction of the maximum achievable score. The index was
      modified by Denplan UK by amending the calculations to produce the Oral Health
      Score (OHS). The Reproducibility of the OHX and OHS was tested at Birmingham
      Dental Hospital and School during 2001 and 2002 and was found to be satisfactory.
      The dentists' opinions on the OHX and OHS were assessed by means of
      questionnaires. Most of the dentists felt that both were easy to use.

PMID- 15554051
TI  - Advances in fixed appliance orthodontics.
AB  - In 1992, Postlethwaite wrote an article for Dental Update entitled 'Advances in
      fixed appliance design and use'. In the subsequent years there have been, as in
      most dental specialties, huge advances in materials. These have resulted in
      improved efficiency, convenience and simplicity in using fixed appliance
      orthodontics. This article is intended to be an update in these advances over the
      last 10 years.

PMID- 15554052
TI  - Mentoring and personal development planning in postgraduate dental education: a
      review.
AB  - Mentoring and Personal Development Plans (PDPs) are educational tools that have
      been piloted in postgraduate medical education in recent years. Along with
      another educational tool, performance appraisal, they have been introduced
      nationally as part of the recent General Medical Practitioner contract of April
      2003. In the light of the compulsory Continuing Professional Development and
      Lifelong Learning Schemes introduced recently by the General Dental Council for
      all dentists, mentoring and PDPs will surely have important roles to play in
      postgraduate dental education in the future. This article reviews the roles that
      mentoring and PDPs have played in postgraduate education recently.

PMID- 15554053
TI  - Indirect aesthetic adhesive restoration with fibre-reinforced composite resin.
AB  - This paper describes the restoration of an endodontically treated upper first
      molar with a fibre-reinforced onlay indirect composite resin restoration. The
      clinical and radiographic examination confirmed that the tooth had suffered
      considerable loss of structure. Therefore, an indirect restoration was indicated.
      First, a core was built with resin-modified glass ionomer cement, followed by
      onlay preparation, mechanical/chemical gingival retraction and impression with
      addition-cured silicone. After the laboratory phase, the onlay was tried in,
      followed by adhesive bonding and occlusal adjustment. It can be concluded that
      fibre-reinforced aesthetic indirect composite resin restoration represented, in
      the present clinical case, an aesthetic and conservative treatment option.
      However, the use of fibres should be more extensively studied to verify the real
      improvement in physical and mechanical properties.

PMID- 15554054
TI  - Mental nerve anaesthesia; a complication of sickle cell crisis during childbirth.
AB  - This report describes the case of an Afro-Caribbean lady diagnosed with sickle
      cell anaemia, who presented with permanent mental nerve anaesthesia as a result
      of a sickle cell crisis during childbirth.

PMID- 15554055
TI  - An update on psychiatric disorders in relation to dental treatment.
AB  - Psychiatric disorders like depression and anxiety are commonly encountered in
      patients presenting to dental practitioners. The symptoms at presentation may not
      always be straightforward and, if not suspected and specifically explored, can
      often be missed. If unrecognized and hence subsequently untreated, this can have
      numerous adverse consequences to the patient and the health service. Hence, it is
      important that dental practitioners are more aware of the varying presentations,
      assessment and management of psychiatric disorders in their patients. In this
      paper, we focus on description of the common psychiatric disorders and their
      assessment from a dental practitioner's perspective. There is clearly a need for
      greater collaboration between dental practitioners and psychiatrists.

PMID- 15554056
TI  - Physical signs for the General Dental Practitioner. Case 18.

PMID- 15554057
TI  - Assignment of fourteen microsatellite markers to the chicken linkage map.
AB  - A large mapping population, with 874 F2 individuals, was generated by
      reciprocally intercrossing 2 chicken lines. A genetic map of 2,426.6 cM
      comprising 25 linkage groups was established based on 145 microsatellite markers.
      Chromosome locations were assigned for 14 previously unmapped markers. The marker
      ADL0132 was previously mapped to chromosome 9; however, here close linkage to the
      MCW0091 marker on chromosome 4 was found. With this exception, the derived
      linkage map was in excellent agreement with the chicken consensus map. A
      comparison with the chicken genome assembly (http://genome.ucsc.edu; February
      2004) suggested a few minor errors in the assembly. A PCR-RFLP test was used to
      genotype a single nucleotide polymorphism in the melanocortin receptor 3 (MC3R)
      gene in the intercross, and pyrosequencing was used to map the genes for
      Hemopoetic Cell Kinase (HCK) and Bone Morphogenic Protein 7 (BMP7). The HCK and
      BMP7 genes on linkage group E32 showed significant linkage to MC3R on the distal
      end of linkage group E47W24, consequently joining the 2 linkage groups. A
      comparison between the linkage data in the current study and the physical
      location of markers as revealed in the chicken genome sequence assembly (February
      2004) showed a 3-fold higher recombination rate on microchromosomes than on
      macrochromosomes.

PMID- 15554058
TI  - Cloning and expression of Tsaiya duck liver fatty acid binding protein.
AB  - Liver basic fatty acid (FA)-binding protein (Lb-FABP) cDNA was cloned from the
      livers of laying Tsaiya ducks and used to generate probes for quantification of
      the Lb-FABP mRNA in Tsaiya ducks. The full-length Lb-FABP cDNA of the Tsaiya duck
      was highly homologous with that of the mallard (99%), chicken (88%), and iguana
      (73%). The amino acid sequence was also highly homologous to Lb-FABP found in
      birds and reptiles, indicating a similar function of the Tsaiya duck Lb-FABP to
      those species. The calculated molecular weight for the cloned duck Lb-FABP was
      14,043g/mol. The Lb-FABP was highly expressed in the liver of laying Tsaiya ducks
      and not detectable in heart, ovary, intestine, or adipose tissues. The expression
      of Tsaiya duck Lb-FABP in the skeletal muscle was also detected, and the sequence
      was confirmed. The greater expression of the hepatic Lb-FABP in the egg-laying
      Tsaiya ducks than the prelaying ducks paralleled the higher FA use by the laying
      ducks. These results suggest that hepatic Lb-FABP may be needed for egg
      production when FA metabolism is high for the ducks. Feeding laying Tsaiya ducks
      with diets enriched with 2% docosahexaenoic acid (DHA) oil for 2 wk significantly
      increased hepatic DHA content compared with in ducks fed a 2% butter basal diet.
      There was no effect of dietary DHA enrichment on the expression of Lb-FABP in the
      liver of Tsaiya ducks. The results suggest that even though the Lb-FABP may be
      involved in hepatic FA metabolism, the effect of individual FA on liver Lb-FABP
      in laying Tsaiya ducks needs to be further studied.

PMID- 15554059
TI  - Efficacy of silymarin-phospholipid complex in reducing the toxicity of aflatoxin
      B1 in broiler chicks.
AB  - Silymarin, the standardized extract of Silybum marianum, is used as a
      hepatoprotector in man, and is a potent antihepatotoxic agent. This study focused
      on the effects of a silymarin-phospholipid complex in reducing the toxic effects
      of aflatoxin B1 (AFB1) in broiler chickens. Twenty-one 14-d-old male commercial
      broilers were randomly allotted to 3 groups and treated as follows: basal diet
      alone [Group C (Control)]; AFB1 at 0.8 mg/kg of feed [Group B1]; AFB1 at 0.8
      mg/kg of feed plus silymarin phytosome, a silymarin complexed form with
      phospholipids from soy, at 600 mg/kg of BW [Group B1+Sil]. Considering the whole
      growth cycle, BW gain and feed intake were lower in AFB1-treated birds with
      respect to controls (P < 0.05). In the B1+Sil group, BW gain and feed intake were
      higher with respect to birds receiving AFB1 alone (P < 0.05), and not different
      from the control birds. Serum biochemistry showed no difference among groups,
      except for a decrease of alanine amino transferase (ALT) in chicks treated only
      with AFB1. Alanine amino transferase activity in AFB1 plus silymarin phytosome
      treated birds was not different from the controls. No treatment differences were
      noted on liver weight. In conclusion, our results suggest that silymarin
      phytosome can provide protection against the negative effects of AFB1 on
      performance of broiler chicks.

PMID- 15554060
TI  - Testing the efficacy of fermented wheat germ extract against Mycoplasma
      gallisepticum infection of chickens.
AB  - The effect of fermented wheat germ extract (FWGE, Immunovet-HBM) was studied in
      chickens challenged with Mycoplasma gallisepticum. Ninety M. gallisepticum- and
      M. synoviae-free 3-wk-old chickens were exposed to aerosol infection of M.
      gallisepticum. One group (30 birds) was treated with FWGE, a second group with
      tiamulin, and a third group was untreated. The fourth group was exposed to PBS
      aerosol as a negative control. On d 9, all chickens were slaughtered and examined
      for the presence of gross and histological lesions, the presence of the challenge
      strain in the organs and specific antibodies in the serum. Body weight gains and
      feed conversion rates were recorded. In the groups treated with FWGE and with
      tiamulin, the chickens remained clinically healthy: their BW gains were 441.7 g
      and 446.8 g, respectively. Feed conversion ratios were 1.72 and 1.71 for FWGE-
      and tiamulin-treated birds, respectively. Control birds had BW gain of 480.8 g,
      and feed conversion ratio of 1.78. The numbers of birds with gross lesions (15
      and 11, respectively) and lesion scores (25 and 25, respectively) of the FWGE-
      and tiamulin-treated groups were significantly lower than in the infected
      untreated group (25 birds, lesion score of 190). No mycoplasma was reisolated
      from brain, liver, spleen, heart, or kidneys of the FWGE-treated birds, and the
      number of mycoplasma isolations from the respiratory tract samples was less
      frequent (10) than from the infected untreated group (64). In addition, 35
      samples from other internal organs were also positive. Twenty percent of the
      birds treated with FWGE showed serological response with a 5.0% reaction score,
      whereas in the infected untreated group, 83.3% of birds were reactors, with a
      62.5% reaction score.

PMID- 15554061
TI  - Effects of feeding blends of grains naturally contaminated with Fusarium
      mycotoxins on performance and metabolism of laying hens.
AB  - An experiment was conducted to evaluate the effects of feeding laying hens grains
      naturally contaminated with a combination of Fusarium mycotoxins. Parameters
      measured included performance, organ weights, and plasma chemistry. One hundred
      and forty-four, 45-wk-old laying hens were fed diets including: (1) control, (2)
      contaminated grains, and (3) contaminated grains + 0.2% polymeric glucomannan
      mycotoxin adsorbent (GMA) for a 12-wk period. The feeding of contaminated grains
      decreased feed consumption compared with controls in the first 4 wk. Feed
      consumption increased, however, from 4 to 8 wk and from 8 to 12 wk. The
      efficiency of feed utilization (feed consumption/egg mass) decreased compared
      with controls in the periods from 4 to 8 and from 8 to 12 wk when birds were fed
      contaminated grains. Supplementation with GMA decreased feed consumption and
      increased the efficiency of feed utilization in the period from 8 to 12 wk. Egg
      production and egg mass decreased in wk 4 and 8 compared with controls when
      contaminated grains were fed, whereas egg and eggshell weights decreased in the
      fourth wk. Plasma uric acid concentrations increased throughout the experiment
      and relative kidney weights increased at the end of the experiment compared with
      controls when birds were fed contaminated grains. The feeding of GMA prevented
      the elevation in uric acid concentrations and relative kidney weights. It was
      concluded that layer performance and metabolism were adversely affected by
      chronic feeding of a combination of Fusarium mycotoxins, and that GMA prevented
      many of these effects.

PMID- 15554062
TI  - Utilization of the nitrate reductase enzymatic pathway to reduce enteric
      pathogens in chickens.
AB  - Previous reports have shown that some bacteria, including Salmonella, use a
      dissimilatory nitrate reductase enzyme pathway (NREP) in anaerobic environments.
      This enzyme reduces nitrate to nitrite and has been shown to cometabolize
      chlorate to cytotoxic chlorite. The present investigations were performed to
      evaluate the susceptibility of a competitive exclusion culture (CE) to the
      experimental chlorate product (ECP). A commercially available CE product was
      evaluated for its nitrate reductase activity and therefore its chlorate
      sensitivity. Individual isolates (in triplicate) were cultured in 10 mL of Viande
      Levure broth containing 5 mM sodium nitrate or 10 mM sodium chlorate. Bacterial
      growth (optical density at 625 nm) was measured and 1-mL aliquots were removed
      concurrently for colorimetric determination of nitrate content at 0, 3, 6, and 24
      h. Of the 15 different facultative strains, 11 had slight NREP utilization, 3 had
      moderate NREP utilization, and the remainder were NREP negative (with slight and
      moderate NREP utilization: >0.1 to <1.0 mM and >1.0 mM nitrate used within 6 h,
      respectively). Of the obligate anaerobes evaluated, 3 had slight NREP utilization
      and the remainder were NREP negative. In vivo studies utilizing both products (CE
      and ECP) in a horizontal transmission challenge model (seeders + contacts) showed
      significant reductions in Salmonella from 5.37 to 1.76 log10 cfu/g and 3.94 to
      0.07 log10 cfu/g, respectively. The combined effect of the CE culture and an ECP
      are effective in killing these food-borne pathogens.

PMID- 15554063
TI  - Effect of strain, feed allocation program, and age at photostimulation on
      reproductive development and carcass characteristics of broiler breeder hens.
AB  - A study was conducted with broiler breeder pullets to investigate the effects of
      strain, age at photostimulation (PS), and release from feed restriction at PS on
      age, BW, ovarian morphology, and carcass characteristics at sexual maturity
      (point of initiation of lay). Sixty birds of each of 4 strains were used. The 4
      types represented a classic strain (A), 2 high-yield strains (B, C), and a
      roaster strain (D). Photostimulation (8L:16D to 14L:10D) was applied at 2
      different ages (21 and 24 wk) to 30 birds of each strain type. Within each of the
      PS periods, 15 birds of each strain were fed ad libitum (F), and the remaining 15
      were feed-restricted (R) following a common feeding schedule. On the day that
      each bird had its first oviposition, its feed was withdrawn. It was euthanized
      the following morning by cervical dislocation and organs were collected. Of the 3
      main effects, feeding program had the greatest effect on all the parameters
      measured. Within the 21-wk PS treatment group, R birds reached onset of sexual
      maturity later than F birds (50.2+/-1.64 vs. 36.6+/-1.01 d, respectively). There
      were no differences in the age at sexual maturity between R and F birds for the
      24-wk PS treatment (28.9+/-0.95 vs. 26.9+/-0.85 for R and F, respectively). These
      results suggest that by 24 wk, all strains had reached a threshold BW and
      responded uniformly to PS regardless of feeding program. Feed restriction reduced
      the number of large yellow follicles (LYF) (diameter >10 mm) (8.43+/-0.23 vs.
      9.65+/-0.33 for R and F birds, respectively). Follicle number was not different
      between birds photostimulated at 21 or 24 wk (9.6+/-0.33 vs. 8.45+/-0.23,
      respectively). Feed restriction affects sexual development that can be modulated
      by the PS program.

PMID- 15554064
TI  - Effects of copper-bearing montmorillonite on growth performance, digestive enzyme
      activities, and intestinal microflora and morphology of male broilers.
AB  - Avian commercial male broiler chicks (n = 240), 1 d of age, were used to
      investigate the effects of copper-bearing montmorillonite (Cu-MMT) on growth
      performance, digestive enzyme activities, and intestinal microflora and
      morphology. The chicks were allocated to 4 treatments, each of which had 5 pens
      of 12 chicks per pen. The 4 treatments were basal diet only (control group),
      basal diet + 1.5 g/kg montmorillonite (MMT), basal diet + 36.75 mg/kg Cu, in the
      form of CuSO4, and basal diet + 1.5 g/kg Cu-MMT. The results showed that
      supplementation with Cu-MMT significantly improved growth performance compared
      with the control diet, and that chicks fed with Cu-MMT had higher average daily
      gain (ADG) than those fed with MMT or CuSO4. Supplementation with Cu-MMT
      significantly reduced the total viable counts of Escherichia coli and Clostridium
      in the small intestine and cecum. Supplementation with MMT or CuSO4 had no
      influence on intestinal microflora. Chicks fed with Cu-MMT had lower viable
      counts of E. coli in cecal contents than those fed with MMT or CuSO4. The
      addition of either MMT or Cu-MMT to the diet improved the activities of total
      protease, amylase, and lipase in the small intestinal contents but had no effect
      on those in the pancreas. Morphological measurements of the small intestinal
      mucosa of chicks indicated that dietary addition of MMT or Cu-MMT improved
      intestinal mucosal morphology.

PMID- 15554065
TI  - Effects of long-term dietary lipids on mature bone mineral content, collagen,
      crosslinks, and prostaglandin E2 production in Japanese quail.
AB  - This study investigated the effects of long-term dietary lipids on mature bone
      mineral content, collagen concentration, crosslink levels, bone marrow and ex
      vivo prostaglandin E2 (PGE2) biosynthesis, as well as the relationship of PGE2
      production to these bone formation parameters. One-month-old male Japanese quail
      were given a basal diet containing 1 of 4 lipid sources: soybean oil (SBO),
      hydrogenated soybean oil (HSBO), chicken fat (CF), or menhaden fish oil (FO) at
      50 g/kg of the diet. At 8 mo of age, lipid treatments did not affect bone length,
      diameter, or weight in quail. Quail fed SBO or CF had significantly lower levels
      of mineral content in tibial bones compared with those given FO. Bone collagen
      level was significantly higher in quail consuming SBO than those given HSBO or
      CF. Collagen crosslink concentration was markedly increased in birds provided FO
      or HSBO compared with those fed SBO or CF. Prostaglandin E2 biosynthesis in bone
      organ culture and marrow were greatly increased in quail maintained on the SBO or
      CF diet compared with those given the FO or HSBO diet. Prostaglandin E2
      production in the bone microenvironment was negatively correlated with tibial ash
      and collagen crosslinks but had a positive correlation with tibial collagen
      levels. These results support our previous findings that long-term exposure to
      diets high in SBO or CF impaired mature bone mechanical properties and
      histological characteristics. Further, the results suggest that long-term
      supplementation of SBO or CF in the diet had a significant adverse effect on
      mature bone metabolism, and that dietary lipids altered bone metabolism, perhaps
      partially by controlling the production of local regulatory factor in bone.

PMID- 15554066
TI  - The impact of prebiotics and salmonellosis on apparent nutrient digestibility and
      Salmonella typhimurium var. Copenhagen excretion in adult pigeons (Columba livia
      domestica).
AB  - The effects of lactose or fructo-oligosaccharide (FOS) supplementation on the
      excretion of salmonellae, apparent digestibilities and excreta consistency were
      studied. Thirty-two male pigeons (Columba livia domestica) were randomly divided
      into 4 equal groups: 3 of 4 groups were orally infected with 10(9) Salmonella
      Typhimurium var. Copenhagen, after being offered a drinking water supplement of
      2% FOS, 2% lactose, or no supplement, respectively, for 2 wk. Pigeons in the
      fourth group were not challenged with S. Typhimurium and remained unsupplemented.
      Initially, FOS increased water intake, resulting in more watery excreta. After
      infection, supplementation showed no major effects on S. Typhimurium excretion,
      nitrogen retention, or apparent nutrient digestibilities, although lactose--and
      to a lesser extent FOS--improved apparent fiber digestibility during recovery
      from the S. Typhimurium infection. The excreta consistency of all pigeons
      returned to normal when recovering from the Salmonella infection. In this trial,
      neither FOS nor lactose was successful in tempering the negative aspects of
      Salmonella infection in pigeons. Nevertheless, it should be stated that future
      investigations should clarify the importance of duration and level of prebiotic
      supplementation and infection level.

PMID- 15554067
TI  - Evaluation of distillers dried grains with solubles as a feed ingredient for
      broilers.
AB  - Two experiments were conducted to evaluate the use of distillers dried grains
      with solubles (DDGS) from modern ethanol plants in broiler diets. Experiment 1
      was a 2 x 2 factorial experiment with diets containing 2 levels of DDGS (0 and
      15%) and 2 diet densities (high and low). The high- and low-density diets were
      formulated to contain 22% CP and 3,050 kcal MEn/kg and 20% CP and 3,000 kcal
      MEn/kg, respectively. Eight pens of 6 chicks were fed an experimental diet from 0
      to 18 d of age. Weight gain and feed efficiency (gain:feed ratio) of the chicks
      receiving the high-density diets were (P < 0.05) better than those of chicks fed
      the low-density diets. However, within the 2 density levels there was no
      difference in performance of chicks fed diets with 0 or 15% DDGS. In experiment
      2, 6 replications of 50 chicks were fed 1 of 4 dietary treatments for 42 d. The
      diets were formulated to be isocaloric and isonitrogenous and contained 0, 6, 12,
      or 18% DDGS. There was no significant difference in performance or carcass yield
      throughout the 42 d experiment except for a depression in BW gain and feed
      conversion when chicks were fed diets with 18% DDGS in the starter period. These
      studies indicate that DDGS from modern ethanol plants is an acceptable feed
      ingredient for broiler diets and can be safely used at 6% in the starter period
      and 12 to 15% in the grower and finisher periods.

PMID- 15554068
TI  - Muscle (pectoralis major) protein turnover in young broiler chickens fed graded
      levels of lysine and crude protein.
AB  - An evaluation of muscle (pectoralis major) protein turnover using the
      phenylalanine flood dose technique was assessed in broiler chicks fed graded
      dietary lysine levels with CP at 170, 210, 250, and 290 g/kg diet. Chicks at 21 d
      old were injected with 1 mL/100 g BW of a phenylalanine solution (120 micromol L
      [ring-2H5)]-phenylalanine). Muscle protein gain was assessed in chicks at 19 and
      23 d of age. No differences were found in weight gain at lysine levels higher
      than 1.22% of the diet. Dietary lysine levels affected fractional synthesis rate
      (FSR, %/ d) of muscle with 170 and 210 g of CP/kg diet but not with 250 and 290 g
      of CP/kg. However, there was increasing FSR with increasing diet lysine levels at
      290 g of CP/ kg. Breast muscle protein deposition (absolute growth rate, AGR,
      mg/d) reached a plateau with 1.22% dietary lysine at CP levels of 170,210, and
      290 g/kg diet, confirming the observation on gross muscle weight. In terms of
      absolute synthesis rate/AGR with minimal absolute breakdown rate (ABR), the diet
      containing 210 g of CP/kg with 1.22% lysine was the most appropriate for chicks
      to 21 d. Levels of lysine influenced protein synthesis more so than protein
      degradation. These data suggest that both protein synthesis and breakdown
      increase at levels of dietary lysine and CP above those required for maximizing
      growth.

PMID- 15554069
TI  - Residual feed intake and its effect on Salmonella enteritidis infection in
      growing layer hens.
AB  - Previous phenotypic selection on residual feed intake (RFI) identified 20
      efficient R- chickens and 20 nonefficient R+ chickens. Residual feed intake was
      defined as the difference between observed feed intake (FI) and expected FI based
      on metabolic BW and BW gain, and was used as a measure for feed efficiency. Body
      weight and BW gain were similar for both groups. Feed intake and RFI were
      significantly higher in R+ birds. It is hypothesized that nonefficient R+ birds
      are more flexible to divert resources from production processes toward
      maintenance processes, thus being better capable of handling a bacterial
      challenge. Chickens of both groups were randomly allocated to immunization with
      heat-inactivated Salmonella enteritidis bacteria, or inoculation with live
      Salmonella bacteria. Transportation to the isolation units caused a decrease in
      FI in R+ birds. This may reflect a particular way of coping with stress in R+
      birds. More R+ birds stopped bacterial shedding considering a nonshedding
      interval of 10 or 11 d (P = 0.041). Nonantigen-specific antibody responses
      against keyhole limpet hemocyanin (KLH) were higher in R- birds. We conclude that
      R+ birds are able to keep their metabolism at a higher level, as indicated by
      higher heart and liver weights, and that Salmonella infection leads to reduced
      heart, liver, and gizzard weights. Oviduct weight and number of small yellow
      follicles were reduced in infected birds. Antigen-specific antibody responses
      were not different between the groups, indicating high priority for this
      parameter as a life trait. Possible differences in stress susceptibility between
      efficient and nonefficient chickens need further examination.

PMID- 15554070
TI  - Intermittent long-term shedding and induction of carrier birds after infection of
      chickens early posthatch with a low or high dose of Salmonella enteritidis.
AB  - Poultry are very likely to become infected with Salmonella in the early posthatch
      period, due to environmental contamination. The purpose of this study was to
      evaluate the effect of infection dose on the risk of persistent infection in
      laying hens. In this study, young layer chicks were orally infected with a low
      (10(2) at 1 d posthatch) or a high dose (10(9) cfu at 1 wk posthatch) of
      Salmonella Enteritidis. The pattern and duration of fecal shedding was studied
      for 18 wk. All chickens shed Salmonella early after infection and shed Salmonella
      intermittently during the whole study period. There were more positive birds in
      the high-dose group than in the low-dose group in the first weeks following
      Salmonella exposure. From 10 wk postinfection onwards, however, birds that were
      orally infected with the low dose of Salmonella Enteritidis shed more Salmonella
      than the birds that received the high dose. At 18 wk of age, there was no
      difference in cecal colonization between the treatment groups. It can be
      concluded that infection of newly hatched chicks with a low dose of Salmonella
      Enteritidis can lead to persistent infection until onset of lay, hereby excreting
      Salmonella bacteria intermittently.

PMID- 15554071
TI  - Aquaporins are observed in the duct epithelia of the epididymal region of the
      large white turkey.
AB  - The cellular and molecular mechanisms regulating the reuptake of the testicular
      fluid supporting sperm exiting the testes in the bird are not known. The presence
      of aquaporins, proteins involved in transmembrane water transport, was
      investigated. Observations were limited to the ductuli efferentes, collecting
      ducts, and ductus epididymis. Interestingly all of these ducts were positive for
      aquaporins-2, -3, and -9 but not aquaporin-7. When positive, aquaporin was
      observed localized over the whole cell or the apical plasma membrane of the
      nonciliated cells and the apical plasma membrane and cilia of the ciliated cells.
      This study is the first to clearly demonstrate the presence of aquaporins-2, -3,
      and -9 in the epididymal region of any bird. We assume the aquaporins play a role
      in concentrating the sperm and in the promotion of sperm maturation in the
      epididymal region.

PMID- 15554072
TI  - Idiopathic pulmonary fibrosis: misunderstandings between epithelial cells and
      fibroblasts?
AB  - Idiopathic pulmonary fibrosis is a complex disease of unknown etiology which
      produces a progressive and irreversible destruction of the alveolar-capillary
      units leading ultimately to death from respiratory failure. For a long time the
      pathogenesis of the disease was attributed to an unresolved chronic alveolitis.
      However, a growing body of evidence suggests that inflammation does not play a
      major role in this disease, and that the pivotal pathogenic mechanisms include
      epithelial cell microinjuries/activation, and fibroblast migration,
      proliferation, and differentiation in myofibroblasts forming discrete foci in the
      injured areas. Active fibroblasts/myofibroblasts from these foci may in turn
      disturb alveolar re-epithelialization, by provoking basement membrane disruption
      and epithelial cell apoptosis finally resulting in exaggerated extracellular
      matrix accumulation. This aberrant repair process annihilates the lung
      architecture leading to the honeycomb remodeling.

PMID- 15554073
TI  - Pulmonary alveolar microlithiasis: report on 576 cases published in the
      literature.
AB  - BACKGROUND AND AIM OF THE WORK: Pulmonary alveolar microlithiasis (PAM) is a rare
      disease characterized by intra-alveolar calcium deposits. The etiology of the
      disease is still unknown and many authors have supposed that an inherited local
      enzymatic defect is responsible for calcium deposition. The present paper aimed
      to study the disorder throughout the world, emphasizing the diagnostic and
      therapeutic views. METHODS: All the papers published on this subject in the
      literature were reviewed. RESULTS: Cases studied were 576 and most of them came
      from Europe (42.7%) and Asia (40.6%). The countries involved were fifty-one and
      twelve of them were attributed with at least ten cases each (Bulgaria, France,
      Germany, India, Italy, Poland, Spain, Russia, Japan, Turkey, USA, ex-Yugoslavia).
      Symptoms were absent in more than half the patients; dyspnoea, cough and chest
      pain were reported in the other cases. Family history for the disease was found
      in one-third of the patients. Chest x-rays and computed tomography were so
      characteristic that they were enough to diagnose the disease even if microscopic
      evidence of the microliths into the alveoli was obtained in most cases (e.g. by
      biopsy, autopsy, bronchoalveolar lavage). Pulmonary tuberculosis or sarcoidosis
      were misdiagnosed in 88 cases out of the 576. The course of the disease was slow
      and patients usually died as a result of cardio-respiratory failure. CONCLUSIONS:
      This review of PAM has shown that the etiology of the disease is still unknown,
      it is widespread throughout the world and easy to diagnose; it develops slowly
      and therapy is ineffective except for lung transplantation.

PMID- 15554074
TI  - Serum protein pattern in sarcoidosis analysed by a proteomics approach.
AB  - BACKGROUND: An altered protein expression in bronchoalveolar lavage fluid (BALF)
      of sarcoidosis patients has previously been reported. As this disease is
      systemic, involving not only the lungs, a change in the serum components is also
      to be expected. In the present study we therefore analysed the total serum
      protein profile of the patients earlier reported, with active sarcoidosis.
      METHODS: We used a proteomics approach to assess overall changes in the protein
      content of serum in patients with acute sarcoidosis (n = 6) compared to healthy
      controls (n = 4). RESULTS: Our results show a significantly higher number of
      protein-spots in serum of the patients compared to the healthy individuals in the
      pH range 4.5-6.7 (median 886 vs. 742, p < 0.05). The total protein concentrations
      of the patients' sera were also significantly higher compared to the controls
      (median 62 vs. 56 mg/mL, p < 0.05). Measurement of the optical densities of the
      protein-spots from two-dimensional electrophoresis gels, covering pH interval 4.5
      6.7, showed varying levels of expression of 22 different serum proteins in the
      patients compared to the controls. These proteins are involved in immune
      responses and some are known markers of inflammation. We found three proteins,
      which were changed concomitantly in the BALF as described in a previous report,
      and sera of the same patients. CONCLUSIONS: Our results are of importance in
      order to identify biochemical markers in blood of sarcoidosis patients. Ideally,
      a combination of markers in BALF and serum may turn out to be disease specific.

PMID- 15554075
TI  - HLA-DR2 predicts susceptibility and disease chronicity in Irish sarcoidosis
      patients.
AB  - BACKGROUND: HLA-DR2 (15) and 14 (6) have been recently proposed as susceptibility
      alleles for the development of sarcoidosis and HLA-DR15 as a marker of poor
      outcome, but validation in other populations is necessary. METHODS: Employing
      serological techniques, we HLA-typed 103 Irish sarcoidosis patients and 105
      ethnically-matched healthy controls for class I A and B and II DR and DQ alleles.
      RESULTS: HLA-B5 (10% vs. 2%, p = 0.018) and DR2 (45% vs. 27%, p = 0.007) were
      positively associated and B15 (0% vs. 7%, p = 0.01) negatively associated with
      sarcoidosis compared to control subjects. Seventy-five patients were followed > 2
      years and 47 (63%) had chronic and 28 (37%) non-chronic disease. HLA-DR2 (55% vs.
      27%, p = 0.001) and DR11 (26% vs. 5%, p<0.0001) were significantly more frequent
      in chronic disease vs. controls, in contrast to HLA-DR3 (13% vs. 38%, p = 0.002),
      which had a significant negative association. HLA-B5 (11% vs. 2%, p = 0.029) and
      DR3 (64% vs. 38%, p = 0.005) were significantly more frequent in non-chronic
      disease. Of the 29 patients achieving spontaneous remission, 24 (83%) were HLA
      DR3 -positive and DR3-positivity was associated with significantly greater carbon
      monoxide diffusion at follow-up compared to DR3-negative patients (90% vs. 82%
      predicted, p = 0.027). CONCLUSIONS: This study supports the role of HLA-DR2 (15)
      as both a susceptibility and poor prognostic marker in sarcoidosis and DR2
      positive patients may particularly benefit from close follow-up and early
      treatment. In contrast, DR3 positive patients are at a much lesser risk of
      chronic disease. Studies for long-term treatment effects require stratification
      for HLA-DR2 and DR3 status.

PMID- 15554076
TI  - Production of IL-12, IL-18 and TNF-alpha by alveolar macrophages in
      hypersensitivity pneumonitis.
AB  - BACKGROUND AND AIM OF THE WORK: Hypersensitivity pneumonitis (HP) is
      characterized by a macrophage-lymphocyte alveolitis and granuloma formation. A
      wide range of cytokines have been implicated in the pathophysiology and
      development of granulomas in HP, but there is no information about the production
      of interleukin-12 (IL-12) and IL-18 by alveolar macrophages (AM) in human HP. We
      evaluated whether the production of IL-12, IL-18 and tumor necrosis factor-alpha
      (TNF-alpha) is locally increased in HP, and whether there is a correlation
      between these cytokines, as well as with the cellular profile of bronchoalveolar
      lavage (BAL) fluid in HP. METHODS: AM from 11 patients with HP and 10 control
      subjects were cultured for 24h in 10% RPMI medium alone, or with RPMI medium and
      lipopolysaccharide (LPS) (100 ng/ml). Cytokines in the culture supernatants were
      assayed by ELISA. RESULTS: The production of IL-18 and TNFalpha was increased in
      patients with HP in either absence or presence of LPS compared with controls.
      Although the spontaneous production of IL-12 was low, with LPS stimulation it was
      significantly elevated in HP. The concentration of the LPS-stimulated IL-12
      production positively correlated with the percentage of lymphocytes (r = 0.72, p
      = 0.011), and negatively correlated with the percentage of macrophages (r = 
      0.88, p < 0.001). CONCLUSIONS: These observations suggest that IL-12, IL-18 and
      TNFalpha may be involved in the pathogenesis of HP.

PMID- 15554077
TI  - T helper 1 inhibitor TAK-603 inhibits IFN-gamma and IL-12 production with no
      effect on IL-18: an observation in sarcoidosis patients.
AB  - BACKGROUND AND AIM: Sarcoidosis is immunologically characterized by highly
      enhanced Th1 responses in active stage. TAK-603 is a new quinoline derivative,
      which selectively suppresses Th1 cytokine production. Thus, the present study was
      designed to investigate whether TAK-603 ameliorates excess IFN-gamma production
      in active sarcoidosis. METHODS: We evaluated inhibitory effects of TAK-603 on IFN
      gamma, IL-12 and IL-18 production in stimulated bronchoalveolar lavage (BAL)
      fluid cells and peripheral blood mononuclear cells (PBMCs) of sarcoidosis
      patients and healthy subjects. RESULTS: TAK-603 inhibited IFN-gamma production in
      stimulated BAL fluid cells and PBMCs of sarcoidosis patients and healthy
      subjects. TAK-603 inhibited IL-12 production in stimulated BAL fluid cells of
      sarcoidosis patients and healthy subjects. TAK-603 tended to inhibit IL-12
      production in stimulated PBMCs of sarcoidosis patients and healthy subjects.
      However, TAK-603 did not affect IL-18 production in stimulated BAL fluid cells
      and PBMCs. TAK-603 did not affect TNF-alpha production in stimulated BAL fluid
      cells of sarcoidosis patients. TAK-603 inhibited IL-12 production in stimulated
      blood monocytes of healthy subjects, whereas IL-18 was increased by treatment
      with TAK-603. TAK-603 inhibited IFN-gamma production in PHA-stimulated blood T
      lymphocytes of healthy subjects with stimulation of IL-12 or a combination of IL
      12 and IL-18. TAK-603 did not increase IL-10 or TGF-beta1 production in LPS
      stimulated BAL fluid cells of sarcoidosis patients. CONCLUSIONS: TAK-603 inhibits
      IFN-gamma production in activated T lymphocytes and IL-12 production in activated
      monocytes/macrophages independently of increased production of IL-10 and TGF
      beta1. TAK-603 may ameliorate excess IFN-gamma production and be a therapeutic
      tool for refractory sarcoidosis.

PMID- 15554078
TI  - The incidence and clinical characteristics of bronchiolitis obliterans organizing
      pneumonia syndrome after radiation therapy for breast cancer.
AB  - STUDY OBJECTIVE: Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome
      after adjuvant radiation therapy for breast cancer has been recently recognized.
      However, the precise incidence of this syndrome remains to be determined. The aim
      of this study was to clarify the incidence and clinical characteristics of
      radiation-induced BOOP syndrome. METHODS: We conducted a retrospective analysis
      of 206 consecutive patients wit breast cancer undergoing tangential-field
      radiation therapy at our institution from 1992 to 2002. RESULTS: Among the
      patients, five (2.4%) developed BOOP syndrome. These five patients began with flu
      like symptoms 2-7 months after the completion of radiation therapy. Four of them
      had received tamoxifen, an estrogen receptor antagonist, and the other one
      underwent cytotoxic chemotherapy. Their chest radiographs revealed peripheral
      alveolar opacities with migration outside the irradiated fields. Increased
      lymphocyte counts and elevated CD4/CD8 ratios were observed in the
      bronchoalveolar lavage fluid. Transbronchial biopsy revealed organizing
      pneumonia. The serum levels of KL-6, a marker of interstitial pneumonia, did not
      increase in any patients. Treatment with corticosteroids resulted in a rapid
      improvement, but two patients relapsed after the cessation of corticosteroids.
      CONCLUSIONS: These results suggest that BOOP syndrome after tangential-field
      radiation therapy for breast cancer is not rare and more attention should be
      directed to this condition as a radiation-induced pulmonary toxicity.

PMID- 15554079
TI  - Clinical impact of inspiratory muscle impairment in sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: We evaluated the clinical consequences of
      inspiratory muscle impairment on exercise tolerance and quality of life in 34
      sarcoid patients compared with 19 controls. METHODS: We measured pulmonary
      function tests, inspiratory muscle strength by maximal inspiratory pressure
      (PImax) and inspiratory muscle endurance (IME) by an incremental threshold
      loading test. IME was defined by the maximal sustainable pressure for 2 minutes
      (Plim2) and Plim2/PImax. Cycloergometer incremental exercise testing was
      performed in all patients. Health-related quality of life (HRQOL) was assessed by
      the SF-36 questionnaire in comparison with scores of 116 French controls. Dyspnea
      was assessed by the Modified Dyspnea Index (MDI). RESULTS: All SF-36 subscales
      were lower in sarcoid patients (p < 0.05). PImax% pred was similar in both groups
      whereas IME was markedly lower in sarcoid patients (p < 0.0001). Plim2 correlated
      with MDI (r = 0.44; p = 0.01) and SF-36 scales Physical Functioning (PF) (r =
      0.42; p = 0.034) and Physical Role (PR) (r = 0.63; p = 0.0016). Plim2/PImax
      correlated with SF-36 subscales: PR (r = 0.62), vitality (VT) (r = 0.56) and
      social functioning (SF) (r = 0.39). Plim2 (r = 0.639; p = 0.0002) and Plim2/PImax
      (r = 0.36; p = 0.036) correlated with peak exercise tidal volume (V(T)max) but
      not with VO2max. CONCLUSIONS: Inspiratory muscle impairment was related to
      physical HRQOL scores but not to exercise tolerance, although it could impair
      exercising V(T) through an incipient inspiratory muscle fatigue.

PMID- 15554080
TI  - Sporadic Blau syndrome with a double CARD15 mutation. Report of a case with
      lifelong follow-up.
AB  - Blau syndrome (MIM 186580) is a rare granulomatous disorder inherited in an
      autosomal dominant manner characterized by the early appearance of granulomatous
      arthritis, skin rash and anterior uveitis. Missense mutations in CARD15, usually
      on codon 334, have been described in several families with Blau syndrome. The
      disorder has been described as familial; here we report the first evidence of a
      sporadic case of Blau syndrome in a 19 year-old man with two CARD15 mutations
      (R334Q and G908R). His healthy mother, father and brother did not carry the R334Q
      mutation, which was thus considered a neo-mutation, nor did they carry the other
      mutation, usually found in Crohn's disease. An extensive radiologic, histologic
      and laboratory evaluation and a life-long clinical follow-up is available for
      this patient who presented skin, joint, epididimal and eye involvement.

PMID- 15554081
TI  - Thymus tuberculosis poorly responding to anti-mycobacterial therapy in a young
      girl with primary infection.
AB  - Tuberculous infection of the thymus is a rare condition, previously described
      only in young adults. A case of a young girl with primary pulmonary tuberculosis,
      hilar and mediastinal lymph node enlargement and a partially necrotic mass in
      antero-superior mediastinum is described. Treatment with three anti-mycobacterial
      drugs was started, effective in markedly reducing all the intrathoracic
      abnormalities with the exception of the antero-superior mediastinal mass. Since
      the radiographic and ultrasonographic appearance of the thymus tuberculous
      infection may be indistinguishable from other serious conditions, including
      lymphoma and thymoma, a diagnostic procedure was performed. Evaluation of the
      resected specimen showed foci of caseation and multiple granulomas with extensive
      central necrosis within the thymic tissue.

PMID- 15554082
TI  - Mumps virus: a trigger for sarcoidosis?

PMID- 15554083
TI  - Spitzer's crusade.

PMID- 15554084
TI  - Money and morals at GE.

PMID- 15554085
TI  - The real secrets of entrepreneurs.

PMID- 15554086
TI  - 14 innovators. Staying creative, jazzing employees, keeping that startup vibe,
      and others tales from the front.

PMID- 15554087
TI  - Large problem. How big companies can innovate.

PMID- 15554088
TI  - Ways to beat the drug bust. Pharma stocks are down for good reasons, but that
      doesn't mean they're all bad bets.

PMID- 15554089
TI  - ECG of the month. Fatigue in a 34-year-old woman. Sinus bradycardia, right axis
      deviation, and right ventricular enlargement.
AB  - This obese, diabetic patient gives a history of a heart operation performed
      through a median sternotomy in the first year of her life. She is acyanotic and
      has a soft left parasternal systolic murmur that increases with inspiration. Her
      electrocardiogram (ECG) is shown below.

PMID- 15554090
TI  - Radiology case of the month. Gait disturbance. Lhermitte-Duclos disease
      (dysplastic gangliocytoma of the cerebellum).
AB  - An 18-year-old woman with a history of left temporal lobectomy for a deep
      epidermoid tumor.

PMID- 15554091
TI  - Pathology case of the month. 39-year-old woman with abdominal pain and weight
      loss. Takayasu's arteritis (TA).
AB  - A 39-year-old white woman presented with a history of aortoiliac occlusive
      disease diagnosed in 1992 attributed to oral contraceptive use. Shortly
      thereafter, aortoiliac replacement was performed. Mild hyperlipidemia was
      diagnosed in 2001. At the current clinic visit, she presented to her primary care
      physician with a 3-month history of postprandial midepigastric abdominal pain
      relieved by vomiting and a 30-pound weight loss. Her evaluation included an
      esophagogastroduodenoscopy, a colonoscopy, and an abdominal ultrasound, all of
      which were within normal limits. Because of her medical history, the patient
      underwent an arteriogram, which revealed brachiocephalic stenosis (Figure 1),
      occlusion of the left subclavian artery (Figures 2a and 2b), and narrowing of the
      superior and inferior mesenteric arteries (not shown). Since she had discontinued
      her oral contraceptives in 1992 and her hyperlipidemia was mild, the rheumatology
      service was consulted to evaluate this patient. On physical examination, she had
      decreased left brachial and radial pulses and a right carotid bruit. Laboratory
      evaluation revealed a normal complete blood count, comprehensive metabolic panel,
      erythrocyte sedimentation rate, and C - reactive protein. Subsequent testing
      included a prothrombin time, activated partial thromboplastin time, protein S,
      protein C, reptilase time, antithrombin III, anticardiolipin antibody,
      antiphospholipid antibody, lupus anticoagulant, homocysteine, RPR, and a lipid
      profile. All test results were within normal limits. Due to the severity of her
      abdominal pain, the patient underwent superior mesenteric artery (SMA) bypass
      surgery. Sections from the aorta resected in 1992 are shown in Figures 3 and 4.

PMID- 15554092
TI  - Clinical case of the month. 3-year-old boy presenting with a hand rash. Juvenile
      dermatomyositis.
AB  - Of the diseases within the spectrum of the juvenile idiopathic inflammatory
      myopathies, juvenile dermatomyositis (JDM) is the most common. As the name
      implies, JDM affects the muscles and skin most commonly, but can involve other
      organ systems as well. Dermatologic manifestations often precede other signs and
      symptoms by months or even years and frequently are the primary reason the
      patient seeks medical attention. In the case presented here, a 3-year-old boy
      initially developed a hand rash that brought him to his primary care physician.
      By the time muscle weakness had developed, the patient had already been evaluated
      for dermatomyositis and therapy had been initiated. An understanding of these
      early clinical findings will enable physicians to make a timely diagnosis and
      commence therapy promptly in order to prevent life-threatening sequelae of the
      disease.

PMID- 15554093
TI  - Hepatitis C genotype prevalence in south Louisiana: deviation from expected
      frequency and implications for treatment policy.
AB  - OBJECTIVES: To compare prevalence rates of hepatitis C genotypes in a southern
      Louisiana patient cohort to nationally accepted prevalence rates and to examine
      the possible impact on treatment cost effectiveness. METHODS: Systematic chart
      review of a community-based metropolitan gastroenterology practice. RESULTS:
      Hepatitis C genotype prevalence rates in the southeastern Louisiana cohort
      differed dramatically from nationally accepted figures, with only 12% prevalence
      of genotypes 2 and 3 infections combined. CONCLUSIONS: Regional variations in
      hepatitis C genotype prevalence in the United States should be fully explored, so
      that more accurate assessments of expected treatment outcomes and of costs can be
      promulgated.

PMID- 15554094
TI  - Head and neck manifestations in HIV infection.
AB  - Diseases of the head and neck often are the first sign of Human Immunodeficiency
      Virus (HIV) infection. As current treatment increases the survival time of HIV
      positive patients, the physician may encounter patients with a greater variety
      and number of diseases related to the primary HIV infection. Some entities are
      harbingers of HIV infection, such as Kaposi's sarcoma and parotid cystic
      enlargement. Other manifestations, such as Mycobacterium avium complex infection,
      may be used to determine the stage of HIV infection. The advent of highly active
      anti-retroviral therapy (HAART) has transformed the prevalence of HIV-associated
      head and neck disease. This article reviews the clinical presentations and
      treatments of common and uncommon head and neck manifestations in HIV infection.
      Accurate assessment of these conditions may allow the physician to identify HIV
      infection in previously undiagnosed patients, and, as a result, provide more
      timely treatment.

PMID- 15554095
TI  - Treatment patterns for stage III colon cancer and factors related to receipt of
      postoperative chemotherapy in Louisiana.
AB  - This study examined treatment patterns among Louisiana residents diagnosed with
      stage III colon cancer in 2001 and factors that may be related to the receipt of
      chemotherapy. The data were collected from hospital medical records, supplemented
      by information from physician offices. We examined the association of
      chemotherapy with race (whites and blacks), gender, health insurance status
      (private versus public/none), hospital type (hospitals with a cancer program
      approved by the Commission on Cancer of the American College of Surgeons [COC
      hospital] versus other hospitals [non-COC hospital]), comorbidity, area of
      residence (rural versus urban), and level of poverty of the area (high poverty
      versus low poverty) in univariate analyses and logistic multivariate regression
      models. Our study found that all patients received cancer-directed surgery, and
      66% received postoperative chemotherapy. The percentages of patients receiving
      chemotherapy were similar among race/gender groups. Patient age and hospital type
      were significantly associated with the receipt of chemotherapy even adjusting for
      other factors studied. The percentage of patients who received chemotherapy
      decreased with advancing age, and patients who were diagnosed at COC hospitals
      had a higher likelihood of receiving chemotherapy than their counterparts
      diagnosed at non-COC hospitals. Poverty and comorbidity were inversely associated
      (statistically significant) with the receipt of chemotherapy in univariate
      analysis. After adjusting for other factors, these associations were no longer
      significant. Although patients with private insurance were more likely to have
      chemotherapy than those with public insurance or no insurance, the difference was
      not significant. No difference was found in the receipt of chemotherapy between
      rural and urban patients.

PMID- 15554096
TI  - Acute endovascular management of a subclavian artery injury.
AB  - Traumatic injuries to the subclavian vessels are relatively uncommon and surgical
      repair may be technically challenging. With the increasing availability of
      endovascular techniques for nontraumatic arterial disease, an increase in the use
      of stenting for traumatic vascular injuries can be expected. This report
      describes the fifth successful endovascular repair with stenting of a
      pseudoaneurysm of the subclavian artery as a result of blunt trauma, and the
      first American report of such repair used in the acute or immediate management of
      blunt subclavian artery injury.

PMID- 15554097
TI  - High-dose cycles of dexamethasone in idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) in adults is usually
      treated with standard therapy using prednisone or methylprednisolone, adding
      intravenous immunoglobulin or Anti-D if necessary. This first episode of therapy
      frequently results in an early and satisfactory response, but remission is often
      temporary. As a series of relapses occur, or chronic low platelet counts persist,
      decisions on additional or alternative therapy are considered (i.e. splenectomy,
      chemotherapy). METHODS: High-dose dexamethasone in 4-day cycles (HD) has been
      used with some success reported in small numbers of patients with ITP. This
      retrospective analysis using HD in patients with ITP compared with standard
      therapy reports our experience at a large teaching hospital, comparing the timing
      and results of 26 episodes of treatment in 6 patients with no other underlying
      disease or complications. RESULTS: The six patients had nine Adequate Responses
      (AR's >100,000 platelets) in the 13 episodes using HD, and HD was successful in
      later episodes, 4th-7th. There were seven AR's in the 13 episodes using
      prednisone or methylprednisolone treatment. The time to remission and interval to
      relapse were similar after either intervention. CONCLUSIONS: This report of six
      patients with 26 episodes of treatment with standard therapy or HD provides
      additional data on HD as a useful alternative in patients with ITP, especially
      later in sequential relapses. The follow-up time in this group of patients is not
      sufficient to determine if modulation of the autoimmune process was achieved.
      Whether use of corticosteroids in repeated cycles, variation in doses, the
      timing, or the mechanism of action makes a difference in these autoimmune
      disorders remains to be established.

PMID- 15554099
TI  - Are insurers getting too big?

PMID- 15554098
TI  - Farewell address: "You're beautiful--catch you later.".

PMID- 15554100
TI  - Prescriptions.

PMID- 15554101
TI  - Referrals.

PMID- 15554102
TI  - Labs.

PMID- 15554104
TI  - Tips from an EMR pioneer.

PMID- 15554103
TI  - Controlled asthma.

PMID- 15554106
TI  - What primary care needs now.

PMID- 15554105
TI  - How hard are you working?

PMID- 15554107
TI  - Doc, can you write me a note?

PMID- 15554108
TI  - We settled, I lost.

PMID- 15554109
TI  - A physician's guide to antikickback rules.

PMID- 15554110
TI  - The feds take aim at kickback schemes.

PMID- 15554111
TI  - Haircut, manicure, and a little medicine.

PMID- 15554112
TI  - Revenue up, expenses down: our NP is paying off.

PMID- 15554113
TI  - Why Oregon's rationing plan is gasping for air.

PMID- 15554115
TI  - How to reactivate inactive patients.

PMID- 15554114
TI  - Bush vs Kerry: where they stand on healthcare.

PMID- 15554116
TI  - When to hire your own lawyer.

PMID- 15554117
TI  - Youth Risk Behavior Surveillance--United States, 2003 (Abridged).

PMID- 15554118
TI  - A contest to create media messages aimed at recruiting adolescents for stop
      smoking programs.
AB  - This project engaged adolescents in a contest to create advertising messages
      aimed at recruiting teens for stop smoking programs. Middle school students were
      invited to design a media message for television, radio, Web, or print (newspaper
      or billboard). Of 4,289 students in eight middle schools of Rochester, Minn., 265
      (6.2%) developed 172 stop smoking messages. The quality of their work confirmed
      that teens can design media messages to encourage their smoking adolescent peers
      to enroll in a program to stop smoking.

PMID- 15554119
TI  - A qualitative evaluation of the Students of Service (SOS) program for sexual
      abstinence in Louisiana.
AB  - Abstinence-only programs for preventing teen pregnancy are the only options in
      some states but are the programs of choice in others. Effectiveness data,
      however, are lacking. The SOS Adolescent Family Life Program (SOS), an abstinence
      only teen pregnancy prevention program, was implemented in south central
      Louisiana. Peer mentoring with an abstinence and life skills curriculum comprised
      the major components. SOS was implemented in the same grades in the same schools
      with new students each year for five years. During the final years of the
      program, qualitative evaluation was conducted with principals, teachers, peer
      mentors, and students. Use of peer mentors was reaffirmed as valuable; however,
      quality of peer mentoring was questioned and was a major issue for improvement.
      Other issues included: starting sexuality education in earlier grades, updating
      curricula and materials, offering more interactive classes, improving peer mentor
      training, and using teacher input to improve educational aspects of the program.
      Qualitative assessments provided valuable insights for future improvement in
      abstinence-only programs.

PMID- 15554120
TI  - Association of selected risk factors with variation in child and adolescent
      firearm mortality by state.
AB  - This study examined relationships between variation in child and adolescent
      firearm mortality by state and the following variables: childhood poverty rate,
      percent single parent families, percent population that is African American,
      percent population that is Hispanic, percent students carrying a gun, percent
      students carrying a weapon, percent students feeling unsafe, percent students
      feeling sad/hopeless, percent students academically at-risk, percent students
      involved infighting, percent students engaging in binge drinking behavior,
      violent crime rate for youths, individual gun laws in each state, prevalence of
      firearm ownership, and percent residing in urban area. Stepwise regression was
      calculated and one independent variable, prevalence of firearm ownership in the
      state, emerged as a significant predictor of child and adolescent firearm
      mortality. This variable predicted 47% of the variance from state to state in the
      child and adolescent firearm mortality. Schools need to address firearm safety
      and advocate for elimination of firearms accessible to youth.

PMID- 15554121
TI  - A mental health screening project in Istanbul, Turkey.

PMID- 15554122
TI  - Digital subtraction bowel cleansing for CT colonography using morphological and
      linear filtration methods.
AB  - We describe a method to perform postacquisition processing of computed tomography
      colonography (virtual colonoscopy) datasets that results in electronic removal of
      opacified, ingested bowel contents while reconstructing natural appearing
      boundaries of colon lumen and thereby permitting three-dimensional visual
      analyses of the resulting colon models.

PMID- 15554123
TI  - Colonic polyp segmentation in CT colonography-based on fuzzy clustering and
      deformable models.
AB  - An automatic method to segment colonic polyps in computed tomography (CT)
      colonography is presented in this paper. The method is based on a combination of
      knowledge-guided intensity adjustment, fuzzy c-mean clustering, and deformable
      models. The computer segmentations were compared with manual segmentations to
      validate the accuracy of our method. An average 76.3% volume overlap percentage
      among 105 polyp detections was reported in the validation, which was very good
      considering the small polyp size. Several experiments were performed to
      investigate the intraoperator and interoperator repeatability of manual colonic
      polyp segmentation. The investigation demonstrated that the computer-human
      repeatability was as good as the interoperator repeatability. The polyp
      segmentation was also applied in computer-aided detection (CAD) to reduce the
      number of false positive (FP) detections and provide volumetric features for
      polyp classification. Our segmentation method was able to eliminate 30% of FP
      detections. The volumetric features computed from the segmentation can further
      reduce FP detections by 50% at 80% sensitivity.

PMID- 15554124
TI  - Pulmonary airways: 3-D reconstruction from multislice CT and clinical
      investigation.
AB  - In the framework of computer-aided diagnosis, this paper proposes a novel
      functionality for the computerized tomography (CT)-based investigation of the
      pulmonary airways. It relies on an energy-based three-dimensional (3-D)
      reconstruction of the bronchial tree from multislice CT acquisitions, up to the
      sixth- to seventh-order subdivisions. Global and local analysis of the
      reconstructed airways is possible by means of specific visualization modalities,
      respectively, the CT bronchography and the virtual bronchoscopy. The originality
      of the 3-D reconstruction approach consists in combining axial and radial
      propagation potentials to control the growth of a subset of low-order airways
      extracted from the CT volume by means of a robust mathematical morphology
      operator-the selective marking and depth constrained (SMDC) connection cost. The
      proposed approach proved to be robust with respect to a large spectrum of airway
      pathologies, including even severe stenosis (bronchial lumen
      obstruction/collapse). Validated by expert radiologists, examples of airway 3-D
      reconstructions are presented and discussed for both normal and pathological
      cases. They highlight the interest in considering CT bronchography and virtual
      bronchoscopy as complementary tools for clinical diagnosis and follow-up of
      airway diseases.

PMID- 15554125
TI  - Three-dimensional path planning for virtual bronchoscopy.
AB  - Multidetector computed-tomography (MDCT) scanners provide large high-resolution
      three-dimensional (3-D) images of the chest. MDCT scanning, when used in tandem
      with bronchoscopy, provides a state-of-the-art approach for lung-cancer
      assessment. We have been building and validating a lung-cancer assessment system,
      which enables virtual-bronchoscopic 3-D MDCT image analysis and follow-on image
      guided bronchoscopy. A suitable path planning method is needed, however, for
      using this system. We describe a rapid, robust method for computing a set of 3-D
      airway-tree paths from MDCT images. The method first defines the skeleton of a
      given segmented 3-D chest image and then performs a multistage refinement of the
      skeleton to arrive at a final tree structure. The tree consists of a series of
      paths and branch structural data, suitable for quantitative airway analysis and
      smooth virtual navigation. A comparison of the method to a previously devised
      path-planning approach, using a set of human MDCT images, illustrates the
      efficacy of the method. Results are also presented for human lung-cancer
      assessment and the guidance of bronchoscopy.

PMID- 15554126
TI  - Depth-map-based scene analysis for active navigation in virtual angioscopy.
AB  - This paper presents a new approach dealing with virtual exploratory navigation
      inside vascular structures. It is based on the notion of active vision in which
      only visual perception drives the motion of the virtual angioscope. The proposed
      fly-through approach does not require a premodeling of the volume dataset or an
      interactive control of the virtual sensor during the fly-through. Active
      navigation combines the on-line computation of the scene view and its analysis,
      to automatically define the three-dimensional sensor path. The navigation
      environment and the camera-like model are first sketched. The basic stages of the
      active navigation framework are then described: the virtual image computation
      (based on ray casting), the scene analysis process (using depth map), the
      navigation strategy, and the virtual path estimation. Experimental results
      obtained from phantom model and patient computed tomography data are finally
      reported.

PMID- 15554127
TI  - Interactive virtual endoscopy in coronary arteries based on multimodality fusion.
AB  - A novel approach for platform-independent virtual endoscopy in human coronary
      arteries is presented in this paper. It incorporates previously developed and
      validated methodology for multimodality fusion of two X-ray angiographic images
      with pullback data from intravascular ultrasound (IVUS). These modalities pose
      inherently different challenges than those present in many tomographic modalities
      that provide parallel slices. The fusion process results in a three- or four
      dimensional (3-D/4-D) model of a coronary artery, specifically of its
      lumen/plaque and media/adventitia surfaces. The model is used for comprehensive
      quantitative hemodynamic, morphologic, and functional analyses. The resulting
      quantitative indexes are then used to supplement the model. Platform-independent
      visualization is achieved through the use of the ISO/IEC-standardized Virtual
      Reality Modeling Language (VRML). The visualization includes an endoscopic fly
      through animation that enables the user to interactively select vessel location
      and fly-through speed, as well as to display image pixel data or quantification
      results in 3-D. The presented VRML virtual-endoscopy system is used in research
      studies of coronary atherosclerosis development, quantitative assessment of
      coronary morphology and function, and vascular interventions.

PMID- 15554128
TI  - Shear modulus estimation using parallelized partial volumetric reconstruction.
AB  - Magnetic resonance elastography can be limited by the computationally intensive
      nonlinear inversion schemes that are sometimes employed to estimate shear modulus
      from externally induced internal tissue displacements. Consequently, we have
      developed a parallelized partial volume reconstruction approach to overcome this
      limitation. In this paper, we report results from experiments conducted on breast
      phantoms and human volunteers to validate the proposed technique. More
      specifically, we demonstrate that computational cost is linearly related to the
      number of subzones used during image recovery and that both subzone
      parallelization and partial volume domain reduction decrease execution time
      accordingly. Importantly, elastograms computed based on the parallelized partial
      volume technique are not degraded in terms of either image quality or accuracy
      relative to their full volume counterparts provided that the estimation domain is
      sufficiently large to negate the effects of boundary conditions. The clinical
      results presented in this paper are clearly preliminary; however, the
      parallelized partial volume reconstruction approach performs sufficiently well to
      warrant more in-depth clinical evaluation.

PMID- 15554129
TI  - Automatic quality control for wavelet-based compression of volumetric medical
      images using distortion-constrained adaptive vector quantization.
AB  - The enormous data of volumetric medical images (VMI) bring a transmission and
      storage problem that can be solved by using a compression technique. For the
      lossy compression of a very long VMI sequence, automatically maintaining the
      diagnosis features in reconstructed images is essential. The proposed wavelet
      based adaptive vector quantizer incorporates a distortion-constrained codebook
      replenishment (DCCR) mechanism to meet a user-defined quality demand in peak
      signal-to-noise ratio. Combining a codebook updating strategy and the well-known
      set partitioning in hierarchical trees (SPIHT) technique, the DCCR mechanism
      provides an excellent coding gain. Experimental results show that the proposed
      approach is superior to the pure SPIHT and the JPEG2000 algorithms in terms of
      coding performance. We also propose an iterative fast searching algorithm to find
      the desired signal quality along an energy-quality curve instead of a traditional
      rate-distortion curve. The algorithm performs the quality control quickly,
      smoothly, and reliably.

PMID- 15554130
TI  - Intensity-based image registration using robust correlation coefficients.
AB  - The ordinary sample correlation coefficient is a popular similarity measure for
      aligning images from the same or similar modalities. However, this measure can be
      sensitive to the presence of "outlier" objects that appear in one image but not
      the other, such as surgical instruments, the patient table, etc., which can lead
      to biased registrations. This paper describes an intensity-based image
      registration technique that uses a robust correlation coefficient as a similarity
      measure. Relative to the ordinary sample correlation coefficient, the proposed
      similarity measure reduces the influence of outliers. We also compared the
      performance of the proposed method with the mutual information-based method. The
      robust correlation-based method should be useful for image registration in
      radiotherapy (KeV to MeV X-ray images) and image-guided surgery applications. We
      have investigated the properties of the proposed method by theoretical analysis,
      computer simulations, a phantom experiment, and with functional magnetic
      resonance imaging data.

PMID- 15554131
TI  - Chebyshev series for designing RF pulses employing an optimal control approach.
AB  - Magnetic resonance imaging (MRI) provides bidimensional images with high
      definition and selectivity. Selective excitations are achieved applying a
      gradient and a radio frequency (RF) pulse simultaneously. They are modeled by the
      Bloch differential equation, which has no closed-form solution. Most methods for
      designing RF pulses are derived from approximation of this equation or are based
      on iterative optimization methods. The approximation methods are only valid for
      small tip angles and the optimization-based algorithms yield better results, but
      they are computationally intensive. To improve the solutions and to reduce
      processing time, a method for designing RF pulses using a pseudospectral approach
      is presented. The Bloch equation is expanded in Chebyshev series, which can be
      solved using a sparse linear algebraic system. The method permits three different
      formulations derived from the optimal control theory, minimum distance, minimum
      energy, or minimum time, which are solved as algebraic constrained minimization
      problems. The results were validated through simulated and real experiments of 90
      degrees and 180 degrees RF pulses. They show improvements compared to the
      corresponding solutions obtained using the Shinnar-Le Roux method. The minimum
      time formulation produces the best performance for 180 degrees pulses, reducing
      the excitation length in 4% and the RF pulse energy in 3%.

PMID- 15554132
TI  - Hobbits of the South Pacific. Why the discovery of a 3-ft.-tall dragon slayer is
      rewriting human history.

PMID- 15554133
TI  - Treats are a trap: but by following a few holiday rules, kids can have their cake
      and eat it too.

PMID- 15554134
TI  - Fighting for fitness: move over, curves. now there's a hot health club designed
      just for the boys.

PMID- 15554135
TI  - [Methodological bases for problem solution of monitoring and estimation of mental
      health services activity: national and international aspects].
AB  - General principles and questions, concerning the problem of monitoring and
      evaluation of psychiatric service's work from the points of systemic and
      mathematic modeling, are considered. An analysis of the structure and parameters
      values of national psychiatric service is presented. Suggested, are
      recommendations on using this information and improvement as well its collection,
      processing and presentation of the results in the national and international
      aspects. Taking Russia as an example, a selective correlation analysis of the
      regional rows of the values of the indices for psychiatric service's work was
      conducted to reveal their informational excessiveness. It is shown that the sets
      of the indices existed and being elaborated for solution of the monitoring
      problem and estimation of psychiatric service's work are excessively informative
      and can not be used without an additional analysis in corresponding mathematic
      modeling. In the view of the condition of the discussing questions, a use of
      hierarchical modeling apparatus seems to be the most natural and adequate for the
      solution of the problems posited.

PMID- 15554136
TI  - [Gunshot injuries of peripheral nervous system: the questions of classification
      and diagnostics].
AB  - Two hundreds and sixty-seven patients with gunshot injuries of 394 nerves and
      plexus underwent clinical and electromyographic investigation and H-reflex
      evaluation as well. Based on the results of the data obtained, 3 types of nerves
      trunk injuries: neuroapraxia, axonothmesis and neurothmesis, were identified. The
      reduction of biopotential amplitude and synergic muscular activity, decrease of
      impulse conduction velocities (ICVeff--up to 30%), M-response amplitude (up to
      50% and more) and motor units functioning were characteristic of neuroapraxia of
      nerve trunks. Axonothmesis of nerve trunks featured by the reduction of the
      amplitude and frequency of muscular biopotentials, decrease of its synergic
      activity, marked reduction of ICVeff (30--60%), rough fall of M-response
      amplitude and motor units functioning. In neurothmesis of nerve trunks,
      "bioelectrical silence" and disappearance of synergic muscular activity as well
      as an absence of M-response of denervated muscles were observed. An evaluation of
      monosynaptic reflex has a substantial significance for the determination of the
      level of low extremities injuries.

PMID- 15554137
TI  - [Affective phases in dynamics of personality disorders (on a model of borderline
      personality disorder)].
AB  - Affective phases developing in personality disorder (index-sample--98 patients)
      were compared to those in cyclothymia (85 patients--control group). A preference
      of phase dynamics in the group of abnormalities relating to ICD-10 item
      "Borderline personality disorder" was confirmed. In line with a concept
      considering personality disorders as clinical syndromes, patients of the index
      group have personality disorders with the signs of psychopathological diathesis
      determined by vulnerability to affective disorders. Affective phases are
      interpreted not only as an expression of a specific type of personality disorders
      dynamics but as an emergence of affective pathology, which is alternative to
      endogenous one both by modus of constitutional predisposition and clinical
      parameters (egosyntonic moderating of the phase, domination of negative
      affectivity in its structure, amphitymic duality of pathologically altered
      affect).

PMID- 15554138
TI  - [Clinical symptoms, pathopsychological peculiarities and mechanisms of biographic
      amnesia].
AB  - Clinical and pathopsychological analysis of 16 men, aged 15-53 years, was carried
      out. In premorbid stage, hysterical, hystero-epileptoid, schizoid, emotional
      unstable features were found in 12 patients and personality accentuation--in 4
      patients. There were the absence of marked cognitive disturbances and safety
      operational functions of intellect, i.e. memory. In all patients, the projective
      pathopsychological tests allowed determining subjectively significant
      disturbances of interpersonal communication that, in combination with selective
      character of amnesia and intact character of formal intellect, suggested
      functional mechanisms underlying the analyzing state.

PMID- 15554139
TI  - [Therapy of epilepsy: current strategy and tactics].
AB  - The article addresses the current strategy and tactics of epilepsy treatment,
      which suggest instead of the thesis "to start pharmacotherapy as soon as
      possible" the antithesis--"do not treat, when it is not necessary". The thesis
      "to start treatment always from monotherapy" is substituted for some forms of the
      disease by the antithesis "polytherapy--from the beginning: from successive
      monotherapy to alternative poly(duo)therapy". Psychological peculiarities of an
      interaction between a patient and a physician, age, gender and body mass and
      their impact on the treatment results as well as the problems of teratogenic
      influence of antiepileptic drugs (AED) on the fetus and risk factors for
      polycystic ovarii are analyzed. The author suggests a hypothesis on potential
      negative influence of any AED on epileptic seizures and, in light of pseudo- and
      true drug resistant epilepsy, analyzes the own observations of 1957-2000 period,
      which indicate a significant role of novel AED (carbamasepine, depakin,
      lamotrigine) in reducing of true drug resistance.

PMID- 15554140
TI  - [Topamax in monotherapy of epilepsy].
AB  - Thirty-three patients, aged 3-29 years, with the following epileptic types:
      symptomatic forehead (15), symptomatic temporal (6), symptomatic occipital (2),
      juvenile myoclonic, in combination with eyelid myoclonus syndrome with absences,
      (5), epilepsy with isolated generalized seizures (3) and rolandic epilepsy (2),
      were treated with topamax. A medication dose was 50-200 mg per day in children
      younger 12 years and 100-550 mg per day in those older 12 years and in adults.
      The results obtained suggest the high efficacy and well tolerability of topamax
      in monotherapy of epilepsy. Therapeutic effect was achieved in 28 out of 33
      patients (84.8%), i.e. seizures stopping--in 18 patients (54.5%). Monotherapy was
      mostly effective in symptomatic forehead epilepsy: seizures stopped in 53.3%
      patients and a frequency of seizures reduced in 33.3%. Side-effects were detected
      only in 18% cases, they were mostly transient and resulted in treatment
      withdrawal in 6% patients only.

PMID- 15554141
TI  - [A use of betaserc in ataxic syndromes].
AB  - Thirty-five patients with vestibular (25) and cerebellar (10) ataxy were
      medicated by betacerc during 21 days. A status of balance function was estimated,
      using stabilometric complex MBN "Biomechanika", before and after the treatment
      course. After the end of the treatment, symptoms of static ataxy and vertigo were
      reduced. An analysis of stabilogramm has confirmed a tendency to normalization of
      static balance parameters as a result of betacerc treatment of vestibular and
      cerebella types of ataxy, with significant decrease of general length of the way,
      area of support and velocity of gravity center displacement.

PMID- 15554142
TI  - [A role of depression in chronic dorsalgia: approaches to therapeutic
      correction].
AB  - An impact of depression on general clinical picture was studied in 20 patients
      with chronic dorsalgia, who were treated with coaxil. Along with complaints to
      prolonged back pains, patients featured by high depression and anxiety, sleep
      disturbances, autonomic dysfunction and marked decrease of quality of life.
      Psychometric tests revealed a presence of depressive symptoms in 90% of the
      cases. All patients were treated with coaxil in dosage 12.5 mg 3 times daily
      during 6 weeks. The treatment allowed a reduction of depression and anxiety
      symptoms, along with muscle dysfunction and pain syndrome. Positive dynamics of
      autonomic dysfunction, sleep disturbances and quality of life was observed
      already at the initial treatment stage. The results of the study confirm the fact
      that depression develops in patients with chronic dorsalgia, influencing
      negatively on the course of pain syndrome. Coaxil was shown to have high efficacy
      and safety in the treatment of depression caused by chronic back pain and
      positively influence on the main syndrome.

PMID- 15554143
TI  - [A use of Magne-B6 in the treatment of anxiety-depressive states in patients with
      epilepsy].
AB  - Magne-B6 was used, together with anticonvulsive therapy, in the treatment of 25
      patients with different forms of epilepsy. In all cases, psychiatric status of
      patients featured by depression, anxiety and some psychotic sighs. The drug was
      prescribed in the mean therapeutic dose during 28 days. Along with
      psychopathologic examination, a psychometric method, using self-rating scales for
      Zung anxiety and depression scale, SCL-90 and Global clinical impression (CGI)
      scale, was administered. Magne-B6 exerted a positive non-specific influence on
      patient's mental state, especially with regard to affective disorders. The
      positive effect of the drug emerged on 14th day of the treatment and achieved a
      statistically significant level to 28th day. The medication was more effective in
      asthenic and subdepressive syndromes, in encephalopathic syndrome the efficacy
      was lower. The drug was well tolerated and did not cause any side effects.

PMID- 15554144
TI  - [A therapy of eating disorders in children and adolescents].
AB  - Eighty patients with anorexia nervosa, 66 girls and 14 boys, aged 6-16 years,
      illness duration 6-44 months, were examined and treated. Sixty-seven patients
      were follow-up studied during 3-10 years. In 30 cases, anorexia nervosa emerged
      in the frame of pathological course of the age crisis in children and
      adolescences with accentuated personality features; in 50 cases--as syndrome in
      the frame of schizotypal personality disorder. The treatment was realized stage
      by-stage and included "nonspecific" therapy directed to ceasing of weight deficit
      and stopping the increase of cahexia; "specific" psychotropic therapy conducted
      with taking into account a nosologic affiliation of syndrome and combined with
      psychotherapy and family therapy. An implication of the complex therapy allowed
      to increase a patient's body mass and to reduce motivational, autonomic,
      emotionally-affective disorders. A combination of "nonspecific" and "specific"
      treatment stages with psychotherapy made it possible to form and reinforce a
      stable right style of eating behavior in patients with syndrome of anorexia
      nervosa that was supported by positive dynamics and favorable follow-up results.

PMID- 15554145
TI  - [Efficacy and safety of antiepileptic therapy in children (a comparative analysis
      of valproates and barbiturates)].
AB  - The study aimed at a comparative analysis of safety and efficacy of valproic acid
      (valproate) and barbiturates in the treatment of epilepsy in children. Two
      hundred and forty children were treated with valproate, 94% being assigned to
      depakine and depakine chrono, and 210 children received barbiturates. Therapeutic
      effect (a decrease of seizures frequency by 2 and more times or remission) was
      detected in 82 of 127 (65 +/- 8.53%) patients for valproate monotherapy and only
      in 26 of 89 (30 +/- 9.45%) for barbiturates monotherapy. An efficacy of
      antiepileptic therapy in children was significantly higher (p<0.05) for
      valproates as compared to barbiturates. A drug withdrawal due to poor
      tolerability was recorded in 6 of 127 (5 +/- 3.7%) patients treated with
      valproate in monotherapy and in 14 of 210 (7 +/- 3.45%)--in polytherapy; in 53 of
      89 (59 +/- 10.2%) patients treated with barbiturates in monotherapy and in 78 of
      121 (65 +/- 8.53%) patients treated with barbiturates in polytherapy. Therefore,
      adverse effects occurred more often in barbiturates than in valproate treatment
      both for mono- and polytherapy (p<0.05). The results of the study confirmed the
      high efficacy and safety of valproates, specifically depakine chrono, in the
      treatment of epilepsy in children. depakine chrono in-take is associated with
      lower frequency of adverse effects; side-effects are mostly of dose-dependent
      character and do not result in the drug withdrawal. The authors do not recommend
      using barbiturates in the first-line treatment in children, because of the lower
      efficacy, high frequency of medical complications that might result in the drug
      withdrawal and reducing of the efficacy of other antiepileptic medications.

PMID- 15554146
TI  - [Clinical and genetic analysis of juvenile parkinsonism in Russia].
AB  - Clinical and genetic analysis of juvenile parkinsonism was performed in 26 sibs
      from 20 families. Heterogeneity of the disorder was observed. Mutations in the
      parkin gene (locus PARK2, chromosome 6q25.2-27), with the prevalence of deletions
      over point mutations, have been identified in 41%. The comparative clinical
      analyses of patients examined confirmed the phenotypical polymorphism of
      "parkinopathy". We also showed the absence of asymmetric manifestation--an
      important and underestimated so far sign of the disease. The results of the study
      may be considered as a valuable clue to the clinical diagnosis of parkin-related
      juvenile parkinsonism in Russian population and implemented for mutation
      screening and medico-genetic counseling of affected families.

PMID- 15554147
TI  - [Motor system: structure, functions, terminology].

PMID- 15554148
TI  - [Neurotransmitter organization of brain and spinal cord motor systems in normal
      and pathological state].

PMID- 15554149
TI  - [Pharmacogenetic challenges in the treatment of mental diseases].

PMID- 15554150
TI  - Protein engineering and applications of Candida rugosa lipase isoforms.
AB  - Commercial preparations of Candida rugosa lipase (CRL) are mixtures of lipase
      isoforms used for the hydrolysis and synthesis of various esters. The presence of
      variable isoforms and the amount of lipolytic protein in the crude lipase
      preparations lead to a lack of reproducibility of biocatalytic reactions.
      Purification of crude CRL improve their substrate specificity,
      enantioselectivity, stability, and specific activities. The expression of the
      isoforms is governed by culture or fermentation conditions. Unfortunately, the
      nonsporogenic yeast C. rugosa does not utilize the universal codon CTG for
      leucine; therefore, most of the CTG codons were converted to universal serine
      triplets by site-directed mutagenesis to gain expression of functional lipase in
      heterologous hosts. Recombinant expressions by multiple-site mutagenesis or
      complete synthesis of the lipase gene are other possible ways of obtaining pure
      and different CRL isoforms, in addition to culture engineering. Protein
      engineering of purified CRL isoforms allows the tailoring of enzyme function.
      This involves computer modeling based on available 3-D structures of lipase
      isoforms. Lid swapping and DNA shuffling techniques can be used to improve the
      enantioselectivity, thermostability, and substrate specificity of CRL isoforms
      and increase their biotechnological applications. Lid swapping can result in
      chimera proteins with new functions. The sequence of the lid can affect the
      activity and specificity of recombinant CRL isoforms. Candida rugosa lipase is
      toxicologically safe for food applications. Protein engineering through lid
      swapping and rationally designed site-directed mutagenesis will continue to lead
      to the production of CRL isoforms with improved catalytic power, thermostability,
      enantioselectivity, and substrate specificity, while providing evidence for the
      mechanisms of actions of the various isoforms.

PMID- 15554151
TI  - Dietary intakes and food sources of n-6 and n-3 PUFA in French adult men and
      women.
AB  - The intake of individual n-6 and n-3 PUFA has been estimated in 4,884 adult
      subjects (2,099 men and 2,785 women), volunteers from the French SU.VI.MAX
      intervention trial. The food intakes of each subject were recorded in at least
      ten 24-h record questionnaires completed over a period of 2.5 yr, allowing the
      estimation of the daily intake of energy; total fat; and linoleic, alpha
      linolenic, arachidonic, eicosapentaenoic (EPA), n-3 docosapentaenoic (DPA), and
      docosahexaenoic (DHA) acids. The mean total fat intake corresponded to 94.1 g/d
      (36.3% of total energy intake) in men and 73.4 g/d (38.1% of energy) in women.
      The intake of linoleic acid was 10.6 g/d in men and 8.1 g/d in women,
      representing 4.2% of energy intake; that of alpha-linolenic acid was 0.94 g/d in
      men and 0.74 g/d in women, representing 0.37% of energy intake, with a mean
      linoleic/alpha-linolenic acid ratio of 11.3. The mean intakes of long-chain PUFA
      were: arachidonic acid, 204 mg/d in men and 152 mg/d in women; EPA, 150 mg/d in
      men and 118 mg/d in women; DPA, 75 mg/d in men and 56 mg/d in women; DHA, 273
      mg/d in men and 226 mg/d in women; long-chain n-3 PUFA, 497 mg/d in men and 400
      mg/d in women. Ninety-five percent of the sample consumed less than 0.5% of
      energy as alpha-linolenic acid, which is well below the current French
      recommendation for adults (0.8% of energy). In contrast, the mean intakes of long
      chain n-6 and n-3 PUFA appear fairly high and fit the current French
      recommendations (total long-chain PUFA: 500 mg/d in men and 400 mg/d in women;
      DHA: 120 mg/d in men and 100 mg/d in women). The intakes of alpha-linolenic acid,
      and to a lesser extent of linoleic acid, were highly correlated with that of
      lipids. Whereas the main source of linoleic acid was vegetable oils, all food
      types contributed to alpha-linolenic acid intake, the main ones being animal
      products (meat, poultry, and dairy products). The main source of EPA and DHA (and
      of total long-chain n-3 PUFA) was fish and seafood, but the major source of DPA
      was meat, poultry, and eggs. Fish and seafood consumption showed very large
      interindividual variations, the low consumers being at risk of insufficient n-3
      PUFA intake.

PMID- 15554153
TI  - Incorporation of n-3 fatty acids into plasma and liver lipids of rats: importance
      of background dietary fat.
AB  - The health benefits of long-chain n-3 PUFA (20:5n-3 and 22:6n-3) depend on the
      extent of incorporation of these FA into plasma and tissue lipids. This study
      aimed to investigate the effect of the background dietary fat (saturated,
      monounsaturated, or n-6 polyunsaturated) on the quantitative incorporation of
      dietary 18:3n-3 and its elongated and desaturated products into the plasma and
      the liver lipids of rats. Female weanling Wistar rats (n = 54) were randomly
      assigned to six diet groups (n = 9). The fat added to the semipurified diets was
      tallow (SFA), tallow plus linseed oil (SFA-LNA), sunola oil (MUFA), sunola oil
      plus linseed oil (MUFA-LNA), sunflower oil (PUFA), or sunflower oil plus linseed
      oil (PUFA-LNA). At the completion of the 4-wk feeding period, quantitative FA
      analysis of the liver and plasma was undertaken by GC. The inclusion of linseed
      oil in the rat diets increased the level of 18:3n-3, 20:5n-3, and, to a smaller
      degree, 22:6n-3 in plasma and liver lipids regardless of the background dietary
      fat. The extent of incorporation of 18:3n-3, 20:5n-3, and 22:5n-3 followed the
      order SFA-LNA > MUFA-LNA > PUFA-LNA. Levels of 22:6n-3 were increased to a
      similar extent regardless of the type of major fat in the rat diets. This
      indicates that the background diet affects the incorporation in liver and plasma
      FA pools of the n-3 PUFA with the exception of 22:6n-3 and therefore the
      background diet has the potential to influence the already established health
      benefits of long-chain n-3 fatty acids.

PMID- 15554152
TI  - Effects of specific conjugated linoleic acid isomers on growth characteristics in
      obese Zucker rats.
AB  - Growing female obese Zucker (fa/fa) rats were treated (via intragastric gavage)
      for 21 d with either a (i) vehicle [corn oil; 0.9 g/kg body weight (BW)], (ii)
      CLA mixture [50:50; trans-10, cis-12 and cis-9, trans-11 CLA], (iii) cis-9,trans
      11 CLA, or (iv) trans- 10, cis-12 CLA (CLA treatments at 1.5 g CLA/kg BW).
      Compared with controls, average daily gain (g/d) was reduced 24 and 44% by the
      CLA mixture and trans-10, cis-12 CLA, respectively. There was no treatment effect
      on average whole-body (minus heart and liver) composition (dry matter basis): fat
      (70.2%), protein (21.0%), and ash (4.3%). Compared with animals treated with cis
      9,trans-11 CLA, obese Zucker rats treated with trans-10, cis-12 and the CLA
      mixture had 7.8% more carcass water. Treatment had no effect on heart or liver
      weights or on heart or liver weights as a percentage of body weight, but compared
      with the other treatments trans-10, cis-12 CLA increased liver lipid content by
      33%. Hepatic lipid ratios of 16:1/16:0 and 18:1/18:0 (a proxy for delta9
      desaturase capability) were not affected by treatment (0.1 and 0.6,
      respectively). Similar to previous reports, CLA increased hepatic lipid content
      and altered both liver and carcass FA composition (i.e., reduced arachidonic acid
      content), but the ability of CLA to manipulate body composition in obese Zucker
      rats remains questionable.

PMID- 15554155
TI  - A developmental study on the appearance of tocopherols and tocotrienols in
      developing palm mesocarp (Elaeis guineensis).
AB  - The concentration of vitamin E isomers, namely, alpha-tocopherol (alpha-T), alpha
      tocotrienol, gamma-tocotrienol, and delta-tocotrienol in palm mesocarp at 4, 8,
      12, 16, and 20 wk after anthesis (WAA) were quantified using HPLC coupled with
      fluorescence detection. alpha-T was detected throughout the palm fruits'
      maturation process, whereas unsaturated tocotrienols were found only in ripe palm
      fruits. These developmental results indicate that tocotrienols are synthesized
      between 16 and 20 WAA.

PMID- 15554154
TI  - Phospholipase D and phosphatidate phosphohydrolase activities in rat cerebellum
      during aging.
AB  - Aging is a process that affects different organs, of which the brain is
      particularly susceptible. PA and DAG are central intermediates in the
      phosphoglyceride as well as in the neutral lipid biosynthetic pathway, and they
      have also been implicated in signal transduction. Phospholipase D (PLD) and
      phosphatidate phosphohydrolase (PAP) are the enzymes that generate PA and DAG.
      The latter can be transformed into MAG by diacylglycerol lipase (DGL). In the
      present study, we examine how aging modulates the PLD, PAP, and DGL isoforms in
      cerebellar subcellular fractions from 4- (adult), 28-, and 33-mon-old (aged)
      rats. PI-4,5-bisphosphonate (PIP2)-dependent PLD, PAP1, and DGL1 were distributed
      in different percentages in all cerebellum subcellular fractions. On the other
      hand, PAP2 and DGL2 activities were observed in all subcellular fractions except
      in the cytosolic fraction. Aging modified the enzyme distribution pattern. In
      addition, aging decreased nuclear (45%), mitochondrial-synaptosomal (55%), and
      cytosolic (71%) PAP1 activity and increased (28%) microsomal PAP1 activity. DGL1
      activity was decreased in nuclear (85%) and mitochondrial-synaptosomal (63%)
      fractions by aging. On the other hand, PIP2-dependent PLD activities were
      increased in the mitochondrial-synaptosomal fraction. PAP2 and DGL2 were
      increased in the microsomal fraction by 87 and 114%, respectively, and they were
      decreased in the nuclear fraction. The changes observed in cerebellum PAP1 and
      DGL1 activities from aged rats with respect to adult rats could be related to
      modifications in lipid metabolism. Differential PA metabolization during aging
      through PIP2-dependent PLD/PAP2/DGL2 activities could be related to alterations
      in the neural signal transduction mechanisms.

PMID- 15554157
TI  - Geranium sanguineum (Geraniaceae) seed oil: a new source of petroselinic and
      vernolic acid.
AB  - The occurrence of petroselinic acid (18:1delta6cis) in seed oils was believed to
      be limited to the Umbelliferae or Apiaceae, and a few other members of the
      Umbelliflorae. A major occurrence of petroselinic acid outside the Umbelliflorae
      must therefore be regarded as highly unusual and surprising. The seed oil of
      Geranium sanguineum, a member of the family Geraniaceae, has now been found to
      contain petroselinic and vernolic acids as major FA in its seed oil TAG. These
      unusual FA have not been reported previously as constituents of Geraniaceae seed
      oils. The structure and composition of the seed oil FA from G. sanguineum were
      determined by combined use of chromatographic (TLC, capillary GLC) and
      spectroscopic (IR, GC-MS) techniques. The double-bond position in petroselinic
      acid was located unambiguously by the characteristic mass fragmentation of its
      dimethyldisulfide (DMDS) adduct. The epoxy FA was identified as vernolic acid by
      co-chromatography and by the mass fragments formed during GC-MS of the products
      of the epoxy ring-opening reaction with BF3 in methanol.

PMID- 15554156
TI  - Isolation and structures of two divinyl ether fatty acids from Clematis vitalba.
AB  - [1-14C]Linolenic acid was incubated with a homogenate of leaves of Clematis
      vitalba, a plant belonging to the Ranunculaceae family. Analysis of the reaction
      product by reversed-phase high-performance liquid radiochromatography
      demonstrated the presence of the following labeled oxylipins: 12-oxo-10, 15(Z)
      phytodienoic acid, 9(S)-hydroxy-10(E), 12(Z), 15(Z)-octadecatrienoic acid,
      omega5(Z)-etherolenic acid, and 9-[1'(E), 3'(Z),6'(Z)-nonatrienyloxy]-8(Z)
      nonenoic acid [8(Z)-colnelenic acid]. The last compound was a new divinyl ether
      FA, and an analogous compound, i.e., 9-[1'(E),3'(Z)-nonadienyloxy]-8(Z)-nonenoic
      acid [8(Z)-colneleic acid], was obtained following incubation of linoleic acid
      with the Clematis homogenate. Structures of the two divinyl ethers were assigned
      by spectral and chromatographic comparison with authentic compounds prepared
      synthetically using previously described methodology. Separate incubation of the
      9- and 13-hydroperoxides of linolenic acid demonstrated that the first
      hydroperoxide served as the precursor of 8(Z)-colnelenic acid and indicated the
      presence in C. vitalba of a new divinyl ether synthase acting on 9-lipoxygenase
      generated hydroperoxides. A close structural relationship between this enzyme and
      the well-studied divinyl ether synthase in the potato and tomato seems likely.

PMID- 15554158
TI  - Photochemical production of conjugated linoleic acid from soybean oil.
AB  - Conjugated linoleic acid (CLA), an anticarcinogenic compound with numerous other
      health benefits, is present mainly in dairy and beef lipids. The main CLA isomer
      present in dairy and beef lipids is cis 9, trans 11 CLA at a 0.5% concentration.
      The typical minimum human dietary intake of CLA is 10 times less than the 3 g/d
      suggested requirement that has been extrapolated from animal and cell-line
      studies. The objectives of this study were to produce CLA isomers from soybean
      oil by photoisomerization of soybean oil linoleic acid and to study the oxidation
      status of the oil. Refined, bleached, and deodorized soybean oil with added
      iodine concentrations of 0, 0.1, 0.25, and 0.5% was exposed to a 100-W mercury
      lamp for 0 to 120 h. An SP-2560 fused-silica capillary GC column with FID was
      used to analyze the esterified CLA isomers in the photoisomerized oil. The CLA
      content of the individual isomers was optimized by response surface methodology.
      Attenuated total reflectance (ATR)-FTIR spectra in the 3400 to 3600 cm(-1) range
      and 1H NMR spectra in the 8 to 12 ppm range of the photoisomerized soybean oil
      were obtained to follow hydroperoxide formation. The largest amount of cis 9,
      trans 11 CLA isomer in soybean oil was 0.6%, obtained with 0.25% iodine and 84 h
      of photoisomerization. Lipid hydroperoxide peaks in the ATR-FTIR spectra and
      aldehyde peaks in the 1H NMR spectra were not observed in the photoisomerized
      soybean oil, and the spectra were similar to that of fresh soybean oil. This
      study shows that CLA isomers can be produced simply and inexpensively from
      soybean oil by photoisomerization.

PMID- 15554159
TI  - Reaction of mono-epoxidized conjugated linoleic acid ester with boron trifluoride
      etherate complex.
AB  - The reaction of methyl 11,12-E-epoxy-9Z-octadecenoate (1) with boron trifluoride
      etherate furnished a mixture of methyl 12-oxo-10E-octadecenoate (3a) and methyl
      11-oxo-9E-octadecenoate (3b) in 66% yield. Methyl 9,10-Z-epoxy-11E-octadecenoate
      (2) with boron trifluoride etherate furnished a mixture of methyl 9-oxo-10E
      octadecenoate (4a, 45%) and methyl 10-oxo-11E-octadecenoate (4b, 19%). A
      plausible mechanism is proposed for these reactions, which involves the attack on
      the epoxy ring system by BF3, followed by deprotonation, oxo formation, and
      double bond migration to give a mixture of two positional alpha,beta-unsaturated
      C18 enone ester derivatives (3a/3b, 4a/4b). The structures of these C18 enone
      ester derivatives (3a/3b, 4a/4b) were identified by a combination of NMR
      spectroscopic and mass spectrometric analyses.

PMID- 15554160
TI  - Successful utilization of lyophilized lipoprotein(a) as a biological reagent.
AB  - Lipoprotein(a) [Lp(a)] represents a class of lipoprotein particles having as a
      protein moiety apoB-100 linked by a single disulfide bond to apolipoprotein(a)
      [apo(a)], a multikringle structure with a high degree of homology with
      plasminogen. A recognized feature of Lp(a) is its instability on storage caused
      by attendant protein and lipid modifications that affect the structural,
      functional, and immunological properties of this lipoprotein. Here we present
      data showing that, under appropriate conditions of cryopreservation, Lp(a)
      retains the properties of the freshly isolated product, and we provide examples
      supporting the stability of this cryopreserved product as a primary standard in
      immunoassay settings and in cell culture systems.

PMID- 15554161
TI  - A short, concise route to diphosphatidylglycerol (cardiolipin) and its variants.
AB  - A new approach is described for the synthesis of the cardiolipin family of
      phospholipids that uses phosphonium salt methodology. The method involves the
      reaction of 2-O-protected glycerol with a trialkyl phosphite derived from 1,2
      diacylsn-glycerol in the presence of pyridinium bromide perbromide and
      triethylamine to afford the phosphoric triesters. The synthesis involves three
      steps and allows the preparation of a wide range of cardiolipins with different
      substitution patterns and chain lengths, including unsaturated derivatives. The
      use of inexpensive protecting groups and the ease of purification facilitate this
      synthetic route and allow its scale-up in a higher overall yield (72%) than the
      literature methods.

PMID- 15554162
TI  - Re: Effect of dietary protein and CLA interaction on lipid metabolism in rats.

PMID- 15554163
TI  - The new federal overtime rules.

PMID- 15554164
TI  - Avoiding communication problems (and lawsuits).

PMID- 15554165
TI  - What can I charge patients for copying their dental records?

PMID- 15554166
TI  - Top 10 factors that determine the value and desirability of a practice.

PMID- 15554167
TI  - New services add value to your membership.

PMID- 15554168
TI  - Why does insurance reduce the amount billed on the claim?

PMID- 15554169
TI  - I was addicted to everything.

PMID- 15554170
TI  - Treating the Alzheimer's patient. A guide for dental professionals.

PMID- 15554172
TI  - Make plans now for your January CE courses.

PMID- 15554171
TI  - "Give Kids a Smile" 2005 planning tips and timelines.

PMID- 15554173
TI  - Players and fans--both are crucial to success.

PMID- 15554174
TI  - It's time to stand up for ourselves.

PMID- 15554175
TI  - Business basics. Physicians often learn practice management by trial and error.

PMID- 15554176
TI  - William Scurlock, MD. Interview by Samantha Brady.

PMID- 15554177
TI  - Constipation not always benign.

PMID- 15554178
TI  - Sickle cell syndromes: misdiagnosis can affect treatment.

PMID- 15554179
TI  - The cost of living in purgatory's shadow.
AB  - A 40-year-old alcoholic man developed Wernicke-Korsakoff syndrome. His
      examination showed ophthalmoplegia, ataxia and memory difficulties. His cranial
      magnetic resonance imaging scan showed increased signal in the paraventricular
      regions of the thalamus on T-2 weighted, diffusion and axial fluid-attenuated
      inversion recovery sequences consistent with the syndrome. The ophthalmoplegia
      resolved with thiamine administration; however, his memory did not improve.

PMID- 15554180
TI  - Occupational disparities in smoke-free workplace policies in Arkansas.
AB  - This report summarizes trends in Arkansas to protect workers from the documented
      harm caused by secondhand smoke. We also examined whether employees comply with
      smoke-free policies. FINDINGS: While considerable progress has been made to
      protect workers from secondhand smoke, Arkansas workers report significantly
      lower rates of smoke-free policies than workers nationally and ranked 46th among
      the states in this important area of occupational health in 2001-02. Blue-collar
      and service workers in the state lag significantly behind their white-collar
      counterparts and men report lower rates of smoke-free policies than women. Once
      implemented, however, compliance with a smoke-free policy is nearly universal
      among working Arkansans.

PMID- 15554181
TI  - [The role of weak specific and nonspecific interactions in recognition and
      conversation by enzymes of long DNA].
AB  - According to a currently accepted model, enzymes engage in high-rate sliding
      along DNA when searching for specific recognition sequences or structural
      elements (modified nucleotides, breaks, single-stranded DNA fragments, etc.).
      Such sliding requires these enzymes to possess sufficiently high affinity for DNA
      of any sequence. Thus, significant differences in the enzymes' affinity for
      specific and nonspecific DNA sequences cannot be expected, and formation of a
      complex between an enzyme and its target DNA unlikely contributes significantly
      in the enzyme specificity. To elucidate the factors providing the specificity we
      have analyzed many DNA replication, DNA repair, topoisomerization, integration,
      and recombination enzymes using a number of physicochemical methods, including a
      method of stepwise increase in ligand complexity developed in our laboratory. It
      was shown that high affinity of all studied enzymes for long DNA is provided by
      formation of many weak contacts of the enzymes with all nucleotide units covered
      by protein globules. Contacts of positively charged amino acid residues with
      internucleotide phosphate groups contribute most to such interactions; the
      contribution of each contact is very small and the full contact interface usually
      resembles interactions between oppositely charged biopolymer surfaces. In some
      cases significant contribution to the affinity is made through hydrophobic and/or
      van der Waals interactions of the enzymes with nucleobases. Overall, depending on
      the enzyme, such nonspecific interactions provide 5-8 orders of the enzyme
      affinity for DNA. Specific interactions of enzymes with long DNA, in contrast to
      contacts of enzymes with small ligands, are usually weak and comparable in
      efficiency with weak nonspecific contacts. The sum of specific interactions most
      often provides approximately one and rarely two orders of the affinity. According
      to structural data, DNA binding to any of the investigated enzymes is followed by
      a stage of DNA conformation adjustment including partial or complete DNA melting,
      deformation of its backbone, stretching, compression, bending or kinking,
      eversion of nucleotides from the DNA helix, etc. The full set of such changes is
      characteristic for each individual enzyme. The fact that all enzyme-dependent
      changes in DNA are effected through weak specific rather than strong interactions
      is very important. Enzyme-specific changes in DNA conformation are required for
      effective adjustment of reacting orbitals with accuracy about 10-15 degrees,
      which is possible only for specific DNA. A transition from nonspecific to
      specific DNA leads to an increase in the reaction rate (kcat) by 4-8 orders of
      magnitude. Thus, the stages of DNA conformation adjustment and catalysis proper
      provide the high specificity of enzyme action.

PMID- 15554182
TI  - [Specificiety of DNA-protein interactions within transcription complexes of
      Escherichia coli].
AB  - Current requirement for description of each new promoter assumes identification
      of all DNA-protein and protein-protein contacts important for transcription
      complex formation. Experimental approaches allow estimating which one of seven
      alternative sigma-subunits is employed for RNA synthesis and verifying
      transcription dependence on known regulatory proteins. Promoter sequence by
      itself also contains this information. That is why, the type of promoter as well
      as potential regulatory proteins with high probability may be proposed, if the
      transcription start point has been determined. Transcription activity of the
      promoter is usually less predictive. It depends on the specific contacts formed
      by sigma-subunits with correspondent conservative elements and on many other non
      specific factors that are hardly taken into account. Interaction with RNA
      polymerase alpha-subunits seems does not require any particular functional group
      of nucleotides thus exemplifying non-sequence-specific binding within binary
      polymerase-promoter complexes. The role of this interaction in the transcription
      complex formation is the main subject of this survey that summarizes our own
      experimental results and the data of other authors. Attempts have been made to
      compare nucleotide sequences of the promoters recognized by different sigma
      factors within putative contact regions with alpha-subunits and to discuss
      regulatory propensity of free alpha-subunits.

PMID- 15554183
TI  - [RNA synthesis by T7 RNA polymerase supported primer extension].
AB  - Transcription of RNA molecules from synthetic DNA templates with T7 RNA
      polymerase is a common procedure for the preparation of long RNA molecules.
      However, enzymatic synthesis does not allow for site-specific incorporation of
      modified nucleotides. RNA synthesis by chemical methods on the other side can
      satisfy this purpose, but it is limited to RNA fragments of about 80 nucleotides
      at maximum. We aimed to combine both chemical and enzymatic procedures to
      synthesise RNA molecules by RNA primed transcription with T7 RNA polymerase. To
      this end we have chemically synthesised a fluorescein labelled RNA primer and
      studied elongation of this primer by T7 RNA polymerase on a single-stranded DNA
      template. We show that the enzyme is capable of extending the primer to the full
      length product. The 34-mer RNA that has been synthesised by RNA primed
      transcription served as substrate for a twin ribozyme and was successfully
      cleaved in the expected manner.

PMID- 15554184
TI  - [Nucleotide-dependent degradation of nucleic acids by DNA and RNA polymerases].
AB  - In this review we summarize the current knowledge about recently discovered
      reactions of nucleotide-dependent nucleic acid degradation catalyzed by DNA and
      RNA polymerases. These reactions consist in the excision of the 3'-nucleotide of
      nascent DNA or RNA chain in the presence of non-complementary r/dNTPs. In the
      case of DNA polymerases the dinucleoside-5',5"-tetraphosphate as a product of the
      reaction is formed. In contrast, in the case of RNA polymerases non-complementary
      r/dNTPs stimulate 3'-->5' exonuclease degradation of RNA transcript. The possible
      role of these reactions in fidelity of DNA and RNA synthesis, in resistance of
      HIV reverse transcriptase towards nucleoside inhibitors is discussed.

PMID- 15554185
TI  - [Antimutagenic role of autonomous 3'-->5'-exonucleases].
AB  - Our own and literary data about antimutagenic role of autonomous 3'-->5'
      exonucleases (AE) are analyzed. AE are not bound covalently to DNA polymerases
      but often involved in replicative complexes. Intracellular overproduction of AE
      in bacteria is accompanied with the sharp suppression of mutagenesis, whereas the
      inactivation of AE in bacteria and higher fungi results in the increase of
      mutation rates by 2-3 orders of magnitude. The addition of AE in biologically
      meaningful concentrations to DNA polymerases elevates substantially the accuracy
      of their work in vitro. In these cases, the reverse mutation rates were measured
      in the DNA from phage (X174 amber 3, whereas the direct mutation rates--in the
      DNA from phage M13mp2, both being used as primer-templates for DNA synthesis and
      then transfected into spheroplasts of Escherichia coli. The accuracy of action of
      nuclease-free DNA polymerases alpha and beta are shown to raise in the presence
      of AE by 2-3 orders, the accuracy of moderately processive DNA polymerase I--by 2
      orders, the accuracy of highly processive DNA polymerase delta--by 5-10 times,
      though the latter 2 polymerases display and their own 3'-->5'-exonucleolytic
      activity. AE, involved in the multienzyme DNA polymerase complexes, augment the
      accuracy of complexes action by 5-10 times. The model of "external" corrective
      role of AE in DNA biosynthesis is proposed. Study of 30 objects from all 3
      kingdoms of live beings (from archae- and eubacteria to mammalia including human)
      has shown that AE account, as minimum, from 30 to 90% of the total cellular 3'-
      >5'-exonucleolytic activity. So AE increase essentially the intracellular ratio
      of values of 3'-->5'-exonuclease to DNA polymerase activities in the very various
      representatives from a phylogenetic tree that results always in the augmentation
      of the accuracy of DNA biosynthesis.

PMID- 15554186
TI  - [Poly(ADP-ribose) polymerase-1 as a regulator of protein-nucleic acid
      interactions in the processes responding to genotoxic action].
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1), nuclear protein of higher eukaryotes,
      specifically detects strand breaks in DNA. When bound to DNA strand breaks, PARP
      1 is activated and catalyzes synthesis of poly(ADP-ribose) covalently attached to
      the row of nuclear proteins, with the main acceptor being PARP-1 itself. This
      protein participates in a majority of DNA dependent processes: repair,
      recombination; replication: cell death: apoptosis and necrosis. Poly(ADP
      ribosyl)ation of proteins is considered as mechanism, which signals about DNA
      damage and modulate protein functioning in response to genotoxic impact. The main
      emphasis is made on the roles of PARP-1 and poly(ADP-ribosyl)ation in base
      excision repair (BER), the process, which provides repair of DNA breaks. The main
      proposed functions of PARP-1 in this process are: factor initiating assemblage of
      protein complex of BER; temporary protection of DNA ends; modulation of chromatin
      structure via poly(ADP-ribosyl)ation of histones; signaling function in detection
      of the levels of DNA damage in cell.

PMID- 15554187
TI  - [Interactions of HIV-1 DNA heterocyclic bases with viral DNA].
AB  - Human immunodeficiency virus type 1 integrase is one of three viral enzymes, and
      it realizes a key process of the viral replication cycle, i.e. viral DNA
      integration into infected cell genome. Integrase recognizes nucleotide sequences
      located at the ends of the viral DNA U3 and U5 LTRs and catalyzes 3'-processing
      and strand transfer reactions. To study the interactions between integrase and
      viral DNA at present work, we used modified integrase substrates mimicking the
      terminal U5 LTR sequence and containing non-nucleoside insertions in one or/and
      both strands. It is shown that the substrate modifications have no influence on
      the integrase binding rate, while the heterocyclic bases removal in the 5th and
      6th substrate positions and in the 3rd position of the substrate processed strand
      distinctly inhibits the integrase catalytic activity. This fact demonstrates
      these bases significance for the active enzyme/substrate complex formation. On
      the contrary, modification of the 3rd position within substrate non-processed
      strand stimulates 3'-processing. Since heterocyclic base elimination results in
      disruption of the DNA complementary and staking interactions, this result shows
      that DNA double helix destabilization close to the cleaved bond promotes the 3'
      processing.

PMID- 15554188
TI  - [New non-hydrolyzable substrate analogs for 8-oxoguanine-DNA glycosylases].
AB  - 8-Oxoguanine-DNA glycosylases play a key role in the repair of oxidatively
      damaged DNA. The Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) and
      human 8-oxoguanine-DNA glycosylase (hOGG1) are DNA base excision repair enzymes
      that catalyze the removal of 7,8-dihydro-8-oxoguanine (oxoG) residue, and cleave
      DNA strand. Specific contacts between DNA phosphate groups and amino acids from
      active centers of these enzymes play a significant role in DNA-protein
      interactions. In order to design new non-hydrolyzable substrate analogs of Fpg
      and hOGG1 for structural studies modified DNA duplexes containing pyrophosphate
      or OEt-substituted pyrophosphate internucleotide (SPI) groups near the damage
      were tested. We showed that enzymes recognize and specifically bind to DNA
      duplexes obtained. The mechanism of incision of oxoG by the Fpg and hOGG1 was
      determined. We revealed that both enzymes were not able to excise the oxoG
      residue from DNA containing modified phosphates immediately 3' to the oxoG. In
      contrast, Fpg and hOGG1 effectively incise DNA duplex carrying analogous
      phosphate modifications 5' to the oxoG. Non-cleavable oxoG-containing DNA
      duplexes bearing pyrophosphate or substituted pyrophosphate groups immediately 3'
      to the oxoG are specific inhibitors for both 8-oxoguanine-DNA glycosylases and
      can be used for structural studies of complexes comprising a oxoG-containing DNA
      bound to catalytically active wild-type enzymes as well as their pro- and
      eucaryotic homologs.

PMID- 15554189
TI  - [Molecular enzymology of phage T4 Dam DNA-methyltransferase].
AB  - The review reflects results of studies on the molecular mechanism of phage T4 Dam
      DNA-methyltransferase action. The enzyme (T4Dam) catalyzes methyl group transfer
      from S-adenosyl-l-methionine (AdoMet) to N6-adenine position in the palindromic
      recognition sequence GATC (EC 2.1.1.72). The enzyme subunit structure, substrate
      binding and kinetic parameters for a wide range of native and modified
      oligonucleotide duplexes, as well as steady-state reaction kinetic scheme,
      included T4Dam isomerization to catalytically active form, are considered. The
      found mechanisms of DNA induced T4Dam dimerization, target base flipping, enzyme
      reorientation in an asymmetrically modified recognition sequence, effector action
      of reaction substrates and processive methylation of DNA substrates, containing
      more than one specific site, are discussed. The results obtained with T4Dam may
      be useful for understanding mechanisms of action of other homologous enzymes,
      most of all for specimens of numerous family of Dam DNA-methyltransferases.

PMID- 15554190
TI  - [Type IIE and IIF restriction endonucleases interacting with two recognition
      sites in DNA].
AB  - Recently, it was revealed that restriction endonucleases widely used in genetic
      engineering and molecular biology are diverse not only in DNA sequence
      specificities but also in mechanisms of their interaction with DNA. In the review
      type IIE and IIF restriction endonucleases which require the simultaneous
      interaction with two copies of their recognition sequence for effective
      hydrolysis of DNA are considered. Crystal structures of these enzymes and their
      complexes with DNA as well as stepwise interaction with DNA, mechanisms of
      catalysis and enzyme-mediated DNA looping are discussed. A novel type of DNA
      protein recognition was found for type IIE endonucleases when two copies of the
      same DNA sequence specifically interact with two different amino acid sequences
      and two structural motifs located in one polypeptide chain.

PMID- 15554191
TI  - [Antirestriction activity of the IncI1 transmissive plasmid R64 ArdA protein].
AB  - The transmissive plasmid IncI1 R64 contains the ardA gene encoding the ArdA
      antirestriction protein. The R64 ardA gene locating in the leading region of
      plasmid R64 has been cloned and their sequence has been determined.
      Antirestriction proteins belonging to the Ard family are specific inhibitors of
      type I restriction-modification enzymes. The IncI1 ColIb-P9 and R64 are closely
      related plasmids, and the latter specifies an ArdA homologue that is predicted to
      be 97.6% (162 residues from 166) identical at the amino acid sequence level with
      the ColIb = P9 equivalent. However, the R64 ArdA selectively inhibits the
      restriction activity of EcoKi enzyme leaving significant levels of modification
      activity under conditions in which restriction was almost completely prevented.
      The ColIb-P9 ArdA inhibits restriction endonuclease and methyltransferase
      activities simultaneously. It is hypothesized that the ArdA protein forms two
      complexes with the type I restriction-modification enzyme (R2M2S): (1) with a
      specific region in the S subunit involved in contact with the sK site in DNA; and
      (2) with nonspecific region in the R subunit involved in DNA translocation and
      degradation by restriction endonuclease. The association of the ColIb-P9 ArdA
      with the specific region inhibits restriction endonuclease and methyltransferase
      activities simultaneously, whereas the association of the R64 ArdA with a
      nonspecific region inhibits only restriction endonuclease activity of the R2M2S
      enzyme.

PMID- 15554192
TI  - [Using of 4-thiouridine and 4-thiothymidine for pyrimidine nucleoside
      phosphorylase studing].
AB  - 4-Thiouridine and 4-thiothymidine were developed as efficient substrates for
      spectrophotometric determination of uridine phosphorylase and thymidine
      phosphorylase activity. 4-Thiouridine has maximum absorbance at 330 nm (pH 7.5).
      The change in extinction coefficient for 4-thiouridine/4-thiouracil, deltaepsilon
      is 3000 M(-1) x cm(-1). It appeared that 4-thiouridine is a good substrate for
      uridine phosphorylase with Michaelis-Menten constant 130 microM and kcat 49 s(
      1). In the case of 4-thiothymidine/4-thiothymine deltaepsilon is even larger:
      5000 M(-1) x cm(-1) at 336 nm.

PMID- 15554193
TI  - [Trans-translation: main participants and role in the cell life].
AB  - Trans-translation, the unique process of the synthesis of the single polipeptide
      chain from both mRNA and the coding part of tmRNA, is necessary for the cell
      viability in the changeable environment. The new data concerning the main
      participants and physiological role of trans-translation and the conditions in
      which it occurs are summarized. The possible tmRNA function in the translation
      quality control is also discussed.

PMID- 15554194
TI  - [Identification of RNA-recognizing modules on the surface of ribosomal proteins].
AB  - Properties of specific interaction between ribosomal proteins and ribosomal RNAs
      were analyzed and a method for determination of "recognizing modules" on the
      protein surface was proposed. The method is based on the search of protein atoms
      making conserved H-bonds with RNA and forming an invariant spatial structure in
      homologous rRNA-protein complexes and in the isolated protein. A potential of the
      method is demonstrated on the determination of the recognizing modules on the
      surfaces of ribosomal proteins S8, S15 and L5.

PMID- 15554195
TI  - [Escherichia coli ribosomes as the model to test new photoactivated tRNA
      analogues, containing 6-thioguanosine].
AB  - Photoreactive derivatives of tRNAs, containing 6-thioguanosine or diazirine
      derivative of 5-methyleneaminouridine were compared as probes to modify
      Escherichia coli ribosomes. The derivatives of tRNA were synthesized by T7
      transcription Proportion of the modified nucleotide analogues was optimised to
      obtain good yield, analogue incorporation and binding to the ribosome. Complexes
      of the tRNA analogues with the ribosomal P-site were irradiated with mild UV
      light. Cross-links were analysed by oligonucleotide-directed hydrolysis of rRNA
      by RNase H and reverse transcription. 6-thioguanosine was proved to be a
      perspective reagent for cross-linking studies of complex ribonucleoproteides.

PMID- 15554196
TI  - [Investigation of helical plant virus ribonucleoprotein structures with the help
      of tritium planigraphy and theoretical modeling].
AB  - The results of the studies of helical plant virus structures by tritium
      planigraphy (TP) method are discussed. TP method is based on bombardment of
      macromolecular objects with a stream of tritium atoms, followed by analysis of
      tritium label distribution along the macromolecule. By combining the TP data with
      the results of theoretical predictions of the protein structure, it turned out to
      be possible to propose a model of the coat protein structure in the virions of
      potato virus X (the type member of potexvirus group) and potato virus A (one of
      the members of potyvirus group). With the help of TP it also managed to find
      subtle differences in the coat protein structure between wildtype tobacco mosaic
      virus (strain U1) and its mutant with two amino acid substitutions in the coat
      protein and alter host specificity.

PMID- 15554197
TI  - [Current problems in epilepsy treatment].

PMID- 15554198
TI  - [Epilepsy: classification and basal mechanisms].

PMID- 15554199
TI  - [Diagnostic imaging in epilepsy].

PMID- 15554200
TI  - [Pitfalls in the diagnosis of epilepsy].

PMID- 15554201
TI  - [Status epilepticus].

PMID- 15554202
TI  - [Psychosocial consequences of epilepsy].

PMID- 15554203
TI  - [Fertility, contraception and pregnancy in patients with epilepsy].

PMID- 15554204
TI  - [Antiepileptic treatment of adults with epilepsy].

PMID- 15554205
TI  - [Antiepileptic treatment of children: 12 good recommendations to physicians
      treating the disease].

PMID- 15554206
TI  - [Surgical treatment for children with epilepsy].

PMID- 15554207
TI  - [Epilepsy surgery seen from a Danish point of view].

PMID- 15554208
TI  - [Mesial temporal lobe epilepsy--is surgery an effective treatment?].

PMID- 15554209
TI  - [Morbidity and mortality in epilepsy].

PMID- 15554210
TI  - [Apnea as a primary manifestation of epilepsy].

PMID- 15554211
TI  - [Glucosamine/cholesterol a possible interaction].

PMID- 15554212
TI  - [Pyogenic granulomas].

PMID- 15554213
TI  - [All surgical interventions are educational].

PMID- 15554214
TI  - [Educational crisis within gastrointestinal surgery].

PMID- 15554215
TI  - Hot air coating technique as a novel method to produce microparticles.
AB  - In this work a new technology to produce microparticles, as well as the equipment
      suitable for its application, is described. This technique, called hot air
      coating (HAC), was developed to overcome the drawbacks of the conventional spray
      congealing technique and consists of a special venturimeter, deliberately
      designed to prevent any hindrance along the axial path through which the powder
      is conveyed. In HAC technology, the raw material is a solid, generally small
      granules, which is aspirated through the "Venturi effect" and accelerated in a
      flux of hot air to soften and then to melt the excipient, especially on the
      particle surface. The microparticles then solidify during falling in air at room
      temperature. Model formulations, containing acetaminophen or theophylline as
      drugs and glycerilmonostearate, stearic acid, or carnauba wax as coating waxes,
      were tested. The choice of the optimal operating parameters was found to be a
      function of the formulation and of the particle size of the starting material. A
      pressure of 3 atm and a temperature of 20-60 degrees C above the melting point of
      the excipient were found generally to be the optimal parameters for the coating
      process. The morphology, the in vitro dissolution profile, and the possible
      drug/excipient interactions of formulations containing different percentages
      (30%, 50%, and 70% w/w) of acetaminophen were evaluated. The results show that
      the morphology and dissolution profiles of the microparticles were quite
      different from those of the starting material; in particular the best coating was
      achieved by microparticles lower than 500 microm. Therefore, the HAC process
      could be a viable alternative to the conventional spray-congealing technique to
      produce microparticles with a high drug content.

PMID- 15554216
TI  - A rapid micro quantification method of paracetamol in suppositories using
      differential scanning calorimetry.
AB  - This study adopts Differential Scanning Calorimetry (DSC) to analyze the thermal
      properties of samples (2.5-4.0 mg) from the tip, middle, and base sections of
      individual paracetamol suppositories, which were sampled carefully using a
      stainless steel scalpel. The contents of paracetamol present in the samples
      obtained from these sections were determined from the enthalpies of fusion of
      paracetamol and expressed as % w/w paracetamol to allow comparison of the amount
      of paracetamol found in each section. The tip, middle, and base sections
      contained 10.1+/-0.2%, 10.1+/-0.2%, and 10.3+/-0.2% w/w paracetamol, and are
      statistically similar (One-way anova; p>0.05). This indicates that the
      preparation technique adopted produces high quality suppositories in terms of
      content uniformity. The contents of paracetamol in the 120-mg paracetamol
      suppositories determined by DSC and UV spectrophotometry were statistically
      equivalent (Students's t-test; p>0.05), 120.8+/-2.6 mg and 120.8+/-1.5 mg,
      respectively, making DSC a clear alternative method for the measurement of
      content of drug in suppositories. The main advantages of the method are that
      samples of only 2.5-4.0 mg are required and the procedure does not require an
      extraction process, which allows for the analysis to be completed rapidly. In
      addition, it is highly sensitive and reproducible, with the lower detection limit
      at 4.0% w/w paracetamol, which is about 2.5 times lower than the content of
      paracetamol (10% w/w) present in our 120-mg paracetamol suppositories and
      commercial paracetamol suppositories, which contained about 125 mg paracetamol.
      Therefore, this method is particularly suited for determination of content
      uniformity in individual suppositories in quality control (QC) and in process
      quality control (PQC).

PMID- 15554217
TI  - Development of the bioadhesive tetracaine gels for enhanced local anesthetic
      effects.
AB  - To develop the new local anesthetic formulations with a suitable bioadhesive
      property, hydroxypropyl methylcellulose (HPMC)-based gel was formulated. As the
      drug concentration in the gels, and the temperature of surrounding solutions
      increased, the drug release increased. The activation energy of tetracaine
      permeation was 4.47 kcal/mol. The effects of permeation enhancers on the
      permeation rate of drug through skin were studied using various enhancers, such
      as the glycols, the nonionic surfactants, and the bile salts. Among the enhancers
      used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects on drug
      permeation through skin. The analgesic activity was examined using a tail-flick
      analgesimeter. In the AUEC (area under the efficacy curve) of the rat-tail flick
      test, tetracaine gel containing polyoxyethylene 2-oleyl ether showed about 3.2
      fold increase in analgesic activity compared with the control. The results of
      this study support that the tetracaine gels with efficient anesthetic effects
      could be developed using HPMC and poloxamer with combination of enhancer and
      vasoconstrictor.

PMID- 15554218
TI  - Comparison studies on the percolation thresholds of binary mixture tablets
      containing excipients of plastic/brittle and plastic/plastic deformation
      properties.
AB  - Percolation theory has been used with great interest in understanding the design
      and characterization of dosage forms. In this study, work has been carried out to
      investigate the behavior of binary mixture tablets containing excipients of
      similar and different deformation properties. The binary mixture tablets were
      prepared by direct compression using lactose, polyvinyl chloride (PVC), Eudragit
      RS 100, and microcrystalline cellulose (MCC). The application of percolation
      theory on the relationships between compactibility, Pmax, or compression
      susceptibility (compressibility), gamma, and mixture compositions reveals the
      presence of percolation thresholds even for mixtures of similar deformation
      properties. The results showed that all mixture compositions exhibited at least
      one discreet change in the slope, which was referred to as the percolation
      threshold. The PVC/Eudragit RS100 mixture compositions showed significant
      percolation threshold at 80% (w/w) PVC loading. Two percolation thresholds were
      observed from a series of binary mixtures containing similar plastic deformation
      materials (PVC/MCC). The percolation thresholds were determined at 20% (w/w) and
      80% (w/w) PVC loading. These are areas where one of the components percolates
      throughout the system and the properties of the tablets are expected to
      experience a sudden change. Experimental results, however, showed that total
      disruption of the tablet physical properties at the specified percolation
      thresholds can be observed for PVC/lactose mixtures at 20-30% (w/w) loading while
      only minor changes in the tablets' strength for PVC/MCC or PVC/Eudragit RS 100
      mixtures were observed.

PMID- 15554219
TI  - The macromolecular polymers for the preparation of hydrodynamically balanced
      systems--methods of evaluation.
AB  - Evaluation of macromolecular polymers used as excipients for the preparation of
      hydrodynamically balanced systems (HBS) was carried out. Hard gelatine capsules
      were filled with polymeric substances belonging to various chemical groups
      (chitosan, sodium alginate, hydroxypropylmethycellulose--HPMC). The following
      properties of the HBS were investigated: density, hydration, erosion and floating
      force. The solvent penetration process into the HBS was visualized using magnetic
      resonance imaging (MRI) technique. Densities of the HBS in hydrochloric acid (0.1
      M) ranged from 0.37 g/cm3 to 0.71 g/cm3. Each polymer demonstrated different
      hydration/erosion abilities and floating properties. The maximum floating force
      (F(float max)) for capsules size 0, ranged from 26.7 mN (sodium alginate) to 64.7
      mN (chitosan). HBS formulations also varied in time to reach maximum floating
      force (T(float max)). HPMC and sodium alginate formulation reached F(float max)
      within half an hour after immersion, while in the case of chitosan formulations
      (deacetylation degree (d.d.) 66% and d.d. 93%), the time was 184 minutes and 218
      minutes respectively. The floating properties of the dosage forms were reliant on
      type of the polymer and the medium-fasted state simulated gastric fluid (FaSSGF)
      or fed state simulated gastric fluid (FeSSGF). The size of the HBS influenced the
      floating force value. The mechanisms of erosion and swelling of the polymeric
      matrices play a dominant role in flotation of the dosage forms.

PMID- 15554220
TI  - Studies on acyclovir-dextran conjugate: synthesis and pharmacokinetics.
AB  - Acyclovir is an antivirus drug which has a good in vitro activity against
      hepatitis B virus. But because of the low solubility and low distribution in
      liver, the clinical application of acyclovir in hepatitis B was limited. To
      increase the solubility and the distribution in liver, acyclovir-dextran
      conjugate was synthesized by formation of Schiff's base. The solubility of
      obtained conjugate was 12 times greater than free acyclovir. Acyclovir will be
      slowly released from the obtained conjugate in pH 7.4 phosphate buffer solution
      (PBS) at 37 degrees C with a rate constant of 0.0035 hr(-1). Pharmacokinetic
      studies of acyclovir and acyclovir-dextran conjugate were conducted in mice by
      i.v. administration. Acyclovir concentrations in plasma, liver and kidney were
      determined by HPLC method. Relatively higher distribution of acyclovir in liver
      was observed when i.v. acyclovir-dextran conjugate as compared with i.v. free
      acyclovir. The results of pharmacokinetic studies indicated that acyclovir
      dextran conjugate will be a good candidate to treat hepatitis B.

PMID- 15554221
TI  - Solution stability of factor Xa inhibitors as a function of pH.
AB  - The stability of two factor Xa inhibitors (MLN1021 and CT54004) as a function of
      pH was investigated in order to better characterize the compounds and to locate
      the optimum pH for a stable formulation that might be used in a first-in-person
      (FIP) clinical study. The compounds prepared in buffer solutions over a pH range
      of 1-10 were stored at 60 degrees C, and assayed for pH and purity at different
      time points. The pH-rate profiles indicated that both compound was quite stable
      in the middle pH range, and least stable at pH<3 and >8. The optimum pH for
      stability of the compounds was around 6, which is consistent with the theoretical
      predictions by a mathematical model. The mechanism of the reaction is not a
      specific-acid/base-catalyzed reaction. Based on the experience of this study, an
      ideal experimental design is proposed, which will be useful for future study on
      similar drug candidate.

PMID- 15554222
TI  - Physicochemical characterization and in vitro release of salicylic acid from O/W
      emulsions prepared with Montanov 68: effect of formulation parameters.
AB  - Montanovs are surfactants consisting of a combination of alkylpolyglucosides and
      long chain saturated alcohols. They are used to formulated oil in water (O/W)
      emulsions where they generate liquid crystals. Emulsions containing 5% Montanov
      68 with 40% Lanol 1688 were prepared and salicylic acid (SA) was incorporated at
      different stages of the O/W emulsion preparation. This study highlights the
      effects of formulation parameters on the microscopic characteristics, particle
      size and rheologic properties of Montanov 68 O/W emulsions. Diffusion studies
      with these emulsions showed the influence of SA incorporation at different steps
      on the release kinetics. Montanov enabled the release of SA to be controlled when
      it was solubilized in the internal phase. The presence of a physical barrier
      formed by the Montanov at the interface between the oil and water appeared to
      modulate the SA passage to the external phase.

PMID- 15554223
TI  - Mucoadhesive delivery systems. I. Evaluation of mucoadhesive polymers for buccal
      tablet formulation.
AB  - Different types of mucoadhesive polymers, intended for buccal tablet formulation,
      were investigated for their comparative mucoadhesive force, swelling behavior,
      residence time and surface pH. The selected polymers were carbopols (CP934, and
      CP940), polycarbophil (PC), sodium carboxymethyl cellulose (SCMC) and pectin
      representing the anionic type, while chitosan (Ch) as cationic polymer and
      hydroxypropylmethyl cellulose (HPMC) as a non-ionic polymer. Results revealed
      that polyacrylic acid derivatives (PAA) showed the highest bioadhesion force,
      prolonged residence time and high surface acidity. SCMC and chitosan ensured
      promising bioadhesive characteristics, whilst HPMC and pectin exhibited weaker
      bioadhesion. Different polymer combinations as well as formulations were
      evaluated to improve the mucoadhesive performance of the tablets. Bioadhesive
      tablet formulations containing either 5% CP934, 65% HPMC and 30% spray-dried
      lactose or 2% PC, 68% HPMC and 30% mannitol showed optimum mucoadhesion and
      suitable residence time. SCMC, when formulated individually, exhibited promising
      bioadhesion, acceptable swelling, convenient residence time and surface pH. In
      vivo trials of these formulations proved non-irritative and prolonged residence
      of the mucoadhesive tablets on human buccal mucosa for 8 to 13 h.

PMID- 15554224
TI  - Mucoadhesive delivery systems. II. Formulation and in-vitro/in-vivo evaluation of
      buccal mucoadhesive tablets containing water-soluble drugs.
AB  - From the previous work (Part I), mucoadhesive formulae containing 5% CP/65%
      HPMC/30% lactose and 2% PC/68% HPMC/30% mannitol as well as formulae based on
      sodium carboxymethyl cellulose (SCMC) were selected. Medicated tablets were
      prepared using diltiazem hydrochloride (DZ) and metclopramide hydrochloride (MP)
      in two different doses (30 and 60 mg). The effect of drug and dose on the
      mucoadhesive properties and in-vitro drug release was evaluated. All formulae
      produced extended drug release (over 8 to 12 h). Polyacrylic acid based matrices
      (PAA) showed Fickian's diffusion release pattern for both drugs. SCMC ensured
      zero-order release for DZ, which deviated to anomalous behavior in case of MP.
      Doubling the dose significantly reduced the bioadhesion strength (p<0.05) with a
      slight improvement in drug release rate. The formulation of bilayer tablets
      containing drug-free layer and medicated layer enhanced the drug release without
      affecting the bioadhesive performance. The bilayer tablet formulated with 2%
      PC/68% HPMC/30% mannitol (PC2) was selected for studying the in-vivo
      metoclopramide release in four healthy volunteers. The tablet ensured controlled
      drug release for 12 h, in addition, good correlation (r=0.9398) was observed
      between in-vitro and in-vivo data. The effect of ageing on selected formulae
      containing DZ and MP, respectively, was studied. Storage at 40 degrees C and 75%
      relative humidity for 6 months didn't influence the mucoadhesive performance,
      however, an enhanced released rate was observed.

PMID- 15554225
TI  - Review of the career of Professor Dr. Herbert Remmer.
AB  - This article is a laudatio summarizing the scientific career and accomplishments
      of Herbert Remmer as observed by one of his first students. The article traces
      over fifty years of multiple contributions of Herbert Remmer to pharmacology and
      toxicology and clearly identifies the leadership characteristics of this
      memorable man.

PMID- 15554226
TI  - Herbert Remmer during the early fifties, as seen by a doctoral fellow.
AB  - Herbert Remmer is remembered by his first Ph.D. student as a demanding mentor
      with high standards in scientific matters. Remmer was always ready to discuss and
      question his student's findings, and in this way, served as a lifetime model.
      Remmer was always generous with the multitude of scientific ideas he generated
      and he was ready to share these new ideas with others. Remmer is characterized as
      a person with universal interests possessing a curiosity in philosophy, religion
      and in all other unanswered questions of the universe.

PMID- 15554227
TI  - Personal remembrances of episodes in the life of Herbert Remmer.
AB  - Herbert Remmer was a wonderful friend and colleague. The present article recalls
      a number of episodes that occurred with the author in the 1960s and 1970s
      revealing the unique characteristics and idiosyncrasies of Herbert Remmer. He
      will be remembered as a special character who made seminal contributions to our
      knowledge of drug metabolism. There are only a few individuals with the
      dedication, interest, curiosity, and devotion to science of the caliber of
      Herbert Remmer.

PMID- 15554228
TI  - Remembering the good times: Herbert Remmer.
AB  - In the early 1970s, I experienced the joy of working in Tubingen, Germany with
      Herbert Remmer. The following brief description of events that occurred reflects
      personal impressions of those and subsequent interactions with Herbert Remmer. He
      will be remembered as a man blessed with a good humor, his interest in science
      and people, a philosophy of responsibility to his fellow man, and his enjoyment
      of life. The anecdotes presented here offer only a brief glimpse of this
      remarkable man.

PMID- 15554229
TI  - A photo-essay of the life and times of Herbert Remmer with his friends.
AB  - There are many wonderful memories one can relate about Herbert Remmer. He was a
      dedicated scientist, an excellent colleague, and a distinctive character in the
      international field of drug metabolism and toxicology. This article describes my
      first meeting in 1964 with Herbert Remmer. The article highlights his seminal
      contributions to our understanding of cytochrome P450 induction and the
      associated changes in the morphological contributions of the endoplasmic
      reticulum of the liver and the role of P450 as it relates to drug interactions as
      the initial step in drug metabolism. Also described are results of experiments
      carried out in 1964 when Herbert Remmer visited our laboratory at the Johnson
      Foundation of the University of Pennsylvania. It was these spectrophotometric
      experiments, showing spectral changes associated with the binding of drugs to
      liver microsomal P450 (with John Schenkman), that laid the foundation for our
      current understanding of the cyclic mechanism of P450 function during the
      metabolism of a great variety of xenobiotics. Herbert Remmer will be remembered
      as a frequent actor on the world stage of science. This article includes some of
      the many pictures I have in my files of Herbert Remmer and his friends as we
      traveled to exotic venues for scientific discussions of drug metabolism,
      toxicology, and risk assessment.

PMID- 15554230
TI  - Where is toxicology headed in the future?
AB  - Herbert Remmer was a pioneer in the study of the phenomenon of enzyme induction.
      He was also a leading figure, if not the foremost, in the development of the
      discipline of toxicology in Germany during his tenure as Professor of Toxicology
      at the University of Tubingen. Included here are some brief thoughts about where
      toxicology came from, where it is today, and what the future is. Toxicology is at
      a crossroads today, at an interface between basic science and applied projects.
      From its past as a descriptive discipline, it has incorporated a medley of
      concepts and technology from basic science. The usefulness of many approaches is
      now being evaluated. The hope is that toxicology will be able to be much more
      predictive in the future; a great need exists in the pharmaceutical industry. The
      shape of academic toxicology is also changing.

PMID- 15554231
TI  - The precautionary principle, toxicological science, and European-U.S. scientific
      cooperation.
AB  - Although it is an ages old concept, the precautionary principle is only a few
      decades old as a formal expression of a philosophy guiding protection of the
      environment and of human health. The emergence of the precautionary principle in
      the European Community and its relatively slower acceptance in the United States
      reflects differences in underlying social, cultural, and legal approaches to
      environmental and public health protection. Unfortunately, this poorly defined
      principle in some of its manifestations can lead to a loss of the toxicological
      scientific base that is necessary for short-term and long-term protection of the
      environment and public health. Examples of problems caused by using the
      precautionary principle include trade barriers erected by the European Community,
      and the loss of the impetus to develop understanding of the toxicity of hazardous
      air pollutants due to precautionary aspects of the 1990 U.S. Clean Air Act
      amendments. There are other U.S.-European differences in the organization and
      funding of science that are threatening the legacy of Herbert Remmer which was
      built on close trans-Atlantic scientific cooperation to the benefit of all.

PMID- 15554232
TI  - Rifampicin, a keystone inducer of drug metabolism: from Herbert Remmer's
      pioneering ideas to modern concepts.
AB  - In 1972, Herbert Remmer's group at the University of Tubingen had developed a
      micro method to assess cytochrome P450 contents and activities of drug
      metabolising enzymes in needle biopsies from human liver. Upon application of
      this method to patients receiving different kinds of drug therapy, Herbert Remmer
      was the first to describe that total human hepatic cytochrome P450 was markedly
      elevated by the new anti-tuberculosis drug rifampicin. Similar observations were
      made for the antimycotic clotrimazol. In 1975, Herbert Remmer's group described
      the unique species difference that induction of cytochrome P450 by rifampicin did
      not occur in the rat. After the first clinical reports of impaired effectiveness
      of oral contraception in persons treated with rifampicin, studies at Herbert
      Remmer's Institute showed a 4-fold increase, after repetitive rifampicin
      administration to humans, in the ability of hepatic microsomes to ortho
      hydroxylate the contraceptive estrogen ethinylestradiol, compared to microsomes
      from untreated normal subjects. Subsequent pharmacokinetic investigations were
      compatible with this induction of the estrogen-2-hydroxylase by rifampicin and
      provided a rational explanation for the classical drug interaction between
      rifampicin and oral contraceptives. These early studies, in the 1970s in
      Tubingen, were followed by further developments. It was realized that the
      cytochrome P450 isoenzyme 3A4 (CYP3A4) is the major CYP isozyme in the human
      liver metabolizing a variety of xenobiotics and endobiotics, being also
      responsible for the 2-hydroxylation of ethinylestradiol. The inducibility of
      CYP3A4 by barbiturates and rifampicin explains the effects of inducers to enhance
      the clearance of ethynylestradiol and thereby to reduce the effectiveness of oral
      contraceptives, rifampicin being one of the most potent inducers of human CYP3A4
      gene expression. Since 1998, novel "orphan" members of the nuclear hormone
      receptor superfamily were cloned from mouse, rat, rabbit, and human origin. These
      so-called pregnane X receptors (PXR), across species, are activated by inducers
      of CYP3A4 expression. It now appears that PXR is a key mediator of complex
      induction processes of xenobiotic processing enzymes, which are triggered by
      rifampicin and other inducers. Studies of the structure and substrate affinities
      of PXR have provided the rational explanation of the unique species difference of
      rifampicin induction between humans and rats that was first described by Herbert
      Remmer.

PMID- 15554233
TI  - The discovery of the microsomal ethanol oxidizing system and its physiologic and
      pathologic role.
AB  - Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic
      effects of ethanol but does not account for the tolerance. This fact, as well as
      the discovery of the proliferation of the smooth endoplasmic reticulum (SER)
      after chronic alcohol consumption, suggested the existence of an additional
      pathway which was then described by Lieber and DeCarli, namely the microsomal
      ethanol oxidizing system (MEOS), involving cytochrome P450. The existence of this
      system was initially challenged but the effect of ethanol on liver microsomes was
      confirmed by Remmer and his group. After chronic ethanol consumption, the
      activity of the MEOS increases, with an associated rise in cytochrome P450,
      especially CYP2E1, most conclusively shown in alcohol dehydrogenase negative deer
      mice. There is also cross-induction of the metabolism of other drugs, resulting
      in drug tolerance. Furthermore, the conversion of hepatotoxic agents to toxic
      metabolites increases, which explains the enhanced susceptibility of alcoholics
      to the adverse effects of various xenobiotics, including industrial solvents.
      CYP2E1 also activates some commonly used drugs (such as acetaminophen) to their
      toxic metabolites, and promotes carcinogenesis. In addition, catabolism of
      retinol is accelerated resulting in its depletion. Contrasting with the
      stimulating effects of chronic consumption, acute ethanol intake inhibits the
      metabolism of other drugs. Moreover, metabolism by CYP2E1 results in a
      significant release of free radicals which, in turn, diminishes reduced
      glutathione (GSH) and other defense systems against oxidative stress which plays
      a major pathogenic role in alcoholic liver disease. CYP1A2 and CYP3A4, two other
      perivenular P450s, also sustain the metabolism of ethanol, thereby contributing
      to MEOS activity and possibly liver injury. CYP2E1 has also a physiologic role
      which comprises gluconeogenesis from ketones, oxidation of fatty acids, and
      detoxification of xenobiotics other than ethanol. Excess of these physiological
      substrates (such as seen in obesity and diabetes) also leads to CYP2E1 induction
      and nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic fatty
      liver and nonalcoholic steatohepatitis (NASH), with pathological lesions similar
      to those observed in alcoholic steatohepatitis. Increases of CYP2E1 and its mRNA
      prevail in the perivenular zone, the area of maximal liver damage. CYP2E1 up
      regulation was also demonstrated in obese patients as well as in rat models of
      obesity and NASH. Furthermore, NASH is increasingly recognized as a precursor to
      more severe liver disease, sometimes evolving into "cryptogenic" cirrhosis. The
      prevalence of NAFLD averages 20% and that of NASH 2% to 3% in the general
      population, making these conditions the most common liver diseases in the United
      States. Considering the pathogenic role that up-regulation of CYP2E1 also plays
      in alcoholic liver disease (vide supra), it is apparent that a major therapeutic
      challenge is now to find a way to control this toxic process. CYP2E1 inhibitors
      oppose alcohol-induced liver damage, but heretofore available compounds are too
      toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an
      innocuous mixture of polyunsaturated phosphatidylcholines extracted from soybeans
      (and its active component dilinoleoylphosphatidylcholine), were discovered to
      decrease CYP2E1 activity. PPC also opposes hepatic oxidative stress and fibrosis.
      It is now being tested clinically.

PMID- 15554234
TI  - Xenobiotic metabolism and the mechanism(s) of benzene toxicity.
AB  - The investigation of the mechanism(s) of benzene toxicity/leukemogenesis over the
      past 50 years has been contemporaneous with developments in the study of
      xenobiotic metabolism. Research on the cytochrome P450 (CYP) enzyme system, and
      related systems in vivo and in vitro, which culminated in the isolation and
      reconstitution of the many CYPs, established pathways for the study of xenobiotic
      metabolism and its relationship to the biological activity of many chemicals. The
      essential role for metabolism of benzene as a precursor to the demonstration of
      benzene toxicity led to extensive studies of benzene metabolism, many of which
      will be reviewed here. Benzene toxicity/leukemogenesis, however, is a function of
      the bone marrow, a site remote from the liver where most benzene metabolism
      occurs. Studies of benzene metabolism have delineated the array of metabolites
      which appear to play a role in bone marrow damage, but further studies, both in
      vivo and in vitro, using appropriate animal models, will be needed to fully
      understand the impact of benzene and its metabolites on bone marrow function.

PMID- 15554235
TI  - Xenobiotic-metabolizing cytochromes P450 in ontogeny: evolving perspective.
AB  - While much is known about inducibility of the xenobiotic-metabolizing forms of
      cytochrome P450, the Family 1-3 enzymes, less well understood is the purpose for
      the presence of some of these forms in the developing conceptus. Many cytochrome
      P450 forms are present in the embryo and fetus, like the anabolic forms in
      Families 5 and higher, and are known to produce molecules with specific
      functions, e.g., cholesterol, steroids, and their metabolites necessary for
      normal physiological functions. As we gain greater understanding of the cell
      cycle and its regulation, and the roles of nuclear receptors in modulating
      transcriptional activities, a picture begins to emerge in which cytochrome P450
      forms appear as molecule-altering enzymes producing and eliminating ligands
      associated with nuclear receptor activities. For these CYP enzymes to exert a
      developmental action, a controlled spatial and temporal expression pattern would
      be essential. Studies now indicate the existence of such temporal control on the
      appearance of a number of these enzymes and the necessary coenzyme, NADPH
      cytochrome P450 reductase.

PMID- 15554236
TI  - Mitochondrial glutathione and chemically induced stress including ethanol.
AB  - The mechanisms of alcohol toxicity as related to mitochondrial dysfunction and
      the glutathione-dependent protective systems are reviewed. The pathophysiology of
      ethanol-induced liver damage is defined in terms of an early phase and a late
      phase. CYP2E1 dependent toxicity appears closely related to oxidative stress
      injury with possible roles of peroxynitrite, TNFalpha, protein adducts, and
      enhanced protein expression. Modulation of mitochondrial glutathione affects
      mitochondrial function and cell survival with superoxide and hydrogen peroxide
      generation being crucial to mitochondrial membrane permeability transition and
      apoptosis.

PMID- 15554237
TI  - Glutathione-dependent bioactivation of haloalkanes and haloalkenes.
AB  - Haloalkanes and haloalkenes constitute an important group of widely used
      chemicals that have the potential to induce toxicity and cancer. The toxicity of
      haloalkanes and haloalkenes may be associated with cytochromes P450- or
      glutathione transferase-dependent bioactivation. This review is concerned with
      the glutathione- and glutathione transferase-dependent bioactivation of
      dihalomethanes, 1,2-dihaloalkanes, and haloalkenes. Dihalomethanes, e.g.,
      dichloromethane, and 1,2-dihaloethanes, e.g., 1,2-dichloroethane and 1,2
      dibromoethane, undergo glutathione transferase-catalyzed bioactivation to give S
      (halomethyl)glutathione or glutathione episulfonium ions, respectively, as
      reactive intermediates. Haloalkenes, e.g., trichloroethene, hexachlorobutadiene,
      chlorotrifluoroethene, and tetrafluoroethene, undergo cysteine conjugate beta
      lyase-dependent bioactivation to thioacylating intermediates, including thioacyl
      halides, thioketenes, and 2,2,3-trihalothiiranes. With all of these compounds,
      the formation of reactive intermediates is associated with their observed
      toxicity.

PMID- 15554238
TI  - Coordinate regulation of drug metabolism by xenobiotic nuclear receptors: UGTs
      acting together with CYPs and glucuronide transporters.
AB  - Xenobiotic nuclear receptors (PXR, CAR, and the Ah receptor) coordinately induce
      genes involved in all phases of xenobiotic metabolism including oxidative
      metabolism, conjugation, and transport. The comment--dedicated to honor the
      memory of Herbert Remmer, mentor of the author K. W. B.--discusses mechanistic,
      functional, and evolutionary aspects of xenobiotic nuclear receptors which induce
      UGTs together with CYPs and glucuronide transporters in human and rodent liver
      and intestine. Recent findings on regulation of CYPs, UGTs, and transporters
      suggest that while nuclear receptor signaling induces different CYPs, regulation
      may converge on single UGTs and transporters. Functional consequences of co
      regulation are discussed using examples from the metabolism of xeno- and
      endobiotics (drugs, bilirubin, bile salts, steroid hormones, and carcinogens).
      Animal-plant interactions may have been a major driving force in the evolutionary
      divergence of CYPs and UGTs in mammals and insects as well as in their regulation
      by nuclear receptors. In addition, regulation by nuclear receptors was probably
      shaped by the need for homeostatic control of endobiotic signals in the evolution
      of multicellular organisms.

PMID- 15554239
TI  - Pharmacogenetics-based new therapeutic concepts.
AB  - Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic
      factors influence drug response. If hereditary traits are taken into account
      appropriately before starting drug treatment, the type of drug and its dosage can
      be tailored to the individual patient's needs. Pharmacogenetics adds a
      considerable amount of stringency to the doctor's therapeutic approach. Today, it
      is the relationship between dosage requirements and genetic variations in drug
      metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug
      transporters like p-glycoprotein, that is substantiated best. A standard dose
      will bring about more adverse effects than usual if enzymatic activity is lacking
      or feeble. Sometimes, however, therapeutic response might be better due to higher
      concentrations: proton pump inhibitors for eradication of Helicobacter pylori are
      more efficacious in carriers of a deficient CYP2C19 variant. The drug's
      interaction with its target (e.g. receptor) also depends on genetic factors. In
      some cases genetic tests can help distinguish between responders and non
      responders of a specific drug treatment. The first pharmacogenetic tests are
      already on the market.

PMID- 15554240
TI  - Quinone reductases multitasking in the metabolic world.
AB  - The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase)
      in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme
      involved in cellular defense against the electrophilic and oxidizing metabolites
      of xenobiotic quinones. It also participates in reduction of endogenous quinones,
      such as vitamin E quinone and ubiquinone, generating antioxidant forms of these
      molecules. NQO1 has recently been shown to interact with superoxide and may be
      involved in scavenging superoxide within the cell. In addition, the possible role
      of NQO1 in p53 stabilization and consequently in contributing to p53-dependent
      stress responses is summarized. Such protein multitasking is a good strategy in
      terms of cellular economy. NQO1 can also be exploited in the design of NQO1
      directed antitumor agents such as the new aziridinylbenzoquinone RH1 and Hsp90
      inhibitors such as 17AAG. Polymorphisms in NQO1 which have profound influence on
      phenotype such as the NQO1*2 polymorphism may influence the chemoprotective
      actions of NQO1, and should be considered when NQO1-directed antitumor quinones
      are used for therapy in patients.

PMID- 15554241
TI  - Isothiocyanates in cancer prevention.
AB  - Isothiocyanates are sulfur-containing compounds which are largely responsible for
      the typical flavor of cruciferous vegetables. In animals and humans they are
      conjugated with glutathione; the first product of this reaction is a
      dithiocarbamate, which can be ultimately metabolized to the corresponding
      mercapturic acid, excreted in urine. Aliphatic and aromatic isothiocyanates, as
      well as dithiocarbamates, can react quantitatively with an excess of 1,2
      benzenedithiol giving rise to a cyclic condensation product readily measured in
      biological fluids. The use of this assay as a biomarker of isothiocyanate or
      cruciferous vegetable intake can offer several advantages over food frequency
      questionnaires, mainly in the objectivity and accuracy of the measure and the
      lack of bias. Epidemiological studies on the relationship between cancer risk
      with isothiocyanate intake or excretion have shown inverse associations, mainly
      with lung cancer. The studies are also consistent in reporting a gene-environment
      interaction, with a stronger protective effect in persons null for the GSTM1 or
      GSTT1 genotype. However, further research is needed to better clarify the
      importance of these polymorphisms in modulating the effect of isothiocyanates in
      cancer development.

PMID- 15554242
TI  - The ABC transporters MDR1 and MRP2: multiple functions in disposition of
      xenobiotics and drug resistance.
AB  - ATP-binding cassette (ABC) transporters comprise one of the largest membrane
      bound protein families. They are involved in transport of numerous compounds.
      These proteins transport substrates against a concentration gradient with ATP
      hydrolysis as a driving force across the membrane. Mammalian ABC proteins have
      important physiological, pharmacological and toxicological functions including
      the transport of lipids, bile salts, drugs, toxic and environmental agents. The
      efflux pumps serve both as natural defense mechanisms and influence the
      bioavailability and disposition of drugs. In general terms, the transporters
      remove xenobiotics from the cellular environment. For example, in cancer cells,
      over expression of these molecules may confer to multidrug resistance against
      cytostatic drugs. In addition, based on diverse structural characteristics and a
      broad substrate specifity, ABC transport proteins alter the intracellular
      concentration of a variety of therapeutically used compounds and toxicologically
      relevant agents. We review the function of the human multidrug resistance protein
      MDR1, (P-glycoprotein, ABCB1) and the multidrug resistance protein MRP2 (ABCC2).
      We focus on four topics namely 1) structure and physiological functions of these
      transporters, 2) substrates e.g., drugs, xenotoxins, and environmental toxicants
      including their conjugates, 3) drug-drug interactions, and the role of
      chemosensitizers which may be able to reverse drug resistance, and 4)
      pharmacologically and toxicologically relevant genetic polymorphisms in transport
      proteins and their clinical implications.

PMID- 15554243
TI  - Detoxification of lithocholic acid, a toxic bile acid: relevance to drug
      hepatotoxicity.
AB  - Lithocholic acid, a monohydroxy, secondary bile acid, is formed by bacterial 7
      dehydroxylation of the primary bile acid chenodeoxycholic acid (CDCA) and of the
      secondary bile acid ursodeoxycholic acid (UDCA). Lithocholic acid and its
      precursor CDCA are toxic when fed to the rabbit, rhesus monkey, and baboon, but
      not when CDCA, as well as UDCA, is used for therapeutic purposes in man. Older
      studies showed that the species specific toxicity of lithocholic acid could be
      explained by efficient sulfation of lithocholic acid in man and in chimpanzee,
      but not in the rabbit, rhesus monkey, or baboon. Rodents detoxify lithocholic
      acid by hydroxylation, but this does not occur in species in which it is toxic.
      Recent studies suggest that lithocholic acid induces its own detoxification by
      activating nuclear receptors to promote transcription of genes encoding
      sulfotransferase. In addition, work with CaCo2 cells suggest that lithocholic
      acid may undergo sulfation in the enterocyte and be effluxed back into the
      intestinal lumen. The evolution of trihydroxy bile acids in vertebrates may have
      occurred to decrease the formation of lithocholic acid. Lithocholic acid is a
      rare example of a toxic endobiotic; a variety of mechanisms have evolved to solve
      the problem of efficient detoxification.

PMID- 15554244
TI  - The metabolic fate of amitriptyline, nortriptyline and amitriptylinoxide in man.
AB  - Amitriptyline (AT), the most widely used tricyclic antidepressant, undergoes
      oxidative metabolism in the side chain with production of the secondary amine
      nortriptyline (NT), a primary amine, and the N-oxide amitriptylinoxide (AT-NO);
      in addition, direct conjugation leads to a quaternary ammonium-linked
      glucuronide. Hydroxylation of AT or NT at the ethylene bridge of the central
      seven-membered ring results in four isomeric alcohols and occurs with high stereo
      and enantioselectivity, the (-)-(E)-10-hydroxy compounds usually being the major
      products. The disposition of the alcohols is also partially enantioselective, for
      instance with regard to glucuronidation and reversible oxidation to ketones.
      Introduction of a second hydroxy group results in isomeric glycols. Oxidative
      attack at an aromatic ring is a minor pathway leading to dihydrodiols and
      phenols. Numerous metabolites originate by combinations of reactions in the ring
      system and the side chain. AT-NO is by about one-third excreted in unchanged form
      or as 10-hydroxy derivative; the major part is reduced to AT and metabolized
      further. The review covers current knowledge on the enzymes participating in the
      individual pathways. Their quantitative importance is inferred from kinetic
      studies in volunteers and patients and from experiments in vitro. Clinical
      consequences of biochemical findings mainly derive from the impact of the
      polymorphic CYP2D6 mediating (-)-(E)-10-hydroxylation and from its potential
      inhibition by other psychoactive drugs.

PMID- 15554245
TI  - Antioxidant enzymes and apoptosis.
AB  - The role of antioxidant enzymes can be interpreted in terms of fine tuning of the
      concentration of reactive oxygen species which are required in the redox
      regulation of the cell cycle and of programmed cell death. This review summarizes
      findings from papers published in the last few years which deal with the relation
      between apoptosis and the two antioxidant enzymes, manganous superoxide dismutase
      (MnSOD) and catalase. With respect to MnSOD, the literature is much in favor of
      an inhibitory action in apoptosis. Increased MnSOD activity has been shown to
      prevent cell death via the receptor-mediated apoptotic pathway as well as cell
      death via the mitochondrial pathway. The literature on the influence of catalase
      activity on apoptosis is less consistent. Evidence for both an antiapoptotic and
      a proapoptotic role of catalase can be found. From the results reviewed here, two
      schemes for the involvement of MnSOD and catalase in the regulation of apoptosis
      can be extracted: 1) Both MnSOD and catalase inhibit apoptosis by removing
      superoxide anion radicals or H2O2, respectively, because these reactive oxygen
      species are mediators required for the apoptotic program or inhibit a survival
      pathway. 2) An increase in H2O2 by downregulation or inhibition of catalase
      activity and/or upregulation of MnSOD activity inhibits apoptosis while a
      decrease in H2O2 by upregulation of catalase activity and/or downregulation of
      MnSOD activity supports apoptosis, possibly because of a supportive role of H2O2
      in a survival pathway. The data reported so far do not allow for an explanation
      why some cell models appear to fit the first scheme while the second scheme
      appears to correctly describe other cell models. The present state of the
      literature reveals that antioxidant enzymes play a more intricate role in cell
      physiology than previously assumed.

PMID- 15554246
TI  - Organotin compounds: toxicokinetic aspects.
AB  - Organotin compounds have a broad range of applications. While dialkyltin
      compounds are used primarily as stabilizers for plastics, trisubstituted
      organotins are mainly used as biocides e.g., as an active ingredient of marine
      antifouling paints for boats and ships. Since a number of organotin compounds
      have been demonstrated to be toxic, there is increasing concern that their
      widespread use may cause adverse effects within environmental and biological
      systems. Besides carcinogenic and neurotoxic effects, as well as effects on the
      reproductive system, the most obvious mammalian effects of both various di- and
      trisubstituted organotins were found on the immune system. Exposure of humans to
      organotin compounds can take place through consumption of contaminated fish and
      seafood. In human liver samples, mainly dibutyltin, the metabolite of
      tributyltin, could be detected indicating that organotin compounds are
      bioavailable after dietary exposure. The objective of this short review is to
      present various toxicokinetic aspects of organotin compounds in more detail.
      While several studies using in vitro systems investigated their metabolism
      especially by the monooxygenase system, various aspects of absorption,
      distribution, metabolism, and excretion (ADME) pathways of different organotin
      compounds were described by data obtained from several studies with laboratory
      animals. However, most of these studies were not conducted as full ADME studies
      but dealt only with some of these aspects. Therefore, for definitive conclusions
      in some cases, additional information is requested. By reviewing and updating the
      current literature consideration was given preferentially to those organotin
      compounds which have relevance with respect to human exposure and/or
      toxicological effects.

PMID- 15554247
TI  - The "Tuebingen desiccator" system, a tool to study oxidative stress in vivo and
      inhalation toxicokinetics.
AB  - The "Tuebingen desiccator," a gas-tight all-glass closed chamber system (CCS),
      has been established in Herbert Remmer's Institute of Toxicology, University of
      Tuebingen, to investigate the mechanisms underlying the exhalation of endogenous
      volatile hydrocarbons in rats under oxidative stress. Remmer and associates
      confirmed the former view that ethane and n-pentane were derived from
      polyunsaturated fatty acids, and they demonstrated that propane, n-butane and
      isobutane were released from amino acids. Hydrocarbons exhaled following acute
      ethanol treatment of rats resulted predominantly from ethanol-dependent
      inhibition of their metabolism and partly from oxidation of proteins. Exhalation
      of alkanes in carbon tetrachloride exposed rats did not reflect liver damage,
      which was, however, directly linked to the amount of carbon tetrachloride
      metabolized. As has first been shown in Herbert Remmer's institute by
      investigating the fate of inhaled vinyl chloride in rats, the CSS proved to be
      also an excellent tool for studying toxicokinetics of inhaled gaseous xenobiotics
      by means of gas uptake experiments. Based on results gained by such studies, it
      was recently demonstrated that knowledge of compound-specific physicochemical and
      species-specific physiological parameters are often sufficient to predict
      important toxicokinetic properties of inhaled chemicals such as tissue burdens at
      steady state. By means of the CCS, not only kinetics of a parent gaseous
      substance but also of gaseous metabolites can be investigated in vivo, as
      exemplified for ethylene oxide and 1, 2-epoxy-3-butene, metabolites of ethylene
      and 1,3-butadiene, respectively. Gas uptake studies in closed chamber systems are
      now worldwide used for determining toxicokinetic parameters relevant for
      physiological toxicokinetic modeling.

PMID- 15554248
TI  - Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive
      oxygen/nitrogen species, and mitochondrial permeability transition.
AB  - Large doses of the analgesic acetaminophen cause centrilobular hepatic necrosis
      in man and in experimental animals. It has been previously shown that
      acetaminophen is metabolically activated by CYP enzymes to N-acetyl-p
      benzoquinone imine. This species is normally detoxified by GSH, but following a
      toxic dose GSH is depleted and the metabolite covalently binds to a number of
      different proteins. Covalent binding occurs only to the cells developing
      necrosis. Recently we showed that these cells also contain nitrated tyrosine
      residues. Nitrotyrosine is mediated by peroxynitrite, a reactive nitrogen species
      formed by rapid reaction between nitric oxide and superoxide and is normally
      detoxified by GSH. Thus, acetaminophen toxicity occurs with increased
      oxygen/nitrogen stress. This manuscript will review current data on acetaminophen
      covalent binding, increased oxygen/nitrogen stress, and mitochondrial
      permeability transition, a toxic mechanism that is both mediated by and leads to
      increased oxygen/nitrogen stress.

PMID- 15554249
TI  - Sulfonation in pharmacology and toxicology.
AB  - Sulfonation has a major function in modulating the biological activities of a
      wide number of endogenous and foreign chemicals, including: drugs, toxic
      chemicals, hormones, and neurotransmitters. The activation as well as
      inactivation of many xenobiotics and endogenous compounds occurs via sulfonation.
      The process is catalyzed by members of the cytosolic sulfotransferase (SULT)
      superfamily consisting of at least ten functional genes in humans. The reaction
      in intact cells may be reversed by arylsulafatase present in the endoplasmic
      reticulum. Under physiological conditions, sulfonation is regulated, in part, by
      the supply of the co-substrate/donor molecule 3'-phosphadensoine-5-phosphosulfate
      (PAPS), and transport mechanisms by which sulfonated conjugates enter and leave
      cells. Variation in the response of individuals to certain drugs and toxic
      chemicals may be related to genetic polymorphisms documented to occur in each of
      the above pathways. Sulfonation has a major function in regulating the endocrine
      status of an individual by modulating the receptor activity of estrogens and
      androgens, steroid biosynthesis, and the metabolism of catecholamines and
      iodothyronines Sulfonation is a key reaction in the body's defense against
      injurious chemicals and may have a major function during early development since
      SULTs are highly expressed in the human fetus. As with many Phase I and Phase II
      reactions, sulfonation may also serve as the terminal step in activating certain
      dietary and environmental agents to very reactive toxic intermediates implicated
      in carcinogenesis.

PMID- 15554250
TI  - Pharmacology, drug efficacy, and the individual.
AB  - The efficacy of drugs has to be demonstrated following the principal approach of
      statistical evaluation in controlled clinical trials. This scientifically and
      internationally accepted numerical approach has developed over the years to its
      importance, in contrast to the more pharmacologically attempt to extrapolate
      human efficacy of drugs from data obtained in animal experiments or, to the so
      called physiological medicine, which did not allow to delineate the suitability
      of drugs from a given collective to the individual patient. The requirements for
      the clinical trial are not always met, especially not with so-called surrogate
      markers. In addition, concerns exist now as ever that the numerically based
      approach leads to average drugs and information for the "responsible adult" only,
      to the debit of the individual patient. The concern does not mind the clinical
      trial as such, which principally can be tailored to the individual as applied
      with pharmacogenetics. On the other hand, an unbearable situation of increased
      efforts towards individualization, drug tailoring, and neglect of treatment for
      patients with neglected diseases, respectively, is immense. The contribution of
      the pharmacologists is, to present those detailed information which allow proper
      judgement for the clinical application of drugs for all patients.

PMID- 15554251
TI  - Functional divergency oriented synthesis of azoninones as the key intermediates
      for bioactive indolizidine alkaloids analogs.
AB  - A functional divergency oriented synthetic approach to the azoninone (9-membered
      lactams), key intermediate for the indolizidine alkaloids library, using amide
      enolate induced aza-Claisen rearrangement has been achieved.

PMID- 15554252
TI  - Synthesis and antifungal activity of 5,8-quinazolinedione derivatives modified at
      positions 6 and 7.
AB  - 5,8-Quinazolinediones modified at positions 6 and 7 were synthesized and tested
      for in vitro antifungal activities against Candida species and Aspergillus niger.
      Most of 5,8-quinazolinediones 3-5 generally exhibited potent antifungal activity.
      6-Arylamino-7-chloro-5,8-quinazolinediones (3) generally showed more potent
      antifungal activity than 7-arylthio-5,8-quinzolinediones (4) and 6,7-bis
      (arylthio)-5,8-quinazolinediones (5).

PMID- 15554253
TI  - Synthesis and in vitro cytotoxicity of- 1,3-dioxoindan-2-carboxylic acid
      arylamides.
AB  - A series of 1,3-dioxoindan-2-carboxylic acid arylamides were synthesized and
      evaluated for in vitro cytotoxicity against four human cancer cell lines (HOP62,
      SK-OV-3, MD-MB-468 and T-47D). The most active was compound 3e (1.2 microM
      against SK-OV-3 cell line) bearing a 4-methyl substituent.

PMID- 15554254
TI  - 3D QSAR studies on cinnamaldehyde analogues as farnesyl protein transferase
      inhibitors.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies
      on 59 cinnamaldehyde analogues as Farnesyl Protein Transferase (FPTase)
      inhibitors were investigated using comparative molecular field analysis (CoMFA)
      with the PLS region-focusing method. Forty-nine training set inhibitors were used
      for CoMFA with two different grid spacings, 2A and 1A. Ten compounds, which were
      not used in model generation, were used to validate the CoMFA models. After the
      PLS analysis, the best predictive CoMFA model showed that the cross-validated
      value (r2cv) and the non-cross validated conventional value (r2ncv) are 0.557 and
      0.950, respectively. From the CoMFA contour maps, the steric and electrostatic
      properties of cinnamaldehyde analogues can be identified and verified.

PMID- 15554255
TI  - Prediction on the chiral behaviors of drugs with amine moiety on the chiral
      cellobiohydrolase stationary phase using a partial least square method.
AB  - Quantitative Structure-Resolution Relationship (QSRR) using the Comparative
      Molecular Field Analysis (CoMFA) software was applied to predict the
      chromatographic behaviors of chiral drugs with an amine moiety on the chiral
      cellobiohydrolase (CBH) columns. As a result of the Quantitative CoMFA-Resolution
      Relationship study, using the partial least square method, prediction of the
      behavior of drugs with amine moiety upon chiral separation became possible from
      their three dimensional molecular structures. When a mixed mobile phase of 10 mM
      aqueous phosphate buffer (pH 7.0) - isopropanol (95:5) was employed, the best
      Quantitative CoMFA-Resolution Relationship, derived from the study, provided a
      cross-validated q2 = 0.933, a normal r2 = 0.995, while the best Quantitative
      CoMFA-Separation Factor Relationship, also derived from the study, yielded a
      cross-validated q2 = 0.939, a normal r2 = 0.991. When all of these results are
      considered, this QSRR-CoMFA analysis appears to be a very useful tool for the
      preliminary prediction on the chromatographic behaviors of drugs with an amine
      moiety inside chiral CBH columns.

PMID- 15554256
TI  - A new sesquiterpene lactone from Artemisia rubripes nakai.
AB  - The chromatographic separation of a methylene chloride extract of Artemisia
      rubripes led to the isolation of a new sesquiterpene lactone (3), together with
      four known compounds, a coumarin (2) and three terpenes (1, 4, and 5). Their
      structures were characterized to be 1beta,6alpha-dihydroxy-4(15)-eudesmene (1),
      scopoletin (2), 1alpha,4beta-dihydroxy-8alpha-acetoxy-guaia-2,10(14), 11(13)
      triene-6,12-olide (3), 1alpha,4beta-dihydroxy-8alpha-acetoxy-guaia-2,9,11(13)
      triene-6,12-olide (4), and beta-sitosterol-3-O-beta-D-glycoside (5) by
      spectroscopic means.

PMID- 15554257
TI  - New ceramide from Alocasia macrorrhiza.
AB  - A new ceramide alomacrorrhiza A was isolated from the ethanolic extract of the
      plant Alocasia macrorrhiza (L.) Schott. Its chemical structure was elucidated as
      (2S,3S,4R)-2N-[(2'R)-2'-hydroxy-hexacosanoyl]-tetradecane-1,3,4-triol based on
      extensive 1D, 2D NMR, EI-MS, FAB-MS, HR-FAB-MS spectroscopic data and chemical
      degradation studies.

PMID- 15554258
TI  - Flavonoids from Iris spuria (Zeal) cultivated in Egypt.
AB  - A new 12a-dehydrorotenoid 1, 11-dihydroxy-9, 10-methylenedioxy-12a
      dehydrorotenoid (1), together with a new isoflavonoid glycoside tectorigenin-7-O
      beta-glucosyl-4'-O-beta-glucoside (3), were isolated and identified from the
      rhizomes of I. spuria (Zeal). In addition, 4 known compounds, tectorigenin (2)
      tectorigenin-7-O-beta-glucosyl (1 --> 6) glucoside (4), tectoridin (a
      tectorigenin-7-O-beta-glucoside) (5) and tectorigenin-4'-O-beta-glucoside (6)
      were isolated and identified for the first time from this plant. The structures
      of the isolated compounds were determined by spectroscopic methods (UV, IR, 1H,
      13C-NMR, DEPT, HMQC, NOESY, and HMBC experiments and MS spectrometry) and by
      comparison with literature data of known compounds. Compounds 2, 4, 5, and 6 are
      reported for the first time from this plant through the present study.

PMID- 15554259
TI  - Phytochemical constituents of Carpesium macrocephalum F(R). et S(AV).
AB  - From the methanol extract of the whole plants of Carpesium macrocephalum F(R). et
      S(AV)., five sesquiterpene lactones (1: carabron, 2: tomentosin, 3: ivalin, 4: 4H
      tomentosin, 5: carabrol) and three terpenoids (6: loliolide, 7: vomifoliol, 8:
      citrusin C) were isolated. The structures and stereochemistry of compounds 1-8
      were established on the basis of chemical analysis as well as 1D- and 2D-NMR
      spectroscopy. Among them, compounds 2, 4, and 6-8 were isolated for the first
      time from Carpesium species.

PMID- 15554260
TI  - Constituents of the halophyte Salicornia herbacea.
AB  - Four compounds were isolated from Salicornia herbacea by repeated column
      chromatography. Their structures were identified as beta-sitosterol (1),
      stigmasterol (2), uracil (3), and isorhamnetin-3-O-beta-D-glucopyranoside (4) by
      spectral analysis and comparison with the published data.

PMID- 15554261
TI  - Hypotensive and toxicological study of citric acid and other constituents from
      Tagetes patula roots.
AB  - Study of the effects of the methanolic extract of Tagetes patula roots on blood
      pressure led to the isolation of well known citric (1) and malic acid (7) as
      hypotensive, and pyridine hydrochloride (4) as hypertensive constituents of the
      plant along with a new constituent, 2-hydroxy, 5-hydroxymethyl furan (9). Citric
      acid and malic acid caused 71% and 43% fall in Mean Arterial Blood Pressure
      (MABP) of rats at the doses of 15 mg/kg and 30 mg/kg respectively while pyridine
      hydrochloride produced 34% rise in the MABP of rats at the dose of 30 mg/kg. LD50
      and LD100 of citric acid in mice have been determined as 545 mg/kg and 1000
      mg/kg, respectively.

PMID- 15554262
TI  - Inhibition of phospholipase Cgamma1 and cancer cell proliferation by lignans and
      flavans from Machilus thunbergii.
AB  - Thirteen compounds were isolated from the CH2Cl2 fraction of Machilus thunbergii
      as phospholipase Cgamma1 (PLCgamma1) inhibitors. These compounds were identified
      as nine lignans, two neolignans, and two flavans by spectroscopic analysis. Of
      these, 5,7-di-O-methyl-3',4'-methylenated (-)-epicatechin (12) and 5,7,3'-tri-O
      methyl (-)-epicatechin (13) have not been reported previously in this plant. In
      addition, seven compounds, machilin A (1), (-)-sesamin (3), machilin G (5), (+)
      galbacin (9), licarin A (10), (-)-acuminatin (11) and compound 12 showed dose
      dependent potent inhibitory activities against PLCgamma1 in vitro with IC50
      values ranging from 8.8 to 26.0 microM. These lignans, neolignans, and flavans
      are presented as a new class of PLCgamma1 inhibitors. The brief study of the
      structure activity relationship of these compounds suggested that the benzene
      ring with the methylene dioxy group is responsible for the expression of
      inhibitory activities against PLCgamma1. Moreover, it is suggested that
      inhibition of PLCgamma1 may be an important mechanism for an antiproliferative
      effect on the human cancer cells. Therefore, these inhibitors may be utilized as
      cancer chemotherapeutic and chemopreventive agents.

PMID- 15554263
TI  - Determination of the kinetic properties of platycodin D for the inhibition of
      pancreatic lipase using a 1,2-diglyceride-based colorimetric assay.
AB  - A 1, 2-diglyceride-based multi-step colorimetric assay to measure the pancreatic
      lipase activity was applied for the determination of the kinetic profiles of the
      lipase inhibition with a slight modification and the validity verification. With
      this assay method, our study revealed that platycodin D, one of major
      constituents of Platycodi Radix, inhibits the pancreatic lipase activity in a
      competitive type, with the value of Kl being 0.18 +/- 0.02 mM. In addition, PD
      has affected the values of Km,app and Kcat/Km in a dose- dependent manner. The
      results shed a meaningful light on how PD mediates lipid metabolism in the
      intestinal tracts. On the other hand, since the revised assay is sensitive,
      rapid, and does not affect the accuracy to the kinetic properties, it is
      applicable not only to evaluation of the kinetic properties of the pancreatic
      lipase, but also to high-throughput screening of pancreatic lipase activity.

PMID- 15554264
TI  - Anti-inflammatory effects of N1-benzyl-4-methylbenzene-1,2-diamine (JSH-21)
      analogs on nitric oxide production and nuclear factor-kappa B transcriptional
      activity in lipopolysaccharide-stimulated macrophages RAW 264.7.
AB  - N1-Benzyl-4-methylbenzene-1,2-diamine (JSH-21) and its analogs were chemically
      synthesized and their anti-inflammatory potentials investigated. JSH-21 inhibited
      nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages
      RAW 264.7 in a dose-dependent manner, with an IC50 value of 9.2 microM, where
      pyrrolidine dithiocarbamate and parthenolide as positive controls exhibited IC50
      values of 29.3 and 3.6 microM, respectively. The inhibitory effect of JSH-21 on
      the NO production was attributable to its down-regulatory action on LPS-inducible
      NO synthase (iNOS), which was documented by iNOS promoter activity. In the
      mechanism of the anti-inflammatory action, JSH-21 exhibited inhibitory effects on
      LPS-induced DNA binding activity and transcriptional activity of nuclear factor
      kappa B (NF-kappaB). Structural analogs of JSH-21 also inhibited both the LPS
      induced NO production and NF-kappaB transcriptional activity, where diamine
      substitution at positions 1 and 2 of JSH-21 seems to play an important role in
      the anti-inflammatory activity.

PMID- 15554265
TI  - Triterpenoid from Tiarella polyphylla, regulation of type 1 procollagen and MMP-1
      in ultraviolet irradiation of cultured old age human dermal fibroblasts.
AB  - Although many studies have been performed to elucidate the molecular consequences
      of ultraviolet irradiation, little is known about the effect of natural products.
      Ultraviolet irradiation is widely considered to be an environmental stress. Here
      we investigated the effect of 3,23-dihydroxy-20(29)-lupen-27-oic acid on the
      regulation of MMP-1 and type 1 procollagen in Ultraviolet irradiation of cultured
      old age human dermal fibroblasts. 3, 23-dihydroxy-20(29)-lupen-27-oic acid was
      isolated from Tiarella polyphylla D. Don (Saxifragaceae). Among them, 3, 23
      dihydroxy-20(29)-lupen-27-oic acid induced the regulation of Type 1- procollagen
      and reduced the regulation of MMP-1 at the protein levels in a dose-dependent
      manner by ultraviolet irradiation. Taken together, our results suggest that 3, 23
      dihydroxy-20(29)-lupen-27-oic acid plays an important role in the induction of
      Type 1-procollagen and reduction of MMP-1 by ultraviolet irradiation in old age
      human dermal fibroblasts.

PMID- 15554266
TI  - Nelumbinis Semen reverses a decrease in 5-HT1A receptor binding induced by
      chronic mild stress, a depression-like symptom.
AB  - Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5
      HT) system. More recently, several lines of evidence suggest that an important
      factor in the development of depression may be a deficit in the function and
      expression of 5-HT1A receptors. The present study assessed if Nelumbinis Semen
      (N.s.) had an anti-depression effect through reversing a decrease in 5-HT1A
      receptor binding in rats with depression-like symptoms induced by chronic mild
      stress. Using a 5-HT1A receptor binding assay, with a specific 5-HT1A receptor
      agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of
      the anti-depression effect of N.s. on rats was investigated, and the effects
      compared with two well-known antidepressants, Hyperium Perforatum (St. Johns
      Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal
      (N) group without chronic mild stress (CMS), the control (C) group under CMS for
      8 weeks, the Nelumbinis Semen (N.s.) treatment group under CMS for 8 weeks, the
      Hyperium Perforatum (H.p.) treatment group under CMS for 8 weeks and finally, the
      fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was
      administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake
      test was performed to test the anti-depression effect of N.s. The N.s. treatment
      significantly reversed the decreased sucrose intake under CMS (P < 0.05 compared
      to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both
      N.s. and H.p. reversed the CMS-induced decrease in 5-HT1A receptor binding. In
      the I to II regions of the frontal cortex, N.s. and H.p. also reversed the CMS
      induced decrease in 5-HT1A receptor binding, and even showed a significant
      increase in 5-HT1A receptor binding compared to the F treatment group (N.s. vs.
      P, p < 0.05, H.p. vs. P, p < 0.05). However, in the hypothalamus, all treatments
      reversed the CMS-induced decrease in 5-HT1A receptor binding. This reversal
      effect of N.s. on the decrease in 5-HT1A receptor binding in the frontal cortex,
      hippocampus and hypothalamus of rat brains was very similar to that of H.p, but
      different from that of F. It is concluded that N.s. presents an anti-depression
      effect through enhancing 5-HT1A receptor binding.

PMID- 15554267
TI  - Vitamin C blocks TNF-alpha-induced NF-kappaB activation and ICAM-1 expression in
      human neuroblastoma cells.
AB  - Interactions of the cell adhesion molecules are known to play important roles in
      mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-alpha
      (TNF-alpha), activates the NF-kappaB signaling pathway, which induces the
      expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1).
      In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF
      alpha in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment
      with vitamin C resulted in the downregulation of the TNF-alpha-induced surface
      expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover,
      a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF
      kappaB activation and IkappaBalpha degradation induced by TNF-alpha. Taken
      together, these results suggest that vitamin C downregulates TNF-alpha-induced
      ICAM-1 expression via the inhibition of NF-kappaB activation.

PMID- 15554268
TI  - Surgical education in the 21st century: hit or miss?

PMID- 15554269
TI  - Time management in the operating room: an analysis of the dedicated minimally
      invasive surgery suite.
AB  - BACKGROUND: Dedicated minimally invasive surgery suites are available that
      contain specialized equipment to facilitate endoscopic surgery. Laparoscopy
      performed in a general operating room is hampered by the multitude of additional
      equipment that must be transported into the room. The objective of this study was
      to compare the preparation times between procedures performed in traditional
      operating rooms versus dedicated minimally invasive surgery suites to see whether
      operating room efficiency is improved in the specialized room. METHODS: The
      records of 50 patients who underwent laparoscopic procedures between September
      2000 and April 2002 were retrospectively reviewed. Twenty-three patients
      underwent surgery in a general operating room and 18 patients in an minimally
      invasive surgery suite. Nine patients were excluded because of cystoscopic
      procedures undergone prior to laparoscopy. Various time points were recorded from
      which various time intervals were derived, such as preanesthesia time, anesthesia
      induction time, and total preparation time. A 2-tailed, unpaired Student t test
      was used for statistical analysis. RESULTS: The mean preanesthesia time was
      significantly faster in the minimally invasive surgery suite (12.2 minutes)
      compared with that in the traditional operating room (17.8 minutes) (P=0.013).
      Mean anesthesia induction time in the minimally invasive surgery suite (47.5
      minutes) was similar to time in the traditional operating room (45.7 minutes)
      (P=0.734). The average total preparation time for the minimally invasive surgery
      suite (59.6 minutes) was not significantly faster than that in the general
      operating room (63.5 minutes) (P=0.481). CONCLUSION: The amount of time that
      elapses between the patient entering the room and anesthesia induction is
      statically shorter in a dedicated minimally invasive surgery suite. Laparoscopic
      surgery is performed more efficiently in a dedicated minimally invasive surgery
      suite versus a traditional operating room.

PMID- 15554271
TI  - Laparoscopy in complicated pediatric appendicitis.
AB  - BACKGROUND: Complicated appendicitis (gangrenous or perforated) has been
      associated with increased risk for postoperative complications, especially
      intraabdominal abscess. Caution has been advised when attempting laparoscopic
      appendectomy for complicated appendicitis in children. The objective of our study
      was to assess the incidence of intraabdominal abscess formation after
      laparoscopic appendectomy in pediatric patients presenting with complicated
      appendicitis. METHODS: This is a retrospective review of 52 pediatric patients
      presenting with acute appendicitis at a single teaching institution who underwent
      laparoscopic appendectomy by a single surgeon. All laparoscopic procedures were
      completed without conversion. Treatment complications and outcomes were recorded
      for all cases. RESULTS: Five of the 52 patients (10%) had complicated
      appendicitis. One of the 5 patients (20%) developed intraabdominal abscess
      postoperatively and underwent laparoscopic drainage during the same admission. No
      other complications were noted. None of these patients was readmitted for wound
      infections or intraabdominal abscesses. The single postoperative abscess occurred
      early during our initial experience with laparoscopic appendectomy. CONCLUSION:
      Laparoscopic appendectomy seems to be a safe alternative for the treatment of
      complicated appendicitis in children. Caution is recommended during the initial
      experience of surgeons with this procedure, because the complication rate seems
      to be higher during the learning curve. Close postoperative follow-up and a high
      index of suspicion for development of complications is recommended. As surgeons'
      experience accumulates, the safety of the procedure seems to increase. A
      prospective, randomized trial is recommended to establish the role of laparoscopy
      in complicated appendicitis in the pediatric population.

PMID- 15554270
TI  - The role of laparoscopy in penetrating abdominal trauma.
AB  - BACKGROUND: Minimally invasive surgery has become increasingly utilized in the
      trauma setting. When properly applied, it offers several advantages, including
      reduced morbidity, lower rates of negative laparotomy, and shortened length of
      hospital stay. The purpose of this study was to evaluate the role of laparoscopy
      in the management of trauma patients with penetrating abdominal injuries.
      METHODS: We conducted a 3-year retrospective chart review of 4541 trauma patients
      admitted to our urban Level II trauma center. Penetrating abdominal injuries
      accounted for 209 of these admissions. Patients were divided into 3 treatment
      groups based on the characteristics of their abdominal injuries. Management was
      either observation, immediate laparotomy, or screening laparoscopy. RESULTS:
      Thirty-three patients were observed in the Emergency Department based on their
      initial physical examination and radiologic studies. After Emergency Department
      evaluation, 154 patients underwent immediate laparotomy. In this group, 119
      therapeutic laparotomies, 11 nontherapeutic laparotomies, and 24 negative
      laparotomies were performed. A review of the negative laparotomies revealed that
      possibly 8 of 10 gun shot wounds and all 14 stab wounds could have been done
      laparoscopically. Twenty-two patients underwent laparoscopic evaluation, 9 of
      which were converted to open procedures. CONCLUSION: Minimally invasive surgical
      techniques are particularly helpful as a screening tool for anterior abdominal
      wall wounds and lower chest injuries to rule out peritoneal penetration.
      Increased use of laparoscopy in select patients with penetrating abdominal trauma
      will decrease the rate of negative and nontherapeutic laparotomies, thus lowering
      morbidity and decreasing length of hospitalization. As technology and expertise
      among surgeons continues to improve, more therapeutic intervention may be done
      laparoscopically in the future.

PMID- 15554272
TI  - Laparoscopic adrenalectomy for isolated adrenal metastasis.
AB  - BACKGROUND: Laparoscopic adrenalectomy is accepted by many as the standard of
      care for the majority of adrenal masses less than 8 cm. The question exists
      whether laparoscopic removal of metastatic lesions to the adrenal is more
      difficult than laparoscopic removal of primary adrenal lesions. METHODS: We
      performed a retrospective analysis of all laparoscopic adrenalectomies performed
      at a single institution from 1998 to 2001, comparing laparoscopic adrenalectomies
      for primary lesions of the adrenal gland versus isolated metastatic lesions to
      the adrenal gland. RESULTS: Fourteen laparoscopic adrenalectomies were attempted,
      10 for primary disease and 4 for metastatic disease. All 10 laparoscopic
      procedures were completed successfully for primary disease (average operative
      time=218 minutes, average tumor size=4 cm, median hospital stay=2 days). Only one
      of the 4 laparoscopic adrenalectomies for metastatic disease was completed
      successfully (average operative time=332 minutes, average tumor size=7.3 cm,
      median hospital stay=2 days). No major complications occurred in either group.
      CONCLUSIONS: We feel laparoscopic adrenalectomy is the preferred approach for
      primary adrenal masses less than 8 cm. Based on our experience and a review of
      the literature, isolated metastatic lesions to the adrenal gland appear less
      amenable to laparoscopic removal than do primary lesions of the same size.

PMID- 15554274
TI  - Making the transition from standard gynecologic laparoscopy to robotic
      laparoscopy.
AB  - OBJECTIVES: To determine the feasibility of using a simple procedure, a bilateral
      tubal ligation, as a transition procedure when adopting robotic laparoscopy for
      gynecologic surgery. METHOD: To obtain robotic credentialing and gain experience
      with the robotic system, the surgeons first went through robotic training, then 4
      women desiring permanent sterilization had robotically assisted laparoscopic
      bilateral tubal ligations performed, using the Parkland method. RESULTS: Total
      operating room time varied from 1 hour 25 minutes to 2 hours 31 minutes.
      Improvement in operating time for each surgeon was noted with each successive
      case. Best times in robotic cases were similar to those of standard laparoscopy.
      CONCLUSION: Robotically assisted laparoscopic tubal ligation using the Parkland
      method is a satisfactory procedure to provide transition for gynecologic surgeons
      and operating room personnel to gynecologic robotic surgery.

PMID- 15554273
TI  - Outcome of patients undergoing laparoscopic adrenalectomy for primary
      hyperaldosteronism.
AB  - OBJECTIVES: To study the long-term outcome of patients with primary
      hyperaldosteronism who underwent laparoscopic adrenalectomy and to determine the
      preoperative predictive factors of persistent hypertension. METHODS: Between 1996
      and 2002, 47 patients with primary hyperaldosteronism underwent transperitoneal
      laparoscopic adrenalectomy at our institution. Their clinical and biochemical
      parameters were reviewed retrospectively, and the outcome of 46 patients with
      complete follow-up notes were determined. RESULTS: The study comprised 16 male
      and 30 female patients with a mean age of 45.6 years (range, 18 to 63 years).
      Almost all patients had hypertension and hypokalemia at presentation, requiring
      medication. The average operating time was 127 minutes (range, 70 to 240 min),
      and the mean postoperative stay was 2.6 days (range, 1 to 5 days). No mortalities
      occurred, and perioperative morbidity was minimal. Forty-two (91%) patients had
      adrenal cortical adenoma (including 1 with both adenoma and hyperplasia), and 4
      (9%) had adrenal hyperplasia on histology. The average follow-up time was 21
      months (range, 1 to 60 months), and at the end of follow-up, all patients had
      normal serum potassium levels without potassium supplements. Twenty-three (50%)
      patients were cured of hypertension, and 13 (28%) patients had better control of
      their hypertension as evidenced by the decrease in the number of antihypertensive
      medications used. On multivariate analysis, the age of the patient at surgery was
      shown to be an independent predictive factor of persistent hypertension after
      successful surgery. CONCLUSION: Laparoscopic adrenalectomy is a safe and
      effective way to treat primary hyperaldosteronism, especially in controlling
      hypokalemia and in the management of hypertension. The age of a patient at
      surgery is an independent preoperative risk factor of persistent hypertension.

PMID- 15554275
TI  - Interstitial cystitis in persistent posthysterectomy chronic pelvic pain.
AB  - OBJECTIVES: Hysterectomies may be performed unnecessarily in women with chronic
      pelvic pain if the diagnosis of interstitial cystitis is not considered. The
      objectives of this study were to investigate the prevalence of interstitial
      cystitis in patients with posthysterectomy chronic pelvic pain and to evaluate
      the efficacy of various therapies for interstitial cystitis. METHODS: A study was
      performed of 111 patients with chronic pelvic pain whose pain persisted after
      hysterectomy. Patients were screened with the Pelvic Pain and Urgency/Frequency
      symptom scale, and underwent Potassium Sensitivity Testing. Patients were treated
      with dietary changes alone or in combination with cystoscopic hydrodistention or
      oral pentosan polysulfate, or both of these, for 3 to 6 months. RESULTS: Of the
      111 patients enrolled, 79% (n=88) were diagnosed with bladder dysfunction
      consistent with interstitial cystitis. For patients treated with dietary
      modification alone (n=33), the mean score on the Pelvic Pain and
      Urgency/Frequency questionnaire improved 15.4%, from 13.18 at baseline to 11.15
      at follow-up. For patients treated with pentosan polysulfate or cystoscopic
      hydrodistention, or both, plus diet changes (n=78), Pelvic Pain and
      Urgency/Frequency scores improved 34.2%, from 15.01 to 9.87. CONCLUSION: In this
      study, nonsurgical treatment for interstitial cystitis resulted in a marked
      improvement in symptoms that had not improved with surgery. Without determining
      the origin of bladder pain, gynecologists should not proceed to hysterectomy in
      patients with chronic pelvic pain.

PMID- 15554276
TI  - Experience of laparoscopic tubal surgery at the department of obstetrics and
      gynecology, University of Kiel, from 1999 through 2000.
AB  - OBJECTIVE: We analyzed the results of laparoscopic tubal surgery performed at the
      Department of Obstetrics and Gynaecology, University of Kiel, between 1999 and
      2000. A retrospective review of 236 tubal surgical procedures was conducted: (1)
      patients with ectopic pregnancies, unilateral or bilateral tubal occlusions or
      alterations and (2) medically indicated sterilizations and salpingectomies.
      METHODS: Two specialists and 10 gynecologists in residency training performed the
      following 236 procedures: 64 salpingotomies, 74 salpingectomies, 25
      salpingostomies, 8 tubal end-to-end anastomoses, 24 fimbrioplasties, and 41 tubal
      sterilizations. In June 2001, questionnaires were sent to all 236 patients who
      underwent laparoscopic tubal surgery to evaluate subsequent pregnancies. From the
      195 answers received, 155 patients wished to have children and of these 79 (51%)
      became pregnant. In 8 tubal reversals, 6 pregnancies occurred, resulting in a 75%
      success rate. In the group of sterilizations and salpingectomies, no pregnancies
      occurred. RESULTS: A pregnancy rate of 51% resulted after tubal reconstructive
      surgery. After tubal sterilization, no pregnancies were observed in the following
      3 years. CONCLUSION: Laparoscopic tubal surgery has surpassed laparotomic tubal
      surgery with comparable success rates. Laparoscopic tubal surgery is also a less
      traumatic procedure.

PMID- 15554277
TI  - Laparoscopic assistance after vaginal hysterectomy and unsuccessful access to the
      ovaries or failed uterine mobilization: changing trends.
AB  - OBJECTIVES: We conducted retrospective and prospective clinical studies at the
      Columbus Hospital of Rome to point out changes in choosing the route for
      performing hysterectomy; to evaluate the feasibility of vaginal hysterectomy (VH)
      and oophorectomy, even in commonly considered contraindications to the vaginal
      route; to describe a method of laparoscopic oophorectomy following vaginal
      hysterectomy; and laparoscopic assistance in impossible vaginal hysterectomies.
      METHODS: From November 1999 to November 2001, 226 patients (age 46.1+/-4.6 years,
      range 35 to 58) underwent hysterectomy for benign pathologies: 22 (9.7%)
      underwent total laparoscopic hysterectomy for the presence of severe
      endometriosis, limited access to the fornices, or immobile uterus with no lateral
      mobilization; 204 (90.3%) underwent vaginal hysterectomy. Patients with uterine
      prolapse were excluded. Uterine size, previous cesarean deliveries, pelvic
      surgeries and the requirement of prophylactic oophorectomy were not considered
      contraindications to the vaginal approach. We retrospectively analyzed 509
      hysterectomies performed in the previous 2 years from 1997 through 1998. RESULTS:
      During vaginal hysterectomy, adnexectomy was possible in 90.6% of the cases in
      which it was indicated (unilateral in 21.8% because of adnexal pathology) and was
      technically impossible in 9.3%. In 4 patients (1.9%), it was not possible to
      complete a vaginal hysterectomy, owing to the presence of thick adhesions
      obliterating the cul-de-sac, to severe endometriosis, or to other unforeseen
      circumstances. In these few patients with difficult access to the ovaries (2.9%
      of all VH) or with difficulties in mobilizing the uterus, we resorted to
      laparoscopy. The pneumoperitoneum was achieved with an insufflation tube inserted
      via the vagina into the abdominal cavity and packing the vagina. Thus, the risks
      associated with the insertion of the Veress needle were avoided. In all but 2
      patients in whom conversion to laparotomy was necessary, laparoscopy was
      successfully completed. No major complications occurred. In the retrospective
      analysis of 509 hysterectomies, we determined that 29% were vaginal, 43%
      abdominal, and 28% laparoscopic (mostly LAVH). In the following years, LAVH
      allowed the conversion of a significant number of abdominal or laparoscopic
      hysterectomies to a vaginal route, showing that the vaginal approach was possible
      in most of cases. CONCLUSIONS: The vaginal approach is feasible in more than 90%
      of cases even if oophorectomy is required. In the few cases with difficult access
      to ovaries or difficulties in mobilizing the uterus, the laparoscopic route can
      easily be adapted by packing the vagina and obtaining a pneumoperitoneum without
      the risk and loss of time of the insertion of the Veress needle. In this way, it
      is possible to avoid a great number of LAVH, reducing operating time and the
      risks of a concomitant procedure.

PMID- 15554278
TI  - A new device for sentinel node detection in laparoscopic colon resection.
AB  - OBJECTIVE: To test the feasibility of using a newly developed device for
      laparoscopic lymphatic mapping of the colon by simultaneous and quantitative
      detection of both tissue coloration and radioactivity. METHODS: Four pigs were
      used in this study. In each animal, both blue dye and radioisotope injections
      were utilized. Lymphatic mapping was performed laparoscopically in the sigmoid
      mesocolon and in the right mesocolon. A solution containing a mix of 35
      microcuries of Technetium Tc-99 sulfur Colloid and 1 mL of a vital blue dye was
      administered subserosally by percutaneous insertion of a 25 gauge needle under
      laparoscopic control. The new device for automated sentinel-node detection
      consists of a gamma-probe coupled with a laser device and can be passed through a
      regular 10-mm trocar. The device detects simultaneously both radioactivity and
      quantitative tissue coloration. Nodes showing a radioactivity at least 5 times
      higher than that of the background or that had a blue colorant concentration were
      considered our sentinel nodes. RESULTS: Laparoscopic simultaneous and
      quantitative detection of sentinel nodes was feasible in all pigs. One or more
      sentinel nodes were identified by either the blue dye or radioisotopic technique
      in both the sigmoid and right mesocolon. Quantitative tissue coloration detection
      led to the recognition of additional nodes that were not apparently colored to
      the naked eye. CONCLUSION: Laparoscopic sentinel node detection using a device
      combining gamma and color detection is feasible in the porcine model. The
      significance of nodes apparently clear but positive with the quantitative
      detection technique should be further evaluated.

PMID- 15554279
TI  - Lifting of the colon for laparoscopic-assisted colectomy for colon and rectal
      cancer.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic-assisted colectomy for colon and rectal
      cancer causes less surgical trauma than does open colectomy. However, current
      methods are more costly and require highly skilled staff. In addition, the
      technique for lymphadenectomy has yet to be standardized. We developed a
      technique that uses a nylon suture to elevate the colon. This method reduces
      costs without compromising the completeness of the resection. METHODS: Three
      trocars are introduced and a 1-0 nylon suture is passed into the abdominal cavity
      and through the mesocolon. The colon is retracted anteriorly and is fixed by this
      suture to the abdominal wall. The main mesenteric vessels are under tension, and
      lymph node dissection is performed easily. This method requires only 2 surgeons,
      an operator, and a scopist, because the colon is fixed to the abdominal wall. In
      addition, the working space is more stable because the colon is fixed to the
      abdominal wall. The procedure is relatively independent of the skill of the first
      assistant. RESULTS: From April 2000 to August 2002, this method was performed in
      52 patients. The mean number of dissected lymph nodes was 16.9+/-9.0 (range, 6 to
      41). Nine patients had lymph node metastases (17.3%). One patient developed
      hepatic recurrence; all patients are alive. No complication occurred that was
      related to lifting the colon. CONCLUSIONS: Using a suture to lift the colon is a
      useful method for performing laparoscopic-assisted colectomy with
      lymphadenectomy. This method reduces the number of surgical staff and the expense
      of the procedure.

PMID- 15554280
TI  - The laparoscopic management of benign bowel fistulas.
AB  - BACKGROUND: The presence of a fistula has usually been a factor predicting high
      conversion and complication rates following laparoscopic procedures for Crohn's
      disease and diverticulitis. METHODS: We studied retrospective data collected from
      the medical case notes of patients. A single surgeon carried out all these
      procedures from 1991 through 2001. RESULTS: Fourteen patients underwent 15
      procedures. Six patients were males and 8 were females. The diagnosis was Crohn's
      disease in 10 patients and diverticulitis in 4. In 10 cases, the operation was
      the primary procedure, but 5 procedures were for recurrences. Two patients with
      diverticulitis and 3 with Crohn's disease had only the fistulae divided with the
      application of an Endo-GIA stapier across the fistulae (stapled fistulectomy). No
      bowel resections were carried out in these 5 patients. Four cases had to be
      converted due to bleeding (23%). The only postoperative complication was a single
      case of wound infection after conversion. CONCLUSION: The presence of a fistula
      isn't necessarily an indication for conversion. If it is possible to dissect the
      loops free, we believe that a stapled fistulectomy is effective with a low
      incidence of fistula recurrence, especially in Crohn's disease.

PMID- 15554281
TI  - Feasibility and safety of laparoscopic management of hydatid disease of the
      liver.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic treatment of hydatid disease of the liver
      produces encouraging results, though its feasibility and safety have been
      questioned. We evaluated the feasibility and safety of laparoscopic management of
      hydatid disease of the liver. METHODS: Consecutive patients with this disease
      reporting to our department from August 1998 to January 2002 were offered
      laparoscopic management. Our protocol included preoperative albendazole for 4
      weeks, laparoscopic cyst evacuation after its sterilization, and deroofing and
      suction drainage of the cavity, addition of omentoplasty if required, and a
      follow-up exceeding 6 months. RESULTS: Eighteen patients (M11:F7) with 22 liver
      hydatid cysts underwent laparoscopic surgery. The mean cyst size was 7.4 cm
      (range, 5.6 cm to 16.6 cm). Two patients needed conversion to an open operation.
      Spillage of cyst contents occurred in 5 patients. True recurrence of hydatid
      disease occurred in the original site in 2 patients (11%), and false recurrence
      was seen in 2 patients (11%), all within 6 months. CONCLUSION: With proper
      patient selection, laparoscopic management of hydatid cysts of the liver is a
      feasible option with low rates of conversion. Both true and false recurrences are
      common with conservative laparoscopic options, and undetected ectocysts may be
      the cause of true cyst recurrence.

PMID- 15554282
TI  - Open port placement of the first laparoscopic port: a safe technique.
AB  - BACKGROUND: Blind insertion of the Veress needle and of the first trocar is a
      significant cause of complications in laparoscopic surgery. Despite this risk,
      the closed technique is still more popular than the open one. Our aim is to
      report the results of our experience with the routine use of the modified open
      technique in laparoscopic surgery and to describe the technical details of the
      creation of pnuemoperitoneum by the open technique that we used. METHODS: A
      prospective study was conducted in the department of surgery at Maulana Azad
      Medical College and associated Lok Nayak Hospital, New Delhi. A modified method
      of open laparoscopy was performed on 755 consecutive patients requiring
      laparoscopy or laparoscopic surgery over a 5-year period from August 1998 to
      February 2003 in 1 surgical unit. RESULTS: The mean time taken was 4 minutes
      (range, 2 to 10). No intraoperative complications occurred during trocar
      insertion. Forty-nine (6.49%) patients had minor umbilical sepsis, 22 (2.91%) had
      periumbilical hematoma, but none had umbilical hernia during 3 months of follow
      up after surgery. CONCLUSION: Based on our own experience, we recommend open
      laparoscopy as a safe and easy approach for routine laparoscopic interventions.

PMID- 15554284
TI  - Esophageal carcinoma following bariatric procedures.
AB  - BACKGROUND: The long-term success of bariatric operations for weight reduction
      has been well documented, but their potential effects on the risk of esophageal
      cancer have not been evaluated. METHODS: We performed operations on 3 patients
      for esophageal cancer following bariatric operations: 2 had Roux-en-Y gastric
      bypass, and 1 underwent vertical banded gastroplasty. All of these patients had
      adenocarcinoma at the gastroesophageal junction; 1 involved the entire
      intrathoracic esophagus. RESULTS: The intervals between the weight-loss
      operations and cancer diagnoses were 21, 16, and 14 years. All 3 patients had
      symptoms of reflux for many years before dysphagia developed and cancer was
      diagnosed. We performed a limited esophagogastrectomy, a classic Ivor-Lewis
      procedure, and a total esophagectomy with jejunal free-tissue transfer from
      stomach to cervical esophagus. Two patients had positive lymph nodes. One patient
      is alive at 6 years; 2 died at 13 and 15 months after undergoing operation for
      recurrent cancer. CONCLUSION: The effect of bariatric operations on
      gastroesophageal reflux is not known, although gastric bypass has been advocated
      as the "ultimate antireflux procedure." The presence of esophageal cancer in
      these 3 patients years after the weight loss operation is worrisome. We believe
      that patients who develop new symptoms should have endoscopic evaluation and that
      epidemiologic studies on the incidence of esophageal cancer occurring years after
      bariatric operation should be performed.

PMID- 15554283
TI  - Evaluation of operative imaging techniques in surgical education.
AB  - BACKGROUND: Certain open surgical procedures are difficult to observe, and poor
      visualization of the surgical field results in a compromised teaching environment
      for residents and medical students. In an attempt to improve the visualization of
      the open surgical field, we performed an open surgical procedure while viewing it
      via a laparoscope mounted to the side of the operating room table with an alpha
      port. These images were then compared in a blinded fashion with images from a
      boom-mounted camera positioned above the surgical field and a head-mounted camera
      positioned on the operating surgeon. METHODS: Participants viewed all 3 images
      from a remote location in a blinded, random fashion. All participants then
      completed a Likert questionnaire evaluating each image. RESULTS: Fourteen
      participants were in the study. The alpha port/laparoscope image was superior to
      the head-cam image in all 8 categories. The alpha port/laparoscope image was
      superior to the sky-cam image in 4 of 8 categories. All 14 participants felt the
      alpha port/laparoscope image would benefit surgical education CONCLUSIONS: Use of
      a laparoscope mounted via an alpha port to an operating room table provides
      superior images during open surgery. This provides a unique and affordable way to
      teach residents and medical students operative procedures that are otherwise
      difficult to view.

PMID- 15554285
TI  - Laparoscopic treatment of superior mesenteric artery syndrome.
AB  - BACKGROUND: Superior mesenteric artery syndrome is caused by compression of the
      third portion of the duodenum by the superior mesenteric artery. Many disease
      states predispose one to this condition. METHODS: We present a case report of a
      young female patient who presented with gastro-duodenal obstruction from superior
      mesenteric artery syndrome and subsequently underwent surgical treatment with
      minimally invasive techniques. Pathophysiology of SMA syndrome is reviewed.
      RESULTS: The cause of superior mesenteric artery syndrome is variable but always
      results in duodenal obstruction. Surgery is one treatment option that is
      effective and can be performed laparoscopically. CONCLUSION: Laparoscopic
      duodenojejunostomy is an acceptable method of treating superior mesenteric artery
      syndrome.

PMID- 15554286
TI  - Unexpected causes of gynecological pelvic pain.
AB  - During our day-to-day practice, we, as clinicians, occasionally come across
      patients whose symptomatology is atypical. In major teaching hospitals, it is
      usually easy to consult with other specialists to optimize patient management and
      standard of care. Our study patients were treated by the authors between January
      1998 and January 2003. In this article, the authors report on 6 different cases
      of unexpected causes of pelvic pain, all of which were managed in a general
      gynecological unit at a major tertiary referral institution.

PMID- 15554287
TI  - Laparoscopic marsupialization of a giant posttraumatic splenic cyst.
AB  - BACKGROUND AND OBJECTIVE: Nonparasitic cysts are rare clinical lesions of the
      spleen. Causes include congenital malformations and trauma. Historically,
      management has entailed partial or total splenectomy using an open approach.
      Recently, laparoscopic approaches have been developed. In this report, we
      describe laparoscopic marsupialization of a giant splenic cyst (diameter > 15
      cm). METHODS: A 25-year-old African-American man presented with a 9-month history
      of early satiety, constipation, and left upper quadrant pain. Additionally, he
      reported blunt trauma to the abdomen 2 years earlier. Physical examination
      revealed a large, fixed, nontender left upper quadrant mass. Computed tomography
      scan confirmed a simple cyst within the spleen, measuring 20 x 25 cm.
      Echinococcus and Entamoeba histolytica serologies were negative. Laparoscopic
      exploration was performed. Four liters of brown fluid were aspirated and
      intraoperative cytology confirmed a nonparasitic cyst. The cyst wall was excised
      and the cavity was packed with omentum. RESULTS: The patient's recovery was
      uneventful, and he was discharged to home tolerating a regular diet on
      postoperative day 3. At 6-month follow-up, the patient was asymptomatic and
      showed no evidence of recurrence. CONCLUSION: Nonparasitic splenic cysts are rare
      lesions. Laparoscopic marsupialization is safe and effective for giant
      nonparasitic splenic cysts and should be considered the treatment of choice.

PMID- 15554288
TI  - Laparoscopic distal pancreatectomy for lymphoepithelial cyst of the pancreas.
AB  - Lymphoepithelial cysts are rare pancreatic lesions. This case report describes
      the first excision of such a lesion by laparoscopic distal pancreatectomy which
      is a recognized procedure for treatment of cystic pancreatic neoplasms. Our
      patient underwent complete excision of the lesion and has enjoyed complete
      resolution of his symptoms. Laparoscopic distal pancreatectomy may be a suitable
      choice for first-line therapy for such lesions.

PMID- 15554289
TI  - Lumbar incisional hernias: diagnostic and management dilemma.
AB  - INTRODUCTION: Lumbar hernias occur infrequently and can be congenital, primary
      (inferior or Petit type, and superior or Grynfeltt type), posttraumatic, or
      incisional. They are bounded by the 12th rib, the iliac crest, the erector
      spinae, and the external oblique muscle. Most postoperative incisional hernias
      occur in nephrectomy or aortic aneurysm repair incisions. CASE REPORT: We present
      2 patients who had undergone flank incisions and subsequently developed
      significant bulging of that area. The first patient had an atrophy of the
      abdominal wall musculature while the other had a large lumbar incisional hernia
      that was repaired laparoscopically. DISCUSSION: Lumbar incisional hernias are
      often diffuse with fascial defects that are usually hard to appreciate. Computed
      tomography scan is the diagnostic modality of choice and allows differentiating
      them from abdominal wall musculature denervation atrophy complicating flank
      incisions. Repairing these hernias is difficult due to the surrounding
      structures. Principles of laparoscopic repair include lateral decubitus
      positioning with table flexed, adhesiolysis, and reduction of hernia contents,
      securing ePTFE mesh with spiral tacks and transfascial sutures to an intercostal
      space superiorly, iliac crest periosteum inferiorly, and rectus muscle
      anteriorly. Posteriorly, the mesh is secured to psoas major fascia with
      intracorporeal sutures to avoid nerve injury. CONCLUSION: Lumbar incisional
      hernia must be differentiated from muscle atrophy with no fascial defect. The
      laparoscopic approach provides an attractive option for this often challenging
      problem.

PMID- 15554290
TI  - Laparoscopic Roux-en-"W" gastric bypass.
AB  - OBJECTIVES: Roux-en-Y gastric bypass is the gold standard for treating morbid
      obesity in this country. The totally laparoscopic performance of this procedure,
      although quite demanding and technically difficult, has revolutionized it; and
      the demand for it has skyrocketed. We describe 2 cases where it became necessary
      to convert the Y into a "W" while performing the procedure. METHODS: A
      laparoscopic Roux-en-Y gastric bypass was attempted on 2 patients, 1 male and 1
      female, both with body mass indexes greater than 40. During creation of the side
      to side jejunojejunostomy, ie, the Y, it became obvious that stenosis or
      obstruction would result. This area was partially resected and an additional side
      to side anastomosis was formed, creating a "W." RESULTS: The operative time was
      205 minutes and 180 minutes, respectively, which compared favorably with the
      average operative time of 151 minutes in that quartile of patients (patients #101
      #150). Both patients had normal upper gastrointestinal and small bowel contrast x
      rays the day following surgery and were started on clear liquids. They were
      discharged later that day. Weight loss of 119 lb at 8 months and 80 lb at 6
      months was documented, respectively, with no gastrointestinal sequelae.
      CONCLUSION: If problems are encountered when creating the Y of a laparoscopic
      Roux-en-Y gastric bypass, a laparoscopic Roux-en-W may be performed. It appears
      safe, technically feasible, and with a postoperative course not unlike that of
      the standard approach.

PMID- 15554291
TI  - J. Barry McKernan, MD, PhD--a profile.

PMID- 15554292
TI  - [Phylogenetic analysis of facultative methylotrophic bacteria of the genus
      Methylobacterium].
AB  - Phylogenetic analysis of Methylobacterium genus species using analysis of
      nucleotide sequence of 16S rRNA genes has shown that Methylobacterium zatmanii
      and M. rhodesianum possess high-level similarity with M. extorquens (99.4-98.8%),
      and M. fujisawaense and M. radiotolerans--with M. mesophilicum (98.9-97.8%).
      These species are also similar as to their phenotypical properties and their
      total DNAs have also close similarity. Thus, the right of M. zatmanii, M.
      rhodesianum, M. fujisawaense and M. radiotolerans species for existence needs
      confirmation. Some phenotypical properties which were assummed as a basis for
      formation of certain species of the genus Methylobacterium (radioresistance,
      e.g.) cannot serve as the differentiating characteristic of this genus species.
      High resistance to gamma- and UV-radiation is a specific sign of representatives
      of Methylobacterium genus.

PMID- 15554293
TI  - [Study of the topology of the active center of glycosidases of Aspergillus
      niger].
AB  - Activity of alpha-N-acetylgalactosaminidase and alpha-galactosidase isolated from
      the culture medium of micromycete Aspergillus niger v. Tiegh F-16694 has been
      studied as affected by anions, cations and specific chemical reagents (n
      chlormercurybenzoate, L-cysteine, dithiotreitol, beta-mercaptoethanol, EDTA, o
      phenanthroline, sodium azide, hydrogen peroxide). It has been established that
      silver ions noncompetitively inhibit alpha-galactosidase at pH 5.2, the
      inhibition constant (Ki) being 2.5 x 10(-4) M. Galactose in concentration of 1-5
      mM does not protect the enzyme from the negative action of silver ions, but this
      inhibitory effect is almost completely removed by the corresponding
      concentrations of L-cysteine. The same noncompetitive character was inherent in
      the inhibition of alpha-galactosidase reaction by mercury ions and n
      chlormercurybenzoat (Ki is 4.5 x 10(-6) and 1.8 x 10(-4), respectively). The
      importance of sulphydryl groups for the support of active comformation of alpha
      galactosidase molecule was established on the basis of inhibition and kinetic
      analysis. It has been shown that the enzyme molecule does not contain the groups
      which include metal atoms.

PMID- 15554294
TI  - [Convertible energy sources in Neisseria gonorrhoeae].
AB  - Availability of two major sources of convertible energy in gonococci--the
      intracellular pool of ATP and electrochemical potential of hydrogen ions--has
      been established. ATP synthesis occurs when inducing membrane potential by
      creation of K+ gradient with presence of valinomycin and when inducing the proton
      gradient. Transmembrane difference of electric potentials has been determined
      which changes within 103-145 mV under the increase of pH from 5.0 to 8.0, and
      concentration gradient of protons decreases from 80 to 47 mV. The proton-motive
      force value remains unchanged (183-192 mV) in the range of pH 5.0-8.0.

PMID- 15554295
TI  - [Plasmid spectra and phagotypes of Escherichia coli strains isolated from
      patients with large intestine tumours].
AB  - The work deals with connection between plasmid spectra and phagotypes of
      Escherichia coli strains isolated from patients with tumours in large intestine.
      It has been established that 70 % of this bacterium isolates from the normal
      tissue, intestine lumen and tumours are characterized by multiple content of
      plasmids. Sometimes large endogenic plasmids are accompanied by the closed ring
      DNA with discrete sizes: 3.2; 3.8 and 4.0 kb. Other extrachromosomal factors have
      the size of 63-119 kb and are divided into 5 discrete classes. Plasmid DNA which
      size is 69 and 119 kb occur rarely and are characteristic of only E. coli
      isolated from the tumour tissue. Cells of three isolates found in the tissues and
      intestine lumen contain a plasmid complex which consists of three different
      extrachromosomal DNA of 63, 82 and 102 kb. The complex availability correlates as
      a rule with multiple strain resistance to ampicillin, canamycin, and
      tetracycline. Variability of plasmids of clinical E. coli isolates is completed
      regularly by various phagotypes established by means of virulent bacteriophages
      T2, T4, T7, FE44, TuIb, Ox2 and MS2. In most cases one could trace interrelation
      between the plasmid spectrum and phagotype; the same phagotype includes the
      strains with the same set of plasmids. The work results create preconditions for
      the detailed study of the role of microbe factor in development and inhibition of
      tumours.

PMID- 15554296
TI  - [Comparative study of the monosaccharide glycocalyx composition of Bacillus-
      Lactobacillus--Streptococcus bacteria group by biochemical methods and electron
      microscopy].
AB  - Results of comparison of the data on monosaccharide composition of glycocalix in
      group Bacillus--Lactobacillus--Streptococcus bacteria using biochemical and
      electronmicroscopic methods prove that the composition and quantity of
      monosaccharides varied depending on the genus and peculiarities of microorganisms
      strains (biological activity in respect of people and warm-blooded animals). At
      the same time, representatives of this group of microorganisms in the glycocalix
      had common monosaccharides: glucosamine, sialic acids, galactosamine, galactose,
      glucose, mannose, fucose, that is the phenotypical display of genetic relations.

PMID- 15554297
TI  - [Protective action of electromagnetic radiation (40.68 MHz) on Saccharomyces
      cerevisiae UCM Y-517].
AB  - Electromagnetic radiation (EMR) (40.68 MHz, 15 and 30 W) has been studied for its
      effect on survivability of cells of Saccharomyces cerevisiae UCM Y-517 under the
      extremal influence of the environment factors (pH, freezing-thawing, nistatin
      (1.0 microg/ml)). It is shown that even short-term irradiation of the yeast
      suspension (during 5 min) takes protective effect under the conditions of stress
      factors, displayed in the increase of the number of live intact cells. It was
      established by cytochemical methods that 50-70 % of cells were characterized as
      damaged and dead in the control samples after yeast exposition under the stress
      conditions. Such an effect was not observed in the samples of preliminary
      irradiated cells. The pool of extracellular nucleotides was shown to decrease as
      a result of the yeast cells irradiation; one could also observe the decrease of
      these cells ability to acidity the culture medium. The increase of activity of
      intracellular enzymes of dehydrogenase complex was noted as well. Stability of
      electrostatic characteristics of the cell surface (zeta-potential) and catalase
      activity under the effect of EMR of radio-frequency range has been demonstrated.
      The found effect of protective action of EMR of the above frequency is of
      nonspecific character, which allows its mechanism universality to be supposed.

PMID- 15554298
TI  - [Mutagenic action of synthetic fungicides and drugs of biological origin on
      microorganisms].
AB  - Gene-toxical effect of biological and synthetical fungicides on auxotrophic test
      cultures of Salmonella typhimuriun TA 100 and TA 98, and Escherichia coli WP2 has
      been studied. Biological drugs on the basis of hytosan (mycosan and mycosan-new)
      act as weak mutagens. Synthetical fungicides on the basis of benomil and tiram,
      on the contrary, cause higher frequency of mutation. The exceeding of the
      recommended doses of these drugs significantly increases gene-toxical loading.
      This evidences for a necessity to revise agrotechnologies in the direction of
      decrease of the existing standard.

PMID- 15554299
TI  - [Antibiotic and phytotoxic properties of some Aspergillus parvulus Smith
      strains].
AB  - Antibiotic activity screening of 15 species of Aspergillus parvulus were made
      relative to different test-organisms (gram positive, gram negative,
      phytopathogenic bacteria and yeasts) and phytotoxic activity screening relative
      to different algae. The researched strains 3387, 340, 3142, 1813 of A. parvulus
      had a wide spectrum of antibiotic activity and high phytotoxic activity. The rest
      of species had different degrees of antibiotic and phytotoxic activity. For
      further investigation the evaporated cultural filtrate of A. parvulus 3142 was
      separated by the method of column chromatography into fractions with different
      properties. Minimum suppressing concentration (which equals 2 mg/ml for most
      active fraction) was determined for the most active one, and a system of solvents
      was chosen as a results of Schevchic assembly chromatography for the extraction
      of active substance (n-buthanol saturated water).

PMID- 15554300
TI  - [Microflora of damaged ferroconcrete structures under the conditions of
      inhibitory protection].
AB  - Thionic, sulphate-reducing, denitrifying and ammonifying bacteria widely
      distributed in the sewer system on various structure elements have been isolated
      from damaged ferroconcrete samples. Effect of protective materials on microbe
      induced corrosion of metal famework of concrete samples has been studied.
      Selective effect of corrosion inhibitors and coatings on the growth of corrosion
      active bacteria of sulphur and nitrogen cycle has been revealed. It is shown that
      acid medium formed by thionic bacteria is more aggressive than ammonium
      hydrosulphide one formed by denitrifying and sulphate-reducing bacteria. It has
      been established that the corrosion inhibitor--pyrquin, organosilicon coating CO
      FMI and epoxyorganosilicon coating 4sk are most effective materials as to the
      action of thionic bacteria--dangerous agents of ferroconcrete aerobic corrosion.

PMID- 15554301
TI  - [Extraction of a broad range of metals from sewage in the city of Kyiv by mixed
      microbe communities].
AB  - Accumulation of a wide range of metals by the "mixed microbe communities" (MMC)
      from Kyiv sewage treated in the air tank has been studied. MMC is a mixture of
      one or more synthrophical associations, such as microorganisms of fermented
      metantank deposit and cow manure. The exposure being 48 h and weight ratio of the
      phases MMC : sewage being 1:50, MMC lower the concentration of Ca, Fe, Zn, Cc, Au
      in sewage by 1 order; Cr, Mn, Co, Ag, Cd, Ba, Sm, Hf, Th--by 2 orders; Sc, Sb, La
      -by 3 orders. MMC may be used efficiently for deep tertiary treatment of sewage
      for toxical heavy metals, for extraction of rare-earth and non-ferrous metals
      from superdiluted solutions and industrial sewage.

PMID- 15554302
TI  - [Phytopathogenic bacteria in Agaricus bisporus culture].
AB  - Literature sources have been surveyed concerning the two-spore white button
      mushroom (Agaricus bisporus) affected by phytopathogenic bacteria. Yield losses
      and decrease of fruit body quality caused by bacterial spots and rot under the
      conditions of industrial cultivation have been estimated. It has been established
      that the button mushroom affection at the second fruiting break can reach 55%
      that causes the yield shortage of more than 5 kg from 1 m2 and financial losses
      of 1000 Euro for each growing cycle. The bacteria development intensity was found
      to depend on growing by shelves. The most favourable growing conditions were
      observed on the lower shelf; the number of affected mushrooms was 1145-1526
      mushrooms 1 m2 or 95.4% that resulted in the yield losses of 9.5 kg/m2. The loss
      of mushrooms from bacterial rot reached 1.5 kg/m2. The degree of affection of
      fruit bodies was estimated by the developed scale. According to the scale 22.7%
      of mushrooms are fit for realization in fresh or canned form (the infection
      degree 5-10%).

PMID- 15554303
TI  - [Influence of staphylococcal metabolites on adhesive reactions in the system
      "Candida albicans-buccal epitheliocytes"].
AB  - The influence of S. aureus and S. epidermitidis metabolites on the adhesive
      reactions in the system "C. albicans-buccal epitheliocytes" was studied. The
      study revealed that the treatment of C. albicans with S. aureus supernatants
      inhibited the adhesion of C. albicans to epitheliocytes, the degree of the
      inhibiting action of S. aureus supernatants in the system depending on their
      strain specificity. S. epidermitidis supernatants produced no adhesive effect.
      The irreversible decrease of the adhesive activity of C. albicans under the
      action of bacterial metabolites was, seemingly, the consequence of transformation
      of the receptor apparatus of C. albicans. At the same time S. aureus supernatants
      produced no essential influence on the adhesive potential and viability of buccal
      epitheliocytes.

PMID- 15554304
TI  - [Etiology of the epidemic outbreak of community-acquired pneumonia in children in
      St. Petersburg].
AB  - In September-December 1998 the epidemic rise of outhospital pneumonia (EP) among
      children was observed in St. Petersburg, which led to a twofold increase in
      morbidity rate this year. The study of the etiology of EP during the period of
      1998-2001 confirmed the prime role of Streptococcus pneumoniae (74.5%) and, for
      the first time in Russia, revealed the epidemic outbreak of acute chlamydiosis
      (Chlamydia pneumoniae), diagnosed in 67.3% of children, the maximum occurrence
      (87.5%) in 1998 with only 19% of the patients having the disease in the form of
      monoinfection. The prevalence of S. pneumoniae and C. pneumoniae in the etiology
      of EP and more severe course of mixed infection suggested that these infective
      agents played a leading role in the epidemic outbreak of acute respiratory
      infections in St. Petersburg.

PMID- 15554305
TI  - [Role of lectin (hlyA) in the hemolytic and hemagglutinating activity of Vibrio
      cholerae].
AB  - Data on the nature of the substance which determines the structural gene hlyA in
      V. cholerae are presented. Computer analysis and experimental data on hemolysin
      preparations and V. cholerae strains testify that gene hlyA determines the
      synthesis of ricin-like galactose-specific lectin. Its lectin domain takes part
      in the lysis of sheep (but not rabbit!) red blood cells, as well as in the
      hemagglutinating capacity of non-toxigenic and toxigenic V. cholerae 569 B.

PMID- 15554306
TI  - [Salmonella typhimurium population in water environment under the influence of
      temperature].
AB  - The strategy of the adaptation of S. typhimurium population to water environment
      under the influence of temperature factor was studied by scanning electron
      microscopy. Salmonellae were found to adhere to the surface of the Daphnia chitin
      covering. The study revealed that S. typhimurium population existed in water in
      the form of covered microcolonies as well as in the form of spheroplast-type
      cells and small cells in the L-form, joined with bands. The viability of
      salmonellae in water environment was studied without interaction and following
      interaction with Daphnia.

PMID- 15554307
TI  - [Occurrence of markers, distribution of genotypes and risk factors for viral
      hepatitis C among some groups of the population in the Novosibirsk region].
AB  - The occurrence of markers, genotypic variability of isolates and risk factors for
      viral hepatitis C (HCV) were studied in 4 groups of residents of the Novosibirsk
      region (altogether 2,000 persons). Anti-HCV IgG were detected within the range
      from 4.6% among medical personnel to 48% among the patients of the drug-abuse
      clinic. The detection rate of HCV RNA in seropositive samples varied from 79.3%
      to 86.3%. The determination of genotype was carried out for 388 isolates: 1b-
      50.3%, 2a--4.4%, 2c--0.3%, 3a--44.8%. The highest risk indices with respect to
      HCV among the residents of the region were linked with the drug use (OR=77.5;
      p<0.05) as well as with risky behavior and low social status. The elevated
      numbers of seropositive persons were detected among unemployed (OR=16.3), alcohol
      abusers (OR=3.9), persons having more than 4 sex partners in their lifetime
      (OR=4.3) and persons having homosexual contacts (OR=6.6). In some groups blood
      transfusions also played a definite role in the transmission of HCV. In the
      analysis, carried out separately for two different genotypes the intravenous use
      of drugs was perceptibly stronger linked with VHC of genotype 3 (OR=85.5) in
      comparison with HCV of genotype 1 (OR=49.3) and genotype 2 (OR=41.1). Genotype 1
      prevailed in the older age group and genotype 3, among young people.

PMID- 15554308
TI  - [Epidemiological aspects of cytomegalovirus infection in babies aged under one].
AB  - Sreening data obtained on babies aged under one and selected by random (1,910
      children) or target (2,658 children) choice for cytomegalovirus (CMV) infection
      during the period of 10 years (1992-2001) were compared with mortality rate. The
      methods used were enzyme immunoassay, immunofluorescence and polymerase chain
      reaction. The babies were divided as follows: newborn infants (group I), babies
      aged 1-3 months (group II), 4-6 months (group III) and 7-12 months (group IV).
      Specific clinical features of CMV infection in newborn infants were studied on 69
      cases (37--with CMV monoinfection and 32--with mixed infection). The serological
      screening revealed a 2.1-fold growth of the infection rate among randomly
      selected newborn infants during the 10 year period. Positive correlation between
      the infection rate among children of this age group and the neonatal mortality
      rate was established. High risk factors of CMV infection were revealed as well as
      increased infection rate and frequency of clinical cases with the prevailing
      neurological pathology in group III. Early diagnosis, the exclusion of mixed
      infections and early adequate therapy were shown to play a decisive role in the
      outcome of the disease. The algorithm of epidemiological surveillance and the
      regional program of prophylaxis were worked out.

PMID- 15554309
TI  - [Characterization of the foci of meningococcal infection in closed groups of
      males].
AB  - A total of 257 foci of meningococcal infection in groups of servicemen were
      selectively examined in 1982-2002. From these groups 353 patients with
      generalized forms of the disease underwent hospitalization. Most of the foci had
      a single infection, the proportion of foci with 10-40 patients was 82.6%. The
      meningococcal infection rate among humans in the foci was 25-37%, group A
      meningococci playing the leading role. In the structure of meningococcal
      infection generalized forms of infection constituted 16%, localized forms
      constituted 25% and inapparent forms (carriers)--59%. The formation of the
      morbidity structure was influenced by the type of the focus (with a single or
      multiple infection) and the character of morbidity for many years (during
      epidemic or at the period between epidemics). No absolute dependence of the level
      of meningococcal carrier state in the groups of servicemen on the appearance of
      the generalized forms of meningococcal infection was noted. Thus, both during
      epidemic and at the period between epidemics the population of meningococci,
      heterogeneous in its serological structure and differing in its clinical and
      epidemiological importance, constantly circulated with the leading role played by
      group A meningococci.

PMID- 15554310
TI  - [Spread of salmonellosis in Moscow and the ways of its prophylaxis].
AB  - The article deals with the results of the epidemiological analysis of the spread
      of salmonellosis in Moscow. During the last 15 years the proportion of Salmonella
      enteritidis was about 80% and more. After salmonellosis morbidity decreased to
      19.9 per 100,000 of the population (the minimum level) in 1985 its sharp rise was
      noted. Morbidity rate increased from 31.7 in 1987 to 55.1 per 100,000 in 1988,
      then to 93.9 per 100,000 of the population in 1989 (the maximum level). In the
      subsequent years up to 1996 a decrease in morbidity rate was observed, but in
      1997-2002 morbidity rate stabilized within 29.8-35.7 per 100,000 of the
      population without a perceptible tendency towards decrease. The sharp increase of
      the etiological role of S. enteritidis which led to a wide spread of Salmonella
      infections was caused by the "chicken-egg" factor of their transmission. High
      morbidity rate among children and adults, registered all the year round, is the
      consequence of the constant epidemic activity of this factor.

PMID- 15554311
TI  - [Molecular genotyping of Mycobacterium tuberculosis strains isolated from
      patients in the Samara region by the restriction DNA fragment length
      polymorphism].
AB  - The typing of 106 M. tuberculosis (MBT) strains isolated from patients in the
      Samara region by the restriction DNA fragment length polymorphism (RFLP) IS6110
      revealed that most of the strains (71.7%) belonged to the W family, 5 MBT strains
      (4.7%) belonged to the AI family, one culture was the mixture of two strains, AI
      and W. In addition, 24 MBT strains (22.6%) classified with other genotypes were
      detected. The analysis of the sensitivity of the MBT strains to rifampicin and
      isoniazid, with the method of absolute concentrations and by point mutations,
      demonstrated that 29 MBT strains (27.3%) were sensitive to rifampicin and
      isoniazid and 56 MBT strains (52.9%) were resistant to rifampicin and isoniazid
      simultaneously. Among the MBT strains of different RFLP families, strains both
      sensitive and resistant to these two preparations could be detected, but strains
      with multiple drug resistance prevailed in the W family (61.8%).

PMID- 15554313
TI  - [Computerized analysis of inverted repeats in Mycobacterium tuberculosis genome].
AB  - Thermodynamic stable inverted repeats, capable of stabilizing nuclease-influenced
      mRNA, have been determined for M. tuberculosis slowly growing isolates H37Rv and
      CDC1551 with the completely sequenced genome. The genome of laboratory strain
      H37Rv may contain 50 pin structures formed by inverted repeats, whose stem varies
      in length from 11 to 28 nucleotide pairs (n.p.), the loop size being equal to 4-5
      nucleotides and free energy deltaG=-15.2 to -56.2 kcal/mol. The genome of strain
      CDC1551 (clinical isolate) having a high level of virulence contains 47 pins.
      Each of the two isolates contains 8 long inverted repeats with a length of 48-62
      nucleotides and free energy deltaG=-38.9 to -56.2 kcal/mol; of these, 6 pins are
      completely similar. At the same time in the genome of strain CDC1551, in contrast
      to that of strain H37Rv, a highly stable pin 58 nucleotides long is localized at
      5'-end. The localization of the highly stable pin with deltaG=-53.9 kcal/mol in
      the area of 5'-end of isolate CDC1551 may lead to a different degree of
      stabilization of RNA-transcripts in M. tuberculosis CDC1551 in comparison with
      isolate H37Rv. This may, in its turn, serve as one of the reasons of differences
      in the virulence of strains. The possibility of the formation of pins with stems
      of 11 n.p. and longer has been visually cofirmed with the use of atomic power
      microscopy. The possibility of the participation of the secondary structures
      formed by pins in the protection of mRNA of slowly growing pathogenic M.
      tuberculosis from the degrading activity of RNases is discussed.

PMID- 15554312
TI  - [Genetic identification of rickettsiae of the tick-borne spotted fever group,
      isolated in the foci of tick-borne rickettsiosis].
AB  - A total of 25 rickettsial cultures of the tick-borne spotted fever (TBSF) group
      from the collection of the Research Institute of Infections in Omsk, isolated
      from different sources in the territory of the Russian Federation (from the Urals
      to the Far East) during the period of 1954-2001) were studied by the methods of
      genetic analysis. The fragments of the gene coding the outer-membrane protein of
      190 kD (ompA) and synthetase citrate (gltA) of the rickettsiae under the study
      were sequenced. 23 isolates were identified as R. sibirica, among them 3 isolates
      obtained from patients, 16 isolates obtained from Dermacentor ticks, 2 isolates
      from Haemaphysalis concinna and 2--from Ixodes persulcatus. The strain Primorye
      32/84, isolated from D. silvarum ticks in the Far East and earlier identified as
      S. sibirica by the results of the PCR-RFLP analysis proved to be a genovariant
      Rickettsia spBJ-90, i.e. close to this species. Strain Karpunino 19/69, isolated
      in the Kurgan region, was identified as R. slovaca. The results obtained extended
      our notions of the spectrum of rickettsiae group TBSF in Russia as well as their
      vectors.

PMID- 15554314
TI  - [New recombinant variant of human immunodeficiency virus of type 1, subtype
      envB/envA, isolated in Novosibirsk].
AB  - The nucleotide sequence of the variant of human immunodeficiency virus of type 1
      (HIV-1), mostly widespread on the territory of the Novosibirsk region, was
      determined. The analysis of the nucleotide sequence confirmed that this variant
      belonged to HIV-1 of subtype A. The HIV-1 recombinant variant of subtype
      envB/envA with the recombination area within the second conservative region C2 of
      gene env, so far unknown, was detected and characterized. In HIV-1 the area at
      the beginning of gene env (5'-env) was found to belong to subtype B and the
      sequence at the end of gene env (3'-env), to subtype A. The analysis of the amino
      acid sequence of the third variable region of gene env demonstrated that the
      viruses under study belonged to macrophagotropic "slow/low" variants,
      characterized by low replication speed. The analysis of nucleotide sequences of
      the isolated variants of HIV-1 revealed their close genetic relationship with HIV
      1 isolates circulating on the territory of Ukraine.

PMID- 15554315
TI  - [Evaluation of the reactogenicity and immunogenic potency of combined vaccine
      "Bubo-Kok" in the immunization of children against diphtheria, tetanus, pertussis
      and viral hepatitis B].
AB  - Combined vaccine "Bubo-Kok" is characterized by safety and high immunological
      activity. The number of postvaccinal reactions in children aged 1 and 2 years,
      immunized with vaccine "Bubo-Kok", was not statistically different from those in
      groups of children immunized with adsorbed DPT vaccine, as well with such vaccine
      in combination with vaccine against hepatitis B. After the completion of the
      primary course of immunization 100% of children had protective antibody titers
      against diphtheria, tetanus and hepatitis B. Antibody titers against pertussis,
      equal to or exceeding protective titers, were found in more than 70% of immunized
      children. The immunogenic potency of vaccine "Bubo-Kok" with respect to all its
      components was not inferior to that of adsorbed DPT vaccine and vaccine against
      hepatitis B, when introduced simultaneously in different areas of the body.
      Vaccine "Bubo-Kok" successfully passed state trials and was recommended for
      registration.

PMID- 15554316
TI  - [Total immunization of children against influenza decreases morbidity in a number
      of diseases among elderly persons during influenza epidemic].
AB  - Immunization of children aged 3-6 years in kindergartens and school children aged
      7-17 years against influenza with inactivated influenza vaccine was carried out
      in two districts of the Moscow region. The comparison of morbidity in influenza
      like diseases among the immunized children with that among nonimmunized children
      in control districts revealed that the effectiveness of immunization was 60.9% in
      kindergartens and 68.8% in schools. The analysis of morbidity in a number of
      diseases among 158,451 elderly persons not immunized against influenza
      demonstrated that, in comparison with the control districts, in those districts
      where mass immunization of children was carried out morbidity in influenza-like
      diseases among elderly persons was 3.4 times lower and, out of other 10 diseases
      under study, morbidity in 8 diseases was 1.5-2.6 times lower. As indicated by the
      data obtained in this study, total anti-influenza immunization of children in
      organized groups not only essentially decreased influenza morbidity among
      children, but also greatly decreased morbidity in influenza and a number of
      diseases, appearing as complications of influenza infection, among nonimmunized
      elderly persons during influenza epidemic.

PMID- 15554317
TI  - [Evaluation of the stability of pertussis vaccine OCO-3 standard].
AB  - The evaluation of the immunogenic activity and residual toxicity of the National
      Standard of pertussis vaccine (OCO-3) was carried out. As shown by observations
      lasting for a period of 25 years, the preparation possesses stable immunogenicity
      and its toxicity remained unchanged, which makes it possible to use OCO-3 for the
      routine control of the pertussis component of commercial lots of adsorbed DPT
      vaccine.

PMID- 15554318
TI  - [Humoral immune response in animals after the oral administration of group C
      meningococcal whole-culture preparation].
AB  - Experimental data giving grounds for the development of a new group C
      meningococcal whole-culture preparation for oral administration are presented.
      The study revealed that the use of the controlled cultivation of group C
      meningococci and a nutrient medium with definite chemical composition in
      combination with the "soft" method of the isolation of the whole-culture
      preparation ensured the preservation of polysaccharide, outer membrane protein
      and lipooligosaccharide in a native state, as well as retaining their full
      antigenic value, in the preparation. The oral immunization with the whole-culture
      preparation stimulated the multiple elevation of the level of hemagglutinating
      and IgG antibodies to these antigens and their prolonged preservation in the
      blood of immunized animals.

PMID- 15554319
TI  - [Specific features of humoral immunity in cryptogenic fibrosing alveolitis
      patients].
AB  - Cryptogenic fibrosing alveolitis (CFA) is a severe autoimmune disease of unclear
      etiology and prognostically unfavorable. The complexity of the diagnostics of
      this disease makes it necessary to search for new methods; for this reason
      immunity in CFA patients must be studied. The study of humoral organ-specific,
      organ-unspecific and antibacterial immunity of CFA patients revealed that the
      latter differed from the members of the groups used for comparison by a higher
      frequency of positive reactions in EIA determinations of IgG antibodies to
      cytokeratin-8 and Moraxella catarrhalis antigens. In addition, only in CFA
      patients a high degree of correlation (r=0.88) between these results was
      established. This made it possible to propose to use these reactions for
      confirming the diagnosis of CFA and suggested the probable role of M. catarrhalis
      in triggering autoimmune reactions characteristic of this disease.

PMID- 15554320
TI  - [Reactivity of Candida albicans in the system of the alternative way of
      complement activation].
AB  - The neutrophil-stimulating activity of C. albicans before and after opsonization
      in the system of the alternative way of complement activation (AWCA) was studied.
      The study revealed that, in comparison with zymosan, C. albicans exhibited a
      considerably lower index of AWCA-dependent opsonic effect in reaction with
      neutrophils. This did not correlate with the capacity of substrates to activate
      the alternative cascade and with the intensity of phagocytosis. The suggestion on
      the involvement of C. albicans thermolabile cell-wall components into the
      negative regulation AWCA-dependent opsonic effect was substantiated.

PMID- 15554321
TI  - [Immune response in experimental animals immunized with Burkholderia pseudomallei
      surface antigens].
AB  - The influence of the chromatographic fractions of B. pseudomallei surface
      antigenic complex (C, C1, D, H) on immune response in white rats and white mice
      was under study. These antigenic complexes were noted to produce perceptible
      stimulating effect on the immune system of white rats, in contrast to that of
      white mice. The immunization of the mice the above-mentioned fractions suppressed
      the phagocytic activity of peritoneal macrophages (PM) and slightly enhanced cell
      mediated immunity. In experiments on white rats, fraction C induced the growth of
      specific antibody titers and stimulated the phagocytic activity of PM, as well as
      the indices of delayed hypersensitivity (DH). Fraction D showed a lower level of
      the induction of the phagocytic activity of PM and was inactive in the
      manifestation of cell-mediated immunity, but induced a high level of humoral
      immunity. Antigenic complexes C1 and H increased the phagocytic activity of PM
      and DH characteristics with a low level of antibody production. The studied
      fractions of the causative agent of melioidosis decreased the content of
      bactericidal cationic proteins (BCP) in rat blood neutrophils, and in mice a
      decreased content of BCP in phagocytes was registered. The fractions increased
      the activity of myeloperoxidase in blood neutrophils in mice and rats. As
      revealed with the use of immunoelectrophoresis, SDS PAAG electrophoresis and
      immunoblotting, the surface antigenic complex contained proteins of 18, 22, 39 kD
      and glycoproteins 42, 55, 90 kD. The latter glycoprotein was found in all the
      fractions under study, having protective properties.

PMID- 15554322
TI  - [Coronavirus infection in immunodeficient patients with hemoblastosis and
      deficient hemopoesis].
AB  - Coronavirus infection (CVI) was studied in 227 patients hospitalized in the
      clinic of the Research Institute of Hematology and Transfusiology in 1993-2003
      with diagnosed acute and chronic leucosis, multiple myelogenic disease and
      aplastic anemia. Their blood sera and secretions of the nasal cavity were
      examined in the indirect hemagglutination (IHA) test with dried standard
      erythrocyte diagnostic preparations. CVI was shown to be activated in three year
      cycles in immunodeficient patients, which occurred, respectively, in 66.1, 56.9,
      47.8 and 51.6% of cases in the above mentioned groups of patients. In 87% of
      cases CVI was associated with other respiratory pathogens, the following being
      prevailed: respiratory syncytial virus (37.9%), parainfluenza virus (32.2%) and
      Mycoplasma pneumoniae (36.8%). CVI was provoked by such factors as the course of
      the main disease and specific treatment, previous respiratory infections of other
      etiology with M. pneumoniae infection playing the leading role (60%). The most
      severe course of CVI was observed in patients with acute leucosis (in 75% of
      cases accompanied by lesions of lower respiratory tracts). The use of the highly
      sensitive IHA test made it possible to determine the potential for both serum and
      local antibodies production in the patients under observation.

PMID- 15554323
TI  - [Quantitative characterization of antagonistic activity of lactobacilli].
AB  - In this work the method of serial dilutions of lactobacilli in two-layer agar was
      used. On the agar surface bacterial or fungal cultures were applied at different
      time intervals. A special quantitative characteristic was introduced. L.
      plantarum strain 8P-A3 was shown to have the maximum antagonistic activity. In
      great amounts L. casei and L. reuteri are capable to suppress the growth of
      bacteria and fungi. All lactobacilli under study produced a pronounced
      bactericidal effect on Pseudomonas, had different influence on the viability of
      Escherichia and staphylococci and exhibited fungistatic and fungicidal action
      only when inoculated at high concentrations.

PMID- 15554325
TI  - [Comparative characterization of laboratory-made selective nutrient media for
      Salmonella accumulation].
AB  - In this work the results of the trial of three selective nutrient media for
      Salmonella accumulation, viz. Leifson's selenite broth produced by the Research
      and Manufacturing Amalgamation (RMA) "Nutrient Media", tetrarathionate broth
      (Muller's medium), laboratory-prepared, and newly developed MA-broth produced by
      the RMA "Nutrient Media", are presented. The results of 6- and 24-hour incubation
      in these selective media was evaluated. As found in this study, the laboratory
      prepared medium was most effective for the accumulation of salmonellae (S.
      paratyphi, S. typhi, S. gallinarum). With respect to the possible concomitant
      microflora (Escherichia coli and shigellae), the inhibiting properties of MA
      broth were superior to those of Leifson's medium, but inferior to those of
      Muller's medium.

PMID- 15554324
TI  - [Postvaccinal antidiphtheria and antitetanus immunity in patients with systemic
      connective tissue diseases].
AB  - The retrospective evaluation of the intensity of postvaccinal immunity at
      different periods after the primary course of immunization against diphtheria and
      tetanus was made. In the sera taken from 130 children with systemic connective
      tissue diseases the content of antibodies to diphtheria and tetanus was
      determined. As revealed in this study, the protective levels of antibodies to
      diphtheria and tetanus toxoids were retained by both sick and healthy children
      for 5 years and longer. Significantly lower titers of antibodies to diphtheria
      and tetanus toxoids were registered in children undergoing therapy with
      glucocorticosteroids and cytostatics at the time of the study.

PMID- 15554326
TI  - [Characterization of bacteria of the genera Mycobacterium, Rhodococcus and
      Nocardia isolated from environmental objects in the Republic of Daghestan].
AB  - The bacteriological study of specimens taken from environmental objects,
      biomaterials from animals and sputa from tuberculosis patients revealed the
      ubiquity of Mycobacterium, Nocardia and rhodococci obtained from different kinds
      of environment in the Republic of Daghestan. In the identification 83.6% out of
      the isolated atypical Mycobacterium cultures were classified with Ranion groups
      II and IV. Among Nocardia, the most widespread organisms were N. asteroides
      (62.7%) and among rhodococci, R. erithropolis (61.9%).

PMID- 15554327
TI  - [Hemolytic activity of Vibrio cholerae eltor and V. cholerae O139 toxigenic and
      nontoxigenic strains].
AB  - A total of 20 ctx- and 16 ctx+ V. cholerae eltor strains, 20 ctx- and 22 ctx+ V.
      cholerae O139 strains were under study. Hemolytic activity was tested in modified
      Greig test with sheep, guinea pig and rabbit red blood cells. The comparative
      study of the hemolytic properties of V. cholerae O1 and O139 under different
      conditions of cultivation demonstrated their capacity of lysing sheep red blood
      cells (SRBC) irrespective of the presence of toxigenic properties. A wider
      spectrum of lytic activity of ctx- strains in Greig test with respect to red
      blood cells of different animals and the capacity of lysing SRBC, most resistant
      to the action of toxin, may be due to a considerably greater content of Hly+
      clones in their population.

PMID- 15554328
TI  - [Identification and differentiation of pathogenic Burkholderia].
AB  - In this review modern methods for the identification and differential diagnostics
      of the causative agents of glanders and melioidosis, recently included into the
      genus Burkholderia, are presented. The known phenotypic signs and genetic markers
      permitting the identification of two pathogenic microorganisms on the definite
      taxonomic level are described.

PMID- 15554329
TI  - [Role of lipopolysaccharide in the action of complement on gram negative
      bacteria].
AB  - In this review a short description of the methods for the activation of the
      complement system and data on the role of different structures of
      lipopolysaccharide of gram negative bacteria in this process are presented.
      Variants of complement-induced bacteriolysis are considered. Special attention is
      given to cholera infection and the role of Vibrio cholerae O139 polysaccharide in
      interaction with the complement.

PMID- 15554330
TI  - Avian influenza, Thailand--update.

PMID- 15554331
TI  - Update: investigation of rabies infections in organ donor and transplant
      recipients--Alabama, Arkansas, Oklahoma, and Texas, 2004.

PMID- 15554332
TI  - Tenth informal consultation on the global polio laboratory network, 6-8 September
      2004.

PMID- 15554333
TI  - Patient safety proves elusive. Five years after publication of the IOM's 'To Err
      is Human,' there's plenty of activity on patient safety, but progress is another
      matter.
AB  - Five years after the Institute of Medicine shook up the industry with its To Err
      is Human report, patient safety is a hot topic, but few hospitals have reached
      the IOM's goal of halving mistakes by 2004. "We've only begun," says Donald
      Berwick, left, president and CEO of the Institute for Healthcare Improvement.

PMID- 15554334
TI  - Good news, bad news. Hospitals' net profit margin up, operating margin down.

PMID- 15554335
TI  - Sky's the limit. Insurance industry reports increased profit margins.

PMID- 15554336
TI  - Bad-debt woes grow at chains.

PMID- 15554337
TI  - Staffing strife. SEIU files nurse-patient ratio complaints in California.

PMID- 15554338
TI  - Too many cooks. FTC, Justice Department call consent decrees ineffective.

PMID- 15554339
TI  - Industry probe. Justice Department subpoenas dialysis providers.

PMID- 15554340
TI  - No gain-sharing in N.J. CMS won't try to revive pay-for-performance plan.

PMID- 15554341
TI  - Calif. docs grab more pie.

PMID- 15554342
TI  - The rules we follow. An updated ethics code for our staff.

PMID- 15554343
TI  - Kickback trial opens for Tenet.

PMID- 15554345
TI  - Evangelism and Antagonism. Integris CEO sees healthcare as near-spiritual
      calling, but woe unto those supporters of specialty hospitals.

PMID- 15554346
TI  - Changes in plasma growth hormone (GH) and secretion patterns of GH and
      luteinizing hormone in buffaloes (Bubalus bubalis) during growth.
AB  - To assess the changes of plasma growth hormone (GH) and secretion patterns of GH
      and luteinizing hormone (LH) during growth in buffaloes, six growing female
      Murrah buffalo calves (mean age 6+/-0.9 months and body weight 66+/-6 kg) were
      selected. Plasma samples were collected twice a week for 52 weeks for GH and LH
      assay. To examine for pulsatile secretion samples were collected at 15 minutes
      interval for 9 hr at weeks 6 and 42 for GH and LH measurements. Plasma
      progesterone was also estimated in twice-a-week samples to assess whether any of
      the buffalo had begun ovarian cyclicity. The body weight of all animals was
      recorded at weekly interval. Plasma GH concentration decreased (P < 0.01) only up
      to week 29 and showed an increasing trend (P < 0.01) thereafter. The ratio of
      plasma GH to body weight declined (P < 0.01) throughout the entire experimental
      period. Plasma GH showed a declining trend only up to when the animals attained
      155 kg body weight and thereafter showed an increasing trend (P < 0.01). Plasma
      GH revealed distinct pulsatile patterns of release, with a mean of 6 and 5 pulses
      in the 6-week and 42-week samples, respectively. The plasma LH concentrations
      around the 42-week time period were significantly higher (P < 0.01) than at the 6
      week time period, and they exhibited pulsatility. No animal reached puberty until
      the end of the experiment. In summary, plasma GH levels have a definite pattern
      of change during growth and patterns of secretion of plasma GH and LH also have a
      relation with body weight in this species of animal.

PMID- 15554347
TI  - Cerebral vasoreactivity in children and adolescents with type 1 diabetes
      mellitus.
AB  - It is well established in clinical and experimental settings that diabetes
      mellitus, especially if long lasting, impairs autoregulation of cerebral blood
      flow (CBF). However, the onset and the course of development of this dysfunction
      remain unknown. We hypothesized that assessment of autoregulatory functions of
      cerebral arteries in children with relatively short duration of type 1 diabetes
      mellitus may provide an insight into the pathophysiology of the development of
      impaired autoregulation of CBF. Such a dysfunction of vasodilation of cerebral
      arteries can be assessed by transcranial Doppler. Therefore, to examine whether
      and when autoregulation of CBF becomes affected by diabetes, we used transcranial
      Doppler and a pCO2 challenge in 17 males between the ages of 12-20 years with
      type 1 diabetes mellitus of 0.2-16 years duration and with varying degrees of
      glucose control. The results were compared with age-matched, healthy, nondiabetic
      controls. The CO2 challenge increased cerebral blood-flow velocities and
      decreased the pulsatility index. These changes were not influenced by the
      presence or duration of diabetes, insulin dose, or degree of diabetic control.

PMID- 15554348
TI  - Effect of androgen ablation on prostatic cell differentiation in dogs.
AB  - This study was conducted to gain further insight into the role of androgen in
      maintaining a balanced prostate gland growth in dogs. Effects of castration on
      prostatic cell were assessed by comparing the expression level of high molecular
      weight cytokeratin (HMW), alpha-actin, and vimentin in intact and castrated dogs.
      Mature dogs were castrated while they were under general anesthesia and were
      killed after 1 month. Mature prostate gland structures from intact dogs are
      characterized by the presence of differentiated columnar secretary epithelial
      cells and progenitor basal cells that are located within acini and ducts embedded
      in a thin fibromuscular tissue. Basal cells were distinguished from secretory
      epithelial cells by HMW cytokeratin immunostaining, which is expressed
      specifically by basal cells but not by epithelial cells. Castration-induced
      secretory epithelial cell death, leave the basal cells intact to form a
      continuous layer lining the atrophied acini. However, the survived basal cells
      lost their capacity to differentiate to secretory epithelial cells. In addition,
      androgen ablation induced remarkable reorganization of the cellular components of
      the fibromuscular compartment. In intact dogs, this compartment of prostate gland
      is composed mainly of differentiated smooth muscles and scattered mesenchymal
      muscles as reflected by the high and low actin and vimentin expressions,
      respectively. Castration for 1 month induced a progressive shift toward
      mesenchymal cells, which appeared to occupy most of the fibromuscular
      compartment. Based on these findings, it appears that androgen acts to maintain a
      steady state of prostate gland by driving the differentiation of prostatic cells
      and by maintaining its fully differentiated state.

PMID- 15554349
TI  - Leptin release is decreased in white adipocytes isolated from progesterone
      treated rats.
AB  - Previously, it has been proposed that progesterone has an inhibitory effect on
      leptin secretion by white adipocytes, because female rats treated with
      progesterone show unchanged plasma leptin concentrations despite heavier fat
      depots. In this study, we show that adipocytes isolated from intact rats release
      the same amount of leptin either in the presence or the absence of progesterone
      in the incubation medium. However, when we isolated white adipocytes from
      progesterone-treated and sham-treated rats and measured their leptin release for
      6 hr, we found that adipocytes isolated from rats treated with progesterone for
      72 hr showed a lower leptin release than those of sham-treated rats. These
      results confirm the proposed inhibitory action of progesterone on leptin
      production.

PMID- 15554350
TI  - The effect of fenofibrate on the levels of high sensitivity C-reactive protein in
      dyslipidemic obese patients.
AB  - It is now well documented that obesity is associated with a chronic low-grade
      inflammatory state. Levels of high-sensitivity C-reactive protein, a marker of
      systemic inflammation and a mediator of atherothrombotic disease, have been shown
      to correlate with cardiovascular disease risk. Our objective was to evaluate the
      effect of fenofibrate on the levels of high-sensitivity C-reactive protein in
      dyslipidemic obese patients. We selected 30 dyslipidemic obese patients (body
      mass index > or = 30 kg/m2) and 20 normolipidemic, nonobese healthy subjects.
      Dyslipidemic obese patients were treated with fenofibrate 200 mg/day for 3
      months. Serum high-sensitivity C-reactive protein and metabolic parameters were
      evaluated at baseline in both groups and after fenofibrate treatment in
      dyslipidemic obese patients. At baseline, significantly higher high-sensitivity C
      reactive protein levels were found in dyslipidemic obese patients than normal
      subjects (0.58+/-0.3 vs 0.14+/-0.1 mg/dL, P < 0.01). Total cholesterol, low
      density lipoprotein cholesterol, and triglyceride decreased significantly (P <
      0.05, P < 0.05, and P < 0.01, respectively), and levels of high-density
      lipoprotein cholesterol significantly increased (P < 0.05) after treatment with
      fenofibrate in the dyslipidemic obese group. Levels of high-sensitivity C
      reactive protein decreased significantly (approximately 74.1%) after fenofibrate
      treatment from a mean of 0.58+/-0.3 mg/dL to 0.15+/-0.2 mg/dL, P < 0.01. Our
      findings suggest that fenofibrate may be used as a first-line therapy for
      improving the plasma lipids profile, as well as the chronic low-grade
      inflammatory state in dyslipidemia and obesity.

PMID- 15554351
TI  - Homocysteine concentrations in subclinical hypothyroidism.
AB  - Hyperhomocysteinemia is considered to be an independent risk factor for
      atherosclerotic heart disease, including coronary artery disease (CAD). It is
      already known that overt hypothyroidism gives rise to a slight
      hyperhomocysteinemia. However, the effects of subclinical hypothyroidism on the
      levels of homocysteine are not known. In this study, we have evaluated
      homocysteine levels and the effect of L-thyroxine treatment in patients with
      subclinical hypothyroidism. For the purpose of the study, we selected 33 women
      patients with the diagnosis of subclinical hypothyroidism but without clinical
      CAD. After a euthyroidism development period of almost four months, a further
      study was done on patients who had been treated with thyroid hormone. The patient
      group was compared with 25 healthy control female subjects who were of similar
      age. In the patient group, homocysteine levels prior to treatment were
      significantly higher than in the control group (P < 0.001). After L-thyroxine
      treatment, homocysteine levels were reduced significantly. In summary, we found
      that homocysteine levels were in the normal range in subclinical hypothyroidism.
      However, when compared with the healthy control group, the difference between
      them was significant. On the other hand, therapy to produce euthyroidism caused a
      significant reduction in homocysteine levels.

PMID- 15554352
TI  - Effects of dihydrotestrone on osteoblast gene expression in osteopenic
      ovariectomized rats.
AB  - Androgens stimulate bone formation, however, the precise mechanism of androgen
      action on osteoblasts remains to be elucidated. In this study, we defined the
      expression profile of osteoblast genes in ovariectomized rats with established
      osteopenia and their response to treatment with dihydrotestosterone (DHT). Twenty
      four, 8-month-old female Sprague-Dawley rats were ovariectomized (ovx) and were
      administered vehicle, 40 mg, 80 mg, or 160 mg/kg body weight DHT at 15-weeks post
      ovariectomy for 14 weeks. Alkaline phosphatase (ALP) messenger ribonucleic acid
      (mRNA) levels were increased at 29-weeks post-ovariectomy compared with
      preoperative rats (P < 0.05). In contrast, osteopontin and osteocalcin mRNA
      levels were unchanged. Treatment of osteopenic ovx rats with DHT for 14 weeks
      suppressed the ovariectomy-induced increase in ALP (P < 0.05) mRNA levels,
      independent of dose. These data suggest that androgens may act to inhibit the
      stimulation of the early stages of osteoblast development that occurs in the
      absence of estrogen and in states of low bone turnover.

PMID- 15554353
TI  - Stimulation of RANKL and inhibition of membrane-type matrix metalloproteinase-1
      expression by parathyroid hormone in normal human osteoblasts.
AB  - Receptor activator of NF-kappaB (RANK) ligand (RANKL), expressed by cells of the
      osteoblast lineage binds to RANK, induces signaling and a gene expression cascade
      that leads to osteoclast differentiation and activation. Recently, osteoblast
      derived membrane-type matrix metalloproteinases-1 (MT1-MMP) have been implicated
      in the process of bone resorption by degrading bone matrix. In the present study,
      we investigated the effects of parathyroid hormone [PTH (1-34)] on RANKL and MT1
      MMP production in cultured normal human osteoblast-like cells (hOB). In reverse
      transcription polymerase chain reaction studies, we observed that PTH (1-34)
      induced RANKL messenger ribonucleic acid (mRNA) expression. Activity assays
      demonstrated that PTH (1-34) simultaneously inhibited MT1-MMP protein expression
      in a dose- and time-dependent manner. The effect of PTH (1-34) on MT1-MMP
      production was parallel to that on RANKL expression, suggesting a tight inverse
      relationship between MT1-MMP and RANKL expression. Our findings indicated that
      the decreased MT1-MMP expression by PTH may be involved in RANKL signaling in
      osteoblasts and activation of osteoclasts.

PMID- 15554354
TI  - Soluble leptin receptor and leptin levels in pregnant women before and after
      delivery.
AB  - Soluble leptin receptor is an extracellular domain of the leptin receptor that
      serves as the main leptin-binding protein and may play a role in the regulation
      of leptin tissue effects. The aim of our study was to assess serum concentrations
      of leptin, soluble leptin receptor, and other hormones involved in the regulation
      of leptin secretion in pregnant women before and after delivery. Serum leptin,
      cortisol, and tumor necrosis factor alpha (TNF-alpha) concentrations in 19
      pregnant women before delivery were significantly higher than in healthy
      nonpregnant women (33.3+/-21.0 vs. 7.9+/-3.5 ng/mL, 1068.9+/-442.2 vs. 546.6+/
      165.3 nmol/L, 4.4+/-1.1 vs. 3.4+/-1.2 ng/mL, respectively). In contrast, no
      differences between these groups were found in soluble leptin receptor levels.
      Delivery significantly decreased serum leptin and cortisol levels and increased
      soluble leptin receptor levels (12.3+/-9.1 ng/mL, 749.6+/-205.3 nmol/L, 23.3+/
      7.9 U/mL, respectively). Soluble leptin receptor levels after delivery became
      higher than in the control group. We conclude that serum leptin and serum soluble
      leptin-receptor levels are significantly affected by pregnancy and delivery. The
      regulation of leptin levels in this group of patients appears to be distinct and
      independent of soluble leptin-receptor levels.

PMID- 15554355
TI  - Comparative assessment of the inhibition of recombinant human CYP19 (aromatase)
      by azoles used in agriculture and as drugs for humans.
AB  - Azoles (imidazoles and triazoles) are used as antifungal agents in agriculture
      and in medicine, and also for antiestrogen therapy, e.g., for breast cancer
      treatment. Antifungal activity is based on inhibition of fungal CYP51 (lanosterol
      14alpha-demethylase), and estrogen biosynthesis reduction is due to azole
      inhibition of CYP19 (aromatase). Inhibition of aromatase by antifungal agents is
      usually an unwanted side effect and may cause endocrine disruption. A
      fluorimetric assay based on human recombinant CYP19 enzyme with
      dibenzylfluorescein as a substrate was used to compare the inhibitory potency of
      22 azole compounds. Dose responses were established and duplicate datasets were
      analyzed with a nonlinear mixed-effects model with cumulative normal distribution
      for the logarithm of concentration. IC50 values (50% inhibitory concentration) of
      13 fungicides used in agriculture ranged more than 700-fold, starting from 0.047
      microM. The potency of seven human drugs spanned more than 7000-fold, starting
      from 0.019 microM. Most potent fungicides included prochloraz, flusilazole, and
      imazalil, and most potent medicinal antifungals were bifonazole, miconazole, and
      clotrimazole. These in vitro data indicate that the top-ranking azoles used as
      antifungal agents or drugs are as potent inhibitors of aromatase as are
      antiestrogen therapeutics used to treat breast cancer. These putative effects of
      azole agents and drugs on steroid biosynthesis and sex hormone balance should be
      considered when used in human subjects and also in wildlife exposed to azole
      fungicides used in agriculture.

PMID- 15554356
TI  - Point of care blood ketone testing of diabetic patients in the emergency
      department.
AB  - The aim of our study was to determine the utility of point-of-care blood ketone
      testing in diabetic patients presenting to the emergency department. In this
      prospective, observational clinical study, patients with known or newly diagnosed
      diabetes mellitus presenting to our tertiary care university emergency department
      with any nontrauma related medical complaint and a high fingerstick glucose (> or
      =200 mg/dL) were eligible for inclusion. Capillary blood beta-hydroxybutyrate
      (beta-HBA), venous blood beta-HBA level, venous blood glucose level, arterial
      blood gas analysis, and urine ketone dipstickstick were measured in each patient
      as primary outcome measures. Of the 479 diabetic patients presenting during the
      study period, a total of 139 diabetic patients with high capillary blood glucose
      level (> or =200 mg/dL) and a positive capillary blood beta-HBA (> or =0.1
      mmol/L) were included in the study. Hyperketonemia (> or =0.42 mmol/L) was found
      in 48 of these patients by Sigma Diagnostics reference testing (diabetic ketosis
      in 35%). The calculated blood pH was less than 7.3 in 18 of these 48 patients
      (ketoacidosis in 31%). Capillary and venous blood beta-hydroxybutyrate levels
      were not statistically different from each other (P = 0.824). There was a
      positive correlation between capillary and venous blood beta-HBA levels (r =
      0.488, P < 0.001). The sensitivity and specificity of urine ketone dipstick
      testing and capillary blood ketone testing in determining diabetic ketoacidosis
      were 66% and 78%, and 72% and 82%; and in determining hyperketonemia (both in
      diabetic ketosis and diabetic ketoacidosis) were 82% and 54%, and 91% and 56%,
      respectively. A rapid, bedside capillary blood ketone test for beta-HBA can
      accurately measure blood concentrations of beta-HBA in diabetic patients in an
      emergency department setting. This device can be used as a reliable diagnostic
      test to detect emergency metabolic problems in diabetic patients, such as
      diabetic ketosis or ketoacidosis.

PMID- 15554357
TI  - Contribution of cholesteryl ester transfer protein and lecithin:cholesterol
      acyltransferase to HDL size distribution.
AB  - High-density lipoproteins (HDL) includes a heterogeneous class of lipoproteins
      grouped into various subclasses that seem to have different antiatherogenic
      function. Cholesteryl ester transfer protein (CETP) and lecithin cholesterol
      acyltransferase (LCAT) play an active role in HDL remodeling. This study was
      designed to define the role of CETP and LCAT activities on HDL-cholesterol (HDL
      C) plasma levels and HDL size distribution, as determined by nondenaturating
      polyacrylamide gradient gel electrophoresis in 47 clinically healthy Mexican
      individuals without personal and family history of coronary heart disease.
      Surprisingly, plasma activities of CETP (29+/-4.1% of transfer) and LCAT (4.8+/
      2.2% of esterification) did not correlate either with HDL-C plasma levels or with
      any other lipid parameter, indicating the poor contribution of these proteins to
      the lipid profile. The CETP activity showed a negative correlation with small
      HDL3b (r = -0476, P < 0.05), whereas LCAT was positively associated with this HDL
      subclass (r = 0.466, P < 0.05). The LCAT showed a negative correlation with large
      HDL2a (r = - 0.674, P < 0.005). Nevertheless, when the LCAT/CETP ratio was
      calculated, we observed that the higher the ratio, the greater the relative
      proportion of small HDL3b (r = 0.551, P < 0.05) and HDL3c (r = 0.477, P < 0.05).
      These results suggest that the balance of LCAT and CETP activities have a great
      impact in the plasma HDL size distribution.

PMID- 15554358
TI  - Association between chronic fatigue syndrome and the corticosteroid-binding
      globulin gene ALA SER224 polymorphism.
AB  - Chronic fatigue syndrome (CFS) is characterized by idiopathic fatigue of greater
      than 6 months' duration with postexertional exacerbation and many other symptoms.
      A trend toward relative hypocortisolism is described in CFS. Twin and family
      studies indicate a substantial genetic etiologic component to CFS. Recently,
      severe corticosteroid-binding globulin (CBG) gene mutations have been associated
      with CFS in isolated kindreds. Human leukocyte elastase, an enzyme important in
      CBG catabolism at inflammatory sites, is reported to be elevated in CFS. We
      hypothesized that CBG gene polymorphisms may act as a genetic risk factor for
      CFS. A total of 248 patients with CFS defined by Centers for Disease Control
      criteria, and 248 controls were recruited. Sequencing and restriction enzyme
      testing of the CBG gene coding region allowed detection of severe CBG gene
      mutations and a common exon 3 polymorphism (c.825G-->T, Ala-Ser224). Plasma CBG
      levels were measured in 125 CFS patients and 198 controls by radioimmunoassay.
      Total and free (calculated and measured) cortisol levels were ascertained in
      single samples between 8-10 a.m. The age of onset (mid 30s) and gender ratio
      (2.2:1, female:male) of the patients were similar to those reported in U.S.
      epidemiologic studies. A trend toward a preponderance of serine224 homozygosity
      among the CFS patients was noted, compared with controls (chi2 = 5.31, P = 0.07).
      Immunoreactive-CBG (IR-CBG) levels were higher in Serine/Alanine (Ser/Ala) than
      Ala/Ala subjects and higher again in Ser/Ser subjects, this effect was strongest
      in controls; Ser/Ser: 46.1+/-1.8 (n = 31, P = 0.03) vs. Ser/Ala: 42.4+/-1.0 (n =
      56, P = 0.05) vs. Ala/Ala: 40.8+/-1.7 microg/mL (n = 21). Despite higher CBG
      levels, there was a nonsignificant trend toward lower total and free plasma
      cortisol in serine allele positive patients, total cortisol: Ser/Ser: 13.3+/-1.4
      (n = 34) vs. Ser/Ala: 14.0+/-0.7 (n = 66) vs. Ala/Ala: 15.4+/-1.0 (n = 23).
      Homozygosity for the serine allele of the CBG gene may predispose to CFS, perhaps
      due to an effect on hypothalamic-pituitary-adrenal axis function related to
      altered CBG-cortisol transport function or immune-cortisol interactions.

PMID- 15554359
TI  - Residues 34-39 in the thyrotropin receptor are not the target of autoantibodies
      from sera of patients with Graves' disease.
AB  - The thyrotropin receptor (TSHR) and alphal-antytripsin contain a fragment of
      sequence composed of 6 amino acids in which 5 residues are identical. Previously,
      we have suggested that this region of similarity [residues 34-39: (EEDFRV) in
      TSHR] is not the target for Graves' disease patients' autoantibodies. To verify
      this suggestion, we studied the reaction of patients' sera with alphal
      antitrypsin. Two methods were used: TRAK assay, normally designed to estimate
      anti-TSHR autoantibodies in patients' sera, and immunoblotting. A modified
      version of the former assay was also used to study the influence of the synthetic
      peptide, corresponding to the region of similarity in TSHR, on Graves' patients
      sera or on thyrotropin (TSH) binding, and to study the influence of this peptide
      antiserum on TSH binding to the receptor. The TSHR stimulating and blocking
      activity of antisera to this peptide was studied in transfected Chinese hamster
      ovary cells. No influence of alphal-antitrypsin on the binding of patients'
      antibodies to the receptor were noticed nor were there reactions of
      autoantibodies with alphal-antitrypsin. We found that patients with anti-TSHR
      autoantibodies had a normal concentration of alphal-antitrypsin. A peptide
      corresponding to residues 34-39 did not influence Graves' patients sera and TSH
      binding and antiserum to this peptide did not influence TSH binding and adenylate
      cyclase activity. In summary, the results indicated that the sequence EEDFRV is
      not the target for patients autoantibodies.

PMID- 15554360
TI  - Allelic frequency of the PAI-1 4G/5G promoter polymorphism in patients with type
      2 diabetes mellitus and lack of association with PAI-1 plasma levels.
AB  - Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with
      obesity, indicating that adipocytes might influence PAI-1 plasma levels. In
      addition, the 4G/5G promoter polymorphism of the PAI-1 gene possibly modulates
      PAI-1 gene transcription and, as a consequence, PAI-1 plasma levels. Metabolic
      parameters, diabetes complications, PAI-1 plasma levels, and PAI-1 promoter
      genotypes were determined and were tested for correlation in 547 Caucasian
      patients with type 2 diabetes. Genotyping was performed by using allele-specific
      PCR, and PAI-1 plasma levels were measured in 547 well-characterized subjects
      with type 2 diabetes. The allelic frequencies of the polymorphism (0.56 for the
      4G-genotype, 0.44 for the 5G-genotype) were not different from those observed in
      nondiabetic controls. The PAI-1 concentration was positively associated with MI,
      but not with the 4G/5G polymorphism. Statistical analysis of metabolic
      parameters, diabetic complications, and the 4G/5G polymorphism revealed that
      serum fibrinogen levels were significantly higher in the 4G/4G subgroup compared
      with the 4G/5G and 5G/5G subgroups. The correlation between serum fibrinogen and
      4G allele remained significant, even when additional variables, such as gender,
      age, BMI, duration of diabetes, and HbA1c, were controlled. In patients with type
      2 diabetes mellitus, the PAI-1 4G/5G promoter polymorphism does not predict PAI-1
      plasma levels and is not associated with common metabolic parameters besides
      fibrinogen levels.

PMID- 15554361
TI  - Intranasal delivery of recombinant human parathyroid hormone [hPTH (1-34)],
      teriparatide in rats.
AB  - The aim of this study was to explore the nasal route as an alternative to daily
      subcutaneous injections of hPTH (1-34). Anesthetized rats were surgically
      prepared and nasally dosed with aqueous solutions of hPTH (1-34). Plasma samples
      were assayed by radioimmunoassay and data generated fit to two-(intravenous) and
      one-(intranasal) compartment pharmacokinetic models using WinNonlin. The toxicity
      of hPTH (1-34) solution administered to the rats was assessed by screening its
      effect on transepithelial electrical resistance, potential difference,
      paracellular marker permeation, tissue viability, and protein leakage using the
      EpiAirway tissue model. The intranasal absorption of hPTH (1-34) was rapid; the
      absorption rate constants (alpha) were 33.2+/-24 h(-1) [without bovine serum
      albumin (BSA)] and 9.8+/-5.1 h(-1) (with 1% BSA). The maximum plasma
      concentrations (Cmax): 151+/-24 pg/mL (without BSA) and 176+/-37 (with 1% BSA)
      were attained within approximately 15 min. The intranasal bioavailabilities
      (Fabs) were 12.1+/-3.4% (without BSA) and 17.6+/-1.5% (with 1% BSA). The hPTH (1
      34) formulation administered to the rats had no detrimental effect on the
      EpiAirway tissue epithelial electrical parameters and functional integrity. Based
      on the results of this study, the nasal route appears to be a prospective
      alternative to subcutaneous injections of hPTH (1-34).

PMID- 15554363
TI  - Effect of thyroid function on LDL oxidation in hypothyroidism and
      hyperthyroidism.
AB  - Oxidized low-density lipoproteins (LDL) are highly suspected of initiating the
      atherosclerosis process. Hypothyroidism is frequently associated with
      hypercholesterolemia and carries increased risk for atherosclerosis. In contrast
      to hypothyroidism, hyperthyroidism is not associated with increased LDL
      cholesterol, but is associated with increased oxidized LDL. This study was
      designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism
      or hyperthyroidism, and to reveal the effects of treatment in hypothyroidism and
      hyperthyroidism on LDL oxidation and lipid profiles. Thirty-two patients with
      hypothyroidism and 16 patients with hyperthyroidism were studied before the
      therapy and thereafter, when they were euthyroid with appropriate treatment.
      Plasma lipids and lipoproteins, and the oxidizability of LDL by determining the
      levels of malonaldehyde bis (dimethyacetyl) (MDA) and diene conjugation, were
      determined at baseline and after the patients were rendered euthyroid. The actual
      content of dienes in LDL particles was increased in hypothyroidism, with a
      decrease after T4 supplementation (p < .001). Dienes in LDL particles were
      increased in hyperthyroidism, with a decrease after treatment (p < .05). In
      hypothyroid patients, the lag phase was shorter in the pretreatment period than
      in the euthyroid period (p > .05). The lag phase of hyperthyroid patients was
      shorter in the pretreatment period than in the euthyroid period and hypothyroid
      state (p < .001). The Cu2+-catalyzed dienes of LDL and MDA oxidation in the
      hypothyroid state and the subsequent euthyroid states were decreased (p < .001).
      The Cu2+-catalyzed dienes of LDL (p < .01) and MDA oxidation (p < .001) in
      hyperthyroid patients after treatment were decreased. The enhanced LDL oxidation
      may play a role in the cardiac disease process in both hypothyroidism and
      hyperthyroidism.

PMID- 15554362
TI  - Effects of vitamin supplementation on PCB (Aroclor 1254)-induced changes in
      ventral prostatic androgen and estrogen receptors.
AB  - The objective of this study was to determine the impact of the polychlorinated
      biphenyl (PCB) Aroclor 1254 and vitamin C and E on ventral prostatic testosterone
      and estradiol receptor concentration. A group of 30 rats were treated with
      Aroclor 1254 [2 mg/kg body weight (bwt) /day/ip] for 30 days; 10 rats were
      treated as Aroclor 1254 control. The remaining 20 rats were subdivided into the
      following two subgroups of 10 animals each. One group was given vitamin C (500
      mg/kg bwt/day/oral) for 10 days, whereas the other group was given vitamin E (50
      mg/kg bwt/day/oral) for 10 days. Separate controls were also maintained. Ventral
      prostatic androgen and estrogen receptor concentration in all the groups were
      quantified. Serum hormonal profiles such as total T3, T4, TSH, testosterone, and
      estradiol were also estimated in all the groups. Ventral prostatic zinc content
      and serum zinc concentration were also determined in all the groups. Aroclor 1254
      exposure decreased the concentration of both receptors. Decreased serum total T3,
      T4, testosterone, estradiol, and increased TSH were observed after Aroclor 1254
      exposure. Serum and tissue zinc levels were also decreased. Administration of
      vitamin C or E restored both the receptor concentration and the serum hormone
      levels with the exception of estradiol. Administration of vitamin C or E restored
      zinc levels. Vitamin E was more sensitive on ventral prostatic androgen receptors
      and zinc levels, including serum, in PCB-exposed rats.

PMID- 15554364
TI  - The relation between serum leptin levels and max VO2 in male patients with type I
      diabetes and healthy sedentary males.
AB  - This study aimed at investigating leptin levels in male diabetes type I patients
      who were on insulin treatment and also healthy sedentary males. The study
      included 10 male type I diabetes patients and 17 healthy sedentary males. Leptin
      levels of type I diabetes patients and healthy sedentary males with body mass
      index (BMI) over 25 kg/m2 were evaluated separately. The relation between serum
      leptin, max VO2, blood lactic acid levels before and after exercise, and effort
      durations of participants were investigated. At the end of the tests, no
      difference was found between leptin levels, max VO2 values, lactic acid values
      before exercise, and test durations of male type I diabetes patients and healthy
      sedentary males (p > .05), whereas lactic acid levels after exercise were found
      to be lower in healthy sedentary males (p < .05). Leptin levels in the group with
      BMI above 25 kg/m2 were higher than those in the group with BMI below 25 kg/m2 (p
      < .001). It was also seen that max VO2 values and test durations were higher in
      the group with BMI below 25 kg/m2 (p < .05). In conclusion, leptin levels of male
      type I diabetes patients are close to those of healthy sedentary males. The
      increase in leptin levels in both groups is in proportion to the BMI of
      individuals.

PMID- 15554365
TI  - [The distribution of HLA alleles class I and class II among patientes with
      psoriatic arthritis in Croatia].
AB  - The aim of the present study was to analyze the distribution of HLA-A, -B, -Cw,
      and -DRB1 alleles among patients with psoriatic arthritis (PsA) in Croatia. DNA
      was isolated from peripheral blood of 58 PsA patients (28 male and 30 female) and
      tested by PCR-SSP (Polymerase Chain Reaction - Sequence Specific Primers) method
      for polymorphism of the above mentioned HLA loci. The strongest association
      between psoriatic arthritis and HLA in the Croatian population was observed for
      alleles at HLA-B locus (B*39 and B*57), while the association of B*27 and B* 13
      alleles with PsA reached significance only before correction of p value with the
      number of tested alleles. Higher frequency of Cw*02 and DRB1*16 alleles is a
      result of linkage disequilibrium between these alleles and HLA-B alleles
      associated with PsA in Croatia. We also observed lower frequency of B*0702, B*18
      and B*38 alleles in our group of patients.

PMID- 15554366
TI  - [Standardisation proposal for monitoring rheumatoid arthritis patients in
      Croatia].
AB  - Monitoring of outcome measures is carried out because of the assessment of
      medical care quality, also in scientific researches i.e. clinical trials.
      However, it is rarely carried out in daily clinical practice due to lack of time.
      Our goal was to choose the outcome measures set for monitoring disease activity
      in rheumatoid arthritis (RA) which encompasses validity, reliability and
      sensitivity and also primarily satisfies feasybility criteria in daily clinical
      practice. We have analyzed the following parametres in 83 unselected patients
      with RA diagnosis in our department: the mutual relation of single measures of
      the disease activity (Ritchie index, number of swollen joints, general health
      status assessment with VAS and SE), their relation to the DAS and HAQ and the
      relation between the DAS and HAQ. We have recently replaced the Ritchie index by
      28DAS, and HAQ by mHAQ. The values of correlation between the single measures of
      the disease activity which we had found out by statistical processing justify
      their usage in assessment of the clinical status, however the non-existence of
      the correlations compared to HAQ points to unreliability when used in evaluation
      of the disease activity. Unlike the single measures, DAS has positive correlation
      compared to HAQ. Based on our experience in past two years and recommendations
      found in literature, we suggest introducing the outcome measures set for
      monitoring disease activity in rheumatoid arthritis in clinical care. That would
      be mHAQ as the long-term outcome in measuring the disease activity and parametres
      by which DAS28 (number of tender joints, number of swollen joints, general health
      status assessment by VAS, SE) can be calculated as short-term outcome.

PMID- 15554367
TI  - [Primary Sjogren's syndrome and hypokalaemic paralysis--case report].
AB  - We report a case of hypokalaemic quadriparesis in 31-year old woman in whom the
      discovery of distal renal tubular acidosis led to the diagnosis of primary
      Sjogren's syndrome. Hypokalaemic paralysis as initial manifestation of primary
      Sjogren's syndrome is rare, but when it occurs it may precede symptoms of
      xerostomia and xerophthalmia. The diagnosis of primary Sjogren's syndrome should
      be considered in young women who present with progressive weakness, hypokalaemia
      and metabolic acidosis.

PMID- 15554368
TI  - [Weekly and daily intake of alendronate: comparison of tolerance in osteoporosis
      treatment].
AB  - In this study we analyzed, considering complains of patients, tolerance of taking
      alendronate 70 mg once a week in comparison with daily intake of alendronate 10
      mg. Subjects were patients that were treated for osteoporosis at Department for
      physical medicine and rehabilitation in Clinical hospital Dubrava. The diagnosis
      of osteoporosis was established by DXA densitometry. Pains in oesophagus were the
      main reason for ceasing of use of alondronate. According to our research patients
      tolerate taking alendronate 70 weekly 4,22 times better than alendronate 10
      daily.

PMID- 15554369
TI  - Epidemiology and diagnostics of primary Sjogren's syndrome.
AB  - This review paper contains selected aspects of Sjogren's syndrome. It consists of
      epidemiology, ultrasound of salivary glands and antimuscarinic antibodies. The
      first part present studies aimed to determine the prevalence and the incidence of
      the disease with special emphasize on epidemiological studies performed in
      Slovenia. This is followed by the demonstration of the role of ultrasound of
      salivary glands in the diagnosis of Sjogren's syndrome and the value of
      antimuscarinic antibodies in global assesment of the secretory failure.

PMID- 15554370
TI  - [Classification and pathogenensis of spondyloarthropathies].
AB  - The classification and pathogenesis of spondyloarthropathies are presented.

PMID- 15554371
TI  - [Early diagnosis of axial spondyloarthropaties].
AB  - Spondyloarthropaties are the group of seronegative inflammatory rheumatic
      diseases affecting axial and perpendicular skelet. Most of the patients belong to
      the work active population and the longterm prognosis and outcome is poor. The
      diagnosis of ankylosing spondylitis is delayed over years, sometimes decades. Our
      perception of spondyloarthropaties todays is changing. Early diagnosis and
      agressive treatment could influence to prognosis and outcome. For these purposes
      we have new diagnostic techniques and new potent drugs.

PMID- 15554372
TI  - [Extraskeletal manifestations of seronegative spondyloarthropathies].
AB  - Spondyloarthropathies constitute a cluster of interrelated and overlapping
      chronic inflammatory rheumatic diseases of unknown etiology that include
      ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic
      arthritis and undifferentiated spondyloarthritis. These diseases are not
      associated with rheumatoid factor, they occur in genetically predisposed
      individuals and show a strong association with HLA-B27. The primary pathologic
      sites include the entheses, the sacroiliac joints and the axial skeleton with or
      without some nonarticular structures, such as the skin, eye, aortic valve, heart
      and kidney.

PMID- 15554373
TI  - [Pharmacotherapy for spondyloarthropathies].
AB  - Since decade ago spondyloarthropathies (SpA) were neglected group of rheumatic
      disorders because of narrow therapeutic window. Main managing principles are
      described with emphasis to the assement of disease activity and distribution of
      pathological changes. Nonsteroidal antirheumatic drugs (NSAID) and physical
      therapy are still cornerstone for axial disease. Sulphasalzine and methotrexate
      are first choice considering peripheral arthritis. Biologic agents are effective
      in active vertebral and extravertebral disease. Local corticosteroid injection is
      favourable method for enthesitis and oligoarthritis and systemic treatment is
      indicated in patients during flare up of inflammation. Pamidronate and thalidomid
      are potential new agents for refractory cases.

PMID- 15554374
TI  - [Spondyloarthropathies--clinical evaluation and physical therapy].
AB  - Spondyloarthropathy is a group of chronic autoimmune disorders including
      ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis
      associated with inflammatory bowel disease, acute anterior uveitis and
      undifferentiated spondyloarthropathies. The spondyloarthropathies share common
      clinical, radiological, and genetic features that are clearly distinct from other
      inflammatory rheumatic diseases. The major goal in the management of patients
      with rheumatic disorders is to control or cure the disease and to preserve and
      control function and health status. To measure treatments' efficacy standardized
      assessment of organ morphology, function, and of health status are required. The
      instruments for measuring health status or quality of life cover a variety of
      dimensions of health, including physical, social, and emotional functioning.
      Measurements used to evaluate the efficacy of treatments in ankylosing
      spondylitis include spinal and chest movement, duration and severity of morning
      stiffness, and quality of sleep. Health status indices such as the HAQ or AIMS
      are not readily applicable to spondyloarthropaties. It is reason to use some
      others: 1. Functional status measure S-HAQ for patients with spondylitis by
      adding five items to the HAQ, to cover the activities identified as most
      problematic; 2. Functional index for the assessment of ankylosing spondylitis
      (Dougados Functional Index - DFI) - it is valid and reliable and shows sufficient
      responsiveness; S-HAQ appears at least as sensitive to change as the Dougados
      Index; 3. The Leeds Disability Questionnaire assesses disability in ankylosing
      spondylitis, inquiring about four areas of function: mobility, bending down,
      reaching up and neck movements, and postures; 4. The Bath Ankylosing Spondylitis
      Functional Index (BASFI) 10 item self-administered questionnaire to assess
      function and activities of daily living in patients with ankylosing spondylitis.
      Physical therapy is one of the most important way to restore function and health
      status in patients with spondyloarthropathies, esspecially individual
      kinesitherapy. We use and many other procedures combine them with kinesitherapy
      (ultrasound, cryotherapy, electrotherapy, laser ...).

PMID- 15554375
TI  - [Hip in rheumatic diseases].
AB  - The clinical diagnosis of hip pain is based on functional anatomy knowledge,
      detailed medical history and careful physical examination of the joints,
      periarticular soft tissue, nerve and blood supply, abdomen and thoracolumbal
      spine. Pain in the hip region may arise from the hip itself, adjacent bones or
      periarticular soft tissue and in addition thoracolumbal spine disorders,
      intraabdominal pathologies and peripheral vascular diseases can present with
      reffered pain in this region. Pain is the main symptom and it can be accompanied
      with morning stiffness and presence of systemic symptoms such as fatique, fever,
      weight loss or worsening of pain at night. Althought the technology for
      diagnostic testing is well developed, a detailed history is still as well as
      careful physical examination, essential for the precise diagnosis.

PMID- 15554376
TI  - [Hip in inflammatory rheumatic diseases].
AB  - The hip changes in inflammatory rheumatic diseases are presented.

PMID- 15554377
TI  - [Imaging methods of examining the hip joint].
AB  - The hip joint is a synovial joint of the appendicular skeleton which constituents
      of articular cartilage, subchondral bone plate, articular capsule synovial
      membrane which produces synovial fluid. Ankylosing spondylitis is chronic
      inflammatory disorder of unknown cause that affects the axial and appendicular
      skeleton. Alterations occur in synovial and cartilaginous joints and sites of
      tendon and ligament attachment to bone.

PMID- 15554378
TI  - [The hip in musculoskeletal disorders--nonsurgical management].
AB  - Basic principles of nonsurgical management of hip diseases encountered in most
      frequent rheumatic conditions are described. Non-pharamacologic therapy like
      correction of predisposing factors, weight reduction in the obese patients and
      correction of valgus and varus knee deformities are emphasised. Individually
      prescribed rehabilitation and education assissts the patient in reaching his or
      her maximal potential. Nonsteroidal antiinflammatory drugs (NSAR) are the drugs
      of first choice in pharmacological management. They are widely used; in low
      dosages NSAR are effective analgesics; in higher dosages, they have anti
      inflammatory activity.

PMID- 15554379
TI  - [Compression vertebral fracture in osteoporosis--prevention and treatment].
AB  - Vertebral fractures are the earliest and most common osteoporotic fractures.
      Usually vertebral fractures are associated with following clinical symptoms: back
      pain, posture change, loss of height, functional impairment, disability and
      decreasing quality of life. After 3 years of treatment raloxifene reduced the
      risk of first vertebral fracture by 55%. The fracture risk within one year was
      reduced by as much as 68%. The continued observation proved its sustained
      efficacy in further reduction of the fracture risk by 50% in the fourth year.

PMID- 15554380
TI  - CT evaluation of living related liver donors.

PMID- 15554381
TI  - Case of the month. Rounded atelectasis in a patient with asbestos-related pleural
      disease.

PMID- 15554382
TI  - Mediastinal aspergilloma: a rare manifestation of a common infection with CT and
      pathologic correlation.
AB  - Extra-pulmonary thoracic aspergilloma is an unusual pathologic manifestation of
      this organism. We present a case manifesting as a mediastinal mass on chest CT
      causing some diagnostic difficulty and requiring surgical resection.

PMID- 15554383
TI  - CT characteristics of primary retroperitoneal neoplasms.
AB  - Primary retroperitoneal neoplasms account for only 0.1-0.2% of all malignancies.
      Retroperitoneal neoplasms are most commonly mesodermal, neurogenic or lymphatic
      in origin, with lymphoma, liposarcoma, leiomyosarcoma and malignant fibrous
      histiocytoma the vast majority of malignant primary retroperitoneal tumors.
      Although the radiographic features of retroperitoneal neoplasms often overlap,
      certain CT characteristics, pattern of spread and specific tumor prevalence among
      different demographic groups can help suggest the tumor type. CT is used to
      diagnosis and assess the size and extent of retroperitoneal tumors, as well as
      assess the involvement of organs and vasculature with resection in mind.

PMID- 15554384
TI  - Nerve growth factor stimulates MMP-2 expression and activity and increases
      invasion by human pancreatic cancer cells.
AB  - Pancreatic cancer frequently invades and migrates along neural tissue. Although
      the exact mechanisms are unknown, perineural invasion negatively impacts
      prognosis for pancreatic cancer patients. Matrix metalloproteinases (MMPs) are
      overexpressed in pancreatic cancer and are associated with poor prognosis. We
      hypothesized that nerve growth factor (NGF) released from neural tissue increases
      the invasive properties of pancreatic cancer cells. In the present study we
      investigated the effect of NGF on the expression and activity of MMP-2 in human
      pancreatic cancer cells. NGF dose dependently increased MMP-2 protein in the
      culture medium and stimulated MMP-2 gelatinolytic activity. This effect was
      mediated by specific binding of NGF to its receptor trk A, which was detected on
      all pancreatic cancer cells, with subsequent activation of the p44/42 MAPK
      signaling pathway. The NGF-induced increase in MMP-2 expression and activity lead
      to an enhanced invasion in vitro. These findings support the hypothesis that
      neurotrophic factors, e.g., NGF, are critically involved in mediating perineural
      invasion of pancreatic cancer.

PMID- 15554385
TI  - Critical regulation of genes for tumor cell migration by AP-1.
AB  - The AP-1 transcription factor plays a critical role in regulating tumor cell
      proliferation and has been implicated in controlling a program of gene expression
      that mediates cell motility and invasion in vitro. We have utilized two dominant
      negative AP-1 constructs, TAM67 and aFos, each fused to GFP, to investigate the
      role of AP-1 complexes in an invasive, clinically derived human tumor cell line,
      HT-1080. As expected, high levels of both GFP-TAM67 and GFP-aFos arrested HT-1080
      cells in the G1 phase of the cell cycle. Strikingly, at low levels GFP-aFos, but
      not GFP-TAM67, caused a change in colony morphology, impairment of directional
      motility in a monolayer wound healing assay, as well as inhibition of chemotaxis
      and haptotaxis. Microarray analysis identified a novel set of AP-1 target genes,
      including the tumor suppressor TSCL-1 and regulators of actin cytoskeletal
      dynamics, including the gelsolin-like actin capping protein CapG. The
      demonstration that AP-1 regulates the expression of genes involved in tumor cell
      motility and cytoskeletal dynamics in a clinically derived human tumor cell line
      identifies new pathways of control for tumor cell motility.

PMID- 15554386
TI  - Regression of bone metastases following adoptive transfer of anti-CD3-activated
      and IL-2-expanded tumor vaccine draining lymph node cells.
AB  - As many as 80% of patients with breast, prostate, or lung cancer develop bone
      metastases during the course of their illness. However, thus far, no attempts
      have been made to explore the potential value of adoptive immunotherapy with
      antigen-specific T lymphocytes specifically for the treatment of skeletal
      metastases. Here, we demonstrate tumor regression in a preclinical model of bone
      metastases from the murine B16BL6 melanoma following adoptive transfer of
      effector T lymphocytes obtained from tumor vaccine draining lymph nodes. The
      antitumor effect required transfer of high number of effector cells, which was
      dependent on CD8+ cells as demonstrated by in vivo depletion of different T cell
      subsets, and was magnified if effector cells were administered to the arterial
      supply of the bone/bone marrow. Using flow cytometric analysis, CFSE-labelled
      Thy1.1+ donor T cells were isolated from the bone marrow of tumor-bearing mice at
      24 h and 6 days following adoptive transfer. At the latter time point cell
      division of the transferred effector cells was detectable. Currently, no curative
      treatment is known for skeletal metastases in clinical practice. Considering the
      promising early findings in the present study, further studies exploring the
      therapeutic potential of adoptive immunotherapy for metastatic disease to the
      skeleton are warranted.

PMID- 15554387
TI  - Marrow-derived mesenchymal stem cells: role in epithelial tumor cell
      determination.
AB  - Marrow stroma represents an advantageous environment for development of
      micrometastatic cells. Within the cellular structure of marrow stroma,
      mesenchymal stem cells (MSC) have been postulated as an interacting target for
      disseminated cancer cells. The studies reported here were performed to gain more
      information on the interaction of the human breast cancer cell line MCF-7 with
      human bone marrow-derived MSC cells and to investigate whether this interaction
      affects tumor cell properties. The results showed that after co-culture with MSC,
      changes were detected in the morphology, proliferative capacity and aggregation
      pattern of MCF-7 cells, but these parameters were not affected after the co
      culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10.
      Since the indirect culture of MCF-7 with MSC or its products also resulted in
      functional changes in the tumor cells, we evaluated whether these effects could
      be attributed to growth factors produced by MSC cells. It was found that VEGF and
      IL-6 mimic the effects produced by MSC or its products on the proliferation and
      aggregation properties of MCF-7, cells, respectively. Thus, it seems that after
      entry of disseminated tumor cells into the marrow space, their proliferative and
      morphogenetic organization patterns are modified after interaction with distinct
      stromal cells and/or with specific signals from the marrow microenvironment.

PMID- 15554388
TI  - Expression of MUC1 recognized by monoclonal antibody MY.1E12 is a useful
      biomarker for tumor aggressiveness of advanced colon carcinoma.
AB  - To address the need for new prognostic parameters in advanced colon carcinoma
      that could add insights into the aggressiveness of tumors, the expression levels
      of MUC1 recognized by a monoclonal antibody (mAb) MY.1E12 in archival specimens
      from 123 Japanese patients with colon carcinomas were evaluated by
      immunohistochemistry to correlate the results with clinicopathological
      characteristics. The localization of mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1) was
      classified into apical, cytoplasmic and stromal types based on the predominant
      cellular distribution. The MUC1 mRNA levels revealed by in situ hybridization
      were not a determinant for the localization types of MY.1E12-MUC1. Immunostaining
      of MY.1E12-MUC1 was recognized in the cancerous epithelia of pT1 carcinoma in
      61%, pT2 in 78%, pT3 in 98% and pT4 in 90% of the cases at the deepest invading
      sites. At the deepest invading sites, apical-type localization was found to
      predominate in pT1 carcinoma, but stromal-type localization was found to increase
      in pT2-4 carcinomas in parallel with the depth of invasion. The frequency of
      synchronous distant organ metastasis at the time of diagnosis tended to be higher
      in cases of pT3 and pT4 carcinomas in the stromal-type localization-dominant
      group than in cases in the apical-type localization-dominant group. The post
      surgical survival outcome of cases of pT3 and pT4 carcinomas was significantly
      poorer in the former than in the latter (P = 0.002). The stromal-type
      localization of MY.1E12-MUC1 may be a phenotype serving as a unique biological
      feature associated with the tumor aggressiveness of advanced colon carcinoma.

PMID- 15554389
TI  - Butyrate reduces liver metastasis of rat colon carcinoma cells in vivo and
      resistance to oxidative stress in vitro.
AB  - Injection of the rat colon carcinoma cell line CC531 into spleen of syngeneic
      rats results in considerable amounts of liver metastases within 14 days. We
      investigated whether preincubation of the cells with butyrate reduced their
      metastatic ability in vivo and whether this was accompanied by reduction in
      related properties such as secretion of metalloproteinases and their ability to
      withstand oxidative stress. Butyrate incubation reduced cell growth rate and
      initiated apoptosis in a dose- and time-related manner, but proliferation was
      retrieved when cultivation was continued in medium without butyrate. Splenic
      injection of butyrate treated, proliferating cells resulted in significantly
      reduced amounts of tumor mass compared to untreated cells. The butyrate treated
      cells were more susceptible to oxidative stress than control cells, as
      demonstrated by increased number of apoptotic cells and reduced cell growth after
      exposure to menadione. A reduction in cellular glutathione was found after
      prolonged incubation with butyrate. Butyrate appeared not to alter the secretion
      of active metalloproteinases from the cells although an apparent increase in
      proforms was demonstrated. Neither did butyrate alter the synthesis of
      metalloproteinase inhibitors. Lastly, a reduced adhesion of the tumor cells to
      collagen coated matrix was found after butyrate treatment. Thus, the inhibitory
      effects of butyrate on tumor malignancy are caused by a diversity of mechanisms.

PMID- 15554391
TI  - Development of a green fluorescent protein metastatic-cancer chick-embryo drug
      screen model.
AB  - The chick-embryo model has been an important tool to study tumor growth,
      metastasis, and angiogenesis. However, an imageable model with a genetic
      fluorescent tag in the growing and spreading cancer cells that is stable over
      time has not been developed. We report here the development of such an imageable
      fluorescent chick-embryo metastatic cancer model with the use of green
      fluorescent protein (GFP). Lewis lung carcinoma cells, stably expressing GFP,
      were injected on the 12th day of incubation in the chick embryo. GFP-Lewis lung
      carcinoma metastases were visualized by fluorescence, after seven days additional
      incubation, in the brain, heart, and sternum of the developing chick embryo, with
      the most frequent site being the brain. The combination of streptokinase and
      gemcitabine was evaluated in this GFP metastatic model. Twelve-day-old chick
      embryos were injected intravenously with GFP-Lewis lung cancer cells, along with
      these two agents either alone or in combination. The streptokinase-gemcitabine
      combination inhibited metastases at all sites. The effective dose of gemcitabine
      was found to be 10 mg/kg and streptokinase 2000 IU per embryo. The data in this
      report suggest that this new stably fluorescent imageable metastatic-cancer chick
      embryo model will enable rapid screening of new antimetastatic agents.

PMID- 15554390
TI  - Control of pulmonary metastases of rat mammary cancer by inhibition of uPA and
      COX-2, singly and in combination.
AB  - Tumor cell metastasis can be suppressed by the attenuation of proteolytic and
      angiogenic events that are mediated by tumor and endothelial cells. Combinations
      of specific inhibitors directed to separate stages of the metastatic cascade may
      improve the potential for adjuvant therapies. Amiloride is an effective
      plasminogen activator inhibitor, while celecoxib is a cylcooxygenase-2 inhibitor.
      In vitro invasion assays were used to assess the effect of each inhibitor on the
      cellular invasion of MATB rat mammary carcinoma cells. Individually, both
      amiloride and celecoxib impeded cellular invasion in a dose-dependent manner.
      Combinations consistently exerted a significant inhibitory response (91 to 99%).
      These inhibitors were administered alone and in combination to evaluate their
      efficacy in the prevention of pulmonary metastases from a primary rat mammary
      carcinoma. Amiloride and celecoxib, alone and in combination, consistently showed
      no effect on the growth of primary tumors. The combined inhibitors were able to
      reduce significantly the growth of local recurrences following primary tumor
      excision and metastatic incidence rates. Numbers of pulmonary metastases were
      reproducibly and significantly decreased with the administration of amiloride and
      celecoxib, alone and in combination. Celecoxib alone was most effective with a
      reduction in 98% of the metastases, yet distinctions were observed in the results
      with respect to the local recurrences, blood levels for the inhibitors and tissue
      production of prostaglandin E2. These data demonstrate the potential use for
      celecoxib, alone and in combination with amiloride, in the suppression of
      metastases.

PMID- 15554392
TI  - Expression of MUC1 recognized by a monoclonal antibody MY.1E12 is a useful
      biomarker for tumor aggressiveness of carcinoma of the gallbladder.
AB  - The overall outcome of gallbladder carcinoma has not been favorable because of
      frequent recurrence at distant sites after surgery. A high-level expression of
      MUC1 recognized by a monoclonal antibody (mAb), MY.1E12, is correlated with poor
      survival in several types of carcinomas. There is a need to find new prognostic
      parameters that can give further insights into tumor aggressiveness of the
      disease. Immunohistochemistry was performed to determine the expression level of
      mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1) in 79 cases of gallbladder carcinoma of
      different depths of invasion and to determine the correlation of the expression
      level with clinicopathological findings. The cellular distribution of MY.1E12
      MUC1 was heterogeneous among carcinomas of different depths of invasion.
      Immunohistochemical localization was classified into apical, cytoplasmic and
      stromal types based on the predominant cellular distribution. In 35 cases of pT2
      carcinoma in which curative resections had been performed, the localization was
      apical type in 54%, cytoplasmic type in 66%, and stromal type in 56% of the cases
      at the deepest invading sites in the subserosal layer. Postsurgical recurrences
      at distant sites were seen in 11 of 18 cases of pT2 carcinoma (61%) that had more
      than or equal to 10% of the cancerous epithelia showing stromal localization of
      MY.1E12-MUC1 at the deepest invading sites (stromal group) and in 3 of 17 cases
      (18%) that had less than 10% of the cancerous epithelia showing stromal
      localization (nonstromal group). The postsurgical 5-year survival rate was
      significantly poorer in the former (54%) than in the latter (79%; P = 0.049). In
      38 cases of pT3 and pT4 carcinomas, the frequency of synchronous distant organ
      metastasis at the time of diagnosis was significantly higher in cases in the
      stromal group (61%) than in cases in the nonstromal group (20%). Moreover, in 73
      cases of pT2, pT3 and pT4 carcinomas, the expression rate of abnormal
      localization of E-cadherin was significantly higher in the stromal group (63%)
      than in the nonstromal group (30%). The MUC1 mRNA levels revealed by in situ
      hybridization would not be a determinant important for the stromal localization.
      The stromal localization of MY.1E12-MUC1 may be a phenotype serving as a unique
      biological feature associated with the tumor aggressiveness of gallbladder
      carcinoma, such as the tendency to form distant organ metastasis.

PMID- 15554393
TI  - A BALB/c murine lung alveolar carcinoma used to establish a surgical spontaneous
      metastasis model.
AB  - Line-1, a weakly immunogenic lung tumor cell line derived from the BALB/c mouse,
      metastasizes spontaneously to the lungs of mice following subcutaneous
      administration. The parameters that influence metastasis as well as the
      progression of metastatic lung disease following surgical resection of primary
      subcutaneous tumors were characterized. Histological analysis of the lungs
      obtained from mice bearing different size subcutaneous tumors demonstrated that
      >90% of the mice developed micrometastatic disease in the lungs when the tumor
      exceeded 650 mm3 in size. Surgical resection of subcutaneous tumors resulted in
      the cure of primary disease in 95% of the mice. Macroscopic tumor nodules were
      grossly visible in the lungs of 75% of the mice 5 weeks after surgery. Serum
      amyloid A level correlated with primary tumor burden and was diagnostic for the
      presence of metastatic disease. The efficiency of metastasis, post-surgical
      primary tumor recurrence and long-term survival were significantly different
      between BALB/c mice obtained from different suppliers. The Line-1-BALB/c surgical
      metastasis model provides a clinically relevant tool for the evaluation of anti
      cancer therapies, especially those that are designed to target long-term
      suppression of minimal residual disease following surgical intervention.

PMID- 15554394
TI  - Protein phosphatase-2A maintains focal adhesion complexes in keratinocytes and
      the loss of this regulation in squamous cell carcinomas.
AB  - Studies assessed if the serine/threonine protein phosphatase-2A (PP-2A) maintains
      cytoskeletal integrity of normal keratinocytes and if this differs in malignant
      cells. Murine and human keratinocyte cell lines contained more PP-2A activity
      than did the murine SCC VII/SF squamous cell carcinoma cells or primary cultures
      of human head and neck squamous cell carcinoma (HNSCC) cells. Since tyrosine
      phosphorylation of the focal adhesion proteins paxillin and FAK is indicative of
      more stable focal adhesions, cells were immunostained for phosphotyrosine plus
      either paxillin or FAK, and then examined by confocal microscopy. In non
      malignant keratinocytes, phosphotyrosine staining co-localized with paxillin and
      FAK. This co-localization occurred at the cell periphery in a pattern resembling
      focal adhesions. In contrast, the co-localization of phosphotyrosine with either
      paxillin or FAK along the cell periphery was almost absent in the SCC cells or in
      keratinocytes that were treated with okadaic acid to inhibit PP-2A activity.
      Consistent with this was a rounded cellular morphology with less extended
      processes as compared to control keratinocytes. These studies indicate PP-2A
      maintains the organization and tyrosine-phosphorylated state of the focal
      adhesion proteins FAK and paxillin, and that the loss of PP-2A activity results
      in a loss of cytoskeletal organization, as is seen in SCC.

PMID- 15554395
TI  - Interceptive management of eruption disturbances: case report.
AB  - The aim of the present report is to describe a case of a patient with eruption
      disturbances of an ankylosed lower primary second molar, delayed development of a
      maxillary permanent canine associated with an odontoma and a class III dental
      malocclusion. In such a case the objectives of treatment are: to prevent
      impaction of the lower second premolar and tipping of the lower first molar; to
      establish correct anterior overbite and overjet and to control the development of
      the permanent upper canine.

PMID- 15554396
TI  - Treatment options for the occlusal surface of first permanent molars.
AB  - Restorative dentistry has been increasingly concerned with preservation of the
      dental structure. For that reason, ultraconservative cavity preparations have
      been performed with air abrasion systems. The aim of this study was to present
      treatment options for the occlusal surface of first permanent molars with
      employment of the conventional method and the air abrasion system for
      accomplishment of the cavity preparation and a composite occlusal matrix for an
      accurate reproduction of the tooth surface.

PMID- 15554397
TI  - TMJ internal derangement treatment in the growing patient: effect of functional
      appliance therapy on condyle and fossa relocation.
AB  - New biodynamic factors seem to be involved on condyle and fossa remodeling and
      relocation, conditioning to mandibular growth direction, size and morphology. The
      understanding of the mechanism of action is critical for treatment of TMJ
      dysfunction in children and youths for those who hope to treat and retain the
      achieved correction during growth. The purpose of this article is to describe a
      specific, non-muscular hypothesis that explains the way the condyle modifies and
      the fossa remodels and relocates to achieved a new therapeutic, stable position,
      creating an anatomical base for long-term retention of the results. A case report
      of a young patient will be illustrated and available clinical data will be
      discussed.

PMID- 15554398
TI  - Gummy smile: clinical parameters useful for diagnosis and therapeutical approach.
AB  - In the analysis of the characteristics of a pleasant smile, a gummy smile has
      negative components, which most affect the esthetics of non-verbal communication.
      For this purpose a proposed classification based upon etiopathogenetic criteria
      as useful indications for a therapeutical approach is given. The nature of a high
      smile line can be: dento-gingival, connected to an abnormal dental eruption,
      which is revealed by a short clinic crown; muscular, caused by an hyperactivity
      of the elevator muscle of the upper lip; dento-alveolar (skeletal), due to an
      excessive protuberance or vertical growth of the jawbone (maxillary); lastly, a
      mixed nature, in the presence of more than one of the above described factors The
      diagnosis of gummy smile must be precocious and based, with reference to specific
      parameters, upon a careful analysis of the etiopathogenetic factors and the
      degree of seriousness of the alteration. A correct treatment plan must
      contemplate the possibility of an orthognatodontic, orthopedic and/or surgical
      therapeutic resolution considering the seriousness and complexity of the gums
      exposures (high smile line) in connection with the age of the subject.

PMID- 15554400
TI  - Orthodontic assisted tooth eruption in a dentigerous cyst: a case report.
AB  - In an orthodontic practice, it is common to deal with impacted teeth, which are
      one of the most difficult situations dealt with by dentists. This case report
      describes the surgical and orthodontic management of the impacted teeth in a
      large dentigerous cyst. In the initial stage of treatment, the cyst was
      marsupialized over 7 months. After decompression of the cyst, spontaneous
      eruptions of the impacted tooth were noticed. Then, they were orthodontically
      brought into the proper occlusion.

PMID- 15554399
TI  - Aggressive periodontitis of the primary dentition associated with idiopathic
      immune deficiency: case report and treatment considerations.
AB  - The present case, of a child with an idiopathic immune deficiency and aggressive
      periodontitis in the primary dentition, serves as an example for the treatment
      considerations in these cases. Extraction of all the primary teeth proved to be
      the most adequate treatment. It allowed the child to eat properly and prevented
      unwanted infections that could endanger the life of the child. The newly erupted
      permanent teeth have been subjected to careful oral hygiene, clorhexidine topical
      applications, and have mild gingival inflammation and no attachment loss.

PMID- 15554401
TI  - Unusual case of multiple natal teeth.
AB  - Natal teeth are defined as teeth that are present in the mouth at the birth, and
      the occurrence is rare. In the literature, few reports have described cases with
      involved multiple elements. This article describes an unusual case of a newborn
      with eleven natal teeth that belong to the primary dentition and the therapy
      utilized.

PMID- 15554402
TI  - Natal maxillary primary molars: case report.
AB  - An unusual case of a newborn with two immature natal maxillary molars is
      presented. Clinical and histological examination showed that the teeth were
      rootless and incompletely mineralized. The patient was followed up during one
      year and we confirmed that the natal teeth were from normal primary series.

PMID- 15554403
TI  - Regional odontodysplasia: report of a case.
AB  - Regional odontodysplasia is a rare developmental anomaly involving both
      mesodermal and ectodermal dental components in groups of contigous teeth. RO
      affects the primary and permanent dentition in the maxilla and mandible or both
      jaws. Generally, it is localized in only one arch. The maxillary arch is affected
      more often than the mandibular arch. The affected teeth tend to be in a
      consecutive series that does not cross the midline, although some cases do not
      follow this pattern, as in the present case, have been documented.
      Radiogaphically wide pulp chambers and thin poorly defined hard tissue outlines
      described as a "ghost teeth" appearance, are typical features. A case of regional
      odontodysplasia in a 5 year old male patient is presented. The clinical and
      radiogaphical findings of this developmental anomaly and treatment are described.

PMID- 15554404
TI  - Ultrasonographic evaluation of effectiveness of circumoral muscle exercises in
      adenotonsillectomized children.
AB  - Mouth breathing due to obstructive adenoids and tonsils has deleterious effects
      on craniofacial morphology especially on dentition and dental arches. Reports
      confirm that removal of nasal obstruction, adenoids and tonsils has not given
      beneficial development of circumoral musculature. Use of muscles to correct
      malocclusion was first recommended by Alfred Paul Rogers. This study highlights
      the imaging of circumoral musculature using ultrasound to evaluate the
      effectiveness of muscle exercises in adenotonsillectomized children. Definite
      changes in muscle thickness were noted in subjects, who were given muscle
      exercises.

PMID- 15554405
TI  - Electromyographic activity of perioral muscle in breastfed and non-breastfed
      children.
AB  - The objective was to verify the electrical activity of the Mm. orbicularis oris
      and mentalis during suction of different liquids in breastfed and non-breastfed
      children from 2.5-3.5 years old. It was used a signal conditioner (MCS-V2-Lynx
      Eletronica Ltda, SP, BR) and Beckman Ag-AgCl bipolar surface electrodes.
      Breastfed children presented higher activity for mentalis and smaller values for
      the M. orbicular oris than non-breastfed children, suggesting the existence of
      different profiles of muscle activation between them.

PMID- 15554406
TI  - Prevalence of bruxism in children receiving treatment for attention deficit
      hyperactivity disorder: a pilot study.
AB  - The objective of this study was to evaluate reported bruxism among children
      affected by attention deficit hyperactivity disorder (ADHD). Thirty children
      diagnosed with ADHD and 30 healthy age and gender matched controls participated
      in the study. All subjects were examined for dental attrition, and the parents
      were asked for signs and symptoms of bruxism in their children using a
      questionnaire. Prevalence of oral parafunction was evaluated comparing ADHD
      children taking medications, ADHD children not taking medications, and controls.
      Subjects affected by ADHD and pharmacologically treated showed higher occurrence
      of bruxism compared to subjects affected by ADHD not taking medicines and
      controls; and within the ADHD group taking medications, CNS-stimulants have been
      associated with such side effect more frequently than the other drugs.

PMID- 15554407
TI  - Oral granular cell tumors: an analysis of 10 new pediatric and adolescent cases
      and a review of the literature.
AB  - Clinicopathologic studies on the granular cell tumor, a submucosal benign soft
      tissue neoplasm, have not addressed the pediatric and adolescent population. This
      study of patients from birth to 19 years of age describes clinically and
      microscopically 10 new cases and combines them with 24 well-documented pediatric
      cases previously published in the English-language literature. Of the 34, patient
      ages ranged from 3 to 19 years (mean age 14.5 years) with a female-to-male ratio
      of 3.3 to 1. The most common location was the tongue (50%) and lips (25%). In
      neoplasms whose epithelial findings were documented microscopically, a reactive
      pseudoepitheliomatous (pseudocarcinomatous) hyperplasia of the overlying
      epithelium occurred in 29%. The recurrence rate was less than 10% following
      conservative surgical excision. This study reveals that an oral granular cell
      tumor in the first decade of life is an uncommon event and discusses the
      importance of differentiating between squamous cell carcinoma and granular cell
      tumor.

PMID- 15554408
TI  - Ameloblastic fibro-odontoma: a case report.
AB  - Ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumor consisting of
      both ectodermal and mesenchymal components. It occurs predominantly in children
      and adolescents, especially in the mandibular posterior region.
      Histopathologically, AFO exhibits the combination of ameloblastic fibroma-like
      tissue and complex odontoma. A case of AFO in a 1-year-old child was presented.
      It produced an expansile lesion over the upper right anterior region and showed
      typical histopathological features of AFO. She was treated by enucleation with no
      recurrence observed after a follow-up period of 1 year.

PMID- 15554409
TI  - Nasotracheal intubation: an unusual cause of palatal perforation in an insulin
      dependent diabetes mellitus patient.
AB  - A case of palatal perforation occurring in 7-year-old girl with IDDM due to
      nasotracheal intubation is reported. The child, who was not previously diagnosed
      of IDDM, was brought to hospital in comatose stage and was put on nasotracheal
      tube for maintaining respiration. This paper highlights the link between IDDM and
      palatal perforation communicating the nasal cavity due to naso-tracheal
      intubation.

PMID- 15554410
TI  - Paradental cyst: case report and review of the literature.
AB  - The origin of paradental cysts is related to inflammatory processes, especially
      pericoronaritis involving impacted or semi-impacted teeth. The authors present a
      case of paradental cyst related to lower second molar that did not show clinical
      evidence of inflammatory process. The main aspects related to its classification,
      diagnosis and clinical characteristics are also discussed.

PMID- 15554411
TI  - Evaluation of an oral health promotion program using different indicators.
AB  - The purpose of this study was to implement an Oral Health Promotion Program
      (OHPP) and check its effectiveness using different indicators at two different
      times (birth to 10 months after the OHPP). The sample consisted of 325 healthy
      children (6.1 and 11.3 years old). The results indicated that there was a
      statistically significant reduction measured by the three indicators (p<0.001).
      The effectiveness of the OHPP was positive and clearly shown by the oral health
      indicators used.

PMID- 15554412
TI  - Pathophysiology of stroke: lessons from animal models.
AB  - The current pathophysiological understanding of stroke is substantially based on
      experimental studies. Brain injury after cerebral ischemia develops from a
      complex signaling cascade that evolves in an at least partially unraveled
      spatiotemporal pattern. Early excitotoxicity can lead to fast necrotic cell
      death, which produces the core of the infarction. The ischemic penumbra that
      surrounds the infarct core suffers milder insults. In this area, both mild
      excitotoxic and inflammatory mechanisms lead to delayed cell death, which shows
      biochemical characteristics of apoptosis. While brain cells are challenged by
      these deleterious mechanisms, they activate innate protective programs of the
      brain, which can be studied by means of experimentally inducing ischemic
      tolerance (i.e., ischemic preconditioning). Importantly, cerebral ischemia not
      only affects the brain parenchyma, but also impacts extracranial systems. For
      example, stroke induces a dramatic immunosuppression via an overactivation of the
      sympathetic nervous system. As a result, severe bacterial infections such as
      pneumonia occur. Complex signaling cascades not only decide about cell survival,
      but also about the neurological deficit and the mortality after stroke. These
      mechanisms of damage and endogenous protection present distinct molecular targets
      that are the rational basis for the development of neuroprotective drugs.

PMID- 15554413
TI  - Hypoglycemic brain damage.
AB  - Hypoglycemia was long considered to kill neurons by depriving them of glucose. We
      now know that hypoglycemia kills neurons actively rather than by starvation from
      within. Hypoglycemia only causes neuronal death when the EEG becomes flat. This
      usually occurs after glucose levels have fallen below 1 mM (18 mg/dL) for some
      period. At that time abrupt energy failure occurs, the excitatory amino acid
      aspartate is massively released into the limited brain extracellular space and
      floods the excitatory amino acid receptors located on neuronal dendrites. Calcium
      fluxes occur and membrane breaks in the cell lead rapidly to neuronal necrosis.
      Significant neuronal necrosis occurs after 30 min of electrocerebral silence.
      Other neurochemical changes include energy depletion to roughly 25% of control,
      phospholipase and other enzyme activation, tissue alkalosis, and a tendency for
      all cellular redox systems to shift towards oxidation. Hypoglycemia often differs
      from ischemia in its neuropathologic distribution, in that necrosis of the
      dentate gyrus of the hippocampus can occur and a predilection for the superficial
      layers of the cortex is sometimes seen. Cerebellum and brainstem are universally
      spared in hypoglycaemic brain damage. Hypoglycemia constitutes a unique metabolic
      brain insult.

PMID- 15554414
TI  - Cerebral blood flow in acute liver failure: a finding in search of a mechanism.
AB  - In the last few years, several abnormalities of cerebral blood flow (CBF), namely
      loss of cerebral autoregulation, altered reactivity to carbon dioxide, and
      development of cerebral hyperemia, have been described in patients as well as
      experimental models of acute liver failure (ALF) and/or hyperammonemia. The
      development of cerebral hyperemia seems particularly relevant to the pathogenesis
      of brain edema in ALF. In addition to the potential increase of brain blood
      volume causing a rise in intracranial pressure, an increase of CBF could
      facilitate the movement of water across the blood brain barrier in an osmotically
      altered brain. Because maneuvers that abrogate the rise of CBF have been shown to
      prevent or ameliorate brain edema in ALF/hyperammonemia, elucidation of the
      mechanism by which the rise of CBF occurs is important. In the rat after
      portacaval anastomosis receiving an ammonia infusion, the signal resulting in
      cerebral hyperemia arises within the brain once maximal glutamine accumulation
      has occurred in astrocytes. Several mediators potentially involved in the
      development of cerebral hyperemia in ALF are examined in this review, but further
      work is needed to assess the role, if any, of each of them.

PMID- 15554415
TI  - Erythropoietin: novel approaches to neuroprotection in human brain disease.
AB  - With the increased life expectancy in western industrialized countries, the
      incidence and prevalence of brain diseases dramatically increased. Stroke and a
      wide spectrum of neuropsychiatric illnesses such as Alzheimer's disease,
      Parkinson's disease, multiple sclerosis, traumatic head injury, and schizophrenia
      all lead to severe disability. However, targeted effective therapies for
      treatment of these diseases are lacking. Even more frustrating is the fact that
      we do not yet clearly understand the basic mechanisms underlying the disease
      processes in these conditions. We propose a hypothesis of loss of neuronal
      function via a final common deleterious pathway in this clinically very
      heterogeneous disease group. This review presents a novel neuroprotective concept
      for treatment of brain disease: Erythropoietin (EPO). EPO is a natural body-own
      protein hormone that has been used for treatment of anemia for more than a
      decade. The neuroprotective approach using EPO in brain disease represents a
      totally new frontier. The "Gottingen EPO-stroke trial" represents the first
      effective use in man of a neuroprotective therapy in an acute brain disease while
      the experimental EPO therapy to combat cognitive decline in patients with
      schizophrenia will be introduced as an example of a neuroprotective strategy for
      a chronic brain disease.

PMID- 15554416
TI  - Management of patients with fulminant hepatic failure and brain edema.
AB  - Cerebral edema in acute liver failure is associated with a poor prognosis.
      Optimization of cerebral perfusion pressure and blood flow plays a key role in
      contemporary management of these patients. However, understanding of the
      pathophysiology of brain edema is required for optimal patient management. This
      review explains the relationships between cerebral perfusion and edema and
      summarizes therapies that are currently used in patients with acute liver failure
      to prevent and reduce intracranial pressure.

PMID- 15554417
TI  - Hypothermia in acute liver failure.
AB  - The development of encephalopathy in patients with acute liver injury defines the
      occurrence of liver failure. The encephalopathy of acute liver failure is
      characterized by brain edema which manifests clinically as increased intracranial
      pressure. Despite the best available medical therapies a significant proportion
      of patients with acute liver failure die due to brain herniation. The present
      review explores the experimental and clinical data to define the role of
      hypothermia as a treatment modality for increased intracranial pressure in
      patients with acute liver failure.

PMID- 15554418
TI  - MARS--does it stand the test of time?
AB  - Artificial liver support systems have been tested for decades in the management
      of liver failure. Generally, after some promising results published as case
      series, the device either disappears or fails to show significant benefit in
      controlled trials. Recently, the molecular absorbent recycling systems (MARS) or
      extracorporeal albumin dialysis (ECAD) technique appears to have broken this
      trend. Responding to the title one could summarize by saying this technique so
      far has stood the test of time. Data in support of its use in acute liver failure
      (ALF) is still scant and difficult to assess. However, in a well known but not
      very well defined entity of acute on chronic liver failure (AOCLF) the ECAD
      technique has been shown to improve survival compared to a similar randomized
      control group receiving standard supportive therapy. This well tolerated liver
      support system has real potential for widespread application if further well
      designed multicenter clinical trials continue to support its effectiveness. Its
      future lies probably in the management of the moribund hospitalized patient on
      the transplant list awaiting a donor liver.

PMID- 15554419
TI  - Pathophysiology and clinical features of Wilson disease.
AB  - Wilson disease is an autosomal recessive inherited disorder of copper metabolism
      resulting in pathological accumulation of copper in many organs and tissues.
      ATP7B is the gene product of the Wilson disease gene located on chromosome 13 and
      resides in hepatocytes in the trans-Golgi network, transporting copper into the
      secretory pathway for incorporation into apoceruloplasmin and excretion into the
      bile. Mutations of the gene result in impaired trafficking of copper in and
      through the hepatocytes. More than 200 mutations of Wilson disease gene were
      found, the most common ones being H1069Q (in Europe) and R778L (in Asia). Wilson
      disease may present under a variety of clinical conditions, commonly as liver
      and/or neuropsychiatric disease. The pathogenesis of hepatic and neurologic
      Wilson disease is a direct consequence of copper accumulation. Presence of copper
      causes oxidative stress resulting in cell destruction. The diagnosis of Wilson
      disease requires a combination of a variety of clinical symptoms, biochemical
      tests, and detection of gene mutations, which are the basis of a score proposed
      by a group of international experts. Initial treatment for symptomatic patients
      should include a chelating agent (penicillamine or trientine). Treatment of
      presymptomatic patients or maintenance therapy can also be accomplished with
      zinc.

PMID- 15554420
TI  - Increased brain concentrations of endogenous (non-benzodiazepine) GABA-A receptor
      ligands in human hepatic encephalopathy.
AB  - It has been suggested that alterations of GABAergic neurotransmission are
      implicated in the pathophysiology of hepatic encephalopathy (HE). Increased
      concentrations of endogenous benzodiazepines with positive allosteric modulatory
      properties at the GABA-A receptor complex were proposed as a pathophysiological
      mechanism to explain increased GABAergic tone in HE. However, results of
      controlled trials with benzodiazepine receptor antagonists have yielded equivocal
      results and increases in benzodiazepine levels in body fluids of cirrhotic
      patients were suggested to be largely accounted for by previous pharmaceutical
      benzodiazepine intake. In the present study the issue of benzodiazepine receptor
      ligands in brains of cirrhotic patients, and their contribution to alterations of
      GABA-A receptor complex in HE are addressed. "Benzodiazepine-like" ligands were
      present in trace amounts in autopsied brain tissue from control subjects (0.2 +/-
      0.2 ng/g tissue), and from cirrhotic patients not previously exposed to
      benzodiazepine medication (0.8 +/- 0.4 ng/g tissue). In contrast, these ligands
      accumulate in brain extracts from cirrhotic patients previously exposed to
      benzodiazepines by up to 200-fold (161.5 +/- 93.2 DE ng/g tissue). Brain extracts
      from cirrhotic patients increased the binding of the GABA-A receptor agonist
      [3H]muscimol. This increase was minimal with brain extracts from controls (6.8 +/
      2.8%), but was significant with brain extracts from cirrhotic patients without
      (29.4 +/- 2.7%), or with (55.1 +/- 7.6%) previous exposure to benzodiazepines.
      Addition of flumazenil, a selective benzodiazepine receptor antagonist did not
      significantly modify the increase of [3H]muscimol binding by brain extracts from
      patients without prior exposure to benzodiazepines and only partially inhibited
      the increase of [3H]muscimol binding in presence of brain extracts from cirrhotic
      patients previously exposed to benzodiazepines. These findings suggest the
      presence of nonbenzodiazepine substances (possibly neurosteroids) with positive
      allosteric modulatory properties at the GABA-A receptor complex in brain in
      hepatic encephalopathy.

PMID- 15554421
TI  - Characteristics of minimal hepatic encephalopathy.
AB  - The term minimal hepatic encephalopathy refers to the subtle changes in cognitive
      function, electrophysiological parameters, cerebral
      neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and
      fluid homeostasis that can be observed in patients with cirrhosis who have no
      clinical evidence of hepatic encephalopathy. Use of this term emphasizes the fact
      that the entity of hepatic encephalopathy is a single syndrome with
      quantitatively distinct features relating to severity. The absence of clinical
      evidence of hepatic encephalopathy is key to the diagnosis and can only be
      determined by a detailed assessment of the patients' history and a comprehensive
      neurological assessment of consciousness, cognitive, and motor function. The
      neuropsychological features of minimal hepatic encephalopathy point to a disorder
      of executive functioning, particularly selective attention and psychomotor speed,
      but other abnormalities may be observed. Alterations in electrophysiological
      variables have been described; endogenous evoked potentials are, in principle,
      more likely to reflect the presence of minimal hepatic encephalopathy, since they
      reflect cognitive phenomena rather than mere stimulus conduction but the
      specificity of the changes observed is unclear at present. Changes have also been
      described in the execution of diadochokinetic movements and in the capacity to
      discriminate flickering light, both of which may have diagnostic potential. The
      changes observed in cerebral blood flow and metabolism in SPET, PET, and 1H and
      31P MRS studies reflect the pathogenic process that underlies the condition
      rather than providing diagnostic information. Similarly, the morphological brain
      abnormalities identified in this population, including mild brain oedema,
      hyperintensity of the globus pallidus and other subcortical nuclei observed in
      cerebral MR studies, and the central and cortical atrophy observed in neural
      imaging studies, are unlikely to have diagnostic utility. The presence of minimal
      hepatic encephalopathy is not without clinical consequence; it has a detrimental
      effect on health-related quality of life, the ability to perform complex tasks
      such as driving, and on outcome.

PMID- 15554422
TI  - Functional imaging of the brain in patients with liver cirrhosis.
AB  - Brain imaging techniques have provided substantial insight into the
      pathophysiology of hepatic encephalopathy (HE). Magnetic resonance imaging gave
      hint to the fact that there is an increased deposition of manganese especially in
      the basal ganglia. Single photon emission computed tomography (SPECT) and
      positron emission tomography (PET) showed that the preference of the basal
      ganglia might be due to differences in regional cerebral blood flow and an
      additional redistribution of blood flow from the cortex to subcortical regions in
      cirrhotics. PET studies using ammonia as tracer showed that the cerebral
      metabolism of ammonia and the permeability of the blood brain barrier for ammonia
      is increased in cirrhotic patients compared to healthy controls. The regional
      ammonia supply is in accordance with the regional blood flow. In accordance with
      these findings fluorodesoxyglucose-PET-studies of the brain in cirrhotics showed
      characteristic alterations of glucose utilisation in the patients with a relative
      decrease of the glucose utilisation of the cingulate gyrus, the frontomedial,
      frontolateral, and parieto-occipital cortex, while the glucose utilisation of the
      basal ganglia, the hippocampus, and the cerebellum was relatively increased.
      These findings fit well with the clinical characteristics of early stages of HE
      such as deficits in attention, visuo-spatial orientation, visuo-constructive
      abilities, motor speed, and accuracy.

PMID- 15554423
TI  - Methods for diagnosing hepatic encephalopathy in patients with cirrhosis: a
      multidimensional approach.
AB  - There is no "gold standard" for diagnosing hepatic encephalopathy in patients
      with cirrhosis. In consequence, the presence of this condition, unless floridly
      overt, is often missed. As a result, the majority of patients are denied the
      benefits of treatment. There are a number of individual techniques, which access
      different aspects of cerebral function that can be used, singly or in
      combination, to provide diagnostic information in this condition, including
      mental state assessment, psychometric testing, electroencephalography, sensory
      and cognitive evoked potentials, and neuroimaging. These have been variously
      applied to the study of hepatic encephalopathy but fundamental differences in the
      essential aims of the studies, as well as differences in the patient populations
      and the acquisition and analysis of the data, have made comparisons difficult.
      Thus, there is no clear consensus as to the sensitivity, specificity, or validity
      of these tests when used alone or in combination. There are, however, a number of
      additional methods that could be used to analyze the electrophysiological data,
      and a number of alternative evoked potentials that could be measured to provide
      better diagnostic information. In addition, there are a number of techniques,
      such as critical flicker frequency and smooth pursuit eye movements, which have
      not yet been applied systematically in this condition and which may provide
      useful diagnostic information. Clearly the methods for assessing hepatic
      encephalopathy need to be reviewed, newer methods for analyzing the
      electrophysiological data and newer techniques for assessing alternative aspects
      of cerebral function need to be explored for their diagnostic utility. This
      process should aim at developing a multidimensional diagnostic tool.

PMID- 15554425
TI  - Pathophysiology of hepatic encephalopathy: a new look at GABA from the molecular
      standpoint.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with either
      acute or chronic liver failure. More than two decades ago, the role of altered
      GABAergic neurotransmission was proposed following evidence of "increased
      GABAergic tone" in HE. Increased GABAergic tone was based on several
      observations: (i) Similarity of visual evoked response potential patterns between
      rabbits with galactosamine-induced fulminant hepatic failure and animals treated
      with various allosteric agonists of the GABA receptor complex (GRC). (ii)
      Spontaneous activities of isolated Purkinje neurons from rabbits with
      galactosamine-induced fulminant hepatic failure are more depressed by GRC
      modulator compounds compared to normal animals. (iii) Flumazenil, a high
      selective benzodiazepine antagonist at the GRC, ameliorates behavioral symptoms
      and EEG activity in some HE patients. Pathophysiological mechanisms put forward
      to explain increased GABAergic tone in HE include (1) increase in brain GABA
      content due to increased brain GABA uptake through altered permeability of the
      blood brain barrier, (2) alteration of the integrity of constituents of the GRC,
      and (3) increase of endogenous GRC modulators such as benzodiazepines (and more
      recently neurosteroids) with potent agonist properties at the GRC. Studies
      performed subsequently excluded alterations of either GABA content or GRC
      integrity in favor of increased brain concentrations of endogenous agonists.
      While the role of endogenous benzodiazepines remains controversial, the presence
      of neurosteroids with GABA agonist properties affords a plausible explanation for
      increased GABAergic tone in HE.

PMID- 15554424
TI  - Oxidative stress in the pathogenesis of hepatic encephalopathy.
AB  - The pathogenesis of hepatic encephalopathy (HE) remains elusive. While it is
      clear that ammonia is the likely toxin and that astrocytes are the main target of
      its neurotoxicity, precisely how ammonia brings about cellular injury is poorly
      understood. Studies over the past decade have invoked the concept of oxidative
      stress as a pathogenetic mechanism for ammonia neurotoxicity. This review sets
      out the arguments in support of this concept based on evidence derived from human
      observations, animal studies, and cell culture investigations. The consequences
      and potential therapeutic implications of oxidative stress in HE are also
      discussed.

PMID- 15554426
TI  - Blood ammonia levels and hepatic encephalopathy.
AB  - The importance of measurements of the blood ammonia concentration in the
      evaluation of patients with known or suspected hepatic encephalopathy (HE) is
      still disputed in spite of a general acknowledgment that ammonia is important in
      the pathogenesis of the disorder. Several recent studies have suggested that it
      is not necessary to utilize arterial blood when measuring ammonia in the blood.
      Venous blood or a computation of the partial pressure of ammonia gas in blood
      samples may suffice. The value of blood ammonia measurements is limited by the
      fact that this is not the variable that is the most important. Ideally, one would
      like to know how much ammonia enters the brain, not how much is in the blood. The
      blood-brain barrier (BBB) is the critical and poorly understood element in this
      relationship. Although both ammonia in the gas and ionic forms cross the BBB, the
      ease with which this movement occurs is significantly higher in patients with HE.
      In the absence of simple methods to measure the brain ammonia metabolic rate and
      to assess the BBB to ammonia in conjunction with measuring the blood ammonia
      concentration, the variables that would be the most desirable to measure, the use
      of arterial and/or venous blood measurements needs to be coupled with a complete
      understanding of the physiology of cerebral ammonia metabolism.

PMID- 15554427
TI  - Hepatitis C virus infection and the brain.
AB  - While HCV was initially believed to uniformly cause liver inflammation with the
      consequence of liver cirrhosis in most of the infected patients, prospective
      studies have shown a much lower than expected rate of cirrhosis in patients
      infected for more than 20 years. However, a new problem associated with hepatitis
      C virus infection is emerging. This is the development of sometimes disabling
      fatigue. While many other viruses of the flaviviridae cause encephalitis, the
      most closely related virus to HCV in humans, the GB Virus C seems not to be
      associated with fatigue. Thus the mechanism for the development of fatigue in HCV
      infection seems specific for HCV. Delineating the mechanism will be a first step
      to develop treatment option for this currently untreatable impairment.

PMID- 15554429
TI  - Central nervous system involvement in hepatitis C virus infection.
AB  - Hepatic encephalopathy is the most obvious neurological consequence of chronic
      hepatitis C virus (HCV) infection. There are also case reports of HCV-associated
      cerebral vasculitis. This review is concerned with the possibility of an effect
      of HCV on cerebral dysfunction, occurring at an early stage of chronic infection,
      prior to the development of cirrhosis and unrelated to vasculitis. There is
      emerging evidence of mild, but significant neurocognitive impairment in HCV
      infection, which cannot be attributed to substance abuse, coexistent depression,
      or hepatic encephalopathy. In vivo magnetic resonance spectroscopy and
      neurophysiological studies have suggested that a biological mechanism may
      underlie these cognitive findings. The recent detection of HCV genetic sequences
      in postmortem brain tissue raises the intriguing possibility that HCV infection
      of the central nervous system may be related to the reported neuropsychological
      symptoms and cognitive impairment.

PMID- 15554428
TI  - Hepatitis C virus-associated extrahepatic manifestations: a review.
AB  - The hepatitis C virus (HCV) infection is a worldwide disease that is
      characterized by a preferential chronic evolution with mild to severe liver
      disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of
      these complications, HCV is frequently reported to complicate extrahepatic
      manifestations. Among those associated to HCV infection with a high degree of
      certainty, mixed cryoglobulinemia and its complications (skin, neurological,
      renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected
      patients. The other diseases include noncryoglobulinemic systemic vasculitis,
      splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda,
      sicca syndrome, and autoantibodies production. The extrahepatic manifestations
      that share mild-degree certainty of association with HCV infection include B-cell
      non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes
      mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are
      more questionable for their eventual association with HCV and others (pulmonary
      fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's
      corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case
      reports. Howerver, even in cases of tight association, the mechanisms through
      which HCV may promote or induce extrahepatic manifestations remain unclear and
      merit further investigations.

PMID- 15554430
TI  - Microglia.
AB  - Microglia--the macrophage equivalent of the CNS--safeguards and supports neuronal
      functions. Threats to the CNS homeostasis can trigger a rapid transformation of
      these cells from a normally "resting" into alerted and "activated" states.
      Microglia primarily serves the tissue defence and protection when participating
      in mechanisms of innate and adaptive immunity. On the contrary, excessive acute
      or chronic microglial activation can provoke severe neuronal and glial damage by
      carrying or fuelling destructive cascades. Several factors and conditions have
      already been identified that maintain the resting phenotype or organize and
      control the activation process. Cells are thereby able to recognize a dangerous
      signal as well as to sense functional disturbance. Microglial activation is also
      proving a much more variable and adaptive process than previously noticed. Aiming
      at microglia as a therapeutic target, research may focus on intracellular
      pathways that are probably common to activation scenarios as triggered by various
      receptor systems. Certain signalling elements may have key roles in the cytosolic
      integration of sensory inputs and a conversion into programs of executive
      performance. As the integrative aspect of microglial activation becomes
      illuminated hope builds up also on strategies for selective interference with
      harmful outcomes in favour of the--phylogenetically approved--beneficial
      potential of these fascinating cells.

PMID- 15554431
TI  - Serotonin brain circuits with a focus on hepatic encephalopathy.
AB  - Despite enormous strides in our understanding of human disease, the precise
      mechanisms of hepatic encephalopathy (HE), a potential long-term complication of
      liver failure, are still unclear. Brain serotonin, a neurotransmitter with
      widespread distribution in the CNS, plays a role in the regulation of a wide
      range of physiological behaviors and functions. In addition, it has been
      implicated in the pathogenesis of several pathological processes, including HE.
      This work reviews the relationship between brain serotonergic dysfunction and
      hepatic encephalopathy in cirrhotic patients and experimental animals. The
      existing changes in the synthesis, metabolism, storage, and release of neuronal
      serotonin in HE point to a serotonergic synaptic deficit in this condition. Given
      the established role of the brain serotonergic system in the regulation of sleep,
      circadian rhythmicity, and locomotion, selective alterations of this system could
      be an important part of the neurophysiological background responsible for the
      behavioral changes in rats with portacaval anastomosis and may contribute to the
      pathogenesis of HE in cirrhotic patients. The findings that serotoninergic
      turnover is exquisitely and selectively sensitive to the degree of porto-systemic
      shunting and hyperammonemia suggest a role for serotonin in early
      neuropsychiatric symptoms of HE. Pharmacological manipulation of the brain
      serotonergic system may be beneficial in the prevention and treatment of HE in
      cirrhotic patients.

PMID- 15554432
TI  - Fatigue complicating chronic liver disease.
AB  - Fatigue is common and can be profound in patients with chronic liver diseases,
      such as primary biliary cirrhosis (PBC) and chronic hepatitis C. The pathogenesis
      of fatigue in such patients is unknown; it may be related to infection with the
      hepatitis C virus or the pathophysiology of cholestasis in PBC, to a
      psychological reaction to knowledge of the diagnosis, or to the presence of
      chronic liver disease. A major problem in evaluating a treatment for fatigue in a
      randomized controlled trial is the inherent subjectivity of fatigue and the lack
      of a satisfactory objective quantitative primary efficacy endpoint. Experimental
      studies in rats and male athletes have implicated the serotonin neurotransmitter
      system in fatigue of central origin. Administration of the 5-HT3 serotonin
      receptor subtype antagonist, ondansetron, has been associated with substantial
      sustained clinical ameliorations of profound fatigue in at least some patients
      with chronic liver disease.

PMID- 15554434
TI  - The CEO as a communicator.

PMID- 15554433
TI  - Changes in brain size in hepatic encephalopathy: a coregistered MRI study.
AB  - Magnetic resonance imaging (MRI) coregistration techniques can be used to track
      changes in brain volume. We aimed to determine whether treatment in chronic liver
      disease altered brain size. The study group comprised nine patients with
      cirrhosis (7 Child's grade B and 2 Child's grade C). Six had minimal and three
      had overt hepatic encephalopathy on clinical, psychometric, and
      electrophysiological testing. Cerebral MRI was performed in seven patients before
      and 6 weeks after starting lactulose. A further two patients underwent
      transjugular intrahepatic portosystemic stent shunting with MRI performed before
      and 24 h afterwards. One patient had a further scan 3 months after TIPSS. Brain
      size was measured using a semiautomated contour/thresholding technique.
      Measurable changes were found after treatment intervention, but there was no
      correlation with severity of encephalopathy (West Haven criteria) or liver
      dysfunction (Child's score). Three patients improved on lactulose, the brain size
      decreased with an increase in ventricular volume. Two patients deteriorated; the
      brain size increased with a concomitant decrease in ventricular volume. Two
      stable patients had small changes, one with an increase in brain size and a
      decrease in ventricular volume and the other showing the converse. Following
      TIPSS, there was an increase in brain size in both patients, evident within 24 h
      in one patient and at 3 months in the other. Coregistered MRI demonstrates easily
      detectable changes in brain size following treatment intervention. Our results
      support the hypothesis that low-grade brain swelling is present, even in minimal
      hepatic encephalopathy.

PMID- 15554435
TI  - Virtua Health's CEO, Richard P. Miller, works well with doctors. Major issues
      include professional liability crisis, charity care, taxation of physician
      practices.

PMID- 15554436
TI  - The New Jersey and national experience with influenza in 2003-2004 and specific
      new recommendations for 2004-2005.

PMID- 15554437
TI  - An unusual presentation of toxic shock syndrome.

PMID- 15554438
TI  - Financing New Jersey's hospitals.

PMID- 15554439
TI  - Child and adolescent mental health; June 2004.

PMID- 15554440
TI  - Child and adolescent mental health; June 2004.

PMID- 15554441
TI  - CPC; July-August 2004.

PMID- 15554442
TI  - CPC; July-August 2004.

PMID- 15554443
TI  - MDA has demonstrated their never ending reactive rather than proactive
      leadership.

PMID- 15554444
TI  - Annual session takes long preparation.

PMID- 15554445
TI  - A shared spirit.

PMID- 15554446
TI  - Core restoration for crown preparation.
AB  - This article will review the relevant literature fom 1991-2003, a period of time
      when adhesive resin luting materials became available and luting crowns with zinc
      phosphate cements decreased. The review wtill look at the principles suggesting
      when a core should be placed, what core materials function best, preparation
      design with a core, luting material choice with a core, and results of clinical
      trials. Amalgam cores are regarded as the strongest material, best able to
      withstand adverse stress and restore teeth having the greatest loss of tooth
      structure. Composite resins, whether chemically cured or light cured, reinforced
      or not, appear best capable of core restorationfor moderately broken down teeth.
      Glass ionomer materials are considered too weak to withstand stress as a core
      material, but are recommended as a base material tofill in undercuts and improve
      the accuracy of impression and fit of a crown.

PMID- 15554447
TI  - Take a dental benefits decision maker to lunch.

PMID- 15554448
TI  - What's a dentist to do?

PMID- 15554449
TI  - Gordon's syndrome: a case report.
AB  - Authors describe a case of syndrome of Gordon, a rare genetic disease
      characterized by hypertension, hyperkalemia and normal glomerular filtration
      rate. The potential causes of disease are discussed and literature data are
      reviewed.

PMID- 15554450
TI  - Comparative study of the antihypertensive activity of Marrubium vulgare and of
      the dihydropyridine calcium antagonist amlodipine in spontaneously hypertensive
      rat.
AB  - Water extract of Marrubium vulgare is widely used as antihypertensive treatment
      in folk medicine. We have compared the effect of 10-week-long treatment with
      amlodipine or Marrubium water extract on systolic blood pressure (SBP),
      cardiovascular remodeling and vascular relaxation in spontaneously hypertensive
      rats (SHR). Both treatments produced similar decrease in SBP. Amlodipine
      treatment reduced left ventricle, aortic and mesenteric artery weight. Marrubium
      treatment had a significant antihypertrophic effect in aorta only. Relaxation to
      acetylcholine (ACh) of mesenteric artery was improved by Marrubium but not by
      amlodipine treatment. These results demonstrate that, in addition to its
      antihypertensive effect, Marrubium water extract improved the impaired
      endothelial function in SHR.

PMID- 15554451
TI  - Effect of sodium on vasoconstriction and angiotensin II type 1 receptor mRNA
      expression in cold-induced hypertensive rats.
AB  - Angiotensin II and sodium play an important pathogenetic role in several models
      of hypertension. Now, we investigated the effects of sodium on vasoconstriction
      and angiotensin II type 1 (AT1) and type 2 (AT2) receptor mRNA expression in
      aortic vessels from cold-induced hypertensive rats. Wistar rats on low sodium and
      high sodium diet were exposed to cold-stress for 8 weeks. The effects of
      angiotensin II infusion on mean arterial blood pressure were investigated in
      these rats. In addition, angiotensin II induced contraction was measured using
      aortic rings. Expression of AT1 receptor mRNA and AT2 receptor mRNA was assessed
      in aortic vessels by reverse transcription polymerase chain reaction. After
      infusion of angiotensin II mean arterial blood pressure in cold-induced
      hypertensive rats on high sodium diet was significantly higher compared to cold
      induced hypertensive rats on low sodium diet (p < 0.05). Angiotensin II-induced
      contraction of aortic rings was significantly higher in cold-induced hypertensive
      rats on high sodium diet compared to cold-induced hypertensive rats on low sodium
      diet (2.39 +/- 0.03 g vs. 2.21 +/- 0.04 g, n = 12, p < 0.01). Angiotensin AT1
      receptor mRNA was significantly higher in cold-induced hypertensive rats on high
      sodium diet compared to cold-induced hypertensive rats on low sodium diet (p <
      0.05). It is concluded that in this nongenetic, nonsurgical animal model of cold
      induced hypertension increased vasoconstriction and increased AT1 receptor mRNA
      expression in aortic vessels are dependent on sodium intake.

PMID- 15554452
TI  - Cardiac mechanical dysfunction induced by ischemia-reperfusion in perfused heart
      isolated from stroke-prone spontaneously hypertensive rats.
AB  - We investigated the difference in mechanical function after ischemia and
      reperfusion between Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats
      (SHR) or stroke-prone SHR (SHRSP) using the isolated working heart model, in
      order to examine postischemic mechanical dysfunction in the severely
      hypertrophied heart. Systolic blood pressure of SHRSP was higher than that of SHR
      and WKY, and the left ventricular wall in SHRSP was thicker than in WKY.
      Mechanical dysfunction of the heart during reperfusion following ischemia (11
      min) in SHRSP was severer than that in SHR and WKY, and recovery of the cardiac
      energy charge potential (ECP) level in SHRSP was lower than that in SHR and WKY.
      Twenty-five, 12 and 11 min-ischemia in WKY, SHR and SHRSP, respectively, caused a
      similar level of cardiac mechanical damage. Also, the ECP levels were almost
      equivalent among them at the end of 20 min reperfusion following each time of
      ischemia. Under each ischemic condition, a Ca2+-channel blocker, diltiazem, and
      an adenosine potentiator, dilazep, produced a beneficial effect on the post
      ischemic dysfunction in SHR and WKY. However, neither cardioprotective drug led
      to recovery of the mechanical dysfunction of the heart during reperfusion
      following ischemia in SHRSP. Thus, the severely hypertrophied heart such as that
      in SHRSP was more susceptible to cardiac reperfusion dysfunction, than the
      moderately hypertrophied heart such as that in SHR. These results suggest that
      the cardioprotective effects of drugs may be deteriorated in severe hypertrophied
      hearts.

PMID- 15554453
TI  - Nitric oxide donation lowers blood pressure in adrenocorticotrophic hormone
      induced hypertensive rats.
AB  - Adrenocorticotrophic hormone (ACTH) elevates systolic blood pressure (SBP) and
      lowers plasma reactive nitrogen intermediates in rats. We assessed the ability of
      NO donation from isosorbide dinitrate (ISDN) to prevent or reverse the
      hypertension caused by ACTH. In the prevention study, male Sprague Dawley rats
      were treated with ACTH (0.2 mg/kg/day) or saline control for 8 days, with either
      concurrent ISDN (100 mg/kg/day) via the drinking water or water alone. Animals
      receiving ISDN via the drinking water were provided with nitrate-free water for 8
      hours every day. In the reversal study ISDN (100 mg/kg) or vehicle was given as a
      single oral dose on day 8. SBP was measured daily by the indirect tail-cuff
      method in conscious, restrained rats. ACTH caused a significant increase in SBP
      compared with saline (P < 0.0015). In the prevention study, chronic
      administration of ISDN (100 mg/kg/day) did not affect the SBP in either group. In
      the reversal study, ISDN significantly lowered SBP in ACTH-treated rats at 1 and
      2.5 hours (132 +/- 3 mmHg (1 h) and 131 +/- 2 mmHg (2.5 h) versus 143 +/- 3 mmHg
      (0 h), P < 0.002), but not to control levels. It had no effect in control (saline
      treated) rats. In conclusion, the lowering of SBP by NO donation is consistent
      with the notion that ACTH-induced hypertension involves an impaired
      bioavailability or action of NO in vivo.

PMID- 15554454
TI  - Contractile responses of aortae from WKY and SHR to vasoconstrictors.
AB  - Aortae taken from spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats
      aged 4, 8 and 16 weeks were prepared as rings and used to measure the effects of
      five vasoconstrictors. The endothelium was removed in order to measure
      selectively the contractile responses induced by potassium chloride (KCl),
      phenylephrine (PHE), angiotensin-II (Ang II), endothelin-1 (ET-1) and human
      urotensin-II (U-II). These responses were assumed to derive from the activation
      of specific receptors (namely alpha1, AT1, ETA and UT-II) or from depolarization
      of the smooth muscle fibers by KCl. Specific antagonists prazosin, losartan, BQ
      123 and [Orn8]-UII were used at various concentrations for a pharmacological
      characterization of these latter receptor systems. The primary purpose of the
      study was to explore mechanisms or factors that may intervene in the development
      and maintenance of high blood pressure in SHR. Results indicate that isolated
      aortae of SHR and WKY contain contractile sites (receptors) whose pharmacological
      profiles (pEC50 for agonists, pA2 for antagonists) are very similar to those of
      other biological systems and should be considered as typical for the alpha1, AT1,
      ETA and UT-II receptor types. Aortae taken from SHR 4 (non hypertensive), 8 and
      16 weeks old (hypertensive) responded to the vasoconstrictors with reduced
      maximal contractions compared to those of age-matched WKY. These unexpected
      reduced responses of aortae, observed with the five vasoconstrictors, may be
      attributed to a non specific lesions. Maximal contraction of aortae from SHR
      increased from 4 to 16 weeks for KCI, PHE and U-II, decreased for Ang II, and
      remained stable for ET-1. There was also an age-dependent increase of maximal
      contraction induced by U-II in WKY. It is suggested that aortae from SHR undergo
      early remodelling that leads to reduced contractility in vitro and possibly to
      vessel rigidity in vivo. The factors involved in this process appear to be of
      genetic origin since they are present before hypertension: they may contribute to
      modify aortic compliance and perhaps vascular resistance in hypertensive animals
      and thus being the cause and not the consequence of high blood pressure.

PMID- 15554455
TI  - Hemodynamic effects of the nitric oxide donor DETA/NO in mice.
AB  - (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate
      (DETA/NO) is a recently synthesized member of NO-releasing, polyamine
      zwitterions, the so-called NONOates, that spontaneously liberate NO in aqueous
      solutions. The aim of this study was to determine the hemodynamic effects of
      DETA/ NO in normotensive and hypertensive mice. Male Swiss Outbred mice were
      implanted with TA11PA-C20 blood pressure devices (Data Sciences International,
      USA). After recovery (7-10 days), blood pressure was monitored for 10 days while
      mice were receiving saline (0.1 ml/20 g/day, s.c.). Mice were then treated every
      four hours for 1 day with either DETA/NO 60 mg/kg i.p. or the inactive
      metabolite, diethylenetriamine 38 mg/kg (molar equivalent) i.p. After a 2 week
      wash-out period, mice were treated with adrenocorticotrophic hormone (ACTH: 500
      microg/kg/day, s.c.) for 10 days and re-challenged with DETA/NO or
      diethylenetriamine. Results were expressed as mean +/- SEM. After 10 days of
      saline treatment, baseline systolic and diastolic blood pressure (BP) were
      similar for animals subsequently receiving DETA/NO or the amine (123 +/- 1/95 +/-
      3 and 124 +/- 1/92 +/- 0.2 mmHg) respectively. DETA/NO induced a profound fall in
      BP [Systolic: 74 +/- 4 mmHg (-40 +/- 3%); Diastolic: 46 +/- 4 mmHg (-52 +/- 4%)]
      and an increase in heart rate [729 +/- 33 bpm (32 +/- 2%)] within the first 80
      minutes. Diethylenetriamine had no effect. ACTH treatment increased BP in both
      groups (137 +/- 16/108 +/- 12 and 161 +/- 1/142 +/- 1 mmHg) respectively. DETA/
      NO induced a profound fall in blood pressure [Systolic: 92 +/- 11 mmHg (-32 +/-
      7%); Diastolic: 68 +/- 10 mmHg (-35 +/- 10%)] and an increase in heart rate [613
      +/- 36 bpm (18 +/- 6%)] within the first 80 minutes. Again diethylenetriamine had
      no significant effect. There was no significant effect on body weight with any
      treatment. Thus DETA/NO has potent blood pressure lowering effects in both
      normotensive and hypertensive mice.

PMID- 15554456
TI  - Neurohumoral mechanisms involved in the hypertensive response elicited by
      bilateral carotid occlusion in conscious intact or chronically sympathectomized
      rats.
AB  - Bilateral carotid occlusion (BCO) increases the sympathetic drive to the
      circulatory system in conscious intact rats, producing a hypertensive response
      characterized by two components, i.e., an initial peak followed by a sustained
      response of lower intensity. The neurohumoral mechanisms involved in the
      hypertensive response to BCO were evaluated in conscious intact (INTACT) or
      chronic guanethidine sympathectomized (SYMPX) rats. To accomplish this, the
      receptor antagonists, prazosin for alpha1-adrenergic receptor, losartan for AT1
      angiotensin II receptor and [d(CH2)5Tyr(Me)AVP] for vascular V1 vasopressin
      receptor were used. A saline control group was studied as well. Conscious rats
      were equipped with cuffs around the common carotid arteries plus arterial and
      venous catheters. The results indicate that the sympathetic nervous system is the
      main mechanism controlling the basal arterial pressure in conscious INTACT rats,
      whereas in chronically SYMPX rats the renin-angiotensin system plays this role.
      In INTACT rats prazosin abolished the initial peak and blunted the sustained
      hypertensive response due to BCO, while the other antagonists exhibited no
      effect. SYMPX rats did not present the initial peak but displayed an enhanced
      sustained response, which was blunted by prazosin or the vasopressin antagonist.
      In conclusion, activation of the sympathetic drive is responsible for both the
      initial peak and the sustained hypertensive response due to BCO in conscious
      INTACT rats. On the other hand, vasopressin acting in concert with the
      sympathetic nervous system, plays a key role in the potentiation of the sustained
      hypertensive response due to BCO in conscious chronically SYMPX rats.

PMID- 15554457
TI  - Insulin resistance, body mass index, waist circumference are independent risk
      factor for high blood pressure.
AB  - OBJECTIVES: The purpose of the present study was to investigate the relationships
      between blood pressure (BP), insulin resistance as determined by a homeostasis
      model (HOMA-IR), and body fat distribution. METHODS: Anthropometric indices of
      adiposity, metabolic variables (fasting serum insulin and a homeostasis model
      assessment [HOMA] index of insulin sensitivity), BP and several cardiovascular
      risk factors were measured during a cross sectional survey of 53477 apparently
      healthy Korean subjects who requested a health status check. Hypertension was
      defined as a systolic BP > or = 140 mmHg or a diastolic BP > or = 90 mmHg and we
      excluded the subjects taking BP-lowering medication. RESULTS: Systolic and
      diastolic blood pressure (SBP, DBP) were positively and significantly associated
      with age, body mass index, waist circumference, and waist/hip ratio. In addition,
      SBP and DBP were positively associated with fasting serum insulin levels and the
      HOMA index. By multiple regression analysis age, waist circumference, body mass
      index, HOMA index and female sex were independently associated with either
      increased SBP or DBP. When the population is divided into quintiles according to
      insulin resistance (measured by HOMA analysis) prevalence of hypertension in the
      second, third, fourth and fifth quintiles compared to subjects in the first
      quintile are 1.004(95% CI 0.875-1.152, p = 0.957), 1.200(95% CI 1.052-1.369, p =
      0.007), 1.312(95% CI 1.151-1.494 p < 0.001 ), and 1.603(95% CI 1.408-1.825 p <
      0.001). In addition age, sex, body mass index and waist circumference were found
      to be significantly associated with hypertension. CONCLUSION: Our results showed
      that insulin resistance, body mass index and waist circumference are independent
      risk factors of a high BP in Koreans.

PMID- 15554458
TI  - The initial stage of left ventricular hypertrophy in spontaneously hypertensive
      rats is manifested by a decrease in the QRS amplitude/left ventricular mass
      ratio.
AB  - In this study we tested the hypothesis of the relative voltage deficit, i.e. the
      discrepancy between increased left ventricular mass (LVM) and QRS amplitudes, in
      an experimental model of spontaneously hypertensive rats (SHR) during the period
      of a moderate increase in blood pressure. To address this issue we recorded
      orthogonal electrocardiograms of male SHR at the age of 12 and 20 weeks. During
      this period the systolic blood pressure (sBP) increased from 165 +/- 3 mmHg to
      195 +/- 1 mmHg (p < 0.001). Age and sex matched WKY rats were used as control
      groups. The sBP values in WKY normotensive control groups were within normal
      limits (122 +/- 8 mmHg and 130 +/- 4mmHg, respectively). The maximum QRS spatial
      vector magnitude (QRSmax) was calculated from X, Y, Z amplitudes of the
      orthogonal electrocardiograms. The animals were sacrificed and the left
      ventricular mass was weight. The specific potential of myocardium (SP) was
      calculated as a ratio of QRSmax to LVM. The LVM in SHR (0.86 +/- 0.05 g and 1.05
      +/- 0.07 g, respectively) was significantly higher as compared to WKY (0.65 +/-
      0.07 g and 0.70 +/- 0.02 g), and the increase of LVM closely correlated with the
      sBP increase. On the other hand, QRSmax in SHR did not follow either the increase
      of sBP, or LVM. The QRSmax values in SHR did not differ from those of WKY at the
      age of 12 weeks (0.59 +/- 0.14 mV compared to 0.46 +/- 0.05 mV), and they were
      even lower in SHR at the age of 20 weeks (0.74 +/- 0.08 mV compared to 0.44 +/-
      0.05 mV, p < 0.001). The values of SP, quantifying the relative voltage deficit,
      were significantly lower in SHR as compared to the WKY control. The values
      decreased significantly in SHR with increasing age, sBP and LVM, i.e., with the
      progression of hypertrophic remodeling of the left ventricle. The results of this
      study support the hypothesis of the relative voltage deficit in LVH. These
      results are consistent with the finding of a high number of false negative ECG
      results in clinical ECG diagnostics of LVH, and could contribute to an
      understanding of the diagnostic importance of the false negative ECG results,
      their re-evaluation and utilization for clinical diagnosis and prognosis.

PMID- 15554459
TI  - Activity of angiotensin-converting enzyme after treatment with L-arginine in
      renovascular hypertension.
AB  - The renin-angiotensin system plays a role in the pathophysiology of renovascular
      hypertension. In addition, some studies have demonstrated a beneficial effect of
      L-arginine (L-Arg), the precursor of nitric oxide (NO), in this model of
      hypertension. This study was designed to investigate the effects of L-Arg on
      cardiovascular parameters and on the activity of the angiotensin-converting
      enzyme (ACE), after 14 days of renovascular hypertension. The experiments were
      performed on conscious male Wistar rats. Two-kidney, one-clip renovascular
      hypertension (2KIC) was initiated in rats by clipping the left renal artery
      during 14 days, while control rats were sham-operated. One group was submitted to
      a similar procedure and treated with L-Arg (10 mg/ml; average intake of
      300mg/day) from the 7th to the 14th day after surgery, whereas the respective
      control group received water instead. At the end of the treatment period, the
      mean arterial pressure (MAP) was measured in conscious animals. The rats were
      sacrificed and the ACE activity was assayed in heart and kidneys, using Hip-His
      Leu as substrate. In a separate group, the heart was removed, the left ventricle
      (LV) was weighed and the LV/body weight ratios (LV/BW) were determined. We
      observed significant differences in MAP between the L-Arg-treated and untreated
      groups (129 +/- 7 vs. 168 +/- 6 mmHg; P< 0.01). The cardiac hypertrophy described
      for this model of hypertension was attenuated in the 2K1C-L-Arg-treated group
      (14th day, wet LV/BW: 2K1C-L-Arg = 1.88 +/- 0.1; 2K1C = 2.20 +/- 0.1 mg/g; P <
      0.05). L-Arg administration caused an important decrease in cardiac ACE activity
      (2K1C-L-Arg: 118 +/- 15; 2K1C: 266 +/- 34 micromol/min/mg; P < 0.01). L-Arg also
      decreased the ACE activity in the clipped kidney by 47% (P < 0.01), but not in
      the nonclipped kidney. These data suggest that increased NO formation and reduced
      angiotensin II formation are involved in the anthihypertensive effect of orally
      administered L-arginine.

PMID- 15554460
TI  - Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with
      therapeutic efficacy of benazepril on essential hypertension in Chinese.
AB  - BACKGROUND: There is considerable variability in individual response to
      antihypertensive agents. The reason for this is not known, but may be related to
      individual genetic variability. This study examined whether the therapeutic
      efficacy of benazepril on essential hypertension is modified by beta2 adrenergic
      receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. METHODS AND RESULTS: We
      conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi
      and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic
      blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were
      measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele
      frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In
      Yuexi family-based association test (FBAT) revealed that the G16 allele was
      associated with a greater DBP decrease in response to a 15-day benazepril
      treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant
      inheritance model. A similar trend was observed in Huoqiu Chinese, but the
      magnitudes of effects were smaller and did not reach statistical significance.
      The FBAT results were further confirmed by using a generalized estimating
      equation model. CONCLUSION: Our family-based study provided the first evidence
      that ADRB2 R16G polymorphism may play an important role in DBP response to
      benazepril treatment, although the magnitude of the effect appears to be modified
      by other risk factors such as plasma lipid and glucose profiles.

PMID- 15554461
TI  - Hypnotherapeutic ego strengthening with male South African coronary artery bypass
      patients.
AB  - Morbidity (i.e., elevated anxiety and depression) is a common feature of coronary
      artery bypass surgery (CABS) patients, pre- and postoperatively. Since
      hypnotherapy can possibly reduce morbidity in CABS patients, the aim of this
      study was to determine the feasibility of hypnotherapeutic ego strengthening
      (HES) to facilitate patient coping with concomitant anxiety and depression. Fifty
      patients were randomly assigned to a non-intervention control group (n = 25) and
      an experimental group (n = 25) and exposed to a pre- and postoperative HES
      intervention. Anxiety and depression were assessed with the Beck Depression
      Inventory and Profile of Mood States, administered preoperatively, at discharge,
      and at 6-week follow-up. Findings confirmed large practical reductions of anxiety
      and depression in the experimental group and were maintained at follow-up, while
      a trend towards increased depression levels occurred in the control group.
      Although not generalizable, results suggest broadened applications of
      hypnotherapy with patients in cardiac centers.

PMID- 15554462
TI  - Stressors associated with dyspnea in childhood: patients' insights and a case
      report.
AB  - OBJECTIVE: To highlight the concept that stress can be associated with dyspnea in
      children. METHODS: A chart review identified 22 patients (age range, 9-17 years)
      referred to a pediatric pulmonologist, who were offered instruction in self
      hypnosis for treatment of dyspnea that persisted despite medical therapy.
      Patients were offered the opportunity to use hypnosis to gain insight into the
      causes of their dyspnea. RESULTS: The dyspnea resolved in 18 of the 22 patients
      within 1 month of instruction in self-hypnosis for relaxation and symptom
      reduction. Eight of the 22 patients (age range, 11-16 years) chose to use
      hypnosis for insight. Using automatic word processing, they explained that their
      dyspnea was associated with stressful situations, or that it reduced the chances
      of having to experience an uncomfortable situation. For example, a girl with
      dyspnea resulting from vocal cord dysfunction realized during hypnosis that she
      developed her symptom in order to prevent herself from talking about information
      that might cause discomfort were it disclosed. As soon as the patient decided
      that she could trust herself to handle the information appropriately, her symptom
      resolved. CONCLUSIONS: Dyspnea may provide patients with a way of expressing
      their reactions to perceived or anticipated stress. Thus, stress reduction
      interventions may prove very helpful in resolving this symptom. However, in some
      cases gaining an insight into the potential cause of the dyspnea may increase the
      effectiveness of therapy.

PMID- 15554463
TI  - A continuum of hypnotherapeutic interactions: from formal hypnosis to hypnotic
      conversation.
AB  - Hypnotherapeutic interactions can be mapped on a continuum from formal hypnosis
      to hypnotic conversation. Unlike the structured forms of formal hypnosis,
      hypnotic conversation relies upon utilizing the client's responses, both verbal
      and non-verbal, to facilitate therapeutic process. In this paper, we illustrate
      this continuum with a series of anecdotal clinical examples starting with formal
      hypnosis and moving incrementally towards hypnotic conversation. Finally, we
      offer an example similar in appearance to formal hypnosis, but now described in
      the context of hypnotic conversation. We are neither putting forth a theory nor
      offering a new perspective for those who research hypnosis as a phenomenon.
      Rather, these ideas and metaphors serve to broaden the framework of what
      constitutes hypnotic interaction so as to evoke new opportunities for increasing
      therapeutic efficiency and efficacy.

PMID- 15554464
TI  - Enhancing suggestibility: the effects of compliance vs. imagery.

PMID- 15554465
TI  - Nurses are heroes.

PMID- 15554466
TI  - Unique issues in pediatric spinal cord injury.
AB  - Spinal cord injuries are devastating events, and they are particularly tragic
      when they affect children or adolescents who have barely had an opportunity to
      experience life. Of the approximately 10,000 individuals who sustain spinal cord
      injury each year in the United States, 3% to 5% occur in individuals younger than
      15 years of age and approximately 20% occur in those younger than 20 years of age
      (Nobunaga, Go, & Karunas, 1999). Because of the growth and development inherent
      in children and adolescents and the unique manifestations and complications
      associated with spinal cord injuries, management must be developmentally based
      and directed to the individual's special needs (Vogel, 1997). The many unique
      facets of pediatric spinal cord injuries are addressed in this article. They
      clearly delineate the need for care that is responsive to the dynamic changes
      that occur with growth and development. The multidisciplinary team, combined with
      a focus on family-centered care, is essential in pediatric spinal cord injuries.

PMID- 15554467
TI  - Psoriatic arthritis.
AB  - Psoriatic arthritis is an inflammatory arthritis associated with the skin
      disorder psoriasis. The exact etiology of psoriatic arthritis is unknown,
      although more than 40% of people with the cutaneous disease of psoriasis are
      estimated to also have joint involvement. This article presents an overview of
      psoriatic arthritis, including the origin, genetic influence, and immunologic
      factors involved in its evolution. The clinical features of psoriatic arthritis
      are also reviewed in this article, and a discussion of the diagnosis and
      treatment is included.

PMID- 15554468
TI  - Height change and bone mineral density: revisited.
AB  - PURPOSE: To evaluate the relationship between height change, osteoporosis risk
      factors, and bone mineral density. SAMPLE: Secondary data collected on 168
      healthy women, ages 50 to 65 years, who had a dual energy x-ray absorptiometry
      screening of the hip and spine to determine bone mineral density. METHOD: A
      quantitative secondary analysis of data that replicated in part a study by Hunt
      (1996). FINDINGS: The relationships between height change, osteoporosis risk
      factors, and bone mineral density were not significant for this group of healthy
      postmenopausal women. However, these women did not meet daily minimum
      requirements for dietary calcium intake and daily exercise. IMPLICATIONS: The
      good news is that healthy women ages 50 to 65 years still have time to engage in
      osteoporosis preventing behaviors to prevent bone loss and eventual height loss.
      The use of measured height change, as an indicator for osteoporosis risk, is a
      cost-saving tool and should be considered as one component of a comprehensive
      osteoporosis health appraisal incorporating daily calcium intake and exercise.
      Further research, with more precise measurement of height, needs to be done to
      evaluate the relationship between height change, osteoporosis risk factors, and
      bone mineral density.

PMID- 15554469
TI  - Spirituality in nursing: what are the issues?
AB  - This article describes the author's attempt to highlight the problem areas
      associated with providing spiritual care for patients. The focus of this work is
      to discuss the following areas of interest: What is spirituality? The issue of
      spirituality in nursing. The impact of spirituality for the patient. The
      relevance or irrelevance of religion. The concept of serenity as a goal for
      nursing practice. The author provides examples, specifically regarding older
      people, explaining why spiritual care of patients is decidedly problematic in the
      British healthcare system and provides suggestions as to how to reintegrate this
      essential part of caregiving back into daily practice.

PMID- 15554470
TI  - Massage therapy for the orthopaedic patient: a review.
AB  - The effectiveness of massage therapy for the orthopaedic patient has not been
      documented; thus, a review of the published literature was warranted. A
      considerable proportion of the population experience orthopaedic problems, and
      many use massage therapy. A review and analysis of the literature between January
      1973 and June 2003 yielded tentative results. It appears that massage therapy may
      be effective for orthopaedic patients with low back problems and potentially
      beneficial for patients with other orthopaedic problems. Massage therapy appears
      to be safe, to have high patient satisfaction, and to reduce pain and
      dysfunction.

PMID- 15554471
TI  - The use of guided imagery to manage pain in an elderly orthopaedic population.
AB  - BACKGROUND: The management of postoperative pain in elderly orthopaedic patients
      is critical for advancing patient outcomes and improving the use of healthcare
      resources. Adequate pain control without adverse side effects, such as confusion
      and sedation, is crucial to promote comfort and participation in rehabilitation
      therapies among all patients but particularly among elderly joint replacement
      patients. Without adequate pain control, physical therapy is delayed and the risk
      of complications increases. One area of investigation that holds promise for
      improved treatment outcomes involves the use of complementary therapies, such as
      guided imagery. PURPOSE: The purpose of this pilot study was to test the effects
      of a guided imagery intervention in the older adult patient who has undergone
      joint replacement surgery. SAMPLE AND METHODS: This pilot study used a two-group
      experimental repeated measures design. A sample of 13 patients, age 55 years and
      older, were recruited. The control group received usual care and a music audio
      tape. The experimental group received usual care and a guided imagery audio tape
      intervention. FINDINGS AND DISCUSSION: Trends in this pilot study demonstrated
      positive outcomes for pain relief, decreased anxiety, and decreased length of
      stay. Complementary therapy holds the promise of increasing positive outcomes.
      Further research is needed to validate these findings with a larger postoperative
      sample and in other populations as well. CLINICAL IMPLICATIONS: There is a
      critical need to incorporate the use of guided imagery and other complementary
      therapies into all nursing curricula. Nurses must develop expertise and be ready
      and able to act as patient educators and advocates in the use of these
      interventions in programs of care and institutional policy.

PMID- 15554472
TI  - The titanium rib: creating room to grow.

PMID- 15554473
TI  - Lead uptake and the effects of EDTA on lead-tissue concentrations in the desert
      species mesquite (Prosopis spp.).
AB  - Experimental results have shown that the desert plant species mesquite (Prosopis
      spp.) is capable of accumulating high levels of lead in the roots, translocating
      it to the aerial portion of the plant. One-week-old mesquite seedlings were
      treated for 7 d in a hydroponic culture using a modified Hoagland solution. Six
      treatments were used; three treatments contained only Pb [as Pb(NO3)2] at 25-, 50
      , and 75-mg L(-1) levels and three treatments contained the same levels of Pb,
      but with equimolar concentrations of disodium ethylenediamine tetraacetic acid
      (EDTA). Our results showed that the plants exposed to 25-, 50-, and 75-mg Pb L(
      1) treatments without EDTA concentrated in stems 524, 3726, and 1417 mg kg(-1),
      respectively. However, the plants treated with Pb-EDTA concentrated in stems 480
      , 607-, and 1247-mg Pb kg(-1) for the 25-, 50-, and 75-mg Pb L(-1) treatments,
      respectively. Results for the roots followed a similar trend; without EDTA the Pb
      levels ranged from 16,055, 89,935, and 63,396 for the 25-, 50-, and 75-mg Pb L(
      1) treatments, respectively, and with EDTA these levels were 9,562, 49,902, and
      39,181 mg kg(-1) for the three treatments. However, the addition of EDTA
      increased lead movement to the leaves. The levels of Pb without EDTA were 20, 35,
      and 51 mg kg(-1) for the 25-, 50-, and 75-mg Pb L(-1) levels, respectively.
      Treatments with EDTA showed uptake levels of 105, 124, and 313 for the 25-, 50-,
      and 75-mg Pb L(-1) treatments. Further, the percent Pb in dry leaf tissues for
      all EDTA treatments were greater than 0.1%. However, only the 25-mg Pb L(-1)
      treatment was greater than 0.1%, compared to 0.04 and 0.08% for the 50- and 75-mg
      Pb L(-1) treatments, respectively. Preliminary transmission and scanning electron
      microscopy corroborate the presence of lead.

PMID- 15554474
TI  - Temperature and pH effects on plant uptake of benzotriazoles by sunflowers in
      hydroponic culture.
AB  - This article describes a systematic approach to understanding the effect of
      environmental variables on plant uptake (phyto-uptake) of organic contaminants.
      Uptake (and possibly phytotransformation) of xenobiotics is a complex process
      that may differ from nutrient uptake. A specific group of xenobiotics
      (benzotriazoles) were studied using sunflowers grown hydroponically with changes
      of environmental conditions including solution volume, temperature, pH, and
      mixing. The response of plants to these stimuli was evaluated and compared using
      physiological changes (biomass production and water uptake) and estimated uptake
      rates (influx into plants), which define the uptake characteristics for the
      xenobiotic. Stirring of the hydroponic solution had a significant impact on plant
      growth and water uptake. Plants were healthier, probably because of a combination
      of factors such as improved aeration and increase in temperature. Uptake and
      possibly phytotransformation of benzotriazoles was increased accordingly.
      Experiments at different temperatures allowed us to estimate an activation energy
      for the reaction leading to triazole disappearance from the solution. The
      estimated activation energy was 43 kJ/mol, which indicates that the uptake
      process is kinetically limited. Culturing plants in triazole-amended hydroponic
      solutions at different pH values did not strongly affect the biomass production,
      water uptake, and benzotriazole uptake characteristics. The sunflowers showed an
      unexpected capacity to buffer the solution pH.

PMID- 15554475
TI  - Bacterial community evaluation during establishment of tall fescue (Festuca
      arundinacea) in soil contaminated with pyrene.
AB  - A greenhouse study was conducted to monitor microbial community dynamics related
      to contaminant concentration and plant growth during the phytoremediation of
      pyrene. Soil microbial communities in both bulk and rhizosphere soils were
      assessed using a polymerase chain reaction--denaturing gradient gel
      electrophoresis (PCR-DGGE). However, no correlation between pyrene concentration
      and bacterial community shifts was observed. Even though plants significantly
      enhanced pyrene degradation (undetectable after 91 d for planted treatments
      compared with 82 mg/kg for unplanted treatments after 147 d with initial
      concentration of 758 mg/kg), biodegradation may have been accomplished by the pre
      existing microbial community. It is also possible that the method was unable to
      pick up subtle community shifts, considering that the carbon source from pyrene
      was only 3.7% of the existing soil organic matter. This research suggests that
      plants significantly enhance degradation and mineralization of pyrene in soil,
      although there was no conclusive evidence supporting any specific bacterial
      activity responsible for this enhancement.

PMID- 15554476
TI  - Determination of the relative uptake of ground vs. surface water by Populus
      deltoides during phytoremediation.
AB  - The use of plants to remediate polluted groundwater is becoming an attractive
      alternative to more expensive traditional techniques. In order to adequately
      assess the effectiveness of the phytoremediation treatment, a clear understanding
      of water-use habits by the selected plant species is essential. We examined the
      relative uptake of surface water (i.e., precipitation) vs. groundwater by mature
      Populus deltoides by applying irrigation water at a rate equivalent to a 5-cm
      rain event. We used stable isotopes of hydrogen (D) and oxygen (18O) to identify
      groundwater and surface water (irrigation water) in the xylem sap water.
      Pretreatment isotopic ratios of both deuterium and 18O, ranked from heaviest to
      lightest, were irrigation water > groundwater > xylem sap. The discrepancy in
      preirrigation isotopic signatures between groundwater and xylem sap suggests that
      in the absence of a surface source of water (i.e., between rain events) there is
      an unknown amount of water being extracted from sources other than groundwater
      (i.e., soil surface water). We examined changes in volumetric soil water content
      (%), total hourly sapflux rates, and trichloroethene (TCE) concentrations.
      Following the irrigation treatment, volumetric soil water increased by 86% and
      sapflux increased by as much as 61%. Isotopic signatures of the xylem sap became
      substantially heavier following irrigation, suggesting that the applied
      irrigation water was quickly taken up by the plants. TCE concentrations in the
      xylem sap were diluted by an average of 21% following irrigation; however,
      dilution was low relative to the increase in sapflux. Our results show that water
      use by Populus deltoides is variable. Hence, studies addressing phytoremediation
      effectiveness must account for the relative proportion of surface vs. groundwater
      uptake.

PMID- 15554477
TI  - Plant-assisted degradation of phenanthrene as assessed by solid-phase
      microextraction (SPME).
AB  - The soil bacterium Sphingomonas yanoikuyae was isolated from a petroleum
      contaminated soil and grown on mineral salts agar overlaid with the polycyclic
      aromatic hydrocarbon phenanthrene. The effect of white mustard, Sinapis alba, on
      phenanthrene degradation by S. yanoikuyae in artificially contaminated Redi-earth
      sand was examined. Solid-phase-microextraction (SPME) gas chromatography-flame
      ionization detection (GC-FID) was used to quantify the concentration of
      phenanthrene in the gas phase of Magenta jars containing S. alba and S.
      yanoikuyae, each alone and with no additions. Gas chromatography-mass
      spectrometry (GC-MS) of Soxhlet extracts was used to determine the concentration
      of phenanthrene remaining in Redi-earth-sand. The gas phase concentration of
      phenanthrene in nonsterile Redi-earth-sand decreased by 99.7% in treatments with
      S. alba plus S. yanoikuyae, by 98.6% with S. alba, by 96.7% with S. yanoikuyae,
      and by 95.8% with no additions. Under gnotobiotic conditions, the gas phase
      concentration of phenanthrene in Redi-earth-sand decreased by 94% in treatments
      with S. alba plus S. yanoikuyae, by 77% with S. yanoikuyae, by 26% with S. alba,
      and 0% with no additions. The concentration of phenanthrene in Redi-earth-sand
      under gnotobiotic conditions decreased in treatments with S. alba plus S.
      yanoikuyae by 88%, by 67% with S. yanoikuyae, by 13% with S. alba, and 0% with no
      additions as measured in Soxhlet extracts. These results suggest that SPME-GC can
      be used to rapidly assess the potential of plants and microorganisms to reduce
      the level of unaged polyaromatic hydrocarbons such as phenanthrene in soil. This
      method provided results that were consistent with the more costly Soxhlet
      extraction method and was less time consuming.

PMID- 15554478
TI  - Cadmium and copper uptake and translocation in five willow (Salix L.) species.
AB  - The efficacy for phytoremediation of five willow species was tested by
      experimental copper and cadmium uptake in a greenhouse hydroponic system. Five
      treatments included two concentrations (5 and 25 microM for each metal) and a
      control. Metal concentrations in solution as well as solution uptake were
      monitored. Metal resistance was assessed through effects on the dry weight of
      roots and shoots. The willow species tested were generally resistant of increased
      Cu and Cd content. Metal accumulation was found in all plant organs of all
      species. Growth and transpiration were not decreased by 5 microM of copper and 25
      microM of cadmium in the solution for most species. 25 microM copper caused
      injury and reduced the dry weight for all species after 21 d. Salix nigra was
      highly resistant of both Cu and Cd and accumulated more metals than other
      species. Future field study should be conducted to confirm the findings and
      feasibility of the phytoremediation technology using those species.

PMID- 15554479
TI  - Genomics and the family physician: realizing the potential.

PMID- 15554480
TI  - Rhinosinusitis: what is the desired outcome?

PMID- 15554481
TI  - Nontreponemal test titer printout for patients with syphilis.

PMID- 15554482
TI  - Use of diuretics to treat hypertension in diabetic persons.

PMID- 15554483
TI  - Interventions for impetigo.

PMID- 15554484
TI  - Donepezil in the treatment of vascular dementia.

PMID- 15554485
TI  - NSAIDs vs. opiates for pain in acute renal colic.

PMID- 15554486
TI  - Acute bacterial rhinosinusitis in adults: part I. Evaluation.
AB  - Acute rhinosinusitis is one of the most common conditions that physicians treat
      in ambulatory practice. Although often caused by viruses, it sometimes is caused
      by bacteria, a condition that is called acute bacterial rhinosinusitis. The signs
      and symptoms of acute bacterial rhinosinusitis and prolonged viral upper
      respiratory infection are similar, which makes accurate clinical diagnosis
      difficult. Because two thirds of patients with acute bacterial rhinosinusitis
      improve without antibiotic treatment and most patients with viral upper
      respiratory infection improve within seven d antibiotic therapy should be
      reserved for use in patients who have had symptoms for more than seven days and
      meet clinical criteria. Four signs and symptoms are the most helpful in
      predicting acute bacterial rhinosinusitis: purulent nasal discharge, maxillary
      tooth or facial pain (especially unilateral), unilateral maxillary sinus
      tenderness, and worsening symptoms after initial improvement. Sinus radiography
      and ultrasonography are not recommended in the diagnosis of uncomplicated acute
      bacterial rhinosinusitis, although computed tomography has a role in the care of
      patients with recurrent or chronic symptoms.

PMID- 15554487
TI  - Acute bacterial rhinosinusitis in adults: part II. Treatment.
AB  - Although most cases of acute rhinosinusitis are caused by viruses, acute
      bacterial rhinosinusitis is a fairly common complication. Even though most
      patients with acute rhinosinusitis recover promptly without it, antibiotic
      therapy should be considered in patients with prolonged or more severe symptoms.
      To avoid the emergence and spread of antibiotic-resistant bacteria, narrow
      spectrum antibiotics such as amoxicillin should be used for 10 to 14 days. In
      patients with mild disease who have beta-lactam allergy,
      trimethoprim/sulfamethoxazole or doxycycline are options. Second-line antibiotics
      should be considered if the patient has moderate disease, recent antibiotic use
      (past six weeks), or no response to treatment within 72 hours. Amoxicillin
      clavulanate potassium and fluoroquinolones have the best coverage for Haemophilus
      influenzae and Streptococcus pneumoniae. In patients with beta-lactam
      hypersensitivity who have moderate disease, a fluoroquinolone should be
      prescribed. The evidence supporting the use of ancillary treatments is limited.
      Decongestants often are recommended, and there is some evidence to support their
      use, although topical decongestants should not be used for more than three days
      to avoid rebound congestion. Topical ipratropium and the sedating antihistamines
      have anticholinergic effects that maybe beneficial, but there are no clinical
      studies supporting this possibility. Nasal irrigation with hypertonic and normal
      saline has been beneficial in chronic sinusitis and has no serious adverse
      effects. Nasal corticosteroids also may be beneficial in treating chronic
      sinusitis. Mist, zinc salt lozenges, echinacea extract, and vitamin C have no
      proven benefit in the treatment of acute bacterial rhinosinusitis.

PMID- 15554488
TI  - Information from your family doctor. Sinus infections.

PMID- 15554489
TI  - Tympanometry.
AB  - Tympanometry provides useful quantitative information about the presence of fluid
      in the middle ear, mobility of the middle ear system, and ear canal volume. Its
      use has been recommended in conjunction with more qualitative information (e.g.,
      history, appearance, and mobility of the tympanic membrane) in the evaluation of
      otitis media with effusion and to a lesser extent in acute otitis media. It also
      can provide useful information about the patency of tympanostomy tubes.
      Tympanometry is not reliable in infants younger than seven months because of the
      highly compliant ear canals of infants. Tympanogram tracings are classified as
      type A (normal), type B (flat, clearly abnormal), and type C (indicating a
      significantly negative pressure in the middle ear, possibly indicative of
      pathology). According to the Agency for Healthcare Research and Quality
      guidelines on otitis media with effusion, the positive predictive value of an
      abnormal (flat, type B) tympanogram is between 49 and 99 percent. A type C curve
      may be useful when correlated with other findings, but by itself it is an
      imprecise estimate of middle ear pressure and does not have high sensitivity or
      specificity for middle ear disorders.

PMID- 15554490
TI  - Childhood bullying: implications for physicians.
AB  - Childhood bullying has potentially serious implications for bullies and their
      targets. Bullying involves a pattern of repeated aggression, a deliberate intent
      to harm or disturb a victim despite the victim's apparent distress, and a real or
      perceived imbalance of power. Bullying can lead to serious academic, social,
      emotional, and legal problems. Studies of successful antibullying programs
      suggest that a comprehensive approach in schools can change student behaviors and
      attitudes, and increase adults' willingness to intervene. Efforts to prevent
      bullying must address individual, familial, and community risk factors, as well
      as promote an understanding of the severity of the problem. Parents, teachers,
      and health care professionals must become more adept at identifying possible
      victims and bullies. Physicians have important roles in identifying at-risk
      patients, screening for psychiatric comorbidities, counseling families about the
      problem, and advocating for bullying prevention in their communities.

PMID- 15554491
TI  - Information from your family doctor. Bullying.

PMID- 15554492
TI  - Common dietary supplements for weight loss.
AB  - Over-the-counter dietary supplements to treat obesity appeal to many patients who
      desire a "magic bullet" for weight loss. Asking overweight patients about their
      use of weight-loss supplements and understanding the evidence for the efficacy,
      safety, and quality of these supplements are critical when counseling patients
      regarding weight loss. A schema for whether physicians should recommend, caution,
      or discourage use of a particular weight-loss supplement is presented in this
      article. More than 50 individual dietary supplements and more than 125 commercial
      combination products are available for weight loss. Currently, no weight-loss
      supplements meet criteria for recommended use. Although evidence of modest weight
      loss secondary to ephedra-caffeine ingestion exists, potentially serious adverse
      effects have led the U.S. Food and Drug Administration to ban the sale of these
      products. Chromium is a popular weight-loss supplement, but its efficacy and long
      term safety are uncertain. Guar gum and chitosan appear to be ineffective;
      therefore, use of these products should be discouraged. Because of insufficient
      or conflicting evidence regarding the efficacy of conjugated linoleic acid,
      ginseng, glucomannan, green tea, hydroxycitric acid, L-carnitine, psyllium,
      pyruvate, and St. John's wort in weight loss, physicians should caution patients
      about the use of these supplements and closely monitor those who choose to use
      these products.

PMID- 15554493
TI  - Screening and behavioral counseling interventions in primary care to reduce
      alcohol misuse.

PMID- 15554494
TI  - Screening mammography in women 40 to 49 years of age.

PMID- 15554495
TI  - The value of tongue laceration in the diagnosis of blackouts.

PMID- 15554496
TI  - Completing and signing the death certificate.

PMID- 15554497
TI  - Emerging human protozoan infections in the temperate European climate.
AB  - There has been a resurgence of interest in medical protozoology in the last
      twenty years or so mainly as a result of the recognition of HIV infection and the
      opportunistic protozoan infections associated with it. Many new species of
      microsporidia have been recognised as parasites causing human disease and several
      rare infections, such as isosporiasis, have become more commonly recognised, even
      in temperate climates. Some of the infections seen in temperate regions have
      arrived through foreign travel (tourism, work or immigration), sometimes
      exacerbated by immunosuppression (due to HIV, organ transplantation or
      malignancy). Importation of food from around the world and climate change (global
      warming) may also be contributing to the increase in previously rare protozoan
      infections now being seen in temperate regions. This article reviews the current
      status of these new and re-emerging human protozoan infections in temperate,
      rather than tropical locations.

PMID- 15554498
TI  - Histopathological aspects of Dengue-2 virus infected mice tissues and
      complementary virus isolation.
AB  - The difficulty in studying dengue virus (DENV) infection in humans and in
      developing a virus vaccine is the absence of a suitable animal model which
      develops the full spectra of the Dengue haemorrhagic fever (DHF) and Dengue shock
      syndrome (DSS). Despite the fact that viruses have been found in various animal
      tissues, we isolated DENV from tissues of adult BALB/c mice, inoculated with DENV
      serotype 2 (DENV-2) obtained from human serum. Viruses were ultrastructurally
      identified and immunolocalized by immunofluorescence techniques in C6/36 mosquito
      cell cultures, inoculated with tissues (liver, lung, kidney and cerebellum)
      macerate supernatant from mice, 48 h post-infection (p.i.). These organs,
      collected at the same stage of infection, were examined histologically. The
      histopathological analysis revealed focal alterations in all tissues examined.
      Liver contained focal ballooned hepatocytes, but without modifying the average
      diameter of the majority of hepatocytes. Sinusoidal lumen was significantly
      diminished at this stage but portal and centrolobular veins became congested.
      Lungs exhibited hemorrhagic foci in the alveolar space, vascular congestion and
      focal alveolitis. Cerebellar tissue showed rare foci of neuronal compactation
      (Purkinje cells) and perivascular oedema. In kidneys it was observed an increase
      in glomerular volume with augmented endocapillary and mesangial cellularity, with
      reactivity to anti-IgM in all glomeruli of infected mice. In conclusion, DENV-2
      was found in all tissues examined early in the evolution of infection. Presence
      of viruses in tissues has mainly led to hemodynamic alterations with generalized
      vascular congestion and increased permeability, and mast cell recruitment in
      lungs. The latter could participate in the vascular modifications in tissues.

PMID- 15554499
TI  - Ultrastructural and morphometric studies of normal rat hepatocytes.
AB  - To investigate the arrangement of organelles in normal rat liver hepatocytes, we
      examined liver tissues by electron microscopy. We also analyzed hepatocyte
      organelles by morphometry using the NIH image software. The smooth ER area
      appears as a network of branching tubules and contains many glycogen rosettes.
      The rough ER area presents lamellar plates and contains free polyribosomes. The
      Golgi complex area comprises the parallel smooth surface of associated vesicles
      and contains secretory granules, lysosomes and a few glycogens. Ratio of the
      cross-sectional area of hepatocytes shows the smooth ER area (60 +/- SD 1.5%),
      the rough ER area (35 +/- SD 1.4%) and the Golgi complex area (4 +/- SD 1.7%) of
      the total cytoplasm. The rough ER shows a dendrite pattern in a hepatocyte. Many
      mitochondria are spread between the smooth ER and the rough ER area. The smooth
      ER directly communicates with the rough ER, the Golgi complex cisternae at a
      forming face and the nuclear envelope. Anastomosing tubules with polyribosomes
      between the smooth ER and rough ER, between smooth ER and the nuclear envelope
      frequently. These results provide a basics at the cellular level for better
      understanding the experimentally induced changes and for improving the
      pathological hepatic diagnosis.

PMID- 15554500
TI  - Intraepithelial alterations in the guinea pig lateral prostate at different ages
      after estradiol treatment.
AB  - The prostate is an accessory gland of the mammal reproductive system with great
      volume and high functional importance. Many works infer that, in addition to the
      androgenic ones, the estrogen can be associated with benign prostatic hyperplasia
      and prostatic cancer, but no conclusive evidence exists on the role of estrogen
      in normal prostatic and neoplastic tissue. The objective of this work was to
      evaluate the effects of chronic administration of estradiol benzoate on the
      lateral prostate of guinea pigs in the pre-pubescent, pubescent, post-pubescent
      and adult phases, with emphasis on the modifications provoked by this hormone on
      the glandular epithelium. The analyses of the estradiol-treated and control
      groups were investigated using histological procedures and transmission electron
      microscopy. The histopathological analysis of the lateral prostate in the treated
      group revealed areas where epithelial dysplasia was observed, assuming at some
      places a pattern of epithelial stratification characteristic of prostatic
      intraepithelial neoplasia. After ultrastructural analysis, the following were
      observed: enlargement of the internal membranes, heterogeneity in the cellular
      types, hypertrophy of the basal cells and apparent decrease of cytoplasmic
      organelles in some cells of the prostatic intraepithelial neoplasia. Still, a
      loss of cellular polarity was observed, along with nuclei of various forms, sizes
      and heights--as well as irregular chromatin distribution patterns. Such
      alterations were found mainly in pubescent, post-pubescent and adult animals
      subject to the chronic administration of estradiol. These findings reinforce the
      already existent data in understanding the role of estrogen in the etiology of
      prostatic diseases.

PMID- 15554501
TI  - Effects of Azadirachta indica and Melia azedarach (Meliaceae) extracts from
      leaves on Trypanosoma cruzi growth and ultrastructure.
AB  - The chloroformic extracts from dried fresh leaves ofAzadirachta indica A. Juss.
      and Melia azedarach L. (Meliaceae) showed marked inhibitory activity on
      epimastigotes growth of Trypanosoma cruzi, evidenced by 96-wells microtiter plate
      bioassay and radioactive thymidine incorporation experiment. Each chloroformic
      extract was separated using silica gel and alumina column. In transmission
      electron microscopy the bioactive chromatographic fractions caused
      ultrastructural changes in epimastigotes such as vacuolization probably induced
      by degeneration of the kinetoplast-mitochondrion complex, organelle degeneration,
      and cell division disruption. In spectral analysis these bioactive fractions
      seemed to be composed mainly of fatty acid mixtures.

PMID- 15554502
TI  - The ultrastructure of the nasal polyps in patients with and without cystic
      fibrosis.
AB  - Nasal polyps are commonly associated with cystic fibrosis (CF) and also with
      idiopathic allergies, asthma, and aspirin intolerance. The pathogenesis of nasal
      polyp formation is controversial. The present study investigates the
      ultrastructure of thirteen nasal polyps surgically removed from seven CF patients
      and six non-CF (NCF) patients with allergic diseases, asthma, and aspirin
      intolerance. All nasal polyps showed focal edema, hyperplasia, atrophy, or
      squamous metaplasia of the epithelium. The lamina propria was moderately
      populated with small blood vessels and mucous glands and showed focal
      accumulation of inflammatory cells. The CF nasal polyps, however, revealed
      several specific characteristics: 1) minimal damage to the surface epithelium, 2)
      presence of a mucus blanket lining the apical epithelium, 3) occasional
      intracytoplasmic lumens, 4) continuous and fenestrated type capillaries, 5)
      numerous degranulated mast cells, 6) many plasma cells, often with atypical
      morphology and intracisternal Russell bodies, and 7) a smaller number of
      eosinophils as compared to the NCF nasal polyps. The results indicate significant
      differences between CF and NCF nasal polyps and support the multifactorial
      pathways theory of nasal polyp formation.

PMID- 15554503
TI  - Ultrastructural pathology of neuronal membranes in the oedematous human cerebral
      cortex.
AB  - Surgical biopsies of frontal, parietal and temporal regions of thirty two
      patients with clinical diagnosis of congenital hydrocephalus, brain trauma,
      tumours, and vascular anomalies were examined with the transmission electron
      microscope. The main goal was to study the submicroscopic alterations of
      somatodendritic, axonal, and synaptic plasma membranes, cytomembranes, and the
      cytoskeleton. In both, moderate and severe oedema, fragmentation of plasma
      membrane, enlargement and focal necrosis of rough endoplasmic cisterns and
      nuclear envelope, detachment of membrane-bound ribosomes and reduction of
      polysome were observed. The degenerated myelinated axons exhibited
      discontinuities of the axolemma, disorganisation of multiple myelin lamellae,
      myelin sheath vacuolization, and formation of myelin ovoids. In severe oedema,
      synaptic disassembly was frequently found characterized by separate pre- and
      postsynaptic endings and loss of perisynaptic glial ensheathment. Fragmented and
      intact microtubules and actin-like filaments also were distinguished. The
      alterations of plasma membranes and cytomembranes are related with the anoxic
      ischaemic conditions of brain parenchyma. The role of free radical and lipid
      peroxidation, disturbed energy metabolism, altered metabolic cascades,
      excitotoxicity, protein aggregation, and presence of extracellular oedema fluid
      is discussed in relation with the derangement of neuronal membranes.

PMID- 15554504
TI  - Transmission electron microscopy of cortical dendritic spines in the human
      oedematous cerebral cortex.
AB  - The cortical biopsies of 31 patients with clinical diagnosis of congenital
      hydrocephalus, vascular anomalies, brain tumours and brain trauma were examined
      with the transmission electron microscope. A variety of swollen spine shapes were
      found: mushroom shaped, filopodic, lanceolated spines, and megaspines. The spines
      appeared axonless or making asymmetric synaptic contacts with swollen presynaptic
      axons. They exhibited a disrupted actin-like network, dilated endoplasmic
      reticulum profiles, oedematous clear or dense mitochondria, and clusters of free
      ribosomes. Some spines contained a hypertrophic cytoskeleton. The spine apparatus
      appeared generally swollen with clear and dilated cisterns. In severe brain
      trauma and tumours some spine apparatus appeared disorganised or atrophic. In
      complicated brain trauma with subdural haematoma or hygroma some degenerated
      spines displayed a high electron density. The ultrastructural findings suggest
      that alterations of the spines are responsible for the neurological symptoms
      exhibited by some patients, which imply a disturbance of cortical nerve circuits.
      The presence of axonless spines is symptomatic of a loss of nerve connectivity,
      and are expected to have a significant input on neurological and mental
      functions.

PMID- 15554505
TI  - Mossy fibers in granule cell areas of the rat dorsal cochlear nucleus from
      intrinsic and extrinsic origin innervate unipolar brush cell glomeruli.
AB  - Non tonotopic transmission between cochlear nuclei and other auditory and non
      auditory nuclei in the brain is probably due to large axonal terminals (mossy
      fibers) innervating granule cell areas of cochlear nuclei. The origin of mossy
      fibers in the dorsal cochlear nucleus (DCN) is multiple, from other auditory or
      non-auditory nuclei but possibly also from intrinsic neurons. The present
      ultrastructural immunocytochemical study reports for the first time the presence
      of anterograde-labeled mossy fibers in the DCN of the rat after injection of the
      neural tracer WGA-HRP into 3 different nuclei. Labeled mossy fibers were seen in
      9.0% of mossy fibers detected after tracer injection into the ipsilateral
      anteroventral cochlear nucleus, in 7.3% of mossy fibers after contralateral
      collicular injection, and 13.2% after contralateral cochlear nucleus injection.
      Most (over 95%) mossy fibers contained round vesicles, both large and small, and
      were likely excitatory terminals, but few showed flat-pleomorphic vesicles that
      contained the inhibitory neurotransmitters GABA and glycine. Most of the
      anterograde-labeled ipsilateral mossy fibers containing small round synaptic
      vesicles, are probably derived from multipolar neurons within the ipsilateral
      anteroventral cochlear nucleus. After injections into the contralateral inferior
      colliculus, it was not possible to distinguish putative descending collicular
      mossy fibers from intrinsic mossy fibers. The latter would suggest the presence
      of an amplification pathway within the DCN, from collateral axons of pyramidal or
      stellate cells of the ipsilateral ventral cochlear nucleus to form glomeruli with
      granule-unipolar brush cells. After injection into the contralateral cochlear
      nucleus, it was not possible to distinguish between commissural mossy fibers and
      those derived from ipsilateral recurrent axon-terminals of commissural neurons
      within the DCN or the ventral cochlear nucleus. Despite this limitation, the
      present observations show that extrinsic or intrinsic mossy fibers reach granule
      cell areas in layers 2 and 3 of the DCN and form glomeruli of large or small
      dimension (1.5-4 microm) with unipolar brush and granule cells. These mossy
      fibers probably carry a fast excitatory non-tonotopic input which may influence
      the electrical response of granule cell areas.

PMID- 15554506
TI  - Postovulatory ageing induces structural changes in the mouse zona pellucida.
AB  - The structure of the zona pellucida (ZP) was analyzed in mouse oocytes collected
      soon after ovulation and in others retrieved 20 h after. The conventional methods
      for electron microscopy and the alcoholic PTA staining procedure which
      preferentially contrasts lysine-rich proteins were employed. The ZP of aged
      oocytes showed several structural changes which were particularly observed after
      using the PTA procedure. In 82.14% of the aged oocytes the ZP appeared clearly
      composed of two different regions: an inner dense and an outer of low density.
      The ZP showed a fibrillar banded structure with a parallel arrangement of
      fibrillar threads in both the outer and inner regions. The in vitro fertilization
      analysis showed that only 16.85% of the aged gametes attained the two cell embryo
      stage in comparision to 66.93% shown by the freshly ovulated eggs. The non
      fertilized oocytes showed that no sperm penetration through the ZP occurred.

PMID- 15554507
TI  - [Hospitals between present and future].
AB  - What role will hospitals play in the future of the healthcare system, and how
      this role will be changing? Hospitals of the future will confront difficult
      challanges: new kinds of disease, rapidly evolving medical technologies, aging of
      the population and evolving budget restrictions. All features that make it
      difficult to foresee the hospital of the future. The aim of this paper is to
      analyze the different challanges that hospital have to face in a modern scenario
      of evolution of public health services.

PMID- 15554508
TI  - [The emergency refund system in Lazio region: features and problems].
AB  - In Lazio region, in which Rome is located and 5,300,000 inhabitants live, an
      Information System has been started since 1999 to collect personal and clinical
      data of the admissions to Emergency Departments. The present work describes the
      fundamental aspects of the Region refund system for the emergency services made
      by the Emergency Departments. The article shows both the features of the
      information flow, on which the financial evaluation is based, and the fundamental
      steps of the regional deliberations for the years 2000 and 2001. We introduce the
      refund evaluations by 13 local health authorities (ASL) constituting the regional
      health service, for the years 2000-2001, and we point out the major problems
      related to calculation procedures. The total amount of emergency admissions in
      the region is 1,973,930 (year 2000) and 2,188,885 (year 2001). The evaluated
      charge for the region is 145,569,340 Euro (year 2000), and 170,004,718 Euro (year
      2001).

PMID- 15554509
TI  - [The outpatient care in the Latium region (Italy) in 2001].
AB  - The Region of Latium has been operating an Outpatient Care Information System
      (SIAS) since 1997 to monitor the supply of outpatient care in a territory with a
      population of over five million. The present work has the aim of describing the
      outpatient care in the region, in terms of number of facilities involved by
      category (public and private, operating in the regional public health system) and
      volume of procedures rendered to residents in 2001. Of the 971 outpatient
      facilities operating in hospitals and elsewhere--37% state managed and 67%
      private--distributed in a non-uniform manner throughout the region, the majority
      is concentrated in the city of Rome, which by itself accounts for 49% of its
      total amount of facilities, and in a lesser measure in the other provincial
      capitals (Viterbo, Rieti, Frosinone, Latina). In 2001, 71 million procedures were
      performed, comprising 17 million prescriptions, for an economic value of over 400
      million Euros. The three specialties of greatest use were Lab Analysis, Physical
      Therapy and Rehabilitation, and Radiology, making up 88% of the total outpatient
      procedures performed within the precinct of the regional health service, in
      respective measures of 57%, 27%, and 4%. It is noted that the public facilities
      are prevalently polyspecialistic while a great number of private facilities are
      monospecialistic and perform procedures almost exclusively (96%) in the three
      specialties of greatest use. The other specialties which receive notable use are
      Cardiology, Eye Care, Orthopedics and Neurology. In general, the greater the
      number of facilities there are in either the public or private sector, the
      greater the level of activity in terms of procedures performed, with the
      exception of the area of Physical Therapy and Rehabilitation where the
      correlation is inversely proportioned; in fact, for this specialty the public
      facilities, which are represented in a much greater number throughout the region,
      supply only 7% of the volume of activity.

PMID- 15554510
TI  - [The health services epidemiology in health agency: the initiatives, the
      activities, the structures. Introduction to the subject].
AB  - The subject which has been developed within the Workshop "the health services
      Epidemiology in health Agency: the initiatives, the activities, the structures.
      Direct and indirect evidences", held in Rome, in November 15th, 2001, is
      introduced and updated. After a historical excursus, the topical interest in the
      health services epidemiology, which has now assumed the aspect of a real,
      independent discipline, and the reasons for its development, are analysed. As an
      independent discipline, its typical methodology and function have to be
      recognised. The methodology is characterised by the wide use of qualitative
      methods, by the importance assigned to the secondary epidemiologic research (i.e.
      systematic reviews and meta-analysis) and by the particular interest devoted to
      evaluation rather than investigative surveys. The function is aimed at improving
      people's health by means of health care services and, as a practical consequence,
      useful to the former one, at improving the quality of health care services
      themselves.

PMID- 15554511
TI  - [Osteoporosis: problems and considerations of economical nature].
AB  - In 1991 WHO classified osteoporosis as a major social disease, on the basis of
      its high prevalence, expected to rise in the future, its physical and
      psychological consequences and its economical costs for both the society and the
      individual. In the past, costs, especially the undirected and intangible ones,
      have been largely underestimated, due to their complex quantification. A more
      accurate and a deeper evaluation of the pathology and its economical burden on
      National Health Services will lead to a better planning of prevention strategies.

PMID- 15554512
TI  - [The no. 210/92 law: an analysis of the applications for damages caused by
      vaccine's administrations and transfusions].
AB  - Practices related to vaccines and transfusions aren't free of risk as regards
      complications and undesired effects. The no. 210/92 law lays down payments to
      people who are damaged in consequence of the administration of obligatory
      vaccines, transfusions and haemoderivatives. Our study valued law's sticking,
      analysing applications for payment sent in by damaged people to some ASL of Lazio
      and Abruzzo, in the period 1992-2000.

PMID- 15554513
TI  - [Risk management in health care systems: the new legislative orientations in
      medical civil responsibility].
AB  - The recent radical change in the relationships between physicians and patients
      has increased the frequency of malpractice. Consequently, on one hand, many
      physicians got used to avoiding any possible risk of denunciation by applying the
      so called "defensive medicine", while on the other hand, the insurance companies
      raised the prices of their premiums for policies concerning civil responsibility
      of health operators. In order to avoid this "vicious circle", some health
      structures created Units for the Risk Management related to malpractice, while
      others took advantage of the collaboration of Associations for Patients' Rights
      to create database about the most frequent medical mistakes. The need for a
      legislative change has been accepted by the Parliament which expects with the
      proposal n.108 (approved in spring 2002 by the Commission for Hygiene and Health
      of the Senate) to attribute the civil responsibility of the physicians to the
      hospitals (both private and public) for which they work, to constitute a Register
      of experts and to accelerate the legal disputes. The problem is complex and still
      to be solved, but it seems that time for a strong intervention in order to
      improve the situation has to come.

PMID- 15554514
TI  - [Evaluating hospital appropriateness with different tools: administrative data
      versus analytic review].
AB  - PRUO, a modified version of AEP, is a widely used clinical-based tool to evaluate
      hospital appropriateness in Italy. We developed the APPRO method for assessing
      organizational appropriateness using administrative data. APPRO estimates the
      amount of inappropriate hospitalisation, giving consideration to severity of
      illness through APR-DRG classification system. The aims of the study were to:
      measure the agreement between evaluators using PRUO; investigate the relation
      between APR-DRG severity subgroups and PRUO assessment; asses the validity of
      APPRO method comparing its performance to PRUO results. We selected 361 hospital
      episodes assigned to DRG 39 ("lens procedures with or without vitrectomy") and
      242 hospital episodes assigned to DRG 183 ("miscellaneous of digestive disorders,
      age > 17") from three hospitals in 2000. Clinical records were independently
      evaluated by two pairs of physicians using PRUO. Proportions of inappropriate
      episodes by hospital and DRG were also estimated through APPRO using data from
      Lazio regional hospital information system. The agreement between the two pairs
      of evaluators was high (k=0.93; p<0.0001). We observed no statistically
      significant association between APR-DRG severity subgroups and inappropriate
      hospitalisation found by PRUO. APPRO underestimates rates of inappropriate
      hospitalisation compared to PRUO. It depends on the different characteristics of
      the tools and particularly on the caution of APPRO in performing the evaluation
      using routine data.

PMID- 15554515
TI  - Clonal spread of Acinetobacter baumannii in a general intensive care unit.
AB  - The epidemiological characterization of multiply resistant Acinetobacter
      baumannii isolates from a six-bed Intensive Care Unit (ICU) is described.
      Investigations for A. baumannii were performed in three subsequent surveillance
      studies. In the first study, surveillance cultures were taken from patients,
      health care personnel and the environment; in the second study surveillance
      cultures were taken at 0, 4, and 7 days from all patients admitted consecutively
      to the ward; and in the third study surveillance cultures were taken from
      patients, health care personnel and the environment. During the first study all
      four hospitalized patients were found to harbour A. baumannii. Hand cultures did
      not grow any A. baumannii when staff entered the ward from home, but 7 positive
      health care workers were identified out of 25 samples taken during work, and two
      cultures of environmental specimens grew A. baumannii. During the second study, 4
      of 86 (4.6%) patients resulted colonized with A. baumannii. In the third
      epidemiological study, no A. baumannii was cultured from either patients, health
      care personnel or the environment. All isolates recovered from various patients
      or sources produced conserved macrorestriction Pulsed-Field Gel Electrophoresis
      (PFGE) patterns and showed the same antibiotic resistance; therefore, they can be
      considered indistinguishable. The same antibiotic resistance and macrorestriction
      patterns were observed in previously isolated A. baumannii strains in the ward
      during May 1997, suggesting the persistence of a single A. baumannii in the ICU.
      The present study confirms that molecular typing is an essential tool in the
      epidemiology and control of nosocomial infections, showing here the persistence
      of a single A. baumannii clone in the ICU. The origin of this strain remains
      unknown but, when basic infection control measures were reinforced, emphasizing
      the importance of hand antisepsis and judicious use of gloves, control of A.
      baumannii spread in the ward was achieved.

PMID- 15554516
TI  - [Prevalence of antibodies to Borrelia burgdorferi in Sardinian teen-agers].
AB  - A cross-sectional sero-epidemiological study was conducted on teen-agers in
      Northern Sardinia, a low risk population for Lyme borreliosis. The adjusted sero
      prevalence estimate for Enzyme Linked Immunofluorescent Assay on 443 teen-agers
      (229 males and 214 females) was 6.1%. The females vs males Odds Ratio was 5.1
      (CI95%: 2.1-12.8). The prevalence was associated with the family size (chi2 for
      trend: p=0.03); teenagers without cohabitants, except parents, had a five fold
      risk (CI95%: 1.2-20.7) of sero-positivity in comparison to those with wider
      families. No significant association was found with other socio-economical
      indices nor with pet-owning. In conclusion, positive Lyme serology is not common
      in Northern Sardinia, but further sero-epidemiological survey on at high-risk
      population (forestry workers, hunters, shepherds) are needed.

PMID- 15554517
TI  - [Vertical transmission of HGV and outcome of the infected babies].
AB  - To assess the risk of HGV mother-to-infant transmission and the clinical outcome
      of infected babies, we investigated 103 mother-infant couples and followed-up the
      infected children for 4-72 months. Twenty (19.4%) mothers were HGV-RNA positive
      and transmission occurred in ten (50%) babies; only one child acquired HGV and
      HCV infection. Maternal factors, such as history of intravenous drug use, HCV-RNA
      positivity, HIV coinfection, type of delivery and type of feeding were not
      related to HGV transmission. One HGV infected baby showed a mild hepatitis when
      he was also infected by Cytomegalovirus. Two babies cleared HGV within the first
      year of life. The HGV transmission rate is elevated but HGV infection seems to be
      benign, at least in a short-term follow-up.

PMID- 15554518
TI  - [HHV-6, new perspectives].
AB  - HHV-6 is the etiological agent of Exanthema subitum, and its role in human
      infection is well known. Recently, molecular diagnostics tools showed for HHV-6
      new pathogenetic features and new clinical implication. The present paper
      highlights recent knowledge on HHV-6 infection and presents a number of results
      concerning HHV-6 infection in children who had undergone BMT and concerning the
      roles of endothelial cells as viral reservoir.

PMID- 15554519
TI  - Gendered experiences of conflict and co-operation in heterosexual relations of
      Somalis in exile in Gothenburg, Sweden.
AB  - Political upheaval and poverty at home has been forcing many Somalis to
      immigrate. These immigrants do not only leave their physical house, families,
      relatives, loved ones, friends, but also familiarities, culture, customs, and
      often they do end up in no man's land being between their own and new home
      culture. Available reports suggest that there are about 15,000 Somalis in Sweden
      and their majority came here from late 1989 to 1996. About one third these
      immigrants live in and around the city of Gothenburg. This paper explores and
      describes gendered experiences of conflict and co-operation in heterosexual
      relations of Somalis in exile in Gothenburg, Sweden. A qualitative sociological
      in-depth interviews with 6 women and 7 men was performed during May 1999 to
      January 2000. A follow up focus group interviews with 10 people (2 women and 8
      men) was also carried on. The results show that both the Somali culture and
      Muslim religion do not support the children being taught sex education in schools
      or the names of the sex organs being pronounced other than to be used as
      metaphors. The girls, unlike their age group males, experience a very painful and
      terrifying process during childhood in which their self-esteem is downgraded by
      means of serious degrading traditional active violence such as female genital
      mutilation and visible virginity control. The narratives tell stories in which
      Somali women are degraded and expected to obey in situations characterised by
      their man's arbitrariness. They are subject to a very extensive form of social
      control, which is especially pronounced on issues regarding sexuality. Their
      integrity as women is, consequently set aside. When Somali refugees came to
      Sweden some of them came to adopt much of the modern lifestyle and cultural norm
      systems, preferable young people and some of the females. Relating to a new
      culture with its new expectations on the norm obedience also created changes in
      self-esteem. Exile situation tends to generate horizontal conflicts, among
      spouses and between groups of people. It also tends to generate vertical
      conflicts because now generations stand up against each other and this is
      especially pronounced when it is about issues of sexuality and sexual relations.
      The young generations questions their parents authority. They are now living in
      new social context and perceive risks, as well as possibilities. Their new dreams
      and choices, however, do not fit their parents' expectations, which sometimes
      leads to big problems. From a traditional perspective these deviants lack of
      respect for traditions and the original culture. From a male perspective this
      means more specifically a lack of respect for male dominance and superiority.

PMID- 15554520
TI  - Experiences against HIV/AIDS/STDS of Somalis in exile in Gothenburg, Sweden.
AB  - Since 1989, the City of Goteborg Immigrant Services Administration has been
      making efforts to inform about HIV/AIDS. The purpose has been to ensure that even
      immigrant residents of the City of Goteborg (Gothenburg) have access to relevant
      information about HIV/AIDS. The administration's efforts have been a part of the
      collected efforts of Gothenburg to prevent the spreading of HIV. This paper
      attempts to discover and describe experiences against HIV/AIDS/STDs of Somalis in
      Exile in Gothenburg, Sweden. A qualitative sociological in-depth interviews with
      13 individuals (6 women and 7 men) and with semi-structured and themetized
      emerging design was carried on. A follow up focus group interviews with 10
      individuals (2 women and 8 men) was also performed. The paper reveals that the
      general understanding of subjects on the issues under discussion is almost the
      same though details may vary from one research participant to the other. They
      have described this through narratives. STDs and specially HIV/AIDS was perceived
      as something dishonourable by the subjects. The HIV/AIDS is perceived as a sin
      which Allah sends to punish those who have fornication or sex without marriage
      (Zinna). Of course, this tendency of shying off the problem leads to ignorance of
      how to behave, which in turn decreases the risk of perceptions and as a result
      may also increase the risk of being infected. As concerns protection as a
      preventive measure, attitudes vary. The traditionalists have argued that condom
      increased the possibility of promiscuity or fonication, while young and more
      modern people saw condom as something good. We may conclude that Somalis who have
      arrived in Western world and in Sweden as adults did never have a modern sexual
      education for themselves due to socio-cultural reasons and this has important
      implication for giving proper information to their children about sex organs,
      human sexual development and preventive measures against HIV/AIDS/STDs. These
      immigrant parents should be offered culturally sensitive communication and
      educational programmes aimed at raising their awareness about teenagers sexuality
      and the preventive measures against HIV/AIDS/STDs.

PMID- 15554521
TI  - Non compliance to therapeutic prescriptions in paediatric patients: role of
      social communication.
AB  - The aim of this pilot study was to identify prevalent non-compliance behaviour in
      paediatric antibiotic therapy and to investigate the possible role of its social
      correlates. Patients' parents were surveyed at two paediatric practices in
      Catania, Italy, using an interviewer-administered questionnaire. The two
      practices were chosen for their location, in two different urban areas, to
      represent different sets of parents in terms of social status. Anticipated
      suspension of prescribed antibiotic therapy was the most frequently encountered
      form of non-compliance, shown by 41.2% of the parents. After partitioning the
      sample by mothers' occupational status--housewives versus working women-
      anticipated suspension revealed a positive association with educational level
      among the former group and a negative one, although not statistically
      significant, among the latter. Exposition to mass media messages about bacterial
      antibiotic resistance appeared to be a key intervening variable in interpreting
      these results, especially among more educated parents. Non-compliance was also
      associated with perceived characteristics of doctor-parents communication,
      particularly, with parents' perceived understanding of prescribed therapy.

PMID- 15554522
TI  - [Knowledge of nursing students about occupational biological risk].
AB  - The health care staff is potentially more exposed to contract infectious diseases
      at work. This risk becomes true if the DPI are not utilized and the operators
      don't work according to the standard protocol, and, with regard to the health
      care students, they begin their clinical training without the right knowledges.
      To verify the adequacy of knowledges and the consequent behaviours we effected a
      study among the students at first year of the D. U. for nurses in the University
      of L'Aquila, through a questionnaire. It came out many gaps of knowledges about
      the standard practice and about the Universal Precautions in about 20% of the
      interviewed.

PMID- 15554523
TI  - [Surgical chemoprophylaxis in the Emilia Romagna region].
AB  - The aim of this study is to assess the compliance with evidence based medicine of
      the practices of administration of perioperative surgical chemoprophylaxis in the
      Emilia Romagna region. Prospective study of 1 month duration including 31 of the
      36 public hospital existing in the region. For all the patients admitted to one
      of the 121 participating units and undergoing a surgical operation, data were
      collected on the surgical prophylaxis administered, including type of antibiotic,
      time of administration and duration. Surgical prophylaxis was given in 4,946
      surgical operations of the 6,167 included in the study. The median frequency of
      surgical prophylaxis administration was 81% ranging from 67% to 97% in different
      Local Health Authorities. Chemoprophylaxis was given also for surgical operations
      where, according to systematic literature reviews, the cost-benefit ratio is
      absolutely unfavourable to the use of antibiotics. In 2,120 cases (42.9%) the
      time of administration was not perioperative and, thus, differed from the
      recommended practice: in 264 cases (5%), antibiotics were administered after the
      operation. In 42.6% of the cases the duration of administration was not a short
      term prophylaxis, being longer than 24 hours: in these 2,108 cases, the median
      duration was 4 days ranging form 1 to 90 days. In 48% of the cases cefazolin was
      administered; in 1,347 cases (23.4%), instead, a third or fourth generation
      cephalosporin was used. The survey pointed out an overuse of antibiotics, both
      for indications and duration, even when clear evidences of efficacy are lacking;
      moreover, the criteria for selection of specific antibiotics frequently did not
      take into account the risk of selecting antimicrobial resistance strains.

PMID- 15554524
TI  - [Satisfaction of parents or accompanying persons with vaccination services for
      children and youngsters being vaccinated].
AB  - A patient satisfaction survey aimed to assess the quality of immunization
      services was carried out as part of the new regional vaccination plan launched in
      Piemonte in 1999 to comply with the targets of the national immunization program.
      In January and February 2001, persons accompanying children for vaccination at
      the outpatient clinics were requested to fill a self-administered questionnaire
      with questions on the organization of the immunization services, the health care
      facilities, the attitude of the health care workers and the quality of the
      information provided. The response rate was 93%. Overall, satisfaction with the
      immunization services scored generally high, except for the quality of the
      information provided to the public. Many interviewees complained that the
      written/verbal information about the vaccination schedules was either lacking or
      insufficient. The survey results indicate a need for better training and updating
      of health care workers so that they can give immunization service users correct
      information as requested.

PMID- 15554525
TI  - [Hospital infection prevention in an intensive care unit].
AB  - Aim of the study was to evaluate the efficacy of the hospital infection
      preventive procedures adopted in the intensive care unit (ICU) of the "S. Camillo
      Forlanini" hospital in Rome. First the following prevention protocols were
      analysed: invasive procedures (intubation, CVC and urinary catheter),
      surveillance cultures, infection management and antimicrobial prophylaxis.
      Comparison with international guidelines was carried out and protocols
      enforcement by the personnel was verified. Secondly a one year longitudinal
      surveillance study was performed in order to monitor the following site-specific
      infection rates: pneumonia (PNE), blood stream infections (BSI), urinary tract
      infections (UTI), surgical site infections (SSI). According to CDC definitions
      all patients developing infection 48 hours or more after ward admission were
      included. Furthermore risk factors (i.e. age, sex, SAPS II), invasive procedures
      (i.e. endotracheal intubation, vascular and urinary catheterisation),
      microbiological isolates and their antibiotic susceptibility were screened.
      Overall 302 patients (191 men and 111 women) were admitted; age 55.1 +/- 20.7
      years (mean), SAPS II 42.4 +/- 16.2 (mean) and average ward stay 12.5 +/- 21.7
      days. Crude mortality was 15.9%. Results showed a total of 37 infection episodes
      (20 PNE , 7 BSI, 8 UTI and 2 SSI) in 33 patients (10.9%). Infection and mortality
      rates were among the lowest registered in other italian ICU's. Standardized
      infection rates associated to invasive procedures were: Ventilator-associated PNE
      rate (7.8/1000), central venous catheter-associated BSI rate (2.2/1000), urinary
      catheter-associated UTI rate (2.1/1000). The first (PNE) was higher than the NNIS
      mean rate, whwreas BSI and urinary catheter associated rates were minor than the
      mean rates reported by NNIS. Gram-negatives were 61.7%, gram-positives 27.6% and
      Candida spp. 10.6%. The results confirm the ICU successful preventive strategy.

PMID- 15554526
TI  - [Preventive measures suggested to protect health workers from the risk due to a
      potential exposure to SARS agents].
AB  - The Authors describe the personal and environmental preventive measures suggested
      to protect health workers from the risks due to a potential exposure to SARS
      agents. The Authors stress the need that workers are allowed to wear individual
      protective disposable complying with technical regulations in order to be assured
      the best protection.

PMID- 15554527
TI  - [SARS: diagnosis, therapy, and especially prevention].
AB  - The main purpose of this review is to analyze some aspects of the severe acute
      respiratory syndrome, SARS, in order to obtain useful data to suggest preventive
      actions to reduce the spreading of the disease. Many elements have been examined
      to reach some conclusions and to allow an updated discussion. Surgical masks
      protect more the patient than the caregiver. Simple or double surgical masks may
      be useful, as double gloving protects the hands of the surgical personnel against
      percutaneous transmission of HIV eventually present in contaminated blood. The
      frequent substitution of the external masks with a new one will improve the
      filtering activity against droplets produced by cough or sneezes of the patient.
      The use of respiratory masks may be suggested in hospitals or in restricted
      ventilated areas where, even if coronavirus variant is considered an
      environmental contaminant more than a respiratory risk, droplets nuclei may
      persist in the air and add consistent dangers to the heath-care givers.
      Considering that large and medium droplets may infect floors and surfaces, in
      addition to gloves, gowns, masks and eyes protection, the available list of viral
      and bacterial factors implicated in SARS ethiology suggests a better hand
      antisepsis using frequently the alcohol based gels (containing an high percentage
      of emollients substances), if available. A liquid soap with triclosan can also be
      used, if the health-care workers compliance to hand washing increases, as
      expected in this explosive situation. On the basis of the results of some
      experimental data, the environmental disinfection may be effected with ethyl
      alcohol 70% in water. Disinfection of floors or larger surfaces may be obtained
      with chlorine compounds solutions, after an accurate pre-cleaning. When
      corrosion, bleaching or gas production have to be avoided, chlorine compounds may
      be substituted by phenolic detergent disinfectants.

PMID- 15554528
TI  - [Overweight and obesity].
AB  - Being over-weight and obesity are conditions which are becoming ever more common
      and this trend presents a series of social and psychological problems, apart from
      the well known health risks such as hypertension, heart disease, type 2 diabetes,
      orthopaedic problems, cancers of the endometrium and breast etc. The prevention
      and control of excess weight and obesity is largely based on adopting a healthy
      lifestyle and above all on diet and exercise. These ideas are also included in
      the Health Plan for 2002-2004, and are among the ten most important strategic
      objectives for promoting healthy living, disease prevention and informing the
      public on health matters.

PMID- 15554529
TI  - [Adolescent nutrition promotion: real and false problems].
AB  - This study shows the relationship between BMI of 3000 adolescents and their
      perceived-weight status, and the strategies for weight loss. The finding indicate
      that substantial numbers of teenage females perceive themselves as overweight
      when BMI suggest they are not, while males have a reasonably accurate weight.
      Diet was the most frequently selected method for losing weight especially among
      females that wrongly perceive themselves overweight (O.R. = 5.54 I.C. 95% 4.28
      7.19); while males were as likely to use diet as a strategy to lose weight only
      if they were really overweight (O.R. = 6.00; I.C. 95% 2.26-15.92). Exercise was
      selected as a method for losing weight by males independently to be overweight
      and by females only that perceive themselves overweight. The study shows that the
      young people of Sardinia need a health program to empower their knowledge the
      difference between health and aesthetic.

PMID- 15554530
TI  - [Enteric viruses and bacteriological parameters in molluscs].
AB  - Eighty-seven samples of shellfish were collected considering: type of mollusc,
      origin, growing area, monitoring or for human purpose. The bacteriological
      parameters were: Fecal Coliforms, Escherichia coli, and Salmonella; whereas the
      virological parameters included: Hepatitis A and E virus, Rotavirus, Astrovirus
      and Enterovirus. In total, 63.2% of samples had normal bacteria values, only one
      sample was Salmonella positive. The percentage of positive samples for Hepatitis
      A virus was 5.7%, Rotavirus 29.9%, Astrovirus 27.6%, Enterovirus 10.3%. The
      recovery of hepatitis E virus was always negative, whereas 13 samples (14.9%)
      were positive for two viruses.

PMID- 15554531
TI  - [Mycobacteria in swimming pool water and the meaning of microbiological
      conventional indicators].
AB  - Monitoring program of hygienic quality water in twelve public swimming pools was
      performed. Legally required microbiological indicator parameters of safety for
      gastrointestinal illness were measured besides the analyses of Pseudomonas spp.
      and Staphylococcus spp. prevalence, frequency of recovery and number of
      nontuberculous mycobacteria. We detected positive samples for coliforms at lower
      rate (29.3%) than Pseudomonas (75.5%), Staphylococcus spp. (46%) and Mycobacteria
      (59.4%). We pointed out statistically significant correlation (r=0.67 p=0.0001)
      between Mycobacteria and Pseudomonas so we think that the latter might be a good
      predictive marker. As 82% of samples had free chlorine residual within the limits
      stated by Italian Laws, the efficacy of chlorination to prevent risk of
      infectious diseases transmission by route other than gastroenteric was discussed.
      A revision of both the sanitary significance of conventional microbial parameters
      and the related regulations appears necessary.

PMID- 15554532
TI  - [Water resources destined for human consumption: qualitative monitoring].
AB  - The work is a synthesis of the qualitative monitoring on waters resources
      (specially surface water), that were potable and distributed as drinkable waters
      in north Sardinia between 1996-2002. The obtained results point out: for the
      surface waters, recurrent problems of elevated turbidity, color, oxidability,
      microbial contamination and eutrofication; for the ground waters, lower levels of
      pollutants even if an high content of natural elements and substances that, for
      as of natural origin, could endanger and limit the use as drinkable water
      (sodium, chlorides, iron, manganese). Drinking water plants have, largely, solved
      the main causes of ineffectiveness of treatment such as the demolition of the
      organic load and the formation of trihalomethanes but it as been found an high
      concentration of chlorites; occasionally, the values of ammonia, aluminum, iron,
      manganese and, rarely, trihalomethanes are out law in piped.

PMID- 15554533
TI  - [Microorganisms surviving in drinking water systems and related problems].
AB  - Drinking water in distribution systems may show abnormal values of some
      parameters, such as turbidity, and may support particular phenomena, such as
      bacterial regrowth or presence of Viable Not Culturable (VNC) bacteria. Turbidity
      can provide shelter for opportunistic microorganisms and pathogens. The Milwaukee
      outbreak (400,000 people) is one example of waterborne disease caused by the
      presence of pathogens (Cryptosporidium) in drinking water characterized by high
      and intermittent levels of turbidity. Bacterial regrowth in drinking water
      distribution systems may cause high increments of microorganisms such as
      heterotrophic bacteria, coliforms and pathogens. Microorganisms isolated from
      biofilm including Pseudomonas, Aeromonas, Legionella may have a significant
      health hazard especially in hospital areas. The presence of VNC bacteria in
      drinking water may represent a problem for their discussed role in infectious
      diseases, but also for the possibility of a considerable underestimation of true
      microbial concentrations in drinking waters. To study this kind of problems is
      necessary to apply suitable methods for drinking water analyses.

PMID- 15554534
TI  - [Hygienic aspects of the Tiber river: presence of pathogenic protozoa and
      correlation with microbiological and physico-chemical parameters].
AB  - An investigation on the hygienic quality of the Tiber river was conducted with
      the aim both to enumerate Giardia cysts and Cryptosporidium oocysts in the water
      and to determine possible correlations between them and bacterial indicators,
      pathogens and physico-chemical parameters. A low hygienic water quality was
      evidenced, with high counts of microorganisms. Furthermore, variable
      concentrations of Giardia and Cryptosporidium were observed. No correlation was
      found between the protozoa concentrations and that of the other microorganisms,
      whilst a significant correlation with redox potential and Giardia cysts was
      calculated.

PMID- 15554535
TI  - [The concentration of viruses in water using the tangential flow ultrafiltration.
      Recovery effectiveness in experimental conditions].
AB  - Poliovirus 1 concentration tests were carried out in artificially contaminated
      water by tangential flow ultrafiltration with Polisulfone filters 100000 MWCO.
      The tests were performed in 1 and in 20 liters of waters. The filters were
      conditioned and eluted respectively with Beef extract 3% and with glicina 1% at
      pH 7 and pH 9. The recovery mean using Beef extract resulted properly good, about
      the 83% and comparable to percentages we obtained in previous works with filters
      in cellulose nitrate and Virosorb filters. The viral recovery was low using the
      glicina for conditioning and eluting the filters.

PMID- 15554536
TI  - [Pharmaceuticals in the environment].
AB  - Drugs and their metabolites, once reached and spread over the soil and the
      aquatic environment, then exert their action on the living organisms belonging to
      such ecosystems. The present work provides a brief view on the main scientific
      experiences regarding the problem of the presence of drugs and/or their residues
      in the environment and of the related effects on the biokenosis and the human
      community.

PMID- 15554537
TI  - [Alkylphenols in the environment: a risk for human health?].
AB  - Endocrine Disrupting Chemicals (ECD) are a class of chemical compounds widely
      utilized for many industrial and civil applications and, consequently, widely
      diffused in the environment. Due to their chemical-physical characteristics, ECD
      may interfere with several endocrine functions in humans. Alkylphenols (APs),
      mainly produced by biodegradation of alkylphenols polyethoxylates surfactants,
      are a relevant group of ECD, both for their environmental diffusion and
      demonstrated estrogenic activity. Aim of this paper is to assess the potential
      risk of exposure to APs for humans, on the basis of the available data in
      literature concerning APs: environmental levels, accumulation in sediments and
      biota, toxicological effects on experimental animals.

PMID- 15554538
TI  - [Evaluation of genotoxic and/or co-genotoxic effects in cells exposed in vitro to
      extremely-low frequency electromagnetic fields].
AB  - During the last two decades, concerns have arisen regarding a possible
      association between extremely-low frequency (ELF) electromagnetic fields (EMF)
      exposure and cancer incidence (e.g. childhood acute leukaemia, cancer of the
      nervous system, and lymphomas). In 1979, Wertheimer and Leeper firstly reported
      an excess of cancer mortality among children living in homes located near power
      lines and presumably exposed to elevated magnetic fields. Subsequently, a large
      number of epidemiological studies investigated the possible association between
      residential or occupational exposure to ELF-EMF and cancer. Several in vivo and
      in vitro models have been investigated with the effort to determine a link, if
      any, between such fields and mutagenesis and to determine the possible mechanism
      of cancer risk. However, a causal relationship between exposure to ELF-EMF and
      cancer has been suggested but has not been unequivocally demonstrated. In 1998,
      following an analysis of the results retrieved in the literature, the U.S.
      National Institute of Environmental Health Sciences proposed to apply a "possible
      human carcinogen" category (Group 2B) to ELF-EMF. More recently, in 2002, the
      same classification for ELF-MF was proposed by the International Agency for
      Research on Cancer. In this in vitro approach, to test the genotoxic and/or co
      genotoxic potency of ELF-MF, we used the alkaline single-cell microgel
      electrophoresis (comet) assay and the cytokinesis block micronucleus test. Co
      exposure assays were performed in the presence of N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), 4-nitroquinoline N-oxide (4NQO), benzene, 1,4
      benzenediol (1,4-BD), or 1,2,4-benzenetriol (1,2,4-BT). An ELF-MF (50 Hz, 5 mT)
      was obtained by a system composed of capsulated induction coils. ELF-MF alone was
      unable to cause direct primary DNA damage. Whereas, an increased extent of DNA
      damage was observed in cells co-exposed to ELF-MF and MNNG, 1,4-BD, or 1,2,4-BT.
      An opposite trend was observed in cells treated with 4NQO and co-exposed to ELF
      MF. Moreover, the frequency of micronucleated cells in ELF-MF-exposed cells was
      higher than in control cultures. Our findings suggest that the tested ELF-MF (50
      Hz, 5 mT) possess genotoxic (micronucleus test) and co-genotoxic (comet assay)
      capabilities. The possibility that ELF-MF might interfere with the genotoxic
      activity of xenobiotics has important implications, since human populations are
      likely to be exposed to a variety of genotoxic agents concomitantly with exposure
      to this type of physical agent.

PMID- 15554539
TI  - [Knowledge of disinfection practices and behaviour of the nursing staff at a
      hospital].
AB  - The authors have carried a study on the knowledge of disinfection practices and
      the behaviour in operating room in order to control and prevent nosocomial
      infections. It is necessary for high percent of head nurses and nurses to have
      guidelines for the disinfection/sterilization procedures with the aim to avoid
      infections, but a large number of subjects don't know the correct procedures. The
      knowledge of a correct behaviour in the operating room is greater, although many
      of nursing staff don't wear the overshoes and the protective glasses. The
      statistical analysis show that nurses and the subjects with high degree have a
      greater knowledge of problems. It is important the planning of training and
      retraining courses directed to the improvement of technical knowledge and
      behaviour.

PMID- 15554540
TI  - [Factors related to in-hospital mortality after stroke in Lazio region, Italy].
AB  - The use of hospital discharge abstracts in estimating the outcome of hospital
      care represents an ongoing interest in public health. However standardized
      methodologies are still not available. We carried out a retrospective study to
      estimate the association between demographic and clinical characteristics and in
      hospital mortality after stroke by using administrative data from the Hospital
      Information System in Lazio Region. We also assessed the relationship between the
      presence of neurology services and the outcome. We found 12,781 incident episodes
      of stroke (main diagnosis ICD-9: 430-431-434-436) (49.3% male, mean age = 74
      years) admitted in 126 hospitals in the Lazio region for the period 1999-2000.
      From the hospital discharge abstracts we collected patient demographic and
      clinical data. The hospitals were classified in centres with and without
      neurology services. Admissions to hospitals with neurology services were
      evaluated as predictors of in-hospital mortality after adjustment for gender,
      age, residence, education, source of admission, type of stroke, heart disease,
      kidney disease and history of atrial fibrillation. In-hospital mortality (within
      30 day) was 25.1%. Female gender, advanced age, residence in Rome, urgent
      transport, kidney disease and history of atrial fibrillation were associated with
      an increased risk. Hemorrhagic stroke (ICD-9 = 430-431) had a worse outcome than
      ischemic stroke (ICD-9 = 434) and acute undefined cerebrovascular disease (ICD-9
      = 436). Patients admitted to hospitals with neurology services showed a
      significantly decreased risk (OR = 0.88, IC95% = 0.79-0.98), particularly in
      occlusion of cerebral artery (ICD-9 = 434) and in undefined cerebrovascular
      disease (ICD-9 = 436). Demographic and clinical variables are associated with the
      outcome of hospitalised stroke patients. Admissions of acute stroke patients in
      specialized hospitals seem to play a role in reducing the risk of in-hospital
      mortality.

PMID- 15554541
TI  - [Survey on accidental exposure to biological materials in the Hospital-University
      Complex of Sassari during the period 1995-2000].
AB  - To study professional exposure to biological materials an investigation was
      carried out in the Hospital-University Complex of Sassari during the period
      January 1st 1995-December 31 2000. 1003 occupational accidents were notified
      (incidence rate=6%). Infirmaries were the most at risk category (45%) and about
      the half part of the accidents occurred in surgical area (44.7%). The most
      frequent accident was needle puncture (53%); exposure involved principally the
      hands (76.3%). The basal serology of injured personnel showed low positivity for
      any HBV markers (72.7%), HCV (0.4%) and no positivity for HIV; while high levels
      were found among source patients. From the comparison between serological data
      (injured vs source), when ascertainable, emerged a biological hazard of 7.7% for
      HBV, 30.2% for HCV and 3.2% for HIV; however no seroconversions were observed at
      follow up. The study also pointed out the need of improve prevention programmes.

PMID- 15554542
TI  - [Microbial air monitoring in operating theatre: active and passive samplings].
AB  - Microbial air contamination was evaluated in 11 operating theatres using active
      and passive samplings. SAS (Surface Air System) air sampling was used to evaluate
      cfu/m3 and settle plates were used to measure the index of microbial air
      contamination (IMA). Samplings were performed at the same time on three different
      days, at three different times (before, during and after the surgical activity).
      Two points were monitored (patient area and perimeter of the operating theatre).
      Moreover, the cfu/m3 were evaluated at the air inlet of the conditioner system.
      74.7% of samplings performed at the air inlet and 66.7% of the samplings
      performed at the patient area before the beginning of the surgical activity (at
      rest) exceeded the 35 cfu/m3 used as threshold value. 100% of IMA values exceeded
      the threshold value of 5. Using both active and passive sampling, the microbial
      contamination was shown to increase significantly during activity. The cfu values
      were higher at the patient area than at the perimeter of the operating theatre.
      Mean values of the cfu/m3 during activity at the patient area ranged from a
      minimum of 61+/-41 cfu/m3 to a maximum of 242+/-136 cfu/m3; IMA values ranged
      from a minimum of 19+/-10 to a maximum of 129+/-60. 15.2% of samplings performed
      at the patient area using SAS and 75.8% of samplings performed using settle
      plates exceeded the threshold values of 180 cfu/m3 and 25 respectively, with a
      significant difference of the percentages. The highest values were found in the
      operating theatre with inadequate structural and managerial conditions. These
      findings confirm that the microbiological quality of air may be considered a
      mirror of the hygienic conditions of the operating theatre. Settle plates proved
      to be more sensitive in detecting the increase of microbial air contamination
      related to conditions that could compromise the quality of the air in operating
      theatres.

PMID- 15554543
TI  - [The balance between quality and resources in health care organizations: study on
      a hospital cleaning service managed in outsourcing].
AB  - The study analyses the performances of a hospital cleaning service managed in
      outsourcing with respect to the balance between available resources and expected
      quality standards. Data were referred to a high specialization hospital and were
      collected through a multiple approach (interviews, cost analysis, performance
      simulations and field investigations). A difference (48%) emerged between
      expected and observed standards. In order to quantify the estimated gap, two
      models were examined with respect to personnel costs (euro 7.09/hr for NHS
      personnel and euro 4.5/hr for private personnel). Additional resources needed to
      achieve required standards resulted respectively 182% and 115% of the invested
      budget. This result stresses the importance to define the minimum standard to be
      guaranteed for safe and clean environment in health care organizations and the
      break-even point between quality and costs, leaving the single institutions the
      decision about additional quality level and resources needed for it.

PMID- 15554544
TI  - [Quality of some working places in Milan].
AB  - Questionnaires were distributed to the responsibles and to the dependents of
      structures with high turnover of people, to have informations about numbers and
      typology of instruments, habits of dependents and type of cleanings. In these
      structures, microbiologic quality of air and of informatic instruments' surfaces
      were evaluated and efficacy of treatment with some products of cleaning and
      sanification was verified. Air microbiological contamination was comparable to
      that found in other similar researchs. Fecal contamination indicators were not
      found on instruments' surfaces, both before, and after treatment; in 8 cases (3%)
      Staphylococcus aureus was isolated and in 6 cases (2%) species of not pathogenous
      staphylococci were isolated. At the beginning of the working day, mean values of
      total aerobic bacterial count at 22 degrees and 37 degrees, were low, settled to
      zero after treatment and increased progressively during the week. Infective risk
      for workers can be considered insignificant because of low microbiological
      contamination. Specific sanification products seem not to be necessary, since
      common products of cleaning have the same efficacy.

PMID- 15554545
TI  - [Considerations on the evolution of the concept of zoonoses].
AB  - The existence of diseases common to humans and animals has been known since the
      beginning of history. The disease transmission from animals to people was first
      observed on rabies ("the mother of all zoonoses") and later on in occupational
      diseases (anthrax, glanders, "mange"); in time, also certain food-borne
      infections were included in this category. The microbiological era has first
      brought along the concept of infection, then that of zoonoses, which has extended
      and now numbers some 200 infections. The World Health Organization has been
      interested in zoonoses since its foundation. Zoonoses represent an important
      issue for public health, fundamental in veterinary public health, whose functions
      are here listed. This discipline is concerned with all health problems associated
      with direct and indirect relationships between humans and animals, including also
      non-communicable ones. It has been proposed, therefore, to extend the term
      zoonoses as follows: "Any detriment to the health and/or quality of human life
      deriving from direct or indirect relationships with (other) vertebrate, or edible
      or toxic invertebrate animals". Contributors (e.g. Blancou) suggest to remove
      "edible or toxic "from the definition. Examples of zoonoses are provided
      according to the extended concept.

PMID- 15554546
TI  - Is God in our genes? A provocative study asks whether religion is a product of
      evolution. Inside a quest for the roots of faith.

PMID- 15554547
TI  - He never gave up. What actor and activist Christopher Reeve taught scientists
      about the treatment of spinal-cord injury.

PMID- 15554548
TI  - No bones about it. It's almost Halloween, a good time to start thinking about
      your skeleton.

PMID- 15554549
TI  - Biomarkers--the key to the clinical development of chemopreventives.

PMID- 15554550
TI  - Studies on the chemopreventive potentials of vegetable oils and unsaturated fatty
      acids against breast cancer carcinogenesis at initiation.
AB  - The effect of dietary fat on breast cancer is a longstanding and an unresolved
      issue. We found that 17beta-estradiol (E2) could be activated by the epoxide
      forming oxidant dimethyldioxirane (DMDO) to bind DNA-forming DNA adducts both in
      vitro and in vivo, and to inhibit nuclear RNA synthesis. We proposed that E2
      epoxidation is the underlying mechanism for the initiation of breast cancer
      carcinogenesis (Carcinogenesis 17, 1957-61, 1996). This report is on the
      transcriptional and DNA-binding properties of vegetable oils and fatty acids, and
      on the potentials of these compounds to prevent the formation of E2 epoxide. The
      results show that vegetable oils, having no effect on nuclear RNA synthesis
      either before or after DMDO treatment, were all able to prevent the formation of
      E2 epoxide independent of their mono- or polyunsaturated fatty acid content.
      Similarly, unsaturated fatty acids, regardless of chain length and number of
      double bonds, were all able to prevent the formation of E2 epoxide as reflected
      by the loss of the ability of [3H]E2 to bind DNA. In contrast to vegetable oils,
      the results indicated that the unsaturated fatty acids palmitoleic, oleic,
      linoleic, linolenic and arachidonic acid could be activated by DMDO to inhibit
      nuclear RNA synthesis, and that the mono-unsaturated fatty acids (i.e.
      palmitoleic and oleic acid) were stronger inhibitors than fatty acids with more
      than one double bond (e.g. linoleic, linolenic and arachidonic acid). [32P]Post
      labeling analysis revealed that under identical DMDO activation, the DNA adducts
      formed for oleic acid were 17098 adducts/10(8) nucleotides, which was 20-fold
      more than palmitoleic acid (815), and 120-fold more than alpha-linolenic acid
      (142). This result strongly suggests that oleic acid could be a potential
      initiating carcinogen after epoxidation.

PMID- 15554551
TI  - Awareness of breast cancer incidence and risk factors among healthy women.
AB  - The efficacy of early breast cancer detection programmes seems to be mainly
      influenced by the awareness of breast cancer in general among healthy women. This
      study aimed to provide information about women's understanding of breast cancer
      incidence and risk of disease. Based on a newly developed questionnaire 2108
      healthy women were asked about their knowledge and perceptions in relation to
      breast cancer incidence, risk factors, risk perception and level of concern. Of
      these women 78.8% were well aware of breast cancer in general terms. However,
      there were major aspects such as incidence or risk factors that were poorly
      understood. Only one-third correctly estimated the incidence of breast cancer;
      95% understood breast cancer in the familial history as a risk factor, but only
      57% understood the age risk; 37.1% of women perceived hormonal contraceptives and
      35.9% hormonal replacement therapy as risk factors of breast cancer. The latter
      estimation was significantly higher in women above 40 years. Recommendations for
      the improvement of cancer prevention programmes include targeting understanding
      of lifetime risk of breast cancer, age as a risk factor, survival from breast
      cancer or hormonal factors. There is a need to separately address the perceptions
      of women depending on age, social status and educational levels.

PMID- 15554552
TI  - Public awareness of risk factors and screening for colorectal cancer in Europe.
AB  - Colorectal cancer (CRC) is the commonest site for malignancy in Europe. The
      Commissioner for Health wishes to promote screening for colorectal, breast and
      cervical cancer in Europe. The aim of this study was to assess public knowledge
      of CRC in Europe and likely take up of free screening. To this end 20710 members
      of the public from 21 European countries were interviewed by means of a regular
      survey amongst consumers (Omnibus survey) using 13 stem questions. Forty-eight
      per cent thought the population were at equal risk of CRC, only 57% were aware of
      age and 54% of family history as risk factors. Although 70% were aware of dietary
      factors, only 30% knew that lack of exercise might be a risk factor. Only 51% had
      knowledge of CRC screening but 75% were 'very', or 'quite interested, in taking
      up faecal occult blood (FOB) screening if offered free. Barriers to screening
      were lack of awareness of risk (31%), youth (22%) and an un-anaesthetic test
      (19%). There was a big cultural difference in willingness of the public to
      discuss bowel symptoms: there was a major barrier in Finland (91%), Britain
      (84%), Luxembourg (82%), Poland (81%) and Portugal (80%); less of a barrier in
      Spain (49%), Italy (44%) and Iceland (39%). In conclusion, the challenge of
      achieving high compliance for CRC screening must be a major objective amongst EU
      member states and non-aligned countries of Europe in the next decade, because it
      is known that the non-compliant group are those at greatest risk of death from
      CRC. This study has shown that awareness of CRC is low in Europe and that an
      educational programme will be essential to achieve high compliance for CRC
      screening as a means of reducing deaths from bowel cancer.

PMID- 15554553
TI  - Modulation of altered hepatic foci induction by diallyl sulphide in Wistar rats.
AB  - Diallyl sulphide (DAS) is a sulphur-containing volatile compound present in
      garlic (Allium sativum). It has been shown to inhibit a number of chemically
      induced forms of cancer in experimental animals. The present study demonstrates
      the inhibitory effect of DAS on the development of diethylnitrosamine (DEN)
      initiated and 2-acetyl-aminofluorene (2-AAF) promoted preneoplastic altered
      hepatic foci (AHF) in Wistar rats. AHF were scored and analysed by quantitative
      stereology using the Image Analysis system from frozen liver sections stained for
      biological markers, namely glutathione S-transferase, placental form (GST-P),
      gamma-glutamyl transpeptidase (GGT), adenosine triphosphatase (ATPase), glucose-6
      phosphatase (G6 Pase) and alkaline phosphatase (AlkPase). DAS-supplemented rats
      were found to restore the near-normal levels of enzymes GST-P and GGT when
      exposed to DEN and 2-AAF. DAS administration following DEN and 2-AAF exposure led
      to the restoration of enzymic activity of ATPase, G6 Pase and AlkPase, as evident
      by number and area of the foci. These findings suggest the protective role of DAS
      in rat hepatocarcinogenesis, by suppressing DEN- and 2-AAF-induced AHF
      development.

PMID- 15554554
TI  - Regional trends in Portuguese gastric cancer mortality (1984-1999).
AB  - The international decline in gastric cancer is mainly attributed to improved
      socio-economic conditions. However, some southern and eastern European countries
      showed slower and later decline, reflecting a less favourable general environment
      The same probably applies to regional differences within countries, making
      national indicators potentially misleading. Fitting log-linear Poisson models we
      compared trends in gastric cancer mortality (1984-1999) across 18 Portuguese
      regions. Pearson correlation coefficients were computed to assess the regional
      association between decline in cancer mortality and baseline cancer mortality and
      variation in indices of social development and medical care. National gastric
      cancer mortality changed -2.0% year in men and -2.2% year in women. The regional
      yearly variation in mortality ranged from -3.5% [95% confidence interval (CI) 
      4.5 to -2.5] to -0.6% (95% CI -1.4 to 0.2) in men, and from -3.7% (95% CI -4.8 to
      -2.7) to -0.8% (95% CI -1.6 to 0.0) in women. Regional variation was not
      significantly associated with baseline gastric cancer mortality (r = 0.18, P =
      0.47), but with the variation in post-neonatal mortality (r = 0.59, P = 0.01). In
      Portugal, gastric cancer shows a wide regional variation in frequency trends. The
      correlation with known indicators of social and economic development indicates
      that future improvement in gastric cancer rates is expected in parallel with a
      more widespread development.

PMID- 15554555
TI  - P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in
      Greek women.
AB  - The polymorphism of codon 72 in the p53 tumour suppressor gene has been
      associated in the last decade with the risk of developing various neoplasias. An
      influence of this polymorphism on ovarian and endometrial cancer has also been
      suggested. We examined the genotype frequency of this polymorphism in archival
      samples from 56 patients with endometrial neoplasias and 51 patients with ovarian
      neoplasias. Cervical smears from 30 healthy, human papillomavirus (HPV)-negative
      women with normal cytology and colposcopy, served as control sample. Women with
      ovarian neoplasias, especially adenocarcinomas, had Arg/Arg more often than
      healthy controls [odds ratio (OR) 4.16 at P = 0.0058]. No statistically
      significant difference was found between women with endometrial cancer and
      controls. Differentiation of ovarian tumours did not appear to be associated in a
      statistically significant manner with the genotype, whereas a positive linear
      trend of Arg/Arg towards poor differentiation was noted in endometrial
      malignancies (mainly endometrioid adenocarcinomas). Our results suggest that
      homozygous arginine at codon 72 of p53 may represent a risk factor for developing
      ovarian malignancies and may affect the differentiation of endometrial cancer.
      Further studies need to be carried out in order to establish the clinical use of
      this polymorphism for risk assessment and possibly outcome prediction of ovarian
      and endometrial neoplasias.

PMID- 15554556
TI  - Risk of non-Hodgkin's lymphoma and skin malignancies in patients diagnosed with
      cataract.
AB  - The rapid increase of non-Hodgkin's lymphoma (NHL) in industrialized countries is
      yet unexplained. Ultraviolet radiation (UVR) has been suggested as an aetiologic
      factor due to observed elevated risks of cutaneous malignancies after NHL and
      vice versa. Cataract, as related to UVR, was tested as a proxy variable to
      further elucidate this observation. Cataract in-patients (n = 49914) reported to
      the Swedish Patient Register and later developing NHL and cutaneous malignancies
      were identified by record linkage to the Swedish Cancer Registry. The observed
      number of malignancies among cataract patients did not differ significantly from
      that expected in the general population. In contrast, the risk of cutaneous
      malignant melanoma was lower than anticipated, based on Swedish background
      incidence figures. The results did not give support for a causal relationship
      between NHL and UVR.

PMID- 15554557
TI  - Population-based incidence and mortality cancer trends (1986-1997) from the
      network of Italian cancer registries.
AB  - The objective of this study was to analyse incidence and mortality cancer trends
      in the Italian Network of Cancer Registries (about 8,000,000 inhabitants) during
      the period 1986-1997. Included were 525,645 newly diagnosed cancers and 269,902
      cancer deaths (subjects > 14 years). Joinpoints (points in time where trend
      significantly changes from linearity) were found and estimated annual percentage
      changes (EAPC) used to summarize tendencies. Overall cancer incidence increased
      in both sexes and cancer mortality significantly decreased (since 1991 among
      men). Lung cancer showed significantly decreasing incidence (EAPC = -1.4%) and
      mortality (EAPC = -1.6%) among men and increasing trends among women. In women,
      breast cancer incidence significantly increased (EAPC= +1.7%) and mortality
      decreased since 1989 (EAPC= -2.0%). Stomach cancer incidence and mortality
      decreased in both sexes. Prostate incidence sharply increased since 1991 and
      mortality decreased. Colon cancer incidence increased and rectum mortality
      decreased significantly in both sexes. Significant increases in incidence were
      also found for kidney (up to 1991 among men), urinary bladder, skin epithelioma,
      melanoma, liver (up to 1993 among men), pancreas, mesothelioma, Kaposi's sarcoma
      (up to 1995 among men), testis, thyroid, non-Hodgkin's lymphomas and multiple
      myeloma. Mortality significantly decreased for cancers of the oral cavity and
      pharynx, oesophagus, liver (women), larynx (men), bone, cervix (since 1990),
      central nervous system, urinary bladder, thyroid, Hodgkin's lymphomas and
      leukaemias (men). Non-Hodgkin's lymphoma mortality increased in both sexes. In
      conclusion, most of the changes seen can be explained as the effect of changes in
      smoking habits and of the extension of secondary prevention activities. The
      Italian health care system will also have to cope with growing cancer diagnostic
      and therapeutic needs due to population ageing.

PMID- 15554558
TI  - Protein biomarkers and drug design for cancer treatments.
AB  - The development of new cancer treatments is quickly evolving away from
      traditional practices of the last 25 years. This change is occurring not only at
      the technical level, but also conceptually as the human genome is unravelled and
      decades of research contribute to our understanding of the molecular complexity
      of this disease. It is anticipated that disease initiation and progression is
      dictated by an understandable set of acquired capabilities. Knowledge of the
      molecular events associated with these acquired capabilities will allow the
      development of targeted agents coupled with new biomarkers for the prevention of
      cancer progression. This will have a profound influence on how drugs are
      developed, approved, and used by the medical community. The Food and Drug
      Administration (FDA) has over 400 Investigational New Drug (IND) applications for
      cancer in its portfolio, which increasingly involve molecular targets and genomic
      applications. However, only one-fifth of IND agents succeed in New Drug
      Application (NDA) and there is more expense and uncertainty around successful
      drug development than ever before. Biomarkers should help the success rate of
      INDs by enhancing the link between target and disease as well as in improving
      patient selection and monitoring response. In this review, we discuss how
      biomarkers can be used for target validation and pharmacodynamic modeling in
      preclinical drug discovery. We then explore the use of biomarkers in clinical
      development from proof of mechanism to proof of concept studies, as well as their
      use in the prevention setting.

PMID- 15554559
TI  - Protein biomarkers for breast cancer prevention.
AB  - Protein biomarkers suitable for the prevention of breast cancer must be extremely
      sensitive, easily detectable and highly correlated with the disease. They should
      be expressed in the reversible phase of carcinogenesis. Among the large number of
      candidate tumour-associated proteins, those related to the oestrogen/chorionic
      gonadotropin/insulin pathway seem to be of most interest because these can be
      causally implicated. They presumably are the first to express differently and are
      open to hormonal treatments. The biomarkers that give information on membrane
      receptor-modulated signal transduction should be considered as well. Up to now,
      only tamoxifen has shown some preventive activity, suggesting that the oestrogen
      pathway is useful indeed. Fenretinide and recombinant human chorionic
      gonatotropin (hCG) are also promising. But the financial requirements and the
      very long assessment periods largely prevent current research. This is precisely
      why we badly need to give priority to molecular biology research, in particular
      in the protein compartment There is widespread belief that advanced proteomics
      together with increased informatics can provide specific combinations of disease
      related expression profiles that could identify high-risk groups with much more
      reliability and allow us to monitor preventive strategies.

PMID- 15554560
TI  - Olives and olive oil in cancer prevention.
AB  - Epidemiologic studies conducted in the latter part of the twentieth century
      demonstrate fairly conclusively that the people of the Mediterranean basin enjoy
      a healthy lifestyle with decreased incidence of degenerative diseases. The data
      show that populations within Europe that consume the so-called 'Mediterranean
      diet' have lower incidences of major illnesses such as cancer and cardiovascular
      disease. Studies have suggested that the health-conferring benefits of the
      Mediterranean diet are due mainly to a high consumption of fibre, fish, fruits
      and vegetables. More recent research has focused on other important factors such
      as olives and olive oil. Obviously fibre (especially wholegrain-derived
      products), fruits and vegetables supply an important source of dietary
      antioxidants. What is the contribution from olives and olive oil? Apparently the
      potential is extremely high but epidemiologic studies rarely investigate
      consumption of these very important products in-depth, perhaps due to a lack of
      exact information on the types and amounts of antioxidants present. Recent
      studies have shown that olives and olive oil contain antioxidants in abundance.
      Olives (especially those that have not been subjected to the Spanish brining
      process) contain up to 16 g/kg typified by acteosides, hydroxytyrosol, tyrosol
      and phenyl propionic acids. Olive oil, especially extra virgin, contains smaller
      amounts of hydroxytyrosol and tyrosol, but also contains secoiridoids and lignans
      in abundance. Both olives and olive oil contain substantial amounts of other
      compounds deemed to be anticancer agents (e.g. squalene and terpenoids) as well
      as the peroxidation-resistant lipid oleic acid. It seems probable that olive and
      olive oil consumption in southern Europe represents an important contribution to
      the beneficial effects on health of the Mediterranean diet.

PMID- 15554561
TI  - Mediterranean diet, antioxidants and cancer: the need for randomized trials.
AB  - In nutritional epidemiology the traditional approach has been to assess single
      nutrients or food items. Now, a growing interest exists in dietary patterns. The
      study of dietary patterns with a whole-diet approach represents a needed and
      complementary methodology. Among a priori defined patterns, the highly palatable
      traditional Mediterranean diet has many options to be the first choice in the
      dietary prevention of cancer. However, sound epidemiologic evidence about its
      ability to prevent the most frequent cancers is scarce. In conjunction with large
      and well-designed cohort studies, randomized trials using a whole-diet approach
      and not a simple antioxidant supplement are needed in Mediterranean countries.

PMID- 15554562
TI  - The role of antioxidants in the mediterranean diets: focus on cancer.
AB  - The incidence of certain cancers in the Mediterranean area is lower than in other
      areas of the world (e.g. in northern Europe and the USA). As nutrition and
      dietary factors comprise one of the three major factors for human carcinogenesis,
      the hypothesis was formulated that the dietary profile of the Mediterranean diet,
      rich in antioxidants, might exert preventive actions. Alas, the vast majority of
      experiments to prove this hypothesis have been obtained in vitro, and most of the
      necessary information on the absorption, distribution and metabolism of
      oligonutrients is currently lacking. Yet, even though the exact role of
      antioxidants in the Mediterranean diet is yet to be fully established, data from
      observational studies are strong enough to reinforce the notion that a diet low
      in saturated fat and alcohol and rich in plant food and whole grain, such as the
      traditional Mediterranean diet, is associated with lower risk of cancer and
      should be actively promoted.

PMID- 15554563
TI  - Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit
      extracts in a mouse mammary organ culture.
AB  - We previously reported anticancer effects of pomegranate extracts in human breast
      cancer cells in vitro and also chemopreventive activity of pomegranate fermented
      juice polyphenols (W) in a mouse mammary organ culture (MMOC). In the present
      study we decided to expand the MMOC investigations to also include an evaluation
      of the potential chemopreventive efficacy of a purified chromatographic peak of W
      (Peak B), and also of whole pomegranate seed oil. In brief, an MMOC was
      established according to a known method. For the first 10 days of culture, the
      glands were treated with pomegranate fermented juice polyphenols (W), a high
      performance liquid chromatographic (HPLC) peak separated from W (peak B), or
      pomegranate seed oil (Oil, and on day 3, exposed to the carcinogen 7,12
      dimethylbenz[a]anthracene (DMBA), and for 10 days treated with the putative
      pomegranate chemopreventive. The glands were subsequently harvested and tumours
      counted by visual inspection. While W effected a 42% reduction in the number of
      lesions compared with control, peak B and pomegranate seed oil each effected an
      87% reduction. The results highlight enhanced breast cancer preventive potential
      both for the purified compound peak B and for pomegranate seed oil, both greater
      than that previously reported for pomegranate fermented juice polyphenols.

PMID- 15554564
TI  - Hormone replacement therapy and risk of lymphomas and myelomas.
AB  - The relation between post-menopausal hormone replacement therapy (HRT) and
      lymphoid neoplasms was analysed using data from a case-control study conducted in
      northern Italy between 1983 and 1992. Cases included 26 incident, histologically
      confirmed, post-menopausal female patients of Hodgkin's Disease (HD), 145 non
      Hodgkin's lymphomas (NHL) and 65 multiple myelomas (MM), between 45 and 79 years
      of age. The control group comprised 361 women (age range 45-79 years) admitted to
      the same network of hospitals for acute, non-neoplastic conditions. The
      multivariate odds ratio (OR) for ever HRT users was 0.7 [95% confidence interval
      (CI) 0.2-2.8] for HD, 0.7 (95% CI 0.3-1.4) for NHL, and 0.2 (95% CI 0.1-1.0) for
      MM. No clear pattern of association was found for duration or recently of use.
      Despite the relatively small number of cases, due to the rarity of the disease,
      and the low frequency of HRT use in this population, these findings provide
      additional information for any global risk-benefit assessment of HRT use.

PMID- 15554565
TI  - The joy-riding pig.

PMID- 15554566
TI  - Biliary nitrate and risk of carcinoma of the gallbladder.

PMID- 15554567
TI  - Why is self-help neglected in the treatment of emotional disorders? A meta
      analysis.
AB  - BACKGROUND: Although the burden of emotional disorders is very high, mental
      health care is only available to a minority of patients. The literature suggests
      that self-help strategies, both bibliotherapy and self-help groups alike, are
      effective for various, less serious complaints but it is unclear whether
      available data support a role for self-help in treatment protocols for patients
      with clinically significant emotional disorders. METHOD: We searched the
      literature with a focus on 'anxiety' and/or 'depressive disorder'. Standardized
      assessment of diagnosis or symptoms and randomized controlled trials were
      inclusion criteria for a meta-analysis. RESULTS: The mean effect size of self
      help (mainly bibliotherapy) v. control conditions is 0.84, and 0.76 for follow
      up; the effect sizes of self-help v. treatment are -0.03 and -0.07 respectively.
      A longer treatment period is more effective. CONCLUSIONS: Bibliotherapy for
      clinically significant emotional disorders is more effective than waiting list or
      no treatment conditions. The dearth of studies on self-help groups for emotional
      disorders does not permit an evidence-based conclusion concerning the effects of
      self-help groups. No difference was found between bibliotherapy and psychiatric
      treatment of relatively short duration.

PMID- 15554568
TI  - Efficacy and safety of methylphenidate in 45 adults with attention
      deficit/hyperactivity disorder. A randomized placebo-controlled double-blind
      cross-over trial.
AB  - BACKGROUND: Data on the efficacy and safety of methylphenidate in adults with
      attention deficit/ hyperactivity disorder (ADHD) are lacking in Europe. This
      study was undertaken to report on the efficacy and safety of methylphenidate in
      an adult out-patient population with ADHD, and to compare results with US data.
      METHOD: A double-blind randomized cross-over trial comparing methylphenidate and
      placebo in 45 adults with ADHD with childhood onset was performed in a dose
      titration design. Methylphenidate was titrated from 0.5 mg/kg per day in week 1
      up to 1.0 mg/kg per day in week 3. RESULTS: Response rates using methylphenidate
      varied between 38 and 51%, and using placebo between 7 and 18% (p<0.05),
      depending on outcome measure used. Although the overall percentage of subjects
      having any side effect on both methylphenidate and placebo was rather high, side
      effects on methylphenidate over and above those on placebo were few and mild.
      CONCLUSIONS: Methylphenidate proves to be an effective and well tolerated
      treatment for symptoms of ADHD in adults in the short term. Future research
      should study the long-term response and clarify the impact of gender, co
      morbidity, socio-economic status and IQ on response rates in adults with ADHD.

PMID- 15554569
TI  - A group intervention which assists patients with dual diagnosis reduce their drug
      use: a randomized controlled trial.
AB  - BACKGROUND: There is a well-recognized association between substance use and
      psychotic disorders, sometimes described as 'dual diagnosis'. The use of
      substances by people with psychosis has a negative impact in terms of symptoms,
      longitudinal course of illness and psychosocial adjustment. There are few
      validated treatments for such individuals, and those that do exist are usually
      impracticable in routine clinical settings. The present study employs a
      randomized controlled experimental design to examine the effectiveness of a
      manualized group-based intervention in helping patients with dual diagnosis
      reduce their substance use. METHOD: The active intervention consisted of weekly
      90-min sessions over 6 weeks. The manualized intervention was tailored to
      participants' stage of change and motivations for drug use. The control condition
      was a single educational session. RESULTS: Sixty-three subjects participated, of
      whom 58 (92%) completed a 3-month follow-up assessment of psychopathology,
      medication and substance use. Significant reductions in favour of the treatment
      condition were observed for psychopathology, chlorpromazine equivalent dose of
      antipsychotics, alcohol and illicit substance use, severity of dependence and
      hospitalization. CONCLUSIONS: It is possible to reduce substance use in
      individuals with psychotic disorders, using a targeted group-based approach. This
      has important implications for clinicians who wish to improve the long-term
      outcome of their patients.

PMID- 15554570
TI  - Cost-effectiveness of cognitive behavioural therapy, graded exercise and usual
      care for patients with chronic fatigue in primary care.
AB  - BACKGROUND: Chronic fatigue is a common condition, frequently presenting in
      primary care. The aim of this study was to compare the cost-effectiveness of
      cognitive behavioural therapy (CBT) and graded exercise therapy (GET), and to
      compare therapy with usual care plus a self-help booklet (BUC). METHOD: Patients
      drawn from general practices in South East England were randomized to CBT or GET.
      The therapy groups were then compared to a group receiving BUC recruited after
      the randomized phase. The main outcome measure was clinically significant
      improvements in fatigue. Cost-effectiveness was assessed using the net-benefit
      approach and cost-effectiveness acceptability curves. RESULTS: Costs were
      available for 132 patients, and cost-effectiveness results for 130. Costs were
      dominated by informal care. There were no significant outcome or cost differences
      between the therapy groups. The combined therapy group had significantly better
      outcomes than the standard care group, and costs that were on average 149 pounds
      higher (a non-significant difference). Therapy would have an 81.9% chance of
      being cost-effective if society were willing to attach a value of around 500
      pounds to each four-point improvement in fatigue. CONCLUSION: The cost
      effectiveness of cognitive behavioural therapy and graded exercise were similar
      unless higher values were placed on outcomes, in which case CBT showed improved
      cost-effectiveness. The cost of providing therapy is higher than usual GP care
      plus a self-help booklet, but the outcome is better. The strength of this
      evidence is limited by the use of a non-randomized comparison. The cost
      effectiveness of therapy depends on how much society values reductions in
      fatigue.

PMID- 15554571
TI  - How accurate is recall of key symptoms of depression? A comparison of recall and
      longitudinal reports.
AB  - BACKGROUND: Assessment of lifetime major depression is usually made from a single
      interview. Most previous studies have investigated reliability. Comparison of
      recall of key symptoms and longitudinal reports shows the accuracy of recall, not
      just reliability. METHOD: At age 25, 1003 members of the Christchurch Health and
      Development Study cohort were asked to recall key symptoms of depression
      (sadness, loss of interest) up to age 21. This recall was compared with
      longitudinal reports at ages 15, 16, 18 and 21 years. Diagnosis was by DSM-III-R
      and DSM-IV criteria. RESULTS: Only 4% of those without previous reports recalled
      key symptoms. Of those with a diagnosis of depression up to age 21, 44% recalled
      a key symptom. Measures of severity of an episode (number of symptoms,
      impairment, duration, suicidally) and chronicity (years with a diagnosis, years
      with suicidal ideation) all strongly predicted recall. Current key symptoms
      increased recall, even after taking account of severity and chronicity. Being
      female and receiving treatment also predicted recall, although odds ratios were
      reduced to 1.6-1.7 when all other predictors were included. Comparison of risk
      factors for key symptoms showed similar results from longitudinal reports and
      recall. Sexual abuse, neuroticism, lack of parental attachment, gender, physical
      abuse and maternal depression were major risk factors in both sets of analyses.
      CONCLUSIONS: Forgetting of prior episodes of depression was common. Severity,
      chronicity, current depression, gender and treatment predicted recall. Lifetime
      prevalence based on recall will be markedly underestimated but the identification
      of major risk factors may be relatively little impaired.

PMID- 15554572
TI  - Validation of two survey diagnostic interviews among primary care attendees: a
      comparison of CIS-R and CIDI with SCAN ICD-10 diagnostic categories.
AB  - BACKGROUND: The most widely used survey measures in psychiatry, the Composite
      International Diagnostic Interview (CIDI) and the Clinical Interview Schedule
      Revised (CIS-R) have generated estimates of psychiatric morbidity that show
      considerable variation. Doubts have been raised regarding the validity of these
      structured lay interviewer assessments. There have been no direct comparisons of
      the performances of these instruments against a common, established criterion.
      METHOD: A total of 105 unselected primary care attendees were each interviewed
      with CIDI, CIS-R and SCAN in a single sitting with random order of
      administration. SCAN was administered by a SCAN trained psychiatrist, and CIDI
      and CIS-R by a public health doctor. Concordance was estimated for all ICD-10
      neurotic disorders. We assessed the overall discriminability of the CIS-R
      morbidity scale using a receiver operating characteristic (ROC) analysis.
      RESULTS: The concordance for CIDI for ICD-10 diagnoses was moderate to excellent
      (kappa= 0.58-0.97). Concordance for CIS-R ranged between poor and moderate (kappa
      = 0.10-0.65). The area under the ROC curve for the CIS-R morbidity scale with
      respect to any ICD-10 disorder [0.87 (95% CI 0.79-0-95)] indicated good overall
      discriminability, but poor sensitivity (44%) and high specificity (97%) at the
      usual CIS-R cut-point of 11/12. CONCLUSION: Among primary care attendees the CIDI
      is a highly valid assessment of common mental disorders, and the CIS-R is
      moderately valid. Previous studies may have underestimated validity. Against the
      criteria of all ICD-10 diagnoses (including less severe depressive and anxiety
      disorders) a much lower CIS-R cut-point is required than that which is usually
      advocated.

PMID- 15554573
TI  - Social adversity contributes to high morbidity in psychoses in immigrants--a
      national cohort study in two generations of Swedish residents.
AB  - BACKGROUND: Recent reports have indicated that immigrants have an elevated risk
      of schizophrenia as well as an increasing tendency for social exclusion. The aim
      of this study was to compare rates of schizophrenia and other psychoses in
      immigrants and their children of different ethnic groups with the majority
      population in Sweden in relation to social adversity. METHOD: The study
      population consists of a national cohort of 1.47 million adults (born 1929-1965)
      and 1.16 million children and youth (born 1968-1979) in family households from
      the national census of 1985. Multivariate Cox regression analyses was used to
      study hospital discharge data during 1991-2000 in relation to socio-economic
      household indicators from 1985 and 1990 (single adult household, adults having
      received social welfare, parental unemployment, urban residency, housing and
      socio-economic status). RESULTS: First as well as second generation immigrants
      had higher age and sex adjusted risk ratios for schizophrenia as well as for
      other psychoses (RRs 1.4-3.1 and 1.0-2.0 respectively) compared with the Swedish
      majority population. These risk ratios decreased considerably after adjusting for
      socio-economic indicators, for all groups, but particularly for the non-European
      immigrants. However, an elevated risk still remained in the Finnish and Eastern
      and Southern European study groups. CONCLUSIONS: A higher risk of schizophrenia
      and psychoses was found in two generations of immigrants of diverse ethnicity.
      The results indicate that social adversity contributes to the higher risk.

PMID- 15554574
TI  - Cluster analysis of key diagnostic variables from two independent samples of
      eating-disorder patients: evidence for a consistent pattern.
AB  - INTRODUCTION: The optimal classification of eating disorders has been a matter of
      considerable debate. The present paper tackles this issue using cluster analysis
      with large independent samples of eating-disorder patients. METHOD: Two samples
      of adult female patients from Sweden (n = 631) and England (n = 472) were
      classified on the basis of 10 key clinical variables of primary significance for
      diagnosing eating disorders. A separate series of cluster analyses were conducted
      on each sample. RESULTS: Results suggested that a three-cluster solution was
      optimal in both samples. The first cluster ('generalized eating disorder') was
      characterized by high levels of eating-disorder psychopathology on all variables
      except weight and menstrual functioning. The second cluster ('anorexics') was
      typified by low weight, amenorrhoea and the absence of binge eating, and seemed
      to correspond to the clinical picture of anorexia nervosa. The third cluster
      ('overeaters') was characterized by high weight and moderate levels of binge
      eating and compensatory behaviour. CONCLUSIONS: Results suggest that patients
      presenting to eating-disorder services in different countries have clinical
      features that fall into very similar patterns. These patterns resemble, but are
      not identical to, existing diagnostic categories.

PMID- 15554575
TI  - The associations between psychopathology and being overweight: a 20-year
      prospective study.
AB  - BACKGROUND: Psychiatric disorders and being overweight are major health problems
      with increasing prevalence. The purpose of this study was to test the hypothesis
      that being overweight is associated with a range of psychiatric conditions
      including minor and atypical depressive disorders, binge eating, and aggression.
      METHOD: Prospective community-based cohort study of young adults (n = 591)
      followed between ages 19 and 40. Information derived from six subsequent semi
      structured diagnostic interviews conducted by professionals over twenty years.
      Outcomes were being overweight [body-mass index (BMI)> 25] and average yearly
      weight change between ages 20 and 40 (BMI slope). RESULTS: 18.9 % of the
      participants were classified as being overweight. Being overweight turned out to
      be a stable trait: 77.7% of subjects were assigned to the same weight class at
      each interview. Atypical depression and binge eating were positively associated
      with both, increased weight gain and being overweight, while psychiatric
      conditions associated with aggressive behaviors (aggressive personality traits,
      sociopathy) were positively associated with being overweight, but were not
      related to the rate of weight change. Generalized anxiety disorder was negatively
      associated with overweight. These results persisted after controlling for
      substance use, levels of physical activity, demographic variables and family
      history of weight problems. CONCLUSIONS: This study shows relatively strong
      associations between eating-related and aggressive psychopathology and being
      overweight. Given the high prevalence rates of these conditions, this study
      encourages further research on the causality of psychopathology-overweight
      associations that might provide insight on novel preventive approaches for major
      health problems.

PMID- 15554576
TI  - Enlarged amygdala volume and reduced hippocampal volume in young women with major
      depression.
AB  - BACKGROUND: Evidence is increasing that amygdala and hippocampus show significant
      structural abnormalities in affective disorders. Two previous studies found
      enlarged amygdala size in subjects with recent-onset major depression. METHOD:
      Amygdala and hippocampal volumes were assessed in 17 young women with major
      depressive disorder and 17 healthy matched control subjects by use of three
      dimensional structural magnetic resonance imaging. The severity of depressive
      symptoms was assessed using the Hamilton Depression Scale and the Beck Depression
      Inventory. RESULTS: Compared with control subjects, depressive subjects had
      significantly larger (+13 %) amygdala volumes and significantly smaller (-12%)
      hippocampal volumes. Amygdala and hippocampal volumes were not significantly
      correlated with disorder-related variables. CONCLUSIONS: Our results are
      consistent with previous findings of structural abnormalities of amygdala and
      hippocampus in subjects with recent-onset major depression. It may be suggested
      that the size of the amygdala is enlarged in the first years of the disorder, and
      may decrease with prolonged disorder duration.

PMID- 15554577
TI  - Onset, timing and risk for depression and anxiety in family caregivers to heart
      transplant recipients.
AB  - BACKGROUND: Family members adopt key caregiving roles in the maintenance of
      transplant recipients' health. While the bulk of the caregiving literature
      suggests that rates of psychiatric disorder should be high in these caregivers,
      the potential benefits of transplantation may instead lead to less distress than
      in other caregiving situations. We examined prevalence and risk factors for
      depressive and anxiety-related disorders in caregivers throughout 3 years after
      their family member's heart transplant. METHOD: A total of 190 caregivers (97% of
      eligible respondents) were enrolled. They received psychiatric and psychosocial
      evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis
      determined cumulative rates of psychiatric disorders and the impact of potential
      risk factors. RESULTS: Rates of depressive and anxiety-related disorders met or
      exceeded other caregiver populations' rates. By 3 years post-transplant,
      cumulative onset rates were: Major Depressive Disorder (MDD), 31.6%, Adjustment
      disorders, 35.4% (29.4 % with anxious mood); Post-Traumatic Stress Disorder
      related to the transplant (PTSD-T), 22.5%, Generalized Anxiety Disorder, 7.3%,
      and any assessed disorder, 56.3%. PTSD-T occurred primarily during the first year
      post-transplant. Other disorders' rates increased over the entire study period.
      Risk for disorder was elevated by positive lifetime history of psychiatric
      disorder, greater post-transplant caregiving responsibilities, and a poorer
      relationship with the patient. Risk for MDD was further increased by caregiver
      unemployment, and risk for anxiety disorders was further increased by younger
      age, low sense of personal mastery, and high use of avoidance coping strategies.
      CONCLUSIONS: Transplantation is associated with costs and benefits for not only
      patients but family caregivers. Caregivers' risk for psychiatric illness should
      be considered when developing interventions to promote families' long-term
      adjustment to the transplant process.

PMID- 15554578
TI  - The risk factors for depression in first myocardial infarction patients.
AB  - BACKGROUND: Depression affects outcome following myocardial infarction but the
      risk factors for such depression have been little studied. This study considered
      whether the causes of depression occurring before and after myocardial infarction
      were similar to those of depression in the general population. METHOD:
      Consecutive patients admitted to hospital following their first myocardial
      infarction were interviewed with the Schedule for Clinical Assessment in
      Neuropsychiatry to detect psychiatric disorders and the Life Events and
      Difficulties Schedule to assess recent stress. Participants completed the
      Hospital Anxiety and Depression Scale (HADS) at entry to the study and 1 year
      later and the risk factors associated with a high score at both times were
      assessed. RESULTS: Of 314 (88% of eligible) patients who were recruited, 199
      (63%) were male and 63 (20%) had depressive disorders. Logistic regression
      identified the following as independently associated with depressive disorder
      that had been present for at least I month before the myocardial infarction:
      younger age, female sex, past psychiatric history, social isolation, having
      marked non-health difficulties and lack of a close confidant. At follow-up
      269/298 (90%) responded; of 189 participants not depressed at first assessment,
      39 (21%) became depressed by the 1 year follow-up. Logistic regression identified
      frequent angina as the only significant predictor of raised HADS scores at 12
      months. CONCLUSIONS: Depression developing during the year following myocardial
      infarction does not have the same risk factors as that which precedes myocardial
      infarction. Further clarification of the mechanisms linking depression to poor
      outcome may require separation consideration of pre- and post-myocardial
      infarction depression, and its risk factors.

PMID- 15554579
TI  - Theory of mind and mentalizing ability in antisocial personality disorders with
      and without psychopathy.
AB  - BACKGROUND: The literature on Theory of Mind (ToM) in antisocial samples is
      limited despite evidence that the neural substrates of theory of mind task
      involve the same circuits implicated in the pathogenesis of antisocial behaviour.
      METHOD: Eighty-nine male DSM-IV Antisocial Personality Disordered subjects
      (ASPDs) and 20 controls (matched for age and IQ) completed a battery of ToM
      tasks. The ASPD group was categorized into psychopathic and non-psychopathic
      groups based on a cut-off score of 18 on the Psychopathy Checklist: Screening
      Version. RESULTS: There were no significant group (control v. psychopath v. non
      psychopathic ASPD) differences on basic tests of ToM but both psychopathic and
      non-psychopathic ASPDs performed worse on subtle tests of mentalizing ability
      (faux pas tasks). ASPDs can detect and understand faux pas, but show an
      indifference to the impact of faux pas. On the face/eye task non-psychopathic
      ASPDs showed impairments in the recognition of basic emotions compared with
      controls and psychopathic ASPDs. For complex emotions, no significant group
      differences were detected largely due to task difficulty. CONCLUSIONS: The
      deficits in mentalizing ability in ASPD are subtle. For the majority of criminals
      with ASPD and psychopathy ToM abilities are relatively intact and may have an
      adaptive function in maintaining a criminal lifestyle. Our findings suggest the
      key deficits appear to relate more to their lack of concern about the impact on
      potential victims than the inability to take a victim perspective. The findings
      tentatively also suggest that ASPDs with neurotic features may be more impaired
      in mentalizing ability than their low anxious psychopathic counterparts.

PMID- 15554580
TI  - Abnormal response to metabolic stress in schizophrenia: marker of vulnerability
      or acquired sensitization?
AB  - BACKGROUND: Previous work suggests that individuals with schizophrenia display an
      altered homovanillic acid (HVA) response to metabolic stress. The present study
      replicated and extended this paradigm, including individuals with elevated
      genetic risk for schizophrenia. METHOD: Patients with psychosis (n = 50), non
      psychotic first-degree relatives of patients with psychosis (n = 51) and controls
      without psychosis (n = 50) underwent, in randomized order, double-blind
      administration of placebo and the glucose analogue 2-deoxy-D-glucose (2DG), which
      induces a mild, transient clinical state of glucoprivation. Plasma HVA and
      cortisol were assessed twice before the start of the 2DG/placebo infusion
      (baseline values), as well as four times post infusion. Data were analysed using
      multi-level random regression techniques. RESULTS: During the stress condition,
      significant increases in plasma HVA and cortisol were found. The increase in
      plasma HVA level during the stress condition was significantly stronger in
      patients than in controls, whereas this was not the case in relatives v.
      controls. The increase in plasma cortisol during the stress condition was
      significantly less in patients than controls, but no significant difference in
      the increase of plasma cortisol during stress was found in the comparison between
      relatives and controls. CONCLUSIONS: Patients with psychosis, but not their non
      psychotic first-degree relatives, show an altered neurobiological response to
      metabolic stress, suggesting that this dysregulation is not a genetically
      transmitted vulnerability, but an illness-related effect, possibly reflecting
      acquired sensitization of neuroendocrine systems by repeated environmental
      stressors or repeated stimulation with agonistic drugs.

PMID- 15554581
TI  - Specificity in the familial aggregation of overt and covert conduct disorder
      symptoms in a referred attention-deficit hyperactivity disorder sample.
AB  - BACKGROUND: To examine the familial associations of overt and covert antisocial
      behavior within the diagnosis of conduct disorder (CD) in families ascertained by
      referred children with attention-deficit hyperactivity disorder (ADHD), and to
      test if these familial associations differed between male and female probands.
      METHOD: Subjects were clinically-referred male and female ADHD children (n = 273)
      and their first-degree biological relatives (n = 807). Scores for overt and
      covert conduct problems were calculated by summing the DSM-III-R conduct disorder
      symptoms, as derived from structured diagnostic interviews. Familial aggregation
      analyses were conducted with multivariate regression modeling methodology.
      RESULTS: Proband overt scores significantly predicted the overt scores of their
      relatives, and proband covert scores significantly predicted the covert scores of
      their relatives. There was no evidence of covert symptom scores predicting overt
      scores or vice versa. There was some evidence that the aggregation of covert
      symptoms was stronger in the families of female probands. CONCLUSIONS: These
      results provide preliminary evidence that overt and covert conduct disorder
      symptoms are independently transmitted through families and may represent
      distinct familial syndromes.

PMID- 15554583
TI  - Findings of the POPMACT study.

PMID- 15554582
TI  - Influence of behavioral symptoms on rates of institutionalization for persons
      with Alzheimer's disease.
AB  - BACKGROUND: Recent studies indicate that behavioral symptoms may play a key role
      in decisions to institutionalize persons with Alzheimer's disease (AD), but the
      specific types of behavior that contribute to this increased risk have not been
      reliably identified. The relationship between behavioral symptoms and time to
      institutionalization was evaluated in a 4-year longitudinal study. METHOD: A
      total of 410 persons with the clinical diagnosis of AD completed annual clinical
      evaluations to assess cognitive impairment, functional limitations, delusions,
      hallucinations, depressive symptoms and physical aggression. Participation rates
      among survivors exceeded 90% for four follow-up evaluations with complete
      ascertainment of mortality and institutionalization. Time to institutionalization
      was evaluated using proportional hazards regression models in relation to time
      varying clinical features. RESULTS: In multivariate models, adjusted for
      demographic and social variables, four clinical features emerged as the
      predominant predictors of institutionalization: cognitive impairment level,
      physical aggression, hallucinations and depressive symptoms. These associations
      were virtually unchanged in analyses controlling for mortality. CONCLUSIONS:
      Specific behavioral symptoms are important independent risk factors for
      institutionalization in persons with AD. Because behavioral symptoms are
      susceptible to therapy, efforts to modify or prevent these symptoms deserve
      careful consideration as a means to delay institutionalization for persons with
      this disease.

PMID- 15554584
TI  - [Positron emission tomography (PET) imaging in head and neck cancer].
AB  - Positron Emission Tomography (PET) with 18F-Fluordeoxyglucose is a diagnostic
      imaging technique very useful in the management of head and neck cancer, better
      than anatomic imaging in most cases. PET shows higher diagnostic accuracy in the
      detection of local and regional tumor recurrences. PET is also indicated for the
      identification of unknown primary tumors when regional nodal metastasis is the
      presenting feature. The improved planning of radiation therapy with hybrid
      cameras PET-CT, the earlier diagnosis of post-radiotherapy residual disease and
      the possibility of monitoring the effects of chemotherapy makes PET imaging an
      important tool in evaluating tumor response to treatment.

PMID- 15554585
TI  - [Expression of annexins Al and A2 in the mucosa of the upper airdigestive tract].
AB  - INTRODUCTION: Annexins A1 and A2 have been related with the maintenance of tissue
      integrity. They have been identified in a wide variety of tissues, but little is
      known regarding their expression in upper the aerodigestive tract. The aim of
      this work is to describe the expression of these proteins in the mucosa of the
      upper aerodigestive tract. MATERIAL AND METHODS: Tissue samples from respiratory
      (nasal and laryngeal) and digestive (oral and pharyngeal) mucosa from non
      oncological patients were studied. Annexin A1 and A2 expression was determined by
      immunohistochemistry. RESULTS: Both annexins were expressed in the ciliated and
      in the stratified non-keratinized epithelia, but with a different pattern; ANXA1
      was expressed in the more differentiated cells whereas ANXA2 was expressed in the
      less differentiated ones (with the exception of the cilia of ciliated cells).
      CONCLUSION: Although annexins A1 and A2 are structurally and philogenetically
      related its expression pattern in the upper aerodigestive tract suggests that
      they have different functions.

PMID- 15554586
TI  - [Surgery for Atresia auris. Retrospective study of our results and correlation
      with Jahrsdoerfer prognostic criterium].
AB  - OBJECTIVES: The study goal was to evaluate the hearing follow up results in
      patients who underwent surgery for congenital aural atresia. We studied hearing
      results and correlated them with Jahrsdoerfer prognostic classification.
      Protocols management of unilateral and bilateral atresia auris are written
      considering to our results and other authors. METHODS: We conducted a
      retrospective review of 12 ears who underwent surgery for congenital aural
      atresia between 1989 and 2002. CT scan was used to evaluate Jahrsdoerfer
      prognostic classification and the correlation with the hearing results. RESULTS:
      There are significant statistical differences (p = 0.003) in air-bone gap closure
      before and after surgery, also a lineal significant correlation (p = 0.016)
      between Jahrsdoerfer prognostic classification and air-bone gap closure.
      CONCLUSION: Atresiaplasty surgery in individuals with congenital aural atresia
      can yield good hearing results in selected cases.

PMID- 15554587
TI  - [Clinical and performance results of functional endoscopic sinus surgery].
AB  - Our aim was to know the clinical performance and management results of Functional
      Endoscopic Sinus Surgery (FESS) in Spanish hospitals. We sent a survey on the use
      and results of FESS to 160 Spanish public hospitals in June of 2002, obtaining a
      response rate of 69%. 82.9% of the interviewed hospitals carried out FESS and
      17.1% of the remaining used the classic techniques of approaching the paranasal
      sinuses. The reported length of stay in hospital was 1.4 days for the FESS and
      2.4 for the traditional surgery. The surgical time was 15 minutes shorter for the
      CENS, and the rate of recurrence was 16% less than for the classic surgery. As
      years of experience in the practice of the CENS go by, the surgical times tend to
      decrease, that didn't happen with the rate of recurrence. In conclusion, we
      consider that FESS seems to improve the analyzed clinical performance and
      assistential results.

PMID- 15554588
TI  - [Quantitative spectral evaluation of vocal hypofunction].
AB  - The purpose of this study was to explore the interaction between voice
      asthenicity and the acoustic prediction of vocal hypofunction. One hundred and
      seven phonatory samples of Reinke's edema were categorized by listeners using
      GRBAS scale. Seven frequency and time domain parameters were used to predict
      perceptual severity of asthenicity. Logistic regresion analysis showed that a
      useful measure for the prediction of asthenicity was the loss of harmonic
      components in the middle and upper portion of the spectrum. A spectral
      classification of vocal hypofunction is proposed.

PMID- 15554589
TI  - [Percutanous dilation tracheotomy: our experience].
AB  - Percutaneous dilation Tracheotomy (PDT) is becoming a popular alternative to
      surgical tracheotomy. In our hospital, we recently adopted the use of the PDT in
      intensive care unit patients. OBJECTIVE: The objective [corrected] of this
      investigation is to characterize and quantify the rate of complications for PDT.
      MATERIALS AND METHODS: A prospective study of 60 PDT performed at different
      intesive care units, betweem September 2002 to July 2003. RESULTS: The
      intraoperative time for PDT was 8 minutes. Complications included 6 cases of mild
      intraoperative hemorrhage, 1 case of moderate intraoperative hemorrhage, 4 cases
      of mild postoperative hemorrhage and 1 case of subcutaneous emphysema.
      CONCLUSIONS: PDT is a good alternative to surgical tracheotomy and should be
      added to the otolaryngologists armamentarium of surgical airway procedures.

PMID- 15554591
TI  - [Idiopathic recurrent facial palsy].
AB  - We report a 34 year old female patient with six episodes of idiopathic right
      facial palsy, all of wich had total recovery. Idiopathic recurrent facial palsy
      is a rare entity, with a few cases in the literature. Recurrent facial palsy is
      usually in the setting of a family history and have both autosomal dominant and
      recessive inheritance or in the setting of hypertension and diabetes. A review of
      the literature does not report a previous case with six episodes.

PMID- 15554590
TI  - [CEA and Cyfra 21.1 study pre-treatment in 252 patients with head and neck
      carcinomas].
AB  - INTRODUCTION: Squamous cell carcinoma is the most frequent malignant tumor in the
      head and neck. As in most malignant tumors, the earlier the diagnosis, is made
      the longer the survivalis. Several molecules, including CEA and Cyfra 21.1, have
      been evaluated in an attempt to improve diagnosis and follow-up. OBJECTIVE: To
      investigate whether CEA and Cyfra 21.1 present pathological increased values
      prior to treatment, and to correlate tumor and patient characteristics with CEA
      and Cyfra 21.1 levels. MATERIAL AND METHODS: CEA and Cyfra 21.1 were measured pre
      treatment in sera of 252 patients treated for head and neck tumors from1999 to
      2003. RESULTS: Increases of CEA were detected in 23.6%, and increases of Cyfra
      21.1 in 19.1% of patients. Significative differences were found between the
      concentrations of Cyfra 21.1 related to the tumor stage, local extension,
      histological grade, and an increasing relation with age. No differences were
      found in relation to the primary tumor site. Regarding CEA, the only finding was
      an increased relation between concentrations of this marker and cigarette and
      alcohol habits. CONCLUSIONS: Cyfra 21.1 does not appear to be a good marker for
      tumoral screening of head and neck carcinomas. However, a good correlation was
      observed between sera concentrations of Cyfra 21.1, tumoral burden, and
      histological grade of the tumor, but this was not the case with CEA.

PMID- 15554592
TI  - [Nasal glioma].
AB  - Congenital midline nasal masses are rare and therefore easily misdiagnosed, but
      due to their possible complications, they require prompt diagnosis and
      management. In this article we review the three most common: dermoid cyst, glioma
      and encephalocele. Their tendency to have a similar presentation requires very
      good skills in taking the history and performing the physical exam as well as an
      adequate radiologic diagnosis including CT, MRI or both. It is very important
      that we always consider them to avoid taking a biopsy.

PMID- 15554593
TI  - Supporting smoking cessation in the medical specialist practice.
AB  - Although smoking cessation reduces the cardiovascular risk of smoking, why this
      is so is still uncertain. Nevertheless, because they are strongly and
      authoritatively involved in much of the serious health damage caused by smoking,
      medical specialists should do all they can to support their patients in stopping.
      This indispensable support can be improved, however, when specialists adapt more
      motivational and behaviour change promoting attitudes and communicative
      techniques.

PMID- 15554594
TI  - Use of intermediate cardiovascular endpoints in intervention studies: not as easy
      as it seems?
AB  - In the current issue of the Journal, Van den Berkmortel and coworkers' report on
      the effect of smoking cessation on cardiovascular risk reduction, as estimated by
      assessment of progression of carotid intima-media thickness (CIMT) and arterial
      stiffness. Much to the authors' surprise, their nonrandomised study among 33
      subjects who stopped smoking for at least two years, 55 persistent smokers and 50
      never-smokers showed no difference in rate of change in CIMT or arterial
      stiffness across the groups after two years of intervention. The intriguing
      question of the paper is whether the finding is true or may be attributed to
      potential flaws of the study, focussing on design and analytical procedures, the
      choice of the endpoint and the power of the study.

PMID- 15554595
TI  - Nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is an underdiagnosed liver disease
      characterised by steatosis, necroinflammation and fibrosis. This disease may
      eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly
      prevalent among obese individuals and among patients with diabetes mellitus type
      2. Nonalcoholic fatty liver (NAFL), a precursor of NASH, is the main cause of
      elevated serum liver enzymes among the general population. Insulin resistance is
      a major aetiological factor in NASH. Gradual weight loss, physical exercise and
      drugs that improve insulin sensitivity are potential therapies.

PMID- 15554596
TI  - Video capsule endoscopy: procedure, indications and diagnostic yield.
AB  - Video capsule endoscopy (VCE) is a new noninvasive imaging technique for the
      complete small bowel. It provides good to excellent visualisation of the mucosa
      of the small bowel and has a high diagnostic yield in selected patients with
      gastrointestinal blood loss of suspected small bowel origin and in patients with
      Crohn's disease. In comparison with small bowel X-ray and push enteroscopy,
      diagnostic yield appears to be superior. Although VCE is becoming increasingly
      popular, good studies on its clinical implications and application are only just
      emerging. In this paper we review the possibilities and limitations of clinical
      application of VCE.

PMID- 15554597
TI  - Increasing HDL cholesterol with extended-release nicotinic acid: from promise to
      practice.
AB  - BACKGROUND: The inverse relation between high-density lipoprotein cholesterol
      (HDL-C) and cardiovascular (CV) disease underscores the need for clinical
      evaluation of the effect of HDL-C increasing drugs on the prevalence of CV
      disease. METHODS: We review the efficacy of Niaspan on serum lipids and the
      occurrence of side effects either alone or in combination with statins, in
      randomised controlled trials (RCT) and comparative cohort trials (CCT). RESULTS:
      In four RCTs, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and
      lipoprotein(a) (Lp(a)) were decreased by 13, 26, and 17%, respectively, whereas
      HDL-C increased by 18%. In four CCTs a combination of Niaspan and statins showed
      an additional 22% reduction in LDL-C, 8% in TG and 6% in Lp(a) levels, compared
      with Niaspan monotherapy. Statin therapy had a minor additional effect of 1% on a
      total of 25% HDL-C increase during Niaspan treatment. Flushes occurred in 69% of
      the patients without any additional toxicity during combination therapy.
      CONCLUSION: Niaspan effectively raises HDL-C with concomitant beneficial effects
      on TG and LDL-C. Niaspan can be combined safely with statins and is also
      effective in patients with combined dyslipidaemia and type 2 diabetes mellitus.
      Trials on CV endpoints evaluating the effect of statins with Niaspan are urgently
      needed to settle whether this combination can confirm the high expectations for
      cardiovascular outcome.

PMID- 15554598
TI  - Two years of smoking cessation does not reduce arterial wall thickness and
      stiffness.
AB  - BACKGROUND: Smoking cessation rapidly reduces cardiovascular risk. The
      pathophysiological mechanisms involved are still being debated. We measured
      structural and functional arterial wall properties of the femoral and carotid
      arteries after smoking cessation to investigate their possible role in
      cardiovascular risk reduction. METHODS: Out of 127 smokers, 33 proved to stop
      smoking for two years. They were compared with 50 nonsmokers and 55 persistent
      smokers in a prospective study. Cross-sectional compliance and distensibility
      coefficients as well as intima-media thickness of both carotid arteries and of
      the right common femoral artery were measured ultrasonographically at baseline
      and 3, 6, 12 and 24 months after smoking cessation. The nonsmoking and persistent
      smokers group were measured twice at an interval of 24 months. RESULTS:
      Persistent smoking and two years of smoking cessation did not affect cross
      sectional compliance and distensibility coefficients. Although at baseline
      intimal-medial layers were thicker in smokers, the change over time in intima
      media thickness did not differ significantly between all three groups.
      CONCLUSION: Two years of smoking cessation was not accompanied by a slower
      progression or a regression in intima-media thickness nor by an improved cross
      sectional compliance or distensiblity coefficient. Nevertheless, smoking
      cessation should be recommended as it reduces cardiovascular risk rapidly after
      smoking cessation.

PMID- 15554599
TI  - FOLFOX3 in heavily pretreated patients with metastatic colorectal cancer.
AB  - BACKGROUND: The combination of oxaliplatin, 5-fluorouracil (5FU) and leucovorin
      (LV) has shown to be active and safe as first- or second-line chemotherapy for
      metastatic colorectal cancer (MCC). PATIENTS AND METHODS: The outcome of patients
      with MCC who had progressive disease after at least two lines of palliative
      chemotherapy and who were subsequently treated with oxaliplatin, 5FU and LV was
      reviewed. Patients received FOLFOX3 consisting of oxaliplatin (85 mg/m2) on day
      1, LV (500 mg/m2) as a two-hour infusion on days 1 and 2, and 5FU (3000 mg/m2) as
      a 46-hour infusion starting on day 1 in a cycle of two weeks. RESULTS: A total of
      28 patients were treated with a median number of 9.5 cycles (range 1-24) at a
      mean dose intensity of 73%. Six patients discontinued treatment due to toxicity,
      of whom three had sensory neuropathy grade 2. Six patients experienced grade 3
      toxicity: nausea (1), vomiting (1), diarrhoea (1), leucopenia (2) and
      thrombocytopenia (1); grade 4 toxicity was not observed. Twenty-five patients
      were evaluable for response, of whom four achieved a partial response (response
      rate 14%, based on intention to treat). The median progression-free survival was
      5.8 months and the median overall survival was 8.5 months. CONCLUSION: For
      heavily pretreated patients with MCC, the FOLFOX3 regimen is a fairly safe and
      effective treatment.

PMID- 15554600
TI  - No effect of folic acid on markers of endothelial dysfunction or inflammation in
      patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia.
AB  - BACKGROUND: Mild hyperhomocysteinaemia is a cardiovascular risk factor in
      patients with type 2 diabetes mellitus. Homocysteine may exert its detrimental
      effects through induction of endothelial dysfunction and/or chronic inflammation.
      In this study, we examined the effects of homocysteine-lowering therapy with
      folic acid on biochemical markers of endothelial dysfunction and low-grade
      inflammation in patients with type 2 diabetes mellitus and mild
      hyperhomocysteinaemia (> or = 14 micromol/l). METHODS: In a randomised, double
      blind, controlled trial, patients were treated with folic acid 5 mg or placebo
      for six months. At 0 and 6 months, albuminuria, von Willebrand factor, soluble
      cellular adhesion molecules, C-reactive protein, interleukin-6 and tumour
      necrosis factor-alpha were determined. RESULTS: Forty-one patients completed the
      study (folic acid 23, placebo 18). Baseline hyperhomocysteinaemia (median 17
      micromol/l, range 14 to 30 micromol/l) was reduced by 29% in the folic-acid
      treated group, and remained unchanged in patients receiving placebo. On average,
      folic acid treatment did not significantly affect any of the endothelial (e.g.
      von Willebrand factor: difference folic acid minus placebo +1%, confidence
      interval -3 to +16%) or inflammation (e.g. C-reactive protein: difference folic
      acid minus placebo +13%, confidence interval -42 to +52%) markers studied.
      Multiple regression analyses without and with adjustment for baseline differences
      in cardiovascular disease and ethnicity confirmed these results. An apparent
      beneficial effect of folic acid on albuminuria in crude analysis was attenuated
      by multiple adjustment (difference folic acid minus placebo -35%, confidence
      interval -178 to +32%, p=0.08, adjusted 0.26). CONCLUSION: The data indicate
      that, in this group of patients with type 2 diabetes mellitus and mild
      hyperhomocysteinaemia, lowering homocysteine with folic acid for six months does
      not improve biochemical markers of endothelial dysfunction or low-grade
      inflammation.

PMID- 15554601
TI  - An unusual presentation and way to diagnose hepatocellular carcinoma.
AB  - A 67-year-old man with a history of chronic obstructive pulmonary disease (COPD)
      was admitted with acute progression of dyspnoea, productive cough, fever,
      elevated central venous pressure, oedema and liver enzyme abnormalities.
      Pneumonia with secondary right-sided congestive heart failure was considered.
      Additional abdominal ultrasound examination confirmed by a CT scan showed a mass
      in the inferior vena cava (VCI) extending into the right atrium. The central
      liver location and impaired haemostasis rendered liver biopsy impossible. An
      alternative approach was discussed and guided by two-dimensional transoesophageal
      electrocardiography accessing the right internal jugular vein, biopsies were
      taken from the atrial mass with histology suggesting the presence of a
      hepatocellular carcinoma as the cause of acute dyspnoea.

PMID- 15554602
TI  - Gynaecomastia: is one cause enough?
AB  - Gynaecomastia can be detected in between one-third and two-thirds of men. A wide
      variety of causes of gynaecomastia, some physiological, some very serious, have
      been identified. We present a case in which the cause of the gynaecomastia seemed
      obvious after history taking and physical examination but we finally ended up
      with a more complex combination of diagnoses. This case stresses the importance
      of combining history taking and physical examination with additional laboratory
      testing for the assessment of gynaecomastia.

PMID- 15554603
TI  - Recurrent splinter haemorrhages weeks after a tick bite.
AB  - A 52-year-old man developed fever, headache, tinnitus, and painful joints. He
      reported a tick bite contracted during a summer holiday in the Netherlands,
      followed by erythema on his left arm three weeks earlier. Initial treatment with
      doxycycline had failed and he had now developed signs of meningoencephalitis.
      Laboratory tests showed an increased white cell count (16.1 x 10(9)/1), and
      elevated ESR (51/1h).

PMID- 15554604
TI  - Clinicians' autonomy till the bitter end--can we learn from the extraordinary
      case of Harold Shipman?
AB  - Harold Shipman has attained the dubious reputation of being the greatest mass
      murderer of modern times. A specific feature of his murders was that these were
      committed during regular general practice care, over a period of 20 years. There
      are no grounds to assume that Shipman's case is unique in itself, or unique to
      British general practice and this paper analyses ways in which the medical
      profession can safeguard itself against future medical murderers.

PMID- 15554605
TI  - The role of knowledge translation for cancer control in Canada.
AB  - The definition and scope of cancer control has been evolving since its inception.
      The most recent model of cancer control in Canada has acknowledged the importance
      of knowledge translation to ensure that research results are implemented in
      practice and will be used to inform policy. However, without effort, the process
      of translation does not happen on a consistent basis. Knowledge translation
      focusses on improving the adoption of an innovation, e.g., research results. A
      number of health organizations in Canada have identified knowledge translation as
      an important activity and have begun to develop departments or initiatives
      dedicated to its achievement. As the emphasis in cancer control is on the
      application of knowledge, knowledge translation has a role to play in attaining
      the objectives of cancer control in Canada. It is an ideal time for the Canadian
      Strategy for Cancer Control and other Canadian cancer control initiatives to
      determine where they will locate knowledge translation in relation to their
      objectives.

PMID- 15554606
TI  - Occupational exposure to chemical and petrochemical industries and bladder cancer
      risk in four western Canadian provinces.
AB  - Occupational factors have been proposed to play a critical role in bladder
      cancer. This population-based case-control study was conducted to confirm the
      association between selected occupational and non-occupational risk factors and
      risk of bladder cancer using data collected from the four western Canadian
      provinces. Unconditional logistic regression analyses were based on 549
      histologically confirmed bladder cancer cases and 1099 controls. Bladder cancer
      risk was found to increase with increasing pack-years of cigarette smoking with
      an odds ratio (OR) in the highest quartile of 3.32 (95% confidence interval [CI],
      2.28-4.82). A dose-response relationship was demonstrated between bladder cancer
      and pack-years of smoking (p < 0.0001). A positive trend was observed with coffee
      consumption in men (p < 0.0001), with the highest risk in the highest category of
      exposure: drinkers of four cups or more per day had an OR of 1.77 (95% CI 1.11
      2.82). Increased bladder cancer risk was associated with self-reported exposure
      at work to several chemicals: asbestos (OR 1.69 [95% CI 1.07-2.65]); mineral,
      cutting or lubricating oil (1.64 [95% CI 1.06-2.55]); benzidine (2.20 [95% CI
      1.00-4.87]). The population attributable fraction (PAF) estimates were 51% for
      cigarette smoking, 17% for heavy coffee consumption, 10% for mineral, cutting or
      lubricating oil exposure, 6% for asbestos exposure, and 1% for benzidine
      exposure. Although self-reported chemical exposures have important limitations,
      the findings are suggestive of increased risk for several associations previously
      reported between chemical agents or industries and risk of bladder cancer.

PMID- 15554607
TI  - The occurrence of abruptio placentae in Canada: 1990 to 1997.
AB  - Abruptio placentae is a serious obstetric condition associated with an increased
      incidence of perinatal mortality and morbidity. Despite this, there is little
      information on the occurrence of abruptio placentae in Canada. The Discharge
      Abstract Database from the Canadian Institute for Health Information was used to
      identify a cohort of women who had singleton live or stillbirth deliveries in
      Canada between 1990 and 1997 (n = 2,162,815). Rates of abruptio placentae and
      abruptio placentae ending in stillbirth were examined by calendar year, province,
      maternal age and urban/rural status. There is a trend towards an increasing rate
      of abruptio placentae by year, from 10.9 (95 % confidence interval [CI] 10.5
      11.3) cases/1000 deliveries in 1990 to a high of 12.1 (95% CI 11.6-12.5)
      cases/1000 deliveries in 1996, while the rate ending in stillbirth remained
      relatively constant. The abruptio placentae rate was highest in mothers over 40
      years of age and the case-fatality rate highest in those under 20. These results
      provide a baseline reference for rates of abruptio placentae in Canada.

PMID- 15554608
TI  - Computer assisted telephone interviewing (CATI) for health surveys in public
      health surveillance: methodological issues and challenges ahead.
AB  - This article describes methodological issues, challenges, and a vision for using
      computer assisted telephone interviewing (CATI) in a comprehensive public health
      surveillance system in the 21st century. Methodological issues include funding of
      surveys, survey frequency, sample size considerations, response rates, and types
      of bias to be considered in questionnaire design. Challenges include the
      recognition of the merits and limitations of CATI, and the potential for greater
      use in surveillance of public health issues in health regions requiring rapid and
      regular data. The vision of a CATI survey-based, rapid, flexible, cost-effective
      public health surveillance system is described. It is concluded that further
      discussion and views on improvements with regard to CATI methodological and
      practical issues will help build a better CATI survey-based public health
      surveillance system for the future.

PMID- 15554609
TI  - Reliability of self-reports: data from the Canadian Multi-Centre Osteoporosis
      Study (CaMos).
AB  - Reliable questions enhance study design. We assessed the reliability of questions
      that gather demographic, sun exposure, reproductive history, and physical
      activity information. Subjects were participants in the Canadian Multicentre
      Osteoporosis Study (CaMos), a cohort study of Canadian adults recruited January
      1996 to September 1997 in nine cities, stratified by sex, age, and location.
      Following personal interviews, 367 subjects were re-administered part of the
      questionnaire by telephone. Reliability was assessed using kappa and intra-class
      correlation. Reliability was excellent for employment status, reproductive
      history, weight and height (0.91 to 0.97), not differing greatly when stratified
      by age group or sex. Physical activity and sun exposure were reported with fair
      to good reliability (0.44 to 0.58), except for moderate activity (kappa = 0.30,
      95% confidence interval 0.23, 0.37). Stratification by body mass index did not
      show significant differences. Many items can be reported reliably, especially
      those of height, weight, employment status and reproductive history, and, to a
      lesser extent, physical activity and sun exposure. Similar questions might be
      used reliably in future studies.

PMID- 15554610
TI  - Rates of carpal tunnel syndrome, epicondylitis, and rotator cuff claims in
      Ontario workers during 1997.
AB  - The primary objective of this research was the calculation of crude and specific
      rates of first-allowed, lost-time carpal tunnel syndrome (CTS), epicondylitis,
      and rotator cuff syndrome/tear (RCS/RCT) claims in Ontario workers during 1997. A
      secondary objective was to determine if results related to these diagnoses were
      consistent with findings for all cumulative trauma disorders affecting the
      specific part of upper extremity region. Rates were calculated by combining claim
      counts and population "at-risk" estimates derived from the Ontario Workplace
      Safety and Insurance Board databases and Canadian Labour Force Survey,
      respectively. The prevention index was used to prioritize occupations for
      intervention. Gender-specific rates declined as one moved proximally along the
      upper extremity. Similarly, female to male claim rate ratios declined from 1.61
      for CTS to 0.47 for RCS/RCT. Frequently occurring highest rate and prevention
      index occupational categories across gender and diagnoses included "textiles,
      furs & leathergoods" and "other machining occupations". Diagnosis-specific
      findings were consistent with previously reported part of upper extremity
      findings.

PMID- 15554611
TI  - The first sideways-bonded peroxo complex for a tetraaminecobalt(III) species.
AB  - Cobalt(II) salts react with H2O2 in the presence of 2 equiv of
      tetramethylethylenediamine (tmen) to produce a stable sideways bonded mononuclear
      peroxo complex [Co(tmen)2O2]ClO4 which has been characterized chemically and by a
      single crystal X-ray determination. This is the first such tetraaminecobalt(III)
      complex, indeed, the first for any tetraaminemetal ion complex. The mononuclear
      peroxo complex can also be synthesized by O2 2- anation of cis
      [Co(tmen)2(OH2)2]3+. This reaction is reversed in acid, and this offers the
      potential to develop Co(III) catalyzed oxidation reactions.

PMID- 15554612
TI  - Immobilization of phosphines on silica: identification of byproducts via 31P
      CP/MAS studies of model alkyl-, aryl-, and ethoxyphosphonium salts.
AB  - Immobilizing bifunctional phosphines with ethoxysilane groups on silica often
      leads predominantly, and sometimes quantitatively, to P(V) side products that
      occupy space on the surface but cannot bind metal complexes. Although this side
      reaction is well-known, and dreaded because it leads to leaching of adsorbed
      catalysts that are not bound covalently, the exact nature of the surface-bound
      side product was not yet known. With the help of polycrystalline model compounds
      of the types [R3PEt]+X- and [R3POEt]+X- (R=alkyl, aryl; X=Cl-, Br-, I-, BF4-) and
      their solid-state NMR characteristics [delta(31P), CSA], it is demonstrated that
      the side product is an ethylphosphonium salt bound to the surface by a siloxide
      anion, [R3PEt]+[Si-O]-.

PMID- 15554613
TI  - Multiple coordination geometries supported by methylene-linked guanidines.
AB  - The methylene-linked bicyclic guanidine based on the 1,3,4,6,7,8-hexahydro-2H
      pyrimido[1,2-a]pyrimidine (hppH) framework provides a versatile platform able to
      support trigonal-planar, tetrahedral, and square-planar metal centers.

PMID- 15554614
TI  - Facile formation of molybdenum(VI) monooxo aryloxides MoO(OAr)4-nCln from
      molybdenum dioxo dichloride.
AB  - Molybdenum monooxo compoundsMoO(OAr)4-nCln (n=0-2, Ar=2,6-Me2C6H3 or 2,6-i
      Pr2C6H3) have been synthesized starting from the dioxo precursor MoO2Cl2. The
      complexes are characterized spectroscopically and by X-ray diffraction. The
      formation mechanism likely involves phenol precoordination followed by addition
      across the Mo=O bond.

PMID- 15554615
TI  - The first, discrete Zn4 tetrahedron with a selenium atom in the center: x-ray
      structure and solution study of [Zn4(mu4-Se)[Se2P(OPr)2]6].
AB  - The first discrete, selenium-centered tetranuclear zinc cluster [Zn4(mu4
      Se)[Se2P(OPr)2]6] was isolated and characterized. The cluster consists of six
      edge-bridged dsep ligands with four zinc atoms in a slightly distorted
      tetrahedron and a mu4-Se atom in the center. In addition, 12 mu2-bridging
      selenium atoms form a Se12 icosahedron. From variable-temperature 31P NMR
      studies, it was observed that the cluster [Zn4(Se)[Se2P(OPr)2]6] is partly
      decomposed to [Zn[Se2P(OPr)2]2] and the monomeric species [Zn[Se2P(OPr)2]2] is
      further in equilibrium with its dimer [Zn[Se2P(OPr)2]2]2.

PMID- 15554616
TI  - Isomerization and oxygen atom transfer reactivity in oxo-Mo complexes of
      relevance to molybdoenzymes.
AB  - Both dioxo Mo(VI) and mono-oxo Mo(V) complexes of a sterically restrictive N2O
      heteroscorpionate ligand are found to exist as cis and trans isomers. The
      thermodynamically stable isomer differs for the two oxidation states, but in each
      case, we have isolated the kinetically labile isomer and followed its
      isomerization to the thermodynamically stable form. The Mo(VI) complex is more
      stable in the cis geometry and isomerizes more than 6 times faster than the Mo(V)
      complex, which prefers the trans geometry. In OAT reactions with PPh3, the trans
      isomer of the dioxo-Mo(VI) reacts approximately 20 times faster than the cis
      isomer. Thus, there are both oxidation state and donor atom dependent differences
      in isomeric stability and reactivity that could have significant functional
      implications for molybdoenzymes such as DMSO reductase.

PMID- 15554617
TI  - Superloading of tin ligands into rhodium and iridium carbonyl cluster complexes.
AB  - The reactions of Rh4(CO)12 and Ir4(CO)12 with Ph3SnH have yielded the new Rh-Sn
      and Ir-Sn cluster complexes M3(CO)6(mu-SnPh2)3(SnPh3)3, 1 (M=Rh) and 2 (M=Ir).
      Both compounds contain triangular M3 clusters with three bridging SnPh2 and three
      terminal SnPh3 ligands. The M-M bonds are unusually long. Molecular orbital
      calculations indicate that this is due to the importance of M-Sn bonding and weak
      direct M-M interactions. Reaction of 1 with Ph3SnH at reflux in 1,2
      dichlorobenzene solvent yielded the complex Rh3(CO)3(SnPh3)3(mu-SnPh2)3(mu3
      SnPh)2, 3, which contains eight tin ligands: three terminal SnPh3, three edge
      bridging SnPh2, and two triply bridging SnPh ligands.

PMID- 15554618
TI  - Assembly of positively charged porphyrins driven by metal ions: a novel polymeric
      arrangement of cationic metalloporphyrin.
AB  - Crystallization and crystal structure analysis of chlorohydrates of either tri-
      or tetracationic copper porphyrins, namely copper(5,10,15-tris(N-methyl
      pyridinium-4-yl)-20-pyridine-porphyrinato) (1) and copper(5,10,15,20-tetrakis(N
      methyl-pyridinium-4-yl)-porphyrinato), respectively, have been performed. Two
      crystalline forms, 2 and 3, of the latter have been obtained under different
      preparation conditions. A novel kind of slipped stack chains of these cationic
      porphyrins has been detected. The pronounced saddle conformation of the porphyrin
      reveals pi-like interactions between the peripheral pyrrole Cb-Cb- "double bond"
      and the metal center. DFT calculations on the isolated porphyrins clearly show
      the HOMO orbitals with the correct topology to yield a bonding interaction among
      the stacked porphyrin units. To our knowledge, a slipped stack chain of
      positively charged porphyrins has never been previously reported, if the
      arrangement of faced units of monocationic metalloporphyrins or phthalocyanins is
      excluded.

PMID- 15554619
TI  - Porphyrin supermolecules: synthesis and self-assembly features of zinc-5-(3'
      pyridyl)-10,15,20-tris(4'-hydroxyphenyl)porphyrin.
AB  - Targeted synthesis of the title compound, with one converging coordination site
      and three diverging H-bonding sites, has led to the formation of multiporphyrin
      oligomers by directed intermolecular coordination, without resorting to external
      auxiliaries. A uniquely structured cyclic tetraporphyrin supermolecule was
      detected in solution, isolated in the solid state, and characterized in detail by
      X-ray diffraction.

PMID- 15554620
TI  - Cobalt and manganese nets via their wires: facile transformation in metal
      diorganophosphates.
AB  - The manganese and cobalt complexes [M(dtbp)2]n (M=Mn, Co; dtbp=di-tert-butyl
      phosphate), which exist as one-dimensional molecular wires, transform to
      [M(dtbp)2(bpy)2.2H2O]n by the addition of 4,4-bipyridine (bpy) at room
      temperature; the latter compounds form noninterpenetrating rectangular grid
      structures.

PMID- 15554621
TI  - [Gd-AAZTA]-: a new structural entry for an improved generation of MRI contrast
      agents.
AB  - An innovative MRI contrast agent based on the unprecedented and easily obtained
      ligand AAZTA is described. The simple and straightforward synthesis of the
      ligand, together with the potentiometric and relaxometric behavior of the
      corresponding Gd(III) chelate, is reported. The complex [Gd(AAZTA)]- shows
      outstanding magnetic properties connected with high thermodynamic stability in
      aqueous solution and a nearly complete inertness toward the influence of
      bidentate endogenous anions, placing this compound as one of the most promising
      candidates for the development of high performance MRI contrast agents.

PMID- 15554622
TI  - Observation of an unprecedented Cu Bis-His site: crystal structure of the H129V
      mutant of nitrite reductase.
AB  - Copper nitrite reductases contain both an electron-transfer type 1 Cu site and a
      catalytic type 2 Cu site. We have mutated one of the type 2 copper ligating
      histidines to observe the effect on catalytic turnover. This mutation has created
      a unique site where Cu is ligated by 2 His Nepsilon2 atoms alone.

PMID- 15554623
TI  - Magnetic anisotropy of a high-spin octanuclear nickel(II) complex with a meso
      helicate core.
AB  - The octanickel(II) cluster 2b has been synthesized from the novel
      ferromagnetically coupled dinickel(II) metallacryptand 1b assembled from the m
      phenylene-bis(oxamate) ligand. Complex 2b exhibits a dimer-of-tetramers
      structure, with two oxamate-bridged propeller-shaped tetranuclear units connected
      through three meta-substituted phenylenediamidate bridges, giving a
      metallacryptand core of the meso-helicate type. Complex 2b behaves as a
      ferromagnetically coupled dimer of two S=2 Ni(II)4 units with appreciable
      magnetic anisotropy.

PMID- 15554624
TI  - Anion-templated synthesis of metallacages as a means for the colorimetric
      detection of chlorides.
AB  - In the presence of chloride or bromide in the appropriate mixture of solvents, 6
      equiv of nickel(II) and 8 equiv of Hatu [Hatu=H2NC(=NH)NHC(=S)NH2] assemble to
      yield the metallacages [Ni6(atu)8X][ClO4]3 (atu=deprotonated form of Hatu; X=Cl,
      5; Br, 6) where four "units" of the square-planar complex Ni(atu)2 are
      coordinated to two further nickel centers, forming an octahedral cage around an
      encapsulated chloride or bromide anion. Synthesis of the cages is highly
      dependent on the nature of the anions and the solvents used. In methanol, the
      cage only forms if chloride is present; in a mixture of acetone/methanol, the
      cage forms in the presence of either chloride or bromide. An interesting feature
      of the templation process is that there is a dramatic color change associated
      with assembly of the building blocks in the presence of the appropriate anion to
      yield the cages. This color change has been used as the basis for the
      colorimetric detection of chloride anions in methanol. The reaction of 4 equiv of
      nickel(II), 8 equiv of Hatu, and 2 equiv of platinum(II) has also been carried
      out, yielding the mixed-metal cage [Pt2Ni4(atu)8Cl][ClO4]3 (7a); the X-ray
      crystal structure of this compound is reported herein.

PMID- 15554625
TI  - Mixed valence Mn(II)/Mn(III) [3 x 3] grid complexes: structural, electrochemical,
      spectroscopic, and magnetic properties.
AB  - Mn(II)9 grid complexes with a [Mn9(mu-O)12] core, obtained by self-assembly of a
      series of tritopic picolinic dihydrazone ligands with Mn(II) salts, have been
      oxidized by both chemical and electrochemical methods to produce mixed oxidation
      state systems. Examples involving [Mn(III)3Mn(II)6] and [Mn(III)4Mn(II)5]
      combinations have been produced. Structures are reported for [Mn9(2poap
      2H)6](NO3)6.14H2O (1), [Mn9(2poap-2H)6](ClO4)10.10H2O (3), and [Mn9(Cl2poap
      2H)6](ClO4)9.14H2O.3CH3CN (10). Structural studies show distinct contraction of
      the corner grid sites on oxidation, with overall magnetic properties consistent
      with the resulting changes in electron distribution. Antiferromagnetic exchange
      in the outer ring of eight metal centers creates a ferrimagnetic subunit, which
      undergoes antiferromagnetic coupling to the central metal, leading to S=1/2 (3)
      and S2/2 (10) ground states. Two moderately intense absorptions are observed on
      oxidation of the Mn(II) grids in the visible and near-infrared (1000 nm, 700 nm),
      associated with charge transfer transitions (LMCT, IVCT respectively). Compound 1
      crystallized in the monoclinic system, space group P2 1/n, with a=21.308(2) A,
      b=23.611(2) A, c=32.178(3) A, beta=93.820(2) degrees . Compound 3 crystallized in
      the tetragonal system, space group I, with a=b=18.44410(10) A, c = 24.9935(3) A.
      Compound 10 crystallized in the triclinic system, space group P, with
      a=19.1150(10) A, b=19.7221(10) A, c=26.8334(14) A, alpha=74.7190(10) degrees,
      beta=77.6970(10) degrees, gamma=64.7770(10) degrees. The facile oxidation of the
      Mn(II)9 grids is highlighted in terms of their potential use as molecular based
      platforms for switching and data storage.

PMID- 15554626
TI  - Selective solid-liquid extraction of lithium halide salts using a ditopic
      macrobicyclic receptor.
AB  - A ditopic salt receptor that is known to bind and extract solid NaCl, KCl, NaBr,
      and KBr into organic solution as their contact ion pairs is now shown by NMR and
      X-ray crystallography to bind and extract solid LiCl and LiBr as water-separated
      ion pairs. The receptor can transport these salts from an aqueous phase through a
      liquid organic membrane with a cation selectivity of K+ > Na+ > Li+. However, the
      selectivity order is strongly reversed when the receptor extracts solid alkali
      metal chlorides and bromides into organic solution. For a three-component mixture
      of solid LiCl, NaCl, and KCl, the ratio of salts extracted and complexed to the
      receptor in CDCl3 was 94:4:2, respectively. The same strong lithium selectivity
      was also observed in the case of a three-component mixture of solid LiBr, NaBr,
      and KBr where the ratio of extracted salts was 92:5:3. This observation is
      attributed to the unusually high solubility of lithium salts in organic solvents.
      The study suggests that ditopic receptors with an ability to extract solid salts
      as associated ion pairs may have application in separation processes.

PMID- 15554627
TI  - Synthesis and characterization of Pd(II) Complexes with bis-pyridinium and
      isoquinolinium N-ylides: moderate C-H...O=C intramolecular hydrogen bonds as
      source of conformational preferences.
AB  - The bis(N-ylide) Pd(II) complexes cis-[PdX2[eta2-[C(H)NCxHy]2CO]] (X=I,
      NCxHy=NC5H5, 2a; X=Br, NCxHy=NC5H5 and NC5H3-2,3-Me2, 2c, isoquinolinium NC9H7,
      2d) have been prepared by reaction of the corresponding bis-pyridinium salts with
      Pd(OAc)2 (1:1 molar ratio). Compounds 2 react with AgClO4 and Tl(acac) (1:1:1
      molar ratio) to give the acetylacetonato derivatives [Pd(acac-O,O'[eta2
      [C(H)NCxHy]2CO]]ClO4 (3a, c, d). In compounds 2 and 3, the bis-ylide is bonded as
      a C,C-chelate ligand through the two ylidic Calpha atoms. The reaction is
      stereoselective, and only one diastereoisomer is observed (meso form, RS/SR). The
      origin of the observed stereoselectivity lies with the establishment of
      intramolecular C-H...O=C hydrogen bonds between the ortho protons of the pyridine
      or isoquinoline fragments and the carbonyl oxygen, as it has been shown by
      density functional theory (DFT) calculations (B3LYP level) and Bader analysis of
      the electron density on model pyridinium ylides. Despite the inherent weakness of
      the C-H...O=C bonds, the results show that in these N-ylides the hydrogen bonds
      are stronger than expected and should be classified as moderate H bonds.

PMID- 15554628
TI  - Why is Re-Re bond formation/cleavage in [Re(bpy)(CO)3]2 different from that in
      [Re(CO)5]2? Experimental and theoretical studies on the dimers and fragments.
AB  - The Re(NN)(CO)3(THF) (NN=bpy=2,2'-bipyridine or dmb=4,4'-dimethyl-2,2'
      bipyridine) radical, produced by homolysis of [Re(NN)(CO)3]2 in THF solution by
      visible irradiation, dimerizes with rate constants kd=20 +/- 3 and 11 +/- 4 M(-1)
      s(-1) for NN=dmb and bpy, respectively. The dimerization processes are strikingly
      slow compared to those of typical metal radicals including Re(CO)5 (kd
      approximately 10(9) M(-1) s(-1)). In order to explain such slow reactions, we
      have performed B3LYP hybrid DFT and fully ab initio RHF and MP2 calculations on
      several conformations of [Re(bpy)(CO)3]2 (cis, trans, skewed cis, skewed trans)
      and [Re(CO)5]2 (staggered) and on their constituent monomer radicals and anions.
      The calculations show that the most stable geometry of [Re(bpy)(CO)3]2 is skewed
      cis, and the experimental infrared spectrum and photochemical properties of the
      [Re(bpy)(CO)3]2 dimer are best described by the calculated properties of the
      skewed cis conformer in which there is no low-lying unoccupied orbital that is
      predominantly sigma(MM) in character. The Re(bpy)(CO)3(THF) ligand radical is
      more stable than the 5-coordinate "17-electron" metal radical, Re(bpy)(CO)3,
      suggesting that the extremely slow dimerization rate most likely arises from the
      solvent blocking the binding site (i.e., the estimated fraction of the five
      coordinate monomer is 1.6 x 10(-2)). Theoretical results are consistent with our
      experimental results that the dimerization process proceeds via the Re centered
      radical, which is involved in a pre-equilibrium favoring the ligand-centered
      radical. Furthermore, time-dependent DFT calculations on [Re(bpy)(CO)3]2 and
      [Re(bpy)(CO)3]- identify the origin of UV-vis absorption in THF.

PMID- 15554629
TI  - Oxidative verdoheme formation and stabilization by axial isocyanide ligation.
AB  - The effect of isocyanides as axial ligands on the formation and stability of
      verdoheme by oxidation has been examined. The reaction of [Fe(III)(OEPO)]2 with t
      butyl isocyanide under dioxygen-free conditions results in the formation of (t
      BuNC)2Fe(II)(OEPO*) with an electron paramagnetic resonance at g=2.009 with a
      peak-to-peak separation of 23.5 G at 4 K. (OEPO is the trianion of
      octaethyloxophlorin and OEPO* is the radical dianion obtained from OEPO by one
      electron oxidation.) Exposure of chloroform solutions of either (2,6
      xylylNC)2Fe(II)(OEPO*) or (t-BuNC)2Fe(II)(OEPO*) to dioxygen followed by the
      addition of ammonium hexafluorophosphate results in their transformation into the
      diamagnetic verdohemes, [(2,6-xylylNC)2Fe(II)(OEOP)](PF6) and [(t
      BuNC)2Fe(II)(OEOP)](PF6), yields 68 and 70%, respectively. (OEOP is the anion of
      octaethyl-5-oxaporphyrin.) The oxidation reactions of (2,6-xylylNC)2Fe(II)(OEPO*)
      and (t-BuNC)2Fe(II)(OEPO*) have also been monitored by 1H NMR spectroscopy. No
      resonances due to paramagnetic products could be detected, the reactions appear
      to result only in the formation of the diamagnetic verdohemes, and the products
      are not susceptible to further oxidation.

PMID- 15554630
TI  - Structure of YAG crystals doped/substituted with erbium and ytterbium.
AB  - Two series of yttrium aluminum garnets doped with erbium and ytterbium ions have
      been studied by single-crystal X-ray diffraction. The single crystals were
      obtained by the Czochralski method. The concentration of doping ions was
      established by the plasma emission spectroscopy method. For the Er series, it is
      equal to 23.4, 46.7, 72.5, and 100%, whereas, for Yb-doped YAGs, it equals 26.5,
      48.2, 75.9, and 100%. The results are supplemented by the data obtained for pure
      YAG. The X-ray data for all samples were collected at two temperatures: 295(2)
      and 102(2) K. Additionally, for YAGs doped with ca. 50% of doping ions, some more
      detailed temperature measurements were performed. Pure single crystals of ErAG
      and YbAG were also studied as a function of diffraction angles. Careful single
      crystal measurements utilizing a CCD diffractometer revealed the unit cell
      parameters, which slightly-but significantly-deviate from cubic symmetry. The
      average unit cell parameters change linearly with the amount of substituting Er
      and Yb cations, with two different slopes related to the ionic radii. Both of the
      dodecahedral distances depend linearly on the concentration of the substituting
      ions, but the longer dodecahedral distance also changes with temperature contrary
      to the shorter one. There is no correlation between the octahedral interatomic
      distance [Al(VI)...O] and the unit cell parameter or temperature; however, weak
      trends appear for the tetrahedral [Al(IV)...O] distance. Such weak trends are
      just the secondary consequences of the ion substitution taking place at the
      dodecahedral site. The dependences between the unit cell parameters and the
      concentration of doping ions allow us to establish concentrations of particular
      doping ions in mixed (Er, Yb) doped YAGs just on the basis of the measured unit
      cell parameters and knowledge of the amount of Y.

PMID- 15554631
TI  - Synthesis of a digermane-containing tricylic nonadecadienedione incorporating an
      equivalent of ring-opened THF.
AB  - The combination of 2 equiv of bis[bis(trimethylsilyl)amide]germylene (5) with 2
      equiv of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in tetrahydrofuran (THF)
      results in the ring-opening of 1 equiv of THF to form 2,2,8,8
      tetrakis(1,1,1,3,3,3-hexamethyl-disilazan-2-yl)-5,16-diphenyl-7,9,14-trioxa
      1,3,5,16,18,19-hexaaza-2,8-digerma-tricyclo[13.2.1.13,6]nonadeca-6(19),15(18)
      diene-4,17-dione (6). This fast and nearly quantitative reaction builds a 15
      membered ring from five different molecules. The new ring, structurally assigned
      by X-ray crystallography, contains a flexible methylene chain that moves rapidly
      on the NMR time scale.

PMID- 15554632
TI  - Macrocyclic and lantern complexes of palladium(II) with bis(amidopyridine)
      ligands: synthesis, structure, and host-guest chemistry.
AB  - The reactions of [PdCl2(NCPh)2] in a 1:1 ratio with the bis(amidopyridine)
      ligands LL=C6H3(5-R)(1,3-CONH-3-C5H4N)2 with R=H (1a) or R=t-Bu (1b) give the
      corresponding neutral dipalladium(II) macrocycles trans,trans-[Pd2Cl4(mu-LL)2],
      2a and 2b, which crystallize from dimethylformamide with one or two solvent
      molecules as macrocycle guests. The reaction of [PdCl2(NCPh)2] with LL in a 1:2
      ratio gave the cationic lantern complex [Pd2(mu-LL)4]Cl4, 3c (LL=1b), and the
      reaction in the presence of AgO2CCF3 gave the corresponding trifluoroacetate
      salts [Pd2(mu-LL)4](CF3CO2)4, 3a (LL=1a) and 3b (LL=1b). These lantern complexes
      exhibit a remarkable host-guest chemistry, as they can encapsulate cations,
      anions, and water molecules by interaction of the guest with either the
      electrophilic NH or the nucleophilic C=O substituents of the amide groups, which
      can be directed toward the center of the lantern through easy conformational
      change. The structures of several of these host-guest complexes were determined,
      and it was found that the cavity size and shape vary according to the ligand
      conformation, with Pd...Pd separations in the range from 9.45 to 11.95 A.
      Supramolecular ordering of the lanterns was observed in the solid state, through
      either hydrogen bonding or secondary bonding to the cationic palladium(II)
      centers. The selective inclusion by the lantern complexes of alkali metal ions in
      the sequence Na+ >> K+ >> Li+ was observed by ESI-MS.

PMID- 15554633
TI  - Steric and electronic control over the reactivity of a thiolate-ligated Fe(II)
      complex with dioxygen and superoxide: reversible mu-oxo dimer formation.
AB  - The reactivity between a thiolate-ligated five-coordinate complex
      [FeII(SMe2N4(tren))]+ (1) and dioxygen is examined in order to determine if O2
      activation, resembling that of the metalloenzyme cytochrome P450, can be promoted
      even when O2 binds cis, as opposed to trans, to a thiolate. Previous work in our
      group showed that [FeII(SMe2N4(tren))]+ (1) reacts readily with superoxide (O2-)
      in the presence of a proton source to afford H2O2 via an Fe(III)-OOH
      intermediate, thus providing a biomimetic model for the metalloenzyme superoxide
      reductase (SOR). Addition of O2 to 1 affords binuclear mu-oxo-bridged
      [FeIII(SMe2N4(tren))]2(mu2-O)(PF6)2.3MeCN (3). At low temperatures, in protic
      solvents, an intermediate is detected, the details of which will be the subject
      of a separate paper. Although the thiolate ligand does not appear to perturb the
      metrical parameters of the unsupported mu-oxo bridge (Fe-O= 1.807(8) A, and Fe-O
      Fe= 155.3(5) degrees fall in the usual range), it decreases the magnetic coupling
      between the irons (J=-28 cm(-1)) and creates a rather basic oxo site. Protonation
      of this oxo using strong (HBF4, HCl) or weak (HOAc, NH4PF6, LutNHCl) acids
      results in bridge cleavage to cleanly afford the corresponding monomeric anion
      ligated (OAc- (6), or Cl- (7)) or solvent-ligated (MeCN (4)) derivatives.
      Addition of OH- converts [FeIII(SMe2N4(tren))(MeCN2+ (4) back to mu-oxo 3. Thus,
      mu-oxo bridge cleavage is reversible. The protonated mu-hydroxo-bridged
      intermediate is not observed. In an attempt to prevent mu-oxo dimer formation,
      and facilitate the observation of O2-bound intermediates, a bulkier tertiary
      amine ligand, tren-Et4= N-(2-amino-ethyl)-N-(2-diethylamino-ethyl)-N',N'-diethyl
      ethane-1,2-diamine, and the corresponding [FeII(SMe2N4(tren-Et4))]+ (5) complex
      was synthesized and structurally characterized. Steric repulsive interactions
      create unusually long FeII-N(3,4) amine bonds in 5 (mean distance=2.219(1) A).
      The [(tren-Et4)N4SMe2]1- ligand is unable to accommodate iron in the +3 oxidation
      state, and consequently, in contrast to most thiolate-ligated Fe(II) complexes,
      [FeII(SMe2N4(tren-Et4))]+ (5) does not readily react with O2. Oxidation of 5 is
      irreversible, and the potential (Epa=+410 mV (vs SCE)) is anodically shifted
      relative to 1 (E1/2=-100 mV (vs SCE)).

PMID- 15554634
TI  - Aqueous speciation studies of europium(III) phosphotungstate.
AB  - The incorporation of lanthanide ions into polyoxometalates may be a unique
      approach to generate new luminescent, magnetic, and catalytic functional
      materials. To realize these new applications of lanthanide polyoxometalates, it
      is imperative to understand the solution speciation chemistry and its impact on
      solid-state materials. In this study we find that the aqueous speciation of
      europium(III) and the trivacant polyoxometalate, PW9O34 9-, is a function of pH,
      countercation, and stoichiometry. For example, at low pH, the lacunary (PW11O39)7
      predominates and the 1:1 Eu(PW11O39)4-, 2, forms. As the pH is increased, the
      1:2 complex, Eu(PW11O39)2 11- species, 3, and
      (NH4)22[(Eu2PW10O38)4(W3O8(H2O)2(OH)4].44H2O, a Eu8 hydroxo/oxo cluster, 1, form.
      Countercations modulate this effect; large countercations, such as K+ and Cs+,
      promote the formation of species 3 and 1. Addition of Al(III) as a counterion
      results in low pH and formation of [Eu(H2O)3(alpha-2-P2W17O61)]2, 4, with Al(III)
      counterions bound to terminal W-O bonds. The four species observed in these
      speciation studies have been isolated, crystallized, and characterized by X-ray
      crystallography, solution multinuclear NMR spectroscopy, and other appropriate
      tech-niques. These species are 1, (NH4)22[(Eu2PW10O38)4(W3O8(H2O)2(OH)4].44H2O
      (P; a=20.2000(0), b=22.6951(6), c=25.3200(7) A; alpha=65.6760(10),
      beta=88.5240(10), gamma=86.0369(10) degrees; V=10550.0(5) A3; Z=2), 2,
      Al(H3O)[Eu(H2O)2PW11O34].20H2O (P, a=11.4280(23), b=11.5930(23), c=19.754(4) A;
      alpha=103.66(3), beta=95.29(3), gamma=102.31(3) degrees; V =2456.4(9) A3; Z=2),
      3, Cs11Eu(PW11O34)2.28H2O (P; a=12.8663(14), b=19.8235(22), c=21.7060(23) A;
      alpha=114.57(0), beta=91.86(0), gamma=102.91(0) degrees ; V=4858.3(9) A3; Z=2),
      4, Al2(H3O)8[Eu(H2O)3(alpha-2-P2W17O61)]2.29H2O (P; a=12.649(6), b=16.230(8),
      c=21.518(9) A; alpha=111.223(16), beta=94.182(18), gamma=107.581(17) degrees ;
      V=3842(3) A3; Z=1).

PMID- 15554635
TI  - Computational modeling of di-transition-metal-substituted gamma-keggin
      polyoxometalate anions. Structural refinement of the protonated divacant lacunary
      silicodecatungstate.
AB  - The B3LYP density functional method has been validated for the di-Mn-substituted
      gamma-Keggin polyoxometalate (POM) anion, [(SiO4)MnIII2(OH)2W10O32]4-, and for
      the divacant lacunary silicodecatungastate, gamma-[(SiO4)W10O32]8-. This approach
      was shown to adequately describe the geometries of [(SiO4)MnIII2(OH)2W10O32]4-
      and gamma-[(SiO4)W10O32]8. Three different geometrical models, "full", "medium",
      and "small", for Mn2-gamma-Keggin have also been validated. It was shown that the
      medium [(SiO4)MnIII2(OH)2W6O24H8]4- model, as well as small
      [(SiO4)MnIII2(OH)2W4O18H10]2- model, preserves structural features of the full
      system, [(SiO4)MnIII2(OH)2W10O32]4-. However, the small model distorts the charge
      distribution at the "active site" of the system and should be used with caution.
      The same computational approach was employed to elucidate the structure of the di
      Fe-substituted gamma-Keggin POM. The structure of the acidic (tetra-protonated
      form) of lacunary POM, gamma-[(SiO4)W10O32H4]4-, was shown to be gamma
      [(SiO4)W10O28(OH)4]4- with four terminal hydroxo ligands, rather than gamma
      [(SiO4)W10O30(H2O)2]4- with two aqua and two oxo(terminal) ligands as reported by
      Mizuno and co-workers (Science 2003, 300, 964). The observed and calculated
      asymmetry in the W-O(terminal) bond distances of gamma-[(SiO4)W10O32H4]4- is
      explained in terms of the existence of O1H1...O2H2 and O4H4...O3H3 hydrogen
      bonding patterns in the gamma-[(SiO4)W10O28(OH)4]4- structure.

PMID- 15554636
TI  - Homoleptic cobalt and copper phenolate A2[M(OAr)4] compounds: the effect of
      phenoxide fluorination.
AB  - Two series of homoleptic phenolate complexes with fluorinated aryloxide ligands
      A2[M(OAr)4] with M=Co2+ or Cu2+, OAr-=(OC6F5)- (OArF) or [3,5-OC6H3(CF3)2]-
      (OAr'), A+=K (18-crown-6)+, Tl+, Ph4P+, Et3HN+, or Me4N+ have been synthesized.
      Two related complexes with nonfluorinated phenoxide ligands have been synthesized
      and studied in comparison to the fluorinated aryloxides demonstrating the
      dramatic structural changes effected by modification of OPh to OAr(F). The
      compounds [K(18-crown-6)]2[Cu(OArF)4], 1a; [K(18-crown-6)]2[Cu(OAr')4], 1b;
      [Tl2Cu(OArF)4], 2a; [Tl2Cu(OAr')4], 2b; (Ph4P)2[Cu(OArF)4], 3;
      (nBu4N)2[Cu(OArF)4], 4; (HEt3N)2[Cu(OArF)4], 5; [K(18-crown-6)]2[Cu2(mu2
      OC6H5)2(OC6H5)4], 6; [K(18-crown-6)]2[Co(OArF)4], 7a; [(18-crown-6)]2[Co(OAr')4],
      7b; [Tl2Co(OArF)4], 8a; [Tl2Co(OAr')4], 8b; (Me4N)2[Co(OArF)4], 9;
      [Cp2Co]2[Co(OAr')4], 10; and [(18-crown-6)])[Co2(mu2-OC6H5)2(OC6H5)4], 11, have
      been characterized with UV-vis and multinuclear NMR spectroscopy and solution
      magnetic moment studies. Cyclic voltammetry was used to study 1a, 1b, 7a, and 7b.
      X-ray crystallography was used to characterize 1b, 3, 4, 5, 6, 7a, 7b, 10, and
      11. The related [MX4]2- compound (Ph4P)2[Co(OArF)2Cl2], 12, has also been
      synthesized and characterized spectroscopically, as well as with conductivity and
      single-crystal X-ray diffraction. Use of fluorinated aryloxides permits synthesis
      and isolation of the mononuclear, homoleptic phenolate anions in good yield
      without oligomerized side products. The reaction conditions that result in
      homoleptic 1a and 7a with OArF upon changing the ligand to OPh result in mu2-OPh
      bridging phenoxides and the dimeric complexes 6 and 11. The [M(OArF)4]2- and
      [M(OAr')4]2- anions in 1a, 1b, 3, 4, 5, 7a, 7b, 9, and 10 demonstrate that
      stable, isolable homoleptic phenolate anions do not need to be coordinatively or
      sterically saturated and can be achieved by increasing the electronegativity of
      the ligand.

PMID- 15554637
TI  - Ligand oxidations in high-spin nickel thiolate complexes and zinc analogues.
AB  - Oxidations of a trigonal-bipyramidal, high-spin Ni(II) dithiolate complex of a
      pentadentate, N3S2-donor ligand, N1,N9-bis(imino-2-mercaptopropane)-1,5,9
      triazanonane) nickel(II), and the structurally analogous Zn(II) complex, lead to
      oxidations of the ligand. Oxidation of the Ni(II) complex with I2 produces a
      novel Ni(II) macrocyclic cationic complex containing a monodentate disulfide
      ligand (2). Crystals of the I3- salt of the complex form in the triclinic space
      group P(1) with cell dimensions a=8.508(3) A, b=9.681(2) A, c=14.066(4) A, angles
      alpha=90.97(2) degrees , beta=91.61(3) degrees , gamma=90.83(2) degrees , and
      Z=2. The structure was refined to R=6.31% and Rw=16.63% (I > 2sigma(I)).
      Oxidation of the Ni(II) complex with O2 leads to the formation of a novel
      pentadentate bis-iminothiocarboxylate complex with trigonal-bipyramidal geometry
      (3). This neutral product crystallizes in the monoclinic space group P21/c with
      cell dimensions a=13.625(3) A, b=7.605(5) A, c=14.902(4) A, angles alpha=gamma=90
      degrees, beta=102.81(2) degrees , and Z=4. The structure was refined to R=7.18%
      and Rw=17.86% (I > 2sigma(I)). Oxidation of the Zn(II) dithiolate analogue with
      O2 leads to the formation of the Zn(II) complex of the pentadentate bis
      iminothiocarboxylate ligand. The neutral complex is isomorphous with the Ni(II)
      complex and crystallizes in the monoclinic space group P2(1)/c with cell
      dimensions a=13.8465(4) A, b=7.6453(2) A, c=15.0165(6) A, angles alpha=gamma=90
      degrees , beta=103.2140(11) degrees , and Z=4. The structure was refined to
      R=3.96% and Rw=9.45% (I > 2sigma(I)). Details of the crystal structures are
      reported. Kinetics of the O2 reactions show that the reactions of the Ni(II) and
      Zn(II) dithiolates follow the rate law, Rate=k2[1][O2], with k2=1.81 M(-1) s(-1)
      for the Ni(II) complex and k2=1.93 x 10(-2) M(-1) s(-1) for the Zn(II) complex.
      The O2 oxidation of the high-spin Ni(II) thiolate complex was found to follow a
      similar oxidation mechanism to those of low-spin Ni(II) complexes, which form
      transient persulfoxide intermediates that yield S-oxidation products. In the case
      of the high-spin system reported here, the transient persulfoxide intermediate
      gives rise to an alternative ligand oxidation product, a bis-iminothiocarboxylate
      complex, because of the reactivity of the ligand, which contains a methylene with
      acidic H atoms alpha to the thiolate sulfur. The proposed mechanism is supported
      by studies of the analogous Zn dithiolate complex, which gives rise to the
      analogous bis-iminothiocarboxylate product (5).

PMID- 15554638
TI  - Syntheses, structure, some band gaps, and electronic structures of CsLnZnTe3
      (Ln=La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Y).
AB  - Eleven new quaternary rare-earth tellurides, CsLnZnTe3 (Ln=La, Pr, Nd, Sm, Gd,
      Tb, Dy, Ho, Er, Tm, and Y), were prepared from solid-state reactions at 1123 K.
      These isostructural materials crystallize in the layered KZrCuS3 structure type
      in the orthorhombic space group Cmcm. The structure is composed of LnTe6
      octahedra and ZnTe4 tetrahedra that share edges to form [LnZnTe3] layers. These
      layers stack perpendicular to [010] and are separated by layers of face- and edge
      sharing CsTe8 bicapped trigonal prisms. There are no Te-Te bonds in the structure
      of these CsLnZnTe3 compounds so the formal oxidation states of Cs/Ln/Zn/Te are
      1+/3+/2+/2-. Optical band gaps of 2.13 eV for CsGdZnTe3 and 2.12 eV for CsTbZnTe3
      were deduced from single-crystal optical absorption measurements. A first
      principles calculation of the density of states and the frequency-dependent
      optical properties was performed on CsGdZnTe3. The calculated band gap of 2.1 eV
      is in good agreement with the experimental value. A quadratic fit for the
      lanthanide contraction of the Ln-Te distance is superior to a linear one if the
      closed-shell atom is included.

PMID- 15554639
TI  - Synthesis and characterization of nitrosyl diruthenium complexes. Interaction
      between NO and CO across the metal-metal bond.
AB  - Two neutral diruthenium complexes and one anionic diruthenium complex,
      Ru2(dpf)4(NO), Ru2(dpf)4(NO)2, and [Ru2(dpf)4(NO)]-, where dpf is
      diphenylformamidinate anion, were synthesized and characterized as to their
      electrochemical and spectroscopic properties. Two of the compounds, Ru2(dpf)4(NO)
      and Ru2(dpf)4(NO)2, were also structurally characterized. Ru2(dpf)4(NO) undergoes
      reversible one-electron reductions under N2 at E1/2=0.06 and -1.24 V in CH2Cl2,
      0.1 M TBABr. These processes are shifted to E1/2=0.18 and -0.78 V under CO due to
      the trans-coordination of a CO molecule which stabilizes the singly and doubly
      reduced forms of the metal-metal bonded complexes, thus leading to easier
      reductions. CO does not coordinate to Ru2(dpf)4(NO), but it does bind to the
      singly reduced species to generate [Ru2(dpf)4(NO)(CO)]- under a CO atmosphere in
      solution; characteristic NO and CO bands are seen for this compound at nuNO=1674
      cm(-1) and nuCO=1954 cm(-1). Ru2(dpf)4(NO)2 displays a reversible one-electron
      reduction at E1/2=-1.24 V versus SCE and an irreversible reduction at Epc=-1.96 V
      in CH2Cl2, 0.1 M TBAP under N2. There are also two reversible one-electron
      oxidations at E1/2=0.24 and 1.15 V. Spectroelectrochemical monitoring of the
      Ru2(dpf)4(NO)2 oxidation processes in a thin-layer cell shows only a single NO
      vibration for each electrogenerated product and nuNO is located at 1726
      (neutral), 1788 (singly oxidized), or 1834 (doubly oxidized) cm(-1). Finally, a
      labile CO complex, [Ru2(dpf)4(NO)(CO)]-, could be generated by passing CO into a
      solution of [Ru2(dpf)4(NO)]-. Formation of the mixed CO/NO adduct was confirmed
      by electrochemistry and infrared spectroscopy. Analysis of the NO and CO
      stretching vibration frequencies for [Ru2(dpf)4(NO)(CO)]- by in-situ FTIR
      spectroelectrochemistry and comparisons with data for Ru2(dpf)4(NO) and
      Ru2(dpf)4(CO) reveal the presence of a strong interaction between NO and CO
      across the Ru-Ru bond.

PMID- 15554640
TI  - Synthesis, characterization, and electrochemical relationships of dinuclear
      complexes of platinum(II) and platinum(III) containing ortho-metalated tertiary
      arsine ligands.
AB  - Reaction of 2-Li-4-MeC6H3AsPh2 with [PtCl2(SEt2)2] gives two isomeric dinuclear
      platinum(II) complexes, one containing a half-lantern structure with two
      chelating and two bridging C6H3-5-Me-2-AsPh2 ligands, [Pt2(kappa2As,C-C6H3-5-Me-2
      AsPh2)2(mu-kappaAs,kappaC-C6H3-5-Me-2-AsPh2)2], and the other, a full-lantern
      with four bridging C6H3-5-Me-2-AsPh2 ligands, [Pt2(mu-kappaAs,kappaC-C6H3-5-Me-2
      AsPh2)4]. The lantern structure of the latter is retained in the
      dihalodiplatinum(III) complexes that are formed by oxidative addition of
      chlorine, bromine, or iodine to the isomeric mixture. The dichloro derivative
      undergoes metathesis reactions with silver or sodium salts, yielding the
      corresponding cyano, thiocyanato, cyanato, and fluoro species. The structures of
      all complexes have been determined by single-crystal X-ray analysis. The
      oxidative addition products have Pt-Pt distances in the range 2.65-2.79 A (cf.
      2.89 A in the lantern diplatinum(II) structure), consistent with the presence of
      a Pt-Pt bond. Electrochemical data lead to the conclusion that an initial rapid
      one-electron process and subsequent chemical reactions produce the
      dihalodiplatinum(III) lantern structure when mixtures of the lantern and half
      lantern complexes are oxidized by halogens. The electrochemical data also explain
      why chemical reduction of the dihalodiplatinum(III) complex produces only the
      lantern diplatinum(II) complex.

PMID- 15554641
TI  - New family of lithium salts for highly conductive nonaqueous electrolytes.
AB  - New lithium salts of weakly coordinating anions were prepared by treating lithium
      imidazolates or LiN(CH3)2 with 2 equiv of BF(3). They are LiIm(BF3)2, Li 2
      MeIm(BF3)2, Li 4-MeIm(BF3)2, LiBenzIm(BF3)2, Li 2-iPrIm(BF3)2, and
      LiN(CH3)2(BF3)2 (Im=imidazolate, Me=methyl, iPr=isopropyl,
      BenzIm=benzoimidazolate). The salts were characterized by NMR spectroscopy and
      mass spectrometry. The structure of LiBenzIm(BF3)2 consists of a dimeric
      centrosymmetric unit with each lithium atom forming a bridge between the two
      anions through one fluorine contact to each anion. The structure of a hydrate of
      LiN(CH3)2(BF3)2 consists of an infinite chain in which each anion chelates two
      different lithium atoms through Li-F bonds. The conductivities of electrolyte
      solutions of these salts were measured and are discussed in terms of different
      ion-pairing modes determined from the solid-state structures, the anion's ability
      to distribute charge, and solution viscosity. Organic carbonate solutions of
      LiIm(BF3)2 partially disproportionate at 85 degrees C forming LiBF4,
      LiBF2[Im(BF3)]2, and Li[(BF3)ImBF2ImBF2Im(BF3)], reaching equilibrium by 3 months
      at 85 degrees C but not disproportionating at room temperature after 9 months. A
      mechanism for the formation of these disproportionation products is proposed. The
      lower conductivity of the 1 M LiIm(BF3)2 solution that has undergone
      disproportionation is attributed to the formation LiBF4, which is less
      conductive, and LiBF2[Im(BF3)]2 and Li[(BF3)ImBF2ImBF2Im(BF3)], which increase
      solution viscosity.

PMID- 15554642
TI  - Complexes having the fac-[M(CO)3]+ core (M=Tc, Re) useful in
      radiopharmaceuticals: X-ray and NMR structural characterization and density
      functional calculations of species containing two sp3 N donors and one sp3 O
      donor.
AB  - Radiopharmaceuticals containing the "fac-[M(CO)3]+ " core (M=99mTc, 186Re, or
      188Re) have potential as diagnostic or therapeutic agents. Complexes with this
      core with sp3 amine donors have received little attention. We have studied
      adducts formed by ENDACH2 (HO2CCH2NHCH2CH2NHCH2CO2H) and ENACH
      (NH2CH2CH2NHCH2CO2H). Re(CO)3(ENDACH)-A (1A) and Re(CO)3(ENDACH)-B (1B) isomers
      were obtained by the reaction of ENDACH2 with Re(CO)5Cl. Re(CO)3(ENAC) (2) was
      obtained by the reaction of ENACH with aqueous [Re(CO)3(H2O)3]+. From single
      crystal X-ray data, the three new neutral complexes, 1A, 1B, and 2, have a six
      coordinate, pseudo-octahedral Re center with facially coordinated carbonyl
      ligands. ENDACH- and ENAC- bind facially to Re through both amine nitrogens and
      one carboxyl oxygen, forming two five-membered chelate rings. The Re(CO)3(ENDACH)
      isomers have an uncoordinated, dangling -CH2CO2H group, which is an ideal
      coupling site for attachment to biomolecules. The isomers differ by the
      configuration of the NH center bearing this dangling group. The H atom of the
      amine (N2) is endo (near the carbonyl ligands in the basal plane) in 1A and exo
      (away from carbonyl ligands) in isomer 1B. Isomers reach equilibrium (1A:1B,
      70:30) after 3 days at high pH. Density functional structure optimizations were
      performed for isolated molecules of the type Tc(I)/Re(I)(CO)3(N2O):
      [Re(CO)3(NH3)2(H2O)]+, [Tc(CO)3(NH3)2(H2O)]+, [Re(CO)3(EN)(H2O)]+ (EN,
      ethylenediamine), [Tc(CO)3(EN)(H2O)]+, and various models for 1A, 1B, and 2. The
      computed structures are in good agreement with the X-ray structures. The
      theoretical and experimental Re-N bond distances usually agree within 0.045 A.
      The total electronic energy values for the computed 1A and 1B models differ by
      0.815 kcal mol(-1), giving an isomer ratio of 80:20, in good agreement with the
      1A/1B ratio (70:30) found.

PMID- 15554643
TI  - Synthesis and structure of nongeminally substituted cyclic phosphazenes with
      haloalkyl and thioester functional groups.
AB  - Nongeminally substituted cyclic phosphazenes with various haloalkyl substituents
      were prepared using deprotonation-substitution reactions at the methyl groups of
      the cis isomers of nongeminally substituted cis-[Me(Ph)P=N]3, 2. Treatment of 2
      with n-BuLi followed by reaction with organic halogenated reagents (RX=C2Cl6,
      BrC(O)CMe2Br, and ICH2COOEt) at low temperature afforded the various cyclic
      derivatives cis-[(XCH2)(Ph)PN]3 (3, X=Cl, 4, Br, and 5, I). The mono- and
      dibromoalkyl derivatives, cis-[Ph3(BrCH2)Me2P3N3], 6, and [Ph3(BrCH2)2MeP3N3], 7,
      were also isolated along with 4 when the electrophile was dibromoethane. Reaction
      of cis-[Ph(BrCH2)PN]3, 4, with KSC(O)Me gave cis-[Ph(MeC(O)SCH2)PN]3, 8. The
      structures of all the cis cyclic phosphazenes were determined by NMR spectroscopy
      and X-ray diffraction. All retained the basketlike shape with the hydrophobic
      phenyl groups opposite the haloalkyl groups on the P3N3 ring. Thermal analysis of
      the new cyclic trimers indicates that ring-opening polymerization does not occur.
      The melting points and the thermal stabilities of haloalkyl cyclophosphazenes
      were higher than those of the parent compound 2.

PMID- 15554644
TI  - Synthesis, structure, and magnetic properties of heterometallic dicyanamide
      bridged Cu-Na and Cu-Gd one-dimensional polymers.
AB  - The monometallic precursors L1Cu and L2Cu (L1H2 standing for 1,3-bis((3
      ethoxysalicylidene)amino) propane and L2H2 standing for 1,2-bis((3
      methoxysalicylidene)amino) ethane) react with sodium dicyanamide (dca) (NaN3C2),
      a mixture of gadolinium nitrate, and sodium dicyanamide to yield heterodinuclear
      L2CuNa(NCNCN) and L1CuGd(NO3)(NCNCN)2 entities. The structural determination
      shows that two Cu-Na entities are linked by dca with an original mu1,1
      coordination mode, evidenced here for the first time, to yield tetranuclear
      complexes. Two hydrogen bonds operate between the water molecule coordinated to
      one of the sodium ions and the free nitrogen atoms of two dca ligands, yielding
      infinite zigzag chains. The structural determination of the Cu-Gd entities
      indicates that they are held together by two dca ligands, bridging alternately Cu
      to Gd and Gd to Gd cations, in the more common mu1,5 mode to yield a one
      dimensional (1D) network. The dca ligands are not able to transmit interaction
      between the magnetically active centers in these chains, which are the unique
      example of structurally characterized Cu-Gd complexes involving dca ligands.

PMID- 15554645
TI  - A family of dioxo-molybdenum(VI) complexes of N2X heteroscorpionate ligands of
      relevance to molybdoenzymes.
AB  - Four new Mo(VI)-dioxo complexes of a family of N2X heteroscorpionate ligands are
      reported which, together with data already available for (TpR)-, provide a unique
      example of a comprehensive set of isostructural, isoelectronic complexes
      differing only in one biologically relevant donor atom. A study of these
      complexes allows for a direct comparison of structural, spectroscopic, and oxygen
      atom transfer reactivity properties of the Mo(VI)-dioxo center (of relevance to
      various families of molybdoenzymes) as a function of donor atom identity.

PMID- 15554646
TI  - Divalent germanium compound with a radical-anionic ligand: molecular structures
      of (dpp-BIAN)*- GeCl and its hydrochloration products [(dpp-BIAN)(H)2]*+ [GeCl3]-
      and [[(dpp-BIAN)(H)2*+]2(Cl-)]+ [GeCl3]- (dpp-BIAN=1,2-Bis[(2,6
      diisopropylphenyl)imino]acenaphthene).
AB  - The germanium(II) compound (dpp-BIAN)GeCl (1), which contains the radical anion
      of dpp-BIAN can be prepared either by reacting free dpp-BIAN ligand with 2 equiv
      of GeCl2(1,4-dioxane) in Et2O or by metathetical reaction of the sodium salt of
      dpp-BIAN with germanium dichloride in Et2O or benzene. The reaction of benzene
      solutions of 1 with 2 or 3 equiv of HCl led to protonation of the dpp-BIAN ligand
      affording [(dpp-BIAN)(H)2]*+[GeCl3]- (2) and [[(dpp-BIAN)(H)2*+]2(Cl-)]+ [GeCl3]-
      (3), which incorporate the radical cation of the protonated ligand. Compounds 1-3
      have been characterized by elemental analysis, IR, UV-vis, and electron spin
      resonance (ESR) spectroscopy. Molecular structures of 1-3 were determined by
      single-crystal X-ray diffraction. In molecule 1, the Ge atom is positioned at the
      apex of the slightly distorted trigonal pyramid. The Ge-N bond lengths in 1 are
      2.0058(19) and 2.004(2) A. The molecular structure of 2 consists of contact ions
      [(dpp-BIAN)(H)2]+ and [GeCl3]-. In the molecular structure of 3, two radical
      cations of [(dpp-BIAN)(H)2]+ are "coordinated" by the chlorine anion. The ESR
      signal of 1 indicates the presence of a dpp-BIAN radical anion and shows a
      hyperfine structure due to the coupling of an unpaired electron to 14N, 73Ge,
      35Cl, 37Cl, and 1H nuclei (AN=0.48 (2 N), AGe=0.96, ACl=0.78 (35Cl), ACl=0.65
      (37Cl), AH=0.11 (4 H) mT, g=2.0014). Both 2 and 3 reveal ESR signals of radical
      cation [(dpp-BIAN)(H)2]*+ (septet, AN=0.53, AH=0.48 mT, g=2.0031).

PMID- 15554647
TI  - Nickel(II)-phenoxyl radical complexes: structure-radical stability relationship.
AB  - Nickel(II) complexes of N3O-donor tripodal ligands, 2,4-di-tert-butyl-6-[([bis(2
      pyridyl)methyl]amino)methyl]phenol (HtbuL), 2,4-di-tert-butyl-6-[([(6-methyl-2
      pyridyl)methyl](2-pyridylmethyl)amino)methyl]phenol (HtbuLMepy), and 2,4-di-tert
      butyl-6-[([bis(6-methyl-2-pyridyl)methyl]amino)methyl]phenol (HtbuL(Mepy)2), were
      prepared, and [Ni(tbuL)Cl(H2O)] (1), [Ni(tbuLMepy)Cl] (2), and
      [Ni(tbuL(Mepy)2)Cl] (3) were structurally characterized by the X-ray diffraction
      method. Complexes 1 and 3 have a mononuclear structure with a coordinated
      phenolate moiety, while 2 has a dinuclear structure bridged by two chloride ions.
      The geometry of the Ni(II) center was found to be octahedral for 1 and 2 and 5
      coordinate trigonal bipyramidal for 3. Complexes 1-3 exhibited similar absorption
      spectra in CH3CN, indicating that they all have a mononuclear structure in
      solution. They were converted to the phenoxyl radicals upon oxidation with
      Ce(IV), giving a phenoxyl radical pi-pi transition band at 394-407 nm. ESR
      spectra at low temperature and resonance Raman spectra established that the
      radical species has a Ni(II)-phenoxyl radical bond. The cyclic voltammograms
      showed a quasi-reversible redox wave at E1/2=0.46-0.56 V (vs Ag/AgCl)
      corresponding to the formation of the phenoxyl radical, which displayed a first
      order decay with a half-life of 45 min at room temperature for 1 and 26 and 5.9
      min at -20 degrees C for 2 and 3, respectively. The radical stability increased
      with the donor ability of the N ligands.

PMID- 15554648
TI  - Rhenium(IV)-copper(II) heterobimetallic complexes with a bridge malonato ligand.
      Synthesis, crystal structure, and magnetic properties.
AB  - The Re(IV) complex [ReCl4(mal)]2-, in the form of two slightly different salts,
      (AsPh4)1.5(HNEt3)0.5[ReCl4(mal)] (1a) and (AsPh4)(HNEt3)[ReCl4(mal)] (1b), and
      the Re(IV)-Cu(II) bimetallic complexes [ReCl4(mu-mal)Cu(phen)2].CH3CN (2),
      [ReCl4(mu-mal)Cu(bpy)2] (3), and [ReCl4(mu-mal)Cu(terpy)] (4) (mal=malonate
      dianion, AsPh4=tetraphenylarsonium cation, HNEt3=triethylammonium cation,
      phen=1,10-phenanthroline, bpy=2,2'-bipyridine and terpy=2,2':6',2' '-terpyridine)
      have been synthesized and the structures of 1a, 1b, 2, and 3 determined by single
      crystal X-ray diffraction. The structures of 1a and 1b are made up of discrete
      [ReCl4(mal)]2- anions and AsPh4+ and HNEt3+ cations, held together by
      electrostatic forces and hydrogen bonds. The Re(IV) atom is surrounded by four
      chloride anions and a bidentate malonate group, in a distorted octahedral
      environment. The structure of 2 consist of neutral dinuclear units [ReCl4(mu
      mal)Cu(phen)2], with the metal ions united through a bridge carboxilato. The
      environment of Re(IV) is nearly identical to that in the mononuclear complex, and
      Cu(II) is five coordinate, being surrounded by four nitrogen atoms of two
      bidentate phen ligands and one oxygen atom of the malonato ligand. In 3, there
      are also dinuclear units, [ReCl4(mu-mal)Cu(bpy)2], but the Cu(II) ions complete a
      distorted octahedral coordination by binding with the free malonato oxygen atom
      of a neighbor unit, resulting in an infinite chain. The magnetic properties of 1
      4 were also investigated in the temperature range 2.0-300 K. The magnetic
      behavior of 1a and 1b is as expected for a Re(IV) complex with a large value of
      the zero-field splitting (2D ca. 110 cm(-1)). For the bimetallic complexes, the
      magnetic coupling between Re(IV) and Cu(II) is antiferromagnetic in 2 (J=-0.39
      cm(-1)), ferromagnetic in 4 (J=+1.51 cm(-1)), and nearly negligible in 3 (J=-0.09
      cm(-1)).

PMID- 15554649
TI  - Influence of terpyridine as pi-acceptor ligand on the kinetics and mechanism of
      the reaction of NO with ruthenium(III) complexes.
AB  - The kinetics of the unusually fast reaction of cis- and trans
      [Ru(terpy)(NH3)2Cl]2+ (with respect to NH3; terpy=2,2':6',2"-terpyridine) with NO
      was studied in acidic aqueous solution. The multistep reaction pathway observed
      for both isomers includes a rapid and reversible formation of an intermediate
      Ru(III)-NO complex in the first reaction step, for which the rate and activation
      parameters are in good agreement with an associative substitution behavior of the
      Ru(III) center (cis isomer, k1=618 +/- 2 M(-1) s(-1), DeltaH(++) = 38 +/- 3 kJ
      mol(-1), DeltaS(++) = -63 +/- 8 J K(-1) mol(-1), DeltaV(++) = -17.5 +/- 0.8 cm3
      mol(-1); k -1 = 0.097 +/- 0.001 s(-1), DeltaH(++) = 27 +/- 8 kJ mol(-1),
      DeltaS(++) = -173 +/- 28 J K(-1) mol(-1), DeltaV(++) = -17.6 +/- 0.5 cm3 mol(-1);
      trans isomer, k1 = 1637 +/- 11 M(-1) s(-1), DeltaH(++) = 34 +/- 3 kJ mol(-1),
      DeltaS(++) = -69 +/-11 J K(-1) mol(-1), DeltaV(++) = -20 +/- 2 cm3 mol(-1); k(
      1)=0.47 +/- 0.08 s(-1), DeltaH(++)=39 +/- 5 kJ mol(-1), DeltaS(++) = -121 +/-18 J
      K(-1) mol(-1), DeltaV(++) = -18.5 +/- 0.4 cm3 mol(-1) at 25 degrees C). The
      subsequent electron transfer step to form Ru(II)-NO+ occurs spontaneously for the
      trans isomer, followed by a slow nitrosyl to nitrite conversion, whereas for the
      cis isomer the reduction of the Ru(III) center is induced by the coordination of
      an additional NO molecule (cis isomer, k2=51.3 +/- 0.3 M(-1) s(-1), DeltaH(++) =
      46 +/- 2 kJ mol(-1), DeltaS(++) = -69 +/- 5 J K(-1) mol(-1), DeltaV(++) = -22.6
      +/- 0.2 cm3 mol(-1) at 45 degrees C). The final reaction step involves a slow
      aquation process for both isomers, which is interpreted in terms of a
      dissociative substitution mechanism (cis isomer, DeltaV(++) = +23.5 +/- 1.2 cm3
      mol(-1); trans isomer, DeltaV(++) = +20.9 +/- 0.4 cm3 mol(-1) at 55 degrees C)
      that produces two different reaction products, viz. [Ru(terpy)(NH3)(H2O)NO]3+
      (product of the cis isomer) and trans-[Ru(terpy)(NH3)2(H2O)]2+. The pi-acceptor
      properties of the tridentate N-donor chelate (terpy) predominantly control the
      overall reaction pattern.

PMID- 15554650
TI  - Synthesis and characterization of a chromium(V) cis-dioxo bis(1,10
      phenanthroline) complex and crystal and molecular structures of its chromium(III)
      precursor.
AB  - The first structurally characterized Cr(V) dioxo complex, cis
      [CrV(O)2(phen)2](BF4) (2, phen=1,10-phenanthroline) has been synthesized by the
      oxidation of a related Cr(III) complex, cis-[Cr(III)(phen)2(OH2)2](NO3)3.2.5H2O
      (1, characterized by X-ray crystallography), with NaOCl in aqueous solutions in
      the presence of excess NaBF4, and its purity has been confirmed by electrospray
      mass spectrometry (ESMS), EPR spectroscopy, and analytical techniques. Previously
      reported methods for the generation of Cr(V)-phen complexes, such as the
      oxidation of 1 with PbO2 or PhIO, have been shown by ESMS to lead to mixtures of
      Cr(III), Cr(V), Cr(VI), and in some cases Cr(IV) species, 3. Species 3 was
      assigned as [CrIV(O)(OH)(phen)2]+, based on ESMS and X-ray absorption
      spectroscopy measurements. A distorted octahedral structure for 2 (CrO, 1.63 A;
      Cr-N, 2.04 and 2.16 A) was established by multiple-scattering (MS) modeling of
      XAFS spectra (solid, 10 K). The validity of the model was verified by a good
      agreement between the results of MS XAFS fitting and X-ray crystallography for 1
      (distorted octahedron; Cr-O, 1.95 A; Cr-N, 2.06 A). Unlike for the well-studied
      Cr(V) 2-hydroxycarboxylato complexes, 2 was equally or more stable in aqueous
      media (hours at pH=1-13 and 25 degrees C) compared with polar aprotic solvents. A
      stable Cr(III)-Cr(VI) dimer, [Cr(III)(Cr(VI)O4)(phen)2]+ (detected by ESMS), is
      formed during the decomposition of 2 in nonaqueous media. Comparative studies of
      the oxidation of 1 by NaOCl or PbO2 have shown that [Cr(V)(O)2(phen)2]+ was the
      active species responsible for the previously reported oxidative DNA damage,
      bacterial mutagenicity, and increased incidence of micronuclei in mammalian
      cells, caused by the oxidation products of 1 with PbO2. Efficient oxidation of 1
      to a genotoxic species, [Cr(V)(O)2(phen)2]+, in neutral aqueous media by a
      biological oxidant, hypochlorite, supports the hypothesis on a significant role
      of reoxidation of Cr(III) complexes, formed during the intracellular reduction of
      Cr(VI), in Cr(VI)-induced carcinogenicity. Similar oxidation reactions may
      contribute to the reported adverse effects of a popular nutritional supplement,
      Cr(III) picolinate.

PMID- 15554651
TI  - Computational insights into the acceptor chemistry of phosphenium cations.
AB  - Phosphines are traditionally considered as Lewis bases or ligands in transition
      metal and main group complexes. Despite their electron-rich (lone pair-bearing)
      nature, an extensive coordination chemistry for Lewis acidic phosphorus centers
      is being developed; such chemistry provides a new synthetic approach for
      phosphorus-element bond formation, leading to new types of structures and modes
      of bonding. Complexes of Ph2P+ with a variety of donor elements (P, N, C) give
      experimentally short donor-acceptor bond lengths, when compared to other cationic
      phosphorus Lewis acid complexes. We have calculated that the energy of the lowest
      unoccupied molecular orbital (LUMO) in Ph2P+ is lower than that of (Me2N)2P+,
      which partially explains the greater exothermicity of reactions of donors with
      the diaryl acceptor. Furthermore, the energies required to distort the
      diphenylphosphenium cation from its ground-state geometry are significantly
      smaller than those of the diamido cations and, thus, enhance the exothermicity of
      donor coordination. These computational data, in conjunction with evidence from
      experimental solid-state structures, indicate that Ph2P+ is a significantly
      better Lewis acid relative to the more common diaminophosphenium analogues
      (R2N)2P+ and are used to elucidate the nature of the bonding in donor-phosphenium
      complexes.

PMID- 15554652
TI  - Assembling novel heterotrimetallic Cu/Co/Ni and Cu/Co/Cd cores supported by
      diethanolamine ligand in one-pot reactions of zerovalent copper with metal salts.
AB  - The three novel heterotrimetallic complexes [Ni(H2L)2][CoCu(L)2(H2L)(NCS)]2(NCS)2
      (1), [Ni(H2L)2][CuCo(L)2(H2L)(NCS)]2Br2.2H2O (2), and
      [CuCoCd(H2L)2(L)2(NCS)Br2].CH3OH (3) have been prepared using zerovalent copper;
      cobalt thiocyanate; nickel thiocyanate (1), nickel bromide (2), or cadmium
      bromide (3); and methanol solutions of diethanolamine in air. The most prominent
      feature of the structures of 1 and 2 is the formation of the
      "pentanuclear"aggregate [[Ni(H2L)2][CoCu(L)2(H2L)(NCS)]2]2+ made up of two
      neutral [CoCu(L)2(H2L)(NCS)] units and the previously unknown cation [Ni(H2L)2]2+
      "glued together" by strong complementary hydrogen bonds. With Cd2+ instead of
      Ni2+, a different structure is obtained: the [CoCu(L)2(H2L)(NCS)] unit is now
      linked to the Cd center through coordination of the oxygens of L groups on the Co
      atom to form the discrete heterotrimetallic molecular species 3. Cryomagnetic
      measurements of the compounds show that, in all cases, the magnetic behavior is
      paramagnetic; the polycrystalline EPR spectra contain signals due to monomeric
      copper species only. At the same time, the EPR spectra of frozen DMF and methanol
      solutions of 1-3 reveal the presence of triplet-state species that can be
      generated only by a coupling of the Cu2+ centers within a dimer. The species
      responsible for the appearance of transitions within the triplet state are
      thought to be Cu(II) dimeric centers formed by aggregation of two [CuCo(H2L)(L)2]
      fragments of 1-3 present in solution. The residual monomeric spectra in the g
      approximately 2 region are indicative of the existence of an equilibrium in
      solution between the dimeric and monomeric Cu(II) centers in aggregated and free
      [CuCo(H2L)(L)2] fragments, respectively, with varying degrees of stability. The
      fragmentation process of 1-3 in solution was screened by electrospray ionization
      mass spectrometry.

PMID- 15554653
TI  - Mechanistic variations in the oxidation of Piloty's acid by metal complexes.
AB  - The reactions of N-hydroxybenzenesulfonamide (Piloty's acid, PA) with a variety
      of metal oxidants are reported. Either nitric oxide or nitrite is the final
      reaction product, along with benzenesulfinate and the reduced metal compound. The
      nitrogen product depends on the oxidation potential of the metal oxidant and its
      ability to further oxidize NO to nitrite. The observation and preliminary
      interpretation of unusual kinetic behavior of Piloty's acid as a reductant is
      also described. Analogues of PA were also prepared and found to show similar
      reactivity.

PMID- 15554654
TI  - Mimicking the two-dimensional spectrochemical series using density functional
      computations.
AB  - With tetragonal distortions of tetrahedral d2 complexes as examples, nonadditive
      and additive ligand fields are compared computationally, using Kohn-Sham density
      functional theory (KS-DFT) and ligand-field theory to obtain 45 linear,
      parametrical equations. For each complex, a "data" reduction from three
      nonadditive-field parameters to two parameters of the additive field occurs. The
      complexes V and CrX4- (where X=F, Cl, Br, I) provide the two-dimensional
      spectrochemical series of the sigma and pi AOM parameters, which are known
      semiempirically for the halide ligands. The same parametrical results can be
      obtained from the Kohn-Sham orbital energies of the "average of configuration"
      computation.

PMID- 15554655
TI  - Dirhenium paddlewheel compounds supported by N,N'-dialkylbenzamidinates:
      synthesis, structures, and photophysical properties.
AB  - Dirhenium(III,III) compounds Re2(DMBA)4Cl2 (1, DMBA=N,N'-dimethylbenzamidinate)
      and Re2(DEBA)4Cl2 (2, DEBA=N,N'-diethylbenzamidinate) were synthesized via molten
      reactions between Re2(OAc)4Cl2 and the corresponding amidine. Re2(DMBA)4(NO3)2
      (3) was obtained through reacting Re2(DMBA)4Cl2 with AgNO3. Single crystal X-ray
      diffraction studies revealed that the Re-Re distances in compounds 1-3 are
      2.212(1), 2.217(1), and 2.173(1) A, respectively, which are consistent with the
      presence of a Re-Re quadruple bond. Voltammetric studies revealed that compound 2
      exhibits two quasireversible couples, an oxidation and a reduction, and an
      irreversible reduction, while compound 1 displays irreversible couples at similar
      potentials. The three complexes exhibit 1deltadelta* absorption as a shoulder at
      approximately 440 nm (epsilon approximately 1500 M(-1) cm(-1)). Upon excitation
      of solid samples or CH2Cl2 solutions of 2 with visible light, emission is
      observed at 824 nm (77 K) and 833 nm (298 K), respectively. The luminescence is
      assigned as arising from the 3deltadelta* excited state.

PMID- 15554657
TI  - Molecules-in-molecule estimation of the extent of localization of Kekulean
      substructures in polycyclic aromatic hydrocarbons.
AB  - This article first revises graph-theoretical (local aromaticity and overall
      molecular) indices, introduced by M. Randic in 1975, for benzenoid hydrocarbons
      and somewhat improves them for computer enumeration. This goes beyond total
      Kekule structure enumeration, yielding an index calculation useful for the
      quantitative estimation of localization of different Kekulean substructures
      (including ethylene-, benzene-, annulene-, and radialene-units). This may be
      viewed as a "molecules-in molecule" approach to polycyclic aromatic hydrocarbons
      within the context of graph theoretical partitioning.

PMID- 15554658
TI  - Combining unsupervised and supervised artificial neural networks to
      predictaquatic toxicity.
AB  - Most quantitative structure-activity relationship (QSAR) models are linear
      relationships and significant for only a limited domain of compounds. Here we
      propose a data-driven approach with a flexible combination of unsupervised and
      supervised neural networks able to predict the toxicity of a large set of
      different chemicals while still respecting the QSAR postulates. Since QSAR is
      applicable only to similar compounds, which have similar biological and
      physicochemical properties, large numbers of compounds are clustered before
      building local models, and local models are ensembled to obtain the final result.
      The approach has been used to develop models to predict the fish toxicity of
      Pimephales promelas and Tetrahymena pyriformis, a protozoan.

PMID- 15554659
TI  - Representation of the molecular topology of cyclical structures by means of cycle
      graphs. 3. Hierarchical model of screening of chemical databases.
AB  - The increase in the size and complexity of chemical databases necessitates the
      proposal and development of efficient methods of classification and recovery of
      information, which supposes proposal of a model of classification of database
      records and the use of a compatible model of screening for inspection of clusters
      and recovery of the molecules that satisfy the search criterion. The cycle graphs
      model based on consideration of all the cycles and chains (and equivalent cycles
      and chains) present in the molecular structure has been proven appropriate for
      classification of chemical databases, giving rise to a generation of different
      classification levels depending on the structural elements (cycles and chains)
      that are considered. In this paper we propose a screening model, compatible with
      the cycle graphs model, based on a hierarchy of levels of abstraction. The set of
      molecules that satisfies a screening model (or selection criterion) diminishes as
      we advance in the hierarchy of levels of the model, which allows filtering of
      records and, therefore, an increase in the efficiency of the screening process.
      In the following work of this series we describe and validate the screening tool
      developed.

PMID- 15554660
TI  - Similarity to molecules in the training set is a good discriminator for
      prediction accuracy in QSAR.
AB  - How well can a QSAR model predict the activity of a molecule not in the training
      set used to create the model? A set of retrospective cross-validation experiments
      using 20 diverse in-house activity sets were done to find a good discriminator of
      prediction accuracy as measured by root-mean-square difference between observed
      and predicted activity. Among the measures we tested, two seem useful: the
      similarity of the molecule to be predicted to the nearest molecule in the
      training set and/or the number of neighbors in the training set, where neighbors
      are those more similar than a user-chosen cutoff. The molecules with the highest
      similarity and/or the most neighbors are the best-predicted. This trend holds
      true for narrow training sets and, to a lesser degree, for many diverse training
      sets and does not depend on which QSAR method or descriptor is used. One may
      define the similarity using a different descriptor than that used for the QSAR
      model. The similarity dependence for diverse training sets is somewhat
      unexpected. It appears to be greater for those data sets where the association of
      similar activities vs similar structures (as encoded in the Patterson plot) is
      stronger. We propose a way to estimate the reliability of the prediction of an
      arbitrary chemical structure on a given QSAR model, given the training set from
      which the model was derived.

PMID- 15554661
TI  - Accelerated K-means clustering in metric spaces.
AB  - The K-means method is a popular technique for clustering data into k-partitions.
      In the adaptive form of the algorithm, Lloyds method, an iterative procedure
      alternately assigns cluster membership based on a set of centroids and then
      redefines the centroids based on the computed cluster membership. The most time
      consuming part of this algorithm is the determination of which points being
      clustered belong to which cluster center. This paper discusses the use of the
      vantage-point tree as a method of more quickly assigning cluster membership when
      the points being clustered belong to intrinsically low- and medium-dimensional
      metric spaces. Results will be discussed from simulated data sets and real-world
      data in the clustering of molecular databases based upon physicochemical
      properties. Comparisons will be made to a highly optimized brute-force
      implementation of Lloyd's method and to other pruning strategies.

PMID- 15554662
TI  - Active learning with support vector machine applied to gene expression data for
      cancer classification.
AB  - There is growing interest in the application of machine learning techniques in
      bioinformatics. The supervised machine learning approach has been widely applied
      to bioinformatics and gained a lot of success in this research area. With this
      learning approach researchers first develop a large training set, which is a time
      consuming and costly process. Moreover, the proportion of the positive examples
      and negative examples in the training set may not represent the real-world data
      distribution, which causes concept drift. Active learning avoids these problems.
      Unlike most conventional learning methods where the training set used to derive
      the model remains static, the classifier can actively choose the training data
      and the size of training set increases. We introduced an algorithm for performing
      active learning with support vector machine and applied the algorithm to gene
      expression profiles of colon cancer, lung cancer, and prostate cancer samples. We
      compared the classification performance of active learning with that of passive
      learning. The results showed that employing the active learning method can
      achieve high accuracy and significantly reduce the need for labeled training
      instances. For lung cancer classification, to achieve 96% of the total positives,
      only 31 labeled examples were needed in active learning whereas in passive
      learning 174 labeled examples were required. That meant over 82% reduction was
      realized by active learning. In active learning the areas under the receiver
      operating characteristic (ROC) curves were over 0.81, while in passive learning
      the areas under the ROC curves were below 0.50.

PMID- 15554663
TI  - Expanded interaction fingerprint method for analyzing ligand binding modes in
      docking and structure-based drug design.
AB  - An expanded interaction fingerprint method has been developed for analyzing the
      binding modes of ligands in docking and structure-based design methods. Taking
      the basic premise of representing a ligand in terms of a binary string that
      denotes its interactions with a target protein, we have expanded the method to
      include additional interaction-specific information. By considering the hydrogen
      bonding strength and/or accessibility of the hydrogen bonding groups within a
      binding site as well as their geometric arrangement we aim to provide a better
      representation of a ligand-protein interaction. These expanded methods have been
      applied to the postprocessing of binding poses generated in a docking study for
      220 different proteins and to the analysis of ligands generated by an automated
      ligand-generation algorithm for the anthrax oedema factor. In the docking study,
      the application of the interaction fingerprint method as a postprocessing tool
      resulted in an increased success rate in identifying the crystallographic binding
      mode. In the analysis of the ligands generated for the anthrax oedema factor, the
      incorporation of additional interaction-specific information resulted in a more
      intuitive and comprehensive analysis of automated ligand-generation output.

PMID- 15554664
TI  - Computational models for the helix tilt angle.
AB  - The concept of hydrophobic imbalance and that of hydrophobic and hydrophilic
      centers are used along with side chain models in the computation of helix
      orientation and tilt angle in or near a membrane. Rotamer statistics are used to
      infer typical side chain positions and chain length for each amino acid, and the
      results are used in fast computation of helix orientation. Sliding windows are
      used to compute local tilt angles on long alpha-helices that defy idealized
      modeling and generate tilt angle profiles. Seven different procedures based on
      different formulas and hydrophobicity scales are used for comparison. These
      procedures generated very similar tilt angle profiles. These profiles provide
      insights into helix deformation, membrane destabilization, and similarity and
      differences between membrane proteins.

PMID- 15554665
TI  - Comparing ligand interactions with multiple receptors via serial docking.
AB  - Standard uses of ligand-receptor docking typically focus on the association of
      candidate ligands with a single targeted receptor, but actual applications
      increasingly require comparisons across multiple receptors. This study
      demonstrates that comparative docking to multiple receptors can help to select
      homology models for virtual compound screening and to discover ligands that bind
      to one set of receptors but not to another, potentially similar, set. A serial
      docking algorithm is furthermore described that reduces the computational costs
      of such calculations by testing compounds against a series of receptor structures
      and discarding a compound as soon as it fails to satisfy specified bind/no bind
      criteria for each receptor. The algorithm also realizes substantial efficiencies
      by taking advantage of the fact that a ligand typically binds in similar
      conformations to similar receptors. Thus, once detailed docking has been used to
      fit a ligand into the first of a series of similar receptors, much less extensive
      calculations can be used for the remaining structures.

PMID- 15554666
TI  - Ensemble methods for classification in cheminformatics.
AB  - We describe the application of ensemble methods to binary classification problems
      on two pharmaceutical compound data sets. Several variants of single and
      ensembles models of k-nearest neighbors classifiers, support vector machines
      (SVMs), and single ridge regression models are compared. All methods exhibit
      robust classification even when more features are given than observations. On two
      data sets dealing with specific properties of drug-like substances (cytochrome
      P450 inhibition and "Frequent Hitters", i.e., unspecific protein inhibition), we
      achieve classification rates above 90%. We are able to reduce the cross-validated
      misclassification rate for the Frequent Hitters problem by a factor of 2 compared
      to previous results obtained for the same data set with different modeling
      techniques.

PMID- 15554667
TI  - Quantitative prediction of logk of peptides in high-performance liquid
      chromatography based on molecular descriptors by using the heuristic method and
      support vector machine.
AB  - A new method support vector machine (SVM) and the heuristic method (HM) were used
      to develop the nonlinear and linear models between the capacity factor (logk) and
      seven molecular descriptors of 75 peptides for the first time. The molecular
      descriptors representing the structural features of the compounds only included
      the constitutional and topological descriptors, which can be obtained easily
      without optimizing the structure of the molecule. The seven molecular descriptors
      selected by the heuristic method in CODESSA were used as inputs for SVM. The
      results obtained by SVM were compared with those obtained by the heuristic
      method. The prediction result of the SVM model is better than that of heuristic
      method. For the test set, a predictive correlation coefficient R = 0.9801 and
      root-mean-square error of 0.1523 were obtained. The prediction results are in
      very good agreement with the experimental values. But the linear model of the
      heuristic method is easier to understand and ready to use for a chemist. This
      paper provided a new and effective method for predicting the chromatography
      retention of peptides and some insight into the structural features which are
      related to the capacity factor of peptides.

PMID- 15554668
TI  - Benzo[c]quinolizin-3-ones theoretical investigation: SAR analysis and application
      to nontested compounds.
AB  - We investigate with the use of theoretical methodologies the activity of a set of
      41 benzo[c]quinolizin-3-ones (BC3), some of them explored as selective inhibitors
      of the human 5alpha-reductase steroid. For the structure-activity study we have
      considered dividing the molecules into groups of tested and nontested compounds.
      Semiempirical calculations and pattern recognition methods such as Electronic
      Indices Methodology (EIM), Principal Components Analysis (PCA), Hierarchical
      Cluster Analysis (HCA), and K-Nearest Neighbors (KNN) have been applied to search
      for a correlation between experimental activity and theoretical descriptors. Our
      results show that it is possible to directly correlate some molecular quantum
      descriptors with BC3 biological activity. This information can be used in
      principle to identify active/inactive untested compounds and/or to design new
      active compounds.

PMID- 15554669
TI  - A new statistical approach to predicting aromatic hydroxylation sites. Comparison
      with model-based approaches.
AB  - A new approach is described that is able to predict the most probable metabolic
      sites on the basis of a statistical analysis of various metabolic transformations
      reported in the literature. The approach is applied to the prediction of aromatic
      hydroxylation sites for diverse sets of substrates. Training is performed using
      the aromatic hydroxylation reactions from the Metabolism database (Accelrys).
      Validation is carried out on heterogeneous sets of aromatic compounds reported in
      the Metabolite database (MDL). The average accuracy of prediction of
      experimentally observed hydroxylation sites estimated for 1552 substrates from
      Metabolite is 84.5%. The proposed approach is compared with two electronic models
      for P450 mediated aromatic hydroxylation: the oxenoid model using the atomic
      oxygen and the model using the methoxy radical as a model for the heme active
      oxygen species. For benzene derivatives, the proposed method is inferior to the
      oxenoid model and as accurate as the methoxy-radical model. For hetero- and
      polycyclic compounds, the oxenoid model is not applicable, and the statistical
      method is the most accurate. Broad applicability and high speed of calculations
      provide the basis for using the proposed statistical approach for high-throughput
      metabolism prediction in the early stages of drug discovery.

PMID- 15554670
TI  - Linear indices of the "molecular pseudograph's atom adjacency matrix":
      definition, significance-interpretation, and application to QSAR analysis of
      flavone derivatives as HIV-1 integrase inhibitors.
AB  - This report describes a new set of molecular descriptors of relevance to
      QSAR/QSPR studies and drug design, atom linear indices fk(xi). These atomic level
      chemical descriptors are based on the calculation of linear maps on Rn[fk(xi): Rn
      -> Rn] in canonical basis. In this context, the kth power of the molecular
      pseudograph's atom adjacency matrix [Mk(G)] denotes the matrix of fk(xi) with
      respect to the canonical basis. In addition, a local-fragment (atom-type)
      formalism was developed. The kth atom-type linear indices are calculated by
      summing the kth atom linear indices of all atoms of the same atom type in the
      molecules. Moreover, total (whole-molecule) linear indices are also proposed.
      This descriptor is a linear functional (linear form) on Rn. That is, the kth
      total linear indices is a linear map from Rn to the scalar R[ fk(x): Rn --> R].
      Thus, the kth total linear indices are calculated by summing the atom linear
      indices of all atoms in the molecule. The features of the kth total and local
      linear indices are illustrated by examples of various types of molecular
      structures, including chain-lengthening, branching, heteroatoms-content, and
      multiple bonds. Additionally, the linear independence of the local linear indices
      to other 0D, 1D, 2D, and 3D molecular descriptors is demonstrated by using
      principal component analysis for 42 very heterogeneous molecules. Much redundancy
      and overlapping was found among total linear indices and most of the other
      structural indices presently in use in the QSPR/QSAR practice. On the contrary,
      the information carried by atom-type linear indices was strikingly different from
      that codified in most of the 229 0D-3D molecular descriptors used in this study.
      It is concluded that the local linear indices are an independent indices
      containing important structural information to be used in QSPR/QSAR and drug
      design studies. In this sense, atom, atom-type, and total linear indices were
      used for the prediction of pIC50 values for the cleavage process of a set of
      flavone derivatives inhibitors of HIV-1 integrase. Quantitative models found are
      significant from a statistical point of view (R of 0.965, 0.902, and 0.927,
      respectively) and permit a clear interpretation of the studied properties in
      terms of the structural features of molecules. A LOO cross-validation procedure
      revealed that the regression models had a fairly good predictability (q2 of
      0.679, 0.543, and 0.721, respectively). The comparison with other approaches
      reveals good behavior of the method proposed. The approach described in this
      paper appears to be an excellent alternative or guides for discovery and
      optimization of new lead compounds.

PMID- 15554671
TI  - Optimized partition of minimum spanning tree for piecewise modeling by particle
      swarm algorithm. QSAR studies of antagonism of angiotensin II antagonists.
AB  - In quantitative structure-activity relationship (QSAR) modeling, when compounds
      in a training set exhibit a significant structural distinction between each
      other, in particular when chemicals of biological interest interacting on the
      receptor involve a different mechanism, it might be difficult to construct a
      single linear model for the whole population of compounds of interest with
      desired residuals. Developing a piecewise linear local model can be effective to
      circumvent the aforementioned problem. In this paper, piecewise modeling by the
      particle swarm optimization (PMPSO) approach is applied to QSAR study. The
      minimum spanning tree is used for clustering all compounds in the training set to
      form a tree, and the modified discrete PSO is applied to divide the tree to find
      satisfactory piecewise linear models. A new objective function is formulated for
      searching the appropriate piecewise linear models. The proposed PMPSO algorithm
      was used to predict the antagonism of angiotensin II. The results demonstrated
      that PMPSO is useful for improvement of the performance of regression models.

PMID- 15554672
TI  - Similarity search profiling reveals effects of fingerprint scaling in virtual
      screening.
AB  - Fingerprint scaling is a method to increase the performance of similarity search
      calculations. It is based on the detection of bit patterns in keyed fingerprints
      that are signatures of specific compound classes. Application of scaling factors
      to consensus bits that are mostly set on emphasizes signature bit patterns during
      similarity searching and has been shown to improve search results for different
      fingerprints. Similarity search profiling has recently been introduced as a
      method to analyze similarity search calculations. Profiles separately monitor
      correctly identified hits and other detected database compounds as a function of
      similarity threshold values and make it possible to estimate whether virtual
      screening calculations can be successful or to evaluate why they fail. This
      similarity search profile technique has been applied here to study fingerprint
      scaling in detail and better understand effects that are responsible for its
      performance. In particular, we have focused on the qualitative and quantitative
      analysis of similarity search profiles under scaling conditions. Therefore, we
      have carried out systematic similarity search calculations for 23 biological
      activity classes under scaling conditions over a wide range of scaling factors in
      a compound database containing approximately 1.3 million molecules and monitored
      these calculations in similarity search profiles. Analysis of these profiles
      confirmed increases in hit rates as a consequence of scaling and revealed that
      scaling influences similarity search calculations in different ways. Based on
      scaled similarity search profiles, compound sets could be divided into different
      categories. In a number of cases, increases in search performance under scaling
      conditions were due to a more significant relative increase in correctly
      identified hits than detected false-positives. This was also consistent with the
      finding that preferred similarity threshold values increased due to fingerprint
      scaling, which was well illustrated by similarity search profiling.

PMID- 15554673
TI  - Diagnosing anorexia based on partial least squares, back propagation neural
      network, and support vector machines.
AB  - Support vector machine (SVM), as a novel type of learning machine, for the first
      time, was used to develop a predictive model for early diagnosis of anorexia. It
      was based on the concentration of six elements (Zn, Fe, Mg, Cu, Ca, and Mn) and
      the age extracted from 90 cases. Compared with the results obtained from two
      other classifiers, partial least squares (PLS) and back-propagation neural
      network (BPNN), the SVM method exhibited the best whole performance. The
      accuracies for the test set by PLS, BPNN, and SVM methods were 52%, 65%, and 87%,
      respectively. Moreover, the models we proposed could also provide some insight
      into what factors were related to anorexia.

PMID- 15554674
TI  - Semiempirical quantum chemical method and artificial neural networks applied for
      lambdamax computation of some azo dyes.
AB  - The maximum absorption wavelengths of 31 azo dyes have been calculated by two
      comprehensive methods using the semiempirical quantum chemical method, PM3, and
      the weight decay based artificial neural network (WD-ANN) or the early stopping
      based artificial neural network (ES-ANN). The average absolute errors of WD-ANN
      and that of ES-ANN are 10.07 nm and 12.40 nm, respectively. These results are
      much better than the results using ZINDO/S with the default value (0.585) only.

PMID- 15554675
TI  - EChem++--an object-oriented problem solving environment for electrochemistry. 2.
      The kinetic facilities of Ecco--a compiler for (electro-)chemistry.
AB  - We describe a modeling software component Ecco, implemented in the C++
      programming language. It assists in the formulation of physicochemical systems
      including, in particular, electrochemical processes within general geometries.
      Ecco's kinetic part then translates any user defined reaction mechanism into an
      object-oriented representation and generates the according mathematical model
      equations. The input language, its grammar, the object-oriented design of Ecco,
      based on design patterns, and its integration into the open source software
      project EChem++ are discussed. Application Strategies are given.

PMID- 15554676
TI  - Use of classification regression tree in predicting oral absorption in humans.
AB  - The purpose of this study is to explore the use of classification regression
      trees (CART) in predicting, in the dose-independent range, the fraction dose
      absorbed in humans. Since the results from clinical formulations in humans were
      used for training the model, a hypothetical state of drug molecules already
      dissolved in the intestinal fluid was adopted. Therefore, the molecular
      attributes affecting dissolution were not considered in the model. As a result,
      the model projects the highest achievable fraction dose absorbed, providing a
      reference point for manipulating the formulations or solid states to optimize
      oral clinical efficacy. A set of approximately 1260 structures and their human
      oral pharmacokinetic data, including bioavailability and/or absorption and/or
      radio-labeled studies, were used, with 899 compounds as the training set and 362
      the test set. The numerical range of the fraction dose absorbed, 0 to 1, was
      divided into 6 classes with each class having a size of approximately 0.16. A set
      of 28 structural descriptors was used for modeling oral absorption without
      considering active transport. Then, a separate branch was created for modeling
      oral absorption involving active transport. The AAE of the training set was 0.12
      and those of five test sets ranged from 0.17 to 0.2. In terms of classification,
      two test sets of unpublished, proprietary compounds showed 79% to 86% prediction
      when the predicted values fallen within +/- one class of real values were
      considered predicted. Overall, the computational errors from all the test sets of
      diverse structures were similar and reasonably acceptable. As compared to
      artificial membranes for ranking drug absorption potential, prediction by the
      CART model is considered fast and reasonably accurate for accelerating drug
      discovery. One can not only improve continuously the accuracy of CART
      computations by expanding the chemical space of the training set but also
      calculate the statistical errors associated with individual decision paths
      resulting from the training set to determine whether to accept individual
      computations of any test sets.

PMID- 15554677
TI  - QSPR using MOLGEN-QSPR: the example of haloalkane boiling points.
AB  - MOLGEN-QSPR is a software newly developed for use in quantitative structure
      property relationships (QSPR) work. It allows to import, to manually edit, or to
      generate chemical structures, to detect duplicate structures, to import or to
      manually input property values, to calculate the values of a broad pool of
      molecular descriptors, to establish QSPR equations (models), and using such
      models to predict unknown property values. In connection with the molecule
      generator MOLGEN, MOLGEN-QSPR is able to predict property values for all
      compounds in a predetermined structure space (inverse QSPR). Some of the features
      of MOLGEN-QSPR are demonstrated on the example of haloalkane boiling points. The
      data basis used here is broader than in previous studies, and the models
      established are both more precise and simpler than those previously reported.

PMID- 15554678
TI  - How H-bonding affects aromaticity of the ring in variously substituted phenol
      complexes with bases. 4. Molecular geometry as a source of chemical information.
AB  - Aromaticity of the ring of variously substituted phenols in their H-bonded
      complexes with various bases was a subject of analysis based on 664 geometries
      retrieved from CSD and by use of the aromaticity index HOMA. GEO and EN, the
      components of the HOMA index, describing a decrease of aromaticity due to an
      increase of bond alternation (GEO term) and bond elongation (EN term), were also
      studied. There is an approximate monotonic dependence of HOMA and GEO on the H
      bond strength estimated by the C-O bond length of the hydroxyl group in phenols.

PMID- 15554679
TI  - Constructing optimum blood brain barrier QSAR models using a combination of 4D
      molecular similarity measures and cluster analysis.
AB  - A new method, using a combination of 4D-molecular similarity measures and cluster
      analysis to construct optimum QSAR models, is applied to a data set of 150
      chemically diverse compounds to build optimum blood-brain barrier (BBB)
      penetration models. The complete data set is divided into subsets based on 4D
      molecular similarity measures using cluster analysis. The compounds in each
      cluster subset are further divided into a training set and a test set. Predictive
      QASAR models are constructed for each cluster subset using the corresponding
      training sets. These QSAR models best predict test set compounds which are
      assigned to the same cluster subset, based on the 4D-molecular similarity
      measures, from which the models are derived. The results suggest that the
      specific properties governing blood-brain barrier permeability may vary across
      chemically diverse compounds. Partitioning compounds into chemically similar
      classes is essential to constructing predictive blood-brain barrier penetration
      models embedding the corresponding key physiochemical properties of a given
      chemical class.

PMID- 15554680
TI  - Quantitative structure-activity relationship for cyclic imide derivatives of
      protoporphyrinogen oxidase inhibitors: a study of quantum chemical descriptors
      from density functional theory.
AB  - This study examined the applicability of various density functional theory (DFT)
      based descriptors, such as energy gap (DeltaE) between the highest occupied
      molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO),
      weighted nucleophilic atomic frontier electron density (WNAFED, FNi), mean
      molecular polarizability (alpha), and net atomic charge (Qi), in quantitative
      structure-activity relationship (QSAR) studies on a class of important
      protoporphyrinogen oxidase (Protox) inhibitors including a series of cyclic imide
      derivatives with various heterocyclic rings and substituents. Our QSAR analysis
      using the quantum chemical descriptors calculated at the B3LYP/6-31G(d,p) level
      led to a useful explicit correlation relationship, i.e. pI50 = -5.7414 +
      0.1424alpha - 0.0003alpha2 - 0.4546FNC* + 0.2974QN** (n=26, R2=0.87), showing
      that descriptors mean molecular polarizability, alpha, and WNAFED FNC* of a
      critical carbon atom and net atomic charge (Qi) in the molecules are most likely
      responsible for the in vitro biological activity of cyclic imides. It has been
      shown that the use of the DFT-based quantum chemical descriptors indeed led to a
      better QSAR equation than that obtained from the use of the corresponding
      descriptors calculated at a semiempirical PM3 level. The present work
      demonstrates that the DFT-based quantum chemical descriptors are potentially
      useful in the future QSAR studies for quantitatively predicting biological
      activity, and, therefore, the DFT-based QSAR approach could be expected to help
      facilitate the design of additional substituted cyclic imide derivatives of
      Protox inhibitors with the potentially higher biological activity.

PMID- 15554681
TI  - New approach by Kriging models to problems in QSAR.
AB  - Most models in quantitative structure and activity relationship (QSAR) research,
      proposed by various techniques such as ordinary least squares regression,
      principal components regression, partial least squares regression, and
      multivariate adaptive regression splines, involve a linear parametric part and a
      random error part. The random errors in those models are assumed to be
      independently identical distributed. However, the independence assumption is not
      reasonable in many cases. Some dependence among errors should be considered just
      like Kriging. It has been successfully used in computer experiments for modeling.
      The aim of this paper is to apply Kriging models to QSAR. Our experiments show
      that the Kriging models can significantly improve the performances of the models
      obtained by many existing methods.

PMID- 15554682
TI  - An extensive test of 14 scoring functions using the PDBbind refined set of 800
      protein-ligand complexes.
AB  - Fourteen popular scoring functions, i.e., X-Score, DrugScore, five scoring
      functions in the Sybyl software (D-Score, PMF-Score, G-Score, ChemScore, and F
      Score), four scoring functions in the Cerius2 software (LigScore, PLP, PMF, and
      LUDI), two scoring functions in the GOLD program (GoldScore and ChemScore), and
      HINT, were tested on the refined set of the PDBbind database, a set of 800
      diverse protein-ligand complexes with high-resolution crystal structures and
      experimentally determined Ki or Kd values. The focus of our study was to assess
      the ability of these scoring functions to predict binding affinities based on the
      experimentally determined high-resolution crystal structures of proteins in
      complex with their ligands. The quantitative correlation between the binding
      scores produced by each scoring function and the known binding constants of the
      800 complexes was computed. X-Score, DrugScore, Sybyl::ChemScore, and
      Cerius2::PLP provided better correlations than the other scoring functions with
      standard deviations of 1.8-2.0 log units. These four scoring functions were also
      found to be robust enough to carry out computation directly on unaltered crystal
      structures. To examine how well scoring functions predict the binding affinities
      for ligands bound to the same target protein, the performance of these 14 scoring
      functions were evaluated on three subsets of protein-ligand complexes from the
      test set: HIV-1 protease complexes (82 entries), trypsin complexes (45 entries),
      and carbonic anhydrase II complexes (40 entries). Although the results for the
      HIV-1 protease subset are less than desirable, several scoring functions are able
      to satisfactorily predict the binding affinities for the trypsin and the carbonic
      anhydrase II subsets with standard deviation as low as 1.0 log unit
      (corresponding to 1.3-1.4 kcal/mol at room temperature). Our results demonstrate
      the strengths as well as the weaknesses of current scoring functions for binding
      affinity prediction.

PMID- 15554683
TI  - Binding of fatty acids to beta-cryptogein: quantitative structure-activity
      relationships and design of selective protein mutants.
AB  - Binding of fatty acids to cryptogein, the proteinaceous elicitor from
      Phytophthora, was studied by using molecular docking and quantitative structure
      activity relationships analysis. Fatty acids bind to the groove located inside
      the cavity of cryptogein. The structure-activity model was constructed for the
      set of 27 different saturated and unsaturated fatty acids explaining 87% (81%
      cross-validated) of the quantitative variance in their binding affinity. The
      difference in binding between saturated and unsaturated fatty acids was described
      in the model by three electronic descriptors: the energy of the lowest unoccupied
      molecular orbital, the energy of the highest occupied molecular orbital, and the
      heat of formation. The presence of double bonds in the ligand generally resulted
      in stronger binding. The difference in binding within the group of saturated
      fatty acids was explained by two steric descriptors, i.e., ellipsoidal volume and
      inertia moment of length, and one hydrophobicity descriptor, i.e., lipophility.
      The developed model predicted strong binding for two biologically important
      molecules, geranylgeranyol and farnesol playing an important role in plant
      signaling as lipid anchors of some membrane proteins. Elicitin mutants
      selectively binding only one type of ligand were designed for future experimental
      studies.

PMID- 15554684
TI  - Retrieval of crystallographically-derived molecular geometry information.
AB  - The crystallographically determined bond length, valence angle, and torsion angle
      information in the Cambridge Structural Database (CSD) has many uses. However,
      accessing it by means of conventional substructure searching requires nontrivial
      user intervention. In consequence, these valuable data have been underutilized
      and have not been directly accessible to client applications. The situation has
      been remedied by development of a new program (Mogul) for automated retrieval of
      molecular geometry data from the CSD. The program uses a system of keys to encode
      the chemical environments of fragments (bonds, valence angles, and acyclic
      torsions) from CSD structures. Fragments with identical keys are deemed to be
      chemically identical and are grouped together, and the distribution of the
      appropriate geometrical parameter (bond length, valence angle, or torsion angle)
      is computed and stored. Use of a search tree indexed on key values, together with
      a novel similarity calculation, then enables the distribution matching any given
      query fragment (or the distributions most closely matching, if an adequate exact
      match is unavailable) to be found easily and with no user intervention.
      Validation experiments indicate that, with rare exceptions, search results afford
      precise and unbiased estimates of molecular geometrical preferences. Such
      estimates may be used, for example, to validate the geometries of libraries of
      modeled molecules or of newly determined crystal structures or to assist
      structure solution from low-resolution (e.g. powder diffraction) X-ray data.

PMID- 15554685
TI  - The reduced graph descriptor in virtual screening and data-driven clustering of
      high-throughput screening data.
AB  - Virtual screening and high-throughput screening are two major components of lead
      discovery within the pharmaceutical industry. In this paper we describe
      improvements to previously published methods for similarity searching with
      reduced graphs, with a particular focus on ligand-based virtual screening, and
      describe a novel use of reduced graphs in the clustering of high-throughput
      screening data. Literature methods for reduced graph similarity searching encode
      the reduced graphs as binary fingerprints, which has a number of issues. In this
      paper we extend the definition of the reduced graph to include positively and
      negatively ionizable groups and introduce a new method for measuring the
      similarity of reduced graphs based on a weighted edit distance. Moving beyond
      simple similarity searching, we show how more flexible queries can be built using
      reduced graphs and describe a database system that allows iterative querying with
      multiple representations. Reduced graphs capture many important features of
      ligand-receptor interactions and, in conjunction with other whole molecule
      descriptors, provide an informative way to review HTS data. We describe a novel
      use of reduced graphs in this context, introducing a method we have termed data
      driven clustering, that identifies clusters of molecules represented by a
      particular whole molecule descriptor and enriched in active compounds.

PMID- 15554686
TI  - Design and characterization of libraries of molecular fragments for use in NMR
      screening against protein targets.
AB  - We have designed four generations of a low molecular weight fragment library for
      use in NMR-based screening against protein targets. The library initially
      contained 723 fragments which were selected manually from the Available Chemicals
      Directory. A series of in silico filters and property calculations were developed
      to automate the selection process, allowing a larger database of 1.79 M available
      compounds to be searched for a further 357 compounds that were added to the
      library. A kinase binding pharmacophore was then derived to select 174 kinase
      focused fragments. Finally, an additional 61 fragments were selected to increase
      the number of different pharmacophores represented within the library. All of the
      fragments added to the library passed quality checks to ensure they were suitable
      for the screening protocol, with appropriate solubility, purity, chemical
      stability, and unambiguous NMR spectrum. The successive generations of libraries
      have been characterized through analysis of structural properties (molecular
      weight, lipophilicity, polar surface area, number of rotatable bonds, and
      hydrogen-bonding potential) and by analyzing their pharmacophoric complexity.
      These calculations have been used to compare the fragment libraries with a drug
      like reference set of compounds and a set of molecules that bind to protein
      active sites. In addition, an analysis of the overall results of screening the
      library against the ATP binding site of two protein targets (HSP90 and CDK2)
      reveals different patterns of fragment binding, demonstrating that the approach
      can find selective compounds that discriminate between related binding sites.

PMID- 15554687
TI  - CoMFA 3D-QSAR analysis of HIV-1 RT nonnucleoside inhibitors, TIBO derivatives
      based on docking conformation and alignment.
AB  - HIV-1 RT is one of the key enzymes in the duplication of HIV-1. Inhibitors of HIV
      1 RT are classified as nonnucleoside RT inhibitors (NNRTIs) and nucleoside
      analogues. NNRTIs bind in a region not associated with the active site of the
      enzyme. Within the NNRTI category, there is a set of inhibitors commonly referred
      to as TIBO inhibitors. Fifty TIBO inhibitors were used in the work to build 3-D
      QSAR models. The two known crystal structures of complexes are used to
      investigate and validate the docking protocol. The results show that the docking
      simulations reproduce the crystal complexes very well with RMSDs of approximately
      1 A and approximately 0.6 A for 1REV and 1COU, respectively. The alignment of
      molecules and "active" conformation selection are the key to a successful 3D-QSAR
      model by CoMFA. The flexible docking (Autodock3) was used on determination of
      "active" conformation and molecular alignment, and CoMFA and CoMSIA were used to
      develop 3D-QSAR models of 50 TIBOs in the work. The 3D-QSAR models demonstrate a
      good ability to predict the activity of studied compounds (r2 = 0.972, 0.944, q2
      = 0.704, 0.776). It is shown that the steric and electrostatic properties
      predicted by CoMFA contours can be related to the binding structure of the
      complex. The results demonstrate that the combination of ligand-based and
      receptor-based modeling is a powerful approach to build 3D-QSAR models.

PMID- 15554688
TI  - Development of linear, ensemble, and nonlinear models for the prediction and
      interpretation of the biological activity of a set of PDGFR inhibitors.
AB  - A QSAR modeling study has been done with a set of 79 piperazyinylquinazoline
      analogues which exhibit PDGFR inhibition. Linear regression and nonlinear
      computational neural network models were developed. The regression model was
      developed with a focus on interpretative ability using a PLS technique. However,
      it also exhibits a good predictive ability after outlier removal. The nonlinear
      CNN model had superior predictive ability compared to the linear model with a
      training set error of 0.22 log(IC50) units (R2 = 0.93) and a prediction set error
      of 0.32 log(IC50) units (R2 = 0.61). A random forest model was also developed to
      provide an alternate measure of descriptor importance. This approach ranks
      descriptors, and its results confirm the importance of specific descriptors as
      characterized by the PLS technique. In addition the neural network model contains
      the two most important descriptors indicated by the random forest model.

PMID- 15554689
TI  - SitePrint: three-dimensional pharmacophore descriptors derived from protein
      binding sites for family based active site analysis, classification, and drug
      design.
AB  - Integrating biological and chemical information is one key task in drug
      discovery, and one approach to attaining this goal is via three-dimensional
      pharmacophore descriptors derived from protein binding sites. The SitePrint
      program generates, aligns, scores, and classifies three-dimensional pharmacophore
      descriptors, active site grids, and ligand surfaces. The descriptors are formed
      from molecular fragments that have been docked, minimized, filtered, and
      clustered in protein active sites. The descriptors have geometric coordinates
      derived from the fragment positions, and they capture the shape, electrostatics,
      locations, and angles of entry into pockets of the recognition sites: they also
      provide a direct link to databases of organic molecules. The descriptors have
      been shown to be robust with respect to small changes in protein structure
      observed when multiple compounds are cocrystallized in a protein. Five aligned
      thrombin cocrystals with an average core alpha-carbon RMSD of 0.7 A gave three
      dimensional pharmacophore descriptors with an average RMSD of 1.1 A. On a larger
      test set, alignment and scoring of the descriptors using clique-based alignment,
      and a best first search strategy with an adapted forward-looking Ullmann
      heuristic was able to select the global minimum three-dimensional alignment in
      twenty-nine out of thirty cases in less than one CPU second on a workstation. A
      protein family based analysis was then performed to demonstrate the usefulness of
      the method in producing a correlation of active site pharmacophore descriptors to
      protein function. Each protein in a test set of thirty was assigned membership to
      a family based on computed active site similarity to the following families:
      kinases, nuclear receptors, the aspartyl, cysteine, serine, and metallo
      proteases. This method of classifying proteins is complementary to approaches
      based on sequence or fold homology. The values within protein families for
      correctly assigning membership of a protein to a family ranged from 25% to 80%.

PMID- 15554690
TI  - REALISIS: a medicinal chemistry-oriented reagent selection, library design, and
      profiling platform.
AB  - REALISIS is a software system for reagent selection, library design, and
      profiling, developed to fit the workflow of bench chemists and medicinal
      chemists. Designed to be portable, the software offers a comprehensive graphical
      user interface and rapid, integrated functionalities required for reagent
      retrieval and filtering, product enumeration, and library profiling. REALISIS is
      component-based, consisting of four main modules: reagent searching; reagent
      filtering; library enumeration; and library profiling. Each module allows the
      chemist to access specific functionalities and diverse filtering and profiling
      mechanisms. By implementing the entire process of reagent selection, library
      design, and profiling and by integrating all the necessary functionalities for
      this process, REALISIS cuts the time required to design combinatorial and
      noncombinatorial libraries from several days to a few hours.

PMID- 15554691
TI  - Generalization of a targeted library design protocol: application to 5-HT7
      receptor ligands.
AB  - Herein a general concept for the design of targeted libraries for proteins with
      binding sites that are divided into subsites is laid out, including several
      practical aspects and their solutions. The design is based on a chemogenomic
      classification of the subsites followed by collection of bioactive molecular
      fragments and virtual library generation. The general process is outlined and
      applied to the assembly of a library of 500 molecules targeting the serotonin
      type 7 (5-HT7) receptor, a class A G-Protein Coupled Receptor (GPCR). Utilizing
      commercially available building blocks of similar size and composition, a
      reference library was created. Control sets of known ligands for the 5-HT7
      receptor, other GPCRs, and nuclear receptors were collected from literature
      sources. Principal component analysis of molecular descriptors for the two
      libraries and the literature sets, displayed a focusing of the targeted library
      to the region in the chemical space defined by the literature actives, suggesting
      a denser coverage of the bioactive region than for the more diverse reference
      library. Additional computational validations, including PCA class predictions,
      3D pharmacophore modeling, and docking calculations all indicated an enrichment
      factor of 5-HT7 ligand-like molecules in the range of 2-4 for the targeted
      library compared to the reference library.

PMID- 15554692
TI  - Application of machine learning to improve the results of high-throughput docking
      against the HIV-1 protease.
AB  - We have previously reported that the application of a Laplacian-modified naive
      Bayesian (NB) classifier may be used to improve the ranking of known inhibitors
      from a random database of compounds after High-Throughput Docking (HTD). The
      method relies upon the frequency of substructural features among the active and
      inactive compounds from 2D fingerprint information of the compounds. Here we
      present an investigation of the role of extended connectivity fingerprints in
      training the NB classifier against HTD studies on the HIV-1 protease using three
      docking programs: Glide, FlexX, and GOLD. The results show that the performance
      of the NB classifier is due to the presence of a large number of features common
      to the set of known active compounds rather than a single structural or
      substructural scaffold. We demonstrate that the Laplacian-modified naive Bayesian
      classifier trained with data from high-throughput docking is superior at
      identifying active compounds from a target database in comparison to conventional
      two-dimensional substructure search methods alone.

PMID- 15554694
TI  - Crystal structure of the PH-BEACH domains of human LRBA/BGL.
AB  - The beige and Chediak-Higashi syndrome (BEACH) domain defines a large family of
      eukaryotic proteins that have diverse cellular functions in vesicle trafficking,
      membrane dynamics, and receptor signaling. The domain is the only module that is
      highly conserved among all of these proteins, but the exact functions of this
      domain and the molecular basis for its actions are currently unknown. Our
      previous studies showed that the BEACH domain is preceded by a novel, weakly
      conserved pleckstrin homology (PH) domain. We report here the crystal structure
      at 2.4 A resolution of the PH-BEACH domain of human LRBA/BGL. The PH domain has
      the same backbone fold as canonical PH domains, despite sharing no sequence
      homology with them. However, our binding assays demonstrate that the PH domain in
      the BEACH proteins cannot bind phospholipids. The BEACH domain contains a core of
      several partially extended peptide segments that is flanked by helices on both
      sides. The structure suggests intimate association between the PH and the BEACH
      domains, and surface plasmon resonance studies confirm that the two domains of
      the protein FAN have high affinity for each other, with a K(d) of 120 nM.

PMID- 15554695
TI  - Light-induced structural changes of LOV domain-containing polypeptides from
      Arabidopsis phototropin 1 and 2 studied by small-angle X-ray scattering.
AB  - Phototropin is a blue-light receptor of plants and comprises two light-receptive
      domains, LOV1 and LOV2, Ser/Thr kinase domain and one linker region connecting
      the LOV2 and the kinase domains. The LOV2 domain is thought to regulate
      predominantly the light-dependent autophosphorylation of the kinase domain,
      leading to cellular signaling cascades. In this study, we constructed recombinant
      LOV1, LOV2, and LOV2-linker polypeptides from phototropin 1 and phototropin 2 of
      Arabidopsis thaliana and studied their quaternary structures and light-dependent
      conformational changes by small-angle X-ray scattering. The molecular weights of
      the polypeptides determined from scattering intensities demonstrated the dimeric
      associations of LOV1 polypeptides of both isoforms. In contrast, while LOV2 and
      LOV2-linker polypeptides of phototropin 1 were homodimers, corresponding
      polypeptides of phototropin 2 existed as monomeric forms. Under blue-light
      irradiation, the LOV2-linker polypeptide of phototropin 1 displayed small but
      definite changes of the scattering profile. Through simulation of low-resolution
      molecular structures, the changes were likely explained as structural changes of
      the linker region and/or a movement of the region relative to the LOV2 domain.
      Light-induced profile changes were not observed in the Cys(512)Ala mutated LOV2
      linker polypeptide of phototropin 1 losing the phototransformation capability.
      Thus, it was indicated that the photoreaction in the LOV2 domain probably caused
      the structural changes in the LOV2-linker polypeptide of phototropin 1. On the
      basis of the results, the interdomain interactions in phototropin are discussed.

PMID- 15554696
TI  - Kinetics and thermodynamics of the unfolding and refolding of the three-stranded
      alpha-helical coiled coil, Lpp-56.
AB  - Temperature-induced reversible unfolding and refolding of the three-stranded
      alpha-helical coiled coil, Lpp-56, were studied by kinetic and thermodynamic
      methods, using CD spectroscopy, dynamic light scattering, and scanning
      calorimetry. It was found that both unfolding and refolding reactions of this
      protein in neutral solution in the presence of 100 mM NaCl are characterized by
      unusually slow kinetics, which permits detailed investigation of the mechanism of
      these reactions. Kinetic analyses show that the unfolding of this coiled coil
      represents a single-stage first-order reaction, while the refolding represents a
      single-stage third-order reaction. The activation enthalpy and entropy for
      unfolding do not depend noticeably on temperature and are both significantly
      greater than those for the folding reaction, which show a significant dependence
      on temperature. The activation heat capacity change for the unfolding reaction is
      close to zero, while it is quite significant for the folding reaction. The
      correlation between the activation and structural parameters obtained for the Lpp
      56 coiled coil suggests that interhelical van der Waals interactions are
      disrupted in the transition state, which is nevertheless still compact, and water
      has not yet penetrated into the interface; the transition from the transient
      state to the unfolded state results in hydration of exposed apolar groups of the
      interface and the disruption of helices. The low propensity for the Lpp-56
      strands to fold and associate is caused by the high number of charged groups at
      neutral pH. On one hand, these charges give rise to considerable repulsive forces
      destabilizing the helical conformation of the strands. On the other hand, they
      align the folded helices in parallel and in register so that the apolar sides
      face each other, and the oppositely charged groups may form salt links, which are
      important for the formation of the trimeric coiled coil. A decrease in pH, which
      eliminates the salt links, dramatically decreases the stability of Lpp-56; its
      structure becomes less rigid and unfolds much faster.

PMID- 15554697
TI  - Interactions of inorganic phosphate and sulfate anions with collagen.
AB  - We use direct infrared measurements to determine the number of binding sites,
      their dissociation constants, and preferential interaction parameters for
      inorganic phosphate and sulfate anions in collagen fibrils from rat tail tendons.
      In contrast to previous reports of up to 150 bound phosphates per collagen
      molecule, we find only 1-2 binding sites for sulfate and divalent phosphate under
      physiological conditions and approximately 10 binding sites at low ionic
      strength. The corresponding dissociation constants depend on NaCl concentration
      and pH and vary from approximately 50 microM to approximately 1-5 mM in the
      physiological range of pH. In fibrils, bound anions appear to form salt bridges
      between positively charged amino acid residues within regions of high excess
      positive charge. In solution, we found no evidence of appreciable sulfate or
      phosphate binding to isolated collagen molecules. Although sulfate and divalent
      phosphate bind to fibrillar collagen at physiological concentrations, our X-ray
      diffraction and in vitro fibrillogenesis experiments suggest that this binding
      plays little role in the formation, stability and structure of fibrils. In
      particular, we demonstrate that the previously reported increase in the critical
      fibrillogenesis concentration of collagen is caused by preferential exclusion of
      "free" (not bound to specific sites) sulfate and divalent phosphate from
      interstitial water in fibrils rather than by anion binding. Contrary to divalent
      phosphate, monovalent phosphate does not bind to collagen. It is preferentially
      excluded from interstitial water in fibrils, but it has no apparent effect on
      critical fibrillogenesis concentration at physiological NaCl and pH.

PMID- 15554698
TI  - Comparative studies on the structure and stability of fluorescent proteins EGFP,
      zFP506, mRFP1, "dimer2", and DsRed1.
AB  - To obtain more information about the structural properties and conformational
      stabilities of GFP-like fluorescent proteins, we have undertaken a systematic
      analysis of series of green and red fluorescent proteins with different
      association states. The list of studied proteins includes EGFP (green monomer),
      zFP506 (green tetramer), mRFP1 (red monomer), "dimer2" (red dimer), and DsRed1
      (red tetramer). Fluorescent and absorbance parameters, near-UV and visible CD
      spectra, the accessibility of the chromophores and tryptophans to acrylamide
      quenching, and the resistance of these proteins to the guanidine hydrochloride
      unfolding and kinetics of the approaching of the unfolding equilibrium have been
      compared. Tetrameric zFP506 was shown to be dramatically more stable than the
      EGFP monomer, assuming that association might contribute to the protein
      conformational stability. This assumption is most likely valid even though the
      sequences OF GFP and zPF506 are only approximately 25% identical. Interestingly,
      red FPs possessed comparable conformational stabilities, where monomeric mRFP1
      was the most stable species under the equilibrium conditions, whereas the
      tetrameric DsRed1 possessed the slowest unfolding kinetics. Furthermore, EGFP is
      shown to be considerably less stable than mRFP1, whereas tetrameric zFP506 is the
      most stable species analyzed in this study. This means that the quaternary
      structure, being an important stabilizing factor, does not represent the only
      circumstance dictating the dramatic variations between fluorescent proteins in
      their conformational stabilities.

PMID- 15554699
TI  - Influence of C-terminal protein domains and protein-lipid interactions on
      tetramerization and stability of the potassium channel KcsA.
AB  - KcsA is a prokaryotic potassium channel formed by the assembly of four identical
      subunits around a central aqueous pore. Although the high-resolution X-ray
      structure of the transmembrane portion of KcsA is known [Doyle, D. A., Morais, C.
      J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., and
      MacKinnon, R. (1998) Science 280, 69-77], the identification of the molecular
      determinant(s) involved in promoting subunit tetramerization remains to be
      determined. Here, C-terminal deletion channel mutants, KcsA Delta125-160 and
      Delta120-160, as well as 1-125 KcsA obtained from chymotrypsin cleavage of full
      length 1-160 KcsA, have been used to evaluate the role of the C-terminal segment
      on the stability and tetrameric assembly of the channel protein. We found that
      the lack of the cytoplasmic C-terminal domain of KcsA, and most critically the
      120-124 sequence stretch, impairs tetrameric assembly of channel subunits in a
      heterologous E. coli expression system. Molecular modeling of KcsA predicts that,
      indeed, such sequence stretch provides intersubunit interaction sites by hydrogen
      bonding to amino acid residues in N- and C-terminal segments of adjacent
      subunits. However, once the KcsA tetramer is assembled, its remarkable in vitro
      stability to detergent or to heat-induced dissociation into subunits is not
      greatly influenced by whether the entire C-terminal domain continues being part
      of the protein. Finally and most interestingly, it is observed that, even in the
      absence of the C-terminal domain involved in tetramerization, reconstitution into
      membrane lipids promotes in vitro KcsA tetramerization very efficiently, an event
      which is likely mediated by allowing proper hydrophobic interactions involving
      intramembrane protein domains.

PMID- 15554700
TI  - Characterization of Lck-binding elements in the herpesviral regulatory Tip
      protein.
AB  - Herpesvirus saimiri encodes a tyrosine kinase interacting protein (Tip) that
      binds to T-cell-specific tyrosine kinase Lck via multiple sequence motifs and
      controls its activity. The regulation of Lck by Tip represents a key mechanism in
      the transformation of human T-lymphocytes during herpesviral infection. In this
      study, the interaction of Tip with the regulatory SH3 and SH2 domains of Lck was
      investigated by biophysical and computational techniques. NMR spectroscopy of
      isotopically labeled Tip(140-191) revealed that the interaction with the LckSH3
      domain is not restricted to the classical proline-rich motif, but also involves
      the C-terminally adjacent residues which pack into a hydrophobic pocket on the
      surface of the SH3 domain, thus playing a likely role in mediating binding
      specificity. Fluorescence binding studies of Tip further demonstrate that Tyr127
      in its phosphorylated form represents a strong ligand of the LckSH2 domain,
      indicating the presence of an additional Lck interaction motif. In contrast,
      Tyr114, known to be essential for STAT-3 binding, does not interact with the
      LckSH2 domain, showing that the tyrosines in Tip exhibit distinct binding
      specificity. The existence of numerous interaction sites between Tip and the
      regulatory domains of Lck implies a complex regulatory mechanism and may have
      evolved to allow a gradual regulation of Lck activity in different pathogenic
      states.

PMID- 15554701
TI  - NMR solution structure and membrane interaction of the N-terminal sequence (1-30)
      of the bovine prion protein.
AB  - The structure and membrane interaction of the N-terminal sequence (1-30) of the
      bovine prion protein (bPrPp) has been investigated by NMR spectroscopy in
      phospholipid membrane mimetic systems. CD spectroscopy revealed that the peptide
      adopts a largely alpha-helical structure in zwitterionic bicelles as well as in
      DHPC micelles but has a less degree of alpha-helix structure in partly charged
      bicelles. The solution structure of bPrPp was determined in DHPC micelles, and an
      alpha-helix was found between residues Ser8 and Ile21. The residues within the
      helical region show slow amide hydrogen exchange. Translational diffusion
      measurements in zwitterionic q = 0.5 bicelles show that the peptide does not
      induce aggregation of the bicelles. Increased quadrupolar splittings were
      observed in the outer part of the (2)H spectrum of DMPC in q = 3.5 bicelles,
      indicating that the peptide induces a certain degree of order in the bilayer. The
      amide hydrogen exchange and the (2)H NMR results are consistent with a slight
      positive hydrophobic mismatch and that bPrPp forms a stable helix that inserts in
      a transmembrane location in the bilayer. The structure of bPrPp and its position
      in the membrane may be relevant for the understanding of how the N-terminal (1
      30) part of the bovine PrP functions as a cell-penetrating peptide. These
      findings may lead to a better understanding of how the prion protein accumulates
      at the membrane surface and also how the conversion into the scrapie form is
      carried out.

PMID- 15554702
TI  - Interaction between muscle aldolase and muscle fructose 1,6-bisphosphatase
      results in the substrate channeling.
AB  - Fructose 1,6-bisphosphatase (FBPase) is known to form a supramolecular complex
      with alpha-actinin and aldolase on both sides of the Z-line in skeletal muscle
      cells. It has been proposed that association of aldolase with FBPase not only
      desensitizes muscle FBPase toward AMP inhibition but it also might enable the
      channeling of intermediates between the enzymes [Rakus et al. (2003) FEBS Lett.
      547, 11-14]. In the present paper, we tested the possibility of fructose 1,6
      bisphosphate (F1,6-P(2)) channeling between aldolase and FBPase using the
      approach in which an inactive form of FBPase competed with active FBPase for
      binding to aldolase and thus decreased the rate of aldolase-FBPase reaction. The
      results showed that F1,6-P(2) is transferred directly from aldolase to FBPase
      without mixing with the bulk phase. Further evidence that F1,6-P(2) is channeled
      from aldolase to FBPase comes from the experiments investigating the inhibitory
      effect of a high concentration of magnesium ions on aldolase-FBPase activity.
      FBPase in a complex with aldolase, contrary to free muscle FBPase, was not
      inhibited by high Mg(2+) concentrations, which suggests that free F1,6-P(2) was
      not present in the assay mixture during the reaction. A real-time interaction
      analysis between aldolase and FBPase revealed a dual role of Mg(2+) in the
      regulation of the aldolase-FBPase complex stability. A physiological
      concentration of Mg(2+) increased the affinity of muscle FBPase to muscle
      aldolase, whereas higher concentrations of the cation decreased the concentration
      of the complex. We hypothesized that the presence of Mg(2+) stabilizes a
      positively charged cavity within FBPase and that it might enable an interaction
      with aldolase. Because magnesium decreased the binding constant (K(a)) between
      aldolase and FBPase in a manner similar to the decrease of K(a) caused by
      monovalent cations, it is postulated that electrostatic attraction might be a
      driving force for the complex formation. It is presumed that the biological
      relevance of F1,6-P(2) channeling between aldolase and FBPase is protection of
      this glyconeogenic, as well as glycolytic, intermediate against degradation by
      cytosolic aldolase, which is one of the most abundant enzyme of glycolysis.

PMID- 15554703
TI  - Quaternary structure of the severe acute respiratory syndrome (SARS) coronavirus
      main protease.
AB  - SARS (severe acute respiratory syndrome) has been one of the most severe viral
      infectious diseases last year and still remains as a highly risky public health
      problem around the world. Exploring the types of interactions responsible for
      structural stabilities of its component protein molecules constitutes one of the
      approaches to find a destabilization method for the virion particle. In this
      study, we performed a series of experiments to characterize the quaternary
      structure of the dimeric coronavirus main protease (M(pro), 3CL(pro)). By using
      the analytical ultracentrifuge, we demonstrated that the dimeric SARS coronavirus
      main protease exists as the major form in solution at protein concentration as
      low as 0.10 mg/mL at neutral pH. The enzyme started to dissociate at acidic and
      alkali pH values. Ionic strength has profound effect on the dimer stability
      indicating that the major force involved in the subunit association is ionic
      interactions. The effect of ionic strength on the protease molecule was reflected
      by the drastic change of electrostatic potential contour of the enzyme in the
      presence of NaCl. Analysis of the crystal structures indicated that the
      interfacial ionic interaction was attributed to the Arg-4...Glu-290 ion pair
      between the subunits. Detailed examination of the dimer-monomer equilibrium at
      different pH values reveals apparent pK(a) values of 8.0 +/- 0.2 and 5.0 +/- 0.1
      for the Arg-4 and Glu-290, respectively. Mutation at these two positions reduces
      the association affinity between subunits, and the Glu-290 mutants had diminished
      enzyme activity. This information is useful in searching for substances that can
      intervene in the subunit association, which is attractive as a target to
      neutralize the virulence of SARS coronavirus.

PMID- 15554704
TI  - NMR solution structure of the archaebacterial chromosomal protein MC1 reveals a
      new protein fold.
AB  - The three-dimensional structure of methanogen chromosomal protein 1 (MC1), a
      chromosomal protein extracted from the archaebacterium Methanosarcina sp. CHTI55,
      has been solved using (1)H NMR spectroscopy. The small basic protein MC1 contains
      93 amino acids (24 basic residues against 12 acidic residues). The main elements
      of secondary structures are an alpha helix and five beta strands, arranged as two
      antiparallel beta sheets (a double one and a triple one) packed in an orthogonal
      manner forming a barrel. The protein displays a largely hydrophilic surface and a
      very compact hydrophobic core made up by side chains at the interface of the two
      beta sheets and the helix side facing the interior of the protein. The MC1
      solution structure shows a globular protein with overall dimensions in the range
      of 34-40 A, which potentially corresponds to a DNA-binding site of 10-12 base
      pairs. The presumed DNA-binding site is located on the sequence comprising
      residues K62-P82, which is formed by a part of strands II2 and II3 belonging to
      the triple-stranded antiparallel beta sheet and a loop flanked by prolines P68
      and P76. The tryptophan W74 that is expected to play a key role in the DNA
      binding according to photocross-linking experiments was found completely exposed
      to the solvent, in a good position to interact with DNA. The overall fold of MC1,
      characterized by its linking beta-beta-alpha-beta-beta-loop-beta, is different
      from other known DNA-binding proteins. Its structure suggests a different DNA
      binding mode than those of the histone-like proteins HU or HMGB. Thus, MC1 may be
      classified as a member of a new family.

PMID- 15554705
TI  - Structural intermediate in the photocycle of a BLUF (sensor of blue light using
      FAD) protein Slr1694 in a Cyanobacterium Synechocystis sp. PCC6803.
AB  - Slr1694 in Synechocystis sp. PCC6803 is a family of blue-light photoreceptors
      based on flavin adenine dinucleotide (FAD) called BLUF (sensor of blue light
      using FAD) proteins, which include AppA from Rhodobacter sphaeroides and PAC from
      Euglena gracilis. Illumination of dark-state Slr1694 at 15 degrees C reversibly
      induced a signaling light state characterized by the red shift in the UV-visible
      spectrum and by the light-induced Fourier transform infrared (FTIR) difference
      spectrum for structural changes of a bound flavin and apo protein. Illumination
      at the medium-low temperature (-35 degrees C) led to the red shift in the UV
      visible spectrum despite some small difference in the light-induced changes. In
      contrast, the -35 degrees C illumination resulted in a completely different light
      induced FTIR spectrum, in which almost all of the bands were suppressed with the
      exception of the bands for the change of C4=O bonding of the FAD isoalloxazine
      ring. The C4=O bands were induced at -35 degrees C with almost the same
      intensity, but the band frequency for the light state was upshifted by 6 cm(
      )(1). The changes in frequency of the light-state C4=O band and in amplitude of
      other bands showed the same temperature dependence with a half-change temperature
      at approximately -20 degrees C. It was indicated that the light-induced
      structural changes of apo protein and FAD were inhibited at low temperature with
      the exception of the change in hydrogen bonding to the C4=O group. The light
      induced formation of the FTIR bands was similarly inhibited by sample
      dehydration. We discussed the possibility that this constrained light state is a
      trapped intermediate state in the photocycle of Slr1694.

PMID- 15554706
TI  - Strength of integration of transmembrane alpha-helical peptides in lipid bilayers
      as determined by atomic force spectroscopy.
AB  - In this study we address the stability of integration of proteins in membranes.
      Using dynamic atomic force spectroscopy, we measured the strength of
      incorporation of peptides in lipid bilayers. The peptides model the transmembrane
      parts of alpha-helical proteins and were studied in both ordered peptide-rich and
      unordered peptide-poor bilayers. Using gold-coated AFM tips and thiolated
      peptides, we were able to observe force events which are related to the removal
      of single peptide molecules out of the bilayer. The data demonstrate that the
      peptides are very stably integrated into the bilayer and that single barriers
      within the investigated region of loading rates resist their removal. The
      distance between the ground state and the barrier for peptide removal was found
      to be 0.75 +/- 0.15 nm in different systems. This distance falls within the
      thickness of the interfacial layer of the bilayer. We conclude that the bilayer
      interface region plays an important role in stably anchoring transmembrane
      proteins into membranes.

PMID- 15554707
TI  - Ribonuclease activity of vaccinia DNA topoisomerase IB: kinetic and high
      throughput inhibition studies using a robust continuous fluorescence assay.
AB  - Vaccinia type I DNA topoisomerase exhibits a strong site-specific ribonuclease
      activity when provided a DNA substrate that contains a single uridine
      ribonucleotide within a duplex DNA containing the sequence 5' CCCTU 3'. The
      reaction involves two steps: attack of the active site tyrosine nucleophile of
      topo I at the 3' phosphodiester of the uridine nucleotide to generate a covalent
      enzyme-DNA adduct, followed by nucleophilic attack of the uridine 2'-hydroxyl to
      release the covalently tethered enzyme. Here we report the first continuous
      spectroscopic assay for topoisomerase that allows monitoring of the ribonuclease
      reaction under multiple-turnover conditions. The assay is especially robust for
      high-throughput screening applications because sensitive molecular beacon
      technology is utilized, and the topoisomerase is released during the reaction to
      allow turnover of multiple substrate molecules by a single molecule of enzyme.
      Direct computer simulation of the fluorescence time courses was used to obtain
      the rate constants for substrate binding and release, covalent complex formation,
      and formation of the 2',3'-cyclic phosphodiester product of the ribonuclease
      reaction. The assay allowed rapid screening of a 500 member chemical library from
      which several new inhibitors of topo I were identified with IC(50) values in the
      range of 2-100 microM. Three of the most potent hits from the high-throughput
      screening were also found to inhibit plasmid supercoil relaxation by the enzyme,
      establishing the utility of the assay in identifying inhibitors of the
      biologically relevant DNA relaxation reaction. One of the most potent inhibitors
      of the vaccinia enzyme, 3-benzo[1,3]dioxol-5-yl-2-oxoproprionic acid, did not
      inhibit the closely related human enzyme. The inhibitory mechanism of this
      compound is unique and involves a step required for recycling the enzyme for
      steady-state turnover.

PMID- 15554708
TI  - Mutagenic properties of 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, a
      persistent acetylaminofluorene-derived DNA adduct in mammalian cells.
AB  - The carcinogen 2-acetylaminofluorene is metabolically activated in cells and
      reacts with DNA to form N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-C8-AAF),
      N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), and 3-(deoxyguanosin-N(2)()
      yl)-2-acetylaminofluorene (dG-N(2)-AAF) DNA adducts. The dG-N(2)-AAF adduct is
      the least abundant of the three isomers, but it persists in the tissues of
      animals treated with this carcinogen. The miscoding and mutagenic properties of
      dG-C8-AAF and dG-C8-AF have been established; these adducts are readily excised
      by DNA repair enzymes engaged in nucleotide excision repair. In the present
      study, oligodeoxynucleotides modified site-specifically with dG-N(2)-AAF were
      used as DNA templates in primer extension reactions catalyzed by mammalian DNA
      polymerases. Reactions catalyzed by pol alpha were strongly blocked at a position
      one base before dG-N(2)-AAF and also opposite this lesion. In contrast, during
      translesion synthesis catalyzed by pol eta or pol kappa nucleotides were
      incorporated opposite the lesion. Both pol eta and pol kappa incorporated dCMP,
      the correct base, opposite dG-N(2)-AAF. In reactions catalyzed by pol eta, small
      amounts of dAMP misincorporation and one-base deletions were detected at the
      lesion site. With pol kappa, significant dTMP misincorporation was observed
      opposite the lesion. Steady-state kinetic analysis confirmed the results obtained
      from primer extension studies. Single-stranded shuttle vectors containing
      (5)(')TCCTCCTCXCCTCTC (X = dG-N(2)-AAF, dG-C8-AAF, or dG) were used to establish
      the frequency and specificity of dG-N(2)-AAF-induced mutations in simian kidney
      (COS-7) cells. Both lesions promote G --> T transversions overall, with dG-N(2)
      AAF being less mutagenic than dG-C8-AAF (3.4% vs 12.5%). We conclude from this
      study that dG-N(2)-AAF, by virtue of its persistence in tissues, contributes
      significantly to the mutational spectra observed in AAF-induced mutagenesis and
      that pol eta, but not pol kappa, may play a role in this process.

PMID- 15554709
TI  - trans-Beta-nitrostyrene derivatives as slow-binding inhibitors of protein
      tyrosine phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphotyrosyl
      (pY) proteins to produce tyrosyl proteins and inorganic phosphate. Specific PTPs
      inhibitors provide useful tools for studying PTP function in signal transduction
      processes and potential treatment for human diseases such as diabetes,
      inflammation, and cancer. In this work, trans-beta-nitrostyrene (TBNS) and its
      derivatives are found to be slow-binding inhibitors against protein tyrosine
      phosphatases PTP1B, SHP-1, and Yop with moderate potencies (K(I*) = 1-10 microM).
      Competition experiments with a substrate (pNPP) and iodoacetate indicate that
      TBNS is active site-directed. The mechanism of inhibition was investigated by UV
      vis absorption spectroscopy, (1)H-(13)C heteronuclear single-quantum correlation
      NMR spectroscopy, and site-directed mutagenesis. These studies suggested a
      mechanism in which TBNS acts a pY mimetic and binds to the PTP active site to
      form an initial noncovalent E.I complex, followed by nucleophilic attack on the
      TBNS nitro group by Cys-215 of PTP1B to form a reversible, covalent adduct as the
      tighter E.I* complex. TBNS derivatives represent a new class of neutral pY
      mimetic inhibitors of PTPs.

PMID- 15554710
TI  - Assembly of dimeric variants of coumermycins by tandem action of the four
      biosynthetic enzymes CouL, CouM, CouP, and NovN.
AB  - Coumermycin A(1) is a member of the aminocoumarin family of antibiotics. Unlike
      its structural relatives, novobiocin and clorobiocin, coumermycin A(1) is a dimer
      built on a 3-methyl-2,4-dicarboxypyrrole scaffold and bears two decorated noviose
      sugar components which are the putative target binding motifs for DNA gyrase.
      Starting with this scaffold, we have utilized the ligase CouL for mono- and
      bisamide formation with aminocoumarins to provide substrates for the
      glycosyltransferase CouM. CouM was subsequently shown to catalyze mono- and
      bisnoviosylation of the resulting CouL products. CouP was shown to possess 4'-O
      methyltransferase activity on products from tandem CouL, CouM assays. A fourth
      enzyme, NovN, the 3'-O-carbamoyltransferase from the novobiocin operon, was then
      able to carbamoylate either or both arms of the CouP product. The tandem action
      of CouL, CouM, CouP, and NovN thus generates a biscarbamoyl analogue of the
      pseudodimer coumermycin A(1). Starting from alternative dicarboxy scaffolds,
      these four enzymes can be utilized in tandem to create additional variants of
      dimeric aminocoumarin antibiotics.

PMID- 15554711
TI  - Stimulus-dependent dynamic homo- and heteromultimerization of synaptobrevin/VAMP
      and synaptophysin.
AB  - Synaptophysin and synaptobrevin/VAMP are abundant synaptic vesicle proteins that
      form homo- and heterooligomers. We now use chemical cross-linking in
      synaptosomes, pinched-off nerve terminals that are capable of stimulus-dependent
      neurotransmitter release, to investigate whether these complexes are regulated.
      We show that in synaptosomes treated with three stimuli that induce exocytosis (a
      depolarizing K(+) solution, the excitatory neurotoxin alpha-latrotoxin, or the
      Ca(2+)-ionophore ionomycin), the homo- and heteromultimerization of synaptophysin
      and synaptobrevin is increased up to 6-fold. Whereas at rest less than 10% of the
      total synaptobrevin and synaptophysin could be chemically cross-linked into homo-
      and heteromeric complexes, after stimulation up to 25% of synaptobrevin and
      synaptophysin are present in homo- and heteromultimers, suggesting that a large
      fraction of these synaptic vesicle proteins physiologically participate in such
      complexes. The increase in multimerization of synaptophysin and synaptobrevin was
      only observed in intact but not in lysed synaptosomes and could not be inhibited
      by general kinase or phosphatase inhibitors. The stimulus dependence of
      synaptophysin and synaptobrevin multimers indicates that the complexes are not
      composed of a fixed multisubunit structure, for example, as an ion channel, but
      represent distinct functional states of synaptobrevin and synaptophysin that are
      modulated in parallel with synaptic vesicle exo- and endocytosis.

PMID- 15554712
TI  - Dynamics of urokinase receptor interaction with Peptide antagonists studied by
      amide hydrogen exchange and mass spectrometry.
AB  - Using amide hydrogen exchange combined with electrospray ionization mass
      spectrometry, we have in this study determined the number of amide hydrogens on
      several peptides that become solvent-inaccessible as a result of their high
      affinity interaction with the urokinase-type plasminogen activator receptor
      (uPAR). These experiments reveal that at least six out of eight amide hydrogens
      in a synthetic nine-mer peptide antagonist (AE105) become sequestered upon
      engagement in uPAR binding. Various uPAR mutants with decreased affinity for this
      peptide antagonist gave similar results, thereby indicating that deletion of the
      favorable interactions involving the side chains of these residues in uPAR does
      not affect the number of hydrogen bonds established by the main chain of the
      peptide ligand. The isolated growth factor-like domain (GFD) of the cognate
      serine protease ligand for uPAR showed 11 protected amide hydrogens in the
      receptor complex. Interestingly, a naturally occurring O-linked fucose on Thr(18)
      confers protection of two additional amide hydrogens in GFD when it forms a
      complex with uPAR. Dissociation of the uPAR-peptide complexes is accompanied by a
      correlated exchange of nearly all amide hydrogens on the peptide ligand. This
      yields bimodal isotope patterns from which dissociation rate constants can be
      determined. In addition, the distinct bimodal isotope distributions also allow
      investigation of the exchange kinetics of receptor-bound peptides providing
      information about the local structural motions at the interface. These exchange
      experiments therefore provide both structural and kinetic information on the
      interaction between uPAR and these small peptide antagonists, which in model
      systems show promise as inhibitors of intravasation of human cancer cells.

PMID- 15554713
TI  - Cardiac myosin isoforms from different species have unique enzymatic and
      mechanical properties.
AB  - The mammalian heart contains two cardiac myosin isoforms: beta-myosin heavy chain
      (MHC) is found predominantly in the ventricles of large mammals, and alpha-MHC is
      expressed in the atria. The sequence identity between these isoforms is
      approximately 93%, with nonidentical residues clustered in discrete, functionally
      important domains associated with actin binding and ATPase activity. It is well
      established that rabbit alpha-cardiac myosin has a 2-fold greater unloaded
      shortening velocity than beta-cardiac myosin but a 2-fold lower average isometric
      force. Here, we test the generality of these relationships for another large
      mammal, the pig, as well as for a small rodent, the mouse, which expresses alpha
      MHC in its ventricles throughout adulthood. Hydrophobic interaction
      chromatography (HIC) was used to purify myosin from mouse, rabbit, and pig
      hearts. The superior resolving power of HIC made it possible to prepare highly
      homogeneous, enzymatically active myosin from small amounts of tissue. The
      movement of actin filaments by myosin was measured in an in vitro motility assay.
      The same assay could be used to determine average isometric force by loading the
      actin filaments with increasing concentrations of alpha-actinin to stop filament
      motion. We conclude that myosin from the mouse has significantly higher
      velocities for both alpha and beta isoforms than myosin from rabbits and pigs,
      even though the 2-fold difference in velocity between isoforms is maintained.
      Unlike the larger mammals, however, the small rodent generates the same high
      isometric force for both alpha and beta isoforms. Thus, nature has adapted the
      function of cardiac myosin isoforms to optimize power output for hearts of a
      given species.

PMID- 15554714
TI  - Neosynthesis of cardiolipin in Rhodobacter sphaeroides under osmotic stress.
AB  - The phospholipid composition of Rhodobacter sphaeroides cells resuspended in
      various hypertonic solutions has been examined by thin-layer chromatography and
      ESI mass spectrometry. R. sphaeroides responds to hyperosmotic stress by
      increasing the amount of cardiolipin in the membranes; this phenomenon occurs in
      spheroplasts also. Cardiolipin increases quickly and continuously during the time
      when the cells are resuspended in hypertonic medium. The optimum of stimulation
      of the neosynthesis of cardiolipin during osmotic stress was found to be at
      external 1 osm. ESI-MS analyses allowed the identification of two different
      cardiolipins in R. sphaeroides: the tetravaccenylcardiolipin ([M - H](-), m/z
      1456.9) and the trivaccenylmonopalmitoylcardiolipin ([M - H](-), m/z 1430.0).

PMID- 15554715
TI  - Formation of a complex of the catalytic subunit of pyruvate dehydrogenase
      phosphatase isoform 1 (PDP1c) and the L2 domain forms a Ca2+ binding site and
      captures PDP1c as a monomer.
AB  - Pyruvate dehydrogenase phosphatase isoform 1 (PDP1) is a heterodimer with a
      catalytic subunit (PDP1c) and a regulatory subunit (PDP1r). The activities of
      PDP1 or just PDP1c are greatly increased by Ca(2+)-dependent binding to the L2
      (inner lipoyl) domain of the dihydrolipoyl acetyltransferase (E2) core. Using
      EGTA-Ca buffers, the dependence of PDP1 or PDP1c on the level of free Ca(2+) was
      evaluated in activity and L2 binding studies. An increase in the Mg(2+)
      concentration decreased the Ca(2+) concentration required for half-maximal
      activation of PDP1 from 3 to 1 microM, but this parameter was unchanged at 3
      microM with PDP1c. Near 1 microM Ca(2+), tight binding of PDP1 but not PDP1c to
      gel-anchored L2 required Mg(2+). With just Ca(2+) included, some PDP1c separated
      from PDP1r and remained more tightly bound to L2 than intact PDP1. Thus,
      formation of the PDP1c.Ca(2+).L2 complex is supported by micromolar Ca(2+)
      concentrations and becomes sensitive to the Mg(2+) level when PDP1c is bound to
      PDP1r. Sedimentation velocity and equilibrium studies revealed that PDP1c exists
      as a reversible monomer/dimer mixture with an equilibrium dissociation constant
      of 8.0 +/- 2.5 microM. L2 binds tightly and preferentially to the PDP1c monomer.
      Approximately 45 PDP1c monomers bind to the E2 60mer with a K(d) of approximately
      0.3 microM. Isothermal titration calorimetry and (45)Ca(2+) binding studies
      failed to detect binding of Ca(2+) (<100 microM) to L2 or PDP1c, alone, but
      readily detected binding to L2 and PDP1c. Therefore, both proteins are required
      for formation of a complex with tightly held Ca(2+), and complex formation
      hinders the tendency of PDP1c to form a dimer.

PMID- 15554716
TI  - Resolving complexity in the interactions of redox enzymes and their inhibitors:
      contrasting mechanisms for the inhibition of a cytochrome c nitrite reductase
      revealed by protein film voltammetry.
AB  - Cytochrome c nitrite reductase is a dimeric decaheme-containing enzyme that
      catalyzes the reduction of nitrite to ammonium. The contrasting effects of two
      inhibitors on the activity of this enzyme have been revealed, and defined, by
      protein film voltammetry (PFV). Azide inhibition is rapid and reversible.
      Variation of the catalytic current magnitude describes mixed inhibition in which
      azide binds to the Michaelis complex (approximately 40 mM) with a lower affinity
      than to the enzyme alone (approximately 15 mM) and leads to complete inhibition
      of enzyme activity. The position of the catalytic wave reports tighter binding of
      azide when the active site is oxidized (approximately 39 microM) than when it is
      reduced. By contrast, binding and release of cyanide are sluggish. The higher
      affinity of cyanide for reduced versus oxidized forms of nitrite reductase is
      immediately revealed, as is the presence of two sites for cyanide binding and
      inhibition of the enzyme. Formation of the monocyano complex by reduction of the
      enzyme followed by a "rapid" scan to high potentials captures the activity
      potential profile of this enzyme form and shows it to be distinct from that of
      the uninhibited enzyme. The biscyano complex is inactive. These studies
      demonstrate the complexity that can be associated with inhibitor binding to redox
      enzymes and illustrate how PFV readily captures and deconvolves this complexity
      through its impact on the catalytic properties of the enzyme.

PMID- 15554717
TI  - Assembly of the intrinsic factor domains and oligomerization of the protein in
      the presence of cobalamin.
AB  - Human intrinsic factor (IF) was purified from the recombinant plant Arabidopsis
      thaliana by affinity chromatography. Cobalamin (Cbl) saturated protein was
      separated by gel filtration into peaks I and II, which contained according to SDS
      electrophoresis the 50 kDa full-length protein IF(50) and a mixture of two
      fragments, respectively. Two components of peak II were identified as the 30 kDa
      N-terminal peptide IF(30) and the 20 kDa C-terminal glycopeptide IF(20).
      Measurements of M(w) under the nondenaturing conditions were conducted by static
      light scattering. They revealed 100 kDa IF dimers in peak I, whereas 50 kDa
      cleaved monomers were found in peak II. The protein devoid of Cbl dissociated to
      the elementary units incapable of association in the absence of Cbl. The
      individual proteolytic fragments bound Cbl at high concentration of the ligand;
      however, neither IF(30).Cbl nor IF(20).Cbl oligomerized. A mixture of two
      fragments IF(30) + IF(20) and Cbl produced a firm complex, IF(30+20).Cbl, which
      could not associate to dimers. In contrast to IF(30+20).Cbl, the saturated full
      length monomers IF(50).Cbl dimerized with K(d) approximately 1 microM. We suggest
      a two-domain organization of the full-length protein, where two distant units,
      IF(30) and IF(20), can be assembled only by Cbl. They are connected by a protease
      sensitive link, whose native structure is likely to be important for
      dimerization. However, linkage between two domains is not compulsory for Cbl
      binding. Advantages of the two-domain structure of IF are discussed.

PMID- 15554719
TI  - Angiotensin antagonism in patients with heart failure: ACE inhibitors,
      angiotensin receptor antagonists or both?
AB  - Chronic heart failure (CHF) is a major cause of morbidity and mortality in
      western society. It is now widely accepted that the renin-angiotensin-aldosterone
      system (RAAS) and, in particular, angiotensin II (A-II) play a key role in the
      pathophysiology of CHF. Large-scale clinical trials have demonstrated that
      inhibitors of angiotensin-converting enzyme (ACE), the principal enzyme
      responsible for A-II production, improve symptoms and survival in patients with
      CHF. This enzyme is also responsible for the breakdown of the vasodilator hormone
      bradykinin. Administration of ACE inhibitors is associated with increased plasma
      bradykinin levels and this is thought to contribute to the vascular changes
      associated with ACE inhibitor therapy. However, RAAS inhibition with ACE
      inhibitors remains incomplete because ACE inhibitors do not block the non-ACE
      mediated conversion of angiotensin I to A-II. Angiotensin receptor antagonists
      (angiotensin receptor blockers; ARBs) antagonize the action of A-II at the A-II
      type 1 (AT(1)) receptor, whilst allowing the potentially beneficial actions of A
      II mediated via the A-II type 2 (AT(2)) receptor. Evidence that the clinical
      benefit demonstrated with ACE inhibitors in patients with CHF may extend to ARBs
      has only emerged recently. Combination therapy with both an ACE inhibitor and an
      ARB has a number of potential advantages and has been investigated in several
      large-scale clinical trials recently. In patients with CHF, first-line therapy
      should include an ACE inhibitor and a beta-adrenoceptor antagonist. The addition
      of an ARB provides symptomatic relief but has not been shown to improve survival.
      Where an ACE inhibitor is not tolerated, treatment with an ARB would seem an
      appropriate alternative. There is insufficient data to support the routine use of
      ARBs as first-line therapy in the management of CHF.

PMID- 15554720
TI  - Paclitaxel-eluting stents: current clinical experience.
AB  - In the past few years, drug-eluting stents have emerged as one of the most
      promising technologies in the field of interventional cardiology. Loaded with
      antiproliferative and anti-inflammatory agents, these stents have the potential
      to reduce post-stent-implantation restenosis significantly. In particular,
      sirolimus- and paclitaxel-eluting stents (PES) have been shown to be remarkably
      effective and are now available commercially in many countries.However, several
      PES systems have been under clinical investigation and produced different
      outcomes because of differences in their stent platforms, their total drug load,
      and their drug delivery and release concepts. The multicenter studies ASPECT
      (Asian Paclitaxel-Eluting Stent Clinical Trial), ELUTES (European evaLUation of
      PacliTaxel-Eluting Stent), and DELIVER (the RX Achieve drug-eluting coronary
      stent system in the treatment of patients with de novo native coronary lesions) I
      and II have been conducted to evaluate a PES system with direct impregnation of
      the agent onto the stent surface without using any further coatings. ASPECT and
      ELUTES revealed a clear dose response with descending binary restenosis rates for
      ascending drug dosages. However, statistically significant reductions of
      neointimal proliferation were only observed in the high-dose groups. DELIVER I, a
      study including 1043 patients, demonstrated the safety of the directly paclitaxel
      coated RX Achieve stent, but the late loss reduction did not translate into a
      sufficient reduction of the clinical endpoints. The TAXUS program has been
      conducted to explore safety and efficacy of the TAXUS polymer-based, PES system,
      which delivers polymer-controlled low-dose paclitaxel, in contrast to the stents
      with direct impregnation. TAXUS I, a randomized trial with 61 patients, revealed
      the first evidence of the potential of this concept with remarkable results in
      safety and reduction of in-stent restenosis. In a larger patient population, the
      following TAXUS II trial demonstrated the safety and superior performance of the
      TAXUS-slow and TAXUS-moderate release stents over uncoated control stents for the
      reduction of restenosis up to 12 months after implantation. TAXUS IV, the pivotal
      US multicenter study including 1314 patients, underlined the efficacy of this
      stent in a wide range of complex patient and lesion subsets, including small
      vessels, long lesions, and diabetes mellitus. The ongoing TAXUS V and VI trials
      are designed to show whether this benefit will be reproducible in even more
      complex lesion subsets. Beside these randomized studies, several 'real-world'
      registries have recently been started to evaluate the performance of the TAXUS
      stent in daily clinical practice. Programs like these are vital to sufficiently
      monitor patients who have received a drug-eluting stent, particularly because of
      the controversy regarding long-term effects.

PMID- 15554721
TI  - Therapeutic effects of angiotensin (AT1) receptor antagonists: potential
      contribution of mechanisms other than AT1 receptor blockade.
AB  - Blockade of the renin-angiotensin system improves morbidity and mortality of
      patients with cardiovascular diseases, e.g. arterial hypertension, renal failure,
      following myocardial infarction and in congestive heart failure. The angiotensin
      II type 1 (AT(1)) receptor antagonists (angiotensin receptor blockers; ARBs),
      i.e. losartan, eprosartan, irbesartan and valsartan were developed by computer
      based molecule design. Early observations already indicate that the ARBs elicit
      pleiotropic effects developing anti-aggregatory, anti-inflammatory and anti
      mitogenic effects independent from their actions at the AT(1) receptor. Losartan
      metabolism indicates a number of known active intermediates and pointed to
      further interactions of these derivatives with other receptors and cellular
      signaling systems. Here we discuss a compilation of detailed pharmacokinetic and
      pharmacodynamic data of active metabolites of ARBs indicating their mode of
      action and suggest novel therapeutic implications. The clinical observations that
      ARBs elicit potencies in patients with cardiovascular diseases via the regulation
      of inflammatory, growth and homeostatic factors lead us to focus on specific,
      reactive metabolites, which hold potential for future indications and possible
      drug interactions in cardiovascular diseases.

PMID- 15554722
TI  - Reversal of left ventricular hypertrophy: what have recent trials taught us?
AB  - Regression of left ventricular hypertrophy (LVH) is an important intermediate
      target for antihypertensive therapy. Thus, several trials and meta-analyses have
      attempted to compare the effects of different antihypertensive agents on LVH, but
      flawed study designs and methodologic problems have limited the utility of these
      studies. PRESERVE (Prospective Randomized Enalapril Study Evaluating Regression
      of Ventricular Enlargement), LIVE (LVH: Indapamide Sustained Release Versus
      Enalapril) and LIFE (Losartan Intervention For Endpoint reduction in
      hypertension) represent a new generation of large well designed trials with the
      power to compare different antihypertensive drugs. These studies have shown that
      treatment regimens based on enalapril and a nifedipine gastrointestinal
      therapeutic system are of similar efficacy (PRESERVE), that indapamide sustained
      release (SR) is superior to enalapril (LIVE), and that a regimen based on
      losartan is superior to a regimen based on atenolol (LIFE) in reversing
      hypertensive LVH. LIVE incorporated on-treatment echocardiographic quality
      control, with centralized readers blinded for both treatment and sequence of
      recording. The findings of these rigorous studies, to some extent in disagreement
      with results of previous meta-analyses, support the notion that antihypertensive
      drugs need to be judged on their individual effects on important intermediate
      endpoints such as LVH in well designed and adequately sized studies. However,
      extrapolation of the results of these studies in terms of class effects could be
      misleading and should be made with caution.

PMID- 15554723
TI  - Clinical and experimental experience with factor Xa inhibitors.
AB  - Cardiovascular disease is the major cause of mortality in the industrial world
      today. We are constantly moving towards new and better ways of fighting this
      epidemic. Advances have been made in various fields such as patient education,
      imaging techniques, interventional cardiology, and novel therapeutic agents. In
      particular, antithrombotics are being studied with great interest and hope. Amid
      this class of agents, factor Xa inhibitors have already begun to show promising
      results in trials involving patients with acute coronary syndromes. Whereas DX
      9065a is in late stage clinical trials, fondaparinux sodium is available for
      clinical use. Promising results have been obtained with fondaparinux sodium in
      patients with coronary artery disease in the PENTUA (Pentasaccharide in Unstable
      Angina) and PENTALYSE (Pentasaccharide as an Adjunct to Fibrinolysis in ST
      Elevation Acute Myocardial Infarction) trials. Besides having a direct effect on
      the coagulation cascade, they have shown properties that indirectly influence the
      remodeling of plaques in the coronary circulation. Available evidence on factor
      Xa inhibitors does not ensure a remedy to acute coronary syndromes but it gives
      hope of improving current treatments and reducing the morbidity and mortality of
      cardiovascular disease. The efficacy and tolerability of fondaparinux sodium in
      the prevention and treatment of deep vein thrombosis (with or without pulmonary
      embolism) has been established in several large trials such as PENTATHLON
      (Pentasaccharide in Total Hip Replacement Surgery), PENTAMAKS (Pentasaccharide in
      Major Knee Surgery), EPHESUS (European Pentasaccharide Hip Elective Surgery),
      PENTHIFRA (Pentasaccharide in Hip-Fracture Surgery), and PENTHIFRA-Plus. Whereas
      fondaparinux sodium offers benefits over low molecular weight heparins and
      unfractionated heparin, the incidence of bleeding complications was greater with
      fondaparinux sodium than with unfractionated heparin. Treatment with factor VIIa
      can reverse the anticoagulant effect of fondaparinux sodium and this may be
      particularly important in patients who need to undergo emergency surgical
      procedures. Fondaparinux sodium has been recently approved for use, in
      conjunction with warfarin, in patients with symptomatic deep vein thrombosis or
      acute pulmonary embolism based on the results of two large trials conducted by
      the Matisse investigators. In conclusion, these observations strongly suggest the
      clinical potential of this class of agents in preventing arterial and venous
      thrombosis.

PMID- 15554724
TI  - Intravascular brachytherapy: indications and management of adverse events.
AB  - Intravascular brachytherapy has become the standard of care for the treatment of
      coronary in-stent restenosis after repeat angioplasty. More than 5000 patients
      have been treated as part of various clinical trials. Based on the results of the
      GAMMA I trial, the START ((90)Sr Treatment of Angiographic Restenosis Trial), and
      the INHIBIT (INtimal Hyperplasia Inhibition with Beta In-stent restenosis Trial),
      the Checkmate system using (192)Ir, the Betacath system using (90)Sr/Y, and the
      Galileo system using (32)P, have been approved for the treatment of in-stent
      restenosis. With a better understanding and application of radiation oncology
      concepts to vascular brachytherapy, problems such as edge failure are being
      overcome. The complication of late thrombosis has also become less significant
      with the elimination of restenting at the brachytherapy procedure, and the
      prolonged use of antiplatelet therapy. There are other competing modalities in
      the early phases of clinical trials. The durability of results, lack of any
      significant long-term complications and the confirmation of the efficacy in other
      sites will further consolidate the role of radiation in treating in-stent
      restenosis.

PMID- 15554725
TI  - Valsartan: a review of its use in patients with heart failure and/or left
      ventricular systolic dysfunction after myocardial infarction.
AB  - Valsartan (Diovan) is an oral angiotensin II-receptor antagonist with specificity
      for the angiotensin II type 1 receptor subtype. It demonstrates antihypertensive
      activity and slows the progression of chronic heart failure (CHF). Recently it
      has been evaluated in comparison with an ACE inhibitor regimen in patients with
      heart failure or left ventricular systolic dysfunction (LVSD) after an acute
      myocardial infarction (MI), a population known to be at high risk of subsequent
      death or other major cardiovascular events. In the VALIANT (VALsartan In Acute
      myocardial iNfarcTion) trial, valsartan was as effective as captopril at reducing
      mortality and cardiovascular morbidity in patients who developed heart failure
      and/or LVSD after surviving an MI. It was also generally well tolerated in this
      population. Treatment with a combination of valsartan plus captopril provided no
      additional therapeutic benefit over treatment with captopril and was less well
      tolerated. Valsartan has a potential role as a new treatment for high-risk
      patients in the post-MI setting.

PMID- 15554726
TI  - Ezetimibe/Simvastatin: a review of its use in the management of
      hypercholesterolemia.
AB  - Ezetimibe/simvastatin (Inegy, Vytorin) therapy combines two lipid-lowering
      compounds with complementary mechanisms of action, thereby blocking the two
      sources of plasma cholesterol and improving lipid profiles. Thus, intestinal
      absorption of dietary cholesterol and related phytosterols is blocked by
      ezetimibe, with the biosynthesis of cholesterol in the liver inhibited by
      simvastatin. Developing management trends for primary hypercholesterolemia
      include the aggressive reduction of low-density lipoprotein cholesterol (LDL-C)
      to goals lower than previously considered appropriate, the targeting of lipid
      subfractions and atherogenic indices other than LDL-C alone, and the broader use
      of combination lipid-lowering therapy. In line with these trends,
      ezetimibe/simvastatin is an effective and generally well tolerated adjunct to
      dietary therapy for markedly reducing LDL-C levels, providing a 52% reduction
      with the recommended starting dosage. Furthermore, ezetimibe/simvastatin is
      formulated with variable doses of simvastatin (i.e. 10/10 mg, 10/20 mg, 10/40 mg,
      and 10/80 mg) and hence, the dosage may be adjusted to suit the individual
      patient's needs. As longer-term efficacy, tolerability, economic and outcome data
      accrue, ezetimibe/simvastatin will be positioned more definitively relative to
      existing and emerging lipid-lowering treatments. Currently, ezetimibe/simvastatin
      therapy represents a valuable novel option for the management of primary
      hypercholesterolemia across diverse patient populations and as an adjunct to
      other lipid-lowering treatments in those with homozygous familial
      hypercholesterolemia.

PMID- 15554728
TI  - Cardiac syndrome x: diagnosis, pathogenesis and management.

PMID- 15554729
TI  - The potential role of allergen-specific sublingual immunotherapy in atopic
      dermatitis.
AB  - Atopic dermatitis is a chronic inflammatory skin disease associated with
      increasing prevalence, morbidity, and cost in developed Western countries.
      Frequently associated with respiratory allergy during adulthood, atopic
      dermatitis often represents the first phenotypic appearance of atopy in early
      childhood when the allergic 'march' starts and progressively moves toward food
      allergy, asthma, and rhinitis. At present, a consistent body of evidence supports
      the view that atopic dermatitis may represent the skin compartmentalization of a
      systemic allergic inflammation. Lymphocytes infiltrating early lesional skin
      express a T helper (Th) 2 pattern of cytokine secretion (increased levels of
      interleukin [IL]-4 and/or IL-13 and decreased levels of interferon-gamma) as well
      as the typical Th2-type chemokine receptor CCR4, specific to the thymus and
      activation-regulated chemokines. Keratinocytes from patients with atopic
      dermatitis produce thymic stromal lymphopoietin, a novel cytokine that supports
      the early lymphocyte development in mouse models, and activates dendritic cells
      involved in the pathogenesis of allergic diseases in humans. Increased levels of
      circulating hemopoietic precursor cells have been reported in atopic dermatitis,
      as in allergic asthma and rhinitis. Furthermore, the recognition of CD34+
      hemopoietic precursor cells, and evidence for cellular
      differentiation/maturational events occurring within atopic dermatitis skin
      lesion infiltrates, are consistent with the recent reinterpretation of the
      Th2/Th1 paradigm, where Th2 cells appear to belong to the early stages and Th1 to
      the ultimate stages of a linear, rather than divergent, pattern of lymphoid
      differentiation. This more detailed understanding of the immunologic derangements
      contributing to the atopic dermatitis pathogenesis has led to growing interest in
      allergen-specific immunotherapy for the disease. Due to the complexity intrinsic
      to atopic dermatitis and the lack of consensus-based guidelines for standardized
      outcome measure, only eight studies are available in the literature for a
      qualitative evaluation of this treatment approach. Two of these studies were
      double blind and placebo controlled, and six were cohort studies. Immunotherapy
      was found to be effective in one controlled study and five observational reports.
      Uncertain results were provided by one low-powered, controlled study, and
      negative outcomes were raised by a unique study performed with oral
      immunotherapy, which is not an effective route of mucosal allergen
      administration. Thus, more efficacy studies are required before immunotherapy
      could be recommended for the routine treatment of atopic dermatitis. Allergen
      specific sublingual immunotherapy, given its excellent safety profile and ability
      to interfere with the systemic aspects of allergic inflammation, appears a good
      potential candidate for the pathogenetic treatment of the disease.

PMID- 15554730
TI  - Effects of airbag deployment: lesions, epidemiology, and management.
AB  - Airbags are restraining safety devices, but their activation may sometimes induce
      injuries during road accidents. Rapid deceleration due to an impact causes the
      ignition of a sodium azide cartridge, which releases nitrogen gas to inflate the
      nylon rubber bag. Numerous high-temperature gases, sodium hydroxide, carbon
      dioxide, and various other metallic oxides are also released producing a
      corrosive alkaline aerosol. Cutaneous and extracutaneous injuries due to airbag
      deployment may occur. Cutaneous injuries are frequent, and consist of irritant
      dermatitis, and chemical and thermal burns. Furthermore, numerous kinds of
      traumatic lesions (abrasions, friction burns, and lacerations) may be observed.
      Extracutaneous damage may involve the eyes, ears, cardiovascular system, nerves,
      joints, and bones. The nature of airbag lesions, their frequency, and management
      are reported. Even though the majority of airbag lesions are minor and do not
      require hospitalization, correct diagnosis and the choice of the most suitable
      treatment are necessary.

PMID- 15554731
TI  - Folliculitis: recognition and management.
AB  - Folliculitis is an inflammatory reaction in the superficial aspect of the hair
      follicle and can involve the follicular opening or the perifollicular hair
      follicles. The pilosebaceous unit of the follicle is divided into three
      compartments: the infundibulum (superficial part, outlined by the sebaceous
      duct), the isthmus (between the sebaceous duct and arrector pili protuberance),
      and the inferior segment (stem and hair bulb). This anatomical scheme forms the
      basis for any evaluation of the clinical manifestations of folliculitis. Most of
      the follicular conditions can be classified according to their anatomical
      location and histopathologic patterns. Clinically, the inflammation manifests as
      1mm-wide vesicles, pustules, or papulopustules in acute cases; however,
      hyperkeratosis and keratotic plug formations are indicative of a chronic process.
      The presence of superficial pustules does not always imply an infectious origin,
      as there are many noninfectious types of folliculitis. In this review, we
      describe the different types of folliculitis based on their etiology, clinical
      manifestation, and treatment. We also discuss some newly described disorders and
      the latest information on their treatment.

PMID- 15554732
TI  - Management of cutaneous warts: an evidence-based approach.
AB  - Cutaneous warts are benign epidermal proliferations caused by human
      papillomavirus infection. Treatment aims to cure the patient's physical and
      psychological discomfort, and to prevent the spread of infection by contact with
      other body areas or with other individuals. Among the available medical and
      destructive therapeutic options for cutaneous warts, none is uniformly effective
      or virucidal. Moreover, in most cases the safety and efficacy of these treatment
      options has not been assessed in randomized controlled trials, so that the
      reproducibility of many of the listed treatments is difficult to evaluate and a
      possible placebo effect cannot be ruled out. This article provides indications
      for the management of patients with cutaneous warts through an evidence-based
      approach, considering a first-, second-, and third-line therapy for each clinical
      form. The first line includes medical treatments useful to cure single, or few,
      and/or small common warts of short duration (<1 year). If these treatments have
      failed or are contraindicated, cryotherapy may be considered as second-line
      therapy. For recurrent or difficult-to-treat lesions, a third-line of therapy
      includes a variety of alternative therapeutic options that are in clinical use
      but are not necessarily approved by the US FDA, and their use may be further
      limited by adverse effects.

PMID- 15554733
TI  - Management of bullous pemphigoid: recommendations for immunomodulatory
      treatments.
AB  - In 1953, Lever differentiated bullous pemphigoid from autoimmune pemphigus. The
      natural course of bullous pemphigoid is relatively benign, with a disease-related
      mortality rate of 24% compared with around 70% in pemphigus. In spite of the
      introduction of systemic corticosteroids, the mortality rates in bullous
      pemphigoid have generally not improved and vary between 0% and 40%. Higher doses
      of systemic corticosteroids seem to be associated with higher mortality rates,
      which led to the addition of corticosteroid-sparing agents to the treatment of
      bullous pemphigoid. However, many of these modalities are also accompanied by
      severe adverse effects and have not led to a significant decrease in the
      mortality rate. In recent years, there has been a move toward less toxic
      treatment options for a disease that is usually self-limited. A systematic review
      of the literature found that treatment with lower doses of systemic
      corticosteroids and potent topical corticosteroids is effective and accompanied
      by less serious adverse effects, including death. No benefit of the addition of
      plasmapheresis or azathioprine to systemic corticosteroids has been shown. The
      treatment of bullous pemphigoid with tetracyclines and niacinamide (nicotinamide)
      is effective and accompanied by less serious adverse effects. However, more
      randomized controlled trials are needed to confirm these results and to determine
      the best treatment for bullous pemphigoid.

PMID- 15554734
TI  - Cosmetic allergy: incidence, diagnosis, and management.
AB  - A recent epidemiologic survey in the UK revealed that 23% of women and 13.8% of
      men experience some sort of adverse reaction to a personal care product over the
      course of a year. Although most of these reactions may be due to subjective
      sensory irritation, various studies reveal that up to 10% of dermatologic
      patients who are patch tested are allergic to cosmetic products or their
      constituent ingredients. Causative products include deodorants and perfumes, skin
      care products, hair care products, and nail cosmetics. Allergic contact
      dermatitis mainly results from fragrance chemicals and preservatives. Recent work
      has suggested that additional fragrance chemicals may need to be tested in order
      to identify those patients 'missed' by the current fragrance mix; in particular,
      hydroxy-isohexyl-3-cyclohexene carboxaldehyde (HMPPC Lyral) has been singled out
      as an important sensitizing agent. The increased usage of natural fragrances and
      botanic extracts can also cause problems in their own right or through co
      reactivity. The preservative methyldibromo glutaronitrile has also been
      recognized as an increasingly important sensitizer in Europe, which has led to
      the recent recommendation that it should be prohibited from 'leave-on' products
      until information on 'safe' consumer levels becomes available. Other emerging
      allergens include UV filters, tosylamide/formaldehyde resin, and nail acrylates.
      The diagnosis of cosmetic allergy should be confirmed with patch testing,
      including testing of 'whole' products, when necessary, and repeat open
      application tests can be used to confirm the relevance of reactions in cases of
      doubt.

PMID- 15554735
TI  - Pimozide in dermatologic practice: a comprehensive review.
AB  - Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. In the
      US, it is FDA-approved only as a backup treatment for Gilles de la Tourette
      syndrome, although it has been used in other countries for many years as a
      treatment for schizophrenia. In the past 20 years, pimozide has been found to be
      especially efficacious in the treatment of monosymptomatic hypochondriacal
      psychoses and is used by psychiatrists and dermatologists for this off-label
      purpose. In particular, pimozide is considered the treatment of choice for
      delusions of parasitosis. In addition, pimozide has been found to be efficacious
      in the treatment of body dysmorphic disorder, metastatic melanoma,
      trichotillomania, and trigeminal and postherpetic neuralgia. This review aims to
      familiarize physicians, especially dermatologists, on the uses of pimozide in
      dermatologic practice. A review of the literature was performed and the relevant
      information synthesized to give a complete overview of the drug and its
      therapeutic uses in dermatology.

PMID- 15554736
TI  - Sympathomimetic drug allergy: cross-reactivity study by patch test.
AB  - INTRODUCTION: Sympathomimetic (alpha-adrenergic) drugs are mainly used because of
      their vasoconstrictor properties, for nasal congestion, or as mydriatics.
      Although sympathomimetic drugs are used often, allergic reactions are rare,
      especially when the drugs are administered systemically. Cross-reactivity may
      exist among catecholamine derivatives, although reported data on this are
      contradictory. In this study, we investigate if there is cross-reactivity in
      patch tests among these drugs. MATERIAL AND METHODS: Patch tests with 10%
      phenylephrine and 10% pseudoephedrine in petrolatum, and 10% and 20% ephedrine,
      10% phenylpropanolamine, 5% fepradinol, 1% methoxamine, and 10% oxymetazoline,
      all administered in dimethyl sulfoxide (DMSO), were carried out in 14 patients
      with a history of allergy to any of these drugs. DMSO was used as the negative
      control. RESULTS: All patients except one (patient number five) showed positive
      patch-test reactions to at least two different drugs. Nine patients (64.3%) were
      cross-sensitized to three or more different drugs, and 57.1% of patients were
      sensitized to four or more sympathomimetic drugs. Patients who experienced
      generalized rashes caused by orally administered pseudoephedrine had a stronger
      response and more cross-reactivity with other sympathomimetic drugs in patch
      tests than those who experienced local contact dermatitis. CONCLUSIONS: We
      conclude that there is cross-reactivity among the different sympathomimetic drugs
      tested, especially if the drug is administered systemically.

PMID- 15554737
TI  - Localized panniculitis and subsequent lipoatrophy with subcutaneous glatiramer
      acetate (Copaxone) injection for the treatment of multiple sclerosis.
AB  - Glatiramer acetate (copolymer 1, Copaxone) is a mixture of synthetic polypeptides
      and is used for the treatment of multiple sclerosis. It has been shown to possess
      beneficial effects in reducing the relapse rate in relapsing-remitting multiple
      sclerosis. Its main mechanism of action is regarded as a switch of the immune
      reaction from a T helper (Th)1 to a Th2 cell type. Glatiramer acetate is
      administered by subcutaneous injection once daily. As described in previous
      reports, the most common adverse effects are pain, inflammation, and induration
      at the injection site, occurring in approximately 20-60% of patients. A rare
      adverse effect is a localized lipoatrophy at the site of injection, which has
      previously been observed and described in 11 patients. It has been reported that
      these atrophic areas remain unchanged and localized lipoatrophy may be preceded
      by a subcutaneous panniculitis. In this article, we describe another case of
      subcutaneous changes following repeated glatiramer acetate injection, presented
      as localized panniculitis in the area around the injection sites, in a 46-year
      old female patient who was treated with glatiramer acetate for 18 months.

PMID- 15554738
TI  - Poly-L-lactic acid.
AB  - Poly-L-lactic acid, a synthetic biodegradable polymer, is available as an
      injectable intradermal implant for use in the correction and restoration of the
      signs of facial lipoatrophy in patients with HIV infection. In a 96-week
      noncomparative study in HIV-infected patients with severe facial lipoatrophy, 41%
      of patients treated with intradermal poly-L-lactic acid injections had a total
      cutaneous thickness of >10 mm at the nasogenian fold at week 24. Poly-L-lactic
      acid was injected into multiple sites of each cheek at baseline and at weeks 2,
      4, and 6. Significant (p < 0.001) increases from baseline in total cutaneous
      thickness were reported at all evaluation time points up to 96 weeks after the
      start of treatment. In a randomized, nonblind study, significant (p < 0.001)
      increases from baseline in dermal thickness were observed at week 24 in HIV
      infected patients with facial lipoatrophy who received immediate or deferred (by
      12 weeks) treatment with poly-L-lactic acid, administered by injection into
      multiple intradermal sites every 2 weeks (three injection sessions in total).
      Improvements in depression and anxiety scores, patient visual analog scale
      assessments, and photographic assessments were also reported in patients treated
      with poly-L-lactic acid in the immediate versus deferred treatment trial. Poly-L
      lactic acid was generally well tolerated. No serious adverse events were
      reported.

PMID- 15554742
TI  - Spotlight on adapalene in acne vulgaris.
AB  - Adapalene (Differin) is a retinoid agent indicated for the topical treatment of
      acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective
      in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin
      microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two
      days; however, the drug was less effective than once-daily 0.1% tazarotene gel.
      It can be used alone in mild acne or in combination with antimicrobials in
      inflammatory acne and has proved efficacious as maintenance treatment. Adapalene
      has a rapid onset of action and a particularly favorable tolerability profile
      compared with other retinoids. These attributes can potentially promote patient
      compliance, an important factor in treatment success. Adapalene is, therefore,
      assured of a role in the first-line treatment of acne vulgaris.

PMID- 15554743
TI  - Can we ensure the safe use of known human teratogens? Introduction of generic
      isotretinoin in the US as an example.
AB  - The prescription of known teratogenic medications requires a careful balance
      between allowing women access to medications that they might need and avoiding
      unnecessary exposure to these medications during pregnancy because of their
      devastating fetal effects. Isotretinoin, a potent human teratogen, is of
      particular concern because of its widespread use among reproductive-aged women
      and the dramatic increase in use from 1992 through 2000. A revised risk
      management system was implemented in 2002 because of concerns about the continued
      occurrence of isotretinoin-exposed pregnancies. However, the recent approval of
      three generic versions of isotretinoin in the US has further complicated risk
      management and raises concerns that use might increase further if the lower cost
      of generics serves to increase accessibility. There are now four separate
      isotretinoin risk management systems in the US, each with its own distinct
      packaging, though the requirements for and substance of each are identical. Some
      additional concrete steps could be taken to minimise any unnecessary use of
      isotretinoin and help allow an adequate assessment of the current risk management
      systems. In addition to being familiar with and following all aspects of the
      current risk management system, physicians could choose to limit the use of
      isotretinoin to those who meet the labelled indications in order to reduce the
      number of exposed pregnancies. All four companies currently marketing
      isotretinoin in the US could jointly and voluntarily establish a consolidated,
      mandatory registration and follow-up of all women of reproductive potential who
      receive an isotretinoin prescription. Mandatory registration has many challenges,
      but it could allow a clear accounting of the total number of women for whom
      follow-up information is and is not available. Although the companies cannot be
      legally compelled to use a consolidated approach, the use of a single registry
      for the originator's product and all generic brands would allow identification of
      duplicates and also avoid the confusion that is introduced by providing materials
      that not only look different, but also have different addresses, contact
      information and names for participation in follow-up surveys. This is
      particularly important because women might take more than one version of
      isotretinoin during a single course of therapy or might receive a different
      programme's materials from their doctor than from the pharmacy. Though the
      introduction of generic versions of isotretinoin further complicates risk
      management, the companies marketing isotretinoin have an opportunity to work
      together to demonstrate their commitment to both limit the occurrence of exposed
      pregnancies and conduct a meaningful evaluation of the occurrence of pregnancies
      exposed to isotretinoin.

PMID- 15554744
TI  - Overview of the tolerability of gefitinib (IRESSA) monotherapy : clinical
      experience in non-small-cell lung cancer.
AB  - Cytotoxic chemotherapy treatment options for patients with non-small-cell lung
      cancer (NSCLC) have limited efficacy and are often associated with significant
      toxicity. Therefore, there is an unmet need for novel drugs that are not only
      effective in treating this disease but are also well tolerated. Gefitinib is an
      orally active epidermal growth factor receptor tyrosine kinase inhibitor that
      blocks the signal transduction pathways implicated in cancer cell growth and
      survival. It has recently been approved for the treatment of advanced/refractory
      NSCLC. This review presents the tolerability data from phase I and II gefitinib
      monotherapy trials, along with data from the worldwide 'Expanded Access
      Programme' and post-marketing use of gefitinib. Gefitinib was found to be
      generally well tolerated at the approved dosage of 250 mg/day; the most commonly
      reported adverse drug reactions (ADRs) were mild to moderate skin rash and
      diarrhoea, which were manageable and non-cumulative. Other ADRs observed with the
      use of gefitinib included: dry skin, pruritus, acne, nausea, vomiting, anorexia,
      asthenia and asymptomatic elevations in liver transaminase levels. Well
      recognised adverse effects seen with cytotoxic chemotherapy (such as bone marrow
      depression, neurotoxicity and nephrotoxicity) were not observed. Although the
      frequency and severity of ADRs increased with the dosage across the range studied
      (50-1000 mg/day), few patients required dosage reductions or the withdrawal of
      treatment, and those who did usually received gefitinib >or=600 mg/day.Thus, the
      available data indicate that gefitinib is well tolerated in patients with a range
      of solid tumours, including locally advanced or metastatic NSCLC.

PMID- 15554745
TI  - Benefit-risk assessment of ropivacaine in the management of postoperative pain.
AB  - Ropivacaine is a long-acting amide-type local anaesthetic, released for clinical
      use in 1996. In comparison with bupivacaine, ropivacaine is equally effective for
      subcutaneous infiltration, epidural and peripheral nerve block for surgery,
      obstetric procedures and postoperative analgesia. Nevertheless, ropivacaine
      differs from bupivacaine in several aspects: firstly, it is marketed as a pure S(
      )-enantiomer and not as a racemate, and secondly, its lipid solubility is
      markedly lower. These features have been suggested to significantly improve the
      safety profile of ropivacaine, and indeed, numerous studies have shown that
      ropivacaine has less cardiovascular and CNS toxicity than racemic bupivacaine in
      healthy volunteers. Extensive clinical data have demonstrated that epidural 0.2%
      ropivacaine is nearly identical to 0.2% bupivacaine with regard to onset, quality
      and duration of sensory blockade for initiation and maintenance of labour
      analgesia. Ropivacaine also provides effective pain relief after abdominal or
      orthopaedic surgery, especially when given in conjunction with opioids or other
      adjuvants. Nevertheless, epidurally administered ropivacaine causes significantly
      less motor blockade at low concentrations. Whether the greater degree of blockade
      of nerve fibres involved in pain transmission (Adelta- and C-fibres) than of
      those controlling motor function (Aalpha- and Abeta-fibres) is due to a lower
      relative potency compared with bupivacaine or whether other physicochemical
      properties or stereoselectivity are involved, is still a matter of intense
      debate. Recommended epidural doses for postoperative or labour pain are 20-40 mg
      as bolus with 20-30 mg as top-up dose, with an interval of >or=30 minutes.
      Alternatively, 0.2% ropivacaine can be given as continuous epidural infusion at a
      rate of 6-14 mL/h (lumbar route) or 4-10 mL/h (thoracic route). Preoperative or
      postoperative subcutaneous wound infiltration, during cholecystectomy or inguinal
      hernia repair, with ropivacaine 100-175 mg has been shown to be more effective
      than placebo and as effective as bupivacaine in reducing wound pain, whereby the
      vasoconstrictive potency of ropivacaine may be involved. Similar results were
      found in peripheral blockades on upper and lower limbs. Ropivacaine shows an
      identical efficacy and potency to that of bupivacaine, with similar analgesic
      duration over hours using single shot or continuous catheter techniques. In
      summary, ropivacaine, a newer long-acting local anaesthetic, has an efficacy
      generally similar to that of the same dose of bupivacaine with regard to
      postoperative pain relief, but causes less motor blockade and stronger
      vasoconstriction at low concentrations. Despite a significantly better safety
      profile of the pure S(-)-isomer of ropivacaine, the increased cost of ropivacaine
      may presently limit its clinical utility in postoperative pain therapy.

PMID- 15554746
TI  - Fab antibody fragments: some applications in clinical toxicology.
AB  - This review provides current information on the use of antigen-binding fragments
      (Fab) from cleaved antibodies to treat poisoning with digoxin and other potent,
      low formula mass poisons, such as colchicine and tricyclic antidepressants. Anti
      digoxin Fab fragments have been used successfully for many years in the
      management of severe poisoning with digoxin, digitoxin, and a range of other
      structurally related compounds, including cardiotoxins from Nerium and Thevetia
      sp. (oleander) and Bufo sp. (toads). However, their main use remains treating
      digoxin poisoning. Equimolar doses of anti-digoxin Fab fragments completely bind
      digoxin in vivo. The approximate dose of Fab fragments (mg) is 80 times the
      digoxin body burden (mg). If neither the dose ingested nor the plasma
      digoxin/digitoxin concentration is known, in an adult 380 mg of anti-digoxin Fab
      fragments should be given. The dose for elderly patients or those with renal
      impairment should be similar to that for those with normal renal function. Fab
      fragments have a plasma half-life of 12-20 hours, but this can be prolonged in
      patients with renal impairment. Analysis of serum ultrafiltrate using an
      immunoassay shown not to have matrix bias remains the most accurate approach to
      measuring free digoxin in the presence of anti-digoxin Fab fragments. The
      antibody fragments are given intravenously over 15-30 minutes after dilution to
      at least 250 mL with plasma protein solution, 0.9% (w/v) sodium chloride, or
      deionised water, except in infants where the volume infused can be reduced.
      Factors limiting the efficacy of Fab fragments are the dose, the duration of the
      infusion and any delay in administration. Guidelines for Fab fragment
      administration in children include (i) dilution to a final Fab concentration of
      10 g/L in either 5% (w/v) dextrose or 0.9% (w/v) sodium chloride; (ii) infusion
      through a 0.22 microm filter; (iii) administration of the total dose over a
      minimum of 30 minutes; and (iv) avoiding coadministration of other drugs and/or
      electrolyte solutions. Fab fragments are generally well tolerated. Adverse
      effects attributable to Fab treatment include hypokalaemia and exacerbation of
      congestive cardiac failure; renal function could be impaired in some patients.
      Fab fragment preparations for treating acute colchicine and tricyclic
      antidepressant poisoning have been developed, but are not available commercially.
      Colchicine poisoning is rare in Western countries, and pharmacological management
      together with supportive care is usually effective even in severe tricyclic
      antidepressant overdosage. Attempts have been made to produce anti-paraquat
      antibodies capable of enhancing paraquat elimination from the lung, but thus far
      all such attempts have proved unsuccessful.

PMID- 15554747
TI  - Benefit-risk assessment of atypical antipsychotics in the treatment of
      schizophrenia and comorbid disorders in children and adolescents.
AB  - Evidence on the efficacy and safety of atypical antipsychotics in children and
      adolescents with schizophrenia is limited. The purpose of this review is to
      assess the published data on the use of atypical antipsychotics in children and
      adolescents with schizophrenia alone and with comorbid disorders, and to
      establish benefit-risk guidelines for clinicians.Risperidone, olanzapine and
      clozapine were found to be effective in the treatment of aggression and mania.
      Risperidone, and possibly also olanzapine, may be the drugs of choice in children
      with comorbid tic disorders. Ziprasidone has some monoamine reuptake inhibition
      properties and may be administered as an augmenting agent in children and
      adolescents with schizophrenia and comorbid anxiety and mood disorders. Compared
      with the typical antipsychotics, the atypical drugs seem to be more effective,
      better tolerated and lead to better patient adherence. Importantly, the atypical
      antipsychotics have a lower propensity to induce extrapyramidal symptoms and a
      potential (shown so far only in adults) to improve cognitive function and inhibit
      suicidal behaviour (especially clozapine). Yet, the adverse effects associated
      with these agents, especially weight gain, which may also have long-term effects,
      can lead to non-compliance in the young population. In children and adolescents
      receiving clozapine, olanzapine and quetiapine (but not ziprasidone, which does
      not have a pro-appetite effect), particularly those with obesity or a family
      history of diabetes mellitus, fasting blood glucose and lipid levels must be
      monitored frequently. Weight gain might be better controlled when the children
      and their parents are properly informed about this adverse effect and diet is
      regulated. Another major disadvantage of the atypical antipsychotics, especially
      risperidone, is their association with hyperprolactinaemia, which can lead to
      hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular
      menstruation and sexual dysfunction, all seen also with typical antipsychotics.
      Other atypical antipsychotics, namely olanzapine and ziprasidone, have been
      reported to be prolactin sparing in adults, but may not be completely devoid of
      hyperprolactinaemic effects in children and adolescents. Thus, prolactin levels
      should be assessed routinely in young patients treated with atypical
      antipsychotics. Further, children and adolescents with hyperprolactinaemia
      related effects should be switched to a prolactin-sparing agent, such as
      quetiapine. All atypical antipsychotics may induce sedation and they are not
      devoid of extrapyramidal symptoms (especially risperidone). The use of typical
      antipsychotics has been limited to patients who are resistant to atypical
      antipsychotics, intolerant to their adverse effects, or require injections or
      depot preparations. Further double-blind, placebo-controlled trials and long-term
      safety assessments are needed before definitive conclusions can be reached about
      the place of atypical antipsychotics in the therapeutic armamentarium of
      childhood-onset schizophrenia.

PMID- 15554748
TI  - Current use of selective serotonin reuptake inhibitors and risk of acute
      myocardial infarction.
AB  - BACKGROUND: It has been suggested that increased platelet activation increases
      the risk of acute myocardial infarction (AMI) in patients with depression.
      Selective serotonin reuptake inhibitors (SSRIs) may attenuate platelet activation
      by serotonin depletion in platelets. Observational studies have shown discrepant
      results of AMI risk associated with the use of SSRIs. OBJECTIVE: The aim of this
      study was to evaluate the association of exposure to different groups of
      antidepressants, including SSRIs, and the risk of AMI. The study also assessed in
      more detail the influence of timing of the exposure to antidepressants in a
      general adult population (<90 years of age), with or without diagnosed risk
      factors for AMI. STUDY DESIGN/METHODS: We conducted a population-based case
      control analysis on the UK General Practice Research Database (GPRD). The study
      included 8688 patients (<90 years of age), with a first-time AMI between 1995 and
      2001, and 33 923 controls, who were matched by age, sex, calendar time, and
      general practice. Conditional logistic regression was used to estimate odds
      ratios (ORs). RESULTS: Current use of an antidepressant was defined as a supply
      of the last prescription for an antidepressant that lasted up to the index date
      or beyond. Recent past use was defined as a supply of the last prescription for
      an antidepressant that ended 1-29 days before the index date. SSRIs investigated
      were citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine.
      Non-SSRIs investigated were amitriptyline, clomipramine, dosulepin, doxepin,
      imipramine, lofepramine, nefazodone, trazodone and trimipramine. Other
      antidepressants included were amoxapine, desipramine, lithium, maprotiline,
      mianserin, moclobemide, nortriptyline and protriptyline. Adjusted ORs (with 95%
      CI) for the current use of SSRIs, non-SSRIs, or other antidepressants, compared
      with non-use of antidepressants, were 0.63 (95% CI 0.43, 0.91; p=0.02), 0.92 (95%
      CI 0.77, 1.09; p=0.32) and 0.59 (95% CI 0.29, 1.20; p=0.14), respectively. The
      adjusted OR of recent past use of SSRIs compared with non-use of SSRIs was 1.42
      (95% CI 1.02, 1.97; p=0.04). CONCLUSION: The present analysis provides further
      evidence that the current use of SSRIs is associated with a slightly decreased
      risk for AMI.

PMID- 15554749
TI  - Regional anaesthesia in the elderly: a clinical guide.
AB  - The number of elderly patients presenting for anaesthesia and surgery has
      increased exponentially in recent years. Regional anaesthesia is frequently used
      in elderly patients undergoing surgery. Although the type of anaesthesia (general
      versus regional anaesthesia) has no substantial effect on perioperative morbidity
      and mortality in any age group; it intuitively makes sense that elderly patients
      would benefit from regional anaesthesia because they remain minimally sedated
      throughout the procedures and awaken with excellent postoperative pain control.
      However, a multitude of factors influence the outcome, such as the type, duration
      and invasiveness of the operation, co-existing medical and mental status of the
      patient and the skill and expertise of the anaesthesiologist and surgeon. These
      factors make it difficult to decide if and when one technique is equivocally
      better than another. Thus, it is more important to optimise the overall
      management of the patient during the perioperative period and, in most cases, it
      is the quality of the anaesthetic administered rather than the type of
      anaesthetic which is most important. Sedatives used for regional anaesthesia in
      the elderly should be short acting, easy to administer, have a low adverse effect
      profile and high safety margin. Midazolam, lorazepam, ketamine, propofol and low
      dose opioids have been successfully used for sedation in the elderly. Aging
      affects the pharmacokinetics and pharmacodynamics of local anaesthetics,
      composition and characteristics of tissues and organs within the body, and
      physiological functions of the body. Changes in the systematic absorption,
      distribution and clearance of local anaesthetics lead to an increased
      sensitivity, decreased dose requirement and a change in the onset and duration of
      action in the elderly. Decreases in neural population, neural conduction velocity
      and inter-Schwann cell distance can lead to an increased sensitivity to local
      anaesthetics in the elderly. The addition of an opioid and epinephrine
      (adrenaline) has been shown to be useful in central neuraxial blockade.
      Epinephrine also can prolong the duration of peripheral nerve blocks. However,
      caution must be exercised as epinephrine has the potential for causing ischaemic
      neurotoxicity in peripheral nerves. Regional anaesthesia appears to be safe and
      beneficial in elderly patients; however, every anaesthetic administered must be
      assessed on a case-by-case basis and particular consideration should be given to
      the health status of the patient, the operation being performed and the expertise
      of the anaesthesiologist.

PMID- 15554750
TI  - The treatment of chronic constipation in elderly people: an update.
AB  - Constipation is a common problem in elderly persons, with prevalence ranging from
      15% to 20% in the community-dwelling elderly population and up to 50% in some
      studies of nursing home residents. In these patients, constipation results from a
      combination of risk factors, such as reduced fibre and fluid intake, decreased
      physical activity resulting from chronic diseases and multiple medications.
      Despite the high prevalence of constipation, there is surprisingly little
      evidence available on which to base management decisions of this common
      condition. Increased fluid intake, regular physical activity and high fibre
      intake are usually proposed as first step nonpharmacological measures. However,
      adherence to these measures is limited and pharmacological treatment is
      frequently required. Data are too limited, especially in elderly persons, to
      formally recommend one class of laxatives over another or one agent over another
      within each class. However, bulk-forming and osmotic laxatives are usually
      recommended as first-line agents, even though data on their effectiveness are
      limited. The need to maintain good hydration is a limitation in the use of bulk
      forming laxatives, in particular, in frail elderly patients. In these patients,
      polyethylene glycol, an osmotic agent, is an attractive alternative. In addition,
      it has been shown to relieve faecal impaction in frail patients with neurological
      disease. Its cost and potential danger in patients at high risk for aspiration
      is, however, a limitation. Stimulant laxatives are considered mainly as an
      intermittent treatment in patients who do not respond to bulk-forming or osmotic
      laxatives. Several promising compounds such as the new serotonin 5-HT4 receptor
      agonists (tegaserod, prucalopride) and neurotrophin-3 (NT3) have not been
      adequately tested in older individuals. They are not routinely used and their
      role in the management of constipation in these patients will be more precisely
      defined in the future. Other treatment options are available (acupuncture,
      biofeedback, botulinum toxin and surgery), but experience with these
      interventions in elderly patients is limited and their indications in this
      population remain to be clarified. Management of constipation in elderly persons
      depends largely on experience and beliefs. Several new compounds seem promising
      but will need to be specifically tested in this population before being
      recommended.

PMID- 15554751
TI  - Rivastigmine in frontotemporal dementia: an open-label study.
AB  - OBJECTIVE: This preliminary open-label study aims to investigate the effects of
      rivastigmine, an inhibitor of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE), in 20 patients diagnosed with frontotemporal
      dementia (FTD). PATIENTS AND METHODS: Study subjects were men and women 60-75
      years of age diagnosed with probable FTD. The rivastigmine group received doses
      of 3-9 mg/day. The control group included matched patients receiving
      antipsychotics, benzodiazepines and selegiline (deprenyl). All patients completed
      a 12-month follow-up period. RESULTS: Rivastigmine treatment was well tolerated.
      At 12 months, there was a general amelioration of behavioural changes as
      demonstrated by reductions in Neuropsychiatric Inventory (p<0.001 vs baseline and
      control), Behavioral Pathology in Alzheimer's Disease Rating Scale (p<0.001 vs
      baseline and control) and Cornell Scale for Depression in Dementia scores (p<0.05
      vs baseline, p<0.001 vs control) in the rivastigmine group. Caregiver burden was
      reduced, as shown by reduced Relative Stress Scale scores (p<0.001 vs baseline
      and control). Mean scores on outcome measures evaluating executive function
      stabilised in the rivastigmine group (p<0.05 vs controls). Rivastigmine did not
      prevent the disease-related deterioration of cognition as assessed using the Mini
      Mental State Examination. CONCLUSION: In this open-label study, rivastigmine
      treated patients were less behaviourally impaired, and caregiver burden was
      reduced, at 12 months, compared with baseline. The use of cholinesterase
      inhibitors in FTD warrants further research.

PMID- 15554752
TI  - Potentially inappropriate prescribing in Canada relative to the US.
AB  - OBJECTIVE: To explore the prescribing of potentially inappropriate drug therapy
      in Ontario, Canada where there is a restrictive drug formulary relative to the US
      where there is no single drug formulary. METHODS: A retrospective, cohort study
      using an administrative database (Ontario, Canada) compared with published survey
      results (US). All 1,088,680 community-dwelling adults >or=66 years of age in
      Ontario, Canada compared with published survey results from 2455 community
      dwelling older adults in the US in 1996. Patterns of potentially inappropriate
      drug prescribing were compared between countries using a list of 33 potentially
      inappropriate drug therapies. These therapies were classified by an expert panel
      into three categories: (i) those to always avoid; (ii) those which are rarely
      appropriate; and (iii) those with only some indications to prescribe. RESULTS:
      Among the 33 potentially inappropriate drug therapies, 15 (45%) prescribed in the
      US were not available through Ontario's drug formulary. Potentially inappropriate
      drug therapies available through the Ontario Drug Benefit Plan (ODB) and also in
      the US were frequently prescribed in both Ontario and the US. Differences in
      prescribing patterns of individual drug therapies were noted between the two
      countries. Specifically, in the rarely appropriate category, diazepam, a long
      half-life benzodiazepine, was much more frequently dispensed in Ontario than in
      the US (3.18% vs 1.37%). In contrast, dextropropoxyphene, an opioid with a poor
      adverse event profile was more frequently prescribed in the US than in Ontario
      (6.21% vs 0.74%). CONCLUSION: Almost half of the potentially inappropriate drug
      therapies that are available in the US are unavailable from Ontario's drug
      formulary. Potentially inappropriate drug therapies that were available through
      the ODB were frequently prescribed in both countries. Alternative approaches that
      make information immediately accessible to physicians at the time they make
      prescribing decisions should be considered to improve prescribing practices.

PMID- 15554753
TI  - Clodronate : a review of its use in the prevention of bone metastases and the
      management of skeletal complications associated with bone metastases in patients
      with breast cancer.
AB  - Clodronate (clodronate disodium, Bonefos) is a non-nitrogen-containing
      bisphosphonate that inhibits osteoclast activity, and thereby inhibits bone
      resorption. Clodronate has been extensively used in patients with advanced breast
      cancer, and is generally well tolerated. In patients with primary breast cancer,
      clodronate is currently the only bisphosphonate shown to improve survival rates
      and to reduce the incidence of bone metastases in randomised controlled trials.
      Further trials in patients with early breast cancer are warranted to confirm
      results to date and to determine the optimal duration of treatment, as well as
      the efficacy of the drug compared with other bisphosphonates. In the meantime,
      clodronate is a well established bisphosphonate which has shown beneficial
      effects in the prevention of bone metastases and on survival in patients with
      primary breast cancer.

PMID- 15554754
TI  - Prophylactic antipsychotics: do they keep you from catching schizophrenia?

PMID- 15554755
TI  - Metabolic effects of treatment with atypical antipsychotics.

PMID- 15554756
TI  - Antidepressants and suicide risk in the United States, 1985-1999.
AB  - BACKGROUND: The role of antidepressants in suicide prevention is a major public
      health question. An association was hypothesized between the increase in the use
      of non-tricyclic antidepressant medications in the United States and the decline
      in the suicide rate during the years 1985-1999. METHOD: The relationships between
      the suicide, antidepressant prescription, unemployment, and alcoholic beverage
      consumption rates were studied using generalized linear models. Suicide rates by
      antidepressant overdose were compared in selective serotonin reuptake inhibitors
      (SSRIs) and tricyclic antidepressants (TCAs). RESULTS: From 1985 to 1999, the
      suicide rate fell 13.5%, with a greater decline among women, and antidepressant
      prescription rates increased over 4-fold, with the increase mostly due to SSRIs.
      Prescription rates for SSRIs and other second-generation antidepressants were
      both inversely associated with suicide rates (p = .03 and p = .02, respectively).
      In a multivariable analysis adjusting for unemployment and alcoholic beverage
      consumption rates, SSRI antidepressant prescription rates remained inversely
      associated with the national suicide rate (p = .03). Females received twice as
      many antidepressant prescriptions compared with males. The commonest prescription
      indication was mood disorders, the condition most often associated with suicide.
      SSRIs were associated with a lower risk of suicide by antidepressant overdose
      compared with TCAs. CONCLUSION: The decline in the national suicide rate (1985
      1999) appears to be associated with greater use of non-tricyclic antidepressants.
      Treatment of a greater proportion of mood disorders with SSRIs and other second
      generation non-tricyclic antidepressants may further reduce the suicide rate.
      Controlled studies of the antisuicidal properties of antidepressants are needed
      in high-risk depressed patient populations.

PMID- 15554757
TI  - Topiramate in the long-term treatment of binge-eating disorder associated with
      obesity.
AB  - BACKGROUND: This study assessed the long-term effectiveness and tolerability of
      topiramate in binge-eating disorder (BED) with obesity. METHOD: Sixty-one
      patients with BED (DSM-IV-TR criteria) and obesity enrolled in a 14-week, single
      center, randomized, double-blind, placebo-controlled study. Completers (N = 35)
      were offered participation in a 42-week, open-label extension trial of
      topiramate. Fifteen patients who received topiramate and 16 patients who received
      placebo in the double-blind study entered the open-label trial. Topiramate was
      titrated from 25 mg/day to a maximum of 600 mg/day. The primary endpoint was
      change from baseline to final visit in weekly binge frequency using the last
      observation carried forward for all patients who received topiramate. Baseline
      for patients receiving double-blind topiramate was the beginning of the
      controlled study; for patients receiving placebo, baseline was the beginning of
      the open-label trial. Open-label data were gathered from December 1998 to
      November 2000. RESULTS: Forty-four patients (31 who received topiramate in the
      open-label trial plus 13 who received topiramate in the double-blind study only)
      received at least 1 dose of topiramate; 43 patients provided outcome measures at
      a median final dose of 250 mg/day. Mean weekly binge frequency declined
      significantly from baseline to final visit for all 43 patients (-3.2; p < .001),
      for the 15 patients who received topiramate during the controlled and open-label
      studies (-4.0; p < .001), and for the 15 patients who received topiramate only
      during the open-label trial (-2.5; p = .044). Patients also exhibited
      statistically significant reduction in body weight. The most common reasons for
      topiramate discontinuation were protocol nonadherence (N = 17) and adverse events
      (N = 14). CONCLUSION: Topiramate treatment was associated with enduring
      improvement in some patients with BED and obesity but was also associated with a
      high discontinuation rate.

PMID- 15554758
TI  - Adverse effects of St. John's Wort: a systematic review.
AB  - OBJECTIVE: To obtain an overview of the available clinical evidence on safety and
      tolerability of hypericum extracts, we reviewed (1) dropout rates and adverse
      effects in double-blind randomized trials comparing hypericum extracts and
      placebo or synthetic standard antidepressants; (2) dropout rates and adverse
      effects in large-scale observational studies; and (3) adverse effects reported in
      published cases and to public drug surveillance agencies. METHOD: Data on dropout
      rates and adverse effects were extracted from double-blind randomized trials of
      hypericum monopreparations collected for a Cochrane review (last search July
      2003) and from a PubMed search (text word hypericum; search dates 1998-January
      2003). Similar data were extracted from uncontrolled observational studies
      including at least 100 patients identified through a PubMed search (search term
      hypericum NOT animal, last update May 2003), contacts with manufacturers, and
      screening of review articles. Case reports and case series on adverse events
      associated with hypericum products were identified through a MEDLINE search (1966
      November 2002; search term: hypericum AND [adverse effects OR interaction]) and a
      PubMed search (February 2003) and were collected from 5 public drug surveillance
      agencies (data through May 2001). All database searches were conducted as English
      and non-English language searches. RESULTS: Data from 35 double-blind randomized
      trials showed that dropout and adverse effects rates in patients receiving
      hypericum extracts were similar to placebo, lower than with older
      antidepressants, and slightly lower than with selective serotonin reuptake
      inhibitors. Dropout rates due to adverse effects in 17 observational studies
      including 35,562 patients ranged from 0% to 5.7%; interactions or serious adverse
      effects were not reported in any study. Published cases and cases reported to
      drug surveillance agencies suggest that interactions with a variety of drugs
      (particularly cyclosporine in transplant patients) are the most relevant adverse
      effects of hypericum extracts. CONCLUSIONS: The available evidence suggests that
      hypericum extracts are well tolerated and safe if taken under control of a
      physician who is aware of potentially relevant risks in specific circumstances.

PMID- 15554759
TI  - An open trial of olanzapine in anorexia nervosa.
AB  - BACKGROUND: Recent reports raise the possibility that olanzapine can assist
      weight gain and improve behavioral symptoms during refeeding in anorexia nervosa.
      METHOD: Seventeen DSM-IV anorexia nervosa subjects hospitalized between May 1999
      and October 2000 were enrolled in open-label treatment with olanzapine for up to
      6 weeks. Baseline weight and symptoms were compared to patients' status at the
      end of treatment. RESULTS: Olanzapine administration was associated with a
      significant reduction in depression, anxiety, and core eating disorder symptoms,
      and a significant increase in weight. A comparison with our historical data
      suggests that subjects in this study had a significantly greater decrease in
      depression. CONCLUSION: These data lend support to the possibility that
      olanzapine may be useful in treating anorexia nervosa. However, a controlled
      trial is necessary to demonstrate that olanzapine is efficacious.

PMID- 15554760
TI  - Effect of lamotrigine on cognitive complaints in patients with bipolar I
      disorder.
AB  - BACKGROUND: This analysis describes the effects of bipolar I disorder on self
      reported neurocognitive measures and remediation of these deficits with
      lamotrigine therapy. METHOD: Data were derived from 2 clinical trials designed to
      assess the efficacy of lamotrigine as maintenance therapy for recently manic (N =
      349) or depressed (N = 966) patients (DSM-IV criteria). During the 8- to 16-week
      open stabilization phase, patients received lamotrigine as monotherapy or as
      adjunctive therapy (target dose = 200 mg/day, minimum dose = 100 mg/day) while
      other psychotropic drugs were discontinued. The Medical Outcomes Study Cognitive
      Scale (MOS-Cog) and the AB-Neurological Assessment Scale (AB-NAS) were used to
      measure cognitive functioning at baseline and at the end of the open-label phase.
      To examine the relationship between depressive and manic symptomatology,
      initiation of lamotrigine, and cognitive functioning, correlational analyses and
      analyses of covariance were conducted. RESULTS: Bipolar patients in both trials
      had significant cognitive impairment; however, it was much greater in index
      episode depressed bipolar patients compared with index episode manic patients. In
      both studies, substitution of lamotrigine for other psychotropic medications
      significantly improved the mean scores from baseline to the end of the open-label
      phase on the MOS-Cog and the AB-NAS (p < .0001). Among patients who took
      lamotrigine as monotherapy, the mean MOS-Cog score also improved significantly
      versus baseline (+32.2, or 81%, for depressed patients, p < .0001; and +19.9, or
      35%, for manic patients, p < .0001). Mean AB-NAS scores (-19.7, or -55%, for
      depressed patients, p < .0001; and -7.2, or -32%, for manic patients, p = .0062)
      showed similar improvement. Cognitive impairment was significantly correlated
      with depression symptom severity based on Hamilton Rating Scale for Depression
      scores (p < .0001). After controlling for change in mood, age, gender, baseline
      score, duration of illness, and duration of use of other psychotropics, a
      significant improvement in cognition was observed during the open-label phase
      when lamotrigine was used as monotherapy/adjunctive therapy. CONCLUSION:
      Treatment with lamotrigine as monotherapy and as adjunctive therapy was
      associated with improved cognitive functioning and reduced neurocognitive side
      effects, regardless of index mood polarity.

PMID- 15554761
TI  - Prevalence of hyperprolactinemia in schizophrenia: association with typical and
      atypical antipsychotic treatment.
AB  - OBJECTIVE: To evaluate the prevalence and severity of hyperprolactinemia among a
      large sample of patients with schizophrenia and related psychotic disorders
      treated with typical and atypical antipsychotic medications. METHOD: Three
      electronic databases (general medical, psychiatric, and pharmacologic) containing
      the census data from November 2002 through March 2003 for a state-funded,
      inpatient hospital serving the chronically mentally ill were merged (N = 470).
      This database was purged of patient names, while the unique hospital
      identification number and demographic variables in each record were retained.
      These records were then screened to exclude patients with medications (except
      neuroleptics) or medical conditions known to elevate or suppress prolactin,
      leaving an overall sample (N = 422) in which to evaluate the prevalence of
      hyperprolactinemia. The sample was composed of patients with DSM-IV schizophrenia
      (N = 213), other related psychotic disorders (N = 131), mood disorders (N = 44),
      and other disorders (N = 34). RESULTS: For the overall sample (N = 422), which
      combined men and women, the mean serum prolactin level was 41.5 ng/mL; 290 of 422
      patients were above the normal range. For women (N = 133), the mean serum
      prolactin level was 57.9 ng/mL, and 67% had levels above normal. For men (N =
      289), the mean level was 33.9 ng/mL, with a 70% prevalence of hyperprolactinemia.
      While age did not influence the prevalence of elevated prolactin among men, age
      (reflecting reproductive status) was a significant variable in women; older age
      was associated with lower prolactin levels. For the study sample, a highly
      significant correlation was observed between neuroleptic dose (chlorpromazine
      equivalent) and serum prolactin level; however, this relationship was not
      determined on a medication-by-medication basis. Medications known to elevate
      prolactin were associated with higher prevalence rates of hyperprolactinemia, and
      "prolactin-sparing" medications had lower prevalence rates. However, when they
      were used in combination, the prolactin-elevating medication overwhelmed the
      effects of prolactin-sparing medication. CONCLUSIONS: This study suggested that
      neuroleptic treatment of schizophrenia is strongly associated with
      hyperprolactinemia and showed important differences between prolactin-sparing and
      prolactin-elevating medications.

PMID- 15554762
TI  - Impact of depressive symptoms compared with manic symptoms in bipolar disorder:
      results of a U.S. community-based sample.
AB  - OBJECTIVE: In the present study, we assessed the functional impact of depressive
      versus manic symptoms in bipolar disorder. METHOD: A survey comprising the
      Sheehan Disability Scale (SDS), the Social Adjustment Scale Self-Report (SAS-SR),
      the Mood Disorder Questionnaire (MDQ), and other questions was mailed to a
      representative subset of 4810 individuals (with or without bipolar disorder) from
      a U.S. population-based epidemiologic study conducted in 2001. RESULTS: Of the
      3191 evaluable surveys returned, 593 respondents screened positive for bipolar
      disorder on the MDQ and/or reported a physician diagnosis of bipolar disorder. In
      the 4 weeks prior to the survey, subjects reported a mean of 12.4 days of
      depressive symptoms and 7.0 days of manic symptoms (p < .0001). The majority of
      days with depressive (79.8%) and manic (77.1%) symptoms were disruptive. Both
      total and mean scores on each domain of the SDS (work, social life, family life)
      reflect significantly greater impairment because of depressive versus manic
      symptoms during the 4 weeks prior to the survey (p < .0001). Among the 118
      employed subjects who missed at least 1 day of work in the past month, more
      workdays were missed because of depressive versus manic symptoms (0.78 vs. 0.15,
      p < .004). For each domain of the SAS-SR, functional impairment was attributed
      significantly more often to depressive symptoms than manic symptoms (p < .0001).
      Similar results were observed for the 12 months preceding the survey.
      CONCLUSIONS: Self-reported depressive symptoms are more frequent than manic
      symptoms and cause greater disruption of occupational, family, and social
      functioning. These findings underscore the need to improve the recognition and
      management of bipolar depression.

PMID- 15554763
TI  - Efficacy and tolerability of tranylcypromine versus phenelzine: a double-blind
      study in antidepressant-refractory depressed inpatients.
AB  - BACKGROUND: The aim of this study was to examine whether phenelzine is a suitable
      alternative to tranylcypromine in antidepressant-resistant depression. METHOD: A
      total of 77 severely depressed in-patients, meeting the DSM-IV criteria for major
      depressive disorder, who failed to respond to fixed plasma level treatment with
      either tricyclic antidepressants or fluvoxamine were withdrawn from psychotropic
      medication and included in a double-blind flexible-dose 5-week comparison of
      tranylcypromine and phenelzine. RESULTS: Of the 77 patients, 67 (87%) completed
      the trial, of whom 35 (52%) responded. No significant differences in response
      between both drugs were observed. Seventeen (44%) of 39 patients responded to
      tranylcypromine and 18 (47%) of 38 to phenelzine (> or = 50% reduction in
      Hamilton Rating Scale for Depression [HAM-D] score). The mean reduction in HAM-D
      score was 10.4 +/- 8.3 for the tranylcypromine sample versus 8.3 +/- 8.4 for the
      phenelzine-treated patients. Only a few patients (10%) used concomitant
      psychotropic medication. A substantial number of patients experienced severe side
      effects, mainly dizziness, agitation, and insomnia; the incidence was the same in
      both samples (21%). CONCLUSION: No difference in efficacy was observed between
      both monoamine oxidase inhibitors in a sample of patients with severe
      antidepressant-refractory depression. Phenelzine appears to be a suitable
      alternative to tranylcypromine.

PMID- 15554764
TI  - Multiplicity-adjusted sample size requirements: a strategy to maintain
      statistical power with Bonferroni adjustments.
AB  - BACKGROUND: A researcher must carefully balance the risk of 2 undesirable
      outcomes when designing a clinical trial: false-positive results (type I error)
      and false-negative results (type II error). In planning the study, careful
      attention is routinely paid to statistical power (i.e., the complement of type II
      error) and corresponding sample size requirements. However, Bonferroni-type alpha
      adjustments to protect against type I error for multiple tests are often
      resisted. Here, a simple strategy is described that adjusts alpha for multiple
      primary efficacy measures, yet maintains statistical power for each test. METHOD:
      To illustrate the approach, multiplicity-adjusted sample size requirements were
      estimated for effects of various magnitude with statistical power analyses for 2
      tailed comparisons of 2 groups using chi2 tests and t tests. These analyses
      estimated the required sample size for hypothetical clinical trial protocols in
      which the prespecified number of primary efficacy measures ranged from 1 to 5.
      Corresponding Bonferroni-adjusted alpha levels were used for these calculations.
      RESULTS: Relative to that required for 1 test, the sample size increased by about
      20% for 2 dependent variables and 30% for 3 dependent variables. CONCLUSION: The
      strategy described adjusts alpha for multiple primary efficacy measures and, in
      turn, modifies the sample size to maintain statistical power. Although the
      strategy is not novel, it is typically overlooked in psychopharmacology trials.
      The number of primary efficacy measures must be prespecified and carefully
      limited when a clinical trial protocol is prepared. If multiple tests are
      designated in the protocol, the alpha-level adjustment should be anticipated and
      incorporated in sample size calculations.

PMID- 15554765
TI  - Topiramate treatment of aggression in female borderline personality disorder
      patients: a double-blind, placebo-controlled study.
AB  - OBJECTIVE: The goal of this study was to compare the efficacy and safety of
      topiramate versus placebo in the treatment of aggression in women who meet the
      criteria for borderline personality disorder. METHOD: We conducted a double
      blind, placebo-controlled study of topiramate in 29 female subjects (response
      rate 93.5%) meeting SCID (Structured Clinical Interview for DSM-IV) criteria for
      borderline personality disorder. The subjects were randomly assigned in a 2:1
      ratio to topiramate (N = 21, analysis based on N = 19) or placebo (N = 10).
      Treatment lasted 8 weeks (November 2003-January 2004). Primary outcome measures
      were self-reported changes on the anger subscales of the State-Trait Anger
      Expression Inventory (STAXI). RESULTS: Significant improvements on 4 subscales of
      the STAXI (state-anger, trait-anger, anger-out, anger-control) were observed in
      the topiramate-treated subjects after 8 weeks, in comparison with the placebo
      group. The difference in improvement in score between the 2 groups for state
      anger, trait-anger, and anger-out ranged from 21% to 24%, and the difference for
      anger-control was -13%. As an exception, a difference of only 8.5% (p < .2) was
      found on the anger-in subscale. Significantly greater weight loss was observed in
      the topiramate-treated group than in those treated with placebo (difference in
      weight loss between the 2 groups: 2.3 kg [5.1 lb] [3.2%]; 95% CI = 1.3% to 4.4%,
      p < .01). All patients tolerated topiramate well. CONCLUSIONS: Topiramate appears
      to be a safe and effective agent in the treatment of anger in women with
      borderline personality disorder as defined by SCID criteria. Additionally,
      significant weight loss can be expected.

PMID- 15554766
TI  - Combining stimulants with monoamine oxidase inhibitors: a review of uses and one
      possible additional indication.
AB  - BACKGROUND: Among antidepressant augmentation strategies, the addition of a
      stimulant to a monoamine oxidase inhibitor (MAOI) has received little attention
      in the literature in recent years because of the diminished clinical use of the
      latter and concerns of precipitating a hypertensive crisis or other serious
      complication. Despite that fact, experienced clinicians continue to use this
      combination for a variety of indications after other options have failed. This
      article reviews these reported uses and presents a case suggesting another
      possible indication. METHOD: A MEDLINE search was conducted for articles
      published from 1962 to December 2003 using relevant search terms
      (psychostimulant, stimulant, amphetamine, dextroamphetamine, pemoline or
      methylphenidate, atomoxetine, bupropion, monoamine oxidase inhibitor, and
      selegiline). A manual search was conducted of cross-references and other relevant
      recent psychiatric sources (2000-2003). RESULTS: The described uses of the MAOI
      stimulant combination have included treatment of refractory depression and the
      MAOI-related side effects of orthostatic hypotension and daytime sedation. No
      documented reports were found in the recent literature of hypertensive crises or
      fatalities occurring when the stimulant was cautiously added to the MAOI. Also
      presented here is another possible indication for this therapeutic regimen:
      treatment of attention-deficit/hyperactivity disorder in an adult patient whose
      major depression had uniquely responded to the MAOI tranylcypromine. CONCLUSION:
      As in other fields of medicine, potentially hazardous medication combinations are
      utilized in psychiatry after cautiously weighing the danger of the treatment
      against the morbidity and risk of not adequately addressing the illness.
      Particularly, as the potential arrival of the apparently safer transdermal
      selegiline may increase the use of MAOIs, we feel this combination deserves
      additional controlled study.

PMID- 15554767
TI  - Effects of changing from typical to atypical antipsychotic drugs on subjective
      sleep quality in patients with schizophrenia in a Japanese population.
AB  - OBJECTIVE: To investigate the effects of the atypical antipsychotic drugs
      risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of
      sleep in patients with schizophrenia. METHOD: Subjects were 92 inpatients (mean
      age = 59.9 years) who had been receiving treatment with conventional
      antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects
      were randomly assigned to receive 1 of 4 atypical antipsychotic drugs
      (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality
      and psychopathology were assessed twice: at baseline and 8 weeks after switching.
      Data were collected from June 2001 to December 2001. Subjective sleep quality was
      assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was
      measured by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Subjective
      sleep quality as assessed by the PSQI was significantly improved with
      administration of olanzapine, risperidone, or quetiapine, but not with
      perospirone, in comparison with conventional antipsychotic drugs. Multiple
      regression analysis revealed that the improvement of sleep quality with
      administration of atypical antipsychotic drugs was predicted by poor sleep
      quality at baseline. In addition, improvement of sleep quality was significantly
      correlated with improvement of negative symptoms as assessed by the PANSS.
      CONCLUSION: These results demonstrated that atypical antipsychotic drugs improved
      subjective quality of sleep in patients with schizophrenia compared with
      conventional antipsychotic drugs, suggesting that the marked potency of serotonin
      2 receptor blockade in atypical antipsychotic drugs may be involved in the
      mechanism of this improvement. These improvements were correlated with
      improvement of negative symptoms.

PMID- 15554768
TI  - A retrospective analysis of quetiapine in the treatment of pervasive
      developmental disorders.
AB  - BACKGROUND: The purpose of this study was to examine the effectiveness and
      tolerability of quetiapine for aggression, hyperactivity, and self-injury in
      pervasive developmental disorders (PDDs). METHOD: The medical records of all
      patients with PDDs diagnosed according to DSM-IV criteria and treated with
      quetiapine were retrospectively reviewed. Patients who received quetiapine for at
      least 4 weeks and who were not concurrently treated with another antipsychotic or
      mood stabilizer were included. Improvement was measured with the Clinical Global
      Impressions-Improvement scale (CGI-I), with response determined by ratings of
      "much improved" or "very much improved." Data were collected from May 15, 2003
      through November 30, 2003. RESULTS: Of 857 records reviewed, 20 patients (16
      male, 4 female) (mean +/- SD age = 12.1 +/- 6.7 years; range, 5-28 years)
      received a quetiapine trial (mean +/- SD dosage = 248.7 +/- 198.4 mg/day; range,
      25-600 mg/day) over a mean duration of 59.8 +/- 55.1 weeks (range, 4-180 weeks).
      Eight (40%) of 20 patients were judged "responders" to quetiapine; the mean CGI-I
      score for the entire group was 3.0 +/- 1.1 (minimally improved). A statistically
      significant improvement (p = .002) was found between a mean pretrial CGI-Severity
      of Illness scale (CGI-S) score of 5.1 +/- 0.6 (markedly ill) and a posttrial CGI
      S score of 4.2 +/- 1.1 (moderately ill). Adverse effects occurred in 50% (N = 10)
      of patients and led to drug discontinuation in 15% (N = 3) of patients.
      CONCLUSION: Quetiapine was modestly effective for maladaptive behavior in
      patients with a PDD. Controlled studies are needed to further assess these
      preliminary findings.

PMID- 15554769
TI  - Possible induction of mania or hypomania by atypical antipsychotics: an updated
      review of reported cases.
AB  - BACKGROUND: Atypical antipsychotics are widely used in clinical practice for
      several psychiatric disorders. Between 1994 and 1999, 26 cases of manic and
      hypomanic syndromes were reported with olanzapine and risperidone and were
      described in a previous review article. METHOD: An updated MEDLINE search (1999
      2003) using the terms atypical antipsychotics, amisulpride, aripiprazole,
      clozapine, flupenthixol, olanzapine, quetiapine, risperidone, sertindole,
      ziprasidone, zotepine, hypomania, and mania showed that 34 new cases of induced
      hypomanic or manic syndromes have been published, not only with olanzapine (N =
      5) and risperidone (N = 6), but also with quetiapine (N = 5) and ziprasidone (N =
      11) treatment. Six cases have been reported with flupenthixol and 1 with
      amisulpride, two antipsychotics considered as "partial" atypicals. RESULTS: A
      critical analysis of these case reports revealed that the effects on mood were
      insufficiently documented in some of the reports but that for 20 of them,
      evidence is highly suggestive of a causative role of atypical antipsychotics in
      the induction of manic/hypomanic symptomatology. CONCLUSION: This updated review
      continues and extends the results of the initial review and suggests that
      atypical antipsychotics have some intriguing effects on mood. Such effects have
      never been reported with conventional antipsychotics. The mechanisms involved in
      this phenomenon of mood switch remain to be elucidated.

PMID- 15554770
TI  - Body mass index and future schizophrenia in Israeli male adolescents.
AB  - BACKGROUND: Compared with the general population, individuals suffering from
      schizophrenia are more likely to be overweight, a finding attributed to the
      effect of antipsychotic medications, poor nutrition, and sedentary lifestyle. As
      evidence accumulates indicating that some aspects of the illness manifest before
      the onset of psychosis and establishment of the diagnosis, it has been suggested
      that increased weight, like other metabolic dysfunctions, might precede active
      illness. METHOD: Data on height and weight of 203,257 male adolescents assessed
      by the Israeli Draft Board, and followed for 2-6 years for later hospitalization
      for schizophrenia using the Israeli National Psychiatric Hospitalization Case
      Registry, were analyzed. RESULTS: From the entire cohort, 309 (0.15%) were later
      hospitalized for schizophrenia (ICD-10). After removing adolescents with evidence
      of illness before or within 1 year of the Draft Board assessment, 204 future
      schizophrenia patients were available for analysis. Compared with the rest of the
      cohort, future schizophrenia patients had lower body mass indexes (21.24 +/- 3.3
      kg/m2 vs. 21.77 +/- 3.5 kg/m2; F = 4.682, df = 1, p = .03) and weighed slightly
      but significantly less (64.2 +/- 11.6 kg vs. 66.3 +/- 12.0 kg; F = 6.615, df = 1,
      p = .01). The mean height of the future patients did not differ significantly
      from the mean height of the remaining cohort (173.63 +/- 6.7 cm vs. 174.40 +/-
      6.9 cm; F = 2.520, df = 1, p = .112). When reanalyzing the data, controlling for
      physical activity and socioeconomic status, the differences between the groups
      remained significant. CONCLUSION: Before the onset of illness, future
      schizophrenia patients are not heavier compared with their peers. This implies
      that the increased weight of patients with schizophrenia is related to illness
      effects, including the effects of antipsychotic medication.

PMID- 15554771
TI  - Vitamin B6 treatment in acute neuroleptic-induced akathisia: a randomized, double
      blind, placebo-controlled study.
AB  - BACKGROUND: Treatment strategies for acute neuroleptic-induced akathisia (NIA)
      contain anticholinergic (antimuscarinic) agents, dopamine agonists, gamma
      aminobutyric acid (GABA)-ergic agents, beta-blockers, benzodiazepines, and
      serotonin antagonists. Nevertheless, many patients who suffer from acute
      akathisia fail to respond to treatment. In earlier studies, vitamin B6 was found
      to be effective in the treatment of neuroleptic-induced movement disorders. The
      purpose of this study was to evaluate the efficacy of vitamin B6 in the treatment
      of acute NIA. This is the first report of B6 as a treatment for NIA. METHOD: This
      study was conducted in 2 mental health centers from February 2003 to November
      2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis
      of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or
      placebo (N = 10) twice a day for 5 days in a double-blind design. The Barnes
      Akathisia Scale (BAS), the Brief Psychiatric Rating Scale (BPRS), and the
      Clinical Global Impressions scale (CGI) were used to assess the severity of NIA
      and psychotic symptoms. The BAS assessment was made at baseline and every day
      during the study. The BPRS and CGI were completed at baseline and at the end of
      the study. RESULTS: The vitamin B6-treated patients in comparison with the
      placebo group showed a significant improvement on the subjective-awareness of
      restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004)
      subscales of the BAS. The objective subscale did not demonstrate significant
      positive results (p = .079), but there was a trend of symptom amelioration in the
      vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was
      noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the
      placebo group (30%) (p = .037). CONCLUSION: Our preliminary results indicate that
      high doses of vitamin B6 may be useful additions to the available treatments for
      NIA, perhaps due to its combined effects on various neurotransmitter systems.

PMID- 15554772
TI  - Body-image dissatisfaction in gay versus heterosexual men: is there really a
      difference?
AB  - BACKGROUND: Gay men are thought to experience body-image concerns or disorders
      more frequently than heterosexual men. It is unclear, however, whether these
      putative concerns are due to unrealistic body ideals (aspiring to a body shape
      that is difficult or impossible to attain), body-image distortion (misperceiving
      the actual shape of one's body), or both. METHOD: We administered a well
      established computerized body-image test, the "somatomorphic matrix," to 37 gay
      men recruited from the community in April 1999 and compared the results with
      previous data from 49 community-recruited heterosexual comparison men and 24
      clinic-recruited heterosexual men with eating disorders. RESULTS: Gay men were
      indistinguishable from the community-recruited heterosexual comparison men on
      measures of both body ideals and body-image distortion. By contrast, eating
      disordered men were significantly distinguishable from both other groups on body
      image distortion. The lack of differences between community gay and heterosexual
      men on body-image indices seems unlikely to represent a type II error, since the
      somatomorphic matrix showed ample power to detect abnormalities in the eating
      disordered men, despite the smaller sample size of the latter group. CONCLUSION:
      Contrary to our hypotheses, gay men did not differ significantly from
      heterosexual men on measures of body image. These unexpected findings cast doubt
      on the widespread belief that gay men experience greater body-image
      dissatisfaction than heterosexual men. If our findings are valid, it follows that
      some previous studies of body image in gay men may possibly have been influenced
      by selection bias.

PMID- 15554773
TI  - Treatment of posttraumatic stress disorder with phenytoin: an open-label pilot
      study.
AB  - BACKGROUND: Phenytoin is an anticonvulsant used in the treatment of epilepsy. Its
      mechanism of action is incompletely understood but most likely involves
      modulation of glutamatergic transmission. The neurobiology of posttraumatic
      stress disorder (PTSD) has been hypothesized to involve, at least in part,
      alterations in glutamatergic transmission in the hippocampus and possibly other
      brain regions. The purpose of this study was to assess the effects of phenytoin
      on symptoms of PTSD. METHOD: Phenytoin was administered in an open-label fashion
      for 3 months to 9 adult male and female patients with DSM-IV PTSD related to a
      variety of traumas including childhood abuse, combat, and car accidents. Dosage
      was adjusted to maintain the therapeutic blood levels used in the treatment of
      epilepsy. Subjects were assessed before, during, and after treatment for PTSD
      with standardized dimensional measures of disease severity including the
      Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for
      Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Data were
      collected from November 2001 through June 2003. RESULTS: Phenytoin treatment
      resulted in a significant decrease in PTSD symptoms as measured with the CAPS
      (mean score = 65 pretreatment vs. 38 posttreatment) with reductions in each of
      the symptom clusters of intrusions, avoidance, and hyperarousal (p < .05). There
      were no significant decreases in symptoms of depression severity as measured with
      the HAM-D or anxiety severity as measured with the HAM-A. CONCLUSIONS: These
      findings suggest that phenytoin may be efficacious in the treatment of PTSD,
      possibly mediated through its antiglutamatergic effects. Randomized, controlled,
      double-blind clinical trials are indicated to further evaluate this medication in
      the treatment of PTSD.

PMID- 15554774
TI  - Utilizing benzodiazepines in clinical practice: an evidence-based discussion.

PMID- 15554775
TI  - Can bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS)
      induce mania? A case report.

PMID- 15554776
TI  - A case of venous thromboembolism probably associated with hyperprolactinemia
      after the addition of olanzapine to typical antipsychotics.

PMID- 15554778
TI  - Prescribing benzodiazepines for patients with substance use disorders.

PMID- 15554779
TI  - Anger in depressive mixed states.

PMID- 15554781
TI  - Beyond refractory obsessions and anxiety states: toward remission.
AB  - At the Sixth International Obsessive-Compulsive Disorder Conference (IOCDC), held
      November 13-15, 2003, in Lanzarote, Spain, 2 issues were discussed that are of
      great importance to future research on obsessive-compulsive disorder (OCD). The
      first of these is the possible inclusion of obsessive-compulsive spectrum
      disorders (OCSD) in the fifth edition of the Diagnostic and Statistical Manual of
      Mental Disorders. OCSD resemble OCD in their clinical symptoms, associated
      features, comorbidity, family/genetics, etiology, and neurocircuitry, as well as
      their selective response to treatment with serotonin reuptake inhibitors. The
      second issue is considering remission as the ultimate goal of treatment for OCD
      instead of just symptom reduction, as has been suggested in other disorders.
      These and other issues should be discussed at future meetings of the IOCDC and
      influence how we conceptualize the disorder and design future treatment trials.

PMID- 15554782
TI  - A qualitative analysis of nonresponse: management of treatment-refractory
      obsessive-compulsive disorder.
AB  - Serotonin reuptake inhibitors (SRIs), especially potent ones given at high doses
      over long periods of time, are often effective in the treatment of obsessive
      compulsive disorder (OCD). However, a large percentage of patients do not respond
      to treatment with SRIs, and those who do respond often do not fully remit, which
      should be the standard goal of treatment in OCD. If a patient has been treated
      for several months and has not yet responded to treatment with several SRIs, the
      physician should perform a careful assessment of resistant and/or residual
      clinical symptoms and any comorbid conditions to determine which next-step
      treatment would be the most appropriate. One strategy for patients who have not
      responded to treatment with an SRI is to switch them to a serotonin
      norepinephrine reuptake inhibitor, because some patients may respond better to
      agents that target multiple systems. Another promising approach is the
      augmentation of SRIs with neuroleptics. In addition, open trials have shown that
      intravenous (IV) clomipramine and IV citalopram may be effective in the treatment
      of resistant OCD. Novel pharmacotherapeutic treatments and electroconvulsive
      therapy have been attempted, with mixed success. Recently, researchers have been
      studying repetitive transcranial magnetic stimulation, vagal nerve stimulation,
      and neurosurgical approaches such as gamma knife capsulotomy and deep brain
      stimulation to learn if these procedures are effective in treating treatment
      resistant OCD. Repetitive transcranial magnetic stimulation has possibilities not
      only as a therapy but also as an instrument that can help researchers describe
      the neurocircuitries involved in OCD. More results are needed before the
      effectiveness of the nonpharmacologic treatments for OCD can be determined.

PMID- 15554783
TI  - The role of dopamine in obsessive-compulsive disorder: preclinical and clinical
      evidence.
AB  - Obsessive-compulsive disorder (OCD) is a frequent and chronic psychiatric
      disorder that has been linked closely to the serotonin system mainly because of
      the antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs).
      A limitation of the serotonin hypothesis of OCD is that a substantial number of
      the patients with OCD show no significant improvement after an adequate trial
      with SSRIs. There is substantial evidence that these patients may benefit from
      addition of antipsychotics to their ongoing SSRI treatment, suggesting that
      dopamine also might play a role in the pathophysiology of OCD. In this review,
      the preclinical and clinical evidence on the role of dopamine in OCD is
      summarized.

PMID- 15554784
TI  - Serotonin-1D hypothesis of obsessive-compulsive disorder: an update.
AB  - Support for the serotonin-1D (5-HT(1D)) hypothesis of obsessive-compulsive
      disorder (OCD) and related conditions comes from a variety of sources. Some
      pharmacologic challenges with the 5-HT(1D) agonist sumatriptan, and case reports
      in which prolonged administration of 5-HT(1D) agonists was associated with a
      therapeutic effect, suggest that 5-HT(1D) may play a role in obsessive-compulsive
      symptoms. Genetic studies have also found that polymorphism of the 5-HT(1D) gene
      may be preferentially transmitted to those patients with OCD. However, taking
      into account that OCD is a heterogeneous syndrome, the 5-HT(1D) hypothesis
      requires further investigation in order to disentangle the role of the 5-HT(1D)
      receptor in this common and often severe disorder.

PMID- 15554785
TI  - Overview of panic and social anxiety disorders.
AB  - Panic disorder and social anxiety disorder are often-overlooked but debilitating
      disorders that share some common symptoms and treatments. Patients with panic
      disorder experience unexpected panic attacks and then worry about having more
      attacks. Those with social anxiety disorder fear doing or saying something
      embarrassing in social situations. The prevalence of these conditions is about 3%
      for panic disorder and 13% for social anxiety disorder in the United States and
      is higher in women than in men. Both disorders are thought to have a familial
      link and to be related to dysregulation of neurotransmitter systems. Panic and
      social anxiety disorders are often comorbid with other psychiatric disorders.
      Medication treatment and/or cognitive-behavioral therapy might need to be
      continued over the long term to prevent relapse.

PMID- 15554786
TI  - The social anxiety disorder spectrum.
AB  - BACKGROUND: Current diagnostic classifications emphasize the categorical nature
      of disorders such as social anxiety disorder. Nevertheless, phenomenological and
      psychobiological data have led to the hypothesis that social anxiety symptoms and
      disorders lie on various dimensions. METHOD: A MEDLINE search (1966-2003) for
      relevant articles on the social anxiety disorder spectrum was undertaken using
      the terms shyness, behavioral inhibition, social phobia, social anxiety disorder,
      avoidant personality, dimension, and spectrum to aim at objective coverage, but
      references for this article were chosen more subjectively to illustrate data and
      themes in description, pathogenesis, pharmacotherapy, and psychotherapy of the
      social anxiety disorder spectrum. RESULTS: Several different approaches to
      delineating a social anxiety disorder spectrum of conditions have been described.
      These include (1) a spectrum of social fear and avoidance, (2) a spectrum of body
      focused concerns, (3) a spectrum of anxiety disorders and affective dysfunction,
      and (4) a spectrum of social deficits. CONCLUSIONS: Social anxiety symptoms and
      disorders do appear to lie on a number of different dimensions. Nevertheless,
      additional research is necessary to determine the clinical utility of assessing
      these different dimensions and to investigate their underlying psychobiology.

PMID- 15554788
TI  - Call to clinical action.

PMID- 15554789
TI  - Recognition and diagnosis of bipolar disorder.
AB  - Bipolar disorder is a serious, recurrent, and sometimes chronic psychiatric
      illness that is far more prevalent than many physicians realize. It often is
      unrecognized and misdiagnosed, particularly in patients presenting with
      depression. The consequences of misdiagnosis and mistreatment as unipolar
      depression may be disastrous. The rate of recognition may be improved by asking
      patients about bipolar symptoms and by screening for bipolar disorder using the
      Mood Disorder Questionnaire.

PMID- 15554790
TI  - Improving the course of illness and promoting continuation of treatment of
      bipolar disorder.
AB  - The course and characteristics of the different types of bipolar disorder have
      profound implications for its long-term prognosis and treatment. Patients with
      bipolar I disorder are symptomatically ill nearly half the time and have a high
      probability of relapse. Bipolar II disorder is more chronic, more depressive, and
      associated with more neuroticism and emotional instability between episodes than
      bipolar I. Impaired psychosocial functioning and a high risk for suicide are
      common to all types of bipolar disorder. The illness can be stabilized through
      pharmacotherapy and by patients maintaining orderly patterns of life activities
      and using psychotherapy, psychoeducation, and mood charting. Adherence to
      pharmacotherapy increases the duration of remission. Physicians can help improve
      adherence by selecting medications with simple dosage regimens and educating
      patients and families about the disorder and what to expect from medications.

PMID- 15554791
TI  - Employing pharmacologic treatment of bipolar disorder to greatest effect.
AB  - Mechanisms of action, onset and duration of action, and interactions with other
      medications--all of these pharmacokinetic properties of pharmacologic agents
      affect the efficacy and safety of therapeutic regimens for bipolar disorder. For
      example, antiglutamatergic agents such as lamotrigine may relieve depression but
      have no impact on mania. Atypical antipsychotics with the dual effect of blocking
      dopamine and serotonin receptors in the brain decrease psychosis, mania, and,
      according to some preliminary indications, possibly depression. The impact of
      these properties has been borne out in clinical studies. Mood stabilizers such as
      lithium and valproate stabilize mood by significantly decreasing the manic and
      hypomanic symptoms of bipolar disorder, although they can have effects on
      depressive symptoms too. Lamotrigine stabilizes mood by reducing depression. The
      atypical anti-psychotics have been shown to be effective either as monotherapy or
      in combination with mood stabilizers.

PMID- 15554792
TI  - Making optimal use of combination pharmacotherapy in bipolar disorder.
AB  - Because patients with bipolar disorder often do not respond sufficiently to
      treatment with 1 mood stabilizer, psychiatrists frequently employ combination
      therapy and add antipsychotics, antiepileptics, or antidepressants to mood
      stabilizers. Combination therapy can be more effective than monotherapy in
      controlling breakthrough or treatment-resistant episodes. For example, atypical
      antipsychotics have been shown to be effective adjunctive treatments for mania
      and for patients with psychotic symptoms during a depressive episode, while the
      combination of a mood stabilizer and lamotrigine or an anti-depressant has been
      found to control bipolar depression. The American Psychiatric Association
      guideline for the treatment of bipolar disorder recommends optimizing individual
      medications before switching to combination therapy. Selecting a combination
      treatment regimen with an acceptable side effect profile is critically important
      because patients may discontinue therapy they cannot tolerate. Agents should be
      added carefully, with continued monitoring of adverse effects. Physicians should
      give patients only as much medication as needed.

PMID- 15554793
TI  - Defining and improving response to treatment in patients with bipolar disorder.
AB  - Functional outcomes are more meaningful measures of response to treatment for
      bipolar disorder than are scores on various psychiatric rating scales (all of
      which have limitations) used to gauge improvement in symptoms. With the former
      approach, patients are considered to be in remission if they achieve normal or
      near-normal levels of functioning in occupational, family, and social settings.
      Sleep patterns are reliable indicators of whether a patient with bipolar disorder
      is likely to relapse or sustain remission in the near term. Regularly scheduled
      nightly sleep periods may help prevent rapid cycling in patients with mania,
      while perturbations in circadian rhythms may be early markers of impending
      relapse. Medications used to attain response and/or remission in maintenance
      therapy include lithium and valproate. The choice of mood stabilizer depends on
      the patient's symptoms, prior response to a mood stabilizer, and tolerance of the
      drug. For patients requiring additional therapy, combination regimens with mood
      stabilizers and atypical antipsychotics appear effective. Psychoeducation for
      patients and families and interpersonal psychotherapy also can help prolong
      remission.

PMID- 15554794
TI  - Diagnosis and treatment of bipolar disorder in children and adolescents.
AB  - Bipolar disorder is a serious illness in children that adversely affects social,
      academic, emotional, and family functioning. Its prevalence in adolescents is
      estimated to be as high as 1%. The diagnosis of bipolar disorder in young
      children is often a challenge, largely because the symptoms may differ from those
      exhibited in late adolescence and adulthood. The occurrence of comorbid disorders
      such as attention-deficit/hyperactivity disorder also may complicate the
      diagnosis. Despite the significant severity and chronicity of this disorder in
      youths, very few controlled data are available to guide treatment decisions in
      children and adolescents. The treatment literature consists largely of open
      studies, case series, and case reports. Therefore, a pressing need exists for
      controlled trials to determine whether medications commonly used to treat the
      disorder in children are significantly superior to placebo, as well as to
      determine whether initial monotherapy or combination treatment is warranted. This
      article will review the epidemiology, diagnosis, course of illness, and treatment
      of bipolar disorder in children and adolescents.

PMID- 15554795
TI  - Diagnosing and treating comorbid (complicated) bipolar disorder.
AB  - Comorbidity is the rule, not the exception, in bipolar disorder. The most common
      mental disorders that co-occur with bipolar disorder in community studies include
      anxiety, substance use, and conduct disorders. Disorders of eating, sexual
      behavior, attention-deficit/hyperactivity, and impulse control, as well as autism
      spectrum disorders and Tourette's disorder, co-occur with bipolar disorder in
      clinical samples. The most common general medical comorbidities are migraine,
      thyroid illness, obesity, type II diabetes, and cardiovascular disease.
      Bipolarity is a marker for comorbidity, and comorbid disorders, especially
      multiple conditions occurring when a patient is young, may be a marker for
      bipolarity. Relatively few controlled clinical studies have examined the
      treatment of bipolar disorder in the context of comorbid conditions (i.e.,
      complicated or comorbid bipolar disorder). However, the first step in treating
      any type of complicated bipolar disorder--stabilizing a patient's mood--may be
      associated with improving the comorbid disorder. Standard mood stabilizers,
      atypical antipsychotics, and non-antimanic antiepileptic agents are emerging as
      potentially useful treatments for several of the disorders that frequently co
      occur with bipolar disorder, and therefore may be useful treatments for comorbid
      bipolar disorder.

PMID- 15554796
TI  - Multicultural competency in research: examining the relationships among
      multicultural competencies, research training and self-efficacy, and the
      multicultural environment.
AB  - Research on multicultural competencies has mainly focused on the practice
      dimension of psychology training and practice. Little theoretical or empirical
      research has examined multicultural research training and self-efficacy. In this
      study, 119 psychology graduate students filled out a Web survey focusing on the
      research training environment, research self-efficacy, multicultural competency,
      the multicultural environment, and social desirability. Results showed that
      multicultural competency, research training, and the multicultural environment
      were related to multicultural research self-efficacy. Hierarchical regressions
      showed that multicultural competency predicted students' research anxiety; social
      desirability predicted multicultural research utility, multicultural competency,
      and the research training environment; and multicultural competency predicted
      students' confidence in research and perceptions that their graduate training
      programs were multicultural. Implications are discussed.

PMID- 15554797
TI  - Individuation among bedouin versus urban arab adolescents: ethnic and gender
      differences.
AB  - Three scales assessing individuation (Objective Measure of Ego-Identity Status
      [OMEIS], Separation-Individuation Test of Adolescence [SITA], and
      Multigenerational Interconnectedness Scale [MIS]) were administered to 40 female
      and 38 male Bedouin Arab adolescents and to 39 female and 38 male urban Arab
      adolescents in Grade 12. It was hypothesized that Bedouin Arab adolescents and
      female adolescents would manifest less individuation than urban Arab adolescents
      and male adolescents, respectively. Results from the OMEIS revealed that the
      identity foreclosed mean of the Bedouin adolescents was higher than that of the
      urban adolescents. As for the SITA, significant differences were found between
      Bedouin and urban Arabs in terms of dependency denial, separation anxiety,
      teacher enmeshment, peer enmeshment, and rejection expectancy. Significant gender
      differences were found in regard to dependency denial, and a borderline
      difference was found for separation anxiety. Significant effects of ethnicity and
      gender were found on the financial interconnectedness subscale of the MIS. The
      results support the present hypotheses concerning ethnicity differences and
      indicate that urbanization seems to narrow the differences in individuation
      between male and female adolescents.

PMID- 15554798
TI  - Inventory of college challenges for ethnic minority students: psychometric
      properties of a new instrument in Chinese Americans.
AB  - The Inventory of College Challenges for Ethnic Minority Students (ICCEMS) is a
      newly developed instrument that assesses challenges faced by ethnic minority
      college students across a range of cultural, academic, social, and practical
      domains. The present study tested the ICCEMS among Chinese American students in
      an attempt to identify its factor structure and assess its psychometric
      properties. A total of 13 factor domains emerged. The Cronbach's alpha and 1
      month test-retest reliability of the subscales and the overall scale supported
      their reliability. Both criterion and construct validities were also
      demonstrated. Chinese American college students faced the greatest challenges in
      terms of unclear career direction and academic demands.

PMID- 15554799
TI  - Cultural identity, explanatory style, and depression in Navajo adolescents.
AB  - This study investigated the interrelationships among cultural identity,
      explanatory style, and depression in Navajo adolescents. A total of 332 (197
      female, 135 male) Navajo adolescents completed 7 self-report measures. These data
      were used to create, via structural equation modeling, a series of factor models
      and full structural models. Analyses indicated that current factor structures for
      explanatory style and depression are adequate for use with Navajo adolescents.
      Increased control and predictability and limited duration of stressful encounters
      were both predictive of decreased symptoms of depression. Higher levels of Navajo
      cultural identity had a modest effect in terms of reducing depression. Other
      factors, such as perceived discrimination and urban/reservation domicile, are
      important to study to provide an increased understanding of depression among
      Navajo adolescents.

PMID- 15554800
TI  - Ethnic differences in battered women's formal help-seeking strategies: a focus on
      health, mental health, and spirituality.
AB  - The primary goal of this study was to identify ethnic differences in battered
      women's use of health, mental health, and spiritual coping strategies, as well as
      differences in the perceived helpfulness of each strategy. The authors recruited
      a sample of 376 African American and Caucasian victims of interpersonal violence
      from various sites. In comparison with Caucasian women in the sample, African
      American women were significantly more likely to report using prayer as a coping
      strategy and significantly less likely to seek help from mental health
      counselors. The 2 groups did not significantly differ in terms of the extent to
      which they sought help from clergy or medical professionals. African American
      women found prayer to be more helpful than did Caucasian women.

PMID- 15554801
TI  - A daily diary study of mental health and community involvement outcomes for three
      Chinese American social identities.
AB  - Approximately 100 American youths of Chinese descent participated in a 14-day
      diary study, completing daily reports on ethnic feelings, American feelings,
      ethnic community involvement, and psychological well-being. Participants were
      divided into 4 identity orientations (Chinese, American, bicultural, or other)
      and then assessed for differential patterns of mental health and community
      involvement. Chinese-centered identities were characterized by positive well
      being and positive self-esteem. However, the American-centered and bicultural
      groups had well-being and self-esteem levels equal to that of the Chinese
      centered group. Although the measures of menial health failed to differentiate
      the identity categories, both the Chinese- and bicultural-centered groups showed
      high involvement in Chinese culture, whereas American-centered participants were,
      significantly less involved.

PMID- 15554803
TI  - Exposure to violence and low-income children's mental health: direct, moderated,
      and mediated relations.
AB  - The authors examined the association between exposure to violence and different
      indexes of mental health among 95 extremely poor children (age range = 8-17
      years) and analyzed potential moderators and mediators. Findings indicated that
      62% of youths had been exposed to at least 1 form of violence. Controlling for
      other explanatory factors, exposure to violence was significantly associated with
      internalizing symptoms (e.g., depression, anxiety) across all children, but the
      relation was stronger for girls compared with boys. Externalizing problem
      behaviors were also associated with exposure to violence, but subgroup
      differences were not detected. Regression analyses indicated that self-esteem and
      a measure of perceived chronic danger may partially mediate the link between
      violence exposure and mental health symptoms.

PMID- 15554804
TI  - Measuring child maltreatment: a comparison of prospective parent reports and
      retrospective adolescent reports.
AB  - Using Lehigh Longitudinal Study data (N = 457), the authors compare prospective
      parent self-reports and retrospective adolescent reports of early childhood
      physical abuse, exploring their correspondence, predictive equivalence, and
      outcomes associated with conflicting reports. Correspondence between prospective
      and retrospective reports of child maltreatment was moderate (Phi = 0.27).
      Concurrence rates were similar for males and females. Analyses of the relative
      predictive capacity of prospective and retrospective measures revealed both to be
      significant predictors of key outcomes in adolescence. Findings support the
      predictive validity of both measures of childhood maltreatment and underscore the
      methodological challenges of measuring this important construct. Given the
      abundance and salience of research on the consequences of childhood maltreatment,
      greater attention to such measurement issues is due.

PMID- 15554805
TI  - Subgroups of physically abusive parents based on cluster analysis of parenting
      behavior and affect.
AB  - Cluster analysis of observed parenting and self-reported discipline was used to
      categorize 83 abusive parents into subgroups. A 2-cluster solution received
      support for validity. Cluster 1 parents were relatively warm, positive,
      sensitive, and engaged during interactions with their children, whereas Cluster 2
      parents were relatively negative, disengaged or intrusive, and insensitive.
      Further, clusters differed in emotional health, parenting stress, perceptions of
      children, and problem solving. Children of parents in the 2 clusters differed on
      several indexes of social adjustment. Cluster 1 parents were similar to
      nonabusive parents (n = 66) on parenting and related constructs, but Cluster 2
      parents differed from nonabusive parents on all clustering variables and many
      validation variables. Results highlight clinically relevant diversity in
      parenting practices and functioning among abusive parents.

PMID- 15554806
TI  - A family of trust: African American parents' stories of adoption disclosure.
AB  - Dramatic increases in same-race adoptions of African American children have
      stimulated interest in the experiences of these families, including those related
      to disclosure. Data from interviews with 27 African American adoptive parents (7
      mothers and fathers interviewed conjointly, 13 mothers interviewed alone) from 20
      different families revealed the following themes: (a) efforts to prevent trauma
      to the child; (b) respect for the child's differentness and birth history; (c)
      developmental decisions in disclosure; (d) children's questions as motivations
      for disclosure; and (e) parents' feelings about disclosure. Findings confirm the
      importance of psychoeducation regarding methods and timing of disclosure and
      provide support for comparative research on contemporary disclosure, including
      racial differences in process and content.

PMID- 15554807
TI  - When Asian immigrant women speak: from mental health to strategies of being.
AB  - Immigrant women from 5 ethnic-cultural communities (Korean, Hong Kong Chinese,
      Mainland Chinese, Taiwanese, and Vietnamese) in Toronto, Ontario, Canada
      participated in a focus group study (13 focus groups of 102 participants) of
      Asian immigrant women's conceptions of mental health. Their responses challenge
      the predominant conceptualizations of mental health in North America, the popular
      characterization of Asian culture as collectivistic, and the stereotypic image of
      Asian women as defining themselves in family relations. In trying to live a life
      they desire and to quest for a better state of well-being, these women have
      asserted their agency to articulate multiple strategies of being.

PMID- 15554808
TI  - Children's play narratives: what they tell us about lesbian-mother families.
AB  - Play narratives can offer a unique insight into the child's internal world. This
      study compared the play narratives of children in 38 lesbian-mother families; 73
      two-parent, heterosexual-mother families; and 58 single-heterosexual-mother
      families recruited from a general population sample. Findings indicated positive
      mother-child relationships and well-adjusted children. Girls' narratives showed
      more affection than boys' and were more strongly associated with mothers'
      interview measures, suggesting that girls' play narratives reveal a more accurate
      picture of family relationships.

PMID- 15554809
TI  - The person in recovery from acute and severe psychosis: the role of dependency,
      self-criticism, and efficacy.
AB  - The role of 3 personality dimensions (i.e., dependency, self-criticism, and
      efficacy) in recovery from an acute and severe psychosis was examined.
      Conceptualizing psychosis as involving difficulties in establishing psychological
      boundaries, the authors hypothesized that dependency has a greater disruptive
      effect on recovery than self-criticism. Results of a reanalysis of longitudinal
      data (N = 76) of people with schizophrenia spectrum disorders during recovery
      from acute psychosis were consistent with this hypothesis: Dependency predicted
      depressive and negative symptoms, and, under low efficacy, perceived loss of
      independence and insight into the presence of the illness. These findings
      elucidate the central role of interpersonal relatedness as a foundation for self
      definition in recovery from psychosis.

PMID- 15554810
TI  - Sibling perspectives on severe mental illness: reflections on self and family.
AB  - Through focus group interviews, participants were asked to describe the impact
      over time of having a sibling with severe mental illness. Transcript content was
      then organized into categories and overarching themes using grounded-theory
      analysis. Respondents' personal and interpersonal experiences are presented,
      along with suggestions for professional outreach and further research.

PMID- 15554811
TI  - Child Holocaust survivors as parents: a transgenerational perspective.
AB  - Children of Holocaust survivors frequently point out problems associated with
      having been raised by survivor parents. However, large-scale studies demonstrate
      that both Holocaust survivors and their children function within the normal
      range. This study addresses relationship issues between the younger survivors and
      their children. It does not compare them with nonsurvivor families, who may
      exhibit similar patterns. We found wide gaps between how child survivor parents
      and their children viewed parental expectations and behaviors. These
      discrepancies are described as 4 paradoxes.

PMID- 15554812
TI  - Elementary school children's responses 3 months after the September 11 terrorist
      attacks: a study in Washington, DC.
AB  - This study examined the responses of elementary school children in Washington,
      DC, to the September 11 terrorist attacks. Parents (primarily mothers) of
      children in kindergarten through Grade 6 and children in Grades 4 to 6, including
      47 matched parent-child pairs, completed questionnaires regarding exposure,
      stress reactions, and constructive actions taken 3 months after the attacks.
      Parent reports and, to an even greater extent, children's self-reports revealed
      high levels of negative reactions to the attacks on behalf of the children. These
      reactions were best understood in the context of their exposure to the attacks,
      primarily through television news, and the reactions of and coping assistance
      provided by their parents. Implications for school personnel, health care
      professionals, and intervention efforts are discussed.

PMID- 15554813
TI  - Stigmatization, discrimination, and mental health: the impact of multiple
      identity status.
AB  - The authors present the empirical characteristics of the Experience of
      Discrimination Scale (EDS) using baseline data from the Center for Mental Health
      Services-funded, multisite Consumer Operated Services Project. Specific
      hypotheses focused on the influence of multiple identity status on reports of
      discrimination. Data indicated that discrimination caused by mental disability
      was associated with level of psychiatric symptoms and perceived social rejection
      as a result of mental illness, whereas discrimination for other reasons was
      associated with broader quality of life and social interaction indicators. The
      clinical and policy implications of findings are discussed.

PMID- 15554814
TI  - Ecodevelopmental HIV prevention programs for Hispanic adolescents.
AB  - The purpose of this article is to illustrate how an ecodevelopmental perspective
      on risk and protection can be applied to the study and prevention of unsafe
      sexual behavior in Hispanic immigrant adolescents. Special attention is given to
      culturally based ecodevelopmental risk and protective processes that may
      influence unsafe sexual behavior among Hispanic adolescents. Principles for
      designing prevention programs to offset these risks are offered on the basis of
      an ecodevelopmental HIV prevention program that has been developed and is
      currently being tested.

PMID- 15554815
TI  - Multidimensional self-esteem and alcohol use among Mexican American and White non
      Latino adolescents: concurrent and prospective effects.
AB  - Self-esteem was evaluated among Mexican American and White non-Latino
      adolescents. Three dimensions of self-esteem-(a) self-confidence, (b) competence,
      and (c) social acceptance-were assessed for concurrent and longitudinal
      relationships to alcohol use. Various concurrent relationships were found between
      dimensions of self-esteem and alcohol use. Only 1 prospective effect was found,
      among Mexican American female adolescents, indicating that prior poor self
      confidence predicts higher levels of alcohol use.

PMID- 15554816
TI  - Protecting the health and welfare of staff, victims, and witness: report of a
      seminar at the International Criminal Court.

PMID- 15554817
TI  - Transracial, same-race adoptions, and the need for multiple measures of
      adolescent adjustment.
AB  - Using a multimeasure approach, the current study investigated 12 indices of
      academic, familial, psychological, and health outcomes for 4 groups of
      transracial and same-race adopted adolescents. A secondary analysis of the
      National Longitudinal Study of Adolescent Health data showed that Asian
      adolescents adopted by White parents had both the highest grades and the highest
      levels of psychosomatic symptoms, whereas Black adolescents adopted by Black
      parents reported the highest levels of depression. Intriguingly, and by contrast,
      Black adoptees reported higher levels of self-worth than non-Black adoptees. The
      implications of the findings for future investigations of transracial adoption
      are discussed.

PMID- 15554818
TI  - The role of impulsivity in children's estimation of physical ability:
      implications for children's unintentional injury risk.
AB  - Unintentional injuries are the leading cause of pediatric mortality. One factor
      that appears to predict injury risk is children's overestimation of physical
      ability. Fifty-seven 6-year-olds judged their ability to complete basic physical
      tasks. Half the sample was required to wait 7 s before judging their ability; the
      other half was permitted to judge immediately. There were no differences in
      ability estimation accuracy between the 2 groups, suggesting that the institution
      of a forced decision latency does not increase children's ability estimation
      accuracy. Replicating previous work, children tended to overestimate their
      ability, and overestimation of ability was related to history of unintentional
      injury. Possible explanations for the null finding are offered, and implications
      to injury prevention and future research are discussed.

PMID- 15554820
TI  - Sheldon Cohen: award for distinguished scientific contributions.

PMID- 15554821
TI  - Social relationships and health.

PMID- 15554822
TI  - E. Mavis Hetherington: award for distinguished scientific contributions.

PMID- 15554823
TI  - Richard M. Shiffrin: award for distinguished scientific contributions.

PMID- 15554825
TI  - Edward Taub: award for distinguished scientific applications of psychology.

PMID- 15554826
TI  - Harnessing brain plasticity through behavioral techniques to produce new
      treatments in neurorehabilitation.

PMID- 15554828
TI  - Edith Chen: award for distinguished scientific early career contributions to
      psychology.

PMID- 15554829
TI  - Gregory E. Miller: award for distinguished scientific early career contributions
      to psychology.

PMID- 15554830
TI  - Elena L. Grigorenko: award for distinguished scientific early career
      contributions to psychology.

PMID- 15554831
TI  - Thomas G. O'Connor: award for distinguished scientific early career contributions
      to psychology.

PMID- 15554832
TI  - Jenny R. Saffran: award for distinguished scientific early career contributions
      to psychology.

PMID- 15554833
TI  - Eric Stice: award for distinguished scientific early career contributions to
      psychology.

PMID- 15554834
TI  - Klaus Zuberbuhler: award for distinguished scientific early career contributions
      to psychology.

PMID- 15554836
TI  - Dante Cicchetti: award for distinguished senior career contributions to
      psychology in the public interest.

PMID- 15554837
TI  - An odyssey of discovery: lessons learned through three decades of research on
      child maltreatment.

PMID- 15554838
TI  - Susan Limber: award for distinguished early career contributions to psychology in
      the public interest.

PMID- 15554840
TI  - Thomas J. Coates: award for distinguished contributions to research in public
      policy.

PMID- 15554841
TI  - A plan for the next generation of HIV prevention research: seven key policy
      investigative challenges.

PMID- 15554843
TI  - Derald Wing Sue: award for distinguished career contributions to education and
      training.

PMID- 15554844
TI  - Whiteness and ethnocentric monoculturalism: making the "invisible" visible.

PMID- 15554845
TI  - Nadine J. Kaslow: award for distinguished contributions to education and
      training.

PMID- 15554846
TI  - Competencies in professional psychology.

PMID- 15554848
TI  - Emil R. Rodolfa: award for distinguished contributions of applications of
      psychology to education and training.

PMID- 15554850
TI  - Cortney S. Warren: Psi Chi/APA Edwin B. Newman graduate research award.

PMID- 15554852
TI  - Robert J. Gatchel: award for distinguished professional contributions to applied
      research.

PMID- 15554853
TI  - Comorbidity of chronic pain and mental health disorders: the biopsychosocial
      perspective.

PMID- 15554855
TI  - Miki Paul: award for distinguished professional contributions to independent or
      institutional practice in the private sector.

PMID- 15554856
TI  - Clinical implications in healing from domestic violence: a case study.

PMID- 15554858
TI  - Rodney R. Baker: award for distinguished professional contributions to practice
      in the public sector.

PMID- 15554860
TI  - Tonia L. Nicholls: APA/APAGS award for distinguished graduate student in
      professional psychology.

PMID- 15554862
TI  - Ronald P. Rohner: award for distinguished contributions to the international
      advancement of psychology.

PMID- 15554863
TI  - The parental "acceptance-rejection syndrome": universal correlates of perceived
      rejection.

PMID- 15554865
TI  - Chris E. Stout: international humanitarian award.

PMID- 15554866
TI  - Global initiatives.

PMID- 15554870
TI  - Sodium-lithium countertransport and the Gly460-->Trp alpha-adducin polymorphism
      in essential hypertension.
AB  - A polymorphism of the alpha-subunit of adducin, Gly460-->Trp, may affect membrane
      ion transport and be associated with human EH (essential hypertension). The alpha
      adducin Gly460-->Trp polymorphism was determined in 242 NC (normal controls) and
      73 patients with EH and was related to the membrane ion transport marker in EH,
      erythrocyte Na/LiCT (sodium-lithium countertransport), in a subgroup of these
      subjects. The Km for external sodium was lower in patients with EH than NC. The
      Km of the Trp allele was lower than with the Gly/Gly genotype [NC, 105+/-6
      compared with 88+/-5 mmol Na/l respectively (P=0.05); patients with EH, 76+/-5
      compared with 64+/-4 mmol Na/l respectively (P=0.06)]. The Km was lower in
      patients with EH than NC for any adducin genotype. Thiol alkylation with NEM (N
      ethylmaleimide) caused a decrease in Km in NC, but not in patients with EH. With
      a Trp allele, NEM lowered Km less in NC (-20 compared with -35) and increased it
      in patients with EH (+24 compared with +3; P=0.007 for genotype effect). Thiol
      alkylation with NEM caused an increase in Vmax in patients with EH but not in NC.
      With a Trp allele, NEM increased Vmax substantially in patients with EH (+0.12
      compared with +0.03) but did not cause a decrease in NC (+0.02 compared with 
      0.06; P=0.007 for genotype effect). In conclusion, the Gly460-->Trp polymorphism
      of alpha-adducin modifies the kinetics of Na/LiCT. The effect of this genotype is
      different in patients with EH compared with NC and it does not explain the
      abnormal kinetics in patients with EH. The Trp allele was not associated with
      disease in the population studied. Several cytoskeletal proteins may interact
      with adducin in the overall phenotype of EH.

PMID- 15554871
TI  - Effects of a dual endothelin-1 receptor antagonist on airway obstruction and
      acute lung injury in sheep following smoke inhalation and burn injury.
AB  - Studies have suggested that ET-1 (endothelin-1) is associated with lung injury,
      airway inflammation and increased vascular permeability. In the present study we
      have tested the hypothesis that treatment with a dual ET-1 receptor antagonist
      will decrease airway obstruction and improve pulmonary function in sheep with
      combined S+B (smoke inhalation and burn) injury. Twelve sheep received S+B injury
      using the following protocol: six sheep were treated with tezosentan, an ETA and
      ETB receptor antagonist, and six sheep received an equivalent volume of vehicle.
      Physiological and morphological variables were assessed during the 48 h study
      period and at the end of the study. There was no statistically significant
      difference in the PaO2/FiO2 (partial pressure of O2 in arterial blood/fraction of
      O2 in the inspired gas) ratio of the tezosentan-treated animals compared with
      controls; however, lung lymph flow was significantly higher (P<0.05) in the
      treated animals. PVRI (pulmonary vascular resistance index) was significantly
      reduced (P<0.05) in the tezosentan-treated animals. Assessment of NOx (nitric
      oxide metabolite) levels in plasma and lymph showed significantly elevated
      (P<0.05) levels in the tezosentan-treated animals compared with levels in
      untreated sheep. The degree of bronchial obstruction was similar in both treated
      and control sheep; however, bronchiolar obstruction was reduced in sheep treated
      with tezosentan. Histopathologically, no difference in the degree of parenchymal
      injury was detected. In conclusion, administration of a dual ET-1 receptor
      antagonist prevented an increase in PVRI after injury and reduced the degree of
      bronchiolar obstruction in sheep with S+B; however, treated sheep showed higher
      levels of NOx and increased lung lymph flow. Tezosentan treatment was ineffective
      in protecting against acute lung injury in this model.

PMID- 15554872
TI  - Nuclear envelope assembly is promoted by phosphoinositide-specific phospholipase
      C with selective recruitment of phosphatidylinositol-enriched membranes.
AB  - Nuclear envelope (NE) formation in a cell-free egg extract proceeds by precursor
      membrane vesicle binding to chromatin in an ATP-dependent manner, followed by a
      GTP-induced NE assembly step. The requirement for GTP in the latter step of this
      process can be mimicked by addition of bacterial PI-PLC [phosphoinositide
      (PtdIns)-specific phospholipase C]. The NE assembly process is here dissected in
      relation to the requirement for endogenous phosphoinositide metabolism, employing
      recombinant eukaryotic PI-PLC, inhibitors and direct phospholipid analysis using
      ESI-MS (electrospray ionization mass spectrometry). PtdIns (phosphatidylinositol)
      species analysis by ESI-MS indicates that the chromatin-bound NE precursor
      vesicles are enriched for specific PtdIns species. Moreover, during GTP-induced
      precursor vesicle fusion, the membrane vesicles become partially depleted of the
      PtdIns 18:0/20:4 species. These data indicate that eukaryotic PI-PLC can support
      NE formation, and the sensitivity to exogenous recombinant PtdIns-5-phosphatases
      shows that the endogenous PLC hydrolyses a 5-phosphorylated species. It is shown
      further that the downstream target of this DAG (diacylglycerol) pathway does not
      involve PKC (protein kinase C) catalytic function, but is mimicked by phorbol
      esters, indicating a possible engagement of one of the non-PKC phorbol ester
      receptors. The results show that ESI-MS can be used as a sensitive means to
      measure the lipid composition of biological membranes and their changes during,
      for example, membrane fusogenic events. We have exploited this and the
      intervention studies to illustrate a pivotal role for PI-PLC and its product DAG
      in the formation of NEs.

PMID- 15554873
TI  - Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process
      involving the scavenger receptor class B type I (SR-BI).
AB  - The carotenoid lutein is thought to play a role in the human eye and to protect
      against age-related macular degeneration. Lutein transport in the human intestine
      has not been characterized. We examined lutein transport processes using Caco-2
      TC-7 monolayers as a model for human intestinal epithelium. Purified lutein was
      mixed with phospholipids, lysophospholipids, cholesterol, mono-olein, oleic acid
      and taurocholate to obtain lutein-rich mixed micelles that mimicked those found
      under physiological conditions. The micelles were added to the apical side of
      Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 degrees C. Absorbed lutein,
      i.e. the sum of lutein recovered in the scraped cells and in the basolateral
      chamber, was quantified by HPLC. Transport rate was measured (i) as a function of
      time (from 15 to 60 min), (ii) as a function of micellar lutein concentration
      (from 1.5 to 15 microM), (iii) at 4 degrees C, (iv) in the basolateral to apical
      direction, (v) after trypsin pretreatment, (vi) in the presence of beta-carotene
      and/or lycopene, (vii) in the presence of increasing concentrations of antibody
      against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of
      increasing concentrations of a chemical inhibitor of the selective transfer of
      lipids mediated by SR-BI, i.e. BLT1 (blocks lipid transport 1). The rate of
      transport of lutein as a function of time and as a function of concentration was
      saturable. It was significantly lower at 4 degrees C than at 37 degrees C
      (approx. 50%), in the basal to apical direction than in the opposite direction
      (approx. 85%), and after trypsin pretreatment (up to 45%). Co-incubation with
      beta-carotene, but not lycopene, decreased the lutein absorption rate (approx.
      20%) significantly. Anti-SR-BI antibody and BLT1 significantly impaired the
      absorption rate (approx. 30% and 57% respectively). Overall, these results
      indicate that lutein absorption is, at least partly, protein-mediated and that
      some lutein is taken up through SR-BI.

PMID- 15554874
TI  - Fragmentation and dimerization of copper-loaded prion protein by copper-catalysed
      oxidation.
AB  - Prion protein consists of an N-terminal domain containing a series of octapeptide
      repeats with the consensus sequence PHGGGWGQ and a C-terminal domain composed of
      three alpha-helices and two short beta-strands. Several studies have shown that
      the N-terminal domain binds five Cu2+ ions. In the present study, we have
      investigated copper-catalysed oxidation of a recombinant mouse prion protein,
      PrP23-231. The copper-loaded PrP23-231 was found to be carbonylated by incubation
      with dopamine. Besides the formation of carbonyls, a cross-linked species with
      the dimeric size and C-terminally truncated species were generated. These
      reactions were retarded in the presence of Cu+- and Cu2+-specific copper
      chelators, catalase, and SOD (superoxide dismutase), but not in the presence of
      various bivalent metal ions. Together, these results indicate that the copper
      bound to prion protein undergoes catalytic cycling in the presence of
      catecholamines and causes the oxidation of the protein.

PMID- 15554876
TI  - Comparative analysis of the pathogenic mechanisms associated with the G8363A and
      A8296G mutations in the mitochondrial tRNA(Lys) gene.
AB  - Two mutations (G8363A and A8296G) in the mtDNA (mitochondrial DNA) tRNA(Lys) gene
      have been associated with severe mitochondrial diseases in a number of reports.
      Their functional significance, however, remains unknown. We have already shown
      that homoplasmic cybrids harbouring the A8296G mutation display normal oxidative
      phosphorylation, although the possibility of a subtle change in mitochondrial
      respiratory capacity remains an open issue. We have now investigated the
      pathogenic mechanism of another mutation in the tRNA(Lys) gene (G8363A) by
      repopulating an mtDNA-less human osteosarcoma cell line with mitochondria
      harbouring either this genetic variant alone or an unusual combination of the two
      mutations (A8296G+G8363A). Cybrids homoplasmic for the single G8363A or the
      A8296G+G8363A mutations have defective respiratory-chain enzyme activities and
      low oxygen consumption, indicating a severe impairment of the oxidative
      phosphorylation system. Generation of G8363A cybrids within a wild-type or the
      A8296G mtDNA genetic backgrounds resulted in an important alteration in the
      conformation of the tRNA(Lys), not affecting tRNA steady-state levels. Moreover,
      mutant cybrids have an important decrease in the proportion of amino-acylated
      tRNA(Lys) and, consequently, mitochondrial protein synthesis is greatly
      decreased. Our results demonstrate that the pathogenicity of the G8363A mutation
      is due to a change in the conformation of the tRNA that severely impairs
      aminoacylation in the absence of changes in tRNA stability. The only effect
      detected in the A8296G mutation is a moderate decrease in the aminoacylation
      capacity, which does not affect mitochondrial protein biosynthesis.

PMID- 15554875
TI  - The ADAMTS metalloproteinases.
AB  - The ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are
      a group of proteases that are found both in mammals and invertebrates. Since the
      prototype ADAMTS-1 was first described in 1997, there has been a rapidly
      expanding body of literature describing this gene family and the proteins they
      encode. The complete human family has 19 ADAMTS genes, together with three
      members of a newly identified subgroup, the ADAMTSL (ADAMTS-like) proteins, which
      have several domains in common with the ADAMTSs. The ADAMTSs are extracellular,
      multidomain enzymes whose known functions include: (i) collagen processing as
      procollagen N-proteinase; (ii) cleavage of the matrix proteoglycans aggrecan,
      versican and brevican; (iii) inhibition of angiogenesis; and (iv) blood
      coagulation homoeostasis as the von Willebrand factor cleaving protease. Roles in
      organogenesis, inflammation and fertility are also apparent. Recently, some
      ADAMTS genes have been found to show altered expression in arthritis and various
      cancers. This review highlights progress in understanding the structural
      organization and functional roles of the ADAMTSs in normal and pathological
      conditions.

PMID- 15554877
TI  - Drosophila melanogaster NEP2 is a new soluble member of the neprilysin family of
      endopeptidases with implications for reproduction and renal function.
AB  - The mammalian neprilysin (NEP) family members are typically type II membrane
      endopeptidases responsible for the activation/inactivation of neuropeptides and
      peptide hormones. Differences in substrate specificity and subcellular
      localization of the seven mammalian NEPs contribute to their functional
      diversity. The sequencing of the Drosophila melanogaster genome has revealed a
      large expansion of this gene family, resulting in over 20 fly NEP-like genes,
      suggesting even greater diversity in structure and function than seen in mammals.
      We now report that one of these genes (Nep2) codes for a secreted endopeptidase
      with a highly restricted pattern of expression. D. melanogaster NEP2 is expressed
      in the specialized stellate cells of the renal tubules and in the cyst cells that
      surround the elongating spermatid bundles in adult testis, suggesting roles for
      the peptidase in renal function and in spermatogenesis. D. melanogaster NEP2 was
      found in vesicle-like structures in the syncytial cytoplasm of the spermatid
      bundles, suggesting that the protein was acquired by endocytosis of protein
      secreted from the cyst cells. Expression of NEP2 cDNA in D. melanogaster S2 cells
      confirmed that the peptidase is secreted and is only weakly inhibited by
      thiorphan, a potent inhibitor of human NEP. D. melanogaster NEP2 also differs
      from human NEP in the manner in which the peptidase cleaves the tachykinin,
      GPSGFYGVR-amide. Molecular modelling suggests that there are important structural
      differences between D. melanogaster NEP2 and human NEP in the S1' and S2' ligand
      binding subsites, which might explain the observed differences in inhibitor and
      substrate specificities. A soluble isoform of a mouse NEP-like peptidase is
      strongly expressed in spermatids, suggesting an evolutionarily conserved role for
      a soluble endopeptidase in spermatogenesis.

PMID- 15554880
TI  - A perspective on stem cells by a clinician.
AB  - Stem cell terminology has entered the lexicon of medical practitioners even
      though the application of harvesting stem cells to treat diseases other than
      haematological disorders is not yet a reality in clinical practice. All branches
      of medicine will be affected by the new technology, more so those related to
      regenerative cell-based therapy for disorders such as Parkinson's disease,
      Alzheimer's disease, multiple sclerosis and traumatic injuries to the nervous
      system. Endocrinology is not a branch of medicine that carries a burden of
      disease that merits priority for the early application of stem cell therapy once
      the technique becomes safe and practical to do so. However, the allied disorder
      of diabetes is, sine qua non, an ideal example of how stem cell therapy has the
      potential to cure a chronic disabling condition. It is logical therefore to have
      included a number of articles on stem cells in this special issue of this
      journal, publishing papers on a range of endocrine-related topics.

PMID- 15554878
TI  - A proteolytic fragment of Mcl-1 exhibits nuclear localization and regulates cell
      growth by interaction with Cdk1.
AB  - Mcl-1 (myeloid cell leukaemia-1) is a Bcl-2 family member with short-term pro
      survival functions but whose other functions, demonstrated by embryonic lethality
      of knockout mice, do not involve apoptosis. In the present study, we show a cell
      cycle-regulatory role of Mcl-1 involving a shortened form of the Mcl-1
      polypeptide, primarily localized to the nucleus, which we call snMcl-1. snMcl-1
      interacts with the cell-cycle-regulatory protein Cdk1 (cyclin-dependent kinase 1;
      also known as cdc2) in the nucleus, and Cdk1 bound to snMcl-1 was found to have a
      lower kinase activity. The interaction with Cdk1 occurs in the absence of its
      cyclin partners and is enhanced on treatment of cells with G2/M blocking agents,
      but not by G1/S blocking. The snMcl-1 polypeptide is present during S and G2
      phases and is negligible in G1. Overexpression of human Mcl-1 in a murine myeloid
      progenitor cell line resulted in a lower rate of proliferation. Furthermore, Mcl
      1-overexpressing cells had lower total Cdk1 kinase activity compared with
      parental cells, in both anti-Cdk1 and anti-cyclin B1 immunoprecipitates. The
      latter results suggest that binding to snMcl-1 alters the ability of Cdk1 to bind
      its conventional partner, cyclin B1. Given the important role of Cdk1 in
      progression through G2 and M phases, it is probable that the inhibition of Cdk1
      activity accounts for the inhibitory effect of Mcl-1 on cell growth.

PMID- 15554881
TI  - Stem cell research: immortality or a healthy old age?
AB  - Stem cell research holds the promise of treatments for many disorders resulting
      from disease or trauma where one or at most a few cell types have been lost or do
      not function. In combination with tissue engineering, stem cells may represent
      the greatest contribution to contemporary medicine of the present century.
      Progress is however being hampered by the debate on the origin of stem cells,
      which can be derived from human embryos and some adult tissues. Politics,
      religious beliefs and the media have determined society's current perception of
      their relative value while the ethical antipathy towards embryonic stem cells,
      which require destruction of a human embryo for their derivation, has in many
      countries biased research towards adult stem cells. Many scientists believe this
      bias may be premature and basic research on both cell types is still required.
      The media has created confusion about the purpose of stem cell research: treating
      chronic ailments or striving for immortality. Here, the scientific state of the
      art on adult and embryonic stem cells is reviewed as a basis for a debate on
      whether research on embryonic stem cells is ethically acceptable.

PMID- 15554882
TI  - On the origin, use and destination of human embryos.
AB  - The moral acceptability or non-acceptability of the use of human embryos in
      research raises questions on several philosophical levels. The mixing-up of these
      levels results in strongly defended and endless debates. In this contribution,
      arguments on three levels will be discussed, the ontological, the practical and
      instrumental and the level of human relationships. It is concluded that, on the
      latter level, the moral problems of the other two are significant, but not
      conclusive. The decision to allow or to ban research with human embryos is
      charged with full human responsibility.

PMID- 15554883
TI  - An ontological view of the human embryo. A paradigm.
AB  - In the present paper I analyze the existing paradigms explaining the ontological
      status of the organisms originating during a given developmental process and the
      potentiality these paradigms offer. These paradigms give us a hint of the
      ontological and ethical status of these organisms. It is described that during
      the history of human thought two theories have been developed to explain the
      origin of living organisms. One theory placed the world's origin and the origin
      of living organisms in a transcendent reality while the second stated that the
      growing complexity of these organisms was rooted in an internal 'dynamis' (the
      internal potential of a thing, generally a living thing, to acquire new
      properties) that is present in each one of them. These paradigms are analysed
      concluding that at the time they were formulated there was no formal
      understanding of the process of development because the emergence of novelties
      through evolution was not included in them. At that time growth and development
      were two aspects of the same thing. A critical turning point in biological and
      philosophical thinking was provided by the founders of the DNA paradigm as the
      program directing development. Due to new insights, a paradigm is presented here
      which includes the epigenesic information as an essential element of the program
      of development together with the DNA. The consequence of this paradigm is that
      the program of development is time- and space-dependent and that the biological
      elements which originate during the process are not preformed but adopt specific
      values. This way of thinking introduces new approaches to the analysis of the
      value of the human embryo with repercussions in the ethical discussions on
      research programs using embryonic stem cells.

PMID- 15554884
TI  - Role of thyroid hormone during early brain development.
AB  - The present comments are restricted to the role of maternal thyroid hormone on
      early brain development, and are based mostly on information presently available
      for the human fetal brain. It emphasizes that maternal hypothyroxinemia - defined
      as thyroxine (T4) concentrations that are low for the stage of pregnancy - is
      potentially damaging for neurodevelopment of the fetus throughout pregnancy, but
      especially so before midgestation, as the mother is then the only source of T4
      for the developing brain. Despite a highly efficient uterine-placental 'barrier'
      to their transfer, very small amounts of T4 and triiodothyronine (T3) of maternal
      origin are present in the fetal compartment by 4 weeks after conception, with T4
      increasing steadily thereafter. A major proportion of T4 in fetal fluids is not
      protein-bound: the 'free' T4 (FT4) available to fetal tissues is determined by
      the maternal serum T4, and reaches concentrations known to be of biological
      significance in adults. Despite very low T3 and 'free' T3 (FT3) in fetal fluids,
      the T3 generated locally from T4 in the cerebral cortex reaches adult
      concentrations by midgestation, and is partly bound to its nuclear receptor.
      Experimental results in the rat strongly support the conclusion that thyroid
      hormone is already required for normal corticogenesis very early in pregnancy.
      The first trimester surge of maternal FT4 is proposed as a biologically relevant
      event controlled by the conceptus to ensure its developing cerebral cortex is
      provided with the necessary amounts of substrate for the local generation of
      adequate amounts of T3 for binding to its nuclear receptor. Women unable to
      increase their production of T4 early in pregnancy would constitute a population
      at risk for neurological disabilities in their children. As mild-moderate iodine
      deficiency is still the most widespread cause of maternal hypothyroxinemia in
      Western societies, the birth of many children with learning disabilities may
      already be preventable by advising women to take iodine supplements as soon as
      pregnancy starts, or earlier if possible.

PMID- 15554885
TI  - Molecular genetic defects in congenital hypothyroidism.
AB  - Recently molecular genetic defects in some cases of congenital hypothyroidism
      (CH) as well as of rare cases of central hypothyroidism have been identified.
      These studies have led to the description of so far unexplained forms of these
      disorders. In some patients with CH early diagnosis by newborn screening and
      early treatment was not able to lead to a normal mental development. This could
      subsequently be explained by molecular defects of transcription factors (FOXE
      1/FKHL15, NKX2.1) which are important not only for the embryonic development of
      the thyroid gland but also for other organs including the central nervous system
      (CNS). These findings will help in understanding the critical role of thyroid
      hormones in the pre-and postnatal CNS development. However, many questions
      regarding the molecular defects and their consequences in the majority of
      patients with CH still remain open and will be addressed in this article.

PMID- 15554886
TI  - The sequelae of untreated maternal hypothyroidism.
AB  - The concept that gestational subclinical hypothyroidism could have deleterious
      effects on the intellectual outcome of progeny was championed more than three
      decades ago by Evelyn Man in a series of publications. Her studies lay fallow
      until the Spanish group directed by Morreale de Escobar and the Dutch group
      headed by Vulsma provided the rationale for her results. Although the findings of
      the Spanish and Dutch groups elucidated the pathophysiologic basis for Man's
      conclusions, questions remained regarding the reliability of her biochemical
      measurements and possible bias in patient selection. In view of the uncertainty
      surrounding the validity of Man's work, we decided to try to confirm her
      findings. Our initial goal was to obtain an estimate of the prevalence of
      subclinical hypothyroidism in an unselected population living in New England. We
      accomplished this with two separate prospective studies involving 12 000 pregnant
      women residing in Maine. We found that 2.3% had TSH concentrations of >6.0 mU/l
      and 0.3% had TSH values of >12 mU/l at 17 weeks' gestation. We next did a
      retrospective study, utilizing sera that had been stored at -20 degrees C for 8
      years, obtained in week 17 of gestation from 25 000 women. We identified 62 women
      with subclinical hypothyroidism and 124 matched controls. Fourteen of the
      hypothyroid mothers had been diagnosed and treated before and during pregnancy on
      a dosage of thyroxine that was unchanged. WISC IQs of the offspring of the 124
      control and 62 hypothyroid mothers were determined at 8+/-0.5 years. The mean and
      s.d. of IQs of the children of the 124 control and of the 14 treated hypothyroid
      mothers were significantly higher than those of the children of the 48 untreated
      hypothyroid women. More than twice as many children of the untreated mothers had
      IQs of >1 s.d. below the control mean, and four times as many of the children had
      IQs 2 s.d. below the control mean, as did the children of the controls. A
      comparison of the mean hormonal values of the treated and untreated mothers at 17
      weeks showed no significant difference in any of the biochemical markers. We
      surmise that the circulating level of thyroxine was normal in the treated mothers
      at a critical time before 17 weeks' gestation, but by 17 weeks it was
      insufficient to meet the growing demands of pregnancy. Treatment should begin as
      early as possible in pregnancy with the goal of maintaining free thyroxine
      (FT(4)) in the upper half of the normal reference range and TSH in the lower half
      of the normal reference range. In view of these data, we believe that all
      pregnant women should be screened for hypothyroidism as early in pregnancy as
      possible (or even before conception). To be cost-effective, screening programs
      should be based on those designed for congenital hypothyroidism, in which filter
      paper blood specimens are forwarded to regional laboratories for thyroid function
      determinations.

PMID- 15554887
TI  - Prenatal glucocorticoids and long-term programming.
AB  - Epidemiological evidence suggests that low birth weight is associated with an
      increased risk of cardiovascular, metabolic and neuroendocrine disorders in adult
      life. Glucocorticoid administration during pregnancy reduces offspring birth
      weight and alters the maturation of the lung and other organs. We hypothesised
      that prenatal exposure to excess glucocorticoids or stress might represent a
      mechanism linking foetal growth with adult pathophysiology. In rats, birth weight
      is reduced following prenatal exposure to the synthetic steroid dexamethasone,
      which readily crosses the placenta, or to carbenoxolone, which inhibits 11beta
      hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the physiological feto
      placental 'barrier' to maternal glucocorticoids. As adults, the offspring exhibit
      permanent hypertension, hyperglycaemic, increased hypothalamic-pituitary-adrenal
      (HPA) axis activity and behaviour reminiscent of anxiety. Physiological
      variations in placental 11beta-HSD2 activity correlate directly with foetal
      weight. In humans, 11beta-HSD2 gene mutations cause low birth weight. Moreover,
      low-birth-weight babies have higher plasma cortisol levels throughout adult life,
      indicating HPA axis programming. The molecular mechanisms may reflect permanent
      changes in the expression of specific transcription factors, key among which is
      the glucocorticoid receptor (GR) itself. The differential programming of the GR
      in different tissues reflects effects upon one or more of the multiple tissue
      specific alternate first exons/promoters of the GR gene. Overall, the data
      suggest that both pharmacological and physiological exposure prenatally to excess
      glucocorticoids programmes cardiovascular, metabolic and neuroendocrine disorders
      in adult life.

PMID- 15554888
TI  - Prenatal treatment of congenital adrenal hyperplasia.
AB  - In foetuses at risk of virilising congenital adrenal hyperplasia (CAH), prenatal
      treatment can be offered by administration of dexamethasone (DEX) via the mother,
      in order to suppress foetal adrenal androgen oversecretion and prevent genital
      malformations. The first treated cases were described 20 years ago, and several
      hundred pregnancies have been reported since. There is a consensus that the
      treatment effectively prevents or reduces virilisation, but opinions regarding
      its safety differ. Rare adverse events have been reported in treated children,
      but no harmful effect has been documented that can be clearly attributed to the
      treatment. However, few treated foetuses have been followed until adolescence.
      Animal studies and epidemiological data point to various adverse effects of
      excess glucocorticoids on the developing foetus. In order to prevent virilisation
      effectively in females affected with CAH, the prenatal treatment needs to be
      instituted in the early first trimester, before prenatal diagnosis is possible.
      Thus, a majority of treated foetuses will receive DEX unnecessarily. The PREDEX
      study was initiated in Stockholm in 1999 as an open, controlled, non-randomised,
      multicentre trial. Participating centres are Stockholm, Bergen, Kuopio, Warsaw,
      London, Lyon and Barcelona. The study has been approved by the ethics committees
      in each country. The purpose of PREDEX is to evaluate prospectively the prenatal
      treatment regarding efficacy in preventing virilisation as well as to study its
      safety for both mothers and treated children. Children are followed until 18
      years of age and a wide range of physiological, metabolic and developmental
      parameters are considered. In Sweden, treatment is not offered outside the frames
      of the trial.

PMID- 15554889
TI  - Neonatal screening for congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is well suited for newborn screening, as it
      is a common and potentially fatal disease which can be easily diagnosed by a
      simple hormonal measurement in blood. Moreover, early recognition and treatment
      can prevent severe salt wasting, dehydration and death and shorten the time of
      male sex assignment in virilised females.In screening programmes, 17alpha
      hydroxyprogesterone (17OHP) is measured in filter paper blood spots obtained by a
      heel puncture preferably between 2 and 4 days after birth. Three assay techniques
      are utilised for initial screening: radio-immunoassay (USA), enzyme-linked
      immunosorbent assay (Japan) and time-resolved fluoro-immunoassay (Europe).
      Preterm newborns have higher 17OHP concentrations in serum than babies born at
      term. Therefore, cut-off levels are based on gestational age (in Japan and
      Europe) or on birth weight (in the USA). There is a considerable variation in cut
      off levels from one programme to another. This is most likely due to the
      different antibodies and reagents used, varying thickness and density of filter
      paper used for sample collection and, most significantly, the characteristics of
      the reference population (in terms of birth weight and gestational age). More
      than 30 million newborns have been screened. The prevalence of CAH in the USA and
      Europe is approximately 1:15 000-16 000, and slightly lower in Japan (1:19 000).
      In general, severe salt wasting can be prevented, but there is a remarkable
      variation in the number of false-positives and false-negatives among the various
      programmes. Ongoing refinement of cut-off levels is needed to improve specificity
      and sensitivity.

PMID- 15554890
TI  - Classic congenital adrenal hyperplasia and puberty.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders
      resulting from deficiency of one of the five enzymes required for synthesis of
      cortisol in the adrenal cortex. The most common form of the disease is classic 21
      hydroxylase deficiency, which is characterized by decreased synthesis of
      glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and
      impaired development and function of the adrenal medulla. The clinical management
      of classic 21-hydroxylase deficiency is often suboptimal, and patients are at
      risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism.
      Limitations of current medical therapy include the inability to control
      hyperandrogenism without employing supraphysiologic doses of glucocorticoid,
      hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic
      hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior
      pituitary. Puberty imposes increased difficulty in attaining adrenocortical
      suppression despite optimal substitution therapy and adherence to medical
      treatment. Alterations in the endocrine milieu at puberty may influence cortisol
      pharmacokinetics and, consequently, the handling of hydrocortisone used as
      replacement therapy. Recent studies have demonstrated a significant increase in
      cortisol clearance at puberty and a shorter half-life of free cortisol in
      pubertal females compared with males. Furthermore, children with classic CAH have
      elevated fasting serum insulin concentrations and insulin resistance. The latter
      may further enhance adrenal and/or ovarian androgen secretion, decrease the
      therapeutic efficacy of glucocorticoids and contribute to later development of
      the metabolic syndrome and its complications.

PMID- 15554891
TI  - New insights in the genetics of isolated hypogonadotropic hypogonadism.
AB  - Isolated gonadotropic deficiency or isolated hypogonadotropic hypogonadism is
      defined as a low sexual hormone secretion by the gonads associated with low LH
      and FSH plasma levels. Kallmann syndrome is defined as a congenital isolated
      gonadotropic deficiency associated with anosmia whereas the phenotype of the
      idiopathic form is limited to the gonadotropic axis. For several years, it has
      been known that mutations of the KAL-1 gene or loss-of-function mutations of GnRH
      receptor did not explain all familial cases of isolated gonadotropic deficiency
      with or without anosmia. Thus the existence of other genes playing a major role
      in the physiology of the gonadotropic axis was highly suggested. In 2003,
      fibroblast growth factor receptor 1 (FGFR1) and GPR54 were shown to be two of
      these genes. FGFR1 loss-of-function mutations were reported in Kallmann syndrome
      whereas inactivating mutations of GPR54 were described in the idiopathic form of
      the gonadotropic deficiency. These genetic studies have opened up a new chapter
      in the physiology and the pharmacology of the gonadotropic axis.

PMID- 15554892
TI  - Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism-
      diagnostic and therapeutic aspects.
AB  - BACKGROUND: Puberty is the result of reactivation of the gonadotropin releasing
      hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the
      hypothalamus, which stimulates the gonadotropic cells of the pituitary to
      synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often
      the result of GnRH deficiency. The clinical picture is characterized by the
      absence of pubertal development and infertility. It is difficult to differentiate
      HH from delayed puberty since low gonadotropin and low testosterone levels are
      found in both conditions. We hypothesized that long-term GnRH administration may
      differentiate between the two conditions by a difference in the increase of
      gonadotropins, the idea being that in normal delayed puberty the pituitary of the
      patient has been primed with GnRH during the fetal and early postnatal period.
      PATIENTS: Seventeen adolescents suspected of having hypogonadotropic hypogonadism
      were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis
      of these patients is known and the results of the long-term GnRH stimulation have
      been evaluated according to the present diagnosis. RESULTS: The results show that
      the increase in gonadotropins following GnRH treatment is similar in both
      conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be
      distinguished from hypogonadotropic hypogonadism using long-term GnRH
      stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for
      the induction of puberty. Unlike testosterone it has the advantage of stimulation
      of testicular growth and fertility, as well as virilization, in males. We have
      treated 68 male patients with HH with pulsatile GnRH. The results show testicular
      growth and virilization in all the patients and spermatogenesis in 58 patients.
      Wearing a portable pump is cumbersome. However, the patients were very motivated
      and adapted very easily to this inconvenience. When spermatogenesis had
      developed, GnRH treatment was changed to human chorionic gonadotropin (hCG)
      administration 1-2 times per week intramuscularly or subcutaneously. During hCG
      therapy spermatogenesis was maintained or even improved. At least ten patients
      fathered children. CONCLUSION: Pulsatile GnRH cannot distinguish between a normal
      delayed puberty and a hypothalamic defect in still prepubertal patients.
      Pulsatile GnRH offers an appropriate way to initiate testicular growth including
      virilization and fertility in males with hypogonadotropic hypogonadism.

PMID- 15554893
TI  - The regulation of GH secretion by sex steroids.
AB  - Gonadal sex steroids modulate GH synthesis and secretion with effects on both the
      hypothalamus and anterior pituitary. In the post-pubertal animal, androgens and
      oestrogens modulate hypothalamic somatostatin (SS) and GHRH synthesis
      respectively. These effects may be direct as SS neurons express the androgen
      receptor and many GHRH neurons are oestrogen receptor positive. The neonatal
      steroid environment modulates the number of GHRH neurons in the adult
      hypothalamus, as well as their responsivity to post-pubertal steroids.
      Furthermore, both neonatal and post-pubertal steroids modulate hypothalamic
      synaptic organisation affecting the number of synaptic inputs and the morphology
      of glial cells. This in turn has important effects on the ability of the
      hypothalamus to drive the secretory pulsatility of anterior pituitary hormone
      release. At the level of the somatotroph, androgens and oestrogens have been
      reported to stimulate, inhibit or have no effect on GH synthesis. In primary
      cultures, we found no effect of either androgens or oestrogens on GH mRNA levels.
      However, the sex steroid environment significantly modified the response of
      somatotrophs to SS. Furthermore, males have more somatotrophs compared with
      female rats and this partially depends on the neonatal sex steroid environment.
      In conclusion, sex steroids have both organisational and activational effects on
      the GH axis. These effects range from modulating the number of hypothalamic
      neurons controlling GH secretion, their responsiveness to later steroids, and the
      synaptic connectivity and neuropeptide production, to modulation of somatotroph
      numbers in the anterior pituitary and their responsiveness to inputs controlling
      GH synthesis and secretion.

PMID- 15554894
TI  - Can we increase adolescent growth?
AB  - Adolescent growth represents 15-20% of adult height and has been the focus of
      several treatment interventions, aiming at increasing the amplitude of the
      adolescent spurt. Importantly, pre- and early puberty are times when patients and
      families seek medical help and when estimates of adult height are more accurate
      than in younger children. We review the current approaches aimed at increasing
      pubertal growth in short children and knowledge about their results and risks.
      GnRH agonists, when used outside the context of precocious puberty, induce a
      modest gain (4 cm) when they are used for more than 3 years. Their effects on
      bone mass, body composition and possibly on psychosocial parameters limit their
      use. Several trials have now shown that GH can increase adult height of short
      adolescents with idiopathic short stature or born small for gestational age.
      However, the amplitude of the effect is modest and of dubious clinical
      significance. Lastly, the association of both approaches is rather popular among
      pediatric endocrinologists but still lacks a definite demonstration of its
      efficacy. In conclusion, we have gained insight in the median effects of some of
      these treatments and overoptimistic initial expectations are now refocused.
      However, we still have a long way to go before we truly evaluate the factors
      affecting the variable individual responses to these treatments, their clinical
      significance and their cost-benefit balance.

PMID- 15554895
TI  - Growth, growth factors and diabetes.
AB  - Type 1 diabetes mellitus (T1DM) and other chronic diseases in children are well
      known to adversely affect linear growth and pubertal development. In the years
      immediately following the introduction of insulin therapy, short stature was
      consistently reported in children with T1DM. However, over the past 50 years
      significant improvement in the prognosis for growth and final height in children
      with diabetes has been achieved. Although pre-pubertal and post-pubertal growth
      are important phases in growth, puberty and its related hormonal changes
      represent a critical phase for growth gain and final height particularly in
      patients with T1DM. Growth impairment reported in diabetic patients is dependent
      on abnormalities in physiological bone growth and corresponds to abnormalities of
      the growth hormone-insulin-like growth-I (GH-IGF-I) axis. These alterations seem
      to be related to appropriate insulin levels and thereby to glycaemic control as
      judged by haemoglobin levels. Modern diabetes care, particularly intensified
      insulin regimens, might improve metabolic control in patients with T1DM,
      therefore preventing abnormalities of the GH-IGF-I axis and leading to normal
      growth and final height similar to that of their unaffected peers.

PMID- 15554896
TI  - The Avon Longitudinal Study of Parents and Children (ALSPAC)--study design and
      collaborative opportunities.
AB  - The Avon Longitudinal Study of Parents and Children (ALSPAC) is a population
      based study designed to understand the ways in which the physical and social
      environment interact, over time, with the genotype to affect health, behaviour
      and development. This information about causal interactions in common diseases
      and disorders will provide the basis on which future preventive interventions can
      be tested, especially in regard to people with specific genotypes. Whilst ALSPAC
      builds on data and hypotheses generated by earlier general population cohorts,
      its design offers special advantages, the most important being: enrolment in
      early pregnancy; banking of DNA from the children and parents (permitting genetic
      transmission tests and transgenerational imprinting studies); diverse physical,
      psychological and environmental measures; one geographical base (permitting
      medical record and school linkage; environmental measures in the home, and
      clinics for direct examination); annual hands-on examinations of the full cohort
      since age 7. The 14 541 enrolled pregnancies (expected date of delivery 1 April
      1991 to 31 December 1992) represented about 85% of the eligible population. The
      13 971 children who were still alive at age 12 months have been followed
      principally by questionnaires completed by a parent. Twelve years on,
      questionnaires are still being sent out to 11 300 families. The average
      questionnaire response rate from mothers is 79%. From age 7, annual examinations
      of both 'physical' and 'psychological' aspects have also been conducted on the
      children (approximately 8000 attend each 'clinic'). The quality of the data has
      proved high in validation studies and is maintained by collaboration with experts
      in each specialist field. The high participation rate ensures a viable study well
      into the future.

PMID- 15554897
TI  - The Avon Longitudinal Study of Parents and Children (ALSPAC): a resource for
      genetic epidemiology.
AB  - The Avon Longitudinal Study of Parents and Children (ALSPAC) has collected
      detailed phenotypic and environmental information from pregnancy onwards on
      approximately 14 000 babies born in 1991-1992. A DNA bank on over 10 000 mothers
      and children has been established with generic consent for (undisclosed) genetic
      analysis, and cell lines on both children and parents are planned. As a
      multigenerational population cohort unselected by disease, trait or exposure,
      ALSPAC is uniquely placed to explore the genetic and environmental determinants
      of adverse developmental responses and common disease. Added value for genetic
      epidemiology generally is the ability to detect distortion of the expected
      Mendelian 50:50 transmission of alleles to study subjects (e.g. due to
      differential loss of embryos of one genotype) or to test for heterosis, i.e.
      whether heterozygotes have a greater or lesser effect than either homozygote.
      Finally, phenome scans (a fixed format analysis of the associations between a
      genotype of interest and thousands of outcome variables from the cohort database)
      could be used as a screening tool to test whether certain classes of genetic
      variation have more impact than others on human health and development.

PMID- 15554898
TI  - Birth weight, infant growth and insulin resistance.
AB  - Size at birth and early postnatal growth rates are important determinants of
      human perinatal survival; they also predict the tempo of growth, adult height and
      long-term risks for obesity, type 2 diabetes and cardiovascular disease. Results
      from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) show that
      fetal growth is influenced by both fetal genes and maternal-uterine-placental
      factors. Important maternal-placental factors include parity, smoking and weight
      gain, but also maternal genetic factors in the mother or fetal placenta,
      including the mitochondrial DNA 16189 variant and H19. These maternal genetic
      factors particularly influence smaller, growth-restrained infants, as in first
      pregnancies. Fetal genes include the insulin gene (INS) VNTR (variable number of
      tandem repeat), which we recently confirmed to be associated with birth size and
      cord blood IGF-II levels; these fetal gene effects are more evident in the
      absence of maternal-uterine growth restraint. During postnatal life, the INS VNTR
      III/III genotype remains associated with body size, including body mass index and
      waist circumference, and also lower insulin sensitivity among girls. However, as
      at birth, significant gene-environment interactions are seen. Rapid 'catch-up'
      early postnatal weight gain follows maternal-uterine restraint, and strongly
      predicts later childhood obesity and insulin resistance; among these children,
      those with INS VNTR class I alleles are more obese. Genetic factors that
      influence early growth may have conferred some early survival advantage in human
      history during times of undernutrition. With abundant nutrition and rising
      obesity rates, these genetic factors and their interactions with maternal and
      childhood environmental factors that influence childhood growth may now
      contribute to the early development of adult disease risk. Their recognition may
      help the development of targeted early interventions to prevent the progression
      towards adult disease.

PMID- 15554899
TI  - The Avon Longitudinal Study of Parents and Children (ALSPAC)--a resource for the
      study of the environmental determinants of childhood obesity.
AB  - Childhood obesity is a major public health problem because the prevalence is
      increasing and because childhood obesity is associated with short- and long-term
      adverse consequences. By contributing to our understanding of the causes of
      childhood obesity epidemiological studies can help to inform preventive
      strategies. Prospective studies with all-of-life measures of exposures, objective
      measures of physical activity and more accurate measures of diet and body
      composition will be better able to identify modifiable environmental exposures
      that act cumulatively or at critical time periods across the lifecourse. The Avon
      Longitudinal Study of Parents and Children (ALSPAC) recruited around 14 000
      pregnant women with estimated dates of delivery between 1991 and 1992. The
      children have been followed-up in detail ever since and now constitute probably
      the most intensively studied cohort of children ever recruited. Recent analyses
      have identified important modifiable risk factors and further analyses based on
      more accurate measures of diet, activity and body composition should provide
      further insights.

PMID- 15554900
TI  - Sex 'n' drugs 'n' rock 'n' roll: the meaning and social consequences of pubertal
      timing.
AB  - This is a brief review of the normal changes in adolescent behaviour and the
      interplay between biology and social factors that occur at and around puberty, in
      an attempt to explain when this transition may become problematic The onset of
      puberty is a biological marker for an individual's transition from a non
      reproductive to a reproductive state. Adolescence is a normal developmental
      transition associated with clearly visible physical changes, reorganization and
      pruning of neuronal circuits in the brain and the occurrence of new behaviours
      and interests. It is a time when new life tasks (orientation towards peers of the
      other sex, romantic and sexual involvement and mastering an educational career)
      need to be mastered. Parent-child conflict increases and becomes more intense as
      the adolescent struggles for more independence while still requiring support.
      These normal changes can become problematic if biological and social expectations
      diverge e.g. entering puberty very early or very late. While early pubertal onset
      in boys is likely to have beneficial effects, in girls precocious pubertal timing
      may have a negative impact on body-image, affect (or emotional well-being) and
      sex-role expectations. Other individual biological predispositions and genetic
      endowment may interact with social factors (e.g. peers, parenting style,
      neighbourhood) making adolescence either an adaptive or a challenging transition.
      There is a lack of sufficiently large longitudinal studies that have been able to
      study this interaction between genetics, biology and social environment on
      adolescent development. The Avon Longitudinal Study of Parents and Children
      (ALSPAC) cohort provides a unique opportunity to investigate the impact of
      pubertal timing on social behaviour. Planned assessments and concepts are
      outlined.

PMID- 15554902
TI  - Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin
      regulated gene expression and liver failure.
AB  - The liver plays an important role in insulin-regulated glucose homoeostasis. To
      study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1)
      signalling pathway in mediating insulin's actions in the liver, we employed CRE
      recombinase/loxP technology to generate L(liver)-PDK1-/- mice, which lack
      expression of PDK1 in hepatocytes and in which insulin failed to induce
      activation of PKB in liver. The L-PDK1-/- mice were not insulin-intolerant,
      possessed normal levels of blood glucose and insulin under normal feeding
      conditions, but were markedly glucose-intolerant when injected with glucose. The
      L-PDK1-/- mice also possessed 10-fold lower levels of hepatic glycogen compared
      with control littermates, and were unable to normalize their blood glucose levels
      within 2 h after injection of insulin. The glucose intolerance of the L-PDK1-/-
      mice may be due to an inability of glucose to suppress hepatic glucose output
      through the gluconeogenic pathway, since the mRNA encoding hepatic PEPCK
      (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase) and SREBP1
      (sterol-regulatory-element-binding protein 1), which regulate gluconeogenesis,
      are no longer controlled by feeding. Furthermore, three other insulin-controlled
      genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2
      (insulin receptor substrate 2) and glucokinase, were regulated abnormally by
      feeding in the liver of PDK1-deficient mice. Finally, the L-PDK1-/- mice died
      between 4-16 weeks of age due to liver failure. These results establish that the
      PDK1 signalling pathway plays an important role in regulating glucose
      homoeostasis and controlling expression of insulin-regulated genes. They suggest
      that a deficiency of the PDK1 pathway in the liver could contribute to
      development of diabetes, as well as to liver failure.

PMID- 15554901
TI  - Tumour necrosis factor alpha (TNF)-TNF receptor 1-inducible cytoprotective
      proteins in the mouse liver: relevance of suppressors of cytokine signalling.
AB  - TNF (tumour necrosis factor alpha) induces tolerance towards itself in
      experimental liver injury. Tolerance induction has been shown to be dependent on
      TNFR1 (TNF receptor 1) signalling, but mechanisms and mediators of TNF-induced
      hepatic tolerance are unknown. We investigated the TNF-inducible gene-expression
      profile in livers of TNFR2-/- mice, using cDNA array technology. We found that,
      out of 793 investigated genes involved in inflammation, cell cycle and signal
      transduction, 282 were expressed in the mouse liver in response to TNF via TNFR1.
      Among those, expression of 78 genes was induced, while expression of 60 genes was
      reduced. We investigated further the cellular expression of the 27 most
      prominently induced genes, and found that 20 of these genes were up-regulated
      directly in parenchymal liver cells, representing potentially protective proteins
      and possible mediators of TNF tolerance. In vitro experiments revealed that
      overexpression of SOCS1 (silencer of cytokine signalling 1), a member of the SOCS
      family of proteins, as well as of HO-1 (haem oxygenase-1), but not of SOCS2 or
      SOCS3, protected isolated primary mouse hepatocytes from TNF-induced apoptosis.
      The identification of protective genes in hepatocytes is the prerequisite for
      future development of gene therapies for immune-mediated liver diseases.

PMID- 15554903
TI  - TraA and its N-terminal relaxase domain of the Gram-positive plasmid pIP501 show
      specific oriT binding and behave as dimers in solution.
AB  - TraA is the DNA relaxase encoded by the broad-host-range Grampositive plasmid
      pIP501. It is the second relaxase to be characterized from plasmids originating
      from Gram-positive organisms. Full-length TraA (654 amino acids) and the N
      terminal domain (246 amino acids), termed TraAN246, were expressed as 6xHis
      tagged fusions and purified. Small-angle X-ray scattering and chemical cross
      linking proved that TraAN246 and TraA form dimers in solution. Both proteins
      revealed oriTpIP501 (origin of transfer of pIP501) cleavage activity on
      supercoiled plasmid DNA in vitro. oriT binding was demonstrated by
      electrophoretic mobility shift assays. Radiolabelled oligonucleotides covering
      different parts of oriTpIP501 were subjected to binding with TraA and TraAN246.
      The KD of the protein-DNA complex encompassing the inverted repeat, the nick site
      and an additional 7 bases was found to be 55 nM for TraA and 26 nM for TraAN246.
      The unfolding of both protein constructs was monitored by measuring the change in
      the CD signal at 220 nm upon temperature change. The unfolding transition of both
      proteins occurred at approx. 42 degrees C. CD spectra measured at 20 degrees C
      showed 30% a-helix and 13% b-sheet for TraA, and 27% alpha-helix and 18% beta
      sheet content for the truncated protein. Upon DNA binding, an enhanced secondary
      structure content and increased thermal stability were observed for the TraAN246
      protein, suggesting an induced-fit mechanism for the formation of the specific
      relaxase-oriT complex.

PMID- 15554904
TI  - Sp3 is involved in the regulation of SOCS3 gene expression.
AB  - Cytokine-induced expression of SOCS (suppressor of cytokine signalling) molecules
      is important for the negative regulatory control of STAT (signal transduction and
      activators of transcription)-dependent cytokine signalling, e.g. for the signal
      transduction of IL-6 (interleukin-6)-type cytokines through the JAK (Janus
      kinase)/STAT cascade. STAT activation itself represents an important step in the
      transcriptional activation of SOCS3 gene expression. However, downstream of the
      STAT-responsive element, the SOCS3 gene contains a GC-rich element in its 5'
      upstream region. The aim of the present study was to investigate the implications
      of this GC-rich element in the transcriptional control of SOCS3 gene expression.
      In the present study, we show that mutation of this GC-rich element abolishes IL
      6-dependent transcriptional activation of the SOCS3 promoter and that Sp3
      (specificity protein 3), a ubiquitously expressed transcription factor, but not
      Sp1 binds to this GC-rich motif, suggesting that Sp3 is involved in the
      regulation of SOCS3 expression. The results suggest that Sp3 is important for IL
      6-induced transcriptional activation of the SOCS3 (gene) promoter and acts as an
      enhancer of basal as well as induced transcriptional activity, resulting in
      enhanced SOCS3 mRNA and protein expression. Mutation of Lys-483, a potential
      target for Sp3 acetylation, inhibited Sp3-mediated enhancement of SOCS3 mRNA
      expression and SOCS3 promoter activation, indicating that the acetylation of this
      lysine residue of Sp3 is important for the enhancing effect of Sp3 on SOCS3
      expression.

PMID- 15554905
TI  - Vascular gap junctions and implications for hypertension.
AB  - Four connexin (Cx) molecules, namely Cx37, Cx40, Cx43 and Cx45, are expressed in
      the gap junctions that exist within and between the cellular layers of arteries.
      Endothelial cells are well coupled by large gap junctions expressing Cx37, Cx40
      and, to a lesser extent, Cx43, whose expression may be more subject to regulation
      by physical factors. Smooth muscle cells are more heterogeneously coupled by gap
      junctions that are small and rare. The identity of the Cx expressed in the media
      may vary among different arteries. Myoendothelial gap junctions are small and
      more common in resistance arteries with fewer layers of smooth muscle cells.
      Given the small size of these gap junctions and the rapid turnover rate of Cxs,
      homocellular coupling in the media and heterocellular coupling between the cell
      layers may be subject to more dynamic control than coupling in the endothelium.
      Vascular gap junctions have been implicated in a number of vasomotor responses
      that may regulate vascular tone and blood pressure. These include the mechanism
      of action of the vasodilator, endothelium-derived hyperpolarizing factor (EDHF),
      the myogenic constriction to intramural pressure increase, the spontaneous or
      agonist-induced vasomotion of arteries and arterioles and the spreading
      vasodilation and constriction observed in microcirculatory networks. Few data are
      available on Cx expression in the media of resistance arteries during
      hypertension. Changes in the expression of Cx43 described in the media of the
      aorta of hypertensive rats vary with the hypertensive model studied and are
      likely to represent adaptations to structural changes in the vascular wall. In
      contrast, in the endothelium of the caudal and mesenteric arteries of
      spontaneously hypertensive rats, expression of Cxs is significantly decreased
      compared with arteries from normotensive rats and this decrease is reversed by
      inhibitors of the renin-angiotensin system. During hypertension, the activity of
      EDHF is decreased in the mesenteric artery, but this occurs much later than the
      initial increase in blood pressure and the decrease in endothelial Cxs,
      suggesting that changes in EDHF may not be causally related to hypertension or to
      the changes in endothelial Cxs. Upregulation of the myogenic response and the
      incidence of vasomotion has been reported in hypertension. Little is currently
      known of the effects of hypertension on spreading vasomotor responses. Deletion
      of specific Cxs in genetically modified mice is complicated by neonatal lethality
      or coordinate regulation and compensatory changes in the remaining Cxs.
      Nevertheless, mice in which Cx40 has been deleted are hypertensive and spreading
      vasodilatory responses are significantly impaired. Determination of a role for
      specific Cxs in the control of blood pressure must await the development of
      animals in which Cx expression can be modulated in a more complex temporal and
      tissue-specific manner.

PMID- 15554906
TI  - Oscillatory transient inward currents in ventricular myocytes of healthy versus
      myopathic Syrian hamster.
AB  - The present experiments were performed in order to study abnormal action
      potential configuration and ion channel activity in ventricular myocytes obtained
      from 23 male myopathic Syrian hamsters (Biobreeders strain 14.6, 32-52 weeks old)
      compared with 10 age-matched healthy control hamsters (Biobreeders F1B) by means
      of whole-cell patch-clamp techniques. The results show that the myopathic
      myocytes had a longer action potential duration, a reduced transient outward K(+)
      current on depolarization and a smaller transient inward current on
      repolarization after prolonged depolarizing pulses (> 500 msec). However, the L
      type Ca(2+) current and the inwardly rectifing K(+) current were not
      significantly different from those of healthy myocytes. The oscillatory transient
      inward currents could be diminished by treatment with ryanodine (0.01-1
      micromol/L), a sarcoplasmic reticulum (SR) Ca(2+) release channel blocker, or
      with Na(+)-free superfusate. We conclude that the hereditary myopathic hamsters
      are less likely to develop delayed after depolarization-related transient inward
      currents and triggered arrhythmias owing to a smaller SR Ca(2+) content.

PMID- 15554907
TI  - Application of liquid chromatography-mass spectrometry to monitoring plasma
      cyclophosphamide levels in phase I trial cancer patients.
AB  - A specific and efficient liquid chromatography-mass spectrometry (LC-MS) method
      was established for monitoring patient plasma cyclophosphamide levels in a phase
      I trial of an oral cyclophosphamide-based combination chemotherapy regimen. An
      Agilent 1100 Series LC-MSD system (Agilent Technologies, Avondale, PA, USA), with
      a single quadrupole mass detector using a positive atmospheric pressure chemical
      ionization (APCI) interface and single ion monitoring at m/z 261, was used.
      Chromatography was performed using a LUNA C8 5 microm 30 x 4.6 mm stainless steel
      column (Phenomenex, Torrance, CA, USA) and a mobile phase of aqueous acetonitrile
      pumped at a flow rate of 0.7 mL/min. High-throughput solid-phase sample
      extraction was performed using a Gilson ASPEC XL4 system (Gilson Medical,
      Middleton, WI, USA) controlled by prestored programs. The standard curve for
      cyclophosphamide was linear over the concentration range 0.026-1.08 microg/mL
      (r(2) > 0.994). Intra- and interassay accuracy and precision were 97-107 and 3
      10%, respectively. The limit of detection was determined to be 0.01 microg/mL.
      Single ion monitoring at m/z 261 provided a high degree of specificity without
      interference from the matrix or other chemotherapy drugs. Automated sample
      processing allowed the analysis of a large number of plasma samples from a
      clinical trial of repeated daily oral dosing of cyclophosphamide. One hour after
      dosing, cyclophosphamide was detected in 98 of 106 plasma specimens at
      concentrations ranging between 0.03 and 4.88 microg/mL. Twenty-four hours after
      dosing, cyclophosphamide was detected in 72 of 77 plasma specimens at
      concentrations ranging between 0.06 and 3.13 microg/mL. There were no time
      dependent changes in cyclophosphamide concentration during the 43 day period of
      repeated daily oral dosing. There was no correlation between cyclophosphamide
      dose and plasma concentration, despite the wide range of doses given in the
      clinical trial (50-125 mg/m(2)). We conclude that a solid-phase extraction LC-MS
      technique was validated for determining cyclophosphamide in human plasma.
      Interoccasion variability in the rate of oral absorption and in the clearance of
      systemically available drug may have contributed to the wide range of
      cyclophosphamide concentrations found at 1 and 24 h after tablet ingestion.

PMID- 15554909
TI  - Effects of antidigoxin antiserum on endoxin levels, apoptosis and the expression
      of Bax and Bcl-2 protein in ischaemia-reperfusion myocardium.
AB  - The aim of the present study was to investigate the effects of antidigoxin
      antiserum (ADA), an endoxin special antagonist, on endoxin levels, apoptosis and
      the expression of the apoptosis-related protein bcl-2 and bax in myocardial
      ischaemia-reperfusion (MIR). The left anterior descending coronary artery was
      subjected to 30 min ischaemia followed by 45 min reperfusion in open-chest
      anaesthetized rats. The rats were divided randomly into seven groups: a sham
      operated group, an MIR group, a vehicle control (normal saline) group, and groups
      receiving verapamil (5 mg/kg) or ADA (9, 18 and 36 mg/kg). The drugs were
      injected into rats via the femoral vein before reperfusion was commenced.
      Myocardial endoxin levels were measured by radioimmunoassay. Apoptotic cells was
      detected using the terminal deoxyribonucleotidyl transferase-mediated dUTP
      digoxigenin nick end-labeling method. The expression of the apoptosis-related
      proteins bcl-2 and bax was detected by immunohistochemistry and their
      semiquantification scores were recorded by a computer image analysis system.
      Myocardial endoxin levels, the number of apoptotic cells and bax protein
      expression were increased in the MIR group compared with the sham group. Although
      bcl-2 protein expression was elevated in the MIR group, there was no significant
      difference between the MIR and sham groups. However, the ratio of bcl-2/bax was
      significantly decreased in the MIR group. In the group receiving 36 mg/kg ADA,
      myocardial endoxin levels, the number of apoptotic cells and bax protein
      expression were significantly decreased; bcl-2 protein expression was enhanced.
      The bcl-2/bax ratio was increased. The results suggest that ADA inhibited
      myocardial apoptosis induced by MIR in rats. The mechanisms involved require
      further investigation, but the present study may suggest that ADA prevents bax
      upregulation and enhances bcl-2 upregulation by antagonizing the effects of
      endoxin.

PMID- 15554908
TI  - Changes in renal haemodynamics induced by indomethacin in the rat involve
      cytochrome P450 arachidonic acid-dependent epoxygenases.
AB  - A significant renal vasodilation was observed previously after an acute cyclo
      oxygenase (COX) inhibition induced with indomethacin. Because this effect could
      be due to COX-dependent intrarenal metabolization of arachidonic acid through
      cytochrome P450 (CYP450) pathways, the aim of the present study was to
      investigate, in vivo, possible interactions between COX and CYP450 mono
      oxygenases. Mean arterial pressure (MAP) and renal blood flow (RBF), using an
      electromagnetic flow transducer for RBF evaluation, were measured continuously in
      71 anaesthetized euvolaemic rats. Appropriate solvents (vehicle), 3 mg/kg
      indomethacin, 17-octadecynoic acid (17-ODYA; 2 mmol/L), either miconazole (MI;
      1.5 mmol/L) or N-methylsulphonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH; 5
      mg/kg) and N'-hydroxyphenylformamidine (HET0016; 5 or 10 mg/kg) were administered
      to inhibit either COX, CYP450 mono-oxygenases, epoxygenases or hydroxylase,
      respectively. The CYP450 and COX inhibitors were also combined as follows: 17
      ODYA/indomethacin, MI (or MS-PPOH)/indomethacin, HET0016/indomethacin and
      indomethacin/HET0016. Mean arterial pressure and RBF were not modified by
      vehicle, 17-ODYA or MI (or MS-PPOH). However, MAP decreased slightly (P < 0.05;
      paired t-test, 5 d.f.) and RBF increased transiently (P < 0.05; anova, 5 d.f.)
      after HET0016. In contrast, MAP decreased by 10 mmHg (P < 0.05) and RBF increased
      by 10% (P < 0.05) after indomethacin. This enhancement was prevented by 17-ODYA
      or MI (or MS-PPOH), but not by HET0016. Moreover, RBF increased step-wise to 21%
      in the indomethacin/HET0016 experiment (P < 0.05). Consequently, changes from
      baseline in renal vascular resistance differed among treatments, averaging -2 +/-
      3 (vehicle), -13 +/- 3 (indomethacin; P < 0.05 vs vehicle), -4 +/- 3 (17
      ODYA/indomethacin), -3 +/- 4 (MI or MS-PPOH/indomethacin), -15 +/- 3
      (HET0016/indomethacin; P < 0.05) and -22 +/- 4% (indomethacin/HET0016; P < 0.05).
      In conclusion, these results demonstrate that the renal vasodilation induced by
      indomethacin can be prevented by prior inhibition of CYP450 mono-oxygenases and
      further suggest that the CYP450 epoxygenases pathway may prevail.

PMID- 15554910
TI  - High-salt diet and responses of the pressurized mesenteric artery of the dog to
      noradrenaline and acetylcholine.
AB  - A high-salt diet in rats has been shown to result in enhanced vasoconstrictor
      and/or reduced vasodilator responses of isolated arteries to agonists. The
      present experiments were designed to investigate the effects of dietary salt on
      the responses of the pressurized mesenteric resistance artery of the dog to
      constrictor and dilator agents. Dogs were fed diets containing three different
      levels of salt with sodium concentrations (in mmol/kg per day) of 0.4 (low salt;
      LS), 3.0 (intermediate salt; IS) and 6.0 (high salt; HS) for a period of 4 weeks.
      At the end of the feeding period, animals were killed and lengths of third-order
      mesenteric artery were obtained and mounted in a perfusion myograph and changes
      in internal diameter were measured using a microscope and video-tracking device.
      The responses to noradrenaline (NA), acetylcholine (ACh) and sodium nitroprusside
      (SNP) were then determined. The vasoconstrictor responses to NA were identical in
      the three groups. However, the relaxation response of the vessels to ACh was
      attenuated in HS dogs compared with LS dogs (P < 0.05), but not with IS dogs. The
      application of N(G)-nitro-l-arginine methyl ester, an inhibitor of nitric oxide
      synthase, reduced the relaxation responses to ACh comparably in all three groups.
      The relaxation responses of the vessels to SNP were similar in all groups. These
      results indicate that, in the dog mesenteric resistance artery, a high-salt diet
      does not affect vasoconstrictor responses to NA, but does attenuate the
      vasorelaxant action of ACh, largely by inhibiting the production of endothelium
      derived relaxing factor.

PMID- 15554911
TI  - Improvement of spatial cognition with dietary docosahexaenoic acid is associated
      with an increase in Fos expression in rat CA1 hippocampus.
AB  - Twenty 5-week-old male Wistar rats were divided into two groups: one group was
      fed a fish oil-deficient diet and the other group was fed the same diet
      supplemented with per orally administered docosahexaenoic acid (DHA) for 12
      weeks. Six weeks after the start of the administration of DHA, rats were trained
      for 6 weeks to acquire a reward at the end of each of four arms of an eight-arm
      radial maze. On completion of the radial maze task, the Fos expression in the
      hippocampus was examined immunohistochemically. Chronic DHA administration
      significantly reduced the number of reference and working memory errors. The
      number of Fos-positive neurons in the CA1 hippocampus significantly increased in
      DHA-treated rats compared with control rats, demonstrating a statistically
      significant negative correlation with the number of reference memory errors.
      These results suggest that the DHA-induced improvement in spatial cognition is
      associated with increased Fos expression in the CA1 hippocampus.

PMID- 15554912
TI  - Differences in the determinants of eplerenone, spironolactone and aldosterone
      binding to the mineralocorticoid receptor.
AB  - The importance of mineralocorticoid receptor (MR) antagonists in the treatment of
      cardiovascular disease has been emphasised by two recent clinical trials, one
      using spironolactone and the other using a new selective MR antagonist, namely
      eplerenone. Eplerenone has a very low affinity for the glucocorticoid receptor
      (GR). Determinants of binding specificity of eplerenone to the MR were
      investigated using chimeras created between the ligand-binding domains (LBD) of
      the MR and the GR. These chimeras had been used previously to investigate
      aldosterone and spironolactone binding specificity to the MR. Eplerenone competed
      strongly for [(3)H]-dexamethasone binding to a MR/GR chimera containing amino
      acids 804-874 of the MR and weakly to a chimera containing amino acids 672-803 of
      the MR. Within the 804-874 region, eplerenone competed for [(3)H]-dexamethasone
      binding to a chimera containing amino acids 820-844 of the MR, although the
      calculated affinity was approximately 10-fold lower than for binding to the full
      length MR LBD. Similar results were obtained using another MR antagonist, namely
      spironolactone. Modelling of eplerenone binding to the MR LBD, based on the GR
      LBD crystal structure, suggests that amino acids 820-844 affect the overall shape
      of the ligand-binding pocket and that eplerenone acts as an MR antagonist because
      it fails to stabilize the active conformation of the receptor. In contrast with
      results with the MR antagonists eplerenone and spironolactone, amino acids 820
      844 are sufficient in themselves to confer high-affinity aldosterone binding to
      the MR, suggesting that the binding determinants of the two antagonists are
      similar to each other but differ from those of aldosterone.

PMID- 15554913
TI  - Mechanism of ouabain-induced contractions in guinea-pig tracheal rings.
AB  - The aim of the present study was to analyse the mechanism that underlies the
      force development induced by ouabain (ED(100) = 100 micromol/L) in guinea-pig
      tracheal rings. The dose-response curve showed that concentrations of ouabain
      above 100 micromol/L evoked smaller contractions. Ouabain, at 100 micromol/L,
      produced two long-lasting consecutive transient contractions. The peak of the
      first contraction was 750 +/- 75 mg, whereas the peak of the second contraction
      was 280 +/- 46 mg. Both contractions induced by ouabain were dependent on
      extracellular Ca(2+). Consistent with this, verapamil (10 micromol/L) inhibited
      the first and second contractions by 77 and 59%, respectively. 3,4
      Dichlorobenzamil (20 micromol/L) inhibited the first and second contractions by
      68 and 97%, respectively. Simultaneous exposure to 15 mmol/L sodium solution and
      100 micromol/L ouabain evoked only one transient contraction, larger (987 +/- 135
      mg) than either of the ouabain-induced contractions. Inhibition of the
      sarcoendoplasmic reticulum Ca-ATPase with cyclopiazonic acid potentiated the
      first and second ouabain-induced contractions by 47 and 300%, respectively.
      Atropine (1 micromol/L) inhibited the first and second contractions by 44 and
      76%, respectively. In conclusion, the results of the present study are relevant
      to the understanding of the mechanisms by which ouabain (100 micromol/L)
      contracts guinea-pig tracheal rings. At the muscular level, oubain induces Ca(2+)
      influx through L-type Ca(2+) channels and the reverse mode of the sodium-calcium
      exchanger. At the nerve terminals, ouabain promotes the release of acetylcholine
      secondary to the increase in Ca(2+) influx mediated by the reverse mode of the
      sodium-calcium exchanger.

PMID- 15554914
TI  - Upregulation of Fas/Fas ligand-mediated apoptosis by gossypol in an immortalized
      human alveolar lung cancer cell line.
AB  - Gossypol has wide antineoplastic effects in vitro, but its effects on human lung
      cancer have not been explored. To evaluate the activity of gossypol against
      alveolar cell lung cancer and to provide information on the mechanism of action,
      we examined the effects of gossypol on the proliferation of A549 cells indirectly
      using an XTT assay and on the distribution of cells within the phases of the cell
      cycle using flow cytometry. We also examined several factors that may affect
      apoptosis, including p53, p21/WAF1, Fas receptor, Fas ligand (FasL) and caspase 8
      activity. The results showed that gossypol inhibited proliferation of A549 cells
      at a concentration of 0.5 micromol/L after 12 h treatment. The effect was both
      dose- and time-dependent by the induction of apoptosis without the effect of p53
      and p21/WAF1. Upregulation of Fas/FasL, in association with the activation of
      downstream caspase 8 activity, was observed following treatment with gossypol.
      The Fas/FasL pathway accounted for 75% of gossypol-mediated apoptosis. We suggest
      that the Fas/FasL apoptotic system is the major pathway for gossypol-mediated
      apoptosis of A549 cells. Gossypol had no effect on the distribution of A549 cells
      within the phases of the cell cycle. In conclusion, gossypol inhibited A549 cells
      mainly by induction of the Fas/FasL apoptotic pathway, but not the p53 and
      p21/WAF1 pathway.

PMID- 15554915
TI  - Role of endogenous macrophage inflammatory protein-2 in regulating fever induced
      by bacterial endotoxin in normal and immunosuppressed rats.
AB  - During myelosuppressive chemotherapy, Gram-negative bacterial infection with
      consequent exposure to lipopolysaccharide (LPS) is one of the most important
      causes of persistent fever. The classical model of the pathogenesis of fever
      suggests that pro-inflammatory cytokines, produced by leucocytes in the
      bloodstream in response to exogenous pyrogens such as bacterial LPS, represent
      the distal mediators of the febrile response. Neutrophils are the first effectors
      cells and the most prominent leucocyte population involved in acute bacterial
      infection. Macrophage inflammatory protein (MIP)-2 plays a crucial role in
      influencing early cell trafficking and neutrophil activation during
      pathophysiological processes and serves the same chemotactic function as human
      interleukin-8. In the present study, we investigated the role of MIP-2 in the
      development of a febrile response induced by LPS in immunocompetent and
      leukopenic rats. Intraperitoneal injection of LPS in leukopenic rats elicited a
      biphasic febrile response of rapid onset, the magnitude and duration of which
      were significantly greater than in immunocompetent animals. The febrile responses
      to LPS were accompanied by a pronounced induction of serum MIP-2 levels at 1, 2
      and 4 h compared with their respective controls. In both normal and leukopenic
      rats, neutralization of endogenous MIP-2 bioactivity by systemic administration
      of antirat MIP-2 antibody caused a significant attenuation of the early phase of
      LPS fever. However, in contrast with normal rats, the second phase of fever was
      unimpaired by anti-MIP-2 in leukopenic rats. These findings suggest that
      circulating MIP-2 is involved in the generation of the early phase of LPS fever
      that contributes to the maintenance of the later phase of fever in
      immunocompetent, but not leukopenic, rats. Our data support a regulatory role for
      endogenous MIP-2 in initiating the fever responses to LPS. Furthermore, these
      results provide evidence that different cellular and humoral mechanisms are
      implicated in the development of a febrile response triggered by Gram-negative
      bacterial infections in leukopenic hosts.

PMID- 15554917
TI  - Inhibition of l-arginine transport in platelets by asymmetric dimethylarginine
      and N-monomethyl-l-arginine: effects of arterial hypertension.
AB  - Nitric oxide (NO) produced by human platelets plays an important role in all
      stages of platelet activation. l-Arginine, the precursor for NO synthesis,
      modulates NO production by platelets. The l-arginine analogues asymmetric
      dimethylarginine (ADMA) and N(G)-monomethyl-l-arginine (l-NMMA) are endogenous
      inhibitors of nitric oxide synthase (NOS), involved in the physiopathology of
      arterial hypertension. The aim of the present study was to investigate the
      inhibitory effects of endogenous and exogenous l-arginine analogues on l-arginine
      influx in platelets from healthy controls and hypertensive patients. Twelve
      patients with uncomplicated essential hypertension (stage I) and 15 age-matched
      normotensive controls participated in the present study. Platelets were isolated
      and incubated with l-[(3)H]-arginine and increasing concentrations of l-arginine
      analogues (5-2000 micromol/L). The influx of l-arginine was inhibited in a
      concentration-dependent manner by l-NMMA in platelets from controls (K(i) = 42 +/
      6 micromol/L) and this inhibitory effect was markedly higher in hypertensive
      platelets (K(i) = 23 +/- 4 micromol/L). Similarly, the K(i) for ADMA inhibition
      of l-arginine transport was significantly more pronounced in platelets from
      hypertensive patients (K(i) = 16 +/- 1 micromol/L) compared with controls (K(i) =
      27 +/- 2 micromol/L). In contrast, N(G)-nitro-l-arginine methyl ester (l-NAME)
      was found to be a weak inhibitor of l-arginine influx in platelets from controls
      (K(i) = 1917 +/- 319 micromol/L) and hypertensive patients (K(i) = 2279 +/- 578
      micromol/L). Aminoguanidine, a selective inhibitor of inducible NOS, failed to
      inhibit l-arginine transport. Our findings provide the first evidence that ADMA
      and l-NMMA markedly inhibit l-arginine transport in human platelets, an effect
      that is more pronounced in hypertensive patients. It is possible that endogenous
      l-arginine analogues, by inhibiting NO synthesis, are involved in the platelet
      activation present in hypertension.

PMID- 15554916
TI  - Effect of calmidazolium on Ca(+2) movement and proliferation in human
      osteosarcoma cells.
AB  - In human MG63 osteosarcoma cells, the effect of calmidazolium on [Ca(2+)](i) and
      proliferation was explored using fura-2 and ELISA, respectively. Calmidazolium,
      at concentrations greater than 0.1 micromol/L, caused a rapid increase in
      [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 0.5 micromol/L). The
      calmidazolium-induced [Ca(2+)](i) increase was reduced by 66% by removal of
      extracellular Ca(2+). In Ca(2+)-free medium, thapsigargin, an inhibitor of the
      endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic increase in [Ca(2+)](i),
      after which the effect of calmidazolium to increase [Ca(2+)](i) was completely
      inhibited. U73122, an inhibitor of phospholipase C (PLC), abolished histamine
      (but not calmidazolium)-induced increases in [Ca(2+)](i). Pretreatment with
      phorbol 12-myristate 13-acetate to activate protein kinase C inhibited the
      calmidazolium-induced increase in [Ca(2+)](i) in Ca(2+)-containing medium by 47%.
      Separately, it was found that overnight treatment with 2-10 micromol/L
      calmidazolium inhibited cell proliferation in a concentration-dependent manner.
      These results suggest that calmidazolium increases [Ca(2+)](i) by stimulating
      extracellular Ca(2+) influx and also by causing release of intracellular Ca(2+)
      from the endoplasmic reticulum in a PLC-independent manner. Calmidazolium may be
      cytotoxic to osteosarcoma cells.

PMID- 15554918
TI  - Negative chronotropic response to adenosine receptor stimulation in rat right
      atria after run training.
AB  - The aim of the present study was to evaluate the potency and maximal responses
      (E(max)) to the adenosine receptor agonists N(6)-cyclopentyladenosine (CPA), N
      ethylcarboxamidoadenosine (NECA) and N(6)-(3-iodobenzyl)-5'-N
      methylcarbaxamidoadenosine (IB-MECA) in right atria from trained rats. We also
      investigated the interaction between the training bradycardia and the sensitivity
      of the chronotropic response mediated by adenosine receptor stimulation. Animals
      were submitted to run training for 60 min, 5 days a week, over a period of 8
      weeks. Mean blood pressure and heart rate were measured in conscious animals.
      Right atria were isolated and concentration-response curves to CPA, NECA and IB
      MECA were obtained. A reduction in heart rate was found in trained rats,
      indicating that the training programme was successful in inducing physical
      conditioning. The three adenosine receptor agonists induced a concentration
      dependent negative chronotropic response. The rank order of potency and E(max)
      for the three adenosine receptor agonists was CPA > NECA > IB-MECA. Dynamic
      exercise for 8 weeks did not alter the E(max) for CPA, NECA and IB-MECA.
      Similarly, the potencies of CPA and NECA were not affected by run training,
      whereas the potency of IB-MECA was reduced (6.10 +/- 0.09 vs 5.66 +/- 0.10 for
      sedentary and trained groups, respectively). In conclusion, run training for 8
      weeks induced a desensitization of the chronotropic response to IB-MECA without
      changing the potency of CPA and NECA. These findings exclude the participation of
      adenosine receptors in the training bradycardia.

PMID- 15554920
TI  - Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved
      puzzle.
AB  - In recent years, nitric oxide (NO), a gas previously considered to be a
      potentially toxic chemical, has been established as a diffusible universal
      messenger that mediates cell-cell communication throughout the body. Constitutive
      and inducible NO production regulate numerous essential functions of the
      gastrointestinal mucosa, such as maintenance of adequate perfusion, regulation of
      microvascular and epithelial permeability, and regulation of the immune response.
      Up-regulation of the production of NO via expression of inducible nitric oxide
      synthase (iNOS) represents part of a prompt intestinal antibacterial response;
      however, NO has also been associated with the initiation and maintenance of
      inflammation in human inflammatory bowel disease (IBD). Recent studies on animal
      models of experimental IBD have shown that constitutive and inducible NO
      production seems to be beneficial during acute colitis, but sustained up
      regulation of NO is detrimental. This fact is also supported by studies on mice
      genetically deficient in various NOS isoforms. However, the mechanism by which NO
      proceeds from being an indispensable homeostatic regulator to a harmful
      destructor remains unknown. Furthermore, extrapolation of data from animal
      colitis models to human IBD is questionable. The purpose of this review is to
      update our knowledge about the role of this universal mediator and the enzymes
      that generate it in the pathogenesis of IBD.

PMID- 15554919
TI  - Regulation of T-cell receptor signalling by membrane microdomains.
AB  - There is now considerable evidence suggesting that the plasma membrane of
      mammalian cells is compartmentalized by functional lipid raft microdomains. These
      structures are assemblies of specialized lipids and proteins and have been
      implicated in diverse biological functions. Analysis of their protein content
      using proteomics and other methods revealed enrichment of signalling proteins,
      suggesting a role for these domains in intracellular signalling. In T
      lymphocytes, structure/function experiments and complementary pharmacological
      studies have shown that raft microdomains control the localization and function
      of proteins which are components of signalling pathways regulated by the T-cell
      antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation
      in lipid rafts is presented. However, despite substantial progress in the field,
      critical questions remain. For example, it is unclear if membrane rafts represent
      a homogeneous population and if their structure is modified upon TCR stimulation.
      In the future, proteomics and the parallel development of complementary
      analytical methods will undoubtedly contribute in further delineating the role of
      lipid rafts in signal transduction mechanisms.

PMID- 15554921
TI  - Parasitic helminths tip the balance: potential anti-inflammatory therapies.

PMID- 15554922
TI  - Epitope-specific crosslinking of CD45 down-regulates membrane-associated tyrosine
      phosphatase activity and triggers early signalling events in human activated T
      cells.
AB  - CD45 engagement by monoclonal antibodies on human activated T cells triggers
      tumour necrosis factor-alpha (TNF-alpha) gene transcription in an epitope
      specific manner. To dissect the early signalling events leading to TNF-alpha gene
      expression, we established that CD45 crosslinking resulted in tyrosine
      phosphorylation of p56lck, ZAP-70, CD3-zeta, LAT and Vav. This was accompanied by
      down-regulation of membrane-associated protein tyrosine phosphatase activity in
      the absence of demonstration of enhanced p56lck, p72syk and ZAP-70 kinase
      activity, which remained constitutive. These early events eventually triggered an
      intracellular Ca(2+) rise and phosphoinositide turnover. We conclude that down
      regulation of membrane-associated tyrosine phosphatase activity by CD45
      extracytoplasmic domain multimerization led, in an epitope-specific fashion, to
      unopposed tyrosine kinase activity and to the activation of the T-cell
      receptor/CD3 complex signalling cascade, resulting in TNF-alpha gene expression.
      This model strongly suggests that CD45 extracytoplasmic tail multimerization may
      contribute to the modulation T-cell functions.

PMID- 15554923
TI  - T cell receptor induced intracellular redistribution of type I protein kinase A.
AB  - The productive activation of CD4(+) T lymphocytes, leading to proliferation and
      cytokine secretion, requires precise temporal regulation of intracellular cyclic
      AMP concentrations. The major effector molecule activated by cyclic AMP in
      mammalian cells is the cyclic AMP-dependent protein kinase A (PKA). The type I
      PKA isozyme mediates the inhibitory effects of cyclic AMP on T-cell activation.
      Using laser scanning confocal microscopy, we demonstrated that the regulation of
      PKA type I activity involves spatial redistribution of PKA type I molecules
      following T-cell receptor (TCR) stimulation. In resting T cells, PKA type I was
      located in membrane proximal regions and distributed equally across the cell.
      Shortly after antigen engagement, T cells and antigen-presenting cells formed an
      area of intense contact, known as the immunological synapse. TCR concentrated at
      the synapse, whereas PKA type I molecules redistributed to the opposite cell pole
      within 10 min after T-cell stimulation. Type I PKA redistribution was solely
      dependent on TCR signalling, because we observed the same temporal and spatial
      distribution after antibody-mediated cross-linking of the TCR-associated CD3
      complex. Segregation of TCR and PKA type I molecules was maintained for at least
      20 min. Thirty minutes after stimulation, PKA type I partially colocalized with
      the TCR. After 60 min, PKA type I distribution again approached the resting
      state. Considering that initial TCR signals lead to increases in intracellular
      cyclic AMP, PKA type I molecules may be targeted towards localized cyclic AMP
      accumulations or transported away from these areas, depending on the requirements
      of the cellular response.

PMID- 15554924
TI  - Major histocompatibility complex class I-intercellular adhesion molecule-1
      association on the surface of target cells: implications for antigen presentation
      to cytotoxic T lymphocytes.
AB  - Polarization and segregation of the T-cell receptor (TCR) and integrins upon
      productive cytotoxic T-lymphocyte (CTL) target cell encounters are well
      documented. Much less is known about the redistribution of major
      histocompatibility complex class I (MHC-I) and intercellular adhesion molecule-1
      (ICAM-1) proteins on target cells interacting with CTLs. Here we show that human
      leucocyte antigen-A2 (HLA-A2) MHC-I and ICAM-1 are physically associated and
      recovered from both the raft fraction and the fraction of soluble membranes of
      target cells. Conjugation of target cells with surrogate CTLs, i.e. polystyrene
      beads loaded with antibodies specific for HLA-A2 and ICAM-1, induced the
      accumulation of membrane rafts, and beads loaded with ICAM-1-specific antibodies
      caused the selective recruitment of HLA-A2 MHC-I at the contact area of the
      target cells. Disruption of raft integrity on target cells led to a release of
      HLA-A2 and ICAM-1 from the raft fraction, abatement of HLA-A2 polarization, and
      diminished the ability of target cells bearing viral peptides to induce a Ca(2+)
      flux in virus-specific CTLs. These data suggest that productive engagement of
      ICAM-1 on target cells facilitates the polarization of MHC-I at the CTL-target
      cell interface, augmenting presentation of cognate peptide-MHC (pMHC) complexes
      to CTLs. We propose that ICAM-1-MHC-I association on the cell membrane is a
      mechanism that enhances the linkage between antigen recognition and early
      immunological synapse formation.

PMID- 15554925
TI  - Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized
      human monocyte-derived dendritic cells.
AB  - Dendritic cells (DC) play critical roles in generating an immune response and in
      inducing tolerance. Diverse microenvironmental factors can 'polarize' DC toward
      an immunogenic or non-immunogenic phenotype. Among the various microenvironmental
      factors, interleukin-10 (IL-10) exhibits a potent immunosuppressive effect on
      antigen-presenting cells (APC). Here, we show that monocyte-derived DC generated
      in the presence of IL-10 exhibit a profound down-regulation of many genes that
      are associated with immune activation and show that the IL-10-grown DC are poor
      stimulators of CD8(+) T cells in a strictly autologous and major
      histocompatibility complex (MHC) class I-restricted melanoma antigen recognized
      by T cells (MART-1) epitope presentation system. However, these IL-10-grown DC
      can efficiently activate the epitope-specific CD8(+) T cells when they are made
      to present the epitope following transduction with an adenoviral vector
      expressing the MART-1 antigen. In addition, we show that the MART-1 protein
      colocalizes with the MHC class I protein, equally well, in the iDC and in the DC
      cultured in presence of IL-10 when both DC types are infected with the viral
      vector. We also show that the vector transduced DC present the MART-1(27-35)
      epitope for a sustained period compared to the peptide pulsed DC. These data
      suggest that although DCs generated in the presence of IL-10 tend to be non
      immunogenic, they are capable of processing and presenting an antigen when the
      antigen is synthesized within the DC.

PMID- 15554926
TI  - Site-specific regulation of tissue dendritic cell function by granulocyte
      macrophage colony-stimulating-factor.
AB  - Tissue dendritic cells (DC) are usually associated with phagocytic function but
      poor T-cell immunostimulatory capacity. Following activation, dendritic cells are
      stimulated to leave tissue sites and migrate to lymphoid tissue, acquiring
      immunostimulatory capacity during the process. We provide evidence that the
      immunostimulatory capacity of tissue DC, but not spleen cells, can be affected in
      situ by granulocyte-macrophage colony-stimulating-factor (GM-CSF). Initially it
      was found that islet cells from non-obese diabetic and BALB/c mice, which produce
      GM-CSF, showed significantly higher immunostimulatory capacity than islets from
      C3H and C57BL/6 mice, which do not produce GM-CSF. Second, pretreatment of
      nonobese diabetic mice with anti-GM-CSF antibody significantly reduced the
      immunostimulatory capacity of islet cells, but not spleen cells, although it had
      no effect on the numbers of cells expressing DC-associated antigens. Therefore
      the immunostimulatory function of islet DC is partially dependent on GM-CSF. By
      contrast, spleen DC immunostimulatory function does not show the same dependence
      on GM-CSF. This may affect the ability of dendritic cells to stimulate autoimmune
      responses or tolerance.

PMID- 15554927
TI  - In vivo exposure of murine dendritic cell and macrophage bone marrow progenitors
      to the phosphorylcholine-containing filarial nematode glycoprotein ES-62
      polarizes their differentiation to an anti-inflammatory phenotype.
AB  - We have previously shown in an in vitro study that the filarial nematode
      phosphorylcholine (PC)-containing glycoprotein ES-62 promotes a murine dendritic
      cell (DC) phenotype that induces T helper type 2 (Th2) responses. We now show
      that, in addition to directly priming Th2 responses, ES-62 can act to dampen down
      the pro-inflammatory DC responses elicited by lipopolysaccharide. Furthermore, we
      also demonstrate that murine DCs and macrophages derived ex vivo from bone marrow
      cells exposed in vivo to ES-62 by release from osmotic pumps are hyporesponsive
      to subsequent stimulation with lipopolysaccharide. These effects can be largely
      mimicked by exposure to the PC moiety of ES-62 conjugated to an irrelevant
      protein. The data we provide are, as far as we aware, the first to show that a
      defined pathogen product can modulate the developmental pathway of bone marrow
      cells of the immune system in vivo. Such a finding could have important
      implications for the use of pathogen products or their derivatives for
      immunotherapy.

PMID- 15554928
TI  - Characterization of T-regulatory cells, induced by immature dendritic cells,
      which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro
      and in vivo.
AB  - Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4(+) T
      cells and immature dendritic cells (DC), suppress enteroantigen-induced
      proliferation of CD4(+) CD25(-) T cells. The DC-induced Treg cells are a mixture
      of CD25(+) (10-20%) and CD25(-) (80-90%) T cells. However, all the suppressor
      activity in vitro and in vivo resides in the CD25(+) T-cell subset. The CD25(+)
      DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro
      through a transwell membrane, and their function does not appear to depend on
      previous activation. DC-induced CD25(+) Treg cells display a naive phenotype,
      expressing high levels of CD45RB and l-selectin (CD62L). In addition, the DC
      induced Treg cells mediate a stronger suppressive activity than prototype CD25(+)
      regulatory T cells. The DC-induced Treg cells, and hereof purified CD25(+) and
      CD25(-) T-cell fractions, were co-injected into severe combined immunodeficiency
      (SCID) mice with colitis-inducing CD4(+) CD25(-) T cells. Both unfractionated
      CD4(+) and purified CD25(+) Treg cells fully protected the recipients against the
      development of colitis. In contrast, co-transfer of fractionated CD25(-) T cells
      offered no protection against disease development. Enterobacterial antigen
      exposed CD4(+) T cells of the protected mice secreted higher levels of
      interleukin-10 and lower levels of interferon-gamma than the unprotected mice.
      The present data demonstrate DC-induced CD4(+) CD25(+) Treg cells, which
      phenotypically and functionally differ from the generally accepted prototype of
      CD25(+) Treg cells. These data may initiate new procedures for the expansion of
      Treg cells for clinical use.

PMID- 15554929
TI  - Activator protein-1 signalling pathway and apoptosis are modulated by poly(ADP
      ribose) polymerase-1 in experimental colitis.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA injury in
      the nucleus of eukaryotic cells and has been implicated in intestinal barrier
      dysfunction during inflammatory bowel diseases. In this study we investigated
      whether PARP-1 may regulate the inflammatory response of experimental colitis at
      the level of signal transduction mechanisms. Mice genetically deficient of PARP-1
      (PARP-1(-/-)) and wild-type littermates were subjected to rectal instillation of
      trinitrobenzene sulphonic acid (TNBS). Signs of inflammation were monitored for
      14 days. In wild-type mice, TNBS treatment resulted in colonic ulceration and
      marked apoptosis, which was associated with decreased colon content of the
      antiapoptotic protein Bcl-2, whereas the proapoptotic Bax was unchanged. Elevated
      levels of plasma nitrate/nitrite, metabolites of nitric oxide (NO), were also
      found. These inflammatory events were associated with activation of c-Jun-NH(2)
      terminal kinase (JNK), phosphorylation of c-Jun and activation of the nuclear
      transcription factor activator protein-1 (AP-1) in the colon. In contrast, PARP
      1(-/-) mice exhibited a significant reduction of colon damage and apoptosis,
      which was associated with increased colonic expression of Bcl-2 and lower levels
      of plasma nitrate/nitrite when compared to wild-type mice. Amelioration of colon
      damage was associated with a significant reduction of the activation of JNK and
      reduction of the DNA binding of AP-1. The data indicate that PARP-1 exerts a
      pathological role in colitis possibly by regulating the early stress-related
      transcriptional response through a positive modulation of the AP-1 and JNK
      pathways.

PMID- 15554930
TI  - Complement component C7 deficiency in two Spanish families.
AB  - Different genetic mutations have been described in complement component C7
      deficiency, a molecular defect clinically associated with an increased
      susceptibility to neisserial recurrent infections. In this work we report the
      genetic basis of C7 deficiency in two different Spanish families (family 1 and
      family 2). In family 1, of Gypsy ethnical background, exon-specific polymerase
      chain reaction and sequencing revealed a not previously described single base
      deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father,
      leading to a stop codon that causes the premature truncation of the C7 protein
      (K416 X 419). Additionally, the patient and her mother displayed a missense
      mutation at position 1135 (exon 9) located in the first nucleotide of the codon
      GGG (CGG), resulting in a change of amino acid (G357R). This mutation was firstly
      described in individuals of Moroccan Sephardic Jewish ancestry and has been also
      reported among Spaniards. In family 2, another novel mutation was found in
      homozygosity in two siblings; a two base-pair deletion of nucleotides 1922 and
      1923 in exon 14 leading to the generation of a downstream stop codon causing the
      truncation of the C7 protein product (S620 X 630). Our results provide more
      evidence for the heterogeneous molecular basis of C7 deficiency as well as for
      the subsequent susceptibility to meningococcal disease, since different families
      carry different molecular defects. On the other hand, certain C7 defects appear
      to be prevalent in individuals from certain populations or living in defined
      geographical areas.

PMID- 15554932
TI  - Institutional review board approval for clinical application of new medical
      devices rather than government agency.

PMID- 15554931
TI  - Chemokine receptor expression in the human ectocervix: implications for infection
      by the human immunodeficiency virus-type I.
AB  - Human immunodeficiency virus-type 1 (HIV-1) is a sexually transmitted pathogen
      that can infect cells in the female reproductive tract (FRT). The mechanism of
      viral transmission within the FRT and the mode of viral spread to the periphery
      are not well understood. To characterize the frequency of potential targets of
      HIV infection within the FRT, we performed a systematic study of the expression
      of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and
      CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a
      likely first site of contact with HIV-1 following heterosexual transmission, and
      expression of these receptors is likely to correlate with susceptibility to viral
      infection. We obtained ectocervical tissue specimens from women undergoing
      hysterectomy, and compared expression of these receptors among patients who were
      classified as being in the proliferative or secretory phases of their menstrual
      cycle at the time of hysterectomy, as well as from postmenopausal tissues.
      Epithelial cells from tissues at early and mid-proliferative stages of the
      menstrual cycle express CD4, although by late proliferative and secretory phases,
      CD4 expression was absent or weak. In contrast, GalCer expression was uniform in
      all stages of the menstrual cycle. CXCR4 expression was not detected on
      ectocervical epithelial cells and positive staining was only evident on
      individual leucocytes. In contrast, CCR5 expression was detected on ectocervical
      epithelial cells from tissues at all stages of the menstrual cycle. Overall, our
      results suggest that HIV infection of cells in the ectocervix could most likely
      occur through GalCer and CCR5. These findings are important to define potential
      targets of HIV-1 infection within the FRT, and for the future design of
      approaches to reduce the susceptibility of women to infection by HIV-1.

PMID- 15554933
TI  - Immunoisolated chromaffin cells implanted into the subarachnoid space of rats
      reduce cold allodynia in a model of neuropathic pain: a novel application of
      microencapsulation technology.
AB  - Intrathecal transplants of adrenal medullary chromaffin cells relieve chronic
      pain by secreting catecholamines, opioids, and other neuroactive substances.
      Recently, macrocapsules with semipermeable membranes were used to isolate
      immunologically xenogenic chromaffin cells, but the poor viability in vivo of the
      encapsulated chromaffin cells limited the usefulness of this method. In this
      study, we used a novel method of encapsulation to increase the viability of
      chromaffin cells. We found that microencapsulated chromaffin cells that were
      implanted into the subarachnoid space of rats relieved cold allodynia in a model
      of neuropathic pain. Furthermore, microencapsulated chromaffin cells were
      morphologically normal and retained their functionality. These findings suggest
      that the intrathecal placement of microencapsulated chromaffin cells might be a
      useful method for treating chronic pain.

PMID- 15554934
TI  - In vivo assessment of intact parathyroid hormone adsorption by different dialysis
      membranes during hemodialysis.
AB  - BACKGROUND: Different parathyroid hormone (PTH) behavior during hemodialysis with
      different types of dialysis membranes has been reported. The behavior of intact
      parathyroid hormone (iPTH) adsorption using different dialysis membranes was
      assessed in 12 dialysis patients with secondary hyperparathyroidism. METHODS: The
      study was performed according to a longitudinal scheme comprising three treatment
      modalities, each lasting 2 weeks, for 6 weeks altogether. The first treatment
      consisted of standard bicarbonate dialysis with low-flux polysulfone, followed by
      acetate-free biofiltration with high-flux-polysulfone or with polyacrylonitrile
      AN69. In the first week of each period, dialysis was delivered by using a 1.3
      m(2) surface area and subsequently, a 1.8 m(2) surface area. Intact parathyroid
      hormone was assayed on the blood and dialysate samples to calculate iPTH
      adsorption. RESULTS: The results showed that polyacrylonitrile-AN69 and high-flux
      polysulfone induce a significantly larger drop in PTH serum levels as compared
      with low-flux-polysulfone, particularly in the first half of the dialysis
      session, while the ionized calcium increase is comparable in all different
      hemodialysis treatments. The measurement of iPTH in the dialysate showed lower
      values than those disappearing on the blood side, thus suggesting the presence of
      an adsorptive mechanism in the different dialysis membranes. CONCLUSION: High
      flux polysulfone is endowed with a comparable adsorptive capacity per surface
      unit compared to polyacrylonitrile-AN69, although it seems to show a different
      behavior, as polyacrylonitrile-AN69 saturates early in the first hour of dialysis
      corresponding to its maximum adsorption power, while high-flux-polysulfone
      displays a more lasting adsorptive capacity. Thus, iPTH changes during
      hemodialysis also depend on dialyzer characteristics and the dialysis membrane
      adsorption.

PMID- 15554935
TI  - Factors associated with urea reduction ratio in acute renal failure.
AB  - Prescription and delivery of hemodialysis (HD) in acute renal failure (ARF) may
      be affected by patient-related factors such as hemodynamic instability,
      catabolism, variable extracellular fluid volume, and coagulation disturbances.
      This study was undertaken in a cohort of patients with ARF requiring HD, to
      quantify patient- and dialysis-related variables that influence dialysis
      delivery. The urea reduction ratio (URR) was calculated for each HD session.
      Patient-related variables included age, gender, weight, mean arterial pressure,
      and Acute Physiological and Chronic Health Evaluation (APACHE) II and Multiple
      Organ Failure (MOF) scores. Dialysis-related variables were dialyzer
      characteristics (membrane type, surface area, KoA, and K(UF)), blood flow rate
      (Qb), session length, anticoagulant use, vascular access, and ultrafiltration
      volume. The analysis of factors associated with URR was performed using mixed
      linear statistical models. The cohort consisted of 81 adult patients with ARF who
      underwent 419 consecutive dialysis sessions. Mean (+/- SD) age was 60 +/- 18
      years; 57% were male. At dialysis initiation, APACHE II score was 23 +/- 8 and
      MOF score 2 +/- 1. The number of HD treatments averaged 5.5 +/- 6.1/patient and
      0.8 +/- 0.2/patient/day, mean URR was 54 +/- 15%, and session length 3.2 +/- 1.1
      h; 58% used a femoral venous catheter, and 92% polysulfone dialyzers. Among
      patient-related variables, the only independent predictor of delivered dose of
      dialysis, as measured by URR was the predialysis weight (P < 0.01). Among the
      dialysis-related variables, treatment time (P < 0.01), dialyzer surface area (P <
      0.01), dialyzer K(UF) (P = 0.04), blood flow rate (P < 0.01), and the use of a
      femoral venous catheter (P < 0.01) were also independently associated with URR.
      An interaction between vascular access site and blood flow rate was also found to
      be significant (P < 0.01). This study underscores the importance of the dialysis
      prescription parameters and vascular access site in influencing the dialysis dose
      in critically ill patients, and argues against the importance of patient-related
      characteristics such as disease severity.

PMID- 15554936
TI  - Four years' experience with a miniaturized extracorporeal circulation system and
      its influence on clinical outcome.
AB  - It has been suggested that the morbidity associated with cardiopulmonary bypass
      can be attributed in part to the blood-material and blood-air interactions in the
      extracorporeal circulation (ECC). A recently introduced minimized ECC-system
      (MECC System) should be able to reduce these negative effects associated with
      ECC. A retrospective analysis was performed comprising 485 patients who were
      operated on for elective coronary artery bypass grafting (CABG) using the MECC
      System with intermittent antegrade warm blood cardioplegia (group 1) from January
      2000 to February 2004. A control group consisted of 485 patients (group 2)
      undergoing elective CABG in the same period using a conventional ECC and cold
      crystalloid cardioplegia. There were no significant differences between the two
      groups in terms of the duration of intubation following surgery, the length of
      intensive care unit-stay and the total hospital stay. Although the 30-day
      mortality was similar between the two groups, the incidence of postoperative
      complications and the perioperative use of blood products were significantly
      higher in the control group compared to the MECC group. The MECC System may serve
      as an alternative and less invasive approach to conventional ECC.

PMID- 15554937
TI  - Experimental determination of dynamic characteristics of the VentrAssist
      implantable rotary blood pump.
AB  - The VentrAssist implantable rotary blood pump, intended for long-term ventricular
      assist, is under development and is currently being tested for its rotor-dynamic
      stability. The pump consists of a shaftless impeller, which also acts as the
      rotor of the brushless DC motor. The impeller remains passively suspended in the
      pump cavity by hydrodynamic forces, which result from the small clearances
      between the outside surfaces of the impeller and the pump cavity. These small
      clearances range from approximately 50 microm to 230 microm in size in the
      version of pump reported here. This article presents experimental investigation
      into the dynamic characteristics of the impeller-bearing-pump housing system of
      the rotary blood pump for increasing pump speeds at different flow rates. The
      pump was mounted on a suspension system consisting of a platform and springs,
      where the natural frequency and damping ratio for the suspension system were
      determined. Real-time measurements of the impeller's displacement were performed
      using Hall effect sensors. A vertical disturbance force was exerted onto the pump
      housing, causing the impeller to be displaced in vertical direction from its
      dynamic equilibrium position within the pump cavity. The impeller displacement
      was represented by a decaying sine wave, which indicated the impeller restoring
      to its equilibrium position. From the decaying sine wave the natural frequency
      and stiffness coefficient of the system were determined. Furthermore, the
      logarithmic decrement method was used to determine the damping ratio and
      eventually the damping coefficient of the system. Results indicate that stiffness
      and damping coefficients increased as flow rate and pump speed increased,
      representing an increase in stability with these changing conditions. However,
      pump speed had a greater influence on the stiffness and damping coefficients than
      flow rate did, which was evident through dynamic analysis. Overall the
      experimental method presented in this article was successful in determining the
      dynamic characteristics of the system.

PMID- 15554938
TI  - Acute hemodynamic study of Tai-Ta left ventricular assist device in a canine
      model.
AB  - A revised Tai-Ta centrifugal impeller pump was designed to study the interaction
      of the left ventricular assist device (LVAD) with the cardiovascular system in a
      canine model. Six healthy dogs weighing 12-16 kg were used. Blood flows in the
      aortic arch, the pulmonary artery (PA), and the LVAD outlet were measured
      simultaneously with the arterial blood pressure (ABP), the pump outflow pressure
      (POP), and the electrocardiograph (ECG). Normally, the blood flows in the aorta
      and the PA started at the S-wave of the ECG. When the LVAD was operated at a
      higher rotational speed (increased from 2900 to 5400 rpm), the ABP, POP, the pump
      flow, and the maximum rate of change of PA flow increased. However, the
      fluctuating amplitudes of ABP, POP, and the pump flow decreased significantly.
      The cardiovascular hemodynamics change with the pump speeds. For a typical 1.1
      1.5 L/min cardiac output in canine, the revised LVAD was able to deliver a flow
      bypass ratio from 15% up to 100%. The LVAD outflow appeared to be pulsatile and
      matched the cardiac cycle, showing that the centrifugal impeller pump could be
      used as a pediatric assist device when cardiac function was impeded.

PMID- 15554939
TI  - A minor experimental stenosis in porcine descending thoracic aorta affects the
      spectral content of pressure pulse wave.
AB  - OBJECTIVE: To carry out research into the possible changes of the spectral
      content of pressure pulse wave after the creation of an experimentally induced
      stenosis in the pig descending thoracic aorta. METHODS: Eight healthy,
      normotensive Landrace pigs were subjected to thoracotomy under sterile
      conditions. At the upper segment of the descending thoracic aorta, a 5-mm-long
      circumferential symmetric constriction was imposed and stabilized; hence, a 15-20
      mm Hg pressure gradient was established. Pressure tip catheters were used in
      order to monitor the pressure gradient. Blood flow disturbances were recorded
      through a bidirectional Doppler flow meter at pre- and poststenotic areas (A and
      B, respectively). Measurements were carried out before, 10 min after, and 90 days
      after the creation of the stenosis. The recorded waveforms were analyzed
      mathematically by using Fourier Transform, in order to determine their spectral
      component. Eight sham-operated pigs were used as controls. RESULTS: Fourier
      Transform analysis showed a significant increase (P < 0.05) of spectral content
      in A and B areas. Also, the "relative" harmonic amplitudes in nonstenotic
      subjects were higher than in stenotic animals (P < 0.05). CONCLUSIONS: A minor
      experimental constriction located at the level of the descending thoracic aorta
      increased the spectral content of the pressure pulse wave, indicating that
      spectral analysis may detect slight flow disturbances before developing
      remarkable signs of an impaired circulation system.

PMID- 15554940
TI  - Application of a pressure-relieving air compliance chamber in a single-pulsatile
      extracorporeal life support system: an experimental study.
AB  - Nonpulsatile blood pumps are mainly used in extracorporeal life support systems.
      Although pulsating blood flow is known to be physiological, a pulsatile pump is
      not commonly applied in a circuit with a membrane oxygenator because of damage to
      the blood cells. The hypothesis that the placement of a pressure-relieving
      compliance chamber in a circuit might reduce blood cell trauma was tested. An
      extracorporeal life support circuit was constructed in an acute lung injury model
      of dogs by oleic acid infusion. The animals were divided into three groups. In
      group I (n = 6) a nonpulsatile centrifugal pump was used as a control. In group
      II (n = 4) a single-pulsatile pump was used, and in group III (n = 6) a single
      pulsatile pump equipped with a compliance chamber was used. Pump flow was
      maintained at 1.8-2.0 L/min for 2 h. Hemodynamics and blood gas analyses
      indicated that the pulsatile groups II and III had better results than the
      nonpulsatile group I. The plasma-free hemoglobin level, which indicates blood
      cell trauma, was the lowest in group I and the highest in group II but was
      significantly decreased in group III. A pressure-relieving compliance chamber
      could significantly reduce high circuit pressures and blood cell trauma.

PMID- 15554941
TI  - Transcriptional control of kidney development.
AB  - In recent years, gene inactivation in the mouse and other model systems has shed
      new light on the processes of inductive tissue interactions and morphogenesis.
      These studies have been especially fruitful for understanding the kidney, as this
      organ has been a classical model of organogenesis for more than 50 years and is
      thus well characterized in terms of morphology and inductive properties. One
      outcome of these molecular genetic experiments is that the coordination of kidney
      development appears to be in good part performed at the transcriptional level.
      Many of the gene mutations associated with kidney malformations and disease are
      indeed transcription factors regulating key tissue interaction events. This
      review primarily addresses the role of the most significant transcription factors
      in mouse nephrogenesis.

PMID- 15554942
TI  - Cross-regulation of Wnt signaling and cell adhesion.
AB  - The complex cross-regulation between Wnt signaling, cell-cell adhesion, and cell
      matrix adhesion has revealed a number of regulatory components important in
      development and cancer progression. In the following, we would like to highlight
      and summarize some of the steps where pathways converge or diverge in regulating
      Wnt activity, matrix-induced pathways, and cell adhesion. We would like to focus
      on the involvement of heparan sulfate proteoglycan-rich proteins (HSPGs),
      integrin-mediated outside-in signaling, and cadherin-mediated cell-cell adhesion
      on Wnt pathways and the transcriptional regulation of extracellular matrix
      components and cell adhesion molecules by Wnt signaling.

PMID- 15554943
TI  - Bone marrow-derived mesenchymal stem cells already express specific neural
      proteins before any differentiation.
AB  - Bone marrow mesenchymal stem cells (MSC) are multipotent cells. To explain their
      plasticity, we postulated that undifferentiated MSC may express proteins from
      other tissues such as neuronal tissues. MSC are obtained by two different
      approaches: plastic adhesion or negative depletion (RosetteSep and magnetic beads
      CD45/glycophorin A). MSC are evaluated through FACS analysis using a panel of
      antibodies (SH2, SH3, CD14, CD33, CD34, CD45, etc.). To confirm the
      multipotentiality in vitro, we have differentiated MSC into adipocytes,
      chondrocytes, osteocytes, and neuronal/glial cells using specific induction
      media. We have evaluated neuronal and glial proteins (Nestin, Tuj-I, betaIII
      Tubulin, tyrosine hydroxylase [TH], MAP-2, and GFAP) by using flow cytometry,
      Western blots, and RT-PCR. We found that MSC constituently express native
      immature neuronal proteins such as Nestin and Tuj-1. After only five passages,
      MSC can already express more mature neuronal or glial proteins, such as TH, MAP
      2, and GFAP, without any specific induction. We noticed an increase in the
      expression of more mature neuronal/glial proteins (TH, MAP-2, and GFAP) after
      exposure to neural induction medium, thus confirming the differentiation of MSC
      into neurons and astrocytes. The constitutive expression of Nestin or Tuj-1 by
      MSC suggests that these cells are "multidifferentiated" cells and thus can retain
      the ability for neuronal differentiation, enhancing their potentiality to be
      employed in the treatment of neurological diseases.

PMID- 15554944
TI  - The E protein HEB is preferentially expressed in developing muscle.
AB  - Myogenesis is regulated by the MyoD class of myogenic regulatory factors (MRFs).
      These basic helix-loop-helix transcription factors dimerize with E proteins to
      bind conserved E-box sequences in the promoter regions of muscle-specific genes.
      Perhaps due to their expression in a wide array of tissues, the specific
      interactions of E proteins with different MRFs have been largely ignored.
      Likewise, the expression of E proteins in muscle tissue remains mostly
      uncharacterized. We investigated the expression of the E proteins HEB, E12, and
      E47 in rat L6 myoblasts, which express only embryonic and fast (2X) myosin heavy
      chains (MyHCs) in vitro, C2C12 myosatellite cells, and a number of muscle
      tissues, to determine whether myosin heavy chain diversity is mirrored by
      diversity in E protein or MRF expression. Although L6 and C2C12 myotubes
      demonstrate strong expression of embryonic and 2X (fast) MyHCs,
      immunofluorescence demonstrated the additional expression of type 1 (slow), 2A,
      and 2B MyHCs in the C2C12 cell line. Immunofluorescence and western blot analyses
      show that HEB was expressed in differentiating L6 myoblasts, C2C12 cells, and
      neonatal rat primary myotubes. In contrast, E12 and E47 expression was not
      detected in either cell line or in any adult muscle tissue examined. These data
      strongly implicate HEB in the development of skeletal muscle. However, because
      HEB is expressed in L6 myoblasts, C2C12 myosatellite cells, and neonatal hindlimb
      muscles, it is unlikely to be involved in a fiber type-specific manner, and may
      have a more general role in differentiation of myotubes.

PMID- 15554945
TI  - The bHLH protein MyoR inhibits the differentiation of early embryonic endoderm.
AB  - MyoR is a bHLH protein whose expression was reported to be almost exclusively
      restricted to the precursors of the skeletal muscle lineage where it was
      postulated to function as a transcriptional repressor of myogenesis. However,
      previous studies in our laboratory suggested a much broader role for MyoR in
      embryonic cell differentiation. We demonstrated that, besides being expressed in
      several adult tissues of non-muscle lineage, MyoR was expressed at a much earlier
      stage in mammalian development than had previously been reported, that is, as
      early as the blastocyst stage, well before skeletal muscle specification. We also
      found that, as in skeletal muscle precursor cells, MyoR expression is inversely
      correlated with the cellular differentiative state of ectodermal, non-muscle
      embryonal carcinoma (EC) cells. Retinoic acid (RA) treatment of ectodermal EC or
      embryonal stem (ES) cells promotes their differentiation into primitive endoderm.
      However, in the present study, we show that the RA-induced expression of
      endodermal markers such as EndoA, collagen IV, and t-PA are inhibited by
      exogenous MyoR expression and that the level of inhibition of these markers
      correlates with the level of MyoR expressed. Conversely, knock-down of MyoR
      expression via RNA interference enhances RA-induced differentiation of EC cells,
      promoting earlier and much higher expression of the above-mentioned endodermal
      markers following RA treatment. Finally, we have narrowed the period of exogenous
      MyoR-induced embryonic lethality to between 3.5 and 5.5 days post-coitum (dpc),
      the period during which embryonic endoderm differentiates from the embryonic
      ectoderm. Our results suggest, therefore, that inhibition of endodermal
      differentiation between 3.5 and 5.5 dpc contributes to the embryonic death of
      mouse embryos overexpressing exogenous MyoR and consequently that MyoR may serve
      as a repressor of embryonal endoderm differentiation.

PMID- 15554946
TI  - Craniofacial development in the talpid3 chicken mutant.
AB  - The talpid(3) chicken mutant has a pleiotropic phenotype including polydactyly
      and craniofacial abnormalities. Limb polydactyly in talpid(3) suggests a gain of
      Hedgehog (Hh) signaling, whereas, paradoxically, absence of midline facial
      structures suggests a loss of Hh function. Here we analyze the status of Shh
      signaling in the talpid(3) mutant head. We show that Shh expression domains are
      lost from the talpid(3) head--in hindbrain, midbrain, zona limitans
      intrathalamica, and stomodeal ectoderm--and that direct targets of Hedgehog
      signaling, Ptc1, Ptc2, and Gli1, are also absent even in areas associated with
      primary Shh expression. These data suggest that the talpid(3) mutation leads to
      defective activation of the Shh pathway and, furthermore, that tissue-to-tissue
      transduction of Shh expression in the developing head depends on Hh pathway
      activation. Failure to activate the Shh pathway can also explain absence of floor
      plate and Hnf-3beta and Netrin-1 expression in midbrain and hindbrain and absence
      of Fgf-8 expression in commissural plate. Other aspects of gene expression in the
      talpid(3) head, however, suggest misspecification, such as maintenance of floor
      plate-like gene expression in telencephalon. In branchial arches and lower jaw,
      where Shh is expressed, changes in expression of genes involved in patterning and
      mesodermal specification suggest both gain and loss of Hedgehog function. Thus,
      analysis of gene expression in talpid(3) head shows that, as in talpid(3) limb,
      expression of some genes is lost, while others are ectopically expressed. Unlike
      the limb, many head regions depend on Hh induction of a secondary domain of Shh
      expression, and failure of this induction in talpid(3), together with the
      inability to activate the Shh pathway, explain the loss-of-function head
      phenotype. This gene expression analysis in the talpid(3) head also confirms and
      extends knowledge of the importance of Shh signaling and the balance between
      activation and repression of Shh targets in many aspects of craniofacial
      morphogenesis.

PMID- 15554947
TI  - Sindbis viruses and other alphaviruses as cause of human arthritic disease.
AB  - Amongst the arthritis-causing arboviruses, i.e. those spread by insects, the
      alphavirus group is of special interest. These viruses occasionally cause vast
      outbreaks, such as O'nyong-nyong in Africa in 1959. In Fennoscandia, Sindbis
      related Ockelbo, Pogosta, or Karelian fever viruses have been found to cause
      significant morbidity. The major symptoms in addition to joint inflammation are
      fever, fatigue, headache and rash. The joint symptoms may persist for weeks, even
      months. The diagnosis is based on the clinical picture and serology. The
      causative viruses are closely related but not identical. It appears that at least
      in Finland the Pogosta disease is more common than thought, and the symptoms may
      often be overlooked. Several factors related to the viruses, their hosts, and
      global environmental changes may affect the spread of these viruses. All over the
      world arbovirus-caused diseases have increased, because of global changes.

PMID- 15554948
TI  - The impact of birth weight on coronary heart disease morbidity and mortality in a
      birth cohort followed up for 85 years: a population-based study of men born in
      1913.
AB  - OBJECTIVES: To analyse whether there is a relationship between birth weight on
      the one hand and coronary heart disease (CHD) and cardiovascular disease (CVD)
      mortality and morbidity on the other, whether such a relationship is influenced
      by potential modifying factors from the time of birth, adult height and the
      presence of diabetes, and what significance these possible associations might
      have for the CHD and CVD rates in the general population. DESIGN: Population
      based birth cohort. SETTING: Sweden. SUBJECTS: A total of 1319 singleton men born
      in 1913, surviving until age 20 and from then on followed until 85 years of age.
      MAIN OUTCOME MEASURES: CHD and CVD mortality and morbidity events. RESULTS: The
      gestational age adjusted CHD and CVD mortality and morbidity hazard ratios were
      virtually unaffected by birth weight. Taking possible effect-modifying variables
      into account did not change the results. The population attributable risk
      percentage for CHD and CVD mortality and morbidity due to a birth weight <or=3000
      g was 1% or less. CONCLUSIONS: Birth weight did not significantly affect CHD or
      CVD mortality or morbidity. A birth weight <or=3000 g contributes little to the
      burden of CHD and CVD on a community level.

PMID- 15554949
TI  - The contribution of classical risk factors to cardiovascular disease in familial
      hypercholesterolaemia: data in 2400 patients.
AB  - OBJECTIVE: To determine the contribution of classical risk factors to the
      development of cardiovascular disease (CVD) in patients with heterozygous
      familial hypercholesterolaemia (FH). DESIGN: A retrospective, multi-centre,
      cohort study. Extensive data were collected by scrutinizing medical records and
      the use of questionnaires. Multivariate Cox regression was used to study the
      relationship between potential risk factors and the occurrence of CVD. SETTING
      AND SUBJECTS: We included 2400 FH patients from 27 Dutch lipid clinics. The
      diagnosis of FH was based upon the presence of a low-density lipoprotein receptor
      mutation or upon strict clinical criteria. MAIN OUTCOME MEASURES: Cardiovascular
      mortality and CVD. RESULTS: During 112.943 person-years, 782 (32.6%) patients had
      had at least one cardiovascular event. Male gender (RR 2.82, 95% CI 2.37-3.36),
      smoking (RR 1.67, 95% CI 1.40-1.99), hypertension (RR 1.36, 95% CI 1.06-1.75),
      diabetes mellitus (RR 2.19, 95% CI 1.36-3.54), low HDL-C (RR 1.37, 95% CI 1.15
      1.63) and elevated lipoprotein(a) levels (RR 1.50, 95% CI 1.20-1.79) proved to be
      independent CVD risk factors. These six risk factors explained 18.7% of the
      variation in the occurrence of CVD. CONCLUSIONS: Male gender, smoking,
      hypertension, diabetes mellitus, HDL cholesterol and lipoprotein(a) levels proved
      to be important risk factors for CVD in FH patients. In addition to the routine
      institution of statin therapy, controlling these factors needs special attention
      in the management of this disorder.

PMID- 15554950
TI  - Elevated plasma homocysteine: cause or consequence of myocardial infarction?
AB  - OBJECTIVES: To determine whether a first myocardial infarction leads to increased
      plasma homocysteine concentrations and whether the association between
      homocysteine and myocardial infarction was greater at follow-up compared with
      baseline. DESIGN: A population-based, prospective, nested case-referent study.
      SETTING: Screening took place at the nearest health survey centre in northern
      Sweden. SUBJECTS: Of more than 36,000 persons screened, 78 developed a first
      myocardial infarction (average 18 months after sampling). Fifty of these had
      participated in a follow-up health survey (average 8(1/2) years between surveys)
      and were sex- and age-matched with 56 referents. MAIN OUTCOME MEASURES:
      Comparison of plasma homocysteine levels in case and referent subjects before and
      after development of a first myocardial infarction. RESULTS: No statistically
      significant difference was found between cases and referents regarding
      homocysteine at baseline or follow-up. Plasma homocysteine and plasma creatinine
      increased significantly, and plasma albumin decreased significantly over time.
      Conditional univariate logistic regression indicated that high homocysteine at
      follow-up but not baseline was associated with first myocardial infarction (OR
      2.49; 95% CI: 1.03-6.02), but the relation disappeared in multivariate analyses
      including plasma creatinine and plasma albumin. High plasma creatinine remained
      associated with first myocardial infarction at both baseline (OR 2.94; 95% CI:
      1.05-8.21) and follow-up (OR 3.38; 95% CI: 1.21-9.48). CONCLUSION: In this study,
      first myocardial infarction did not cause increased plasma homocysteine
      concentration.

PMID- 15554951
TI  - The association between total energy intake and early mortality: data from the
      Malmo Diet and Cancer Study.
AB  - OBJECTIVES: In animal studies, low energy intake (EI) has been associated with a
      longer lifespan. We examine whether EI is an independent risk factor for
      prospective all-cause mortality, cardiovascular and cancer mortality in humans.
      DESIGN: Population-based, prospective cohort study. SETTING AND SUBJECTS: The
      Malmo Diet and Cancer Study is a population-based prospective cohort study. A
      total of 28 098 individuals, mean age 58.2 years, completed questionnaires on
      diet and life-style and attended a physical examination during 1991-96. MAIN
      OUTCOME MEASURES: Information on mortality was acquired from national registries
      during a mean follow-up time of 6.6 years. Subjects were categorized by quartiles
      of total EI. The first quartile was used as a reference point in estimating
      multivariate relative risks (RR; 95% CI, Cox's regression model). Adjustments
      were made for confounding by age and various life-style factors. RESULTS: The
      lowest total mortality was observed for women in the third quartile (RR: 0.74;
      CI: 0.57-0.96) and for men in the second and third quartiles (RR: 0.85; CI: 0.69
      1.04 and RR: 0.85; CI: 0.69-1.04 respectively). Similar U-shaped patterns were
      observed for cardiovascular mortality amongst women and cancer mortality amongst
      men. A statistically significant trend (P = 0.029) towards lower cardiovascular
      mortality from the first to the fourth quartile was observed for men.
      CONCLUSIONS: Low caloric consumers did, on average, not have lower mortality than
      average or high caloric consumers. Generally, individuals approximately meeting
      national recommendations for total EI had the lowest mortality. For men, high
      caloric intake was associated with lower cardiovascular mortality.

PMID- 15554952
TI  - Serum cystatin C advantageous compared with serum creatinine in the detection of
      mild but not severe diabetic nephropathy.
AB  - OBJECTIVE: To determine whether serum cystatin C is more accurate than serum
      creatinine in the detection of diabetic nephropathy, also after adjustment for
      age. METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes
      were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance
      (reference method). Cystatin C was measured by a particle-enhanced turbidimetric
      method and creatinine by an enzymatic method. Statistical estimations were
      performed both without and with age adjustment created by z-scores for (51)Cr
      EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular
      filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(
      2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age
      adjusted values (z-scores). RESULTS: Estimations without age adjustment showed
      significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus
      (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when
      using age-adjusted values, the correlation for cystatin C and creatinine,
      respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the
      diagnostic utilities for serum cystatin C versus serum creatinine in manifest
      renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there
      were no significant differences between the two markers whether age adjusted or
      not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or
      z-score -0.84 SD), serum cystatin C is significantly more useful. CONCLUSIONS:
      Serum cystatin C performed better compared with serum creatinine even when
      measured enzymatically, to detect mild diabetic nephropathy. However, serum
      creatinine was as efficient as serum cystatin C to detect advanced diabetic
      nephropathy.

PMID- 15554953
TI  - Antibody levels in adult patients with coeliac disease during gluten-free diet: a
      rapid initial decrease of clinical importance.
AB  - OBJECTIVE: Analysis of antibodies against tissue transglutaminase (tTG) has been
      shown valuable in the diagnosis of coeliac disease (CD) but how quickly serum
      titres decrease after introduction of a gluten-free diet (GFD) is not known in
      adults. CD is a well-recognized disorder amongst the general population and many
      persons try a GFD for fairly vague symptoms before they seek medical advice.
      Therefore, it is important to determine the time that the serologic tests remain
      predictive of the disease after the introduction of a GFD. METHODS: Sera were
      taken from 22 consecutively biopsy-proven adult patients with CD in connection
      with the diagnostic biopsy. The patients were followed for 1 year and sera were
      taken after 1, 3, 6 and 12 months after start of a GFD. Sera were stored at -20
      degrees C and analysed for IgA antibodies against gliadin, endomysium and two
      different commercial tTG assays based on recombinant human tTG (tTGrh) and guinea
      pig liver (tTGgp). RESULTS: Twenty patients could be followed during GFD and all
      antibody titres fell sharply within 1 month after introduction of a GFD and
      continued to decline during the survey interval. Thirty days after beginning the
      diet only 58, 84, 74 and 53% of all patients had positive antibody levels of
      tTGrh, tTGgp, EmA and AGA respectively. CONCLUSIONS: As the antibodies used to
      confirm the diagnosis of CD fall rapidly and continue to decline following the
      introduction of a GFD, it is important that health care providers carefully
      inquire about the possibility of self-prescribed diets before patients sought
      medical attention.

PMID- 15554954
TI  - Fatal voluntary salt intake resulting in the highest ever documented sodium
      plasma level in adults (255 mmol L-1): a disorder linked to female gender and
      psychiatric disorders.
AB  - Excessive ingestion of salt is a well-recognized cause of hypernatraemia in
      children, is uncommonly recognized in debilitated elderly persons, but is rarely
      diagnosed in healthy, independent adults. We report a case of fatal salt
      poisoning in a 20-year-old lady who suffered of post-natal depression and
      ingested large quantities of salt as part of exorcism ritual. She presented with
      the highest ever documented serum sodium level of 255 mmol L(-1), associated with
      severe neurological impairment that was unresponsive to aggressive hypotonic
      fluid replacement. Post-mortem examination ruled out any other possible probable
      cause of death. The medical literature was reviewed, and 16 previous cases of
      severe hypernatraemia in adults secondary to excessive salt ingestion were
      retrieved. Common features of all reported cases included female gender (95% of
      cases) and evidence of underlying cognitive or psychiatric disorders (all
      reported cases). We conclude that women with documented cognitive or psychiatric
      disorders, in particular depression, are susceptible for psychogenic salt
      poisoning. Awareness should be raised to the potentially life-risking use of
      salty beverages as emetics or as part of 'exorcism' rituals.

PMID- 15554955
TI  - A reappraisal of the Barcelona Clinic Liver Cancer model: natural history of
      untreated 'intermediate stage' hepatocellular carcinoma.

PMID- 15554957
TI  - Bacterial subcellular architecture: recent advances and future prospects.
AB  - Traditional textbook representations of the prokaryotic cytoplasm show an
      amorphous, unstructured amalgamation of proteins and small molecules in which a
      randomly arranged chromosome resides. The development and application of a swathe
      of microscopic techniques over the last 10 years in particular, has shown this
      image of the microbial cell to be incorrect: the cytoplasm is highly structured
      with many proteins carrying out their assigned functions at specific subcellular
      locations; bacteria contain cytoskeletal elements including microtubule, actin
      and intermediate filament homologues; the chromosome is not randomly folded and
      is organized in such a way as to facilitate efficient segregation upon cell
      division. This review will concentrate on recent advances in our understanding of
      subcellular architecture and the techniques that have led to these discoveries.

PMID- 15554958
TI  - Genetic recombination and the cell cycle: what we have learned from chromosome
      dimers.
AB  - Genetic recombination is central to DNA metabolism. It promotes sequence
      diversity and maintains genome integrity in all organisms. However, it can have
      perverse effects and profoundly influence the cell cycle. In bacteria harbouring
      circular chromosomes, recombination frequently has an unwanted outcome, the
      formation of chromosome dimers. Dimers form by homologous recombination between
      sister chromosomes and are eventually resolved by the action of two site-specific
      recombinases, XerC and XerD, at their target site, dif, located in the
      replication terminus of the chromosome. Studies of the Xer system and of the
      modalities of dimer formation and resolution have yielded important knowledge on
      how both homologous and site-specific recombination are controlled and integrated
      in the cell cycle. Here, we briefly review these advances and highlight the
      important questions they raise.

PMID- 15554959
TI  - Protein-protein interactions within the Fatty Acid Synthase-II system of
      Mycobacterium tuberculosis are essential for mycobacterial viability.
AB  - Despite the existence of efficient chemotherapy, tuberculosis remains a leading
      cause of mortality worldwide. New drugs are urgently needed to reduce the
      potential impact of the emergence of multidrug-resistant strains of the causative
      agent Mycobacterium tuberculosis (Mtb). The front-line antibiotic isoniazid
      (INH), and several other drugs, target the biosynthesis of mycolic acids and
      especially the Fatty Acid Synthase-II (FAS-II) elongation system. This
      biosynthetic pathway is essential and specific for mycobacteria and still
      represents a valuable system for the search of new anti-tuberculous agents.
      Several data, in the literature, suggest the existence of protein-protein
      interactions within the FAS-II system. These interactions themselves might serve
      as targets for a new generation of drugs directed against Mtb. By using an
      extensive in vivo yeast two-hybrid approach and in vitro co-immunoprecipitation,
      we have demonstrated the existence of both homotypic and heterotypic interactions
      between the known components of FAS-II. The condensing enzymes KasA, KasB and
      mtFabH interact with each other and with the reductases MabA and InhA.
      Furthermore, we have designed and constructed point mutations of the FAS-II
      reductase MabA, able to disrupt its homotypic interactions and perturb the
      interaction pattern of this protein within FAS-II. Finally, we showed by a
      transdominant genetic approach that these mutants are dominant negative in both
      non-pathogenic and pathogenic mycobacteria. These data allowed us to draw a
      dynamic model of the organization of FAS-II. They also represent an important
      step towards the design of a new generation of anti-tuberculous agents, as being
      inhibitors of essential protein-protein interactions.

PMID- 15554960
TI  - Mitochondrial beta-oxidation in Aspergillus nidulans.
AB  - Beta-oxidation (beta-ox) occurs exclusively in the peroxisomes of Saccharomyces
      cerevisiae and other yeasts, leading to the supposition that fungi lack
      mitochondrial beta-ox. Here we present unequivocal evidence that the filamentous
      fungus Aspergillus nidulans houses both peroxisomal and mitochondrial beta-ox.
      While growth of a peroxisomal beta-ox disruption mutant (DeltafoxA) was
      eliminated on a very long-chain fatty acid (C(22:1)), growth was only partially
      impeded on a long-chain fatty acid (C(18:1)) and was not affected at all on short
      chain (C4-C6) fatty acids. In contrast, growth of a putative enoyl-CoA hydratase
      mutant (DeltaechA) was abolished on short-chain and severely restricted on long-
      and very long-chain fatty acids. Furthermore fatty acids inhibited growth of the
      DeltaechA mutant but not the DeltafoxA mutant in the presence of an alternate
      carbon source (lactose). Disruption of echA led to a 28-fold reduction in 2
      butenoyl-CoA hydratase activity in a preparation of organelles. EchA was also
      required for growth on isoleucine and valine. The subcellular localization of the
      FoxA and EchA proteins was confirmed through the use of red and green fluorescent
      protein fusions.

PMID- 15554961
TI  - The related effector proteins SopD and SopD2 from Salmonella enterica serovar
      Typhimurium contribute to virulence during systemic infection of mice.
AB  - Salmonella resides within host cells in a vacuole that it modifies through the
      action of virulence proteins called effectors. Here we examined the role of two
      related effectors, SopD and SopD2, in Salmonella pathogenesis. Salmonella
      enterica serovar Typhimurium (S. Typhimurium) mutants lacking either sopD or
      sopD2 were attenuated for replication in the spleens of infected mice when
      competed against wild-type bacteria in mixed infection experiments. A double
      mutant lacking both effector genes did not display an additive attenuation of
      virulence in these experiments. The double mutant also competed equally with both
      of the single mutants. Deletion of either effector impaired bacterial replication
      in mouse macrophages but not human epithelial cells. Deletion of sopD2 impaired
      Salmonella's ability to form tubular membrane filaments [Salmonella-induced
      filaments (Sifs)] in infected cells; the number of Sifs decreased, whereas the
      number of pseudo-Sifs (thought to be a precursor of Sifs) was increased.
      Transfection of HeLa cells with the effector SifA induced the formation of Sif
      like tubules and these were observed in greater size and number after co
      transfection of SifA with SopD2. In infected cells, SifA and SopD2 were localized
      both to Sifs and to pseudo-Sifs. In contrast, deletion of sopD had no effect on
      Sif formation. Our results indicate that both SopD and SopD2 contribute to
      virulence in mice and suggest a functional relationship between these two
      proteins during systemic infection of the host.

PMID- 15554962
TI  - Energetic components VirD4, VirB11 and VirB4 mediate early DNA transfer reactions
      required for bacterial type IV secretion.
AB  - Bacteria use type IV secretion systems (T4SS) to translocate DNA (T-DNA) and
      protein substrates across the cell envelope. By transfer DNA immunoprecipitation
      (TrIP), we recently showed that T-DNA translocates through the Agrobacterium
      tumefaciens VirB/D4 T4SS by forming close contacts sequentially with the VirD4
      receptor, VirB11 ATPase, the inner membrane subunits VirB6 and VirB8 and,
      finally, VirB2 pilin and VirB9. Here, by TrIP, we show that nucleoside
      triphosphate binding site (Walker A motif) mutations do not disrupt VirD4
      substrate binding or transfer to VirB11, suggesting that these early reactions
      proceed independently of ATP binding or hydrolysis. In contrast, VirD4, VirB11
      and VirB4 Walker A mutations each arrest substrate transfer to VirB6 and VirB8,
      suggesting that these subunits energize this transfer reaction by an ATP
      dependent mechanism. By co-immunoprecipitation, we supply evidence for VirD4
      interactions with VirB4 and VirB11 independently of other T4SS subunits or intact
      Walker A motifs, and with the bitopic inner membrane subunit VirB10. We
      reconstituted substrate transfer from VirD4 to VirB11 and to VirB6 and VirB8 by
      co-synthesis of previously identified 'core' components of the VirB/D4 T4SS. Our
      findings define genetic requirements for DNA substrate binding and the early
      transfer reactions of a bacterial type IV translocation pathway.

PMID- 15554963
TI  - A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans
      morphology.
AB  - Candida albicans is an opportunistic pathogen that is commonly found as a member
      of the human microflora. The ability of C. albicans to alter its cellular
      morphology has been associated with its virulence; yeast cells are more prevalent
      in commensal interactions whereas filamentous cells appear important in
      opportunistic infections. C. albicans encounters a multitude of other microbial
      species in the host environment and it is likely that they impact the C. albicans
      transition between virulent and non-virulent states. Here, we report that C.
      albicans morphology is significantly affected by the presence of Pseudomonas
      aeruginosa, another opportunistic pathogen. In a screen using a C. albicans HWP1
      lacZ strain to indicate regions of filamentous growth, we identified P.
      aeruginosa mutants incapable of inhibiting C. albicans filamentation. Through
      these studies, we found that 3-oxo-C12 homoserine lactone, a cell-cell signalling
      molecule produced by P. aeruginosa, was sufficient to inhibit C. albicans
      filamentation without affecting fungal growth rates. Both microscopic analysis
      and real-time reverse transcription polymerase chain reaction analysis of
      morphology-specific markers confirmed that filamentation was suppressed by 200
      microM 3-oxo-C12 homoserine lactone. Structurally related compounds with a 12
      carbon chain length, e.g. C12-acyl homoserine lactone and dodecanol also affected
      C. albicans filamentation at similar concentrations. In contrast, other acylated
      homoserine lactones of different chain lengths did not affect fungal morphology.
      The activity of 3OC12HSL is compared with that of farnesol, a C. albicans
      produced molecule also with a C12-backbone. The effects that bacteria have on the
      morphology of C. albicans represents one of the ways by which bacteria can
      influence the behaviour of fungal cells.

PMID- 15554964
TI  - A potential role for ICP, a Leishmanial inhibitor of cysteine peptidases, in the
      interaction between host and parasite.
AB  - The biological role of a natural inhibitor of cysteine peptidases (designated
      ICP) of Leishmania has been investigated by genetic manipulation of the parasite.
      Null mutants grew normally in vitro, were as infective to macrophages in vitro as
      wild-type parasites, but had reduced infectivity to mice. Mutants re-expressing
      ICP from a single gene gave partial restoration of virulence in vivo, whereas
      mutants overexpressing ICP secreted the inhibitor and showed markedly reduced
      virulence in mice. Promastigotes of the null mutants had similar cysteine
      peptidase activities as the wild-type parasites, suggesting that ICP is not
      required for the expression or processing of the enzymes. The only proteins found
      to bind to ICP in promastigote cell lysates were fully processed forms of CPA and
      CPB, showing that ICP does not bind in abundance either to zymogens of the
      cysteine peptidases or other leishmanial proteins. However, only a small
      proportion of ICP colocalized with CPA and CPB in the promastigote (in the
      endoplasmic reticulum and Golgi) and the majority of ICP resided in vesicles that
      are apparently distinct from endosomes and the multivesicular tubule (MVT)
      lysosome. These data suggest that ICP has a role other than modulation of the
      activity of the parasite's own cysteine peptidases and their normal trafficking
      to the MVT-lysosome via the flagellar pocket. The finding that ICP partially
      colocalized with an endocytosed cysteine peptidase leads us to postulate that ICP
      has a role in protection of the parasite against the hydrolytic environment of
      the sandfly gut and/or the parasitophorous vacuole of host macrophages.

PMID- 15554965
TI  - Identification of a polar targeting determinant for Bacillus subtilis DivIVA.
AB  - The Bacillus subtilis protein DivIVA controls both the positioning of the
      vegetative cell division site and the polar attachment of the chromosome during
      sporulation. In vegetative growth DivIVA attracts the bipartite cell division
      inhibitor MinCD away from the cell centre and towards the cell pole. This process
      ensures the inactivation of old polar division sites and leaves the cell centre
      free for the assembly of a new cell division complex. During sporulation MinCD
      and DivIVA levels fall, but DivIVA remains at the cell poles and becomes involved
      in the migration of the chromosomes to the pole. In order to investigate polar
      targeting of DivIVA, we undertook a mutational analysis of the 164-amino-acid
      protein. These studies identified one mutant (divIVA(R18C)) that could not
      localize to the cell pole but which retained the ability to support both
      vegetative growth and 50% sporulation efficiency. Further analysis revealed that,
      in the absence of polar targeting, DivIVA(R18C) localized to the nucleoid during
      vegetative growth in a Spo0J/Soj-dependent manner and required Spo0J/Soj and MinD
      to orientate the chromosomes correctly during sporulation. We demonstrate that
      polar targeting of DivIVA(R18C) is not essential during vegetative growth because
      the mutant can recognize the cell division site and influences the localization
      of MinD. Similarly we show that DivIVA(R18C) can function during sporulation
      because it can support the Spo0J/Soj orientation of the chromosome. In addition,
      we establish that both residues 18 and 19 constitute a DivIVA polar targeting
      determinant.

PMID- 15554966
TI  - CovS/CovR of group B streptococcus: a two-component global regulatory system
      involved in virulence.
AB  - In this study, we carried out a detailed structural and functional analysis of a
      Streptococcus agalactiae (GBS) two-component system which is orthologous to the
      CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes. In GBS, covR
      and covS are part of a seven gene operon transcribed from two promoters that are
      not regulated by CovR. A DeltacovSR mutant was found to display dramatic
      phenotypic changes such as increased haemolytic activity and reduced CAMP
      activity on blood agar. Adherence of the DeltacovSR mutant to epithelial cells
      was greatly increased and analysis by transmission electron microscopy revealed
      the presence at its surface of a fibrous extracellular matrix that might be
      involved in these intercellular interactions. However, the DeltacovSR mutant was
      unable to initiate growth in RPMI and its viability in human normal serum was
      greatly impaired. A major finding of this phenotypic analysis was that the
      CovS/CovR system is important for GBS virulence, as a 3 log increase of the
      LD(50) of the mutant strain was observed in the neonate rat sepsis model. The
      pleiotropic phenotype of the DeltacovSR mutant is in full agreement with the
      large number of genes controlled by CovS/CovR as seen by expression profiling
      analysis, many of which encode potentially secreted or cell surface-associated
      proteins: 76 genes are repressed whereas 63 were positively regulated. CovR was
      shown to bind directly to the regulatory regions of several of these genes and a
      consensus CovR recognition sequence was proposed using both DNase I footprinting
      and computational analyses.

PMID- 15554967
TI  - The Campylobacter jejuni dccRS two-component system is required for optimal in
      vivo colonization but is dispensable for in vitro growth.
AB  - A Campylobacter jejuni two-component signal transduction system (TCSTS),
      designated dccR-dccS (diminished capacity to colonize; Cj1223c-Cj1222c), has been
      found to be important for in vivo colonization but dispensable for in vitro
      growth. A DeltadccR response regulator mutant generated using the virulent strain
      81-176 background exhibited significantly reduced colonization of immunocompetent
      limited flora (I-LF) mice, severe combined immunodeficient limited flora (SCID
      LF) mice, and 1-day-old chicks. A DeltadccS sensor kinase mutant was likewise
      defective for colonization in the I-LF mouse model. DeltadccR-infected SCID-LF
      mice also exhibited dramatically reduced inflammation relative to wild type
      infected SCID-LF mice. Despite this diminished colonization capacity, the
      DeltadccRS mutants were indistinguishable from wild type for growth under
      numerous in vitro conditions as well as for various phenotypes. Microarray
      analysis identified several genes encoding putative periplasmic and membrane
      proteins as being regulated by this two-component system; binding of purified His
      tagged DccR to the promoter region of two of these genes supports a direct
      protein-DNA interaction. A conserved repeat sequence was identified in the
      promoter regions of these genes and in three other promoter regions in the
      genome, including that of an operon encoding a putative type I secretion system.
      Two of the regulated target genes were found to be essential for optimal
      colonization. Both the two-component system and the putative regulated genes have
      uncharacterized homologues in other Campylobacter and Helicobacter spp.,
      suggesting that they may perform an important function in colonization among a
      variety of related pathogenic species.

PMID- 15554968
TI  - Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S
      ribosomal subunit from Deinococcus radiodurans in complex with tiamulin.
AB  - Tiamulin, a prominent member of the pleuromutilin class of antibiotics, is a
      potent inhibitor of protein synthesis in bacteria. Up to now the effect of
      pleuromutilins on the ribosome has not been determined on a molecular level. The
      3.5 A structure of the 50S ribosomal subunit from Deinococcus radiodurans in
      complex with tiamulin provides for the first time a detailed picture of its
      interactions with the 23S rRNA, thus explaining the molecular mechanism of the
      antimicrobial activity of the pleuromutilin class of antibiotics. Our results
      show that tiamulin is located within the peptidyl transferase center (PTC) of the
      50S ribosomal subunit with its tricyclic mutilin core positioned in a tight
      pocket at the A-tRNA binding site. Also, the extension, which protrudes from its
      mutilin core, partially overlaps with the P-tRNA binding site. Thereby, tiamulin
      directly inhibits peptide bond formation. Comparison of the tiamulin binding site
      with other PTC targeting drugs, like chloramphenicol, clindamycin and
      streptogramins, may facilitate the design of modified or hybridized drugs that
      extend the applicability of this class of antibiotics.

PMID- 15554969
TI  - Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl
      transferase centre are associated with reduced susceptibility to tiamulin in
      Brachyspira spp. isolates.
AB  - The pleuromutilin antibiotic tiamulin binds to the ribosomal peptidyl transferase
      centre. Three groups of Brachyspira spp. isolates with reduced tiamulin
      susceptibility were analysed to define resistance mechanisms to the drug.
      Mutations were identified in genes encoding ribosomal protein L3 and 23S rRNA at
      positions proximal to the peptidyl transferase centre. In two groups of
      laboratory-selected mutants, mutations were found at nucleotide positions 2032,
      2055, 2447, 2499, 2504 and 2572 of 23S rRNA (Escherichia coli numbering) and at
      amino acid positions 148 and 149 of ribosomal protein L3 (Brachyspira pilosicoli
      numbering). In a third group of clinical B. hyodysenteriae isolates, only a
      single mutation at amino acid 148 of ribosomal protein L3 was detected. Chemical
      footprinting experiments show a reduced binding of tiamulin to ribosomal subunits
      from mutants with decreased susceptibility to the drug. This reduction in drug
      binding is likely the resistance mechanism for these strains. Hence, the
      identified mutations located near the tiamulin binding site are predicted to be
      responsible for the resistance phenotype. The positions of the mutated residues
      relative to the bound drug advocate a model where the mutations affect tiamulin
      binding indirectly through perturbation of nucleotide U2504.

PMID- 15554970
TI  - An alternative pathway for reduced folate biosynthesis in bacteria and halophilic
      archaea.
AB  - Whereas tetrahydrofolate is an essential cofactor in all bacteria, the gene that
      encodes the enzyme dihydrofolate reductase (DHFR) could not be identified in many
      of the bacteria whose genomes have been entirely sequenced. In this communication
      we show that the halophilic archaea Halobacterium salinarum and Haloarcula
      marismortui contain genes coding for proteins with an N-terminal domain
      homologous to dihydrofolate synthase (FolC) and a C-terminal domain homologous to
      dihydropteroate synthase (FolP). These genes are able to complement a Haloferax
      volcanii mutant that lacks DHFR. We also show that the Helicobacter pylori
      dihydropteroate synthase can complement an Escherichia coli mutant that lacks
      DHFR. Activity resides in an N-terminal segment that is homologous to the
      polypeptide linker that connects the dihydrofolate synthase and dihydropteroate
      synthase domains in the haloarchaeal enzymes. The purified recombinant H. pylori
      dihydropteroate synthase was found to be a flavoprotein.

PMID- 15554971
TI  - Two minimal Tat translocases in Bacillus.
AB  - Activity of the Tat machinery for protein transport across the inner membrane of
      Escherichia coli and the chloroplast thylakoidal membrane requires the presence
      of three membrane proteins: TatA, TatB and TatC. Here, we show that the Tat
      machinery of the Gram-positive bacterium Bacillus subtilis is very different
      because it contains at least two minimal Tat translocases, each composed of one
      specific TatA and one specific TatC component. A third, TatB-like component is
      apparently not required. This implies that TatA proteins of B. subtilis perform
      the functions of both TatA and TatB of E. coli and thylakoids. Notably, the two
      B. subtilis translocases named TatAdCd and TatAyCy both function as individual,
      substrate-specific translocases for the twin-arginine preproteins PhoD and YwbN,
      respectively. Importantly, these minimal TatAC translocases of B. subtilis are
      representative for the Tat machinery of the vast majority of Gram-positive
      bacteria, Streptomycetes being the only known exception with TatABC translocases.

PMID- 15554972
TI  - Positive control of tylosin biosynthesis: pivotal role of TylR.
AB  - Control of tylosin production in Streptomyces fradiae features interplay between
      a repressor, TylQ, and an activator, TylS, during regulation of tylR. The latter
      encodes a pathway-specific activator that controls most of the tylosin
      biosynthetic (tyl) genes that are subject to regulation. This was established by
      targeted gene disruption applied separately to tylR and tylS together with
      transcript analysis involving reverse transcription polymerase chain reaction (RT
      PCR). TylR controls multiple genes that encode the synthesis or addition of all
      three tylosin sugars, plus polyketide ring oxidation, and at least one of the
      polyketide synthase (PKS) megagenes, tylGI. (Expression of a few tyl genes, plus
      the resistance determinants tlrB and tlrD, together with some ancillary or
      unassigned genes, is not apparently regulated during fermentation, consistent
      with constitutive expression.) In contrast, the only gene known for sure to be
      directly controlled by TylS is tylR, and there are very few additional
      candidates. These include the mycinose-biosynthetic gene, tylJ, and two
      previously unassigned genes, ORF12* (tylU) plus ORF11* (tylV). TylS also controls
      the PKS genes [tylGIII-tylGIV-tylGV] although not in obligatory fashion. These
      genes can be transcribed (i.e. tylosin can be produced) in a tylS-KO strain by
      forcing overexpression of tylR using a foreign promoter. We therefore suspect
      that TylS might control the PKS genes indirectly, although this remains to be
      established unequivocally. Conceivably, the direct effects of TylS are exerted
      exclusively on other regulators. Tylosin production levels were elevated when
      tylS or (especially) tylR was overexpressed in S. fradiae wild-type and yield
      increments of industrial significance were generated by similar manipulation of
      an enhanced production strain.

PMID- 15554973
TI  - Transcriptional profiling in Candida albicans reveals new adaptive responses to
      extracellular pH and functions for Rim101p.
AB  - The human pathogen Candida albicans grows and colonizes sites that can vary
      markedly in pH. The pH response in C. albicans is governed in part by the Rim101p
      pathway. In Saccharomyces cerevisiae, Rim101p promotes alkaline responses by
      repressing expression of NRG1, itself a transcriptional repressor. Our studies
      reveal that in C. albicans, Rim101p-mediated alkaline adaptation is not through
      repression of CaNRG1. Furthermore, our studies suggest that Rim101p and Nrg1p act
      in parallel pathways to regulate hyphal morphogenesis, an important contributor
      to virulence. To determine the wild-type C. albicans transcriptional response to
      acidic and alkaline pH, we utilized microarrays and identified 514 pH-responsive
      genes. Of these, several genes involved in iron acquisition were upregulated at
      pH 8, suggesting that alkaline pH induces iron starvation. Microarray analysis of
      rim101-/- cells indicated that Rim101p does not govern transcriptional responses
      at acidic pH, but does regulate a subset of transcriptional responses at alkaline
      pH, including the iron acquisition genes. We found that rim101-/- cells are
      sensitive to iron starvation, which suggests that one important aspect of the
      Rim101p-dependent alkaline pH response is to adapt to iron starvation conditions.

PMID- 15554974
TI  - A conservative amino acid change alters the function of BosR, the redox regulator
      of Borrelia burgdorferi.
AB  - Borrelia burgdorferi, the aetiologic agent of Lyme disease, modulates gene
      expression in response to changes imposed by its arthropod vector and mammalian
      hosts. As reactive oxygen species (ROS) are known to vary in these environments,
      we asked how B. burgdorferi responds to oxidative stress. The B. burgdorferi
      genome encodes a PerR homologue (recently designated BosR) that represses the
      oxidative stress response in other bacteria, suggesting a similar function in B.
      burgdorferi. When we tested the sensitivity of B. burgdorferi to ROS, one clonal
      non-infectious B. burgdorferi isolate exhibited hypersensitivity to t-butyl
      hydroperoxide when compared with infectious B. burgdorferi and other non
      infectious isolates. Sequence analysis indicated that the hypersensitive non
      infectious isolates bosR allele contained a single nucleotide substitution,
      converting an arginine to a lysine (bosRR39K). Mutants in bosRR39K exhibited an
      increase in resistance to oxidative stressors when compared with the parental non
      infectious strain, suggesting that BosRR39K functioned as a repressor.
      Complementation with bosRR39K and bosR resulted in differential sensitivity to t
      butyl hydroperoxide, indicating that these alleles are functionally distinct. In
      contrast to BosR, BosRR39K did not activate transcription of a napA promoter-lacZ
      reporter in Escherichia coli nor bind the napA promoter/operator domain. However,
      we found that both BosR and BosRR39K bound to the putative promoter/operator
      region of superoxide dismutase (sodA). In addition, we determined that cells
      lacking BosRR39K synthesized fourfold greater levels of the decorin binding
      adhesin DbpA suggesting that BosRR39K regulates genes unrelated to oxidative
      stress. Based on these data, we propose that the single amino acid substitution,
      R39K, dramatically alters the activity of BosR by altering its ability to bind
      DNA at target regulatory sequences.

PMID- 15554975
TI  - The ATP-dependent ClpXP and Lon proteases regulate expression of the Yersinia
      pestis type III secretion system via regulated proteolysis of YmoA, a small
      histone-like protein.
AB  - The Yersinia pestis plasmid pCD1-encoded type III secretion system (T3SS) is
      essential for the pathogenicity of Y. pestis in mammalian hosts. T3SS-associated
      genes are maximally expressed at 37 degrees C in the absence of extracellular
      calcium. Expression of T3SS genes requires LcrF, an AraC-like transcriptional
      activator, and is repressed by YmoA, a small histone-like protein. The mechanism
      by which temperature regulates T3SS gene expression has not been determined;
      however, changes in DNA topology have been implicated in this process. We report
      here that a Y. pestis strain deficient in production of the ClpXP and Lon
      proteases does not express a functional T3SS partly because of high cytosolic
      levels of YmoA. YmoA is rapidly degraded at 37 degrees C in wild-type Y. pestis,
      but remains stable in a clpXPlon deletion mutant. The stability of YmoA in wild
      type Y. pestis increased as the growth temperature of the culture decreased; in
      contrast, YmoA was stable at all temperatures examined in the clpXPlon deletion
      mutant. These results indicate that the ClpXP and Lon proteases contribute to the
      environmental regulation of the Y. pestis T3SS system through regulated
      proteolysis of YmoA.

PMID- 15554976
TI  - The Caulobacter crescentus GTPase CgtAC is required for progression through the
      cell cycle and for maintaining 50S ribosomal subunit levels.
AB  - The Obg subfamily of bacterial GTP-binding proteins are biochemically distinct
      from Ras-like proteins raising the possibility that they are not controlled by
      conventional guanine nucleotide exchange factors (GEFs) and/or guanine nucleotide
      activating proteins (GAPs). To test this hypothesis, we generated mutations in
      the Caulobacter crescentus obg gene (cgtAC) which, in Ras-like proteins, would
      result in either activating or dominant negative phenotypes. In C. crescentus, a
      P168V mutant is not activating in vivo, although in vitro, the P168V protein
      showed a modest reduction in the affinity for GDP. Neither the S173N nor N280Y
      mutations resulted in a dominant negative phenotype. Furthermore, the S173N was
      significantly impaired for GTP binding, consistent with a critical role of this
      residue in GTP binding. In general, conserved amino acids in the GTP-binding
      pocket were, however, important for function. To examine the in vivo consequences
      of depleting CgtAC, we generated a temperature-sensitive mutant, G80E. At the
      permissive temperature, G80E cells grow slowly and have reduced levels of 50S
      ribosomal subunits, indicating that CgtAC is important for 50S assembly and/or
      stability. Surprisingly, at the non-permissive temperature, G80E cells rapidly
      lose viability and yet do not display an additional ribosome defect. Thus, the
      essential nature of the cgtAC gene does not appear to result from its ribosome
      function. G80E cells arrest as predivisional cells and stalkless cells. Flow
      cytometry on synchronized cells reveals a G1-S arrest. Therefore, CgtAC is
      necessary for DNA replication and progression through the cell cycle.

PMID- 15554977
TI  - The C-terminal domains of the gingipain K polyprotein are necessary for assembly
      of the active enzyme and expression of associated activities.
AB  - The Porphyromonas gingivalis lysine-specific cysteine protease (gingipain K, Kgp)
      is expressed as a large precursor protein consisting of a leader sequence, a pro
      fragment, a catalytic domain with a C-terminal IgG-like subdomain (IgSF) and a
      large haemagglutinin/adhesion (HA) domain. In order to directly study the role of
      these non-catalytic domains in pro-Kgp processing and maturation in P.
      gingivalis, the wild-type form of the gene was replaced with deletion variants
      encoding C-terminally truncated proteins, including KgpDeltaHA3/4 (Delta1292-1732
      aa), KgpDeltaHA2-4 (Delta1157-1732 aa), KgpDeltaHA1-4 (Delta738-1732 aa),
      KgpDeltaC-term/HA (Delta681-1732 aa) and KgpDeltaIg/C-term/HA (602-1732 aa).
      Northern blot and reverse transcription polymerase chain reaction (RT-PCR)
      analysis revealed that all truncated variants of the kgp gene were transcribed in
      P. gingivalis. Despite high levels of kgpDeltaC-term/HA and kgpDeltaIg/C-term/HA
      transcripts, no Kgp-specific antigen was detected in cultures of these mutants as
      determined by Western blot analysis with monoclonal antibodies specific for the
      Kgp catalytic domain. Furthermore, only barely measurable amounts of Kgp-specific
      activity were detected in these two mutants. The remaining mutants expressed
      significant Kgp activity, however, at lower levels when compared with the
      parental strain. The decreased activity most probably resulted from altered
      folding and/or hindered secretion of the protein. The kgp gene truncation was
      also demonstrated to alter the distribution of the gingipain protein between
      membrane-associated and -secreted forms. While both gingipain K activity and the
      protein were cell membrane-associated in the parental strain, the mutants
      released significant amounts of both protein and activity into the media. Taken
      together, these results suggest that the C-terminal HA domains of Kgp are not
      only essential for full expression of gingipain activity, but also for proper
      processing of the multiprotein complex assembly on the P. gingivalis outer
      membrane. Moreover, our results indicate that the immunoglobulin-like subdomain
      is indispensable for proper folding and expression of the gingipains.

PMID- 15554978
TI  - Physical and functional interactions among RNase E, polynucleotide phosphorylase
      and the cold-shock protein, CsdA: evidence for a 'cold shock degradosome'.
AB  - Escherichia coli contains at least five ATP-dependent DEAD-box RNA helicases
      which may play important roles in macromolecular metabolism, especially in
      translation and mRNA decay. Here we demonstrate that one member of this family,
      CsdA, whose expression is induced by cold shock, interacts physically and
      functionally with RNase E. Three independent approaches show that after a shift
      of cultures to 15 degrees C, CsdA co-purifies with RNase E and other components
      of the RNA degradosome. Moreover, functional assays using reconstituted minimal
      degradosomes prepared from purified components in vitro show that CsdA can fully
      replace the resident RNA helicase of the RNA degradosome, RhlB. In addition,
      under these conditions, CsdA displays RNA-dependent ATPase activity. Taken
      together, our data are consistent with a model in which CsdA accumulates during
      the early stages of cold acclimatization and subsequently assembles into
      degradosomes with RNase E synthesized in cold-adapted cultures. These findings
      show that the RNA degradosome is a flexible macromolecular machine capable of
      adapting to altered environmental conditions.

PMID- 15554979
TI  - The RNase E of Escherichia coli has at least two binding sites for DEAD-box RNA
      helicases: functional replacement of RhlB by RhlE.
AB  - The non-catalytic region of Escherichia coli RNase E contains a protein scaffold
      that binds to the other components of the RNA degradosome. Alanine scanning
      yielded a mutation, R730A, that disrupts the interaction between RNase E and the
      DEAD-box RNA helicase, RhlB. We show that three other DEAD-box helicases, SrmB,
      RhlE and CsdA also bind to RNase E in vitro. Their binding differs from that of
      RhlB because it is not affected by the R730A mutation. Furthermore, the deletion
      of residues 791-843, which does not affect RhlB binding, disrupts the binding of
      SrmB, RhlE and CsdA. Therefore, RNase E has at least two RNA helicase binding
      sites. Reconstitution of a complex containing the protein scaffold of RNase E,
      PNPase and RhlE shows that RhlE can furnish an ATP-dependent activity that
      facilitates the degradation of structured RNA by PNPase. Thus, RhlE can replace
      the function of RhlB in vitro. The results in the accompanying article show that
      CsdA can also replace RhlB in vitro. Thus, RhlB, RhlE and CsdA are
      interchangeable in in vitro RNA degradation assays.

PMID- 15554980
TI  - Two discrete elements are required for the replication of a repABC plasmid: an
      antisense RNA and a stem-loop structure.
AB  - The repABC replicons contain an operon encoding the initiator protein (RepC) and
      partitioning proteins (RepA and RepB). The latter two proteins negatively
      regulate the transcription of the operon. In this article we have identified two
      novel regulatory elements, located within the conserved repB-repC intergenic
      sequence, which negatively modulate the expression of repC, in plasmid p42d of
      Rhizobium etli. One of them is a small antisense RNA and the other is a stem-loop
      structure in the repABC mRNA that occludes the Shine-Dalgarno sequence of repC.
      According to in vivo and in vitro analyses, the small antisense RNA (57-59 nt)
      resembles canonical negative regulators of replication because: (i) it is
      transcribed from a strong constitutive promoter (P2), (ii) the transcript
      overlaps untranslated region upstream of the RepC coding sequences, (iii) the RNA
      forms one secondary structure acting as a rho-independent terminator, (iv) the
      antisense RNA is a strong trans-incompatibility factor and (v) its presence
      reduces the level of repC expression. Surprisingly, both of these seemingly
      negative regulators are required for efficient plasmid replication.

PMID- 15554981
TI  - Clp ATPases are required for stress tolerance, intracellular replication and
      biofilm formation in Staphylococcus aureus.
AB  - The Hsp100/Clp ATPases constitute a family of closely related proteins of which
      some members function solely as chaperones whereas others additionally can
      associate with the unrelated ClpP peptidase forming a Clp proteolytic complex. We
      have investigated the role of four Clp ATPases in the versatile pathogen,
      Staphylococcus aureus. Previously, we showed that ClpX is required for expression
      of major virulence factors and for virulence of S. aureus, but not for survival
      during heat shock. In the present study, we have inactivated clpC, clpB and clpL
      and, while none of these mutations affected toxin production, both ClpC and ClpB
      and to a minor extent ClpL were required for intracellular multiplication within
      bovine mammary epithelial cells. These defects were paralleled by an inability of
      the clpC mutant to grow at high temperature and of the clpB mutant to induce
      thermotolerance indicating that the protective functions of these proteins are
      required both at high temperature and during infection. By primer extension
      analysis and footprint studies, we show that expression of clpC and clpB is
      controlled by the negative heat-shock regulator, CtsR, and that ClpC is required
      for its repressor activity. Thus, ClpC is a likely sensor of stress encountered
      during both environmental stress and infection. In addition to virulence factor
      production the ability to form biofilms is of importance to S. aureus as a
      nosocomial pathogen. Interestingly, biofilm formation was reduced in the absence
      of ClpX or ClpC whereas it was enhanced in the absence of ClpP. Thus, our data
      show that Clp proteolytic complexes and the Clp ATPases control several key
      processes of importance to the success of S. aureus as a pathogen.

PMID- 15554982
TI  - The science and politics of propofol.
AB  - Propofol use for endoscopy is increasing rapidly. Its administration by
      registered nurses under the supervision of endoscopists has thus far proven safe,
      but is not realistically feasible in most U.S. endoscopy units. Therefore,
      propofol in the United States is being administered almost entirely by
      anesthetists. Transition to anesthetist-delivered sedation for endoscopy is being
      accompanied by increased costs, which in turn has the potential to adversely
      affect endoscopic practice. The gastroenterology and anesthesia communities
      should work together to explore mechanisms to expand propofol use or an
      alternative for endoscopy in a safe and cost-effective manner.

PMID- 15554983
TI  - Evidence based medicine (EBM) in practice: applying relative risk and relative
      risk reduction.

PMID- 15554984
TI  - The most important maneuver during colonoscopy.

PMID- 15554985
TI  - Pathophysiology of gastroesophageal reflux diseases in Chinese--role of transient
      lower esophageal sphincter relaxation and esophageal motor dysfunction.
AB  - BACKGROUND AND AIMS: Transient lower esophageal sphincter relaxation (TLESR) is
      the major mechanism for gastroesophageal reflux in the Western population. The
      major reflux mechanism in Chinese patients with GERD has not been studied before.
      METHODS: Fifty-four patients with GERD and 28 controls underwent stationary
      baseline manometry and the 24-h ambulatory esophageal pH monitoring. TLESRs were
      measured before and after an 850 kcal meal in the supine position. Primary
      peristalsis, secondary peristalsis, and esophageal acid clearance were measured
      by esophageal manometry. RESULTS: Total time esophageal pH </= 4 (7.3 vs 1.5, p=
      0.001) was significantly higher in patients with GERD when compared to controls.
      Majority of acid reflux episodes was due to TLESR in both patients with GERD and
      controls. The frequency of TLESRs after meal was similar between patients with
      GERD and controls (1.0 vs 1.3/h, p= 0.34). There was no difference in the
      distribution of reflux mechanism between patients with GERD and controls.
      However, patients with GERD had a significantly lower successful primary
      peristalsis (59%vs 70%, p= 0.043) when compared to controls. CONCLUSION: The
      frequency of TLESRs was similar between patients with GERD and controls during
      stationary manometry. Primary peristalsis was impaired in Chinese patients with
      GERD. Esophageal motor dysfunction may contribute to the pathophysiology of GERD
      in the Chinese population.

PMID- 15554986
TI  - Pathophysiology of GERD in China: the same factors at a lower scale.
AB  - Most of the factors involved in the pathogenesis of gastroesophageal reflux
      disease (GERD), previously described in European, Australian, and American
      studies, are present in Chinese patients with GERD, but at a lower scale. The
      acidity of gastric contents is reduced either spontaneously or by Helicobater
      pylori infection. A low-fat diet probably contributes to a more favorable gastric
      distribution of the meals, reduced obesity, and lowers the number of TLESRs. The
      prevalence of hiatal hernia is low and esophageal motility disorders are
      moderate. Like in Western countries, the pathophysiology of GERD in China is
      multifactorial, with variable combination of moderate abnormalities in individual
      patients, leading to milder forms of GERD.

PMID- 15554987
TI  - The role of gastric and duodenal agents in laryngeal injury: an experimental
      canine model.
AB  - BACKGROUND AND AIMS: The specific agents responsible for producing laryngeal
      signs and symptoms are currently unknown. We systematically evaluated the
      damaging role of gastric (acid and pepsin) and duodenal (bile acids and trypsin)
      ingredients individually and in combination on different laryngeal structures in
      an experimental canine model. METHODS: A total of 42 beagles were studied (wt 9
      15 kg each). After pentathol anesthesia all dogs underwent laryngoscopy. Injury
      (punch biopsy) was caused to the right vocal cord, medial arytenoid wall, and
      posterior cricoid wall on day 1. Pepsin (0.5 mg/ml), conjugated bile acid (CBA)
      (ursodeoxycholic acid, 300 micromolar), unconjugated bile acids (UBA) (cholic,
      300 micromolar), trypsin (0.5 mg/ml) at pH 1-2, 4-5, and 6-7 were applied
      bilaterally to laryngeal sites three times per week for a total of 9-12
      applications. Changes in laryngeal sites were scored visually. All dogs were
      sacrificed 1 day post last application. Laryngeal tissue was harvested and sent
      for blinded pathological examination. Histologic and visual scores were compared
      to each other and to control- and sham-treated dogs. RESULTS: Pepsin alone (8.5
      +/- 1.66) or combined with CBA (16.63 +/- 1.66) at pH 1-2 resulted in significant
      (p < 0.001) severe histological inflammation much greater than with other agents.
      Duodenal ingredients caused no or minimal degree of histological damage at all pH
      values. Visual scores above subtle erythema were significantly (p < 0.001) higher
      in the animals exposed to pepsin followed by CBA alone or in combination with
      pepsin at pH 1-2. There was a significant (p < 0.01) correlation between
      histology and visual scores (rho = 0.47; 95% CI = 0.30-0.60) for all sites
      combined. Of the three laryngeal sites, vocal cords were the most sensitive to
      injury by applied solutions. CONCLUSIONS: (i) In acidic refluxate, pepsin and
      CBAs are the most injurious agents affecting laryngeal tissue. (ii) Duodenal
      agents do not play a significant role in causing laryngeal injury. (iii)
      Aggressive acid suppression should eliminate the injurious potential of any
      gastroduodenal refluxate.

PMID- 15554988
TI  - Identification of Barrett's esophagus in relatives by endoscopic screening.
AB  - AIM: Familial aggregation of Barrett's esophagus and its associated cancers has
      been termed familial Barrett's esophagus (FBE). The aim of the study was to
      determine whether endoscopic screening would identify Barrett's esophagus (BE) in
      relatives of probands with BE or esophageal adenocarcinoma (EAC). METHODS: All
      living first-degree relatives of patients with long segment BE or EAC presenting
      to the endoscopy suite of two academic hospitals were sent validated
      questionnaires inquiring about gastroesophageal reflux symptoms and prior
      endoscopic evaluation. First-degree relatives of affected probands or affected
      relatives who reported no prior upper endoscopy were offered screening unsedated
      esophagoscopy. Relatives with chronic gastroesophageal reflux symptoms were also
      offered an alternative of conventional sedated upper endoscopy. The yield of
      screening endoscopy was measured. Screening endoscopy findings were then compared
      between family members of known FBE patients and those with "isolated" disease.
      RESULTS: One hundred and ninety-eight relatives from 69 families, 23 known FBE
      probands and 46 probands with apparently "isolated" disease, were enrolled. Forty
      relatives (29 FBE relatives and 11 relatives of probands with "isolated" disease)
      reported prior upper endoscopy. Screening upper endoscopies performed on 62 (25
      FBE and 37 "isolated" disease relatives) of the remaining 158 relatives
      identified Barrett's epithelium in 13 (21%). Compared to probands with apparently
      "isolated" disease, Barrett's epithelium (EAC, BE, or SSBE) was identified
      significantly more often in siblings and offspring of FBE probands, p</= 0.05.
      Endoscopic screening of relatives of FBE probands identified a multigeneration
      multiplex FBE pedigree consistent with an autosomally dominant inherited trait.
      Endoscopic screening of relatives of probands with reported "isolated" diseased
      did not identify any new FBE pedigrees. CONCLUSIONS: Endoscopy identified EAC,
      long-segment BE, and short-segment BE in a substantial proportion of first-degree
      relatives of affected members of FBE families. A familial susceptibility to
      develop Barrett's epithelium appears to be present in a subset of patients with
      BE and EAC.

PMID- 15554989
TI  - Is esophageal pH monitoring used appropriately in an open-access system? A
      prospective multicenter study.
AB  - OBJECTIVES: To evaluate the referral patterns and indications for esophageal pH
      monitoring in an open-access system and to determine whether these indications
      conform to practice guidelines of the American Gastroenterological Association
      (AGA). METHODS: A total of 851 consecutive patients referred for ambulatory pH
      monitoring to nine open-access gastrointestinal units over a 12-month period
      received a structured interview. The indication for the examination was decided
      by the physician performing the procedure, on the basis of the patient's clinical
      history and main complaint. RESULTS: Three hundred and twenty-three (38%)
      examinations were for indications in accordance with the guidelines. The
      proportion of appropriate requests in each center ranged from 34% to 47%. This
      figure was not significantly different in larger gastrointestinal units (more
      than 150 examinations per year) and smaller ones (35% and 40%; p= 0.14). The
      proportion of appropriate requests was 45% for gastroenterologists, 38% for
      surgeons, 32% for other specialists, and 24% for primary care physicians (PCPs)
      (p < 0.001). The percentage of appropriateness was significantly different
      between gastrointestinal specialists and PCPs (p < 0.001 vs gastroenterologists,
      p= 0.015 vs GI surgeons), and between gastroenterologists and other specialists
      (p= 0.006). The underuse of an empirical trial of acid-suppression therapy in
      patients with suspected reflux disease and the overuse of this test to confirm a
      diagnosis in patients with erosive esophagitis and in endoscopy-negative cases
      with typical symptoms responding completely to antisecretory therapy accounted
      for most of the referrals, which was not in accordance with the guidelines.
      CONCLUSIONS: In an open-access system, a high proportion of esophageal pH studies
      are done for indications not consistent with published guidelines, particularly
      among the examinations not requested by gastrointestinal specialists. Further
      education is still needed on the appropriate use of esophageal pH monitoring and
      management of gastroesophageal reflux disease (GERD).

PMID- 15554990
TI  - Effect of Helicobacter pylori infection on ghrelin expression in human gastric
      mucosa.
AB  - OBJECTIVES: One of the counter-effects of Helicobacter pylori eradication therapy
      is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing
      peptide. This endogenous secretagogue increases appetite and facilitates fat
      storage. The majority of circulating ghrelin is produced in the gastric mucosa.
      Therefore, we aimed at investigating changes in ghrelin immunoreactivity in
      gastric mucosa tissues of patients infected with H. pylori. METHODS: Sixty-one
      patients with H. pylori infection (25 cases each of duodenal and gastric ulcer,
      and 11 cases of gastritis) and 22 healthy controls without H. pylori infection
      were included in the study. H. pylori-infected patients received standard proton
      pump-based triple therapy followed by histological examination and (13)C-urea
      breath test to confirm H. pylori eradication. H. pylori was eradicated in 50 out
      of 61 patients. Biopsy specimens were obtained from antrum and corpus before and
      3 months following eradication. Ghrelin expression was evaluated
      immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin
      positive cells determined per 1 mm(2) of the lamina propria mucosa. RESULTS:
      There was no relationship between ghrelin immunoreactivity and body weight or
      body mass index for healthy controls. The number of ghrelin-positive cells was
      significantly lower for H. pylori-infected patients than for healthy controls.
      However, the ghrelin-positive cell number increased significantly following H.
      pylori eradication without significant change in severity of atrophy.
      CONCLUSIONS: These data indicated that H. pylori infection affected ghrelin
      expression. After H. pylori eradication, gastric tissue ghrelin concentration
      increased significantly. This could lead to the increased appetite and weight
      gain seen following H. pylori eradication.

PMID- 15554991
TI  - Comparison between the two systems to evaluate the appropriateness of endoscopy
      of the upper digestive tract.
AB  - OBJECTIVES: The aim of this study was to compare the diagnostic performance of
      the two systems for the evaluation of the appropriateness of upper digestive
      endoscopy suggested by the American Society of Gastrointestinal Endoscopy (ASGE)
      and by the European Panel on the Appropriateness of Gastrointestinal Endoscopy
      (EPAGE). METHODS: Patients referred for the upper digestive endoscopy (EGD) to a
      University Outpatients Clinic of Northeastern Italy were consecutively included
      in this prospective observational study. Before the EGD, the endoscopist assigned
      the patients to one of the ASGE appropriateness classes; another endoscopist then
      identified the detailed clinical scenario for the patients, which corresponds to
      scenarios examined by EPAGE by using a nine-point scale: 1-3 inappropriate; 4-6
      uncertain; and 7-9 appropriate. The relationship between the appropriateness of
      use and the presence of relevant endoscopic lesions (neoplasms, ulcers,
      esophagitis, erosive gastritis/duodenitis, stenosis, and varices) was assessed,
      calculating the sensitivity and the specificity for each of the ASGE criteria,
      and each of the EPAGE scores, and plotting them to form a receiver operating
      characteristic (ROC) curve. The area under the ROC curve (AUC) provides a summary
      measure of test performance, and can vary from a minimum of 0.5 to a maximum of
      1.0. We compared the AUC of the ROC curve derived from the ASGE criteria against
      that derived from the EPAGE criteria. RESULTS: A total of 2,300 consecutive
      patients were included in the study (42% men; mean age: 57.3; range: 12-99);
      comparison of appropriateness criteria according to the ASGE and EPAGE could be
      made for 2,000 patients. The AUC of the ROC curve derived from the ASGE criteria
      was 0.553 (95% CI: 0.527-0.579), significantly higher than the AUC of the ROC
      curve derived from the EPAGE score: 0.523 (95% CI: 0.497-0.549; p < 0.05).
      CONCLUSIONS: We suggest that the diagnostic yield for relevant endoscopic
      findings obtained by both the systems (ASGE and EPAGE) is low; slightly better
      results could be accomplished by the ASGE criteria.

PMID- 15554992
TI  - Clinical guidelines: the blind leading the deaf?
AB  - Clinical guidelines are developed by most specialist societies but the available
      data suggest that their impact on physician behavior is limited. National
      guidelines may need modification at the local level to account for local
      conditions and need regular updates to ensure that they continue to be based on
      the best available evidence. Measures to involve community practitioners in
      guideline development may enhance their uptake in the community.

PMID- 15554993
TI  - 170 degrees wide-angle colonoscope: effect on efficiency and miss rates.
AB  - BACKGROUND: Small polyps are routinely missed during colonoscopy even with
      careful examination. AIM: To determine and compare endoscopic efficiency and
      polyp miss rate between a prototype 170 degrees wide-angle (WA) colonoscope and a
      standard (S) colonoscope. METHODS: Two consecutive same-day colonoscopies were
      performed in 50 patients with intact colons. The patients were randomized to
      undergo the first colonoscopy with either the prototype WA 170 degrees angle of
      view colonoscope or an S adult 140 degrees angle of view colonoscope. RESULTS:
      The mean time for insertion was 2.09 (1.09) min versus 2.53 (1.47) min (p= 0.002)
      for the WA colonoscope and the S colonoscope, respectively. Similarly, the mean
      time for examination during withdrawal was shorter with the WA colonoscope (4.98
      (0.94) vs 5.74 (1.12) min; p < 0.0001). The mean insertion time for the second
      examination was shorter than the insertion time for the first examination,
      irrespective of the colonoscope (p= 0.006). However, the withdrawal times were
      not significantly different between the first and second examinations (p= 0.11).
      The miss rate for all polyps with the WA colonoscope (19%) was similar to the
      miss rate with the S colonoscope (27%; p= 0.19). The miss rates for adenomas with
      the WA (10/33; 30.3%) and the S scope (15/50; 30%) were similar (p= 0.98).
      CONCLUSIONS: The use of the WA colonoscope was associated with a reduction in
      insertion time to the cecum, as well as examination time during withdrawal. No
      evidence was found that the accuracy of the two colonoscopes differs.

PMID- 15554994
TI  - Antimitochondrial antibodies and reactivity to N. aromaticivorans proteins in
      Icelandic patients with primary biliary cirrhosis and their relatives.
AB  - OBJECTIVES: Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic
      disease of unknown etiology characterized by serum antimitochondrial antibodies
      (AMA) directed against a functionally related family of mitochondrial enzymes. We
      recently suggested that N. aromaticivorans might be the trigger of autoimmunity
      in PBC. No data are available on the specificity and crossreactivity of AMA in a
      genetically homogenous group of patients, such as the Icelandic population.
      METHODS: To address these issues and to confirm previous findings in a unique
      population, we obtained sera from 14 PBC patients and 85 first-degree relatives,
      all of Icelandic descent. We analyzed such sera for AMA specificity using
      recombinant mitochondrial antigens and for reactivity against N. aromaticivorans
      proteins. RESULTS: Thirteen of the 14 Icelandic patients with PBC (93%) were
      found AMA positive. We found that 5/13 AMA positive sera (38%) reacted against
      PDC-E2 only; 5/13 (or 38%) reacted against BCOADC-E2; and 2/13 (15%) reacted
      against all three antigens. There was no reactivity against OGDC-E2. Reactivities
      of patients' sera against N. aromaticivorans were consistent with the AMA status.
      One serum among the 85 first-degree relatives (1.2%) was found to be AMA
      positive, as well as reactive against N. aromaticivorans. CONCLUSIONS:
      Interestingly, despite the homogenous genetic background, the group of Icelandic
      patients with PBC was heterogeneous in their AMA reactive patterns and also
      reacted with N. aromaticivorans proteins.

PMID- 15554995
TI  - Novosphingobium aromaticivorans: a potential initiator of primary biliary
      cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is characterized by a T-cell-mediated destruction
      of bile duct epithelial cells that line the small intrahepatic bile ducts. The
      targets of activated T-lymphocytes are the dihydrolipoamide acetyltransferase
      components of the 2 oxo acid dehydrogenases, enzyme complexes that are important
      in oxidative energy metabolism. Pyruvate dehydrogenase is the best known of
      these. Its dihydrolipoamide acetyltransferase component is referred to as PDC-E2.
      A major question in understanding the pathogenesis of PBC is why PBC patients
      lose their tolerance to antigens that are found in virtually every cell in the
      body. A possible cause is molecular mimicry between microbial agents and self
      antigens. Infection with or exposure to a microorganism whose PDC-E2 bears close
      homology with human PDC-E2 could act as an immunological trigger that initiates
      the development of PBC. Emerging data suggest that there is a microorganism that
      may initiate the onset of PBC. Novosphingobium aromaticivorans is a gram negative
      strictly aerobic bacteria that is found worldwide in soil, water, and coastal
      plain sediments. Its PDC-E2-like proteins have a higher degree of homology with
      the immunodominant region of human PDC-E2 than any microorganism thus far studied
      (100-1,000 times greater than that of Escherichia coli). In addition, N.
      aromaticivorans can metabolize xenobiotics that are similar to the chemical
      compounds that react with sera from PBC patients. Some of these xenobiotics are
      immunologically related to lipoic acid, the cofactor that is at the active center
      of PDC-E2. Thus, N. aromaticivorans can theoretically break down self-tolerance
      in two ways: by molecular mimicry due to subclinical infection and by the
      metabolism of xenobiotics that are present in the environment. In an initial
      study, investigators found that antibodies against N. aromaticivorans were found
      in 77 of 77 PBC patients from Milan, Italy, who had antibodies to PDC-E2 and that
      the titers to N. aromaticivorans proteins were similar to those to human PDC-E2.
      The report in this issue of The American Journal of Gastroenterology confirms
      these earlier findings and demonstrates that exposure to N. aromaticivorans
      occurs in genetically different PBC patients from other regions. Thirteen of 14
      Icelandic PBC patients who were AMA positive reacted against at least one of the
      2 oxo acid dehydrogenase-E2 complexes. These observations provide additional
      evidence that exposure to N. aromaticivorans may trigger the development of PBC.

PMID- 15554996
TI  - Serum immunological profile in patients with chronic autoimmune cholestasis.
AB  - AIM: To compare patients who had biochemical and histological features of chronic
      autoimmune cholestasis (CAIC) using serological autoantibody profiling. METHODS:
      Patients (n = 174 CAIC; 79 AMA(-) and 95 AMA(+)) were profiled for the following
      antibodies: antinuclear antibodies (ANAs), antimitochondrial antibodies (AMAs),
      antismooth muscle actin (SMA, mainly F-actin), antiperinuclear cytoplasmic
      neutrophil antibodies (pANCAs), anti-SP100, anti-GP210, anti-M2 (2-oxo-acid
      dehydrogenase complexes), and antisoluble liver antigen (SLA). Liver specimens
      were reviewed according to staging, biliary interface activity, lobular
      hepatitis, granulomas, cholestasis, and florid ductal lesion. RESULTS: In
      patients who were AMA(-) by indirect immunofluorescence (IIF), 34.6% were
      positive for anti-M2 by immunoblotting. In 49 definitively AMA(-) patients, 24
      (48.9%) showed ANA-primary biliary cirrhosis (PBC)-related antibodies (rim-like,
      multiple nuclear dots, anti-SP100, or anti-GP210). There were no differences in
      immunological, biochemical, or histopathological features between IIF-AMA(+)
      patients and AMA(-) patients with anti-M2 or ANA-PBC-related antibodies. AIH
      related autoantibodies were found in 13 patients (7.5%). Patients with AMAs or
      ANA-PBC-related antibodies had higher IgM levels, whereas patients with
      antibodies highly specific for AIH had higher AST, bilirubin, and IgG levels, and
      AIH scores, and higher grades of lobular hepatitis. Overall, three distinct
      categories of patients were observed: AMA(+) or AMA(-) patients with ANA-PBC
      related antibodies; AMA(-) patients with non-PBC-related ANAs; and patients with
      AIH-related antibodies together with serum PBC markers. CONCLUSION: Since these
      three groups had immunological, biochemical, and histopathological differences,
      they ought to be considered as separate clinical subentities rather than as
      merely AMA(-) or AMA(+) patients with autoimmune cholestasis.

PMID- 15554997
TI  - Outcomes of patients with hepatocellular carcinoma presenting with variceal
      bleeding.
AB  - OBJECTIVE: Variceal bleeding is an important manifestation of hepatocellular
      carcinoma (HCC). However, little has been documented in the literature regarding
      the outcomes of HCC patients presenting with variceal bleeding. This study
      evaluated the clinical characteristics, management, and outcomes of this specific
      group of patients. METHODS: A retrospective analysis of a prospectively collected
      database comprising 2,928 HCC patients managed from January 1989 to December 2002
      identified 78 patients who had presented with variceal bleeding. Their clinical
      outcomes were compared to those patients who did not present with variceal
      bleeding, and a multivariate analysis was performed to identify prognostic
      factors for their survival. RESULTS: HCC patients who presented with variceal
      bleeding had more severe cirrhosis than those who did not, with a significantly
      higher serum bilirubin level, lower albumin level, lower platelet count, and
      longer prothrombin time. They had significantly smaller HCCs but more frequent
      portal vein thrombosis. There was a significant difference in the overall
      survival between HCC patients who presented with variceal bleeding and those who
      did not (median 3.5 months vs 7.5 months, p < 0.001). In the variceal bleeding
      group, by multivariate analysis, treatment with transarterial chemoembolization
      was the only significant independent prognostic factor for survival (odds ratio
      17.16, 95% CI: 2.81-104.91, p= 0.002). CONCLUSIONS: HCC patients who presented
      with variceal bleeding can be expected to have a significantly worse survival
      outcome than the general HCC patients. However, transarterial chemoembolization
      may offer some survival benefit to a selected group of HCC patients presenting
      with variceal bleeding.

PMID- 15554998
TI  - The Amerindian's genes in the Mexican population are associated with development
      of gallstone disease.
AB  - BACKGROUND: It has been suggested that genes related to Amerindian ancestry
      account for the high prevalence of gallstone disease (GD) observed in Mexican
      Americans. The HLA-B39 is an allele found in higher frequency in Amerindians
      whereas HLA-B15 is rarely found. The aim of this study was to test the hypothesis
      that gallstone susceptibility genes are more prevalent in Mexicans with recent
      Amerindian ancestry. METHODS: We carried out a prospective case-controlled study.
      Subjects were divided into those who had stones visible on gallbladder ultrasound
      (cases), and those whose ultrasounds were negative for gallstones (controls).
      Body mass index (BMI) was calculated, and serum lipids and lipoprotein, and
      glucose levels were measured. Class I HLA (HLA-B) typing was performed by PCR
      amplification of genomic DNA. RESULTS: Of the 1,101 subjects, 146 were classified
      as subjects with GD (cases) and 955 as subjects without GD (controls). Mean age
      of the cases was 53.5 +/- 12.5 yr versus 44.78 +/- 12.0 yr for the controls, p=
      0.001. A family history of GD was observed in 48% of the cases versus 28.4% of
      the controls, p= 0.001. HLA-B39 was more frequently increased in GD subjects
      (0.162), compared with controls (0.063), p= 0.008. The odds ratio of having HLA
      B39 was 2.8 and 95% (CI 95%= 1.3-6.3) for GD; HLA-B15 was more frequently
      increased in controls than in cases. CONCLUSIONS: The most prevalent HLA alleles
      detected in these GD cases are characteristic of Amerindian populations,
      supporting the role of genetics in the high prevalence of the development of GD
      in Mexican mestizos.

PMID- 15554999
TI  - Videocapsule endoscopy versus barium contrast studies for the diagnosis of
      Crohn's disease recurrence involving the small intestine.
AB  - OBJECTIVES: Historically, suspected Crohn's disease (CD) has been evaluated with
      small bowel follow-through (SBFT) or enteroclysis (equally accurate). This study
      was undertaken to determine the accuracy of videocapsule endoscopy (VCE) in the
      diagnosis of CD relative to SBFT and clinical/laboratory indices of CD activity.
      Previous investigations have used VCE for the diagnosis of suspected CD in
      patients presenting with a variety of gastrointestinal symptoms. This is the
      first study to evaluate the occurrence of active disease in patients with known
      CD. METHODS: Thirty subjects (22 female, 8 male, aged 36.9 +/- 14.2 yr); all with
      prior CD diagnosis made on the basis of standard criteria (5.5 +/- 6.5 yr prior
      to study), in whom recurrent CD was suspected based on abdominal pain, diarrhea,
      anemia, and/or arthralgias. Subjects were studied in a prospective, blinded
      evaluation of VCE versus SBFT. SBFT was performed first; those with stricture and
      proximal bowel dilation were excluded from further study. For SBFT, studies were
      graded as grade 0 (normal), grade 1 (minimal nodularity, ulcerations, normal
      luminal diameter, < 5 cm involved), grade 2 (more extensive ulcers, minimal
      luminal narrowing, 5-10 cm involved), or grade 3 (fistula, skip areas, extensive
      ulceration, >10 cm involved). VCE was performed within 1 wk of SBFT. Serum was
      obtained for ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein),
      stool was obtained for alpha-1 antitrypsin, and the Harvey Bradshaw index of CD
      severity was calculated. VCE (digitalized video) was graded as grade 0 (normal),
      grade 1 (erythema, isolated villi loss), grade 2 (erosion, no ulcer), or grade 3
      (ulcers, spontaneous bleeding, and/or stricture). RESULTS: Twelve patients were
      excluded for small bowel obstruction. VCE and SBFT scores highly correlated (r =
      0.65; p= 0.001). Active CD was visualized in 21 of 30 patients with videocapsule
      endoscopy and in 20 of 30 patients with SBFT. Complete agreement occurred in 13
      of 30 studies; 13 of 17 studies differed by one grade. SBFT found mucosal disease
      in 20 of 30 patients and VCE found mucosal disease in 21 of 30 patients. VCE
      found mucosal disease in 6 patients (5 in grade 1, 1 in grade 3) with normal
      SBFT. SBFT showed CD in 5 patients (all grade 1) with normal VCE. Neither VCE nor
      SBFT scores correlated with biological or clinical indices. Patient satisfaction
      was superior for VCE. CONCLUSIONS: VCE and SBFT are complementary for the
      diagnosis of CD. SBFT may be required to detect strictures as the videocapsule
      may not pass. However, some strictures may also be missed with SBFT. VCE is less
      invasive, less time-consuming for the patient than SBFT, and avoids radiation
      exposure, although reading time is greater for the gastroenterologist than the
      radiologist. Given that patients with clinically suspected CD recurrence may not
      have active disease, unnecessary and potentially harmful empiric therapy is not
      warranted without imaging.

PMID- 15555000
TI  - Vitamin K status in patients with Crohn's disease and relationship to bone
      turnover.
AB  - BACKGROUND: There is a high prevalence of osteopenia among patients with Crohn's
      disease (CD). There is some evidence that a deficiency of certain bone-active
      nutrients (including vitamins K and D) may have a partial role in this bone loss.
      AIMS: To compare the intake and the status of vitamin K in CD patients, currently
      in remission, with age- and sex-matched controls, and furthermore to investigate
      the relationship between vitamin K status and bone turnover in these patients.
      SUBJECTS: CD patients (n = 44; mean age: 36.9 yr) and matched controls (n = 44)
      were recruited from the Cork University Hospital and Cork City area,
      respectively. METHODS: Bloods were analyzed for the total and undercarboxylated
      (Glu)-osteocalcin and urine analyzed for cross-linked N-telopeptides of type I
      collagen (NTx). Vitamin K(1) intake was estimated by food frequency
      questionnaire. RESULTS: Vitamin K(1) intake in CD patients tended to be lower
      than that of controls (mean (SD), 117 (82) vs 148 (80) mug/d, respectively; p=
      0.059). Glu and NTx concentrations in CD patients were higher than controls (mean
      (SD), 5.1 (3.1) vs 3.9 (2.1) ng/ml, respectively; p= 0.03 for Glu; and 49 (41) vs
      25.8 (19.5) nM BCE/mM creatinine, respectively; p= 0.001 for NTx). In CD
      patients, Glu was significantly correlated with NTx (r= 0.488; p < 0.001), even
      after controlling for age, gender, vitamin D status, calcium intake, and
      corticosteroid use. CONCLUSION: Vitamin K status of CD patients was lower than
      that of the healthy controls. Furthermore, the rate of bone resorption in the CD
      was inversely correlated with vitamin K status, suggesting that it might be
      another etiological factor for CD-related osteopenia.

PMID- 15555001
TI  - A prospective comparative study of ASCA and pANCA in Chinese and Caucasian IBD
      patients.
AB  - BACKGROUND: Inflammatory bowel disease manifests throughout all ethnic groups.
      Antisaccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies
      (pANCA) can aid in the differentiation between Crohn's disease (CD) and
      ulcerative colitis (UC), but their sensitivity may vary between races.
      OBJECTIVES: This study compared the sensitivity, specificity, and positive and
      negative predictive values (PPV, NPV) of pANCA and ASCA between Chinese and
      Caucasian IBD populations and identified disease subtype associations. RESULTS:
      Three hundred patients were prospectively recruited from Caucasian and Chinese
      populations (CD, n = 50, UC, n = 50, controls, n = 50 each). pANCA detection was
      greater in Caucasian than Chinese UC patients (p= 0.046). ASCA IgG detection was
      similar, but IgA was lower in Chinese CD patients (p < 0.001). Differentiation
      between UC and CD (+ve pANCA/-ve ASCA) demonstrated a PPV of 92% in isolated
      colonic disease. Logistic regression in CD identified positive pANCA had a lower
      association with ileal (OR = 6.8, p= 0.0067) and complicated disease (OR = 5.5,
      p= 0.015). Caucasian CD patients with positive ASCA IgA/IgG had a greater
      association with ileal (OR = 6.7, p= 0.022) or complicated disease (OR = 9.4, p=
      0.0073) and in Chinese CD patients positive ASCA IgA/IgG was associated with
      isolated ileal disease (OR = 16.8, p= 0.032). Linear regression demonstrated that
      higher ASCA titers predicted complicated CD and isolated ileal disease.
      CONCLUSIONS: This study identified that pANCA is more sensitive in Caucasian than
      Chinese UC and that ASCA IgA has a low yield in Chinese CD. pANCA and ASCA are
      useful for differentiating between UC and CD in both populations, and ASCA IgG
      and IgA titers have potential use in determining the risk of developing
      complicated CD.

PMID- 15555002
TI  - Long-term safety and efficacy of alosetron in women with severe diarrhea
      predominant irritable bowel syndrome.
AB  - OBJECTIVES: To assess long-term safety and efficacy of alosetron in women with
      severe, chronic diarrhea-predominant IBS and in a subset having more frequent
      urgency (i.e., bowel urgency at least 10 of 14 days during screening). METHODS:
      Randomized patients received either alosetron 1 mg (n = 351) or placebo (n = 363)
      twice daily during a 48-wk, double-blind study. The primary endpoint was the 48
      wk average rate of adequate relief of IBS pain and discomfort. Secondary
      endpoints included 48-wk average satisfactory control rates of urgency, stool
      frequency, stool consistency, and bloating. Other efficacy endpoints were average
      monthly adequate relief and urgency control rates and impact of provided rescue
      medication. RESULTS: Alosetron-treated patients had significantly greater 48-wk
      average adequate relief (p= 0.01) and urgency control (p < 0.001) rates,
      regardless of rescue medication use, compared with placebo. Results in subjects
      with more frequent urgency were more robust than those in the overall population
      (p= 0.005). In weeks without rescue medication use, satisfactory control rates
      for stool frequency and stool consistency were significantly greater in alosetron
      treated patients than placebo. Alosetron-treated patients had significantly
      greater adequate relief than placebo-treated patients (p < 0.05) in 9 of 12
      months and significantly greater urgency control (p < 0.001) in all months.
      Adequate relief and urgency control were maintained throughout the treatment.
      Adverse events and serious adverse events were similar between treatment groups,
      except for constipation. Neither ischemic colitis nor serious events related to
      bowel motor dysfunction was reported. CONCLUSIONS: Long-term use of alosetron is
      effective and well-tolerated in women with chronic, diarrhea-predominant IBS,
      including those with more frequent urgency.

PMID- 15555003
TI  - Investigation of the pathophysiology of fecal seepage.
AB  - BACKGROUND AND AIM: Unintentional seepage of stool without awareness is common
      but its pathophysiology is poorly understood. Our aim was to examine the
      underlying mechanism(s) for fecal seepage. METHODS: We evaluated prospectively 25
      patients with fecal seepage, by performing anorectal manometry, balloon
      expulsion, saline infusion, pudendal nerve latency tests, and symptom assessments
      and compared their data with 26 fecal incontinence patients and 43 healthy
      controls. RESULTS: Predisposing factors for fecal seepage were back injury (7),
      obstetric injury (6), hemorrhoidectomy (3), pelvic radiotherapy (1), and unknown
      (8). In the seepage group, the resting and squeeze sphincter pressures were lower
      (p < 0.02) than healthy controls, but higher (p < 0.002) than incontinent group.
      During straining, the intrarectal pressure and defecation index were lower (p <
      0.05) in the seepage group compared to controls; 72% showed dyssynergia and
      balloon expulsion time was prolonged (p < 0.01). Threshold for first rectal
      sensation was impaired (p < 0.002) in the seepage group compared to controls and
      incontinent group. The seepage group retained more (p < 0.001) saline than the
      incontinent group but pudendal nerve latency time was impaired (p < 0.05) in both
      patient groups compared to controls. CONCLUSIONS: Anal sphincter function and
      rectal reservoir capacity were relatively well preserved but most patients with
      seepage demonstrated dyssynergia with impaired rectal sensation and impaired
      balloon expulsion. Thus, incomplete evacuation of stool may play a significant
      role in the pathogenesis of seepage.

PMID- 15555004
TI  - The prevalence and risk factors of functional dyspepsia in a multiethnic
      population in the United States.
AB  - BACKGROUND AND AIMS: The prevalence of functional dyspepsia (FD) in the general
      population is not known. The aim of this study is to measure the prevalence of FD
      and its risk factors in a multiethnic volunteer sample of the U.S. population.
      METHODS: One thousand employees at the Houston VA Medical Center were targeted
      with a symptom questionnaire asking about upper abdominal symptoms, followed by a
      request to undergo endsocopy. Dyspepsia was defined by the presence of epigastric
      pain, fullness, nausea, or vomiting, and FD was defined as dyspepsia in the
      absence of esophageal erosions, gastric ulcers, or duodenal ulcers or erosions.
      The presence of dyspepsia and FD was examined in multiple logistic regression
      analyses. RESULTS: A total of 465 employees completed the relevant questions and
      of those 203 had endoscopic examination. The age-adjusted prevalence rate of
      dyspepsia was 31.9 per 100 (95% CI: 26.7-37.1), and 15.8 per 100 (95% CI: 9.6
      22.0) if participants with concomitant heartburn or acid regurgitation were
      excluded. Subjects with dyspepsia were more likely to report smoking, using
      antacids, aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), and consulting
      a physician for their symptoms (p < 0.05) than participants without dyspepsia.
      Most (64.5%) participants with dyspepsia who underwent endoscopy had FD. The age
      adjusted prevalence rate of FD was 29.2 per 100 (95% CI: 21.9-36.5), and 15.0 per
      100 (6.7-23.3) if subjects with GERD were excluded. Apart from a trend towards
      association with older age in the multiple regression analysis, there were no
      significant predictors of FD among participants with dyspepsia. CONCLUSIONS: Most
      subjects with dyspepsia have FD. The prevalence of FD is high but predictors of
      FD remain poorly defined.

PMID- 15555005
TI  - A prospective randomized trial comparing low-dose oral sodium phosphate plus
      stimulant laxatives with large volume polyethylene glycol solution for colon
      cleansing.
AB  - This study examined whether the combination of a single dose (45 ml) oral sodium
      phosphate (NaP), four bisacodyl tablets (5 mg), and one bisacodyl enema (10 mg)
      preparation, Fleet Prep Kit 3 (FPK #3), was better tolerated and more efficacious
      than 4 L polyethylene glycol solution (PEG) for colonic cleansing prior to
      colonoscopy. One hundred and seventy-one patients were enrolled in this
      prospective, randomized, single-blinded study designed to detect a 20% or greater
      difference in patient tolerance and effectiveness in colonic cleansing between
      the two agents. The single dose of NaP and the bisacodyl tablets were
      administered at 1900 h and at 2100 h, respectively, the evening prior to
      colonoscopy and the bisacodyl enema 2 h before the procedure. PEG was consumed
      over 1-2 h the evening prior to colonoscopy. Most patients (84%) found the FPK #3
      easy or tolerable compared to only 33% receiving PEG (p < 0.001). Over 40% could
      not complete the PEG. There was no detectable difference in the efficacy between
      the two preparations (p= 0.74). Comparison of biochemical and hemodynamic values
      obtained before and after colonic cleansing did not reveal any significant
      differences apart from hyperphosphatemia in a few patients (16%) receiving FPK #3
      and minor changes in blood urea nitrogen and chloride. These findings suggest
      that FPK #3 is better tolerated and as safe as PEG but does not provide more
      efficacious cleansing of the colon.

PMID- 15555006
TI  - A cost-minimization analysis of alternative strategies in diagnosing pancreatic
      cancer.
AB  - BACKGROUND: Several modalities currently exist for tissue confirmation of
      suspected pancreatic cancer prior to therapy. Since there is a paucity of cost
      minimization studies comparing these different biopsy modalities, we analyzed
      costs and examined effectiveness of four alternative strategies for diagnosing
      pancreatic cancer. METHODS: A decision analysis model of patients with suspected
      pancreatic cancer was constructed. We analyzed costs, failure rate, testing
      characteristics, and complication rates of four commonly employed diagnostic
      modalities: 1) computerized tomography or ultrasound-guided fine-needle
      aspiration (CT/US-FNA), 2) endoscopic retrograde cholangiopancreatography with
      brushings (ERCP-B), 3) Endoscopic ultrasound-guided fine-needle aspiration biopsy
      (EUS-FNA), and 4) laparoscopic surgical biopsy. If the first attempt with a
      particular modality failed, a different modality was employed to identify the
      most preferable secondary biopsy strategy. RESULTS: This analysis identifies EUS
      FNA as the preferred initial modality for the diagnosis of pancreatic cancer.
      Resultant expected costs and strategies in decreasing optimality include: 1) EUS
      FNA (1,405 dollars), 2) ERCP-B (1,432 dollars), 3) CT/US-FNA (3,682 dollars), and
      4) surgery (17,711 dollars). If a patient presents with obstructive jaundice,
      decision analysis modeling resulted in a total expected costs of 1,970 dollars if
      ERCP-B is successful at the time of biliary stent placement. Additional analyses
      to identify the preferred follow-up modality after a failed alternative method
      showed that EUS-FNA is the preferred secondary modality if any of the other three
      modalities failed first, in both the setting of and absence of obstructive
      jaundice. One- and two-way sensitivity analysis of the variables shows unchanged
      results over an acceptable range. CONCLUSIONS: This cost-minimization study
      illustrates that EUS-FNA is the best initial and the preferred secondary
      alternative method for the diagnosis of suspected pancreatic cancer. In addition
      to local expertise and availability, costs and diagnostic yield should be
      considered when choosing an optimal diagnostic strategy.

PMID- 15555007
TI  - Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults
      with Crohn's disease and ulcerative colitis: diagnostic value and correlation
      with disease phenotype.
AB  - OBJECTIVES: Serologic testing is increasingly being utilized to evaluate children
      with suspected inflammatory bowel disease (IBD). The aim of this paper was to
      evaluate the sensitivity and specificity of a currently available panel involving
      four antibodies: deoxyribonuclease (DNase)-sensitive perinuclear antineutrophil
      cytoplasmic antibody (DNase-sensitive pANCA), IgA and IgG antibodies to
      Saccharomyces cerevisiae (IgA and IgG ASCA), and antibody to Escherichia coli
      outer membrane porin (anti-OmpC). We also wished to determine whether antibody
      levels correlated with disease activity, and whether a specific antibody pattern
      correlated with location and outcome of disease in children. METHODS: We studied
      sera from 81 children with Crohn's disease (CD), 54 with ulcerative colitis (UC),
      and 63 controls. Clinical data, disease activity, and disease diagnosis were
      gathered at the time of serum sampling, and charts were re-reviewed at time of
      the study to determine long-term outcome. Enzyme-linked immunosorbent assay was
      utilized to determine titers of antibodies to ASCA, DNase-sensitive pANCA, and
      anti-OmpC; the presence of perinuclear staining for ANCA was confirmed by
      immunofluorescence. RESULTS: We identified ASCA antibodies in 44% of CD patients,
      0% of UC patients, and 1 control patient. DNase-sensitive pANCA antibodies were
      found in 70% of patients with UC, 18% of CD patients (predominantly Crohn's
      colitis), and 3% of controls. Anti-OmpC as an isolated assay had low sensitivity
      for both CD (24%) and UC (11%), and displayed a 5% false-positive rate. However,
      anti-OmpC did identify a small number of IBD patients not detected by the other
      assays. If any one or more of the four antibodies was positive, the overall
      sensitivity of the four antibody panel was 65% for CD and 76% for UC, with a
      specificity of 94%. Patients who were ASCA-positive were more likely to have
      disease of the ileum or ileum and right colon than patients who were ASCA
      negative (58%vs 18%, p < 0.001). Patients with ASCA-positive were also more
      likely to require ileocecal resection (36%vs 13%, p < 0.05). CONCLUSIONS: A
      currently available commercial antibody panel has good sensitivity and excellent
      specificity for CD and UC. The ASCA antibodies, while highly specific for CD,
      identify predominantly the subset of children with disease of the ileum and
      ascending colon who may be at increased risk of surgery.

PMID- 15555008
TI  - Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway.

PMID- 15555009
TI  - Pathogenesis of chronic pancreatitis: an evidence-based review of past theories
      and recent developments.
AB  - In the past several decades, four prominent theories of chronic pancreatitis
      pathogenesis have emerged: the toxic-metabolic theory, the oxidative stress
      hypothesis, the stone and duct obstruction theory, and the necrosis-fibrosis
      hypothesis. Although these traditional theories are formulated based on
      compelling scientific observations, substantial contradictory data also exist for
      each. Furthermore, the basic premises of some of these theories are directly
      contradictory. Because of the recent scientific progress in the underlying
      genetic, cellular, and molecular pathophysiology, there have been substantial
      advances in the understanding of chronic pancreatitis pathogenesis. This paper
      will provide an evidence-based review and critique of the traditional pathogenic
      theories, followed by a discussion of the new advances in pancreatic
      fibrogenesis. Moreover, we will discuss plausible pathogenic sequences applied to
      each of the known etiologies.

PMID- 15555010
TI  - Development of Barrett's esophagus six months after total gastrectomy.
AB  - Barrett's esophagus (BE) is an acquired disease of the esophagus, in which
      esophageal squamous epithelium is changed by injury from reflux to metaplastic
      intestinal type columnar epithelium. BE is the premalignant lesion of
      adenocarcinoma of the esophagus. It is widely accepted that the long-standing
      reflux of gastric acid is a catalyst for the development of BE. More recent work
      points toward the reflux of duodenal secretions as a catalyst in this disease
      process as well. Moreover, the time course for the development of BE once a
      patient has reflux is not known. Our case challenges the currently defined time
      course of "long-standing" reflux symptoms for the development of BE, and supports
      the role of duodenal secretions alone in the development of BE. A 68-yr-old
      Caucasian man was admitted with weight loss, left upper quadrant pain, a
      hemoglobin of 6.8, and heme-positive stool. Esophagogastroduodenoscopy (EGD)
      revealed normal esophageal mucosa and a mass in the gastric cardia. Biopsies
      showed moderately differentiated gastric adenocarcinoma. The patient underwent a
      total gastrectomy, distal esophagectomy, and a Roux-en-Y esophagojejunostomy.
      Pathology confirmed gastric adenocarcinoma (T1 N0 Mx). The distal esophagus and
      gastroesophageal junction in the resected specimen were grossly and
      microscopically normal. Six months later an EGD, prompted by new complaints of
      regurgitation and dyspepsia, revealed distal esophageal mucosa lined by red
      colored columnar tissue. Biopsies showed intestinal type epithelium. Thus, our
      case report's contribution to the current literature is twofold. It provides
      evidence of development of BE solely from duodenal reflux, and it documents a
      relatively short time span to development of BE.

PMID- 15555011
TI  - Treatment of achalasia: the role of laparoscopic cardiomyotomy needs to be
      emphasized.

PMID- 15555013
TI  - Reduction of serum HCV RNA titer by bezafibrate therapy in patients with chronic
      hepatitis C.

PMID- 15555014
TI  - Transient Budd-Chiari syndrome due to iatrogenic subcapsular fluid accumulation
      following thoracocentesis.

PMID- 15555015
TI  - Dominant strictures in patients with primary sclerosing cholangitis-revisited.

PMID- 15555016
TI  - Losartan in preascitic cirrhosis.

PMID- 15555019
TI  - A pioneer in psychotherapy research: Aaron Beck. Interview by Sidney Bloch.

PMID- 15555020
TI  - Australian and New Zealand clinical practice guidelines for the management of
      adult deliberate self-harm.
AB  - BACKGROUND: The Royal Australian and New Zealand College of Psychiatrists is co
      ordinating the development of clinical practice guidelines (CPGs) in psychiatry,
      funded under the National Mental Health Strategy (Australia) and the New Zealand
      Health Funding Authority. METHOD: For these guidelines, the CPG Team for
      Deliberate Self-harm reviewed the treatment outcome literature (including meta
      analyses) and consulted with practitioners and patients. TREATMENT
      RECOMMENDATIONS: (i) Organization of general hospital services to provide:
      emergency department admission; a safe environment; integrated medical and
      psychiatric management; risk assessment; identification of psychiatric morbidity,
      and adequate follow-up. (ii) Detection and treatment of any psychiatric disorder.
      (iii) Dialectical behaviour therapy, psychoanalytically orientated partial
      hospitalization or home-based interpersonal therapy (for certain patients) to
      reduce repetition of deliberate self-harm (DSH). CONCLUSION: Deliberate self-harm
      is common and is costly in terms of both individual distress and service
      provision. General hospitals are often the first point of clinical contact, but
      may not be appropriately organized to care for these patients. Evidence for the
      effectiveness of psychological treatments is based on single RCTs without
      replication. The three recommended psychological treatments are not widely
      available in Australia and New Zealand, and the interventions that are, such as
      cognitive behaviour therapy, problem solving and 'green cards' (an agreement
      guaranteeing access to services), do not reduce repetition of DSH. The effect of
      follow-up in psychiatric hospitals or in the community is poorly understood. We
      need to develop and evaluate interventions that will reduce repetition of both
      fatal and non-fatal deliberate self-harm and improve the person's functioning and
      quality of life.

PMID- 15555021
TI  - Critique of the guidelines for the treatment of depression: flaws in the
      construction.
AB  - OBJECTIVE: To examine the likely utility of the recently published Australian and
      New Zealand clinical practice guidelines for the treatment of depression. METHOD:
      The guidelines are critiqued for their intrinsic logic and their success in
      extracting potentially valid and useful management templates. RESULTS: This paper
      provides examples of key limitations to many specific interpretations and
      conclusions. CONCLUSIONS: It is argued that these guidelines are far less precise
      and informative for clinical practice than they appear and with a disturbing lack
      of rigour for a document promulgated by a professional college.

PMID- 15555022
TI  - Evidence-based guidelines: response to professor Gordon Parker's critique.
AB  - OBJECTIVE: To clarify the development of the 'Australian and New Zealand clinical
      practice guidelines for the treatment of depression' and to discuss the critique
      of these guidelines. METHOD: Consideration of international practice in evidence
      based medicine and rebuttal of criticisms. RESULTS: We agree with Professor
      Gordon Parker on fundamental issues in the treatment of depression. His main
      criticisms reflect his concerns about the classification of depression. We
      consider that many of his detailed criticisms reflect a difference of opinion on
      how data should be evaluated or interpreted. CONCLUSIONS: The guideline for the
      treatment of depression makes sound recommendations, in agreement with comparable
      guidelines from the US and the UK.

PMID- 15555023
TI  - Grey lungs and blue moods: smoking cessation in the context of lifetime
      depression history.
AB  - OBJECTIVE: To present an overview of the relationship between depression and
      cigarette smoking and to provide recommendations for clinicians who wish to help
      patients with a history of depression to stop smoking. METHOD: English language
      journal articles published in the last 15 years on clinical material related to
      depression history, smoking cessation and related health issues were collected
      via MEDLINE, PsycINFO and Cochrane Library database searches. RESULTS: Nicotine
      dependence is associated with increased rates of depression prior to and after
      taking up smoking as well as increased rates of suicidal ideation. Depression
      history is associated with increased rates of nicotine dependence, problems with
      smoking cessation and depression after cessation. While nicotine replacement and
      counselling are effective for smoking cessation, standard smoking cessation
      strategies may not pay sufficient attention to the needs of smokers with a
      depression history. Some antidepressants (bupropion and nortriptyline) are
      particularly effective for those with a lifetime depression history as they
      appear to assist with dysphoria during withdrawal and prevent relapse.
      Psychological and lifestyle strategies, such as motivational interviewing,
      relaxation exercises and mood charts, assist in mood regulation over and above
      the standard smoking cessation treatments for smokers with a depression history,
      who require more attention to relapse of depression and smoking after quitting.
      CONCLUSIONS: There is a complex and circular relationship between depression,
      smoking and medical illness that complicates smoking cessation in those who have
      a history of depression. Depression-history smokers require a multimodal approach
      to assist with mood regulation and nicotine withdrawal. Further research is
      required to identify effective strategies to reduce smoking in this context.

PMID- 15555024
TI  - Trauma-related dissociation: conceptual clarity lost and found.
AB  - OBJECTIVE: Imprecise conceptualizations of dissociation hinder understanding of
      trauma-related dissociation. An heuristic resolution for research and clinical
      practice is proposed. METHOD: Current conceptualizations of dissociation are
      critically examined. They are compared with a new theory that incorporates
      classical views on dissociation with other contemporary theories related to
      traumatization, viewing dissociation as a lack of integration among
      psychobiological systems that constitute personality, that is, as a structural
      dissociation of the personality. RESULTS: Most current views of dissociation are
      overinclusive and underinclusive. They embrace non-dissociative phenomena--rigid
      alterations in the level and field of consciousness--prevalent in non-traumatized
      populations, and which do not require structural dissociation. These views also
      largely disregard somatoform and positive symptoms of dissociation and
      underestimate integrative deficiencies, while emphasizing the psychological
      defensive function of dissociation. They do not offer a common psychobiological
      pathway for the spectrum of trauma-related disorders. Structural dissociation of
      the personality likely involves divisions among at least two psychobiological
      systems, each including a more or less distinct apperceptive centre, that is, a
      dissociative part of the personality. Three prototypical levels of structural
      dissociation are postulated to correlate with particular trauma-related
      disorders. CONCLUSIONS: Limitation of the concept of dissociation to structural
      dividedness of the personality sets it apart from related but non-dissociative
      phenomena and provides a taxonomy of dissociative symptoms. It postulates a
      common psychobiological pathway for all trauma-related disorders. Trauma-related
      dissociation is maintained by integrative deficits and phobic avoidance. This
      conceptualization advances diagnosis, classification, treatment and research of
      trauma-related disorders.

PMID- 15555025
TI  - Clozapine-related myocarditis and cardiomyopathy in an Australian metropolitan
      psychiatric service.
AB  - OBJECTIVES: Myocarditis and cardiomyopathy are rarely reported complications of
      clozapine treatment. The incidence of clozapine-related myocarditis has been
      variably reported at between 0.03% and 0.19% of initiations and cardiomyopathy
      has been reported even less commonly. In our Brisbane-based service, nine of 94
      patients initiated on clozapine over the previous 3 years appeared to have
      experienced myocarditis or cardiomyopathy. The unique co-location of our service
      with a major cardiothoracic hospital facilitated a review of identified cases to
      inform decisions regarding clozapine treatment and rechallenge in this service.
      METHOD: Cases were identified by survey of psychiatric and cardiac medical staff
      at The Prince Charles Hospital and subjected to re-evaluation by a
      multidiscipline consensus panel. The panel compared cases to international
      reports and identified the clinical features that supported a diagnosis of
      clozapine-related myocarditis or cardiomyopathy. RESULTS: This process resulted
      in the stratification of the nine cases into the following categories of
      diagnostic likelihood: three highly probable, three probable, and two possible
      cases of clozapine-related myocarditis, and one possible case of clozapine
      related cardiomyopathy. Successful clozapine rechallenge/continuation was
      undertaken in two patients and the panel agreed that this was a viable future
      option for several other patients. CONCLUSIONS: Findings of the panel review
      supported the initial clinical diagnoses. This confirmed that there was an
      apparent high incidence of clozapine-related myocarditis within this service, for
      which there was no clear reason. Mechanisms underlying clozapine-related
      myocarditis and cardiomyopathy, as well as successful clozapine continuation and
      rechallenge were considered, but definitive explanations remain unknown. This
      review highlighted the clinician's role in post-marketing drug surveillance to
      guide rational management of suspected adverse drug effects.

PMID- 15555026
TI  - Parenting programs for women with mental illness who have young children: a
      review.
AB  - OBJECTIVE: To provide an overview of the literature relevant to, and describing,
      parenting programs for women with mental illness who have young children. METHOD:
      A literature search was undertaken, including MEDLINE, PsycINFO, CINAHL, Cochrane
      Database of Systematic Reviews and EMBASE: Psychiatry. Searches were limited to
      English journals and books and to the last five years in the first instance, with
      earlier literature considered where appropriate. RESULTS: Maternal mental illness
      can impact negatively on a child's life, especially where an insecure attachment
      is formed between mother and baby during the important early developmental years.
      The potential sequelae of maternal mental illness for children include impaired
      cognitive development, behavioural difficulties and increased risk of psychiatric
      disorder. Effective parenting skills are suggested to be a protective factor
      against these sequelae. However, the effects of parenting programs for women with
      mental illness have not been empirically tested, so that the potential long-term
      benefits of such interventions are not known. CONCLUSIONS: Parenting skills
      training for women with mental illness may be a useful selective preventive
      intervention. It is unlikely generic programs will be suitable. Rather,
      interventions for women with a mental illness will need to address the commonly
      experienced parenting problems as well as the more specific needs of women with
      mental illness.

PMID- 15555027
TI  - Indices of social risk among first attenders of an emergency mental health
      service in post-conflict East Timor: an exploratory investigation.
AB  - OBJECTIVE: Little is known about the profile of patients treated in mental health
      services in low-income, post-conflict countries, especially in the post-emergency
      phase. We postulated that patients attending the first community mental health
      service in East Timor would be characterized not only by mental disturbance but
      by high levels of social vulnerability. METHOD: Drawing on existing methods and
      on consultations with East Timorese mental health staff, five social indicators
      were identified: dangerousness; inability to undertake life-sustaining self-care;
      bizarre behaviour; incapacitating distress; and social unmanageability. Adequate
      levels of interrater reliability (65-91%) were achieved in identifying these
      indicators from case notes. Forty-eight randomly selected case notes were
      analyzed to ascertain the prevalence of social risk factors as well as the
      referral source and broad diagnostic groupings. RESULTS: Major referral sources
      were the family, humanitarian agencies and the police. Twenty-nine percent met
      criteria for dangerousness; 42% for inability to undertake self-care; 58% for
      bizarre behaviour; 75% for distress; and 19% for unmanageability. Ninety-eight
      percent fulfilled at least one social indicator, with the modal score being 2.
      CONCLUSIONS: Although the approach to documentation and analysis was preliminary,
      the data suggest that a focus on social risk indicators may assist in determining
      those mentally disturbed persons in need of priority care in resource-poor post
      conflict countries.

PMID- 15555028
TI  - Do nations' mental health policies, programs and legislation influence their
      suicide rates? An ecological study of 100 countries.
AB  - OBJECTIVE: To test the hypothesis that the presence of national mental health
      policies, programs and legislation would be associated with lower national
      suicide rates. METHOD: Suicide rates from 100 countries were regressed on mental
      health policy, program and legislation indicators. RESULTS: Contrary to the
      hypothesized relationship, the study found that after introducing mental health
      initiatives (with the exception of substance abuse policies), countries' suicide
      rates rose. CONCLUSION: It is of concern that most mental health initiatives are
      associated with an increase in suicide rates. However, there may be acceptable
      reasons for the observed findings, for example initiatives may have been
      introduced in areas of increasing need, or a case-finding effect may be
      operating. Data limitations must also be considered.

PMID- 15555029
TI  - Association between lifestyle factors and mental health measures among community
      dwelling older women.
AB  - OBJECTIVE: To investigate the association between potentially modifiable
      lifestyle factors and cognitive abilities/depressive symptoms in community
      dwelling women aged 70 years and over. METHOD: Cross-sectional study of community
      dwelling women aged 70 years and over (n=278; mean age=74.6 years). Lifestyle
      variables assessed included smoking, alcohol consumption, physical activity,
      nutrition and education. The mental health measures of interest were depression,
      anxiety, quality of life and cognitive function, as assessed by the Beck
      Depression Inventory (BDI), Beck Anxiety Inventory (BAI), SF-36, and the
      Cambridge Cognitive Examination for Mental Disorders of the Elderly (CAMCOG),
      respectively. RESULTS: Physically active women were half as likely to be
      depressed (BDI score > or =10) and anxious (BAI score > or = 8) when compared to
      their physically inactive counterparts (OR=0.5, 95% CI=0.3-0.8 for both, adjusted
      for marital status and smoking in the case of depression). Having ever smoked
      more than 20 cigarettes per day was associated with increased risk of depression
      (OR=2.8, 95% CI=1.4-5.5, adjusted for marital status and physical activity).
      Moderate alcohol use was associated with increased likelihood of having a CAMCOG
      score within the highest 50 percentile (OR=2.0, 95% CI=1.1-3.5, adjusted for age
      and education), as was more than minimum statutory education (OR=2.0, 95% CI=1.1
      3.5, adjusted for age and alcohol consumption). There was no obvious association
      between vitamin B12/folate deficiency or obesity with any of the measures of
      interest. CONCLUSIONS: The results of this study are consistent with the
      hypothesis that depression is directly associated with heavy smoking and
      inversely associated with physical activity. They also support the idea that non
      harmful alcohol consumption is associated with better cognitive performance.
      Randomised clinical trials should be now designed to clarify whether management
      of lifestyle factors reduces the incidence of mood disorders and cognitive
      impairment in later life.

PMID- 15555030
TI  - Outcomes for elderly patients with mental illness following relocation from a
      stand-alone psychiatric hospital to community-based extended care units.
AB  - OBJECTIVE: To assess the outcomes for a group of elderly patients with mental
      illness following their discharge from a stand-alone psychiatric facility to
      seven extended care units (ECUs). METHOD: All patients (n=60) who were relocated
      to the ECUs were assessed using a number of standardized clinical and general
      functioning instruments at 6 months and 6 weeks pre-move, and again at 6 weeks, 6
      months and 18 months post-move. RESULTS: By 18 months post-discharge, 13 of the
      60 patients (21.7%) had died and seven others had been transferred to nursing
      homes. Those who died were older and had significantly higher levels of physical
      ill health when compared to those who did not die. Changes on measures of
      clinical and behavioural functioning in those who remained in the study did not
      reach statistical significance by 18 months post-move. However, participants did
      demonstrate improvements in quality of life with significantly higher scores on
      measures of social contact and community access. CONCLUSIONS: The mortality
      observed in the follow-up period is likely to be related to physical ill health
      and old age rather than the trauma associated with relocation. While overall
      functioning did not improve following relocation, patients had more independence
      and greater access to community-based activities.

PMID- 15555031
TI  - Dual relationships in mental health practice: issues for clinicians in rural
      settings.
AB  - OBJECTIVE: This paper aims to provide an overview of the literature on non-sexual
      dual relationships, and to discuss these in the context of rural mental health
      practice in Australia. METHOD: An internet-driven literature search was
      undertaken using OVID databases, which include MEDLINE, PsycINFO, CINAHL, and
      EMBASE: Psychiatry. Ethical codes of practice for the mental health professions
      of psychiatry, psychology, occupational therapy, social work and nursing were
      referred to. Searches were not limited by year of publication. Other unpublished
      material or information was included where relevant. RESULTS: Dual relationships
      are common in rural mental health practice. However, research on non-sexual dual
      relationship boundary issues in rural mental health is limited. Ethical codes of
      practice of mental health professional bodies provide little guidance regarding
      non-sexual dual relationships. Decision-making models addressing the ethics of
      dual relationships are restricted to considerations of whether to enter a dual
      relationship rather than how to manage such a relationship. CONCLUSIONS:
      Everyday' dual relationships are a predictable part of rural mental health
      practice. Further research is required to identify the benefits and/or problems
      in clinical practice resulting from non-sexual dual relationships. Responsibility
      for identifying and implementing ways of appropriately managing such
      relationships should be shared by the patient, the clinician, mental health
      services and professional organizations.

PMID- 15555032
TI  - Negative beliefs about self and illness: a comparison of individuals with
      psychosis with or without comorbid social anxiety disorder.
AB  - OBJECTIVE: This study set out to investigate whether socially anxious individuals
      with psychosis will perceive more loss, entrapment, shame and humiliation, will
      blame themselves more for their illness and have lower self-esteem than non
      socially anxious individuals with psychosis. METHOD: Two groups of participants
      with psychosis with (n=19) and without (n=19) social anxiety disorder were
      matched on the basis of gender and diagnosis. RESULTS: There were no differences
      between the two groups in terms of positive and negative symptoms. Participants
      with social anxiety had significantly higher levels of self-blame, entrapment,
      shame and lower self-esteem. Differences in entrapment, shame and self-esteem
      remained significant after controlling for depression. CONCLUSIONS: Negative
      beliefs about self and psychosis may be associated with the development of
      concurrent social anxiety disorder. The clinical and research implications of the
      findings are discussed.

PMID- 15555033
TI  - Disability and service use among homeless people living with psychotic disorders.
AB  - BACKGROUND: The prevalence of psychosis and needs for care among homeless people
      were studied in inner Melbourne. METHOD: This was a two-stage nested study within
      the Australian National Survey of People Living with Psychotic Illness. A screen
      for psychosis was administered to a representative sample of men and women living
      in marginal housing in a mental health service catchment area. A selected
      subsample of 82 screen-positive respondents was interviewed using the Diagnostic
      Interview for Psychosis (DIP), a semistructured, standardized interview with
      three modules: (i) demography, functioning and quality of life; (ii) diagnosis;
      and (iii) service use. RESULTS: An unexpectedly high prevalence of people living
      with psychotic disorders (estimated lifetime prevalence 42%, 95% CI=37-47%) may
      reflect a concentration of vulnerable people in the shrinking marginal housing
      supply in the inner city areas. Disability in everyday, occupational and social
      functioning is greater for this subgroup than for other people living with
      psychosis in Australia. Most people were single and unemployed, and many reported
      social isolation and feeling unsafe. Substance use disorders were common. Most
      people were using health services, including specialist mental health services,
      but few were receiving rehabilitation, vocational or housing support.
      CONCLUSIONS: Despite high levels of contact with a well-organized, sectorized
      mental health service in an affluent country, this pocket of several hundred
      people had high levels of persisting disability and needs. The literature and
      local experience suggest that changing this situation is likely to require co
      ordinated policy and practice between the health, welfare and housing sectors.

PMID- 15555034
TI  - Cycloid psychosis, catatonia, and periodic catatonia.

PMID- 15555035
TI  - Conditioned heroin 'overdose' death in a public toilet.

PMID- 15555036
TI  - Wernicke-Korsakoff syndrome and alcohol-induced persistent dementia.

PMID- 15555037
TI  - Guidelines for the treatment of depression.

PMID- 15555038
TI  - Randomized controlled trials of antidepressant medication.

PMID- 15555039
TI  - In protest.

PMID- 15555049
TI  - Rat models of skin wound healing: a review.
AB  - Rats have been widely used in the study of skin wound healing and the efficacy of
      different treatment modalities. This particular animal species is often selected
      for its availability, low cost, and small size. To define the current use of rat
      skin wound healing models, this manuscript provides a review of articles
      published between 2000 and 2003 that chose rats as their research animals. Of the
      55 articles reviewed, it was found that 38.2% of the studies used incisional
      models and 38.2% used excisional models, with some studies using combinations.
      The majority of the studies (78.2%) used the rat's dorsum as the wound location.
      Male Sprague Dawley in the 250-300 gram weight range were the most preferred
      rats. Sodium pentobarbital/pentobarbitone was the most commonly used anesthetic
      choice. Similarities and differences in the selected experimental conditions are
      noted and questions are raised with regard to comparability between studies and
      the ability to transfer the data from the animal model to the human clinical
      situation. Attempts to compare studies for the advancement of wound healing
      knowledge are being hampered by the differences found between the studies.
      Standardization in reporting could facilitate comparisons and may instigate
      additional research that favors the inevitable comparisons between the studies.
      Thus, universal reporting requirements need to be developed for animal wound
      healing studies.

PMID- 15555050
TI  - Effects of vacuum-assisted closure therapy on inguinal wound edge microvascular
      blood flow.
AB  - Vacuum-assisted closure (VAC) therapy has been shown to facilitate wound healing.
      Data on the mechanisms are scarce, although beneficial effects on blood flow and
      granulation tissue formation have been presented. In the current study, laser
      Doppler was used to measure microvascular blood flow to an inguinal wound in pigs
      during VAC therapy (-50 to -200 mmHg), including consideration of the different
      tissue types and the distance from the wound edge. VAC treatment induced an
      increase in microvascular blood flow a few centimeters from the wound edge. The
      increase in blood flow occurred closer to the wound edge in muscular as compared
      to subcutaneous tissue (1.5 cm and 3 cm, at -75 mmHg). In the immediate proximity
      to the wound edge, blood flow was decreased. This hypoperfused zone was increased
      with decreasing pressure and was especially prominent in subcutaneous as compared
      to muscular tissue (0-1.9 cm vs. 0-1.0 cm, at -100 mmHg). When VAC therapy was
      terminated, blood flow increased multifold, which may be due to reactive
      hyperemia. In conclusion, VAC therapy affects microvascular blood flow to the
      wound edge and may thereby promote wound healing. A low negative pressure during
      treatment may be beneficial, especially in soft tissue, to minimize possible
      ischemic effects. Intermittent VAC therapy may further increase blood flow.

PMID- 15555051
TI  - Protective effects of a free radical scavenger, MCI-186, on high-glucose-induced
      dysfunction of human dermal microvascular endothelial cells.
AB  - Functional damage to microvascular endothelial cells by hyperglycemia is thought
      to be one of the critical risk factors in the impaired wound healing seen with
      diabetes mellitus. It is also thought that free radical stress plays a
      significant role in this endothelial cell dysfunction. In the present study, the
      effect of a free radical scavenger, MCI 186, on the endothelial cell dysfunction
      of cultured cells induced by high-glucose conditions was studied. Human dermal
      microvascular endothelial cells were cultured with high-glucose medium (50 mM)
      with or without MCI-186 (10 microM) for 7 days. Fifty mM mannitol was used as an
      osmotic control in this study. After this treatment, cell proliferation,
      activation of mitogen-activated protein kinase (MAPK), the level of apoptosis,
      and caspase-3 activation induced by removal of growth factors or tumor necrosis
      factor-alpha treatment were studied. High-glucose conditions significantly
      decreased cell proliferation and increased apoptosis levels with the activation
      of caspase-3 induced by growth factor removal. The high-glucose condition
      significantly activated MAPK. MCI-186 treatment improved cellular proliferation
      and reduced apoptosis and caspase-3 activation induced by high-glucose
      conditions. MCI-186 also inhibited the activation of MAPK. On the other hand, MCI
      186 did not alter the level of apoptosis and caspase-3 activation induced by TNF
      alpha treatment. In conclusion, we suggest that MCI-186 may be beneficial for
      improving the endothelial cell dysfunction induced by hyperglycemia.

PMID- 15555052
TI  - Culture confluence regulates gene expression of normal human keratinocytes.
AB  - Keratinocytes are frequently used to examine efficacy of wound healing products
      and dermatological agents in vitro. Cultured keratinocyte sheets are also used as
      autologous or allogenic grafts to promote wound closure. Because it is well known
      that the expression patterns of keratin genes change when cell cultures reach
      confluence, we investigated the expression pattern of wound healing-related
      genes, including growth factors and cytokines. Of additional particular interest
      is a novel wound healing related factor, secretory leukocyte protease inhibitor
      (SLPI), which appears to enhance tissue repair. We found that the expression
      pattern varied for specific genes expressed by keratinocytes as confluence was
      reached. Specifically, SLPI expression peaked in the early postconfluent state
      and vascular endothelial growth factor and amphiregulin in the late postconfluent
      state. Some gene products exhibit autocrine activity, whereas others exert
      paracrine regulation of growth. These findings indicate that it is critical to
      define the growth and differentiation state of human keratinocyte cultures to
      better determine responses and efficacy in vitro to various dermatological/wound
      care agents tested.

PMID- 15555053
TI  - Celosia argentea Linn. leaf extract improves wound healing in a rat burn wound
      model.
AB  - Celosia argentea (CA) is used in traditional medicine for sores, ulcers, and skin
      eruptions. The present study was aimed at investigating the healing efficacy of
      CA extract in an ointment formulated (10 % w/w) as an alcohol extract of CA using
      a rat burn wound model. Wound closure occurred earlier in the treated rats (15
      days vs. 30 in the untreated group; p < 0.05). Granulation tissue collected on
      every fifth day of healing showed an increase in collagen and hexosamine content
      at a faster rate in the treated wounds. This correlated with the accelerated
      wound closure observed in the treated groups. To probe the cellular basis of this
      effect, we investigated the effect of this extract on two major cellular
      responses; cell proliferation and cell motility, in two key cell lineages,
      fibroblasts and keratinocytes. CA was not toxic at concentrations of < 3
      microg/ml in fibroblasts and < 30 microg/ml in keratinocytes. The alcohol extract
      promoted cell motility and proliferation of primary dermal fibroblasts at 0.1-1.0
      microg/ml but did not alter these responses in primary keratinocytes. In an
      initial examination of molecular mechanisms, we found that the CA extract did not
      alter fibroblast and keratinocyte responses to the wound repair-associated
      epidermal growth factor receptor ligands. In short, we demonstrate a salutary
      action of the CA extract on wound healing, and suggest that this may be due to
      mitogenic and motogenic promotion of dermal fibroblasts.

PMID- 15555054
TI  - Developments in xenobiotic-free culture of human keratinocytes for clinical use.
AB  - We have recently reported that irradiated human fibroblasts can be used as a
      feeder layer, to expand keratinocytes under serum-free conditions, on a
      chemically defined plasma polymer surface developed for the culture and transfer
      of keratinocytes for clinical use. While this is a significant advance in
      developing a serum-free keratinocyte culture approach, the need to irradiate
      fibroblasts to growth-arrest them and prevent them from overgrowing the
      keratinocytes introduces another small, but potential, risk for the patient. The
      aim of the present study was to develop conditions for the coculture of normal
      human keratinocytes with nonirradiated normal human fibroblasts under serum-free
      conditions. We examined the fibroblast/keratinocyte relationship on three
      separate surfaces: tissue culture plastic, non-tissue culture plastic, and a
      plasma polymer surface designed for clinical use. We report that it is possible
      to achieve rapid and successful expansion of human keratinocytes under serum-free
      conditions on all three surfaces providing one uses a keratinocyte-friendly
      media, a minimum seeding density of keratinocytes, and a ratio of fibroblasts to
      keratinocytes that does not exceed 1:1. These results provide us with a rapid
      laboratory expansion of proliferative human keratinocytes, under completely
      defined culture conditions, without any xenobiotic cells (mouse fibroblasts) or
      material (bovine serum), for the treatment of patients with extensive skin loss.

PMID- 15555055
TI  - Approaches to improve angiogenesis in tissue-engineered skin.
AB  - A problem with tissue-engineered skin is clinical failure due to delays in
      vascularization. The aim of this study was to explore a number of simple
      strategies to improve angiogenesis/vascularization using a tissue-engineered
      model of skin to which small vessel human dermal microvascular endothelial cells
      were added. For the majority of these studies, a modified Guirguis chamber was
      used, which allowed the investigation of several variables within the same
      experiment using the same human dermis; cell type, angiogenic growth factors, the
      influence of keratinocytes and fibroblasts, mechanical penetration of the human
      dermis, the site of endothelial cell addition, and the influence of hypoxia were
      all examined. A qualitative scoring system was used to assess the impact of these
      factors on the penetration of endothelial cells throughout the dermis. Similar
      results were achieved using freshly isolated small vessel human dermal
      microvascular endothelial cells or an endothelial cell line and a minimum cell
      seeding density was identified. Cell penetration was not influenced by the
      addition of angiogenic growth factors (vascular endothelial growth factor and
      basic fibroblast growth factor); similarly, including epidermal keratinocytes or
      dermal fibroblasts did not encourage endothelial cell entry, and neither did
      mechanical introduction of holes throughout the dermis. Two factors were
      identified that significantly enhanced endothelial cell penetration into the
      dermis: hypoxia and the site of endothelial cell addition. Endothelial cells
      added from the papillary surface entered into the dermis much more effectively
      than when cells were added to the reticular surface of the dermis. We conclude
      that this model is valuable in improving our understanding of how to enhance
      vascularization of tissue-engineered grafts.

PMID- 15555056
TI  - Experimental induction of heterotopic bone in abdominal implants.
AB  - Induction of bone tissue requires three elements: osteoprogenitor cells,
      osteoinductive factors, and a supporting extracellular matrix. In this study, we
      report on an experimental model in dogs of heterotopic bone tissue production,
      based on the integration of these osteo-inductive factors into abdominal
      implants. The implants consist of either a type I collagen sponge wrapped with
      periosteum and omentum or a type I collagen sponge embedded with demineralized
      bone powder, platelet-rich plasma, thrombin, and calcium chloride wrapped with
      omentum, with or without periosteum. Automated histomorphometric analysis showed
      an efficient production of trabecular bone, which corresponded to 50-70% of the
      total tissue composition 4 months after implant formation. High expression of the
      osteoinductive cytokines transforming growth factor-beta and bone morphogenetic
      proteins-2 and -4 was shown by immunohistochemistry in macrophages, endothelial
      cells from neoformed capillaries, osteoblasts, osteoclasts, and the mesenchymal
      tissue around the bone trabeculae. These approaches are novel and efficient
      surgical procedures to produce mature trabecular bone that could be used as a
      potential source of bone tissue for autotransplantation.

PMID- 15555057
TI  - Direct effects of interleukin-6 on liver progenitor oval cells in culture.
AB  - Following acute injury, liver is usually regenerated from hepatocytes by a
      process that is dependent on interleukin (IL)-6. If this pathway is impaired,
      restoration of the liver mass and ultimately the survival of the animal are
      dependent on recruitment of cells from a precursor cell population, either a stem
      cell or an oval cell. Importantly, oval cells are also implicated in
      tumorigenesis. A carcinogenic choline-deficient ethionine supplemented (CDE) diet
      is capable of inducing substantial numbers of oval cells that we can isolate and
      utilize to identify cytokines, which affect oval cell proliferation and
      differentiation. Currently, a putative role of IL-6 in oval cell biology is
      suggested by the elevation of IL-6 in liver and serum of mice treated with a CDE
      diet and knockout mouse studies. Also, when IL-6 is injected into the peritoneal
      cavity of mice on the CDE diet, oval cell numbers are increased compared to mice
      on the CDE diet alone. We investigated the role of human IL-6 on p53 null
      immortalized murine oval cell lines (PIL), finding that they express transcripts
      for the IL-6 receptor and gp 130, STAT-3 is phosphorylated upon IL-6 stimulation,
      IL-6 induces IL-6 production, and proliferation is induced by IL-6. In addition,
      we show that mouse primary oval cells also express IL-6 receptor and gp 130 mRNA.
      These findings suggest that IL-6 directly stimulates oval cells and an autocrine
      mechanism may sustain oval cell proliferation.

PMID- 15555058
TI  - Number, frequency, self-renewal, and expansion of osteoprogenitor cells (CFU-O)
      in subcultured female rat vertebral cell populations.
AB  - The present study was undertaken to determine whether the frequency and/or number
      of dexamethasone- and progesterone-responsive osteoprogenitors in cell
      populations derived from vertebrae of 6-week-old female rats could be increased
      relative to that of other progenitors. Frequencies and numbers of both progenitor
      types were determined for up to six subcultures using continuous subculturing,
      limiting dilution analysis, and colony assays. In dexamethasone-containing
      medium, subculturing resulted in an eightfold increase in the total number of
      dexamethasone-responsive osteoprogenitors and a 14-fold increase in progesterone
      responsive osteoprogenitors in second subculture cells over first subculture
      cells without a significant increase in the frequency of these progenitors. From
      the third subculture onward, the frequency of both classes of osteoprogenitors
      decreased in a linear manner and none were observed after six subcultures.
      Similar results were obtained in progesterone-containing medium. Limiting
      dilution analysis in the presence of dexamethasone indicated that 2.61 % of cells
      represented a colony forming unit-fibroblast and 0.28 % represented an
      osteoprogenitor in first subculture cells, while in second subculture cells,
      these frequencies increased to 5.56 % and 0.40 %, respectively. Results show that
      while the frequency of colony forming unit-osteoprogenitor is not increased in
      the second subculture over the first, the total number of osteoprogenitors is
      greatly increased because of expansion of the total progenitor cell pool.

PMID- 15555059
TI  - Prevalence and determinants of diabetes mellitus among Iranian patients with
      chronic liver disease.
AB  - BACKGROUND: Alterations in carbohydrate metabolism are frequently observed in
      cirrhosis. We conducted this study to define the prevalence of diabetes mellitus
      (DM) and impaired glucose tolerance (IGT) in Iranian patients with chronic liver
      disease (CLD), and explore the factors associated with DM in these patients.
      METHODS: One hundred and eighty-five patients with CLD were enrolled into the
      study. Fasting plasma glucose and two-hour plasma glucose were measured in
      patients' sera. DM and IGT were diagnosed according to the latest American
      Diabetes Association criteria. RESULTS: The subjects included 42 inactive HBV
      carriers with a mean age of 42.2 +/- 12.0 years, 102 patients with HBV or HCV
      chronic hepatitis with a mean age of 41.2 +/- 10.9 years, and 41 cirrhotic
      patients with a mean age of 52.1 +/- 11.4 years. DM and IGT were diagnosed in 40
      (21.6%) and 21 (11.4%) patients, respectively. Univariate analysis showed that
      age (P = 0.000), CLD status (P = 0.000), history of hypertension (P = 0.007),
      family history of DM (P = 0.000), and body mass index (BMI) (P = 0.009) were
      associated with DM. Using Multivariate analysis, age (OR = 4.7, 95%CI: 1.8-12.2),
      family history of DM (OR = 6.6, 95%CI: 2.6-17.6), chronic hepatitis (OR = 11.6,
      95%CI: 2.9-45.4), and cirrhosis (OR = 6.5, 95%CI: 2.4-17.4) remained as the
      factors independently associated with DM. When patients with cirrhosis and
      chronic hepatitis were analyzed separately, higher Child-Pugh's score in
      cirrhotic patients (OR = 9.6, 95%CI: 1.0-88.4) and older age (OR = 7.2, 95%CI:
      1.0-49.1), higher fibrosis score (OR = 59.5, 95%CI: 2.9-1211.3/ OR = 11.9, 95%CI:
      1.0-132.2), and higher BMI (OR = 30.3, 95%CI: 3.0-306.7) in patients with chronic
      hepatitis were found to be associated with higher prevalence of DM. CONCLUSIONS:
      Our findings indicate that patients with cirrhosis and chronic hepatitis are at
      the increased risk of DM occurrence. Older age, severe liver disease, and obesity
      were associated with DM in these patients.

PMID- 15555060
TI  - Performance of a genetic algorithm for mass spectrometry proteomics.
AB  - BACKGROUND: Recently, mass spectrometry data have been mined using a genetic
      algorithm to produce discriminatory models that distinguish healthy individuals
      from those with cancer. This algorithm is the basis for claims of 100%
      sensitivity and specificity in two related publicly available datasets. To date,
      no detailed attempts have been made to explore the properties of this genetic
      algorithm within proteomic applications. Here the algorithm's performance on
      these datasets is evaluated relative to other methods. RESULTS: In reproducing
      the method, some modifications of the algorithm as it is described are necessary
      to get good performance. After modification, a cross-validation approach to model
      selection is used. The overall classification accuracy is comparable though not
      superior to other approaches considered. Also, some aspects of the process rely
      upon random sampling and thus for a fixed dataset the algorithm can produce many
      different models. This raises questions about how to choose among competing
      models. How this choice is made is important for interpreting sensitivity and
      specificity results as merely choosing the model with lowest test set error rate
      leads to overestimates of model performance. CONCLUSIONS: The algorithm needs to
      be modified to reduce variability and care must be taken in how to choose among
      competing models. Results derived from this algorithm must be accompanied by a
      full description of model selection procedures to give confidence that the
      reported accuracy is not overstated.

PMID- 15555061
TI  - Weather-based prediction of Plasmodium falciparum malaria in epidemic-prone
      regions of Ethiopia II. Weather-based prediction systems perform comparably to
      early detection systems in identifying times for interventions.
AB  - BACKGROUND: Timely and accurate information about the onset of malaria epidemics
      is essential for effective control activities in epidemic-prone regions. Early
      warning methods that provide earlier alerts (usually by the use of weather
      variables) may permit control measures to interrupt transmission earlier in the
      epidemic, perhaps at the expense of some level of accuracy. METHODS: Expected
      case numbers were modeled using a Poisson regression with lagged weather factors
      in a 4th-degree polynomial distributed lag model. For each week, the numbers of
      malaria cases were predicted using coefficients obtained using all years except
      that for which the prediction was being made. The effectiveness of alerts
      generated by the prediction system was compared against that of alerts based on
      observed cases. The usefulness of the prediction system was evaluated in cold and
      hot districts. RESULTS: The system predicts the overall pattern of cases well,
      yet underestimates the height of the largest peaks. Relative to alerts triggered
      by observed cases, the alerts triggered by the predicted number of cases
      performed slightly worse, within 5% of the detection system. The prediction-based
      alerts were able to prevent 10-25% more cases at a given sensitivity in cold
      districts than in hot ones. CONCLUSIONS: The prediction of malaria cases using
      lagged weather performed well in identifying periods of increased malaria cases.
      Weather-derived predictions identified epidemics with reasonable accuracy and
      better timeliness than early detection systems; therefore, the prediction of
      malarial epidemics using weather is a plausible alternative to early detection
      systems.

PMID- 15555062
TI  - Good vs complementary genes for parasite resistance and the evolution of mate
      choice.
AB  - BACKGROUND: Female mate choice may be adaptive when males exhibit heritable
      genetic variation at loci encoding resistance to infectious disease. The Hamilton
      Zuk hypothesis predicts that females should assess the genetic quality of males
      by monitoring traits that indicate health and vigor (condition-dependent choice,
      or CD). Alternatively, some females may employ a more direct method of screening
      and select mates based on the dissimilarity of alleles at the major
      histocompatibility loci (we refer to this as opposites-attract, or OA). Empirical
      studies suggest that both forms of mate choice exist, but little is known about
      the potential for natural selection to shape the two strategies in nature.
      RESULTS: We used computer simulation models to examine the evolutionary fates of
      the two forms of mate choice in populations at risk for infection by debilitating
      parasites. We found that populations exhibiting random mating (no mate choice)
      can be invaded and replaced completely by individuals practicing CD type mate
      choice. We also found that an allele encoding OA choice can increase when rare in
      randomly mating populations, but that it does not go to fixation under selection.
      A similar result was obtained when the OA strategy was introduced into
      populations practicing CD mate choice. As before, we found that the OA choice
      allele will increase when rare, and that it will not go to fixation under
      selection. The converse however was not true, as CD individuals gain no rare
      advantage when introduced into an OA population. CONCLUSIONS: Taken together, the
      results suggest that, when rare, OA is the best strategy for parasite evasion (of
      those considered here). The consequence of OA increasing in the population,
      however, is to reduce the parasite driven genotype oscillations and facilitate
      the breakdown of linkage disequilibrium at the disease-resistance loci. This
      leads to a neutrally stable situation in which different strategies have equal
      fitness, and suggests that multiple forms of mate choice may be expected to occur
      in populations at risk from infectious disease.

PMID- 15555063
TI  - Widespread presence of "bacterial-like" PPP phosphatases in eukaryotes.
AB  - BACKGROUND: In eukaryotes, PPP (protein phosphatase P) family is one of the two
      known protein phosphatase families specific for Ser and Thr. The role of PPP
      phosphatases in multiple signaling pathways in eukaryotic cell has been
      extensively studied. Unlike eukaryotic PPP phosphatases, bacterial members of the
      family have broad substrate specificity or may even be Tyr-specific. Moreover,
      one group of bacterial PPPs are diadenosine tetraphosphatases, indicating that
      bacterial PPP phosphatases may not necessarily function as protein phosphatases.
      RESULTS: We describe the presence in eukaryotes of three groups of expressed
      genes encoding "non-conventional" phosphatases of the PPP family. These enzymes
      are more closely related to bacterial PPP phosphatases than to the known
      eukaryotic members of the family. One group, found exclusively in land plants, is
      most closely related to PPP phosphatases from some alpha-Proteobacteria,
      including Rhizobiales, Rhodobacterales and Rhodospirillaceae. This group is
      therefore termed Rhizobiales / Rhodobacterales / Rhodospirillaceae-like
      phosphatases, or Rhilphs. Phosphatases of the other group are found in
      Viridiplantae, Rhodophyta, Trypanosomatidae, Plasmodium and some fungi. They are
      structurally related to phosphatases from psychrophilic bacteria Shewanella and
      Colwellia, and are termed Shewanella-like phosphatases, or Shelphs. Phosphatases
      of the third group are distantly related to ApaH, bacterial diadenosine
      tetraphosphatases, and are termed ApaH-like phosphatases, or Alphs. Patchy
      distribution of Alphs in animals, plants, fungi, diatoms and kinetoplasts
      suggests that these phosphatases were present in the common ancestor of
      eukaryotes but were independently lost in many lineages. Rhilphs, Shelphs and
      Alphs form PPP clades, as divergent from "conventional" eukaryotic PPP
      phosphatases as they are from each other and from major bacterial clades. In
      addition, comparison of primary structures revealed a previously unrecognised
      (I/L/V)D(S/T)G motif, conserved in all bacterial and "bacterial-like" eukaryotic
      PPPs, but not in "conventional" eukaryotic and archaeal PPPs. CONCLUSIONS: Our
      findings demonstrate that many eukaryotes possess diverse "bacterial-like" PPP
      phosphatases, the enzymatic characteristics, physiological roles and precise
      evolutionary history of which have yet to be determined.

PMID- 15555064
TI  - Health-related quality of life among adolescents with allergy-like conditions -
      with emphasis on food hypersensitivity.
AB  - BACKGROUND: It is known that there is an increase in the prevalence of allergy
      and that allergic diseases have a negative impact on individuals' health-related
      quality of life (HRQL). However, research in this field is mainly focused on
      individuals with verified allergy, i.e. leaving out those with self-reported
      allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on
      food hypersensitivity and quality of life are scarce. In order to receive
      information about the extent to which adolescent females and males experience
      allergy-like conditions and the impact of these conditions on their everyday
      life, the present study aimed to investigate the magnitude of self-reported
      allergy-like conditions in adolescence and to evaluate their HRQL. Special focus
      was put on food hypersensitivity as a specific allergy-like condition and on
      gender differences. METHODS: In connection with lessons completed at the
      children's school, a study-specific questionnaire and the generic instrument SF
      36 were distributed to 1488 adolescents, 13-21 years old (response rate 97%).
      RESULTS: Sixty-four per cent of the respondents reported some kind of allergy
      like condition: 46% reported hypersensitivity to defined substances and 51%
      reported allergic diseases (i.e. asthma/wheezing, eczema/rash, rhino
      conjunctivitis). A total of 19% reported food hypersensitivity. Females more
      often reported allergy-like conditions compared with males (p < 0.001). The
      adolescents with allergy-like conditions reported significantly lower HRQL (p <
      0.001) in seven of the eight SF-36 health scales compared with adolescents
      without such conditions, regardless of whether the condition had been doctor
      diagnosed or not. Most adolescents suffered from complex allergy-like conditions.
      CONCLUSIONS: The results indicate a need to consider the psychosocial impact of
      allergy-like conditions during school age. Further research is needed to
      elucidate the gender differences in this area. A team approach addressing better
      understanding of how allergy-like conditions impair the HRQL may improve the
      management of the adolescent's health problems, both in health-care services and
      in schools.

PMID- 15555065
TI  - Assessment of FIV-C infection of cats as a function of treatment with the
      protease inhibitor, TL-3.
AB  - BACKGROUND: The protease inhibitor, TL-3, demonstrated broad efficacy in vitro
      against FIV, HIV and SIV (simian immunodeficiency virus), and exhibited very
      strong protective effects on early neurologic alterations in the CNS of FIV-PPR
      infected cats. In this study, we analyzed TL-3 efficacy using a highly pathogenic
      FIV-C isolate, which causes a severe acute phase immunodeficiency syndrome, with
      high early mortality rates. RESULTS: Twenty cats were infected with uncloned FIV
      C and half were treated with TL-3 while the other half were left untreated. Two
      uninfected cats were used as controls. The general health and the immunological
      and virological status of the animals was monitored for eight weeks following
      infection. All infected animals became viremic independent of TL-3 treatment and
      seven of 20 FIV-C infected animals developed severe immunodepletive disease in
      conjunction with significantly (p < or = 0.05) higher viral RNA loads as compared
      to asymptomatic animals. A marked and progressive increase in CD8+ T lymphocytes
      in animals surviving acute phase infection was noted, which was not evident in
      symptomatic animals (p < or = 0.05). Average viral loads were lower in TL-3
      treated animals and of the 6 animals requiring euthanasia, four were from the
      untreated cohort. At eight weeks post infection, half of the TL-3 treated animals
      and only one of six untreated animals had viral loads below detection limits.
      Analysis of protease genes in TL-3 treated animals with higher than average viral
      loads revealed sequence variations relative to wild type protease. In particular,
      one mutant, D105G, imparted 5-fold resistance against TL-3 relative to wild type
      protease. CONCLUSIONS: The findings indicate that the protease inhibitor, TL-3,
      when administered orally as a monotherapy, did not prevent viremia in cats
      infected with high dose FIV-C. However, the modest lowering of viral loads with
      TL-3 treatment, the greater survival rate in symptomatic animals of the treated
      cohort, and the lower average viral load in TL-3 treated animals at eight weeks
      post infection is indicative of a therapeutic effect of the compound on virus
      infection.

PMID- 15555066
TI  - Evaluation of an inter-professional workshop to develop a psychosocial assessment
      and child-centred communication training programme for paediatricians in
      training.
AB  - BACKGROUND: The quality of psychosocial assessment of children in consultations
      varies widely. One reason for this difference is the variability in effective
      mental health and communication training at undergraduate and post-qualification
      levels. In recognition of this problem, the Royal College of Paediatrics and
      Child Health in the United Kingdom have developed the Child in Mind Project that
      aims to meet this deficit in medical training. This paper describes the
      evaluation of a workshop that explored the experiences and expectations of health
      care professionals in the development of a training programme for doctors.
      METHODS: The one-day inter-professional workshop was attended by 63 participants
      who were invited to complete evaluation forms before and immediately after the
      workshop. RESULTS: The results showed that the workshop was partially successful
      in providing an opportunity for an inter-professional group to exchange ideas and
      influence the development of a significant project. Exploring the content and
      process of the proposed training programme and the opportunity for participants
      to share experiences of effective practice were valued. Participants identified
      that the current culture within many health care settings would be an obstacle to
      successful implementation of a training programme. Working within existing
      training structures will be essential. Areas for improvement in the workshop
      included clearer statement of goals at the outset and a more suitable environment
      for the numbers of participants. CONCLUSIONS: The participants made a valuable
      contribution to the development of the training programme identifying specific
      challenges. Inter-professional collaborations are likely to result in more
      deliverable and relevant training programmes. Continued consultation with
      potential users of the programme - both trainers and trainees will be essential.

PMID- 15555067
TI  - alpha1-antitrypsin and its C-terminal fragment attenuate effects of degranulated
      neutrophil-conditioned medium on lung cancer HCC cells, in vitro.
AB  - BACKGROUND: Tumor microenvironment, which is largely affected by inflammatory
      cells, is a crucial participant in the neoplastic process through promotion of
      cell proliferation, survival and migration. We measured the effects of
      polymorphonuclear neutrophil (PMN) conditioned medium alone, and supplemented
      with serine proteinase inhibitor alpha-1 antitrypsin (AAT) or its C-terminal
      fragment (C-36 peptide), on cultured lung cancer cells. METHODS: Lung cancer HCC
      cells were grown in a regular medium or in a PMN-conditioned medium in the
      presence or absence of AAT (0.5 mg/ml) or its C-36 peptide (0.06 mg/ml) for 24 h.
      Cell proliferation, invasiveness and release of IL-8 and VEGF were analyzed by
      [3H]-thymidine incorporation, Matrigel invasion and ELISA methods, respectively.
      RESULTS: Cells exposed to PMN-conditioned medium show decreased proliferation and
      IL-8 release by 3.9-fold, p < 0.001 and 1.3-fold, p < 0.05, respectively, and
      increased invasiveness by 2-fold (p < 0.001) compared to non-treated controls. In
      the presence of AAT, PMN-conditioned medium loses its effects on cell
      proliferation, invasiveness and IL-8 release, whereas VEGF is up-regulated by 3.7
      fold (p < 0.001) compared to controls. Similarly, C-36 peptide abolishes the
      effects of PMN-conditioned medium on cell invasiveness, but does not alter its
      effects on cell proliferation, IL-8 and VEGF release. Direct HCC cell exposure to
      AAT enhances VEGF, but inhibits IL-8 release by 1.7-fold (p < 0.001) and 1.4-fold
      (p < 0.01) respectively, and reduces proliferation 2.5-fold (p < 0.01). In
      contrast, C-36 peptide alone did not affect these parameters, but inhibited cell
      invasiveness by 51.4% (p < 0.001), when compared with non-treated controls.
      CONCLUSIONS: Our data provide evidence that neutrophil derived factors decrease
      lung cancer HCC cell proliferation and IL-8 release, but increase cell
      invasiveness. These effects were found to be modulated by exogenously present
      serine proteinase inhibitor, AAT, and its C-terminal fragment, which points to a
      complexity of the relationships between tumor cell biological activities and
      local microenvironment.

PMID- 15555068
TI  - Supracubital perineurioma misdiagnosed as carpal tunnel syndrome: case report.
AB  - BACKGROUND: Perineuriomas have been defined as tumorous lesions of the peripheral
      nerves which derive from perineurial cell proliferation and may be associated
      with abnormalities on chromosome 22. CASE PRESENTATION: Three years after a
      painful cubital vein procaine injection, a 33 year-old man developed a median
      nerve lesion, initially diagnosed as carpal tunnel syndrome. Symptoms progressed
      despite appropriate surgery. Clinical and electrophysiological re-evaluation
      revealed a fusiform mass at the distal upper arm, confirmed by MRI.
      Immunohistochemical studies classified the tumor as a mixed perineurioma and
      neuroma. CONCLUSIONS: Perineurioma mixed with neuroma may potentially caused by
      the previous trauma or cytotoxic effects of procaine.

PMID- 15555069
TI  - Spectrum of clinical disease in a series of 135 hospitalised HIV-infected
      patients from north India.
AB  - BACKGROUND: Literature on the spectrum of opportunistic disease in human
      immunodeficiency virus (HIV)-infected patients from developing countries is
      sparse. The objective of this study was to document the spectrum and determine
      the frequency of various opportunistic infections (OIs) and non-infectious
      opportunistic diseases, in hospitalised HIV-infected patients from north India.
      METHODS: One hundred and thirty five consecutive, HIV-infected patients (age 34
      +/- 10 years, females 17%) admitted to a tertiary care hospital in north India,
      for the evaluation and management of an OI or HIV-related disorder between
      January 2000 and July 2003, were studied. RESULTS: Fever (71%) and weight loss
      (65%) were the commonest presenting symptoms. Heterosexual transmission was the
      commonest mode of HIV-acquisition. Tuberculosis (TB) was the commonest OI (71%)
      followed by candidiasis (39.3%), Pneumocystis jiroveci pneumonia (PCP) (7.4%),
      cryptococcal meningitis and cerebral toxoplasmosis (3.7% each). Most of the cases
      of TB were disseminated (64%). Apart from other well-recognised OIs, two patients
      had visceral leishmaniasis. Two cases of HIV-associated lymphoma were
      encountered. CD4+ cell counts were done in 109 patients. Majority of the patients
      (82.6%) had CD4+ counts <200 cells/microL. Fifty patients (46%) had CD4+ counts
      <50 cells/microL. Only 50 patients (37%) received antiretroviral therapy. Twenty
      one patients (16%) died during hospital stay. All but one deaths were due to TB
      (16 patients; 76%) and PCP (4 patients; 19%). CONCLUSIONS: A wide spectrum of
      disease, including both OIs and non-infectious opportunistic diseases, is seen in
      hospitalised HIV-infected patients from north India. Tuberculosis remains the
      most common OI and is the commonest cause of death in these patients.

PMID- 15555070
TI  - Diversity and specificity in the interaction between Caenorhabditis elegans and
      the pathogen Serratia marcescens.
AB  - BACKGROUND: Co-evolutionary arms races between parasites and hosts are considered
      to be of immense importance in the evolution of living organisms, potentially
      leading to highly dynamic life-history changes. The outcome of such arms races is
      in many cases thought to be determined by frequency dependent selection, which
      relies on genetic variation in host susceptibility and parasite virulence, and
      also genotype-specific interactions between host and parasite. Empirical evidence
      for these two prerequisites is scarce, however, especially for invertebrate
      hosts. We addressed this topic by analysing the interaction between natural
      isolates of the soil nematode Caenorhabditis elegans and the pathogenic soil
      bacterium Serratia marcescens. RESULTS: Our analysis reveals the presence of i)
      significant variation in host susceptibility, ii) significant variation in
      pathogen virulence, and iii) significant strain- and genotype-specific
      interactions between the two species. CONCLUSIONS: The results obtained support
      the previous notion that highly specific interactions between parasites and
      animal hosts are generally widespread. At least for C. elegans, the high
      specificity is observed among isolates from the same population, such that it may
      provide a basis for and/or represent the outcome of co-evolutionary adaptations
      under natural conditions. Since both C. elegans and S. marcescens permit
      comprehensive molecular analyses, these two species provide a promising model
      system for inference of the molecular basis of such highly specific interactions,
      which are as yet unexplored in invertebrate hosts.

PMID- 15555071
TI  - Biotechnology approach to determination of genetic and epigenetic control in
      cells.
AB  - A series of studies aimed at developing methods and systems for analyzing
      epigenetic information in cells are presented. The role of the epigenetic
      information of cells, which is complementary to their genetic information, was
      inferred by comparing the predictions of genetic information with the cell
      behaviour observed under conditions chosen to reveal adaptation processes and
      community effects. Analysis of epigenetic information was developed starting from
      the twin complementary viewpoints of cells regulation as an 'algebraic' system
      (emphasis on the temporal aspect) and as a 'geometric' system (emphasis on the
      spatial aspect). The knowlege acquired from this study will lead to the use of
      cells for fully controlled practical applications like cell-based drug screening
      and the regeneration of organs.

PMID- 15555072
TI  - Socio-demographic factors and edentulism: the Nigerian experience.
AB  - BACKGROUND: The rate of total edentulism is said to be increasing in developing
      countries and this had been attributed mainly to the high prevalence of
      periodontal diseases and caries. Several reports have shown that non-disease
      factors such as attitude, behavior, dental attendance, characteristics of health
      care systems and socio-demographic factors play important roles in the
      aetiopathogenesis of edentulism. The aim of this study was to assess the
      relationship between socio-demographic factors and edentulism. METHODS: A total
      of 152 patients made up of 80 (52.6%) males and 72 (47.4%) females who presented
      in two prosthetic clinics located in an urban and a rural area were included in
      the study. The relationship between gender, age, socio-economic status and
      edentulism in this study population was established. RESULTS: No significant
      relationship between gender and denture demand was noted in the study. The demand
      for complete dentures increased with age while the demand for removable partial
      dentures also increased with age until the 3rd decade and then started to
      decline. A significant relationship was found between denture demand and the
      level of education with a higher demand in lower educational groups (p < 0.001).
      In addition, the lower socio-economic group had a higher demand more for
      prostheses than the higher group. CONCLUSIONS: The findings in this study
      revealed a significant relationship between socio-demographic variables and
      edentulism with age, educational level and socio-economic status playing vital
      roles in edentulism and denture demand.

PMID- 15555073
TI  - Male Reproductive Health: A village based study of camp attenders in rural India.
AB  - BACKGROUND: A paucity of information about male reproductive health and a
      perceived interest in involvement among local men provided the impetus for
      carrying out a village based male reproductive health camp. The aim was to
      investigate men's willingness to participate in such camps, and to describe
      reproductive health problems in men. METHODS: Structured interviews were carried
      out with 120 men attending a reproductive health check-up in a village in rural
      West Bengal, India. General information, details of family planning methods used
      and data on reproductive health complaints were collected. Clinical examinations
      were also carried out. Socio-demographic characteristics were compared for men
      with and without reproductive health and urinary complaints. RESULTS: Three
      quarters of the married men were using contraception, but the majority stated
      that their wives were responsible for it. The most common reproductive health
      complaint was urinary problems; 28% had burning on urination, and 22% reported
      frequent and/or difficult urination. There were few social or demographic
      differences between men with and without problems. Seventeen percent of the men
      had clinically diagnosed reproductive health problems, the most common being
      urethral discharge. None of the men with diagnosed problems were using condoms.
      CONCLUSIONS: This study highlights the interest of men in their reproductive
      health, but also highlights the high proportion of men with problems. In
      addition, a number of men with clinically diagnosed problems had not reported
      them in the interviews, illustrating either the reticence to report or the lack
      of knowledge about symptoms of reproductive health problems. Recommendations for
      future programmes and research in this field are given.

PMID- 15555074
TI  - Neuroanatomical organization of gonadotropin-releasing hormone neurons during the
      oestrus cycle in the ewe.
AB  - BACKGROUND: During the preovulatory surge of gonadotropin-releasing hormone
      (GnRH), a very large amount of the peptide is released in the hypothalamo
      hypophyseal portal blood for 24-36H00. To study whether this release is linked to
      a modification of the morphological organization of the GnRH-containing neurons,
      i.e. morphological plasticity, we conducted experiments in intact ewes at 4
      different times of the oestrous cycle (before the expected LH surge, during the
      LH surge, and on day 8 and day 15 of the subsequent luteal phase). The cycle
      stage was verified by determination of progesterone and LH concentrations in the
      peripheral blood samples collected prior to euthanasia. RESULTS: The distribution
      of GnRH-containing neurons throughout the preoptic area around the vascular organ
      of the lamina terminalis was studied following visualisation using
      immunohistochemistry. No difference was observed in the staining intensity for
      GnRH between the different groups. Clusters of GnRH-containing neurons (defined
      as 2 or more neurons being observed in close contact) were more numerous during
      the late follicular phase (43 +/- 7) than during the luteal phase (25 +/- 6), and
      the percentage of clusters was higher during the beginning of the follicular
      phase than during the luteal phase. There was no difference in the number of
      labelled neurons in each group. CONCLUSIONS: These results indicate that the
      morphological organization of the GnRH-containing neurons in ewes is modified
      during the follicular phase. This transitory re-organization may contribute to
      the putative synchronization of these neurons during the surge. The molecular
      signal inducing this plasticity has not yet been identified, but oestradiol might
      play an important role, since in sheep it is the only signal which initiates the
      GnRH preovulatory surge.

PMID- 15555075
TI  - The architecture of chicken chromosome territories changes during
      differentiation.
AB  - BACKGROUND: Between cell divisions the chromatin fiber of each chromosome is
      restricted to a subvolume of the interphase cell nucleus called chromosome
      territory. The internal organization of these chromosome territories is still
      largely unknown. RESULTS: We compared the large-scale chromatin structure of
      chromosome territories between several hematopoietic chicken cell types at
      various differentiation stages. Chromosome territories were labeled by
      fluorescence in situ hybridization in structurally preserved nuclei, recorded by
      confocal microscopy and evaluated visually and by quantitative image analysis.
      Chromosome territories in multipotent myeloid precursor cells appeared
      homogeneously stained and compact. The inactive lysozyme gene as well as the
      centromere of the lysozyme gene harboring chromosome located to the interior of
      the chromosome territory. In further differentiated cell types such as
      myeloblasts, macrophages and erythroblasts chromosome territories appeared
      increasingly diffuse, disaggregating to separable substructures. The lysozyme
      gene, which is gradually activated during the differentiation to activated
      macrophages, as well as the centromere were relocated increasingly to more
      external positions. CONCLUSIONS: Our results reveal a cell type specific
      constitution of chromosome territories. The data suggest that a repositioning of
      chromosomal loci during differentiation may be a consequence of general changes
      in chromosome territory morphology, not necessarily related to transcriptional
      changes.

PMID- 15555076
TI  - Susceptibility of different leukocyte cell types to Vaccinia virus infection.
AB  - BACKGROUND: Vaccinia virus, the prototype member of the family Poxviridae, was
      used extensively in the past as the Smallpox vaccine, and is currently considered
      as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide
      host range, and is known to infect cultures of a variety of cell lines of
      mammalian origin. However, little is known about the virus tropism in human
      leukocyte populations. We report here that various cell types within leukocyte
      populations have widely different susceptibility to infection with vaccinia
      virus. RESULTS: We have investigated the ability of vaccinia virus to infect
      human PBLs by using virus recombinants expressing green fluorescent protein
      (GFP), and monoclonal antibodies specific for PBL subpopulations. Flow cytometry
      allowed the identification of infected cells within the PBL mixture 1-5 hours
      after infection. Antibody labeling revealed that different cell populations had
      very different infection rates. Monocytes showed the highest percentage of
      infected cells, followed by B lymphocytes and NK cells. In contrast to those cell
      types, the rate of infection of T lymphocytes was low. Comparison of vaccinia
      virus strains WR and MVA showed that both strains infected efficiently the
      monocyte population, although producing different expression levels. Our results
      suggest that MVA was less efficient than WR in infecting NK cells and B
      lymphocytes. Overall, both WR and MVA consistently showed a strong preference for
      the infection of non-T cells. CONCLUSIONS: When infecting fresh human PBL
      preparations, vaccinia virus showed a strong bias towards the infection of
      monocytes, followed by B lymphocytes and NK cells. In contrast, very poor
      infection of T lymphocytes was detected. These finding may have important
      implications both in our understanding of poxvirus pathogenesis and in the
      development of improved smallpox vaccines.

PMID- 15555077
TI  - The measurement of health-related quality of life (QOL) in paediatric clinical
      trials: a systematic review.
AB  - BACKGROUND: The goal of much care in chronic childhood illness is to improve
      quality of life (QOL). However, surveys suggest QOL measures are not routinely
      included. In addition, there is little consensus about the quality of many QOL
      measures. OBJECTIVES: To determine the extent to which quality of life (QOL)
      measures are used in paediatric clinical trials and evaluate the quality of
      measures used. DESIGN: Systematic literature review. REVIEW METHODS: Included
      paediatric trials published in English between 1994 and 2003 involving children
      and adolescents up to the age of 20 years, and use of a standardised QOL measure.
      Data Sources included MEDLINE, CINAHL, EMB Reviews, AMED, BNI, PSYCHINFO, the
      Cochrane library, Internet, and reference lists from review articles. RESULTS: We
      identified 18 trials including assessment of QOL (4 Asthma, 4 Rhinitis, 2
      Dermatitis, and single studies of Eczema, Cystic fibrosis, Otis media, Amblyopia,
      Diabetes, Obesity associated with a brain tumour, Idiopathic short stature, and
      Congenital agranulocytosis). In three trials, parents rated their own QOL but not
      their child's. Fourteen different QOL measures were used but only two fulfilled
      our minimal defined criteria for quality. CONCLUSIONS: This review confirms
      previous reports of limited use of QOL measures in paediatric clinical trials.
      Our review provides information about availability and quality of measures which
      will be of especial value to trial developers.

PMID- 15555078
TI  - The biological effects of diagnostic cardiac imaging on chronically exposed
      physicians: the importance of being non-ionizing.
AB  - Ultrasounds and ionizing radiation are extensively used for diagnostic
      applications in the cardiology clinical practice. This paper reviewed the
      available information on occupational risk of the cardiologists who perform,
      every day, cardiac imaging procedures. At the moment, there are no consistent
      evidence that exposure to medical ultrasound is capable of inducing genetic
      effects, and representing a serious health hazard for clinical staff. In
      contrast, exposure to ionizing radiation may result in adverse health effect on
      clinical cardiologists. Although the current risk estimates are clouded by
      approximations and extrapolations, most data from cytogenetic studies have
      reported a detrimental effect on somatic DNA of professionally exposed personnel
      to chronic low doses of ionizing radiation. Since interventional cardiologists
      and electro-physiologists have the highest radiation exposure among health
      professionals, a major awareness is crucial for improving occupational
      protection. Furthermore, the use of a biological dosimeter could be a reliable
      tool for the risk quantification on an individual basis.

PMID- 15555079
TI  - The Menopause Rating Scale (MRS) as outcome measure for hormone treatment? A
      validation study.
AB  - BACKGROUND: The Menopause Rating Scale is a health-related Quality of Life scale
      developed in the early 1990s and step-by-step validated since then. No
      methodologically detailed work on the utility of the scale to assess health
      related changes after treatment was published before. METHOD: We analysed an
      open, uncontrolled post-marketing study with over 9000 women with pre- and post
      treatment data of the MRS scale to critically evaluate the capacity of the scale
      to measure the health-related effects of hormone treatment independent from the
      severity of complaints at baseline. RESULTS: The improvement of complaints during
      treatment relative to the baseline score was 36% in average. Patients with
      little/no complaints before therapy improved by 11%, those with mild complaints
      at entry by 32%, with moderate by 44%, and with severe symptoms by 55% - compared
      with the baseline score. We showed that the distribution of complaints in women
      before therapy returned to norm values after 6 months of hormone treatment. We
      also provided weak evidence that the MRS results may well predict the assessment
      of the treating physician. Limitations of the study, however, may have lead to
      overestimating the utility of the MRS scale as outcome measure. CONCLUSION: The
      MRS scale showed some evidence for its ability to measure treatment effects on
      quality of life across the full range of severity of complaints in aging women.
      This however needs confirmation in other and better-designed clinical/outcome
      studies.

PMID- 15555080
TI  - RNA interference: learning gene knock-down from cell physiology.
AB  - SUMMARY: Over the past decade RNA interference (RNAi) has emerged as a natural
      mechanism for silencing gene expression. This ancient cellular antiviral response
      can be exploited to allow specific inhibition of the function of any chosen
      target gene. RNAi is proving to be an invaluable research tool, allowing much
      more rapid characterization of the function of known genes. More importantly,
      RNAi technology considerably bolsters functional genomics to aid in the
      identification of novel genes involved in disease processes.This review briefly
      describes the molecular principles underlying the biology of RNAi phenomenon and
      discuss the main technical issues regarding optimization of RNAi experimental
      design.

PMID- 15555081
TI  - Discriminative topological features reveal biological network mechanisms.
AB  - BACKGROUND: Recent genomic and bioinformatic advances have motivated the
      development of numerous network models intending to describe graphs of
      biological, technological, and sociological origin. In most cases the success of
      a model has been evaluated by how well it reproduces a few key features of the
      real-world data, such as degree distributions, mean geodesic lengths, and
      clustering coefficients. Often pairs of models can reproduce these features with
      indistinguishable fidelity despite being generated by vastly different
      mechanisms. In such cases, these few target features are insufficient to
      distinguish which of the different models best describes real world networks of
      interest; moreover, it is not clear a priori that any of the presently-existing
      algorithms for network generation offers a predictive description of the networks
      inspiring them. RESULTS: We present a method to assess systematically which of a
      set of proposed network generation algorithms gives the most accurate description
      of a given biological network. To derive discriminative classifiers, we construct
      a mapping from the set of all graphs to a high-dimensional (in principle infinite
      dimensional) "word space". This map defines an input space for classification
      schemes which allow us to state unambiguously which models are most descriptive
      of a given network of interest. Our training sets include networks generated from
      17 models either drawn from the literature or introduced in this work. We show
      that different duplication-mutation schemes best describe the E. coli genetic
      network, the S. cerevisiae protein interaction network, and the C. elegans
      neuronal network, out of a set of network models including a linear preferential
      attachment model and a small-world model. CONCLUSIONS: Our method is a first step
      towards systematizing network models and assessing their predictability, and we
      anticipate its usefulness for a number of communities.

PMID- 15555083
TI  - Reconstruction of the pelvic ring using an autologous free non-vascularized
      fibula graft in a patient with benign fibrous histiocytoma.
AB  - BACKGROUND: Benign fibrous histiocytomas (BFH) usually presents as a small benign
      lesion that predominantly occurs in the skin. Only few cases of BFH arising from
      bone have been reported, its occurrence in pelvic bones is even rarer. CASE
      PRESENTATION: A 34-year-old female presented with BFH at a rare anatomical
      location on both sides of the os ilium which was larger than earlier reported BFH
      of the bone. Surgical resection was performed successfully including resection of
      the inner pelvic ring and reconstruction of the linea terminalis using a non
      vascularized fibular autograft. At 18 months after tumor resection and
      reconstruction of the pelvic ring, with interposition of a free vascularized
      fibula graft patient has an excellent clinical oncological and functional
      outcome. CONCLUSION: Non vascularized fibular autograft is a useful
      reconstructive procedure in select patients.

PMID- 15555082
TI  - Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion
      independent hexamer.
AB  - BACKGROUND: The enzyme porphobilinogen synthase (PBGS), which is central to the
      biosynthesis of heme, chlorophyll and cobalamins, has long been known to use a
      variety of metal ions and has recently been shown able to exist in two very
      different quaternary forms that are related to metal ion usage. This paper
      reports new information on the metal ion independence and quaternary structure of
      PBGS from the photosynthetic bacterium Rhodobacter capsulatus. RESULTS: The gene
      for R. capsulatus PBGS was amplified from genomic DNA and sequencing revealed
      errors in the sequence database. R. capsulatus PBGS was heterologously expressed
      in E. coli and purified to homogeneity. Analysis of an unusual phylogenetic
      variation in metal ion usage by PBGS enzymes predicts that R. capsulatus PBGS
      does not utilize metal ions such as Zn2+, or Mg2+, which have been shown to act
      in other PBGS at either catalytic or allosteric sites. Studies with these ions
      and chelators confirm the predictions. A broad pH optimum was determined to be
      independent of monovalent cations, approximately 8.5, and the Km value shows an
      acidic pKa of approximately 6. Because the metal ions of other PBGS affect the
      quaternary structure, gel permeation chromatography and analytical
      ultracentrifugation experiments were performed to examine the quaternary
      structure of metal ion independent R. capsulatus PBGS. The enzyme was found to be
      predominantly hexameric, in contrast with most other PBGS, which are octameric. A
      protein concentration dependence to the specific activity suggests that the
      hexameric R. capsulatus PBGS is very active and can dissociate to smaller, less
      active, species. A homology model of hexameric R. capsulatus PBGS is presented
      and discussed. CONCLUSION: The evidence presented in this paper supports the
      unusual position of the R. capsulatus PBGS as not requiring any metal ions for
      function. Unlike other wild-type PBGS, the R. capsulatus protein is a hexamer
      with an unusually high specific activity when compared to other octameric PBGS
      proteins.

PMID- 15555084
TI  - Sickle cell disease.

PMID- 15555085
TI  - Acute myocardial infarction.

PMID- 15555086
TI  - Angina (unstable).

PMID- 15555087
TI  - Atrial fibrillation (acute).

PMID- 15555088
TI  - Cardiovascular disorders. Changing behaviour.

PMID- 15555089
TI  - Cardiovascular disorders. Primary prevention.

PMID- 15555090
TI  - Secondary prevention of ischaemic cardiac events.

PMID- 15555091
TI  - Stroke prevention.

PMID- 15555092
TI  - Thromboembolism.

PMID- 15555093
TI  - Absence seizures in children.

PMID- 15555094
TI  - Bronchiolitis.

PMID- 15555095
TI  - Constipation in children.

PMID- 15555096
TI  - Gastroenteritis in children.

PMID- 15555097
TI  - Gastro-oesophageal reflux in children.

PMID- 15555098
TI  - Infantile colic.

PMID- 15555099
TI  - Migraine headache in children.

PMID- 15555100
TI  - Nosebleeds in children.

PMID- 15555101
TI  - Reducing pain during blood sampling in infants.

PMID- 15555102
TI  - Sudden infant death syndrome.

PMID- 15555103
TI  - Urinary tract infection in children.

PMID- 15555104
TI  - Appendicitis.

PMID- 15555105
TI  - Colorectal cancer.

PMID- 15555106
TI  - Helicobacter pylori infection.

PMID- 15555107
TI  - Stomach cancer.

PMID- 15555108
TI  - Acute sinusitis.

PMID- 15555109
TI  - Chronic suppurative otitis media.

PMID- 15555110
TI  - Otitis externa.

PMID- 15555111
TI  - Otitis media with effusion.

PMID- 15555112
TI  - Seasonal allergic rhinitis.

PMID- 15555113
TI  - Wax in ear.

PMID- 15555114
TI  - Foot ulcers and amputations in diabetes.

PMID- 15555115
TI  - Obesity.

PMID- 15555116
TI  - Prevention of cardiovascular events in diabetes.

PMID- 15555117
TI  - Primary hypothyroidism.

PMID- 15555118
TI  - Acute anterior uveitis.

PMID- 15555119
TI  - Age related macular degeneration.

PMID- 15555120
TI  - Bacterial conjunctivitis.

PMID- 15555121
TI  - Trachoma.

PMID- 15555122
TI  - HIV infection.

PMID- 15555123
TI  - HIV: prevention of opportunistic infections.

PMID- 15555124
TI  - Hepatitis B.

PMID- 15555125
TI  - Influenza.

PMID- 15555126
TI  - Leprosy.

PMID- 15555127
TI  - Lyme disease.

PMID- 15555128
TI  - Malaria: prevention in travellers.

PMID- 15555129
TI  - Meningococcal disease.

PMID- 15555130
TI  - Postherpetic neuralgia.

PMID- 15555131
TI  - Acute renal failure.

PMID- 15555132
TI  - Benign prostatic hyperplasia.

PMID- 15555133
TI  - Chronic prostatitis.

PMID- 15555134
TI  - Erectile dysfunction.

PMID- 15555135
TI  - Prostate cancer (metastatic).

PMID- 15555136
TI  - Prostate cancer (non-metastatic).

PMID- 15555137
TI  - Bipolar disorder.

PMID- 15555138
TI  - Bulimia nervosa.

PMID- 15555139
TI  - Deliberate self harm.

PMID- 15555140
TI  - Domestic violence.

PMID- 15555141
TI  - Obsessive compulsive disorder.

PMID- 15555142
TI  - Panic disorder.

PMID- 15555143
TI  - Schizophrenia.

PMID- 15555144
TI  - Acute gout.

PMID- 15555145
TI  - Ankle sprain.

PMID- 15555146
TI  - Bunions.

PMID- 15555147
TI  - Chronic fatigue syndrome.

PMID- 15555148
TI  - Fracture prevention in postmenopausal women.

PMID- 15555149
TI  - Herniated lumbar disc.

PMID- 15555150
TI  - Leg cramps.

PMID- 15555151
TI  - Low back pain and sciatica (acute).

PMID- 15555152
TI  - Low back pain and sciatica (chronic).

PMID- 15555153
TI  - Neck pain.

PMID- 15555154
TI  - Osteoarthritis.

PMID- 15555155
TI  - Plantar heel pain and fasciitis.

PMID- 15555156
TI  - Raynaud's (primary).

PMID- 15555157
TI  - Bell's palsy.

PMID- 15555158
TI  - Epilepsy.

PMID- 15555159
TI  - Headache (chronic tension-type).

PMID- 15555160
TI  - Migraine headache.

PMID- 15555161
TI  - Multiple sclerosis.

PMID- 15555162
TI  - Parkinson's disease.

PMID- 15555163
TI  - Trigeminal neuralgia.

PMID- 15555164
TI  - Aphthous ulcers (recurrent).

PMID- 15555165
TI  - Candidiasis (oropharyngeal).

PMID- 15555166
TI  - Halitosis.

PMID- 15555167
TI  - Postoperative pulmonary infections.

PMID- 15555168
TI  - Acute organophosphorus poisoning.

PMID- 15555169
TI  - Paracetamol (acetaminophen) poisoning.

PMID- 15555170
TI  - Nausea and vomiting in early pregnancy.

PMID- 15555171
TI  - Preterm birth.

PMID- 15555172
TI  - Acute bronchitis.

PMID- 15555173
TI  - Community acquired pneumonia.

PMID- 15555174
TI  - Spontaneous pneumothorax.

PMID- 15555175
TI  - Upper respiratory tract infection.

PMID- 15555176
TI  - Lung cancer.

PMID- 15555177
TI  - Bacterial vaginosis.

PMID- 15555178
TI  - Gonorrhoea.

PMID- 15555179
TI  - Partner notification.

PMID- 15555180
TI  - Pelvic inflammatory disease.

PMID- 15555181
TI  - Cellulitis and erysipelas.

PMID- 15555182
TI  - Head lice.

PMID- 15555183
TI  - Herpes labialis.

PMID- 15555184
TI  - Malignant melanoma (non-metastatic).

PMID- 15555185
TI  - Scabies.

PMID- 15555186
TI  - Squamous cell carcinoma of the skin (non-metastatic).

PMID- 15555187
TI  - Warts.

PMID- 15555188
TI  - Wrinkles.

PMID- 15555189
TI  - Sleep apnoea.

PMID- 15555190
TI  - Breast cancer (metastatic).

PMID- 15555191
TI  - Breast pain.

PMID- 15555192
TI  - Candidiasis (vulvovaginal).

PMID- 15555193
TI  - Dysmenorrhoea.

PMID- 15555194
TI  - Endometriosis.

PMID- 15555195
TI  - Menopausal symptoms.

PMID- 15555196
TI  - Menorrhagia.

PMID- 15555197
TI  - Ovarian cancer.

PMID- 15555198
TI  - Pyelonephritis in non-pregnant women.

PMID- 15555199
TI  - Recurrent cystitis in non-pregnant women.

PMID- 15555200
TI  - Venous leg ulcers.

PMID- 15555201
TI  - Ethnic differences in body mass index and associated factors of adolescents from
      minorities in Oslo, Norway: a cross-sectional study.
AB  - OBJECTIVES: To examine ethnic differences in body mass index (BMI), food habits
      and physical activity, and determine the factors contributing to differences in
      BMI. DESIGN AND METHOD: In 2000-2001, 7343 (response rate 88%) 15- and 16-year
      old students, enrolled in lower secondary schools in Oslo, participated in the
      cross-sectional Oslo Health Study. Of these participants, 1719 were defined as
      ethnic minorities. RESULTS: Significant gender and ethnic differences in mean BMI
      were observed. Of the ethnic minority adolescents, 5.8% were underweight (<5th
      percentile of the US Centers for Disease Control and Prevention (CDC)/National
      Center for Health Statistics (NCHS) reference distribution) and 9.1% were
      overweight (>85th percentile of the US CDC/NCHS reference distribution). BMI was
      not significantly associated with either socio-economic factors or physical
      activity. Food habits and physical activity differed with ethnicity but not with
      socio-economic factors. An ordinal regression showed that girls from East Asia
      (odds ratio (OR) 0.4) and boys from sub-Saharan Africa (OR 0.4) had lower BMI
      than the Western group. Among girls, higher BMI was associated with less frequent
      consumption of chocolates and sweets, full-fat milk and breakfast (OR 2.4, 1.7
      and 1.7, respectively). Higher BMI, for both boys and girls, was associated with
      current and past dieting (OR 3.7 and 4.2, respectively). CONCLUSIONS: Adolescent
      food habits and physical activity varied by gender and ethnicity but not with
      socio-economic factors. BMI was associated with ethnicity, gender and food
      habits, but no significant relationship was observed with socio-economic factors
      or physical activity. Ethnicity, in addition to gender, should be taken into
      consideration when studying BMI and associated factors among adolescents.

PMID- 15555202
TI  - Adjuvant therapy: new treatment options.

PMID- 15555203
TI  - Intergroup trial fails to demonstrate a benefit with the addition of irinotecan
      to bolus 5-fluorouracil/leucovorin in stage III colon cancer.

PMID- 15555204
TI  - Surgical issues in rectal cancer: a 2004 update.
AB  - Rectal cancer is a major health concern in the United States, with an estimated
      40,570 new cases diagnosed in 2004. There are 4 major goals in the treatment of a
      patient with rectal cancer: local control; long-term survival; preservation of
      anal sphincter, bladder, and sexual function; and maintenance or improvement in
      quality of life. Recent advances have been made in preoperative staging, local
      and radical surgical therapy, the importance of distal and circumferential
      resection margins, postoperative preservation of the anal sphincter mechanism and
      genitourinary function, and the role of laparoscopy in the treatment of these
      patients. Our aim is to outline some of the important surgical issues surrounding
      the management of patients with early-stage (T1/T2 N0) or locally advanced (T3/T4
      and/or N1) rectal cancer.

PMID- 15555205
TI  - Small bowel adenocarcinoma: a rare but aggressive disease.
AB  - Unlike the colon and rectum, the small intestine is associated with a very low
      rate of tumor occurrence. Adenocarcinomas represent the most frequent of these
      rare digestive tumors and are often fatal as a result of tardy diagnosis.
      Regardless of the stage, surgery usually remains the cornerstone of small bowel
      adenocarcinoma therapy. Because of the rarity of the disease, very few
      significant clinical trials have identified any efficient nonsurgical treatment;
      however, recent data indicate these tumors might be sensitive to chemotherapy
      alone or in association with radiation therapy. Conversely, a great deal of
      progress has been achieved in diagnosis of the tumor, whether by adaptation of
      existing techniques or development of new ones. We reviewed the clinical aspects
      of this rare but aggressive disease, focusing on new diagnostic procedures as
      well as on recent advances in their therapeutic management.

PMID- 15555207
TI  - Genetic alterations in locally advanced stage II/III colon cancer: a search for
      prognostic markers.
AB  - Heterogeneity in advanced colon cancer leads to different results from adjuvant
      chemotherapy. To identify groups of patients who may need adjuvant treatment,
      molecular staging and correlation with clinical data may be helpful in
      classifying histologically similar tumors. Colon cancer develops through a
      multistep process with an accumulation of multiple genetic alterations that are
      often the cause of a form of genomic instability. The 2 best known mechanisms of
      genomic instability are chromosomal instability (CIN) and microsatellite
      instability (MSI). The CIN phenotype is found in approximately 85% of sporadic
      colon cancers and is characterized by aneuploidy, multiple chromosomal
      rearrangements, and an accumulation of somatic mutations in oncogenes such as K
      ras and tumor suppressor genes such as TP53 and APC. The MSI phenotype is
      associated with small insertions and deletions mainly in repetitive sequences
      (microsatellites) and is found in approximately 15% of cases. This instability,
      often referred to as high-frequency MSI (MSI-H), is caused by defects of the
      mismatch repair system, which is involved in repairing DNA errors that arise
      during DNA replication. Clear-cut correlations between the somatic genetic
      alterations in tumors and the clinical behavior of the tumor are rare. Only a few
      markers, such as MSI-H and TP53, seem to have a prognostic value. Mutations in
      the TP53 gene are associated with an aggressive tumor growth and subsequent
      reduced survival, whereas MSI-H seems to be correlated with a favorable outcome.
      In general, predicting biologic behavior of in particular stage III colon cancers
      is difficult and remains a great clinical problem.

PMID- 15555208
TI  - Genetic determinants in the study of colorectal cancer.

PMID- 15555209
TI  - Expression of vascular endothelial growth factor and HER2/neu in stage II colon
      cancer and correlation with survival.
AB  - Monoclonal antibody-directed therapy has been used as an effective treatment for
      some cancers that overexpress HER2/neu and vascular endothelial growth factor
      (VEGF). Overexpression of the HER2/neu oncogene and VEGF has been reported to
      occur in adenocarcinomas of the colon. Assessing whether HER2/neu and VEGF
      overexpression could serve as prognostic indicators for stage II colon cancer may
      provide insight into optimal treatment following surgery. Demographic and tumor
      characteristics from 109 patients diagnosed with stage II colon cancer between
      1991 and 1996 were assessed for HER2/neu and VEGF expression using
      immunohistochemical staining techniques. Of the 109 cases, 107 (98%) were
      histologically classified as adenocarcinomas, 105 (96%) were grades 2/3, and 105
      (96%) were stage T3. Only 12 cases (11%) exhibited HER2/neu overexpression and 72
      cases (66%) exhibited VEGF expression. There was no significant difference in
      overall survival or in time to recurrence between the groups with and without
      HER2/neu overexpression. There was a trend toward decreased overall survival with
      VEGF expression (P = 0.07), but no difference in time to recurrence (P = 0.63).
      There were 18 patients who received adjuvant chemotherapy, but removal of these
      patients from the analysis did not change the results. There was no association
      between HER2/neu and VEGF expression and patient demographics or tumor
      characteristics, with the exception of VEGF expression and mucinous histology (P
      < 0.01). Our results do not support an association between HER2/neu or VEGF
      expression and overall survival or time to recurrence in stage II colon cancer.
      With further investigation, a significant correlation may be found between VEGF
      expression and prognosis, and thus direct therapy with a monoclonal antibody.

PMID- 15555210
TI  - A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer.
AB  - This phase II study was designed to characterize the clinical activity of ISIS
      3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with
      pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were
      given a dose of 2.0 mg/kg per day, and 5 patients received 3.0 mg/kg per day
      given over 21 days followed by a 7-day rest period. Patients continued with study
      until evidence of disease progression or unacceptable toxicity was detected.
      Patients underwent baseline tumor biopsies followed by a second biopsy during the
      last week of the first 21-day infusion. All 16 patients underwent baseline tumor
      biopsies, and 12 of the 16 patients underwent on-study tumor biopsies. No
      evidence of tumor response was observed. One patient had stable disease after 2
      cycles and remained on for 1 additional cycle only to demonstrate progression of
      disease at that time. No dose-limiting or other significant toxicities were
      observed at both dosages, which could not be explained by progression of disease.
      Fatigue was common in all patients treated but was not dose limiting, and there
      was no evidence of coagulopathy. Analysis of the tumor biopsies obtained from the
      11 evaluable samples showed marked uptake of ISIS 3521 in the normal liver
      parenchyma. However, there was minimal uptake within the tumor cells. In
      addition, no evidence of any alteration in protein kinase C-a within the tumors
      or any downstream effects leading to apoptosis were observed. ISIS 3521
      demonstrated no clinical activity or target modulation in refractory metastatic
      CRC.

PMID- 15555211
TI  - High-throughput gene sequencing assay development for hereditary nonpolyposis
      colon cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary
      colon cancer syndrome and is responsible for as many as 10% of all colorectal
      cancers. Hereditary nonpolyposis colorectal cancer is autosomally dominant with a
      prevalence of 1 in 200-2000 and exhibits incomplete penetrance. Affected
      individuals have an approximately 70% lifetime risk of colon cancer with a mean
      age of onset of 44 years and an approximately 40% lifetime risk of endometrial
      cancer. At least 5 mismatch repair genes (MLH1, MSH2, MSH6, PMS1, PMS2) have been
      implicated in HNPCC; however, no predominant mutations were found in these genes.
      Mutation detection by direct sequencing has proven to be the most sensitive
      method. We have developed high-throughput full-length sequencing assays of the
      MLH1, MSH2, and MSH6 genes. These 3 genes account for approximately 90% of all
      germline mutations found in HNPCC. In our assays, 19 exons of MLH1, 16 exons of
      MSH2, 10 exons of MSH6, and the adjacent splice sites were amplified using
      polymerase chain reaction and loaded onto a capillary sequencing machine. Results
      were analyzed using sequence analysis software and stored in a relational
      database. Our assay method was validated using 15 affected patients and normal
      controls. It is anticipated that our high-throughput assay technique will provide
      accurate diagnoses for patients at risk for HNPCC and thereby facilitate early
      curative intervention.

PMID- 15555212
TI  - Combining targeted agents in lung cancer.

PMID- 15555213
TI  - Activity of bortezomib in advanced non-small-cell lung cancer.

PMID- 15555214
TI  - Emerging molecular biomarkers for early detection of lung cancer in patients at
      high risk.

PMID- 15555215
TI  - Radiofrequency ablation: identification of the ideal patient.
AB  - Radiofrequency (RF) ablation (RFA) is a relatively new modality that is being
      used for lung tumors with increasing frequency. Radiofrequency energy consists of
      an alternating current that moves from an active electrode that is placed within
      the tumor to dispersive electrodes that are placed on the patient. As the RF
      energy is applied, frictional heating of tissues results, with cell death
      occurring at temperatures > 60 degrees C. This article discusses preclinical and
      early clinical experience with RFA for lung tumors. Radiofrequency ablation has
      been used for patients with primary lung cancer and limited pulmonary metastases.
      Current data suggest that RFA is most suitable for tumors < or = 4 cm in size and
      is better for peripheral rather than centrally based nodules. Additionally,
      studies of RFA followed by resection have demonstrated a learning-curve effect
      with improved tumor kill in the later cases performed in these series. Surgical
      resection should continue to be the primary modality offered to patients with
      early-stage non-small-cell lung cancer and limited metastatic disease to the
      lungs (when the primary tumor is controlled). Radiofrequency ablation is a good
      option for those patients who are believed to be at increased risk for resection
      or who refuse resection, when operation would otherwise be appropriate therapy.
      Additionally, RFA may be used for local control of peripheral tumors in patients
      with more advanced cancers in combination with other therapies.

PMID- 15555216
TI  - Therapeutic advances in second-line treatment of advanced non-small-cell lung
      cancer.
AB  - A majority of patients with lung cancer present with advanced disease:
      approximately 30% with locally advanced disease and 45% with metastatic disease.
      The prognosis for these patients is poor, with 5-year survival rates ranging from
      5% to 15% for stage IIIB disease and < 5% for stage IV disease. For patients
      confronting advanced disease, chemotherapy is an essential option for disease
      control and palliation. Although a number of effective first-line regimens exist,
      virtually all patients with advanced non-small-cell lung cancer (NSCLC) will have
      disease relapse. For these patients, identifying the optimal treatment course
      remains a challenge. This article reviews approved and investigational second
      line therapeutic options in patients with relapsed advanced NSCLC. Recently,
      docetaxel has been shown to improve survival in patients with advanced NSCLC who
      had progressive disease following treatment with platinum-containing
      chemotherapy. Subsequently, permetrexed was compared with docetaxel in a second
      line treatment study that showed survival for both patient groups was virtually
      identical. Recently, erlotinib was associated with significantly longer survival
      compared with best supportive care in the second- or third-line treatment
      settings. Salvage treatment for NSCLC is reviewed, and the relative merits of the
      currently available treatments as well as agents that are pending Food and Drug
      Administration approval as second-line treatments are discussed.

PMID- 15555217
TI  - Adjuvant therapy of resected non-small-cell lung cancer.
AB  - Surgical resection of early-stage non-small-cell lung cancer (NSCLC) remains the
      standard of care in patients fit for surgery. Careful preoperative staging is
      imperative, as is pathologic documentation of the mediastinal nodal contents.
      Adjuvant postoperative thoracic radiation therapy (RT) clearly has an impact in
      reducing locoregional recurrence but has no clear impact on survival. The
      Postoperative RT (PORT) metaanalysis raised concerns about PORT, particularly in
      stage I/II NSCLC, suggesting it may negatively impact survival. This was not a
      concern in stage III NSCLC, in which the risk of locoregional recurrence is
      higher. However, distant recurrence remains the dominant pattern in resected
      NSCLC, suggesting that the majority of patients with early-stage resected NSCLC
      harbor occult micrometastatic disease. Historically, the role of adjuvant
      chemotherapy has been controversial, and its routine use was not supported by the
      published data, which consisted of a small number of underpowered trials using
      inadequately delivered, antiquated chemotherapy. More recently, larger trials
      have been reported with conflicting results. Like adjuvant PORT, chemotherapy
      combined with RT has not improved survival over PORT alone. The use of adjuvant
      cisplatin-based therapy did not show a survival advantage in the Adjuvant Lung
      Project Italy study but did in the International Adjuvant Lung Trial, creating
      controversy in the routine implementation of adjuvant therapy in all patients.
      Recently completed randomized trials by the Cancer and Leukemia Group B and the
      National Cancer Institute of Canada provide convincing evidence of a substantial
      benefit from adjuvant therapy in well-staged and completely resected stage I/II
      NSCLC. Currently, the totality of the data supports a discussion with patients
      with resected NSCLC regarding the potential benefits of adjuvant therapy.

PMID- 15555218
TI  - Clinical benefit of zoledronic acid in patients with lung cancer and other solid
      tumors: analysis based on history of skeletal complications.
AB  - The results of a retrospective exploratory analysis of a phase III trial of
      zoledronic acid in patients with bone metastases secondary to lung cancer or
      other solid tumors are reported herein to assess the risk of skeletal-related
      events (SREs) and the efficacy of 4 mg zoledronic acid compared with placebo. The
      study is based on patient SRE history before study entry. Patients were
      stratified based on SRE history (eg, pathologic fracture, spinal cord
      compression, radiation therapy or surgery to bone, or hypercalcemia) before study
      entry, and SRE incidence over 21 months was analyzed. Of 507 patients randomized
      to 4 mg zoledronic acid or placebo, 131 completed the 9-month core phase and 69
      entered the 12-month extension phase. Before study entry, 347 of 503 patients who
      were evaluable for efficacy (69%) experienced >/= 1 SRE; these patients had a
      higher risk of developing an SRE on study than patients with no prior SRE (odds
      ratio, 1.41). Among patients with an SRE before study entry, zoledronic acid
      reduced the risk of SREs by 31% (P = 0.009), reduced the mean skeletal morbidity
      rate (1.96 vs. 2.81 SREs per year for placebo; P = 0.030), and prolonged the
      median time to first SRE by nearly 4 months (215 days vs. 106 days for placebo; P
      = 0.011). Among patients with no SRE before study entry (n = 156), zoledronic
      acid reduced the risk of SREs by 23% (P = 0.308), reduced the mean skeletal
      morbidity rate (1.34 vs. 2.53 SREs per year for placebo; P = 0.332), and
      prolonged the median time to first SRE by 2.5 months (P = 0.534). This
      exploratory analysis demonstrates that patients with a history of SREs are at
      high risk for subsequent SREs, but zoledronic acid reduces skeletal morbidity
      regardless of SRE history.

PMID- 15555219
TI  - Prospective randomized phase III trial of etoposide/cisplatin versus high-dose
      epirubicin/cisplatin in small-cell lung cancer.
AB  - High-dose epirubicin plus cisplatin was compared with the reference regimen of
      etoposide/cisplatin in small-cell lung cancer (SCLC). Four hundred two previously
      untreated patients with SCLC were randomized to receive etoposide 100 mg/m(2) on
      days 1-3 and cisplatin 100 mg/m(2) on day 1 or epirubicin 100 mg/m(2) and
      cisplatin 100 mg/m(2) on day 1 every 21 days for a total of 6 cycles. Patients
      were stratified according to treatment center and extent of disease (limited
      disease, n = 207; extensive disease, n = 195). Patients with limited disease were
      treated with thoracic radiation therapy after completion of chemotherapy, and
      those who exhibited a complete response were advised to receive prophylactic
      cranial irradiation. The primary endpoint was survival, and secondary endpoints
      were time to progression (TTP), response, toxicity, and costs. Patient
      characteristics were generally well balanced in the 2 arms, even though more
      patients in the epirubicin/cisplatin arm had > 5% weight loss and poor Karnofsky
      performance index compared with the etoposide/cisplatin arm. One hundred thirty
      four patients (66.3%) in the etoposide/cisplatin arm and 126 (63.0%) in the
      epirubicin/cisplatin arm received all 6 planned cycles of chemotherapy. Response
      rate, TTP, and survival did not differ significantly between the 2 arms. Grade
      3/4 neutropenia and toxic deaths occurred more frequently in the
      etoposide/cisplatin arm. Epirubicin/cisplatin showed a similar activity with a
      slightly lower toxicity profile than the reference regimen of
      etoposide/cisplatin. The epirubicin/cisplatin regimen may be recommended in the
      treatment of SCLC.

PMID- 15555220
TI  - Expression levels of protein kinase C-alpha in non-small-cell lung cancer.
AB  - Current treatments of non-small-cell lung cancer (NSCLC) are inadequate and new
      therapies are being developed that target specific cellular signaling proteins
      associated with tumor growth. One potential target is protein kinase C (PKC)
      alpha, a signaling molecule with an important role in cell regulation and
      proliferation. The present study examines the expression levels of PKC-alpha in
      NSCLC to better understand the distribution of PKC-alpha in NSCLC. We analyzed
      tumor specimens from an independent tumor tissue bank to determine PKC-alpha
      protein and messenger RNA gene expression in NSCLC. In addition, we used publicly
      available gene expression array data to further understand PKC-a-associated gene
      expression profiles in NSCLC. We found that PKC-alpha is highly expressed in < or
      = 20% of patients with NSCLC. We also found that PKC-alpha was preferentially
      expressed in adenocarcinoma compared with squamous cell carcinoma of the lung.

PMID- 15555221
TI  - [Stressing the practice of basic training in the studies of the art of history of
      medicine].

PMID- 15555222
TI  - [Experiences of prevention and treatment of infectious diseases in Chinese Soviet
      Republic].
AB  - Many kinds of infectious diseases had been prevalent during the Chinese Soviet
      Republic period. Experiences were accumulated during the fighting against these
      diseases, and high attention paid by the government including the party, the
      military and the administration, and strengthening of legislation for prevention
      and treatment works, with the Red Army as the main task force for the work, and
      the great mass actively involved in this work, with active propaganda for its
      prevention and treatment.

PMID- 15555223
TI  - [On the epidemic, prevention and treatment of Kala-Azar in northern Jiangsu in
      1930s].
AB  - In the 1930s, the Kala-Azar spread rapidly and widely in 16 counties of northern
      Jiangsu, with infected victims amounted to 30,0000, yielding great damage to the
      society. The government of the Republic of China did strive for its prerention
      and treatment. Under whose guidance, there were Huaiyin Investigating Team for
      Kala-Azar and Prevention and Treatment Team of Huaiyin region for Kala-Azar with
      rather satisfactory results. However, the final outcome was poor because of
      bewilderment at epidemic way, deficiency of funds, underdeveloped economics and
      sanitation in the rural areas, the poor income of peasantry and faults in
      national preventing epidemic system, etc.

PMID- 15555224
TI  - [Investigation on the historical facts about Zhu Weiju, a modern famous
      physician].
AB  - Zhu Weiju (1884 - 1951) was born to a physician family and read extensively
      medical books of all ages. He entered a military medical school to learn western
      medicine and investigated western medicine in Japan when he was young. He
      advocated to reform traditional Chinese medicine (TCM) by incorporating
      scientific knowledge and created a theory of "Five section-Eight guideline" to
      elucidate Zhongjing's theory. He got a nickname "Zhu-aconitum" due to his favor
      on using aconitum. He practiced medicine in Shanghai in his middle age and ran
      medical schools. He challenged the Warm-disease School in Shanghai, which
      advocated the application of "clear-light atmosphere" by applying heavy warm and
      hot medicines to save critical cases, and was famous of his applying warm-hot
      remedies as the "Zhu's School" at a time in Shanghai. His academic thought was
      focused in his representative work, Shang han zhi nan (Questioning in Cold
      Pathogenic Diseases). His disciples include Chen Susheng, Xu Zhongcai and Wang
      Zhaoji.

PMID- 15555225
TI  - [Textual research on the author of Ji feng pu ji fang (Jifeng's Formularies for
      universal relief)].
AB  - As a medical book of the Song dynasty, there are marks of "re-collating and
      checking" at the head of each subject at each volume in Ji feng pu ji fang
      (Jifeng's Formularies for Universal Relief), thus, the book was mistakenly
      attributed to Zhang Rui. Based on the time characteristics, case records, medical
      affairs, avoidance of emperor's name, and the original draft, it should be
      written during the Yuanfeng reign and published during the Gaozong emperor of the
      Southern Song dynasty. By carefully analyzing the medical lives of Sun Zhao, who
      died at the end of Yuanfeng reign, Sun Zhao should be its real author, whereas
      Zhang Rui, who was still alive in the Shaoxing reign of the Southern Song
      dynasty, was not its author. The research into the medical affairs and birth date
      of Chu Yushi and Dong Ji's Jiao qi zhi fa zong yao (Essential for Treating
      Beriberi) provides a powerful evidence for this conclusion.

PMID- 15555226
TI  - [Connotation of channel and its relation with nerve].
AB  - Originated for the recognition on the anatomy and physiology of "vessel", the
      theory of channel treats the running pathway of the vessel as jing mai (channel
      vessel), with its transverse branches as mai (vessel), thus the idea of jing luo
      and jing mai was gradually formed and the connotation of "channel (jing luo)" is
      with the etymological connotation of function of the nerve. The challenge to
      channel theory comes from the introduction of western medicine, or in other
      words, people interpret the communication among the body surface and the upper
      and lower parts of the surface, the special connection between the body surface
      and the internal organs, the adjusting and reaction function. During the
      introduction of western anatomy-physiology in the late Ming dynasty or the
      eastward introduction of western medical science at the late Qing dynasty, the
      terms of traditional Chinese medicine (TCM) connected with channel functions,
      including "minute tendon (xi jin)", "connection (xi)" had been rendered as the
      Chinese translation of "nerve". Thus, the language transforming basis between
      channel and nerve function was laid down at the first stage of confluence between
      TCM and western medicine.

PMID- 15555227
TI  - [A brief history of treatment based on differential diagnosis of Zheng].

PMID- 15555228
TI  - [A new study on the life of Mongolian physician Zhanbra Dorje].

PMID- 15555229
TI  - [History of surgery for breast cancer].

PMID- 15555230
TI  - [The evolvement of the theory of dental implant-bone interface].

PMID- 15555231
TI  - [Brief textual research on Zhu Duanzhang and his Weisheng Jiabao serial
      formularies].

PMID- 15555232
TI  - [A brief developmental history of studies on cell cycle and cell cycle control].

PMID- 15555233
TI  - [A study on the Menghe medical sect].
AB  - From the late Ming to modern age, famous physicians in Menghe came forth in large
      numbers, contributing to the formation of the Menghe scholarly sect with the four
      families of the Fei, Ma, Chao, and Ding as its representatives, featuring erudite
      academic knowledge, rich clinical experiences with distinguished contributions to
      the development of TCM. The materials presented in this article include
      investigation from over 100 kinds of genealogies, works of the Menghe sect
      collected from over 100 works written by the Menghe physicians, local chronicles,
      family tree collected in all major libraries in China and those in Europe, the
      US, Hong Kong and Taiwan, as well as through interviews with over 200 persons,
      including descendants of the Menghe sect, physicians related to the sect. Like a
      shinning star, the Menghe sect illuminated the medical province during the late
      Qing dynasty and early republican periods and even today as well.

PMID- 15555234
TI  - [Investigation on Qiantang medical school].
AB  - Qiantang medical school came into being during the late Ming Dynasty and the
      early Qing Dynasty, and lasted for 200 years until Guang Xu Reign in the late
      Qing Dynasty. Lu Zhiyi and Zhang Suichen were the early representative figures;
      Zhang Zhicong, Zhang Xiju and Gao Shizong were the mid-period representative
      figures; and Zhong Xuelu was the late representative figure. They respected
      consistently the classics and the ancients, cultivated new talents, studied
      medical literature with a trinity of teaching, studying the classics and
      practising medicine as its characteristic. Eventually, it developed under the
      specific background of time and geographical environment as the only academic
      medical school enbodying teaching, studying the classics, and medical practice as
      a whole with distinguished achievements.

PMID- 15555235
TI  - [A brief history of prevention and treatment of diphtheria in modern TCM].
AB  - During this 200 years, traditional medical professionals had paid high attention
      to diphtheria, an epidemic disease, and had underwent a whole understanding
      process from the initial stage to active and gradual improvement of diagnosis,
      prevention, and treatment etc. Many physicians summarized a series of effective
      treatment, defined "nourishing yin and clearing the lung (Yong Yin Qing Fei)" as
      basic principle, with Yang Yin Qing Fei Decoction as a specific prescription
      exclusively applied for diphtheria and obtained considerable curative effect. TCM
      did make contributions to its prevention and treatment before effective treatment
      in biomedicine appeared in China. Meanwhile, the measures and experiences was a
      great innovation in modern TCM and provided valuable experiences for conquering
      epidemic diseases.

PMID- 15555236
TI  - [A brief history of diagnosis and treatment of primary aldosteronism.].
AB  - Primary aldosteronism is a clinical syndrome characterized by hypokalemia,
      suppressed activities of plasma renin and high urinary and plasma aldosterone
      levels in hypertensive patients. It was first defined and reported by Jerome W.
      Conn in 1955. From 1960s to early 1970s, its techniques of diagnosis and
      treatment were greatly improved by the availability of spironolactone,
      realization of the renin-angiotensin-aldosterone system, and progress in
      laboratory tests and adrenal venous sampling. In 1970s, notwithstanding the
      extensive application of modern imaging modalities, such as CT scanning, adrenal
      venous sampling and steroid analysis have remained to be the most accurate and
      reliable localization method. From 1980s, more and more patients with primary
      aldosteronism were screened out from the hypertensive population by plasma renin
      activity/plasma aldosterone concentration ratio and cured by surgical
      interventions; laparoscopic unilateral adrenalectomy has become the generally
      accepted golden standard of operation.

PMID- 15555237
TI  - [A discussion on influence of philosophical idea of Guan Zi on TCM].
AB  - Guan Zi has substantial content and deep idea, being paid great attention among
      the various ancient schools of thought. After discussing the influence of its
      philosophical idea on TCM, it can be concluded that Guan Zi raised Yin Yan
      concept to a natural law earlier after Lao Zi first philosophized it. Meanwhile
      discussed the relationship between Yin and Yang systematically such as respecting
      Yang, Yang can control Yin, and relativity of Yin and Yang. It first setup Jing 
      Qi Theory, discussing materiality of the Nature and life from the sense of
      ontology. But it confused Jing Shen and Jing Qi, and could not weep the primitive
      color of Xing-Shen Monism. It emphasized on self-cultivation and embodied Xu
      (voidness), Yi (unity), Jing (tranquility) and Yin (cause) on preserving health.

PMID- 15555238
TI  - [Influence of climatic factor on formation and development of TCM].
AB  - Climatic factors influence health, physiological and pathological condition of
      human being, and then influence medicine. Through discussing the relationship
      between climatic type and traditional Chinese medical theory, relationship
      between climatic changes and formation and development of Cold-Warm School, and
      regional characteristic of Ling Nan medicine, conclusion can be made: firstly,
      traditional Chinese medical theory has some regional limit because its formation
      was influenced by climatic factor; secondly, climatic changes in history is the
      important cause leading to formation and vicissitude of Cold-Warm School in TCM
      history; thirdly, as an important branch of TCM, Ling Nan medicine reflects its
      own climatic characteristic and shows good adaptability and promising prospects
      of TCM.

PMID- 15555239
TI  - [Ye shes dpal'byor and Gan lu si bu (The four Tantras of nectar)].
AB  - Yeshes Palbyor was born in Haiyan County, Qinghai Province in 1704. As a
      youngster he studied medicine, Buddhism and linguistics in Ta'er Monastery. At
      the age of 28, he returned to Gunglung Monastery in his home town until his
      death. He devoted his whole life to the study of clinical therapeutics and
      Mongolian medicine. Gan lu si bu was his representative work, in which he
      advanced the theory of Six Basic Syndromes and Chills and Fever.

PMID- 15555240
TI  - [Colleagues Association: A medical organization in modern Japan].
AB  - Colleagues Association was established in Tokyo, Japan in June, 1902 as a
      professional medical group aiming at the spread of advanced Japanese medical
      science in China and to other neighboring countries. Until February 1946, it
      carried out many medical activities such as opening hospitals and publishing
      journals for over four decades. It flaunted the banner of medical spread and
      exchange, but on the other hand, it provided Japanese army with medical service
      and facilities and resisted European and American medical activities after being
      supervised by the Japanese government with the aggression against China. So it
      changed into a medical organization to assist the Japanese government to invade
      Asia.

PMID- 15555241
TI  - [The influence of Beijing TCM society on the development of TCM in Beijing].
AB  - Being a medical institution with the longest history and most influential TCM
      academic group, Beijing TCM Learned Society had a 3-stage history in Beijing
      area. in the Republican period of China in the 1920s, it was set up and organized
      by the imperial physicians and compiled History of Imperial Physicians in the
      Qing Dynasty and Yi Tong Zheng Mai (Orthodox Medical Heritage). In the 1930s, the
      number of its members and achievements reach its zenith. It started to publish
      China Medical Monthly, compiled many TCM books and extended its influence
      nationwide. In the 1940s, it was renamed China Medicine Research Association,
      then joined the International Science Organization. After that it held many
      academic activities and exchanged many valuable articles. These three phases
      promoted the development of TCM in Beijing in varying degrees.

PMID- 15555242
TI  - [A brief textual research on the editions of Fu Ren Liang Fang (A complete book
      of effective prescriptions for women) before the Qing Dynasty].
AB  - Fu Ren Liang Fang (A Complete Book of Effective Prescriptions for Women), the
      first complete gynecologic and obstetric work in China, was written by Cheng Zi
      ming in the first year of Jiaxi Reign of the Southern Song Dynasty (A.D.1237). It
      has many different editions in its long circulation of more than 760 years.
      According to The National Associated Catalog of TCM Books, it is estimated that
      there are as many as over 30 different editions. After choosing the edition of
      Qingyou Hall of the Yuan Dynasty as the original edition for comparisons with
      other editions, it is claimed that the edition of this Qingyou Hall was well
      preserved, with excellent and clear handwriting, reflecting the style and
      features of Chen's original work.

PMID- 15555243
TI  - [Developments of research on "qiu shi" (autumn stone)].

PMID- 15555244
TI  - [Research on mutual collation between Japan Cabinet Edition and National Beijing
      Library Edition of Shang han lun (Treatise on Cold Pathogenic Disease)].
AB  - Through textual research on the Song Dynasty block-printed large-character and
      small-character editions of Shang han lun (Treatise on Cold Pathogenic Disease),
      it can be definitely verified that Yang Shoujing's so-called 'facsimile
      handwritten copy of Northern Song edition' was an apocrypha fabricated by Yang
      himself. Japanese Horikawa's An zheng edition, the original edition adopted by
      Yun Tieqiao's photocopy, did exert a profound and lasting influence on China.
      After collating the Song Dynasty block-printed edition collected in Japan
      National Cabinet Library with the one collected in the National Beijing Library
      thoroughly, and checking the prefaces and postscripts carefully, it has been
      found, for the first time, that these two editions, both called 'Song edition',
      differ dramatically.

PMID- 15555245
TI  - [The wax and wane of the trend of "man benefits man" in the late Ming Dynasty].
AB  - It was in the period of from Jia Jing to Wan Li Reign that the trend of
      medication of "man benefits man" appeared with rather great influence in the
      society. This medication trend experienced a process of rising, zenith,
      declining, and eventual termination. Among this trend, the refining process of
      Hong Qian (Red Lead) and Pan Tao Jiu (Mythical Peach Alcohol) was imbued with the
      ruin of women, arousing debate soon after the trend appeared, with a tit for tat
      struggle between two medical schools. This research reveals that such medication
      trend is an adverse current started by fallacious alchemists. Its influence goes
      beyond the scope of medical field, though its position in the medical province
      itself is rather low.

PMID- 15555246
TI  - [The historical condition in the spread of Sanqi (Panax notoginseng) in the Ming
      Dynasty].
AB  - A well-known and extensively applied Chinese herbs for promoting blood
      circulation and resolving blood stasis, San qi (Pana Notoginseng) is one of the
      medicinal plants first applied by the minority ethnic groups in southwestern
      China originally grown in Wenshan of Yunnan and Baise of Guangxi, China. The
      doctors in inland China began to know and apply it in the Ming Dynasty,
      indicating that the spread of medicine is restricted and influenced not only by
      geographical positions but also by social environments. The author suggests that
      it was the appropriate social environment, medical improvement inherited from
      previous generations and Li Shizhen's contributions that led to the spread of
      Sanqi (Panax notoginseng) in the Ming Dynasty.

PMID- 15555247
TI  - [Medico-psychology in Huang di nei jing (Yellow Emperor's Inner Canon)].
AB  - Huang di nei jing (Yellow Emperor's Inner Canon) discusses spirit, mood, soul,
      idea, will, anxiety, worry, wisdom, morale and their relations with human life,
      physiology, and body-mind health. It also expounds the developmental rule of
      human body and mind, methods for keeping fit. These simple thinking of medico
      psychology reflects that Chinese doctors had advocated science since ancient
      times. The methodology of systematically and comprehensively discussing the
      relationship among nature, human body, visceral functions, and emotional
      activities reflects, again, the rather strong physiological dialectical thinking
      of ancient people.

PMID- 15555248
TI  - [Li Shizhen's cognition on human life].
AB  - Through the comparison between Taoists and physicians of ancient time in our
      country, we make inquiry into Li Shizhen's cognition on human life and consider
      that Li Shizhen explicitly put forward, prior to the contemporary physicians, the
      original creative ideas for the first time,on human being including "the brain is
      the residence of original spirit", "channel is the tunnel of inner image", "vital
      gate is located between the two kidneys", "vital gate is the substance, triple
      burner, the function". In addition to these ideas, Li Shizhen also raised an idea
      of "spleen is the mother of vital energy", which, even though it was not created
      for the first time, strengthened and developed the ideas of the predecessors.

PMID- 15555249
TI  - [William W. Cadbury and canton hospital].
AB  - William W. Cadbury M.D. was born in Philadelphia, USA and graduated from the
      Medical College of Pennsylvania University. It was nearly 40 years since he
      arrived in Canton (Guangzhou) in 1909 and left at retirement age. He taught
      western medicine in Canton Christian College and worked as a medical doctor in
      Canton Hospital, the oldest western medical hospital in the Orient. He was
      regarded as a famous foreign doctor and an excellent professor in internal
      medicine in the Republic of China. He wrote At the point of Lancet: 100 years of
      Canton Hospital 1835 - 1935, which recorded the achievement made by American
      missionary doctors, particularly the pioneers such as Peter Parker M.D. and John
      G. Kerr. M.D. So far the book is still an important reference for the studies on
      history of western medicine in China and the history of modern medical exchange
      between China and other countries.

PMID- 15555250
TI  - [A discussion on Zhang Cigong's materia medica].
AB  - Zhang Cigong's Materia Medica, being compiled by the author after learning and
      studying exogenous cold disease and herbology for several decades, printed in
      1949 with a capacity of 150,000 Chinese characters, is a book of practical and
      clinical significance, featuring adoration on the theory of cold pathogenic
      disease, preferential practical use, integration of Chinese and western medicine,
      pursuit of origin and evolution, discussion on the compatibility of drug
      application. It emphasizes the application of drugs utilized in Shang han lun
      (Treatise on Cold Pathogenic Disease) and advocating the ideas of absorbing
      extensively ancient and modern theories from various schools, especially
      consulting the pharmacology of Chinese and the west, embodying the author's
      advocacy of "developing the classical ideas and integrating new knowledge",
      "overcoming one's weak points by learning from others' strong points and making
      effort in inheriting and developing the science of traditional Chinese medicine".
      However, this book also bears some incorrect points which are not overall and
      comprehensive enough in the understanding of drugs, and thus, should be properly
      accepted and rejected.

PMID- 15555251
TI  - [Investigation on supplements from Tang Edition (TE) cited in Jia You ben cao
      (Materia medica of Jia You reign)].
AB  - Xin xiu ben cao (Newly Revised Materia Medica), also called Tang ben cao (Materia
      Medica of the Tang Dynasty) is the first state pharmacopoeia in the world, the
      original edition of which was lost yet cited by various books. After analyzing
      the TE in Jia You ben cao (Materia Medica of Jia You Reign) supplemantarily cited
      by Zhang Yuxi in the Song Dynasty, the author holds that Zhang himself didn't
      witness Xin xiu ben cao (Newly Revised Materia Medica) and the so-called TE ought
      to be derived from Shu ben cao (Materia Medica of Sichuan) because both share the
      same features. Inference can also be drawn that Xin xiu ben cao (Newly Revised
      Materia Medica) might have been lost at the time when Jia You ben cao (Materia
      Medica of Jia You Reign) was compiled in the 2nd year of Jia You Reign
      (A.D.1057). As the TE was not directly extracted from Xin xiu ben cao (Newly
      Revised Materia Medica), the trustworthiness of the texts allegedly cited from
      Xin xiu ben cao should be evaluated in many ways and it should be dealt with
      prudently while recompiling Xin xiu ben cao (Newly Revised Materia Medica).

PMID- 15555252
TI  - [Hardship of development of mini-invasive surgery: the hard history of
      sympathectomy].
AB  - The authors review the history of sympathectomy in the past more than fifty years
      and divide the whole course into four stages: thoracotomy, attempting toward mini
      invasion, conventional thoracoscopy and video-assisted thoracoscopy (VATS).
      Emphasis is laid on the difficult course of how this procedure has developed step
      by step from its original embarrassed 'large incision, small surgery' status to
      the modern mini-invasion surgery. The fact has proved that it is the modern
      natural science particularly the development and utilization of modern
      instruments that has notably promoted, and will continuously promote, the whole
      surgery toward mini-invasion.

PMID- 15555253
TI  - [Textual research on Lu You's poet on diseases during his trip to Nanchang].
AB  - By combining textual research on Bing Zhong Zuo (Poet Composed When Falling Ill)
      in Lu You's Jiannan shigao (Jiannan's Poetry Anthology), with other related
      historical materials, the geographical and climatic features of Nanchang area in
      the Southern Song Dynasty and epidemo1ogical characteristics of common diseases
      such as rheumatism, gastro-enteropathy and pulmonary diseases et al. thus
      happened can be clearly understood. It reflects the customs of the belief on
      witchery in medical treatment and the low medical level in Nanchang at that time.
      Meanwhile, it also reflects Lu You's optimistic attitude on his illness and his
      quiet, simple and open-minded idea of keeping fit.

PMID- 15555254
TI  - [Establishment and influence of Medical Professional Guarantee Committee (MPGC),
      Chinese Medical Association].
AB  - Established in 1933, MPGC was affiliated to Chinese Medical Association to
      safeguard doctor's legitimate rights and interests and quiet down medical
      disputes. The authors investigate its function and influence in the Republic of
      China, which offers a new angle of view in understanding the condition of western
      medicine in modern China.

PMID- 15555255
TI  - [Research on history of medicine in China in the last five years].

PMID- 15555256
TI  - [Review on the history of gynecology and obstetrics diseases of TCM in ancient
      times].

PMID- 15555257
TI  - [Effects of transforming growth factor beta1 on dendritic cells function].
AB  - OBJECTIVE: To investigate the effects of transforming growth factor beta1 (TGF
      beta1) on dendritic cells (DC). METHODS: Murine bone marrow cells were cultured
      with different cytokine combinations to develop immature DC (imDC, GM-CSF only)
      and TGFbeta-DC (GM-CSF + TGF-beta1), and their responses to lipopolysaccharide
      (LPS) stimulation were observed. The cell ultrastructure was observed by
      transmission electron microscopy and their phenotypes were assessed by flow
      cytometry (FCM). The allogeneic stimulating capacity of DC was assayed by mixed
      lymphocyte reaction (MLR) with BrdU incorporation. IL-12p70 protein was detected
      by ELISA and the expressions of Toll-like receptor 4 (TLR4) on DCs were analyzed
      with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
      RESULTS: Compared to imDC, the TGFbeta-DC had no significant alterations in
      ultrastructure after LPS stimulation. The expressions of CD80, CD86 were lower on
      TGFbeta-DC than on imDC [(4.14 +/- 0.95)% vs (13.90 +/- 7.22)%; (8.60 +/- 0.75)%
      vs (20.63 +/- 5.03)%, P < 0.05, both]. The TGFbeta-DC kept their immature
      morphology after LPS stimulation, but the expressions of I-Ab and CD80 were
      slightly increased. After 96 h MLR, TGFbeta-DC had weaker stimulating capacity
      than imDC did, especially when DC/T cells ratios were 1:4 and 1:1 (P < 0.05,
      both). TGFbeta-DC showed impaired IL-12p70 production and down-regulation of TLR4
      expression. CONCLUSIONS: TGF-beta1 can inhibit the expression of co-stimulatory
      molecules on DC. The TGFbeta-DC is resistant to maturation stimulus (LPS) and
      might be linked with TLR4 down-regulation.

PMID- 15555258
TI  - [Mismatched hematopoietic stem cell transplantation using GIAC protocol: report
      of 100 cases].
AB  - OBJECTIVE: To explore the clinical application of human leukocyte antigen (HLA)
      mismatched hematopoietic stem cell transplantation (HSCT) for malignant
      hematological diseases using a new GIAC protocol. METHODS: One hundred patients
      with malignant hematological disease received G-CSF mobilization, intensive
      immunosuppression, ATG and combination of bone marrow and peripheral blood stem
      cell transplantation at least 1 locus mis-matched hematopoietic stem cell
      transplant performed with GIAC protocol. The conditioning regimen was intensified
      and prolonged with combined use of CsA, MMF and ATG for GVHD prophylaxis.
      RESULTS: All patients achieved sustained, full donor-type engraftment. The
      cumulative incidence of grade II approximately IV aGVHD was 48.39%, and grade III
      approximately IV aGVHD was 12.90%. Thirty-eight patients had cGVHDs which were of
      extensive type in 11 patients. Twelve patients relapsed, 11 of them were high
      risk patients, and 3 returned to CR after donor lymphocyte infusion. Twenty-two
      patients died, owing to recurrent diseases in 6 and transplant-related
      complications in 16 cases. Seventy-two patients were alive and disease free, with
      1 year disease-free survival probabilities for standard and high risk patients of
      (83.52 +/- 7.41)% and (47.63 +/- 8.49)%, respectively. CONCLUSION: The GIAC
      protocol for at least 1 locus mismatched hematopoietic stem cell transplantation
      is relatively safe and efficient for patients with hematological malignancies.

PMID- 15555259
TI  - [T-bet gene expression in acute graft versus host disease].
AB  - OBJECTIVE: To study the role of T-bet [a T helper 1 (Th1) lymphocyte
      transcription factor] gene expression in predicting acute graft-versus-host
      disease (aGVHD) and evaluate the correlation between T-bet gene and aGVHD.
      METHODS: Twenty patients who underwent allogeneic stem cell transplantation
      (allo. HSCT) entered this study. The expression of T-bet gene was examined with
      reverse transcription (RT)-PCR in bone marrow samples collected from patients on
      the day before conditioning, and day 0, day 14, day 28, and day 42 after HSCT.
      RESULTS: The expression level of T-bet in patients developed aGVHD was increased
      compared with that before conditioning (P = 0.043). The incidence of aGVHD was
      91.7% in patients whose T-bet expression level was increased on day 14 after
      transplant while was 12.5% in those whose T-bet gene expression level was not
      increased on that day (P < 0.001). CONCLUSION: Patients with increased expression
      levels of T-bet after allo-HSCT may have an increased possibility to develop
      aGVHD. T-bet expression level may serve as an advisable guide to the clinician in
      predicting aGVHD and monitoring treatment.

PMID- 15555260
TI  - [Mobilization of peripheral blood stem cells with mitoxantrone and high-dose
      cytarabine chemotherapy and rhG-CSF in patients with hematopoietic malignancies].
AB  - OBJECTIVE: To evaluate the efficacy of mitoxantrone combined high dose of
      cytarabine and recombinant human granulocyte colony-stimulating factor (MAG)
      regimen for mobilizing autologous peripheral blood stem cells (APBSC) in patients
      with hematopoietic malignancies. METHODS: From December 1995 to April 2003, 14
      lymphoma and 29 acute leukemia patients were treated with high-dose cytarabine (2
      g/m2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m2, days 2 and 3),
      followed by 300 microgram recombinant human granulocyte colony-stimulating factor
      per day (rhG-CSF 300 microg/d) i.e, the MAG regimen as mobilization regimen of
      peripheral blood stem cells. rhG-CSF was given subcutaneously when the white
      blood cell (WBC) count below 1.0 x 10(9)/L following the MA chemotherapy, APBSC
      were harvested when WBC count increased using Baxter CS3000plus or Cobe Spectra.
      RESULTS: Mobilization was successful in 13 of 14 lymphoma patients with MNC (3.91
      +/- 2.70) x 10(8)/kg, CD34+ cells (17.79 +/- 12.90) x 10(6)/kg. Meanwhile,
      mobilization was successful in 24 of 29 acute leukemia patients with average of
      2.13 times for apheresis. The median MNC and CD34+ cells yielded were 3.62 x
      10(8)/kg and 7.37 x 10(6)/kg respectively, rhG-CSF was used for a median time of
      7 days. Excepting for grade I-II gastrointestinal toxicity in 8 and infection in
      14 cases, no major side effects were observed. There was no mobilization-related
      mortality. Minimal residual diseases became undetectable after mobilization in
      some patients. CONCLUSION: MAG is a safe and highly effective mobilization
      regimen in patients with lymphoma and acute leukemia.

PMID- 15555261
TI  - [The kinetics of hematopoietic cell chimerism in the early period after non
      myeloablative transplantation and its clinical implications].
AB  - OBJECTIVE: To analyze the kinetics of hematopoietic cell chimerism in the early
      period after non-myeloablative stem cell transplantation (NAST) and to
      investigate the correlation between molecular and hematologic assessment of
      engraftment or rejection. METHOD: Short tandem repeat-polymerase chain reaction
      (STR-PCR) analysis of chimerism status was carried out in 6 patients who received
      NAST from HLA-matched sibling donors. RESULTS: In 5/6 patients, the peripheral
      blood samples collected on the first day after allograft infusion displayed the
      presence of mixed chimerism. STR-PCR analysis revealed a gradual increase of the
      donor-specific allelic signal which became dominant over the recipient-specific
      allele by day +7. On day +14, hematologic chimerisms were completely donor
      origin. Their molecular engraftments (ME) were detected at a median time of 6
      days, preceding hematologic engraftment by a median of 5 days (P > 0.05). But the
      sixth patient showed more than 50% host residual cells on day +7 and had no signs
      of ME on day +14. CONCLUSION: It suggested that molecular monitoring of the early
      dynamics of chimerism after NAST could be useful in predicting engraftment, or
      rejection. If the engraftment was less than 50% on day +7 and failed to get ME on
      day +14, the graft rejection would occur.

PMID- 15555262
TI  - [Pulmonary disease caused by nontuberculous mycobacteria after allogeneic
      hematopoietic stem cell transplantation--a case report and literature review].
AB  - OBJECTIVE: To report a case with pulmonary disease caused by nontuberculous
      mycobacteria (NTM) after allogeneic hematopoietic stem cell transplantation (allo
      HSCT), with a literature review. METHODS: Case report and literature review.
      RESULTS: A patient with acute non-lymphocytic leukemia was treated by allo-HSCT.
      Her NTM lung disease developed after HSCT was successfully treated with a 3
      antimicrobials combination of clarithromycin, levofloxacin and capreomycin for 10
      months. CONCLUSION: NTM infections are infrequent in allo-HSCT recipients and
      have a good clinical prognosis if correctly treated.

PMID- 15555263
TI  - [Study of HLA polymorphism in the 6965 Han bone marrow registry donors].
AB  - OBJECTIVE: To analyze human leukocyte antigen (HLA) polymorphism and search for
      new alleles in Chinese Han population bone marrow registry donors. METHODS: DNA
      based HLA genotyping methods were used including PCR-SSP, BST and molecular
      cloning. RESULTS: A total of 6965 unrelated donors, 4707 from South China origin
      and 2258 from north, were typed for HLA-A, B, and DRB1 loci. Seventy-two
      specificities of HLA alleles were identified. The HLA-A25, A34, A74, B41, B42,
      B53, B73 and B81 that were rarely reported in previously Chinese population
      studies were identified in this study. Estimation of gene frequency indicated
      that the blank gene frequency was less than 0.2% for HLA-A, 0.25% for HLA-B and
      0.70% for HLA-DRB1 loci. Three novel alleles were identified and officially
      assigned by the World Health Organization (WHO) Nomenclature Committee as
      A*0253N, A*1114 and B*5610. CONCLUSION: Large-scale DNA-based HLA genotyping used
      in bone marrow registry donors is highly accurate and reliable for estimating
      gene frequency and searching for new alleles. The discrepancy of HLA gene
      distribution between South and North China Han population showed the necessity of
      setting the more regions in South and North China to screen the bone marrow
      registry donors for bone marrow transplant.

PMID- 15555264
TI  - [In vitro effect of interferon alpha on proliferation of human marrow
      fibroblast].
AB  - OBJECTIVE: To explore the effect of interferon alpha (IFN-alpha) on proliferation
      of human marrow fibroblasts. METHODS: Marrow fibroblasts were isolated from
      patients with iron deficiency anemia. Platelet derived growth factor-AB (PDGF
      AB), transforming growth factor-beta1 (TGF-beta1) or INF-alpha2b was added in the
      cell cultures each alone or in combinations. Cell proliferation and cell cycle of
      fibroblasts were detected by MTT and flow cytometry, respectively. RESULTS: PDGF
      ABqa (1 approximately 50 ng/ml) or TGF-beta1 (0.01 approximately 1 ng/ml) could
      stimulate the proliferation of the fibroblasts, while PDGF-AB was more effective
      (P < 0.01). IFN-alpha2b partially suppressed PDGF-AB induced proliferation of
      fibroblasts,the inhibition rate was 7.62%. IFN-alpha2b and TGF-beta1 combination
      suppressed synergistically not only the proliferation of the fibroblasts (P <
      0.01) but also the PDGF-AB induced-proliferation (P < 0.01) at S phase.
      CONCLUSION: IFN-alpha2b combined with TGF-beta1 could synergistically suppress
      the PDGF-AB induced proliferation of fibroblasts at S phase in vitro.

PMID- 15555265
TI  - [Karyotypic and IPSS grouping of primary myelodysplastic syndromes patients: a
      comparison between FAB- and WHO-classification].
AB  - OBJECTIVE: To compare the results of cytogenetic and IPSS grouping of primary
      myelodysplastic syndromes (pMDS) patients classified by FAB- or WHO
      classification. METHODS: Two hundred and thirty seven cases of pMDS who were
      previously classified according to FAB criteria were reclassified with WHO
      classification. A comparison was made between the results of the two
      classifications. RESULTS: For the detection rates of cytogenetic abnormality and
      its risks group, there was no difference among the FAB subgroups but the
      detection rate was different between the WHO refractory cytopenia with
      multilineage dysplasia (RCMD) and RA subgroups (74.4% and 42.5%, respectively) (P
      < 0.001). The percentage of good karyotype abnormalities in RA (65.0%) was higher
      than that in RCMD (24.4%) (P < 0.001), and the percentages of intermediate and
      poor karyotype abnormalities in RCMD (48.9% and 26.7%, respectively) were higher
      than that in RA (27.5% and 7.5%, respectively) (P < 0.05). There was a good
      correlation between the subgroups and IPSS risk groups for both the WHO
      classification and the FAB classification, but the WHO classification further
      reflected the differences between RCMD and RA and RAEB-I and RAEB-II subgroups.
      The percentage of low-risk group in RCMD (1.1%) was lower than that in RA (10.0%)
      (P < 0.05), and the percentage of high-risk group in RAEB-II (30.5%) was higher
      than that in RAEB-I(0) (P < 0.001). CONCLUSION: For the correlation between
      subgroups and cytogenetic abnormalities and IPSS risk groups, the WHO
      classification is better than the FAB-classification.

PMID- 15555266
TI  - [Growth and gene expression of leukemia cell after treated with methylation
      inhibitor 5-aza-2'-deoxycytidine].
AB  - OBJECTIVE: To investigate the mechanism of demethylation therapy of leukemia by 5
      aza-2'-deoxycytidine (5-aza-CdR). METHODS: By using MTT test, NBT reduction
      reaction and DNA agarose gel electrophoresis, changes in proliferation,
      differentiation and apoptosis were observed in K562, HL-60 and fresh leukemia
      cells after treated with 5-aza-CdR. The mRNA expressions of DNMTs, p15, p53 and
      bcl-2 were measured by RT-PCR. The status of p15(INK4B) gene methylation was
      examined by methylation-specific PCR (MSP-PCR). RESULTS: The growth inhibition of
      K562, HL-60 and fresh leukemia cells displayed a dose and time-dependent manner
      after treated by 5-aza-CdR. The differentiation-inducing ability on HL-60 cells
      was obvious at 0.5 micromol/L of 5-aza-CdR. The up-regulation of p15 mRNA and p53
      mRNA expression and down-regulation of bcl-2 mRNA expression were obvious as
      compared with the control, but the DNMTs expression was not significantly
      different from the control. The methylation status of p15 gene in fresh leukemia
      cells decreased gradually with increasing concentration of 5-aza-CdR. CONCLUSION:
      The proliferation of leukemia cells was obviously inhibited by 5-aza-CdR, its
      mechanism maybe related to the up-regulation of p15 and p53 genes and down
      regulation of bcl-2 gene. The decrease of p15 gene methylation was associated
      with the competitive inhibition of 5-aza-CdR.

PMID- 15555276
TI  - [Etiology and treatment of acquired pure red cell aplasia].

PMID- 15555277
TI  - [Clinical target volume in radiotherapy of non-small cell lung carcinoma].

PMID- 15555278
TI  - [Expressions and activities of Rho GTPases in hypoxia and its relationship with
      tumor angiogenesis].
AB  - OBJECTIVE: To study the expressions and activities of Rho GTPases in hypoxia and
      its relationship with tumor angiogenesis. METHODS: Three tumor cell lines were
      used in this study: gastric cancer cell lines AGS, SGC7901 and hepatocellular
      carcinoma cell line HepG2. Expression level of Rac1 mRNA was detected by semi
      quantitative RT-PCR. Activity of Rac1 was determined by pull-down assay and
      expression of HIF-1alpha, VEGF, p53 and PTEN protein was detected by Westernblot.
      RESULTS: The expression level of Rac1 mRNA was significantly increased in hypoxia
      compared to normoxia. Pull-down assay showed that hypoxia-induced activity of
      Rac1 was elevated in a time-dependent manner and climaxed at 3 hours. The
      expressions of HIF-1alpha and VEGF protein were up-regulated, while those of PTEN
      and p53 protein were down-regulated. CONCLUSION: These results indicate that
      hypoxia enhances Rac1 expression which might be involved in tumor angiogenesis by
      reacting with hypoxia-responsive genes.

PMID- 15555279
TI  - [Effect of overexpression of Smad7 gene on cell proliferation].
AB  - OBJECTIVE: To study the effect of overexpression of Smad7 gene on cell
      proliferation in human bronchial epithelial cell lines. METHODS: Human bronchial
      epithelial cell lines, BEP2D and BERP35T2 cells, were cotransfected with the
      mammalian expression vectors PCISmad7.neo and pMyc-SEAP, the latter was ac-myc
      cis-acting enhancer element fused with alkaline phosphatase (SEAP) reporter gene.
      Expression of c-myc, p15 and p21 mRNA was detected by RT-PCR before and after
      stable transfection of Smad7 into BEP2D and BERP35T2 cells in order to study the
      regulation of TGF-beta-mediated growth inhibition. RESULTS: After BEP2D and
      BERP35T2 cells transfected with Smad7, the transcriptional activity of c-myc was
      significantly increased. Smad7 overexpressing cells showed upregulation of c-myc
      expression and downregulation of p15 and p21 expression, which contributed to the
      loss of TGF-beta responses in these cells. CONCLUSION: Overexpression of Smad7
      may facilitate cell proliferation by antagonizing TGF-beta-mediated
      antiproliferative gene responses.

PMID- 15555280
TI  - [Effect of Ca2+ mobilization on release and activation of matrix
      metalloproteinases in hepatocellular carcinoma cells].
AB  - OBJECTIVE: To investigate the effect of Ca(2+) mobilization on release and
      activation of matrix metalloproteinases (MMPs) in human hepatocellular carcinoma
      cells. METHODS: Ca(2+) and chemicals which can induce or inhibit Ca(2+)
      mobilization were added into human SMMC-7721 hepatoma cells in vitro. SDS-PAGE
      protein electrophoresis and gelatin zymography analysis were carried out to
      detect the changes of release and activation of MMPs in the cell culture
      supernatant. RESULTS: Addition of CaCl(2) into culture system resulted in an
      enhanced secretion and activation of MMP-2 and MMP-9 in a dose-dependent manner.
      At a dose of 0.8 mmol/L CaCl(2), it maintained a stable high level of MMPs,
      especially of MMP-2 with (109.71 +/- 27.93)% elevation as compared to the cells
      without CaCl(2) addition (P < 0.001). SDS-PAGE analysis showed that most secreted
      proteins were MMPs (MMP-2 and MMP-9) when the cells cultured in media without
      serum. Thapsigargin (Tg, 4 micromol/L), an inducer of intracellular Ca(2+) stores
      depletion, significantly enhanced the release and activation of MMP-2 and MMP-9,
      compared to the control with (58.63 +/- 31.04)% elevation (P < 0.05), while the
      inducing effect of Tg on MMPs release and activation was significantly inhibited
      by S-nitro-N-acetylpenicillamine (SNAP, 200 micromol/L), an NO donor. CONCLUSION:
      Intracellular Ca(2+) regulation pathways may play an important role in the
      process of release and activation of MMPs.

PMID- 15555281
TI  - [Correlation between sensitivity to TRAIL and expression level of DR5 on surface
      of tumor cells].
AB  - OBJECTIVE: To investigate the correlation between sensitivity to tumor necrosis
      factor-related apoptosis inducing ligand (TRAIL) and expression level of death
      receptor 5 (DR5) on tumor cell surface. METHODS: Anti-DR5 mAb was used to detect
      expression level of DR5 on surface of tumor cells by flow cytometry. Sensitivity
      to apoptosis induced by TRAIL was determined by TRAIL apoptosis kit. The
      correlation between expression level of DR5 and sensitivity to TRAIL was
      analyzed. RESULTS: The expression of DR5 on surface of tumor cells was
      approximately 97.9% in U937 cells, 95.1% in Jurkat cells, 93.8% in SW480 cells,
      86.2% in HCT116 cells, 64.2% in HL-60 cells, 46.6% in HeLa cells and 13.1% in
      K562 cells, respectively. The apoptosis rate induced by TRAIL was 72.6% in U937
      cells, 85.2% in Jurkat cells, 78.6% in SW480 cells, 70.2% in HCT116 cells, 60.1%
      in HL-60 cells, 45.4% in HeLa cells and 12.3% in K562 cells, respectively. There
      was a significant positive correlation between the expression level of DR5 with
      TRAIL-inducing apoptosis (r = 0.997, P < 0.001). CONCLUSION: TRAIL-inducing
      apoptosis is related to the expression level of DR5 on surface of tumor cells.
      The results confirm the importance of DR5 expression for induction of apoptosis
      by TRAIL.

PMID- 15555282
TI  - [Ciglitazone inhibits growth of lung cancer cells A549 in vitro and in vivo: an
      experimental study].
AB  - OBJECTIVE: To study the inhibitory effects of ciglitazone, a synthetic ligand of
      peroxisome proliferator-activated receptors (PPAR), on human lung cancer growth
      in vitro and in vivo and its mechanisms. METHODS: Human lung cancer A549 cells
      cultured in vitro were treated with different concentrations of ciglitazone. The
      proliferative activity and cell cycle of A549 cells were determined by MTT assay
      and flow cytometry. Expression of PPARgamma protein was detected by Western blot.
      A549 cells (1 x 10(6) cells/nude mouse) were inoculated subcutaneously into nude
      mice, which were randomly divided into two groups, 10 in each: control group
      (group A) and ciglitazone treated group (group B). When the tumors grew to a size
      with diameter around 1 cm, ciglitazone 100 microl (100 micromol/L) was
      intratumorally injected every other day in group B mice. A total of 15 injections
      were given. Mice in group A were similarly treated with normal saline. One month
      later, tumors were excised and weighed. Expression of cyclin D1 and p21 protein
      were detected by immunohistochemistry and Western blot. RESULTS: Growth of A549
      cells was significantly inhibited in group B in a dose-dependent and time
      dependent fashion as compared with that in group A. Most of the ciglitazone
      treated cells arrested in G(1)/G(0) phase and the expression of PPARgamma protein
      was markedly up-regulated. The tumor weights in group A was (2.79 +/- 0.33) g and
      that in group B was (1.51 +/- 0.40) g, with an inhibition rate of 47.0%. The
      expression level of cyclin D1 in group A was significantly higher than that in
      group B, while the expression level of p21 protein in group A was significantly
      lower than that in group B. CONCLUSION: Ciglitazone can effectively inhibit the
      growth of human lung cancer A549 and induce its differentiation by cell cycle
      arrest via PPARgamma activation.

PMID- 15555283
TI  - [Synergistic inhibitory effect of STI571 in combination with arsenic trioxide on
      a multidrug-resistant leukemia cell line expressing bcr-abl].
AB  - OBJECTIVE: To study the synergistic effect of STI571, an inhibitor of tyrosine
      kinase in combination with arsenic trioxide (As(2)O(3)) on a multidrug-resistant
      leukemia cell line expressing bcr-abl. METHODS: The cytotoxic effect of STI571
      alone or in combination with different concentrations of As(2)O(3) on both bcr
      abl and mdr1 positive leukemia cell line K562-n/VCR was detected by MTT method.
      RESULTS: The cytotoxic effect of STI571 (1 micromol/L) combined with As(2)O(3) at
      concentrations 10(-5), 10(-6), 10(-7), 10(-8) mol/L (IC(50) 0.155 micromol/L) on
      K562-n/VCR cells was significantly higher than that of As(2)O(3) alone (IC(50)
      1.879 micromol/L). The synergistic interaction on K562-n/VCR cells increased the
      cytotoxic effect by 12.1-fold. CONCLUSION: Combination of STI571 with As(2)O(3)
      has a synergistic inhibiting effect on leukemia cells expressing bcr-abl and
      mdr1.

PMID- 15555284
TI  - [Expression and function of laminin receptor in laryngeal squamous cell
      carcinoma].
AB  - OBJECTIVE: To investigate the role of 67 000 laminin receptor (LN-R) in the
      processes of invasion and metastasis of laryngeal squamous cell carcinoma.
      METHODS: Expression of 67 000 LN-R mRNA in 20 cases with laryngeal squamous cell
      carcinomas and corresponding normal tissues was determined by RT-PCR, and the
      relationship between its expression level and patients' clinicopathological
      features was analyzed. Expression of 67 000 LN-R on the surface of AMC-HN-8
      laryngeal carcinoma cells was examined by flow cytometry. The effect of 67 000 LN
      R monoclonal antibody (MLuC5) on the adhesive and invasive abilities was observed
      by adhesion test and Boyden chamber invasiveness test in vitro. RESULTS: The
      expression level of 67 000 LN-R mRNA in human laryngeal squamous cell carcinoma
      was significantly higher than that in normal tissues (P < 0.05). The expression
      level of 67 000 LN-R mRNA in laryngeal squamous cell carcinomas with cervical
      lymph node metastases was higher than in those without cervical lymph node
      metastases (P < 0.05). There was a significant negative correlation between the
      expression level of 67 000 LN-R mRNA and the degree of tumor differentiation, the
      level being higher in poorly differentiated tumors (P < 0.05). Flow cytometry
      showed that (80.9 +/- 0.9)% of AMC-HN-8 cells expressed 67 000 LN-R. MLuC5
      inhibited the adhesion of AMC-HN-8 cells on LN, and after treated with MLuC5 for
      60 and 120 minutes, the adhesion inhibition rate was 57.1% and 63.2%,
      respectively. The invasive ability to artificial basement membrane was reduced by
      MLuC5. CONCLUSION: Laryngeal carcinoma overexpressing 67 000 LN-R has stronger
      invasiveness, and 67 000 LN-R monoclonal antibody may contribute to prevent
      metastasis of laryngeal carcinoma.

PMID- 15555285
TI  - [Detection of HPV 58 and cloning of its E7 gene in cervical cancer].
AB  - OBJECTIVE: To detect HPV 58, a common type of human papillomavirus (HPV), clone
      and express its E7 gene from biopsy specimens of cervical cancer. METHODS: HPV 58
      from 58 biopsy tissues of cervical cancer was detected by GP5+/GP6+ PCR followed
      by template-directed dye-terminator incorporation assay with fluorescence
      polarization detection (TDI-FP). HPV 58 E7 gene was amplified from one HPV 58
      positive sample, and then cloned into pGEM-T Easy vector. The recombinant
      plasmid, HPV58E7-pGEM-T was confirmed by sequencing. Subsequently, E7 gene was
      cloned into prokaryotic expression vector pRSET-A. The constructed pRSET-58E7
      plasmids were transfected into BL21(DE3) cells, and induced to express 58 E7
      protein by IPTG. RESULTS: Among the 58 biopsy tissues of cervical cancer, 10 were
      HPV 58-positive, accounting for 19.2% of 52 HPV-positive cases. HPV 58 E7 gene
      was amplified from one HPV 58-positive sample. The constructed plasmids were
      identified containing HPV58 E7 gene by restriction enzyme analysis and
      sequencing. SDS-PAGE analysis showed that HPV58 E7 His6 fusion protein of M(r) 16
      x 10(3) was expressed by pRSET-58E7 after induction by IPTG. The fusion protein
      accounted for 30% of total bacterial proteins. CONCLUSION: HPV 58 is not uncommon
      in Chinese women with cervical cancer in Shaanxi province. Constructed HPV58 E7
      recombinant plasmids can be effectively expressed in E.coli, which may provide a
      tool in diagnosis and vaccine design for HPV of HPV58-associated tumors.

PMID- 15555286
TI  - [Relationship between overexpression of the RIalpha subunit of the cAMP-dependent
      protein kinase and clinicopathological features of lung cancer].
AB  - OBJECTIVE: To explore the relationship between the overexpression of PKA RIalpha
      mRNA and cliniopathological parameters in lung cancer. METHODS: RT-PCR was used
      to detect the expression of PKA RIalpha mRNA in 54 cases with human lung cancer
      and matched normal tissues. RESULTS: (1) The expression of PKA RIalpha mRNA was
      significantly higher in cancer tissue (66.7%) than in normal tissues (20.4%) (P <
      0.01). (2) The expression was significantly correlated with TNM stage (P < 0.01),
      being increased with TNM stage. (3) The expression was significantly higher in
      patients with positive lymph nodes than in those with negative lymph nodes (P <
      0.01). (4) There were no significant associations of PKA RIalpha mRNA expression
      with histological type, differentiation grade or size of the tumor. CONCLUSION:
      This study indicates that the overexpression of PKA RIalpha mRNA may play an
      important role in the progression, metastasis and prognosis of lung cancer.

PMID- 15555287
TI  - [Expression of NFkappaB p65 and its target genes in gastric cancer and
      precancerous lesions].
AB  - OBJECTIVE: To study the expression of NFkappaB p65 and its target genes in
      intestinal metaplasia (IM), dysplasia (Dys), gastric cancer (GC) infected with
      Helicobacter pylori (Hp) and explore the mechanism of infection by cytotoxin
      associated antigen A expressing Hp (CagA(+)Hp) in the development of gastric
      cancer. METHODS: CagA antibody in blood sample of 289 patients was determined by
      ELISA. Hp was detected by rapid urease test and Warthin starry staining.
      Expression of NFkappaB p65 and its target genes in IM, Dys and GC was examined by
      immunohistochemistry. RESULTS: In IMI approximately II, IMIII, DysI, DysII
      approximately III and GC, the expression of NFkappaB p65 was significantly higher
      in patients with CagA(+)Hp infection than those without CagA Hp infection. In
      IMIII and DysII approximately III, the expression of NFkappaB p65, c-myc,
      CyclinD(1) and bcl-xl was significantly higher in patients with CagA Hp infection
      than those without CagA Hp infection. In gastric cancer infected with CagA(+)Hp,
      the expression of NFkappaB p65, c-myc, CyclinD(1) and bcl-xl was significantly
      higher in intestinal type than in diffuse type. CONCLUSION: There are different
      mechanisms in intestinal type and diffuse type in the development of gastric
      cancer. The occurrence of intestinal type gastric cancer is associated with
      CagA(+)Hp infection which by NFkappaB p65 upregulating the expression of c-myc,
      CyclinD(1),bcl-xl in patients with IMIII, DysII approximately III. It may be an
      effective method to prevent gastric cancer by inhibiting NFkappaB p65.

PMID- 15555288
TI  - [Intracranial metastasis of malignant tumors: clinical characteristics and MR
      imaging features].
AB  - OBJECTIVE: To study the clinical characteristics and MR imaging features of
      intracranial metastasis from malignant tumors. METHODS: 1271 patients who had
      history of primary tumor and suspected of cranial metastasis had MRI on Philips
      Gyroscan T5-NT MR scanner. The sequences included pre-contrast T(1)WI, FLAIR, and
      postcontrast transversal, sagittal, and coronal T(1)WI. All of the clinical data
      and MRI features of the patients were recorded and analyzed. RESULTS: Of 547
      patients with intracranial metastasis, 393 came from lung cancer (71.9%), 10% of
      547 patients were found to have the presenting symptoms of cranial metastasis.
      526 had parenchymal cerebral metastasis, and 21 only meningeal metastasis. Of
      these 526 patients found to have brain metastasis, 164 had single metastasis
      (31.2%), and 362 multiple (68.8%). Most of the cerebral metastatic lesions showed
      uniform or ring enhancement after intravenous injection of contrast medium, dura
      arachnoid metastasis showed continuous and thick-curve enhancement at the
      cerebral convex, but not extending to the sulcus, while pia-dura metastasis
      displayed as thin and linear or nodular enhancement extending to the adjacent
      sulci. CONCLUSION: The most common primary lesion with metastasis to the brain
      were lung cancers, followed by breast and gastrointestinal cancers. By using
      gadolinium-DTPA enhanced MR imaging, many single and small cerebral metastasis
      could be found earlier.

PMID- 15555289
TI  - [The value of Roferon-A combined with hepatic artery chemoembolization and portal
      vein chemotherapy after radical resection in hepatocellular carcinoma for
      preventing recurrence].
AB  - OBJECTIVE: To explore the change of T cell subsets in patients suffered from
      hepatocellular carcinoma (HCC) before and after hepatectomy, and study the value
      of Roferon-A (interferon alpha-2a) combined with hepatic artery chemoembolization
      (HACE) and portal vein chemotherapy (PVC) after radical resection of HCC for
      preventing recurrence. METHODS: On 75 HCC patients, PVC and HACE were
      respectively given at 2 weeks and 4 weeks after radical tumor resection. In 2nd
      week after surgery, 33 cases of them accepted Roferon-A treatment for 1 week.
      Seventy-two patients were followed up over 3 years. Effect of Roferon-A combined
      with HACE and PVC on postoperative recurrence rate was compared with that of HACE
      and PVC. Changes of T cell subsets in peripheral blood were examined with labeled
      monoclonal antibodies before and after hepatectomy or using interferon. Forty
      cholecystolithiasis patients received cholecystectomy were used as the controls.
      RESULTS: CD(3)(+) and CD(4)(+) cells in peripheral blood were reduced in patients
      with HCC. After hepatectomy, they declined further with decrease in
      CD(4)(+)/CD(8)(+) ratio. The results returned to pre-operative level at the end
      of 4th week after surgery. The CD(3)(+), CD(4)(+) cells and the CD(4)(+)/CD(8)(+)
      ratio increased remarkably following the use of Roferon-A. The 1-, 2- and 3-year
      recurrence rates of patients treated with HACE, PVC and Roferon-A in combination
      were 0%, 6.2% and 15.6%, respectively, while those treated with HACE and PVC were
      5.0%, 12.5% and 27.5%, respectively. CONCLUSION: Patients with HCC suffer from
      marked immuno-suppression which became ever more severe after hepatectomy,
      combined use of HACE, PVC and Roferon-A is superior to only HACE and PVC by
      decreasing the recurrence rate.

PMID- 15555290
TI  - [Taxol based chemotherapy in the treatment of advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of taxol-based chemotherapy in
      the treatment of advanced gastric cancer (AGC). METHODS: Twenty-nine patients
      with AGC treated with taxol-based protocols: taxol plus 5-fluouracil 17 patients,
      taxol plus cisplatin 10 patients, taxol plus epirubicin 2 patients. RESULTS:
      Twenty-six patients were evaluated for clinical response. There was no complete
      response, PR 10 (34.5%), SD 12 (41.4%), PD 4 (13.8%). The total response rate was
      34.5%. The clinical beneficial response rate was 72.4% (21/29). Median time to
      progression (mTTP) was 5.8 months and median overall survival time was 9.3
      months. The main side effects were: suppression of bone marrow in 26 patients
      (89.7%), alopecia in 25 (86.2%), myodynia and arthrodynia in 23 (79.3%). There
      was no death during the treatment. CONCLUSION: Taxol-based chemotherapy is an
      effective and well tolerated regimen in the treatment of AUC, which can relieve
      suffering and improve quality of life of the patients. It can be used as the
      second-line therapy for relapsed advanced gastric cancer.

PMID- 15555291
TI  - [Capecitabine combined with TACE for advanced liver cancer].
AB  - OBJECTIVE: To evaluate the clinical efficacy of capecitabine combined with
      transcatheter arterial chemoembolization (TACE) for advanced liver cancer.
      METHODS: Forty-nine patients with liver cancer were retrospectively divided into
      two groups: Treatment group, on the basis of TACE, 23 patients received oral
      capecitabine at 2500 mg/m(2), twice-daily for 14 days followed by 7-day rest
      period and repeated in every three week intervals for more than two cycles.
      Control group, 26 patients received TACE only at 2-month intervals for at least
      two cycles. RESULTS: In capecitabine and TACE group: there were 1 CR, 14 PR, 5 SD
      and 3 PD; the overall response rate was 65.2%; the AFP and tumor reduction rates
      were 68.8% and 73.9%; the median survival time was 11.9 months. In the TACE only
      group: there were 0 CR, 7 PR, 12 SD and 7 PD; the overall response rate was
      26.9%; the AFP and tumor reduction rates were 31.6 % and 30.8%; the median
      survival time was 8.3 months. The most common side-effects of capecitabine were
      hand-foot syndrome and diarrhea. CONCLUSION: Capecitabine combined with TACE is
      safe and effective for advanced liver cancer.

PMID- 15555292
TI  - [Focal nodular hyperplasia of the liver: a clinical study of 48 patients].
AB  - OBJECTIVE: To study the diagnosis and proper treatment of focal nodular
      hyperplasia (FNH) of the liver. METHODS: Forty-eight consecutive patients with
      FNH treated from 1998 to 2002 were analyzed. Clinical, pathologic, and
      preoperative imaging findings of FNH all proved surgically and pathologically
      were retrospectively reviewed. RESULTS: Most of the patients were asymptomatic
      and serum test was normal. Helical multiphasic liver CT and MR imaging
      demonstrated characteristic features in 25 patients. Histologically,
      characteristic scar-like tissues were found in 29 cases. The overall complication
      rate was 2.1% and there was no death. No recurrence was observed after follow-up
      of 4 years after operation. CONCLUSION: There is little evidence for an increased
      risk for FNH in people using modern oral contraceptives, while characteristic
      imaging features exist in helical multiphasic liver CT and MR imaging. Operation
      is the optimal treatment for FNH, but for proved FNH less than 5 cm and
      asymptomatic patients, close periodic followed up should be done.

PMID- 15555300
TI  - [Basic occupational health service for all the workforce].

PMID- 15555301
TI  - [Potential effect of tumor necrosis factor-alpha and tumor necrosis factor
      receptor II gene polymorphisms on the pathogenesis of silicosis].
AB  - OBJECTIVE: To approach the role of tumor necrosis factor-alpha (TNF-alpha) and
      tumor necrosis factor receptor II (TNFR II) gene polymorphisms in genetic
      susceptibility to silicosis and their interaction with silica-dust exposure.
      METHODS: Two hundred and fifty-nine cases of silicosis and three hundred and
      forty-one silica-dust exposure workers (control) were selected, and the cases of
      silicosis were divided into three subgroups based on the various stages of I, II
      and III. Exposure history, pneumoconiosis history and past history of each
      subject were obtained by questionnaire. 3 ml peripheral venous blood was drawn
      from each subject. Using polymerase chain reaction-restriction fragment length
      polymorphisms (PCR-RFLP) techniques, TNF-alpha and TNFRII gene polymorphisms were
      analyzed. RESULTS: In both group matching and 1:1 paired matching, there was no
      significant difference between cases of silicosis and workers in control in
      distribution frequencies of G/A + A/A (TNF-alpha-308) and T/G + G/G (TNFRII 196)
      genotypes. The risk of silicosis in those with G/A + A/A genotype was 6.74-fold
      higher than G/G genotype (OR = 6.74, 95% CI: 1.01 approximately 44.99) in
      subjects whose exposure time was less than 15 years. CONCLUSION: TNF-alpha and
      TNFR II gene polymorphisms did not play an important role in susceptibility to
      silicosis of Han race. There was interaction between polymorphism of TNF-alpha
      gene promoter and exposure time in the occurrence of silicosis. The risk of
      silicosis in those with G/A + A/A genotype was significantly higher than G/G
      genotype in low accumulative exposure.

PMID- 15555302
TI  - [Occupational exposure profiles of polycyclic aromatic hydrocarbons in coke oven
      workers].
AB  - OBJECTIVE: To study the characteristics of occupational exposure of polycyclic
      aromatic hydrocarbons (PAHs) in coke oven workers. METHODS: Samples were
      collected individually and PAHs concentration in the ambient air were assayed by
      high performance liquid chromatography (HPLC) and toxic equivalency factors
      (TEFs) were introduced to assess the carcinogenic potency. RESULTS: The levels of
      PAHs occupational exposure in oven workers at topside was higher than at side
      oven and bottom oven (P < 0.05). Non-carcinogenic PAHs were more than 70% of
      total PAHs and benzo[a]pyrene accounted for 65.5% approximately 72.4% of total
      benzo[a]pyrene equivalents. Total occupational exposure level of PAHs in coke
      oven workers was positively related to the content of benzo[a]pyrene and pyrene,
      respectively (r(2) = 0.84, r(2) = 0.94, P < 0.05). CONCLUSION: Coke oven workers
      were exposed to a high level of PAHs which possessed some extent of carcinogenic
      potency, and benzo[a]pyrene is the chief carcinogenic substance.

PMID- 15555303
TI  - [The role of cycline dependent kinase 4 in the malignant transformation induced
      by silica].
AB  - OBJECTIVE: To study the role of cycline dependent kinase 4 (CDK4) in the
      malignant transformation of human fetal lung diploid fibroblast cell (2BS)
      induced by silica. METHODS: Recombination vectors with antisense pXJ41-CDK4 were
      constructed, and then were transfected into the malignant transformed cells
      induced by silica. In situ hybridization and immunohistochemistry were used to
      analyze the expression of CDK4. Cell growth curve, doubling time, cell cycle
      distribution and the growth capacities on soft agar were analyzed before and
      after antisense CDK4 RNA was transferred into malignant transformed cells induced
      by silica. RESULTS: During the malignant transformation of 2BS cells induced by
      silica, CDK4 gene was overexpressed. Antisense pXJ41-CDK4 transduction suppressed
      CDK4 gene expression in the antisense pXJ41-CDK4 transfected cells. Antisense
      CDK4 RNA led to cell cycle arrest, resulting in lengthened G1 phase (the
      percentages of cells in the G1 phase increased from 45.1% to 58.0%), and
      eventually attenuated the proliferation of malignant transformed cells induced by
      silica. At the 8th day, the suppression rates decreased by 77.43%. The doubling
      time prolonged from 21.0 h to 42.7 h. The growth capacities on soft agar of cells
      transfected by antisense pXJ41-CDK4 were decreased. CONCLUSION: CDK4 might play
      an important role in maintaining the transformed phenotype of the cancer cells.

PMID- 15555304
TI  - [Clinical analysis of 15 cases of acute tetramine poisoning].

PMID- 15555305
TI  - [A study on the variation in classifying chest radiographs for pneumoconiosis].
AB  - OBJECTIVE: To study the interobserver variation and its sources in classifying
      chest radiographs of pneumoconiosis for improving diagnostic quality. METHODS: A
      set of 240 high-voltage chest radiographs including different stages of
      pneumoconiosis was developed and 5 sets of copies were made in the same
      condition. It was read by 7 experienced readers independently in eligible
      situation. Results of reading were recorded in unified reading sheets. The
      profusion of small opacities and the stage of pneumoconiosis were recorded as
      corresponding numerical value for analysis. RESULTS: The coefficients of
      variation of 7 readers in total profusion of small opacities, average profusion
      of small opacities and stage of pneumoconiosis were 15.17%, 15.91%, 12.06%,
      respectively. The judgement of the presence or absence of small opacities, large
      opacities and coalescence of small opacities were closer, and the rates of
      consistency were 91.09%, 91.93% and 76.41% respectively. Technical quality of the
      radiographs in this study could not make a considerable impact on the reading
      results. If the shape of small opacities were recorded consistently by most
      readers as small rounded opacities or small irregular opacities, the judgement of
      total profusion of small opacities and stage of pneumoconiosis were more
      consistent; if the shape of small opacities were recorded inconsistently, the
      difference of judgement was higher. CONCLUSION: Interobserver variation exists
      actually among different readers and the main sources of the variation come from
      uncertain judgement of the shape of small opacities.

PMID- 15555306
TI  - [Preliminary study on the relationship between chronic sinusitis histomorphology
      and aerosol].
AB  - OBJECTIVE: To observe the relationship between histomorphological changes in
      mucosa of chronic sinusitis (CS) and aerosol particles. METHODS: The ethmoidal
      sinus mucus specimens of 60 patients with CS type I, II and III, and 16 cases of
      normal controls were collected. Meanwhile the pulmonary specimens in autopsy of 5
      adult and 5 fetus cases were also collected. The specimens were stained by HE
      staining and Warthin-Starry (W-S) special aerosol particles staining method
      respectively, the ethmoidal sinus mucosa basement membrane were displayed by Van
      Gieson's (VG) special staining method, and its thickness was measured. RESULTS:
      By the W-S staining, some black aerosol particles were found depositing on the
      epithelial cells layer of damaged mucosa and in the plasm of the epithelial
      cells. The degree of deposition was gradually increased in type I, II and III of
      CS. The number of cases of slight, medium and heavy depositing in type I were
      11/20, 7/20, 2/20, in type II 5/20, 9/20, 6/20, and in type III 3/20, 6/20, 11/20
      respectively; the more particles deposited, the more thickening the basement
      membrane. The thickness of the basement membrane in type I, II and III of CS were
      (12.15 +/- 4.73), (16.67 +/- 2.22), (23.75 +/- 3.48) microm respectively. There
      were significant differences among type I, II and III (P < 0.01). The black
      particles in the mucosa epithelium tissues of normal control group and non
      damaged mucosa epithelium and desquamation area were seldom seen. On the other
      hand, the aerosol particles were not seen in the pulmonary specimens of the fetal
      autopsy. CONCLUSION: In damaged mucosa epithelial cells of the CS, there are
      aerosol particles existing which may relate with the morphological changes of CS.

PMID- 15555307
TI  - [Characteristics of the occurrence of silicosis in the workers exposed to uranium
      dust].
AB  - OBJECTIVE: To understand the laws and characteristics of silicosis incidence of
      the workers exposed to the uranium dust from 1956 to 2002. METHODS: The length of
      employment, age of occurrence of silicosis, and its duration and death age were
      compared between the uranium miners and uranium geological prospecting teams, and
      also between the miners exposed to uranium dust and those exposed to mixed
      uranium dust by single factor analysis method. RESULTS: With time going on, the
      length of employment, age of occurrence of disease and its duration and death age
      were prolonged respectively in the workers exposed to uranium dust. The length of
      employment and age of occurrence of disease in uranium geological prospecting
      teams [(10.15 +/- 5.95) and (40.60 +/- 9.86) years respectively] were shorter
      than those in uranium miners [(14.23 +/- 8.12) and (41.38 +/- 10.98) years], but
      the duration (P(50)) and death age were longer [(14.29 years vs 12.52 years),
      (53.69 +/- 10.04) years vs (51.45 +/- 10.85) years respectively]. The length of
      employment and age of occurrence of disease in those exposed to uranium dust only
      [(11.78 +/- 8.06) and (38.04 +/- 9.89) years] were shorter than those exposed to
      mixed uranium dust [(12.74 +/- 6.29) years, (41.40 +/- 10.67) years], but the
      duration (P(50)) and death age were longer than the mixed uranium dust ones
      [(14.59 years vs 13.20 years), (53.93 +/- 10.60) years vs (51.82 +/- 10.20)
      years]. CONCLUSION: The difference in the occurrence of silicosis in the workers
      exposed to uranium dust may be attributed to the physical and chemical character
      of the uranium dust and the different working circumstance.

PMID- 15555308
TI  - [Thirty-two cases of pneumoconiosis complicated by pulmonary fungus infection].

PMID- 15555309
TI  - [Expression of Smads in lung tissue of quartz-induced pulmonary fibrosis in
      mice].
AB  - OBJECTIVE: To observe Smads protein expression in lung tissue of quartz exposed
      mice and to explore its association with pulmonary fibrosis in silicosis.
      METHODS: The experimental mice were divided into control and quartz groups. 0.2
      g/kg weight of quartz was injected intratracheally in quartz group. Samples were
      collected at the 1st, 3rd, 5th, 7th, 14th and 28th day after injection.
      Immunohistochemical methods with quantitative image analysis were used to assay
      the protein expression of transforming growth factor beta(1) (TGF-beta(1)), Smad
      2/3, Smad 4, and Smad 7 protein levels. Protein expression level is presented by
      positive unit (PU). RESULTS: Smad 2/3 protein expression increased from day 3,
      reaching its peak level in day 14 [(42.2 +/- 2.4) PU], and decreased gradually.
      The elevation of Smad 4 protein level began from day 5, and the highest degree
      came into day 14 [(40.0 +/- 1.8) PU], decreased thereafter. The expression of
      Smad 7 presented a decreasing tendency at the beginning and reaching the lowest
      level in day 14 [(33.5 +/- 3.3) PU]. It seemed to elevate in day 28, but was
      still lower than the controls. There were positive correlation between Smad 2/3,
      Smad 4 and TGF-beta(1) (r = 0.91, r = 0.71, respectively, P < 0.05) and also
      between Smad 2/3 and hydroxyproline contents of lung tissue (r = 0.85, P < 0.05)
      except Smad 7. CONCLUSION: Smad protein may have certain association with
      pulmonary fibrosis in silicosis.

PMID- 15555310
TI  - [Effect of gamma-interferon on protein expressions of interleukin-4 and
      transforming growth factor-beta1 in experimental silicotic rats].
AB  - OBJECTIVE: To study the effect of gamma-interferon on the protein expressions of
      interleukin-4 (IL-4) and transforming growth factor-beta(1)(TGF-beta1) on
      silicotic rats. METHODS: Wistar rats were exposed to lower dose (20 mg) of quartz
      by intratracheal injection. Next day, the experimental rats were treated with
      gamma-interferon (1 x 10(5) IU) daily. Rats were killed in 1 month and 2 month to
      observe the changes of pathology of lung tissue by use of HE and VG staining, and
      the expressions of IL-4 and TGF-beta1 by use of immunohistochemical technique and
      quantitative analysis of protein expressions by image analysis system. RESULTS:
      (1) The fibrotic degree in silicotic lesions of rat lung was 1/2 approximately 1
      grade less in IFN-gamma treated groups than in quartz controls. (2) Quantitative
      image analysis showed that the integrated optical density (IOD) of IL-4 positive
      cell in quartz controls in 1 month was (3.33 +/- 1.27) x 10(4) and decreased to
      (1.99 +/- 0.80) x 10(4) in 2 month, and that of TGF-beta1 positive cell increased
      from (3.67 +/- 0.63) x 10(4) to (4.90 +/- 1.11) x 10(4); The IOD of IL-4 positive
      cell in IFN-gamma treated groups was decreased from (2.19 +/- 0.90) x 10(4) to
      (0.61 +/- 0.22) x 10(4)(P < 0.05), and that of TGF-beta1 positive cell increased
      from (1.37 +/- 0.31) x 10(4) to (1.76 +/- 0.72) x 10(4) (P < 0.05). At these two
      time points, the IODof IL-4 and TGF-beta1 positive cell in IFN-gamma treated
      groups were lower than those in quartz controls (P < 0.05 or P < 0.01).
      CONCLUSION: gamma-interferon may inhibit the expressions of IL-4 and TGF-beta1 in
      silicotic rats.

PMID- 15555311
TI  - [Relationship between bleomycin-induced pulmonary fibrosis and vascular
      endothelial cell injury].
AB  - OBJECTIVE: To explore the relationship between the injury of vascular endothelial
      cells and formation of lung fibrosis by bleomycin (BLM) in rats. METHODS: The
      rats of experimental groups were treated with bleomycin intratracheally to induce
      pulmonary fibrosis. The expression of vascular endothelial growth factor (VEGF)
      in pulmonary tissues were analyzed qualitatively and quantitatively by
      immunohistochemistry and image analysis system. RESULTS: (1) HISTOLOGY: Edema in
      rat alveoli and alveolar septum, inflammatory cells exudation, degeneration and
      necrosis of type I and type II alveolar epithelial cells (AETI and AETII),
      ruptured alveolar basement membrane, as well as swollen vascular endothelial
      cells and karyopyknosis were observed in 3 d and 7 d after treatment with BLM.
      AETII proliferation, with more fibroblasts in alveolar septum, and new capillary
      vessel formation in 7, 14 d, as well as thickened alveolar septum, damaged
      alveolar structure, and obvious pulmonary tissue fibrosis in 28 d after treatment
      with BLM were observed. (2) Immunohistochemistry: in normal control, VEGF
      expressed weakly in pulmonary tissue distributing mainly in AETII, bronchial
      epithelial cells, alveolar macrophages and leydig's cells. While in bleomycin
      treated groups, the expression of VEGF increased markedly. The expression in
      AETII, and pulmonary macrophage were significantly higher than that in control in
      3 d to 28 d (P < 0.05, P < 0.01). The rat leydig's cells also had higher
      expression of VEGF in 7, 14, 28 d (P < 0.05, P < 0.01). CONCLUSION: The high
      expression of VEGF is related to vascular endothelial cells injury which may be
      one of important factors in the formation of bleomycin-induced pulmonary
      fibrosis.

PMID- 15555312
TI  - [Effect of human silicotic alveolar macrophages on the expression of matrix
      metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 in human lung
      fibroblasts].
AB  - OBJECTIVE: To study the effect of the cultured supernatant of human silicotic
      alveolar macrophages (AM) on the expression of matrix metalloproteinase-1 (MMP-1)
      and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human lung fibroblasts
      (FB). METHODS: Human alveolar macrophages were collected from a silicotic
      patients by bronchoalveolar lavage and exposed to SiO(2), then the cultured
      supernatant were incubated with human fetal lung fibroblasts for 6, 12, 18, 24,
      36, 48 h. The immunocytochemical method was used to detect the level of
      expression of MMP-1 and TIMP-1 in lung fibroblasts. RESULTS: The expression of
      MMP-1 in FB in 24 h incubation was lower in cultured supernatant of silicotic AM
      unexposed to SiO(2) than in blank control [integrated OD (IOD)]: 0.103 +/- 0.014
      vs 0.133 +/- 0.023), while the expression of TIMP-1 was higher (IOD: 0.108 +/-
      0.012 vs 0.065 +/- 0.006). The expression of MMP-1 in FB in cultured supernatant
      of AM exposed to SiO(2) for 24 h was further decreased (IOD: 0.062 +/- 0.008 vs
      0.133 +/- 0.023), while that of TIMP-1 was further increased (IOD: 0.143 +/-
      0.015 vs 0.065 +/- 0.006). CONCLUSION: SiO(2) may affect the expression of MMP-1
      and TIMP-1 system through AM mediation and participate in the formation of lung
      fibrosis.

PMID- 15555313
TI  - [The dynamic changes of collagen fiber in quartz-induced pulmonary fibrosis in
      mice with picrosirius red plus polarized microscopy in vivo].
AB  - OBJECTIVE: To investigate the use value of picrosirius red staining plus
      polarized microscopy to observe the dynamic changes of collagen fiber in lung
      fibrosis in silicotic mice model. METHODS: The experimental mice were divided
      into control and quartz groups. 0.2 g/kg weight of quartz was injected
      intratracheally in quartz group. Lung tissues were collected at the 1st, 3rd,
      5th, 7th, 14th and 28th day after injection respectively. Lung tissue slides were
      stained with picrosirius red. With the aid of polarized microscope, image
      analysis software, the distribution and change of type I and type III collagen
      could be qualitatively and quantitatively analyzed. Lung tissue hydroxyproline
      was determined by chloramines T method. RESULTS: In early stage the predominant
      increment was type III collagen, but in late stage type I was predominant. The
      contents of both type collagen tended to increase as postexposure time prolonged.
      The time course of the ratio of type I to type III showed increasing trend, and
      there was a statistical significance on day 28 (1.49 +/- 0.39 vs 0.59 +/- 0.24, P
      < 0.05). The total area of collagen was positively correlated with hydroxyproline
      concentration of lung tissue (r(2) = 0.928 5, P < 0.01). CONCLUSION: Picrosirius
      red staining combined with polarized microscopy and digital image processing is a
      useful method to elucidate collagen accumulation, distribution and subtype ratio
      in silicosis.

PMID- 15555314
TI  - [A survey of emergency treatment of pesticides poisoning in comprehensive
      hospitals].
AB  - OBJECTIVE: To seek the characteristics of pesticide poisoning in emergency
      departments. METHODS: Twenty-five hospitals were selected. Among them, they were
      14 province or city level and 11 county level. The object of study was the
      patients with pesticide poisoning who were first visit to a doctor (including
      transfer to the above emergency departments of hospitals) from July 1, 2001 to
      June 30, 2002. RESULTS: There were 2 261 cases of pesticide poisoning that ranked
      third place of total acute poisoning cases at the same period. Gender ratio was 1
      male to 1.47 female. Among 1 618 patients who first visited to emergency
      departments (excluding transfer), 43.9% were by emergency ambulance. 68.3% of
      total cases were caused by intentional exposure to pesticides, of which female
      accounted for 75.8%. Young people aged 15 to approximately 34 years accounted for
      47.5% of all cases. Children (0 to approximately 14 years) also had relatively
      high pesticide poisoning rates, particularly an accident pesticide poisoning for
      1- to approximately 4-year-old children accounted for 65.9% of total acute
      poisoning in the age group. 98.2% of all cases needed urgent medical treatment,
      and 52.4% were hospitalized. The leading occupation of patients was farmers
      followed by housekeepers, students and preschoolers. Insecticides poisoning
      accounted for 60.1% of all pesticides. The fatality rate in emergency department
      was 3.9%. 60.8% case was collected from county hospital. Pesticide poisoning rank
      first place of total acute poisoning cases in county hospital. CONCLUSION: A
      safety education of Knowledge Attitude Practice (KAP) is an effective measure for
      preventing pesticide poisoning.

PMID- 15555315
TI  - [Effects of pyrethroids on dopamine and its metabolites in nigrostriatum of male
      rats].
AB  - OBJECTIVE: To investigate the effects of pyrethroids on nigrostriatal
      dopaminergic pathways in male rats and its mechanism. METHODS: Different doses of
      permethrin (PM, 200, 400 mg/kg) and deltamethrin (DM, 6.25, 12.50 mg/kg) in corn
      oil were administered to rats by gavage once daily for ten days, then the
      contents of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) in the substantial nigra and striatum were
      analyzed by HPLC-fluorescence detection. RESULTS: The contents of DA in striatum
      in four administered groups were decreased to a certain extent. DA in 6.25 mg/kg
      DM group [(6.14 +/- 0.57) microg/g wet weight] was lower than that in control
      group [(9.46 +/- 1.95) microg/g wet weight], P < 0.05. The turnover rate of DA in
      200, 400 mg/kg PM and 6.25, 12.5 mg/kg DM groups increased by 133.33%, 166.67%,
      166.67%, 266.67% respectively (P < 0.05 or P < 0.01), however there was no
      significant difference in DA and DOPAC in substantial nigra between control and
      administered groups. CONCLUSION: DM may inhibit tyrosine hydroxylase and decrease
      the level of DA in striatum, and both pyrethroid pesticides may increase the
      metabolism of dopamine in striatum.

PMID- 15555316
TI  - [Effects of deltamethrin on the apoptosis and the expression of caspase-3 in rat
      neural cells].
AB  - OBJECTIVE: To study the effect of deltamethrin on the apoptotic rate and the
      expression of caspase-3 in rat neural cells. METHODS: Male Wistar rats were
      randomly divided into 5 groups: control, 5 h, 24 h, 48 h and 5 d exposed groups.
      Apoptotic rate and the expression of caspase-3 were measured by FACS420 Flow
      Cytometer; Ac-DEVD-pNa was used as a substrate to detect the activity of caspase
      3. RESULTS: Apoptotic rates in 24 h, 48 h and 5 d exposed groups in hippocampus
      and cerebral cortex [hippocampus: (8.45 +/- 1.02)%, (9.44 +/- 1.14)%, (7.58 +/-
      0.75)%; cerebral cortex: (7.90 +/- 0.49)%, (8.01 +/- 0.87)%, (7.97 +/- 0.41)%
      respectively] were higher than those in the control [hippocampus: (2.97 +/-
      0.36)%; cerebral cortex: (3.50 +/- 0.48)%] (P < 0.01); the activity of caspase-3
      in 5 h, 24 h and 48 h exposed groups (A(405) nm in hippocampus: 0.389 +/- 0.038,
      0.472 +/- 0.041, 0.295 +/- 0.049; A(405) nm in cerebral cortex: 0.321 +/- 0.068,
      0.429 +/- 0.077, 0.344 +/- 0.047) and 5 d group of hippocampus (0.246 +/- 0.065)
      were all higher than those of the control (hippocampus: 0.184 +/- 0.054; cerebral
      cortex: 0.198 +/- 0.049) (P < 0.05, P < 0.01); the expression of caspase-3 in 5
      h, 24 h and 48 h exposed groups increased apparently while 5 d group did not.
      CONCLUSION: Exposure to high dose of deltamethrin would affect the apoptosis, the
      activity and expression of caspase-3 in rat neural cells. The increase in caspase
      3 activity and expression occurred before the rising of neuronal apoptotic rate
      may be the upstream event of apoptosis.

PMID- 15555317
TI  - [Expression of the heat-shock protein 70 family polymorphism in A549 cell line
      exposed to benzo(a)pyrene].
AB  - OBJECTIVE: To study the pattern of polymorphism expression of heat-shock protein
      70 (HSP70) family in A549 cell line treated with different concentrations of
      benzo(a)pyrene (BaP) and its probable biological effect. METHOD: Two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) was used for the HSP70 expression
      analysis. RESULTS: 2D-PAGE showed that when A549 cells were exposed to different
      concentrations of BaP (0.1, 1.0, 5.0, 10.0 micromol/L) for 24, 48 h respectively,
      the HSP72 in A549 gradually declined as BaP concentrations increased [the
      integral OD (IOD)] for 24 h were: 150.36 +/- 26.03, 98.57 +/- 13.34, 64.92 +/-
      15.03, 34.65 +/- 19.10, 32.92 +/- 18.71 respectively, for 48 h: 126.85 +/- 17.41,
      106.19 +/- 15.32, 73.64 +/- 21.02, 35.18 +/- 11.95, 16.27 +/- 9.35 respectively),
      while the IOD of HSP73 did not show any remarkable change (24 h: 102.29 +/-
      21.24, 87.71 +/- 18.70, 71.19 +/- 14.08, 71.87 +/- 15.16, 72.78 +/- 17.31
      respectively; 48 h: 86.66 +/- 16.86, 75.67 +/- 10.61, 66.83 +/- 12.63, 67.29 +/-
      10.26, 91.37 +/- 13.68 respectively). CONCLUSION: BaP can inhibit HSP72
      expression and with certain dose-effect relationship, but cannot affect HSP73
      expression.

PMID- 15555318
TI  - [Role of endothelin in the pathogenesis of pulmonary fibrosis].

PMID- 15555319
TI  - [Relationship of transforming growth factor beta and gene polymorphism to
      fibrosis].

PMID- 15555320
TI  - [Interleukin-1 family and disease of pulmonary fibrosis].

PMID- 15555321
TI  - [Gastric lavage for organophosphate pesticides poisoning patients].

PMID- 15555322
TI  - [Clinical analysis of Staphylococcus aureus resistance to methicillin in patients
      with coal worker's pneumoconiosis complicated by lung cancer].

PMID- 15555323
TI  - [Detection of tuberculosis antibody in patients with coal worker's pneumoconiosis
      complicated by pulmonary tuberculosis].

PMID- 15555324
TI  - [Investigation on 1850 cases of acute pesticide poisoning in Shaoxing city].

PMID- 15555325
TI  - [Relationship between Q-T dispersion and ventricular arrhythmia in patients with
      coal workers' pneumoconiosis].

PMID- 15555326
TI  - [Clinical observation on treatment of retreated positive tubercle bacillus
      pneumoconio-tuberculosis with levofloxacin].

PMID- 15555327
TI  - [How to evaluate the competence in reading chest X-ray film of pneumoconiosis].

PMID- 15555328
TI  - [Experience in treatment of poisonous mushroom collective poisoning].

PMID- 15555330
TI  - [Analysis of gene expression profile in lung adenocarcinoma, tumor adjacent
      tissue and fetal lung tissue].
AB  - OBJECTIVE: To investigate the gene expression profiles in lung adenocarcinoma
      (LA), tumor adjacent tissue (TAT) and fetal lung tissue (FLT) by cDNA microarray
      technique. METHODS: Total RNA from LA, TAT and FLT was extracted and purified.
      The cDNA was made by RT-PCR, and then labeled with Cy5 and Cy3 fluorescence as
      probes which were hybridized with the whole gene chips. Subsequently, the signal
      images were scanned by ScanArray 4000 fluorescence scanner and analyzed by Gene
      Pix PRO3.0. RESULTS: In 4 cases with LA and TAT, 25 genes were screened out for
      differences in gene expression level, among which 3 were upregulated and 22
      downregulated; in FLT and TAT cases, 316 genes were screened out, among which 192
      were upregulated and 124 downregulated; 16 genes were found to be differentially
      expressed genes in common in LA, TAT and FLT, among which 12 were upregulated and
      4 downregulated. CONCLUSION: The 25 differentially expressed genes in LA and TAT
      may be related to occurrence and development of lung cancer, while the 316 genes
      in FLT and TAT may be related to fetal developmental. The 16 differentially
      expressed genes may be related to the initiation of lung cancer.

PMID- 15555331
TI  - [EB virus encoded latent membrane protein 1 mediated expression of transcription
      factor Ets-1 in nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To elucidate the expression of tanscription factor Ets-1 mediated by
      EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma
      (NPC) cells. METHODS: LMP1-expressing NPC HNE2 cells regulated by Tet-on system
      (pTet-on-LMP1 HNE2) were used. Expression of LMP1 and Ets-1 was observed after
      induction with Doxycycline (Dox). Expression of Ets-1 mRNA and protein was
      detected by RT-PCR and Western blot, respectively. The phosphorylation level of
      Ets-1 protein was examined by co-immunoprecipitation. The DNA binding activity of
      Ets-1 was detected by electrophoretic-mobility shift assay (EMSA). RESULTS: After
      induction with Dox in pTet-on-LMP1 HNE2 cells, to some extent, the expression of
      Ets-1 mRNA and protein, its phosphorylation level and DNA binding activity were
      increased with enhancement of LMP1 expression. CONCLUSION: LMP1 induces
      transcriptional activation and expression of Ets-1 which may contribute to the
      development of NPC.

PMID- 15555332
TI  - [Suppression of c-myc expression by interference RNA in HepG2 hepatocellular
      carcinoma cells].
AB  - OBJECTIVE: To study the inhibitory effect of RNA interference (RNAi) on c-myc
      expression in hepatocellular carcinoma cell line, HepG2. METHODS: Expression
      vector of c-myc gene-targeting small interference RNA (siRNA) was constructed
      (psilencer-c-myc) and transfected into HepG2 cells by lipofectamine, and the
      unloaded vector was used as control (mock). The expression of c-myc mRNA and
      protein was identified by quantitive PCR and Western blot. Apoptosis of the
      transfected cells was examined by flow cytometry and immunofluorescent
      microscopy. RESULTS: After HepG2 cells were transfected with psilencer-c-myc, the
      expression of c-myc mRNA and protein was suppressed with an inhibition rate of
      67% compared with the mock-transfected cells. Apoptosis was identified in the
      transfected HepG2 cells. CONCLUSION: The expression of c-myc at transcriptional
      and translational levels in HepG2 cells transfected with siRNA is markedly
      inhibited, which may be associated with the induction of apoptosis.

PMID- 15555333
TI  - [Establishment and characteristics of orthotopically transplanted model of human
      primary malignant small intestinal lymphoma in nude mice].
AB  - OBJECTIVE: To establish orthotopically transplanted model of human malignant
      small intestinal lymphoma in nude mice and analyze their biologic
      characteristics. METHODS: Small intestinal lymphoma tissues from 5 patients were
      transplanted into intestinal mucosa of nude mice. Tumorgenecity, invasion and
      metastasis of the transplanted tumors were observed by morphological analyses
      (light microscopy, electron microscopy and immunohistochemistry), karyotyping and
      DNA quantitative assay. RESULTS: Tumor tissues from 3 lymphoma patients were
      successfully transplanted. According to the World Health Organization
      classification, the three models were classified into non-Hodgkin's lymphoma (B
      cell) of human small intestine (HSIL-1), high metastasis of non-Hodgkin's
      lymphoma (B cell) of human small intestine (HSIL-2) and non-Hodgkin's lymphoma (T
      cell) of human small intestine (HSIL-3), respectively. Immunohistochemistry
      showed that CD19, CD20, CD22, CD40, CD45 and CD72 were positive in HSIL-1 and
      HSIL-2, whereas CD3, CD7 and CD45RO were positive in HSIL-3. The karyotypes of
      the transplanted tumors were all hypotriploid with modal numbers from 55 to 69
      and the DNA index (DI) was 1.46 approximately 1.71. The three models had been
      passaged for 32, 27 and 21 generations respectively in 433 nude mice. The growth
      rate, resuscitation rate of the liquid nitrogen preserved tumor cells and
      spontaneous metastasis rate upon transplantation were all 100%. We observed an
      invasive growth of the transplanted tumors in small intestine, which resulted in
      disrupting of the intestinal wall, hematogenous metastasis, lymph node metastasis
      and seeding metastasis. The features of the transplanted tumors were similar to
      the original tumors in histopathology, ultrastructure, DNA content and karyotype.
      CONCLUSION: Three strains of orthotopically transplanted model of human primary
      malignant small intestinal lymphoma in nude mice were successfully developed. The
      result of research will provide ideal animal models for further studies on
      mechanism of tumorigenesis, invasion and metastasis of malignant small intestinal
      lymphoma and experimental therapy.

PMID- 15555334
TI  - [Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by
      combined treatment with human cytokine-induced killer cells and chemotherapy].
AB  - OBJECTIVE: To compare the inhibitory effects of cytokine-induced killer (CIK)
      cells alone, chemotherapeutic drug alone, and CIK cells combined with
      chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells
      transplanted in nude mice. METHODS: Peripheral blood mononuclear cells (PBMC)
      collected from five healthy donors by blood cell separator were incubated in
      vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2
      and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was
      characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated
      subcutaneously to nude mice. On day 5, at the inoculation site were injected
      normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3),
      mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC
      (group 5), respectively. RESULTS: The percentage of CD3(+), CD3(+)CD8(+),
      CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to
      94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The
      percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during
      incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked
      respectively on day 7 and 13 and then declined. During the 90-day observation,
      the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse
      survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group
      1 to group 5. Compared to the other groups, in the combined therapy group of
      mice, not only the tumor grew slowly and but also showed more marked tissue
      necrosis. CONCLUSION: The growth inhibitory effect on human HCC transplanted in
      nude mice of combined CIK cells and MMC treatment is more potent than that of CIK
      cells or MMC alone.

PMID- 15555335
TI  - [Hypermethylation of the death-associated protein kinase promoter in laryngeal
      squamous cell cancer].
AB  - OBJECTIVE: To explore the relationship between hypermethylation of the promoter
      of death-associated protein kinase (DAPK) gene and laryngeal squamous cell
      cancer. METHODS: Promoter hypermethylation and mRNA expression of DAPK gene were
      detected by methylation-specific PCR, RT-PCR and gene sequencing. RESULTS: Among
      the 58 patients with laryngeal squamous cell cancer, hypermethylation of DAPK
      promoter was detected in 39 cases (67.2%). There was no significant difference in
      hypermethylation in relation to pathological grade and clinical staging, but a
      highly significant difference was observed between patients with and without
      lymph node metastasis (N0 and N1) (P < 0.001). DAPK promoter hypermethylation was
      detected in tumor adjacent tissues in 6 of the 58 cases. DAPK mRNA was not
      expressed in all laryngeal squamous cell cancers having hypermethylation of DAPK
      promoter, whereas it was expressed in normal laryngeal mucosa, laryngeal squamous
      cell cancers without hypermethylation and tumor adjacent tissues. CONCLUSION:
      Hypermethylation of DAPK promoter is associated with loss of its transcription in
      laryngeal squamous cell carcinoma. The high frequency hypermethylation of DAPK
      promoter illustrates its potential clinical application as tumor marker for
      diagnosis and prognosis.

PMID- 15555336
TI  - [The effect of pro-angiogenic factors and their receptors on angiogenesis in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To explore the effect of pro-angiogenic factors and their receptors on
      angiogenesis in hepatocellular carcinoma. METHODS: Expression of VEGF/KDR and
      Angiopoietins/Tie2 was detected by RT-PCR and Western blot in 15 cases with
      hepatocellular carcinoma, 15 tumor adjacent tissues (<1 cm, >5 cm), 8 cirrhotic
      liver, and 4 normal liver. Immunohistochemistry (IHC) was used to detect CD34
      expression, and the relationship between neovascular density and angiogenesis was
      analyzed. RESULTS: The expression levels of VEGF and Ang2 were significantly
      higher in hepacellular carcinoma group than those in the other groups (P < 0.01),
      and so did the expression of CD34. The expressions of KDR and Ang1/Tie2 showed no
      significant difference in all groups, but they indeed increased to various levels
      in tumor and tumor adjacent tissues as compared with those in cirrhosis and
      normal liver. CONCLUSION: VEGF/KDR and Angiopoietins/Tie2 may be the crucial
      signal pathways in the development of hepatocellular carcinoma.

PMID- 15555337
TI  - [Expression and significance of PCNA and p27 in benign prostate hypertrophy and
      prostate carcinoma].
AB  - OBJECTIVE: To investigate the expression of PCNA and p27 in human benign prostate
      hypertrophy (BPH) and prostate carcinoma (PCa) and their effect on the genesis
      and progression of the tumor. METHODS: The paraffin-embedded sections of 30 cases
      with BPH and 37 cases with PCa were collected. The expression of p27 and PCNA
      protein were examined by S-P immunohistochemical method. Comparative analysis for
      BPH and pathological grade and clinical stage of PCa was performed. RESULTS: The
      expression of PCNA in BPH (3.3%) was significantly lower than that in Pca (83.8%,
      P < 0.01). The expression of p27 in BPH (70.0%) was significantly higher than
      that in Pca (27.0%, P < 0.05). The expression of p27 was not correlated with
      histological grade and clinical stage in Pca (P > 0.05). An inverse correlation
      was found between p27 and PCNA expression in BPH (P < 0.01), while no correlation
      was found in Pca (P > 0.05). CONCLUSION: The loss or decreased expression of p27
      protein may be related to the genesis of benign prostate hypertrophy, but not to
      the development of prostate carcinoma; the overexpression of PCNA may play an
      important role in the malignant behavior and progression of prostate carcinoma.

PMID- 15555338
TI  - [Clinical significance of expression of PSA, hK2, PSMA in the peripheral blood of
      patients with prostate cancer].
AB  - OBJECTIVE: To find sensitive and specific micro-metastic markers for prostate
      cancer. METHODS: Using nested reverse transcription-PCR, we examined the
      expression of PSA, hK2 and PSMA mRNA in peripheral blood mononuclear cells of 51
      patients with prostate cancer, 33 patients with benign prostate hyperplasia (BPH)
      and 32 normal young people. RESULTS: The expression rates of PSA, hK2 and PSMA
      mRNA were 52.9%, 43.1% and 64.7%, respectively in prostate cancer group, and
      6.2%, 7.7% and 4.6%, respectively in control group (BPH patients and normal young
      people) with statistical significance (P < 0.01). Although the expression rate of
      PSA and hK2 mRNA increased with cancer progression, there was no statistical
      significance among patients in different stages. The expression rate of PSMA mRNA
      was higher than that of PSA and hK2 mRNA in each clinical stage. CONCLUSION: PSMA
      mRNA expression detected by nested RT-PCR is of greater value for the diagnosis,
      therapy choice and prognostic evaluation of prostate cancer patients.

PMID- 15555339
TI  - [Value of EBNA1-IgA and EA-IgG in serological diagnosis of nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To evaluate the value of EBNA1-IgA and EA-IgG in serological diagnosis
      of nasopharyngeal carcinoma (NPC). METHODS: The serum EBNA1-IgA and EA-IgG of 56
      patients with NPC and 58 healthy adults were detected by ELISA. The sensitivity,
      specificity, positive predictive value, accuracy rate and odds ratio of the two
      tests used singly or in combination were compared with each other. RESULTS: The
      sensitivity of EBNA1-IgA (91.07%) was higher than that of EA-IgG (87.50%), while
      the specificity of EA-IgG (87.93%) was higher than that of EBNA1-IgA (84.48%).
      The combination of EBNA1-IgA and EA-IgG could enhance the specificity (94.83%),
      positive predictive value (0.9375), likelihood ratio (15.5435) and odds ratio
      (75.0000) for serological diagnosis of NPC. Forty-five patients showed both
      positive EBNA1-IgA and positive EA-IgG. A positive EA-IgG was detected in 4 out
      of 5 patients with negative EBNA1-IgA and a positive EBNA1-IgA was founded in 6
      out of 7 patients with negative EA-IgG. CONCLUSION: Although relatively high
      sensitivity and specificity could be obtained by either EBNA1-IgA or EA-IgG test
      alone, the combination of these two tests with a complementary effect is able to
      enhance the reliability of serological diagnosis of NPC as most patients have
      positive ENBA1-IgA and EA-IgG concurrently.

PMID- 15555340
TI  - [Diagnosis, treatment and prognostic factors of adenoid cystic carcinoma of the
      palate].
AB  - OBJECTIVE: To explore the clinical characteristics, diagnosis, treatment and
      prognosis of adenoid cystic carcinoma of the palate. METHODS: A retrospective
      review was conducted in 42 patients with adenoid cystic carcinoma of the palate
      treated in our hospital from 1967 to 1998. Statistical analysis was performed
      using the Kaplan-Meier method. Prognostic factors were analyzed by Log Rank test.
      RESULTS: The overall 5-, 10-, 15-year accumulative survival rates were 85.0%,
      61.8% and 28.1%, and the 5-, 10-, 15-year accumulative disease-free survival
      rates were 52.4%, 32.7% and 22.4%, respectively. The 5-, 10-, 15-year
      accumulative local recurrence rates were 25.2%, 50.9% and 73.1%, and the 5-, 10-,
      15-year accumulative distant metastasis rates were 28.5%, 50.4% and 66.0%
      respectively. T stage, bone invasion, extent of tumor, local recurrence and
      distant metastasis were significant prognostic factors. Treatment method, dose
      and area covered by radiotherapy were related to the prognosis. CONCLUSION:
      Surgery alone can be done for early lesions, and combination of surgery with
      radiotherapy should be adopted for advanced lesions in adenoid cystic carcinoma
      of the palate. Radiotherapic salvage could prolong the survival of the locally
      recurrent patients.

PMID- 15555341
TI  - [Prognostic factors of stage IB and IIA carcinoma of the cervix treated by
      surgery].
AB  - OBJECTIVE: To evaluate prognostic factors in patients with stage IB-IIA of
      cervical carcinoma treated by surgery. METHODS: Between December 1992 and
      December 2001, 111 patients with stage IB-IIA cervical cancer surgically treated
      were analyzed. Median age 40 years. According to 1994 FIGO Staging System: IB 80
      (IB1 40, IB2 40) and IIA 31. There were 93 cases of squamous cell carcinoma
      (83.5%), 17 cases of adenocarcinoma (15.3%) and one case of small cell carcinoma.
      All patients were treated by radical hysterectomy and pelvic lymphadenectomy, 74
      patients had preoperative adjuvant radiotherapy, 24 patients had postoperative
      adjuvant treatment. Kaplan-Meier method was used to evaluate the survival, the
      related prognostic factors were assessed by Cox regression and chi(2) test.
      RESULTS: The overall 5-year survival rate was 85.9%, being 89.1%, 90.7% and 78.4%
      for stage IB1, IB2 and IIA, respectively. Univariate analysis showed that tumor
      size (hazards ratio [HR] = 1.479, P = 0.152), tumor type (HR = 1.440, P = 0.264),
      clinical stage (HR = 1.380, P = 0.354), adjuvant treatment (HR = 1.210, P =
      0.450), lymph node metastasis (HR = 1.432, P = 0.540), endocervical involvement
      (HR = 2.244, P = 0.036), depth of myometrial invasion (HR = 3.295, P = 0.06) and
      multiple sexual partners during pregnancy (HR = 10.172, P = 0.000) were of
      prognostic significance. The latter two were the most important factors
      indicative of poor prognosis. CONCLUSION: The depth of myometrial invasion and
      multi-partners combined with pregnancy are closely related to the prognosis while
      the pre- and/or postoperative adjuvant therapy should be considered for stage IB
      IIA cervical cancer with deep myometrial invasion and in pregnant patients with
      multiple sexual partners.

PMID- 15555342
TI  - [Neoadjuvant chemotherapy for primary breast cancer].
AB  - OBJECTIVE: To evaluate the feasibility and effect of fluorouracil (5-Fu) in
      association with anthracycline-based regimen as neoadjuvant chemotherapy for
      primary breast cancer. METHODS: For one hundred and eleven primary breast cancer
      patients with 114 lesions who were to be operated, two to six cycles of 5-Fu
      (continuous infusion) in association with epirubicin or pirarubicin and
      cyclophosphamide (CEFci or CTFci regimen) were given before operation. The
      response rate, side effect and its relation with tumor characteristics were
      studied. RESULTS: The overall response rate was 87.7%, of which the complete
      clinical response was 39.5%, pathological complete response was 23.7%, only one
      patient (0.9%) showed progressive disease. The regimen containing pirarubicin was
      superior to epirubicin regimen in pathological complete response rate (P < 0.05).
      Alopecia was mild in pirarubicin regimen as compared with epirubicin regimen but
      neutropenia was more severe in pirarubicin regimen than that in epirubicin
      regimen. Hormonal receptor expressions were significantly related to treatment
      response, the pathological complete response rate was 33.3% in oestrogen or
      progestin receptor negative tumors, but it was 7.5% in the positive tumors (P <
      0.005). No correlation was observed between treatment response and tumor size, as
      well as HER-2 expression. CONCLUSION: CTFci/CEFci regimen as neoadjuvant
      chemotherapy is effective and safe for primary breast cancer. CTFci regimen is
      superior to CEFci regimen in response rate. The patients with negative hormonal
      receptor are more sensitive to the neoadjuvant chemotherapy.

PMID- 15555343
TI  - [Prospective randomized trial of RFA and chemotherapy for unresectable small
      hepatocellular carcinoma].
AB  - OBJECTIVE: To study the clinical safety and effect on local recurrence in
      unresectable small hepatocellular carcinoma treated by radiofrequency ablation
      (RFA) with and without chemotherapy through a prospective randomized trial.
      METHODS: Thirty-eight unresectable small hepatocellular carcinoma patients with
      diameter </= 3 cm were selected, of which 27 patients have been followed up for 1
      year. Through a prospective randomized trial, 12 patients were in the RFA group
      and 15 patients in the RFA combined with systemic chemotherapy group. RFA was
      given image-guided. The regimen of systemic chemotherapy: EADM 50 mg on day 1, 3;
      CDDP 40 mg on day 1, 3 and FUDR 500 mg on day 1, 2, 3. After RFA treatment, liver
      function, WBC count and complications were observed on day 1, 4, 7; CT scan was
      performed in 1, 6, 12 months. The safety and local recurrence were analyzed.
      RESULTS: There was no local recurrence of the tumor in the two groups 1 month
      after RFA treatment. The 6- and 12-month local recurrence rates were
      significantly lower in the combined group than that in RFA group alone (P <
      0.01). There were no severe complications in the two groups, and nor was there
      any significant difference in liver function and WBC count. CONCLUSION: RFA
      combined with systemic chemotherapy is safe, and it can reduce the local
      recurrence of unresectable small hepatocellular carcinoma </= 3 cm in diameter.

PMID- 15555344
TI  - [Retroperitoneal lymph node metastasis in epithelial cancer of the ovary: a
      report of 58 cases].
AB  - OBJECTIVE: To analyze the retroperitoneal lymph node metastasis in epithelial
      cancer of the ovary and offer scientific indications for lymph node radical
      dissection. METHODS: Fifty-eight patients with ovarian cancer treated from
      January 1990 to December 2000 were retrospectively reviewed. Single-factor and
      multifactor analysis with Logistic regression model were performed by SPSS 10.0
      statistic software. RESULTS: The metastasis rates of overall lymph nodes, pelvic
      nodes and para-aortic nodes were 48.3%, 37.9% and 25.9% respectively, among which
      no significant difference was noted (P > 0.05). Single-factor analysis showed
      that tumor location, ascitic condition, clinical stage and the size of residual
      tumor were associated with retroperitoneal lymph node metastasis. Multifactor
      analysis revealed that clinical stage and size of residual tumor were independent
      risk factors for metastasis of retroperitoneal lymph nodes. CONCLUSION: For early
      ovarian cancer patients, it is extremely important to perform radical dissection
      of the retroperitoneal lymph nodes. For advanced or residual lesions, radical
      dissection of pelvic nodes and para-aortic nodes could be considered in the
      second exploration.

PMID- 15555345
TI  - [The analysis of different treatment methods for 184 cases of soft tissue
      sarcoma].
AB  - OBJECTIVE: To study the proper way of using combined postoperative chemo
      radiotherapy and prognostic factors of soft tissue sarcoma. METHODS: The clinical
      data of 184 patients were retrospectively reviewed. These patients were devided
      into surgery group (S, 94 patients), surgery plus postoperative radiotherapy
      group (S + R, 62 patients) and surgery plus chemotherapy group (S + C, 28
      patients). RESULTS: The 5-year survival rates of S, S + R and S + C groups were
      39.4%, 48.4% and 28.6%, respectively. Combined multitherapy was the key to
      improve survival rate and life quality. Clinical stage, pathological type and
      therapeutic method were also important prognostic factors for the long term
      survival. CONCLUSION: Surgery plus postoperative radiotherapy can improve the 5
      year survival rate of soft tissue sarcoma.

PMID- 15555350
TI  - [Epidemiological study on rotavirus-borne diarrhea in infants and children in
      different areas].
AB  - OBJECTIVE: To analyze and compare the epidemiological features of rotavirus
      diarrhea among infants in the different areas so as to provide data for rotavirus
      vaccine research. METHODS: From Sep. 2001 through Sep. 2003, sentinel sites were
      set up in Suzhou Children's Hospital and Maanshan Hospital. Fecal samples from
      children (< 5 years) with acute diarrheal were collected and enzyme linked
      immunosorbent assay was used to detect rotavirus antigen. Reverse transcription
      polymerase chain reaction was used to determine the G serotypes and P genotypes
      of rotavirus strains. The features of strains in the two places and other areas
      of China were analyzed and compared. RESULTS: (1) Rotavirus infection appeared in
      autumn and winter, but the peaks varied. In Suzhou the peaks were from December
      to next February in 2001, and November to next January in 2002. But in Maanshan,
      it was November to next January for both two years. (2) Rate of rotavirus
      infection in Suzhou was much higher than that in Maanshan, infective rates of
      Inpatient Department and Outpatient Department are 47.28%, 28.39% and 30.38%,
      14.77% respectively in the two hospitals. (3) Rates of infection in two hospitals
      showed age difference but the highest group was in 6 - 35 month-olds. No gender
      difference was found. (4) Secular distribution of G-typing and P-typing of
      rotavirus strain was different in Suzhou and Maanshan. G3 was mainly found in
      Suzhou and G1 in Maanshan. From 2002-2003 on, G3 became dominant in Maanshan.
      CONCLUSION: Rotavirus caused diarrhea among infant and children were different in
      terms of areas, period and types, suggesting that the introduction of rotavirus
      vaccine should be adjusted according to different strains with specific types and
      optimal timeline.

PMID- 15555351
TI  - [A case-control study on the risk factors of severe acute respiratory syndromes
      among health care workers].
AB  - OBJECTIVE: To study the factors in relation to severe acute respiratory syndromes
      (SARS) among health care workers and to develop related protective measures.
      METHODS: Case-control study was applied. A standardized questionnaire was used to
      collect SARS related information for health care workers who had contacted or
      treated SARS patients. Univariate analysis was conducted using SPSS 10.0 software
      package and multivariate logistic regression analysis was conducted using SAS
      6.12. RESULTS: Twenty-seven of the 49 factors under study were significantly
      associated with SARS infection, in which 22 factors were protective, and the
      other 5 were risk factors. 27 factors were included for multivariate logistic
      regression analysis. Results showed that six factors as wearing eye glasses,
      wearing protection gowns, exposure to secrets/mode of contact with SARS patients,
      types of mask and the working years atc, remained significant association with
      hospital infection of SARS. CONCLUSION: SARS infection in heath care workers was
      related to many factors during the process of diagnoses and/or treatment. It is
      recommended that adequate masks, eye-protection and protective gowns should be
      adopted for heath care workers during the process of clinical diagnoses and
      treatment of SARS patients.

PMID- 15555352
TI  - [Study on the prevalence of tic disorders in schoolchildren aged 7-16 years old
      in Wenzhou].
AB  - OBJECTIVE: To study the epidemiological features of tic disorders (TD) among
      schoolchildren in Wenzhou area. METHODS: Stratified cluster sampling was carried
      out to investigate TD in 9742 schoolchildren aged 7 to 16 years old in Wenzhou.
      RESULTS: The average prevalence rate of TD among school-age children was 104/10
      000 (166/10 000 for males, 29/10 000 for females). There was a significantly
      higher prevalence rate for males than that for females (chi(2) = 43.96, P <
      0.001, prevalence ratio = 5.7, prevalence ratio 95% CI: 3.20 - 10.30). The
      prevalence rates of clinical subtypes in males was significantly higher than that
      of females while pupils was significantly higher than that in high school
      students (chi(2) = 11.33, P < 0.01, prevalence ratio = 2.2, prevalence ratio 95%
      CI: 1.37 - 3.43). Prevalence rate of transient tic disorders (TTD), chronic motor
      vocal tic disorder (CMVTD), tourette syndrome (TS) were 34/10 000, 27/10 000 and
      43/10 000 respectively with the highest among 9-10 years old group. The mean
      onset age of TD was 8.5 +/- 2.8 years. The peak of onset was among 6-10 year
      olds. The rate of delayed diagnosis of the disorders was 69.3% and the median in
      delayed diagnosis was 1.0 year. CONCLUSION: TD is a common disease with high rate
      of misdiagnoses among schoolchildren in Wenzhou area. Physicians and population
      should be trained to identify the syndromes and to practice correct diagnosis and
      effective treatment as early as possible.

PMID- 15555353
TI  - [A prospective cohort study on the comparison of risk of occupational dust
      exposure and smoking to death].
AB  - OBJECTIVE: To compare the effects of dust exposure and smoking on mortality.
      METHODS: Based on the Guangzhou Occupational Health Surveillance Record System
      established in 1989-1992, 80 987 factory workers, aged > or = 30, occupationally
      exposed to dust and non-exposure to dust, were included in a prospective cohort
      study. RESULTS: (1) The mean age of the cohort was 43.5. Most subjects were
      workers, with secondary education, and married. Out of them 16.3% having ever
      exposed to dust, 43.7% ever smoked and 33.5% drank alcohol. (2) The cohort were
      traced for 8 years on average, but 35 were lost for follow-up. Malignant neoplasm
      was most commonly seen among 1539 deaths. (3) The adjusted relative risk (RRs) of
      death of all causes, malignant neoplasm and cerebro-cardiovascular diseases for
      dust exposed workers were close to those for smokers. However, the adjusted RRs
      of death of nasopharynx cancer and respiratory system diseases for dust exposed
      workers were higher than those for smokers. The adjusted RRs of death of lung
      cancer and stomach cancer for smokers were 2.2 times and 1.5 times of that for
      dust exposed workers respectively. Dust exposure combined with smoking caused
      significantly higher death RR. (4) In males, the adjusted RRs of death of all
      causes, malignant neoplasm and respiratory system diseases for silica dust
      exposed workers and the adjusted RR of death of cerebro-cardiovascular diseases
      for wood dust exposed workers were higher those in smokers. (5) The population
      attributable risk percentage (PARP) of all causes of death for smokers was 2.5
      times of that for dust exposed workers. (6) In males, the risks of death for all
      causes, malignant neoplasm, lung cancer and stomach cancer increased with the
      amount of smoking per day and the duration of smoking. The risks of death caused
      by coronary heart disease and respiratory system diseases were increasing with
      the amount of smoking per day and the duration of smoking respectively.
      CONCLUSIONS: The adjusted RRs for dust exposed workers were close to those for
      smokers with dust exposure and smoking having synergistic effects. Some of the
      adjusted RRs for smokers were higher than those for dust exposed workers PARP for
      smokers was higher than that for dust exposed workers. Our findings suggested
      that there was a significant dose-effect between smoking and risk of deaths.

PMID- 15555354
TI  - [Prevalence of seronegative spondyloarthritis in the army force of China].
AB  - OBJECTIVE: To investigate the prevalence and epidemiologic characteristics of
      seronegative spondyloarthritis (SpAs) in Chinese army force in different areas.
      METHODS: 4-phase survey was conducted in 21 750 Chinese army, including: face-to
      face interviews with standardized COPCORD questionnaires (Phase I screening);
      further examination on the suspected cases; identification of inflammatory joint
      and spinal diseases (Phase II); identification of SpAs (AS and uSpA) by more than
      two experienced specialists in rheumatology; further examination with X-rays and
      laboratory detection of HLA-B27 (Phase III); and data analysis (Phase IV).
      RESULTS: Among 21 750 army men, 21 cases of RA, 106 cases of SpAs were
      identified, with prevalence rates of 0.966 per thousand, 4.87 per thousand
      respectively. In 106 cases of SpAs, there were 46 cases of ankylosing spondylitis
      (AS), 52 cases of undifferentiated SpAs (uSpAs) with the prevalence rates of 2.11
      per thousand and 2.39 per thousand respectively. Few cases of reactive arthritis
      (ReA) and Reiter's syndrome (RS) were identified (6 and 1 cases respectively).
      The prevalence of AS, uSpAs were higher in navy than that in the ground force or
      the air force. Soldiers in cold and damp areas had higher prevalence rates than
      that in the plain and drought areas. CONCLUSION: The prevalence of SpA
      (especially AS and uSpA) in Chinese army force was similar to that in the
      civilians. SpA (AS and uSpA) was more prevalent seen in the Navy. The incidence
      of SpA (AS and uSpA) was influenced by environmental factors such as coldness and
      dampness.

PMID- 15555355
TI  - [Association between angiotensin converting enzyme gene, chymase gene and
      regression of left ventricular hypertrophy in patients treated with angiotensin
      converting enzyme inhibitors].
AB  - OBJECTIVE: To investigate the association between insertion/deletion (I/D)
      polymorphism of the angiotensin converting enzyme (ACE) gene and the A/B
      polymorphism of the chymase (CMA) gene with regression of left ventricular
      hypertrophy (LVH) in patients with essential hypertension and left ventricular
      hypertrophy. The study subjects had been participants in along-term trial of
      therapy with an ACE inhibitor. METHODS: Follow-up data of 157 patients with
      essential hypertension and left ventricular hypertrophy were collected. DNA
      fragments of ACE gene and CMA gene were amplified by PCR and analysed by RFLP.
      LVDd, IVST and LVPWT were measured by Ultrasonic Cardiogram (UCG). RESULTS: (1)
      When long-term treatment with Benazepril was carried out, the blood pressure was
      markedly decreased and the heart rate was maintained steadily. (2) Regression of
      left ventricular hypertrophy was improved. (3) The magnitudes of regression of
      LVM and LVMI during therapy were greater in the DD group than in the II and ID
      group. No significant differences of other indices were found in the different
      genotype groups of ACE. (4) No significant differences of all indices were found
      in the different genotype groups of CMA. (5) No interaction appeared between the
      genotypes of the ACE and the genotypes of the CMA. CONCLUSION: Hypertensive
      patients with DD genotype were more likely to have regression of left ventricular
      hypertrophy when treated with ACE inhibitors than patients with other ACE
      genotypes. No evidence was found to support an association between CMA genotype
      and regression of LVH in those patients.

PMID- 15555356
TI  - [Study on AIDS related risk behaviors and the correlated factors among three
      groups of population in Sichuan province].
AB  - OBJECTIVE: To provide the basis for AIDS intervention, the study on the
      relationship between AIDS related risk behaviors and the related factors was
      carried out among prostitutes, injection drug users and long-distance truck
      drivers. METHODS: Questionnaire investigation and statistical analysis as chi(2)
      test, F test, logistic regression were adopted to analysis the relationship
      between AIDS related risk behaviors and the correlated factors. RESULTS:
      Knowledge about AIDS seemed to be related to their level of understanding the
      problem (in commercial sex workers r = 0.307, P = 0.000, in injection drug users
      F = 93.07, P = 0.000, in truck man F = 30.06, P = 0.000). Condom use when
      entertaining their clients last time was related to the knowledge of HIV
      transmission in commercial sex workers and truck drivers (OR = 1.171, 1.145) and
      knowledge of HIV prevention (OR = 1.081, 1.397), in drug users regarding gender
      difference (OR = 2.121). CONCLUSION: This study addressed that the effective
      means to reduce the rate of AIDS risk behaviors and to lessen the harm of AIDS
      are to improve the knowledge of AIDS and the effective methods to prevent AIDS in
      the high risk population.

PMID- 15555357
TI  - [Significance of p53 gene mutation and P53 protein expression abnormality on the
      prognosis of esophageal cancer: a meta-analysis study].
AB  - OBJECTIVE: To evaluate the prognostic significance of p53 mutation and P53
      protein expression abnormality among esophageal cancer. METHODS: The results of
      27 random controlled trials from 1990 to 2003 were analyzed by meta-analysis
      method. The overall positive rate of p53 was 52.9% among the cumulative 2174
      cases. Relative hazard (RH) was applied to evaluate the risk of disease and all
      data were analyzed by Dersimonian-Laird method. RESULTS: The analysis for
      homogeneity (q statistics test) showed that all eligible studies were with
      heterogeneity (q = 59.88, P < 0.005). The combined RH was 2.07 and 95% confidence
      interval was 1.58-2.70. CONCLUSION: Findings showed that p53 was a poor prognosis
      biomarker for esophageal cancer gene diagnosis but might benefit to the strategy
      of treatment.

PMID- 15555358
TI  - [Meta-analysis on the relationship between tobacco smoking, alcohol drinking and
      p53 alteration in cases with esophageal carcinoma].
AB  - OBJECTIVE: To investigate the relationship between tobacco smoking, drinking and
      p53 alteration in esophageal carcinoma. METHODS: Literature on the relationship
      between p53 alteration in esophageal carcinoma and tobacco smoking, drinking
      through Meta-analysis were reviewed. RESULTS: In 14 selected papers related to
      tobacco smoking, pooled odds ratio (OR) of tobacco smoking with P53
      overexpression and p53 alteration were 1.99 (95% CI: 1.30- 3.06) and 1.64 (95%
      CI: 1.13 - 2.37), respectively (P < 0.05). Pooled OR of tobacco smoking with p53
      mutation was 1.11 (95% CI: 0.47 - 2.76) (P > 0.05). In 11 selected papers on
      alcohol drinking, pooled OR of drinking with P53 overexpression, p53 mutation and
      p53 alteration were 1.30 (95% CI: 0.83 - 2.04), 1.13 (95% CI: 0.67 - 1.90) and
      1.22 (95% CI: 0.87 - 1.72) respectively (P > 0.05). CONCLUSION: There were
      significant relations between tobacco smoking and p53 alteration while there were
      no significant relations between alcohol drinking and p53 alteration.

PMID- 15555359
TI  - [Application of random amplification polymorphic DNA in the genotyping of
      Neisseria gonorrhoeae].
AB  - OBJECTIVE: To set up random amplified polymorphic DNAs (RAPD) method in
      genotyping Neisseria gonorrhoeae on DNA level, and to explore its use to trace
      the source of infection. METHODS: Four different pretreatments were used to
      extract the Neisseria gonorrhoeae genomic DNA with its advantages and
      disadvantages compared. Arbitrary sequence was then used to amplify the genomic
      DNA of Neisseria gonorrhoeae and RAPD fingerprint maps was applied to distinct
      the Neisseria gonorrhoeae strains. Finally, RAPD fingerprint of Neisseria
      gonorrhoeae strain between patient and his/her sexual partner was compared.
      RESULTS: Cetyltrimethylammonium bromide method was classical in extracting
      genomic DNA, and could get integrated genomic DNA and good fingerprint maps,
      since main segments were common to all the Neisseria gonorrhoeae but some were
      different among strains so that the fingerprint of different Neisseria
      gonorrhoeae were distinctive. However, fingerprint maps of Neisseria gonorrhoeae
      collected from sex partners were quite similar. CONCLUSION: Based on genomic
      levels, effective fingerprint maps could be identified and to classify the
      Neisseria gonorrhoeae into different genotypes. RAPD fingerprint maps could be
      used to trace the source of infection.

PMID- 15555360
TI  - [Cloning and expression of flagellin gene from a Chinese Borrelia burgdorferi
      PD91 strain].
AB  - OBJECTIVE: To study the cloning and expression of flagellin gene from Chinese
      Borrelia burgdorferi, PD91 strain and to evaluate the feasibility of using
      recombinant protein as diagnostic antigen when comparing the gene sequence with
      flagellin gene from North American Borrelia burgdorferi B31. METHODS: The piece
      of genes coding flagellin from Chinese Borrelia burgdorferi PD91 by polymerase
      chain reaction (PCR) method was obtained, and constructed recombinant plasmid,
      before transformed into E. coli BL21 strain, and induced. The recombinant plasmid
      was identified with enzyme cutoff and gene sequence comparison. Efficient
      expression strain was selected and the expression product was analyzed with
      sodium amplified polymorphic-polyacrylamide gel electrophoresis (SDS-PAGE) and
      Western-blot method. RESULTS: The recombinant protein (r-flagellin) expressed in
      host bacteria was successful. By means of western-blot assay, the immunological
      response showed the same antigenicity between r-flagellin and PD91 flagellin. The
      piece of genes coding flagellin of PD91 was 1011 bp, but when comparing with that
      of North American Borrelia burgdorferi it showed 94.70% homology. Homology
      between the sequence of amino acid of the r-flagellin and that of B31 flagellin
      was 95.85%. CONCLUSION: Flagellin gene of Borrelia garinii of Chinese Lyme
      disease spirochete was successfully cloned and expressed for the first time. It
      was proved that the immunoreactivity of r-flagellin was the same as the natural
      flagellin.

PMID- 15555361
TI  - [Searching for a schizophrenia susceptibility gene in the 22q11 region].
AB  - OBJECTIVE: To investigate the genetic association for schizophrenia within the
      long arm region 1 band 1 of chromosome 22 (22q11) in a Han Chinese population.
      METHODS: Polymerase chain reaction (PCR)-based restriction fragment length
      polymorphism (RFLP) analysis was used to detect three single nucleotide
      polymorphism (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change)
      present in the ARVCF (armadillo repeat gene deletion in velocardiofacial
      syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed
      sequence tags, EST) locus, among 100 nuclear families composed of fathers,
      mothers and affected offspring with schizophrenia. Genotyping data were analyzed
      by linkage disequilibrium methods including haplotype relative risk (HRR)
      analysis, transmission disequilibrium test (TDT) and haplotype transmission
      analysis. RESULTS: The genotype frequency distributions of three SNPs were all in
      Hardy-Weinberg equilibrium; Both HRR and TDT analysis showed that rs165815 was
      associated with schizophrenia (P < 0.05), whereas the other two SNPs did not show
      any allelic association. The haplotype transmission analysis showed a biased
      transmission for the rs165655-rs165815 haplotype system and for the rs756656
      rs165655-rs165815 haplotype system (P < 0.01). CONCLUSION: Either ARVCF gene
      itself or a nearby locus might confer susceptibility to schizophrenia in a Han
      Chinese population.

PMID- 15555362
TI  - [Assessment on the reliability and validity of the Dermatology Life Quality Index
      in Chinese version].
AB  - OBJECTIVE: Since the dermatology life quality index (DLQI), a self-administered
      general dermatology quality of life instrument, was originally developed and
      published in a dermatology clinic at University hospital of Wales, our goal was
      to popularize the disease-specific scale used in measuring the quality of life of
      patients with skin diseases and to assess the reliability and validity of its
      Chinese version. METHODS: We administered the DLQI to 236 out-patients attending
      our dermatology clinic and results that had been found by those who originated
      the DLQI, were examined. The reliability and validity of DLQI were assessed by
      means of reliability analysis and factor analysis. RESULTS: Overall, the DLQI
      seemed easy to administer and could be completed within 3 minutes. The internal
      consistency coefficient rates of this unidimensional measure were 0.87
      (Cronbach's alpha) and 0.85 (Spearman-brown, s) with high inter-correlations
      found between the dimensions with a correlation coefficient ranging from 0.4024 -
      0.6569. Factor analysis resulted in a unidimensional pattern, which supported the
      use of a total DLQI-C score. CONCLUSION: DLQI was an easy and efficient
      instrument for assessing the quality of life in patients with dermatological
      problems and with better reliability and validity. Thus, it could be used in both
      research and clinical settings in China.

PMID- 15555363
TI  - [A case-control study on the risk factors of central nervous system congenital
      malformations].
AB  - OBJECTIVE: To determine the risk factors in the development of central nervous
      system (CNS) congenital malformations. METHODS: A hospital-based 1:2 matched case
      control study was conducted. Each case was matched with two normal controls on
      sex and residential area, date of birth, within half a year. By means of simple
      and multivariable conditional logistic regression, 48 factors were analyzed.
      RESULTS: Maternal exposure to pesticide or having cold with fever, family history
      of positive congenital malformations, preference eating pickled vegetables,
      negative life events, large consumption of meat, eggs, beans and milk during
      pregnancy and paternal exposure to poisonous chemicals were significantly
      associated with CNS congenital malformations, with odds ratios 16.471, 12.621,
      10.246, 7.274, 3.730, 0.229, 5.616, respectively. CONCLUSIONS: Maternal exposure
      to pesticides, cold with fever, positive congenital malformations family history,
      preference of eating pickled vegetables, negative life events during pregnancy,
      and paternal exposure to poisonous chemicals were the key risk factors
      contributing to CNS congenital malformations, while maternal exposure to big
      consumption of meat, eggs, beans and milk during pregnancy was protective factors
      that reducing CNS congenital malformations.

PMID- 15555364
TI  - [A questionnaire investigation on the way of delivery and its related factors in
      415 women at child bearing age in one hospital].
AB  - OBJECTIVE: To understand the changing trend on the way of delivery since 1970s
      and its related factors that influencing the attitude of choice on Cesarean
      section (C-section) in women at child-bearing age. METHODS: A face-to-face
      interview was conducted anonymously in pregnant and lying-in women visited at the
      out-patient department of Gynecology and Obstetrics, Tiantan Hospital of Beijing.
      Totally, 415 women at child-bearing age, with a history of previous birth were
      interviewed on date, place and way of delivery of last birth, as well as on
      information that could have had impact on the choice of C-section. RESULTS: The
      average rate of C-section in Tiantan Hospital had been 29% since the year of
      2000, much higher than that during 1970s, 1980s and 1990s (chi(2) = 22.81, P =
      0.001) which showed an increasing trend. Rate of C-section among lying-in women
      with native Beijing origin was 25.0%, significantly higher than 9.6% (chi(2) =
      21.96, P = 0.000 002) that in the migrants. Lying-in women with education level
      of high school or above had higher chance to choose C-section than those with
      lower level of education (chi(2) = 43.64, P < 0.000 01). Workers, managerial
      staff or clerks had more chance to choose C-section than those with other
      occupations (chi(2) = 20.07, P = 0.01). As reported by the interviewees, 93%
      (70/75) of C-section in the hospital were performed and recommended by
      obstetricians. CONCLUSION: Rate of C-section in the hospital showed an increasing
      trend which suggested that intervention with health education be carried out for
      both pregnant women and obstetricians.

PMID- 15555365
TI  - [Comparison between tow methods of acute physiology and chronic health evaluation
      III and acute lung injury scale to evaluate the severity and prognosis of severe
      acute respiratory syndrome].
AB  - OBJECTIVE: To evaluate the acute physiology and chronic health evaluation III
      (APACHE III) and acute lung injury (ALI) scale in the severity and prognosis of
      severe acute respiratory syndrome (SARS). METHODS: The clinical data of 38 SARS
      patients, including survivors (24 cases) and no survivors (14 cases) were
      collected and evaluated with APACHE III and ALI scoring systems. The correlation
      of scores and prognosis was evaluated. RESULTS: The scores of APACHE III in the
      non survivors were higher remarkably than those in the survivor group (P <
      0.001). The scores of APACHE III had positive correlation with the overall
      fatality rate. When the scores of APACHE III was higher than 60, the mortality
      increased obviously (chi(2) = 3.886, P < 0.05). Elderly patients with SARS who
      were over 60 years old had a high mortality (chi(2) = 8.660, P < 0.05). The
      scores of ALI in the non survivors had not statistical significance than those in
      the survivor group (P = 0.127). CONCLUSIONS: The score of APACHE III in the SARS
      are correlated with the patient's condition and prognosis. Elderly patients with
      SARS have a high mortality.

PMID- 15555366
TI  - [Application of exponent curve model to study the hepatitis B DNA recombinant
      yeast derived vaccine antibody levels].
AB  - OBJECTIVE: To introduce exponent curve model methods in the study of the
      hepatitis B vaccine antibody level. METHODS: After the China made vaccine of
      hepatitis B DNA recombinant yeast derived vaccine (YDV) had been carried out for
      5 years, data on the anti-HBsAg's titer were used to construct an exponent curve
      model. When the vaccination program had been carried out for 8 years, the
      predicating results of the model were further tested by observed number. RESULTS:
      The exponent curve model was Y = 165.67 exp (-0.019X) and the R(2) was 0.98.
      After 8 years, the practical observed number became 35 mIU/ml, and the
      predicating result of the model was 27 mIU/ml, 8 mIU/ml lower than the observed
      number. When the vaccine had been carried out for 12 years, the predicating
      results of the model became 10.74 mIU/ml, still higher than 10 mIU/ml but was
      still in the effective range. CONCLUSION: An exponent curve model could be
      constructed, as long as the data of the antibody's titer was in accordance with
      the tendency of exponent curve. The model could be used to predict the
      persistence lever of vaccine antibody under certain conditions. The results
      showed that after 8 years, the predicting results of the model were reliably
      lower than the observed number.

PMID- 15555367
TI  - [Advances in the study of relation between mutation of chromosome 22q and
      schizophrenia].

PMID- 15555368
TI  - [Bias and confounding in the epidemiologic studies].

PMID- 15555369
TI  - [Some methodologic issues in the study of injury epidemiology].

PMID- 15555370
TI  - [Hypertension survey in Yi ethnic group in Yunnan Province, China].

PMID- 15555371
TI  - [Molecular epidemiological study of adult rotavirus infection diarrhea in Wuhan
      City].

PMID- 15555372
TI  - [Preliminary study on polymorphism of GSTM1, CYP2E1 and NQO1 genes and risk
      factors of children leukemia].

PMID- 15555373
TI  - [Expression of main protein antigen of Helicobacter pylori and serum antibody in
      infected patients].

PMID- 15555374
TI  - [Systemic lupus erythematous infected with Mycoplasma--120 cases analysis ].

PMID- 15555375
TI  - [Disease burden of malignant tumor in urban in City Hanzhou].

PMID- 15555376
TI  - [Isolation of Legionella pneumophila from water in air conditioning equipment for
      the first time in Zhejiang Province].

PMID- 15555377
TI  - [7th International Injury Prevention and Safety Promotion Congress].

PMID- 15555378
TI  - [Meteorological factors and measles outbreak].

PMID- 15555379
TI  - [Epidemiologic factors of hemorrhagic fever with renal syndrome in Ganyu County
      Jiangsu Province].

PMID- 15555380
TI  - [Epidemiologic survey of outbreak of rubella in Nanjing City].

PMID- 15555381
TI  - [Challenges faced with China tuberculosis control].

PMID- 15555382
TI  - [Analysis on the relationship between tuberculosis case detection and short
      course coverage of directly observed treatment in China].
AB  - OBJECTIVE: To analyze factors influencing tuberculosis (TB) case detection so as
      to predict the trend of case detection in the year of 2005. METHODS: Data was
      collected and analyzed regarding the correlation between the registration rate of
      newly identified smear-positive TB case and the directly observed treatment short
      course (DOTS) coverage from 1996 to 2003. Based on the correlation analysis,
      regression equation was built to predict the case registration rate in 2005.
      RESULTS: Both case registration rate and case detection rate showed an increasing
      trend from 1996 to 1998 and kept a platform between 1999 and 2002, followed by a
      zooming change in 2003 to reach a 45% case detection rate while the smear
      positive TB case registration rate and DOTS coverage showed highly correlative (r
      = 0.849, P = 0.008). The regression equation was: y = b(0) + b(1) X = 1.754 +
      0.217X (95% CI of beta: 0.082 - 0.352), F = 15.43, P = 0.008; R(2) = 0.72. If the
      DOTS coverage rate reaches 100% in 2005, the national new smear-positive
      registration rate will have become 23.5/100 000 (95% CI: 10.0 - 37.0) and the
      national new smear-positive case detection rate will have reached 51.8% (95% CI:
      22.0 - 81.5). CONCLUSION: Our research finding revealed that not only the
      expansion of DOTS could promote the rate of TB case detection but the quality of
      DOTS also played an important role in the TB control program. In order to reach
      the target of 70% case detection rate in 2005, programs as accelerating the DOTS
      expansion to increase the DOTS coverage and improving the quality of DOTS as well
      as other control measures need to be strengthened.

PMID- 15555383
TI  - [Health seeking behavior and access to health care among patients with chronic
      cough diagnosed by county general hospitals in northern parts of Jiangsu
      province].
AB  - OBJECTIVE: To analyze the impact of socioeconomic and demographic factors on
      health-seeking behavior among patients with long-term chronic cough. METHODS: 310
      patients with chronic cough, identified in two county general hospitals from the
      study sites were involved in a cross-sectional study. Questionnaire and personal
      interview were used for data collection. Binary logistic regression, Kaplan-Meier
      method and Cox analysis were applied in multivariate analysis to identify and
      quantify the impact of individual factors regarding the delay of reaching primary
      health care provider and the choice of health facility selection. RESULTS: Delay
      caused by patients themselves showed a difference between the counties with or
      without the programes. Occupation and medical insurance were associated with
      patients' health-seeking behavior. Patients under 18 years old had an earlier
      chance to access the health facility (RR = 1.90, 95% CI: 1.27 - 2.84), and
      choosing the general hospital as their first preference when seeking healthcare
      (RR = 2.06, 95% CI: 1.12 - 3.80). Patients with medical insurance were more
      likely to seek health care service in the general hospitals (RR = 1.64, 95% CI:
      1.35 - 2.10). Only 2.5% of the patients with cough longer than two weeks had
      received sputum smear tests in the general hospitals. CONCLUSION: Occupation,
      medical insurance had great importance to the health seeking behaviors of
      patients with chronic cough which had not been viewed as an 'on-the-alert'
      symptom to be included in the tuberculosis control programs at the general
      hospitals either in the Programmed or Non-programmed counties in Jiangsu
      province.

PMID- 15555384
TI  - [The impact of geriatric tuberculosis patients on the tuberculosis control
      strategy in China].
AB  - OBJECTIVE: To study the current status of geriatric tuberculosis (TB) and its
      impact on TB control program under the directly observed treatment short-course
      (DOTS) strategy in China. METHODS: Using the prevalence information regarding the
      epidemiology of geriatric TB from the National Random Survey in 2000, a case
      control study was carried out to analyze the case detection, treatment and
      management of geriatric TB patients between DOTS area and non-DOTS area. RESULTS:
      The prevalence of sputum smear positive (SS+) in the age group of 65 or above was
      440/100 000 which was 3.6 times of the average prevalence of SS+ of all age
      groups. Geriatric SS+ patients took up 28.8% of all the TB patients in 13
      provinces with implementation of DOTS and 28.9% in 15 provinces without. The
      population of TB case in the age group 65 or above occupied 11.4% of all the
      newly registered SS+ case in 13 DOTS provinces from 1992 to 2000. CONCLUSION: The
      prevalence of geriatric SS+ was high. In both DOTS and non-DOTS areas, the
      proportion of geriatric SS+ was high but the registration rate of new SS+ was low
      among all the age groups. Both high prevalence and low case detection rate of
      geriatric TB became main issues to be under concern in the TB control strategy in
      China.

PMID- 15555385
TI  - [Logistic analysis on risk factors related to smear positive pulmonary
      tuberculosis].
AB  - OBJECTIVE: To explore the risk factors on relapsing tuberculosis related to smear
      positive pulmonary tuberculosis which had been cured for five years. METHODS:
      Patients with smear positive pulmonary tuberculosis registered in 1995 from ten
      countries in Hubei province were studied and logistic regression was used for
      data analysis. RESULTS: The 5-year relapse rate of smear positive pulmonary
      tuberculosis was 3.85 percent. Risk factors related to relapse would include
      being non-modeled county, negative smear after treated for three months, the
      class of retreatment, management of non-DOTS, method of chemotherapy and patients
      that did not get treated by the tuberculosis institute, with odds ratios of 0.15,
      4.62, 3.68, 5.88 and 6.47, respectively. CONCLUSION: Effect standard, regulation
      DOTS and the centralized management measure might have had effects on decreasing
      the relapse rate.

PMID- 15555386
TI  - [Systematic assessment on the improvement of tuberculosis case detection through
      general hospital-based tuberculosis patients transferring system in China].
AB  - OBJECTIVE: To evaluate the reporting and transferring system for tuberculosis
      (TB) patients carried out by city General Hospitals & township clinics in the
      last 10 years in China. METHODS: Systematic review and Meta-analysis were carried
      out. RESULTS: After 5 years of follow-up on the outcomes of intervention, it was
      found that both the rates of newly registered smear positivity and the new case
      registration on smear positivity had significantly been increasing during the
      last five years and the scale of increase was growing annually during the first
      three years. However, the scale of increase started to decline on the fourth
      year. The combined RR on the failure of transfer rate was 0.36 (95% CI: 0.25 -
      0.53). CONCLUSION: The integrated outcomes showed that the ongoing reporting and
      transferring system in general hospital was benefit for TB case detection.

PMID- 15555387
TI  - [A study on the association between tea consumption and stroke].
AB  - OBJECTIVE: The aim of the study was to investigate the association between tea
      consumption and stroke. METHODS: A cross sectional study was conducted in autumn,
      1998. The subjects were from 12 provinces in China. 15 groups of populations were
      selected by cluster randomized sampling and each group had about 1000 persons,
      aged from 35 to 60 years old. 14 212 subjects had complete data for analysis.
      Data regarding tea drinking would include drinking status, dose and type of teas.
      Logistic regression was used to analyze the association between tea consumption
      and stroke. RESULTS: There was a strong inverse correlation between tea drinking
      and stroke after adjusting other risk factors of stroke (P < 0.05). The odds
      ratio (OR) of stroke was 0.60 [95% confidence interval (CI): 0.42 - 0.85] for
      subjects who drank tea compared to those who did not. Increased amount of tea
      consumption per month was associated with decreased stroke prevalence. The
      association for tea consumption over 150 gram per month and stroke was
      statistically significant (P < 0.05) with an OR value of 0.56 (95% CI: 0.36 -
      0.89). Analytical results indicated that the OR value was 0.24 (95% CI: 0.06 -
      1.01) for black tea and other tea (P = 0.05). The OR value was 0.35 (95% CI: 0.18
      - 0.72) for green tea (P < 0.01), and 0.75 (95% CI: 0.51 - 1.11) for jasmine tea
      (P > 0.05). CONCLUSION: Tea drinking was independently associated with prevalence
      of stroke which might play a role in the prevention of the disease.

PMID- 15555388
TI  - [Etiological study on an outbreak of acute respiratory infection in children in
      Beijing].
AB  - OBJECTIVE: An outbreak of acute respiratory infections in children occurred in
      Beijing from November to December, 2002. To investigate the etiological agents of
      affected children who were in day care centers and primary schools. METHODS:
      Throat swab specimens were collected from one primary school children with acute
      respiratory infections visiting one outpatient department. After centrifuging,
      supernatant from the specimens were inoculated into MDCK and Hep-2 cells for
      virus isolation and pallets for viral antigen detection and using indirect
      immunofluorescent assay on common respiratory viruses. Nested polymerase chain
      reaction was used at the same time for detection of respiratory viruses and
      Mycoplasma pneumoniae (Mp). RESULTS: A total number of 80 specimens were
      collected during the outbreak. Among them influenza B virus were detected from 18
      specimens, with a positive rate of 22.5% (18/80) while Mp were detected from 13
      specimens, with a positive rate of 16.3% (13/80). Influenza A3 were also detected
      from 2 patients (2.5%, 2/80). However, influenza A1, RSV, adenovirus and
      parainfluenza viruses were not found from these specimens. Influenza B virus and
      Mp were detected simultaneity in two specimens and influenza A3 virus and Mp were
      detected in one specimen. CONCLUSION: The outbreak of acute respiratory infection
      in children during the period of investigation was caused by both influenza B
      virus and Mp.

PMID- 15555389
TI  - [Study on the risk factors related to severe acute respiratory syndrome among
      close contactors in Beijing].
AB  - OBJECTIVE: To understand the risk factors on severe acute respiratory syndrome
      (SARS) among their contacts and to develop effective strategy for its control.
      METHODS: Available epidemiological data of SARS cases and close contacts were
      reviewed and analyzed by SPSS. RESULTS: Out of the 2195 close contacts, 138
      (6.3%) were diagnosed as SARS. Among colleagues and classmates of SARS patients,
      the infection rate was 0.36% versus 31.71% in contacts among families and
      hospitals, 0.77% in schools. No one was infected among 459 close contacts to SARS
      in the working unit. CONCLUSIONS: Among close contacts, factors that facilitating
      transmission would include: time, extent, frequency and place of contact to the
      patients, as well as factors related to close contacts as way, time of isolation
      and age. One of the epidemiological characteristics was that SARS were as
      clustered in the family among those close contacts. It is important to control
      the spread of SARS through supervision on the close contacts to patients.

PMID- 15555390
TI  - [Analysis on 2071 cases excluded from severe acute respiratory syndrome in
      Beijing].
AB  - OBJECTIVE: To examine the characteristics of cases excluded from severe acute
      respiratory syndrome (SARS) and the reasons for exclusion. METHODS: 2071 probable
      or suspected cases excluded from SARS between March and June, 2003 were analyzed.
      RESULTS: Two-thirds of the excluded cases were males. Construction workers,
      students and retired people ranked top three in all the occupation categories.
      Three peaks appeared in the dates of exclusion, and the most obvious one was from
      June 7 to June 13. There were two peaks in the distribution of time period from
      onset to exclusion, one was six to ten days and the other was forty-eight to
      fifty-two days after onset. Patients with history of close contact were more
      likely to be excluded within fifty days after onset than those without close
      history of contact. Pneumonia, common cold and lung infection were the leading
      causes for correction in the 1211 excluded cases. CONCLUSION: Study on the
      diagnosis and differential diagnosis should be emphasized.

PMID- 15555391
TI  - [A cross-sectional study on injuries in residents from the countryside of Huanghe
      Delta rural areas].
AB  - OBJECTIVE: To study the incidence of injuries among residents living in the
      countryside of Huanghe delta area. METHODS: A household questionnaire survey was
      conducted to 15 276 residents in 20 villages of Dongying municipality of Shandong
      province with a stratified-cluster sampling on their injuries from March 1, 2002
      to February 28, 2003. Data were analyzed with Excel 2000 and SPSS 11.0 software.
      RESULTS: The crude incidence of injuries was 5.90% in total, and the standardized
      incidence was 5.93%. It was higher in men (7.79%) than in women (4.03%). There
      were 19 deaths with 20 cripples. The standardized death rate was 122.56 per 100
      000 with leading causes of injuries was blunt or by sharp articles (24.61%),
      traffic accident (24.17%), falls (22.62%) and animal bites (13.08%). Peak
      incidence of age group was high in 25 - 54 age group and 0 - 4 age group (>
      6.0%). 267 cases (29.60%) inpatients had had about 15.89 days hospitalization for
      each case. Rest of each case with injury had 19.20 days of rest. Direct economic
      loss for treatment would cost 904.85 RMB Yuan and 10.15 days with care takers and
      221.88 RMB for other cost. The potential years of life lost was 24 years, the
      working years of life lost was 19.6 year, the valued years of life lost was 8.7
      year, and the standardized period expected years of life lost was 31.73 year.
      CONCLUSION: Injury was common and frequently occurred among residents in the
      countryside of rural Huanghe delta areas, that seriously endangered the health
      care systems and burden on families.

PMID- 15555392
TI  - [Study on the cost of expanded programme on immunization in areas with different
      economic levels].
AB  - OBJECTIVE: The expanded programme on immunization (EPI) is an important part of
      the social commonwealth projects providing health care service by the government,
      which benefits communities. Government has the responsibility for EPI's financing
      which should be covered by the national budget. It is essential that the cost of
      EPI service be scientifically estimated to provide propriety information for
      policy makers. METHODS: This study, using the cost accounting theory of health
      economics, to calculate EPI service cost at different levels. 3 provinces, 3
      prefectures, 9 counties, 18 towns and 12 villages were selected from three
      provinces Guizhou, Heilongjiang and Zhejiang from the western, central and
      eastern regions of the country. RESULTS: The average costs for one EPI-targeted
      child in Guizhou, Heilongjiang and Zhejiang, were 15.68 Yuan, 29.00 Yuan and
      31.09 Yuan, and the costs for one dose were 10.99 Yuan, 18.64 Yuan and 16.51
      Yuan, respectively. The costs for complete immunization program for one child
      were 131.88 Yuan, 242.32 Yuan and 280.67 Yuan, respectively. The main factors
      affecting the cost would include the average personnel cost (salary and benefit
      cost) by different economic levels of areas, the number of EPI items developed,
      and the number of total doses for one child. CONCLUSION: (1) Obvious differences
      were found between different areas. (2) The proportion of the cost was not
      reasonably set because of the shortage of input. (3) Guideline for different
      areas to compensate the working item cost according to the number of the items
      should be formulated.

PMID- 15555393
TI  - [A community-based case-control study on risk factors of hyperuricemia among
      residents in the community].
AB  - OBJECTIVE: To investigate the risk factors of hyperuricemia among residents aged
      >/= 20 years. METHODS: A community based case-control study was conducted in 286
      patients with 858 controls without hyperuricemia. Available data were analyzed by
      mono-factorial and multi-factorial logistic regression methods using SPSS 10.0
      software. RESULTS: 17 factors related to exposure were identified for
      hyperuricemia the mono-factorial analysis when; five factors were selected
      through multiple factoral logistic regression model at P = 0.05 level. The risk
      factors on hyperuricemia were: hypertriglyceridemia (OR = 3.069), alcohol
      consumption (OR = 2.032), obesity (OR = 1.802), taste of spicy food (OR = 1.877)
      and hyperglycemia (OR = 1.622). CONCLUSION: Hyperuricemia is a disease associated
      with environment and style-life. Changing lifestyle, such as decreasing alcohol
      consumption and adopting proper structure of diet may prevent or decrease the
      chance of getting hyperuricemia and gout.

PMID- 15555394
TI  - [Risk factors associated with reinfection of Schistosoma japonicum].
AB  - OBJECTIVE: To explore the risk factors of Schistosoma japonicum reinfection after
      chemotherapy in a hilly endemic area. METHODS: In a hilly endemic area of S.
      japonica, data on contact to contaminated water and the rates of reinfection
      after mass praziquantel treatment were collected from residents who participated
      in a prospective cohort study on S. japonica. An unconditional logistic
      regression analysis was performed to identify the risk factors associated with
      the reinfection of S. japonicum. RESULTS: Logistic regression analysis data
      showed that three factors were associated with S. japonicum reinfection: eggs per
      gram stool (EPG) prior to chemotherapy (OR = 2.066, 95% CI: 1.173 - 3.639),
      gender (OR = 4.260, 95% CI: 1.275 - 14.235) and average degree of exposure (Index
      B) from April to October (OR = 1.138, 95% CI: 1.045 - 1.240). Interaction between
      gender and average exposure Index B from April to October was identified (OR =
      0.875, 95% CI: 0.817 - 0.982). CONCLUSION: Eggs per gram stool (EPG) prior to
      chemotherapy, level of exposure to infected water and gender were risk factors
      for reinfection with S. japonicum after chemotherapy. In addition, there appeared
      an antagonism between gender and level of exposure to infected water.

PMID- 15555395
TI  - [Dynamics of peripheral blood B lymphocytes and natural killer cells in patients
      with severe acute respiratory syndrome].
AB  - OBJECTIVE: To study the dynamics of peripheral blood B lymphocytes and natural
      killer (NK) cells in patients with severe acute respiratory syndrome (SARS).
      METHODS: The absolute numbers of peripheral blood B lymphocytes and NK cells in
      602 serial samples from 240 patients with SARS were counted, using flow
      cytometry, and compared with that of normal population. RESULTS: The absolute
      numbers of peripheral blood B lymphocytes and NK cells in SARS patients were
      significantly lower than that of the normal population (P < 0.001) and were much
      lower in SARS patients with severe or extremely severe types, as compared with
      that of moderate or mild type cases (P < 0.001). The amount of B lymphocytes in
      recovery SARS patients increased at the 2nd week after onset, and gradually
      becoming normal at the 5th week of the disease onset. The number of NK cells was
      in the low level at onset, and keep decreasing at the 2nd week. However, it was
      increasing with the recovery of the disease, but did not reach to normal level at
      the 5th week after onset. CONCLUSION: The absolute numbers of peripheral blood B
      lymphocytes and NK cells were associated with the severity of the disease, and
      detection of these two kinds of cells was useful for predicting the prognosis of
      SARS.

PMID- 15555396
TI  - [Amplification and typing of Sta56 gene of Orientia tsutsugamushi from Shandong
      province].
AB  - OBJECTIVE: To clarify the gene type of Orientia tsutsugamushi (Ot) from Shandong
      province. METHODS: Nested-polymerase chain reaction (nPCR) was used to identify
      the gene type of 23 isolated Ot strains, 2 pools of homogenized leptotrombidium
      (L.) scutellare, 10 blood specimens of scrub typhus patients, and at the same
      time to compare with the international reference strains Gilliam, Karp, Kato.
      Sequencing analysis of the Sta56 gene was also used to further identify the
      precise gene types. RESULTS: Of the 35 samples, 33 had the same products in the
      amplification of template Ot-DNA. They all belonged to Kawasaki strains endemic
      in Japan while 2 (FXS4 and LHGM2 strain) belonged to Karp strains. The Sta56 gene
      sequence homologies to Japan Kawasaki strain of the 2 representative strains (B
      16 and FXS2 strain) of the 33 samples were 94.22%, 95.21% respectively, but they
      were less than 75.87% to other prototype strains; The homologies to Karp strain
      of FXS4 and LHGM2 strain were 83.03%, 96.45% respectively. B-16 and FXS2 strain
      were designated as of types strain Japan Kawasaki, FXS4 and LHGM2 as Karp strain.
      CONCLUSION: The results indicated that the dominant Ot strains in Shandong
      Province were similar to Kawasaki strains, but Karp strains also existed.

PMID- 15555397
TI  - [Genetic polymorphisms in X-ray repair cross-complementing gene 1 and
      susceptibility to papillary thyroid carcinoma].
AB  - OBJECTIVE: To study the association of polymorphisms in the X-ray repair cross
      complementing gene 1 (XRCC1) and papillary thyroid carcinoma (PTC). METHODS: A
      hospital based, matched case-control study was carried out. The polymorphisms in
      XRCC1 for 105 pairs of cases with PTC and controls were identified by PCR-RFLP.
      RESULTS: The frequencies of Arg/Arg, Arg/Trp and Trp/Trp genotypes at XRCC1
      Arg194Trp site were 47.6%, 49.5% and 2.9% among cases compared to 45.7%, 48.6%
      and 5.7% among controls. There was no statistically significant difference
      between the two groups (chi(2) = 1.07, P = 0.59). The frequencies of Arg/Arg,
      Arg/Gln and Gln/Gln genotypes at XRCC1 Arg399Gln site were 46.7%, 41.9% and 11.4%
      among cases, while 54.2%, 42.9% and 2.9% among controls respectively. There was
      statistically significant difference between the two groups (chi(2) = 6.40, P =
      0.04). Individuals with Gln/Gln genotype had a 3.65-fold increased risk of
      developing PTC compared to Arg/Arg genotype (OR = 4.65, 95% CI: 1.24 - 17.45).
      The multivariate conditional logistic regression analysis showed that the XRCC1
      Arg399Gln polymorphism, negative life events and X-irradiation history were
      associated with PTC, with odds ratios of 2.71 (95% CI: 1.22 - 6.05), 5.34 (95%
      CI: 1.40 - 20.38) and 0.38 (95% CI: 0.12 - 0.72) respectively. However, XRCC1
      Arg194Trp polymorphism, drinking tea, fruit and economic levels did not show
      statistically significant associations with PTC. CONCLUSION: The Gln/Gln genotype
      at XRCC1 Arg399Gln site and negative life events significantly increased while X
      irradiation history decreased the risk of developing PTC.

PMID- 15555398
TI  - [Risk factors for allergic asthma in a case-control study among adults].
AB  - OBJECTIVE: To investigate the risk factors allergic asthma in adult as well as
      the indoor environmental risk factors. METHODS: Case-control study was used to
      collect the information from 102 cases of adults' allergic asthma and 394
      controls. The information included general social demographic characteristics,
      disease history, smoking history, occupation, indoor environmental situation and
      genetic history of the families. RESULTS: The case group had higher proportion of
      the history on occupational dust exposure than the control group (P < 0.05, OR =
      1.78) with statistical significance. Poorer housing condition were more likely to
      cause adult allergic asthma or onset, with an odds ratio of 3.24. The results
      also showed that there was a correlation between the frequency of "quilt
      solarization" and adult allergic asthma (P < 0.10, OR = 1.53). We also found that
      the frequency of having woody floor in the living room of the patients cases was
      higher than that in the controls (P < 0.01, OR = 2.33) so as the degree of indoor
      cooking-oil fume contamination (P < 0.01, OR = 2.52). The statistical significant
      correlation was also found between the adult allergic asthma and the history of
      asthma or chronic bronchitis of their parents (P < 0.01, OR = 2.32). CONCLUSIONS:
      The study showed that the indoor environmental risk factors as poor housing
      condition, fewer frequency of solarization for quilts, woody floor in the living
      room as well as indoor cooking-oil fume contamination were the possible risk
      factors related to adult allergic asthma. Occupational dust exposure and the
      family genetic history were also the possible risk factors. The study indicated
      that adult allergic asthma was a multi-factorial complex disease and the
      interaction of environmental and genetic risk factors played an important role in
      the onset of this disease.

PMID- 15555399
TI  - [Profile on circadian blood pressure and the influencing factors in essential
      hypertensive patients after treatment].
AB  - OBJECTIVE: To explore the circadian blood pressure (BP) profile and its
      influencing factors in essential hypertensive patients after treatment. METHODS:
      Cross-sectional surveillance was carried out in essential hypertensive subjects
      after treatment whose clinic blood pressure had been under control as 140/90 mm
      Hg (1 mm Hg = 0.133 kPa) for at least one month. All patients underwent a twenty
      four-hour ambulatory blood pressure monitoring device (spacelabs 90207). The
      nocturnal fall of blood pressure (BP) was calculated from (daytime mean BP-night
      time mean BP)/daytime BP, while 'daytime' values were recorded between 6 h and 22
      h and 'night-time' values between 22 h and 6 h. Non-dippers were defined as those
      whose nocturnal decrease in mean systolic BP and/or mean diastolic BP was < 10%
      of the daytime BP. Binary logistic regression analysis was used to evaluate the
      correlation between circadian blood pressure profile and factors as gender, age,
      height, body mass index (BMI), family history of premature cardiovascular
      disease, women under age 65 or men under age 55, smoking habits, grade of
      hypertension, and strategy of antihypertensive drugs. RESULTS: 208 treated
      essential hypertensive patients were enrolled in the study. 79 individuals were
      dippers and 129 were non-dippers. Data from logistic regression analysis showed
      that four factors as age, premature family history of cardiovascular disease,
      overweight or obesity, and strategy of antihypertensive drugs were significantly
      influencing the circadian blood pressure profile in treated hypertensive
      patients. The incidence of non-dippers in patients of 70 years of age or older
      and those between 60 and 69 were 3.3 and 2.3 times of those with less than 60 (P
      = 0.009 and 0.031, respectively). The prevalence of non-dippers in patients with
      a premature family history of cardiovascular disease was 3.7 times greater than
      those in subjects without a premature history of cardiovascular disease (P =
      0.029). Similarly, the incidence of non-dippers in patients of overweight (24 </=
      BMI < 28) and obesity (BMI >/= 28) were 3.0 and 4.8 times of those in subjects of
      normal weight (P = 0.003 and 0.009, respectively). Compared with patients treated
      with long-acting calcium channel blockers (CCBs), patients treated with
      angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor
      blockers (ARBs) alone had less prevalence of nondippers (OR = 0.139, P = 0.010).
      Patients treated with joint antihypertensive scheme including ACE inhibitors or
      ARBs(but not including diuretics) had the tendency of lower incidence of abnormal
      circadian blood pressure rhythm (OR = 0.453, P = 0.118). Patients treated with
      joint antihypertensive scheme including diuretics (not including ACE inhibitors
      or ARBs) and with joint antihypertensive strategy including diuretics and ACE
      inhibitors or ARBs had lower incidence of nondippers (OR = 0.378 and 0.273,
      respectively; P = 0.030 and 0.011, respectively). CONCLUSIONS: Approximately 2/3
      treated essential hypertensive patients had a non-dipper blood pressure profile.
      Age, premature family history of cardiovascular disease, overweight/obesity, and
      antihypertensive drugs strategy were correlated with circadian blood pressure
      profile. Compared with long-acting CCBs, diuretics, ACE inhibitors or ARBs might
      be helpful in keeping the circadian blood pressure rhythm at normal range.

PMID- 15555400
TI  - [Study on the application of artificial neural network in analysing the risk
      factors of diabetes mellitus].
AB  - OBJECTIVE: To study the use of neural network in determining the risk factors of
      diseases. METHODS: With back-propagation neural network (BP network) as fitting
      model based upon data gathered from an epidemiological survey on diabetes
      mellitus and under the network structure of 22-6-1, the mean impact value (MIV)
      for each input variables and sequencing the factors according to their absolute
      MIVs were calculated. The results from BP network with multiple logistic
      regression analysis and log-linear model for united actions between factors were
      compared with optimizing Levenberg-Marquardt algorithm. RESULTS: By BP network
      analysis, the sequence of importance for the risk factors of diabetes mellitus
      became: faster pulse, diabetes mellitus family history, living longer in the
      investigated area, with medical record of nephropathy, having higher ratio for
      waist-to-hip, being male, with medical records of diseases as
      hyperlipoproteinmia, coronary heart disease, hypertension, high diastolic
      pressure, higher income, do no drink alcohol, age, higher systolic pressure, less
      educated, body mass index, with medical records of other diseases, physical
      exercise related to jobs smoking, occupation, with medical record for
      cerebrovascular disease, with medical record for liver disease etc. However, only
      7 factors were statistically significant in multiple logistic regression
      analysis. The sequence of their importance appeared as: pulse, diabetes mellitus
      family history, the medical record of nephropathy, waist-to-hip ratio, the
      medical record of hypertension, work-place related exercise and age. The
      sequences of importance were almost the same between the two while the difference
      could partly be explained by the interaction among risk factors through log
      linear model. CONCLUSION: Neural network could be used to analyze the risk
      factors of diseases and could assimilate more complicated relationships (main
      effects and interactions) between inputs and outputs, better than using the
      traditional methods.

PMID- 15555401
TI  - [Advances in the study of remote sensing for monitoring and predicting the
      epidemiologic factors of schistosomiasis].

PMID- 15555402
TI  - [Maternal mortality and main cause of death in Jiaxing Area, Zhejiang Province
      and Suzhou Area, Jiangsu Province 1980--1999].

PMID- 15555403
TI  - [Predictive value of pulse pressure in cardiovascular diseases].

PMID- 15555404
TI  - [Relation between iodine intake and thyroid goiter].

PMID- 15555406
TI  - [Epidemiologic characters of diabetic mellitus in urban and rural community in
      2003 in Hangzhou City].

PMID- 15555407
TI  - [Epidemiology of communicable diseases in Huangpu District, Shanghai City, 1996-
      2002].

PMID- 15555408
TI  - [Polymorphism of NAD(P)H dehydrogenase (quinone) 1 (NQO1) C 609 T and risk of
      esophageal neoplasm].

PMID- 15555409
TI  - [Discovery of new strain of E coli O157: H7 with K antigen].

PMID- 15555410
TI  - [Pseudomonas aeruginosa lung infections of senior patients in intensive care
      unit].

PMID- 15555411
TI  - [Risk factors of Hypertension in rural population in Zhangwu Count, Liaoning
      Province].

PMID- 15555412
TI  - [Comparative study of immunogenicity and safety of domestic influenza vaccines].

PMID- 15555413
TI  - [Current status of epidemiology of rabies and its immunologic prevention].

PMID- 15555414
TI  - A modified Ce/Mg-BCIP-NBT formazan/indigoblue technique for demonstration of non
      specific alkaline phosphatase activity.
AB  - The wide ranged structurally variability of formazans and their accessibility for
      auxiliary additives as redoxmediators or metals provide an easy tunable
      chromogenic visualization technique. We present here an improved nitro blue
      tetrazolium (NBT) 5-bromo-4-chloro-3-indolyl phosphate (BCIP) method which is
      superior to the classical McGadey's procedure regarding proper precipitation and
      localization as well as sensitivity. Different metal additives as well as the
      overall reaction course modifying additives (redox mediators, chelating
      additives, buffer) were optimized.

PMID- 15555415
TI  - Asymmetry alters immune-partner relationship.
AB  - Ambiguity in the mutual manipulation between the immune system, more
      appropriately termed integrated defense system, on the one hand and microbes and
      incipient tumors on the other, is to be taken into account. Such ambiguity may
      also apply to autoimmune infighting. Here we consider the association of its
      increased incidence with modern ways of living. Indifference about fate implies
      that longstanding, evolutionary regulated, immune/tissue relationships are no
      impediment for asymmetric estrangement promoted by ongoing globalization.

PMID- 15555416
TI  - In vitro H2O2 stress and patterns of mitochondrial damage in the NCTC 2544
      continuous cell line--a morphologic and morphometric study.
AB  - The morpho-functional and energy condition of NCTC 2544 cells exposed for 1 hr to
      a high concentration of H2O2 (500 microM) was studied at 4 and 24 hr to
      investigate the short- and medium-term biomolecular mechanisms affecting
      energetic mitochondrial capability. Morphometric data obtained from
      ultrastructural investigations clearly showed significant modifications of the
      different mitochondrial parameters--numerical density (Nv), volume density (Vv)
      and Vv/Nv ratio, in interkinetic, apoptotic and mitotic cells after H2O2 exposure
      (from 4 to 24 hr). These results were confirmed by the detection at 24 hr of
      mitochondrial cytochrome c release in the cytosol, indicating impairment in
      mitochondrial membrane permeability. Data supporting these observations were
      obtained from the MTT test which showed reduced cell viability in H2O2 treated
      cultures at 4 hr and an even greater decrement at 24 hr. In conclusion our data
      imply that significant cause-effect relationships exist between the toxicity of
      reactive oxygen species (i.e. 500 microM H2O2) and morpho-structural
      mitochondrial damage in interkinetic, apoptotic and mitotic cells, respectively.
      They support previous results present both in the literature and also in one of
      our earlier papers which show that early nuclear DNA damage could initiate
      mitochondrial or intrinsic apoptotic pathway after H2O2 exposure.

PMID- 15555417
TI  - Separation of trophoblastic and vascular cell lineages and vascular maturation in
      early human placental development.
AB  - The trophoblast and vascular cell lineages have been studied by
      immunohistochemistry at 6 and 12-14 weeks of pregnancy. Perivillous and
      extravillous cytotrophoblasts were specifically stained by anti-cytokeratin 7
      whereas endothelial cells were labelled by anti-CD34 at these two stages of
      pregnancy. Perivillous and extravillous cytotrophoblasts together with
      erythroblasts showed mitotic figures and anti-Ki67 positive nuclei at the 6th
      week. In the perivillous cytotrophoblast, the number of Ki67 positive nuclei
      decreased by 12-14 weeks and the staining was limited to the proximal
      extravillous trophoblast of cell islands. Some endothelial and perivascular cells
      were labelled with anti-Ki67 at 12-14 weeks. Erythroblasts did not stain at all
      at this stage. Endothelial cells bound lectin UEA1 and vessels exhibited a
      fluorescent signal after anti-myosin staining at 12-14 weeks. These data showed
      that the cytotrophoblast and endothelial cell lineages are not related from 6 to
      12-14 weeks of pregnancy. Because mitotic figures or anti-Ki67 staining were not
      observed in endothelium or perivascular cells at the 6th week, it seems likely
      that the endothelial cells committed to vasculogenesis derived from stromal
      cells. By 12-14 weeks, endothelial cells had nearly achieved their maturation by
      acquiring 1-fucosyl-binding sites revealed by UEA1-lectin binding and insuring
      their own renewal by mitosis. The maturation of perivascular cells at 12-14 weeks
      was shown by the anti-sm-myosin staining. We conclude that placental
      vasculogenesis involves mesenchymal cells rather than trophoblast. The
      differenciation of vessels organizing from random plexi to a vascular
      arborescence may involve paracrine regulatory loops with the trophoblast.

PMID- 15555418
TI  - Regulatory volume increase in nematocytes isolated from acontia of Aiptasia
      diaphana (Cnidaria, Anthozoa).
AB  - Nematocytes, Cnidarians stinging cells used primarily in capturing prey or in
      turning away predators, can regulate their volume under 35% hyposmotic shock
      showing regulatory volume decrease (RVD). In this study, for the first time, we
      investigate the capability of nematocytes to regulate their volume under
      hypertonic conditions, through regulatory volume increase (RVI). The experiments
      were carried out in acontial nematocytes of Aiptasia diaphana (Cnidaria:
      Anthozoa) isolated by the chemical method of applying 605 mM SCN-. Channel
      inhibitors, as amiloride, Gd3+, NPPB, DIDS, bumetanide and ion substitution have
      been employed to assess the role of ions in such volume regulation mechanisms.
      Our results suggest that nematocytes are able to perform RVI. The regulatory
      volume recovery process after hypertonic stimulation involves Na+ conductance and
      Na+/K+/2Cl- cotransport but not Cl- conductive pathways. Further studies will be
      necessary to better define such mechanisms and RVI control signalling, taking
      into account that the nematocyte is known to be a very primitive eukaryotic cell.

PMID- 15555419
TI  - Lead induced oxidative stress and its recovery following co-administration of
      melatonin or N-acetylcysteine during chelation with succimer in male rats.
AB  - Lead is a ubiquitous element in the environment causing oxidative burst in the
      exposed individuals leading to tissue damage. Antioxidants have long been known
      to reduce the free radical-mediated oxidative stress while, thiol chelators have
      been used to treat arsenic toxicity. The therapeutic efficacy of melatonin or N
      acetylcysteine (NAC) was studied in the present study, both individually and in
      combination with a potent thiol-chelating agent, meso 2,3-dimercaptosuccinic acid
      (DMSA), in reducing lead concentration in blood and other soft tissues. Their
      ability to restore altered haematopoietic, hepatic and other biochemical
      variables indicative of tissue oxidative stress in male rats was also
      investigated. Administration of melatonin and NAC individually, provided
      significant protection to lead induced disturbed antioxidant defense that may
      significantly compromise normal cellular function. Administration of melatonin
      and NAC also provided a significant protection to thiobarbituric acid reactive
      substances (TBARS) levels, reduced glutathione (GSH) and oxidized glutathione
      (GSSG) contents in tissues, suggesting their ability to act as a free radical
      scavenger and in protecting cells against toxic insult. NAC, a thiol containing
      antioxidant, has been used under several clinical conditions with few adverse
      side effects. It has a high toxicity threshold and its wide therapeutic window
      enhances its utility. The antioxidant action of NAC is due to its ability to
      interact with reactive oxygen species (ROS) or its ability to stimulate
      endogenous glutathione (GSH) synthesis. DMSA, on the other hand when given alone,
      provided significant recovery in restoring the altered lead sensitive biochemical
      indices like blood delta-aminolevulinic acid dehydratase (ALAD), urinary delta
      aminolevulinic acid (ALA), beside increasing urinary lead excretion and
      decreasing lead concentration in blood and soft tissues. Interestingly, combined
      treatment of DMSA and NAC provided more pronounced efficacy in restoring altered
      biochemical variables and in reducing body lead burden than monotherapy with
      DMSA. The results thus, suggest the involvement of ROS in lead toxicity and a
      pronounced beneficial role of NAC in therapeutic implications of lead poisoning
      when co-administered with a thiol chelator (DMSA) supporting the hypothesis that
      cellular redox status may be significantly reversed by utilizing a thiol
      containing antioxidant compound. It can be concluded that, combined therapy with
      an antioxidant moiety and a thiol-chelating agent may be a better choice for
      treating plumbism.

PMID- 15555420
TI  - New fluorescent method for the histochemical detection of dipeptidyl peptidase IV
      using glycyl-l-prolyl-2-anthraquinonyl hydrazide as substrate.
AB  - Glycyl-4-prolyl-2-anthraquinonylhydrazide (Gly-Pro-2-AH) was synthesized and used
      as a new fluorogenic substrate for the histochemical detection of dipeptidyl
      peptidase IV activity (DPP IV). The enzymatic hydrolysis liberates 2
      anthraquinonyl hydrazine (2-AH). Further on, the primary reaction product reacts
      with an aromatic aldehyde to give an insoluble hydrazone. The final reaction
      product fluoresces orange-red when exited by green light (lambda(exc)=520-580 nm)
      and marks sites of enzymatic activity by an intensive fluorescence. This
      fluorescent method permits highly sensitive enzyme detection and causes only very
      low background tissue fluorescence. Thus enzyme locations in the capillary bed
      endothelium properly and sensitively stained, which has not been achieved by now.
      The new method is used successfully to demonstrate the enzyme in cryotome tissue
      sections from several rat organs.

PMID- 15555421
TI  - Orientational distribution of collagen fibers in cobra skin.
AB  - The orientation and distribution of collagen fibers were studied in leather
      prepared from cobra skin using both the mechanical method and Osaki's microwave
      method. The degree of preferred collagen-fiber orientation was largest at the
      centre of the dorsum and decreased gradually from the dorsum to the abdomen. The
      collagen fibers were, on average, aligned parallel to the spinal column in the
      dorsum, and tended to be aligned equally in all directions in the abdomen. The
      skin expanded easily in the direction perpendicular to the direction of collagen
      fiber orientation. These results indicate that it is difficult for the skin to
      expand or shrink in the cranial to caudal direction, whereas it is relatively
      easy for the skin to expand around the circumference of the body of the cobra.
      Collagen-fiber orientation therefore seems to be closely related to the
      functional motions of cobra skin during locomotion and when swallowing prey.

PMID- 15555422
TI  - New fluorescent method for the histochemical detection of tripeptidyl peptidase I
      using glycyl-l-prolyl-l-met-2-anthraquinonyl hydrazide as substrate.
AB  - A new substrate for tripeptidyl peptidase I (TPP I; E.C.3.4.14.9)-Gly-L-Pro-L-Met
      2-anthraquinonyl hydrazide (Gly-Pro-Met-2-AH) is synthesized and used for the
      fluorescent histochemical detection of the enzyme. The enzyme liberates low
      soluble 2-anthraquinonylhydrazine, which-couples quickly with 3-nitrobenzaldehyde
      (3-NBA) yielding a highly fluorescent water-insoluble hydrazone--3
      nitrobenzylidene-2-anthraquinonylhydrazone. The latter compound is localized
      precisely at sites of enzymatic activity and marks them with a very bright and
      stable orange-red fluorescence after excitation with conventional monochromatic
      andlaser green light (lambda(exc)=520-580 nm). The new technique is used
      successfully for the visualization of the enzyme in tissue sections of different
      rat organs - and represent the first fluorescent histochemical method for that
      peptidase.

PMID- 15555423
TI  - Autoimmune hepatitides--update 2004.
AB  - This update reports is primarily made to update papers published in 2002 and
      2003. A selection had to be realized since a search of the literature yielded
      more than 1600 journal articles. The prevailing opinion of an international group
      is especially emphasized. Autoimmune hepatitides (AIH)--as the name already
      suggests it--are no disease entity. We prefer to classify them under the terms of
      typical and atypical autoimmune hepatitides. Typical autoimmune hepatitis can be
      subdivided into a type 1 (with antibodies against nuclear material and/or smooth
      muscle) and a type 2 (with antibodies against endoplasmic reticulum). In the case
      of atypical autoimmune hepatitides, the detected autoantibodies would have to be
      stated. The essential feature of an autoimmune hepatitis is the presence of
      various high-titer autoantibodies circulating in serum, especially such of the
      IgG class. Special mention is made of the very rare liver ribosomal antibodies
      (LRA), which are mainly directed against 80S liver ribosomes and point to a so
      called virus-associated autoimmune hepatitis. Also discussed are a genetic
      disposition, which is still speculative in some points, and the existence of so
      called autogenes (physiological, pathological/pathogenic and so-called regulator
      genes). Various noxae, e.g. viruses, might also be "autogenous". Further research
      in the field of the autoimmune hepatitides (and also autoimmunity and autoimmune
      diseases as such) is therefore likely to concentrate on viruses and genes and
      their interrelations.

PMID- 15555424
TI  - Preferential HIV-1 integration sites in macrophages and HIV-associated
      malignancies.
AB  - HIV-infected individuals are at risk for developing certain types of cancers.
      While there are data to show that non-random HIV integration may occur, our goal
      was to identify preferential genomic sites where HIV integration might be
      targeted leading to oncogenesis. Initially, a linker-primer PCR strategy was used
      to identify HIV integration in isolated macrophages. Inverse-PCR was then used to
      analyze specimens from patients diagnosed with HIV-associated malignancies. From
      isolated macrophages, integration near a toll-like receptor on chromosome 4 was
      found. Necropsy tissues from 11 cases were analyzed with 1 tumor specimen found
      to have HIV integrated in chromosome 22q13.2 and within 300 kb of HSCBCIP1 (CAP
      binding protein complex interacting homologue). Tumor-specific primers were then
      used to screen uninvolved tissue from the same patient, which did not amplify the
      site-specific region. This report demonstrates that in both an in vitro system
      and human malignant tissue, specific viral integration can be identified.

PMID- 15555425
TI  - Enhancement of immune responses to hepatitis B vaccine in immunodepressed mice by
      CpG oligodeoxynucleotide.
AB  - AIM: To investigate enhancement of immune response to hepatitis B vaccine in
      immunosuppressed mice by CpG oligodeoxynucleotide (ODN). METHODS: Immunodepressed
      C57BL/6 mice caused by cytoxan were given an injection of either hepatitis B
      vaccine alone or hepatitis B vaccine and CpG ODN into the left tibialis anterior
      muscle, then the mice were given another shot after 2 weeks using the same
      formulation. Blood was collected at 5 weeks after immunization and anti-hepatitis
      B surface antigen IgG and IL-12 levels were measured by ELISA. Spleens of
      immunized mice were observed under microscope. RESULTS: There was a two-fold
      increase in anti-hepatitis B surface antigen IgG level when hepatitis B vaccine
      was mixed with CpG ODN to immunize immunodepressed mice. There was a significant
      increase in IL-12 level when hepatitis B vaccine was mixed with CpG ODN. Under
      optical microscope, there were fewer lymphocytes in immunodepressed mice than in
      normal control group. The proliferation level of spleen lymphocytes in CpG ODN
      group was elevated compared with that of normal control group and nuclei of
      lymphocytes became larger. CONCLUSION: CpG ODN can enhance the immune response to
      hepatitis B vaccine in immunodepressed mice.

PMID- 15555426
TI  - [Construction of C3b(AN42) and OVA(257-264) fusion gene and functional analysis
      of the fusion protein].
AB  - AIM: To explore the role of complement system in the T cell activation. METHODS:
      OVA(257-264) CTL epitope and C3b(AN42) encoding genes were synthesized and cloned
      into expression vector pEGFP-N1. COS-7 cells were transfected with the
      recombinant plasmid pEGFP-N1. The expression of the fusion protein was determined
      by FACS. Twenty-four hours after transfection, cultural supernatants of the
      transfected cells were collected and added to Ana-1 cell culture. Laser confocal
      microscopy was used to detect the binding and presentation of the fusion protein
      by Ana-1 cells. RESULTS: C3b(AN42)-OVA(257-264) fusion protein was expressed in
      COS-7 cells. The fusion protein could bind to Ana-1 cells and OVA(257-264) CTL
      epitope was cross-presented on the surface of Ana-1 cells. CONCLUSION: The
      C3b(AN42)-OVA(257-264) fusion protein can express in COS-7 cells and possesses
      natural biological activity.

PMID- 15555427
TI  - [Soluble PD-1 can augment anti-tumor immunity induced by HSP70-peptide complex in
      tumor-bearing mice].
AB  - AIM: To explore the effect of soluble PD-1 (sPD-1) on the anti-tumor immunity
      induced by HSP70-peptide. METHODS: BALB/c mice were immunized with HSP70-peptide,
      then the cytotoxic activity of splenocytes was detected by MTT colorimetry.
      Expression of PD-1 and its ligand on splenocytes was determined by semi
      quantitative RT-PCR. For some mice, sPD-1 plasmid was injected alone or in
      combination with HSP70-peptide and then the tumor weight and cytotoxic activity
      of splenocytes were measured. RESULTS: sPD-1 alone had anti-tumor effect. HSP70
      peptide complex not only induced tumor-specific cytotoxic T lymphocytes(CTLs),
      but also promoted expression of PD-1 and its ligand. The combination of sPD-1
      with HSP70-peptide complex induced much more stronger anti-tumor effect as
      compared with sPD-1 or HSP70-peptide alone. sPD-1 transfection in mice could
      enhance the cytotoxic activity of splenocytes from immunized mice. CONCLUSION:
      sPD-1 enhanced the anti-tumor efficacy of HSP70-peptide.

PMID- 15555428
TI  - [Cloning of the cDNA of human PD-L1 gene and the expression of its extracellular
      domain in Escherichia coli].
AB  - AIM: To clone human PD-L1 cDNA and construct a prokaryotic expression vector for
      the extracellular domain of PD-L1 gene. METHODS: The human PD-L1 cDNA was cloned
      by RT-PCR from the total RNA of activated human peripheral lymphocytes. The
      prokaryotic expression vector for the extracellular domain of PD-L1 gene was
      constructed and protein expression in E.coli strain BL21(DE3) was determined.
      RESULTS: The full-length gene coding sequence of PD-L1 was cloned and confirmed
      by DNA sequencing. The prokaryotic expression vector for the extracellular domain
      of PD-L1 gene fused with His(6) tag at the C-terminus was then constructed. The
      recombinant protein was expressed in E.coli after IPTG induction and identified
      by Western blot. The expressed product had a relative molecular mass (M(r)) being
      22 000, which was consistent with theoretical value. CONCLUSION: The PD-L1 gene
      was successfully cloned and the extracellular domain of the protein was expressed
      in E.coli, which lays the foundation for further study of the function of PD-L1.

PMID- 15555429
TI  - [Construction and expression of the eukaryotic coexpression plasmid containing
      Ag85B gene of Mycobacterium tuberculosis and IL-12 gene].
AB  - AIM: To construct an eukaryotic coexpression plasmid containing Mycobacterium
      tuberculosis (MTB) Ag85B and IL-12 genes. METHODS: MTB Ag85B gene and IL-12 gene
      were cloned into pBudCE4.1 which has multiple promoters to construct recombinant
      plasmid pBud85B-IL12. The recombinant plasmid was transfected into COS-7 cells
      and the expression of target genes was assessed by RT-PCR and ELISA. RESULTS: The
      expressions of Ag85B and IL-12 could be detected in COS-7 cells. CONCLUSION: The
      recombinant plasmid pBud85B-IL12 was constructed and expressed successfully,
      which lays the foundation for further development of DNA vaccine against
      tuberculosis.

PMID- 15555430
TI  - [Construction and expression of regulatable recombinant adenovirus vector for
      mouse PLP-Ig chimeric protein].
AB  - AIM: To construct a regulatable recombinant adenovirus vector expressing mouse
      proteolipid protein (PLP)-Ig. METHODS: Total RNA was extracted from WT-1
      hybridoma cells to clone Ig heavy chain Fc fragment gene. PCR was carried out to
      link PLP(139-151) gene and signal peptide with Fc fragment gene. pTRE-shuttle
      vector was used to ligate PLP-Ig gene and the backbone of the replication
      incompetent adenoviral vector. After confirming the desired recombinant
      adenovirus by PCR and restriction endonuclease digestion analysis, it was
      packaged and propagated in HEK 293 cells. Tetracycline was used to regulate the
      expression of PLP-Ig, and Western blot was used to detect the gene expression.
      RESULTS: The expression of PLP-Ig was confirmed by Western blot and its
      expression could be regulated by tetracycline. CONCLUSION: The regulatable
      recombinant adenovirus vector for mouse PLP-Ig was constructed and expressed
      successfully, which lays the foundation for further study on gene therapy of EAE
      and induction of immune tolerance.

PMID- 15555431
TI  - [Construction of recombinant plasmid pYTA/Abeta-HBcAg and its expression in
      E.coli].
AB  - AIM: To study the expression of fusion gene Abeta-HBcAg in E.coli and detect the
      immunogenicity of fusion protein Abeta-HBcAg. METHODS: The Abeta-HBcAg fusion
      gene was cut from recombinant plasmid pBV220/Abeta-HBcAg, and was inserted into
      the plasmid pYTA1 to construct recombinant plasmid pYTA/Abeta-HBcAg. The
      recombinant plasmid was transformed into E.coli DH5alpha, and expressed under
      IPTG induction. The expression of the fusion protein Abeta-HBcAg was detected by
      SDS-PAGE. The antigenicity of the fusion protein was detected by ELISA. BALB/c
      mice were immunized intraperitoneally with the fusion protein purified by salting
      out with saturate ammonium sulfate. The titers of anti- Abeta antibodies of the
      immunized mice was evaluated by ELISA. RESULTS: Fusion protein existed in
      supernatant of the bacteria lysate and its expression level was about 7% of the
      total bacteria protein. The fusion protein reacted with both Abeta and HBcAg. The
      highest titer of anti-Abeta antibodies could reach to 1:16 000 after immunization
      for 3 times. CONCLUSION: Recombinant gene Abeta-HBcAg can be expressed in E.coli
      DH5alpha. The expression protein exists in supernatant of the bacteria lysate and
      has good immunogenicity. This study lays the foundation for the experimental
      animal study of AD gene-engineering vaccine.

PMID- 15555432
TI  - [The effects of acute large dose of gamma-irradiation on immune function of
      mice].
AB  - AIM: To observe the effects of large dose of gamma-irradiation on immune function
      of mice. METHODS: 225 cleaning-grad C57 mice, weighing(20+/-2.0) g, were randomly
      divided into 6 groups, and treated with 0, 6, 9, 12, 15 and 20 Gy gamma
      irradiation. At different times after irradiation, lymphocytes were collected and
      lymphocytic apoptosis and T cell subsets were analyzed by TUNEL, May-Grunwald
      Giemsa (MGG) staining and flow cytometry. RESULTS: (1)At early stage(1-14) d
      after radiation, the apoptotic rate of peripheral blood lymphocytes increased
      significantly and 12 Gy radiation resulted in the highest apoptotic rate. The
      number of T lymphocytes and T cell subsets decreased continuously in a dose
      dependent manner. CD8(+) T cells were the most sensitive in T cell subsets to
      irradiation. These results suggested that early severe injury might be one of the
      important features of immune injury caused by acute radiation. (2) One month
      after radiation, the apoptotic rate of lymphocytes began to decrease and T
      lymphocytes and their subsets recovered gradually. However, neither the
      lymphocytic apoptotic rate nor the number of CD3(+) T cells and CD8(+) T cells,
      recovered to normal level, indicating that large dose of radiation had severe
      remote effects on immune function. CONCLUSION: Apoptosis of a large number of
      peripheral blood lymphocytes in early stage after radiation may result in sharp
      reduction of T cell number and late immune function depression.

PMID- 15555433
TI  - [Effect of tryptase inhibitors on histamine release from human colon mast cells].
AB  - AIM: To investigate the effect of tryptase inhibitors (TPIs) on histamine release
      from human colon mast cells. METHODS: Human mast cells were prepared by digestion
      of colon tissue and with collagenase and hyaluronidase, cultured with four kinds
      of TPIs, leupeptin, protamine, TLCK, and lactoferrin for 15 min at 37 degrees
      Celsius respectively. A glass fibre-based fluorometry assay was used to detect
      histamine in mast cell suspension. RESULTS: 200 mmol/L leupeptin and 100 mmol/L
      protamine were able to stimulate histamine release from colon mast cells, while
      TLCK and lactoferrin did not. All TPIs inhibited anti-IgE-induced histamine
      release in a concentration dependent manner, and the inhibitory rates were 48.7%,
      36.7%, 40.2% and 34.1%, respectively. However preincubation of TPIs with mast
      cells for 20 min at 37 degrees Celsius before adding anti-IgE had little effect
      on anti-IgE induced histamine release. All TPIs were able to inhibit calcium
      ionophore (CI)-induced histamine release, and the maximum inhibition rate was
      between 25%-32%. Inhibition on histamine release by leupeptin and TLCK obviously
      enhanced when colon mast cells were preincubated with them for 20 min before
      adding CI. However, under the same condition, protamine failed to inhibit
      histamine release. CONCLUSION: We prove for the first time that TPIs inhibit anti
      IgE-and CI-induced histamine release from human colon mast cells, suggesting that
      it is possible to treat inflammatory bowel disease or other mast cell-related
      diseases by using TPIs.

PMID- 15555434
TI  - [Study on mimotopes of E.coli lipopolysaccharide 2630].
AB  - AIM: To screen mimotopes of E.coli lipopolysaccharide(LPS) 2630 from c7c phage
      display peptide library. METHODS: The LPS mimotopes were screened from c7c phage
      display peptide library by using affinity chromatograph-purified polyclonal
      antibody against E.coli LPS 2630(L2630), and the antigenicity of selected clones
      was identified by ELISA. RESULTS: After 3 rounds of biopanning, 12 out of 20
      phage clones were identified as positive clones which could bind to polyclonal
      anti-L2630 antibody, and 5 of these 12 clones could bind to polyclonal anti
      S.typhi LPS 7261(L7261) antibody. The deduced amino acid sequence analysis showed
      that 8 of 12 clones had the conservative sequence: X-DGLL-XX or X-EDGLL-X.
      CONCLUSION: The peptides displayed on these phage clones can mimic the epitopes
      of L2630, and 5 of these phage clones mimic the common epitopes of L2630 and
      L7261.

PMID- 15555435
TI  - [Study on binding of HBeAg to CD81].
AB  - AIM: To investigate the interaction between HBeAg and CD81. METHODS: The CD81
      gene was amplified by RT-PCR from HepG2 cells. The recombinant expression vector
      pGADT7-CD81 was constructed by routine molecular biological method. The auxotroph
      yeast cells were cotransfected with pGADT7-CD81 and pGBKT7-eAg and plated on
      synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing x-alpha-gal.
      The binding of HBeAg to CD81 was also detected in vitro translation and
      coimmunoprecipitation test. RESULTS: The recombinant expression vector was
      constructed and confirmed by restriction enzyme (EcoR I and BamH I) digestion and
      DNA sequencing analysis. The positive yeast clones could grow and from blue
      colonies on SD/-Trp-Leu-His-Ade/x-alpha-gal medium. The result of
      immunocoprecipitation showed that HBeAg could bind to CD81. CONCLUSION: HBeAg can
      bind to CD81, suggesting that CD81 plays an important role in the pathogenesis of
      HBV.

PMID- 15555436
TI  - [Construction and identification of anti-chymopapain scFv phage display library].
AB  - AIM: To construct phage display library of anti-chymopapain scFv. METHODS: V(H)
      and V(L) gene repertoires were amplified from splenocyte mRNA by RT-PCR and
      joined by a (Gly(4)ser)3 linker to obtain scFv genes. The scFv genes were then
      cloned into phagemid pFAB5C to construct phage display library. Affinity
      selection and ELISA were used to identify specific phage antibody to chymopapain.
      RESULTS: After 4 rounds of panning, high affinity scFv was obtained. CONCLUSION:
      Phage display library of anti-chymopapain scFv was successfully constructed, and
      scFv with binding ability to chymopapain was obtained.

PMID- 15555437
TI  - [Construction and expression of eukaryotic expression vector for intact IgG
      against human keratin].
AB  - AIM: To construct an eukaryotic expression vector containing the gene of anti
      keratin antibody and express it in CHO(dhfr(-)) cells. METHODS: Both the V(L) and
      V(H) genes of an anti-keratin Fab from a phage display library were amplified by
      PCR. Using PCR product as the template, the V(kappa) and V(H) genes with the
      leader sequences (named L(kappa) and L(H) respectively) were amplified by
      overlapping PCR. After digested with endonuclease Xba I/BamH I and Xho I/Hind
      III, L(kappa) and L(H) genes were inserted into pWD digested with Xba I/BamH I
      and Xho I/Hind III, respectively to construct pWDkappaH. After PCR and
      sequencing, the expression plasmid pWDkappaH was transfected into CHO (dhfr(-))
      cells. The culture supernatant of the transfected cells was collected and assayed
      for IgG activity. RESULTS: The eukaryotic expression vector pWDkappaH was
      constructed successfully and expressed in CHO(dhfr(-)) cells. The expression of
      intact IgG against keratin was identified by ELISA and RT-PCR. CONCLUSION: The
      successful expression of intact IgG against keratin lays the foundation for its
      clinical application.

PMID- 15555438
TI  - [Preparation and preliminary application of monoclonal antibody against
      recombinant human erythropoietin].
AB  - AIM: To prepare monoclonal antibody (mAb) against erythropoietin(EPO),
      characterize its biological properties and use it to purify the rhEPO from
      transgenic goat milk. METHODS: A crude rhEPO product was used as the antigen to
      immunize BALB/c mice for preparing mAbs against rhEPO. The mAbs were
      characterized by Western blot and indirect ELISA. Purified mAb 2E6 was coupled
      with pre-activated Sepharose 4B to prepare the immunoaffinity chromatography
      column for purifying the rhEPO from transgenic goat milk. RESULTS: Two hybridoma
      cell lines(1E7 and 2E6)were obtained. mAbs 1E7 and 2E6 were shown to be IgG1 and
      IgG2b respectively, and their light chains were both kappa. Western blot analysis
      confirmed that the two mAbs could bind to rhEPO. The immunoaffinity
      chromatography column could adsorb 70% of rhEPO in purifying the rhEPO from
      transgenic goat milk. CONCLUSION: Two hybridoma cell lines secreting anti-rhEPO
      mAbs were successfully established. The mAb-immunoaffinity chromatography column
      could be used to purify the rhEPO from transgenic goat milk.

PMID- 15555439
TI  - [Preparation and characterization of the monoclonal antibody against HIV-1 p24
      antigen].
AB  - AIM: To establish hybridoma cells secreting monoclonal antibodies (mAbs) against
      HIV-1 p24 antigen and characterize their properties. METHODS: BALB/c mice were
      immunized with purified p24 protein and then the from splenocytes immunized mice
      were fused with Sp2/0 cells. Monoclonal hybridoma cell lines were obtained by
      limiting dilution, HAT and HT-selective culture. The specificity of mAbs was
      identified by Dot blot and indirect ELISA. RESULTS: We had established two
      hybridoma cell lines secreting mAbs against HIV-1 p24 antigen. The titers of two
      mAbs in ascitic fluid were 1 x 10(-5) and 1.7 x 10(4)-1.8 x 10(4) mol/L,
      respectively. Both mAbs belonged to IgG1. Indirect ELISA detection demonstrated
      that both mAbs had no cross-reactivities with other viral antigens, such as
      HBcAg, HCV RNA positive sera and HIVgp41. CONCLUSION: Two hybridoma cell lines
      secreting mAbs against HIV-1 p24 antigen have been established successfully,
      which lays the foundation for detecting HIV-1 p24 antigen.

PMID- 15555440
TI  - [Preparation and characterization of monoclonal antibodies against the
      hemagglutinin of H9 subtype of avian influenza virus].
AB  - AIM: To prepare monoclonal antibodies (mAb) against the hemagglutinin(HA) of H9
      subtype of avian influenza virus (AIV). METHODS: 8 week-old female BALB/c mice
      were immunized with the inactivated vaccine of H9 subtype of AIV. Splenocytes
      from the immunized mice were fused with Sp2/0 myeloma cells, and positive
      hybridoma clones were screened by indirect ELISA and hemagglutination inhibition
      test (HI). The specificity of the mAb was characterized by ELISA, HI test,
      indirect immunofluorescence (IF) staining and Western blot. RESULTS: Three
      hybridoma cell lines named 2H1, 2A3 and 1C8 against HA of AIV H9 were obtained.
      The HI titers of 3 mAbs were 1 x 2(8)-1 x 2(13), and the ELISA titers were 1 x
      10(-7), 1 x 10(-5) and 5 x 10(-6), respectively. The immunoglobulin subclass of
      all 3 mAbs was IgG1. Western blot analysis confirmed that mAb 2H1 could recognize
      HA and reacted to 31 out of 32 isolates of H9 subtype of AIV. CONCLUSION: Three
      mAbs recognizing HA of H9 subtype of AIV were obtained, which may provide an
      useful tool for the antigenic analysis, the serological diagnosis, the
      epidemiological survey and the evaluation of AIV vaccine.

PMID- 15555441
TI  - [Transient expression and characterization of intracellular single chain Fv
      against the nucleocapsid protein of Hantavirus].
AB  - AIM: To transiently express an intracellular single chain Fv of monoclonal
      antibody 1A8 against nucleocapsid protein of Hantavirus and characterize the
      immunological activities of the expressed products. METHODS: COS-7 cells were
      transfected with mammalian expression vector 1A8-scFv-Ckappa/pCI-neo via
      lipofectin. The expressed product was identified by indirect immunofluorescence
      and immunoprecipitation. RESULTS: A diffuse pattern fluorescence was observed in
      less than 1% cytoplasm of transfected COS-7 cells. The binding of intracellular
      antibody fragments to NP antigen was confirmed by immunoprecipitation analysis.
      CONCLUSION: Transiently expressed single chain intrabodies can effectively target
      NP antigen in the cytoplasm. The present study may provide a new approach for
      treatment of Hantavirus.

PMID- 15555442
TI  - [The effect of splenic lymphocytes from oral immune tolerance rats on activity of
      NF-kappaB p65 in glomerular mesangial cells].
AB  - AIM: To explore the effect of splenic lymphocytes from oral immune tolerance rats
      on NF-kappaB p65 activity in glomerular mesangial cells. METHODS: 10 female
      Wistar rats with 6-8 weeks of age were divided randomly into two groups, 5 rats
      for each group. The rats of one group were given through intragastric feeding
      with 2 mL Fx1A antigen to induce oral immune tolerance, and the rats of the other
      group only with PBS (as control group). Two weeks later, the rats were
      sacrificed, and then their spleens were excised and lymphocytes were separated
      routinely for antigen-specific lymphocytes reaction. The culture supernatants of
      splenic lymphocytes from oral immune tolerance rats were prepared. The IL-10
      level in the supernatants was detected by sandwich ELISA. After the cultured
      mesangial cells were stimulated with high dose of insulin, the culture
      supernatants of rat's splenic lymphocytes were added to insulin-treated mesangial
      cells. Twenty-four hours later, the NF-kappaB p65 activity in mesangial cells was
      detected by immunohistochemical staining and sandwich ELISA. RESULTS: As compared
      with control group, the proliferation reaction of splenic lymphocytes from oral
      immune tolerance rats was inhibited obviously, and IL-10 level in splenic
      lymphocyte culture supernatants from the tolerance rats rose markedly (P<0.01).
      NF-kappaB p65 activity induced by insulin in mesangial cells was inhibited by
      culture superatants of splenic lymphocytes from oral immune tolerance rats
      (P<0.05). CONCLUSION: NF-kappaB p65 activity in mesangial cells may be inhibited
      by IL-10 secreted by splenic lymphocytes from the oral immune tolerance rats.

PMID- 15555443
TI  - [NF-kappaB expression in lung tissue of acute lung injury rat model and the
      influence by antioxidant N-acetylcysteine].
AB  - AIM: To observe the NF-kappaB expression in the lung tissue of LPS-induced acute
      lung injury(ALI) rat model and the influence of N-acetylcysteine (NAC) on NF
      kappaB expression. METHODS: The expression of NF-kappaB in lung tissue in ALI rat
      model and the influence of NAC on NF-kappaB expression were detected by
      immunohistochemical (ABC) staining and Western blot. RESULTS: There were a small
      amount of sporadic NF-kappaB cells in airway epithelium and interstitium in
      normal control group. In contrast, nuclear NF-kappaB expression-positive cells
      increased obviously in airway mucosa, lung interestium, alveolar cavity and
      vascular wall of ALI rats. NF-kappaB(+) cells were mainly airway mucosa
      epithelial cells, infiltrating inflammatory cells, alveolar epithelial cells, and
      vascular endothelial cells. The NF-kappaB expression-positive cells in NAC
      therapy group notably decreased compared with ALI group and control
      group(P<0.01). Western blot analysis showed that the expression of NF-kappaB was
      different at various time points, reaching the peak at 3 h and then decreased
      (P<0.01) after LPS induced lung injury. CONCLUSION: In LPS induced acute lung
      injury rat model, the NF-kappaB nuclear expression increased obviously in airway
      mucosa, lung interestium and alveolar cavity. Most cells in lung tissue
      participated in the activation of NF-kappaB. NAC could alleviate inflammation by
      inhibiting activation of NF-kappaB.

PMID- 15555444
TI  - [Effect of human VEGF165 in vitro on proliferation of vascular endothelial
      cells].
AB  - AIM: To observe the effect of human VEGF165 on the proliferation of vascular
      endothelial cells(VECs) in vitro. METHODS: VEGF165 gene was amplified by RT-PCR
      and cloned into eukaryotic expression plasmid pBudCE4.1. The recombinant
      expression plasmid pBudCE4.1/VEGF165 was identified by restriction enzyme(Hind
      III and BamH I) digestion analysis and confirmed by DNA sequencing. The
      pBudCE4.1/VEGF165 was transfected into VECs through lipofection transfection.
      Expression of VEGF165 was detected by Northern blot and immunocytochemical
      staining. The effect of expressed VEGF165 on VEC proliferation was detected by
      flow cytometry. RESULTS: Sequencing analysis revealed that the sequence of cloned
      VEGF165 gene was identical with that in GenBank (accession No.X62568).
      Restrictive enzyme digestion analysis showed that recombinant expression plasmid
      pBudCE4.1/tVEGF165 was constructed successfully. The expression of VEGF165 at
      mRNA and protein levels in the transfected VECs was demonstrated by Northern blot
      and immunocytochemical staining, respectively. The expressed VEGF165 notably
      stimulated the proliferation of VECs. CONCLUSION: pBudCE4.1/VEGF165 is
      successfully constructed and expressed in VECs. Expressed VEGF165 can stimulate
      the VEC proliferation. The present study lays the foundation for using VEGF165
      gene transfection to prevent and treat vascular stenosis in transplanted organ.

PMID- 15555445
TI  - [Expression of human telomerase reverse transcriptase gene in HCC does not depend
      on proliferating cell nuclear antigen and P53].
AB  - AIM: To investigate the expression of human telomerase reverse
      transcriptase(hTERT) gene and its relationship with proliferating cell nuclear
      antigen and P53. METHODS: Immunohistochemical staining was used to detect the
      expressions of hTERT, PCNA and P53 in 42 hepatocellular carcinoma(HCC) tissues.
      The relationship between hTERT expression, pathological characters of HCC and
      PCNA and P53 expression was analyzed. RESULTS: The expression rates of hTERT,
      PCNA and P53 in HCC tissues were 71.4%(30/42),76.2%(32/42) and 73.8%(31/42),
      respectively. hTERT was not expressed in normal liver tissues. The expression
      rates of hTERT gene in HCC tissues of different pathological grades (I, II and
      III)were 40.0%(4/10), 70.0%(14/20) and 100%(12/12), respectively. The expression
      of hTERT was correlated with HCC recurrence. CONCLUSION: The expression of hTERT
      gene may relate to the genesis and progression of HCC. There is no significant
      correlation between the expression of hTERT and PCNA and P53. The detection of
      hTERT gene expression may be regarded as a marker for recurrence of HCC.

PMID- 15555446
TI  - [The changes of expression level of matrix metalloprotease 9 and its inhibitor
      (TIMP-1) in murine pulmonary fibrosis model].
AB  - AIM: To evaluate the balance between matrix metalloprotease-9 (MMP-9) and its
      inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1) in bleomycin-induced
      pulmonary fibrosis in mice. METHODS: Pulmonary fibrosis model was induced by
      bleomycin in mice. The histological images of lungs were studied by HE staining.
      Alveolar macrophages(AMs) were separated by anti-CD68 mAbs using immunomagnetic
      beads(d</=50 nm). The purity of AMs was determined under microscope. Cell
      viability was evaluated by staining with Hoechst 33258 dye. The secreted MMP-9
      and TIMP-1 were assayed in macrophage supernatants, using quantitative enzyme
      linked immunosorbent assays (ELISA). RESULTS: Collagen deposition was gradually
      increased in the lung tissue of mice on day 1, 3, 7, 14 and 28 after bleomycin
      treatment. The purity of AMs could be increased from (82.5+/-2.5)% to (99.3+/
      0.7)% by mini-magnetic cell sorting system (mini-MACS, P<0.05), and the rate of
      living cells post-MACS was (92.5+/-1.8)% (pre-MACS (92.7+/-2.0)%, P>0.05). The
      concentration of MMP-9 secreted by AMs was gradually decreased on day 1, 3, 7, 14
      and 28, and levels of TIMP-1 gradually increased. CONCLUSION: There was an
      imbalance between macrophage-derived MMP-9 and TIMP-1 in bleomycin-induced
      pulmonary fibrosis in mice.

PMID- 15555447
TI  - [Expression and its clinical significance of p27 protein in cervical carcinoma
      tissues].
AB  - AIM: To investigate the expression of p27 protein and its significance in
      cervical carcinoma tissues. METHODS: The p27 protein expression in 26 normal
      cervical tissues and 48 cervical carcinoma tissues was detected by streptavidin
      peroxidase staining(SP method). RESULTS: The positive rate of p27 protein
      expression in 48 cervical carcinoma tissues was 39.5%, and that in 26 normal
      cervical tissues was 72.7%. The former was obviously lower than the
      latter(P<0.01). In addition, The positive rate of p27 protein in 48 cervical
      carcinoma tissue was correlated with the differentiation degree of the carcinoma,
      clinical phase of the patients and lymph node metastasis. In the poorly
      differentiated cancer cells, advanced phase patients and the patients with lymph
      node metastasis, positive rate of p27 protein expression was the lowest.
      CONCLUSION: The expression of p27 protein is related to differentiation degree of
      cancer cells, clinical phase of the patients and lymph node metastasis. Detection
      of p27 protein expression may be valuable to assess prognosis of the patients
      with cervical carcinoma.

PMID- 15555448
TI  - [Establishment of a method to detect multiple antennae carcinoembryonic antigen
      (MA-CEA) and MA-CEA level in the sera of patients with malignant tumors].
AB  - AIM: To establish a rapid quantitative method to detect the serum multiple
      antennae carcinoembryonic antigen (MA-CEA), and to measure the MA-CEA levels in
      the sera of patients with malignant tumors. METHODS: Neuraminidase (NMD) was used
      to digest the sialic acid at terminals of sugar chains of MA-CEA, and then the
      datura stramonium agglutinin (DSA) and anti-CEA antibody were used to set up
      streptavidin-biotin complex (ABC) system EIA (ABC-EIA) for detecting serum MA-CEA
      levels of 239 patients with carcinomas of lung, stomach, liver, colon and ovary.
      The serum CEA level was determined by ELISA. RESULTS: The level of serum MA-CEA
      was remarkably elevated in the CEA-positive patients with lung cancer. The
      positive rate of MA-CEA was 14.6% in 75 patients with lung cancers, and 47.3% in
      19 CEA-positive patients with lung cancers. The MA-CEA was not detected in the
      sera of other tumor patients. CONCLUSION: We have developed a method for
      detection of MA-CEA levels, which lays the foundation for the differential
      diagnosis of lung cancer and for research on the other multiple antennae tumor
      markers.

PMID- 15555449
TI  - [Enhanced inhibitory effect of MUC1 gene vaccine on breast cancer growth by GM
      CSF].
AB  - AIM: To investigate if GM-CSF adjuvant could enhance the inhibitory effect of the
      MUC1 gene vaccine on EMT6 breast cancer growth. METHODS: Female BALB/c mice were
      immunized intramuscularly with 100 microgram MUC1 gene vaccine 3 times at 3 week
      intervals. On 1, 3 and 5 days after intramuscular immunization, GM-CSF 100
      microL(1 microg/100 microL) was given s.c. respectively. Three weeks after the
      last immunization, tumor challenge experiments were performed by using MUC1
      expressing tumor cell line EMT6. Tumor growth inhibition was observed two weeks
      later. After 43 d of challenge experiments, all mice were killed and tumors were
      weighted. CTL-specific cytotoxicity was detected by (51)Cr release assay.
      RESULTS: After 43 d of challenge experiments, the size of EMT6 tumor in MUC1
      DNA+GM-CSF, MUC1 DNA, pcDNA3.1(+)+GM-CSF and pcDNA3.1(+) group were (135+/-33.8)
      mm(3), (250+/-34.3) mm(3), (568+/-43.6) mm(3) and (596+/-48.2) mm(3),
      respectively. The average weight (g) of EMT6 tumors in those four groups were
      0.81+/-0.42, 1.23+/-0.41, 2.30+/-0.48 and 2.28+/-0.58, respectively. EMT6 breast
      cancer growth in mice of MUC1 gene vaccine group was suppressed
      significantly(P<0.05), compared with that in pcDNA3.1(+) control group. Co
      delivery of GM-CSF adjuvant and MUC1 DNA immunization enhanced the antitumour
      effects(P<0.05). The cytotoxicity of MUC1-specific CTLs to EMT6 target cells was
      different at various ratios of effector cells to target cells. At ratios of
      100:1, 50:1, 25:1 and 12.5:1, the specific lysis for MUC1 DNA+GM-CSF group
      reached 68.5%, 53.4%, 35.9% and 28.5%, MUC1 cDNA group 54.1%, 39.8%, 26.4% and
      20.1%, while for control groups 13.2%, 10%, 8.2%, 7.2% and 11.7%, 9.8%, 7.7%,
      7.0%, respectively. GM-CSF enhanced the cytotoxicity of CTL induced by MUC1 DNA
      immunization(P<0.05). CONCLUSION: GM-CSF adjuvant significantly enhanced the
      inhibitory effect of the MUC1 gene vaccine on EMT6 breast cancer growth.

PMID- 15555450
TI  - [IL-18 expression in whole blood cell cultures from active lupus nephritis and
      the inhibitory effects of FK506, cyclosporin A and dexamethasone].
AB  - AIM: To explore the expression of IL-18 in patients with active lupus
      nephritis(LN) and the inhibitory effects of immunosupressive agents FK506,
      cyclosporin A (CsA) and dexamethasone(DEX). METHODS: Peripheral blood samples
      were collected from 16 LN patients and 10 health volunteers and cultured with or
      without PHA/LPS, PHA/LPS+FK506, PHA/LPS+CsA and PHA/LPS+DEX for 24 hours. The IL
      18 level in cultured supernatants and the IL-18 mRNA expression in cultured whole
      blood cells were detected by ELISA and semi-quantitative RT-PCR respectively, and
      the inhibitory effects of FK506, CsA and DEX on IL-18 expression were
      investigated. RESULTS: The expression levels of IL-18 mRNA and its protein in
      whole blood cell cultures from LN patients were higher than those in normal
      control group (P<0.01) either spontaneously or after stimulation with LPS/PHA.
      FK506, CsA and DEX suppressed significantly the expressions of IL-18 mRNA and its
      protein (P<0.001) in LPS/PHA-stimulated whole blood cell from LN patients. The
      inhibitory effects of FK506, CsA and DEX on the IL-18 protein expression in LN
      patients were stronger than that in normal control group (P<0.01 or P<0.05).
      CONCLUSION: IL-18 may play an important role in the pathogenesis of LN and
      inhibition of IL-18 production may be an useful way to treat LN.

PMID- 15555451
TI  - [Changes and significance of TNF, sIL-2R, IL-6, IL-4 and IFN-gamma levels in
      plasma from the patients with hemorrhagic fever with renal syndrome].
AB  - AIM: To explore the changes of TNF, sIL-2R, IL-6, IL-4 and IFN-gamma levels in
      plasma from patients with hemorrhagic fever with renal syndrome(HFRS) and analyze
      the correlation between these cytokine levels and alanine aminotransferase(ALT)
      level in sera from the patients. METHODS: The cytokine levels were measured by
      double mAb sandwich ELISA. An automatic biochemical detector(RA-1000) was
      employed to determine the ALT level. RESULTS: Levels of TNF, IL-6, IL-4, IFN
      gamma and sIL-2R in plasma from the patients were(95.82+/-12.04), (362.46+/
      141.26), (17.76+/-3.52), (116.18+/-19.80) ng/L and (898 820+/-127 200) U/L,
      respectively. These cytokines in plasma from healthy donors were (17.89+/-1.68),
      (43.81+/-18.08), (4.86+/-1.14), (7.57+/-2.41) ng/L and (66 730+/-29 690) U/L,
      respectively. The cytokine levels of the patients were notably higher than those
      of the healthy donors.(P<0.01). At the same time, the average ALT level in sera
      from the patients was 4.4 fold of that from the healthy donors. Statistical
      analysis showed that levels of TNF, sIL-2R, IL-6 and IFN-gamma were positively
      correlated with ALT level, respectively. CONCLUSION: The HFRS patients have a
      significant increase in both cytokines (TNF, sIL-2R, IL-6 and IFN-gamma) and ALT
      levels. And there is a positive correlation between those cytokine and ALT
      levels, suggesting that the liver injury during HTNV infection may be related to
      the elevation of above cytokine levels.

PMID- 15555452
TI  - [The role of Angelica polysaccharides in inducing effector molecule release by
      peritoneal macrophages].
AB  - AIM: To observe the effect of Angelica polysaccharides on effector molecule
      production by peritoneal macrophages. METHODS: Macrophages were isolated from the
      peritoneal cavity of BALB/c mice and the primary culture was performed. MTT
      colorimetry and spectrophotometry were used to examine the effects of Angelica
      polysaccharides on the releases of effector molecules, such as nitric oxide(NO),
      tumor necrosis factor-alpha(TNF-alpha), and reactive oxygen species(ROS) as well
      as inducible nitric oxide synthase (iNOS) and lysozyme(LSZ) activity by
      peritoneal macrophages. RESULTS: Angelica polysaccharides could promote the
      releases of NO, TNF-alpha and ROS from macrophages and improved iNOS and LSZ
      activities in macrophages. However, Angelica polysaccharides had no direct
      cytotoxicity to tumor cells, but the cultural supernatant of macrophages
      cocultured with Angelica polysaccharides could kill L929 cells. CONCLUSION:
      Angelica polysaccharides can promote the releases of NO, TNF-alpha and ROS by
      macrophages. Angelica polysaccharides may indirectly play the role of anti-tumors
      through increased TNF-alpha production by macrophages.

PMID- 15555454
TI  - [Effects of hypertonic saline on erythrocyte adherence function and bacterial
      infection of hemorrhagic shock rabbits].
AB  - AIM: To explore the effect of hypertonic saline on the erythrocyte adherence
      function and bacterial infection of hemorrhagic shock rabbits. METHODS: 60
      Japanese rabbits were randomly divided into 6 groups, 10 for each group. Artery
      catheterization and heparin were given to the rabbits in group 1 (sham shock
      group). Hemorrhagic shock model was set up by bleeding resulting from carotid
      artery catheter in group 2 (normal saline group )and group 3 (hypertonic saline
      group). 30 minutes after shock, the rabbits in group 1 and group 2 were treated
      with normal saline and balanced salt solution containing 1 x 10(9)/kg E.coli,
      respectively. And the rabbits in group 3 were treated with 75 g/L NaCl solution
      and balanced salt solution containing 1 x 10(9)/kg E.coli. Then the survival
      rates of the rabbits in group 1-3 were observed. Rabbits in group 4-6 were same
      treatment as received, group 1-3, respectively, except that there was no E.coli
      in balanced salt solution. The erythrocyte immune adherence function of rabbits
      in group 4-6 were detected 5 hours after shock by RBC-C3bR and RBC-IC rosette
      forming assays. RESULTS: The survival rate of rabbits in hypertonic saline group
      was significantly higher than that in normal saline group. The RBC-C3bR rosette
      forming rate of the normal saline treated rabbits were pronouncedly decreased,
      while RBC-IC rosette forming rate was notably elevated, as compared with those of
      either sham shock group or hypertonic saline group(P<0.01). Hypertonic saline
      markedly increased RBC C3bR rosette forming rate. CONCLUSION: The above findings
      suggest that hypertonic salt solution can remarkably improve the depressed
      erythrocyte immune adherence function and enhance the rabbit's resistance to
      E.coli challenge after hemorrhagic shock.

PMID- 15555453
TI  - [Relationship between apoptosis of mouse thymic lymphocytes and expressions of
      bax, bcl-2 and bcl-XL after gamma-ray radiation with lethal dose].
AB  - AIM: To observe the relationship between apoptosis of mouse thymic lymphocytes
      and the expressions of bax, bcl-2 and bcl-X(L) after gamma-ray radiation with
      lethal dose and provide the basis for treatment of acute severe radiation
      sickness. METHODS: 250 cleaning-grade C57 mice were randomly divided into 6
      groups and treated with 0, 6, 9, 12, 15 and 20 Gy of whole body single gamma
      irradiation, respectivety. The mice were killed by dislocation and then the
      thymus and peripheral blood samples were taken at 1-28 days and 3-12 months after
      irradiation. The lymphocytic apoptosis was analyzed by TUNEL. The expressions of
      bax, bcl-2 and bcl-X(L) were detected by in situ hybridization and
      immunohistochemical staining. RESULTS: (1)Mouse peripheral leucocytes showed a
      transient elevation at 6 h after radiation and then decreased rapidly. The
      leucocyte's number reduced to minimal level at day 7 after 6 Gy gamma-irradiation
      and returned to basic normal value until one month after radiation. (2)24 h after
      irradiation the apoptotic rate of thymic lymphocytes increased swiftly, and
      apoptotic rate was positively correlated with radiation dose in the range of 6-12
      Gy. There was no such a correlation after >/=15 Gy irradiation. (3)24 h after 6
      Gy irradiation the apoptotic rate of thymic lymphocytes reached the maximal
      level. Afterwards it began to decrease, but still higher than that of control
      group even after 12 months. (4)3 h after 6 Gy radiation the expression of Bax
      protein in thymic lymphocytes increased immediately, and reached the highest
      value at 24 h. On the other hand, the expressions of Bcl-2 and Bcl-X(L) proteins
      reduced evidently at 3 h after radiation, reaching the lowest level at 24 h.
      Analysis of bax and bcl-2 mRNAs was concordant with the protein expression
      results. CONCLUSION: After 6-12 Gy gamma-ray irradiation, the apoptotic rate of
      thymic lymphocytes is positively correlated with the radiation doses, suggesting
      that apoptosis is a major way of thymic lymphocyte death after </=12 Gy
      radiation. Increased Bax and decreased Bcl-X(L) expressions in lymphocyte suggest
      that both of them play an important role in thymic lymphocyte apoptosis caused by
      lethal dose radiation.

PMID- 15555455
TI  - [Study on the TCR Vbeta binding sites in the superantigen staphylococcal
      enterotoxin D].
AB  - AIM: To study TCR Vbeta binding sites of staphylococcal enterotoxin D(SED).
      METHODS: Six SED mutants were constructed by site-directed mutagenesis. The
      activity of promoting T cell proliferation by the mutants was detected by (3)H
      TdR incorporation. For the mutants with decreased mitogenic activity, flow
      cytometry was used detect their MHC-II binding activity and TCR Vbeta
      specificity. RESULTS: Residue N23 played an important role in the interaction of
      SED with human TCR Vbeta5. Residue H26 was probably a SED binding site to human
      TCR Vbetas except for TCR Vbeta5, TCR Vbeta8 and TCR Vbeta12.1. CONCLUSION:
      Residue N23 is a key TCR Vbeta binding site of SED.

PMID- 15555456
TI  - [Study of immune responses induced by human papillomavirus type 18 L1-E6 and L1
      E7 chimeric gene DNA vaccines in mice].
AB  - AIM: To examine the humoral and cellular immunoresponses induced by HPV18 L1-E6
      and L1-E7 chimeric gene DNA vaccines in mice. METHODS: 54 BALB/c mice were
      divided into 9 groups randomly, and then vaccinated with various recombinant
      plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immune adjuvants (pLXHDmB7-2 or LTB)
      through different administration routes (intramuscular or intranasal). After the
      third inoculation, blood samples were taken to measure specific antibody, and
      footpad swelling test was used to detect delayed-type hypersensitivity(DTH). Mice
      were killed and spleens were taken to prepare single spleen cell suspension for
      lymphocyte proliferation assay and CD4(+)/CD8(+), IFN-gamma(+) or IL-4(+) T cells
      double staining FACS assay. And then the pathological changes of the swollen
      footpad were observed. RESULTS: Compared with control, significant
      immunoresponses were observed in different experimental groups. The level of
      specific serum IgG against HPV in experiment groups was much higher than that of
      control group, and intramuscular immunization group had the highest antibody
      level. The footpad from immunized mice injected with virus-like particles was
      swollen and harden, and a large amounts of mononuclear cells can be seen in the
      footpad tissues. Intramuscular immunization groups were superior to intranasal
      immunization groups in DTH response, splenocyte proliferation and CD8(+) IFN
      gamma(+) cell number, while CD4(+) IL-4(+) cell number was higher in intranasal
      immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were
      superior to other groups in immune responses. CONCLUSION: The recombinant
      plasmids could induce strong humoral and cellular immunoresponses in mice.
      Costimulatory molecule B7-2 could enhance the immune responses against HPV18
      induced by the L1-E6 and L1-E7 DNA vaccines when used as an adjuvant.

PMID- 15555457
TI  - [Construction and expression of human EpCAM eukaryotic expression vectors and
      identification of their products].
AB  - AIM: To construct EpCAM eukaryotic expression vectors pIg-EpCAM and pEGFP-EpCAM
      and to express them in COS7 cells. METHODS: EpCAM cDNA was amplified by PCR and
      then inserted into the pIg and pEGFP vectors respectively to construct
      recombinant vectors pIg-EpCAM and pEGFP-EpCAM. The two recombinant vectors were
      transfected into COS7 cells under the mediation of liposome. The expressed EpCAM
      Ig fusion protein was detected by Western blot. The expression of EpCAM-GFP
      fusion protein was observed under fluorescence microscope. RESULTS: DNA
      sequencing demonstrated that EpCAM was correctly cloned into the two vectors. The
      culture supernatant of the pIg-EpCAM-transfected COS7 cells could bind
      effectively to mAb against human IgG Fc. Green fluorescence distributed evenly in
      the cytoplasm and nuclei of pEGFP-transfected COS7 cells, whereas in pEGFP-EpCAM
      transfected COS7 cells, green fluorescence distributed mainly on the surface of
      the cells. CONCLUSION: Two EpCAM eukaryotic expression vectors have been
      constructed and expressed successfully, which lays the foundation for functional
      research of EpCAM and for preparation of mAb to EpCAM.

PMID- 15555458
TI  - [Expression of Notch1 gene in the differentiation of the human embryonic neural
      stem cells to neurons].
AB  - AIM: To explore the expression and role of Notch1 gene in the differentiation of
      the human embryonic neural stem cells to neurons induced by all-trans-retinoic
      acid(ATRA). METHODS: The human embryonic neural stem cells were induced with
      various concentrations of ATRA(0.5, 1, 5 and 10 mumol/L) in vitro.
      Immunofluorescence staining was performed after seven days, and neurons were
      quantified by counting NSE positive cells. Then human embryonic neural stem cells
      were induced to differentiate with 1 mumol/L ATRA. Total RNA was extracted from
      the cells before inducing, induced for 3 days, and for 7 days. The expression of
      Notch1 gene was tested by semi-quantitative RT-PCR. RESULTS: The ratio of neural
      stem cells to differentiate to neurons was improved greatly by ATRA induction as
      compared with control group (P<0.01). 1 mumol/L ATRA was the optimal dose for
      induction of the human embryonic neural stem cell differentiation. The percentage
      of neurons induced by 1 micromol/L ATRA was (29.20+/-1.09)%. The expression of
      Notch1 gene decreased significantly after being treated with ATRA(P<0.001).
      CONCLUSION: ATRA can greatly increase the percentage of neurons in the course of
      inducing the human embryonic neural stem cells to differentiate. Notch1 gene is
      down-regulated when human embryonic neural stem cells differentiate into neurons.

PMID- 15555461
TI  - Is antioxidant use protective of cognitive function in the community-dwelling
      elderly?
AB  - BACKGROUND: The role of oxidative stress in the pathogenesis of diseases such as
      macular degeneration, certain types of cancer, and Alzheimer's disease has
      received much attention. Thus, there is considerable interest in the potential
      contribution of antioxidants to the prevention of these diseases. OBJECTIVE: The
      objective of this study was to determine whether use of supplemental antioxidants
      (vitamins A, C, or E, plus selenium or zinc) was associated with a reduced risk
      of development of cognitive impairment or cognitive decline in a representative
      sample of the community-dwelling elderly. METHODS: The sample consisted of 2082
      nonproxy subjects from the Duke Established Populations for Epidemiologic Studies
      of the Elderly who were not cognitively impaired at the 1989-1990 interview
      (baseline for the present analysis). Medication use was determined during in-home
      interviews. Cognitive function was assessed 3 and 7 years from baseline in terms
      of incident cognitive impairment, as measured on the Short Portable Mental Status
      Questionnaire (SPMSQ) using specific cut points (number of errors) based on race
      and education, and cognitive decline, defined as an increase of > or = 2 errors
      on the SPMSQ. Multivariate analyses were performed using weighted data adjusted
      for sampling design and controlled for sociodemographic characteristics, health
      related behaviors, and health status. RESULTS: At baseline, 224 (10.8%) subjects
      were currently taking a supplement containing an antioxidant. During the follow
      up period, 24.0% of subjects developed cognitive impairment and 34.5% experienced
      cognitive decline. Current antioxidant users had a 34.0% lower risk of developing
      cognitive impairment compared with non-antioxidant users (adjusted relative risk
      [RR], 0.66; 95% CI, 0.44-1.00) and a 29.0% lower risk of experiencing cognitive
      decline (adjusted RR, 0.71; 95% CI, 0.49-1.01). CONCLUSION: The results of this
      analysis suggest a possible beneficial effect of antioxidant use in terms of
      reducing cognitive decline among the community-dwelling elderly.

PMID- 15555462
TI  - Laxative use in the community-dwelling elderly.
AB  - BACKGROUND: Constipation, a common and sometimes severe problem in the elderly,
      is often treated with laxatives. OBJECTIVE: The purpose of this study was to
      determine the prevalence of laxative use and identify determinants of such use
      among representative black and white community-dwelling elderly persons. METHODS:
      This was a cross-sectional survey of 4136 participants at baseline (1986-1987) in
      the Duke University Established Populations for Epidemiologic Studies of the
      Elderly. Data on demographic characteristics, health status, health service use,
      and use of prescription and over-the-counter drugs were collected in
      participants' homes. Use of the following types of laxatives was examined:
      bulking, hyperosmotic, lubricant, stimulant, stool softener, saline, and
      miscellaneous agents. RESULTS: It was found that 10.2% of participants used > or
      =1 laxative. Stimulants and bulking agents were the most commonly used classes.
      Only 11.6% of laxative users reported concurrent consumption of > or =2
      laxatives. Multivariate logistic regression analyses indicated that laxative use
      was more likely in women (adjusted OR, 1.78; 95% CI, 1.34-2.37), those with >4
      physicians visits in the previous year (adjusted OR, 1.72; 95% CI, 1.16-2.53),
      those unable to walk a half mile (adjusted OR, 1.44; 95% CI, 1.11-1.87), and
      those using > or =4 over-the-counter nonlaxative medications (adjusted OR, 2.09;
      95% CI, 1.15-3.81). A nonsignificant association was seen between laxative use
      and the use of anticholinergic agents (adjusted OR, 1.38; 95% CI, 1.00-1.89).
      CONCLUSIONS: Laxative use is common among community-dwelling elderly persons and
      is related to specific factors concerning sociodemographics, health status, and
      access to health care. Studies are needed that examine the impact of laxative use
      on bowel function and quality of life in the elderly.

PMID- 15555463
TI  - Oxcarbazepine, topiramate, zonisamide, and levetiracetam: potential use in
      neuropathic pain.
AB  - BACKGROUND: Oxcarbazepine, topiramate, zonisamide, and levetiracetam are the
      antiepileptic drugs (AEDs) most recently approved by the US Food and Drug
      Administration. Based on the experience with carbamazepine, gabapentin, and
      lamotrigine, these newer AEDs are being investigated for the management of
      neuropathic pain. OBJECTIVE: This article reviews preclinical and clinical data
      on the efficacy and tolerability of these 4 AEDs in the management of neuropathic
      pain, as well as the pharmacokinetics, drug-interaction potential, adverse
      effects, and dosing of these agents, with an emphasis on their use in older
      individuals. METHODS: Relevant studies were identified through a MEDLINE search
      of the Englidh-language literature published between 1986 and May 2003, a review
      of the reference lists of identified articles, and abstracts from the annual
      meetings of the American Academy of Neurology (1986-2002) and the 2003 Annual
      Meeting of the American Pain Society. Search terms were oxcarbazepine,
      topiramate, zonisamide, and levetiracetam. RESULTS: Oxcarbazepine and topiramate
      have been effective in animal models of neuropathic pain. Thirty-four
      publications on the efficacy and tolerability of the 4 agents were identified (25
      case reports/case series, 6 randomized parallel-group studies, and 3 randomized
      crossover studies). The 9 randomized studies were restricted to oxcarbazepine and
      topiramate, and 23 (68%) publications were available in abstract form only. These
      preliminary data suggest that the 4 newer AEDs may be useful in a wide variety of
      neuropathic pain syndromes; however, additional data, including full-length peer
      reviewed reports, are necessary before their true analgesic potential in
      neuropathic pain can be determined. All 4 agents have pharmacodynamic
      interactions with other psychotherapeutic drugs, potentiating adverse central
      nervous system events such as sedation. With the exception of levetiracetam,
      these drugs also have pharmacokinetic interactions with other drugs, although to
      a somewhat lesser extent than carbamazepine. These agents have some unique
      adverse effects not frequently monitored by clinicians, such as hyponatremia,
      nephrolithiasis, acute myopia with secondary angle-closure glaucoma, and weight
      loss. CONCLUSIONS: Based on preliminary data, oxcarbazepine, topiramate,
      zonisamide, and levetiracetam may be useful in the treatment of a wide variety of
      neuropathic pain syndromes, although full publication of the results of
      controlled trials is awaited. These agents are associated with specific adverse
      effects not commonly monitored by clinicians. Of the 4, levetiracetam appears to
      be easiest to use (ie, no need for dose adjustment in organ dysfunction, no need
      for laboratory monitoring) and best tolerated, and has not been associated with
      the unique toxicities seen with oxcarbazepine, topiramate, and zonisamide. The
      ultimate role of these agents in the therapeutic armamentarium against pain
      requires further research and experience. In the interim, these 4 agents should
      be used to treat neuropathic pain in the elderly only when carbamazepine,
      gabapentin, or lamotrigine cannot be used or when the response to the
      aforementioned agents is suboptimal.

PMID- 15555464
TI  - Update on drug-related problems in the elderly.
AB  - BACKGROUND: Although pharmacotherapy for the elderly can treat diseases and
      improve well-being, its benefits can be compromised by drug-related problems.
      OBJECTIVE: This article reviews recent publications concerning drug-related
      problems in the elderly, as well as articles describing the development of 3 sets
      of quality indicators for medication use in the elderly. METHODS: Relevant
      articles were identified through a search of MEDLINE (2002-March 2003) for
      articles on drug-related problems, inappropriate prescribing, and adverse drug
      events in the elderly. RESULTS: The review included 7 articles published in 2002
      and 2003. A study in ambulatory elderly persons reported that approximately 5.0%
      of patients had > or =1 adverse drug event within the previous year. Another
      study found that approximately 20.0% of ambulatory elderly persons used > or =1
      inappropriate drug, as defined by drug utilization review (DUR) criteria, with
      drug-disease interactions and duration of use being the most common drug-related
      problems. A third study involving elderly individuals in assisted living
      facilities found that 16.0% used > or =1 inappropriate drug, as defined by the
      Beers criteria. Another study examined whether inappropriate drug use, as defined
      by the Beers or DUR criteria, was associated with death or a decline in
      functional status; it found that only use of drugs defined as inappropriate by
      DUR criteria (particularly those drugs associated with drug-drug or drug-disease
      interactions) was associated with a decline in the ability to perform basic self
      care. Three studies, 1 from the United States, 1 from the United Kingdom, and 1
      from Canada, described consensus development of quality indicators for drug use
      in the elderly, including drugs to avoid, maximum daily dose, drug duplication,
      limits on duration of use, drug-drug and drug-disease interactions, need for drug
      monitoring, underuse of necessary drugs to treat or prevent common problems, and
      inappropriate drug-administration technique. CONCLUSIONS: Drug-related problems
      are common in elderly patients. Data from recently published studies provide
      guidance to practitioners and directions for future research.

PMID- 15555467
TI  - Use of resources and cost implications of stroke prophylaxis with warfarin for
      patients with nonvalvular atrial fibrillation.
AB  - BACKGROUND: Patients with nonvalvular atrial fibrillation (NVAF) have often been
      excluded from long-term anticoagulant trials, and therefore patients in clinical
      practice may have different risk, compliance, and safety considerations from
      those usually included in such trials. OBJECTIVE: The aim of this study was to
      investigate the use of resources and cost implications of stroke prophylaxis with
      warfarin in NVAF patients in clinical practice. METHODS: New patients with NVAF
      referred to an anticoagulation clinic in the United Kingdom were interviewed in
      person at their first visit and then by telephone every 4 to 6 weeks by an
      investigator. They were asked about bleeding events and extra physician visits,
      procedures, or hospital admissions related to bleeding. They were also asked
      about the method and the cost of transportation to the anticoagulation clinic and
      the costs involved in days of work missed by the patient and caregiver. Costs of
      warfarin treatment consisted of the following: (1) cost of the drug, (2) cost of
      monitoring lie, international normalized ratio, traveling, nurse visits, work
      missed. postage), and (3) costs associated with complications (ie, bleeding
      related physician visits, hospital admissions, related procedures). admissions,
      related procedures). RESULTS: A total of 402 patients were included. Mean (SD)
      age was 72.3 (10.3) years, and 224 patients (55.7%) were men. Mean (SD) follow-up
      was 19 (8.1) months (range, 1-31 months). Annual event rates were 1.7% (95% CI,
      0.4-3.0) for major bleeding and 16.6% (95% CI, 13.0-20.2) for minor bleeding. The
      mean cost of warfarin treatment per patient per month was 11.0 pounds (95% CI,
      10.2-11.6) in patients with no bleeding and 11.9 pounds (95% CI, 10.3-12.5) in
      patients with minor bleeding (P=NS). The cost was significantly higher in
      patients with major bleeding ( 299.0 pounds; 95% CI, 74.6-538.9; P<0.001). The
      total cost of warfarin treatment per patient per year was 159.4 pounds, and the
      cost to prevent 1 stroke per year was 5260.20 pounds. CONCLUSION: In clinical
      practice in the United Kingdom, anticoagulation with warfarin for prevention of
      ischemic stroke appeared to be cost-saving relative to the costs of stroke.

PMID- 15555468
TI  - Trends in the prescription of inappropriate drugs for the elderly between 1995
      and 1999.
AB  - BACKGROUND: Using criteria developed by Beers et al between 1991 and 1997,
      previous studies have reported high levels of inappropriate drug prescribing for
      community-dwelling elderly patients (age>or=65 years). However, it is not known
      whether the Beers criteria have had a beneficial effect on prescribing practices.
      OBJECTIVES: The aims of this study were to compare the prevalence of potentially
      inappropriate drug use (based on the Beers list) among older Americans between
      1995 and 1999; to determine whether any decreases in such use were more likely to
      be the result of improved adherence to guidelines or of replacement of older
      medications by newer drugs; and to examine individual characteristics that place
      elderly patients at increased risk for inappropriate drug use. METHODS: This was
      a panel study involving nationally representative samples of community-dwelling
      elderly persons from the 1995 and 1999 Medicare Current Beneficiary Surveys
      (MCBS). For comparison, data were analyzed from samples of disabled Medicare
      beneficiaries aged <65 years for the same periods. The samples were assessed for
      the use of 36 individual drugs, drug classes, and combinations carrying a risk
      for adverse out comes in the elderly based on the 1997 Beers criteria for drugs
      to be avoided in this population. RESULTS: The study samples contained 7628
      community-dwelling elderly persons from the 1995 MCBS and 8902 from the 1999
      MCBS, and 1863 and 1851 disabled Medicare beneficiaries aged <65 years for the
      respective survey years. The proportion of elderly patients taking >or=1 drug on
      the Beers list declined from 24.8% in 1995 to 21.3% in 1999 (P<0.05). There was a
      nonsignificant increase in the proportion of disabled Medicare beneficiaries
      taking >or=1 drug on the Beers list from 31.1% in 1995 to 31.5% in 1999.
      CONCLUSIONS: There was a significant decline in the use of potentially
      inappropriate drugs by elderly patients between 1995 and 1999, particularly in
      the use of those drugs linked to the most severe outcomes. However, approximately
      7 million elderly patients still received potentially inappropriate drugs in
      1999, underscoring the continued need for effective interventions to improve
      prescribing for this vulnerable population.

PMID- 15555469
TI  - Medication-related predictors of health-related quality of life in glaucoma
      patients enrolled in a medicare health maintenance organization.
AB  - BACKGROUND: Glaucoma is an important public health concern in the United States,
      particularly among older adults (aged >or=65 years). Pharmacologic therapy for
      glaucoma consists mainly of topical eye drops containing beta-blockers or
      prostaglandin analogs. OBJECTIVE: The goal of this study was to assess the
      associations between factors of topical medication use (self reported medication
      compliance, belief in benefit of medication use, usage difficulty, usage
      assistance, and complexity of medication regimen) and health-related quality of
      life (HRQOL) in a cross-sectional population of older patients with glaucoma.
      METHODS: A self-administered, 48-question survey soliciting information on
      medication-taking behaviors, treatmen-trelated factors, and HRQOL was mailed to
      members of a Medicare health maintenance organization who were aged >or=65 years
      and had primary open-angle glaucoma. Two mailings were conducted 4 months apart;
      the second was sent to members whose responses to the first mailing had not yet
      been received. The 12-Item Short-Form Health Survey (SF-12) and the 25-Item
      National Eye Institute Visual Function Questionnaire (VFQ-25) were used to assess
      HRQOL. Other questions addressed perceptions of eye drop use in these patients.
      Multiple regression techniques were used to analyze associations between
      medication-related factors and HRQOL in this population. RESULTS: The
      questionnaire was mailed to 589 patients; 375 responded (218 in the first mailing
      and 157 in the second mailing). A total of 358 responses were complete and
      analyzable (effective response rate, 62%). After controlling for the effects of
      other confounders, we found that self reported difficulty in using eye drops was
      strongly associated with decreased HRQOL (11.5% in VFQ-25 total score and 8.4% in
      SF-12 mental health score, P<0.05). Other medication-related factors that were
      examined were not significantly associated with changes in HRQOL. CONCLUSION:
      Based on our findings, patients aged >or=65 years with glaucoma were likely to
      have significant comorbidity, which affected both visual and general health and
      well-being perception. Additionally, a significant proportion of these patients
      reported difficulty with use of topical medication, which was independently
      associated with a significant decrease in HRQOL. Care of older patients with
      glaucoma should incorporate strategies to minimize the difficulty associated with
      medication use.

PMID- 15555470
TI  - Adverse drug reaction risk factors in older outpatients.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are common in older (age >or=65 years)
      outpatients (prevalence, 5%-35%), but there is no consensus on factors that put
      these patients at high risk for ADRs. Identifying a uniform set of risk factors
      would be helpful to develop risk models for ADRs for older outpatients and to
      implement targeted interventions for those patients at high risk for ADRs.
      OBJECTIVE: The aim of this study was to identify potential risk factors for ADRs
      in older outpatients through a survey of geriatric experts and to determine their
      prevalence. METHODS: A comprehensive literature search was conducted to find
      published articles on ADRs in older patients. Forty-four potential risk factors
      were identified through the literature search and 6 additional factors were
      suggested by the expert panel. Through a modified 2-round survey, based on the
      Delphi consensus method, of an expert panel of 5 physicians and 5 pharmacists,
      the probability that each of these 50 potential factors could contribute
      independently to placing an older outpatient at high risk for an ADR was rated on
      a 5-point Likert scale. After the survey responses were received, means and 95%
      Cls were calculated. Consensus was defined as a lower 95% confidence limit
      >or=4.0. Potential risk factors that reached consensus were then applied to a
      sample of older outpatients to determine their prevalence. RESULTS: After 2
      rounds, the expert panel reached consensus on 21 factors, including 12 medication
      related factors and 9 patient characteristics. The most prevalent medication
      related risk factors were opioid analgesics; warfarin; non-acetylsalicylic acid,
      non-cyclooxygenase-2 nonsteroidal anti-inflammatory drugs; anticholinergics; and
      benzodiazepines. The most prevalent patient characteristics included
      polypharmacy, multiple chronic medical problems, prior ADR, and dementia.
      CONCLUSIONS: An expert panel was able to reach a consensus on potential risk
      factors that increase the risk for ADRs in older outpatients. Many risk factors
      were common in a sample of older outpatients. Future research is needed to
      determine the predictive validity of these risk factors for ADRs in older
      outpatients.

PMID- 15555471
TI  - Phenytoin use in elderly nursing home residents.
AB  - BACKGROUND: Phenytoin (PHT) dosing regimens are often determined based on
      experience in those aged <65 years rather than in those aged >or=65 years.
      OBJECTIVE: The goal of this study was to determine the impact of sex, age,
      receipt of concomitant inhibitors or inducers of PHT metabolism, and albumin
      levels on doses and total serum concentrations of PHT in elderly nursing home
      residents. METHODS: Consulting pharmacists to nursing homes located throughout
      the United States collected data from June 1998 to December 2000. The mean daily
      dose per person and mean total serum PHT concentration were tested for
      statistical differences by sex, age group (6-74, 75-84, and >or=85 years),
      coadministration of PHT inhibitors or inducers, and albumin levels. RESULTS: Data
      were collected from 387 residents (259 women, 128 men) of 112 nursing homes in 19
      states who received PHT and for whom PHT concentrations were available. The mean
      (SD) age of the study population was 79.4 (7.8) years; women constituted 67.0% of
      the study population. The mean (SD) total daily dose and total PHT concentration
      were 4.9 (1.8) mg/kg and 11.7 (6.4) mg/L, respectively. In general, women
      received higher mean (SD) daily doses of PHT compared with men (5.1 [1.8] vs 4.6
      [1.6] mg/kg, respectively; P=0.017) to achieve similar total serum concentrations
      (11.6 [6.4] and 12.0 [6.6] mg/L). PHT doses and serum concentrations were similar
      between age groups. There were no differences in daily doses (mg/kg or mg/d) or
      total serum concentrations of PHT based on concomitant use of inhibitors or
      inducers of PHT metabolism or on albumin levels, CONCLUSIONS: In this study in
      elderly nursing home residents, women received higher doses of PHT than men to
      achieve similar total serum PHT concentrations. There were no differences in
      doses or total serum PHT concentrations by age group, use of concomitant inducers
      or inhibitors of PHT metabolism, or albumin levels.

PMID- 15555474
TI  - Can clinical pharmacy services have a positive impact on drug-related problems
      and health outcomes in community-based older adults?
AB  - BACKGROUND: Although pharmacotherapy can be beneficial in the elderly, it can
      also lead to drug-related problems (DRPs), including untreated indications, drug
      use without an indication, improper drug selection, subtherapeutic dosage,
      overdosage, medication error, medication nonadherence, drug interactions, adverse
      drug reactions, adverse drug withdrawal events, and therapeutic failure.
      OBJECTIVE: The goal of this article was to review evidence from randomized
      controlled studies to determine whether DRPs and the related health outcomes can
      be modified by providing clinical pharmacy services for the elderly in community
      based settings. METHODS: Randomized controlled studies that assessed DRPs and
      health outcomes in persons aged > or =65 years after pharmacist interventions
      were identified through searches of MEDLINE (1970-March 2003), the Cochrane
      Database of Systematic Reviews (through March 2003), and International
      Pharmaceutical Abstracts (1966-March 2003). The search combined the terms
      clinical pharmacists, aged, outcomes, and randomized controlled trial. A manual
      search of the reference lists of identified articles and the authors' own
      materials was also conducted. RESULTS: This literature review included 14
      randomized controlled studies: 5 involved interventions in the home health
      setting, 3 were instituted at hospital discharge with home follow-up, 3 were
      clinic based, 1 was conducted in the community pharmacy setting, and 2 were
      conducted in long-term care facilities. These studies provided considerable
      evidence that clinical pharmacy interventions reduced the occurrence of DRPs in
      the elderly but showed limited evidence that such interventions reduced
      morbidity, mortality, or health care costs. CONCLUSIONS: Future large multicenter
      studies are necessary to test the cost-effectiveness of clinical pharmacy
      services for the community-based elderly and the impact of these services on such
      health outcomes as use of health services, timed functional-status measures, and
      adverse drug reactions.

PMID- 15555475
TI  - Extended-release alfuzosin hydrochloride: a new alpha-adrenergic receptor
      antagonist for symptomatic benign prostatic hyperplasia.
AB  - BACKGROUND: Extended-release (ER) alfuzosin hydrochloride is the most recently
      approved alpha-adrenergic receptor antagonist (AARA) for the management of
      symptomatic benign prostatic hyperplasia (BPH). Although new to the United
      States, alfuzosin has been available in immediate-release (IR) and sustained
      release (SR) formulations in other countries for many years. OBJECTIVE: This
      article reviews data on the pharmacodynamics, pharmacokinetics, efficacy,
      tolerability, drug-interaction potential, and dosing of alfuzosin ER. METHODS:
      Relevant articles were identified through MEDLINE, EMBASE, and International
      Pharmaceutical Abstracts searches of the English-language literature published
      between 1986 and September 2003 using the terms alfuzosin, alpha-adrenergic
      receptor antagonists, and quinazolines. The reference lists of identified
      articles were also searched, as were abstracts from annual meetings of the
      American Urological Association for the past 5 years. Data regarding the ER
      formulation were emphasized, and data involving the IR/SR formulations were
      included only when data for the ER formulation were not available or as needed
      for clarification. RESULTS: In comparative trials with its IR counterpart
      (alfuzosin ER 10 mg QD vs alfuzosin IR 2.5 mg TID), alfuzosin ER was an
      equieffective once-daily AARA. No comparative trials of alfuzosin ER with the SR
      (BID) formulation or with other AARAs were identified. Food has been found to
      exert a clinically important effect by enhancing the bioavailability of the ER
      formulation; thus, the drug should be taken on a full stomach. Hepatic impairment
      has been found to significantly delay the elimination of alfuzosin IF, which
      constitutes a contraindication to use of the ER formulation. Renal impairment
      does not appear to exert clinically important effects on the pharmacokinetics of
      alfuzosin ER. Adverse events with alfuzosin ER include dizziness, upper
      respiratory tract infection, headache, and fatigue, with hypotension and syncope
      reported rarely. Concurrent use of inhibitors of the cytochrome P450 3A4 isozyme
      (eg, ketoconazole, diltiazem, cimetidine, atenolol) can significantly elevate
      serum concentrations of alfuzosin and enhance its pharmacodynamic effects.
      CONCLUSIONS: In the absence of direct head-to-head comparative trials, the role
      of alfuzosin ER in the management of symptomatic BPH relative to that of other
      AARAs is unclear. Because the effect size (drug response minus placebo response)
      of alfuzosin ER is comparable to that of other AARAs, marked differences in
      efficacy are unlikely. Extrapolating from direct comparative trials between these
      agents and alfuzosin IR/SR, alfuzosin ER would be expected to have better
      cardiovascular tolerability (eg, in terms of dizziness and orthostasis) than
      prazosin, terazosin, or doxazosin, and to have similar tolerability to
      tamsulosin. However, the existing data do not suggest that alfuzosin ER is likely
      to represent a significant advance over tamsulosin.

PMID- 15555476
TI  - Comparison of anti-infective drug use in elderly persons in Manitoba, Nova
      Scotia, and Saskatchewan, Canada: relationship to drug insurance reimbursement
      policies.
AB  - BACKGROUND: Antimicrobial drug resistance continues to be a concern.
      Inappropriate use of antimicrobial agents is a well-documented contributory
      factor in the development of resistance. Canadian publicly funded drug insurance
      (pharmacare) programs have various approaches to reimbursement for antimicrobial
      drugs and promoting the appropriate prescribing of these agents. OBJECTIVE: The
      objective of this study was to examine changes in antimicrobial use over a 3-year
      period in relation to the reimbursement policies of the public drug insurance
      programs for elderly persons in Manitoba, Nova Scotia, and Saskatchewan. METHODS:
      The pharmacare databases of the 3 provincial drug insurance programs were
      accessed for fiscal years 1995/96, 1996/97, and 1997/98. Antimicrobial drug use
      was reported as mean age- and sex-standardized defined daily doses (DDDs)
      dispensed per 1000 beneficiaries per year. Provincial antimicrobial drug use was
      compared and related to provincial reimbursement policies. RESULTS: The rates and
      types of antimicrobial drugs dispensed to elderly beneficiaries of the Manitoba,
      Nova Scotia, and Saskatchewan pharmacare programs varied. Between fiscal years
      1995/96 and 1997/98, DDDs of antimicrobials per 1000 beneficiaries per year
      decreased by 11.5% in Saskatchewan and increased by 1.2% in Manitoba and 6.2% in
      Nova Scotia. Rates of use of broadspectrum agents such as
      amoxicillin/clavulanate, azithromycin, clarithromycin, and fluoroquinolones were
      lower in the provinces that had reimbursement guidelines. Even when reimbursement
      policies were similar, as for fluoroquinolones in Manitoba and Saskatchewan,
      rates of use varied markedly, possibly as a result of the method of implementing
      the reimbursement guidelines. Use of fluoroquinolones, macrolides, penicillins,
      beta-lactamase-resistant penicillins, and tetracyclines was lower and use of
      sulfonamides and trimethoprim was greater in Saskatchewan than in Nova Scotia and
      Manitoba. CONCLUSIONS: The reimbursement guidelines of provincial drug insurance
      programs are among the factors affecting the use of antimicrobial agents. Both
      the type of reimbursement policy and the policy implementation mechanism affected
      the rate of utilization. Further research is needed to link drug-use information
      with data such as antimicrobial resistance patterns, diagnoses, physician visits,
      and hospitalizations.

PMID- 15555477
TI  - A conceptual framework to study medication adherence in older adults.
AB  - BACKGROUND: Adults aged > or =50 years often have multiple chronic diseases
      requiring multiple medications. However, even drugs with well-documented benefits
      are often not taken as prescribed, for a variety of reasons. OBJECTIVE: The
      objective of this article was to provide background information about medication
      adherence and its measurement, the development of the conceptual model for use in
      adherence research, and supportive intervention strategies such as pharmaceutical
      care by pharmacists to improve chronic medication use in older adults. METHODS:
      English-language literature published from 1990 to 2000 was searched on MEDLINE,
      International Pharmaceutical Abstracts, and AARP Ageline using the terms aged,
      heart failure, CHF, adherence, chronic heart failure, compliance, and related
      terms. The authors used their personal files and libraries to obtain seminal
      literature and textbooks published before 1990. RESULTS: Although the cognitive
      processes needed to manage and take medications decline with aging, the number of
      prescription and nonprescription medications consumed increases. Other factors
      such as vision, hearing, health literacy, disability, and social and financial
      resources may all complicate the ability of older adults to adhere to the
      pharmacologic prescription. CONCLUSIONS: Many factors are associated with
      medication adherence and related health outcomes in older adults. Therefore,
      strategies to improve adherence will need to be multidimensional, including
      improvements in pharmacy services that consider age-related factors (eg,
      declining cognitive and physical functions) as well as a variety of environmental
      and social factors.

PMID- 15555478
TI  - Patient-centered instructions for medications prescribed for the treatment of
      heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is associated with reduced functional
      capacity and quality of life, particularly among older adults. Complex medication
      regimens for CHF challenge older patients' ability to adhere to them, in part
      because of age-related cognitive decline and poor communication about
      medications. OBJECTIVE: This article describes patient-centered instructions for
      taking CHF medications that were developed as part of a multifaceted pharmacy
      based intervention to improve medication adherence and health-related outcomes
      among older adults with CHF. The findings of 3 initial validation studies
      investigating patients' reactions to the instructions are reported. METHODS:
      Patients' responses to the instructions were measured using focus group (study 1)
      and questionnaire (studies 2 and 3) techniques. RESULTS: Overall, older adults
      with CHF in the 3 studies preferred the patient-centered instructions to the
      standard pharmacy instructions (93.8% in study 1, 65.0% in study 2). In addition,
      participants' preferences depended on their medication-related goals. A
      preference for patient-centered instructions reflected a focus on ease of
      understanding (as supported by the use of large type size, icons, and patient
      centered organization), whereas a preference for the standard pharmacy
      instructions reflected a focus on the amount of information provided about drug
      interactions (studies 2 and 3). CONCLUSIONS: In the 3 validation studies, older
      adults with CHF tended to prefer the patient-centered instructions to the
      standard pharmacy instructions, although the results were not statistically
      significant in study 2. This suggests that the use of such instructions may
      improve patients' medication knowledge and their adherence to treatment regimens.

PMID- 15555479
TI  - Methodology of an ongoing, randomized, controlled trial to improve drug use for
      elderly patients with chronic heart failure.
AB  - BACKGROUND: Medications can improve the functioning and health-related quality of
      life of patients with chronic heart failure (CHF) and reduce morbidity,
      mortality, and costs of treatment. However, patients may not adhere to therapy.
      Patients with complex medication regimens and low health literacy are at risk for
      nonadherence. OBJECTIVE: The primary goal of this project is to develop and
      assess a multilevel pharmacy-based program to improve patient medication
      adherence and health outcomes for elderly CHF patients with low health literacy.
      METHODS: In this 4-year, controlled trial, patients aged 50 years with a
      diagnosis of CHF who are being treated at Wishard Health Services (Indianapolis,
      Indiana) are randomly assigned to pharmacist intervention or usual care.
      Intervention patients receive 9 months of pharmacist support and 3 months of
      postintervention follow-up. The intervention involves a pharmacist providing
      verbal and written education, icon-based labeling of medication containers, and
      therapeutic monitoring. The pharmacist identifies patients' barriers to
      appropriate drug use, coaches them on overcoming these barriers, and coordinates
      medication use issues with their primary care providers. Daily updates of
      relevant monitoring data are delivered via an electronic medical record system
      and stored in a personal computer system designed to support pharmacist
      monitoring and facilitate documentation of interventions. To measure medication
      adherence objectively, electronic monitoring lids are used on all CHF medications
      for patients in both study groups. Other assessments include self-reported
      medication adherence, results of echocardiography (eg, ejection fraction), brain
      natriuretic peptide concentrations, and health-related quality of life. Health
      services utilization, refill adherence, and cost data derive from electronic
      medical records. After completion of this study, the data can be used to assess
      the effectiveness and cost-effectiveness of our intervention. RESULTS: One
      hundred twenty-two patients have been assigned to receive the intervention and
      192 to receive usual care. CONCLUSIONS: Our study aims to improve patients'
      knowledge and self-management of their medication and to improve medication
      monitoring in a multilevel pharmacy-based intervention. By doing so, we intend
      that the intervention will improve the health outcomes of elderly patients with
      CHF.

PMID- 15555480
TI  - Zolpidem prescribing and adverse drug reactions in hospitalized general medicine
      patients at a Veterans Affairs hospital.
AB  - BACKGROUND: Zolpidem is prescribed for sleep disruption in hospitalized patients,
      but data on the incidence of adverse drug reactions (ADRs) are based largely on
      outpatient studies. Thus, the incidence of ADRs in hospitalized patients may be
      much higher. OBJECTIVE: The goal of this study was to describe prescribing
      patterns of zolpidem for hospitalized medical patients aged 50 years, the
      incidence of ADRs possibly and probably associated with its use, and the factors
      associated with central nervous system (CNS) ADRs. METHODS: This case series was
      conducted in 4 general medicine wards at a Veterans Affairs hospital and was a
      consecutive sample of patients aged 50 years who were hospitalized between 1993
      and 1997 and received zolpidem as a hypnotic during hospitalization, but had not
      received it in the previous 3 months. Chart review was conducted by 2 evaluators.
      Data extracted from the medical records included admission demographic
      characteristics, medications, comorbidities, and levels of function in performing
      basic and instrumental activities of daily living. The main outcome measure was
      ADRs possibly or probably related to zolpidem use. The association between
      zolpidem and the occurrence of CNS ADRs (eg, confusion, dizziness, daytime
      somnolence) was analyzed separately. RESULTS: The review included 119 medical
      patients aged > or =50 years who had newly received zolpidem for sleep disruption
      during hospitalization. The median age of the population was 70 years; 86 (72.3%)
      patients were aged 65 years. The initial zolpidem dose was 5 mg in 42 patients
      (35.3%) and 10 mg in 77 patients (64.7%). Twenty-three patients had a respective
      16 and 10 ADRs possibly and probably related to zolpidem use (19.3% incidence).
      Of a total of 26 ADRs, 21 (80.8%) were CNS ADRs, occurring with both zolpidem 5
      mg (10.8% of users) and 10 mg (18.3% of users). On univariate analyses, the only
      factor significantly associated with a CNS ADR was functional impairment at
      baseline (P = 0.003). Zolpidem was discontinued in 38.8% of patients experiencing
      a CNS ADR CONCLUSIONS: In this case series in medical inpatients, there was a
      high frequency of ADRs, particularly CNS ADRs, associated with zolpidem use.
      Zolpidem should be used cautiously in the hospital setting.

PMID- 15555481
TI  - Navigating the new Medicare drug benefit.
AB  - BACKGROUND: Medicare beneficiaries have had to wait 40 years for an outpatient
      prescription drug benefit. On December 8, 2003, President Bush signed into law
      the Medicare Prescription Drug, Improvement and Modernization Act of 2003 that
      will provide at least limited drug coverage to all beneficiaries who sign up for
      it. OBJECTIVE: The aim of this commentary is to provide a basic appreciation of
      the mechanics of the new drug benefit and an analysis of why it looks the way it
      does. CONCLUSIONS: A combination of ideology and spending constraints led
      Congress to develop a benefit package that while generous for low-income
      beneficiaries with limited assets, has significant gaps in coverage for everyone
      else. After a transitional program of discount cards that will carry them through
      2005, beneficiaries will have to choose their source of prescription benefits
      from private stand-alone drug plans, managed care organizations, or (if available
      to them) employer-sponsored plans. The structure of the benefit is a radical
      departure from the way other Medicare benefits are provided and paid for, and
      raises a number of important questions. Will sufficient numbers of risk-bearing
      private drug plans enroll in the program for competition to work? Will employers
      maintain retiree drug coverage? Will the new program stop the slide in Medicare
      managed care? How will beneficiaries react when the law is explained in ways they
      truly understand? The answers to these questions will help determine the success
      or failure of drug coverage under Medicare.

PMID- 15555485
TI  - Impact of inappropriate drug use on health services utilization among
      representative older community-dwelling residents.
AB  - BACKGROUND: There is limited objective information regarding the impact of drugs
      identified as inappropriate by drug utilization review (DUR) or the Beers drugs
      to-avoid criteria on health service use. OBJECTIVE: The goal of this study was to
      examine the predictive validity of DUR and the Beers criteria employed to define
      inappropriate drug use in representative community residents, aged >or=68 years,
      as determined by the relationship of these criteria to health service use in
      older community residents. METHODS: Data came from participants in the Duke
      University Established Populations for Epidemiologic Studies of the Elderly seen
      in 1989/1990 and for whom information was also available 3 years later. Two sets
      of inappropriate drug use criteria were examined: (1) DUR regarding dosage,
      duration, duplication, and drug-drug and drug-disease interactions; and (2) the
      Beers criteria, applied to drug use reported in an in-home interview. Outpatient
      visits and nursing-home entry were determined by personal report; hospitalization
      information came from Medicare Part A files from the Centers for Medicare and
      Medicaid Services. RESULTS: A total of 3165 participants were available at the
      fourth interview in 1989/1990. The majority were aged >74 years (51.1%), white
      (64.8%), women (64.7%), had fair or poor health (77.0%), consistently saw the
      same physician (86.9%), and possessed supplemental health insurance (62.8%). Use
      of inappropriate drugs meeting DUR criteria, especially for drug-drug or drug
      disease interaction problems, was associated with increased outpatient visits
      (P<0.05) but not with time to hospitalization or time to nursing home entry. The
      use of inappropriate drugs according to the Beers criteria was associated with
      reduced time to hospitalization (adjusted hazard ratio, 1.20; 95% CI, 1.04-1.39)
      but not to outpatient visits or nursing home entry. CONCLUSIONS: Our data suggest
      that in representative community residents aged >or=68 years, current criteria
      for inappropriate drug use should be used with caution in evaluating quality of
      care because they have minimal impact on use of health services. We found
      increases only in the use of outpatient services (with DUR) and more rapid use of
      hospitalization (with the Beers criteria).

PMID- 15555486
TI  - Prevalence, correlates, and associated outcomes of potentially inappropriate
      psychotropic use in the community-dwelling elderly.
AB  - BACKGROUND: Previous applications of the Beers criteria have shown significant
      prescribing of potentially inappropriate psychotropic agents for the community
      dwelling elderly. However, there is limited information at the national level on
      potentially inappropriate psychotropic use, the characteristics of elderly
      persons at risk, and the impact of this inappropriate use on health care
      outcomes. OBJECTIVE: This study addressed the prevalence, correlates, and
      associated outcomes of potentially inappropriate psychotropic use among community
      dwelling elderly persons in the United States who were receiving psychotropic
      medications. METHODS: Data from the 1996 Medical Expenditure Panel Survey (MEPS)
      were employed to examine the use of psychotropic medications that generally
      should be avoided in the elderly and those that should be avoided in elderly
      patients with certain preexisting conditions, as defined by the Beers criteria.
      The MEPS sampling weights were used to derive national estimates. Cross-sectional
      data were analyzed by multivariate analyses to examine the correlates and
      associated health care outcomes (health care utilization, economic, and
      humanistic) of potentially inappropriate psychotropic use in the elderly.
      RESULTS: An estimated 2.30 million community-dwelling elderly persons received
      potentially inappropriate psychotropic medications in 1996. This represented
      7.14% of all community-dwelling elderly persons and 37.86% of all community
      dwelling elderly persons using psychotropic agents; 32.94% of those taking
      psychotropic drugs received agents that were generally inappropriate, and 10.21%
      received agents that were inappropriate in the presence of specific conditions.
      The rates of potentially inappropriate psychotropic use in those receiving
      antidepressant, antianxiety, and sedative/hypnotic agents were 50.93%, 31.84%,
      and 23.49%, respectively. Multivariate analyses showed that correlates of
      potentially inappropriate psychotropic use in the elderly were age <75 years and
      use of multiple psychotropic agents. After controlling for predisposing,
      enabling, and need factors, no association was found between the use of
      potentially inappropriate psychotropic medications and differences in health care
      utilization, economic, or humanistic outcomes. CONCLUSIONS: The study findings
      suggest that although the use of potentially inappropriate psychotropic
      medications is common among the community-dwelling elderly who are prescribed
      psychotropic agents, the unfavorable risk-benefit ratio of these inappropriate
      medications does not appear to influence broad measures of health care
      utilization, costs, or quality of life in this population.

PMID- 15555487
TI  - Undertreatment of osteoporosis in women, based on detection of vertebral
      compression fractures on chest radiography.
AB  - BACKGROUND: Fractures attributable to ostcoporosis are responsible for
      preventable suffering and health care costs. Until they experience a fracture,
      many older adults, particularly women, are unaware that they have osteoporosis.
      Although radiographs taken for reasons other than evaluating the possibility of
      osteoporosis may suggest the presence of fracture, such fractures often go
      undetected and effective treatments are not implemented. OBJECTIVE: The goal of
      this study was to determine the adequacy of treatment of osteoporotic vertebral
      compression fractures in middle-aged and older women in an internal medicine
      clinic, as ascertained by reports of chest radiography. The hypothesis was that
      patients having chest radiographs with observable vertebral compression fractures
      often did not receive adequate treatment. METHODS: This was a retrospective,
      cross-sectional study conducted at a general internal medicine clinic at a
      university-affiliated county hospital. The records of an academic internal
      medicine practice were searched to identify women aged >or=40 years with
      radiologic evidence of vertebral compression fractures during the period from
      June 1, 1992, through May 31, 2002. Electronic prescription records were then
      searched to determine whether patients had received a prescription for a
      medication for the treatment of osteoporosis. An analysis also was conducted to
      describe the frequency distribution of various medications for the treatment of
      osteoporosis. RESULTS: One hundred thirteen women were identified who met the
      study criteria. Their mean (SD) age was 68.1 (21.9) years. Fifty-six (50%) of
      these women received pharmacologic treatment for osteoporosis. The most commonly
      prescribed medications were estrogens (35%), calcitonin (16%), and
      bisphosphonates (12%). CONCLUSIONS: No more than half of patients identified as
      having a vertebral compression fracture on chest radiography received even 1
      prescription for the treatment of osteoporosis. Because this study did not
      examine adherence or long-term medication use, the proportion of women who
      received adequate osteoporosis therapy was probably much less than half.
      Physicians should be alert to the possible presence of vertebral compression
      fractures and take a more aggressive approach to treatment when a fracture is
      present.

PMID- 15555488
TI  - Pharmacotherapeutic approaches to the prevention of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common cause of cognitive
      impairment in older patients and is expected to increase greatly in prevalence.
      Interventions that could delay disease onset would have a major public health
      impact. OBJECTIVE: The objective of this article is to review evidence from
      epidemiologic studies and controlled trials addressing whether AD can be
      prevented. METHODS: Data were gathered through a comprehensive, systematic search
      of MEDLINE using focused search criteria and spanning a 6-year period from
      January 1998 through January 2004; a hand search of reference lists from these
      studies and reviews; a review of the Cochrane Database of Systematic Reviews; and
      a hand search of relevant journals. Selection of articles was based on the
      clinical focus. Additional inclusion criteria were used to select key articles
      that contained higher-level evidence in accordance with explicit, validated
      criteria. RESULTS: Preventive interventions for AD include vitamins, nonsteroidal
      anti-inflammatory drugs, and agents that protect the endothelium (eg, statins).
      Good control of hypertension with angiotensin-converting enzyme inhibitors and
      long-acting dihydropyridines also confers neuroprotective benefits. CONCLUSIONS:
      The paradigm that AD is pharmacologically unresponsive is shifting as more
      effective pharmacotherapies for prevention and treatment rapidly emerge. Our
      understanding of the molecular mechanisms of neurodegeneration will soon allow us
      to more specifically target and interrupt the processes that contribute to this
      progressive dementia.

PMID- 15555489
TI  - Medication use among black and white caregivers of older male veterans with
      dementia.
AB  - BACKGROUND: Few studies have examined racial differences in medication use among
      informal caregivers of elderly individuals with progressive dementia. It is
      important to identify racial disparities in medication use so that these
      differences can be corrected. OBJECTIVE: The purpose of the current study was (1)
      to evaluate whether black caregivers were less likely to be taking medication
      than white caregivers after controlling for specific factors and (2) to examine
      the relationship between caregiver race and other predisposing, enabling, and
      need factors, and the use of specific categories of medications. METHODS: A
      secondary analysis of data was conducted from a national survey of 2032 black and
      white female caregivers of elderly male US veterans with a diagnosis of
      Alzheimer's disease or vascular dementia. Caregiver use of specific medications
      was classified according to the Veterans Affairs medication classification
      system. The Andersen Behavioral Model of Health Services Use provided a framework
      for multivariate models predicting racial differences in any medication use and
      use of specific categories of medications. RESULTS: Black caregivers were
      significantly less likely to use any medication than white caregivers (adjusted
      odds ratio [OR]=0.42; 95% CI=0.31-0.57). These differences persisted even after
      controlling for other predisposing, enabling, and need factors, and for
      outpatient doctor visits. Black caregivers were significantly less likely than
      white caregivers to be taking endocrine/metabolic medications (adjusted OR=0.57;
      95% CI=0.42-0.77) and central nervous system medications (adjusted OR=0.57; 95%
      CI=0.39-0.83). CONCLUSION: The results of this analysis suggest that significant
      racial differences in medication use exist among informal caregivers providing
      care for elderly male US veterans with progressive dementia.

PMID- 15555490
TI  - A new tool for identifying discrepancies in postacute medications for community
      dwelling older adults.
AB  - BACKGROUND: Despite a national focus on the problem of medication safety, few
      studies have examined the frequency, causes, and factors contributing to
      discrepancies between the medications prescribed in acute care settings and what
      elderly patients (age>or=65 years) actually take after their discharge.
      OBJECTIVE: The aims of this study were to develop a new instrument, the
      Medication Discrepancy Tool (MDT), for use by multiple practitioners across the
      continuum of care and to assess the MDT's reliability among nurses, pharmacists,
      and physicians, all of whom play a part in the formulation and administration of
      medication regimens for patients in transition. METHODS: The study was conducted
      in a vertically integrated health care system and at a geriatric clinic in an
      academic health center. We applied the MDT to a series of 20 clinical vignettes
      based on actual cases involving older patients discharged from a community
      hospital to home. The interrater reliability of the MDT was assessed by asking
      clinicians (2 home health care nurses, 2 doctoral-trained geriatric pharmacists,
      and 2 physicians) to use this tool to rate the clinical vignettes. Reliability
      comparisons were then made within and across clinical disciplines. Intrarater
      reliability was also determined. RESULTS: Across all 3 clinical disciplines, the
      mean interrater reliability (kappa) for the 20 vignettes was 0.56 (15% low
      agreement, 80% good agreement, and 5% excellent agreement). Within disciplines,
      the kappa statistic was as follows: nurses, 0.68; pharmacists, 0.50; and
      physicians, 0.64. Intrarater reliability ranged from 0.58 to 0.69. CONCLUSIONS:
      By capturing transition-related medication discrepancies, the MDT fills an
      important gap in national efforts to promote patient safety. MDT items are
      actionable at both the patient and system level, suggesting that this tool could
      be used to foster continuous quality improvement efforts.

PMID- 15555492
TI  - Gonadal hormones provide the biological basis for sex differences in behavioral
      responses to cocaine.
AB  - Both clinical and rodent studies show sexually dimorphic patterns in the
      behavioral response to cocaine in all phases of the addiction process (induction,
      maintenance, and relapse). Clinical and rodent studies also indicate that
      hormonal fluctuations during the menstrual/estrous cycle modulate cocaine-induced
      subjective effects in women and locomotor activity in female rats. Evidence
      suggests that gonadal hormones underlie these observed differences and could be
      the biological basis of sex-specific differences in cocaine addiction. To study
      the effects of gonadal hormones on cocaine-induced activity, two approaches have
      been used. First, studies have examined the role of endogenous hormones through
      gonadectomy (GDX) and side-by-side comparisons with intact rats. Second, the
      individual contributions of testosterone, progesterone, and estrogen have been
      determined by hormone replacement in GDX rats. In this review, we discuss gonadal
      hormones as the biological basis for the behavioral responses to cocaine, and the
      clinical implications of these findings.

PMID- 15555493
TI  - Hormonal correlates of changes in interest in unrelated infants across the
      peripartum period in female baboons (Papio hamadryas anubis sp.).
AB  - In past research on human and nonhuman primates, maternal responsiveness and
      behavior has been thought of as an experiential, cognitive mechanism; however,
      recent findings have shown that maternal motivation and behavior may not be
      entirely divorced from the endocrine system. To investigate the relationship
      between interest in infants and the hormonal changes related to pregnancy, we
      examined the nature of social interactions across parturition between a large
      sample (n = 133) of adult female baboons (Papio hamadryas anubis sp.) and
      unrelated infants. Prepartum data were collected during ten 30-min focal
      observations for each subject. Each mother-infant pair was then observed through
      the infant's first 8 weeks of life. A total of 2325 h of observation was
      recorded. Urine was collected on 65 subjects, starting 5 weeks before the
      expected date of parturition and ending 4 weeks after parturition. Evidence for a
      connection between endocrine function and responsiveness toward infants was
      found. Affiliative behaviors during the prepartum period were positively
      correlated to the estrogen/cortisol ratio and high dominance rank. In the
      postpartum period, affiliative behaviors were positively correlated with
      prepartum progesterone and dominance rank, and negatively correlated with
      postpartum cortisol levels. Finally, a positive correlation was recorded during
      the postpartum period between prepartum progesterone and aggression, and a
      negative correlation between postpartum cortisol and aggression and submission.
      Our data suggest that the endocrine changes that may help regulate maternal care
      of offspring also influence the way in which pre- and postpartum female baboons
      interact with unrelated infants in their social group.

PMID- 15555494
TI  - Prepartum plasma estradiol and postpartum cortisol, but not oxytocin, are
      associated with interindividual and breed differences in the expression of
      maternal behaviour in sheep.
AB  - Consistent, individual differences in the expression of maternal behaviour have
      been described in several species including the sheep. The neuroendocrine
      mechanisms underlying the onset of maternal behaviour in the sheep have been
      described, although the relationship between hormonal events and individual
      differences in behaviour has yet to be determined. In this study, we examined
      whether the individual differences in plasma estradiol, progesterone, oxytocin
      and cortisol concentrations were related to observed individual and breed
      differences in maternal behaviours in two breeds of sheep (Scottish Blackface and
      Suffolk) known to differ in maternal behavioural expression. Maternal estradiol
      concentration increased rapidly before parturition and was higher in Blackface
      ewes than Suffolk ewes. Plasma progesterone declined before parturition and was
      higher in Suffolk than Blackface ewes. Prepartum estradiol, but not progesterone,
      was related to individual differences in maternal grooming of the lamb. Plasma
      oxytocin did not differ between breeds in late gestation. There was a tendency
      for oxytocin to be higher in Blackface than Suffolk ewes immediately after birth.
      However, there were no significant relationships between prepartum or postpartum
      oxytocin and any maternal behaviours. Plasma cortisol was higher in Blackface
      than Suffolk ewes in the last days of pregnancy but rose in both breeds over the
      last 24 h before parturition and did not differ at delivery. Cortisol peripartum
      was negatively related to individual differences in maternal affiliative
      behaviours. These data suggest that estradiol, and potentially cortisol, may
      mediate individual differences in maternal behaviour in sheep.

PMID- 15555495
TI  - Female-induced sexual arousal in male mice and rats: behavioral and testosterone
      response.
AB  - Exposure of a male mouse to a female mouse separated from it by a holed partition
      induced specific behavior and an increase in blood testosterone in the male. The
      male made more approaches to the partition and spent more time at it. The time
      spent by the male mouse over the first 10 min at the partition, behind which an
      estrus female was placed, was increased sixfold compared to the time spent by a
      male mouse exposed to the vacant neighboring compartment; and 1.5-fold compared
      to that spent by a male mouse exposed to a nonreceptive female or a male.
      Increased blood testosterone level was detected at 20 min of exposure to a
      receptive female in winter and at 40 min in summer. No variation in blood
      testosterone levels in the male mouse exposed to a nonreceptive female or a male
      was observed. Similar response to a receptive female placed in the neighboring
      compartment was shown in a male rat. The time spent by the male rat at the
      partition was 12 times higher when there was an estrus female behind it than in
      control. Blood testosterone in the male rat increased in response to a female rat
      and did not change in response to a male rat indicating female-induced
      motivation. It was concluded that the partition time might serve as a
      quantitative measure of sexual motivation in the males and that the model of
      female-induced sexual arousal used was suitable for studying both motivational
      and hormonal components of sexual arousal in male mice and rats.

PMID- 15555496
TI  - Stimulation of sexual behavior in the male rat by galanin-like peptide.
AB  - Galanin-like peptide (GALP) is a recently described neuropeptide, which shares a
      partial sequence identity with galanin but is derived from a separate gene.
      Central injections of GALP stimulate the secretion of gonadotropin-releasing
      hormone (GnRH) and luteinizing hormone (LH) and induce the expression of Fos in
      several brain areas known to regulate male sexual behavior in the rat. We
      postulated that GALP may also stimulate sexual behavior in concert with its
      stimulatory effect on the hypothalamic-pituitary-gonadal (HPG) axis. To test this
      hypothesis, we administered GALP, galanin, or the vehicle (artificial
      cerebrospinal fluid, aCSF) alone to sexually experienced male rats and assessed
      the effects of these agents on sexual behavior. We observed that compared to aCSF
      alone, GALP significantly increased all aspects of male-typical sexual behavior,
      whereas galanin inhibited all of these same behaviors. To examine whether the
      stimulatory effects of GALP on sexual behavior were mediated by GALP's
      stimulatory effects on the HPG axis, we castrated the same male rats and repeated
      the behavioral experiment. We found that GALP maintained its inductive action on
      male-typical sexual behaviors in the castrated animals, suggesting that the
      effects of GALP on sexual behavior are not the result of GALP's ability to
      stimulate testosterone secretion. These observations suggest that GALP neurons
      are part of the hypothalamic circuitry controlling sexual behavior in the male
      rat.

PMID- 15555497
TI  - Digit length ratios predict reactive aggression in women, but not in men.
AB  - Considerable evidence suggests that digit length and dermatoglyphic asymmetry
      patterns in the hand are affected by early exposure to androgens. Because
      androgens play an important role in sexual differentiation of morphological and
      behavioral traits, digit length patterns often display sex differences. When
      present, sex differences in digit lengths are more pronounced on the right side
      as compared to the left side. Moreover, the ratio of the second to fourth digit
      length (2D:4D) in the right hand is inversely correlated with testosterone (T) in
      men. Because T is implicated in agonistic behavior, 2D:4D may be used as a marker
      of androgen exposure and subsequent behavioral variation in adulthood.
      Consequently, we investigated the relationships among 2D:4D, directional
      asymmetry of 2D:4D (left hand 2D:4D minus right hand 2D:4D) as a variant of T,
      and human reactive aggression. One hundred young men (n = 51) and women (n = 49)
      participated in our experiments (mean age = 20.1 years). Participants called two
      noncompliant confederates to solicit donations for a fictitious charity
      organization and selected follow-up letters after the calls. The force exerted
      when hanging up the phone and the "tone" of the follow-up letters were used to
      assess reactive aggression. High aggression scores were associated with high
      directional asymmetry of 2D:4D and masculinized (low) right hand 2D:4D, only in
      females and under high provocation. Directional asymmetry of 2D:4D was positively
      correlated with T in males (pooled data, n = 97). Taken together, these data
      confirm the predominantly right-sided influence of androgens on digit length and
      suggest that digit length ratios may be associated with female reactive
      aggression when sufficient provocation is present.

PMID- 15555498
TI  - Food supplementation and possible mechanisms underlying early breeding in the
      Florida Scrub-Jay (Aphelocoma coerulescens).
AB  - Food supplementation studies demonstrate the importance of resources in the
      timing of reproduction. Studies of Florida Scrub-Jays (Aphelocoma coerulescens)
      found that supplemented jays bred earlier than unsupplemented jays and that
      protein may play a critical role. In this study, free-living scrub-jays were
      provided with supplemental diets high in fat and protein (HFHP) or high in fat
      and low in protein (HFLP). Jays in both treatments bred earlier than
      unsupplemented controls (CNT), but HFHP-supplemented jays bred earlier than HFLP
      jays. To assess possible mechanisms, we measured testosterone (T) in males,
      estradiol (E2) in females, and corticosterone (CORT) in both. HFHP males had
      higher T than HFLP and CNT males, but treatment did not affect E2 levels of
      females. Pilot studies of scrub-jays in suburban environments suggest that the
      spatial and temporal predictability of food may influence corticosterone (CORT)
      levels. Suburban jays have year-round access to human-provided foods and breed
      earlier than wildland jays; thus, we compared CORT in all treatments in the
      natural site (wildlands) with those of suburban jays. CORT levels of suburban
      jays were lower than HFLP, HFHP, and CNT jays. HFHP-supplemented jays had lower
      CORT levels than those of HFLP and CNT jays. The observed differences in the
      timing of breeding, both between suburban and wildland populations and between
      experimental groups in the wildlands, may result from differences in the spatial
      and temporal predictability of food, and the nutritional differences in diets.
      Because CORT can negatively affect the reproductive axis, we postulate that
      nutrient availability, the predictability of food, CORT levels, and initiation of
      reproduction are inextricably linked.

PMID- 15555499
TI  - Plasma corticosterone increases during migratory restlessness in the captive
      white-crowned sparrow Zonotrichia leucophrys gambelli.
AB  - Plasma corticosterone increases during the period of spring migration in a
      variety of bird species. Long-distance migrants show elevations in corticosterone
      specifically in association with the stage of flight, suggesting that
      corticosterone may support flight-related processes, for example, locomotor
      activity and/or energy mobilization. The pattern of corticosterone secretion as
      it relates to migratory flight has hitherto not been clearly described in
      migrants that frequently interrupt flight to refuel, for example, the Gambel's
      white-crowned sparrow (Zonotrichia leucophrys gambelii). The Gambel's white
      crowned sparrow fuels by day and expresses peak migratory activity during the
      first few hours of night. To determine if plasma corticosterone increases in
      association with the stage of migratory flight also in this short-bout migrant,
      we induced captive white-crowned sparrows to enter into the migratory condition
      by placing photosensitive birds on long days (16L:8D) and then evaluated birds
      for plasma corticosterone and locomotor activity during four time points of the
      day. Patterns found in long-day birds were compared to those observed in short
      day controls (8L:16D). Differences in energy metabolism as determined from plasma
      metabolites were also evaluated. We found that locomotor activity and
      corticosterone were significantly elevated at the onset of the dark period, but
      only in long-day birds. Plasma beta-hydroxybutyrate (a ketone body) was also
      elevated. Thus, findings suggest that plasma corticosterone and ketogenesis
      increase in association with migratory restlessness in a short-bout migrant. In
      fact, corticosterone may play a regulatory role, because it shows a trend to
      increase already before night-time activity.

PMID- 15555500
TI  - Adrenal hormones mediate melatonin-induced increases in aggression in male
      Siberian hamsters (Phodopus sungorus).
AB  - Among the suite of seasonal adaptations displayed by nontropical rodents, some
      species demonstrate increased territorial aggression in short compared with long
      day lengths despite basal levels of testosterone. The precise physiological
      mechanisms mediating seasonal changes in aggression, however, remain largely
      unknown. The goal of the present study was to examine the role of melatonin, as
      well as adrenal hormones, in the regulation of seasonal aggression in male
      Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters
      received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2
      h before lights out for 10 consecutive days. In Experiment 2, hamsters received
      adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received
      adrenalectomies (ADx); control animals in both experiments received sham
      surgeries. Animals in both experiments subsequently received daily injections of
      melatonin or vehicle as in Experiment 1. Animals in all experiments were tested
      using a resident-intruder model of aggression. In Experiment 1, exogenous
      melatonin treatment increased aggression compared with control hamsters. In
      Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment
      3, the melatonin-induced increase in aggression was significantly attenuated by
      ADx. Collectively, the results of the present study demonstrate that short day
      like patterns of melatonin increase aggression in male Siberian hamsters and
      suggest that increased aggression is due, in part, to changes in adrenocortical
      steroids.

PMID- 15555501
TI  - Effects of affiliation and power motivation arousal on salivary progesterone and
      testosterone.
AB  - Following up on earlier research suggesting a link between implicit affiliation
      motivation and progesterone (P) and implicit power motivation and testosterone
      [T; Schultheiss, O.C., Dargel, A., Rohde, W., 2003. Implicit motives and gonadal
      steroid hormones: Effects of menstrual cycle phase, oral contraceptive use, and
      relationship status. Horm. Behav. 43, 293-301.], we tested whether arousal of
      affiliation motivation increases P levels and whether arousal of power motivation
      increases T levels. Sixty subjects were randomly assigned to watch 30 min of
      either Bridges of Madison County (affiliation arousal) or The Godfather II (power
      arousal), or a documentary about the Amazon (control condition). Levels of P and
      T were assessed in saliva samples taken before (T1), immediately after (T2), and
      45 min after the movie (T3). The efficacy of experimental conditions to
      differentially arouse motives was verified by assessment of changes in
      affiliation and power motive imagery expressed in imaginative stories written
      before and after the movie. After the movie, salivary P levels (T2 and T3) in the
      affiliation-arousal group were significantly higher than in the control group and
      marginally higher than in the power-arousal group. Subjects' postmovie T
      responses (T3) depended on premovie T levels: in men, higher premovie T levels
      predicted a greater likelihood of postmovie T increases in the Power Arousal
      condition but not in the other conditions, whereas in women, higher premovie T
      levels tended to be associated with postmovie T decreases in the Power Arousal
      condition but not in the other conditions. These findings suggest that aroused
      affiliation motivation has a specific stimulatory effect on P, whereas aroused
      power motivation has a specific stimulatory effect on T in men, but not in women,
      with high baseline T levels.

PMID- 15555502
TI  - Effects of the menstrual cycle on auditory event-related potentials.
AB  - Gonadal steroids (estradiol and progesterone) can alter neuronal functioning, but
      electrophysiological evidence in women is still sparse. Therefore, the present
      study investigated event-related potentials (ERPs) to neutral stimuli over the
      course of the menstrual cycle. In addition, associations between ERPs and
      salivary estradiol and progesterone concentrations were investigated. Eighteen
      young healthy women were tested at three different phases of their menstrual
      cycle (menses, and follicular and luteal phases). ERPs (i.e., the N1 and P2
      components, reflecting cortical arousal and the orienting response, the N2, P3,
      and the Slow Wave (SW), reflecting controlled processing) were measured using two
      different paradigms. In the luteal phase, early ERPs reflecting the cortical
      arousal response were diminished in the first stimulus block indicating an
      attenuated orienting response. These changes were significantly correlated with
      estradiol as well as progesterone levels. As to the later ERP components, the N2
      latency was shorter during menses compared to the other two phases. No menstrual
      cycle-associated changes were apparent in other late ERP components. In sum, this
      study documents changes in auditory ERPs across the menstrual cycle with the most
      prominent changes occurring during the luteal phase. Future ERP studies therefore
      need to be more attentive to the issue of menstrual phase when studying female
      subjects or female patients.

PMID- 15555503
TI  - Changes along the male reproductive axis in response to social context in a
      gonochoristic gobiid, Zosterisessor ophiocephalus (Teleostei, Gobiidae), with
      alternative mating tactics.
AB  - Sexual selection has given rise, in several taxa, to intrasexual variation in
      male phenotype. While evolutionary studies have provided explanations of the
      adaptive function of this dramatic male phenotypic diversity, the proximate
      control of its expression has still to be completely understood. Several
      observations, primarily from sex-changing species, indicated a major role of
      social interactions in reproductive axis regulation and consequently in the
      expression of alternative male phenotypes. Here we documented changes along the
      male reproductive axis in response to social context in a gonochoristic species,
      the grass goby Zosterisessor ophiocephalus, where fully functional alternative
      male mating tactics appear to be expressed as an ontogenetic gradient. In the
      grass goby, larger and older males dig a nest and perform parental care, while
      smaller males sneak fertilization during territorial male spawning. Territorial
      males are characterized by a higher number of gonadotropin-releasing hormone
      (GnRH) neurons in forebrain preoptic area, smaller testes, larger seminal
      vesicles, and viscous ejaculates that last longer and contain fewer sperm than
      those of sneakers. To experimentally investigate the role of social factors in
      inducing changes along the male reproductive axis, sneakers were tested in two
      different situations: nesting alone or with ripe females. Sneakers that mated and
      performed parental care showed dramatic changes in brain, reproductive apparatus
      morphology, and ejaculate traits. GnRH-immunoreactive cells in forebrain preoptic
      area increased in number, reaching values typical of wild-caught parental males.
      Testes size decreased while seminal vesicle size increased and ejaculates showed
      lower sperm densities. These results were discussed within the framework of the
      social transduction hypothesis, which predicts that social experience should
      mediate, through a cascade of internal processes, shifts between morphs
      throughout life.

PMID- 15555504
TI  - Patterns of cortisol reactivity to laboratory stress.
AB  - Cortisol responses to a laboratory stress protocol were investigated in 82 male
      firefighters. Saliva samples were collected during an adaptation period beginning
      between 9 and 10 am, and then at the end of each of six 10-min trials (a mental
      arithmetic task, an inter-task recovery period, a speech task, and three recovery
      periods). Individual differences in the mean cortisol response to the stress
      tasks were characterized by variation in the direction of the response, as well
      as the size of the response. Neither pre-stress cortisol levels nor responses
      were correlated with cardiovascular and mood responses. Cortisol levels before
      stress task presentation were negatively correlated with recent stress severity.
      Larger mean cortisol responses were associated with lower reports of recent
      stress exposure, lower negative affect scores, and a coping style characterized
      less experience of anger, more control over anger expression, and a tendency to
      screen out threatening information in stressful situations. Thus, increased
      cortisol activity was associated with less recent stress exposure and a more
      adaptive behavioral style than for those whose cortisol levels fell or were
      largely unchanged in response to a laboratory stressor.

PMID- 15555505
TI  - Exogenous vasotocin alters aggression during agonistic exchanges in male Amargosa
      River pupfish (Cyprinodon nevadensis amargosae).
AB  - Pupfishes in the Death Valley region have rapidly differentiated in social
      behaviors since their isolation in a series of desert streams, springs, and
      marshes less than 20,000 years ago. These habitats can show dramatic fluctuations
      in ecological conditions, and pupfish must cope with the changes by plastic
      physiological and behavioral responses. Recently, we showed differences among
      some Death Valley populations in brain expression of arginine vasotocin (AVT). As
      AVT regulates both hydromineral balance and social behaviors in other taxa, these
      population differences may indicate adaptive changes in osmoregulatory and/or
      behavioral processes. To test whether AVT is relevant for behavioral shifts in
      these fish, here we examined how manipulations to the AVT system affect agonistic
      and reproductive behaviors in Amargosa River pupfish (Cyprinodon nevadensis
      amargosae). We administered exogenous AVT (0.1, 1, and 10 microg/g body weight)
      and an AVP V1 receptor antagonist (Manning compound, 2.5 microg/g body weight)
      intraperitoneally to males in mixed-sex groups in the laboratory. We found that
      AVT reduced the initiation of aggressive social interactions with other pupfish
      but had no effect on courtship. The effects of AVT were confirmed in males in the
      wild where AVT (1 microg/g body weight) reduced the aggressive initiation of
      social interactions and decreased aggressive responses to the behavior of other
      males. Combined, these results show that AVT can modulate agonistic behaviors in
      male pupfish and support the idea that variation in AVT activity may underlie
      differences in aggression among Death Valley populations.

PMID- 15555506
TI  - Social motivation is reduced in vasopressin 1b receptor null mice despite normal
      performance in an olfactory discrimination task.
AB  - In this study, we characterized more thoroughly the social behavior of
      vasopressin 1b receptor null (V1bR-/-) mice. We confirmed that V1bR-/- males
      exhibit less social aggression than their wild-type (V1bR+/+) littermates. We
      tested social preference by giving male subjects a choice between pairs of soiled
      or clean bedding. In general, V1bR+/+ mice spent significantly more time engaged
      in chemoinvestigation of these social stimuli than V1bR-/- mice. Male V1bR+/+
      mice preferred female-soiled bedding over male-soiled bedding, male-soiled
      bedding over clean bedding, and female-soiled bedding over clean bedding. In
      contrast, V1bR-/- males failed to exhibit a preference for any bedding. This
      difference in behavior is not explained by an anosmic condition as there were no
      differences between V1bR-/- and V1bR+/+ mice in their abilities to detect a
      cookie buried in clean bedding, or in their ability to perform in an operant
      conditioning task using a fully automated liquid dilution olfactometer. In the
      latter task, male V1bR-/- mice were fully capable of discriminating between male
      and female mouse urine. The latencies to learn this task did not differ between
      the two genotypes. Thus, a V1bR-/- male's ability to differentiate between male
      and female chemosensory cues appears no different than that of a V1bR+/+ male's.
      We propose that the V1bR plays an important role in social motivation, perhaps by
      coupling the processing, integration, and/or interpretation of chemosensory cues
      with the appropriate behavioral response.

PMID- 15555507
TI  - Visual sex discrimination in goldfish: seasonal, sexual, and androgenic
      influences.
AB  - The olfactory signals used by goldfish for sexual and aggressive communication
      have been studied extensively, but little work has addressed the role of other
      sensory modalities in social communication in this species. We therefore
      investigated the role that visual stimuli play in sex discrimination and the
      ability of androgens, which masculinize courtship behavior, to affect behavioral
      responses toward female visual stimuli. We found that males selectively orient
      toward female visual stimuli during the breeding season but not outside it,
      whereas prostaglandin F2-alpha (PGF2alpha)-injected females do not differentially
      approach male and female visual stimuli, even during the breeding season.
      Implanting adult females with testosterone (T) and 11-ketotestosterone (KT),
      however, induced orientation responses toward female visual stimuli similar to
      those observed in males. These results indicate that visual sexual stimuli are
      likely important for reproductive signaling in goldfish, potentially helping
      males identify ovulating females from a distance in a shoal of fish, and that
      androgens can influence mechanisms associated with orientation responses toward
      such stimuli.

PMID- 15555508
TI  - Hormonal correlates of siblicide in Nazca boobies: support for the Challenge
      Hypothesis.
AB  - The androgen hormone testosterone (T) mediates vertebrate aggression in many
      contexts and according to the Challenge Hypothesis is up-regulated during social
      challenges. While originally applied to challenges experienced by breeding
      adults, we show for the first time that T is similarly up-regulated during deadly
      sibling aggression in young birds. When two nestling Nazca boobies hatch, one-
      usually the older chick--virtually always kills the other chick by pushing it
      from the nest. We compared concentrations of T, dehydroepiandrosterone (DHEA; a
      precursor of T), and corticosterone (Cort; a stress hormone) of chicks at various
      stages. T was elevated during fights in both chicks in two-chick broods, but not
      before and after fights, and not in chicks lacking a nest mate. DHEA was elevated
      1 day after hatching and declined with age but appeared not to vary in concert
      with aggression. Cort did not vary across fighting and nonfighting periods. In
      conjunction with an earlier study [Tarlow, E.M., Wikelski, M., Anderson, D.J.,
      2001. Hormonal correlates of siblicide in Galapagos Nazca boobies. Horm. Behav.
      40:14-20], these results indicate that T is temporarily up-regulated around the
      time of fights, as predicted by the Challenge Hypothesis. Our data suggest a
      general role for T during challenges at any time in life, not just during
      breeding.

PMID- 15555509
TI  - Relationships between sex hormones assessed in amniotic fluid, and maternal and
      umbilical cord serum: what is the best source of information to investigate the
      effects of fetal hormonal exposure?
AB  - Levels of testosterone (T) (total and free), androstenedione (A4),
      dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and
      estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies
      (77 male and 79 female fetuses). Samples were obtained from amniotic fluid, 2nd
      and 3rd trimester maternal serum, and umbilical cord serum at birth. During the
      critical period of brain differentiation, at the beginning of the second
      trimester of pregnancy, sex differences in T and A4 were found in amniotic fluid
      and not in maternal serum. This finding adds to the fact that mostly low and
      nonsignificant correlations were found for the different androgenic hormones
      between levels assessed in amniotic fluid and maternal plasma at this particular
      and very sensitive period of fetal brain development. On the other hand, high
      correlations were found for the same hormones between the samples of maternal
      serum in the 2nd and the 3rd trimester. Our data show that, of all available
      sources, amniotic fluid seems to be the best candidate to investigate the effects
      of early fetal androgen exposure.

PMID- 15555510
TI  - Development of prolactin levels in marmoset males: from adult son to first-time
      father.
AB  - Previous studies have found a clear relationship between prolactin (prl) and
      paternal care in various vertebrate taxa. In New World monkeys, it has been
      demonstrated in several species that fathers have high prolactin levels even
      during periods without infant rearing. In this study, we followed the
      reproductive careers of common marmoset males as they transitioned from being an
      adult son within their native family to fathering their own offspring for the
      first time. Specifically, we examined the first experience of elevated prolactin
      levels in marmoset males. Additionally, we investigated the effects of the total
      number of experienced births as well as of age on prolactin levels. Our results
      show that common marmoset males did not experience an increase in prolactin
      secretion after pairing or shortly before birth of their first infants. However,
      prolactin levels rose more than twofold after the birth of their first infants
      and had lowered again 2.5 months after this event. We found no correlation
      between prolactin levels and the number of previous births experienced or age.
      Our study demonstrates that further work about a possible enhancing effect of
      prolactin on paternal care, by means of experimentally reducing hormonal levels,
      should be conducted in common marmosets using first-time fathers before males
      experience the first paternal increase in prolactin levels.

PMID- 15555511
TI  - Exogenous testosterone inhibits several forms of male parental behavior and
      stimulates song in a monogamous songbird: the blue-headed vireo (Vireo
      solitarius).
AB  - Natural variation in circulating testosterone is thought to play a role in
      creating inter- and intraspecific variation in paternal care in birds.
      Experimental elevation of plasma testosterone in males has reduced rates of male
      care in many species. However, a small number of studies suggest that male care
      is not inhibited by testosterone when there appears to be strong selection for
      male care. Both genetic monogamy and male incubation are thought to be the result
      of selection for biparental care, yet the sensitivity of male care to inhibition
      by T had not been examined in a species with both characteristics. Male blue
      headed vireos have been shown to be strictly monogamous and provide extensive
      parental care, including incubation. Males received subcutaneous implants of
      testosterone, flutamide (an anti-androgen), or empty controls. Consistent with
      previous studies, testosterone treatment decreased the relative contribution to
      incubation by males and increased the average duration that the nest was left
      unattended during incubation, relative to control and flutamide treatments. The
      relative and absolute rates of feeding offspring and nest sanitation by T-treated
      males also decreased relative to controls. Flutamide-treated males incubated eggs
      and brooded young more than testosterone-treated males, with control males
      performing at intermediate values. Testosterone-treated males sang more often and
      at higher rates, and flutamide-treated males sang less often, than controls.
      These results demonstrate that even in a strictly monogamous songbird with
      biparental incubation, all forms of paternal care remain sensitive to elevated
      plasma testosterone, suggesting a shift from parental effort to mating effort.

PMID- 15555512
TI  - The endogenous androgen-regulated sialorphin modulates male rat sexual behavior.
AB  - In sexually mature male rats, sialorphin is synthesized under androgenic control
      and its surge endocrine secretion is evoked in response to environmental acute
      stress. These findings led us to suggest that this signaling mediator might play
      a role in physiological and behavioral integration, especially reproduction. The
      present study investigates the effects induced by sialorphin on the male sexual
      behavior pattern. Intact male rats were treated in acute mode, with sialorphin at
      the 0.3, 1, and 3 microg/kg doses, before being paired with receptive female for
      45 min. The data obtained show that sialorphin increased, in a dose-related
      manner, the occurrence of intromissions across the successive ejaculatory
      sequences. The rats treated with the highest 3 microg/kg dose significantly
      ejaculated less often compared to controls; however, 80% of them achieved up to
      three ejaculations. Further analyses of mount bouts for rats achieving three
      ejaculations reveal that there were significant stimulatory effects of
      sialorphin, at all doses, on the frequency of intromissions before ejaculation
      and on the propensity of males to engage in investigatory behavior directed to
      the female during the post-ejaculatory interval. Thus, sialorphin has the ability
      to modulate, at doses related to physiological circulating levels, the male rat
      mating pattern, that is, exerting a dual facilitative or inhibitory dose
      dependent effect on the sexual performance, while stimulating the apparent sexual
      arousal or motivation. These findings led us to speculate that the endogenous
      androgen-regulated sialorphin helps modulate the adaptative balance between
      excitatory and inhibitory mechanisms serving appropriate male rat sexual
      response, depending on the context.

PMID- 15555513
TI  - Effects of melatonin on the behavioral and hormonal responses of red-sided garter
      snakes (Thamnophis sirtalis parietalis) to exogenous corticosterone.
AB  - We investigated possible interactions between melatonin and corticosterone in
      modulating the reproductive behavior of male red-sided garter snakes (Thamnophis
      sirtalis parietalis) following spring emergence. We also examined whether
      melatonin's modulatory actions could be explained by its potential properties as
      a serotonin receptor antagonist. Exogenous corticosterone significantly reduced
      courtship behavior of male snakes in a dose-dependent manner. Melatonin also
      significantly reduced courtship behavior of male garter snakes. Pretreatment with
      melatonin before administering corticosterone treatments further suppressed
      courtship behavior of red-sided garter snakes. These results indicate additive
      inhibitory effects of melatonin and corticosterone in modulating reproductive
      behavior. Snakes receiving ketanserin, a serotonergic type 2A receptor
      antagonist, followed by corticosterone also showed reduced courtship behavior;
      this serotonin receptor antagonist followed by treatment with vehicle did not
      significantly influence courtship behavior of male snakes. Neither melatonin nor
      corticosterone treatments significantly influenced testosterone + 5-alpha
      dihydrotestosterone concentrations of male garter snakes, supporting a direct
      effect of melatonin and corticosterone on courtship behavior that is independent
      of any effect on androgen concentrations. We propose that a serotonin system is
      involved in the modulation of male courtship behavior by melatonin and
      corticosterone. In addition, our data support the hypothesis that melatonin may
      function as a serotonin receptor antagonist. Further research is necessary to
      discern whether the actions of melatonin and corticosterone are converging on the
      same pathway or if their effects on different pathways are having additive
      inhibitory effects on courtship behavior.

PMID- 15555514
TI  - Nonbreeding season pairing behavior and the annual cycle of testosterone in male
      and female downy woodpeckers, Picoides pubescens.
AB  - Studies in birds show that testosterone (T) concentrations vary over the annual
      cycle depending on mating system and life history traits. Socially monogamous
      species show pairing behavior throughout the year and low levels of male-male
      aggression and are underrepresented in these studies, yet the function of
      testosterone could be particularly important for sexual and social interactions
      occurring outside the breeding season. We measured fecal T concentrations over
      the annual cycle and the frequency of interactions between male and female downy
      woodpeckers (Picoides pubescens) from late fall through early spring. We
      validated the fecal assay by collecting blood in conjunction with a subsample of
      our fecal samples: fecal T correlated with circulating levels in the blood. The
      annual peak level of T in males was relatively low and short-lived, similar to
      that of other bird species with low levels of male-male aggression and high
      paternal care. The annual cycle of female T resembled the male pattern, and the
      ratio of male T to female T was close to 1.0. Likewise, the frequency of
      aggression among females was similar to the frequency among males. Overall,
      testosterone levels in both sexes were variable, even in winter. In other bird
      species, sexual behavior during nonbreeding periods correlates with circulating
      levels of T in males. Based on this observation, we tested the hypothesis that T
      in winter was positively related to the frequency of interaction between mated
      downy woodpeckers. The results showed no such relationship. We discuss this
      finding and further relate the annual cycle of T in both males and females to
      behaviors that appear to facilitate mate choice and retention of the pair bond
      during conspecific challenge.

PMID- 15555515
TI  - SPECT-CT for topographic mapping of sentinel lymph nodes prior to gamma probe
      guided biopsy in head and neck squamous cell carcinoma.
AB  - INTRODUCTION: Lymphoscintigraphic planar imaging is a common procedure for
      sentinel lymph node imaging prior to lymph node biopsy, but fails to elucidate
      the specific lymphatic drainage. Composite functional/anatomical imaging (SPECT
      CT) has the potential to enhance topographic orientation and diagnostic
      sensitivity of sentinel lymph node imaging, but has not yet been applied in the
      head and neck region. STUDY DESIGN: A total of 30 patients were investigated.
      Planar imaging was 5 min, 265 x 265, right and left lateral; 500 kilocounts
      (Kcts) and SPECT (GE Millenium VG Hawk Eye 6 degrees/30s. step, 128 x 128, slice
      thickness 4.42 mm). Scans were performed 60 min after intra-mucodermal injection
      of 0.1 ml of 20 MBq 99mTc nanocolloid in patients with squamous cell cancer of
      the head and neck. SPECT studies were analysed by filtered back projection (FBP:
      Hann (0.7) prefiltering, Butterworth (0.5) postfiltering) and reconstruction
      (OSEM: Post Filter Hamming (0.85), 2 Iterations) and independently viewed with
      the co-registered CT image (eNTEGRA Functional Anatomical Fusion Vers 2.0216).
      The results were validated by comparing the results of each method employed in
      all 30 cases and intraoperative gamma probe-guided sentinel lymph node biopsy
      with histological examination in 13 of these patients. RESULTS: The majority of
      patients had more than one sentinel node (mean 1.63, min. 0, max. 4). Seven out
      of the 30 studies demonstrated lymphatic flow to the contralateral side of the
      neck. Forty-nine sentinel nodes were identified by iteratively reconstructed
      SPECT-CT. Thirty-eight out of these 49 could be located in lymphoscintigraphic
      planar imaging, whereas only 24/49 were detected in filtered back projection,
      respectively. In 11 of the 30 cases, a clinically unpredictable pattern of
      lymphatic drainage was observed. No correlation was found between T stage or
      tumour location and the number of sentinel nodes detected. In one out of the 13
      cases, in whom imaging was followed by intraoperative gamma probe-guided biopsy,
      no sentinel node could be detected with the probe in the proximity of the primary
      tumour, although the node was clearly discernible in the reconstructed SPECT-CT.
      CONCLUSION: Composite functional/anatomical imaging (SPECT-CT) is feasible for
      sentinel lymph node detection. It enhances topographic orientation and diagnostic
      sensitivity with more sentinel nodes being detectable than by planar
      lymphoscintigraphy alone. Planar imaging should be accompanied by iterative
      reconstructed SPECT-CT to identify lymph nodes adjacent to the primary lesion.
      Such nodes are easily overlooked by planar lymphoscintigraphy and intraoperative
      gamma probes, as the high activity at the injection site can obscure their
      detection.

PMID- 15555516
TI  - Superficial parotidectomy: technical modifications based on tumour
      characteristics.
AB  - AIM: The purpose of this study was to evaluate the adequacy of partial
      superficial parotidectomy and tumour enucleation in the surgical management of
      patients with pleomorphic adenoma of the parotid. MATERIAL AND METHODS: A total
      of 62 patients were treated for pleomorphic adenoma of the parotid during the
      years 1995-1999; 17 patients were treated with conventional superficial
      parotidectomy, whereas 42 patients were subjected to partial superficial
      parotidectomy. In three patients, tumour size and facial nerve proximity
      essentially resulted in enucleation of the parotid mass. In partial superficial
      parotidectomy, only the tumour-bearing area of the gland parenchyma was excised
      with identification of the main trunk and preservation of the facial nerve
      division that was adjacent to the tumour site with no need for more extensive
      facial nerve dissection. RESULTS: There was no incidence of recurrence or facial
      nerve injury in our group of patients. The incidence of Frey's syndrome was 4.8%.

PMID- 15555517
TI  - Eminectomy and plication of the posterior disc attachment following arthrotomy
      for temporomandibular joint internal derangement.
AB  - AIM: The aim of this study was to assess the success of a single surgical
      procedure (eminectomy and meniscal plication) in patients with internal
      derangement of the temporomandibular joint. PATIENTS: A retrospective survey of
      119 joints (92 patients), that had undergone eminectomy +/- meniscal plication
      for internal derangement of the temporomandibular joint, over a 10 year period,
      was undertaken. METHODS: The same surgeon undertook all surgery and clinical
      evaluation. Assessment of joint pain, noise/click, and mobility were assessed pre
      and post-operatively. Clinical assessment at 24 months postoperatively and
      patient evaluation (average 59 months postoperatively) formed the basis for the
      results. RESULTS: Clinical assessment and patient evaluation revealed an
      improvement in pain (65%), noise (63%) and mobility (71%). The outcome of surgery
      as assessed by the patients and clinicians showed that both have similar
      expectations and evaluations of the results of temporomandibular joint surgery,
      which were reasonably good. Arthrography, which was used as a diagnostic
      technique prior to surgery, was shown to be unreliable with relatively low
      sensitivity and specificity.

PMID- 15555518
TI  - Ablation of temporomandibular joint structures of a pig with a fibre-guided 308
      nm excimer laser light--an in vitro investigation.
AB  - PURPOSE: The present in vitro investigation was carried out to assess the
      efficacy of treatment with 308 nm excimer laser radiation applied to the
      structures of the temporomandibular joint of a pig. Laser parameters suitable to
      ensure adequate clinical efficiency with only minor thermal damage to the
      surrounding tissues were to be determined. MATERIAL AND METHODS: Tissue
      structures of the temporomandibular joint (cortical and cancellous bone,
      cartilage, disc and muscle) were extracted from freshly killed pigs and served as
      specimens. The specimens were embedded in polymethylmethacrylate. The laser light
      was applied after horizontal sectioning and measurement of thickness. The number
      of impulses that were necessary to perforate the specimen was counted and the
      rate of ablation determined. In addition, the irradiated surface was investigated
      histologically and the degree of tissue alteration was evaluated. RESULTS: The
      lowest energy threshold for ablation was found at an energy density of 0.8 J/cm2.
      Depending on the type of tissue, the maximum rate of ablation was evaluated as
      1.7-6.3 microm/pulse. The depth of the thermal alteration to the surrounding
      tissue was about 30-70 microm. CONCLUSION: The guidable 308 nm excimer laser
      light offers a combination of precise tissue ablation with only minimal thermal
      damage to the surrounding tissue.

PMID- 15555519
TI  - Histological investigation of osteoinductive properties of rh-BMP2 in a rat
      calvarial bone defect model.
AB  - INTRODUCTION: Recombinant human bone morphogenetic protein-2 (rh-BMP2) has
      osteoinductive properties. The sequence of osteogenesis induced by rh-BMP2 in a
      rat calvarial bone defect model was evaluated histologically. MATERIAL AND
      METHODS: Atelopeptide type I collagen was selected as the carrier matrix for rh
      BMP2. This collagen was mixed with 50 microg of rh-BMP2 and treated by
      lyophilization to make a suitable form for filling bone defects. Thirty Wistar
      rats (male; 10 weeks old) underwent craniotomy resulting in a round bone defect
      with a diameter of 4 mm. Three weeks after the operation, the defect site was
      exposed to implant collagen with rh-BMP2 in the experimental group and collagen
      only in the control group. Three, 6 and 9 weeks after implantation, calvarial
      specimens were harvested and stained with haematoxylin/eosin. In addition,
      bromodeoxyuridine (BrdU) immunohistochemical staining was performed. RESULTS: In
      the experimental group, marked ossification was found. In contrast, there was no
      tendency towards osteogenesis in the control group, 9 weeks after collagen
      implantation. In BrdU immunohistochemical staining, the number of BrdU-positive
      cells was significantly higher in the experimental group than in the control
      group, and was significantly higher at the periosteal site than at other sites at
      3 and 6 weeks after implantation. CONCLUSIONS: rh-BMP2 exhibited osteoinductive
      properties, and markedly stimulated proliferation of periosteal cells.

PMID- 15555520
TI  - Autologous stem cells (adipose) and fibrin glue used to treat widespread
      traumatic calvarial defects: case report.
AB  - This is a report of a 7-year-old girl suffering from widespread calvarial defects
      after severe head injury with multifragment calvarial fractures, decompressive
      craniectomy for refractory intracranial hypertension and replantation of
      cryopreserved skull fragments. Chronic infection resulted in an unstable skull
      with marked bony defects. Two years after the initial injury the calvarial
      defects were repaired. Due to the limited amount of autologous cancellous bone
      available from the iliac crest, autologous adipose derived stem cells were
      processed simultaneously and applied to the calvarial defects in a single
      operative procedure. The stem cells were kept in place using autologous fibrin
      glue. Mechanical fixation was achieved by two large, resorbable macroporous
      sheets acting as a soft tissue barrier at the same time. The postoperative course
      was uneventful and CT-scans showed new bone formation and near complete calvarial
      continuity three months after the reconstruction.

PMID- 15555521
TI  - Orbital wall reconstruction with bone grafts from the outer cortex of the
      mandible.
AB  - AIM: The purpose of the study was to assess the efficacy of bone grafting from
      the mandibular outer cortex for reconstructing the orbital walls. MATERIAL AND
      METHODS: Bone grafting was performed in 75 patients. The site the transplants
      were harvested from were: A: mental region, B: area posterior to the mental
      foramen, C: ramus region. In order to obtain the appropriate curvature for the
      orbital floor, proper selection of the donor area is required. The bony defect
      size was confirmed pre-operatively from 3D-CT data. Bone, characteristically 2-3
      mm thick, was harvested from each area and grafted into the blow-out fractures.
      RESULTS: Out of the 75 patients 13 cases underwent reconstruction using
      mandibular outer cortex bone from area A, 8 from area B, and 54 from area C. The
      maximum size available for harvest from area C was 7 x 4 cm; material from this
      area could also be used for the repair of both medial and inferior orbital wall
      defects if necessary. CONCLUSION: Bone harvest from the mandible affords several
      advantages including (1) ease of harvest, (2) ease of trimming, (3) appropriate
      size and curvature, (4) absence of functional disability, (5) no secondary
      deformity, (6) no visible scars, (7) post-operative immobilization not necessary,
      (8) absence of post-operative difficulties with respect to breathing and walking
      and (9) major complications are rare.

PMID- 15555522
TI  - Le Fort I osteotomy using an ultrasonic bone curette to fracture the pterygoid
      plates.
AB  - PURPOSE: The purpose of this study was to evaluate the advantageous use of an
      ultrasonic bone curette and to assess the mobilization of the pterygoid process
      after a Le Fort I osteotomy. MATERIAL AND METHODS: 14 Japanese adults (ranging in
      age from 17 to 30 years, mean 22.4) with jaw deformities diagnosed as mandibular
      prognathism or bimaxillary asymmetry underwent Le Fort I osteotomy with bilateral
      sagittal split ramus osteotomy or intraoral vertical ramus osteotomy. During the
      Le Fort I osteotomy, the Sonopet UST-2000 ultrasonic bone curette was used to
      fracture the pterygoid process slightly above the level of the maxillary
      osteotomy without damaging the descending palatine artery or other blood vessels
      and nerves. After surgery, the pterygoid process osteotomy and its mobility were
      evaluated from three-dimensional computed tomographic images. RESULTS: In all
      cases, the mobility of the pterygoid process could be achieved by using the
      device safely with minimal bleeding and no notable complications. The maxillary
      segment could be fixed in an ideal position and in all 14 cases, an ideal profile
      was achieved. CONCLUSION: Ultrasonic bone curette offers a safe procedure for
      performing pterygoid process fractures without damaging the surrounding tissue
      such as the descending palatine artery.

PMID- 15555523
TI  - Improving the iliac crest donor site by plate insertion after harvesting
      vascularized bone.
AB  - The iliac crest is among the most frequent sites for free vascularized bone
      donation. However, donor site morbidity is often marked with persistent pain,
      abnormal sensation, abdominal herniation, musculoskeletal imbalance and a
      disfigured appearance. The authors present a technique of reconstructing the bony
      gap after iliac crest harvest by inserting a metal plate. Apart from restoration
      of the iliac contour after skin closure, the plate enables fixation of the
      transected abdominal wall muscles. This results in less postoperative pain and
      shorter rehabilitation, as well as an improved musculoskeletal balance and a
      reduced risk of abdominal wall herniation.

PMID- 15555524
TI  - Craniofacial hyperostoses in Proteus syndrome -- a case report.
AB  - OBJECTIVE: Description of a patient with a rare syndrome leading to the partial
      overgrowth of craniofacial bones. CASE REPORT: In a 17-year-old female patient
      with severe hyperostoses of the craniofacial bones asymmetric overgrowth of the
      right upper and left lower limbs, linear hyperpigmentation of the right arm and a
      history of regional lipomatosis were found. These manifestations were suggestive
      of Proteus syndrome. The management of the craniofacial involvement is described
      and a literature overview presented. CONCLUSION: Proteus syndrome is a rare
      overgrowth syndrome probably related to a somatic mutation that involves
      craniofacial structures in about 30% of patients. Early diagnosis is required for
      adequate interdisciplinary treatment.

PMID- 15555525
TI  - How genetic is school myopia?
AB  - Myopia is of diverse aetiology. A small proportion of myopia is clearly familial,
      generally early in onset and of high level, with defined chromosomal
      localisations and in some cases, causal genetic mutations. However, in
      economically developed societies, most myopia appears during childhood,
      particularly during the school years. The chromosomal localisations characterised
      so far for high familial myopia do not seem to be relevant to school myopia.
      Family correlations in refractive error and axial length are consistent with a
      genetic contribution to variations in school myopia, but potentially confound
      shared genes and shared environments. High heritability values are obtained from
      twin studies, but rest on contestable assumptions, and require further critical
      analysis, particularly in view of the low heritability values obtained from
      parent-offspring correlations where there has been rapid environmental change
      between generations. Since heritability is a population-specific parameter, the
      values obtained on twins cannot be extrapolated to define the genetic
      contribution to variation in the general population. In addition, high
      heritability sets no limit to the potential for environmentally induced change.
      There is in fact strong evidence for rapid, environmentally induced change in the
      prevalence of myopia, associated with increased education and urbanisation. These
      environmental impacts have been found in all major branches of the human family,
      defined in modern molecular terms, with the exception of the Pacific Islanders,
      where the evidence is too limited to draw conclusions. The idea that populations
      of East Asian origin have an intrinsically higher prevalence of myopia is not
      supported by the very low prevalence reported for them in rural areas, and by the
      high prevalence of myopia reported for Indians in Singapore. A propensity to
      develop myopia in "myopigenic" environments thus appears to be a common human
      characteristic. Overall, while there may be a small genetic contribution to
      school myopia, detectable under conditions of low environmental variation,
      environmental change appears to be the major factor increasing the prevalence of
      myopia around the world. There is, moreover, little evidence to support the idea
      that individuals or populations differ in their susceptibility to environmental
      risk factors.

PMID- 15555526
TI  - The optic nerve head as a biomechanical structure: a new paradigm for
      understanding the role of IOP-related stress and strain in the pathophysiology of
      glaucomatous optic nerve head damage.
AB  - We propose here a conceptual framework for understanding the optic nerve head
      (ONH) as a biomechanical structure. Basic principles of biomechanical engineering
      are used to propose a central role for intraocular pressure (IOP)-related stress
      and strain in the physiology of ONH aging and the pathophysiology of glaucomatous
      damage. Our paradigm suggests that IOP-related stress and strain (1) are
      substantial within the load-bearing connective tissues of the ONH even at low
      levels of IOP and (2) underlie both ONH aging and the two central
      pathophysiologies of glaucomatous damage--mechanical failure of the connective
      tissues of the lamina cribrosa, scleral canal wall, and peripapillary sclera, and
      axonal compromise within the lamina cribrosa by a variety of mechanisms. Modeling
      the ONH as a biomechanical structure generates a group of testable hypotheses
      regarding the central mechanisms of glaucomatous damage and provides a logic for
      classifying the principal components of the susceptibility of an individual ONH
      to a given level of IOP.

PMID- 15555527
TI  - The role of Muller cells in fibrocontractive retinal disorders.
AB  - Despite advances in surgical management of fibrocontractive retinal disorders,
      proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy
      (PDR) remain major causes of blindness and there is still considerable
      uncertainty about the origins and roles of the cell types involved. Muller cells
      and cells identified as retinal glia are consistently identified in epiretinal
      tissues from both types of disorders. However, their abundance relative to total
      cell populations is generally low, leaving their role in these disorders
      uncertain. Studies of Muller cell biology using tissue culture and animal models
      provide evidence of the remarkable capacity of this cell type for graded
      responses to environmental insult, the capacity to proliferate, translocate from
      the retina and alter phenotype and thus, functional characteristics. This review
      considers the potential roles of Muller cells in fibrocontractive retinal
      disorders and, in particular, evidence that Muller cells function as an effector
      cell type in traction retinal detachment associated with PVR and PDR.

PMID- 15555528
TI  - The role of omega-3 long-chain polyunsaturated fatty acids in health and disease
      of the retina.
AB  - In this work we advance the hypothesis that omega-3 (omega-3) long-chain
      polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic
      actions contributing to a number of anti-angiogenic and neuroprotective
      mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes
      and attenuate effects of environmental exposures that activate molecules
      implicated in pathogenesis of vasoproliferative and neurodegenerative retinal
      diseases. These processes and exposures include ischemia, chronic light exposure,
      oxidative stress, inflammation, cellular signaling mechanisms, and aging. A
      number of bioactive molecules within the retina affect, and are effected by such
      conditions. These molecules operate within complex systems and include compounds
      classified as eicosanoids, angiogenic factors, matrix metalloproteinases,
      reactive oxygen species, cyclic nucleotides, neurotransmitters and
      neuromodulators, pro-inflammatory and immunoregulatory cytokines, and
      inflammatory phospholipids. We discuss the relationship of LCPUFAs with these
      bioactivators and bioactive compounds in the context of three blinding retinal
      diseases of public health significance that exhibit both vascular and neural
      pathology. How is omega-3 LCPUFA status related to retinal structure and
      function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a
      major structural lipid of retinal photoreceptor outer segment membranes.
      Biophysical and biochemical properties of DHA may affect photoreceptor membrane
      function by altering permeability, fluidity, thickness, and lipid phase
      properties. Tissue DHA status affects retinal cell signaling mechanisms involved
      in phototransduction. DHA may operate in signaling cascades to enhance activation
      of membrane-bound retinal proteins and may also be involved in rhodopsin
      regeneration. Tissue DHA insufficiency is associated with alterations in retinal
      function. Visual processing deficits have been ameliorated with DHA
      supplementation in some cases. What evidence exists to suggest that LCPUFAs
      modulate factors and processes implicated in diseases of the vascular and neural
      retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary
      intake. Certain LCPUFAs are selectively accreted and efficiently conserved within
      the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal
      cell gene expression, cellular differentiation, and cellular survival. DHA
      activates a number of nuclear hormone receptors that operate as transcription
      factors for molecules that modulate reduction-oxidation-sensitive and
      proinflammatory genes; these include the peroxisome proliferator-activated
      receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR
      alpha, this action is thought to prevent endothelial cell dysfunction and
      vascular remodeling through inhibition of: vascular smooth muscle cell
      proliferation, inducible nitric oxide synthase production, interleukin-1 induced
      cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production.
      Research on model systems demonstrates that omega-3 LCPUFAs also have the
      capacity to affect production and activation of angiogenic growth factors,
      arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs.
      Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a
      family of eicosanoids that have the potential to affect AA-derived eicosanoids
      implicated in abnormal retinal neovascularization, vascular permeability, and
      inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific
      tyrosine kinase receptor activation and expression. VEGF plays an essential role
      in induction of: endothelial cell migration and proliferation, microvascular
      permeability, endothelial cell release of metalloproteinases and interstitial
      collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor
      down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa
      B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2
      expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase.
      All four factors are associated with vascular instability. COX-2 drives
      conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our
      general conclusion is that there is consistent evidence to suggest that omega-3
      LCPUFAs may act in a protective role against ischemia-, light-, oxygen-,
      inflammatory-, and age-associated pathology of the vascular and neural retina.

PMID- 15555529
TI  - Essential role for the p40 subunit of interleukin-12 in neutrophil-mediated early
      host defense against pulmonary infection with Streptococcus pneumoniae:
      involvement of interferon-gamma.
AB  - Interleukin (IL)-12 is a critical cytokine in the T helper (Th)1 response and
      host defense against intracellular microorganisms, while its role in host
      resistance to extracellular bacteria remains elusive. In the present study, we
      elucidated the role of IL-12 in the early-phase host defense against acute
      pulmonary infection with Streptococcus pneumoniae, a typical extracellular
      bacterium, using IL-12p40 gene-disrupted (IL-12p40KO) mice. IL-12p40KO mice were
      highly susceptible to S. pneumoniae infection, as indicated by the shortened
      survival time, which was completely restored by the replacement therapy with
      recombinant (r) IL-12, and increased bacterial counts in the lung. In these mice,
      recruitment of neutrophils in the lung was significantly attenuated when compared
      to that in wild-type (WT) mice, which correlated well with the reduced production
      of macrophage inflammatory protein (MIP-2) and tumor necrosis factor (TNF)-alpha
      in the infected tissues at the early phase of infection. In vitro synthesis of
      both cytokines by S. pneumoniae-stimulated lung leukocytes was significantly
      lower in IL-12p40KO mice than in WT mice, and addition of rIL-12 or interferon
      (IFN)-gamma restored the reduced production of MIP-2 and TNF-alpha in IL-12p40KO
      mice. Neutralizing anti-IFN-gamma monoclonal antibody (mAb) significantly
      decreased the effect of rIL-12. Anti-IFN-gamma mAb shortened the survival time of
      infected mice and reduced the recruitment of neutrophils and production of MIP-2
      and TNF-alpha in the lungs. Our results indicated that IL-12p40 plays a critical
      role in the early-phase host defense against S. pneumoniae infection by promoting
      the recruitment of neutrophils to the infected tissues.

PMID- 15555531
TI  - Involvement of peptidorhamnomannan in the interaction of Pseudallescheria boydii
      and HEp2 cells.
AB  - Pseudallescheria boydii is an emerging fungal pathogen that has a worldwide
      distribution. Virulence mechanisms of P. boydii are largely unknown. We studied
      the interaction between P. boydii and HEp2 cells and demonstrated that conidia of
      P. boydii attached to, and were ingested by, HEp2 cells in a time-dependent
      process. After 2 h of interaction, the conidia produced a germ-tube like
      projection, which was able to penetrate the epithelial cell membrane. Recently,
      our group characterized a peptidorhamnomannan (PRM) antigen on the cell surface
      of P. boydii. In order to better understand the role played by this surface
      glycoconjugate during cell adhesion and endocytosis, inhibition assays were
      performed using intact PRM and anti-PRM polyclonal antibody. When HEp2 cells were
      pre-treated with whole PRM molecule, the adhesion and endocytic indices were,
      respectively, 50% and 60% lower than in non-treated epithelial cells. Moreover,
      when the conidial cells were pre-incubated with anti-PRM antibodies, the
      adherence and endocytosis processes were inhibited in a dose-dependent manner. As
      PRM influenced the conidia P. boydii-HEp2 cell interaction, we also performed
      inhibition assays in order to observe which PRM moieties could be involved in
      this process. Treatment of PRM with proteinase K promoted a slight inhibition of
      adhesion. However, the de-O-glycosylated PRM molecule as well as the
      monosaccharide mannose was able to efficiently inhibit the adhesion and endocytic
      processes. In addition, our results indicate for the first time that P. boydii
      PRM binds to a polypeptide of 25 kDa on the HEp2 cell surface.

PMID- 15555530
TI  - Immune response to a major Trypanosoma cruzi antigen, cruzipain, is
      differentially modulated in C57BL/6 and BALB/c mice.
AB  - BALB/c mice immunized with cruzipain, a major Trypanosoma cruzi antigen, produce
      specific and autoreactive immune responses against heart myosin, associated with
      cardiac functional and structural abnormalities. Preferential activation of the
      Th2 phenotype and an increase in cell populations expressing CD19+, Mac-1+ and Gr
      1+ markers were found in the spleens of these mice. The aim of the present study
      was to investigate whether cardiac autoimmunity could be induced by cruzipain
      immunization of C57BL/6 mice and to compare the immune response elicited with
      that of BALB/c mice. We demonstrate that immune C57BL/6 splenocytes, re
      stimulated in vitro with cruzipain, produced high levels of IFNgamma and low
      levels of IL-4 compatible with a Th1 profile. In contrast to BALB/c mice, spleens
      from cruzipain immune C57BL/6 mice revealed no significant changes in the number
      of cells presenting CD19+, Mac-1+ and Gr-1+ markers. An increased secretion of
      TGFbeta and a greater number of CD4+ TGFbeta+ cells were found in immune C57BL/6
      but not in BALB/c mice. These findings were associated with the lack of
      autoreactive response against heart myosin and a myosin- or cruzipain-derived
      peptide. Thus, the differential immune response elicited in C57BL/6 and BALB/c
      mice upon cruzipain immunization is implicated in the resistance or pathogenesis
      of experimental Chagas' disease.

PMID- 15555532
TI  - IL-1 receptor-associated kinase 1 mediates protection against Staphylococcus
      aureus infection.
AB  - The interleukin-1 receptor-associated kinase-1 (IRAK-1) mediates signal
      transduction from Toll-like/IL-1/IL-18 receptors. Though a critical protective
      role against Staphylococcus aureus infection has been previously attributed to
      myeloid differentiation factor 88 (MyD88) and IRAK-4, both also involved in
      TLR/IL-1/IL-18 signaling, the role of IRAK-1 is unknown. IRAK-1-deficient (IRAK-1
      /-) and wild-type mice were inoculated i.v. with 2 x 10(7) or 1 x 10(6) S. aureus
      per mouse to evaluate the role of IRAK-1 in S. aureus sepsis. Since IRAK-1
      transduces IL-1R signals, IL-1R-/- mice were also included in experiments. IRAK-1
      /- mice are susceptible to a high dose of S. aureus compared to wild-type
      controls. In contrast to the high mortality and extensive weight loss seen in IL
      1R-deficient mice in response to 1 x 10(6) S. aureus, IRAK-1-/- mice are
      resistant to this low dose of S. aureus. Thus IRAK-1 plays an important role in
      the host response to staphylococcal sepsis.

PMID- 15555533
TI  - Plasma interleukin-18 is associated with viral load and disease progression in
      HIV-1-infected patients.
AB  - Recent studies demonstrate persistent elevation of interleukin-18 (IL-18)
      concentration in human immunodeficiency virus type 1 (HIV-1)-infected patients.
      Due to pleiotropic action of IL-18 on the immune system, dysregulation of its
      synthesis may lead to inappropriate immune activation. The aim of this study was
      to determine possible correlation between IL-18 levels and the natural stages of
      HIV-1 infection. IL-18 plasma concentrations were determined in 42 patients in
      different stages of an HIV-1 infection and in 15 healthy controls. HIV infection
      resulted in a more than fourfold increase of plasma IL-18 concentration compared
      to healthy individuals (865 +/- 87 vs. 206 +/- 32 pg/ml, P < 0.001). Moreover, a
      positive correlation between plasma IL-18 concentration and HIV viral load was
      found (r = 0.44, P < 0.01). Further analysis showed marked elevation of IL-18
      levels in late-stage symptomatic patients. Plasma IL-18 concentrations in
      patients receiving high-activity antiretroviral treatment (HAART) were
      significantly lower than in those not undergoing antiretroviral treatment.
      Individuals who did not reach viral suppression showed higher IL-18 plasma
      concentration than the group with achieved viral suppression. Excessive
      production of IL-18 observed in our study may promote viral replication and
      disease progression in advanced, especially late-stage HIV-infected patients.
      Furthermore, reduction of IL-18 concentration can be an important step in HAART
      related immune restoration.

PMID- 15555534
TI  - Salmonella carrier state in chicken: comparison of expression of immune response
      genes between susceptible and resistant animals.
AB  - Asymptomatic Salmonella enterica serovar Enteritidis carrier state in poultry has
      serious consequences on food safety and public health due to the risks of food
      poisoning following consumption of contaminated products. An understanding the
      mechanisms of persistence of Salmonella in the digestive tract of chicken can be
      achieved by a better knowledge of the defects in the control of infection in
      susceptible versus resistant animals. The gene expression of innate immune
      response factors including anti-microbial molecules, inflammatory and anti
      infectious cytokines was studied in the caecal lymphoid tissue associated with
      the carrier state. Expression levels of these genes were assessed by real-time
      PCR and were compared in two inbred lines of chickens differing in resistance to
      the carrier state following oral inoculation of S. enterica serovar Enteritidis
      at 1 week of age. No correlation was observed between resistance/susceptibility
      to caecal carrier state and level of interleukin (IL)-1beta, IL-8, IL-18,
      inducible NO synthase (iNOS) and natural resistance associated macrophage protein
      1 (NRAMP1). A high baseline level of defensin gene expression was recorded in
      young animals from the susceptible line. In contrast, a significantly low
      expression of interferon-gamma (IFN-gamma) gene was observed in these susceptible
      infected animals in comparison to resistant ones and healthy counterparts. IFN
      gamma expression level represents a valuable indication of immunodeficiency
      associated with persistence of Salmonella in the chicken digestive tract, and IFN
      gamma thus represents a factor to consider in the development of prophylactic
      measures for the reduction of Salmonella carrier state.

PMID- 15555535
TI  - Reduction in adhesiveness to extracellular matrix components, modulation of
      adhesion molecules and in vivo migration of murine macrophages infected with
      Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular parasite, able to disseminate into
      deep tissues and cross biological barriers, reaching immunoprivileged sites such
      as the brain and retina. In order to investigate whether the parasite uses
      leukocyte trafficking to disseminate throughout the host, the adhesive potential
      to extracellular matrix components, the expression of adhesion molecules and the
      in vivo migration of murine macrophages infected with RH strain of T. gondii were
      investigated. Cellular adhesion to fibronectin, laminin and collagen IV decreased
      after 24 h of T. gondii infection. However, the decrease in adhesion of infected
      macrophages observed at early infection was reversed after 48 h. Moreover,
      decreased adhesion was dependent on active penetration, since heat-killed
      parasites were unable to reproduce it. Expression of integrins alphaL, alpha4 and
      alpha5 chains was downmodulated early postinfection, but a progressive regain of
      expression was observed after 12 h of infection. Expression of beta2, alphav and
      alpha4 integrins by peritoneal macrophages at late infection was also gradually
      reestablished. The assessment of in vivo migration of infected macrophages
      labeled with the fluorescent dye 5-chloromethylfluorescein diacetate showed a 48
      h delay in migration to cervical lymph nodes when compared to LPS pre-stimulated
      macrophages. Furthermore, cells that migrate to distal lymph nodes were loaded
      with live parasites. Taken together, these results provide insights about T.
      gondii escape from the host immune response, placing the macrophage as a "Trojan
      horse", contributing to parasite dissemination and access to immunoprivileged
      sites.

PMID- 15555536
TI  - Detection and partial characterisation of two antibacterial factors from the
      excretions/secretions of the medicinal maggot Lucilia sericata and their activity
      against methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Maggot therapy is a simple and highly successful method for cleansing infected
      and necrotic wounds. The use of maggots has become increasingly important in the
      treatment of non-healing wounds, particularly those infected with the multidrug
      resistant pathogen, methicillin-resistant Staphylococcus aureus (MRSA). The
      increasing challenge concerning the treatment of MRSA infections and the recent
      finding of vancomycin-resistant strains of MRSA have elicited the search for
      novel antibacterial compounds and, in particular, investigations into the potent
      antibacterial mechanism(s) behind maggot therapy. In this study, we report that
      excretions/secretions (ES) from the blowfly, Lucilia sericata, exhibit potent,
      thermally stable, protease resistant antibacterial activity against MRSA in
      vitro. We describe the initial characterisation of two antibacterial factors from
      native ES of L. sericata. A small, <500 Da factor with significant antibacterial
      activity against MRSA was partially isolated using ultrafiltration techniques.
      The potent activity of this factor was comparable to that of native
      excretions/secretions. A larger, 0.5-3-kDa factor with significant activity
      against S. aureus was also partially characterised.

PMID- 15555537
TI  - Oral immunization of mice with Japanese encephalitis virus envelope protein
      synthesized in Escherichia coli induces anti-viral antibodies.
AB  - In order to evaluate the possibility of developing an oral vaccine against
      Japanese encephalitis virus (JEV), mice were fed with recombinant JEV envelope
      (E) protein synthesized in Escherichia coli. The protein was administered orally
      to mice with or without an immunostimulatory cytosine-phosphate-guanosine (CpG)
      motif containing synthetic oligodeoxynucleotide (ODN) as an adjuvant. The
      immunized mice made high-titered anti-E and anti-JEV antibodies. Mice immunized
      with JEV E protein along with the ODN adjuvant produced higher antibody titers
      and these were predominantly IgG2a type. These antibodies, however, failed to
      neutralize JEV activity in vitro, and the immunization did not protect the mice
      against lethal JEV challenge. Splenocytes from the immunized mice secreted large
      amounts of interferon (IFN)-gamma and showed proliferation in the presence of JEV
      E protein. Our results indicate that JEV E protein delivered orally to mice
      together with ODN generated both humoral and cellular immune responses to JEV,
      and these were of the Th1 type.

PMID- 15555538
TI  - Reduced clearance of respiratory syncytial virus infection in a preterm lamb
      model.
AB  - Respiratory syncytial virus (RSV) causes significant respiratory disease in
      children worldwide. For the study of severe RSV disease seen in preterm infants,
      a suitable animal model is lacking. The novel hypothesis of this study was that
      preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous
      pneumovirus with ruminant host specificity, and that there would be age-dependent
      differences in select RSV disease parameters. During RSV infection, preterm lambs
      had elevated temperatures and respiration rates with mild anorexia and cough
      compared to controls. Gross lesions included multifocal consolidation and
      atelectasis with foci of hyperinflation. Microscopic lesions included multifocal
      alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the
      RSV antigen to all layers of bronchiolar epithelium from a few basal cells to
      numerous sloughing epithelia. A few mononuclear cells were also immunoreactive.
      To assess for age-dependent differences in RSV infection, neonatal lambs were
      infected similarly to the preterm lambs or with a high-titer viral inoculum.
      Using morphometry at day 7 of infection, preterm lambs had significantly more
      cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation
      (P <0.05) than either group of neonatal lambs. This work suggests that perinatal
      RSV clearance is age-dependent, which may explain the severity of RSV infection
      in preterm infants. The preterm lamb model is useful for assessing age-dependent
      mechanisms of severe RSV infection.

PMID- 15555539
TI  - Genetic diversity in clinical isolates of Mycobacterium avium complex from Guinea
      Bissau, West Africa.
AB  - Isolates of Mycobacterium avium complex (MAC) were cultured from sputum samples
      obtained from patients in Guinea-Bissau, West Africa. Twenty-eight isolates
      hybridising with MAC probe (AccuProbe) were further characterised by different
      molecular techniques: hybridisation with species-specific probes (AccuProbe) for
      M. avium and M. intracellulare, partial sequencing of 16S rRNA gene and PCR
      detection of the DT1-DT6 sequences and the macrophage-induced gene (mig). Only
      one of the 28 isolates reacted with the M. avium probe and four with the M.
      intracellulare probe. Two isolates expressed the DT1 sequence, and three the DT6.
      The mig was detected in 18 (64%) of the isolates. Sequencing of 16S rRNA had the
      greatest discriminative power of the typing methods applied, without strong
      correlation with any other technique. Clinical MAC isolates from Guinea-Bissau
      demonstrated a wide genetic diversity among the members of M. avium complex that
      might reflect on biotope variation.

PMID- 15555540
TI  - Macrophage inflammatory protein-2, neutrophil recruitment and bacterial
      persistence in an experimental mouse model of urinary tract infection.
AB  - This study analyzed macrophage inflammatory protein-2 (MIP-2) production and
      neutrophil recruitment in urinary tract in response to Pseudomonas aeruginosa in
      an ascending model of urinary tract infection (UTI) in mice. Both planktonic and
      biofilm cells of P. aeruginosa were used for inducing UTI in mice. MIP-2 levels
      determined in urine, bladder and kidney showed maximum MIP-2 production 6 h
      postinfection, which correlated with neutrophil recruitment. Biofilm cells showed
      significantly more MIP-2 production and neutrophil recruitment. However, no
      correlation between bacterial numbers and neutrophil recruitment was observed in
      urine and kidney tissue. The role of MIP-2 and neutrophils in relation to the
      persistence of P. aeruginosa in the urinary tract of mice is discussed.

PMID- 15555541
TI  - The role of TRAF6 in signal transduction and the immune response.
AB  - Signals from the IL-1 receptor (IL-1R)/Toll-like receptor (TLR) family and TNF
      receptor (TNFR) superfamily are critical for regulating the function of antigen
      presenting cells such as dendritic cells (DCs). It has been revealed that TNF
      receptor-associated factor 6 (TRAF6), a signaling adapter molecule common to the
      IL-1R/TLR family and TNFR superfamily, is important not only for DC maturation,
      cytokine production, and T cell stimulatory capacity of DCs in response to TLR
      ligands (e.g. lipopolysaccharide) or CD40 ligand, but also for the homeostasis of
      splenic DC subsets.

PMID- 15555542
TI  - Artemisinins: activities and actions.
AB  - Multidrug-resistant malaria caused by Plasmodium falciparum has severely limited
      treatment options over recent years. Artemisinins are still effective for
      treating uncomplicated as well as severe malaria, because resistance is not yet
      clinically apparent. This article reviews some clinically useful properties of
      artemisinins and how they might work.

PMID- 15555543
TI  - The tumor protein D52 family: many pieces, many puzzles.
AB  - Tumor protein D52-like proteins are small coiled-coil motif bearing proteins
      which are conserved from lower organisms to human. The founding member of the
      family, human D52, has principally attracted research interest due to its
      frequent overexpression in cancer, often in association with D52 gene
      amplification. This review summarises published literature concerning this
      protein family since their discovery, which is highlighting an increasing
      diversity of functions for D52-like proteins. This in turn highlights a need for
      more comparative functional analyses, to determine which functions are conserved
      and which may be isoform-specific. This knowledge will be crucial for any future
      manipulation of D52 function in human disease, including cancer.

PMID- 15555544
TI  - Effects of COX-2 inhibitors on ROS produced by Chlamydia pneumoniae-primed human
      promonocytic cells (THP-1).
AB  - Chronic inflammation through foam cells and macrophages is important in
      atherosclerosis development, and can be considered as therapeutic targets.
      Cyclooxygenase and NADPH-oxidase were expressed within atherosclerotic lesions.
      Reactive oxygen species produced by NADPH oxidase were found to trigger the
      cyclooxygenase-2 expression. The effects of preferential COX-2 inhibitors on ROS
      produced by Chlamydia-primed human monocytes (THP-1 cells) were evaluated by
      fluorescence, chemiluminescence, oxymetry, and EPR spin trapping. Fluorescence
      assays showed an increased production of ROS with Chlamydia versus cells primed
      by 10(-8)M PMA. COX-2 inhibitors inhibited in a dose-dependent manner the luminol
      enhanced CL while ibuprofen and diclofenac increased the chemiluminescence
      response. By EPR spin trapping, COX-2 inhibitors, ibuprofen, and diclofenac,
      exhibited a dose-dependent inhibiting effect (10 and 100muM) on the EPR signal
      appearance. Our cell model combining EPR, chemiluminescence, and oxymetry
      appeared relevant to study the modulating effects of preferential COX-2
      inhibitors on the cell oxidant activity and chronic inflammatory diseases.

PMID- 15555545
TI  - Tumor size-independence of telomere length indicates an aggressive feature of
      HCC.
AB  - Using quantitative fluorescence in situ hybridization (Q-FISH), the average
      telomere length of hepatoma cells was assessed by the average telomeric signal
      intensity of cancer cells relative to that of stromal cells. We demonstrated
      first the applicability of Q-FISH for tissue sections by comparing Q-FISH and
      Southern blotting results. Tumors less than 50mm in diameter and with a relative
      telomeric intensity of less than 0.6 were categorized as group A and the
      remainder as group B. In group A, the telomere length correlated negatively with
      tumor size, whereas in group B there was no correlation. Compared with the group
      A tumors, the group B tumors were of significantly more advanced stage, showed
      higher telomerase and proliferative activities, and exhibited less differentiated
      histology. Therefore, we considered that a lack of correlation between telomere
      length and tumor size, namely, size-independence of telomere length, is
      associated with unfavorable clinicopathological features of hepatocellular
      carcinomas.

PMID- 15555546
TI  - Snail regulates p21(WAF/CIP1) expression in cooperation with E2A and Twist.
AB  - Snail, a zinc-finger transcriptional repressor, is essential for mesoderm and
      neural crest cell formation and epithelial-mesenchymal transition. The basic
      helix-loop-helix transcription factors E2A and Twist have been linked with Snail
      during embryonic development. In this study, we examined the role of Snail in
      cellular differentiation through regulation of p21(WAF/CIP1) expression. A
      reporter assay with the p21 promoter demonstrated that Snail inhibited expression
      of p21 induced by E2A. Co-expression of Snail with Twist showed additive
      inhibitory effects. Deletion mutants of the p21 promoter revealed that sequences
      between -270 and -264, which formed a complex with unidentified nuclear
      factor(s), were critical for E2A and Snail function. The E2A-dependent expression
      of the endogenous p21 gene was also inhibited by Snail.

PMID- 15555547
TI  - Cloning and characterization of a novel human zinc finger gene, hKid3, from a
      C2H2-ZNF enriched human embryonic cDNA library.
AB  - To investigate the zinc finger genes involved in human embryonic development, we
      constructed a C(2)H(2)-ZNF enriched human embryonic cDNA library, from which a
      novel human gene named hKid3 was identified. The hKid3 cDNA encodes a 554 amino
      acid protein with an amino-terminal KRAB domain and 11 carboxyl-terminal C(2)H(2)
      zinc finger motifs. Northern blot analysis indicates that two hKid3 transcripts
      of 6 and 8.5kb express in human fetal brain and kidney. The 6kb transcript can
      also be detected in human adult brain, heart, and skeletal muscle while the 8.5kb
      transcript appears to be embryo-specific. GFP-fused hKid3 protein is localized to
      nuclei and the ZF domain is necessary and sufficient for nuclear localization. To
      explore the DNA-binding specificity of hKid3, an oligonucleotide library was
      selected by GST fusion protein of hKid3 ZF domain, and the consensus core
      sequence 5'-CCAC-3' was evaluated by competitive electrophoretic mobility shift
      assay. Moreover, The KRAB domain of hKid3 exhibits transcription repressor
      activity when tested in GAL4 fusion protein assay. These results indicate that
      hKid3 may function as a transcription repressor with regulated expression pattern
      during human development of brain and kidney.

PMID- 15555548
TI  - Enhanced TRAIL sensitivity by E1A expression in human cancer and normal cell
      lines: inhibition by adenovirus E1B19K and E3 proteins.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily
      of cytokines that induces apoptosis in a variety of cancer cells, but not in
      normal cells. However, more and more tumor cells remain resistant to TRAIL, which
      limited its application for cancer therapy. Expression of the adenovirus serotype
      5 (Ad5) E1A sensitizes tumor cells to apoptosis by TNF-alpha, Fas-ligand, and
      TRAIL. Here we asked whether E1A overcomes this resistance and enhances TRAIL
      induced apoptosis in the tumor cells. Our results revealed that the tumor cell
      lines, HeLa and HepG2, with infection by Ad-E1A, were highly sensitive to TRAIL
      induced apoptosis. Importantly, we found that in normal primary human lung
      fibroblast cells (HLF) TRAIL is capable of inducing apoptosis in combination with
      E1A as efficiently as in some tumor cell lines. The adenovirus type 5 encoding
      proteins, E1B19K and E3 gene products, have been shown to inhibit E1A and TRAIL
      induced apoptosis of HLF cells by using the recombinant adenovirus AdDeltaE1B55K,
      with mutation of E1B55K, containing E1B19K and complete E3 region. Further
      results demonstrated that the expression of DR5 and TRAIL was down-regulated in
      the AdDeltaE1B55K co-infected HLF cells. These findings suggest that TRAIL may
      play an important role in limiting virus infections and the ability of adenovirus
      to inhibit killing may prolong acute and persistent infections. The results from
      this study have also suggested the possibility that the combination of E1A with
      TRAIL could be used in the treatment of human malignancy, or in the selection of
      the optimal adenovirus mutant as effective delivering vector for cancer therapy.

PMID- 15555549
TI  - Targeted disruption of mouse ortholog of the human MYH9 responsible for
      macrothrombocytopenia with different organ involvement: hematological,
      nephrological, and otological studies of heterozygous KO mice.
AB  - Among three different isoforms of non-muscle myosin heavy chains (NMMHCs), only
      NMMHCA is associated with inherited human disease, called MYH9 disorders,
      characterized by macrothrombocytopenia and characteristic granulocyte inclusions.
      Here targeted gene disruption was performed to understand fundamental as well as
      pathological role of the gene for NMMHCA, MYH9. Heterozygous intercrosses yielded
      no homozygous animals among 552 births, suggesting that MYH9 expression is
      required for embryonic development. In contrast, MYH9+/- mice were viable and
      fertile without gross anatomical, hematological, and nephrological abnormalities.
      Immunofluorescence analysis also showed the normal cytoplasmic distribution of
      NMMHCA. We further measured the auditory brainstem response and found two of six
      MYH9+/- mice had hearing losses, whereas the remaining four were comparable to
      wild-type mice. Such observation may parallel the diverse expression of Alport's
      manifestations of human individuals with MYH9 disorders and suggest the limited
      requirement of the gene for maintenance and function of specific organs.

PMID- 15555550
TI  - Reconstitution of the basal calcium transport in resealed human red blood cell
      ghosts.
AB  - The (45)Ca(2+) influx into right-side-out resealed ghosts (RG) prepared from
      human red blood cells (RBC) was measured. The (45)Ca(2+) equilibration occurred
      with t(1/2)=2.5 min and the steady-state was reached after 17 min with the level
      of 22+/-2 micromol/L(packed cells) at 37 degrees C. The rate of the influx was
      97+/-17 micromol/L(packed cells)h. The (45)Ca(2+) influx was saturated with
      [Ca(2+)](0) at 4 mmol/L and was optimal at pH 6.5 and 30 degrees C. Divalent
      cations (10(-4)-10(-6)mol/L), nifedipine (10(-5)-10(-4)mol/L), DIDS (up to 10(
      4)mol/L), and quinidine (10(-4)-10(-3)mol/L), inhibited the (45)Ca(2+) influx
      while uncoupler (10(-6)-10(-5)mol/L) stimulated it. In contrast to intact RBC,
      vanadate inhibited the (45)Ca(2+) influx when added to the external medium,
      however, the stimulation was observed when vanadate was present in media during
      both lysis and resealing. PMA had no effect under conditions found to stimulate
      the Ca(2+) influx in intact RBC. The results show that the Ca(2+) influx into RG
      is a carrier-mediated process but without control by protein kinase C and that
      the influx and efflux of Ca(2+) are coupled via the H(+) homeostasis similarly as
      in intact RBC but with modified mechanism.

PMID- 15555551
TI  - The human pituitary nitroproteome: detection of nitrotyrosyl-proteins with two
      dimensional Western blotting, and amino acid sequence determination with mass
      spectrometry.
AB  - Nitric oxide is an important mediator that participates in reduction-oxidation
      (redox) mechanisms and in cellular signal transduction pathways. Two types of
      post-translational modifications are induced by nitric oxide: S-nitrosylation of
      cysteine residues and nitration of tyrosine residues. Two-dimensional gel
      electrophoresis-based Western blotting was used to detect, and liquid
      chromatography (LC)-tandem mass spectrometry (MS/MS) to determine the amino acid
      sequence of, several different nitrated proteins in the human pituitary. Proteins
      from several 2D gel spots, which corresponded to the strongly positive anti
      nitrotyrosine Western blot spots, were subjected to in-gel trypsin-digestion and
      LC-MS/MS analysis. MS/MS, SEQUEST analysis, and de novo sequencing were used to
      determine the nitration site of each nitrated peptide. A total of four different
      nitrated peptides were characterized and were matched to four different proteins:
      synaptosomal-associated protein, actin, immunoglobulin alpha Fc receptor, and
      cGMP-dependent protein kinase 2. Those nitrotyrosyl-proteins participate in
      neurotransmission, cellular immunity, and cellular structure and mobility.

PMID- 15555552
TI  - The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human
      vascular smooth muscle cells and is induced by interferon gamma.
AB  - Atherosclerosis is an inflammatory disease that is characterised by the
      involvement of chemokines that are important for the recruitment of leukocytes
      and scavenger receptors that mediate foam cell formation. Several cytokines are
      involved in the regulation of chemokines and scavenger receptors in
      atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in
      macrophages in human atherosclerotic lesions. Using double-labelled
      immunohistochemistry, we identified that smooth muscle cells in human lesions
      express CXCL16. We then analysed the effects of IFN-gamma, TNF-alpha, IL-12, IL
      15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells.
      IFN-gamma was the most potent CXCL16 inducer and increased mRNA, soluble form,
      membrane form, and total cellular levels of CXCL16. The IFN-gamma induction of
      CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken
      together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which
      may play a role in the attraction of T cells to atherosclerotic lesions and
      contribute to the cellular internalisation of modified LDL.

PMID- 15555553
TI  - Role of a new member of IGFBP superfamily, IGFBP-rP10, in proliferation and
      differentiation of osteoblastic cells.
AB  - Bone regeneration is critically regulated by various molecules. To identify the
      new genes involved in bone regeneration, we performed microarray-based gene
      expression analysis using a mouse bone regeneration model. We identified a new
      member of the IGFBP superfamily, designated IGFBP-rP10, whose expression is up
      regulated at the early phase of bone regeneration. IGFBP-rP10 consists of an
      IGFBP homologous domain followed by a Kazal-type protein inhibitor domain and an
      immunoglobulin G-like domain. A real-time-based RT-PCR analysis demonstrated that
      various tissues including bone expressed IGFBP-rP10 mRNA in various degrees, and
      confirmed an up-regulation at the early phase of bone regeneration. In situ
      hybridization revealed that osteoblastic cells expressed IGFPB-rP10 mRNA during
      bone regeneration. Bone morphogenetic protein-2 increased the expression level of
      IGFBP-rP10 mRNA in various cells including C3H10T1/2, MC3T3-E1, C2C12, and
      primary murine osteoblastic cells. The addition of recombinant mouse IGFBP-rP10
      promoted the proliferation of these cells but failed to stimulate alkaline
      phosphatase activity. These results suggest that IGFBP-rP10 is involved in the
      proliferation of osteoblasts during bone formation and bone regeneration.

PMID- 15555554
TI  - 2D7 diabody bound to the alpha2 domain of HLA class I efficiently induces caspase
      independent cell death against malignant and activated lymphoid cells.
AB  - A mouse monoclonal antibody (2D7 mAb), which specifically bound to the alpha2
      domain of HLA class I, rapidly induces cell aggregation accompanied by weak
      cytotoxicity against ARH-77 cells, suggesting that 2D7 mAb had a potential for
      agonist antibody. In order to enhance this cytotoxicity, 2D7 mAb was engineered
      to be a small bivalent antibody fragment, 2D7 diabody. The resultant 2D7 diabody
      showed a strong cytotoxicity against ARH-77 cells. As a notable characteristic
      feature, the lethal effect of 2D7 diabody was quite rapid, mediated by a caspase
      independent death pathway. Furthermore, 2D7 diabody also showed cytotoxicity
      against several leukemia and lymphoma cell lines, and mitogen-activated
      peripheral blood mononuclear cells (PBMC), but not for normal resting PBMC and
      adherent cell lines such as HUVEC. These results suggest that 2D7 diabody could
      be expected as a novel therapeutic antibody for hematological malignancies as
      well as inflammatory diseases.

PMID- 15555555
TI  - Prediction of quaternary assembly of SARS coronavirus peplomer.
AB  - The tertiary structures of the S1 and S2 domains of the spike protein of the
      coronavirus which is responsible of the severe acute respiratory syndrome (SARS)
      have been recently predicted. Here a molecular assembly of SARS coronavirus
      peplomer which accounts for the available functional data is suggested. The
      interaction between S1 and S2 appears to be stabilised by a large hydrophobic
      network of aromatic side chains present in both domains. This feature results to
      be common to all coronaviruses, suggesting potential targeting for drugs
      preventing coronavirus-related infections.

PMID- 15555556
TI  - Chrysin-induced apoptosis is mediated through caspase activation and Akt
      inactivation in U937 leukemia cells.
AB  - Chrysin is a natural, biologically active compound extracted from many plants,
      honey, and propolis. It possesses potent anti-inflammation, anti-cancer, and anti
      oxidation properties. The mechanism by which chrysin initiates apoptosis remains
      poorly understood. In the present report, we investigated the effect of chrysin
      on the apoptotic pathway in U937 human promonocytic cells. We show that chrysin
      induces apoptosis in association with the activation of caspase 3 and that Akt
      signal pathway plays a crucial role in chrysin-induced apoptosis in U937 cells.
      Furthermore, we have shown that inhibition of Akt phosphorylation in U937 cells
      by the specific PI3K inhibitor, LY294002 significantly, enhanced apoptosis.
      Overexpression of a constitutively active Akt (myr-Akt) in U937 cells inhibited
      the induction of apoptosis, activation of caspase 3, and PLC-gamma1 cleavage by
      chrysin. Together, these findings suggest that the Akt pathway plays a major role
      in regulating the apoptotic response of human leukemia cells to chrysin and raise
      the possibility that combined interruption of chrysin and PI3K/Akt-related
      pathways may represent a novel therapeutic strategy in hematological
      malignancies.

PMID- 15555557
TI  - Selective brain responses to acute and chronic low-dose X-ray irradiation in
      males and females.
AB  - Radiation exposure is known to have profound effects on the brain, leading to
      precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8
      (2002) 955]. Although a plethora of data exist on the effects of high radiation
      doses, the effects of low-dose irradiation, such as ones received during
      repetitive diagnostic and therapeutic exposures, are still under-investigated
      [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889;
      Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological
      effects of ionizing radiation have been performed using a single acute dose,
      while clinically and environmentally relevant exposures occur predominantly under
      chronic/repetitive conditions. Here, we have used a mouse model to compare the
      effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5Gy)
      to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44
      MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have
      been previously shown to be crucial for neuronal survival upon irradiation. We
      report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive
      low-dose exposure in the hippocampus and frontal cortex of mice. These studies
      were paralleled by the analysis of radiation effects on neurogenesis and cellular
      proliferation. Repetitive exposure had a much more pronounced effect on cellular
      signaling and neurogenesis than acute exposure. These results suggest that
      studies of single acute exposures might be limited in terms of their predictive
      value. We also present the first evidence of sex differences in radiation-induced
      signaling in the hippocampus and frontal cortex. We show the role of estrogens in
      brain radiation responses and discuss the implications of the observed changes.

PMID- 15555558
TI  - Rapid profiling of the infection of Bacillus anthracis on human macrophages using
      SELDI-TOF mass spectroscopy.
AB  - Anthrax is an infectious disease caused by toxigenic strains of the Gram-positive
      bacterium Bacillus anthracis, which is mainly present in the environment in the
      form of highly resistant spores. In order to elucidate a surface enhanced laser
      desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy analysis to
      profile different expressed proteins when B. anthracis spores are infected in
      human macrophages, we analyzed human macrophage cytosolic fractions for the
      infection of B. anthracis spores. Eleven different protein peaks were obtained.
      The 8217.8 kDa was increased specifically in inactivated-Sterne spores at 90 min.
      At 120 min, the peak of 8552.1 kDa in the inactivate-Sterne spores increased more
      than fourfold compared to live-Sterne spores. The protein peak at 8552.1kDa
      suggests that inactivated-Sterne spores could cause the phagolysosome formation
      of macrophages. And the protein peaks that increased in live-Sterne spores
      suggest that it could escape from the phagolysosome of the macrophage. These
      SELDI-TOF profiles assume an important role in human macrophage for the survival
      and escape of the infected B. anthracis spores.

PMID- 15555559
TI  - C6 glioma cells retrovirally engineered to express IL-18 and Fas exert FasL
      dependent cytotoxicity against glioma formation.
AB  - The decreased antitumor immune response significantly contributes to the
      progression of glioma. To evaluate whether the antitumor immunity is restored by
      stable co-expression of IL-18 and Fas receptor, we retrovirally introduced these
      two genes into rat C6 glioma cells. We found that IL-18-transduced glioma cells
      secreted IL-18 and induced PBMC IFN-gamma production in vitro. We also found that
      Fas-transduced glioma cells were susceptible to Fas-mediated apoptosis. In vivo,
      we found that IL-18 expression and Fas expression synergistically inhibited C6
      cell tumorigenesis with the glioma cells being subcutaneously injected in rat
      flank. Furthermore, we found that co-expression of IL-18 and Fas also produced a
      marked survival advantage with the rats being intracerebrally implanted with the
      glioma cells. Finally, we demonstrated that FasL-dependent PBMC cytotoxicity
      participated in the anti-glioma immunity induced by IL-18 and Fas expression.
      Taken together, these findings demonstrate that increasing IL-18 production in
      tumor microenvironment and prompting functional Fas receptor expression of tumor
      cells could enhance FasL-dependent cytotoxic antitumor immunity.

PMID- 15555560
TI  - Regulation of procaspase-2 by glucocorticoid modulatory element-binding protein 1
      through the interaction with caspase recruitment domain.
AB  - Caspases are the primary executioners of apoptosis. Although procaspases believe
      to exist as inactive forms in cells, the detailed regulatory system remains
      unclear. Here we show that glucocorticoid modulatory element-binding protein 1
      (GMEB1) is capable of binding to the prodomain of caspase-2. We found that this
      molecule inhibits the autoproteolytic activation of procaspase-2 by
      oligomerization on a chemical compound-dependent system. These findings indicated
      that GMEB1 might be an endogenous inhibitory protein that selectively interacts
      with prodomain of caspase-2 to disrupt the autoactivation.

PMID- 15555561
TI  - Correspondence analysis of amino acid usage within the family Bacillaceae.
AB  - When the amino acid usage of all completely sequenced prokaryotes is studied by
      multivariate analysis (MVA), it is known that the genomic molar content of
      guanine plus cytosine (GC) and optimal growth temperature (Topt) have a dominant
      effect. Furthermore, these two factors are associated to the first two axes of
      different MVA, and thus, nearly independent among them. However, it was recently
      shown that for several Families of prokaryotes there are significant and positive
      correlations between GC and Topt. This trend is particularly clear within
      Bacillaceae, where there are species displaying a broad range of variations for
      these two factors. In this paper we report that (a) Topt and genomic GC are the
      main factors shaping amino acid usage but are not independent between them, (b)
      the usage of cysteine is the second source of variability, and finally (c) the
      global hydrophobicity of the encoded proteins of each species is the third main
      factor.

PMID- 15555562
TI  - Rapid in vivo transport of proteins from digested allergen across pre-sensitized
      gut.
AB  - Although the route of sensitization to food allergens is still the subject of
      debate, it is generally accepted the gut immune system plays a pivotal role.
      However, hitherto the transport of allergens across the normal, pre-sensitized
      gut epithelium remained largely unknown. Our aim was to identify the route
      through which protein bodies and soluble proteins from digested peanuts
      penetrated the pre-sensitized gut epithelium in vivo and the specific cell types
      involved in the transport. Digestion of peanuts released a large number of
      protein bodies that are exclusively transported across the epithelium by
      specialized antigen-sampling M cells and delivered to the lymphoid tissue of
      Peyer's patch. Intracellular transport of soluble protein also occurred almost
      exclusively via M cells and it was negligible across absorptive enterocytes. We
      hypothesize that these conditions which are known to favour strongly the
      induction of immune responses rather than oral tolerance may play a significant
      role in the genesis of allergic reactions.

PMID- 15555563
TI  - Glucocorticoids decrease the bioavailability of TGF-beta which leads to a reduced
      TGF-beta signaling in hepatic stellate cells.
AB  - Glucocorticoids bound to their receptors transmit information, which regulates
      numerous physiological and pathophysiological responses, amongst others glucose
      metabolism, wound healing, inflammation, and stress, either directly as
      transcription factors by binding DNA elements of target genes or indirectly by
      protein-protein interactions with other transcription factors. TGF-beta, a key
      factor in activation of hepatic stellate cells (HSC), induces production of
      extracellular matrix, this being a prerequisite for the development of liver
      fibrosis. Glucocorticoids and their receptors may provide a crosstalk with the
      TGF-beta-Smad signaling pathway by antagonizing TGF-beta effects. We studied the
      influence of glucocorticoids on the TGF-beta isoform and Smad mRNA expression,
      TGF-beta secretion, and signaling in activated HSC using gene-specific real-time
      PCR, ELISA, and transfection techniques. Dexamethasone treatment reduces TGF-beta
      mRNA transcription in a time-dependent manner. Activated HSC produce TGF-beta and
      secrete it into the cell culture medium. After dexamethasone treatment, TGF-beta
      secretion into the medium is reduced dose-dependently but restorable by
      mifepristone. Further, we found that reduced secretion of endogenous TGF-beta is
      accompanied by a reduced TGF-beta signal. Additionally, reporter gene analysis
      after adenoviral infection with a recombinant virus encoding a Smad-binding
      element showed that TGF-beta-Smad signaling is significantly down-regulated by
      dexamethasone in primary HSC and CFSC, a HSC related cell line. Our data suggest
      that glucocorticoids inhibit TGF-beta expression, prevent TGF-beta from efficient
      secretion, and finally lead to reduced TGF-beta signaling in primary HSC.

PMID- 15555564
TI  - Structural studies of metal-free metallothionein.
AB  - We report the first molecular dynamics calculations on the structure of metal
      free betaalpha recombinant human metallothionein, with comparison to the two
      isolated fragments, alpha-rhMT and beta-rhMT, starting from a linear synthesized
      strand as well as a demetallated conformation. Following a 5000 ps MM3/MD
      calculation, the cysteine side chains were found to populate the outside surface
      of the metal-free protein, regardless of the initial conformation. The
      polypeptide backbone adopted a random coil conformation when starting from the
      linear strand, however, it retained a significant amount of secondary structure
      when starting from the demetallated conformation. We propose that the inverted
      cysteinyl sulfur orientation facilitates the binding of the metal ions to form
      the proteolytically stable, metallated protein.

PMID- 15555565
TI  - The FHA domain of aprataxin interacts with the C-terminal region of XRCC1.
AB  - Aprataxin (APTX) is the causative gene product for early-onset ataxia with ocular
      motor apraxia and hypoalbuminemia (EAOH/AOA1). In our previous study, we found
      that APTX interacts with X-ray repair cross-complementing group 1 (XRCC1), a
      scaffold protein with an essential role in single-strand DNA break repair (SSBR).
      To further characterize the functions of APTX, we determined the domains of APTX
      and XRCC1 required for the interaction. We demonstrated that the 20 N-terminal
      amino acids of the FHA domain of APTX are important for its interaction with the
      C-terminal region (residues 492-574) of XRCC1. Moreover, we found that poly (ADP
      ribose) polymerase-1 (PARP-1) is also co-immunoprecipitated with APTX. These
      findings suggest that APTX, together with XRCC1 and PARP-1, plays an essential
      role in SSBR.

PMID- 15555566
TI  - Identification of chicken nebulin isoforms of the 31-residue motifs and non
      muscle nebulin.
AB  - Nebulin is a very large (M(r) 600-900kDa) actin-binding protein that is specific
      to skeletal muscle, and which is thought to act as a molecular template that
      regulates the length of sarcomere thin filaments. The 31-residue motif of nebulin
      contains a unique PEhXRVKXNQ consensus sequence. We have previously identified 11
      different human nebulin isoforms of these 31-residue motifs. Here we present the
      identification of seven different isoforms (types II, III, IVa, IVb, V, VI, and
      X) of the 31-residue motifs in 15-day-old chicken embryo breast muscle. Isoform
      types II and III are also expressed in the brain, and type III is also detected
      in the heart, stomach, and liver. Chicken nebulin contains 11 copies of the 31
      residue motif (R1a/b, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11), whereas
      human nebulin contains 13 copies. We confirmed the expression of nebulin in the
      heart, stomach, and brain in 15-day-old chicken embryos by immunofluorescence
      microscopy. The presence of nebulin in brain was further confirmed by in situ
      hybridization. These data suggest that there is even more diversity in nebulin
      isoforms than was previously known; this diversity likely contributes to the
      distinct actin filament architecture of different tissues.

PMID- 15555567
TI  - A novel inhibitor that protects apoptotic DNA fragmentation catalyzed by DNase
      gamma.
AB  - The internucleosomal cleavage of genomic DNA is the biochemical hallmark of
      apoptosis. DNase gamma, a Ca(2+)/Mg(2+)-dependent endonuclease, has been
      suggested to be one of the apoptotic endonucleases. We identified here 4-(4,6
      dichloro-[1,3,5]-triazin-2-ylamino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-benzoic
      acid (DR396) as a novel and potent DNase gamma inhibitor using stable HeLa S3
      transfectants of DNase gamma (HeLa-gamma cells). DR396 inhibited apoptotic DNA
      fragmentation in HeLa-gamma cells induced by staurosporine (STS) and in rat
      splenocytes exposed to gamma-ray irradiation in a dose-dependent manner. This
      compound potently and selectively inhibited DNase gamma activity with an IC(50)
      value of 3.2 microM. DR396 did not delay the apoptotic processes as judged by the
      morphological changes and the cleavage of a death substrate, poly(ADP-ribose)
      polymerase (PARP). Furthermore, the compound did not prevent apoptotic DNA
      fragmentation in Jurkat cells induced by anti-Fas antibody (Ab), which is
      catalyzed by caspase-activated DNase (CAD). These findings clearly indicate that
      DR396 exerts chemical knockdown effect of DNase gamma on cells, suggesting that
      the compound could be an attractive tool for understanding of the physiological
      significance of DNase gamma.

PMID- 15555568
TI  - Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by
      increased expression of nonsteroidal anti-inflammatory drug-activated gene.
AB  - We have investigated whether NAG-1 is induced in oral cavity cancer cells by
      various NSAIDs and if apoptosis induced by NSAIDs can be linked directly with the
      induction of NAG-1. NAG-1 expression was increased by diclofenac, aceclofenac,
      indomethacin, ibuprofen, and sulindac sulfide, in the order of NAG-1 induction,
      but not by acetaminophen, piroxicam or NS-398. Diclofenac was the most effective
      NAG-1 inducer. Incubation with diclofenac inhibited cell proliferation and
      induced apoptosis. The expression of NAG-1 was observed in advance of the
      induction of apoptosis. Conditioned medium from NAG-1-overexpressing Drosophila
      cells inhibited SCC 1483 cells proliferation and induced apoptosis. In summary,
      some NSAIDs induce NAG-1 expression in oral cavity cancer cells and the induced
      NAG-1 protein appears to mediate apoptosis. Therefore, NSAIDs may be considered
      as a possible chemopreventive agent against oral cavity cancer.

PMID- 15555569
TI  - Characterization of a new human isoform of the enigma homolog family specifically
      expressed in skeletal muscle.
AB  - We have identified a fourth member of the enigma homolog (ENH) family within a
      pool of human transcripts specifically expressed in skeletal muscle tissue. This
      new ENH isoform of 215 amino acids is the shorter of the family, it lacks the C
      terminal LIM domains present in ENH1 but contains the N-terminal PDZ domain.
      Northern blot analysis confirmed the muscle specificity of ENH4. Western blot
      studies of muscle tissues using a non-isoform-specific anti-ENH antibody revealed
      that ENH4 is present only in skeletal muscle and that there is a specific
      distribution of ENH members between skeletal and cardiac muscles, which is
      different in human and mouse. ENH4 was found to co-localize in the sarcomeric Z
      band and to interact with alpha-actinin like the other members of the ENH family.
      Two additional new ENH4 partners of about 34 and 54kDa were also identified.
      These results bring new lights on the ENH protein family members.

PMID- 15555570
TI  - Identification and functional analysis of consensus androgen response elements in
      human prostate cancer cells.
AB  - Androgen receptor (AR) recognizes and binds to 15-bp palindromic androgen
      response element (ARE) sequences with high affinity in vitro, which consist of
      two hexameric half-sites arranged as inverted repeats with a 3-bp spacer.
      Although a few near-consensus ARE sequences have been actually identified in the
      transcriptional regulatory regions of androgen-responsive genes, it has been
      unclear whether the exact consensus sequences function as bona fide AREs in vivo.
      A genome-wide in silico screening of palindromic AREs identified 563 exact
      consensus sequences in the human genome. The distribution of perfect palindromic
      AREs among the chromosomes is basically consistent with the length of
      chromosomes. Using human prostate cancer cell line LNCaP treated with a synthetic
      androgen R1881 as a model, in vivo AR binding abilities of 21 consensus AREs were
      analyzed by chromatin immunoprecipitation. Of 21 genomic fragments containing
      perfect AREs in chromosome X, 8 fragments recruited more ARs (>4-fold enrichment)
      even compared with the proximal ARE region of prostate-specific antigen. A couple
      of proximal genes or putative transcripts in the vicinity of the perfect AREs
      were found to be androgen-responsive analyzed by quantitative RT-PCR. Our results
      suggest that some of perfect palindromic AREs could function as in vivo AR
      binding sites in the human genome and regulate gene transcription.

PMID- 15555571
TI  - Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma
      with t(7;12).
AB  - "Pericytoma with t(7;12)" is a newly defined soft tissue tumor characterized by
      fusion of the ACTB and GLI genes through the translocation t(7;12)(p22;q13).
      Recently, we reported the structure of the ACTB-GLI and GLI-ACTB fusion
      transcripts in five cases, and herein the corresponding genomic breakpoints were
      investigated. Overall, the findings at the DNA level corresponded well with the
      structure of the expressed transcripts. In three cases, the fusions were due to
      junction of intronic sequences, in two cases breakpoints were found in exonic
      sequences. In four cases the fusions corresponded to the juxtapositioning of
      unaltered DNA sequences, and in one case, a micro-inversion was found at the
      junction. All five fusions were molecularly unbalanced, including the two cases
      with reciprocal GLI-ACTB chimeras. Whereas large repeats or recombinase
      recognition sequences were not detected, sequences of shared oligonucleotides,
      possibly important for recombination, were found in the proximity of the
      respective breakpoints.

PMID- 15555572
TI  - Increased peptidylarginine deiminase type II in hypoxic astrocytes.
AB  - Peptidylarginine deiminase type II (PAD 2) is the primary enzyme responsible for
      conversion of protein bound arginine to citrulline in the central nervous system.
      Evidence suggests that glial fibrillary acidic protein (GFAP), the main
      intermediate filament in astrocytes, is deiminated, but not much is known
      regarding factors that control this enzymatic reaction. The present study
      demonstrated that PAD 2 activity (as determined by Western blot analysis of
      citrullinated GFAP isoforms) was increased in human cultured astrocytes by
      hypoxic conditions. PAD 2 mRNA increased markedly during the first 2h of hypoxia,
      but using a single chain antibody against human PAD 2 produced from the ETH-2
      phage library, it took approximately 8h of hypoxia to see marked increases in PAD
      2 protein. Thus, this is the first report to demonstrate a measurable response in
      the amounts of PAD 2 mRNA, protein and activity in human astrocytes by prolonged
      hypoxic exposure.

PMID- 15555573
TI  - IXL, a new subunit of the mammalian Mediator complex, functions as a
      transcriptional suppressor.
AB  - Transcription factors play an essential role in altering gene expression. Much
      progress about transcription factors has been made toward the understanding of
      normal physiological processes, embryonic development, and human diseases. In the
      present study, we report the identification and characterization of a novel human
      gene, (Drosophila) intersex-like (IXL), from a human embryonic heart cDNA
      library. IXL encodes a putative protein of 221 amino acids. The protein is
      conserved across different species during evolution. Northern blot analysis
      indicates that IXL is expressed in various tissues of human adult and during
      three different developmental stages of embryo. In COS-7 cells, IXL protein is
      localized to nucleus and cytoplasm. IXL is a transcription suppressor when fused
      to Gal-4 DNA-binding domain and cotransfected with VP-16. Overexpression of IXL
      in COS-7 cells inhibits the transcriptional activities of SRE and AP-1,
      suggesting that the IXL protein may act as a transcriptional suppressor in
      mitogen-activated protein kinase signaling pathway to mediate cellular functions.

PMID- 15555574
TI  - Molecular classification of scrapie strains in mice using gene expression
      profiling.
AB  - Transmissible spongiform encephalopathy strains demonstrate specific prion
      characteristics, each with specific incubation times, and strain-specific
      patterns of deposition of the misfolded isoform of prion, PrPSc, in the brains of
      infected individuals. Different biochemical properties, including glycosylation
      profiles and the degree of proteinase resistance, have been shown to be strain
      specific. However, no relationship between these properties and the phenotypic
      differences in the subsequent diseases has as yet been determined. Here we
      explore the utility of gene expression profiles to identify differences in the
      host response to different strains of prion agent. We identify 114 genes that
      exhibit significantly different levels of expression in mice infected with three
      strains of scrapie. These genes represent a pool of genes involved in a strain
      specific response to prion disease. We have identified the most discriminatory
      genes from this list utilizing a wrapper-based feature selection algorithm with
      external cross-validation.

PMID- 15555575
TI  - Application of amplified RNA and evaluation of cRNA targets for spotted
      oligonucleotide microarray.
AB  - Among different RNA amplification methods, T7 RNA polymerase-based in vitro
      transcription (IVT) that generates antisense RNA is most common in DNA microarray
      protocol. However, despite the fact that cRNA targets labeled during IVT are
      feasible for spotted-oligonucleotide microarray (spotted-oligoarray)
      hybridization due to complementary sequence of single-stranded oligonucleotide
      probe, no systemic assessment for the use of amplified cRNA targets has been
      reported for spotted-oligoarrays. In this investigation, we have compared the
      hybridization performance of amplified cRNA targets with that of cDNA targets
      from total RNA(T-RNA) using spotted-oligoarrays containing 18,864 genetic
      elements. Under the optimized hybridization conditions, we found that 86% of
      oligonucleotide probes were reproducibly detected by both cDNA and cRNA target
      protocols. In addition, cRNA targets generated by two-rounds of amplification of
      10 ng T-RNA were concordant with first-round cRNA targets generated from 100 ng T
      RNA by 0.858 of correlation coefficient. Taken together, we demonstrated that
      cRNA targets from very scant RNA amount could successfully be applied on spotted
      oligoarrays, and hopefully this will facilitate the application of much smaller
      amount of source material based on the high-fidelity and improved target
      preparation of microarrays.

PMID- 15555576
TI  - Effects of G-CSF on cardiac remodeling after acute myocardial infarction in
      swine.
AB  - We examined whether granulocyte colony-stimulating factor (G-CSF) prevents
      cardiac dysfunction and remodeling after myocardial infarction (MI) in large
      animals. MI was produced by ligation of left anterior descending coronary artery
      in swine. G-CSF (10 microg/kg/day, once a day) was injected subcutaneously from
      24h after ligation for 7 days. Echocardiographic examination revealed that the G
      CSF treatment induced improvement of cardiac function and attenuation of cardiac
      remodeling at 4 weeks after MI. In the ischemic region, the number of apoptotic
      endothelial cells was smaller and the number of vessels was larger in the G-CSF
      treatment group than in control group. Moreover, vascular endothelial growth
      factor was more abundantly expressed and Akt was more strongly activated in the
      ischemic region of the G-CSF treatment group than of control group. These
      findings suggest that G-CSF prevents cardiac dysfunction and remodeling after MI
      in large animals.

PMID- 15555577
TI  - A downstream enhancer is essential for Xenopus FoxD5 transcription.
AB  - We have isolated and sequenced the pseudo-allelic versions of FoxD5 genes in
      Xenopus laevis, xlFoxD5a and xlFoxD5b, and the xtFoxD5 gene of Xenopus
      tropicalis. These genes show a highly conserved structure, they are composed of
      only one exon, and they exhibit a high degree of sequence conservation within
      their flanking sequences. The X. tropicalis gene is expressed like its X. laevis
      orthologues in progenitor cells of the neural floor plate. Serial deletions of
      the 5'- and 3'-flanking region in combination with reporter gene assays
      demonstrate that a distal and a proximal upstream element as well as a downstream
      located enhancer do mainly contribute to transcriptional activity. The downstream
      enhancer cooperates with the proximal upstream element and also contributes to
      the spatial expression. Transgenic animals express enhanced green fluorescent
      protein in a spatial pattern like xlFoxD5b, when the 5'- and 3'-flanking regions
      of the xlFoxD5b gene are used to direct transgene expression.

PMID- 15555578
TI  - Involvement of caspase-9 in execution of the maternal program of apoptosis in
      Xenopus late blastulae overexpressed with S-adenosylmethionine decarboxylase.
AB  - We previously demonstrated that overexpression of S-adenosylmethionine
      decarboxylase (SAMDC) in Xenopus early embryos induces execution of maternal
      program of apoptosis shortly after midblastula transition, which likely serves as
      a fail-safe mechanism of early development to eliminate physiologically damaged
      cells before they entering the gastrula stage. To determine how caspases are
      involved in this process, we microinjected peptide inhibitors and "dominant
      negative forms" of caspase-9 and -1 into Xenopus fertilized eggs, and found that
      inhibitors of caspase-9, but not caspase-1, completely suppress SAMDC-induced
      apoptosis. The lysate of SAMDC-overexpressing late blastulae contained activity
      to cleave in vitro-synthesized [(35)S]procaspase-9, but not [(35)S]procaspase-1,
      and mRNA for caspase-9, but not caspase-1, occurred abundantly in the
      unfertilized egg as maternal mRNA. We also found that overexpression of caspase-9
      and -1 equally executes the apoptosis, but the apoptosis executed by these mRNAs
      was only partially rescued by Bcl-2 and rescued embryos did not develop beyond
      neurula stage. These results indicate that activation of caspase-9 is a key step
      for execution of the maternally preset program of apoptosis in Xenopus early
      embryos.

PMID- 15555579
TI  - Effect of zeta-globin substitution on the O2-transport properties of Hb S in
      vitro and in vivo.
AB  - Hemoglobin zeta(2)beta(2)(S) is generated by substituting embryonic zeta-globin
      subunits for the normal alpha-globin components of Hb S (alpha(2)beta(2)(S)).
      This novel hemoglobin has recently been shown to inhibit polymerization of Hb S
      in vitro and to normalize the pathological phenotype of mouse models of sickle
      cell disease in vivo. Despite its promise as a therapeutic tool in human disease,
      however, the basic O(2)-transport properties of Hb zeta(2)beta(2)(S) have not yet
      been described. Using human hemoglobins purified from complex transgenic-knockout
      mice, we show that Hb zeta(2)beta(2)(S) exhibits an O(2) affinity as well as a
      Hill coefficient, Bohr response, and allosteric properties in vitro that are
      suboptimally suited for physiological O(2) transport in vivo. These data are
      substantiated by in situ analyses demonstrating an increase in the O(2) affinity
      of intact erythrocytes from mice that express Hb zeta(2)beta(2)(S). Surprisingly,
      though, co-expression of Hb zeta(2)beta(2)(S) leads to a substantial improvement
      in the tissue oxygenation of mice that model sickle cell disease. These analyses
      suggest that, in the context of sickle cell disease, the beneficial antisickling
      effects of Hb zeta(2)beta(2)(S) outweigh its O(2)-transport liabilities. The
      potential structural bases for the antisickling properties of Hb
      zeta(2)beta(2)(S) are discussed in the context of these new observations.

PMID- 15555580
TI  - ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates
      transcriptional activation in MAPK signaling pathways.
AB  - Cardiac differentiation involves a cascade of coordinated gene expression that
      regulates cell proliferation and matrix protein formation in a defined temporal
      spatial manner. The C(2)H(2) zinc finger-containing transcription factors have
      been implicated as critical regulators of multiple cardiac-expressed genes and
      are important for human heart development and diseases. Here we have identified
      and characterized a novel zinc-finger gene named ZNF322 using degenerated primers
      from a human embryo heart cDNA library. The gene contains four exons and spans
      23.2kb in chromosome 6p22.1 region, and transcribes a 2.7kb mRNA that encodes a
      protein with 402 amino acid residues. The predicted protein contains 9 tandem
      C(2)H(2)-type zinc-finger motifs. Northern blot analysis shows that ZNF322 is
      expressed in every human tissue examined at adult stage and during embryonic
      developmental stages from 80 days to 24 weeks. When overexpressed in COS-7 cells,
      ZNF322-EGFP fusion protein is detected in the nucleus and cytoplasm. Reporter
      gene assays show that ZNF322 is a transcriptional activator. Furthermore,
      overexpression of ZNF322 in COS-7 cells activates the transcriptional activity of
      SRE and AP-1. Together, these results suggest that ZNF322 is a member of the zinc
      finger transcription factor family and may act as a positive regulator in gene
      transcription mediated by the MAPK signaling pathways.

PMID- 15555581
TI  - Multifaceted role of galectin-3 on human glioblastoma cell motility.
AB  - Astrocytic tumors' aggressiveness results from an imbalance between cell
      proliferation and cell death favoring growth, but also from the propensity of
      tumor cells to detach from the primary tumor site, migrate, and invade the
      surrounding parenchyma. Astrocytic tumor progression is known to be associated
      with an increased expression of galectin-3. We investigated in cell culture how
      galectin-3 expression affects astrocytoma cell motility. Galectin-3 deficient
      cells were obtained by stable transfection of the U373 glioblastoma cell line
      with a specific expression antisense plasmid. Cultured galectin-3 deficient
      glioblastoma cells showed increased motility potential on laminin and
      modifications in the cytoskeleton reorganization. In addition, c-DNA microarrays
      and quantitative immunofluorescence analysis showed that galectin-3 deficient
      U373 cells have an increased expression of integrins-alpha6 and -beta1, proteins
      known to be implicated in the regulation of cell adhesion.

PMID- 15555582
TI  - Cellular aging of mitochondrial DNA-depleted cells.
AB  - We have reported that mitochondrial DNA-depleted rho(0) cells are resistant to
      cell death. Because aged cells have frequent mitochondrial DNA mutations, the
      resistance of rho(0) cells against cell death might be related to the apoptosis
      resistance of aged cells and frequent development of cancers in aged individuals.
      We studied if rho(0) cells have features simulating aged cells. SK-Hep1 hepatoma
      rho(0) cells showed typical morphology associated with aging such as increased
      size and elongated appearance. They had increased senescence-associated beta-Gal
      activity, lipofuscin pigment, and plasminogen activator inhibitor-1 expression.
      Consistent with their decreased proliferation, the expression of mitotic cyclins
      was decreased and that of cdk inhibitors was increased. Rb hypophosphorylation
      and decreased telomerase activity were also noted. Features simulating aged cells
      were also observed in MDA-MB-435 rho(0) cells. These results support the
      mitochondrial theory of aging, and suggest that rho(0) cells could serve as an in
      vitro model for aged cells.

PMID- 15555583
TI  - Synthetic human prion protein octapeptide repeat binds to the proteinase K active
      site.
AB  - Proteinase K is widely used in tests for the presence of infectious prion protein
      causing fatal spongiform encephalopathies. To investigate possible interactions
      between the enzyme and the functionally important N-terminal prion domain, we
      crystallized mercury-inhibited proteinase K in the presence of the synthetic
      peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a
      single octapeptide repeat (OPR) from the physiologically important OPR region.
      Here, we present the first direct evidence for the complex formation between a
      proteolytic enzyme and a segment of human prion molecule. The X-ray structures of
      the complexes at 1.4 and 1.8A resolution, respectively, revealed that in both
      cases the segment GGG is strongly bound as a real substrate at the substrate
      recognition site of the proteinase forming an antiparallel beta-strand between
      the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is
      stabilized through an extended H-bonding network.

PMID- 15555584
TI  - Regulation of tyrosinase by tetrahydropteridines and H2O2.
AB  - Recently two alternative mechanisms have been put forward for the inhibition of
      tyrosinase by 6R-l-erythro 5,6,7,8-tetrahydrobiopterin (6BH(4)). Initially
      allosteric uncompetitive inhibition was demonstrated due to 1:1 binding of 10(
      6)M 6BH(4) to a specific domain 28 amino acids away from the Cu(A) active site of
      the enzyme. Alternatively it was then shown that 10(-3)M 6BH(4) inhibit the
      reaction by the reduction of the product dopaquinone back to l-dopa. In the study
      presented herein we have used two structural analogues of 6BH(4) (i.e., 6,7-(R,S)
      dimethyl tetrahydrobiopterin and 6-(R,S)-tetrahydromonapterin) confirming
      classical uncompetitive inhibition due to specific binding of the pyrimidine ring
      of the pterin moiety to the regulatory domain on tyrosinase. Under these
      conditions there was no reduction of l-dopaquinone back to l-dopa by both
      cofactor analogues. Inhibition of tyrosinase by 6BH(4) occurs in the
      concentration range of 10(-6)M after preactivation with l-tyrosine and this
      mechanism uncouples the enzyme reaction producing H(2)O(2) from O(2). Moreover, a
      direct oxidation of 6BH(4) to 7,8-dihydrobiopterin by tyrosinase in the absence
      of the substrate l-tyrosine was demonstrated. The enzyme was activated by low
      concentrations of H(2)O(2) (<0.3 x 10(-3)M), but deactivated at concentrations in
      the range 0.5-5.0 x 10(-3)M. In summary, our results confirm a major role for
      6BH(4) in the regulation of human pigmentation.

PMID- 15555585
TI  - The unusual redox properties of flavocytochrome P450 BM3 flavodoxin domain.
AB  - Flavocytochrome P450 BM3 FMN domain is unique among the family of flavodoxins and
      homologues, in not forming a stable neutral blue FMN semiquinone radical.
      Anaerobic, one-electron reduction of the isolated domain over the pH 7-9.5 range
      showed that it forms an anionic red semiquinone that disproportionates slowly
      (0.014s(-1) at pH 7). The rate of disproportionation decreased at higher pH,
      indicating that protonation of the anionic semiquinone is an important feature of
      the mechanism. The reduction potential for the oxidised-semiquinone couple was
      determined to be -240mV and was largely independent of pH. The semiquinone
      appears, therefore, to be kinetically trapped by a slow protonation event,
      enabling it to act as a low-potential electron donor to the P450 heme.

PMID- 15555586
TI  - Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast.
AB  - The Mcs6 CDK together with its cognate cyclin Mcs2 represents the CDK-activating
      kinase (CAK) of fission yeast Cdc2. We have attempted to determine complexes in
      which Mcs6 and Mcs2 mediate this and possible other functions. Here we
      characterize a novel interaction between Mcs2 and Skp1, a component of the SCF
      (Skp1-Cullin-F box protein) ubiquitin ligase. Furthermore, we identify a novel
      protein termed Pmh1 through its association with Skp1. Pmh1 associates with the
      Mcs6-Mcs2 complex, enhancing its kinase activity, and represents the apparent
      homolog of metazoan Mat1. Association of Mcs2 or Pmh1 with Skp1 does not appear
      to be involved in proteolytic degradation, as these complexes do not contain
      Pcu1, and levels of Mcs2 or Pmh1 are not sensitive to inhibition of SCF and the
      26S proteasome. The identified interactions between Skp1 and two regulatory CAK
      subunits may reflect a novel mechanism to modulate activity and specificity of
      the Mcs6 kinase.

PMID- 15555587
TI  - DNA biosensors based on self-assembled carbon nanotubes.
AB  - DNA biosensors based on self-assembled multi-walled carbon nanotubes (MWNTs) were
      described in this paper, in which the probe DNA oligonucleotides were immobilized
      by forming covalent amide bonds between carboxyl groups at the nanotubes and
      amino groups at the ends of the DNA oligonucleotides. Hybridization between the
      probe and target DNA oligonucleotides was confirmed by the changes in the
      voltammetric peak of the indicator of methylene blue. Our results demonstrate
      that the DNA biosensors based on self-assembled MWNTs had a higher hybridization
      efficiency compared to those based on random MWNTs. In addition, the developed
      DNA biosensors also had a high selectivity of hybridization detection.

PMID- 15555588
TI  - Standardization and validation of an alkaline phosphatase-linked immunoassay to
      quantify a plant-derived antibody directed against the hepatitis B virus surface
      antigen.
AB  - Immunopurification is one of the most effective chromatography steps to purify
      the hepatitis B surface antigen, which have successfully been used as an active
      pharmaceutical ingredient of hepatitis B vaccines. Plant-derived antibodies could
      be an appropriated ligand for such purposes because plants are the most cost
      effective production systems and have the additional advantage that plant viruses
      cannot infect humans. In this work, a polyclonal antibody alkaline phosphatase
      linked immunoassay was standardized and validated to quantify a plant-derived
      antibody directed against the HBsAg. The validation of an immunoassay to quantify
      plantibodies is a relatively complex task due to the complexity of the plant
      extract, the low level of expression of this molecule, and the potential
      interferences of endogenous peroxidases contributed by plants. These results
      allow estimating the plant-derived antibody concentration up to 3.81 ng/mL with
      high specificity, precision, and repeatability. The working range of the standard
      curve was between 3.81 and 60 ng/mL, and the intra- and inter-variation
      coefficients were between 10% and 20% in a production process's sample dependent
      way. This enzyme-linked immunosorbent assay is considered valuable to improve the
      design of the purification process and also to obtain a better estimation of the
      antibody expression level and process's recovery.

PMID- 15555589
TI  - GPS: a novel group-based phosphorylation predicting and scoring method.
AB  - Protein phosphorylation is an important reversible post-translational
      modification of proteins, and it orchestrates a variety of cellular processes.
      Experimental identification of phosphorylation site is labor-intensive and often
      limited by the availability and optimization of enzymatic reaction. In silico
      prediction may facilitate the identification of potential phosphorylation sites
      with ease. Here we present a novel computational method named GPS: group-based
      phosphorylation site predicting and scoring platform. If two polypeptides differ
      by only two consecutive amino acids, in particular when the two different amino
      acids are a conserved pair, e.g., isoleucine (I) and valine (V), or serine (S)
      and threonine (T), we view these two polypeptides bearing similar 3D structures
      and biochemical properties. Based on this rationale, we formulated GPS that
      carries greater computational power with superior performance compared to two
      existing phosphorylation sites prediction systems, ScanSite 2.0 and PredPhospho.
      With database in public domain, GPS can predict substrate phosphorylation sites
      from 52 different protein kinase (PK) families while ScanSite 2.0 and PredPhospho
      offer at most 30 PK families. Using PKA as a model enzyme, we first compared
      prediction profiles from the GPS method with those from ScanSite 2.0 and
      PredPhospho. In addition, we chose an essential mitotic kinase Aurora-B as a
      model enzyme since ScanSite 2.0 and PredPhospho offer no prediction. However, GPS
      offers satisfactory sensitivity (94.44%) and specificity (97.14%). Finally, the
      accuracy of phosphorylation on MCAK predicted by GPS was validated by
      experimentation, in which six out of seven predicted potential phosphorylation
      sites on MCAK (Q91636) were experimentally verified. Taken together, we have
      generated a novel method to predict phosphorylation sites, which offers greater
      precision and computing power over ScanSite 2.0 and PredPhospho.

PMID- 15555590
TI  - Plasma albumin cysteinylation is regulated by cystathionine beta-synthase.
AB  - High homocysteine (Hcy) levels are a well-known independent risk factor for
      endothelial damage in atherosclerosis. We examined whether a rat intestinal model
      of ischemia-reperfusion was associated with high Hcy and with the modification of
      plasma albumin into cysteinylated species (CysAlb). The three treatment groups
      were as follows: midline abdominal incision (group A, n=10), followed by ligation
      of the superior mesenteric artery for a period of 2h (group B, n=3), and followed
      by reperfusion for 1h (group C, n=10). Hcy levels were 2.5-fold higher in group C
      than group A (p<0.05). 100% and 73.44+/-0.04% of Alb were modified into Cys
      species in groups C and B, respectively, compared to 51.2% in group A. A
      cystathionine beta-synthase (CBS) deficient mouse model, known to have high
      plasma Hcy levels, was also used to determine the extent of CysAlb. Hcy levels,
      %CysAlb, and %HcyAlb were 180.1+/-45.7 microM, 0%, and 23.4+/-4.4% in CBS
      deficient mice, while in control mice, those values were 5.7+/-1.8 microM, 24.2+/
      4.1%, and 0%, respectively (p<0.05). High CysAlb and Hcy levels were observed in
      a rat model of bowel ischemia/reperfusion while high HcyAlb and Hcy levels with
      no CysAlb were observed in the CBS deficient mice. CysAlb may serve as a
      biomarker for the severity of gut ischemia, and high Hcy may explain endothelial
      damage associated with this model. Additionally, active CBS is essential for the
      formation of CysAlb.

PMID- 15555591
TI  - The microcin J25 beta-hairpin region is important for antibiotic uptake but not
      for RNA polymerase and respiration inhibition.
AB  - The antibiotic microcin J25 (MccJ25) was cleaved by hydrolysis with thermolysin
      giving a two-chain peptide (MccJ25-Th19) of 10 and 9 amino acid residues. MccJ25
      Th19 with deep modifications in beta-hairpin region had no effect on Escherichia
      coli growth, but still inhibited RNA polymerase in vitro and oxygen consumption
      in Salmonella strains. MccJ25-Th19 showed antibiotic activity on E. coli
      transformed with plasmids containing either fhuA or sbmA genes, which code for
      proteins involved in MccJ25 transport. These results suggest that an intact beta
      hairpin region is crucial for MccJ25 import but not for inhibition of E. coli RNA
      polymerase or oxygen consumption in Salmonella strains.

PMID- 15555592
TI  - HIV LTR-dependent expression of Bax selectively induces apoptosis in Tat-positive
      cells.
AB  - HIV integrates into the host cell genome where it persists for the life of the
      cell. One approach to reducing viral burden is to selectively eliminate cells
      containing integrated provirus early following infection. We have used the HIV
      LTR promoter to selectively express transgenes in human cells positive for the
      HIV transactivator protein Tat. Transient transfection of Jurkat cells, or Jurkat
      cells stably expressing Tat (Jurkat-Tat), with a LTR construct containing
      luciferase reporter gene resulted in a 37-fold increase in gene expression when
      Tat was present. We have demonstrated that when pro-apoptotic Bax was used as the
      transgene, cytotoxicity was seen only in the Jurkat-Tat cells. Annexin-V staining
      indicated that Bax induced cell death by apoptosis. In mixed populations of
      Jurkat and Jurkat-Tat cells, the LTR-Bax construct was selectively cytotoxic to
      the Tat-positive cells. These results suggest that Bax under the control of the
      HIV LTR can be used to destroy cells harbouring HIV without affecting uninfected
      cells.

PMID- 15555593
TI  - Prevention of complement-mediated immune hemolysis by a small molecule compound.
AB  - Complement sensitization of red blood cells (RBCs) can result in transfusion
      reactions and hemolytic anemias. We hypothesized that manipulating the complement
      system using small organic molecules might prevent RBC destruction, thereby
      prolonging RBC survival in patients. Using a simple, rapid, large-scale hemolytic
      assay, we screened a 10,000 compound library, enriched in anti-inflammatory
      compounds at a final concentration of 25 microM, and identified a 549Da compound
      (C(34)H(24)N(6)O(2)) with a symmetrical structure containing two benzimidazole
      rings that, as compared to a known anti-complement molecule FUT-175, was more
      effective in reducing hemolysis by the classical pathway and had comparable anti
      hemolytic activity against the alternative pathway. Furthermore, in a
      xenotransfusion mouse model, treatment of mice with 1.2mg/kg of the compound
      significantly prolonged the survival of transfused RBCs, reducing C3 deposition,
      but not the deposition of control IgG or IgM, for the first hour post
      transfusion. These data suggest that further studies are warranted to determine
      if this compound has usefulness in a transfusion setting.

PMID- 15555594
TI  - Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and
      function through inhibition of MAP kinase activation and actin ring formation.
AB  - Phenolic compounds including tannins and flavonoids have been implicated in
      suppression of osteoclast differentiation/function and prevention of bone
      diseases. However, the effects of hydrolysable tannins on bone metabolism remain
      to be elucidated. In this study, we found that furosin, a hydrolysable tannin,
      markedly decreased the differentiation of both murine bone marrow mononuclear
      cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of
      tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and
      decreased TRAP activity. Furosin appears to target at the early stage of
      osteoclastic differentiation while having no cytotoxic effect on osteoclast
      precursors. Analysis of the inhibitory mechanisms of furosin revealed that it
      inhibited the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced
      activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal
      kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption
      pit formation in osteoclasts, which was accompanied by disruption of the actin
      rings. Taken together, these results demonstrate that naturally occurring furosin
      has an inhibitory activity on both osteoclast differentiation and function
      through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1
      activation as well as actin ring formation.

PMID- 15555595
TI  - Parmodel: a web server for automated comparative modeling of proteins.
AB  - Parmodel is a web server for automated comparative modeling and evaluation of
      protein structures. The aim of this tool is to help inexperienced users to
      perform modeling, assessment, visualization, and optimization of protein models
      as well as crystallographers to evaluate structures solved experimentally. It is
      subdivided in four modules: Parmodel Modeling, Parmodel Assessment, Parmodel
      Visualization, and Parmodel Optimization. The main module is the Parmodel
      Modeling that allows the building of several models for a same protein in a
      reduced time, through the distribution of modeling processes on a Beowulf
      cluster. Parmodel automates and integrates the main softwares used in comparative
      modeling as MODELLER, Whatcheck, Procheck, Raster3D, Molscript, and Gromacs. This
      web server is freely accessible at .

PMID- 15555596
TI  - Lysophospholipase I identified as a ghrelin deacylation enzyme in rat stomach.
AB  - Ghrelin, discovered in rat stomach as an endogenous growth hormone secretagogue,
      is octanoylated at the Ser3 residue. Since this octanoylation is essential for
      the functions of ghrelin, the enzymes that catalyze acylation for ghrelin
      biosynthesis and deacylation (deactivation step) must be considered as important
      regulators. We found that rat stomach homogenate contained ghrelin deacylation
      activity, and we isolated the active fractions by column chromatography. After
      sequencing and expressing candidate proteins, the ghrelin deacylation enzyme in
      the stomach was identified as lysophospholipase I (LysoPLA I). The enzyme
      properties were examined using recombinant rat LysoPLA I expressed in Escherichia
      coli. K(m) and V(max) values were determined as 6.5 microM and 2.3
      micromol/min/mg for ghrelin and 2.2 x 10(2) microM and 0.5 micromol/min/mg for
      lysophosphatidylcholine (LysoPC), respectively. The deacylation of both
      substrates was inhibited by methyl arachidonyl fluorophosphonate (MAFP), which is
      known as an irreversible inhibitor of LysoPLA I. These results reveal that
      LysoPLA I catalyzes the removal of n-octanoic acid from ghrelin to form des-acyl
      ghrelin. Identification of the ghrelin deacylation enzyme in the stomach and a
      deacylation inhibitor will be helpful in investigating ghrelin biosynthesis.

PMID- 15555597
TI  - Drosophila melanogaster CYP6A8, an insect P450 that catalyzes lauric acid (omega
      1)-hydroxylation.
AB  - Only a handful of P450 genes have been functionally characterized from the
      approximately 90 recently identified in the genome of Drosophila melanogaster.
      Cyp6a8 encodes a 506-amino acid protein with 53.6% amino acid identity with
      CYP6A2. CYP6A2 has been shown to catalyze the metabolism of several insecticides
      including aldrin and heptachlor. CYP6A8 is expressed at many developmental stages
      as well as in adult life. CYP6A8 was produced in Saccharomyces cerevisiae and
      enzymatically characterized after catalytic activity was reconstituted with D.
      melanogaster P450 reductase and NADPH. Although several saturated or non
      saturated fatty acids were not metabolized by CYP6A8, lauric acid (C12:0), a
      short-chain unsaturated fatty acid, was oxidized by CYP6A8 to produce 11
      hydroxylauric acid with an apparent V(max) of 25 nmol/min/nmol P450. This is the
      first report showing that a member of the CYP6 family catalyzes the hydroxylation
      of lauric acid. Our data open new prospects for the CYP6 P450 enzymes, which
      could be involved in important physiological functions through fatty acid
      metabolism.

PMID- 15555598
TI  - Clinical evaluation and sequence analysis of the complete mitochondrial genome of
      three Chinese patients with hearing impairment associated with the 12S rRNA
      T1095C mutation.
AB  - Mutations in mitochondrial DNA (mtDNA), particularly those in the 12S rRNA gene,
      have been shown to be associated with sensorineural hearing loss. Here we report
      the clinical and sequence analysis of the entire mitochondrial genome in three
      Chinese subjects with aminoglycoside-induced and non-syndromic hearing
      impairment. Clinical evaluation showed a variable phenotype of hearing impairment
      including the age of onset and audiometric configuration in these subjects.
      Sequence analysis of the complete mitochondrial genomes in three subjects showed
      the distinct sets of mtDNA polymorphism, in addition to the identical
      mitochondrial 12S rRNA T1095C mutation. This mutation was previously identified
      to be associated with hearing impairment in three families from different genetic
      backgrounds. The T1095C mutation was absent in 364 Chinese control. In fact, the
      occurrence of the T1095C mutation in these several genetically unrelated subjects
      affected by hearing impairment strongly indicates that this mutation is involved
      in the pathogenesis of hearing impairment. Among other nucleotide changes, the
      A2238G and T2885C mutations in the 16S rRNA, the I175V mutation in the CO2, the
      F16L mutation in the A6 and the V112M mutation in the ND6 exhibited a high
      evolutionary conservation. These data suggest that the T1095C mutation may be
      associated with aminoglycoside-induced and non-syndromic hearing impairments and
      A2238G and T2885C mutations in the 16S rRNA, the I175V mutation in the CO2, the
      F16L mutation in the A6 and the V112M mutation in the ND6 may contribute to the
      phenotypic expression of the T1095C mutation in these subjects.

PMID- 15555599
TI  - Dynamic interaction of p220(NPAT) and CBP/p300 promotes S-phase entry.
AB  - Cajal bodies contain cyclin E/cdk2 and the substrate p220(NPAT) to regulate the
      transcription of histones, which is essential for cell proliferation, however,
      recent mouse knockout studies indicate that cyclin E and cdk2 are dispensable for
      these events. Because the CBP/p300 histone acetyltransferase are also known to be
      involved in cell proliferation, we examined the molecular and functional
      interactions of p220(NPAT) with the CBP/p300 at the G1/S boundary as cell cycle
      regulators. The subnuclear localization of p220(NPAT) and CBP/p300 proteins
      showed that their foci partially overlapped in a cell cycle dependent manner.
      Overexpression of p220(NPAT) and CBP/p300 cooperatively enhanced G1/S transition
      and DNA synthesis even without cdk2 phosphorylation site. Finally, molecular
      alignment analysis indicated that p220(NPAT) contains several potential substrate
      sites for CBP/p300. Overall, our findings demonstrate that p220(NPAT) and
      CBP/p300 form a transient complex at the G1/S boundary to play cooperative roles
      to promote the S-phase entry.

PMID- 15555600
TI  - A fluorescence-based rapid screening assay for cytotoxic compounds.
AB  - A simple fluorescence-based assay was developed for the rapid screening of
      potential cytotoxic compounds generated by combinatorial chemistry. The assay is
      based on detection of nuclear green fluorescent protein (GFP) staining of a human
      cervical cancer cell line (HeLa) carrying an integrated histone H2B-GFP fusion
      gene. Addition of a cytotoxic compound to the HeLa-GFP cells results in the
      eventual degradation of DNA and loss of the GFP nuclear fluorescence. Using this
      assay, we screened 11 distinct quinone derivatives and found that several of
      these compounds were cytotoxic. These compounds are structurally related to
      plumbagin an apoptosis-inducing naphthoquinone isolated from Black Walnut. In
      order to determine the mechanism by which cell death was induced, we performed
      additional experiments with the most cytotoxic quinones. These compounds were
      found to induce morphological changes (blebbing and nuclear condensation)
      consistent with induction of apoptosis. Additional tests revealed that the
      cytotoxic compounds induce both necrotic and apoptotic modes of death.

PMID- 15555601
TI  - Interaction of phospholipid dispersions with water-soluble porphyrins as
      monitored by their Raman temperature profiles.
AB  - Raman scattering spectra of 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol)
      (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) dispersions, mixed
      with water-soluble porphyrins, i.e. cationic copper(II)-5,10,15,12-tetrakis(4-N
      methylpyridyl) and anionic silver(II)-5,10,15,20-tetrakis(4
      carboxyphenyl)porphyrins, were measured in the 2800-3100 cm(-1) C-H stretching
      vibration region as a function of the temperature within the 5-55 degrees C
      range. Temperature profiles of Raman data were constructed from a quantitative
      data treatment based on factor analysis. This method is shown to be more
      efficient than the commonly used approach employing peak intensity ratios.
      Parameters of the gel phase to liquid crystal phase transition determined from
      Raman temperature profiles were used to monitor the porphyrin influence on DPPG
      and DPPC structures. Both negatively and positively charged porphyrins
      significantly perturb DPPC and DPPG dispersions, causing significant downshift of
      the transition temperature and broadening of the transition region. Water-soluble
      porphyrins are assumed to set at the outside part of phospholipid dispersions and
      interact via coulombic forces with charged lipid heads. For the cationic CuTMPyP,
      the strongest effect has been observed for negatively charged DPPG. In contrast,
      anionic AgTPPC4 has been found to interact more efficiently with DPPC possessing
      both positive and negative charges.

PMID- 15555602
TI  - Effects of non-steroid anti-inflammatory drugs in membrane bilayers.
AB  - The thermal effects of non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam,
      tenoxicam, piroxicam and lornoxicam have been studied in
      dipalmitoylphosphatidylcholine (DPPC) membrane bilayers using neutral and acidic
      environments (pH 2.5). The strength of the perturbing effect of the drugs is
      summarized to a lowering of the main phase transition temperature and a
      broadening of the phase transition temperature as well as broadening or
      abolishment of the pretransition of DPPC bilayers. The thermal profiles in the
      two environments were very similar. Among the NSAIDs studied meloxicam showed the
      least perturbing effect. The differential scanning calorimetry results (DSC) in
      combination with molecular modeling studies point out that NSAIDs are
      characterized by amphoteric interactions and are extended between the polar and
      hydrophobic segments of lipid bilayers. The effects of NSAIDs in membrane
      bilayers were also investigated using Raman spectroscopy. Meloxicam showed a
      gauche:trans profile similar to DPPC bilayers while the other NSAIDs increased
      significantly the gauche:trans ratio. In conclusion, both techniques show that in
      spite of the close structural similarity of the NSAIDs studied, meloxicam appears
      to have the lowest membrane perturbing effects probably attributed to its highest
      lipophilicity.

PMID- 15555603
TI  - Specific interactions of tryptophan with phosphatidylcholine and
      digalactosyldiacylglycerol in pure and mixed bilayers in the dry and hydrated
      state.
AB  - Amphiphilic solutes play an important role in the desiccation tolerance of plant
      cells, because they can reversibly partition into cellular membranes during
      dehydration. Their effects on membrane stability depend on their chemical
      structure, but also on the lipid composition of the host membrane. We have shown
      recently that tryptophan destabilizes liposomes during freezing. The degree of
      destabilization depends on the presence of glycolipids in the membranes, but not
      on the phase preference (bilayer or non-bilayer) of the lipids in mixtures with
      the bilayer lipid phosphatidylcholine. Here, we have investigated the influence
      of tryptophan on the phase behavior and intermolecular interactions in dry and
      hydrated bilayers made from the phospholipid egg phosphatidylcholine and the
      plant chloroplast glycolipid digalactosyldiacylglycerol, or from a mixture (1:1)
      of these lipids, using Fourier-transform infrared spectroscopy. To distinguish
      effects of the hydrophobic ring structure of tryptophan from those of the amino
      acid moiety, we also performed experiments with the hydrophilic amino acid
      glycine. Our data show that there are specific interactions between tryptophan
      and either phospholipid or glycolipid in the dry state, as well as H-bonding
      interactions between the lipids and both solutes. In the rehydrated state, the H
      bonding interactions between amino acids and lipids are mostly replaced by
      interactions between water and lipids, while the hydrophobic interactions between
      lipids and tryptophan mostly persist.

PMID- 15555604
TI  - Characterization of native and oxidized human low-density lipoproteins by the Z
      scan technique.
AB  - The nonlinear optical response of human normal and oxidized by Cu2+ low-density
      lipoproteins particles (LDL), were investigated by the Z-scan technique as a
      function of temperature and concentration of LDL particles. The Z-scan signals
      increase linearly with concentration of normal LDL particles, following the usual
      Beer-Lambert law in a broad range of concentrations. The oxidized LDL particles
      do not show nonlinear optical response. On the other hand, normal LDL increases
      its nonlinear optical response as a function of temperature. These behaviors can
      be attributed to an absorbing element that is modified by the oxidative process.
      Contrarily, changes in the physical state of the cores and conformation of the
      ApoB100 protein due to an increase in temperature seems to enhance their
      nonlinear optical properties. This tendency is not due to aggregation of
      particles. The main contribution to the nonlinear optical response of normal LDL
      particles comes from the phospholipid fraction of the particles.

PMID- 15555605
TI  - Relationship between the action of reactive oxygen and nitrogen species on
      bilayer membranes and antioxidants.
AB  - Membrane lipid peroxidation (LPO) induced by hydroxyl (*OH) and ascorbyl (*Asc)
      radicals and by peroxynitrite (ONOO-) was investigated in asolectin (ASO), egg
      phosphatidylcholine (PC) and PC/phosphatidic acid mixtures (PC:PA) liposomes and
      rat liver microsomes (MC). Enthalpy variation (DeltaH) of PC:PA at different
      molar ratios were obtained by differential scanning calorimetry. It was also
      evaluated the LPO inhibition by quercetin, melatonin and Vitamin B6. The oxidant
      effect power follows the order *OH approximately *Asc > ONOO- on PC and MC;
      whilst on ASO liposomes, it follows *Asc > *OH approximately ONOO-. Increasing
      amounts of PA in PC liposomes resulted in lower levels of LPO. The DeltaH values
      indicate a more ordered membrane arrangement as a function of PA amount. The
      results were discussed in order to provide a complete view involving the
      influence of membranes, oxidants and antioxidants intrinsic behavior on the LPO
      dynamics.

PMID- 15555606
TI  - Favorable and unfavorable lateral interactions of ceramide, neutral
      glycosphingolipids and gangliosides in mixed monolayers.
AB  - Interactions among four natural neutral sphingolipids (ceramide, glucosyl
      ceramide, lactosyl-ceramide and asialo-GM1) and six gangliosides (GM3, GM2, GM1,
      GD3, GD1a and GT1b) were studied in binary Langmuir monolayers at the air-buffer
      interface in terms of their molecular packing, compressibility, dipole potential
      and mixing behavior. The changes of surface organization can be grouped into
      three sets: (a) binary films of neutral GSLs, and of the latter with ceramide,
      exhibit thermodynamically unfavorable mixing with mean molecular area expansions
      and dipole moment hyperpolarization; (b) mixed monolayers of ceramide, or of
      GlcCer, and gangliosides occur with thermodynamically favorable interactions
      leading to mean molecular area condensation and depolarisation; (c) binary
      mixtures of LacCer or Gg4Cer with gangliosides, and all ganglioside species among
      them, revealed molecular immiscibility characterized by additive mean molecular
      area and dipole potential, with composition-independent constant collapse
      pressure. These results disclose basic tendencies of GSLs to molecularly mix or
      demix, leading to their surface segregation, which may underlay vectorial
      separation of their specific biosynthetic pathways.

PMID- 15555607
TI  - Solid-liquid phase behavior of binary fatty acid mixtures 3. Mixtures of oleic
      acid with capric acid (decanoic acid) and caprylic acid (octanoic acid).
AB  - Solid-liquid phase behavior of binary mixtures of oleic acid (OA)/capric acid
      (C10A) and OA/caprylic acid (C8A) were investigated by means of differential
      scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and
      X-ray diffraction. The phase diagram of OA/C10A mixture constructed from the DSC
      results suggested that a molecular compound with the composition of OA:C10A = 3:2
      is formed in a solid phase, and OA and the molecular compound are miscible, while
      C10A and the molecular compound are completely immiscible. The formation of the
      molecular compound was supported by the IR spectroscopic observation, and a
      possible model of the structure was proposed on the basis of X-ray diffraction
      spectrum in small angle region. This compound formation is characteristic of the
      OA/C10A mixture, and may be attributed to the similarity of the acyl chain length
      of C10A to the lengths of Delta- and omega-chains of OA (i.e., the chain segments
      divided by cis-double bond). The mixture of OA and C8A, whose chain length is
      close to but shorter than the two chain segments of OA, provided a eutectic-type
      phase diagram showing a partial mixing of the two components in OA-rich region.
      Thermodynamic analysis of the liquidus line in the phase diagram exhibits a
      systematic trend for the non-ideality parameter of mixing with the variation of
      the chain length difference between OA and saturated fatty acid species.

PMID- 15555608
TI  - Radiation-induced free-radical transformation of phospholipids: MALDI-TOF MS
      study.
AB  - Under the action of free-radical reaction initiators on membrane phospholipids,
      complex processes are taking place in both hydrophobic and hydrophilic parts of
      the phospholipids. Realization of these processes results in a mixture consisting
      of the initial lipids and their peroxidation and fragmentation products.
      Identification of compounds in such mixtures requires analytical methods of high
      sensitivity, reproducibility and accuracy to be applied. These properties are
      characteristic of the matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF MS) method. In the studies of radiation-induced free
      radical transformations of phosphatidylglycerol, the MALDI-TOF MS in combination
      with thin layer chromatography (TLC) has been shown to be able to detect and
      identify products of free-radical transformations taking place in both
      hydrophilic and hydrophobic parts of the phospholipid. Thus, the MALDI-TOF MS can
      serve as a suitable analytical tool to investigate free-radical transformations
      of lipids.

PMID- 15555609
TI  - Native fat globules of different sizes selected from raw milk: thermal and
      structural behavior.
AB  - The aim of this study was to characterize differences in the thermal and
      structural behavior between different sized native milk fat globules. A novel
      microfiltration process permits the selection of native small fat globules (SFG,
      1-3 microm) and large fat globules (LFG, >5 microm) in raw milk, that were
      analyzed by X-ray diffraction (XRD) coupled to differential scanning calorimetry
      (DSC). There were no major differences in triglyceride crystalline structures
      between SFG and LFG, after eliminating thermal history and the influence of
      cooling rates. The three main 3L and 2L crystalline structures appearing under
      slow cooling existed regardless of globule size. The supercooling increased for
      the SFG, mainly due to heterogeneous nucleation in winter milk, and also to
      compositional variations in spring milk. Differences appeared regarding
      stabilized crystalline forms at 20 degrees C and subsequent cooling: the SFG
      contained less 2L triglyceride structures than the LFG. These results can be
      important in dairy manufactures using tempering periods.

PMID- 15555610
TI  - Leptin-resistant obese mice do not form biliary crystals on a high cholesterol
      diet.
AB  - INTRODUCTION: Human obesity is associated with leptin resistance and cholesterol
      gallstone formation. Previously, we demonstrated that leptin-resistant (Lep(db))
      obese mice fed a low cholesterol diet have enlarged gallbladders, but a decreased
      cholesterol saturation index, despite elevated serum cholesterol. Obese humans,
      however, consume a high cholesterol diet. Therefore, we hypothesized that on a
      high cholesterol diet, leptin-resistant mice would have cholesterol saturated
      bile and would form biliary crystals. METHODS: Eight-week old female lean control
      (n = 70) and leptin-resistant (n = 72) mice were fed a 1% cholesterol diet for 4
      weeks. All animals then had cholecystectomies. Bile was collected, grouped into
      pools to determine cholesterol saturation index (CSI), and examined for
      cholesterol crystals. Serum cholesterol and leptin were also measured. RESULTS:
      Gallbladder volumes for Lep(db) mice were enlarged compared with the lean mice
      (35.8 microl versus 19.1 microl, P < 0.001), but the CSI for the Lep(db) mice was
      lower than for the lean animals (0.91 versus 1.15, P < 0.03). The obese animals
      did not form cholesterol crystals, whereas the lean animals averaged 2.2 crystals
      per high-powered field (hpf) (P < 0.001). Serum cholesterol and leptin were also
      elevated (P < 0.001) in the obese animals. CONCLUSIONS: These data suggest that
      Lep(db) obese mice fed a high cholesterol diet have increased gallbladder volume
      and decreased biliary cholesterol saturation and crystal formation despite
      elevated serum cholesterol compared with lean control mice. We conclude that the
      link among obesity, diet, and gallstone formation may not require hypersecretion
      of biliary cholesterol and may be related to the effects of diabetes,
      hyperlipidemia, or both on gallbladder motility.

PMID- 15555611
TI  - Laparoscopic virtual reality training: are 30 repetitions enough?
AB  - BACKGROUND: Current literature suggests that novices reach a plateau after two to
      seven trials when training on the MIST VR laparoscopic virtual reality system. We
      hypothesize that significant benefit may be gained through additional training.
      MATERIALS AND METHODS: Second-year medical students (n = 12) voluntarily enrolled
      under an IRB-approved protocol for MIST VR training. All subjects completed pre-
      and posttraining questionnaires and performed 30 repetitions of 12 tasks.
      Performance data were automatically recorded for each trial. Learning curves for
      each task were generated by fitting spline curves to the mean overall scores for
      each repetition. Scores were assessed for plateaus by repeated measures, slope,
      and best score. RESULTS: On average, subjects completed training in 7.1 h.
      (range, 5.9-9.2). Two to seven performance plateaus were identified for each of
      the 12 MIST VR tasks. Initial plateaus were found for all tasks by the 8th
      repetition; however, ultimate plateaus were not reached until 21-29 repetitions.
      Overall best score was reached between 20 and 30 repetitions and occurred beyond
      the ultimate plateau for 9 tasks. CONCLUSIONS: These data indicate that a lengthy
      learning curve exists for novices and may be seen throughout 30 repetitions and
      possibly beyond. Performance plateaus may not reliably determine training
      endpoints. We conclude that a significant and variable amount of training may be
      required to achieve maximal benefit. Neither a predetermined training duration
      nor an arbitrary number of repetitions may be adequate to ensure laparoscopic
      proficiency following simulator training. Standards which define performance
      based endpoints should be established.

PMID- 15555612
TI  - Effects of ceftriaxone sodium on in vitro gallbladder contractility in guinea
      pigs.
AB  - BACKGROUND/PURPOSE: It has been reported that ceftriaxone may induce the
      formation of gallstones. Changes of gallbladder motility may play a role in this
      phenomenon. The present study was designed to analyze the gallbladder
      contractility of ceftriaxone sodium-treated guinea pigs in response to different
      agonists. MATERIALS AND METHODS: Twenty adult guinea pigs were randomly divided
      into two groups. Ten guinea pigs were treated with ceftriaxone sodium (100
      mg/kg/day) for 10 days, whereas the remaining 10 served as the control group,
      receiving 1 ml of distilled water during 10 days as placebo. By the end of the
      experimental period the animals were sacrificed and the gallbladders were
      removed. The responses to KCl, papaverine, sodium nitroprusside, carbachol, and
      histamine on gallbladder strips from control and experimental groups were
      recorded and analyzed. RESULTS: There was no significant difference between the
      responsiveness to KCl, papaverine, and sodium nitroprusside on tissues isolated
      from experimental and control groups. Comparison of the two groups revealed that
      the maximum responses (E(max)) to carbachol and histamine were significantly
      reduced in the experimental group, without any change in the pD(2) values.
      CONCLUSION: These data indicate that, after ceftriaxone sodium therapy, the
      decreased maximum contractile response to carbachol and histamine may contribute
      to the formation of gallstones.

PMID- 15555613
TI  - Errors and adverse outcomes on a surgical service: what is the role of residents?
AB  - PURPOSE: The extensive changeover in residents that occurs every July in
      university-affiliated hospitals has been postulated to result in impaired
      delivery of patient care as new house staff are less experienced and unfamiliar
      with hospital-specific systems (the "July phenomenon"). To assess the impact of
      this process on patient safety, we examined the incidence and sources of medical
      error and adverse outcomes on a pediatric general surgery service during the
      final month of an academic year and the first month of the subsequent academic
      year. MATERIALS AND METHODS: All admissions to two pediatric surgeons during June
      and July 2002 were prospectively followed. The attending surgeon, a surgical
      fellow, and a medical student reviewed in-patient care daily. Errors committed by
      doctors, nurses, and allied health workers were identified through daily patient
      encounters, nursing rounds, medical rounds, and chart audit. Adverse outcomes
      were evaluated based on type and contributing factors, including involvement of
      residents. To correct for variations in patient volume, the incidence of errors
      and adverse outcomes were expressed as a percentage of total patient days.
      RESULTS: The error rate was 46/643 patient days (7.1%) in June, and 58/776
      patient days (7.5%) in July (P = 0.9). Resident error accounted for 52.2% of
      errors in June and 39.7% of errors in July (P = 0.28). There was no significant
      difference in the adverse outcome rates (5% versus 6.7%, P = 0.21) or incidence
      of error-related adverse outcomes (10.8% versus 22.4%, P = 0.2) between June and
      July. Most errors were made by the on-call resident. CONCLUSION: Resident
      changeover at the completion of an academic year did not result in an increased
      number of medical errors or adverse outcomes, indicating that effective systems
      are in place to prevent the "July phenomenon."

PMID- 15555614
TI  - Differential regulation of ERK1/2 and p38(MAPK) by components of the Rho
      signaling pathway during sphingosine-1-phosphate-induced smooth muscle cell
      migration.
AB  - OBJECTIVE: To determine the role of rhosignaling in sphingosine-1-phosphate (S-1
      P)-induced smooth muscle cell migration. BACKGROUND: S-1-P is a bioactive
      sphingolipid released from activated platelets stimulating migration of smooth
      muscle cells (SMC) in vitro through Galphai G-proteins and MAPK activation. Rho
      is one of the key small GTPases required for cytoskeletal reorganization and MAPK
      activation during migration. We hypothesized that S-1-P-stimulated migration is
      regulated by the rho-signaling pathway. METHODS: Rat arterial SMCs were cultured
      in vitro. Linear wound assays of migration were performed in the presence of S-1
      P with and without C3 (a rho antagonist) and Y (Y27632, a Rho kinase inhibitor).
      Western blotting was performed for MEK1-ERK1/2 and MMK3/MKK6-p38(MAPK)
      phosphorylation after stimulation with S-1-P with and without pre-incubation with
      the inhibitors. Statistics were analyzed by one-way ANOVA. RESULTS: S-1-P
      stimulated migration of SMCs in a wound assay (2-fold over control; P < 0.01),
      which was blocked by Rho inhibition (P < 0.05). S-1-P activated rho and induced a
      time-dependent increase in ERK1/2 and p38(MAPK) activation. In the presence of
      C3, MEK1 and ERK1/2 phosphorylation were significantly decreased, while MKK3/6
      and p38(MAPK) phosphorylation were unchanged. In contrast, when rho kinase was
      inhibited, there was an increase in ERK1/2 and a decrease in p38(MAPK)
      phosphorylation. Rho kinase inhibition resulted in a decrease in MEK1/2 and
      MKK3/6 phosphorylation. CONCLUSIONS: S-1-P differentially regulates the MAPK
      pathway through components of the rho pathway. Rho regulates ERK1/2 activation
      through MEK1/2, while Rho kinase negatively modulates ERK1/2 in a MEK1/2
      independent manner and regulates p38(MAPK) through MKK3/6. This is the first
      description of differential MAPK regulation by a G-protein-coupled receptor
      through the rho pathway. Understanding signal transduction in SMCs will
      contribute to the development of molecular therapeutics for intimal hyperplasia.

PMID- 15555615
TI  - Albumin impacts the effects of tonicity on microvascular hydraulic permeability.
AB  - BACKGROUND: An increase in tonicity shrinks endothelial cells. This cell
      shrinkage may open inter-endothelial gaps and allow more fluid to escape from the
      microvasculature. This increase in microvascular permeability is not supported by
      clinical studies suggesting that water is pulled into the vascular space, not
      lost into the interstitium. We hypothesized that albumin influences the change in
      trans-endothelial water movement caused by alterations in tonicity by a mechanism
      other than oncotic pressure. MATERIALS AND METHODS: Hydraulic permeability (L(p))
      was measured in rat mesenteric venules using the Landis micro-occlusion model.
      Measures of L(p) were obtained after successive perfusions with 1% albumin
      solution (BSA) of varying sodium chloride (NaCl) concentrations (85, 135, 185,
      and 235 mm) (n = 6). Additional venules were perfused with 7% NaCl followed by 7%
      NaCl + BSA and L(p) measured (n = 6). Units for L(p) are x10(-7) cm/sec(-1)
      cm/H(2)O(-1). RESULTS: As the NaCl concentration in BSA increased from 85 mm to
      235 mm, L(p) decreased from 1.93 +/- 0.41 to 0.97 +/- 0.11. Compared to results
      without albumin, BSA with 185 mm NaCl decreased L(p) from 3.93 +/- 0.08 to 1.25
      +/- 0.18 (P = 0.04), and BSA with 235 mm NaCl decreased L(p) from 6.14 +/- 0.05
      to 0.96 +/- 0.11 (P = 0.002). There was a three-fold decrease in L(p) when BSA
      was added to the 7% NaCl solution (P = 0.02). CONCLUSIONS: Albumin attenuated the
      increase in L(p) that is associated with higher NaCl concentrations. Because this
      model controls for oncotic pressure, albumin may impact L(p) by a mechanism other
      than oncotic force. Albumin appears to stabilize the endothelial barrier during
      HS perfusion and prevents the loss of intravascular fluid. Appropriate albumin
      levels may play an important clinical role in modulating trans-endothelial fluid
      efflux during HS administration.

PMID- 15555616
TI  - Correlation of plasma and tissue oxidative stresses in intra-abdominal sepsis.
AB  - BACKGROUND: The aim of this study was to investigate the correlation between
      plasma and tissue oxidative stress and the antioxidative response, by measuring
      malon dialdehyde (MDA) and glutathione (GSH) in late sepsis induced by cecal
      ligation and perforation. MATERIALS AND METHODS: A prospective, randomized,
      controlled experimental study in rats was done. Forty rats, weighing 200-250 g,
      were randomly divided into two groups (n = 20). In group 1, laparotomy was
      performed under aseptic conditions, and the cecum ligated and perforated. The
      abdomen was closed. In group 2, sham control, there was only laparotomy. Twenty
      four hours later, blood samples were taken by cardiac puncture for plasma MDA and
      GSH, followed by harvesting of samples from lung, liver, kidney, and heart in
      both groups. RESULTS: In the liver, lung, plasma, heart, and kidney, MDA
      concentrations were increased in the sepsis group after 24 h (P < 0.001 for all
      organ samples). In the same organs, GSH concentrations were decreased by sepsis
      (P < 0.001 for all organ samples). In both groups, plasma MDA was positively
      correlated to MDA in heart (r = 0.82, P < 0.001), liver (r = 0.76, P < 0.001),
      lung (r = 0.78, P < 0.001), and kidney (r = 0.73, P < 0.001). Similarly, plasma
      GSH was positively correlated to GSH in liver (r = 0.93, P < 0.001), heart (r =
      0.86, P < 0.001), lung (r = 0.91, P < 0.001), and kidney (r = 0.79, P < 0.001).
      CONCLUSIONS: Plasma MDA and GSH were positively correlated with tissue MDA and
      GSH in intra-abdominal sepsis in a rat model.

PMID- 15555617
TI  - Prediction of lymph node metastasis and perineural invasion of biliary tract
      cancer by selected features from cDNA array data.
AB  - OBJECTIVE: To better understand the nature of the malignancy of biliary tract
      carcinoma and evaluate the feasibility of its prediction by gene expression
      profiles. METHODS AND RESULTS: We explored the gene expression profiles
      characteristic of progression and invasiveness in the cDNA array data obtained
      from 37 biliary tract carcinomas (15 bile duct, 11 gallbladder, 11 of ampulla of
      Vater). We pre-selected 51 and 100 genes for the presence versus absence of lymph
      node metastasis and perineural invasion on the basis of statistical difference.
      To search optimized sets of genes for prediction, we applied a sequential forward
      feature selection, minimizing leave-one-out error rates on a k-nearest neighbor
      classifier. We could predict lymph node metastasis and perineural invasion with
      an accuracy of 94 and 100%, respectively. When the 6-stage IA cancers without
      perineural invasion were precluded, a marked difference in gene expression (147
      gene), discriminable with 100% accuracy, was noted between positive versus
      negative perineural invasion, suggesting that the acquisition of invasive
      character is rather a later molecular pathological event in biliary tract cancer.
      CONCLUSION: The present method provides a powerful means of classifying biliary
      tract carcinomas. We also suggest that perineural invasion is an important target
      of array databased pattern classification, which may predict patient outcomes and
      facilitate the determination of the extent of surgery to minimize the risk of
      recurrence.

PMID- 15555618
TI  - Measuring platelet aggregation to estimate small intestinal ischemia-reperfusion
      injury.
AB  - BACKGROUND: The success of intestinal transplantation is affected by the extreme
      susceptibility of the small bowel to ischemia-reperfusion (I/R) injury.
      Currently, there is no quick, convenient method to estimate the extent of small
      bowel I/R injury. Although histological evaluation is reliable and accurate, it
      takes too long to allow favorable intervention in I/R injury. I/R causes the
      production of arachidonic acid products, oxygen free radicals, cytokines, and
      nitric oxide, which affect platelet function. OBJECTIVE: This study determined
      whether measuring platelet aggregation is useful for evaluating small bowel I/R
      injury. METHODS: Eighteen mongrel dogs were divided into three groups. In group A
      both the superior mesenteric artery (SMA) and vein (SMV) were occluded for 120
      min. In group B the SMA was occluded for 60 min. Group C underwent a sham
      operation. Platelet aggregation was measured using a whole blood aggregometer
      (WBA analyzer), which readily handles small samples. Histological examination was
      performed. The correlation between platelet aggregation and histology was
      analyzed. RESULTS: Platelet aggregation was similar in all groups before
      reperfusion. After reperfusion, platelet aggregation was significantly lower in
      group A than in groups B and C (P < 0.05), and mucosal damage was most severe in
      group A (P < 0.05). After 1 and 3 h of reperfusion, there was a significant
      negative correlation between platelet aggregation and histological damage.
      CONCLUSIONS: Measuring platelet aggregation is rapid, easy, and useful for
      evaluating small bowel I/R injury.

PMID- 15555620
TI  - IL-12 cDNA direct injection: antimetastatic effect from a single injection in a
      murine hepatic metastases model.
AB  - BACKGROUND: Interleukin 12 (IL-12) gene therapy is an effective antitumor agent
      in local and metastatic murine tumor models. We sought to evaluate the
      antimetastatic effect of IL-12 cDNA in a liver metastases model. MATERIALS AND
      METHODS: A liver metastases model was induced by creating a "primary" splenic
      tumor through inoculation of 1 x 10(5) TS/A adenocarcinoma cells directly into
      the inferior pole of the spleen in female BALB/c mice. On day 4, 50 microg of IL
      12 cDNA or control plasmid DNA was injected into splenic tumor, followed by
      splenectomy on day 8. Mice were sacrificed on day 25 to assess liver tumor
      burden. IL-12 mRNA and mIL-12 and IFN-gamma protein levels were assessed after IL
      12 injection. Peripheral blood CD4+, CD8+, and NK cells were quantified on day 14
      using FACS. To determine the significance of site of cytokine DNA injection, IL
      12 cDNA was injected on day 4 into splenic tumor or into the non-involved spleen
      after isolation of the inferior and superior portions of the spleen,
      respectively, with surgical clips. Splenectomy was performed on day 8 and
      sacrifice was performed on day 25. RESULTS: IL-12 mRNA was detected in the liver
      8 h after injection, with a peak at 24 h. After splenic injection, protein levels
      of IL-12 and IFN-gamma were detectable in the liver and spleen 24 h after
      treatment. IL-12 and IFN-gamma were not detectable in control animals. In the
      peripheral blood, there was a marked increase in NK cells (13% of total
      lymphocytes versus 4%, control) and in the CD4+/CD8+ ratio (5.5 versus 1.9). At
      day 25, there was a marked antimetastatic effect after IL-12 injection into
      either splenic tumor [liver:body weight, 6.2 versus 10.9 (control), P = 0.007] or
      non-involved spleen (6.8 g versus 10.7 g, P = 0.005). There was no difference in
      the antimetastatic effect between animals injected into splenic tumor or non
      involved spleen (P = 0.3). CONCLUSION: Injection with a single dose of IL-12 cDNA
      into splenic tumor or non-involved spleen resulted in a profound antimetastatic
      effect. Splenic IL-12 injection results in mRNA expression in the liver, protein
      expression in the liver and spleen, and a marked increase in NK cells and the
      CD4+/CD8+ ratio in peripheral blood.

PMID- 15555619
TI  - Acute pancreatitis induces FasL gene expression and apoptosis in the liver.
AB  - BACKGROUND: Liver injury is an important prognostic indicator in acute
      pancreatitis. We previously demonstrated that Kupffer cell-derived cytokines
      mediate liver injury. In this work, we sought to characterize the role of Fas
      Ligand (FasL) in liver injury during acute pancreatitis. METHODS: Acute
      pancreatitis was induced in mice using cerulein; serum FasL, AST, ALT, liver
      FasL, p38-MAPK, and caspase-3 were measured. FasL mRNA and protein and its
      receptor (Fas) were determined in rat Kupffer cells treated with elastase (1
      U/ml) to mimic acute pancreatitis. Apoptosis was measured by flow cytometry.
      RESULTS: Cerulein-induced pancreatitis increased serum AST, ALT, and FasL and up
      regulated liver FasL (1315 +/- 111 versus 310 +/- 164 pg/ml, P = 0.002 versus
      sham), while inducing p38-MAPK phosphorylation (P < 0.01 versus sham) and
      cleavage of caspase-3 (P < 0.04 versus sham); all were attenuated by pretreatment
      with the Kupffer cell inhibitor, gadolinium (all P < 0.003). In vitro, elastase
      induced a time-dependent increase in Kupffer cell FasL protein (FasL = 404 +/- 94
      versus 170 +/- 40, P = 0.02, versus control), a 100-fold increase in FasL mRNA,
      and up-regulated Fas (FasL receptor). Gadolinium significantly attenuated the
      elastase-induced increase in FasL and FasL mRNA (FasL = 230 +/- 20 versus 404 +/-
      94, P = 0.01, versus elastase) but had little effect on Fas. Additionally,
      elastase-primed Kupffer cell media induced apoptosis in hepatocytes (29 +/- 1
      versus 16% +/- 1%; versus control, P < 0.001). CONCLUSIONS: Acute pancreatitis
      induces liver injury and hepatocyte death while up-regulating FasL, p38-MAPK, and
      caspase-3. Fas is up-regulated within Kupffer cells, suggesting that FasL may
      autoregulate its production by inducing its originator-cell death. The ability to
      manipulate interactions between Kupffer cells and hepatocytes may have important
      therapeutic implications.

PMID- 15555621
TI  - The efficacy of fibrin sealant in prevention of anastomotic leak after
      laparoscopic gastric bypass.
AB  - BACKGROUND: Anastomotic leak after laparoscopic gastric bypass (GBP) can result
      in significant morbidity, mortality, and consumption of healthcare resources.
      Fibrin sealant has been used clinically in the prevention of leak; however, its
      efficacy has not been clearly demonstrated. The aims of this study were to (1)
      develop an iatrogenic leak model in swine, (2) examine the efficacy of fibrin
      sealant in sealing iatrogenic anastomotic leak, and (3) review our experience
      with the use of fibrin sealant in 66 patients who underwent laparoscopic GBP.
      METHODS: This study was performed in three phases. In phase 1, laparoscopic
      gastrojejunostomy was performed in adult swine with iatrogenic disruption of the
      anastomotic staple line. The size of disruption was sequentially increased (6- to
      12-F opening) until a leak model was developed. In phase 2, 16 animals underwent
      laparoscopic gastrojejunostomy with a 12-F disruption of the anastomosis; 10
      animals (study group) had fibrin sealant (Tisseel VH) applied on the disrupted
      anastomosis and 6 animals (control group) did not receive fibrin sealant. Animals
      were sacrificed on postoperative day 5 or earlier if peritonitis developed and
      were examined for sealing of the anastomotic disruption and the presence of
      intraabdominal abscess. In phase 3, the outcome of 66 consecutive patients who
      underwent laparoscopic GBP with fibrin sealant applied at the gastrojejunostomy
      was reviewed. RESULTS: In phase 1, an anastomotic leak model was developed with a
      12-F disruption of the staple line. In phase 2, two control animals required
      early sacrifice for bile peritonitis; three control animals had intraabdominal
      abscess discovered at sacrifice and one animal did not have any evidence of
      intraabdominal abscess or leak. Of the 10 animals in the study group, all
      survived until sacrifice and none of these animals had evidence of intraabdominal
      abscess or persistent leak. Therefore, 83% of animals in the control group
      developed either leak or abscess compared to 0% in the study group (P < 0.01,
      Fisher's exact test). Clinically, no leak or intraabdominal abscess developed in
      66 patients who underwent laparoscopic GBP with the use of fibrin sealant.
      CONCLUSIONS: An anastomotic leak model was developed in swine with disruption of
      the stapled gastrojejunostomy to a 12-F opening. The use of fibrin sealant
      significantly reduces leak and abscess complication. Our results support the
      tissue sealing property of fibrin sealant and its use on high-risk
      gastrointestinal anastomosis.

PMID- 15555622
TI  - Validation of bioluminescence imaging of colorectal liver metastases in the
      mouse.
AB  - BACKGROUND: In mouse models for metastatic growth of colorectal carcinoma (CRC)
      cells in the liver, tumor growth is routinely measured by determining the area of
      liver tissue that has been replaced by tumor tissue (hepatic replacement area
      [HRA]). This technique has several major disadvantages. Modern visualization
      techniques make it possible to image tumor growth noninvasively. In the present
      report, we validated bioluminescence imaging of liver metastases by comparing it
      to standard HRA measurements and liver weight. MATERIALS AND METHODS: BALB/c mice
      received an intrasplenic injection of luciferase-expressing C26 CRC cells and the
      spleen was subsequently removed. On days 5, 7, 9, and 11 after injection,
      luciferase activity was measured. After imaging, the mice were sacrificed and the
      livers was removed, weighed, and fixed. HRA was determined by analyzing liver
      tissue sections. Comparative trend analyses between luciferase activity, wet
      liver weight, and HRA were then performed. RESULTS: Luciferase activity, wet
      liver weight, and HRA all increased over time. Statistical analyses showed that
      all three types of measurements display a highly significant degree of
      correlation. CONCLUSIONS: The measurement of tumor growth in the liver by imaging
      luciferase activity correlates well with the standard method of determining the
      HRA and with the increase in liver weight that results from tumor growth. Given
      the great advantages of measuring luciferase activity over measuring HRA, we
      conclude that bioluminescent imaging is a reliable and superior method for
      measuring experimental CRC growth in the liver.

PMID- 15555623
TI  - Nuclear factor-kappa B and apoptosis inducing factor activation by doxorubicin
      analog WP744 in SH-SY5Y neuroblastoma cells.
AB  - BACKGROUND: Neuroblastoma (NB) is one of the most common extracranial tumors in
      children. The chemotherapeutic doxorubicin (Dox) remains a mainstay for
      treatment. However, the emergence of drug resistance seriously limits treatment
      efficacy. Numerous Dox analogues have been designed to more potently kill drug
      naive as well as drug-resistant NB. We have shown that the Dox analogue WP744 has
      enhanced the killing activity of NB compared to Dox, but the mechanism(s) of
      action is unclear. MATERIALS AND METHODS: MTT assays were used to characterize
      the relative potencies of Dox and WP744 against SH-SY5Y NB cells. Western
      blotting was used to assess activation of caspases-3, -9, anti-poly (ADP-ribose)
      polymerase, p53, p21, AIF, IkappaBalpha, Bcl-2, Bcl-X(L), and cyclin D1. Nuclear
      factor (NF-kappaB) activation was assessed by electrophoretic mobility shift
      assay. RESULTS: After WP744 treatment, enhanced apoptosis and cell death were
      seen, associated with cleavage of caspases-3, -9, and anti-poly (ADP-ribose)
      polymerase, an increase in p53 protein levels, and the induction of p21. WP744
      also induced translocation of apoptosis-inducing factor from mitochondria to
      nuclei. Most remarkably, WP744 was 50-fold more potent than Dox in activating NF
      kappaB. WP744 treatment also resulted in the down-regulation of expression of
      downstream targets of NF-kappaB. CONCLUSIONS: WP744 is a novel Dox analogue that
      triggers apoptosis and cell killing by activation of proapoptotic mediators in NB
      cells. Enhanced cytotoxicity of this novel drug compared with Dox may be related
      to more effective activation of NF-kappaB and apoptosis-inducing factor in tumor
      cells.

PMID- 15555624
TI  - Videoendoscopic endotracheal intubation in the rat: a comprehensive rodent model
      of laparoscopic surgery.
AB  - BACKGROUND: Peritoneal absorption of CO(2) during abdominal insufflation in
      laparoscopy may disrupt the acid-base equilibrium and alter the physiological
      response to stress. Current nonventilated rodent models of laparoscopy do not
      manage the CO(2) load of pneumoperitoneum, but ventilated surgical rodent models
      are invasive (tracheotomy) and may independently induce the inflammatory
      response. MATERIALS AND METHODS: A comprehensive rodent model of laparoscopy was
      developed. Rats were randomized to receive anesthesia alone, anesthesia plus
      CO(2) pneumoperitoneum, or anesthesia plus CO(2) pneumoperitoneum with
      videoendoscopic intubation and mechanical ventilation. Arterial blood-gas
      analysis was performed at baseline and after 30 min of intervention. RESULTS:
      Baseline pH, pCO(2), and HCO(3)(-) arterial blood gas parameters were normal for
      all rats. After 30 min, pCO(2) and pH changed slightly but remained normal among
      rats receiving anesthesia alone (pCO(2) = 46.5 +/- 1.9; pH = 7.365 +/- 0.009)
      whereas animals receiving anesthesia plus CO(2) pneumoperitoneum that were
      dependent on spontaneous respiration for ventilation developed significant
      hypercarbic acidosis (pCO(2) = 53.2 +/- 1.9, P < 0.05; pH = 7.299 +/- 0.011, P <
      0.001). This acidosis was completely corrected with increased minute ventilation
      in intubated rats receiving mechanical ventilation (pCO(2) = 36.8 +/- 1.5, P <
      0.001; pH = 7.398 +/- 0.011, P < 0.001). CONCLUSIONS: CO(2) pneumoperitoneum
      induces significant hypercarbic acidosis in nonventilated rats. Noninvasive
      endotracheal intubation is feasible in the rat with videoendoscopic assistance.
      Our noninvasive rodent model of laparoscopic surgery controls for anesthesia- and
      capnoperitoneum-related acid-base changes and provides an environment in which
      the biological response to pneumoperitoneum can be studied precisely.

PMID- 15555625
TI  - Expression and regulation of neuropilins and VEGF receptors by TNF-alpha in human
      endothelial cells.
AB  - BACKGROUND: Recently, neuropilins (NRPs) were identified as new VEGF receptors
      (VEGFRs) and VEGFR-3 was revealed to be implicated in angiogenesis besides in
      lymphangiogenesis. However, quantitative expression and regulation of NRPs and
      VEGFRs remain unclear. The objective of this study was to compare the expression
      of NRPs and VEGFRs and investigate their regulation by tumor necrosis factor (TNF
      alpha) in human endothelial cells (ECs) as well as their roles in VEGF(165)
      induced EC proliferation. MATERIALS AND METHODS: Human umbilical vein ECs
      (HUVECs) were treated with TNF-alpha (2 ng/ml) or PBS for 24 h. The mRNA and
      protein levels of NRP-1, NRP-2, VEGFR-1, VEGFR-2, and VEGFR-3 were
      semiquantitatively determined by real-time PCR and Western blot, respectively.
      Real-time PCR data were presented as the difference of reaction cycle thresholds
      (Ct) between beta-actin and each of the genes of interest (2(-DeltaCt)). EC
      proliferation in response to VEGF(165) (10 ng/ml) with or without anti-VEGFR-2
      neutralization antibody pretreatment was analyzed by [(3)H]thymidine
      incorporation. RESULTS: In PBS-treated HUVECs, mRNA levels of NRPs and VEGFRs
      were NRP-1 (0.013), NRP-2 (0.007), VEGFR-2 (0.006), VEGFR-1 (0.0024), and VEGFR-3
      (0.0009). After TNF-alpha treatment, mRNA levels of VEGFR-2, VEGFR-3, and NRP-1
      were significantly reduced by 72, 65, and 53%, respectively (P < 0.05). The
      protein expression of all NRPs and VEGFRs were also detected by Western blot. TNF
      alpha significantly reduced protein levels of VEGFR-2, VEGFR-3, and NRP-1 by 59,
      35, and 22%, respectively. However, both mRNA and protein levels of VEGFR-1 and
      NRP-2 were not affected by TNF-alpha. Furthermore, TNF-alpha treatment
      significantly reduced EC proliferation in response to VEGF(165) by 67%. After
      blocking VEGFR-2 with neutralization antibody, TNF-alpha treatment elicited a 30%
      reduction of EC proliferation in response to VEGF(165). CONCLUSIONS: These data
      demonstrate that HUVECs express higher mRNA levels of NRP-1 and NRP-2 than those
      of VEGFRs, and TNF-alpha treatment significantly decreases the expression of
      VEGFR-2, VEGFR-3, and NRP-1, which may be responsible for TNF-alpha-induced
      reduction of EC proliferation in response to VEGF(165).

PMID- 15555626
TI  - Oral arginine reduces gut mucosal injury caused by lipopolysaccharide endotoxemia
      in rat.
AB  - BACKGROUND: The objective of this study was to evaluate the effects of
      lipopolysaccharide (LPS) endotoxemia and enteral arginine (ARG) supplementation
      on intestinal structural changes, enterocyte proliferation, and apoptosis in rat.
      METHODS: Male Sprague-Dawley rats, weighing 250-280 g, were divided into three
      experimental groups: control rats, LPS rats treated with lipopolysaccharide given
      ip at a dose of 10 mg/kg every 24 h (two injections), and LPS-ARG rats treated
      with enteral arginine given in drinking water (2%) 72 h before and following
      injection of LPS. Intestinal structural changes, enterocyte proliferation, and
      enterocyte apoptosis were determined on day 3 following the first LPS injection.
      RESULTS: LPS rats demonstrated a significant decrease in bowel weight in
      duodenum, mucosal weight in duodenum, jejunum, and ileum, mucosal DNA and protein
      in jejunum and ileum, and villus height in jejunum and ileum compared to control
      animals. LPS rats also had a significantly lower cell proliferation index in
      jejunum and ileum and a higher apoptotic index in jejunum and ileum compared to
      control rats. LPS-ARG animals demonstrated greater duodenal bowel weight,
      duodenal and ileal mucosal weight, ileal mucosal DNA and protein, ileal villus
      height, and jejunal and ileal cell proliferation index compared to LPS animals.
      CONCLUSIONS: LPS endotoxemia impairs the integrity of the gastrointestinal mucosa
      in rat. Decreased cell proliferation and increased apoptosis may be considered
      the main mechanisms responsible for the decreased cell mass. Enteral arginine
      administration decreases the mucosal injury caused by lipopolysaccharide.

PMID- 15555627
TI  - Active-site inactivated FVIIa decreases thrombosis and necrosis in a random skin
      flap model of acute ischemia.
AB  - BACKGROUND: Previous studies have emphasized the role of ischemia in inducing
      vascular thrombosis. MATERIALS AND METHODS: Using a skin flap model of acute
      ischemia in the rat, we studied the effect of active-site inactivated factor VIIa
      (FVIIai), an inhibitor of tissue factor (TF), on tissue survival during acute
      ischemia. RESULTS: Ribonuclease protection analysis revealed an increase in TF in
      ischemic parts of the flap, and in situ hybridization localized this increase
      mainly to perivascular cells. A decrease in vascular thrombosis, as determined by
      fibrin immunostaining, was observed in FVIIai-treated animals. Intravenous
      administration of FVIIai had a positive impact on survival of the flap. Laser
      Doppler flowmetry revealed an increase in blood flow in the FVIIai-treated group.
      In treated animals, prothrombin time (PT) was increased (P < 0.01), whereas
      partial thromboplastin time (APTT) was unaltered; no significant impairment in
      systemic hemostasis (peri- and postoperative bleeding) was observed. CONCLUSIONS:
      These findings demonstrate that TF expression is increased in perivascular cells
      in ischemic skin flaps and that FVIIai, by inhibiting TF, increases flap
      survival.

PMID- 15555628
TI  - Lipopolysaccharide suppresses albumin expression by activating NF-kappaB in rat
      hepatocytes.
AB  - BACKGROUND: The severity of hypoalbuminemia has been shown to be related to
      morbidity and mortality in critical illness, illustrating the need for better
      understanding of the molecular mechanism of hypoalbuminemia.
      Lipopolysaccharide(LPS) is a key mediator which induces hypoalbuminemia in sepsis
      and septic shock. The present studies were performed to identify whether the
      reduction of albumin expression induced by LPS was mediated by activating nuclear
      factor kappa B(NF-kappaB) in cultured rat hepatocytes. MATERIALS AND METHODS:
      Primary rat hepatocytes were divided into five groups treated with normal saline
      or 1 ng/ml, 0.01 microg/ml, 0.1 microg/ml, or 1 microg/ml of LPS for 24 h. The
      albumin level in the supernatant and NF-kappaB activity in hepatocytes were
      measured. Hepatocytes were pretreated for 30 min with SN50 (a highly selected
      inhibitor of NF-kappaB) at different concentrations (10, 30, and 50 microg/ml).
      After 24 h of treatment with 1 microg/ml of LPS, the culture medium was measured
      for albumin level. Meanwhile, NF-kappaB activity in hepatocytes was assayed.
      RESULTS: LPS dramatically decreased albumin expression and enhanced NF-kappaB
      activity in rat hepatocytes, especially in the 1 microg/ml LPS group. This
      reduction in albumin expression induced by LPS can be completely inhibited by
      SN50 in different concentrations, and the maximal increase in albumin was
      observed at a SN50 dosage of 30 microg/ml. CONCLUSIONS: The results suggest that
      LPS inhibits albumin expression by activating NF-kappaB signaling. NF-kappaB is a
      critical signaling pathway in LPS-induced hypoalbuminemia which it is worthwhile
      to understand in studying the molecular mechanism of hypoalbuminemia in sepsis
      and septic shock.

PMID- 15555629
TI  - Stem cells in modern medicine: reality or myth?

PMID- 15555630
TI  - Dynamism of GABA(A) receptor activation shapes the "personality" of inhibitory
      synapses.
AB  - The kinetics of synaptic currents is largely determined by the postsynaptic
      receptor gating and the concentration time course of synaptic neurotransmitter.
      While the analysis of current responses to rapid agonist application provides the
      means to study the ligand-gated receptor gating, no direct tools are available to
      measure the neurotransmitter transient at GABAergic and glutamatergic synapses.
      Several lines of evidence indicate that the synaptic agonist transient is very
      brief suggesting that the activation of postsynaptic receptors occurs in
      conditions of extreme non-equilibrium. Such a dynamic pattern of activation has a
      crucial impact not only on the kinetics of synaptic currents but also on their
      susceptibility to pharmacological modulation. Thus, changes in the synaptic
      agonist waveform due to, for example modulation of the release machinery or
      uptake system may considerably alter both kinetics and pharmacology of synaptic
      currents. The use of modifiers of GABA(A) receptor gating and low-affinity
      antagonists provides a tool to estimate the time course of the agonist transient
      revealing that synaptic neurotransmitter is not saturating and that the agonist
      clearance occurs at a sub-millisecond time scale. It is proposed that dynamic
      conditions of synaptic receptor activation assure a broad spectrum of performance
      rendering the synapse extremely susceptible to a variety of modulatory processes.

PMID- 15555631
TI  - JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor
      antagonist.
AB  - We examined the pharmacological profile of (3,4-dihydro-2H-pyrano[2,3]b quinolin
      7-yl) (cis-4-methoxycyclohexyl) methanone (JNJ16259685). At recombinant rat and
      human metabotropic glutamate (mGlu) 1a receptors, JNJ16259685 non-competitively
      inhibited glutamate-induced Ca2+ mobilization with IC50 values of 3.24+/-1.00 and
      1.21+/-0.53 nM, respectively, while showing a much lower potency at the rat and
      human mGlu5a receptor. JNJ16259685 inhibited [3H]1-(3,4-dihydro-2H-pyrano[2,3
      b]quinolin-7-yl)-2-phenyl-1-ethanone ([3H]R214127) binding to membranes prepared
      from cells expressing rat mGlu1a receptors with a Ki of 0.34+/-0.20 nM.
      JNJ16259685 showed no agonist, antagonist or positive allosteric activity toward
      rat mGlu2, -3, -4 or -6 receptors at concentrations up to 10 microM and did not
      bind to AMPA or NMDA receptors, or to a battery of other neurotransmitter
      receptors, ion channels and transporters. In primary cerebellar cultures,
      JNJ16259685 inhibited glutamate-mediated inositol phosphate production with an
      IC50 of 1.73+/-0.40 nM. Subcutaneously administered JNJ16259685 exhibited high
      potencies in occupying central mGlu1 receptors in the rat cerebellum and thalamus
      ( ED50=0.040 and 0.014 mg/kg, respectively). These data show that JNJ16259685 is
      a selective mGlu1 receptor antagonist with excellent potencies in inhibiting
      mGlu1 receptor function and binding and in occupying the mGlu1 receptor after
      systemic administration.

PMID- 15555632
TI  - Effects of MPEP on locomotion, sensitization and conditioned reward induced by
      cocaine or morphine.
AB  - Exposure to environmental cues is considered a major cause of relapse in
      detoxified addicts. Recent findings showed an involvement of glutamate in cue
      induced relapse and suggest that subtype 5 of metabotropic glutamate receptors
      (mGluR5) is involved in conditioned drug-reward. The present study applied the
      conditioned place preference (CPP) paradigm to examine the involvement of mGluR5
      in cocaine- and morphine-induced behaviours. Results of previous mice-studies
      were extended into rats by using the selective mGluR5 antagonist 2-methyl-6
      (phenylethynyl)pyridine (MPEP). As a result, the evaluated behavioural parameters
      were dose-relatedly affected by MPEP. Low-dosed MPEP (10 mg/kg, i.p.) did not
      affect spontaneous locomotion, reduced cocaine-induced hyperlocomotion and
      produced sensitized locomotion, while showing no effect on sensitized locomotion
      induced by repeated cocaine or morphine. Low-dosed MPEP did not genuinely block
      development of cocaine- and morphine-CPP, but rendered CPP expression state
      dependent. The medium MPEP-dose (30 mg/kg) was most effective in reducing
      spontaneous locomotion. The high MPEP-dose (50 mg/kg) was most effective in
      reducing both body-weight and morphine-CPP expression. Cocaine-CPP expression was
      not affected by any MPEP-dose. In conclusion, mGluR5 are involved in modulation
      of spontaneous and cocaine-induced locomotion, in state-dependent learning and in
      expression of morphine-CPP. Thus, MPEP may be beneficial for relapse prevention
      in morphine-addicts.

PMID- 15555633
TI  - Pentobarbital induces thalamic oscillations in brain slices, modulated by GABA
      and glycine receptors.
AB  - We studied the effects of pentobarbital and antagonists of glutamate, gamma
      aminobutyrate (GABA), and glycine receptors on extracellular activity in
      ventrobasal thalamic slices. Pentobarbital at sedative-hypnotic concentration (20
      microM) reversibly induced 1-15 Hz oscillations. Sustained oscillations required
      electrical stimulation of internal capsule, but not elevated temperature or low
      [Mg2+]. Anesthetic concentration (200 microM) of pentobarbital evoked only
      transient oscillations. Kynurenate-sensitive glutamate receptors were essential
      for oscillations. GABA(A) antagonism (bicuculline, 50 microM or gabazine, 20
      microM) suppressed oscillations at 5-15 Hz. GABA(B) antagonism (CGP 35348, 100
      nM), or antagonism of glycine receptors (strychnine, 1 microM) suppressed
      oscillations at 1-4 and 11-15 Hz. GABA and glycine receptors modulated
      oscillation frequency. For elimination, oscillations required GABA antagonists
      and strychnine. Receptors for glutamate and glycine mediated oscillations during
      GABA receptor blockade in ventrobasal nuclei, or on disconnection from nRT.
      Glycine receptors were critical for oscillations in dorsal thalamic network,
      divested of GABAergic inhibition. Glutamate and GABA receptors mediated
      pentobarbital-induced oscillations in nRT, disconnected from ventrobasal nuclei.
      Hence, pentobarbital oscillogenesis occurred in isolated networks of the
      ventrobasal and reticularis nuclei mediated by glutamate receptors, with
      frequency modulation by GABA(A), GABA(B), and glycine receptors. These stationary
      oscillations represent a model of sedation-hypnosis, amenable to pharmacological
      analysis.

PMID- 15555634
TI  - Molecular determinants of ligand discrimination in the glutamate-binding pocket
      of the NMDA receptor.
AB  - Binding of glutamate to ionotropic glutamate receptors occurs within a bilobate
      binding pocket built from conserved S1 and S2 domains. Using the crystal
      structure of the binding region of the (RS)-2-amino-3-(3-hydroxy-5-methyl-4
      isoxazolyl)-propionic acid (AMPA)-selective GluR2 subunit, we identified
      determinants of ligand selectivity and efficacy within the glutamate-binding
      pocket of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor by site
      directed mutagenesis. Electrophysiological analyses of mutated NR2B polypeptides
      revealed drastic effects on the affinity of L-glutamate but not of the co-agonist
      glycine. With seven out of 19 substitutions, we found differences in the potency
      of the full agonist L-glutamate and the partial agonist NMDA. In particular,
      substitutions located at the interface between the S1 and S2 domains resulted in
      changes of agonist efficacy, suggesting a role in transducing the ligand-binding
      signal. Inhibition by the competitive antagonist D-AP5 was highly sensitive to
      replacement of residues involved in stabilization of the closed conformation of
      the binding pocket, consistent with antagonists preventing closure of the binding
      pocket. In addition, we identified residues predicted to be important for
      liganding the methyl group of NMDA. Collectively our data describe specific side
      chain interactions that determine ligand efficacy and pharmacology at the
      glutamate site of the NMDA receptor.

PMID- 15555635
TI  - Effects of distinct classes of N-methyl-D-aspartate receptor antagonists on
      seizures, axonal sprouting and neuronal loss in vitro: suppression by NR2B
      selective antagonists.
AB  - Chronic treatment with high-affinity, competitive N-methyl-D-aspartate receptor
      (NMDAR) antagonists can promote axonal sprouting, induce neuronal loss and
      exacerbate seizures associated with temporal lobe epilepsy. Whether moderate
      affinity uncompetitive and NR2B subunit-selective NMDAR antagonists elicit
      similar responses remains largely unexplored. We directly compared the effects of
      distinct classes of NMDAR antagonists on electrographic seizures, axonal
      sprouting and neuronal survival using electrophysiological recordings and
      histology in hippocampal slice cultures treated chronically with vehicle, D-APV
      (high-affinity competitive), Ro 25-6981 or ifenprodil (NR2B-selective), or
      memantine (moderate-affinity uncompetitive). Granule cell layer field potential
      recordings revealed multiple spontaneous electrographic seizures in vehicle
      treated cultures following GABA(A) receptor blockade. Compared to vehicle,
      seizures were dramatically reduced in cultures treated with NR2B selective
      antagonists and slightly increased in cultures treated with moderate-affinity
      uncompetitive or high-affinity competitive antagonists. In general, compared to
      vehicle, cultures treated with NR2B selective antagonists exhibited less
      sprouting of granule cell mossy fiber axons (MFS) and more granule cell layer
      neurons. Cultures treated with high-affinity competitive or moderate-affinity
      uncompetitive NMDAR antagonists showed increased MFS and fewer granule cell layer
      neurons. These data reveal differential effects of distinct classes of NMDAR
      antagonists on seizure expression, axonal sprouting and neuronal survival and
      suggest an association between these responses.

PMID- 15555636
TI  - Modulation of memory processes and cellular excitability in the dentate gyrus of
      freely moving rats by a 5-HT4 receptors partial agonist, and an antagonist.
AB  - Firstly, olfactory association learning was used to determine the modulating
      effect of 5-HT4 receptor involvement in learning and long-term memory. Secondly,
      the effects of systemic injections of a 5-HT4 partial agonist and an antagonist
      on long-term potentiation (LTP) and depotentiation in the dentate gyrus (DG) were
      tested in freely moving rats. The modulating role of the 5-HT4 receptors was
      studied by using a potent, 5-HT4 partial agonist RS 67333 [1-(4-amino-5-chloro-2
      methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone] and a selective 5-HT4
      receptor antagonist RS 67532 [1-(4-amino-5-chloro-2-(3,5
      dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-propanone]. Agonist or antagonist
      systemic chronic injections prior to five training sessions yielded a
      facilitatory effect on procedural memory during the first session only with the
      antagonist. Systemic injection of the antagonist only before the first training
      session improved procedural memory during the first session and associative
      memory during the second session. Similar injection with the 5-HT4 partial
      agonist had an opposite effect. The systemic injection of the 5-HT4 partial
      agonist prior to the induction of LTP in the dentate gyrus by high-frequency
      stimulation was followed by a population spike increase, while the systemic
      injection of the antagonist accelerated the depotentiation 48 h later. The
      behavioural and physiological results pointed out the involvement of 5-HT4
      receptors in processing related to the long-term hippocampal-dependent memory
      system, and suggest that specific 5-HT4 agonists could be used to treat amnesic
      patients with a dysfunction in this particular system.

PMID- 15555637
TI  - Nicotine in alcohol deprivation increases alcohol operant self-administration
      during reinstatement.
AB  - Tobacco and alcohol are highly co-abused by humans. Most experimental studies
      have evaluated ethanol consumption in animals exposed concomitantly to nicotine.
      However, little is known regarding the effects of nicotine administered during
      periods of alcohol deprivation. In the present study, adult male Wistar rats with
      an extended background of operant self-administration of ethanol were alcohol
      deprived and treated with nicotine (0.1, 0.2, 0.4 and 0.8 mg/kg) or saline during
      five consecutive days in one chamber of a place conditioning apparatus. Nicotine
      induced changes in locomotion were monitored daily, whereas the expression of
      place conditioning was studied the day after the last nicotine injection. Forty
      eight hours after testing for conditioning, the animals resumed operant self
      administration of ethanol and their alcohol intake was evaluated during the next
      14 days. We observed that alcohol consumption was increased in animals treated
      with nicotine at doses of 0.2, 0.4 and 0.8 mg/kg but not in animals treated with
      the dose of 0.1 mg/kg or saline. Additionally, the dose of 0.8 mg/kg of nicotine
      not only induced persistent changes in alcohol self-administration but also
      produced conditioned place aversion and depressed locomotor activity. These
      results indicate that nicotine administration during the ethanol deprivation
      period can exacerbate the maintenance of alcohol consumption.

PMID- 15555639
TI  - Anticonvulsant action of GBR-12909 and citalopram against acute experimentally
      induced limbic seizures.
AB  - We recently showed that intrahippocampally administered dopamine and serotonin
      exert concentration-dependent non-protective, protective and proconvulsant
      effects against limbic seizures in rats. Anticonvulsant action was mediated via,
      respectively, hippocampal D2 and 5-HT1A receptor stimulation, while proconvulsant
      effects were associated with concomitant hippocampal glutamate increases. We here
      examined whether increases in endogenous hippocampal dopamine and serotonin exert
      similar actions. Initially, dose-response experiments were performed with
      intrahippocampal perfusions of GBR-12909 and citalopram, respectively, selective
      dopamine and serotonin re-uptake blockers. Based on their effects on
      monoaminergic release, a potential non-protective, protective and proconvulsant
      concentration was selected. The predicted non-protective GBR-12909 (10 microM)
      and citalopram (0.5 microM) concentrations failed to prevent pilocarpine-induced
      seizures. The predicted protective GBR-12909 (100 microM) and citalopram (1
      microM) perfusions resulted in complete anticonvulsant action, again mediated by
      D2 and 5-HT1A receptors. Unexpectedly, at predicted proconvulsant concentrations
      complete anticonvulsant action was obtained and hippocampal Glu remained
      unaltered. This study shows that selective monoamine re-uptake blockers have
      important anticonvulsant properties. Based on the previously established
      anticonvulsant monoamine ranges, anticonvulsant threshold concentrations can be
      predicted for compounds with endogenous dopamine or serotonin promoting effects.
      Non-selective actions curtailing glutamatergic activity may further be
      responsible for the unexpected anticonvulsant effects at predicted proconvulsant
      concentrations.

PMID- 15555638
TI  - Enantio-selective inhibition of (1R,9S)- and (1S,9R)-beta-hydrastines on dopamine
      biosynthesis in PC12 cells.
AB  - The inhibitory effects of (1R,9S)- and (1S,9R)-enantiomers of beta-hydrastine
      (BHS) on dopamine biosynthesis in PC12 cells were investigated. (1R,9S)-BHS
      decreased the intracellular dopamine content with the IC50 value of 14.3 microM
      at 24 h, but (1S,9R)-BHS did not. (1R,9S)-BHS was not cytotoxic at concentrations
      up to 250 microM towards PC12 cells. In these conditions, (1R,9S)-BHS inhibited
      tyrosine hydroxylase (TH) activity mainly in a concentration-dependent manner
      (33% inhibition at 20 microM) and decreased TH mRNA level in PC12 cells. The
      inhibitory patterns of dopamine content and TH activity by (1R,9S)-BHS showed
      similar behavioral curves. (1R,9S)-BHS at 10-50 microM also reduced the
      intracellular cyclic AMP level and Ca2+ concentration. In addition, treatment of
      L-DOPA at 20-50 microM for 24 h increased the intracellular dopamine content to
      198-251% compared with the control in PC12 cells. However, the increase in
      dopamine levels induced by L-DOPA (20-50 microM) was reduced when L-DOPA was
      combined with (1R,9S)-BHS (10-50 microM). These results indicate that (1R,9S)
      BHS, but not (1S,9R)-BHS, reduced dopamine content and L-DOPA-induced increase in
      dopamine content, in part, through the inhibition of TH activity and TH gene
      expression in PC12 cells: thus, (1R,9S)-BHS proved to have a function to regulate
      dopamine biosynthesis.

PMID- 15555640
TI  - Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKalpha and
      CaMKKbeta mRNA levels in the hippocampus of transgenic mice expressing antisense
      RNA against the glucocorticoid receptor.
AB  - Antidepressants up-regulate the cAMP response element binding protein (CREB) and
      the brain-derived neurotrophic factor (BDNF) in hippocampus and these effects
      contribute to the protection of hippocampal neurons from stressful stimuli such
      as high glucocorticoid levels. CREB can be activated by both protein kinase A and
      by Ca2+-calmodulin-dependent protein kinases (CaMKs), which are in turn
      phosphorylated by their upstream activators CaMKKalpha and CaMMKKbeta. Using in
      situ hybridization, we examined the effects of chronic treatment with fluoxetine
      (FLU) or desipramine (DMI) on BDNF, CaMKKalpha and CaMKKbeta mRNAs in the
      hippocampus of wild-type (Wt) and transgenic (TG) mice characterized by
      glucocorticoid receptor (GR) dysfunction. Basal levels of CaMKKbeta were down
      regulated in the CA3 region of TG mice. DMI decreased the expression of both
      CaMKKalpha and CaMMKKbeta in the CA3 region of Wt mice. FLU up-regulated BDNF
      mRNA levels in the CA3 of TG animals while both FLU and DMI increased BDNF gene
      expression in the dentate gyrus (DG) of TG animals. Our results demonstrate a
      different regulation of BDNF expression by antidepressant drugs in the
      hippocampus of Wt and TG animals. Moreover, for the first time, a role for CaMKKs
      in the mechanism of action of antidepressant agents, at least in the hippocampus,
      is reported. These data are discussed in view of interactions existing between
      CaMK pathway and GR-mediated gene transcription.

PMID- 15555641
TI  - Effects of the cocaine- and amphetamine-regulated transcript peptide on the
      turnover of dopamine in tuberoinfundibular neurons and serum prolactin levels:
      studies using estrogen, melanin concentrating hormone, and melanocortin.
AB  - Effects of the cocaine- and amphetamine-regulated transcript (CART) peptide on
      tuberoinfundibular dopaminergic (TIDA) neurons were examined in female and male
      Sprague-Dawley rats in the morning and afternoon. We also examined the blocking
      effects of melanin concentrating hormone (MCH) and the antagonists of alpha
      melanocyte stimulating hormone (alpha-MSH), SHU9119 and HS014, on stimulation
      induced by the CART peptide in TIDA systems. Intracerebroventricular
      administration of 1 mug CART peptide (55-102) at 45 min, either in the morning or
      afternoon, produced an increase in the median eminence (ME) DOPAC (3,4
      dihydroxyphenylacetic acid) level and a corresponding decrease in serum prolactin
      (PRL) levels. This resulted from stimulation of TIDA neurons regardless of
      castration, and whether or not male and female rats were estrogen-primed. The
      stimulatory effects of the CART peptide on ME DOPAC levels were similar in the
      morning and afternoon in both male and female rats. Central treatment with 1
      microg SHU9119, HS014, or MCH significantly decreased the ME DOPAC levels and
      elevated serum PRL levels in female rats. However, only MCH prevented the
      stimulatory effect of the CART peptide on TIDA neurons. These results indicate
      that stimulation by the CART peptide on TIDA neurons is gender-independent; and
      this stimulatory effect can be blocked by MCH, but not the antagonists of alpha
      MSH.

PMID- 15555642
TI  - Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity
      and memory performance.
AB  - An essential element of the signalling cascade leading to synaptic plasticity is
      the intracellular second messenger molecule guanosine 3',5'-cyclic monophosphate
      (cGMP). Using the novel, potent, and selective inhibitor Bay 60-7550, we show
      that the enzyme 3',5'-cyclic nucleotide phosphodiesterase type 2 (PDE2) is
      responsible for the degradation of newly synthesized cGMP in cultured neurons and
      hippocampal slices. Inhibition of PDE2 enhanced long-term potentiation of
      synaptic transmission without altering basal synaptic transmission. Inhibition of
      PDE2 also improved the performance of rats in social and object recognition
      memory tasks, and reversed MK801-induced deficits in spontaneous alternation in
      mice in a T-maze. Our data provide strong evidence that inhibition of PDE2 can
      improve memory functions by enhancing neuronal plasticity.

PMID- 15555643
TI  - Activation of ureter nociceptors by exogenous and endogenous ATP in guinea pig.
AB  - This study was conducted to determine whether adenosine 5'-triphosphate (ATP)
      contributes to nociceptor activity induced by ureter distension. Multifibre
      recordings of ureter afferents were made using the guinea pig ureter preparation
      perfused in vitro. Distension of the ureter resulted in an initial rapid and
      later maintained increase in afferent nerve discharge. Intraluminal application
      of ATP (10-1000 microM, 0.1 ml/min for 3 min) or alpha,beta-meATP (10-1000
      microM) mimicked these increases in afferent activity. The afferent responses
      consisted of fast and slow components. Both agonists caused a sensitisation of
      the afferents to ureter distensions. TNP-ATP (30 microm), a P2X3 receptor
      antagonist, and the non-specific P2 antagonist, PPADS (100 microm), blocked the
      rapid and reduced the slower response to ATP. The remaining responses were
      blocked by the selective A1 receptor antagonist, DPCPX. TNP-ATP and PPADS reduced
      distension-induced afferent activity. The selective ecto-ATPase inhibitor, ARL
      67156 (100, 200 microM) and suramin (100, 200 microM), an ecto-nucleotidase
      inhibitor as well as a P2 receptor antagonist, produced an increase in baseline
      and distension-induced discharge. These results indicate that the ureter
      epithelium may tonically (at rest) as well as phasically (on distension) release
      ATP, which stimulates afferent terminals by interacting with multiple P2 and P1
      receptors.

PMID- 15555644
TI  - Modulation of voltage-dependent sodium channels by the delta-agonist SNC80 in
      acutely isolated rat hippocampal neurons.
AB  - Following activation, voltage-gated Na+ currents (I(Na)) inactivate on two
      different time scales: fast inactivation takes place on a time scale of
      milliseconds, while slow inactivation takes place on a time scale of seconds to
      minutes. Both fast and slow inactivation processes govern availability of Na+
      channels. In this study, the effects of the delta-opioid receptor agonist SNC80
      on slow and fast inactivation of I(Na) in rat hippocampal granule cells were
      analyzed in detail. Following application of SNC80, a block of the peak Na+
      current amplitude (EC50: 50.6 microM, Hill coefficient: 0.518) was observed.
      Intriguingly, SNC80 (50 microM) also caused a selective effect on slow but not
      fast inactivation processes, with a notable increase in the fraction of Na+
      channels undergoing slow inactivation during prolonged depolarization. In
      addition, recovery from slow inactivation was considerably slowed. At the same
      time, fast recovery processes were unaffected. The effects of SNC80 were not
      mimicked by the peptide delta-receptor agonist DPDPE (10 microM), and were not
      inhibited by the opioid receptor antagonists naloxone (50-300 microM) or
      naltrindole (10 and 100 microM), indicating an opioid receptor independent
      modulation of Na+ channels. These data suggest that SNC80 not only affects delta
      opioid receptors, but also voltage-gated Na+ channels. SNC80 is to our knowledge
      hitherto the only substance that selectively influences slow but not fast
      inactivation processes and could provide an important tool in unraveling the
      mechanism underlying these distinct biophysical processes.

PMID- 15555645
TI  - US health care: a state lottery?

PMID- 15555646
TI  - The important world of drug prequalification.

PMID- 15555647
TI  - Military and public-health sciences need to ally.

PMID- 15555648
TI  - The war in Iraq: civilian casualties, political responsibilities.

PMID- 15555649
TI  - Mortality before and after the invasion of Iraq in 2003.

PMID- 15555650
TI  - Implications of defibrillation.

PMID- 15555651
TI  - Predicting individual outcomes in hepatocellular carcinoma.

PMID- 15555652
TI  - Potential neurovirulence of common cold virus.

PMID- 15555653
TI  - Strokes and holes and headaches: are they a package deal?

PMID- 15555655
TI  - Military medicine and human rights.

PMID- 15555656
TI  - Military medicine and human rights.

PMID- 15555657
TI  - World Bank pseudoscience?

PMID- 15555659
TI  - Statins and rheumatoid arthritis.

PMID- 15555660
TI  - Statins and rheumatoid arthritis.

PMID- 15555661
TI  - Statins and rheumatoid arthritis.

PMID- 15555663
TI  - Circulation.

PMID- 15555664
TI  - Route of corruption in Poland's health-care system.

PMID- 15555665
TI  - Mortality before and after the 2003 invasion of Iraq: cluster sample survey.
AB  - BACKGROUND: In March, 2003, military forces, mainly from the USA and the UK,
      invaded Iraq. We did a survey to compare mortality during the period of 14.6
      months before the invasion with the 17.8 months after it. METHODS: A cluster
      sample survey was undertaken throughout Iraq during September, 2004. 33 clusters
      of 30 households each were interviewed about household composition, births, and
      deaths since January, 2002. In those households reporting deaths, the date,
      cause, and circumstances of violent deaths were recorded. We assessed the
      relative risk of death associated with the 2003 invasion and occupation by
      comparing mortality in the 17.8 months after the invasion with the 14.6-month
      period preceding it. FINDINGS: The risk of death was estimated to be 2.5-fold
      (95% CI 1.6-4.2) higher after the invasion when compared with the preinvasion
      period. Two-thirds of all violent deaths were reported in one cluster in the city
      of Falluja. If we exclude the Falluja data, the risk of death is 1.5-fold (1.1
      2.3) higher after the invasion. We estimate that 98000 more deaths than expected
      (8000-194000) happened after the invasion outside of Falluja and far more if the
      outlier Falluja cluster is included. The major causes of death before the
      invasion were myocardial infarction, cerebrovascular accidents, and other chronic
      disorders whereas after the invasion violence was the primary cause of death.
      Violent deaths were widespread, reported in 15 of 33 clusters, and were mainly
      attributed to coalition forces. Most individuals reportedly killed by coalition
      forces were women and children. The risk of death from violence in the period
      after the invasion was 58 times higher (95% CI 8.1-419) than in the period before
      the war. INTERPRETATION: Making conservative assumptions, we think that about
      100000 excess deaths, or more have happened since the 2003 invasion of Iraq.
      Violence accounted for most of the excess deaths and air strikes from coalition
      forces accounted for most violent deaths. We have shown that collection of public
      health information is possible even during periods of extreme violence. Our
      results need further verification and should lead to changes to reduce non
      combatant deaths from air strikes.

PMID- 15555666
TI  - Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected
      Zambian children (CHAP): a double-blind randomised placebo-controlled trial.
AB  - BACKGROUND: No trials of co-trimoxazole (trimethoprim-sulfamethoxazole)
      prophylaxis for HIV-infected adults or children have been done in areas with high
      levels of bacterial resistance to this antibiotic. We aimed to assess the
      efficacy of daily co-trimoxazole in such an area. METHODS: We did a double-blind
      randomised placebo-controlled trial in children aged 1-14 years with clinical
      features of HIV infection in Zambia. Primary outcomes were mortality and adverse
      events possibly related to treatment. Analysis was by intention to treat.
      FINDINGS: In October, 2003, the data and safety monitoring committee recommended
      early stopping of the trial. 541 children had been randomly assigned; seven were
      subsequently identified as HIV negative and excluded. After median follow-up of
      19 months, 74 (28%) children in the co-trimoxazole group and 112 (42%) in the
      placebo group had died (hazard ratio [HR] 0.57 [95% CI 0.43-0.77], p=0.0002).
      This benefit applied in children followed up beyond 12 months (n=320, HR 0.48
      [0.27-0.84], test for heterogeneity p=0.60) and across all ages (test for
      heterogeneity p=0.82) and baseline CD4 counts (test for heterogeneity p=0.36). 16
      (6%) children in the co-trimoxazole group had grade 3 or 4 adverse events
      compared with 18 (7%) in the placebo group. These events included rash (one
      placebo), and a neutrophil count on one occasion less than 0.5x10(9)/L (16 [6%]
      co-trimoxazole vs seven [3%] placebo, p=0.06). Pneumocystis carinii was
      identified by immunofluorescence in only one (placebo) of 73 nasopharyngeal
      aspirates from children with pneumonia. INTERPRETATION: Our results suggest that
      children of all ages with clinical features of HIV infection should receive co
      trimoxazole prophylaxis in resource-poor settings, irrespective of local
      resistance to this drug.

PMID- 15555667
TI  - Isolation and culture of human muscle-derived stem cells able to differentiate
      into myogenic and neurogenic cell lineages.
AB  - BACKGROUND: Skeletal-muscle-derived stem cells seem to be a distinct population
      of immature progenitors of satellite cells, but their functional properties
      remain unclear, especially in human adult tissue. We investigated their
      differentiation in samples of skeletal muscle obtained from adults undergoing
      cardiovascular surgery. METHODS: Samples were obtained from the brachioradialis
      muscle of 12 patients in whom the radial artery was the conduit for myocardial
      revascularisation. The stem cells were isolated by a procedure similar to that
      used for rat gastrocnemius and cultured in medium optimised for growth of neural
      stem cells. Cytometry was used for phenotypic characterisation and
      immunocytochemistry and RT-PCR to assess differentiation. Immunohistochemistry
      was used to examine engraftment of skeletal-muscle-derived stem cells into
      injured rat spinal cord. FINDINGS: The skeletal-muscle stem cells consisted of
      two distinct types: one with the typical spindle morphology of satellite cells,
      the other of rounded cells. Some cultures could be maintained for longer than 6
      months. The cells were mainly positive for desmin and to a lesser extent CD105,
      vimentin, and AC133/CD133, but negative for FLK-1/KDR, CD34, CD31, CD45, von
      Willebrand factor, Ve-cadherins, and BCL2. After in-vitro differentiation, the
      cells were able to organise skeletal-muscle fibres and stained positively for
      striated-muscle actin, smooth-muscle actin, and desmin. Moreover, they
      differentiated into astrocytes and neurons, as confirmed by positive staining for
      characteristic proteins. INTERPRETATION: Adult human skeletal muscle includes a
      population of progenitor stem cells that can generate cells of the same lineage
      and cells with neurogenic properties. Muscle may therefore be a tissue source for
      the isolation of pluripotent stem cells for development of cell-based therapies
      for human myogenic and neurogenic diseases.

PMID- 15555668
TI  - A missing denture.

PMID- 15555669
TI  - Spina bifida.
AB  - Spina bifida results from failure of fusion of the caudal neural tube, and is one
      of the most common malformations of human structure. The causes of this disorder
      are heterogeneous and include chromosome abnormalities, single gene disorders,
      and teratogenic exposures. However, the cause is not known in most cases. Up to
      70% of spina bifida cases can be prevented by maternal, periconceptional folic
      acid supplementation. The mechanism underlying this protective effect is unknown,
      but it is likely to include genes that regulate folate transport and metabolism.
      Individuals with spina bifida need both surgical and medical management. Although
      surgical closure of the malformation is generally done in the neonatal period, a
      randomised clinical trial to assess in utero closure of spina bifida has been
      initiated in the USA. Medical management is a lifelong necessity for individuals
      with spina bifida, and should be provided by a multidisciplinary team.

PMID- 15555670
TI  - Malaria misdiagnosis: effects on the poor and vulnerable.
AB  - CONTEXT: Effective and affordable treatment is recommended for all cases of
      malaria within 24 h of the onset of illness. Most cases of "malaria" (ie, fever)
      are self-diagnosed and most treatments, and deaths, occur at home. The most
      ethical and cost-effective policy is to ensure that newer drug combinations are
      only used for true cases of malaria. Although it is cost effective to improve the
      accuracy of malaria diagnosis, simple, accurate, and inexpensive methods are not
      widely available, particularly in poor communities where they are most needed.
      STARTING POINT: In a recent study in Uganda, Karin Kallander and colleagues
      emphasise the difficulty in making a presumptive diagnosis of malaria, and
      highlight the urgent need for improved diagnostic tools that can be used at
      community and primary-care level, especially in poorer populations (Acta Trop
      2004; 90: 211-14). WHERE NEXT? Health systems need strengthening at referral and
      community level, so that rapid accurate diagnosis and effective treatment is
      available for those who are least able to withstand the consequences of illness.
      Indirect evidence strongly suggests that misdiagnosis of malaria contributes to a
      vicious cycle of increasing ill-health and deepening poverty. Much better direct
      evidence is needed about why and how misdiagnosis affects the poor and
      vulnerable.

PMID- 15555671
TI  - Public nutrition in complex emergencies.
AB  - Public nutrition is a broad-based, problem-solving approach to addressing
      malnutrition in complex emergencies that combines analysis of nutritional risk
      and vulnerability with action-oriented strategies, including policies,
      programmes, and capacity development. This paper focuses on six broad areas:
      nutritional assessment, distribution of a general food ration, prevention and
      treatment of moderate malnutrition, treatment of severe malnutrition in children
      and adults, prevention and treatment of micronutrient deficiency diseases, and
      nutritional support for at-risk groups, including infants, pregnant and lactating
      women, elderly people, and people living with HIV. Learning and documenting good
      practice from previous emergencies, the promotion of good practice in current
      emergencies, and adherence to international standards and guidelines have
      contributed to establishing the field of public nutrition. However, many
      practical challenges reduce the effectiveness of nutritional interventions in
      complex emergencies, and important research and programmatic questions remain.

PMID- 15555672
TI  - Diffuse bone pain in a young woman.

PMID- 15555674
TI  - Animal cognition: defining the issues.
AB  - The assessment of cognitive functions in rodents represents a critical
      experimental variable in many research fields, ranging from the basic cognitive
      neurosciences to psychopharmacology and neurotoxicology. The increasing use of
      animal behavioral tests as 'assays' for the assessment of effects on learning and
      memory has resulted in a considerable heterogeneity of data, particularly in the
      field of behavioral and psycho pharmacology. The limited predictive validity of
      changes in behavioral performance observed in standard animal tests of learning
      and memory indicates that a renewed effort to scrutinize the validity of these
      tests is warranted. In humans, levels of processing (effortful vs. automatic) and
      categories of information (procedural vs. episodic/declarative) are important
      variables of cognitive operations. The design of tasks that assess the recall of
      'episodic' or 'declarative' information appears to represent a particular
      challenge for research using laboratory rodents. For example, the hypothesis that
      changes in inspection time for a previously encountered place or object are based
      on the recall of declarative/episodic information requires substantiation. In
      order to generalize findings on the effects of neuronal or pharmacological
      manipulations on learning and memory, obtained from one species and one task, to
      other species and other tasks, the mediating role of important sets of variables
      which influence learning and memory (e.g. attentional, affective) needs to be
      determined. Similar to the view that a neuronal manipulation (e.g. a lesion)
      represents a theory of the condition modeled (e.g. a degenerative disorder), an
      animal behavioral task represents a theory of the behavioral/cognitive process of
      interest. Therefore, the test of hypotheses regarding the validity of procedures
      used to assess cognitive functions in animals is an inherent part of the research
      process.

PMID- 15555675
TI  - Conditioning and cognition.
AB  - Animals' abilities to use internal representations of absent objects to guide
      adaptive behavior and acquire new information, and to represent multiple spatial,
      temporal, and object properties of complex events and event sequences, may
      underlie many aspects of human perception, memory, and symbolic thought. In this
      review, two classes of simple associative learning tasks that address these core
      cognitive capacities are discussed. The first set, including reinforcer
      revaluation and mediated learning procedures, address the power of Pavlovian
      conditioned stimuli to gain access, through learning, to representations of
      upcoming events. The second set of investigations concern the construction of
      complex stimulus representations, as illustrated in studies of contextual
      learning, the conjunction of explicit stimulus elements in configural learning
      procedures, and recent studies of episodic-like memory. The importance of
      identifying both cognitive process and brain system bases of performance in
      animal models is emphasized.

PMID- 15555676
TI  - Memory processes in classical conditioning.
AB  - Classical conditioning provides a rich and powerful method for studying basic
      learning, memory, and emotion processes in animals. However, it is important to
      recognize that an animal's performance in a conditioning experiment provides only
      an indirect indication of what it has learned. Various remembering and forgetting
      processes, in addition to other psychological processes, may intervene and
      complicate what investigators can infer about learning from performance. This
      article reviews the role of context, interference, and retrieval in a number of
      classical conditioning phenomena (e.g. extinction), and provides an overview of
      how long-term and short-term memory processes influence behavior as it is studied
      in classical conditioning.

PMID- 15555677
TI  - Understanding contextual fear conditioning: insights from a two-process model.
AB  - Contextual fear conditioning is an important behavioral paradigm for studying the
      neurobiology of learning and memory and the mnemonic function of the hippocampus.
      We suggest that research in this domain can profit by a better theoretical
      understanding of the processes that contribute to this phenomenon. To facilitate
      this understanding, we describe a theory which assumes that physical elements of
      a conditioning context represented in the brain as either (a) a set of
      independent features or (b) features bound into a conjunctive representation by
      the hippocampus which supports pattern completion. Conditioning produced by
      shocking a rat in a particular context, in principle, can be produced by
      strengthening connections between the feature representations and/or the
      conjunctive representation and basolateral region of the amygdala. We illustrate
      how this theory clarifies some of the complexities associated with the existing
      literature and how it can be used to guide future empirical work. We also argue
      that the mechanisms (conjunctive representations and pattern completion) that
      mediate the contribution the hippocampus makes to contextual fear conditioning
      are the same ones that enable the hippocampus to support declarative memory in
      humans.

PMID- 15555678
TI  - Rodent spatial navigation: at the crossroads of cognition and movement.
AB  - Tasks that measure spatial learning and navigation have become central to
      contemporary research programs concerned with identifying the neurobiological
      bases of learning and memory. Although the past three decades have seen an
      explosion of research reports on rodent navigation, only a small proportion of
      this research has been directly aimed at identifying the constituent
      psychological and behavioral processes involved in navigation. Such efforts are
      critical for establishing a complete neuroscientific explanation of spatial
      behavior and navigation, however, the majority of these research efforts have
      focused on identifying a single behavioral dissociation (e.g. place learning vs
      cued navigation). Experimental comparisons limited to only two possible
      alternatives can lead to erroneous or otherwise incomplete conclusions regarding
      how animals navigate. Because multiple sources of information may come to bear on
      an animal's behavior in spatial tasks, consideration of these sources and their
      interaction may avoid certain pitfalls inherent in the single dissociation
      approach. We offer a descriptive model of rodent navigation which includes three
      important dimensions: reference frame, information, and movement control. A
      variety of extant behavioral and neurophysiological data that support the basic
      utility of this conceptual framework are discussed.

PMID- 15555679
TI  - An overview of the tasks used to test working memory in rodents.
AB  - In rodents, working memory is a representation of an object, stimulus, or spatial
      location that is typically used within a testing session, but not between
      sessions, to guide behaviour. In this review we consider a number of the tasks
      used to assess this type of memory in the rodent, and highlight some of their
      limitations. Although the concept of working memory as applied to rodents has its
      origin in the experiments of David Olton and Werner Honig in the 1970s, many
      earlier experiments assessed the same type of memory under the guise of delayed
      reaction or alternation paradigms. We revisit these early tasks, and also
      consider the nature of working memory used on maze tasks, operant box based
      tasks, and non-spatial delayed non-matching to sample paradigms.

PMID- 15555680
TI  - Some pitfalls in measuring memory in animals.
AB  - Because the presence or absence of memories in the brain cannot be directly
      observed, scientists must rely on indirect measures and use inferential reasoning
      to make statements about the status of memories. In humans, memories are often
      accessed through spoken or written language. In animals, memory is accessed
      through overt behaviours such as running down an arm in a maze, pressing a lever,
      or visiting a food cache site. Because memory is measured by these indirect
      methods, errors in the veracity of statements about memory can occur. In this
      brief paper, we identify three areas that may serve as pitfalls in reasoning
      about memory in animals: (1) the presence of 'silent associations', (2)
      intrusions of species-typical behaviours on memory tasks, and (3) improper
      mapping between human and animals memory tasks. There are undoubtedly other areas
      in which scientists should act cautiously when reasoning about the status of
      memory.

PMID- 15555681
TI  - The challenges of understanding mammalian cognition and memory-based behaviours:
      an interactive learning and memory systems approach.
AB  - Various research problems are presented to illustrate the utility of using the
      interactive multiple learning and memory systems view to better understand normal
      and abnormal manifestations of mammalian behaviour. Evidence for incidental
      learning and memory processes is presented and various implications of this work
      are discussed. Empirical and theoretical work directed at understanding the
      cognitive and non-cognitive processes associated with place learning in the water
      task and context conditioning during aversive events is also presented.

PMID- 15555682
TI  - Systems-level integration of interval timing and reaction time.
AB  - Reaction time (RT) procedures are a prominent tool for the study of information
      processing by humans and other animals. The interpretation of how RT changes
      after manipulating the appropriate experimental variables has contributed to the
      contemporary understanding of a variety of cognitive constructs, including
      attention and memory. With the use of properly designed tasks, evaluating how RT
      is modified in response to various neural perturbations has become common within
      the realms of behavioral and cognitive neuroscience. One interesting observation
      made during both human and animal RT experiments is that the RT to a signal often
      speeds-up as more time is allotted to prepare for the signal's onset-referred to
      as the preparatory interval (PI) effect. In the human RT literature, the PI
      effect has been used as evidence for time estimation playing a fundamental role
      in the determination of RT. On the other hand, our theoretical understanding of
      time estimation remains largely divorced from the RT findings in the animal
      cognition literature. In order to bridge these different perspectives, we provide
      here a review of the behavioral parallels between RT and interval-timing
      experiments. Moreover, both the PI effect and interval timing are shown to be
      jointly influenced by neuropathologies such as Parkinson's disease in humans or
      dopamine-depleting brain lesions in experimental animals. The primary goal of
      this review is to consider human and animal RT experiments within the broader
      context of interval timing. This is accomplished by first integrating human RT
      theory with scalar timing theory-the leading model of interval timing. Following
      this, both RT and interval timing are discussed at a brain systems level insofar
      as these two processes share common neural substrates. Our conclusion is that
      interval timing and RT processes are in fact two sides of the same coin.

PMID- 15555683
TI  - Prefrontal executive and cognitive functions in rodents: neural and neurochemical
      substrates.
AB  - The prefrontal cortex has been implicated in a variety of cognitive and executive
      processes, including working memory, decision-making, inhibitory response
      control, attentional set-shifting and the temporal integration of voluntary
      behaviour. This article reviews current progress in our understanding of the
      rodent prefrontal cortex, especially evidence for functional divergence of the
      anatomically distinct sub-regions of the rat prefrontal cortex. Recent findings
      suggest clear distinctions between the dorsal (precentral and anterior cingulate)
      and ventral (prelimbic, infralimbic and medial orbital) sub-divisions of the
      medial prefrontal cortex, and between the orbitofrontal cortex (ventral orbital,
      ventrolateral orbital, dorsal and ventral agranular cortices) and the adjacent
      medial wall of the prefrontal cortex. The dorso-medial prefrontal cortex is
      implicated in memory for motor responses, including response selection, and the
      temporal processing of information. Ventral regions of the medial prefrontal
      cortex are implicated in interrelated 'supervisory' attentional functions,
      including attention to stimulus features and task contingencies (or action
      outcome rules), attentional set-shifting, and behavioural flexibility. The
      orbitofrontal cortex is implicated in lower-order discriminations, including
      reversal of stimulus-reward associations (reversal learning), and choice
      involving delayed reinforcement. It is anticipated that a greater understanding
      of the prefrontal cortex will come from using tasks that load specific cognitive
      and executive processes, in parallel with discovering new ways of manipulating
      the different sub-regions and neuromodulatory systems of the prefrontal cortex.

PMID- 15555684
TI  - Electroconvulsive therapy in adolescent and adult psychiatric inpatients--a
      retrospective chart design.
AB  - BACKGROUND: The knowledge available on electroconvulsive therapy (ECT) in
      adolescents is largely anecdotal, or based on findings from adults. The aim of
      the present study is to compare the use of ECT in adolescent and adult
      inpatients. METHODS: We retrospectively analyzed the files of all 36 adolescent
      (between the ages of 13 and 19) and 57 randomly selected adult inpatients (above
      the age of 20) treated with ECT in a university-affiliated mental heath center in
      Israel between 1991 and 1997. RESULTS: Sixty one percent of the adolescents
      improved by the end of treatment, and 53% were not hospitalized in the subsequent
      year. The respective percentages among adults were 83% and 49%. Whereas most
      adults were treated with ECT because of schizophrenic disorders, almost half of
      the adolescents received ECT for affective disorders. Significantly more
      adolescents were treated with ECT because of acute life-endangering conditions
      (catatonia or severe suicidal risk). No significant adverse effects were found in
      both groups. LIMITATIONS: Our study is based on a retrospective chart review. The
      adolescent and adult groups are different in psychiatric morbidity, diagnosis and
      outcome, have not been assessed in a blind manner, and we have not used
      standardized psychometric batteries for the evaluation of ECT-related memory
      disturbances. CONCLUSIONS: ECT may be an effective, well-tolerated and safe
      procedure in both adult and adolescent inpatients.

PMID- 15555685
TI  - Expressed emotion as a predictor of outcome among bipolar patients undergoing
      family therapy.
AB  - BACKGROUND: Levels of expressed emotion (EE) in relatives are consistent
      predictors of relapse among bipolar and other mood disordered patients followed
      naturalistically. However, few studies have examined whether levels of EE predict
      the course of illness for patients engaged in psychosocial interventions.
      METHODS: This study examined whether EE levels among caregivers moderated the
      success of family-based psychosocial interventions for patients with bipolar
      disorder. EE was examined as a predictor of symptomatic outcome in two groups:
      (1) bipolar patients receiving family-focused psychoeducational treatment (FFT)
      or integrated family and individual treatment (IFIT), and (2) bipolar patients
      receiving crisis management (CM), a less intensive intervention designed to
      emulate community care. Bipolar patients (N = 125) began the study in an acute
      illness episode, were stabilized on standard pharmacotherapy regimens, and
      followed for up to 2 years. RESULTS: Family EE status was not associated with
      time to relapse in either group. However, patients with high EE relatives
      reported higher levels of depression over the 2-year term of follow-up,
      regardless of treatment condition. An examination of the dimensions of EE
      (critical comments and emotional overinvolvement) indicated that a higher
      frequency of critical comments predicted higher levels of mania and depression at
      follow-up. Additionally, the association between EE criticism and levels of mania
      symptoms was stronger among patients in CM than among patients in family
      treatment. LIMITATIONS: The participants were recruited from two separate
      treatment protocols. Patients in the IFIT protocol were not randomly assigned to
      treatments. CONCLUSIONS: EE is a predictor of symptom severity among bipolar
      patients undergoing pharmacological and psychosocial treatments, but family
      intervention may mitigate this association.

PMID- 15555686
TI  - The role of life events in depression in primary medical care versus psychiatric
      settings.
AB  - BACKGROUND: The relationship between negative life events and depression is
      inconsistent. The purpose of the current study is to investigate the hypothesis
      that depression in the community may be related more to major life events than is
      depression in psychiatric settings. METHODS: This hypothesis was tested using
      depressed primary medical care (PC; n=70) and psychiatric patients (n=62).
      Nondistressed (n=109) and distressed/nondepressed PC patients (n=43) served as
      comparison-control groups. Life events were rated using the contextual method of
      Brown and Harris (Brown, G.W., Harris, T.O., 1978. Social origins of depression.
      Tavistock, London). RESULTS: Depressed PC patients, but not depressed psychiatric
      patients, were significantly more likely to have recent severe events than the
      comparison-control groups. Self-reported distress in the absence of depression
      was not associated with severe life events. LIMITATIONS: History of depression
      was assessed using a simple count of number of previous episodes, and the
      assessment of depression history may require more sophisticated assessment. The
      measure of endogenous depression used in this study was created post-hoc and
      needs replication. CONCLUSIONS: Diathesis-stress models need to accommodate a
      lack of universality for severe stress prior to the onset of depression. Clinical
      strategies may need to reflect patient treatment preferences associated with
      differences across settings with respect to the perceived role of stress in their
      depression.

PMID- 15555687
TI  - Functioning after a major depressive episode: complete or incomplete recovery?
AB  - BACKGROUND: Numerous studies have shown improved functioning after a depression,
      but often substantial limitations at follow-up remained. The goal of this study
      is to examine (1) whether functioning returns to pre-morbid levels after a major
      depressive episode (MDE), (2) predictors of incomplete functional recovery, and
      (3) how these functional levels relate to those in a non-depressed sample.
      METHODS: Data were derived from the Netherlands Mental Health Survey and
      Incidence Study, a prospective general population study with three waves.
      Psychopathology was measured with the Composite International Diagnostic
      Interview (CIDI) and functioning with the Short-Form-36 Health Survey (SF-36).
      One hundred and sixty-five individuals who met criteria for MDE between baseline
      and third wave, but not in the 12 months preceding baseline and third wave were
      selected. RESULTS: Mean post-morbid levels of functioning did not differ from pre
      morbid levels although this level still differed significantly from the non
      depressed sample. Sixty to eighty-five percent of the respondents did better or
      showed no change on different scales after recovery from MDE. Co-morbid substance
      use disorder and anxiety disorder, presence of somatic illness, external mastery,
      low social support and high baseline functioning were predictors of worsened
      functioning. LIMITATIONS: Lay interviewers used fully structured diagnostic
      interviews to determine MDE and functioning was measured using self-report.
      CONCLUSIONS: In general, people who recover from a MDE will also recover from
      functional impairments. The most important predictors of incomplete functional
      recovery are clinical and social in nature whereas personality and demographic
      characteristics are less important.

PMID- 15555688
TI  - The impact of unrecognized bipolar disorders for patients treated for depression
      with antidepressants in the fee-for-services California Medicaid (Medi-Cal)
      program.
AB  - BACKGROUND: This study compares hospital use, suicide risk and health care costs
      of antidepressant patients with recognized bipolar disorders (recognized-BP) and
      unrecognized bipolar disorders (unrecognized-BP) with non-bipolar (non-BP)
      patients. METHODS: Data from the California Medicaid (Medi-Cal) program were used
      to identify 25,460 adults with a new episode of antidepressant therapy.
      Recognized-BP patients received either a bipolar (BP) diagnosis or a mood
      stabilizer (MS) on or before the initiation of antidepressant therapy.
      Unrecognized-BP patients received a BP diagnosis or MS therapy after
      antidepressant initiation. Non-BP patients had no BP diagnosis and no MS use.
      Multivariate models were used to estimate marginal risks and costs across groups.
      RESULTS: Recognized-BP and unrecognized-BP represented 14.9% and 6.2% of all
      antidepressant users, respectively. Less than half of recognized-BP patients used
      a MS medication in conjunction with their antidepressant. Unrecognized-BP
      patients were nearly four times more likely to attempt suicide and 50% more
      likely to be hospitalized than non-BP patients. Recognized-BP patients were at
      lower risk for attempted suicide and hospitalization relative to unrecognized-BP
      patients. Unrecognized-BP patients experienced higher 1-year total costs relative
      to non-BP patients (USD 995, p<0.01) and recognized-BP patients (USD 682,
      p<0.05). LIMITATIONS: Clinically relevant medical records data were not available
      making the classification of patients as unrecognized-BP, recognized-BP and non
      BP imprecise. CONCLUSIONS: Unrecognized-BP is both common and costly. More than
      half of all recognized-BP patients do not use an MS at the time they initiated
      antidepressant therapy. More effort is needed to provide early and correct
      diagnosis and effectively treat both recognized-BP and unrecognized-BP patients.

PMID- 15555689
TI  - Children of a cohort of depressed patients 25 years later: psychopathology and
      relationships.
AB  - BACKGROUND: While many studies have examined cross-sectional or short-term
      effects of parental depression on children, few have studied such children many
      years later when they reach adulthood. It was hypothesised that children of
      patients hospitalised for depression 25 years ago would have more psychological
      morbidity and relationship difficulties than children of a surgical comparison
      group. METHOD: Children (n=94) of depressed patients and a surgical control group
      (n=31) admitted to a teaching hospital 25 years ago were compared on measures of
      psychiatric morbidity, personality, marital and family relationships. RESULTS:
      Compared with control children, children of depressed patients demonstrated
      trends for higher rates of non-phobic anxiety and substance disorders, but
      neither psychological morbidity overall nor affective disorder specifically.
      Compared with control children, children of depressed patients rated their
      relationships with fathers who were spouses of female patients more negatively.
      Having consciously tried to make their own intimate relationships different from
      that of their parents, children of depressed patients and their partners reported
      significantly more caring in their relationships compared with control children
      and their partners. CONCLUSION: In this study of the effects of parental
      depression on children 25 years on, adult children of depressed patients
      demonstrated significant resilience as evidenced by similar rates of overall
      psychiatric morbidity and quality of intimate relationships to controls. They may
      be at risk for specific disorders such as anxiety and substance disorder and have
      problematic relationships with the "well" spouses of depressed patients
      particularly if the "well" spouse is their father.

PMID- 15555690
TI  - Momentary changes in the cardiovascular autonomic system during mental loading in
      patients with panic disorder: a new physiological index "rho(max)".
AB  - BACKGROUND: Although panic disorder (PD) is suggestive of autonomic nervous
      system dysfunction, especially in the cardiovascular autonomic system (CAS), the
      results in many previous studies are still controversial. Using a new
      physiological index which could well reflect emotional reaction to visual stimuli
      (Yoshizawa, M., Sugita, N., Tanaka, A., Abe, K., Yambe, T., Nitta, S., 2001.
      Quantiatative Physioligical Evaluation of Three Dimensional Images. The Seventh
      International Conference on Virtual Systems and Multumedia, 25-27.), we studied
      momentary changes in the CAS in patients with PD during audiovisual stimulation
      (AS) as mental loading. METHODS: During AS, exposed to a video of imaginary
      experiences such as driving a motor vehicle or diving into the sea, blood
      pressure (BP) and heart rate (HR) were measured in 12 remitted patients with PD
      and 19 age- and sex-matched normal controls (NC). We used the maximum cross
      correlation coefficient (rho(max)) from the BP to the HR, whose frequency
      components were limited to around 0.1 Hz. RESULTS: The rho(max) was an available
      index which could detect the momentary changes in the CAS during AS in both
      groups. The two-way ANOVA disclosed significant group and time effects on the
      rho(max). The momentary response to emotional stimuli in the PD patients was
      slower than that in the NC subjects. LIMITATIONS: Antidepressants have a
      potential impact on the autonomic variables in this study. CONCLUSIONS: These
      findings suggest that there may be a dysfunction of the CAS in remitted PD
      patients and that the dysfunction may be one of the trait markers of PD. To
      confirm these findings, however, further studies with a large sample size are
      required.

PMID- 15555691
TI  - Deficiency of theory of mind in patients with remitted mood disorder.
AB  - BACKGROUND: Recent researches on theory of mind (ToM) in patients with mood
      disorders have revealed deficits of ToM ability during episodes. In this study,
      we aimed to test ToM ability among patients with unipolar or bipolar depression
      currently in remission. METHODS: ToM ability and IQ obtained by Wechsler Adult
      Intelligence Scale-Revised (WAIS-R) were evaluated in 50 patients with remitted
      depression, who met the criteria of mood disorders of DSM-IV, and 50 matched
      healthy controls. RESULTS: The patients with mood disorders showed statistically
      significant impairment in a second-order false question (Fisher's Exact Test p <
      0.0001). No significant difference was shown in the other three areas of ToM
      between the patients and the controls. In addition, no correlation of the four
      areas of ToM with IQ obtained by WAIS-R was found. LIMITATIONS: The relation of
      ToM deficit to other specific cognitive impairment was not examined. CONCLUSIONS:
      Our results suggest that depressive patients in symptomatic remission have a
      lower ability of second-order false belief. The ToM impairment suggests a decline
      of skillful social relationships. Evaluation of ToM ability in depressive
      patients in remission may be useful to provide treatment for better social
      adjustment.

PMID- 15555692
TI  - Regional brain responses to serotonin in major depressive disorder.
AB  - BACKGROUND: Positron Emission Tomography (PET) studies have reported altered
      resting regional brain glucose metabolism in mood disorders. This study examines
      the relationship of such changes to serotonin system abnormalities associated
      with depression. METHODS: Thirteen male medication free subjects who were
      inpatients with a DSM-IIIR major depressive disorder and seven healthy male
      subjects underwent an [18F]-fluorodeoxyglucose (18FDG) PET scan on consecutive
      days. Three hours prior to 18FDG subjects received single blind placebo or
      fenfluramine. Comparisons of voxel level regional glucose metabolic rate
      responses (rCMRglu) between groups in the two states were performed with SPM99.
      RESULTS: Unlike healthy male subjects who have significant increases in rCMRglu
      in prefrontal and parietal cortical regions after receiving fenfluramine,
      depressed male subjects have no significant increases in rCMRglu. CONCLUSIONS:
      Blunted increases in rCMRglu in response to fenfluramine in prefrontal and
      parietal cortex are consistent with our previous pilot study and the indoleamine
      hypothesis of depression. Differences in specific brain regions affected between
      this study and previous studies may be attributable to gender differences.

PMID- 15555693
TI  - Using the CES-D in a two-phase survey for depressive disorders among nonreferred
      adolescents in Taipei: a stratum-specific likelihood ratio analysis.
AB  - BACKGROUND: Efficient screening is important in two-phase surveys. We examined
      whether the Center for Epidemiologic Studies Depression Scale (CES-D) is an
      appropriate instrument for screening depressive disorders among adolescents in
      Taipei, an ethnic group whose depression is little known of. METHODS: Among the
      2440 students of a school in Taipei, aged 12 to 16 years who completed the CES-D
      and eating attitude test (EAT; response rate=98.5%), 178 were randomly selected
      from four subgroups defined by the 90th percentile of the two screening tools for
      face-to-face interview, using the Schedule for Affective Disorders and
      Schizophrenia for Children (K-SADS). Discriminatory validities of instruments for
      depressive disorders were estimated, and then a stratum-specific likelihood ratio
      (SSLR) analysis was conducted for instruments with sufficient validity. RESULTS:
      The prevalence estimates of depressive disorders varied with different levels of
      impairment, with a value of 2.4% for major depressive disorder and 0.3% for
      dysthymic disorder if at least two impairment items were endorsed. The areas
      under the receiver operative characteristic (ROC) curves were consistently high
      (0.88-0.90) for major depressive disorder with or without impairment requirement,
      but low (0.49) for dysthymic disorder without impairment requirement. Three
      strata of CES-D scores (0-28, 29-48, and > or =49) were derived for major
      depressive disorder with (SSLR=0.63, 3.00, and 11.75) and without (SSLR=0.61,
      5.09, and 10.42) impairment requirement. CONCLUSIONS: The CES-D is useful in
      screening for major depressive disorder among nonreferred adolescents. Three
      strata are recommended for its practical application.

PMID- 15555694
TI  - Does adjunctive family therapy enhance recovery from bipolar I mood episodes?
AB  - BACKGROUND: Family therapy is sometimes used as adjunctive treatment to
      pharmacotherapy to help patients recover from mood episodes of bipolar I
      disorder. However, the efficacy of this practice is not known. METHODS: Ninety
      two patients meeting criteria for a current bipolar I mood episode were randomly
      assigned to family therapy plus pharmacotherapy, multifamily psychoeducational
      group therapy plus pharmacotherapy, or pharmacotherapy alone. Time to recovery
      was analyzed with survival analysis. RESULTS: The proportion of subjects within
      each treatment group who recovered did not significantly differ, nor did time to
      recovery. LIMITATIONS: The analyses did not include other outcomes such as
      psychosocial functioning, prophylaxis against recurrences of mood episodes, or
      compliance with pharmacotherapy. CONCLUSIONS: Neither adjunctive family therapy
      nor adjunctive multifamily psychoeducational group therapy significantly improves
      the rate of recovery from mood episodes of bipolar I disorder, compared to
      treatment with pharmacotherapy alone.

PMID- 15555695
TI  - Suicide attempts: differences between unipolar and bipolar patients and among
      groups with different lethality risk.
AB  - BACKGROUND: The present naturalistic study aimed to distinguish between suicide
      attempts (SAs) of bipolar and unipolar patients, and among SAs characterized by
      different lethality risk. METHODS: The records of 2395 consecutive admissions to
      our psychiatric intensive care unit (PICU) were assessed for presence of suicide
      attempt (SA). Cases of SA were rated for symptom severity with the brief
      psychiatric rating scale (BPRS), the scale for the assessment of positive
      symptoms (SAPS), the scale for the assessment of negative symptoms (SANS), the
      mini mental state examination (MMSE), the global assessment of functioning scale
      (GAF) and the clinical global impression (CGI). An original questionnaire was
      administered to explore clinical aspects related with suicidal behavior. RESULTS:
      Among 2395 admissions, 80 (3.3%) had attempted suicide. Fifty-three cases (66.2%)
      suffered from a mood episode, including 22 (27.5%) with unipolar depression and
      31 (38.7%) with bipolar depression (types I and II combined) or mixed state,
      while 27 (33.8%) cases received other diagnoses. Forty-eight (60%) cases had
      attempted suicide prior to the index episode. Ten cases (12.5%) had a relative
      who attempted or committed suicide. Thirty-nine cases (48.7%) described their SA
      as impulsive. Twenty cases (25.0%) reported alcohol ingestion before SA. In
      comparison with women, men used more violent methods. Cases characterized by a
      non-lethal risk SA had higher BPRS psychotic cluster and SAPS scores than cases
      with either low or high lethal risk SA. Bipolar cases were over-represented in
      the high lethality risk group. BPRS anxiety-depressive cluster score was higher
      in unipolar than in bipolar cases. LIMITATIONS: The sample may not be
      representative of all patients with SA. The questionnaire has not been
      standardized for use in psychiatric populations. CONCLUSIONS: The higher
      proportion of high lethal risk SA in bipolar cases suggests that the risk of
      completed suicide is higher in bipolar disorder than in unipolar depression. The
      risk of lethality in SA was not associated with the intensity of symptoms of
      anxiety and depression.

PMID- 15555696
TI  - Compliance with SSRI medication during 6 months of treatment for major
      depression: an evaluation by determination of repeated serum drug concentrations.
AB  - BACKGROUND: A recent estimation in a psychiatric cohort showed numbers of
      noncompliance between 10% and 60%. Therapeutic drug monitoring (TDM) is one
      method assessing compliance by analysis of drug concentration in the blood.
      METHOD: During a 24-week phase IV clinical trial, five repeated serum samples of
      sertraline (SERT) and N-desmethylsertraline (DSERT), trough values in steady
      state, were collected per patient. Previous results show that the intraindividual
      variation over time of the ratio DSERT/SERT is low. Hence, we hypothesized that
      significant partial noncompliance could be scrutinized further by an assessment
      of the DSERT/SERT ratio. The main aim was to test the applicability of a novel
      type of TDM procedure based on repeated metabolite/parent compound ratio
      measurements. RESULT: 9.4% of the per-protocol population in the trial (n = 96)
      were in either hidden total (n = 4) or hidden partial (n = 5) noncompliance. Only
      by using the novel TDM ratio screening method could a majority of these patients
      be identified.

PMID- 15555697
TI  - Fish consumption and depression: the Northern Finland 1966 birth cohort study.
AB  - BACKGROUND: Since low fish consumption and omega-3 fatty acids have recently been
      linked with depression, we investigated by means of a large, general population
      database, whether a low fish consumption is associated with increased risk of
      developing depression. METHODS: The Northern Finland 1966 Birth Cohort was
      followed up prospectively from pregnancy up to the age of 31 years. The data on
      HSCL-25 depression subscale, doctor-diagnosed life-time depression and fish
      consumption (during the previous 6 months) of cohort members were obtained by
      postal questionnaires at the age of 31. The final number of cohort members, whose
      completed variable information was available in multivariate logistic analyses,
      was 2721 males and 2968 females. RESULTS: After adjusting for body mass index,
      serum total cholesterol level and socioeconomic situation, logistic regression
      analyses showed that among females the risk of developing depression increased up
      to 2.6-fold (95%CI 1.4-5.1) among rare fish eaters when compared with regular
      eaters. In males, there were no significant differences between rare and regular
      fish eaters for any of the estimates of depression. LIMITATIONS: The data on life
      time fish consumption of cohort members were not available. CONCLUSIONS: A low
      frequency of fish consumption was statistically significantly associated with
      depression in women, but not in men. Possible background-theories behind the
      gender difference are discussed.

PMID- 15555698
TI  - Neuropsychological functioning in major depression and responsiveness to
      selective serotonin reuptake inhibitors antidepressants.
AB  - BACKGROUND: Only two thirds of patients with major depression (MD) respond to
      antidepressants. Thus, far applicable predictors of responsiveness to selective
      serotonergic reuptake inhibitors (SSRIs) have not been found. Cumulative evidence
      linking serotonergic depletion and cognition led us to hypothesize that the
      neuropsychological functioning of major depression patients may predict their
      responsiveness to SSRI antidepressants. METHODS: Fifty-five patients meeting DSM
      IV criteria for major depression and strict inclusion and exclusion criteria
      underwent an extensive clinical and neuropsychological assessment prior to the
      initiation of selective serotonergic treatment. Following 6 weeks of treatment,
      severity of depression was reassessed, yielding a responsiveness score by which
      classification of each subject as a responder or nonresponder was made. The study
      was double blind. RESULTS: Logistic regression yielded neuropsychological
      indices, which significantly predicted the probability of depressed patients to
      respond favorably to SSRIs. Responders were characterized by better functioning
      in "simple" tasks and by worse functioning in "complex" tasks compared to
      nonresponders. No differences were found for more lateralized right or left
      hemisphere functions between responders and nonresponders. LIMITATIONS: Drug
      treatment comprised of SSRIs but was not standardized. Responsiveness was
      assessed following 6 weeks of treatment providing for initial amelioration rather
      than full remission. Placebo response was not controlled for. These limitations
      may influence the interpretation of the findings. CONCLUSIONS: The present
      findings suggest that responders and nonresponders to SSRIs might be
      distinguished by their neuropsychological functioning before treatment. If our
      findings are replicated, more efficient treatment might be practiced.

PMID- 15555699
TI  - Pathways to comorbidity: the transition of pure mood, anxiety and substance use
      disorders into comorbid conditions in a longitudinal population-based study.
AB  - BACKGROUND: To describe transitions to comorbidity within a 3-year period in
      three cohorts of subjects with at baseline a 12-month pure mood, anxiety or
      substance use disorder but no lifetime history of any other disorder category. To
      assess the role of personal and social vulnerability factors, life events,
      clinical factors and functional disability in the pathway to comorbidity.
      METHODS: Data were derived from the Netherlands Mental Health Survey and
      Incidence Study (NEMESIS), a prospective epidemiologic study of a representative
      sample of 7076 adults aged 18-65, interviewed in three waves (baseline, 1 and 3
      years after baseline) with the Composite International Diagnostic Interview.
      RESULTS: 15.2% of 99 pure mood, 10.5% of 220 anxiety and 6.8% of 192 substance
      use disorder cases became comorbid. Comorbid transition from pure mood disorder
      was multivariately associated with higher age, external mastery and severity of
      the disorder. Comorbidity developing from pure anxiety disorder was associated
      with past and recent stressful life circumstances (childhood trauma, negative
      life events) and physical functional disability. Predictors of comorbid
      transition from pure substance use disorder were personal and social
      vulnerability variables only (high neuroticism, low social support). LIMITATIONS:
      Although NEMESIS was performed among a substantial number of cases, the number of
      cases with a pure disorder at baseline subsequently developing comorbidity was
      low. This limited analysing determinants of different comorbid conditions.
      CONCLUSIONS: Risk factors for comorbid transitions vary depending on whether
      subjects have a primary mood, anxiety or substance use disorder. Interventions
      aimed at primary prevention of comorbidity to reduce psychiatric burden in
      populations with a history of pure disorders are indicated in response to clearly
      identified risk factors.

PMID- 15555700
TI  - Residual symptoms in depressed patients who successfully respond to short-term
      psychotherapy.
AB  - BACKGROUND: Most investigations of residual symptoms have focused on partial
      responders to antidepressant medications. Comparatively few have examined
      residual symptoms among patients who achieved a more successful response to
      treatment. In addition, few studies have assessed residual symptoms among
      patients treated with psychotherapy. The purpose of the present study was to
      assess residual symptoms of depression among psychiatric outpatients who
      successfully responded to psychotherapy and determine their association with
      other important clinical outcomes. METHODS: Sixty patients with major depression
      who participated in a randomized controlled trial of two forms of short-term,
      individual psychotherapy were studied. We examined the prevalence of residual
      symptoms among successful responders, as well as the relationships between
      residual symptoms, pre-therapy patient characteristics, relapse, and other
      outcomes. RESULTS: Thirty-three (55%) of the 60 patients responded successfully
      to psychotherapy. Of those, 82% had residual symptoms. Residual symptoms
      predicted relapse at 6-month follow-up, and were associated with less favorable
      psychosocial functioning at post-therapy and at 6-month follow-up. LIMITATIONS:
      The study consisted of post-hoc analyses of existing data, the number of
      asymptomatic patients was small, and a proxy measure of relapse was used.
      CONCLUSIONS: Residual symptoms are prevalent among depressed patients who
      successfully respond to psychotherapy. Greater residual symptoms appear to
      increase the risk for relapse and are associated with poorer psychosocial
      functioning.

PMID- 15555701
TI  - Decreased cortical gray and cerebral white matter in male patients with familial
      bipolar I disorder.
AB  - BACKGROUND: Previous MRI studies of bipolar disorder have failed to consistently
      demonstrate cortical gray or cerebral white matter tissue loss, as well as sulcal
      or ventricular enlargement. The inconsistencies are most likely due to the
      clinical and gender heterogeneity of the study populations as well as the
      different MRI acquisition and processing techniques. The objective of this study
      was to determine if there was a cortical gray matter and cerebral white matter
      deficit as well as sulcal and ventricular enlargement in a homogeneous sample of
      euthymic male patients with familial bipolar I disorder. METHODS: MRI tissue
      segmentation was utilized to obtain cortical gray matter, cerebral white matter,
      ventricular cerebrospinal fluid (CSF), and sulcal CSF volumes in 22 euthymic
      males with familial bipolar I disorder and 32 healthy male control subjects.
      RESULTS: Relative to the controls, the familial bipolar I patients demonstrated:
      (1) significant reductions of both cortical gray matter and cerebral white matter
      volumes; and (2) significant increases in both sulcal and ventricular CSF
      volumes. In the bipolar group, there was a significant negative correlation
      between cortical gray matter volume and sulcal CSF volume. LIMITATIONS: Small
      sample size, retrospective interviews, possible medication effects. CONCLUSIONS:
      These results provide evidence for significant cortical gray matter and cerebral
      white matter deficits and associated sulcal and ventricular enlargement in
      euthymic males with familial bipolar I disorder.

PMID- 15555702
TI  - The dexamethasone suppression test as a predictor of suicidal behavior in
      unipolar depression.
AB  - BACKGROUND: Non-suppression on the dexamethasone suppression test (DST) in
      unipolar depression has been found to be associated with completed suicide, with
      less consistent data for attempted suicide and hospitalizations for suicidality.
      The purpose of this study was to examine DST non-suppression as a predictor of
      these three aspects of suicidal behavior. METHODS: Records were reviewed for 101
      patients who met criteria for major depressive disorder and/or dysthymic disorder
      and had a DST performed. All patients were treated naturalistically and were
      followed for an average of 2 years. DST suppressors and non-suppressors were
      compared with respect to three outcomes: (1) completed suicide; (2) attempted
      suicide; and (3) hospitalizations for suicidality. RESULTS: DST non-suppressors
      were significantly more likely to have completed suicide or be hospitalized for
      suicidality than DST suppressors, with a non-significant trend for attempts.
      Total suicidal events were also significantly more frequent in the non-suppressor
      group. LIMITATIONS: Axis II diagnoses and severity of illness were not assessed.
      Knowledge of DST results may have influenced the decision to hospitalize
      patients. CONCLUSIONS: DST non-suppression identifies unipolar depressed patients
      with a higher risk for future suicide completion or hospitalization for
      suicidality. Performance of DST upon initiation of treatment may be a useful
      adjunct in identifying suicidal risk.

PMID- 15555703
TI  - No psychomotor slowing in fine motor tasks in dysthymia.
AB  - INTRODUCTION: Few studies using objective and sensitive measuring techniques have
      investigated whether psychomotor retardation (PR), an important symptom of a
      major depressive disorder (MDD), is also present in dysthymic patients. In this
      study, the following questions were addressed: (1) is PR also prevalent in
      dysthymia? (2) If so, is the PR cognitive or motor in nature? And (3) does the
      nature and degree of the PR in patients with dysthymia differ from the PR in MDD
      patients found in earlier studies? METHODS: PR was measured by comparing the,
      digitally recorded, fine motor performance of 20 unmedicated dysthymic inpatients
      (mean age: 33) and 32 controls on copying and drawing tasks. In addition, the
      performance of the dysthymic patients was compared to the performance results of
      32 unmedicated MDD inpatients collected in an earlier study. RESULTS: The
      dysthymic patients were not slower than the controls in performing the fine motor
      tasks: neither initiation time (IT) nor movement time (MT) were prolonged. As
      expected, the MDD patients did show significantly longer ITs and MTs in all tasks
      compared to the controls. On the clinical Salpetriere Retardation Rating Scale
      (SRRS), the dysthymic patients had high scores on mainly subjective cognitive
      items like concentration and memory complaints. LIMITATIONS: The dysthymic
      patients had significantly less severe forms of depression compared to the MDD
      patients. As dysthymia, by definition, is a less severe form of depression we
      could not examine whether PR would manifest itself in severely depressed
      dysthymic patients, as is the case in certain MDD patients. CONCLUSION: In this
      study, no objective evidence was found for PR in dysthymic patients during fine
      motor tasks. PR may be used to differentiate between dysthymia and MDD.

PMID- 15555704
TI  - Electroconvulsive therapy in depressive illness that has not responded to drug
      treatment.
AB  - BACKGROUND: Antidepressant medication resistance is the commonest indication for
      electroconvulsive therapy (ECT) in Scotland. Evidence from the USA suggests that
      clinical response is reduced for medication resistant patients. The aim of the
      present study was to establish if the American results were generalisable to
      routine clinical practice in Edinburgh. METHOD: Fifty eligible depressed patients
      consecutively referred for a new course of bilateral ECT at the Royal Edinburgh
      Hospital were prospectively assessed as part of the National Audit of ECT in
      Scotland. The patients were categorised into those who had received adequate drug
      treatment pre-ECT (and could therefore be classed as medication resistant) and
      those who had not, using five operational definitions. The clinical response of
      the ECT was then compared between groups, using the Montgomery-Asberg Rating
      Scale for Depression (MADRS) and Clinical Global Impression Scale (CGI). RESULTS:
      Patients defined as medication resistant had an identical response to patients
      who were not defined as medication resistant (in both groups 60% met the
      predetermined criterion for clinical response), and this was consistent across
      the five operational definitions. CONCLUSIONS: The hypothesis that medication
      resistance is associated with a reduced probability of clinical response to ECT
      was not supported. LIMITATIONS: Some patients who were inadequately drug treated
      might have proven eventually to be medication resistant, which would have
      obscured a potential difference in clinical response. It is not known how
      generalisable the results are to clinical practice in the rest of the UK.

PMID- 15555705
TI  - Incident hypertension associated with depression in the Baltimore Epidemiologic
      Catchment area follow-up study.
AB  - BACKGROUND: This study evaluates the role of depression as a specific risk factor
      for hypertension. METHODS: This study analyzed the prospective data in the
      Baltimore Epidemiologic Catchment Area (ECA) Follow-up Study (n=1920), a
      longitudinal population-based study of mental illness in East Baltimore. Incident
      cases of hypertension as assessed by self-report (n=148) in 1993 were compared to
      the remaining cohort without hypertension (n=901) across three waves of ECA
      interviews (1981, 1982, 1993). Depression and related symptoms were measured at
      baseline (1981) by the Diagnostic Interview Schedule (DIS) and categorized as
      dysphoria, dysthymia, or major depressive episode (MDE) according to Diagnostic
      and Statistical Manual (DSM) III criteria. RESULTS: Individuals with a major
      depressive episode compared to those who reported never having dysphoria had a
      marginally significant increased risk for hypertension (Odds Ratio (OR)=2.16; 95%
      Confidence Interval (CI) (0.94,4.98)) after adjustment for age, gender, race,
      body mass index, Nam-Powers socioeconomic score, alcohol usage, smoking,
      exercise, diabetes status, and number of general medical visits. MDE reported to
      have begun more than a year before the baseline measurement was associated with
      an increased risk for incident hypertension (Adjusted OR=3.67, 95% CI
      (1.25,10.79). LIMITATIONS: Potential misclassification of self-reported
      hypertension outcome. CONCLUSIONS: Even though the data are based on self-report
      of hypertension, these findings suggest that depression may be an independent
      risk factor for hypertension particularly for those with recurrent episodes or a
      long term history of the disease.

PMID- 15555706
TI  - Prevalence and risk indicators of depression in elderly nursing home patients:
      the AGED study.
AB  - BACKGROUND: Depression is a common and disabling psychiatric disorder in later
      life. Particular frail nursing home patients seem to be at increased risk.
      Nursing home-based studies on risk indicators of depression are scarce. METHODS:
      Prevalence and risk indicators of depression were assessed in 333 nursing home
      patients living on somatic wards of 14 nursing homes in the North West of the
      Netherlands. Depressive symptoms were measured by means of the Geriatric
      Depression Scale (GDS). Major and minor depression were diagnosed according to
      the DSM-IV criteria, sub-clinical depression was defined as a GDS score >10 while
      not meeting the DSM-V criteria for depression. RESULTS: The prevalence of major
      depression was assessed to be 8.1% and the prevalence of minor depression was
      14.1%, while a further 24% of the patients suffered from sub-clinical depression.
      For major depression significant risk indicators were found for pain, functional
      limitations, visual impairment, stroke, loneliness, lack of social support,
      negative life events and perceived inadequacy of care. For sub-clinical
      depression the same risk indicators were found, with the exception of lack of
      social support. LIMITATIONS: Data were collected cross-sectional. CONCLUSIONS:
      The prevalence of depression in the nursing home population is very high.
      Whichever way defined, the prevalence rates found were three to four times higher
      than in the community-dwelling elderly. Age, pain, visual impairment, stroke,
      functional limitations, negative life events, loneliness, lack of social support
      and perceived inadequacy of care were found to be risk indicators for depression.
      Consequently, optimal physical treatment and special attention and focus on
      psychosocial factors must be major goals in developing care programs for this
      frail population.

PMID- 15555707
TI  - Factors associated with depressive symptoms among 18-year-old boys: a prospective
      10-year follow-up study.
AB  - BACKGROUND: The aim is to study associative and predictive factors for self
      reported depressive symptoms among 18-year-old boys. METHODS: The participants in
      this community-based 10-year follow-up study consisted of 2348 boys born during
      1981. At baseline, three informant sources were used: parents, teachers, and the
      children themselves. At follow-up, self-report questionnaires were used to study
      boys' family factors, life events, adaptive functioning, and substance use.
      Depressive symptoms at age 18 were established using Beck's Depression Inventory
      (BDI). RESULTS: Poor adaptive functioning within family and in education, having
      fewer than two close friends, somatic health problems, and using illicit drugs
      were all independently associated with a high level of depressive symptoms in the
      cross-sectional data at age 18. Self-reported depressive symptoms (Children's
      Depression Inventory, CDI) at age 8 independently predicted an increased number
      of depressive symptoms 10 years later. LIMITATIONS: Only self-reported
      questionnaires were used at follow-up. CONCLUSIONS: The high association between
      depressive symptoms at age 8 and at age 18 gives grounds for paying special
      attention to children's own intimations of distress already in the early school
      years. Using self-report screening questionnaires in school health care may help
      identify children's depressive symptoms.

PMID- 15555708
TI  - Depression in older persons with versus without vascular disease in the open
      population: similar depressive symptom patterns, more disability.
AB  - BACKGROUND: Clinical studies suggest that vascular depression presents with
      typical symptom patterns. The aim of the present study is to examine whether
      depressed older persons in the open population with and without vascular disease
      show different symptom patterns. METHODS: In the Longitudinal Aging Study
      Amsterdam (LASA), a depressed cohort with (n=114) and without (n=292) vascular
      disease was identified. Depression was measured using self-reports (CES-D).
      Vascular disease was confirmed or ruled out using a combination of self-reported
      data, medication use and reports from general practitioners. RESULTS: No
      significant differences were found in depressive symptom patterns, in symptom
      clusters nor individual items of the CES-D. Depressed subjects with vascular
      disease showed much more disability than those without vascular disease. Age of
      onset of depression did not show statistically significant difference.
      CONCLUSIONS: From our study in the open population, there is no evidence to
      support the hypothesis that depressed older persons with vascular disease have a
      distinct depressive symptom profile, but they do show more disability.

PMID- 15555709
TI  - Ethnic differences in first clinical presentation of bipolar disorder: results
      from an epidemiological study.
AB  - BACKGROUND: Although high incidence rates of mania have been described in some
      ethnic minority populations, little is known about any ethnic differences in the
      early clinical presentation of bipolar disorder. METHODS: All cases of
      operationalised DSM-IV bipolar I disorder (BPI), first manic episode, within a
      defined epidemiological catchment area over a 35-year period, were identified;
      sociodemographic data, including ethnicity, and clinical information were then
      extracted. The proportion of African-Caribbean (n=52), African (n=33) and white
      European (n=149) cases who experienced a depressive episode before onset of mania
      and psychotic symptoms at first mania were compared. RESULTS: African-Caribbean
      and African groups were significantly less likely to have experienced a
      depressive episode before onset of first mania, at 13.5% and 6.1%, respectively,
      compared with 28.1% in the white European group. African-Caribbean and African
      groups also experienced more severe psychotic symptoms at first mania, but there
      were no differences in mood incongruent or first rank symptoms between ethnic
      groups. LIMITATIONS: Data pertaining to diagnosis and clinical symptoms were
      extracted by retrospective case note review. CONCLUSIONS: Ethnic differences in
      clinical presentation of bipolar disorder may have implications for assessment
      and treatment of ethnic minority patients.

PMID- 15555710
TI  - Antidepressant drug use in Lombardy, Italy: a population-based study.
AB  - BACKGROUND: The patterns of antidepressant drug prescribing have rarely been
      studied in large and geographically defined catchment areas. In the present
      study, we examined the prevalence and distribution of antidepressant prescribing
      in Lombardy, a northern Italy region of nine million inhabitants. METHODS: This
      study used the Regional Administrative Database of Lombardy. This database
      includes all prescriptions reimbursed by the National Health System in the
      population living in this region. All antidepressant prescriptions dispensed from
      the 1st January to the 31st December 2001 were extracted and prevalence data
      calculated by dividing antidepressant users by the total number of male and
      female residents in each age group. RESULTS: During the study period, 404,238
      individuals were dispensed antidepressants, yielding a prevalence of use of 2.85
      (95% confidence interval 2.84, 2.87) per 100 males and 5.92 (95% confidence
      interval 5.90, 5.94) per 100 females. The prevalence of use progressively rose
      with age in both sexes, with the highest rates in old and very old individuals.
      The majority of individuals received a pharmacological treatment with selective
      serotonin reuptake inhibitors only, slightly more than 12% received a treatment
      with tricyclic antidepressants. General practitioners issued the majority of
      antidepressant prescriptions. CONCLUSIONS: The very high rates of antidepressant
      drug prescribing detected in late life suggest the need of characterising these
      individuals in terms of medical and psychiatric characteristics, needs and
      quality of life. It also suggests the need for pragmatic clinical trials, carried
      out in the general practice, with the aim of assessing whether antidepressants
      are effective in these conditions.

PMID- 15555711
TI  - Public attitudes to people with depression: have there been any changes over the
      last decade?
AB  - BACKGROUND: A consistent finding of representative surveys that were conducted in
      Germany in the early 1990s was that people with depression encountered a
      substantial amount of stigma and discrimination. The aim of this study was to
      examine whether public attitudes have improved over the last decade or not.
      METHODS: In 2001, a representative survey was carried out among the adult
      population of the "old" Federal Republic of Germany using the same methodology as
      in a previous survey in 1990. RESULTS: Regarding emotional reactions of the
      respondents towards people with depression, our findings are inconsistent. While
      there has been an increase in the readiness to feel pity and also a slight
      increase in the tendency to react aggressively, the expression of fear remained
      unchanged. The public's desire for social distance from people with depression
      was as strong in 2001 as it had been in 1990. CONCLUSION: The hypothesis of a
      change for the better regarding public attitudes towards depressed people is not
      supported by our findings. Further efforts are needed to reach this goal.

PMID- 15555712
TI  - Bone mineral density during maintenance treatment with supraphysiological doses
      of levothyroxine in affective disorders: a longitudinal study.
AB  - BACKGROUND: This prospective study was designed to determine whether patients
      with prophylaxis-resistant affective disorders, receiving adjunctive maintenance
      therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of
      accelerated bone loss compared to the reference population database. METHODS: In
      21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and
      femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy
      X-ray absorptiometry (DXA). BMD measurement was performed first after patients
      had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean
      dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4
      (mean dose=416 mcg/d) therapy. RESULTS: There was no statistically significant
      difference between the actual percentage decline in bone mineral density and the
      expected percentage decline in any of the measured bone regions. In a stepwise
      linear regression analysis, age was identified as a predictor of percentage
      change in BMD. After controlling for age, the only other variable that showed a
      consistent trend was the dose of L-T4, with higher doses being positively
      correlated with the percentage decline of BMD. LIMITATIONS: Relatively small
      sample size, no bone density assessment prior to treatment with L-T4, no patient
      control group with mood disorders who did not receive L-T4 treatment, and bone
      density follow-up intervals were variable. CONCLUSIONS: This study did not
      demonstrate evidence that long-term treatment of affectively ill patients with
      supraphysiological doses of L-T4 significantly accelerates loss of bone mineral
      density compared to the age-matched reference population. However, the decline of
      BMD in one individual patient underscores that caution is indicated and that
      regular assessment of BMD during longer-term supraphysiological thyroid hormone
      treatment is needed.

PMID- 15555713
TI  - Cognitive complexity of self-administered depression measures.
AB  - BACKGROUND: Self-administered depression measures are important tools for
      research and practice, but their utility depends on the quality of the
      measurements they yield. Respondent comprehension is essential for meaningful
      measurement and prior studies have used readability indices to assess
      comprehensibility. Readability, however, is only one aspect of comprehension and
      empirical evidence shows that comprehension and measurement quality decrease as
      the cognitive complexity of standardized questions increases. Thus, cognitive
      complexity may provide a useful guide for selecting measures to maximize
      measurement quality. METHODS: This study compared the cognitive complexity of 15
      self-administered depression measures. Four aspects of cognitive complexity
      (length, readability, linguistic problems and number) were combined to
      characterize overall complexity. RESULTS: Measures varied considerably. The most
      cognitively complex measures, likely to be most difficult to comprehend, were the
      Inventory to Diagnose Depression (IDD), the Hamilton Depression Inventory (HDI,
      Full and Short Versions), and the Beck Depression Inventory (BDI, BDI-II, BDI
      PC). The least complex measures, likely to be easiest to comprehend, were the
      Harvard National Depression Screening Day Scale (HANDS), the Revised Hamilton
      Rating Scale for Depression Self-Report Problem Inventory (RHRSD) and the Zung
      Self-Rated Depression Scale (SDS). This multidimensional approach to assessing
      complexity and comprehensibility yielded different results than readability
      indices alone. LIMITATIONS: This study did not include all self-administered
      depression measures and did not examine the relationship of cognitive complexity
      to actual responses to depression measures. CONCLUSIONS: Since cognitive
      complexity is likely to limit comprehension and reduce measurement accuracy, it
      merits consideration in selection of self-administered depression measures.

PMID- 15555714
TI  - Expressed emotion versus relationship quality variables in the prediction of
      recurrence in bipolar patients.
AB  - BACKGROUND: The expressed emotion (EE) construct has predicted clinical outcomes
      in schizophrenia and depression, but few studies have been conducted with bipolar
      patients. Moreover, there is a particular dearth of information regarding the
      prediction of depressive versus manic episodes in bipolar patients. Questions
      also remain about the utility of EE compared to other variables (perceived
      criticism, relationship negativity, and chronic strain in close relationships)
      that more directly evaluate interpersonal stress and about specific predictions
      of mania or depression. METHODS: Forty-seven outpatients with bipolar I disorder
      participated in a 1-year longitudinal study. A close collateral of the patient
      completed the Five Minute Speech Sample (FMSS) to assess EE, and participants
      completed perceived criticism and negativity ratings of collaterals. Clinical
      outcomes and chronic interpersonal stress were assessed by interview at 3-month
      intervals. RESULTS: High EE predicted depressive, but not manic recurrence. Other
      variables of close interpersonal relationships were not significant predictors of
      recurrence. LIMITATIONS: Participants nominated collaterals, and those who did
      not have such a confidant were excluded. CONCLUSIONS: The FMSS was sensitive to
      even mild negativity by the collateral that predicted later depressive episodes.
      This is the first study to demonstrate polarity-specific effects of EE on the
      prediction of recurrence in bipolar disorder.

PMID- 15555715
TI  - Absence of gender differences in pediatric bipolar disorder: findings from a
      large sample of referred youth.
AB  - BACKGROUND: Because little is known about gender differences in pediatric bipolar
      disorder, we evaluated whether gender moderates the expression of pediatric
      bipolar disorder in a large clinical sample. METHODS: Subjects were consecutively
      referred youth aged 18 years or less who met full criteria for DSM-III-R bipolar
      disorder (BPD) (females, n=74; BD males, n=224). All subjects were assessed with
      a structured diagnostic interview and measures of psychosocial and family
      functioning. RESULTS: Most of the bipolar subjects (91% of males, 70% of females)
      also had ADHD. Bipolar disorder was equally prevalent in both genders. Among
      females and males, severe irritability (83% and 80%, respectively), mixed
      presentation (87% and 84%, respectively), chronic course (84% and 77%,
      respectively) and prepubertal onset (78% and 93%, respectively) predominated the
      clinical picture. We found no meaningful differences between genders in the
      number of BPD symptoms, type of treatment for BPD (counseling, medication,
      hospitalization), severity of educational deficits, severity of family and
      interpersonal functioning or patterns of psychiatric comorbidity. CONCLUSIONS:
      Because gender does not moderate the clinical expression of pediatric bipolar
      disorder, our data does not suggest that gender specific criteria for the
      disorder are warranted.

PMID- 15555716
TI  - The relationship between duration of labour, time of delivery, and puerperal
      psychosis.
AB  - BACKGROUND: Puerperal psychosis is the most serious psychiatric disorder after
      childbirth. Despite the ongoing debate regarding its diagnostic status, there is
      increasing evidence that it is related to bipolar or schizoaffective disorder.
      Although a well-recognized precipitant of mania, the role of sleep loss has not
      been systematically studied in the onset of puerperal psychosis. The aim of this
      study was to test the hypothesis that sleep disruption resulting from longer
      labour or nighttime delivery would be associated with the onset of puerperal
      psychosis. METHOD: Data on duration of labour and time of delivery were compared
      between a group of patients who were hospitalized with a diagnosis of puerperal
      psychosis and a group of controls from the same hospitals that were matched on
      age, parity, and on year of admission to the hospital. RESULTS: The most common
      DSM-IV diagnoses were bipolar disorder or schizoaffective disorder. The women in
      the puerperal psychosis group had a longer duration of labour and were more
      likely to have a nighttime delivery compared to women in the control group.
      Insomnia was the most frequent and usually the earliest symptom. LIMITATIONS:
      Small sample size, chart review, no direct measure of sleep, and use of a normal
      control rather than a comparison group of at-risk women. CONCLUSIONS: These
      preliminary findings provide indirect evidence that sleep loss may be a
      precipitant of puerperal psychosis in women who are biologically predisposed to
      this illness. DECLARATION OF INTEREST: This research was supported by the Ontario
      Mental Health Foundation.

PMID- 15555717
TI  - Burden, reward and family functioning of caregivers for relatives with mood
      disorders: 1-year follow-up.
AB  - BACKGROUND: Longitudinal caregiver studies of patients with mood disorders report
      no consistent pattern in burden over time. This naturalistic study of caregivers
      of patients with mood disorders assesses caregiver perceptions of burden, reward
      and family functioning at hospitalization and at 1 year follow-up. METHODS:
      Thirty-nine caregivers of patients with mood disorders were recruited during
      their relative's in-patient psychiatric hospitalization. Caregivers were given an
      assessment packet to complete at the time of enrollment and identical assessment
      packets were mailed to the caregivers at 1 year. RESULTS: Caregivers of bipolar
      disorder relatives reported less reward, more subjective burden and worse family
      functioning than depression caregivers, at recruitment. Bipolar caregivers showed
      a significant reduction in burden 1 year after their relative was discharged from
      the hospital, whereas depression caregivers showed no change at 1 year. At 1
      year, overall family functioning was unchanged and was in the unhealthy range in
      all dimensions except for behavior control. Limitations of the study include the
      small sample size, the selective recruitment from a hospital setting where family
      members did not actively seek out help and the high drop-out rate. CONCLUSIONS:
      Caregivers of relatives with mood disorders show a different pattern of burden
      and reward, over time, depending on the patient diagnosis. In all cases, however,
      family functioning was significantly impaired. CLINICAL RELEVANCE: Short-term
      family interventions can be offered at the time of hospitalization to try to
      reduce caregiver burden and increase caregiver reward.

PMID- 15555718
TI  - Temperament and depressive symptoms: a population-based longitudinal study on
      Cloninger's psychobiological temperament model.
AB  - BACKGROUND: This study examined whether temperament dimensions, as indicated by
      Cloninger's psychobiological model [Cloninger, C.R., Svrakic, D.M., Przybeck,
      T.R., 1993. A psychobiological model of temperament and character. Arch. Gen.
      Psychiatry 50, 975-990.], predicted depressive symptoms across a 4-year follow
      up. METHODS: Nine hundred ninety-three women and 583 men from the on-going
      population-based study of "Cardiovascular Risk in Young Finns" completed the
      Temperament and Character Inventory (TCI) [Cloninger, C.R., Svrakic, D.M.,
      Przybeck, T.R., 1993. A psychobiological model of temperament and character.
      Arch. Gen. Psychiatry 50, 975-990.], a revised version of Beck's Depression
      Inventory [Beck, A.T., Steer, R.A., 1987. Manual for the Revised Beck Depression
      Inventory. Psychological Corporation, San Antonio, TX; Katainen, S., Raikkonen,
      K., Keltikangas-Jarvinen, L., 1999. Adolescent temperament, perceived social
      support and depressive tendencies as predictors of depressive tendencies in young
      adulthood. Eur. J. Pers. 13, 183-207] and the Perceived Social Support Scale-R
      [Blumenthal, J.A., Burg, M.M., Barefoot, J., Williams, R.B., Haney, T., Zimet,
      G., 1987. Social support, type A behavior, and coronary artery disease.
      Psychosom. Med. 49, 331-340]. RESULTS: Results of hierarchical linear regression
      models showed that the temperament subscales impulsiveness, shyness with
      strangers, fatigability, sentimentality, and persistence increased the risk of
      depressive symptoms independently of a wide variety of known risk factors for
      depression. The association between fatigability and depressive symptoms was
      stronger for participants with low social support than for those reporting high
      social support. LIMITATIONS: The sample was restricted to men and women aged 20
      35 at baseline and no clinically significant cut-point for depression was
      defined. CONCLUSIONS: Our results strengthen the view that depressive symptoms
      are independently influenced by temperamental dispositions.

PMID- 15555719
TI  - A comparative study of milnacipran and paroxetine in outpatients with major
      depression.
AB  - BACKGROUND: Milnacipran is a dual-action antidepressant which inhibits both
      serotonin and noradrenaline reuptake with no affinity for any neurotransmitter
      receptor studied. METHODS: A 6-week double-blind multicentre study compared
      milnacipran (100 mg/day) with paroxetine (20 mg/day) in 300 outpatients with
      major depression. Efficacy was evaluated using HAMD17, MADRS and CGI for severity
      of illness and global improvement. Data were analysed on an intention to treat,
      last observation carried forward, basis. RESULTS: Milnacipran and paroxetine were
      both effective and well tolerated with no significant difference in their
      effects. After treatment discontinuation, milnacipran was associated with
      significantly less emergent symptoms. Responders, at endpoint, to milnacipran had
      significantly greater levels of psychomotor retardation at baseline than non
      responders. LIMITATIONS: The study did not include a placebo group so that it is
      impossible to determine absolute levels of efficacy. CONCLUSIONS: Both
      milnacipran and paroxetine were effective and well tolerated by outpatients with
      major depression treated for 6 weeks. After treatment discontinuation milnacipran
      was associated with less emergent symptoms. Psychomotor retardation at baseline
      may be a predictive factor of a favourable response to milnacipran.

PMID- 15555720
TI  - Depression with atypical features in a sample of primary care outpatients:
      prevalence, specific characteristics and consequences.
AB  - BACKGROUND: In the context of the current debate on the clinical relevance of
      atypical depression, the present study investigated the prevalence and specific
      characteristics of the disorder in depressed primary care outpatients and
      compared patients with atypical and with the prototypical form of depression
      ("non-atypical" depression). METHODS: 403 patients were examined using the
      Composite International Diagnostic Interview, Inventory of Depressive
      Symptomatology, Hamilton Depression Scale and DSM-IV criteria. Configurational
      frequency analyses (CFA) were conducted to identify non-random configurations of
      symptoms. Moreover, tests for independent sample comparisons were applied.
      RESULTS: The prevalence of atypical depression in our sample of depressed
      patients was 26.3%. CFA revealed one significant symptom pattern: mood reactivity
      without additional atypical features (p<0.000001). A significant difference
      emerged between patients suffering from atypical versus non-atypical depression
      in terms of severity (p< or =0.001). LIMITATIONS: The sample size was modest.
      CONCLUSIONS: A considerable proportion of depressed primary care outpatients may
      suffer from atypical depression which may contribute to under-recognition of
      depression in primary care. Results of CFA indicated the significance of mood
      reactivity which may also occur in depressed patients without additional atypical
      symptoms. Patients with atypical depression may suffer from less severe
      depression as compared to patients with non-atypical depression.

PMID- 15555721
TI  - Psychosocial morbidity and its correlates in cancer patients of the Mediterranean
      area: findings from the Southern European Psycho-Oncology Study.
AB  - BACKGROUND: A few and partial data are available on psychosocial morbidity among
      cancer patients in Mediterranean countries. As a part of a more general
      investigation (Southern European Psycho-Oncology Study-SEPOS), the rate of
      psychosocial morbidity and its correlation with clinical and cultural variables
      were examined in cancer patients in Italy, Portugal and Spain. METHODS: A
      convenience sample of cancer outpatients with good performance status and no
      cognitive impairment were approached. The Hospital Anxiety-Depression scale (HAD
      S), the Mini-Mental Adjustment to Cancer scale (Mini-MAC), and the Cancer Worries
      Inventory (CWI) were used to measure psychological morbidity, coping strategies
      and concerns about illness. RESULTS: Of 277 patients, 34% had pathological scores
      ("borderline cases" plus "true cases") on HAD-S Anxiety and 24.9% on HAD-S
      Depression. Total psychiatric "caseness" was 28.5% and 16.6%, according to
      different HAD cut-offs (14 and 19, respectively). Significant relationships of
      HAD-S Anxiety, HAD-S Depression, HAD-S Total score, with Mini-MAC Hopeless and
      Anxious Preoccupation, and CWI score were found. No differences emerged between
      countries on psychosocial morbidity, while some differences emerged between the
      countries on coping mechanisms. Furthermore, Fatalism, Avoidance and marginally
      Hopeless were higher compared to studies carried out in English-speaking
      countries. LIMITATIONS: The relatively small sample size and the good performance
      status prevent us to generalize data on patients with different cancer sites and
      advanced phase of illness. CONCLUSIONS: One-third of the patients presented
      anxiety and depressive morbidity, with significant differences in characteristics
      of coping in Mediterranean countries in comparison with English-speaking
      countries.

PMID- 15555722
TI  - Kindling and behavioral sensitization: are they relevant to recurrent suicide
      attempts?
AB  - BACKGROUND: Data from a sample of suicidal young adults were used to examine the
      relevance of the kindling and behavioral sensitization models to suicide
      attempts. Three predictions derived from the kindling and sensitization models
      were tested: a higher number of suicide attempts would be associated with (a)
      lower levels of pre-attempt stress; (b) higher suicidal intent; and (c) greater
      lethality of the current attempt. METHODS: Measures of life stress and suicidal
      intent were collected among 123 young adults who attempted suicide just prior to
      entering treatment. Data on the total number of suicide attempts and the
      lethality of the current attempt were also collected. RESULTS: Number of suicide
      attempts was significantly and positively associated with pre-suicidal crisis
      life stress and suicidal ideation, but was not significantly associated with
      lethality of the most recent attempt. LIMITATIONS: The young sample drawn from a
      military medical setting may not accurately represent suicide attempters in the
      general population. Only total negative life events in the year preceding suicide
      attempt were examined, not the increase in negative life events immediately prior
      to suicide attempt. CONCLUSIONS: The kindling and sensitization models may not
      accurately describe the progression of recurrent suicide attempts.

PMID- 15555723
TI  - Affective state and EEG sleep profile in response to rapid tryptophan depletion
      in recently recovered nonmedicated depressed individuals.
AB  - BACKGROUND: The current study examines whether a tryptophan-free amino acid drink
      (TFD) causes a transient mood relapse in unmedicated patients recently recovered
      from major depression. TFD is thought to reduce cerebral serotonin, a
      neurotransmitter implicated in depression. Some studies report that TFD reverses
      the antidepressant and REM-suppression effects of selective serotonin reuptake
      inhibitors (SSRIs). METHODS: Following an average of 10 weeks of Cognitive
      Behavioral Therapy (CBT), 13 recovered patients who achieved 50% or greater
      reduction on the initial Hamilton Rating Scale of Depression (HRSD) underwent a
      double-blind challenge with the TFD and a control drink. In order to demonstrate
      the central physiological effects of the TFD on REM sleep in these patients, all
      night polygraphic sleep recordings were obtained before and after the TFD and
      control drink. RESULTS: Relative to the control drink, TFD decreased REM latency
      and plasma concentrations of tryptophan but had no statistically significant
      effect on mood symptoms as measured by the HRSD, Beck Depression Inventory (BDI),
      and Profile of Mood States (POMS). LIMITATIONS: High participant attrition, a
      physiologically active control drink, physical side effects in response to both
      drinks, and low statistical power may be methodological considerations that limit
      interpretation of findings. CONCLUSIONS: The failure to find a transient mood
      relapse after the TFD may suggest that: (a) nonpharmacological recovery from
      depression does not occur via serotonergic mechanisms, (b) participant variables
      may be operating, or (c) CBT alters psychological responses to unfavorable
      biological states.

PMID- 15555724
TI  - Efficacy and safety of long-acting risperidone in stable patients with
      schizoaffective disorder.
AB  - BACKGROUND: The treatment of schizoaffective disorder is often complicated by the
      variety of symptoms that contribute to its pathology. Data from a large study
      (n=725), which included schizoaffective patients to assess the effect of long
      acting risperidone, are presented. METHOD: A multicenter, open-label study
      enrolled non-acute, clinically stable patients with schizoaffective disorder
      (n=110). Patients on a stable dose of antipsychotic for at least 4 weeks at study
      entry were switched to long-acting risperidone every 2 weeks for 50 weeks.
      RESULTS: Mean Positive and Negative Syndrome Scale (PANSS) total scores (+/-S.E.)
      improved significantly (p<0.001) at each measured time point, including endpoint
      (-9.0+/-1.6), compared with baseline. Significant reductions were observed on
      mean PANSS cluster scores for both anxiety/depression (-1.3+/-0.4, p<0.001) and
      uncontrolled hostility/excitement (-0.7+/-0.3, p<0.05). In addition, scores
      improved significantly for positive symptoms (-2.2+/-0.5, p<0.001), negative
      symptoms (-3.1+/-0.5, p<0.001), and disorganized thoughts (-1.7+/-0.4, p<0.001).
      The overall subjective score of movement disorders was low at baseline (3.6+/
      4.1) and had significantly decreased at endpoint (2.75; p<0.05). Patients were
      previously treated with antipsychotics for 398+/-790 days before being switched
      to long-acting risperidone. LIMITATIONS: Although this was a 50-week study, which
      included over 100 patients with schizoaffective disorder, limitations include the
      open-label design and that it was not designed specifically to assess patients
      with this disorder. PANSS symptom domains previously defined by factor analytic
      methods were used for mood symptom measures. No specific mood symptom scales were
      administered in this study. CONCLUSION: Patients with schizoaffective disorder,
      considered stable on their antipsychotic medication at study entry, experienced
      additional significant clinical improvements and minimal side effects with
      injections of long-acting risperidone over a 50-week study period.

PMID- 15555725
TI  - An open-label trial of olanzapine for corticosteroid-induced mood symptoms.
AB  - BACKGROUND: Prescription corticosteroids are given for a variety of common
      medical conditions. Psychiatric symptoms including depression, psychosis, and
      especially mania are common side effects of corticosteroid therapy. However,
      minimal data are available on the treatment of corticosteroid-induced psychiatric
      symptoms. METHOD: In this study, 12 outpatients with manic or mixed symptoms
      secondary to corticosteroids were enrolled in a 5-week prospective, open-label
      trial of olanzapine. Psychiatric symptom measures included the Hamilton Rating
      Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief
      Psychiatric Rating Scale (BPRS). Side effects were monitored with the Simpson
      Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes
      Akathisia Scale (BAS). Weight and blood glucose were obtained at baseline and
      exit. Olanzapine dosing was flexible beginning at 2.5 mg/day and titrated upward
      as necessary to a maximum dose of 20 mg/day. Data were analyzed with Wilcoxon
      signed rank tests using baseline and exit data on all 12 participants. RESULTS:
      Participants showed significant reductions in YMRS (primary outcome measure),
      HRSD, and BPRS scores with no significant change in the SAS, AIMS, BAS, weight,
      or blood glucose levels. One participant discontinued early due to lack of
      efficacy. CONCLUSION: These data suggest that olanzapine is well tolerated and
      appears to be useful for mood disturbances associated with corticosteroid
      therapy. Controlled trials seem warranted to confirm these observations.

PMID- 15555726
TI  - Treatment-response by age at onset in obsessive-compulsive disorder.

PMID- 15555727
TI  - Social navigation hypothesis of depression revisited.

PMID- 15555728
TI  - RNA interference targeting cathepsin L and Z-like cysteine proteases of
      Onchocerca volvulus confirmed their essential function during L3 molting.
AB  - We describe the successful use of RNA interference (RNAi) to investigate gene
      function in the human filarial parasite Onchocerca volvulus third-stage larvae
      (L3). We targeted two specific gene products, the O. volvulus cathepsin L (Ov
      CPL) and cathepsin Z-like (Ov-CPZ) cysteine proteases, which were proposed to
      function during O. volvulus L3 molting. We show that fluorescent-labeled Cy3
      dsRNA corresponding to cpl or cpz regions encoding the mature enzymes can enter
      the larvae. The molting rate of larvae treated overnight with 0.5 mg ml(-1) cpl
      was reduced by 92% and 86% in comparison to normal control worms. It appeared
      that although the larvae started the molting process the last stage of molting,
      ecdysis was inhibited. The effect was gene specific, as larvae that did not molt
      in the presence of cpl or cpz dsRNA expressed the other cysteine protease, CPZ
      and CPL, respectively. This was confirmed by immunoelectron microscopy using
      antibodies directed against each enzyme. Our present study validate conclusively
      that both enzymes are essential for the molting of O. volvulus L3 to fourth-stage
      larvae. We also confirmed that the activity of the enzymes is specific to the
      changes that occur during the molting process on days 1-3, when the separation
      between the cuticles is in progress. The development of RNAi in O. volvulus L3
      could further help study many of the abundant L3 and molting L3 genes identified
      through the filarial genome project, many of which, although have no attributed
      function, were identified as vaccine candidates or potential drug targets.

PMID- 15555729
TI  - The Schistosoma mansoni Src kinase TK3 is expressed in the gonads and likely
      involved in cytoskeletal organization.
AB  - Cytoplasmic protein tyrosine kinases of the Src family play a pivotal role in the
      regulation of cellular processes including proliferation and differentiation.
      Among other functions, Src kinases are involved in regulating the cell
      architecture. In an approach to identify protein tyrosine kinases from the
      medically important parasite Schistosoma mansoni, we isolated the TK3 gene by
      degenerate primer PCR and cDNA library screening. Sequencing of the complete cDNA
      and data-base analyses indicated that TK3 is a Src family kinase. Its predicted
      size of 71 kDa was confirmed by Western blot analysis. Southern blot analysis
      showed that TK3 is a single-copy gene, and Northern blot and RT-PCR experiments
      indicated its expression in both sexes and throughout development. Localization
      studies by in situ hybridization and immunolocalization revealed that TK3 is
      predominantly expressed in the reproductive organs such as the testes of the male
      and the ovary as well as the vitellarium of the female. Its enzymatic activity
      was confirmed by functional analyses. In transient transfection experiments with
      HEK293 cells, TK3 phosphorylated the well-known Src-kinase substrate p130 Cas, an
      intracellular scaffolding protein. Yeast two-hybrid screenings in a heterologous
      invertebrate system identified dAbi, vinculin and tubulin as binding partners,
      representing molecules that fulfill functions in the cell architecture of many
      organisms. These findings suggest that TK3 may play a role in signal transduction
      pathways organizing the cytoskeleton in the gonads of schistosomes.

PMID- 15555730
TI  - DNA microarrays for comparative genomics and analysis of gene expression in
      Trypanosoma cruzi.
AB  - Trypanosoma cruzi presents high genetic diversity and parasite isolates show
      remarkable differences in biological parameters. In this study, we evaluated
      whether DNA microarrays containing CL Brener cDNAs can be used for comparative
      genomics and for the analysis of gene expression in T. cruzi. We constructed a
      prototype microarray with 710 expression sequence tags of CL Brener and 20
      sequences of T. cruzi strains. These probes represent 665 unique genes. Results
      from four hybridisations with genomic DNA of Silvio (T. cruzi I) and CL Brener
      (hybrid genotype) identified 9.3% of the probes (68/730) differentially
      represented in the two genomes. Data from eight hybridisations with cDNA obtained
      from three independent parasite harvests of Silvio and CL Brener disclosed 84
      sequences of 730 (11.5%) that showed statistical significant (P < or = 0.01)
      changes in expression (1.6-6.5-fold). Some of the array-identified sequences were
      confirmed by Southern and Northern blot analysis. Only 20% of the probes with
      increased expression in Silvio or CL Brener presented higher hybridisation with
      genomic DNA of either strain. Approximately 2.5% (18/730) and 9.0% (65/730) of
      the probes were differentially expressed (P < or = 0.01), respectively, in
      epimastigotes and metacyclic trypomastigotes of two T. cruzi II strains isolated
      from chronic chagasic patients. Microarrays identified several sequences for
      which differences in gene copy number and/or in the levels of RNA transcripts
      were previously demonstrated by different approaches. The data indicate that DNA
      microarrays are a useful tool for comparative studies between strains and provide
      further evidence for a high level of post-transcriptional regulation of RNA
      abundance in T. cruzi.

PMID- 15555731
TI  - Molecular characterization of peroxiredoxin from Entamoeba moshkovskii and a
      comparison with Entamoeba histolytica.
AB  - Peroxiredoxin of the pathogenic parasite, Entamoeba histolytica, is thought to be
      involved in protection from oxidative attack by host phagocytic cells and
      endogenously generated hydrogen peroxide. In this study, we cloned peroxiredoxin
      genes from the nonpathogenic ameba, Entamoeba moshkovskii, and characterized the
      peroxiredoxin protein. The open reading frame of three cloned cDNAs was
      demonstrated to encode a polypeptide of 218 or 217 amino acids. Identity of the
      amino acid sequence of peroxiredoxins between E. moshkovskii and E. histolytica
      was considerably high (77-81%), but the N-terminus portion of E. moshkovskii
      peroxiredoxin was shorter than that of E. histolytica. A recombinant
      peroxiredoxin of E. moshkovskii expressed in Escherichia coli exhibited hydrogen
      peroxidase activity. Its K(m) and V(max) values of 35 microM and 0.07
      micromol/min/mg protein were approximately 1 and 1.5 times greater than E.
      histolytica peroxiredoxin, respectively. In addition, the protective effect of E.
      moshkovskii peroxiredoxin against oxidative-nicking of supercoiled plasmid DNA
      was shown to be greater than that of E. histolytica peroxiredoxin. Confocal laser
      scanning microscopy, using polyclonal antibody against the recombinant E.
      moshkovskii peroxiredoxin, demonstrated that this protein was localized in the
      nucleus and cytoplasm of trophozoites, supporting its function as a protectant
      against DNA damage. Southern blot and real-time reverse transcription PCR
      analyses of the E. moshkovskii peroxiredoxin gene demonstrated that it was a
      multi-copy gene and its expression was comparable to that of E. histolytica.
      These results suggest that the antioxidant peroxiredoxin is important for
      protection against endogenously generated hydrogen peroxide in the nonpathogenic
      ameba.

PMID- 15555732
TI  - Histone acetyltransferases and deacetylase in Entamoeba histolytica.
AB  - In our efforts to understand how transcription may be regulated in Entamoeba
      histolytica, we have examined if this parasite has conserved enzymatic mechanisms
      for targeted acetylation and deacetylation of histones. Western blotting
      indicated that basic nuclear proteins in the size range of 16-23 kDa were
      acetylated in amebic trophozoites, suggesting histone acetylation. Single
      representatives of the GNAT and MYST family of histone acetyltransferases (HATs)
      were identified in the E. histolytica genome and their expression in amebic
      trophozoites was detected by reverse transcription of RNA followed by the
      polymerase chain reaction (RT-PCR). Full-length recombinant EhMYST protein
      demonstrated HAT activity with calf thymus histones and showed a preference for
      histone H4, similar to the yeast MYST protein, Esa1. However, ehMYST did not
      complement a yeast esa1 mutation. Histone deacetylase (HDAC) activity was
      detected in nuclear extracts from E. histolytica, and characteristically, was
      inhibited by trichostatin A (TSA). Consistent with the observation of HDAC
      activity, RT-PCR analysis demonstrated that an amebic hdac1 homolog (ehHDAC) is
      expressed and appropriately spliced in E. histolytica trophozoites. Our results
      suggest that mechanisms for histone acetylation and deacetylation are operational
      in E. histolytica.

PMID- 15555733
TI  - The beta-N-acetylhexosaminidase of Entamoeba histolytica is composed of two
      homologous chains and has been localized to cytoplasmic granules.
AB  - We have purified a beta-N-acetylhexosaminidase from trophozoites of Entamoeba
      histolytica to homogeneity. In SDS-PAGE, the enzyme yielded a single protein band
      at an apparent M(r) of 64,000. The elution behaviour of the native enzyme upon
      molecular sieve chromatography corresponded to a molecular mass of approximately
      132,000 suggesting that the enzyme is a dimer. Upon sedimentation velocity
      centrifugation, hexosaminidase activity sedimented at 12S, implying aggregation
      to a higher molecular mass complex with an apparent M(r) of approximately
      400,000. Based on the N-terminal sequence of the purified enzyme and on data
      extracted from the E. histolytica genomic data base, we amplified and cloned two
      genes (EhHEXA and EhHEXB) coding for two presumptive, highly similar
      hexosaminidase chains which we designated as Ehhexalpha and Ehhexbeta. Northern
      blot analysis indicated that the two genes were expressed to a similar level, and
      Western blotting with chain-specific antisera showed that the trophozoites
      synthesize both proteins. By cell fractionation, the hexosaminidase was found to
      be a major component of cytoplasmic granules; these contain tissue-destructive
      factors and are released after collagen-induced exocytosis to the cell surface.
      In agreement with this observation, immunocytochemistry with an antiserum cross
      reacting with both hexosaminidase chains revealed strong fluorescence in surface
      patches, which we interpret as released granules, and in vesicles throughout the
      cell. Its localization in cytoplasmic granules strengthens the notion that the
      hexosaminidase complex may contribute to amoebic pathogenicity.

PMID- 15555734
TI  - Cytological and biochemical evidence for a gonad-preferential interplay of
      SmFKBP12 and SmTbetaR-I in Schistosoma mansoni.
AB  - In eukaryotes, FK506-binding proteins with a molecular weight of 12 kDa (FKBP12s)
      influence a variety of signal transduction pathways that regulate cell division,
      differentiation, and ion homeostasis. Amongst these, TGFbeta signaling and
      calcineurin (CN) phosphatase activity is modulated by FKBP12 via binding to
      TGFbeta-family type I receptors (TbetaR-Is) or to the CN subunit A, respectively.
      In this work, we demonstrate the tissue-specific expression of the Schistosoma
      mansoni FKBP12 homologue (SmFKBP12) in the gonads of female parasites as well as
      in the tegument of both genders. Components of the TGFbeta pathway have been
      characterized in schistosomes and their roles in mediating host-parasite or male
      female interactions proposed. We show that a schistosome TGFbeta-family type I
      receptor (SmTbetaR-I, SmRK-1) is expressed in the female gonads, suggesting that
      SmFKBP12 may regulate its activity in this tissue. This hypothesis is supported
      by yeast two-hybrid analyses showing a direct binding of SmFKBP12 and SmTbetaR-I,
      which was specifically inhibited by the drug FK506. Our data provide the first
      evidence for the activity of a transmembrane receptor in the vitellarium of
      schistosome females and indicate that FKBP12-meditated regulation of the TGFbeta
      pathway is evolutionarily conserved in a primitive metazoan such as Schistosoma.
      Furthermore, we show that the schistosome CN (SmCN) is not expressed in the
      female gonads, but co-localizes with SmFKBP12 only in the tegument. From these
      data we conclude an SmFKBP12/SmTbetaR-I, but not an SmCN/SmFKBP12 interplay in
      the female gonads.

PMID- 15555735
TI  - Identification and characterisation of RAMA homologues in rodent, simian and
      human malaria species.

PMID- 15555736
TI  - Conservation and divergence in erythrocyte invasion ligands: Plasmodium
      reichenowi EBL genes.

PMID- 15555738
TI  - Treatment targets in inflammatory bowel disease.

PMID- 15555739
TI  - Regulation of intestinal epithelial function: a link between opportunities for
      macromolecular drug delivery and inflammatory bowel disease.
AB  - The intestinal epithelium performs a multitude of tasks related to digestion and
      homeostasis. As a consequence of ingestion, this tissue must also participate in
      activities associated with protecting the body from potential pathogenic agents
      and toxic materials. To efficiently perform tasks associated with digestion and
      these protective functions, the intestinal epithelium has established several
      anatomical, biochemical and physiological barriers to impede unregulated uptake
      of materials. In order to perform functions of digestion and homeostasis, the
      intestinal epithelium uses mechanisms that allow dynamic modulation of regulated
      uptake pathways that can respond rapidly to changes in diet, health and
      challenges from pathogenic agents and macromolecules. This review focuses on
      specific, recent advances made in understanding cellular pathways and mechanisms
      that regulate dynamic processes of these barriers and examines the feasibility of
      drug delivery strategies focusing on macromolecular therapeutics potentially
      useful in the treatment of inflammatory bowel disease (IBD).

PMID- 15555740
TI  - Are there predictors of Remicade treatment success or failure?
AB  - Infliximab (Remicade) is an antitumor necrosis factor (TNF) therapy effective in
      both induction and maintenance of remission in Crohn's disease. Identifying
      predictors of response or relapse to infliximab is important given the potential
      toxicities and cost of this therapy. Currently available data suggest that
      concurrent immunosuppressant therapy, certain clinical characteristics,
      biological and immunological markers, and gene polymorphism may correlate with
      response to infliximab. However, no single variable has been consistently shown
      or definitely proven in studies to be a predictor of response to infliximab to be
      of practical value in current clinical practice. Data from the literature in
      these areas are reviewed in this article, pointing to the need for additional
      research in this topic.

PMID- 15555741
TI  - New oral delivery systems for treatment of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is often localized to specific sites in the
      gastrointestinal tract (GIT). As a result, this disease can be treated with oral
      site-specific (targeted) drug delivery systems. Targeted delivery systems for
      treatment of IBD are designed to increase local tissue concentrations of
      antiinflammatory drugs from lower doses compared with systemic administration.
      This review addresses the impact disease has or may have on oral targeted
      delivery for treatment of IBD as well as a number of delivery approaches
      currently used in marketed products or under investigation. Delivery systems
      reviewed rely on temporal control, changes in pH along the GIT, the action of
      local enzymes to trigger drug release, and changes in intraluminal pressure.
      Dissolution of enteric polymer coatings due to a change in local pH and reduction
      of azo-bonds to release an active agent are both used in commercially marketed
      products. Newer approaches showing promise in treating IBD are based on
      polysaccharides. These materials are most effective when used as compression
      coatings around core tablets, which contain the active agent. More complex
      polymeric prodrugs systems are also under investigation. If the dose of the drug
      is sufficiently low, this approach may also prove useful in improving treatment
      of IBD.

PMID- 15555742
TI  - Topical delivery of therapeutic agents in the treatment of inflammatory bowel
      disease.
AB  - For targeting local and systemic inflammatory processes in inflammatory bowel
      disease (IBD) therapeutic agents of first choice (e.g. aminosalicylates,
      corticosteroids) have been developed in special galenic forms to accomplish the
      topical delivery of the active compounds to the terminal ileum (Crohn's disease)
      and/or the colon (Crohn's disease and ulcerative colitis). However, it has to be
      realized that intestinal physiology (e.g. motility, intraluminal pH profiles),
      extent and pattern of IBD as well as drug disposition demonstrate large
      interindividual differences resulting in variable clinical response rates between
      about 35% and 75%. 5-Aminosalicylate (5-AS) can be delivered to the colon either
      by azo-prodrugs (e.g. sulfasalazine, olsalazine or balsalazide) or by direct
      rectal administration of 5-AS in form of enemas, foam or suppositories. Such
      formulations will be only effective in patients with ulcerative colitis (UC).
      Various slow/controlled release preparations of 5-AS have been developed for oral
      use. Some of them (e.g. Pentasa, Salofalk) release sufficient 5-AS already in the
      small bowel which could provide some additional benefit in Crohn's disease (CD).
      As urinary and faecal recoveries of total 5-AS are similar for all oral
      formulations, no major clinical differences can be expected. Extent of the
      disease, profile of adverse effects and patient's acceptance provide some
      guidance for selection of the particular agent. Rectal installation of several
      glucocorticosteroids has been employed for many years. More recently scientific
      and clinical interest has been focused on budesonide which is extensively
      presystemically metabolized in the intestinal wall and the liver. Therefore, its
      systemic availability is low (10-15%) independent whether budesonide is
      administered orally as controlled release formulation in patients with CD or
      rectally as enema in patients with UC. Numerous pharmacokinetic and clinical
      studies have documented the anticipated topical delivery and clinical efficacy of
      this corticosteroid without serious side effects such as cushingoid features. It
      can be assumed that for any novel therapeutic principle in IBD the approach of
      topical delivery will be also tried.

PMID- 15555743
TI  - Mesalamine delivery systems: do they really make much difference?
AB  - Sulfasalazine's role as the first-line of therapy in patients with inflammatory
      bowel disease has led to the development of other "designer" aminosalicylates,
      which eliminate the sulfa-moiety, and attempt to target the topically active
      mesalamine to the inflamed bowel. Olsalazine sodium and balsalazide disodium
      utilize the same azo-bond structure as sulfasalazine, requiring release of active
      mesalamine by colonic bacteria, and thus targeting these agents to the colon.
      Other mesalamine delivery systems use pH-dependant- or moisture-release to
      liberate the active mesalamine in both the large and small bowel. Direct
      application of mesalamine via enema or suppository is also effective in patients
      with distal colitis. The pharmacology and thus the undesirable drug absorption
      rates differ between drugs, although the clinical importance of these
      characteristics is debatable. Differences in release-systems, the impact of the
      fed and fasting state, and unique patient intolerances to individual agents
      demand an understanding of each of these products, and their application to
      patient therapy.

PMID- 15555744
TI  - Targeted delivery, safety, and efficacy of oral enteric-coated formulations of
      budesonide.
AB  - Budesonide is a potent corticosteroid with a high first-pass metabolism rate. Two
      commercially available enteric-coated pH-dependent release formulations (Entocort
      EC and Budenofalk) deliver budesonide to the ileum and proximal colon, regions
      most commonly affected in Crohn's disease. The drug's effectiveness in this
      disease has been proven in multiple, placebo-controlled trials, where it has been
      shown to be superior to mesalamine and placebo, and equivalent to prednisolone
      for the control of mild to moderately active right-sided Crohn's disease. This
      beneficial therapeutic effect comes with less adrenal suppression and a small
      improvement in the clinical adverse effect profile, as compared to prednisolone.
      However, budesonide provides no benefit over conventional therapy for left-sided
      colonic disease, and it is less effective for treatment of more severe disease
      activity and more distal colonic disease. Continuous budesonide does not prolong
      remission and is, therefore, best used in an intermittent fashion to treat acute
      exacerbations.

PMID- 15555746
TI  - Improving patient safety by examining pathology errors.
AB  - A considerable void exists in the information available regarding anatomic
      pathology diagnostic errors and their impact on clinical outcomes. To fill this
      void and improve patient safety, four institutional pathology departments
      (University of Pittsburgh, Western Pennsylvania Hospital, University of Iowa
      Hospitals and Clinics, and Henry Ford Hospital System) have proposed the
      development of a voluntary, Web-based, multi-institutional database for the
      collection and analysis of diagnostic errors. These institutions intend to use
      these data proactively to implement internal changes in pathology practice and to
      measure the effect of such changes on errors and clinical outcomes. They believe
      that the successful implementation of this project will result in the study of
      other types of diagnostic pathology error and the expansion to national
      participation. The project will involve the collection of multi-institutional
      anatomic pathology diagnostic errors in a large database that will facilitate a
      more detailed analysis of these errors, including their effect on patient
      outcomes. Participating institutions will perform root cause analysis for
      diagnostic errors and plan and execute appropriate process changes aimed at error
      reduction. The success of these interventions will be tracked through analysis of
      postintervention error data collected in the database. Based on their preliminary
      studies, these institutions proposed the following specific aims: Specific aim
      #1: To use a Web-based database to collect diagnostic errors detected by
      cytologic histologic correlation and by second-pathologist review of conference
      cases. Specific aim #2: To analyze the collected error data quantitatively and
      generate quality performance reports that are useful for institutional quality
      improvement programs. Specific aim #3: To plan and implement interventions to
      reduce errors and improve clinical outcomes, based on information derived from
      root cause analysis of diagnostic errors. Specific aim #4: To assess the success
      of implemented interventions by quantitative measure of postinterventional errors
      and clinical outcomes and by qualitative assessment by project participants.
      Funding for this project was approved by the Agency for Health Care Research and
      Quality in September 2002, and data collection and analysis are ongoing. Over
      5000 errors have been collected in the database, and the clinical outcomes of
      these errors have been tracked. At a national meeting in November 2003, root
      cause analysis was performed to determine causes of errors. The findings of these
      root cause analyses have been presented at national pathology meetings and are
      currently being published.

PMID- 15555747
TI  - Error-free pathology: applying lean production methods to anatomic pathology.
AB  - The current state of our health care system calls for dramatic changes. In their
      pathology department, the authors believe these changes may be accomplished by
      accepting the long-term commitment of applying a lean production system. The
      ideal state of zero pathology errors is one that should be pursued by
      consistently asking, "Why can't we?" The philosophy of lean production systems
      began in the manufacturing industry: "All we are doing is looking at the time
      from the moment the customer gives us an order to the point when we collect the
      cash. And we are reducing that time line by removing non-value added wastes". The
      ultimate goals in pathology and overall health care are not so different. The
      authors' intention is to provide the patient (customer) with the most accurate
      diagnostic information in a timely and efficient manner. Their lead
      histotechnologist recently summarized this philosophy: she indicated that she
      felt she could sleep better at night knowing she truly did the best job she
      could. Her chances of making an error (in cutting or labeling) were dramatically
      decreased in the one-by-one continuous flow work process compared with previous
      practices. By designing a system that enables employees to be successful in
      meeting customer demand, and by empowering the frontline staff in the development
      and problem solving processes, one can meet the challenges of eliminating waste
      and build an improved, efficient system.

PMID- 15555748
TI  - Barriers to the implementation of patient safety initiatives.
AB  - Since release of the Institute of Medicine Report "To Err is Human:Building a
      Safer Health System" in 1999, a huge effort has been expended on error-related
      clinically applied research and on the implementation of new standards and
      practices related to quality improvement and patient safety. Nonetheless,
      measurable improvements in the quality of delivered care and reductions in
      medical errors have been variable and modest in most cases. Multiple barriers to
      the implementation of patient safety and error reduction initiatives have been
      identified in the literature. The greater part of this article is devoted to
      three fundamental barriers: physicians' intolerance for uncertainty, health
      professionals' fears, and an organizational structure and culture that are
      incongruent with increasing patient safety.

PMID- 15555749
TI  - Pathology and patient safety: the critical role of pathology informatics in error
      reduction and quality initiatives.
AB  - Understanding the role of pathology informatics in patient safety entails an
      introduction to terminology and projects that have represented efforts to date in
      this area. The authors provide a short alphabetized introduction to several
      "buzzwords" and terms related to tools and processes that are used by health care
      research experts and workers involved in patient safety initiatives. The authors
      also include short descriptions of key health care research and patient safety
      projects that are relevant to pathology. They aim to highlight the areas where
      pathology informatics in all of its flavors (production systems provided by
      vendors as well as research and development efforts) can play a role in promoting
      patient safety.

PMID- 15555750
TI  - Crossing the quality chasm: a requirement for successful cervical cancer
      prevention in developing countries.
AB  - Disease prevention requires sociopolitical change, which in turn requires the
      participation of those for whom the change is intended, including demographic
      groups at high risk for disease, appropriate governmental authorities, and
      essential health care personnel. Multiparous women of lowest socioeconomic
      status, the demographic group at highest risk for the development of cervical
      cancer, lack sociopolitical leverage almost by definition. Pap screening in
      developing countries is an idea whose time has come, but it is also an ethical
      imperative currently lacking a substantial sociopolitical constituency.
      Noncytologic screening methods currently benefit from sponsorship by corporate
      manufacturers and by donor organizations such as the Bill and Melinda Gates
      Foundation. Pap screening efforts in developing countries will benefit from the
      involvement of cytology organizations based in developed countries. Future
      assessments of the progress of cervical cancer prevention efforts in developing
      countries will benefit from additional examination of the interactions between
      quality and sociopolitical obstacles to change. Many of these obstacles will be
      elucidated by following the money, as well as the science, involved in cervical
      screening activities.

PMID- 15555751
TI  - Detecting and preventing the occurrence of errors in the practices of laboratory
      medicine and anatomic pathology: 15 years' experience with the College of
      American Pathologists' Q-PROBES and Q-TRACKS programs.
AB  - This review extracts those studies from the CAP Q-PROBES and Q-TRACKS programs
      that have benchmarked and monitored the occurrence of errors in the practices of
      laboratory medicine and anatomic pathology. The outcomes of these studies
      represent in aggregate the analysis of millions of data points collected in
      thousands of hospitals throughout the United States. Also presented in this
      review are hospital and laboratory practices associated with improved performance
      (ie, fewer errors). Only those associations that were shown to be statistically
      significant are presented. They represent only a small fraction of the practices
      examined in these studies. The reader is encouraged to peruse the Q-PROBES
      studies cited in the reference list to learn about the wide range of practices
      investigated. The institution of some of these practices for which the associated
      error reductions were not statistically significant might nonetheless improve
      performance in some environments. There is no way of knowing whether some better
      performing institutions compensated for not employing presumably beneficial
      practices by applying other practices about which the studies' authors neglected
      to inquire. Nor is there any way of knowing whether institutions in which
      performance was poor employed presumably beneficial practices, but possessed
      operational flaws about which the studies' authors neglected to inquire.
      Certainly, hospitals operating in the bottom 10% of benchmarked performances
      would do well to investigate the possibility that some of these practices might
      reduce the incidence of errors in their institutions. From the results of these
      studies, there emerge two complementary strategies that appear to be associated
      with reduction of errors. Obviously, the first strategy involves doing what is
      necessary to prevent the occurrence of errors in the first place. Several tactics
      may accomplish this goal. Healthcare workers responsible for specific tasks must
      be properly educated and motivated to perform those tasks with as few errors as
      possible. There must be written policies and protocols detailing responsibilities
      and providing contingencies when those responsibilities are not met. The
      successful completion of required tasks must be documented, especially those
      tasks that are performed as requisite to others. In other words, it should be
      impossible to move on to subsequent operations in testing processes before
      documenting the successful completion of previous requisite operations. Finally,
      the opportunities for making errors must be reduced. Specifically, the number of
      steps in which specimens are delivered to laboratories, tests are performed, and
      results are disseminated to those who use them must be reduced as much as
      possible. The second strategy involves the assumption that despite our best
      efforts to prevent them, errors will occur. No matter how smart we are, no matter
      how careful we try to be, we will make mistakes. It is essential that systems
      designed to eliminate errors include elements of redundancy to catch those
      mistakes. Work must be checked and verified before therapeutic decisions are
      finalized. This is especially true when those decisions are irrevocable and the
      potential damage caused by errors cannot be undone. Ideally, systems that use
      redundancy should include provisions to shut down the testing process altogether
      when the successful execution of previous steps cannot be verified. Once error
      detection systems are established, service providers can gauge their performance
      by employing tools of continuous monitoring to assess the degree to which health
      care workers comply with required procedures, and with which services achieve
      their intended outcomes.

PMID- 15555752
TI  - Identification errors in pathology and laboratory medicine.
AB  - Identification errors involve misidentification of a patient or a specimen.
      Either has the potential to cause patients harm. Identification errors can occur
      during any part of the test cycle; however, most occur in the preanalytic phase.
      Patient identification errors in transfusion medicine occur in 0.05% of
      specimens; for general laboratory specimens the rate is much higher, around 1%.
      Anatomic pathology, which involves multiple specimen transfers and hand-offs, may
      have the highest identification error rate. Certain unavoidable cognitive
      failures lead to identification errors. Technology, ranging from bar-coded
      specimen labels to radio frequency identification tags, can be incorporated into
      protective systems that have the potential to detect and correct human error and
      reduce the frequency with which patients and specimens are misidentified.

PMID- 15555753
TI  - Patient safety in point-of-care testing.
AB  - In the authors' view, the following four points compose the current state of the
      question of patient safety in point-of-care testing: The collision of definitions
      used in this article with actual practice in point-of-care testing is evidence
      for the likelihood of error in this genre of clinical tests. Uncovering of latent
      conditions conducive to error is the objective for investigations of this
      likelihood. A modified Kost classification serves as a basis for determining
      where latent conditions appear in the point-of-care testing process and as a
      framework in which to recognize these errors in an error classification process.
      Errors in point-of-care testing are likely to arise most frequently in the steps
      of patient identification, specimen collection, and result reporting. In the
      absence of an adequate evidence base, the authors recommend as measures to build
      a culture of patient safety in point-of-care testing the components of the
      standard model of safe laboratory testing. This model inculcates the laboratory
      ethos of test operator competence, procedure adherence, quality control, and
      result integrity. These objectives can be achieved by integrating operator
      training, program supervision, competence assessment, and proficiency
      demonstration into an institution's or practice's point-of-care testing program.
      Based on the authors' hypothesis that medical errors in point-of-care testing,
      which lead to preventable adverse events most often arise in three testing
      processes--patient identification, specimen collation, and result reporting--they
      recommend ongoing monitors of these critical steps. If they are wrong, such
      monitoring will disprove their hypothesis; if they are right, it will measurably
      reduce medical error in point-of-care testing.

PMID- 15555754
TI  - The laboratory is a key partner in assuring patient safety.
AB  - Medical errors have a great impact on patient outcomes. They can cause serious
      injury to patients or even result in their deaths. However, morbidity and
      mortality can sometimes be prevented by the timely and effective action of health
      care workers. Several IOM Reports have focused on the problem of errors in the
      United States health care system and identified gaps that need to be addressed.
      As part of the overall health care system, clinical laboratories are vulnerable
      to medical errors. Because of significant efforts on the part of both the
      laboratories and the manufacturers of laboratory equipment and reagents, the
      errors in the analytic phase of the total testing process now represent the
      smallest portion of testing errors. Currently, laboratory testing errors occur
      most frequently in the preanalytic phase. The primary reason for the high
      prevalence of preanalytic errors is that, at the present time, it is difficult to
      monitor all preanalytic variables and to implement necessary improvement
      processes, particularly when some of the variables (like phlebotomy) are not
      under the control of the laboratory. Considerable efforts have been made by
      laboratory professionals and other stakeholders to decrease testing errors.
      Minimal quality requirements have been set through regulations for both
      laboratory testing and the manufacture of medical equipment and reagents. At the
      same time, nonregulatory approaches have greatly affected the quality of
      laboratory testing. These include laboratory standards, various quality
      improvement programs, voluntary reporting of adverse events, and, in the near
      future, the National Report on the Quality of Laboratory Services. The
      introduction of successful approaches from other industries, such as Six Sigma
      and Lean, also will help reduce the rate of laboratory errors. The clinical
      laboratory has done more than most other sectors of health care to decrease the
      occurrence of medical errors, making it a key partner inpatient safety.

PMID- 15555755
TI  - Computational models of epileptiform activity in single neurons.
AB  - A series of original computational models written in NEURON of increasing
      physiological and morphological complexity were developed to determine the
      dominant causes of epileptiform behavior. Current injections to a model
      hippocampal pyramidal neuron consisting of three compartments produced the
      sustained depolarizations (SD) and simple paroxysmal depolarizing shifts (PDS)
      characteristic of ictal and interictal behavior in a cell, respectively. Our
      results indicate that SDs are the result of the semi-saturation of Na+, Ca2+ and
      K+ active channels, particularly the CaN, with regular Na+/K+ spikes riding atop
      a saturated depolarization; PDS rides on a similar semi-saturated depolarization
      whose shape depends more heavily on interactions between low-threshold voltage
      gated Ca2+ channels (CaT) and Ca(2+)-dependent K+ channels. Our results reflect
      and predict recent physiological data, and we report here a cellular basis of
      epilepsy whose mechanisms reside mainly in the membrane channels, and not in
      specific morphology or network interactions, advancing a possible resolution to
      the cellular/network debate over the etiology of epileptiform activity.

PMID- 15555756
TI  - Analysis of two-component signal transduction by mathematical modeling using the
      KdpD/KdpE system of Escherichia coli.
AB  - A mathematical model for the KdpD/KdpE two-component system is presented and its
      dynamical behavior is analyzed. KdpD and KdpE regulate expression of the kdpFABC
      operon encoding the high affinity K+ uptake system KdpFABC of Escherichia coli.
      The model is validated in a two step procedure: (i) the elements of the signal
      transduction part are reconstructed in vitro. Experiments with the purified
      sensor kinase and response regulator in presence or absence of DNA fragments
      comprising the response regulator binding-site are performed. (ii) The mRNA and
      molecule number of KdpFABC are determined in vivo at various extracellular K+
      concentrations. Based on the identified parameters for the in vitro system it is
      shown, that different time hierarchies appear which are used for model reduction.
      Then the model is transformed in such a way that a singular perturbation problem
      is formulated. The analysis of the in vivo system shows that the model can be
      separated into two parts (submodels which are called functional units) that are
      connected only in a unidirectional way. Hereby one submodel represents signal
      transduction while the second submodel describes the gene expression.

PMID- 15555757
TI  - Solving traveling salesman problems with DNA molecules encoding numerical values.
AB  - We introduce a DNA encoding method to represent numerical values and a biased
      molecular algorithm based on the thermodynamic properties of DNA. DNA strands are
      designed to encode real values by variation of their melting temperatures. The
      thermodynamic properties of DNA are used for effective local search of optimal
      solutions using biochemical techniques, such as denaturation temperature gradient
      polymerase chain reaction and temperature gradient gel electrophoresis. The
      proposed method was successfully applied to the traveling salesman problem, an
      instance of optimization problems on weighted graphs. This work extends the
      capability of DNA computing to solving numerical optimization problems, which is
      contrasted with other DNA computing methods focusing on logical problem solving.

PMID- 15555758
TI  - Metabolic pathway analysis of enzyme-deficient human red blood cells.
AB  - Five enzymopathies (G6PDH, TPI, PGI, DPGM and PGK deficiencies) in the human red
      blood cells are investigated using a stoichiometric modeling approach, i.e.,
      metabolic pathway analysis. Elementary flux modes (EFMs) corresponding to each
      enzyme deficiency case are analyzed in terms of functional capabilities. When
      available, experimental findings reported in literature related to metabolic
      behavior of the human red blood cells are compared with the results of EFM
      analysis. Control-effective flux (CEF) calculation, a novel approach which allows
      quantification and interpretation of determined EFMs, is performed for further
      analysis of enzymopathies. Glutathione reductase reaction is found to be the most
      effective reaction in terms of its CEF value in all enzymopathies in parallel
      with its known essential role for red blood cells. Efficiency profiles of the
      enzymatic reactions upon the degree of enzyme deficiency are obtained by the help
      of the CEF approach, as a basis for future experimental studies. CEF analysis,
      which is found to be promising in the analysis of erythrocyte enzymopathies, has
      the potential to be used in modeling efforts of human metabolism.

PMID- 15555759
TI  - Does quantum mechanics play a non-trivial role in life?
AB  - There have been many claims that quantum mechanics plays a key role in the origin
      and/or operation of biological organisms, beyond merely providing the basis for
      the shapes and sizes of biological molecules and their chemical affinities. These
      range from Schrodinger's suggestion that quantum fluctuations produce mutations,
      to Hameroff and Penrose's conjecture that quantum coherence in microtubules is
      linked to consciousness. I review some of these claims in this paper, and discuss
      the serious problem of decoherence. I advance some further conjectures about
      quantum information processing in bio-systems. Some possible experiments are
      suggested.

PMID- 15555760
TI  - Event detection by forward- and backward-prediction, illustrating the analysis
      for behaviors of black larder beetle Dermestes haemorrhoidalis Kuster.
AB  - There are several studies that estimate the emergent event from the time series
      of behavior in some organisms. However, they do not focus on the emergent event
      itself. Our aim is to detect the emergent event from the time series of
      individual's behavior, focusing on the transition from predictable machinery
      behavior to purpose-oriented behavior and vice versa. We recorded the behavior of
      larvae and adults of black larder beetle. To detect the emergent event of the
      beetle, we defined a forward- and backward-prediction model. In the forward
      prediction, the next state in the time series of behavior was interpreted by
      precedent behavior. In the backward-prediction, the previous state in the time
      series of behavior was interpreted by subsequent behavior. The time step with
      conspicuous peak of the co-intensity of errors in the forward- and backward
      prediction was regarded as the timing at which the emergent event occurs. At the
      same time, the time series of states was estimated to determine whether noise was
      stationary or non-stationary. The attribute of noise was estimated using the
      Allan variance. The time series of the larvae's velocity of walking showed
      stationary noise. But in the case of the adults, whole time series contained 1/f
      noise. And, when time series was divided before and after the detected event, the
      noise changed from stationary to non-stationary and vice versa. These results
      suggest that development enables an individual to change the internal mechanism
      of walk considering the slight change of environment.

PMID- 15555761
TI  - A one locus, biased mutation model and its equivalence to an unbiased model.
AB  - Experimental data suggests that for some continuously-varying characters under
      stabilising selection, mutation may cause a mean change in the value of the
      character. A one locus, mathematical model of a continuously-varying biological
      character with this property of biased mutation is investigated. Via a
      mathematical transformation, the equilibrium equation describing a large
      population of individuals is reduced to the equilibrium equation describing a
      mutationally unbiased problem. Knowledge of an unbiased problem is thus
      sufficient to determine all equilibrium properties of the corresponding biased
      problem. In the biased mutation problem, the dependence of the mean equilibrium
      value of the character, as a function of the mutational bias, is non-monotonic
      and remains small, for all levels of mutational bias. The analysis presented in
      this work sheds new light on Turelli's House of Cards Approximation.

PMID- 15555762
TI  - Memetic algorithms for the unconstrained binary quadratic programming problem.
AB  - This paper presents a memetic algorithm, a highly effective evolutionary
      algorithm incorporating local search for solving the unconstrained binary
      quadratic programming problem (BQP). To justify the approach, a fitness landscape
      analysis is conducted experimentally for several instances of the BQP. The
      results of the analysis show that recombination-based variation operators are
      well suited for the evolutionary algorithms with local search. Therefore, the
      proposed approach includes--besides a highly effective randomized k-opt local
      search--a new variation operator that has been tailored specially for the
      application in the hybrid evolutionary framework. The operator is called
      innovative variation and is fundamentally different from traditional crossover
      operators, since new genetic material is included in the offspring which is not
      contained in one of the parents. The evolutionary heuristic is tested on 35
      publicly available BQP instances, and it is shown experimentally that the
      algorithm is capable of finding best-known solutions to large BQPs in a short
      time and with a high frequency. In comparison to other approaches for the BQP,
      the approach appears to be much more effective, particularly for large instances
      of 1000 or 2500 binary variables.

PMID- 15555763
TI  - Evolutionary dynamics of cellular automata-based self-replicators in hostile
      environments.
AB  - In this paper we investigate population dynamics, genealogy and complexity
      increase of locally interacting populations of cellular automata-based evolving
      self-replicating loops (evoloops). We outline experiments indicating that the
      evolutionary growth in complexity, known to be achievable in principle given the
      complete genetic accessibility granted by universal construction, may be
      achievable in practice using much simpler replicating structures. By introducing
      evoloop populations to hostile environments, we demonstrate that selection
      pressures toward smaller species can be mediated to enable evolutionary
      accessibility to larger species, which themselves roam a much more vast portion
      of genetic state-space. We show that this growth in size results from
      intrinsically biased genealogy inherent in the rules of the evoloop CA, normally
      suppressed by selection pressures from direct competition favouring the smallest
      species. This shows that, in populations of simple self-replicating structures, a
      limited form of complexity-increase may result from a process which is driven by
      biased genealogical connectivity--a purely emergent property arising out of
      bottom-up evolutionary dynamics--and not just by adaptation . Implications of
      this result are discussed and contrasted with other self-replication studies in
      Artificial Life and Biology.

PMID- 15555764
TI  - A particle swarm optimizer with passive congregation.
AB  - This paper presents a particle swarm optimizer (PSO) with passive congregation to
      improve the performance of standard PSO (SPSO). Passive congregation is an
      important biological force preserving swarm integrity. By introducing passive
      congregation to PSO, information can be transferred among individuals of the
      swarm. A particle swarm optimizer with passive congregation (PSOPC) is tested
      with a set of 10 benchmark functions with 30 dimensions and compared to a global
      version of SPSO (GSPSO), a local version of SPSO (LSPSO), and PSO with a
      constriction factor (CPSO), respectively. Experimental results indicate that the
      PSO with passive congregation improves the search performance on the benchmark
      functions significantly.

PMID- 15555765
TI  - Significance of kinetic degrees of freedom in operation of the actomyosin motor.
AB  - The actomyosin motor as a principal functional component of cell motility is
      highly coordinated in regulating the participating molecular components. At the
      same time, it has to be flexible and plastic enough to accommodate itself to a
      wide variety of operational conditions. We prepared two different types of
      actomyosin systems. One is a natural intact actomyosin system with no artificial
      constraint on the kinetic degrees of freedom of the actin filaments, and the
      other is a regulated one with actin filaments supplemented by intra- and
      intermolecular crosslinking to suppress the kinetic degrees of freedom to a
      certain extent. Crosslinked actomyosin systems were found to remain almost
      insensitive to calcium regulation even when intact troponin-tropomyosin
      regulatory component was incorporated. Both the ATPase and the motile activities
      of the actin filaments sliding on myosin molecules were markedly lowered by the
      crosslinking. In contrast, once the crosslinking was cleaved, both properties
      returned to the normal as with intact actomyosin systems.

PMID- 15555766
TI  - Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a disorder without a molecular marker in peripheral
      tissues or a disease modifying treatment. As increasing evidence has suggested a
      role for glycogen synthase kinase-3 (GSK-3) in the pathogenesis of the condition
      we measured total GSK-3 protein (alpha and beta isoforms) and GSK-3 activity
      (serine 9 phosphorylation) in a group of healthy elderly people, in AD and in
      mild cognitive impairment (MCI). Total GSK-3 protein was increased in both AD and
      in MCI without a compensatory decrease in activity. These data suggest that GSK-3
      assays might be a useful diagnostic marker in a readily available tissue and
      moreover that GSK-3 activity is increased in the prodromal phase of the disorder
      suggesting that inhibition of GSK-3 might be a useful therapeutic strategy.

PMID- 15555767
TI  - Neural activity associated with metaphor comprehension: spatial analysis.
AB  - Though neuropsychological data indicate that the right hemisphere (RH) plays a
      major role in metaphor processing, other studies suggest that, at least during
      some phases of this processing, a RH advantage may not exist. The present study
      explores, through a temporally agile neural signal--the event-related potentials
      (ERPs)--, and through source-localization algorithms applied to ERP recordings,
      whether the crucial phase of metaphor comprehension presents or not a RH
      advantage. Participants (n=24) were submitted to a S1-S2 experimental paradigm.
      S1 consisted of visually presented metaphoric sentences (e.g., "Green lung of the
      city"), followed by S2, which consisted of words that could (i.e., "Park") or
      could not (i.e., "Semaphore") be defined by S1. ERPs elicited by S2 were analyzed
      using temporal principal component analysis (tPCA) and source-localization
      algorithms. These analyses revealed that metaphorically related S2 words showed
      significantly higher N400 amplitudes than non-related S2 words. Source
      localization algorithms showed differential activity between the two S2
      conditions in the right middle/superior temporal areas. These results support the
      existence of an important RH contribution to (at least) one phase of metaphor
      processing and, furthermore, implicate the temporal cortex with respect to that
      contribution.

PMID- 15555768
TI  - Time course of GABA in the synaptic clefts of inhibitory synapses in the rostral
      nucleus of the solitary tract.
AB  - Concentration and time course of neurotransmitter in the synaptic cleft
      determines the amplitude and the duration of the resulting postsynaptic current.
      However, technical limitations involved in monitoring the time course of
      neurotransmitter concentration in the extra-cellular space have prevented direct
      evaluation of factors that influence neurotransmitter level in the cleft. Tetanic
      stimulation results in saturation of postsynaptic GABA(A) receptors in the
      rostral nucleus of the solitary tract (rNST) and GABA diffusion defines the decay
      time course of the inhibitory potentials or currents (IPSP/Cs). By applying a
      GABA concentration-response curve to these data it is possible to calculate the
      GABA concentration transient in the clefts of rNST inhibitory synapses. The
      analysis indicates that tetanic stimulation produces a GABA concentration that
      exceeds the concentration of neurotransmitter required to activate all
      postsynaptic GABA(A) receptors, resulting in short-term modification of the
      IPSP/Cs decay time. Moreover, the results also demonstrate that the rate of
      diffusion of GABA from the synaptic cleft is defined by two exponentials. A
      mathematical model of this process has been developed that supports these
      conclusions.

PMID- 15555769
TI  - White matter injury in the immature brain: role of interleukin-18.
AB  - Inflammation is likely to be important in the pathophysiology of white matter
      damage in the immature brain. In order to investigate the involvement of
      interleukin (IL)-18, we subjected 9-day-old IL-18-deficient and wild-type (WT)
      mice to hypoxia-ischemia (HI) (unilateral carotid ligation and exposure to 10%
      oxygen) and white matter injury was evaluated after 3 days by immunostaining for
      myelin basic protein (MBP) and neurofilament (NF). The immunoreactivity of MBP
      was significantly higher by 92, 49 and 21%, respectively, in subcortical white
      matter, striatum and thalamus in IL-18-deficient mice versus WT mice following
      HI. Similarly, there was a more pronounced immunoreactivity of NF by 78% in the
      subcortical white matter in IL-18 KO versus WT mice. IL-18 was expressed by
      astrocytes and microglia, whereas the IL-18 receptor was mainly found in
      astrocytes localized in and around the subventricular white matter. Taken
      together, these results indicate that release of IL-18 may play an important role
      in the development of white matter injury in the neonatal brain.

PMID- 15555770
TI  - Problem size effect in additions and subtractions: an event-related potential
      study.
AB  - The psychophysiological basis of problem size effect in the arithmetical
      processing of additions and subtractions was studied with event-related brain
      potentials (ERP). Subjects were presented sequences of seven numbers, and ERPs
      elicited to the sixth number were analyzed. Two variables were manipulated:
      operation type (addition and subtraction) and problem size (by adding or
      subtracting 2, 3 or 4). Results showed two phases in the ERP pattern: an early
      phase, appearing to reflect automatic processing involved in stimulus
      identification, and a positive slow wave, believed to be a computing indicator of
      the subsequent calculation. The amplitude of this positive slow wave was
      modulated by the problem size (the more problem size, the larger the amplitude),
      suggesting that the amplitude of this slow wave indexes the activation of the
      cerebral network underlying problem size effect.

PMID- 15555771
TI  - Emotional deficit in subjects with psychopathic tendencies as assessed by the
      Minnesota Multiphasic Personality Inventory-2: an event-related potentials study.
AB  - On the basis of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), 20
      male students were separated in low (LP) versus high (HP) subjects with
      psychopathic tendencies. Pictures from the Ekman and Friesen series were used in
      an event-related potentials study to investigate the neurophysiological
      correlates of the emotional deficit described in psychopathy. Subjects were
      confronted with a visual oddball design, in which they had to detect, as quickly
      as possible, deviant happy, sad or fearful faces amongst a train of standard
      stimuli (neutral faces). Behavioral results suggest that LP subjects are more
      efficient in the detection of emotional deviant faces. This emotional deficit was
      neurophysiologically indexed, in HP subjects, by a decreased N300 component,
      which is supposed to be particularly sensitive to affective features of stimuli
      rather than to physical characteristics. Moreover, independently of the nature of
      the deviant faces, the P3a component shows an earlier latency in the HP group as
      compared to the LP group, whereas the reversed pattern was shown for the P3b
      component. Implications of these results were discussed.

PMID- 15555772
TI  - Visually cued motor synchronization: modulation of fMRI activation patterns by
      baseline condition.
AB  - A well-known issue in functional neuroimaging studies, regarding motor
      synchronization, is to design suitable control tasks able to discriminate between
      the brain structures involved in primary time-keeper functions and those related
      to other processes such as attentional effort. The aim of this work was to
      investigate how the predictability of stimulus onsets in the baseline condition
      modulates the activity in brain structures related to processes involved in time
      keeper functions during the performance of a visually cued motor synchronization
      task (VM). The rational behind this choice derives from the notion that using
      different stimulus predictability can vary the subject's attention and the
      consequently neural activity. For this purpose, baseline levels of BOLD activity
      were obtained from 12 subjects during a conventional-baseline condition:
      maintained fixation of the visual rhythmic stimuli presented in the VM task, and
      a random-baseline condition: maintained fixation of visual stimuli occurring
      randomly. fMRI analysis demonstrated that while brain areas with a documented
      role in basic time processing are detected independent of the baseline condition
      (right cerebellum, bilateral putamen, left thalamus, left superior temporal
      gyrus, left sensorimotor cortex, left dorsal premotor cortex and supplementary
      motor area), the ventral premotor cortex, caudate nucleus, insula and inferior
      frontal gyrus exhibited a baseline-dependent activation. We conclude that
      maintained fixation of unpredictable visual stimuli can be employed in order to
      reduce or eliminate neural activity related to attentional components present in
      the synchronization task.

PMID- 15555773
TI  - Angiotensin II induces proliferation of human cerebral artery smooth muscle cells
      through a basic fibroblast growth factor (bFGF) dependent mechanism.
AB  - Remodeling of cerebral arteries in hypertension produces thickened vessel walls
      associated with atherosclerotic plaque formation. In both thickening and plaque
      formation, proliferation of vascular smooth muscle cells is a hallmark.
      Genetically hypertensive rats treated with an angiotensin II (Ang II) AT1
      receptor antagonist inhibited thickening of cerebral arteries suggesting a
      mitogenic action of Ang II on cerebral arterial VSMC (CVSMC). However, in studies
      using smooth muscle cells cultured from peripheral arteries, Ang II causes cell
      hypertrophy, but not proliferation. We determined the effect of Ang II on
      proliferation of cultured human CVSMC. CVSMC were cultured from the basilar
      artery obtained at autopsy. Ang II (10(-7) M) stimulated proliferation determined
      by counting cells and mitochondrial activity assay. Synthesis and release of
      basic fibroblast growth factor (bFGF) was essential for Ang II-stimulated
      proliferation. These findings are consistent with the notion that Ang II
      stimulates CVSMC proliferation thereby contributing to vessel remodeling.

PMID- 15555774
TI  - alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-,
      but not beta-amyloid-induced neurotoxicity.
AB  - The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been
      implicated as a potential site of action for two neurotoxins, ethanol and the
      Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary
      neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to
      examine the role of this receptor in modulating the neurotoxic properties of
      subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene
      selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related
      fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however,
      was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not
      inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha
      bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol
      efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7
      nAChRs modulate the neurotoxic effects of binge ethanol, but not the
      neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of
      alpha7 nAChRs by ethanol provides partial protection against the neurotoxic
      properties of subchronic ethanol.

PMID- 15555775
TI  - Resistance in cell membrane and nerve fiber.
AB  - A mathematical model describing the resistance in cell membrane and nerve fiber
      is proposed, which is naturally different from that for metal conductors. An
      allometric scaling law between the resistance and the section area is obtained.
      In the derivation, He Chengtian's interpolation, which has millennia history, is
      applied. Most famous models, such as the Hodgkin-Huxley model, FitzHugh-Nagumo
      models, should be, therefore, revised.

PMID- 15555776
TI  - Very slow potentials in the lateral geniculate complex and primary visual cortex
      during different illumination changes in freely moving rats.
AB  - Previous literature has shown different forms of very slow oscillatory phenomena
      (0-0.5 Hz) in the structures of brain visual system. It was demonstrated in
      aforementioned publications that this infraslow activity might be sensitive to
      the level of environmental illumination. This study was performed to test the
      hypothesis that extracellular very slow brain potential (VSBP) oscillations or
      fluctuations in lateral geniculate complex (LGC) and primary visual cortex (PVC)
      are responding specifically and concurrently to different illumination changes.
      Experiments were conducted on five albino rats with chronically implanted
      stereotaxic electrodes in LGC and PVC brain sites. Our results support the
      aforementioned suggestion and revealed significant and similar patterns of VSBP
      modification within a frequency domain of seconds (0.1-0.25 Hz) in both the LGC
      and PVC in response to darkness, illumination and photostimulation. It is also
      documented here that significant and similar changes of multisecond activity
      (0.02-0.04 Hz) occur in both investigated brain sites in response to
      photostimulation only. Based on these findings, we propose that a possible role
      for VSBP oscillations in the LGC and PVC should be strongly considered in the CNS
      mechanisms of visual information processing.

PMID- 15555777
TI  - Chronic haloperidol or clozapine treatment does not alter parvalbumin
      immunoreactivity in the rat frontal cortex or hippocampus.
AB  - GABAergic neuronal subpopulations, defined by the presence of the calcium binding
      proteins, parvalbumin (PV) and calretinin (CR) are differentially affected in
      schizophrenia, with selective PV deficits reported in the prefrontal cortex and
      hippocampus. To assess the possible contribution of antipsychotic treatment to
      these effects we examined the size and density of PV-and CR-IR neurons in the rat
      frontal cortex and hippocampus following three weeks of chronic haloperidol or
      clozapine administration. Neither antipsychotic significantly altered PV- or CR
      IR neuronal cell parameters in these areas or in any of their subregions,
      relative to controls. These results suggest antipsychotic exposure does not
      contribute to PV-IR neuronal deficits in schizophrenic patients, providing
      further evidence in support of a developmental abnormality in specific
      subpopulations of GABAergic neurons in schizophrenia.

PMID- 15555778
TI  - Asymmetry of cortical activation during maximum and convenient tapping speed.
AB  - An effect of finger tapping rate on the hemodynamic response in primary motor
      cortex and the cerebellum has been well established over the last years (the rate
      effect). The present study compares the magnitude of this effect when either the
      dominant or subdominant hand is used by right and left handers. In contrast to
      previous studies maximum and convenient tapping rate for both hands are used as
      tapping tasks. The results confirm "rate effects" for the primary motor cortex
      and the cerebellum. In addition, a "rate effect" was found for the cingulate
      motor area. A novel finding is that the cortical and cerebellar "rate effects"
      are similar for the subdominant and for the dominant hand even though tapping
      rates are lower for the subdominant hand. This result demonstrates that the
      subdominant motor cortex and neurally connected cerebellar areas operate at
      suboptimal control levels although maximum neurophysiological activation has been
      reached during the maximum tapping task.

PMID- 15555779
TI  - Splice variants of the receptor for advanced glycosylation end products (RAGE) in
      human brain.
AB  - Previous studies indicate that the receptor for advanced glycosylation end
      products (RAGE) plays an important role in multiple pathological processes,
      including Alzheimer's disease. Currently there are three established isoforms of
      the RAGE receptor, with each isoform generated as the result of alternative
      splicing. It is presently unclear which of the RAGE isoforms are normally
      expressed in the human brain, nor has it been determined if additional RAGE
      isoforms exist in the human brain. In the present study we demonstrate for the
      first time that each of the three established RAGE isoforms, as well as three
      previously unidentified RAGE splicing variants, are normally expressed in the
      human brain. These data suggest that RAGE may have multiple functions in the
      human brain, mediated by the individual or coordinated efforts of the different
      RAGE isoforms, with alternative splicing generating individual RAGE isoforms that
      specifically interact with the various ligands present in the brain.

PMID- 15555780
TI  - Sexual dimorphism of activity-dependent neuroprotective protein in the mouse
      arcuate nucleus.
AB  - Activity-dependent neuroprotective protein (ADNP) is a highly conserved
      vasoactive intestinal peptide (VIP) responsive gene that is expressed abundantly
      in the brain and in the body and is essential for brain formation and embryonic
      development. Since, VIP exhibits sexual dimorphism in the hypothalamus, the
      potential differential expression of ADNP in male and female mice was
      investigated. Real-time polymerase chain reaction revealed sexual dimorphism in
      ADNP mRNA expression as well as fluctuations within the estrus cycle.
      Immunohistochemistry with an antibody to ADNP showed specific staining in the
      arcuate nucleus of the hypothalamus. ADNP-like immunoreactivity in the arcuate
      nucleus also exhibited fluctuations during the estrus cycle. Here, brain sections
      at proestrus were the most immunoreactive and brain sections at estrus--the
      least. Furthermore, male arcuate nucleus ADNP-like immunoreactivity was
      significantly lower than that of the female estrus. Many neuropeptides,
      neurotransmitters and proteins are localized to the arcuate nucleus where they
      contribute to the regulation of reproductive cyclicity and energy homeostasis.
      The results presented here suggest that ADNP has a part in the estrus cycle as an
      affecter or an effector.

PMID- 15555781
TI  - Enhancement of the NMDA receptor function by reduction of glycine transporter-1
      expression.
AB  - The occupation of the glycine binding-site is a prerequisite for NMDA receptor
      activation by glutamate. To analyze the regulation of NMDA receptor function by
      the glycine transporter 1 (GlyT1), we generated heterozygous constitutive GlyT1
      knockout mice (GlyT1tm1.1(+/-)). These animals were fully viable. Using a newly
      generated antibody, the pattern of GlyT1 expression in brain was found to be
      unaltered in the mutants while the level of expression was strongly reduced in
      all brain regions, as shown immunohistochemically. In hippocampal slices the
      ratio of the peak amplitude of NMDA and AMPA receptor evoked excitatory
      postsynaptic currents (EPSCs), recorded in CA1 pyramidal cells, was significantly
      enhanced by 36% in Glyt1tm1.1(+/-) compared to wild-type slices. The frequency
      and amplitude of AMPA miniature events in Glyt1tm1.1(+/-) mice were
      indistinguishable from those recorded in wild type. These results provide proof
      that the NMDA receptor function is enhanced by a reduction of GlyT1 expression.
      Thus, GlyT1 function is a controlling factor for an enhancement of the NMDA
      receptor response. These findings are of relevance for the development of GlyT1
      inhibitory drugs.

PMID- 15555783
TI  - Pain management.

PMID- 15555784
TI  - Infection control in burn patients.

PMID- 15555785
TI  - Care of burn patients in the hospital.

PMID- 15555786
TI  - Care of out patient burns.

PMID- 15555787
TI  - Outcome measures in burn care. Is mortality dead?
AB  - Health care systems constantly struggle with ways to provide higher quality care
      in a cost-effective manner. Outcome measures serve to evaluate what works and
      what does not. Whether they are used for research or for the improvement of
      clinical practice, they are as such, efficiency markers and the first step in
      determining the consequences of health care. The accomplishments of the past
      decade have placed us in the midst of an exciting paradigm shift from what used
      to be primary concern (i.e. mortality), to areas that are more likely to enhance
      the quality of life of burn survivors. Optimal management of severely burned
      persons is enormously expensive, and even after survival is ensured, may require
      a protracted period of surgical, medical and psychological rehabilitative
      measures for many years. This article aims to review the outcome measures in the
      acute phase of burn management (mortality and morbidity from the post-burn
      hypermetabolic response). We further discuss long-term outcome measures (such as,
      quality of life measures, exercise tolerance and evaluation of return to pre-burn
      activities) that are now becoming of equal importance as the numbers of burn
      survivors increase.

PMID- 15555788
TI  - The effect of essential oils on methicillin-resistant Staphylococcus aureus using
      a dressing model.
AB  - Patchouli, tea tree, geranium, lavender essential oils and Citricidal (grapefruit
      seed extract) were used singly and in combination to assess their anti-bacterial
      activity against three strains of Staphylococcus aureus: Oxford S. aureus NCTC
      6571 (Oxford strain), Epidemic methicillin-resistant S. aureus (EMRSA 15) and
      MRSA (untypable). The individual essential oils, extracts and combinations were
      impregnated into filter paper discs and placed on the surface of agar plates, pre
      seeded with the appropriate strain of Staphylococcus. The effects of the vapours
      of the oils and oil combinations were also assessed using impregnated filter
      paper discs that were placed on the underside of the Petri dish lid at a distance
      of 8mm from the bacteria. The most inhibitory combinations of oils for each
      strain were used in a dressing model constructed using a four layers of
      dressings: the primary layer consisted of either Jelonet or TelfaClear with or
      without Flamazine; the second was a layer of gauze, the third a layer of Gamgee
      and the final layer was Crepe bandage. The oil combinations were placed in either
      the gauze or the Gamgee layer. This four-layered dressing was placed over the
      seeded agar plate, incubated for 24h at 37 degrees C and the zones of inhibition
      measured. All experiments were repeated on three separate occasions. No anti
      bacterial effects were observed when Flamazine was smeared on the gauze in the
      dressing model. When Telfaclear was used as the primary layer in the dressing
      model compared to Jelonet, greater zones of inhibition were observed. A
      combination of Citricidal and geranium oil showed the greatest-anti-bacterial
      effects against MRSA, whilst a combination of geranium and tea tree oil was most
      active against the methicillin-sensitive S. aureus (Oxford strain). This study
      demonstrates the potential of essential oils and essential oil vapours as
      antibacterial agents and for use in the treatment of MRSA infection.

PMID- 15555789
TI  - The effect of N-acetylcysteine on oxidative stress in intestine and bacterial
      translocation after thermal injury.
AB  - Ischemia due to transient splanchnic vasoconstriction following major burns
      causes oxidative and/or nitrosative damage in intestinal tissue followed by
      reperfusion injury. Thus, burn injury leads to breakdown in the intestinal
      mucosal barrier which can induce bacterial translocation (BT). As an antioxidant
      and anti-inflammatory agent the protective effects of N-acetylcysteine (NAC) are
      documented in several studies. This study was designed to determine the effect of
      NAC treatment on the oxidative stress in the intestine and BT after burn injury.
      To evaluate this, 32 Wistar rats were randomly divided into four groups as sham
      (n = 8), burn (n = 8), pre-burn, NAC injection (150 mgkg(-1), intraperitoneally)
      15 min before thermal injury (n = 8), post-burn, NAC injection (150 mgkg(-1),
      intraperitoneally) 2h after thermal injury. Under anesthesia, the shaved dorsal
      skin of rats was exposed to boiling water for 12s to induce burn injury in a
      standardized manner. Twenty-four hours later, tissue samples from mesenteric
      lymph nodes (MLN), spleen, and liver were obtained under sterile conditions for
      microbiological analysis and ileum samples were harvested for biochemical
      analysis. In the burn group, the incidence of isolating bacteria in MLN, spleen,
      and liver specimens was significantly higher than other groups. NAC treatment
      prevented burn-induced BT in both pre- and post-burn groups. Thermal injury
      caused a significant decrease in glutathione (GSH) level, significant increases
      in malondialdehyde (MDA) and myeloperoxidase (MPO) activity at post-burn 24th
      hour. Treatment of rats with NAC significantly elevated the reduced GSH levels
      while decreasing MDA levels and MPO activity. These data suggested that NAC has a
      crucial cytoprotective role in intestinal mucosal barrier and preventive effects
      against burn injury-induced BT.

PMID- 15555790
TI  - The role of poly(ADP-ribose) synthetase inhibition on the intestinal mucosal
      barrier after thermal injury.
AB  - Oxidative and nitrosative stressor agents can trigger DNA strand breakage, which
      then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation
      of the enzyme depletes the intracellular concentration of energetic substrates
      such as nicotinamide adenine dinucleotide (NAD). This process can result in cell
      dysfunction and cell death. PARS inhibitors have been successfully used in
      ischemia-reperfusion injury, inflammation and sepsis in several experimental
      models. In our experimental study, we investigated the role of 3-aminobeanzamide
      (3-AB), a non-specific PARS inhibitor, on the intestinal mucosal barrier after
      burn injury. Twenty-four Wistar rats were randomly divided into three groups. The
      sham group (n = 8) was exposed to 21 degrees C water while the burn group (n = 8)
      and the burn + 3-AB group (n = 9) were exposed to boiling water for 12s to
      produce a full thickness burn in 35-40% of total body surface area. In the burn +
      3-AB group, 10mg/kg of 3-AB was given intraperitoneally 10min before thermal
      injury. Twenty-four hours later, tissue samples from mesenteric lymph nodes
      (MLN), spleen and liver were obtained under sterile conditions for
      microbiological analysis and ileum samples were obtained for biochemical and
      histopathological analysis. In burn group, the incidence of bacteria isolated
      from MLN and spleen was significantly higher than other groups (P < 0.05). 3-AB
      pre-treatment prevented burn induced bacterial translocation and it significantly
      reduced burn induced intestinal injury. Tissue malondialdehyde and 3
      nitrotyrozine levels were found significantly lower than that of the burn group.
      These data suggest that the relationship between PARS pathway and lipid
      peroxidation in intestinal tissue and PARS has a role in intestinal injury caused
      by thermal injury.

PMID- 15555791
TI  - Effect of early wound excision on changes in plasma nitric oxide and endothelin-1
      level after burn injury: an experimental study in rats.
AB  - The purpose of this study was to evaluate effects of early wound excision on
      changes in NO and endothelin-1 (ET-1) level in the plasma after extensive burn
      injury. The effects on vascular permeability and hepatic blood flow (HBF) were
      also assessed. Male Wistar rats were used for this study. A 30% total body
      surface area (TBSA) third-degree burn was made on the back. Then animals were
      divided into four groups. Burn group (n = 13), burn alone; infusion group (n =
      13), burn injury and fluid resuscitation; early excision group (n = 13), burn
      injury, total wound excision at 30 min after the injury followed with immediate
      allogenic skin graft and fluid resuscitation; and the sham group (n = 15). The
      sham group and the early excision group did not show significant changes in the
      NO and ET-1 level in plasma during experimental period, while the burn group and
      the infusion group showed significant increase in the NO and ET-1. The early
      excision group also did not show hypovolemia, and the significant decrease in the
      HBF. These data suggest that the increased NO and ET-1 in plasma following
      thermal injury were originated from burned tissue and the removal of these
      injured tissue has beneficial effect on the vascular permeability and the changes
      in HBF.

PMID- 15555792
TI  - A clinical randomized study on the effects of invasive monitoring on burn shock
      resuscitation.
AB  - BACKGROUND: Ever since Charles Baxter's recommendations the standard regime for
      burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn
      in the first 24h following the thermal injury. A growing number of studies on
      invasive monitoring in burn shock, however, have raised a debate regarding the
      adequacy of this regime. The purpose of this prospective, randomised study was to
      compare goal-directed therapy guided by invasive monitoring with standard care
      (Baxter formula) in patients with burn shock. PATIENTS AND METHODS: Fifty
      consecutive patients with burns involving more than 20% body surface area were
      randomly assigned to one of two treatment groups. The control group was
      resuscitated according to the Baxter formula (4 ml/kg BW/% BSA burn), the
      thermodilution (TDD) group was treated according to a volumetric preload endpoint
      (intrathoracic blood volume) obtained by invasive haemodynamic monitoring.
      RESULTS: The baseline characteristics of the two treatment groups were similar.
      Fluid administration in the initial 24h after burn was significantly higher in
      the TDD treatment group than in the control group (P = 0.0001). The results of
      haemodynamic monitoring showed no significant difference in preload or cardiac
      output parameters. Signs of significant intravasal hypovolemia as indicated by
      subnormal values of intrathoracic and total blood volumes were present in both
      treatment groups. Mortality and morbidity were independent on randomisation.
      CONCLUSION: Burn shock resuscitation due to the Baxter formula leads to
      significant hypovolemia during the first 48 h following burn. Haemodynamic
      monitoring results in more aggressive therapeutic strategies and is associated
      with a significant increase in fluid administration. Increased crystalloid
      infusion does not improve preload or cardiac output parameters. This may be due
      to the fact that a pure crystalloid resuscitation is incapable of restoring
      cardiac preload during the period of burn shock.

PMID- 15555793
TI  - Measures for preventing early postburn damage improve survival rate of burn
      patients.
AB  - AIM: To define the role of measures for preventing early postburn damage in
      improving the survival rate of burn patients. METHODS: 12568 burn cases admitted
      to our institute were chronologically divided into three groups (stages). Total
      burn surface area (TBSA), survival rate, incidence of burn shock, systemic
      infection and organ damage as well as the main treatments adopted in the recent
      decade were analyzed retrospectively. RESULTS: Incidence of burn shock, systemic
      infection and organ damage were significantly lower, and the total survival rate
      and the survival rate in patients with different TBSA were markedly higher in the
      third stage of the study as compared with those in the first and the second
      stages. The incidence of organ damage in patients treated with delayed fast fluid
      infusion, early extensive escharectomy, early enteral feeding, early intervention
      for inhalation injury and intervention to prevent gut bacterial translocation
      were also significantly lower than in those without the intervention resources.
      CONCLUSION: Measures for preventing early postburn damage play an important role
      in improving the survival rate of burn patients.

PMID- 15555794
TI  - Review of statistical data about severe burn patients treated during 2001 and
      evidence of septic cases in Albania.
AB  - The objective of this study is to review the incidence of severe burns and the
      complications of burns sepsis in Albanians. The data are from clinical records of
      the patients hospitalised in the intensive care unit (ICU) of the Service of
      Burns, "Mother Teresa" University Hospital Center (UHC), Tirana, Albania during
      2001. For the identification of sepsis in burned patients the classification of
      the American College of Chest Physicians/Society Critical Care Medicine
      (ACCP/SCCM) was used. All the cases were evaluated according to the clinical,
      diagnostic and laboratory data. The study presents some epidemiological data
      about the causative agent, the extent of burn, the depth of burn and the subjects
      injured. The study also identifies the pathogens responsible for the development
      of sepsis among patients. Such data was used to establish compound therapies
      focused on two or three antibiotics for each subject in order to treat sepsis and
      its possible complications. As a most important part of the treatment regime it
      is essential to identify patients at risk of sepsis, and to apply compound
      therapy with antibiotics in order to resist and treat this sepsis, which is the
      main cause of high mortality among our severely burned patients.

PMID- 15555795
TI  - Epidemiologic characteristics of death by burn injury from 1991 to 2001 in Korea.
AB  - This study was designed to investigate the epidemiologic characteristics of death
      from burn injury in Korea. We recoded the death certificate database from 1991 to
      2001 inclusive based on the short version of the International Classification of
      External Causes of Injuries (ICECI). Using variables such as sex, marital status,
      educational level, location of residence (metropolitan versus provincial), injury
      mechanism, and year, we calculated and compared the mortality rates and
      percentiles because of burn injury, and determined the adjusted odds ratio (OR)
      to assess the effect of socioeconomic factors on suicide deaths. The total number
      of deaths because of injury was 346,656, and the number of deaths because of burn
      injury was 9109 (2.6%), making burn injury the sixth leading cause of death from
      injury during the study period. The mortality rate due to burn injury was 1.8 per
      100,000 person-years in 2001, without long-term change from 1991. Major
      mechanisms of death included surface burns (80.7%), smoke inhalation (14.4%),
      respiratory burns (1.5%), and associated trauma (3.5%). The number of the suicide
      deaths was 466 from 1993 to 2001 inclusive, and the adjusted OR for suicide burns
      compared to accidental burns was significantly larger in the more highly
      educated, metropolitan, and married and divorced groups than it was in the never
      attended-school, provincial, and never-married groups, respectively.

PMID- 15555796
TI  - High incidence of suicide by burning in Masjid-i-Sulaiman (southwest of Iran), a
      polluted area with natural sour gas leakage.
AB  - Masjid-i-Sulaiman (MIS) is located in the southwest of Iran. Unfortunately, some
      parts of MIS are contaminated by subsurface leakage of natural gas containing
      H(2)S. In order to investigate the possible effect(s) of chronic exposure to
      sulfur compounds on suicidal behavior, the present study was done. In the 2-year
      period, 561 individuals attempted suicide (260 men and 301 women). Completed
      suicide comprised of 19 men and 32 women. The rate per 100,000 person-years was
      19.9 for men and 34.8 for women aged over 15 years. Forty-two (13 men and 29
      women) of 561 patients were self-immolators by fire with a male:female ratio
      0.45. This represents 22.4 burns per 100,000 person-years and is equivalent to
      7.4% of all suicide attempts. Thirty-three of 42 patients died (78.6%) who were 9
      men and 24 women with male:female ratio 0.37. There is statistically significant
      differences between sex groups (P((2)) = 0.0091). The self-inflicted burn was the
      most frequent method for lethal suicide. Winter was the most common season for
      self-burning followed by spring. Statistical analysis showed significant
      difference between seasons for self-inflicted burn (P((2)) = 0.00001). Analysis
      of correlation showed statistically positive correlation coefficient between mean
      values of all reactive sulfur compounds and seasonal frequency of suicide (r =
      0.923, P((1)) = 0.038).

PMID- 15555797
TI  - Self-inflicted burns: a sporadic phenomenon.
AB  - Self-inflicted burns are a regular cause of admission to burn units.
      Historically, a full moon has been associated with mental instability. Circadian
      rhythms and seasonal changes are known to influence human affect. Such cosmic
      effects, however, have not yet been studied for self-inflicted burns. In this
      regard, the results of a retrospective analysis of 184 self-inflicted burns
      admitted during a 20-year period to the Birmingham Burns Centre are presented.
      The analysis fails to show a connection between the timing of self-inflicted
      burns and cosmic events. Such incidents are random, not influenced by the day of
      the week, first or second half of the month, seasonal variation or phase of the
      lunar cycle.

PMID- 15555798
TI  - Burns in inpatients by simultaneous use of cigarettes and oxygen therapy.
AB  - Two inpatients with chronic obstructive pulmonary disease (COPD), treated with
      oxygen in the respiratory intensive care unit (RICU), sustained burns from
      explosion of oxygen delivery system while illicitly smoking. The authors discuss
      incidence and possible etiology with literature review.

PMID- 15555799
TI  - Work status and burn specific health after work-related burn injury.
AB  - Work status is a valid indicator of post burn health. There is limited
      information on this issue after work-related burn injury. AIM: To investigate
      long-term health- and work status after work-related burns. METHOD: Eighty-six
      former patients treated for severe work-related burn injuries an average of 9.0
      years previous to follow-up were questioned about their present work status. They
      were also assessed with the Burn Specific Health Scale-Brief (BSHS-B) and a pain
      scale adopted from the abbreviated Burn Specific Health Scale. RESULTS: At follow
      up 71 (83%) of the former patients were working, nine (10%) were on sick leave or
      had a disability pension, and six (7%) were unemployed. Those who were not
      working reported a poorer outcome in three of the BSHS-B psychosocial domains
      (Body Image, Affect and Interpersonal Relationships) and in two of the BSHS-B
      physical domains (Treatment Regimens and Work). They also reported significantly
      more pain. CONCLUSION: Only a small group of former patients with work-related
      accidents were not working in the sample studied after a long follow-up period.
      The unemployed reported more pain and worse perceived health, particularly in
      psychosocial domains.

PMID- 15555800
TI  - Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a
      preliminary report.
AB  - A prospective, non-comparative study design was used to describe our experience
      with a bromelain-derived debriding agent, Debridase, in 130 patients with 332
      deep second degree and third degree burns treated between 1984 and 1999.
      Debridase was applied after saturating the burns with a moist dressing for 2-24h.
      Debridase was applied for a period of 4h under an occlusive dressing. Mean
      patient age was 18.6 +/- 19.3, 42 (32.3%) were female, and 63 (48.5%) were
      children under age 18. Most burns were small. Debridase was applied once in 241
      (72.6%) of the 332 wounds, twice in 67 (20.18%) cases, three times in 12 (3.61%)
      cases, and four times in 2 (0.6%) cases. The percentage debridement by number of
      applications was 89 +/- 21% for a single application, 77 +/- 27% for two, and 62
      +/- 27% for three Debridase applications, respectively. There were no significant
      adverse events. The availability of a fast acting, reliable and complication-free
      enzymatic debriding agent may open new horizons and provide a new treatment
      modality for burns.

PMID- 15555801
TI  - Gabapentin for the treatment of itching produced by burns and wound healing in
      children: a pilot study.
AB  - We describe the use of gabapentin for the treatment of itching in wound healing
      in 35 children. All children were already treated with chlorpheniramine and
      trimeprazine but they remained irritable and were constantly rubbing their
      wounds. Within 24h of commencing treatment itching had improved significantly in
      all of the children.

PMID- 15555802
TI  - Acquired validity: a thermal injury history taking pitfall.

PMID- 15555803
TI  - Hot-air ballooning injuries in the United Kingdom (January 1976-January 2004).
AB  - OBJECTIVES: Injuries due to hot-air ballooning accidents are uncommon but may be
      severe. In this study we examined the factors contributing to ballooning
      accidents in the UK and the type of injuries sustained. METHODS: The post
      investigation reports of ballooning accidents from 1976 to 2004 were reviewed.
      They were analysed to determine type and severity of injuries, phase of flight at
      time of accident and causative or contributory factors. RESULTS: Sixty-one people
      were seriously injured in 98 ballooning accidents, with 2 fatalities. The
      majority of these accidents occurred during the approach and landing phase of
      flight. Ground collisions and crashes with power lines accounted for the majority
      of accidents. Adverse weather conditions were present in a significant number of
      crashes. Equipment failure was an uncommon cause of accidents. Fractures and
      burns were the most common form of injuries sustained. CONCLUSIONS: Changes in
      design and materials used, as well as adherence to specific recommended safety
      protocols, may aid to decrease the risk of severe burns in ballooning accidents.
      We discuss these factors illustrated by our experience of the worst recorded
      ballooning accident in Britain.

PMID- 15555804
TI  - Recurrent herpes simplex virus within autologous graft and healed burn scar--a
      case report.

PMID- 15555805
TI  - Scald from natural flex soothers--could design be safer?

PMID- 15555806
TI  - Burn from hair removal cream--a case report.

PMID- 15555807
TI  - Perianal burn as a complication of hemorrhoid treatment caused by hot water sitz
      bath.

PMID- 15555808
TI  - Unusual skin graft donor site in a full-thickness hand burn.

PMID- 15555809
TI  - Hot water bottle burn to reconstructed breast.

PMID- 15555810
TI  - The founding of the Pan African Burns Society.

PMID- 15555811
TI  - Drug abuse and suicidal behavior.

PMID- 15555812
TI  - Association of alcohol and drug use disorders and completed suicide: an empirical
      review of cohort studies.
AB  - BACKGROUND: This study updated and expanded upon Harris and Barraclough's
      empirical review [Harris, E.C., Barraclough, B., 1997. Suicide as an outcome for
      mental disorders. A meta-analysis, Br. J. Psychiatry 170, 205-228] of
      retrospective and prospective cohort studies of alcohol and drug use disorders
      and suicide. METHOD: Studies presenting data on alcohol and drug use disorders
      and suicide originally identified by Harris and Barraclough were used in this
      study. To find additional studies, (1) the location of English language reports
      on MEDLINE (1994-2002) were identified with the search terms 'substance
      disorders' with 'mortality' and 'follow-up', (2) read throughs were conducted of
      four prominent alcohol and drug specialty journals from 1966 through 2002, and
      (3) the reference sections of studies that met criteria were searched for
      additional reports. This strategy yielded 42 new studies meeting eligibility
      criteria. RESULTS: The estimated standardized mortality ratios (SMR; 95%
      confidence interval) for suicide were as follows: alcohol use disorder (979; 95%
      CI 898-1065; p < 0.001), opioid use disorder (1351; 95% CI 1047-1715; p < 0.001),
      intravenous drug use (1373; 95% CI 1029-1796; p < 0.001), mixed drug use (1685;
      95% CI 1473-1920; p < 0.001), heavy drinking (351; 95% CI 251-478; p < 0.001).
      SMR estimates stratified by sex were also calculated. CONCLUSIONS: Additional
      studies on the association of suicide and mixed drug use, heavy drinking, and
      alcohol use disorders in women augmented the findings of Harris and Barraclough,
      along with a novel estimate for intravenous drug use, a byproduct of intensive
      research on HIV in the past decade. There is a large empirical literature on
      alcohol use disorders and suicide and a moderate literature on suicide and opioid
      use disorders and IV drug use. There remains limited prospective data on the
      association of suicide and other drug use disorders (e.g., cocaine, cannabis).

PMID- 15555813
TI  - Suicidal behavior, drug use and depressive symptoms after detoxification: a 2
      year prospective study.
AB  - INTRODUCTION: Individuals with substance-related disorders are at increased risk
      for suicidal behavior. Identifying those at higher risk for suicide among this
      population is difficult and informed mainly on the basis of cross-sectional data.
      METHODS: We examined factors associated with drug-related suicidal behavior using
      multivariable regression analyses in a 2-year prospective study of 470 inpatients
      enrolled from an unlocked, detoxification unit. Suicidal behavior included
      suicidal ideation (SI) and suicide attempt (SA). RESULTS: Lifetime prevalence for
      SI was 28.5%, and for SA, 21.9%. During the 2-year follow-up, 19.9% of the sample
      endorsed suicidal ideation and 6.9% reported a suicide attempt. Correlates of
      lifetime suicidal behavior included younger age, female, Hispanic, greater
      depressive symptoms, past sexual abuse, and problem sedative or alcohol use.
      Factors associated with suicidal behavior at follow-up included past suicidal
      behavior, more depressive symptoms, and more frequent benzodiazepine and alcohol
      use. Cocaine and heroin use did not reach statistical significance. CONCLUSIONS:
      Suicidal behavior is common among individuals with substance-related disorders.
      Differences in "suicide potential" may exist between drug categories with CNS
      depressants increasing the risk. These findings highlight the importance of
      addressing the recurrent 'suicide risk' of patients with substance-related
      disorders and regular monitoring for changes in depressive symptoms and drug use.
      Based on the prevalence and severity of this problem, the role of universal
      suicide screening of individuals with substance-related disorders merits greater
      attention.

PMID- 15555814
TI  - Overview of workshop on drug abuse and suicidal behavior.

PMID- 15555815
TI  - Post-traumatic stress disorder, drug dependence, and suicidality among male
      Vietnam veterans with a history of heavy drug use.
AB  - This study examines the roles of post-traumatic stress disorder (PTSD) and drug
      dependence in non-fatal suicidality, i.e., suicidal ideation and suicide attempt,
      among Vietnam veterans in their adult years. The sample includes male veterans
      deployed to Vietnam, including an oversample of those who tested positive for
      opiates at their return (n = 642). PTSD, substance abuse, suicidality, and other
      psychopathology are analyzed using three waves of survey and military data
      covering the time period from early adolescence to middle adulthood. Measures
      include the onset and recency of each of the lifetime DSM-IV PTSD symptom
      criteria, and yearly symptom measures of DSM-IV dependence for alcohol and eight
      classes of psychoactive substances. Survival and hazard models are applied to
      assess the effects of drug dependence, PTSD, and other psychopathology on the
      duration of suicidality. Longitudinal models estimate the casual relationships
      among PTSD, drug dependence, and suicidality over a 25-year period. Results show
      evidence of strong continuity of PTSD, drug dependence, and suicidality over
      time. The causal role of drug dependence on PTSD and suicidality is limited to
      young adulthood. Evidence is stronger for self-medication in later adulthood. The
      results indicate that a life course perspective is needed for the combined
      treatment of PTSD and drug dependence for severely traumatized populations.

PMID- 15555816
TI  - Neurobehavior disinhibition in childhood predicts suicide potential and substance
      use disorder by young adulthood.
AB  - The objectives of this study were to (a) determine whether two factors that are
      established components of the risk for substance use disorder (SUD) also impact
      on the risk for suicide; and (2) evaluate whether SUD manifest by early adulthood
      predicts suicide propensity. Neurobehavior disinhibition assessed in 227 boys at
      ages 10-12 and 16 and parental history of SUD were prospectively evaluated to
      determine their association with the risk for SUD and suicide propensity between
      ages 16 and 19. The results indicated that neurobehavior disinhibition at age 16
      predicts suicide propensity between ages 16 and 19 (p = .04). A trend was
      observed (p = .08) for SUD manifest between ages 16 and 19 to predict suicide
      propensity during the same period. Maternal SUD is directly associated with son's
      SUD risk but not suicide propensity. Paternal SUD predicts son's neurobehavior
      disinhibition that, in turn, predisposes to SUD. A direct relation between
      paternal SUD and son's suicide propensity was not observed. These findings
      suggest that neurobehavior disinhibition, a component of the liability of SUD, is
      also associated with suicide risk. These results are discussed within a
      neurobehavioral framework in which prefrontal cortex dysfunction is hypothesized
      to underlie the risk for these two outcomes.

PMID- 15555817
TI  - The development of suicide ideation and attempts: an epidemiologic study of first
      graders followed into young adulthood.
AB  - Studying community residing youths originally recruited for an intervention trial
      upon entry into first grade, this project sought to estimate risk of suicide
      ideation and attempts to young adulthood, with focus on those who used drugs
      before age 16, as compared to youths who used later in development or not at all.
      Standardized interview assessments in 1989-1994 were completed with 2311 youths
      age 8-15. Roughly 15 years after recruitment, our study team reassessed 1695,
      nearly 75% of the survivors (mean age = 21), finding 155 to have made suicide
      attempts (SA) and 218 with onset of depression-related suicide ideation (SI). We
      estimate relative risk (RR), from survival analysis and logistic regression
      models, to study early use of tobacco, alcohol, cannabis, and inhalants, with
      covariate adjustments for age, sex, race-ethnicity, and other pertinent
      covariates. Early-onset of cannabis use and inhalant use for females, but not for
      males, signaled modestly excess risk of suicide attempt (cannabis-associated RR =
      1.9; p = 0.04; inhalant-associated RR = 2.2; p = 0.05). Early-onset of cannabis
      use by females (but not for males) signaled excess risk for suicide ideation (RR
      = 2.9; p = 0.006). Early-onset alcohol and tobacco use were not associated with
      later risk of SA or SI. In light of the relatively modest strength of
      association, the evidence may well reflect an underlying common diathesis or
      unmeasured prior confounding influences that link early-onset illegal drug use
      with later risk of these suicide-related events, rather than an influence of
      early-onset drug use per se.

PMID- 15555818
TI  - Paternal alcohol dependence and offspring suicidal behaviors in a children-of
      twins study.
AB  - INTRODUCTION: In substance abusing families, sources of familial comorbidity are
      potentially confounded by genetic-environmental (GE) interplays. The children-of
      twins (COT) design can be used to elucidate the association of a parental trait
      and an offspring outcome such as the association of parental alcoholism and
      offspring suicidality. METHODS: We examined the association of paternal
      alcoholism and offspring suicidal behaviors in an adolescent and young adult COT
      sample of 'Vietnam Era Twins' offspring who had completed an interview including
      a comprehensive assessment of lifetime suicidal behaviors. We stratified the COT
      sample into four groups contingent upon paternal zygosity, MZ versus DZ, and
      lifetime paternal alcohol dependence history (AD), positive versus negative. We
      examined whether the relationship of paternal alcoholism and offspring
      suicidality was best explained by genetic predispositions common to alcoholism
      and suicidality or by GE interplay--environmental influences correlated with
      parental alcoholism or the interaction of genetic and environmental factors.
      RESULTS: Our results suggest a main effect of paternal alcoholism on offspring
      suicide attempt; COT analyses do not support a purely genetic explanation for
      this association. DISCUSSION: Suicide attempts probably result from GE interplays
      and must be studied in genetically informative samples of offspring of substance
      abusing parents.

PMID- 15555819
TI  - Conceptual issues in understanding the relationship between suicidal behavior and
      substance use during adolescence.
AB  - Alcohol and drug use are considered to be risk factors for suicidal behaviors in
      adolescence, but the precise nature of the relationship between suicidality and
      substance abuse, and the implications of this relationship for prevention and
      treatment interventions remain elusive. There are several conceptual issues that
      need to be addressed when considering the substance abuse-suicidality
      relationship. What are the most appropriate ways of defining suicidal behaviors?
      What are the best ways of assessing suicidal behavior and characterizing its
      course over time? Should adolescents who are suicidal be considered to be a
      single homogeneous population? What are the possible ways in which the course of
      substance abuse and suicidality over time are related? What factors potentially
      affect the trajectories of both substance abuse and suicidality? Does the
      relationship between substance abuse and suicidality change over time? And, to
      what extent can our knowledge of factors precipitating and maintaining the joint
      outcomes of suicidal and substance abuse behaviors be incorporated into
      interventions that target both? Careful consideration and exploration of these
      issues hopefully should improve our understanding the substance abuse-suicidality
      interrelationship, and ultimately the development of more effective prevention
      efforts and treatments for youths with both problems.

PMID- 15555820
TI  - Suicidal behaviors and drug abuse: impulsivity and its assessment.
AB  - Impulsivity appears to play an important role in suicidal behaviors and drug
      abuse, which are two psychiatric problems that may interact with one another.
      Interpretation of the literature on impulsivity in these behaviors may be
      complicated by the variety of measurement techniques for the assessment of
      impulsivity. There are three general types of impulsivity assessment: self
      report, biological, and laboratory behavioral. Because laboratory behavioral
      measures both meet an operational definition of impulsivity and are sensitive to
      state-dependent changes in impulsivity, this paper presents data that focuses on
      laboratory behavioral performance among samples emitting suicidal behaviors or
      substance abuse. To better account for influence of impulsivity in these
      psychiatric disturbances, no single source of measurement should be used without
      the consideration of other types of instruments.

PMID- 15555821
TI  - Lower respiratory tract infections.

PMID- 15555822
TI  - Community-acquired pneumonia: pathophysiology and host factors with focus on
      possible new approaches to management of lower respiratory tract infections.
AB  - The present understanding of the pathophysiology of community-acquired pneumonia
      (CAP) explains the mechanism for many specific manifestations, but does not
      address adequately why only some patients experience complications. Recent
      advances in under-standing the genetics of complex illnesses offer hope for a
      more complete insight into the pathogenesis of CAP. This article reviews genetic
      variation in the molecules involved in the known patho-genic mechanisms of CAP,
      including cough, bacterial recognition, inflammation and the compensatory anti
      inflammatory response,and organ dysfunction.

PMID- 15555823
TI  - Epidemiology and etiology of community-acquired pneumonia.
AB  - The seriousness of community-acquired pneumonia (CAP), despite being a reasonably
      common and potentially lethal disease, often is under estimated by physicians and
      patients alike. CAP results in more than 10 million visits to physicians, 64
      million days of restricted activity, and 600,000 hospitalizations. This article
      discusses the epidemiology and bacterial causes of CAP in immunocompetent adults
      and the severe acute respiratory syndrome coronavirus.

PMID- 15555824
TI  - Antibacterial drug resistance: implications for the treatment of patients with
      community-acquired pneumonia.
AB  - In contrast to the tremendous number of articles and meetings devoted to
      elucidating the mechanisms of antibacterial drug resistance and describing the
      emergence of drug resistance patterns, little research has been completed on the
      impact of bacterial drug resistance on clinical outcomes. Moreover.among the
      studies that have been completed, the better-designed studies generally have
      failed to detect an effect of most current levels of antibacterial drug
      resistance on clinical outcomes for patients who have CAP. Yet, practice patterns
      are shifting in response to the perception that current levels of drug resistance
      necessitate changes in treatment patterns. This is unfortunate because it
      severely limits one's ability to continue to monitor the effectiveness of
      available therapies in light of changing patterns of antibacterial drug
      resistance. If levels of drug resistance continue to rise, it is likely that
      outcomes from those drug treatments will be affected adversely. In this regard,
      the recent licensing of a 7-valent pneumococcal conjugate vaccine for infants and
      young children may have an important effect on future trends in antibacterial
      drug resistance. The vaccine reduces childhood carriage of vaccine
      serotypes,which are among the most common serotypes found among drug-resistant
      isolates, and may reduce transmission of these serotypes to adults [65]. In
      conclusion, antibacterial drug resistance has not reduced substantially the
      effectiveness of first-line treatments for CAP. Whether levels of drug resistance
      will continue to increase or decline is unknown. Therefore,carefully designed
      outcomes studies likely will continue to be essential to help define optimal
      therapy for patients who have CAP.

PMID- 15555825
TI  - Community-acquired pneumonia: severity of illness evaluation.
AB  - Severity-of-illness assessment is now an accepted part of clinical practice and
      clinical research for the management of adults who have community-acquired
      pneumonia. Several approaches to this issue have been devised based on severity
      of-illness scores or rules, some related to site of management. No single
      approach has been found to be superior to others, but further research into their
      effect on outcome in clinical practice is required. It is likely that different
      approaches may suit different populations and health care systems.

PMID- 15555826
TI  - Diagnostic test for etiologic agents of community-acquired pneumonia.
AB  - Diagnostic tests for the detection of the etiologic agent of pneumonia are
      neither recommended nor done for most outpatients with CAP (Table 4).Most of
      these patients have no clear diagnosis but seem to do well with empiric
      antibiotic treatment, which often costs less than the diagnostic tests. For
      hospitalized patients, a pre-treatment blood culture and an expectorated sputum
      gram stain and culture should be done. Testing for Legionella spp is appropriate
      in hospitalized patients, especially those who are seriously ill. New tests that
      merit use in selected patients are the urinary antigen assay for S pneumoniae and
      the PCR test for L pneumophila. Anticipated developments in the near future are
      PCR tests for detection of C pneumoniae and M pneumoniae.

PMID- 15555827
TI  - Empiric treatment of ambulatory community-acquired pneumonia: always include
      treatment for atypical agents.
AB  - There are no data from proper studies to answer whether it is necessary to
      include antibiotics that are active against atypical pneumonia agents as part of
      the empiric therapy of CAP. Until such data are available, clinical judgment and
      severity of the pneumonic illness are the best guides to empiric antimicrobial
      therapy.

PMID- 15555828
TI  - Processes of care for community-acquired pneumonia.
AB  - Clinical and economic outcomes in hospitalized patients with CAP directly are
      related to the way that certain processes of care are executed at the local
      hospital level. For each process of care, a clear and evidence-based recommended
      course of action should be stated. Having an unambiguous action plan helps to
      develop process-of-care indicators and to educate healthcare workers. Improving
      processes of care is a secure way to improve outcomes in hospitalized patients
      with CAP.

PMID- 15555829
TI  - Acute exacerbations of chronic bronchitis: new developments concerning
      microbiology and pathophysiology--impact on approaches to risk stratification and
      therapy.
AB  - Exacerbations are a characteristic feature of chronic obstructive pulmonary
      disease and contribute significantly to associated morbidity and mortality.
      Renewed interest in this common clinical problem and research using new
      investigative tools has enhanced substantially the understanding of the
      pathogenesis of exacerbations. Results of recent clinical trials and
      observational studies have allowed refinements in treatment of exacerbations that
      should im-prove patient outcomes. This article discusses a rational, stratified
      approach to the use of antibiotics for this condition based on these recent
      studies.

PMID- 15555830
TI  - Nonresponses and treatment failures with conventional empiric regimens in
      patients with community-acquired pneumonia.
AB  - Although most patients with suspected CAP respond to empiric therapy,a small
      number of patients do not respond in the expected fashion. Age and underlying
      comorbid conditions have a strong influence on the course of illness. Less common
      causes of treatment failures include overwhelming infection, antimicrobial
      resistance, and misdiagnosis. It is a common practice for empiric antimicrobial
      treatment of CAP to be initiated without microbiologic studies. Clinicians
      carefully should observe these patients for unusual or slow responses and should
      be ready to pursue a more extensive search for the cause of treatment failure.

PMID- 15555831
TI  - Lower respiratory tract infections: prevention using vaccines.
AB  - In summary, vaccines are available to prevent two of the most common and most
      deadly causes of lower respiratory tract infections: pneumococcal disease and
      influenza. Pneumococcal polysaccharide vaccine prevents pneumococcal bacteremia;
      influenza vaccines prevent influenza as well as several complications of
      influenza. Despite all that is known about how well these vaccines work,
      influenza and pneumococcal vaccines are underused markedly, especially among some
      minority groups that are affected dis-proportionately by disease. Coverage also
      remains low among health care workers, although providing influenza vaccine to
      health care workers saves lives among patients. Tools such as standing orders can
      help clinicians increase vaccine coverage in their patient populations. While
      research for new and improved vaccines to prevent lower respiratory tract
      infections continues,focusing on simple measures for increasing vaccine use can
      help prevent morbidity and mortality now.

PMID- 15555832
TI  - Management of acute bronchitis in healthy adults.
AB  - Acute respiratory infections (ARIs) are the most common infections in humans,
      accounting for half of all acute conditions each year in the United States. Acute
      bronchitis episodes represent a significant portion of these illnesses. This
      article focuses on acute bronchitis in otherwise healthy individuals.

PMID- 15555833
TI  - Healthcare-associated pneumonia in adults: management principles to improve
      outcomes.
AB  - Guidelines for Management of HAP were developed jointly by the ATS and IDSA in
      2004. These guidelines were designed to improve patient outcomes and to decrease
      the emergence of MDR pathogens (see Fig. 1).Principles include early initiation
      of appropriate and adequate antibiotic therapy after cultures of blood and sputum
      are obtained. Quantitative distal airway sampling by bronchoscopy provides
      greater diagnostic specificity for VAP: in one randomized study, improved
      outcomes were noted, compared with clinical diagnosis with qualitative
      endotracheal aspirates. Higher doses of initial, empiric antibiotics also are
      recommended. Assessment of the patient's clinical response to empiric antibiotics
      should be correlated with microbiologic results to streamline, de-escalate, or
      stop unnecessary anti-biotic treatment. Duration of therapy for uncomplicated HAP
      should be limited to 7 days followed by close monitoring for relapse after
      cessation of antibiotics. The authors suggest that prevention strategies target
      modifiable short- and long-term risk factors. They also advocate the use of a
      multidisciplinary team that is dedicated to the treatment and prevention of HCAP
      and the basic principle of the modern Hippocratic Oath: "I will prevent disease
      whenever I can, for prevention is preferable to cure."

PMID- 15555835
TI  - Local guidelines for community-acquired pneumonia: development, implementation,
      and outcome studies.
AB  - Published outcome studies mostly report a positive effect of successfully
      implemented pneumonia guidelines. Confirmatory studies are needed that use
      randomized, parallel groups with precisely defined treatments, however. Further
      research also is needed to develop methodology for more easily providing
      guideline logic to clinicians at the point of care.

PMID- 15555834
TI  - Re-evaluation of the therapy of severe pneumonia caused by Streptococcus
      pneumoniae.
AB  - Pneumonia caused by Streptococcus pneumoniae is the most deadly form of community
      acquired pneumonia. The death rate of bacteremic pneumococcal pneumonia has
      remained constant over the past 50 years. Several retrospective reviews of
      bacteremic pneumococcal pneumonia suggest that dual therapy with a beta-lactam
      and a macrolide antimicrobial agent is associated with a lower case fatality rate
      than therapy with a beta-lactam alone. These studies are reviewed, potential
      mechanisms are suggested, and future studies are discussed.

PMID- 15555836
TI  - Antimicrobial therapy of community-acquired pneumonia.
AB  - Community-acquired pneumonia (CAP) is a common disorder that is potentially life
      threatening, especially in older adults and patients with comorbid disease.
      Despite substantial progress in therapeutic options, CAP remains a primary cause
      of death from infectious disease in the United States. The mainstay of treatment
      for most patients is appropriate antimicrobial therapy This article reviews the
      principles for initial antimicrobial therapy, highlights some of the differences
      in approaches to antimicrobial drug selection in selected guidelines, and
      includes new recommendations for empiric and pathogen-directed therapy of CAP.

PMID- 15555839
TI  - Pathologic conditions of the plantar fascia.
AB  - Plantar heel pain in adults is commonly seen in the office of the podiatric foot
      and ankle specialist. These symptoms may have developed acutely or over a period
      of time. Often the plantar fascia is the source of the pain, which is caused by a
      traumatic event or a biomechanical flaw. It is imperative that the podiatric
      physician understands the multiple causes of plantar foot pain and is able to
      differentiate the multiple causes of heel pain to confirm a specific diagnosis
      and formulate a proper treatment plan. A thorough history and physical
      examination are necessary to obtain this information, and diagnostic procedures
      are sometimes needed.

PMID- 15555840
TI  - Plantar fibromatosis.
AB  - Plantar fibromatosis is defined as a benign fibrous disorder involving the
      plantar aponeurosis. Although its incidence is well described on the hands, it is
      less commonly seen on the feet, and its etiology is unknown. A differential
      diagnosis for the heel pain along the medial arch could be a benign thickening of
      the plantar fascia associated with plantar fibromatosis. Its high recurrence
      after surgical excision and problematic scarring and wound presents a significant
      challenge to the reconstructive foot and ankle surgeon. This article reviews the
      history, clinical presentation, pathologic findings, and surgical approaches to
      the treatment of plantar fibromatosis.

PMID- 15555841
TI  - Posterior heel pain (retrocalcaneal bursitis, insertional and noninsertional
      Achilles tendinopathy).
AB  - The majority of patients with Achilles tendinopathy respond to nonoperative
      treatment. In patients with refractory symptoms, surgery can be considered. If
      paratenonitis is present, the paratenon is partially excised, and adhesions are
      released. Areas of symptomatic tendinosis are excised with repair of the residual
      defect in the Achilles tendon. An alternative for patients with tendinosis who
      are at increased risk for wound problems or who do not want a large open incision
      is percutaneous or endoscopic tenotomy. A symptomatic Haglund's deformity or
      inflamed retrocalcaneal bursa is excised. Augmentation of the Achilles tendon may
      be considered if debridement threatens the structural integrity of the tendon, in
      older patients, and in revision surgery.

PMID- 15555842
TI  - Calcaneal stress fractures.
AB  - The majority of plantar heel pain is diagnosed as plantar fasciitis or heel spur
      syndrome. When historic or physical findings are unusual or when routine
      treatment proves ineffective, one should consider an atypical cause of heel pain.
      Stress fractures of the calcaneus are a frequently unrecognized source of heel
      pain. In some cases they can continue to go unrecognized because the symptoms of
      calcaneal stress fractures sometimes improves with treatments aimed at plantar
      fasciitis. Calcaneal stress fractures can occur in any population of adults and
      even children and are common among active people, such as athletes, sports
      enthusiasts, and military personnel. It is likely that the number of diagnosed
      calcaneal stress fractures will rise among practitioners with an increased
      recognition of their possibility.

PMID- 15555843
TI  - Calcaneal apophysitis (Sever disease).
AB  - Calcaneal apophysitis is a painful inflammation of the calcaneal apophysis
      believed to be caused by repetitive microtrauma from the pull of the Achilles
      tendon on the unossified apophysis. It frequently occurs before or during the
      peak growth spurt and often shortly after a child begins a new sport or season.
      Coaches and parents should be aware of the clinical symptoms of Sever disease so
      that early protective and proactive measures and appropriate treatment can be
      instituted.

PMID- 15555844
TI  - Sinus tarsi syndrome and subtalar joint instability.
AB  - Sinus tarsi syndrome is a poorly understood term in the orthopedic world. It is
      thought of as a painful condition of the sinus tarsi that often responds to
      corticosteroid injection and is associated with a feeling of instability in the
      hindfoot. Despite references in the literature, there is no agreement on
      pathognomonic history, clinical tests, or imaging studies that could help in
      confirming the diagnosis or establishing the etiology. Some authors relate the
      clinical condition of sinus tarsi syndrome with instability of the subtalar
      joint.

PMID- 15555845
TI  - Peroneal tendon pathology.
AB  - Peroneal tendon pathology is a common entity but is infrequently reported in the
      literature. The lesion may be due to partial tears, complete ruptures,
      subluxation, tenosynovitis, a fractured os peroneum, or damage to the peroneal
      retinacula. Chronic lateral ankle instability and excessive subtalar and ankle
      varus rotation may cause damage to the peroneal tendons and their associated
      structures. This article reviews the pathophysiology, diagnostic imaging, and
      current surgical techniques for the repair of peroneal tendons.

PMID- 15555846
TI  - Disorders of the Achilles tendon and its insertion.
AB  - This article describes disorders of the Achilles tendon and its insertion.

PMID- 15555847
TI  - Neurogenic heel pain.
AB  - This article establishes a standard approach for the evaluation of patients with
      heel pain. With this approach, it should become easier for the physician to
      distinguish between neurogenic and inflammatory heel pain and to devise a more
      direct plan for definitive treatment.

PMID- 15555848
TI  - Pathologic conditions of the heel: tumors and arthritides.
AB  - Heel pain is one of the most common presenting complaints to the foot and ankle
      specialist. There are many causes for subcalcaneal heel pain, including
      biomechanical, traumatic, those related to several types of arthritides and
      tumors, and anatomic causes. This article describes pathologic conditions of the
      heel, concentrating on tumors and arthritides.

PMID- 15555850
TI  - Self-organization of globally continuous and locally distributed information
      representation.
AB  - A number of findings suggest that the preferences of neighboring neurons in the
      inferior temporal (IT) cortex of macaque monkeys tend to be similar. However, a
      recent study reports convincingly that the preferences of neighboring neurons
      actually differ. These findings seem contradictory. To explain this conflict, we
      propose a new view of information representation in the IT cortex. This view
      takes into account sparse and local neuronal excitation. Since the excitation is
      sparse, information regarding visual objects seems to be encoded in a distributed
      manner. The local excitation of neurons coincides with the classical notion of a
      column structure. Our model consists of input layer and output layer. The main
      difference from conventional models is that the output layer has local and random
      intra-layer connections. In this paper, we adopt two rings embedded in three
      dimensional space as an input signal space, and examine how resultant information
      representation depends on the distance between two rings that is denoted as D. We
      show that there exists critical value for the distance Dc. When D > Dc the output
      layer becomes able to form the column structure, this model can obtain the
      distributed representation within the column. While the output layer acquires the
      conventional information representation observed in the V1 cortex when D < Dc.
      Moreover, we consider the origin of the difference between information
      representation of the V1 cortex and that of the IT cortex. Our finding suggests
      that the difference in the information representations between the V1 and the IT
      cortices could be caused by difference between the input space structures.

PMID- 15555851
TI  - A comparative investigation on subspace dimension determination.
AB  - It is well-known that constrained Hebbian self-organization on multiple linear
      neural units leads to the same k-dimensional subspace spanned by the first k
      principal components. Not only the batch PCA algorithm has been widely applied in
      various fields since 1930s, but also a variety of adaptive algorithms have been
      proposed in the past two decades. However, most studies assume a known dimension
      k or determine it heuristically, though there exist a number of model selection
      criteria in the literature of statistics. Recently, criteria have also been
      obtained under the framework of Bayesian Ying-Yang (BYY) harmony learning. This
      paper further investigates the BYY criteria in comparison with existing typical
      criteria, including Akaike's information criterion (AIC), the consistent Akaike's
      information criterion (CAIC), the Bayesian inference criterion (BIC), and the
      cross-validation (CV) criterion. This comparative study is made via experiments
      not only on simulated data sets of different sample sizes, noise variances, data
      space dimensions, and subspace dimensions, but also on two real data sets from
      air pollution problem and sport track records, respectively. Experiments have
      shown that BIC outperforms AIC, CAIC, and CV while the BYY criteria are either
      comparable with or better than BIC. Therefore, BYY harmony learning is a more
      preferred tool for subspace dimension determination by further considering that
      the appropriate subspace dimension k can be automatically determined during
      implementing BYY harmony learning for the principal subspace while the selection
      of subspace dimension k by BIC, AIC, CAIC, and CV has to be made at the second
      stage based on a set of candidate subspaces with different dimensions which have
      to be obtained at the first stage of learning.

PMID- 15555852
TI  - Recursive self-organizing network models.
AB  - Self-organizing models constitute valuable tools for data visualization,
      clustering, and data mining. Here, we focus on extensions of basic vector-based
      models by recursive computation in such a way that sequential and tree-structured
      data can be processed directly. The aim of this article is to give a unified
      review of important models recently proposed in literature, to investigate
      fundamental mathematical properties of these models, and to compare the
      approaches by experiments. We first review several models proposed in literature
      from a unifying perspective, thereby making use of an underlying general
      framework which also includes supervised recurrent and recursive models as
      special cases. We shortly discuss how the models can be related to different
      neuron lattices. Then, we investigate theoretical properties of the models in
      detail: we explicitly formalize how structures are internally stored in different
      context models and which similarity measures are induced by the recursive mapping
      onto the structures. We assess the representational capabilities of the models,
      and we shortly discuss the issues of topology preservation and noise tolerance.
      The models are compared in an experiment with time series data. Finally, we add
      an experiment for one context model for tree-structured data to demonstrate the
      capability to process complex structures.

PMID- 15555853
TI  - Improved learning of Riemannian metrics for exploratory analysis.
AB  - We have earlier introduced a principle for learning metrics, which shows how
      metric-based methods can be made to focus on discriminative properties of data.
      The main applications are in supervising unsupervised learning to model
      interesting variation in data, instead of modeling all variation as plain
      unsupervised learning does. The metrics are derived by approximations to an
      information-geometric formulation. In this paper, we review the theory, introduce
      better approximations to the distances, and show how to apply them in two
      different kinds of unsupervised methods: prototype-based and pairwise distance
      based. The two examples are self-organizing maps and multidimensional scaling
      (Sammon's mapping).

PMID- 15555854
TI  - Stability of generalized topographic mappings between cell layers through
      correlational learning.
AB  - We propose a simple topographic mapping formation model from a cell layer to a
      cell layer. Our model is a discrete one in that the state value of input and
      output cells takes 0 or 1 and input and output layers are represented by
      undirected graphs. A binary input pattern can be given to the network consisting
      of input and output cell layers. Such an input pattern can be represented by a
      subset of input cells. That is, a state value of an input cell takes 1 if a cell
      belongs to the subset, otherwise, a state value of an input cell is 0. Such a
      definition of an input pattern does not necessarily assume a short-range
      excitatory mechanism in an input layer. Thus, a topographic mapping described in
      this model is a map, which preserves the input pattern relation. By using the
      concept of input pattern separability, we showed an existence condition of
      certain learning rules, which are correlational. We have paid special attention
      to such correlational type learning rules, and have shown under the rules that
      topographic mappings are the only stable ones. As to the non-correlational
      learning rules, we also investigate the stability of generated mappings.

PMID- 15555855
TI  - Synaptic weight normalization effects for topographic mapping formation.
AB  - We propose a simple topographic mapping formation model between cell layers with
      weight normalization. In our model, each cell layer can have an arbitrary
      neighborhood relation between the cells represented by an undirected graph. Thus,
      a topographic mapping described in this model is a map which preserves the
      adjacency relation. We define several learning rules, input and output type
      weight normalization methods. Then, we not only concentrate on a Hebbean weight
      modification but also investigate the effects of normalization under a non
      Hebbean weight modification. We first show that when an input type normalization
      is adopted or without normalization, a topographic mapping is stable under the
      correlational type learning rule, but when an output type normalization is
      adopted a topographic mapping is stable under not only the correlational type
      learning rule but also the non-correlational one. Next, we show by computer
      simulations that when an output type normalization is considered we have more
      learning rules which yield topographic mappings than the cases when an input type
      normalization is adopted or without normalization.

PMID- 15555856
TI  - Class distributions on SOM surfaces for feature extraction and object retrieval.
AB  - A Self-Organizing Map (SOM) is typically trained in unsupervised mode, using a
      large batch of training data. If the data contain semantically related object
      groupings or classes, subsets of vectors belonging to such user-defined classes
      can be mapped on the SOM by finding the best matching unit for each vector in the
      set. The distribution of the data vectors over the map forms a two-dimensional
      discrete probability density. Even from the same data, qualitatively different
      distributions can be obtained by using different feature extraction techniques.
      We used such feature distributions for comparing different classes and different
      feature representations of the data in the context of our content-based image
      retrieval system PicSOM. The information-theoretic measures of entropy and mutual
      information are suggested to evaluate the compactness of a distribution and the
      independence of two distributions. Also, the effect of low-pass filtering the SOM
      surfaces prior to the calculation of the entropy is studied.

PMID- 15555857
TI  - Robust growing neural gas algorithm with application in cluster analysis.
AB  - We propose a novel robust clustering algorithm within the Growing Neural Gas
      (GNG) framework, called Robust Growing Neural Gas (RGNG) network.The Matlab codes
      are available from . By incorporating several robust strategies, such as outlier
      resistant scheme, adaptive modulation of learning rates and cluster repulsion
      method into the traditional GNG framework, the proposed RGNG network possesses
      better robustness properties. The RGNG is insensitive to initialization, input
      sequence ordering and the presence of outliers. Furthermore, the RGNG network can
      automatically determine the optimal number of clusters by seeking the extreme
      value of the Minimum Description Length (MDL) measure during network growing
      process. The resulting center positions of the optimal number of clusters
      represented by prototype vectors are close to the actual ones irrespective of the
      existence of outliers. Topology relationships among these prototypes can also be
      established. Experimental results have shown the superior performance of our
      proposed method over the original GNG incorporating MDL method, called GNG-M, in
      static data clustering tasks on both artificial and UCI data sets.

PMID- 15555858
TI  - SOM-based algorithms for qualitative variables.
AB  - It is well known that the SOM algorithm achieves a clustering of data which can
      be interpreted as an extension of Principal Component Analysis, because of its
      topology-preserving property. But the SOM algorithm can only process real-valued
      data. In previous papers, we have proposed several methods based on the SOM
      algorithm to analyze categorical data, which is the case in survey data. In this
      paper, we present these methods in a unified manner. The first one (Kohonen
      Multiple Correspondence Analysis, KMCA) deals only with the modalities, while the
      two others (Kohonen Multiple Correspondence Analysis with individuals, KMCA_ind,
      Kohonen algorithm on DISJonctive table, KDISJ) can take into account the
      individuals, and the modalities simultaneously.

PMID- 15555859
TI  - Double quantization of the regressor space for long-term time series prediction:
      method and proof of stability.
AB  - The Kohonen self-organization map is usually considered as a classification or
      clustering tool, with only a few applications in time series prediction. In this
      paper, a particular time series forecasting method based on Kohonen maps is
      described. This method has been specifically designed for the prediction of long
      term trends. The proof of the stability of the method for long-term forecasting
      is given, as well as illustrations of the utilization of the method both in the
      scalar and vectorial cases.

PMID- 15555860
TI  - Making sense of sparse rating data in collaborative filtering via topographic
      organization of user preference patterns.
AB  - We introduce topographic versions of two latent class models (LCM) for
      collaborative filtering. Latent classes are topologically organized on a square
      grid. Topographic organization of latent classes makes orientation in
      rating/preference patterns captured by the latent classes easier and more
      systematic. The variation in film rating patterns is modelled by multinomial and
      binomial distributions with varying independence assumptions. In the first stage
      of topographic LCM construction, self-organizing maps with neural field organized
      according to the LCM topology are employed. We apply our system to a large
      collection of user ratings for films. The system can provide useful visualization
      plots unveiling user preference patterns buried in the data, without loosing
      potential to be a good recommender model. It appears that multinomial
      distribution is most adequate if the model is regularized by tight grid
      topologies. Since we deal with probabilistic models of the data, we can readily
      use tools from probability and information theories to interpret and visualize
      information extracted by our system.

PMID- 15555861
TI  - Plastic mine detecting radar system using complex-valued self-organizing map that
      deals with multiple-frequency interferometric images.
AB  - Ground penetrating radars (GPR's) have been often applied to underground object
      imaging. However, conventional radar systems do not work sufficiently to detect
      anti-personnel plastic landmines. We propose a novel radar imaging system, which
      processes adaptively interferometric front-end data obtained at multiple
      frequency points. The system deals with interferometric images using complex
      valued self-organizing map (C-SOM). We demonstrate a successful visualization of
      a plastic mine buried near the ground surface.

PMID- 15555862
TI  - Self-organizing maps and clustering methods for matrix data.
AB  - In this contribution we present extensions of the Self Organizing Map and
      clustering methods for the categorization and visualization of data which are
      described by matrices rather than feature vectors. Rows and Columns of these
      matrices correspond to objects which may or may not belong to the same set, and
      the entries in the matrix describe the relationships between them. The clustering
      task is formulated as an optimization problem: Model complexity is minimized
      under the constraint, that the error one makes when reconstructing objects from
      class information is fixed, usually to a small value. The data is then visualized
      with help of modified Self Organizing Maps methods, i.e. by constructing a
      neighborhood preserving non-linear projection into a low-dimensional "map-space".
      Grouping of data objects is done using an improved optimization technique, which
      combines deterministic annealing with "growing" techniques. Performance of the
      new methods is evaluated by applying them to two kinds of matrix data: (i)
      pairwise data, where row and column objects are from the same set and where
      matrix elements denote dissimilarity values and (ii) co-occurrence data, where
      row and column objects are from different sets and where the matrix elements
      describe how often object pairs occur.

PMID- 15555863
TI  - Online algorithm for the self-organizing map of symbol strings.
AB  - In this work an online algorithm is presented for the construction of the self
      organizing map (SOM) of symbol strings. Each node of the SOM grid is associated
      with a model string which is a variable-vector sequence. Smooth interpolation
      method is applied in the training which performs simultaneous adaptation of the
      symbol content and the length of the model string. The efficiency of the method
      is demonstrated by the clustering of a 100,000-word English dictionary.

PMID- 15555864
TI  - Self-organizing semantic maps and its application to word alignment in Japanese
      Chinese parallel corpora.
AB  - This paper presents a method involving self-organizing monolingual semantic maps
      that are visible and continuous representations where Chinese or Japanese words
      with similar meanings are placed at the same or neighboring points so that the
      distance between them represents the semantic similarity. We used the self
      organizing map, SOM, as a self-organizing device. The words to be self-organized
      are defined by sets of co-occurring words collected from Chinese or Japanese
      newspapers, according to their grammatical relationships. The words are then
      coded into vectors to be forwarded to the SOM, taking into account the semantic
      correlation between them, which is established using a form of word-similarity
      computation. The self-organized monolingual semantic maps are assessed by
      numerical evaluations of accuracy, recall, and the F-measure, as well as by
      intuition, and by the comparisons with a clustering method and with multivariate
      statistical analysis. This paper further discusses the possibility that the
      method we propose can be extended to constructing Japanese-Chinese bilingual
      semantic maps, with the aim of providing a semantics-based approach to word
      alignment in Japanese-Chinese parallel corpora. We also show the effectiveness of
      this extended method through small-scale comparative experiments with a baseline
      method, where the alignment of Japanese and Chinese words is directly determined
      through the Euclidean distance of vectors representing the words, with a
      clustering method, and with multivariate statistical analysis.

PMID- 15555865
TI  - Adaptive topological tree structure for document organisation and visualisation.
AB  - The self-organising map (SOM) is finding more and more applications in a wide
      range of fields, such as clustering, pattern recognition and visualisation. It
      has also been employed in knowledge management and information retrieval. We
      propose an alternative to existing 2-dimensional SOM based methods for document
      analysis. The method, termed Adaptive Topological Tree Structure (ATTS),
      generates a taxonomy of underlying topics from a set of unclassified,
      unstructured documents. The ATTS consists of a hierarchy of adaptive self
      organising chains, each of which is validated independently using a proposed
      entropy-based Bayesian information criterion. A node meeting the expansion
      criterion spans a child chain, with reduced vocabulary and increased
      specialisation. The ATTS creates a topological tree of topics, which can be
      browsed like a content hierarchy and reflects the connections between related
      topics at each level. A review is also given on the existing neural network based
      methods for document clustering and organisation. Experimental results on real
      world datasets using the proposed ATTS method are presented and compared with
      other approaches. The results demonstrate the advantages of the proposed
      validation criteria and the efficiency of the ATTS approach for document
      organisation, visualisation and search. It shows that the proposed methods not
      only improve the clustering results but also boost the retrieval.

PMID- 15555866
TI  - Self-organization of distributedly represented multiple behavior schemata in a
      mirror system: reviews of robot experiments using RNNPB.
AB  - The current paper reviews a connectionist model, the recurrent neural network
      with parametric biases (RNNPB), in which multiple behavior schemata can be
      learned by the network in a distributed manner. The parametric biases in the
      network play an essential role in both generating and recognizing behavior
      patterns. They act as a mirror system by means of self-organizing adequate memory
      structures. Three different robot experiments are reviewed: robot and user
      interactions; learning and generating different types of dynamic patterns; and
      linguistic-behavior binding. The hallmark of this study is explaining how self
      organizing internal structures can contribute to generalization in learning, and
      diversity in behavior generation, in the proposed distributed representation
      scheme.

PMID- 15555867
TI  - Motor primitive and sequence self-organization in a hierarchical recurrent neural
      network.
AB  - This study describes how complex goal-directed behavior can be obtained through
      adaptation processes in a hierarchically organized recurrent neural network using
      a genetic algorithm (GA). Our experiments, using a simulated Khepera robot,
      showed that different types of dynamic structures self-organize in the lower and
      higher levels of the network for the purpose of achieving complex navigation
      tasks. The parametric bifurcation structures that appear in the lower level
      explain the mechanism of how behavior primitives are switched in a top-down way.
      In the higher level, a topologically ordered mapping of initial cell activation
      states to motor primitive sequences self-organizes by utilizing the initial
      sensitivity characteristics of non-linear dynamical systems. The biological
      plausibility of the model's essential principles is discussed.

PMID- 15555868
TI  - Maplets for correspondence-based object recognition.
AB  - We present a correspondence-based system for visual object recognition with
      invariance to position, orientation, scale and deformation. The system is
      intermediate between high- and low-dimensional representations of
      correspondences. The essence of the approach is based on higher-order links,
      called here maplets, which are specific to narrow ranges of mapping parameters
      (position, scale and orientation), which interact cooperatively with each other,
      and which are assumed to be formed by learning. While being based on dynamic
      links, the system overcomes previous problems with that formulation in terms of
      speed of convergence and range of allowed variation. We perform face recognition
      experiments, comparing ours to other published systems. We see our work as a step
      towards a reformulation of neural dynamics that includes rapid network self
      organization as essential aspect of brain state organization.

PMID- 15555869
TI  - Fully automated biomedical image segmentation by self-organized model adaptation.
AB  - In this paper, we present a fully automated image segmentation method based on an
      algorithm that provides adaptive plasticity in function approximation problems:
      the deformable (feature) map (DM) algorithm. The DM approach reduces a class of
      similar function approximation problems to the explicit supervised one-shot
      training of a single data set. This is followed by a subsequent, appropriate
      similarity transformation, which is based on a self-organized deformation of the
      underlying multidimensional probability distributions. We apply this algorithm to
      the real-world problem of fully automated voxel-based multispectral image
      segmentation, employing magnetic resonance data sets of the human brain. In
      contrast to previous segmentation approaches, the knowledge obtained within the
      segmentation procedure of a single prototypical reference data set can be re
      utilized for the segmentation of new, 'similar' data employing a strategy of
      incremental adaptive learning based on the DM algorithm. Thus, we obtain a fully
      automatic segmentation method that does neither require manual contour tracing of
      training regions, visual classification of voxel clusters, nor any other kind of
      human intervention. Our application demonstrates that flexible learning by a
      strategy of self-organized incremental model adaptation can contribute to
      increase the efficiency and practicability of biomedical image processing
      systems.

PMID- 15555870
TI  - Early lexical development in a self-organizing neural network.
AB  - In this paper we present a self-organizing neural network model of early lexical
      development called DevLex. The network consists of two self-organizing maps (a
      growing semantic map and a growing phonological map) that are connected via
      associative links trained by Hebbian learning. The model captures a number of
      important phenomena that occur in early lexical acquisition by children, as it
      allows for the representation of a dynamically changing linguistic environment in
      language learning. In our simulations, DevLex develops topographically organized
      representations for linguistic categories over time, models lexical confusion as
      a function of word density and semantic similarity, and shows age-of-acquisition
      effects in the course of learning a growing lexicon. These results match up with
      patterns from empirical research on lexical development, and have significant
      implications for models of language acquisition based on self-organizing neural
      networks.

PMID- 15555871
TI  - Roles of visual experience and intrinsic mechanism in the activity-dependent self
      organization of orientation maps: theory and experiment.
AB  - It is widely accepted that functional maps in the mammalian visual cortex such as
      ocular dominance columns and orientation columns are formed depending on neural
      activity. There is still, however, controversy on how much visual experience
      contributes to the map formation during development. In the present study, we
      address this issue from mathematical modeling and experimental investigation.
      Using a model of activity-dependent self-organization of geniculo-cortical
      afferent inputs, we showed that spontaneous activity in the LGN can produce
      orientation maps, while the exposure to drifting gratings results in sharply
      segregated orientation maps as observed in cat visual cortex. The restricted
      exposure to a single orientation of the grating led to the over-representation of
      the exposed orientation, which was moderated by the contribution of learning
      based on the spontaneous activity. These theoretical results were confirmed by
      intrinsic optical recordings from area 18 of kittens reared under various visual
      conditions.

PMID- 15555872
TI  - Hierarchical self-organization of minicolumnar receptive fields.
AB  - We study self-organization of receptive fields (RFs) of cortical minicolumns.
      Input driven self-organization is induced by Hebbian synaptic plasticity of
      afferent fibers to model minicolumns based on spiking neurons and background
      oscillations. If input in the form of spike patterns is presented during
      learning, the RFs of minicolumns hierarchically specialize to increasingly small
      groups of similar RFs in a series of nested group subdivisions. In a number of
      experiments we show that the system finds clusters of similar spike patterns,
      that it is capable of evenly cover the input space if the input is continuously
      distributed, and that it extracts basic features from input consisting of
      superpositions of spike patterns. With a continuous version of the bars test we,
      furthermore, demonstrate the system's ability to evenly cover the space of
      extracted basic input features. The hierarchical nature and its flexibility with
      respect to input distinguishes the presented type of self-organization from
      others including similar but non-hierarchical self-organization as discussed in
      [Lucke J., & von der Malsburg, C. (2004). Rapid processing and unsupervised
      learning in a model of the cortical macrocolumn. Neural Computation 16, 501-533].
      The capabilities of the presented system match crucial properties of the
      plasticity of cortical RFs and we suggest it as a model for their hierarchical
      formation.

PMID- 15555873
TI  - Role of efflux mechanisms on fluoroquinolone resistance in Streptococcus
      pneumoniae and Pseudomonas aeruginosa.
AB  - Prokaryotic efflux mechanisms can effectively increase the intrinsic resistance
      of bacteria by actively transporting antibiotics out of cells, thus reducing the
      effective concentration of these agents. The fluoroquinolones, similar to most
      other antimicrobial classes, are susceptible to efflux mechanisms, particularly
      in Gram-negative organisms, such as Pseudomonas aeruginosa. Resistant P.
      aeruginosa clones isolated after fluoroquinolone therapy frequently over express
      at least one of the multiple efflux pump mechanisms found in this organism. Gram
      positive bacteria, such as Streptococcus pneumoniae, also possess efflux
      mechanisms, though their effect on fluoroquinolone resistance seems to be more
      limited and selective. In the future, efflux pump inhibitors may offer effective
      adjunctive therapy to antibiotics for the treatment of difficult infections by
      efflux mutants. In the meantime, appropriate antibiotic selection and optimal
      dosing strategies should aim to eradicate the causative pathogen before a
      resistant efflux mutant can emerge.

PMID- 15555874
TI  - Antimicrobial peptides: premises and promises.
AB  - Antimicrobial peptides (AMPs) are an important component of the natural defences
      of most living organisms against invading pathogens. These are relatively small
      (< 10kDa), cationic and amphipathic peptides of variable length, sequence and
      structure. During the past two decades several AMPs have been isolated from a
      wide variety of animals, both vertebrates and invertebrates, and plants as well
      as from bacteria and fungi. Most of these peptides are obtained from different
      sources like macrophages, neutrophils, epithelial cells, haemocytes, fat body,
      reproductive tract, etc. These peptides exhibit broad-spectrum activity against a
      wide range of microorganisms including Gram-positive and Gram-negative bacteria,
      protozoa, yeast, fungi and viruses. A few peptides have also been found to be
      cytotoxic to sperm and tumour cells. AMPs are classified based on the three
      dimensional structural studies carried out with the help of NMR. The peptides are
      broadly classified into five major groups namely (a) peptides that form alpha
      helical structures, (b) peptides rich in cysteine residues, (c) peptides that
      form beta-sheet, (d) peptides rich in regular amino acids namely histatin,
      arginine and proline and (e) peptides composed of rare and modified amino acids.
      Most of these peptides are believed to act by disrupting the plasma membrane
      leading to the lysis of the cell. AMPs have been found to be excellent candidates
      for developing novel antimicrobial agents and a few of these peptides show
      antimicrobial activity against pathogens causing sexually transmitted infection
      (STI), including HIV/HSV. Peptides, namely magainin and nisin have been shown to
      demonstrate contraceptive properties in vitro and in vivo. A few peptides have
      already entered clinical trials for the treatment of impetigo, diabetic foot
      ulcers and gastric helicobacter infections. In this review, we discuss the
      source, structures and mode of action with special reference to therapeutic
      considerations of various AMPs.

PMID- 15555875
TI  - Keeping nanobacterial infections at bay during space travel.
AB  - In January 2004, President George W. Bush unveiled plans to send astronauts to
      the Moon in 2015 and shortly thereafter to Mars. With the prospect of manned
      exploration of the planets drawing ever closer, the new discipline of Space
      Medicine is destined to come to the fore. Moreover, investigations of how human
      beings function under space conditions could provide important new insights into
      fundamental questions of human physiology and disease. We draw attention here to
      one such instance of a disease process that can be provoked by extended periods
      of exposure to low gravity.

PMID- 15555876
TI  - Efficacy of long-term macrolide antibiotic therapy in patients with diffuse
      panbronchiolitis: comparison between HLA-B54-positive and -negative cases.
AB  - This study compared the clinical characteristics and the effects of long-term
      macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients
      with diffuse panbronchiolitis (DPB). Thirty-two Japanese patients were enrolled
      who had the clinical criteria for DPB. All patients received long-term macrolide
      therapy, and therapeutic results were compared according to the presence or the
      absence of HLA-B54 antigen. Clinical, laboratory, radiological and bacterial
      features were strikingly similar in both groups before macrolide therapy. Long
      term treatment with macrolides improved clinical symptoms, PaO(2), and forced
      expiratory volume in 1s (FEV(1)) equally in both groups. This study indicates
      that genetic susceptibility may not explain the pathogenesis of DPB, and that low
      dose macrolide therapy can achieve clinical improvement irrespective of genetic
      predisposition in DPB.

PMID- 15555877
TI  - Inhibition of ampicillin-induced emergence of resistance in intestinal coliforms
      by targeted recombinant beta-lactamase.
AB  - The aim of the present study was to determine whether oral targeted recombinant
      beta-lactamase (TRBL) administration could overcome the development of ampicillin
      induced resistance in the gut microbiota. Eighteen laboratory beagles with
      permanent jejunal fistula were randomised to receive ampicillin + placebo,
      ampicillin + TRBL or placebo. A total of 982 coliform isolates, collected from
      jejunal and faecal samples before, during and after the treatment were tested
      against nine antimicrobials. The proportion of ampicillin resistance (multi
      resistance) among coliform isolates increased from 20 to 36% in the ampicillin +
      placebo group but far less, 20-36%, in the ampicillin + TRBL group. These results
      indicate that TRBL may prevent the emergence of beta-lactam-associated resistance
      in coliforms in the gut.

PMID- 15555878
TI  - Risk factors and mortality associated with Clostridium difficile-associated
      diarrhoea at a VA hospital.
AB  - The objective of this study was to evaluate the risk of certain patient co
      morbidities and antibiotics in the development of Clostridium difficile
      associated diarrhoea (CDAD). Hospitalized patients developing CDAD during a
      specified period were compared with a cohort of patients, matched by age, without
      a diagnosis of CDAD, who were hospitalized during the same time period. Data
      collection included demographics, hospital ward, co-morbid conditions,
      antibiotics received, and mortality. Gender and age were similar in both groups.
      Co-morbid conditions significantly associated with the case group included cancer
      and COPD. The most commonly prescribed antibiotics in the case versus control
      group included levofloxacin, intravenous vancomycin, clindamycin, and
      piperacillin/tazobactam. The case group was associated with a higher mortality
      rate.

PMID- 15555879
TI  - Antimicrobial activity of tigecycline (GAR-936) tested against 3498 recent
      isolates of Staphylococcus aureus recovered from nosocomial and community
      acquired infections.
AB  - Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has
      demonstrated activity against a variety of Gram-positive and -negative bacterial
      pathogens. In vitro activity of tigecycline and comparator agents was determined
      for 3498 recent (2000-2003) strains of Staphylococcus aureus recovered from
      patients with either nosocomial or community-acquired infections. Oxacillin
      susceptible and -resistant S. aureus from both patient populations displayed
      identical results for tigecycline (MIC(50) and MIC(90) results at 0.25 and 0.5
      mg/L, respectively) and all strains were inhibited by 1 mg/L or less. While co
      resistances to other antimicrobial classes were present in oxacillin-resistant
      strains, susceptibility to tigecycline remained unaffected, making the compound
      an attractive candidate for treatment of serious hospital as well as community
      acquired staphylococcal infections.

PMID- 15555880
TI  - Comparison of E-test and disk diffusion assay to evaluate resistance of
      Helicobacter pylori isolates to amoxicillin, clarithromycin, metronidazole and
      tetracycline in Costa Rica.
AB  - MIC distribution and susceptibility to four antimicrobial agents were determined
      by E-test for 94 Helicobacter pylori isolates from Costa Rica. Disk diffusion was
      evaluated as an alternative method to determine susceptibility and compared with
      the E-test results by linear regression analysis and an error-rate bounded
      method. Thirty-eight (40.4%) of the isolates were resistant to metronidazole,
      5.3% to clarithromycin and 5.3% to amoxicillin. No isolate was resistant to
      tetracycline. Multiple resistance was found in 4.3% of the isolates. H. pylori
      isolates were categorised as resistant to amoxicillin, clarithromycin and
      tetracycline when inhibition diameters were less than 25, 21 and 25 mm,
      respectively, in the disk diffusion assay. A breakpoint diameter for
      metronidazole with disk diffusion could not be firmly established.

PMID- 15555881
TI  - Porphyrin-based compounds exert antibacterial action against the sexually
      transmitted pathogens Neisseria gonorrhoeae and Haemophilus ducreyi.
AB  - A series of porphyrin based compounds without (nMP) or with (MP) metals were
      found to have potent bactericidal action in vitro against the sexually
      transmitted pathogens Neisseria gonorrhoeae and Haemophilus ducreyi. nMP and MP
      did not show bactericidal activity against five species of lactobacilli. An MP
      containing gallium had the capacity to block a gonococcal infection in a murine
      vaginal model, indicating that its development as a topical microbicide to block
      sexually transmitted bacterial infections is warranted. In contrast to other
      bacterial species, loss of the gonococcal haemoglobin uptake system encoded by
      hpuB or energy supplied through the TonB-ExbB-ExbD system did not significantly
      affect levels of MP-susceptibility in gonococci. In contrast, mutations in
      gonococci that inactivate the mtrCDE-encoded efflux pump were found to enhance
      gonococcal susceptibility to nMPs and MPs while over-production of this efflux
      pump decreased levels of gonococcal susceptibility to these compounds.

PMID- 15555882
TI  - Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more
      than 5000 European Enterobacteriaceae isolates.
AB  - In vitro susceptibility to 15 beta-lactam antibiotics was evaluated using
      Enterobacteriaceae isolated during the SENTRY Antimicrobial Surveillance Program.
      Piperacillin/tazobactam was the most active penicillin against Escherichia coli,
      Proteus mirabilis, Klebsiella oxytoca and Klebsiella pneumoniae (94.9%, 98.3%,
      87.4% and 82.9% of isolates susceptible). Of the cephalosporins, cefepime was
      most effective against Escherichia coli, Proteus mirabilis and Enterobacter
      cloacae (99.2%, 96.3% and 95.2% of isolates susceptible, respectively) and
      cefoxitin against Klebsiella oxytoca and Klebsiella pneumoniae (98.6% and 95.6%
      of isolates susceptible). Carbapenems had excellent activity (> or =99.5% of all
      isolates). ESBL-production was confirmed with the ESBL-Etest and disk diffusion
      test in 1.3% of Escherichia coli isolates, 18.4% of Klebsiella pneumoniae, 12.6%
      of Klebsiella oxytoca and 5.3% of Proteus mirabilis isolates.

PMID- 15555883
TI  - A seven-year survey of susceptibility to marbofloxacin of pathogenic strains
      isolated from pets.
AB  - This study, Vetoquinol S.A. epidemiosurveillance, was conducted from 1994 to 2001
      in order to determine the susceptibility (by MIC determination) to marbofloxacin
      (a third generation fluoroquinolone used only in individual administration for
      animals). Strains from infected pets originated from six European countries.
      Isolates were collected from urinary infections (Escherichia coli), respiratory
      infections (Pasteurella multocida), dermatological infections (Staphylococcus
      intermedius, Pseudomonas aeruginosa) and otitis (S. intermedius, P. aeruginosa).
      The MIC distribution for each species was the same both before and after the
      launch of marbofloxacin in 1995. In E. coli, a resistant population was present
      before the use of marbofloxacin; this resistance was induced by co- or cross
      resistance to other antibiotics used previously. Over this period, there was no
      significant evolution of MIC(90) for any bacterial species studied and no
      development of resistance was observed. Marbofloxacin was the most active
      antibiotic against P. multocida isolates and had the lowest MIC. No difference in
      MIC distribution was seen between the S. intermedius (unimodal distribution)
      isolated from dermatological infections and those from otitis. This was also true
      for P. aeruginosa. The use of marbofloxacin was not found to have induced a
      significant increase or spread of resistant bacteria.

PMID- 15555884
TI  - Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle
      encapsulated antitubercular drugs at sub-therapeutic dose against experimental
      tuberculosis.
AB  - The present study was designed to evaluate the chemotherapeutic efficacy of poly
      (DL-lactide-co-glycolide) (PLG) nanoparticles (NP) encapsulating three front-line
      antitubercular drugs (ATDs: rifampicin, RIF; isoniazid, INH and pyrazinamide,
      PZA) at 2/3rd therapeutic dose. PLG nanoparticles prepared by the double emulsion
      and solvent evaporation technique were administered orally at 2/3rd therapeutic
      dose to guinea pigs. A single oral administration of the formulation resulted in
      sustained drug levels in the plasma for 7-12 days and in the organs for 11-14
      days with a significant improvement in mean residence time as well as drug
      bioavailability. The administration of PLG nanoparticles every 10 days (five
      doses) to Mycobacterium tuberculosis H(37)Rv infected guinea pigs led to
      undetectable bacilli in the organs, as did 46 conventional doses. Therefore,
      nanoparticle based antitubercular chemotherapy forms a sound basis for a
      reduction in dosing frequency and also offers the possibility of reducing the
      drug dosage.

PMID- 15555885
TI  - Resistance development in community-acquired strains of methicillin-resistant
      Staphylococcus aureus: an in vitro study.
AB  - This study compares in vitro antimicrobial resistance development between strains
      of Staphylococcus aureus including newly described community-acquired methicillin
      resistant strains (CA-MRSA). High-level resistance developed in all strains of S.
      aureus after exposure to rifampicin and gentamicin and in some strains after
      fusidic acid exposure, independent of methicillin resistance phenotype.
      Resistance did not develop after exposure to clindamycin, cotrimoxazole,
      ciprofloxacin, linezolid, or vancomycin. These results have important
      implications for therapy of CA-MRSA infections.

PMID- 15555886
TI  - Efficacy of the latest fluoroquinolones against experimental Yersinia pestis.
AB  - The efficacies of prophylactic and therapeutic gatifloxacin and moxifloxacin were
      assessed in a BALB/c mouse model of systemic and pneumonic plague and compared
      with ciprofloxacin. Mice were given 100 mg/kg of the antibiotic by oral
      administration twice daily for 7 days starting 1h prior to infection or following
      infection. All antibiotics offered full protection for up to 6h following
      systemic challenge, and for up to 30 h following an aerosol challenge. The
      efficacy of each of the antibiotics decreased when antibiotics were started 18 h
      following systemic challenge and 48 h following aerosol challenge.
      Fluoroquinolones may therefore be considered useful candidates for the treatment
      of bubonic and pneumonic plague.

PMID- 15555887
TI  - In vitro antibacterial activity of echinomycin and a novel analogue, YK2000,
      against vancomycin-resistant enterococci.
AB  - The in vitro inhibitory and bactericidal activity of echinomycin and its the
      novel synthetic analogues of echinomycin,YK2000 and YK2005, were evaluated using
      93 clinical isolates of vancomycin-resistant enterococci (VRE). In agar dilution
      tests, the MIC(90) of echinomycin and YK2000 were 0.125 and 8 mg/l, respectively,
      using Mueller-Hinton II agar, while that of YK2005 was 32 mg/l. Bactericidal
      activity of echinomycin and YK2000 were two to four times higher than the MIC in
      time-kill assay experiments. These results suggest that echinomycin and its
      analogues might be useful as anti-VRE drugs.

PMID- 15555888
TI  - Activity of telithromycin against erythromycin-susceptible and -resistant
      Streptococcus pneumoniae isolates from adults with invasive infections.
AB  - A telithromycin (TEL) kill-kinetics study was conducted with 120 clinically
      significant Streptococcus pneumoniae isolates (60 susceptible and 60 highly
      resistant to erythromycin). Time-kill curves were performed using different
      antibiotic concentrations. The minimum inhibitory concentrations (MICs) of TEL
      were low for both erythromycin-susceptible (MIC < or = 0.016 mg/L) and
      erythromycin-resistant strains (MIC < or = 0.25 mg/L). TEL showed 99.9% killing
      of all erythromycin resistant strains at 18-24 h of incubation. Even for strains
      with erythromycin MICs > or = 64.0 mg/L, TEL was uniformly bactericidal at 0.25
      mg/L.

PMID- 15555889
TI  - Resistance determinants in strains of Clostridium difficile from two
      geographically distinct populations.
AB  - Ninety-three clinical isolates of Clostridium difficile, comprising 65 from Royal
      Gwent Hospital, Newport and 28 from Southmead Hospital, Bristol were examined to
      determine the prevalence of genes coding for macrolide resistance and to explore
      differences in susceptibility patterns. Antibiogram testing produced similar
      results for both sets of strains with respect to amoxicillin, tetracycline,
      erythromycin and cefotaxime. Results differed for rifampicin, where 53% of the
      Bristol isolates were resistant, compared with 3% of the Newport isolates.
      Clindamycin disc susceptibility testing produced similar resistance rates.
      However, clindamycin MIC determinations revealed that 53% of the Bristol strains
      exhibited high-level resistance (MIC > 256 mg/L), whereas strains from Newport
      had clindamycin MICs ranging from 0.25 to 3mg/L. erm (B) was present in 15 of the
      strains from Bristol and in none of the Newport strains. erm (F) and erm (Q) were
      not detected in either population. The two geographically distinct populations of
      C. difficile differed considerably in their susceptibility to antibiotics. The
      possibility that C. difficile may serve as a conservator for resistant
      determinants subsequent to exposure to antimicrobial agents, has important
      implications for infection control.

PMID- 15555890
TI  - Only percentage within species; neither incidence, nor prevalence: demographic
      information and representative surveillance data are urgently needed to estimate
      the burden of antimicrobial resistance.

PMID- 15555892
TI  - Lower gastrointestinal bleeding in a patient with typhoid fever.

PMID- 15555893
TI  - First isolation of a CTX-M-3 beta-lactamase producer in the United Kingdom.

PMID- 15555894
TI  - Trends in antifungal use and species distribution among Candida isolates in a
      large paediatric hospital.

PMID- 15555895
TI  - Treatment with linezolid and rifampicin for 18 months for recurrent infection of
      a megaprosthesis in a patient with Ewing's sarcoma.

PMID- 15555896
TI  - Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya
      phosphatidylcholine.
AB  - The encapsulation of acid (AD) and sodium diclofenac (SD) in small unilamellar
      liposomes (SUV) as well as the interactions of the drug with the bilayer was
      studied. SUV was prepared by sonication from multilamellar liposomes containing
      soya phosphatidylcholine and diclofenac at various proportions. The size
      distribution obtained from dynamic light scattering showed that the incorporation
      of SD decreases significantly the size of the liposomes suggesting that the drug
      interacts with the bilayer of the liposomes. This size decrease is related with
      the phase transition of liposomes to mixed micelar solution. The encapsulation of
      the hydrophilic dye indocyanine green in the aqueous compartment of liposomes
      showed that the rate of captured dye decreases with SD concentration suggesting
      the transition of liposomes to mixed micelles. The (31)P NMR analysis indicates
      that SD interacts with the phosphate of phosphatidylcholine head groups. A
      schematic model for interaction of SD with phosphatidylcholine of the liposomes
      in which the diclofenac anion interacts with the ammonium group of the
      phospholipid and the dichlorophenyl ring occupies a more internal site of bilayer
      near phosphate group was proposed.

PMID- 15555897
TI  - Preparation of stable aqueous suspension of a hydrophobic drug with polymers.
AB  - Pharmaceutical preparation of a hydrophobic aldose reductase inhibitor 5-(3
      ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) was investigated. CT112
      dissolved in a basic solution with different kinds of polymers was neutralized by
      acid to obtain a suspension preparation. In particular, the addition of a
      polymer, hydroxypropyl methyl cellulose (HPMC) provided a stable CT112 suspension
      with a homogeneous particle size, and there seemed to be an optimal concentration
      of HPMC for the stable suspension. The addition of polysorbate 80 brought higher
      CT112 solubility in water, but did not provide a stable suspension. X-ray
      diffraction, IR spectrum, and thermal analysis revealed that the particles in the
      suspension with HPMC had lower degree of crystallinity, less hydrophobic particle
      surface, and lower melting point and decreased fusion enthalpy than the
      suspension without HPMC. These results suggested that the highly stable CT112
      suspension could be attained by the adsorption of the polymer.

PMID- 15555898
TI  - Polymerizable ion-pair amphiphile that has a polymerizable group at cationic
      ammonium chain.
AB  - Polymerizable ion-pair amphiphile (PIPA) that has a polymerizable lipoyl group on
      cationic ammonium chain was prepared to compare the advantage of ion-pair form
      with the conventional polymerizable ammonium surfactant in the points of
      stability of vesicle and permeation properties. PIPA introduced in this paper,
      compared to previously reported one with polymerizable group on anionic chain
      side, showed similar vesicle stability in addition to high encapsulation
      efficiency and resistance to disruption by SDS or Triton X-100. Reasons for such
      high encapsulation and low permeability of the PIPA vesicle are investigated and
      the possible applications are briefly discussed.

PMID- 15555899
TI  - The estimation of the hydrophobic and electrostatic contributions to the free
      energy change upon cationic surfactants binding to Jack bean urease.
AB  - The binding of a homologous series of n-alkyltrimethyl ammonium bromides with
      Jack bean urease (JBU) have been studied previously. It has been suggested that
      both electrostatic and hydrophobic interactions are involved in the formation of
      surfactant-protein complexes, but there is not any quantities analyzing method
      for resolution of their contributions in the process. In the present study, at
      first, the intrinsic Gibbs free energy of binding, DeltaG(b,nu), has been
      calculated for these systems and the trend of variation for both binding sets
      have been interpreted on basis of cooperativity and hydrophobicity of
      surfactants. Subsequently, a novel approach has been introduced for estimation of
      electrostatic and hydrophobic interactions in DeltaG(b,nu), by considering of
      this fact that DeltaG(b,nu) is the summation of electrostatic, DeltaG(b,nu)(ele),
      and hydrophobic, DeltaG(b,nu)(hyd), parts and considering this fact that just
      DeltaG(b,nu)(hyd) is a function of hydrocarbon tail length of surfactant (C(n)).
      The results represents the higher positive rule of electrostatic interactions in
      binding affinity of first set and inhibiting rule of this interaction in the
      second binding set. The predominate driving force in the second binding set is
      entropy statistical effect, which arises from numerous number of binding sites in
      this set. A binding mechanism on basis of structural changes in JBU due to its
      interaction with cationic surfactants has also been proposed.

PMID- 15555900
TI  - Nanomanipulation of extended single-DNA molecules on modified mica surfaces using
      the atomic force microscopy.
AB  - The technique of nanometer scale manipulation is very important in constructing
      nano-structures and nano-devices. By using atomic force microscope, three kinds
      of controllable manipulation on single-DNA molecules were introduced in the
      paper. DNA molecules deposited and extended on modified mica surface were first
      imaged by tapping mode, then cutting, bending, and pushing were respectively
      performed on single-DNA molecules. The results of the manipulation depend on the
      interaction between tip and DNA as well as between substrate and DNA.

PMID- 15555901
TI  - The influence of hydroxyapatite modification on the cross-linking of
      polydimethylsiloxane/HAp composites.
AB  - Hydroxyapatite (HAp) was modified by the action of various hydrophobic agents
      based on silicon-containing compounds. The influence of the type of applied agent
      on the thermodynamic and kinetic parameters of the cross-linking of poly(dimethyl
      siloxane)/HAp composites was investigated. All the modified HAp particles became
      hydrophobic and these samples were used to synthesize the
      polysiloxane/hydroxyapatite composites (PDMS/HAp). The possible modes of
      interaction between the hydroxyapatite and hydrophobing agents were discussed.
      The most probable interaction between hydroxyapatite and the applied hydrophobing
      agents is hydrogen bonding. PDMS/HAp composites were formed directly in the cell
      of the DSC and cross-linking was investigated in situ. It was determined that the
      introduction of hydroxyapatite into polysiloxane matrices changed the enthalpy of
      cross-linking, as well as the activation energy of cross-linking and reaction
      order, while the introduction of modified HAp led to thermodynamic and kinetic
      parameters more similar to those of the cross-linking of unfilled elastomer.

PMID- 15555902
TI  - Effect of pulverization on hydration kinetic behaviors of creatine anhydrate
      powders.
AB  - The crystal orientation of creatine monohydrate varies significantly with
      tableting performance and pulverizing mechanism. Furthermore, the X-ray
      diffraction patterns of anhydrous forms of untreated creatine monohydrate and of
      pulverized creatine monohydrate exhibit different crystal orientations. However,
      hygroscopic forms of unpulverized creatine anhydrate and pulverized creatine
      anhydrate was exhibit the same diffraction peak pattern. The hygroscopicity of
      unpulverized and pulverized creatine anhydrate has been investigated by hydration
      kinetic methods using isothermal differential scanning calorimetry data. Testing
      of the hygroscopicity of unpulverized and pulverized creatine anhydrate at
      various levels of relative humidity (RH) at 25 degrees C revealed that the
      anhydrate was stable at less than 33% RH, but was transformed into the
      monohydrate at more than 52% RH. Hydration data of unpulverized and pulverized
      creatine anhydrate at 60% and 75% RH were calculated to determine hydration
      kinetics using various solid-state kinetic models. The hydration type of
      unpulverized and pulverized creatine anhydrate powder follows the zero-order
      mechanism (Polany-Winger equation) R1. The transition rate constant of pulverized
      creatine anhydrate, calculated from the slope of the straight line, was about
      1.34-1.36 times higher than that of unpulverized creatine anhydrate.

PMID- 15555903
TI  - Characterization of the surface properties of xylan by FT-Raman spectroscopy and
      wicking technique.
AB  - Using FT-Raman spectroscopy, column wicking technique and the equations of
      Washburn as well as van Oss et al., the surface properties of xylan, the main
      component in hemicelluloses, has been characterized and estimated. Raman spectrum
      showed that xylan has been structured by acetyl group and methyl-bonded glucurono
      group. Obtained results show that the surface free energy of xylan is higher in
      comparison with literature reported values for cellulose because the former has a
      larger Lifshitz-van der Waals component than the latter. However, xylan has been
      found to have very smaller polarity and orientation data than that of cellulose.

PMID- 15555904
TI  - Surface free energy and bacterial retention to saliva-coated dental implant
      materials--an in vitro study.
AB  - The aim of the present investigation was to compare the in vitro bacterial
      retention on saliva-coated implant materials (pure titanium grade 2 (cp-Ti) and a
      titanium alloy (Ti-6Al-4V) surfaces), presenting similar surface roughness, and
      to assess the influence of physico-chemical surface properties of bacterial
      strain and implant materials on in vitro bacterial adherence. Two bacterial
      strains (one hydrophilic strain and one hydrophobic strain) were used and the
      following were evaluated: bacterial cell adherence, SFE values as well as the
      Lifshitz-van-der Waals, the Lewis acid base components of SFE, the interfacial
      free energy and the non-dispersive interactions according to two complementary
      contact angle measurement methods: the sessile drop method and the captive bubble
      method. Our results showed similar patterns of adherent bacterial cells on saliva
      coated cp-Ti and saliva-coated Ti-6Al-4V. These findings could suggest that
      bacterial colonization (i.e. plaque formation) is similar on saliva-coated cp-Ti
      and Ti-6Al-4V surfaces and indicate that both materials could be suitable for use
      as transgingival abutment or healing implant components. The same physico
      chemical properties exhibited by saliva-coated cp-Ti and TA6V, as shown by the
      sessile drop method and the captive bubble method, could explain this similar
      bacterial colonisation. Therefore, higher values of total surface free energy of
      saliva-coated cp-Ti and saliva-coated TA6V samples (gamma(SV) approximately
      65mJ/m(2)) were reported using the captive bubble method indicating a less
      hydrophobic character of these surfaces than with the sessile drop method
      (gamma(S) approximately 44.50mJ/m(2)) and consequently possible differences in
      oral bacterial retention according the theory described by Absolom et al. The
      number of adherent hydrophobic S. sanguinis cells was two-fold higher than that
      of hydrophilic S. constellatus cells. Our results confirm that physico-chemical
      surface properties of oral bacterial strains play a role in bacterial retention
      to implant materials in the presence of adsorbed salivary proteins.

PMID- 15555905
TI  - Significance of progesterone receptor-A and -B expressions in endometrial
      adenocarcinoma.
AB  - The progesterone receptor (PR) has two isoforms, A and B, among which PR-B is
      mainly involved in regulating proliferation of the uterine endometrium. In this
      study, immunohistochemical analysis was carried out to investigate the
      correlation of PR-A and -B expressions with cell cycle-regulatory proteins and
      clinicopathological parameters in endometrial adenocarcinoma. One hundred and
      forty-one endometrioid adenocarcinomas [76 with well-differentiated (G1), 35 with
      moderately differentiated (G2) and 30 with poorly differentiated (G3)] were used.
      Specimens of formalin-fixed and paraffin-embedded tissue were
      immunohistochemically stained using the high polymer method (HISTOFINE,
      NICHIREI). The percentage of positive nuclei of tumor cells observed in three
      high power fields was expressed as a labeling index (LI). PR-B expression
      significantly occurred more frequently in G1. It was inversely correlated with
      p53 gene mutation and p53 over expression, and also with clinicopathological
      variables, including myometrial and lymph-vascular space invasion and the FIGO
      stage. Patients with negative PR-B had a poorer prognosis than positive cases. PR
      A expression was also significantly higher in G1 and was inversely correlated
      with Ki-67 expression and myometrial invasion, but not with prognosis. PR-A and 
      B expressions were significantly correlated with biologically malignant
      potential. Especially, PR-B expression is useful as a prognostic indicator of
      endometrial adenocarcinoma.

PMID- 15555906
TI  - The cationic charges on Arg347, Arg358 and Arg449 of human cytochrome P450c17
      (CYP17) are essential for the enzyme's cytochrome b5-dependent acyl-carbon
      cleavage activities.
AB  - CYP17 (17alpha-hydroxylase-17,20-lyase; also P450c17 or P450(17alpha)) catalyses
      the17alpha-hydroxylation of progestogens and the subsequent acyl-carbon cleavage
      of the 17alpha-hydroxylated products (lyase activity) in the biosynthesis of
      androgens. The enzyme also catalyses another type of acyl-carbon cleavage (direct
      cleavage activity) in which the 17alpha-hydroxylation reaction is by-passed.
      Human CYP17 is heavily dependent on the presence of the membrane form of
      cytochrome b(5) for both its lyase and direct cleavage activities. In the present
      study it was found that substitution of human CYP17 amino acids, Arg(347),
      Arg(358) and Arg(449), with non-cationic residues, yielded variants that were
      impaired in the two acyl-carbon bond cleavage activities, quantitatively to the
      same extent and these were reduced to between 3 and 4% of the wild-type protein.
      When the arginines were replaced by lysines, the sensitivity to cytochrome b(5)
      was restored and the acyl-carbon cleavage activities were recovered. All of the
      human mutant CYP17 proteins displayed wild-type hydroxylase activity, in the
      absence of cytochrome b(5). The results suggest that the bifurcated cationic
      charges at Arg(347), Arg(358) and Arg(449) make important contributions to the
      formation of catalytically competent CYP17.cytochrome b(5) complex. The results
      support our original proposal that the main role of cytochrome b(5) is to promote
      protein conformational changes which allow the iron-peroxo anion to form a
      tetrahedral adduct that fragments to produce the acyl-carbon cleavage products.

PMID- 15555907
TI  - Molecular activity of 1,25-dihydroxyvitamin D3 in primary cultures of human
      prostatic epithelial cells revealed by cDNA microarray analysis.
AB  - 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] exerts anti-proliferative,
      differentiating and apoptotic effects on prostatic cells. These activities, in
      addition to epidemiologic findings that link Vitamin D to prostate cancer risk,
      support the use of 1,25(OH)(2)D(3) for prevention or therapy of prostate cancer.
      The molecular mechanisms by which 1,25(OH)(2)D(3) exerts antitumor effects on
      prostatic cells are not well-defined. In addition, there is heterogeneity among
      the responses of various prostate cell lines and primary cultures to
      1,25(OH)(2)D(3) with regard to growth inhibition, differentiation and apoptosis.
      To understand the basis of these differential responses and to develop a better
      model of Vitamin D action in the prostate, we performed cDNA microarray analyses
      of primary cultures of normal and malignant human prostatic epithelial cells,
      treated with 50 nM of 1,25(OH)(2)D(3) for 6 and 24 h. CYP24 (25-hydroxyvitamin
      D(3)-24-hydroxylase) was the most highly upregulated gene. Significant and early
      upregulation of dual specificity phosphatase 10 (DUSP10), validated in five
      additional primary cultures, points to inhibition of members of the mitogen
      activated protein kinase (MAPK) superfamily as a key event mediating activity of
      1,25(OH)(2)D(3) in prostatic epithelial cells. The functions of other regulated
      genes suggest protection by 1,25(OH)(2)D(3) from oxidative stress. Overall, these
      results provide new insights into the molecular basis of antitumor activities of
      Vitamin D in prostate cells.

PMID- 15555908
TI  - The genes encoding the hydroxylase of 3-hydroxy-9,10-secoandrosta-1,3,5(10)
      triene-9,17-dione in steroid degradation in Comamonas testosteroni TA441.
AB  - Steroid degradation genes of Comamonas testosteroni TA441 are encoded in at least
      two gene clusters: one containing the meta-cleavage enzyme gene tesB; and another
      consisting of ORF18, 17, tesI, H, ORF11, 12, and tesDEFG. TesH and I are,
      respectively, the Delta(1)- and Delta(4)(5alpha)-dehydrogenase of the 3
      ketosteroid, TesD is the hydrolase for the product of meta-cleavage reaction, and
      TesEFG degrade one of the product of TesD. In this report, we describe the
      identification of the function of ORF11 (tesA2) and 12 (tesA1). The TesA1- and
      TesA2-disrupted mutant accumulated two characteristic intermediate compounds,
      which were identified as 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione
      (3-HSA) and its hydroxylated derivative, 3,17-dihydroxy-9,10-secoandrosta
      1,3,5(10)-triene-9,17-dione by MS and NMR analysis. A complementation experiment
      using a broad-host range plasmid showed that both TesA1 and A2 are necessary for
      hydroxylation of 3-HSA to 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17
      dione (3,4-DHSA).

PMID- 15555909
TI  - Potent CYP17 inhibitors: improved syntheses, pharmacokinetics and anti-tumor
      activity in the LNCaP human prostate cancer model.
AB  - A facile preparation of azolyl steroids, VN/85-1 and VN/87-1 (potent inhibitors
      of CYP17) has been developed. This process without tedious chromatographic
      separations improved the overall yields from 55 and 45% to 70 and 65% for VN/85-1
      and VN/87-1, respectively. Pharmacokinetic studies of VN/85-1 were conducted in
      male SCID mice. Following subcutaneous (s.c.) administration of 100mg/kg of VN/85
      1, peak plasma level of 16.73 microg/ml occurred after 45 min, and the compound
      was cleared rapidly with a t(1/2) of 52.34 min. The bioavailability of VN/85-1
      after s.c. administration was 83.0%. VN/85-1 was also rapidly metabolized to the
      corresponding 3-oxo-4-ene analog, 17-(1H-imidazol-1-yl)androsta-4,16-diene-3-one
      (VN/108-1). In our attempt to optimize the anti-tumor efficacy of these two CYP17
      inhibitors, we studied their anti-tumor efficacies in male SCID mice bearing
      LNCaP tumor xenografts, utilizing various drug doses and drug scheduling. Three
      times a day dose regimen (3 x dose regimen) of VN/85-1 was more effective than a
      once daily dose. In contrast, 3 x dose regimen doses of VN/87-1 were less
      effective than the once daily dose. However, at their effective dosage regimes,
      VN/85-1 and VN/87-1 were each as effective as castration and more effective than
      finasteride or casodex, an anti-androgen used for prostate cancer (PC) therapy.
      For all of the treatments, there was a strong correlation between the tumor
      volumes and other associated parameters, such as, tumor weights, and serum
      testosterone (T) and PSA levels. These results indicate that VN/85-1 or VN/87-1
      may be useful in the treatment of hormone-dependent prostate cancer.

PMID- 15555910
TI  - Mammary steroid metabolizing enzymes in relation to hyperplasia and tumorigenesis
      in the dog.
AB  - Progesterone and estradiol play a crucial role in the control of mammary gland
      proliferation and tumour formation in the dog. However, little is known whether
      steroid metabolizing enzymes are present within the canine mammary gland that may
      play a modulating role in the bioavailability of progesterone and estrogen. In
      this study we investigated the expression of the steroid metabolizing enzymes
      5alpha-reductase (type I and type II) and aromatase in relation to hyperplasia or
      tumorigenesis in the canine mammary tissue. The relative mRNA concentrations were
      examined by a semi-quantitative reverse-transcriptase PCR analysis (RT-PCR). In
      addition the affinity of dihydroprogesterone (5alpha-reduced metabolite of
      progesterone) for canine progesterone receptors was investigated. Quantification
      of the RT-PCR products revealed that in mammary tumours a significantly higher
      expression of aromatase is present in comparison to normal mammary tissue.
      Furthermore, significant decrease in expression of both aromatase and 5alpha
      reductase type II enzymes was found in hyperplasic mammary tissue compared to
      tumours. The changes in expression of type II 5alpha-reductase and aromatase were
      highly correlated. 5alpha-Reduction of progesterone to dihydroprogesterone
      resulted in a six-fold less affinity for the canine progesterone receptor. It is
      concluded that hyperplasia is associated with a decreased expression of type II
      5alpha-reductase and aromatase enzymes, whereas in tumours the opposite situation
      is found.

PMID- 15555911
TI  - Triphasic pattern in the ex vivo response of human proliferative phase
      endometrium to oestrogens.
AB  - The aim of this study was to evaluate the ex vivo oestrogen responsiveness of
      human proliferative phase endometrium using short-term explant cultures. The
      effects of oestrogen (17beta-E2) on proliferation and the expression of oestrogen
      responsive genes known to be involved in regulating endometrial function were
      evaluated. Three distinct response patterns could be distinguished: (1) the
      menstrual (M) phase pattern (cycle days 2-5), which is characterised by a
      complete lack in the proliferative response to 17beta-E2, while an increased
      expression of AR (2.6-fold, P<0.01), PR (2.7-fold, P<0.01) and COX-2 (3.5-fold,
      P<0.01) at the mRNA level was observed and a similar upregulation was also found
      for AR, PR and COX-2 at the protein level; (2) the early proliferative (EP) phase
      pattern (cycle days 6-10) with 17beta-E2 enhanced proliferation in the stroma
      (1.7-fold, P<0.05), whereas the expression of AR, PR and COX-2 were not affected
      at the mRNA and protein levels and ER-alpha mRNA and protein levels were
      significantly reduced by 17beta-E2; (3) the late proliferative (LP) phase pattern
      (cycle days 11-14), which is characterised by a moderate stimulation of
      proliferation (1.4-fold, P<0.05) and PR mRNA expression (1.7-fold, P<0.01) by
      17beta-E2. In conclusion, three distinct response patterns to 17beta-E2 could be
      identified with respect to proliferation and the expression of known oestrogen
      responsive genes in human proliferative phase endometrium explant cultures.

PMID- 15555912
TI  - Characterisation of steroid receptor expression in the human prostate carcinoma
      cell line 22RV1 and quantification of androgen effects on mRNA regulation of
      prostate-specific genes.
AB  - In this study, the effect of natural androgens on the expression of androgen
      regulated genes in the human prostate carcinoma cell line 22RV1 was
      characterised. To clarify the usefulness of the cells for in vitro studies
      concerning activation of androgen responsive genes by various steroidal compounds
      steroid receptor expression patterns had to be characterised intensively.
      Expression of androgen receptor (AR), estrogen receptor alpha (ERalpha) and beta
      (ERbeta), progestin receptor (PR) and glucocorticoid receptor alpha and beta was
      investigated by the means of RT-PCR, immunocytochemistry, ligand binding or
      Western blot. 22RV1 cells were proved to express androgen receptor and less
      glucocorticoid receptor beta on mRNA level. The confirmed mutation of the
      androgen receptor at codon H874 slightly apart from the steroid binding pocket
      seemed not to cause alteration of natural steroid hormone binding. mRNA
      expression of all progestin and estrogen receptor isoforms as well as
      glucocorticoid receptor alpha could not be detected. To study functional
      relevance of above-mentioned findings nine androgen-regulated genes were chosen
      to characterise the cell line and to determine androgenic effects using highly
      sensitive real-time RT-PCR. Addition of the three natural steroids
      dihydrotestosterone (DHT), testosterone, and 19-nortestosterone significantly
      influenced mRNA expression profiles. All compounds under study showed clear time
      dependent and androgen-specific effects on transcriptional level. The results
      demonstrate that the cultivated human prostate carcinoma epithelial cells have a
      hormonal sensitivity correlated with the presence of specific receptors and can,
      therefore, serve as a selective model to study hormone action.

PMID- 15555913
TI  - Steroidogenic activities in MA-10 Leydig cells are differentially altered by cAMP
      and Mullerian inhibiting substance.
AB  - In addition to causing Mullerian duct regression in fetal males, Mullerian
      inhibiting substance (MIS) inhibits the expression of the bifunctional cytochrome
      P450, C17 hydroxylase/C(17-20) lyase (Cyp17), the enzyme that catalyzes the
      committed step in sex steroid synthesis. To investigate the paracrine effects of
      MIS on steroidogenic activity, we have performed assays with microsomes from
      mouse MA-10 Leydig cells. With microsomes from untreated MA-10 cells,
      progesterone was largely metabolized by 5alpha-reductase and subsequently
      converted by 3-keto steroid reductases to allopregnanolone and
      epiallopregnanolone. Addition of cAMP to the cells shifted microsomal steroid
      production to the Cyp17 product androstenedione and its 5alpha,3beta-reduced
      form, epiandrosterone. Microsomes from MIS-treated cells were less active with
      the progesterone substrate than those of untreated cells but co-treatment of the
      cells with both MIS and cAMP mitigated the cAMP-induced shift of the microsomes
      to androstenedione production. Quantitative analyses of steroid production by
      Cyp17 showed that cAMP decreased the amount of 17-hydroxyprogesterone produced
      relative to the androstenedione, suggesting that cAMP signaling lowers the
      efficiency of the Cyp17 hydroxylase activity or else increases the efficiency of
      its lyase activity. Addition of MIS to the cAMP-treated cells partially reversed
      this effect, as well. These results indicate that cAMP induces MA-10 cells to
      switch from producing 5alpha-reduced progesterone metabolites to producing
      androstenedione and its metabolites by increasing Cyp17 expression and its
      relative lyase activity, both of which are inhibited by MIS.

PMID- 15555914
TI  - Role of voltage-gated calcium channels in potassium-stimulated aldosterone
      secretion from rat adrenal zona glomerulosa cells.
AB  - The mineralocorticoid aldosterone plays an important role in the regulation of
      plasma electrolyte homeostasis. Exposure of acutely isolated rat adrenal zona
      glomerulosa cells to elevated K(+) activates voltage-gated calcium channels and
      initiates a calcium-dependent increase in aldosterone synthesis. We developed a
      novel 96-well format aldosterone secretion assay to rapidly evaluate the effect
      of known T- and L-type calcium channel antagonists on K(+)-stimulated aldosterone
      secretion and better define the role of voltage-gated calcium channels in this
      process. Reported T-type antagonists, mibefradil and Ni(2+), and selected L-type
      antagonist dihydropyridines, inhibited K(+)-stimulated aldosterone synthesis.
      Dihydropyridine-mediated inhibition occurred at concentrations which had no
      effect on rat alpha1H T-type Ca(2+) currents. In contrast, below 10 microM, the L
      type antagonists verapamil and diltiazem showed only minimal inhibitory effects.
      To examine the selectivity of the calcium channel antagonist-mediated inhibition,
      we established an aldosterone secretion assay in which 8Br-cAMP stimulates
      aldosterone secretion independent of extracellular calcium. Mibefradil remained
      inhibitory in this assay, while the dihydropyridines had only limited effects.
      Taken together, these data demonstrate a role for the L-type calcium channel in
      K(+)-stimulated aldosterone secretion. Further, they confirm the need for
      selective T-type calcium channel antagonists to better address the role of T-type
      channels in K(+)-stimulated aldosterone secretion.

PMID- 15555915
TI  - Molecular physiology and modulation of somatodendritic A-type potassium channels.
AB  - The somatodendritic subthreshold A-type K+ current (ISA) in nerve cells is a
      critical component of the ensemble of voltage-gated ionic currents that determine
      somatodendritic signal integration. The underlying K+ channel belongs to the Shal
      subfamily of voltage-gated K+ channels. Most Shal channels across the animal
      kingdom share a high degree of structural conservation, operate in the
      subthreshold range of membrane potentials, and exhibit relatively fast
      inactivation and recovery from inactivation. Mammalian Shal K+ channels (Kv4)
      undergo preferential closed-state inactivation with features that are generally
      inconsistent with the classical mechanisms of inactivation typical of Shaker K+
      channels. Here, we review (1) the physiological and genetic properties of ISA, 2
      the molecular mechanisms of Kv4 inactivation and its remodeling by a family of
      soluble calcium-binding proteins (KChIPs) and a membrane-bound dipeptidase-like
      protein (DPPX), and (3) the modulation of Kv4 channels by protein
      phosphorylation.

PMID- 15555916
TI  - Peripheral myelin protein 22 kDa and protein zero: domain specific trans
      interactions.
AB  - The peripheral myelin proteins P0 and PMP22 are associated in preparations of
      compact myelin and in cell cultures coexpressing both molecules. The mechanism of
      this interaction, however, still needs to be unravelled. We have established
      three different (cell-cell, cell-protein, protein-protein based) assay systems
      using retrovirally transduced HeLa cells that overexpressed either PMP22 or P0
      and purified GST fusion oligopeptides of PMP22 and P0 to detect domain-specific
      interactions between these proteins. The results revealed that PMP22 and P0 are
      involved in both trans-homophilic and trans-heterophilic interactions. Moreover,
      the data clearly indicate that the heterophilic trans-interaction is mediated
      through the second loop of PMP22, while the first loop is involved in homophilic
      trans-interaction of PMP22 proteins. Both modes of interaction are due to direct
      protein-protein binding. In addition, we demonstrate that disease-related point
      mutations of P0 resulted in a decreased adhesion capability correlating with the
      severity of the respective disease phenotype.

PMID- 15555917
TI  - Neuregulin-1beta induces neurite extension and arborization in cultured
      hippocampal neurons.
AB  - Neuregulin-1 (NRG-1) growth and differentiation factors and their erbB receptors
      are hypothesized to promote embryonic hippocampal neuron differentiation via as
      yet unknown mechanisms. We have found that NRG-1beta increases the outgrowth of
      primary neurites, neuronal area, total neurite length, and neuritic branching in
      E18 hippocampal neurons. NRG-1beta effects on neurite extension and arborization
      are similar to, but not additive with, those of brain-derived neurotrophic factor
      and reflect direct NRG-1 action on hippocampal neurons as these cells express the
      NRG-1 receptors erbB2 and erbB4, the erbB-specific inhibitor PD158780 decreases
      NRG-1beta induced neurite outgrowth, and NRG-1beta stimulation induces p42/44 ERK
      phosphorylation. Pharmacological inhibition of p42/44 ERK and protein kinase C
      (PKC), but not PI3K or p38 MAP kinase, inhibits NRG-1beta-induced neurite
      extension and elaboration. We conclude that NRG-1beta stimulates hippocampal
      neurite extension and arborization via a signaling pathway that involves erbB
      membrane tyrosine kinases (erbB2 and/or erbB4), p42/44 ERK, and PKC.

PMID- 15555919
TI  - Stimulated regeneration of the crushed adult rat optic nerve correlates with
      attenuated expression of the protein tyrosine phosphatases RPTPalpha, STEP, and
      LAR.
AB  - We have evaluated the spatial and temporal expression patterns of three protein
      tyrosine phosphatases (PTPs), receptor PTPalpha (RPTPalpha), striatal enriched
      phosphatase (STEP), and leucocyte common antigen-related phosphatase (LAR), in
      the retina and optic nerve (ON) of adult rats in which the crushed ON was either
      regenerating after retinal ganglion cell (RGC) stimulation with intravitreal
      peripheral nerve (PN) grafting or lens injury (LI), or not regenerating (no
      treatment). In intact adult rats, all three PTPs were expressed by RGCs and ON
      glia. In both the regenerating and non-regenerating models, a postlesion rise in
      RPTPalpha, STEP, and LAR expression occurred in the RGC somata and in the ON.
      However, for RPTPalpha and LAR in the RGCs, and for RPTPalpha, STEP, and LAR in
      the ON, this postlesion increase was attenuated in the regenerating versus the
      non-regenerating models. ON PTP expression changes were localized to glia in the
      proximal and distal stumps, and to macrophages and extracellular matrix of the
      glial scar at the lesion site. Interestingly, neither RPTPalpha, STEP, nor LAR
      localized to intact or regenerating axons. One explanation of these findings is
      that RPTPalpha and LAR may modulate RGC survival, and that RPTPalpha, STEP, and
      LAR may modulate axon growth.

PMID- 15555918
TI  - Morphologically identified glycinergic synapses in the hippocampus.
AB  - Inhibitory transmission in the hippocampus is predominantly GABAergic, but
      electrophysiological data evidenced strychnine-sensitive glycine-induced
      currents. However, synaptic currents have not been reported. Here, we describe,
      for the first time, the presence of GlyR clusters in several areas of the
      hippocampus as well as in cultured hippocampal neurons. In contrast with spinal
      cord, hippocampal GlyRs contain alpha2 but no alpha1 subunit. Optical and
      electron microscopy indicates that GlyRs can be synaptic as well as
      extrasynaptic. Synaptic GlyRs were apposed to glycinergic boutons characterized
      by the expression of the vesicular and the plasma membrane transporters of
      glycine (VIAAT and GlyT2, respectively). Double labeling with calcium-binding
      proteins showed that GlyT2 could be detected in boutons innervating both
      excitatory cells (soma and dendrites) and interneurons. Finally, GlyR clusters
      could be detected at synaptic sites with the GABAA receptor gamma2 subunit and
      gephyrin, suggesting that mixed GABA/glycine synapses might exist in the
      hippocampus.

PMID- 15555920
TI  - Inhibition of N-linked glycosylation prevents inclusion formation by the dystonia
      related mutant form of torsinA.
AB  - Most cases of early-onset torsion dystonia are associated with a mutation in the
      DYT1 gene that results in the loss of a glutamic acid residue in the carboxy
      terminus of the encoded protein, torsinA. When overexpressed in cultured cells,
      wild-type torsinA distributes diffusely throughout the endoplasmic reticulum
      (ER), while the dystonia-related mutant, torsinADeltaE, accumulates within
      multilamellar membrane inclusions. Here we show that inclusion formation requires
      the addition of an N-linked oligosaccharide to one of two asparagine residues
      within the ATP-binding domain of the mutant protein. In the absence of this
      modification, overexpressed torsinADeltaE was localized diffusely throughout the
      cell in a reticular pattern resembling that of wild-type torsinA. In contrast,
      the localization of wild-type torsinA did not appear to vary with its
      glycosylation state. These results thus indicate that torsinADeltaE must achieve
      a specific conformation to induce formation of intracellular membrane inclusions.

PMID- 15555921
TI  - Imaging the motility of dendritic protrusions and axon terminals: roles in axon
      sampling and synaptic competition.
AB  - Dendritic spines and filopodia display actin-based morphological plasticity. The
      function of this rapid motility is unknown. Its ubiquitous expression during
      development has led to the hypothesis that motility plays a role in
      synaptogenesis. We investigated this by simultaneously imaging presynaptic
      boutons and dendritic protrusions in acute hippocampal slices from GFP-M
      transgenic mice loaded with FM 1-43 followed by immunostaining. Postsynaptic
      motility was inversely correlated with the presence of stable synaptic contacts.
      Filopodia were highly motile and made transient interactions, whereas spines were
      less motile and had stable contacts, although they could still move together with
      a synaptic terminal. "Head morphing" of spines was associated with interactions
      with more than one presynaptic terminal. Our data indicate that filopodia
      motility could serve to transiently sample the surrounding neuropil, while the
      motility of established spines could mediate interactions with two axonal
      terminals. Spine "morphing" could therefore be the morphological signature for
      synaptic input competition in central synapses.

PMID- 15555922
TI  - HGF promotes survival and growth of maturing sympathetic neurons by PI-3 kinase-
      and MAP kinase-dependent mechanisms.
AB  - Hepatocyte growth factor (HGF) is a pleiotrophic factor whose many functions
      include promoting neuronal survival and growth. Hitherto, these effects have been
      observed in the presence of other neurotrophic factors like NGF and CNTF, and
      this requirement for an accessory factor has made it difficult to elucidate the
      signaling pathways that mediate its survival and growth-enhancing effects. Here,
      we show that HGF promotes the survival of mature sympathetic neurons of the
      superior cervical ganglion (SCG) grown at low density in defined medium lacking
      other neurotrophic factors. This effect was first clearly observed in cultures
      established from postnatal day 20 (P20) mice and became maximal by P40. HGF also
      enhanced the growth of neurite arbors from neurons throughout postnatal
      development and in the adult. HGF treatment resulted in phosphorylation of Akt
      and ERK1/ERK2. Preventing Akt activation with the phosphatidylinositol-3 (PI-3)
      kinase inhibitor LY294002 blocked the HGF survival response, and inhibition of
      ERK activation with the MEK inhibitors PD98059 or U0126 reduced the HGF survival
      response and the neurite growth-promoting effects of HGF. These results indicate
      that HGF promotes the survival and growth of maturing sympathetic neurons by both
      PI-3 kinase- and MAP kinase-dependent mechanisms.

PMID- 15555923
TI  - Nuclear expression of S100B in oligodendrocyte progenitor cells correlates with
      differentiation toward the oligodendroglial lineage and modulates
      oligodendrocytes maturation.
AB  - The S100B protein belongs to the S100 family of EF-hand calcium binding proteins
      implicated in cell growth and differentiation. Here, we show that in the
      developing and the adult mouse brain, S100B is expressed in oligodendroglial
      progenitor cells (OPC) committed to differentiate into the oligodendrocyte (OL)
      lineage. Nuclear S100B accumulation in OPC correlates with the transition from
      the fast dividing multipotent stage to the morphological differentiated, slow
      proliferating, pro-OL differentiation stage. In the adult, S100B expression is
      down-regulated in mature OLs that have established contacts with their axonal
      targets, suggesting a nuclear S100B function during oligodendroglial cells
      maturation. In vitro, the morphological transformation and maturation of pro-OL
      cells are delayed in the absence of S100B. Moreover, mice lacking S100B show an
      apparent delay in OPC maturation in response to demyelinating insult. We propose
      that nuclear S100B participates in the regulation of oligodendroglial cell
      maturation.

PMID- 15555924
TI  - Estrogen deficiency leads to apoptosis in dopaminergic neurons in the medial
      preoptic area and arcuate nucleus of male mice.
AB  - The aromatase knockout (ArKO) mouse is unable to synthesize estrogens.
      Immunohistochemical studies on active caspase-3 and tyrosine hydroxylase (TH)
      revealed apoptosis of dopaminergic neurons in the medial preoptic area (MPO) and
      arcuate nucleus (Arc) of the hypothalamus of 1-year-old (1yo) male ArKO mice
      while no active caspase-3 was detected in wild type (WT). Furthermore, the number
      of TH-positive cells in the MPO and caudal Arc was significantly decreased in 1yo
      ArKO compared to WT. RNase protection assays support the presence of apoptosis in
      1yo ArKO hypothalamus, revealing an up-regulation of pro-apoptotic genes: FASL,
      FADD, and caspase-8. Concomitantly, the ratio of bcl-2-related anti-apoptotic
      genes to pro-apoptotic genes in the hypothalamus of 1yo ArKO mice was
      significantly down-regulated. Previously, we have reported that no such changes
      were observed in the hypothalamus of female ArKO mice. Thus, we have provided
      direct evidence that estrogen is required to maintain the survival and functional
      integrity of dopaminergic neurons in the MPO and Arc of male, but not female
      mice.

PMID- 15555925
TI  - The extracellular matrix component WIF-1 is expressed during, and can modulate,
      retinal development.
AB  - We have shown previously that components of the extracellular matrix (ECM)
      modulate neuronal development. Here, we searched for additional ECM elements that
      might play roles in retinal histogenesis and identified a secreted glycoprotein
      that is heavily expressed in the retina. This molecule, named by others Wnt
      Inhibitory Factor-1 (WIF-1), is expressed during and after the period of rod
      photoreceptor morphogenesis in the mouse. We show that a potential WIF-1 ligand,
      Wnt4, as well as a potential Wnt4 receptor, fzd4, and a potential Wnt4
      coreceptor, LRP6, are expressed in the region of, and at the time of, rod
      photoreceptor genesis. WIF-1 and Wnt4 are coexpressed during retinal development
      and bind to each other; therefore, they are likely to interact during rod
      production. WIF-1 protein inhibits rod production, and anti-WIF-1 antibodies
      increase rod production; in contrast, Wnt4 promotes rod production. Together,
      these data suggest that WIF-1 and Wnt4, both components of the ECM, regulate
      mammalian photoreceptor development.

PMID- 15555926
TI  - Inducible production of interferon-gamma in the developing brain causes
      cerebellar dysplasia with activation of the Sonic hedgehog pathway.
AB  - Here we examined the role of interferon (IFN)-gamma in regulating the Sonic
      hedgehog (Shh) pathway and cerebellar development in bigenic mice with temporal
      control of IFN-gamma gene expression driven by a tetracycline-controllable
      promoter. In IFN-gamma-expressing but not age-matched non-IFN-gamma-expressing
      bigenic or control mice, development of the cerebellum was severely affected with
      the persistence and extensive proliferation of the external granule neuron layer
      (EGL) and infiltration with modest numbers of T-lymphocytes. Following induction
      of IFN-gamma transgene expression, both total and tyrosine-phosphorylated signal
      transducer and activator of transcription (STAT)1 (the major transcriptional
      factor for IFN-gamma), phosphorylated STAT3 and STAT5, and expression of a number
      of IFN-gamma-regulated genes were significantly increased in cerebellum. In the
      cerebellum from IFN-gamma-expressing but not age-matched non-IFN-gamma-expressing
      mice, the level of Shh and Gli-1 but not Patched (Ptch) 1 RNA was increased as
      was the 19-kDa signaling product of the Shh precursor protein. In situ
      localization studies revealed ectopic expression of the Shh gene by the granule
      neurons. We conclude that IFN-gamma directly affects the proliferation and fate
      of EGL neurons in the cerebellum by activating the Shh pathway and stimulating an
      autocrine growth response by these cells.

PMID- 15555927
TI  - Synaptic scaffolding molecule is involved in the synaptic clustering of
      neuroligin.
AB  - S-SCAM has a similar molecular organization to PSD-95. Both of them interact with
      a cell adhesion molecule, neuroligin. We previously reported that beta-catenin
      binds S-SCAM and recruits it to synapses. We have here examined using rat primary
      cultured neurons whether neuroligin recruits S-SCAM to synapses or S-SCAM
      determines the localization of neuroligin. Overexpressed neuroligin formed larger
      clusters under co-expression of S-SCAM but not of PSD-95. Overexpressed
      neuroligin blocked synaptic accumulation of PSD-95 but not of S-SCAM. S-SCAM
      mutant containing the neuroligin-binding region interfered with synaptic
      accumulation of neuroligin and PSD-95, whereas the similar mutant of PSD-95 had
      no effect. Biochemical studies revealed that neuroligin forms a ternary complex
      with S-SCAM and PSD-95 through manifold interactions. These findings imply that S
      SCAM is tethered by beta-catenin to synapses and induces synaptic accumulation of
      neuroligin, which subsequently recruits PSD-95 to synapses.

PMID- 15555929
TI  - Pathological missense mutations of neural cell adhesion molecule L1 affect
      neurite outgrowth and branching on an L1 substrate.
AB  - A number of pathological missense mutations of L1CAM have been shown to disrupt
      L1-L1 homophilic binding and/or affect surface expression. To investigate whether
      these mutations disrupt L1-mediated neurite outgrowth, cerebellar neurons from L1
      knockout mice are transfected with WT human L1 or L1 mutant constructs, and grown
      on an L1 substrate. Various parameters of neurite growth are quantified. Most L1
      mutations do not affect neurite length significantly but several mutations cause
      a significant decrease in branching. Comparison of these data with data on L1
      expression levels and homophilic binding strength show that changes in neurite
      growth cannot be simply explained by reductions in either of these parameters.
      Our results suggest that a coreceptor is involved in L1-mediated neurite
      outgrowth. Some pathological mutations have little effect on L1 mediated neurite
      growth, so it is unlikely that a failure of L1-mediated neurite outgrowth is the
      principle cause of brain defects in patients with L1 mutations.

PMID- 15555928
TI  - Temporally distinct demands for classic cadherins in synapse formation and
      maturation.
AB  - Classic cadherins are synaptic adhesion proteins that have been implicated in
      synapse formation and targeting. Brief inactivation of classic cadherin function
      in young neurons appears to abrogate synapse formation when examined acutely. It
      remains unknown if such abrogation is unique to young neurons, whether it occurs
      by stalling neuronal maturation or by directly interfering with the process of
      synapse assembly, or whether synapse targeting is altered. Here we asked if
      sustained pan-cadherin blockade would prevent or alter the progression of axonal
      and dendritic outgrowth, synaptogenesis, or the stereotypic distribution of
      excitatory and inhibitory synapses on cultured hippocampal neurons. While pre-
      and postsynaptic cadherins are required for synapse assembly in young neurons, we
      find that in neurons older than 10 days, classic cadherins are entirely
      dispensable for joining and aligning presynaptic vesicle clusters with molecular
      markers of the postsynaptic density. Furthermore, we find that the proportion and
      relative distributions of excitatory and inhibitory terminals on single neurons
      are not altered. However, synapses that form on neurons in which cadherin
      function is blocked are smaller; they exhibit decreased synaptic vesicle
      recycling and a decreased frequency of spontaneous EPSCs. Moreover, they fail to
      acquire resistance to F-actin depolymerization, a hallmark of mature, stable
      contacts. These data provide new evidence that cadherins are required to promote
      synapse stabilization and structural and functional maturation, but dispensable
      for the correct subcellular distribution of excitatory and inhibitory synapses.

PMID- 15555930
TI  - BMP4 and CNTF are neuroprotective and suppress damage-induced proliferation of
      Muller glia in the retina.
AB  - In response to acute damage, Muller glia in the chicken retina have been shown to
      be a source of proliferating progenitor-like cells. The secreted factors and
      signaling pathways that regulate this process remain unknown. The purpose of this
      study was to test whether secreted factors, which are known to promote glial
      differentiation during development, regulate the ability of Muller glia to
      proliferate and become retinal progenitors in response to acute damage in mature
      retina. We made intraocular injections of BMP4, BMP7, EGF, NGF, BDNF, or CNTF
      before or after a single, toxic dose of N-methyl-d-aspartate (NMDA) and assayed
      for proliferating progenitor-like cells within the retina. We found that
      injections of BMP4, BMP7, or CNTF, but not EGF, NGF, or BDNF, before NMDA
      treatment reduced the number of Muller glia that proliferated and gave rise to
      progenitor-like cells. CNTF and BMP4, but not NGF or BDNF, greatly reduced the
      number of cells destroyed by toxin treatment indicating that these factors
      protect retinal neurons from a severe excitotoxic insult. Injections of CNTF 5
      days before NMDA treatment prevented neurotoxin-induced cell death and Muller
      glial proliferation, while injections of BMP4 had no protective effect. In
      addition, CNTF injected after NMDA treatment suppressed glial proliferation,
      while BMP4 did not. We conclude that BMP4 and CNTF, when applied before a toxic
      insult, act as neuroprotective agents and likely suppress the proliferative
      response of Muller glia to retinal damage by attenuating the retinal damage;
      protecting bipolar and amacrine neurons from NMDA-induced cell death. When
      applied after a toxic insult, CNTF suppressed glial proliferation independent of
      levels of retinal damage.

PMID- 15555931
TI  - The in vivo and in vitro characterization of DnaK from Agrobacterium tumefaciens
      RUOR.
AB  - Molecular chaperones of the heat shock protein 70 family (Hsp70; also called DnaK
      in prokaryotes) play an important role in the folding and functioning of cellular
      protein machinery. The dnaK gene from the plant pathogen Agrobacterium
      tumefaciens RUOR was amplified using the polymerase chain reaction and the DnaK
      protein (Agt DnaK) was over-produced as a His-tagged protein in Escherichia coli.
      The Agt DnaK amino acid sequence was 96% identical to the A. tumefaciens C58 DnaK
      sequence and 65% identical to the E. coli DnaK sequence. Agt DnaK was shown to be
      able to functionally replace E. coli DnaK in vivo using complementation assays
      with an E. coli dnaK756 mutant strain and a dnaK52 deletion strain. Over
      production and purification of Agt DnaK was successful, and allowed for further
      characterization of the protein. Kinetic analysis of the basal ATPase activity of
      purified Agt DnaK revealed a Vmax of 1.3 nmol phosphate released per minute per
      milligram DnaK, and a Km of 62 microM ATP. Thus, this is the first study to
      provide both in vivo and in vitro evidence that Agt DnaK has the properties of a
      molecular chaperone of the Hsp70 family.

PMID- 15555932
TI  - A method for the purification of Shiga-like toxin 1 subunit B using a
      commercially available galabiose-agarose resin.
AB  - We describe a procedure for the affinity purification of Shiga toxin 1 subunit B
      (SLTB) using a commercial galabiose-agarose resin. Recombinant SLTB was purified
      to 99% homogeneity in a single-step protocol, from the periplasmic extracts of
      Vibrio cholerae 0395 N1/pSBC54. SDS-PAGE of the affinity purified SLTB showed one
      band of 8 kDa MW. SLTB purified by this procedure retained its chemical and
      biological activity as demonstrated by re-binding to the galabiose-agarose resin,
      and receptor-mediated binding and uptake in Vero cells. The galabiose-agarose
      resin could isolate roughly 1mg of SLTB/mL of gel. The resin was stable over 3
      years and 500 cycles/year of usage. Hence, this method is a straightforward
      approach to the large-scale preparation of SLTB at a reasonable cost.

PMID- 15555933
TI  - Purification and characterization of a recombinant version of human alpha
      fetoprotein expressed in the milk of transgenic goats.
AB  - Alpha-Fetoprotein (AFP) is a 68 kDa glycoprotein expressed at high levels by the
      fetal liver and yolk with transcription repressed to very low levels after birth.
      Transfer of fetal AFP through the placenta into the circulation of the mother is
      correlated with remission of rheumatoid arthritis, multiple sclerosis, and other
      autoimmune disorders. AFP is therefore under development as a biopharmaceutical
      for the treatment of autoimmune diseases. The clinical evaluation of AFP requires
      the production of hundreds of grams of highly purified and biologically active
      protein. We have produced goats that express a form of the human AFP transgene
      under the control of the beta-casein promoter. In this form of rhAFP, the single
      N-linked glycosylation site was removed by mutagenesis (N233Q). Here, we describe
      a purification protocol for this recombinant human (rh)AFP from the milk of these
      transgenic goats. A three-column procedure was developed to produce gram
      quantities of highly purified rhAFP. Near- and far-UV circular dichroism spectra
      of human umbilical cord blood AFP and rhAFP were essentially identical,
      suggesting that the structure is not affected by removal of the glycosylation
      site. Furthermore, the cell binding and pharmacokinetics of purified rhAFP were
      similar to human AFP isolated from cord blood. Our results demonstrate that an
      active form of rhAFP can be produced on industrial scale by expression in
      transgenic goat milk.

PMID- 15555934
TI  - High-level production of recombinant sulfide-reactive hemoglobin I from Lucina
      pectinata in Escherichia coli. High yields of fully functional holoprotein
      synthesis in the BLi5 E. coli strain.
AB  - Hemoglobin I (HbI) from Lucina pectinata is a monomeric protein composed of 143
      amino acids with high sulfide affinity. Its unique heme pocket contains three
      residues not commonly found in vertebrate globins: Phe 29 (B10), Gln 64 (E7), and
      Phe 68 (E11), which are thought to be important for high affinity for hydrogen
      sulfide. Recombinant HbI (rHbI) and several site-directed mutants were cloned and
      expressed in Escherichia coli yielding high amounts of protein. The highest rHbI
      protein yield was obtained when the HbI cDNA was cloned into the pET28 (a+)
      expression vector, transformed into BLi5 cells, the induction performed with 1 mM
      IPTG at 30 degrees C and TB medium was supplemented with 30 microg/mL hemin
      chloride and 1% glucose. The highest yield obtained of HbI was 32 mg/L of culture
      using Fernbach flasks. UV/Visible spectral analysis showed that rHbI binds heme
      and ESI-MS shows that its molecular weight corresponds to the expected size.
      Kinetic studies with H2S confirmed that rHbI and HbI have identical binding
      properties, where the kON for the clam's Hb is 2.73x10(4)M-1s-1 and for rHbI is
      2.43x10(4)M-1s-1.

PMID- 15555935
TI  - Expression of chitin deacetylase from Colletotrichum lindemuthianum in Pichia
      pastoris: purification and characterization.
AB  - The chitin deacetylase gene from Colletotrichum lindemuthianum UPS9 was isolated
      and cloned in Pichia pastoris as a tagged protein with six added terminal
      histidine residues. The expressed enzyme was recovered from the culture
      supernatant and further characterized. A single-step purification based on
      specific binding of the histidine residues was achieved. The purified enzyme has
      a molecular mass of 25 kDa and is not glycosylated as determined by mass
      spectrometry. The activity of the recombinant chitin deacetylase on chitinous
      substrates was investigated. With chitotetraose as substrate, the optimum
      temperature and pH for enzyme activity are 60 degrees C and 8.0, respectively.
      The specific activity of the pure protein is 72 U/mg. One unit of enzyme activity
      is defined as the amount of enzyme that produces 1 micromol of acetate per minute
      under the assay conditions employed. The enzyme activity is enhanced in the
      presence of Co2+ ions. A possible use of the recombinant chitin deacetylase for
      large-scale biocatalytic conversion of chitin to chitosan is discussed.

PMID- 15555937
TI  - Identification and removal of O-linked and non-covalently linked sugars from
      recombinant protein produced using Pichia pastoris.
AB  - The use of the methylotrophic yeast Pichia pastoris for large-scale recombinant
      production of proteins for therapeutic uses and/or biophysical characterisation
      has been gaining popularity. Here we describe the use of this organism for the
      production of a von Willebrand factor C domain from procollagen IIA for solution
      NMR studies. In this research, we specifically identified sites of O-linked
      glycosylation on the expressed protein, although the native protein is not
      glycosylated. We demonstrated that it was possible to remove the oligosaccharides
      by enzymatic digestion, however this approach proved to be prohibitively
      expensive for the scale of production required for high-resolution structural
      studies by NMR spectroscopy. After removal of the O-linked glycosylation sites by
      site-directed mutagenesis, we confirmed that the protein was no longer covalently
      glycosylated. However, analysis by 1H- and 13C-edited spectroscopy identified the
      presence of non-covalently associated glycans which were removed by lectin
      affinity chromatography. We have synthesised methods for the identification and
      removal of both covalently and non-covalently bound oligosaccharides from
      heterologous protein expressed in P. pastoris.

PMID- 15555936
TI  - Intranasal administration of an Escherichia coli-expressed codon-optimized
      rotavirus VP6 protein induces protection in mice.
AB  - We are developing rotavirus vaccines based on the VP6 protein of the human G1P[8]
      [corrected] [J. Virol. 73 (1999) 7574] CJN strain of rotavirus. One prototype
      candidate consisting of MBP::VP6::His6, a chimeric protein of maltose-binding
      protein, VP6 and hexahistidine, was expressed mainly as truncated polypeptides in
      Escherichia coli BL21(DE3) cells. A possible reason for this extensive truncation
      is the high frequencies of rare bacterial codons within the rotavirus VP6 gene.
      Expression of truncated recombinant VP6 was found to be reduced, and expression
      of complete VP6 protein was simultaneously increased, when the protein was
      expressed in Rosetta(DE3)pLacI E. coli cells that contain increased amounts of
      transfer RNAs for a selection of rare codons. The same observation was made when
      a synthetic codon-optimized CJN-VP6 gene was expressed in E. coli BL21 or Rosetta
      cells. To increase protein recovery, recombinant E. coli cells were treated with
      8M urea. Denatured, full-length MBP::VP6::His6 protein was then purified and used
      for intranasal vaccination of BALB/c mice (2 doses administered with E. coli heat
      labile toxin LT(R192G) as adjuvant). Following oral challenge with the G3P[16]
      [corrected] [J. Virol. 76 (2002) 560] EDIM strain of murine rotavirus, protection
      levels against fecal rotavirus shedding were comparable (P>0.05) between groups
      of mice immunized with denatured codon-optimized or native (not codon-optimized)
      immunogen with values ranging from 87 to 99%. These protection levels were also
      comparable to those found after immunization with non-denatured CJN VP6. Thus,
      expression of complete rotavirus VP6 protein was greatly enhanced by codon
      optimization, and the protection elicited was not affected by denaturation of
      recombinant VP6.

PMID- 15555938
TI  - Overexpression in Escherichia coli and purification of pteridine reductase (PTR1)
      from a clinical isolate of Leishmania donovani.
AB  - Pteridine reductase 1 (PTR1) is part of a novel metabolic pathway in Leishmania
      associated with folate metabolism. Its main function is to salvage pterins but a
      second one is to reduce folates. The novelty and possible uniqueness of the
      pathway in which PTR1 is involved opens the possibility of developing specific
      inhibitors, which in combination with dihydrofolate reductase inhibitors could be
      highly effective against Leishmania. In order to increase our understanding of
      this putative important chemotherapeutic target, we present here the cloning,
      overexpression and purification of this enzyme from a clinical isolate of
      Leishmania donovani causing kala azar in India. This recombinant enzyme will set
      the basis for inhibition studies as well as for structure-function relationships.

PMID- 15555939
TI  - Intracellular domains of the delta-subunits of Torpedo and rat acetylcholine
      receptors--expression, purification, and characterization.
AB  - There are quite detailed structural data on the extracellular ligand-binding
      domain and the intramembrane channel-forming domain of the nicotinic
      acetylcholine receptors (nAChR). However, the structure of the intracellular
      domain, which has variable amino acid sequences in different nAChR subunits,
      remains unknown. We expressed in Escherichia coli the intracellular loops
      (between transmembrane fragments TM3 and TM4) of the delta-subunits from the
      Torpedo californica and Rattus norvegicus muscle nAChRs. To facilitate
      purification, (His)6-tags were attached with or without linkers, and the effects
      of protein truncations at C- or N-termini were examined. The proteins were
      purified from inclusion bodies under denaturing conditions by Ni-NTA
      chromatography. Molecular weight and peptide mass fingerprint was determined by
      MALDI mass spectrometry. Size-exclusion chromatography revealed that the Torpedo
      intracellular delta-loop refolded in an aqueous buffer was present in solution as
      a dimer. Phosphorylation of this protein with protein kinase A and tyrosine
      kinase (Abl) occurred at the same serine and tyrosine residues as in the native
      receptor. According to CD spectra, the secondary structure was not sensitive to
      phosphorylation. The rat intracellular loops could be solubilized only in the
      presence of non-ionic detergents or lipids. CD spectra indicate that the Torpedo
      and rat proteins have differences in their secondary structure. In the presence
      of dodecylphosphocholine, high concentrations (up to 6 mg/ml) of the Torpedo and
      rat intracellular loops were achieved. The results suggest that the spatial
      structure of the intracellular loops is dependent on environment and species, but
      is not changed significantly upon enzymatic phosphorylation.

PMID- 15555940
TI  - Expression in Trichoderma reesei and characterisation of a thermostable family 3
      beta-glucosidase from the moderately thermophilic fungus Talaromyces emersonii.
AB  - The gene encoding a thermostable beta-glucosidase (cel3a) was isolated from the
      thermophilic fungus Talalaromyces emersonii by degenerate PCR and expressed in
      the filamentous fungus Trichoderma reesei. The cel3a gene encodes an 857 amino
      acid long protein with a calculated molecular weight of 90.59 kDa. Tal. emersonii
      beta-glucosidase falls into glycosyl hydrolase family 3, showing approximately 56
      and 67% identity with Cel3b (GenBank ) from T. reesei, and a beta-glucosidase
      from Aspergillus Niger (GenBank ), respectively. The heterologously expressed
      enzyme, Cel3a, was a dimer equal to 130 kDa subunits with 17 potential N
      glycosylation sites and a previously unreported beta-glucosidase activity
      produced extracellularly by Tal. emersonii. Cel3a was thermostable with an
      optimum temperature of 71.5 degrees C and half life of 62 min at 65 degrees C and
      was a specific beta-glucosidase with no beta-galactosidase side activity. Cel3a
      had a high specific activity against p-nitrophenyl-beta-D-glucopyranoside (Vmax,
      512 IU/mg) and was competitively inhibited by glucose (k(i), 0.254 mM). Cel3a was
      also active against natural cellooligosacharides with glucose being the product
      of hydrolysis. It displayed transferase activity producing mainly cellobiose from
      glucose and cellotetrose from cellobiose.

PMID- 15555941
TI  - Expression, purification and structural characterization of the scaffoldin
      hydrophilic X-module from the cellulosome of Clostridium thermocellum.
AB  - The cellulosome is a membrane-bound, extracellular multi-subunit complex
      responsible for the degradation of crystalline cellulose by a number of organisms
      including anaerobic bacteria and fungi. The hydrophilic X-module (CipA-X) from
      the modular scaffoldin subunit of Clostridium thermocellum cellulosome has been
      proposed to play various roles in cellulosomal function, including thermal and
      structural stability. Towards elucidating the function of CipA-X using structural
      and biophysical studies, the region comprising residues 1692-1785 from the C.
      thermocellum CipA cDNA encoding CipA-X was cloned into a pET21b expression
      vector. When expressed in Escherichia coli, the C-terminal His-tagged protein
      accumulated in the insoluble fraction. Cell fractionation experiments showed that
      the recombinant protein was localized to inclusion bodies. Refolding and
      purification involved denaturation of the whole cell lysate by addition of urea,
      followed by a nickel-Sepharose chromatography step and dialysis into native
      conditions (25 mM Tris-HCl, pH 7.4, 50 mM NaCl, and 10 mM EDTA). A final gel
      filtration step purified the protein to homogeneity, yielding 40 mg/L. The two
      dimensional 1H-15N correlation spectrum of uniformly 15N-labelled CipA-X showed
      the characteristics of a well-folded protein comprising significant beta
      structure, which is in agreement with the circular dichroism data.

PMID- 15555942
TI  - High level recombinant protein expression in Ralstonia eutropha using T7 RNA
      polymerase based amplification.
AB  - We report further development of a novel recombinant protein expression system
      based on the Gram-negative bacterium, Ralstonia eutropha. In this study, we were
      able to express soluble, active, organophosphohydrolase (OPH), a protein that is
      prone to inclusion body formation in Escherichia coli, at titers greater than 10
      g/L in high cell density fermentation. This represents a titer that is
      approximately 100-fold greater than titers previously reported in E. coli for
      this enzyme. R. eutropha strains expressing OPH were generated in two cloning
      steps. First, the T7 RNA polymerase gene was placed under the control of the
      strong, inducible phaP promoter and integrated into the phaP locus of R. eutropha
      NCIMB 40124. Second, a single copy of the oph gene under control of the T7
      promoter was randomly integrated into the chromosome using a transposon cloning
      vector.

PMID- 15555943
TI  - Molecular cloning, overexpression, and purification of Micrococcus luteus K-3
      type glutaminase from Aspergillus oryzae RIB40.
AB  - We have for the first time found and cloned the cDNA (AoglsA) of Aspergillus
      oryzae RIB40, which encodes a 49.9-kDa protein sharing 40% homology with the salt
      tolerant glutaminase of Micrococcus luteus K-3 (Micrococcus glutaminase). AoglsA
      was subcloned into a series of expression vectors and expressed in Saccharomyces
      cerevisiae and Escherichia coli. The gene product, which we named AoGls, showed
      glutaminase activity and was produced in a cell wall fraction of S. cerevisiae
      and a soluble protein in E. coli. The highest expression level of 186 U/mg was
      obtained when the AoglsA was inserted into six bases downstream of the Shine
      Dalgarno (SD) sequence of pKK223-3 and expressed in E. coli Rosetta (DE3). AoGls
      was purified by SuperQ-TOYOPEARL, glutamine affinity chromatography, and Butyl
      TOYOPEARL. This is the first report on the overexpression and purification of a
      M. luteus K-3-type glutaminase cloned from an eucaryote.

PMID- 15555944
TI  - Production of human prolyl 4-hydroxylase in Escherichia coli.
AB  - Prolyl 4-hydroxylase (P4H) catalyzes the post-translational hydroxylation of
      proline residues in collagen strands. The enzyme is an alpha2beta2 tetramer in
      which the alpha subunits contain the catalytic active sites and the beta subunits
      (protein disulfide isomerase) maintain the alpha subunits in a soluble and active
      conformation. Heterologous production of the native alpha2beta2 tetramer is
      challenging and had not been reported previously in a prokaryotic system. Here,
      we describe the production of active human P4H tetramer in Escherichia coli from
      a single bicistronic vector. P4H production requires the relatively oxidizing
      cytosol of Origami B(DE3) cells. Induction of the wild-type alpha(I) cDNA in
      these cells leads to the production of a truncated alpha subunit (residues 235
      534), which assembles with the beta subunit. This truncated P4H is an active
      enzyme, but has a high Km value for long substrates. Replacing the Met235 codon
      with one for leucine removes an alternative start codon and enables production of
      full-length alpha subunit and assembly of the native alpha2beta2 tetramer in E.
      coli cells to yield 2 mg of purified P4H per liter of culture (0.2 mg/g of cell
      paste). We also report a direct, automated assay of proline hydroxylation using
      high-performance liquid chromatography. We anticipate that these advances will
      facilitate structure-function analyses of P4H.

PMID- 15555945
TI  - Protease domain of human ADAM33 produced by Drosophila S2 cells.
AB  - Human ADAM33 is a multiple-domain, type-I transmembrane zinc metalloprotease
      recently implicated in asthma susceptibility [Nature 418 (2002) 426]. To provide
      an active protease for functional studies, expression of a recombinant ADAM33
      zymogen (pro-catalytic domains, pro-CAT) was attempted in several insect cells.
      The pro-CAT was cloned into baculovirus under the regulation of the polyhedron
      promoter and using either the honeybee mellitin or ADAM33 signal sequence. Sf9 or
      Hi5 cells infected with these recombinant viruses expressed the majority of the
      protein unprocessed and as inclusion bodies ( approximately 10 mg/L). On the
      other hand, similar constructs could be expressed, processed, and secreted by
      Drosophila S2 cells using a variety of constitutive (actin, pAc5.1) or inducible
      (metallothionein, PMT) promoters and leader sequences (e.g., native and BiP).
      Higher expression level of 10-fold was observed for the inducible system
      resulting in an average yield of 20 mg/L after purification. The majority of the
      catalytic domain purified from the Drosophila conditioned media remained
      associated with the pro-domain after several chromatography steps. An induction
      cocktail containing cadmium chloride and zinc chloride was subsequently developed
      for the PMT system as an alternative to using cupric sulfate or cadmium chloride
      as single inducers. The novel induction cocktail resulted in an increased ratio
      of secreted catalytic to pro-domain, and yielded milligram amounts of highly
      purified protease. The availability of this modified expression system
      facilitated purification of the wild type and several glycosylation mutants, one
      of which (N231Q) crystallized recently for X-ray structure determination [J. Mol.
      Biol. 335 (2003) 129].

PMID- 15555948
TI  - Principles of endosonography and imaging.
AB  - Accurate interpretation of ultrasound images requires knowledge of the principles
      of ultrasound and how it interacts with tissue. This article outlines the
      important principles that every endosonographer should know and provides clinical
      implications to make the material relevant to endosonographers.

PMID- 15555949
TI  - Endoscopic ultrasonography: equipment and technique.
AB  - By definition, endoscopic ultrasonography (EUS) combines endoscopy and high
      frequency ultrasound, incorporating a small ultrasonic transducer into the tip of
      endoscopes. For the upper gastrointestinal tract, mostly oblique-viewing
      endoscopes are used, although recently, forward viewing instruments have become
      available. For colorectal EUS, rigid probes for the rectum and a flexible forward
      viewing echocolonoscope are available. EUS generates ultrasound either
      mechanically or electronically, depending on the type of instrument used. The
      electronic technique potentially allows the incorporation of (color) Doppler
      ultrasound, which allows for additional processing and postprocessing functions.
      This generally is considered the EUS technique of the future.

PMID- 15555950
TI  - Submucosal lesions.
AB  - Most of the submucosal lesions encountered on endoscopy are benign; however, the
      fact that some of them may be malignant considerably influences the attitude
      toward the whole group. This article reviews the current status of endosonography
      in the management of submucosal lesions and focuses on determining the risk of
      malignancy. The predictive value of various endoscopic ultrasonography (EUS)
      features and their combinations and the capabilities and limitations of EUS
      guided fine needle biopsy are discussed. Other issues addressed include
      differentiation between extraluminal compressions and true submucosal lesions,
      EUS-assisted endoscopic removal of submucosal lesions, and the potential role of
      catheter-based endosonography in the setting of submucosal lesions. Problems
      related to the surveillance of patients with submucosal lesions who are not
      candidates for surgical treatment are outlined. An overview of the recent changes
      in the pathologic classification of gastrointestinal mesenchymal tumors and their
      impact on the role of EUS in the management of submucosal lesions is given.

PMID- 15555951
TI  - Chronic pancreatitis.
AB  - In the past 20 years, endoscopic ultrasonography has been added to the already
      large armamentarium of diagnostic tests for chronic pancreatitis. This article
      discusses its potential and possible limitations.

PMID- 15555952
TI  - Biliary stones: including acute biliary pancreatitis.
AB  - The widespread availability of endoscopic ultrasound has facilitated the
      evaluation of the pancreas and extrahepatic biliary system. Endosonography has
      been shown to be highly sensitive in the detection of choledocholithiasis
      (especially in patients with small stones and nondilated bile ducts) and
      gallbladder microlithiasis; however, the use of this technique in relation to
      endoscopic retrograde cholangiography and laparoscopic surgery in gallstone
      disease remains confusing. This article highlights the clinical performance and
      results of endoscopic ultrasound in this context and proposes strategies in
      relation to its use in association with endoscopic retrograde
      cholangiopancreatography and surgery in common clinical practice. Endosonography
      allows the correct identification of patients with acute biliary pancreatitis and
      proves an important adjunct in eliminating other causes of undetermined
      pancreatitis.

PMID- 15555953
TI  - Barrett's esophagus.
AB  - Esophageal cancer staging is a widely accepted indication for endoscopic
      ultrasonography (EUS). The evaluation of Barrett's esophagus (BE) with EUS is
      indicated only when there is high-grade dysplasia or a concern for malignancy in
      an endoscopic lesion. Because the options for the management of BE and early
      adenocarcinoma are diverse, proper selection of patients by accurate staging with
      EUS is critical, particularly when nonoperative management is considered. For
      example, patients with BE with high-grade dysplasia may be offered esophagectomy
      in some medical centers, but nonoperative therapies such as endoscopic ablative
      therapy or mucosal resection may be the preferred treatment options in other
      gastroenterology practices. This article discusses the scientific evidence for
      the use of EUS in BE or early esophageal adenocarcinoma.

PMID- 15555954
TI  - Role of endoscopic ultrasonography in the diagnosis of early esophageal
      carcinoma.
AB  - Endoscopic ultrasonography (EUS) for the diagnosis and staging of early
      esophageal carcinoma is discussed. Based on the nine-layered structure of
      esophageal wall, which is in good correspondence with histological layers, depth
      of carcinoma invasion can be investigated. Ultrasound endoscopes and probes are
      used for the examination. Ultrasound probes with 20 MHz and 30 MHz transducers
      can demonstrate the clear images of early esophageal carcinoma by using water
      filling method, which can discuss the change of the esophageal wall from the
      surface layer. Although the early esophageal carcinoma is detected by endoscopic
      findings with or without the dye spraying method by iodine, the diagnosis of
      depth of carcinoma invasion is not easy. EUS can assist in the diagnosis of depth
      of carcinoma invasion. Confirming the depth of carcinoma invasion by EUS and the
      lesion is limited to the mucosa. Endoscopists can decide the indication for
      endoscopic resection of the lesions.

PMID- 15555955
TI  - Advanced esophageal cancer.
AB  - Although the prognosis for patients with early cancer is good, throughout the
      world the majority of patients present with advanced disease, and in them,
      survival is poor. Accurate staging is essential to inform prognosis; to select
      candidates who may be cured by surgery alone; to select patients requiring
      neoadjuvant therapy, especially when new protocols are being studied; and to
      detect patients with advanced disease who would be best served by palliative
      therapy.

PMID- 15555956
TI  - Pancreatic neoplasms.
AB  - Patients who present with signs and symptoms suggesting a pancreatic neoplasm
      typically undergo initial imaging with transabdominal ultrasound or CT. When a
      pancreatic mass or fullness is identified, it may represent an inflammatory mass,
      benign process, or malignancy. Endoscopic ultrasound (EUS) is performed commonly
      to further characterize the lesion, obtain a tissue diagnosis, and for staging.
      This article reviews the role of EUS for the diagnosis and staging of pancreatic
      tumors.

PMID- 15555957
TI  - Cholangiocarcinoma and intraductal sonography.
AB  - The instruments and processing systems of intraductal ultrasonography (IDUS) and
      3D-IDUS are developing. IDUS is a reliable method for the evaluation of
      cholangiocarcinoma, and accurate staging is the most significant role of IDUS.
      DPR images produced by 3D-IDUS are useful to assess the tumor extension and the
      relationship with surrounding organs. 3D-IDUS is more useful for the precise
      diagnosis of cancer extension in cholangiocarcinoma, especially in invasion into
      the portal vein and pancreas, than CT scan and angiography. Tumor volume
      calculated with 3D-IDUS should determine the prognosis for the patients and
      facilitate the evaluation of efficacy of laser therapy.

PMID- 15555958
TI  - Endoscopic ultrasound and staging of non-small cell lung cancer.
AB  - This article outlines the basic principals of lung cancer staging and EUS-FNA
      techniques and suggests appropriate and inappropriate indications of EUS-FNA for
      lung cancer.

PMID- 15555959
TI  - Endoscopic ultrasound-guided fine-needle injection.
AB  - With the development of linear array echoendoscopes and the ability to perform
      endoscopic ultrasound (EUS)-guided fine-needle aspiration, the delivery of
      therapeutic agents with fine-needle injection (FNI) emerged. EUS-guided FNI is an
      attractive delivery system because of its minimal invasiveness and low
      complication rate. This approach is effective in performing celiac plexus
      neurolysis for pain relief in patients with pancreatic cancer. The most exciting
      area of interest involves the delivery of antitumor agents in patients with
      locally advanced cancer, such as cancer of the pancreas or esophagus. The
      involvement of EUS-guided FNI in tumor therapy adds a host of potential new
      applications that continue to swing the pendulum of EUS from a diagnostic to a
      therapeutic modality.

PMID- 15555960
TI  - Endoscopic ultrasound-guided pancreatic pseudocyst drainage.
AB  - In this article, we detail the different techniques of endoscopic ultrasound
      guided cystogastrostomy or duodenostomy and the complications and results of this
      new technical approach.

PMID- 15555961
TI  - Future therapeutic indications for endoscopic ultrasound.
AB  - Attempts to perform therapy guided by endoscopic ultrasound (EUS) are rare. Some
      new indications for interventional and therapeutic endoscopic procedures
      performed under EUS control have been developed in areas that have been purely
      surgical for many years. Indications, procedures, and related tools for EUS
      guided endosurgery are described, all of which are experimental but may open a
      new corridor for endoscopists to enter a variety of transluminal procedures in
      real time without soiling the peritoneal or mediastinal cavity.

PMID- 15555962
TI  - Noninvasive competition for endoscopic ultrasound.
AB  - Endoscopic ultrasonography (EUS) is one of the most significant developments in
      gastrointestinal (GI) imaging in recent years. EUS now plays a key role in the
      pretreatment staging of GI tract tumors and in the investigation of benign
      pancreaticobiliary pathology. It has not replaced conventional cross-sectional
      imaging (eg, ultrasound, CT, and MRI), but it has distinct properties and
      capabilities. EUS is most beneficial when used in a complementary fashion with
      cross-sectional and radionuclide imaging in the management of patients with GI
      tract disease. This article reviews the role of noninvasive imaging modalities in
      several clinical situations where EUS plays a prominent role.

PMID- 15555963
TI  - The impact of aviation-based teamwork training on the attitudes of health-care
      professionals.
AB  - BACKGROUND: Both the Institute of Medicine and the Agency for Healthcare Research
      and Quality suggest patient safety can be enhanced by implementing aviation Crew
      Resource Management (CRM) in health care. CRM emphasizes six key areas: managing
      fatigue, creating and managing teams, recognizing adverse situations (red flags),
      cross-checking and communication, decision making, and performance feedback. This
      study evaluates participant reactions and attitudes to CRM training. STUDY
      DESIGN: From April 22, 2003, to December 11, 2003, clinical teams from the trauma
      unit, emergency department, operative services, cardiac catheterization
      laboratory, and administration underwent an 8-hour training course. Participants
      completed an 11-question End-of-Course Critique (ECC), designed to assess the
      perceived need for training and usefulness of CRM skill sets. The Human Factors
      Attitude Survey contains 23 items and is administered on the same day both pre-
      and posttraining. It measures attitudinal shifts toward the six training modules
      and CRM. RESULTS: Of the 489 participants undergoing CRM training during the
      study period, 463 (95%) completed the ECC and 338 (69%) completed the Human
      Factors Attitude Survey. The demographics of the group included 288 (59%) nurses
      and technicians, 104 (21%) physicians, and 97 (20%) administrative personnel.
      Responses to the ECC were very positive for all questions, and 95% of respondents
      agreed or strongly agreed CRM training would reduce errors in their practice.
      Responses to the Human Factors Attitude Survey indicated that the training had a
      positive impact on 20 of the 23 items (p < 0.01). CONCLUSIONS: CRM training
      improves attitudes toward fatigue management, team building, communication,
      recognizing adverse events, team decision making, and performance feedback.
      Participants agreed that CRM training will reduce errors and improve patient
      safety.

PMID- 15555964
TI  - Recurrent disease after limited parathyroidectomy for sporadic primary
      hyperparathyroidism.
AB  - BACKGROUND: Limited parathyroidectomy guided by intraoperative parathyroid
      hormone (PTH) assay (QPTH) is highly successful (97% to 99%) in predicting
      postoperative eucalcemia, usually with less extensive dissection when compared
      with bilateral neck exploration. Because fewer glands are excised when resection
      is guided by QPTH as opposed to resection guided by gland size, a higher
      recurrence rate may occur. Recurrence rate after bilateral neck exploration is
      0.4% to 5%, but frequency of recurrence after limited parathyroidectomy is
      unknown. This study reports outcomes of this operative approach in sporadic
      primary hyperparathyroidism. STUDY DESIGN: Four-hundred twenty-three patients
      with sporadic primary hyperparathyroidism undergoing limited parathyroidectomy,
      followed 6 months or more or considered operative failures, were studied. In most
      patients, calcium and PTH levels were measured immediately after operation, and
      then at 2 and 6 months and yearly intervals. Operative failure is defined as
      hypercalcemia and high PTH within 6 months after operation, and recurrent
      hyperparathyroidism is hypercalcemia and elevated PTH occurring after a
      successful parathyroidectomy. Recurrence distributions were estimated using
      Kaplan-Meier analysis. RESULTS: The success rate of limited parathyroidectomy is
      97% (412/423). Four-hundred six patients were eucalcemic over an average of 34
      months (median 27, range 6 to 118 months) of followup and recurrent
      hyperparathyroidism developed in 6 of 412 (1.5%). Estimated 5 years recurrence
      free rate was 97% (95% confidence interval, 91% to 99%). Earliest and latest
      recurrences were diagnosed at 24 and 83 months, respectively. QPTH results did
      not predict any recurrence. Overall success rate was achieved, with multiple
      gland resections performed in only 3% of patients. CONCLUSIONS: Recurrence rate
      after limited parathyroidectomy is similar to rates reported after bilateral neck
      exploration. Parathyroidectomy guided by QPTH is successful not only in resolving
      hypercalcemia in the short term, but also in providing longterm eucalcemia.

PMID- 15555967
TI  - Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy:
      effect of clinical node status at presentation.
AB  - BACKGROUND: Both neoadjuvant chemotherapy and selective sentinel lymphadenectomy
      (SSL) are increasingly being used in treating primary breast cancer. It is
      important to determine whether SSL can be used after neoadjuvant chemotherapy and
      whether clinical node status at presentation affects accuracy of SSL. STUDY
      DESIGN: Between 1995 and 2003, 53 evaluable cases of invasive breast cancer were
      treated with neoadjuvant chemotherapy followed by SSL and completion axillary
      node dissection. The accuracy of SSL and the number of failed SSLs were assessed
      in the entire group and in the subset that were clinically node positive at
      presentation. RESULTS: The sensitivity of SSL was 96%, the negative predictive
      value was 96%, and the sentinel node identification rate was 94%. Of the 53
      evaluable patients, 23 had clinically node-positive disease at presentation (43%)
      and the remainder were clinically node negative (57%). Of the successfully
      completed SSL, the status of the sentinel lymph node corresponded to that of
      overall axillary status in 49 of 50 patients (accuracy rate 98%). Two of the 23
      patients with clinically node-positive disease at presentation had unsuccessful
      SSL. Of the remaining 21 patients with a clinically positive axilla before
      systemic therapy, a false-negative SSL result occurred in 1 patient (accuracy
      95%, sensitivity 91%). CONCLUSIONS: Selective sentinel lymphadenectomy after
      neoadjuvant chemotherapy is both feasible and accurate. Although early reports
      found a lower performance of SSL after neoadjuvant chemotherapy, this study
      suggests reevaluation of the current practice of full axillary lymph node
      dissection in this setting, particularly in those patients who are clinically
      node negative at presentation.

PMID- 15555968
TI  - Surgical robotics: impact of motion scaling on task performance.
AB  - BACKGROUND: Robotic systems have been shown to enhance surgical dexterity, and
      the advantage has been hypothesized to result from the removal of tremor and
      addition of motion scaling. But these purported gains over traditional
      laparoscopic instrumentation have not been quantified. This study was designed to
      compare the surgical accuracy between conventional laparoscopic instruments and a
      robotic surgical system and evaluate the importance of tremor filtration (TF) and
      motion scaling (MS) in these robotic systems. STUDY DESIGN: Fifteen participants
      with no previous surgical experience were enrolled. To simulate microsurgical
      techniques, a 29-gauge needle was used to puncture the center of 6 microscopic
      archery targets (circle diameters 0.5, 1.5, and 2.5 mm). The robotic system was
      configured to three different degrees of MS and compared with the unassisted
      laparoscopic platforms in accuracy. RESULTS: Accuracy with robotic assistance
      with TF alone (1:1 MS) was not significantly different from unassisted
      laparoscopic control. Both moderate (2.5:1) and fine (7:1) MS significantly
      improved accuracy over traditional laparoscopic control (p < 0.001 for both).
      Robotic assistance with MS equalized the performance of both hands (p = 0.03) in
      precision, and manual laparoscopy demonstrated no statistical difference in
      handedness (p = 0.80). CONCLUSIONS: Motion scaling, rather than tremor
      filtration, plays the major role in the enhanced accuracy seen in robotic
      surgical systems. Robotic assistance with MS significantly improved accuracy
      above laparoscopic instruments alone and robotic assistance with tremor
      filtration alone. MS also creates ambidexterity in an otherwise unidextrous
      population, optimizing the surgeon's ability to undertake tasks requiring
      microsurgical accuracy.

PMID- 15555969
TI  - Early experience with retrievable inferior vena cava filters in high-risk trauma
      patients.
AB  - BACKGROUND: This study describes the use of retrievable IVC filters in a select
      group of trauma patients at high risk for deep vein thrombosis (DVT) and
      pulmonary embolism (PE). STUDY DESIGN: Retrievable IVC filters were placed in
      selected trauma patients who met high-risk criteria for deep vein thrombosis and
      PE according to institutional clinical management guidelines. All filters were
      placed percutaneously in the interventional radiology suite. Indications for
      filter placement were based on injury complex, weight-bearing status, and
      contraindications to enoxaparin or pneumatic compression devices. IVC filters
      were either removed or maintained. RESULTS: Retrievable IVC filters were placed
      in 35 patients after blunt trauma. Twenty-six patients (74%) sustained at least
      one orthopaedic injury; 17 patients (49%) were diagnosed with a pelvis fracture.
      Activity was limited to bed rest or spinal precautions in 18 patients (51%).
      Enoxaparin was contraindicated in 32 patients (91%) and injuries precluded the
      use of pneumatic compression devices in 11 (31%). IVC filters were removed in 18
      patients (51%), with no reported complications. Patients with orthopaedic
      injuries and pelvis fractures were less likely to have their filters maintained
      (p = 0.040). CONCLUSIONS: Retrievable IVC filters offer a versatile option for
      prophylaxis in trauma patients at high risk for PE. Filter retrieval potentially
      spares the longterm complications of permanent filters in younger trauma
      patients. Retrievable filters warrant consideration in patients who meet high
      risk criteria for deep vein thrombosis or PE who cannot receive effective
      mechanical prophylaxis and in whom contraindications to anticoagulation are
      expected to be temporary.

PMID- 15555970
TI  - The special injury pattern in terrorist bombings.
AB  - BACKGROUND: The destructive human consequences of terrorist bombing always
      challenge the medical system in diagnosis, decision making, and patient
      management. This injury is produced by multiple injury mechanisms, and departs
      from the conventional description of trauma complexity. Our objective was to
      characterize and compare terror-bombing victims with casualties of all other
      kinds of trauma, and to validate the existence of a different, more complex,
      injury pattern. STUDY DESIGN: A retrospective cohort study was conducted of
      patient records from October 2000 through June 2003 in the Israeli National
      Trauma Registry. All were categorized as victims of terrorist bombings or of
      nonterror-related trauma. Analysis included age, gender, Injury Severity Score,
      Glasgow Coma Scale, admission blood pressure, injury complexity, surgical
      interventions, intensive care and hospital lengths of stay, in-hospital
      mortality, and disposition. This analysis was extended to Injury Severity Score
      subgroups. RESULTS: Victims of terrorist bombings (n = 906) were compared with
      55,033 casualties of nonterror-related trauma. Bombing resulted in significantly
      different injury complexity, increased severity, and with more body regions
      involved. Significantly enhanced use of intensive care, prolonged hospital stay,
      more surgical interventions, and increased hospital mortality are characteristic
      of these patients. CONCLUSIONS: Terrorist bombings inflict injury of a distinctly
      different pattern than other means of trauma. The simultaneous combination of
      different injury mechanisms in explosions results in a multidimensional injury
      pattern and a complicated clinical course. Hospital preparedness and medical team
      awareness to the unique nature of the injuries are mandatory for improving the
      outcomes of these patients.

PMID- 15555971
TI  - Adenocarcinoma of the gastric cardia: what is the optimal surgical approach?
AB  - BACKGROUND: The incidence of adenocarcinoma of the gastric cardia is rising in
      Western countries. This study evaluates prognostic factors associated with
      surgical management of this cancer. STUDY DESIGN: Medical records of consecutive
      patients with gastric cardial cancer treated by surgical resection from 1991
      through 2001 were reviewed. Survival was analyzed using the Kaplan-Meier method.
      Prognostic factors were evaluated using log-rank test and Cox regression. Mean
      followup period was 34 months. RESULTS: Eighty-two patients met study inclusion
      criteria. Median patient age was 65 years (range 86 to 22). Fifty-nine (72%)
      patients had type II tumors and 23 (28%) patients had type III tumors, according
      to the Siewert classification for gastroesophageal junction tumors. Twenty-seven
      (33%) patients underwent total esophagectomy, 24 (29%) patients underwent
      extended gastrectomy with thoracotomy, and 31 (38%) patients underwent extended
      gastrectomy without thoracotomy. Overall postoperative 5-year survival rate was
      30%. On multivariate analysis, patient age 65 years and older, absence of lymph
      node metastasis, and R0 resection emerged as factors independently associated
      with improved postoperative survival. Frequency with which proximal resection
      margin was infiltrated with cancer was a function of gross margin length and T
      stage. Proximal gross margin length of at least 6 cm was required to achieve a
      microscopically negative proximal margin for T3 and T4 cancers. CONCLUSIONS:
      Achieving R0 resection should be the goal of surgical therapy for the gastric
      cardial cancer. The surgical approach should be tailored to individual patients
      to achieve this goal.

PMID- 15555972
TI  - Neurobiologic changes in the hypothalamus associated with weight loss after
      gastric bypass.
AB  - BACKGROUND: Effects of Roux-en-Y gastric bypass (RYGB) on hypothalamic food
      intake regulation have not been investigated. The hypothalamic arcuate nucleus
      (ARC) and the magnocellular (m) and parvocellular (p) parts of the
      paraventricular nucleus (PVN) regulate hunger and satiety, and are under control
      of the orexigenic neuropeptide Y (NPY), and the anorexigenic alpha-melanocyte
      stimulating hormone (alpha-MSH) and serotonin (5-HT). We hypothesized that after
      RYGB, weight loss is associated with hypothalamic down regulation of NPY and up
      regulation of 5-HT and alpha-MSH. STUDY DESIGN: Obesity was induced in 12 Sprague
      Dawley rats using a high-energy diet for 7 weeks, and then the rats were divided
      into three groups (n = 4/group): RYGB, sham-operated pair-fed (PF), and sham
      operated ad libitum (obese control). Ten days after operation,
      immunohistochemical quantification of NPY, alpha-MSH, and 5-HT(1B)-receptors in
      ARC and PVN was performed. Data were analyzed using ANOVA and Tukey's test.
      RESULTS: Body weight decreased in RYGB (417 +/- 21 g; mean +/- SE) and in PF (436
      +/- 14 g) rats 10 days after operation compared with obese control rats (484 +/-
      15 g; p < 0.05 for each comparison). NPY in ARC, pPVN, and mPVN decreased by 43%,
      43%, and 61%, respectively in RYGB and by 55%, 42%, and 71% in PF, respectively,
      compared with obese controls (p < 0.05 for each pairwise comparison). RYGB versus
      PF did not show differences. alpha-MSH in ARC, pPVN and mPVN increased by 35%,
      175%, and 67%, respectively in RYGB and by 29%, 162%, and 116% in PF,
      respectively, compared with obese controls (each p < 0.05). In mPVN, alpha-MSH
      significantly decreased by 23% in RYGB versus PF (p < 0.05). 5-HT-(1B)-receptor
      in pPVN increased by 58% in RYGB and by 26% in PF, compared with obese controls
      (p < 0.05). Compared with obese controls, 5HT-(1B)-receptor in mPVN increased by
      39% in RYGB (p < 0.05) and by 9% in PF (p > 0.05). An increase of 5-HT-(1B)
      receptor in pPVN and mPVN occurred in RYGB versus PF (p < 0.05). CONCLUSIONS:
      Obese rats that undergo weight loss after RYGB demonstrate changes in
      hypothalamic down regulation of NPY and up regulation of alpha-MSH and serotonin.

PMID- 15555974
TI  - The timing of elective colectomy in diverticulitis: a decision analysis.
AB  - BACKGROUND: Determining the optimal strategy for elective colectomy in patients
      with diverticular disease involves a balance of the morbidity, mortality, costs,
      and quality of life associated with both elective and expectant management. We
      used decision and cost analysis to simulate the clinical and economic outcomes
      after recovery from an episode of nonsurgically treated diverticulitis to
      determine the preferable management strategy. STUDY DESIGN: A Markov model was
      constructed to evaluate lifetime risks of death and colostomy, care costs, and
      quality of life associated with elective colectomy after subsequent episodes of
      diverticulitis. The analysis was from the payer's perspective, using hypothetical
      cohorts of 35- and 50-year-old patients who recovered from a nonsurgically
      treated diverticulitis episode. Probabilities of clinical events and costs for
      the base-case analysis were derived from a large cohort using a statewide
      administrative database and published estimates. RESULTS: Performing colectomy
      after the fourth rather than the second episode in patients older than 50 years
      resulted in 0.5% fewer deaths, 0.7% fewer colostomies, and saved US 1,035 dollars
      per patient. In younger patients, performing colectomy after the fourth episode
      compared with the first episode resulted in 0.1% fewer deaths, 2% fewer
      colostomies, and saved US 5,429 dollars per patient. Expectant management through
      three recurrent episodes with elective colectomy after the fourth episode was the
      dominant strategy across the full range of the variables tested in the
      sensitivity analysis compared with earlier intervention. CONCLUSIONS: This study
      suggests that expectant management is associated with lower rates of death and
      colostomy and is cost-saving for both younger and older patients.

PMID- 15555973
TI  - Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse
      model of chronic cigarette smoke exposure.
AB  - BACKGROUND: Cigarette smoking and pulmonary emphysema are strongly associated
      with abdominal aortic aneurysms (AAAs), but the biologic mechanisms linking these
      conditions are undefined. STUDY DESIGN: To determine if exposure to cigarette
      smoke influences formation and growth of experimental AAAs, 129/SvEv mice were
      acclimated to daily cigarette smoke exposure for 2 weeks followed by transient
      elastase perfusion of the abdominal aorta to induce aneurysmal degeneration.
      Smoking was continued for intervals of either 2 or 12 weeks (8 mice per group).
      Nonsmoking 129/SvEv controls (n = 29) underwent elastase perfusion and followup
      evaluation at the same time intervals. In all animals, abdominal aortic diameter
      (AD) was measured to determine interval increases in AD (Delta AD), with AAAs
      defined as a Delta AD > 100%. RESULTS: Preperfusion and immediate postperfusion
      ADs were not significantly different between experimental groups. Aneurysmal
      dilatation was present 2 weeks after elastase perfusion in both smoking mice and
      nonsmoking controls, with no significant difference in final AD (mean +/- SEM:
      smoking, 1.23 +/- 0.11 mm versus nonsmoking, 1.22 +/- 0.05 mm). There were also
      no differences in the overall extent of aortic dilatation (Delta AD smoking, 136
      +/- 24% versus nonsmoking, 138 +/- 10%), or the incidence of AAAs (smoking, 75%
      versus nonsmoking, 79%). Although all animals had developed AAAs by 12 weeks
      after elastase perfusion, the overall extent of aortic dilatation was 50% greater
      in smoking mice compared with nonsmoking controls (Delta AD smoking, 204 +/- 23%
      versus nonsmoking, 135 +/- 17%; p < 0.05). CONCLUSIONS: Short-term exposure to
      cigarette smoke did not alter initial development of experimental AAAs, but
      chronic smoke exposure was associated with a substantial increase in the late
      progression of aneurysmal dilatation. This novel combination of in vivo
      experimental models offers a new approach to investigate mechanisms by which
      cigarette smoking promotes aneurysmal degeneration.

PMID- 15555975
TI  - Is there a role for selective neck dissection after chemoradiation for head and
      neck cancer?

PMID- 15555976
TI  - What's new in colon and rectal surgery.

PMID- 15555977
TI  - What's new in orthopaedic surgery.

PMID- 15555978
TI  - Attending, house officer, and medical student perceptions about teaching in the
      third-year medical school general surgery clerkship.
AB  - BACKGROUND: There has been declining interest in surgery among medical students
      and one reason might be the third-year clerkship experience. The aim of this
      study was to clarify the perceptions and expectations of attendings, residents,
      and medical students on the clerkship experience. STUDY DESIGN: A survey was
      distributed to all general surgery attendings, the entire general surgery house
      staff, and an entire third year medical school class inclusive of the 2001-2002
      academic year at a single institution. Statistic analysis consisted of chi-square
      and Kruskal-Wallis-ANOVA on ranks with Dunn's test for multiple comparisons. A p
      < 0.05 was significant. RESULTS: Responses were obtained from 59 attending
      surgeons (50%), 38 surgical residents (32%), and 107 medical students (66%). Of
      this student cohort, 35% were planning to choose a surgical specialty as a
      career. Agreement was high among faculty, students, and residents about factors
      considered important in evaluation, expectations of skills, and level of skills
      needed before the clerkship. Medical students desired more hours of instruction,
      believed they performed fewer procedures per week, and thought that feedback was
      poor compared with the opinions of faculty and residents (p < 0.002). Nearly 50%
      of medical students believed they were an inconvenience to the service; 30% of
      house officers and 27% of faculty (p < 0.001) believed this also. Almost all
      faculty and residents, however, wanted medical students on the service (> 95%).
      Faculty believed residents did a better job teaching than either the students or
      residents themselves did (p < 0.001), and students thought that residents were
      the primary source of education in patient care. CONCLUSIONS: Considerable
      differences exist between faculty, surgical resident, and medical student
      perceptions and expectations of medical student education. Structured direct
      faculty contact, definition of medical student roles on the surgical team, and
      more consistent feedback can be rapidly improved.

PMID- 15555979
TI  - Update on open repair of abdominal aortic aneurysms: the challenges for
      endovascular repair.

PMID- 15555980
TI  - Minimally invasive breast surgery.

PMID- 15555981
TI  - The role of Claude Bernard and others in the discovery of Horner's syndrome.

PMID- 15555982
TI  - The National Practitioner Data Bank: structure and function.

PMID- 15555983
TI  - Retrograde intussusception after Roux-en-Y gastric bypass surgery.

PMID- 15555984
TI  - Gastric trichobezoar and Rapunzel syndrome.

PMID- 15555985
TI  - Complete esophageal diversion: a simplified, easily reversible technique.

PMID- 15555986
TI  - Total pancreatectomy with intraportal auto-islet transplantation using a
      temporarily exteriorized omental vein.

PMID- 15555987
TI  - Use of a statewide administrative database in assessing a regional trauma system.

PMID- 15555989
TI  - Intraoperative monitoring of kinetic total serum calcium levels in primary
      hyperparathyroidism operation.

PMID- 15555990
TI  - Defining palliation in patients undergoing gastrectomy for gastric cancer.

PMID- 15555993
TI  - Prana Biotechnology, Limited: metal attenuation in the treatment of
      neurodegenerative disease.

PMID- 15555994
TI  - Engineering switches, genetically.
AB  - Ostermeier, Guntas, and Mitchel describe a new approach to design enzymes that
      are allosterically regulated by an unrelated ligand . The resulting protein,
      constructed by nonhomologous recombination and genetic screens, displays switch
      like behavior.

PMID- 15555995
TI  - Targeting alpha-synuclein in Parkinson's disease.
AB  - alpha-Synuclein aggregation into fibrils is associated with the pathogenesis of
      Parkinson's disease (PD). Li et al. provide strong evidence that rifampicin
      interacts with alpha-synuclein and inhibits its fibrillization. Rifampicin could
      be a promising candidate for therapeutic application for PD.

PMID- 15555996
TI  - Microbe manufacturers of semiconductors.
AB  - Synthesis of cadmium sulfide (CdS) semiconductor nanoparticles within a
      prokaryotic organism is reported for the first time by Sweeney et al. This paper
      demonstrates the utility of microorganisms to perform chemistries outside the
      scope of their "normal" metabolism and offers an environmentally benign synthesis
      of CdS nanoparticles.

PMID- 15555997
TI  - Finding their groove; bifunctional molecules arrest growth of cancer cells.
AB  - In this issue, Dickinson et al. describe an exciting advance in the search for
      inhibitors of transcription that function well in cells . The authors screen for
      small molecules that selectively damage DNA and identify a histone gene as a
      potential new target for cancer therapeutic development.

PMID- 15555998
TI  - A molecular switch created by in vitro recombination of nonhomologous genes.
AB  - We have created a molecular switch by the in vitro recombination of nonhomologous
      genes and subjecting the recombined genes to evolutionary pressure. The gene
      encoding TEM1 beta-lactamase was circularly permuted in a random fashion and
      subsequently randomly inserted into the gene encoding Escherichia coli maltose
      binding protein. From this library, a switch (RG13) was identified in which its
      beta-lactam hydrolysis activity was compromised in the absence of maltose but
      increased 25-fold in the presence of maltose. Upon removal of maltose, RG13's
      catalytic activity returned to its premaltose level, illustrating that the
      switching is reversible. The modularity of RG13 was demonstrated by increasing
      maltose affinity while preserving switching activity. RG13 gave rise to a novel
      cellular phenotype, illustrating the potential of molecular switches to rewire
      the cellular circuitry.

PMID- 15555999
TI  - Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase
      independent mechanism.
AB  - Most patients with the pediatric neurodegenerative disease spinal muscular
      atrophy have a homozygous deletion of the survival motor neuron 1 (SMN1) gene,
      but retain one or more copies of the closely related SMN2 gene. The SMN2 gene
      encodes the same protein (SMN) but produces it at a low efficiency compared with
      the SMN1 gene. We performed a high-throughput screen of approximately 47,000
      compounds to identify those that increase production of an SMN2-luciferase
      reporter protein, but not an SMN1-luciferase reporter protein. Indoprofen, a
      nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor,
      selectively increased SMN2-luciferase reporter protein and endogenous SMN protein
      and caused a 5-fold increase in the number of nuclear gems in fibroblasts from
      SMA patients. No other NSAIDs or COX inhibitors tested exhibited this activity.

PMID- 15556000
TI  - A flexible data analysis tool for chemical genetic screens.
AB  - High-throughput assays generate immense quantities of data that require
      sophisticated data analysis tools. We have created a freely available software
      tool, SLIMS (Small Laboratory Information Management System), for chemical
      genetics which facilitates the collection and analysis of large-scale chemical
      screening data. Compound structures, physical locations, and raw data can be
      loaded into SLIMS. Raw data from high-throughput assays are normalized using
      flexible analysis protocols, and systematic spatial errors are automatically
      identified and corrected. Various computational analyses are performed on tested
      compounds, and dilution-series data are processed using standard or user-defined
      algorithms. Finally, published literature associated with active compounds is
      automatically retrieved from Medline and processed to yield potential mechanisms
      of actions. SLIMS provides a framework for analyzing high-throughput assay data
      both as a laboratory information management system and as a platform for
      experimental analysis.

PMID- 15556001
TI  - Cross-catalytic replication of an RNA ligase ribozyme.
AB  - A self-replicating RNA ligase ribozyme was converted to a cross-catalytic format
      whereby two ribozymes direct each other's synthesis from a total of four
      component substrates. Each ribozyme binds two RNA substrates and catalyzes their
      ligation to form the opposing ribozyme. The two ribozymes are not perfectly
      complementary, as is the case for replicating nucleic acid genomes in biology.
      Rather, the ribozymes contain both template elements, which are complementary,
      and catalytic elements, which are identical. The specificity of the template
      interactions allows the cross-catalytic pathway to dominate over all other
      reaction pathways. As the concentration of the two ribozymes increases, the rate
      of formation of additional ribozyme molecules increases, consistent with the
      overall autocatalytic behavior of the reaction system.

PMID- 15556002
TI  - Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils.
AB  - The aggregation of alpha-synuclein in dopaminergic neurons of the substantia
      nigra is a critical step in the pathogenesis of Parkinson's disease. We show that
      the antibiotic rifampicin inhibited alpha-synuclein fibrillation and
      disaggregated existing fibrils in a concentration-dependent manner. Size
      exclusion chromatography data indicated that rifampicin stabilized alpha
      synuclein as both a monomer and soluble oligomers comprised of partially folded
      alpha-synuclein. Experiments using aged samples of rifampicin indicated that the
      most active species in inhibiting fibrillation and disaggregating fibrils is an
      oxidation product of rifampicin, which was confirmed in experiments under
      anaerobic conditions. These results indicate that rifampicin-mediated inhibition
      of alpha-synuclein fibrillation and disaggregation of fibrils involves
      preferential stabilization of monomeric and soluble oligomeric forms, and that
      rifampicin potentially may have therapeutic application for Parkinson's disease.

PMID- 15556003
TI  - Discovering disease-associated enzymes by proteome reactivity profiling.
AB  - Proteomics aims to identify new markers and targets for the diagnosis and
      treatment of human disease. To realize this goal, methods and reagents are needed
      to profile proteins based on their functional properties, rather than mere
      abundance. Here, we describe a general strategy for synthesizing and evaluating
      structurally diverse libraries of activity-based proteomic probes. Quantitative
      screening of probe-proteome reactions coupled with bioinformatic analysis enabled
      the selection of a suite of probes that exhibit complementary protein reactivity
      profiles. This optimal probe set was applied to discover several enzyme
      activities differentially expressed in lean and obese (ob/ob) mice.
      Interestingly, one of these enzymes, hydroxypyruvate reductase, which was 6-fold
      upregulated in ob/ob livers, participates in the conversion of serine to glucose,
      suggesting that this unusual metabolic pathway may contribute to gluconeogenesis
      selectively in states of obesity.

PMID- 15556004
TI  - Hybrid nonribosomal peptide-polyketide interfaces in epothilone biosynthesis:
      minimal requirements at N and C termini of EpoB for elongation.
AB  - Epothilone (Epo) D, an antitumor agent currently in clinical trials, is a hybrid
      natural product produced by the combined action of nonribosomal peptide
      synthetases (NRPS) and polyketide synthases (PKS). In the epothilone biosynthetic
      pathway, EpoB, a 165 kDa NRPS is inserted into an otherwise entirely PKS assembly
      line, forming two hybrid NRPS-PKS interfaces. In light of the terminal linker
      effect previously identified in PKS, the N- and C-terminal sequences of EpoB were
      examined for their roles in propagating the incipient natural product. Eight
      amino acid residues at EpoB C terminus, in which six are positively charged, were
      found to be a key component of the C-terminal linker effect. A minimal sequence
      of 56 residues at EpoB N terminus was required for elongating the acetyl group
      from the acyl carrier protein (ACP) of EpoA to form methylthiazolyl-S-EpoB.

PMID- 15556005
TI  - bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial
      symbiont of the marine bryozoan Bugula neritina.
AB  - "Candidatus Endobugula sertula," the uncultivated bacterial symbiont of Bugula
      neritina, is the proposed source of the bryostatin family of anticancer
      compounds. We cloned a large modular polyketide synthase (PKS) gene complex from
      "Candidatus Endobugula sertula" and characterized one gene, bryA, which we
      propose is responsible for the initial steps of bryostatin biosynthesis. Typical
      PKS domains are present. However, acyltransferase domains are lacking in bryA,
      and beta-ketoacyl synthase domains of bryA cluster with those of PKSs with
      discrete, rather than integral, acyltransferases. We propose a model for
      biosynthesis of the bryostatin D-lactate starter unit by the bryA loading module,
      utilizing atypical domains homologous to FkbH, KR, and DH. The bryA gene product
      is proposed to synthesize a portion of the pharmacologically active part of
      bryostatin and may be useful in semisynthesis of clinically useful bryostatin
      analogs.

PMID- 15556006
TI  - Bacterial biosynthesis of cadmium sulfide nanocrystals.
AB  - Semiconductor nanocrystals, which have unique optical and electronic properties,
      have potential for applications in the emerging field of nanoelectronics. To
      produce nanocrystals cheaply and efficiently, biological methods of synthesis are
      being explored. We found that E. coli, when incubated with cadmium chloride and
      sodium sulfide, have the capacity to synthesize intracellular cadmium sulfide
      (CdS) nanocrystals. The nanocrystals are composed of a wurtzite crystal phase
      with a size distribution of 2-5 nm. Nanocrystal biosynthesis increased about 20
      fold in E. coli cells grown to stationary phase compared to late logarithmic
      phase. Our results highlight how different genetic and physiological parameters
      can enhance the formation of nanocrystals within bacterial cells.

PMID- 15556007
TI  - Production of 8'-halogenated and 8'-unsubstituted novobiocin derivatives in
      genetically engineered streptomyces coelicolor strains.
AB  - In the present study, we produced a hybrid antibiotic, carrying a chlorine atom
      instead of a methyl group at position 8 of the aminocoumarin moiety of
      novobiocin. This compound was not accessible by conventional gene
      inactivation/gene expression experiments due to difficulties in the genetic
      manipulation of the novobiocin producer Streptomyces spheroides. However, the
      desired compound was obtained after modification of the novobiocin biosynthetic
      gene cluster by using lambda-Red-mediated recombination in Escherichia coli,
      followed by integration of the resulting modified cosmid into the phiC31
      attachment site of Streptomyces coelicolor and coexpression of the halogenase Clo
      hal of clorobiocin biosynthesis. The halogenase BhaA, responsible for
      chlorination of tyrosyl moieties of the glycopeptide antibiotic balhimycin, was
      unable to functionally replace the halogenase Clo-hal, suggesting that the two
      enzymes have different substrate specificities.

PMID- 15556008
TI  - Enhanced macrocyclizing activity of the thioesterase from tyrocidine synthetase
      in presence of nonionic detergent.
AB  - Macrocyclization carried out by thioesterase domains of multimodular nonribosomal
      peptide synthetases (NRPSs) is a key step in the biosynthesis of many
      biologically active peptides. The thioesterase excised from tyrocidine synthetase
      is a versatile macrocyclization catalyst and a useful tool for chemoenzymatic
      synthesis of diverse cyclic peptides. However, its utility is limited by its
      short lifetime of catalytic activity as well as significant flux of the acyl
      enzyme intermediate to hydrolysis. The addition of Brij 58, a nonionic detergent,
      above the critical micelle concentration, has dramatic effects on enzyme
      activity: catalytic activity is extended to >60 min and the rate of cyclization
      (but not hydrolysis) increases 6-fold, resulting in a net 150- to 300-fold
      increase in cyclic product yields. This enhanced activity allowed enzymatic
      macrocyclization of a solid phase library of tyrocidine decapeptides to identify
      acceptable substitutions at the Orn9 position which had previously been
      inaccessible for diversification.

PMID- 15556009
TI  - Arresting cancer proliferation by small-molecule gene regulation.
AB  - A small library of pyrrole-imidazole polyamide-DNA alkylator (chlorambucil)
      conjugates was screened for effects on morphology and growth characteristics of a
      human colon carcinoma cell line, and a compound was identified that causes cells
      to arrest in the G2/M stage of the cell cycle. Microarray analysis indicates that
      the histone H4c gene is significantly downregulated by this polyamide. RT-PCR and
      Western blotting experiments confirm this result, and siRNA to H4c mRNA yields
      the same cellular response. Strikingly, reduction of H4 protein by >50% does not
      lead to widespread changes in global gene expression. Sequence-specific
      alkylation within the coding region of the H4c gene in cell culture was confirmed
      by LM-PCR. The compound is active in a wide range of cancer cell lines, and
      treated cells do not form tumors in nude mice. The compound is also active in
      vivo, blocking tumor growth in mice, without obvious animal toxicity.

PMID- 15556010
TI  - Estimation of time since death by heat-flow Finite-Element model. Part I: method,
      model, calibration and validation.
AB  - The determination of the time since death which often represents the presumed
      time of an offence plays an important role in medico-legal practice. In the early
      postmortem phase analyses of postmortem cooling provide the most accurate
      estimates. Empirical models of postmortem cooling are methodically restricted to
      standard conditions while heat flow models can in principle be applied to any
      complex cooling situations. The main problem having so far prevented heat flow
      models from being used in practice was the difficulty of solving the heat
      transfer equation for complex geometrical, initial and boundary conditions. This
      problem is now overcome by using the Finite-Element-Method as a numerical
      procedure. The study presents a three-dimensional Finite-Element-Model of the
      human body containing various tissue compartments with different thermal tissue
      properties. The initial temperature field is modelled inhomogeneously with a
      temperature gradient between body core and shell. Heat loss by conduction,
      convection and radiation as well as heat gain by supravital activity or
      irradiation from external sources can be simulated. One model parameter, the
      decrease rate of the supravital energy production, was calibrated and the model
      successfully validated using the experimentally verified empirical model by
      Marshall and Hoare.

PMID- 15556011
TI  - Biochemical background of ethanol-induced cold susceptibility.
AB  - The process of cooling is always associated with the depletion of energetic
      reserves and burning the ketone bodies covers the tissues' needs. Ethanol shows
      antiketonaemic effects changing the cellular redox potential, inhibiting beta
      oxidation of fatty acids, stimulating the release of insulin and inhibiting the
      release of its antagonist. The aim of the study was to determine whether the
      cooling process of the organism in the presence of ethanol intoxication may be
      related to inhibition of the physiological mechanism of ketogenesis induced by
      hypothermia. The study involved the 67 autopsy cases from 1996 to 2002, in which
      the circumstances of death indicated the effects of overcooling. This was
      confirmed on the basis of the data from the Prosecutor's Offices. Then, the
      chromatograms of autopsy blood alcohol determinations were analyzed and the
      acetone levels recorded. The analysis supported the hypothesis that the severity
      of ketosis is inversely proportional to the blood ethanol concentration.
      Furthermore, it demonstrated that signs of prolonged cold exposure were less
      frequently observed in unsober persons (frostbites, gastric hemorrhages).
      Increased sensitivity of intoxicated individuals to cold may be related not only
      to the dilation of the peripheral vessels, inhibition of shivering thermogenesis
      caused by muscle relaxation, central nervous system depression and behavioral
      factors but also to the antiketonaemic effects of ethanol.

PMID- 15556012
TI  - Effect of hypothermia on postmortem alterations in MAP2 immunostaining in the
      human hippocampus.
AB  - Ischemic neuronal injury induce degradation of microtubule-associated protein 2
      (MAP2). In addition to ischemia, postmortem brains show alterations in MAP2
      immunoreactivity in the hippocampus, suggesting that the factors inducing
      cytoskeletal disruption in postmortem brain are similar to those in ischemic
      brains. Hypothermia reduces the severity of ischemic injury including disruption
      of MAP2 in the hippocampus. However, whether hypothermia reduces postmortem
      changes of MAP2 was not clear. In this study, we evaluated the effect of
      hypothermia on postmortem degradation of MAP2 in the human hippocampus at various
      postmortem intervals using immunohistochemistry. In postmortem brains without
      hypothermia (the normothermic group), the locus of MAP2 immunoreactivity moved
      from the dendrites to the cell bodies prior to becoming undetectable with
      increasing postmortem interval, particularly in the CA1-subiculum region. On the
      other hand, the change in MAP2 immunoreactivity was remarkably attenuated in
      brains of death from cold (the hypothermic group). The present study demonstrated
      that MAP2 disruption is remarkable in the CA1-subiculum region of autopsied
      brains and that hypothermia reduces the postmortem change of MAP2, as observed in
      ischemic brain. Therefore, immunostaining of MAP2 in the hippocampus could be
      used to diagnose hypothermia.

PMID- 15556013
TI  - DNA typing of bone specimens--the potential use of the profiler test as a tool
      for bone identification.
AB  - Twenty-six bone DNA identification cases are described. The postmortem periods of
      the studied remains ranged from three days to over 30 years, and the locations
      where the remains were found varied resulting in a variety of postmortem
      conditions. Nuclear DNA typing using an AmpFLSTR Profiler kit and mitochondrial
      DNA (mtDNA) typing of hypervariable regions 1 and 2 (HV1 and HV2) in a control
      region were performed both with decalcified and non-treated bone powder samples.
      Decalcification was shown to improve the success of DNA typing. The nucleotide
      sequences of the HV1 and HV2 regions were successfully determined in all cases
      examined. Nuclear DNA typing was very successful, more than half of the loci were
      typed during multiple amplifications (10 loci in one reaction) in 23 cases.
      Polymerase chain reaction (PCR) inhibition was observed in five cases including
      three samples that were found buried in soil. This inhibitory effect was
      identified as the result of unbalanced multiple PCR during the profiler test.
      These results revealed that DNA typing targeting nuclear DNA is a potentially
      powerful tool for bone identification.

PMID- 15556014
TI  - Immunohistochemical study of rat spermatogenesis after toluene-inhalation.
AB  - After prolonged toluene-inhalation (for 20 days) at the common abuse density
      (1500 ppm for 4 h per day), the effect of toluene on spermatogenesis in rats was
      investigated. Body weight was significantly decreased in the toluene group (P <
      0.05). However, the weights of the testis and epididymis were maintained. To
      confirm whether the toluene-inhalation influences testis and epididymis as a
      stress factor; anti-70kD heat-shock protein (HSP70) and c-fos gene product (c
      Fos) were observed. To observe the change of the cell division and the
      proliferation in spermatogenesis, proliferating cell nuclear antigen (PCNA) were
      stained immunohistochemically, and apoptosis was also detected. There was no
      positive immunoreactivity for HSP70 or c-Fos. There was no significant difference
      in the PCNA-expression in both groups. It was considered that toluene-inhalation
      did not have a clear influence in the division of spermatogonium and
      spermatocytes. On in situ apoptosis detection, slightly enhanced signals were
      observed in the toluene-inhalation groups. This might have some influence on
      meiosis from spermatocyte to spermatid. However, in toluene-inhalation rats
      exposed to a common abuse density, it was considered that spermatogenesis was
      well maintained and not apparently damaged.

PMID- 15556015
TI  - Fatal hypernatremia after using salt as an emetic--report of three autopsy cases.
AB  - Although a plethora of reports on life-threatening complications of salt emesis
      has been published since the early 1960s, salt is still used to induce emesis in
      cases of intoxication in the clinical as well as in the domestic setting. We
      report three cases of fatal hypernatremia after salt was used as an emetic. All
      fatalities were subjected to medico-legal autopsy at the Institute of Legal
      Medicine in Hamburg, Germany. In all cases, symptoms of cerebral damage such as
      seizures, fever and somnolence developed within hours after salt ingestion. All
      individuals were admitted to hospital before their deaths. Here, severe
      hypernatremia (up to 245 mmol/l) was detected, and all patients died under the
      clinical picture of cerebral edema despite intensive medical treatment. At
      autopsy, unspecific signs of a central regulatory failure were present. Histology
      revealed crenated red blood cells and few venous microthrombi in internal organs.
      Neuropathological investigations yielded no specific results but confirmed fatal
      cerebral edema and excluded other cerebral causes of death. Viewing the results
      of clinical and post-mortem investigations together, death could clearly be
      attributed to excessive salt intake in all cases.

PMID- 15556016
TI  - Sudden unexpected death of a 17-year-old male infected with the influenza virus.
AB  - We report a case of sudden unexpected death in a 17-year-old male student showing
      similar clinical background and pathological findings to Reye's syndrome. He was
      found following cardio-pulmonary arrest in his bed, and was immediately
      transferred to a hospital. However, resuscitation was not successful. He had a
      history of high fever of 38.3 degrees C, general malaise, myalgia, and
      gastrointestinal discomfort for the 2 days prior to his death, and an injection
      of pylazolon and medication comprising anti-emetics had been administered the day
      before he died. His biochemical findings showed almost normal levels of
      transaminase, electrolytes and protein fractions at the emergency room, but blood
      from the heart at autopsy revealed a high titer of the influenza A virus.
      Macroscopically, in addition to considerable fatty metamorphosis of the liver,
      concentric hypertrophy of the left ventricle, muscular bridge of left anterior
      descending artery, moderate coronary atherosclerosis, and mild downward
      displacement of the septal leaflet of the tricuspid valve were noted in the
      heart. Although panlobular microvesicular fatty infiltration of the liver was
      seen, deposition of lipid droplets was detected only in hepatocytes by frozen
      section of several organs. Serial sectioning of the epicardial coronary arteries
      showed about 50% stenosis at the distal site of the left circumflex artery, and
      diffuse interstitial fibrosis was evident in the bilateral ventricle and this was
      relatively severe for his age. In addition, the atrioventricular (AV) node artery
      showed severe narrowing just before entering the AV node, and downward
      displacement of the AV node with longitudinal elongation was also remarkable. We
      consider that the cause of death was sudden cardiac death rather than Reye's
      syndrome (RS), and that an arrhythmogenic event due to some preceding unusual
      cardiac lesions may have become overt due to the influenza infection and/or some
      related disorders. The present case would seem to suggest that a postmortem
      diagnosis of RS should be determined very carefully in cases of sudden death,
      even if the general circumstances would seem to be consistent with RS.

PMID- 15556017
TI  - Genetic polymorphisms at 13 STR loci in autochthonous Basques from the province
      of Alava (Spain).
AB  - In this study, allelic frequencies of the CODIS core short tandem repeat (STR)
      loci were estimated in a population sample consisting in 101 unrelated healthy
      autochthonous individuals from the Basque province of Alava (Northern Spain).
      Frequency distributions for all 13 STR loci were obtained using the AmpFlSTR
      Profiler Plus and AmpFlSTR COfiler amplification kits. The allelic frequencies
      generated were employed to calculate genetic and forensic useful parameters.

PMID- 15556018
TI  - Neural computations of decision utility.
AB  - How are decision alternatives represented in the primate brain? A recent study by
      Sugrue et al. sought to answer this question by integrating behavioral,
      computational and physiological methods in examining the choice patterns of
      monkeys placed in a dynamic foraging environment. They observed specific encoding
      of the relative value of alternatives by neurons in the parietal cortex,
      providing an important starting point for researchers interested in how value and
      probability are combined in the brain to arrive at decision outcomes.

PMID- 15556019
TI  - The puzzle of working memory for sign language.
AB  - Why is immediate-serial-recall (short-term memory) span consistently shorter for
      sign language than it is for speech? A new study by Boutla et al. shows that
      neither the length of signs, nor the formational similarity of signed digits, can
      account for the difference. Their results suggest instead that the answer lies in
      differences between the auditory and visual systems. At the same time, however,
      their results show that sign language and spoken language yield equivalent
      processing spans, suggesting that reliance on immediate-serial-recall measures in
      clinical and educational testing is misplaced.

PMID- 15556020
TI  - Attention and awareness in synchrony.
AB  - Interactions between functional areas are often considered to account for subtle
      aspects of cognitive functions, although direct experimental evidence is scarce.
      A recent study by Gross et al. relates the strength of synchrony between human
      parietal, frontal and occipital regions to the availability of attentional
      resources. These results support the current view that attention and awareness
      emerge from dynamic interactions in distributed networks.

PMID- 15556021
TI  - Core mechanisms in "theory of mind".
AB  - Our ability to understand the thoughts and feelings of other people does not
      initially develop as a theory but as a mechanism. The "theory of mind" mechanism
      (ToMM) is part of the core architecture of the human brain, and is specialized
      for learning about mental states. Impaired development of this mechanism can have
      drastic effects on social learning, seen most strikingly in the autistic spectrum
      disorders. ToMM kick-starts belief-desire attribution but effective reasoning
      about belief contents depends on a process of selection by inhibition. This
      selection process (SP) develops slowly through the preschool period and well
      beyond. By modeling the ToMM-SP as mechanisms of selective attention, we have
      uncovered new empirical phenomena. We propose that early "theory of mind" is a
      modular-heuristic process of domain-specific learning.

PMID- 15556022
TI  - Conceptual development and conversational understanding.
AB  - Children's understanding of the implications of conversation can influence their
      responses on tasks designed to measure conceptual development. These responses
      are in keeping with developmental changes in the ability to recognize and resolve
      ambiguity in communicative contexts, as shown, for example, in children's ability
      to compute "scalar implicatures". Examining steps children take to overcome
      difficulties in processing the relevant features of tasks and in correctly
      interpreting task instructions promise to illuminate mechanisms of conceptual
      development. We review recent research in this area, focussing on early knowledge
      of the appearance-reality distinction and knowledge of cosmological concepts.

PMID- 15556023
TI  - Conflict monitoring and anterior cingulate cortex: an update.
AB  - One hypothesis concerning the human dorsal anterior cingulate cortex (ACC) is
      that it functions, in part, to signal the occurrence of conflicts in information
      processing, thereby triggering compensatory adjustments in cognitive control.
      Since this idea was first proposed, a great deal of relevant empirical evidence
      has accrued. This evidence has largely corroborated the conflict-monitoring
      hypothesis, and some very recent work has provided striking new support for the
      theory. At the same time, other findings have posed specific challenges,
      especially concerning the way the theory addresses the processing of errors.
      Recent research has also begun to shed light on the larger function of the ACC,
      suggesting some new possibilities concerning how conflict monitoring might fit
      into the cingulate's overall role in cognition and action.

PMID- 15556024
TI  - Emergence of rhythm during motor learning.
AB  - Complex motor skill often consists of a fixed sequence of movements. Recent
      studies show that a stereotyped temporal pattern or rhythm emerges as we learn to
      perform a motor sequence. This is because the sequence is reorganized during
      learning as serial chunks of movements in both a sequence-specific and subject
      specific manner. On the basis of human imaging studies we propose that the
      formation of chunk patterns is controlled by the cerebellum, its posterior and
      anterior lobes contributing, respectively, to the temporal patterns before and
      after chunk formation. The motor rhythm can assist the motor networks in the
      cerebral cortex to control automatic movements within chunks and the cognitive
      networks to control non-automatic movements between chunks, respectively. In this
      way, organized motor skill can be performed automatically and flexibly.

PMID- 15556025
TI  - Emotions: from brain to robot.
AB  - Some robots have been given emotional expressions in an attempt to improve human
      computer interaction. In this article we analyze what it would mean for a robot
      to have emotion, distinguishing emotional expression for communication from
      emotion as a mechanism for the organization of behavior. Research on the
      neurobiology of emotion yields a deepening understanding of interacting brain
      structures and neural mechanisms rooted in neuromodulation that underlie emotions
      in humans and other animals. However, the chemical basis of animal function
      differs greatly from the mechanics and computations of current machines. We
      therefore abstract from biology a functional characterization of emotion that
      does not depend on physical substrate or evolutionary history, and is broad
      enough to encompass the possible emotions of robots.

PMID- 15556026
TI  - Growth and development the whole picture begins to emerge.

PMID- 15556027
TI  - Cytoskeletal elements in bacteria.
AB  - It has become clear recently that bacteria contain all of the cytoskeletal
      elements that are found in eukaryotic cells, demonstrating that the cytoskeleton
      has not been a eukaryotic invention, but evolved early in evolution. Several
      proteins that are involved in cell division, cell structure and DNA partitioning
      have been found to form highly dynamic ring structures or helical filaments
      underneath the cell membrane or throughout the length of the cell. These exciting
      findings indicate that several highly dynamic processes occur within prokaryotic
      cells, during growth or differentiation, that are vital for a wide range of
      cellular tasks.

PMID- 15556028
TI  - Spatial complexity of mechanisms controlling a bacterial cell cycle.
AB  - Cell cycle progression in Caulobacter is governed by a multilayered regulatory
      network linking chromosome replication with polar morphogenesis and cell
      division. Temporal and spatial regulation have emerged as the central themes,
      with the abundance, activity and subcellular location of key structural and
      regulatory proteins changing over the course of the cell cycle. An additional
      layer of complexity was recently uncovered, showing that each segment of the
      chromosome is located at a specific cellular position both during and after the
      completion of DNA replication, raising the possibility that this positioning
      contributes to temporal and spatial control of gene expression.

PMID- 15556029
TI  - Sporulation of Bacillus subtilis.
AB  - Differentiation of vegetative Bacillus subtilis into heat resistant spores is
      initiated by the activation of the key transcription regulator Spo0A through the
      phosphorelay. Subsequent events depend on the cell compartment-specific action of
      a series of RNA polymerase sigma factors. Analysis of genes in the Spo0A regulon
      has helped delineate the mechanisms of axial chromatin formation and asymmetric
      division. There have been considerable advances in our understanding of critical
      controls that act to regulate the phosphorelay and to activate the sigma factors.

PMID- 15556030
TI  - Cell polarity, intercellular signalling and morphogenetic cell movements in
      Myxococcus xanthus.
AB  - In Myxococcus xanthus morphogenetic cell movements constitute the basis for the
      formation of spreading vegetative colonies and fruiting bodies in starving cells.
      M. xanthus cells move by gliding and gliding motility depends on two polarly
      localized engines, type IV pili pull cells forward, and slime extruding nozzle
      like structures appear to push cells forward. The motility behaviour of cells
      provides evidence that the two engines are localized to opposite poles and that
      they undergo polarity switching. Several proteins involved in regulating polarity
      switching have been identified. The cell surface-associated C-signal induces the
      directed movement of cells into nascent fruiting bodies. Recently, the molecular
      nature of the C-signal molecule was elucidated and the motility parameters
      regulated by the C-signal were identified. From the effect of the C-signal on
      cell behaviour it appears that the C-signal inhibits polarity switching of the
      two motility engines. This establishes a connection between cell polarity,
      signalling by an intercellular signal and morphogenetic cell movements during
      fruiting body formation.

PMID- 15556031
TI  - Building filaments in the air: aerial morphogenesis in bacteria and fungi.
AB  - To disperse their spores to new sites, filamentous fungi and bacteria need to
      erect aerial filaments, which develop into fruiting bodies and spore-bearing
      structures. The first challenge to aerial development is breaking surface tension
      at an aqueous-air interface, and in both groups of microorganisms, surface-active
      proteins take part in the initiation of aerial morphogenesis. Comparative
      analysis of fungi and bacteria is providing new insights into the means by which
      aerial filamentation is accomplished.

PMID- 15556032
TI  - Biofilm formation in plant-microbe associations.
AB  - Bacteria adhere to environmental surfaces in multicellular assemblies described
      as biofilms. Plant-associated bacteria interact with host tissue surfaces during
      pathogenesis and symbiosis, and in commensal relationships. Observations of
      bacteria associated with plants increasingly reveal biofilm-type structures that
      vary from small clusters of cells to extensive biofilms. The surface properties
      of the plant tissue, nutrient and water availability, and the proclivities of the
      colonizing bacteria strongly influence the resulting biofilm structure. Recent
      studies highlight the importance of these structures in initiating and
      maintaining contact with the host by examining the extent to which biofilm
      formation is an intrinsic component of plant-microbe interactions.

PMID- 15556033
TI  - Biogenesis of the Gram-negative bacterial outer membrane.
AB  - Gram-negative bacteria are bounded by two membranes. The outer membrane consists
      of phospholipids, lipopolysaccharides, lipoproteins and integral outer membrane
      proteins, all of which are synthesized in the cytoplasm. Recently, much progress
      has been made in the elucidation of the mechanisms of transport of these
      molecules over the inner membrane, through the periplasm and into the outer
      membrane, in part by exploiting the extraordinary capacity of Neisseria
      meningitidis to survive without lipopolysaccharide.

PMID- 15556034
TI  - Integrative studies put cell wall synthesis on the yeast functional map.
AB  - The fungal cell wall field, traditionally focused on polysaccharide composition
      and synthesis, retains a certain static architectural imagery of structural
      rigidity and integrity, with the wall offering protection from a harsh
      environment. This picture of the wall is increasingly changing to that of a
      bustling construction site, as research uncovers the organizational complexity of
      its assembly. With recent molecular and genomic studies on Saccharomyces
      cerevisiae, cell wall synthesis and biology appear increasingly to be dynamic and
      adaptable processes that are fully integrated with the underlying cytoskeletal
      and polarity machinery that drive cell cycle progression.

PMID- 15556035
TI  - Sense and sensibility: nutritional response and signal integration in yeast.
AB  - Yeast cells respond to the quantity and quality of carbon and nitrogen sources in
      the environment both by adjusting their transcriptional and metabolic profiles to
      make optimum use of the available nutrients and by selecting a developmental
      program--budding, pseudohyphal differentiation, quiescence or sporulation--that
      maximizes their potential for survival under the existing nutrient conditions.
      Recent studies fueled by genomic tools have refined our knowledge of the
      components and connections within individual pathways and the interconnections
      between pathways. More significantly, these studies begin to paint an as yet
      inchoate portrait of the yeast cells' means of processing its environmental
      information, in which specific transcription factors and chromatin modifying
      activities coordinate input from several signaling pathways to yield an
      appropriate and coherent response of genes involved in mass accumulation and
      metabolism.

PMID- 15556036
TI  - Ribosome synthesis meets the cell cycle.
AB  - A large number of ribosome synthesis factors have been identified using proteomic
      analyses in yeast. The patterns of RNA and protein co-precipitation suggest that
      ribosome synthesis does not proceed via a linear progression of successive steps.
      Recent analyses have identified several interactions between factors clearly
      implicated in ribosome synthesis and specific steps in the cell division cycle.
      The intersections between these pathways were not anticipated, but potential
      explanations for their existence can be advanced.

PMID- 15556037
TI  - Transcriptional networks: reverse-engineering gene regulation on a global scale.
AB  - A major objective in post-genome research is to fully understand the
      transcriptional control of each gene and the targets of each transcription
      factor. In yeast, large-scale experimental and computational approaches have been
      applied to identify co-regulated genes, cis regulatory elements, and
      transcription factor DNA binding sites in vivo. Methods for modeling and
      predicting system behavior, and for reconciling discrepancies among data types,
      are being explored. The results indicate that a complete and comprehensive yeast
      transcriptional network will ultimately be achieved.

PMID- 15556038
TI  - Ubiquitin-dependent control of development in Saccharomyces cerevisiae.
AB  - In response to external environmental stimuli and intrinsic developmental cues,
      yeast cells reset their gene expression programs and change phenotype. These
      switches in cellular state require the dismantling of an initial regulatory
      program, in addition to the induction of different sets of genes to specify the
      new cell phenotype. Recent experiments examining the role of protein degradation
      in these transitions have highlighted the importance of inactivating previously
      utilized regulators and have led to advances in our understanding of how cells
      change from one phenotypic state to another.

PMID- 15556039
TI  - Apoptosis in yeast.
AB  - Apoptosis is a highly regulated cellular suicide program crucial for metazoan
      development. However, dysfunction of apoptosis also leads to several diseases.
      Yeast undergoes apoptosis after application of acetic acid, sugar- or salt
      stress, plant antifungal peptides, or hydrogen peroxide. Oxygen radicals seem to
      be key elements of apoptotic execution, conserved during evolution. Furthermore,
      several yeast orthologues of central metazoan apoptotic regulators have been
      identified, such as a caspase and a caspase-regulating serine protease. In
      addition, physiological occurrence of cell death has been detected during aging
      and mating in yeast. The finding of apoptosis in yeast, other fungi and parasites
      is not only of great medical relevance but will also help to understand some of
      the still unknown molecular mechanisms at the core of apoptotic execution.

PMID- 15556040
TI  - Through a glass opaquely: the biological significance of mating in Candida
      albicans.
AB  - Most Candida albicans strains are heterozygous at the MTL (mating-type-like)
      locus, but mating occurs in hemi- or homozygous strains. The white-opaque switch
      process is repressed by the heterodimer of the MTLa1 and MTLalpha2 gene products,
      while mating genes are induced by a2 and alpha1. Mating occurs in opaque cells
      and produces tetraploid progeny. A small percentage (3-7%) of clinical isolates
      are homozygous at the MTL locus and most are mating-competent. MTL gene
      expression is controlled in part by a gene which activates MTLalpha genes and
      represses MTLa genes in response to hemoglobin. A failure to find meiosis and the
      lack of evidence of mating in vivo, together with some of the properties of
      opaque cells, leads to the suggestion that mating may have persisted because the
      tightly associated switch facilitates the commensal lifestyle of this fungus.

PMID- 15556041
TI  - Regulation of mating and pathogenic development in Ustilago maydis.
AB  - The plant pathogenic fungus Ustilago maydis induces disease only in its
      dikaryotic stage that is generated after mating. This process involves
      coordinated cAMP and mitogen-activated protein kinase signalling to regulate
      transcriptional as well as morphological responses. Among the induced products is
      the key regulator for pathogenic development. Recent advances identified crucial
      nodes that interconnect these pathways. The key regulator orchestrates a complex
      transcriptional cascade, the components of which have been uncovered by genomic
      strategies. This is complemented by insights into organization, dynamics and
      function of the cytoskeleton, which begin to establish the links between
      signalling, intracellular transport processes and morphology.

PMID- 15556042
TI  - Aging and genetic instability in yeast.
AB  - There is a striking link between increasing age and the incidence of cancer in
      humans. One of the hallmarks of cancer, genomic instability, has been observed in
      all types of organisms. In the yeast Saccharomyces cerevisiae, it was recently
      discovered that during the replicative lifespan, aging cells switch to a state of
      high genomic instability that persists until they die. In considering these and
      other recent results, we suggest that accumulation of oxidatively damaged protein
      in aging cells results in the loss of function of gene products critical for
      maintaining genome integrity. Determining the identity of these proteins and how
      they become damaged represents a new challenge for understanding the relationship
      between age and genetic instability.

PMID- 15556043
TI  - Flexibility and governance in eukaryotic DNA replication.
AB  - Eukaryotic DNA replication begins at numerous but often poorly characterized
      sequences called origins, which are distributed fairly regularly along
      chromosomes. The elusive and idiosyncratic nature of origins in higher eukaryotes
      is now understood as resulting from a strong epigenetic influence on their
      specification, which provides flexibility in origin selection and allows for
      tailoring the dynamics of chromosome replication to the specific needs of cells.
      By contrast, the factors that assemble in trans to make these origins competent
      for replication and the kinases that trigger initiation are well conserved.
      Genome-wide and single-molecule approaches are being developed to elucidate the
      dynamics of chromosome replication. The notion that a well-coordinated
      progression of replication forks is crucial for many aspects of the chromosome
      cycle besides simply duplication begins to be appreciated.

PMID- 15556044
TI  - Heart failure--the importance of ethnicity.
AB  - Heart failure is a major public health problem in the Western world. Aetiological
      factors involved in its development include hypertension, diabetes, and ischaemic
      heart disease--all of which differ in prevalence, and possibly mechanism, between
      patients of differing ethnicity. Unfortunately, epidemiological and therapeutic
      trials have involved almost exclusively white populations, and evidence from
      these trials cannot necessarily be assumed to be generalisable to populations
      that include high proportions of patients from other ethnic origins. This review
      will discuss the mechanistic and therapeutic differences that exist in heart
      failure between those of European origin, and patients from the major ethnic
      minority groups of the UK.

PMID- 15556045
TI  - Regulation of caspase 3 and Fas in pressure overload-induced left ventricular
      dysfunction.
AB  - BACKGROUND: The presence of apoptotic cell death in cardiac myocytes is now well
      established and the contribution of apoptosis for the development of heart
      failure has been suggested. However, the mechanism responsible for the induction
      of apoptosis remains unclear. The present study was designed to investigate the
      involvement of Fas and caspase 3 in the transition from pressure overload-induced
      left ventricular hypertrophy (LVH) to left ventricular dysfunction (LVD).
      METHODS: Pressure overload induced LVH (10 days) and LVD (30 days) were induced
      by thoracic aortic banding. Changes in apoptosis-related genes were studied in
      rats with thoracic aortic banding. After 10 and 30 days, cardiac Fas mRNA
      expression was measured by RT-PCR. The mRNA expression of caspase 3 was detected
      by RNase protection assay. The activity of caspase 3 was measured by fluorometric
      assay. Protein levels of caspase 3 were measured by Western blot. RESULTS: Rats
      with aortic banding had increased heart/body weight ratios after 10 and 30 days,
      compared to controls. Central venous pressure and lung weights were increased,
      left ventricular contractility was significantly impaired only in rats after 30
      days of aortic banding, indicating LVD. Caspase 3 mRNA expression (7.1+/-0.1 vs.
      2.8+/-0.4, P<0.05), caspase 3 activity (1418+/-181 vs. 849+/-154 AU, P<0.05) as
      well as caspase 3 protein levels were increased in rats with LVD but not with
      LVH. Similarly, Fas mRNA was increased in rats with LVD. CONCLUSIONS: The
      activation of Fas and caspase 3 only after 30 days of aortic banding suggests
      that induction of these pathways may be involved in pressure overload-induced
      LVD.

PMID- 15556046
TI  - Erythropoietin improves left ventricular function and coronary flow in an
      experimental model of ischemia-reperfusion injury.
AB  - BACKGROUND: Recent studies show that erythropoietin (EPO) plays a protective role
      in brain ischemia. In this condition, administration of EPO protects neurons from
      ischemic damage. Recently, it has been shown that in patients with chronic heart
      failure (CHF), EPO treatment improved cardiac function. In the present study we
      assessed the role of EPO and EPO-receptor (EPO-R) in the heart. METHODS AND
      RESULTS: We studied the presence and functionality of the EPO-R in isolated rat
      hearts in the Langendorff set-up. Hearts were perfused for 20 min with 10 U/ml
      EPO or vehicle. Immunohistochemistry revealed the presence of the EPO-R on
      endothelial cells, fibroblasts and to a lesser extent cardiomyocytes.
      Furthermore, perfusion with EPO resulted in a 50% increase in the phosphorylated
      MAP kinases p42/p44. To evaluate the protective role of EPO in cardiac ischemia,
      we performed low-flow (0.6 ml/min) ischemia/reperfusion experiments in isolated
      rat hearts. Administration of EPO (10 U/ml) reduced the cellular damage by 56%
      (P<0.05) during reperfusion, diminished apoptosis by 15% (P<0.05) and resulted in
      a significantly improved recovery of left ventricular pressure (P=0.02) and
      coronary flow (P=0.01). CONCLUSION: The present data suggest that a functional
      EPO-R is present in rat adult cardiac tissue and that exogenous EPO
      administration improves cardiac function after ischemia/reperfusion injury.

PMID- 15556047
TI  - Two novel mutations in the beta-myosin heavy chain gene associated with dilated
      cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is familial in approximately 20-35% of
      cases of idiopathic DCM. Several mutations in the different sarcomere protein
      genes have been reported to cause DCM. AIMS: We wanted to investigate the role of
      sarcomere protein gene variants in Finnish DCM patients. METHODS AND RESULTS: We
      screened all coding exons of five sarcomere protein genes (beta-myosin heavy
      chain, alpha-tropomyosin, troponin C, troponin I and troponin T) in a well
      characterized population of 52 DCM patients in Eastern Finland by the PCR-SSCP
      and sequencing method. Two novel mutations, Arg1053Gln and Arg1500Trp, in the
      beta-myosin heavy chain gene in two index patients were detected. The proband
      with the Arg1053Gln mutation had a dilated left ventricle and impaired systolic
      function, but other family members carrying this mutation presented with septal
      hypertrophy. It thus seems that the Arg1053Gln mutation is primarily a HCM
      mutation, which can also lead to DCM. The other mutation, Arg1500Trp, was
      associated with a typical DCM phenotype. The Arg1500Trp mutation carrier had only
      one family member alive, but she did not carry the mutation and, therefore,
      cosegregation of the mutation and the disease in this family could not be
      reliably verified. No disease-causing mutations were found in the other sarcomere
      protein genes. CONCLUSIONS: Two novel mutations in the beta-myosin heavy chain
      gene were detected in patients with DCM. Overall, mutations in the beta-myosin
      heavy chain gene seem to be relatively uncommon in Finnish DCM patients.

PMID- 15556048
TI  - Increased expression of tumor necrosis factor-alpha converting enzyme and tumor
      necrosis factor-alpha in peripheral blood mononuclear cells in patients with
      advanced congestive heart failure.
AB  - BACKGROUND: Tumor necrosis factor-alpha converting enzyme (TACE) has recently
      been identified as a metalloproteinase-disintegrin, which converts pro-tumor
      necrosis factor-alpha (TNF-alpha) to the mature form, and is an important
      mediator in the pathogenesis of CHF. AIMS: In order to establish the importance
      of TACE in the regulation of TNF-alpha synthesis in peripheral blood mononuclear
      cells (PBMC), we analyzed mRNAs and protein-positive cells of both TACE and TNF
      alpha in PBMC obtained from patients with congestive heart failure (CHF). METHODS
      AND RESULTS: PBMC were obtained from 46 patients with CHF and 22 controls. PBMC
      were activated by phorbol 12-myristate 13-acetate and ionomycin and assessed for
      TACE and TNF-alpha mRNAs by real-time RT-PCR, intracellular TACE and TNF-alpha
      levels by flow cytometry, and TNF-alpha secretion by supernatant ELISA. Levels of
      TACE and TNF-alpha mRNAs, intracellular TACE and TNF-alpha, and supernatant TNF
      alpha were higher in CHF than in controls (P<0.001). There was a positive
      correlation between TACE and TNF-alpha levels in CHF patients (mRNA: r=0.60,
      P<0.001, intracellular protein levels: r=0.76, P<0.001). When the CHF group was
      divided into two subgroups by NYHA functional class (I and II vs. III and IV),
      levels of TACE and TNF-alpha were significantly higher in severe CHF patients
      (NYHA III or IV) than in mild CHF patients (NYHA I or II) (mRNA: P<0.001;
      intracellular protein levels: P<0.001). CONCLUSION: These results demonstrate
      that in patients with CHF, and especially those with severe CHF, TACE expression
      in PBMC increases with TNF-alpha expression. These observations suggest that TACE
      in PBMC is an important regulator of TNF-alpha maturation, meaning that TACE may
      be a potential target for the inhibition of cellular TNF-alpha production in CHF.

PMID- 15556049
TI  - Soluble TNF-alpha and interleukin-6 receptors in the urine of heart failure
      patients. Their clinical value and relationship with plasma levels.
AB  - BACKGROUND: Proinflammatory cytokines are important mediators in heart failure
      (HF). Recently, urinary levels of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) have been determined. AIMS: The purpose of this study was to
      measure the urinary levels of TNF-alpha and IL-6 receptors, sTNF-RI, sTNF-RII,
      sIL-6R, and the relationship with plasma levels and NYHA classes in HF. METHODS:
      Plasma and urine were collected from 114 HF patients and sTNF-RI, sTNF-RII and
      sIL-6R (ng/ml) were analyzed. RESULTS: For the whole population, plasma levels of
      sTNF-RI were 2.1+/-0.1, of sTNF-RII were 5.0+/-0.3 and of sIL-6R were 49.8+/-2.5.
      Urinary levels were: sTNF-RI, 2.8+/-0.5, r=0.5, p<0.001; sTNF-RII, 12.6+/-2.1,
      r=0.4, p<0.001; and sIL-6R, 4.2+/-0.4, NS. In NYHA III subjects, we found sTNF
      RI, r=0.6, p<0.01, sTNF-RII, r=0.5, p<0.05, and sILR-6, r=0.5, p<0.05. Both
      plasma TNF receptors and urinary levels of sTNF-RII were higher in patients in a
      more severe NYHA class (p<0.05). CONCLUSIONS: Urine is a good environment to
      study sTNF-RI and sTNF-RII, and this fact has diagnostic and prognostic
      implications. Plasma and urinary levels of TNF receptors showed a fair
      correlation, which was increased in higher NYHA classes. Plasma and urinary
      levels of sIL6R showed a good correlation in NYHA III. The TNF receptor levels in
      urine increased in patients with more severe HF.

PMID- 15556050
TI  - Elevated circulating levels of thioredoxin and stress in chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is a complex syndrome, in which reactive
      oxygen species and inflammatory cytokines are important stressors that contribute
      to the pathogenesis. AIM: We have studied physiological stress response
      parameters in CHF, in particular the redox-active regulator thioredoxin.
      SUBJECTS: A case-control study was conducted including a consecutive sample of
      CHF patients (n=27) of NYHA class II and III; comparison control subjects (n=29)
      were recruited from an association for retired people. METHOD: Baseline levels of
      Trx, lipid peroxides (oxidative stress), TNF and IL-6 cytokines, platelet
      activation marker P-selectin, cortisol (as peripheral effector of HPA axis), and
      the potent antioxidant selenoprotein Trx-reductase were assessed. RESULTS: Mean
      (+/-S.E.M.) plasma levels of Trx were significantly higher in patients with CHF
      (32+/-3 ng/ml), than in the healthy subjects (12+/-3 ng/ml, P<0.0001). Trx levels
      increased in proportion to severity of disease (NYHA class III>NYHA class II) and
      degree of stress. Trx elevation correlated well with increased oxidative stress
      (lipid peroxides, P<0.0001), circulatory P-selectin (P<0.0001), morning level of
      free salivary cortisol (P=0.0002), and serum creatinine (P=0.0417), but not with
      pro-inflammatory cytokines TNF and IL-6. CONCLUSION: Trx was strikingly elevated
      in heart failure cases compared with controls, signifying an adaptive stress
      response that is higher the more severe the disease.

PMID- 15556051
TI  - Is plasma N-BNP a good indicator of the functional reserve of failing hearts? The
      FRESH-BNP study.
AB  - AIMS: Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in
      the diagnosis of heart failure (HF) depends traditionally on whether it is as
      good as the putative 'gold-standard', left ventricular ejection fraction (LVEF),
      in indicating cardiac dysfunction. However, since HF is primarily an impairment
      of function of the cardiac pump, we explored the relationship between N-BNP and
      direct and indirect indicators of cardiac pump dysfunction. METHODS AND RESULTS:
      Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/
      15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the
      study and had resting N-BNP measured. Cardiopulmonary exercise testing was
      performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects
      underwent further exercise haemodynamic assessment to evaluate peak cardiac power
      output (CPO). The CHF group had significantly higher N-BNP (median [interquartile
      range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml,
      P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and
      peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation
      was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between
      LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant.
      Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as
      independent predictors of peak Vo(2). CONCLUSIONS: We have found that N-BNP was
      surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart
      failure is an inadequacy of function, these results strongly support the notion
      that N-BNP is a useful blood test in estimating the extent of cardiac pump
      dysfunction and helpful in establishing positive diagnosis of heart failure.

PMID- 15556052
TI  - Impaired endothelium-dependent and -independent vasodilation in elderly patients
      with chronic heart failure.
AB  - BACKGROUND: Impaired endothelium-dependent and independent vasodilator responses
      in chronic heart failure (CHF) have been well described. Previous studies
      involved younger patients and omitted medications prior to study. AIMS: We
      explored if new therapeutic interventions would restore vasodilator responses in
      typical patients with chronic heart failure. METHODS AND RESULTS: 24 patients and
      15 controls were recruited, patients were maintained on their usual medications.
      Forearm blood flow responses were measured by venous occlusion plethysmography in
      response to incremental doses of sodium nitroprusside (SNP) (6, 9 and 12
      nmol/min), acetylcholine (ACH) (120, 180 and 240 nmol/min), angiotensin II (AII)
      (1, 10 and 100 nmol/min) and N(g)-Nitro-L-arginine methyl ester (L-NAME) (1, 2
      and 4 nmol/min) infused into the non-dominant brachial artery. FBF responses to
      SNP were impaired in patients compared with controls (13.7(9.9,17.4) vs.
      24.8(18.6,30.9)) arbitrary units, P<0.001). Similarly FBF responses to ACH were
      reduced in patients compared with controls (7.5(4.2,10.9) vs. 24.8(16.4,33.2))
      arbitrary units, P<0.001. Decreased FBF was noted in response to AII and L-NAME
      but was significant only for AII and did not differ between groups. CONCLUSIONS:
      In elderly patients with CHF, endothelium-dependent and independent vasodilator
      responses were blunted compared with controls. Defects in nitric oxide
      bioavailability and smooth muscle responsiveness are not reversed by modern
      medical management of the heart failure syndrome.

PMID- 15556053
TI  - Acute administration of diclofenac, but possibly not long term low dose aspirin,
      causes detrimental renal effects in heart failure patients treated with ACE
      inhibitors.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) or high doses of
      aspirin (acetylsalicylic acid) can exert detrimental effects on renal function
      and counteract the beneficial effects of angiotensin-converting enzyme (ACE)
      inhibitors in patients with congestive heart failure. AIMS: The objective of our
      study was to evaluate the renal effects of low dose aspirin and the NSAID
      diclofenac in patients with congestive heart failure treated with ACE-inhibitors.
      METHODS: Ten patients on their individually titrated dose of ACE-inhibitors and
      low dose aspirin (< or =125 mg daily) with stable congestive heart failure from
      coronary artery disease, entered an open investigation while on low dose aspirin,
      which was then discontinued. After one week wash-out they received an oral dose
      of 50 mg diclofenac potassium or placebo in a double-blind cross-over fashion
      with a one week wash-out period between treatments. RESULTS: Diclofenac caused
      significant (P<0.05) decreases in GFR, urine flow, osmolality clearance, and
      excretion rates of sodium and potassium compared to placebo and aspirin. At
      t(max) for diclofenac or corresponding time for placebo diclofenac caused 40 (11
      59)% (geometric mean and 95% confidence limits) reduction in GFR compared to
      placebo and 36 (5.4-56)% reduction to low-dose aspirin. No significant changes
      between low dose aspirin and placebo were found. CONCLUSION: Acute administration
      of diclofenac, but not long term low dose aspirin, has profound impact on renal
      function in patients with heart failure treated with ACE-inhibitors and may cause
      worsened heart failure.

PMID- 15556054
TI  - Biomechanical efficiency is decreased in heart failure during low-level steady
      state and maximal ramp exercise.
AB  - BACKGROUND: Previous studies of biomechanical efficiency (external work/energy
      input--Watt/O(2) consumed) in heart failure (HF) using cardiopulmonary exercise
      testing (CPET) and magnetic resonance spectroscopy (MRS) have had discordant
      results with increased efficiency by CPET and decreased efficiency by MRS. AIMS:
      Compare biomechanical efficiency of HF subjects and normal controls during steady
      state (SS=35 W for 6 min) and ramp cycle ergometer exercise. The hypothesis was
      that HF subjects would have impaired biomechanical efficiency that correlated
      with HF symptoms. METHODS: Biomechanical efficiency used the actual Vo(2) during
      exercise and recovery. Gross (Vo(2) above zero), Net (Vo(2) above the resting
      Vo(2)) and Work (Vo(2) above the unloaded pedaling Vo(2)) efficiencies were
      calculated. RESULTS: HF subjects had an 18% higher Vo(2) during SS exercise
      (P=0.029). Biomechanical efficiency was reduced during SS exercise (gross -15%,
      P=0.019, net -15%, P=0.062, and work -35%, P=0.002). Gross Efficiency during SS
      exercise had the strongest correlation with HF symptoms (r=0.55). During ramp
      exercise gross (-26%), net (-10%) and work (-8%) biomechanical efficiency were
      all reduced (all P<0.05). The slope of the Vo(2)/Watt relationship during ramp
      exercise had the best correlation with HF symptoms (r=0.46). CONCLUSIONS: HF
      subjects have an increased O(2) cost/Watt during SS and ramp exercise that
      correlates with HF symptoms of fatigue and breathlessness. Methods to improve
      biomechanical efficiency in HF subjects by exercise training or medications may
      improve the symptoms and the impaired exercise capacity associated with HF.

PMID- 15556055
TI  - A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on
      functional capacity in patients with symptomatic left ventricular systolic
      dysfunction.
AB  - AIM: To determine by meta-analysis whether angiotensin-converting enzyme (ACE)
      inhibitors improve exercise tolerance in patients with symptomatic left
      ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: After literature
      search 13 multi-centre double blind parallel group trials that evaluated the
      effect of ACE inhibitors vs. placebo on exercise duration were selected. Ninety
      four percent of patients were in New York Heart Association class II-IV. The
      studies were combined using the Cochrane meta-analysis program (Review manager
      version 4.1). Analyses according to treatment period, exercise protocols and
      publication periods were performed. Treatment with ACE inhibitor over 4-12 weeks
      resulted in a beneficial effect on exercise duration (P=0.003 and P=0.0008 for 4-
      and 12-weeks treatment, respectively), but the magnitude of improvements did not
      exceed 30 s corresponding to only 5% compared with placebo. CONCLUSION: In
      addition to the pronounced effect on mortality and morbidity in patients with
      symptomatic LVSD, ACE inhibitors have improving effect on functional capacity
      measured as exercise tolerance time.

PMID- 15556056
TI  - Effect of valsartan added to background ACE inhibitor therapy in patients with
      heart failure: results from Val-HeFT.
AB  - AIMS: To investigate the effect of valsartan in the Valsartan-Heart Failure Trial
      (Val-HeFT) when added to angiotensin-converting enzyme inhibitor (ACEi) alone in
      patients with heart failure (HF). METHODS: Subjects in Val-HeFT receiving ACEi
      but not beta-blocker at baseline were analysed; 1532 were assigned to valsartan
      and 1502 assigned to placebo. Primary outcome events (all-cause mortality,
      hospitalisation for adjudicated heart failure, sudden death with resuscitation
      and need for >4 h of parenteral therapy for worsening heart failure) were
      monitored. RESULTS: Mortality was not affected by valsartan but morbidity
      endpoints were significantly reduced (36.3% in placebo, 31.0% in valsartan,
      p=0.002) in patients receiving an ACEi but no beta-blocker. Quality of life (QOL)
      was significantly improved, ejection fraction (EF) significantly increased, left
      ventricular (LV) diameter significantly reduced and plasma B-type natriuretic
      peptide, norepinephrine and aldosterone levels significantly reduced with
      valsartan compared to placebo. The morbidity benefit was significant in patients
      on ACEi doses below the median (22% reduction, p=0.003) and not statistically
      significant in those receiving ACEi doses above the median (14% reduction,
      p=0.143). CONCLUSION: Valsartan reduces heart failure hospitalisations and slows
      LV remodelling in patients treated with an ACEi in the absence of beta-blockade,
      particularly in those on lower doses of ACEi.

PMID- 15556057
TI  - Austrian survey of treating heart failure--AUSTRIA.
AB  - BACKGROUND: Treatment of chronic heart failure is based on the results of large
      clinical trials, which form the basis of treatment guidelines, such as those from
      the European Society of Cardiology (ESC). The aim of this study was to record
      treatment-modalities and the implementation of guidelines of chronic heart
      failure in clinical practice in Austria. METHODS: Overall 96 general physicians,
      specialists for internal medicine in private practice or in hospital outpatient
      departments participated in the survey. Physicians were asked to prospectively
      document 30 consecutive patients with chronic heart failure. RESULTS: 1880
      patients were documented. The majority of patients were treated by general
      physicians (57%). Coronary artery disease was the most frequent aetiology for
      heart failure (47%). The most frequently used drugs were blockers of the renin
      angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor
      blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like
      digitalis and spironolactone were used infrequently. Average doses of ACE
      inhibitors were approximately 90% of those recommended by the ESC, average doses
      of beta-blockers were approximately 50% of those recommended. Treatment among the
      three classes of physicians differed with respect to RAS-blockers and beta
      blockers, which were used infrequently by general practitioners. Both groups of
      drugs were given more frequently to younger patients (<70 years) while digitalis
      was given more often to elderly patients. CONCLUSIONS: Results from this survey
      suggest that Austrian physicians treating patients with heart failure use the
      appropriate drugs in dosages that are suggested by recently published guidelines
      (ACE-inhibitors and beta-blockers). However, dosages of spironolactone clearly
      differed from current recommendations.

PMID- 15556058
TI  - Clinical trials update from the Heart Failure Society of America: EMOTE, HERB
      CHF, BEST genetic sub-study and RHYTHM-ICD.
AB  - This article summarises key presentations relevant to the pathophysiology,
      prevention or treatment of heart failure, from the Heart Failure Society of
      America annual meeting held in Toronto, Canada. Data from the EnoxiMone in
      intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3
      inhibitor enoximone may be effective for weaning severe heart failure patients
      from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in
      CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional
      heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of
      Survival Trial (BEST) study showed that bucindolol reduced mortality and
      hospitalisations in patients who were homozygous for the Arg389 variant of the
      beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart
      Failure Management (RHYTHM-ICD) study, patients randomised to cardiac
      resynchronisation therapy (CRT) showed an improvement in symptoms and functional
      capacity compared to the control group.

PMID- 15556059
TI  - Estrogenic octylphenol affects seminal fluid production and its biochemical
      composition of eelpout (Zoarces viviparus).
AB  - Estrogenic chemicals such as alkylphenols (APs) have been shown to disrupt the
      reproductive system of male fish. In the present study, the effects of the
      estrogenic chemical octylphenol (100 microg g(-1)) and 17 beta-estradiol on the
      semen production and the biochemical composition of the seminal fluid of the
      viviparous eelpout (Zoarces viviparus) were investigated at the time of spawning.
      After 10 days of octylphenol or estrogen treatment, vitellogenin (Vtg) synthesis
      was induced as indicated by increased plasma vitellogenin concentration. In
      accordance with the increased vitellogenin concentration, hepatosomatic index
      (HSI), total protein concentration, and total calcium concentration were also
      increased, and free amino acids concentration was decreased in blood plasma.
      Octylphenol treatment caused a decrease in the gonadosomatic index (GSI) and the
      milt volume and an increase in the spermatocrit. The histological examination
      revealed that octylphenol affected the normal lobular structure, including the
      Sertoli cells. In the majority of the octylphenol-treated fish, trapped sperm
      cells were observed in parts of the seminiferous lobules and the sperm ducts. The
      biochemical composition of the seminal fluid was also affected by the octylphenol
      or estrogen. The seminal plasma concentrations of magnesium, calcium, and total
      protein were elevated, and the concentration of free amino acids was reduced in
      the treated fish. This study indicates that octylphenol inhibits the seminal
      fluid production and changes its biochemical composition in eelpouts.

PMID- 15556060
TI  - Reproductive aspects in female rats exposed prenatally to hydrocortisone.
AB  - We investigated the effects of hydrocortisone during the prenatal period and its
      later repercussion on reproductive aspects of female rats. Pregnant rats were
      treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and
      19th days of pregnancy. Although the present study was not intended to identify
      mechanisms of toxicity, the treatment with hydrocortisone in the last period of
      pregnancy presented no signs of toxicity. The efficacy of the hydrocortisone in
      reducing the adrenal wet mass and plasma corticosterone levels immediately after
      delivery in both the treated mothers and in respective pups at birth may indicate
      impairment of the hypothalamus-pituitary-adrenal axis. In addition, the treatment
      with hydrocortisone did not interfere in the development of the female
      descendants until puberty. However, it affected the estrous cycle and fertility.
      Probably, the prenatal exposure to corticosteroids had altered at least partially
      the hypothalamus-pituitary-gonadal axis, resulting in the damages observed in
      adult life. These results indicate that the use of the hydrocortisone at a dose
      that apparently does not endanger the neonate led to undesirable effects in the
      adult reproductive phase, resulting in later deleterious alteration of the
      reproductive physiology in female rats.

PMID- 15556061
TI  - In vitro effects of wastewater treatment plant effluent on sea bass red blood
      cells.
AB  - Red blood cells of marine fish have been used in suitable biological assays to
      study the (eco)toxicity of wastewater treatment plant effluents. The aim of the
      present work was to draw upon their more relevant effects on cell hemolysis, ATP
      content, osmotic resistance and cell volume regulation. Following physico
      chemical treatment, treatment plant effluents showed a residual toxicity
      resulting from multiple impairment of cell metabolism and structures. The
      earliest and most sensitive effects were related to the regulation of
      intracellular osmotic pressure leading to decreased cell water volume. Such
      effects were also observed following short-term incubation in 10-fold diluted
      effluent. Other damages were found following incubation in non-diluted effluent.
      Membrane structure was affected leading to increased osmotic resistance. Later, a
      decrease of the intracellular ATP level was found, followed by hemolysis. The
      presence of glucose in the incubation medium lessened the fall in ATP content and
      hemolysis in the treated cells but also in control cells.

PMID- 15556062
TI  - Prior PCB exposure suppresses hypoxia-induced up-regulation of glycolytic enzymes
      in Fundulus heteroclitus.
AB  - Increased activity of the glycolytic enzymes is a conserved feature of the
      cellular response to hypoxia, and may represent a protective mechanism by which
      cells can survive short-term hypoxic exposure. Gene induction by hypoxia involves
      a dimer of the hypoxia inducible factor (HIF)-1 alpha and the nuclear cofactor
      HIF-1 beta, also called the aryl hydrocarbon receptor nuclear translocator
      (ARNT), which is also involved in induction of genes in response to aryl
      hydrocarbon exposure. To assess the possibility of interaction between these
      pathways, we examined changes in the activity of the glycolytic enzymes in
      response to hypoxia and polychlorinated biphenyl (PCB) exposure in the liver of a
      teleost fish, Fundulus heteroclitus. After 3 days of hypoxic exposure (dissolved
      oxygen levels between 1.5 and 2.0 mg/L), there were significant increases in the
      activity of six glycolytic enzymes (PGI, ALD, TPI, PGK, PGM and LDH). In
      contrast, intraperitoneal injection of 1 microg/g body weight of PCB #77
      (3,3',4,4'-tetrachlorobiphenyl) caused significant decreases in glycolytic enzyme
      activity after 7 days of exposure. When fish were injected with PCB #77 and then
      (4 days later) exposed to hypoxia for 3 days as before, we observed no induction
      of the glycolytic enzymes. This suggests that there is an antagonistic
      interaction between exposure to PCBs and hypoxia in F. heteroclitus. Prior PCB
      exposure could make these fish less tolerant of environmental hypoxia.

PMID- 15556063
TI  - Purification and characterization of antimicrobial peptides from the skin
      secretions of the mink frog (Rana septentrionalis).
AB  - Skin secretions were obtained from male, female, and juvenile specimens of the
      mink frog (Rana septentrionalis) by electric stimulation and shown to contain 10
      peptides that differentially inhibited the growth of microorganisms. The elution
      profiles of secretions from the three groups following reverse-phase HPLC were
      almost identical indicating that there were no major sexual or developmental
      differences in chemical composition. Four peptides of the brevinin-1 family, with
      potent antimicrobial activity and strong hemolytic activity, two members of
      ranatuerin-2 family and three members of the temporin family, were purified and
      characterized structurally. A 21-amino-acid C-terminally alpha-amidated peptide
      (GIWDTIKSMGKVFAGKILQNL.NH(2)) with broad-spectrum antimicrobial activity was also
      isolated from the skin secretions. This peptide shows limited structural
      similarity with the N-terminal region of brevinin-2 peptides previously isolated
      from R. temporaria skin but lacks the C-terminal cyclic heptapeptide domain
      associated with this family. Molecular and morphological data support the
      placement of R. septentrionalis in the R. catesbeiana species group, but analysis
      based upon the distribution of the molecular forms of the antimicrobial peptides
      is indicative of a closer phylogenetic relationship between R. septentrionalis
      and the frogs of the R. pipiens and R. boylii groups.

PMID- 15556064
TI  - Phase I and II liver enzyme activities in juvenile alligators (Alligator
      mississippiensis) collected from three sites in the Kissimmee-Everglades
      drainage, Florida (USA).
AB  - We examined CYP1A (measured using hepatic EROD and MROD activities) and
      glutathione-S-transferase (GST) activities in juvenile alligators (Alligator
      mississippiensis) collected from three sites with varying contamination in the
      Kissimmee-Everglades drainage in south Florida. We hypothesized that contaminants
      present in areas with intermediate or higher contaminant concentrations would
      alter hepatic enzyme activities in juvenile alligators from those sites when
      compared to hepatic enzyme activity in animals from the area with the least
      contamination. EROD activity was found to be higher in animals from the site with
      lower reported levels of contamination relative to those from the site with the
      highest reported contamination suggesting an inhibition of CYP1A expression or
      activity. No differences among animals from the three sites were observed for
      hepatic MROD and GST activities. A significant negative relationship between
      EROD, MROD, and GST activities and body size was exhibited in alligators from the
      site with the lowest contamination. No relationship between body size and hepatic
      enzyme activity was found in animals from the sites with intermediate and higher
      contamination, suggesting that contaminants present at these sites act to alter
      this relationship. No correlation was observed in this study between plasma
      steroid concentrations (estradiol-17 beta or testosterone) and hepatic EROD,
      MROD, or GST activities.

PMID- 15556065
TI  - Life-stage-dependent sensitivity of zebrafish (Danio rerio) to estrogen exposure.
AB  - The aim of this study was to identify periods in zebrafish (Danio rerio)
      development when estrogen exposure has long-term consequences on reproductive
      capabilities at the adult stage. To this end, zebrafish were exposed to 10 ng/L
      ethynylestradiol (EE(2)) during three stages of gonadal differentiation: (i) the
      juvenile hermaphroditic stage when gonads display the morphology of an immature
      ovary (in our zebrafish colony this lasted from 15 to 42 days post-fertilization
      [dpf]), (ii) the gonad transition stage when the hermaphroditic gonad
      differentiates into either testes or ovary (from 43 to day 71 dpf), and (iii) the
      premature stage of testicular and ovarian development (from 72 to 99 dpf). The
      consequences of stage-specific exposure to EE(2) were assessed by determining
      time to first spawning, fecundity (number of eggs per female per day),
      fertilization success (percentage of fertilized eggs) and sex ratio of the
      adults. Exposure during the gonad transition period induced a delay in the onset
      of spawning and a significant reduction of fecundity and fertilization success,
      whereas exposure during the hermaphroditic stage or during the premature stage
      had no significant impact on the reproductive parameters of adult fish. The
      results from this experiment pointed to the gonad transition stage as being most
      susceptible to persistent effects of developmental estrogen exposure. In a second
      experiment, the concentration dependency of the EE(2)effects was evaluated by
      exposing zebrafish during the gonad transition stage (43-71 dpf) to 1.67, 3 or 10
      ng EE(2)/L. Significant effects of EE(2) on adult reproduction were found with 3
      and 10 ng EE(2)/L, but not with 1.67 ng/L. Histological examination of the gonads
      revealed that at termination of EE(2) exposure (71 dpf), all individuals in the 3
      and 10 ng EE(2)/L treatment possessed ovaries. However, this feminising effect
      appeared to be reversible since at the adult stage (190 dpf), both fish with
      ovaries and with testes were found. Thus, EE(2) exposure during the gonad
      transition stage seems to have no persistent effect on gonad histology but on
      reproductive capabilities.

PMID- 15556066
TI  - Effects of prolactin and growth hormone on plasma levels of lysozyme and
      ceruloplasmin in rainbow trout.
AB  - In vivo and in vitro effects of prolactin (PRL) and growth hormone (GH) on plasma
      levels of lysozyme and ceruloplasmin were examined in the rainbow trout
      (Oncorhynchus mykiss). Hypophysectomy had no effect on the plasma lysozyme level.
      Implantation of PRL- or GH-containing cholesterol pellets increased the lysozyme
      level in a dose-related manner. After hypophysectomy and sham operation, plasma
      ceruloplasmin was elevated above the level in intact fish, suggesting
      inflammation caused by the surgery. PRL or GH treatment significantly attenuated
      the increased level of ceruloplasmin in the operated fish. Expression of lysozyme
      mRNA was detected in the leucocytes isolated from the peripheral blood by RT-PCR.
      In vitro administration of PRL or GH showed no effect on the proliferation of
      isolated leucocytes or on the total protein content; however, lysozyme activity
      in the medium increased in a dose-related manner. These results suggest that PRL
      and GH directly stimulate lysozyme production without affecting the proliferation
      of leucocytes, and the attenuated ceruloplasmin level increased in response to
      inflammation.

PMID- 15556067
TI  - IGF-binding proteins mediate TGF-beta 1-induced apoptosis in bovine mammary
      epithelial BME-UV1 cells.
AB  - TGF-beta 1 is an antiproliferative and apoptogenic factor for mammary epithelial
      cells (MEC) acting in an auto/paracrine manner and thus considered an important
      local regulator of mammary tissue involution. However, the apoptogenic signaling
      pathway induced by this cytokine in bovine MEC remains obscure. The present study
      was focused on identification of molecules involved in apoptogenic signaling of
      transforming growth factor-beta 1 (TGF-beta 1) in the model of bovine mammary
      epithelial cell line (BME-UV1). Laser scanning cytometry (LSC), Western blot and
      electrophoretic mobility shift assay (EMSA) were used for analysis of expression
      and activity of TGF-beta 1-related signaling molecules. The earliest response
      occurring within 1-2 h after TGF-beta 1 administration was an induction and
      activation of R-Smads (Smad2 and Smad3) and Co-Smad (Smad4). An evident formation
      of Smad-DNA complexes began from 2nd hour after MEC exposure to TGF-beta 1.
      Similarly to Smads, proteins of AP1 complex: phosphorylated c-Jun and JunD
      appeared to be early reactive molecules; however, an increase in their expression
      was detected only in cytosolic fraction. In the next step, an increase of IGF
      binding protein-3 (IGFBP-3) and IGFBP-4 expression was observed from 6th hour
      followed by a decrease in the activity of protein kinase B (PKB/Akt), which
      occurred after 24 h of MEC exposure to TGF-beta 1. The decrease in PKB/Akt
      activity coincided in time with the decline of phosphorylated Bad expression
      (inactive form). Present study supported additional evidence that stimulation of
      insulin-like growth factor I (IGF-I) was associated with complete abrogation of
      TGF-beta 1-induced activation of Bad and Bax and in the consequence protection
      against apoptosis. In conclusion, apoptotic effect of TGF-beta 1 in bovine MEC is
      mediated by IGFBPs and occurs through IGF-I sequestration, resulting in
      inhibition of PKB/Akt-dependent survival pathway.

PMID- 15556068
TI  - Stimulation of growth hormone secretion from seabream pituitary cells in primary
      culture by growth hormone secretagogues is independent of growth hormone
      transcription.
AB  - The action of a number of growth hormone secretagogues (GHS) on growth hormone
      (GH) secretion and gene expression was studied in a primary culture of pituitary
      cells isolated from the black seabream Acanthopagrus schlegeli. The peptide GHS
      employed included growth hormone-releasing peptide (GHRP)-2, ipamorelin, and
      human ghrelin. The nonpeptide GHS employed included the benzolactam GHS L692,585
      and the spiropiperidine GHS L163,540. Secreted GH was measured in the culture
      medium by an enzyme-linked immunosorbent assay (ELISA) method using a specific
      antibody against seabream GH. The GH mRNA content in the incubated cells was
      assessed by reverse transcription polymerase chain reaction (RT-PCR) using a pair
      of gene-specific primers designed from the cloned black seabream GH cDNA
      sequence. A dose-dependent stimulation of GH release was demonstrated by all the
      GHS tested, except human ghrelin, with EC(50) values in the nanomolar range.
      Simultaneous measurement of GH mRNA levels in the incubated seabream pituitary
      cells indicated that the GHS-stimulated increase in GH secretion was not
      paralleled by corresponding changes in GH gene expression. In contrast to the
      situation previously reported in the rat, no change in GH gene expression was
      noticed in the seabream pituitary cells even though the time of stimulation by
      GHS was increased up to 48 h, confirming that the GHS-stimulated GH secretion in
      seabream is independent of GH gene transcription.

PMID- 15556069
TI  - Glutathione S-transferase in the developmental stages of the insect Apis
      mellifera macedonica.
AB  - We investigated the pattern of glutathione S-transferase (GST) activity in the
      course of the development of Apis mellifera macedonica. GST activity is present
      in all developmental stages of A. mellifera macedonica. The highest activity
      towards the substrate 1-chloro-2,4-dinitrobenzene (CDNB) is found in the adult
      stage and the lowest in the egg. The kinetic characteristics of the whole enzyme
      change as the insect develops. Significant changes are observed in substrate
      specificity, inhibitor sensitivity and V(max). The number of isoenzymes and their
      rate of expression vary as the insect develops. However, two main isoenzymes are
      present in all developmental stages, one in the alkaline area and the other in
      the acidic. While in the larval stage the acidic isoenzyme is expressed at a
      slightly higher rate (52.2% over 47.8% for the alkaline isoenzyme), in the adult
      stage, the rate is reversed dramatically (13.24% and 84.2%, respectively).

PMID- 15556070
TI  - Glutathione S-transferase in the insect Apis mellifera macedonica kinetic
      characteristics and effect of stress on the expression of GST isoenzymes in the
      adult worker bee.
AB  - The glutathione S-transferase present in the adult worker bee Apis mellifera
      macedonica was purified and analyzed for its physicochemical and kinetic
      properties. The enzyme is heterodimeric with subunit molecular masses of 29 and
      25 kDa, respectively. Two main isoenzymes with distinct kinetic properties are
      present, with isoelectric points of 7.40 for the alkaline and 4.58 for the acidic
      forms, respectively. The two enzymes are induced independently by factors such as
      insecticide treatments and environmental conditions, including low temperatures
      or starvation.

PMID- 15556071
TI  - Plasma appearance of unesterified astaxanthin geometrical E/Z and optical R/S
      isomers in men given single doses of a mixture of optical 3 and 3'R/S isomers of
      astaxanthin fatty acyl diesters.
AB  - Appearance, pharmacokinetics and distribution of astaxanthin all-E-, 9Z- and 13Z
      geometrical and (3R,3'R)-, (3R,3'S)- and (3S,3'S)-optical isomers in plasma
      fractions were studied in three middle-aged male volunteers (41-50 years) after
      ingestion of a single meal containing first a 10-mg dose equivalent of
      astaxanthin from astaxanthin diesters, followed by a dose of 100 mg astaxanthin
      equivalents after 4 weeks. Direct resolution of geometrical isomers and optical
      isomers of astaxanthin dicamphanates by HPLC after saponification showed that the
      astaxanthin consisted of 95.2% all-E-, 1.2% 9Z- and 3.6% 13Z-astaxanthin, of
      (3R,3'R)-, (3R,3'S; meso)- and (3S,3'S)-astaxanthin in a 31:49:20 ratio. The
      plasma astaxanthin concentration-time curves were measured during 76 h.
      Astaxanthin esters were not detected in plasma. Maximum levels of astaxanthin
      (C(max)=0.28+/-0.1 mg/l) were reached 11.5 h after administration and the plasma
      astaxanthin elimination half-life was 52+/-40 h. The C(max) at the low dose was
      0.08 mg/l and showed that, the dose response was non-linear. The (3R,3'R)
      astaxanthin optical isomer accumulated selectively in plasma compared to the
      (3R,3'S)- and (3S,3'S)-isomers, and comprised 54% of total astaxanthin in the
      blood and only 31% of total astaxanthin in the administered dose. The astaxanthin
      Z-isomers were absorbed selectively into plasma and comprised approximately 32%
      of total astaxanthin 6-7.5 h postprandially. The proportion of all-E-astaxanthin
      was significantly higher in the very low density lipoproteins and chylomicrons
      (VLDL/CM) plasma lipoprotein fraction than in the high density lipoproteins (HDL)
      and low denisty lipoproteins (LDL) fractions (P<0.05). The results indicate that
      a selective process increase the relative proportion of astaxanthin Z-isomers
      compared to the all-E-astaxanthin before uptake in blood and that the astaxanthin
      esters are hydrolyzed selectively during absorption.

PMID- 15556072
TI  - Do organisms living around hydrothermal vent sites contain specific
      metallothioneins? The case of the genus Bathymodiolus (Bivalvia, Mytilidae).
AB  - The unusual characteristics of the hydrothermal vent environment (high pressure
      and metal concentrations, low pH, etc.) leads us to wonder how species living in
      this particular biotope have adjusted to these severe living conditions. To
      investigate the consequences of high metal concentrations, filter-feeding
      organisms are commonly used in ecotoxicological studies. Metallothioneins (MTs)
      are proteins conserved throughout the animal kingdom and involved in
      intracellular metal regulation. Therefore, we tried here to find out whether the
      metallothioneins of hydrothermal bivalves are different from those of coastal
      bivalves. The characterization of DNA sequences coding MTs from some of the most
      common hydrothermal bivalves, belonging to the genus Bathymodiolus (Mytilidae)
      was performed by reverse transcription polymerase chain reactions (RT-PCRs). The
      complementary DNAs (cDNAs) of MT-10 and MT-20 isoforms were obtained for the
      Atlantic and Pacific hydrothermal mussels (Bathymodiolus azoricus and
      Bathymodiolus thermophilus). The MT-10 transcripts were 222 nucleotides long and
      the MT-20 transcripts, 207 nucleotides. The polymorphism of the MT cDNAs in these
      two hydrothermal species is discussed. The comparison between metallothionein
      cDNA sequences of the Mytilus and the Bathymodiolus genera shows strong
      homologies among metallothioneins of coastal and hydrothermal mussels.

PMID- 15556073
TI  - Regulation of collagen prolyl 4-hydroxylase and matrix metalloproteinases in
      fibrosarcoma cells by hypoxia.
AB  - The cellular response to hypoxia is characterized by an enhanced deposition of
      extracellular matrix (ECM) components, mainly collagens. Collagen homeostasis is
      determined by the rate of synthesis and degradation. In this study, we
      investigated the synthesis of enzymes of collagen metabolism like collagen prolyl
      4-hydroxylase (P4H), matrix metalloproteinases (MMP-2 and MMP-9) and their
      regulatory factors MT1-MMP, TIMP-1 and TIMP-2 in HT1080 fibroblasts under the
      influence of hypoxia. The results indicate that hypoxia affects collagen
      homeostasis in a biphasic manner concerning basic mechanisms of gene expression.
      P4H-alpha subunits are up-regulated at the transcriptional and translational
      level, whereas the beta-subunit is not susceptible to hypoxia. MMP-9 is primarily
      regulated at the transcriptional and translational level, whereas MMP-2 is mainly
      controlled by proteolytic activation of the proenzyme. Our results suggest that
      short-term hypoxia facilitates fibrosis in HT1080 cells by activation of P4H
      alpha expression and inhibition of the synthesis of MMPs. Under long-term
      hypoxia, however, anti-fibrotic mechanisms prevail. Although P4H-alpha expression
      sustains at a high level, collagenolytic activities dominate by abolishing
      inhibition of synthesis and activity of MMPs.

PMID- 15556074
TI  - Binding of xenoestrogens to the sex steroid-binding protein in plasma from Arctic
      charr (Salvelinus alpinus L.).
AB  - A specific sex steroid-binding protein (SBP) is believed to be involved in
      regulation of circulating sex steroids, steroid delivery to target cells and
      intracellular signalling in sex steroid-sensitive tissues. In the present work,
      interactions between xenoestrogens and the plasma SBP in Arctic charr (Salvelinus
      alpinus L.) were determined using ligand-protein binding studies. The test
      compounds were all able to displace tritiated 17 beta-estradiol (E2) from the
      Arctic charr SBP (acSBP) in a competitive and dose-dependent manner. The acSBP
      affinities for the xenoestrogens ranged over several orders of magnitude (17 beta
      estradiol>>ethynylestradiol (EE2)>zearalenone (ZEA)>diethylstilbestrol
      (DES)>genistein (GEN)>bisphenol A (BPA), 4-t-octylphenol (OP)>>o,p'-DDT, and
      dieldrin (DIN)), but were consistently lower than that of 17 beta-estradiol
      (about 4 x 10(2) -10(6)-fold less potent). The relative binding affinity (RBA)
      for selected chemicals were independent of both gender, age and maturation
      status, as well as variations of acSBP binding affinity. The affinity of
      endogenous steroids and estrogen mimics for the acSBP shows a high correlation to
      the affinity for the rainbow trout SBP, thus suggesting a phylogenetically
      conserved ligand-binding site between closely related species. Furthermore, it is
      argued that interaction with the acSBP- and SBP-mediated processes may introduce
      novel pathways for endocrine disruption, which may work in concert with the
      classical receptor-mediated effects.

PMID- 15556075
TI  - Hematological responses of the Neotropical teleost matrinxa (Brycon cephalus) to
      environmental nitrite.
AB  - Environmental increase in nitrite impairs the function of several aquatic
      species, including fishes. Nitrite reacts with hemoglobin yielding the non
      functional methemoglobin (metHb), and many physiological disturbances can arise.
      The physiological mechanisms to cope with nitrite are still unclear in fish.
      Hematological parameters, the role of NADH-methemoglobin reductase system and the
      electrolytic balance were studied in the freshwater teleost Brycon cephalus
      (matrinxa) exposed to 0.2, 0.4 and 0.6 mg/L of nitrite N-NO(2) for 24 and 96 h.
      Hematocrit, total hemoglobin and the red blood cell (RBC) number decreased.
      Methemoglobin content increased from 1% to 69% for 24 h of exposure and
      drastically from 5-6% to 90% for 96 h. The activity of NADH-methemoglobin
      reductase system displayed a tendency of increase in response to nitrite
      concentration or time of exposure. In the plasma, nitrite was accumulated to
      values 30-fold higher than the environmental concentration. The plasma K(+)
      concentration increased only in fish exposed to NO(2) for 24 h. No changes in
      plasma protein and Na(+) were observed during nitrite exposure but Cl-presented a
      punctual increase at 0.2 mg/L N-NO(2)-96 h. The hematological data suggest that
      nitrite caused functional and hemolytic anemia. Furthermore, the electrolytic
      balance was relatively undisturbed, and the nitrite clearance in matrinxa is
      likely depending on other factors than NADH-methemoglobin reductase system.

PMID- 15556076
TI  - Effects of phytochemicals of Flemingia vestita (Fabaceae) on glucose 6-phosphate
      dehydrogenase and enzymes of gluconeogenesis in a cestode (Raillietina
      echinobothrida).
AB  - The crude root-peel extract of Flemingia vestita, containing genistein as the
      major isoflavone, has a vermifugal/vermicidal effect. It acts by causing flaccid
      paralysis accompanied by alterations in the activities of several tegumental
      enzymes and other metabolic activities in the fowl tapeworm, Raillietina
      echinobothrida. To elucidate the mode of action of the putative phytochemicals on
      energy metabolism, crude root-peel extract, pure genistein and praziquantel were
      tested on glucose 6-phosphate dehydrogenase (G6PDH) and enzymes of
      gluconeogenesis--pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase
      (PEPCK) and fructose 1,6-bisphosphatase (FBPase)--in R. echinobothrida. The
      activities of G6PDH, PEPCK and FBPase were largely restricted to the cytosolic
      fraction, while PC was confined to the mitochondrial fraction. Following
      treatments, the G6PDH activity was decreased by 23-31%, whereas the activities of
      PC and PEPCK were increased by 32-44% and 44-49%, respectively. There was no
      significant effect by any of the treatments on FBPase activity. We hypothesize
      that the phytochemicals from F. vestita, genistein in particular, influence the
      key enzymes of these pathways, which is perhaps a function of high energy demand
      of the parasite under anthelmintic stress.

PMID- 15556077
TI  - Survey of estrogenic activity in fish feed by yeast estrogen-screen assay.
AB  - Fishes have been used as laboratory animal for research of estrogenic endocrine
      disrupters by many researchers. However, much less attention was paid to the
      possibility that compounds with estrogenic activity are present in fish diets. In
      order to examine this possibility, we measured the estrogenic activity in
      commercial fish feed by in vitro yeast estrogen-screen (YES) assay based on the
      binding ability of tested compounds to estrogen receptors. Estrogenic activity
      was detected in all the commercial fish feed examined (0.2-6.2 ng estradiol
      equivalent/g fish feed), some phytoestrogens (genistein, formononetin, equol and
      coumestrol; relative activity to estradiol, 8.6 x 10(-6)-1.1 x 10(-4) by giving a
      value of 1.0 to estradiol) and some androgens (testosterone, 11-ketotestosterone
      and 5 alpha-dihydrotestosterone; relative activity to estradiol, 3.0 x 10(-6)-1.2
      x 10(-4)). Therefore, it is possible that these compounds could affect the
      results of in vivo estrogen assay, such as vitellogenin production in male fish,
      especially when fish are fed commercial feed.

PMID- 15556078
TI  - Oxidative stress and antioxidant defenses after prolonged starvation in Dentex
      dentex liver.
AB  - The aim of this work was to evaluate the effects of prolonged starvation and
      refeeding on antioxidant status and some metabolic-related parameters in common
      dentex (Dentex dentex) liver. Fish deprived of food for 5 weeks showed a
      significant increase in lipid peroxidation, measured as malondialdehyde (MDA)
      levels. The activity of the antioxidative enzymes superoxide dismutase (SOD),
      catalase, and glutathione peroxidase (GPX) in starved fish significantly
      increased (by 42%, 22%, and 52%, respectively), whereas glutathione reductase
      (GR) activity was significantly depressed by 53% compared to controls. No
      qualitative changes in the SOD isoenzymatic pattern were detected by
      nondenaturing PAGE analysis, but the isoforms corresponding to CuZn-SOD I and II
      were enhanced in starved fish. The activity of the enzymes indicative of
      oxidative metabolism, beta-hydroxyacyl CoA dehydrogenase (HOAD) and citrate
      synthase (CS), significantly increased (by 123% and 28%, respectively), and that
      of glucose-6-phosphate dehydrogenase (G6PDH) was inhibited by 56%. Oxidative
      damage under these circumstances is reversible since all biomarkers assayed
      returned to control values after refeeding. Our results show that prolonged
      starvation leads to a pro-oxidant situation and oxidative stress despite
      activation of antioxidant defense mechanisms, and that inhibition of G6PDH
      activity might be responsible for this failure in cellular antioxidant defenses.

PMID- 15556079
TI  - Physiological effects of dietary cadmium acclimation and waterborne cadmium
      challenge in rainbow trout: respiratory, ionoregulatory, and stress parameters.
AB  - A suite of respiratory, acid-base, ionoregulatory, hematological, and stress
      parameters were examined in adult rainbow trout (Oncorhynchus mykiss) after
      chronic exposure to a sublethal level of dietary Cd (500 mg/kg diet) for 45 days
      and during a subsequent challenge to waterborne Cd (10 microg/L) for 72 h. Blood
      sampling via an indwelling arterial catheter revealed that dietary Cd had no
      major effects on blood gases, acid-base balance, and plasma ions (Ca(2+), Mg(2+),
      K(+), Na(+), and Cl(-)) in trout. The most notable effects were an increase in
      hematocrit (49%) and hemoglobin (74%), and a decrease in the plasma total ammonia
      (43%) and glucose (49%) of the dietary Cd-exposed fish relative to the nonexposed
      controls. Dietary Cd resulted in a 26-fold increase of plasma Cd level over 45
      days (approximately 24 ng/mL). The fish exposed to dietary Cd showed acclimation
      with increased protection against the effects of waterborne Cd on arterial blood
      P(aCO2) and pH, plasma ions, and stress indices. After waterborne Cd challenge,
      nonacclimated fish, but not Cd-acclimated fish, exhibited respiratory acidosis.
      Plasma Ca(2+) levels declined from the prechallenge level, but the effect was
      more pronounced in nonacclimated fish (44%) than in Cd-acclimated fish (14%) by
      72 h. Plasma K(+) was elevated only in the nonacclimated fish. Similarly,
      waterborne Cd caused an elevation of all four traditional stress parameters
      (plasma total ammonia, cortisol, glucose, and lactate) only in the nonacclimated
      fish. Thus, chronic exposure to dietary Cd protects rainbow trout against
      physiological stress caused by waterborne Cd and both dietary and waterborne Cd
      should be considered in determining the extent of Cd toxicity to fish.

PMID- 15556080
TI  - Toxicity of microcystin from cyanobacteria growing in a source of drinking water.
AB  - Microcystin-LR (MC-LR) is a cyanobacterial heptapeptide that presents acute and
      chronic hazards to animal and human health. The morphological changes in
      mitochondria are the primary effect induced by MC-LR leading to cell death. We
      investigated the toxicity of cyanobacterial microcystin-containing extract (CEM)
      on the respiratory complex of mammalian mitochondria from Bos taurus.
      Cyanobacterial blooms of Microcystis aeruginosa were harvested from Sulejow
      Reservoir, a source of drinking water in central Poland. The concentration of
      microcystin-LR (MC-LR(CEM)) in CEM extract was determined by high-performance
      liquid chromatography (HPLC). Commercially available microcystin-LR (Sigma) was
      used as a standard (MC-LR(S)); both standard and CEM extract were incubated with
      mitochondria in different doses and time of exposure. MC-RL(CEM) at 1 nM, maximal
      acceptable dose of microcystin (WHO) in drinking water, provoked activation of
      cytochrome c oxidase complex in mitochondria. We suggest that it might be
      considered as a defensive signal of mitochondria against low concentration of a
      toxic compound. In contrast 1 iM MC-RL(CME) inhibited the activity of
      mitochondrial oxidase complex much stronger than the same concentration of
      standard MC-RL(S) (58% vs. 87% of control activity, P<0.05), and this may cause a
      similar effect to long-term consumption of water. In conclusion, we affirm that
      CEM extract is highly toxic, and mitochondria could be used as an indicator of
      this toxicity in vivo, especially during long-term consumption of water from
      reservoirs where microcystin is produced.

PMID- 15556081
TI  - Elucidation of the role of Grr1p in glucose sensing by Saccharomyces cerevisiae
      through genome-wide transcription analysis.
AB  - The role of Grr1p in glucose sensing in Saccharomyces cerevisiae was elucidated
      through genome-wide transcription analysis. From triplicate analysis of a strain
      with deletion of the GRR1-gene from the genome and an isogenic reference strain,
      68 genes were identified to have significantly altered expression using a
      Student's t-test with Bonferroni correction. These 68 genes were widely
      distributed across different parts of the cellular metabolism and GRR1-deletion
      is therefore concluded to result in polytrophic effects, indicating multiple
      roles for Grr1p. Using a less conservative statistical test, namely the SAM test,
      232 genes were identified as having significantly altered expression, and also
      these genes were widely distributed across different parts of the cellular
      metabolism. Promoter analyses on a genome-wide scale and on the genes with
      significant changes revealed an over-representation of DNA-binding motifs for the
      transcriptional regulators Mig1p and Rgt1p in the promoter region of the
      significantly altered genes, indicating that Grr1p plays an important role in the
      regulatory pathways that ultimately lead to transcriptional regulation by each of
      the components Mig1p and Rgt1p.

PMID- 15556082
TI  - Ability of human CDC25B phosphatase splice variants to replace the function of
      the fission yeast Cdc25 cell cycle regulator.
AB  - CDC25 phosphatases are essential and evolutionary-conserved actors of the
      eukaryotic cell cycle control. To examine and compare the properties of three
      splicing variants of human CDC25B, recombinant fission yeast strains expressing
      the human proteins in place of the endogenous Cdc25 were generated and
      characterized. We report, that the three CDC25B variants: (i) efficiently replace
      the yeast counterpart in vegetative growth, (ii) partly restore the gamma and UV
      radiation DNA damage-activated checkpoint, (iii) fail to restore the DNA
      replication checkpoint activated by hydroxyurea. Although these yeast strains do
      not reveal the specific functions of the human CDC25B variants, they should
      provide useful screening tools for the identification of new cell cycle
      regulators and pharmacological inhibitors of CDC25 phosphatase.

PMID- 15556083
TI  - Two-dimensional protein map of an "ale"-brewing yeast strain: proteome dynamics
      during fermentation.
AB  - The first protein map of an ale-fermenting yeast is presented in this paper: 205
      spots corresponding to 133 different proteins were identified. Comparison of the
      proteome of this ale strain with a lager brewing yeast and the Saccharomyces
      cerevisiae strain S288c confirmed that this ale strain is much closer to S288c
      than the lager strain at the proteome level. The dynamics of the ale-brewing
      yeast proteome during production-scale fermentation was analysed at the beginning
      and end of the first and the third usage of the yeast (called generation in the
      brewing industry). During the first generation, most changes were related to the
      switch from aerobic propagation to anaerobic fermentation. Fewer changes were
      observed during the third generation but certain stress-response proteins such as
      Hsp26p, Ssa4p and Pnc1p exhibited constitutive expression in subsequent
      generations. The ale brewing yeast strain appears to be quite well adapted to
      fermentation conditions and stresses.

PMID- 15556084
TI  - Reactivation of the alternative oxidase of Yarrowia lipolytica by nucleoside
      monophosphates.
AB  - The study of the effect of nucleoside phosphates on the activity of cyanide
      resistant oxidase in the mitochondria and submitochondrial particles of Yarrowia
      lipolytica showed that adenosine monophosphate (5'-AMP, AMP) did not stimulate
      the respiration of intact mitochondria. The incubation of mitochondria at room
      temperature (25 degrees C) for 3-5 h or their treatment with ultrasound,
      phospholipase A, and the detergent Triton X-100 at a low temperature inactivated
      the cyanide-resistant alternative oxidase. The inactivated alternative oxidase
      could be reactivated with AMP. The reactivating effect of AMP was enhanced by
      azolectin. Some other nucleoside phosphates also showed reactivating ability in
      the following descending order: AMP = GMP > GDP > GTP > MP > IMP. The apparent
      K(m) values for AMP in reactivation of the alternative oxidase of
      submitochondrial particles or mitochondria treated with Triton X-100 and
      incubated at 25 degrees C were calculated. Physiological aspects of activation of
      the alternative oxidase are discussed in connection with the impairment of
      electron transfer through the cytochrome pathway.

PMID- 15556085
TI  - Enological and genetic traits of Saccharomyces cerevisiae isolated from former
      and modern wineries.
AB  - Saccharomyces cerevisiae strains isolated from two different wineries in central
      Italy were subjected to enological and molecular characterization to investigate
      the influence of the winery environment. One of the selected wineries is a
      modern, working winery, whereas the second one was abandoned since 1914 and was
      located in an artificial cavern. The results obtained by our analysis of the
      fermentation traits underline the selectivity of the winery environment (winery
      effect), since strains isolated from the industrial winery showed higher values
      for characters typically subjected to selective pressure, such as maximum
      capability to produce ethanol, fermentation rate and SO(2) resistance. Pulsed
      field gel electrophoresis (PFGE), random amplification of polymorphic DNA (RAPD)
      PCR and SAU-PCR were carried out to assesss genetic differences between the two
      populations studied. Only RAPD-PCR could distinguish between the two populations
      based on their provenience, whereas PFGE and SAU-PCR gave profiles shared between
      strains isolated from the industrial and former winery. Moreover, analysis of the
      karyotypes suggested the presence of chromosomal-length polymorphism; differences
      in the size and number of chromosomes between the two groups of isolates, as well
      as within each group, were observed.

PMID- 15556086
TI  - Characterization of an antifungal glycolipid secreted by the yeast
      Sympodiomycopsis paphiopedili.
AB  - An antifungal glycolipid was purified from the culture liquid of the
      ustilaginomycetous yeast Sympodiomycopsis paphiopedili by column and thin-layer
      chromatography. According to nuclear magnetic resonance and mass-spectroscopy
      experiments it was a cellobioside containing 2,15,16-trihydroxypalmitic acid as
      an aglycon. The minimal effective concentrations leading to ATP leakage and
      growth inhibition were 45 and 160 microg ml(-1) for Cryptococcus terreus and
      Candida albicans, respectively.

PMID- 15556087
TI  - Application of temperature gradient gel electrophoresis to the study of yeast
      diversity in the estuary of the Tagus river, Portugal.
AB  - Temperature gradient gel electrophoresis (TGGE) was employed for the assessment
      of yeast diversity in the estuary of the Tagus river (Portugal). The molecular
      detection of yeasts was carried out directly from water samples and, in parallel,
      a cultivation approach by means of an enrichment step was employed. A nested PCR
      was employed to obtain a fungal amplicon containing the D2 domain of the 26S rRNA
      gene. For identification the TGGE bands were extracted, re-amplified, and
      sequenced. Fourteen fungal taxa were detected and all except one were yeasts.
      Most yeast sequences corresponded to members of the Ascomycota and only three
      belonged to the Basidiomycota. Five yeasts (four ascomycetes and one
      basidiomycete) could not be identified to the species level due to the uniqueness
      of their sequences. The number of species detected after enrichment was higher
      than the number of taxa found using the direct detection method. This suggests
      that some yeast populations are present in densities that are below the detection
      threshold of the method. With respect to the analysis of the yeast community
      structure, our results indicate that the dominant populations belong to
      Debaryomyces hansenii, Rhodotorula mucilaginosa, Cryptococcus longus, and to an
      uncultured basidiomycetous yeast phylogenetically close to Cr. longus. The
      combined analysis of direct detection and cultivation approaches indicates a
      similar community structure at the two sampled sites since nine species were
      present at both localities.

PMID- 15556088
TI  - Molecular-genetic differentiation of the dairy yeast Kluyveromyces lactis and its
      closest wild relatives.
AB  - The currently accepted formal division of the species Kluyveromyces lactis into
      two taxonomic varieties, Kl. lactis var. lactis and Kl. lactis var.
      drosophilarum, is based arbitrarily on phenotypic and ecological characters. On
      the other hand, the genetic hybridisation analysis and molecular karyotyping of
      its synonyms allowed us [FEMS Yeast Res. 2 (2002) 39] to reinstate them in the
      genus Zygofabospora Kudriavzev emend G. Naumov (=Kluyveromyces Kurtzman et al.,
      2001) as the varieties Zf. lactis var. lactis, Zf. lactis var. krassilnikovii,
      Zf. lactis var. drosophilarum, Zf. lactis var. phaseolospora and Zf. lactis var.
      vanudenii. In the present work, we studied forty Kl. lactis strains of different
      geographic and ecological origins by means of restriction analysis of the PCR
      amplified non-coding nrDNA regions encompassing the intergenic spacer 2 (IGS2)
      and the internal transcribed spacers (ITS1 and ITS2). The results confirmed the
      complex structure of Kl. lactis. Moreover, four additional genetic populations
      were identified: three in North America ('aquatic', 'pseudovanudenii' and 'new')
      and one in Far-East Asia ('oriental'). Comparative sequence analysis of the 5.8S
      rRNA gene and the two internal transcribed spacers revealed that the populations
      'aquatic' and 'oriental' formed distinct taxa which are phylogenetically separate
      from the five known populations. However, some discrepancies were observed
      between the restriction and sequencing data. Genetic hybridisation analysis needs
      to be done to further elucidate the genetic relationships between the populations
      of Kl. lactis.

PMID- 15556089
TI  - Functional interaction in establishment of ribosomal integrity between small
      subunit protein rpS6 and translational regulator rpL10/Grc5p.
AB  - Functional ribosomes synthesize proteins in all living cells and are composed of
      two labile associated subunits, which are made of rRNA and ribosomal proteins.
      The rRNA of the small 40S subunit (SSU) of the functional eukaryotic 80S ribosome
      decodes the mRNA molecule and the large 60S subunit (LSU) rRNA catalyzes protein
      synthesis. Recent fine structure determinations of the ribosome renewed interest
      in the role of ribosomal proteins in modulation of the core ribosomal functions.
      RpL10/Grc5p is a component of the LSU and is a multifunctional translational
      regulator, operating in 60S subunit biogenesis, 60S subunit export and 60S
      subunit joining with the 40S subunit. Here, we report that rpL10/Grc5p
      functionally interacts with the nuclear export factor Nmd3p in modulation of the
      cellular polysome complement and with the small subunit protein rpS6 in subunit
      joining and differential protein expression.

PMID- 15556090
TI  - Cold-inducible selective degradation of peroxisomes in Hansenula polymorpha.
AB  - Exposure of Hansenula polymorpha cells, grown in batch cultures on methanol at 37
      degrees C, to a cold treatment (18 degrees C) is paralleled by a rapid
      degradation of peroxisomes present in these cells. Remarkably, the events
      accompanying organelle degradation at 18 degrees C are similar to those of
      selective glucose-induced peroxisome degradation in wild-type cells, described
      before. This observation was strengthened by the finding that cold-induced
      peroxisome degradation was not observed in mutants impaired in selective
      peroxisome degradation (Atg(-) mutants). Biochemical data indicated that the
      onset of peroxisome degradation was not triggered by the inactivation of
      peroxisome function due to the fall in temperature. We show that our findings
      have implications in case of fluorescence microscopy studies that are generally
      not conducted at physiological temperatures and thus may lead to strong
      morphological alterations unless proper precautions are taken.

PMID- 15556091
TI  - Transcriptional profiling of the early stages of germination in Candida albicans
      by real-time RT-PCR.
AB  - By using real-time RT-PCR, we profiled the expression of CGR1, CaMSI3, EFG1,
      NRG1, and TUP1 in Candida albicans strains JCM9061 and CAI4 under several
      conditions, including induction of morphological transition, heat shock, and
      treatment with calcium inhibitors. Expression of CaMSI3 changed under these
      growth conditions except during heat shock. CGR1 expression increased during the
      early stages of hyphal growth in JCM9061, while expression was strain-dependent
      during heat shock. Both EFG1 and NRG1 were similarly expressed under hypha
      inducing conditions and heat shock. Expression of TUP1 was slightly different
      from the expression of EFG1 or NRG1.

PMID- 15556092
TI  - Large heterogeneity of mutations in the gene encoding the low-density lipoprotein
      receptor in subjects with familial hypercholesterolaemia.
AB  - Molecular genetic testing for presymptomatic identification of subjects affected
      by familial hypercholesterolaemia (FH) is difficult due to the heterogeneity of
      the mutations in the gene encoding the low-density lipoprotein receptor (LDLR) in
      most populations. This investigation presents a detailed analysis of comparable,
      country-specific prevalence data of LDLR mutations in subjects with clinically
      defined FH and assesses the heterogeneous mutation diversity observed in most
      geographic regions.

PMID- 15556093
TI  - Mutation detection in patients with familial hypercholesterolaemia using
      heteroduplex and single strand conformation polymorphism analysis by capillary
      electrophoresis.
AB  - Mutations in the low-density lipoprotein receptor (LDLR) gene give rise to
      familial hypercholesterolaemia (FH). In this study we have used a 96-well
      capillary machine (MegaBACE, Amersham) to develop a single strand conformation
      polymorphism (SSCP) and heteroduplex method for the detection of mutations in the
      LDLR gene. We have applied this technique to 101 different mutations including
      single nucleotide polymorphisms in different exons of the LDLR gene. Hundred
      percent of these nucleotide alterations were distinguished by this method. We
      suggest this fast, reliable and safe method for diagnosis of FH in large patient
      groups.

PMID- 15556094
TI  - Genetic screening of patients with familial hypercholesterolaemia (FH): a New
      Zealand perspective.
AB  - Using denaturing high performance liquid chromatography (DHPLC) to screen the LDL
      receptor gene of people with familial hypercholesterolaemia (FH) in Christchurch,
      New Zealand, we have identified mutations in 65 patients (44 different mutations,
      of which 15 are novel). We also test family members of probands for the mutation
      identified in their relative, allowing diagnosis of affected children and those
      without classical FH symptoms. This screening programme is helpful to clinicians
      and benefits FH patients and their families, and has provided us with a pool of
      LDL receptor variants on which to base research into this disease.

PMID- 15556096
TI  - Vertebrate lungs: structure, topography and mechanics. A comparative perspective
      of the progressive integration of respiratory system, locomotor apparatus and
      ontogenetic development.
AB  - Vertebrate lungs are highly diverse in their structure, topographical position,
      ventilation mechanisms, constructional integration into the locomotor apparatus,
      and the interrelationships with the mode of their ontogenetic development.
      Vertebrate lungs evolved as supplementary air-breathing organs in primary fishes,
      being ventilated by buccal pumping. In most recent fishes the lungs are
      transformed into the hydrostatic swimbladder. This basic type of unicameral lungs
      and their buccal pumping ventilation are also found in recent amphibians. Land
      vertebrates developed a very efficient aspiration type of ventilation. In most
      recent reptiles the lungs are subdivided into three rows of lung chambers,
      enlarging the exchange surface in correlation to their increasing metabolic
      needs. The avian respiratory apparatus, with its volume-constant lungs and highly
      compliant air sacs, and the mammalian broncho-alveolar lung, with its very low
      compliance, are both derived from multicameral lungs. The avian and the mammalian
      respiratory systems are integrated very differently with the specific
      constructions of their locomotor apparatusses and the specific mode of their
      ontogenetic development.

PMID- 15556097
TI  - Reconstructing the evolution of the respiratory apparatus in tetrapods.
AB  - The structural type of a lung for animals that are derived from a single
      ancestral group can be characterized using extant phylogenetic bracketing.
      Functional morphological approximation can then be used to provide further
      information on the functional attributes. Combining information from diverse
      sources, plausible explanations are deduced for the respiratory apparatus of
      extinct species. The air-breathing apparatus of tetrapods has its origin in gill
      breathing. The lungs of the first tetrapods were probably long and consisted of a
      single series of parenchyma-filled chambers, arranged along an intrapulmonary
      duct. The duct gave rise to a broad central lumen in anurans. In amniotes a
      cartilaginous reinforcement evolved. The septate nature of the gas-exchange
      tissue (parenchyma) is recognizable in all tetrapods except birds. Active
      expiration began with the origin of transverse body wall musculature in
      amphibians, whereas active, negative-pressure inspiration is seen only in
      amniotes. The functional transition of trunk musculature from locomotor to
      respiratory is most complete in birds.

PMID- 15556098
TI  - Functional adaptation and its molecular basis in vertebrate hemoglobins,
      neuroglobins and cytoglobins.
AB  - Hemoglobin (Hb), the paradigm for allosteric proteins through decades, has gained
      renaissance in recent years following discovery of globins or their genes in all
      living organisms and in all tissues of higher animals, and of new members of the
      globin family, such as neuroglobins, Ngb, found predominantly in neural and nerve
      tissues and cytoglobins, Cygb, that has unprecedented nuclear location. The
      recent progresses in this field have been prompted by the development of
      sophisticated techniques to probe molecular structure and functions, which have
      revealed novel functions, such as the scavenging and release of vasoactive nitric
      oxide and the regulation of cellular metabolism. This review deals with the
      functional adaptations and the underlying molecular mechanisms in globins and
      presents case examples of molecular adaptations encountered in vertebrates and
      agnathans.

PMID- 15556099
TI  - Buffering and H+ ion dynamics in muscle tissues.
AB  - After anaerobic activity with release of large quantities of intermediary
      metabolic end products, further energy production critically depends on rapid
      elimination of H+ ions from the muscle tissues to secure key enzymatic
      activities. The involved processes, interactions and interrelationships of
      mechanisms have been analyzed on the basis of a physiological model and available
      experimental data. The H+ elimination from muscle tissue is a multifactorial
      process primarily governed by the capillary H+ transport capacitance, effected by
      buffering capabilities of intracellular and capillary fluids compartments, by
      dynamically interrelated regulation of intracellular and extracellular pH, by the
      magnitude and quality of convective perfusional transfer and further factors.
      Model calculations strongly resemble experimental data obtained in isolated
      perfused muscles and suggest that discrepancies between disparate literature data
      are attributable to experimental limitations.

PMID- 15556100
TI  - Surviving extreme lactic acidosis: the role of calcium lactate formation in the
      anoxic turtle.
AB  - During prolonged anoxia at low temperature, freshwater turtles develop high
      plasma concentrations of both lactate and calcium. At these concentrations the
      formation of the complex, calcium lactate, normally of little biological
      significance because of the low association constant for the reaction,
      significantly reduces the free concentrations of both lactate and calcium. In
      addition, lactate is taken up by the shell and skeleton to an extent that
      strongly indicates that calcium lactate formation participates in these
      structures as well. The binding of calcium to lactate thus contributes to the
      efflux of lactic acid from the anoxic cells and to the exploitation of the
      powerful buffering capacity of the shell and skeleton.

PMID- 15556101
TI  - pH regulation and swimbladder function in fish.
AB  - Gas gland cells of the European eel (Anguilla anguilla) are specialized for the
      production and secretion of acidic metabolites. Although typically exposed to
      high oxygen partial pressures, they convert glucose mainly into lactate, but also
      produce CO2 in the pentose phosphate shunt. Only a very small fraction of glucose
      is oxidized via aerobic metabolism. Although the buffer capacity of gas gland
      cells appears to be high, even at low extracellular pH values intracellular pH is
      always kept about 0.2-0.3 pH-units more acidic. Thus, under all physiological
      conditions proton concentration within gas gland cells is higher than in the
      extracellular fluid, facilitating proton extrusion. Diffusion of CO2, Na+/H+
      exchange, sodium-dependent anion exchange and a V-ATPase represent the pathways
      available for proton secretion. While under resting conditions the sodium
      dependent pathways and diffusion of CO2 appear to be the dominating mechanisms
      for acid secretion, at low intracellular pH the contribution of Na+/H+-exchange
      and of V-ATPase appear to increase, while sodium-dependent anion exchange becomes
      less important. The mechanisms regulating the activity of these acid-secreting
      pathways and of the metabolism responsible for the production of protons are
      largely unknown.

PMID- 15556102
TI  - Evolutionary trends in airway CO2/H+ chemoreception.
AB  - In many species of air-breathing vertebrates CO2-sensitive airway receptors play
      an important role in ventilatory control. In ectotherms, olfactory receptors
      often inhibit breathing and prolong breath holding when environmental CO2 levels
      are high. CO2/H+ sensitive pulmonary receptors (intra pulmonary chemoreceptors
      (IPC) and pulmonary stretch receptors (PSR)) regulate breathing patterns in all
      vertebrates in a manner that reduces dead space ventilation and enhances the
      efficiency of CO2 excretion under conditions of environmental hypercarbia, and/or
      reduces CO2 loss from hyperventilation. The greater CO2 sensitivity of IPC may
      allow them to also serve as a venous CO2 receptor (at least transiently when
      levels of metabolically produced CO2 begin to rise), prevent alkalosis during
      hyperpnea/polypnea, and may have contributed to the evolution of the extremely
      thin air/blood barrier and increased diffusion capacity associated with the rigid
      avian lung. The presence of all three receptor groups with different degrees of
      CO2 sensitivity in most reptiles, however, gives rise to what appear to be
      anomalous responses to environmental CO2.

PMID- 15556103
TI  - CO2 transduction mechanisms in avian intrapulmonary chemoreceptors: experiments
      and models.
AB  - Intrapulmonary chemoreceptors (IPC) are neurons that sense tonic and phasic CO2
      stimuli in the lungs of birds and diapsid reptiles. IPC are different from most
      other vertebrate respiratory CO2 receptors because: (1) they are stimulated by
      low PCO2 and inhibited by high PCO2, (2) they have extremely rapid response
      characteristics, (3) their CO2 sensitivity is nearly abolished by intracellular
      inhibitors of carbonic anhydrase, and (4) their CO2 sensitivity is strongly
      depressed by inhibiting Na+/H+ antiport exchange. Experimental evidence suggests
      that IPC respond to intracellular pH, not CO2 directly, and that intracellular pH
      and IPC discharge are determined by a kinetic balance between CO2
      hydration/dehydration rates, transmembrane acid/base exchange rates, and
      intracellular buffering. We review experimental evidence for and against various
      mechanisms of IPC CO2 chemotransduction, present a conceptual and mathematical
      model of the proposed mechanisms, and compare this model to CO2 transduction in
      other respiratory chemoreceptors.

PMID- 15556104
TI  - Eat and run: prioritization of oxygen delivery during elevated metabolic states.
AB  - The principal function of the cardiopulmonary system is the matching of oxygen
      and carbon dioxide transport to the metabolic requirements of different tissues.
      Increased oxygen demands (VO2), for example during physical activity, result in a
      rapid compensatory increase in cardiac output and redistribution of blood flow to
      the appropriate skeletal muscles. These cardiovascular changes are matched by
      suitable ventilatory increments. This matching of cardiopulmonary performance and
      metabolism during activity has been demonstrated in a number of different taxa,
      and is universal among vertebrates. In some animals, large increments in aerobic
      metabolism may also be associated with physiological states other than activity.
      In particular, VO2 may increase following feeding due to the energy requiring
      processes associated with prey handling, digestion and ensuing protein synthesis.
      This large increase in VO2 is termed "specific dynamic action" (SDA). In
      reptiles, the increase in VO2 during SDA may be 3-40-fold above resting values,
      peaking 24-36 h following ingestion, and remaining elevated for up to 7 days. In
      addition to the increased metabolic demands, digestion is associated with
      secretion of H+ into the stomach, resulting in a large metabolic alkalosis
      (alkaline tide) and a near doubling in plasma [HCO3-]. During digestion then, the
      cardiopulmonary system must meet the simultaneous challenges of an elevated
      oxygen demand and a pronounced metabolic alkalosis. This paper will compare and
      contrast the patterns of cardiopulmonary response to similar metabolic increments
      in these different physiological states (exercise and/or digestion) in a variety
      of reptiles, including the Burmese python, Python morulus, savannah monitor
      lizard, Varanus exanthematicus, and American alligator Alligator mississipiensis.

PMID- 15556105
TI  - Breathing in thin air: acclimatization to altitude in ducks.
AB  - We measured ventilation (VI) and arterial blood gases in Pekin ducks during
      acclimatization to 3800 m altitude for 1-90 days. Four experimental series were
      conducted over 4 years using both natural altitude and a hypobaric chamber. PaCO2
      decreased to 3.5 Torr, relative to the value measured during acute hypoxia after
      1 day and remained at this level for up to 90 days. However, PaO2 did not
      increase. Arterial pH showed an unexpected metabolic alkalosis during the first
      hours at altitude but after 3 days, a metabolic acidosis partially compensated
      the respiratory alkalosis and pHa was constant thereafter. When normoxia was
      restored after hypoxia, PaCO2 was 5.5 Torr less than the original normoxic
      control value, but PaO2 was not increased. VI showed variable changes during
      acclimatization but if metabolic rate was constant in our study, as reported by
      others, then effective parabronchial V(VP) increased during acclimatization.
      Increased VP tends to restore PaO2 toward normoxic levels and decreases adverse
      effects of gas exchange limitation, which apparently increased during
      acclimatization in ducks.

PMID- 15556106
TI  - Woodpecker cavity aeration: a predictive model.
AB  - We studied characteristics of the Syrian woodpecker (Dendrocopos syriacus)
      cavities in the field and a laboratory model, and rates of gas exchange in the
      laboratory. Night temperature of occupied cavities is 4.3 degrees C higher than
      empty ones, representing energy savings of approximately 24%. Oxygen conductance
      (GNO2) of an empty cavity is 7.1 ml[STPD] (Torr h)(-1), and is affected by winds
      at velocities up to 0.8 m/s. Day and night body temperatures were 42.0 and 40.1
      degrees C, respectively. Steady-state O2 consumption rates (MO2) were 3.49 +/-
      0.49 and 2.53 +/- 0.26 ml[STPD] (g h)(-1) during day and night respectively --
      higher than predicted by allometry. A mathematical model describing PO2 in a
      cavity, taking into consideration MO2, GNO2, heat convection and wind speed, from
      the moment birds inhabit it, was developed. It shows that on the average, one
      woodpecker staying in its cavity at night does not encounter hypoxic conditions.
      However, in nest cavities with below the average GNO2, with more inhabitants
      (e.g. during the breeding season), hypoxia may become a problem.

PMID- 15556107
TI  - Why savannah monitor lizards hyperventilate during activity: a comparison of
      model predictions and experimental data.
AB  - The functional and structural factors that limit maximal oxygen uptake (VO2 max)
      in lizards are not completely understood. Using an integrative model describing
      the interactive nature of the individual oxygen transport conductances, we
      performed an analysis of the oxygen transport system in the highly aerobic lizard
      Varanus exanthematicus with specific reference to the sensitivity of VO2 max to
      potential limitations in the ventilatory system. Our analysis predicts that DLO2
      must increase more than three-fold at VO2 max and even with this increase in DLO2
      , the VO2 max may be sensitive to factors that alter lung ventilation and/or
      lower lung PO2. To test the predictions of the model analysis, we experimentally
      determined the effects of reducing inspired O2 on VO2 max during treadmill
      exercise. We conclude from both our theoretical and experimental analyses that V.
      exanthematicus operates near the functional limits of its lung.

PMID- 15556108
TI  - The effect of O2 and CO2 on the dive behavior and heart rate of lesser scaup
      ducks (Aythya affinis): quantification of the critical PaO2 that initiates a
      diving bradycardia.
AB  - Lesser scaup ducks were trained to dive for short and long durations following
      exposure to various gas concentrations to determine the influence of oxygen (O2)
      and carbon dioxide (CO2) on diving behavior and heart rate. Compared with
      normoxia, hyperoxia (50% O2) significantly increased the duration of long dives,
      whereas severe hypoxia (9% O2) significantly decreased the duration of both short
      and long dives. Hypercapnia (5% CO2) had no effect on dive duration. Surface
      intervals were not significantly altered by the oxygen treatments, but
      significantly increased following CO2 exposure. Heart rate during diving was
      unaffected by hyperoxia and hypercapnia, but gradually declined in long dives
      after severe hypoxia. Thus, our results suggest that during the majority of
      dives, O2 and CO2 levels in lesser scaup ducks are managed through changes in
      diving behavior without any major cardiovascular adjustments, but below a
      threshold PaO2, a bradycardia is evoked to conserve the remaining oxygen for
      hypoxia sensitive tissues. A model of oxygen store utilization during voluntary
      diving was developed to estimate the critical PaO2 below which bradycardia is
      initiated (approximately 26 mmHg) and predicted that this critical PaO2 would be
      reached 19s into a dive after exposure to severe hypoxia, which corresponded
      exactly with the time of initiation of bradycardia in the severe hypoxia trials.

PMID- 15556109
TI  - Hypoxic pulmonary vasoconstriction is heterogeneously distributed in the prone
      dog.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is thought to protect gas exchange by
      decreasing perfusion to hypoxic regions. However, with global hypoxia, non
      uniformity in HPV may cause over-perfusion to some regions, leading to high
      altitude pulmonary edema. To quantify the spatial distribution of HPV and
      regional PO2 (PRO2) among small lung regions (approximately 2.0 cm3), five prone
      beagles (approximately 8.3 kg) were anesthetized and ventilated (PEEP
      approximately 2 cm H2O) with an F1O2 of 0.21, then 0.50, 0.18, 0.15, and 0.12 in
      random order. Regional blood perfusion (Q), ventilation (VA) and calculated PRO2
      were obtained using iv infusion of 15 microm and inhalation of 1 microm
      fluorescent microspheres. Lung pieces were clustered by their relative blood flow
      response to each F1O2. Clusters were shown to be spatially grouped within animals
      and across animals. Lung piece resistance increased as PRO2 decreased to 60-70
      mmHg but dropped at PRO2's < 60mmHg. Regional ventilation changed little with
      hypoxia. HPV varied more in strength of response, rather than PRO2 response
      threshold. In initially homogeneous VA/Q lungs, we conclude that HPV response is
      heterogeneous and spatially clustered.

PMID- 15556111
TI  - The reality of comorbidity: depression and drug abuse.

PMID- 15556110
TI  - Priority actions to improve the care of persons with co-occurring substance abuse
      and other mental disorders: a call to action.

PMID- 15556112
TI  - Alcohol use disorders and mood disorders: a National Institute on Alcohol Abuse
      and Alcoholism perspective.

PMID- 15556113
TI  - Co-occurring disorders and achieving recovery: the substance abuse and mental
      health services administration perspective.

PMID- 15556114
TI  - The conundrum of co-occurring mental and substance use disorders: opportunities
      for research.

PMID- 15556115
TI  - Why are we here? A patient's perspective on living with an untreated dual
      diagnosis.

PMID- 15556116
TI  - Dual diagnosis: the Depression And Bipolar Support Alliance's Patient
      Perspective.

PMID- 15556117
TI  - The epidemiology of dual diagnosis.
AB  - The English language literature on the epidemiology of dual diagnosis is
      reviewed. The literature shows mental disorders to be significantly related to
      alcohol and drug use disorders. The strongest associations involve externalizing
      mental disorders and alcohol-drug dependence. Mental disorders are associated
      with alcohol-drug use, problems among users, dependence among problem users, and
      persistence among people with lifetime dependence. These dual diagnoses are
      associated with severity and persistence of both mental and alcohol-drug
      disorders. A wider range of mental disorders is associated with nicotine
      dependence. Most people with dual diagnosis report their first mental disorder
      occurred at an earlier age than their first substance disorder. Prospective
      studies confirm this temporal order, although significant predictive associations
      are reciprocal. Analyses comparing active and remitted mental disorders suggest
      that some primary mental disorders are markers and others are causal risk factors
      for secondary substance disorders. The article closes with a discussion of ways
      epidemiologic research can be used to help target and evaluate interventions
      aimed at preventing secondary substance use disorders by treating early-onset
      primary mental disorders.

PMID- 15556118
TI  - Bipolar disorder and substance abuse.
AB  - Substance use disorders are overrepresented in individuals with bipolar and
      bipolar spectrum disorders. Although awareness of this phenomenon has increased
      over the past 20 years, few empirically based treatment strategies have been
      developed for this challenging patient population. This review examines the
      relationship between bipolar and substance use disorders and treatment options
      that have been studied in this patient population. First, we examine the high
      prevalence rates of substance use disorders in individuals diagnosed with bipolar
      disorder, the common problems associated with establishing a bipolar disorder
      diagnosis in individuals who abuse substances, the possible explanations for the
      frequent coexistence of bipolar and substance use disorders, and the negative
      effect of substance abuse on the course of and treatment outcomes for bipolar
      disorder. The review then focuses on treatment approaches for this patient
      population, including integrated group therapy for co-occurring bipolar and
      substance use disorders and pharmacotherapies that target both disorders.
      Finally, we present suggestions for medications that might be tested for their
      efficacy in treating both disorders in specific subgroups of patients with
      bipolar and substance use disorders.

PMID- 15556119
TI  - Three-year outcomes of long-term patients with co-occurring bipolar and substance
      use disorders.
AB  - Little is known about the long-term outcomes of patients in the public mental
      health system who are disabled by co-occurring bipolar and substance use
      disorders. This article reports on the 3-year course of 51 patients with co
      occurring bipolar and substance use disorders in the New Hampshire Dual Diagnosis
      Study. Participants received integrated dual disorders treatments in the state
      mental health system and were independently assessed with standardized measures
      at baseline and every 6 months for 3 years. Though psychiatric symptoms improved
      only modestly, participants improved steadily in terms of remission from
      substance abuse (61% in full remission at 3 years); they also achieved greater
      independent living (average 239 days in third year), competitive employment (49%
      in third year), regular social contacts with nonsubstance abusers (46% at 3
      years), and quality of life (56% satisfied with life at 3 years). Different
      domains of outcome were only weakly related to each other. Long-term, disabled
      patients with co-occurring bipolar and substance use disorders have potential for
      remission from substance abuse and substantial improvements in functioning and
      quality of life.

PMID- 15556120
TI  - Clinicians' assessments of bipolar disorder and substance abuse as predictors of
      suicidal behavior in acutely hospitalized psychiatric inpatients.
AB  - BACKGROUND: Suicide is a major risk for those with bipolar disorder, a risk
      amplified by comorbid substance abuse in some, but not all, previous studies. To
      further explore the relationships of substance abuse, suicide, and bipolarity as
      they present in clinical practice, we analyzed standardized clinical data from a
      large acute psychiatric inpatient service. METHODS: Standardized clinical
      evaluations of 7819 patients with diagnoses of bipolar depression (n=990),
      bipolar mania (n=948), unipolar depressive episode (n=3626), or schizophrenia
      schizoaffective disorders (n=2255) were analyzed to evaluate the relationship
      between current substance-use problems, substance-induced symptoms, and a current
      suicide crisis, as well as lifetime suicide attempts, with logistic regressions
      adjusting for age, gender, and ethnicity. RESULTS: Across the combined groups,
      current substance-use problems were significantly associated with a lifetime
      suicide attempt (odds ratios [ORs] 1.6-2.5) and to a lesser degree to the
      admission suicide crisis (ORs 1-2.2). Among bipolar (depressed/manic) patients,
      but not other diagnostic groups, those with both current substance-use problems
      and substance-induced symptoms had even higher rates of a recent suicide crisis
      (ORs 1.5-3.1) and of a lifetime attempt (ORs 2.5-3.4). CONCLUSIONS: In bipolar
      patients, substance use disorder doubled and substance use disorder plus
      substance-induced symptoms tripled the suicidal risk. Implications for future
      research are discussed.

PMID- 15556121
TI  - Contemporary addiction treatment: a review of systems problems for adults and
      adolescents.
AB  - There is national concern regarding the problems of alcohol and drug abuse and
      the adequacy and quality of the national addiction treatment system, particularly
      for adolescents. This article reviews the published literature evaluating the
      ability of health, education, and specialty treatment systems to identify and
      treat affected adolescents and adults. A separate section reviews the status of
      the national treatment system for adults through findings from a nationally
      representative survey of 175 specialty treatment programs. The findings are
      unambiguous and disturbing. Although substance abuse is prevalent in most
      schools, primary care practices, mental health clinics, and criminal justice
      agencies, there is insufficient training, organization, or reimbursement to
      screen, assess, and refer those with dependence or abuse disorders to appropriate
      services. There are too few programs available to treat those substance-dependent
      patients who are screened and significant barriers for patients attempting to
      enter those programs. Finally, the organizational, administrative, and personnel
      infrastructures of many treatment programs are fragile and unstable, making them
      unable to implement evidence-based care. These problems are serious in the adult
      system and even worse in the adolescent system. The article concludes with
      suggestions for improving systems integration to improve the quantity and quality
      of available care.

PMID- 15556122
TI  - New medication strategies for comorbid substance use and bipolar affective
      disorders.
AB  - Comorbidity of substance abuse disorders (SUD) with bipolar disorders (BPD) is a
      serious treatment problem. Childhood BPD can be further complicated by
      comorbidity with attention-deficit/hyperactivity disorder (ADHD) and later SUD
      during adolescence. The aim of this article is to review the literature on
      pharmacotherapies for these patients. Developing the ideal pharmacotherapy for
      BPD and SUD can be informed by the role of gamma-aminobutyric acid (GABA) in the
      neurobiology of SUD. This ideal pharmacotherapy would have several key
      characteristics. These characteristics include treating the BPD, relieving
      withdrawal symptoms, and preventing relapse to SUD. The ideal medication should
      have low abuse liability, require infrequent dosing, be well tolerated, and have
      few side effects. A medication approaching this ideal is the GABA enhancer
      valproate. Adding atypical antipsychotic agents might not improve valproate's
      efficacy, but combining GABA medications with selective serotonin reuptake
      inhibitors holds promise for SUD with depression. Pemoline might be the best
      option for minimizing the risk of SUD complicating comorbid ADHD with BPD.

PMID- 15556124
TI  - Antidepressant treatment of co-occurring depression and alcohol dependence.
AB  - The use of antidepressant pharmacotherapy to treat patients with co-occurring
      depression and alcohol dependence is controversial. There is a stigma attached to
      giving medications to alcohol-dependent persons. Also, empirical evidence is
      sparse and inconsistent, which discourages the use of antidepressants in these
      patients. Historically, it has been a challenge to accurately diagnose a
      depressive disorder in the presence of alcohol dependence. In addition, early
      clinical studies were fraught with methodological problems; however, improved
      diagnostic assessments are now available, and in the last decade, results from
      well-controlled trials appear to support the use of antidepressants in this
      patient population in the specific role of relieving depressive symptoms. The
      majority of these trials also demonstrate that antidepressants have relatively
      little impact on reducing heavy drinking in this patient population, even though
      the medications reduce depressive symptoms. Newer approaches to treating patients
      with co-occurring depression and alcohol dependence suggest adding to the
      antidepressant a pharmacotherapy that directly impacts drinking. The findings
      from this review better define the action of antidepressants in patients with co
      occurring depression and alcohol dependence as specific to reducing depressive
      symptoms, and these medications and their action on mood have little impact on
      treating the co-occurring alcohol dependence.

PMID- 15556123
TI  - Behavioral therapies for co-occurring substance use and mood disorders.
AB  - There has been marked progress in recent years in the development of effective
      behavioral therapies for substance use disorders and in the largely independent
      development of behavioral therapies for mood disorders. Until recently, however,
      there were few well-specified behavioral approaches that incorporated an
      integrated approach for individuals in whom these disorders co-occur. The
      emerging literature on the efficacy of several types of behavioral therapy for
      engaging individuals with co-occurring mood and substance use disorders in
      treatment, reducing substance use and affective symptoms, enhancing adherence,
      and preventing disengagement and relapse is reviewed, followed by discussion of
      the challenges likely to be met in integrating these behavioral approaches into
      clinical practice.

PMID- 15556125
TI  - Treatment of depression in patients with opiate dependence.
AB  - Depression is common among opiate-dependent patients and has been associated with
      worse prognosis. This article reviews the literature on treatment of depressive
      disorders and symptoms among patients with opiate dependence. Depression bears a
      complex relationship to opiate dependence and may represent an independent
      disorder or may be engendered by psychosocial stress or toxic and withdrawal
      effects of drugs. Primary treatments for opiate dependence (e.g., methadone or
      buprenorphine maintenance or residential treatment) are associated with
      substantial improvements in depression. Studies of antidepressant medications
      have produced mixed results, some positive but more negative. It is not clear
      what accounts for these differences, and more research is needed to determine how
      to select opiate-dependent patients most likely to benefit from antidepressants.
      Fewer studies have examined psychosocial or behavioral interventions, but some of
      these also show promise. The data suggest a stepped model of care in which
      depression is evaluated and observed during the outset of treatment for opiate
      dependence and if it does not improve, specific psychosocial interventions or
      antidepressant medications tried. Research is needed on such integrated models of
      care and treatment algorithms to determine their efficacy and cost effectiveness.

PMID- 15556126
TI  - Treatment of cocaine dependence and depression.
AB  - In common with all other classes of substance use disorders, cocaine dependence
      has been shown to be strongly associated with depression by community and
      clinical surveys. Diagnosing depression in cocaine abusers can be challenging
      because it is difficult to distinguish transient symptoms caused by cocaine from
      enduring depression syndromes. Nonetheless, both "substance-induced" and
      "independent" depression syndromes require clinical attention, especially when
      symptoms have been persistent and severe before entering treatment. Use of
      antidepressant medications for combined cocaine dependence and depression is
      supported by a preponderance of evidence from 4 randomized clinical trials (RCTs)
      that prospectively targeted both depression and cocaine dependence and 7 RCTs in
      which a post hoc analyses demonstrated efficacy in the subgroup of cocaine
      abusers with comorbid depression. Notably, most negative studies have evaluated
      SSRIs while positive studies have used agents such as desipramine or buproprion.
      A substantial clinical trials literature supports the efficacy of behavioral
      treatments for general populations of cocaine abusers and of patients with
      depression but few studies have addressed patients with both disorders. Treatment
      development and research are needed on models of care that truly integrate
      strategies for addressing both cocaine use and depression. Recent advances have
      paved the way for a new generation of research. These include validation of
      efficacious cocaine treatments, improved diagnostic methods, organization of the
      Clinical Trials Network and development of guidelines for managing methodological
      challenges posed by high rates of current medication use and polysubstance abuse
      in treatment entering cocaine abusers.

PMID- 15556127
TI  - How to train residents to identify and treat dual diagnosis patients.
AB  - Medical training has failed to address the needs of patients with comorbid
      substance use and psychiatric disorders. Addiction teaching is limited and often
      fails to change the negative attitudes of many physicians. In many psychiatry
      residencies, addiction training occurs on inpatient or detoxification units and
      the focus is on screening, detoxification, and referral. Most residents do not
      gain adequate experience in the long-term management of dual-diagnosis patients.
      Successful clinical care is based on three critical elements (the "clinician's
      triad"): an adequate knowledge base, a positive attitude toward the patient and
      the benefits of treatment, and a sense of responsibility for the clinical
      problem. The Boston University Psychiatry Residency has designed an addiction
      training program to address these three issues. In addition to a comprehensive
      addiction seminar series, there are several unique features. The required
      clinical rotation occurs in an outpatient dual-diagnosis clinic and permits
      residents to follow a caseload of patients for 12 months. Extensive experience is
      gained in motivational interviewing, cognitive behavioral therapy, and
      pharmacotherapy. Self-directed learning approaches are used to maximize the
      educational experience on services that lack addiction faculty. Guidelines are
      provided for establishing a similar program and for more effective approaches to
      resident teaching.

PMID- 15556128
TI  - The stability and flexibility of spatial categories.
AB  - Four experiments examined the flexibility and stability with which children and
      adults organize locations into categories based on their spatiotemporal
      experience with locations. Seven-, 9-, 11-year-olds, and adults learned the
      locations of 20 objects in an open, square box. During learning, participants
      experienced the locations in four spatiotemporally defined groups (i.e., four
      sets of nearby locations learned together in time). At test, participants
      attempted to place the objects in the correct locations without the aid of the
      dots marking the locations. Children and adults displaced the objects toward the
      corners of the box consistent with the organization they experienced during
      learning, suggesting that they used spatiotemporal experience to organize the
      locations into groups. Importantly, the pattern of organization remained the same
      following a long delay for all four age groups, demonstrating stability. For
      adults, this organization shifted after a new pattern of spatiotemporal
      experience was introduced, suggesting that adults' categories based on
      spatiotemporal experience are quite flexible. Children only exhibited flexibility
      when the new pattern of spatiotemporal organization was consistent with available
      perceptual cues, demonstrating that the flexibility with which children organize
      locations into categories is intimately tied to both remembered and perceptual
      sources of information.

PMID- 15556129
TI  - Belief-desire reasoning as a process of selection.
AB  - Human learning may depend upon domain specialized mechanisms. A plausible example
      is rapid, early learning about the thoughts and feelings of other people. A major
      achievement in this domain, at about age four in the typically developing child,
      is the ability to solve problems in which the child attributes false beliefs to
      other people and predicts their actions. The main focus of theorizing has been
      why 3-year-olds fail, and only recently have there been any models of how success
      is achieved in false-belief tasks. Leslie and Polizzi (Inhibitory processing in
      the false-belief task: Two conjectures. Developmental Science, 1, 247-254, 1998)
      proposed two competing models of success, which are the focus of the current
      paper. The models assume that belief-desire reasoning is a process which selects
      a content for an agent's belief and an action for the agent's desire. In false
      belief tasks, the theory of mind mechanism (ToMM) provides plausible candidate
      belief contents, among which will be a 'true-belief.' A second process reviews
      these candidates and by default will select the true-belief content for
      attribution. To succeed in a false-belief task, the default content must be
      inhibited so that attention shifts to another candidate belief. In traditional
      false-belief tasks, the protagonist's desire is to approach an object. Here we
      make use of tasks in which the protagonist has a desire to avoid an object, about
      which she has a false-belief. Children find such tasks much more difficult than
      traditional tasks. Our models explain the additional difficulty by assuming that
      predicting action from an avoidance desire also requires an inhibition. The two
      processing models differ in the way that belief and desire inhibitory processes
      combine to achieve successful action prediction. In six experiments we obtain
      evidence favoring one model, in which parallel inhibitory processes cancel out,
      over the other model, in which serial inhibitions force attention to a previously
      inhibited location. These results are discussed in terms of a set of simple
      proposals for the modus operandi of a domain specific learning mechanism. The
      learning mechanism is in part modular--the ToMM--and in part penetrable--the
      Selection Processor (SP). We show how ToMM-SP can account both for competence and
      for successful and unsuccessful performance on a wide range of belief-desire
      tasks across the preschool period. Together, ToMM and SP attend to and learn
      about mental states.

PMID- 15556130
TI  - Statistical clustering and the contents of the infant vocabulary.
AB  - Infants parse speech into word-sized units according to biases that develop in
      the first year. One bias, present before the age of 7 months, is to cluster
      syllables that tend to co-occur. The present computational research demonstrates
      that this statistical clustering bias could lead to the extraction of speech
      sequences that are actual words, rather than missegmentations. In English and
      Dutch, these word-forms exhibit the strong-weak (trochaic) pattern that guides
      lexical segmentation after 8 months, suggesting that the trochaic parsing bias is
      learned as a generalization from statistically extracted bisyllables, and not via
      attention to short utterances or to high-frequency bisyllables. Extracted word
      forms come from various syntactic classes, and exhibit distributional
      characteristics enabling rudimentary sorting of words into syntactic categories.
      The results highlight the importance of infants' first year in language learning:
      though they may know the meanings of very few words, infants are well on their
      way to building a vocabulary.

PMID- 15556131
TI  - Species comparison and pharmacological characterization of rat and human CB2
      cannabinoid receptors.
AB  - Pharmacological effects of cannabinoid ligands are thought to be mediated through
      cannabinoid CB1 and CB2 receptor subtypes. Sequence analysis revealed that rat
      and human cannabinoid CB2 receptors are divergent and share 81% amino acid
      homology. Pharmacological analysis of the possible species differences between
      rat and human cannabinoid CB2 receptors was performed using radioligand binding
      and functional assays. Pronounced species selectivity at the rat cannabinoid CB2
      receptor (50- to 140-fold) was observed with AM-1710 (3-(1,1-Dimethyl-heptyl)-1
      hydroxy-9-methoxy-benzo[c]chromen-6-one) and AM-1714 (3-(1,1-Dimethyl-heptyl)-1-9
      dihydroxy-benzo[c]chromen-6-one). In contrast, JWH-015 ((2-Methyl-1-propyl-1H
      indol-3-yl)-napthalen-1-yl-methanone) was 3- to 10-fold selective at the human
      cannabinoid CB2 receptor. Endocannabinoid ligands were more human receptor
      selective. Cannabinoid CB2 receptor antagonist, AM-630 ((6-Iodo-2-methyl-1-(2
      morpholin-4-yl-ethyl)-1H-indol-3-yl)-(4-methoxy-phenyl)-methanone) was more
      potent at the rat receptor in radioligand binding and functional assays than that
      of the human receptor. The findings of the pharmacological differences between
      the human and rat cannabinoid CB2 receptors in this study provide critical
      information for characterizing cannabinoid ligands in in vivo rodent models for
      drug discovery purpose.

PMID- 15556132
TI  - Echinacoside rescues the SHSY5Y neuronal cells from TNFalpha-induced apoptosis.
AB  - We investigated the neuroprotective effect of echinacoside, one of the
      phenylethanoids isolated from the stems of Cistanches salsa, a Chinese herbal
      medicine, on tumor necrosis factor-alpha (TNFalpha)-induced apoptosis in human
      neuroblastoma (SHSY5Y) cells. Treatment of cultured SHSY5Y cells with TNFalpha
      100 ng ml(-1) for 36 h stimulated apoptosis, as demonstrated by typical
      morphological changes, cell viability, DNA laddering, annexin-V binding,
      intracellular reactive oxygen species, mitochondrial membrane potential and
      caspase-3 activity. However, simultaneous treatment with echinacoside (1, 10 or
      100 microg ml(-1)) attenuated the TNFalpha-mediated apoptosis. The antiapoptotic
      action of echinacoside was partially dependent on antioxidative stress effects,
      maintenance of mitochondria function, inhibition of caspase-3 activity and was
      also associated with increasing the expression of the antiapoptotic protein Bcl2.
      Thus, echinacoside has the neuroprotective capacity to antagonize TNFalpha
      induced apoptosis in SHSY5Y cells and may be useful in treating some
      neurodegenerative diseases.

PMID- 15556133
TI  - Basal calcium entry in vascular smooth muscle.
AB  - Basal calcium leak into smooth muscle was identified 30 years ago yet remains
      poorly understood. We characterized this leak measuring 45Ca2+ uptake into
      cultured rat aortic smooth muscle cells. Wash solution (0 degrees C) containing
      lanthanum (3 mM) removed extracellular tracer and increased cellular 45Ca2+
      retention more effectively than EGTA (0.2 mM). Basal Ca2+ entry was 1.45 x 10(9)
      Ca2+ x cell(-1) x min(-1). This translated to approximately 250 micromol(-1) x
      min(-1) given cell volumes of 4-15 pl as determined by 3-D image reconstruction.
      Gadolinium (100 microM) blocked 80% of the leak and exhibited a biphasic
      concentration-response relation (IC50s=1 microM and 2 mM). Organic ion channel
      blockers also inhibited approximately 80% of the leak; 45% by nifedipine (10
      microM), 7% was exclusively blocked by SKF 96365 (1-[b-[3-(4
      Methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole) (50 microM) and 23% was
      exclusively sensitive to 2-aminoethoxy-diphenylborate (2-APB, 75 microM). Reverse
      transcriptase polymerase chain reaction revealed TrpC1, 4 and 6 mRNA, and we
      propose that 2-APB may selectively block TrpC4-containing channels. We conclude
      that basal Ca2+ entry is mainly due to a basal open probability of excitable Ca2+
      -channels.

PMID- 15556134
TI  - Characterization of functional effects of Z-338, a novel gastroprokinetic agent,
      on the muscarinic M1, M2, and M3 receptors expressed in Xenopus oocytes.
AB  - This study characterized the functional effects of a novel gastroprokinetic
      agent, N-[2-(diisopropylamino)ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-1,
      3-thiazole-4-carboxyamide monohydrochloride trihydrate (Z338), on the muscarinic
      M1, M2, and M3 receptors expressed in Xenopus oocytes using the two-electrode
      voltage clamp method. Z-338 did not produce by itself any currents in oocytes
      expressing muscarinic M1, M3 receptors or muscarinic M2 receptors/G protein-gated
      inward rectifying K+ channels (Kir3.1 channels). In oocytes expressing muscarinic
      M1 receptors, Z-338 inhibited the acetylcholine-induced Ca2+ -activated Cl-
      current with an IC50 of 1.8 microM. In oocytes expressing muscarinic M2
      receptors/Kir3.1 channels, Z-338 inhibited the acetylcholine-induced K+ currents
      with an IC50 of 10.1 microM, whereas in oocytes expressing muscarinic M3
      receptors, Z-338 did not inhibit the acetylcholine-induced Ca2+ -activated Cl-
      current in a concentration-dependent manner. These results indicate that Z-338 is
      a potent antagonist not for muscarinic M3 receptor but for both muscarinic M1 and
      M2 receptors. Thus, Z-338 is a gastrokinetic agent with a unique profile.

PMID- 15556135
TI  - Methoctramine analogues inhibit responses to capsaicin and protons in rat dorsal
      root ganglion neurons.
AB  - We have investigated the possibility that vanilloid receptors have a binding site
      for polyamines and determined the consequences of binding to such a site. Whole
      cell and single-channel patch-clamp recordings were used to investigate the
      effect of the tetraamine, methoctramine, and 16 of its analogues on capsaicin and
      proton induced responses of foetal rat dorsal root ganglion neurons. All but two
      methoctramine analogues inhibited responses to 10 microM capsaicin with IC50
      values in the range of 2-70 microM at a holding potential of -100 mV. Inhibition
      was generally non-competitive and voltage-dependent. Methoctramine at 10 microM
      reduced the single channel mean open time (>3-fold), but also increased the mean
      closed time (1.7-fold). Sustained responses to pH 5.4 were antagonized by
      methoctramine with similar potency to capsaicin responses. Similar data were
      obtained with adult rat dorsal root ganglion neurons. These data indicate that
      methoctramine analogues bind to vanilloid receptors to inhibit their function.

PMID- 15556136
TI  - Nitric oxide mediates cyclosporine-induced impairment of the blood-brain barrier
      in cocultures of mouse brain endothelial cells and rat astrocytes.
AB  - The present study was designed to clarify the involvement of nitric oxide (NO)
      signaling in the adverse effect of cyclosporine on the blood-brain barrier.
      Cyclosporine increased the permeability of sodium-fluorescein and the cellular
      accumulation of rhodamine 123, a substrate of P-glycoprotein, in mouse brain
      endothelial (MBEC4) cells. This effect was markedly enhanced two- to threefold
      when MBEC4 cells were cocultured with rat astrocytes or C6 glioma cells. Direct
      and continuous electrochemical measurement of NO demonstrated that cyclosporine
      dose-dependently increased histamine- and phenylephrine-evoked NO production in
      MBEC4 cells and astrocytes, respectively. A NO synthase inhibitor (NG-monomethyl
      L-arginine) blocked slightly and markedly cyclosporine-induced impairment of the
      endothelial barrier in the monolayer and coculture system, respectively. These
      findings suggest that cyclosporine impairs the brain endothelial barrier function
      by accelerating NO production in the brain endothelial and astroglial cells. This
      event may be interpreted as triggering the occurrence of cyclosporine
      neurotoxicity.

PMID- 15556137
TI  - Pharmacological characterization of rebamipide: its cholecystokinin CCK1 receptor
      binding profile and effects on Ca2+ mobilization and amylase release in rat
      pancreatic acinar cells.
AB  - We previously reported that rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)
      quinolinon-4-yl]-propionic acid) generated oscillations of intracellular Ca2+
      concentration ([Ca2+]i) probably through the activation of cholecystokinin type 1
      (CCK1) receptors in rat pancreatic acinar cells. Therefore, in the present study,
      we aimed to establish the pharmacological characteristics of rebamipide in rat
      pancreatic acinar cells. CCK-8S and rebamipide inhibited [125I]BH-CCK-8S binding
      to rat pancreatic acinar cell membranes with IC50 values of 3.13 nM and 37.7
      microM, respectively. CCK-8S usually evoked [Ca2+]i oscillations at
      concentrations lower than 50 pM, and it induced biphasic [Ca2+]i increases at
      higher concentrations. In contrast to CCK-8S, rebamipide only induced [Ca2+]i
      oscillations at all the concentrations we used in this study. In addition,
      rebamipide was shown to inhibit high concentrations of CCK-8S-induced biphasic
      increases in [Ca2+]i, suggesting that rebamipide might be a partial agonist at
      cholecystokinin CCK1 receptors. Although rebamipide induced [Ca2+]i oscillations
      by activating the cholecystokinin CCK1 receptors, rebamipide did not cause
      amylase release and only inhibited CCK-stimulated amylase release reversibly and
      dose-dependently. However, rebamipide did not inhibit carbachol-, vasoactive
      intestinal polypeptide (VIP)-, and forskolin-induced amylase releases. These data
      indicate that rebamipide functions as a partial agonist for Ca2+ -mobilizing
      action, and it is also an antagonist for the amylase-releasing action of CCK.

PMID- 15556138
TI  - Ursodeoxycholic acid inhibits endothelin-1 production in human vascular
      endothelial cells.
AB  - Endothelin-1 is known to be implicated in the pathogenesis of hepatobiliary
      diseases such as cirrhosis, especially in portal hypertension. This study aimed
      to investigate the effects of ursodeoxycholic acid on endothelin-1 production in
      human endothelial cells. The effects of ursodeoxycholic acid and its conjugates
      (tauroursodeoxycholic and glycoursodeoxycholic acids) on endothelin-1 production
      as well as nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs)
      were examined. The production of endothelin-1 and nitric oxide in culture medium
      was measured using enzyme-linked immunosorbent assay (ELISA) and the Griess
      method, respectively. Endothelin-1 and endothelial nitric oxide synthase (eNOS)
      mRNA expression were investigated by real-time quantitative reverse
      transcriptase/polymerase chain reaction (RT-PCR). Ursodeoxycholic acid (30-1000
      microM) inhibited endothelin-1 production in a concentration-dependent manner,
      and ursodeoxycholic acid at concentrations higher than 300 microM increased
      nitric oxide production in culture medium. The conjugates of ursodeoxycholic acid
      also increased nitric oxide production and decreased endothelin-1 production,
      which was less effective than ursodeoxycholic acid. N-nitro-L-arginine-mythel
      ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, suppressed the
      ursodeoxycholic acid-induced nitric oxide production, but it did not antagonize
      the inhibitory effects of ursodeoxycholic acid on endothelin-1 production.
      Ursodeoxycholic acid also induced a concentration-dependent decrease in
      endothelin-1 mRNA expression without significant changes in eNOS mRNA expression.
      These results provide novel evidence that ursodeoxycholic acid inhibits
      endothelin-1 production in human endothelial cells, but nitric oxide is not
      responsible for the inhibitory effect of ursodeoxycholic acid on endothelin-1.
      Thus, ursodeoxycholic acid therapy may prevent the development of several
      pathogenesis such as portal hypertension observed in patients with cirrhosis due
      to the improvement of endothelial function.

PMID- 15556139
TI  - Intrathecal clonidine inhibits mechanical allodynia via activation of the spinal
      muscarinic M1 receptor in streptozotocin-induced diabetic mice.
AB  - We examined the involvement of the spinal muscarinic receptors in the clonidine
      induced antiallodynic effects. Mechanical sensitivity was assessed by stimulating
      the hind paw with von Frey filaments. In streptozotocin-treated (200 mg/kg, i.v.)
      diabetic mice, hypersensitivity to mechanical stimulation appeared 3 days after
      streptozotocin administration, and persisted for 11 days. This mechanical
      hypersensitivity (allodynia) was inhibited by the intrathecal (i.t.) injection of
      clonidine. The muscarinic receptor antagonist atropine (i.t.) and alpha2
      adrenoreceptor antagonist yohimbine (i.t. or subcutaneous injection) abolished
      the antiallodynic effect of clonidine. The effect was mimicked by the muscarinic
      M1 receptor antagonist pirenzepine, but not by the muscarinic M2 receptor
      antagonist methoctoramine or the muscarinic M3 receptor antagonist 4-DAMP (4
      diphenyl-acetoxy-N-methylpiperidine methiodide). In addition, the mechanical
      hypersensitivity in diabetic mice was reduced by the selective muscarinic M1
      receptor agonist McN-A-343 (4-(m-chlorophenyl-carbamoyloxy)-2
      butynyltrimethylammonium chloride) (i.t.). These results suggest that spinal
      muscarinic M1 receptors participate in the antiallodynic effect of clonidine in
      diabetic mice.

PMID- 15556140
TI  - Protection by sustained release of physostigmine and procyclidine of soman
      poisoning in rats.
AB  - The efficacy of a combinational prophylactic regimen on the lethality,
      convulsions, and loss of morphological and functional integrities of the brain
      induced by an organophosphate soman was investigated in rats. The rats were
      implanted subcutaneously with osmotic minipumps containing the combinational
      prophylactic regimen composed of physostigmine, a reversible cholinesterase
      inhibitor, and procyclidine, an N-methyl-D-aspartate antagonist possessing
      anticholinergic action, for 3 days, and intoxicated subcutaneously with soman
      (160 microg/kg, 1.3 LD50). The doses of combinational regimen in minipumps were
      optimized to achieve 30-35% inhibition of blood cholinesterase activity by
      physostigmine and 50-100 ng/ml of blood concentrations of procyclidine as
      clinically available doses, respectively. In comparison, 1-[([4
      (aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium (HI
      6, 125 mg/kg) was administered intraperitoneally 30 min prior to the soman
      challenge in control groups to reduce mortality of rats without affecting
      convulsions. Soman induced profound limbic convulsions and 30% mortality, leading
      to increased blood-brain barrier permeability, neural injuries, learning and
      memory impairments, and physical incapacitation of survived rats pretreated with
      HI-6. The combinational regimen, at optimal doses without adverse effects on
      passive avoidance performances (72 microg/kg/h of physostigmine plus 432
      microg/kg/h of procyclidine), exerted full protective effects against lethality,
      convulsions, blood-brain barrier opening, brain injuries, learning and memory
      impairments, and physical incapacitation induced by soman. Taken together, it is
      suggested that the combination of physostigmine and procyclidine, at adequate
      doses, could be a choice to provide the victims of organophosphate poisoning with
      chance of intensive care for survival and neuroprotection.

PMID- 15556141
TI  - Passage of erythropoietic agents across the blood-brain barrier: a comparison of
      human and murine erythropoietin and the analog darbepoetin alfa.
AB  - Studies have suggested that erythropoietin (EPO) may be used to treat stroke in
      both animals and humans. It is thought to exert its effects directly on the brain
      and studies with therapeutic doses have shown that it can cross the blood-brain
      barrier. Here, we compared in a blinded fashion the ability of three
      erythropoietic agents (murine erythropoietin, human erythropoietin, and
      darbepoetin alfa, an analog of human erythropoietin in clinical use) to cross the
      blood-brain barrier of the mouse. High-performance liquid chromatography (HPLC)
      results showed that all three erythropoietic agents were enzymatically resistant
      in brain and blood. The unidirectional blood-to-brain influx rates (Ki) as
      measured by multiple-time regression analysis showed that all the erythropoietic
      agents crossed the blood-brain barrier at about the same rate as albumin,
      suggesting that they cross the blood-brain barrier by way of the extracellular
      pathways. No saturable component to influx was found, but indirect evidence
      suggested a brain-to-blood efflux system. The percent of the intravenously
      injected dose taken up per gram of brain (%Inj/g) ranged from 0.05 to 0.1 %Inj/g
      among the three erythropoietic agents and peaked about 3 h after IV injection.
      For other substances, this range of %Inj/g is known to produce direct effects on
      brain function. We conclude that erythropoietic agents cross the blood-brain
      barrier by way of the extracellular pathways in amounts that are likely
      sufficient to explain their neuroprotective effects.

PMID- 15556142
TI  - Effects on rat thalamic proteome by acute and subchronic MK-801-treatment.
AB  - Since the symptoms of intoxication with non-competitive N-methyl-D-aspartate
      (NMDA) receptor antagonists closely mimic symptoms in patients with
      schizophrenia, [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cycloheptene-5,10
      iminehydrogenmaleate (MK-801)-treated rodents are often used as a model for
      schizophrenia. In most studies, acute injections of MK-801 to rats have been
      used, but in some studies, longer periods of treatment have been performed. In
      our previous work, alterations in mRNA/protein expression were screened in the
      cerebral cortex of MK-801 treated rats. Different proteins were altered in
      different treatment courses of MK-801. The main objective of the present study
      was to evaluate different treatment periods of treatment with MK-801 in rats as a
      model for schizophrenia. Thalamus proteins from treated (acute, six and 12 days)
      and control rats were analyzed with two-dimensional gel electrophoresis and mass
      spectrometry. Our results show that different treatment times of MK-801 to rats
      give different biochemical results. Therefore, it is important to use the same
      treatment time in studies that will be compared.

PMID- 15556143
TI  - Lack of evidence of direct mitochondrial involvement in the neuroprotective
      effect of minocycline.
AB  - Minocycline has been reported to exert neuroprotection through inhibition of
      inflammatory processes and of mitochondrial cell death pathway. To further
      characterize the neuroprotective effect of minocycline, we determined its
      efficacy in different neuronal damage paradigms involving inflammation or
      mitochondrial dysfunction. In transient global ischaemia in gerbils, minocycline
      reduced hippocampal neuronal damage measured by peripheral type benzodiazepine
      binding sites density, a marker of microglial activation. The antiinflammatory
      properties of minocycline were confirmed on the model of carrageenan-induced paw
      oedema in rats. The use of two experimental animal models involving
      administration of mitochondrial toxins inhibiting a different complex of the
      mitochondrial respiratory chain permitted the exploration of the mitochondrial
      impact of minocycline. Although minocycline exhibited a marked efficacy in 1
      methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP; complex I inhibitor)-induced
      neurotoxicity in mice, it was ineffective in malonate (complex II inhibitor)
      induced striatal lesion in rats. In vitro investigations on energized
      mitochondria isolated from rat liver showed that minocycline (1 microM) did not
      inhibit the swelling induced by MPP+(1-methyl-4-phenylpyridinium). Moreover,
      higher concentrations of minocycline induced swelling. From these experiments,
      the neuroprotective activity of minocycline appears more related to its
      antiinflammatory activity than to a direct beneficial action on mitochondria.

PMID- 15556144
TI  - Nicergoline reverts haloperidol-induced loss of detoxifying-enzyme activity.
AB  - We evaluated the effects of nicergoline on antioxidant defense enzymes
      (detoxifying enzymes), during chronic treatment with haloperidol in rats. Chronic
      use of haloperidol (10 weeks, 1.5 mg/kg/day) induces a significant decrease in
      glutathione reductase, glutathione peroxidase and superoxide dismutase activity,
      in selected areas of the brain. Co-administration of nicergoline (20 days, 10
      mg/kg/day) significantly restored the activity of these enzymes to levels
      comparable to those observed in control rats. These observations suggest
      beneficial effects of nicergoline in the prevention and in the treatment of
      haloperidol-induced side effects.

PMID- 15556145
TI  - Discriminative stimulus effects of the structurally novel cannabinoid CB1/CB2
      receptor partial agonist BAY 59-3074 in the rat.
AB  - BAY 59-3074 [3-[2-cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1
      butane-sulfonate] is a structurally novel cannabinoid CB1/CB2 receptor partial
      agonist with analgesic properties. The present study was performed to confirm its
      receptor binding profile in a highly sensitive in vivo assay. Rats (n=10) learned
      to discriminate BAY 59-3074 (0.5 mg/kg, p.o., t-1 h) from vehicle in a fixed
      ratio: 10, food-reinforced two-lever procedure after a median number of 28
      training sessions. BAY 59-3074 generalized dose-dependently (ED(50): 0.081 mg/kg,
      p.o.) and the cue was detectable between 0.25 and 4 h after administration. The
      selective cannabinoid CB1 receptor antagonist SR 141716A [N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      hydrochloride] blocked the discriminative effects of BAY 59-3074 (ID50: 1.79
      mg/kg, i.p.). Complete generalization was also obtained after i.p. administration
      of BAY 59-3074 (ED50 value: 0.41 mg/kg), and the reference cannabinoids BAY 38
      7271 [(-)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1
      butanesulfonate, 0.011 mg/kg], CP 55,940 [(-)-cis-3-[2-hydroxy-4(1,1
      dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol, 0.013 mg/kg], HU
      210 [(-)-11-OH-Delta8-tetrahydrocannabinol dimethylheptyl, 0.022 mg/kg], WIN
      55,212-2 [(R)-4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1
      naphthalenylcarbonyl)-6H-pyrrolo [3,2,1-ij] quinolin-6-one, 0.41 mg/kg] and (-)
      Delta9-tetrahydrocannabinol (0.41 mg/kg). Non-cannabinoids with analgesic
      properties, such as morphine, amitriptyline, carbamazepine, gabapentin and
      baclofen, did not generalize to the cue. It is concluded that the discriminative
      stimulus effects of BAY 59-3074 are specifically mediated by cannabinoid CB1
      receptor activation.

PMID- 15556146
TI  - Drug interaction between methamphetamine and antihistamines: behavioral changes
      and tissue concentrations of methamphetamine in rats.
AB  - Methamphetamine is a psychomotor stimulant, whereas first generation
      antihistamines cause sedation. Several studies have demonstrated that first
      generation antihistamines potentiate methamphetamine-induced psychomotor
      activation and two possible mechanisms have been postulated. One is blockage of
      the central histaminergic neuron system and the other is inhibition of dopamine
      reuptake. However, the exact mechanism is still controversial. In this study, we
      examined in behavioral tests the effects of selected antihistamines on
      methamphetamine-induced psychomotor activation in rats, and measured plasma and
      brain tissue concentrations of methamphetamine. We found that some antihistamines
      significantly potentiate methamphetamine-induced psychomotor activation in rats
      and that plasma and brain tissue concentrations of methamphetamine in rats
      treated with methamphetamine in combination with D-chlorpheniramine were markedly
      higher than those in rats treated with methamphetamine alone. These results
      suggest that the potentiating effects of antihistamines are due to not only
      central effects but also the alteration of the pharmacokinetics of
      methamphetamine.

PMID- 15556147
TI  - Effect of MS-153 on the acquisition and expression of conditioned fear in rats.
AB  - Pavlovian fear conditioning is one of the most extensively studied and reliable
      behavioral paradigms used to investigate the mechanisms involved in fear and
      anxiety. Increased glutamatergic neurotransmission may play an important role in
      mediating fear conditioning. The present study assessed whether (R)-(-)-5-methyl
      1-nicotinoyl-2-pyrazoline (MS-153), a novel cerebroprotective agent that inhibits
      the release of glutamate and enhances glutamate uptake, affects the acquisition
      and expression of conditioned fear. The rats received administration of MS-153
      (i.p.) at 3, 10, and 30 mg/kg, 30 min before footshock and 24 h after footshock.
      Freezing behavior was measured in the chamber where they had previously received
      footshock for the acquisition experiments. For the expression experiments, the
      rats received MS-153 (i.p.) at the same doses 23.5 h after footshock and 30 min
      before expression testing. MS-153 significantly attenuated the acquisition and
      expression of freezing behavior. In addition, MS-153 administration did not
      affect locomotor activity. The present results suggest that extracellular
      glutamate is involved in fear conditioning, and that MS-153 has an anxiolytic
      effect by decreasing endogenous glutamate neurotransmission.

PMID- 15556148
TI  - Anandamide vehicles: a comparative study.
AB  - Among the studies that investigate the vasorelaxation induced by anandamide, one
      of the most frequent differences is the use of distinct solvents that could
      modify vascular function and explain the controversial results described. The
      aims of this study were: to evaluate the influence of different cannabinoid
      vehicles in vascular function of rat aorta, and to compare the vasorelaxation
      induced by anandamide dissolved in different vehicles. Vehicles were: ethanol
      (70%), Tween 80/ethanol (2:1 and 1:1), 1:1:18 (Tween 80/ethanol/saline) and
      dimethylsulphoxide (DMSO) 0.5%. All the vehicles tested, except DMSO 0.5%,
      modified the vascular and/or the endothelial function in rat aorta rings.
      Anandamide caused a time- and concentration-dependent vasorelaxation in all the
      experimental groups except in ethanol group, but the mechanisms involved in its
      vasorelaxation appear to be different depending on the vehicle used. The results
      obtained with vehicles containing Tween 80 suggest a non-endothelial component in
      the vasorelaxation caused by anandamide, while those obtained with DMSO at 0.5%
      suggest an endothelial component in this vasorelaxation.

PMID- 15556149
TI  - Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial
      stunning in anesthetized dogs.
AB  - Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during
      reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5
      difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor
      of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury
      (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of
      the left anterior descending coronary artery followed by a 4-h reperfusion in
      anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent
      segment shortening but remained depressed during a 4-h reperfusion period. A
      bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before
      reperfusion, improved significantly the recovery of percent segment shortening in
      the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and
      electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion
      induced change in coronary blood flow. These results suggest that the Na+/Ca2+
      exchanger is involved in the stunned myocardium of dogs after reperfusion, and
      that SEA0400 has a protective effect against myocardial stunning in dogs.

PMID- 15556150
TI  - Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary
      disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by an airways
      inflammation and by an enhanced generation of reactive oxygen species. The aim of
      our study was to assess the inflammation and the oxidative stress in airways of
      COPD patients with acute exacerbation of disease and in stability. Furthermore,
      we investigated the anti-inflammatory and antioxidant effects of 6 months
      treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We
      studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8
      isoprostane and Interleukine-6 were measured in their breath condensate through
      immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and
      Interleukine-6 were found in acute COPD patients compared to stable COPD and
      healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs.
      5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys
      showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5
      and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase
      of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of
      COPD patients compared to healthy controls especially during acute exacerbations
      of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect
      of short-term administration of SCMC-Lys in COPD, suggesting the importance of a
      further placebo-controlled study that should evaluate the effects of this drug.

PMID- 15556151
TI  - The role of nitric oxide on contractile impairment during endotoxemia in rat
      diaphragm muscle.
AB  - We examined the contribution of nitric oxide (NO) on the contractile impairment
      in diaphragm muscles of endotoxemic rats. Force-frequency relationship was
      depressed 24 h after lipopolysaccharide administration. 7-Nitroindazole,
      aminoguanidine and 1H-[1,2,4]Oxadiazole (4,3-a)quinoxalin-1-one (ODQ) partially
      restored the contractile impairment, Nomega-Nitro-L-Arginine (L-NNA) was
      ineffective. K+ contractions were reduced by 50% in endotoxemic muscles, 7
      nitroindazole partially recovered, while aminoguanidine and L-NNA were
      ineffective. Verapamil reduced contractility to a greater extent in endotoxemic
      muscles. Caffeine and ryanodine contractions were augmented during endotoxemia
      without NOS contribution. L-NNA, 7-nitroindazole, ODQ and hemoglobin did not
      affect, but aminoguanidine completely restored partially inhibited
      neurotransmission by d-tubocurarine. Endotoxemia did not change membrane
      potentials and neurotransmitter release but slightly increased excitability. At
      this stage of endotoxemia, (1) constitutive NOS appears to be the dominant
      isoform, (2) NO does not have a major role on contractile dysfunction and (3)
      impairment could be explained by altered sensitivity of the voltage sensor. (4)
      NO does not substantially modulate neuromuscular transmission in normal and
      endotoxemic rats.

PMID- 15556152
TI  - Angiogenesis, cell proliferation and apoptosis in gastric ulcer healing. Effect
      of a selective cox-2 inhibitor.
AB  - To elucidate the role of cyclooxygenase-2, we compared the effects of rofecoxib,
      a selective cyclooxygenase-2 inhibitor, and ibuprofen, a nonselective
      cyclooxygenase inhibitor, on the evolution of acetic-acid-induced gastric ulcers
      in rats, evaluating growth factor expression, the angiogenic process, cell
      proliferation and cell apoptosis. Levels of basic fibroblast growth factor (bFGF)
      and vascular endothelial growth factor (VEGF), angiogenesis and cell
      proliferation were analysed by immunohistochemical methods, and apoptosis was
      evaluated by an enzyme immunoassay. Both growth factors and microvessels appeared
      to be abundant in the granulation tissue of the ulcer bed. Rofecoxib (2.5
      mg/kg/day) and ibuprofen (100 mg/kg/day) delayed ulcer healing, but only
      rofecoxib treatment provoked a reduction of bFGF expression and inhibition of the
      development of new microvessels. No changes in VEGF expression were detected.
      Results also showed that proliferation and apoptosis were increased in control
      ulcerated animals. Rofecoxib reduced significantly both processes. These findings
      demonstrate that a reduction of bFGF expression and an antiangiogenic action, as
      well as proliferation/apoptosis inhibition, are some of the mechanisms possibly
      implicated in the delay in ulcer healing seen after the administration of the
      highly selective COX-2 inhibitor rofecoxib.

PMID- 15556153
TI  - Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma,
      protects against gastric ischemia-reperfusion damage in rats: role of oxygen free
      radicals generation.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a nuclear
      hormone receptor super family that has recently been implicated in
      atherosclerosis, inflammation, cancer, infertility, and demyelination. Oxidative
      stress, neutrophil infiltration, proinflammatory cytokines, and the exhibition of
      luminal acid play a role in the pathogenesis of gastric injury induced by
      ischemia-reperfusion. Rosiglitazone, a specific PPAR-gamma ligand, has been shown
      to have antiinflammatory activity, but its effects on experimental ischemia
      reperfusion gastric injury remain unknown. We have investigated the effects of
      the rosiglitazone on gastric injury caused by ischemia following reperfusion in
      rats. Tumour necrosis factor-alpha (TNF-alpha) levels and changes in enzymatic
      activities of myeloperoxidase, as a marker of neutrophils infiltration, xanthine
      oxidase, superoxide dismutase, and glutathione peroxidase, were determined.
      Histological analysis of the lesions was also carried out. Pretreatment with 1 or
      4 mg/kg of rosiglitazone ameliorated the gastric damage induced by clamping the
      celiac artery for 30 min followed by 60 min of reperfusion. It significantly
      (P<0.05) reduced the index of neutrophil infiltration and the levels of the
      cytokine. Rosiglitazone did not revert the reduced glutathione peroxidase
      activity but enhanced significantly (P<0.01) the decreased xanthine oxidase and
      superoxide dismutase activities in gastric mucosa of ischemic rats. In
      conclusion, rosiglitazone reduces the damage in ischemia-reperfusion gastric
      injury and alleviates the inflammatory response and the oxidative events.

PMID- 15556154
TI  - Preventive effect of Y-27632, a selective Rho-kinase inhibitor, on
      ischemia/reperfusion-induced acute renal failure in rats.
AB  - We evaluated the effects of Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)
      cyclohexanecarboxamide dihydrochloride monohydrate], a selective Rho-kinase
      inhibitor, on ischemic acute renal failure. Ischemic acute renal failure in rats
      was induced by clamping the left renal artery and vein for 45 min followed by
      reperfusion, 2 weeks after the contralateral nephrectomy. Y-27632 administration
      (1, 10, and 100 microg/kg, i.p.) before ischemia dose-dependently attenuated the
      ischemia/reperfusion-induced renal dysfunction and histological damage, such as
      tubular necrosis. The ischemia/reperfusion-induced renal dysfunction was also
      overcome by postischemic treatment with Y-27632 at 100 microg/kg, i.p.
      Myeloperoxidase activity in the kidney after ischemia/reperfusion was
      significantly increased, being the maximal level at 6 h after the reperfusion,
      and this increase was also suppressed by Y-27632 (100 microg/kg, i.p.). These
      results indicate that Y-27632 prevents the development of ischemia/reperfusion
      induced acute renal failure, and the effect is related to the suppression of the
      enhanced myeloperoxidase activity in an early phase after reperfusion, thereby
      suggesting that the Rho/Rho-kinase pathway plays a key role in the pathogenesis
      of ischemic acute renal failure.

PMID- 15556155
TI  - Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and
      EP2302) in vitro and in vivo.
AB  - The oxidation of low-density lipoprotein (LDL) is an important event in the
      development of atherosclerosis. In the present study, the antioxidant properties
      of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) were studied.
      Both compounds inhibited dose-dependently the in vitro oxidation of LDL induced
      by copper ions. EP2306 and EP2302 increased significantly the lag phase of the
      oxidation reaction at 0.1 and 10 microM, respectively, whereas they reduced the
      rate of the reaction at 1 and 10 microM, respectively. This inhibitory effect was
      not due to a free radical scavenging or copper-chelating activity of EP2300
      compounds. Moreover, EP2306 and EP2302 inhibited 12-lipoxygenase activity dose
      dependently with IC50 values of 454 and 318 microM, respectively, but had no
      effect on 15-lipoxygenase activity. In hyperlipidaemic rabbits treated with
      EP2306 for 4 weeks, there was a decrease in thiobarbituric acid-reactive
      substance (TBARS) levels and a significant increase in total peroxyl radical
      trapping potential (TRAP) levels as compared to control animals. The present data
      suggest that EP2300 compounds are effective inhibitors of copper-mediated LDL
      oxidation in vitro. Moreover, EP2306 acts as an antioxidant in hyperlipidaemic
      rabbits, a property which could be beneficial in reducing atherosclerosis.

PMID- 15556156
TI  - A novel Syk kinase-selective inhibitor blocks antigen presentation of immune
      complexes in dendritic cells.
AB  - The initiation of antigen presentation by dendritic cells requires proper
      internalization of antigens through various mechanisms. Internalization of immune
      complexes via Fc receptors has been shown to be around 100 times more efficient
      than the internalization of non-complexed antigens. Spleen tyrosine kinase (Syk)
      plays an essential role in the signaling cascade initiated by immunoglobulin
      receptors. We used a selective Syk inhibitor, 7-(3,4-dimethoxyphenyl)-N-1H
      indazol-6-ylimidazo[1,2-c]pyrimidin-5-amine dihydrochloride (compound-D), to
      evaluate the role of Syk in antigen presentation by mouse bone marrow-derived
      dendritic cells. In line with our expectation, compound-D concentration
      dependently inhibited the internalization of immune complexes but not that of
      antigen itself. Furthermore, when dendritic cells were pretreated with compound
      D, the ability of dendritic cells to present immune complex antigens to Th2 cells
      was attenuated, parallel by a reduced release of interleukin-4 production in Th2
      cells. Therefore, Syk kinase activity is a critical component in the process of
      Fcgamma receptor-mediated internalization of immune complex antigens in dendritic
      cells, and Syk kinase inhibitors may be beneficial in selectively suppressing
      antibody-mediated antigen presentation in allergic diseases.

PMID- 15556157
TI  - Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice
      with atopic dermatitis.
AB  - NC/Nga mice have similar pathological and behavioral features of human atopic
      dermatitis and are used as a model of the disease. Under conventional
      circumstances, spontaneous and persistent scratching is frequent and can lead to
      the onset of skin inflammation. We examined the effects of several prostanoids
      and their related compounds on the scratching behavior of NC/Nga mice. Among
      them, topically applied prostaglandin D2, prostaglandin E1, prostaglandin E2 and
      prostaglandin I2 significantly suppressed the scratching, the order of inhibitory
      activities being prostaglandin D2>>prostaglandin I2>prostaglandin
      E1=prostaglandin E2. Prostaglandin D2 metabolite, prostaglandin J2 also
      significantly suppressed the scratching but not so 13,14-dihydro-15-keto
      prostaglandin D2, and 15-deoxy-Delta12,14-prostaglandin J2. The order of the
      inhibitory activities of these prostaglandin D2 metabolites depended on affinity
      of the prostanoid DP1 receptor but not on the DP2 receptor (chemoattractant
      receptor-homologous molecule expressed on T helper2 cells, CRTH2) and PPAR-gamma
      receptors. Likewise, topically applied arachidonic acid significantly suppressed
      the scratching while indomethacin enhanced it. Pretreatment of arachidonic acid
      increased the skin prostaglandins (prostaglandin D2, prostaglandin E2,
      prostaglandin F2alpha and 6-keto-prostaglandin F1alpha) contents, but
      indomethacin decreased the prostaglandin D2 and prostaglandin E2 contents. On the
      other hand, prostaglandin D2 and indomethacin had no apparent effects on
      histamine-induced scratching of ICR mice. These results suggested that
      prostaglandin D2 plays a physiological role in inhibiting pruritus of NC/Nga mice
      via their specific prostanoid DP1 receptors, and that prostaglandin D2 and/or a
      prostanoid DP1 receptor agonist may have therapeutic effects for cases of
      consecutive skin inflammation.

PMID- 15556158
TI  - Involvement of the active metabolites in the inhibitory activity of K579 on rat
      plasma dipeptidyl peptidase IV.
AB  - K579 ((S)-1-[4-methyl-1-(2-pyrimidinyl)-4-piperidylamino]acetyl-2
      pyrrolidinecarbonitrile), which is a long-acting and a slow binding dipeptidyl
      peptidase IV inhibitor, preserved the endogenously secreted active forms of
      glucagon-like peptide-1, augmented the insulin response and ameliorated the
      glucose excursion during oral glucose tolerance test in rats. In this study, we
      measured plasma concentrations of K579 after oral administration to rats.
      However, K579 was eliminated rapidly from plasma after oral administration to
      rats. Therefore, we postulated that there are active metabolites of K579 in rat
      plasma. We investigated the effect of K579 on plasma dipeptidyl peptidase IV
      activity using bile duct-cannulated rats. The duration of inhibitory action of
      plasma dipeptidyl peptidase IV after the administration of K579 in bile duct
      cannulated rats was shorter than that in sham-operated rats. Moreover, we
      investigated the effect of bile obtained from K579-treated rat on plasma
      dipeptidyl peptidase IV activity in normal rats. The bile collected from K579
      treated rats exhibited tardive and potent inhibitory activity of normal rat
      plasma. These results suggest that K579 sustained the duration of inhibitory
      action of plasma dipeptidyl peptidase IV by the character as a slow-binding
      inhibitor and, as well, by the presence of metabolites of K579, which exhibit the
      inhibitory activity of dipeptidyl peptidase IV.

PMID- 15556159
TI  - Altered glucose homeostasis in alpha2A-adrenoceptor knockout mice.
AB  - To elucidate the functions of alpha2-adrenoceptor subtypes in metabolic
      regulation, we determined plasma glucose and insulin levels and tissue uptake of
      the glucose analogue 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in C57Bl/6J wild
      type (WT) and alpha2A-adrenoceptor knockout (alpha2A-KO) mice at baseline and
      following alpha2-adrenoceptor agonist ((+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H
      imidazole (dexmedetomidine)) and antagonist (4-[2-ethyl-2,3-dihydro-1H-inden-2
      yl]-1H-imidazole (atipamezole)) administration. Basal glucose levels were 30%
      lower in alpha2A-KO mice than in WT mice. In WT mice, dexmedetomidine lowered
      insulin and elevated glucose levels, and atipamezole reduced glucose levels. In
      alpha2A-KO mice, neither drug affected the glucose or insulin levels. [18F]FDG
      uptake was investigated in plasma, heart, liver, kidney, pancreas, lung, fat, and
      skeletal muscle. Cardiac [18F]FDG uptake was a sensitive indicator of sympathetic
      function. Liver [18F]FDG uptake conformed to the plasma glucose levels. In
      alpha2A-KO mice, drug effects on [18F]FDG tissue uptake were absent. Thus, the
      alpha2A-adrenoceptor is the alpha2-adrenoceptor subtype primarily involved in the
      regulation of blood glucose homeostasis in vivo.

PMID- 15556160
TI  - Ziprasidone suppresses olanzapine-induced increases in ingestive behaviour in the
      rat.
AB  - Many atypical antipsychotic drugs, such as olanzapine, induce significant weight
      gain. However, ziprasidone produces minimal weight gain, the mechanism of which
      remains unclear. The aim of the present study was to investigate whether
      ziprasidone would reduce the acute effect of olanzapine on feeding behaviour. The
      results suggest that ziprasidone suppresses the significant increases in food
      intake produced by olanzapine, indicating that it has an intrinsic protective
      mechanism against drug-induced increases in food intake.

PMID- 15556161
TI  - From inhibition to excitation: functional effects of interaction between opioid
      receptors.
AB  - Opioids have excitatory effects in multiple regions of the nervous system.
      Excitation by opioids is generally attributed to inhibition of inhibitory
      pathways (disinhibition). However, recent studies indicate that opioids can
      directly excite individual cells. These effects may occur when opioid receptors
      interact with other G protein coupled receptors, when different subtypes of
      opioid receptors interact, or when opioids transactivate other receptors such as
      receptor tyrosine kinases. Changes in the relative level of expression of
      different receptors in an individual cell may therefore determine its functional
      response to a given ligand. This phenomenon could represent an adaptive mechanism
      involved in tolerance, dependence and subsequent withdrawal.

PMID- 15556162
TI  - MAPK pathway mediates the protective effects of onychin on oxidative stress
      induced apoptosis in ECV304 endothelial cells.
AB  - Our recent studies have shown that onychin could protect rabbit aortic rings from
      lysophosphatidylcholine-induced injury by preserving endothelium-dependent
      relaxation and alleviating acute endothelial damage mediated by oxidative stress.
      However, the effect of onychin on apoptosis of endothelial cells induced by
      oxidative stress was not evaluated. In the present study, we investigated the
      effect of onychin on Hydrogen Peroxide (H2O2) induced apoptosis of ECV304
      endothelial cells. Cultured human umbilical vein endothelial cell line (ECV304)
      was pretreated with vehicle (DMSO), genistein, or different concentrations of
      onychin (0.1, 0.3, 1, 3, and 10 micromol/L) for 30 minutes and then exposed to 1
      mmol/L H2O2 for 24 hours. Cell apoptosis was determined by TUNEL and flow
      cytometric analysis. Meanwhile, Western-blot was used to measure the expression
      of phospho-ERK1/2, phospho-p38 and caspase-3. Our data showed that onychin
      treatment exhibited a protective effect on ECV304 endothelial cells from H2O2
      induced apoptosis in a concentration-dependent manner. Moreover, onychin
      attenuated H2O2-induced phosphorylation of p38MAPK and increased H2O2-induced
      phosphorylation of ERK1/2. Furthermore, onychin decreased the activation of
      caspase-3. The opposing effects of onychin on phosphorylation levels of p38MAPK
      and ERK1/2, and its caspase-3 inhibition might play a role in the beneficial
      effect of onychin on endothelial injury.

PMID- 15556163
TI  - Possible involvement of neuronal nitric oxide synthase enzyme in early-phase
      isoflurane-induced hypotension in rats.
AB  - This study was conducted to demonstrate the involvement of nitric oxide synthase
      (NOS) in the early-phase isoflurane-induced hypotension and to ascertain whether
      this NOS is neuronal NOS (nNOS) or endothelial NOS (eNOS). Mean arterial
      pressures (MAPs) were directly measured from the femoral arteries of urethane
      anesthetized rats. Isoflurane-induced changes in MAP were monitored in rats
      following pretreatment with vehicle or one of the following NOS inhibitors: L
      NG)monomethyl-L-arginine (L-NMMA), which is non-selective; L-NG)nitro arginine (L
      NOARG), which is more selective for nNOS and eNOS; and 7-nitroindazole (7-NI),
      which is selective for nNOS. Exposure to 2% isoflurane in oxygen produced a
      triphasic reduction in MAP, including an early phase in which mean arterial
      pressure (MAP) fell by 25-30% during the initial 2(1/2) min. This early
      hypotensive response, but not subsequent phases, was abolished by i.v.
      pretreatment with either L-NMMA or L-NOARG. The early-phase hypotension was also
      significantly attenuated by i.p. pretreatment with 7-NI; however, the blockade
      was not as complete as with L-NMMA or L-NOARG. Cerebella and aorta were removed
      from vehicle- and 7-NI pretreated rats and assayed for NOS activity by
      determining the conversion of [14C]L-arginine to [14C]L-citrulline. The 7-NI
      pretreatment significantly reduced NOS activity in the cerebellum but not the
      aorta. These findings indicate that the early-phase isoflurane-induced
      hypotension may involve nNOS as well as eNOS. The nNOS may participate in
      regulation of isoflurane-induced neuronal release of endogenous opioid peptide,
      which produces a vasodilation that is dependent on NO derived from an action of
      eNOS.

PMID- 15556164
TI  - Effect of beta-alanyl-L-histidinato zinc on the differentiation of C2C12 cells.
AB  - Although beta-alanyl-L-histidinato zinc (AHZ) can promote osteoblast
      differentiation, the molecular mechanism responsible is not fully understood. The
      purpose of this study was to determine the effect of AHZ on undifferentiating
      mesenchymal cells. C2C12, a typical pluripotential mesenchymal cell line, was
      used. The cells were cultured in 5% serum-containing medium to induce
      differentiation, either with or without the addition of AHZ. Cell lineage was
      determined by immunostaining of type II myosin heavy chains, alkaline phosphatase
      (ALPase) activity, mRNA expression of cellular phenotype-specific markers using
      semi-quantitative reverse transcriptase-polymerase chain reaction, and core
      binding factor alpha1/runt-related transcription factor-2 (Cbfa1/Runx2) protein
      synthesis using Western blot analysis. C2C12 cells cultured in the presence of
      AHZ were strongly inhibited from developing into myoblasts, and showed high
      ALPase activity that was approximately double that in the vehicle. The expression
      of mRNA for Cbfa1/Runx2, ALPase, Sox9 and type X collagen was increased markedly
      by the AHZ-stimulated medium, whereas that of desmin and MyoD mRNA was
      drastically decreased. AHZ increased Cbfa1/Runx2 protein expression
      substantially. These results provide clear evidence that AHZ converts the
      differentiation pathway of C2C12 cells to the osteoblast and/or chondroblast
      lineage.

PMID- 15556165
TI  - Platelet serotonin concentration in alcoholic subjects.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is assumed to play a role in the
      pathophysiology of different psychiatric disorders including alcoholism. Since
      platelets and central serotonergic synaptosomes share similar pharmacodynamics of
      5-HT, this study determined platelet 5-HT concentration in 148 male and 42 female
      drug-free subjects with alcohol dependency, according to the DSM-IV criteria, and
      in sex-and age-matched controls. Male and female alcoholics had significantly
      lower platelet 5-HT concentration than 110 male and 123 female healthy controls.
      Sex differences, i.e. higher platelet 5-HT concentration in men than in women,
      were found both in healthy and alcoholic subjects. Platelet 5-HT concentration
      differed significantly in male and female alcoholic subjects with or without
      different psychiatric comorbidities. Platelet 5-HT concentration was higher in
      male alcoholics with comorbid posttraumatic stress disorder (PTSD) than in male
      alcoholics with comorbid anxious-depressive disorder, or depression, or male
      alcoholics without any psychiatric comorbidities. Comorbid depression in female
      alcoholics slightly elevated platelet 5-HT levels but these values were still
      reduced compared to values in healthy women. Smoking status did not affect
      platelet 5-HT concentration either in healthy or in alcoholic subjects. The data
      from our study show sex differences, and reduced platelet 5-HT values, regardless
      of the nicotine dependence, in the large groups of male and female alcoholic
      subjects. Among male alcoholics the presence of comorbid PTSD partly normalized
      the decreased platelet 5-HT values. The results of the present study support the
      hypothesis that alterations in 5-HT system might be related to alcoholism.

PMID- 15556166
TI  - Cholestane-3beta, 5alpha, 6beta-triol promotes vascular smooth muscle cells
      calcification.
AB  - Oxysterols found in atherosclerotic plaque may be associated with vascular
      calcification. We investigated the effect of oxysterol cholestane-3beta, 5alpha,
      6beta-triol (Triol) on in vitro calcification of rat vascular smooth muscle cells
      (VSMCs). In vitro calcification was induced by incubation of VSMCs with beta
      glycerophosphate. Calcifying nodule formation, calcium deposition in
      extracellular matrix, and alkaline phosphatase (ALP) activity were measured as
      indices of calcification. Because apoptotic bodies can serve as nucleation sites
      for calcification, apoptosis of calcifying VSMCs was determined by Hoechst 33258
      staining, TUNEL, and FITC-labeled annexin V/PI double staining. The calcium
      deposition and ALP activity in calcifying VSMCs were much higher than those in
      non-calcifying VSMCs. Triol increased calcifying nodule formation, calcium
      deposition, ALP activity, and apoptosis of nodular cells in calcifying VSMCs. As
      determined by 2,7-dichlorofluorescein fluorescence, Triol induced the generation
      of reactive oxygen species (ROS) in calcifying VSMCs dose- and time-dependently.
      Triol-induced increases in calcium deposition, ALP activity, apoptosis, and ROS
      generation were all attenuated by antioxidant vitamin C plus vitamin E (VC + VE).
      The results demonstrated that Triol promoted VSMCs calcification through direct
      increase of ALP activity and apoptosis, probably by ROS-related mechanism.

PMID- 15556167
TI  - Chilean propolis: antioxidant activity and antiproliferative action in human
      tumor cell lines.
AB  - Propolis, a natural product derived from plant resins collected by honeybees, has
      been used for thousands of years in traditional medicine all over the world. The
      composition of the propolis depends upon the vegetation of the area from where it
      was collected and on the bee species. In this study, we investigated the
      antioxidant activity of a propolis sample, provided by NATURANDES-CHILE,
      collected in a temperate region of central Chile. In addition, this natural
      compound was tested for its antiproliferative capacity on KB (human mouth
      epidermoid carcinoma cells), Caco-2 (colon adenocarcinoma cells) and DU-145
      (androgen-insensitive prostate cancer cells) human tumor cell lines. Results
      showed that this Chilean propolis sample exhibits interesting biological
      properties, correlated with its chemical composition and expressed by its
      capacity to scavenge free radicals and to inhibit tumor cell growth.

PMID- 15556168
TI  - Intermittent high altitude hypoxia protects the heart against lethal Ca2+
      overload injury.
AB  - Adaptation to intermittent high altitude (IHA) hypoxia can protect the heart
      against ischemia-reperfusion injury. In view of the fact that both Ca2+ paradox
      and ischemia-reperfusion injury are associated with the intracellular Ca2+
      overload, we tested the hypothesis that IHA hypoxia may protect hearts against
      Ca2+ paradox-induced lethal injury if its cardioprotection bases on preventing
      the development of intracellular Ca2+ overload. Langendorff-perfused hearts from
      normoxic and IHA hypoxic rats were subjected to Ca2+ paradox (5 min of Ca2+
      depletion followed by 30 min of Ca2+ repletion) and the functional, biochemical
      and pathological changes were investigated. The Ca2+ paradox incapacitated the
      contractility of the normoxic hearts, whereas the IHA hypoxic hearts
      significantly preserved contractile activity. Furthermore, the normoxic hearts
      subjected to Ca2+ paradox exhibited a marked reduction in coronary flow, increase
      in lactate dehydrogenase release, and severe myocyte damage. In contrast, these
      changes were significantly prevented in IHA hypoxic hearts. We, then, tested and
      confirmed our hypothesis that the protective mechanisms are mediated by
      mitochondria ATP-sensitive potassium channels (mitoKATP) and Ca2+/calmodulin
      dependent protein kinase II (CaMKII), as the protective effect of IHA hypoxia was
      abolished by 5-hydroxydecanoate, a selective mitoKATP blocker, and significantly
      attenuated by KN-93, a CaMKII inhibitor. In conclusion, our studies offer for the
      first time that IHA hypoxia confers cardioprotection against the lethal injury of
      Ca2+ paradox and give biochemical evidence for the protective mechanism of IHA
      hypoxia. We propose that researches in this area may lead a preventive regimen
      against myocardial injury associated with Ca2+ overload.

PMID- 15556169
TI  - Regional difference of glutamate-induced swelling in cultured rat brain
      astrocytes.
AB  - L-glutamate (glutamate) is an important neurotoxin as well as the major
      excitatory neurotransmitter. Extracellular glutamate levels are elevated
      following ischemia, hypoglycemia, and trauma. One consequence of elevated
      glutamate levels is cell swelling. Such swelling occurs primarily in astroglial
      cells. We characterized the regional difference in glutamate-induced swelling
      response of cultured astrocytes from rat cerebral cortex, hippocampus and
      cerebellum. Glutamate produced dose-dependent astrocytic swelling in both
      cerebral cortex and hippocampus, showing a maximal effect in 0.5 mM
      concentration, as measured by 3-O-methyl-D-[1-3H]glucose uptake. However, in
      cerebellum, glutamate did not produce astrocytic swelling. It has been suggested
      that Na+ -dependent glutamate uptake is a possible mechanism of glutamate-induced
      swelling. The Vmax for glutamate uptake into cerebellum astrocytes was
      significantly lower (6.7 nmol/mg protein/min) than those for cerebral cortex and
      hippocampus astrocytes (13.0 and 12.0 nmol/mg protein/min, respectively). In
      three regions, more than 90% of the cultured cells showed glial fibrillary acidic
      protein (GFAP) immunoreactivity. Immunoreactivity of GLT, one of the markers of
      glutamate transporters, which is expressed at low levels in cultured astrocytes,
      did not show any differences in three regions. However, immunoreactivities of
      GLAST, the other astroglial glutamate transporter, and aquaporin4 (APQ4), a water
      transporter, were significantly higher in cerebral cortex and hippocampus than in
      cerebellum. These results may explain the regional difference of glutamate
      induced astrocytic swelling.

PMID- 15556170
TI  - Protective effect of Centella asiatica on antioxidant tissue defense system
      against adriamycin induced cardiomyopathy in rats.
AB  - Increased oxidative stress and antioxidant deficit have been suggested to play a
      major role in adriamycin induced cardiomyopathy and congestive heart failure due
      to multiple treatments with adriamycin. In this study the cardio protective
      effect of Centella asiatica on myocardial marker enzymes and antioxidant enzymes
      in adriamycin induced cardiomyopathy was investigated in rats. The rats
      administered with adriamycin (2.5 mg/kg body wt, i.p) caused myocardial damage
      that was manifested by the elevation of serum marker (LDH, CPK, GOT and GPT)
      enzymes and showed significant changes in the antioxidant enzymes (SOD, CAT, GPx,
      GST). Pre-co-treatment with Centella asiatica(200 mg/kg of body wt/oral) extract
      significantly prevented these alterations and restored the enzyme activities to
      near normal levels. These findings demonstrate the cardio protective effect of
      Centella asiatica on antioxidant tissue defense system during adriamycin induced
      cardiac damage in rats.

PMID- 15556171
TI  - Animal rights activists who have targeted for harassment and abuse.

PMID- 15556172
TI  - Applications of C and N stable isotopes to ecological and environmental studies
      in seagrass ecosystems.
AB  - Stable isotopes of carbon and nitrogen are increasingly used in marine
      ecosystems, for ecological and environmental studies. Here, we examine some
      applications of stable isotopes as ecological integrators or tracers in seagrass
      ecosystem studies. We focus on both the use of natural isotope abundance as food
      web integrators or environmental tracers and on the use of stable isotopes as
      experimental tools. As ecosystem integrators, stable isotopes have helped to
      elucidate the general structure of trophic webs in temperate, Mediterranean and
      tropical seagrass ecosystems. As environmental tracers, stable isotopes have
      proven their utility in sewage impact measuring and mapping. However, to make
      such environmental studies more comprehensible, future works on understanding of
      basic reasons for variations of N and C stable isotopes in seagrasses should be
      encouraged. At least, as experimental tracers, stable isotopes allow the study of
      many aspects of N and C cycles at the scale of a plant or at the scale of the
      seagrass ecosystem.

PMID- 15556173
TI  - Investigation of natural and anthropogenic hydrocarbon inputs in sediments using
      geochemical markers. II. Sao Sebastiao, SP--Brazil.
AB  - The Sao Sebastiao Channel, NE Sao Paulo State, Brazil, is an area of
      environmental interest of that state not only because of the tourism, but also
      because of the presence of the most important oil terminal of Brazil, the
      PETROBRAS Maritime Terminal (DTCS). Sediment samples were collected at 15 sites
      in the channel, extracted and analyzed by GC/FID and GC/MS for composition and
      levels of the following organic geochemical markers: aliphatic hydrocarbons
      (normal and isoprenoid alkanes), petroleum biomarkers, linear alkylbenzenes
      (LABs) and polycyclic aromatic hydrocarbons (PAHs). The total concentrations
      varied from 0.04 to 8.53 micorg g(-1) for aliphatics, from 51.1 to 422.0 ng g(-1)
      for petroleum biomarkers, from 12.6 to 27.7 ng g(-1) for LABs and from 20.4 to
      200.3 ng g(-1) for PAHs. The PETROBRAS Maritime Terminal (DTCS), Sao Sebastiao
      Harbor and sewage outfalls along the area had clear influences on the geochemical
      marker concentrations, especially at locales in the central and north parts of
      the channel.

PMID- 15556174
TI  - Avoidance of crude-oil contaminated sediment by the Australian seastar,
      Patiriella exigua (Echinodermata: Asteroidea).
AB  - This study attempted to determine whether Patiriella exigua, an Australian
      seastar, could detect and/or avoid oiled sediment when given an equal choice of
      unoiled sediment. The sediment was spiked once to produce one of three
      concentrations of oiled sediment used in the test chambers versus unoiled
      sediment. Behavioral observations were repeated over a 32 day period to test the
      effects of aging the oiled sediment. Results show that Patiriella exigua was
      capable of detecting oiled sediment and/or an oiled environment. Seastars avoided
      oiled sediment, with significantly higher numbers choosing either to reside on
      the clean sediment (p<0.05) or to travel up the glass sides of the tanks
      (p<0.001). Avoidance of oiled sediment increased with increasing sediment oil
      concentrations. Aging the oiled sediment decreased the oil content of the
      sediment and increased the number of seastars able to inhabit it (p<0.001). A
      potential narcotic effect of exposure to oiled sediment was observed.

PMID- 15556175
TI  - A preliminary study of heavy metal contamination in Yangtze River intertidal zone
      due to urbanization.
AB  - Three short sediment cores (<20 cm) were collected in the high, middle and low
      tidal flats in the Yangtze River Estuary near the Southern (Nanqu) Sewage Outlet,
      one of the three largest sewage outlets in Shanghai, China. All samples were
      analyzed for Al, Cu, Pb, Zn, 210Pb and 7Be. The 210Pbxs profile shows a non
      steady-state sedimentation pattern in the study area and 7Be is only found in the
      upper 1 cm layer of sediment in high and middle tidal flats. In this study, we
      found that Cu, Pb and Zn contaminants are present in the upper 20 cm of the tidal
      flat sediment and, after normalizing with Al, the contamination is more striking
      in the upper approximately 5 cm sediment. Relationships between the metal (Cu, Pb
      and Zn) enrichment factor and 210Pbxs activity suggest that contamination
      increases with time. Factor analyses shows that differences in sediment grain
      size have insignificant effects on Cu and Pb concentrations, but have some
      influence on Zn concentration in the study area. This preliminary study shows
      that urbanization and recent coastal wetland reclamation have had an
      environmental impact on this area.

PMID- 15556176
TI  - Use of a by-product of peat excavation, cotton grass fibre, as a sorbent for oil
      spills.
AB  - The sorbents used to collect oil in case of oil-spills are mostly synthetic,
      which limits the possibilities of their disposal. We studied the absorption
      capacities and rates of cotton grass fibre, a by-product of peat excavation, and
      cotton grass mats for several oil types and compared them with a synthetic,
      commercially available oil sorbent. We found cotton grass fibre to have superior
      absorption properties: Cotton grass sorbent absorbed oil approximately two to
      three times as much, and two to three times as fast as the synthetic one. Cotton
      grass fibre absorbed no measurable amount of water in the conditions used in the
      tests making it ideal for absorbing oil from the surface of water. In removing
      diesel oil from the surface of water, the efficiency was over 99% up to an
      absorbing factor of 20 times its own weight. The biodegradable cotton grass fibre
      proved to be an effective oil sorbent with low raw-material costs.

PMID- 15556177
TI  - Residues of selected antibiotics in water and mud from shrimp ponds in mangrove
      areas in Viet Nam.
AB  - In recent years, antibiotics have been used widely in intensive shrimp culture
      and this may lead to their contamination of the environment. Surveys on residues
      of trimethoprim (TMP), sulfamethoxazole (SMX), norfloxacin (NFXC) and oxolinic
      acid (OXLA) in water and mud in shrimp ponds in mangrove areas were conducted in
      the north as well as in south of Viet Nam in July and August, 2002. The results
      show that these antibiotics are found in all samples in both shrimp ponds and
      surrounding canals. The highest concentrations of TMP, SMX, NFXC and OXLA are
      1.04, 2.39, 6.06, and 2.50 ppm in water samples; and 734.61, 820.49, 2615.96,
      426.31 ppm (based on wet mud weight), respectively. The comparison of antibiotics
      residues between study sites and types of shrimp ponds will be discussed in this
      paper. The results also suggest that antibiotics residues may cause harmful
      effect on ecosystems in the study sites.

PMID- 15556178
TI  - The distribution and inventory of total and methyl mercury in Kuwait Bay.
AB  - Sediment (surface and core) sampling was conducted during the period from August
      96-December 98 from intertidal and offshore areas in Kuwait Bay. The highest (and
      most variable) concentrations of total mercury (T-Hg; 36500+/-34930 ng g(-1)) are
      encountered around the previous industrial outfall where sediments are disturbed
      by shipping activities. The concentrations of T-Hg are lower in the Shuwaikh Port
      area (650+/-210 ng g(-1)) and continue to decrease towards the northern coastline
      of Kuwait Bay (average concentrations in the wider Bay region are 50+/-30 ng g(
      1)). These values are still above background concentrations of 15-20 ng g(-1).
      Calculation of the total inventory of mercury in all the surface sediments of the
      studied area indicates that approximately 22.5 ton is present which is similar to
      the estimated industrial discharges of approximately 20 ton suggesting that the
      contamination is largely confined to the Bay and that releases to the wider Gulf
      region are small. The distributions of MeHg are similar to those of T-Hg and
      represent ranges between 0.23% and 0.5% of the T-Hg indicating that surface
      sediments within Kuwait Bay contain approximately 80 kg of this chemical.

PMID- 15556179
TI  - Organochlorine compounds in tissues of swordfish (Xiphias gladius) from
      Mediterranean Sea and Azores islands.
AB  - Polychlorobiphenyls (PCB) and organochlorine (OC) pesticides are endocrine
      disrupting chemicals (EDCs). The Italian Ministry of Environment has undertaken a
      program (1999-2001) to measure levels of contaminants in top marine predators and
      to develop sensitive biomarkers for the evaluation of toxicological risk in these
      species. In 1999, 15 swordfishes (Xiphias gladius) taken from the Mediterranean
      Sea along the Sicilian coast (Strait of Messina, Italy) and in the Atlantic Ocean
      along the Azores Islands, and analysed for 34 congeners of PCBs and 27
      organochlorine (OC) pesticides in gonad, muscle, liver and blubber tissues. In
      the tissues of Mediterranean swordfishes the sum of the determined PCBs congeners
      ranged from 4.61 to 4651.17 ng g(-1) on fresh tissue basis. Among organochlorine
      pesticides DDE, DDT and DDD (TDE) predominated with an overall range of 2.37
      4734.56 ng(-1) w.w. In particular p,p'-DDE had concentrations appearing up to
      3900 ng(-1), with the highest values found in fatty tissues, such as blubber. In
      the liver of Azores Island swordfishes lower levels of summation PCBs (8.43
      294.17 ng/g w.w.) and summation DDTs (<0.01-217.44 ng/g w.w.) were determined.

PMID- 15556180
TI  - Bacteriological indicators of anthropogenic impact prior to and during the
      recovery of water quality in an extremely polluted estuary, Golden Horn, Turkey.
AB  - Five years of monthly data of indicator bacteria from 1998 to 2002 were evaluated
      to find out the changes in water quality during the rehabilitation of the Golden
      Horn, an estuary severely polluted from industrial and domestic discharges since
      the 1950s. Surface fecal coliform was above 10(6) CFU/100 ml at the inner part in
      1998. Following the achievement of healthy water circulation and control of most
      surface discharges, fecal coliform and fecal streptococci counts decreased below
      10(3) CFU/100 ml in the summer of 2002. However, the decrease was interrupted by
      sudden shifts in rainy periods. Runoff, enhanced by domestic inputs during
      rainfall, has become the main factor influencing water quality in the estuary
      today. Increasing values of fecal coliform were observed during periods of low
      salinity, pH, dissolved oxygen and high ortho-phosphate, whilst decreasing values
      were detected during high salinity, pH and dissolved oxygen and low ortho
      phosphate periods. Striking changes were observed within five years, promising
      that even an anoxic water body can turn into a recreational area with appropriate
      treatment.

PMID- 15556181
TI  - Effects of oil spill on seawater infiltration and macrobenthic community in tidal
      flats.
AB  - Tidal flat ecosystem simulators are used to clarify the effects of stranded fuel
      oil on tidal flat ecosystems. Results show that oil spills increase the
      periphyton on sediment by decreasing the predation stress caused by deposit
      feeders. About a month after an oil spill, the total population density of the
      macrobenthos recovered. The oxidation-reduction potential in the surface sediment
      drops to a negative value after the oil spill, and the anaerobic condition
      throughout the sediment seems to be responsible for the decrease in the
      population density of the macrobenthos. The infiltration volume of seawater into
      the oil-stranded sediment decreases to a third of that without the oil spill. The
      recovery of infiltration volume after about a month coincides with the recovery
      of the population density of the macrobenthos. This result suggests that the
      macrobenthic population is highly dependent on the infiltration of seawater.

PMID- 15556182
TI  - A direction-sensitive underwater blast detector and its application for managing
      blast fishing.
AB  - Little is known about the spatial and temporal distribution of blast fishing
      which hampers enforcement against this activity. We have demonstrated that a
      triangular array of hydrophones 1 m apart is capable of detecting blast events
      whilst effectively rejecting other sources of underwater noise such as snapping
      shrimp and nearby boat propellers. A total of 13 blasts were recorded in Sepangor
      bay, North of Kota Kinabalu, Sabah, Malaysia from 7th to 15th July 2002 at
      distances estimated to be up to 20 km, with a directional uncertainty of 0.2
      degrees . With such precision, a network of similar hydrophone arrays has
      potential to locate individual blast events by triangulation to within 30 m at a
      range of 10 km.

PMID- 15556183
TI  - Accumulation of hexavalent chromium by an exopolysaccharide producing marine
      Enterobacter cloaceae.
AB  - An exopolysaccharide producing Enterobacter cloaceae (AK-I-MB-71a) was tested for
      its Cr (VI) tolerance. This isolate was not only resistant to this heavy metal
      but also showed enhanced growth and exopolysaccharide production in the presence
      of Cr (VI) at 25, 50 and 100 ppm concentrations. XRF analysis of both the biomass
      as well as the exopolysaccharide revealed that a sum total of about 60-70%
      chromium was accumulated by this bacterium. This indicated that this organism
      could prove to be a potential candidate in the field of bioremediation with
      respect to chromium removal.

PMID- 15556184
TI  - Allozyme genotypes and tolerance to copper stress in Hediste diversicolor
      (Polychaeta: Nereididae).
AB  - This study analysed the occurrence of genotypic shifts in laboratory populations
      of Hediste diversicolor (Polychaeta: Nereididae) exposed to copper stress.
      Specimens of H. diversicolor were collected at three sites, up to 10 km apart, in
      the estuarine area of the Pialassa lagoons (North Adriatic Sea, Italy) and were
      used in acute toxicity tests. Specimens were assigned to copper exposure (0.34
      mg/l Cu2+) or control conditions. Each combination of Treatment and Site was
      replicated in two tanks containing 35 specimens of H. diversicolor. The genotypic
      structure of both dead and survived specimens was analysed by allozyme
      electrophoresis at six loci (ALD, FH, HBDH LDH, PGI, SDH). Under copper exposure,
      specimens with the genotypes ALD100/100 and PGI102/102 had significantly lower
      mortalities than other genotypes Results were consistent across the three sites,
      suggesting that, under laboratory conditions, effects of copper stress on H.
      diversicolor is related to individual genotypes at ALD and PGI loci.

PMID- 15556185
TI  - Present state and historical changes of trace metal pollution in Kaoping coastal
      sediments, southwestern Taiwan.
AB  - Surface and gravity-cored sediments were collected from the Kaoping coastal area
      off southwestern Taiwan to determine particle size, organic carbon, trace metal
      concentration and enrichment factor (EF), 210Pb dating, and 206Pb/207Pb ratio for
      determining present and historical metal pollution. Surface distributions of
      trace metals ranged from 0.02 to 0.13 mg/kg for Cd (EF: 0.16-1.65), from 35 to
      189 mg/kg for Cr (EF: 0.85-2.92), from 25 to 64 mg/kg for Ni (EF: 0.53-2.38),
      from 10 to 32 mg/kg for Pb (EF: 1.20-4.94), and from 29 to 129 mg/kg for Zn (EF:
      1.18-3.50). Trace metal concentrations correlate closely with distributions of
      mud (<63 microm) and organic carbon which accumulate largely around river mouths
      and within the Kaoping Canyon. With the exception of Cd, Cr and Ni in certain
      areas with rather coarse sediments, metals were generally elevated above the
      baseline levels over the studied area. Metals were also relatively enriched in
      areas with high contents of mud and organic carbon. Sedimentation rates derived
      from the excess 210Pb data in core sediments sampled from the canyon illustrate
      metal pollution beginning around 1970 that is corresponding to the booming time
      of economic growth in Taiwan. Meanwhile, the status of Pb pollution in core
      sediments is verified by an inversed correlation between 206Pb/207Pb ratios and
      Pb concentrations. Anthropogenic Pb and other metals in the studied area were
      apparently derived primarily from the Kaoping River and accumulated around the
      river mouth and within the Kaoping Canyon. The Kaoping Canyon appears to act as a
      major sink for river borne trace metals.

PMID- 15556186
TI  - Management of exogenous threats to Antarctica and the sub-Antarctic Islands:
      balancing risks from TBT and non-indigenous marine organisms.
AB  - The discovery of high levels of tributyltin compounds in Antarctic marine
      sediments has prompted managers to consider the banning of such substances in
      this region. We propose that the banning of antifouling coatings may result in an
      increase in the risk of non-indigenous species invasions. Our studies show that
      un-treated vessels carry a more diverse community of fouling organisms than
      treated hulls on which fouling is restricted to specific untreated niches. Up to
      40% of the species recruited to the hulls of Southern Ocean vessels are species
      with invasive histories. Viable fouling assemblages can survive prolonged voyages
      to high-latitude coastlines, yet passage through sea-ice may remove fouling
      communities due to mechanical abrasion reducing the hazard of introductions to
      ice-bound coastlines. The banning of antifouling compounds may be of particular
      concern for the ice-free sub-Antarctic islands which represent a common anchorage
      point for vessels on-route to Antarctica.

PMID- 15556187
TI  - A biological oil adsorption filter.
AB  - A new oil adsorption method called adsorption filtration (AF) has been developed.
      It is a technology where by oil residues can be cleaned from water by running it
      through a simple filter made from freeze treated, dried, milled and then
      fragmented plant material. By choosing suitable plants and fragmentation sizes it
      is possible to produce filters, which pass water but adsorb oil. The aim of this
      study was to investigate the possibilities of manufacturing oil adsorbing filter
      materials from reed canary grass (Phalaris arundinacea), flax (Linum
      usitatissimum L.) or hemp fibre (Cannabis sativa L.). The oil (80 ml) was mixed
      with de-ionised water (200 ml) and this mixture was filtered through 10 or 20 g
      adsorption filters. Fine spring harvested hemp fibre (diameter less than 1 mm)
      and reed canary grass fragments adsorb 2-4 g of oil per gram of adsorption
      material compared to 1-3 g of water. Adsorption filtration is thus a novel way of
      gathering spilled oil in shallow coastal waters before the oil reaches the shore.

PMID- 15556188
TI  - Coastal pollution hazards in southern California observed by SAR imagery:
      stormwater plumes, wastewater plumes, and natural hydrocarbon seeps.
AB  - Stormwater runoff plumes, municipal wastewater plumes, and natural hydrocarbon
      seeps are important pollution hazards for the heavily populated Southern
      California Bight (SCB). Due to their small size, dynamic and episodic nature,
      these hazards are difficult to sample adequately using traditional in situ
      oceanographic methods. Complex coastal circulation and persistent cloud cover can
      further complicate detection and monitoring of these hazards. We use imagery from
      space-borne synthetic aperture radar (SAR), complemented by field measurements,
      to examine these hazards in the SCB. The hazards are detectable in SAR imagery
      because they deposit surfactants on the sea surface, smoothing capillary and
      small gravity waves to produce areas of reduced backscatter compared with the
      surrounding ocean. We suggest that high-resolution SAR, which obtains useful data
      regardless of darkness or cloud cover, could be an important observational tool
      for assessment and monitoring of coastal marine pollution hazards in the SCB and
      other urbanized coastal regions.

PMID- 15556189
TI  - Studies of a contaminated brackish marsh in the Hackensack Meadowlands of
      Northeastern New Jersey: benthic communities and metal contamination.
AB  - Cores taken from 16 stations within Eight Day Swamp, a highly contaminated marsh
      in the Hackensack Meadowlands, were analyzed for metal concentrations and for
      benthic community structure. Metal levels were compared with the benchmark ERM
      values, and expressed in terms of toxic units. Mercury was the most important
      metal in all the samples in terms of its contribution to the total toxic units.
      The overall abundance and taxa richness in the benthic community were associated
      with the height of the location relative to the tidal cycle, but were generally
      not significantly correlated with metal concentrations at the sites. Ordination
      of the communities showed that the communities that were low-lying (on the
      mudflat) were most similar to one another, and those that were higher up on the
      marsh were most similar to one another. However, diversity indices (Shannon
      Wiener H' and Simpson's) were significantly associated with concentrations of the
      metals (except As) and with the sum of the toxic units at a station.

PMID- 15556190
TI  - Variation of phytoplankton biomass and primary production in Daya Bay during
      spring and summer.
AB  - Environmental factors, phytoplankton biomass (Chl a) and primary production of
      two water areas in Daya Bay (Dapeng'ao Bay and Aotou Bay) were investigated
      during the transition period from spring to summer. Chl a ranged from 3.20 to
      13.62 and 13.43 to 26.49 mg m(-3) in Dapeng'ao Bay and Aotou Bay respectively, if
      data obtained during red tides are excluded. Primary production varied between
      239.7 and 1001.4 mg Cm(-2) d(-1) in Dapeng'ao Bay. The regional distribution of
      Chl a and primary production were mostly consistent from spring to summer in both
      bays. Seasonal transition characters have been found in Daya Bay from spring to
      summer, including high values of DO, nitrate and silicate. Size structures of
      phytoplankton and its primary production do not change very much from spring to
      summer, with micro-phytoplankton dominating and contributing about 50% of the
      whole. In Daya Bay, phytoplankton is limited by nitrogen in spring, and by
      phosphate in summer. Artificial impacts are evident from high temperature
      effluent from nuclear power stations, aquaculture and sewage. During the
      investigation, a red tide occurred in Aotou Bay, with a maximum Chl a of 103.23
      mgm(-3) at surface and primary production of 2721.9 mg Cm(-2) d(-1) in the red
      tide center. Raised water temperature and nutrient supply from land-sources help
      to stimulate annual red tides.

PMID- 15556191
TI  - Origin of the anomalies in light and middle REE in sediments of an estuary
      affected by phosphogypsum wastes (south-western Spain).
AB  - Sc, Y, Th, Cu and rare earth elements (REE) concentrations have been analyzed in
      14 samples of surface sediments and in two gravity cores by means of ICP-MS. Mean
      concentrations of Sc, Y and Th in surface sediments are 6.23, 4.76 and 16.30 ppm,
      respectively, lower than those present in the Upper Continental Crust (UCC). Cu
      concentration in these sediments is very high, 1466 ppm, and is caused by inputs
      from the Odiel and Tinto rivers, affected by acid mine drainage. SigmaREE mean
      concentration is 106.8 ppm, lower than that observed in other rivers and
      estuaries. In the cores, Sc, Y and Th concentrations show a significant increase
      in the intermediate levels, between 10 and 40 cm depth. The same pattern exists
      with Cu, where concentrations of 4440 ppm can be reached. Vertical evolution
      patterns for Sc, Y, Cu and heavy REE (HREE) are similar, and contrary to those
      shown by Th, light REE (LREE) and middle REE (MREE). Plots of North American
      Shale Composite (NASC)-normalized REE data of surface sediments show a slight
      depletion in REE concentrations. Most samples present with middle REE enrichment
      relative to light REE and heavy REE. Conversely, samples of the intermediate
      levels of the cores show significant enrichment of REE relative to NASC and high
      values in the (La/Gd)NASC and (La/Yb)NASC ratios. These anomalies in the
      fractionation patterns caused by enrichments in LREE and MREE concentrations is
      related to the presence of high concentrations of Th. They were generated by
      effluents from fertilizer factories between 1968 and 1998 which used phosphorite
      as source material.

PMID- 15556192
TI  - Polycyclic aromatic hydrocarbon contamination and recovery characteristics in
      some organisms after the Nakhodka oil spill.
AB  - Following the oil spill from the Russian tanker Nakhodka in 1997 in the Sea of
      Japan, polycyclic aromatic hydrocarbons (PAH) were monitored for three years in
      some molluscs from the Mikuni-cho shore in Japan. Total PAH concentrations in
      marine organisms except for spiny top shell, ranged from 5.3 to 32.7 ng/g wet
      weight, but no trends were evident. Total PAH concentration in spiny top shell
      (Turbo cornutus) was 44 ng/g w.w. in the first month after the oil spill.
      However, it rapidly decreased to less than 5.4 ng/g w.w. from the second month.
      Spiny top shell, which was exposed to dietary Nakhodka heavy fuel oil,
      concentrated benzo(a)pyrene to 17.1 ng/g w.w. after two weeks of exposure and
      then rapidly eliminated it during an elimination phase. These results suggest
      that spiny top shell accumulates PAHs because of their low ability to metabolize
      PAH, but it can excrete parent PAHs rapidly when removed from the source of
      contamination. Thus it is suitable as an indicator organism in monitoring oil
      contamination. It can also be inferred from these field and laboratory
      investigations that, in three years, organisms from the Mikuni-cho shore seem to
      have adequately recovered from the Nakhodka oil spill contamination.

PMID- 15556193
TI  - Comparison of the acid-base responses to CO2 and acidification in Japanese
      flounder (Paralichthys olivaceus).
AB  - To investigate whether the biological toxicity of aquatic hypercapnia is due to
      the direct effects of CO2 or to the effects of acidification of seawater by CO2,
      the Japanese flounder (Paralichthys olivaceus) was subjected to seawater
      equilibrated with a gas mixture of air containing 5% CO2 (pH 6.18) or seawater
      acidified to the same pH with 1 N H2SO4. All the fish died within 72 h in the CO2
      exposure group, whereas no mortality occurred in the acid group. Acid-base
      parameters as well as plasma ion concentrations were severely perturbed in the
      CO2 exposure group, whereas they were minimally affected in the acid group. These
      results clearly demonstrate that the mortality in the CO2 group is a direct
      result of the elevated levels of dissolved CO2 and not to the effects of the
      reduced water pH.

PMID- 15556194
TI  - Evidence of chromosomal damage in common eiders (Somateria mollissima) from the
      Baltic Sea.
AB  - Common eiders nesting in the Baltic Sea are exposed to generally high levels of
      contaminants including potentially genotoxic polycyclic aromatic hydrocarbons and
      organochlorines. Blood samples were collected from eiders at eight sites in the
      Baltic Sea and two sites in the Beaufort Sea. DNA content variation was estimated
      using the flow cytometric method, and subsequently utilized as a biomarker of
      genetic damage. We observed no significant differences in genetic damage among
      populations within either the Baltic or Beaufort Seas. However, eider populations
      from the Baltic Sea had significantly elevated estimates of genetic damage
      compared to populations from the Beaufort Sea.

PMID- 15556195
TI  - Occurrence and transport of Irgarol 1051 and its major metabolite in coastal
      waters from South Florida.
AB  - Irgarol 1051, a boosting antifouling agent often used to supplement copper based
      paints was found in surface waters from South Florida at stations collected from
      the Miami River, Biscayne Bay and selected areas of the Florida Keys.
      Concentrations of the herbicide ranged from below the method detection limit (1
      ng/L) to as high as 182 ng/L in a canal system in Key Largo. The herbicide was
      present at 93% of the stations and often found in conjunction with its
      descyclopropyl metabolite (M1) previously reported to be the major degradation
      product of Irgarol under natural environmental conditions. The 90th percentile
      concentration calculated for all South Florida samples was 57.6 ng/L. Based on
      available data on the toxicity of Irgarol to algae and coral, only two stations
      (approximately 3%) ranked above the LC50 of 136 ng/L reported for the marine
      algae Naviculla pelliculosa and above the 100 ng/L level reported to reversibly
      inhibit photosynthesis of intact corals. However, a basic dissipation model for
      Irgarol using the Key Largo Harbor station as a point source indicated that
      concentrations of the herbicide decreased rapidly and concentrations below the
      MDL are observed within 2000 m of the source. No major coral based benthic
      habitats are documented for all the stations surveyed at distances that Irgarol
      may pose a substantial risk. However, other types of submerged vegetation like
      seagrasses are common around the marinas and the effects of Irgarol to such
      endpoints should be investigated further.

PMID- 15556196
TI  - An assessment of the pollutant status of surficial sediment in Cork Harbour in
      the South East of Ireland with particular reference to polycyclic aromatic
      hydrocarbons.
AB  - Surface sediment from three polluted sites within Cork Harbour, Ireland, and from
      a relatively clean reference site were collected and analysed for polycyclic
      aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine
      pesticides (OCPs), brominated flame retardants (BFRs), organotins (OTs), and
      heavy metals. PAHs were determined to be the most abundant class of contaminant.
      Concentrations of the sum (Sigma) of the 21 PAHs measured from the Harbour sites
      (2877.70 ng g(-1), 1000.7 ng g(-1) and 924.40 ng g(-1) dry weight respectively)
      were significantly higher than that of the sediment from the reference site
      (528.30 ng g(-1) dry weight). An inner harbour site, Douglas being the more
      contaminated of the three harbour sites. A similar pattern was observed with the
      other contaminants however, these compounds, with the exception of the heavy
      metals, all tended to be detected at concentrations on or below detection limits.

PMID- 15556197
TI  - Anthropogenic iodine-129 in seawater along a transect from the Norwegian coastal
      current to the North Pole.
AB  - Variation in the concentrations of iodine-129 (129I, T1/2=15.7 Myr), a low-level
      radioactive component of nuclear fuel waste, is documented in surface waters and
      depth profiles collected during 2001 along a transect from the Norwegian Coastal
      Current to the North Pole. The surface waters near the Norwegian coast are found
      to have 20 times higher 129I concentration than the surface waters of the Arctic
      Ocean. The depth profiles of 129I taken in the Arctic Ocean reveal a sharp
      decline in the concentration to a depth of about 300-500 m followed by a weaker
      gradient extending down to the bottom. A twofold increase in the 129I
      concentration is observed in the upper 1000 m since 1996. Based on known
      estimates of marine transient time from the release sources (the nuclear
      reprocessing facilities at La Hague, France, and Sellafield, UK), a doubling in
      the 129I inventory of the top 1000 m of the Arctic Ocean is expected to occur
      between the years 2001 and 2006. As 129I of polar mixed layer and Atlantic layer
      of the Arctic Ocean is ventilated by the East Greenland Current into the Nordic
      Seas and North Atlantic Ocean, further dispersal and increase of the isotope
      concentration in these regions will be encountered in the near future.

PMID- 15556198
TI  - Environmental impact of the MV CITA on the foreshore of Porth Hellick, Isles of
      Scilly.
AB  - The grounding of the container feeder vessel MV CITA on Newfoundland Rocks, Isles
      of Scilly, had an effect on the surrounding biota and benthic environment.
      Included in the CITA's cargo were five 40 ft containers holding pallets of
      polyester film used in the production of audio and visual recording tapes. The
      wreckage presented a minor but potentially chronic source of pollution through
      the delayed release of polythene film, which was left on the seabed as it was
      considered insufficiently valuable to warrant salvage. The polythene
      disintegrated and was washed upon the foreshore of Porth Hellick in minute
      shreds. The adjacent foreshore and two control sites within the islands were
      analysed using a 5-strand line and vegetation survey with 10 random quadrats
      within each line to determine the environmental impact of the polythene.

PMID- 15556199
TI  - Accumulation of heavy metals by flounder, Platichthys flesus (Linnaeus 1758), in
      a heterogeneously contaminated nursery area.

PMID- 15556200
TI  - Metal concentrations in macroalgae from East Antarctica.

PMID- 15556201
TI  - Hydrocarbon contamination in mussels from Guanabara Bay.

PMID- 15556202
TI  - Intersex in Roe's abalone (Haliotis roei) in Western Australia.

PMID- 15556203
TI  - Marine environment protection for the North and Baltic Seas.

PMID- 15556204
TI  - Model for oxygen transfer in rotating biological contactor.
AB  - Rotating biological contactor is being widely used for wastewater treatment but
      there is an apparent lack of knowledge about the rate at which oxygen transfer
      occurs, in physical and biological system. In this study the transfer of oxygen
      from air to water by a rotating disc air-liquid contactor in physical system is
      investigated. The oxygen transfer model suggested by Kim and Molof, Water Sci.
      Technol. 14 (1982) 569, was modified and the developed model is termed as
      modified Kim and Molof model. The model was calibrated by using available data in
      literature and validated by experiments conducted in this study. The effect of
      significant physical parameters was integrated into a single term and is termed
      as volume renewal number. The modified Kim and Molof model was compared with the
      other available models. The coefficient of determination (R(2)) for the modified
      Kim and Molof model obtained is 0.95 which is much higher than in the other
      available models. Thereby the model is expected to estimate oxygen transfer more
      accurately. Further, a simplified linear model between K(L)a and the volume
      renewal number is proposed. Both modified Kim and Molof and linear model estimate
      the overall oxygen transfer coefficient (K(L)a) accurately.

PMID- 15556205
TI  - Comparison of the ion exchange uptake of ammonium ion onto New Zealand
      clinoptilolite and mordenite.
AB  - In this study the uptake performances of the naturally occurring zeolite,
      clinoptilolite, and of New Zealand mordenite are compared. The uptake of fully
      ionised ammonium ion from aqueous solutions in the concentration range 0-200 mg/l
      on to these two materials was compared. The influence of other cations present in
      water upon the ammonia uptake was also determined. The cations studied were
      potassium, calcium and magnesium. In all cases the anionic counterion present was
      chloride. The results showed that the mordenite exhibited higher overall uptake
      concentrations at equilibrium compared with clinoptilolite at solution
      concentrations greater than 80 mg/l. Beyond this value, the difference in solid
      phase equilibrium concentrations on the mordenite became greater at higher
      solution-phase ammonium ion concentrations. The effect of the other cations upon
      uptake of ammonium ion was relatively small. In all cases, the ammonium ion
      showed the highest uptake on to both the mordenite and the clinoptilolite. In the
      case of clinoptilolite this was rather an unexpected result since the majority of
      other work shows clinoptilolite exhibiting a higher affinity for potassium ion
      compared with ammonium ion. This may be explained by the fact that the
      clinoptilolite came from volcanic deposits in New Zealand. This is the first such
      study on this material. At solution-phase equilibrium concentrations of greater
      than 80 mg/l, the mordenite showed smaller reductions in ammonium ion uptake in
      the presence of the other cations when compared with clinoptilolite.

PMID- 15556206
TI  - Bioremediation of crystal violet using air bubble bioreactor packed with
      Pseudomonas aeruginosa.
AB  - Seven water and sediment samples were collected and tested for decolorizing
      crystal violet. Pseudomonas aeruginosa was the most effective isolate for dye
      decolorization. The LC(50) of the crystal violet (115 mg/l) was measured using
      Artemia salina as a biomarker. The effect of different heavy metals on crystal
      violet decolorization was investigated. Cd(2+) and Fe(3+) ions showed marginal
      enhancement of the decolorization process, the rate was 1.35 mg/l/h compared to
      1.25 mg/l/h for the control. Phenol and m-cresol showed no effect on crystal
      violet decolorization, meanwhile p-cresol and p-nitrophenol reduced the
      decolorization rate to 1.07 and 0.01 mg/l/h, respectively. P. aeruginosa cells
      were immobilized by entrapment in agar-alginate beads. The beads were cultivated
      and reused in Erlenmeyer flask and in an air bubble column bioreactor and they
      enhanced the crystal violet decolorization rate to 3.33 and 7.5 mg/l/h,
      respectively.

PMID- 15556207
TI  - Development of enzyme-linked immunosorbent assay for detection of alkylphenol
      polyethoxylates and their biodegradation products.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the quantitative
      analysis of alkylphenol polyethoxylates (APnEOs) and their biodegradation
      products. To generate a specific monoclonal antibody (mAb) for the ELISA,
      hybridoma cells were produced by the fusion of mouse myeloma cells and spleen
      cells from mice immunized with nonylphenol polyethoxylate (NPnEO) derivatives
      coupled to bovine serum albumin. The developed ELISA showed the detection limits
      of 16 and 30 microg/L NP10EO when 10% and 60% (v/v) methanol solutions were used
      as assay diluent. The mAb was shown to be specific to APnEOs and their
      metabolites, such as short-ethoxy-chain APnEOs and alkylphenoxy carboxylic acids,
      except for nonylphenol. Moreover, no response was observed with non-APnEO
      surfactants as well as other compounds structurally similar to APnEOs. The
      percentage river water recoveries of 85-118% were obtained for 10 microg/L NP10EO
      fortification after preconcentration by C18 solid-phase extraction. The ELISA was
      also validated by comparing it with high-performance liquid chromatography for
      the analysis of APnEOs and their metabolites in river samples; the correlation
      coefficient between the values obtained by these assays was 0.96.

PMID- 15556208
TI  - Potentials of biological oxidation processes for the treatment of spent sulfidic
      caustics containing thiols.
AB  - This research focused on the biological treatment of sulfidic spent caustics from
      refineries, which contain mainly hydrogen sulfide, methanethiol (MT) and
      ethanethiol (ET). Also various organic compounds can be present such as BTEX.
      Biological oxidation of 2.5 mM MT in batch experiments occurred after MT was
      first auto-oxidized into dimethyldisulfide (DMDS) whereafter oxidation into
      sulfate was completed in 350 h. DMDS as sole substrate was completely oxidized
      within 40 h. Therefore, DMDS formation seems to play an important role in
      detoxification of MT. Biological oxidation of ET and buthanethiol was not
      successful in batch experiments. Complete oxidation of MT and ET was observed in
      flow-through reactor experiments. Simultaneous oxidation of sulfide and MT was
      achieved when treating a synthetic spent caustic, containing 10 mM sulfide and
      2.5 mM MT, in a bubble column reactor with carrier material at a hydraulic
      retention time of 6 h. Addition of 7.5 mM phenol, a common pollutant of spent
      caustics, did not adversely affect the biological oxidation process and phenol
      was completely removed from the effluent. Finally, three different spent caustics
      solutions from refineries were successfully treated.

PMID- 15556209
TI  - Influence of inter-annual variations in climatic factors on fecal coliform levels
      in Mississippi Sound.
AB  - Information on the effects of inter-annual variations in climatic factors on
      fecal coliform levels in coastal waters is scarce. We used 11 years (1990-2001)
      of rainfall, water temperature, Pearl River stage and salinity data to assess the
      effects of the 1991-1992 and 1997-1998 El Nino events on fecal coliform levels in
      Mississippi Sound. El Nino-Southern Oscillation had major effects on Pearl River
      stage and water quality in the Sound. The geometric mean fecal coliform number
      differed among years (P = 0.0001), being highest during 1991-1992 El Nino years
      (14.22 MPN per 100 ml) and lowest during 1999-2000 La Nina years (<1.8 MPN per
      100 ml). Mean salinity varied among years (P = 0.0001) from 9 ppt (1991-1992) to
      21 ppt (1999-2000). Mean water temperature was lowest in 1997-1998 (14.5 degrees
      C) and highest in 1998-2000 (19.4 degrees C). Pearl River stage differed among
      years (P = 0.0001), ranging from 1.96 m (1999-2000) to 3.57 m (1997-1998).
      Inverse relationships were observed between fecal coliform levels and salinity
      (r(2) = 0.74; P = 0.001) and water temperature (r(2) = 0.69; P=0.001), whereas
      positive relationships were obtained with total rainfall (r(2) = 0.52; P = 0.013)
      and Pearl River stage (r(2) = 0.90; P = 0.0001). These relationships are useful
      for evaluating the potential effects of climate change on water quality and
      classification of shellfish growing waters in order to protect humans from
      consuming contaminated shellfish in shallow river-influenced estuaries.

PMID- 15556210
TI  - Removal of fulvic acid from water electrochemically using active carbon fiber
      electrode.
AB  - Humic acids (HA) are a group of widely existing natural organic compounds and
      potential contaminants to underground water reservoirs. Fulvic acid (FA) is a
      typical humic acid of relatively low molecular weight. Electrochemical removal of
      FA from water by active carbon fiber (ACF) electrodes was studied by using light
      scattering photometer (LSP), fluorescence spectroscopy and total organic carbon
      analyzer (TOC). The experiments showed that FA molecules aggregated and that the
      average particle diameter in FA solution increased from below 10 nm to hundreds
      of nanometers during the treatment process. When iron was added to the anode, the
      FA could be coagulated efficiently at the early stage of the treatment. The
      proposed mechanism of the removal process is: adsorption of FA on ACF surface -->
      aggregation of FA --> desorption of FA aggregates from ACF --> coagulation of FA
      aggregates by nFe(OH)(2).mFe(OH)(3) dissolved from anode. Experiments were also
      repeated using graphite and stainless-steel electrodes, and the results were
      compared with that of ACF electrodes. FA aggregation was not observed in these
      experiments and most FA was not removed from the solution. At the end of this
      paper, FA samples from Huai River sediment were successfully treated using the
      ACF electrode.

PMID- 15556211
TI  - Reduction of germination frequency in Anabaena akinetes by sediment drying: a
      possible method by which to inhibit bloom formation.
AB  - The effect of desiccation on germination frequency of Anabaena akinetes was
      investigated to evaluate the practical usefulness of sediment drying in
      reservoirs as a measure of inhibition of Anabaena bloom formation. Sediment
      samples taken from a small reservoir, where an abundance of Anabaena blooms occur
      every summer were desiccated in the outdoors and in an incubator at 5, 10, 15,
      and 25 degrees C. As a result, the germination frequency of Anabaena akinetes was
      strongly inhibited in comparison with that of Anabaena akinetes preserved in a
      refrigerator without desiccation as a control. Greater inhibition of Anabaena
      germination found at a higher temperature was examined, and almost all akinetes
      lost the ability of germination at 25 degrees C after 3 days of the desiccation
      treatment. Therefore, sediment drying is considered to be a useful measure to
      reduce periods and scales of Anabaena blooms, and its effect will be enhanced by
      performance during the warmer seasons.

PMID- 15556212
TI  - Behavior of trihalomethanes and haloacetic acids in a drinking water distribution
      system.
AB  - This investigation focused on the seasonal variation and spatial fate of
      chlorination disinfection by-products (CDBPs) in a drinking water distribution
      system located in a region where very significant seasonal variations in water
      temperature and surface water quality occur. The analysis of a large number of
      collected samples showed that the seasonal and geographical variations of both
      groups of CDBPs under study--trihalomethanes (THMs) and haloacetic acids (HAAs)-
      were particularly important in this region. THM levels in summer and fall were,
      on average, about five times higher than in winter, whereas average HAAs in
      spring were about four times higher than in winter. THMs increased and stabilized
      in the extremities of the distribution system, whereas HAAs begin to increase,
      and then decrease (mainly due to a reduction of dichloroacetic acid). This
      decrease was significantly higher in warm waters than in cold waters, which led
      to the hypothesis of microbial degradation of HAAs as water approaches the system
      extremities. In fact, regression models for the occurrence of both CDBPs showed
      that the residence time of water was one important parameter in explaining the
      fate of both CDBPs. The spatio-temporal portrait of both groups of CDBPs that was
      generated demonstrates that, due to their high intra-seasonal changes, the
      calculation of average annual levels of these substances for compliance with
      regulations can vary widely. The results used in the portrait of CDBP behavior
      are also relevant in terms of exposure assessment for future epidemiological
      studies on human reproductive outcomes in the region.

PMID- 15556213
TI  - Sorption-desorption behavior of triazine and phenylurea herbicides in Kishon
      river sediments.
AB  - Sorption and desorption hysteresis of widely applied triazine and phenylurea
      herbicides were studied for river sediments. Organic carbon normalized sorption
      coefficient (K(OC)) values for all herbicides were significantly higher for the
      sediment from the downstream region of the river vs. the upstream sediment. On
      the basis of the measured K(OC) values, the triazine herbicides can be arranged
      in the following order: terbutryn > terbuthylazine > ametryn > atrazine. Among
      the phenylurea herbicides, chlorotoluron exhibited higher sorption than
      isoproturon (K(OC) values of 137 vs. 60 and 228 vs. 125 L/kg for the upstream and
      downstream sediments, respectively). Moreover, chlorotoluron exhibited lower
      desorption potential as compared with isoproturon (apparent hysteresis index
      values were 0.2-0.3 for chlorotoluron vs. 0.6-0.9 for isoproturon, measured with
      the upstream sediment). High sorption affinity of chlorotoluron to the sediments
      is probably due to stronger H-bonding interactions of the herbicide molecules
      with the sorbents. For both phenylurea herbicides, desorption hysteresis
      increased with decrease in sorbed amount. This behavior was opposite to the
      hysteresis trend observed for the triazines. The Cl-triazines (atrazine and
      terbuthylazine) exhibited higher desorption hysteresis than the S-triazines
      (ametryn and terbutryn). Therefore, the apparent hysteresis index values
      calculated for the Cl-triazines were lower than the values of S-triazines (about
      0.4 and 0.7, respectively). Based on the relative strength of H-bonding
      interactions of Cl- and S-triazines with formate anion and on the desorption
      hysteresis data we suggest a gradient-derived hole-filling sorption mechanism for
      the triazine herbicides with the river sediments.

PMID- 15556214
TI  - Environmental factors influencing microcystin distribution and concentration in
      the Midwestern United States.
AB  - During May-September 2000-2001, physicochemical data were collected from 241
      lakes in Missouri, Iowa, northeastern Kansas, and southern Minnesota U.S.A., to
      determine the environmental variables associated with high concentrations of the
      cyanobacterial hepatotoxin microcystin (MC). The study region represents a south
      north latitudinal gradient in increasing trophic status, with total phosphorus
      (TP) and total nitrogen (TN) values ranging between 2-995 and 90-15870 microg/L,
      respectively. Particulate MC values, measured by ELISA, ranged from undetectable
      to 4500 ng/L and increased with increasing latitude. Despite latitudinal trends,
      environmental variables explained < 50% of the variation in MC values. Inspection
      of MC-TN and MC-Secchi bivariate plots revealed distinctly nonlinear trends,
      suggesting optima for maximum MC values. Nonlinear interval maxima regression
      indicated that MC-TN maxima were characterized by a unimodal curve, with maximal
      (> 2000 ng/L) MC values occurring between 1500 and 4000 microg/L TN. Above 8000
      microg/L TN all MC values were < 150 ng/L. MC-Secchi maxima were characterized by
      exponential decline, with maximal MC values occurring at Secchi depths < 2.5 m.
      The development of empirical relationships between environmental variables and MC
      values is critical to effective lake management and minimization of human health
      risks associated with the toxin. This study indicates MC values are linked to the
      physicochemical environment; however, the relationships are not traditional
      linear models.

PMID- 15556215
TI  - Monitoring behaviour of catabolic genes and change of microbial community
      structures in seawater microcosms during aromatic compound degradation.
AB  - The behaviour of microbial populations responsible for degradation of the
      aromatic compounds, phenol, benzoate, and salicylate, and changes of microbial
      community structures in seawater microcosms were analysed quantitatively and
      qualitatively using MPN-PCR and PCR-DGGE. The purpose of the study was to
      investigate the ecology of the entire microbial community during bioremediation.
      Bacterial populations possessing catechol 1,2-dioxygenase (C12O) DNA were
      evidently the primary degraders of phenol and benzoate, but others possessing
      catechol 2,3-dioxygenase (C23O) DNA increased to enhance substrate degradation
      under high-load conditions when the substrates were present for long periods.
      However, salicylate degradation was evidently facilitated by specific bacterial
      populations possessing C23O DNA. PCR-DGGE analyses suggested that bacterial
      populations already relatively dominant in the original microcosm contributed to
      phenol degradation. Bacteria composing a minor fraction of the original
      population apparently increased and contributed to benzoate degradation.
      Bacterial populations possessing C23O DNA were responsible for salicylate
      degradation, however, and different degrading bacteria were evidently selected
      for, depending on the initial salicylate concentration. Microbial community
      structure tended to be simplified by aromatic compound degradation. Thus,
      microbial monitoring can elucidate the behaviour of bacterial populations
      responsible for aromatic compound degradation and be used to assess the effects
      of bioremediation on intact microbial ecosystems.

PMID- 15556216
TI  - Alteration to lake trophic status as a means to control arsenic mobility in a
      mine-impacted lake.
AB  - The relationship between lake trophic status, sedimentary redox conditions and As
      mobility was examined in mine-impacted Balmer Lake, Canada. Under the current
      redox regime, the reductive dissolution of As-bearing Fe(III) oxyhydroxides
      occurs in close proximity to the sediment-water interface, resulting in the
      remobilization of dissolved As in the shallow porewaters to values as high as 8.5
      mg L(-1). The shallow depth of the oxic zone limits the extent to which As can be
      re-sorbed in the interfacial horizons, and as a result, a proportion of the
      remobilized As escapes into the water column where it poses a water quality
      concern. Examination of the relationship between summer average chlorophyll a and
      total P at spring overturn in the lake water column demonstrates that Balmer Lake
      is currently eutrophic as a result of mining-derived inputs of P (domestic
      waters) and N (blasting residues and cyanide breakdown products). The results
      suggest that actively pushing the system towards oligotrophy by reducing non
      natural P loadings to the system will decrease rates of in situ production and
      associated sediment oxygen demand, which will in turn result in increased
      thickness of the aerobic zone and enhanced As scavenging. Such conclusions are
      supported by porewater data which indicate that the flux of As to the water
      column is significantly reduced when the Fe(III) redox cline is situated at
      deeper sediment depths. In the absence of detailed P-loading data, it is
      recommended that P inputs be reduced to approximately 10% of the estimated pre
      mining P loading of approximately 200 kg yr(-1). This implies reducing the
      collective P-loadings from the two mine sites adjacent to the lake from the
      approximate current value (approximately 150 kg yr(-1)) to approximately 20 kg
      yr(-1). It is proposed that establishment of oligotrophy in the lake should
      significantly mitigate the current level of dissolved As in lake waters.

PMID- 15556217
TI  - Occurrence of nitrifiers and diversity of ammonia-oxidizing bacteria in
      developing drinking water biofilms.
AB  - We studied the population dynamics of nitrifying bacteria during the development
      of biofilms up to 233 or 280 days on polyvinylchloride pipes connected to two
      full-scale drinking water distribution networks supplying processed and
      chloraminated surface water. The numbers of nitrifiers in biofilms were
      enumerated at intervals of 10-64 days by the most probable number (MPN) method at
      waterworks and at several study sites in distribution network areas. The numbers
      of nitrifiers increased towards the distal sites. The highest detected MPN counts
      of ammonia-oxidizing bacteria (AOB) for study areas 1 and 7 were 500 MPN cm(-2)
      and 1.0 x 10(6) MPN cm(-2), and those of nitrite-oxidizing bacteria (NOB) 96 MPN
      cm(-2) and 2.2 x 10(3) MPN cm(-2), respectively. The diversity of AOB was
      determined by PCR amplifying, cloning and sequencing the partial ammonia
      monooxygenase (amoA) gene of selected biofilm samples presenting different
      biofilm ages. The PCR primers used, A189 and A682, also amplified a fragment of
      particulate methane monooxygenase (pmoA) gene of methane-oxidizing bacteria. The
      majority of biofilm clones (24 out of 30 studied) contained Nitrosomonas amoA
      like sequences. There were only two pmoA-like sequences of Type I methanotrophs,
      and four sequences positioned in amoA/pmoA sequence groups of uncultured
      bacteria. From both study area very similar or even completely identical
      Nitrosomonas amoA-like sequences were obtained despite of high difference in AOB
      numbers. The results show that the conditions in newly formed biofilms in
      drinking water distribution systems favor the growth of Nitrosomonas-type AOB.

PMID- 15556218
TI  - Contact-time-dependent atrazine residue formation in surface soils.
AB  - The formation of nonextractable atrazine residues was evaluated in sterilized
      agricultural and woodland soils pre-loaded with (14)C-atrazine for contact
      periods of 1 h (0.046 days), and 1, 7, 14, 28, 56, and 84 days. Extractability of
      the pre-loaded atrazine and nonextractable residue formation were determined by
      subjecting the soils to sequential fill-and-draw extractions with water,
      ethylacetate/water, and alkali. Nonextractable atrazine residues associated with
      the fulvic acid (FA), humic acid (HA) and humin/mineral (HM) components of soil
      were determined by separating FA and HA from the soils and measuring the (14)C
      activity associated with each fraction. Longer herbicide-soil contact times
      resulted in attenuated water extractability and enhanced nonextractable residue
      formation. At the longest contact periods, residues recovered in the FA, HA and
      HM components of soil accounted for 35-50% of the pre-loaded herbicide. The
      woodland soil contained significantly larger amounts of HA and humin than the
      agricultural soil, and appeared to have contributed significantly to
      nonextractable residue formation. Results from this study indicate that
      physicochemical processes occurring at intra-mineral and intra-organic matter
      sites continue to influence the fate of organic pesticides long after their
      application on soils.

PMID- 15556219
TI  - A practical application of Droop nutrient kinetics (WR 1883).
AB  - Algal growth kinetics based on internal phosphorus concentration were
      incorporated into an existing eutrophication model. Application to a closed
      system resulted in damped oscillations in algal biomass and phosphate relative to
      a model with fixed composition. Peak biomass did not differ substantially,
      however, from that attained using a model with fixed, minimal phosphorus-to
      carbon ratio. Sensitivity analyses were conducted following model application to
      the lower St. Johns River, Florida. Factor-of-two changes in key parameters had
      little influence on computed chlorophyll. Varying model parameters exerted a
      larger influence on dissolved phosphate concentration. We conclude Droop kinetics
      present a mechanism for regulating computed nutrient concentrations rather than
      computed chlorophyll concentrations.

PMID- 15556220
TI  - Removal of saxitoxins from drinking water by granular activated carbon, ozone and
      hydrogen peroxide--implications for compliance with the Australian drinking water
      guidelines.
AB  - In a laboratory-scale trial, we studied the removal of saxitoxins from water by
      ozone, granular activated carbon (GAC) and H(2)O(2), and considered the
      implications of residual toxicity for compliance with the Australian drinking
      water standards. Cell-free extracts of Anabaena circinalis were added to raw,
      untreated drinking water obtained from a water supply reservoir to provide a
      toxicity of 30 microg (STX equivalents)l(-1). Ozone alone, or in combination with
      H(2)O(2), failed to destroy the highly toxic STX and GTX-2/3, and only partially
      destroyed dc-STX, and the low-toxicity C-toxins and GTX-5. In all cases, the
      toxicity of the water was reduced by less than 10%. GAC removed all of the STX,
      dc-STX and GTXs, but only partially removed the C-toxins. However, the residual
      toxicity was reduced to the suggested Australian drinking water guideline
      concentration of 3 microg (STX equivalents)l(-1) without O(3) pre-treatment.
      Modelling the spontaneous chemical degradation of residual C-toxins following
      treatment shows that residual toxicity could increase to 10 microgl(-1) after 11
      d due to formation of dc-GTXs and would then gradually decay. In all, residual
      toxicity would exceed the Australian drinking water guideline concentration for a
      total of 50 d.

PMID- 15556221
TI  - The long-term nutrient accumulation with respect to anthropogenic impacts in the
      sediments from two freshwater marshes (Xianghai Wetlands, Northeast China).
AB  - Sediment cores, representing a range of watershed characteristics and
      anthropogenic impacts, were collected from two freshwater marshes at the Xianghai
      wetlands (Ramsar site no. 548) in order to trace the historical variation of
      nutrient accumulation. Cores were (210)Pb- and (137)Cs-dated, and these data were
      used to calculate sedimentation rates and sediment accumulation rates. Ranges of
      dry mass accumulation rates and sedimentation rates were 0.27-0.96 g m(-2)yr(-1)
      and 0.27-0.90 cm yr(-1), respectively. The effect of human activities on
      increased sediment accumulation rates was observed. Nutrients (TOC, N, P, and S)
      in sediment were analyzed and nutrient concentration and accumulation were
      compared in two marshes with different hydrologic regime: an "open" marsh (E-0)
      and a partly "closed" marsh (F-0). Differences in physical and chemical
      characteristics between sediments of "open" and partly "closed" marsh were also
      observed. The "open" marsh sequestered much higher amounts of TOC (1.82%), N
      (981.1 mg kg(-1)), P (212.17 mg kg(-1)), and S (759.32 mg kg(-1)) than partly
      "closed" marsh (TOC: 0.32%, N: 415.35 mg kg(-1), P: 139.64 mg kg(-1), and S:
      624.45 mg kg(-1)), and the "open" marsh indicated a rather large historical
      variability of TOC, N, P, and S inputs from alluvial deposits. Nutrient inputs
      (2.16-251.80 g TOC m(-2) yr(-1), 0.43-20.12 g N m(-2) yr(-1), 0.39-3.03 g P m(-2)
      yr(-1), 1.60-15.13 g S m(-2) yr(-1)) into the Xianghai wetlands of China are in
      the high range compared with reported nutrient accumulation rates for freshwater
      marshes in USA. The vertical variation, particularly for N, P, and S indicated
      the input history of the nutrients of the Xianghai wetlands developed in three
      periods--before 1950s, 1950-1980s, and after 1980s. The ratios between
      anthropogenic and natural inputs showed that the relative anthropogenic inputs of
      TOC, N, P, and S have been severalfold (TOC: 1.68-11.21, N: 0.47-3.67, P: 0.24
      1.36, and S: 1.46-2.96) greater than values of their natural inputs after 1980s.
      The result is probably attributable, in part, to two decades of surface coal
      mining activities, urban sewage, and agriculture runoff within the upstream
      region of the Huolin River. Our findings suggest that the degree of anthropogenic
      disturbance within the surrounding watershed regulates wetland sediment, TOC, N,
      P, and S accumulation.

PMID- 15556222
TI  - Modelling of runoff behaviour of particle-bound polycyclic aromatic hydrocarbons
      (PAHs) from roads and roofs.
AB  - Road and roof dust was collected and samples of runoff were taken at an urban
      storm sewer system in a residential area in Japan. Suspended solids (SS) in the
      runoff samples were classified into two fractions: fine (smaller than 45 microm)
      and coarse (larger than 45 microm). Runoff monitoring and chemical analysis data
      were also used to validate a runoff model for particle-bound polycyclic aromatic
      hydrocarbons (PAHs) that was originally developed to explain the behaviour of SS
      in the same area. The model, in which roads and roofs were considered separately
      as impervious surfaces, expressed the SS and particle-bound PAHs runoff behaviour
      for fine and coarse particles very well, except during and after heavy rainfalls
      (more than 10mm/h). However, the model could not explain the PAH profiles of
      runoff particles; the profiles of 12 PAH compounds tracked in this study were
      almost constant and more similar to those of road dust than roof dust throughout
      the event. An improved model is developed which explains the runoff behaviour by
      considering two types of road dust with different mobility.

PMID- 15556223
TI  - Regeneration of acid orange 7-exhausted granular activated carbons with microwave
      irradiation.
AB  - An investigation was performed for the regeneration of three granular activated
      carbons (GACs) exhausted with acid orange 7 (AO7). The three GACs were made from
      different materials, i.e. coconut shells, almond nucleus and coal. The AO7
      adsorption process was carried out in a continuous-flow adsorption column. After
      adsorption, the AO7-saturated GAC was dried at 120 degrees C, then regenerated in
      a quartz reactor by 2450 MHz microwave (MW) irradiation at 850 W for 5 min. The
      efficacy of this procedure was analyzed by determining the rates and amounts of
      AO7 adsorbed in successive adsorption-MW regeneration cycles. Effects of this
      regeneration on the structural properties, surface chemistry and the AO7
      adsorption capacities of GAC samples were examined. It was found that after
      several adsorption-MW regeneration cycles, the adsorption rates and capacities of
      GACs could maintain relatively high levels, even higher than those of virgin
      GACs, as indicated by AO7 breakthrough curves and adsorption isotherms. The
      improvement of GAC adsorption properties resulted from the modification of pore
      size distribution and surface chemistry by MW irradiation.

PMID- 15556224
TI  - Contribution of known endocrine disrupting substances to the estrogenic activity
      in Tama River water samples from Japan using instrumental analysis and in vitro
      reporter gene assay.
AB  - To quantitatively characterize the substances contributing to estrogenic activity
      in river water, in vitro bioassay using MVLN cells and instrumental analysis
      using liquid chromatograph-mass spectrometer (LC/MS) or liquid chromatograph
      tandem mass spectrometer (LC/MS/MS) were applied to river water extracts taken
      from various locations in the Tama River, Japan. Tama River water samples were
      extracted using solid phase extraction and the crude extracts were fractionated
      by high-performance liquid chromatography (HPLC) into 10 fractions. The sixth
      fraction contained nonylphenol (NP) and octylphenol (OP) at concentrations in the
      range of 51.6-147 and 6.9-81.9 ng/L, respectively (concentrations corresponding
      to the original sample volumes). No estrogenic activity, expressed as 17beta
      estradiol equivalents (E2-EQ(B)), however, was observed in this fraction (<0.6 ng
      E2eq/L). Instrumentally determined estrogenic activity (E2-EQ(C)), which is the
      concentrations of NP and OP multiplied by their corresponding relative potency,
      was below the detection limit of the MVLN cell bioassay. Estrogenic activities
      were detected only in HPLC fraction nos. 7, 8 and 9. Estrone (E1), estradiol (E2)
      and bisphenol A (BPA) were detected in these fractions. Estriol (E3) and
      ethynylestradiol (EE2) were not detected (<0.2 ng/L) in these fractions. The
      calculated E2-EQ(C) for BPA was below the detection limit of bioassay. The E2
      EQ(C) for E1 and E2 were on the same order as the estrogenic activity determined
      by the bioassay (E2-EQ(B)). The ratios of E2-EQ(C) and E2-EQ(B) for E1 and E2 in
      the three factions collectively (nos. 7-9) were 0.49-0.97 and 0.29-1.12,
      respectively. Above results indicated that the major causal substances to the
      estrogenic activity in the Tama River were E1 and E2.

PMID- 15556225
TI  - Modelling anaerobic biomass growth kinetics with a substrate threshold
      concentration.
AB  - Many bacteria have been observed to stop growing below a certain substrate
      threshold concentration. In this study, a modification of the Monod kinetics
      expression has been proposed to take into account this substrate threshold
      concentration observed in bacterial growth. Besides the threshold concentration
      no additional parameters have been added to the kinetic expression and so, only
      the substrate threshold concentration and the half-saturation constant have to be
      estimated for model calibration purposes. Furthermore, for parameter estimation
      purposes, practical identifiability of this new function has been studied and the
      results have been satisfactory. The new model has been applied, as an example, to
      a simple anaerobic model to simulate the competition for hydrogen between
      sulphate reducers and methanogens in a thermophilic methanol-fed bioreactor.
      Oscillatory behaviour and mathematical instabilities have been avoided by using
      the proposed model. Parameter sensitivities have also been calculated along the
      simulation period in order to investigate the importance of hydrogen threshold
      concentration parameters.

PMID- 15556226
TI  - Identification and understanding of fouling in low-pressure membrane (MF/UF)
      filtration by natural organic matter (NOM).
AB  - An understanding of natural organic matter (NOM) as a membrane foulant and the
      behavior of NOM components in low-pressure membrane fouling are needed to provide
      a basis for appropriate selection and operation of membrane technology for
      drinking water treatment. Fouling by NOM was investigated by employing several
      innovative chemical and morphological analyses. Source (feed) waters with a high
      hydrophilic (HPI) fraction content of NOM resulted in significant flux decline.
      Macromolecules of a relatively hydrophilic character (e.g. polysaccharides) were
      effectively rejected by low-pressure membranes, suggesting that macromolecular
      compounds and/or colloidal organic matter in the hydrophilic NOM fraction may be
      a problematic foulant of low-pressure membranes. Moreover, the significant
      organic fouling that is contributed by polysaccharides and/or proteins in
      macromolecular and/or colloidal forms depends on molecular shape (structure) as
      well as size (i.e. molecular weight). More significant flux decline was observed
      in microfiltration (MF) compared to ultrafiltration (UF) membrane filtration. MF
      membrane fouling may be caused by pore blockage associated with large
      (macromolecular) hydrophilic molecules and/or organic colloids. In the case of UF
      membranes, the flux decline may be caused by sequential or simultaneous processes
      of surface (gel layer) coverage during filtration. Morphological analyses support
      the notion that membrane roughness may be considered as a more important factor
      in membrane fouling by controlling interaction between molecules and the membrane
      surface, compared to the hydrophobic/hydrophilic character of membranes. Membrane
      fouling mechanisms are not only a function of membrane type (MF versus UF) but
      also depend on source (feed) water characteristics.

PMID- 15556227
TI  - Effects of oxygen on biodegradation of benzoate and 3-chlorobenzoate in a
      denitrifying chemostat.
AB  - A mixed microbial culture degraded a mixture of benzoate (863 mg/L), 3
      chlorobenzoate (3-CB) (69.7 mg/L), and pyruvate (244 mg/L) under denitrifying
      conditions in a chemostat. Biodegradation under denitrifying conditions was
      stable, complete (effluent concentrations below detection limits), and proceeded
      without the production of toxic intermediates like chlorocatechols. The addition
      of oxygen at mass input rates of 6.2%, 15.5%, and 43.9% of the mass input rate of
      chemical oxygen demand (COD) (337 mg COD/h) did not induce the synthesis of
      aerobic biodegradation pathways and thus did not disrupt biodegradation. Rather,
      the oxygen was used as a terminal electron acceptor, displacing a stoichiometric
      amount of nitrate, leading to microaerobic conditions (dissolved oxygen
      concentration <0.050 mg/L) in which oxygen utilization and denitrification
      occurred simultaneously. The reduction of nitrate occurred fully to N(2) gas with
      no accumulation of nitrite, nitrous oxide, or nitric oxide, although the ability
      of the culture to transfer electrons to the nitrogen oxides decreased as the
      oxygen input was increased. The anoxic benzoate uptake capability was unaffected
      by the increase in oxygen addition, but the anoxic 3-CB uptake capability
      increased, as did the level of benzoyl-CoA reductase in the cells.

PMID- 15556228
TI  - Comments on: removal of copper ions from aqueous solution by tree ferns.

PMID- 15556229
TI  - Formation of silk fibroin matrices with different texture and its cellular
      response to normal human keratinocytes.
AB  - Three forms of silk fibroin (SF) matrices, woven (microfiber), non-woven
      (nanofiber), and film form, were used to perform a conformational analysis and
      cell culture using normal human oral keratinocytes (NHOK). To obtain the SF
      microfiber (SF-M) matrix, natural grey silk was degummed, while the SF film (SF
      F) and nanofiber (SF-N) matrices were prepared by casting and electrospinning the
      formic acid solutions of the regenerated SF, respectively. For insolubilization,
      as-prepared SF-F and SF-N matrices were chemically treated with an aqueous
      methanol solution of 50%. The conformational structures of as-prepared and
      chemically treated SF matrices were investigated using attenuated total
      reflectance infrared spectroscopy (ATR-IR) and solid-state 13C CP/MAS nuclear
      magnetic resonance (NMR) spectroscopy. The as-cast SF-F matrix formed a mainly
      beta-sheet structure that was similar to the SF-M matrix, whereas the as-spun SF
      N matrix had a random coil conformation as the predominant secondary structure.
      Conformational transitions from random coil to beta-sheet of the as-spun SF-N
      occurred rapidly within 10 min following aqueous methanol treatment, and were
      confirmed by solid-state 13C NMR analysis. To assess the cytocompatibility and
      cells behavior on the different textures of SF, we examined the cell attachment
      and spreading of NHOK that was seeded onto the SF matrices, as well as the
      interaction between the cells and SF matrices. Our results indicate that the SF
      nanofiber matrix may be more preferable than SF film and SF microfiber matrices
      for biomedical applications, such as wound dressings and scaffolds for tissue
      engineering.

PMID- 15556230
TI  - Molecular mass and antitumor activities of sulfated derivatives of alpha-glucan
      from Poria cocos mycelia.
AB  - Two kinds of water-insoluble (1-->3)-alpha-D-glucan samples, ab-PCM3-I and ac
      PCM3-I, isolated from different Poria cocos mycelia were sulfated, to produce two
      series of water-soluble derivatives ab-PCM3-I-S1-S5 and ac-PCM3-I-S1-S5,
      respectively. The derivatives having different weight-average molecular mass (Mw)
      were produced by changing reaction temperature and time as well as molar ratios
      between chlorosulfonic acid and number of hydroxyl groups in the glucan. The
      degrees of substitution (DS) of the sulfated derivatives were analyzed by
      elemental analysis (EA) to be 0.39-0.67 for ab-PCM3-I-S and 0.73-0.96 for ac-PCM3
      I-S, respectively. The Mw and the intrinsic viscosity ([eta]) of the samples ab
      PCM3-I-S and the ac-PCM3-I-S were measured by size exclusion chromatography
      combined with laser light scattering (SEC-LLS) and viscometry in phosphate buffer
      solution (PBS) at 37 degrees C. The results indicated that their Mw ranged from
      2.0 to 11.3 x 10(4) for the samples ab-PCM3-I-S, and 4.7 to 40.0 x 10(4) for the
      samples ac-PCM3-I-S. Moreover, the antitumor activities of the sulfated
      derivatives ab-PCM3-I-S and ac-PCM3-I-S against Sarcoma 180 tumor cell tested
      both in vitro and in vivo are significantly higher than those of the native alpha
      D-glucans. Therefore, a moderate range of molecular mass from 2.0 x 10(4) to 40.0
      x 10(4), relatively high chain stiffness and good water solubility of the
      sulfated derivatives are beneficial to the enhancement of their antitumor
      activities.

PMID- 15556231
TI  - Inter-specific sequence conservation and intra-individual sequence variation in a
      spider silk gene.
AB  - Currently, studies on major ampullate spidroin 1 (MaSp1) genes of non-orb weaving
      spiders are few, and it is not clear whether genes of these organisms exhibit the
      same characteristics as those of orb-weavers. In addition, many studies have
      proposed that MaSp1 might be a single gene with allelic variants, but supporting
      evidence is still lacking. In this study, we compared partial DNA and amino acid
      sequences of MaSp1 cloned from different spider guilds. We also cloned partial
      MaSp1 sequences from genomic DNA and cDNA of the same individuals of spiders
      using the same primer combination to see if different molecular forms existed. In
      the repetitive region of partial MaSp1 sequences obtained, GGX, GA and poly-A
      motifs were present in all Araneomorphae and Mygalomorpae species examined. An
      extreme similarity in MaSp1 non-repetitive portions was found in sequences of
      ecribellate, cribellate and Mygalomorphae web-builders and such a result
      suggested that this sequence might exhibit an important function. A comparison of
      sequences amplified from the same individual showed that substitutions in amino
      acids occurred in both repetitive and non-repetitive regions, with a much higher
      variation in the former. These results suggest that the MaSp1 of Araneomorphae
      spiders exhibits several forms in an individual spider and it might be either a
      multiple gene or a single gene with a multiple exon/intron organization.

PMID- 15556232
TI  - DNA interaction with biologically active divalent metal ions: binding constants
      calculation.
AB  - In our previous work we have shown that under the action of Cu2+, Mn2+ and Ca2+
      ions DNA is able to transit into a compact state in aqueous solution. In the
      present work we carried out calculations of binding constants for divalent metal
      ions interacting with DNA in terms of the macromolecule statistical sum. The
      formula for calculation of the binding constants and cooperativity parameters was
      proposed. It was shown that on the "coil state"-"compact (globule) state"
      transition a single DNA molecule may undergo the first-order phase transition
      while the transition of the assembly of average DNA chains is of sigmoidal
      character typical of the cooperative and continuous transition.

PMID- 15556233
TI  - Structural investigation of amylose complexes with small ligands: inter- or intra
      helical associations?
AB  - Highly crystalline amylose complexes with menthone (1) and linalool (2) were
      analysed by wide-angle X-ray diffraction and solid-state nuclear magnetic
      resonance (NMR). The complexes, after partial water desorption in a controlled
      atmosphere (aw=0.75), displayed a typical V-isopropanol structure, showing the
      presence of ligand inside or between the helices in the crystalline domains.
      Sequential washing of the powdered complexes with ethanol before and after
      desorption permitted probing the intra- and inter-helical inclusions. High
      resolution magic angle spinning (HRMAS) recordings were used to compare the
      chemical shifts of free and bound aroma which allowed a proposal that some
      hydrogen bonding is involved in the amylose complexing. Moreover, it showed that
      free aroma was completely removed by ethanol washing. Using cross polarization
      magic angle spinning (CPMAS) and X-ray scattering experiments, it was
      demonstrated that the V-isopropanol type was retained for linalool whatever the
      treatment used. On the contrary, the measurement shifts toward the V-6I amylose
      hydrate (V-h) type for menthone after ethanol washing before the desorption step,
      reflecting the disappearance of inter-helical associations between menthone and
      amylose. The stability of the complex prepared with linalool shows that this
      ligand is more strongly associated to amylose helices. The discrepancies observed
      in the chemical shifts attributed to carbons C1 and C4 in CPMAS spectra of V
      isopropanol and V-h forms could be attributed either to a deformation of the
      single helix (with possible inclusion of the ligand inside) or to the presence of
      the ligand between helices (only water molecules are present in the V-h form).

PMID- 15556234
TI  - X-ray structural study of noncrystalline regenerated Bombyx mori silk fibroin.
AB  - X-ray diffraction measurements of regenerated Bombyx mori silk fibroin were
      carried out to determine its structural characteristic from an analysis of
      differential radial distribution functions (DRDFs). The temperature dependence of
      X-ray diffraction patterns from noncrystalline and crystal structures of
      regenerated silk fibroin was investigated using a high temperature furnace. Time
      resolved X-ray diffraction profiles were also obtained to construct kinematical
      models of structural changes caused by the addition of water. DRDFs, calculated
      from the experimental data, were compared with the DRDFs simulated on the basis
      of the Monte Carlo method. In order to model the noncrystalline structures,
      structural units were assumed to be parts of the crystalline structure of silk
      and those with appropriate structural defects reported previously. From the
      comparison of experimental and simulated DRDFs, it was determined that
      noncrystalline regenerated silk consisted of locally ordered atomic sheets
      similar to the atomic arrangement in the silk I crystal (Type-I sheets), and the
      final state of the structural change was noncrystalline, consisting of small
      crystallites, the structure of which is similar to that of silk II (Type-II
      crystallites). Time resolved DRDFs were also qualitatively interpreted by both
      the ordering of Type-I sheets and structural changes from Type-I to Type-II. The
      formation of the small Type-II crystallites obtained in this study was consistent
      with the nucleation of silk II by birefringence measurements of silk glands and
      the spinneret of Bombyx mori silkworm reported previously. X-ray diffraction
      should be a useful technique to understand the structural characteristics of
      noncrystalline organic materials.

PMID- 15556235
TI  - Lattice deformation and thermal stability of crystals in spider silk.
AB  - The X-ray diffraction of dragline silks, produced by Nephila and Cyrtophora
      spiders, were measured by synchrotron radiation in their original states or in
      situ during stretching and heating. Nephila pilipes spiders construct a two
      dimensional orb web that must be rebuilt in one or 2 days, but Cyrtophora spiders
      form a three-dimensional tent web that can exist for several weeks in a tropical
      forest. Diffraction patterns of N. pilipes and Cyrtophora draglines resemble each
      other. Crystals of two kinds are identified in these draglines; one is aligned
      parallel to the silk direction and another is less oriented. The less oriented
      crystal in Cyrtophora dragline is aligned better than that in N. pilipes
      dragline, which generates about three times stronger diffract intensity. Crystals
      in N. pilipes and C. moluccensis dragline silks have remarkable thermal
      stability. Equatorial reflections remain undiminished until 350 and 450 degrees C
      for N. pilipes and C. moluccensis, respectively. In contrast, the meridional
      reflections S and (002), which are parallel to the silk thread, disappear at a
      temperature less than 100 degrees C for C. moluccensis but remain for Nephila up
      to 100 degrees C. Meridional reflections S and (002) shift to a smaller angle
      during stretching, whereas equatorial reflections remain constant in a range 1.0
      1.3 times the original length. The position of the S reflection shifts rapidly in
      the first 10% of elongation from the original length but remains constant during
      subsequent stretching, whereas the (002) reflection shifts rapidly during the
      first 5% elongation from the original length and continues to shift subsequently.
      In contrast, the features of N. pilipes dragline alter insignificantly during
      stretching. Examination of the composition of amino acids of the draglines of N.
      pilipes and C. moluccensis indicates that a dragline of N. pilipes contains more
      glycine, but much less alanine, than that of C. moluccensis.

PMID- 15556236
TI  - Binding of genistein to human serum albumin demonstrated using tryptophan
      fluorescence quenching.
AB  - Genistein is an isoflavone and phytoestrogen that is a potent inhibitor of cell
      proliferation and angiogenesis. This study was designed to investigate the
      binding of genistein to human serum albumin (HSA) under physiological conditions
      with drug concentrations in the range of 6.7 x 10(-6) to 2.0 x 10(-5) mol L(-1)
      and HSA concentration at 1.5 x 10(-6) mol L(-1). Fluorescence quenching methods
      in combination with Fourier transform infrared (FT-IR) spectroscopy and circular
      dichroism (CD) spectroscopy was used to determine the binding mode, the binding
      constant and the protein structure changes in the presence of genistein in
      aqueous solution. Changes in the CD spectra and FT-IR spectra were observed upon
      ligand binding, and the degree of tryptophan fluorescence quenching change did
      significantly in the complexes. These data have proved the change in protein
      secondary structure accompanying ligand binding. The change in tryptophan
      fluorescence intensity was used to determine the binding constants. The
      thermodynamic parameters, the enthalpy change (DeltaH) and the entropy change
      (DeltaS) were calculated to be -22.24 kJ mol(-1) and 19.60 J mol(-1) K(-1)
      according to the van't Hoff equation, which indicated that hydrophobic and
      electrostatic interactions play the main role in the binding of genistein to HSA.

PMID- 15556237
TI  - Cut-point shift and index shift in self-reported health.
AB  - There is some concern that ordered responses on health questions may differ
      across populations or even across subgroups of a population. This reporting
      heterogeneity may invalidate group comparisons and measures of health inequality.
      This paper proposes a test for differential reporting in ordered response models
      which enables to distinguish between cut-point shift and index shift. The method
      is illustrated using Canadian National Population Health Survey data. The
      McMaster Health Utility Index Mark 3 (HUI3) is used as a more objective health
      measure than the simple five-point scale of self-assessed health. We find clear
      evidence of index shifting and cut-point shifting for age and gender, but not for
      income, education or language.

PMID- 15556238
TI  - Investigating the social value of health changes.
AB  - This survey has demonstrated that the Danish public is concerned with
      distributional aspects of health gains. They have a strong inclination to give
      priority to those in a more severe health state provided their expected benefits
      are large enough to bring them to the health level where their rival patients are
      without treatment. Results also indicated that the equity argument may not apply
      with equal force on all health dimensions. Respondents did to some extent trade
      off equity for greater health gains. A nouvelle finding is that the valuations of
      health increments per se seem to be affected by whether questions are framed as
      individual or social choices. If social decision making is the issue, health
      gains which involve relieving patients of extreme problems are valued more highly
      than relief of minor ailments. These discrepancies between individual and social
      valuations suggest that the use of QALY values elicited from an individual's
      perspective may not be valid in social decision making.

PMID- 15556239
TI  - An empirical analysis of milk addiction.
AB  - We show the estimable rational addiction model tends to yield spurious evidence
      in favor of the rational addiction hypothesis when aggregate data are used.
      Direct application of the canonical model yields results seemingly indicative
      that non-addictive commodities such as milk, eggs, and oranges are rationally
      addictive. Monte Carlo simulation demonstrates that such results are likely to
      obtain whenever the commodity under scrutiny exhibits high serial correlation, or
      when even a small amount of the variation in prices is endogenous, or when
      overidentified instrumental variables estimators are used, or when commonly
      imposed restrictions are employed. We conclude that time-series data will often
      be insufficient to differentiate rational addiction from serial correlation in
      the consumption series.

PMID- 15556240
TI  - Are novel drugs more risky for patients than less novel drugs?
AB  - The Food and Drug Administration has accelerated the approval of therapeutically
      novel drugs so that patients have faster access to innovative drug therapies.
      Little research, however, has examined the variation in risks among
      therapeutically novel and less novel drugs. Do drugs that represent greater
      novelty also entail greater risks for patients? This paper uses post-marketing
      drug safety surveillance data from the FDA to examine the adverse drug reactions
      (ADRs) associated with novel and less novel drugs. Negative binomial regressions
      are used to examine the impact of a drug's FDA novelty rating on its ADR count
      controlling for differences in drug utilization, the conditions being treated,
      disease characteristics, patient characteristics, drug review times, and year
      specific effects. Results show that drugs deemed novel by the FDA are associated
      with a greater number of serious drug reactions, including those that result in
      hospitalization and death, than less novel drugs. These results suggest that
      novel drugs pose greater risk of serious ADRs for patients relative to less novel
      drugs.

PMID- 15556241
TI  - Informal care and health care use of older adults.
AB  - Informal care by adult children is a common form of long-term care for older
      adults and can reduce medical expenditures if it substitutes for formal care. We
      address how informal care by all children affects formal care, which is
      critically important given demographic trends and the many policies proposed to
      promote informal care. We examine the 1998 Health and Retirement Survey (HRS) and
      1995 Asset and Health Dynamics Among the Oldest-Old Panel Survey (AHEAD) using
      two-part utilization models. Instrumental variables (IV) estimation controls for
      the simultaneity of informal and formal care. Informal care reduces home health
      care use and delays nursing home entry.

PMID- 15556242
TI  - How is mortality affected by money, marriage, and stress?
AB  - It is believed that the length of a person's life depends on a mixture of
      economic and social factors. Yet the relative importance of these is still
      debated. We provide recent British evidence that marriage has a strong positive
      effect on longevity. Economics matters less. After controlling for health at the
      start of the 1990s, we cannot find reliable evidence that income affects the
      probability of death in the subsequent decade. Although marriage keeps people
      alive, it does not appear to work through a reduction of stress levels. Greater
      levels of psychological distress (as measured by General Health Questionnaire
      (GHQ) stress scores) cannot explain why unmarried people die younger. For women,
      however, we do find that mental strain itself is dangerous. High GHQ stress
      scores help to predict the probability of an early death.

PMID- 15556243
TI  - Air pollution, health, and socio-economic status: the effect of outdoor air
      quality on childhood asthma.
AB  - This paper estimates the effect of air pollution on child hospitalizations for
      asthma using naturally occurring seasonal variations in pollution within zip
      codes. Of the pollutants considered, carbon monoxide (CO) has a significant
      effect on asthma for children ages 1-18: if 1998 pollution levels were at their
      1992 levels, there would be a 5-14% increase in asthma admissions. Also,
      households respond to information about pollution with avoidance behavior,
      suggesting it is important to account for these endogenous responses when
      measuring the effect of pollution on health. Finally, the effect of pollution is
      greater for children of lower socio-economic status (SES), indicating that
      pollution is one potential mechanism by which SES affects health.

PMID- 15556244
TI  - Risk selection and the specification of the conventional risk adjustment formula.
AB  - We argue that a sharp distinction must be made between the empirical problem of
      finding the best equation for explaining medical expenditures and the normative
      question of deriving capitations which give health plans the appropriate
      incentives. We propose a procedure, taken from the social choice literature, to
      go from the estimated equations to the capitations. If the estimated equations
      are not additively separable in legitimate and illegitimate risk-adjusters, it is
      impossible to remove all incentives for risk selection while respecting at the
      same time a straightforward requirement of horizontal equity. This has immediate
      implications for the choice of the functional form. Moreover, in so far as the
      conventional risk adjustment literature only includes so-called "legitimate" risk
      adjusters in the estimations, its results may suffer from omitted variables-bias.
      We illustrate our general methodological points with empirical results, obtained
      from a cross-section of 321,111 Belgian patients.

PMID- 15556245
TI  - Provider-client interactions and quantity of health care use.
AB  - This paper considers three types of provider-client interactions that influence
      quantity of health care use: rationing, effort, and persuasion. By rationing, we
      refer to a quantity limit set by a provider; effort, the productive inputs
      supplied by a provider to increase a client's demand; persuasion, the
      unproductive inputs used by a provider to induce a client's demand. We construct
      a theoretical model incorporating all three mechanisms as special cases. When the
      general model is specialized into one of three mechanisms, a set of empirical
      implications emerges. We test for the presence of each mechanism using data of
      patients receiving outpatient treatment for alcohol abuse in the Maine Addiction
      Treatment System. We find evidence for rationing and persuasion, but not effort.

PMID- 15556246
TI  - A stated preference approach to assessing health care-quality improvements in
      Palestine: from theoretical validity to policy implications.
AB  - User fees have been promoted as a potential complementary funding mechanism for
      health care in developing countries. In this paper, we appraise the use of
      contingent valuation (CV) as a tool to help develop user fees schemes that could
      be used to assist in allocating, and partially fund, health care. A random sample
      of 499 patients seeking care in primary health care centers, in Palestine, were
      asked to reveal their willingness to pay values for specified improvements in the
      quality of delivered medical care. Empirical analysis suggests that, in this
      context, CV can lead to internally consistent results and useful policy
      implications.

PMID- 15556247
TI  - HPN=Home palliative care?

PMID- 15556248
TI  - Acute and "chronic" phase reaction-a mother of disease.
AB  - The world is increasingly threatened by a global epidemic of chronic diseases.
      Almost half of the global morbidity and almost two thirds of global mortality is
      due to these diseases-approximately 35 million die each year from chronic
      diseases. And they continue to increase. Increasing evidence suggest that these
      diseases are associated with lifestyle, stress, lack of physical exercise, over
      consumption of calorie-condensed foods rich in saturated fat, sugar and starch,
      but also under-consumption of antioxidant-rich fruits and vegetables. As a result
      the function of the innate immune system is severe impaired. This review
      discusses the changes induced in response to mental and physical stress and their
      association with the subsequent development of metabolic syndrome, and its
      association with various chronic diseases. The endothelial cells and their
      function appears to be of great importance, and the function of their cellular
      membranes of special importance to the function of the underlying cells; their
      ability to obtain nutrients and antioxidants and to eliminate waste products. The
      abdominal adipocytes seen to play a key role, as they have the ability to in
      stressful situations release much of proinflammatory cytokines, PAI-1 and free
      fatty acids compared to elsewhere in the body. The load on the liver of these
      various substances in often of greater magnitude than the liver can handle. Some
      of the most common chronic diseases and their potential association with acute
      and "chronic" phase response, and with metabolic syndrome are discussed
      separately. The need for studies with lifestyle modifications is especially
      emphasized.

PMID- 15556249
TI  - Dietary advice and nutritional supplements in the management of illness-related
      malnutrition: systematic review.
AB  - BACKGROUND AND AIMS: This review investigated whether dietary advice to improve
      nutritional intake in adults with illness-related malnutrition improved
      mortality, morbidity, weight and energy intake, and whether oral nutritional
      supplements gave additional benefit, when given in combination with dietary
      advice. METHODS: Systematic review of randomised controlled trials comparing
      dietary advice with either (i) no advice, (ii) nutritional supplements or (iii)
      dietary advice plus nutritional supplements, in people with illness-related
      malnutrition. RESULTS: Twenty-four trials (25 comparisons) met the inclusion
      criteria, including 2135 randomised participants. Duration of follow-up ranged
      from 16 days to 24 months. There was no significant difference in mortality or
      morbidity for each comparison. Groups receiving supplements gained significantly
      more weight (or lost significantly less weight) than those who received dietary
      advice, weighted mean difference 1.09 kg (0.29-1.90) (4 studies). There were no
      significant differences in weight and energy intake between groups for the other
      comparisons. Few data were available for other outcomes. CONCLUSIONS: Nutritional
      supplements may have a greater role than dietary advice in the short-term
      improvement of body weight in illness-related malnutrition. There is a lack of
      evidence to support dietary advice in the management of illness-related
      malnutrition, but this is based on few, often poor quality, studies.

PMID- 15556250
TI  - The path from oral nutrition to home parenteral nutrition: a qualitative
      interview study of the experiences of advanced cancer patients and their
      families.
AB  - BACKGROUND AND AIM: Little is known about the perspectives that patients with
      advanced cancer and their family members have concerning nutritional problems and
      nutritional support. The aim of this study was to investigate their experiences
      of the nutritional situation prior to introduction of home parenteral nutrition
      (HPN) in order to understand factors contributing to the decision to accept HPN.
      METHODS: Semi-structured interviews were conducted with 13 patients with advanced
      cancer who had received HPN and 11 family members. The constant comparative
      method was used for data analysis. RESULTS: Patients and family members described
      the nutritional situation prior to HPN as a source of worry and often
      desperation. Patients reported wanting and trying to eat, but being unable to do
      so. Family members experienced powerlessness and frustration, as they could not
      enable the patient to eat. A lack of attention to nutritional problems by the
      hospital staff was described. The offer of HPN came when patients and family no
      longer felt able to solve the nutritional problems within the family. CONCLUSION:
      The desperate and chaotic nutritional situation in the family led to willingness
      to accept HPN. Because of the severity of the problems, HPN was viewed as a
      positive alternative.

PMID- 15556251
TI  - Bone mineral density in patients on home parenteral nutrition: a follow-up study.
AB  - BACKGROUND AND AIMS: The variations of bone mineral density (BMD) during home
      parenteral nutrition (HPN) and their relationship with general, life style,
      primary disease and HPN risk factors were investigated by a follow-up study.
      DESIGN: Patients who had BMD assessment in a previous cross-sectional survey
      underwent a 2nd BMD at femoral neck (FN) and lumbar spine (LS). Data about risk
      factors were collected by a structured questionnaire. BMD Z-score (number of
      standard deviations from normal values corrected for sex and age) and the
      annualized percent BMD change were analysed. RESULTS: Sixty-five adult patients
      were enrolled (follow-up: 18.1+/-5.5 months). The mean BMD Z-score significantly
      increased at the LS (P = 0.040) and remained unchanged at FN. In multiple
      regression analysis, the variations of the LS Z-score during HPN negatively
      correlated with the female sex (P = 0.021) and the age at starting HPN (P =
      0.022). The analysis of the annualized percent BMD change confirmed the results
      obtained by the analysis of the Z-score. No factor was associated with BMD
      variation at FN. CONCLUSIONS: HPN was not associated with a decrease of BMD in
      most of the patients; LS BMD Z-score variations were related to general risk
      factors rather than to HPN factors, showing a negative association with age and
      female sex.

PMID- 15556252
TI  - Absorption of enterally administered N-acetyl-l-glutamine versus glutamine in
      pigs.
AB  - BACKGROUND AND AIMS: Glutamine instability in liquid media suggests that
      evaluation of reasonable enteral nutrition sources of glutamine is needed. N
      acetyl-l-glutamine offers no instability and no intolerance problems. This
      research was conducted to study the absorption and apparent digestibility of
      glutamine versus N-acetyl-l-glutamine. METHODS: Two pig models were used. (1) In
      a clamped jejunal loop experiment, we measured the concentrations of glutamine
      and N-acetyl-l-glutamine in the intestinal infused solutions, intestinal mucosa,
      and portal and peripheral blood. (2) In a feeding experiment, we determined their
      apparent digestibility. RESULTS: N-acetyl-l-glutamine ( approximately 76%) was
      slightly less absorbed than glutamine ( approximately 85%) from the intestinal
      lumen into mucosa, where it was not detected as intact molecule, suggesting
      almost complete hydrolysis during absorption. Virtually no intact N-acetyl-l
      glutamine was observed in the blood compartments; glutamine from lumenal N-acetyl
      l-glutamine had the same behavior as that from lumenal-free glutamine in portal
      and peripheral blood. The apparent ileal digestibility of N-acetyl-l-glutamine
      was lower than that of free glutamine, as N-acetyl-l-glutamine was probably
      retained in the intestinal lumen to a greater extent than glutamine. CONCLUSION:
      N-acetyl-l-glutamine appeared to be a good candidate for glutamine fortification
      of enteral nutrition formulas.

PMID- 15556253
TI  - Application of three-dimensional body scanner: observation of prevalence of
      metabolic syndrome.
AB  - BACKGROUND AND AIMS: This retrospective cross-sectional study correlates blood
      pressure, blood glucose, lipid and uric acid levels with anthropometric
      measurements. METHODS: A total of 3975 visitors to the Department of Health
      Management were randomly selected to participate in this cross-sectional study.
      Whole body three-dimensional (3-D) laser scans were used to obtain anthropometric
      measurements. A health index (HI) was also designed based on anthropometric
      parameters. Subjects were defined as having metabolic syndrome when three of the
      following criteria were met: obesity (BMI of at least 30 kg/m(2); or a WHR of
      over 0.9 for males and 0.85 for females); triglyceride of at least 150 mg/dl;
      high-density lipoprotein (HDL)-cholesterol below 35 mg/dl for males and 39 mg/dl
      for females; fasting sugar levels of at least 110 mg/dl and hypertension.
      RESULTS: Of 3975 subjects, 341 (8.6%) met the criteria for diabetes mellitus
      (DM); of these, 32.8% were diagnosed with hypertension. This proportion exceeded
      18% of the subjects had normal glucose levels. Of the 3975 subjects, 658 (16.6%)
      met the criteria for metabolic syndrome. Proportionally, more male subjects than
      female subjects were diagnosed with metabolic syndrome (18.5% vs 14.7%). Of
      these, central obesity, elevated triglyceride and low HDL-cholesterol were the
      main factors in men, while fasting glucose, hypertension and central obesity were
      the main factors in women. This investigation found that larger proportions of
      subjects with impaired glucose tolerance (41.1%) and DM (64.2%) than of subjects
      with normal glucose subjects, suffered from metabolic syndrome (9.5%).
      CONCLUSIONS: 3-D body scanning is useful in correlating pertinent factors with
      metabolic syndrome, these factors include central obesity, hyperglycemia,
      dyslipidemia, hyperuricemia and hypertension.

PMID- 15556254
TI  - In vitro modulation of inflammatory cytokine production by three lipid emulsions
      with different fatty acid compositions.
AB  - BACKGROUND AND AIMS: Studies have suggested that 100% long-chain triacylglycerols
      (LCTs) lipid emulsions exhibit immunosuppressive effects, sometimes suspected to
      favor infectious complications in patients receiving parenteral nutrition. Newer
      emulsions, in particular olive oil-based emulsions, seem to have lesser
      immunosuppressive effects. We studied the in vitro effect of 100% LCTs
      (Intralipide), 50% LCTs-50% medium chain triacylglycerols (Medialipide), and 80%
      olive oil-based lipid emulsions (ClinOleic) on inflammatory cytokines production
      by peripheral blood mononuclear cells (PBMCs). METHODS: PBMCs separated by
      gradient centrifugation, or whole blood, were incubated with 0.001%, 0.01%, 0.1%
      and 1% of the three tested lipid emulsions during 24h in the presence or absence
      of activation by lipopolysaccharide and phytohemagglutinin. Then, supernatants
      were collected and cytokines measured (ELISA). RESULTS: The three lipid emulsions
      reduced basal TNF-alpha and IL-1beta production in PBMCs and whole blood
      cultures. However, ClinOleic was significantly less powerful in TNF-alpha and IL
      1beta inhibition by isolated PBMCs than Intralipide and Medialipide. Basal TNF
      alpha production was equally inhibited by the three emulsions in whole blood, but
      IL-1beta production was not significantly modified by ClinOleic. Interleukin-6
      and -8 were not affected. After cell activation, lipid emulsions exhibit no
      effect on cytokines production. CONCLUSION: ClinOleic induces a significantly
      lower in vitro inhibition of TNF-alpha and IL-1beta production by PBMCs than 100%
      LCTs or 50% LCTs-50% MCTs emulsions, and therefore might be more immune neutral.
      These effects vary from one subject to another, and disappeared after cell
      activation. Therefore, caution must be taken before extrapolation in vivo.
      Provided information should be taken into account for future design of clinical
      trials studying the immune modulating properties of lipid emulsions.

PMID- 15556255
TI  - Eating and dietary intake in communication-impaired stroke survivors: a cohort
      study from acute-stage hospital admission to 6 months post-stroke.
AB  - BACKGROUND AND AIMS: Stroke is a major cause of chronic morbidity but despite the
      importance of nutrition for recovery and rehabilitation, nutritional features
      have received limited attention, particularly amongst those with communication
      impairments. This study reports a group of patients followed through acute
      hospital admission and at 6 months post-stroke. METHODS: Subjects were survivors
      of a consecutive cohort admitted to a South London hospital with clinical
      diagnosis of acute stroke March-August 2001, with motor and communication
      deficits at initial assessment. Sequential assessments were undertaken from one
      week after admission to hospital discharge; then in normal residence at 6 months.
      Assessments focused on stroke-related impairments; functional abilities in
      activities of daily living and eating; nutritional indices; dietary intake
      derived from food diaries maintained by carers. Local Research Ethics Committee
      approval was obtained. RESULTS AND CONCLUSION: Thirty-six participants were
      studied in hospital; 18 at 6 months. Severely impaired and disabled at initial
      assessment (median Barthel Index score 1), significant improvements occurred by
      hospital discharge (to median score 7) despite substantial nutritional
      inadequacies and significant body tissue loss; mean energy intake met 60%
      Estimated Average Requirements. At 6 months the median Barthel Index score of
      survivors was 12.5 but multiple eating-related difficulties persisted, linked
      with dietary deficits; mean energy intake was 81% of Estimated Average
      Requirements. Body tissue losses continued across domiciliary settings. Closer
      attention to assessment and monitoring of nutrition-related aspects of stroke
      management is warranted across the continuum of care.

PMID- 15556256
TI  - Control of diarrhea by fiber-enriched diet in ICU patients on enteral nutrition:
      a prospective randomized controlled trial.
AB  - BACKGROUND AND AIMS: Enteral fiber-free diets alter intestinal transit and
      produce diarrhea or constipation. This prospective double blind, controlled study
      evaluates the use of guar gum, a soluble fiber and a candidate prebiotic in
      enteral feeds, to prevent diarrhea and potential health benefits in intensive
      care unit patients. METHODS: Twenty patients on enteral nutrition with persistent
      diarrhea were randomized to receive a new enteral feed either enriched with 2%
      soluble guar gum (study group, n = 10) or fiber-free (control group, n = 10) for
      4 successive days. RESULTS: The number of liquid stools in response to a soluble
      fiber-enriched diet was 2.0+/-0.9 (first day) vs. 1.0+/-0.7 (fourth day) (P <
      0.01), and in the control group 1.2+/-0.7 (first day) vs. 2.1+/-0.8 (fourth day)
      (P < 0.05). In the fiber-enriched feed group, plasma glucose and cholesterol
      levels at termination of the study, respectively, reached 126+/-81 and 164+/-71
      mg dl(-1), as compared to 333+/-108 and 378+/-26 mg dl(-1) on Day first (P <
      0.01). In the control group, these values on the fourth day were, respectively,
      267+/-94 and 263+/-79 vs. 247+/-115 and 315+/-78 on Day first (P > 0.05).
      CONCLUSIONS: Guar gum-enriched enteral nutrition was related to a decrease of
      diarrheal episodes in ICU patients with preexisting diarrhea; and to a trend for
      lower plasma glucose and cholesterol levels.

PMID- 15556257
TI  - Indicators of nutritional status in restricting-type anorexia nervosa patients: a
      1-year follow-up study.
AB  - BACKGROUND AND AIM: Despite severely reduced intakes, anorexia nervosa (AN)
      patients seem to maintain serum biochemical parameters within the safe limit. The
      aim of this study was to assess the evolution of some traditional serum
      biochemical indicators of nutritional status in a 1-year follow-up of patients
      with restricting-type AN. METHODS: 14 adolescent female patients were studied at
      four different time points: (1) on hospital admission (t0), (2) 1 month later
      (t1), (3) 6 months after admission (t6) and (4) 12 months after admission (t12).
      At each time point serum albumin, prealbumin, retinol-binding protein,
      transferrin, complement factors C3 and C4, zinc and iron status were analysed. 15
      healthy adolescents formed the control group. RESULTS: Among the liver
      synthesised proteins, a significant time effect was only demonstrated on
      transferrin and C3 and C4 (ANOVA, P<0.05). Transferrin level in patients on
      admission was lower than in controls, increased significantly during the first
      month and showed an opposite pattern in subjects gaining and non-gaining weight
      between t1 and t12, decreasing only in the group failing to gain further weight.
      C3 and C4 decreased significantly in t12. Changes in ferritin and zinc showed
      significant negative correlations with changes in anthropometrical parameters.
      CONCLUSIONS: The changes in transferrin, C3 and C4 levels during the out-patient
      treatment reveal an increased risk of relapses after 1 year since hospital
      admission. Ferritin and zinc levels seem to be affected by the nutrient
      requirements for anabolic processes during nutritional recovery.

PMID- 15556258
TI  - Pilot study on the effect of parenteral vitamin E on ischemia and reperfusion
      induced liver injury: a double blind, randomized, placebo-controlled trial.
AB  - BACKGROUND AND AIMS: Liver surgery usually involves ischemia and reperfusion
      (I/R) which results in oxidative stress and cell damage. The administration of
      antioxidants should diminish or prevent this damage. The purpose of this study
      was to investigate the effect of the antioxidant vitamin E on I/R injury.
      METHODS: We carried out a placebo-controlled double-blind study on 68 patients
      undergoing elective, tumor-related, partial liver resection. 47 patients were
      qualified for the per protocol population based evaluation. The patients were
      randomly assigned to two groups. The day before surgery one group received three
      infusions containing vitamin E (600 IU=540 mg vitamin E emulsion). The other
      group received three infusions of placebo. RESULTS: Length of stay in the
      intensive care unit (ICU) was significantly shorter in the verum group than in
      the placebo group (P<0.05). There were signs of improvement for AUC AST (P<0.05),
      ALT and GLDH in the verum group after surgery. Serum vitamin E concentration
      increased after administration of vitamin E infusion and declined in both
      treatment groups after surgery (P<0.01). In the verum group vitamin E deficiency
      was prevented while vitamin E concentration remained low in the placebo group
      (P<0.01). CONCLUSIONS: The findings from this study indicate that preoperative
      administration of vitamin E is safe and that this treatment may have beneficial
      effects by reducing the impact of I/R injury in liver surgery.

PMID- 15556259
TI  - Body composition in underweight elderly subjects: reliability of bioelectrical
      impedance analysis.
AB  - BACKGROUND AND AIMS: In underweight elderly subjects it is important to estimate
      body composition and particularly fat-free mass (FFM). Bioelectrical impedance
      analysis (BIA) is a non-invasive method in determining FFM, but its usefulness in
      these frail subjects should be verified. The aim of this study is to verify in
      underweight elderly people the reliability of previously published BIA formulas
      in detecting FFM. METHODS: Fifty-seven hospitalized elderly subjects (27 males
      and 30 females) with body mass index <20 kg/m(2) were selected. In all subjects,
      FFM was detected by dual energy X-ray absorptiometry. Moreover, BIA measurements
      were performed at standard frequency (50 kHz and 800 microA) and FFM was derived
      using the main previous published BIA equations. RESULTS: In men, Kyle and Rising
      equations gave acceptable estimates of FFM with a mean error, respectively, of
      1+/-1.9 and 1.4+/-1.7 kg. Also RJL formula could be used after adjusting for a
      correction factor. In women, no equation seemed sufficiently reliable to estimate
      FFM. CONCLUSIONS: BIA method seems useful to evaluate body composition in
      underweight elderly men but it seems to have intrinsic limits in women.
      Nevertheless, the variability in behavior of the different equations suggests to
      be careful in adopting BIA equations.

PMID- 15556260
TI  - The effect of cumulative energy and protein deficiency on anthropometric
      parameters in a pediatric ICU population.
AB  - BACKGROUND AND AIMS: Nutritional support is essential in the care of critically
      ill children since inadequate feeding increases morbidity and negatively affects
      growth. We aimed to compare cumulative energy and protein intakes with
      recommended dietary intakes (RDA) and examine relationships between accumulated
      balances and anthropometric parameters. METHODS: Prospective, observational
      study. Total daily energy and protein intakes were determined during a maximum of
      14 days in 261 children admitted to our multidisciplinary tertiary pediatric ICU.
      Actual intakes were subtracted from RDA and cumulative balances were calculated.
      Relations between cumulative balances, various clinical factors and changes in
      anthropometry (weight, arm and calf circumference) were analyzed using regression
      analysis. RESULTS: At 14 days after admission children showed significant
      cumulative nutritional deficits compared to RDA. These deficits were on average
      27, 20, 12 kcal/kg and 0.6, 0.3, and 0.2 g protein/kg per day for preterm
      neonates (n = 103), term neonates (n = 91) and older children (n = 67),
      respectively. Age at admission, length of ICU-stay and days on mechanical
      ventilation were negatively related to cumulative balances. Cumulative energy and
      protein deficits were associated with declines in SD-scores for weight and arm
      circumference. CONCLUSIONS: Children admitted to the ICU accumulate substantial
      energy and protein deficits when compared to RDA. These deficits are related to
      decreases in anthropometric parameters.

PMID- 15556261
TI  - Evaluation of lipid oxidation after ingestion of bakery products enriched with
      phytosterols, beta-carotene and alpha-tocopherol.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the effect of the
      consumption of croissants and magdalenas (Spanish muffins), enriched with sterol
      esters, alpha-tocopherol and beta-carotene, on plasma lipid peroxidation. TBA and
      conjugated dienes were used as markers of lipid peroxidation. METHODS: The study
      was made to a population without changes in their diet or lifestyle, and based on
      a randomized double-blind controlled repeated measures design. The sample size
      was 57. During 8 weeks, the subjects of the control group (29) received two daily
      pieces (standard croissant and muffin), whereas those of the experimental group
      (28) received the same products, but enriched with sterol-esters, alpha
      tocopherol and beta-carotene. RESULTS: The treatment has a positive effect on TBA
      value for control group and that given to experimental group has negative effect.
      The mean difference between two groups is 3.16 (P = 0.044). Also TBA was found to
      be significantly correlated with HDL-, LDL-cholesterol and alpha-tocopherol, both
      before and after treatment, but TBA was only significantly correlated with beta
      carotene before treatment. Finally, the effects on LDL-cholesterol, alpha
      tocopherol and TBA presented similar correlation matrices in the two groups, most
      correlation coefficients being significant at group level, in spite of the low
      sample sizes, revealing the association between treatment effects.

PMID- 15556262
TI  - Body mass index and albumin in the preoperative evaluation of cardiac surgery
      patients.
AB  - BACKGROUND AND AIMS: An increasing proportion of cardiac surgery is performed in
      the elderly where nutritional status is an important predictor of outcome. Our
      aim was to evaluate serum albumin concentration (S-albumin) and body mass index
      (BMI) as markers of malnutrition in relation to outcome measured as mortality and
      frequency of infections. PATIENTS AND METHODS: We studied 886 consecutive
      patients who underwent cardiac surgery with extra-corporeal circulation for valve
      procedures, coronary artery bypass grafting or a combination of those.
      Preoperative assessment included age, gender, BMI, smoking habits, diabetes, left
      ventricular function, S-albumin and C-reactive protein. Postoperative data was
      type of surgery, in-hospital stay, signs of infections and mortality. Risk
      factors for mortality were identified using the Cox proportional hazard model and
      risk factors for infections by using the logistic-regression model. RESULTS: The
      patients (age 67+/-9.5 years) were followed for 22+/-6 months. In an univariate
      analysis low BMI and low S-albumin increased relative hazard for death and risk
      for infection. In a multivariate analysis low BMI, but not S-albumin, increased
      relative hazard for death and low S-albumin, but not BMI, increased risk for
      infection. Age, diabetes and longer bypass time increased the risk for infection.
      CONCLUSION: In cardiac surgery patients a low BMI increased the relative hazard
      for death and low S-albumin increased the risk for infection. We suggest that
      these parameters provide useful information in the preoperative evaluation.

PMID- 15556263
TI  - Energy balance in cystic fibrosis when stable and during a respiratory
      exacerbation.
AB  - BACKGROUND AND AIMS: Undernutrition is common in young adult patients with cystic
      fibrosis (CF) and implies an imbalance between energy intake and total energy
      expenditure (TEE). The aim of this study was to measure energy intake and TEE
      expenditure in a group of patients when they were clinically stable at home and
      during an exacerbation of respiratory symptoms when they were in hospital
      receiving intravenous antibiotics. METHODS: Eleven patients aged between 15 and
      40 years with moderate respiratory disease, mean FEV(1) 51.4% predicted took
      part. An exacerbation was defined as>15% decrease in FEV(1), an increase in
      sputum production and a decision to treat in hospital with intravenous
      antibiotics. Resting energy expenditure (REE) was measured using indirect
      calorimetry and energy intake by 3 day food diaries. TEE expenditure was measured
      using 24 h heart rate and doubly isotopically labelled water. RESULTS: REE was
      higher at the beginning of an exacerbation than the end, P<0.05. There was no
      significant difference in TEE during the stable period compared to the
      exacerbation 10.53(2.39)MJ/day compared to 8.77(1.59)MJ/day using doubly
      isotopically labelled water. There was no difference in energy intake during the
      exacerbation compared to the stable period, 11.19(2.31)MJ/day compared to
      11.77(2.30)MJ/day. CONCLUSIONS: There was no difference in TEE and energy intake
      when patients were unwell in hospital compared to when they were stable at home
      despite an increase in REE.

PMID- 15556264
TI  - Myostatin expression is not altered by insulin deficiency and replacement in
      streptozotocin-diabetic rat skeletal muscles.
AB  - BACKGROUND AND AIMS: Insulin is a major post-prandial muscle-anabolic hormone. A
      substantial loss of skeletal muscle mass occurs in insulin-deprived diabetes and
      is reversed by insulin treatment. Myostatin is a negative regulator of muscle
      mass upregulated in several chronic catabolic conditions. Whether myostatin
      expression is altered in insulin-deprived diabetes is unknown. In spite of
      opposite effects on muscle mass the potential role of basal circulating insulin
      in the regulation of myostatin expression is also undetermined. METHODS: We
      measured (Northern Blot) myostatin transcript levels in muscle groups with
      different fiber composition in streptozotocin-diabetic male rats receiving one of
      the following treatments for eight weeks: (1) control (C); (2) diabetes without
      treatment (DM); (3) diabetes with once-daily slow-acting insulin treatment (INS).
      RESULTS: INS normalized plasma insulin and prevented weight reduction observed in
      DM. In fast-twitch gastrocnemius muscle myostatin transcript levels were
      unchanged (P>0.4) in both DM and INS compared to C. Myostatin transcripts were
      not measurable in any group in slow-twitch soleus muscle. CONCLUSIONS: Muscle
      specific myostatin expression is not increased under catabolic conditions in
      insulin-deprived diabetes. Insulin treatment also does not change myostatin
      transcript levels. The data provide the first assessment of potential interplay
      between insulin and myostatin and they do not support a major role of circulating
      insulin in the in vivo regulation of myostatin gene expression. A role of
      myostatin in muscle catabolism in chronic insulin-deprived diabetes is also not
      indicated by the current results.

PMID- 15556265
TI  - Potential usefulness of olive oil-based lipid emulsions in selected situations of
      home parenteral nutrition-associated liver disease.
AB  - Long-term (i.e. home) parenteral nutrition has been advocated to be responsible
      for several metabolic complications among which hepatic disorders have long been
      the most relevant in view of patients' prognosis. The increased knowledge of the
      pathophysiologic factors associated to parenteral nutrition-related liver disease
      as well as the regular improvement of the components and the techniques used for
      parenteral nutrition leaded progressively to a better prevention of these side
      effects. This case report focuses on the potential interest of olive oil-based
      lipid emulsions in home parenteral nutrition patients, in selected situations of
      home parenteral nutrition-associated metabolic liver disease.

PMID- 15556266
TI  - European round table: the use of immunonutrients in the critically ill.

PMID- 15556267
TI  - Bioelectrical impedance analysis-part II: utilization in clinical practice.
AB  - BIA is easy, non-invasive, relatively inexpensive and can be performed in almost
      any subject because it is portable. Part II of these ESPEN guidelines reports
      results for fat-free mass (FFM), body fat (BF), body cell mass (BCM), total body
      water (TBW), extracellular water (ECW) and intracellular water (ICW) from various
      studies in healthy and ill subjects. The data suggests that BIA works well in
      healthy subjects and in patients with stable water and electrolytes balance with
      a validated BIA equation that is appropriate with regard to age, sex and race.
      Clinical use of BIA in subjects at extremes of BMI ranges or with abnormal
      hydration cannot be recommended for routine assessment of patients until further
      validation has proven for BIA algorithm to be accurate in such conditions. Multi
      frequency- and segmental-BIA may have advantages over single-frequency BIA in
      these conditions, but further validation is necessary. Longitudinal follow-up of
      body composition by BIA is possible in subjects with BMI 16-34 kg/m(2) without
      abnormal hydration, but must be interpreted with caution. Further validation of
      BIA is necessary to understand the mechanisms for the changes observed in acute
      illness, altered fat/lean mass ratios, extreme heights and body shape
      abnormalities.

PMID- 15556268
TI  - Probing the origins, diagnosis and treatment of amyloid diseases using
      antibodies.
AB  - The deposition of proteins in the form of amyloid fibrils is the characteristic
      feature of more than 20 medical conditions affecting the central nervous system
      or a variety of peripheral tissues. These disorders, which include Alzheimer's
      disease, the prion diseases and type II diabetes, are of enormous importance in
      the context of present-day human health and welfare. Extensive research is
      therefore being carried out to define the molecular details of the mechanism of
      the pathological conversion of amyloidogenic proteins from their soluble forms
      into fibrillar structures. This review focuses on recent studies that demonstrate
      the power of using antibodies or antibody fragments to probe the process of
      fibril formation, and discusses the emerging potential of these species as
      diagnostic and therapeutic agents.

PMID- 15556269
TI  - High throughput cloning and expression strategies for protein production.
AB  - Traditionally, the production of a recombinant protein requires a preliminary
      cloning step of the target gene into an expression vector before evaluating its
      cellular expression. Among current methods, site-specific recombination cloning
      techniques, which eliminate the use of restriction endonucleases and ligase,
      offer several advantages in the context of high throughput (HT) procedures. Rapid
      and highly efficient, the recombinational cloning technology is largely used for
      structural genomics and functional proteomics. However, the correct expression of
      some genes requires further optimization steps that are time-consuming and
      carried out at relatively late stages in the cloning-expression process. An
      alternative strategy is described where expression is tested in vitro before
      cloning the target gene. This technology, amenable to automation for HT studies,
      makes the expression of several hundreds of genes possible from PCR products in
      cell-free transcription-translation systems. Once this preliminary step is
      achieved, the PCR product, which gives satisfying expression levels, is selected,
      and then cloned in a plasmid for its cellular expression and perpetuation.

PMID- 15556270
TI  - Peptidomic and proteomic analyses of the systemic immune response of Drosophila.
AB  - Insects have developed an efficient host defense against microorganisms, which
      involves humoral and cellular mechanisms. Numerous data highlight similarities
      between defense responses of insects and innate immunity of mammals. The fruit
      fly, Drosophila melanogaster, is a favorable model system for the analysis of the
      first line defense against microorganisms. Taking advantages of improvements in
      mass spectrometry (MS), two-dimensional (2D) gel electrophoresis and
      bioinformatics, differential analyses of blood content (hemolymph) from immune
      challenged versus control Drosophila were performed. Two strategies were
      developed: (i) peptidomic analyses through matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) MS and high performance liquid
      chromatography for molecules below 15 kDa, and (ii) proteomic studies based on 2D
      gel electrophoresis, MALDI-TOF fingerprinting and database searches, for
      compounds of greater molecular masses. The peptidomic strategy led to the
      detection of a large number of peptides induced in the hemolymph of challenged
      flies as compared to controls. Of these, 28 were characterized, amongst which
      were antimicrobial peptides. The 2D gel electrophoresis strategy led to the
      detection of 70 spots differentially regulated by at least fivefold after
      microbial infection. This approach yielded the identity of a series of proteins
      that were related to the Drosophila immune response, such as proteases, protease
      inhibitors, prophenoloxydase-activating enzymes, serpins and a Gram-negative
      binding protein-like protein. This strategy also brought to light new candidates
      with a potential function in the immune response (odorant-binding protein,
      peptidylglycine alpha-hydroxylating monooxygenase and transferrin).
      Interestingly, several molecules resulting from the cleavage of proteins were
      detected after a fungal infection. Together, peptidomic and proteomic analyses
      represent new tools to characterize molecules involved in the innate immune
      reactions of Drosophila.

PMID- 15556271
TI  - The Paris-Sud yeast structural genomics pilot-project: from structure to
      function.
AB  - We present here the outlines and results from our yeast structural genomics (YSG)
      pilot-project. A lab-scale platform for the systematic production and structure
      determination is presented. In order to validate this approach, 250 non-membrane
      proteins of unknown structure were targeted. Strategies and final statistics are
      evaluated. We finally discuss the opportunity of structural genomics programs to
      contribute to functional biochemical annotation.

PMID- 15556272
TI  - Integrating a functional proteomic approach into the target discovery process.
AB  - Functional proteomics is a promising technique for the rational identification of
      novel therapeutic targets by elucidation of the function of newly identified
      proteins in disease-relevant cellular pathways. Of the recently described high
      throughput approaches for analyzing protein-protein interactions, the yeast two
      hybrid (Y2H) system has turned out to be one of the most suitable for genome-wide
      analysis. However, this system presents a challenging technical problem: the high
      prevalence of false positives and false negatives in datasets due to intrinsic
      limitations of the technology and the use of a high-throughput, genetic assay. We
      discuss here the different experimental strategies applied to Y2H assays, their
      general limitations and advantages. We also address the issue of the contribution
      of protein interaction mapping to functional biology, especially when combined
      with complementary genomic and proteomic analyses. Finally, we illustrate how the
      combination of protein interaction maps with relevant functional assays can
      provide biological support to large-scale protein interaction datasets and
      contribute to the identification and validation of potential therapeutic targets.

PMID- 15556273
TI  - Decrease of human hepatoma cell growth by arachidonic acid is associated with an
      accumulation of derived products from lipid peroxidation.
AB  - We showed that the metabolism of arachidonic acid (AA) in HepG2 cells generates
      reactive oxygen species (ROS), which activate the p38 mitogen-activated protein
      kinase (MAPK) pathway and the redox-sensitive transcription factors AP-1 and NF
      kappaB, leading to the induction of the antioxidant manganese superoxide
      dismutase gene. The present study reports that AA decreases the HepG2 cell growth
      by 40% and 55% after a treatment for 24 and 48 h, respectively. This effect was
      blocked by an inhibitor of lipoxygenase/cytochrome P450 monooxygenase pathways
      and by the antioxidants. In addition, AA induced an oxidative stress, as an
      accumulation of malondialdehyde (MDA)-modified proteins, resulting to a
      generation of MDA and H(2)O(2) was observed after 24 h. This AA-induced oxidative
      stress was associated with the lack of an increase in the H(2)O(2)-degrading
      enzyme level. In contrast, 5,8,11,14-eicosatetraynoic acid, a nonmetabolizable
      analog of AA, had not effect. The peroxisome proliferator-activated receptor
      gamma (PPARgamma) with AA metabolites as ligands was upregulated by the fatty
      acid but was not involved in the AA effect because its transcriptional activity
      estimated by reporter gene assays was negatively controlled by p38 MAPK pathway.
      These findings suggest that the effect of AA on human hepatoma cell growth by
      inducing an oxidative stress may present a clinical interest in the treatment of
      the liver cancer.

PMID- 15556274
TI  - Boophilus microplus tick larvae, a rich source of Kunitz type serine proteinase
      inhibitors.
AB  - Serine proteinase inhibitors from Boophilus microplus tick larvae (BmTIs) were
      purified by affinity chromatography on a trypsin-Sepharose column. BmTIs
      presented molecular weight between M(r) 6200 and 18,400 and inhibitory activity
      for trypsin, HuPK (human plasma kallikrein) and neutrophil elastase. Using ion
      exchange chromatography, BmTIs were separated in several protein pools named BmTI
      A to BmTI-F and BmTI-1 to BmTI-7. All BmTI forms presented inhibitory activity
      for trypsin with apparent dissociation constants (K(i)) in the nM range. In this
      work, we describe the purification of BmTI-D, BmTI-2, and BmTI-3. These three
      inhibitors affected neutrophil elastase and HuPK with K(i) also in nM range. BmTI
      D proved to be the best HuPK inhibitor, while BmTI-3 was more efficient for
      neutrophil elastase with dissociation constants (K(i)) of 12 and 0.5 nM,
      respectively. BmTI-D, BmTI-2, and BmTI-3 N-terminal amino acid sequences allowed
      us to include them into the BPTI-Kunitz type serine proteinase inhibitor family.
      BmTIs purified on trypsin-Sepharose were also used in a bovine immunization
      assay, resulting in antibody (anti-BmTIs) production.

PMID- 15556275
TI  - Enhancement of lysozyme stability and activity by polyamines.
AB  - Spermine, a low molecular weight polyamine, administered orally to suckling rats
      induces the maturation of the small intestine. In this organ, lysozyme is an
      important component of the innate immunity. In this report, we analysed the
      binding of spermine to lysozyme and its effect on thermal inactivation of the
      protein by spectroscopy techniques. The activity of the enzyme was analysed in
      presence of spermine by lysoplate technique. We studied the effects of spermine
      ingestion by suckling rats on intestinal lysozyme activity and gene expression.
      We reported that spermine binds to lysozyme and increases in vitro the thermal
      stability and the activity of the protein. When administered orally to suckling
      rats, spermine increases the lysozyme activity in jejunum, but not in ileum. This
      increase is not due to a modification of the gene expression. The observed
      effects lead us to postulate that spermine could be used in some mammals as a
      promoter of the innate immunity.

PMID- 15556276
TI  - A biologically active lectin of enteroaggregative Escherichia coli.
AB  - The pathogenesis of enteroaggregative Escherichia coli, a major contributor to
      paediatric diarrhoea, is still not clearly understood. A complex carbohydrate
      specific lectin was identified from the culture supernatant of an
      enteroaggregative E. coli strain. The lectin was purified to 660-fold by a
      combination of sequential saturated ammonium sulphate precipitation and gel
      filtration chromatography in the FPLC system. The homogeneity of the purified
      lectin was established by analytical isoelectrofocusing [pI 6.75].
      Hemagglutination of rabbit erythrocytes by the purified lectin was best inhibited
      by fetuin. The N-terminal sequence of the 41.7 kDa subunit showed homology to the
      outermembrane porins and the 23.4 kDa subunit showed homology to a hypothetical
      protein of Yersinia pestis and secreted Hcp protein. This protein could induce
      extensive morphological changes in HEp-2 cells and significant amount of fluid
      accumulation in rabbit ileal loop. GM1 showed maximum binding to the lectin among
      all other gangliosides. This purified protein showed cross-reactivity to the
      binding subunit of cholera toxin in western immunoblot. The presence of this
      toxin in some of the clinical isolates of enteroaggregative E. coli was also
      observed. The structural and functional characteristics of the toxin revealed
      that it is a novel virulence determinant of aggregative E. coli.

PMID- 15556277
TI  - Kinetic study of the effects of calcium ions on cationic artichoke (Cynara
      scolymus L.) peroxidase: calcium binding, steady-state kinetics and reactions
      with hydrogen peroxide.
AB  - The apparent catalytic constant (k(cat)) of artichoke (Cynara scolymus L.)
      peroxidase (AKPC) with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)
      (ABTS) increased 130-fold in the presence of calcium ions (Ca2+) but the affinity
      (K(m)) of the enzyme for ABTS was 500 times lower than for Ca2+-free AKPC. AKPC
      is known to exhibit an equilibrium between 6-aquo hexa-coordinate and penta
      coordinate forms of the haem iron that is modulated by Ca2+ and affects compound
      I formation. Measurements of the Ca2+ dissociation constant (K(D)) were
      complicated by the water-association/dissociation equilibrium yielding a global
      value more than 1000 times too high. The value for the Ca2+ binding step alone
      has now been determined to be K(D) approximately 10 nM. AKPC-Ca2+ was more
      resistant to inactivation by hydrogen peroxide (H(2)O(2)) and exhibited increased
      catalase activity. An analysis of the complex H(2)O(2) concentration dependent
      kinetics of Ca2+-free AKPC is presented.

PMID- 15556278
TI  - Structural composition and differential anticoagulant activities of dermatan
      sulfates from the skin of four species of rays, Dasyatis americana, Dasyatis
      gutatta, Aetobatus narinari and Potamotrygon motoro.
AB  - We compared the disaccharide composition of dermatan sulfate (DS) purified from
      the ventral skin of three species of rays from the Brazilian seacoast, Dasyatis
      americana, Dasyatis gutatta, Aetobatus narinari and of Potamotrygon motoro, a
      fresh water species that habits the Amazon River. DS obtained from the four
      species were composed of non-sulfated, mono-sulfated disaccharides bearing
      esterified sulfate groups at positions C-4 or C-6 of N-acetyl galactosamine
      (GalNAc), and disulfated disaccharides bearing esterified sulfate groups at
      positions C-2 of the uronic acid and at position C-4 or C-6 of GalNAc. However,
      DS from the skin of P. motoro presented a very low content of the disulfated
      disaccharides. The anticoagulant actions of ray skin DS, measured by both APTT
      clotting and HCII-mediated inhibition of thrombin assays, were compared to that
      of mammalian DS. DS from D. americana had both high APTT and HCII activities,
      whereas DS from D. gutatta showed activity profiles similar to those of mammalian
      DS. In contrast, DS from both A. narinari and P. motoro had no measurable
      activity in the APTT assay. Thus, the anticoagulant activity of ray skin DS is
      not merely a consequence of their charge density. We speculate that the
      differences among the anticoagulant activities of these three DS may be related
      to both different composition and arrangements of the disulfated disaccharide
      units within their polysaccharide chains.

PMID- 15556279
TI  - Artocarpin is a polyspecific jacalin-related lectin with a monosaccharide
      preference for mannose.
AB  - A reinvestigation of the carbohydrate-binding properties revealed that
      artocarpin, a previously described mannose-specific lectin from jackfruit
      (Artocarpus integrifolia) seeds, behaves as a polyspecific lectin. Surface
      plasmon resonance hapten inhibition experiments demonstrated that artocarpin
      readily interacted with a wide range of monosaccharides covering galactose, N
      acetylgalactosamine, mannose, glucose, sialic acid and N-acetylmuramic acid.
      Molecular docking confirmed this unexpected ability of artocarpin to interact
      with structurally different sugars. The biological significance of the
      polyspecificity of the lectin is discussed in terms of the broadening of the
      range of potential target glycans present on the surface of plant phytopathogens
      or predators.

PMID- 15556280
TI  - Comparison of physico-chemical characteristics of four laccases from different
      basidiomycetes.
AB  - New strains of basidiomycetes producing extracellular laccases (Trametes ochracea
      92-78, and Trametes hirsuta 56) have been found by screening of isolates of
      Trametes fungi. The laccases from T. hirsuta 56 and T. ochracea 92-78 as well as
      two laccases from previously found and described strains of basidiomycetes,
      namely Cerrena maxima and Coriolopsis fulvocinerea, were purified to homogeneity.
      The standard redox potentials of type 1 copper in the enzymes were determined and
      found to be 780, 790, 750, and 780 mV, respectively. The spectral and biochemical
      studies showed that the enzymes had no significant differences between the
      structures of their active sites (T1, T2, and T3). In spite of this fact, the
      basic biochemical properties as well as the redox potentials of the T1 sites of
      the enzymes were found to be different. The molecular weights of the laccases
      range from 64 to 70 kDa, and their pI values range from 3.5 to 4.7. The pH-optima
      are in the range 3.5-5.2. The temperature optimum for activity is about 50
      degrees C. The thermal stabilities of the enzymes were studied. The catalytic and
      Michaelis constants for catechol, guaiacol, hydroquinone, sinapinic acid, and
      K(4)Fe(CN)(6) were determined. Based on these results as well as results obtained
      by comparing with published properties of several laccases, it could be concluded
      that T. hirsuta and Cerrena maxima laccases have some superior characteristics
      such as high stability, high activity, and low carbohydrate content, making them
      attractive objects for further investigations as well as for application in
      different areas of biotechnology.

PMID- 15556281
TI  - Kinetic properties of native and mutagenized isoforms of mitochondrial alcohol
      dehydrogenase III purified from Kluyveromyces lactis.
AB  - By computer modelling and protein engineering we have investigated changes in two
      amino acid residues located in the coenzyme pocket of the yeast Kluyveromyces
      lactis mitochondrial alcohol dehydrogenase III. These two residues, Gly 225 and
      Ala 274, were hypothesized to be involved in the enzyme discrimination between
      NAD(H) and NADP(H). Upon changing Gly 225 to Ala we produced an enzyme (mutant
      G225A) showing very little difference from the wild-type. On the contrary, change
      at position 274 of Phe instead of Ala (mutant A274F) caused a significant
      increase of K(m) values for NAD(P) and for NADPH and even a more marked decrease
      in catalytic activity. The k(cat)/K(m) rates for NADP(H) were also decreased in
      this mutant. Enzymes with the double changes at 225 and 274 (mutant G225A-A274F)
      showed, apart the substantial low K(m) value for NADPH and its high catalytic
      efficiency, kinetic parameters relative to coenzymes which were not additive over
      the single substitutions. Surprisingly, enzymes with changes at the two positions
      reduced efficiently acetaldehyde, displaying a K(m) value 10-fold lower and a
      catalytic efficiency sevenfold higher with respect to parent or singularly
      mutated enzymes. None of the engineered enzymes would convert formaldehyde,
      glutaraldehyde or aromatic aldehydes but all enzymes reduced propionaldehyde and
      butyraldehyde at relative reaction rates approximately half of that exhibited by
      acetaldehyde. Interestingly only mutant A274F was able to oxidize methanol almost
      as well as ethanol. In addition, this mutant was capable to convert secondary and
      cyclic alcohols, at a rate not detected in the other isoforms. These results are
      in general agreement with the prediction that increasing the size of amino acids
      in the proximity of the coenzyme pocket would hamper the accommodation of NADP
      but discord the increased affinity for NADPH as well as for alcoholic or
      aldehydic substrates with high steric hindrance.

PMID- 15556282
TI  - Discrimination of target by siRNA: designing of AML1-MTG8 fusion mRNA-specific
      siRNA sequences.
AB  - AML1-MTG8 is a chimeric transcription factor produced by t(8;21) chromosome
      translocation and causes AML. AML1-MTG8 acts as a dominant negative effector on
      normal AML1 protein, a key transcriptional regulator of hematopoietic
      differentiation, but its precise mechanism is not known. To analyze the function
      of AML1-MTG8 in leukemic cells and to explore the possibility of AML1-MTG8
      targeted therapy, we designed nine small interfering RNAs (siRNAs) targeting a 25
      nucleotide region spanning the fusion point of AML1 and MTG8. Two different
      siRNAs (AM2 and AM4) significantly reduced AML1-MTG8 expression from a
      transfected reporter plasmid at both the mRNA and protein levels. Both siRNAs did
      not reduce AML1b expression, but AM2 siRNA showed slightly reducing activity
      against MTG8b mRNA that is 86% homologous to the corresponded region of AML1-MTG8
      mRNA. Moreover, using a cationic lipid reagent, the siRNAs were efficiently
      introduced into leukemia cell lines with t(8;21), SKNO-1 (30-40%) and Kasumi-1
      (60-70%) cells, and reduced specifically the endogenous AML1-MTG8 expression. The
      siRNAs reduced neither the wild type AML1 in Kasumi-1 cells nor wild type MTG8b
      in human erythroblastic leukemia (HEL) cells. These results indicated that the
      two siRNAs are highly specific for the fusion mRNA. The knockdown of AML1-MTG8 in
      Kasumi-1 cells resulted in the activation of p14(ARF) promoter activity and
      increased the expression of integrin alphaIIb, whose expression is related to
      megakaryocytic differentiation. However, the knockdown of AML1-MTG8 in Kasumi-1
      cells did not inhibit the cell growth, suggesting that the siRNA-mediated
      knockdown of AML1-MTG8 is useful for the functional analysis of the gene, but it
      alone might not be sufficient for gene therapy of the leukemia.

PMID- 15556283
TI  - Affinity labeling of a catalytic site, cysteine(247), in rat mercaptopyruvate
      sulfurtransferase by chloropyruvate as an analog of a substrate.
AB  - A bisubstrate enzyme, rat mercaptopyruvate sulfurtransferase (EC 2.8.1.2), is
      inactivated by 3-chloropyruvate, an analog of 3-mercaptopyruvate serving as a
      sulfur-donor and -acceptor substrate. To elucidate a reaction mechanism of the
      enzyme, the inactivation kinetic studies using 3-chloropyruvate were carried out.
      However, 3-chloropyruvate cannot be mixed with 3-mercaptopyruvate, 2
      mercaptoethanol and thiosulfate because these substrates decompose 3
      chloropyruvate. Thus, 3-mercaptopyruvate sulfurtransferase was incubated with 3
      chloropyruvate, and then the remaining activity was measured separately in the
      assay system containing 3-mercaptopyruvate and 2-mercaptoethanol. The
      inactivation kinetics was analyzed by Kitz and Wilson method (J. Biol. Chem. 237
      (1962) 3245-3248). The inactivation of mercaptopyruvate sulfurtransferase by 3
      chloropyruvate proceeded in one-on-one manner and exhibited pseudo first-order
      kinetics with k(inact) = 0.068 +/- 0.003 min(-1) and K(I) = 4.0 +/- 0.2 mM (n =
      3, mean +/- S.D.). Further, SH titration using DTNB revealed that MST was
      inactivated by 3-chloropyruvate in a 1:1 stoichiometry. Site-directed mutagenesis
      for binding sites of 3-mercaptopyruvate (Arg(187)-->Gly or Arg(196)-->Gly) (J.
      Biol. Chem. 271 (1996) 27395-27401) did not critically affect the inactivation.
      These findings suggest that 3-chloropyruvate behaves as an affinity label and
      directly tags the catalytic site, Cys(247). An ESI-LC/Q-TOF mass spectrometric
      study suggests that a pyruvate adduct is formed at Cys(247), which mimics a
      reaction intermediate.

PMID- 15556284
TI  - Signal transduction pathways involved in the platelet aggregation induced by a D
      49 phospholipase A2 isolated from Bothrops jararacussu snake venom.
AB  - Bothropstoxin-II (Bthtx-II), an Asp-49 phospholipase A(2) (D-PLA(2)) isolated
      from Bothrops jararacussu snake venom is able to induce platelet aggregation in a
      concentration-dependent manner. This effect was not due to the release of ADP
      from platelets since the aggregation was not suppressed by ADP scavenger systems.
      PMSF and PPACK were unable to inhibit Bthtx-II-induced platelet aggregation.
      Thus, a thrombin-like proaggregating activity of Bthtx-II can be excluded as its
      mechanism of action. On the other hand, indomethacin at low concentrations
      inhibited more markedly the ATP-release reaction than the aggregation induced by
      Bthtx-II, indicating that generation of cyclooxigenase products is not the most
      important event for the platelet aggregation reaction. It was also found that
      staurosporine and genistein suppressed both platelet aggregation and ATP-release
      reactions, but not the platelet shape-change induced by Bthtx-II. Substances that
      either directly activates adenylyl cyclase enzyme (forskolin and PGE(1)) or cell
      permeant increasing agents (dibutyril-cAMP) inhibited in a concentration
      dependent fashion, the platelet aggregation effects induced by the protein. It is
      concluded that Bthtx-II induces platelet aggregation and secretion through
      multiple signal transduction pathways.

PMID- 15556285
TI  - The supramammillary area: its organization, functions and relationship to the
      hippocampus.
AB  - The supramammillary area of the hypothalamus, although small in size, can have
      profound modulatory effects on the hippocampal formation and related temporal
      cortex. It can control hippocampal plasticity and also has recently been shown to
      contain cells that determine the frequency of hippocampal rhythmical slow
      activity (theta rhythm). We review here its organization and anatomical
      connections providing an atlas and a new nomenclature. We then review its
      functions particularly in relation to its links with the hippocampus. Much of its
      control of behaviour and its differential activation by specific classes of
      stimuli is consistent with a tight relationship with the hippocampus. However,
      its ascending connections involve not only caudal areas of the cortex with close
      links to the hippocampus but also reciprocal connections with more rostral areas
      such as the infralimbic and anterior cingulate cortices. These latter areas
      appear to be the most rostral part of a network that, via the medial septum,
      hippocampus and lateral septum, is topographically mapped into the hypothalamus.
      The supramammillary area is thus diffusely connected with areas that control
      emotion and cognition and receives more topographically specific return
      information from areas that control cognition while also receiving ascending
      information from brain stem areas involved in emotion. We suggest that it is a
      key part of a network that recursively transforms information to achieve
      integration of cognitive and emotional aspects of goal-directed behaviour.

PMID- 15556286
TI  - Norepinephrine and acetylcholine mediation of the components of reflexive
      attention: implications for attention deficit disorders.
AB  - Attention deficit hyperactivity disorders (ADHD) create major learning barriers
      for children and significant social and legal handicaps for adults worldwide.
      Important advances in the genetic basis of the disease have been made, but
      reliable, biological, diagnostic markers remain elusive. This review takes the
      position that future progress in treating the core symptom of attention deficits
      requires a clearer understanding of the neuroscience of attention in normal
      individuals. Two important achievements in this direction have been the
      development of tasks that identify activity in the orienting, alerting and
      conflict networks, and the identification of neurotransmitters that mediate these
      components. The proven ability of these tasks to identify and characterize
      response components of "normal" attention argues that they could be used
      advantageously with patient populations. The categorization of neurotransmitter
      abnormalities in those with ADHD could clarify whether attention deficits occur
      within or across attention networks. To realize these goals, we evaluate
      laboratory studies of attention in humans and animals that address the underlying
      neurotransmitter systems, primarily norepinephrine and acetylcholine. We propose
      that key facts about deficits in reflexive and voluntary attention may be
      understood by a model that includes deficits in brain norepinephrine release and
      its effects on cholinergic activity in the parietal cortex.

PMID- 15556287
TI  - A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox
      24/TIS8/ZENK?
AB  - Zif268 is a transcription regulatory protein, the product of an immediate early
      gene. Zif268 was originally described as inducible in cell cultures; however, it
      was later shown to be activated by a variety of stimuli, including ongoing
      synaptic activity in the adult brain. Recently, mice with experimentally mutated
      zif268 gene have been obtained and employed in neurobiological research. In this
      review we present a critical overview of Zif268 expression patterns in the naive
      brain and following neuronal stimulation as well as functional data with Zif268
      mutants. In conclusion, we suggest that Zif268 expression and function should be
      considered in a context of neuronal activity that is tightly linked to neuronal
      plasticity.

PMID- 15556288
TI  - Dynamics of sensory thalamocortical synaptic networks during information
      processing states.
AB  - The thalamocortical network consists of the pathways that interconnect the
      thalamus and neocortex, including thalamic sensory afferents, corticothalamic and
      thalamocortical pathways. These pathways are essential to acquire, analyze, store
      and retrieve sensory information. However, sensory information processing mostly
      occurs during behavioral arousal, when activity in thalamus and neocortex
      consists of an electrographic sign of low amplitude fast activity, known as
      activation, which is caused by several neuromodulator systems that project to the
      thalamocortical network. Logically, in order to understand how the
      thalamocortical network processes sensory information it is essential to study
      its response properties during states of activation. This paper reviews the
      temporal and spatial response properties of synaptic pathways in the whisker
      thalamocortical network of rodents during activated states as compared to
      quiescent (non-activated) states. The evidence shows that these pathways are
      differentially regulated via the effects of neuromodulators as behavioral
      contingencies demand. Thus, during activated states, the temporal and spatial
      response properties of pathways in the thalamocortical network are transformed to
      allow the processing of sensory information.

PMID- 15556289
TI  - Genetic and epigenetic modulation of telomerase activity in development and
      disease.
AB  - Telomerase activity is one of the most important factors that have been linked to
      multiple developmental processes, including cell proliferation, differentiation,
      aging and senescence. Dysregulation of telomerase has often been found in
      developmental abnormalities, such as cancer, loss of function in the
      hematopoietic system, and low success rate of somatic cloning. A comprehensive
      network of transcription factors has been shown to be involved in the genetic
      control of telomerase expression and activity. Epigenetic mechanisms have
      recently been shown to provide an additional level of regulation, and may be
      responsible for the diverse expression status of telomerase that is manifested in
      a tissue and cell-type-dependent manner. This article summarizes the recent
      developments in the field of telomerase research with a focus on the coregulation
      of the telomerase gene by both genetic and epigenetic pathways. Developmental
      consequences of aberrant telomerase activity will also be summarized and
      discussed.

PMID- 15556290
TI  - Bacterial expression system with tightly regulated gene expression and plasmid
      copy number.
AB  - A new Escherichia coli host/vector system has been engineered to allow tight and
      uniform modulation of gene expression and gamma origin (ori) plasmid copy number.
      Regulation of gamma ori plasmid copy number is achieved through arabinose
      inducible expression of the necessary Rep protein, pi, whose gene was integrated
      into the chromosome of the host strain under control of the P(BAD) promoter.
      gamma ori replication can be uniformly modulated over 100-fold by changing the
      concentration of l-arabinose in the growth medium. This strain avoids the problem
      of all-or-nothing induction of P(BAD) because it is deficient in both arabinose
      uptake and degradation genes. Arabinose enters the cell by a mutant LacY
      transporter, LacYA177C, which is expressed from the host chromosome. Although
      this strain could be compatible with any gamma ori plasmid, we describe the
      utility of a gamma ori expression vector that allows especially tight regulation
      of gene expression. With this host/vector system, it is possible to independently
      modulate gene expression and gene dosage, facilitating the cloning and
      overproduction of toxic gene products. We describe the successful use of this
      system for cloning a highly potent toxin, Colicin E3, in the absence of its
      cognate immunity protein. This system could be useful for cloning genes encoding
      other potent toxins, screening libraries for potential toxins, and maintaining
      any gamma ori vector at precise copy levels in a cell.

PMID- 15556291
TI  - Isolation and molecular characterization of the porcine stearoyl-CoA desaturase
      gene.
AB  - Stearoyl-CoA desaturase (SCD) is a rate-limiting enzyme in the biosynthesis of
      unsaturated fatty acids. So far only a partial porcine SCD sequence is available.
      Here we described the isolation and molecular characterization of the full-length
      cDNA and the determination of the genomic DNA sequence of the porcine SCD gene.
      The 5134-bp cDNA contains a 1080-bp open reading frame (ORF) encoding a protein
      of 359 amino acids with a calculated molecular mass of 41.3 kDa and a theoretical
      isoelectric point of 9.4. The porcine SCD protein shares high identity (>80%)
      with the other mammalian SCD. To further elucidate the genomic structure of the
      porcine SCD gene, we sequenced 20,985 bp of genomic DNA sequence encompassing the
      complete pig SCD gene. Similar to the other mammalian orthologs, particularly in
      term of exon size and exon/intron boundaries, the porcine SCD gene spans a
      transcription unit of 16,186 bp, consisting of six exons with sizes ranging from
      131 to 4048 bp, and five introns varying in size from 518 to 4784 bp. The gene
      reveals a 176-bp-long 5' UTR and possesses an unusually long 3'UTR of 3848 bp in
      the last exon. Comparison of different mammalian SCD promoters identified some
      regulatory domains required for the transcription regulation in the 5' flanking
      sequence of the porcine SCD gene, such as the conserved polyunsaturated fatty
      acid response region (PUFA-RE). A total of 21 gene polymorphisms were revealed in
      the 21-kb DNA sequence, including 19 single nucleotide polymorphisms (SNPs), a 24
      bp-long fragment length polymorphism in the fourth intron and a triplet
      nucleotide insertion in the fifth intron. Reverse transcription (RT)-PCR result
      indicates that the SCD gene is expressed ubiquitously in pigs.

PMID- 15556292
TI  - Identification and characterization of a novel gene family YPEL in a wide
      spectrum of eukaryotic species.
AB  - During comprehensive sequence analysis of human chromosome 22, we identified a
      novel gene family consisting of five members (YPEL1 through YPEL5) which has high
      homology with Drosophila yippee gene. We cloned and sequenced cDNAs for all five
      genes and determined their exon/intron organization. These YPEL genes showed high
      homology (43.8-96.6%) at amino acid sequence level among them. Mouse counterparts
      (Ypel1 through Ypel5) were also identified in the syntenic region of mouse
      chromosomes and their cDNAs were cloned and sequenced. Each of five pairs of
      human/mouse orthologs revealed extremely high homology. Thus, we named these
      genes as members of YPEL gene family. We searched YPEL family genes from the
      public databases, and found 100 genes from 68 species including animals, plants
      and fungi. Amino acid sequences of these 100 YPEL proteins were extremely similar
      and a consensus sequence of C-X(2)-C-X(19)-G-X(3)-L-X(5)-N-X(13)-G-X(8)-C-X(2)-C
      X(4)-GWXY-X(10)-K-X(6)-E was established for all the YPEL family proteins without
      exception. Interestingly, the indirect immunofluorescent staining indicated that
      YPEL1-4 proteins are localized to the centrosome and nucleolus during interphase
      and at several dot-like structures around the mitotic apparatus during mitotic
      phase of COS-7 cells. YPEL5 protein is localized to the centrosome and nucleus
      during interphase and at the mitotic spindle during mitosis of the same cell
      line. Thus, the YPEL family proteins were found in essentially all the eukaryotes
      and hence they must play important roles in the maintenance of life. The
      subcellular localization of YPEL proteins in association with centrosome or
      mitotic spindle suggests a novel function involved in the cell division.

PMID- 15556293
TI  - Genometric analyses of the organization of circular chromosomes: a universal
      pressure determines the direction of ribosomal RNA genes transcription relative
      to chromosome replication.
AB  - Selective pressures related to gene function and chromosomal architecture are
      acting on genome sequences and can be revealed, for instance, by appropriate
      genometric methods. Cumulative nucleotide skew analyses, i.e., GC, TA, and ORF
      orientation skews, predict the location of the origin of DNA replication for 88
      out of 100 completely sequenced bacterial chromosomes. These methods appear fully
      reliable for proteobacteria, Gram-positives, and spirochetes as well as for
      euryarchaeotes. Based on this genome architecture information, coorientation
      analyses reveal that in prokaryotes, ribosomal RNA (rRNA) genes encoding the
      small and large ribosomal subunits are all transcribed in the same direction as
      DNA replication; that is, they are located along the leading strand. This result
      offers a simple and reliable method for circumscribing the region containing the
      origin of the DNA replication and reveals a strong selective pressure acting on
      the orientation of rRNA genes similar to the weaker one acting on the orientation
      of ORFs. Rate of coorientation of transfer RNA (tRNA) genes with DNA replication
      appears to be taxon-specific. Analyzing nucleotide biases such as GC and TA skews
      of genes and plotting one against the other reveals a taxonomic clusterization of
      species. All ribosomal RNA genes are enriched in Gs and depleted in Cs, the only
      so far known exception being the rRNA genes of deuterostomian mitochondria.
      However, this exception can be explained by the fact that in the chromosome of
      the human mitochondrion, the model of the deuterostomian organelle genome, DNA
      replication, and rRNA transcription proceed in opposite directions. A general
      rule is deduced from prokaryotic and mitochondrial genomes: ribosomal RNA genes
      that are transcribed in the same direction as the DNA replication are enriched in
      Gs, and those transcribed in the opposite direction are depleted in Gs.

PMID- 15556294
TI  - MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated
      with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines.
AB  - In the search for novel genes involved in the taxol resistance phenotype, prior
      studies of gene expression in taxol-resistant cell lines and their paired drug
      sensitive parental lines using high-density Affymetrix microarrays identified
      MGC4175 as an overexpressed transcript. In this report, we characterize MGC4175
      and demonstrate that seven of eight taxol- and doxorubicin-resistant cell lines
      overexpressed MGC4175 as compared to their chemotherapy naive parent lines.
      Sequence analyses of MGC4175 cDNA and the predicted amino acid sequence did not
      show significant homology to any known sequence or protein domain, with an open
      reading frame of 356 bp that is predicted to encode a protein product of 118
      amino acids. Both the MGC4175 and MDR1 genes are located at chromosome position
      7q21. Southern blot analysis demonstrated that a single copy of MGC4175 is
      present in the human genome, and MGC4175 overexpression is not caused by genomic
      amplification or gene arrangement. Human MGC4175 fused to the carboxy terminus of
      enhanced green fluorescent protein (EGFP) and expressed in U-2OS cells localized
      the protein to the perinuclear region with further studies colocalizing this
      protein to the mitochondria. The Cancer Profiling Arrays and the Cancer Cell Line
      Profiling Array demonstrated that MGC4175 is broadly expressed in various tissues
      with no significant difference of MGC4175 expression between chemotherapy naive
      tumor cells and normal cells. However, MGC4175 is overexpressed 1.2- to 12.3-fold
      after 48 h of taxol induction and 0.65- to 6.5-fold after doxorubicin induction
      in various human cancer cell lines. In light of the overexpression of MGC4175 in
      association with taxol exposure, drug resistance, the coexpression of MDR1 and
      the mitochondrial localization of its protein, we propose to name this transcript
      MDR1 and Mitochondrial Taxol Resistance Associated Gene (MM-TRAG) and suggest
      that MM-TRAG may play a role in the development of taxol resistance in human
      cancer.

PMID- 15556295
TI  - Molecular cloning and characterization of a novel human BTB domain-containing
      gene, BTBD10, which is down-regulated in glioma.
AB  - The broad-complex, tramtrack (ttk) and bric-a-brac/poxvirus and zinc finger
      proteins (BTB/POZ) domain is highly conserved in a large family of eukaryotic
      proteins and is crucial for the latter's diverse roles in mediating interactions
      among proteins that are involved in transcription regulation and chromatin
      structures. From a fetal brain cDNA library, we isolated a cDNA of 2489 base
      pairs (bp) encoding a novel human BTB domain-containing protein named BTBD10. The
      cDNA contained an open-reading frame (ORF) of 1428 bp encoding a putative 475
      amino acid (aa) protein. The BTBD10 gene was located on human chromosome 11p15.2
      and consisted of nine exons spanning about 75.2 kilobase pairs (kb) of the human
      genome. The cDNA microarray analysis showed that BTBD10 was down-regulated in all
      18 glioma samples. The expression pattern of BTBD10 gene was examined by multiple
      tissue cDNA (MTC) panels (Clontech), which showed a ubiquitous expression pattern
      in the 16 tissues examined with high expression in adult brain, testis and small
      intestine and weak expression in the heart, lung, liver, kidney, pancreas,
      spleen, thymus, prostate, ovary and colon. The subcellular localization result
      revealed that BTBD10 was located specifically in the nucleus of HEK293 and COS7
      cell lines, suggesting that it may function in transcriptional regulation. The
      different expression patterns of BTBD10 in different grades of glioma versus
      normal brain were also examined by RT-PCR and Northern blot. We also investigated
      the expression of BTBD10 in hepatocellular carcinoma, ovary cancer and lung
      cancer, and the results revealed no significant difference in these three tumors.
      All these data suggested that BTBD10 might play a role in glioma.

PMID- 15556296
TI  - ZEC, a zinc finger protein with novel binding specificity and transcription
      regulatory activity.
AB  - A novel 114-kDa zinc finger protein, ZEC, has been found by cDNA cloning and
      characterized. ZEC was strongly expressed in the testis, liver and kidney, and
      also in embryonic stem cells. Epitope-tagged experiments indicated nuclear
      localization of ZEC. ZEC contained 18 C2H2 zinc fingers which were organized in
      two clusters. A ZEC binding DNA sequence, C/GA/TA/TGGTTGGTTGC, which we have
      designated the GT box, was identified by random oligonucleotide binding selection
      assay. The GT box did not contain binding sites for other previously
      characterized transcription factors and thus represented a potentially novel DNA
      target sequence. Electrophoretic mobility shift assay (EMSA) showed that both
      clusters of zinc fingers bound to the same DNA sequence. Site-directed
      mutagenesis revealed that the core sequence TTGGTT within the GT box was
      essential to ZEC binding, while DNA sequences outside of the core sequence
      enhanced this interaction. Furthermore, co-transfection assays demonstrated that
      ZEC could activate a reporter luciferase gene driven by this DNA sequence.

PMID- 15556297
TI  - A novel nucleolar protein, PAPA-1, induces growth arrest as a result of cell
      cycle arrest at the G1 phase.
AB  - We have identified a novel nucleolar protein, PAP-1-associated protein-1 (PAPA
      1), after screening the interacting proteins with Pim-1-associated protein-1 (PAP
      1), a protein that is a phosphorylation target of Pim-1 kinase. PAPA-1 comprises
      345 amino acids with a basic amino-acid cluster. PAPA-1 was found to be localized
      in the nucleolus in transfected HeLa cells, and the lysine/histidine cluster was
      essential for nucleolar localization of PAPA-1. PAPA-1 protein and mRNA
      expression decreased upon serum restimulation of starvation-synchronized cells,
      which displayed maximum level of PAPA-1 expression at G0 and early G1 phase of
      the cell cycle. Ectopic expression of PAPA-1 induced growth suppression of cells,
      and the effect was dependent on its nucleolar localization in established HeLa
      cell lines that inducibly express PAPA-1 or its deletion mutant under the control
      of a tetracycline-inducible promoter. Furthermore, when PAPA-1-inducible HeLa
      cells were synchronized by thymidine, colcemid or mimosine, and then PAPA-1 was
      expressed, the proportion of cells at the G1 phase was obviously increased. These
      results suggest that PAPA-1 induces growth and cell cycle arrests at the G1 phase
      of the cell cycle.

PMID- 15556298
TI  - Hepatic gene expression profiles in a long-term high-fat diet-induced obesity
      mouse model.
AB  - To understand the molecular mechanisms underlying alterations in the
      pathophysiologic status of dietary obesity, we examined hepatic genes
      differentially expressed in a long-term high-fat intake-induced obesity mouse
      model. C57BL/6J male mice were fed with two kinds of diets for 12 weeks; a low
      fat diet (LFD), a high-fat diet (HFD; n=8), and the expression levels of
      approximately 10,000 transcripts in liver tissues from the two groups were
      assessed using cDNA microarray analysis. Twelve-week feeding with the HFD
      resulted in significant increase in body weight, visceral fat accumulation and
      circulating cholesterol concentration, compared with the LFD group. The cDNA
      microarray analysis revealed marked differences in the expressions of 97 hepatic
      genes. These genes were categorized into seven groups:metabolism; defense,
      stress, and inflammation responses; signal transduction, apoptosis, and cell
      cycle; transcription regulation; protein synthesis and modification; transport;
      and cellular adhesion, cytoskeleton and trafficking. The expression of genes
      involved in fatty acid catabolism and ketone body synthesis, such as acyl-CoA
      oxidase1 (Acox1) and HMG-CoA lyase (Hmgcl), was significantly increased, and
      expression of genes involved in lipogenesis and cholesterol synthesis, such as
      acetyl-CoA synthetase2 (Acs2), fatty acid synthase (Fasn), and squalene epoxidase
      (Sqle), was drastically decreased in the HFD group. Interestingly, the genes
      implicated in defense and stress responses, such as glutathione S-transferases
      (GSTs) and heat shock proteins (Hsps), were also highly represented in the HFD
      group. Besides, a number of previously unappreciated regulatory molecules were
      changed by the HFD. These results revealed a transcriptional adaptation to long
      term HFD and provided interesting information about the molecules involved in the
      development and maintenance of the obesity phenotype in vivo.

PMID- 15556299
TI  - Ankyrin repeat-containing proteins in Arabidopsis: characterization of a novel
      and abundant group of genes coding ankyrin-transmembrane proteins.
AB  - Ankyrin repeats are present in a great variety of proteins of eukaryotes,
      prokaryotes and some viruses and they function as protein-protein interaction
      domains. We have search for all the ankyrin repeats present in Arabidopsis
      proteins and determined their consensus sequence. We identified a total of 509
      ankyrin repeats present in 105 proteins. Ankyrin repeat containing proteins can
      be classified in 16 groups of structurally similar proteins. The most abundant
      group contains proteins with ankyrin repeats and transmembrane domains (AtANKTM).
      Sequence similarity analysis indicates that these proteins are divided in six
      families. Some of the AtAnkTm genes are organized in tandem arrays and others are
      present in duplicated parts of the Arabidopsis genome. The expression of several
      AtAnkTm genes was analyzed resulting in a wide variety of expression patterns
      even within the same family. The likely functions of these proteins are discussed
      in comparison with the known functions of proteins with similar organization in
      other species.

PMID- 15556300
TI  - Transcriptional regulation of the murine Elf3 gene in embryonal carcinoma cells
      and their differentiated counterparts: requirement for a novel upstream
      regulatory region.
AB  - The transcription factor Elf3, which is one of over 25 Ets family members, is
      expressed in a wide variety of carcinomas and has been shown to promote the
      transcription of many genes implicated in cancer. To understand how the Elf3 gene
      is regulated at the transcriptional level, we probed its 5'-flanking region, and
      we report here the identification of both proximal and distal regions that
      regulate murine Elf3 promoter activity. In addition to mapping the transcription
      start site of the Elf3 gene, the work described in this study identifies four cis
      regulatory elements in the proximal promoter region of the gene. These include a
      cis-regulatory element previously designated ESE, a kappaB site, a POU motif, and
      a CCAAT box. In addition, we demonstrate that a novel 94 bp region 2 kb upstream
      of the transcription start site significantly elevates Elf3 promoter activity in
      F9-differentiated cells, but not in the parental F9 embryonal carcinoma (EC)
      cells. This region appears to be largely responsible for the increase in Elf3
      promoter activity that accompanies the differentiation of embryonal carcinoma
      cells.

PMID- 15556301
TI  - The complete nucleotide sequence of wild rice (Oryza nivara) chloroplast genome:
      first genome wide comparative sequence analysis of wild and cultivated rice.
AB  - We determined the complete nucleotide sequence of the chloroplast genome of wild
      rice, Oryza nivara and compared it with the corresponding published sequence of
      relative cultivated rice, Oryza sativa. The genome was 134,494 bp long with a
      large single-copy region of 80,544 bp, a small single-copy region of 12,346 bp
      and two inverted repeats of 20,802 bp each. The overall A+T content was 61.0%.
      The O. nivara chloroplast genome encoded identical functional genes to O. sativa
      in the same order along the genome. On the other hand, detailed analysis revealed
      57 insertion, 61 deletion and 159 base substitution events in the entire
      chloroplast genome of O. nivara. Among substitutions, transversions were much
      higher than transitions with the former even more frequent than the latter in the
      coding region. Most of the insertions/deletions were single-base but a few large
      length mutations were also detected. The frequency of insertion/deletion events
      was more in the coding region within inverted repeats. In contrast, a very few
      substitution events were identified in the coding region. Polymorphism was
      observed among rice cultivars at loci of large insertion/deletion events. This is
      the first report describing comparative and genome wide chloroplast analysis
      between a wild and cultivated crop.

PMID- 15556302
TI  - Gene expression profiles of early adipogenesis in human mesenchymal stem cells.
AB  - Bone marrow-derived human mesenchymal stem cells (hMSCs) give rise to adipocytes
      in response to a medium containing dexamethasone, isobutylmethylxanthine, and
      insulin. A cDNA microarray was applied to analyze the gene expression profiles
      between the cells at day 0 and at day 3 of incubation in the adipogenic medium,
      when the cells began to express PPARgamma2, a transcription factor of
      adipogenesis. Several genes that were regulated during this time period were then
      confirmed by semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR). Interestingly, several genes identified previously as markers of
      lineage-specific differentiations other than adipocyte were regulated during
      adipogenesis. We totally identified 82 genes that were differentially induced by
      fivefold or greater, and 31 genes that were differentially suppressed by twofold
      or more. Among them, 55 genes were not previously examined to associate with
      adipogenesis or have not been determined in hMSCs, therefore, these data provide
      novel information on the genes involved in adipogenesis of hMSCs.

PMID- 15556303
TI  - A large plant beta-tubulin family with minimal C-terminal variation but
      differences in expression.
AB  - Tubulins, as the major structural component of microtubules (MT), are highly
      conserved throughout the entire eukaryotic kingdom. They consist of alpha/beta
      heterodimers. Both monomers, at least in multicellular organisms, are encoded by
      gene families. In higher plants up to eight beta-tubulin isotypes, mostly
      differing in their very C-termini, have been described. These variable beta
      tubulin C-termini have been discussed in the context of functional microtubule
      diversity. However, in plants, in contrast to vertebrates, functional isotype
      specificity remains yet to be demonstrated. Unlike higher plants, unicellular
      green algae in general do not exhibit isotypic variations. The moss
      Physcomitrella patens is a phylogenetic intermediate between higher plants and
      green algae. We isolated six beta-tubulin genes from Physcomitrella, named PpTub1
      to 6. We show that the exon/intron structure, with the exception of one
      additional intron in PpTub6, is identical with that of higher plants, and that
      some members of the family are differentially expressed. Moreover, we find that
      all Physcomitrella isotypes are highly conserved and, most strikingly, are almost
      identical within their C-terminal amino acids (aa). This evolutionary ancient and
      large beta-tubulin gene family without significant isotypic sequence variation
      points to a role of differential regulation in the evolution of plant tubulin
      isotypes.

PMID- 15556304
TI  - Molecular cloning, expression and chromosomal localization of a novel human REG
      family gene, REG III.
AB  - Regenerating gene (Reg), first isolated from a regenerating islet cDNA library,
      encodes a secretory protein with a growth stimulating effect on pancreatic beta
      cells that ameliorates the diabetes of 90% depancreatized rats and non-obese
      diabetic mice. Reg and Reg-related genes have been revealed to constitute a
      multigene family, the Reg family, which consists of four subtypes (types I, II,
      III, IV) based on the primary structures of the encoded proteins of the genes
      [Diabetes 51(Suppl. 3) (2002) S462]. Plural type III Reg genes were found in
      mouse and rat. On the other hand, only one type III REG gene, HIP/PAP (gene
      expressed in hepatocellular carcinoma-intestine-pancreas/gene encoding
      pancreatitis-associated protein), was found in human. In the present study, we
      found a novel human type III REG gene, REG III. This gene is divided into six
      exons spanning about 3 kilobase pairs (kb), and encodes a 175 amino acid (aa)
      protein with 85% homology with HIP/PAP. REG III was expressed predominantly in
      pancreas and testis, but not in small intestine, whereas HIP/PAP was expressed
      strongly in pancreas and small intestine. IL-6 responsive elements existed in the
      5'-upstream region of the human REG III gene indicating that the human REG III
      gene might be induced during acute pancreatitis. All the human REG family genes
      identified so far (REG Ialpha, REG Ibeta, HIP/PAP, REG III and REG IV) have a
      common gene structure with 6 exons and 5 introns, and encode homologous 158-175
      aa secretory proteins. By database searching and PCR analysis using a yeast
      artificial chromosome clone, the human REG family genes on chromosome 2, except
      for REG IV on chromosome 1, were mapped to a contiguous 140 kb region of the
      human chromosome 2p12. The gene order from centromere to telomere was 5' HIP/PAP
      3'-5' RS 3'-3' REG Ialpha 5'-5' REG Ibeta 3'-3' REG III 5'. These results suggest
      that the human REG gene family is constituted from an ancestor gene by gene
      duplication and forms a gene cluster on the region.

PMID- 15556305
TI  - Body condition and suckling as factors influencing the duration of postpartum
      anestrus in cattle: a review.
AB  - Prolonged postpartum anestrus is a main factor limiting reproductive efficiency
      in cattle, particularly in Bos indicus and Bos taurus/Bos indicus cows from
      tropical regions, because it prevents achievement of a 12 month calving interval.
      During anestrus, ovulation does not occur despite ovarian follicular development,
      because growing follicles do not mature. Although many factors affect postpartum
      anestrus, nutrition and suckling are the major factors influencing the resumption
      of postpartum ovarian cycles, as they affect hypothalamic, pituitary and ovarian
      activity and thus inhibit follicular development. Under-nutrition contributes to
      prolonged postpartum anestrus, particularly among cows dependent upon forages to
      meet their feed requirements and it apparently interacts with genetic,
      environmental or management factors to influence the duration of anestrus. The
      nutritional status or balance of an animal is evaluated through body condition
      score (BCS), as it reflects the body energy reserves available for metabolism,
      growth, lactation and activity. There is a converse relationship between energy
      balance and time to resumption of postpartum ovarian activity; inadequate
      nutrient intake results in loss of weight and BCS and finally cessation of
      estrous cycles. Suckling interferes with hypothalamic release of GnRH, provoking
      a marked suppression in pulsatile LH release, resulting in extended postpartum
      anestrus. The effects of suckling on regulation of tonic LH release are
      determined by the ability of the cow to identify a calf as her own or as
      unrelated. Vision and olfaction play critical roles in the development of the
      maternal-offspring bond, allowing the cow to identify her own calf, and abolition
      of both senses attenuates the negative effects of suckling on LH secretion. Thus,
      the maternal-offspring bond is essential for prolonged postpartum suckling
      induced anovulation, and the suppressive influence of suckling is independent of
      neurosensory pathways within the teat or udder.

PMID- 15556306
TI  - Oestradiol-17beta responsiveness, plasma LH profiles, pituitary LH and FSH
      concentrations in long-term ovariectomised Holstein cows at 24 h, 48 h and 21
      days following treatment with an absorbable GnRH agonist implant.
AB  - Non-lactating OVX Holstein cows (N = 34) were used to investigate the effect of
      s.c. placement of an absorbable GnRH agonist implant (Ovuplant; deslorelin 2.1mg,
      Peptech Animal Health, Australia) on the relationship of plasma LH, oestradiol
      responsiveness and pituitary LH content. On the day of implant insertion (Day 0),
      one group (OVU-48h; N = 5) received Ovuplant and had blood samples collected at
      hourly intervals to characterize the LH response, while a second group (CON-48 h;
      N = 5) remained untreated and acted as controls. Blood samples were collected
      every 10 min over 6 h from CON-48 h and OVU-48 h, at 24 h post-implant insertion.
      These cows were then slaughtered at 48 h post-implant insertion and their
      pituitaries recovered. Another group received Ovuplant (OVU-21d+E2; N = 10) or
      were left untreated (CON-21d+E2) and 21 days later were injected i.m. with 0.5 mg
      17beta-E2. Blood samples were collected every 10 min for 4 h on the day before E2
      injection to characterize LH pulse frequency and amplitude. Beginning 14 h later,
      blood samples were collected hourly for 12 h to characterize the expected LH
      surge. These cows were slaughtered and their pituitary glands recovered and
      assayed for LH and FSH content. Peak plasma LH concentrations (59 +/- 19 ng/ml)
      were measured after 30 min of Ovuplant insertion. They had returned to pre
      treatment levels by 7 h. By 24 h post-implant insertion, OVU-48 h plasma LH
      profiles were characterized by reduced LH pulse frequency (0.23 +/- 0.09 pulses/h
      versus 0.75 +/- 0.26 pulses/h; OVU-48 h versus CON-48 h; P < 0.05). The cows that
      received Ovuplant had lower LH pulse amplitude, LH pulse frequency and mean LH
      concentrations after 20 days. Injection of 0.5 mg 17beta-E2 induced an LH surge
      in every one of the control cows with their peak concentrations measured 18 h
      post injection. No increase in LH was detected in any Ovuplant treated cows.
      Pituitary FSH content was reduced in Ovuplant treated cows after 48 h, but not
      that of LH. In conclusion, absorbable deslorelin implants induced a substantial
      but temporary release of LH, but even 21 days later their LH profiles were
      characterized by marked suppression of pulsatile LH and an absence of response to
      E2. These results suggest the implant has prolonged biological activity.

PMID- 15556307
TI  - Effects of leptin on gonadotropin-releasing hormone release from hypothalamic
      infundibular explants and gonadotropin release from adenohypophyseal primary cell
      cultures: further evidence that fully nourished cattle are resistant to leptin.
AB  - In rodents and pigs, leptin stimulates the release of gonadotropin-releasing
      hormone (GnRH) from hypothalamus, gonadotropins from adenohypophyseal (AP)
      explants and cells, and luteinizing hormone (LH) from full-fed animals. In the
      current studies, we investigated whether leptin could stimulate the release of
      GnRH from bovine hypothalamic-infundibular (HYP) explants and gonadotropins from
      bovine adenohypophyseal cells. In Experiment 1A, HYP explants collected from 17
      bulls and seven steers were incubated with Krebs-Ringer bicarbonate buffer (KRB)
      containing 0, 10, 100, or 1000 ng/ml recombinant ovine leptin (oleptin) for 30
      min after a 3-h period of equilibration. None of the doses of leptin affected (P
      > 0.05) GnRH release into the media. In Experiment 1B, HYP explants collected
      from six steers were incubated with KRB containing 0 or 1000 ng/ml oleptin for
      two consecutive 30-min periods and challenged with 60 mM K(+) afterwards. Leptin
      did not affect (P > 0.05) basal or K(+)-stimulated release of GnRH. In Experiment
      2, adenohypophyses from steers were collected at slaughter and cells dispersed
      and cultured for 4 days. On day 5, cells were treated with media alone (control)
      or media containing 10(-11), 10(-10), 10(-9), and 10(-8)M oleptin. Three
      independent replications were performed. None of the doses of leptin stimulated
      (P > 0.05) the release of LH. Although leptin at 10(-11), 10(-10), and 10(-9)M
      increased (P < 0.03) slightly the release of FSH compared to control-treated
      cells in one replicate, this effect was not confirmed in the other two
      replicates. Results support the hypothesis that leptin has limited effects on the
      release of GnRH and gonadotropins in full-fed cattle and reiterate important
      species differences in responsiveness to leptin.

PMID- 15556308
TI  - Developmental competence of oocytes from prepubertal Bos indicus crossbred
      cattle.
AB  - The aim of the present study was to evaluate the effect of age on embryogenic
      competence of oocytes recovered from Bos indicus crossbred calves and heifers.
      Cumulus-oocyte complexes (COCs) were collected from 4- to 7-month-old calves
      (experiment 1) and from 9- to 14-month-old heifers (experiment 2) during
      processing at an abattoir. In both experiments cow COCs were used as control.
      COCs were in vitro matured and fertilized, and the presumptive zygotes co
      cultured with cumulus cells until 224 h post insemination (hpi). In experiment 1,
      the development rate during the first 68-72 hpi was similar (P > 0.05) between
      embryos derived from calves and cows. Fewer embryos from calves developed to the
      blastocyst stage, resulting in a lesser blastocyst production as well as lesser
      hatching rate (P < 0.05). The embryo development after blastocyst stage was,
      nevertheless, similar (P > 0.05) between blastocysts derived from calves and
      cows, suggesting that the development after blastocoele formation is not
      compromised in embryos derived from calves. In experiment 2, there were no
      differences (P > 0.05) on cleavage, blastocyst and hatching rates between embryos
      derived from prepubertal heifers and cows. The rate of blastocyst development
      until hatching was also similar (P > 0.05). These results indicate that oocytes
      from 9- to 14-month-old B. indicus crossbred heifers have the same developmental
      competence as oocytes derived from cows, while ocytes derived from 4- to 7-month
      old B. indicus crossbred calves are less competent in developing to the
      blastocyst stage in vitro. It suggests that oocyte competence in B. indicus
      crossbred cattle is achieved around 9-14 months of age.

PMID- 15556309
TI  - Effects of prepartum lipid supplementation on FSH superstimulation and
      transferable embryo recovery in multiparous beef cows.
AB  - The objective of this experiment was to determine the effect of prepartum lipid
      supplementation on the number and quality of embryos recovered following ovarian
      super-ovulation in postpartum suckled beef cows. Mature cows (n = 40) were
      assigned to one of two treatments (lipid versus. no lipid) and supplemented for
      approximately 40 days prior to calving. Supplements provided to cows were
      isocaloric and isonitrogenous. The treatment group was fed 1.6 kg hd(-1) per day
      of whole soybeans (WSB; 19.8% ether extract, and 41.8% crude protein) and the
      control group received a supplement consisting of 1.8 kg hd(-1) day of a soybean
      meal and soy-hull combination (SBS; 2.15% EE and 36.81% CP). Cows were
      synchronized using a GnRH [Cystorelin((R)) 100 microg im]-GnRH-PGF(2alpha)
      [Lutalyse 25 mg im] protocol. Cows were administered two injections of GnRH seven
      days apart and PG seven days after the second GnRH injection. Twenty-eight cows
      (WSB, n = 15; SBS, n = 13) responded to estrus synchronization and were
      superstimulated. Super-ovulation was initiated on day 8-10 of the synchronized
      cycle by twice-daily injections of pFSH (Pluset) over four days in decreasing
      doses using a total of 608.4 IU per cow. Prostaglandin F(2alpha) was administered
      96 and 108 h after super-stimulation was initiated with FSH. Days postpartum (WSB
      = 59 days; SBS = 57 days) at initiation of FSH treatments were similar (P > 0.10)
      for both treatments. Cows were monitored for estrus activity by the HeatWatch
      Estrus Detection System. Twenty-seven cows (WSB, n = 15; SBS, n = 12) exhibited
      estrus after FSH and inseminated at 0, 12, and 24 h after the onset of estrus
      with 1, 2, and 1 units of semen, respectively. Embryos were recovered and
      evaluated 7-8 days later. Only cows that responded to FSH and that were
      inseminated were used for statistical analysis. Data were analyzed using the
      General Linear Models Procedure of SAS. Body condition scores did not differ (P >
      0.10) between treatments when cows were evaluated at the initiation of the
      experiment, two weeks prior to calving, and at initiation of superovulation with
      FSH. Estrous cyclicity prior to the initiation of estrus synchronization did not
      differ (P > 0.10) between treatments. There was no difference (P > 0.10) between
      treatments in recovery of total embryos (WSB, 14.7 +/- 3.5; SBS, 17.5 +/- 3.0),
      transferable embryos (WSB, 10.3 +/- 2.5; SBS, 13.6 +/- 2.6), degenerate embryos
      (WSB, 3.3 +/- 1.1; SBS, 1.6 +/- 1.7) or unfertilized ova (WSB, 1.1 +/- 0.5; SBS,
      2.3 +/- 1.2). Cows that were supplemented with whole soybeans prior to
      parturition failed to produce an increased total number of ova or transferable
      embryos following super-ovulation.

PMID- 15556310
TI  - Superovulation and embryo recovery from peripubertal Holstein heifers.
AB  - The use of peripubertal donors in embryo transfer (ET) programs presents
      significant opportunity to accelerate genetic gain in domestic livestock by
      reducing the generation interval. These studies were designed to evaluate
      feasibility of superovulation and embryo recovery in peripubertal heifers
      (starting at 7.8 months of age), and to determine whether subsequent reproductive
      and lactational performance of donor heifers were impaired. Study 1 utilized 10
      pairs of contemporary full-sibling heifers in which one heifer in each pair was
      assigned to receive a superovulation regimen and her full-sibling contemporary
      received placebo. Treated heifers were artificially inseminated at estrus and
      embryos were flushed transcervically 4-6 days later. Based on recovery of oocytes
      and/or embryos, 9 of 10 heifers responded to the hormonal regimen and 12 total
      embryos were recovered. Seven embryos (58%) were transferred into recipients
      resulting in five pregnancies. Control and treated heifers remained in the herd
      and were bred at a natural estrus by AI at 15 months of age. Lactation records,
      i.e., 305 days mature equivalent (305 d ME) were obtained, and all animals were
      evaluated for udder conformation traits between 32 and 38 months of age.
      Reproductive traits (age at first calving and days to conception) and lactational
      traits of heifers subjected to embryo transfer and their non-treated full
      siblings did not differ (P > 0.05). Study 2 was conducted to establish the
      commercial feasibility of hormonally programming peripubertal heifers ranging in
      age from 7.8 to 9.9; 10 to 11.9; 12 to 13.9 and >/= 14 months. In total, 3982
      embryos were recovered from 520 heifers, with 2419 (60.7%) of those categorized
      as viable (transferable). The number of ova/embryos obtained per flush (5.6 +/-
      1.0) and the number of transferable embryos (2.8 +/- 0.5) was reduced (P < 0.05)
      in heifers of age 7.8-9.9 months compared to all other age groups. There was no
      difference (P > 0.05) in the number of ova/embryos recovered (7.8 +/- 0.3), or
      the number of transferable embryos (4.8 +/- 0.2), among heifers that were >/=10
      months of age. The number of unfertilized ova did not differ by age, however,
      more degenerate embryos tended to be recovered from heifers <10 months of age
      compared to heifers >/=14 months of age. These data indicate that transferable
      embryos can be safely recovered from heifers beginning at 10 months of age
      without compromising subsequent reproductive or lactational performance of the
      donor.

PMID- 15556311
TI  - The effect of Mycoplasma mycoides ssp. mycoides LC of bovine origin on in vitro
      fertilizing ability of bull spermatozoa and embryo development.
AB  - Several Mycoplasma species may adversely affect bovine spermatozoa viability and
      embryo development. Mycoplasma mycoides ssp. mycoides large-colony (LC) has been
      isolated from naturally aborted bovine fetuses and from bull semen. The objective
      of this study was to evaluate whether M. mycoides ssp. mycoides LC contaminated
      bovine ejaculates could (i) impair in vitro fertilizing ability of bull
      spermatozoa, (ii) impair embryo development, and (iii) evaluate potential spread
      by reproductive technologies. In the present study, spermatozoa of 10 fertile
      bulls were contaminated with M. mycoides ssp. mycoides LC, at a final
      concentration of 1.5 million CFU/ml and incubated for 60 min before evaluating
      spermatozoa motility and acrosome reaction inducibility with calcium ionophore.
      In addition, in vitro contaminated semen of a bull previously shown to have a
      good in vitro fertilizing ability, was used in an IVF procedure. Embryo
      development stage on Day-7 of culture was evaluated. Spermatozoa and embryos at
      morula and blastocyst stages were routinely processed for transmission electron
      microscopy observation. Both mean total and progressive motility decreased (P <
      0.01 ) upon spermatozoa incubation with Mycoplasma. One-hour incubation with
      calcium ionophore increased the percentage of acrosome-reacted spermatozoa,
      although Mycoplasma contamination reduced calcium ionophore treatment efficacy (P
      < 0.05). Ultrastructurally, Mycoplasma microorganisms appeared as moderately
      electron-dense sphere-shaped particles, adhering to cell membranes. Sperm mid
      piece sections showed numeric aberrations of the central singlets such as nine +
      zero or nine + one of the axonemal complex. Further morphological abnormalities
      included partial or total absence of dinein arms and radial fibers, with lack of
      the bridge and the central ring in 35.00 +/- 4.20% of contaminated cells, whereas
      these abnormalities were not observed in uninfected ones. The IVF trials showed
      that two-four cell blocks were higher (P < 0.05) in the infected group.
      Ultrastructure of Day-7 contaminated embryos showed Mycoplasma particles adhering
      and infiltrating the outer layer of the zona pellucida. Our investigations
      suggest that M. mycoides ssp. mycoides LC contaminating the bovine ejaculate
      induced adverse effects on in vitro spermatozoa-fertilizing ability and embryonic
      development. Some satisfactory quality transferable embryos could be produced in
      contaminated IVF systems. This could imply a potential transmission of this
      microorganism through reproductive technologies.

PMID- 15556312
TI  - Phenotypic relationships between hair whorl characteristics and spermatozoal
      attributes in Holstein bulls.
AB  - The objective of this study was to characterize facial whorl characteristics in
      Holstein stud bulls (n = 485) and to investigate their association with measures
      of semen quantity and quality. Bulls had 1 (n = 454), 2 (n = 21) or no facial
      hair whorls (n = 5). Some 39% of bulls had whorls in the middle of their
      forehead, whereas 43% had whorls very low down on their forehead. Spiral whorls
      were present on 77% of bulls while 22% had elongated whorls. Abnormally shaped
      whorls were found more often on bulls with low whorls (27% versus 17%, P = 0.01)
      than on bulls with high or middle whorls. Semen production data were obtained
      from the AI center database to provide a representative sample of each sires most
      recent semen production characteristics. The number of semen collections per bull
      averaged 38 with a range of 1 (n = 9) to 272 (n = 1). The average number of days
      between collections was 5 but varied from 1 to 425 days. Average age of bulls at
      first recorded collection was 679 days and ranged from 307 to 4555 days. There
      were no significant differences between black and white bulls in semen quality or
      quantity. Semen quality over the summer months was reduced in comparison to the
      winter months. Age of the bull at time of collection had no effect on any of the
      semen quality traits. Older bulls had larger scrotal circumference and produced
      more semen (P > 0.01). Bulls with whorls located in the center of the forehead
      were not significantly different in semen quality or quantity for the 10 traits
      considered when compared to bulls with whorls located outside the center. In
      contrast to previous research findings with Angus cattle, semen attributes were
      not significantly different between bulls characterized with round (or spiral)
      epicenters and those with abnormally shaped whorls. The difference between the
      two studies may be due to the fact that Angus bulls have a higher percentage of
      abnormal elongated whorls compared to Holsteins.

PMID- 15556313
TI  - A comparison of morphometric characteristics of sperm from fertile Bos taurus and
      Bos indicus bulls in Brazil.
AB  - The current work has as main objective the systematic investigation of sperm
      morphometric characteristics of fertile Bos taurus and Bos indicus bulls living
      in Brazil by using several traditional as well as more modern and advanced
      computer vision concepts and methodologies. Ten smears of B. taurus semen and ten
      smears of B. indicus semen have been evaluated. Sperm morphology was quantified
      in terms of the following morphological features: head area, perimeter, width,
      length, width:length ratio, ellipticity, shape factor, width of sperm basis, the
      three first Fourier values, symmetry and hydrodynamics. Morphometric differences
      have been observed between the sperm cell of B. taurus and B. indicus bulls. The
      sperm cells of Zebu bulls tend to be smaller and less elliptic, however without
      modifying hydrodynamic, side symmetry and width of sperm head base. These
      differences clearly indicate that the geometrical characterization of bull sperm
      cells should take into account morphological peculiarities that are specific to
      each subspecies. Another important contribution is the identification that
      morphological differences implied by bulls of different fertility, as
      characterized by other authors, were found to be less as compared with those
      obtained in the current study where highly fertile animals from the two
      subspecies were studied.

PMID- 15556314
TI  - Induction of estrus in non-lactating dairy goats with different estrous synchrony
      protocols.
AB  - The objective of this study was to evaluate two protocols of estrous
      synchronization in non-lactating Toggenburg goats. Nineteen goats were allocated,
      according to body condition score and weight, into two groups (A and B) and
      evaluated utilizing two treatments (T1 and T2). Animals in the T1 and T2 groups
      received an intravaginal sponge (day 0) containing 60 mg medroxyprogesterone
      acetate for 6 and 9 days, respectively, plus 200 IU equine chorionic
      gonadotrophin (eCG) and 22.5 microg cloprostenol 24 h before sponge removal.
      Females were bred only at the second estrus and received 22.5 microg cloprostenol
      7 days later to prevent pregnancy. Percentages of animals in estrus did not
      differ (P > 0.05) between T1 (89.5%) and T2 (84.2%). From 33 females in estrus
      (T1 + T2), 28 (84.8%), 2 (6.1%), and 3 (9.1%) were identified in estrus at 06:00,
      12:00 and 18:00 h, respectively. Additionally, 6 (18.2%), 0 (0.0%) and 27 (81.8%)
      were no longer detected to be on estrus at 06:00, 12:00 and 18:00 h,
      respectively. Interval from sponge removal and the onset of estrus (IE) did not
      differ (P > 0.05) between T1 (46.1 +/- 15.0 h) and T2 (53.6 +/- 16.1 h). Duration
      of estrus did not differ (P > 0.05) between T1 (30.0 +/- 12.0 h) and T2 (27.2 +/-
      11.2 h). Both protocols were effective in inducing estrus in non-lactating goats.
      The onset and end of the estrus relative to hour of the day should be considered
      in estrous detection, natural breeding, and artificial insemination in goats.

PMID- 15556315
TI  - Hysteroscopic or rectally guided, deep-uterine insemination of mares with
      spermatozoa stored 18 h at either 5 degrees C or 15 degrees C prior to flow
      cytometric sorting.
AB  - Practical application of sex-selected spermatozoa in the horse industry would be
      greatly improved by the ability to develop simplified methods for shipping,
      storing, and inseminating sex-selected spermatozoa. Acceptable pregnancy rates
      have been achieved using fresh sex-sorted stallion sperm, however many stallion
      owners are reluctant to send their stallions to the sorter location for
      collection during the breeding season. Furthermore, the technology would be more
      applicable if the hysteroscopic insemination technique was not necessary for
      adequate pregnancy rates. Hysteroscopic insemination requires expensive equipment
      and specially trained personnel. In the present study, stallion sperm were sex
      sorted after being stored at either 5 degrees C or 15 degrees C for 18 h. Twenty
      million sex-sorted sperm were then inseminated using one of two insemination
      techniques: the hysteroscopic method or the rectally guided, deep-uterine
      technique. Results were determined based on 16-day pregnancy status. A first
      cycle pregnancy rate of 72% (18/25) was achieved when sperm were shipped at 15
      degrees C, sex-sorted, and then inseminated using the hysteroscopic method. With
      these results, it can be concluded that stallions are not necessary at the sorter
      location to achieve acceptable fertility with sex-sorted sperm. There was a
      tendency for more mares to become pregnant when sperm were shipped at 15 degrees
      C prior to sorting, when compared to shipment at 5 degrees C. Similarly, there
      was a tendency for more mares to become pregnant when hysteroscopic insemination
      was utilized, when compared to the rectally guided, deep-uterine technique. These
      trends suggest that if larger group numbers were available, significant
      differences between the treatments may be revealed.

PMID- 15556316
TI  - Urinary excretion of collagen degradation markers by sows during postpartum
      uterine involution.
AB  - Incomplete uterine involution is the putative cause of the increased embryo
      mortality and reproductive failure often exhibited by sows that lactate for less
      than 21 days. Since such short lactation lengths are common in American swine
      production, an effective technique to monitor the postpartum involution process
      and test this hypothesis might be valuable. Rapid and extensive catabolism of
      uterine collagen is essential for normal postpartum involution. The objective of
      this study was to characterize postpartum excretion of two biochemical markers of
      collagen degradation. In experiment I, urine samples were collected from five
      sows every other day from the day before parturition (day -1), through a 21-day
      lactation, to day 8 postweaning. The collagen crosslinks hydroxylysyl
      pyridinoline (HP), which is present in many tissues, and lysyl pyridinoline (LP),
      which is primarily concentrated in bone, were assayed by both ELISA and HPLC.
      Urinary levels of both free (ELISA) and total (HPLC) HP and LP increased (P <
      0.001) approximately two-fold during lactation. The mean molar ratio of total
      HP:LP increased (P < 0.001) from 6.6 +/- 1.6 at day 1 to a maximum of 10.2 +/-
      1.5 at day 7 postpartum and averaged 9.1 +/- 0.3 for the entire sampling period.
      These data are consistent with a postpartum increase of soft tissue collagen
      catabolism since bone has a low HP:LP ratio of 4 and soft tissues like the uterus
      have a high HP:LP ratio of >/=20 because they contain only trace amounts of LP.
      Since HPLC (total) and ELISA (free) crosslinks estimates were highly correlated
      (r = 0.85-0.91, P < 0.001) in experiment I, only the less technical ELISA
      technique was used in experiment II. Urine samples were collected from 21 sows
      every third day from day 1 to 19 of lactation. Sows from this second group
      exhibited one of four distinct crosslinks excretion patterns: peak on day 1 (n =
      3), peak on day 7 (n = 4), peak on day 10, 13 or 16 (n = 7), or no peak (n = 7).
      This variation of postpartum crosslinks excretion among sows was not related to
      parity, body weight, lactation body weight change, litter size, or litter birth
      weight. Overall, data from experiments I and II indicate that urinary HP does
      increase postpartum in a pattern temporally consistent with uterine involution.
      However, significant variation among sows in the magnitude and timing of peak HP
      excretion was evident.

PMID- 15556317
TI  - Ovarian and placental production of progesterone and oestradiol during pregnancy
      in reindeer.
AB  - We obtained uterine and peripheral venous plasma, and samples of luteal and
      placental tissues from 2- to 7-year-old, Eurasian mountain reindeer (Rangifer
      tarandus tarandus) from a free-living, semi-domesticated herd in northern Norway
      in November 1995, and February and March 1996. In November, ovarian venous blood
      was also collected from four animals. Plasma samples were assayed for
      progesterone and oestradiol. The tissue samples were examined by light and
      electron microscopy, steroid dehydrogenase histochemistry, and northern blot
      analysis for RNAs for 3beta-hydroxy-steroid dehydrogenase (3beta-HSD) and P450
      (side chain cleavage (scc)). Peripheral blood was taken from non-pregnant females
      in the same herd on the same dates. Peripheral progesterone concentrations in
      pregnant reindeer (3.4 +/- 0.5 ng/ml, n = 8) clearly exceeded those in non
      pregnant animals (0.40 +/- 0.14 ng/ml; P < 0.0004 , n = 10) but oestradiol levels
      were only marginally higher in pregnant (6.0 +/- 0.7 pg/ml) than in non-pregnant
      (4.8 +/- 0.5 pg/ml; P = 0.35) reindeer at the stages examined. In pregnant
      animals, peripheral progesterone and oestradiol concentrations rose slightly
      between November and March but the differences did not reach significance
      (progesterone, P = 0.083; oestradiol, P = 0.061). In November, progesterone
      concentrations in the ovarian vein (79 +/- 15 ng/ml) greatly exceeded (P < 0.03)
      those in the uterine vein ( 10 +/- 4 ng/ml) which in turn exceeded the levels in
      the peripheral blood (2.8 +/- 0.4 ng/ml; P < 0.29). Oestradiol concentrations
      were slightly but significantly (P < 0.05) higher in the ovarian (20 +/- 3 pg/ml)
      than the uterine vein (13 +/- 1 pg/ml) and, in turn, greater (P < 0.03) than in
      peripheral blood (4.6 +/- 0.4 pg/ml). All samples of luteal tissue consisted
      exclusively of normal fully-differentiated cells and stained intensely for 3beta
      HSD. Isolated groups of placental cells also stained strongly for 3beta-HSD. RNA
      for P450 (scc) and 3beta-HSD was abundant in all corpora lutea and lower
      concentrations of P450 (scc) were present in the placenta. 3beta-HSD RNA in the
      placenta was below the limit of detection. We conclude that the corpus luteum
      remains an important source of progesterone throughout pregnancy in reindeer but
      that the placenta is also steroidogenic.

PMID- 15556318
TI  - Robots in the operating theatre--chances and challenges.
AB  - The use of surgical robots and manipulators is still being frequently discussed
      in the mass media as well as in the scientific community. Although it was already
      noted in 1985 that the first patient was treated by a joint team of robot and
      surgeon, today such systems are not routinely used. This can be explained by the
      high complexity of such systems and the often limited usability, but also, that
      it is difficult for surgeons to accept "automatic" machines. In this paper the
      possibilities and chances of robots and manipulators will be explained and it
      will be shown that robots will never work alone in the operating theatre as it is
      common in industry today. On the other hand, also limitations and challenges will
      be outlined. Therefore first a review on today's systems is given in different
      disciplines including oral- and cranio-maxillofacial surgery, then advantages and
      disadvantages are shown.

PMID- 15556319
TI  - Reconstruction of the mandible using preshaped 2.3 mm titanium plates, autogenous
      particulate cortico-cancellous bone grafts and platelet rich plasma: a report on
      eight patients.
AB  - The results are presented of eight patients who had partial mandibulectomies for
      malignant tumours and were secondarily reconstructed with pre-shaped 2.3 mm
      titanium plates, autogenous particulate cortico-cancellous bone grafts and
      platelet rich plasma. Healing was uneventful in all cases and when
      prosthodontically needed, implants were inserted after approximately 6 months,
      whilst biopsies were taken. The histology showed bone remodelling in six cases,
      whilst in one case after 6 months the bone was largely replaced by abundant
      fibrous tissue. In this case the implants were lost after 9 months. In one case a
      new carcinoma developed after 6 months with subsequent death of the patient.
      Thus, in six patients adequate results were achieved with adequate functional and
      aesthetic outcome, given the poor conditions of the surrounding tissues. This
      method provides three-dimensional reconstruction with sufficient bone height and
      volume to facilitate prosthodontic treatment.

PMID- 15556320
TI  - Prototype of simulation of orthognathic surgery using a virtual reality haptic
      device.
AB  - A maxillofacial simulator can support education and training. In the present
      study, cutting, separation, and quantitative rearrangement of bone during
      orthognathic surgery were simulated by means of a haptic device with virtual
      tactile perception. Computed tomographic (CT) images of two patients with severe
      jaw deformity, one women and one man, were input into the device. In the woman,
      Le Fort I osteotomy of the maxilla and sagittal splitting ramus osteotomy of the
      mandible were initially simulated. During surgery with the haptic device,
      separation and rearrangement of the maxilla and the ramus of the mandible were
      initially processed. However, there was discrepancy and overlapping of the ramus
      with the mandible. Intraoral vertical osteotomy of the right ramus was then
      performed, with satisfactory results and less discrepancy and interference. The
      simulation was referred to at surgery, and satisfactory surgical assistance was
      postoperatively confirmed on CT images. The male patient had severe jaw deformity
      due to unequal growth between the ramuses, resulting in anterior crossbite.
      Sagittal splitting ramus osteotomy with rotation of the mandible was successfully
      simulated. Because of its versatility and functions, the present device was found
      to be useful for simulating various procedures for orthognathic surgery and
      thereby three-dimensionally determine surgical movements.

PMID- 15556321
TI  - Post-trauma mucocele formation in the frontal sinus; a rationale of follow-up.
AB  - The aim of the investigation was the evaluation of the follow-up for mucocele
      formation as a complication of frontal sinus fractures. A review of the
      literature was performed which showed only 10 adequately documented cases of
      mucocele formation after trauma. In our hospital between June 2001 and July 2002
      three patients were treated for mucocele as a late complication following trauma
      to the frontal sinus. Our patients presented themselves with a mucocele,
      respectively 13, 22 and 35 years after the initial trauma. From this a suggestion
      is done for the follow-up of post-trauma patients. Mucocele formation is a
      complication, which can develop years after trauma to the frontal sinus.
      Treatment of these forms of mucocele is multidisciplinary. The review of the
      literature in combination with our own data showed no peak incidence of mucocele
      formation after trauma. We therefore advocate following the at-risk-patients for
      life, and to properly inform them about the possible development and symptoms,
      like swelling, diplopia, etc., of a mucocele.

PMID- 15556322
TI  - The interpositional dermis-fat graft in the management of temporomandibular joint
      ankylosis.
AB  - The aim of this retrospective clinical study is to present the clinical
      experience of using dermis-fat interpositional grafts in the surgical management
      of temporomandibular joint (TMJ) ankylosis in adult patients. Eleven adult
      patients who presented with ankylosis of the TMJ were identified and included in
      the study. All patients underwent a TMJ gap arthroplasty which involved the
      removal of a segment of bone and fibrous tissue between the glenoid fossa and
      neck of the mandibular condyle. The resultant gap was filled with an autogenous
      dermis-fat graft procured from the patient's groin. All patients were followed up
      for a minimum of 2 years. Five of the 11 patients were found to have osseous
      ankylosis while 6 patients had fibro-osseous ankylosis. Two patients had
      bilateral TMJ ankylosis that were also treated with costochondral grafts which
      were overlaid with dermis-fat graft. The average interincisal opening was 15.6 mm
      on presentation which improved to an average of 35.7 mm following surgery.
      Patients were followed up from 2 to 6 years post-operatively (mean 41.5 months)
      with only 1 re-ankylosis identified out of the 13 joints treated. This study
      found that the use of the autogenous dermis-fat interpositional graft is an
      effective procedure for the prevention of re-ankylosis up to 6 years following
      the surgical release of TMJ ankylosis.

PMID- 15556323
TI  - Primary malignant melanoma of the oral cavity: assessment of outcome from the
      clinical records of 35 patients.
AB  - Oral malignant melanoma is extremely rare and carries a poor prognosis. The
      treatment of choice remains controversial. We retrospectively studied 35 patients
      with primary malignant melanoma of the oral cavity between 1970 and 2001 to
      define the clinical features of this disease and evaluate treatment methods. The
      main variables studied were clinical findings, response to therapy, and outcome.
      Surgery with complete macroscopic resection was performed at the primary site in
      13 patients (surgery group) and radiotherapy was done without surgery in 17 (non
      surgery group). The 5-year cumulative survival rate was 15.4% in the surgery
      group, 35.3% in the non-surgery group, and 21.8% overall. Distant metastasis was
      present in 64.7% (11/17) of the non-surgery group and 76.9% (10/13) of the
      surgery group. Improved outcome in oral malignant melanoma requires the
      development of new therapies and the prevention of distant metastasis.

PMID- 15556324
TI  - Ectodermal odontogenic tumours: analysis of 197 Nigerian cases.
AB  - This article presents a clinico-pathologic analysis of 197 cases of ectodermal
      odontogenic tumours archived in the Lagos University Teaching Hospital, Lagos
      Nigeria over a 21-year period. They were categorized according to the WHO
      classification of odontogenic tumours. Of the 197 cases, 182 (92.3%) were benign
      while 15 (7.6%) were malignant. Central ameloblastoma, which accounted for 88.3%
      in this series, was the most common benign neoplasm demonstrating predilection
      for males (58.6%) and the mandible (83.3%). The mean age of occurrence (+/-SD)
      was 31.00 +/- 13.9 (range 9-82 years). Similarly ameloblastic carcinoma was the
      most prevalent malignant tumour (5.6%) with a predilection for females (63.6%)
      and the mandible (81.8%). The mean age of occurrence (+/-SD) was 30.1+/- 20.7
      (range 16-85) years. Follicular ameloblastoma was found to be the commonest
      histologic subtype seen in Nigeria.

PMID- 15556325
TI  - Preoperative ketorolac has a preemptive effect for postoperative third molar
      surgical pain.
AB  - There is uncertainty regarding the role of preemptive analgesia in preventing
      postoperative pain. Most previous studies were of parallel design completed under
      general anesthesia with many confounding inter-patient's variables. The present
      study evaluated the efficacy of preemptive ketorolac in a crossover design in
      patients undergoing bilateral mandibular third molar surgery. This was a double
      blind, randomized, placebo-controlled study where 34 patients had each of their
      identical impacted mandibular third molars removed under local anesthesia on two
      occasions. Each patients acted as their own control; one side was pretreated with
      intravenous ketorolac 30 mg before surgery followed by placebo injection after
      surgery, and for the other side, the patient was given placebo injection before
      surgery and post-treated with intravenous ketorolac 30 mg after surgery. The
      difference in postoperative pain between pretreated and post-treated side in each
      patient was assessed by four primary end-points: pain intensity as measured by a
      100-mm visual analogue scale hourly for 12 h, time to rescue analgesic,
      postoperative analgesic consumption, and patient's global assessment. Throughout
      the 12-h investigation period, patients reported significantly lower pain
      intensity scores in the ketorolac pretreated sides when compared with the post
      treated sides (P = 0.003). Patients also reported a significantly longer time to
      rescue analgesic (8.9 h versus 6.9 h, P = 0.005), lesser postoperative analgesic
      consumption (P = 0.007) and better global assessment for the ketorolac pretreated
      sides (P = 0.01). Pretreatment with intravenous ketorolac has a preemptive effect
      for postoperative third molar surgery and extended the analgesia by approximately
      2 h.

PMID- 15556326
TI  - Microneural anastomosis using cyanoacrylate adhesives.
AB  - We have developed a reliable method of microneural anastomosis using
      cyanoacrylate adhesives. This method involves overlapping the epineuriums of the
      two nerve ends and then applying two or three microdrops of cyanoacrylate
      adhesive on the surface of the epineurium just where the epineuriums overlap. The
      sciatic nerves of Sprague-Dawley rats were transected and repaired either with 10
      0 nylon sutures or by using the described method. Histological evaluation showed
      no significant difference in the outcome of nerve regeneration between the two
      groups. It was concluded that the cyanoacrylate repair deserves to be considered
      as an alternative to the conventional suture technique in microneural
      anastomosis.

PMID- 15556327
TI  - Topography of the outer mandibular symphyseal region with reference to the
      autogenous bone graft.
AB  - The mandibular symphysis is preferred as a donor site for the relatively small
      grafts needed for the autogeneous bone graft procedure. This study was undertaken
      to determine the morphology and composition of the cortical and trabecular bone
      in the mandibular symphyseal region using 35 mandible specimens from Koreans. The
      topographical patterns through the thickness of the cortical plate and the width
      of the trabecular bone were observed. In this study, the labial cortical plate of
      the mandible became thicker from the superior to the inferior aspects (P < 0.05).
      However, the trabecular bone width exhibited a different distribution pattern
      compared to the thickness of the labial cortical plate. This observation
      concerning the cortical and trabecular bones assists in determination of the
      depth of osteotomy. The results provide useful information on the mandibular
      symphysis graft prior to dental implant placement. These results will enable the
      volume of the cortical plate in the mandibular symphyseal region and its proper
      size, depth, and location to be predicted when removing a graft block.

PMID- 15556328
TI  - The zygomatic bone as a potential donor site for alveolar reconstruction--a
      quantitative anatomic cadaver study.
AB  - The aim of this cadaver study was to evaluate the possibility of using the
      zygomatic bone as an intraoral bone harvesting donor site and to determine the
      safety of this harvesting procedure. In addition, the volume of bone material
      harvested from the zygomatic bone was measured. Twenty fixed adult cadavers were
      used to yield a total of 40 zygomatic bone harvest sites, from which bone was
      collected. The volume of bone obtained from the zygomatic harvests was measured
      with a water displacement method and by compressing the graft into a syringe. The
      safety of the technique was evaluated by assessing possible encroachment upon the
      neighbouring structures. After bone harvesting, the zygomatic sites were exposed
      and evaluated for visible perforations or fractures. Possible damage to the
      neighbouring tissues was also examined with computed tomography scans at 18 sites
      in nine cadavers. The average bone graft volume obtained from the zygomatic bone
      was measured to be 0.53 ml (SD 0.25) with water displacement and 0.59 ml (SD
      0.26) with the syringe. The complications in the zygoma included 15 small
      perforations into the maxillary sinus and 7 perforations into the infratemporal
      fossa. CT scans showed that bone could be harvested safely without encroaching
      upon the orbital floor or the surrounding nerves and vessels in the zygoma. The
      zygomatic bone is a safe intraoral donor site for the reconstruction of small- to
      medium-sized alveolar defects.

PMID- 15556329
TI  - Vascularization of the peroneal muscles. Critical evaluation in fibular free flap
      harvesting.
AB  - This anatomical study was carried out in order to discover the etiology of
      partial necrosis of the peroneus longus and brevis muscles after fibular
      osteocutaneous flap harvest. The vascular supply to the lateral compartment
      peroneal muscles was investigated in 10 fresh cadaveric lower limbs. The peroneal
      muscles are supplied by two principal sources arteries, the anterior tibial
      artery (ATA) and the peroneal artery (PA). The ATA is the dominant artery and
      supplies the proximal and middle thirds of these muscles. The PA is considered to
      be a supplementary vascular source and supplies the distal thirds of these
      muscles. After harvesting the PA in a fibular flap, regions of the peroneal
      muscles preoperatively vascularized by its branches become supplied through the
      anastomotic "choke" vessels between the ATA and the PA. Primary closure of the
      cutaneous defect increases the possibility of developing a pseudo-compartment
      syndrome with necrosis of the more precariously vascularized portions of the
      peroneal muscles. This complication is difficult to diagnosis early and the
      reason why we advocate that direct skin closure following composite harvest must
      be avoided. Moreover, conservation of the inferior and superior lateral branches
      of the ATA is imperative in order to preserve the peroneal muscles
      vascularization.

PMID- 15556330
TI  - Malignant pleural mesothelioma metastasis to the mandible.
AB  - Malignant mesothelioma is a rare tumor arising from the pleura or peritoneum.
      Distant hematogenous metastasis is seen in more than half of cases,
      preferentially to the brain, lung, bone and soft tissues [Br. J. Dis. Chest 70
      (1976) 246]. There has been only one previous report of this tumor metastasizing
      to the jaw bone [Pathologica 92 (2000) 273].

PMID- 15556331
TI  - Primary non-Hodgkin's lymphoma of the mandible. Report of a case.
AB  - A case of a 45-year-old white man admitted for an osteomyelitis and subsequently
      diagnosed affected by an IE stage, diffuse high grade large B cell non-Hodgkin's
      lymphoma of the mandible is reported. The patient presented a swelling in the
      right mandibular region with paraesthesia of the ipsilateral lower lip without
      nodal involvement of the neck. After an incisional biopsy, which showed a diffuse
      high grade large B-cell non-Hodgkin's lymphoma, the patient was staged and
      treated with CEOP protocol for six courses and subsequently external beam
      radiation therapy with complete remission of the lesion.

PMID- 15556332
TI  - Eruption cyst in the adult--a case report.
AB  - A case of eruption cyst in the right maxilla of a 40-year-old female is reported.

PMID- 15556333
TI  - Primary mandibular bone xanthoma. A case report.
AB  - We describe a case of a xanthoma located in the mandible of an 11-year-old boy.
      The lesion, apparently benign, did not produce pain. It did, however, produce
      mandibular expansion by infiltration. In jaws, xanthoma has been very rare; in
      order to diagnose primary xanthoma, it was necessary to discount other
      histological entities or the association of hyperlipoproteinemia. Treatment was
      the total excision of the lesion.

PMID- 15556334
TI  - Sialosis and necrotising sialometaplasia in bulimia; a case report.
AB  - Salivary gland involvement, particularly salivary gland enlargement (sialosis),
      is a recognised complication in bulimia. We report the rare association of
      sialosis and necrotising sialometaplasia with bulimia in the same patient. The
      association of sialosis and necrotising sialometaplasia in the same patient with
      bulimia has been reported previously in two patients and may be coincidental, but
      the appearance in this additional patient suggests it may be prudent to explore
      this further.

PMID- 15556335
TI  - Bone grafts for jaw augmentation procedures: anterior versus posterior iliac
      crest.

PMID- 15556338
TI  - Trichosanthin's interfacial interactions with phospholipids: a monolayer study.
AB  - Lipid monolayer at the air/water interface, as half a membrane, was used here to
      investigate the interaction between trichosanthin (TCS), a ribosome inactivating
      protein, and phospholipid membrane. First, the protein adsorption experiments
      showed that the negatively charged DPPG caused obvious enrichment of TCS beneath
      the monolayer, indicating electrostatic attraction between TCS and the negatively
      charged phospholipid. Second, when TCS was incorporated into the phospholipid
      monolayer, it could not be completely squeezed out until the monolayer collapsed.
      The results were demonstrated to be irrelative with the phospholipid headgroup,
      suggesting a strong hydrophobic force between TCS and phospholipid hydrocarbon
      chain was involved in the interaction. Third, the protein/membrane interaction
      was further studied with fluorescence microscope. The results showed that TCS
      could penetrate into both the condensed and the fluid phase of the DPPG monolayer
      under low pH condition and eventually resulted in a homogeneous phospholipid
      phase. The breakage of ordered packing of phospholipid by TCS may be responsible
      for this homogenizing effect.

PMID- 15556339
TI  - Effect of amphiphilic molecules upon chromatic transitions of polydiacetylene
      vesicles in aqueous solutions.
AB  - Effect of amphiphilic molecules upon the chromatic transitions of polymerized
      10,12-pentacosadiynoic acid (PCDA) vesicles in aqueous solutions was reported.
      The colorimetric response of polymerized PCDA vesicles for 1-pentanol is higher
      than that for ethanol due to more hydrophobic property of 1-pentanol. The
      colorimetric response of polymerized PCDA vesicles for sodium dodecyl sulfate
      (SDS) and Triton X-100 is lower than that for cetyltrimethylammonium bromide
      (CTAB). The strong ability of CTAB to induce chromatic transition of the vesicles
      is related to the positively charged headgroups of CTAB, which favors approach of
      CTAB to the negatively charged carboxylate groups at the vesicle surface. The
      insertion of alkyl chain of CTAB into the hydrophobic domain perturbs the
      conformation of the conjugated polymer backbone and induces color change of
      polydiacetylene vesicles. For a series of alkylamine hydrochloric salts, the
      longer the alkyl chain, the stronger the ability of alkylamine to induce
      chromatic transition of polydiacetylene vesicles.

PMID- 15556340
TI  - Surfactant layering on mixed monolayer-protected gold clusters.
AB  - Positively-charged monolayer protected gold clusters (MMPCs) were mixed with
      sodium dodecyl sulfate (SDS). At lower SDS concentration, the initially water
      soluble particles became organic-soluble while remaining discrete. Upon further
      addition of SDS, the particles aggregate and become water-soluble. NaCN
      decomposition, TEM, and DLS characterization reveal the morphology and properties
      of these encapsulated assemblies.

PMID- 15556341
TI  - Nano-fibrous scaffolds for tissue engineering.
AB  - With the ability to form nano-fibrous structures, a drive to mimic the
      extracellular matrix (ECM) and form scaffolds that are an artificial
      extracellular matrix suitable for tissue formation has begun. These nano-fibrous
      scaffolds attempt to mimic collagen, a natural extracellular matrix component,
      and could potentially provide a better environment for tissue formation in tissue
      engineering systems. Three different approaches toward the formation of nano
      fibrous materials have emerged: self-assembly, electrospinning and phase
      separation. Each of these approaches is very different and has a unique set of
      characteristics, which lends to its development as a scaffolding system. For
      instance, self-assembly can generate small diameter nano-fibers in the lowest end
      of the range of natural extracellular matrix collagen, while electrospinning has
      only generated large diameter nano-fibers on the upper end of the range of
      natural extracellular matrix collagen. Phase separation, on the other hand, has
      generated nano-fibers in the same range as natural extracellular matrix collagen
      and allows for the design of macropore structures. These attempts at an
      artificial extracellular matrix have the potential to accommodate cells and guide
      their growth and subsequent tissue regeneration.

PMID- 15556342
TI  - Biomaterials in total joint replacement.
AB  - The current state of materials systems used in total hip replacement is presented
      in this paper. An overview of the various material systems used in total hip
      replacement reported in literature is presented in this paper. Metals, polymers,
      ceramics and composites are used in the design of the different components of hip
      replacement implants. The merits and demerits of these material systems are
      evaluated in the context of mechanical properties most suitable for total joint
      replacement such as a hip implant. Current research on advanced polymeric
      nanocomposites and biomimetic composites as novel materials systems for bone
      replacement is also discussed. This paper examines the current research in the
      materials science and the critical issues and challenges in these materials
      systems that require further research before application in biomedical industry.

PMID- 15556343
TI  - Biocatalysis in the development of functional polymer-ceramic nanocomposites.
AB  - Fluorescent silica/polymer nanocomposites have been synthesized by condensing
      tetramethyl orthosilicate (TMOS) around fluorescent polymer strands of poly(2
      naphthol). The polymer is biocatalytically synthesized via peroxidase catalyzed
      polymerization in micelles of the cationic surfactant, cetyltrimethylammonium
      bromide (CTAB). Silica condensation at the micelle-water interface results in
      encapsulation of the polymer. Fluorescence spectroscopy and fluorescent light
      microscopy provide critical evidence that the polymer luminescence properties are
      conferred to the composite material. The fabrication of polymer entrapped in
      ordered, mesoporous materials represents a viable step toward the development of
      functional polymer-ceramic nanocomposites.

PMID- 15556344
TI  - Proceedings of the First Congress on Synthetic Receptors. October 15-17, 2003.
      Lisbon Portugal.

PMID- 15556345
TI  - Monitoring of cAMP-imprinted polymer by fluorescence spectroscopy.
AB  - Conventional functional monomers together with fluorescent monomer, trans-4-[p
      (N,N-dimethylamino)styryl]-N-vinylbenzylpyridinium chloride (vb-DMASP), were
      copolymerised in the presence of a target molecule, nucleotide-cAMP that acted as
      a molecular template. The polymer was copolymerised in thin-layer films. After
      removal of the template the functionalised cavities that exist in the fluorescent
      material are able to specifically bind the template. Subsequent adsorption of the
      template-cAMP causes quenching of fluorescence of the polymer. The specific
      photochemical processes accompanying the template adsorption are discussed
      further. The imprinted polymers monitored by both steady-state and time-resolved
      fluorescence techniques show specificity and selectivity of binding of the
      template on the imprinted functionalised cavities.

PMID- 15556346
TI  - Synthetic receptors for chemical sensors--subnano- and micrometre patterning by
      imprinting techniques.
AB  - Antibody-like selectivities are introduced into man-made polymeric systems by
      means of molecular imprinting. On the molecular scale, organic contaminants in
      water were analysed by 10 MHz QCM sensors coated both with affinity layers and
      with selective imprinted polymers. Affinity layers, polystyrene/silicone, yield
      sensor effects for aromatic hydrocarbons according to, e.g., molecular weight and
      solubilities, a prediction by molecular modelling is proposed. Imprinted layers,
      however, recognise molecular shapes: the lean toluene is favoured by factor of
      six to the more bulky o-xylene; even the three xylenes can be distinguished from
      each other. On the micrometre scale, erythrocytes of different blood groups are
      differentiated, although their geometrical shape is identical. In this case, the
      recognition is accomplished by a predefined hydrogen bonding network between
      excess OH groups of the polyurethane layer and the sugar molecules on the cell
      surface defining the blood group.

PMID- 15556347
TI  - The use of molecularly imprinted sol-gels in pharmaceutical separations.
AB  - This paper illustrates the potential of the sol-gel process to imprint the
      pharmaceutical active--N-[N-[(1S)-1-carboxssy-3-phenylpropyl]-l-lysyl]-L-proline,
      (lisinopril dihydrate). This template exhibits unique difficulties such as
      limited solubility in non-polar and most polar porogens with multiple
      functionality evident in its 4 pKa values. Selectivity for this template was
      achieved using a 3-monomer sol-gel system utilising solid phase extraction (SPE).
      Analysis of the template and its related substances was achieved using HPLC. The
      effect of solvent polarity on the rebinding of the template was studied. Through
      optimisation of porogen and extraction solvent, the imprinted material (MIP)
      demonstrated enhanced selectivity, for the template, over a non-imprinted
      material (NIP). Selectivity was also illustrated for the original template over
      two of its related substances. The effect of starting monomer ratio on
      selectivity was studied to determine the interactions, which could best be
      exploited to further enhance selectivity.

PMID- 15556348
TI  - The interaction of azacrown ether with fatty acid in nonpolar solvents and at the
      organic-aqueous interface.
AB  - In the paper, we show that lipophilic azacrown ether (22DD) in solvents of low to
      intermediate polarity forms the complexes with fatty acids, like lauric or
      palmitic acid. Due to the weak acid-base properties of the azacrown ether-fatty
      acid system, no proton transfer between the two molecules was observed, as shown
      by IR and 1H NMR studies. The Job plot exhibits double maximum, suggesting the
      coexistence of two 22DD-fatty acid complexes, of 1:1 and 1:2 stoichiometry,
      respectively. Their stability constants were calculated by taking into account
      the dimerization of fatty acid in toluene. The diffusion coefficients for the
      free molecules and their complexes were measured with diffusion-ordered
      spectroscopy (DOSY) NMR in order to prove the close spatial proximity of the
      molecules. Interfacial tension measurements at the water-toluene interface showed
      that due to the presence of two decyl chains, 22DD adsorbs at the interface much
      stronger than dodecanoic (lauric) acid does. The shape of the adsorption isotherm
      for the mixture of 22DD and lauric acid suggests that the two molecules also
      interact at the interface in a similar manner as in the bulk of low to
      intermediate polarity solvents. As a result of the affinity of the fatty acid to
      strongly surface-active azacrown ether, the interface might be enriched with
      fatty acid molecules, which without 22DD shows little adsorption at the liquid
      liquid interface.

PMID- 15556349
TI  - Effect of the solvent on recognition properties of molecularly imprinted polymer
      specific for ochratoxin A.
AB  - A molecularly imprinted polymer specific for the mycotoxin ochratoxin A has been
      synthesised using a non-covalent approach. The polymer has shown an excellent
      affinity and specificity for the target template in aqueous solutions. The
      binding experiments, NMR study and molecular modelling have proven that the
      template recognition by polymer originates from the shape complementarity of
      binding sites. The binding mechanism is critically depended on factors that
      affect the polymer conformation. Thus the variation in buffer concentration, pH
      and presence of organic solvent, which affect the polymer swelling or shrinking,
      had a profound effect on the polymer recognition properties.

PMID- 15556350
TI  - A molecularly imprinted catalyst designed by a computational approach in
      catalysing a transesterification process.
AB  - A computational approach was developed to optimize the monomer formulation of
      molecularly imprinted catalysts. A virtual library of the intermediates of a
      lipase-catalysed transesterification process was constructed using Chem3D
      software with p-nitrophenyl acetate as substrate. The energies of the
      intermediates were minimized using the semi-empirical MOPAC method with the most
      stable intermediate expected to lead to a higher turn over rate. According to the
      optimization results, a MIC was prepared by co-polymerising 4(5)-vinylimidazole
      and itaconic acid with trimethylpropanol trimethacrylate micro spheres in the
      presence of p-nitrophenyl acetate. The MIC achieved of the transesterification
      process between p-nitrophenyl acetate and hexanol with a turn over rate of 26.2
      min(-1), and showed substrate specificity towards its template with a 6.5-fold
      preference for p-nitrophenyl acetate over p-nitrophenyl salicylate.

PMID- 15556351
TI  - Molecularly imprinted polypyrrole-based synthetic receptor for direct detection
      of bovine leukemia virus glycoproteins.
AB  - Preparation and basic characterization of polypyrrole-based molecularly imprinted
      polymer (MIP) for label-free detection of bovine leukemia virus (BLV)
      glycoprotein gp51 (gp51) is firstly described. Polypyrrole (Ppy) was selected as
      a matrix for preparation of MIP. Polypyrrole doped by gp51 (gp51/Ppy) was
      prepared by electrochemical deposition of this polymer on the surface of platinum
      black electrode. Then, molecules of gp51 were removed from polymeric backbone and
      molecularly imprinted polypyrrole (mPpy) was ready for recognition of gp51 in the
      aqueous solution. Pulsed amperometric detection (PAD) was applied for label-free
      detection of gp51 in the samples. Anti-gp51 antibodies and secondary antibodies
      labeled with horseradish peroxidase (HRP) were involved as markers for the
      control of mPpy preparation procedures. Control experiments were also
      simultaneously performed by spectrophotometrical detection of HRP activity.
      Application of anti-gp51 and HRP labelled secondary antibodies confirmed that
      generation of analytical signal was based on redoping of mPpy by gp51. During our
      experiments, only few mPpy redoping/dedoping cycles were effective, but generally
      this method seems to be very effective for the future development of mPpy-based
      MIPs. Preparation, electrochemical investigation and control procedures are
      described in the current paper.

PMID- 15556352
TI  - Acrylic polymeric nanospheres for the release and recognition of molecules of
      clinical interest.
AB  - Cross-linked poly(methylmethacrylate-co-methacrylic acid) nanospheres were
      imprinted with theophylline through template radical polymerisation in diluted
      acetonitrile solution. This study will focus on the effect of functional monomer
      nature used (methylmethacrylate and/or methacrylic acid) in the recognition and
      in the release of template in order to develop a material with combined
      properties of drug delivery and rebinding for clinical applications. After
      template extraction the nanospheres showed satisfactory recognition properties
      (up to 1mg template/g of polymer). Moreover polymers prepared selectively removed
      theophylline with a theophylline rebinding of 5.1 times higher than that of
      caffeine, a compound of similar structure. Drug release properties were also
      satisfactory (up to 95% of loaded theophylline in 7 days).

PMID- 15556353
TI  - Imprinted polymer layer for recognizing double-stranded DNA.
AB  - A method of preparing a thin polymer layer able to recognize double-stranded DNA
      (dsDNA) was developed by using 2-vinyl-4,6-diamino-1,3,5-triazine (VDAT) as a
      functional monomer for creating a DNA-imprinted polymer. The formation of
      hydrogen bonds between VDAT and A-T base pairs in dsDNA was confirmed by
      measuring the effects of VDAT on the melting point and the NMR and CD spectra of
      dsDNA. An imprinted polymer that can recognize dsDNA of the verotoxin gene was
      prepared by polymerizing VDAT, acrylamide, a crosslinking agent, and the template
      verotoxin dsDNA on a silanized glass surface. The specificity of this polymer
      layer for binding verotoxin dsDNA was investigated by using fluorescent-labelled
      dsDNAs. The fluorescence intensity of the polymer layer after binding verotoxin
      dsDNA was twice as high as after binding oligo(dG)-oligo(dC), indicating that
      verotoxin dsDNA was preferentially bound to the polymer imprinted with verotoxin
      dsDNA. The kinetics of verotoxin dsDNA binding to the imprinted polymer were
      analyzed by surface plasmon resonance measurements. The dissociation constant
      (KD) was low, of the order of 10(-9)M.

PMID- 15556354
TI  - A direct comparison of the performance of ground, beaded and silica-grafted MIPs
      in HPLC and turbulent flow chromatography applications.
AB  - Spherical molecularly imprinted polymers (MIPs) specific to the beta-blocker
      propranolol have been synthesised using two different approaches and compared to
      traditional ground monolithic MIPs in HPLC and TFC applications. TFC is a LC
      technique used for rapid extraction of compounds directly from complex matrices.
      It can be easily coupled to HPLC and MS for automation of an extraction/analysis
      procedure. Spherical MIP beads were produced using a suspension polymerisation
      technique and silica/MIP composite beads by grafting MIP to spherical silica
      particles using a surface-bound initiator species. Synthesis of both beaded and
      silica-grafted MIPs was more practical than using the traditional grinding method
      and yields of spherical particles of the required size between 80 and 100% were
      routinely achieved. Under HPLC conditions, beaded and ground MIP materials showed
      a degree of chiral separation for all of the nine beta-blockers tested. The
      beaded MIP, however, showed much better flow properties and peak shape than the
      ground material. Silica-grafted MIP showed some separation in five of the drugs
      and a large improvement in peak shape and analysis times compared with both
      ground and beaded MIPs. The materials prepared were also used in extraction
      columns for Turbulent Flow Chromatography (TFC). Although no imprinting effect
      was observed under typical TFC conditions, beaded polymer materials showed
      promise for use as TFC extraction columns due to the good flow properties and
      clean extracts obtained.

PMID- 15556355
TI  - Electronic transduction in model enzyme sensors assisted by a photoisomerizable
      azo-polymer.
AB  - We develop a stochastic model of electronic transduction by means of a rod-like
      azo-polymer (single peptide molecule doped with a given amount of azo-benzene
      structural units) in polymer-redox enzyme biosensor. We propose a configuration
      where the azo-polymer is anchored next to the enzyme reaction center and
      functions as a light-driven micromechanical actuator shuttling electrons toward
      the electrode. We show that the output catalytic current is exponentially
      sensitive to variations in geometrical size of the polymer (a 'switch off'
      effect) and suggest a scheme where the switching effect is triggered by polymer
      photoisomerization, resulting in its overall length change.

PMID- 15556356
TI  - Design of an amperometric biosensor using polypyrrole-microgel composites
      containing glucose oxidase.
AB  - A new material consisting of a water-dispersed complex of polypyrrole
      polystyrensulfonate (PPy) embedded in polyacrylamide (PA) has been prepared and
      tested as enzyme immobilizing system for its use in amperometric biosensors.
      Glucose oxidase (GOx) and the water-dispersed polypyrrole complex were entrapped
      within polyacrylamide microgels by polymerization of acrylamide in the dispersed
      phase of concentrated emulsions containing GOx and PPy. Polymerization of the
      dispersed phase provides microparticles whose size lies between 3.5 and 7 microm.
      The aim of incorporating polypyrrole into the polyacrylamide microparticles was
      to facilitate the direct transfer of the electrons released in the enzymatic
      reaction from the catalytic site to the platinum electrode surface. The
      conductivity of the microparticles was measured by a four-point probe method and
      confirmed by the successful anaerobic detection of glucose by the biosensor.
      Thus, the polyacrylamide-polypyrrole (PAPPy) microparticles combine the
      conductivity of polypyrrole and the pore size control of polyacrylamide. The
      effects of the polyacrylamide-polypyrrole ratio and cross-linking on the
      biosensor response have been investigated, as well as the influence of analytical
      parameters such as pH and enzymatic loading. The PAPPy biosensor is free of
      interferences arising from ascorbic and uric acids, which allows its use for
      quantitative analysis in human blood serum.

PMID- 15556357
TI  - Acetylcholinesterase-based biosensor electrodes for organophosphate pesticide
      detection. I. Modification of carbon surface for immobilization of
      acetylcholinesterase.
AB  - Screen-printed carbon electrodes modified with the dialdehydes, glutaraldehyde
      and terephthaldicarboxaldehyde, and then polyethyleneimine have been utilized for
      production of pesticide biosensors based on acetylcholinesterase. To improve the
      extent of dialdehyde modification, the electrodes were NH2-derivatized, initially
      by electrochemical reduction of 4-nitrobenzenediazonium to a nitroaryl radical
      permitting attachment to the carbon surface. Subsequent reduction of the 4
      nitrobenzene yields a 4-aminobenzene modified carbon surface. Drosophila
      melanogaster acetylcholinesterase was immobilized either covalently onto
      dialdehyde modified electrodes or non-covalently onto polyethyleneimine modified
      electrodes. Internal diffusion limitations due to the dialdehyde and
      polyethyleneimine modifications increased the apparent Km of the immobilized
      enzyme. The thiocholine sensitivity was about 90% for dialdehyde modified
      electrodes and about 10% for polyethyleneimine modified electrodes as compared
      with non-modified carbon electrodes. The detection limit of the biosensors
      produced by non-covalent immobilization of acetylcholinesterase onto
      polyethyleneimine modified carbon electrodes was found to be about 10(-10) M for
      the organophosphate pesticide dichlorvos.

PMID- 15556358
TI  - Study of mixed Langmuir-Blodgett films of immunoglobulin G/amphiphile and their
      application for immunosensor engineering.
AB  - Langmuir-Blodgett (LB) technique appears to be quite suitable for generating
      biospecific surfaces and it has potential application for fabricating biosensors.
      In this work, mixed Langmuir-Blodgett films of immunoglobulin G/amphiphile have
      been transferred onto hydrophobic silver surface previously modified by 1
      octadecanethiol (ODT) SAMs. In order to obtain stable LB films, the influences of
      different parameters - type of amphiphile, surface pressure and pH - on the
      properties of mixed IgG/amphiphile monolayer, were investigated. Electrochemical
      properties of the engineered immunosensor have been measured by impedimetric
      spectroscopy. The immunosensor obtained exhibits a high sensitivity and a good
      specificity in a linear dynamic range from 200 to 1000 ng ml(-1).

PMID- 15556359
TI  - Evaluation of a high-affinity QCM immunosensor using antibody fragmentation and 2
      methacryloyloxyethyl phosphorylcholine (MPC) polymer.
AB  - This study evaluated construction of a highly affinitive quartz crystal
      microbalance (QCM) immunosensor using anti-C-reactive protein (CRP) antibody and
      its fragments for CRP detection. Three types of antibody were immobilized on the
      surface of a QCM via covalent-bounding. Then affinity was evaluated through
      antigen-antibody binding between CRP and its antibody. Affinity between antigen
      antibody was shown to be highest when anti-CRP F(ab')2-IgG antibody (70
      microg/mL) was immobilized on the QCM. In case of anti-CRP F(ab')2-IgG antibody,
      affinity which was attributable to antigen-antibody binding was almost twice that
      of anti-CRP IgG antibody, which is used conventionally for QCM immunosensors. In
      addition, when it was treated with 2-methacryloyloxyethyl phosphorylcholine-co-n
      butyl methacrylate, so-called MPC polymer, highly affinitive and selective
      immunosensing for CRP was achieved without non-specific binding from plasma
      proteins in human serum. When anti-CRP F(ab')2-IgG antibody was immobilized on
      the QCM, the detection limit and the linearity of CRP calibration curve were
      achieved at concentrations from 0.001 to 100 microg/dL even during investigation
      in serum samples. Experimental results verified the successful construction of a
      highly affinitive and selective QCM-immunosensor which was modified with anti-CRP
      F(ab')2-IgG antibody and MPC polymer.

PMID- 15556360
TI  - Liquid phase SPR imaging experiments for biosensors applications.
AB  - Surface plasmon resonance (SPR) has recently gained attention as a label-free
      method for the detection of biological molecules binding onto functionalised
      surfaces. It is one of the most sensitive detection method for monitor variations
      in the thickness and refractive index in ultra-thin films. Here, the adsorption
      processes of oligonucleotides onto gold substrates have been investigated in
      aqueous buffer solution using SPR imaging measurements. The hybridization of a
      thiol-modified, single stranded oligonucleotide anchored to a gold surface via
      thiol group, with its complementary sequence has been observed and characterised
      monitoring the hybridization process by SPR equipment. In situ investigation of
      smallest changes in SPR imaging measurements dynamically performed in liquid
      phase in the presence of DNA complementary probes was performed. Infrared
      spectroscopy and scanning electron microscopy characterisation of the
      functionalised gold surfaces of the biosensor were compared with the images
      obtained by SPR experimental apparatus.

PMID- 15556361
TI  - Development of biosensors with aptamers as bio-recognition element: the case of
      HIV-1 Tat protein.
AB  - The in vitro selection of combinatorial libraries of RNA/DNA, has allowed the
      identification of specific nucleic acids (aptamers) which bind to a wide range of
      target molecules with high affinity and specificity. In this work, an RNA
      aptamer, specific for the protein trans-activator of transcription (Tat) of HIV
      1, has been used as bio-recognition element to develop a biosensor (aptasensor).
      The biosensor was optimised using piezoelectric quartz-crystals as transducers
      and the aptamer was immobilised on the gold electrode of the crystal. The
      immobilisation procedure was based on the interaction between the biotinylated
      aptamer and streptavidin previously deposited on the electrode. The main
      analytical characteristics of the biosensor, such as sensitivity, selectivity and
      reproducibility, have been studied in details. An optimised regeneration
      procedure allowed the multiple use of the aptamer-coated crystal. The aptasensor
      has been compared with the corresponding immunosensor, based on the specific
      monoclonal anti-Tat antibody. The antibody was immobilised on a layer of
      carboxylated dextran previously deposited on the gold electrode. The results
      demonstrated that the use of a biosensor with a specific aptamer as bio
      recognition element could be an interesting approach in the detection of
      proteins, which has been here examined considering a model system.

PMID- 15556362
TI  - Receptor-mediated biological responses are prolonged using hydrophobized ligands.
AB  - Hormone-receptor interactions occur following three-dimensional diffusion of the
      ligand to the membrane-embedded receptor. However, prior hydrophobization of the
      ligand might restrict its movement to two dimensions along the membrane surface,
      and the biological response might therefore be modulated. This idea was tested
      using the C-terminal nonapeptide, CCK9, of the satiating hormone, cholecystokinin
      (CCK). The hormone was lipidated by linking it covalently to
      distearoylphosphatidylethanolamine via a poly(ethylene glycol) (PEG) spacer. The
      desired conjugate was isolated by thin-layer chromatography and incorporated into
      preformed small unilamellar dimyristoylphosphatidylcholine (DMPC) vesicles. The
      hormone-bearing vesicles were injected intraperitoneally into Wistar rats and
      food intake monitored. Compared to the biological effect elicited by the same
      amount of soluble non-derivatized CCK9, food intake reduction showed a delayed
      onset, but lasted for a significantly longer time. We believe this prolonged
      effect was due to the transfer of the derivatized CCK9 from the vesicles to the
      natural membrane containing the hormone receptor. Ultimately, this event may
      result in sustained receptor occupation and, thus, food intake reduction. The
      underlying mechanism for the physiological effects observed may be of relevance
      in interpreting results obtained using artificial measuring devices; for example,
      the signal produced by biosensors may be drastically affected by the
      hydrophobicity of the ligand.

PMID- 15556363
TI  - Synthesis of tethered-polymer brush by atom transfer radical polymerization from
      a plasma-polymerized-film-coated quartz crystal microbalance and its application
      for immunosensors.
AB  - This study synthesizes a tethered surface-grafted poly(acrylic acid) with quartz
      crystal microbalance (QCM) surfaces and provides detailed analysis of their
      properties and application. A tethered polyelectrolyte brush of poly(acrylic
      acid) is generated by first covering the substrate with a plasma-polymerized
      allyl alcohol (pp-AA) film, changing the polymerization initiators (bromination),
      and then grafting through atom transfer radical polymerization (ATRP) of tert
      butyl acrylate (t-BA); these initiators are immobilized on a surface and exposed
      to a monomer. Finally, we convert the poly(t-BA) brush into poly(acrylic acid)
      through hydrolysis. We use the QCM technique to measure configuration change of
      the tethered poly(acrylic acid) grafted chains with two different degrees of
      polymerization (DP=50,200) in aqueous solutions at three different pH values
      (4.0, 4.8, and 5.4). The tethered poly(acrylic acid) grafted QCM shows that
      repeatable frequency responses are induced by pH change of solution. These
      frequency responses of large DP for pH are 20 times larger than responses of
      lower DP for pH. The frequency response of antibody immobilization on tethered
      poly(acrylic acid) grafted QCM (DP=200) and its frequency response of
      immunoreaction are 10 times larger than conventional immobilization methods by
      cysteamine with glutalaldehyde coupling of the antibody. The tethered
      poly(acrylic acid) grafted QCM can increase the frequency response for pH, the
      immobilization amount of antibody, and immunosensor response.

PMID- 15556364
TI  - Sorption of amines by the Langmuir-Blodgett films of soluble cobalt
      phthalocyanines: evidence for the supramolecular mechanisms.
AB  - By means of microgravimetry, UV-Vis spectroscopy and optic microscopy, sorption
      of pyridine, primary aliphatic amines and benzylamine by the Langmuir-Blodgett
      (LB) films of tetra-4-tert-butyl- and tetra-(3-nitro-5-tert-butyl)-substituted
      cobalt phthalocyanines (CoPc' and CoPc*, respectively) was studied over a broad
      concentration range. In general, sorption occurs as stepwise intercalation of the
      sorbate molecules into the supramolecular 3D structure of the phthalocyanine
      assembly followed by formation of the donor-acceptor complexes. Both
      intercalation depth and stoichiometry of the complexes are determined by the
      molecular structure of amines. The supramolecular factor allows discrimination
      between amines in air but not in aqueous solutions because of concurrent
      intercalation of water.

PMID- 15556365
TI  - A molecular recognition strategy towards tetra-chlorinated dibenzo-p-dioxins,
      TCDDs.
AB  - Uniformly sized polymeric separation media were prepared using o- or p-xylene as
      porogenic template to investigate chromatographic selectivity towards tetra
      chlorinated dibenzo-p-dioxins (TCDDs). TCDDs having chlorine atoms at ortho
      positions of phenyl rings were selectively retained on stationary phase prepared
      with o-xylene as porogenic template, while TCDDs having chlorine atoms at para
      positions of phenyl ring were found to be retained selectively on the stationary
      phase imprinted by the porogenic template, p-xylene. Slightly longer cross
      linking agent afforded chromatographically selective retention for larger TCDD
      isomers. It was also found that positional relationship between substituted
      chlorine atoms was also important for chromatographic recognition.

PMID- 15556366
TI  - Piezoelectric sensor functionalised by a self-assembled bipyridinium derivative:
      characterisation and preliminary applications in the detection of heavy metal
      ions.
AB  - The synthesis of a molecule, 1-(11-dodecylsulfanyl-undecyl)-[4,4']bipyridinium
      bromide (1), suitable at the same time to form a covalent bond with gold
      electrodes of a piezoelectric quartz crystal and to interact with heavy metal
      ions in aqueous solutions, has been successfully accomplished. A commercial
      quartz crystal microbalance instrument has been modified in order to perform a
      Flow-Injection Analysis. The behaviour of the system follows the Kanazawa-Gordon
      equation as demonstrated by measurements with glucose solutions. The self
      assembled layer of 1 onto a gold electrode has been characterised by Atomic Force
      Microscopy before and after the sensing tests. The sensing performances of the
      modified gold electrode were investigated by monitoring the frequency variation
      induced by the presence of heavy metal ions, such as lead, cadmium and mercury,
      in aqueous media. The explored concentrations ranged between 10(-4) and 10(-2) M
      and the corresponding frequency variations ranged between 10 and 50 Hz. All
      responses observed were fast, reproducible and reversible. In particular, the
      response to mercury appears significantly higher in comparison with the other
      analytes. To the best of our knowledge, this contribution represents the first
      example of sensing layer based on bipyridinium receptor showing reversible and,
      at some extent, differentiated response towards heavy metal ions.

PMID- 15556367
TI  - The fluorescence studies of the sol-gel transition by styrylpyridine derivative.
AB  - The gelation process of tetraethylorthosilanes in acid environment was monitored
      with the trans-4-(p-N,N-dimethylaminostyryl)-N-vinylbenzylopyridinium chloride
      (vbDMASP) fluorescent probe. The fluorescence steady-state and anisotropy
      measurements of material during sol-gel transition are reported. The results are
      compared with fluorescence studies of the probe in a modeled viscous system of
      water-glycerol mixtures. A strong increase of anisotropy, from 0.1 to 0.9, with
      gelation time as well with wavelength, was observed. Although the increase of
      anisotropy with wavelength is due to specificity of the compounds exhibiting
      charge transfer properties, the increase of the anisotropy with gelation time is
      due to an increase of microviscosity. On this basis, suitability of the applied
      fluorophore in recording of viscosity changes during sol-gel transition is
      discussed. The molecular structure of vbDMASP in the excited states in dependence
      on environmental polarity was optimized using the HyperChem and Amsol program.
      The dynamics of torsional angle C35-C34-N31-C28 of the multichromophore dye in
      correlation with micropolarity and microviscosity of the network formation during
      the sol-gel transition is discussed.

PMID- 15556368
TI  - Piezoelectric sensors for dioxins: a biomimetic approach.
AB  - The aim of this work was to design a fast, cheap and easy to use analytical
      system for dioxins. Piezoelectric sensors coupled with the pentapeptides as
      biomimetic traps (the receptors), selective for the dioxins, were used for the
      realisation of this analytical system. A methodology to select specific receptors
      among all possible pentapeptides randomly generated was represented by the use of
      molecular modelling software. Three peptides called later on A, B and C (A:[N]Asn
      Phe-Gln-Gly-Ile[C]; B:[N]Asn-Phe-Gln-Gly-Gln[C]; C:[N]Asn-Phe-Gln-Gly-Phe[C]),
      were selected and evaluated for their potential usage as artificial receptors in
      solid-gas analysis by using a quartz crystal microbalance (QCM) sensors array.
      The peptide sequences were functionalised by two terminal cysteine residues in
      order to achieve a covalent interaction with the QCM gold surface. A manganese
      porphyrin complex and two other pentapeptides, a pentaglutamine (pentapeptide D)
      and a pentalysine (pentapeptide E), were used as negative control sensors. The
      QCM sensors (A, B and C) gave a good linearity against different sample
      concentrations of the 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) and a
      mixture of dioxins. In particular, the selectivity against 2,3,7,8-TCDD was
      nicely correlated to the estimated binding energy of the receptors calculated by
      computational modelling. The cross-reactivity of the system was quantified using
      commercial polychlorinated biphenyls (PCBs) mixtures (dioxin-like compounds).

PMID- 15556369
TI  - An amperometric biosensor for polyphenolic compounds in red wine.
AB  - In the present work, a biosensor was developed with Laccase Coriolus Versicolor
      as the biological reconnaissance element immobilized on derivatized
      polyethersulphone membranes and applied to a Pt-Ag, AgCl US electrode base. Its
      application to several polyphenols usually found in red wine (caffeic acid,
      gallic acid, catechin, rutin, trans-resveratrol, quercetin and malvidin) was
      tested. It was observed that an amperometric response was obtained for catechin
      at +100 mV (versus Ag, AgCl) and caffeic acid at -50 mV in acetate buffer
      solutions (pH 4.5) having 12% ethanol. At pH 3.5 and +100 mV the biosensor was
      sensitive to both substrates and their response was additive. A limit of
      detection of 1.0 x 10(-6) M, linearity ranging from 2.0 to 14.0 x 10(-6) M, high
      sensitivity (0.0566 mAM(-1)) and reproducibility (R.S.D. <10%) were achieved for
      equimolar mixed solutions of catechin and caffeic acid. Under the same
      experimental conditions the other polyphenols tested individually did not yield
      any biosensor response. The application of the biosensor to red wine samples
      required a previous solid phase extraction for polyphenols enrichment. In fact,
      attempts to apply the biosensor in red wine using the "standard addition"
      methodology showed that large interferences occurred, as was to be expected.
      Reduction currents of -0.33 +/- 0.03 nA were obtained when the biosensor was used
      with the wine extract at +100 mV. This current could be ascribed to catechin and
      caffeic acid, although some interference by other polyphenols at the matrix level
      seemed to persist. The present biosensor showed promising applications for the
      wine analysis in future.

PMID- 15556370
TI  - Wiring of PQQ-dehydrogenases.
AB  - The performance of pyrroloquinoline quinone (PQQ) dependent alcohol dehydrogenase
      (ADH) and two types of PQQ-glucose dehydrogenases in solution and when
      immobilized on the carbon paste electrodes modified with ferrocene derivatives is
      investigated. The immobilization of ADH consisting of PQQ and four hemes improves
      its stability up to 10 times. Both PQQ and heme moieties are involved in the
      electron transport from substrate to electrode. The ferrocene derivatives improve
      the electron transport 10-fold. Membrane-bound alcohol dehydrogenase from
      Gluconobacter sp. 33, intracellular soluble glucose dehydrogenase from
      Acinetobacter calcoaceticus L.M.D. 79.41 (s-GDH), and the membrane-bound enzyme
      (m-GDH) from Erwinia sp. 34-1 were purified and investigated. Soluble and
      membrane-bound PQQ-glucose dehydrogenases display different behavior during the
      immobilization on the modified carbon electrodes. The immobilization of s-GDH
      leads to a decrease in both stability and substrate specificity of the enzyme.
      This suggests that PQQ dissociates from the enzyme active center and operates as
      a free-diffusing mediator. The rate-limiting step of the process is likely the
      loading of PQQ onto the apo-enzyme. The immobilization of m-GDH leads to its
      substantial stabilization and improves the substrate specificity. The nature of m
      GDH binding to the electrode surface is presumably similar to the binding to the
      cell membrane through its anchor-subunit. The enzyme operates as an enzyme and
      mediator complex.

PMID- 15556371
TI  - Pt based enzyme electrode probes assembled with Prussian Blue and conducting
      polymer nanostructures.
AB  - Conductive polymer nanotubules of 1,2-diaminobenzene (1,2-DAB) were prepared
      using a porous polycarbonate membrane template, placed on a Pt foil and used to
      support the polymer, then, the electropolymerisation was performed by
      chronocoulometry. The obtained conductive polymer nanostructures were then placed
      on Pt electrode and used to support highly dispersed prussian blue (PB), which
      acts as the active component for H2O2 detection. The observed good stability of
      PB as catalyst of H2O2 was related to the presence of organic non-conventional
      conducting polymers in a composite nanostructured film. These nanostructured
      polymer/PB composite films were also characterised by scanning electron
      microscopy (SEM) and Raman spectroscopy. The non-conventional conducting polymer
      nanotubules/PB modified Pt electrodes were tested by cyclic voltammeter for
      stability at different pH values, then, by amperometry, for hydrogen peroxide,
      ascorbic acid, acetaminophen, uric acid and acetylcholine. Glucose oxidase (GOD),
      lactate oxidase (LOD), L-amino acid oxidase (L-AAOD), alcohol oxidase (AOD),
      glycerol-3-phosphate oxidase (GPO), lysine oxidase (LyOx), and choline oxidase
      (ChOx) were immobilised on PB layer supported on 1,2-diaminobenzene (1,2-DAB)
      nanotubules onto the Pt electrodes. Different strategies for enzyme
      immobilisation were performed and used. Analytical parameters such as
      reproducibility, interference rejection, response time, storage and operational
      stability of the sensors have been studied and optimised. Results provide a guide
      to design high sensitive, stable and interference-free biosensors. The glucose
      biosensors assembled with nanostructured poly(1,2-DAB) showed a detection limit
      of 5 x 10(-5) mol l(-1), a wide linearity range (5 x 10(-5) to 5 x 10(-3) mol l(
      1)), a high selectivity, a stability of 3 months at 4 degrees C, and at least 4
      weeks at room temperature. Similar analytical parameters and stability were also
      studied for L-(+)-lactic acid, L-leucine, ethanol, glycerol-3-phosphate, lysine,
      and choline biosensors.

PMID- 15556372
TI  - Bile acid amidoalcohols: simple organogelators.
AB  - Simple bile acid amide synthesis of lithocholic and deoxycholic acids with 2
      aminoethanol and 3-aminopropanol are reported. The structural properties of these
      amides were examined by NMR spectroscopic, ESI-TOF mass spectral, and X-ray
      crystallographic methods. The gelation properties of these amides in common
      organic solvents and in three different water solutions were also investigated
      using Tyndall effect, SEM, TEM, and optical microscopy. 2-Hydroxyethylamides were
      found to be effective gelators in chlorinated organic solvents and 3
      hydroxypropylamides in aromatic solvents. Both derivatives thicken neutral and
      acidic water solutions.

PMID- 15556373
TI  - Towards the design of host-guest complexes: biotin and urea derivatives versus
      artificial receptors.
AB  - Molecular mechanics calculations (Macromodel v.5.0 and v.8.1) have been used in
      order to correlate the minimized energies of the complexes with the binding
      constant Kb values measured on two hosts and five urea derivatives including
      methyl biotin. Kb values obtained by means of NMR titrations, in the right
      concentration range between 20 and 80% of saturation, correlate well with the
      energies provided by the molecular modeling study of the complexes.

PMID- 15556374
TI  - Molecular design of synthetic receptors with dynamic, imprinting, and allosteric
      functions.
AB  - Sugar recognition in an aqueous system has been achieved using a boronic acid
      diol interaction. Combination with an intramolecular amino group has enabled us
      to read out the binding process as a change in the fluorescence intensity. The
      novel interaction has been extended to dynamic sugar sensing utilizing an
      allosteric effect, molecular imprinting, and control of molecular assemblies.

PMID- 15556375
TI  - Snorenheit 911-searching for the 'truth' about snoring.

PMID- 15556376
TI  - The management of simple snoring.
AB  - Simple snoring is a very common problem that presents a number of different
      challenges. The initial difficulty is in confirming the presence of snoring, next
      one must exclude any other nocturnal respiratory pathology and finally a decision
      as to an appropriate treatment must be made. There are many different ways of
      achieving these objectives, but no one-way has a clear advantage in terms of both
      accuracy and cost effectiveness. In this review the authors do not intend to give
      a didactic method for the management of simple snoring but to discuss the pros
      and cons of various different options in order to help physicians make a choice
      based on local priorities.

PMID- 15556377
TI  - Treatment of snoring and obstructive sleep apnea with mandibular repositioning
      appliances.
AB  - Snoring and obstructive sleep apnea form part of a spectrum of sleep disordered
      breathing affecting a significant proportion of the general population and
      particularly the middle aged. The consequences can be severe and even life
      threatening for both the individual directly affected and those more remotely
      involved. Adverse sequelae can manifest themselves acutely or in the longer term
      as a result of obstructive breathing induced hypersomnolence, neurocognitive
      deficits and cardiovascular abnormalities. The combination of anatomical and
      neuromuscular risk factors in the pathogenesis of OSA has resulted in a varied
      approach to its management. One such treatment option is mandibular repositioning
      appliances (MRA), which mechanically stabilize the airway. Whilst the efficacy of
      this simple intervention has been rigorously proven quite recently in a
      significant proportion of patients with varying disease severity, individual
      patient selection in its application remains uncertain. Short-term side-effects
      are common but usually transient, whilst in the long-term minor permanent adverse
      developments on the dentition and occlusion have been reported. Considering both
      the medicolegal implications of snoring and OSA and the increasing popularity of
      MRA, it is recommended that skilled multidisciplinary respiratory and dental
      personnel form the primary care team.

PMID- 15556378
TI  - Obstructive sleep apnoea and anaesthesia.
AB  - Upper airway obstruction is common during both anaesthesia and sleep, as a result
      of loss of muscle tone present during wakefulness. Patients with obstructive
      sleep apnoea (OSA) are vulnerable during anaesthesia and sedation as the effects
      of loss of wakefulness are compounded by drug-induced depression of muscle
      activity and of arousal responses, so that they cannot respond to asphyxia.
      Conversely, those with 'difficult' airways during anaesthesia, either because of
      problems with maintenance of airway patency without tracheal intubation or
      because intubation itself is problematic, are at increased risk of OSA. These
      relationships have clinical importance. On the one hand identification of
      patients with OSA forewarns the anaesthetist of potential difficulty with airway
      maintenance intra- and postoperatively, influencing choice of anaesthetic
      technique and postoperative nursing environment. On the other hand difficulty
      with airway maintenance during anaesthesia should prompt further investigation
      for the possibility of OSA.

PMID- 15556379
TI  - State transitions between wake and sleep, and within the ultradian cycle, with
      focus on the link to neuronal activity.
AB  - The structure of sleep across the night as expressed by the hypnogram, is
      characterised by repeated transitions between the different states of vigilance:
      wake, light and deep non-rapid eye movement (NREM) sleep, and rapid eye movement
      (REM) sleep. This review is concerned with current knowledge on these state
      transitions, focusing primarily on those findings that allow the integration of
      data at cellular level with spectral time-course data at the encephalographic
      (EEG) level. At the cellular level it has been proposed that, under the influence
      of circadian and homeostatic factors, transitions between wake and sleep may be
      determined by mutually inhibitory interaction between sleep-active neurons in the
      hypothalamic preoptic area and wake-active neurons in multiple arousal centres.
      These two fundamentally different behavioural states are separated by the sleep
      onset and the sleep inertia periods each characterised by gradual changes in
      which neither true wake nor true sleep patterns are present. The results of
      sequential spectral analysis of EEG data on moves towards and away from deep
      sleep are related to findings at the cellular level on the generating mechanisms
      giving rise to the various NREM oscillatory modes under the neuromodulatory
      control of brainstem-thalamic activating systems. And there is substantial
      evidence at cellular level that transition to and from REM sleep is governed by
      the reciprocal interaction between cholinergic REM-on neurons and aminergic REM
      off neurons located in the brainstem. Similarity between the time-course of the
      REM-on neuronal activity and that of EEG power in the high beta range
      (approximately 18-30 Hz) allows a tentative parallelism to be drawn between the
      two. This review emphasises the importance of the thalamically projecting
      brainstem activating systems in the orchestration of the transitions that give
      rise to state progression across the sleep-wake cycle.

PMID- 15556380
TI  - Hot flashes and sleep in women.
AB  - Sleep disturbances during menopause are often attributed to nocturnal hot flashes
      and 'sweats' associated with changing hormone patterns. This paper is a
      comprehensive critical review of the research on the relationship between sleep
      disturbance and hot flashes in women. Numerous studies have found a relationship
      between self-reported hot flashes and sleep complaints. However, hot flash
      studies using objective sleep assessment techniques such as polysomnography,
      actigraphy, or quantitative analysis of the sleep EEG are surprisingly scarce and
      have yielded somewhat mixed results. Much of this limited evidence suggests that
      hot flashes are associated with objectively identified sleep disruption in at
      least some women. At least some of the negative data may be due to methodological
      issues such as reliance upon problematic self-reports of nocturnal hot flashes
      and a lack of concurrent measures of hot flashes and sleep. The recent
      development of a reliable and non-intrusive method for objectively identifying
      hot flashes during the night should help address the need for substantial
      additional research in this area. Several areas of clinical relevance are
      described, including the effects of discontinuing combined hormone therapy
      (estrogen plus progesterone) or estrogen-only therapy, the possibility of hot
      flashes continuing for many years after menopause, and the link between hot
      flashes and depression.

PMID- 15556381
TI  - Hormonal regulation of the fish gastrointestinal tract.
AB  - The gastrointestinal tracts (GIT) of fish and other vertebrates are challenged
      with a diversity of functional demands caused by changes and differences in
      dietary inputs and environmental conditions. This contribution reviews how
      hormonal regulation plays an essential role in modulating the GIT functions of
      fish to match changes in functional demands. Exemplary is how hormones produced
      by the GIT, the associated organs (e.g., pancreas), and other sources (e.g.,
      hypothalamus, adrenal cortex, thyroid, gonads) modulate the digestive processes
      (motility, secretion, and nutrient absorption) in response to dietary inputs.
      Hormones regulate the other GIT functions of osmoregulation (secretion and
      absorption of electrolytes and water), immunity, endocrine secretions,
      metabolism, and the elimination of toxic metabolites and environmental
      contaminants to match changes in environmental conditions and physiological
      states. Although the regulatory molecules and associated signaling pathways have
      been conserved during evolution of the vertebrate GIT, the specific responses
      often vary among fish with different feeding habits and from different
      environments, and can differ from those described for mammals.

PMID- 15556382
TI  - Gene expression, tissue distribution and potential physiological role of
      uncoupling protein in avian species.
AB  - Whole-body energy homeostasis and food intake control are essential for an
      economically sound selection for growth in poultry. The cellular and molecular
      mechanisms that regulate and link food intake, energy expenditure and energy
      balance are still poorly understood in poultry. Mitochondrial uncoupling protein
      1 (UCP-1) is known to uncouple respiration from ATP synthesis by short circuiting
      the inward proton flow, resulting in heat production. Its role seems quite well
      established in adaptive thermogenesis and energy metabolism. However, uncertainty
      still surrounds the physiological function of the recently discovered UCP-1
      homologues, UCP-2 and -3. Most of the functional characterization of these UCPs,
      to date, has been conducted in mammals. Recently, an avian UCP homologue, which
      was identified in chicken, hummingbird and king penguin, appears to play a key
      role in adaptative thermogenesis. Here, we review recent reports describing avian
      UCP (av-UCP) and discuss progress concerning the molecular mechanisms and
      potential role of the av-UCP in thermogenesis regulation in avian species.

PMID- 15556383
TI  - Effects of hibernation on mitochondrial regulation and metabolic capacities in
      myocardium of painted turtle (Chrysemys picta).
AB  - Painted turtles hibernating during winter may endure long-term exposure to low
      temperature and anoxia. These two conditions may affect the aerobic capacity of a
      tissue and might be of particular importance to the cardiac muscle normally
      highly reliant on aerobic energy production. The present study addressed how
      hibernation affects respiratory characteristics of mitochondria in situ and the
      metabolic pattern of turtle myocardium. Painted turtles were acclimated to
      control (25 degrees C), cold (5 degrees C) normoxic and cold anoxic conditions.
      In saponin-skinned myocardial fibres, cold acclimation increased mitochondrial
      respiratory capacity and decreased apparent ADP-affinity. Concomitant anoxia did
      not affect this. Creatine increased the apparent ADP-affinity to similar values
      in the three acclimation groups, suggesting a functional coupling of creatine
      kinase to mitochondrial respiration. As to the metabolic pattern, cold
      acclimation decreased glycolytic capacity in terms of pyruvate kinase activity
      and increased lactate dehydrogenase (LHD) activity. Concomitant anoxia
      counteracted the cold-induced decrease in pyruvate kinase activity and increased
      creatine kinase activity. In conclusion, cold acclimation seems to increase
      aerobic and decrease anaerobic energy production capacity in painted turtle
      myocardium. Importantly, anoxia does not affect the mitochondrial functional
      integrity but seems to increase the capacity for anaerobic energy production and
      energy buffering.

PMID- 15556384
TI  - Nutritional and sanitary statuses alter postweaning development of caecal
      microbial activity in the rabbit.
AB  - The postweaning development of caecal microbial activity was studied in the
      rabbit according to the sanitary status (conventional "C" vs. specified pathogen
      free "SPF") and the nutritional status (standard-fibre "SF" vs. deficient-fibre
      "DF" diet). The two diets were distributed ad libitum from weaning (28 days) to
      70 days of age, respectively, to 80 C and 72 SPF rabbits. From 28 to 42 days, the
      volatile fatty acids concentration in the caecum (tVFA) of C rabbits was 50 mM/L
      and increased by 46% between 42 and 56 days, without interactions with the diet
      effect. In parallel, the bacterial fibrolytic activity decreased for xylanase and
      CMCase (-32% and -60%, respectively, P<0.05), while pectinase activity decreased
      more regularly from 28 to 70 days (-28%, P<0.05). At weaning, tVFA was similar
      among C or SPF rabbits, while at 70 days, it decreased by 23% for SPF and
      increased in C group (+31%). Cellulasic and hemicellulasic activity of bacteria
      were two to three times lower, respectively, in SPF rabbits compared to
      conventional ones. No interaction was detected between sanitary and nutritional
      status at 70 days of age for the caecal fermentative activity. With the FD diet,
      tVFA decreased by 10%, while butyrate proportion increased by 37% (at 70 days),
      whatever the sanitary status. In 70-day-old rabbits (C or SPF group), pectinasic
      activity was reduced by 30% when rabbits were fed the FD compared to the SF one.

PMID- 15556385
TI  - Analysis of the soluble matrix of vaterite otoliths of juvenile herring (Clupea
      harengus): do crystalline otoliths have less protein?
AB  - Otoliths are calcium carbonate concretions laid down in the inner ear of fish and
      used in fish age estimation. Otoliths precipitate in the form of aragonite but
      aberrant precipitation may result in vaterite formation instead of aragonite.
      Vaterite otoliths are more translucent than aragonite. The quantity of HCl
      soluble proteins (SP) was measured in the vaterite otoliths and their aragonite
      pairs of one year old reared herring Clupea harengus to assess the changes
      induced by the precipitation of vaterite in the amount of soluble proteins in the
      otolith. Results showed that vaterite otoliths had as much soluble proteins as
      their aragonite pairs (p>0.05). Due to the lower density of the vaterite,
      vaterite otoliths were lighter than their aragonite pairs (p<0.05) which
      explained that protein concentrations were significantly higher (p<0.05) than in
      aragonite otoliths. These results indicate that the precipitation of vaterite in
      otoliths did not affect the inclusion of soluble proteins. Furthermore, they
      suggest that soluble proteins do not affect the translucent or opaque appearance
      of otoliths. Differences in translucency may instead be caused by the amounts of
      insoluble proteins or by differences in the physical properties of proteins.
      Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of the
      otolith proteins revealed two bands at 50 and 62 kDa in both aragonite and
      vaterite otoliths suggesting that the precipitation of vaterite in the otolith is
      not controlled by either of these two proteins present in the otolith.

PMID- 15556386
TI  - Regulated bradycardia in the pulmonate limpet Siphonaria (Gastropoda: Mollusca)
      during pollutant exposure: implication for biomarker studies.
AB  - Although the cardiac activity of invertebrates is now widely used as a biomarker
      of marine pollution, few studies consider the intrinsic factors causing the
      variability of heart rate (HR), including the physiological states associated
      with metabolic depression and behavioural isolation. We examined the cardiac
      responses to copper exposure of a pulmonate limpet (Siphonaria capensis Quoy and
      Gaimard), known to adaptively depress heart rate (and metabolic rate) under
      naturally stressful conditions (hyposalinity). Analysis of variance was used to
      assess the effects of copper concentration (0-1000 microg/L), exposure time (0-2
      h), and individual difference (eight limpets per concentration) on heart rate
      parameters. Minute by minute heart rate (HR) and heart rate variability (HRV),
      and bradycardia (< or =10 beats/min) were determined from continuous recording
      traces. Most of the HR variance was attributable to the interaction of
      concentration and individuals (35.8%). Considerably lower mean HRs for the higher
      range of copper concentrations (250 to 1000 microg/L), compared to the lower
      range (0 to 50 microg/L), were attributable to the virtually exclusive induction
      of bradycardia in the higher concentration treatments. With increasing
      concentration, bradycardia was induced sooner and became less interspersed with
      near normal heart rates (i.e., less episodic). This regulated bradycardial
      response is apparently associated with isolation (avoidance) behaviour rather
      than with copper uptake. These findings have implications for biomarker exercises
      which use heart rate, in cases where invertebrates depress metabolism.

PMID- 15556387
TI  - IGF-I and IGF-II mRNA expression in slow and fast growing families of USDA103
      channel catfish (Ictalurus punctatus).
AB  - The objective of this study was to examine insulin-like growth factor (IGF)-I and
      IGF-II mRNA levels in fast and slow growing families of catfish. Relative levels
      of IGF-I and IGF-II mRNA were determined by real-time PCR. Family A exhibited a
      specific growth rate (SGR) of 3.6 and was designated as fast growing, while
      family H exhibited a SGR of 3.1 and was designated as slow growing (P=0.017).
      Levels of IGF-II mRNA were 3.3-fold greater (P=0.006) in muscle for the fast
      growing family compared to the slow growing family. Levels of IGF-II mRNA were
      1.8-fold greater (P=0.049) in liver for the fast growing family compared to the
      slow growing family. Levels of IGF-II mRNA from both fast and slow families were
      12.2-fold greater (P<0.001) in muscle and 5.8-fold greater (P=0.021) in liver,
      respectively, compared to levels of IGF-I mRNA. Muscle and liver levels of IGF-I
      mRNA were similar between families. Elevated levels of IGF-II mRNA in muscle and
      liver compared to IGF-I mRNA, as well as differences in levels of IGF-II mRNA
      between fast and slow growing families of fish suggests a role of IGF-II in
      growth of channel catfish.

PMID- 15556388
TI  - Intestinal capacity of P-glycoprotein is higher in the juniper specialist,
      Neotoma stephensi, than the sympatric generalist, Neotoma albigula.
AB  - Permeability-glycoprotein (Pgp) is a membrane-bound, ATP-dependent, transport
      protein that excludes many cytotoxic compounds including plant metabolites and
      pollutants from the barrier epithelia of many tissues including the small
      intestine. We hypothesized that intestinal Pgp capacity would be higher in
      Neotoma stephensi, a specialist on Juniperus monosperma known to be high in plant
      toxins, than the sympatric generalist, Neotoma albigula, which consumes juniper
      in the field, but is unable to tolerate a high juniper diet. We measured Pgp
      activity as the difference in accumulation of a known Pgp substrate, digoxin,
      between everted sections of small intestine exposed to ethanol vehicle control
      and a maximal level of a known competitive inhibitor of Pgp, cyclosporin A. We
      estimated intestinal capacity by averaging Pgp activity along the intestine and
      multiplying by total small intestine mass. These first measures of Pgp in wild
      mammals show a significant difference among species with the juniper specialist,
      N. stephensi, exhibiting a 2.4 fold higher capacity than the generalist, N.
      albigula. This result suggests that Pgp may play a role in the ability of N.
      stephensi to tolerate juniper.

PMID- 15556389
TI  - Sources and timing of calcium mobilization during embryonic development of the
      corn snake, Pantherophis guttatus.
AB  - Embryos of oviparous Reptilia (=turtles, lepidosaurs, crocodilians and birds)
      extract calcium for growth and development from reserves in the yolk and
      eggshell. Yolk provides most of the calcium to embryos of lizards and snakes. In
      contrast, the eggshell supplies most of the calcium for embryonic development of
      turtles, crocodilians and birds. The yolk sac and chorioallantoic membrane of
      birds recover and transport calcium from the yolk and eggshell and homologous
      membranes of squamates (lizards and snakes) probably transport calcium from these
      two sources as well. We studied calcium mobilization by embryos of the snake
      Pantherophis guttatus during the interval of greatest embryonic growth and found
      that the pattern of calcium transfer was similar to other snakes. Calcium
      recovery from the yolk is relatively low until the penultimate embryonic stage.
      Calcium removal from the eggshell begins during the same embryonic stage and
      total eggshell calcium drops in each of the final 2 weeks prior to hatching. The
      eggshell supplies 28% of the calcium of hatchlings. The timing of calcium
      transport from the yolk and eggshell is coincident with the timing of growth of
      the yolk sac and chorioallantoic membrane and expression of the calcium binding
      protein, calbindin-D28K, in these tissues as reported in previous studies. In the
      context of earlier work, our findings suggest that the timing and mechanism of
      calcium transport from the yolk sac of P. guttatus is similar to birds, but that
      both the timing and mechanism of calcium transport by the chorioallantoic
      membrane differs. Based on the coincident timing of eggshell calcium loss and
      embryonic calcium accumulation, we also conclude that recovery of eggshell
      calcium in P. guttatus is regulated by the embryo.

PMID- 15556390
TI  - Modifications of serotonergic and adrenergic receptor concentrations in the brain
      of aggressive Canis familiaris.
AB  - The aim of the study was to measure beta-adrenergic (beta-AR) and serotonergic (5
      HTR) receptor concentrations in different brain areas (frontal cortex,
      hippocampus, hypothalamus and thalamus) of normal and aggressive dogs. Eight
      adult male dogs, 4.2+/-0.6 years old, showing no clinical signs but aggression,
      were used for the study. Eight healthy male dogs, 4.4+/-0.8 years old, with no
      history of neurological and/or behavioural disorders and accidental death, were
      used as controls. The whole frontal cortex, hippocampus, thalamus and
      hypothalamus were collected after euthanasia and plasma membrane fractions
      obtained by ultracentrifugation. beta-AR and 5-HTR were measured by binding
      assays using specific radioligand [(-)[3H]CGP 12177 and 5-hydroxy[3H]-tryptamine
      trifluoroacetate, respectively]. A significant decrease in beta-AR levels was
      observed in the frontal cortex (P=0.001), hippocampus (P<0.0001), and thalamus
      (P<0.0001) of aggressive dogs compared to controls. As far as 5-HTR are
      concerned, two receptor subtypes were detected. The two subtypes were classified
      as low-affinity (5-HTR LA) and high-affinity (5-HTR HA) serotonergic receptors
      for [3H]-hydroxytryptamine, on the basis of their affinity for [3H]
      hydroxytryptamine. 5-HTR LA significantly increased in the whole central nervous
      system (CNS) area of aggressive dogs (frontal cortex P=0.071; hippocampus
      P=0.0013; thalamus P<0.0001; hypothalamus P=0.0004); 5-HTR HA significantly
      increased only in the thalamus (P=0.0005) and hypothalamus (P=0.0002). Results
      suggest the possible role played by the catecholaminergic and serotonergic
      systems in canine aggressive behaviour. The understanding of the biological basis
      of canine aggression may enable the development of pharmacological treatments
      that would target specific neurotransmitter systems.

PMID- 15556391
TI  - Digestive chitinolytic activity in marine fishes of Monterey Bay, California.
AB  - Chitinolytic activities, both chitinase (EC 3.2.1.14) and minimum chitobiase
      (beta-N-acetyl-D-glucosaminidase; EC 3.2.1.30), were measured in stomach and
      intestinal tissues and their contents, from 13 fish species. Higher activities
      were found in the tissues than in the gut contents, and higher activities were
      seen in the stomachs than in the intestines. Demersal species exhibited
      chitobiase activities very close to their chitinase activities, suggesting that
      these fishes can degrade chitin completely to its soluble, absorbable monomer, N
      acetyl-glucosamine. This suggests that these species may catabolize chitin not
      just to penetrate prey exoskeletons but also to derive nutrients from the chitin
      itself. In contrast, three mesopelagic species exhibited low chitobiase but high
      chitinase activities. This chitobiase limitation correlated strongly with
      gastrointestinal tract morphology, with the myctophids having the greatest
      chitobiase limitation and the shortest alimentary tracts. The high chitinase
      activities measured in the myctophids reflect their ability to rapidly disrupt
      prey exoskeletons ingested during their nightly feeding in surface waters. Their
      chitobiase activities are greatly reduced because with rapid meal evacuation
      through a short gut there is little time for processing and limited energetic
      advantage in the complete degradation of chitin. These results suggest multiple
      roles for chitinolytic enzymes in marine fishes and that feeding habits and
      frequency may have a bearing on the evolution of their digestive enzymes systems.

PMID- 15556392
TI  - Nutritional homeostasis in carnivorous southern catfish (Silurus meridionalis):
      is there a mechanism for increased energy expenditure during carbohydrate
      overfeeding?
AB  - In previous growth experiments with carnivorous southern catfish (Silurus
      meridionalis), the non-fecal energy lose was positively related to dietary
      carbohydrate level. To test whether metabolic energy expenditure accounts for
      such energy loss, an experiment was performed with southern catfish juveniles
      (33.2-71.9 g) to study the effect of dietary carbohydrate level on fasting
      metabolic rate and specific dynamic action (SDA) at 27.5 degrees C. The fasting
      metabolic rate in this catfish was increased with dietary carbohydrate level, and
      the specific dynamic action (SDA) coefficient (energy expended on SDA as percent
      of assimilated energy) was not affected by dietary carbohydrate level. The
      results suggest that in southern catfish, carbohydrate overfeeding increases
      metabolic rate to oxidize unwanted assimilated carbohydrate. A discussion on the
      poor capacity of intermediate metabolism for adapting dietary carbohydrate in
      carnivorous fish and its possible relationship with facultative component of SDA
      was also documented in this paper.

PMID- 15556393
TI  - Seasonal changes in brain melatonin concentration in the three-spined stickleback
      (Gasterosteus aculeatus): towards an endocrine calendar.
AB  - Pineal organ and its hormone melatonin (N-acetyl-5-methoxytryptamine) is likely
      involved in timing and synchronisation of many internal processes, such as
      reproduction, with annual changes in environmental cues, i.e., photoperiod and
      water temperature. The seasonal changes in melatonin profile in stickleback
      brains related to the following reproductive phases were examined, and the link
      between melatonin concentrations and the stages of spawning cycle was analysed.
      Two wild populations of sticklebacks were exposed to annual environmental changes
      in their natural habitats. Brains, gonads, kidneys and livers were collected over
      2 years. Melatonin was measured using RIA and the indices, gonadosomatic (GSI),
      nephrosomatic (NSI) and hepatosomatic (HSI), were calculated. The role of
      melatonin, as a component of internal calendar engaged in the control of seasonal
      breeding in this species, is discussed. The extremely high melatonin levels
      observed in early spring (March) and autumn (October) seem to mark out a time
      frame for spawning in sticklebacks. The seasonal pattern of melatonin production
      and identified development stages of gonads suggests the potential inhibitory
      effect of the hormone on stickleback reproduction in shortening photoperiod and
      stimulatory effect in lengthening photoperiod.

PMID- 15556394
TI  - Respiratory and behavioral effects of ozone on a lizard and a frog.
AB  - Ozone at concentrations found in urban air pollution is known to have significant
      physiological effects on humans and other mammals. Exposure of the lizard,
      Sceloporus occidentalis, to 0.6 ppm ozone for 4 h at 25 degrees C induced 1.6
      degrees C of behavioral hypothermia immediately following exposure, but selected
      body temperature recovered to control 35.3 degrees C the next day. Lizards
      exposed at 35 degrees C to 0.6 ppm ozone for 4 h selected body temperatures 1.9
      degrees C below controls after exposure, and the behavioral hypothermic response
      persisted and increased to 3.3 degrees C the following day. Four-hour exposures
      of the frog, Pseudacris cadaverina, to 0.2 to 0.8 ppm ozone resulted in
      concentration-dependent alterations of respiration including depression of lung
      ventilation and oxygen consumption and the adoption of a low profile posture that
      reduced the exposed body surface. Ozone levels in wilderness habitats downwind of
      urban sources can potentially have stressful physiological effects on wildlife.
      Defensive physiological and behavioral reactions to ozone exposure may interfere
      with routine activities, and oxidant air pollution may be in part responsible for
      observed wildlife population declines.

PMID- 15556395
TI  - Seasonal changes in the thermoregulation of laboratory golden hamsters during
      acclimation to seminatural outdoor conditions.
AB  - Proper adjustments of the thermoregulatory mechanisms ensure survival in the
      natural environment. In the present study, we tested the hypothesis that
      laboratory golden hamsters (Mesocricetus auratus) housed under seminatural
      outdoor conditions are able to acclimatize to daily and seasonal changes in the
      environment despite their long history of breeding in captivity. The animals
      experienced natural changes in the photoperiod and ambient temperature
      characteristic for central Poland. During experiments in the thermal gradient
      system, the daily rhythms of body temperature (measured as the temperature of
      brown adipose tissue, TBAT), preferred ambient temperature (PTa) and activity
      were measured in summer, autumn and spring. We found that mean TBAT was highest
      in autumn and least in summer, reflecting seasonal changes in the capacity for
      nonshivering thermogenesis (NST). In summer, TBAT followed the robust daily
      rhythm with the amplitude of 1.1+/-0.1 degrees C. This amplitude was depressed in
      autumn (0.2+/-0.1 degrees C) and partially restored in spring (0.4+/-0.1 degrees
      C). Seasonal changes in the daily amplitude of TBAT recorded during both
      transitional periods, i.e., in autumn and spring, seem to be associated with
      hamsters' hibernation. In autumn, mean daily PTa was lower than in summer and
      spring, indicating the lowering of a set point for core body temperature (Tb)
      regulation. Locomotor activity was much higher in spring than in summer and
      autumn, and it always predominated at night. We conclude that laboratory golden
      hamsters housed under seminatural conditions express daily and seasonal changes
      in the thermoregulatory mechanisms that, despite long history of breeding in
      captivity, enable proper acclimatization to seasonally changing environment and
      ensure successful hibernation and winter survival.

PMID- 15556396
TI  - The effects of temperature and artificial rain on the metabolism of American
      kestrels (Falco sparverius).
AB  - The effect of rainfall on the metabolism of birds is poorly understood. We
      measured the metabolism as rate of oxygen consumption (VO2) of four male and four
      female American kestrels (Falco sparverius) using open-circuit respirometry. We
      measured VO2 during the spring at ambient temperatures (Ta) of 5, 10, 15, and 25
      degrees C in air without rainfall and with simulated rainfall of 2.5 (low
      rainfall) and 6.1 cm h(-1) (high rainfall). Kestrel metabolism was significantly
      higher when exposed to the two rainfall levels compared to no rainfall. However,
      kestrel metabolism was not significantly different at the two rainfall levels.
      Body temperature (Tb) was significantly lower under high rainfall compared to low
      rainfall. In addition, under both rainfall levels Tb decreased with decreasing
      Ta. Calculated thermal conductance was significantly higher in kestrels exposed
      to rain compared to no rainfall. Kestrels may use sleeking behavior at high
      rainfall levels to decrease water penetration of the plumage. Daily energy
      expenditure (DEE) of kestrels exposed to rain may increase markedly, and kestrel
      energetics may be further exacerbated by wind that often accompanies natural
      rainstorms.

PMID- 15556397
TI  - Sugar preferences, absorption efficiency and water influx in a Neotropical
      nectarivorous passerine, the Bananaquit (Coereba flaveola).
AB  - Nectarivory has evolved repeatedly in a number of unrelated bird taxa throughout
      the world and nectar feeding birds, regardless of their taxonomic affiliation,
      display convergent foraging and food processing adaptations that allow them to
      subsist on weak sugar solutions. However, phylogeny influences sugar type
      preferences of nectarivores. We investigated sugar preferences, assimilation
      efficiency and water flux in a Neotropical honeycreeper, the Bananaquit (Coereba
      flaveola; Coerebidae), a member of a radiation of tanagers and finches.
      Bananaquits showed no preference for nearly equicaloric (25% w/v) sucrose,
      glucose, fructose or glucose-fructose mixtures in pair-wise choice tests. In
      agreement with this lack of preference, they were equally efficient at absorbing
      sucrose and both hexoses. Apparent assimilation efficiency of these sugars was
      around 97.5%. In pair-wise tests, Bananaquits displayed a strong preference for
      the most concentrated sucrose solution when the lowest concentration ranged from
      276 to 522 mM. Between 522 and 1120 mM sucrose solution concentrations,
      Bananaquits were able to adjust their volumetric food intake in order to maintain
      a constant energy intake. At solution concentration of 276 mM, birds could not
      maintain their rate of energy intake by increasing food consumption enough. We
      consider that at low sugar concentrations, Bananaquits faced a physiological
      constraint; they were unable to process food at a fast enough rate to meet their
      energy needs. We also explored the possibility that dilute nectars might be
      essential to sustain high water needs of Bananaquits by allowing them to control
      osmolarity of the food. Between 276 and 1120 mM sucrose solution concentrations,
      average amount of free water drunk by Bananaquits was independent of food
      concentration. They drank very little supplementary water and did not effectively
      dilute concentrated nectars. The evidence suggests that water bulk of dilute
      nectars is a burden to Bananaquits.

PMID- 15556399
TI  - RNA interference and chemically modified small interfering RNAs.
AB  - RNA interference (RNAi) is a powerful biological process for specific silencing
      of gene expression in diversified eukaryotic cells and has tremendous potential
      for functional genomics, drug discovery through in vivo target validation, and
      development of novel gene-specific medicine. The future success of this
      technology relies on identifying appropriate chemical modifications to improve
      stability, potency and in vivo cellular delivery. The present review summarizes
      the role of the chemist's toolbox in this emerging technology.

PMID- 15556400
TI  - Nucleic acid crystallography: current progress.
AB  - Fifty years after the publication of the DNA double helix model by Watson and
      Crick, new nucleic acid structures keep emerging at an ever-increasing rate. The
      past three years have brought a flurry of new oligonucleotide structures,
      including those of a Hoogsteen-paired DNA duplex, Holliday junctions, DNA-drug
      complexes, quadruplexes, a host of RNA motifs and various nucleic acid analogues.
      Major advances were also made in terms of the structure and function of catalytic
      RNAs. These range from improved models of the phosphodiester cleavage reactions
      catalyzed by the hairpin and hepatitis delta virus ribozymes to the visualization
      of a complete active site of a group I self-splicing intron with bound 5'- and 3'
      exons. These triumphs are complemented by a refined understanding of cation
      nucleic-acid interactions and new routes to the generation of derivatives for
      phasing of DNA and RNA structures.

PMID- 15556401
TI  - Artificial metallo-DNA: a bio-inspired approach to metal array programming.
AB  - The structure of DNA is such that the multi-array of functionalized units with
      desired numbers and sequences within the DNA is possible. In particular, to
      replace DNA bases, which are biologically important elements for gene expression,
      by alternative bases would provide powerful tools for programming molecular
      arrays in a pre-designed manner. This review focuses on recent chemical
      approaches to self-assembled metal arrays within DNA with metal-mediated base
      pairing.

PMID- 15556402
TI  - Self-assembly of reactive amphiphilic block copolymers as mimetics for biological
      membranes.
AB  - Over the years, polymers have attracted a great deal of interest because they
      offer a unique platform for the development of materials in fields as diverse as
      biomedicine and packaging. Many of these purposes use polymers that had been
      developed for totally different applications. Recently, however, chemical
      tailoring and molecular and supramolecular control of the chemistry and, thus,
      the physical and biological response have become a key interest of many
      researchers. In particular, systems that operate in aqueous media have become an
      intensely researched field. This is mostly because many devices must be
      biocompatible, which implies that they have to function in aqueous solutions.
      Over the past few years, new approaches for mimicking cell surfaces, for
      generating biocompatible and bioactive drug delivery systems, and for directed
      targeting have been developed. One recent development is polymeric systems with
      an enhanced biofunctionality, such as amphiphilic block copolymers that can act
      as mimetics for biological membranes. Because there are virtually no limits to
      combinations of monomers, biological and synthetic building blocks, ligands,
      receptors, and other proteins, polymer hybrid materials show a great promise for
      applications in biomedicine and biotechnology.

PMID- 15556403
TI  - Covalent capture: a natural complement to self-assembly.
AB  - The utility of peptide self-assembly can be extended by covalent capture of these
      supramolecular materials. Disulfide bond formation, native chemical ligation,
      olefin metathesis, radical capture and oxidative lysine cross-linking have been
      used recently to help stabilize and characterize a variety of self-assembled
      peptides. These include natural peptides, proteins and protein mimics such as
      alpha-helical coiled coils, amyloid-like beta-sheet fibres, portions of p53,
      glutathione S-transferase and elastin as well as unnatural peptide constructs
      such as cyclic peptide nanotubes and cylindrical micelles of peptide amphiphiles.

PMID- 15556404
TI  - Polyubiquitin chains: polymeric protein signals.
AB  - The 76-residue protein ubiquitin exists within eukaryotic cells both as a monomer
      and in the form of isopeptide-linked polymers called polyubiquitin chains. In two
      well-described cases, structurally distinct polyubiquitin chains represent
      functionally distinct intracellular signals. Recently, additional polymeric
      structures have been detected in vivo and in vitro, and several large families of
      proteins with polyubiquitin chain-binding activity have been discovered. Although
      the molecular mechanisms governing specificity in chain synthesis and recognition
      are still incompletely understood, the scope of signaling by polyubiquitin chains
      is likely to be broader than originally envisioned.

PMID- 15556405
TI  - Cell surface biology mediated by low affinity multivalent protein-glycan
      interactions.
AB  - Glycan-binding proteins mediate diverse aspects of cell biology including
      pathogen recognition of host cells, cell trafficking, endocytosis and modulation
      of cell signaling. This is accomplished despite the intrinsic low affinity for
      their ligands through multivalent interactions that increase effective affinity
      and adhesive force. Recent successes in the rational design of high-affinity
      ligands for glycan-binding proteins offer the promise to create well-defined
      tools for exploring the structure and functions of this class of receptors.

PMID- 15556406
TI  - From life's origins to a synthetic biology.

PMID- 15556407
TI  - The importance of prebiotic chemistry in the RNA world.
AB  - In vitro selection experiments have clearly demonstrated that RNA can perform
      many of the functions necessary to support an RNA world. Moreover, it appears
      that novel functions could have readily evolved from existing functional RNA
      molecules. Therefore, diverse molecular ecosystems could potentially have arisen
      from an initial, small population of functional replicators. These findings
      suggest that the sequences of living systems may have been determined in part by
      chance occurrences at origins. Any extrapolations linking sequences (as opposed
      to functions) obtained in the laboratory to what may have occurred ca. 4 billion
      years ago are tenuous at best. Thus, perhaps the best way to understand origins
      is not by examining relatively unconstrained sequence information, but by
      examining the inherent constraints imposed by prebiotic chemistry.

PMID- 15556408
TI  - Minimal self-replicating systems.
AB  - Minimal self-replicating systems typically consist of three components: a product
      molecule, and two substrate molecules that become joined to form another product
      molecule. An important characteristic of self-replicating systems is the ability
      of the product to catalyze the formation of additional product, resulting in
      autocatalytic behavior. Recent advances in the area of self-replication have led
      to improved efficiency of autocatalysis, both by increasing the fraction of
      product molecules that can participate in further rounds of replication, and by
      improving the efficiency of the catalysts themselves. This review analyzes
      chemical self-replicating systems that have been developed to date and discusses
      ongoing challenges in this area of research.

PMID- 15556409
TI  - Peptide self-assembly as a model of proteins in the pre-genomic world.
AB  - Excellent catalytic efficiency has been obtained within a series of self
      replicating peptides, and nucleobase inclusion into a salt-switchable self
      replicating peptide is found to override the switch. Interestingly, cross
      catalytic formation of an RNA aptamer is reported with a cationic peptide, and
      novel, amide-based biopolymers have been designed to self assemble.

PMID- 15556410
TI  - Nucleic-acid-templated synthesis as a model system for ancient translation.
AB  - The translation of nucleic acids into synthetic structures with expanded
      functional potential has been the subject of considerable research, with
      applications including small-molecule and polymer evolution, reaction discovery
      and sensing. Here, we review properties of nucleic-acid-templated synthesis in
      the context of requirements for prebiotic translation. This analysis highlights
      the chemical possibilities of ancient translation systems, as well as challenges
      that these systems may have faced.

PMID- 15556411
TI  - The place of metabolism in the origin of life.
AB  - Metabolism and replication are generally considered essential features of
      biological life. Workers in the field of the origin of life are mostly split into
      two groups, depending on which of these two functions is postulated to have
      occurred first. Because of difficulties encountered by the replication-first (or
      genetics-first) approach, some workers have postulated that a highly developed
      metabolism must have originated before replication and the formation of a genetic
      apparatus. However, as supporters of a replication-first approach have pointed
      out, and as is discussed in this article, the alternative metabolism-first
      approach has fundamental problems that have not been sufficiently addressed.

PMID- 15556412
TI  - Replicating vesicles as models of primitive cell growth and division.
AB  - Primitive cells, lacking the complex bio-machinery present in modern cells, would
      have had to rely on the self-organizing properties of their components and on
      interactions with their environment to achieve basic cellular functions such as
      growth and division. Many bilayer-membrane vesicles, depending on their
      composition and environment, can exhibit complex morphological changes such as
      growth, fusion, fission, budding, internal vesicle assembly and vesicle-surface
      interactions. The rich dynamic properties of these vesicles provide interesting
      models of how primitive cellular replication might have occurred in response to
      purely physical and chemical forces.

PMID- 15556413
TI  - Amyloidogenic domains, prions and structural inheritance: rudiments of early life
      or recent acquisition?
AB  - Amyloids are self-assembled fibre-like beta-rich protein aggregates.
      Amyloidogenic prion proteins propagate amyloid state in vivo and transmit it via
      infection or in cell divisions. While amyloid aggregation may occur in the
      absence of any other proteins, in vivo propagation of the amyloid state requires
      chaperone helpers. Yeast prion proteins contain prion domains which include
      distinct aggregation and propagation elements, responsible for these functions.
      Known aggregation and propagation elements are short in length and composed of
      relatively simple sequences, indicating possible ancient origin. Prion-like self
      assembled structures could be involved in the initial steps of biological
      compartmentalization in early life.

PMID- 15556414
TI  - Is there a common chemical model for life in the universe?
AB  - A review of organic chemistry suggests that life, a chemical system capable of
      Darwinian evolution, may exist in a wide range of environments. These include non
      aqueous solvent systems at low temperatures, or even supercritical dihydrogen
      helium mixtures. The only absolute requirements may be a thermodynamic
      disequilibrium and temperatures consistent with chemical bonding. A solvent
      system, availability of elements such as carbon, hydrogen, oxygen and nitrogen,
      certain thermodynamic features of metabolic pathways, and the opportunity for
      isolation, may also define habitable environments. If we constrain life to water,
      more specific criteria can be proposed, including soluble metabolites, genetic
      materials with repeating charges, and a well defined temperature range.

PMID- 15556415
TI  - Molecular structure and dynamics of liquids: aqueous urea solutions.
AB  - In this review a multi-technical approach to the analysis of the structure and
      dynamics of the urea/water system is described. The reorientational movement of
      the solute molecule is investigated by the analysis of spectral band-shapes, as
      well as with the use of the optical Kerr effect (OKE) and molecular dynamics
      simulation (MDS). The effect of solute concentration on the structure and
      dynamics of the aqueous solutions (aggregation, orientational distribution,
      solvation...) is studied by molecular dynamics simulation and neutron scattering.
      The results obtained by other techniques are included to provide a critical
      analysis. Finally, the low-frequency Raman spectra of the system are interpreted
      on the basis of the semi-quantitative information obtained by molecular dynamics
      simulation.

PMID- 15556416
TI  - UVRR spectroscopic studies of valinomycin complex formation in different
      solvents.
AB  - We investigated the complexation of valinomycin (VM) in different solvent
      environments with the aid of the UVRR spectroscopy. By probing the 206.5 and 229
      nm excited Raman spectra, we showed that new bands are observed around 1700 and
      1290 cm(-1). We assigned the 1700 cm(-1) band to the hydrogen bonded ester
      carbonyl stretching vibration. In a polar solvent, VM-K(+) complexation shows
      significant intensity changes in amide and ester carbonyl stretching region.
      Because of the small amount of conformational interconversion, complexation has a
      negligible effect on other band intensities including, the amide III, C(alpha)H,
      and amide II. We also showed the effects of the solvent polarity on the solution
      conformation of VM.

PMID- 15556417
TI  - A near-infrared Fourier transform Raman spectroscopy of epidermal keratinocytes:
      changes in the protein-DNA structure following malignant transformation.
AB  - We report here the use of near-infrared (NIR) Fourier transform (FT) Raman
      spectroscopy to analyze normal human epidermal keratinocytes prior to and
      following malignant transformation. Our analysis indicates specific Raman
      spectral differences between immortalized (HPK1A) and malignant ras transformed
      (HPK1A-ras) cells. In addition, striking spectral differences are seen in the DNA
      isolated from these cells and particularly in the 843/810 cm(-1) ratio with
      values of 1.6 +/- 0.13 in HPK1A cells and 0.68 +/- 0.09 in HPK1A-ras cells (mean
      +/- S.D., n = 12, P < 0.001) indicating specific alterations in the backbone
      conformation markers following malignant transformation. Subsequently, we
      analysed the effect of a strong inhibitor of keratinocyte growth, the Vitamin D
      analog EB1089, on the Raman spectra of intact cells and on the 843/810 cm(-1)
      ratio in the DNA isolated from both cell lines. Specific changes were observed in
      intact cells in the 1300-750 cm(-1) region. Furthermore, the 843/810 cm(-1) ratio
      of isolated DNA from HPK1A cells was not affected by EB1089 but significantly
      increased in DNA isolated from HPK1A-ras cells so much that it became closer to
      the value observed for HPK1A cells (1.07 +/- 0.10). Our data suggest that Raman
      analysis of DNA and in particular the 843/810 cm(-1) ratio can provide useful
      indices of malignant transformation and efficacy of anticancer agents.

PMID- 15556418
TI  - HF and DFT studies of the structure and vibrational spectra of 8-hydroxyquinoline
      and its mercury(II) halide complexes.
AB  - The geometry, frequency and intensity of the vibrational bands of 8
      hydroxyquinoline (8-HOQ) were obtained by HF and density functional theory (DFT)
      with BLYP and B3LYP functionals and 6-31G(d) as the basis set. The optimized bond
      lengths and bond angles are in good agreement with the X-ray data. The
      vibrational spectra of 8-HOQ which is calculated by the HF and DFT methods,
      reproduces the vibrational wavenumbers and intensities with an accuracy, which
      allows reliable vibrational assignments. Complexes of the type Hg(8-HOQ)X(2)
      [where X = Cl , Br] have been studied in the 4000-200 cm(-1) region, and
      assignment of all the observed bands were made. The analysis of the infrared
      spectra indicates that there are some structure-spectra correlations.

PMID- 15556419
TI  - Near-infrared spectroscopic study of selected hydrated hydroxylated phosphates.
AB  - Near-infrared spectroscopy has been applied to a suite of hydrated hydroxylated
      phosphate minerals including cacoxenite, hureaulite, planerite, gormanite and
      wardite. The NIR spectra may be conveniently divided into three regions (a) the
      first hydroxyl fundamental, (b) the water HOH overtone and (c) the region between
      4000 and 4800 cm(-1) where combination bands resulting from the bands in the mid
      IR. For each of these regions, the minerals show distinctive spectra which enable
      their identification and characterisation. NIR spectroscopy is a less used
      technique which does have great application for the study of minerals,
      particularly minerals which have hydrogen in the structure either as hydroxyl
      units or as water bonded to the cation or as zeolitic water as is the case for
      cacoxenite. The study of minerals on planets is topical and NIR spectroscopy
      provides a rapid technique for the distinction and identification of minerals.

PMID- 15556420
TI  - Near-infrared spectroscopy of stitchtite, iowaite, desautelsite and arsenate
      exchanged takovite and hydrotalcite.
AB  - The hydrotalcite minerals stitchtite, iowaite and desautelsite together with the
      arsenate exchanged takovite and arsenate exchanged hydrotalcite have been studied
      using near-IR reflectance spectroscopy. Each mineral has its own characteristic
      NIR spectrum enabling recognition of the particular hydrotalcite. As such the
      technique has application in the field for the analysis and identification of
      hydrotalcites. Hydrotalcites have proven useful as an anion exchange material.
      Takovite and hydrotalcite were used to exchange carbonate anions by arsenate.
      Three Near-IR spectral regions are identified: (a) the high wavenumber region
      between 6400 and 7400 cm(-1) attributed to the first overtone of the fundamental
      hydroxyl stretching mode, (b) the 4800-5400 cm(-1) region attributed to water
      combination modes of the hydroxyl fundamentals of water, and (c) the 4000-4800
      cm(-1) region attributed to the combination of the stretching and deformation
      modes of the MOH units of the hydrotalcites. NIR spectroscopy enables the
      separation of the hydroxyl bands of the water and M-OH units for the
      hydrotalcites. Compared with the NIR spectroscopy of the structural units of the
      hydrotalcites namely gibbsite and brucite, the bands are broad.

PMID- 15556421
TI  - Diode laser spectroscopy of the fundamental bands of 12C14N, 13C14N, 12C15N,
      13C15N free radicals in the ground 2 Sigma+ electronic state.
AB  - Rotationally resolved spectra of the fundamental band of the CN free radical in
      four isotopic forms have been measured using tunable diode laser absorption
      spectroscopy. The source of the radical was a microwave discharge in a mixture of
      isotopically selected methane and nitrogen diluted with argon. The lines were
      measured to an accuracy of 5 x 10(-4) cm(-1) and fitted to the formula for the
      vibration rotation spectrum of a diatomic molecule, including quartic distortion
      constants. The band origins of each of the isotopomers from the five parameter
      fits were found to be 12C14N: 2042.42115(38) cm(-1), 13C14N: 2000.08479(23) cm(
      1), 12C15N: 2011.25594(25) cm(-1), 13C15N: 1968.22093(33) cm(-1) with one
      standard deviation from the fit given in parenthesis. Some of the lines showed a
      resolved splitting due to the spin rotation interaction. This was averaged for
      fitting purposes. The average equilibrium internuclear distance derived from the
      upsilon = 0 and 1 rotational constants of the four isotopomers is 1.171800(6) A
      which is in good agreement with the value determined from microwave spectroscopy.

PMID- 15556422
TI  - An effective fluorescent chemosensor for the detection of copper(II).
AB  - The fluorescent compound N-substituted 2,6-bis(benzimidazol-2-yl)pyidine (1) has
      been synthesized. The fluorescent characteristics of the compound 1 and 2,6
      bis(benzimidazol-2-yl)pyidine (2) and the complexes formed between the two
      compounds and different metal ions have also been investigated. The results show
      that the compound 1 possesses a specific ability to form complex with Cu(2+) ion,
      but the compound 2 have not such a property. It is proposed that the specific
      recognition ability of compound 1 to Cu(2+) may be attributed to the cyclic
      configuration of this compound in polar solvent.

PMID- 15556423
TI  - The IR reflectance spectra of the nu 3(SO4(2-)) and nu 4(SO4(2-)) band regions of
      some Tutton salts using polarized radiation: testing the model dielectric
      function.
AB  - The investigation of the vibrational bands of the SO(4)(2-) ions (in the nu(3)
      and nu(4) frequency regions) of six different Tutton salts was performed with
      specular IR reflectance spectroscopy using polarized radiation, on single crystal
      samples. The reflectance function under oblique incidence using dielectric model
      function as parameter (originally derived for optically uniaxial crystals)
      appeared to be readily applicable for the investigated monoclinic crystals. The
      frequencies of the transversal and longitudinal phonons were obtained by fitting
      of spectra recorded from (0 1 0), (0 0 1) and (1 0 0) crystal planes. Further,
      the symmetry types of all experimentally detected phonons were identified. Some
      of the results were further confirmed from IR absorption spectra recorded at
      liquid nitrogen temperature (LNT) of isomorphously isolated SO(4)(2-) ions into
      the corresponding selenate matrices.

PMID- 15556424
TI  - New organotin(IV) ascorbates: synthesis, spectral characterization, biological
      and potentiometric studies.
AB  - New organotin(IV) ascorbates of the general formulae R(3)Sn(HAsc) (where R = Me ,
      n-Pr, n-Bu and Ph) and R(2)Sn(Asc) (where R = n-Bu and Ph) have been synthesized
      by the reaction of R(n)SnCl(4-n) (where n = 2 or 3) with monosodium-l-ascorbate.
      The bonding and coordination behaviour in these complexes are discussed on the
      basis of UV-Vis, IR, Far-IR, (1)H and (13)C NMR, and (119)Sn Mossbauer
      spectroscopic studies. L-Ascorbic acid acts as a monoanionic bidentate ligand in
      R(3)Sn(HAsc) coordinating through O(1) and O(3). The Mossbauer studies together
      with IR and NMR studies suggest that for these polymeric derivatives, the
      polyhedron is trigonal bipyramidal around tin with three organic groups in the
      equatorial positions. In R(2)Sn(Asc), L-ascorbic acid acts as dianionic
      tetradentate ligand and a polymeric structure with octahedral geometry around tin
      with trans organic groups has been tentatively proposed. The complexes have been
      assayed for their anti-inflammatory and cardiovascular activity. Ph(2)Sn(Asc) has
      been found to show the highest activity among the studied complexes. It is
      suggested on the basis of potentiometric studies of Me(2)Sn(IV) and Me(3)Sn(IV)
      systems with L-ascorbic acid that under physiological conditions (pH = 7.0)
      Me(2)Sn(HAsc)(OH) (approximately 60%), Me(2)Sn(OH)(2) (approximately 40%) and
      Me(3)Sn(HAsc) (approximately 60%), Me(3)Sn(OH) (approximately 40%), respectively,
      are existing, which may be responsible for their biological activities.

PMID- 15556425
TI  - The application of NIR Raman spectroscopy in the assessment of serum thyroid
      stimulating hormone in rats.
AB  - Serum blood samples of euthyroid and thyroidectomized rats treated with
      thyrotropin-releasing hormone (TRH) were analyzed on aluminum substrates using
      the near-infrared Raman spectroscopy (830 nm). Spectra of thyroid-stimulating
      hormone (TSH), TRH and prolactin standards were obtained. Differences between
      Raman spectra profiles of control and Tx + TRH samples groups were found. These
      differences were confirmed by the linear discriminant analysis (LDA), which
      presents a good classification between groups. It is supposed that these
      differences are produced by the increment of TSH in the thyroidectomized rats.

PMID- 15556426
TI  - Determination of the overlapping pKa values of resorcinol using UV-visible
      spectroscopy and DFT methods.
AB  - In this paper we determine the overlapping pK(a) values of resorcinol in water,
      applying a UV-Vis spectroscopic method that uses absorbance diagrams. On the
      other hand, in order to explain the pK(a) values obtained, we also investigate
      the molecular conformations and solute-solvent interactions of the resorcinate
      anions, using ab initio and density functional theory methods. Several ionization
      reactions and equilibria in protic solvents, which possess a high hydrogen-bond
      donor capability, are proposed. The mentioned reactions and equilibria
      constituted the indispensable theoretical basis to calculate the acidity
      constants of resorcinol. Basis sets at the HF/6-31 + G(d) and B3LYP/6-31 + G(d)
      levels of theory were used for calculations. Tomasi's method was used to analyze
      the formation of intermolecular hydrogen bonds between the resorcinate anions and
      water molecules. In this way, it was determined that in alkaline aqueous
      solutions the monoanion and dianion of resorcinol are solvated with two and four
      molecules of water, respectively. The agreement between the experimentally
      determined pK(a) values and those reported in the literature demonstrates the
      applicability and accurateness of the spectroscopic method here used. On the
      other hand, the agreement between the experimental and theoretically calculated
      pK(a) values provides solid support for the acid-base reactions proposed in this
      work.

PMID- 15556427
TI  - Time-resolved fluorescence spectroscopic and scanning near-field optical
      microscopic studies of rhodamine dye adsorbed in cationic Langmuir-Blodgett
      films.
AB  - The fluorescence lifetimes decays and picosecond time-resolved fluorescence
      spectra were measured to investigate the dynamics of the excited state of
      sulforhodamine B (SRB) molecules adsorbed in the mono- and multilayered Langmuir
      Blodgett (LB) films of octadecylamine. Steady-state and time-resolved
      fluorescence spectroscopy reveals that the fluorescence lifetimes and contents of
      the monomer and dimers in the molecular organizates depend upon the concentration
      of the dye in the solution and the adsorption process. SRB dye molecules adsorbed
      in LB films have been imaged with scanning near-field optical microscopy (SNOM).
      This information is exploited to map the distribution with molecular spatial
      resolution. SNOM provide the visual evidence of the monomers and dimers of SRB in
      cationic LB films.

PMID- 15556428
TI  - New luminescent terbium complex for the determination of DNA.
AB  - New terbium complexes of derivatives of 2-oxo-4-hydroxy-quinoline-3-carboxylic
      acid are reported, which are highly luminescent, water soluble and do not require
      luminescence enhancers. The triplet-state energy levels of the ligands, the
      relative quantum yields (QYs) and the excitation maxima of the respective terbium
      chelates were determined. The large luminescence enhancement of one of these
      complexes by nucleic acids was investigated and a mechanism of its interaction
      with DNA is proposed. The optimal conditions for determination of DNA are equal
      concentrations of Tb(3+) and ligand R(1) (C = 1 x 10(-6) M), pH 9.0. Under
      optimal conditions the luminescence intensity (RI) is proportional to the
      concentration of fish sperm DNA (fsDNA) or calf thymus DNA (ctDNA), respectively,
      within the range of 0.05-1.5 microg ml(-1). The detection limits were 10 ng ml(
      1) for fsDNA and 12 ng ml(-1) for ctDNA.

PMID- 15556429
TI  - Vibrational spectral investigation on xanthine and its derivatives--theophylline,
      caffeine and theobromine.
AB  - A normal coordinate analysis has been carried out on four compounds having a
      similar ring structure with different side chain substitutions, which are
      xanthine, caffeine, theophylline, and theobromine. Xanthine is chemically known
      as 2,6-dihydroxy purine. Caffeine, theophylline and theobromine are methylated
      xanthines. Considering the methyl groups as point mass, the number of normal
      modes of vibrations can be distributed as Gamma(vib) = 27 A' + 12 A" based on
      C(s) point group symmetry associated with the structures. In the present work 15
      A' and 12 A'' normal modes are considered. A new set of orthonormal symmetry co
      ordinates have been constructed. Wilson's F-G matrix method has been adopted for
      the normal coordinate analysis. A satisfactory vibrational band assignment has
      been made by employing the FTIR and FT Raman spectra of the compounds. The
      potential energy distribution is calculated with the arrived values of the force
      constants and hence the agreement of the frequency assignment has been checked.

PMID- 15556430
TI  - Direct fluorimetric determination of gamma-globulin in human serum with organic
      nanoparticle biosensor.
AB  - This paper describes the development of organic fluorescence nanoparticles. The
      nanoparticles have a narrow, tunable, symmetric emission spectrum and a broad,
      continuous excitation spectrum. The nanoparticles have high room-temperature
      fluorescence quantum yields and long fluorescence lifetime. They are also
      photochemically stable and water-soluble. They were used as fluorescence
      biosensor in the determination of proteins, which was proved to be a simple,
      rapid and specific method. In comparison with single organic fluorephores, these
      nanoparticles are brighter, more stable against photobleaching, and do not suffer
      from blinking. Under optimal conditions, the linear ranges of the calibration
      curves were 0.1-4.5 microg ml(-1) for human serum albumin (HSA), 0.2-3.5 microg
      ml(-1) for bovine serum albumin (BSA) and 0.04-0.8 microg ml(-1) for gamma
      globulin (gamma-IgG), respectively. The detection limits were 0.062 microg ml(-1)
      for HSA, 0.036 microg ml(-1) for BSA and 0.022 microg ml(-1) for gamma-IgG,
      respectively. However, when the content of HSA is lower than 0.8 microg ml(-1),
      HSA makes little contribution to the fluorescence quenching. So, the method was
      applied to direct selective quantification of gamma-IgG in human blood serum
      without separation of HSA. The results were in good agreement with these reported
      by the hospital, indicating that the method presented here is not only sensitive,
      selective and simple, but also reliable and suitable for practical applications.

PMID- 15556431
TI  - Preparation and study on the inclusion complexes of two tanshinone compounds with
      beta-cyclodextrin.
AB  - Solid inclusion complexes of two tanshinones (Tans): tanshinone IIA (Tan IIA),
      tanshinone I (Tan I) with beta-cyclodextrin (beta-CD) were synthesized by
      coprecipitation method. The solid inclusion complexes were characterized by using
      several analytical techniques: (1)H NMR spectra, IR spectra and thermal analysis.
      Stoichiometry of the inclusion complexes of Tans with beta-CD or HP-beta-CD is
      1:1 which was investigated in solution. The formation constants of the complexes
      were determined by UV spectrophotometry. For same kind of CD, the stability was
      in the order: Tan IIA > Tan I; for same guest, the stability was in the order: HP
      beta-CD > beta-CD. The effect of temperature on the inclusion interaction was
      examined and the thermodynamic parameters of inclusion process, Delta G, Delta H,
      Delta S were determined as well. The experimental results indicate that the
      inclusion process was an exothermic and enthalpy-driven process accompanied with
      a negative entropic contribution. The inclusion interaction between CD and Tans
      satisfied the law of enthalpy-entropy compensation.

PMID- 15556432
TI  - Copper(II) complexes of new biomimetic polydentate amide ligands: a spectroscopic
      study.
AB  - Complexes of Cu(II) with N,N'-bis(3-carboxy-1-oxopropanyl)-1,2
      ethylenediamine(C(10)H(16)N(2)O(6),L(1)), N,N'-bis(3-carboxy-1-oxopropanyl)-1,2
      phenylenediamine(C(14)H(16)N(2)O(6),L(2)), N,N'-bis(2-carboxy-1-oxophenelenyl)
      1,2-phenylenediamine(C(22)H(16)N(2)O(6),L(3)) and N,N'-bis(3-carboxy-1-oxoprop-2
      enyl)-1,2-phenylenediamine(C(14)H(12)N(2)O(6),L(4)) have been prepared and
      characterised by elemental analyses, vibrational spectra, magnetic susceptibility
      measurements, ligand field spectra, EPR spectra, thermal studies and X-ray
      diffraction spectra. Vibrational spectra indicate coordination of amide and
      carboxylate oxygens of the ligands giving a MO(4) square planar chromophore.
      Ligand field and EPR spectra support square planar geometry around Cu(II).
      [Cu(L(1))] complex has the maximum activation energy and [Cu(L(3))] complex has
      the minimum activation energy.

PMID- 15556433
TI  - Resolution enhancement of composite spectra using wavelet-based derivative
      spectrometry.
AB  - An approach based on the using of the continuous wavelet transform (CWT) in
      derivative spectrometry (DS) is considered. Within the framework of the approach
      we develop a numerical differentiation algorithm with continuous wavelets for
      improving resolution of composite spectra. The wavelet-based derivative
      spectrometry (WDS) method results in best contrast in differential curves
      compared to the conventional derivative spectrometry method. A main advantage is
      that, as opposed to DS, WDS gives stable estimations of derivative in the wavelet
      domain without using the regularization. A wavelet shape and the information
      redundancy are of the greatest importance when the continuous wavelet transform
      is used. As an appropriate wavelet we offer to utilize the nth derivative of a
      component with a priori known shape. The energy distribution into scales allows
      one to determine a unique wavelet projection and in that way to avoid the
      information redundancy. A comparative study of WDS and DS with the statistical
      regularization method (SRM) is made; in particular, limits of applicability of
      these are given. Examples of the application of both DS and WDS for improving
      resolution of synthetic composite bands and real-world composite ones coming from
      molecular spectroscopy are given.

PMID- 15556434
TI  - Spectroscopic and electrochemical studies of ruthenium and osmium complexes of
      salicylideneimine-2-thiophenol Schiff base.
AB  - The reactions between [M(3)(CO)(12)], M = Ru and Os, and salicylideneimine-2
      thiophenol Schiff base in THF under reflux gave [Ru(CO)(4)(satpH)] and
      [Os(CO)(3)(satpH(2))] complexes. Structures of the two complexes were proposed on
      the basis of spectroscopic studies. Magnetic study of [Ru(CO)(4)(satpH)]
      suggested that a change in oxidation state of the ruthenium atom from zero to +1
      was achieved via oxidative addition of the SH group with a proton displacement to
      give a low-spin d(7) electronic configuration. UV-Vis spectra of the two
      complexes in different solvents exhibited visible bands due to metal-to-ligand
      charge transfer. Electrochemical investigation of the free ligand and complexes
      showed some cathodic and anodic irreversible peaks due to interconversions
      through electron transfer.

PMID- 15556435
TI  - Autofluorescence characterization of advanced glycation end products of
      hemoglobin.
AB  - This article describes the analysis of autofluorescence of advanced glycation end
      products of hemoglobin (Hb-AGE). Formed as a result of slow, spontaneous and non
      enzymatic glycation reactions, Hb-AGE possesses a characteristic autofluorescence
      at 308/345 nm (lambda(ex)/lambda(em)). Even in the presence of heme as a
      quenching molecule, the surface presence of the glycated adduct gave rise to
      autofluorescence with the quantum yield of 0.19. The specificity of monoclonal
      antibody developed against common AGE structure with Hb-AGE was demonstrated
      using reduction in fluorescence polarization value due to increased molecular
      volume while binding. The formation of fluorescent adduct in hemoglobin in the
      advanced stage of glycation and the non-fluorescent HbA(1c) will be of major use
      in distinguishing and to know the past status of diabetes mellitus. While
      autofluorescence correlated highly with HbA(1c) value under in vivo condition (r
      = 0.85), it was moderate in the clinical samples (r = 0.55). The results suggest
      a non-linear relation between glycemia and glycation, indicating the application
      of Hb-AGE as a measure of susceptibility to glycation rather than glycation
      itself.

PMID- 15556436
TI  - Structural assignment of Diels-Alder adducts: an experimental and theoretical
      approach.
AB  - A detailed NMR analysis with total assignment of (1)H and (13)C NMR data for the
      endo and the exo adducts, obtained by Diels-Alder reaction between 2
      cyclohexenone and cyclopentadiene, is described. The unequivocal assignment of
      the endo and exo structures was performed by (1)H and (13)C NMR. These
      assignments were supported by theoretical chemical shift calculations at GIAO/HF
      level using 6-311 + g(2d, p) from optimized structures at the B3LYP/6-31g(d)
      level.

PMID- 15556437
TI  - Peisleyite an unusual mixed anion mineral--a vibrational spectroscopic study.
AB  - The mineral peisleyite has been studied using a combination of electron
      microscopy and vibrational spectroscopy. Scanning electron microscope (SEM)
      photomicrographs reveal that the peisleyite morphology consists of an array of
      small needle-like crystals of around 1 microm in length with a thickness of less
      than 0.1 microm. Raman spectroscopy in the hydroxyl stretching region shows an
      intense band at 3506 cm(-1) assigned to the symmetric stretching mode of the OH
      units. Four bands are observed at 3564, 3404, 3250 and 3135 cm(-1) in the
      infrared spectrum. These wavenumbers enable an estimation of the hydrogen bond
      distances 3.052(5), 2.801(0), 2.705(6) and 2.683(6)A. Two intense Raman bands are
      observed at 1023 and 989 cm(-1) and are assigned to the SO(4) and PO(4) symmetric
      stretching modes. Other bands are observed at 1356, 1252, 1235, 1152, 1128, 1098
      and 1067 cm(-1). The bands at 1067 cm(-1) is attributed to AlOH deformation
      vibrations. Bands in the low wavenumber region are assigned to the nu(4) and
      nu(2) out of plane bending modes of the SO(4) and PO(4) units. Raman spectroscopy
      is a useful tool in determining the vibrational spectroscopy of mixed hydrated
      multianion minerals such as peisleyite. Information on such a mineral would be
      difficult to obtain by other means.

PMID- 15556438
TI  - Effect of ligand radicals on vibrational IR, Raman and vibronic spectra of
      europium beta-diketonates.
AB  - Vibrational IR, Raman spectra and vibronic sidebands of Eu(3+) electronic
      transitions of europium tris-beta-diketonates Eu(beta)(3).Ph (beta
      dipyvaloylmethane (DPM), acetylacetone (AA), benzoylacetone (BA),
      thenoyltrifluoroacetone (TTFA) and other beta-diketones; Ph-methyl-, phenyl-, and
      nitro-derivatives of 1,10-phenanthroline (Phen)) as well as Eu(beta)(3).Bpy and
      Eu(beta)(3).D-Bpy (Bpy- and D-Bpy-H- and D-2,2'-bipyridine) were studied. Effect
      of ligand radical properties on spectra and manifestation of the reciprocal
      influence of non-equivalent ligands in spectra are discussed. Dependence of the
      spectra on electronic density distribution in both ligands as well as on the
      strength of M-O and M-N bonds at the variation of radicals of one of the ligands,
      beta or Ph, was examined. Shape of vibronic sidebands was analysed. Behaviour of
      bands in the middle and far regions of IR spectra of the series Eu(beta)(3).Phen
      and Eu(TTFA)(3).Ph was investigated. Increase of the polarising influence of
      Eu(3+) ions on Phen and Bpy molecules and strengthening the Eu-N bonds in TTFA
      compounds in comparison with DPM compounds were disclosed from the Raman spectra
      of Eu(beta)(3).Phen and Eu(beta)(3).Bpy, that is in accordance with properties of
      beta-diketone radicals. Conclusion about weaker Eu-N bonds in europium beta
      diketonates with heterocyclic diimines in comparison with corresponding nitrates
      was derived from the spectra. Spectral data concerning the relative strength of
      Eu-ligand bonds are in agreement with available X-ray data.

PMID- 15556439
TI  - Infrared and polarized Raman spectra of a noncentrosymmetric compound "sodium
      samarium fluorosilicate" NaSmSiO4.0.25NaF.
AB  - Chemical preparation, infrared and Raman spectra of sodium samarium
      fluorosilicate, NaSmSiO(4).0.25NaF are presented. The spectra are analyzed with
      regard to the symmetry, and the numbers of the SiO(4)(4-) internal vibrational
      modes observed in the Raman and infrared spectra are consistent with the
      predictions.

PMID- 15556440
TI  - Density functional study and the vibrational spectra of 4-chloro-5-fluoro-1,2
      phenylenediamine.
AB  - The solid phase FTIR and FT-Raman spectra of 4-chloro-5-fluoro-1,2
      phenylenediamine (C(6)H(6)ClFN(2)) have been recorded in the region 4000-400 and
      3500-100 cm(-1), respectively. The spectra were interpreted with the aid of
      normal coordinate analysis following a full structure optimization and force
      field calculations based on the density functional theory (DFT) using the
      standard B3LYP/6-31G( *) method and basis set combination. A close agreement was
      achieved between the observed and calculated frequencies by refinement of the
      scale factors.

PMID- 15556441
TI  - Charge-transfer interaction of iodine with some polyamidoamines.
AB  - The interaction of iodine as a sigma-acceptor with two derivatives of
      polyamidoamine dendrimers (donor), 1,8-naphthalimide polyamidoamine (PAM1) and 4
      piperidino-1,8-naphthalimide polyamidoamine (PAM2) have been investigated
      spectrophotometrically at room temperature in chloroform. The results indicate
      the formation of two CT-complexes [(PAM1)I](+)I(3)(-) and [(PAM2)(2)I](+)I(3)(-)
      with molar ratios of 1:2 and 1:1, respectively. The formation of these two
      complexes are in good agreement with their elemental analysis, infrared
      measurements and photometric titration plots based on the characteristic
      absorption bands of I(3)(-) ion around 280 and 360 nm. Moreover the formation of
      triiodide ion, I(3)(-), in both of the two complexes was supported by measuring
      their spectra in the far-infrared region. Three characteristic bands are observed
      at 125, 110 and 75 cm(-1) due to nu(as)(I-I), nu(s)(I-I) and delta(I(3)(-)),
      respectively, with C(2v) symmetry.

PMID- 15556442
TI  - Electronic absorption spectra of symmetric cationic dye in constant electric
      field.
AB  - The electronic absorption coefficient of polymer films doped with symmetric
      cationic polymethine dye external electric field constant changes is researched.
      This effect is characterised by the short-wavelength band edge intensity
      increases and it decreases on the long-wavelength edge. The dye cation charge
      distribution in the model electric field 10(8)Vm(-1) of point charges was
      calculated by the method AM1. On the basis of the quantum chemical calculations
      the spectral regularities in electric field is interpreted by the cation
      electronic charge changes. The theoretical model, based on the eigenfrequencies
      value changes of the charged anharmonic oscillators under operation field is
      offered for the observed effects description. The experimental spectra well
      correlate with the theoretically calculated.

PMID- 15556443
TI  - Spectral and magnetic studies on manganese(II), cobalt(II) and nickel(II)
      complexes with Schiff bases.
AB  - Mn(II), Co(II) and Ni(II) complexes of 2-methylcyclohexanone
      thiosemicarbazone(MCHTSC L(1)) and 2-methylcyclohexanone-(4)N-methyl-3
      thiosemicarbazone (MCHMTSC L(2)), general composition [M(L)(2)X(2)] (where M =
      Mn(II), Co(II), Ni(II), L = L(1) or L(2) and X = Cl(-), NO(3)(-), and
      [(1/2)SO(4)(2-)) have been synthesized and characterized by elemental analysis,
      magnetic susceptibility measurements, UV-vis, IR, EPR, and mass spectral studies.
      Various physico-chemical techniques suggest an octahedral geometry for all the
      complexes.

PMID- 15556444
TI  - Synthesis, spectroscopy, and electrochemistry of copper(II) complexes with N,N'
      bis(3,5-di-t-butylsalicylideneimine)polymethylenediamine ligands.
AB  - Bulky salen CuL(x) derived from aliphatic polymethylene diamines, H(2)N
      (CH(2))(x)-NH(2), where n = 2-6, and 3,5-di-t-butylsalicylaldehyde (H(2)L(x)) and
      some corresponding tetrahydrosalan complexes (CuL(x)') have been synthesized and
      characterized by their IR, UV-vis absorption and EPR spectra, by magnetic moments
      and by cyclic voltammetry in acetonitrile (for H(2)L(x)) and DMF (for CuL(x)).
      Complexes CuL(x) and CuL(x)' are magnetically normal (mu(exp) = 1.83-1.91 mu(B)).
      EPR spectra CuL(x) characterized by the axial g and A(Cu) tensors with g parallel
      > g perpendicular and without (14)N-shf resolution in CHCl(3)/toluene at 300 and
      150K. The CV studies on acetonitrile solutions of H(2)L(x) revealed a well
      defined quasi-reversible redox wave at E(1/2) = 0.95-1.15 V versus Ag/AgCl but CV
      of the CuL(x) complexes in DMF exhibit weak pronounced irreversible oxidation
      waves at E(pa)(1) = 0.51 - 098 V and E(pa)(2) = 1.16 - 1.33 V attributable to
      metal centered Cu(II/III) and ligand centered CuL(x)/CuL(x)*+ couples,
      respectively. A poorly defined wave was observed for the quasi-reversible
      reduction Cu(II)/Cu(I) at potentials less than -1.0 V.

PMID- 15556445
TI  - Analysis of ochres from Clearwell Caves: the role of particle size in determining
      colour.
AB  - Three ochre samples (A (orange-red in colour), B (red) and C (purple)) from
      Clearwell Caves, (Gloucestershire, UK) have been examined using an integrated
      analytical methodology based on the techniques of IR and diffuse reflectance UV
      visible-NIR spectroscopy, X-ray diffraction, elemental analysis by ICP-AES and
      particle size analysis. It is shown that the chromophore in each case is
      haematite. The differences in colour may be accounted for by (i) different
      mineralogical and chemical composition in the case of the orange ochre, where
      higher levels of dolomite and copper are seen and (ii) an unusual particle size
      distribution in the case of the purple ochre. When the purple ochre was ground to
      give the same particle size distribution as the red ochre then the colours of the
      two samples became indistinguishable. An analysis has now been completed of a
      range of ochre samples with colours from yellow to purple from the important site
      of Clearwell Caves.

PMID- 15556446
TI  - Spectroscopic, thermal and electrochemical studies on some nickel(II)
      thiosemicarbazone complexes.
AB  - Several complexes of thiosemicarbazone derivatives with Ni(II) have been
      prepared. Structural investigation of the ligands and their complexes has been
      made based on elemental analysis, magnetic moment, spectral (UV-Vis, i.r., (1)H
      NMR, ms), and thermal studies. The i.r. spectra suggest the bidentate
      mononegative and tridentate (neutral, mono-, and binegative) behavior of the
      ligands. Different stereochemistries were suggested for the isolated complexes.
      The thermogravimetry (TG) and derivative thermogravimetry (DTG) have been used to
      study the thermal decomposition and kinetic parameters of some ligands and
      complexes using the Coats-Redfern and Horowitz-Metzger equations. The redox
      properties and stability of the complexes toward oxidation waves explored by
      cyclic voltammetry are related to the electron withdrawing or releasing ability
      of the substituent of thiosemicarbazone moiety. The samples displayed
      Ni(II)/Ni(I) couples irreversible waves associated with Ni(III)/Ni(II) process.

PMID- 15556447
TI  - Density functional theory calculations and vibrational spectra of 3,5
      dibromopyridine and 3,5-dichloro-2,4,6-trifluoropyridine.
AB  - The solid phase mid FTIR and FT-Raman spectra of 3,5-dibromopyridine (3,5-DBP)
      and 3,5-dichloro-2,4,6-trifluoropyridine (3,5-DCTFP) have been recorded in the
      regions 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The spectra were
      interpreted with the help of normal coordinate analysis (NCA) following full
      structure optimisation and force field calculations based on the density
      functional theory (DFT) using the standard B3LYP/6-31G( *) method and basis set
      combination. The results of the calculations are applied to stimulate infrared
      and Raman spectra of the title compounds which showed excellent agreement with
      the observed spectra.

PMID- 15556448
TI  - Hydrogen bonding and molecular vibrations of 3,5-diamino-1,2,4-triazole.
AB  - This work deals with the analysis of hydrogen bonding and the vibrational
      spectroscopy of 3,5-diamino-1,2,4-triazole by means of quantum chemical
      calculations. The mid and far FTIR and FT-Raman spectra were measured in the
      condensed state. The fundamental vibrational frequencies were calculated under
      different possible symmetries by applying the density functional theory with the
      B3LYP functional and the 6-31G* basis set. The results of the calculations
      obtained under C(2) symmetry produces the global minimum on the potential energy
      surface. The vibrational spectra were interpreted with the aid of normal
      coordinate analysis based on scaled density functional force field. The infrared
      and Raman spectra were also predicted from the calculated intensities.

PMID- 15556449
TI  - EPR, mass, IR, electronic, and magnetic studies on copper(II) complexes of
      semicarbazones and thiosemicarbazones.
AB  - Copper(II) complexes having the general composition Cu(L)(2)X(2) [where L =
      isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone
      thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC), and 4
      aminoacetophenone thiosemicarbazone (LLD) and X = Cl(-), 1/2SO(4)(2-)] have been
      synthesized. All the Cu(II) complexes reported here have been characterized by
      elemental analyses, molar conductance, magnetic moment susceptibility, EI mass,
      (1)H NMR, IR, EPR, and electronic spectral studies. All the complexes were found
      to have magnetic moments corresponding to one unpaired electrons. The possible
      geometries of the complexes were assigned on the basis of EPR, electronic, and
      infrared spectral studies.

PMID- 15556450
TI  - Photoelectron spectroscopy of natural products: terpenes.
AB  - HeI photoelectron spectra of three terpenes: alpha-pinene, pulegone and cembrene
      have been measured. The analysis of their electronic structure is based on the
      comparison of measured spectra with those of related compounds and on the
      comparison with molecular structures of studied compounds. We discuss changes in
      ionization energies of C-C double bonds which are situated at different positions
      along the rings.

PMID- 15556451
TI  - Spectrofluorimetric study of the charge-transfer complexation of certain
      fluoroquinolones with 7,7,8,8-tetracyanoquinodimethane.
AB  - Simple, rapid and sensitive spectrofluorimetric methods are described, for the
      first time, for the determination of ciprofloxacin (CIP), norfloxacin (NOR),
      pefloxacin (PEF) and fleroxacin (FLE). The methods are based on the charge
      transfer (CT) reaction of these drugs as n-electron donors with 7,7,8,8
      tetracyanoquinodimethane (TCNQ) as pi-electron acceptor. TCNQ was found to react
      with these drugs to produce intensely transfer reaction complexes and the
      fluorescence intensity of the complexes was enhanced in 21-35 fold higher than
      that of the studied fluoroquinolones itself. The formation of such complexes was
      also confirmed by both infrared and ultraviolet-visible measurements. The
      different experimental parameters that affect the fluorescence intensity were
      carefully studied. At the optimum reaction conditions, the drug-TCNQ complexes
      showed excitation maxima ranging from 277 to 284 nm and emission maxima ranging
      from 451 to 458 nm. Rectilinear calibration graphs were obtained in the
      concentration range of 0.03-0.9, 0.04-1.2, 0.04-1.3 and 0.08-2.4 microg ml(-1)
      for CIP, NOR, PEF and FLE, respectively. The developed methods were applied
      successfully for the determination of the studied drugs in their pharmaceutical
      dosage forms with a good precision and accuracy compared to official and reported
      methods as revealed by t- and F-tests.

PMID- 15556452
TI  - Novel copper(II)-dien-imidazole/imidazolate-bridged copper(II) complexes. Crystal
      structure of [Cu(dien)(Him)](ClO4)2 and of [(dien)Cu(mu-im)Cu(dien)](ClO4)3, a
      homobinuclear model for the copper(II) site of the CuZn-superoxide dismutase.
AB  - The imidazolate-bridged binuclear copper(II)-copper(II) complex [(dien)Cu(mu
      im)Cu(dien)](ClO(4))(3) and related mononuclear complexes
      [Cu(dien)(H(2)O)](ClO(4))(2), [Cu(dien)(Him)](ClO(4))(2) were synthesized with
      diethylenetriamine (dien) as capping ligand. The crystal structure of mononuclear
      [Cu(dien)(Him)](ClO(4))(2) and binuclear complex [(dien)Cu(mu
      im)Cu(dien)](ClO(4))(3) have been determined by single crystal X-ray diffraction
      methods. The mononuclear complex [Cu(dien)(Him)](ClO(4))(2) crystallizes in the
      orthorhombic, Pca2(1) with a = 9.3420(9) A, b = 12.3750(9) A, c = 14.0830(9) A,
      beta = 90.000(7)(o) and Z = 4 and binuclear complex [(dien)Cu(mu
      im)Cu(dien)](ClO(4))(3) crystallizes in the monoclinic space group P2(1)/a, with
      a = 15.017(7) A, b = 11.938(6) A, c = 15.386(6) A, beta = 110.30(4)(o) and Z = 4.
      The molecular structures show that copper(II) ions in an asymmetrically elongated
      octahedral coordination (type 4 + 1 + 1) and in binuclear complex Cu(1) atom has
      a asymmetrically elongated octahedral coordination (type type 4 + 1 + 1) and
      Cu(2) atom exhibits a square base pyramidal coordination (type 4 + 1). The
      bridging ligand (imidazolate ion, im) lies nearly on a straight line between two
      Cu(2+), which are separated by 5.812 A, slightly shorter than the value in copper
      copper superoxide dismutase (Cu(2)-Cu(2)SOD). Magnetic measurements and electron
      spin resonance (ESR) spectroscopy of the binuclear complex have shown an
      antiferromagnetic exchange interaction. From pH-dependent cyclic voltametry (CV)
      and electronic spectroscopic studies the complex has been found to be stable over
      a wide pH range (7.75-12.50).

PMID- 15556453
TI  - The effect of memory in the stochastic master equation analyzed using the
      stochastic Liouville equation of motion. Electronic energy migration transfer
      between reorienting donor-donor, donor-acceptor chromophores.
AB  - This paper discusses the process of energy migration transfer within
      reorientating chromophores using the stochastic master equation (SME) and the
      stochastic Liouville equation (SLE) of motion. We have found that the SME over
      estimates the rate of the energy migration compared to the SLE solution for a
      case of weakly interacting chromophores. This discrepancy between SME and SLE is
      caused by a memory effect occurring when fluctuations in the dipole-dipole
      Hamiltonian (H(t)) are on the same timescale as the intrinsic fast transverse
      relaxation rate characterized by (1/T(2)). Thus the timescale critical for energy
      transfer experiments is T(2) approximately 10(-13) s. An extended SME is
      constructed, accounting for the memory effect of the dipole-dipole Hamiltonian
      dynamics. The influence of memory on the interpretation of experiments is
      discussed.

PMID- 15556454
TI  - Study on the stability of adrenaline and on the determination of its acidity
      constants.
AB  - In this work, the results are presented concerning the influence of time on the
      spectral behaviour of adrenaline (C(9)H(13)NO(3)) (AD) and of the determination
      of its acidity constants by means of spectrophotometry titrations and point-by
      point analysis, using for the latter freshly prepared samples for each analysis
      at every single pH. As the catecholamines are sensitive to light, all samples
      were protected against it during the course of the experiments. Each method
      rendered four acidity constants corresponding each to the four acid protons
      belonging to the functional groups present in the molecule; for the point-by
      point analysis the values found were: log beta(1) = 38.25 +/- 0.21, log beta(2) =
      29.65 +/- 0.17, log beta (3) = 21.01 +/- 0.14, log beta(4) = 11.34 +/- 0.071.

PMID- 15556455
TI  - Evaluation of the acidity constants of the 4-hidroxy-5-[salicylideneamino]-2-7
      naphthalenedisulfonic acid (Azomethine-H) using UV-vis spectrophotometry.
AB  - The time stability of the azomethine-H species was determined not to be better
      than 10 min in the absence of oxygen and light, however under phosphate buffered
      conditions the azomethine-H species remained stable for longer periods, as
      indicated by the spectrophotometric behaviour. Nevertheless, the analysis time
      still exceeded the stability allowance. Therefore, the determination of the
      acidity constants of the Azomethine-H species was studied by means of UV-vis
      spectrophotometry in buffered media by means of the point-by-point analysis and
      data processing with SQUAD to refine the resulting constants, which were: pK(a1)
      = 3.39, pK(a2) 7.36 and pK(a3) 8.73. The latter were associated to the
      corresponding acid-base equilibria of the amine and hydroxy groups constituting
      the molecule.

PMID- 15556456
TI  - Supramolecular interactions of [60]- and [70]fullerenes with calix[n]arenes.
AB  - [60]- and [70]fullerenes have been shown to form 1:1 supramolecular complexes
      with (i) 24,26-dimethoxy-25,27-dihydroxy-5,11,17,23-tetra(4-tert
      butyl)calix[4]arene (1) and (ii) 37,39,41-trimethoxy-38,40,42-trihydroxy
      5,11,17,23,29,35-hexa(4-tert-butyl)calix[6]arene (2) in CCl(4) medium by
      absorption spectroscopy. Charge transfer absorption bands of the complexes have
      been located in each of the cases (except [70]fullerene-2 complex) studied from
      which the vertical ionisation potential of 1 has been obtained. Formation
      constants of the complexes have been determined at four different temperatures
      from which the enthalpies and entropies of formation of the complexes have been
      obtained. Moreover, the formation constant of [70]fullerene-2 complex is higher
      than that of the [60]fullerene-1 and [60]fullerene-2 complexes at all the four
      temperatures studied. This has been accounted in terms of greater cavity size of
      2 which is a calix[6]arene compared to 1 which is a calix[4]arene and also by the
      fact that a high degree of preorganisation takes place in case of 2 through
      intramolecular H-bonding at its lower rim.

PMID- 15556457
TI  - Synthesis and spectral characterization of ternary complexes of oxovanadium(IV)
      containing some acid hydrazones and 2,2'-bipyridine.
AB  - An interesting series of heterocyclic base adducts of oxovanadium(IV) complexes
      have been synthesized by the reaction of vanadium(IV) oxide acetylacetonate with
      some hydrazones (H(2)L) in the presence of a heterocyclic base 2,2'-bipyridine.
      The compounds were characterized by analytical and different physico-chemical
      techniques like IR, electron paramagnetic resonance (EPR) and UV-Vis spectral
      studies and magnetic studies. The EPR spectra indicate that the free electron is
      in the d(xy) orbital. The coordination geometry around oxovanadium(IV) in all
      complexes is octahedral, with one dibasic tridentate ligand L(2-), and one
      bidentate heterocyclic base. The IR spectra suggest that coordination takes place
      through azomethine nitrogen and enolate oxygen from the hydrazide moiety and
      phenolate oxygen. The pyridyl nitrogens of the hydrazones, H(2)L(2) and H(2)L(4)
      are not involved in the coordination. The molar conductivities show that all the
      complexes are non-electrolytes. All electronic transitions were assigned. All the
      compounds are paramagnetic. EPR studies of all compounds suggest axial symmetry.
      The calculated bonding parameters indicate that in-plane sigma bonding is more
      covalent than in-plane pi bonding.

PMID- 15556458
TI  - Fourier-transform infrared spectrum of aspartate hydroxo-aqua nickel (II) complex
      and DFT-B3LYP/3-21G and 6-311G structural and vibrational calculations.
AB  - Aspartate hydroxo-aqua nickel (II) complex was synthesized and the structural
      analysis was carried out through the following methods: determination of the C,
      N, O and H contents, thermogravimetry and infrared spectrum. Several hypothetic
      structures were calculated by means of DFT: B3LYP/3-21G and B3LYP/6-311G quantum
      mechanical method. For [Ni(Asp)(OH)(H(2)O)] we have obtained the minimum of
      energy and no imaginary frequencies in the calculated infrared spectrum.
      Moreover, the experimental FT-infrared spectrum shows that the two N-H stretching
      follow the Bellamy-Williams relation proposed for primary amines. Coordination
      water bands were also observed in the infrared spectrum. For reasons of
      accomplishment, the Fourier transforms infrared and Raman spectra of acid
      aspartic were also discussed.

PMID- 15556459
TI  - Effect of poly(vinylidene fluoride) on solvation of NaSCN in PEO.
AB  - The blend-based electrolyte, polyethylene oxide (PEO)-poly(vinylidene fluoride)
      (PVdF)-NaSCN, was prepared and characterized by FT-IR, X-ray diffraction (XRD)
      and differential thermal analysis (DTA) measurements at room temperature, and the
      effect of PVdF content on solvation and ion association was discussed over the
      content of 5-95%. It is shown that PEO has much stronger ability of solvation to
      NaSCN than PVdF does, indicating that the polymeric donor number is more
      important than its dielectric constant in solvating effect of polymer. However,
      PVdF can keep its semicrystalline nature and form microporous structure in blend
      based electrolytes. These characters make PVdF not only enhance the mechanical
      stability of the electrolyte thin films, but also transform PEO crystalline phase
      into fully amorphous phase. Although PVdF can effectively disrupt the crystalline
      complex P(EO)(3)NaSCN, it does not affect the component of triple aggregations.
      In addition, the effect of PVdF content on ion association is also discussed in
      PEO-NaSCN electrolytes.

PMID- 15556460
TI  - Band intensity in the IR spectra and conformations of calix[4]arene and
      thiacalix[4]arene.
AB  - The experimental IR and Far IR spectra of the calix[4]arene, p-tert
      butylcalix[4]arene, thialcalix[4]arene and p-tert-butylthiacalix[4]arene were
      examined at different temperatures and interpreted. The band frequencies and
      intensities in the IR spectra of the calix[4]arene and thialcalix[4]arene were
      calculated. The absorption curves of the four possible calix[4]arene
      conformations: cone, partial cone, 1,2- and 1,3-alternate were computed. The
      bands characteristic for each conformation are defined and assigned. The obtained
      spectra-structure correlation can be used for the characteristic of calixarenes
      conformation.

PMID- 15556463
TI  - Microchimerism in immune competent patients related to the leukocyte content of
      transfused red blood cell concentrates.
AB  - BACKGROUND: Microchimerism may play a part in transfusion complications. The aim
      of this study was to examine whether establishment of post-transfusion
      microchimerism was related to leukocyte content. METHODS: Twenty non-pregnant
      female patients, without known malignant or immunological diseases, mean age 68
      years, receiving 2-4 units of red blood cell concentrates during elective
      surgery, were included. One or two of the units were from male donors. Ten
      patients received buffy-coat depleted red blood cell concentrates, leukocyte
      count 108-109 per unit, and 10 patients received red blood cells leukoreduced by
      prestorage leukocyte filtration, with a leukocyte count of <106 per unit. EDTA
      samples were collected in vacuum tubes before and after 1 week and 6 months after
      transfusion. The tubes were frozen and stored at -400 degrees C. Genomic DNA was
      isolated and PCR performed using four primer sets amplifying markers on the Y
      chromosome. RESULTS: Microchimerism was detected in a total of eight out of the
      20 patients. In three patients microchimerism was detected only before
      transfusion. These patients had given birth to one or two boys each, and had no
      history of previous transfusion. Two patients receiving buffy-coat depleted red
      blood cell concentrates and two patients receiving leukoreduced red blood cell
      concentrates had detectable microchimerism 1 week after transfusion. The age of
      the transfused red blood cell concentrates was 6, 24, 8 and 7 days, respectively.
      One patient receiving leukoreduced red blood cell concentrates had detectable
      microchimerism after 6 months. The age of this concentrate was 22 days.
      DISCUSSION: This study demonstrates that microchimerism after transfusion does
      not seem to be dose dependent, and can be induced even by a >3 week old
      leukoreduced red blood cell concentrate with a very low leukocyte content.

PMID- 15556464
TI  - Guidelines for transfusion in Norway.
AB  - The Norwegian guidelines for transfusion are harmonised in terms of standards
      with the European directives, but we have two areas where there are substantial
      differences. First, in Norway a blood donor is defined as a patient in legal
      terms. Secondly, we have stricter criteria for geographical origin of the people
      who are allowed to donate blood than most other countries. It is a challenge to
      provide information stating that these guidelines are related to the risk of
      transmitting infectious disease rather than discrimination. Increased focus on
      hemovigilance and closer contact between the blood banks and the national health
      authorities will be major issues in future work to improve the quality of
      Transfusion Medicine in Norway.

PMID- 15556465
TI  - Clinical implications of red blood cell and platelet storage lesions: an
      overview.
AB  - Both red blood cells and platelets undergo lesions upon storage which affect
      their function and possibly their clinical outcome. Some of these lesions are
      reversible, others not. Improved additive solutions and leukocyte depletion can
      delay the appearance of storage lesions. In addition, cellular apoptosis leads to
      numerous mitochondrial and surface changes during storage which have the
      potential to induce immune suppression by tuning down the innate immune system.
      This overview highlights some laboratory and clinical aspects of red cell and
      platelet storage lesions.

PMID- 15556466
TI  - Transient anti rhesus alloantibody produced by graft after non-myeloablative
      allogeneic stem cell transplant.
AB  - BACKGROUND: We report the case of a patient who received an allogeneic transplant
      with peripheral blood compatible ABO, Rhesus mismatched progenitor cells and who
      developed an asymptomatic transient anti Rhesus alloimmunisation. CASE REPORT: A
      56-year-old man with renal cell carcinoma received a non-myeloablative allogeneic
      PBPC ABO compatible graft from his HLA-identical brother. Graft-versus-host
      disease prophylaxis consisted of cyclosporine alone. On day + 59, prior to any
      transfusion, a positive direct antiglobulin test (IgG++, C3d-) was detected. The
      indirect antiglobulin test (IAT) was considered doubtful, and IAT identification
      revealed the presence of an active anti Rhesus antibody (anti D specificity) in
      the patient's serum. This immunisation had no clinical consequence, with no acute
      hemolytic episode. Further monitoring showed negative antibody screening tests on
      day + 78. CONCLUSION: To our knowledge this is the first reported case of
      transient anti Rh (D) allo-immunisation after non-myeloablative allogeneic
      peripheral blood progenitor cell (PBPC) transplant. The period of occurrence and
      the specificity of this antibody strongly suggest a donor cell origin.

PMID- 15556467
TI  - Comparison of central venous catheterization with and without ultrasound guide.
AB  - PURPOSE: To compare the effectiveness, safety and time needed to perform central
      venous catheterization (CVC) in the presence or absence of an ultrasound (US)
      guide. METHODS: Between January 1999 and February 2002 we performed CVCs in 196
      patients: 105 patients received US guided CVC (group I) and 91 patients had CVC
      without US guide (group II). RESULTS: The average time to perform CVC was shorter
      with US guide (4 vs 7 min). The utilization of the US guide was also associated
      with improved success (98.09% vs 91.2%, p<0.025) and lack of major complications
      (0% vs 9.8%, p<0.001). CONCLUSIONS: US-guided CVC affords an easier, safer and
      more rapid cannulation of a central vein. It is especially helpful in those
      patients with anatomical variation or difficult veins (small or not visible, non
      palpable landmarks) and in those with coagulative disorders.

PMID- 15556468
TI  - Efficient and safe stem cell apheresis.

PMID- 15556469
TI  - Apheresis techniques for collection of peripheral blood progenitor cells.
AB  - The combination of effective mobilisation protocols and efficient use of
      apheresis machines has caused peripheral blood progenitor cells (PBPC)
      transplantation to grow rapidly. The development of apheresis technology has
      improved over the years. Today PBSC procedures have changed towards systems to
      minimise operator interaction and to reduce the collection of undesired cells
      such as polymorphonuclear cells and platelets using functionally closed, sterile
      environments for PBSC collection in keeping with Good Manufacturing Practice
      guidelines. Blood cell separators with continuous flow technique allow the
      processing of more blood than intermittent flow devices resulting in higher PBSC
      yields. Large volume leukapheresis with the processing of 3-4-fold
      donor's/patient's blood volume can increase the number of collected progenitor
      cells. Therefore, intermittent flow cell separators are indicated if only single
      vein access is available. Anticoagulant induced hypocalcaemia is an often
      observed side effect in long lasting PBPC harvesting and monitoring of
      electrolytes should be performed especially at the end of the apheresis procedure
      to supplement low levels of potassium, calcium or magnesium. Refinement and
      improvement of collection techniques continue to add to the armamentarium of
      current approaches for cancer and non-malignant conditions and will enable future
      strategies.

PMID- 15556470
TI  - Risks and methods for peripheral blood progenitor cell collection in small
      children.
AB  - Peripheral blood progenitor cells (PBPC) are increasingly used as a source of
      stem cells for either autologous or allogeneic hematopoietic transplantation in
      children. Although technically similar to adult procedures, apheresis in small
      children worries some operators and physicians that have little experience in
      managing pediatric patients or donors. However several published series have
      showed that these procedures, when performed by experienced teams are safe and
      can obtain enough amount of PBPC for either autologous or allogeneic
      hematopoietic transplantation. Some technical aspects must be considered in
      pediatric apheresis due to the size of the patient/donor. Factors that must be
      evaluated are extracorporeal circuit volume, blood flow rates, type of
      anticoagulant and vascular access. Other important issue to be considered is the
      emotional stress for them and their relatives. Leukaphereses in children may be
      performed with any of the reported continuous blood cell separator without
      sedation. Adverse events are mainly related either to vascular access or to
      metabolic or hemodynamic changes. Anyway, taking all these complications
      together, they are not higher than those adverse events or toxicities reported
      after general anesthesia and bone marrow harvesting.

PMID- 15556471
TI  - PBSC mobilization.
AB  - Intentional recruitment of hematopoietic stem cells from bone marrow to
      peripheral blood is a clinical process termed peripheral blood stem cell (PSBC)
      mobilization. Mobilized PSBC has replaced bone marrow as the preferred source of
      stem cells for patients undergoing high-dose chemotherapy because of rapid and
      durable engraftment and reconstitution of functional bone marrow. Although the
      mechanism involved in the process of PBSC mobilization by cytokines is largely
      unknown, granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy
      combined with GCSF is used as a mobilizing agent in current clinical practice. To
      date, G-CSF is the best cytokine for PBSC mobilization. However, there are some
      controversies in its efficacy (poor mobilizer) and safety (in allogeneic donors).
      Recent research progress has revealed some part of the mechanistic scenarios of
      PBSC mobilization and found promising candidates for the agents for PBSC
      mobilization. Until the research at molecular and cellular levels elucidates the
      precise mechanisms, collecting and comparing clinical observations is the best
      way to find more optimal condition for PBSC mobilization.

PMID- 15556472
TI  - Factors for PBPC collection efficiency and collection predictors.
AB  - Factors affecting collection efficiency of peripheral blood stem cells (PBSCs)
      include patient's age, diagnosis, preceding chemoradiotherapy, disease invasion
      of the bone marrow and mobilizing chemotherapy in PBSC collection for autologous
      transplants. Mobilizing cytokines, timing for apheresis, machines and operating
      software would affect mobilization and collection of PBSCs both for autologous
      and allogeneic transplantation. Also donor's age and gender would affect PBSC
      yield for allogeneic transplantation. Surrogate markers including peripheral
      blood CD34+ cell counts before mobilization and on day of collection have been
      reported to predict the yield of PBSC harvest. A number of standard procedures
      have been developed based on these findings. Newer agents for PBSC mobilization
      are being evaluated and still other factors affecting mobilization are being
      sought to better predict and cope with poor mobilization.

PMID- 15556473
TI  - A molecular model for transcription in the RNA world based on the ribosome large
      subunit.
AB  - Examination of the tRNA binding sites in the ribosome suggests that it might once
      have been able to catalyse the polymerisation of RNA. Based on a viral RNA
      dependant RNA polymerase, the geometry of a potential active site for this
      ribopolymerase was constructed. From examination of the active site geometry,
      along with other arguments, it is suggested that the ribopolymerase synthesised a
      parallel complementary strand. When combined into a dimeric polymerase, this
      strategy minimises the exposure of single-stranded RNA and prevents self
      hybridisation: both previously difficult problems for the RNA world hypothesis.

PMID- 15556474
TI  - Quantitative methods for ecological network analysis.
AB  - The analysis of networks of ecological trophic transfers is a useful complement
      to simulation modeling in the quest for understanding whole-ecosystem dynamics.
      Trophic networks can be studied in quantitative and systematic fashion at several
      levels. Indirect relationships between any two individual taxa in an ecosystem,
      which often differ in either nature or magnitude from their direct influences,
      can be assayed using techniques from linear algebra. The same mathematics can
      also be employed to ascertain where along the trophic continuum any individual
      taxon is operating, or to map the web of connections into a virtual linear chain
      that summarizes trophodynamic performance by the system. Backtracking algorithms
      with pruning have been written which identify pathways for the recycle of
      materials and energy within the system. The pattern of such cycling often reveals
      modes of control or types of functions exhibited by various groups of taxa. The
      performance of the system as a whole at processing material and energy can be
      quantified using information theory. In particular, the complexity of process
      interactions can be parsed into separate terms that distinguish organized,
      efficient performance from the capacity for further development and recovery from
      disturbance. Finally, the sensitivities of the information-theoretic system
      indices appear to identify the dynamical bottlenecks in ecosystem functioning.

PMID- 15556475
TI  - Phylogenetic distribution of DNA-binding transcription factors in bacteria and
      archaea.
AB  - We have addressed the distribution and abundance of 75 transcription factor (TF)
      families in complete genomes from 90 different bacterial and archaeal species. We
      found that the proportion of TFs increases with genome size. The deficit of TFs
      in some genomes might be compensated by the presence of proteins organizing and
      compacting DNA, such as histone-like proteins. Nine families are represented in
      all the bacteria and archaea we analyzed, whereas 17 families are specific to
      bacteria, providing evidence for regulon specialization at an early stage of
      evolution between the bacterial and archeal lineages. Ten of the 17 families
      identified in bacteria belong exclusively to the proteobacteria defining a
      specific signature for this taxonomical group. In bacteria, 10 families are lost
      mostly in intracellular pathogens and endosymbionts, while 9 families seem to
      have been horizontally transferred to archaea. The winged helix-turn-helix (HTH)
      is by far the most abundant structure (motif) in prokaryotes, and might have been
      the earliest HTH motif to appear as shown by its distribution and abundance in
      both bacterial and archaeal cellular domains. Horizontal gene transfer and
      lineage-specific gene losses suggest a progressive elimination of TFs in the
      course of archaeal and bacterial evolution. This analysis provides a framework
      for discussing the selective forces directing the evolution of the
      transcriptional machinery in prokaryotes.

PMID- 15556476
TI  - The influence of gapped positions in multiple sequence alignments on secondary
      structure prediction methods.
AB  - All currently leading protein secondary structure prediction methods use a
      multiple protein sequence alignment to predict the secondary structure of the top
      sequence. In most of these methods, prior to prediction, alignment positions
      showing a gap in the top sequence are deleted, consequently leading to shrinking
      of the alignment and loss of position-specific information. In this paper we
      investigate the effect of this removal of information on secondary structure
      prediction accuracy. To this end, we have designed SymSSP, an algorithm that post
      processes the predicted secondary structure of all sequences in a multiple
      sequence alignment by (i) making use of the alignment's evolutionary information
      and (ii) re-introducing most of the information that would otherwise be lost. The
      post-processed information is then given to a new dynamic programming routine
      that produces an optimally segmented consensus secondary structure for each of
      the multiple alignment sequences. We have tested our method on the state-of-the
      art secondary structure prediction methods PHD, PROFsec, SSPro2 and JNET using
      the HOMSTRAD database of reference alignments. Our consensus-deriving dynamic
      programming strategy is consistently better at improving the segmentation quality
      of the predictions compared to the commonly used majority voting technique. In
      addition, we have applied several weighting schemes from the literature to our
      novel consensus-deriving dynamic programming routine. Finally, we have
      investigated the level of noise introduced by prediction errors into the
      consensus and show that predictions of edges of helices and strands are half the
      time wrong for all the four tested prediction methods.

PMID- 15556477
TI  - Comparing two K-category assignments by a K-category correlation coefficient.
AB  - Predicted assignments of biological sequences are often evaluated by Matthews
      correlation coefficient. However, Matthews correlation coefficient applies only
      to cases where the assignments belong to two categories, and cases with more than
      two categories are often artificially forced into two categories by considering
      what belongs and what does not belong to one of the categories, leading to the
      loss of information. Here, an extended correlation coefficient that applies to K
      categories is proposed, and this measure is shown to be highly applicable for
      evaluating prediction of RNA secondary structure in cases where some predicted
      pairs go into the category "unknown" due to lack of reliability in predicted
      pairs or unpaired residues. Hence, predicting base pairs of RNA secondary
      structure can be a three-category problem. The measure is further shown to be
      well in agreement with existing performance measures used for ranking protein
      secondary structure predictions. Server and software is available at
      http://rk.kvl.dk/.

PMID- 15556478
TI  - Antagonist binding in the rat muscarinic receptor A study by docking and X-ray
      crystallography.
AB  - A series of agonists to the rat muscarinic receptor have been docked
      computationally to the active site of a homology model of rat M1 muscarinic
      receptor. The agonists were modelled on the X-ray crystal structure of atropine,
      which is reported here and the docking studies are shown to reproduce correctly
      the order of experimental binding affinities for the agonists as well as indicate
      where there appear to be inconsistencies in the experimental data. The crystal
      and molecular structure of atropine (tropine tropate; alpha
      [hydroxymethyl]benzeneacetic acid 8-methyl[3.2.1]oct-3-yl ester C17H23NO3) has
      been determined by X-ray crystallography using an automated Patterson search
      method, and refined by full-matrix least-squares to a final R of 0.0452 for 2701
      independent observed reflections and 192 parameters using Mo Kalpha radiation,
      lambda=0.71073A at 150K. The compound crystallises in space group Fdd2 with Z=16
      molecules per unit cell.

PMID- 15556479
TI  - Retrieving definitional content for ontology development.
AB  - Ontology construction requires an understanding of the meaning and usage of its
      encoded concepts. While definitions found in dictionaries or glossaries may be
      adequate for many concepts, the actual usage in expert writing could be a better
      source of information for many others. The goal of this paper is to describe an
      automated procedure for finding definitional content in expert writing. The
      approach uses machine learning on phrasal features to learn when sentences in a
      book contain definitional content, as determined by their similarity to glossary
      definitions provided in the same book. The end result is not a concise definition
      of a given concept, but for each sentence, a predicted probability that it
      contains information relevant to a definition. The approach is evaluated
      automatically for terms with explicit definitions, and manually for terms with no
      available definition.

PMID- 15556480
TI  - An unusual 500,000 bases long oscillation of guanine and cytosine content in
      human chromosome 21.
AB  - An oscillation with a period of around 500 kb in guanine and cytosine content
      (GC%) is observed in the DNA sequence of human chromosome 21. This oscillation is
      localized in the rightmost one-eighth region of the chromosome, from 43.5 Mb to
      46.5 Mb. Five cycles of oscillation are observed in this region with six GC-rich
      peaks and five GC-poor valleys. The GC-poor valleys comprise regions with low
      density of CpG islands and, alternating between the two DNA strands, low gene
      density regions. Consequently, the long-range oscillation of GC% result in
      spacing patterns of both CpG island density, and to a lesser extent, gene
      densities.

PMID- 15556481
TI  - Development of KiBank, a database supporting structure-based drug design.
AB  - KiBank is a database of inhibition constant (Ki) values with 3D structures of
      target proteins and chemicals. Ki values were accumulated from peer-reviewed
      literature searched via PubMed. The 3D structure files of target proteins were
      originally from Protein Data Bank (PDB), while the 2D structure files of the
      chemicals were collected together with the Ki values and then converted into 3D
      ones. In KiBank, the chemical and protein 3D structures with hydrogen atoms were
      optimized by energy minimization and stored in MDL MOL and PDB format,
      respectively. KiBank is designed to support structure-based drug design. It
      provides structure files of proteins and chemicals ready for use in virtual
      screening through automated docking methods, while the Ki values can be applied
      for tests of docking/scoring combinations, program parameter settings, and
      calibration of empirical scoring functions. Additionally, the chemical structures
      and corresponding Ki values in KiBank are useful for lead optimization based on
      quantitative structure-activity relationship (QSAR) techniques. KiBank is updated
      on a daily basis and is freely available at . As of August 2004, KiBank contains
      8000 Ki values, over 6000 chemicals and 166 proteins covering the subtypes of
      receptors and enzymes.

PMID- 15556482
TI  - iProLINK: an integrated protein resource for literature mining.
AB  - The exponential growth of large-scale molecular sequence data and of the PubMed
      scientific literature has prompted active research in biological literature
      mining and information extraction to facilitate genome/proteome annotation and
      improve the quality of biological databases. Motivated by the promise of text
      mining methodologies, but at the same time, the lack of adequate curated data for
      training and benchmarking, the Protein Information Resource (PIR) has developed a
      resource for protein literature mining--iProLINK (integrated Protein Literature
      INformation and Knowledge). As PIR focuses its effort on the curation of the
      UniProt protein sequence database, the goal of iProLINK is to provide curated
      data sources that can be utilized for text mining research in the areas of
      bibliography mapping, annotation extraction, protein named entity recognition,
      and protein ontology development. The data sources for bibliography mapping and
      annotation extraction include mapped citations (PubMed ID to protein entry and
      feature line mapping) and annotation-tagged literature corpora. The latter
      includes several hundred abstracts and full-text articles tagged with
      experimentally validated post-translational modifications (PTMs) annotated in the
      PIR protein sequence database. The data sources for entity recognition and
      ontology development include a protein name dictionary, word token dictionaries,
      protein name-tagged literature corpora along with tagging guidelines, as well as
      a protein ontology based on PIRSF protein family names. iProLINK is freely
      accessible at http://pir.georgetown.edu/iprolink, with hypertext links for all
      downloadable files.

PMID- 15556483
TI  - A hierarchical clustering algorithm for MIMD architecture.
AB  - Hierarchical clustering is the most often used method for grouping similar
      patterns of gene expression data. A fundamental problem with existing
      implementations of this clustering method is the inability to handle large data
      sets within a reasonable time and memory resources. We propose a parallelized
      algorithm of hierarchical clustering to solve this problem. Our implementation on
      a multiple instruction multiple data (MIMD) architecture shows considerable
      reduction in computational time and inter-node communication overhead, especially
      for large data sets. We use the standard message passing library, message passing
      interface (MPI) for any MIMD systems.

PMID- 15556485
TI  - Recent advances in analysis of Chinese medical plants and traditional medicines.
AB  - Chinese herbal medicine is gaining increasing popularity worldwide for health
      promotion and adjuvant therapy. Thus, selective and efficient analytical methods
      are required not only for quality assurance but also for authentication of the
      plant material. Applications of both chromatographic and electrophoretic
      techniques to the analysis of medicinal plants and Chinese traditional medicine
      preparations over the last 3 years are outlined in this review. The role of
      chemical fingerprinting is highlighted and a brief survey of determination of
      toxic components, natural and synthetic adulterants is also included. Moreover,
      different sample pretreatment and extraction methods are discussed.

PMID- 15556486
TI  - Extraction methods and chemical standardization of botanicals and herbal
      preparations.
AB  - Botanicals and herbal preparations are medicinal preparations, containing a
      single or two or more medicinal plants. The focus of this review paper is on the
      analytical methodologies, which included the combination of sample preparation
      tools and chromatographic techniques for the chemical standardization of marker
      compounds or active ingredients in botanicals and herbal preparations. The common
      problems and key challenges in the chemical standardization of botanicals and
      herbal preparations were discussed. As sample preparation is the most important
      step in the development of analytical methods for the analysis of constituents
      present in botanicals and herbal preparations, the strength and weakness of
      different extraction techniques are discussed. For the analysis of compounds
      present in the plant extracts, the applications of common chromatographic
      techniques, such as HPLC, CE, HRGC/MS, HPLC/MS and HPLC/MS/MS are discussed. The
      strength, weakness and applicability of various separation tools are stated.
      Procedures for the identification of marker or active compounds in plant
      extracts, using HPLC/MS, were proposed. Finally, the effects of batch-to-batch
      variation of the medicinal plants are investigated and discussed.

PMID- 15556487
TI  - Separation strategies of plant constituents--current status.
AB  - The paper summarizes the state of art of different separation methods which are
      used for the analysis and isolation of plant constituents. An overview about the
      extraction methods which are frequently used for the non-volatile constituents of
      plants is given. Special attention is paid to the identification possibilities of
      non-volatile and volatile compounds, since generally the role of identification
      of plant's constituents is undervalued. We would emphasize the facts that, for
      correct identification, the various chromatographic and spectroscopic methods
      have to be used in conjunction. The application of two different methods from
      each field is usually sufficient. For quantitative information, two independent
      methods are necessary and are acceptable if the results are within 3% of each
      other. If only one method is available for quantitative analysis, the results can
      only be accepted if, using the global optimum, the ratios of the components
      determined are identical to one decimal place with the ratios of three
      measurements (local optima) using different mobile phases with different
      selectivities. Based on our own 20-year experience and more than a hundred
      isolated compounds, we give an isolation strategy where the structures and
      properties of the compounds to be isolated do not have to be known. It is pointed
      out that without analytical monitoring, the results of preparative separations
      cannot be guaranteed.

PMID- 15556488
TI  - Quality control of herbal medicines.
AB  - Different chromatographic and electrophoretic techniques commonly used in the
      instrumental inspection of herbal medicines (HM) are first comprehensively
      reviewed. Chemical fingerprints obtained by chromatographic and electrophoretic
      techniques, especially by hyphenated chromatographies, are strongly recommended
      for the purpose of quality control of herbal medicines, since they might
      represent appropriately the "chemical integrities" of the herbal medicines and
      therefore be used for authentication and identification of the herbal products.
      Based on the conception of phytoequivalence, the chromatographic fingerprints of
      herbal medicines could be utilized for addressing the problem of quality control
      of herbal medicines. Several novel chemometric methods for evaluating the
      fingerprints of herbal products, such as the method based on information theory,
      similarity estimation, chemical pattern recognition, spectral correlative
      chromatogram (SCC), multivariate resolution, etc. are discussed in detail with
      examples, which showed that the combination of chromatographic fingerprints of
      herbal medicines and the chemometric evaluation might be a powerful tool for
      quality control of herbal products.

PMID- 15556489
TI  - Strategy for analysis and screening of bioactive compounds in traditional Chinese
      medicines.
AB  - Traditional Chinese medicines (TCMs), due to their long time clinic test and
      reliable therapeutic efficacy, are attracting increased global attention served
      as excellent pools of bioactive compounds for the discovery of new drugs.
      However, hundreds or even thousands of components are usually contained in
      traditional Chinese medicines and only a few compounds are responsible for the
      pharmaceutical and/or toxic effects. The large numbers of other components in
      traditional Chinese medicines make the screening and analysis of the bioactive
      components extremely difficult. By the way, the combination effect of bioactive
      components on the pharmacological activity makes it very difficult to clear the
      therapeutic mechanism of TCMs. Therefore, some strategies have to design for
      screening of bioactive compounds in traditional Chinese medicines, which further
      leads to disclose the therapeutic mechanism of TCMs in molecular level. The
      review will summarize the present state of the art of screening strategy for
      active compounds in traditional Chinese medicines, and the chromatography methods
      for screening and analysis of bioactive compounds in traditional Chinese
      medicines will be emphasized.

PMID- 15556490
TI  - Separation procedures for naturally occurring antioxidant phytochemicals.
AB  - Phytochemicals in fruits, vegetables, spices and traditional herbal medicinal
      plants have been found to play protective roles against many human chronic
      diseases including cancer and cardiovascular diseases (CVD). These diseases are
      associated with oxidative stresses caused by excess free radicals and other
      reactive oxygen species. Antioxidant phytochemicals exert their effect by
      neutralizing these highly reactive radicals. Among the tens of thousands of
      phytochemicals found in our diets or traditional medicines, polyphenols and
      carotenoids stand out as the two most important groups of natural antioxidants.
      However, although collectively these phytochemicals are good antioxidants, the
      roles and effect of individual compounds are often not well known. Hundreds of
      carotenoids and thousands of polyphenols have been identified so far from various
      plants. A single plant could contain highly complex profiles of these compounds,
      which sometimes are labile to heat, air and light, and they may exist at very low
      concentrations in the plants. This makes the separation and detection of these
      antioxidant phytochemicals a challenging task. The present review focuses on the
      antioxidant activity, chemical types, sampling and sample processing procedures,
      and separation using various chromatographic and electrophoretic techniques.
      Detection and quantification using ultraviolet-visible-diode array and mass
      spectrometry will be discussed.

PMID- 15556491
TI  - Separation methods for antibacterial and antirheumatism agents in plant
      medicines.
AB  - Traditional oriental medicines (TOM), with a very long history and many
      remarkable features, are very popular in Asian countries, especially in China,
      Japan and Korea. With the development of advanced analytical techniques, the
      modernization of traditional medicine has become a hot area in recent years and
      some herbal medicines have been increasingly accepted in western countries.
      Separation and determination of active components in various herbal medicines are
      considered to be critical for the modernization process. Antibacterial and
      antirheumatism agents are widely distributed in many medical plants and commonly
      used in clinical treatment. Therefore, the development of effective separation
      methods for the quality control of herbal medicines is absolutely important. In
      this article, the separation methods for the analysis of antibacterial and
      antirheumatism compounds in TOM were reviewed, including thin layer
      chromatography (TLC), gas chromatography (GC), supercritical fluid chromatography
      (SFC), high-performance liquid chromatography (HPLC), capillary electrophoresis
      (CE) and related hyphenation techniques. Sample preparation procedures and
      further development of these methods were also discussed.

PMID- 15556492
TI  - Analysis methods of ginsenosides.
AB  - Ginsenosides are considered the main active principles of the famous Chinese
      traditional medicine "ginseng". For more than 30 years many researchers developed
      methods for the identification and quantification of ginsenosides in ginseng
      plant material, extracts and products. Separation of ginsenosides has been
      achieved using thin layer chromatography (TLC), gas chromatography (GC) and high
      performance liquid chromatography (HPLC). Among these techniques HPLC is by far
      the most employed. Ultraviolet (UV), evaporative light scattering (ELSD),
      fluorescence and, recently, mass spectrometry (MS) were coupled with HPLC for the
      detection of ginsenosides. The most recent methods are here discussed together
      with a critical evaluation of the published results. Furthermore new techniques
      such as near infrared spectroscopy (NIRS) and enzyme immunosassay (EIA) recently
      used for the determination of ginsenosides will be discussed.

PMID- 15556493
TI  - Separation and isolation methods for analysis of the active principles of Sho
      saiko-to (SST) oriental medicine.
AB  - Sho-saiko-to (SST) was introduced into Japan as an oriental classical medicine
      from China approximately 1500 years ago, and it is currently the most
      representative Kampo medicine (traditional Japanese medicine). SST is
      manufactured in Japan as an ethical drug on a modern industrial scale in which
      the quality of ingredients is standardized with Good Manufacturing Practices
      (GMP) regulation. SST is widely used for the treatment of chronic hepatitis.
      Experimental and clinical studies including multi-center, placebo-controlled,
      double-blind studies have demonstrated the various pharmacological effects of
      SST. SST is prepared from the hot water extraction of seven raw materials,
      therefore many kinds of constituents are included. Three-dimensional (3D) HPLC
      analysis is useful for obtaining many kinds of constituents, especially low
      molecular ultraviolet (UV) quenching compounds, contained in SST as well as its
      fractions. Fingerprint pattern provided by 3D HPLC analysis makes possible to
      identify the overall-viewing of SST. Databases of UV spectra of the components of
      medicinal herbs obtained by reversed-phase (RP) HPLC using a photodiode array
      (PDA) and fingerprint patterns of crude drugs made by 3D HPLC analysis facilitate
      the identification, analysis and quality of herbal drugs. Studies using both PDA
      HPLC and an amino acid analysis with a fluorometric detector have found that SST
      contains fifteen major low molecular compounds (i.e. baicalin, wogonin-7-O
      glucuronide, liquiritin, their three aglycons, liquiritin apioside, glycyrrhizin,
      saikosaponin b1, saikosaponin b2, ginsenoside Rg1, ginsenoside Rb1, (6)-gingerol,
      (6)-shogaol and arginine). These compounds have various pharmacological actions,
      and are assumed to be responsible, at least partly, for the pharmacological
      effects of SST. Although there have only been a few investigations on high
      molecular compounds with pharmacological actions contained in SST, several kinds
      of polysaccharides have been isolated from constituent herbs of SST. This review
      paper summarizes analytical methods of separation, isolation and identification
      of compounds with biological activities from SST, which is a mixture drug of
      medicinal herbs. Accordingly, this paper would not focus on methods of
      separation, isolation and analysis of particular compounds from each constituent
      herb of SST.

PMID- 15556494
TI  - Liquid chromatography of active principles in Sophora flavescens root.
AB  - Herbal medicines were one of the major resources for healthcare in earlier
      stages, and some traditional herbal medicines have been in use for more than 2000
      years. Currently, they are attracting more and more attention of the modern
      pharmaceutical industry, as scientists has become aware that herbs have almost
      infinite resources for medicine development. This review provides an overview of
      the analytical approaches applied in the researches concentrated on various
      aspects of the matrine-type alkaloids in Sophora flavescens root. Emphasis will
      be laid on the analytical processes of high-performance liquid chromatography
      (HPLC), capillary electrophoresis (CE), as well as gas chromatography (GC)
      methods. The sample extraction, separation and detection have been summarized. In
      addition, the applications of chromatographic determinations are introduced for
      the main matrine-type alkaloids in S. flavescens root, such as matrine,
      sophoridine, sophocarpine, lehmannine, sophoramine, oxymartine, oxysophocarpine,
      cytosine and aloperine. The advantages and limitations of HPLC, CE and GC methods
      in the analytical applications of the alkaloids are also discussed.

PMID- 15556495
TI  - Separation methods for pharmacologically active xanthones.
AB  - Xanthones, as a kind of polyphenolic natural products with many strong
      bioactivities, are attractive for separation scientists due to the similarity and
      diversity of their structures resulting in difficult separation by
      chromatographic methods. High performance liquid chromatography (HPLC) and thin
      layer chromatography (TLC) are traditional methods to separate xanthones.
      Recently, capillary electrophoresis (CE), as a micro-column technique driven by
      electroosmotic flow (EOF), with its high efficiency and high-speed separation,
      has been employed to separate xanthones and determine their physicochemical
      properties such as binding constants with cyclodextrin (CD) and ionization
      constants. Since xanthones have been used in clinic treatment, the development of
      chromatographic and CE methods for the separation and determination of xanthones
      plays an essential role in the quality control of some herbal medicines
      containing xanthones. This article reviewed the separation of xanthones by HPLC,
      TLC and CE, citing 72 literatures. This review focused on the CE separation for
      xanthones due to its unique advantages compared to chromatographic methods. The
      comparison of separation selectivity of different CE modes including capillary
      zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC),
      microemulsion electrokinetic capillary chromatography (MEEKC) and capillary
      electrochromatography (CEC) was discussed. Compared with traditional
      chromatographic methods such as HPLC and TLC, CE has higher separation
      efficiency, faster separation, lower cost and more flexible modes. However,
      because of low sensitivity of UV detector and low contents of xanthones in herbal
      medicines, CE methods have seldom been applied to the analysis of real samples
      although CE showed great potential for xanthone separation. The determination of
      xanthones in herbal medicines has been often achieved by HPLC. Hence, how to
      enhance CE detection sensitivity for real sample analysis, e.g. by on-line
      preconcentration and CE-MS, would be a key to achieve the quantitation of
      xanthones.

PMID- 15556496
TI  - Separation procedures for the pharmacologically active components of rhubarb.
AB  - Rhubarb, as an important Chinese medicine, has many functions owing to containing
      anthraquinone derivatives. The analysis of anthraquinone derivatives in Chinese
      rhubarb is reviewed. The analytical techniques include high performance liquid
      chromatography, capillary electrophoresis, thin-layer chromatography and so on.
      The main operation parameters in every technique were given. The structures of
      anthraquinone derivatives and the classification of Chinese rhubarb were
      summarized too.

PMID- 15556497
TI  - Biologically active components of Physostigma venenosum.
AB  - Physostigmine is a major alkaloid found in the seeds of the fabaceous plant
      Physostigma venenosum. It is a powerful and reversible acetylcholine esterase
      inhibitor which effectively increases the concentration of acetylcholine at the
      sites of cholinergic transmission. It exerts its cholinesterase inhibitor effect
      in both the periphery and central nervous system. Many studies on physostigmine
      have involved the reliance on techniques that extract and quantify physostigmine
      in biological samples. This paper presents an overview of the currently applied
      methodologies for the determination of physostigmine and its metabolites in
      various biological samples. Papers published from January 1980 to December 2003
      were taken into consideration for the discussion of the metabolism and analytical
      method of physostigmine. HPLC methods have been discussed and used in most of the
      references cited in this review. A few CE and RIA methods that have been recently
      reported are also mentioned in this paper. Basic information about the sample
      assayed, sample preparation, chromatographic column, mobile phase, detection mode
      and validation data are summarized in a table.

PMID- 15556498
TI  - Gardenia herbal active constituents: applicable separation procedures.
AB  - Gardenia herb has been used as alternative drug for thousand years. They may
      provide therapeutic or cause toxic effect. Recently, large scale of biological
      screen, phytochemical separation, isolation, and identification were widely
      performed. Quality control of the active ingredients should be concern for the
      application of Gardenia herbs. Many systems have been developed for the
      determination of herbal ingredients. This article reviews some of the plants and
      their active constituents that have been used for medicinal applications. The
      sample preparation, separation, and determination of Gardenia herbal ingredients
      were discussed. Based on the separation, the method of gas chromatography, liquid
      chromatography, and capillary electrophoresis were also discussed.

PMID- 15556499
TI  - Analysis of kavalactones from Piper methysticum (kava-kava).
AB  - The chemical analysis and quality control of both Piper methysticum G. Forster
      (kava-kava) and extracts obtained by aqueous acetone or aqueous methanol as well
      as supercritical fluid extraction are reviewed. In the last two decades various
      procedures concerning the separation and detection of kavalactones have been
      routinely carried out by gas chromatography (without previous derivatization of
      kavalactones) and high performance liquid chromatography but most of them are not
      validated or only partially validated. Recently, analyses by supercritical fluid
      chromatography and micellar electrokinetic chromatography have also been
      reported. Both gas chromatography and high performance liquid chromatography can
      be used for the analysis of kavalactones with some advantages and disadvantages
      for each method. Using gas chromatography analysis, methysticin and yangonin,
      which are two of the major components, are generally not separated. In addition,
      the high temperature of the injection port caused the decomposition of
      methysticin. Concerning high performance liquid chromatography analyses, the
      reversed-phase is generally better because highly reproducible with a very low
      detection limit for all compounds even if the quantitative analysis of the
      kavalactones by liquid chromatography needs to be carried out in the absence of
      light to prevent the cis/trans isomerisation of yangonin.

PMID- 15556500
TI  - Separation procedures applicable to lignan analysis.
AB  - Lignans are a class of secondary plant metabolites produced by oxidative
      dimerization of two phenylpropanoid units. They have been found in many plants of
      Oriental medicine. In consequence of recent knowledge it is held that lignans are
      responsible for the key pharmacological activities of these plants. This review
      surveys the chromatographic, electromigration and hyphenated methods so far
      applied for the separation of lignans in Oriental plants used in phytotherapy as
      well as for the analyses of these lignans and their metabolites in biological
      matrices and food samples. In addition, the sample clean-up procedures--solvent
      extractions and supercritical fluid extractions--are also included.

PMID- 15556501
TI  - Chromatographic and electrophoretic methods for pharmaceutically active compounds
      in Rhododendron dauricum.
AB  - In this review, chemical constituents present in Rhododendron dauricum L. were
      briefly surveyed, and the methods of pretreatment of this plant prior to analysis
      were also summarized. The analysis methods reported for determining
      pharmaceutically active compounds in R. dauricum L. include gas chromatography
      with mass spectrscopy, thin layer chromatography (TLC), high performance liquid
      chromatography (HPLC) and capillary electrophoresis (CE). In addition, both
      advantages and disadvantages of the above methods were mentioned.

PMID- 15556502
TI  - Chromatographic and electrophoretic methods for Lingzhi pharmacologically active
      components.
AB  - Lingzhi is the Chinese name given to the Ganoderma family of mushrooms, which was
      considered the most valuable medicine in ancient China and was believed to bring
      longevity, due to its mysterious power of healing the body and calming the mind.
      Today, Lingzhi is still widely revered as a valuable health supplement and herbal
      medicine worldwide, as studies (mostly conducted in China, Korea, Japan and the
      United States) into the medicinal and nutritional values of Lingzhi revealed that
      it does indeed contain certain bioactive ingredients (such as triterpenes and
      polysaccharides) that might be beneficial for the prevention and treatment of a
      variety of ailments, including important diseases such as hypertension, diabetes,
      hepatitis, cancers, and AIDS. As research into the biological activities of
      Lingzhi, as well as the quality assurance and quality control of Lingzhi
      products, require the isolation/purification of active ingredients from Lingzhi,
      followed by subsequent analytical and/or preparative separations, the present
      review summarizes the various chromatographic and electrophoretic methods (as
      well as sample pretreatment methods) typically employed to achieve such
      extraction/separation procedures.

PMID- 15556503
TI  - Separation methods of quinonoid constituents of plants used in Oriental
      traditional medicines.
AB  - Analysis of molecular constituents of traditional Oriental medicines has acquired
      a fresh perspective in view of a surge in interest in the consumption of herbal
      prescriptions all over the world. Several of them contain quinonoid compounds,
      and the long-standing therapeutic applications of these herbs have been
      vindicated, to some extent, through recent studies on the significant
      pharmacological properties of these compounds. In fact, the bioactive quinonoids
      and their analogues often serve as the 'marker' constituents of the respective
      plants of major commercial importance. Hence, shikonin, plumbagin, diospyrin,
      emodin analogues, sennosides, hypericin, tanshinone and related compounds have
      been discussed in this review which focuses on their extraction, separation and
      analysis from plant sources, cell cultures and biological fluids. As for the
      analysis of quinonoids, high-performance liquid chromatography connected with
      various detectors (ultraviolet, photodiode array, fluorescence, mass, nuclear
      magnetic resonance) has been the most useful technology succeeding the
      conventional methods such as thin layer and column chromatography. In some cases,
      high-performance thin layer chromatography and capillary electrophoresis are also
      used for this purpose.

PMID- 15556504
TI  - Separation methods used for Scutellaria baicalensis active components.
AB  - Scutellaria baicalensis Georgi is one of the most widely used traditional Chinese
      herbal medicines. Its roots have been used for anti-inflammation, anticancer,
      antiviral and antibacterial infections of the respiratory and the
      gastrointestinal tract, cleaning away heat, moistening aridity, purging fire,
      detoxifying toxicosis, reducing the total cholesterol level and decreasing blood
      pressures. Baicalin, baicalein, wogonin and oroxylin A are its main active
      components. This review provides an overview of various separation, detection,
      and identification techniques employed for the quantitative and qualitative
      determination of these active components. Applications of high-performance liquid
      chromatography, high-speed counter-current chromatography, thin layer
      chromatography, capillary electrophoresis, and micellar electrokinetic capillary
      chromatography to the separation and determination of these active components are
      described. Examples of identification of these active components and their
      metabolites in complex matrices by high-performance liquid chromatography-mass
      spectrometry and gas chromatography-mass spectrometry are also presented. The
      advantages and limitations of these separation and identification methods are
      assessed and discussed.

PMID- 15556505
TI  - Hippophae rhamnoides L.: chromatographic methods to determine chemical
      composition, use in traditional medicine and pharmacological effects.
AB  - There is an increasing interest in the usage of chromatographic methods on the
      analysis of chemical compounds present in Hippophae rhamnoides L. In this paper,
      the chromatographic techniques applied for the determination, separation and
      identification of chemical compounds of H. rhamnoides L. are reviewed. We
      examined the existing chromatographic methods based on separations by paper and
      thin-layer chromatography, gas chromatography, high-performance liquid
      chromatography and capillary electrophoresis and also methods of detection by
      ultraviolet absorption, fluorescence, refractive index, electrochemical and mass
      spectrometry. Biological properties of the plant and its pharmacological effects
      and use in traditional medicine have also been reviewed.

PMID- 15556506
TI  - Analysis of sugars in traditional Chinese drugs.
AB  - This review is presented of chromatography and electromigration methods currently
      in use to determine sugars in traditional Chinese drugs: gas chromatography (GC),
      high-performance liquid chromatography (HPLC), ion-exchange chromatography, gel
      column chromatography (GCC), paper chromatography (PC) and thin layer
      chromatography (TLC), capillary electrophoresis (CE) and gel electrophoresis
      (GEP). The detection methods combined with above separation methods including
      ultra-violet, mass spectra, fluorescent light, refractive index (RI),
      electrochemical detection are also described. For the complicacy of structural
      analysis of polysaccharides in traditional Chinese drugs, the hyphenation
      procedures concerned with this analysis are introduced in this article too.

PMID- 15556507
TI  - Analytical methods to determine phytoestrogenic compounds.
AB  - The analytical methods for the determination of phytoestrogenic compounds in
      edible plants, plant products and biological matrices are reviewed. The
      detection, qualitative and quantitative methods based on different
      chromatographic separations of gas chromatography (GC), high-performance liquid
      chromatography (HPLC) and capillary electrophoresis (CE) coupled with various
      detections by ultraviolet absorption (UV), electrochemical detection (ED),
      fluorescence detection, mass spectrometry (MS) and nuclear magnetic resonance
      spectroscopy (NMR), as well as non-chromatographic immunoassay are each
      extensively examined and compared. An overview on phytoestrogen chemistry,
      bioactivities and health effects, plant precursors, metabolism and sample
      preparation is also presented.

PMID- 15556508
TI  - Dibenzo[a,c]cyclooctadiene lignans of the genus Schisandra: importance, isolation
      and determination.
AB  - The drug Wuweizi (dried fruits of Schisandra chinensis or S. sphenantherd) is one
      of important medicinal means used in the Oriental medicine. The lignans of
      dibenzo[a,c]cyklooctadiene type are major constituents, a volatile oil with mono-
      and ses-quiterpens, an oil, organic acids and small amounts of additional
      compounds are also present. The content of major lignans (schizandrin,
      deoxyschizandrin, gomisin A, gomisin N, gamma-schizandrin, wuweizisu C) in
      commercially available drugs ranges usually between 3 and 5%. The present paper
      biefly comments the isolation and biological activity of the lignans and is
      especially concerned with analytical methods (TLC and HPLC) for the determination
      of the drug fingerprint and methods for the determination of constituents in
      drugs, mixtures and biological materials. HPLC methods using RP-silica bonded
      phases and diluted methanol, acetonitrile (or a mixture of both), are most
      important for these purposes. Electromigration methods are less suitable and the
      importance of hyphenation procedures is practically negligible.

PMID- 15556509
TI  - Determination of alpha-bisabolol in human blood by micro-HPLC-ion trap MS and
      head space-GC-MS methods.
AB  - Alpha-bisabolol is a compound present in some essential oils, widely distributed
      in several plants, including camomile. Two different methods for analysing an
      essential oil, such as alpha-bisabolol in human blood are reported: the first
      uses micro-liquid chromatography-electrospray ionisation-mass spectrometry
      (muHPLC-ESI-MS), whereas the second is based on "head space" injection coupled to
      gas chromatography-mass spectrometry (HS-GC-MS). For LC-ESI-MS, human blood
      samples, spiked with alpha-bisabolol, were extracted with hexane and evaporated
      to dryness under air stream. The residue was then reconstituted with methanol and
      injected into a C18 column, connected to an ion trap mass spectrometer equipped
      with an ESI source. Spectra were recorded in the positive ion, selected ion
      monitoring mode. The detection limit of alpha-bisabolol in blood was 0.125
      micromol/l. The preparation of samples for the analysis in HS-GC-MS was limited
      to blood dilution with water (0.5 ml blood + 1 ml water). Head space vials were
      heated at 125 degrees C for 1 h before automatic injection. The HS-GC-MS
      detection limit (0.13 micromol/l) was similar to that achieved with the muHPLC
      ESI-MS method. Successful tests were performed to verify if alpha-bisabolol could
      be directly measured by the HS-GC-MS method in different biological samples
      (blood, urine, faeces, homogenate tissues) from rats treated with the camomile
      essential oil.

PMID- 15556510
TI  - Analysis and retention behaviour in high-performance liquid chromatography of
      terpenic plant constituents (Sideritis spp.) with pharmacological interest.
AB  - Terpenoids are natural products with an important pharmacological interest, which
      are present in a number of medicinal plants. The species of Sideritis genus are
      valuable due to their high content in those compounds and they have been used in
      the Mediterranean area in folk medicine as anti-inflammatory and anti-ulcer
      agents. The present study describes a gradient elution reversed-phase method that
      uses diode array detection to determine ten pharmacologically active diterpenoids
      occurring in 12 species of Sideritis. First, we studied the chromatographic
      behaviour of standard diterpenoids to analyse the variation on retention time and
      the chromatographic properties with the mobile phase. Standard calibration curves
      were generated by plotting the area of peaks against a concentration range of the
      compounds. Second, the validated method was applied to the analyses of hexanic
      and methanolic extracts from 12 species of Sideritis, which were collected from
      different areas of Spain. Finally, we established for this plant a relationship
      between their use in folk medicine and their diterpenoid content.

PMID- 15556511
TI  - Current chemical tagging strategies for proteome analysis by mass spectrometry.
AB  - Proteomics, the analysis of the protein complement of a cell or an organism, has
      grown rapidly as a subdiscipline of the life sciences. Mass spectrometry (MS) is
      one of the central detection techniques in proteome analysis, yet it has to rely
      on prior sample preparation steps that reduce the enormous complexity of the
      protein mixtures obtained from biological systems. For that reason, a number of
      so-called tagging (or labeling) strategies have been developed that target
      specific amino acid residues or post-translational modifications, enabling the
      enrichment of subfractions via affinity clean-up, resulting in the identification
      of an ever increasing number of proteins. In addition, the attachment of stable
      isotope-labeled tags now allows the relative quantitation of protein levels of
      two samples, e.g. those representing different cell states, which is of great
      significance for drug discovery and molecular biology. Finally, tagging schemes
      also serve to facilitate interpretation of MS/MS spectra, therefore assisting in
      de novo elucidation of protein sequences and automated database searching. This
      review summarizes the different application fields for tagging strategies for
      today's MS-based proteome analysis. Advantages and drawbacks of the numerous
      strategies that have appeared in the literature in the last years are
      highlighted, and an outlook on emerging tagging techniques is given.

PMID- 15556512
TI  - Simultaneous determination of hypericin and hyperforin in human plasma with
      liquid chromatography-tandem mass spectrometry.
AB  - A selective and sensitive method for the simultaneous determination of hypericin
      and hyperforin--the two main active ingredients of St. John's Wort (SJW) extract-
      in human plasma depending on liquid/liquid-extraction and LC/MS/MS detection has
      been developed, validated after specifying the stability of the photosensitive
      hypericin in plasma samples during light exposure and applied to samples of a
      patient. After extraction with ethyl acetate/n-hexane in the darkness, sample
      extracts were chromatographed isocratically within 6 min on a Kromasil RP-18
      column. The analytes were detected with tandem mass spectrometry in the selected
      reaction monitoring mode using an electrospray ion source. The limit of
      quantification was 0.05 ng/mL for hypericin and 0.035 ng/mL for hyperforin. The
      accuracy of the method varied between 101.9 and 114.2% and the precision ranged
      from 4.7 to 15.4% (S.D., batch-to-batch) for both analytes. The method was linear
      at least between 0.05 and 10 ng/mL for hypericin and between 0.035 and 100 ng/mL
      for hyperforin. Using this method hypericin and hyperforin were determined
      successfully in a patient over seven days following discontinuation of exposure
      with therapeutic doses of St. John's Wort extract.

PMID- 15556513
TI  - Multiresidue confirmation of beta-agonists in bovine retina and liver using LC
      ES/MS/MS.
AB  - Misuse of numerous beta-agonist drugs for their growth promoting effects in
      livestock production requires significant regulatory enforcement activities
      worldwide. The proof of illegal drug use needed for regulatory action usually
      requires the high degree of specificity derived from mass spectrometric analysis
      of suspect tissues and body fluids. In this paper, we describe a multiresidue
      screening method for confirmation of nine beta-agonist compounds in bovine liver
      and retina. A wide range of analyte structures was selected in order to
      demonstrate applicability to other chemically related beta-agonists for which
      standards are not currently available. The class-specific method, which is based
      on mixed mode cation exchange/reverse phase solid phase extraction, reverse phase
      gradient LC separation using a cyanopropyl-silica phase, and tandem mass
      spectrometry (MS/MS) in the multiple reaction monitoring (MRM) mode, yields high
      analyte recoveries at the target level of 1 ppb (ng/g). In addition, acquisition
      of multiple MRM transitions for each analyte permits simultaneous confirmation of
      beta-agonists at the level of 1 ppb in liver and retina by using intensity ratios
      between fragment ions and protonated molecules. Estimated values for the limit of
      quantification (LOQ) for individual beta-agonists were 0.08-0.3 ppb in liver and
      0.02-0.5 in retina; the estimated limits of confirmation, using accepted criteria
      from international regulatory agencies, were 0.25-0.8 ppb in liver and 0.1-1 ppb
      in retina. This method should be useful in supporting regulatory enforcement
      programs that monitor beta-agonist misuse.

PMID- 15556514
TI  - Development of headspace solid-phase microextraction with on-fiber derivatization
      for determination of hexanal and heptanal in human blood.
AB  - Hexanal and heptanal in human blood have been regarded as potential biomarkers of
      lung cancer. Owing to their high volatilities and activities, it is difficult to
      accurately measure the two biomarkers. In the current work, headspace solid-phase
      microextraction (HS-SPME) with on-fiber derivatization technique was developed
      for quantitative analysis of hexanal and heptanal in human blood. In the proposed
      method, the two aldehydes in blood were headspace extracted by using a poly
      (dimethylsiloxane)/divinylbenzene (PDMS/DVB) fiber with O-2,3,4,5,6
      (pentafluorobenzyl) hydroxylamine (PFBHA) at 60 degrees C for 8 min. The aldehyde
      oximes formed on the fiber were desorbed and analyzed by gas chromatography-mass
      spectrometry (GC-MS). The method validations including detection limit, recovery
      and precision were studied. It was found that the method provided low detection
      limits of 0.006 nM for hexanal and 0.005 nM for heptanal, recoveries from 89% to
      95% and R.S.D. values less than 8.5%. The present method was applied to
      quantitative analysis of hexanal and heptanal in normal blood and lung cancer
      blood. Hexanal concentrations from 7.33 to 15.23 microM and heptanal
      concentrations from 2.47 to 9.23 microM were found in the lung cancer blood,
      while both hexanal and heptanal in the control blood were lower than 0.6 microM.
      This further demonstrated that hexanal and heptanal might be the biomarkers of
      lung cancer. The experimental results showed that GC-MS and HS-SPME with on-fiber
      derivatization is a simple, rapid, sensitive and solvent-free method for
      determination of in hexanal and heptanal human blood.

PMID- 15556515
TI  - Discrimination of Type 2 diabetic patients from healthy controls by using
      metabonomics method based on their serum fatty acid profiles.
AB  - Metabonomics, the study of metabolites and their roles in various disease states,
      is a novel methodology arising from the post-genomics era. This methodology has
      been applied in many fields, including work in cardiovascular research and drug
      toxicology. In this study, metabonomics method was employed to the diagnosis of
      Type 2 diabetes mellitus (DM2) based on serum lipid metabolites. The results
      suggested that serum fatty acid profiles determined by capillary gas
      chromatography combined with pattern recognition analysis of the data might
      provide an effective approach to the discrimination of Type 2 diabetic patients
      from healthy controls. And the applications of pattern recognition methods have
      improved the sensitivity and specificity greatly.

PMID- 15556516
TI  - Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive
      result from hepatitis and hepatocirrhosis diseases.
AB  - Metabonomics, the study of metabolites and their roles in various disease states,
      is a novel methodology arising from the post-genomics era. This methodology has
      been applied in many fields. Current metabonomics practice has relied on mass
      spectrometry (MS), gas chromatography-mass spectrometry (GC-MS), liquid
      chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) to
      analyze metabolites. In this study, a novel approach of using high-performance
      liquid chromatography (HPLC) in conjunction with developed software was employed.
      Using the principal components analysis method (PCA), all (113) peaks of urinary
      metabolites with a cis-diol structure from patients with hepatitis and
      hepatocirrhosis were compared to those from liver cancer patients. The results
      showed that the metabonomics-PCA method might be useful to differentiate between
      patients with hepatocirrhosis and hepatitis from patients with liver cancer while
      lowering false-positive rate. These findings also suggest that a subset of the
      urinary nucleosides identified with metabonomics correlate better with cancer
      diagnosis than the traditional single tumor marker alpha-fetoprotein (AFP).

PMID- 15556517
TI  - Experimental design as a tool when evaluating stationary phases for the capillary
      electrochromatographic separation of basic peptides.
AB  - Two different capillary electrochromatography (CEC) stationary phases, Hypersil
      phenyl and Hypersil C(18), have been characterised with respect to their ability
      to separate the four basic peptides H-Tyr-(D)Ala-Phe-Phe-NH(2) (TAPP), H-Tyr
      (D)Ala-Phe-NH(2) (TAP), H-Phe-Phe-NH(2) (PP) and H-Phe-NH(2) (P). Optimal
      separation conditions were first established separately for the two phases by
      applying experimental design in a stepwise procedure. The first step comprised a
      study to acquire basic knowledge about the variables, their influence on the
      response and their respective experimental domains for each of the two stationary
      phases. The second step was screening the significant variables and the third
      step was an optimisation with response surface modelling (RSM) to locate the
      optimum separation conditions for each stationary phase. The experimental
      procedure was identical for both stationary phases, but their respective
      experimental domains were different. The response functions were peak resolution
      and peak efficiency. This procedure enables specific optimal experimental
      conditions to be identified for each of the two stationary phases. The optimal
      conditions identified for the separation on the phenyl stationary phase were to
      use 50% ACN, 20% 50 mM Tris(hydroxymethyl)aminomethane (TRIS) pH 7.5, 30% H(2)O
      as BGE, operating at 20 degrees C and 20 kV high voltage. For the C(18)
      stationary phase optimal separation was achieved using a BGE with 80% ACN, 20% 30
      mM TRIS pH 8.5, again operating at 20 degrees C and 20 kV high voltage. Results
      show that the phenyl stationary phase is better suited for the separation of
      basic, hydrophilic peptides.

PMID- 15556518
TI  - Simultaneous determination of ebastine and its three metabolites in plasma using
      liquid chromatography-tandem mass spectrometry.
AB  - We developed a method for determining ebastine, a new generation of
      antihistamines, and its three metabolites (hydroxyebastine, carebastine and
      desalkylebastine) in plasma simultaneously using LC/MS/MS. Four compounds and
      terfenadine, an internal standard, were extracted from plasma using a mixture of
      diethylether and dichloromethane in the presence of 1 M HCl. After drying the
      organic layer, the residue was reconstituted in mobile phase (acetonitrile:5 mM
      ammonium acetate, 50:50, v/v) and injected onto a reversed-phase C(18) column.
      The isocratic mobile phase was eluted at 0.2 ml/min. The ion transitions
      monitored in multiple reaction-monitoring mode were m/z 470.7-->167.1, 486.7-
      >167.1, 500.6-->167.1, 268.4-->167.1 and 472.7-->436.0 for ebastine,
      hydroxyebastine, carebastine, desalkylebastine and terfenadine, respectively. The
      coefficient of variation of the assay precision was less than 12.5%, and the
      accuracy exceeded 88%. The limit of detection was 0.5 ng/ml for desalkylebastine;
      0.2 ng/ml for ebastine, hydroxyebastine and carebastine, respectively. This
      method was used to measure the plasma concentration of ebastine and its three
      metabolites from healthy subjects after a single 20 mg oral dose of ebastine.
      This analytic method is a very simple, sensitive, and accurate to determine the
      pharmacokinetic profiles of ebastine including its metabolites.

PMID- 15556519
TI  - Quantification of 5-azacytidine in plasma by electrospray tandem mass
      spectrometry coupled with high-performance liquid chromatography.
AB  - 5-Azacytidine (5AC), a nucleoside analogue and hypomethylating agent, has
      anticancer properties and has been utilized in the treatment of various
      malignancies. 5AC is unstable and rapidly hydrolyzed to several by-products,
      including 5-azacytosine and 5-azauracil. A sensitive, reliable method was
      developed to quantitate 5AC using LC/MS/MS to perform pharmacokinetic and
      pharmacodynamic studies on 5AC combination therapy trials. Blood samples were
      collected in a heparinized tube and immediately processed for storage. To
      increase the stability of 5AC in plasma, 25 ng/mL tetrahydrouridine was added to
      the plasma and snap frozen. Plasma samples were extracted using acetonitrile then
      cleaned up by Oasis MCX ion exchange solid-phase extraction cartridges. 5AC was
      separated on an YMC Jsphr M80 C(18) column with gradient elution of ammonium
      acetate (2 mM) with 0.1% formic acid and methanol mobile phase. 5AC elutes at 5.0
      +/- 0.2 min with a total run time of 30 min. Identification was through positive
      ion mode and multiple reaction monitoring mode at m/z+ 244.9-->113.0 for 5AC and
      m/z+ 242.0-->126.0 for 5-methyl-2'-deoxycytidine, the internal standard. The
      lower limit of quantitation of 5AC was 5 ng/mL in human plasma, and linearity was
      observed from 5 to 500 ng/mL fitted by linear regression with 1/x weight. This
      method is 50 times more sensitive than previously published assays and
      successfully allows studies to characterize the pharmacokinetics and
      pharmacodynamics of 5AC.

PMID- 15556520
TI  - Ultrasonic-assisted derivatization reaction of amino acids prior to their
      determination in urine by using single-drop microextraction in conjunction with
      gas chromatography.
AB  - A derivatization-extraction method that avoids tedious preconcentration steps is
      established in order to determine amino acids accurately at nanogram levels. The
      method involves conversion of the analytes of concern to N(O,S)-ethoxycarbonyl
      amino acid ethyl esters and subsequent extraction by single-drop microextraction
      (SDME) followed by GC analysis. The reaction proceeds smoothly and rapidly under
      ultrasonication which removes the bubbles from the bulk solution. Precision is
      acceptable and 12 non-hydrolyzed amino acids can be determined in urine in this
      manner. As long as the extraction conditions are consistently applied,
      quantitative analysis can be performed accurately. The limits of detection were
      satisfactory in the range 0.010-0.025 microg/ml for GC-FID and 0.26-68 ng/ml for
      GC-MS(SIM) with 1 ml sample volume.

PMID- 15556521
TI  - Determination of MK-0767 enantiomers in human plasma by normal phase LC-MS/MS.
AB  - A sensitive and selective analytical method for the enantioselective
      determination of MK-0767, a dual peroxisome proliferator-activated receptor
      (PPAR) alpha/gamma agonist, in human plasma has been developed and validated. The
      chromatography is based on normal-phase chiral separation on a Kromasil, 5
      microm, CHI-DMB 250 mm x 4.6 mm column. The detection involves the direct
      introduction of the normal phase eluent into MS/MS without the addition of a post
      column reagent. Atmospheric pressure chemical ionization (APcI) mode was selected
      as the ion source in this method. With proper sample handling and processing
      procedures, ex vivo interconversion of the enantiomers was kept to minimum during
      sample collection, preparation and short term storage of frozen human plasma
      samples. The method was successfully utilized to determine the concentrations of
      MK-0767 enantiomers in human plasma to support pharmacokinetic investigation in
      man.

PMID- 15556522
TI  - Quantification of residual EDU (N-ethyl-N'-(dimethylaminopropyl) carbodiimide
      (EDC) hydrolyzed urea derivative) and other residual by LC-MS/MS.
AB  - An LC-MS/MS method for determination of the break down product of N-ethyl-N'-(3
      dimethylaminopropyl) carbodiimide (EDC) urea derivative, EDU, has been developed
      and validated for monitoring the residual coupling reagents. Results indicate
      that the method exhibits suitable specificity, sensitivity, precision, linearity
      and accuracy for quantification of residual EDU in the presence of meningococcal
      polysaccharide-diphtheria toxoid conjugate vaccine and other vaccine matrix
      compounds. The assay has been validated for a detection range of 10-100 ng/mL and
      then successfully transferred to quality control (QC) lab. This same method has
      also been applied to the determination of residual diaminohexane (DAH) in the
      presence of EDU. LC-MS/MS has proven to be useful as a quick and sensitive
      approach for simultaneous determination of multiple residual compounds in
      glycoconjugate vaccine samples.

PMID- 15556523
TI  - Two step procedure for purification of enzymatically active prostate-specific
      antigen from seminal plasma.
AB  - The role of prostate-specific antigen (PSA) during the onset of prostate cancer
      and subsequent tumor growth and metastasis is not well understood. We have
      developed a simple two step procedure, based on principles of hydrophobic charge
      induction chromatography and molecular size chromatography to provide pure free
      PSA (f-PSA) preparation that is free from all other known PSA complexes as well
      as human kallikrein 2 (hK2). The overall recovery of f-PSA is 72%. The isolated f
      PSA consists of three known isoforms that corresponds to pI of 6.2, 6.4 and 7.2.
      f-PSA is enzymatically active and its enzymatic activity can be effectively
      neutralized by a serine protease inhibitor.

PMID- 15556524
TI  - Simultaneous determination of amoxicillin and clavulanic acid in human plasma by
      HPLC-ESI mass spectrometry.
AB  - A simple, fast and sensitive high-performance liquid chromatography (HPLC)-mass
      spectrometric (MS) method has been developed for simultaneous determination of
      amoxicillin and clavulanic acid in human plasma using terbutaline as internal
      standard. After precipitation of the plasma proteins with acetonitrile, the
      analytes were separated on a C(8) reversed-phase column with formic acid-water
      acetonirile (2:1000:100) and detected using electrospray ionization (ESI) mass
      spectrometry in negative selected ion monitoring (SIM) mode. The method was
      validated and successfully applied to analysis of amoxicillin and clavulanic acid
      in clinical studies. The limit of quantitation, 0.12 microg/ml for amoxicillin
      and 0.062 microg/ml for clavulanic acid, was five times lower than that of the
      published HPLC-UV method.

PMID- 15556525
TI  - New trends in sample preparation: on-line microextraction in packed syringe
      (MEPS) for LC and GC applications Part III: Determination and validation of local
      anaesthetics in human plasma samples using a cation-exchange sorbent, and MEPS-LC
      MS-MS.
AB  - The need for on-line sample preparation for high-throughput applications in
      bioanalysis has increased during the past decade. In this paper a robust and on
      line sample preparation technique, micro extraction in packed syringe (MEPS) has
      been developed and validated. The method is a miniaturized, fully automated,
      solid-phase extraction (SPE) technique that can be connected on-line to GC or LC
      without any modification of the chromatographs. The performance of MEPS as sample
      preparation method is illustrated by the determination of local anaesthetics in
      human plasma samples on-line with high performance liquid chromatography (HPLC)
      and tandem mass spectrometry. The sampling sorbent was 1mg silica based
      benzenesulphonic acid cation exchanger that was inserted in a 250 microl syringe.
      Ropicavine and two of its metabolites (PPX and 3-OH-ropivacine), lidocaine and
      bupivacine were used as model substances. The accuracy values of quality control
      samples (QC) were between 95% and 109%, and precision (relative standard
      deviation, R.S.D.) had a maximum deviation of 9% for the analytes.

PMID- 15556526
TI  - A new molecularly imprinted polymer for the selective extraction of naproxen from
      urine samples by solid-phase extraction.
AB  - A non-covalent molecularly imprinted polymer (MIP) was synthesised using naproxen
      (a non-steroidal, anti-inflammatory drug (NSAID)) as a template molecule. The MIP
      was chromatographically evaluated to confirm the imprinting effect, and was then
      applied as a selective sorbent in solid-phase extraction (SPE) to selectively
      extract naproxen. After this study, the MIP was used to extract naproxen from
      urine samples; it was demonstrated that by applying a selective washing step with
      acetonitrile (ACN) the compounds in the sample that were structurally related to
      naproxen could be eliminated.

PMID- 15556527
TI  - Determination of linezolid in plasma and bronchoalveolar lavage by high
      performance liquid chromatography with ultraviolet detection using a fully
      automated extraction method.
AB  - The aim of this study was to develop a specific and sensitive high-performance
      liquid chromatographic assay for the determination of linezolid in human plasma,
      and bronchoalveolar lavage. The sample extraction was based on a fully automated
      solid-phase extraction with an OASIS HLB cartridge. The method used ultraviolet
      detection set at a wavelength of 254 nm and a separation with a Zorbax Eclipse
      XDB C8 column. The assay has been found linear over the concentration range 0.02
      30 microg/ml and 0.04-30 microg/ml for linezolid, respectively, in plasma and
      bronchoalveolar lavage. It provided good validation data for accuracy and
      precision (CV <4.64% and 5.08%, accuracy in the range 96.93-102.67% and 97.33
      105.67%, respectively, for intra- and inter-day). The assay will be applied to
      determine the penetration of linezolid in human bronchoalveolar lavage during
      pharmacokinetic steady-state.

PMID- 15556528
TI  - Microwave-assisted derivatization of 2,5-hexanedione in urine: evaluation using
      GC-MS and GC-ECD.
AB  - 2,5-Hexanedione, the main metabolite of n-hexane, can be responsible for axonal
      degeneration symptoms via formation of pyrrol-adducts with several amino acids.
      In order to make it amenable to gas chromatographic analysis, a protocol
      including microwave assisted derivatization is presented and compared to state-of
      the-art technique of urine analysis. The applied methodology includes
      derivatization with O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine, extraction of
      the oximes and final analysis using either GC-MS or GC-muECD. Furthermore, the
      mass spectra of derivatized 2,5-hexanedione and 5-hydroxy-2-hexanone as well as
      preliminary excretion kinetics are provided. Orthogonal regression methodology
      demonstrated superior sensitivity for the microwave heating. Limits of detection
      were calculated to be approximately 20 ng mL(-1) with both MS and electron
      capture detection, the decompositon of excess derivatizing agent using sulfuric
      acid, following the reaction is beneficial. A matrix effect caused by urine was
      not observed, a calibration in aqueous matrix ensures accurate results therefore.
      Microwave heating yields excellent results regarding recovery, sensitivity and
      the time needed for sample preparation, furthermore, it is demonstrated that both
      mass selective as well as electron capture detection are of comparable
      suitability for this task.

PMID- 15556529
TI  - Variable recoveries of fatty acids following the separation of lipids on
      commercial silica gel TLC plates Selective loss of unsaturated fatty acids on
      certain brands of plates.
AB  - Since we recently noticed poor recoveries of unsaturated fatty acids (UFA) when
      the parent lipids were first separated on TLC plates, we investigated the source
      of this error by examining several variables, including the brand of TLC plate,
      nature of the lipid, and conditions of methylation. Of the five commercial brands
      of plates used, two (Baker and Whatman) showed loss of UFA, and three (Alltech
      Hardlayer, Alltech Softlayer, and Merck) did not. This loss occurred in both
      neutral and phospholipids, did not affect saturated acids, and was independent of
      the methylation reagent used. No loss occurred, however, if the lipids were
      eluted from the silica gel before methylation, indicating that the loss is due to
      oxidation of UFA in presence of certain brands of silica gel. These results show
      that some brands of TLC plates may be unsuitable for lipid analysis, if the aim
      is to determine the fatty acid composition by GC using direct methylation.

PMID- 15556530
TI  - High-performance liquid chromatographic total particles quantification of
      retroviral vectors pseudotyped with vesicular stomatitis virus-G glycoprotein.
AB  - A novel and rapid method for the total particles quantification of murine
      leukemia virus derived retroviral vectors pseudotyped with vesicular stomatitis
      virus-G glycoprotein was developed using high performance liquid chromatography.
      Virus particles were detected by absorbance at 260 nm and quantified using a
      calibration curve generated from highly purified and concentrated viral stock
      characterized by negative stain electron microscopy. The method requires
      Benzonase digestion and concentration of the supernatant prior to analysis. The
      virus eluted in 12.55 min at a flow rate of 1 mL/min in 20 mM Tris-Cl, pH 7.4 +
      1.1 M NaCl. The limits of detection and quantification of this assay were 4.71 x
      10(8) and 1.57 x 10(9) viral particles/mL, respectively. Linearity was between
      3.0 x 10(9) and 1.0 x 10(11) viral particles/mL with a correlation coefficient of
      0.9923 and a slope of 6 x 10(-6). The assay precision was <5% and <10% for intra-
      and inter-day analysis, respectively. This assay was used for the total particles
      quantification of a 7-day, large-scale perfusion culture production of a
      retroviral vector grown in 293 cells expressing the beta-galactosidase gene.

PMID- 15556531
TI  - Sensitive analytical method for Topiramate in human serum by HPLC with pre-column
      fluorescent derivatization and its application in human pharmacokinetic studies.
AB  - A sensitive and specific high performance liquid chromatographic method for
      quantitation of topiramate in human serum was developed using HPLC with
      fluorescence labeling reagent. Topiramate was extracted from human serum by
      dichloromethane and derivatized by reaction with 9-fluorenylmethyl chloroformate
      (FMOC-Cl) in the presence of borate buffer. Analysis was performed on a CN column
      with sodium phosphate buffer (pH 2.2) containing 1 ml/l triethylamine and
      methanol (52:48 (v/v)) as mobile phase. Amantadine was used as internal standard.
      The standard curve was linear over the range 20-5000 ng/ml of topiramate in human
      serum. The mean intra-day precision was from 10.5% (low concentration) to 1.2%
      (high concentration) and the within-day precision from 1.5 to 12.5% determined on
      spiked samples. The accuracy of the method was 96.5-107.5% (intra-day) and 98.4
      105% (inter-day). The limit of quantification was 20 ng/ml of serum. This method
      was used in a bioequivalence study after administration of 2 x 25 mg topiramate
      in 24 healthy volunteers.

PMID- 15556532
TI  - Efficient and sensitive detection of residues of nine coccidiostats in egg and
      muscle by liquid chromatography-electrospray tandem mass spectrometry.
AB  - We present a method based on electrospray liquid chromatography tandem mass
      spectrometry (LC-MS/MS) for determining in muscle and eggs the following nine
      coccidiostats: halofuginone, diclazuril, dinitrocarbanilide (the main metabolite
      of nicarbazin), robenidine, monensin, lasalocid, narasin, salinomycin, and
      maduramicin. Dinitrocarbanilide-d8, nigericin, and diclazuril-bis were used as
      internal standards. The method uses extraction in acetonitrile followed by a
      clean-up on an SiOH solid-phase extraction column. High-performance liquid
      chromatography (HPLC) separation was performed on a Purospher C(18) column (125
      mm x 3 mm i.d.) protected by a guard column, the mobile phase being a water
      acetonitrile gradient (each gradient component containing 0.1% formic acid) at a
      flow rate of 1 ml min(-1). For unequivocal identification of each analyte, two
      ions were detected and chosen for multiple reaction monitoring (MRM). Validation
      was carried out on spiked muscle and egg samples. The method described meets all
      the criteria of Decision 2002/657/EC and is easy to use in routine analysis.
      Validation results are presented with the measured CCalpha and CCbeta values.
      This whole method allows extraction and analysis of up to 24 samples per day.

PMID- 15556533
TI  - Comparison of performance of C18 monolithic rod columns and conventional C18
      particle-packed columns in liquid chromatographic determination of Estrogel and
      Ketoprofen gel.
AB  - The performance of monolithic HPLC columns Chromolith (made by Merck, Germany)
      and conventional C18 columns Discovery (Supelco, Sigma-Aldrich, Prague, Czech
      Republic) was tested and the comparison for two topical preparations Ketoprofen
      gel and Estrogel gel was made. The composition of mobile phases - for Ketoprofen
      analysis a mixture of acetonitrile, water and phosphate buffer adjusted to pH 3.5
      (40:58:2) and for Estrogel analysis a mixture of acetonitrile, methanol, water
      (23:24:53) - was usually not optimal for analyses at all types of columns. Thus
      an adjustment of components ratio was necessary for sufficient resolution of the
      compounds analysed. Various flow rates (1.0-5.0 ml/min) and mobile phases
      (usually increasing ratio of water content) were applied. Determination of active
      substances, preservatives and impurities and comparison of retention times and
      system suitability test parameters was accomplished. For Estrogel gel, following
      chromatographic conditions were found: using Chromolith Flash RP-18e monolith
      column, mobile phase was acetonitrile, methanol, water (13:24:63, v/v/v) and flow
      rate 3.0 ml/min. Using monolith column ChromolithSpeedROD RP-18e, the mobile
      phase was acetonitrile, methanol, water (18:24:58, v/v/v) and flow-rate 4.0
      ml/min. For the monolith column Chromolith Performance RP-18e, the mobile phase
      was acetonitrile, methanol, water (23:24:53, v/v/v), flow-rate 3.0ml/min.
      Analysis of Ketoprofen gel gave the best results using following analytical
      conditions: for monolith column Chromolith Flash RP-18e, mobile phase as a
      mixture of acetonitrile, water, phosphate buffer pH 3.5 (30:68:2, v/v/v) was
      used, at flow-rate 2.0 ml/min. For ChromolithSpeedROD RP-18e monolith column,
      acetonitrile, water, phosphate buffer pH 3.5 (35:63:2, v/v/v) was used as a
      mobile phase at flow-rate 3.0 ml/min. Chromolith Performance RP-18e gave the best
      results using mobile phase acetonitrile, water, phosphate buffer pH 3.5 (30:68:2,
      v/v/v) at the flow-rate 5.0 ml/min. It was proved that monolith columns, due to
      their porosity and low back-pressure, can save analysis time by about a factor of
      three with sufficient separation efficiency. Thus, for example 11 min long
      analysis can be performed in 4 min with comparable results.

PMID- 15556534
TI  - Determination of underivatised sterols and bile acid trimethyl silyl ether methyl
      esters by gas chromatography-mass spectrometry-single ion monitoring in faeces.
AB  - A method for quantification of total faecal sterols and bile acids (BAs) in human
      stool by using gas chromatography-mass spectrometry-single ion monitoring (GC-MS
      SIM) is described. Cholesterol, coprostanol, coprostanone, cholestanol, iso
      lithocholic acid (iso-LCA), lithocholic acid (LCA), iso-deoxycholic acid (iso
      DCA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), cholic acid (CA), and
      12-oxo-deoxycholic acid (12-oxo-DCA) in faeces of 86 healthy subjects were
      determined. The sample preparation for sterol analysis requires hydrolysis and
      liquid extraction from matrix, but no derivatisation. The GC-flame ionisation
      detection (FID) and total ion current (TIC) in GC-MS were not sufficient for
      sterol and BA determination, whereas selectivity and specificity of the GC-MS-SIM
      ensured the analysis of sterols and BAs in faeces.

PMID- 15556535
TI  - Simultaneous determination of the antiretroviral agents: amprenavir, lopinavir,
      ritonavir, saquinavir and efavirenz in human peripheral blood mononuclear cells
      by high-performance liquid chromatography-mass spectrometry.
AB  - A selective and accurate assay for the simultaneous quantitation of four protease
      inhibitors (PIs) (amprenavir (APV), lopinavir (LPV), ritonavir (RTV) and
      saquinavir (SQV)) and a non-nucleoside reverse transcriptase inhibitor (NNRTI)
      (efavirenz, EFV) in human peripheral blood mononuclear cells using high
      performance liquid chromatography-mass chromatography (LC/MS) has been developed
      and validated. After liquid-liquid extraction, the antiretroviral agents were
      separated within 15 min. The calibration curves of each drug showed a good
      linearity in a range of concentration between 2 and 200 ng/3 x 10(6) cells for
      amprenavir, lopinavir, efavirenz, 1.60 and 128 ng/3 x 10(6) cells for ritonavir
      and saquinavir. Mean intra- and inter-assay coefficients of variation over the
      ranges of the standard curves were less than 15% and mean extraction recoveries
      ranged 88.7-112.1%. The limits of quantification were 2 ng/3 x 10(6) cells for
      amprenavir, lopinavir, efavirenz, 1 ng/3 x 10(6) cells for ritonavir and 1.6 ng/3
      x 10(6) cells for saquinavir. This novel LC/MS assay, which provides an excellent
      method for simultaneous intra-cellular determination of amprenavir, lopinavir,
      ritonavir, saquinavir and efavirenz in human peripheral blood mononuclear cells,
      could be successfully applied for therapeutic drug monitoring and pharmacokinetic
      studies.

PMID- 15556536
TI  - LC-MS/MS analysis of dextromethorphan metabolism in human saliva and urine to
      determine CYP2D6 phenotype and individual variability in N-demethylation and
      glucuronidation.
AB  - In order to establish a fast screening method for the determination of the CYP2D6
      metabolic phenotype a sensitive LC-MS/MS assay to quantify dextromethorphan (DEX)
      and its O-demethylated metabolite dextrorphan (DOR) in human saliva was developed
      with limits of quantitation of 1 pmol/ml. Saliva was provided by 170 medical
      students 2h after oral ingestion of 30 mg (81 micromol) dextromethorphan
      hydrobromide. Individual ratios of the concentrations DEX/DOR (metabolic ratio,
      MR(DEX/DOR)) varied more than 25,000-fold (0.03-780). Two groups comprising 156
      'Extensive' and 14 'Poor Metabolizers' were clearly distinguished. For the
      investigation of individual differences in N-demethylation and glucuronidation,
      four additional metabolites of DEX, 3-methoxymorphinan (MOM), 3-hydroxymorphinan
      (HOM), and the two O-glucuronides (DORGlu and HOMGlu) were measured by LC-MS/MS
      analysis of 6-h urine of 24 volunteers. The N-demethylation reactions DEX-to-MOM
      and DOR-to-HOM defined by the respective MR were significantly correlated. The
      same holds for the glucuronidation pathways (MR(DOR/DORGlu) versus
      MR(HOM/HOMGlu)). The three poor CYP2D6 metabolizers excreted relatively high
      amounts of the parent compound DEX (up to 7 micromol), but only low amounts of
      glucuronides (DORGlu: 0.4-1.0 micromol; HOMGlu: 0.2-0.7 micromol). For the 21
      'Extensive Metabolizers', the two glucuronides were the most abundant, with
      relatively little interindividual variation (DORGlu: 10-44 micromol; HOMGlu: 5-17
      micromol). For the excretion of the glucuronides, two normal distributions
      provided the best fit, indicating that the determination of the glucuronides
      alone could allow assignment of the CYP2D6 metabolic phenotype.

PMID- 15556537
TI  - Quantification of zolmitriptan in plasma by high-performance liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - A sensitive and specific liquid chromatography electrospray ionization mass
      spectrometry (LC-ESI-MS) method has been developed and validated for the
      identification and quantification of zolmitriptan in human plasma. After the
      addition of the internal standard (IS) and 1.0 M sodium hydroxide solution,
      plasma samples were extracted with methylene chloride:ethyl acetate mixture
      (20:80, v/v). The organic layer was evaporated under a stream of nitrogen at 40
      degrees C. The residue was reconstituted with 100 microl mobile phase. The
      compounds were separated on a prepacked Lichrospher CN (5 microm, 150 mm x 2.0
      mm) column using a mixture of methanol:water (10 mM NH(4)AC, pH 4.0) = 78:22 as
      mobile phase. Detection was performed on a single quadrupole mass spectrometer by
      selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The
      method was proved to be sensitive and specific by testing six different plasma
      batches. Linearity was established for the range of concentrations 0.30-16.0
      ng/ml with a coefficient of determination (r) of 0.9998 and good back-calculated
      accuracy and precision. The intra- and inter-day precision (R.S.D.%) were lower
      than 15% and accuracy ranged from 85 to 115%. The lower limit of quantification
      was identifiable and reproducible at 0.30 ng/ml. The proposed method enables the
      unambiguous identification and quantification of zolmitriptan for
      pharmacokinetic, bioavailability or bioequivalence studies.

PMID- 15556538
TI  - On-line screening of conformationally constrained nicotines and anabasines for
      agonist activity at the alpha3beta4- and alpha4beta2-nicotinic acetylcholine
      receptors using immobilized receptor-based liquid chromatographic stationary
      phases.
AB  - Liquid chromatography columns containing stationary phases based upon immobilized
      nicotinic acetylcholine receptors (nAChRs) were used to screen a series of
      conformationally constrained nicotine and anabasine derivatives for agonist
      activity. The alpha3beta4 nAChR and alpha4beta2 nAChR subtypes were used to
      prepare the chromatographic columns and [(3)H] epibatidine dihydrochloride
      ([(3)H] EB) was used as the marker ligand. Single displacement experiments were
      conducted with the test ligands and with nicotine and carbachol. Nicotine was
      used as an internal control for compounds with agonist activity and carbachol was
      used as an internal control for compounds with very weak agonistic activity (K(d)
      > 4700 nM for alpha3beta4). The displacement of [(3)H] EB by each of the test
      compounds and internal controls was calculated and expressed as Deltaml.
      Functional studies were then conducted using a stably transfected cell line that
      expresses the alpha3beta4 nAChR and EC(50) values were determined for the test
      compounds and the internal controls. A comparison of the Deltaml and EC(50)
      values indicated that 9/11 compounds had been correctly identified as agonists or
      non-agonists of the alpha3beta4 nAChR. A similar comparison could not be made for
      the alpha4beta2 nAChR, since the intact cell line was not available for testing.
      The results of the study suggest that the immobilized nAChR columns can be used
      for the rapid on-line screening of compounds for their relative affinities for
      the immobilized receptor and as an initial determination of qualitative
      functional activities.

PMID- 15556539
TI  - Direct detection of boldenone sulfate and glucuronide conjugates in horse urine
      by ion trap liquid chromatography-mass spectrometry.
AB  - A study of the equine phase II metabolism of the anabolic agent boldenone is
      reported. Boldenone sulfate, boldenone glucuronide and their C17-epimers were
      synthesised as reference standards in our lab and a method was developed for
      their detection in a horse urine matrix. Solid phase extraction was used to
      purify the analytes, which were then detected by ion trap LC/MS. Negative and
      positive ionisation mode MS(2) were used for the detection of sulfate and
      glucuronide conjugates, respectively. Boldenone sulfate and 17-epiboldenone
      glucuronide were detected as the major and minor phase II metabolites,
      respectively, in horse urine samples collected following the administration of
      boldenone undecylenate by intramuscular injection.

PMID- 15556540
TI  - Direct injection, column switching-liquid chromatographic technique for the
      estimation of rabeprazole in bioequivalence study.
AB  - A rapid, simple and sensitive high-performance liquid chromatography-ultra violet
      (HPLC-UV) method with column switching between sample pre-treatment column and
      analytical column was developed for the quantitation of rabeprazole in human
      plasma; on a Bio-Sample Analysis system (Co-sense for BA) from Shimadzu
      Corporation, Kyoto, Japan. Zaleplon was used as an internal standard. The method
      was validated as per USFDA guidelines for the concentration range of 20.0-1200.0
      ng/mL and the correlation coefficient were found to be better than 0.999.
      Recovery of rabeprazole as well as the internal standard from human plasma was
      more than 90.0%. Rabeprazole was stable in human plasma for 4 months at -70 +/- 5
      degrees C and for 20.0 h at ambient temperature. In the auto sampler, the drug
      was stable for 24.0 h at 4 degrees C. The method was specific as there were no
      interfering peaks in the human plasma eluting at the retention times of the
      rabeprazole and the internal standard. The frozen plasma samples containing
      rabeprazole were stable to three freeze thaw cycles. The bioanalytical method was
      rugged in terms of inter- and intra-day accuracy and precision. The method was
      simple, specific, sensitive, precise, accurate and suitable for bioequivalence
      and pharmacokinetic studies. It was successfully applied to the pilot
      bioequivalence study of 20mg rabeprazole tablet of German Remedies Ltd. (A
      division of Cadila Healthcare Ltd.), India versus Pariet tablet of Eisai Ltd. &
      Janssen-Cilag Ltd., Japan in male human subjects.

PMID- 15556541
TI  - Improved detection limit for a direct determination of 8-hydroxy-2'
      deoxyguanosine in untreated urine samples by capillary electrophoresis with
      optical detection.
AB  - Method for a direct determination of 8-hydroxy-2'-deoxyguanosine (8OHdG) in
      untreated urine samples by capillary electrophoresis with optical detection was
      developed. Optimisation of conditions resulted in a significant lowering of the
      limit of detection (LOD) by a factor of 400 as compared to our previous study.
      Optimum separation of 8OHdG from other urine components was achieved using the
      separation electrolyte containing 80 mM 2-(cyclohexylamino)ethanesulfonic acid, 9
      mM LiOH (pH 8.6), and 0.1 mM cetyltrimethylammonium bromide ensuring the electro
      osmotic flow inversion. In the model aqueous samples, these conditions allow
      separating 8OHdG and 2'-deoxyguanosine (dG) from other nucleosides/nucleotides
      including 2'-deoxycitidine 5'-monophosphate (dCMP), thymidine 5'-monophosphate
      (TMP), adenosine (A), and thymidine (T). On the other hand, 2'-deoxyadenosine 5'
      monophosphate (dAMP) and 2'-deoxyguanosine 5'-monophosphate (dGMP) migrate
      together, and guanosine (G), 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC) are
      transported as neutral species with the electro-osmotic flow. In the spiked urine
      samples, 8OHdG and dG are well separated from each other and from other urine
      components and exhibit a linear calibration over the concentration range of 0.1
      2.0 microM for 8OHdG (LOD = 42 nM) and 0.2-5.0 microM for dG (LOD = 86 nM), but
      urine metabolites interfere with the determination of dCMP, TMP, A and T. Method
      is applicable to untreated urine samples with slightly enhanced levels of 8OHdG
      compared to that found in healthy individuals.

PMID- 15556542
TI  - Liquid chromatography-mass spectrometry method for determination of
      tetramethylpyrazine and its metabolite in dog plasma.
AB  - A liquid chromatography-mass spectrometry method is described for the
      determination of tetramethylpyrazine (TMP) and its active metabolite, 2
      hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) in dog plasma. This method involves
      a plasma clean-up step using protein precipitation procedure followed by LC
      separation and positive electrospray ionization mass spectrometry detection (ESI
      MS). Chromatographic separation of the analytes was achieved on a C18 column
      using a mobile phase of methanol, water and acetic acid (50:50:0.6, v/v/v) at a
      flow rate of 1.0 ml/min. Selected ion monitoring (SIM) mode was used for analyte
      quantitation at m/z 137.2 for TMP, m/z 153.2 for HTMP and m/z 195.2 for caffeine.
      The linearity was obtained over the concentration ranges of 20-6000 ng/ml for TMP
      and 20-4000 ng/ml for HTMP and the lower limit of quantitation was 20 ng/ml for
      both analytes. For each level of QC samples, both inter- and intra-day precisions
      (R.S.D.) were <or=7.4% for TMP and <or=6.0% for HTMP, and accuracy (R.E.) was +/
      6.0% for TMP and <or=3.5% for HTMP. The proposed LC-MS method was successfully
      applied to the pharmacokinetic studies of a TMP formulation preparation after
      oral administration to beagle dogs.

PMID- 15556543
TI  - Evaluation of four capillary columns for the analysis of organochlorine
      pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers in
      human serum for epidemiologic studies.
AB  - The separation of organochlorine pesticides (OCPs), polychlorinated biphenyls
      (PCBs), and polybrominated diphenyl ether (PBDE) congeners was evaluated on four
      capillary columns: 60 m x 0.25 mm i.d., 0.25 microm film thickness RTX-5MS and DB
      XLB capillary columns, and 60 m x 0.18 mm i.d., 0.25 microm film thickness DB-XLB
      and DB-5MS capillary columns. Based on performance, capacity, and cost, the RTX
      5MS (60 m x 0.25 mm i.d., 0.25 microm thickness) and the DB-XLB (60 m x 0.25 mm
      i.d., 0.25 microm film thickness) were selected for the analysis of human serum
      extracts by using gas chromatography/electron-capture detection. In contrast to
      previous studies, the oven temperature program affords the separation of
      congeners that are not separated by using other combinations of capillary
      columns, most notably PBDE-47 and PCB 180. In addition, the method enables
      determination of OCPs, PCBs, and PBDEs prevalent in a single extract of serum,
      which can lead to considerable time savings in the analysis of large number of
      samples collected for epidemiologic studies.

PMID- 15556544
TI  - Determination of total mycophenolic acid and its glucuronide metabolite using
      liquid chromatography with ultraviolet detection and unbound mycophenolic acid
      using tandem mass spectrometry.
AB  - Two simple, sensitive and reproducible methods for determination of total
      mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) as well as unbound
      MPA (fMPA) was developed by the use of HPLC-UV and LC-MS/MS methods,
      respectively. For the total MPA/MPAG method, the analytes were extracted using
      Isolute C(2) solid-phase extraction (SPE) cartridges and analyzed at 254 nm over
      a Zorbax Rx C(8) column (150 mm x 4.6 mm, 5 microm). The mobile phase was a
      gradient mixture of methanol and water (containing 0.1% (v/v) phosphoric acid).
      The total run time was 18 min and the extraction recovery was 77% for MPA and 84%
      for MPAG. The method was precise and accurate with a lower limit of
      quantification (LLOQ) of 0.5 mg/l for MPA and 5.0 mg/l for MPAG. For the fMPA
      method, plasma was subjected to ultrafiltration followed by SPE using C(18)
      cartridges. Analytical column was the same as the HPLC-UV method and the mobile
      phase was a gradient composition of methanol:0.05% formic acid with a flow rate
      of 0.6 ml/min for the first 3 min and 0.7 ml for the last 4 min. The
      chromatographic method separated MPA from its metabolites MPAG and Acyl-MPAG.
      Mass transitions in negative ionization mode for MPA and the internal standard,
      indomethacin were m/z: 319-->190.9 and m/z: 356-->312.2, respectively. The assay
      was linear in the concentration range of 1-1000 microg/l for fMPA with a LLOQ of
      1 microg/l and an accuracy of >95%. The two methods reported have an adequate
      degree of robustness and dynamic concentration range for the measurement of MPA,
      MPAG and fMPA for therapeutic drug monitoring purposes or pharmacokinetics
      investigations.

PMID- 15556545
TI  - Rodenticide-humic acid adsorption mechanisms and role of humic acid on their
      toxicity on human keratinocytes: chromatographic approach to support the
      biological data.
AB  - Humic substances are the most important soil components affecting the behaviour
      and performances of herbicides in the soil-water-organism system. In this paper,
      a chromatographic approach was used for analysis of anticoagulant rodenticide
      humic acid adsorption mechanisms. Using an equilibrium perturbation method, it
      was clearly shown that: (i) humic acid can be adsorbed on the C18 stationary
      phase, and (ii) all the rodenticides can be adsorbed on the humic acid adsorbed
      on the C18 stationary phase. This approach allowed the determination of the
      adsorption constant values between the anticoagulant rodenticides and humic acid
      as well as the corresponding thermodynamic data of this adsorption mechanism. The
      role of humic acid on the toxicity of these rodenticides on human keratinocytes
      was also clearly described in relation to these physico-chemical data.

PMID- 15556546
TI  - Urinary excretion of lignans after administration of isolated plant lignans to
      rats: the effect of single dose and ten-day exposures.
AB  - The difference in urinary excretion of mammalian and plant lignans in rats was
      determined after oral administration of equivalent doses (25 mg/kg of body
      weight) of 7-hydroxymatairesinol (HMR), lariciresinol (LAR), matairesinol (MR),
      and secoisolariciresinol (SECO). Twenty-four hours-urine samples were collected
      after a single dose and after administration of one dose/day for 10 days. Eight
      lignans were analysed in urine extracts using a high-performance liquid
      chromatography-tandem mass spectrometry method showing good sensitivity and
      repeatability. After a single dose of HMR, LAR, MR, and SECO, the main
      metabolites were 7-hydroxyenterolactone (HENL), cyclolariciresinol (CLAR),
      enterolactone (ENL), and enterodiol (END), respectively, but after 10-day
      exposure ENL was the main metabolite of all the tested lignans, showing a
      considerably higher excretion than after a single dose. Metabolic transformations
      of plant lignans into each other could also be observed.

PMID- 15556547
TI  - Determination of 8:2 fluorotelomer alcohol in animal plasma and tissues by gas
      chromatography-mass spectrometry.
AB  - Fluorotelomer alcohols (FTOHs) constitute an important group of compounds among
      the perfluoroalkyl substances (PFAS). The PFAS have recently been a focus of many
      environmental and biological studies. This generated a strong need for analytical
      methods for analysis of PFAS at trace levels in various environmental and
      biological matrices. A quantitative analytical method for analysis of 8:2 FTOH in
      rat plasma and rat liver, kidney, and adipose tissue using GC-MS with electron
      impact (EI) ionization was developed and validated. Extraction of water-diluted
      plasma with methyl tert-butyl ether (MTBE) was used for rat plasma. The analysis
      of rat liver or kidney tissues required homogenization of tissue on ice,
      extraction with hexane, and clean up of the extract by silica (Si) normal-phase
      solid phase extraction (SPE). Similarly, the adipose tissue was dissolved in n
      heptane and cleaned up by Si SPE. The methods were validated by performing spike
      recovery experiments for each type of matrix investigated and tested on authentic
      samples originating from 8:2 FTOH toxicological studies.

PMID- 15556548
TI  - Screening and semi-quantitative analysis of post mortem blood for basic drugs
      using gas chromatography/ion trap mass spectrometry.
AB  - The study presented here shows that GC-MS with ion trap detection can be used for
      screening post mortem blood. The method described was used to simultaneously
      screen for unknowns, identify basic drugs present and semi-quantitate 14 drugs
      commonly encountered in coroner's toxicology (i.e. was used to determine whether
      the drugs were present in sub-therapeutic, therapeutic or greater than
      therapeutic amounts). The equipment used included a Varian Saturn 2000 GC-MS
      operating in full scan mode, a CP-3800 GC, a CP-8400 autosampler and Saturn GC-MS
      workstation Version 5.5 software. Post mortem blood samples were extracted using
      a standard liquid-liquid procedure; diethylether followed by back extraction into
      0.1 M HCl. Standard curves for the 14 drugs which were semi-quantitated
      (amitriptyline, citalopram, clozapine, cocaine, cyclizine, diazepam,
      dihydrocodeine, dothiepin, methadone, mirtazapine, procyclidine, sertraline,
      tramadol, venlafaxine) were prepared covering the concentration range 0-1.0
      ug/mL. The procedure is in routine use for coroners toxicology; semi-quantitation
      has been used (i) to speed-up the through put of cases where drugs are an
      incidental finding and (ii) for cases where the amount of sample submitted for
      analysis was too small to allow for screening, identification and quantitation on
      separate sample volumes.

PMID- 15556549
TI  - Selective and sensitive liquid chromatography-tandem mass spectrometry method for
      the determination of levonorgestrel in human plasma.
AB  - A selective, sensitive and rapid liquid chromatography-tandem mass spectrometry
      method for the determination of levonorgestrel in plasma was developed. An
      Applied Biosystems API 3000 triple quadrupole mass spectrometer set to multiple
      reaction monitoring (MRM) mode, using atmospheric pressure photospray ionisation
      (APPI) in the positive mode. Using 17-alpha-methyltestosterone as internal
      standard (IS), liquid-liquid extraction was followed by reversed phase liquid
      chromatography using a phenyl-hexyl column and tandem mass spectrometric
      detection. The mean recovery for levonorgestrel and 17-alpha-methyltestosterone
      was 99.5 and 62.9%, respectively. The method was validated from 0.265 to 130 ng
      levonorgestrel/ml plasma with the lower limit of quantification (LLOQ) set at
      0.265 ng/ml. This assay method makes use of the increased sensitivity and
      selectivity of tandem mass spectrometric (MS/MS) detection, allowing for a rapid
      (extraction and chromatography) and selective method for the determination of
      levonorgestrel in human plasma. The assay method was used in a pharmacokinetic
      study to quantify levonorgestrel in human plasma samples generated after
      administrating a single oral dose of 1.5 mg levonorgestrel to healthy female
      volunteers for up to five half lives. The total chromatographic runtime of this
      method was 5.0 min per sample, allowing for analysis of a large number of samples
      per batch.

PMID- 15556550
TI  - Simultaneous determination of enalapril and enalaprilat in human plasma by liquid
      chromatography-tandem mass spectrometry.
AB  - A rapid, sensitive, and highly selective liquid chromatography-tandem mass
      spectrometry method was developed and validated for simultaneous determination of
      enalapril and its major active metabolite enalaprilat in human plasma. The
      analytes were extracted from plasma samples by liquid-liquid extraction,
      separated on a Zorbax Extend-C(18) column, and detected by tandem mass
      spectrometry with a Turbo IonSpray ionization interface. The method has a lower
      limit of quantification (LLOQ) of 0.1 ng/ml for both enalapril and enalaprilat.
      The chromatographic run time was approximately 3.5 min. The standard calibration
      curves for both enalapril and enalaprilat were linear in the concentration ranges
      of 0.10-100.0 ng/ml in human plasma. The intra- and inter-run precisions,
      expressed as the relative standard deviation (R.S.D.), were less than 7.7 and
      7.8%, determined from QC samples for enalapril and enalaprilat, and accuracy was
      within +/-3.9 and +/-2.7% in terms of relative error, respectively. The method
      was successfully applied for the evaluation of the pharmacokinetics of enalapril
      and enalaprilat in 20 volunteers after an oral dose of 10 mg enalapril maleate.

PMID- 15556551
TI  - Enantioselective pharmacokinetics of lercanidipine in healthy volunteers.
AB  - OBJECTIVE: The enantioselective kinetic disposition of lercanidipine, a
      dihydropyridine type of third-generation calcium antagonist, was investigated in
      six healthy male volunteers following a single 20 mg racemic oral dose. METHODS:
      Serial plasma samples were obtained from 0 to 24 h after drug administration.
      Lercanidipine enantiomers were analysed using a chiral LC-MS-MS method. RESULTS:
      The following differences (p < 0.05, Wilcoxon test) between (S) and (R)
      enantiomers were found (median): C(max) 2.071 ng mL(-1) versus 1.681 ng mL(-1);
      AUC(0-24)12.352 ng h mL(-1) versus 10.063 ng h mL(-1) and Cl/f 732.16 L h(-1)
      versus 1891.84 L h(-1). The AUC(0-infinity) values for (S)-LER were 1.21-fold
      higher than those for (R)-LER. CONCLUSION: The pharmacokinetics of LER was
      enantioselective in healthy volunteers following a single dose of 20 mg of the
      unlabeled racemic drug.

PMID- 15556552
TI  - Simultaneous determination of digoxin and permeability markers in rat in situ
      intestinal perfusion samples by RP-HPLC.
AB  - A simple, sensitive and specific reversed-phase high performance liquid
      chromatographic (RP-HPLC) assay for simultaneous determination of digoxin and
      permeability markers, in samples obtained from intestinal in situ single-pass
      perfusion studies, was developed and validated. Chromatography was carried on C
      18 column with mobile phase comprising of acetate buffer (pH 3.0), acetonitrile
      and methanol in the ratio of 50:25:25 (v/v/v), was pumped at a flow rate of 0.5
      ml/min and UV detection was employed at 220 nm. The average retention times for
      phenolred, propranolol, frusemide and digoxin were 9.1, 10.7, 12.9 and 15.3 min,
      respectively. The calibration curves were linear (R(2) > 0.998) in the range for
      each analyte. The method is specific and sensitive with limit of quantification
      of 25 ng/ml for digoxin and frusemide and 10 ng/ml for phenolred and propranolol.
      The method is accurate and precise with recoveries of digoxin in the range of
      95.2 and 103.2% and relative standard deviation (R.S.D.) <5%. We found that this
      method was simple and reliable in permeability determination and to estimate the
      contribution of P-glycoprotein in limiting intestinal absorption.

PMID- 15556553
TI  - Determination of atazanavir and other antiretroviral drugs (indinavir,
      amprenavir, nelfinavir and its active metabolite M8, saquinavir, ritonavir,
      lopinavir, nevirapine and efavirenz) plasma levels by high performance liquid
      chromatography with UV detection.
AB  - A global method is proposed for therapeutic drug monitoring of atazanavir, a
      novel protease inhibitor and of all other protease inhibitors (PI) and non
      nucleoside reverse transcriptase inhibitors (NNRTI) which are currently used to
      treat HIV patients. All drugs are extracted after a liquid-liquid extraction and
      separated on a C18 column with a binary gradient elution except lopinavir which
      is separated without this gradient. The absorbance is measured at 259 nm except
      for lopinavir (205 nm) and nevirapine (320 nm). This method is specific,
      accurate, precise (the intra-day and inter-day imprecision and inaccuracy are
      lower than 15%) and the limits of quantitation (0.40 mg/L for nevirapine, 0.10
      mg/L for indinavir, 0.10 mg/l for M8, 0.05 mg/L for amprenavir, 0.10 mg/L for
      nelfinavir, 0.10 mg/L for saquinavir, 0.10 mg/L for ritonavir, 0.10 mg/L for
      efavirenz, 0.10 mg/L for atazanavir and 0.20 mg/L for lopinavir) are consistent
      with trough plasma concentrations allowing to use this method for therapeutic
      drug monitoring of PI and NNRTI.

PMID- 15556554
TI  - Assessment of nitric oxide biosynthesis and peroxynitrite formation within the
      central nervous system by measuring L-citrulline in the cerebrospinal fluid?

PMID- 15556555
TI  - Monitoring aromatic hydrocarbons by whole cell electrochemical biosensors.
AB  - In this article, we describe a bacterial whole cell electrochemical biosensors
      system that can be used for monitoring aromatic hydrocarbons. These bacterial
      biosensors are based on fusions of a promoter that is sensitive to aromatic
      compounds (the promoter region of the xylS gene and the xylR gene coding for the
      transcriptional regulator of the xyl operon) to reporter genes that can be
      monitored electrochemically at real-time and on-line. The xylS promoter was fused
      upstream of two promoterless genes coding the lacZ gene and phoA. These
      constructs reacted specifically to aromatic compounds but not to nonaromatic
      compounds, and we could detect, within minutes, micromolar concentrations of
      different aromatic hydrocarbons such as xylene and toluene. The use of two
      different reporter genes allows the future construction of a multianalyte
      detection system for simultaneous monitoring of several pollutants. These whole
      cell biosensors are potentially useful for on-line and in situ detection of
      aromatic compounds and as early warning systems of environmental hazards.

PMID- 15556556
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      based amino acid analysis.
AB  - Amino acid analysis has been an integral part of analytical biochemistry for more
      than 50 years. However, its experimental design, which includes derivatization of
      amino acids followed by some kind of chromatographic separation, has not changed
      over the years. We have developed a matrix-assisted laser desorption/ionization
      time-of-flight (MALDI-TOF)-based method for the quantitative analysis of amino
      acids. This method does not require any amino acid modification, derivatization,
      or chromatographic separation. The data acquisition time is decreased to several
      seconds for a single sample. No significant ion suppression effects were observed
      with the developed sample deposition technique, and the method was found to be
      reproducible. Linear responses between the amino acid concentration and the peak
      intensities ratio of corresponding amino acid to internal standard were observed
      for all amino acids analyzed in the range of concentrations from 20 to 300
      microM, and correlation coefficients were between 0.983 (for arginine) and 0.999
      (for phenylalanine). Limits of quantitation were between 0.03 microM (for
      arginine) and 3.7 microM (for histidine and homocysteine). This method was
      applicable to the mixtures of free amino acids as well as to HCl hydrolysates of
      proteins. Furthermore, we have shown that this method can be applied to other
      biologically important low-molecular weight compounds such as glucose.

PMID- 15556557
TI  - A method for coupled transcription and aminoacylation of cysteinyl-tRNA.
AB  - A novel method for coupled transcription and aminoacylation of transfer RNA was
      developed where Escherichia coli cysteine-specific tRNA (tRNA(cys)) was
      transcribed and aminoacylated in a single reaction. The cys-tRNA(cys) that was
      synthesized and aminoacylated using this method was functional in in vitro
      translation. The cys-tRNA(cys) was further modified with biotin (N-iodoacetyl-N
      biotinhexylenediamine) to facilitate detection. The biotin-modified cys
      tRNAs(cys) was also functional in in vitro translation, allowing the synthesis
      and detection of biotin-labeled protein.

PMID- 15556558
TI  - Fluorescein conjugates of 9- and 10-hydroxystearic acids: synthetic strategies,
      photophysical characterization, and confocal microscopy applications.
AB  - Different strategies are presented to conjugate a fluorescein moiety to 9- and 10
      hydroxystearic acids (HSAs). 5-Amino-fluorescein (5-AF) was used as a starting
      reagent. When reacted with acyl-chloride-modified HSAs, 5-AF gave rise to stable
      amide derivatives with a 75% reaction yield. These products exhibited the typical
      steady-state and time-resolved fluorescence properties of the fluorescein
      chromophore with absorption at 494 nm and emission at 519 nm. Flow cytometry
      studies confirmed the distinct proapoptotic effect of underivatized 9-HSA on
      Jurkat cells and revealed a comparable ability of its amide derivative. Confocal
      microscopy imaging studies showed that green fluorescence could stain
      intracellular membranous structures. Moreover, dual-dye labeling with Mito
      Tracker Red, followed by colocalization analysis, revealed that HSA can move to
      the mitochondria. Thus, fluorescent derivatives of HSA can be used to monitor the
      localization of these biologically active molecules in living cells and can
      provide a useful tool for linking biochemical investigation with optical
      visualization methods. In contrast, when unmodified HSAs were used, the reaction
      gave monoesterified and diesterified fluorescein derivatives. These products
      exhibited unusual steady-state and time-resolved fluorescence properties with the
      excitation wavelength at 342 nm and the emission wavelength at 432 nm. It is
      shown that the synthesized HSA amides of fluorescein provide all of the typical
      photophysical and instrumental advantages of this popular dye, whereas the
      unusual luminescence and excitation properties of the monoester and diester of
      the 5-aminofluorescein would make these dyes interesting to explore as potential
      candidates for two photon excitation applications.

PMID- 15556559
TI  - A single-vial analytical and quantitative gas chromatography-mass spectrometry
      assay for terpene synthases.
AB  - A quantitative assay for the analysis of sesquiterpene synthases, wherein each
      reaction mixture is formulated in glass gas chromatography vials, overlaid with
      organic solvent such as ethyl acetate, and subsequently vortexed to extract
      hydrocarbon reaction products into the organic phase after a suitable incubation
      period, was developed. The product-enriched organic phase is then sampled in an
      automated fashion and injected directly into a gas chromatograph-mass
      spectrometer without further workup for analysis and quantification of
      hydrocarbon products. Application of the vial assay to the analysis of amorpha
      4,11-diene synthase (ADS), a sesquiterpene synthase, demonstrated the sensitivity
      of the assay for detection of major and minor reaction products and most notably
      for the identification of several sesquiterpene products that had escaped
      previous detection. A steady-state kinetic analysis of tobacco 5-epi
      aristolochene synthase (TEAS), another sesquiterpene synthase, validated the
      quantitative nature of the assay, providing an alternative means to the
      established method of using radiolabeled substrate, extraction, and scintillation
      counting. This simplified assay provides a standardized method to facilitate
      analysis of terpene synthases and diverse mutant enzyme libraries by supplanting
      the common practice of using larger scale reactions, multiple extractions, and
      evaporative concentration of the organic phase prior to gas chromatography-mass
      spectrometry (GC-MS) analysis.

PMID- 15556560
TI  - An activity-based probe for the determination of cysteine cathepsin protease
      activities in whole cells.
AB  - We describe a novel diazomethylketone-containing irreversible inhibitor (BIL-DMK)
      which is specific for a subset of pharmaceutically important cysteine cathepsin
      proteases. BIL-DMK rapidly inactivates cathepsins B, F, K, L, S, and V in
      isolated enzyme assays and labels cathepsins in whole cells. The presence of
      catalytically active cathepsins B, L, and K or S was demonstrated using
      radioiodinated BIL-DMK in HepG2 (hepatoma), HIG82 (rabbit synoviocyte), and Ramos
      (B lymphoma) cell lines, respectively. The identity of each protein labeled was
      confirmed from the isoelectric point and molecular mass of the radioactive spots
      on two-dimensional gel and by comigration with each cathepsin as identified by
      immunoblotting. These cell lines were used to establish whole-cell enzyme
      occupancy assays to determine the potency of both irreversible and reversible
      inhibitors against each cathepsin in their native cellular lysosomal or endosomal
      environment. These whole-cell enzyme occupancy assays are useful to determine the
      cellular permeability of competing inhibitors and have the advantage of not
      requiring specific substrates for each cathepsin of interest.

PMID- 15556561
TI  - Detection of binding partners to the profilin:actin complex by far Western and
      mass spectrometry analyses.
AB  - A method to search for interaction partners to the profilin:actin complex that
      can distinguish molecules that preferentially bind the complex from those that
      interact with profilin or actin separately is described. The procedure should be
      applicable for any situation where cell extracts or other complex samples are
      screened for the presence of protein molecules specifically recognizing a protein
      complex but having no or low affinity for its individual components. The method
      is readily combined with mass spectrometry for direct identification of detected
      proteins. In this study, Mena and Hsp70 were detected as interaction partners to
      profilin:actin.

PMID- 15556562
TI  - A high-performance liquid chromatography method for the analysis of intermediates
      of the deoxyxylulose phosphate pathway.
AB  - A sensitive and versatile ion pair radio high-performance liquid chromatography
      (HPLC) method for the investigation of the deoxyxylulose phosphate (DXP) pathway
      has been developed, allowing the simultaneous separation of phosphorylated,
      nonphosphorylated, and nucleotide moieties bearing intermediates. Moreover, this
      method addresses the problem of separating the isomers isopentenyl diphosphate
      (IDP) and dimethylallyl diphosphate (DMADP). Because the majority of the
      intermediates of this isoprenoid pathway lack a chromophore, the combination with
      an on-line radiodetector provides a highly sensitive tool for their detection.
      Chromoplasts isolated from Capsicum annuum and Narcissus pseudonarcissus served
      as model systems for the testing of the analytical procedures after the
      application of radiolabeled precursors. This HPLC system, which represents an
      improvement in analytical methods developed for the analysis of the mevalonic
      acid pathway, should be easily adaptable to other plant and bacterial systems and
      should permit further elucidation of the regulatory mechanisms that control the
      flow of intermediates through the DXP pathway and the coordination with related
      metabolic pathways. Moreover, the system can serve as an analytical tool in the
      screening for inhibitors of this pathway, allowing the development of new
      antibiotics as well as herbicides, because this pathway is absent in vertebrates.

PMID- 15556563
TI  - Positional-scanning combinatorial libraries of fluorescence resonance energy
      transfer peptides to define substrate specificity of carboxydipeptidases: assays
      with human cathepsin B.
AB  - We have developed positional scanning synthetic combinatorial libraries to define
      the substrate specificity of carboxydipeptidases. The library Abz-GXXZXK(Dnp)-OH,
      where Abz is ortho-aminobenzoic acid, K(Dnp) is N(epsilon)-2,4-dinitrophenyl
      lysine with free carboxyl group, the Z position was successively occupied with 1
      of 19 amino acids (cysteine was omitted), and X represents randomly incorporated
      residues, was assayed initially with human cathepsin B, and arginine was defined
      as one of the best residues at the P(1) position. To examine the selectivity of
      S(1)('), S(2), and S(3) subsites, the sublibraries Abz-GXXRZK(Dnp)-OH, Abz
      GXZRXK(Dnp)-OH, and Abz-GZXRXK(Dnp)-OH were then synthesized. The peptide Abz
      GIVRAK(Dnp)-OH, which contains the most favorable residues in the P(3)-P(1)(')
      positions identified by screening of the libraries with cathepsin B, was
      hydrolyzed by this enzyme with k(cat)/K(m)=7288 mM(-1)s(-1). This peptide is the
      most efficient substrate described for cathepsin B to this point, and it is
      highly selective for the enzyme among the lysosomal cysteine proteases.

PMID- 15556564
TI  - A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist
      and antagonist.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is an important
      therapeutic drug target against several diseases such as diabetes, inflammation,
      dyslipidemia, hypertension, and cancer. Ligand binding to PPARgamma is
      responsible for controlling the biological functions, and developing new
      technology to measure ligand-PPARgamma binding is significant for both the
      function study of the receptor and ligand discovery. In this study, we exploited
      an efficient approach for the discovery of PPARgamma agonist and antagonist via a
      yeast two-hybrid system based on the fact that PPARgamma interacts with the
      coactivator CBP (CREP-binding protein) ligand-dependently. We employed the MEL1
      reporter gene instead of the traditionally used LacZ gene to evaluate the protein
      protein interactions by conducting a convenient alpha-galactosidase assay in the
      yeast strain AH109 with genes of PPARgamma-LBD (ligand-binding domain) and CBP N
      terminus introduced. With this built screening platform, the EC(50) values of the
      PPARgamma agonists rosiglitazone, troglitazone, pioglitazone, indomethacin, 15
      deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)), and GI262570 were investigated,
      and the quantitatively antagonistic effect by IC(50) of the PPARgamma typical
      antagonist GW9662 on the rosiglitazone agonistic activity was fully examined. The
      reliability of this presented system evaluated by the comparable agreement of
      EC(50) and IC(50) values for the test compounds with the reported ones indicated
      that this yeast two-hybrid-based approach is powerful for PPARgamma agonist and
      antagonist screening. In addition, because this screening system is designed for
      use in a microtiter plate format where numerous chemicals could be readily
      screened, it is hoped that this yeast two-hybrid screening approach may be
      adaptable for high-throughput settings.

PMID- 15556565
TI  - High-quality RNA preparation for transcript profiling of osteocytes from native
      human bone microdissections.
AB  - Osteocytes, the most abundant bone cell type with important roles in tissue
      maintenance and pathological aberrations such as observed in bone metastases, are
      enclosed within a highly compact, calcified extracellular matrix. This location
      complicates analysis in native bone, with the consequence that despite their
      importance their in vivo molecular physiology is only poorly understood. We have
      examined the possibility of isolating osteocyte RNA for transcript profiling from
      native, frozen bone instead of employing the formalin-fixed, paraffin-embedded,
      decalcified version routinely used in histology, providing chemically modified
      and highly disintegrated RNAs. Bone tissue was tape-assisted cryosectioned and
      fixed to glass slides by support of UV-flash-triggered adhesive polymerization
      followed by quick hematoxylin-eosin staining to generate a guidance image for
      microdissection. Using an UVa-nitrogen laser, matrix-enclosed osteocytes were
      either excised and catapulted into RNA preparation vials or freed of accompanying
      nonosteocyte cellular material. The influences of bone sectioning, staining, and
      osteocyte capturing procedures on the prepared osteocyte RNAs were analyzed and
      the method was optimized accordingly. The obtained osteocyte RNAs showed the
      expected expression pattern of marker genes (reverse transcriptase-polymerase
      chain reaction), and, following conversion into fluorescent-labeled cDNAs, led to
      transcript profiles (cDNAchips; 2600 genes) with scatter-graph geometries
      indicating suitability for high-confidence evaluation. With the approach
      described here we introduce a methodological way for the characterization of the
      in vivo molecular physiology of osteocytes by functional genomics.

PMID- 15556566
TI  - Diosgenin dose-dependent apoptosis and differentiation induction in human
      erythroleukemia cell line and sedimentation field-flow fractionation monitoring.
AB  - To limit or stop cancer spreading, one of the most prevalent strategies is to
      induce cancer cell death. Differentiation therapy and apoptosis induction are two
      ways to achieve this goal. Sedimentation field-flow fractionation (SdFFF) has
      been described as an effective tool for cell separation, respecting integrity and
      viability. Because SdFFF takes advantage of intrinsic properties of eluted cells
      (size, density, shape), we studied the capacity of SdFFF to monitor specific
      biophysical modifications that occurred during cellular apoptosis or
      differentiation induction. Then, we used, as an in vitro cellular model of
      apoptosis and differentiation, diosgenin dose-dependent induction in the
      polyvalent human erythroleukemia cell line. Two other chemicals were used:
      phorbol myristate acetate (differentiation inducer) and staurosporine (apoptosis
      inducer). Our results demonstrated a correlation between SdFFF elution profile
      changes and induction of effective biological processes. Thus, after acquisition
      of a reference profile, SdFFF could be used alone to follow chemically induced
      biological events, suggesting many different applications such as testing series
      of molecules, evaluation of new cellular/biological models used in different life
      science fields, or sorting purified populations with the aim of better
      understanding mechanisms of induced cellular events.

PMID- 15556567
TI  - Sedimentation velocity analysis of highly heterogeneous systems.
AB  - This article discusses several improvements to the van Holde-Weischet (vHW)
      method [Biopolymers 17 (1978) 1387] that address its capability to deal with
      sedimentation coefficient distributions spanning a large range of s values. The
      method presented here allows the inclusion of scans early and late in the
      experiment that ordinarily would need to be excluded from the analysis due to
      ultracentrifuge cell end effects. Scans late in the experiment are compromised by
      the loss of a defined plateau region and by back-diffusion from the bottom of the
      cell. Early scans involve partial boundaries that have not fully cleared the
      meniscus. In addition, a major refinement of the algorithm for determining the
      boundary fractions is introduced, taking into account different degrees of radial
      dilution for different species in the system. The method retains its desirable
      model-independent properties (the analysis of sedimentation data does not require
      prior knowledge of a user-imposed model or range of sedimentation coefficients)
      and reports diffusion-corrected s value distributions, which can be presented
      either in a histogram format or the traditional integral distribution format.
      Data analyzed with the traditional vHW method are compared with those of the
      improved method to demonstrate the benefit from the added information in the
      analysis.

PMID- 15556568
TI  - An mRNA and DNA co-isolation method for forensic casework samples.
AB  - RNA analysis is expected to play an increasingly important role in the area of
      biomolecular forensic analysis. For example, mRNA expression analysis performed
      on a total RNA sample isolated from a biological stain may be used to identify
      the nature of the tissue(s) comprising the stain. Many of the physiological
      stains encountered at crime scenes involve heterogeneous mixtures of different
      body fluids (e.g., semen and saliva, semen and vaginal secretions). Separate
      sampling of these mixed stains from different "geographical" locations of the
      stains to isolate DNA and RNA could result in a misleading estimate of the ratio
      of the body fluids present and, in extreme cases, even fail to detect one of the
      contributors. Thus, a prerequisite for the use of mRNA expression profiling in
      routine forensic analysis is the ability to co-extract DNA and RNA from the same
      stain. This article describes an optimized method that was specifically developed
      to co-extract mRNA and DNA from the same physiological stain and that appears to
      be sufficiently sensitive and robust for routine forensic use.

PMID- 15556569
TI  - Oligonucleotides used as template calibrators for general application in
      quantitative polymerase chain reaction.
AB  - The optimizing and controlling for polymerase chain reactions (PCRs) requires
      standard target sequences to measure reaction specificity and to obtain accurate
      gene quantification. However, defined target sequences are often not readily
      available. This situation is particularly evident in the study of rare splice
      variant transcripts. For gains in efficiency and reaction speed, a small size of
      PCR amplicon typifies real-time PCR formats, including hydrolysis probes. This
      study demonstrates the use of oligonucleotides resembling one strand of complete
      amplicon sequences used in real-time PCR to provide sustainable and precise
      amounts of the target sequence without the necessity of enlisting nucleic acid
      cloning procedures. The application of template oligonucleotides is modeled using
      all of the splice variant forms of human vascular endothelial growth factor.

PMID- 15556570
TI  - Selecting transpositions using phage P1 headful packaging: new markerless
      transposons for functionally mapping long-range regulatory sequences in bacterial
      artificial chromosomes and P1-derived artificial chromosomes.
AB  - New Tn10 minitransposons were constructed to functionally map long-range
      transcription regulatory sequences in bacterial artificial chromosomes (BACs) and
      P1-derived artificial chromosomes (PACs). Each contained a wild-type loxP site
      but, significantly, contained no mammalian or bacterial genes and/or promoter
      elements within the transposed portion of DNA. In contrast to loxP transposons
      described previously, the new ones do not introduce transcription regulatory
      elements capable of interfering with those endogenous to the BAC clone in
      functional mapping studies. Progressive deletions from the loxP end of genomic
      DNA were efficiently generated using these transposons, and a series of
      truncations generated in a green fluorescence protein (GFP)-BAC fusion clone
      unambiguously identified three new long-range enhancer sequences functionally in
      the Nkx2-5 gene in transgenic mice. Insertions of these new transposons lacking
      antibiotic resistance genes into a BAC or PAC were indirectly selected by their
      ability to delete enough DNA from the clone so as to enable its packaging within
      a P1 phage head with both loxP sites intact for subsequent recovery of the large
      plasmid. The outcome of such an indirect mode of selection is both desirable and
      undesirable. First, because the screen is not antibiotic resistance marker
      dependent, the same transposon can be used to generate nested deletions
      efficiently in both BACs and PACs. Second, deletions through intrainsert
      recombinations unrelated to loxP/Cre also get packaged and recovered, and size
      analyses of the BAC/PAC vector band after NotI digestion is indispensable to
      identify authentic loxP/Cre deletions. The procedure nevertheless offers a
      potential approach to map recombinogenic sequences in BACs and PACs.

PMID- 15556571
TI  - Immobilized cofactor derivatives for kinetic-based enzyme capture strategies:
      direct coupling of NAD(P)+.
AB  - This study reevaluates the potential for direct coupling of NAD(P)(+) to a
      carboxylate-terminating spacer arm using carbodiimide-promoted coupling in an
      attempt to develop a greatly simplified synthetic method for cofactor
      immobilization that would support the more widespread adoption of kinetic-based
      enzyme capture (KBEC) strategies for protein purification applications and
      protein-detecting arrays/proteomic studies. Direct coupling of NAD(+) to epoxy
      (1,4-butanediol diglycidyl ether)-activated Sepharose is also described.
      Depending on the synthetic method used, the position of attachment of cofactor is
      concluded to be primarily through the pyrophosphate or ribosyl hydroxyl groups.
      Total substitution levels varied from 0.5 to 2 micromol/g wet weight with 28-67%
      accessibility. Model bioaffinity chromatographic studies employing KBEC
      strategies are reported for bovine heart L-lactate dehydrogenase, yeast alcohol
      dehydrogenase, l-phenylalanine dehydrogenase from Sporosarcina, glutamate
      dehydrogenase (GDH) from Candida utilis, and GDH from bovine liver. The NAD(+)
      derivative prepared using epoxy-activated Sepharose shows most potential for
      further development based on total substitution levels, the apparent absence of
      nonbiospecific interference, reversible biospecific adsorption of some of the
      test enzymes using soluble KBEC/stripping ligand tactics, and the relative
      simplicity of the synthetic method.

PMID- 15556572
TI  - Real-time monitoring of branched rolling-circle DNA amplification with peptide
      nucleic acid beacon.

PMID- 15556573
TI  - 26S rRNA-based internal control gene primer pair for reverse transcription
      polymerase chain reaction-based quantitative expression studies in diverse plant
      species.

PMID- 15556574
TI  - A continuous fluorescent method for measuring Na+ transport.

PMID- 15556575
TI  - Redetermination of the extinction coefficient of camphor-10-sulfonic acid, a
      calibration standard for circular dichroism spectroscopy.

PMID- 15556576
TI  - [Postoperative intraperitoneal adhesions: current and future status].

PMID- 15556577
TI  - [Radiotherapy and chemotherapy in the treatment of oesophageal carcinoma].
AB  - Surgery, chemotherapy and radiotherapy are the three major arms of treatment for
      cancer of the oesophagus, and combined modality therapy is required to treat
      advanced disease. Exclusive chemoradiotherapy is a feasible option for
      locoregionally advanced disease in responder patients. Elective surgery as a
      palliative procedure should not be regarded as a standard option in patients with
      metastatic or non-resectable oesophageal cancer. Surgery appears more and more as
      an adjuvant therapy in the curative treatment of oesophageal cancer, especially
      for advanced tumours.

PMID- 15556578
TI  - [Percutaneous ultrasound-guided drainage in the surgical treatment of acute
      severe pancreatitis].
AB  - AIM OF THE STUDY: To report results of percutaneous ultrasound-guided drainage,
      performed by a surgeon, in the treatment of complications of acute pancreatitis
      (AP), and to determine the role of this technique in the therapeutic
      armamentarium of severe AP. PATIENTS AND METHODS: From 1986 to 2001, 59 patients
      were included in this retrospective study. All patients initially had severe
      necrotizing AP (mean Ranson score = 4.1 ; range : 2-7). Anatomical lesions
      included pancreatic abscess in 6 patients and necrosis in 53 (17 stage D and 36
      stage E according to Balthazar's classification). Necrosis was infected in 42 and
      sterile in 11 respectively. Drainage was performed under ultrasound guidance and
      local anaesthesia using small-diameter drains (7-14 French). RESULTS: Drainage
      was performed on average 23 days after onset of AP. Infection was proven by fine
      needle aspiration in 47 (80 %) patients (41 infected necrosis and 6 localized
      abscess). In one patient, culture of aspirated fluid was negative but necrosis
      was infected (one false negative). Culture of aspirated fluid was negative and
      necrosis was sterile in 11 patients. Nineteen (32%) patients healed without
      subsequent surgery: 7 (16%) in the infected necrosis group, 6(55%) in the sterile
      necrosis group, and 6 (100%) in the abscess group. Forty (68%) patients had
      subsequent necrosectomy including 8 (14%) who died. Twenty (34 %) digestive
      fistulas healed spontaneously, except one treated by diversion stomia. Of the 16
      (27 %) pancreatic fistulas, 6 needed subsequent interventional treatment.
      CONCLUSION: In selected patients, percutaneous drainage can represent an
      alternative to surgery with a 14% mortality rate. The high rate of subsequent
      necrosectomy suggests that drains with larger diameter, possibly associated with
      continuous irrigation, should be used.

PMID- 15556579
TI  - [Laparoscopic adrenalectomy for large tumors].
AB  - AIM OF THE STUDY: To analyze indications and results of laparoscopic
      adrenalectomy for large tumors (> 6 cm). METHODS: It is a retrospective study
      including patients between January 1994 and December 2003 operated on for large
      adrenal lesions > or =6 cm. The size was given by the pathologist. All the
      patients had a flank transperitoneal approach. Analysed Parameters were:
      operative difficulties; operative time; conversion rate; postoperative morbidity,
      follow-up and histologic data. RESULTS: Fourteen patients (10 female and 4 male)
      were included. Mean age at the time of the diagnosis was 52 years (range: 17-79).
      Mean size of the lesions was 7 cm (range: 6-10 cm). Mean operative time was 132
      mn (range: 120-240 mn). None of the patients experienced surgical complications.
      Two conversions were needed (for vena cava attachments in one case and because of
      a retrocava localization in the other case). Three patients had morbidity: one
      intraperitoneal hemorrhage occurring at the second postoperative day and needing
      laparotomy; one left pneumopathy; and one case of neuralgia due to a port
      insertion. Mean hospital stay was 4,5 days. Histologic data showed: five
      ganglioneuromas, three pheochromocytomas, three adenomas, two adrenocortical
      carcinomas, and one postpancreatitis cytosteatonecrosis. CONCLUSION: Laparoscopic
      adrenalectomy is feasible for large lesions > or =6 cm when no evidence of
      malignity is demonstrated neither by the preoperative imaging study nor by the
      surgical exploration.

PMID- 15556580
TI  - [Interest of sentinel lymph node biopsy for the staging of ductal carcinoma in
      situ].
AB  - PURPOSE: The aim of this study was to define the interest of sentinel lymph node
      biopsy (SLNB) for the staging of ductal carcinoma in situ (DCIS) and DCIS with
      micro-invasion (DCISM) in patients with breast carcinoma. MATERIAL AND METHODS:
      From June 1999 to December 2002 we listed, in a retrospective study, 52 patients
      treated surgically for a DCIS or a DCISM. All except one had an histology before
      surgery, and all had SLNB. Intraoperative imprint cytology of the sentinel lymph
      node (SLN) was performed then there were analysed by staining with hematoxylin
      eosin. Patients with positive SLN underwent complete axillary dissection.
      RESULTS: It was removed an average of three SLNs by patient (extreme 1 to 6).
      Metastases in the SLN were detected in four (7,7%) of the 52 patients, including
      three cases had only micrometastases in the SLN. In the four patients treated
      with complete axillary dissection, the SLN were the only positives nodes.
      CONCLUSION: The SLNB for DCIS and DCISM increases the involvement rate of lymph
      node. Because of the widespread for early detection of breast cancer, it is noted
      a regular increase in the rate of DCIS. Even if the attitude to be had towards
      the lymph node metastases in these cases is not yet well defined, and so only 2%
      of the patients approximately die of this pathology, it is interesting because of
      increase in absolute value of mortality, to try to improve the prognosis criteria
      to modify the treatment of this pathology.

PMID- 15556581
TI  - [Visceral adhesion after intraperitoneal ventral hernia treatment: monocentric
      study comparative of protected versus unprotected meshes].
AB  - AIM OF THE STUDY: Intraperitoneal (IP) ventral hernia repair is advantageous
      because of reduced dissection, shorter operative time and less postoperative
      pain. However, the IP positioning of the mesh is suspected to increase the risk
      of visceral adhesion and induce complications. To overcome these drawbacks, an
      innovative mesh: Parietex Composite (RC) was developed with one side protected by
      a hydrophilic resorbable film. The purpose of this study was to compare using
      ultrasonography the rate of visceral adhesions after IP placement of a
      conventional mesh (RP) versus RC mesh. PATIENTS AND METHODS: Twenty-six patients
      who received a Parietex Composite were prospectively compared to a retrospective
      series of 26 consecutive asymptomatic patients who received a non protected
      polyester mesh (RP). In order to objectively assess visceral adhesion toward the
      abdominal wall, an ultrasound specific examination was used after previous
      validation by comparison of preoperative ultrasonographic data with peroperative
      gross appearance in both groups. RESULTS: With a mean follow up of 33 months,
      both groups were equivalent in term of inclusion criteria excepted for age which
      was older the RP group. US validation data were: sensitivity 72%, accuracy 69%,
      negative predictive value 67%. Using this procedure, 81% of the patients exhibit
      visceral adhesion to the mesh in the RP group, versus 27% in the PC group (P
      =0.0002, chi2). CONCLUSION: US examination represents a suitable tool to evaluate
      postoperative adhesions to the abdominal wall. A significant reduction of
      visceral adhesion in the RC group was shown.

PMID- 15556582
TI  - [Routine or selective intraoperative cholangiography during laparoscopic
      cholecystectomy].

PMID- 15556583
TI  - [Spontaneous splenic rupture due to splenic metastasis of lung cancer].
AB  - We report the case of a patient who underwent splenectomy for spontaneous rupture
      of the spleen due to splenic metastasis. Pathologic examination revealed diffuse
      infiltration by carcinoma. Chest X-ray revealed a right lung superior lobe tumor,
      related to poorly differentiated carcinoma. Total splenectomy is a good option
      for diagnosis and treatment of splenic metastases.

PMID- 15556584
TI  - [Interest of thyroidectomy in the management of thyroglossal duct cysts].
AB  - PURPOSE OF STUDY: To discuss the authors' experience with thyroglossal duct (TD)
      carcinoma and expose the interest of the thyroidectomy in the management of this
      entity. PATIENTS AND METHODS: A retrospective review of all patients with the
      diagnosis of TD operated on from 1985 to 2002 was performed. RESULTS: Four cases
      of papillary TD carcinoma were identified. Two patients were treated by a
      Sistrunk procedure associated with total thyroidectomy. One patient needed a
      thyroidectomy fifteen years after the initial management of the papillary
      thyroglossal duct carcinoma. The last patient had a medical treatment, with no
      evidence of complication after eleven years of follow up. CONCLUSION: A
      microscopic focus of papillary carcinoma, without cyst wall invasion, can be
      managed by a Sistrunk procedure, with the need for long-term follow up. Treatment
      of all other thyroglossal duct papillary carcinomas should include thyroidectomy
      followed by radioactive iodine treatment.

PMID- 15556585
TI  - [Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas. A
      case report].
AB  - Undifferentiated carcinoma with osteoclast-like giant cells is a rare pancreatic
      neoplasm, with a possible cystic pattern, includes an adenocarcinoma component
      and giant cell mimicking osteoclastic bone tumor. We report the case of a 72-year
      woman admitted for jaundice and epigastric pain. Abdominal ultrasound and
      computed tomography scan revealed a 6 x 5 cm cystic and solid tumor of the
      pancreatic head with both bile duct and pancreatic duct dilatation. A
      pancreaticoduodenectomy was performed and pathologic examination revealed an
      undifferentiated carcinoma with osteoclast-like giant cells of the pancreatic
      head. The patient was alive and disease-free with a 18-month follow-up.

PMID- 15556586
TI  - [Surgical treatment of peritoneal carcinomatosis].
AB  - Surgical treatment of peritoneal carcinomatosis with curative intent involves the
      resection of all macroscopic malignant tissue and the treatment of microscopic
      residual tissue with local chemotherapy. Intraperitoneal chemotherapy is
      efficient only when associated with hyperthermia. This article details the
      technical aspect of intraperitoneal chemohyperthermia. These techniques involve
      specific and important features. At these conditions, peritoneal carcinomatosis
      can be cured in two-thirds of cases.

PMID- 15556587
TI  - Multi-slice CT contrast enhancement regimens.
AB  - Historically, the development of progressively faster Computed Tomography (CT)
      technology has dictated a recurrent need to re-examine intravenous contrast agent
      enhancement regimens. The most recently introduced development, the very fast,
      multi-slice helical/spiral systems, have raised the same issue yet again. It is
      possible, exploiting the technology to its maximum potential as regards speed, to
      perform an examination many times faster (depending on the number of detector
      rings from 4 to 64) even than with earlier single slice spiral instruments. In
      order to optimise image quality, such maximal speed gains will not usually be
      sought but, nevertheless, imaging time will generally be substantially reduced.
      It is natural that the question of a possible need to modify contrast agent
      enhancement protocols designed for an earlier generation of slower machines
      should again be considered. Using as a basis known contrast agent
      pharmacokinetics and results of modelling techniques, the matter is tackled in
      this paper.

PMID- 15556588
TI  - Texture analysis of medical images.
AB  - The analysis of texture parameters is a useful way of increasing the information
      obtainable from medical images. It is an ongoing field of research, with
      applications ranging from the segmentation of specific anatomical structures and
      the detection of lesions, to differentiation between pathological and healthy
      tissue in different organs. Texture analysis uses radiological images obtained in
      routine diagnostic practice, but involves an ensemble of mathematical
      computations performed with the data contained within the images. In this article
      we clarify the principles of texture analysis and give examples of its
      applications, reviewing studies of the technique.

PMID- 15556589
TI  - Sonographic assessment of the submandibular space.
AB  - There is a wide variety of pathological processes which may present with swelling
      in the submandibular space. Although the submandibular gland is the most
      important structure in this region, there are a number of extraglandular causes
      of swelling which frequently mimic submandibular gland enlargement. In this
      review the use of high-resolution ultrasound in the assessment of the
      submandibular gland and adjacent structures is discussed and illustrated.

PMID- 15556590
TI  - MRI of osteonecrosis.
AB  - Osteonecrosis is a relatively common condition, which may be idiopathic or
      secondary to a variety of clinical situations. It may involve the subarticular
      region of a joint, when it is commonly referred to as ischaemic necrosis, or the
      metaphyseal regions of long bones, when it is referred to as bone infarction. In
      both situations, early lesions may be radiographically occult. However, magnetic
      resonance imaging (MRI) is very sensitive in identifying and characterizing
      osteonecrosis. This review illustrates the varied MRI features of osteonecrosis
      that enable a confident diagnosis to be made. Complications and differential
      diagnosis are also considered.

PMID- 15556591
TI  - Patterns of metastatic breast carcinoma: influence of tumour histological grade.
AB  - AIM: To assess if the pattern of metastatic spread of carcinoma of the breast
      varies according to tumour histological grade. MATERIALS AND METHODS: The
      clinical details, histological features of the primary tumour, and imaging
      findings at presentation of patients with metastatic breast cancer have been
      recorded prospectively since 1997. The pattern of metastatic spread, age at
      metastasis, metastasis-free interval (MFI), and length of survival with
      metastases were analysed by tumour grade. RESULTS: There was a significant
      association between histological high-grade tumours and high frequency of intra
      pulmonary metastases (p=0.013); liver metastases (p=0.039); para-aortic
      lymphadenopathy (p=0.022) and metastatic presentation under 50 years of age
      (p=0.003). A significant correlation was also demonstrated between histological
      low-grade tumours and increased frequency of pleural disease (p=0.020); increased
      frequency of bone metastases (p=0.004); prolonged MFI (MFI>5 years; p<0.0001);
      and increased length of survival (p<0.0001). CONCLUSION: There is a correlation
      between patterns of metastatic spread and tumour histological grade. This partly
      explains the negative prognostic value of high tumour grade, as metastases from
      grade 3 tumours more commonly occur at sites associated with a worse prognosis.
      This finding may also prove useful in interpreting imaging in patients who have a
      history of breast cancer and undergo subsequent imaging because of new symptoms.

PMID- 15556592
TI  - Assessing the impact of CAD on the sensitivity and specificity of film readers.
AB  - AIM: To assess the impact of computer-aided detection (CAD) prompts on film
      readers' sensitivity and specificity. MATERIAL AND METHODS: Thirty-five readers
      read 120 films, including 44 cancers, 40 of which were prompted. All readers
      looked at all cases with and without prompts. The sensitivity and specificity
      were calculated for each reader under each condition. RESULTS: The sensitivity
      improved when CAD prompts were used (0.80 from 0.77). The difference was slightly
      below the threshold for statistical significance (95% CI for the difference is 
      0.0027-0.064). The specificity also improved (0.86 from 0.85), but not
      significantly. There was a significant improvement in sensitivity when readers'
      judgements were combined to simulate double reading, from 0.77 to 0.81. (95% CI
      for the difference is 0.014-0.077). CONCLUSIONS: Analysis of prompted cancers
      that readers did and did not recall, found that cases were more likely to be
      correctly recalled if there were emphasized prompts, more prompts or if the case
      was harder. There was no statistically significant effect for type of abnormality
      or tumour size or for the performance, attitude or experience of the reader.

PMID- 15556593
TI  - Bispectral index monitoring for conscious sedation in intervention: better,
      safer, faster.
AB  - AIM: The aim of this study was to compare subjective (Ramsay sedation score, RSS)
      with objective electroencephalogram-based bispectral index (BIS) assessment, and
      to validate the appropriate BIS range for measurement of conscious sedation in
      interventional procedures. MATERIALS AND METHODS: One hundred patients undergoing
      sedo-analgesia (midazolam and fentanyl) for interventional gastrointestinal
      procedures were divided into two groups. In group A (n=30) sedation was guided by
      the RSS with the operator blinded to the BIS recording. In group B (n=70) the
      operator titrated intravenous sedation to maintain an optimal BIS, predetermined
      from the results in group A. Recovery time, procedure duration, physiological
      parameters and unplanned events were recorded in both groups. RESULTS: There was
      a significant correlation between the BIS and RSS (p<0.001). BIS values of 87.2
      and 80.9 corresponded to an RSS of 3 and 4, respectively. The optimal BIS level
      was defined as 80-85. Fifty-seven point five percent of readings were within this
      range in group B compared with 26.5% in group A (p<0.001). Sedation approaching
      general anaesthesia (BIS<60) occurred in 5.5% of patients in group A but not in
      group B. Mean recovery time, duration of procedure, midazolam and fentanyl doses
      were significantly reduced in group B. Unplanned events were reduced from 27 to
      17%, but this was not statistically significant (p=0.29). CONCLUSION: BIS
      monitoring enables more effective titration of sedatives to maintain a suitable
      level of consciousness, whilst reducing procedure time. The BIS offers an
      objective, safe and reliable measure of sedation, without disturbing either
      patient or operator. BIS monitoring raises the standard of patient care, and in
      our view, should be used to augment standard assessment.

PMID- 15556594
TI  - Corroboration of in utero MRI using post-mortem MRI and autopsy in foetuses with
      CNS abnormalities.
AB  - AIMS: To corroborate the findings of in utero magnetic resonance imaging (MRI)
      with autopsy and post-mortem MRI in cases of known or suspected central nervous
      system (CNS) abnormalities on ultrasound and to compare the diagnostic accuracy
      of ante-natal ultrasound and in utero MRI. METHODS: Twelve pregnant women, whose
      foetuses had suspected central nervous system abnormalities underwent in utero
      MRI. The foetuses were imaged using MRi before autopsy. The data were used to
      evaluate the diagnostic accuracy of in utero MRI when compared with a reference
      standard of autopsy and post-mortem MRI in 10 cases and post-mortem MRI alone in
      two cases. RESULTS: The diagnostic accuracy of antenatal ultrasound and in utero
      MRI in correctly characterizing brain and spine abnormalities were 42 and 100%,
      respectively. CONCLUSION: In utero MRI provides a useful adjuvant to antenatal
      ultrasound when assessing CNS abnormalities by providing more accurate anatomical
      information. Post-mortem MRI assists the diagnosis of macroscopic structural
      abnormalities.

PMID- 15556595
TI  - The relationship between solitary pulmonary nodules and bronchi: multi-slice CT
      pathological correlation.
AB  - AIM: To investigate the relationship between solitary pulmonary nodules (SPN) and
      bronchi and its value in predicting the nature of the SPN. MATERIALS AND METHODS:
      We performed volumetric targeted scans of 0.5 mm collimation with multi-slice
      computed tomography (MSCT), reconstructing multiplanar reconstructions (MPR),
      curved multiplanar reconstructions (CMPR) and surface-shaded display (SSD) images
      of bronchi in 78 consecutive patients with SPN (53 malignant and 25 benign) and
      correlated the findings with those of macroscopic and microscopic specimens.
      RESULTS: With this CT protocol, the third to seventh-order bronchi were shown
      continuously and very clearly in all patients. CT findings were consistent with
      those of specimens. CT demonstrated the relationship between the SPN and bronchi
      in 46 (86.8%) malignant and 18 (75.0%) benign nodules. Five types of tumour
      bronchus relationships were identified with MSCT. Type I: the bronchus was
      obstructed abruptly by the SPN; type II: the bronchus penetrated into the SPN
      with tapered narrowing and interruption; type III: the bronchial lumen shown
      within the SPN was patent and intact; type IV: the bronchus ran around the
      periphery of the SPN with intact lumen; type V: the bronchus was displaced,
      compressed and narrowed by the SPN. Malignant nodules were most commonly of type
      I (58.5%), secondly of type IV (26.4%) and rarely of type V (1.9%). Benign
      nodules were most often of type V (36.0%), followed by type III (20.0%), type I
      (16.0%), and there were no type II. Types I, II and IV were more common in
      malignant nodules, whereas type V was seen more frequently seen in benign nodules
      (p<0.05). There was no statistically significant difference between the two
      groups regarding type III. CONCLUSION: Ultra-thin section with MSCT and MPR, CMPR
      and SSD reconstruction can improve the demonstration of the patterns of tumour
      bronchus relationships, which can reflect the pathological changes of the nodules
      to some extent and help differentiate malignant from benign tumours.

PMID- 15556596
TI  - Endovascular treatment of superficial femoral artery occlusive disease with
      stents coated with diamond-like carbon.
AB  - A major consideration in the reduction of early stent thrombosis and in-stent
      restenosis is the improvement of biocompatibility of the devices. Diamond-like
      carbon is a novel material for coating stent surfaces in order to increase
      biocompatibility. The authors report on the endovascular treatment of two
      individuals with superficial femoral artery occlusions, using stents coated with
      diamond-like carbon. Technical and clinical success was achieved in both cases,
      with primary patency rates of 100% 12 months after intervention.

PMID- 15556597
TI  - Simple evaluation of liver size on erect abdominal plain radiography.

PMID- 15556598
TI  - Erdheim-Chester disease versus multifocal fibrosis and Ormond's disease: a
      diagnostic dilemma.
AB  - AIM: The aim of the study was to evaluate the effectiveness of different imaging
      techniques with respect to diagnosis and differential diagnosis between Erdheim
      Chester disease (ECD) and multifocal fibrosis (MF)/Ormond's disease (OD). METHOD:
      Three cases of ECD were included, two of which were misdiagnosed as MF/OD.
      Findings in different imaging techniques [plain radiography, skeletal
      scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI)] of
      the lower extremities, chest MRI, craniofacial MRI, abdominal CT and MRI) were
      compared and ranked with regard to diagnostic efficacy. RESULTS: Differentiation
      between ECD and MF/OD is only possible by imaging the long bones. Bone
      roentgenograms and skeletal scintigraphy, followed by MRI and CT of the lower
      extremities are the most effective imaging techniques. CONCLUSION: A low
      threshold for carrying out plain radiography of the lower limbs in case of RF/MF
      will increase the number of ECD-cases.

PMID- 15556599
TI  - Eccrine acrospiroma of breast: mammographic and ultrasound findings.

PMID- 15556600
TI  - Re: Should ultrasound examinations be performed by non-radiologists?

PMID- 15556601
TI  - Cardiac pacing systems and implantable cardiac defibrillators (ICDs): a
      radiological perspective of equipment, anatomy and complications.

PMID- 15556602
TI  - The power of vanadate in crystallographic investigations of phosphoryl transfer
      enzymes.
AB  - The formation of transition state mimics of phosphoryl transfer reactions with
      the metal oxoanion vanadate is a powerful technique in macromolecular
      crystallography. The tendency of vanadate to form pentacovalent complexes
      exhibiting trigonal bipyramidal geometry makes this compound a close
      approximation of the transition state for such reactions. In many cases, vanadate
      complexes provide the most accurate visualization of the transition state that
      can be reasonably achieved. A survey of the Protein Data Bank reveals that a
      relatively small number of structures (39, representing 23 unique proteins)
      include vanadate, yet these structures represent four of the six E.C. categories
      of enzymes, and were obtained in crystals with pH values ranging from 5.0 to 7.8.
      Vanadate has additional advantages over other compounds such as aluminum
      fluoride, beryllium fluoride and nitrate used for visualization of transition
      state mimics in that vanadate readily forms covalent bonds with a variety of
      ligands and has produced a wider variety of transition state mimics. Given the
      hundreds of crystal structures that have been solved for phosphoryl transfer
      enzymes, it is surprising that vanadate has not been used more frequently for
      visualization of transition state analogs. We propose that an opportunity exists
      for vanadate to become a more commonly utilized component of the macromolecular
      crystallographer's toolbox.

PMID- 15556603
TI  - Ycf1-dependent cadmium detoxification by yeast requires phosphorylation of
      residues Ser908 and Thr911.
AB  - Yeast cadmium factor (Ycf1), an ATP-binding cassette (ABC) protein of the
      multidrug resistance protein subfamily, is a vacuolar GS-conjugate transporter
      required for heavy metal and drug detoxification. There is evidence that
      phosphorylation may play a critical role in the function of ABC transporters from
      higher organisms. In this work, the possibility of Ycf1 phosphorylation was
      examined using site-directed mutagenesis. We demonstrate that Ser908 and Thr911,
      within the regulatory domain (R domain), are functionally important for Ycf1
      transport activity and likely sites for phosphorylation. Mutation of these
      residues to alanine severely impaired the Ycf1-dependent cadmium detoxification
      capacity and transport activity, while replacement by acidic residues (mimicking
      phosphorylation) significantly suppressed the cadmium resistance and transport
      defects. Both in vitro treatment of Ycf1 with alkaline phosphatase and changes in
      the electrophoretic mobility of the S908A, T911A and double mutant S908A/T911A
      proteins supported the conclusion that Ycf1 is a phosphoprotein. The screening of
      the yeast kinome identified four protein kinases affecting cadmium
      detoxification, but none of them was involved directly in the phosphorylation of
      Ycf1. Our data strongly implicate Ycf1 phosphorylation as a key determinant in
      cadmium resistance in yeast, a significant finding given that very little is
      known about phosphorylation of ABC transporters in yeast.

PMID- 15556604
TI  - SHP2 binds catalase and acquires a hydrogen peroxide-resistant phosphatase
      activity via integrin-signaling.
AB  - Here, we examined whether catalase binds SHP2 and alters SHP2 susceptibility to
      H2O2. Our results indicated that serum and fibrinogen commonly evoked catalase
      binding to SHP2 in HeLa and A549 cells in a herbimycin-A and TNFalpha sensitive
      manner. Expression of active catalase nearly 15-fold over control levels in tet
      off HeLa cells substantially increased the SHP2 binding, and the catalase
      associated SHP2 displayed significantly high phosphatase activities with a H2O2
      resistance compared to those with little catalase. Site-directed mutagenesis at
      280 abolished the binding capability of catalase to SHP2-SH2 in vitro. These
      results suggest that catalase-280pYIQV binds SHP2 via integrin-signaling to
      increase a H2O2-resistant SHP2 activity.

PMID- 15556605
TI  - Sphingosine 1-phosphate transactivates c-Met as well as epidermal growth factor
      receptor (EGFR) in human gastric cancer cells.
AB  - Receptor tyrosine kinases (RTKs) are transactivated by the stimulation of G
      protein-coupled receptors (GPCRs). Sphingosine 1-phosphate (S1P), a ligand of
      GPCR, is known as a tumor-promoting lipid, but its signaling pathways are not
      fully understood. We here demonstrated that S1P induces rapid and transient
      tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and c-Met in
      gastric cancer cells, both of which have been proposed as prognostic markers of
      gastric cancers. The pathway of S1P-induced c-Met transactivation is Gi
      independent and matrix metalloproteinase-independent, which differs from that of
      EGFR transactivation. Our results indicate that S1P acts upstream of various RTKs
      and thus may act as a potent stimulator of gastric cancer.

PMID- 15556606
TI  - Analysis of estrogen receptor alpha signaling complex at the plasma membrane.
AB  - There is accumulating evidence that the estrogen receptor (ER) can transduce
      specific signals at the plasma membrane. We tried to clarify the biological
      function of ER as a signaling molecule by identifying proteins that interact with
      the membrane-localized ER. The activation function 1 and 2 (AF-1 and AF-2)
      domains of ERalpha with or without the membrane-targeting sequence were stably
      expressed in the breast cancer cell line, MCF-7. The level of tyrosine
      phosphorylation of AF-2 was significantly elevated by the membrane localization.
      By mass-spectrometry analysis, alpha- and beta-tubulins and heat shock protein 70
      were identified as the AF-1-associated proteins. Of these, tubulins are
      associated only with membrane-targeted AF-1.

PMID- 15556607
TI  - Transgenic plant-derived siRNAs can suppress propagation of influenza virus in
      mammalian cells.
AB  - As an example of the cost-effective large-scale generation of small-interfering
      RNA (siRNAs), we have created transgenic tobacco plants that produce siRNAs
      targeted to the mRNA of the non-structural protein NS1 from the influenza A virus
      subtype H1N1. We have investigated if these siRNAs, specifically targeted to the
      5'-portion of the NS1 transcripts (5mNS1), would suppress viral propagation in
      mammalian cells. Agroinfiltration of transgenic tobacco with an Agrobacterium
      strain harboring a 5mNS1-expressing binary vector caused a reduction in 5mNS1
      transcripts in the siRNA-accumulating transgenic plants. Further, H1N1 infection
      of siRNA-transfected mammalian cells resulted in significant suppression of viral
      replication. These results demonstrate that plant-derived siRNAs can inhibit
      viral propagation through RNA interference and could potentially be applied in
      control of viral-borne diseases.

PMID- 15556608
TI  - Reduced adipose tissue mass and hypoleptinemia in iNOS deficient mice: effect of
      LPS on plasma leptin and adiponectin concentrations.
AB  - The aim of this study was to evaluate the impact of the lack of inducible NO
      synthase (iNOS) on body weight and adipose tissue mass as well as on plasma
      leptin and adiponectin in basal conditions and 6 h after lipopolysaccharide (LPS)
      administration in mice. Body weight was not different among male, six-week-old
      wild-type (WT) and iNOS-/- animals. However, the amount of epididymal white
      adipose tissue (EWAT) in iNOS-/- mice was significantly reduced (P<0.05).
      Circulating leptin and leptin mRNA in EWAT were decreased in iNOS-/- mice (P<0.05
      and P<0.01, respectively). Plasma adiponectin and adiponectin mRNA were
      unchanged. LPS administration increased plasma leptin in both genotypes (P<0.05).
      Neither genotype nor treatment changed plasma adiponectin. In summary, iNOS-/-
      mice exhibited normal body weight but reduced adipose mass accompanied by
      hypoleptinemia. Leptin responsiveness to LPS in iNOS-/- mutants is preserved,
      showing that the LPS-induced rise in leptin is independent of the presence of
      functional iNOS. In addition, iNOS deficiency or LPS does not influence
      expression and circulating levels of adiponectin.

PMID- 15556609
TI  - Effect of IGF-1 on the balance between autophagy of dysfunctional mitochondria
      and apoptosis.
AB  - Mutations in mitochondrial DNA (mtDNA) cause excessive production of
      mitochondrial reactive oxygen species (ROS) and shorten animal life span. We
      examined the mechanisms responsible for removal of mitochondria with deleterious
      mtDNA mutations by autophagy. Incubation of primary cells and cell lines in the
      absence of serum promotes autophagy of mitochondria with deleterious mtDNA
      mutations but spares their normal counterparts. The effect of serum withdrawal on
      the autophagy of dysfunctional mitochondria is prevented by the addition of IGF
      1. As a result of the elimination of mitochondria with deleterious mutations,
      excessive ROS production, characteristic of dysfunctional mitochondria, is
      greatly reduced. Mitochondrial autophagy shares a common mechanism with
      mitochondrial-induced cell apoptosis, including mitochondrial transition pore
      formation and increased ROS production.

PMID- 15556610
TI  - Overexpression of transglutaminase 2 accelerates the erythroid differentiation of
      human chronic myelogenous leukemia K562 cell line through PI3K/Akt signaling
      pathway.
AB  - Transglutaminase 2 (TG2) is a GTP-binding protein with transglutaminase activity.
      Despite advances in the characterization of TG2 functions and their impact on
      cellular processes, the role of TG2 in Human chronic myelogenous leukemia K562
      cell line is still poorly understood. To understand the biological significance
      of TG2 during the differentiation of K562 cells, we established and characterized
      K562 cells that specifically express TG2. Non-transfected K562 cells showed the
      increase of membrane-bound-TG2 level after 3 days in the response to Hemin and
      all trans-retinoic acid (tRA), indicating that membrane recruitment of TG2 is
      occurred during the erythroid differentiation. However, membrane recruitment of
      TG2 in TG2-transfected cells revealed within earlier time period, compared with
      that in vector-transfected cells. The ability of membrane-bound-TG2 to be
      photoaffinity-labeled with [alpha-32P]GTP was also increased in TG2-transfected
      cells. TG2-transfected cells activated Akt phosphorylation and inactivated ERK1/2
      phosphorylation, compared with vector-transfected cells. Furthermore,
      phosphorylation of CREB, one of the Akt substrates, was increased in TG2
      transfected cells and this phenomenon was confirmed by RT-PCR analysis of several
      marker genes related with erythroid lineage in the absence of PI3K specific
      inhibitor, Wortmannin, indicating that PI3K/Akt signaling pathway also involved
      in the differentiation of the cell. Finally, as results of benzidine positive
      staining as well as hemoglobinization analysis, overexpression of TG2 revealed
      acceleration of the erythroid differentiation of K562 cells. Taken together,
      there was no increased TG2 expression level in the response of Hemin/tRA and
      delayed differentiation in vector transfected cells than in TG2-transfected
      cells, suggesting that suppression of TG2 expression may retard the erythroid
      differentiation of K562 cells. Therefore, our study may give a new insight for
      another aspect of the development of this disease.

PMID- 15556611
TI  - Cations modulate the substrate specificity of bifunctional class I O
      methyltransferase from Ammi majus.
AB  - Caffeoyl-coenzyme A O-methyltransferase cDNA was cloned from dark-grown Ammi
      majus L. (Apiaceae) cells treated with a crude fungal elicitor and the open
      reading frame was expressed in Escherichia coli. The translated polypeptide of
      27.1-kDa shared significant identity to other members of this highly conserved
      class of proteins and was 98.8% identical to the corresponding O
      methyltransferase from parsley. For biochemical characterization, the recombinant
      enzyme could be purified to apparent homogeneity by metal-affinity
      chromatography, although the recombinant enzyme did not contain any affinity tag.
      Based on sequence analysis and substrate specificity, the enzyme classifies as a
      cation-dependent O-methyltransferase with pronounced preference for caffeoyl
      coenzyme A, when assayed in the presence of Mg2+-ions. Surprisingly, however, the
      substrate specificity changed dramatically, when Mg2+ was replaced by Mn2+ or
      Co2+ in the assays. This effect could point to yet unknown functions and
      substrate specificities in situ and suggests promiscuous roles for the lignin
      specific cluster of plant O-methyltransferases.

PMID- 15556612
TI  - The pur6 gene of the puromycin biosynthetic gene cluster from Streptomyces
      alboniger encodes a tyrosinyl-aminonucleoside synthetase.
AB  - The pur6 gene of the puromycin biosynthetic gene (pur) cluster from Streptomyces
      alboniger is shown to be essential for puromycin biosynthesis. Cell lysates from
      this mycelial bacterium were active in linking L-tyrosine to both 3'-amino-3'
      deoxyadenosine and N6,N6-dimethyl-3'-amino-3'-deoxyadenosine with a peptide-like
      bond. Identical reactions were performed by cell lysates from Streptomyces
      lividans or Escherichia coli transformants that expressed pur6 from a variety of
      plasmid constructs. Physicochemical and biochemical analyses suggested that their
      products were tridemethyl puromycin and O-demethylpuromycin, respectively.
      Therefore, it appears that Pur6 is the tyrosinyl-aminonucleoside synthetase of
      the puromycin biosynthetic pathway.

PMID- 15556613
TI  - Development of a tightly regulated U6 promoter for shRNA expression.
AB  - Short hairpin RNAs (shRNAs) have been used to achieve stable target knockdown in
      a variety of biological systems. Here, we report the development of a tightly
      regulated tetracycline-responsive human U6 promoter for shRNA expression. By
      engineering two copies of the tet operators flanking the TATA box of the human U6
      promoter, we created a U6 promoter derivative (2O2) that exhibited much lower
      basal transcriptional activity compared with recently reported inducible pol III
      dependent promoters. As a consequence of its tighter regulation, the 2O2 system
      greatly improved the success rate in making inducible knockdown cell lines.

PMID- 15556614
TI  - Cysteine and keto acids modulate mosquito kynurenine aminotransferase catalyzed
      kynurenic acid production.
AB  - Kynurenine aminotransferase (KAT) catalyzes the formation of kynurenic acid
      (KYNA), the natural antagonist of ionotropic glutamate receptors. This study
      tests potential substrates and assesses the effects of amino acids and keto acids
      on the activity of mosquito KAT. Various keto acids, when simultaneously present
      in the same reaction mixture, display a combined effect on KAT catalyzed KYNA
      production. Moreover, methionine and glutamine show inhibitory effects on KAT
      activity, while cysteine functions as either an antagonist or an inhibitor
      depending on the concentration. Therefore, the overall level of keto acids and
      cysteine might modulate the KYNA synthesis. Results from this study will be
      useful in the study of KAT regulation in other animals.

PMID- 15556615
TI  - Probing the active site of homoserine trans-succinylase.
AB  - Homoserine trans-succinylase is the first enzyme in methionine biosynthesis of
      Escherichia coli and catalyzes the activation of homoserine via a succinylation
      reaction. The in vivo activity of this enzyme is subject to tight regulation by
      several mechanisms, including repression and activation of gene expression,
      feedback inhibition, temperature regulation and proteolysis. This complex
      regulation reflects the key role of this enzyme in bacterial metabolism. Here, we
      demonstrate--using proteomics and high-resolution mass spectrometry--that
      succinyl is covalently bound to one of the two adjacent lysine residues at
      positions 45 and 46. Replacing these lysine residues by alanine abolished the
      enzymatic activity. These findings position the lysine residues, one of which is
      conserved, at the active site.

PMID- 15556616
TI  - S100B-modulated Ca2+-dependent ROS-GC1 transduction machinery in the gustatory
      epithelium: a new mechanism in gustatory transduction.
AB  - Gustatory transduction is a biochemical process by which the gustatory signal
      generates the electric signal. The microvilli of the taste cells in the gustatory
      epithelium are the sites of gustatory transduction. This study documents the
      biochemical, molecular, and functional identity of the Ca2+-modulated membrane
      guanylate cyclase transduction machinery in the bovine gustatory epithelium. The
      machinery is a two-component system: the Ca2+-sensor protein, S100B; and the
      transducer, ROS-GC1. S100B senses increments in free Ca2+, undergoes
      conformational change, binds to the domain amino acids (aa) Gly962-Asn981 and via
      the transduction domain aa Ile1030-Gln1041 activates ROS-GC1, generating the
      second messenger, cyclic GMP. In a recent study, operational presence of this
      machinery has been demonstrated in the photoreceptor bipolar synapse [Duda et
      al., EMBO J. 21 (2002) 2547]. Thus, the machinery has a broader role in sensory
      perceptions, vision in the retinal neurons and gustation in the tongue. The entry
      of the ROS-GC transduction machinery defines the beginning of a new paradigm of
      Ca2+ signaling in the tongue.

PMID- 15556617
TI  - Capped acyclic permutants of the circular protein kalata B1.
AB  - The cyclotides are a family of head-to-tail cyclized peptides that display
      exceptionally high stability and a range of biological activities. Acyclic
      permutants that contain a break in the circular backbone have been reported to be
      devoid of the haemolytic activity of the prototypic cyclotide kalata B1, but the
      potential role of the charges at the introduced termini in this loss of
      membraneolytic activity has not been fully determined. In this study, acyclic
      permutants of kalata B1 with capped N- and C-termini were synthesized and found
      to adopt a native fold. These variants were observed to cause no measurable lysis
      of erythrocytes, strengthening the connection between backbone cyclization and
      haemolytic activity.

PMID- 15556618
TI  - The N-terminal rhodanese domain from Azotobacter vinelandii has a stable and
      folded structure independently of the C-terminal domain.
AB  - Sulfurtransferase are enzymes involved in the formation, conversion and transport
      of compounds containing sulfane-sulfur atoms. Although the three-dimensional
      structure of the rhodanese from the nitrogen-fixing bacterium Azotobacter
      vinelandii is known, the role of its two domains in the protein conformational
      stability is still obscure. We have evaluated the susceptibility to proteolytic
      degradation of the two domains of the enzyme. The two domains show different
      resistance to the endoproteinases and, in particular, the N-terminal domain shows
      to be more stable to digestion during time than the C-terminal one. Cloning and
      overexpression of the N-terminal domain of the protein was performed to better
      understand its functional and structural role. The recombinant N-terminal domain
      of rhodanese A. vinelandii is soluble in water solution and the spectroscopic
      studies by circular dichroism and heteronuclear NMR spectroscopy indicate a
      stable fold of the protein with the expected alpha/beta topology. The results
      indicate that this N-terminal domain has already got all the elements necessary
      for an C-terminal domain independent folding. Its solution structure by NMR,
      actually under course, will be a valid contribution to understand the role of
      this domain in the folding process of the sulfurtransferase.

PMID- 15556619
TI  - Phorbol ester-induced differentiation of L6 myogenic cells involves phospholipase
      D activation.
AB  - TPA, a potent PKC activator, inhibits myogenic differentiation and activates
      phospholipase D (PLD). We evaluated the involvement of PLD in the TPA effects on
      L6 myoblasts differentiation. TPA, at concentrations inhibiting differentiation
      of L6 cells, induced a strong, though transient, PLD activation. Surprisingly, at
      nanomolar concentration, TPA induced both myogenic differentiation and sustained
      activation of PLD. Differential effect of TPA can be ascribed to PKC
      downregulation induced by highest TPA concentrations. TPA-induced differentiation
      was inhibited by 1-butanol, confirming the involvement of PLD in this effect.
      These data suggest that prolonged elevation of PLD activity is required for
      myogenic differentiation.

PMID- 15556620
TI  - Structure-activity relationships of aminoglycoside-arginine conjugates that bind
      HIV-1 RNAs as determined by fluorescence and NMR spectroscopy.
AB  - We present here a new set of aminoglycoside-arginine conjugates (AACs) that are
      either site-specific or per-arginine conjugates of paromomycin, neamine, and
      neomycin B as well as their structure-activity relationships. Their binding
      constants (KD) for TAR and RRE RNAs, measured by fluorescence anisotropy,
      revealed dependence on the number and location of arginines in the different
      aminoglycoside conjugates. The binding affinity of the per-arginine
      aminoglycosides to TAR is higher than to RRE, and hexa-arginine neomycin B is the
      most potent binder (KD=5 and 23 nM, respectively). The 2D TOCSY NMR spectrum of
      the TAR monoarginine-neomycin complex reveals binding at the bulge region of TAR.

PMID- 15556621
TI  - A genome-wide screen identifies Yos9p as essential for ER-associated degradation
      of glycoproteins.
AB  - We undertook a growth-based screen exploiting the degradation of CTL*, a chimeric
      membrane-bound ERAD substrate derived from soluble lumenal CPY*. We screened the
      Saccharomyces cerevisiae genomic deletion library containing approximately 5000
      viable strains for mutants defective in endoplasmic reticulum (ER) protein
      quality control and degradation (ERAD). Among the new gene products we identified
      Yos9p, an ER-localized protein previously involved in the processing of GPI
      anchored proteins. We show that deficiency in Yos9p affects the degradation only
      of glycosylated ERAD substrates. Degradation of non-glycosylated substrates is
      not affected in cells lacking Yos9p. We propose that Yos9p is a lectin or lectin
      like protein involved in the quality control of N-glycosylated proteins. It may
      act sequentially or in concert with the ERAD lectin Htm1p/Mnl1p (EDEM) to prevent
      secretion of malfolded glycosylated proteins and deliver them to the cytosolic
      ubiquitin-proteasome machinery for elimination.

PMID- 15556622
TI  - Low doses of reactive oxygen species protect endothelial cells from apoptosis by
      increasing thioredoxin-1 expression.
AB  - The redox regulator thioredoxin-1 (Trx-1) is required for the redox potential of
      the cell and exerts important functions in cell growth and apoptosis. Severe
      oxidative stress has been implicated in the oxidation of proteins and cell death.
      However, the role of low doses of reactive oxygen species (ROS) is poorly
      understood. Here, we show that 10 and 50 microM H2O2 and short-term exposure to
      shear stress significantly increased Trx-1 mRNA and protein levels in endothelial
      cells. Since it is known that Trx-1 exerts anti-apoptotic functions, we next
      investigated whether low doses of ROS can inhibit basal and serum-depletion
      induced endothelial cell apoptosis. Indeed, treatment of endothelial cells with
      10 and 50 microM H2O2 significantly reduced apoptosis induction. Reduction of Trx
      1 expression using an antisense oligonucleotide approach resulted in the
      induction of apoptosis and abolished the inhibitory effect of low doses of H2O2.
      Taken together, our results demonstrate that low doses of ROS act as signaling
      molecules and exert anti-apoptotic functions in endothelial cells via
      upregulation of the redox-regulator Trx-1.

PMID- 15556623
TI  - The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity
      in an oxygen tension-dependent manner.
AB  - Hypoxia elicits a wide range of responses that occur at different organizational
      levels in the body. Hypoxia is not only a signal for energy conservation and
      metabolic change, but triggers expression of a select set of genes. The
      transcription factor hypoxia-inducible factor 1 (HIF-1) is now appreciated to be
      a master factor of the gene induction. Although knowledge on molecular mechanisms
      of HIF-1 activation in response to hypoxia is accumulating, the molecular
      mechanism of maintenance of HIF-1 activity under normoxic conditions remains to
      be elucidated. We demonstrate that the intravenous anesthetic propofol reversibly
      inhibits HIF-1 activity and the gene expression mediated by HIF-1 by blocking the
      synthesis of the HIF-1alpha subunit under 20% or 5% O2 conditions, but not under
      1% O2 conditions.

PMID- 15556624
TI  - Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to
      acidify extracellular pH.
AB  - Acidic extracellular pH (pHe) is a typical attribute of a tumor microenvironment,
      which has an impact on cancer development and treatment outcome. It was believed
      to result from an accumulation of lactic acid excessively produced by glycolysis.
      However, metabolic profiles of glycolysis-impaired tumors have revealed that CO2
      is a significant source of acidity, thereby indicating a contribution of carbonic
      anhydrase (CA). The tumor-associated CA IX isoform is the best candidate, because
      its extracellular enzyme domain is highly active, expression is induced by
      hypoxia and correlates with poor prognosis. This study provides the first
      evidence for the role of CA IX in the control of pHe. We show that CA IX can
      acidify the pH of the culture medium in hypoxia but not in normoxia. This
      acidification can be perturbed by deletion of the enzyme active site and
      inhibited by CA IX-selective sulfonamides, which bind only to hypoxic cells
      containing CA IX. Our findings suggest that hypoxia regulates both expression and
      activity of CA IX in order to enhance the extracellular acidification, which may
      have important implications for tumor progression.

PMID- 15556625
TI  - Stratum corneum-derived caspase-14 is catalytically active.
AB  - Caspase-14, a cysteine protease with restricted tissue distribution, is highly
      expressed in differentiated epidermal keratinocytes. Here, we extracted soluble
      proteins from stratum corneum (SC) of human epidermis and demonstrate that the
      extract cleaves tetrapeptide caspase substrates. The activity decreased to below
      10% when caspase-14 was removed by immunodepletion showing that caspase-14 is the
      predominant caspase in SC. In contrast to normal SC, where caspase-14 was present
      exclusively in its processed form, incompletely matured SC of parakeratotic skin
      from psoriasis and seborrheic dermatitis contained both procaspase-14 and caspase
      14 subunits. Fractionation of extract from parakeratotic SC revealed that the
      peak caspase activity coeluted with processed caspase-14 but not with procaspase
      14. Our results suggest that during regular terminal keratinocyte
      differentiation, endogenous procaspase-14 is converted to caspase-14 subunits
      that are catalytically active in the outermost layers of normal human skin.

PMID- 15556626
TI  - Vitamin D3 inhibits fatty acid synthase expression by stimulating the expression
      of long-chain fatty-acid-CoA ligase 3 in prostate cancer cells.
AB  - FAS and FACL3 are enzymes of fatty acid metabolism. In our previous studies, we
      found that FAS and FACL3 genes were vitamin D3-regulated and involved in the
      antiproliferative effect of 1alpha,25(OH)2D3 in the human prostate cancer LNCaP
      cells. Here, we elucidated the mechanism behind the downregulation of FAS
      expression by vitamin D3. Triacsin C, an inhibitor of FACL3 activity, completely
      abolished the downregulation of FAS expression by vitamin D3, whereas an
      inhibitor of FAS activity, cerulenin, had no significant effect on the
      upregulation of FACL3 expression by vitamin D3 in LNCaP cells. In human prostate
      cancer PC3 cells, in which FACL3 expression is not regulated by vitamin D3, no
      regulation of FAS expression was seen. This suggests that the downregulation of
      FAS expression by vitamin D3 is mediated by vitamin D3 upregulation of FACL3
      expression. Myristic acid, one of the substrates preferential for FACL3, enhanced
      the repression of FAS expression by vitamin D3. The action of myristic acid was
      abrogated by inhibition of FACL3 activity, suggesting that the enhancement in the
      downregulation of FAS expression by vitamin D3 is due to the formation of
      myristoyl-CoA. The data suggest that vitamin D3-repression of FAS mRNA expression
      is the consequence of feedback inhibition of FAS expression by long chain fatty
      acyl-CoAs, which are formed by FACL3 during its upregulation by vitamin D3 in
      human prostate cancer LNCaP cells.

PMID- 15556627
TI  - Militarinone A induces differentiation in PC12 cells via MAP and Akt kinase
      signal transduction pathways.
AB  - The fungal metabolite militarinone A (MILI A) promotes neurite outgrowth in PC12
      cells. This study was conducted to investigate the signaling pathways involved in
      the cellular differentiation processes induced by the compound, with a focus on
      cascades implicated with nerve growth factor (NGF)-mediated neuritogenesis. MILI
      A possessed pronounced amphiphilic properties. The compound rapidly accumulated
      in the cell membrane and was slowly released into the cytoplasma. In primed PC12
      cells, an early activation of protein kinase B (Akt), representing a downstream
      target of phosphoinositol 3 (PI3) kinase, and a delayed phosphorylation of
      extracellular signal-regulated kinases 1 and 2 (ERK1/2), and of transcription
      factor cAMP responsive element binding protein (CREB) was found. The NGF
      dependent activation of c-Jun amino terminal kinase (SAPK/JNK1) was potentiated.
      Morphological differentiation of cells and the phosphorylation of specific signal
      molecules were blocked by the MAP kinase (MEK1) inhibitor PD098059, the PI3
      kinase (PI3K) inhibitor wortmannin and the adenylyl cyclase inhibitor 9
      cyclopentyladenine.

PMID- 15556628
TI  - The Bacillus subtilis DnaD protein: a putative link between DNA remodeling and
      initiation of DNA replication.
AB  - The Bacillus subtilis DnaD protein is an essential protein and a component of the
      oriC and PriA primosomal cascades, which are responsible for loading the main
      replicative ring helicase DnaC onto DNA. We present evidence that DnaD also has a
      global DNA architectural activity, assembling into large nucleoprotein complexes
      on a plasmid and counteracting plasmid compaction in a manner analogous to that
      recently seen for the histone-like Escherichia coli HU proteins. This DNA
      remodeling role may be an essential function for initiation of DNA replication in
      the Gram +ve B. subtilis, thus highlighting DnaD as the link between bacterial
      nucleoid reorganization and initiation of DNA replication.

PMID- 15556629
TI  - Thermodynamics of apocalmodulin and nitric oxide synthase II peptide interaction.
AB  - The Ca2+-free form of calmodulin (CaM), apocalmodulin (ApoCaM), regulates a
      variety of target proteins including nitric oxide synthase II (NOS-II). The CaM
      binding site of NOS-II can bind ApoCaM with high affinity. Substitution of
      hydrophobic amino acids by charged amino acids at crucial positions 3, 9 and 13
      within the CaM-binding motif did not abolish the ApoCaM interaction that occurred
      with significant affinity, though the affinity of the interaction was decreased
      remarkably. Isothermal titration calorimetry revealed that interaction of ApoCaM
      and synthetic NOS-II peptides was driven entropically.

PMID- 15556630
TI  - Identification of enzymes acting on alpha-glycated amino acids in Bacillus
      subtilis.
AB  - We have characterized the Bacillus subtilis homologs of fructoselysine 6-kinase
      and fructoselysine-6-phosphate deglycase, two enzymes that specifically
      metabolize the Amadori compound fructose-epsilon-lysine in Escherichia coli. The
      B. subtilis enzymes also catalyzed the phosphorylation of fructosamines to
      fructosamine 6-phosphates (YurL) and the conversion of the latter to glucose 6
      phosphate and a free amino acid (YurP). However, their specificity was totally
      different from that of the E. coli enzymes, since they acted on fructoseglycine,
      fructosevaline (YurL) or their 6-phosphoderivatives (YurP) with more than 30-fold
      higher catalytic efficiencies than on fructose-alpha-lysine (6-phosphate). These
      enzymes are therefore involved in the metabolism of alpha-glycated amino acids.

PMID- 15556631
TI  - RNA interference-induced reduction in CD98 expression suppresses cell fusion
      during syncytialization of human placental BeWo cells.
AB  - The physiological importance of CD98 surface antigen in regulating placental
      trophoblast cell fusion has been studied in a cell model of syncytialization (the
      cytotrophoblast cell line BeWo following increased intracellular cAMP by
      forskolin treatment) using RNA interference. CD98 protein abundance (determined
      by Western blot) was decreased by 40-50% following double-stranded small
      interfering RNA transfection. Cell fusion (determined by quantitative flow
      cytometry) was similarly inhibited and human chorionic gonadotropin secretion was
      suppressed. These findings show that CD98 is involved in the process of cell
      fusion necessary for syncytiotrophoblast formation.

PMID- 15556632
TI  - Structural determinants of the selectivity of KTS-disintegrins for the
      alpha1beta1 integrin.
AB  - KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent
      and selective inhibitors of alpha1beta1 integrin. The amino acid sequence of the
      new KTS-disintegrin, viperistatin, differs from previously characterized
      obtustatin in three residues at position 24 (within the integrin binding loop),
      38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is
      about 25-fold more potent than obtustatin inhibiting the binding of this integrin
      to collagen IV. Synthetic peptides representing the full-length of integrin
      binding loops of these disintegrins showed that the Leu24/Arg substitution
      appears to be partly responsible for the increased inhibitory activity of
      viperistatin over obtustatin.

PMID- 15556633
TI  - Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in
      both male and female rats.
AB  - We investigated in vivo the chemotherapeutic anthracycline agents doxorubicin and
      its ability to activate mitochondrial-mediated, receptor-mediated and
      endoplasmic/sarcoplasmic reticulum-mediated apoptosis transduction pathways in
      cardiac tissue from male and female rats. We administered a single low dose of
      doxorubicin (10 mg/kg of body weight, i.p.) and then isolated mitochondrial and
      cytosolic proteins one and four days later from the heart. Caspase-3 protein
      content and caspase-3 activity were significantly increased after day four of
      doxorubicin treatment in both male and female rats. However, while males had DNA
      fragmentation at day one but not day four following doxorubicin administration,
      females showed no significant increase in DNA fragmentation at either time.
      Caspase-12, localized in the SR, is considered a central caspase, and its
      activation by cleavage via calpain indicates activation of the SR-mediated
      pathway of apoptosis. Cleaved caspase-12 content and calpain activity
      significantly increased after day four of doxorubicin treatment in both sexes. In
      the mitochondrial-mediated pathway, there were no significant treatment effects
      observed in cytosolic cytochrome c and cleaved (active) caspase-9 in either sex.
      In control rats (saline injection), glutathione peroxidase (GPX) activity and
      hydrogen peroxide (H2O2) production were lower in females compared to males.
      Doxorubicin treatment did not significantly affect H2O2, GPX activity or ATP
      production in isolated mitochondria in either sex. Female rats produced
      significantly lower levels of H2O2 production one day after doxorubicin
      treatment, whereas male rats produced significantly less mitochondrial H2O2 four
      days after doxorubicin treatment. The receptor-mediated pathway (caspase-8 and c
      FLIP) showed no evidence of being significantly activated by doxorubicin
      treatment. Hence, doxorubicin-induced apoptosis in vivo is mediated by the SR to
      a greater extent than other apoptotic pathways and should therefore be considered
      for targeted therapeutic interventions. Moreover, no major sex differences exist
      in apoptosis signaling transduction cascade due to doxorubicin treatment.

PMID- 15556634
TI  - Atg21p is essential for macropexophagy and microautophagy in the yeast Hansenula
      polymorpha.
AB  - ATG genes are required for autophagy-related processes that transport
      proteins/organelles destined for proteolytic degradation to the vacuole. Here, we
      describe the identification and characterisation of the Hansenula polymorpha
      ATG21 gene. Its gene product Hp-Atg21p, fused to eGFP, had a dual location in the
      cytosol and in peri-vacuolar dots. We demonstrate that Hp-Atg21p is essential for
      two separate modes of peroxisome degradation, namely glucose-induced
      macropexophagy and nitrogen limitation-induced microautophagy. In atg21 cells
      subjected to macropexophagy conditions, sequestration of peroxisomes tagged for
      degradation is initiated but fails to complete.

PMID- 15556635
TI  - Prothymosin alpha associates with the oncoprotein SET and is involved in
      chromatin decondensation.
AB  - Prothymosin alpha (ProTalpha) is a histone H1-binding protein that interacts with
      the transcription coactivator CREB-binding protein and potentiates transcription.
      Based on coimmunoprecipitation and mammalian two-hybrid assays, we show here that
      ProTalpha forms a complex with the oncoprotein SET. ProTalpha efficiently
      decondenses human sperm chromatin, while overexpression of GFP-ProTalpha in
      mammalian cells results in global chromatin decondensation. These results
      indicate that decondensation of compacted chromatin fibers is an important step
      in the mechanism of ProTalpha function.

PMID- 15556636
TI  - S-adenosyl-L-homocysteine hydrolase in yeast: key enzyme of methylation
      metabolism and coordinated regulation with phospholipid synthesis.
AB  - S-adenosyl-L-homocysteine hydrolase (Sah1p, EC 3.3.1.1.) is a key enzyme of
      methylation metabolism. It catabolizes S-adenosyl-L-homocysteine, which is formed
      after donation of the activated methyl group of S-adenosyl-L-methionine (AdoMet)
      to an acceptor, and which acts as strong competitive inhibitor of all AdoMet
      dependent methyltransferases. Sah1p is an essential enzyme in yeast and one of
      the most highly conserved proteins with up to 80% sequence homology throughout
      all kingdoms of life. SAH1 expression in yeast is subject to the general
      transcriptional control of phospholipid synthesis. Profound changes in cellular
      lipid composition upon depletion of Sah1p support the notion of a tight
      interaction between lipid metabolism and Sah1p function.

PMID- 15556637
TI  - Tetrahydrobiopterin protects phenylalanine hydroxylase activity in vivo:
      implications for tetrahydrobiopterin-responsive hyperphenylalaninemia.
AB  - The natural cofactor of phenylalanine hydroxylase (PAH), tetrahydrobiopterin
      (BH4), regulates the enzyme activity as well as being essential in catalysis. BH4
      responsive PAH deficiency is a variant of hyperphenylalaninemia or
      phenylketonuria (PKU) caused by mutations in the human PAH gene that respond to
      oral BH4 loading by stimulating enzyme activity and therefore lowering serum
      phenylalanine. Here, we showed in a coupled transcription-translation in vitro
      assay that upon expression in the presence of BH4, wild-type PAH enzyme activity
      was enhanced. We then investigated the effect of BH4 on PAH activity in
      transgenic mice that had a complete or partial deficiency in the endogenous
      cofactor biosynthesis. The rate of hepatic PAH enzyme activity increased
      significantly with BH4 content without affecting gene expression or Pah-mRNA
      stability. These results indicate that BH4 has a chaperon-like effect on PAH
      synthesis and/or is a protecting cofactor against enzyme auto-inactivation and
      degradation also in vivo. Our findings thus contribute to the understanding of
      the regulation of PAH by its cofactor BH4 on an additional level and provide a
      molecular explanation for cofactor-responsive PKU.

PMID- 15556638
TI  - Identification and characterization of a novel factor XIIa inhibitor in the
      hematophagous insect, Triatoma infestans (Hemiptera: Reduviidae).
AB  - Recently, we have cloned several Kazal-type serine protease inhibitors from the
      midgut of the Triatoma infestans bug. A single gene composed of multi Kazal-type
      domains, in tandem, encodes these inhibitors. In this work, we describe the
      purification and characterization of recombinant infestins 3-4 and 4, which are
      potent factor XIIa inhibitors (KI=67 pM and 128 pM, respectively). We also
      identified the first native factor XIIa inhibitor from a hematophagous insect.
      The factor XIIa inhibitory activity of infestin 4 demonstrates extremely
      efficient anticoagulant activity, prolonging activated partial thromboplastin
      time by approximately 3 times. Our results suggest that infestins perform a very
      important role in the T. infestans midgut during meal acquisition and digestion
      by controlling blood coagulation by means of inhibiting thrombin and factor XIIa.

PMID- 15556639
TI  - Catalytic RNase P RNA from Synechocystis sp. cleaves the hepatitis C virus RNA
      near the AUG start codon.
AB  - Previously, we described two RNA structural motifs in the hepatitis C viral (HCV)
      genome that can be processed in vitro by human ribonuclease P (RNase P) enzyme
      [J. Biol. Chem. 277 (2002) 30606]. One of these structures is located in the
      internal ribosome entry site and is conserved in the related animal pestiviruses
      [J. Biol. Chem. 278 (2003) 26844]. Here, we tested two prokaryotic RNase P
      ribozymes (P RNA) against this conserved structural motif. In vitro experiments
      indicated that P RNA from Synechocystis sp. can specifically process the viral
      transcript preparations in a position close to the human RNase P cleavage site.
      This provides additional support for the presence of an RNA structure similar to
      tRNA near the AUG start codon and suggests that Synechocystis P RNA may be an
      active agent for HCV antigenomic interventions.

PMID- 15556640
TI  - Discovery of the catalytic function of a putative 2-oxoacid dehydrogenase
      multienzyme complex in the thermophilic archaeon Thermoplasma acidophilum.
AB  - Those aerobic archaea whose genomes have been sequenced possess a single 4-gene
      operon that, by sequence comparisons with Bacteria and Eukarya, appears to encode
      the three component enzymes of a 2-oxoacid dehydrogenase multienzyme complex.
      However, no catalytic activity of any such complex has ever been detected in the
      Archaea. In the current paper, we have cloned and expressed the first two genes
      of this operon from the thermophilic archaeon, Thermoplasma acidophilum. We
      demonstrate that the protein products form an alpha2beta2 hetero-tetramer
      possessing the decarboxylase catalytic activity characteristic of the first
      component enzyme of a branched-chain 2-oxoacid dehydrogenase multienzyme complex.
      This represents the first report of the catalytic function of these putative
      archaeal multienzyme complexes.

PMID- 15556641
TI  - FRU (BHLH029) is required for induction of iron mobilization genes in Arabidopsis
      thaliana.
AB  - Iron mobilization responses are induced by low iron supply at transcriptional
      level. In tomato, the basic helix-loop-helix gene FER is required for induction
      of iron mobilization. Using molecular-genetic techniques, we analyzed the
      function of BHLH029, named FRU (FER-like regulator of iron uptake), the
      Arabidopsis thaliana homolog of the tomato FER gene. The FRU gene was mainly
      expressed in roots in a cell-specific pattern and induced by iron deficiency. FRU
      mutant plants were chlorotic, and the FRU gene was found necessary for induction
      of the essential iron mobilization genes FRO2 (ferric chelate reductase gene) and
      IRT1 (iron-regulated transporter gene). Overexpression of FRU resulted in an
      increase of iron mobilization responses at low iron supply. Thus, the FRU gene is
      a mediator in induction of iron mobilization responses in Arabidopsis, indicating
      that regulation of iron uptake is conserved in dicot species.

PMID- 15556642
TI  - Substitutional editing of transcripts from genes of cyanobacterial origin in the
      dinoflagellate Ceratium horridum.
AB  - Peridinin-containing dinoflagellates, a group of alveolate organisms, harbour
      small plasmids called minicircles. As most of these minicircles encode genes of
      cyanobacterial origin, which are also found in plastid genomes of stramenopiles,
      they were thought to represent the plastid genome of peridinin-containing
      dinoflagellates. The analyses of minicircle derived mRNAs and the 16S rRNA showed
      that extensive editing of minicircle gene transcripts is common for Ceratium
      horridum. Posttranscriptional changes occur predominantly by editing A into G,
      but other types of editing including a previously unreported A to C transversion
      were also detected. This leads to amino acid changes in most cases or, in one
      case, to the elimination of a stop-codon. Interestingly, the edited mRNAs show
      higher identities to homologous sequences of other peridinin-containing
      dinoflagellates than their genomic copy. Thus, our results imply that transcript
      editing of genes of cyanobacterial origin is species specific in peridinin
      containing dinoflagellates and demonstrate that editing of genes of
      cyanobacterial origin is not restricted to land plants.

PMID- 15556643
TI  - The direct effect of leptin on skeletal muscle thermogenesis is mediated by
      substrate cycling between de novo lipogenesis and lipid oxidation.
AB  - We report here studies that integrate data of respiration rate from mouse
      skeletal muscle in response to leptin and pharmacological interference with
      intermediary metabolism, together with assays for phosphatidylinositol 3-kinase
      (PI3K) and AMP-activated protein kinase (AMPK). Our results suggest that the
      direct effect of leptin in stimulating thermogenesis in skeletal muscle is
      mediated by substrate cycling between de novo lipogenesis and lipid oxidation,
      and that this cycle requires both PI3K and AMPK signaling. This substrate cycling
      linking glucose and lipid metabolism to thermogenesis provides a novel
      thermogenic mechanism by which leptin protects skeletal muscle from excessive fat
      storage and lipotoxicity.

PMID- 15556644
TI  - A multicystatin is induced by drought-stress in cowpea (Vigna unguiculata (L.)
      Walp.) leaves.
AB  - Cystatins are protein inhibitors of cystein proteinases belonging to the papain
      family. In cowpea, cystatin-like polypeptides and a cDNA have been identified
      from seeds and metabolic functions have been attributed to them. This paper
      describes VuC1, a new cystatin cDNA isolated from cowpea leaves (Vigna
      unguiculata (L.) Walp.). Sequence analysis revealed a multicystatin structure
      with two cystatin-like domains. The recombinant VUC1 protein (rVUC1) was
      expressed in an heterologous expression system and purified to apparent
      homogeneity. It appeared to be an efficient inhibitor of papain activity on a
      chromogenic substrate. Polyclonal antibodies against rVUC1 were obtained.
      Involvement of the VuC1 cDNA in the cellular response to various abiotic stresses
      (progressive drought-stress, dessication and application of exogenous abscissic
      acid) was studied, using Northern blot and Western blot analysis, in the leaf
      tissues of cowpea plants corresponding to two cultivars with different capacity
      to tolerate drought-stress. Surprisingly, these abiotic stresses induced
      accumulation of two VuC1-like messages both translated into VUC1-like
      polypeptides. Difference in the transcript accumulation patterns was observed
      between the two cultivars and related to their respective tolerance level.
      Presence of multiple cystatin-like polypeptides and their possible involvement in
      the control of leaf protein degradation by cysteine proteinases is discussed.

PMID- 15556645
TI  - The role of bestrophin in airway epithelial ion transport.
AB  - The purpose of this study was to identify Cl- channels in the basolateral
      membrane of airway epithelial cells at the molecular level. We have focused on a
      new family of Cl- channels, bestrophins, which have previously been identified in
      retinal pigment epithelium. RT-PCR, Western blot and confocal microscopy studies
      revealed the presence of bestrophin in airway epithelial cells. Decreasing
      bestrophin expression using siRNA resulted in diminished 36Cl- flux. These
      studies also showed that bestrophin regulation is similar to that of native
      basolateral Cl- channels. The data indicate that the presence of a functional
      bestrophin may contribute to the basolateral cell conductance in airway
      epithelial cells.

PMID- 15556646
TI  - Catalytic domains of tyrosine kinases determine the phosphorylation sites within
      c-Cbl.
AB  - Catalytic (SH1) domains of protein tyrosine kinases (PTKs) demonstrate
      specificity for peptide substrates. Whether SH1 domains differentiate between
      tyrosines in a physiological substrate has not been confirmed. Using purified
      proteins, we studied the ability of Syk, Fyn, and Abl to differentiate between
      tyrosines in a common PTK substrate, c-Cbl. We found that each kinase produced a
      distinct pattern of c-Cbl phosphorylation, which altered the phosphotyrosine
      dependent interactions between c-Cbl and CrkL or phosphatidylinositol 3'-kinase
      (PI3-K). Our data support the concept that SH1 domains determine the final sites
      of phosphorylation once PTKs reach their target proteins.

PMID- 15556647
TI  - Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor
      CB2 and multiple signal transduction pathways.
AB  - Echinacea plant preparations are widely used in the prevention and treatment of
      common cold. However, so far no molecular mechanism of action has been proposed.
      We analyzed the standardized tincture Echinaforce and found that it induced de
      novo synthesis of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human
      monocytes/macrophages, but not TNF-alpha protein. Moreover, LPS-stimulated TNF
      alpha protein was potently inhibited in the early phase but prolonged in the late
      phase. A study of the main constituents of the extract showed that the
      alkylamides dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (1/2), trienoic
      (3) and dienoic acid (4) derivatives are responsible for this effect. The
      upregulation of TNF-alpha mRNA was found to be mediated by CB2 receptors,
      increased cAMP, p38/MAPK and JNK signaling, as well as NF-kappaB and ATF-2/CREB-1
      activation. This study is the first to report a possible molecular mechanism of
      action of Echinacea, highlighting the role of alkylamides as potent
      immunomodulators and potential ligands for CB2 receptors.

PMID- 15556648
TI  - Measurement of velocity variations along a wave path in the through-thickness
      direction in a plate.
AB  - In this paper there is given a method to predict ultrasonic wave velocity
      variations along a wave path in the through-thickness direction in a plate from
      thickness resonance spectra. Thickness resonance spectra are numerically
      calculated and two simple rules used to predict the entire ultrasonic wave
      velocity variation are derived. In the calculation, the wave path is assumed to
      be straight along the thickness direction and the velocity variation is assumed
      to be either as a parabolic curve dependence or a linear dependence with respect
      to the distance from the surface and to be symmetric with respect to the plate
      center. To see if the numerical calculation method is reliable, thickness
      resonance frequencies of a sample with three-layers were measured by EMAT
      (electromagnetic acoustic transducer) with a good agreement between the measured
      and the calculated frequencies. This method can be applied to the ultrasonic
      measurement of material characteristics, internal stress or various other
      properties of plate materials.

PMID- 15556649
TI  - Boundary element simulation of backscattering properties for red blood with high
      frequency ultrasonic transducers.
AB  - High frequency ultrasonic imaging (e.g. >30 MHz) from blood is difficult due to
      its tenuous backscattered pressure and the interference from adjacent tissues as
      well. To increase the sensitivity focused transducer has to be used, thus raising
      the complexity of interpreting the received signals. A numerical simulation of
      the ultrasonic scattering property from erythrocyte and rouleaux based on
      boundary element method was performed with experimental results based on a
      modified substitution method. The results (proportional relationship between
      backscattered pressure and frequency and the frequency limit for Rayleigh
      scattering) closely coincide with experimental data for erythrocyte. Rouleaux
      model results also show the dependence of degree of red cell aggregation on
      backscattering properties. The boundary element method serves as a good means to
      calculate the acoustic scattering from blood cells under arbitrary incident
      waves.

PMID- 15556650
TI  - Development of a portable 3D ultrasound imaging system for musculoskeletal
      tissues.
AB  - 3D ultrasound is a promising imaging modality for clinical diagnosis and
      treatment monitoring. Its cost is relatively low in comparison with CT and MRI,
      no intensive training and radiation protection is required for its operation, and
      its hardware is movable and can potentially be portable. In this study, we
      developed a portable freehand 3D ultrasound imaging system for the assessment of
      musculoskeletal body parts. A portable ultrasound scanner was used to obtain real
      time B-mode ultrasound images of musculoskeletal tissues and an electromagnetic
      spatial sensor was fixed on the ultrasound probe to acquire the position and
      orientation of the images. The images were digitized with a video digitization
      device and displayed with its orientation and position synchronized in real-time
      with the data obtained by the spatial sensor. A program was developed for volume
      reconstruction, visualization, segmentation and measurement using Visual C++ and
      Visualization toolkits (VTK) software. A 2D Gaussian filter and a Median filter
      were implemented to improve the quality of the B-scan images collected by the
      portable ultrasound scanner. An improved distance-weighted grid-mapping algorithm
      was proposed for volume reconstruction. Temporal calibrations were conducted to
      correct the delay between the collections of images and spatial data. Spatial
      calibrations were performed using a cross-wire phantom. The system accuracy was
      validated by one cylinder and two cuboid phantoms made of silicone. The average
      errors for distance measurement in three orthogonal directions in comparison with
      micrometer measurement were 0.06+/-0.39, -0.27+/-0.27, and 0.33+/-0.39 mm,
      respectively. The average error for volume measurement was -0.18%+/-5.44% for the
      three phantoms. The system has been successfully used to obtain the volume images
      of a fetus phantom, the fingers and forearms of human subjects. For a typical
      volume with 126 x 103 x 109 voxels, the 3D image could be reconstructed from 258
      B-scans (640 x 480 pixels) within one minute using a portable PC with Pentium IV
      2.4 GHz CPU and 512 MB memories. It is believed that such a portable volume
      imaging system will have many applications in the assessment of musculoskeletal
      tissues because of its easy accessibility.

PMID- 15556651
TI  - Development of a multi frequency pulse diagnostic ultrasound device.
AB  - Diagnostic ultrasound is a powerful tool for characterising a wide range of
      solutions, with devices such as the continuous wave Malvern Ultrasizer at the
      forefront. However to reduce capital cost and allow online application without
      reducing accuracy and application a new system was designed, built and made
      operational. The ultrafood system is a variable path length pulse system, which
      produces both time and frequency domain data that is repeatable and accurate
      compared to reference methods and values. The use of multiple distance
      measurement removes the need for reference fluid calibration and thermal
      expansion compensation.

PMID- 15556652
TI  - Finite element modelling of dense and porous piezoceramic disc hydrophones.
AB  - The acoustic characteristics of dense and porous piezoceramic disc hydrophones
      have been studied by finite element modelling (FEM). The FEM results are
      validated initially by an analytical model for a simple disc of dense
      piezoceramic material and then it is extended to a porous piezoceramic disc
      replicating a foam-reticulated sample. Axisymmetric model was used for dense
      piezoceramic hydrophone due its regular geometric shape. 3-dimensional model was
      used for the porous piezoceramics, since the unit cell model is inadequate to
      fully represent transducers of finite lateral dimensions. The porous PZT discs
      have been synthesised by foam-reticulation technique. The electrical impedance
      and the receiving sensitivity of the hydrophones in water are evaluated in the
      frequency range 10-100 kHz. The model results are compared with the experimental
      data. The receiving sensitivity of piezocomposite hydrophones is found to be
      reasonably constant over the frequency range studied. The sharp resonance peaks
      observed for the dense piezoceramic hydrophone has broadened to a large extent
      for porous piezoceramic hydrophones, indicating higher losses. The flat frequency
      response suggests that the 3-3 piezocomposites are useful for wide-band
      hydrophone applications.

PMID- 15556653
TI  - The radiated fields of focussing air-coupled ultrasonic phased arrays.
AB  - This paper presents an investigation into the fields radiated into air by
      ultrasonic phased arrays under transient excitation. In particular, it includes a
      theoretical prediction of spatial variations in amplitude throughout the both the
      near-field and far-field of such arrays. The approach has been used to predict
      the result of phasing to produce a focus in air, which can be seen to be
      particularly effective in the near-field of the array. Interesting features are
      observed, which are then described in terms of the performance of both individual
      elements and the resulting array. It is shown how some elements of design can be
      used to improve performance in focussing. The predictions are compared to the
      results of experiments in air using electrostatic arrays, where good focussing
      could be achieved provided the appropriate design principles were followed. The
      approach has been developed specifically for use in air, but the results would
      also hold for modelling in certain medical arrays where a focussing requirement
      might be needed close to the array itself.

PMID- 15556654
TI  - A semi-analytical model for predicting multiple propagating axially symmetric
      modes in cylindrical waveguides.
AB  - A semi-analytical model for multiple mode axially symmetric wave propagation in
      finite solid cylindrical waveguides is presented. The model is designed as a tool
      for predicting and interpreting experimental signals. The model is based on a
      common experimental configuration and considers the excitation, propagation and
      reception of the ultrasonic signal in the waveguide. The Pochhammer-Chree
      solution for an infinite cylinder is the basis for the model. Extensions are made
      to enable comparison to experimental results. Comparisons with experiment are
      performed in the time, frequency and joint-time frequency domain for both narrow
      band and broad band excitation of the piezo-electric transducer.

PMID- 15556656
TI  - More research is needed to determine the safety of static magnetic fields.

PMID- 15556657
TI  - Present and future magnetic resonance sources of exposure to static fields.
AB  - This paper considers the exposure of humans to static magnetic fields due to
      magnetic resonance imaging (MRI) procedures. It briefly introduces the types of
      magnetic fields associated with MRI. It then discusses trends in the number of
      people exposed to MRI, the field strength of the magnets used in MRI, and the
      types of applications of MRI. It also considers the types of staff who are
      exposed to magnetic fields due to MRI, and the alternative techniques that would
      be used in the absence of MRI.

PMID- 15556658
TI  - Physical interactions of static magnetic fields with living tissues.
AB  - Clinical magnetic resonance imaging (MRI) was introduced in the early 1980s and
      has become a widely accepted and heavily utilized medical technology. This
      technique requires that the patients being studied be exposed to an intense
      magnetic field of a strength not previously encountered on a wide scale by
      humans. Nonetheless, the technique has proved to be very safe and the vast
      majority of the scans have been performed without any evidence of injury to the
      patient. In this article the history of proposed interactions of magnetic fields
      with human tissues is briefly reviewed and the predictions of electromagnetic
      theory on the nature and strength of these interactions are described. The
      physical basis of the relative weakness of these interactions is attributed to
      the very low magnetic susceptibility of human tissues and the lack of any
      substantial amount of ferromagnetic material normally occurring in these tissues.
      The presence of ferromagnetic foreign bodies within patients, or in the vicinity
      of the scanner, represents a very great hazard that must be scrupulously avoided.
      As technology and experience advance, ever stronger magnetic field strengths are
      being brought into service to improve the capabilities of this imaging technology
      and the benefits to patients. It is imperative that vigilance be maintained as
      these higher field strengths are introduced into clinical practice to assure that
      the high degree of patient safety that has been associated with MRI is
      maintained.

PMID- 15556659
TI  - Rapporteur's report: sources and interaction mechanisms.
AB  - This, the first session of the Workshop, focussed on sources of exposure to and
      interaction mechanisms of intense static magnetic fields. The four presentations
      dealt with (1) the magnetic fields produced by diagnostic magnetic resonance
      imaging systems; (2) the ways in which static magnetic fields can interact with
      matter, in particular human tissue; (3) the effects of magnetic fields on enzyme
      reaction rates; and (4) working practices for high-field magnet development.

PMID- 15556660
TI  - Effects of static magnetic fields at the cellular level.
AB  - There have been few studies on the effects of static magnetic fields at the
      cellular level, compared to those of extremely low frequency magnetic fields.
      Past studies have shown that a static magnetic field alone does not have a lethal
      effect on the basic properties of cell growth and survival under normal culture
      conditions, regardless of the magnetic density. Most but not all studies have
      also suggested that a static magnetic field has no effect on changes in cell
      growth rate. It has also been shown that cell cycle distribution is not
      influenced by extremely strong static magnetic fields (up to a maximum of 10 T).
      A further area of interest is whether static magnetic fields cause DNA damage,
      which can be evaluated by determination of the frequency of micronucleus
      formation. The presence or absence of such micronuclei can confirm whether a
      particular treatment damages cellular DNA. This method has been used to confirm
      that a static magnetic field alone has no such effect. However, the frequency of
      micronucleus formation increases significantly when certain treatments (e.g., X
      irradiation) are given prior to exposure to a 10 T static magnetic field. It has
      also been reported that treatment with trace amounts of ferrous ions in the cell
      culture medium and exposure to a static magnetic field increases DNA damage,
      which is detected using the comet assay. In addition, many studies have found a
      strong magnetic field that can induce orientation phenomena in cell culture.

PMID- 15556661
TI  - Static magnetic fields: animal studies.
AB  - Various experimental studies carried out over the last 30-40 years have examined
      the effects of the chronic or acute exposure of laboratory animals to static
      magnetic fields. Many of the earlier studies have been adequately reviewed
      elsewhere; few adverse effects were identified. This review focuses on studies
      carried out more recently, mostly those using vertebrates, particularly mammals.
      Four main areas of investigation have been covered, viz., nervous system and
      behavioural studies, cardiovascular system responses, reproduction and
      development, and genotoxicity and cancer. Work on the role of the natural
      geomagnetic field in animal orientation and migration has been omitted.
      Generally, the acute responses found during exposure to static fields above about
      4 T are consistent with those found in volunteer studies, namely the induction of
      flow potentials around the heart and the development of aversive/avoidance
      behaviour resulting from body movement in such fields. No consistently
      demonstrable effects of exposure to fields of approximately 1T and above have
      been seen on other behavioural or cardiovascular endpoints. In addition, no
      adverse effects of such fields on reproduction and development or on the growth
      and development of tumours have been firmly established. Overall, however, far
      too few animal studies have been carried out to reach any firm conclusions.

PMID- 15556662
TI  - Health effects of static magnetic fields--a review of the epidemiological
      evidence.
AB  - Potential health effects of static magnetic fields have received far less
      attention than, for example, power frequency or radiofrequency fields. Static
      fields are found in certain occupational settings, e.g. in the aluminium and
      chloralkali industries, in arc-welding processes, and certain railways systems.
      Magnetic resonance imaging (MRI) for medical diagnosis is another source. This
      paper summarizes the epidemiological evidence of static magnetic field exposure
      and long-term health effects. There are only a few epidemiological studies
      available, and the majority of these have focused on cancer risks. There are some
      reports on reproductive outcomes, and sporadic studies of other outcomes.
      Overall, few occupational studies have focused specifically on effects of static
      magnetic field exposure, and exposure assessment have consequently been poor or
      non-existent. Results from studies that have estimated static magnetic field
      exposure have not indicated any increased cancer risks, but they are generally
      based on small numbers of cases and crude exposure assessment. Control of
      confounding has been limited, and it is likely that the "healthy worker" effect
      have influenced the results. A few studies have reported results on reproductive
      outcomes among aluminium workers and MRI operators, but limitations in study
      designs prevent conclusions. A problem in epidemiological studies of static
      magnetic fields is that workers in exposed occupations are also exposed to a wide
      variety of other potentially harmful agents, including some known carcinogens. In
      conclusion, the available evidence from epidemiological studies is not sufficient
      to draw any conclusions about potential health effects of static magnetic field
      exposure.

PMID- 15556663
TI  - Rapporteur report: cellular, animal and epidemiological studies of the effects of
      static magnetic fields relevant to human health.
AB  - Three talks were presented in the session on "Cellular, Animal and
      Epidemiological Studies of the Effects of Static Magnetic Fields Relevant to
      Human Health". The first talk presented the in vitro effects of static magnetic
      fields on cell cultures. The second talk presented the in vivo evidence obtained
      from animal studies. The final, third talk, presented the evidence obtained from
      epidemiological studies. The overall conclusion of the three presentations and
      the following general discussion was that the scientific evidence available to
      date is weak and contains large gaps in knowledge either due to the poor quality
      of published studies or because of the lack of published research on certain
      health-related topics. It was emphasized that the rapid development of new
      technological applications of static magnetic fields (e.g. magnetic levitation
      trains or magnetic resonance imaging-MRI) results in the human population at
      large, in certain occupations, and in a selected population of clinical patients
      being exposed to ever increasing static magnetic field strengths. It is of
      concern that the knowledge presently available concerning the health effects of
      these strong static magnetic fields is lagging a long way behind technological
      development. In conclusion, it was suggested that there is an urgent need to
      perform new studies in all research areas (in vitro, in vivo and epidemiology) in
      order to fill the present gaps in knowledge and provide assurance that this
      technology will not cause any unwanted and unexpected health side effects.

PMID- 15556664
TI  - Static magnetic field effects on human subjects related to magnetic resonance
      imaging systems.
AB  - GOAL: This paper reviews recent studies evaluating human subjects for physiologic
      or neuro-cognitive function adverse effects resulting from exposure to static
      magnetic fields of magnetic resonance imaging systems. MATERIALS AND METHODS: The
      results of three studies are summarized. Two studies evaluated exposure to a
      maximum of 8 Tesla (T). The first series studied 25 normal human subjects'
      sequential vital signs (heart rate, blood pressure, blood oxygenation, core
      temperature, ECG, respiratory rate) measured at different magnetic field
      strengths to a maximum of 8 T. A second series of 25 subjects were studied at
      0.05 and 8 T (out and in the bore of the magnet), performing 12 different
      standardized neuro-psychological tests and auditory-motor reaction times. The
      subjects' comments were recorded immediately following the study and after a
      three-month interval. The third study contained 17 subjects, placed near the bore
      of a 1.5 T magnet, and it used six different cognitive, cognitive-motor, or
      sensory tests. RESULTS: There were no clinically significant changes in the
      subjects' physiologic measurements at 8 T. There was a slight increase in the
      systolic blood pressure with increasing magnetic field strength. There did not
      appear to be any adverse effect on the cognitive performance of the subjects at 8
      T. A few subjects commented at the time of initial exposure on dizziness,
      metallic taste in the mouth, or discomfort related to the measurement instruments
      or the head coil. There were no adverse comments at 3 months. The 1.5 T study had
      two of the four neuro-behavioral domains exhibiting adverse effects (sensory and
      cognitive-motor). CONCLUSIONS: These studies did not demonstrate any clinically
      relevant adverse effects on neuro-cognitive testing or vital sign changes. One
      short-term memory, one sensory, and one cognitive-motor test demonstrated adverse
      effects, but the significance is not clear.

PMID- 15556665
TI  - Numerical evaluation of the fields induced by body motion in or near high-field
      MRI scanners.
AB  - In modern magnetic resonance imaging , both patients and health care workers are
      exposed to strong, non-uniform static magnetic fields inside and outside of the
      scanner, in which body movement may be able to induce electric currents in
      tissues which could be potentially harmful. This paper presents theoretical
      investigations into the spatial distribution of induced E-fields in a tissue
      equivalent human model when moving at various positions around the magnet. The
      numerical calculations are based on an efficient, quasi-static, finite-difference
      scheme. Three-dimensional field profiles from an actively shielded 4 T magnet
      system are used and the body model projected through the field profile with
      normalized velocity. The simulation shows that it is possible to induce E
      fields/currents near the level of physiological significance under some
      circumstances and provides insight into the spatial characteristics of the
      induced fields. The methodology presented herein can be extrapolated to very high
      field strengths for the evaluation of the effects of motion at a variety of field
      strengths and velocities.

PMID- 15556666
TI  - Magnetically induced electric fields and currents in the circulatory system.
AB  - Blood flow in an applied magnetic field gives rise to induced voltages in the
      aorta and other major arteries of the central circulatory system that can be
      observed as superimposed electrical signals in the electrocardiogram (ECG). The
      largest magnetically induced voltage occurs during pulsatile blood flow into the
      aorta, and results in an increased signal at the location of the T-wave in the
      ECG. Studies involving the measurement of blood pressure, blood flow rate, heart
      sounds, and cardiac valve displacements have been conducted with monkeys and dogs
      exposed to static fields up to 1.5 tesla (T) under conditions producing maximum
      induced voltages in the aorta. Results of these studies gave no indication of
      alterations in cardiac functions or hemodynamic parameters. Cardiac activity
      monitored by ECG biotelemetry during continuous exposure of rats to a 1.5-T field
      for 10 days gave no evidence for any significant changes relative to the 10 days
      prior to and following exposure. Theoretical modeling of magnetic field
      interactions with blood flow has included a complete solution of the equation
      describing the flow of an electrically conductive fluid in the presence of a
      magnetic field (the Navier-Stokes equation) using the finite element technique.
      Magnetically induced voltages and current densities as a function of the applied
      magnetic field strength have been calculated for the aorta and surrounding
      tissues structures, including the sinoatrial node. Induced current densities in
      the region of the sinoatrial node are predicted to be >100 mA/m2 at field levels
      >5 T in an adult human under conditions of maximum electrodynamic coupling with
      aortic blood flow. Magnetohydrodynamic interactions are predicted to reduce the
      volume flow rate of blood in the human aorta by a maximum of 1.3%, 4.9%, and
      10.4% at field levels of 5, 10, and 15 T, respectively.

PMID- 15556667
TI  - The sensitivity of the heart to static magnetic fields.
AB  - Static magnetic fields induce flow potentials in arterial flows in and around the
      heart, that have been detected as distortions in the ECG. The resultant currents
      flowing through the myocardium could alter the rate or rhythm of the heart. No
      such changes have been seen in animal experiments, or with humans, in static
      fields up to 8 T. The possible effects of such currents induced by fields larger
      than 8 T on cardiac pacemaker rate, and arrhythmogenesis are reviewed, using
      virtual cardiac tissues-computational models of cardiac electrophysiology.
      Arrhythmogenesis can be by the initiation of ectopic beats, or by re-entry, whose
      probability of occurrence is increased by any increase in the electrical
      heterogeneity, in particular, the action potential duration heterogeneity of the
      ventricle. Focal ectopic activity would be readily detectable, but since re
      entrant arrhythmias are very rare events, even a large increase in their
      probability of occurrence still leaves them unlikely to be observed. Both of
      these two arrhythmogenic mechanisms would show a steep sigmoidal, or threshold
      dependence on induced current intensity, with the threshold for increasing the
      vulnerability to re-entry less than the threshold for initiating activity.
      Failure to observe them at fields less than 8 T provides only a lower bound for
      any threshold for arrhythmogenesis.

PMID- 15556668
TI  - The effects of static magnetic field on action potential propagation and
      excitation recovery in nerve.
AB  - Calculations using the Hodgkin-Huxley and one-dimensional cable equations have
      been performed to determine the expected sensitivity of conduction and
      refractoriness to changes in the time constant of sodium channel deactivation at
      negative potentials, as reported experimentally by Rosen (Bioelectromagnetics 24
      (2003) 517) when voltage-gated sodium channels are exposed to a 125 mT static
      magnetic field. The predicted changes in speed of conduction and refractory
      period are very small.

PMID- 15556669
TI  - International workshop "effects of static magnetic fields relevant to human
      health" Rapporteurs report: dosimetry and volunteer studies.

PMID- 15556670
TI  - A review of the current use of magnetic resonance imaging in pregnancy and safety
      implications for the fetus.
AB  - This paper presents an overview of the application of and risks of exposure to
      Magnetic Resonance Imaging (MRI) in pregnancy. It reviews the risks to the fetus
      by considering the hazards in terms of the three main components of an MRI
      system. These are the static magnetic field, the time-varying magnetic gradient
      fields and the pulsed radio frequency fields. The hazards discussed are
      biological effects, miscarriage, heating effects and acoustic noise exposure.
      This paper also presents a survey of MRI sites within the United Kingdom to
      ascertain the extent of MRI usage in pregnancy. To validate the situation of MRI
      in pregnancy a survey was sent to 352 MR units throughout the United Kingdom. The
      questions were grouped to assess (a) maternal MRI diagnosis (b) fetal MRI and (c)
      work practices for pregnant MRI staff. The results showed that 91% of sites were
      imaging pregnant women in need of diagnosis in the second and third trimester.
      This paper highlights that MRI can add information for fetal central nervous
      system abnormalities identified by ultrasound screening, however within the UK
      direct fetal imaging was only performed in 8% of sites. This paper indicates the
      need for research to be undertaken for specific MRI clinical conditions. It also
      advises that risk assessment for pregnant staff working in MRI is performed, and
      that there is a clear need for further research into the effects of MRI in
      pregnancy as there is a need for clear authoritive advice.

PMID- 15556671
TI  - WHO health risk assessment process for static fields.
AB  - The World Health Organization (WHO) has a commitment to helping Member States
      achieve safe, sustainable and health-enhancing human environments, protected from
      biological, chemical and physical agents. The latter includes advising on the
      health impact of electromagnetic fields (EMFs) and radiation. The results of the
      WHO/ICNIRP/NRPB workshop on static magnetic fields, published in this volume,
      provide a valuable and much needed contribution to the health risk assessment of
      exposure to static electric and magnetic fields, which is currently being
      coordinated by the WHO's International EMF Project. This WHO health risk
      assessment will be published as an environmental health criteria (EHC) monograph
      in early 2005. This paper briefly gives an overview of the process of developing
      the WHO static fields EHC monograph, the criteria applied to studies that could
      contribute to the EHC, along with the 'weight-of-evidence' approach to health
      risk assessment. In addition, there is an increasing awareness of the need to
      account for uncertainty in the science database. This is traditionally addressed
      by further research, and the EMF project addresses these needs through the
      development of a 'research agenda'. However, research programmes may take several
      years to complete, and the long latency associated with diseases such as cancer
      in people may also preclude a rapid outcome in some studies. The issue of current
      uncertainty is being addressed by the WHO EMF project through the development of
      a 'precautionary framework' in which precautionary measures will be applied to
      policy recommendations.

PMID- 15556672
TI  - Rapporteur report: implications for exposure guidelines.
AB  - There is a paucity of information regarding the long-term health effects
      associated with exposure to static magnetic fields. Perceptual and other acute
      effects have been demonstrated above a threshold of about 2 T, and these form the
      basis for human exposure standards at present. Exposures well above this
      threshold are increasingly becoming more common as the technology associated with
      magnetic resonance imaging advances. Therefore, priority should be given to
      assessing the health risks associated with exposures to such fields. Studies
      should include a prospective cohort study investigating cancer risks of workers
      and patients exposed to fields in excess of 2 T, a study investigating effects on
      human cognitive performance from repeated exposures, and a molecular biology
      study investigating acute changes in genomic responses in volunteers exposed to
      fields of up to 8 T. Studies investigating the effects of long-term exposure on
      cancer, and on neurobehavioural development are also recommended using animals,
      where the use of transgenic models is encouraged. In addition, dosimetric studies
      should be conducted using high-resolution male, female and pregnant voxel
      phantoms, as should theoretical studies investigating the local currents induced
      in the eye and in the heart by movement during exposure. Finally, studies are
      recommended to investigate further the ability of static magnetic fields to
      significantly affect radical pair reactions in biological systems.

PMID- 15556673
TI  - Kainate receptor trafficking: physiological roles and molecular mechanisms.
AB  - Recently, there has been intense interest in the mechanisms regulating the
      trafficking and synaptic targeting of kainate receptors in neurons. This topic is
      still in its infancy when compared with studies of trafficking of other
      ionotropic glutamate receptors; however, it is already clear that mechanisms
      exist for subunit- and splice variant-specific trafficking of kainate receptors.
      There is also enormous diversity of kainate receptor targeting, with the best
      studied neurons in this regard being hippocampal CA3 pyramidal neurons and CA1
      GABAergic interneurons. This review summarizes the current state of knowledge on
      this topic, focusing on the molecular mechanisms of kainate receptor trafficking
      and the potential for these mechanisms to regulate neuronal kainate receptor
      function.

PMID- 15556674
TI  - Mutant G-protein-coupled receptors as a cause of human diseases.
AB  - G-protein-coupled receptors (GPCR) are involved in directly and indirectly
      controlling an extraordinary variety of physiological functions. Their key roles
      in cellular communication have made them the target for more than 60% of all
      currently prescribed drugs. Mutations in GPCR can cause acquired and inherited
      diseases such as retinitis pigmentosa (RP), hypo- and hyperthyroidism,
      nephrogenic diabetes insipidus, several fertility disorders, and even carcinomas.
      To date, over 600 inactivating and almost 100 activating mutations in GPCR have
      been identified which are responsible for more than 30 different human diseases.
      The number of human disorders is expected to increase given the fact that over
      160 GPCR have been targeted in mice. Herein, we summarize the current knowledge
      relevant to understanding the molecular basis of GPCR function, with primary
      emphasis on the mechanisms underlying GPCR malfunction responsible for different
      human diseases.

PMID- 15556675
TI  - Protein kinases in vascular smooth muscle tone--role in the pulmonary vasculature
      and hypoxic pulmonary vasoconstriction.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is an adaptive mechanism that in the
      normal animal diverts blood away from poorly ventilated areas of the lung,
      thereby maintaining optimal ventilation-perfusion matching. In global hypoxia
      however, such as in respiratory disease or at altitude, it causes detrimental
      increases in pulmonary vascular resistance and pulmonary artery (PA) pressure.
      The precise intracellular pathways and mechanisms underlying HPV remain unclear,
      although it is now recognised that both an elevation in smooth muscle
      intracellular [Ca2+] and a concomitant increase in Ca2+ sensitivity are involved.
      Several key intracellular protein kinases have been proposed as components of the
      signal transduction pathways leading to development of HPV, specifically Rho
      kinase, non-receptor tyrosine kinases (NRTK), p38 mitogen activated protein (MAP)
      kinase, and protein kinase C (PKC). All of these have been implicated to a
      greater or lesser extent in pathways leading to Ca2+ sensitisation, and in some
      cases regulation of intracellular [Ca2+] as well. In this article, we review the
      role of these key protein kinases in the regulation of vascular smooth muscle
      (VSM) constriction, applying what is known in the systemic circulation to the
      pulmonary circulation and HPV. We conclude that the strongest evidence for direct
      involvement of protein kinases in the mechanisms of HPV concerns a central role
      for Rho kinase in Ca2+ sensitisation, and a potential role for Src-family kinases
      in both modulation of Ca2+ entry via capacitative Ca2+ entry (CCE) and activation
      of Rho kinase, though others are likely to have indirect or modulatory
      influences. In addition, we speculate that Src family kinases may provide a
      central interface between the proposed hypoxia-induced generation of reactive
      oxygen species by mitochondria and both the elevation in intracellular [Ca2+] and
      Rho kinase mediated Ca2+ sensitisation.

PMID- 15556676
TI  - Positive and negative allosteric modulation of metabotropic glutamate receptors:
      emerging therapeutic potential.
AB  - Metabotropic glutamate receptors (mGluRs) modulate neuronal activity in the
      central and peripheral nervous systems, and since their discovery have attracted
      considerable attention as putative therapeutic targets for a range of
      neurological and psychiatric disorders. A number of competitive agonists and
      antagonists acting at the N-terminal glutamate binding site have been identified,
      the majority of which are conformationally constrained or substituted amino acid
      analogues. These ligands have greatly facilitated investigation of the
      physiological and pathological roles of the receptor family. However, their
      utility and therapeutic potential has been restricted by relatively poor
      bioavailability and central nervous system (CNS) penetration, as well as limited
      chemical tractability and, generally, a lack of selectivity for individual
      mGluRs. Recently, a number of non-competitive mGluR ligands have been identified
      which bind within the receptor transmembrane heptahelical domain. These include
      both positive and negative allosteric modulators. Positive allosteric modulators
      do not exhibit intrinsic agonism but facilitate agonist-mediated receptor
      activity. Negative allosteric modulators include both non-competitive antagonists
      and inverse agonists. Allosteric modulation offers the potential for improved
      selectivity, particularly for individual receptors within the mGluR family, and
      enhanced chemical tractability relative to competitive agonists/antagonists. In
      addition, positive allosteric modulation provides a distinct, and perhaps
      superior, profile to receptor agonism, offering the potential for facilitation of
      physiologically appropriate receptor activation with reduced liability for
      receptor desensitisation and/or tolerance. Thus, the emerging field of positive
      and negative allosteric modulation of the mGluR family offers considerable
      promise for the development of novel therapeutics.

PMID- 15556677
TI  - Antithymocyte globulin is associated with complement deposition in cardiac
      transplant biopsies.
AB  - Polyclonal antithymocyte globulin preparations contain antibodies with reactivity
      to endothelial cells. Therefore, we investigated whether treatment with this
      reagent caused complement deposition in human cardiac transplants. Frozen tissue
      was available from endomyocardial biopsies of 75 patients, who were transplanted
      between April 1995 and April 2000. Nine of these patients were converted from
      cyclosporin A (CsA) to horse antithymocyte globulin (ATGAM) in the first month
      after transplantation. All of the biopsies were stained by immunofluorescence for
      C4d as evidence of activation of the classical pathway of complement. In
      addition, biopsies from patients treated with ATGAM and control patients were
      stained for deposition of horse immunoglobulin (Ig)G. All nine patients who
      received ATGAM had deposition of horse IgG and C4d. Two color stains demonstrated
      that the horse IgG colocalized with the C4d staining. No staining for horse IgG
      or C4d was evident in biopsies obtained before ATGAM treatment. Likewise, no
      staining for horse IgG was detected in seven control patients who had C4d
      staining. Most patients treated with ATGAM had no histologic evidence of
      rejection, but did have myocyte damage and macrophage infiltration. Thus
      prophylactic treatment with ATGAM is associated with the deposition of horse IgG
      and activation of complement in the transplant.

PMID- 15556678
TI  - ATG induction is associated with an increase in anti-HLA antibodies after kidney
      transplantation.
AB  - Anti-human histocompatibility antigen antibodies (HLA-Ab) are deleterious after
      kidney transplant and may be increased after T-cell depleting agents are given. A
      retrospective case control study was conducted to evaluate increase in HLA-Ab in
      27 kidney transplant recipients who had received antithymocyte globulin (ATG)
      induction compared with 27 control subjects. A greater than 10% increase in class
      I or class II HLA-Ab was found in 6 (22.2%) of ATG subjects versus only 1 (3.7%)
      of non-ATG subjects (p = 0.05). In females, 6/14 ATG subjects developed increased
      HLA-Ab > or =10% compared with none of the control subjects (p = 0.016). In
      sensitized subjects, 4/10 in the ATG group developed increased HLA-Ab > or =10%
      versus none of the controls (p = 0.043). There was no difference in number or
      severity of acute rejection episodes or estimated glomerular filtration rate 6
      months after transplant between the two treatment groups. We conclude that ATG
      induction may result in increased posttransplant HLA-Ab, particularly in subjects
      at higher immunologic risk. Further studies are necessary to determine the
      natural history, clinical consequences, appropriate therapy, and mechanisms
      responsible for HLA-Ab in this setting.

PMID- 15556679
TI  - Detection and specification of noncomplement binding anti-HLA alloantibodies.
AB  - The aim of the study was to investigate the distribution of human leukocyte
      antigen (HLA) -specific immunoglobulin (Ig) isotypes/subclasses in alloimmunized
      patients awaiting a kidney retransplant. Sera from 102 patients were analyzed for
      the presence of anti-HLA-A, anti-HLA-B alloantibodies by complement-dependent
      cytotoxicity test with the addition of dithiothreitol (CDC+DTT). Furthermore,
      anti-HLA class I and class II alloantibodies were determined using a commercial
      solid-phase (enzyme-linked immunosorbent assay [ELISA]) system. The respective
      isotypes/subclasses were defined by replacing the IgG1-4 secondary antibody with
      IgG1-, IgG2-, IgG3-, IgG4-, IgA1-, IgA2-, and IgM-specific antibodies. The HLA
      specificities of the noncomplement-binding IgG2 and IgG4 antibodies were
      determined and compared with the mismatches from the failed transplants. Thirty
      eight of 102 (37%) sera were positive in the class I CDC+DTT, in contrast to 41
      of 102 (40%) detected by class I ELISA and 47 of 102 (46%) by class II ELISA.
      Seventeen of 102 (17%) positive reaction were observed for the IgM-isotype,
      whereas none were detected for the IgA-isotype. Twenty-five of 102 (25 %) sera
      contained noncomplement-binding IgG2 and/or IgG4 antibodies; in the majority of
      the cases, 22 of 25 (88%) were directed against the organ donor antigen. These
      data show that donor-specific, noncomplement-binding IgG2 and IgG4 alloantibodies
      exist with high prevalence in HLA-immunized retransplant candidates. Therefore, a
      thorough antibody screening workup, including CDC with or without DTT and ELISA
      screening should be performed for patients before they reenter the waiting list.
      Defining the Ig isotypes and subclasses can be helpful to explain inconsistent
      results.

PMID- 15556680
TI  - Overlap between molecular markers expressed by naturally occurring CD4+CD25+
      regulatory T cells and antigen specific CD4+CD25+ and CD8+CD28- T suppressor
      cells.
AB  - Alloantigen specific CD8+CD28- T suppressor (TS) cells differ from naturally
      occurring CD4+CD25+ T-regulatory (natural TR) cells not only by their phenotype
      but also by their mechanism of action. Natural TR have been extensively studied,
      leading to the identification of characteristic "molecular markers" such as
      Forkhead box P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor
      related protein (GITR) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
      We have investigated the expression of these genes in alloantigen specific TS and
      CD4+CD25+ T regulatory (TR) cells and found that they are expressed at levels
      similar to those observed in natural TR. Furthermore, similar to natural
      CD4+CD25+ TR, antigen-specific CD8+CD28-CD62L+ TS cells have more suppressive
      capacity than CD8+CD28-CD62L- TS cells. In spite of these similarities, natural
      TR are not antigen-specific and inhibit other T cells by T cell-to-T cell
      interaction, whereas TS are antigen-specific and exert their inhibitory function
      by interacting with antigen-presenting cells and render them tolerogenic to other
      T cells. The molecular characterization of TS cells may contribute to a better
      understanding of mechanisms involved in inhibition of immune responses in
      autoimmunity, transplantation, and chronic viral infection.

PMID- 15556681
TI  - Optimization of an elispot assay to detect cytomegalovirus-specific CD8+ T
      lymphocytes.
AB  - Various arguments suggest that CD8+ T lymphocytes play a major role in the
      control of cytomegalovirus (CMV) infection. The detection of CMV-specific CD8+ T
      cells may therefore provide additional information about CMV virus detection to
      predict the risk of development of CMV disease, especially in immunodepressed
      transplant recipients. We compared and tested various experimental conditions to
      optimize an enzyme-linked immunospot assay (Elispot) assay for the detection of
      CMV-specific CD8+ T lymphocytes. The indirect Elispot assay with one six-day in
      vitro sensitization step was found to be the most sensitive method to detect CMV
      specific CD8+ T cells compared to direct Elispot with unfractionated peripheral
      blood mononuclear cells or purified CD8+ T cells. We showed that low doses of
      interleukin-2 during the in vitro culture enhanced the sensitivity of this test,
      and tetramer staining was performed to verify the high efficiency of this in
      vitro stimulation step. We directly loaded the specific CMV peptide during the
      Elispot assay and demonstrated that the use of T2 cells did not improve its
      sensitivity. Elispot for the detection of interferon-gamma appears to be more
      sensitive and reliable than measurement of tumor necrosis factor alpha or
      granzyme B. This technique was successfully applied to detect CMV-specific CD8+ T
      cells in human leukocyte antigen A2 (HLA-A2) and HLA-B7 healthy patients and in
      one lymphopenic post-transplant patient with positive CMV serology. This highly
      sensitive test may be a useful tool to assess T-cell immunity directed against
      CMV in immunodepressed patients.

PMID- 15556682
TI  - CD25+ regulatory cells from HLA-DQ8 transgenic mice are capable of modulating
      collagen-induced arthritis.
AB  - In the last decade, CD4+CD25+ T regulatory cells have been implicated in the
      protection against autoimmune diseases. The human DQ8 major histocompatibility
      complex (MHC) class II molecule is associated with rheumatoid arthritis (RA) and
      various other autoimmune diseases in humans. The human leukocyte antigen (HLA)
      DQ8 transgenic mouse, containing the human DQ8 MHC class II molecule, is
      predisposed toward collagen-induced arthritis. However, the biologic pathways
      responsible for DQ8-associated autoimmunity have yet to be defined, including
      possible defects in the CD4+CD25+ T regulatory cell compartment. To explore this
      concept, we examined the suppressive capacity of CD4+CD25+ T regulatory cells
      from DQ8 transgenic mice in vitro and, using CD25-specific depleting antibodies,
      investigated their influence on collagen-induced arthritis in vivo. CD4+CD25+ T
      regulatory cells isolated from DQ8 transgenic mice were found to be sufficient
      suppressors of splenocyte proliferation and interferon (INF)-gamma production.
      Furthermore, depletion of these cells before immunization led to significant
      increases in arthritis severity, collagen-specific antibodies, and INF-gamma
      production. These results indicate that HLA-DQ8 mice contain naturally occurring
      CD25+ regulatory cells that modulate collagen-induced arthritis and imply that
      DQ8 expression does not hinder the development of CD25+ T regulatory cells.

PMID- 15556683
TI  - Endogenous IL-4 and IFN-gamma are essential for expression of Th2, but not Th1
      cytokine message during the early differentiation of human CD4+ T helper cells.
AB  - CD4+ T cells can be divided into several distinct effector subpopulations,
      including Th1 and Th2. Human Th1 cells are essential for the establishment of
      cellular immune responses, whereas Th2 cells for immunoglobulin E synthesize by B
      cells and immunoregulation. This study determines the involvement of exogenously
      and endogenously produced T cell-derived cytokines during early differentiation
      of naive CD4+ T cells into Th1 and Th2 cells. Cytokine gene expression of
      purified experienced and naive CD4+T cells in the presence or absence of Th
      directing cytokines and neutralizing anti-cytokine antibodies, was determined at
      early (20 and 40 h) time points, after in vitro activation. These studies
      demonstrated that: (1) endogenously produced, T cell-derived cytokines
      (interferon [IFN]-gamma and interleukin [IL]-4), play an important role in the
      regulation of early gene expression of Th2, but not Th1 type cytokines; (2) Th1
      related cytokines, IFN-gamma, and IL-2, are preferentially expressed in cultures
      directed toward Th1, as compared with Th2; and (3) IL-4 and IFN-gamma showed
      early message expression in both differentiating populations, indicating a mixed
      profile of Th1 and Th2 cytokine production in early human Th cell development.
      These findings point to the critical role for endogenously produced cytokines in
      the early differentiation of human Th1 or Th2 cells.

PMID- 15556684
TI  - Correlation of human decidual and cord blood mononuclear cell cytokine
      production.
AB  - Human decidua has been shown to produce a number of cytokines. We hypothesized
      that decidual cytokine production influences cord blood mononuclear cell (CBMC)
      cytokine production and that cytokine profiles of decidua from allergic women
      differ from those of decidua from nonallergic women. Using enzyme-linked
      immunosorbent assay, we measured unstimulated and concanavalin A/phorbol
      myristate acetate-stimulated production of interleukin-4 (IL-4), IL-5, IL-10, IL
      13 and interferon- gamma (IFN-gamma) by decidual explants from 59 healthy women
      delivered by unlabored cesarean section and from corresponding CBMCs in 39 of the
      59. Except for IL-10, there was little or no unstimulated cytokine production.
      There was a strong correlation between stimulated decidual and stimulated CBMC
      IFN-gamma production (p = 0.01). In allergic women the ratio of IL-13 to IL-4
      production was increased in stimulated explants (p = 0.03). Stimulated CBMCs from
      infants of allergic mothers were more likely to produce detectable levels of IL-5
      than those from infants of nonallergic mothers (p = 0.04) and had a tendency
      toward higher IL-13 levels as well (p = 0.07). These results suggest that
      maternal and fetal IFN-gamma production is closely linked and that maternal
      allergy appears to influence cytokine production in the neonate for IL-5 and
      possibly IL-13.

PMID- 15556685
TI  - Recombinant adenovirus-transduced human dendritic cells engineered to secrete
      interleukin-10 (IL-10) suppress Th1-type responses while selectively activating
      IL-10-producing CD4+ T cells.
AB  - Recombinant adenoviruses (rAd) are efficient tools for genetic modification of
      human dendritic cells (DC) in vitro. Infection of DCs by rAd encoding beta
      galactosidase (betagal) results in partial maturation of DCs, as witnessed by the
      upregulation of major histocompatibility complex and costimulatory molecules.
      Accordingly, these DCs are more potent stimulators of Th1-type proliferative
      responses. We now demonstrate that infection of immature DCs with rAd encoding
      human interleukin (IL)-10 results in the secretion by the DCs of large amounts of
      IL-10, while not affecting expression of activation markers indicative of partial
      DC maturation. In contrast to rAd-betagal-infected DCs, rAdIL-10-infected DCs are
      very poor stimulators of monoclonal and polyclonal Th1-type responses. Instead,
      stimulation of nonpolarized CD4+ T-cell cultures with rAdIL-10-infected DCs
      selectively activates and expands an IL-10-producing CD4+ T-cell subset capable
      of suppressing Th1 responses in vitro. Our data argue that rAd-infected human DCs
      genetically engineered to produce IL-10 may be exploited for the modulation of
      harmful Th1-type responses in transplantation and autoimmune diseases.

PMID- 15556686
TI  - Selective developmental defects of cord blood antigen-presenting cell subsets.
AB  - Defective antigen-presenting cell (APC) function has been hypothesized to
      contribute to increased infection susceptibility in newborns. We used
      multiparameter flow cytometry to characterize APC subsets in adult peripheral
      blood (APB) and cord blood (CB). APB had a higher proportion of CD11c+ dendritic
      cells (DC), whereas CB mainly contained CD123+ DC. APB was enriched in
      CD16+CD11c+ DC subset, whereas CD34+CD11c-CD123lo cells were prominent in CB.
      Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production was
      dampened in myeloid DC and monocytes from CB, whereas IL-1alpha production was
      not different. The reduction in TNF-alpha response did not appear to result from
      reduced surface detection of LPS, because CD14, toll-like receptor (TLR)-4 and
      TLR-2 levels were not reduced in CB APC compared with APB cells. Also, there was
      no correlation between TLR-2 or TLR-4 levels and TNF-alpha production in myeloid
      DC and monocytes. CB monocytes had lower surface HLA-DR immediately ex vivo. Both
      APB and CB monocytes upregulated HLA-DR after incubation, but an additional LPS
      induced increase in HLA-DR was suggested only in APB monocytes. APB monocytes
      also showed a greater LPS-induced increase in CD40 expression. Together, our data
      show significant, selective differences in circulating APC between neonates and
      adults.

PMID- 15556687
TI  - Upregulation and atypical expression of the CD1 molecules on monocytes in sickle
      cell disease.
AB  - Human CD1 group I molecules CD1a, b, and c are expressed on antigen-presenting
      cells, notably dendritic cells, and implicated in glycolipids presentation to T
      lymphocytes. Expression of CD1 on monocytes is a hallmark of their activation.
      Because monocyte activation has been reported during steady state disease in
      sickle cell anemia (SCA) patients, we have analyzed CD1 expression on monocytes
      from 45 SCA patients originating from Africa and 27 healthy control subjects. CD1
      expression was detected on monocytes in the majority of SCA patients (75%),
      whereas it was not observed in the vast majority of the control group (70.4%).
      CD1b and CD1c were highly expressed in Sbeta thalassemia patients and CD1a
      expression was predominant in SDPunjab patients. This expression of the CD1
      molecules is correlated with an increased expression of the major
      histocompatibility complex class II invariant chain (CD74). Finally, we have
      observed that the majority of SCA patients (68%) express only two or one CD1
      isoforms. This study demonstrates the particular phenotype of SCA monocytes
      intermediate between normal resting and activated monocytes, a phenotype that
      could have consequences on regulation of the infection outcome.

PMID- 15556688
TI  - The characteristics of human NKT cells in lung cancer--CD1d independent
      cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell
      response in lung cancer patients.
AB  - The activation of human Valpha24+Vbeta11+natural killer T cells (NKT) cells
      (Valpha24 NKT cells) induces effective antitumor responses with secondary immune
      effects through activation of conventional T cells and natural killer cells. In
      this study, we attempted to analyze the characteristics of human NKT cells in
      lung cancer patients. Valpha24 NKT cells stimulated with alpha-GalCer from
      healthy volunteers exhibited direct cytotoxic activity against two (RERF-LC-OK
      and PC-3) of seven human lung cancer cell lines studied. Cytotoxicity by Valpha24
      NKT cells against human lung cancer cells was dependent on the perforin pathway
      and independent of Fas/FasL pathway. Intracellular adhesion molecule (ICAM)-1
      expression on tumor cells was clearly associated with the cytotoxicity of
      Valpha24 NKT cells. On the other hand, the proportion of Valpha24 NKT cells in
      the patients with lung cancer was lower than that in the healthy volunteers.
      Furthermore, the proliferative response of Valpha24 NKT cells to alpha-GalCer was
      significantly lower in the peripheral blood mononuclear cells in the patients
      with lung cancer. Addition of granulocyte colony-stimulating factor moderately
      restored the low proliferative response of Valpha24 NKT cells in the patients
      with lung cancer, however the percentage by which the response was restored in
      these patients was still lower than the natural response in healthy volunteers.
      These results suggest that Valpha24 NKT cells may play a pivotal role or the
      antitumor response in lung cancer.

PMID- 15556689
TI  - The short cytoplasmic tail of HLA-G determines its resistance to HIV-1 Nef
      mediated cell surface downregulation.
AB  - During infection with the human immunodeficiency virus type 1 (HIV-1), selective
      downregulation of major histocompatibility complex (MHC) class I molecules by Nef
      protein allows infected cells to be protected from natural killer (NK) cell lysis
      and to escape the HIV-specific cytotoxic T-lymphocyte response. The nonclassical
      MHC class I molecule human leukocyte antigen (HLA)-G is mainly expressed in
      placental tissues and in thymic epithelial cells. Using chimeric molecules and
      flow cytometry, we show that in contrast with HLA-A2, the non classical MHC class
      I molecule HLA-G is resistant to Nef-induced cell surface downregulation solely
      because of the length of its intracytoplasmic domain. Moreover, confocal
      microscopy analysis indicates that Nef does not delocalize HLA-G molecules from
      the cell surface, whereas HLA-G molecules extended with the cytoplasmic tail of
      HLA-A2 accumulate intracellularly with Nef. Together, these data demonstrate that
      the short cytoplasmic tail of HLA-G confers resistance to Nef-induced
      downregulation and intracellular accumulation. This resistance may have
      functional consequences during the course of HIV infection.

PMID- 15556690
TI  - Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients
      show a different profile of major histocompatibility complex class II alleles.
AB  - Comparison of human leukocyte antigen (HLA) frequencies in patients with
      hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients
      with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed
      previously. To this aim, we investigated the distribution of HLA class II alleles
      in two selected groups of HCV-infected patients. Group 1 included 50 patients
      with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A
      control group included 144 hospitalized patients without NHL or HCC and who were
      negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies.
      Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were
      used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous
      clearance of HCV infection, was lower in HCC subjects than in controls, whereas
      HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest
      different pathogenic pathways in HCC and in NHL development. In patients with HCV
      associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11,
      was found, probably because of a better HLA class II-associated virus clearance.
      By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated
      NHL. These data suggest that NHL and HCC development may be associated to a
      different response with respect to chronic HLA class II-restricted antigen
      presentation (perhaps a switch toward CD4+Th2 response in NHL?) or,
      alternatively, that these alleles could be in linkage disequilibrium to unrelated
      gene(s), or are in synergy with other immunomodulatory genes that may confer
      increased risk for NHL.

PMID- 15556691
TI  - Interferon-gamma polymorphisms correlate with duration of survival in pancreatic
      cancer.
AB  - Despite progress in diagnosis and staging, pancreatic cancer still has a poor
      prognosis and it remains difficult to predict duration of survival in advanced
      pancreatic cancer. Nutritional decline, or cachexia, is a contributory factor to
      decreased survival in advanced pancreatic carcinoma, and it has been demonstrated
      that proinflammatory cytokines give rise to cachexia. Interferon (IFN)-gamma is a
      proinflammatory cytokine whose administration increases survival outcomes in a
      variety of cancers. The human IFN-gamma gene has a variable length CA-repeat
      sequence, the length that has been shown to influence IFN-gamma production. The
      current study was performed to ascertain whether polymorphisms of the IFN-gamma
      gene would influence survival of individuals with advanced pancreatic cancer. The
      study demonstrated that the presence of allele 2 (12 CA repeats) was consistently
      associated with increased duration of survival after confirmation of
      nonresectable pancreatic carcinoma. We therefore propose that the presence of
      allele 2 may be a useful marker for patient outcome.

PMID- 15556692
TI  - Nomenclature for factors of the HLA system, update June 2004.

PMID- 15556693
TI  - Nomenclature for factors of the HLA system, update July 2004.

PMID- 15556694
TI  - The effects of atomic force microscopy upon nominated living cells.
AB  - This work describes a system for precise re-location of cells within a monolayer
      after atomic force imaging. As we know little about probe interaction with soft
      biological surfaces any corroborative evidence is of great importance. For
      example, it is of paramount importance in living cell force microscopy that
      interrogated cells can be re-located and imaged by other corroborative
      technologies. Methodologies expressed here have shown that non-invasive force
      parameters can be established for specific cell types. Additionally, we show that
      the same sample can be transferred reliably to an SEM. Results here indicate that
      further work with live cells should initially establish appropriate prevailing
      force parameters and that cell damage should be checked for before and after an
      imaging experiment.

PMID- 15556695
TI  - Modeling electric-field-sensitive scanning probe measurements for a tip of
      arbitrary shape.
AB  - We present a numerical method to model electric-field-sensitive scanning probe
      microscopy measurements which allows for a tip of arbitrary shape and invokes
      image charges to exactly account for a sample dielectric overlayer. The method is
      applied to calculate the spatial resolution of a subsurface charge accumulation
      imaging system, achieving reasonable agreement with experiment.

PMID- 15556696
TI  - Symmetries in BF and HAADF STEM image calculations.
AB  - Reductions in bright-field (BF) scanning transmission electron microscopy (STEM)
      and high-angle annular dark-field (HAADF) STEM image calculations with the aid of
      Bloch wave symmetry are discussed under assumptions that an absorption potential
      is written by a local potential and a zero-order Laue zone lies parallel to the
      crystal surface. Translational symmetry allows us to take only partial incident
      beams in the first Brillouin zone instead of enormous number of partial incident
      beams in a large convergent disk. Two dimensional point group confines partial
      incident beams to an irreducible area in addition to factoring a dispersion
      matrix into noninteracting submatrices on a high symmetry line using the
      projection operator. The drastic reductions in computing time and memory enable
      us to readily calculate various BF STEM and HAADF STEM images. The validity and
      accuracy are demonstrated in comparisons with high resolution experimental BF
      STEM and HAADF STEM images.

PMID- 15556697
TI  - Location specific in situ TEM straining specimens made using FIB.
AB  - A method has been devised and demonstrated for producing in situ straining
      specimens for the transmission electron microscope (TEM) from specific locations
      in a sample using a dual-beam focused ion beam (FIB) instrument. The specimen is
      removed from a polished surface in the FIB using normal methods and then attached
      to a pre-fabricated substrate in the form of a modified TEM tensile specimen. In
      this manner, specific features of the microstructure of a polished optical mount
      can be selected for in situ tensile straining. With the use of electron
      backscattered diffraction (EBSD), this technique could be extended to select
      specific orientations of the specimen as well.

PMID- 15556698
TI  - Automated spatial drift correction for EFTEM image series.
AB  - Energy filtering transmission electron microscopy (EFTEM) is a widely used
      technique in many areas of scientific research. Image contrast in energy-filtered
      images arises from specific scattering events such as the ionization of atoms. By
      combining a set of two or more images, relative sample thickness maps or
      elemental distribution maps can be easily created. It is also possible to acquire
      a whole series of energy-filtered images to do more complex data analysis.
      However, whenever several images are combined to extract certain information,
      problems are introduced due to sample drift between the exposures. In order to
      obtain artifact-free information, this spatial drift has to be taken care of.
      Manual alignment by overlaying and shifting the images to find the best overlap
      is usually very accurate but extremely time consuming for larger data sets. When
      large amounts of images are recorded in an EFTEM series, manual correction is no
      longer a reasonable option. Hence, automatic routines have been developed that
      are mostly based on the cross-correlation algorithm. Existing routines, however,
      sometimes fail and again make time consuming manual adjustments necessary. In
      this paper we describe a new approach to the drift correction problem by
      incorporating a statistical treatment of the data and we present our
      statistically determined spatial drift (SDSD) correction program. We show its
      improved performance by applying it to a typical EFTEM series data block.

PMID- 15556699
TI  - On the transport of intensity technique for phase retrieval.
AB  - The Transport of Intensity technique is becoming a viable alternative to electron
      holography for phase retrieval in Transmission Electron Microscopy. However,
      several issues are still to be clarified in order to ascertain the applicability
      of the technique; among them, the controversy regarding its geometrical or wave
      optical nature, as related to the phase detection limit. We show here that the
      Transport of Intensity is a wave-optical technique that works in a special regime
      of small defocus where the image intensity is linear with the defocus parameter.
      By a simple analytical example we show that the Transport of Intensity correctly
      reconstructs the electron optical phase shift even when the phase is smaller than
      pi, a value defining the boundary between the geometrical and wave approaches.
      Another example is given, the reconstruction of a phase jump, accompanied with
      experimental support showing that phase retrieval by Electron Holography and
      Transport of Intensity techniques yields results in good agreement.

PMID- 15556700
TI  - Influence of the atomic force microscope tip on the multifractal analysis of
      rough surfaces.
AB  - In this paper, the influence of atomic force microscope tip on the multifractal
      analysis of rough surfaces is discussed. This analysis is based on two methods,
      i.e. on the correlation function method and the wavelet transform modulus maxima
      method. The principles of both methods are briefly described. Both methods are
      applied to simulated rough surfaces (simulation is performed by the spectral
      synthesis method). It is shown that the finite dimensions of the microscope tip
      misrepresent the values of the quantities expressing the multifractal analysis of
      rough surfaces within both the methods. Thus, it was concretely shown that the
      influence of the finite dimensions of the microscope tip changed mono-fractal
      properties of simulated rough surface to multifractal ones. Further, it is shown
      that a surface reconstruction method developed for removing the negative
      influence of the microscope tip does not improve the results obtained in a
      substantial way. The theoretical procedures concerning both the methods, i.e. the
      correlation function method and the wavelet transform modulus maxima method, are
      illustrated for the multifractal analysis of randomly rough gallium arsenide
      surfaces prepared by means of the thermal oxidation of smooth gallium arsenide
      surfaces and subsequent dissolution of the oxide films.

PMID- 15556701
TI  - The magic angle: a solved mystery.
AB  - We resolve the long-standing mysterious discrepancy between the experimental
      magic angle in EELS--approximately 2theta(E)--and the quantum mechanical
      prediction of approximately 4theta(E). A relativistic approach surpassing the
      usually applied kinematic correction yields a magic angle close to the
      experimental value. The reason is that the relativistic correction of the
      inelastic scattering cross section in anisotropic systems is significantly higher
      than in isotropic ones.

PMID- 15556702
TI  - Noise bias in the refinement of structures derived from single particles.
AB  - One of the main goals in the determination of three-dimensional macromolecular
      structures from electron microscope images of individual molecules and complexes
      (single particles) is a sufficiently high spatial resolution, about 4 A, at which
      the interpretation with an atomic model becomes possible. To reach high
      resolution, an iterative refinement procedure using an expectation maximization
      algorithm is often used that leads to a more accurate alignment of the positional
      and orientational parameters for each particle. We show here the results of
      refinement algorithms that use a phase residual, a linear correlation
      coefficient, or a weighted correlation coefficient to align individual particles.
      The algorithms were applied to computer-generated data sets that contained
      projections from model structures, as well as noise. The algorithms show
      different degrees of over-fitting, especially at high resolution where the signal
      is weak. We demonstrate that the degree of over-fitting is reduced with a
      weighting scheme that depends on the signal-to-noise ratio in the data. The
      weighting also improves the accuracy of resolution measurement by the commonly
      used Fourier shell correlation. The performance of the refinement algorithms is
      compared to that using a maximum likelihood approach. The weighted correlation
      coefficient was implemented in the computer program FREALIGN.

PMID- 15556703
TI  - HIV and the CCR5-Delta32 resistance allele.
AB  - The combination of molecular biology, epidemiology, virology, evolutionary and
      population genetics has enabled us to understand the delicate interplay between
      HIV and the CCR5-Delta32 HIV resistance allele. We here review and collect from
      the different approaches to show how they can be combined to elucidate the
      interaction between host and pathogen genetics in this system. We will present an
      overview of the normal role of CCR5, its involvement in HIV, the molecular
      biology of the CCR5-Delta32 allele and its probable origins. By focusing on this
      well-documented and important system we hope to demonstrate the power that such a
      "holistic" approach might offer in the study of infectious diseases.

PMID- 15556704
TI  - Pseudomonas fluorescens infection by bacteriophage PhiS1: the influence of
      temperature, host growth phase and media.
AB  - The influence of host growth temperature, phase and media, together with the
      effect of infection temperature on bacteriophage PhiS1 infection of Pseudomonas
      fluorescens were examined. The rates of cell lysis and phage release were
      determined and showed that the efficacy of phage infection was optimal with host
      cells grown and infected at 26 degrees C. The host physiological state also
      affected these rates. Infection was dependent on the presence of cell wall
      proteins with molecular weights of 17.5+/-1 and 99+/-5 kDa.

PMID- 15556705
TI  - Regulation of acetate and acetyl-CoA converting enzymes during growth on acetate
      and/or glucose in the halophilic archaeon Haloarcula marismortui.
AB  - Haloarcula marismortui formed acetate during aerobic growth on glucose and
      utilized acetate as growth substrate. On glucose/acetate mixtures diauxic growth
      was observed with glucose as the preferred substrate. Regulation of enzyme
      activities, related to glucose and acetate metabolism was analyzed. It was found
      that both glucose dehydrogenase (GDH) and ADP-forming acetyl-CoA synthetase (ACD)
      were upregulated during periods of glucose consumption and acetate formation,
      whereas both AMP-forming acetyl-CoA synthetase (ACS) and malate synthase (MS)
      were downregulated. Conversely, upregulation of ACS and MS and downregulation of
      ACD and GDH were observed during periods of acetate consumption. MS was also
      upregulated during growth on peptides in the absence of acetate. From the data we
      conclude that a glucose-inducible ACD catalyzes acetate formation whereas acetate
      activation is catalyzed by an acetate-inducible ACS; both ACS and MS are
      apparently induced by acetate and repressed by glucose.

PMID- 15556706
TI  - Identification, distribution pattern of IS231 elements in Bacillus thuringiensis
      and their phylogenetic analysis.
AB  - In order to better understand the fundamental biology of Bacillus thuringiensis,
      a single oligonucleotide primer (5'-CATSSCCATCAASYTAAVR-3') was used to
      investigate the distribution pattern of IS231 elements in B. thuringiensis by
      PCR. The results indicated that IS231 elements appeared in 20 standard strains
      and 107 of 111 China isolates. Three novel IS231, IS231J, IS231O and IS231Q, five
      variants and a mobile insertion cassette MICBth4 were cloned from eight standard
      strains of B. thuringiensis, respectively. Interestingly, BLAST analysis revealed
      that the 5' end of novel IS231J shared 99% identity in 495-bp with a DNA segment
      adjacent to the 3' end of B. thuringiensis vip1Ac gene (GenBank Accession No. ).
      Two phylogenetic trees of IS231 elements were constructed and analyzed by
      neighbor-joining and UPGMA methods from PHYLIP 3.6b program, respectively.

PMID- 15556707
TI  - Nitrogen regulation in Sinorhizobium meliloti probed with whole genome arrays.
AB  - Using whole genome arrays, we systematically investigated nitrogen regulation in
      the plant symbiotic bacterium Sinorhizobium meliloti. The use of glutamate
      instead of ammonium as a nitrogen source induced nitrogen catabolic genes
      independently of the carbon source, including two glutamine synthetase genes,
      various aminoacid transporters and the glnKamtB operon. These responses depended
      on both the ntrC and glnB nitrogen regulators. Glutamate repressible genes
      included glutamate synthase and a H+-translocating pyrophosphate synthase. The
      smc01041-ntrBC operon was negatively autoregulated in a glnB-dependent fashion,
      indicating an involvement of phosphorylated NtrC. In addition to the nitrogen
      response, glutamate remodelled expression of carbon metabolism by inhibiting
      expression of the Entner-Doudoroff and pentose phosphate pathways, and by
      stimulating gluconeogenetic genes independently of ntrC.

PMID- 15556708
TI  - Purification, characterization and functional analysis of an endo-arabinanase
      (AbnA) from Bacillus subtilis.
AB  - Bacillus subtilis synthesizes at least one arabinanase encoded by the abnA gene
      that is able to degrade the polysaccharide arabinan. Here, we report the
      expression in Escherichia coli of the full-length abnA coding region with a His6
      tag fused to the C-terminus. The recombinant protein was secreted to the
      periplasmic space and correctly processed by the E. coli signal peptidase. The
      substrate specificity of purified AbnA, the physico-chemical properties and
      kinetic parameters were determined. Functional analysis studies revealed Glu 215
      as a key residue for AbnA hydrolytic activity and indicated that in addition to
      AbnA B. subtilis secretes other enzyme(s) able to degrade linear 1,5-alpha-l
      arabinan.

PMID- 15556709
TI  - Cell envelope analysis of insensitive, susceptible or resistant strains of
      Leuconostoc and Weissella genus to Leuconostoc mesenteroides FR 52 bacteriocins.
AB  - Mesenterocins 52A and 52B belong to class II of lactic acid bacteria
      bacteriocins. To study susceptibility, insensitivity and resistance to these
      mesenterocins, four wild-type bacterial strains and four resistant strains, all
      from Leuconostoc or Weissella genus, were compared. Several cell envelope
      features were investigated: susceptibilities to antibiotics and to lysozyme, cell
      morphology and membrane phospholipids contents. The strain insensitive to the two
      mesenterocins appeared to be resistant to lysozyme and exhibited the highest
      resistance to antibiotics. Resistant strains displayed cell morphology
      modifications, several increases in antibiotic resistance and modifications in
      lysozyme susceptibility. Moreover, mesenterocin 52A-resistant strains displayed
      modifications in their membrane phospholipids, leading to a more cationic
      membrane. Insensitivity and resistance of Leuconostoc or Weissella strains seem
      to be due to various minor modifications of the membrane and/or of the cell wall.

PMID- 15556710
TI  - Role of Helicobacter pylori rfaJ genes (HP0159 and HP1416) in lipopolysaccharide
      synthesis.
AB  - The genome of Helicobacter pylori 26695 has been sequenced and the
      lipopolysaccharide (LPS) O sidechain of this strain has been shown to express
      both Lewis x and Lewis y units. To determine the role of HP0159 and HP1416, genes
      recognized as rfaJ homologs and implicated in LPS synthesis, isogenic mutants of
      H. pylori 26695 were generated. The LPS of mutant 26695::HP0159Kan did not
      express either Lewis epitope as detected by immunoblotting, whereas the control
      strain and 26695::HP1416Kan produced both epitopes. Structural analysis of the
      LPS of the mutants showed that HP0159 encodes an alpha(1,2/3)-glucosyltransferase
      whereas HP1416 encodes an alpha(1,2/4)-glucosyltransferase.

PMID- 15556711
TI  - Endophytic naphthopyrone metabolites are co-inhibitors of xanthine oxidase,
      SW1116 cell and some microbial growths.
AB  - Fractionation of the extract of Aspergillus niger. IFB-E003, an endophyte in
      Cyndon dactylon, gave four known compounds naphtho-gamma-pyrones rubrofusarin B,
      fonsecinone A, asperpyrone B and aurasperone A, which were further investigated
      biologically. Rubrofusarin B was shown to be cytotoxic to the colon cancer cell
      line SW1116 (IC50: 4.5 microgml-1), and aurasperone A inhibitory on XO (xanthine
      oxidase) (IC50: 10.9 micromoll-1). Moreover, the four naphtho-gamma-pyrones
      exhibited growth inhibitions against the five test microbes with MICs ranging in
      between 1.9 and 31.2 microgml(-1). The present recognition of rubrofusarin B and
      aurasperone A as strong co-inhibitors on XO, colon cancer cell and some microbial
      pathogens is of significance for the imperative discovery of new relevant
      therapeutic agents.

PMID- 15556712
TI  - Transformation of Lactobacillus plantarum by electroporation with in vitro
      modified plasmid DNA.
AB  - An improved method for the electrotransformation of Lactobacillus plantarum CECT
      220 (ATCC 8014) with plasmid DNA isolated from Escherichia coli is described. The
      two main modifications with respect to existing methods are: (i) isolation of
      plasmid DNA from E. coli JM110 grown in minimal medium and (ii) in vitro
      modification of the DNA by cell-free extracts of the host L. plantarum. Optimal
      electrotransformation was obtained with exponentially growing cells of L.
      plantarum concentrated to 6x10(9) cfu ml-1, with electric pulses of 13 kV cm-1 in
      cuvettes with 1 mm inter-electrode distance. We consider that this method
      constitutes a useful tool for routine manipulation of L. plantarum, and can
      probably be extended to other lactic acid bacteria.

PMID- 15556713
TI  - Differential gene expression during interactions between Heterobasidion annosum
      and Physisporinus sanguinolentus.
AB  - Using mRNA differential display we have identified differentially expressed genes
      in non-self-interacting vs. single mycelia of the conifer pathogen Heterobasidion
      annosum and the wood decomposing basidiomycete Physisporinus sanguinolentus.
      Altogether 39 differentially displayed bands were cloned and sequenced,
      corresponding to 21 unique genes, which were confirmed by semi-quantitative RT
      PCR to be differentially expressed. Further confirmation of differential gene
      expression was made by real time RT-PCR. All 10 genes identified from P.
      sanguinolentus had lower expression, while in H. annosum three genes had higher
      and eight lower expression in non-self-interacting mycelia vs. single mycelia.
      One of the induced genes showed high similarity to the Coprinus cinereus
      recA/RAD51 homolog (rah1) which is essential for homologous recombination, DNA
      repair and stress responses.

PMID- 15556714
TI  - A fibrinogen-binding protein of Staphylococcus lugdunensis.
AB  - A gene called fbl, encoding a Staphylococcus lugdunensis fibrinogen-binding
      protein, was identified by phage display. The encoded protein, Fbl, is a member
      of the Sdr-family, a group of staphylococcal cell surface proteins containing a
      characteristic serine-aspartate repeat region. The fibrinogen-binding domain was
      mapped to 313 amino acids, and shows 62% identity to the corresponding region in
      clumping factor (ClfA) from Staphylococcus aureus. Anti-serum against ClfA cross
      reacted with Fbl, and blocked S. lugdunensis adherence to fibrinogen. Twelve
      clinical isolates of S. lugdunensis analysed by Southern blot all had an fbl-like
      gene.

PMID- 15556715
TI  - Porphyromonas gingivalis induces its uptake by human macrophages and promotes
      foam cell formation in vitro.
AB  - Porphyromonas gingivalis is an etiologic agent of periodontal disease in humans,
      which has been linked to an increased risk for atherosclerosis-related events. In
      this study, we examined the effect of P. gingivalis infection on human
      macrophages with respect to foam cell formation, the hallmark of early
      atherogenesis, and the potential of P. gingivalis to induce its uptake by these
      cells. Human monocyte-derived macrophages were incubated with low density
      lipoprotein and infected with P. gingivalis FDC381 or its fimbriae deficient
      mutant, DPG3. Consistent with a role for fimbriae in this process, strain 381
      significantly increased foam cell formation as compared to DPG3. Recovery of
      viable P. gingivalis in antibiotic protection experiments was significantly
      higher for strain 381 than for DPG3. By transmission electron microscopy, the
      wild-type strain was shown to adhere to and enter THP-1 cells. These results
      suggest that properties of P. gingivalis which render it capable of adhering
      to/invading other cell types may also be operative in macrophages and play an
      important role in its atherogenic potential.

PMID- 15556716
TI  - Rapid detection of Mycoplasma dispar and M. bovirhinis using allele specific
      polymerase chain reaction protocols.
AB  - We describe an allele specific PCR based approach for the rapid detection of two
      bovine Mycoplasma species associated with respiratory disease. Specific and
      universal oligonucleotides were used in combination to detect the presence of
      single nucleotide polymorphisms within the 16S ribosomal DNA sequence. Presence
      of Mycoplasma 16S rDNA is indicated by the production of a single control
      fragment, whilst positive samples generate an alternative smaller specific
      product over the same region. This technique provides a reliable and sensitive
      method which, although widely used in human genetic screening, has not been
      documented for diagnosis of bacterial infection.

PMID- 15556717
TI  - The Aeromonas hydrophila LuxR homologue AhyR regulates the N-acyl homoserine
      lactone synthase, AhyI positively and negatively in a growth phase-dependent
      manner.
AB  - Aeromonas hydrophila is a pathogen of fish, amphibians and humans which produces
      N-acylhomoserine lactone quorum sensing signal molecules and possesses homologues
      of the Vibrio fischeri luxI and luxR quorum sensing genes termed ahyI and ahyR,
      respectively. The ahyI and ahyR genes of A. hydrophila comprise a divergon with a
      62 bp intergenic region and control biofilm maturation and extracellular protease
      production. Stationary phase culture supernatants from an ahyR but not an ahyI
      mutant contain N-butanoylhomoserine lactone (C4-HSL) which is shown to be
      required for maximal ahyI expression. To determine whether AhyR regulates ahyI,
      the expression of AhyI was followed throughout growth by Western blot analysis.
      This revealed that AhyI can be detected in the exponential phase but appears to
      be degraded in stationary phase in the parent A. hydrophila strain. In an ahyR
      mutant however, the AhyI protein is only produced in stationary phase but
      production is sustained suggesting that AhyR controls the timing of AhyI
      production and turnover. By using RT-PCR, we mapped the transcriptional start
      site of ahyI which revealed that the 12 bp symmetrical lux-box like sequence
      present in the 62 bp ahyRI intergenic region overlaps with the -10 region of the
      ahyI promoter. To determine whether AhyR could bind to the ahyRI intergenic
      region, the ahyR gene was expressed and purified as a maltose binding protein
      (MalE) fusion. Electrophoretic mobility shift assays demonstrated that MalE-AhyR
      specifically bound to this sequence in both the presence and absence of N
      butanoylhomoserine lactone (C4-HSL). Taken together, these data suggest that AhyR
      acts as both a negative and a positive regulator of ahyI and hence C4-HSL
      production in a growth phase dependent manner.

PMID- 15556719
TI  - Acne and sebaceous gland function.
AB  - The embryologic development of the human sebaceous gland is closely related to
      the differentiation of the hair follicle and the epidermis. The number of
      sebaceous glands remains approximately the same throughout life, whereas their
      size tends to increase with age. The development and function of the sebaceous
      gland in the fetal and neonatal periods appear to be regulated by maternal
      androgens and by endogenous steroid synthesis, as well as by other morphogens.
      The most apparent function of the glands is to excrete sebum. A strong increase
      in sebum excretion occurs a few hours after birth; this peaks during the first
      week and slowly subsides thereafter. A new rise takes place at about age 9 years
      with adrenarche and continues up to age 17 years, when the adult level is
      reached. The sebaceous gland is an important formation site of active androgens.
      Androgens are well known for their effects on sebum excretion, whereas terminal
      sebocyte differentiation is assisted by peroxisome proliferator-activated
      receptor ligands. Estrogens, glucocorticoids, and prolactin also influence
      sebaceous gland function. In addition, stress-sensing cutaneous signals lead to
      the production and release of corticotrophin-releasing hormone from dermal nerves
      and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar
      lipids. Among other lipid fractions, sebaceous glands have been shown to
      synthesize considerable amounts of free fatty acids without exogenous influence.
      Sebaceous lipids are responsible for the three-dimensional skin surface lipid
      organization. Contributing to the integrity of the skin barrier. They also
      exhibit strong innate antimicrobial activity, transport antioxidants to the skin
      surface, and express proinflammatory and anti-inflammatory properties. Acne in
      childhood has been suggested to be strongly associated with the development of
      severe acne during adolescence. Increased sebum excretion is a major factor in
      the pathophysiology of acne vulgaris. Other sebaceous gland functions are also
      associated with the development of acne, including sebaceous proinflammatory
      lipids; different cytokines produced locally; periglandular peptides and
      neuropeptides, such as corticotrophin-releasing hormone, which is produced by
      sebocytes; and substance P, which is expressed in the nerve endings at the
      vicinity of healthy-looking glands of acne patients. Current data indicate that
      acne vulgaris may be a primary inflammatory disease. Future drugs developed to
      treat acne not only should reduce sebum production and Propionibacterium acnes
      populations, but also should be targeted to reduce proinflammatory lipids in
      sebum, down-regulate proinflammatory signals in the pilosebaceous unit, and
      inhibit leukotriene B(4)-induced accumulation of inflammatory cells. They should
      also influence peroxisome proliferator-activated receptor regulation.
      Isotretinoin is still the most active available drug for the treatment of severe
      acne.

PMID- 15556720
TI  - Comedone formation: etiology, clinical presentation, and treatment.
AB  - An important feature in the etiology of acne is the presence of pilosebaceous
      ductal hypercornification, which can be seen histologically as microcomedones
      (Fig 1) and clinically as blackheads, whiteheads, and other forms of comedones,
      such as macrocomedones. There is a significant correlation between the severity
      of acne and the number and size of microcomedones (follicular casts), the
      presence of which is a measure of comedogenesis. This correlation can be
      demonstrated by skin surface biopsy using cyanoacrylate gel. In this procedure,
      microcomedones are sampled by applying cyanoacrylate gel to the skin surface. A
      glass microscopic slide is then applied on top of the gel and pressed firmly onto
      the skin for 1 minute(1-3). The glass slide is gently removed, taking with it the
      upper part of the stratum corneum and microcomedones, which are then analyzed by
      low-power microscopy or digital image analysis.(1-3)

PMID- 15556721
TI  - Acne and Propionibacterium acnes.
AB  - The involvement of microorganisms in the development of acne has a long and
      checkered history. Just over 100 years ago, Propionibacterium acnes (then known
      as Bacillus acnes) was isolated from acne lesions, and it was suggested that P.
      acnes was involved in the pathology of the disease. The 1960s saw the use of
      antibiotics to treat acne, and the consequent clinical success combined with
      reductions in P. acnes gave new impetus to the debate. Over the past two decades,
      the inevitable emergence of antibiotic-resistant strains of P. acnes as a
      consequence of acne therapy not only has reopened the debate as to the role of P.
      acnes in acne, but also has created some serious health care implications.

PMID- 15556722
TI  - Acne: inflammation.
AB  - The inflammatory stage of acne vulgaris is usually of greatest concern to the
      patient. A number of morphologically different inflammatory lesions may form that
      can be painful and unsightly. In 30% of patients, such lesions lead to
      scarring(1). Inflammatory acne and acne scarring can have significant
      psychological effects on the patient, including depression, anxiety, and poor
      self-image(2). Although inflammatory acne has been well characterized clinically,
      the mechanisms by which inflammatory lesions arise are still poorly understood.
      The human skin commensal bacterium, Propionibacterium acnes, has long been
      associated with inflammatory acne. This organism has been implicated over and
      above all of the other cutaneous microflora in contributing to the inflammatory
      response characteristic of acne. However, its precise role in the disease and its
      interaction with the human immune system remain to be elucidated.

PMID- 15556723
TI  - Acne: clinical presentations.
AB  - Acne vulgaris, the most common disease of the skin, can be manifested in a wide
      variety of clinical presentations. As a result of this clinical variation, there
      are almost as many classifications of acne as there are clinicians with
      particular interest in the disease. Thus acne has been classified as types I-IV,
      inflammatory versus noninflammatory, comedonal, comedopapular, papular,
      papulopustular, pustular, and "cystic" or nodular (even nodular-cystic). For
      those who are enamored of classification, there are subdivisions of the various
      categories, including "sandpaper comedones" and microcysts. There is even
      disagreement as to what constitutes a papule versus a nodule. The classic
      textbook definition of a nodule refers to lesions 1 cm or larger, but the early
      investigators of oral isotretinoin defined nodules as 4 mm or larger, and this
      definition has creeped into many texts, recently clarified by Bologna.(1)

PMID- 15556724
TI  - Acne and diet.
AB  - Forbidden foods? "The first law of dietetics seems to be: If it tastes good, it's
      bad for you" (Isaac Asimov, Russian-born biochemist and science fiction writer).
      This was essentially the Magna Carta for dermatologists of the 1950s: anything
      coveted by the teenage palate was suspect for morning after acne. Today, half a
      century later, although the slant has shifted away for this line of thinking in
      our dermatologic textbooks, several articles on the beliefs and perceptions of
      acne patients showed that nothing much has changed and that they expect us to
      give them detailed instructions of what "acne-related" foods they should avoid.
      In one such study(1), diet was the third most frequently implicated factor (after
      hormones and genetics) as the cause of the disease, with 32% of the respondents
      selecting diet as the main cause, and 44% thinking that foods aggravate acne. In
      another study that analyzed knowledge about causes of acne among English
      teenagers, 11% of the responders blamed greasy food as the main cause of the
      disease(2), whereas in another study found that 41% of final-year medical
      students of the University of Melbourne chose diet as an important factor of acne
      exacerbation on a final examination.(3)

PMID- 15556725
TI  - The assessment of acne: an evaluation of grading and lesion counting in the
      measurement of acne.
AB  - The basic morphology of acne--comedones, papules, pustules, and nodules--and the
      extent of involvement do not permit simple evaluation due to the number of
      variables involved. Because these acne lesions may vary in number during the
      natural course of the disease, various measurements have been developed, based on
      clinical examination and photographic documentation. These range from global
      assessments to lesion counting, with the latter providing more objective data.

PMID- 15556726
TI  - Acne: topical treatment.
AB  - Acne vulgaris is a common skin disease, affecting about 70-80% of adolescents and
      young adults. It is a multifactorial disease of the pilosebaceous unit.(1) The
      influence of androgens at the onset of adolescence leads to an enlargement of the
      sebaceous gland and a rise in sebum production. Additional increased
      proliferation and altered differentiation of the follicular epithelium eventually
      blocks the pilosebaceous duct, leading to development of the microcomedo as the
      primary acne lesion. Concomitantly and subsequently, colonization with
      Propionibacterium acnes increases, followed by induction of inflammatory
      reactions from bacteria, ductal corneocytes, and sebaceous proinflammatory agents
      (Fig 1).(2-5)

PMID- 15556727
TI  - Comparison of topical retinoids in the treatment of acne.
AB  - Topical retinoids are been used to successfully treat acne for almost 3 decades.
      At the beginning, a retinoid was a compound of similar structure and action to
      retinol (vitamin A).(1) Changes at the carboxylic end group, the polyene chain,
      and the aromatic ring can result in the modification of the original molecule. To
      date, three generations of retinoids have been developed: the nonaromatics
      (retinol, tretinoin, and isotretinoin), the monoaromatics (etretinate and
      acitretin), and the polyaromatics (arotinoid, adapalene, and tazarotene). The new
      synthetic retinoid molecules have little resemblance with retinol but nonetheless
      are included in this family because they have the ability to bind with or
      activate retinoid receptors. Therefore, retinoids are vitamins and also
      hormones.(3)

PMID- 15556728
TI  - Acne: systemic treatment.
AB  - Acne vulgaris is a disease affecting mostly adolescents and young adults that,
      when severe, has the potential to result in scarring and permanent disfigurement.
      Systemic treatment is necessary to prevent significant psychological and social
      impairment in these patients.(1) Significant inflammatory and nodulocystic acne
      is usually recalcitrant to topical treatment, whereas uncommon acne variants,
      such as acne fulminans, pyoderma faciale, and acne conglobata, need to be
      promptly and effectively controlled. In all of these circumstances, systemic
      agents are indispensable. The choices include oral antibiotics, isotretinoin, and
      hormonal treatment (Table 1).

PMID- 15556729
TI  - Acne: hormonal concepts and therapy.
AB  - Acne vulgaris is the most common skin condition observed in the medical
      community. Although we know that hormones are important in the development of
      acne, many questions remain unanswered regarding the mechanisms by which hormones
      exert their effects. Androgens such as dihydrotestosterone (DHT) and
      testosterone, the adrenal precursor dehydroepiandrosterone sulfate (DHEAS),
      estrogens such as estradiol, and other hormones, including growth hormone and
      insulin-like growth factors (IGFs), may be important in acne. It is not known
      whether these hormones are taken up from the serum by the sebaceous gland,
      whether they are produced locally within the gland, or whether a combination of
      these processes is involved. Finally, the cellular and molecular mechanisms by
      which these hormones exert their influence on the sebaceous gland have not been
      fully elucidated. Hormonal therapy is an option in women with acne not responding
      to conventional treatment or with signs of endocrine abnormalities.

PMID- 15556730
TI  - Acne: physical treatment.
AB  - Different physical treatments may be used in acne therapy. The main indications
      are for treating retentional lesions (open and comedones), inflamed lesions, and
      scars.

PMID- 15556731
TI  - Acne: treatment of scars.
AB  - Acne is a common disease affecting a significant proportion of the population.(1
      3) It causes considerable morbidity through soreness, disfigurement, and social
      handicap due to inflammatory lesions.(4,5) Modern therapy ensures that a
      considerable proportion of all patients can be offered effective treatment of
      their disease, but the morbidity is not restricted solely to the inflammatory
      lesions of acne.(6,7) Despite appropriate and effective primary prevention of
      scarring, scarring occurs in some degree in 95% of all patients irrespective of
      the severity of inflammatory acne (although severe acne causes more scarring than
      the milder forms). The scarring causes long-term morbidity that requires specific
      therapy.(7)

PMID- 15556732
TI  - Guidelines for treating acne.
AB  - Acne, a chronic inflammatory disease of the pilosebaceous units of the face,
      neck, chest, and back, is the most common skin disorder occurring universally,
      with an estimated prevalence of 70-87%.(1) It is a pleomorphic disorder
      characterized by both inflammatory (papules, pustules, nodules) and
      noninflammatory (comedones, open and closed) lesions. Grading of acne is
      mandatory to determine the appropriate therapeutic strategy. Mild acne can be
      purely comedonal or mild papulopustular, with a few papulopustules present as
      well.(2) Moderate acne is characterized by numerous comedones, few to many
      pustules, and few small nodules, with no residual scarring.(2) In severe acne
      papulopustules are numerous, many nodules can be detected, inflammation is
      marked, and scarring is present.(2) Very severe acne can be recognized by sinus
      tracts, grouped comedones, many deeply located nodules, and severe inflammation
      and scarring.(2) Although acne does not affect health overall, its impact on
      emotional well-being and function can be critical and is often associated with
      depression, anxiety, and higher-than-average unemployment rates.(3) Effective
      treatment can dramatically improve a person's quality of life.

PMID- 15556734
TI  - Motorcycle-related hospitalizations in the United States, 2001.
AB  - OBJECTIVES: To estimate the prevalence of motorcycle-related hospitalization in
      the United States in 2001 and to describe the demographic, clinical, hospital,
      and financial characteristics associated with these injuries. METHODS: Cross
      sectional analysis of the 2001 Nationwide Inpatient Sample of the Healthcare Cost
      and Utilization Project was conducted in 2003. RESULTS: There were an estimated
      30,505 (confidence interval=26,566-34,445) motorcycle-related hospital discharges
      in 2001. Approximately 62% of cases were aged > or =30 years, and males accounted
      for 89% of cases. The most common principal diagnoses were fractures of the lower
      limb (29.4%), fractures of the upper limb (13.1%), and intracranial injuries
      (12.3%). The mean length of stay was 5 days, the median hospital charge was
      $15,404, and the total estimated hospital charges were >$841 million. The
      majority of patients (56.5%) were admitted to large urban teaching hospitals, and
      these hospitals accounted for nearly 70% of all hospital charges. Approximately
      26% of cases were self-pay or listed public insurance as the expected payer.
      CONCLUSIONS: These findings shed light on the substantial morbidity and financial
      impact of motorcycle-related injuries. Renewed and strengthened prevention
      efforts are warranted.

PMID- 15556735
TI  - Where there's smoke there's money: tobacco industry campaign contributions and
      U.S. Congressional voting.
AB  - BACKGROUND: Tobacco use is the leading preventable cause of death in the United
      States. A direct contributor to this massive health burden is the effectiveness
      of the tobacco industry's activities, including campaign contributions. METHODS:
      Voting records of 527 members of the 106th U.S. Congress were obtained for 49
      tobacco-related bills between 1997 and 2000. Tobacco industry political action
      committee (PAC) contributions for each member were summed from 1993 to 2000. A
      cross-sectional, multilevel model was constructed that predicts voting behavior
      based on amount of contributions, political party, home state, and amount of
      state tobacco agriculture. The data were analyzed in 2002, 2003, and 2004.
      RESULTS: A total of $6,827,763 was received by the legislators from 17 tobacco
      industry PACs, an average of $12,956 per member. Senate Republicans received the
      most money (mean $22,004), while Senate Democrats received the least ($6,057).
      Republicans voted pro-tobacco 73% of the time and Democrats voted pro-tobacco
      only 23% of the time (p <0.001). Pro-tobacco voting percentage varied
      significantly by state (intraclass correlation coefficient=0.27, p <0.001). The
      amount of PAC money received by a member of Congress was positively associated
      with voting pro-tobacco (p <0.01), even after controlling for political party,
      state, and state tobacco farming. For Democrats in Congress who voted pro
      tobacco, for every $10,000 contribution they received, they were 9.8% more likely
      to do so. On the other hand, for Republicans who voted pro-tobacco, for every
      $10,000 received, they were only 3.5% more likely to do so. CONCLUSIONS: Tobacco
      industry contributions, political party, and state-level factors influence the
      voting behavior of Congress members. In the 106th Congress, Republicans voted pro
      tobacco over three times as often as Democrats. However, for those Democrats who
      voted pro-tobacco, the relationship between receiving tobacco industry PAC money
      and a pro-tobacco vote was stronger than it was for Republicans.

PMID- 15556736
TI  - Comorbidity and early diagnosis of head and neck cancer in a Medicare population.
AB  - BACKGROUND: This study assessed potential opportunities for an early diagnosis of
      head and neck cancers (HNCA), and the role played by comorbidity, among contacts
      by Medicare patients with the healthcare system before their diagnosis.
      Comorbidity was hypothesized to affect the relationship between use of healthcare
      services and stage of disease. METHODS: The study database (n =11,312) was
      constructed by linking files from the Surveillance, Epidemiology, and End Results
      Program 1991 through 1999 and those of the Center for Medicare and Medicaid
      Services Program. HNCA cases were comprised of the lip, oral cavity, pharynx, and
      larynx anatomic sites. RESULTS: Among persons with no alcohol and tobacco-related
      comorbidities (ATC), increasing numbers of physician visits were independently
      associated with a reduced risk of advanced stage at diagnosis for all anatomic
      sites, but especially the pharynx and larynx. Among persons with one or more ATC,
      physician visits displayed no association with stage at diagnosis with the
      exception of laryngeal tumors, where physician visits were strongly associated
      with reduced risk of late stage at diagnosis. Over 46% of cases with advanced
      stage tumors, most of whom also had ATC disease, had > or =11 physician visits in
      the year preceding their diagnosis of HNCA. CONCLUSIONS: Potential opportunities
      for an earlier diagnosis of HNCA were found among the numerous contacts with the
      healthcare system that patients had prior to their cancer diagnosis. Such
      opportunities were especially numerous and relevant for persons with ATC and form
      the basis for combining high-risk with opportunistic screening approaches.

PMID- 15556737
TI  - Child maltreatment in Missouri: combining data for public health surveillance.
AB  - BACKGROUND: Public health surveillance was established for nonfatal child
      maltreatment in Missouri using two data sources. This paper describes the
      epidemiology of nonfatal child maltreatment using this surveillance system, and
      assesses the usefulness of combining medical data with child protective services
      (CPS) reports for child maltreatment surveillance. METHODS: Child abuse and
      neglect reports for children aged <10 years for 2000 were obtained from the
      Missouri Division of Family Services (DFS) and linked to hospital discharge and
      emergency department (ED) data for 2000. Children were classified as maltreated
      if they had an International Classification of Disease (ICD) maltreatment code
      for a hospital or ED visit, or a substantiated report to DFS. Validity of the ICD
      maltreatment codes was assessed in a 10% random sample of the hospital/ED visits.
      Medical records were reviewed to determine the accuracy of the maltreatment code
      assigned. The data analyses reported here were conducted in 2002 and 2003.
      RESULTS: In the linked data, 5657 children met the case definition of
      maltreatment, providing a nonfatal maltreatment rate of 7.4/1000 children. Rates
      were higher among children aged <1 year (8.4/1000), females (7.7/1000), African
      Americans (11.8/1000), and children residing in rural counties (8.7/1000). The
      hospital/ED data identified proportionately more children who were African
      American, urban, physically abused, or infants, and uniquely identified only 10%
      of the total cases. In the validation sample, maltreatment was documented in 110
      (87%) of the 127 records reviewed. CONCLUSIONS: CPS and medical data can be
      linked for surveillance. However, the medical data add few unique cases and
      identify only a subset of maltreated children.

PMID- 15556738
TI  - A comprehensive examination of health conditions associated with obesity in older
      adults.
AB  - BACKGROUND: Over 70% of older adults in the United States are overweight or
      obese. To examine the overall health burden of obesity in older adults, the
      Vitamins and Lifestyle cohort study of western Washington State recruited 73,003
      adults aged 50 to 76 who completed a self-administered questionnaire on current
      height and weight, medical history, and risk factors. METHODS: Cross-sectional
      analysis of body mass index (BMI) and health conditions was performed using data
      collected in 2000 to 2002. Participants were categorized as normal weight,
      overweight, obese I, or obese II/III using BMI cut-points. Health conditions
      included 7 serious diseases, 2 conditions associated with cardiovascular disease
      risk, 23 medical conditions, and 11 health complaints. Odds ratios (ORs) from
      logistic regression models were used to examine associations of the four BMI
      categories with each health condition. Analyses were gender stratified and
      adjusted for age, education, race/ethnicity, and smoking status. RESULTS: Among
      women, 34% were overweight, 16% in the obese I category, and 10% in obese
      categories II/III. Among men, 49% were overweight, 18% in the obese I category,
      and 6% in obese categories II/III. Overall, 37 of 41 conditions examined for
      women and 29 of 41 conditions examined for men were associated with increased
      levels of BMI (trend p <0.05 for all models). For women and men, respectively,
      the highest ORs comparing obese II/III to normal weight were diabetes (OR=12.5
      and 8.3), knee replacement (OR=11.7 and 6.1), and hypertension (OR=5.4 and 5.6).
      Obesity also increased the odds of several rare diseases such as pancreatitis
      (OR=1.9 and 1.5) and health complaints such as chronic fatigue (OR=3.7 and 3.5)
      and insomnia (OR=3.5 and 3.1). CONCLUSIONS: A broad range of diseases and health
      complaints are associated with obesity. Clinicians should be aware of the diverse
      ways in which being overweight or obese may affect the health of their patients
      when counseling them about weight loss.

PMID- 15556739
TI  - Family history as a risk factor for stroke in young women.
AB  - BACKGROUND: Family history of stroke (FHS) is associated with risk of stroke in
      middle-aged to elderly populations. However, few studies have examined this
      association in younger women or by stroke type. A population-based, case-control
      study was conducted to examine the association of FHS and risk of stroke in young
      women, and to determine whether the association is independent of other stroke
      risk factors. METHODS: Cases were women aged 18 to 44 years, with first, nonfatal
      ischemic (n =49) and hemorrhagic (n = 63) strokes in western Washington State in
      1991 to 1995. Demographically similar community controls (n = 446) were
      identified through random-digit telephone dialing. Information on FHS in first
      degree relatives (parents and siblings) and other risk factors was obtained
      through an interview. Person-years (P-Y) at risk of stroke for relatives of each
      subject were included in polytomous logistic regression models to adjust for
      family size. The analysis was conducted between 1999 and 2000. RESULTS: After
      adjustment for age and P-Y, FHS in first-degree relatives was significantly
      associated with an increased risk of hemorrhagic (odds ratio [OR]=2.6, 95%
      confidence interval [CI]=1.5-4.3) and ischemic stroke (OR=2.1, 95% CI=1.2-3.9).
      FHS remained associated with risk of hemorrhagic stroke (OR=2.4, 95% CI=1.4-4.1)
      and ischemic stroke (OR=1.8, 95%CI=0.9-3.5) after further adjustment for
      diabetes, hypertension, hypercholesterolemia, body mass index, physical activity,
      smoking, alcohol, and family history of myocardial infarction. Findings were
      similar when associations with parental and sibling FHS were examined separately.
      CONCLUSIONS: Family history of stroke is a risk factor for both hemorrhagic and
      ischemic strokes among young women.

PMID- 15556740
TI  - Feasibility of influenza immunization for inner-city children aged 6 to 23
      months.
AB  - BACKGROUND: Annual influenza-related hospitalization rates of children aged < 2
      years in the United States are second only to those of the elderly. Yet no
      recommendations existed for vaccinating healthy children aged 6 to 23 months
      until 2002, when the Advisory Committee on Immunization Practices encouraged
      influenza vaccination for them. This study tested the feasibility of vaccinating
      6- to 23-month-old children against influenza and assessed the effect on timely
      receipt of other vaccines. METHODS: A pre-post trial was used in urban health
      centers serving low-income children. Sites selected interventions from strategies
      proven to increase vaccination rates. Targeted patients were aged 6 to 23 months
      by November 30, 2002 (N = 1534). RESULTS: Influenza vaccination rates for the
      2002-2003 intervention season improved significantly from 6.5% to 38.5% for the
      first dose (p < 0.001). Second-dose rates were significantly improved over
      preintervention (1.9% preintervention, 13.2% intervention), but lower than first
      dose rates. Mean ages at vaccination for other recommended childhood vaccines did
      not differ or were significantly younger (measles, mumps, and rubella vaccine
      [MMR] and varicella) for children who received influenza vaccine versus those who
      did not. Moreover, a higher percentage of influenza-vaccinated than unvaccinated
      children received MMR, diphtheria, tetanus, pertussis vaccine 3 (DTaP3),
      inactivated poliovirus vaccine 2 (IPV2), and Haemophilus influenzae b (Hib2)
      vaccines within a 2-month grace period of the recommended age (p < 0.039), with
      no differences between groups for Hib1, DTaP1, IPV1, and varicella. CONCLUSIONS:
      With directed effort, it is possible to increase influenza vaccination at health
      centers serving low-income children. The addition of a two-dose vaccine was not
      associated with delayed receipt of other vaccines among these children.

PMID- 15556741
TI  - Health risk factors among detained adolescent females.
AB  - OBJECTIVES: To identify the prevalence of health risk factors among a sample of
      detained adolescent females and determine whether there are racial/ethnic
      differences. DESIGN AND SETTING: A cross-sectional survey of 197 adolescent
      females (aged 14 to 18 years) recruited within eight detention facilities.
      OUTCOME MEASURES: Thirty-five measures, comprising four domains, were assessed.
      Domains were sex-related risk factors, violence-related risk factors, selected
      mental health issues, and substance abuse behaviors. Measures were collected
      using audio-computer-assisted self-interviewing. A biological assessment for the
      presence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas
      vaginalis was also conducted. RESULTS: Several health risk factors were
      especially prominent. Mean age of sexual debut was 13 years. The mean number of
      sex partners (lifetime) was 8.8. Twenty percent tested positive for an STD, and
      32.2% had ever been pregnant. Of those reporting sexual activity, 33.9% had not
      used any form of contraception in the past 2 months and about 40% reported having
      recent sex with a casual partner. More than 40% reported that a friend had been
      beaten, attacked, or hurt by others in the past year. More than one half had
      witnessed violence (past year) and nearly 30% had ever belonged to a gang. Forty
      percent had thought about committing suicide in the past 2 months, with 35%
      informing someone of their intent, and 25% attempting suicide. Recent use of
      illegal substances was common. Correlations between the four domains were
      significant (p < 0.03), but weak. With some notable exceptions (STD prevalence,
      trading sex for money, witnessing violence), no difference was found between
      minority and nonminority adolescents with respect to risk factors. After creating
      an index of all the risk factors, a normal distribution was obtained (mean number
      of factors, 10.3; standard deviation, 5.0). CONCLUSIONS: Preventive medicine
      programs for adolescent females within detention facilities are warranted. Our
      evidence suggests that health risk behaviors in this population may be quite
      diverse; therefore, these programs should be broad in scope and that depth of the
      programs should vary as a function of risk level.

PMID- 15556742
TI  - Implementing guidelines for smoking cessation: comparing the efforts of nurses
      and medical assistants.
AB  - BACKGROUND: It is unclear how different types of intake clinicians (registered
      nurses [RNs], and less costly licensed practical nurses [LPNs] and medical
      assistants [MAs]) compare in the performance of smoking-cessation activities
      recommended in the Agency for Healthcare Research and Quality (AHRQ) smoking
      cessation clinical practice guideline. METHODS: A secondary analysis of data from
      a randomized controlled trial of guideline implementation was performed. Exit
      interviews of consecutive adult smokers who presented to nine primary care
      clinics for routine, non-emergency care were conducted during the period February
      2000 to May 2001; a total of 1221 patients with adequate data were analyzed.
      Intake clinicians were surveyed prior to guideline training. Hierarchical
      logistic regression models were used to determine the association between type of
      intake clinician and performance of cessation counseling at the clinic visit,
      after adjustment for patient-level covariates, intake clinicians'
      characteristics, and study site. RESULTS: Performance of all guideline
      recommended counseling activities were significantly greater for all intake
      clinicians at test versus control sites. MAs were significantly less likely to
      assess willingness to quit (adjusted odds ratio [AOR]=0.4, 95% confidence
      interval [CI]=0.2-0.8, p =0.005) and tended to offer advice and assistance in
      quitting less often than RNs. Similar findings were observed for LPNs (AOR=0.5,
      95% CI=0.3-1.0, p =0.03, for assessing willingness to quit). Subset analysis in
      subjects with complete survey data revealed that being seen by a MA was no longer
      associated with statistically significant differences in performance, after
      accounting for personal beliefs, self-efficacy, and role satisfaction in
      cessation counseling. CONCLUSIONS: Although both MAs and LPNs showed marked
      improvements in performance in response to the guideline intervention, patients
      seen by these intake clinicians were less likely to receive guideline-recommended
      counseling, compared to those patients seen by RNs. Given their important role in
      the delivery of preventive care, MAs and LPNs should receive proper training in
      cessation counseling, should have strong physician and administrative support,
      and should be included in efforts to implement smoking-cessation guidelines in
      primary care.

PMID- 15556743
TI  - Evidence-based public health: an evolving concept.
AB  - Evidence-based public health (EBPH) has been proposed as a practice model that
      builds upon the success of evidence-based medicine (EBM). EBM has been described
      as a more scientific and systematic approach to the practice of medicine. It has
      enhanced medical training and practice in many settings. Both EBM and EBPH
      systematically use data, information, and scientific principles to enhance
      clinical care and population health, respectively. In this paper, we review the
      evolution of EBPH, propose a new definition for EBPH, and discuss developments
      that may support its further advancement.

PMID- 15556744
TI  - Interventions to prevent skin cancer by reducing exposure to ultraviolet
      radiation: a systematic review.
AB  - The relationship between skin cancer and ultraviolet radiation is well
      established. Behaviors such as seeking shade, avoiding sun exposure during peak
      hours of radiation, wearing protective clothing, or some combination of these
      behaviors can provide protection. Sunscreen use alone is not considered an
      adequate protection against ultraviolet radiation. This report presents the
      results of systematic reviews of effectiveness, applicability, other harms or
      benefits, economic evaluations, and barriers to use of selected interventions to
      prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force
      on Community Preventive Services found that education and policy approaches to
      increasing sun-protective behaviors were effective when implemented in primary
      schools and in recreational or tourism settings, but found insufficient evidence
      to determine effectiveness when implemented in other settings, such as child care
      centers, secondary schools and colleges, and occupational settings. They also
      found insufficient evidence to determine the effectiveness of interventions
      oriented to healthcare settings and providers, media campaigns alone,
      interventions oriented to parents or caregivers of children, and community-wide
      multicomponent interventions. The report also provides suggestions for areas for
      future research.

PMID- 15556745
TI  - Recommendations to prevent skin cancer by reducing exposure to ultraviolet
      radiation.

PMID- 15556746
TI  - Clinical prevention and population health: curriculum framework for health
      professions.
AB  - The Clinical Prevention and Population Health Curriculum Framework is the initial
      product of the Healthy People Curriculum Task Force convened by the Association
      of Teachers of Preventive Medicine and the Association of Academic Health
      Centers. The Task Force includes representatives of allopathic and osteopathic
      medicine, nursing and nurse practitioners, dentistry, pharmacy, and physician
      assistants. The Task Force aims to accomplish the Healthy People 2010 goal of
      increasing the prevention content of clinical health professional education. The
      Curriculum Framework provides a structure for organizing curriculum, monitoring
      curriculum, and communicating within and among professions. The Framework
      contains four components: evidence base for practice, clinical preventive
      services-health promotion, health systems and health policy, and community
      aspects of practice. The full Framework includes 19 domains. The title "Clinical
      Prevention and Population Health" has been carefully chosen to include both
      individual- and population-oriented prevention efforts. It is recommended that
      all participating clinical health professions use this title when referring to
      this area of curriculum. The Task Force recommends that each profession
      systematically determine whether appropriate items in the Curriculum Framework
      are included in its standardized examinations for licensure and certification and
      for program accreditation.

PMID- 15556747
TI  - Why a clinical prevention and population health curriculum framework?

PMID- 15556748
TI  - Healthy people curriculum task force: a commentary by the surgeon general.

PMID- 15556749
TI  - Clinical prevention and population health: getting there from here.

PMID- 15556750
TI  - Skin cancer prevention: a commentary.

PMID- 15556751
TI  - Skin cancer prevention comes of age.

PMID- 15556752
TI  - Corticosteroids: the mainstay in asthma therapy.
AB  - Inflammation is now marked as a central feature of asthma pathophysiology and
      aims of current asthma management are not only to treat acute symptoms of
      wheezing, breathlessness, chest tightness, cough but also to suppress the
      underlying inflammatory component. Despite the availability of a number of drugs,
      corticosteroids remain the mainstay in the management of all types of asthma as
      these are the most potent and effective antiinflammatory agents available so far.
      Corticosteroids suppress virtually every step in inflammation. However
      therapeutic doses of oral glucocorticoids are associated with a range of adverse
      reactions. To overcome these side effects, inhalations have been developed to
      deliver glucocorticoids directly to the lungs and in the process a number of
      aerosol preparations have become available, which have advantage of significantly
      lower toxicity due to low systemic absorption from the respiratory tract and
      rapid inactivation. Despite considerable efforts by pharmaceutical industry, it
      has been difficult to develop novel therapeutic agents for asthma management,
      which could surpass inhaled corticosteroids. Currently the data favours using
      inhaled corticosteroids as monotherapy in the majority of patients in all kinds
      of asthma. If combination therapy is recommended to achieve additional control in
      severe asthma cases, other drugs such as beta-agonists, antileukotrienes,
      theophylline, etc. are considered as adjunct therapies to corticosteroids. This
      review discusses the importance of corticosteroids as first line therapy for
      asthma treatment with the availability of inhaled corticosteroids for chronic
      treatment and oral formulations for treating acute exacerbations of moderate to
      severe asthma.

PMID- 15556753
TI  - Synthesis of a biotin-conjugate of phosmidosine O-ethyl ester as a G1 arrest
      antitumor drug.
AB  - This paper deals with the synthesis of a stable biotin-phosmidosine conjugate
      molecule 3 that is required for isolation of biomolecules that bind to
      phosmidosine (1). It was found that introduction of a biotin residue into the 6-N
      position of phosmidosine could be carried out by reaction of an N7-Boc-7,8
      dihydro-8-oxoadenosine derivative 13 with phenyl chloroformate followed by
      displacement with a diamine derivative 6 along with the simultaneous removal of
      the Boc group and one of the two phenoxycarbonyl groups and the successive
      condensation with an N-tritylated biotin derivative 5. The condensation of an N
      prolylphosphorodiamidite derivative 4 with an appropriately protected 7,8-dihydro
      8-oxoadenosine derivative 17 having the biotin residue gave the coupling product
      18, which was deprotected to give the biotin-phosmidosine (O-ethyl ester)
      conjugate 3.

PMID- 15556754
TI  - Total and local (atom and atom type) molecular quadratic indices: significance
      interpretation, comparison to other molecular descriptors, and QSPR/QSAR
      applications.
AB  - This paper describes the significance interpretation, comparison to other
      molecular descriptors, and QSPR/QSAR applications of a new set of molecular
      descriptors: atom, atom type, and total molecular quadratic indices. The features
      of the kth total and local quadratic indices are illustrated by examples of
      various types of molecular structures, including chain lengthening, branching,
      heteroatoms content, and multiple bonds. The linear independence of the local
      (atom type) quadratic indices to others 0D, 1D, 2D, and 3D molecular descriptors
      is demonstrated by using principal component analysis for 42 heterogeneous
      molecules. It is concluded that the local quadratic indices are independent
      indices containing important structural information to be used in QSPR/QSAR and
      drug design studies. In this sense, molecular quadratic indices were used to the
      description and prediction of the boiling point of 28 alkyl alcohols and to the
      modeling of the partition coefficient (logP), specific rate constant (logk), and
      antibacterial activity of 2-furylethylene derivatives. These models were
      statistically significant and showed very good stability to data variation in
      leave-one-out (LOO) cross-validation experiment. The comparison with the other
      approaches also revealed good behaviors of our method in this QSAR study.

PMID- 15556755
TI  - Active site binding modes of the beta-diketoacids: a multi-active site approach
      in HIV-1 integrase inhibitor design.
AB  - Predicting a bioactive conformation of a ligand is of paramount importance in
      rational drug design. The task becomes very difficult when the receptor site
      possesses a region with unusual conformational flexibility. Significant
      conformational differences are present in the active site regions in the
      available crystal structures of the core domains of HIV-1 integrase (IN). Among
      all reported IN inhibitors, the beta-diketoacid class of compounds has proved to
      be of most promise and indeed S-1360 was the first IN inhibitor to enter clinical
      studies. With an aim to predict the bioactive (active site bound) conformation of
      S-1360, we performed extensive docking studies using three different reported
      crystal structures where the active site or partial active site region was
      resolved. For comparison we extended our studies to include 5CITEP (the first
      compound cocrystallized with IN core domain) and a bis-diketoacid (BDKA). We
      found that the conformation of S-1360 when bound in one of the active sites
      matches that of the experimentally observed results of IN escape mutants
      resistant to S-1360. Therefore, we propose that this active site conformation is
      the biologically relevant conformation and can be used for the future structure
      based drug design studies selectively targeting IN.

PMID- 15556756
TI  - Anti-AIDS agents. Part 56: Synthesis and anti-HIV activity of 7-thia-di-O-(-)
      camphanoyl-(+)-cis-khellactone (7-thia-DCK) analogs.
AB  - Two thia-DCK analogs (3a,b) were synthesized and evaluated for inhibition of HIV
      1 replication in H9 lymphocytes. Compound 3a showed potent anti-HIV activity with
      an EC50 value of 0.14 microM and a therapeutic index of 1110. However, the
      corresponding 6-tert-butyl-substituted compound (3b) showed no suppression. The
      bioassay results indicated that thia-DCK analogs merit attention as potential HIV
      1 inhibitors.

PMID- 15556757
TI  - Synthesis and microbial inhibition study of novel 5-imidazolyl substituted
      isoxazolidines.
AB  - Cycloaddition of C-imidazolyl-N-phenylnitrones with monosubstituted alkenes
      afforded 5-imidazolyl substituted isoxazolidines with high regioselectivity.
      Novel isoxazolidines were screened for their antibacterial activities against S.
      aureus, E. coli and B. subtilis by using streptomycin as a positive control. They
      were also tested for their antifungal activities against F. moniliforme, A. niger
      and C. acremonium by using nystatin as a positive control. Isoxazolidines, 4a and
      4f exhibited more potent inhibition towards antifungal activity than the other
      isoxazolidines prepared.

PMID- 15556758
TI  - Synthesis of trehalose-based compounds and their inhibitory activities against
      Mycobacterium smegmatis.
AB  - The synthesis of a library of trehalose-based compounds has been accomplished,
      and their activities against Mycobacterium smegmatis have been determined. A
      preliminary structure-activity relationship (SAR) is reported. Despite not having
      a potent lead, one of the trehalose derivatives displays strong activity when
      applied with isoniazid (INH), which is known to have low sterilizing activity.
      The bacteriocidal nature of our compounds against Mycobacterium may be
      significant for the development of new therapies against tuberculosis.

PMID- 15556759
TI  - 3D-QSAR CoMFA, CoMSIA studies on substituted ureas as Raf-1 kinase inhibitors and
      its confirmation with structure-based studies.
AB  - Three-dimensional quantitative structure activity relationship (3D-QSAR) analyses
      were carried out on 91 substituted ureas in order to understand their Raf-1
      kinase inhibitory activities. The studies include Comparative Molecular Field
      Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA).
      Models with good predictive abilities were generated with the cross validated r2
      (r2cv) values for CoMFA and CoMSIA being 0.53 and 0.44, respectively. The
      conventional r2 values are 0.93 and 0.87 for CoMFA and CoMSIA, respectively. In
      addition, a homology model of Raf-1 was also constructed using the crystal
      structure of the kinase domain of B-Raf isoform with one of the most active Raf-1
      inhibitors (48) inside the active site. The ATP binding pocket of Raf-1 is
      virtually similar to that of B-Raf. Selected ligands were docked in the active
      site of Raf-1. Molecule 48 adopts an orientation similar to that inside the B-Raf
      active site. The 4-pyridyl group bearing amide substituent is located in the
      adenosine binding pocket, and anchored to the protein through a pair of hydrogen
      bonds with Cys424 involving ring N-atom and amide NH group. The results of best
      3D-QSAR model were compared with structure-based studies using the Raf-1 homology
      model. The results of 3D-QSAR and docking studies validate each other and
      provided insight into the structural requirements for activity of this class of
      molecules as Raf-1 inhibitors. Based on these results, novel molecules with
      improved activity can be designed.

PMID- 15556760
TI  - Chemoenzymatic synthesis of CMP-sialic acid derivatives by a one-pot two-enzyme
      system: comparison of substrate flexibility of three microbial CMP-sialic acid
      synthetases.
AB  - Three C terminal His6-tagged recombinant microbial CMP-sialic acid synthetases
      [EC 2.7.7.43] cloned from Neisseria meningitidis group B, Streptococcus
      agalactiae serotype V, and Escherichia coli K1, respectively, were evaluated for
      their ability in the synthesis of CMP-sialic acid derivatives in a one-pot two
      enzyme system. In this system, N-acetylmannosamine or mannose analogs were
      condensed with pyruvate, catalyzed by a recombinant sialic acid aldolase [EC
      4.1.3.3] cloned from E. coli K12 to provide sialic acid analogs as substrates for
      the CMP-sialic acid synthetases. The substrate flexibility and the reaction
      efficiency of the three recombinant CMP-sialic acid synthetases were compared,
      first by qualitative screening using thin layer chromatography, and then by
      quantitative analysis using high performance liquid chromatography. The N.
      meningitidis synthetase was shown to have the highest expression level, the most
      flexible substrate specificity, and the highest catalytic efficiency among the
      three synthetases. Finally, eight sugar nucleotides, including cytidine 5'
      monophosphate N-acetylneuraminic acid (CMP-Neu5Ac) and its derivatives with
      substitutions at carbon-5, carbon-8, or carbon-9 of Neu5Ac, were synthesized in a
      preparative (100-200 mg) scale from their 5- or 6-carbon sugar precursors using
      the N. meningitidis synthetase and the aldolase.

PMID- 15556761
TI  - Optimization of unique, uncharged thioesters as inhibitors of HIV replication.
AB  - A combinatorial chemistry approach was employed to prepare a restricted library
      of N-substituted S-acyl-2-mercaptobenzamide thioesters. It was shown that many
      members of this chemotype display anti-HIV activity via their ability to interact
      with HIV-1, HIV-2, SIV-infected cells, cell-free virus, and chronically and
      latently infected cells in a manner consistent with targeting of the highly
      conserved HIV-1 NCp7 zinc fingers. Compounds were initially screened using two
      different in vitro antiviral assays and evaluated for stability in neutral buffer
      containing 10% pooled human serum using a spectrophotometric assay. These data
      revealed that there was no significant correlation between thioester stability
      and antiviral activity, however, a slight inverse correlation between serum
      stability and virucidal activity was noted. Based on the virucidal capability and
      the ability to select lead compounds to inhibit virus expression from latently
      infected TNFalpha-induced U1 cells, we next determined if these compounds could
      prevent HIV cell-to-cell transmission. Several thioesters demonstrated potent
      inhibition of HIV cell-to-cell transmission with EC50 values in the 80-100 nM
      range. Thus, we have optimized a series of restricted thioesters and provided
      evidence that serum stability is not required for antiviral activity. Moreover,
      selected compounds show potential for development as topical microbicides.

PMID- 15556762
TI  - Second-generation dimeric inhibitors of chitin synthase.
AB  - Chitin synthase (CS) is essential for fungal cell wall biosynthesis and is an
      attractive medicinal target. Expanded results from our efforts to develop
      mechanism based inhibitors of CS are presented here. Specifically, we describe
      uridine dimers linked by tartrate amides as potential pyrophosphate mimics.

PMID- 15556763
TI  - Crystallographic and NMR studies of antiinfective tricyclic guanidine alkaloids
      from the sponge Monanchora unguifera.
AB  - Three tricyclic guanidine alkaloids, including 1,8a;8b,3a-didehydro-8beta
      hydroxyptilocaulin (1), 1,8a;8b,3a-didehydro-8alpha-hydroxyptilocaulin (2) and
      mirabilin B (3), were identified from the marine sponge Monanchora unguifera.
      1,8a;8b,3a-Didehydro-8alpha-hydroxyptilocaulin (2) is a new stereoisomer of 1,
      the structure of which was elucidated by spectroscopic analysis, comparison of
      its spectral data with those of 1, and confirmed by X-ray analysis. Compounds 1
      and 2 co-crystallized in an unusual perfect order and packed around an
      approximate inversion center. A mixture of 1 and 2 is active against the malaria
      parasite Plasmodium falciparum with an IC50 value of 3.8 microg/mL while
      mirabilin B (3) exhibited antifungal activity against Cryptococcus neoformans
      with an IC50 value of 7.0 microg/mL and antiprotozoal activity against Leishmania
      donovani with an IC50 value of 17 microg/mL.

PMID- 15556764
TI  - Ring-substituted quinolines. Part 2: Synthesis and antimycobacterial activities
      of ring-substituted quinolinecarbohydrazide and ring-substituted
      quinolinecarboxamide analogues.
AB  - Additional structural modifications of the new chemical entity, 2,8-dicyclopentyl
      4-methylquinoline (DCMQ; MIC=6.25 microg/mL, M. tuberculosis H37Rv) resulted in
      the synthesis of four new series of the ring-substituted quinolinecarbohydrazides
      (series 1-4) constituting 22 analogues. All new derivatives were evaluated for in
      vitro antimycobacterial activities against drug-sensitive M. tuberculosis H37Rv
      strain. Certain ring-substituted-2-quinolinecarbohydrazide analogues described
      herein showed good inhibitory activity. In particular, analogues 4-(1-adamantyl)
      2-quinolinecarbohydrazide (2d), 4,5-dicyclopentyl-2-quinolinecarbohydrazide (2e),
      4,8-dicyclopentyl-2-quinolinecarbohydrazide (2f), and 4,5-dicyclohexyl-2
      quinolinecarbohydrazide (2g) have exhibited the MIC value of 6.25 microg/mL.
      Further investigation of the most suitable lead prototype, 4-(1-adamantyl)-2
      quinolinecarbohydrazide (2d, series 1) led to the synthesis of N2-alkyl/N2,N2
      dialkyl/N2-aryl-4-(1-adamantyl)-2-quinolinecarboxamides (series 5) consisting of
      13 analogues. Some of the synthesized carboxamides 7a, 7h, and 7m reported herein
      have exhibited excellent antimycobacterial activities in the range of 6.25-3.125
      microg/mL against drug-sensitive and drug-resistant M. tuberculosis H37Rv
      strains.

PMID- 15556765
TI  - Synthesis of mono- and disaccharide analogs of moenomycin and lipid II for
      inhibition of transglycosylase activity of penicillin-binding protein 1b.
AB  - Three types of mono- and disaccharides 3a,b, 4a-c, 5, and some chaetomellic acid
      A analogs 6 and 42-44 were synthesized as potential inhibitors of the
      transglycosylase activity of penicillin-binding protein 1b (PBP1b), a key
      bacterial enzyme responsible for the formation of the polysaccharide backbone of
      peptidoglycan as well as for cross-linking of its peptide portions. The target
      compounds combine structural features of both the active portion of moenomycin
      and the natural PBP1b substrate, lipid II. The desired skeletons were obtained in
      a convergent fashion involving attachment of the lipid-alkylated glyceric acid
      moieties 11a,b to the corresponding carbohydrate-containing phosphonic acids 23,
      24a, and 24b. Compounds 3a,b were prepared to verify the distance requirements
      between the sugar and the noncleavable C-phosphonate moieties. Compounds 4a-c
      were synthesized to examine the importance of the first sugar unit of moenomycin,
      a known inhibitor of transglycosylase catalysis by PBP1b, with respect to
      antibiotic activity. These were prepared by condensation of 11a,b with 28a and
      28c, which were made by glycosylation of 3-bromopropanol with oxazolines 25a,b,
      and Arbuzov reaction with triethyl or trimethyl phosphite, followed by
      dealkylation with bromotrimethylsilane. Compound 5 was generated to verify the
      possibility of using a dicarboxylate group to mimic the diphosphate of lipid II.
      It was synthesized by coupling of alcohol 31 with alpha-trichloroacetimidate 34.
      Chaetomellic acid A analogs were prepared by a Michael addition to dimethyl
      acetylenedicarboxylate. With the exception of 3b, all of the target compounds
      were found to inhibit PBP1b, albeit with modest potency.

PMID- 15556766
TI  - Fluorescent ligands for the histamine H2 receptor: synthesis and preliminary
      characterization.
AB  - 3-[3-(Piperidinomethyl)phenoxy]alkyl, N-cyano-N'-[omega-[3-(1
      piperidinylmethyl)phenoxy]alkyl]guanidine and 2-(5-methyl-4-imidazolyl)methyl
      thioethyl derivatives containing fluorescent functionalities were synthesized and
      the histamine H2 receptor affinity was evaluated using the H2 antagonist [125I]
      aminopotentidine. The compounds exhibited weak to potent H2 receptor affinity
      with pKi values ranging from <4 to 8.85. The highest H2 receptor affinity was
      observed for N-cyano-N'-[omega-[3-(1-piperidinylmethyl)phenoxy]alkyl]guanidines
      substituted with methylanthranilate (13), cyanoindolizine (6) and cyanoisoindole
      (11) moieties via an ethyl or propyl linker.

PMID- 15556767
TI  - Synthesis and biological evaluation of new 1,5-diazaanthraquinones with cytotoxic
      activity.
AB  - A series of 1,5-diazaanthraquinone derivatives was synthesized and their in vitro
      cytotoxic activities were evaluated against several human cancer cell lines. The
      1,5-diazaanthraquinone chromophore has been synthesized either on the basis of
      hetero Diels-Alder reactions involving different quinoline-5,8-diones and
      alpha,beta-unsaturated aldehyde N,N-dimethylhydrazones or by thermolysis of
      different arylaminomethylene Meldrum's acid derivatives. Some of these compounds
      showed cytotoxic activity comparable to that of mitoxantrone against most of the
      cell lines tested. Compounds 20, 30, 31 and 37 were 4-54 times more potent that
      mitoxantrone against A549, H116, PSN1 and T98G cancer cell lines but,
      interestingly, they were 3-16 times less potent against the human breast
      carcinoma SKBR3. Some structure-activity relationships are described, the most
      significant one being the increase in cytotoxicity resulting from the
      introduction of a halogen atom at the C-4 position.

PMID- 15556768
TI  - In vitro and in vivo antimalarial activity of peptidomimetic protein
      farnesyltransferase inhibitors with improved membrane permeability.
AB  - A series of protein farnesyltransferase inhibitor ester prodrugs of FTI-2148 (17)
      were synthesized in order to evaluate the effects of ester structure modification
      on antimalarial activity and for further development of a farnesyltransferase
      inhibitor with in vivo activity. Evaluation against P. falciparum in red blood
      cells showed that all the investigated esters exhibited significant antimalarial
      activity, with the benzyl ester 16 showing the best inhibition (ED50=150 nM).
      Additionally, compound 16 displayed in vivo activity and was found to suppress
      parasitemia by 46.1% at a dose of 50 mg kg(-1) day(-1) against Plasmodium berghei
      in mice. The enhanced inhibition potency of the esters is consistent with
      improved cell membrane permeability compared to that of the free acid. The
      results of this study suggest that protein farnesyltransferase is a valid
      antimalarial drug target and that the antimalarial activity of these compounds
      derives from a balance between the hydrophobic character and the size and
      conformation of the ester moiety.

PMID- 15556769
TI  - A molecular docking study of estrogenically active compounds with 1,2
      diarylethane and 1,2-diarylethene pharmacophores.
AB  - Numerous selective estrogen receptor modulators (SERMs) have been synthesized and
      assayed in recent years. The focus of this study is to apply coarse-grain
      molecular docking procedures coupled with fine-grain all-atom force field
      optimization strategies to shed light on the binding mechanisms of currently
      available estrogen receptor-active compounds. Although the mechanics of ligand
      binding in estrogen receptors is generally well understood, there is room for
      surprises. In this paper computational evidence corroborating the experimentally
      observed type I agonistic binding mode for estradiol (E2) and diethylstilbesterol
      (DES) and the type II antagonistic binding mode for 4-hydroxytamoxifen and
      raloxifen is presented. Included in this type I agonistic mode are the DES
      derivatives, transstilbene and 1,2-diaryldiaminoethane. In addition, a novel
      'type II agonistic' binding mode for 2,3-diarylimidazolines, 4,5
      diarylimidazoles, 2,3-diarylpiperazines is introduced. This mode is stabilized by
      suggesting alternative hydrogen bond anchor points in the ligand binding domain
      as potential leads for future drug design.

PMID- 15556770
TI  - Synthesis and anticancer evaluation of certain indolo[2,3-b]quinoline
      derivatives.
AB  - The present report describes the synthesis and anticancer evaluation of certain
      11-substituted 6H-indolo[2,3-b]quinolines and their methylated derivatives. These
      6H-indolo[2,3-b]quinoline derivatives 11-13 were prepared from the commercially
      available 1,4-dihydroxyquinoline through alkylation, chlorination, nucleophilic
      reaction, and ring cyclization. Depending on the ratio of 11, (MeO)2SO2, and
      K2CO3, alkylation occurred primarily on N-5 (1:0.8:0.8) or N-6 (1:1.5:1.5)
      leading to the isolation of 14a or 14b as a major product. Accordingly, major
      product 15a (2/(MeO)2SO2/K2CO3=1:2:2) or 15b (1:1:1), respectively, was obtained
      by alkylation of 12 while 16a (13/(MeO)2SO2/K2CO3=1:2:2) or 16b (1:1:1),
      respectively, was obtained by alkylation of 13. The in vitro anticancer assay
      indicated 5-methylated derivatives 14a, 15a, 16a are more cytotoxic than their
      respective 6-methylated counterparts 14b, 15b, 16b and 6H-indolo[2,3-b]quinoline
      precursors 11, 12, 13. Among them, 11-(4-methoxyanilino)-6-methyl-6H-indolo[2,3
      b]quinoline (16a) was the most cytotoxic with a mean GI50 value of 0.78 microM
      and also exhibited selective cytotoxicities for HL-60 (TB), K-562, MOLT-4, RPMI
      8226, and SR with GI50 values of 0.11, 0.42, 0.09, 0.14, and 0.19 microM,
      respectively.

PMID- 15556771
TI  - Design, synthesis, and inhibition of platelet aggregation for some 1-o
      chlorophenyl-1,2,3,4-tetrahydroisoquinoline derivatives.
AB  - Based on ticlopidine active as an ADP receptor antagonist for inhibiting platelet
      aggregation in clinical test, and upon finding (+/-)-1,2-substituted-7
      sulfonylamide/amide-1,2,3,4-tetrahydroisoquinoline (11-31) inhibited of platelet
      aggregation, a series of (+/-)-1-o-chlorophenyl-2-substituted
      tetrahydroisoquinoline derivatives was designed and synthesized. Four analogs
      proved to be potential antiplatelet aggregation agents, and compound 9 (TQP-3,
      applying for patent) which inhibits ADP-induced human platelet aggregation with
      IC50 values of approximately 0.206 nM was the most active. Compound 2 is more
      active than compound 1, which (Type I) is similar to ticlopidine. This is because
      there is a spacial hindrance in compound 1, and the o-chloro group of compound 2
      may play the same a role as o-chloro group of ticlopidine. On the other hand,
      with the different substitutions at different positions on the 2-substituted
      phenylacyl group, their inhibition of platelet aggregation differs. These
      compounds with m-substituted group (5, 7, 9) showed a higher IC50 value for
      inhibiting ADP-induced human platelet aggregation than those with o-substituted
      group (4, 6) or p-substituted group (3, 8). It was observed that their inhibition
      is bromine-substituted derivative (9), chlorine-substituted derivative (7), and
      nitro-substituted derivative (5) in turn. Moreover, these compounds (Type II) may
      be more similar to clopidogrel than to ticlopidine due to the acyl group at 2
      position of the nucleus playing a role as the ester group of clopidogrel. It was
      conjectured that these analogs function as a potential antiplatelet aggregation
      role by acting as ADP receptor antagonists.

PMID- 15556772
TI  - Design, synthesis, computational and biological evaluation of new anxiolytics.
AB  - New anxiolytics have been discovered by prediction of biological activity with
      computer programs pass and derek for a heterogeneous set of 5494 highly
      chemically diverse heterocyclic compounds (thiazoles, pyrazoles, isatins, a-fused
      imidazoles and others). The majority of tested compounds exhibit the predicted
      anxiolytic effect. The most potent activity was found in 2-(4-nitrophenyl)-3-(4
      phenylpiperazinomethyl)imidazo[1,2-a]pyridine 8, 1-[(4-bromophenyl)-2-oxoethyl]-3
      (1,3-dioxolano)-2-indolinone 3, 5-hydroxy-3-methoxycarbonyl-1-phenylpyrazole 5
      and 2-(4-fluorophenyl)-3-(4-methylpiperazinomethyl)imidazo[1,2-a]pyridine 7. The
      application of the computer-assisted approach significantly reduced the number of
      synthesized and tested compounds and increased the chance of finding new chemical
      entities (NCEs).

PMID- 15556773
TI  - Synthesis and glycosidase inhibitory activity of some N-substituted 5a-carba-beta
      fuco- and beta-galactopyranosylamines, and selected derivatives.
AB  - In the course of chemical modification of alpha-fucosidase inhibitors of 5a-carba
      fucopyranosylamine type, an N-dodecyl derivative of the enantiomer 6-deoxy-5a
      carba-beta-D-galactopyranosylamine demonstrated very strong inhibition of beta
      galactosidase and beta-glucosidase. This finding led us to synthesize
      corresponding 6-hydroxy compounds, in order to elucidate structure-activity
      relationships for inhibitors of this type. Among four N-alkyl-5a-carba-beta-D
      galactopyranosylamines prepared, the N-octyl derivative could be demonstrated to
      possess moderate activity toward alpha- and beta-galactosidases, and beta
      glucosidase.

PMID- 15556774
TI  - Thermal stability of triple helical DNAs containing 2'-deoxyinosine and 2'
      deoxyxanthosine.
AB  - In this paper, we describe the synthesis and thermal stabilities of the triplexes
      containing either 2'-deoxyinosine (1) or 2'-deoxyxanthosine (3) in their second
      strands. It was found that the triplexes with the 2'-deoxy-5
      methylcytidine(dM)*1:dC and dM*1:dA base triplets are thermally stable, but those
      containing the dM*1:T and dM*1:dG base triplets are unstable under both neutral
      and slightly acidic conditions. On the other hand, it was found that the
      oligonucleotide containing 3 could form thermally stable triplexes with the
      oligonucleotides that involve four natural bases opposite the sites of 3. The
      rank of the thermal stabilities of the triplexes was as follows: the triplex
      containing the dM*3:dC base triplet > that containing the dM*3:dA base triplet >
      that containing the dM*3:T base triplet > that containing the dM*3:dG base
      triplet.

PMID- 15556775
TI  - Proinflammatory parameters as CRP and IL-6 do not discriminate between post-PCI
      cardiac patients with and without exercise-induced ischemia as indicated by Tl
      201 myocardial scintigraphy.
AB  - INTRODUCTION: Atherosclerosis is looked upon as an inflammatory disease. The
      production of proinflammatory markers may indicate activity in this inflammatory
      state. METHODS: We prospectively evaluated a range of proinflammatory serum
      parameters in 136 cardiac patients who had previously undergone percutaneous
      coronary intervention (PCI). RESULTS: By means of myocardial scintigraphy, an
      ischemia group (A; n=49) and a group with stable cardiovascular disease without
      exercise induced ischemia (B; n=87) were distinguished. Risk factors and
      lipoprotein profile of both groups were comparable. Serum levels of serum C
      reactive protein (CRP), IL-6, sTNF-RI, IGF-I, neopterin, serotonin and prolactin
      did not present any significant difference between the two groups. CONCLUSIONS:
      We conclude that measurement of these (inflammatory) parameters does not help to
      delineate post-PCI cardiac patients with and without exercise-induced ischemia.

PMID- 15556776
TI  - Temporal and spatial characterization of cellular constituents during neointimal
      hyperplasia after vascular injury: Potential contribution of bone-marrow-derived
      progenitors to arterial remodeling.
AB  - BACKGROUND: Exuberant smooth muscle cells (SMCs) hyperplasia is the major cause
      of postangioplasty restenosis. We suggested that circulating smooth muscle
      progenitor cells might contribute to lesion formation after vascular injury.
      METHODS: We extensively investigated the cellular constituents during neointimal
      formation after mechanical vascular injury. RESULTS: A large wire was inserted
      into the mouse femoral artery, causing complete endothelial denudation and marked
      enlargement of the lumen with massive apoptosis of medial SMCs. At 2 h, the
      injured artery remained dilated with a thin media containing very few cells. A
      scanning electron microscopy showed fibrin and platelet deposition at the luminal
      side. One week after the injury, CD45-positive hematopoietic cells accumulated at
      the luminal side. Those CD45-positive cells gradually disappeared, whereas
      neointimal hyperplasia was formed with alpha-smooth muscle actin (SMA) positive
      cells. Bone marrow cells and peripheral mononuclear cells differentiated into
      alpha-SMA-positive cells in the presence of PDGF and basic FGF. Moreover, in bone
      marrow chimeric mice, bone-marrow-derived cells substantially contributed to
      neointimal hyperplasia after wire injury. CONCLUSION: These results suggest that
      early accumulation of hematopoietic cells may play a role in the pathogenesis of
      SMC hyperplasia under certain circumstances.

PMID- 15556777
TI  - The ventricular epicardial fat is related to the myocardial mass in normal,
      ischemic and hypertrophic hearts.
AB  - BACKGROUND: The purpose of the present study was to evaluate the extent of the
      ventricular epicardial fat and its relationship with the underlying myocardium,
      neither of which is still completely understood. METHODS: A total of 117 autoptic
      human hearts was subdivided into four groups: normals (N), ischemics (I),
      hypertrophics (H) and hypertrophic-ischemics (HI). In each heart, the ventricular
      myocardial and epicardial fat weights were measured. On the basis of these data,
      the epicardial fat percentage within the ventricles was calculated. RESULTS: The
      left, right and total ventricular fat weights were greater in H and HI than in N
      and I (P<.05, P<.05, P<.01, respectively). No differences were detected in the
      epicardial fat weights in comparing H versus HI and N versus I. Moreover, the fat
      percentage in each ventricle did not vary between the four groups. However, if
      compared with the right ventricle, the left ventricle showed an epicardial fat
      percentage consistently lower (P<.0001). In nonhypertrophied hearts (N and I),
      the body mass index and the total epicardial fat weight were correlated (P<.05),
      whereas in hypertrophied hearts (H and HI), they were not. CONCLUSIONS: A
      constant fat-muscle ratio exists in each ventricle, which is not influenced by
      ischemia or hypertrophy. Accordingly, during the hypertrophic process, the
      ventricular fat and the underlying myocardium show a parallel and correlated
      increase in their masses.

PMID- 15556778
TI  - Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual
      association.
AB  - INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital
      systemic angiodysplasia with multiple vascular malformations in the skin,
      gastrointestinal tract and, less often, in other internal organs and the brain.
      CASE REPORT: A 36-year-old man with past history of BRBNS was admitted to our
      hospital for progressive dyspnea and fatigue. Primary pulmonary hypertension
      (PPH) was diagnosed. He then developed acute abdominal pain and dyspnea, dying in
      a few hours due to sudden cardiac arrest. Postmortem examination demonstrated
      angiomatous lesions located in the skin, small bowel, heart, lungs, liver and
      thyroid. The lesions were slightly raised, soft and compressible and
      microscopically consisted of dilated vascular channels lined by a flattened
      endothelium. The vascular wall was formed by several layers of smooth muscle
      cells, intermixed with abundant aggregates of elastic lamellae and thin collagen
      fibers. Luminal thrombi were a frequent finding. In the small bowel, we
      identified the presence of an abnormally large artery directly opening into a
      thin-walled venous channel. The most striking finding in the lungs was the
      presence of thrombi of varying age in the lumen of segmental and elastic
      arteries, as well as muscular arteries and arterioles. Severe medial hypertrophy
      of muscular arteries and muscolarization of arterioles were also present. Intimal
      proliferative lesions and plexiform lesions were never observed. CONCLUSION: The
      pulmonary findings are consistent with recurrent thromboembolic events from
      shunts in the visceral lesions. To our knowledge, this is the first report of
      BRBNS with visceral arterovenous (AV) fistulae complicated by thromboembolic
      pulmonary hypertension (PH).

PMID- 15556779
TI  - Trypanosoma cruzi myocardial infection reactivation presenting as complete
      atrioventricular block in a Chagas' heart transplant recipient.
AB  - A 56-year-old man underwent orthotopic heart transplantation because of end-stage
      Chagas' cardiomyopathy. One hundred and ten days following heart transplantation,
      an electrocardiogram tracing showed complete atrioventricular block, which was
      treated with temporary transvenous pacemaker insertion. An underlying
      endomyocardial biopsy was graded 3A. The patient was treated with pulse steroid
      therapy. One week later, the patient died of multiorgan failure secondary to
      septicemia. A careful review of the endomyocardial biopsy showed nests of
      parasites in the myocardial tissue accompanied by mononuclear cell infiltrate
      similar to that found in acute graft rejection. Thus, complete atrioventricular
      block may be another clinical manifestation of Trypanosoma cruzi infection
      reactivation in Chagas' heart transplant recipients.

PMID- 15556780
TI  - Late constrictive involvement of the pericardium in a case of previous
      myocarditis.
AB  - Constrictive pericarditis (CP) is a highly relevant disease clinically because
      pericardiectomy represents the only curative therapeutic approach. Previous
      cardiac surgery or mediastinal radiation may cause CP, however, infectious agents
      account for a substantial portion of CP. In this report, we present a patient
      with previous biopsy-proven myocarditis and positive seroconversion against
      coxsackievirus B3 without clinical evidence of acute pericardial involvement who
      developed CP after a prolonged period of time. This suggests that infectious
      particles primarily infecting the myocardium may lead to chronic inflammatory
      responses of the pericardium, thus causing CP even at late clinical stages. This
      case emphasizes the important fact that primary myocarditis may not only cause
      systolic ventricular impairment but may also induce diastolic dysfunction of the
      heart, either as restrictive cardiomyopathy or, as in this case, through
      inflammatory involvement of the pericardium, leading to CP.

PMID- 15556781
TI  - Spontaneous coronary artery dissection mimicking aortic dissection.
AB  - A 51-year-old woman suffered rapidly irreversible cardiogenic shock with left
      hemiparesis. Transesophageal echocardiography, which represents an essential
      imaging tool in the emergency room, ruled out aortic dissection involving branch
      vessels but did not allow an in vivo diagnosis of spontaneous coronary
      dissection. The in vivo diagnosis of spontaneous coronary dissection is rather
      difficult because of the dramatic clinical presentation and selective coronary
      angiography requirement.

PMID- 15556782
TI  - A light-hearted look at a lion-hearted organ (or, a perspective from three
      standard deviations beyond the norm) part 2 (of 2 parts).
AB  - Throughout history, the heart has been associated not only with its life
      sustaining function but also with its close ties to the human emotions. In this
      literature and internet review, we attempt to gather and organize information
      from both of these perspectives as they relate to the heart in the following 11
      categories: (1) fun facts, (2) medical photography, (3) history, (4) languages
      (etymology), (5) nonmedical English expressions, (6) death, (7) the arts, (8)
      movie titles, (9) song titles, (10) Shakespeare, and (11) the Bible. Part 1
      (previously published) covered the first five topics, and Part 2 will cover the
      last six topics. These data may be useful to those who are engaged in teaching
      about the cardiovascular system.

PMID- 15556783
TI  - Asymptomatic right atrial cavernous hemangioma: a case report and review of the
      literature.
AB  - A case of asymptomatic right atrial cavernous hemangioma in a 50-year-old man is
      reported. With right atriotomy under total cardiopulmonary bypass, the right
      atrial mass was identified as arising from the noncoronary Sinus of Valsalva. The
      mass was successfully resected with the Sinus of Valsalva closed primarily. The
      patient is alive and well 9 months following the operation. The incidental
      discovery of the mass, clinical evaluation, operative procedure, and pathologic
      findings are reported. We also briefly discuss the epidemiology, natural history,
      and the diagnostic and therapeutic approaches to cardiac tumors.

PMID- 15556784
TI  - DeBakey Surgitool mechanical heart valve prosthesis, explanted at 32 years.
AB  - Contemporary mechanical heart value prostheses are expected to last "just about
      forever" or the patient's lifeline. They do however still suffer complications,
      some of which necessitate premature explantation. Complications today are mainly
      related to patient compliance with anticoagulant medication, infection and
      hemorrhage. The DeBakey Surgitool mechanical heart valve was the first such
      device to have Pyrolyte components. We present a DeBakey surgitool mechanical
      heart valve that was in place for 32 years! It was explanted for dysfunction
      related to tissue overgrowth and not to its related components. With good patient
      compliance, this mechanical heart valve prosthesis is an example of good
      prosthetic valve durability.

PMID- 15556797
TI  - Divided we stand.

PMID- 15556798
TI  - Poliomyelitis: very small risks and very large risks.

PMID- 15556799
TI  - Intravenous immunoglobulins for Alzheimer's disease.

PMID- 15556800
TI  - Gross underfunding of stroke research.

PMID- 15556801
TI  - Autism: the search for the missing link.

PMID- 15556802
TI  - Steroids CRASH out of head-injury treatment.

PMID- 15556803
TI  - Environmental risk factors in multiple sclerosis aetiology.
AB  - The epidemiology of multiple sclerosis (MS) has been intensively studied. It is
      conceptualised as a complex disease in which genetic and environmental factors
      act together to cause disease. There are temporal and geographic variations in
      disease risk, and risk of disease may be affected by migration between regions of
      differing risk. Numerous potential causal factors including infection,
      immunisations, physical and emotional stressors, climate, diet, and occupational
      exposures have been studied using various observational study designs. Thus far,
      no single environmental exposure has been consistently identified as a causal
      factor in MS, but sufficient data have accumulated that causal pathways should be
      postulated and tested. This review will focus on the environmental epidemiology
      of MS.

PMID- 15556804
TI  - Surgical treatment for Parkinson's disease.
AB  - Since the early 1930s, physicians have developed and refined various surgical
      therapies for the treatment of Parkinson's disease. In this review we examine
      some of the problems associated with early surgical therapies, the development of
      new techniques and targets, and the results of clinical trials examining the
      safety and efficacy of these techniques. Ablative techniques include pallidotomy,
      thalamotomy, and, more recently, subthalamotomy. Because of concern over the high
      incidence of side-effects associated with bilateral ablative procedures,
      alternative approaches were explored. Deep brain stimulation (DBS) was
      subsequently developed and successfully applied in the internal globus pallidus,
      subthalamic nucleus, and thalamus for the treatment of Parkinson's disease.
      Recent approaches include biological neurorestorative techniques--surgical
      therapies with transplantation, gene therapy, and growth factors are all being
      studied. Although a great deal of work remains to be done, advances in surgical
      therapies for the treatment of Parkinson's disease are moving forward at an
      unprecedented pace.

PMID- 15556805
TI  - Current drug treatment of epilepsy in adults.
AB  - The choice of antiepileptic drugs (AEDs) is rapidly increasing. This review looks
      at the evidence that guides the decision of which AED to start as monotherapy and
      aims to aid the choice of treatment if monotherapy fails. Unfortunately, the
      evidence supporting the prescribing of new drugs is sparse, because most
      randomised controlled trials answer questions focused on regulatory requirements
      rather than on clinical use. Ultimately, the choice of one AED will be determined
      by an individual risk-benefit assessment in which the most effective drug for an
      individual patient is chosen, and one that would have the lowest risk of
      significant harm. It is the risk of chronic toxic effects and issues of
      teratogenicity for women that may affect the choice of drug therapy to the
      greatest degree. In the future there is a need to improve the quality of clinical
      data on efficacy and harmful effects of AEDs.

PMID- 15556806
TI  - Corticobasal degeneration.
AB  - Corticobasal degeneration is a progressive neurodegenerative disease that
      typically presents with asymmetrical parkinsonism and cognitive dysfunction.
      Recent molecular advances have given some clues to the pathogenesis of the
      disease. Clinical diagnosis is complicated by both the variability of
      presentation of true corticobasal degeneration, for example as a dementing
      illness, and the syndromes that look like it but are caused by other
      neurodegenerative diseases. Although definitive diagnosis of corticobasal
      degeneration can only be made at post-mortem examination, recent advances in
      imaging can assist the clinician with diagnosis. Treatment options remain limited
      and mostly address symptoms.

PMID- 15556807
TI  - The promise of minocycline in neurology.
AB  - The capacity of minocycline to alleviate disease for several neurological
      disorders in animals is increasingly being recognised. Indeed, that one drug
      alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal
      cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral
      sclerosis is astounding. In this review, we describe the evidence for the
      efficacy of minocycline in several animal models of neurological disease, discuss
      the mechanisms by which minocycline affects a range of neurological diseases with
      diverse causes, and introduce the emerging investigation of minocycline in
      clinical neurology. The encouraging results of minocycline in experimental
      neurology bode well for its therapeutic use in human neurological diseases.

PMID- 15556808
TI  - Enzyme-replacement therapy for metabolic storage disorders.
AB  - BACKGROUND: After many years of intensive investigation, enzyme-replacement
      therapy (ERT) has become standard treatment for patients with type 1 (non
      neuronopathic) Gaucher's disease. ERT has greatly changed the clinical course of
      this disorder by reducing hepatosplenomegaly, by improving anaemia and
      thrombocytopenia, and by ameliorating skeletal damage. This example has prompted
      the investigation of ERT for several other metabolic disorders. The results of
      several of these trials have recently been published. RECENT DEVELOPMENTS: In
      addition to Gaucher's disease, the effects of ERT in four other major metabolic
      storage disorders have been reported. Among these rare orphan diseases are
      Fabry's disease, in which the heart, kidney, gastrointestinal tract, and
      peripheral nerves are damaged; Pompe's disease, in which the heart, skeletal
      muscles, and brain are involved; Hurler's disease and Maroteaux-Lamy syndrome in
      which the eyes, liver, joints, and skeleton are usually affected. Responses to
      ERT in these four disorders have generally been encouraging although the degree
      and extent of benefit vary considerably. WHERE NEXT: There are several critical
      features of ERT that require attention and amelioration. Among these are the
      development of severity-score indices that can be used to explicitly quantify the
      benefit of ERT. The benefit of this treatment has been slight in Fabry's disease
      and is yet to be fully shown in the other three disorders. Secondly, novel
      technologies need to be developed to deliver therapeutic enzymes effectively to
      tissues such as the cardiac muscle and kidney in Fabry's disease, skeletal muscle
      in patients with Pompe's disease, and to joint tissues and structures in patients
      with Hurler's disease and Maroteaux-Lamy syndrome. Finally, an all-encompassing
      concern is to devise methods to ameliorate the damage to the central and
      peripheral nervous systems that occurs in specific phenotypes of these disorders.
      In this review we descibe emerging strategies that seem to be useful in these
      critical regards.

PMID- 15556809
TI  - Ch...Ch...Changes.

PMID- 15556810
TI  - New frontiers in echocardiography: hand-carried ultrasound devices.

PMID- 15556811
TI  - New frontiers in echocardiography: hand-carried ultrasound devices. The
      cardiologist's view.

PMID- 15556812
TI  - New frontiers in echocardiography: hand-carried ultrasound devices. The
      intensivist's view.

PMID- 15556813
TI  - New frontiers in echocardiography: hand-carried ultrasound devices. The
      anesthesiologist's view.

PMID- 15556814
TI  - Calculation of left ventricular flow velocity propagation from M-mode
      echocardiography.

PMID- 15556816
TI  - Negative predictive value of multiplane transesophageal echocardiography in the
      diagnosis of infective endocarditis.
AB  - BACKGROUND: The clinical implications of a negative multiplane transesophageal
      echocardiography (TEE) have not yet been reported. We aim to determine the
      negative predictive value (NPV) of a negative multiplane TEE in patients with
      suspected infective endocarditis (IE). METHODS AND RESULTS: We identified 83
      consecutive patients with suspected IE and negative multiplane TEE from our
      echocardiographic database. Of 74 patients with a minimum of 1-month follow-up,
      only 1 patient developed "definite IE". Eight patients had "possible IE". The
      calculated NPV of multiplane TEE in IE was 98.6% if we only considered the case
      of "definite IE". If we assumed that all patients with "possible IE" had the
      disease, then the NPV of multiplane TEE was 87.8%. CONCLUSIONS: Multiplane TEE is
      a highly accurate diagnostic tool with excellent NPV in IE. However, in a highly
      suspicious clinical setting for IE, a repeat TEE is still recommended to assess
      evolving echocardiographic features.

PMID- 15556815
TI  - Mitral annular motion as a surrogate for left ventricular ejection fraction: real
      time three-dimensional echocardiography and magnetic resonance imaging studies.
AB  - AIMS: To validate the accuracy of mitral annular motion assessed by real-time
      three-dimensional echocardiography (RT3DE) as a surrogate for determination of
      the left ventricular function in comparison with magnetic resonance imaging
      (MRI). METHODS AND RESULTS: Forty-seven patients with a variety of cardiac
      pathologies underwent both RT3DE and MRI exams. After 3D data sets were
      transferred to a PC with a custom-made program, nine consecutive rotational
      apical plane images (20 degrees apart) were displayed. The two mitral leaflet
      insertion points were manually identified in each plane. The geometry of the
      mitral annulus was reconstructed from a total of 18 coordinates (x, y, z), and
      the changes in mitral annular area and mitral annular motion along the apical
      long axis were calculated. The left ventricular ejection fraction (LVEF)
      determined by MRI was 41+/-18%, and 24 patients had LVEF<50%. Mitral annular
      motion (y) obtained by RT3DE was 11+/-5 mm and correlated moderately well with
      LVEF (x) measured by MRI (r=0.84, y=0.25x+0.43, p<0.0001). The mitral annular
      motion<12 mm was a good threshold for detecting LVEF<50% with 96% sensitivity,
      85% specificity, and 91% accuracy. CONCLUSION: Mitral annular motion determined
      by RT3DE correlated moderately well with LVEF; and systolic motion, <12 mm,
      accurately detected LV dysfunction.

PMID- 15556817
TI  - Localization and quantification of mitral valve prolapse using three-dimensional
      echocardiography.
AB  - AIMS: Mitral valve prolapse is a common source of severe mitral regurgitation in
      Western countries. Three-dimensional echocardiography can provide views of the
      entire valve, allowing a complete assessment of the valve leaflets and
      commissures. It has the potential to precisely locate and quantify mitral valve
      prolapse. METHODS AND RESULTS: Between January 1997 and December 2000, 91
      patients with severe mitral regurgitation due to mitral valve prolapse underwent
      a transesophageal echocardiography with three-dimensional reconstruction of the
      mitral valve as part of their pre-operative work-up. The location and extent of
      the prolapse by echo was compared to the surgical status. The volume of
      prolapsing leaflet was calculated and compared to the volume of resected tissue
      whenever a repair was attempted. There was an excellent correspondence between
      the echographic localization of the prolapse and surgical inspection, and between
      the volume of prolapsing and surgically resected tissue (r=0.94, p<0.0001).
      CONCLUSIONS: In patients with severe mitral regurgitation due to mitral valve
      prolapse, 3D echo allowed a precise localization and an accurate quantification
      of the prolapsing portion of the leaflets. This technique can provide refinements
      in the surgical planning of mitral valve repair and in the selection of
      candidates for this intervention.

PMID- 15556818
TI  - Echocardiographic evaluation of patients receiving a new left ventricular assist
      device: the Impella recover 100.
AB  - The aim of this study was to suggest a protocol for serial echocardiographic
      evaluations in patients undergoing circulatory support by a new miniaturized
      electric axial pump, the Impella recover 100 (IR 100). IR 100 is implanted
      through the ascending aorta into the left ventricle drawing blood from the left
      ventricle to the aorta. METHODS AND RESULTS: This protocol has been applied in
      eight patients receiving twelve IR 100 implants. Before implantation
      echocardiography was useful to rule out anatomic contraindications. During and
      after implantation echocardiography provided informations for correct positioning
      and evaluation of left ventricular filling necessary to optimize pump
      performance. During assistance it gave important informations to assess left and
      right ventricular function. CONCLUSION: Echocardiography has pivotal role in IR
      100 management before, during and after implantation.

PMID- 15556819
TI  - Regional myocardial function in an arrhythmogenic milieu: tissue velocity and
      strain rate imaging in a patient who had hypertrophic cardiomyopathy with
      recurrent ventricular tachycardia.
AB  - We report the use of tissue velocity and strain rate imaging for detecting marked
      segmental variations and asynchrony in left ventricular systolic and diastolic
      functions of a 40-year-old patient with hypertrophic obstructive cardiomyopathy
      who died of an intractable ventricular tachycardia. These newer techniques have
      advantages for identifying heterogeneity in regional myocardial function in
      hypertrophic cardiomyopathy.

PMID- 15556820
TI  - Quantitative analysis of intraprocedural myocardial contrast echocardiography
      during percutaneous septal ablation for hypertrophic obstructive cardiomyopathy.
AB  - AIMS: We tested whether procedural success of percutaneous septal ablation for
      hypertrophic obstructive cardiomyopathy is related to quantitative measurements
      of intraprocedural myocardial contrast echocardiography. METHODS AND RESULTS: In
      a study group of 34 patients, the mean area of the contrast depot was 8.5+/-2.5
      cm2, its length along the left ventricular endocardial border 3.0+/-0.7 cm and
      its proximal edge 2.0+/-0.6 cm upstream the point of mitral-septal contact.
      Clinical and hemodynamic success was achieved in all but one patient 3 months
      following percutaneous septal ablation. The proximal edge of the ablation lesion
      correlated weakly (r=0.5) with the proximal edge of the contrast depot with
      respect to their distance from the mitral valve leaflet tips. No other
      correlations were found between the efficacy of percutaneous septal ablation and
      various quantitative measurements of intraprocedural contrast echocardiography.
      CONCLUSIONS: The localization of the ablation lesion 3 months after percutaneous
      septal ablation is predicted by the localization of the contrast depot with
      respect to the point of mitral-septal contact. The final hemodynamic effect of
      the ablation lesion, however, does not correlate with quantitative parameters of
      intraprocedural contrast echocardiography, but appears to be the result of an
      individual remodeling process.

PMID- 15556821
TI  - Second harmonic transthoracic echocardiography: the new reference screening
      method for the detection of patent foramen ovale.
AB  - AIM: Transesophageal echocardiography (TEE) is still considered as the reference
      method for the non-invasive detection of right-to-left shunts. Echocardiographic
      laboratories are spending most of their time performing TEE studies to exclude a
      thromboembolic cardiac disease. In a considerable proportion of these patients
      the question can be simplified to exclude a PFO. Replacing these TEE studies by
      TTE would result in a considerable gain in time and money. We evaluated the value
      of transthoracic echocardiography with second harmonic imaging (TTE) (SH) and
      peripheral intravenous agitated saline solutions in the detection of patent
      foramen ovale (PFO) in a large cohort of patients. METHODS: In 256 consecutive
      patients, TEE and TTE (SH) with the consecutive administration of three
      intravenous contrast injections of agitated saline injections before the release
      phase of the Valsalva manoeuvre were performed. Semi-quantification and timing of
      contrast passage were assessed during both imaging modalities. A shunt was
      present if at least one imaging modality showed microbubbles appearing in the
      left atrium. PFO was defined when these bubbles appeared early and arteriovenous
      pulmonary malformations were suspected if bubbles appeared late after the
      opacification of the right atrium. Shunts were considered important when >20
      bubbles were present in one frame in the left atrium or left ventricle. RESULTS:
      From the 256 patients, 60 presented a passage of contrast from the right to the
      left atrium in at least one imaging modality. PFO was detected by TEE in 53
      patients and by TTE in 55 patients (sensitivity: 90.5% and specificity: 96.5% if
      TEE is accepted as the golden standard) (p>0.05). Considering only the important
      shunts TEE detected 39 important shunts and TTE 46 important shunts (sensitivity:
      89.7% and specificity: 94.6%) (p>0.05). AV pulmonary malformations were detected
      by TEE in 7 patients and by TTE in 10 patients (sensitivity: 85.7% and
      specificity: 98.3%) (p>0.05). CONCLUSIONS: In this large cohort of patients TTE
      (SH) is as accurate as TEE for the detection of PFO and late right-to-left
      shunts. If the only purpose of TEE is the detection of PFO such as in young
      cryptogenic stroke patients and in divers, TEE can be replaced by TTE (SH).

PMID- 15556822
TI  - The impact of transesophageal echocardiography on daily clinical practice.
AB  - The development of transesophageal echocardiography (TEE) almost 20 years ago has
      tremendously widened the diagnostic potential of cardiac ultrasound and has,
      without doubt, strongly improved our pathophysiological understanding of many
      cardiovascular diseases such as aortic dissection, mitral valve disease or
      ischemic stroke. Especially the introduction of multiplane transducers that allow
      imaging of the cardiac structures from various scan plane orientations has
      yielded a level of diagnostic accuracy that is seldom attained by other imaging
      modalities. The outstanding image quality as well as the high temporal and
      spatial resolution provided by TEE renders the method especially suited to
      visualize small and rapidly moving structures, such as left atrial thrombus
      formation and valvular vegetations. In addition, TEE is exceptional in its
      capability to scan the heart from perspectives that cannot be easily attained by
      any other modality, thus enhancing its diagnostic yield. In the last few years
      the clinical application of TEE has been extended from a pure diagnostic tool to
      an indispensable monitoring adjunct for percutaneous interventional procedures as
      well as for the intra- and peri-operative monitoring in the operating theatre and
      on the intensive care unit. In the surroundings of emerging sophisticated
      technologies to image the heart and the great vessels within the thorax such as
      multi-slice computed tomography and cardiovascular magnetic resonance imaging TEE
      asserts a firm place in the diagnostic armamentarium for the cardiologist. This
      review will focus the impact of TEE in daily clinical practice and on possible
      future applications of the technique.

PMID- 15556823
TI  - Acute myocardial infarction after a negative dobutamine stress echocardiogram.
AB  - Acute myocardial infarction is a rare complication of dobutamine stress
      echocardiography (DSE). We described angiographic findings of a patient who
      developed acute inferior ST segment elevation myocardial infarction 2h after a
      normal dobutamine stress echocardiogram. The patient failed thrombolysis and
      underwent coronary angiography, which showed 60% stenosis of proximal right
      coronary artery with a complex ulcerated lesion and intracoronary thrombus. These
      findings suggest that myocardial infarction following DSE does not necessarily
      occur in patients with severe obstructive coronary artery disease. High shear
      stress may result in destabilization of a complex plaque with subsequent
      thrombotic occlusion, despite the absence of a flow-limiting lesion at the time
      of DSE.

PMID- 15556824
TI  - High-dose adenosine infusion provokes oscillations of chest pain without
      correlation to opioid modulation: a double-blind controlled study.
AB  - Adenosine is a neuromodulator with both excitatory and inhibitory effects in
      different organs. High-dose adenosine infusion provokes chest pain in patients
      and healthy volunteers. This study examines the nature of chest pain and whether
      it is modified by the mu opioid receptor agonist (beta-endorphin) or a
      nonselective opioid antagonist (naloxone). Ten healthy volunteers with a mean age
      of 26 +/- 3 years participated in the study. The study was performed during 3
      sessions. During every session the subjects were given a high dose of adenosine
      infusion (140 microg/kg/min) for 22 minutes. After 5 minutes, the subjects were
      randomized in a double-blind order on 1 of the 3 categories: (1) as placebo, NaCl
      bolus for 2 minutes followed by NaCl infusion for 15 minutes; (2) beta-endorphin
      bolus followed by infusion; and (3) naloxone bolus followed by NaCl infusion.
      Hemodynamic and pain parameters were monitored. During adenosine infusion, all
      volunteers experienced chest pain with oscillations of pain intensity. The
      oscillations continued during beta-endorphin and naloxone. There were no
      significant differences between hemodynamic and pain parameters during beta
      endorphin or naloxone compared to adenosine infusion. High-dose infusion of
      adenosine provokes chest pain with oscillations of algesia and pain-free
      intervals. Peripheral opioid administration did not influence the adenosine
      provoked chest pain. PERSPECTIVE: Adenosine-induced oscillations of pain and pain
      free intervals could theoretically be a sign of neuronal reflex activity
      dependent on spatiotemporal summation of adenosine excitatory and inhibitory
      properties. This could contribute to the complex nature of angina pectoris.
      Peripheral opioid receptors might not be involved in the oscillations.

PMID- 15556825
TI  - Usefulness of pain drawings in identifying real or imagined pain: accuracy of
      pain professionals, nonprofessionals, and a decision model.
AB  - The aim of this study was to determine the accuracy of pain specialists,
      nonprofessionals, and a decision model in judging whether a pain diagram was
      marked by a patient with chronic pain or by a healthy volunteer. Two hundred
      twenty-eight pain drawings were shown in random order to 10 pain medicine
      physicians, 10 pain medicine fellows, 10 nonphysician specialists, and 10
      nonprofessionals. One half of the drawings (n = 114) had been produced by
      patients treated at a pain center and the other half (n = 114) by healthy
      individuals who were instructed to mark the diagrams as if they had a pain
      problem. The nonprofessionals were found to be 51.5% accurate, pain medicine
      fellows 52.7%, nonphysician specialists 54.3%, and pain medicine physicians 55.2
      % accurate at distinguishing drawings by actual pain patients from drawings from
      volunteers without pain. A decision model was able to achieve 68.9% accuracy in
      determining which drawings were made by pain patients and which drawings were
      made by healthy individuals. The results suggest that subjective assessment of
      pain drawings alone is not useful in determining whether someone has real or
      imagined pain. A decision model that makes decisions on the basis of the number
      of highlighted squares on the pain diagram can identify real pain drawings with
      greater accuracy than humans. PERSPECTIVE: Pain drawings are clinically useful
      but have limitations. This study illustrates some of the benefits of computerized
      pain assessment and highlights the importance of not judging patients on the
      basis of one source of information.

PMID- 15556826
TI  - Prevalence of fear of pain and activity in patients with fibromyalgia syndrome.
AB  - Patients with fibromyalgia syndrome (FMS) report pain, fatigue, emotional
      distress, activity avoidance, and disability. The role of fear of pain and
      activity in FMS patients has received only limited attention. FMS patients (N =
      233) underwent examinations by a physician, physical therapist, and psychologist
      and completed measures of fear of pain and activity, disability, depressive mood,
      impact, and pain. Patients with high levels of fear of pain and activity (38.6%)
      reported greater disability (t = 4.02, P < .001), depressed mood (t = -4.14, P <
      .001), pain severity (t = -2.71, P < .01), and lower treadmill performance (t = 
      2.39, P < .05) than patients with low fear. Patients classified on the
      Multidimensional Pain Inventory as Dysfunctional reported greater fear than
      Interpersonally Distressed patients and Adaptive Copers (F = 8.13, P < .001).
      Only 50% of Dysfunctional patients, however, met the criterion of high fear,
      whereas 23.4% of Adaptive Copers met this criterion. Demographic factors,
      perceived disability, and Multidimensional Pain Inventory subgroup significantly
      predicted fear of pain and activity, accounting for 21.2% of the variance. Fear
      of pain and activity is prevalent among FMS patients. Treatment should address
      patient fears, because it might reduce disability and rates of nonadherence and
      attrition from outcome studies. PERSPECTIVE: Fear of movement is a significant
      concern for chronic pain sufferers because these behaviors maintain pain and
      increase disability. This study examined the role of fear in FMS, including
      associations between fear of pain/movement, pain severity, depressed mood,
      physical performance, and disability in FMS subgroups.

PMID- 15556827
TI  - Neuropathic pain symptoms relative to overall pain rating.
AB  - The influence of sensory symptoms on overall simple pain ratings in neuropathic
      pain is not well understood. The goal of this study was to determine this
      relationship by using the Neuropathic Pain Questionnaire (NPQ) and Neuropathic
      Pain Scale (NPS) in patients who had neuropathic pain. Overall pain intensity
      ratings were assessed by means of Average and Worst Pain ratings from the Brief
      Pain Inventory. Ongoing average pain was rated as 5.7 and worst pain as 7.7 on 0
      to 10 scale, and it was present in 96% of patients, whereas symptoms that are
      commonly studied in the laboratory, such as increased pain due to touch and due
      to heat, were much less frequent (64% and 38%, respectively). Worst pain was most
      highly correlated with shooting, stabbing, and distress symptom complex, which
      was in contrast to Average pain, which was most highly correlated with symptom
      complex consisting of a large number of items. Analysis of conceptually related
      thermal heat sensation types of pain, spontaneous "burning" pain and the evoked
      pain "increased due to heat," showed that spontaneous burning pain was reported
      at much higher frequency and intensity than the evoked increased pain due to
      heat. There was no statistically significant difference between descriptors from
      NPS and NPQ among subgroups of neuropathic pain, such as polyneuropathy,
      radiculopathy, or posttraumatic neuralgia, but this could be in part due to
      relatively small number of patients in these subgroups of neuropathic pain.
      Quantitative analysis, as performed in this study, is one of the steps in
      developing an approach for elucidating the relationship between neuropathic pain
      symptoms and underlying mechanisms. PERSPECTIVE: Assessment of neuropathic pain
      symptoms by means of specifically designed questionnaires provides significant
      insight into patients' pain experience, including pain overall, which is under
      many influences. Further research of this type can contribute to advances in
      mechanism-based diagnosis and treatment.

PMID- 15556828
TI  - How do people ease their pain? A population-based study.
AB  - We investigated how a general population treat their pain and determined factors
      affecting use of different pain management strategies. From the respondents of a
      cross-sectional postal survey we selected those who had experienced pain during
      the past 7 days (n = 3641) and analyzed how they had tried to manage their pain
      during the past 6 months. The most common pain management strategies were use of
      over-the-counter medicines (53% of 3641 respondents), physical exercise (52%),
      prescription medicines (35%), and visiting a physician (33%). The location of
      pain was related to which pain management strategy was chosen. Use of multiple
      (>4) treatments was related to prolonged pain, having several (>3) painful
      locations, high intensity and frequency of pain. PERSPECTIVE: This study
      indicates that people with pain are active in trying different treatments. Self
      care strategies, especially over-the-counter medicines and physical exercise, are
      common ways to manage pain at the population level.

PMID- 15556829
TI  - Evaluation of pain in patients with oral squamous cell carcinoma.
AB  - In this study we have developed and tested a novel pain questionnaire to measure
      the pain experienced by patients with oral squamous cell carcinoma. The
      questionnaire consisted of 8 questions rated by the patient on a visual analog
      scale. Patients completed the questionnaire at the time of initial presentation
      before surgical treatment. None of the patients were taking analgesics. The
      responses were then scored and compiled with patient data and pathology reports.
      Of the 15 completed questionnaires, 14 patients reported some level of functional
      restriction from pain (mean, 46.6 +/- 25.2, scale of 0 to 100 mm). On average,
      patients experienced significantly higher function-related, rather than
      spontaneous, pain intensity and sharpness. Men (n = 8) had a significantly higher
      level of function-related pain intensity and sharpness than women had (n = 7).
      There was a strong correlation between nodal disease and increased levels of
      spontaneous intensity, sharpness, throbbing, and overall functional restriction.
      PERSPECTIVE: The results of this study indicate the heterogeneous nature and
      function dependence of oral cancer pain. The questionnaire we have developed in
      this study will allow for correlations between pain parameters and specific tumor
      biology in future studies.

PMID- 15556830
TI  - Pain management in osteoarthritis: a focus on onset of efficacy--a comparison of
      rofecoxib, celecoxib, acetaminophen, and nabumetone across four clinical trials.
AB  - We compared onset of efficacy (during days 1 to 6) of 2 coxibs (rofecoxib,
      celecoxib) with acetaminophen and nabumetone by using a prespecified approach to
      data from 4 similarly designed 6-week randomized osteoarthritis trials. In 2
      trials, rofecoxib (12.5 mg and 25 mg once daily) was compared with celecoxib (200
      mg once daily) and acetaminophen (4000 mg daily). In the other 2 trials,
      rofecoxib (12.5 mg) was compared with nabumetone (1000 mg once daily) and
      placebo. Efficacy end points included Patient Global Response to Therapy and
      Western Ontario and McMaster Osteoarthritis Index scores. Rofecoxib (12.5- and 25
      mg doses) consistently demonstrated a faster onset of osteoarthritis (OA)
      efficacy than the comparator drugs during the first 6 days of therapy of OA
      patients experiencing "flare." Acetaminophen resulted in the slowest onset of
      efficacy. There was a strong correlation (0.7) between efficacy response during
      days 1 to 6 and that averaged over 6 weeks. Rates of discontinuation as a result
      of lack of efficacy were significantly lower (P < .02) for each of the coxib
      treated groups compared with acetaminophen and for rofecoxib 12.5 mg (P = .01)
      compared with nabumetone. Rofecoxib treatment, with its faster onset of OA
      efficacy and lower rates of related discontinuations, might provide efficacy
      advantages in the treatment of OA pain. PERSPECTIVE: The efficacy of rofecoxib,
      celecoxib, nabumetone, and acetaminophen is established for the majority of OA
      patients within the first 6 days of therapy, and this predicts efficacy during
      the longer term. Rofecoxib provides significantly faster time to onset of
      efficacy and better improvement on multiple measures versus the comparators.

PMID- 15556831
TI  - Self-care behaviors for muscle pain.
AB  - This investigation examined self-care behaviors for muscle pain because of the
      prevalence of musculoskeletal pain and the substitution of self-care for formal
      medical care. In Study 1, university students (N = 187) completed a retrospective
      questionnaire about self-care for muscle pain. In Study 2, muscle pain was
      experimentally induced in university students (N = 79) with subsequent
      measurement of self-care. In both studies, stretching and massaging were the most
      frequently performed behaviors, and consuming medication was the least frequently
      performed. In Study 1, the perceived effectiveness of behaviors and level of pain
      required to perform self-care accounted for 12% to 32% of the variance in
      behavior frequency. In Study 2, pain ratings and pain during activities were
      higher among those who performed self-care (ds = .59 to 1.00). These studies
      indicated that self-care behaviors are performed for both naturally occurring and
      experimentally induced muscle pain. However, both studies determined that the
      performance of self-care behaviors did not always correspond with current
      evidence of treatment effectiveness for muscle injuries. Unique opportunities for
      future investigations of self-care behavior models and interventions are
      permitted by muscle pain induction. PERSPECTIVE: Self-care for pain reduction is
      an understudied behavior. This report describes 2 studies of self-care behaviors
      for naturally occurring and experimentally induced muscle pain. The most frequent
      types of self-care behaviors are similar for the types of pain, and the perceived
      effectiveness of behaviors and pain level influence performance of the behaviors.

PMID- 15556832
TI  - Assessment of O-methylated catecholamine levels in plasma and urine for diagnosis
      of autonomic disorders.
AB  - The term 'metanephrines' is used to indicate the two catechol 3-O-methylated
      metabolites of epinephrine (E) and norepinephrine (NE): metanephrine and
      normetanephrine (NMN). The corresponding 3-O-methylated metabolite of dopamine is
      usually referred to as 3-methoxytyramine rather than 3-methoxydopamine and is not
      generally considered a "metanephrine". O-Methylation occurs outside the
      sympathetic neuron and neuroeffector junction. Metanephrines are products of the
      enzyme catechol-O-methyltransferase (COMT). Subsequent conjugation with sulfate
      or deamination by monoamine oxidase (MAO) followed by reduction to vanilmandelic
      acid (VMA) facilitates urinary excretion. For the clinician, measurement of
      normetanephrine provides an index of norepinephrine released during sympathetic
      nervous system activity, whereas metanephrine concentration provides an
      indication of adrenal medullary metabolism of epinephrine prior to its discharge
      into the circulation. Plasma epinephrine concentration is the preferable index of
      adrenal medullary epinephrine discharge. Pheochromocytomas, with their protean
      clinical manifestations, may be diagnostic challenges, but assay of
      metanephrines, especially plasma metanephrine, can be particularly helpful in
      diagnosis. These COMT metabolites may also help in elucidation of still
      undiscovered genetic and acquired disorders of catecholamine metabolism.

PMID- 15556833
TI  - Combined determination with functional and morphological studies of origin of
      nerve fibers expressing transient receptor potential vanilloid 1 in the myenteric
      plexus of the rat jejunum.
AB  - The aim of this study was to determine the action of capsaicin in isolated rat
      intestine and the origin of nerve fibers expressing transient receptor potential
      vanilloid 1 (TRPV1: capsaicin receptor) in the rat jejunum by combination of
      functional and immunohistochemical experiments. Capsaicin (1 microM) produced a
      prolonged relaxation response (52. +/-15.3% of the relaxation response to
      papaverine, mean +/- S.D., n=27) of the isolated jejunum in the presence of
      atropine and guanethidine. Pretreatment with the TRPV1 antagonist, capsazepine
      (10 microM) and ruthenium red (3 microM) significantly reduced the relaxation
      response to capsaicin by 78% (P<0.01) and 38% (P<0.05), respectively.
      Tetrodotoxin and calcitonin gene-related peptide (CGRP)-desensitization
      significantly reduced the response to capsaicin by 72% (P<0.01) and 42% (P<0.01),
      respectively. Therefore, we investigated the distribution of TRPV1
      immunoreactivity (IR) in the myenteric plexus of the rat jejunum. Using antisera
      raised against either the N-terminal or C-terminal domains of rat TRPV1, TRPV1-IR
      was present in the nerve fibers, but not in the cell bodies of myenteric neurons.
      These TRPV1-immunoreactive nerve fibers were running in myenteric ganglia and
      their interconnecting strands. Most TRPV1-immunoreactive nerve fibers showed CGRP
      IR, whereas few VR1-immunoreactive nerve fibers showed substance P-IR. After
      chronic denervation of the extrinsic nerve supply to the jejunum, both the
      relaxation response to capsaicin and TRPV1-immunoreactive nerve fibers completely
      disappeared. These findings indicate that these TRPV1-immunoreactive nerve fibers
      in the rat jejunum derive from extrinsic neurons and that activation of TRPV1
      produces the relaxation response in the rat jejunum, at least in part, through
      the release of CGRP from nerve fibers expressing TRPV1.

PMID- 15556834
TI  - Cardiovascular responses to the injection of L-glutamate in the lateral
      hypothalamus of unanesthetized or anesthetized rats.
AB  - The present experiment was designed to compare the cardiovascular effects of
      injections of 0.1 M L-glutamate (50, 100 or 500 nL) into the anterior (LHa),
      tuberal (LHt) or posterior (LHp) regions of the lateral hypothalamus (LH) of
      either unanesthetized or anesthetized male Wistar rats. In unanesthetized rats, L
      glutamate caused significant depressor responses without significant heart rate
      (HR) effects. L-Glutamate caused similar depressor responses when injected into
      the different LH subregions. A positive trend was observed between depressor
      response intensity and injected volume. In urethane-anesthetized rats, L
      glutamate caused either depressor responses or biphasic responses, characterized
      by a significant initial depressor component followed by a secondary pressor
      response which was significant only after the injection of L-glutamate in 500 nL.
      The depressor component was accompanied by significant bradycardia only when the
      LHa or LHt were stimulated. Similar depressor responses were observed after L
      glutamate microinjection into the different LH subregions. A positive trend was
      observed between depressor response intensity and injected volume. The present
      results suggest that: 1) lateral hypothalamic L-glutamate-sensitive neurons are
      involved in cardiovascular control and may have a wide and homogeneous
      distribution throughout the LH; 2) these neurons are mainly associated to the
      expression of hypotensive responses in unanesthetized rats; and 3) bradycardiac
      responses are evidenced when L-glutamate is microinjected into the LHa and the
      LHt in urethane-anesthetized rats.

PMID- 15556835
TI  - Impaired cardiovascular autonomic control in newly and long-term-treated patients
      with Parkinson's disease: involvement of L-dopa therapy.
AB  - In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent,
      causing orthostatic hypotension. The respective roles of disease progression and
      dopaminergic treatment remain unclear. In this study, we investigated the
      autonomic control of cardiovascular functions and its relation to L-dopa therapy
      in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects
      were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18
      LT patients who had been receiving L-dopa treatment for a long period. ND
      patients were investigated before L-dopa treatment and after stabilization of
      their L-dopa dosage. LT patients were investigated once with their regular
      treatment and once after a 12-h interruption of L-dopa treatment; (3) nine
      healthy subjects served as controls. At each test session, blood pressure (BP),
      heart rate (HR), plasma catecholamines, heart rate variability (HRV), and
      spontaneous baroreflex sensitivity were assessed in the supine and upright
      positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios
      (HR response/deep breathing) and lowered HRV when compared to controls; this was
      evidence of early effects of the disease on autonomic HR control. Introduction of
      L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and
      noradrenaline. Similar changes were found in LT patients when contrasting the
      short-term treatment interruption and the usual L-dopa dosage. The treatment
      linked increase in plasma dopamine also correlated with the decrease in
      noradrenaline. These results showed that mild impairment of autonomic
      cardiovascular control occurred early in the course of PD. They also provided
      evidence that the side effects of L-dopa aggravated the impairment of the
      autonomic control of BP and HR.

PMID- 15556836
TI  - Heart rate variability in patients with different manifestations of
      gastroesophageal reflux disease.
AB  - BACKGROUND: Autonomic nervous dysfunction has frequently been observed in
      patients with gastroesophageal reflux diseases (GERD) and impacts the
      pathogenesis of GERD. However, the characteristics that distinguish between GERD
      patients with different manifestations remain unknown. AIM: To investigate the
      autonomic nervous function in subgroups of GERD patients. PATIENTS: Of the 164
      participants in this study, 57 were healthy controls, 34 had non-erosive reflux
      disease (NERD), 40 had symptomatic esophagitis (SE), and 33 asymptomatic
      esophagitis (AE). METHODS: Resting autonomic activity was assessed by measuring
      the 5-min heart rate variability (HRV) and HRV indices including time-domain
      parameters (standard deviation of normal-to-normal intervals [SDNN] and root mean
      square of successive differences [RMSSD]) and frequency-domain parameters (low
      frequency power [LF; 0.04-0.15 Hz], high-frequency power [HF; 0.15-0.4 Hz], and
      LF/HF power ratio). Mental stress was assessed by use of a self-reported
      questionnaire (Brief Symptom Rating Scale [BSRS]). RESULTS: HF power was (ANOVA,
      p=0.041) but time-domain parameters, LF power, LF/HF power ratio, and BSRS
      parameters were not significantly different between the four groups. A higher HF
      power was found in examinees with NERD than in those with SE and AE (LSD methods:
      both p=0.02). When split into two groups (erosive vs. non-erosive), nearly all
      measures of autonomic tonus were significantly lower in the erosive than non
      erosive group. Age and the presence of endoscopic esophagitis influenced the
      RMSSD and HF power results in the regression analysis. Mental stress or gender
      did not correlate with any HRV index. CONCLUSION: In comparison with NERD
      subjects, autonomic tonus in patients with endoscopically confirmed esophagitis
      (even without symptom) is lower. This finding may suggest that the structural
      state of esophagus but not symptomatology dictates autonomic function status.

PMID- 15556837
TI  - Differences in autonomic responses between subjects with and without nausea while
      watching an irregularly oscillating video.
AB  - Prodromal signs such as cardiac rhythm disturbance and changes in gastric
      motility are generally induced before and during nausea in humans. These
      autonomic reactions were compared in subjects who were or were not experiencing
      nausea. Nausea was induced by having the subjects view a movie of oscillating
      pictures. Seventeen healthy volunteers were asked to relax their muscles and
      watch the movie. Electrogastrogram (EGG), electrocardiogram (ECG), palmar and
      metopic perspiration, digital blood flow and thoracic movement related to
      respiration were simultaneously measured while the subjects viewed the movie. A
      total of 11 of 17 subjects complained of nausea after watching the movie. The
      characteristic changes in their autonomic responses during exposure to the movie
      were as follows. The power of the EGG, heart rate and metopic perspiration
      significantly increased compared to those before watching the movie. The
      respiratory cycle gradually increased during and even after watching the movie.
      In contrast, no significant changes in the power of the EGG, heart rate and
      metopic perspiration were observed in the remaining six subjects who did not
      experience nausea. The role of the autonomic nervous system in nausea is
      discussed. These results suggest that these symptoms regarding the sympathetic
      nervous system could actually be defensive reactions against the sensation of
      nausea.

PMID- 15556838
TI  - Orthostatic challenge does not alter skin sympathetic nerve activity in heat
      stressed humans.
AB  - Perturbations that load or unload baroreceptors do not alter skin sympathetic
      nerve activity (SSNA) in normothermic individuals. However, in pronounced heat
      stressed individuals, when a significant component of the SSNA signal is
      sudomotor and possibly vasodilator in origin, the effects of baroreceptor
      unloading via an orthostatic stress on SSNA remain unclear. The purpose of the
      present study was to test the hypothesis that low and moderate levels of
      orthostatic stress via lower body negative pressure (LBNP) alter SSNA in
      pronounced heat-stressed individuals. In both normothermic and heat-stressed
      conditions, progressive LBNP at -3, -6, -9, -12, -15, -18, -21 and -40 mm Hg were
      applied to 11 subjects for 2 min per stage. Whole-body heating increased
      sublingual temperature by 0.7+/-0.1 degrees C, heart rate by 28+/-2.1 bpm, SSNA
      by 259+/-76 %, forearm skin blood flow by 631+/-142% and forearm sweat rate to
      0.68+/-0.14 mg/cm(2)/min (all p<0.005), but did not change mean arterial blood
      pressure (MAP) (p>0.05). LBNP did not change total SSNA in normothermic or heat
      stressed conditions (both p>0.05), although skin blood flow and sweat rate
      decreased during moderate levels of LBNP while heat stressed. These data suggest
      that in pronounced heat-stressed individuals, when a significant component of the
      SSNA signal contains sudomotor and possibly cutaneous active vasodilator
      activities, low and moderate levels of baroreceptor unloading via LBNP do not
      alter total SSNA. This observation, coupled with reductions in skin blood flow
      and sweating during moderate levels of LBNP, suggests that integrated SSNA should
      not be used as an indicator of baroreflex modulation of the cutaneous vasculature
      or sweat rate in heat-stressed subjects.

PMID- 15556839
TI  - Laser Doppler-recorded venoarteriolar reflex in Raynaud's phenomenon.
AB  - The aim of the study was to assess whether Laser Doppler-recorded venoarteriolar
      reflex (VAR) response to hand lowering can contribute to differentiate primary
      from secondary Raynaud's phenomena. MATERIALS AND METHODS: Skin fingerpulp
      perfusion (PU) of each hand of 60 persons was investigated: 15 healthy controls;
      15 primary Raynaud's phenomenon (RP) patients; 15 patients with Raynaud's
      phenomenon secondary to systemic sclerosis (SSc); 15 patients with Raynaud's
      phenomenon secondary to vibration exposure. Blood perfusion was monitored by
      Laser Doppler flowmetry (LDF) as initial values and at a temperature of 32
      degrees C with hands on the sternum (PUh) and in dependency (PUd). VAR indices
      were analyzed: delta VAR (DeltaVAR) calculated as (PUd-PUh); percent change of
      perfusion--[(DeltaVAR/PUh) x 100]; and vasoconstriction response--(PUd/PUh).
      RESULTS: Initial mean superficial skin temperatures and perfusions in Raynaud's
      phenomenon groups were significantly lower compared to healthy controls but with
      wide overlap of the values in individual cases. Venoarteriolar indices were
      significantly different between secondary Raynaud's phenomenon groups and healthy
      controls and between secondary and primary Raynaud's phenomenon groups. Percent
      changes were significantly higher in control and primary RP groups compared to
      secondary RP groups. Vasoconstriction indices between primary and secondary RP
      patients (p<0.0001) and between controls and secondary RP patients (p<0.0001)
      also differed. A loss of venoarteriolar reflex (DeltaPU>or=0) was established in
      10.0% of primary, 53.3% of sclerodermic, and 36.7% of vibration-induced Raynaud's
      phenomenon patients. The significantly higher prevalence rate of impaired
      venoarteriolar reflex in secondary Raynaud's phenomenon patients proves local
      vasomotor dysfunction and reflects either postganglionar sympathetic
      insufficiency with vascular tone failure or altered smooth muscle cells'
      responses. CONCLUSIONS: Laser Doppler flowmetry is a valuable noninvasive method
      for investigation of the very early skin venoarteriolar dysfunctions, for
      evaluation of focal autonomic dysregulation and skin vasomotor abnormalities in
      RP patients. Laser Doppler-recorded venoarteriolar reflex testing is a simple
      procedure and an adequate additional diagnostic tool, which contributes to
      diagnose RP and differentiate primary from secondary RP.

PMID- 15556840
TI  - Comparison of heart rate variability and stroke volume variability.
AB  - In order to compare the heart rate variability (HRV) and stroke volume
      variability (SVV), supine electrocardiographic (ECG) and the time series data of
      left ventricular (LV) volume recordings were taken in 12 healthy adult male
      volunteers. The low frequency (LF) and high frequency (HF) peaks of HRV and SVV
      were evaluated quantitatively by power spectral analysis. The fractal dimension
      (FD) of the time series data was analyzed by the box-counting method. A LF peak
      around 0.1 Hz and a HF peak around 0.3 Hz were as clearly observed in the SVV
      spectrum as in the HRV spectrum. The LF/HF ratio in SVV was significantly lower
      than that in HRV, while the FD was significantly higher in SVV than in HRV. No
      significant correlation of HF, LF or FD was observed between HRV and SVV. Our
      results indicate that SVV provides different information about the activity of
      the autonomic nervous system than HRV.

PMID- 15556841
TI  - Orthostatic modification of ventilatory dynamic response to carbon dioxide
      perturbations.
AB  - In order to determine whether changes in ventilatory control contribute to the
      observed decrease in arterial partial pressure of carbon dioxide (PaCO(2)) during
      head up tilt, we assessed ventilatory dynamic sensitivity to changes in PaCO(2)
      during supine and 70 degrees passive head up tilt. In 24 adult normals, we
      stimulated the ventilatory control system by switching inspired CO(2) between
      room air and room air+5% CO(2) in a pseudo random binary sequence. A Box-Jenkins
      model was used to compute ventilatory response to CO(2). Airflow, CO(2), non
      invasive beat by beat blood pressure, ECG and cerebral blood flow velocity
      (Doppler) were recorded. During tilt, sensitivity of the ventilatory controller
      to CO(2) disturbance increased (from 0.45 to 0.72 L/min/mm Hg, p<0.005); minute
      ventilation increased (7.63 to 8.47 L/min, p<0.01), end tidal CO(2) (ETCO(2)),
      cerebral blood flow velocity (CBF) and baroreflex sensitivity decreased (46.9 to
      42.9 mm Hg, p<0.001; 84.9 to 72.9 cm/s, p<0.001; and 17.6 to 5.5 ms/mm Hg,
      p<0.001). The primary observation from our study was that the sensitivity of
      ventilatory control system to perturbations in ETCO(2) increased during tilt.
      Taken together with decrease in mean levels of ETCO(2) and an increase in minute
      ventilation, these results suggest that during tilt, a change in the regulated
      level or 'set point' of PaCO(2) may occur.

PMID- 15556842
TI  - Effects of perivagal administration of capsaicin on food intake in animals after
      noxious gastric surgery.
AB  - Previous studies have shown that the perivagal administration of capsaicin
      induces greater food intake vs. controls at 24 h after the surgery but a similar
      intake to that of controls at 48 h. The present study aimed to determine whether
      the nutritive effect observed after perivagal capsaicin administration is due to
      the interruption of noxious vagal fibers in rats. For this purpose, postsurgical
      food intake was analyzed in control and capsaicin-treated animals with
      (Experiment 2) and without (Experiment 1) noxious lesions in the gastric wall.
      The results of both experiments showed that the food intake of capsaicin-treated
      animals was greater vs. control animals at 24 h but not at 48 h after the surgery
      (p<0.025), as previously demonstrated. However, the food intake of the capsaicin
      treated lesion animals in Experiment 2, although still greater than that of the
      control group, was significantly less than the intake of the capsaicin-treated
      animals in Experiment 1 (p<0.01). Therefore, it appears unlikely that the
      demonstrated effect is produced by lesion to noxious vagal fibers destroyed by
      the capsaicin. On the contrary, it is more likely that the vagal afferent
      pathways are those related to short-term nutrition.

PMID- 15556843
TI  - UN stalls on human cloning.
AB  - The United Nations postponed again a controversial vote on the issue of
      therapeutic cloning of human stem cells, hampering the widely supported
      opposition to reproductive cloning but many countries are developing their own
      legislation.

PMID- 15556845
TI  - Roger Carpenter.
AB  - Roger Carpenter is Reader in Oculomotor Physiology at the University of
      Cambridge. His main research interest is eye movements, and especially the neural
      decision mechanisms that determine where you look. He is the author of Movements
      of the Eyes as well as of the highly successful textbook Neurophysiology. In 2000
      he was one of the inaugural winners of a national teaching prize.

PMID- 15556846
TI  - Cliff hangers.

PMID- 15556847
TI  - Cavefish.

PMID- 15556848
TI  - Placozoa -- no longer a phylum of one.

PMID- 15556849
TI  - Capsaspora owczarzaki is an independent opisthokont lineage.

PMID- 15556850
TI  - Organogenesis: cutting to the chase.
AB  - Gonad morphogenesis in Caenorhabditis elegans requires two secreted proteases.
      Recent studies show that alterations of the extracellular matrix component
      fibulin-1 rescue gonadogenesis in the absence of these proteases. This finding is
      a critical step toward understanding the role of extracellular matrix in
      organogenesis.

PMID- 15556851
TI  - Eye movements: viewing the window of opportunity.
AB  - When searching with our eyes, parallel programming of successive eye movements
      ensures that visual information arriving too late to alter the direction of one
      eye movement can still influence the direction of the next. Paradoxically, we can
      use random noise to probe the time period over which visual information
      influences where next to direct our gaze.

PMID- 15556852
TI  - Cytokinesis: the central spindle takes center stage.
AB  - The central spindle plays a key role in cytokinesis. Recent studies have shed new
      light on how assembly of the central spindle is regulated, and also support a
      role for both the central spindle and astral microtubules in cytokinesis in
      animal cells.

PMID- 15556853
TI  - Evolution and development: rise of the little squirts.
AB  - It used to be thought that only vertebrates possess neural crest cells, but a
      recent study has demonstrated the existence of neural crest-like cells in an
      ascidian urochordate. This alters our views on the evolution of the neural crest
      and of the vertebrates.

PMID- 15556854
TI  - Acrosomal actin: twists and turns of a versatile filament.
AB  - A new electron cryomicroscopic reconstruction of an actin-scruin bundle from
      Limulus sperm reveals details about the enormous structural plasticity within F
      actin. The twist and tilt of the actin subunits show very large deviations from
      ideal F-actin, providing clues about actin dynamics.

PMID- 15556855
TI  - Meiotic recombination: sealing the partnership at the junction.
AB  - Crossovers ensure proper chromosome segregation in meiosis. A heterodimer of MutS
      proteins, hMSH4-hMSH5, has recently been found to interact with recombination
      intermediates in a manner that suggests a mechanism for directing meiotic DNA
      double strand break repair towards a crossover pathway.

PMID- 15556856
TI  - Dendritic cells: the bare bones of immunity.
AB  - Dendritic cells are specialized antigen-presenting cells, critical for initiating
      and regulating immune responses. Two new studies demonstrate the importance of
      coordinated cytoskeletal regulation for their normal function.

PMID- 15556857
TI  - Membrane traffic: controlling membrane fusion by modifying NSF.
AB  - Recent studies show that NSF, isolated over 15 years ago as a protein required
      for membrane fusion in vitro, can be reversibly inactivated by both S
      nitrosylation and tyrosine phosphorylation. Different cell types use distinct
      post-translational modifications of NSF for localized regulation of membrane
      fusion.

PMID- 15556858
TI  - Molecular motors: strategies to get along.
AB  - The majority of active transport in the cell is driven by three classes of
      molecular motors: the kinesin and dynein families that move toward the plus-end
      and minus-end of microtubules, respectively, and the unconventional myosin motors
      that move along actin filaments. Each class of motor has different properties,
      but in the cell they often function together. In this review we summarize what is
      known about their single-molecule properties and the possibilities for regulation
      of such properties. In view of new results on cytoplasmic dynein, we attempt to
      rationalize how these different classes of motors might work together as part of
      the intracellular transport machinery. We propose that kinesin and myosin are
      robust and highly efficient transporters, but with somewhat limited room for
      regulation of function. Because cytoplasmic dynein is less efficient and robust,
      to achieve function comparable to the other motors it requires a number of
      accessory proteins as well as multiple dyneins functioning together. This
      necessity for additional factors, as well as dynein's inherent complexity, in
      principle allows for greatly increased control of function by taking the factors
      away either singly or in combination. Thus, dynein's contribution relative to the
      other motors can be dynamically tuned, allowing the motors to function together
      differently in a variety of situations.

PMID- 15556859
TI  - Partial nuclear pore complex disassembly during closed mitosis in Aspergillus
      nidulans.
AB  - BACKGROUND: Many organisms undergo closed mitosis and locate tubulin and mitotic
      kinases to nuclei only during mitosis. How this is regulated is unknown.
      Interestingly, the NIMA kinase of Aspergillus nidulans interacts with two nuclear
      pore complex (NPC) proteins and NIMA is required for mitotic localization of the
      Cdk1 kinase to nuclei. Therefore, we wished to define the mechanism by which the
      NPC is regulated during A. nidulans' closed mitosis. RESULTS: The structural
      makeup of the NPC is dramatically changed during A. nidulans' mitosis. At least
      five NPC proteins disperse throughout the cell during mitosis while at least
      three structural components remain at the NPC. These modifications correlate with
      marked changes in the function of the NPC. Notably, during mitosis, An-RanGAP is
      not excluded from nuclei, and five other nuclear or cytoplasmic proteins
      investigated fail to locate as they do during interphase. Mitotic modification of
      the NPC requires NIMA and Cdk1 kinase activation. NIMA appears to be particularly
      important. Most strikingly, ectopic induction of NIMA promotes mitotic-like
      changes in NPC structure and function during S phase. Furthermore, NIMA locates
      to the NPC during entry into mitosis, and a dominant-negative version of NIMA
      that causes G2 delay dwells at the NPC. CONCLUSIONS: We conclude that partial NPC
      disassembly under control of NIMA and Cdk1 in A. nidulans may represent a new
      mechanism for regulating closed mitoses. We hypothesize that proteins locate by
      their relative binding affinities within the cell during A. nidulans' closed
      mitosis, analogous to what occurs during open mitosis.

PMID- 15556860
TI  - Guide RNAs with 5' caps and novel box C/D snoRNA-like domains for modification of
      snRNAs in metazoa.
AB  - BACKGROUND: Spliceosomal snRNAs and ribosomal RNAs in metazoans contain numerous
      modified residues that are functionally important. The most common modifications
      are site-specific 2'-O-methylation and pseudouridylation, both directed by small
      ribonucleoprotein particles. Each particle is composed of a short guide RNA and a
      set of several proteins. All previously characterized modification guide RNAs in
      metazoa are encoded in and processed from introns. RESULTS: We have identified
      and characterized three novel guide RNAs for conserved 2'-O-methylation of U2,
      U4, and U12 snRNAs. Two guides, termed mgU2-25/61 and mgU12-22/U4-8, appear to be
      independently transcribed as judged by the presence of methylated guanosine caps
      at their 5' ends and upstream promoters similar to those of telomerase RNA. These
      guide RNAs are each composed of a canonical box C/D snoRNA and a novel box C/D
      snoRNA-like domain, where the C'/D' motif, rather than C/D, can be folded into a
      conserved kink-turn structure. The snoRNA-like domains are predicted to direct 2'
      O-methylation of invariant G residues that occupy analogous positions in the U2
      and U12 snRNA secondary structures. A third guide, mgU2-19/30 RNA, is composed of
      two canonical box C/D snoRNA domains encoded within a single intron. CONCLUSIONS:
      This is the first description in metazoan cells of 5'-capped modification guide
      RNAs that appear to be independently transcribed. Since plant, yeast, and
      protozoan guide RNAs are mostly independently transcribed, the identification of
      such RNAs argues that ancestral metazoans possessed independently transcribed
      guide RNAs and only later, during the evolution of metazoan organisms, did the
      guide RNA genes shift to introns.

PMID- 15556861
TI  - Live cell imaging of mitochondrial movement along actin cables in budding yeast.
AB  - BACKGROUND: Mitochondrial inheritance is essential for cell division. In budding
      yeast, mitochondrial movement from mother to daughter requires (1) actin cables,
      F-actin bundles that undergo retrograde movement during elongation from buds into
      mother cells; (2) the mitochore, a mitochondrial protein complex implicated in
      linking mitochondria to actin cables; and (3) Arp2/3 complex-mediated force
      generation on mitochondria. RESULTS: We observed three new classes of
      mitochondrial motility: anterograde movement at velocities of 0.2-0.33 microm/s,
      retrograde movement at velocities of 0.26-0.51 microm/s, and no net anterograde
      or retrograde movement. In all cases, motile mitochondria were associated with
      actin cables undergoing retrograde flow at velocities of 0.18-0.62 microm/s.
      Destabilization of actin cables or mutations of the mitochore blocked all
      mitochondrial movements. In contrast, mutations in the Arp2/3 complex affected
      anterograde but not retrograde mitochondrial movements. CONCLUSIONS: Actin cables
      are required for movement of mitochondria, secretory vesicles, mRNA, and spindle
      alignment elements in yeast. We provide the first direct evidence that one of the
      proposed cargos use actin cables as tracks. In the case of mitochondrial
      inheritance, anterograde movement drives transfer of the organelle from mothers
      to buds, while retrograde movement contributes to retention of the organelle in
      mother cells. Interaction of mitochondria with actin cables is required for
      anterograde and retrograde movement. In contrast, force generation on
      mitochondria is required only for anterograde movement. Finally, we propose a
      novel mechanism in which actin cables serve as "conveyor belts" that drive
      retrograde organelle movement.

PMID- 15556862
TI  - GON-1 and fibulin have antagonistic roles in control of organ shape.
AB  - Most developing organs are surrounded by an extracellular matrix (ECM), which
      must be remodeled to accommodate growth and morphogenesis. In C. elegans, the GON
      1 ADAMTS metalloprotease regulates both elongation and shape of the developing
      gonad . Here, we report that either human ADAMTS-4 or ADAMTS-9 can substitute for
      GON-1 in transgenic worms, suggesting functional conservation between human and
      nematode homologs. We further identify fibulin (FBL-1), a widely conserved ECM
      component , as critical for gonadal morphogenesis. FBL-1 is expressed in
      nongonadal tissues but is present at the surface of the elongating gonad. A
      fibulin deletion mutant has a wider than normal gonad as well as body size
      defects. We find that GON-1 and fibulin have antagonistic roles in controlling
      gonadal shape. Depletion of fbl-1, but not other ECM components, rescues gon-1
      elongation defects, and removal of gon-1 rescues fbl-1 width defects. Therefore,
      the GON-1 protease normally promotes tissue elongation and expansion, whereas the
      fibulin ECM protein blocks these key morphogenetic processes. We suggest that
      control of organ shape by GON-1 and fibulin in C. elegans may provide a model for
      similar cellular processes, including vasculogenesis, in humans.

PMID- 15556863
TI  - A fibulin-1 homolog interacts with an ADAM protease that controls cell migration
      in C. elegans.
AB  - ADAM (a disintegrin and metalloprotease) family proteins play important roles in
      animal development and pathogenesis. In C. elegans, a secreted ADAM protein, MIG
      17, acts from outside the gonad to control the migration of gonadal distal tip
      cells (DTCs) that promote gonad morphogenesis. Here, we report that dominant
      mutations in the fbl-1 gene encoding fibulin-1 spliced isoforms, which are
      calcium binding extracellular matrix proteins, bypass the requirement for MIG-17
      activity in directing DTC migration. Specific amino acid substitutions in the
      third EGF-like motif of one of the two isoforms, FBL-1C, which corresponds to
      mammalian fibulin-1C, suppress mig-17 mutations. FBL-1C is synthesized in the gut
      cells and localizes strongly to the gonadal basement membrane in a MIG-17
      dependent manner. Localization of mutant FBL-1C is weaker than that of the wild
      type protein and is insensitive to MIG-17 activity, suggesting that it gains a
      novel function that compensates for its reduced molecular density. We propose
      that proteolysis by MIG-17 recruits FBL-1C to the gonadal basement membrane,
      where it is required for the guidance of DTCs, and that mutant FBL-1C acts in a
      manner that mimics the downstream events of MIG-17-mediated proteolysis.

PMID- 15556864
TI  - The mitotic arrest in response to hypoxia and of polar bodies during early
      embryogenesis requires Drosophila Mps1.
AB  - Mps1 kinase plays an evolutionary conserved role in the mitotic spindle
      checkpoint. This system precludes anaphase onset until all chromosomes have
      successfully attached to spindle microtubules via their kinetochores. Mps1
      overexpression in budding yeast is sufficient to trigger a mitotic arrest, which
      is dependent on the other mitotic checkpoint components, Bub1, Bub3, Mad1, Mad2,
      and Mad3. Therefore, Mps1 might act at the top of the mitotic checkpoint cascade.
      Moreover, in contrast to the other mitotic checkpoint components, Mps1 is
      essential for spindle pole body duplication in budding yeast. Centrosome
      duplication in mammalian cells might also be controlled by Mps1 , but the fission
      yeast homolog is not required for spindle pole body duplication. Our phenotypic
      characterizations of Mps1 mutant embryos in Drosophila do not reveal an
      involvement in centrosome duplication, while the mitotic spindle checkpoint is
      defective in these mutants. In addition, our analyses reveal novel functions. We
      demonstrate that Mps1 is also required for the arrest of cell cycle progression
      in response to hypoxia. Finally, we show that Mps1 and the mitotic spindle
      checkpoint are responsible for the developmental cell cycle arrest of the three
      haploid products of female meiosis that are not used as the female pronucleus.

PMID- 15556865
TI  - APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and
      establishment of neuronal polarity.
AB  - In developing hippocampal neurons in culture, the evolutionarily conserved
      polarity complex mPar3/mPar6/aPKC selectively accumulates at the tip of one, and
      only one, of the immature neurites of a neuron and thus specifies the axon and
      generates neuronal polarity. How mPar3/mPar6 is enriched at the tip of the
      nascent axon, but not the dendrites, is not fully understood. Here, we report
      that mPar3 forms a complex with adenomatous polyposis coli (APC) and kinesin
      superfamily (KIF) 3A, proteins that move along microtubules. In polarizing
      hippocampal neurons, APC selectively accumulates at the nascent axon tip and
      colocalizes with mPar3. Expression of dominant-negative C terminus deletion
      mutants of APC or ectopic expression of APC leads to dislocalization of mPar3 and
      defects in axon specification and neuronal polarity. In addition to spatial
      polarization of APC, the selective inactivation of the GSK-3beta activity at the
      nascent axon tip is required for mPar3 targeting and polarization and
      establishing neuronal polarity. These results suggest that mPar3 is polarized in
      developing neurons through APC- and kinesin-mediated transport to the plus ends
      of rapidly growing microtubules at the nascent axon tip, a process that involves
      a spatially regulated GSK-3beta activity.

PMID- 15556866
TI  - Adenomatous polyposis coli associates with the microtubule-destabilizing protein
      XMCAK.
AB  - During cell division, the proper formation of a bipolar spindle and its function
      to segregate chromosomes requires precise coordination of microtubule-stabilizing
      and destabilizing activities. Globally destabilized, dynamic microtubules
      radiating from duplicated centrosomes are locally regulated by chromosomes.
      Proteins at the kinetochore of each sister chromatid mediate a dynamic
      attachment, allowing chromosome movement coupled to microtubule
      polymerization/depolymerization and error-correction mechanisms for improperly
      attached chromosomes. The tumor suppressor protein adenomatous polyposis coli
      (APC) stabilizes microtubules both in vitro and in vivo and is implicated in
      mitosis, although its mechanisms of action are not well characterized. Here, we
      show that in mitotic Xenopus egg extracts, the carboxyl-terminus of APC can
      associate with the amino terminus of the microtubule-destabilizing KinI, Xenopus
      mitotic centromere-associated kinesin (XMCAK), in a cytoplasmic complex. We find
      that like XMCAK, APC can localize to the centromere as well as the kinetochore
      region of mitotic chromosomes and does not require microtubules for chromosomal
      targeting in Xenopus egg extracts. We propose that the presence of these proteins
      in a complex brings together both positive and negative microtubule effectors,
      whose opposing activities may be regulated by additional factors, thereby
      providing precise control of both global and local microtubule dynamics.

PMID- 15556867
TI  - glaikit is essential for the formation of epithelial polarity and neuronal
      development.
AB  - Epithelial cells have a distinctive polarity based on the restricted distribution
      of proteins and junctional complexes along an apical-basal axis. Studying the
      formation of the polarized ectoderm of the Drosophila embryo has identified a
      number of the molecules that establish this polarity. The Crumbs (Crb) complex is
      one of three separate complexes that cooperate to control epithelial polarity and
      the formation of zonula adherens. Here we show that glaikit (gkt), a member of
      the phospholipase D superfamily, is essential for the formation of epithelial
      polarity and for neuronal development during Drosophila embryogenesis. In
      epithelial cells, gkt acts to localize the Crb complex of proteins to the apical
      lateral membrane. Loss of gkt during neuronal development leads to a severe CNS
      architecture disruption that is not dependent on the Crb pathway but probably
      results from the disrupted localization of other membrane proteins. A mutation in
      the human homolog of gkt causes the neurodegenerative disease spinocerebellar
      ataxia with neuropathy (SCAN1), making it possible that a failure of membrane
      protein localization is a cause of this disease.

PMID- 15556868
TI  - Inturned localizes to the proximal side of wing cells under the instruction of
      upstream planar polarity proteins.
AB  - Planar polarity development in the Drosophila wing is under the control of the
      frizzled (fz) pathway. Recent work has established that the planar polarity (PP)
      proteins become localized to either the distal, proximal, or both sides of wing
      cells. Fz and Dsh distal accumulation is thought to locally activate the
      cytoskeleton to form a hair . Planar polarity effector (PPE) genes such as
      inturned (in) are not required for the asymmetric accumulation of PP proteins,
      but they are required for this to influence hair polarity. in mutations result in
      abnormal hair polarity and are epistatic to mutations in the PP genes. We report
      that In localizes to the proximal side of wing cells in a PP-dependent and PP
      instructive manner. We further show that the function of two other PPE genes
      (fuzzy and fritz) is essential for In protein localization, a finding consistent
      with previous genetic data that suggested these three genes function in a common
      process. These data indicate that accumulation of proteins at the proximal side
      of wing cells is a key event for the distal activation of the cytoskeleton to
      form a hair.

PMID- 15556869
TI  - Atypical mechanism of regulation of the Wrch-1 Rho family small GTPase.
AB  - Rho family GTPases are GDP/GTP-regulated molecular switches that regulate
      signaling pathways controlling diverse cellular processes. Wrch-1 was identified
      as a Wnt-1 regulated Cdc42 homolog, upregulated by Wnt1 signaling in Wnt1
      transformed mouse mammary cells, and was able to promote formation of filopodia
      and activate the PAK serine/threonine kinase. Wrch-1 shares significant sequence
      and functional similarity with the Cdc42 small GTPase. However, Wrch-1 possesses
      a unique N-terminal 46 amino acid sequence extension that contains putative Src
      homology 3 (SH3) domain-interacting motifs. We determined the contribution of the
      N terminus to Wrch-1 regulation and activity. We observed that Wrch-1 possesses
      properties that distinguish it from Cdc42 and other Rho family GTPases. Unlike
      Cdc42, Wrch-1 possesses an extremely rapid, intrinsic guanine nucleotide exchange
      activity. Although the N terminus did not influence GTPase or GDP/GTP cycling
      activity in vitro, N-terminal truncation of Wrch-1 enhanced its ability to
      interact with and activate PAK and to cause growth transformation. The N terminus
      associated with the Grb2 SH3 domain-containing adaptor protein, and this
      association increased the levels of active Wrch-1 in cells. We propose that Grb2
      overcomes N-terminal negative regulation to promote Wrch-1 effector interaction.
      Thus, Wrch-1 exhibits an atypical model of regulation not seen in other Rho
      family GTPases.

PMID- 15556870
TI  - The anaphase-promoting complex regulates the abundance of GLR-1 glutamate
      receptors in the ventral nerve cord of C. elegans.
AB  - The anaphase-promoting complex (APC) is a multisubunit E3 ubiquitin ligase that
      targets key cell cycle regulatory proteins for degradation. Blockade of APC
      activity causes mitotic arrest. Recent evidence suggests that the APC may have
      roles outside the cell cycle. Several studies indicate that ubiquitin plays an
      important role in regulating synaptic strength. We previously showed that
      ubiquitin is directly conjugated to GLR-1, a C. elegans non-NMDA (N-methyl-D
      aspartate) class glutamate receptor (GluR), resulting in its removal from
      synapses. By contrast, endocytosis of rodent AMPA GluRs is apparently regulated
      by ubiquitination of associated scaffolding proteins. Relatively little is known
      about the E3 ligases that mediate these effects. We examined the effects of
      perturbing APC function on postmitotic neurons in the nematode C. elegans.
      Temperature-sensitive mutations in APC subunits increased the abundance of GLR-1
      in the ventral nerve cord. Mutations that block clathrin-mediated endocytosis
      blocked the effects of the APC mutations, suggesting that the APC regulates some
      aspect of GLR-1 recycling. Overexpression of ubiquitin decreased the density of
      GLR-1-containing synapses, and APC mutations blunted this effect. APC mutants had
      locomotion defects consistent with increased synaptic strength. This study
      defines a novel function for the APC in postmitotic neurons.

PMID- 15556871
TI  - An Mll-dependent Hox program drives hematopoietic progenitor expansion.
AB  - Chromosomal translocations disrupting the Mixed lineage leukemia (Mll) gene
      result in leukemia, with aberrant expression of some native Mll target genes
      (reviewed in). The Mll gene encodes a Trithorax-group chromatin regulator that is
      essential for the development of hematopoietic stem cells (HSCs) during
      embryogenesis. Like Trithorax, MLL positively regulates clustered homeodomain or
      Hox genes, yet the role of Hox genes collectively in the development of the
      mammalian hematopoietic system has been difficult to ascertain because of
      redundancy among Hox paralogs. Here, we show that in the absence of MLL, early
      hematopoietic progenitors develop despite reduced expression of HoxA, HoxB, and
      HoxC genes. However, these progenitors exhibit a marked reduction in their
      ability to generate hematopoietic colonies, a subsequent process requiring cell
      division and differentiation. Reactivation of a subset of Hox genes or,
      remarkably, reexpression of a single Hox gene in Mll-deficient progenitors
      rescued hematopoietic-colony frequency and growth. In contrast, expression of
      other MLL target genes such as Pitx2 or expression of anti-apoptotic BCL-2 failed
      to rescue hematopoietic-colony frequency. Furthermore, our results highlight a
      shared function of Hox proteins at this point in the development of the
      hematopoietic system.

PMID- 15556872
TI  - Novel assembly properties of recombinant spider dragline silk proteins.
AB  - Spider dragline silk, which exhibits extraordinary strength and toughness, is
      primarily composed of two related proteins that largely consist of repetitive
      sequences. In most spiders, the repetitive region of one of these proteins is
      rich in prolines, which are not present in the repetitive region of the other.
      The absence of prolines in one component was previously speculated to be
      essential for the thread structure. Here, we analyzed dragline proteins of the
      garden spider Araneus diadematus, ADF-3 and ADF-4, which are both proline rich,
      by employing the baculovirus expression system. Whereas ADF-3 represented an
      intrinsically soluble protein, ADF-4 was insoluble in vitro and self-assembled
      into filaments in the cytosol of the host insect cells. These ADF-4 filaments
      displayed the exceptional chemical stability of authentic silk threads. We
      provide evidence that the observed properties of ADF-3 and ADF-4 strongly depend
      on intrinsic characteristics such as hydropathicity, which differs dramatically
      between the two proteins, as in most other pairs of dragline silk proteins from
      other Araneoidea species, but not on their proline content. Our findings shed new
      light on the structural components of spider dragline silk, allowing further
      elucidation of their assembly properties, which may open the door for commercial
      applications.

PMID- 15556873
TI  - [The Lasker Prize and the 2004 Nobel Prize in Chemistry for the regulation of
      genes from A to Z].

PMID- 15556875
TI  - [Molecular mechanisms involved in hormone resistance of prostate cancer].
AB  - Prostate cancer has an androgen-dependent growth mediated by the androgen
      receptor (AR). Androgen pathway blockage is the standard therapy for the
      treatment of prostate cancers at an advanced stage. In spite of an initial
      sensitivity, prostate cancers become more or less quickly towards androgen
      independent. Hormone refractory can be due to amplification of AR gene, AR
      mutations and the increase in co-activator protein expression or in the 5alpha
      reductase activity. These induce an agonist activity with the anti-androgens or
      others steroid hormones like estrogens on AR and allow AR activation with weak
      concentrations of androgens. Growth factors and cytokines can induce AR
      phosphorylation independently of the ligand fixation. In condition of androgenic
      deprivation, AR remains actively involved in the growth of the cancerous cells
      prostate. Nevertheless, there are others partial AR-independent pathways as
      neuroendocrine differentiation. The comprehension of these various mechanisms is
      the key of the development of more effective therapies on hormono-refractory
      prostate cancers.

PMID- 15556876
TI  - [Clinical practice guideline: 2003 update of Standards, Options et
      Recommendations for first line palliative chemotherapy in patients with
      metastatic colorectal cancer (summary report)].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which
      started in 1993, is a collaboration between the Federation of French Cancer
      Centres (FNCLCC), the 20 French Regional Cancer Centres, and specialists from
      French public universities, general hospitals and private clinics. The main
      objective is the development of clinical practice guidelines to improve the
      quality of health care and the outcome of cancer patients. OBJECTIVES: To update
      clinical practice guidelines for first line palliative chemotherapy in patients
      with metastatic colorectal cancer previously validated in 1995, then updated in
      1997 and published again in 1998. These recommendations do not cover second line
      treatment. METHODS: The methodology is based on a literature review and critical
      appraisal by a multidisciplinary group of experts who define the CPGs according
      to the definitions of the Standards, Options and Recommendations project. Once
      the guidelines have been developed, they are reviewed by independent reviewers.
      RESULTS: This article is a summary version of the updated clinical practice
      guidelines with algorithms. The main questions addressed by the expert group in
      this update concerned (1) Which patients should be treated? (2) What is the best
      treatment duration? (3) Which treatment should be administered? The new data
      identified concerning which patients to treat and the duration of treatment were
      consistent with the data presented in the initial report and did not modify the
      original recommendations from 1997. The new data available represent stronger
      evidence than those in the original report (Two good-quality meta-analyses
      published since 1997). A new guideline concerning patients who are 75 years old
      or more has been added. Concerning, the new evidence identified has modified the
      guidelines for the therapeutic schema to adopt from 1997. These modifications
      concern irinotecan, oxaliplatin, oral fluoropyrimidines and methotrexate.
      Treatment with irinotecan or oxaliplatin associated with continuous 5FU infusion,
      modulated with folinic acid (LV5FU2-like) has become a standard. The use of oral
      fluoropyrimidines has become an option for patients who refuse hospitalisation or
      treatment by infusion. The use of methotrexate combined with 5FU is no longer
      recommended.

PMID- 15556877
TI  - [Anticancer drugs off label used of: what do the experts think about?].
AB  - Anticancer drugs off label used in Tenon hospital were analysed by a panel of 12
      experts not working at Tenon hospital. They distinguished 3 groups of off-label
      prescribing according to scientific evidence, labelling anticancer drugs
      alternative in presence and patient's characteristics: justified off label used
      (62%), unjustified off label used (26%) and prescriptions for which no consensus
      had been reached between the experts (12%). Nineteen per cent of unjustified off
      label used had labelling alternative and 7% did not have anticancer drugs
      labelling alternative. Questions who experts had to answer to analyse drugs
      prescribing could be systematically asked when a chemotherapy is prescribed. It
      could allowed to take into account scientific, economic and ethical requirements.
      This method proposed by the local drug committee could be used to regulate
      economic resources and to justify financing of some expensive anticancer drugs.

PMID- 15556878
TI  - [Effects of treatments on serum vitamin E levels in lung cancer].
AB  - Previous evidence suggests that malignant tumours cause an decrease in the serum
      vitamin E level. We followed the serum alpha tocopherol in 55 lung cancer
      patients. The objective of the study was to evaluate the effects of treatments of
      lung cancer on serum vitamin E evolution. The vitamin E of patients
      symptomatically treated decreases from the first month and this decrease is
      significant (p < 0.001) in patients affected by SCLC and in those with NSCLC
      classified stage III and IV. The reduction of the vitamin E is also noted in the
      patients treated with chemotherapy (p < 0.001). Vitamin E levels improve
      gradually to reach standard values in the patients who followed a curative
      radiotherapy or benefited from the surgical ablation of the tumour. At 4 months
      after the surgical removal of the tumour, there was an increase in serum vitamin
      E concentrations and reached the normal values. This data indicates that surgical
      removal of lung cancer increases serum vitamin E concentrations compared to the
      baseline values possibly reflecting the relief of oxidative stress caused by
      malignant tumours.

PMID- 15556879
TI  - [Prevention practices and cancer screening among general practitioners in Picardy
      (France)].
AB  - In France, cancers are the leading causes of death in men and in women aged to 35
      to 65, and the cancer incidence in Picardy area is among the highest in France.
      General practitioners can play a key role in prevention and early detection of
      cancer. The aim of this study was to assess their current clinical practices
      concerning risk factors like tobacco, alcohol, diet, sun exposure and cancer
      screening. A questionnaire on primary prevention and cancer screening practices
      of general practitioners (GP) in the Picardy area was administered to 480 GP
      (31%). Questions concerned primary prevention (tobacco, alcohol, diet, sun
      exposure) and cancer screening (breast, uterine cervix, colon-rectum, prostate,
      other cancers). In addition, the GP were also interviewed on difficulties
      encountered in their practice and about their perception of the prevention
      actions. Smoking prevention is the best structured primary prevention action,
      unlike alcohol prevention and advice on diet seem to be more difficult
      strategies. We noted a great diversity for screening, even for cancers with a
      consensus, like breast, uterine cervix and colon-rectum cancers. Lot of
      physicians reported ordering prostatic specific antigen test (91%) but are only
      5% to have fecal occult blood tests. 83% of the GP screened their patients on
      skin cancer at least once a year. These findings suggest that general
      practitioners can play a key role in prevention and early detection of cancer,
      but have difficulties like lack of time, lack of expertise or non compliance of
      their patients.

PMID- 15556880
TI  - [Methodological and ethical quality in phase III cancer trials: role of the
      cooperative group].
AB  - Phase III clinical trials (CT) are carried out more and more often in a
      multicentric way, under the aegis of one or more cooperative groups (CG). The
      goal of this study was to analyze the influence of the GC on ethical quality (EQ)
      and methodological quality (MQ) in phase III cancer CT. EQ (Berdeu-score) and MQ
      (Jadad scale) were assessed for all CTs (n=231) published between 1999 and 2001
      in 10 international journals. The impact of CG on EQ and MQ was evaluated with an
      univariate analysis. 140 ECR (60.6%) were carried out under the aegis of a CG.
      There was no improvement of the MQ and EQ for the trials carried out under the
      aegis of a CG. The methodological score (Jadad) was of 9.9 +/- 1.15 for the CT-CG
      (+) and of 9.8 +/- 1.28 for the CT-GC (-) (p=0.7). The ethical score (Berdeu) was
      of 0.43 +/- 0.14 for the CT-CG (+) and of 0.40 +/- 0.11 for the CT-CG (-)
      (p=0.08). Interim analysis, defined stopping rules and independent monitoring
      were more frequent for the CT-CG (+) and were respectively 37.8% vs 15.4%, 20.7%
      vs 8.8%, 19.3 vs 6.6%. 31.9% of the CT-CG (-) and 19.3% of the CT-CG (+) were
      financed by industry (p=0.03). The CG have a major role to play in the protection
      of the patient in CT, because they monitored trials from the conception to the
      publication and communication of results.

PMID- 15556881
TI  - [Organization and impact of the multidisciplinary committee in oncology].
AB  - Medical practices in oncology are expected to be more and more multidisciplinary,
      yet few articles studied how this may be concretely applied. This article is
      describing the functioning of a multidisciplinary specialized committee in a rare
      tumor. 219 medical cases during 26 meetings between 09/04/2003 and 14/02/2004 had
      been studied. Discussions had been observed, described and studied qualitatively
      and quantitatively. At the time of a national plan has been launched to impose
      obligatory the consultation of such committees before any treatment strategy, two
      lessons can be drawn from this case study. On the one hand, it shows that a
      multidisciplinary committee may be an organizational tool facilitating the
      emergence of collective decisions, since it may facilitate the formulation and
      the discussion of alternative options (72 cases out of 219). More generally, to
      take treatment decisions, members of the committee exchange arguments that deal
      mostly with clinical and psychological condition of the patient (50 cases out of
      219), state-of-the-art knowledge (39 cases out of 219) and individual experience
      of the practitioners (33 cases out of 219). On the other hand, this article
      intends to underline that the creation of such committees cannot be considered as
      a sufficient condition to improve the quality of treatment decisions. Indeed,
      this case study shows that the quality of decisions does not only rely on the
      collective deliberation, but also on the individual and specific competencies of
      some members of the committee that other members admit.

PMID- 15556882
TI  - [Breaking "bad news" in oncology].

PMID- 15556883
TI  - Conserved deployment of genes during odontogenesis across osteichthyans.
AB  - Odontogenesis has only been closely scrutinized at the molecular level in the
      mouse, an animal with an extremely restricted dentition of only two types and one
      set. However, within osteichthyans many species display complex and extensive
      dentitions, which questions the extent to which information from the mouse is
      applicable to all osteichthyans. We present novel comparative molecular and
      morphological data in the rainbow trout (Oncorhynchus mykiss) that show that
      three genes, essential for murine odontogenesis, follow identical spatial
      temporal expression. Thus, at all tooth bud sites, epithelial genes Pitx-2 and
      Shh initiate the odontogenic cascade, resulting in dental mesenchymal Bmp-4
      expression, importantly, including the previously unknown formation of
      replacement teeth. Significantly, this spatial-temporal sequence is the same for
      marginal and lingual dentitions, but we find notable differences regarding the
      deployment of Pitx-2 in the developing pharyngeal dentition. This difference may
      be highly significant in relation to the theory that dentitions may have evolved
      from pharyngeal tooth sets in jawless fishes. We have provided the first data on
      operational genes in tooth development to show that the same signalling genes
      choreograph this evolutionary stable event in fishes since the osteichthyan
      divergence 420 Myr ago, with the identical spatial-temporal expression as in
      mammals.

PMID- 15556884
TI  - Colour constancy under simultaneous changes in surface position and illuminant.
AB  - Two kinds of constancy underlie the everyday perception of surface colour:
      constancy under changes in illuminant and constancy under changes in surface
      position. Classically, these two constancies seem to place conflicting demands on
      the visual system: to both take into account the region surrounding a surface and
      also discount it. It is shown here, however, that the ability of observers to
      make surface-colour matches across simultaneous changes in test-surface position
      and illuminant in computer-generated 'Mondrian' patterns is almost as good as
      across changes in illuminant alone. Performance was no poorer when the surfaces
      surrounding the test surface were permuted, or when information from a potential
      comparison surface, the one with the highest luminance, was suppressed. Computer
      simulations of cone-photoreceptor activity showed that a reliable cue for making
      surface-colour matches in all experimental conditions was provided by the ratios
      of cone excitations between the test surfaces and a spatial average over the
      whole pattern.

PMID- 15556885
TI  - Novel chromatic and structural biomarkers of diet in carotenoid-bearing plumage.
AB  - Previous attempts to establish a link between carotenoid-based plumage
      reflectance and diet have focused on spectral features within the human visible
      range (400-700 nm), particularly on the longer wavelengths (550-700 nm) that make
      these plumages appear yellow, orange or red. However, carotenoid reflectance
      spectra are intrinsically bimodal, with a less prominent but highly variable
      secondary reflectance peak at near-ultraviolet (UV; 320-400 nm) wavelengths
      visible to most birds but not to normal humans. Analysis of physical reflectance
      spectra of carotenoid-bearing plumages among trophically diverse tanagers
      (Thraupini, Emberizinae, Passeriformes) indicated that both the absolute and
      relative (to long visible wavelengths) amounts of short waveband (including UV)
      reflectance were lower in more frugivorous species. Striking modifications to the
      branched structure of feathers increased with frugivory. These associations were
      independent of phylogenetic relatedness, or other physical (specimen age, number
      of carotenoid-bearing patches) or ecological (body size, elevation) variables. By
      comparison, reflectance at longer visible wavelengths ('redness') was not
      consistently associated with diet. The reflectance patterns that distinguished
      frugivores should be more apparent to UV-sensitive birds than to UV-blind humans,
      but humans can perceive the higher plumage gloss produced by modified gross
      feather structure. Basic aspects of carotenoid chemistry suggest that increases
      in pigment concentration and feather dimensions reduce short waveband reflectance
      by the plumages of frugivores.

PMID- 15556886
TI  - The disadvantage of combinatorial communication.
AB  - Combinatorial communication allows rapid and efficient transfer of detailed
      information, yet combinatorial communication is used by few, if any, non-human
      species. To complement recent studies illustrating the advantages of
      combinatorial communication, we highlight a critical disadvantage. We use the
      concept of information value to show that deception poses a greater and
      qualitatively different threat to combinatorial signalling than to non
      combinatorial systems. This additional potential for deception may represent a
      strategic barrier that has prevented widespread evolution of combinatorial
      communication. Our approach has the additional benefit of drawing clear
      distinctions among several types of deception that can occur in communication
      systems.

PMID- 15556887
TI  - Thermal selection of PGM allozymes in newly founded populations of the
      thermotolerant vent polychaete Alvinella pompejana.
AB  - Alvinella pompejana lives on the top of chimneys at deep-sea hydrothermal vents
      of the East Pacific Rise. It is thought to be one of the most thermotolerant and
      eurythermal metazoans. Our experimental approach combines methods of population
      genetics and biochemistry, considering temperature as a potential selective
      factor. Phosphoglucomutase (Pgm-1 locus) is one of the most polymorphic loci of
      A. pompejana and exhibits four alleles, from which alleles 90 and 100 dominate
      with frequencies of approximately 0.5 in populations. Results from previous
      studies suggested that allele 90 might be more thermostable than allele 100.
      Significant genetic differentiation was found by comparing contrasted
      microhabitats, especially the young, still hot, versus older and colder chimneys,
      with allele 90 being at highest frequency on young chimneys. Moreover the
      frequency of allele 90 was positively correlated with mean temperature at the
      opening of Alvinella tubes. In parallel, thermostability and thermal optimum
      experiments demonstrated that allele 90 is more thermostable and more active at
      higher temperatures than allele 100. This dataset supports an additive model of
      diversifying selection in which allele 90 is favoured on young hot chimneys but
      counterbalanced over the whole metapopulation by the dynamics of the vent
      ecosystem.

PMID- 15556888
TI  - Water turbidity by algal blooms causes mating system breakdown in a shallow-water
      fish, the sand goby Pomatoschistus minutus.
AB  - Eutrophication as a result of human activity has resulted in increased algal
      blooms and turbidity in aquatic environments. We investigated experimentally the
      effect of algal turbidity on the mating system and sexual selection in the sand
      goby, Pomatoschistus minutus (Pallas), a marine fish with a resource-defence
      mating system and paternal care. Owing to male-male competition and female
      choice, large males can monopolize multiple mates, while some males do not
      achieve mating at all. We show that the number of eggs laid was the same in both
      turbid and clear tanks but that mating success was more evenly distributed among
      males in turbid than in clear water. The opportunity for sexual selection was
      lower in turbid conditions. In turbid conditions mating success was less skewed
      towards large males. Our results suggest that increased turbidity can change
      mating systems and decrease the opportunity for sexual selection as well as
      selection intensity.

PMID- 15556889
TI  - Predation risk is an ecological constraint for helper dispersal in a
      cooperatively breeding cichlid.
AB  - Environmental conditions are thought to be responsible for the extent and
      benefits of cooperative breeding in many animal societies, but experimental tests
      are scarce. We manipulated predator pressure in the cooperatively breeding
      cichlid Neolamprologus pulcher in Lake Tanganyika, where predators have been
      suggested to influence helper and breeder survival, helper dispersal and group
      reproductive success. We varied the type and intensity of predation by releasing
      medium, large, or no predators inside large underwater cages enclosing two or
      three group territories. Helper and breeder survival, helper dispersal and group
      reproductive success decreased from the control, to the medium- and large
      predator treatments. These effects were modified by helper body size and the
      number of adults protecting the group from predators, supporting the 'group
      augmentation hypothesis'. Predators forced helpers to stay closer to, and spend
      more time inside, protective shelters. The results demonstrate the importance of
      predators for group living in this species, and support the 'ecological
      constraints hypothesis' of cooperative breeding, in the sense that subordinates
      stay at home rather than leave and breed independently under the risk of
      predation.

PMID- 15556890
TI  - Evolutionary vestigialization of sex in a clonal plant: selection versus neutral
      mutation in geographically peripheral populations.
AB  - The loss of traits that no longer contribute to fitness is widespread; however,
      the causative evolutionary mechanisms are poorly understood. Vestigialization
      could proceed through the fixation of selectively neutral degenerative mutations
      via genetic drift. Alternatively, selection may facilitate vestigialization if
      trait loss results in enhanced fitness. We tested these hypotheses using Decodon
      verticillatus, a clonal plant in which sexual sterility has arisen repeatedly in
      populations across the northern geographical range limit. We compared growth and
      survival of replicated genotypes from 7 sexually fertile and 18 sterile
      populations, over 3 years in a common environment. Survival of sterile genotypes
      was 53% greater than for fertile genotypes, but there was no difference in
      biomass accumulation. Almost all mortality, and hence increased performance of
      sterile genotypes, occurred during simulated overwinter dormancy. These
      observations suggest that selection has facilitated the vestigialization of sex,
      and thus do not support the neutral mutation hypothesis. The selective mechanism
      probably involves the relaxation of a genetic trade-off between sexual
      reproduction and survival: alleles that increase vegetative performance at the
      expense of sexual fertility are selected in geographically peripheral populations
      where sexual reproduction is suppressed by adverse environmental conditions.

PMID- 15556891
TI  - Developmental stress selectively affects the song control nucleus HVC in the
      zebra finch.
AB  - Songbirds sing complex songs as a result of evolution through sexual selection.
      The evolution of such sexually selected traits requires genetic control, as well
      as selection on their expression. Song is controlled by a discrete neural pathway
      in the brain, and song complexity has been shown to correlate with the volume of
      specific song control nuclei. As such, the development of these nuclei, in
      particular the high vocal centre (HVC), is thought to be the mechanism
      controlling signal expression indicating male quality. We tested the hypothesis
      that early developmental stress selectively affects adult HVC size, compared with
      other brain nuclei. We did this by raising cross-fostered zebra finches
      (Taeniopygia guttata) under stressed and controlled conditions and determining
      the effect on adult HVC size. Our results confirm the strong influence of
      environmental conditions, particularly on HVC development, and therefore on the
      expression of complex songs. The results also show that both environmental and
      genetic factors affect the development of several brain nuclei, highlighting the
      developmental plasticity of the songbird brain. In all, these results explain how
      the complex song repertoires of songbirds can evolve as honest indicators of male
      quality.

PMID- 15556892
TI  - Survival costs of reproduction in the blue tit (Parus caeruleus): a role for
      blood parasites?
AB  - One of the central tenets in life-history theory is that there is a trade-off
      between current and future reproduction (i.e. a cost of reproduction). The
      mechanism for this cost of reproduction is, however, largely unknown. One
      hypothesis is that the high workload during reproduction compromises resistance
      to parasites and that the resulting increase in parasitaemia has negative effects
      on the prospects of future survival. Although empirical evidence for a negative
      relationship between reproductive effort and parasite resistance exists, the
      causal relationships between reproductive effort, parasite resistance and future
      reproduction are still unclear. We use a path analytical approach to investigate
      whether a change in parasite resistance (as measured by intensities of infections
      by the blood parasite Haemoproteus) after manipulation of reproductive effort,
      translates into altered survival in female blue tits. Our results show a negative
      relationship between reproductive effort and parasite resistance, although
      evident only in first-year breeders. Moreover, we found survival costs of
      reproduction in first-year breeders. These costs were, however, not mediated by
      the blood parasite studied.

PMID- 15556893
TI  - Sexual selection and the risk of extinction in mammals.
AB  - Sexual selection is commonly envisaged as a force working in opposition to
      natural selection, because extravagant or exaggerated traits could apparently
      have never evolved via natural selection alone. There is good evidence that a
      selection load imposed by sexual selection may be eased experimentally by
      restricting the opportunity for it to operate. Sexual selection could therefore
      potentially play an important role in influencing the risk of extinction that a
      population faces, thereby contributing to the apparent selectivity of
      extinctions. Conversely, recent theory predicts that the likelihood of extinction
      may decrease when sexual selection is operating because it could accelerate the
      rate of adaptation in concert with natural selection. So far, comparative
      evidence (coming mostly from birds) has generally indicated support for the
      former scenario, but the question remains open. The aim of this study was
      therefore to examine whether the level of sexual selection (measured as residual
      testes mass and sexual size dimorphism) was related to the risk of extinction
      that mammals are currently experiencing. We found no evidence for a relationship
      between these factors, although our analyses may have been confounded by the
      possible dominating effect of contemporary anthropogenic factors.

PMID- 15556894
TI  - Partnership status and the human sex ratio at birth.
AB  - If two-parent care has different consequences for the reproductive success of
      sons and daughters, then natural selection may favour adjustment of the sex ratio
      at birth according to circumstances that forecast later family structure. In
      humans, this partnership-status hypothesis predicts fewer sons among extra-pair
      conceptions, but the rival 'attractiveness' hypothesis predicts more sons among
      extra-pair conceptions, and the 'fixed-phenotype' hypothesis predicts a constant
      probability of having a son, regardless of partnership status. In a sample of 86
      436 human births pooled from five US population-based surveys, I found 51.5% male
      births reported by respondents who were living with a spouse or partner before
      the child's conception or birth, and 49.9% male births reported by respondents
      who were not (chi(2)=16.77 d.f.=1 p<0.0001). The effect was not explained by
      paternal bias against daughters, by parental age, education, income, ethnicity or
      by year of observation, and was larger when comparisons were made between
      siblings. To my knowledge, this is the first direct evidence for conditional
      adjustment of the sex ratio at birth in humans, and could explain the recent
      decline in the sex ratio at birth in some developed countries.

PMID- 15556895
TI  - Caring for yourself with periodic health checks. Research suggests we don't need
      complete annual physicals. What now?

PMID- 15556896
TI  - A doctor talks about LDL cholesterol.

PMID- 15556897
TI  - Gastroesophageal reflux: more than just heartburn. Heartburn is the first sign of
      a gastric disorder that shouldn't be ignored.

PMID- 15556898
TI  - Sweetened drinks raise women's risk for obesity, type 2 diabetes.

PMID- 15556899
TI  - Oh, my aching neck. Your neck spends a lot of time supporting your head. No
      wonder it hurts.

PMID- 15556901
TI  - By the way, doctor. In the winter, my hands get very cold and occasionally turn
      white. Last year, even my nose got white patches. My doctor calls it a mild case
      of Raynaud's. What do you think?

PMID- 15556902
TI  - Paranoia.

PMID- 15556903
TI  - Winter depression. The treatment of seasonal affective disorder throws light on
      dark moods.

PMID- 15556904
TI  - Reality testing for insomnia.

PMID- 15556906
TI  - From subject to patient.

PMID- 15556905
TI  - The persistent popularity of benzodiazepines.

PMID- 15556907
TI  - Alzheimer's drugs: are they worth it?

PMID- 15556908
TI  - Does the new antidepressant duloxetine (Cymbalta) have any advantages over other
      antidepressant drugs?

PMID- 15556909
TI  - Medications for cholesterol: which statin is best.

PMID- 15556910
TI  - Benign prostatic hyperplasia: can herbs help?

PMID- 15556912
TI  - Diastolic heart failure--no time to relax. Trouble relaxing between beats is a
      growing cause of heart failure.

PMID- 15556911
TI  - On call: I am a 71-year-old man with diabetes and high blood pressure. Ever since
      I can remember, I've been bothered by painful canker sores two or three times a
      year. My doctor says they aren't caused by my medication and I think he's right,
      since the cankers started before I developed diabetes. What causes the sores, and
      what can I do about them?

PMID- 15556913
TI  - Swan song for antioxidant supplements. IF your take antioxidants to treat or
      prevent heart disease, it's time to rethink this gambit.

PMID- 15556914
TI  - For MERCI's sake--a new stroke treatment approved. A tiny wire curlicue that can
      snare blood clots may help more people get emergency treatment for a stroke.

PMID- 15556915
TI  - Healthy base of holiday meals. When done just right, Thanksgiving dinner can be
      good for the heart.

PMID- 15556916
TI  - Blood pressure on the rise.

PMID- 15556917
TI  - Antibiotics fail to prevent heart attacks.

PMID- 15556918
TI  - Don't bypass cardiac rehabilitation.

PMID- 15556919
TI  - Ask the doctor. Ultrasound is sometimes used to clean jewelry or break up kidney
      stones. Can the sound pressure generated by an echocardiogram damage the heart or
      cause a valve to begin leaking?

PMID- 15556920
TI  - Ask the doctor. After 10 years of successfully keeping my high blood pressure
      under control, I am now afflicted with periods of low blood pressure. Sometimes
      when I get up in the morning, it is under 100/50. What could be causing this?

PMID- 15556921
TI  - Why do we eat so much? It's simple: blame the environment!

PMID- 15556922
TI  - Choline: there's something fishy about this vitamin.

PMID- 15556923
TI  - Leeches and maggots: not appealing, might help with healing.

PMID- 15556924
TI  - Which cholesterol test should you get? The number of tests has proliferated. But
      for most people, the traditional fasting cholesterol is still the way to go.

PMID- 15556925
TI  - Bush vs. Kerry: who is healthier? Both candidates are active, so their
      cardiovascular systems seem to be in tip-top shape. But they've had health
      problems typical of men their age.

PMID- 15556926
TI  - Statins not associated with cancer.

PMID- 15556927
TI  - By the way, doctor. When I read that President Clinton learned for the first time
      in early September that he had severe heart disease, I was shocked. His health
      must have been monitored as closely as anyone's. How could something this serious
      have escaped his doctors notice? An how can someone who looked so healthy and
      vigorous as he did in July at the Democratic Convention actually be living with
      an unrecognized disease that could take his life at any moment?

PMID- 15556928
TI  - Microbial life in the Atacama Desert.

PMID- 15556929
TI  - Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are
      associated with systolic hypertension and arterial stiffness.
AB  - BACKGROUND: Arterial stiffness is an independent determinant of cardiovascular
      risk, and arterial stiffening is the predominant abnormality in systolic
      hypertension. Elastin is the main elastic component of the arterial wall and can
      be degraded by a number of enzymes, including matrix metalloproteinase-9 (MMP-9)
      and MMP-2. We hypothesized that elastase activity would be related to arterial
      stiffness and tested this using isolated systolic hypertension (ISH) as a model
      of stiffening and separately in a large cohort of healthy individuals. METHODS
      AND RESULTS: A total of 116 subjects with ISH and 114 matched controls, as well
      as 447 individuals free from cardiovascular disease were studied. Aortic and
      brachial pulse wave velocity (PWV) and augmentation index were determined. Blood
      pressure, lipids, C-reactive protein, MMP-9, MMP-2, serum elastase activity
      (SEA), and tissue-specific inhibitor 2 of metalloproteinases were measured.
      Aortic and brachial PWV, MMP-9, MMP-2, and SEA levels were increased in ISH
      subjects compared with controls (P=0.001). MMP-9 levels correlated linearly and
      significantly with aortic (r=0.45; P=0.001) and brachial PWV (r=0.22; P=0.002),
      even after adjustments for confounding variables. In the younger, healthy
      subjects, MMP-9 and SEA were also independently associated with aortic PWV.
      CONCLUSIONS: Aortic stiffness is related to MMP-9 levels and SEA, not only in
      ISH, but also in younger, apparently healthy individuals. This suggests that
      elastases including MMP-9 may be involved in the process of arterial stiffening
      and development of ISH. The relationship between arterial stiffness and elastase
      activity was examined in isolated systolic hypertension (ISH), and separately in
      a large cohort of healthy individuals. Aortic stiffness is related to MMP-9, not
      only in ISH, but also in healthy individuals, suggesting elastases may be
      involved in the process of arterial stiffening and the development of ISH.

PMID- 15556930
TI  - Characterization of structural changes in vimentin bearing an epidermolysis
      bullosa simplex-like mutation using site-directed spin labeling and electron
      paramagnetic resonance.
AB  - Mutations in intermediate filament protein genes are responsible for a number of
      inherited genetic diseases including skin blistering diseases, corneal opacities,
      and neurological degenerations. Mutation of the arginine (Arg) residue of the
      highly conserved LNDR motif has been shown to be causative in inherited disorders
      in at least four different intermediate filament (IF) proteins found in skin,
      cornea, and the central nervous system. Thus this residue appears to be broadly
      important to IF assembly and/or function. While the genetic basis for these
      diseases has been clearly defined, the inability to determine crystal structure
      for IFs has precluded a determination of how these mutations affect
      assembly/structure/function of IFs. To investigate the impact of mutation at this
      site in IFs, we have mutated the LNDR to LNDS in vimentin, a Type III
      intermediate filament protein, and have examined the impact of this change on
      assembly using electron paramagnetic resonance. Compared with wild type vimentin,
      the mutant shows normal formation of the coiled coil dimer, with a slight
      reduction in the stability of the dimer in rod domain 1. Probing the dimer-dimer
      interactions shows the formation of normal dimer centered on residue 191 but a
      failure of dimerization at residue 348 in rod domain 2. These data point toward a
      specific stage of assembly at which a common disease-causing mutation in IF
      proteins interrupts assembly.

PMID- 15556931
TI  - Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in
      Drosophila.
AB  - Parkinson's disease is a common neurodegenerative disease characterized by the
      loss of dopaminergic neurons in the substantia nigra pars compacta and the
      accumulation of the protein alpha-synuclein into aggregates called Lewy bodies
      and Lewy neurites. Parkinson's disease can be modeled in Drosophila where
      directed expression of alpha-synuclein induces compromise of dopaminergic neurons
      and the formation of Lewy body-like aggregates. The molecular chaperone Hsp70
      protects cells from the deleterious effects of alpha-synuclein, indicating a
      potential therapeutic approach to enhance neuron survival in Parkinson's disease.
      We have now investigated the molecular mechanisms by which the drug geldanamycin
      protects neurons against alpha-synuclein toxicity. Our studies show that
      geldanamycin sensitizes the stress response within normal physiological
      parameters to enhance chaperone activation, offering protection against alpha
      synuclein neurotoxicity. Further, geldanamycin uncouples neuronal toxicity from
      Lewy body and Lewy neurite formation such that dopaminergic neurons are protected
      from the effects of alpha-synuclein expression despite the continued presence of
      (and even increase in) inclusion pathology. These studies indicate that compounds
      that modulate the stress response are a promising approach to treat Parkinson's
      disease.

PMID- 15556932
TI  - Induced fit of an epitope peptide to a monoclonal antibody probed with a novel
      parallel surface plasmon resonance assay.
AB  - Class II major histocompatibility complex proteins bind peptides for presentation
      to T-cells as part of the immune response process. Monoclonal antibody MEM-265
      recognizes the peptide-free conformation of the major histocompatibility complex
      class II protein HLA-DR1 through specific binding to an epitope contained between
      residues 50-67 of the beta-chain. In previous work using alanine scanning (1), we
      identified residues Leu-53, Asp-57, Tyr-60, Trp-61, Ser-63, and Leu-67 as
      essential for specific recognition by MEM-265. The spacing of these residues
      approximates a 3.5-residue repeat, suggesting that MEM-265 may recognize the
      epitope in an alpha-helical conformation. In the folded, peptide-loaded DR1
      structure, the beta-chain residues 50-67 contain a kinked alpha-helical segment
      spanning Glu-52-Ser-63 (2). However, the conformation of this segment in the
      peptide-free form is unknown. We have used a new surface plasmon resonance
      approach in a SpotMatrix format to compare the kinetic rates and affinities for
      18 alanine scanning mutants comprising epitope residues 50-67. In addition to the
      six essential residues described previously, we found two additional residues,
      Glu-52 and Gln-64, that contribute by enhancing MEM-265 binding. By contrast,
      mutation of either Gly-54 or Pro-56 to an alanine actually improved binding to
      MEM-265. In essentially all cases peptide substitutions that either improve or
      reduce MEM-265 recognition could be traced to differences in the dissociation
      rate (k off). The kinetic details of the present study support the presence of a
      structural component in the antigenic epitope recognized by MEM-265 in the
      peptide-free form of major histocompatibility complex II DR1 beta-chain.

PMID- 15556933
TI  - A stable tyrosyl radical in monoamine oxidase A.
AB  - We present spectroscopic evidence consistent with the presence of a stable
      tyrosyl radical in partially reduced human monoamine oxidase (MAO) A. The radical
      forms following single electron donation to MAO A and exists in equilibrium with
      the FAD flavosemiquinone. Oxidative formation of the tyrosyl radical in MAO is
      not reliant on neighboring metal centers and uniquely requires reduction of the
      active site flavin to facilitate oxidation of a tyrosyl side chain. The
      identified tyrosyl radical provides the key missing link in support of the single
      electron transfer mechanism for amine oxidation by MAO enzymes.

PMID- 15556934
TI  - Recruitment of phosphoinositide 3-kinase defines a positive contribution of
      tyrosine kinase signaling to E-cadherin function.
AB  - Classical cadherin adhesion molecules can function as adhesion-activated cell
      signaling receptors. One key target for cadherin signaling is the lipid kinase
      phosphoinositide (PI) 3-kinase, which is recruited to cell-cell contacts and
      activated by E-cadherin. In this study, we sought to identify upstream factors
      necessary for E-cadherin to activate PI 3-kinase signaling. We found that
      inhibition of tyrosine kinase signaling blocked recruitment of PI 3-kinase to E
      cadherin contacts and abolished the ability of E-cadherin to activate PI 3-kinase
      signaling. Tyrosine kinase inhibitors further perturbed several parameters of
      cadherin function, including cell adhesion and the ability of cells to
      productively extend nascent cadherin-adhesive contacts. Notably, the functional
      effects of tyrosine kinase blockade were rescued by expression of a
      constitutively active form of PI 3-kinase that restores PI 3-kinase signaling.
      Finally, using dominant negative Src mutants and Src-null cells, we identified
      Src as one key upstream kinase in the E-cadherin/PI 3-kinase-signaling pathway.
      Taken together, our findings indicate that tyrosine kinase activity, notably Src
      signaling, can contribute positively to cadherin function by supporting E
      cadherin signaling to PI 3-kinase.

PMID- 15556935
TI  - Yeast-like mRNA capping apparatus in Giardia lamblia.
AB  - A scheme of eukaryotic phylogeny has been suggested based on the structure and
      physical linkage of the RNA triphosphatase and RNA guanylyltransferase enzymes
      that catalyze mRNA cap formation. Here we show that the unicellular pathogen
      Giardia lamblia encodes an mRNA capping apparatus consisting of separate
      triphosphatase and guanylyltransferase components, which we characterize
      biochemically. We also show that native Giardia mRNAs have blocked 5'-ends and
      that 7-methylguanosine caps promote translation of transfected mRNAs in Giardia
      in vivo. The Giardia triphosphatase belongs to the tunnel family of metal
      dependent phosphohydrolases that includes the RNA triphosphatases of fungi,
      microsporidia, and protozoa such as Plasmodium and Trypanosoma. The tunnel
      enzymes adopt a unique active-site fold and are structurally and mechanistically
      unrelated to the cysteine-phosphatase-type RNA triphosphatases found in metazoans
      and plants, which comprise part of a bifunctional
      triphosphataseguanylyltransferase fusion protein. All available evidence now
      points to the separate tunnel-type triphosphatase and guanylyltransferase as the
      aboriginal state of the capping apparatus. We identify a putative tunnel-type
      triphosphatase and a separate guanylyltransferase encoded by the red alga
      Cyanidioschyzon merolae. These findings place fungi, protozoa, and red algae in a
      common lineage distinct from that of metazoa and plants.

PMID- 15556936
TI  - Dimeric galectin-1 binds with high affinity to alpha2,3-sialylated and non
      sialylated terminal N-acetyllactosamine units on surface-bound extended glycans.
AB  - Galectin-1 is a member of the galectin family of glycan-binding proteins and
      occurs as an approximately 29.5-kDa noncovalent homodimer (dGal-1) that is widely
      expressed in many tissues. Here, we report that human recombinant dGal-1 bound
      preferentially and with high affinity (apparent K(d) approximately 2-4 microM) to
      immobilized extended glycans containing terminal N-acetyllactosamine (LN;
      Galbeta1-4GlcNAc) sequences on poly-N-acetyllactosamine (PL; (-3Galbeta1
      4GlcNAcbeta1-)(n)) sequences, complex-type biantennary N-glycans, or novel chitin
      derived glycans modified to contain terminal LN. Although terminal Gal residues
      are important for dGal-1 recognition, dGal-1 bound similarly to alpha3-sialylated
      and alpha2-fucosylated terminal LN, but not to alpha6-sialylated and alpha3
      fucosylated terminal LN. The binding specificity of human recombinant dGal-1 was
      similar to that observed with purified bovine heart-derived dGal-1. Unexpectedly,
      dGal-1 bound free ligands in solution with relatively low affinity and displayed
      no preference for extended glycans, indicating that dGal-1 preferentially
      recognizes extended glycans only when they are surface-bound, such as found on
      cell surfaces. Human dGal-1 also bound to both native and desialylated human
      promyelocytic HL-60 cells with similar affinity as observed for immobilized long
      chain PL. Binding to these cells was reduced upon treatment with endo-beta
      galactosidase, which cleaves PL sequences, indicating that cell-surface PLs are
      ligands. To test the role of dimerization in dGal-1 binding, we examined the
      binding of a mutated form of dGal-1 that weakly dimerizes (monomeric Gal-1 (mGal
      1)) and a covalently dimerized (chemically cross-linked) form of mGal-1 (cd-mGal
      1). dGal-1 and cd-mGal-1 had similar affinities that were both approximately 3.5
      fold higher for immobilized PL than observed for mGal-1, suggesting that dGal-1
      acts as a dimer to cross-link terminal LN units on immobilized PL. These results
      indicate that dGal-1 functions as a dimer to recognize LN units on extended PLs
      on cell surfaces.

PMID- 15556937
TI  - Chromatin-dependent E1A activity modulates NF-kappaB RelA-mediated repression of
      glucocorticoid receptor-dependent transcription.
AB  - The role of chromatin-dependent regulatory mechanisms in the repression of
      glucocorticoid-dependent transcription from the murine mammary tumor virus (MMTV)
      promoter by p65 and E1A was investigated by using chromatin and transiently
      transfected reporters. The p65 RelA subunit of NF-kappaB represses MMTV
      expression on either transient or integrated reporters. In contrast, the viral
      oncoprotein E1A represses a transient but not an integrated MMTV. E1A repression
      is attenuated by chromatin, suggesting p65 but not E1A manipulates chromatin
      appropriately to inhibit the GR. Coexpression of p65 and E1A additively represses
      the transient MMTV but restores the transcriptional activation of the chromatin
      MMTV in response to glucocorticoids. This indicates that E1A has a dominant
      chromatin-dependent activity that attenuates repression by p65. E1A, p65, and GR
      bind the MMTV promoter, and chromatin remodeling enhances binding on both
      repressed and activated promoters. In addition, p65 requires Brg for repression
      of the integrated MMTV. This suggests that neither p65 repression nor E1A
      attenuation of repression results from an inhibition of remodeling that prevents
      transcription factor binding. Furthermore, p300/CBP is also required for both
      repression and attenuation by p65 and E1A. E1A and p65 mutants that do not bind
      p300/CBP are inactive, indicative of a requirement for p300/CBP-dependent complex
      formation for both repression and attenuation with chromatin. These data suggest
      that both the p65-dependent repression and the E1A-mediated attenuation of
      repression require the Brg1-dependent chromatin remodeling function and p300/CBP
      dependent complex formation at a promoter assembled within chromatin.

PMID- 15556938
TI  - Identification of FGF10 targets in the embryonic lung epithelium during bud
      morphogenesis.
AB  - Genetic studies implicate Fgf10-Fgfr2 signaling as a critical regulator of bud
      morphogenesis in the embryo. However, little is known about the transcriptional
      targets of Fgf10 during this process. Here we identified global changes in gene
      expression in lung epithelial explants undergoing FGF10-mediated budding in the
      absence of other growth factors and mesenchyme. Targets were confirmed by their
      localization at sites where endogenous Fgf10 signaling is active in embryonic
      lungs and by demonstrating their induction in intact lungs in response to local
      application of FGF10 protein. We show that the initial stages of budding are
      characterized by marked up-regulation of genes associated with cell rearrangement
      and cell migration, inflammatory process, and lipid metabolism but not cell
      proliferation. We also found that some genes implicated in tumor invasion and
      metastatic behavior are epithelial targets of Fgf10 in the lung and other
      developing organs that depend on Fgf10-Fgfr2 signaling to properly form. Our
      approach identifies Fgf10 targets that are common to multiple biological
      processes and provides insights into potential mechanisms by which Fgf signaling
      regulates epithelial cell behavior.

PMID- 15556939
TI  - Ribophorin I associates with a subset of membrane proteins after their
      integration at the sec61 translocon.
AB  - The biosynthesis of membrane proteins at the endoplasmic reticulum (ER) involves
      the integration of the polypeptide at the Sec61 translocon together with a number
      of maturation events, such as N-glycosylation and signal sequence cleavage, that
      can occur both during and after synthesis. To better understand the events
      occurring after the release of the nascent chain from the ER translocon, we
      investigated the ER components adjacent to the transmembrane-spanning domain of a
      well characterized fragment of the amyloid precursor protein. Using individual
      cysteine residues as site-specific cross-linking targets, we found that several
      ER components can be cross-linked to the fully integrated polypeptide. We
      identified strong adducts with both the ribophorin I subunit of the
      oligosaccharyltransferase complex and the 25-kDa subunit of the signal peptidase
      complex. Focusing on the association with ribophorin I, we found that adduct
      formation occurred exclusively after the exit of the nascent chain from the Sec61
      translocon and was unaffected by the N-glycosylation status of the associated
      precursor. Only a subset of newly made membrane proteins associated with
      ribophorin I in vitro, and we could recapitulate a specific association between
      the amyloid precursor protein fragment and ribophorin I in vivo. Taken together,
      our data suggest a model where ribophorin I may function to retain potential
      substrates in close proximity to the catalytic subunit of the
      oligosaccharyltransferase and thereby stochastically improve the efficiency of
      the N-glycosylation reaction in vivo. Alternatively ribophorin I may be
      multifunctional and facilitate additional processes, for example, ER quality
      control.

PMID- 15556940
TI  - Altered oxyanion selectivity in mutants of UhpT, the Pi-linked sugar phosphate
      carrier of Escherichia coli.
AB  - In Escherichia coli, the UhpT transporter catalyzes the electroneutral
      accumulation of sugar 6-phosphate by exchange with internal inorganic phosphate
      (Pi). The substrate specificity of UhpT is regulated at least in part by
      constituents of an Asp388-Lys391 intrahelical salt bridge, and mutations that
      remove one but not both of these residues alter UhpT preference for
      organophosphate substrates. Using site-directed mutagenesis, we examined the role
      played by these two positions in the selection of the oxyanion countersubstrate.
      We show that derivatives having aliphatic or polar residues at positions 388 and
      391 are gain-of-function mutants capable of transporting SO4 as well as Pi. These
      oxyanions share similar structures but differ significantly in the presence of a
      proton(s) on Pi. Our findings therefore lead us to suggest that the Asp388-Lys391
      ion pair acts normally as a filter that prevents substrates lacking a proton that
      can be donated from occupying the UhpT active site.

PMID- 15556941
TI  - Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell
      death via mitochondrial hyperpolarization, budding, and fission.
AB  - Galectins have emerged as a novel family of immunoregulatory proteins implicated
      in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key
      role in tumor-immune escape by killing antitumor effector T cells. Here we found
      that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell
      death. Furthermore, this protein triggers an apoptotic program involving an
      increase of mitochondrial membrane potential and participation of the ceramide
      pathway. In addition, Gal-1 induces mitochondrial coalescence, budding, and
      fission accompanied by an increase and/or redistribution of fission-associated
      molecules h-Fis and DRP-1. Importantly, these changes are detected in both
      resting and activated human T cells, suggesting that Gal-1-induced cell death
      might become an excellent model to analyze the morphogenetic changes of
      mitochondria during the execution of cell death. This is the first association
      among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway,
      providing a rational basis for the immunoregulatory properties of Gal-1 in
      experimental models of chronic inflammation and cancer.

PMID- 15556942
TI  - Activation of CD38 by interleukin-8 signaling regulates intracellular Ca2+ level
      and motility of lymphokine-activated killer cells.
AB  - CD38 is an ADP-ribosyl cyclase, producing a potent Ca(2+) mobilizer cyclic ADP
      ribose (cADPR). In this study, we have investigated a role of CD38 and its
      regulation through interleukin-8 (IL8) signaling in lymphokine-activated killer
      (LAK) cells. Incubation of LAK cells with IL8 resulted in an increase of cellular
      cADPR level and a rapid rise of intracellular Ca(2+) concentration ([Ca(2+)](i)),
      which was sustained for a long period of time (>10 min). Preincubation of an
      antagonistic cADPR analog, 8-Br-cADPR (8-bromo-cyclic adenosine diphosphate
      ribose), abolished the sustained Ca(2+) signal only but not the initial Ca(2+)
      rise. An inositol 1,4,5-trisphosphate (IP(3)) receptor antagonist blocked both
      Ca(2+) signals. Interestingly, the sustained Ca(2+) rise was not observed in the
      absence of extracellular Ca(2+). Functional CD38-null (CD38(-)) LAK cells showed
      the initial rapid increase of [Ca(2+)](i) but not the sustained Ca(2+) rise in
      response to IL8 treatment. An increase of cellular cADPR level by cGMP analog, 8
      pCPT-cGMP (8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate), but not
      cAMP analog or phorbol 12-myristate 13-acetate was observed. IL8 treatment
      resulted in the increase of cGMP level that was inhibited by the IP(3) receptor
      blocker but not a protein kinase C inhibitor. cGMP-mediated Ca(2+) rise was
      blocked by 8-Br-cADPR. In addition, IL8-mediated LAK cell migration was inhibited
      by 8-Br-cADPR and a protein kinase G inhibitor. Consistent with these
      observations, IL8-induced migration of CD38(-) LAK cells was not observed.
      However, direct application of cADPR or 8-pCPT-cGMP stimulated migration of CD38(
      ) cells. These results demonstrate that CD38 is stimulated by sequential
      activation of IL8 receptor, IP(3)-mediated Ca(2+) rise, and cGMP/protein kinase G
      and that CD38 plays an essential role in IL8-induced migration of LAK cells.

PMID- 15556943
TI  - The role of RuvA octamerization for RuvAB function in vitro and in vivo.
AB  - RuvA plays an essential role in branch migration of the Holliday junction by
      RuvAB as part of the RuvABC pathway for processing Holliday junctions in
      Escherichia coli. Two types of RuvA-Holliday junction complexes have been
      characterized: 1) complex I containing a single RuvA tetramer and 2) complex II
      in which the junction is sandwiched between two RuvA tetramers. The functional
      differences between the two forms are still not clear. To investigate the role of
      RuvA octamerization, we introduced three amino acid substitutions designed to
      disrupt the E. coli RuvA tetramer-tetramer interface as identified by structural
      studies. The mutant RuvA was tetrameric and interacted with both RuvB and
      junction DNA but, as predicted, formed complex I only at protein concentrations
      up to 500 nm. We present biochemical and surface plasmon resonance evidence for
      functional and physical interactions of the mutant RuvA with RuvB and RuvC on
      synthetic junctions. The mutant RuvA with RuvB showed DNA helicase activity and
      could support branch migration of synthetic four-way and three-way junctions.
      However, junction binding and the efficiency of branch migration of four-way
      junctions were affected. The activity of the RuvA mutant was consistent with a
      RuvAB complex driven by one RuvB hexamer only and lead us to propose that one
      RuvA tetramer can only support the activity of one RuvB hexamer. Significantly,
      the mutant failed to complement the UV sensitivity of E. coli DeltaruvA cells.
      These results indicate strongly that RuvA octamerization is essential for the
      full biological activity of RuvABC.

PMID- 15556944
TI  - Gene 33 is an endogenous inhibitor of epidermal growth factor (EGF) receptor
      signaling and mediates dexamethasone-induced suppression of EGF function.
AB  - We report a mechanism by which the adapter protein Gene 33 (also called RALT and
      MIG6) regulates epidermal growth factor receptor (EGFR) signaling. We find that
      Gene 33 inhibits EGFR autophosphorylation and specifically blunts epidermal
      growth factor (EGF)-induced activation and/or phosphorylation of Ras, ERK, JNK,
      Akt/PKB, and retinoblastoma protein. The Ack homology domain of Gene 33, which
      contains the previously identified EGFR binding domain, is both necessary and
      sufficient for this inhibition of EGFR autophosphorylation. The endogenous Gene
      33 polypeptide is induced by EGF, platelet-derived growth factor, serum, and
      dexamethasone (Dex) in Rat 2 rat fibroblasts. Dex induces Gene 33 expression and
      inhibits EGFR phosphorylation and EGF signaling. RNA interference-mediated
      silencing of Gene 33 significantly reverses this effect. Overexpression of Gene
      33 completely blocks EGF-induced protein and DNA synthesis in Rat 2 cells,
      whereas gene 33 RNA interference substantially enhances EGF-induced protein and
      DNA synthesis in Rat 2 cells. Our results indicate that Gene 33 is a
      physiological feedback inhibitor of the EGFR, functioning to inhibit EGFR
      phosphorylation and all events induced by EGFR activation. Our results also
      indicate a role for Gene 33 in the suppression, by Dex, of EGF signaling
      pathways. We propose that Gene 33 may function in the cross-talk between EGF
      signaling and other mitogenic and/or stress signaling pathways.

PMID- 15556945
TI  - Expression of class A scavenger receptor is enhanced by high glucose in vitro and
      under diabetic conditions in vivo: one mechanism for an increased rate of
      atherosclerosis in diabetes.
AB  - In the early stage of atherosclerosis, macrophages take up chemically modified
      low density lipoproteins (LDL) through the scavenger receptors, leading to foam
      cell formation in atherosclerotic lesions. To get insight into a role of the
      scavenger receptors in diabetes-enhanced atherosclerotic complications, the
      effects on class A scavenger receptor (SR-A) of high glucose exposure in vitro as
      well as the diabetic conditions in vivo were determined in the present study. The
      in vitro experiments demonstrated that high glucose exposure to human monocyte
      derived macrophages led to an increased SR-A expression with a concomitant
      increase in the endocytic uptake of acetylated LDL and oxidized LDL. The
      endocytic process was significantly suppressed by an anti-SR-A neutralizing
      antibody. Stability analyses revealed a significant increased stability of SR-A
      at a mRNA level but not a protein level, indicating that high glucose-induced up
      regulation of SR-A is due largely to increased stability of SR-A mRNA. High
      glucose-enhanced SR-A expression was prevented by protein kinase C and NAD(P)H
      oxidase inhibitors as well as antioxidants. High glucose-enhanced production of
      intracellular peroxides was visualized in these cells, which was attenuated by an
      antioxidant. The in vivo experiments demonstrated that peritoneal macrophages
      from streptozotocin-induced diabetic mice increased SR-A expression when compared
      with those from nondiabetic mice. Endocytic degradation of acetylated LDL and
      oxidized LDL were also increased with these macrophages but not with the
      corresponding macrophages from diabetic SR-A knock-out mice. These in vitro and
      in vivo results probably suggest that reactive oxygen species generated from a
      protein kinase C-dependent NAD(P)H oxidase pathway plays a role in the high
      glucose-induced up-regulation of SR-A, leading to the increased endocytic
      degradation of modified LDL for foam cell formation. This could be one mechanism
      for an increased rate of atherosclerosis in patients with diabetes.

PMID- 15556946
TI  - A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5
      subcellular localization.
AB  - Interferon regulatory factors (IRFs) are involved in gene regulation in many
      biological processes including the antiviral, growth regulatory, and immune
      modulatory functions of the interferon system. Several studies have demonstrated
      that IRF-3, IRF-5, and IRF-7 specifically contribute to the innate antiviral
      response to virus infection. It has been reported that virus-specific
      phosphorylation leads to IRF-5 nuclear localization and up-regulation of
      interferon, cytokine, and chemokine gene expression. Two nuclear localization
      signals have been identified in IRF-5, both of which are sufficient for nuclear
      translocation and retention in virus-infected cells. In the present study, we
      demonstrate that a CRM1-dependent nuclear export pathway is involved in the
      regulation of IRF-5 subcellular localization. IRF-5 possesses a functional
      nuclear export signal (NES) that controls dynamic shuttling between the cytoplasm
      and the nucleus. The NES element is dominant in unstimulated cells and results in
      the predominant cytoplasmic localization of IRF-5. Mutation of two leucine
      residues in the NES motif to alanine, or three adjacent Ser/Thr residues to the
      phosphomimetic Asp, results in constitutively nuclear IRF-5 and suggests that
      phosphorylation of adjacent Ser/Thr residues may contribute to IRF-5 nuclear
      accumulation in virus-induced cells. IKK-related kinases TBK1 and IKKepsilon have
      been shown to phosphorylate and activate IRF-3 and IRF-7, leading to the
      production of type 1 interferons and the development of a cellular antiviral
      state. We examined the phosphorylation and activation of IRF-5 by TBK1 and
      IKKepsilon kinases. Although IRF-5 is phosphorylated by IKKepsilon and TBK1 in co
      transfected cells, the phosphorylation of IRF-5 did not lead to IRF-5 nuclear
      localization or activation.

PMID- 15556947
TI  - ADAR1 RNA deaminase limits short interfering RNA efficacy in mammalian cells.
AB  - Double-stranded RNA induces the homology-dependent degradation of cognate mRNA in
      the cytoplasm via RNA interference (RNAi) but also is a target for adenosine-to
      inosine (A-to-I) RNA editing by adenosine deaminases acting on RNA (ADARs). An
      interaction between the RNAi and the RNA editing pathways in Caenorhabditis
      elegans has been suggested recently, but the precise mode of interaction remains
      to be established. In addition, it is unclear whether this interaction is
      possible in mammalian cells with their somewhat different RNAi pathways. Here we
      show that ADAR1 and ADAR2, but not ADAR3, avidly bind short interfering RNA
      (siRNA) without RNA editing. In particular, the cytoplasmic full-length isoform
      of ADAR1 has the highest affinity among known ADARs, with a subnanomolar
      dissociation constant. Gene silencing by siRNA is significantly more effective in
      mouse fibroblasts homozygous for an ADAR1 null mutation than in wild-type cells.
      In addition, suppression of RNAi effects are detected in fibroblast cells
      overexpressing functional ADAR1 but not when overexpressing mutant ADAR1 lacking
      double-stranded RNA-binding domains. These results identify ADAR1 as a cellular
      factor that limits the efficacy of siRNA in mammalian cells.

PMID- 15556948
TI  - Phosphorylation by MAPK regulates simian immunodeficiency virus Vpx protein
      nuclear import and virus infectivity.
AB  - Transport of the viral genome into the nucleus required phosphorylation of
      components in the preintegration complex by virion-associated host cellular
      kinases. In this study, we showed that ERK-2/MAPK is associated with simian
      immunodeficiency virus (SIV) virions and regulated the nuclear transport of Vpx
      and virus replication in non-proliferating target cells by phosphorylating Vpx.
      Suppression of the virion-associated ERK-2 activity by MAPK pathway inhibitors
      impaired both Vpx nuclear import and viral infectivity without affecting virus
      particle maturation and release. In addition, mutation analysis indicated that
      the inactivation of Vpx phosphorylation precluded nuclear import and reduced
      virus replication in macrophage cultures, even when functional integrase and Gag
      matrix proteins implicated in viral preintegration complex nuclear import are
      present. In this study, we also showed that co-localization of Vpx with Gag
      precursor in the cytoplasm is a prerequisite for Vpx incorporation into virus
      particles. Substitution of hydrophobic Leu-74 and Ile-75 with serines in the
      helical domain abrogated Vpx nuclear import, and its incorporation into virus
      particles, despite its localization in the cytoplasm, suggested that the
      structural integrity of helical domains is critical for Vpx functions. Taken
      together, these studies demonstrated that the host cell MAPK signal transduction
      pathway regulated an early step in SIV infection.

PMID- 15556949
TI  - Contribution of transmembrane regions to ATP-gated P2X2 channel permeability
      dynamics.
AB  - ATP-gated P2X(2) channels undergo activation-dependent permeability increases as
      they proceed from the selective I(1) state to the I(2) state that is readily
      permeable to organic cations. There are two main models about how permeability
      changes may occur. The first proposes that permeability change-competent P2X
      channels are clustered or redistribute to form such regions in response to ATP.
      The second proposes that permeability changes occur because of an intrinsic
      conformational change in P2X channels. In the present study we experimentally
      tested these views with total internal reflection fluorescence microscopy,
      electrophysiology, and mutational perturbation analysis. We found no evidence for
      clusters of P2X(2) channels within the plasma membrane or for cluster formation
      in response to ATP, suggesting that channel clustering is not an obligatory
      requirement for permeability changes. We next sought to identify determinants of
      putative intrinsic conformational changes in P2X(2) channels by mapping the
      transmembrane domain regions involved in the transition from the relatively
      selective I(1) state to the dilated I(2) state. Initial channel opening to the
      I(1) state was only weakly affected by Ala substitutions, whereas dramatic
      effects were observed for the higher permeability I(2) state. Ten residues
      appeared to perturb only the I(1)-I(2) transition (Phe(31), Arg(34), Gln(37),
      Lys(53), Ile(328), Ile(332), Ser(340), Gly(342), Trp(350), Leu(352)). The data
      favor the hypothesis that permeability changes occur because of permissive
      motions at the interface between first and second transmembrane domains of
      neighboring subunits in pre-existing P2X(2) channels.

PMID- 15556950
TI  - Characterization of peptides released from mitochondria: evidence for constant
      proteolysis and peptide efflux.
AB  - Conserved ATP-dependent proteases ensure the quality control of mitochondrial
      proteins and control essential steps in mitochondrial biogenesis. Recent studies
      demonstrated that non-assembled mitochondrially encoded proteins are degraded to
      peptides and amino acids that are released from mitochondria. Here, we have
      characterized peptides extruded from mitochondria by mass spectrometry and
      identified 270 peptides that are exported in an ATP- and temperature-dependent
      manner. The peptides originate from 51 mitochondrially and nuclearly encoded
      proteins localized mainly in the matrix and inner membrane, indicating that
      peptides generated by the activity of all known mitochondrial ATP-dependent
      proteases can be released from the organelle. Pulse-labeling experiments in
      logarithmically growing yeast cells revealed that approximately 6-12% of
      preexisting and newly imported proteins is degraded and contribute to this
      peptide pool. Under respiring conditions, we observed an increased proteolysis of
      newly imported proteins that suggests a higher turnover rate of respiratory chain
      components and thereby rationalizes the predominant appearance of representatives
      of this functional class in the detected peptide pool. These results demonstrated
      a constant efflux of peptides from mitochondria and provided new insight into the
      stability of the mitochondrial proteome and the efficiency of mitochondrial
      biogenesis.

PMID- 15556953
TI  - Rise in "no indicated risk" primary caesareans in the United States, 1991-2001:
      cross sectional analysis.

PMID- 15556954
TI  - United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial:
      cost effectiveness of physical treatments for back pain in primary care.
AB  - OBJECTIVE: To assess the cost effectiveness of adding spinal manipulation,
      exercise classes, or manipulation followed by exercise ("combined treatment") to
      "best care" in general practice for patients consulting with low back pain.
      DESIGN: Stochastic cost utility analysis alongside pragmatic randomised trial
      with factorial design. SETTING: 181 general practices and 63 community settings
      for physical treatments around 14 centres across the United Kingdom.
      PARTICIPANTS: 1287 (96%) of 1334 trial participants. MAIN OUTCOME MEASURES:
      Healthcare costs, quality adjusted life years (QALYs), and cost per QALY over 12
      months. RESULTS: Over one year, mean treatment costs relative to "best care" were
      195 pounds sterling (360 dollars; 279 euros; 95% credibility interval 85 pounds
      sterling to 308 pounds sterling) for manipulation, 140 pounds sterling (3 pounds
      sterling to 278 pounds sterling) for exercise, and 125 pounds sterling (21 pounds
      sterling to 228 pounds sterling) for combined treatment. All three active
      treatments increased participants' average QALYs compared with best care alone.
      Each extra QALY that combined treatment yielded relative to best care cost 3800
      pounds sterling; in economic terms it had an "incremental cost effectiveness
      ratio" of 3800 pounds sterling. Manipulation alone had a ratio of 8700 pounds
      sterling relative to combined treatment. If the NHS was prepared to pay at least
      10,000 pounds sterling for each extra QALY (lower than previous recommendations
      in the United Kingdom), manipulation alone would probably be the best strategy.
      If manipulation was not available, exercise would have an incremental cost
      effectiveness ratio of 8300 pounds sterling relative to best care. CONCLUSIONS:
      Spinal manipulation is a cost effective addition to "best care" for back pain in
      general practice. Manipulation alone probably gives better value for money than
      manipulation followed by exercise.

PMID- 15556955
TI  - United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial:
      effectiveness of physical treatments for back pain in primary care.
AB  - OBJECTIVE: To estimate the effect of adding exercise classes, spinal manipulation
      delivered in NHS or private premises, or manipulation followed by exercise to
      "best care" in general practice for patients consulting with back pain. [See
      figure]. DESIGN: Pragmatic randomised trial with factorial design. SETTING: 181
      general practices in Medical Research Council General Practice Research
      Framework; 63 community settings around 14 centres across the United Kingdom.
      PARTICIPANTS: 1334 patients consulting their general practices about low back
      pain. MAIN OUTCOME MEASURES: Scores on the Roland Morris disability questionnaire
      at three and 12 months, adjusted for centre and baseline scores. RESULTS: All
      groups improved over time. Exercise improved mean disability questionnaire scores
      at three months by 1.4 (95% confidence interval 0.6 to 2.1) more than "best
      care." For manipulation the additional improvement was 1.6 (0.8 to 2.3) at three
      months and 1.0 (0.2 to 1.8) at 12 months. For manipulation followed by exercise
      the additional improvement was 1.9 (1.2 to 2.6) at three months and 1.3 (0.5 to
      2.1) at 12 months. No significant differences in outcome occurred between
      manipulation in NHS premises and in private premises. No serious adverse events
      occurred. CONCLUSIONS: Relative to "best care" in general practice, manipulation
      followed by exercise achieved a moderate benefit at three months and a small
      benefit at 12 months; spinal manipulation achieved a small to moderate benefit at
      three months and a small benefit at 12 months; and exercise achieved a small
      benefit at three months but not 12 months.

PMID- 15556956
TI  - A perspective on the research literature related to early intensive behavioral
      intervention (Lovaas) for young children with autism.
AB  - Various aspects of the research literature on early intensive behavioral
      intervention (EIBI) have been poorly understood within the psychological,
      educational, and advocacy communities. Examination of the studies that are
      frequently cited by proponents of EIBI suggests that the expectation that 47
      percent of youngsters who receive EIBI will reach normal developmental status is
      questionable.

PMID- 15556957
TI  - Social skills assessment of children with autism in free-play situations.
AB  - Poor social functioning and limited play are characteristic of children with
      autism. Increasingly, education for children with autism is provided within
      mainstream settings, but given their particular difficulties, the adequate
      provision of educational services in such settings is challenging. This study
      presents observational data of the play behaviour and social interaction patterns
      of 10 children with autism in mainstream kindergartens and primary school
      playgrounds. The target children differed significantly in terms of their play
      and social interactions from typically developing children in the same settings.
      The adequacy of the provision of services for children with autism in mainstream
      provision is discussed.

PMID- 15556958
TI  - A survey of parents' reactions to the diagnosis of an autistic spectrum disorder
      by a local service: access to information and use of services.
AB  - We conducted a postal survey of parents whose child had been diagnosed with an
      autistic spectrum disorder by a district diagnostic service. The service was
      regarded as having improved significantly following recent changes, but there
      were still shortcomings. Parents had obtained useful information from a range of
      other sources, including a parents' support group, school teachers, speech and
      language therapists, educational psychologists, the Internet, books and academic
      journals. Special units and schools were rated as the most useful source of
      support and treatment, but many other interventions were rated highly. Parents
      reported a diverse range of both negative and positive consequences of diagnosis,
      and many reported a change in their attitudes to diagnosis over time. Many
      expressed frustration with trying to get an early diagnosis, with the social,
      educational and health services, and with the way that autistic spectrum
      disorders are regarded by lay people and other parents.

PMID- 15556959
TI  - Mothers supporting children with autistic spectrum disorders: social support,
      mental health status and satisfaction with services.
AB  - Parents of children with autistic spectrum disorders (ASDs) are more likely to
      experience serious psychological distress than parents of children with other
      developmental disabilities. To examine the impact of a range of factors on
      psychological wellbeing, interviews were undertaken with 68 mothers of children
      with ASDs to explore aspects of social support, mental health status and
      satisfaction with services. Findings indicated that over half of mothers screened
      positive for significant psychological distress and that this was associated with
      low levels of family support and with bringing up a child with higher levels of
      challenging behaviour. Mothers were more likely to report lower levels of support
      if they were a lone parent, were living in poor housing, or were the mother of a
      boy with ASD. The study also investigated areas of useful support and areas of
      unmet need, the latter including care breaks and advice needs.

PMID- 15556960
TI  - The health and social care needs of family carers supporting adults with autistic
      spectrum disorders.
AB  - The families of 26 adults with autistic spectrum disorders (ASDs) who either
      lived at home or maintained close contact with their families were interviewed
      about their social and psychological needs related to caring for the person with
      ASD. In contrast to previous studies of familial carers of children with ASDs, a
      strong association between parental emotional distress and unmet need was found.
      Parents also reported a need for more autism-specific intervention and support
      for adults with ASDs. The study illustrates the continuing and underreported role
      of families in supporting adults with ASDs.

PMID- 15556961
TI  - Rationale for further investigation of chromosome 16p13.3, a region implicated
      for autism.

PMID- 15556964
TI  - Is the clinical efficacy of epidural diamorphine concentration-dependent when
      used as analgesia for labour?
AB  - BACKGROUND: The physicochemical properties of diamorphine (3,6-diacetylmorphine)
      enhance its bioavailability compared with more lipid-soluble opioids when
      administered into the epidural space. However, the influence of concentration,
      volume or mass on the clinical efficacy of diamorphine is not known. METHOD: In
      this double-blind, randomized, prospective study, 62 women in active labour and
      </=5 cm cervical dilatation were recruited to determine whether the mode of
      action of diamorphine in the epidural space is concentration-dependent. After
      insertion of a lumbar epidural catheter, patients received epidural diamorphine 3
      mg either as a high-volume, low-concentration solution (group A) or a low-volume,
      high-concentration solution (group B). The concentration of diamorphine was
      determined by the response of the previous patient in the same group using up
      down sequential allocation. Pain corresponding to the previous contraction was
      assessed using a 100-mm visual analogue score and effective analgesia was defined
      as </=10 mm within 30 min of epidural injection. RESULTS: There was no
      significant difference in EC50 for diamorphine between the groups: the difference
      was 15.0 microg ml(-1) (95% CI -40.3 to 10.3). The EC50 for group A was 237.5
      microg ml(-1) (95% CI 221.2 to 253.8) and the EC50 for group B was 252.5 microg
      ml(-1) (95% CI 232.2 to 272.8). The EC50 ratio was 0.95 (95% CI 0.87 to 1.06).
      The groups exhibited parallelism (P=0.98). The overall EC50 for all data was
      244.2 microg ml(-1) (95% CI 230.8 to 257.2). CONCLUSION: We conclude that
      diamorphine provides analgesia in labour by a concentration-dependent effect.

PMID- 15556965
TI  - Effects of halothane, sevoflurane and propofol on left ventricular diastolic
      function in humans during spontaneous and mechanical ventilation.
AB  - BACKGROUND: There is limited knowledge of the effects of anaesthetics on left
      ventricular (LV) diastolic function in humans. Our aim was to evaluate these
      effects in humans free from cardiovascular disease. METHODS: Sixty patients (aged
      18-47 yr) who had no history or signs of cardiovascular disease were randomized
      to receive general anaesthesia with halothane, sevoflurane or propofol.
      Echocardiography was performed at baseline and during spontaneous respiration at
      1 minimum alveolar concentration (MAC) of the inhalational agents or propofol 4
      microg ml(-1) (step 1), and repeated during positive-pressure ventilation with 1
      and 1.5 MAC of the inhalational agents or with propofol 4 and 6 microg ml(-1)
      (steps 2a and 2b). Analysis of echocardiographic measurements focused on heart
      rate corrected isovolumic relaxation time (IVRT(c)) and early diastolic peak
      velocity of the lateral mitral annulus (E(a)). RESULTS: IVRT(c) decreased from
      baseline to step 1 in the halothane group (82 [95% CI, 76-88] ms and 74 [95% CI,
      68-80] ms respectively; P=0.02), remained stable in the sevoflurane group (78
      [95% CI, 72-83] ms and 73 [95% CI, 67-81] ms; n.s.) and increased in the propofol
      group (80 [95% CI, 74-86] ms and 92 [95% CI, 84-102] ms; P=0.02). E(a) decreased
      in the propofol group only (18.8 [95% CI, 16.5-19.9] cm s(-1) and 16.0 [95% CI,
      14.9-17.9] cm s(-1); P=0.003). From step 2a to step 2b, IVRT(c) increased further
      in the propofol group (109 [95% CI, 99-121] ms and 119 [95% CI, 99-135] ms;
      P=0.04) but remained stable in the other two groups. E(a) did not change from
      step 2a to step 2b. CONCLUSIONS: Halothane and sevoflurane did not impair LV
      relaxation, whereas propofol caused a mild impairment. However, the impairment by
      propofol was of a magnitude that is unlikely to cause clinical diastolic
      dysfunction.

PMID- 15556966
TI  - Preconditioning with sevoflurane decreases PECAM-1 expression and improves one
      year cardiovascular outcome in coronary artery bypass graft surgery.
AB  - BACKGROUND: Cardiac preconditioning is thought to be involved in the observed
      decreased coronary artery reocclusion rate in patients with angina preceding
      myocardial infarction. We prospectively examined whether preconditioning by
      sevoflurane would decrease late cardiac events in patients undergoing coronary
      artery bypass graft (CABG) surgery. METHODS: Seventy-two patients scheduled for
      elective CABG surgery were randomized to preconditioning by sevoflurane (10 min
      at 4 vol%) or placebo. For all patients, follow-up of adverse cardiac events was
      obtained 6 and 12 months after surgery. Transcript levels for platelet
      endothelial cell adhesion molecule-1 (PECAM-1/CD31), catalase and heat shock
      protein 70 (Hsp70) were determined in atrial biopsies after sevoflurane
      preconditioning. RESULTS: Pharmacological preconditioning by sevoflurane reduced
      the incidence of late cardiac events during the first year after CABG surgery
      (sevoflurane 3% vs 17% in the placebo group, log-rank test, P=0.038). One patient
      in the sevoflurane group and three patients in the placebo group experienced new
      episodes of congestive heart failure and three additional patients had coronary
      artery reocclusion. Perioperative peak concentrations for myocardial injury
      markers were higher in patients with subsequent late cardiac events [NTproBNP,
      9031 (4125) vs 3049 (1906) ng litre(-1), P<0.001; cTnT, 1.31 (0.88) vs 0.46
      (0.29) microg litre(-1), P<0.001]. Transcript levels were reduced for PECAM-1 and
      increased for catalase but unchanged for Hsp70 in atrial biopsies after
      sevoflurane preconditioning. CONCLUSIONS: This prospective randomized clinical
      study provides evidence of a protective role for pharmacological preconditioning
      by sevoflurane in late cardiac events in CABG patients, which may be related to
      favourable transcriptional changes in pro- and antiprotective proteins.

PMID- 15556967
TI  - Release of tumour necrosis factor alpha (TNFalpha) by TNFalpha cleaving enzyme
      (TACE) in response to septic stimuli in vitro.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNFalpha), in its soluble form
      (solTNF), has been well described as an important cytokine in inflammatory states
      including sepsis. The transmembrane precursor of solTNF, membrane-bound TNFalpha
      (memTNF), is cleaved by TNFalpha cleaving enzyme (TACE), the regulation of which
      is poorly understood. We hypothesized that the diversity of clinical features
      seen with sepsis caused by different organisms may be a result of differential
      regulation of TACE. Therefore, we measured these proteins in models of sepsis
      using flow cytometric methods that we have developed. METHODS: Surface protein
      expression of memTNF and TACE, and TACE catalytic activity were measured in human
      monocytes by flow cytometry following cell stimulation by lipopolysaccharide
      (LPS), zymosan (a yeast cell wall product) or heat-inactivated Neisseria
      meninigitidis. RESULTS: Unstimulated human monocytes express memTNF on the cell
      surface (mean fluorescence intensity, MFI 131) and this is down-regulated
      initially in response to LPS (MFI 57) but then recovers to exceed the resting
      protein expression (MFI 614). TACE protein is also present on the surface of
      resting cells (MFI 389) but is catalytically inactive until cell stimulation.
      Stimulation of monocytes with LPS, zymosan and Neisseria meningitidis produced
      different patterns of TACE activation with time. CONCLUSIONS: The regulation of
      memTNF by TACE on monocytes is an important regulatory event in the pro
      inflammatory cytokine cascade. As monocytes are important in the inflammatory
      cascade, we suggest that the control of memTNF and TACE activity on monocytes may
      play a role in the pathophysiology of sepsis.

PMID- 15556968
TI  - Bacterial lipid modification of proteins for novel protein engineering
      applications.
AB  - Functioning of proteins efficiently at the solid-liquid interface is critical to
      not only biological but also modern man-made systems such as ELISA, liposomes and
      biosensors. Anchoring hydrophilic proteins poses a major challenge in this
      regard. Lipid modification, N-acyl-S-diacylglyceryl-Cys, providing an N-terminal
      hydrophobic membrane anchor is a viable solution that bacteria have successfully
      evolved but remains unexploited. Based on the current understanding of this
      ubiquitous and unique bacterial lipid modification it is possible to use
      Escherichia coli, the popular recombinant protein expression host, for converting
      a non-lipoprotein to a lipoprotein with a hydrophobic anchor at the N-terminal
      end. We report two strategies applicable to non-lipoproteins (with or without
      signal sequences) employing minimal sequence change. Taking periplasmic Shigella
      apyrase as an example, its signal sequence was engineered to include a lipobox,
      an essential determinant for lipid modification, or its mature sequence was fused
      to the signal sequence of abundant outer membrane lipoprotein, Lpp. Lipid
      modification was proved by membrane localization, electrophoretic mobility shift
      and mass spectrometric analysis. Substrate specificity and specific activity
      measurements indicated functional integrity after modification. In conclusion, a
      convenient protein engineering strategy for converting non-lipoprotein to
      lipoprotein for commercial application has been devised and tested successfully.

PMID- 15556969
TI  - Engineering the xenobiotic substrate specificity of maize glutathione S
      transferase I.
AB  - Glutathione S-transferases (GSTs) are a heterogeneous family of enzymes that
      catalyse the conjugation of glutathione (GSH) to electrophilic sites on a variety
      of hydrophobic substrates. In the present study three amino acid residues (Trp12,
      Phe35 and Ile118) of the xenobiotic binding site (H-site) of maize GST I were
      altered in order to evaluate their contribution to substrate binding and
      catalysis. These residues are not conserved and hence may affect substrate
      specificity and/or product dissociation. The results demonstrate that these
      residues are important structural moieties that modulate an enzyme's catalytic
      efficiency and specificity. Phe35 and Ile118 also participate in k(cat)
      regulation by affecting the rate-limiting step of the catalytic reaction. The
      effect of temperature on the catalytic activity of the wild-type and mutant
      enzymes was also investigated. Biphasic Arrhenius and Eyring plots for the wild
      type enzyme showed an apparent transition temperature at 35 degrees C, which
      seems to be the result of a change in the rate-limiting step of the catalytic
      reaction. Thermodynamic analysis of the activity data showed that the activation
      energy increases at low temperatures, whereas the entropy change seems to be the
      main determinant that contributes to the rate-limiting step at high temperatures.

PMID- 15556970
TI  - Senescence of human skeletal muscle impairs the local inflammatory cytokine
      response to acute eccentric exercise.
AB  - The impact of aging on the cytokine response of human skeletal muscle to exercise
      induced injury remains poorly understood. We enrolled physically active, young
      (23-35 years old, n=15) and old (66-78 years old, n=15) men to perform 45 min of
      downhill running (16% descent) at 75% VO2max. Biopsies of vastus lateralis were
      obtained 24 h before and 72 h after acute eccentric exercise. Transcripts for
      inflammatory (TNF-alpha, IL-1beta) and anti-inflammatory cytokines (IL-6, TGF
      beta1) were quantified by real-time PCR. Before exercise, cytokine transcripts
      did not differ with age. At old age, exercise induced a blunted accumulation of
      transcripts encoding the pan-leukocyte surface marker CD18 (young: 10.1-fold
      increase, P<0.005; old: 4.7-fold increase, P=0.02; young vs. old: P<0.05). In
      both age groups, CD18 transcript accumulation strongly correlated with TNF-alpha
      (young, r=0.87, P<0.001; old, r=0.72, P=0.002) and TGF-beta1 transcript
      accumulation (young, r=0.80, P<0.001; old, r=0.64, P=0.008). At old age, there
      was no correlation between IL-1beta and CD18 transcript accumulation.
      Furthermore, exercise induced IL-6 transcript accumulation in young (3.6-fold,
      P=0.057) but not in old men. Our results suggest that aging impairs the adaptive
      response of human skeletal muscle to eccentric exercise by differential
      modulation of a discrete set of inflammatory and anti-inflammatory cytokine
      genes.

PMID- 15556971
TI  - CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule.
AB  - Carbon monoxide (CO) is emerging as an important and versatile mediator of
      physiological processes to the extent that treatment of animals with exogenous CO
      gas has beneficial effects in a range of vascular- and inflammatory-related
      disease models. The recent discovery that certain transition metal carbonyls
      function as CO-releasing molecules (CO-RMs) in biological systems highlighted the
      potential of exploiting this and similar classes of compounds as a stratagem to
      deliver CO for therapeutic purposes. Here we describe the biochemical features
      and pharmacological actions of a newly identified water-soluble CO releaser (CORM
      A1) that, unlike the first prototypic molecule recently described (CORM-3), does
      not contain a transition metal and liberates CO at a much slower rate under
      physiological conditions. Using a myoglobin assay and an amperometric CO
      electrode, we demonstrated that the release of CO from CORM-A1 is both pH- and
      temperature-dependent with a half-life of approximately 21 min at 37 degrees C
      and pH 7.4. In isolated aortic rings, CORM-A1 promoted a gradual but profound
      concentration-dependent vasorelaxation over time, which was highly amplified by
      YC-1 (1 microM) and attenuated by ODQ, a stimulator and inhibitor of guanylate
      cyclase, respectively. Similarly, administration of CORM-A1 (30 micromol/kg i.v.)
      in vivo produced a mild decrease in mean arterial pressure, which was markedly
      potentiated by pretreatment with YC-1 (1.2 micromol/kg i.v.). Interestingly, an
      inactive form of CORM-A1 that is incapable of releasing CO failed to promote both
      vasorelaxation and hypotension, thus directly implicating CO as the mediator of
      the observed pharmacological effects. Our results reveal that the bioactivities
      exerted by CORM-A1 reflect its intrinsic biochemical behavior of a slow CO
      releaser, which may be advantageous in the treatment of chronic conditions that
      require CO to be delivered in a carefully controlled manner.

PMID- 15556972
TI  - Erythropoietin protects from axotomy-induced degeneration of retinal ganglion
      cells by activating ERK-1/-2.
AB  - Apart from its hematopoietic function, erythropoietin (Epo) exerts
      neuroprotective activity upon reduced oxygenation or ischemia of brain, retina,
      and spinal cord. To examine whether Epo has an impact on the retrograde
      degeneration of retinal ganglion cells (RGCs) following optic nerve transection
      in vivo, we made use of our transgenic mouse line tg21 that constitutively
      expresses human Epo preferentially in neuronal cells without inducing
      polycythemia. We show that the tg21 retina expresses human Epo and that RGCs in
      this mouse line carry the Epo receptor. Upon axotomy, the RGCs of Epo transgenic
      tg21 mice were protected against degeneration, as compared with wild-type control
      animals. Western blot analysis revealed decreased phosphorylation levels of STAT
      5 and reduced expression of Bcl-XL in RGCs of axotomized tg21 animals, suggesting
      that the corresponding pathways are not crucial for Epo's neuroprotective
      activity. Increased phosphorylation levels of ERK-1/-2 and Akt, as well as
      decreased caspase-3 activity, however, were observed in injured tg21 retinae.
      Injection of selective inhibitors of ERK-1/-2 (PD98059) or Akt (Wortmannin)
      pathways into the vitreous space revealed that transgenic Epo protected the RGCs
      by a pathway involving ERK-1/-2 but not Akt. In view that axotomy-induced
      degeneration of RGC occurs slowly, and considering the earlier data on the safety
      and efficacy of Epo in human stroke patients, we predict the clinical
      implementation of recombinant human Epo not only in patients with acute ischemic
      stroke, but also with more delayed degenerative neurological diseases.

PMID- 15556973
TI  - Measuring unfolding of proteins in the presence of denaturant using fluorescence
      correlation spectroscopy.
AB  - IFABP is a small (15 kDa) protein consisting mostly of antiparallel beta-strands
      that surround a large cavity into which ligands bind. We have previously used FCS
      to show that the native protein, labeled with fluorescein, exhibits dynamic
      fluctuation with a relaxation time of 35 micros. Here we report the use of FCS to
      study the unfolding of the protein induced by guanidine hydrochloride. Although
      the application of this technique to measure diffusion coefficients and molecular
      dynamics is straightforward, the FCS results need to be corrected for both
      viscosity and refractive index changes as the guanidine hydrochloride
      concentration increases. We present here a detailed study of the effects of
      viscosity and refractive index of guanidine hydrochloride solutions to calibrate
      FCS data. After correction, the increase in the diffusion time of IFABP
      corresponds well with the unfolding transition monitored by far ultraviolet
      circular dichroism. We also show that the magnitude of the 35 micros phase,
      reflecting the conformational fluctuation in the native state, decreases sharply
      as the concentration of denaturant increases and the protein unfolds. Although
      FCS experiments indicate that the unfolded state at pH 2 is rather compact and
      native-like, the radius in the presence of guanidine hydrochloride falls well
      within the range expected for a random coil.

PMID- 15556974
TI  - Axis curvature and ligand induced bending in the CAP-DNA oligomers.

PMID- 15556975
TI  - Rapid intracellular TEA block of the KcsA potassium channel.
AB  - Intracellular tetraethylammonium (TEA) inhibition was studied at the single
      channel level in the KcsA potassium channel reconstituted in planar lipid
      bilayers. TEA acts as a fast blocker (resulting in decreased current amplitude)
      with an affinity in the 75 mM range even at high bandwidth. Studies over a wide
      voltage range reveal that TEA block has a complex voltage-dependence that also
      depends on the ionic conditions. These observations are examined in the context
      of permeation models to extend our understanding of the coupling between permeant
      ions and TEA blockade.

PMID- 15556976
TI  - Micro magnetic tweezers for nanomanipulation inside live cells.
AB  - This study reports the design, realization, and characterization of a multi-pole
      magnetic tweezers that enables us to maneuver small magnetic probes inside living
      cells. So far, magnetic tweezers can be divided into two categories: I), tweezers
      that allow the exertion of high forces but consist of only one or two poles and
      therefore are capable of only exerting forces in one direction; and II), tweezers
      that consist of multiple poles and allow exertion of forces in multiple
      directions but at very low forces. The magnetic tweezers described here combines
      both aspects in a single apparatus: high forces in a controllable direction. To
      this end, micron scale magnetic structures are fabricated using cleanroom
      technologies. With these tweezers, magnetic flux gradients of nablaB = 8 x 10(3)
      T m(-1) can be achieved over the dimensions of a single cell. This allows
      exertion of forces up to 12 pN on paramagnetic probes with a diameter of 350 nm,
      enabling us to maneuver them through the cytoplasm of a living cell. It is
      expected that with the current tweezers, picoNewton forces can be exerted on
      beads as small as 100 nm.

PMID- 15556977
TI  - Electroendocytosis: exposure of cells to pulsed low electric fields enhances
      adsorption and uptake of macromolecules.
AB  - This study demonstrates alteration of cell surface, leading to enhanced
      adsorption of macromolecules (bovine serum albumin (BSA), dextran, and DNA),
      after the exposure of cells to unipolar pulsed low electric fields (LEF).
      Modification of the adsorptive properties of the cell membrane also stems from
      the observation of LEF-induced cell-cell aggregation. Analysis of the adsorption
      isotherms of BSA-fluorescein isothiocyanate (FITC) to the surface of COS 5-7
      cells reveals that the stimulated adsorption can be attributed to LEF-induced
      increase in the capacity of both specific and nonspecific binding. The enhanced
      adsorption was consequently followed by increased uptake. At 20 V/cm the maximal
      binding and subsequent uptake of BSA-FITC attached to specific sites are 6.5- and
      7.4-fold higher than in controls, respectively. The nonspecific LEF-induced
      binding and uptake of BSA are 34- and 5.2-fold higher than in controls. LEF
      enhanced adsorption is a temperature-independent process, whereas LEF-induced
      uptake is a temperature-dependent one that is abolished at 4 degrees C. The
      stimulation of adsorption and uptake is reversible, revealing similar decay
      kinetics at room temperature. It is suggested that electrophoretic segregation of
      charged components in the outer leaflet of the cell membrane is responsible for
      both enhanced adsorption and stimulated uptake via changes of the membrane
      elastic properties that enhance budding and fission processes.

PMID- 15556978
TI  - Force history dependence of receptor-ligand dissociation.
AB  - Receptor-ligand bonds that mediate cell adhesion are often subjected to forces
      that regulate their dissociation via modulating off-rates. Off-rates control how
      long receptor-ligand bonds last and how much force they withstand. One should
      therefore be able to determine off-rates from either bond lifetime or unbinding
      force measurements. However, substantial discrepancies exist between the force
      dependence of off-rates derived from the two types of measurements even for the
      same interactions, e.g., selectins dissociating from their ligands, which mediate
      the tethering and rolling of leukocytes on vascular surfaces during inflammation
      and immune surveillance. We used atomic force microscopy to measure survival
      times of P-selectin dissociating from P-selectin glycoprotein ligand 1 or from an
      antibody in both bond lifetime and unbinding force experiments. By a new method
      of data analysis, we showed that the discrepancies resulted from the assumption
      that off-rates were functions of force only. The off-rates derived from forced
      dissociation data depended not only on force but also on the history of force
      application. This finding provides a new paradigm for understanding how force
      regulates receptor-ligand interactions.

PMID- 15556979
TI  - Theory of optical spectra of photosystem II reaction centers: location of the
      triplet state and the identity of the primary electron donor.
AB  - Based on the structural analysis of photosystem II of Thermosynechococcus
      elongatus, a detailed calculation of optical properties of reaction-center (D1
      D2) complexes is presented applying a theory developed previously. The
      calculations of absorption, linear dichroism, circular dichroism, fluorescence
      spectra, all at 6 K, and the temperature-dependence of the absorption spectrum
      are used to extract the local optical transition energies of the reaction-center
      pigments, the so-called site energies, from experimental data. The site energies
      are verified by calculations and comparison with seven additional independent
      experiments. Exciton relaxation and primary electron transfer in the reaction
      center are studied using the site energies. The calculations are used to
      interpret transient optical data. Evidence is provided for the accessory
      chlorophyll of the D1-branch as being the primary electron donor and the location
      of the triplet state at low temperatures.

PMID- 15556980
TI  - A double-deletion method to quantifying incremental binding energies in proteins
      from experiment: example of a destabilizing hydrogen bonding pair.
AB  - The contribution of a specific hydrogen bond in apoflavodoxin to protein
      stability is investigated by combining theory, experiment and simulation.
      Although hydrogen bonds are major determinants of protein structure and function,
      their contribution to protein stability is still unclear and widely debated. The
      best method so far devised to estimate the contribution of side-chain
      interactions to protein stability is double mutant cycle analysis, but the
      interaction energies so derived are not identical to incremental binding energies
      (the energies quantifying net contributions of two interacting groups to protein
      stability). Here we introduce double-deletion analysis of 'isolated' residue
      pairs as a means to precisely quantify incremental binding. The method is
      exemplified by studying a surface-exposed hydrogen bond in a model protein
      (Asp96/Asn128 in apoflavodoxin). Combined substitution of these residues by
      alanines slightly destabilizes the protein due to a decrease in hydrophobic
      surface burial. Subtraction of this effect, however, clearly indicates that the
      hydrogen-bonded groups in fact destabilize the native conformation. In addition,
      molecular dynamics simulations and classic double mutant cycle analysis explain
      quantitatively that, due to frustration, the hydrogen bond must form in the
      native structure because when the two groups get approximated upon folding their
      binding becomes favorable. We would like to remark that 1), this is the first
      time the contribution of a specific hydrogen bond to protein stability has been
      measured by experiment; and 2), more hydrogen bonds need to be analyzed to draw
      general conclusions on protein hydrogen bond energetics. To that end, the double
      deletion method should be of help.

PMID- 15556981
TI  - Misfolding pathways of the prion protein probed by molecular dynamics
      simulations.
AB  - Although the cellular monomeric form of the benign prion protein is now well
      characterized, a model for the monomer of the misfolded conformation (PrP(Sc))
      remains elusive. PrP(Sc) quickly aggregates into highly insoluble fibrils making
      experimental structural characterization very difficult. The tendency to
      aggregation of PrP(Sc) in aqueous solution implies that the monomer fold must be
      hydrophobic. Here, by using molecular dynamics simulations, we have studied the
      cellular mouse prion protein and its D178N pathogenic mutant immersed in a
      hydrophobic environment (solution of CCl4), to reveal conformational changes
      and/or local structural weaknesses of the prion protein fold in unfavorable
      structural and thermodynamic conditions. Simulations in water have been also
      performed. Although observing in general a rather limited conformation activity
      in the nanosecond timescale, we have detected a significant weakening of the
      antiparallel beta-sheet of the D178N mutant in CCl4 and to a less extent in
      water. No weakening is observed for the native prion protein. The increase of
      beta-structure in the monomer, recently claimed as evidence for misfolding to
      PrP(Sc), has been also observed in this study irrespective of the thermodynamic
      or structural conditions, showing that this behavior is very likely an intrinsic
      characteristic of the prion protein fold.

PMID- 15556982
TI  - The transmembrane domain of the acetylcholine receptor: insights from simulations
      on synthetic peptide models.
AB  - We have studied the structure and properties of a bundle of alpha-helical
      peptides embedded in a 1,2-dimyristoyl-3-phosphatidylcholine phospholipid bilayer
      by molecular dynamics simulations. The bundle of five transmembrane deltaM2
      segments constitutes the model for the pore region of the nicotinic acetylcholine
      receptor, which is the neurotransmitter-gated ion-channel responsible for the
      fast propagation of electrical signals between cells at the nerve-muscle synapse.
      The deltaM2 segments were shown to oligomerize in biomembranes resulting in ion
      channel activity with characteristics similar to the native protein, and the
      structure of the isolated peptides was studied in 1,2-dimyristoyl-3
      phosphatidylcholine bilayers and micelles by NMR experiments (Opella, S. J., et
      al. 1999. Nat. Struct. Biol. 6:374-379). Our analyses indicate that the
      structure, helix tilt, and the overall shape of the channel are in good agreement
      with the NMR experiments and the proposed model for the channel, which we show is
      formed by rings of functional residues. The studied geometry resulted in a closed
      pore state, where the channel is partially dehydrated at the hydrophobic
      extracellular half and the extracellular mouth of the channel blocked by the
      hydrocarbon chains of Arg+ residues. The arginine amino acids form intermolecular
      salt-bridges with the C-terminus, which contribute as well to the bundle
      stabilization.

PMID- 15556984
TI  - Observation of magnetoreceptive behavior in a multicellular magnetotactic
      prokaryote in higher than geomagnetic fields.
AB  - The magnetotactic multicellular prokaryote (MMP), a motile aggregate of bacterial
      cells, is known to exhibit an unusual "ping-pong" motility in magnetic fields
      greater than the earth's field. This motility is characterized by rapid
      excursions, opposite the direction of an applied magnetic field, and slower
      returns along the direction of the magnetic field. We have carried out detailed
      observations of the time and spatial dependence of the ping-pong motility and
      find 1), the outward and return excursions exhibit a uniform deceleration and
      acceleration, respectively; 2), the probability per unit time of an MMP
      undergoing a ping-pong excursion increases monotonically with the field strength;
      and 3), the outward excursions exhibit a very unusual distance distribution which
      is dependent on the magnetic field strength. At any given field strength, a
      characteristic distance is observed, below which very few excursions occur.
      Beyond this distance, there is a rapid increase in the number of excursions with
      an exponentially decaying distribution. These observations cannot be explained by
      conventional magnetotaxis, i.e., a physical directing torque on the organism, and
      suggest a magnetoreceptive capability of the MMP.

PMID- 15556983
TI  - Forces during bacteriophage DNA packaging and ejection.
AB  - The conjunction of insights from structural biology, solution biochemistry,
      genetics, and single-molecule biophysics has provided a renewed impetus for the
      construction of quantitative models of biological processes. One area that has
      been a beneficiary of these experimental techniques is the study of viruses. In
      this article we describe how the insights obtained from such experiments can be
      utilized to construct physical models of processes in the viral life cycle. We
      focus on dsDNA bacteriophages and show that the bending elasticity of DNA and its
      electrostatics in solution can be combined to determine the forces experienced
      during packaging and ejection of the viral genome. Furthermore, we quantitatively
      analyze the effect of fluid viscosity and capsid expansion on the forces
      experienced during packaging. Finally, we present a model for DNA ejection from
      bacteriophages based on the hypothesis that the energy stored in the tightly
      packed genome within the capsid leads to its forceful ejection. The predictions
      of our model can be tested through experiments in vitro where DNA ejection is
      inhibited by the application of external osmotic pressure.

PMID- 15556985
TI  - The effect of cellular receptor diffusion on receptor-mediated viral binding
      using Brownian adhesive dynamics (BRAD) simulations.
AB  - Brownian adhesive dynamics (BRAD) is a new method for simulating the attachment
      of viruses to cell surfaces. In BRAD, the motion of the virus is subject to
      stochastic bond formation and breakage, and thermal motion owing to collisions
      from the solvent. In the model, the virus is approximated as a rigid sphere and
      the cell surface is approximated as a rigid plane coated with receptors. In this
      article, we extend BRAD to allow for the mobility of receptors in the plane of
      the membrane, both before and after they are ligated by viral attachment
      proteins. Allowing the proteins to move within the membrane produced several
      differences in behavior from when the receptors are immobilized. First, the mean
      steady-state bond number is unaffected by changes in cellular receptor density
      because proteins are now free to diffuse into the contact area, and the extent of
      binding is dictated by the availability of viral attachment proteins. Second, the
      time required to reach steady-state binding increases as both the cellular
      receptor number decreases and the receptor mobility decreases. This is because
      receptor diffusion is a slower process than the binding kinetics of the proteins.
      Decreasing the rate of protein binding was found to decrease the fraction of
      viruses bound to steady state, but not the extent of binding for those viruses
      that were bound. Increasing the binding rate increased the fraction of viruses
      bound, until no further viruses could bind. Alterations in receptor binding
      kinetics had no discernable effect on the mean steady-state bond number between
      virus and cell, because interactions were of sufficiently high affinity that all
      available receptor-viral attachment proteins were destined to bind at steady
      state.

PMID- 15556986
TI  - Improved "optical highlighter" probes derived from discosoma red fluorescent
      protein.
AB  - The tetrameric red fluorescent protein, DsRed, undergoes a rapid red to green
      color change evoked by short wavelength (lambda < 760 nm) femtosecond irradiation
      -a phenomenon that underpins the application of DsRed as an "optical highlighter"
      probe for tracking live cells, organelles, and fusion proteins. This color change
      results from selective bleaching of the "mature" red-emitting species of DsRed
      and an enhancement of emission from the "immature" green species, likely caused
      by dequenching of fluorescence resonance energy transfer occurring within the
      protein tetramer. Here, we have examined the role of residues known to influence
      the rate and completeness of chromophore maturation on the cellular and
      biophysical properties of DsRed mutants. Surprisingly, a single amino acid
      mutation (N42Q) with increased basal green emission yet rapid chromophore
      maturation displayed a multiphoton-evoked color change that was brighter, more
      consistent, more vivid, and easier to evoke than DsRed, despite the larger
      proportion of green chromophores. Rapidly maturing mutants with more complete
      chromophore maturation, exhibited little color change and increased resistance to
      multiphoton bleaching. We describe improved optical and cell biological
      properties for two DsRed-derived variants which we showcase in photolabeling
      studies, and discuss these data in terms of implications for fluorescence
      resonance energy transfer-based probes.

PMID- 15556987
TI  - Calcium mobilization and spontaneous transient outward current characteristics
      upon agonist activation of P2Y2 receptors in smooth muscle cells.
AB  - A quantitative model is provided that links the process of metabotropic receptor
      activation and sequestration to the generation of inositol 1,4,5-trisphosphate,
      the subsequent release of calcium from the central sarcoplasmic reticulum, and
      the consequent release of calcium from subsarcolemma sarcoplasmic reticulum that
      acts on large-conductance potassium channels to generate spontaneous transient
      outward currents (STOCs). This model is applied to the case of STOC generation in
      vascular A7r5 smooth muscle cells that have been transfected with a chimera of
      the P2Y(2) metabotropic receptor and green fluorescent protein (P2Y(2)-GFP) and
      exposed to the P2Y(2) receptor agonist uridine 5'-triphosphate. The extent of
      P2Y(2)-GFP sequestration from the membrane on exposure to uridine 5'
      triphosphate, the ensuing changes in cytosolic calcium concentration, as well as
      the interval between STOCs that are subsequently generated, are used to determine
      parameter values in the model. With these values, the model gives a good
      quantitative prediction of the dynamic changes in STOC amplitude observed upon
      activation of metabotropic P2Y(2) receptors in the vascular smooth muscle cell
      line.

PMID- 15556988
TI  - Intrinsic curvature in the VP1 gene of SV40: comparison of solution and gel
      results.
AB  - DNA restriction fragments that are stably curved are usually identified by
      polyacrylamide gel electrophoresis because curved fragments migrate more slowly
      than normal fragments containing the same number of basepairs. In free solution,
      curved DNA molecules can be identified by transient electric birefringence (TEB)
      because they exhibit rotational relaxation times that are faster than those of
      normal fragments of the same size. In this article, the results observed in free
      solution and in polyacrylamide gels are compared for a highly curved 199-basepair
      (bp) restriction fragment taken from the VP1 gene in Simian Virus 40 (SV40) and
      various sequence mutants and insertion derivatives. The TEB method of overlapping
      fragments was used to show that the 199-bp fragment has an apparent bend angle of
      46 +/- 2 degrees centered at sequence position 1922 +/- 2 bp. Four unphased A-
      and T-tracts and a mixed A3T4-tract occur within a span of approximately 60 bp
      surrounding the apparent bend center; for brevity, this 60-bp sequence element is
      called a curvature module. Modifying any of the A- or T-tracts in the curvature
      module by site-directed mutagenesis decreases the curvature of the fragment;
      replacing all five A- and T-tracts by random-sequence DNA causes the 199-bp
      mutant to adopt a normal conformation, with normal electrophoretic mobilities and
      birefringence relaxation times. Hence, stable curvature in this region of the VP1
      gene is due to the five unphased A- and T- tracts surrounding the apparent bend
      center. Discordant solution and gel results are observed when long inverted
      repeats are inserted within the curvature module. These insertion derivatives
      migrate anomalously slowly in polyacrylamide gels but have normal, highly
      flexible conformations in free solution. Discordant solution and gel results are
      not observed if the insert does not contain a long inverted repeat or if the long
      inverted repeat is added to the 199-bp fragment outside the curvature module. The
      results suggest that long inverted repeats can form hairpins or cruciforms when
      they are located within a region of the helix backbone that is intrinsically
      curved, leading to large mobility anomalies in polyacrylamide gels.
      Hairpin/cruciform formation is not observed in free solution, presumably because
      of rapid conformational exchange. Hence, DNA restriction fragments that migrate
      anomalously slowly in polyacrylamide gels are not necessarily stably curved in
      free solution.

PMID- 15556989
TI  - Molecular packing and packing defects in helical membrane proteins.
AB  - The packing of helices spanning lipid bilayers is crucial for the stability and
      function of alpha-helical membrane proteins. Using a modified Voronoi procedure,
      we calculated packing densities for helix-helix contacts in membrane spanning
      domains. Our results show that the transmembrane helices of protein channels and
      transporters are significantly more loosely packed compared with helices in
      globular proteins. The observed packing deficiencies of these membrane proteins
      are also reflected by a higher amount of cavities at functionally important
      sites. The cavities positioned along the gated pores of membrane channels and
      transporters are noticeably lined by polar amino acids that should be exposed to
      the aqueous medium when the protein is in the open state. In contrast, nonpolar
      amino acids surround the cavities in those protein regions where large
      rearrangements are supposed to take place, as near the hinge regions of
      transporters or at restriction sites of protein channels. We presume that the
      observed deficiencies of helix-helix packing are essential for the helical
      mobility that sustains the function of many membrane protein channels and
      transporters.

PMID- 15556990
TI  - Phosphatidylethanolamine-phosphatidylglycerol bilayer as a model of the inner
      bacterial membrane.
AB  - Phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) are the main lipid
      components of the inner bacterial membrane. A computer model for such a membrane
      was built of palmitoyloleoyl PE (POPE) and palmitoyloleoyl PG (POPG) in the
      proportion 3:1, and sodium ions (Na+) to neutralize the net negative charge on
      each POPG (POPE-POPG bilayer). The bilayer was simulated for 25 ns. A final 10-ns
      trajectory fragment was used for analyses. In the bilayer interfacial region,
      POPEs and POPGs interact readily with one another via intermolecular hydrogen (H)
      bonds and water bridges. POPE is the main H-bond donor in either PEPE or PEPG H
      bonds; PGPG H-bonds are rarely formed. Almost all POPEs are H-bonded and/or water
      bridged to either POPE or POPG but PE-PG links are favored. In effect, the atom
      packing in the near-the-interface regions of the bilayer core is tight. Na+ does
      not bind readily to lipids, and interlipid links via Na+ are not numerous.
      Although POPG and POPE comprise one bilayer, their bilayer properties differ. The
      average surface area per POPG is larger and the average vertical location of the
      POPG phosphate group is lower than those of POPE. Also, the alkyl chains of POPG
      are more ordered and less densely packed than the POPE chains. The main
      conclusion of this study is that in the PE-PG bilayer PE interacts more strongly
      with PG than with PE. This is a likely molecular-level event behind a regulating
      mechanism developed by the bacteria to control its membrane permeability and
      stability consisting in changes of the relative PG/PE concentration in the
      membrane.

PMID- 15556991
TI  - Dynamics of myosin-V processivity.
AB  - Myosin-V is an actin-associated processive molecular motor. Single molecule
      experiments revealed that myosin-V walks in a stepwise fashion with occasional
      backward steps. By combining the mechanical structure of the motor with the ATP
      hydrolysis kinetics, we construct a dynamical model that accounts for the
      stepwise processivity. The molecular properties of the protein chains connecting
      the myosin heads are important. A simple elastic model demonstrates that the
      stress transmitted from the leading head to the trailing head leads to net
      forward motion. The step-sizes are non-uniform. We also predict there are several
      substeps. The translational speed and step-size distributions are computed for
      several different conditions. The computed force-versus-velocity curve shows that
      under an external load, myosin-V slows down. However, the sizes of the steps
      remain the same.

PMID- 15556992
TI  - Real-time measurements of actin filament polymerization by total internal
      reflection fluorescence microscopy.
AB  - Understanding the mechanism of actin polymerization and its regulation by
      associated proteins requires an assay to monitor polymerization dynamics and
      filament topology simultaneously. The only assay meeting these criteria is total
      internal reflection fluorescence microscopy (Amann and Pollard, 2001; Fujiwara et
      al., 2002). The fluorescence signal is fourfold stronger with actin labeled on
      Cys-374 with Oregon green rather than rhodamine. To distinguish growth at barbed
      and pointed ends we used image drift correction and maximum intensity projections
      to reveal points where single N-ethylmaleimide inactivated myosins attach
      filaments to the glass coverslip. We estimated association rates at high actin
      concentrations and dissociation rates near and below the critical actin
      concentration. At the barbed end, the association rate constant for Mg-ATP-actin
      is 7.4 microM(-1) s(-1) and the dissociation rate constant is 0.89 s(-1). At the
      pointed end the association and dissociation rate constants are 0.56 microM(-1)
      s(-1) and 0.19 s(-1). When vitamin D binding protein sequesters all free
      monomers, ADP-actin dissociates from barbed ends at 1.4 s(-1) and from pointed
      ends at 0.16 s(-1) regardless of buffer nucleotide.

PMID- 15556993
TI  - Structural analysis of the inactive state of the Escherichia coli DNA polymerase
      clamp-loader complex.
AB  - Clamp-loader complexes are heteropentameric AAA+ ATPases that load sliding clamps
      onto DNA. The structure of the nucleotide-free Escherichia coli clamp loader had
      been determined previously and led to the proposal that the clamp-loader cycles
      between an inactive state, in which the ATPase domains form a closed ring, and an
      active state that opens up to form a "C" shape. The crystal structure was
      interpreted as being closer to the active state than the inactive state. The
      crystal structure of a nucleotide-bound eukaryotic clamp loader [replication
      factor C (RFC)] revealed a different and more tightly packed spiral organization
      of the ATPase domains, raising questions about the significance of the
      conformation seen earlier for the bacterial clamp loader. We describe crystal
      structures of the E. coli clamp-loader complex bound to the ATP analog ATPgammaS
      (at a resolution of 3.5 A) and ADP (at a resolution of 4.1 A). These structures
      are similar to that of the nucleotide-free clamp-loader complex. Only two of the
      three functional ATP-binding sites are occupied by ATPgammaS or ADP in these
      structures, and the bound nucleotides make no interfacial contacts in the
      complex. These results, along with data from isothermal titration calorimetry,
      molecular dynamics simulations, and comparison with the RFC structure, suggest
      that the more open form of the E. coli clamp loader described earlier and in the
      present work corresponds to a stable inactive state of the clamp loader in which
      the ATPase domains are prevented from engaging the clamp in the highly
      cooperative manner seen in the fully ATP-loaded RFC-clamp structure.

PMID- 15556994
TI  - Sarcolipin retention in the endoplasmic reticulum depends on its C-terminal RSYQY
      sequence and its interaction with sarco(endo)plasmic Ca(2+)-ATPases.
AB  - Sarcolipin (SLN) and phospholamban (PLN) are effective inhibitors of the
      sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). These homologous proteins
      differ at their N and C termini: the C-terminal Met-Leu-Leu in PLN is replaced by
      Arg-Ser-Tyr-Gln-Tyr in SLN. The role of the C-terminal sequence of SLN tagged N
      terminally with the FLAG epitope (NF-SLN) in endoplasmic reticulum (ER) retention
      was investigated by transfecting human embryonic kidney-293 cells with cDNAs
      encoding NF-SLN or a series of NF-SLN mutants in which C-terminal amino acids
      were deleted progressively. Immunofluorescence and immunoblotting of transfected
      cells by using anti-FLAG antibodies indicated that NF-SLN and PLN tagged at its N
      terminus with the FLAG epitope, even when overexpressed, were restricted to the
      ER. However, C-terminal truncation deletions of SLN, which lacked RSYQY, were not
      localized to ER and did not inhibit Ca(2+)-dependent Ca2+ uptake by SERCA. The
      shortest deletion constructs, NF-SLN 1-22 and NF-SLN 1-23, did not express stable
      protein products. However, all NF-SLN cDNA constructs, including NF-SLN 1-22 and
      NF-SLN 1-23, were expressed stably and localized to the ER when they were
      coexpressed with SERCA2a. These results show that NF-SLN subcellular distribution
      depends on SERCA coexpression and on its luminal, C-terminal RSYQY sequence. By
      using immunoprecipitation and MS, glucose-regulated protein 78/BiP and glucose
      regulated protein 94 were identified as proteins that interact with NF-SLN
      through the RSYQY sequence. Thus, in the absence of SERCA, retention of NF-SLN in
      the ER is mediated through its association with other components through the C
      terminal RSYQY sequence.

PMID- 15556995
TI  - Evolution of new nonantibody proteins via iterative somatic hypermutation.
AB  - B lymphocytes use somatic hypermutation (SHM) to optimize immunoglobulins.
      Although SHM can rescue single point mutations deliberately introduced into
      nonimmunoglobulin genes, such experiments do not show whether SHM can efficiently
      evolve challenging novel phenotypes requiring multiple unforeseeable mutations in
      nonantibody proteins. We have now iterated SHM over 23 rounds of fluorescence
      activated cell sorting to create monomeric red fluorescent proteins with
      increased photostability and far-red emissions (e.g., 649 nm), surpassing the
      best efforts of structure-based design. SHM offers a strategy to evolve
      nonantibody proteins with desirable properties for which a high-throughput
      selection or viable single-cell screen can be devised.

PMID- 15556996
TI  - The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1.
AB  - The toroidal damage checkpoint complex Rad9-Rad1-Hus1 (9-1-1) has been
      characterized as a sensor of DNA damage. Flap endonuclease 1 (FEN1) is a
      structure-specific nuclease involved both in removing initiator RNA from Okazaki
      fragments and in DNA repair pathways. FEN1 activity is stimulated by
      proliferating cell nuclear antigen (PCNA), a toroidal sliding clamp that acts as
      a platform for DNA replication and repair complexes. We show that 9-1-1 also
      binds and stimulates FEN1. Stimulation is observed on a variety of flap, nick,
      and gapped substrates simulating repair intermediates. Blocking 9-1-1 entry to
      the double strands prevents a portion of the stimulation. Like PCNA stimulation,
      9-1-1 stimulation cannot circumvent the tracking mechanism by which FEN1 enters
      the substrate; however, 9-1-1 does not substitute for PCNA in the stimulation of
      DNA polymerase beta. This suggests that 9-1-1 is a damage-specific activator of
      FEN1.

PMID- 15556997
TI  - Perceptual deficits in patients with impaired recognition of biological motion
      after temporal lobe lesions.
AB  - "Biological motion" may be defined by the pattern of movement of a small number
      of lights attached to the major joints of a human performing simple actions.
      Normal observers watching such displays immediately recognize a person and his or
      her actions. In the present study, we investigated the effects of lesions of
      anterior cortical regions on the perception of biological motion. We measured the
      performance on psychophysical static and motion tasks and on object and action
      recognition tests in four stroke patients who presented with a disorder of
      recognition of biological motion. We relate our results to the finding that
      neurons in the rostral part of the superior temporal gyrus (the superior temporal
      polysensory area) respond selectively to biological motion, and to the idea that
      the superior temporal polysensory area integrates the late stages of the dorsal
      and ventral cortical visual streams, as well as to recent functional MRI studies
      on biological motion.

PMID- 15556998
TI  - Reversible transdifferentiation of secretory epithelial cells into adipocytes in
      the mammary gland.
AB  - Mammalian breast adipose tissue is replaced by a milk-secreting gland during
      pregnancy; the reverse process takes place upon interruption of lactation.
      Morphological and bromodeoxyuridine studies provide indirect evidence that mouse
      mammary adipocytes transform into secretory epithelial cells during pregnancy and
      revert to adipocytes after lactation. By using the Cre-loxP recombination system
      we show that the mammary gland of whey acidic protein (WAP)-Cre/R26R mice, in
      which secretory epithelial cells express the lacZ gene during pregnancy, contains
      labeled adipocytes during involution. Conversely, adipocyte P2-Cre/R26R mice, in
      which adipocytes are labeled before pregnancy, contain labeled secretory
      epithelial cells during pregnancy. We conclude that reversible adipocyte-to
      epithelium and epithelium-to-adipocyte transdifferentiation occurs in the mammary
      gland of adult mice during pregnancy and lactation.

PMID- 15556999
TI  - Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia
      response element antagonist.
AB  - Vascular endothelial growth factor (VEGF) and its receptors have been implicated
      as key factors in tumor angiogenesis that are up-regulated by hypoxia. We
      evaluated the effects of DNA-binding small molecules on hypoxia-inducible
      transcription of VEGF. A synthetic pyrrole-imidazole polyamide designed to bind
      the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor
      (HIF) binding to HRE. In cultured HeLa cells, this resulted in a reduction of
      VEGF mRNA and secreted protein levels. The observed effects were polyamide
      specific and dose-dependent. Analysis of genome-wide effects of the HRE-specific
      polyamide revealed that a number of hypoxia-inducible genes were down-regulated.
      Pathway-based regulation of hypoxia-inducible gene expression with DNA-binding
      small molecules may represent a new approach for targeting angiogenesis.

PMID- 15557000
TI  - Halogen bonds in biological molecules.
AB  - Short oxygen-halogen interactions have been known in organic chemistry since the
      1950s and recently have been exploited in the design of supramolecular
      assemblies. The present survey of protein and nucleic acid structures reveals
      similar halogen bonds as potentially stabilizing inter- and intramolecular
      interactions that can affect ligand binding and molecular folding. A halogen bond
      in biomolecules can be defined as a short C-X...O-Y interaction (C-X is a carbon
      bonded chlorine, bromine, or iodine, and O-Y is a carbonyl, hydroxyl, charged
      carboxylate, or phosphate group), where the X...O distance is less than or equal
      to the sums of the respective van der Waals radii (3.27 A for Cl...O, 3.37 A for
      Br...O, and 3.50 A for I...O) and can conform to the geometry seen in small
      molecules, with the C-X...O angle approximately 165 degrees (consistent with a
      strong directional polarization of the halogen) and the X...O-Y angle
      approximately 120 degrees . Alternative geometries can be imposed by the more
      complex environment found in biomolecules, depending on which of the two types of
      donor systems are involved in the interaction: (i) the lone pair electrons of
      oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the
      delocalized pi -electrons of peptide bonds or carboxylate or amide groups. Thus,
      the specific geometry and diversity of the interacting partners of halogen bonds
      offer new and versatile tools for the design of ligands as drugs and materials in
      nanotechnology.

PMID- 15557002
TI  - Synthesis of galmic: a nonpeptide galanin receptor agonist.
AB  - Galanin is a neuropeptide with a wide variety of biological functions. Few
      nonpeptide ligands, capable of activating galanin receptors, are available today.
      Based on known pharmacophores of galanin and the tripeptidomimetic galnon, a
      combinatorial library was formulated, synthesized, and screened against the
      galanin receptor. An active compound, galmic, was identified and tested in vitro
      and in vivo for its affinity and efficacy at galanin receptors. The present work
      describes the total synthesis of galmic, the synthesis of its oxazole precursors,
      the coupling of the building blocks into a linear trimer, and the
      macrolactamization reaction.

PMID- 15557001
TI  - Solution structure of the CD3epsilondelta ectodomain and comparison with
      CD3epsilongamma as a basis for modeling T cell receptor topology and signaling.
AB  - Invariant CD3 subunit dimers (CD3epsilongamma, CD3epsilondelta, and CD3zetazeta)
      are the signaling components of the alphabeta T cell receptor (TCR). The recently
      solved structure of murine CD3epsilongamma revealed a unique side-to-side
      interface and central beta-sheets conjoined between the two C2-set Ig-like
      ectodomains, with the pairing of the parallel G strands implying a potential
      concerted piston-type movement for signal transduction. Although CD3gamma and
      CD3delta each dimerize with CD3epsilon, there are differential CD3 subunit
      requirements for receptor assembly and signaling among T lineage subpopulations,
      presumably mandated by structural differences. Here we present the solution
      structure of the heterodimeric CD3epsilondelta complex. Whereas the CD3epsilon
      subunit conformation is virtually identical to that in CD3epsilongamma, the
      CD3delta ectodomain adopts a C1-set Ig fold, with a narrower GFC front face beta
      sheet that is more parallel to the ABED back face than those beta-sheets in
      CD3epsilon and CD3gamma. The dimer interface between CD3delta and CD3epsilon is
      highly conserved among species and of similar character to that in
      CD3epsilongamma. Glycosylation sites in CD3delta are arranged such that the
      glycans may point away from the membrane, consistent with a model of TCR assembly
      that allows the CD3delta chain to be in close contact with the TCR alpha-chain.
      This and many other structural and biological features provide a basis for
      modeling putative TCR/CD3 extracellular domain associations. The fact that the
      two clusters of transmembrane helices, namely, the three CD3epsilon-CD3gamma
      TCRbeta segments and the five CD3epsilon-CD3delta-TCRalpha-CD3zeta-CD3zeta
      segments, are presumably centered beneath the G strand-paired CD3 heterodimers
      has important implications for TCR signaling.

PMID- 15557003
TI  - Dynamical resonance can account for seasonality of influenza epidemics.
AB  - Influenza incidence exhibits strong seasonal fluctuations in temperate regions
      throughout the world, concentrating the mortality and morbidity burden of the
      disease into a few months each year. The cause of influenza's seasonality has
      remained elusive. Here we show that the large oscillations in incidence may be
      caused by undetectably small seasonal changes in the influenza transmission rate
      that are amplified by dynamical resonance.

PMID- 15557004
TI  - Correction of kinetic and stability defects by tetrahydrobiopterin in
      phenylketonuria patients with certain phenylalanine hydroxylase mutations.
AB  - Phenylketonuria patients harboring a subset of phenylalanine hydroxylase (PAH)
      mutations have recently shown normalization of blood phenylalanine levels upon
      oral administration of the PAH cofactor tetrahydrobiopterin [(6R)-L-erythro
      5,6,7,8-tetrahydrobiopterin (BH4)]. Several hypotheses have been put forward to
      explain BH4 responsiveness, but the molecular basis for the corrective effect(s)
      of BH4 has not been understood. We have investigated the biochemical, kinetic,
      and structural changes associated with BH4-responsive mutations (F39L, I65T,
      R68S, H170D, E178G, V190A, R261Q, A300S, L308F, A313T, A373T, V388M, E390G,
      P407S, and Y414C). The biochemical and kinetic characterization of the 15 mutants
      studied points toward a multifactorial basis for the BH4 responsiveness; the
      mutants show residual activity (>30% of WT) and display various kinetic defects,
      including increased Km (BH4) and reduced cooperativity of substrate binding, but
      no decoupling of cofactor (BH4) oxidation. For some, BH4 seems to function
      through stabilization and protection of the enzyme from inactivation and
      proteolytic degradation. In the crystal structures of a phenylketonuria mutant,
      A313T, minor changes were seen when compared with the WT PAH structures,
      consistent with the mild effects the mutant has upon activity of the enzyme both
      in vitro and in vivo. Truncations made in the A313T mutant PAH form revealed that
      the N and C termini of the enzyme influence active site binding. Of fundamental
      importance is the observation that BH4 appears to increase Phe catabolism if at
      least one of the two heterozygous mutations has any residual activity remaining.

PMID- 15557005
TI  - Differentiation-induced replication-timing changes are restricted to AT-rich/long
      interspersed nuclear element (LINE)-rich isochores.
AB  - The replication timing of some genes is developmentally regulated, but the
      significance of replication timing to cellular differentiation has been difficult
      to substantiate. Studies have largely been restricted to the comparison of a few
      genes in established cell lines derived from different tissues, and most of these
      genes do not change replication timing. Hence, it has not been possible to
      predict how many or what types of genes might be subject to such control. Here,
      we have evaluated the replication timing of 54 tissue-specific genes in mouse
      embryonic stem cells before and after differentiation to neural precursors.
      Strikingly, genes residing within isochores rich in GC and poor in long
      interspersed nuclear elements (LINEs) did not change their replication timing,
      whereas half of genes within isochores rich in AT and long interspersed nuclear
      elements displayed programmed changes in replication timing that accompanied
      changes in gene expression. Our results provide direct evidence that
      differentiation-induced autosomal replication-timing changes are a significant
      part of mammalian development, provide a means to predict genes subject to such
      regulation, and suggest that replication timing may be more related to the
      evolution of metazoan genomes than to gene function or expression pattern.

PMID- 15557006
TI  - Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b
      antigen binding.
AB  - Heterogeneity among Helicobacter pylori strains in gastric epithelial adherence
      is postulated to contribute to pathogen fitness in the physiologically diverse
      human population. H. pylori adherence to ABO and Lewis b (Leb) blood group
      antigens in the human stomach is mediated by the blood group antigen-binding
      adhesin BabA. Approximately 70% of Swedish and U.S. H. pylori clinical isolates
      exhibit Leb binding, but here we show that the babA gene is present in each of 10
      Leb-nonbinding strains. Fluorescence microscopy identified occasional bacterial
      cells with a Leb-binding phenotype in populations of Leb-nonbinding strains.
      Thus, nonbinding seemed to be a metastable phenotype. To model metastable
      transition into the virulence-associated Leb-binding mode, Leb-binding clones
      were isolated from nonadherent strains by panning with Leb-magnetic beads and
      characterized. Strain 17875 has two babA genes, babA1 (silent) and babA2
      (expressed). We found that a babA2-cam derivative of strain 17875 regained Leb
      binding by recombination of the formerly silent babA1 gene into the expressed and
      partially homologous babB locus. The chimeric BabB/A adhesin binds Leb with an
      affinity similar to that of wild-type BabA adhesin, but its expression level was
      lower and was subject to phase variation through slipped-strand mispairing.
      Equivalent results were obtained with strain NCTC11638. We propose that adhesin
      metastability and heterogeneity contributes to bacterial fitness and results in
      some clones having potential for periodic activation and deactivation of
      virulence appropriate for intensity of the host response to infection.

PMID- 15557007
TI  - SMAC/Diablo-dependent apoptosis induced by nonsteroidal antiinflammatory drugs
      (NSAIDs) in colon cancer cells.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) form a paradigm for the
      chemoprevention of cancer, preventing colonic tumor progression in both
      experimental animals and humans. However, the mechanisms underlying the
      antineoplastic effects of NSAIDs are currently unclear. We found that the
      mitochondrial second mitochondrial-derived activator of caspase (SMAC)/direct
      inhibitor of apoptosis protein-binding protein with low pI (Diablo) protein
      translocates into the cytosol during NSAID-induced apoptosis in colon cancer
      cells. When SMAC/Diablo is disrupted by homologous recombination and RNA
      interference in these cells, the NSAID-induced apoptosis is abrogated.
      Biochemical markers of apoptosis, such as caspase activation, cytosolic release
      of cytochrome c and apoptosis-inducing factor, and mitochondrial membrane
      potential change, are accordingly decreased. These results establish that
      SMAC/Diablo is essential for the apoptosis induced by NSAIDs in colon cancer
      cells.

PMID- 15557008
TI  - Chemoreflex control of breathing during wakefulness in healthy men and women.
AB  - This study used a modified CO(2) rebreathing procedure to examine the effect of
      gender on the chemoreflex control of breathing during wakefulness in healthy men
      (n = 14) and women (n = 14). Women were tested in the follicular phase of the
      menstrual cycle. During rebreathing trials, subjects hyperventilated to reduce
      the partial pressure of end-tidal CO(2) (Pet(CO(2))) below 25 Torr and were then
      switched to a rebreathing bag containing a normocapnic hypoxic or hyperoxic gas
      mixture. During the trial, Pet(CO(2)) increased, while O(2) was maintained at a
      constant level. The point at which ventilation began to rise as Pet(CO(2))
      increased was identified as the ventilatory recruitment threshold (VRT).
      Ventilation below the VRT was measured, and the slope of the ventilatory response
      above the VRT was determined. Gender had no effect on the hyperoxic or hypoxic
      VRT for CO(2). Central chemoreflex sensitivity was significantly greater in men
      than women but not after correction for forced vital capacity. Measures of
      peripheral chemoreflex sensitivity were similar between genders. However, the
      slope of the tidal volume (Vt) response to hyperoxic and hypoxic CO(2)
      rebreathing (corrected and uncorrected) was greater in men than women,
      respectively. We conclude that central chemoreflex sensitivity is greater in men
      compared with women as reflected by differences in ventilatory (uncorrected) and
      Vt (corrected and uncorrected) responses to CO(2). However, gender has no
      significant effect on the central chemoreflex VRT for CO(2). The peripheral
      chemoreflex control of breathing during wakefulness is similar between men and
      women.

PMID- 15557009
TI  - Theoretical and empirical derivation of cardiovascular allometric relationships
      in children.
AB  - Basic fluid dynamic principles were used to derive a theoretical model of optimum
      cardiovascular allometry, the relationship between somatic and cardiovascular
      growth. The validity of the predicted models was then tested against the size of
      22 cardiovascular structures measured echocardiographically in 496 normal
      children aged 1 day to 20 yr, including valves, pulmonary arteries, aorta and
      aortic branches, pulmonary veins, and left ventricular volume. Body surface area
      (BSA) was found to be a more important determinant of the size of each of the
      cardiovascular structures than age, height, or weight alone. The observed
      vascular and valvar dimensions were in agreement with values predicted from the
      theoretical models. Vascular and valve diameters related linearly to the square
      root of BSA, whereas valve and vascular areas related to BSA. The relationship
      between left ventricular volume and body size fit a complex model predicted by
      the nonlinear decrease of heart rate with growth. Overall, the relationship
      between cardiac output and body size is the fundamental driving factor in
      cardiovascular allometry.

PMID- 15557010
TI  - Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in
      the diaphragm.
AB  - Prolonged mechanical ventilation (MV) results in diaphragmatic atrophy due, in
      part, to an increase in proteolysis. These experiments tested the hypothesis that
      MV-induced diaphragmatic proteolysis is accompanied by increased expression of
      key components of the ubiquitin-proteasome pathway (UPP). To test this postulate,
      we investigated the effect of prolonged MV on UPP components and determined the
      trypsin-like and peptidylglutamyl peptide hydrolyzing activities of the 20S
      proteasome. Adult Sprague-Dawley rats were assigned to either control or 12-h MV
      groups (n=7/group). MV animals were anesthetized, tracheostomized, and ventilated
      with room air for 12 h. Animals in the control group were acutely anesthetized
      but not exposed to MV. Compared with controls, MV animals demonstrated increased
      diaphragmatic mRNA levels of two ubiquitin ligases, muscle atrophy F-box (+8.3
      fold) and muscle ring finger 1 (+19.0-fold). However, MV did not alter mRNA
      levels of 14-kDa ubiquitin-conjugating enzyme, polyubiquitin, proteasome
      activating complex PA28, or 20S alpha-subunit 7. Protein levels of 14-kDa
      ubiquitin-conjugating enzyme and proteasome-activating complex PA28 were not
      altered following MV, but 20S alpha-subunit 7 levels declined (-17.7%). MV
      increased diaphragmatic trypsin-like activity (+31%) but did not alter
      peptidylglutamyl peptide hydrolyzing activity. Finally, compared with controls,
      MV increased ubiquitin-protein conjugates in both the myofibrillar (+24.9%) and
      cytosolic (+54.7%) fractions of the diaphragm. These results are consistent with
      the hypothesis that prolonged MV increases diaphragmatic levels of key components
      within the UPP and that increases in 20S proteasome activity contribute to MV
      induced diaphragmatic proteolysis and atrophy.

PMID- 15557011
TI  - Geniohyoid muscle properties and myosin heavy chain composition are altered after
      short-term intermittent hypoxic exposure.
AB  - Patients with obstructive sleep apnea (OSA) often exhibit fatigued or inefficient
      upper airway dilator and constrictor muscles; an upper airway dilator, the
      geniohyoid (GH) muscle, is a particular example. Intermittent hypoxia (IH) is a
      frequent concomitant of OSA, and it may trigger muscle fiber composition changes
      that are characteristic of a fatigable nature. We examined effects of short-term
      IH on diaphragmatic and GH muscle fiber composition and fatigue properties by
      exposing 24 rats to alternating 10.3% O(2)-balance N(2) and room air every 480 s
      (240 s duty cycle) for a total duration of 5, 10, 15, 20, or 30 h. Sternohyoid
      fiber composition was also examined. Control animals were exposed to room air on
      the same schedule. Single-fiber analyses showed that GH muscle fiber types
      changed completely from myosin heavy chain (MHC) type 2A to MHC type 2B after 10
      h of exposure, and the conversion was maintained for at least 30 h. Sternohyoid
      muscle fibers showed a delayed transition from MHC type 2A/2B to MHC type 2B. In
      contrast, major fiber types of the diaphragm were not significantly altered. The
      GH muscles showed similar tension-frequency relationships in all groups, but an
      increased fatigability developed, proportional to the duration of IH treatment.
      We conclude that short-term IH exposure alters GH muscle composition and physical
      properties toward more fatigable, fast-twitch types and that it may account for
      the fatigable upper airway fiber types found in sleep-disturbed breathing.

PMID- 15557012
TI  - Thrombin and histamine induce stiffening of alveolar epithelial cells.
AB  - The mechanical properties of alveolar epithelial cells play a central role in
      maintaining the physical integrity of the alveolar epithelium. We studied the
      viscoelastic properties of alveolar epithelial cells (A549) in response to
      thrombin and histamine with optical magnetic twisting cytometry. Ferrimagnetic
      beads coated with Arg-Gly-Asp (RGD)-peptide or acetylated low-density lipoprotein
      were bound to cell surface receptors and subsequently twisted in an oscillatory
      magnetic field (0.1-100 Hz). The cell storage (G') and loss (G'') moduli were
      computed from twisting torque and bead displacement. In measurements with RGD
      coated beads, thrombin (0.5 U/ml) induced a rapid and sustained threefold
      increase in G' and G'' at approximately 100 s after challenge. Histamine (100
      microM) induced a rapid but transient twofold increase in G' and G'' with maximum
      values 60 s after challenge. Posttreatment with cytochalasin D abolished thrombin
      induced cell stiffening. G' increased with frequency following a power law with
      exponent 0.214. G'' increased proportionally to G' up to 10 Hz but showed a
      steeper rise at higher frequencies. Thrombin caused a fall in the power-law
      exponent (0.164). In measurements with acetylated low-density lipoprotein-coated
      beads, minor changes (<20%) were observed in G' and G'' after the addition of
      thrombin and histamine. F-actin staining revealed that thrombin and histamine
      induced a profound reorganization of the actin cytoskeleton at the cell periphery
      and formation of actin bundles. In the mechanically dynamic environment of the
      lung, cell stiffening induced by thrombin and histamine increases centripetal
      tension, which could contribute to alveolar barrier dysfunction.

PMID- 15557013
TI  - Orexin stimulates breathing via medullary and spinal pathways.
AB  - A central neuronal network that regulates respiration may include hypothalamic
      neurons that produce orexin, a peptide that influences sleep and arousal. In
      these experiments, we investigated 1) projections of orexin-containing neurons to
      the pre-Botzinger region of the rostral ventrolateral medulla that regulates
      rhythmic breathing and to phrenic motoneurons that innervate the diaphragm; 2)
      the presence of orexin A receptors in the pre-Botzinger region and in phrenic
      motoneurons; and 3) physiological effects of orexin administered into the pre
      Botzinger region and phrenic nuclei at the C3-C4 levels. We found orexin
      containing fibers within the pre-Botzinger complex. However, only 0.5% of orexin
      containing neurons projected to the pre-Botzinger region, whereas 2.9% of orexin
      containing neurons innervated the phrenic nucleus. Neurons of the pre-Botzinger
      region and phrenic nucleus stained for orexin receptors, and activation of orexin
      receptors by microperfusion of orexin in either site produced a dose-dependent,
      significant (P <0.05) increase in diaphragm electromyographic activity. These
      data indicate that orexin regulates respiratory activity and may have a role in
      the pathophysiology of sleep-related respiratory disorders.

PMID- 15557014
TI  - An expanded latch-bridge model of protein kinase C-mediated smooth muscle
      contraction.
AB  - A thin-filament-regulated latch-bridge model of smooth muscle contraction is
      proposed to integrate thin-filament-based inhibition of actomyosin ATPase
      activity with myosin phosphorylation in the regulation of smooth muscle
      mechanics. The model included two latch-bridge cycles, one of which was identical
      to the four-state model as proposed by Hai and Murphy (Am J Physiol Cell Physiol
      255: C86-C94, 1988), whereas the ultraslow cross-bridge cycle has lower cross
      bridge cycling rates. The model-fitted phorbol ester induced slow contractions at
      constant myosin phosphorylation and predicted steeper dependence of force on
      myosin phosphorylation in phorbol ester-stimulated smooth muscle. By shifting
      cross bridges between the two latch-bridge cycles, the model predicts that a
      smooth muscle cell can either maintain force at extremely low-energy cost or
      change its contractile state rapidly, if necessary. Depending on the fraction of
      cross bridges engaged in the ultraslow latch-bridge cycle, the model predicted
      biphasic kinetics of smooth muscle mechanics and variable steady-state
      dependencies of force and shortening velocity on myosin phosphorylation. These
      results suggest that thin-filament-based regulatory proteins may function as
      tuners of actomyosin ATPase activity, thus allowing a smooth muscle cell to have
      two discrete cross-bridge cycles with different cross-bridge cycling rates.

PMID- 15557015
TI  - Postactivation potentiation influences differently the nonlinear summation of
      contractions in young and elderly adults.
AB  - The force enhancement of a twitch after a maximal conditioning muscle contraction
      [i.e., postactivation potentiation (PAP)] is reduced with aging, but its
      influence on the summation of force in response to repetitive stimulation at
      different frequencies is not known. The purpose of this work was to compare the
      electrically evoked mechanical responses of the tibialis anterior muscle between
      young and elderly adults after a 6-s maximal voluntary contraction (MVC). The
      results showed that, immediately after the conditioning MVC, twitch torque and
      its maximal rate of development and relaxation were significantly enhanced in
      both groups, but the magnitude of potentiation was greater in young (148.0 +/-
      14.2, 123.7 +/- 16.5, and 185.4 +/- 36.5%, respectively) compared with elderly
      adults (87.4 +/- 15.2, 63.8 +/- 9.9, and 62.9 +/- 11.0%, respectively). This age
      related difference in potentiation of the twitch disappeared completely 1 min
      after the conditioning MVC. The potentiation of torque and speed-related
      parameters in response to two- and three-pulse trains, delivered at a constant
      interval of 10 ms (100 Hz), was less than for a single pulse for both groups. In
      young adults, the magnitude of PAP on the successive individual mechanical
      contributions within a train of stimuli declined progressively such that the
      third contribution did not differ significantly from the same contribution before
      the conditioning MVC. In contrast, the second and third contributions did not
      potentiate (P > 0.05) in elderly adults. Although these contributions did
      potentiate significantly at a lower frequency of stimulation (20 Hz) in the two
      groups, the difference in PAP between young and elderly adults still persisted.
      This overall attenuation of potentiation with aging, however, appears to have a
      moderate influence on the decrement of the muscular performance.

PMID- 15557016
TI  - Muscle contraction-blood flow interactions during upright knee extension exercise
      in humans.
AB  - To test for evidence of a muscle pump effect during steady-state upright
      submaximal knee extension exercise, seven male subjects performed seven
      discontinuous, incremental exercise stages (3 min/stage) at 40 contractions/min,
      at work rates ranging to 60-75% peak aerobic work rate. Cardiac cycle-averaged
      muscle blood flow (MBF) responses and contraction-averaged blood flow responses
      were calculated from continuous Doppler sonography of the femoral artery. Net
      contribution of the muscle pump was estimated by the difference between mean
      exercise blood flow (MBFM) and early recovery blood flow (MBFR). MBFM rose in
      proportion with increases in power output with no significant difference between
      the two methods of calculating MBF. For stages 1 and 5, MBFM was greater than
      MBFR; for all others, MBFM was similar to MBFR. For the lighter work rates
      (stages 1-4), there was no significant difference between exercise and early
      recovery mean arterial pressure (MAP). During stages 5-7, MAP was significantly
      higher during exercise and fell significantly early in recovery. From these
      results we conclude that 1) at the lightest work rate, the muscle pump had a net
      positive effect on MBFM, 2) during steady-state moderate exercise (stages 2-4)
      the net effect of rhythmic muscle contraction was neutral (i.e., the impedance
      due to muscle contraction was exactly offset by the potential enhancement during
      relaxation), and 3) at the three higher work rates tested (stages 5-7), any
      enhancement to flow during relaxation was insufficient to fully compensate for
      the contraction-induced impedance to muscle perfusion. This necessitated a higher
      MAP to achieve the MBFM.

PMID- 15557017
TI  - Altered airway responsiveness in CD38-deficient mice.
AB  - Cyclic ADP-ribose (cADPR) mobilizes calcium from intracellular stores and
      contributes to agonist-induced intracellular calcium elevation in airway smooth
      muscle (ASM). In this study we determined the functional role of CD38/cADPR
      signaling in the regulation of airway tone using CD38 deficient (cd38(-/-)) mice.
      The responsiveness to different doses of methacholine, as determined by changes
      in lung resistance and dynamic compliance, was significantly (P < or = 0.05)
      lower in cd38(-/-) mice compared with wild-type controls. To determine the
      mechanism responsible for the reduced responsiveness, we measured the
      intracellular calcium responses to contractile agonists in ASM cells. In ASM
      cells isolated from cd38(-/-) mice, the intracellular calcium responses to
      acetylcholine and endothelin-1 were significantly lower than in controls.
      Pretreatment of ASM cells with a cADPR antagonist resulted in attenuated
      intracellular calcium responses to endothelin-1 in cells isolated from wild-type
      mice, but not in those isolated from the cd38(-/-) mice. Very low cADPR levels
      and no detectable ADP-ribosyl cyclase activity were observed in lung tissue from
      cd38(-/-) mice, suggesting that CD38 is a critical source for cADPR synthesis.
      The results of the present study demonstrate that CD38/cADPR contributes to
      airway smooth muscle tone and responsiveness through its effects on agonist
      induced elevation of intracellular calcium in ASM cells.

PMID- 15557018
TI  - Moraxella catarrhalis--infected alveolar epithelium induced monocyte recruitment
      and oxidative burst.
AB  - The recruitment of monocytes appears to be a crucial factor for inflammatory lung
      disease. Alveolar epithelial cells contribute to monocyte influx into the lung,
      but their impact on monocyte inflammatory capacity is not entirely clear. We thus
      analyzed the modulation of monocyte oxidative burst by A549 and isolated human
      alveolar epithelial cells. Epithelial infection with Moraxella catarrhalis
      induced monocyte adhesion, transepithelial migration, and superoxide generation,
      whereas stimulation with lipopolysaccharide, tumor necrosis factor-alpha,
      interleukin-1beta, or interferon-gamma induced adhesion or transmigration, but
      failed to initiate monocyte burst. The effect of microbial challenge was mimicked
      by phorbol myristate acetate and inhibited by the protein kinase C inhibitor
      bisindoylmaleimide. Furthermore, evidence for a role of platelet-activating
      factor-signaling in monocytes is presented. Monocyte burst was neither induced by
      supernatant nor affected by fixation of A549 cells, excluding the contribution of
      epithelium-derived soluble factors but emphasizing the mandatory role of
      intercellular contact. The employment of blocking antibodies, however, denied a
      role for the adhesion molecules intercellular adhesion molecule-1 and vascular
      cell adhesion molecule-1, or CD11b/CD18 and CD49d/CD29. In essence, infection of
      alveolar epithelial cells with M. catarrhalis might amplify the inflammatory
      capacity of invading monocytes eliciting their superoxide production. The
      epithelial response to this microbial challenge thus clearly differed from that
      to proinflammatory cytokines.

PMID- 15557019
TI  - Interferon-{beta} inhibits bleomycin-induced lung fibrosis by decreasing
      transforming growth factor-{beta} and thrombospondin.
AB  - Pulmonary fibrosis is the result of abnormal processes of repair that occur after
      lung injury. Transforming growth factor (TGF)-beta is a key molecule in the
      progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta
      did not improve survival in patients with idiopathic pulmonary fibrosis, because
      some preclinical studies have suggested that IFN-beta is a potent inhibitor of
      fibrogenesis, beneficial effects of IFN-beta have been expected. We therefore
      attempted to determine effects of IFN-beta and investigated the mechanism of
      action of IFN-beta in bleomycin-induced pulmonary fibrosis. Bleomycin at Day 0
      and IFN-beta for 4 wk were administered intravenously to ICR mice. At 28 d after
      bleomycin injection, histologic and chemical analysis was performed for
      evaluation of effects of IFN-beta. Tissue distribution and amounts of TGF-beta1
      and thrombospondin (TSP)-1/2 were analyzed. IFN-beta attenuated prolylhydroxylase
      activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced
      increase in TGF-beta1 in epithelial cells and extracellular matrix was attenuated
      by IFN-beta. TSP-1/2 was limited in platelets of control mice, but was present in
      foamy cells in fibrotic regions induced by bleomycin. These findings suggest that
      the antifibrotic effect of IFN-beta is inhibition of TGF-beta and its activation
      via decrease in TSP-1/2 in lung tissue and change in location of TSP-1/2 from
      platelets to foamy cells.

PMID- 15557021
TI  - Rapid evolution of muscle fibre number in post-glacial populations of Arctic
      charr Salvelinus alpinus.
AB  - Thingvallavatn, the largest and one of the oldest lakes in Iceland, contains four
      morphs of Arctic charr Salvelinus alpinus. Dwarf benthic (DB), large benthic
      (LB), planktivorous (PL) and piscivorous (PI) morphs can be distinguished and
      differ markedly in head morphology, colouration and maximum fork length
      (FL(max)), reflecting their different resource specialisations within the lake.
      The four morphs in Thingvallavatn are thought to have been isolated for
      approximately 10 000 years, since shortly after the end of the last Ice Age. We
      tested the null hypothesis that the pattern of muscle fibre recruitment was the
      same in all morphs, reflecting their recent diversification. The cross-sectional
      areas of fast and slow muscle fibres were measured at 0.7 FL in 46 DB morphs, 23
      LB morphs, 24 PL morphs and 22 PI morphs, and the ages of the charr were
      estimated using sacculus otoliths. In fish larger than 10 g, the maximum fibre
      diameter scaled with body mass (M(b))(0.18) for both fibre types in all morphs.
      The number of myonuclei per cm fibre length increased with fibre diameter, but
      was similar between morphs. On average, at 60 mum diameter, there were 2264
      nuclei cm(-1) in slow fibres and 1126 nuclei cm(-1) in fast fibres. The absence
      of fibres of diameter 4-10 mum was used to determine the FL at which muscle fibre
      recruitment stopped. Slow fibre number increased with body length in all morphs,
      scaling with M(b)(0.45). In contrast, the recruitment of fast muscle fibres
      continued until a clearly identifiable FL, corresponding to 18-19 cm in the dwarf
      morph, 24-26 cm in the pelagic morph, 32-33 cm in the large benthic morph and 34
      35 cm in the piscivorous morph. The maximum fast fibre number (FN(max)) in the
      dwarf morph (6.97x10(4)) was 56.5% of that found in the LB and PI morphs combined
      (1.23x10(5)) (P<0.001). Muscle fibre recruitment continued until a threshold body
      size and occurred at a range of ages, starting at 4+ years in the DB morph and 7+
      years in the LB and PI morphs. Our null hypothesis was therefore rejected for
      fast muscle and it was concluded that the dwarf condition was associated with a
      reduction in fibre number. We then investigated whether variations in development
      temperature associated with different spawning sites and periods were responsible
      for the observed differences in muscle cellularity between morphs. Embryos from
      the DB, LB and PL morphs were incubated at temperature regimes simulating cold
      subterranean spring-fed sites (2.2-3.2 degrees C) and the general lakebed (4-7
      degrees C). Myogenic progenitor cells (MPCs) were identified using specific
      antibodies to Paired box protein 7 (Pax 7), Forkhead box protein K1-alpha (FoxK1
      alpha), MyoD and Myf-5. The progeny showed no evidence of developmental
      plasticity in the numbers of either MPCs or muscle fibres. Juveniles and adult
      stages of the DB and LB morphs coexist and have a similar diet. We therefore
      conclude that the reduction in FN(max) in the dwarf morph probably has a genetic
      basis and that gene networks regulating myotube production are under high
      selection pressure. To explain these findings we propose that there is an optimal
      fibre size, and hence number, which varies with maximum body size and reflects a
      trade-off between diffusional constraints on fibre diameter and the energy costs
      of maintaining ionic gradients. The predictions of the optimal fibre size
      hypothesis and its consequences for the adaptive evolution of muscle architecture
      in fishes are briefly discussed.

PMID- 15557022
TI  - Echolocation signal structure in the Megachiropteran bat Rousettus aegyptiacus
      Geoffroy 1810.
AB  - Rousettus aegyptiacus Geoffroy 1810 is a member of the only genus of
      Megachiropteran bats to use vocal echolocation, but the structure of its brief,
      click-like signal is poorly described. Although thought to have a simple
      echolocation system compared to that of Microchiroptera, R. aegyptiacus is
      capable of good obstacle avoidance using its impulse sonar. The energy content of
      the signal was at least an order of magnitude smaller than in Microchiropteran
      bats and dolphins (approximately 4 x 10(-8) J m(-2)). Measurement of the
      duration, amplitude and peak frequency demonstrate that the signals of this
      animal are broadly similar in structure and duration to those of dolphins. Gabor
      functions were used to model signals and to estimate signal parameters, and the
      quality of the Gabor function fit to the early part of the signal demonstrates
      that the echolocation signals of R. aegyptiacus match the minimum spectral spread
      for their duration and amplitude and are thus well matched to its best hearing
      sensitivity. However, the low energy content of the signals and short duration
      should make returning echoes difficult to detect. The performance of R.
      aegyptiacus in obstacle avoidance experiments using echolocation therefore
      remains something of a conundrum.

PMID- 15557023
TI  - Floral scents induce recall of navigational and visual memories in honeybees.
AB  - During foraging flights, honeybees learn visual and chemical cues associated with
      a food source. We investigated whether learned olfactory cues can trigger visual
      and navigational memories in honeybees that assist them in navigating back to a
      known food source. In a series of experiments, marked bees were trained to forage
      at one or more sugar water feeders, placed at different outdoor locations and
      carrying different scents or colours. We then tested the ability of these bees to
      recall the locations (or colours) of these food sites and to fly to them, when
      the training scents were blown into the hive, and the scents and food at the
      feeders were removed. The results show that (1) bees, trained to a single-scented
      feeder at a given location, can be induced to fly to the same location by blowing
      the scent into the hive; (2) bees, trained to two feeders, each placed at a
      different location and carrying a different scent, can be induced to fly to
      either location by blowing the appropriate scent into the hive; and (3) bees,
      trained to two feeders, each decorated with a different colour and carrying a
      different scent, can be induced to find a feeder of either colour by blowing the
      appropriate scent into the hive. Thus, familiar scents can trigger navigational
      and visual memories in experienced bees. Our findings suggest that the odour and
      taste of the nectar samples that are distributed by successful foragers on
      returning to the hive, may trigger recall of navigational memories associated
      with the food site in experienced recruits and, thus, facilitate their navigation
      back to the site.

PMID- 15557024
TI  - Hummingbirds arrest their kidneys at night: diel variation in glomerular
      filtration rate in Selasphorus platycercus.
AB  - Small nectarivorous vertebrates face a quandary. When feeding, they must
      eliminate prodigious quantities of water; however, when they are not feeding,
      they are susceptible to dehydration. We examined the role of the kidney in the
      resolution of this osmoregulatory dilemma. Broad-tailed hummingbirds (Selasphorus
      platycercus) displayed diurnal variation in glomerular filtration rate (GFR).
      During the morning, midday and evening, GFRs were 0.9+/-0.6, 1.8+/-0.4 and 2.3+/
      0.5 ml h(-1), respectively. At midday, GFR increased linearly with increased
      water intake. During the evening, hummingbirds decreased renal fractional water
      reabsorption linearly with increased water intake. Broad-tailed hummingbirds
      appeared to cease GFR at night (-0.1+/-0.2 ml h(-1)) and decreased GFR in
      response to short-term ( approximately 1.5 h) water deprivation. GFR seems to be
      very responsive to water deprivation in hummingbirds. Although hummingbirds and
      other nectarivorous birds can consume astounding amounts of water, a
      phylogenetically explicit allometric analysis revealed that their diurnal GFRs
      are not different from the expectation based on body mass.

PMID- 15557025
TI  - Crater landscape: two-dimensional oxygen gradients in the circulatory system of
      the microcrustacean Daphnia magna.
AB  - Oxygen transport processes in millimetre-sized animals can be very complex,
      because oxygen molecules do not exclusively follow the pathway predetermined by
      the circulating fluid but may also simultaneously move from the respiratory
      surfaces to the tissues along different paths by diffusion. The present study
      made use of the oxygen-sensitive phosphorescence probe Oxyphor R2 to analyze the
      internal oxygen pathway in the transparent microcrustacean Daphnia magna. Oxyphor
      R2 was injected into the circulatory system and the distribution of oxygen
      partial pressure (P(O(2))) in the haemolymph was measured by phosphorescence
      lifetime imaging in the P(O(2)) range 0-6 kPa (0-30% air saturation). There were
      substantial differences in the shape of the two-dimensional P(O(2)) profiles
      depending on the concentration of haemoglobin (Hb) in the haemolymph. A steep
      global gradient, from posterior to anterior, occurred in animals with low
      concentrations of Hb (90-167 micromol l(-1) haem). In contrast, animals with a
      five- to sixfold higher concentration of Hb showed flat internal P(O(2))
      gradients which, however, were only present under reduced ambient oxygen tensions
      (P(O(2)amb)=3-1 kPa), when Hb was maximally involved in oxygen transport. Under
      these conditions, the presence of Hb at high concentrations stabilized the
      unloading P(O(2)) in the central body to 0.9-0.4 kPa. Independent of Hb
      concentration and body size, the loading P(O(2)) was always 0.5 kPa below the
      P(O(2)amb). From these P(O(2)) profiles, it was possible (i) to follow the track
      of oxygen within the animal, and (ii) to visualize the shift from a diffusion
      dominated to a convection-dominated transport as a result of increased Hb
      concentration.

PMID- 15557026
TI  - Partial link between the seasonal acquisition of cold-tolerance and desiccation
      resistance in the goldenrod gall fly Eurosta solidaginis (Diptera: Tephritidae).
AB  - Possible links between seasonal increases in cold-tolerance and desiccation
      resistance were examined in field-collected larvae of the goldenrod gall fly,
      Eurosta solidaginis. From 20 September to 30 October 2001, larvae exhibited a
      gradual increase in cold-tolerance culminating in 100% survival of freezing at 
      20 degrees C for 24 h. The increase in cold-tolerance was probably due to a
      concomitant increase in cryoprotectants as measured by hemolymph osmolality (488
      695 mOsmol kg(-1)). In contrast to the gradual increase in cold-tolerance, larvae
      exhibited two distinct phases of reduced rates of water loss. The first phase was
      an abrupt sixfold decrease to 0.57 microg mm(-2) h(-1) between 3 and 16 October.
      The first phase of reduced rates of water loss was not correlated with changes in
      cold-tolerance; nor was it correlated with hemolymph osmolality and body water
      content, which remained constant throughout the study. The reduction in rates of
      water loss during the first phase were probably the result of decreased
      respiratory water loss as the larvae entered diapause, and possibly reduced
      cuticular water loss as larvae increased the amount of their cuticular
      hydrocarbons. Interestingly, the first phase of reduced water loss was associated
      with, and may have been cued by, a reduction in the water potential of the gall
      tissues surrounding the larvae. The second phase was a more subtle fourfold
      reduction in rates of water loss occurring between 16 October and 11 December. In
      contrast to the first phase, the second phase of increased desiccation resistance
      correlated closely with increases in hemolymph osmolality (568-870 mOsmol kg(
      1)). The correlation between seasonal increases in hemolymph osmolality and
      reduction in rates of water loss may represent a link between desiccation
      resistance and cold-tolerance in this species.

PMID- 15557027
TI  - How a low tissue O2 strategy could be conserved in early crustaceans: the example
      of the podocopid ostracods.
AB  - An adaptation strategy whereby O(2) partial pressure, P(O(2)), in the tissues is
      maintained within a low, narrow range of 1-3 kPa, largely independent of the
      inspired P(O(2)), has been reported in water- and air-breathing poikilotherms and
      in homeotherms. Based on the postulate that this basic cellular mechanism has
      been established since the early stages of evolution, it has been hypothesized
      that it could be the consequence of an early adaptation strategy to maintain
      cellular oxygenation within the same low and primitive range. To test this
      hypothesis we studied the basic mechanisms of oxygen regulation in podocopid
      ostracods, minute crustaceans that have existed on earth for at least 500 million
      years. Podocopids lack any regulatory mechanism for adapting their ventilation to
      cope with changes in water oxygenation, and instead adjust their tissue
      oxygenation status by migrating through the O(2) gradient to sediment layers
      where the P(O(2)) of the water is 3-5 kPa. Experimental manipulation of the O(2)
      profile induced their vertical migration to follow this precise water P(O(2)) and
      demonstrates the existence of a regulation strategy. This strategy must be
      associated with the lower P(O(2)) values within the animal's carapace valves,
      showing that podocopids can actively regulate their tissue P(O(2)) at constant
      but even lower values than the water. In conclusion, the low tissue P(O(2))
      strategy could have existed in early crustaceans and, by extension, in early
      animals.

PMID- 15557028
TI  - Stabilization and mobility of the head and trunk in vervet monkeys (Cercopithecus
      aethiops) during treadmill walks and gallops.
AB  - The brain requires internal or external reference frames to determine body
      orientation in space. These frames may change, however, to meet changing
      conditions. During quadrupedal overground locomotion by monkeys, the head rotates
      on a stabilized trunk during walking, but the trunk rotates on a stabilized head
      during galloping. Do the same movement patterns occur during in-place locomotion?
      Head and trunk pitch rotations were measured, and yaw and roll rotations
      estimated from cine films of three adult vervet monkeys (Cercopithecus aethiops
      L. 1758) walking and galloping quadrupedally on a treadmill. Head and trunk
      rotational patterns during treadmill walks were comparable to the patterns found
      during overground walks. The rotational velocities of these segments during both
      treadmill walks and gallops were also comparable to the velocities found during
      natural locomotion. By contrast, whereas head and trunk rotational patterns
      during treadmill gallops did occur that were comparable to the patterns practiced
      during overground gallops, a significantly different pattern involving large and
      simultaneous head and trunk rotations was more commonly observed. Simultaneous
      head and trunk rotations may be possible during treadmill gallops because the
      fixed visual surround is providing an adequate spatial reference frame.
      Alternatively, or in addition to this visual information, a re-weighting in other
      sensory modalities may be occurring. Specifically, the vestibular inputs used
      during overground locomotion to reference gravity or a gravity-derived vector may
      become less important than proprioceptive inputs that are using the treadmill
      belt surface as a reference. Regardless, the spatial reference frame being used,
      blinks that occur at specific times during the largest head yaw rotations may be
      necessary to avoid the initiation of unwanted and potentially destabilizing
      lateral sway brought on by sudden increases in optic flow velocity.

PMID- 15557029
TI  - Peptidergic innervation of the vasoconstrictor muscle of the abdominal aorta in
      Aplysia kurodai.
AB  - The arterial system of the marine mollusc Aplysia consists of three major
      arteries. One of them, the abdominal aorta, has a sphincter (the vasoconstrictor
      muscle) at the base of the artery. Contraction of this muscle reduces the blood
      flow into the abdominal aorta, thereby, playing a role in the regulation of the
      blood distribution in Aplysia. Here, we show the contractility of the
      vasoconstrictor muscle is modulated by three types of endogenous peptides,
      Aplysia mytilus inhibitory peptide-related peptides (AMRP), enterin and
      NdWFamide. Immunohistochemistry showed that putative neuronal processes
      containing the three peptides exist in the vasoconstrictor muscle. Enterin
      inhibited the muscle contraction elicited by the nerve stimulation or the
      application of a putative excitatory transmitter, acetylcholine (ACh). Enterin
      hyperpolarized the resting potential of the muscle and decreased the amplitude of
      the excitatory junction potential (EJP). AMRP also inhibited the nerve-evoked
      contraction although its action on the ACh-induced contraction was variable. AMRP
      also reduced the size of EJP, but had no effect on the resting potential of the
      muscle. NdWFamide enhanced the nerve-evoked contraction but not the ACh-induced
      contraction. NdWFamide augmented EJP without affecting the resting potential of
      the muscle. These results suggest that AMRP, enterin and NdWFamide are endogenous
      modulators of the contractile activity of the vasoconstrictor muscle, and that
      the peptidergic innervations of this muscle contribute to fine tuning of the
      blood distribution in Aplysia.

PMID- 15557030
TI  - Adenosinergic and cholinergic control mechanisms during hypoxia in the epaulette
      shark (Hemiscyllium ocellatum), with emphasis on branchial circulation.
AB  - Coral reef platforms may become hypoxic at night during low tide. One animal in
      that habitat, the epaulette shark (Hemiscyllium ocellatum), survives hours of
      severe hypoxia and at least one hour of anoxia. Here, we examine the branchial
      effects of severe hypoxia (<0.3 mg oxygen l(-1) for 20 min in anaesthetized
      epaulette shark), by measuring ventral and dorsal aortic blood pressure (P(VA)
      and P(DA)), heart rate (fh), and observing gill microcirculation using epi
      illumination microscopy. Hypoxia induced a flow of blood in two parallel blood
      vessels, termed longitudinal vessels, in the outer borders of the free tip of the
      gill filament. Hypoxia also induced significant falls in fh, P(VA) and P(DA), and
      a biphasic change in ventilation frequency (increase followed by decrease).
      Adenosine injection (1 micromol kg(-1)) also initiated blood flow in the
      longitudinal vessels, in addition to significant drops in P(VA), P(DA) and fh,
      and a biphasic response in ventilation frequency (decrease followed by increase)
      indicating that adenosine influences ventilation. Aminophylline (10 mg kg(-1)),
      an A(1) and A(2) adenosine receptor antagonist, blocked the effects of adenosine
      injection, and also significantly reduced blood flow in the longitudinal vessels
      during hypoxia. In the second part of the study, we examined the cholinergic
      influence on the cardiovascular circulation during severe hypoxia (<0.3 mg l(-1))
      using antagonists against muscarinic (atropine 2 mg kg(-1)) and nicotinic
      (tubocurarine 5 mg kg(-1)) receptors. Injection of acetylcholine (ACh; 1 micromol
      kg(-1)) into the ventral aorta caused a marked fall in fh, a large increase in
      P(VA), but small changes in P(DA) (suggesting increased R(gill)). Atropine was
      able to inhibit the branchial vascular responses to ACh but not the hypoxic
      bradycardia, suggesting the presence of muscarinic receptors on the heart and
      gill vasculature, and that the hypoxia induced bradycardia is of non-cholinergic
      origin. The results suggest that adenosine mediates increases in the arterio
      venous circulation in the gill during hypoxia. This may serve to increase blood
      supply to heart and gill tissue.

PMID- 15557031
TI  - The hyperoxic switch: assessing respiratory water loss rates in tracheate
      arthropods with continuous gas exchange.
AB  - Partitioning the relative contributions of cuticular and respiratory water loss
      in a tracheate arthropod is relatively easy if it undergoes discontinuous gas
      exchange cycles or DGCs, leaving its rate of cuticular water loss in primary
      evidence while its spiracles are closed. Many arthropods are not so obliging and
      emit CO(2) continuously, making cuticular and respiratory water losses difficult
      or impossible to partition. We report here that by switching ambient air from 21
      to 100% O(2), marked spiracular constriction takes place, causing a transient but
      substantial - up to 90% - reduction in CO(2) output. A reduction in water loss
      rate occurs at the same time. Using this approach, we investigated respiratory
      water loss in Drosophila melanogaster and in two ant species, Forelius mccooki
      and Pogonomyrmex californicus. Our results - respiratory water loss estimates of
      23%, 7.6% and 5.6% of total water loss rates, respectively - are reasonable in
      light of literature estimates, and suggest that the 'hyperoxic switch' may allow
      straightforward estimation of respiratory water loss rates in arthropods lacking
      discontinuous gas exchange. In P. californicus, which we were able to measure
      with and without a DGC, presence or absence of a DGC did not affect respiratory
      vs total water loss rates.

PMID- 15557032
TI  - Metamorphosis in Xenopus laevis is not associated with large-scale nuclear DNA
      content variation.
AB  - Amphibian metamorphosis is a complex process that has been speculated to involve
      DNA amplification and chromatin rearrangement. While recent studies have
      concentrated on chromatin rearrangement, only a few studies have dealt with
      variation in the amount of DNA during amphibian metamorphosis. In this study,
      nuclei were isolated from Xenopus laevis at various developmental stages. The
      nuclei were examined in both an unfixed state and a fixed state. The nuclei were
      stained with propidium iodide and analyzed by flow cytometry to determine their
      fluorescence intensity. The unfixed nuclei had higher fluorescence variation
      compared with the fixed nuclei. This increase in variation appeared due to the
      presence of nuclei of variable fluorescence intensity within the unfixed nuclei.
      Upon optimum fixation, which has been speculated to result in more homogeneous
      chromatin conformation and to reduce staining artifacts, the nuclei were observed
      to have less fluorescence intensity variation. The differential fluorescence
      observed in this study is consistent with the hypothesis that large-scale intra
      individual DNA variation is not associated with amphibian metamorphosis.

PMID- 15557033
TI  - Bacterial lipopolysaccharide (LPS) modulates corticotropin-releasing hormone
      (CRH) content and release in the brain of juvenile and adult tilapia (Oreochromis
      mossambicus; Teleostei).
AB  - Although immune endocrine interactions in teleost fish have been shown to involve
      adrenocorticotropin hormone (ACTH) and cortisol, the involvement of corticotropin
      releasing hormone (CRH) has not been demonstrated. The present study investigates
      whether treatment with bacterial endotoxin (lipopolysaccharide, LPS) modulates
      brain CRH contents or in vitro CRH release in tilapia (Oreochromis mossambicus).
      10 days LPS (Escherichia coli) exposure of juvenile tilapia (4.5 weeks post
      hatch) via the ambient water increased brain CRH and alpha-MSH content, whereas
      cortisol contents were not increased. This indicates that the elevation of brain
      CRH levels were not secondary to activation of HPI-axis. Adult tilapia were
      treated for 6 days with LPS (intraperitoneally) and were sampled before and after
      24 h of confinement. Overall LPS pre-treatment modified the reaction of tilapia
      to the additional stressor of 24 h confinement, as interactions between LPS
      treatment and confinement were observed at the level of the hypothalamus
      (diencephalic CRH content), the pituitary (CRH and alpha-MSH content) and in
      plasma glucose levels. In vitro, LPS pre-treatment abolished CRH release from
      telencephalic tissues induced by norepinephrine, one of the CRH secretagogues
      released during stress in vivo. This effect might be a mechanism of action
      through which LPS in vivo abolished the up-regulation of telencephalic CRH
      induced by confinement stress. Our results provide evidence that the role of CRH
      in immune-endocrine interactions is a phylogenetically old mechanism, and we here
      demonstrate that LPS molecules are able to locally modulate CRH release in the
      central nervous system.

PMID- 15557034
TI  - Dummies.

PMID- 15557035
TI  - Infants bed-sharing with mothers.

PMID- 15557036
TI  - Perception of death.

PMID- 15557037
TI  - Doctors in the movies.

PMID- 15557038
TI  - How to assess your specialist registrar.

PMID- 15557039
TI  - Hindu birth customs.

PMID- 15557040
TI  - A drug utilisation study of antidepressants in children and adolescents using the
      General Practice Research Database.
AB  - AIMS: To characterise prescribing patterns of antidepressants (ATDs) to children
      and adolescents aged < or =18 years in the UK. METHODS: Subjects issued at least
      one ATD prescription between 1 January 1992 and 31 December 2001 were identified
      from the UK General Practice Research Database. Prescribing patterns, annual
      prevalence, morbidity patterns, and time to discontinuation of ATD use were
      identified. RESULTS: A total of 24,976 subjects received 93,091 prescriptions;
      51,868 (55.7%), 38,429 (41.3%), and 2708 (2.9%) prescriptions were for tricyclic
      antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and
      other ATDs respectively. ATD prevalence increased 1.7-fold from 1992 to 2001. TCA
      prevalence decreased by 30% from 3.6 to 2.5 per 1,000; SSRI prevalence increased
      10 times from 0.5 to 4.6 per 1,000. In new ATD users aged < or =10 years, the
      most common diagnosis associated with TCA use was nocturnal enuresis (75.1%); in
      those aged > or =15 years, it was depression (45.8%). Depression was also
      associated with SSRI use (69.0%). For new users with depression, the median
      treatment durations for TCAs and SSRIs were 30 and 58 days respectively. TCA
      users were more likely to terminate treatment than SSRI users (TCAs v fluoxetine:
      1.40, 95% CI 1.32 to 1.47; non-fluoxetine SSRIs v fluoxetine: 1.01, 95% CI 0.96
      to 1.07). CONCLUSIONS: SSRIs have gained popularity for the treatment of
      depression compared with TCAs. TCAs are still used despite their lack of efficacy
      in prepubertal depression and their moderate effect in adolescents. However, >50%
      of subjects discontinue treatment after two months, with TCA users stopping
      earlier than SSRI users.

PMID- 15557041
TI  - Could nursery rhymes cause violent behaviour? A comparison with television
      viewing.
AB  - AIMS: To assess the rates of violence in nursery rhymes compared to pre-watershed
      television viewing. METHODS: Data regarding television viewing habits, and the
      amount of violence on British television, were obtained from Ofcom. A compilation
      of nursery rhymes was examined for episodes of violence by three of the
      researchers. Each nursery rhyme was analysed by number and type of episode. They
      were then recited to the fourth researcher whose reactions were scrutinised.
      RESULTS: There were 1045 violent scenes on pre-watershed television over two
      weeks, of which 61% showed the act and the result; 51% of programmes contained
      violence. The 25 nursery rhymes had 20 episodes of violence, with 41% of rhymes
      being violent in some way; 30% mentioned the act and the result, with 50% only
      the act. Episodes of law breaking and animal abuse were also identified.
      Television has 4.8 violent scenes per hour and nursery rhymes have 52.2 violent
      scenes per hour. Analysis of the reactions of the fourth researcher were
      inconclusive. CONCLUSIONS: Although we do not advocate exposure for anyone to
      violent scenes or stimuli, childhood violence is not a new phenomenon. Whether
      visual violence and imagined violence have the same effect is likely to depend on
      the age of the child and the effectiveness of the storyteller. Re-interpretation
      of the ancient problem of childhood and youth violence through modern eyes is
      difficult, and laying the blame solely on television viewing is simplistic and
      may divert attention from vastly more complex societal problems.

PMID- 15557042
TI  - The prevalence and characteristics associated with parent-infant bed-sharing in
      England.
AB  - AIMS: To investigate the characteristics of parent-infant bed-sharing prevalence
      in England. METHODS: Data on night-time sleeping practices from a two year,
      local, longitudinal study and a three-year, national, cross-sectional study were
      obtained. A total of 261 infants in North Tees were followed up at 1 and 3 months
      of age, as were 1095 infants aged 1 week to 1 year from five English health
      regions. RESULTS: Data from both studies found that almost half of all neonates
      bed-shared at some time with their parents (local = 47%, 95% CI 41 to 54;
      national = 46%, 95% CI 34 to 58), and on any one night in the first month over a
      quarter of parents slept with their baby (local = 27%, 95% CI 22 to 33; national
      = 30%, 95% CI 20 to 42). Bed-sharing was not related to younger mothers, single
      mothers, or larger families, and was not more common in the colder months, at
      weekends, or among the more socially deprived families; in fact bed-sharing was
      more common among the least deprived in the first months of life. Breast feeding
      was strongly associated with bed-sharing, both at birth and at 3 months. Bed
      sharing prevalence was uniform with infant age from 3 to 12 months; on any one
      night over a fifth of parents (national = 21%, 95% CI 18 to 24) slept with their
      infants. CONCLUSION: Bed-sharing is a relatively common practice in England, not
      specific to class, but strongly related to breast feeding.

PMID- 15557043
TI  - Bed-sharing and the infant's thermal environment in the home setting.
AB  - AIMS: To study bed-sharing and cot-sleeping infants in the natural setting of
      their own home in order to identify differences in the thermal characteristics of
      the two sleep situations and their potential hazards. METHODS: Forty routine bed
      sharing infants and 40 routine cot-sleeping infants aged 5-27 weeks were
      individually matched between groups for age and season. Overnight video and
      physiological data of bed-share infants and cot-sleeping infants were recorded in
      the infants' own homes including rectal, shin, and ambient temperature. RESULTS:
      The mean rectal temperature two hours after sleep onset for bed-share infants was
      36.79 degrees C and for cot-sleeping infants, 36.75 degrees C (difference 0.05
      degrees C, 95% CI -0.03 to 0.14). The rate of change thereafter was higher in the
      bed-share group than in the cot group (0.04 degrees C v 0.03 degrees C/h,
      difference 0.01, 0.00 to 0.02). Bed-share infants had a higher shin temperature
      at two hours (35.43 v 34.60 degrees C, difference 0.83, 0.18 to 1.49) and a
      higher rate of change (0.04 v -0.10 degrees C/h, difference 0.13, 0.08 to 0.19).
      Bed-sharing infants had more bedding. Face covering events were more common and
      bed-share infants woke and fed more frequently than cot infants (mean wake
      times/night: 4.6 v 2.5). CONCLUSIONS: Bed-share infants experience warmer thermal
      conditions than those of cot-sleeping infants, but are able to maintain adequate
      thermoregulation to maintain a normal core temperature.

PMID- 15557044
TI  - Using children as standardised patients for assessing clinical competence in
      paediatrics.
AB  - BACKGROUND: Standardised patients (SPs) have been widely used to assess
      physicians' clinical competence. However, in paediatrics, the use of children in
      such a way has long been questioned with regard to ethics and the examination
      quality (in terms of validity, reliability, and feasibility). AIMS: To summarise
      the current state of the use of child SPs, and to highlight the difficulties
      inherent in the use of children for this purpose. METHODS: Nineteen articles
      dealing with the use of child SPs for clinical assessment were reviewed. RESULTS:
      Child SPs, ranging in age from infancy to adolescence, were present in varied
      proportions of paediatric objective structured clinical examination stations (12
      27%). In most of these reports, there were several children with cases who could
      substitute for one another. Child SPs successfully portrayed various roles,
      although only older children had to learn a scenario. In general, clinical
      examinations using child SPs were found to be valid and generated reliable
      scores. Child SPs also provided effective feedback. The experience tended to be
      considered negative for younger children but was quite positive for a number of
      older children. The use of young SPs should be avoided for ethical reasons, and
      the use of child SPs should be limited to assessments that cannot be
      satisfactorily measured by other methods. CONCLUSION: Through meticulous
      attention to detail and careful planning, a clinical examination using children
      as SPs can be practical, valid, and reliable.

PMID- 15557045
TI  - Breast feeding, bottle feeding, and non-nutritive sucking; effects on occlusion
      in deciduous dentition.
AB  - AIMS: To assess the effect of the type of feeding and non-nutritive sucking
      activity on occlusion in deciduous dentition. METHODS: Retrospective study of
      1130 preschool children (3-5 years of age) who had detailed infant feeding and
      non-nutritive sucking activity history collected by a structured questionnaire.
      They all had an oral examination by a dentist, blinded to different variables
      evaluated. RESULTS: Non-nutritive sucking activity has a substantial effect on
      altered occlusion, while the effect of bottle feeding is less marked. The type of
      feeding did not have an effect on open bite, which was associated (89% of
      children with open bite) with non-nutritive sucking. Posterior cross-bite was
      more frequent in bottle fed children and in those with non-nutritive sucking
      activity. The percentage of cross-bite was lower in breast fed children with non
      nutritive sucking activity (5%) than in bottle fed children with non-nutritive
      sucking activity (13%). CONCLUSIONS: Data show that non-nutritive sucking
      activity rather than the type of feeding in the first months of life is the main
      risk factor for development of altered occlusion and open bite in deciduous
      dentition. Children with non-nutritive sucking activity and being bottle fed had
      more than double the risk of posterior cross-bite. Breast feeding seems to have a
      protective effect on development of posterior cross-bite in deciduous dentition.

PMID- 15557046
TI  - Health related quality of life in disorders of defecation: the Defecation
      Disorder List.
AB  - BACKGROUND: Constipation and encopresis frequently cause problems with respect to
      emotional wellbeing, and social and family life. Instruments to measure Health
      Related Quality of Life (HRQoL) in these disorders are not available. METHODS: A
      disease specific HRQoL instrument, the "Defecation Disorder List" (DDL) for
      children with constipation or functional non-retentive faecal soiling (FNRFS) was
      developed using accepted guidelines. For each phase of the process, different
      samples of patients were used. The final phase of development included 27
      children. Reliability was assessed in two ways: internal consistency of domains
      with Cronbach's alpha, and test-retest reliability with intra-class correlation
      coefficients (ICC). To assess validity, comparable items and domains were
      correlated with Tacqol, a generic HRQoL instrument for children (TNO-AZL).
      RESULTS: In the final phase of the development, 27 children completed the
      instrument. It consisted of 37 items in four domains. The response rate was 96%.
      Reliability was good for all domains, with Cronbach's alpha values ranging from
      0.61 to 0.76. Measures of test-retest stability were good for all four domains
      with ICCs ranging from 0.82 to 0.92. Validity based on comparison with the Tacqol
      instrument was moderate. CONCLUSION: The DDL is promising as a measure of HRQoL
      in childhood defecation disorders.

PMID- 15557047
TI  - An audit of paediatric audits.
AB  - An audit of audits at a children's hospital over a six year period showed that
      27.8% fulfilled the criteria for a full audit and 22.2% were re-audited. It is
      recommended that newcomers to audit are given training on audit methodology and
      that all audit departments should audit their audits annually.

PMID- 15557048
TI  - Ten puffs too many.

PMID- 15557049
TI  - Who is the piglet used in research on newborn and preterm infants?

PMID- 15557050
TI  - Increased prescribing trends of paediatric psychotropic medications.
AB  - Psychotropic medication use by children in the USA has increased. We used the IMS
      MIDAS Prescribing Insights to examine prescribing trends in nine countries
      between the years 2000 and 2002. Trends in seven countries rose significantly
      from year 2000 to 2002; the UK had the highest increase (68%).

PMID- 15557051
TI  - Botulinum toxin for cerebral palsy; where are we now?
AB  - In this article, the evidence base for botulinum-A treatment acquired in recent
      years is outlined, and the practicalities involved in providing this service are
      described. Botulinum-A is relatively new, and possible improvements for the
      future are considered.

PMID- 15557053
TI  - The epidemiology of subacute sclerosing panencephalitis in England and Wales 1990
      2002.
AB  - AIM: To assess the impact of measles/mumps/rubella (MMR) vaccine on the
      epidemiology of subacute sclerosing panencephalitis (SSPE) in England and Wales.
      METHODS: Cases of SSPE resident in England and Wales with onset between 1990 and
      2002 were reviewed. RESULTS: A total of 47 cases were identified, 31 male and 16
      female. There was an average annual decline of 14% in SSPE onset over the period,
      consistent with the decline in notified measles over the last 20 years. A history
      of measles was present in 35 (median age 1.3 years), the most recent recorded
      date being 1994; the interval from measles to onset of SSPE ranged from 2.7 to
      23.4 years. Four children with a history of receipt of a measles containing
      vaccine were reported not to have had measles; two of these cases had a brain
      biopsy, and nucleotide sequence data confirmed wild measles infection. Brain
      biopsy specimens from a further three cases with a history of measles, of whom
      two had also had a history of vaccination, showed wild-type strain. CONCLUSION:
      The prevention of endemic circulation of measles virus in England and Wales
      through the high coverage achieved with MMR vaccine, together with the
      measles/rubella vaccination campaign of 1994, has resulted in the near
      elimination of SSPE. However, the recent decline in MMR vaccine coverage, with
      the associated increase in localised measles outbreaks and cases in young
      infants, is of concern. It underlines the importance of maintaining high vaccine
      coverage in order to protect indirectly those most vulnerable to SSPE, namely
      infants too young to be vaccinated.

PMID- 15557052
TI  - Acquired non-type 1 diabetes in childhood: subtypes, diagnosis, and management.
AB  - Over the past 30 years it has become apparent that not all diabetes presenting in
      childhood is autoimmune type 1. Increasingly type 2 diabetes, maturity onset
      diabetes of the young, iatrogenic diabetes, and rare syndromic forms of diabetes
      such as Wolfram's syndrome have been identified in children. This review is aimed
      at the general paediatrician looking after children with diabetes, and aims to
      provide an algorithm for assessment, investigation, and suggested management for
      the newly diagnosed child with suspected non-type 1 diabetes. This article will
      also be relevant to the child with atypical diabetes-that is, on low insulin
      doses outside the honeymoon period.

PMID- 15557054
TI  - Early Helicobacter pylori colonisation: the association with growth faltering in
      The Gambia.
AB  - BACKGROUND: Helicobacter pylori is one of the commonest causes of chronic
      infection of mankind, yet the natural history of acute infection is poorly
      understood. Some studies suggest that gastric colonisation with H pylori is
      associated with suboptimal nutrition and growth in childhood. AIMS: To describe
      the clinical features of early H pylori colonisation and assess its role in the
      development of infant malnutrition and growth faltering. METHODS: Two consecutive
      prospective longitudinal cohort studies were conducted at the Medical Research
      Council Laboratories in a rural community in The Gambia, West Africa. The first
      birth cohort of 125 infants was followed by a second of 65 children from the same
      community. H pylori colonisation was detected by sequential 13C urea breath
      tests, and infant growth was monitored by serial measurements. RESULTS: Children
      with early H pylori colonisation became significantly lighter, shorter, and
      thinner than their peers in late infancy. The association was found in both
      cohorts. No socioeconomic or demographic confounding variables were identified to
      explain this, and the weight deficit was no longer detectable when the children
      were aged 5-8 years. CONCLUSIONS: Results suggest that H pylori colonisation in
      early infancy predisposes to the development of malnutrition and growth
      faltering, although the effect did not persist into later childhood.

PMID- 15557055
TI  - Pulmonary and systemic bacterial co-infections in severe RSV bronchiolitis.
AB  - In 127 infants admitted to intensive care for RSV bronchiolitis, concomitant
      bacterial sepsis was a rare event. However, in the subgroup of intubated patients
      the incidence of bacterial pneumonia was 43.9% (95% CI 31.0-56.8%), half
      community acquired and half nosocomial. As clinical signs are not helpful in
      identifying these patients, tracheal aspirates have to be investigated
      microbiologically on a routine basis in order to start antibiotics in time.

PMID- 15557056
TI  - Trends in asthma hospitalisation: is this related to prevention inhaler usage?

PMID- 15557057
TI  - Familial dysalbuminaemic hyperthyroxinaemia, a thyroid trap.

PMID- 15557058
TI  - The bleeding child; is it NAI?
AB  - As a paediatric haematologist, the question of whether a child has been abused or
      whether they might have a bleeding diathesis is a question that I am regularly
      asked. When I first became a consultant, I would often find that not enough
      information was available; for example, incomplete histories had been taken or
      investigations were incomplete and difficult to interpret. This inevitably led to
      delays in confirming the cause of the bleeding and meant that if parents or
      carers contested a diagnosis of abuse, excluding a bleeding disorder was
      extremely difficult. I was also aware that carers of several of my patients with
      haemophilia or other bleeding disorders had initially been under suspicion of
      abuse, most usually at the time of the first few presentations. By highlighting
      important questions in history taking, having a specific haematological screen
      for children being investigated for bleeding in the context of non-accidental
      injury, and encouraging discussion of abnormal results with a haematologist,
      these difficulties can, for the most part, be avoided.

PMID- 15557059
TI  - Interventional cardiac catheterisation in congenital heart disease.
AB  - As a result of recent technological advances, more types of congenital heart
      disease are amenable to treatment in the cardiac catheter laboratory than ever
      before.1 Improved imaging techniques allow for better selection of patients, and
      the development of a wide range of devices specifically for use in children means
      that many patients can avoid surgery altogether, while those with complex
      congenital heart disease may require fewer or less complex surgical procedures.2
      This allows for a quicker recovery and a shorter hospital stay, and gives many
      patients an improved quality of life in the short to medium term. However, the
      long term outcome for many of the newer forms of intervention is still unknown.

PMID- 15557061
TI  - Mosaic Down's syndrome prevalence in a complete population study.

PMID- 15557062
TI  - Hypothermia following fever.

PMID- 15557063
TI  - Audit activity of trainees in the West of Scotland.

PMID- 15557064
TI  - Research, more hassle than it's worth? A personal viewpoint.

PMID- 15557065
TI  - Aspirin, Reye syndrome, Kawasaki disease, and allergies; a reconsideration of the
      links.

PMID- 15557066
TI  - Randomised trial comparing prototype structures for clinical letters.

PMID- 15557067
TI  - Clinical improvement in cystic fibrosis following anti-tumourous chemotherapy.

PMID- 15557068
TI  - L-carnitine in cyclical vomiting syndrome.

PMID- 15557069
TI  - Survivin: a bifunctional inhibitor of apoptosis protein.
AB  - Survivin is a recently discovered protein belonging to the inhibitor of apoptosis
      (IAP) gene family. IAP molecules are characterized by both the presence of a zinc
      binding fold termed the baculoviral IAP repeat and the ability to suppress
      apoptosis. In addition to inhibiting apoptosis, survivin is essential for proper
      cell division. Survivin is expressed during embryonal development but is absent
      in most normal, terminally differentiated tissues. Survivin is also upregulated
      in a variety of human cancers, and its expression in tumors is associated with a
      more aggressive phenotype, shorter survival times, and a decreased response to
      chemotherapy. The exact mechanism behind the ability of survivin to inhibit
      apoptosis is still unclear. Furthermore, it is not known why this protein is
      upregulated in cancer. The purpose of this article is to provide an overview of
      the current knowledge of survivin, including its role in cell division and its
      expression in normal and neoplastic tissues. Although much of the current
      research in this field is focused on human medicine, this area also has potential
      significance for veterinary species.

PMID- 15557070
TI  - Correlation of nuclear morphometric features with animal and human World Health
      Organization International Histological Classifications of canine spontaneous
      seminomas.
AB  - The aim of this study was to correlate nuclear morphometric features with animal
      and human World Health Organization International Histological Classifications in
      canine seminomas. Twenty-three canine seminomas were classified, according to
      Animal World Health Organization International Histological Classification as
      intratubular, intratubular with signs of invasion, or diffuse and according to
      Human World Health Organization International Histological Classification
      criteria as spermatocytic and typical. The morphonuclear characteristics of
      tumors were quantitatively evaluated by means of digital cell image analyses of
      hematoxylin and eosin-stained nuclei. In particular, the mean nuclear area, mean
      nuclear perimeter, mean nuclear form factor, and their respective standard
      deviations were calculated. The relationship between the different variables and
      the tumor histologic types was assessed. On the basis of animal and human
      classification systems, statistically significant differences were observed only
      between intratubular seminomas with signs of invasion and the other two types and
      between spermatocytic and typical seminomas, respectively. In humans, it is well
      known that typical seminomas are more common and aggressive than spermatocytic
      ones. In our study, the canine seminomas classified as typical showed
      significantly larger and more variable nuclear area and perimeter than
      spermatocytic seminomas. These results support the opinion that most canine
      seminomas correspond to human spermatocytic seminomas and could explain the
      benign behavior of canine seminomas, which derive from a more differentiated type
      of germ cell.

PMID- 15557071
TI  - Skeletal changes in hemochromatosis of Salers cattle.
AB  - Hemochromatosis is an inherited defect in Salers cattle, characterized by
      increased iron absorption and wasting in young animals. Loss of teeth and soft
      bones has been reported. This study details bone changes in a prospective study
      of an affected Salers heifer and an age-matched, half-sibling control. The heifer
      fell 2 weeks before euthanasia, developed non-weight bearing lameness, and then
      became recumbent. At necropsy, the heifer was smaller than the control and had
      fractures of the humerus, femur, and ribs. Distinctive circumferential
      laminations in the outer third of the cortex were seen radiographically as layers
      of variably decreased density. In midshaft cross sections, the cortex was wider
      in some long bones, and fluorescent labeling revealed irregular and intermittent
      mineralization in the outer cortical layers. Mineral apposition rates in osteons
      of the inner cortex were decreased as compared with the control, and longitudinal
      bone formation at the growth plate was markedly decreased. Histologically, there
      were buried layers of osteopenic, poorly mineralized plexiform bone in outer
      circumferential lamellae. There was stainable iron in woven bone cores of the
      matrix. Iron was found in occasional osteoclasts as well. The mandible was
      severely affected, with loss of cortical bone as well as trabecular bone around
      the teeth and resorption of dental roots. Bone analysis revealed iron levels in
      the affected calf that were 30-50 times greater than the control and decreased
      percent ash in the outer cortex. These results indicate that periosteal dysplasia
      and osteopenia are responsible for pathologic fractures and tooth loss.

PMID- 15557072
TI  - Experimental reproduction of postweaning multisystemic wasting syndrome in pigs
      by dual infection with Mycoplasma hyopneumoniae and porcine circovirus type 2.
AB  - The objectives of this study were to investigate the interactions between
      Mycoplasma hyopneumoniae and porcine circovirus type 2 (PCV2) and to establish a
      model for studying the pathogenesis of and testing intervention strategies for
      the control of PCV2-associated porcine respiratory disease complex (PRDC). Sixty
      seven pigs were randomly assigned to four groups. Group 1 (n=17) pigs served as
      controls, group 2 (n=17) pigs were inoculated with M. hyopneumoniae, group 3
      (n=17) pigs were dual infected with M. hyopneumoniae and PCV2, and group 4 (n=16)
      pigs were inoculated with PCV2. Pigs were inoculated intratracheally with M.
      hyopneumoniae at 4 weeks of age followed by intranasal inoculation with PCV2 at 6
      weeks of age. Dual-infected pigs had moderate dyspnea, lethargy, and reduced
      weight gain. The overall severity of macroscopic lung lesions, PCV2-associated
      microscopic lesions in lung and lymphoid tissues, and the amount of PCV2-antigen
      associated with these lesions were significantly (P <0.05) higher in dual
      infected pigs compared with all other groups. Four of 17 (23.5%) dual-infected
      pigs had decreased growth rate and severe lymphoid depletion and granulomatous
      lymphadenitis associated with high amounts of PCV2-antigen consistent with
      postweaning multisystemic wasting syndrome (PMWS). PCV2-antigen in lung tissue
      was most often associated with M. hyopneumoniae-induced peribronchial lymphoid
      hyperplasia, suggesting that this is an important site for PCV2 replication in
      the lung. This study indicates that M. hyopneumoniae potentiates the severity of
      PCV2-associated lung and lymphoid lesions, increases the amount and prolongs the
      presence of PCV2-antigen, and increases the incidence of PMWS in pigs.

PMID- 15557073
TI  - Effect of bovine granulocyte colony-stimulating factor on the development of
      pneumonia caused by Mannheimia haemolytica.
AB  - The role of recruited neutrophils in Mannheimia haemolytica infection is
      controversial. We hypothesized that the neutrophilia induced by recombinant
      bovine granulocyte colony-stimulating factor (GCSF) would lead to rapid bacterial
      clearance and less severe lesions after infection with M. haemolytica. Two
      experiments (A and B) were conducted in which four calves per experiment were
      treated daily with 5 microg/kg GCSF and four calves per experiment were treated
      with saline. All 16 calves were challenged with 5 x 10(9) colony-forming units
      (cfu)/ml (experiment A) or 4.5 x 10(8) cfu/ml (experiment B) of M. haemolytica
      bacteria, into the right bronchus by bronchoscope-placed catheter. The mean
      maximal blood neutrophil counts in non-GCSF-treated and GCSF-treated calves
      before bacterial challenge were 5.6 +/- 0.7 x 10(9)/liter and 25.4 +/- 2.7 x
      10(9)/liter, respectively. Two untreated calves became neutropenic and were
      euthanatized 2 days after infection because of severe respiratory distress. GCSF
      treated calves had a 37% reduction in lung lesions compared with nontreated
      calves, and this difference was significant (P=0.04) when the effect of previous
      antibody titre to leukotoxin was considered. The effect of GCSF treatment on the
      severity of clinical signs seemed to be influenced by the antibody titre to M.
      haemolytica leukotoxin, although this effect could not be conclusively addressed.
      In conclusion, GCSF induced neutrophilia and partially protected calves against
      experimental infection with M. haemolytica. These results imply that increased
      numbers of neutrophils may, under some circumstances, protect against severe
      pneumonia caused by M. haemolytica.

PMID- 15557074
TI  - Obliterative endophlebitis in mute swans (Cygnus olor) caused by Trichobilharzia
      sp. (Digenea: Schistosomatidae) infection.
AB  - Schistosome infections in mammals cause chronic proliferative vascular lesions
      associated with the presence of adult parasites in the lumen of mesenteric and
      portal veins. In birds, however, this has never been reported. In this study, we
      found obliterative endophlebitis associated with the presence of adult
      schistosomes (Trichobilharzia sp., probably Trichobilharzia filiformis) as the
      main pathologic finding in five of eight mute swans (Cygnus olor). On histologic
      examination, the intestinal and portal veins of these swans showed moderate to
      severe, diffuse, hyperplastic endophlebitis, characterized by myointimal
      hyperplasia, often with obliteration of the vascular lumen. In addition, moderate
      to severe lymphocytic and granulocytic enteritis occurred in all eight swans
      associated with the presence of schistosome eggs in the intestinal mucosa. Other
      findings included hepatic and splenic hemosiderosis and high hepatic copper
      levels. The vascular lesions associated with Trichobilharzia sp. infection may
      have contributed to the emaciation and death of those mute swans by obstruction
      of venous return in the intestinal and portal veins.

PMID- 15557075
TI  - Expression of nitric oxide synthase 2 and cyclooxygenase-2 in swine
      experimentally infected with Actinobacillus pleuropneumoniae.
AB  - The expression of inflammatory mediators was examined in pigs experimentally
      infected with Actinobacillus pleuropneumoniae. The activity of nitric oxide
      synthase 2 (NOS2) and cyclooxygenase-2 (COX-2) was determined by measuring nitric
      oxide (NO) and prostaglandin E2 (PGE2) in bronchoalveolar lavage fluid in
      response to A. pleuropneumoniae in vivo. By in situ hybridization and
      immunohistochemistry, both NOS2 and COX-2 enzymes were detected in neutrophils
      and macrophages that had infiltrated into alveolar spaces. The sharp increase in
      PGE2 concentration preceded the increase in the concentrations of NO. NO levels
      were highly correlated with PGE2 level (rs=0.7218, P <0.05). The NO levels were
      positively correlated with lung lesion scores (rs=0.9087, P <0.05) until 24 hours
      postinoculation (hpi) as were the lung lesion scores and PGE2 levels (rs=0.925, P
      <0.01). High levels of PGE2 produced by COX-2 are generated in early infection (6
      hpi). However, in later stages of infection (12-36 hpi), there is participation
      of NO and PGE2 accompanied by coinduction of both NOS2 and COX-2.

PMID- 15557076
TI  - Early pathophysiologic feature of arthropathy in juvenile dogs induced by
      ofloxacin, a quinolone antimicrobial agent.
AB  - Arthropathy in dogs induced by ofloxacin, a quinolone antimicrobial agent, was
      pathophysiologically investigated. In the in vivo studies, ofloxacin was
      administered orally once or twice at 20 mg/kg/day to male juvenile (3-month-old,
      n=3) or adult (36-month-old, n=2) dogs, and the humeral and femoral heads were
      examined pathologically. Unlike adult dogs, fluid-filled vesicles were
      macroscopically observed on the articular surfaces of one juvenile dog 24 hours
      after a single treatment with ofloxacin. These lesions were seen in all juvenile
      dogs by twice dosing. Microscopically, fissures or cavity formations in the
      middle zone of the articular cartilage were noted only in juvenile dogs.
      Furthermore, the cartilage matrix from the abnormal area to the articular surface
      showed a decreased safranin-O staining intensity, suggesting proteoglycan
      depletion. Ultrastructurally, chondrocytes in the middle zone of juvenile dogs
      displayed dilatation of the cisternae in the rough endoplasmic reticulum as an
      initial hallmark. In the in vitro studies, chondrocytes isolated from the
      articular cartilage of naive juvenile dogs were exposed to ofloxacin at 6.3-100
      microg/ml for 24 hours. Although no changes were noted in the deoxyribonucleic
      acid synthesis, protein synthesis, or proteoglycan release at concentrations of
      up to 100 microg/ml, the proteoglycan synthesis was evidently decreased in a dose
      dependent manner from 12.5 microg/ml. The results obtained suggest that the
      inhibitory action of ofloxacin on proteoglycan syntheses in the chondrocytes may
      largely contribute to the early morphologic features in the articular cartilage
      of the juvenile dog.

PMID- 15557077
TI  - Morphologic characteristics of pulmonary macrophages in cetaceans: particular
      reference to pulmonary intravascular macrophages as a newly identified type.
AB  - We examined the morphologic characteristics of pulmonary macrophages in 42
      specimens of Odontoceti (Globicephala macrorhynchus, Grampus griseus, Tursiops
      truncatus, Stenella attenuata, Stenella coeruleoalba, Berardius bairdii), using
      light and electron microscopes as well as immunohistochemistry with SRA-E5. SRA
      E5-positive alveolar macrophages and pulmonary interstitial macrophages contained
      graphitic soots, indicating the clearance of airborne, aspirated foreign bodies.
      Pulmonary intravascular macrophages (PIMs), positive with SRA-E5, were present
      within pulmonary capillaries, attaching to applied endothelial cells by cell
      junctions. They showed cytoplasmic tubular structures of micropinocytosis
      vermiformis and erythrophagocytosis, indicating their contributory role in the
      clearance of blood-borne particles. The uptake of pathogens by PIMs may be
      associated with the inducement of acute lung injury, especially bacterial
      infectious pneumonia. This study revealed for the first time the presence of PIMs
      in cetaceans.

PMID- 15557078
TI  - Well-differentiated biphasic synovial sarcoma in the atlanto-occipital joint of a
      Holstein cow.
AB  - A 7-year-old Holstein cow developed a large cystic mass in the region between the
      atlantoaxis and larynx. The mass extended to the synovium in the atlanto
      occipital joint. Many villous projections were present on the inner surface of
      the tumor tissue, and irregular clefts were formed in the inside. Two cell types,
      epithelioid-like synovioblasts and spindle cells, were present.
      Immunohistochemical analysis showed that the cells stained positively for
      cytokeratin (AE1/AE3) and vimentin. Both cells had similar fine structures ultra
      structurally. Vacuoles present in the cytoplasm were full of an acid mucous
      substance. The tumor was diagnosed as a well-differentiated biphasic synovial
      sarcoma. This is the first report of a rare case of synovial sarcoma, from the
      viewpoint of its origin.

PMID- 15557079
TI  - Cytomegalovirus-associated discrete gastrointestinal masses in macaques infected
      with the simian immunodeficiency virus.
AB  - Cytomegalovirus (CMV)-associated gastrointestinal masses have been reported in
      human acquired immune deficiency syndrome patients. This is the first report on
      CMV-associated gastrointestinal masses in simian immunodeficiency virus (SIV)
      infected macaques. Two SIV-infected macaques presented at necropsy with multiple
      nodular or umbilicated masses within the gastrointestinal tract. In one animal,
      the masses were located throughout the gastrointestinal tract, whereas in the
      other, the masses were restricted to the proximal small intestine. Grossly, the
      masses were indistinguishable from those caused by neoplastic conditions such as
      lymphoma and, histologically, were composed of hyperplastic glandular tissue,
      dense neutrophilic infiltrates within the lamina propria, and multifocal proprial
      hemorrhage. Frequent cytomegalic cells with basophilic intranuclear inclusions
      were found in affected regions. Immunohistochemistry for CMV demonstrated
      frequent immunopositive cells within affected areas. Furthermore,
      immunohistochemistry for the proliferation marker Ki-67 demonstrated increased
      proliferation in hyperplastic glands and crypts. CMV should be considered a cause
      of discrete mass lesions in the gastrointestinal tract of SIV-infected macaques.

PMID- 15557080
TI  - Kaposiform hemangioendothelioma: the first reported case in a nonhuman animal
      species.
AB  - Kaposiform hemangioendothelioma is a rare vascular tumor that almost exclusively
      occurs in children. It is a low-grade malignant neoplasm that is locally
      aggressive but without proven metastatic potential. Herein, we describe a case of
      Kaposiform hemangioendothelioma in a 10-year-old male dog. To the best of our
      knowledge, this is the first report of this vascular tumor occurring in a
      nonhuman animal species. The tumor was located on the ventromedial surface of the
      posterior limb. Microscopic examination of the lesion revealed a multinodular
      tumor with sheets of spindled endothelial cells forming vascular slits similar to
      Kaposi's sarcoma and peripheral tumor lobules resembling capillary hemangioma.

PMID- 15557081
TI  - An oral choristoma in a foal resembling hairy polyp in humans.
AB  - A neonatal foal was presented with a 6.5-cm pedunculated mass arising from the
      upper deciduous incisors. The distal end was soft and covered by haired skin,
      whereas the proximal end was firm, covered with mucosal epithelium, and at the
      point of transection contained a fully developed tooth. Microscopically, the mass
      was covered by epidermis and mucosal epithelium and the remaining portion of the
      mass consisted of mature collagen, nonneoplastic fat and smooth muscle, and a
      single tooth within a bony socket. The mass is consistent with an oral choristoma
      and has features similar to those described for hairy polyp in humans.

PMID- 15557082
TI  - Congenital cystic polypoid rectal hamartoma in a newborn foal.
AB  - A neonatal foal with signs of rectal bleeding was diagnosed with an intraluminal
      rectal mass and intussusception on surgical exploration of the abdomen.
      Histologically, the mass consisted of cystic spaces lined by simple columnar
      epithelium with numerous goblet cells and was surrounded by thin bands of smooth
      muscle in a myxomatous stroma. Although the mass shared similarities with
      retrorectal cystic hamartoma (tailgut cyst) and juvenile polyps, described in
      human medicine, location and histologic findings were not entirely consistent
      with either condition.

PMID- 15557083
TI  - Extensive lesions of monkeypox in a prairie dog (Cynomys sp).
AB  - Monkeypox with extensive lesions was diagnosed in a prairie dog that was involved
      in a recent human outbreak of monkeypox in the Midwestern United States. Gross
      lesions included oral ulcers, pulmonary consolidation, enlarged cervical and
      thoracic lymph nodes, and multifocal, small, white umbilicated plaques in the
      gastrointestinal wall. Microscopic lesions were extensive in the lungs and
      consisted of fibrinonecrotic bronchopneumonia with vasculitis and poorly defined
      eosinophilic intracytoplasmic inclusion bodies in cells thought to be alveolar
      epithelial cells, histiocytes, and fibroblasts. Multifocal necrotizing lesions,
      often accompanied by myxedema, were also present in most of the other examined
      organs. Aggregates of pox viral particles were observed within lesions by
      transmission electron microscopy. Monkeypox virus infection was confirmed by real
      time polymerase chain reaction and virus culture at the Centers for Disease
      Control and Prevention. This report highlights the difficulties of rapid
      diagnosis of exotic or emerging diseases and further substantiates the prairie
      dog as an animal model of monkeypox.

PMID- 15557084
TI  - Capsazepine, a vanilloid antagonist, abolishes tonic responses induced by 20-HETE
      on guinea pig airway smooth muscle.
AB  - The aim of this study was to delineate the mode of action of 20-hydroxy
      eicosatetraenoic acid (20-HETE) in airway smooth muscle (ASM) cells. ASM
      metabolizes arachidonic acid by various enzymatic pathways, including the
      cytochrome P-450 (CYP-450) omega-hydroxylase, which leads to the production of 20
      HETE, a bronchoconstrictive eicosanoid. The present study demonstrated that 20
      HETE induced concentration-dependent tonic responses in ASM, whereas transient
      responses were recorded in Ca2+-free solution, suggesting an intracellular Ca2+
      release process. 20-HETE inotropic responses were abolished by 36 microM 2
      aminoethoxydiphenyl borate or 1 microM thapsigargin but were insensitive to 10
      microM ryanodine, indicating that inositol triphosphate receptors likely control
      the release of intracellular Ca2+. Sustained tension, which required Ca2+ entry,
      was partially blocked by 1 microM nifedipine (an L-type) and 100 microM Gd3+ (a
      nonselective cationic channel blocker). Moreover, in the absence of selective 20
      HETE receptor antagonists, 20-HETE tonic responses were inhibited in a
      concentration-dependent manner (0.1-10 microM) by capsazepine, a well
      characterized vanilloid receptor antagonist. Capsazepine was also observed to
      reverse cumulative responses to 20-HETE and capsaicin, a TRPV1 agonist. In
      addition, capsazepine pretreatment largely modified the sustained inotropic
      responses to 20-HETE, suggesting that 20-HETE cross-reacted with TRPV1 receptors
      with a low affinity (microM) or that its specific receptor was inhibited by the
      vanilloid antagonist. Data obtained using RHC-80267, ONO-RS-082, and
      eicosatetraynoic acid, respective inhibitors of diacylglycerol-lipase,
      phospholipase A2, and CYP-450 omega-hydroxylase, reveal that intracellular
      arachidonic acid production and its 20-HETE metabolite may be responsible for the
      activation of nonselective cationic channels and tonic responses.

PMID- 15557085
TI  - Syk tyrosine kinase participates in beta1-integrin signaling and inflammatory
      responses in airway epithelial cells.
AB  - The protein tyrosine kinase Syk is critically involved in immunoreceptor
      signaling in hematopoietic cells. Recent studies demonstrate Syk expression in
      nonhematopoietic cells, including fibroblasts, endothelial cells, hepatocytes,
      and breast epithelium. However, the role of Syk in these cells is uncertain. We
      hypothesized that Syk is expressed in respiratory epithelial cells (EC) and that
      it functions as a signaling molecule involved in inflammatory responses in the
      epithelium. With the use of immunohistochemistry, Western blot, PCR, and laser
      scanning confocal microscopy, Syk was detected in human, rat, and mouse bronchial
      epithelium in situ and in cultured human bronchial EC in primary cells and the
      cell lines HS-24 and BEAS-2B. Syk-dependent signaling pathways in EC were
      initiated by engagement of beta1-integrin receptors. Stimulation of beta1
      integrin receptors by fibronectin or antibody cross-linking caused redistribution
      of Syk from a cytoplasmic to plasma membrane localization. In stimulated cells,
      Syk and beta1-integrin colocalized. In addition, following beta1-integrin
      receptor engagement, tyrosine phosphorylation of Syk was observed. Expression of
      the intercellular adhesion molecule-1 (ICAM-1) and production of IL-6, both
      important molecules in lung inflammation, was downregulated in EC treated with
      Syk small interfering RNA or Syk inhibitor piceatannol. We propose that Syk is
      involved in signaling pathways induced by integrin engagement in airway EC. Syk
      mediated signaling regulates IL-6 and ICAM-1 expression and may be important in
      the pathophysiology of lung inflammation.

PMID- 15557086
TI  - Surfactant phospholipids and proteins are increased in fetal sheep with pulmonary
      hypertension secondary to fetal systemic arteriovenous fistula.
AB  - To determine whether prenatal surfactant storage was altered in a model of
      systemic arteriovenous fistula (SAVF) with pulmonary hypertension, a fistula was
      created between the internal jugular vein and the carotid artery in 120-day fetal
      lambs, and surfactant material was explored at 134 days. Total phospholipids
      (TPL) and disaturated phosphatidylcholine (DSPC) were increased in whole lung
      tissue. Phospholipid analysis of isolated lamellar body fraction evidenced a
      specific increase of surfactant pool size: TPL and DSPC in this fraction were
      enhanced 1.9 and 2.9 times, respectively, when referred to DNA. Although the
      steady-state level of transcripts of surfactant protein (SP)-A and SP-B was not
      found to be changed at the time of death, semiquantitative Western blot analysis
      revealed elevated SP-A and SP-B protein contents three- and twofold,
      respectively. These findings indicate markedly enhanced accumulation of
      surfactant material in the presence of surgically induced prenatal pulmonary
      hypertension. Although total lung cell number was increased by 26%, SP-B
      immunolabeling indicated that increased surfactant amount did not result from an
      increased alveolar type II cell proportion, but rather from an increased rate of
      storage. Whether similar changes in surfactant are encountered in human neonates
      with persistent pulmonary hypertension is worthy of investigation.

PMID- 15557087
TI  - Negative feedback between secretory and cytosolic phospholipase A2 and their
      opposing roles in ovalbumin-induced bronchoconstriction in rats.
AB  - Phospholipase A2 (PLA2) hydrolyzes cell membrane phospholipids (PL) to produce
      arachidonic acid and lyso-PL. The PLA2 enzymes include the secretory (sPLA2) and
      cytosolic (cPLA2) isoforms, which are assumed to act synergistically in
      production of eicosanoids that are involved in inflammatory processes. However,
      growing evidence raises the possibility that in airways and asthma-related
      inflammatory cells (eosinophils, basophils), the production of the
      bronchoconstrictor cysteinyl leukotrienes (CysLT) is linked exclusively to sPLA2,
      whereas the bronchodilator prostaglandin PGE2 is produced by cPLA2. It has been
      further reported that the capacity of airway epithelial cells to produce CysLT is
      inversely proportional to PGE2 production. This seems to suggest that sPLA2 and
      cPLA2 play opposing roles in asthma pathophysiology and the possibility of a
      negative feedback between the two isoenzymes. To test this hypothesis, we
      examined the effect of a cell-impermeable extracellular sPLA2 inhibitor on
      bronchoconstriction and PLA2 expression in rats with ovalbumin (OVA)-induced
      asthma. It was found that OVA-induced bronchoconstriction was associated with
      elevation of lung sPLA2 expression and CysLT production, concomitantly with
      suppression of cPLA2 expression and PGE2 production. These were reversed by
      treatment with the sPLA2 inhibitor, resulting in amelioration of
      bronchoconstriction and reduced CysLT production and sPLA2 expression,
      concomitantly with enhanced PGE2 production and cPLA2 expression. This study
      demonstrates, for the first time in vivo, a negative feedback between sPLA2 and
      cPLA2 and assigns opposing roles for these enzymes in asthma pathophysiology:
      sPLA2 activation induces production of the bronchoconstrictor CysLT and
      suppresses cPLA2 expression and the subsequent production of the bronchodilator
      PGE2.

PMID- 15557088
TI  - Essential role of p53 in silica-induced apoptosis.
AB  - Occupational exposure to mineral dusts, such as silica, has been associated with
      progressive pulmonary inflammation, lung cancer, and fibrosis. However, the
      mechanisms involved in this process are poorly understood. Because p53 is a key
      transcription factor regulating many important apoptosis-related genes, we
      hypothesized that p53 may play a key role in silica-induced apoptosis and that
      abnormal regulation of p53 by silica may contribute to development of lung cancer
      as well as silicosis. We used both in vitro and in vivo studies to test this
      hypothesis. Treatment of JB6 cells carrying a p53-luciferase reporter plasmid
      with silica caused dose-dependent p53 transactivation. Western blot indicates
      that silica not only stimulated p53 protein expression but also caused p53
      phosphorylation at Ser392. TUNEL and DNA fragmentation analysis show that silica
      caused apoptosis in both JB6 cells and wild-type p53 (p53+/+) fibroblasts but not
      in p53-deficient (p53-/-) fibroblasts. Similar results were obtained by in vivo
      studies. Intratracheal instillation of mice with silica induced apoptosis in the
      lung of p53+/+ mice, whereas this induction was significantly inhibited in p53-/-
      mice. Confocal image analysis indicates that most apoptotic cells induced by
      silica were alveolar macrophages. These results demonstrate for the first time
      that silica induces p53 transactivation via induction of p53 protein expression
      and phosphorylation of p53 protein and that p53 plays a crucial role in the
      signal transduction pathways of silica-induced apoptosis. This finding may
      provide an important link in understanding the molecular mechanisms of silica
      induced carcinogenesis and pathogenesis in the lung.

PMID- 15557089
TI  - Differential effects of alpha- and beta-defensin on cytokine production by
      cultured human bronchial epithelial cells.
AB  - Defensins are cysteine-rich cationic antimicrobial peptides that play an
      important role in innate immunity and are known to contribute to the regulation
      of host adaptive immunity. In addition to direct antimicrobial activities, it has
      been recently reported that alpha-defensins, mainly present in neutrophils in the
      lung, have a cytotoxic effect and induce IL-8 production from airway epithelial
      cells. Although beta-defensins are expressed in epithelial cells in various
      tissues, including lung, there are no reports of their effects on cytokine
      synthesis in airway epithelial cells. The aim of the present study was to
      determine the effects of both alpha- and beta-defensins on the cytokine
      production, transcription factor binding activity, and cytotoxicity in primary
      cultured human bronchial epithelial cells (HBECs). We used human neutrophil
      peptide-1 (HNP-1; alpha-defensin) and human beta-defensin-2 (HBD-2) to stimulate
      HBECs. The results showed that treatment of HBECs with HNP-1, but not HBD-2,
      increased IL-8 and IL-1beta mRNA expression in a dose-dependent manner and also
      enhanced IL-8 protein secretion and NF-kappaB DNA binding activity. The 24-h
      treatments with >20 microg/ml of HNP-1 or >50 microg/ml of HBD-2 were cytotoxic
      to HBECs. These results suggest that alpha- and beta-defensins have different
      effects on cytokine synthesis by airway epithelial cells, and we speculate that
      they play different roles in inflammatory lung diseases.

PMID- 15557090
TI  - Functional analysis of methylthioribose kinase genes in plants.
AB  - Through a biochemical and a genetic approach, we have identified several plant
      genes encoding methylthioribose (MTR) kinase, an enzyme involved in recycling of
      methionine through the methylthioadenosine (MTA) cycle. OsMTK1, an MTR kinase
      from rice (Oryza sativa), is 48.6 kD in size and shows cooperative kinetics with
      a V(max) of 4.9 pmol/min and a K0.5 of 16.8 microm. MTR kinase genes are the
      first genes to be identified from the MTA cycle in plants. Insertional
      mutagenesis of the unique AtMTK gene in Arabidopsis (Arabidopsis thaliana)
      resulted in an inability of plants to grow on MTA as a supplemental sulfur
      source. MTK knock-out plants were not impaired in growth under standard
      conditions, indicating that the MTA cycle is a nonessential metabolic pathway in
      Arabidopsis when sulfur levels are replete. In rice, OsMTK genes were strongly up
      regulated in shoots and roots when plants were exposed to sulfur starvation. Gene
      expression was largely unaffected by lack of nitrogen or iron in the nutrient
      solution, indicating that OsMTK regulation was linked specifically to sulfur
      metabolism.

PMID- 15557091
TI  - Polyphyletic origin of pyrrolizidine alkaloids within the Asteraceae. Evidence
      from differential tissue expression of homospermidine synthase.
AB  - The evolution of pathways within plant secondary metabolism has been studied by
      using the pyrrolizidine alkaloids (PAs) as a model system. PAs are constitutively
      produced by plants as a defense against herbivores. The occurrence of PAs is
      restricted to certain unrelated families within the angiosperms. Homospermidine
      synthase (HSS), the first specific enzyme in the biosynthesis of the necine base
      moiety of PAs, was originally recruited from deoxyhypusine synthase, an enzyme
      involved in the posttranslational activation of the eukaryotic initiation factor
      5A. Recently, this gene recruitment has been shown to have occurred several times
      independently within the angiosperms and even twice within the Asteraceae. Here,
      we demonstrate that, within these two PA-producing tribes of the Asteraceae,
      namely Senecioneae and Eupatorieae, HSS is expressed differently despite
      catalyzing the same step in PA biosynthesis. Within Eupatorium cannabinum, HSS is
      expressed uniformly in all cells of the root cortex parenchyma, but not within
      the endodermis and exodermis. Within Senecio vernalis, HSS expression has been
      previously identified in groups of specialized cells of the endodermis and the
      adjacent root cortex parenchyma. This expression pattern was confirmed for
      Senecio jacobaea as well. Furthermore, the expression of HSS in E. cannabinum is
      dependent on the development of the plant, suggesting a close linkage to plant
      growth.

PMID- 15557092
TI  - A plant-specific kinesin binds to actin microfilaments and interacts with
      cortical microtubules in cotton fibers.
AB  - A novel kinesin, GhKCH1, has been identified from cotton (Gossypium hirsutum)
      fibers. GhKCH1 has a centrally located kinesin catalytic core, a signature neck
      peptide of minus end-directed kinesins, and a unique calponin homology (CH)
      domain at its N terminus. GhKCH1 and other CH domain-containing kinesins (KCHs)
      belong to a distinct branch of the minus end-directed kinesin subfamily. To date
      the KCH kinesins have been found only in higher plants. Because the CH domain is
      often found in actin-binding proteins, we proposed that GhKCH1 might play a role
      in mediating dynamic interaction between microtubules and actin microfilaments in
      cotton fibers. In an in vitro actin-binding assay, GhKCH1's N-terminal region
      including the CH domain interacted directly with actin microfilaments. In cotton
      fibers, GhKCH1 decorated cortical microtubules in a punctate manner. Occasionally
      GhKCH1 was found to be associated with transverse-cortical actin microfilaments,
      but never with axial actin cables in cotton fibers. Localization of GhKCH1 on
      cortical microtubules was independent of the integrity of actin microfilaments.
      Thus, GhKCH1 may play a role in organizing the actin network in coordination with
      the cortical microtubule array. These data also suggest that flowering plants may
      employ unique KCHs to coordinate actin microfilaments and microtubules during
      cell growth.

PMID- 15557093
TI  - Exploring the temperature-stress metabolome of Arabidopsis.
AB  - Metabolic profiling analyses were performed to determine metabolite temporal
      dynamics associated with the induction of acquired thermotolerance in response to
      heat shock and acquired freezing tolerance in response to cold shock. Low-M(r)
      polar metabolite analyses were performed using gas chromatography-mass
      spectrometry. Eighty-one identified metabolites and 416 unidentified mass
      spectral tags, characterized by retention time indices and specific mass
      fragments, were monitored. Cold shock influenced metabolism far more profoundly
      than heat shock. The steady-state pool sizes of 143 and 311 metabolites or mass
      spectral tags were altered in response to heat and cold shock, respectively.
      Comparison of heat- and cold-shock response patterns revealed that the majority
      of heat-shock responses were shared with cold-shock responses, a previously
      unknown relationship. Coordinate increases in the pool sizes of amino acids
      derived from pyruvate and oxaloacetate, polyamine precursors, and compatible
      solutes were observed during both heat and cold shock. In addition, many of the
      metabolites that showed increases in response to both heat and cold shock in this
      study were previously unlinked with temperature stress. This investigation
      provides new insight into the mechanisms of plant adaptation to thermal stress at
      the metabolite level, reveals relationships between heat- and cold-shock
      responses, and highlights the roles of known signaling molecules and protectants.

PMID- 15557094
TI  - Analysis in vitro of the enzyme CRTISO establishes a poly-cis-carotenoid
      biosynthesis pathway in plants.
AB  - Most enzymes in the central pathway of carotenoid biosynthesis in plants have
      been identified and studied at the molecular level. However, the specificity and
      role of cis-trans-isomerization of carotenoids, which occurs in vivo during
      carotene biosynthesis, remained unresolved. We have previously cloned from tomato
      (Solanum lycopersicum) the CrtISO gene, which encodes a carotene cis-trans
      isomerase. To study the biochemical properties of the enzyme, we developed an
      enzymatic in vitro assay in which a purified tomato CRTISO polypeptide
      overexpressed in Escherichia coli cells is active in the presence of an E. coli
      lysate that includes membranes. We show that CRTISO is an authentic carotene
      isomerase. Its catalytic activity of cis-to-trans isomerization requires redox
      active components, suggesting that isomerization is achieved by a reversible
      redox reaction acting at specific double bonds. Our data demonstrate that CRTISO
      isomerizes adjacent cis-double bonds at C7 and C9 pairwise into the trans
      configuration, but is incapable of isomerizing single cis-double bonds at C9 and
      C9'. We conclude that CRTISO functions in the carotenoid biosynthesis pathway in
      parallel with zeta-carotene desaturation, by converting 7,9,9'-tri-cis
      neurosporene to 9'-cis-neurosporene and 7'9'-di-cis-lycopene into all-trans
      lycopene. These results establish that in plants carotene desaturation to
      lycopene proceeds via cis-carotene intermediates.

PMID- 15557095
TI  - Plant-specific microtubule-associated protein SPIRAL2 is required for anisotropic
      growth in Arabidopsis.
AB  - In diffusely growing plant cells, cortical microtubules play an important role in
      regulating the direction of cell expansion. Arabidopsis (Arabidopsis thaliana)
      spiral2 (spr2) mutant is defective in directional cell elongation and exhibits
      right-handed helical growth in longitudinally expanding organs such as root,
      hypocotyl, stem, petiole, and petal. The growth of spr2 roots is more sensitive
      to microtubule-interacting drugs than is wild-type root growth. The SPR2 gene
      encodes a plant-specific 94-kD protein containing HEAT-repeat motifs that are
      implicated in protein-protein interaction. When expressed constitutively, SPR2
      green fluorescent protein fusion protein complemented the spr2 mutant phenotype
      and was localized to cortical microtubules as well as other mitotic microtubule
      arrays in transgenic plants. Recombinant SPR2 protein directly bound to taxol
      stabilized microtubules in vitro. Furthermore, SPR2-specific antibody and mass
      spectrometry identified a tobacco (Nicotiana tabacum) SPR2 homolog in highly
      purified microtubule-associated protein fractions from tobacco BY-2 cell
      cultures. These results suggest that SPR2 is a novel microtubule-associated
      protein and is required for proper microtubule function involved in anisotropic
      growth.

PMID- 15557097
TI  - Genotypic and developmental evidence for the role of plasmodesmatal regulation in
      cotton fiber elongation mediated by callose turnover.
AB  - Cotton fibers are single-celled hairs that elongate to several centimeters long
      from the seed coat epidermis of the tetraploid species (Gossypium hirsutum and
      Gossypium barbadense). Thus, cotton fiber is a unique system to study the
      mechanisms of rapid cell expansion. Previous work has shown a transient closure
      of plasmodesmata during fiber elongation (Y.-L. Ruan, D.J. Llewellyn, R.T.
      Furbank [2001] Plant Cell 13: 47-60). To examine the importance of this closure
      in fiber elongation, we compared the duration of the plasmodesmata closure among
      different cotton genotypes differing in fiber length. Confocal imaging of the
      membrane-impermeant fluorescent molecule carboxyfluorescein revealed a genotypic
      difference in the duration of the plasmodesmata closure that positively
      correlates with fiber length among three tetraploid genotypes and two diploid
      progenitors. In all cases, the closure occurred at the rapid phase of elongation.
      Aniline blue staining and immunolocalization studies showed that callose
      deposition and degradation at the fiber base correlates with the timing of
      plasmodesmata closure and reopening, respectively. Northern analyses showed that
      the expression of a fiber-specific beta-1,3-glucanase gene, GhGluc1, was
      undetectable when callose was deposited at the fiber base but became evident at
      the time of callose degradation. Genotypically, the level of GhGluc1 expression
      was high in the short fiber genotype and weak in the intermediate and long fiber
      genotypes. The data provide genotypic and developmental evidence that (1)
      plasmodesmata closure appears to play an important role in elongating cotton
      fibers, (2) callose deposition and degradation may be involved in the
      plasmodesmata closure and reopening, respectively, and (3) the expression of
      GhGluc1 could play a role in this process by degrading callose, thus opening the
      plasmodesmata.

PMID- 15557096
TI  - In vivo dynamics and differential microtubule-binding activities of MAP65
      proteins.
AB  - Plant cells produce different microtubule arrays that are essential for cell
      division and morphogenesis without equivalent in other eukaryotes. Microtubule
      associated proteins influence the behavior of microtubules that is presumed to
      culminate into transitions from one array to another. We analyzed the microtubule
      binding properties of three Arabidopsis (Arabidopsis thaliana) members, AtMAP65
      1, AtMAP65-4, and AtMAP65-5, in live cells using laser scanning confocal
      microscopy. Depending on the overall organization of the cortical array, AtMAP65
      1-GFP (green fluorescent protein) and AtMAP65-5-GFP associated with a subset of
      microtubules. In cells containing both coaligned and oblique microtubules,
      AtMAP65-1-GFP and AtMAP65-5-GFP tended to be associated with the coaligned
      microtubules. Cortical microtubules labeled with AtMAP65-1-GFP and AtMAP65-5-GFP
      appeared as thick bundles and showed more resistance to microtubule-destabilizing
      drugs. The polymerization rates of AtMAP65-1-GFP and AtMAP65-5-GFP microtubules
      were similar to those of tubulin-GFP marked microtubules but were different from
      AtEB1a-GFP, a microtubule plus-end-binding EB1-like protein that stimulated
      polymerization. By contrast, depolymerization rates of AtMAP65-1-GFP- and AtMAP65
      5-GFP-labeled microtubules were reduced. AtMAP65-1-GFP associated with
      polymerizing microtubules within a bundle, and with fixed microtubule termini,
      suggesting that AtMAP65-1's function is to bundle and stabilize adjacent
      microtubules of the cortex. Polymerization within a bundle took place in either
      direction so that bundling occurred between parallel or antiparallel aligned
      microtubules. AtMAP65-4-GFP did not label cortical microtubules or the
      preprophase band, despite continuous expression driven by the 35S promoter, and
      its subcellular localization was restricted to microtubules that rearranged to
      form a spindle and the polar sides of the spindle proper. The expression of
      AtMAP65-4 peaked at mitosis, in agreement with a function related to spindle
      formation, whereas AtMAP65-1 and AtMAP65-5 were expressed throughout the cell
      cycle.

PMID- 15557098
TI  - Progression through meiosis I and meiosis II in Arabidopsis anthers is regulated
      by an A-type cyclin predominately expressed in prophase I.
AB  - Meiosis is often described as a special case of cell division since it differs
      from mitosis in having two nuclear divisions without an intervening S-phase. It
      will be of great interest to uncover what molecular mechanisms underlie these
      special features of meiosis. We previously reported that the tardy asynchronous
      meiosis (tam) mutant of Arabidopsis (Arabidopsis thaliana) is slower in cell
      cycle progression in male meiosis. Here we report that TAM encodes the A-type
      cyclin, CYCA1;2. The point mutation in tam replaced a conserved threonine with an
      isoleucine in the linker region between the alpha4 and alpha5 helices of the
      first cyclin fold. By studying the dynamics of a CYCA1;2-green fluorescent
      protein fusion protein under the control of the CYCA1;2 promoter, we found that
      the fusion protein was most abundant at pachytene, but was undetectable from late
      prophase I until telophase II. Nonetheless, cell cycle progression in tam was
      delayed in both pachytene and meiosis II. We conclude either that the CYCA1;2
      produced in prophase I indirectly regulates meiosis II progression, or that a
      very low level of CYCA1;2 directly regulates meiosis II progression. Either of
      these scenarios is a deviation from the typical mode of action of mitotic cyclins
      in mitosis and meiosis I, in which each nuclear division is coupled with a peak
      of expression of mitotic cyclins.

PMID- 15557099
TI  - A green fluorescent protein fusion to actin-binding domain 2 of Arabidopsis
      fimbrin highlights new features of a dynamic actin cytoskeleton in live plant
      cells.
AB  - The actin cytoskeleton coordinates numerous cellular processes required for plant
      development. The functions of this network are intricately linked to its dynamic
      arrangement, and thus progress in understanding how actin orchestrates cellular
      processes relies on critical evaluation of actin organization and turnover. To
      investigate the dynamic nature of the actin cytoskeleton, we used a fusion
      protein between green fluorescent protein (GFP) and the second actin-binding
      domain (fABD2) of Arabidopsis (Arabidopsis thaliana) fimbrin, AtFIM1. The GFP
      fABD2 fusion protein labeled highly dynamic and dense actin networks in diverse
      species and cell types, revealing structural detail not seen with alternative
      labeling methods, such as the commonly used mouse talin GFP fusion (GFP-mTalin).
      Further, we show that expression of the GFP-fABD2 fusion protein in Arabidopsis,
      unlike GFP-mTalin, has no detectable adverse effects on plant morphology or
      development. Time-lapse confocal microscopy and fluorescence recovery after
      photobleaching analyses of the actin cytoskeleton labeled with GFP-fABD2 revealed
      that lateral-filament migration and sliding of individual actin filaments or
      bundles are processes that contribute to the dynamic and continually reorganizing
      nature of the actin scaffold. These new observations of the dynamic actin
      cytoskeleton in plant cells using GFP-fABD2 reveal the value of this probe for
      future investigations of how actin filaments coordinate cellular processes
      required for plant development.

PMID- 15557100
TI  - Extracellular calmodulin-induced stomatal closure is mediated by heterotrimeric G
      protein and H2O2.
AB  - Extracellular calmodulin (ExtCaM) exerts multiple functions in animals and
      plants, but the mode of ExtCaM action is not well understood. In this paper, we
      provide evidence that ExtCaM stimulates a cascade of intracellular signaling
      events to regulate stomatal movement. Analysis of the changes of cytosolic free
      Ca2+ ([Ca2+]cyt) and H2O2 in Vicia faba guard cells combined with epidermal strip
      bioassay suggests that ExtCaM induces an increase in both H2O2 levels and
      [Ca2+]cyt, leading to a reduction in stomatal aperture. Pharmacological studies
      implicate heterotrimeric G protein in transmitting the ExtCaM signal, acting
      upstream of [Ca2+]cyt elevation, and generating H2O2 in guard cell responses. To
      further test the role of heterotrimeric G protein in ExtCaM signaling in stomatal
      closure, we checked guard cell responses in the Arabidopsis (Arabidopsis
      thaliana) Galpha-subunit-null gpa1 mutants and cGalpha overexpression lines. We
      found that gpa1 mutants were insensitive to ExtCaM stimulation of stomatal
      closure, whereas cGalpha overexpression enhanced the guard cell response to
      ExtCaM. Furthermore, gpa1 mutants are impaired in ExtCaM induction of H2O2
      generation in guard cells. Taken together, our results strongly suggest that
      ExtCaM activates an intracellular signaling pathway involving activation of a
      heterotrimeric G protein, H2O2 generation, and changes in [Ca2+]cyt in the
      regulation of stomatal movements.

PMID- 15557101
TI  - Identification and characterization of a Ca2+-dependent actin filament-severing
      protein from lily pollen.
AB  - It is well known that a tip-focused intracellular Ca2+ gradient and the meshwork
      of short actin filaments at the tip region are necessary for pollen tube growth.
      However, little is known about the connections between the two factors. Here, a
      novel Ca2+-dependent actin-binding protein with molecular mass of 41 kD from lily
      (Lilium davidii) pollen (LdABP41) was isolated and purified with DNase I
      chromatography. Our purification procedure yielded about 0.6 mg of LdABP41 with
      >98% purity from 10 g of lily pollen. At least two isoforms with isoelectric
      points of 5.8 and 6.0 were detected on two-dimensional gels. The results of N
      terminal sequencing and mass-spectrometry analysis of LdABP41 showed that both
      isoforms shared substantial similarity with trumpet lily (Lilium longiflorum)
      villin and other members of the gelsolin superfamily. Negative-stained electron
      microscope images showed that LdABP41 severed in vitro-polymerized lily pollen F
      actin into short actin filaments in a Ca2+-sensitive manner. Microinjection of
      the anti-LdABP41 antibody into germinated lily pollen demonstrated that the
      protein was required for pollen tube growth. The results of immunolocalization of
      the protein showed that it existed in the cytoplasm of the pollen tube,
      especially focused in the tip region. Our results suggest that LdABP41 belongs to
      the gelsolin superfamily and may play an important role in controlling actin
      organization in the pollen tube tip by responding to the oscillatory, tip-focused
      Ca2+ gradient.

PMID- 15557102
TI  - Reorganization and in vivo dynamics of microtubules during Arabidopsis root hair
      development.
AB  - Root hairs emerge from epidermal root cells (trichoblasts) and differentiate by
      highly localized tip growth. Microtubules (MTs) are essential for establishing
      and maintaining the growth polarity of root hairs. The current knowledge about
      the configuration of the MT cytoskeleton during root hair development is largely
      based on experiments on fixed material, and reorganization and in vivo dynamics
      of MTs during root hair development is at present unclear. This in vivo study
      provides new insights into the mechanisms of MT (re)organization during root hair
      development in Arabidopsis (Arabidopsis thaliana). Expression of a binding site
      of the MT-associated protein-4 tagged with green fluorescent protein enabled
      imaging of MT nucleation, growth, and shortening and revealed distinct MT
      configurations. Depending on the dynamics of the different MT populations during
      root hair development, either repeated two-dimensional (x, y, t) or repeated
      three-dimensional (x, y, z, t) scanning was performed. Furthermore, a new image
      evaluation tool was developed to reveal important data on MT instability. The
      data show how MTs reorient after apparent contact with other MTs and support a
      model for MT alignment based on repeated reorientation of dynamic MT growth.

PMID- 15557103
TI  - Injectable dexamethasone administration enhances cortical GABAergic neuronal
      differentiation in a novel model of postnatal steroid therapy in mice.
AB  - Injectable dexamethasone (DXM) is widely used during the postnatal period in
      premature infants. However, this treatment has been associated with an increased
      incidence of neuromotor disorders. Few studies have directly addressed the impact
      of DXM therapy on neuronal differentiation. We used a murine model of postnatal
      steroid therapy in which mouse pups aged 3 and 4 postnatal days (P) received
      intraperitoneal injections of 1 mg . kg(-1) . 12 h(-1) of an injectable
      preparation that contained DXM and sulfites (DXM), pure DXM, or sulfites. The
      animals were weighed before they were killed on P5, P10, or P21, and their brains
      were investigated by immunohistochemistry with markers for neuronal
      differentiation. DXM administration was associated with a 20-30% reduction in
      body and brain weight gains and in cortical thickness on P5 and P10. gamma-Amino
      butyric acid+ (GABA+) interneuron density was significantly increased (+50%) in
      the cerebral cortex of the animals given injectable DXM on P5 to P21 compared
      with controls (p < 0.01). In parallel, the density of cortical neurons expressing
      two interneuron markers (calbindin 28-kD and calretinin) increased significantly.
      These alterations occurred with injectable DXM but not with pure DXM or sulfites
      alone. In contrast, none of the study treatments modified the expression of other
      markers for neuronal transmission or axon myelination. In the animals that were
      given injectable DXM, cleaved caspase 3 antibody showed increased neuronal cell
      death, but calbindin antibody did not. In conclusion, in a murine model of
      postnatal steroid therapy, injectable DXM induced a selective increase in
      GABAergic neurons in the cerebral cortex.

PMID- 15557104
TI  - Vessel-specific regulation of angiotensin II receptor subtypes during ovine
      development.
AB  - Umbilical and systemic responses to angiotensin II differ in term fetal sheep,
      and peripheral vascular responses are attenuated or absent before and after
      birth. These observations may reflect developmental differences in angiotensin II
      receptor (AT) subtypes in vascular smooth muscle (VSM). Studies of AT subtype
      ontogeny and regulation are generally limited to the aorta, which may not be
      extrapolated to other arteries, and neither is completely described during ovine
      development. We therefore characterized VSM AT subtype expression and regulation
      throughout an extended period of development in umbilical and carotid artery and
      aorta from fetal (85-146 d gestation), postnatal (5-23 d), and adult sheep,
      measuring AT(1) and AT(2) mRNA and protein and performing immunohistochemistry.
      Parallel increases in umbilical AT(1) mRNA and protein began early in gestation
      and continued to term, and although AT(2) mRNA was unchanged, protein levels
      decreased >90% at term. Fetal carotid AT(1) mRNA was <40% of adult values and
      unchanged before birth; however, AT(1) protein rose >2-fold at term. After birth,
      AT(1) mRNA increased to 85% of adult values and was associated with another 2
      fold rise in protein. In contrast, carotid AT(2) mRNA and protein fell in
      parallel throughout development and were barely detectable in the newborn and the
      adult. Immunostaining was consistent with observations in both arteries. A third
      pattern occurred in aortic VSM. The ontogeny of AT subtype expression and
      regulation is vessel specific, with changes in umbilical VSM beginning very early
      in development. Although the mechanisms that regulate mRNA and protein expression
      are unclear, these changes parallel differences in VSM maturation and function
      and local blood flow.

PMID- 15557105
TI  - Calcium transients in infant human atrial myocytes.
AB  - Isolated infant human atrial cells have a slower early repolarization than adult
      human atrial cells. In addition, from room temperature voltage-clamp studies,
      infant cells have lower basal L-type calcium currents than adult cells. We
      hypothesized that the slower repolarization increases the calcium transient of
      infant human atrial cells. Atrial myocytes were enzymatically dissociated from
      biopsies of human right atrial appendages of infant (3-8 mo) patients who were
      undergoing open-heart surgery. Intracellular calcium transients were measured
      with fluorescence microscopy with application of either square waves or action
      potential waveforms at physiologic temperature. After repetitive application (1
      Hz) of 100-ms duration conditioning depolarizations to 10 mV (from -80 mV), a
      test pulse of varying duration (DeltaT; 2-100 ms) produced smaller transients
      (expressed as percentage of the last conditioning pulse) at shorter durations (33
      +/- 7% for DeltaT = 2 ms, 80 +/- 4% for DeltaT = 25 ms). With repetitive
      application of either adult or infant prerecorded action potentials to infant
      cells, the cells had a decreased calcium transient with the adult action
      potential (F/F(0) 2.2 +/- 0.4 for infant action potential versus 1.6 +/- 0.2 for
      adult action potential; n = 7; p < 0.05). The delayed early repolarization of
      infant cells alters the Ca(2+) transient, which may compensate for the lower
      availability of basal calcium current in infant cells. The steep relationship
      that we have demonstrated between test-pulse duration and the calcium transient
      suggests that modulation of the early repolarization phase of the action
      potential may be of great significance in modulating excitation-contraction
      coupling.

PMID- 15557106
TI  - Androgen and estrogen treatment, alone or in combination, differentially
      influences bone maturation and hypothalamic mechanisms that time puberty in the
      male rhesus monkey (Macaca mulatta).
AB  - In higher primates, the mechanisms that govern the ontogeny of gonadotropin
      releasing hormone pulse generator activity and that, therefore, dictate the
      timing of the onset of puberty remain intriguingly elusive. Groups of three
      infant agonadal male monkeys were treated with sex steroids [17beta-estradiol
      (E(2)), testosterone (T), or dihydrotestosterone (DHT)] for the first year of
      life to advance bone age (BA). E(2) and T resulted in a significant advancement
      of BA, and a pubertal BA of 130 wk was attained at a mean chronological age of 64
      and 67 wk, respectively. In contrast, DHT failed to advance BA during treatment
      but stimulated linear growth. All animals exhibited a pubertal resurgence in LH
      secretion, but the timing of this developmental event did not differ between
      treatment and control groups (the mean for all animals was 117.7 +/- 8.9 wk). Two
      of the three T-treated animals, however, displayed a pubertal LH resurgence at a
      remarkably young age (70 and 76 wk of age) that coincided with T withdrawal.
      During the period of steroid treatment, all three groups were significantly
      heavier than the controls. The rate of body weight gain was most rapid in the DHT
      treated group. Steroid treatments also resulted in accelerated linear growth.
      Body weight gain and linear growth continued at the same rate as controls after
      withdrawal of treatment. These data indicate that attainment of a pubertal BA may
      be a necessary but not a sufficient factor to trigger the onset of puberty. The
      results not only are consistent with the view that androgen-induced skeletal
      maturation in males is mediated by estrogen receptor activity but also indicate
      that androgen receptor activity contributes to the pubertal growth spurt in
      males.

PMID- 15557107
TI  - Nuclear accumulation of beta-catenin occurs commonly in the epithelial cells of
      juvenile polyps.
AB  - In the two conditions juvenile polyps (JPs) and juvenile polyposis coli (JPC),
      colonic polyps may have overlapping histologic and phenotypic appearance, but JPC
      confers a significant risk for colon adenocarcinoma. Although not thought to
      contain adenomatous polyposis coli (APC) mutations, the status of beta-catenin
      and full-length APC protein expression in JPs is not known. We evaluated beta
      catenin and full-length APC protein expression in JPs from children with JPs and
      JPC. Cases were identified through endoscopic procedure records.
      Immunohistochemistry was performed for beta-catenin and full-length APC protein.
      Loss of heterozygosity at the APC gene locus on chromosome 5 was assessed using
      two APC-linked microsatellite markers. Polyp and normal colonic tissue were
      analyzed from 36 children with JPs and 9 with JPC. Both APC and beta-catenin
      immunoreactivity were present in epithelial cells from all samples but in
      different patterns. In all normal colon and polyp samples, APC expression was
      cytoplasmic with maximal immunoreactivity in the goblet cells. In contrast, beta
      catenin immunoreactivity in epithelial cells was limited to the plasma membrane
      in normal colon but was both cytoplasmic and nuclear in all 45 JPs. No evidence
      of APC gene loss of heterozygosity was found. In polyps from children with JPs
      and JPC, nuclear beta-catenin accumulation is a consistent feature, and it is not
      due to APC gene mutation or loss of full-length APC protein expression. Thus,
      beta-catenin accumulation may be intrinsic to the formation of juvenile-type
      polyps through an as-yet-undefined mechanism.

PMID- 15557108
TI  - G-CSF induces stabilization of ETS protein Fli-1 during myeloid cell development.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a growth factor that regulates
      the production and function of neutrophils. G-CSF has been used to treat
      neutropenia in neonates, pediatric cancer patients, and patients undergoing stem
      cell transplantation. The regulation of transcription factors mediating G-CSF
      activity has not been well characterized. The goal of this study was to examine
      the regulation of the ETS binding protein, Friend leukemia integration site 1
      (Fli-1), in myeloid cells treated with G-CSF. Fli-1 has oncogenic properties in
      humans and mice, and plays a role in vascular and hematopoietic cell development.
      We previously reported that Fli-1 and the serum response factor bind at adjacent
      sites within the serum response element-1 of the early growth response gene-1
      promoter in the murine myeloid leukemic cell line, NFS60. We also identified that
      Fli-1 DNA binding increased in G-CSF-treated cells compared with untreated cells.
      To determine whether the change in binding activity is due to increased Fli-1
      transcription or protein stability, we examined endogenous Fli-1 expression in G
      CSF-treated or -untreated NFS60 cells. Our results demonstrated that levels of
      Fli-1 protein, but not RNA, were higher in extracts from cells treated with G
      CSF. The increase in Fli-1 protein was also dependent on protein synthesis.
      Finally, we showed that the half-life of Fli-1 is prolonged in G-CSF-treated
      cells compared with control-treated cells. These results suggest that G-CSF
      induces stabilization of Fli-1 protein in myeloid cells, thus proposing a novel
      mechanism by which hematopoietic growth factors regulate transcription factors.

PMID- 15557109
TI  - Effects of rapamycin in the Eker rat model of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) presents in the pediatric population with a
      constellation of benign tumors that affect the brain, heart, kidney, lung, and
      skin. No therapy has been shown to halt disease progression or to prevent its
      onset. The pathogenesis of TSC stems from the inactivation of one of the two TSC
      genes, TSC1 and TSC2. A key function of these genes is to regulate the mammalian
      target of rapamycin (mTOR) pathway in response to cellular energy and nutrient
      and growth factor availability. Consequently, TSC-related tumors exhibit
      uncontrolled activation of mTOR and its effectors. Previous work has shown that a
      specific mTOR inhibitor, rapamycin, effectively down-regulated mTOR activity in
      renal tumors of Eker rats that carry a germline Tsc2 mutation. Using this model,
      we investigated the effects of rapamycin on pituitary and renal tumors. We
      observed that rats with pituitary tumors had significantly shorter survival than
      those without pituitary pathology. Treatment with rapamycin effectively improved
      their clinical state and prolonged their survival. Rapamycin also resulted in a
      significant decrease in the size of the Tsc2-related renal tumors. In both types
      of pathology, tumor response was accompanied by down-regulation of ribosomal S6
      kinase activity, reduction in cell size, and induction of apoptosis. Evidence for
      drug resistance was found in a small percentage of lesions after prolonged
      therapy. When rapamycin was given before onset of disease, subsequent development
      of macroscopic renal tumors was reduced, but no effect on the number of
      microscopic precursor lesions was found. We conclude that rapamycin-sensitive
      mTOR activity was critical to tumor progression in the Eker rat model, but
      rapamycin is unlikely to eradicate all disease as a result of the development of
      drug resistance. Our data also suggest the role of a rapamycin-insensitive
      pathway during tumor initiation.

PMID- 15557110
TI  - Tales from the crypt: beta-catenin in the development of juvenile polyps:
      commentary on the article by Iwamoto et al. on page 4.

PMID- 15557111
TI  - Mechanisms underlying reduced apoptosis in neonatal neutrophils.
AB  - Apoptosis, which leads to phagocytosis by mononuclear cells, represents the
      primary mechanism for removing neutrophils from inflamed tissues and minimizing
      injury. The present studies show that membrane phosphatidylserine turnover and
      permeability, as well as DNA fragmentation, were reduced in neutrophils from
      neonates when compared with adults. The activity of caspase 3 and expression of
      the proapoptotic proteins Bax, Bad, and Bak were also decreased in neonatal
      relative to adult neutrophils. These findings are consistent with impaired
      apoptosis in neonatal cells, which may contribute to prolonged inflammation in
      infants after oxidative stress or infection. Neutrophil apoptosis is induced by
      endogenous ligands such as Fas (FasL), which engage death receptors of the tumor
      necrosis factor/nerve growth factor superfamily, including Fas receptor (FasR).
      We found that expression of FasR was decreased in neonatal when compared with
      adult cells. Moreover, neonatal neutrophils did not undergo apoptosis in response
      to anti-FasR antibody and exhibited impaired chemotaxis to soluble FasL. However,
      in both adult and neonatal cells, p38 mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase inhibitors blocked Fas-induced activity. These data
      suggest that prolonged survival of neonatal neutrophils at injured sites is due,
      in part, to reduced responsiveness to FasL. This may be related to decreased
      expression of both FasR and Bcl-2-family proteins that mediate neutrophil
      apoptosis.

PMID- 15557112
TI  - Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein
      trafficking resulting from a spontaneous mutation in the surfactant protein C
      gene.
AB  - Human surfactant protein C (hSP-C(1-197)) is synthesized as a 197 amino acid
      proprotein and cleaved to a mature 3.7 kD form. Although interstitial lung
      disease in patients with mutations of the hSP-C gene is becoming increasingly
      recognized, the mechanisms linking molecular events with clinical pathogenesis
      are not fully defined. We describe a full-term infant with respiratory
      insufficiency associated with a spontaneous heterozygous mutation resulting in a
      substitution of lysine for glutamic acid at position 66 (= E66K) of the proximal
      hSP-C COOH flanking propeptide. Lung histology and biochemical studies of the
      index patient (hSP-C(E66K)) revealed nonspecific interstitial pneumonia,
      increased alveolar total phospholipid lacking phosphatidylglycerol, and increased
      surfactant protein A. Localization of proSP-C from lung sections prepared from
      this patient using immunofluorescence and immunogold electron microscopy revealed
      abnormal proSP-C staining in endosomal-like vesicles of type II cells distinct
      from SP-B. To evaluate the effect of the E66K substitution on intracellular
      trafficking of proSP-C, fusion proteins consisting of enhanced green fluorescent
      protein (EGFP) and hSP-C(1-197) (wild type) or mutant hSP-C(E66K) were generated
      and transfected into A549 cells. EGFP/hSP-C(1-197) was expressed within CD-63
      positive, EEA-1-negative vesicles, whereas EGFP/hSP-C(E66K) localized to EEA-1
      positive vesicles. The E66K substitution is representative of a new class of SP-C
      mutation associated with interstitial lung disease that is diverted from the
      normal biosynthetic pathway. We propose that, similar to other storage disorders,
      lung injury results from induction of a toxic gain of function induced by the
      mutant product that is subject to genetic modifiers and environmental influences.

PMID- 15557113
TI  - Upper airway dynamic responses in children with the obstructive sleep apnea
      syndrome.
AB  - Normal children have a smaller upper airway than adults, but, nevertheless, snore
      less and have less apnea. We have previously shown that normal children have an
      upper airway that is resistant to collapse during sleep. We hypothesized that
      this resistance to collapse is due to preservation of upper airway neuromotor
      responses during sleep. Furthermore, we hypothesized that upper airway responses
      would be diminished in children with the obstructive sleep apnea syndrome (OSAS).
      We therefore compared the upper airway pressure-flow relationship during sleep
      between children with OSAS and controls. Measurements were made by correlating
      maximal inspiratory airflow with the level of nasal pressure applied via a mask.
      Neuromotor upper airway activation was assessed by evaluating the upper airway
      response to 1) hypercapnia and 2) intermittent, acute negative pressure. We found
      that children with OSAS had no significant response to either hypercapnia or
      negative pressure during sleep, compared with the normal children. After
      treatment of OSAS by tonsillectomy and adenoidectomy, there was a trend for
      normalization of upper airway responses. We conclude that upper airway dynamic
      responses are decreased in children with OSAS but recover after treatment. We
      speculate that the pharyngeal airway neuromotor responses present in normal
      children are a compensatory response for a relatively narrow upper airway.
      Further, we speculate that this compensatory response is lacking in children with
      OSAS, most likely due to either habituation to chronic respiratory abnormalities
      during sleep or to mechanical damage to the upper airway.

PMID- 15557114
TI  - Vascular endothelial growth factor-A induces prenatal neovascularization and
      alters bronchial development in mice.
AB  - Pulmonary vascular development requires precise temporal and spatial expression
      of vascular endothelial growth factor-A (VEGF-A). Diminished expression of VEGF-A
      in preterm infants may contribute to the pathophysiology of respiratory distress
      syndrome. Because exogenous replacement of VEGF-A has been proposed as a
      therapeutic for respiratory distress syndrome, we used conditional activation of
      VEGF-A in bronchial epithelial cells to assess the effects of increase of VEGF-A
      on lung morphogenesis and survival in the developing mouse. Increased expression
      of VEGF-A in late stages of gestation was lethal at birth. Although born alive,
      the pups remained cyanotic and failed to establish respiration. Vascular and
      epithelial morphology of the main bronchus and primary and secondary bronchi were
      altered with neovascularization of the mucosal folds and partial obstruction of
      the conducting airways. Erythrocytes were observed in the pulmonary interstitium
      and in intra-alveolar spaces, indicating vascular leak. Increased diameter of
      pulmonary arteries and angioectatic structures were observed in VEGF-expressing
      mice. Bronchial expression of VEGF-A alters late-stage morphogenesis of
      conducting airways and primary bronchial arteries and causes respiratory failure
      at birth.

PMID- 15557115
TI  - The FG-repeat asymmetry of the nuclear pore complex is dispensable for bulk
      nucleocytoplasmic transport in vivo.
AB  - Nucleocytoplasmic transport occurs through gigantic proteinaceous channels called
      nuclear pore complexes (NPCs). Translocation through the NPC is exquisitely
      selective and is mediated by interactions between soluble transport carriers and
      insoluble NPC proteins that contain phenylalanine-glycine (FG) repeats. Although
      most FG nucleoporins (Nups) are organized symmetrically about the planar axis of
      the nuclear envelope, very few localize exclusively to one side of the NPC. We
      constructed Saccharomyces cerevisiae mutants with asymmetric FG repeats either
      deleted or swapped to generate NPCs with inverted FG asymmetry. The mutant Nups
      localize properly within the NPC and exhibit exchanged binding specificity for
      the export factor Xpo1. Surprisingly, we were unable to detect any defects in the
      Kap95, Kap121, Xpo1, or mRNA transport pathways in cells expressing the mutant FG
      Nups. These findings suggest that the biased distribution of FG repeats is not
      required for major nucleocytoplasmic trafficking events across the NPC.

PMID- 15557116
TI  - Structural and functional analysis of Nup133 domains reveals modular building
      blocks of the nuclear pore complex.
AB  - Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) whose
      complex architecture is generated from a set of only approximately 30 proteins,
      termed nucleoporins. Here, we explore the domain structure of Nup133, a
      nucleoporin in a conserved NPC subcomplex that is crucial for NPC biogenesis and
      is believed to form part of the NPC scaffold. We show that human Nup133 contains
      two domains: a COOH-terminal domain responsible for its interaction with its
      subcomplex through Nup107; and an NH2-terminal domain whose crystal structure
      reveals a seven-bladed beta-propeller. The surface properties and conservation of
      the Nup133 beta-propeller suggest it may mediate multiple interactions with other
      proteins. Other beta-propellers are predicted in a third of all nucleoporins.
      These and several other repeat-based motifs appear to be major elements of
      nucleoporins, indicating a level of structural repetition that may conceptually
      simplify the assembly and disassembly of this huge protein complex.

PMID- 15557117
TI  - Mlp-dependent anchorage and stabilization of a desumoylating enzyme is required
      to prevent clonal lethality.
AB  - Myosin-like proteins 1 and 2 (Mlp1 and Mlp2) form filaments attached to the
      nucleoplasmic side of the nuclear pore complexes via interaction with the
      nucleoporin Nup60. Here, we show that Mlps and Nup60, but not several other
      nucleoporins, are required to localize and stabilize a desumoylating enzyme Ulp1.
      Moreover, like Mlps, Ulp1 exhibits a unique asymmetric distribution on the
      nuclear envelope. Consistent with a role in regulating Ulp1, removal of either or
      both MLPs affects the SUMO conjugate pattern. We also show that deleting MLPs or
      the localization domains of Ulp1 results in DNA damage sensitivity and clonal
      lethality, the latter of which is caused by increased levels of 2-micron circle
      DNA. Epistatic and dosage suppression analyses further demonstrate that Mlps
      function upstream of Ulp1 in 2-micron circle maintenance and the damage response.
      Together, our results reveal that Mlps play important roles in regulating Ulp1
      and subsequently affect sumoylation stasis, growth, and DNA repair.

PMID- 15557118
TI  - Condensin restructures chromosomes in preparation for meiotic divisions.
AB  - The production of haploid gametes from diploid germ cells requires two rounds of
      meiotic chromosome segregation after one round of replication. Accurate meiotic
      chromosome segregation involves the remodeling of each pair of homologous
      chromosomes around the site of crossover into a highly condensed and ordered
      structure. We showed that condensin, the protein complex needed for mitotic
      chromosome compaction, restructures chromosomes during meiosis in Caenorhabditis
      elegans. In particular, condensin promotes both meiotic chromosome condensation
      after crossover recombination and the remodeling of sister chromatids. Condensin
      helps resolve cohesin-independent linkages between sister chromatids and
      alleviates recombination-independent linkages between homologues. The
      safeguarding of chromosome resolution by condensin permits chromosome segregation
      and is crucial for the formation of discrete, individualized bivalent
      chromosomes.

PMID- 15557119
TI  - Invadolysin: a novel, conserved metalloprotease links mitotic structural
      rearrangements with cell migration.
AB  - The cell cycle is widely known to be regulated by networks of phosphorylation and
      ubiquitin-directed proteolysis. Here, we describe IX-14/invadolysin, a novel
      metalloprotease present only in metazoa, whose activity appears to be essential
      for mitotic progression. Mitotic neuroblasts of Drosophila melanogaster IX-14
      mutant larvae exhibit increased levels of nuclear envelope proteins, monopolar
      and asymmetric spindles, and chromosomes that appear hypercondensed in length
      with a surrounding halo of loosely condensed chromatin. Zymography reveals that a
      protease activity, present in wild-type larval brains, is missing from homozygous
      tissue, and we show that IX-14/invadolysin cleaves lamin in vitro. The IX
      14/invadolysin protein is predominantly found in cytoplasmic structures
      resembling invadopodia in fly and human cells, but is dramatically relocalized to
      the leading edge of migrating cells. Strikingly, we find that the directed
      migration of germ cells is affected in Drosophila IX-14 mutant embryos. Thus,
      invadolysin identifies a new family of conserved metalloproteases whose activity
      appears to be essential for the coordination of mitotic progression, but which
      also plays an unexpected role in cell migration.

PMID- 15557120
TI  - Phosphorylation of DCC by Fyn mediates Netrin-1 signaling in growth cone
      guidance.
AB  - Netrin-1 acts as a chemoattractant molecule to guide commissural neurons (CN)
      toward the floor plate by interacting with the receptor deleted in colorectal
      cancer (DCC). The molecular mechanisms underlying Netrin-1-DCC signaling are
      still poorly characterized. Here, we show that DCC is phosphorylated in vivo on
      tyrosine residues in response to Netrin-1 stimulation of CN and that the Src
      family kinase inhibitors PP2 and SU6656 block both Netrin-1-dependent
      phosphorylation of DCC and axon outgrowth. PP2 also blocks the reorientation of
      Xenopus laevis retinal ganglion cells that occurs in response to Netrin-1, which
      suggests an essential role of the Src kinases in Netrin-1-dependent orientation.
      Fyn, but not Src, is able to phosphorylate the intracellular domain of DCC in
      vitro, and we demonstrate that Y1418 is crucial for DCC axon outgrowth function.
      Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(
      /-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine
      phosphorylation and that Fyn is essential for the response of axons to Netrin-1.

PMID- 15557121
TI  - Protein oligomerization modulates raft partitioning and apical sorting of GPI
      anchored proteins.
AB  - An essential but insufficient step for apical sorting of
      glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) in epithelial
      cells is their association with detergent-resistant microdomains (DRMs) or rafts.
      In this paper, we show that in MDCK cells both apical and basolateral GPI-APs
      associate with DRMs during their biosynthesis. However, only apical and not
      basolateral GPI-APs are able to oligomerize into high molecular weight complexes.
      Protein oligomerization begins in the medial Golgi, concomitantly with DRM
      association, and is dependent on protein-protein interactions. Impairment of
      oligomerization leads to protein missorting. We propose that oligomerization
      stabilizes GPI-APs into rafts and that this additional step is required for
      apical sorting of GPI-APs. Two alternative apical sorting models are presented.

PMID- 15557122
TI  - Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and
      impaired spermatogenesis.
AB  - Mutations in MTMR2, the myotubularin-related 2 gene, cause autosomal recessive
      Charcot-Marie-Tooth (CMT) type 4B1, a demyelinating neuropathy with myelin
      outfolding and azoospermia. MTMR2 encodes a ubiquitously expressed phosphatase
      whose preferred substrate is phosphatidylinositol (3,5)-biphosphate, a regulator
      of membrane homeostasis and vesicle transport. We generated Mtmr2-null mice,
      which develop progressive neuropathy characterized by myelin outfolding and
      recurrent loops, predominantly at paranodal myelin, and depletion of spermatids
      and spermatocytes from the seminiferous epithelium, which leads to azoospermia.
      Disruption of Mtmr2 in Schwann cells reproduces the myelin abnormalities. We also
      identified a novel physical interaction in Schwann cells, between Mtmr2 and discs
      large 1 (Dlg1)/synapse-associated protein 97, a scaffolding molecule that is
      enriched at the node/paranode region. Dlg1 homologues have been located in
      several types of cellular junctions and play roles in cell polarity and membrane
      addition. We propose that Schwann cell-autonomous loss of Mtmr2-Dlg1 interaction
      dysregulates membrane homeostasis in the paranodal region, thereby producing
      outfolding and recurrent loops of myelin.

PMID- 15557123
TI  - SPOTS: signaling protein oligomeric transduction structures are early mediators
      of death receptor-induced apoptosis at the plasma membrane.
AB  - Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly
      triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis
      and prevention of autoimmunity. Although FADD and caspase-8 have been identified
      as key intracellular mediators of Fas signaling, it is not clear how recruitment
      of these proteins to the Fas death domain leads to activation of caspase-8 in the
      receptor signaling complex. We have used high-resolution confocal microscopy and
      live cell imaging to study the sequelae of early events in Fas signaling. These
      studies have revealed a new stage of Fas signaling in which receptor ligation
      leads to the formation of surface receptor oligomers that we term signaling
      protein oligomerization transduction structures (SPOTS). Formation of SPOTS
      depends on the presence of an intact Fas death domain and FADD but is independent
      of caspase activity. Analysis of cells expressing Fas mutations from patients
      with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of
      SPOTS can be disrupted by distinct mechanisms in ALPS.

PMID- 15557124
TI  - Integrin alphav-mediated inactivation of p53 controls a MEK1-dependent melanoma
      cell survival pathway in three-dimensional collagen.
AB  - Integrin alphav is required for melanoma cell survival and tumor growth in
      various models. To elucidate integrin alphav-mediated melanoma cell survival
      mechanisms, we used a three-dimensional (3D) collagen gel model mimicking the
      pathophysiological microenvironment of malignant melanoma in the dermis. We found
      that integrin alphav inactivated p53 and that suppression of p53 activity by
      dominant negative p53 or p53-small interfering RNA obviated the need for integrin
      alphav for melanoma cell survival in 3D-collagen and for tumor growth in vivo.
      This indicates that integrin alphav-mediated inactivation of p53 functionally
      controls melanoma cell survival. Furthermore, we found that melanoma cell
      integrin alphav was required for MAPK kinase (MEK) 1 and extracellular signal
      regulated kinase (ERK)1/2 activity in 3D-collagen, whereas inhibition of MEK1
      activity induced apoptosis. Surprisingly, MEK1 and ERK1/2 activities were
      restored in integrin alphav-negative melanoma cells by suppression of p53,
      whereas concomitant block of MEK1 induced apoptosis. This suggests that integrin
      alphav controls melanoma cell survival in 3D-collagen through a pathway involving
      p53 regulation of MEK1 signaling.

PMID- 15557125
TI  - Tumor cell traffic through the extracellular matrix is controlled by the membrane
      anchored collagenase MT1-MMP.
AB  - As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and
      intravasate, they adopt a fibroblast-like phenotype and engage undefined
      proteolytic cascades that mediate invasive activity. Herein, we find that
      fibroblasts and cancer cells express an indistinguishable pericellular
      collagenolytic activity that allows them to traverse the ECM. Using fibroblasts
      isolated from gene-targeted mice, a matrix metalloproteinase (MMP)-dependent
      activity is identified that drives invasion independently of plasminogen, the
      gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or
      stromelysin-1. In contrast, deleting or suppressing expression of the membrane
      tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of
      collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as
      the major cell-associated proteinase necessary to confer normal or neoplastic
      cells with invasive activity.

PMID- 15557126
TI  - Drosophila paramyosin is important for myoblast fusion and essential for
      myofibril formation.

PMID- 15557128
TI  - Pharmacogenetic differences in response to albuterol between Puerto Ricans and
      Mexicans with asthma.
AB  - BACKGROUND: In the United States, Puerto Ricans and Mexicans have the highest and
      lowest asthma prevalence, morbidity, and mortality, respectively. Ethnic-specific
      differences in the response to drug treatment may contribute to differences in
      disease outcomes. Genetic variants at the beta(2)-adrenergic receptor (beta(2)AR)
      may modify asthma severity and albuterol responsiveness. We tested the
      association of beta(2)AR genotypes with asthma severity and bronchodilator
      response to albuterol in Puerto Ricans and Mexicans with asthma. METHODS: We used
      both family-based and cross-sectional tests of association with 8 beta(2)AR
      single nucleotide polymorphisms in 684 Puerto Rican and Mexican families.
      Regression analyses were used to determine the interaction between genotype,
      asthma severity, and bronchodilator drug responsiveness. RESULTS: Among Puerto
      Ricans with asthma, the arginine (Arg) 16 allele was associated with greater
      bronchodilator response using both family-based and cross-sectional tests (p =
      0.00001-0.01). We found a strong interaction of baseline FEV(1) with the
      Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among
      Puerto Ricans with asthma with baseline FEV(1) < 80% of predicted, but not in
      those with FEV(1) > 80%, there was a very strong association between the Arg16
      genotype and greater bronchodilator responsiveness. No association was observed
      between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma.
      CONCLUSIONS: Ethnic-specific pharmacogenetic differences exist between Arg16Gly
      genotypes, asthma severity, and bronchodilator response in Puerto Ricans and
      Mexicans with asthma. These findings underscore the need for additional research
      on racial/ethnic differences in asthma morbidity and drug responsiveness.

PMID- 15557129
TI  - Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide
      attenuates asthma in mice.
AB  - The p38 mitogen-activated protein kinase (MAPK) plays a critical role in the
      activation of inflammatory cells. Therefore, we investigated the antiinflammatory
      effects of a respirable p38alpha MAPK antisense oligonucleotide (p38alpha-ASO) in
      a mouse asthma model. A potent and selective p38alpha-ASO was characterized in
      vitro. Inhalation of aerosolized p38alpha-ASO using an aerosol chamber dosing
      system produced measurable lung deposition of ASO and significant reduction of
      ovalbumin (OVA-)-induced increases in total cells, eosinophils, and interleukin 4
      (IL-4), IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and dose
      dependent inhibition of airway hyperresponsiveness in allergen-challenged mice.
      Furthermore, inhaled p38alpha-ASO markedly inhibited OVA-induced lung tissue
      eosinophilia and airway mucus hypersecretion. Quantitative polymerase chain
      reaction analysis of bronchoalveolar lavage fluid cells and peribronchial lymph
      node cells showed that p38alpha-ASO significantly reduced p38alpha MAPK mRNA
      expression. Nose-only aerosol exposure of mice verified the p38alpha-ASO-induced
      inhibition of OVA-induced pulmonary eosinophilia, mucus hypersecretion, and
      airway hyperresponsiveness. None of the effects of the p38alpha-ASO were produced
      by a six-base mismatched control oligonucleotide. These findings demonstrate
      antisense pharmacodynamic activity in the airways after aerosol delivery and
      suggest that a p38alpha MAPK ASO approach may have therapeutic potential for
      asthma and other inflammatory lung diseases.

PMID- 15557130
TI  - Morning levels of C-reactive protein in children with obstructive sleep
      disordered breathing.
AB  - Obstructive sleep-disordered breathing is associated with cardiovascular disease
      in adults, and elevated C-reactive protein (CRP) has been proposed as a link
      between the two disorders. We hypothesized that children with sleep-disordered
      breathing have higher CRP values than do control subjects. CRP was measured in 39
      children (mean age +/- SD: 6.9 +/- 3.2 years) without snoring (controls) and in
      102 children (6.2 +/- 2.2 years) with habitual snoring who underwent
      polysomnography. No significant differences were found in mean CRP values between
      control subjects (0.12 +/- 0.16 mg/dl; n = 39) and snorers with an apnea-hypopnea
      index of less than 1 episode/hour (0.15 +/- 0.26; n = 18), snorers with an index
      of 1 or more and less than 5 (0.15 +/- 0.26; n = 54), and snorers with an index
      of 5 or more (0.22 +/- 0.43; n = 30; p > 0.05). There was no correlation between
      CRP or log-transformed CRP values and apnea-hypopnea index, respiratory
      movement/arousal index, Sa(O(2)) nadir, oxygen desaturation (>/= 4%) of
      hemoglobin index, or percentage of sleep time with saturation less than 95% (p >
      0.05). Thus, findings of higher CRP values in adults with sleep-disordered
      breathing and correlations of these values with polysomnography indices were not
      confirmed in children.

PMID- 15557131
TI  - Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary
      randomized study.
AB  - We hypothesize that hydrocortisone infusion in severe community-acquired
      pneumonia attenuates systemic inflammation and leads to earlier resolution of
      pneumonia and a reduction in sepsis-related complications. In a multicenter
      trial, patients admitted to the Intensive Care Unit (ICU) with severe community
      acquired pneumonia received protocol-guided antibiotic treatment and were
      randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given
      as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7
      days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2))
      (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ
      dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic
      shock. Forty-six patients entered the study. At study entry, the hydrocortisone
      group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C
      reactive protein level. By Study Day 8, treated patients had, compared with
      control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and
      chest radiograph score (p < 0.0001), and a significant reduction in C-reactive
      protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p =
      0.001). Hydrocortisone treatment was associated with a significant reduction in
      length of hospital stay (p = 0.03) and mortality (p = 0.009).

PMID- 15557132
TI  - Behavior problems antecede the development of wheeze in childhood: a birth cohort
      study.
AB  - RATIONALE: It is not clear to what extent behavior problems observed in children
      with asthma antecede asthma development, or are a consequence of the disease.
      OBJECTIVES: We investigated psychologic factors at age 3 years and subsequent
      development of wheeze by age 5 in an unselected birth cohort study. Children were
      recruited prenatally, followed prospectively, and reviewed at age 3 and 5 years.
      The rate of significant behavior problems at age 3 (above the clinically relevant
      cut-off on the Eyberg Child Behavior Inventory) was compared between children who
      had never wheezed (n = 397) and those developing late-onset wheezing (after age 3
      years; n = 39). Late-onset wheezers were more likely to be above cut-offs for
      behavior problems at 3 years (before wheeze onset), compared with children who
      never wheezed, on Intensity (23.1% vs. 6.0%, p < 0.001) and Problem scores (10.8%
      vs. 1.3%, p < 0.001). Families of late-onset wheezers had poorer scores on family
      functioning variables, but we found no evidence of increased anxiety or
      depression scores in parents. In the multivariate analysis, significant and
      independent associates of late-onset wheeze were as follows: maternal asthma
      (odds ratio [OR] 5.4, 95% confidence intervals [CI] 2.1-13.8, p < 0.001),
      maternal smoking when child was 3 years (OR 3.3, CI 1.2-8.7, p = 0.02),
      expressiveness (OR 0.71, CI 0.55-0.9, p = 0.005), and significant behavior
      problems at age 3 years (OR 3.5, CI 1.2-9.9, p = 0.02). CONCLUSIONS: Behavior
      problems in early life are associated with increased risk of subsequent
      development of wheeze.

PMID- 15557133
TI  - Lung inflammation and fibrosis: an alveolar macrophage-centered perspective from
      the 1970s to 1980s.

PMID- 15557134
TI  - Asthma severity is associated with body mass index and early menarche in women.
AB  - Asthma severity in relation to body mass index (BMI) has rarely been studied. The
      relation between BMI and asthma severity was studied by sex in 366 adults with
      asthma from the Epidemiological Study on the Genetics and Environment of Asthma,
      a case-control and family study on asthma. Factors related to asthma severity and
      BMI such as smoking, FEV(1), bronchial hyperresponsiveness, and dyspnea were
      taken into account. The influence of early menarche was studied to assess the
      potential role of hormonal factors. Clinical asthma severity in the last 12
      months was assessed by a score (0-7) based on the frequency of asthma attacks,
      persisting symptoms between attacks, and hospitalization. Asthma severity, which
      was unrelated to sex, increased with BMI in women (p = 0.0001) but not in men (p
      = 0.3). In women, the association remained after adjustment for age, FEV(1),
      smoking habits, and BMI-adjusted dyspnea and taking into account familial
      dependence (p = 0.0001). The association between BMI and severity was stronger in
      women with early menarche than in women without early menarche (p interaction =
      0.02). Findings support the hypothesis of hormonal factors involved in the
      severity of asthma.

PMID- 15557135
TI  - Sex differences in the relation between body mass index and asthma and atopy in a
      birth cohort.
AB  - RATIONALE: Several studies have identified an association between asthma and
      obesity in women. It remains unclear if this association is due to genuine asthma
      or to symptoms caused by overweight, at what age the association develops, and
      whether it is confined to females. OBJECTIVE: To explore the relations between
      body mass index, asthma, and atopy in a birth cohort of approximately 1,000
      individuals. METHODS: Information on asthma and measurements of lung function,
      airway responsiveness, and atopy were obtained on multiple occasions between ages
      9 and 26. Associations between these outcomes and body mass index were analyzed
      using generalized mixed linear regression models. Further analyses adjusted for
      potential covariates including breastfeeding, birth order, parental asthma, and
      personal and family smoking history. MAIN RESULTS: Body mass index was positively
      associated with asthma, wheeze, asthma treatment, atopy, immunoglobulin E, and
      inversely with the FEV(1)/FVC ratio in females. There was no significant
      association with airway responsiveness to methacholine or salbutamol. There was
      little evidence of an association between body mass index and asthma or atopy in
      males. Analyses adjusting for potential covariates showed similar findings.
      Asthma was not associated with a raised body mass index in childhood and
      childhood asthma did not lead to being overweight as an adult. CONCLUSIONS: A
      raised body mass index is associated with asthma and atopy in women but not men.
      Population attributable fraction calculations estimate that 28% (95% confidence
      interval 7-45) of asthma developing in women after age 9 is due to overweight.

PMID- 15557136
TI  - Effects of carbon monoxide inhalation during experimental endotoxemia in humans.
AB  - Data show that carbon monoxide (CO) exerts direct antiinflammatory effects in
      vitro and in vivo after LPS challenge in a mouse model. We hypothesized that CO
      may act as an antiinflammatory agent in human endotoxemia. The aim of this trial
      was to study the effects of CO inhalation on cytokine production during
      experimental human endotoxemia. The main study was a randomized, double-blinded,
      placebo-controlled, two-way cross-over trial in healthy volunteers. Each
      volunteer inhaled synthetic air (as placebo) and 500 ppm CO for 1 hour in random
      order with a washout period of 6 weeks and received a 2-ng/kg intravenous bolus
      of LPS after inhalation. Carboxyhemoglobin levels were assessed as a safety
      parameter. CO inhalation increased carboxyhemoglobin levels from 1.2% (95%
      confidence interval, 1.0 to 1.4%) to peak values of 7.0% (95% confidence
      interval, 6.5 to 7.7%). LPS infusion transiently increased plasma concentrations
      of tumor necrosis factor-alpha, interleukin (IL)-6 (approximately 150-fold
      increases), and IL-8, as well as IL-1alpha and IL-1beta mRNA levels (an
      approximately 200-fold increase). These LPS-induced changes were not influenced
      by CO inhalation. Inhalation of 500 ppm CO for 1 hour had no antiinflammatory
      effects in a systemic inflammation model in humans, as 250 ppm for 1 hour did in
      rodents.

PMID- 15557137
TI  - Multiple genes, one polypeptide chain.

PMID- 15557138
TI  - An immunoglobulin heavy chain variable region gene is generated from three
      segments of DNA: VH, D and JH. 1980.

PMID- 15557139
TI  - The fourth way? Harnessing aggressive tendencies in the thymus.
AB  - During late stages of thymic development, T cells must chose between different
      fates, dictated by their TCR specificity. Typically, this is thought of as a
      choice between three alternatives (being positive selection for useful T cells vs
      negative selection or neglect for harmful or useless T cells). However, there is
      growing evidence for a fourth alternative, in which T cells are positively
      selected by agonist ligands, which would normally be expected to induce T cell
      deletion. In this review, we will discuss where and when agonist selection is
      induced and whether this should be considered as a novel form of thymic selection
      or as an alternative differentiation state for Ag-exposed T cells.

PMID- 15557140
TI  - Cutting edge: neutrophil granulocyte serves as a vector for Leishmania entry into
      macrophages.
AB  - Macrophages (MF) are the final host cells for multiplication of the intracellular
      parasite Leishmania major (L. major). However, polymorphonuclear neutrophil
      granulocytes (PMN), not MF, are the first leukocytes that migrate to the site of
      infection and encounter the parasites. Our previous studies indicated that PMN
      phagocytose but do not kill L. major. Upon infection with Leishmania, apoptosis
      of human PMN is delayed and takes 2 days to occur. Infected PMN were found to
      secrete high levels of the chemokine MIP-1beta, which attracts MF. In this study,
      we investigated whether MF can ingest parasite-infected PMN. We observed that MF
      readily phagocytosed infected apoptotic PMN. Leishmania internalized by this
      indirect way survived and multiplied in MF. Moreover, ingestion of apoptotic
      infected PMN resulted in release of the anti-inflammatory cytokine TGF-beta by
      MF. These data indicate that Leishmania can misuse granulocytes as a "Trojan
      horse" to enter their final host cells "silently" and unrecognized.

PMID- 15557141
TI  - Cutting edge: TGF-beta signaling is required for the in vivo expansion and
      immunosuppressive capacity of regulatory CD4+CD25+ T cells.
AB  - Data regarding the role of TGF-beta for the in vivo function of regulatory
      CD4(+)CD25(+) T cells (Treg) are controversial. A transgenic mouse model with
      impaired TGF-beta signaling specifically in T cells was used to assess the role
      of endogenous TGF-beta for the in vivo function of CD4(+)CD25(+) Treg in a murine
      model of colitis induced by dextran sulfate. Transfer of wild-type, but not
      transgenic CD4(+)CD25(+) Treg was found to suppress colitis in wild-type mice. In
      addition, by transferring CFSE-labeled CD4(+)CD25(+) Treg we could demonstrate
      that endogenous TGF-beta promotes the expansion of CD4(+)CD25(+) Treg in vivo.
      Transgenic mice themselves developed reduced numbers of peripheral CD4(+)CD25(+)
      Treg and were more susceptible to the induction of colitis, which could be
      prevented by the transfer of wild-type Treg. These data indicate that TGF-beta
      signaling in CD4(+)CD25(+) Treg is required for their in vivo expansion and
      suppressive capacity.

PMID- 15557142
TI  - Cutting edge: TCR revision occurs in germinal centers.
AB  - Mouse CD4(+)Vbeta5(+) T cells recognize a peripherally expressed superantigen
      encoded by an endogenous retrovirus. Ag encounter tolerizes the mature CD4 T cell
      compartment, either by deletion of autoreactive cells or by TCR revision. This
      latter process is driven by TCRbeta rearrangement through RAG activity and
      results in the rescue of cells expressing novel TCRs that no longer recognize the
      tolerogen. Consistent with the notion that revising T cells represent a distinct
      peripheral T cell population, we now show that these lymphocyte blasts express a
      hybrid effector/memory phenotype and are not undergoing cell division. A
      population of revising T cells is CD40(+), expresses the germinal center (GC)
      marker CXCR5, and is Vbeta5(low)Thy-1(low). Histology reveals that, consistent
      with their surface Ag phenotype, T cells undergoing TCR revision are enriched in
      splenic GCs. These data demonstrate that TCR revision is a multistep tolerance
      pathway supported by the unique microenvironment provided by GCs.

PMID- 15557143
TI  - Cutting edge: transpresentation of IL-15 by bone marrow-derived cells
      necessitates expression of IL-15 and IL-15R alpha by the same cells.
AB  - IL-15 is critical for generation of multiple lymphoid subsets. Recent data have
      demonstrated a unique aspect of responses to IL-15, in that cells bearing the IL
      15Ralpha chain can bind soluble IL-15 and "transpresent" the cytokine to other
      cells, allowing the latter to respond to IL-15. However, it is unclear whether IL
      15 is normally secreted and then becomes bound to surface IL-15Ralpha on
      bystander cells, or whether transpresentation is mediated by the same cells which
      synthesize IL-15. Using mixed bone marrow chimeric mice, we present evidence for
      the latter model, showing that development of NK cells and memory phenotype CD8 T
      cells necessitates that both IL-15 and IL-15Ralpha be expressed by the same
      population of cells. These data argue that soluble forms of IL-15 are irrelevant
      for physiological responses to this cytokine, and the implications of this
      finding are discussed.

PMID- 15557144
TI  - Cutting edge: a critical role for CD70 in CD8 T cell priming by CD40-licensed
      APCs.
AB  - The CD154/CD40 interaction is an important pathway of CD4 T cell help for CD8 T
      cell responses. In this study, we address the role of CD70, a member of the TNF
      superfamily and the ligand for the T cell costimulatory receptor CD27, in CD40
      mediated priming of CD8 T cells. Using an agonistic anti-CD40 mAb to mimic the
      CD154/CD40 interaction we demonstrate that the priming of OT-I TCR transgenic or
      endogenous mouse OVA-specific CD8 T cells is critically dependent on CD70/CD27
      interaction. CD70 blockade inhibited CD40-mediated clonal expansion of CD8 T
      cells and reduced the number of memory CD8 T cells generated. Furthermore, CD70
      blockade during the initial priming of CD8 T cells inhibited the ability of
      memory CD8 T cells to expand in response to a second encounter with Ag. Our data
      indicate that CD70 expression on APCs plays a key role in CD40-dependent CD8 T
      cell responses.

PMID- 15557145
TI  - Novel insights on human NK cells' immunological modalities revealed by gene
      expression profiling.
AB  - As part of the innate immune system, human NK cells play a critical role early in
      the systemic host defense against pathogens and tumor cells. Recent studies
      suggest a more complex view of NK cell behavior, as different functions and
      tissue localizing capabilities seem to be preferentially assigned to distinct
      subpopulations of NK cells, CD56(dim)CD16(+) or CD56(bright)CD16(-). In this
      study, we used oligonucleotide microarrays to compare the expression profile of
      approximately 20,000 genes in three NK cell subpopulations: peripheral blood
      derived CD56(dim)CD16(+), CD56(bright)CD16(-), and in vitro-activated CD16(+) NK
      cells. The differential expression of selected genes was verified by flow
      cytometry and functional assays. When comparing CD56(dim)CD16(+) and
      CD56(bright)CD16(-) subsets, a new heterogeneous molecular basis for the
      functional and developmental differences between these two subsets was revealed.
      Furthermore, systematic analysis of transcriptional changes in activated CD16(+)
      NK cells provided us with a better understanding of NK function in inflamed
      tissues. We highlight a number of genes that were overexpressed upon activation
      (e.g., OX40 ligand, CD86, Tim3, galectins, etc.), that enable these cells to
      directly cross-talk with other innate and adaptive immune effectors. The
      overexpressed genes assign novel intriguing immunomodulatory functions to
      activated NK cells, in addition to their potent cytotoxic abilities.

PMID- 15557146
TI  - The solvent-inaccessible Cys67 residue of HLA-B27 contributes to T cell
      recognition of HLA-B27/peptide complexes.
AB  - Crystallographic studies have suggested that the cysteine at position 67
      (Cys(67)) in the B pocket of the MHC molecule HLA-B*2705 is of importance for
      peptide binding, and biophysical studies have documented altered thermodynamic
      stability of the molecule when Cys(67) was mutated to serine (Ser(67)). In this
      study, we used HLA-B27.Cys(67) and HLA-B27.Ser(67) tetramers with defined T cell
      epitopes to determine the contribution of this polymorphic, solvent-inaccessible
      MHC residue to T cell recognition. We generated these HLA-B27 tetramers using
      immunodominant viral peptides with high binding affinity to HLA-B27 and cartilage
      derived peptides with lower affinity. We demonstrate that the yield of refolding
      of HLA-B27.Ser(67) molecules was higher than for HLA-B27.Cys(67) molecules and
      strongly dependent on the affinity of the peptide. T cell recognition did not
      differ between HLA-B27.Cys(67) and HLA.B27.Ser(67) tetramers for the viral
      peptides that were investigated. However, an aggrecan peptide-specific T cell
      line derived from an HLA-B27 transgenic BALB/c mouse bound significantly stronger
      to the HLA-B27.Cys(67) tetramer than to the HLA-B27.Ser(67) tetramer. Modeling
      studies of the molecular structure suggest the loss of a SH ... pi hydrogen bond
      with the Cys-->Ser substitution in the HLA-B27 H chain which reduces the
      stability of the HLA-B27/peptide complex. These results demonstrate that a
      solvent-inaccessible residue in the B pocket of HLA-B27 can affect TCR binding in
      a peptide-dependent fashion.

PMID- 15557147
TI  - "Pruning" of alloreactive CD4+ T cells using 5- (and 6-)carboxyfluorescein
      diacetate succinimidyl ester prolongs skin allograft survival.
AB  - Removal of alloreactive cells by either thymic deletion or deletion/anergy in the
      periphery is regarded as crucial to the development of tolerance. Dyes, such as
      CFSE, that allow monitoring of cell division suggest that in vitro proliferation
      could be a used as a way of "pruning" alloreactive cells while retaining a normal
      immune repertoire with retention of memory to previously encountered pathogens.
      This would overcome the problems occurring as a result of therapies that use
      massive depletion of T cells to allow acceptance of organ transplants or bone
      marrow grafts. We therefore used a skin graft model of CD4-mediated T cell
      rejection across a major H-2 mismatch (C57BL/6 (H-2(b)) to BALB/c (H-2(d)) mice)
      to evaluate whether nondividing CD4(+) T cells derived from a mixed lymphocyte
      culture would exhibit tolerance to a skin graft from the initial stimulator
      strain. We demonstrate that selective removal of dividing alloreactive CD4(+) T
      cells resulted in marked specific prolongation of allogeneic skin graft survival,
      and that the nondividing CD4(+) T cells retained a broad TCR repertoire and the
      ability to maintain memory. This novel way of depleting alloreactive T cells may
      serve as a useful strategy in combination with other mechanisms to achieve
      transplant tolerance.

PMID- 15557148
TI  - Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast
      progenitors.
AB  - Pax5 encodes BSAP, a member of the paired box domain transcription factors, whose
      expression is restricted to B lymphocyte lineage cells. Pax5(-/-) mice have a
      developmental arrest of the B cell lineage at the pro-B cell stage. We show here
      that Pax5(-/-) mice are severely osteopenic, missing 60% of their bone mass. The
      osteopenia can be accounted for by a >100% increase in the number of osteoclasts
      in bone measured histomorphometrically. This is not due to a lack of B cells,
      because other strains of B cell-deficient mice do not exhibit this phenotype.
      There was no difference in the number of osteoclasts produced in vitro by wild
      type and Pax5(-/-) bone marrow cells. In contrast, spleen cells from Pax5(-/-)
      mice produce as much as five times the number of osteoclasts as control spleen
      cells. Culture of Pax5(-/-) spleen cells yields a population of adherent cells
      that grow spontaneously in culture without added growth factors for >4 wk. These
      cells have a monocyte phenotype, produce large numbers of osteoclasts when
      induced in vitro, and therefore are highly enriched in osteoclast precursors.
      These data demonstrate a previously unsuspected connection between B cell and
      osteoclast development and a key role for Pax5 in the control of osteoclast
      development.

PMID- 15557149
TI  - Plasmacytoid dendritic cell recruitment by immobilized CXCR3 ligands.
AB  - Plasmacytoid dendritic cells (pDCs) recognize microbes, viruses in particular,
      and provide unique means of innate defense against them. The mechanism of pDC
      tissue recruitment remained enigmatic because the ligands of CXCR3, the cardinal
      chemokine receptor on pDCs, have failed to induce in vitro chemotaxis of pDCs in
      the absence of additional chemokines. In this study, we demonstrate that CXCR3 is
      sufficient to induce pDC migration, however, by a migratory mechanism that
      amalgamates the features of haptotaxis and chemorepulsion. To mediate
      "haptorepulsion" of pDCs, CXCR3 requires the encounter of its cognate ligands
      immobilized, optimally by heparan sulfate, in a form of a negative gradient. This
      is the first report of the absolute requirement of chemokine immobilization and
      presentation for its in vitro promigratory activity. The paradigmatic example of
      pDC haptorepulsion described here may represent a new pathophysiologically
      relevant migratory mechanism potentially used by other cells in response to other
      chemokines.

PMID- 15557150
TI  - Early and quantal (by litter) expression of insulin autoantibodies in the
      nonobese diabetic mice predict early diabetes onset.
AB  - Aiming to study the early stages of type 1 diabetes phenotype, before insulitis
      appears, we measured insulin autoantibodies (IAA) between 3 and 5 wk of age in
      the NOD mouse (early-IAA (E-IAA)). We report that IAA are found as early as at 3
      wk of age, at weaning, and their expression is a quantal phenotype. Maternal
      autoantibody status influences this early phenotype, because animals of litters
      issued from IAA-positive ante partum mothers develop E-IAA with a significantly
      higher incidence than animals issued from IAA-negative mothers. These E-IAA
      represent synthesized rather than transplacental autoantibodies, as evidenced by
      higher levels in many offspring compared with maternal IAA, and negative as well
      as positive offspring in the same litters and it correlates with early diabetes
      onset, defining the first autoimmune window in diabetes pathogenesis. Therefore,
      autoimmune processes leading to type 1 diabetes initiate early in life, are
      influenced by maternal autoantibody status, and can be revealed by the presence
      of IAA. Our data suggest that the mechanisms responsible for the breakdown of
      self-tolerance are subjected not only to genetic predisposition, but also to the
      physiological status of the mother. Pathological progression to autoimmunity is
      marked by the presence of immunological windows relating early steps with final
      disease onset.

PMID- 15557151
TI  - The contraction phase of virus-specific CD8+ T cells is unaffected by a pan
      caspase inhibitor.
AB  - The effectiveness of protection conferred by CD8(+) memory T cells is determined
      by both their quality and their quantity, which suggests that vaccine efficacy
      might be improved if it were possible to increase the size of the memory pool.
      Approximately 90% of virus-specific CD8(+) T cells die during the contraction
      phase and, herein, we have attempted to increase the memory pool by reducing
      CD8(+) T cell death. CD8(+) T cell contraction has been attributed to apoptosis,
      or programmed cell death (PCD), which, classically, is dependent on caspases.
      Caspase-dependent PCD can be prevented by the pan-caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone (zVAD), and here we
      evaluate the effect of this compound on virus-specific T cell responses in mice.
      zVAD prevented caspase-dependent PCD of freshly isolated virus-specific T cells
      in tissue culture, and a fluorescent analog, FITC-VAD, entered CD8(+) T cells
      following in vivo injection. However, despite using 11 different regimens of zVAD
      administration in vivo, no significant effects on CD8(+) or CD4(+) memory T cell
      numbers were observed. Furthermore, the CD8(+) memory T cell responses to
      secondary virus infection were indistinguishable, both qualitatively and
      quantitatively, in zVAD-treated and normal mice. The absence of effect cannot be
      attributed to a technical flaw, because identical doses of zVAD were able to
      rescue mice from hepatocyte apoptosis and lethal intrahepatic hemorrhage, induced
      by inoculation of anti-Fas Ab. We conclude that the contraction phase of the
      virus-specific T cell response is unlikely to require caspase-dependent PCD. We
      propose that contraction can be mediated by an alternative, caspase-independent
      pathway(s).

PMID- 15557152
TI  - Cellular FLIP (long isoform) overexpression in T cells drives Th2 effector
      responses and promotes immunoregulation in experimental autoimmune
      encephalomyelitis.
AB  - Cellular FLIP (c-FLIP) is an endogenous inhibitor of death receptor-induced
      apoptosis through the caspase 8 pathway. It is an NF-kappaB-inducible protein
      thought to promote the survival of T cells upon activation, and its down
      regulation has been implicated in activation-induced cell death. We have
      generated transgenic mice overexpressing human c-FLIP long form (c-FLIP(L))
      specifically in T cells using the CD2 promoter (TgFLIP(L)). TgFLIP(L) mice
      exhibit increased IgG1 production upon stimulation by a T cell-dependent Ag and a
      markedly enhanced contact hypersensitivity response to allergen. In addition to
      showing augmented Th2-type responses, TgFLIP(L) mice are resistant to the
      development of myelin oligodendrocyte glycoprotein 35-55 peptide-induced
      experimental autoimmune encephalomyelitis, a Th1-driven autoimmune disease. In
      vitro analyses revealed that T cells of TgFLIP(L) mice proliferate normally, but
      produce higher levels of IL-2 and show preferential maturation of Th2 cytokine
      producing cells in response to antigenic stimulation. After adoptive transfer,
      these (Th2) cells protected wild-type recipient mice from experimental autoimmune
      encephalomyelitis induction. Our results show that the constitutive
      overexpression of c-FLIP(L) in T cells is sufficient to drive Th2 polarization of
      effector T cell responses and indicate that it might function as a key regulator
      of Th cell differentiation.

PMID- 15557153
TI  - Following immunization antigen becomes concentrated in a limited number of APCs
      including B cells.
AB  - Immunization with the hen egg-white lysozyme (HEL) protein induces T cells to
      various of its peptide determinants. The distribution of such T cells, however,
      does not correlate with the peptide level of each epitope on class II molecules.
      For this reason, we sought information on the cells responsible for Ag
      presentation following immunization, hoping to understand the lack of
      immunodominance in this system. By tracking HEL, and the ensuing peptide/MHC
      complexes, we find the following: 1) that HEL in the draining lymph node gets
      concentrated in a limited number of APC, particularly in dendritic cells and
      macrophages, 2) that these APC are functionally capable of presenting both major
      and minor determinants of HEL over a 100-fold range of Ag dose, and 3) that B
      cells present Ag gained at early times after immunization, but only following
      higher dose immunization. These data indicate that the breadth of a response is
      maintained over a wide dosage range by concentration of Ag in a limited number of
      cells presenting high levels and a great diversity of epitopes.

PMID- 15557154
TI  - IL-12 gene therapy is an effective therapeutic strategy for hepatocellular
      carcinoma in immunosuppressed mice.
AB  - Immunosuppressive therapy for organ transplantation is essential for controlling
      rejection. When liver transplantation is performed as a therapy for
      hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal
      complications. In this study, we show that intratumoral murine IL-12 (mIL-12)
      gene therapy has the potential to be an effective treatment for malignancies
      under immunosuppression. C3H mice (H-2(k)), injected with FK506 (3 mg/kg) i.p.,
      were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the
      established HCC with electroporation-mediated gene therapy using mIL-12 plasmid
      DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN
      gamma, and IFN-gamma-inducible protein-10, significantly reduced the number of
      microvessels and inhibited the growth of HCC, compared with HCC-transferred
      control pCAGGS plasmid. The inhibition of tumor growth in immunosuppressed mice
      was comparable with that of mIL-12 gene therapy in immunocompetent mice.
      Intratumoral mIL-12 gene therapy enhanced lymphocytic infiltration into the tumor
      and elicited the MH134-specific CTL response even under FK506. The dose of FK506
      was sufficient to prevent the rejection of distant allogenic skin grafts (BALB/c
      mice, H-2(d)) and tumors, B7-p815 (H-2(d)) used as transplants, during mIL-12
      gene therapy against MH134. Ab-mediated depletion studies suggested that the
      inhibition of tumor growth, neovascularization, and spontaneous lung metastasis
      by mIL-12 was dependent almost entirely on NK cells and partially on T cells.
      These results suggest that intratumoral mIL-12 gene therapy is a potent effective
      strategy not only to treat recurrences of HCC in liver transplantation, but also
      to treat solid malignant tumors in immunosuppressed patients with transplanted
      organ.

PMID- 15557155
TI  - Role of CTLA-4 in the activation of single- and double-positive thymocytes.
AB  - CTLA-4, a homologue of CD28, is a negative regulator of T cell activation in the
      periphery and is transiently expressed on the cell surface after T cell
      activation. However, the role of CTLA-4 in T cell activation in the thymus is not
      clear. This investigation was initiated to determine the role of CTLA-4 in the
      activation of CD4(+)CD8(+) double-positive (DP) and CD4(+)CD8(-) and CD4(-)CD8(+)
      single-positive (SP) thymocytes using fetal thymic organ cultures (FTOC) of MHC
      class II-restricted, OVA(323-339)-restricted TCR transgenic mice (DO11.10). We
      found that treatment of the FTOC with anti-CTLA-4-blocking Ab during activation
      with OVA(323-339) increased the proportion and number of DP thymocytes, but
      decreased the proportion and number of SP thymocytes compared with OVA(323-339)
      stimulated FTOC without anti-CTLA-4 Ab treatment. In addition, anti-CTLA-4 Ab
      treatment inhibited OVA(323-339)-induced expression of the early activation
      marker, CD69, in DP thymocytes, but increased CD69 in SP thymocytes. Similarly,
      CTLA-4 blockage decreased phosphorylation of ERK in DP thymocytes by Ag-specific
      TCR engagement, but increased phosphorylation of ERK in SP thymocytes. CTLA-4
      blockage inhibited deletion of DP thymocytes treated with a high dose of OVA(323
      339), whereas CTLA-4 blockage did not inhibit deletion of DP thymocytes treated
      with a low dose of OVA(323-339). We conclude that CTLA-4 positively regulates the
      activation of DP thymocytes, resulting in their deletion, whereas blocking CTLA-4
      suppresses the activation of DP thymocytes, leading to inhibition of DP thymocyte
      deletion. In contrast, CTLA-4 negatively regulates the activation of SP
      thymocytes.

PMID- 15557156
TI  - Tolerance induction by veto CTLs in the TCR transgenic 2C mouse model. I.
      Relative reactivity of different veto cells.
AB  - Several bone marrow cells and lymphocyte subpopulations, known as veto cells,
      were shown to induce transplantation tolerance across major histocompatibility
      Ags. Due to the low frequency of the effector T cells against which the veto
      cells inhibitory activity is aimed, the fate of the effector cells was
      traditionally followed indirectly by functional limiting dilution assays, which
      are cumbersome and depend on numerous parameters. In the present study the fate
      of the effector T cells was monitored directly by FACS, using TCR transgenic
      mouse CD8(+) T cells in which the transgene is directed against H-2(d) (the 2C
      model). This assay is validated by demonstrating the potency, selectivity,
      radiation sensitivity, and contact dependency of anti-third-party CTLs previously
      demonstrated by the limiting dilution assay. In contrast to veto CTLs,
      nonactivated CD8(+) T cells lack veto activity. Comparison by FACS in the 2C
      model revealed a hierarchy of veto cells, in the order of veto CTLs activated NK
      cells, activated CD4(+) T cells, and activated B cells. The latter cells as well
      as nonactivated CD4(+) or NK cells were shown to be completely devoid of veto
      activity.

PMID- 15557157
TI  - Tolerance induction by veto CTLs in the TCR transgenic 2C mouse model. II.
      Deletion of effector cells by Fas-Fas ligand apoptosis.
AB  - The direct assay of veto CTLs in the 2C mouse model enables monitoring, by FACS,
      the fate of the TCR transgenic effector CD8(+) T cells, the transgene of which
      can be stained with clonotypic Ab 1B2. After the addition of veto cells,
      CD8(+)1B2(+) effector cells increasingly express annexin V, and maximal apoptosis
      is attained 72 h after initiation of MLR. This veto activity can be partially
      blocked by anti-CD8 Abs directed against the allele expressed by the veto CTLs,
      but not by the effector cells. When effector CD8(+) T cells were from 2C mice,
      which lack Fas expression ((2CX lpr)F(2)), deletion of effector cells was not
      exhibited by veto cells. The protein levels of the apoptosis inhibitors FLIP and
      Bcl2 in purified CD8(+)1B2(+) effector cells at different time points after MLR
      showed an initial up-regulation of these inhibitors, with marked reduction of
      FLIP, but not of Bcl2, by 48 h after initiation of culture. Taken together, these
      results are in accordance with a Fas-FasL-based mechanism in which prolonged
      binding between the effector cell and the veto cell might be required to allow
      FLIP to be down-regulated. Such prolonged interaction might be afforded through
      the interaction of CD8 molecules on the veto cell with the alpha3 domain of H2
      class 1 on the effector cell.

PMID- 15557158
TI  - IFN beta accelerates autoimmune type 1 diabetes in nonobese diabetic mice and
      breaks the tolerance to beta cells in nondiabetes-prone mice.
AB  - Genetic and environmental factors are decisive in the etiology of type 1
      diabetes. Viruses have been proposed as a triggering environmental event and some
      evidences have been reported: type I IFNs exist in the pancreata of diabetic
      patients and transgenic mice expressing these cytokines in beta cells develop
      diabetes. To determine the role of IFNbeta in diabetes, we studied transgenic
      mice expressing human IFNbeta in the beta cells. Autoimmune features were found:
      MHC class I islet hyperexpression, T and B cells infiltrating the islets and
      transfer of the disease by lymphocytes. Moreover, the expression of beta(2)
      microglobulin, preproinsulin, and glucagon in the thymus was not altered by
      IFNbeta, thus suggesting that the disease is caused by a local effect of IFNbeta,
      strong enough to break the peripheral tolerance to beta cells. This is the first
      report of the generation of NOD (a model of spontaneous autoimmune diabetes) and
      nonobese-resistant (its homologous resistant) transgenic mice expressing a type I
      IFN in the islets: transgenic NOD and nonobese-resistant mice developed
      accelerated autoimmune diabetes with a high incidence of the disease. These
      results indicate that the antiviral cytokine IFNbeta breaks peripheral tolerance
      to beta cells, influences the insulitis progression and contributes to
      autoimmunity in diabetes and nondiabetes- prone mice.

PMID- 15557159
TI  - Follicular dendritic cells produce IL-15 that enhances germinal center B cell
      proliferation in membrane-bound form.
AB  - Factors that control the survival and proliferation of Ag-stimulated B cells
      within the germinal center (GC) are crucial for humoral immune responses with
      high affinity Abs against infectious agents. The follicular dendritic cell (FDC)
      is known as a key cellular component of the GC microenvironment for GC-B cell
      survival and proliferation. In this study, we report that IL-15 is produced by
      human FDC in vivo and by an FDC cell line, FDC/HK cells, in vitro. IL-15 is
      captured by IL-15Ralpha on the surface of FDC/HK cells. The surface IL-15 is
      functionally active and augments GC-B cell proliferation. Because GC-B cells have
      the signal-transducing components (IL-2/15Rbetagamma), but not a receptor for
      binding of soluble IL-15 (IL-15Ralpha), IL-15 signaling is possibly transduced by
      transpresentation from FDCs to GC-B cells via cell-cell contact. Together, these
      results suggest that IL-15 from FDC, in membrane-bound form, plays an important
      role in supporting GC-B cell proliferation, proposing a new target for immune
      modulation as well as treatment of B cell tumors of GC origin.

PMID- 15557160
TI  - Impact of CCR7 on priming and distribution of antiviral effector and memory CTL.
AB  - The chemokine receptor CCR7 is a key factor in the coordinate migration of T
      cells and dendritic cells (DC) into and their localization within secondary
      lymphoid organs. In this study we investigated the impact of CCR7 on CD8(+) T
      cell responses by infecting CCR7(-/-) mice with lymphocytic choriomeningitis
      virus (LCMV). We found that the absence of CCR7 affects the magnitude of an
      antiviral CTL response during the acute phase, with reduced numbers of virus
      specific CTL in all lymphoid and nonlymphoid organs tested. On the single cell
      level, CCR7-deficient CTL gained full effector function, such that antiviral
      protection in CCR7-deficient mice was complete, but delayed. Similarly, adoptive
      transfer experiments using DC from CCR7-deficient or competent mice for the
      priming of CCR7-positive or CCR7-negative CD8(+) T cells, respectively, revealed
      that ectopic positioning of DC and CTL outside organized T cell zones results in
      reduced priming efficacy. In the memory phase, CCR7-deficient mice maintained a
      stable LCMV-specific CTL population, predominantly in nonlymphoid organs, and
      rapidly mounted protective CTL responses against a challenge infection with a
      vaccinia virus recombinant for the gp33 epitope of LCMV. Taken together, the CCR7
      dependent organization of the T cell zone does not appear to be a prerequisite
      for antiviral effector CTL differentiation and the sustenance of antiviral memory
      responses in lymphoid or peripheral tissues.

PMID- 15557161
TI  - Shortening the infectious period does not alter expansion of CD8 T cells but
      diminishes their capacity to differentiate into memory cells.
AB  - Following a primary immune response, a portion of effector T cells gives rise to
      long-lived memory cells. Although primary expansion and differentiation of
      effector CD8 T cells is dictated by a brief exposure to Ag, it is unclear whether
      full memory differentiation is also programmed within the same short window. By
      carefully modulating the kinetics of Listeria monocytogenes infection, we
      analyzed the requirements for the programming of effector and memory T cell
      development in vivo. We find that although limiting the infectious period to the
      first 24-48 h does not impact the size of the primary CD8 response, the ensuing
      memory population is significantly diminished. This effect is particularly
      pronounced in the development of tissue-homing memory cells and is inversely
      proportional to the initial infectious dose. In contrast to CD8 responses, the
      differentiation of primary CD4 responses was highly dependent on the continued
      presence of the infection. Shortening the duration of the infection greatly
      reduced the development of CD4 effector responses in the spleen and prevented
      their trafficking to peripheral sites of infection. We propose that the stimulus
      received by CD8 T cells during the early stages of infection largely contribute
      to the differentiation of CD8 effector cells, whereas continued or distinct
      signals received at later stages influence their ability to differentiate into
      memory cells.

PMID- 15557162
TI  - Molecular characterization of a novel immune receptor restricted to the monocytic
      lineage.
AB  - Homology basic local alignment search tool search was conducted using a sequence
      encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a
      previously described homologous sequence termed CMRF-35. On the basis of this
      information, we cloned a full length cDNA corresponding to a novel member of this
      family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene,
      located in chromosome 17q25.1, encodes for a protein of 205 aa that contains an
      extracellular region comprising an Ig-like domain and a transmembrane region with
      a positively charged amino acid residue (lysine), that predicted its putative
      association with an adapter molecule. Indeed, the interaction between IREM-2 and
      DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and
      using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be
      restricted to mature hemopoietic cells of the monocytic and myeloid dendritic
      cell lineages. In vitro differentiation to macrophages or immature dendritic
      cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs,
      IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced
      NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced
      TNF-alpha production. Taken together, our results indicate that IREM-2 is a novel
      activating receptor of the Ig-superfamily in the monocytic lineage.

PMID- 15557163
TI  - IL-19 induced Th2 cytokines and was up-regulated in asthma patients.
AB  - IL-19 belongs to the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22,
      melanoma differentiation-associated gene-7 (IL-24), and AK155 (IL-26). IL-10 has
      been shown to inhibit allergen-induced airway hyperreactivity and inflammation.
      To determine whether IL-19 was also associated with asthma, we used ELISA to
      analyze the serum level of IL-19 in patients with asthma and found that their
      serum IL-19 levels were twice those of healthy controls. Patients with a high
      level of IL-19 also had high levels of IL-4 and IL-13. In a dust mite-induced
      murine model of asthma, we found that IL-19 level in asthmatic BALB/cJ mice was
      also twice that of healthy control mice. IL-19 transcript was also induced in the
      lungs of asthmatic mice. Electroporation i.m. of the IL-19 gene into healthy mice
      up-regulated IL-4 and IL-5, but not IL-13. However, IL-19 up-regulated IL-13 in
      asthmatic mice. In vitro, IL-19 induced IL-4, IL-5, IL-10, and IL-13 production
      by activated T cells. Activation of T cells was required for induction of IL-13
      because IL-19 did not induce IL-13 production on nonstimulated T cells. Taken
      together, these results demonstrated that IL-19 up-regulates Th2 cytokines on
      activated T cells and might play an important role in the pathogenesis of asthma.

PMID- 15557164
TI  - Phenotypic and functional characterization of CD4 T cells expressing killer Ig
      like receptors.
AB  - Killer Ig-like receptors (KIR) are commonly found on human NK cells, gammadelta T
      cells, and CD8 T cells. Although KIR(+) CD4 T cells are found in certain
      patients, their prevalence in healthy donors is controversial. We now provide
      definitive proof that such cells are present in most individuals, and report on
      their frequency, surface phenotype, cytokine profile, and Ag specificity. The
      number of KIR(+) CD4 T cells detected in peripheral blood increased with age. In
      contrast with regular KIR(-) CD4 T cells, the majority of KIR(+) CD4 T cells
      lacked surface expression of CD27, CD28, CCR4, and CCR7, but did express CD57 and
      2B4. In addition, KIR were detected on approximately one-tenth of CD28(-) and
      CD57(+) memory CD4 T cells. In line with the absence of the Th2 marker CCR4, the
      KIR(+) CD4 cells produced mainly IFN-gamma and little IL-4, IL-10, or IL-17 upon
      TCR triggering. Furthermore, the KIR(+) population contained cells that responded
      to recall Ags in an HLA class II-restricted fashion. Together, our data indicate
      that KIR-expressing CD4 T cells are predominantly HLA class II-restricted
      effector memory Th1 cells, and that a significant, previously unrecognized
      fraction of effector memory Th1 cells expresses KIR.

PMID- 15557165
TI  - Individual nonobese diabetic mice exhibit unique patterns of CD8+ T cell
      reactivity to three islet antigens, including the newly identified widely
      expressed dystrophia myotonica kinase.
AB  - Spontaneous autoimmune diabetes development in NOD mice requires both CD8(+) and
      CD4(+) T cells. Three pathogenic CD8(+) T cell populations (represented by the
      G9C8, 8.3, and AI4 clones) have been described. Although the Ags for G9C8 and 8.3
      are known to be insulin and islet-specific glucose-6-phosphatase catalytic
      subunit-related protein, respectively, only mimotope peptides had previously been
      identified for AI4. In this study, we used peptide/MHC tetramers to detect and
      quantify these three pathogenic populations among beta cell-reactive T cells
      cultured from islets of individual NOD mice. Even within age-matched groups, each
      individual mouse exhibited a unique distribution of beta cell-reactive CD8(+) T
      cells, both in terms of the number of tetramer-staining populations and the
      relative proportion of each population in the islet infiltrate. Thus, the
      inflammatory process in each individual follows its own distinctive course.
      Screening of a combinatorial peptide library in positional scanning format led to
      the identification of a peptide derived from dystrophia myotonica kinase (DMK)
      that is recognized by AI4-like T cells. Importantly, the antigenic peptide is
      naturally processed and presented by DMK-transfected cells. DMK is a widely
      expressed protein that is nonetheless the target of a beta cell-specific
      autoimmune response.

PMID- 15557166
TI  - Mechanisms for macrophage-mediated HIV-1 induction.
AB  - Viral latency is a long-term pathogenic condition in patients infected with HIV
      1. Low but sustained virus replication in chronically infected cells can be
      activated by stimulation with proinflammatory cytokines such as TNF-alpha, IL-1
      beta, or other host factors. However, the precise mechanism by which cellular
      activation induces latently infected cells to produce virions has remained
      unclear. In the present report, we present evidence that activation of HIV-1
      replication in latently infected U1 or ACH2 cells by human macrophages is
      mediated by a rapid nuclear localization of NF-kappaB p50/p65 dimer with
      concomitant increased expression of proinflammatory cytokines. Multiplexed RT-PCR
      amplification of mRNA isolated from cocultures of macrophages and U1 and ACH2
      cells showed significant induction of IL-1beta, IL-6, IL-8, TNF-alpha, and TGF
      beta expression within 3 h of coincubation. Fixation of macrophages, U-1, or ACH2
      cells with paraformaldehyde before coculture completely abrogated the induction
      of NF-kappaB subunits and HIV-1 replication, suggesting that cooperative
      interaction between the two cell types is an essential process for cellular
      activation. Pretreatment of macrophage-U1 or macrophage-ACH2 cocultures with
      neutralizing anti-TNF-alpha Ab down-regulated the replication of HIV-1. In
      addition, pretreatment of macrophage-U1 or macrophage-ACH2 cocultures with the NF
      kappaB inhibitor (E)3-[(4-methylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7082)
      prevented the induction of cytokine expression, indicating a pivotal role of NF
      kappaB-mediated signaling in the reactivation of HIV-1 in latently infected cells
      by macrophages. These results provide a mechanism by which macrophages induce HIV
      1 replication in latently infected cells.

PMID- 15557167
TI  - Antiapoptotic microenvironment of acute myeloid leukemia.
AB  - We showed previously that tumor-derived supernatant (TSN) from acute myeloid
      leukemia (AML) myeloblasts inhibits peripheral blood T cell activation and
      proliferation, rendering the T cells functionally incompetent. We show here that
      the AML TSN also significantly delays apoptosis of both resting and stimulated T
      cells, as judged by reduction in annexin V/propidium iodide staining. In
      addition, we show that this is not unique to T cells and that AML TSN inhibits
      apoptosis of peripheral B cells, neutrophils, and monocytes. Furthermore, it also
      enhances the survival of other AML myeloblasts with lower viability.
      Investigations into the mechanism demonstrate a reduction in the cleavage of
      procaspase-3, -8, and -9 and the caspase substrate, poly(ADP-ribose)polymerase
      (PARP). This may be due to Bcl-2, which is normally down-regulated in CD3/CD28
      stimulated T cells, but is maintained in the presence of AML TSN. We conclude
      that AML cells generate an antiapoptotic microenvironment that favors the
      survival of malignant cells, but also inhibits apoptosis of other normal
      hemopoietic cells. Reversal of these immunosuppressive effects and restoration of
      normal immune responses in patients with AML would improve the success of
      immunotherapy protocols.

PMID- 15557168
TI  - Activation of dendritic cells that cross-present tumor-derived antigen licenses
      CD8+ CTL to cause tumor eradication.
AB  - The fate of naive CD8(+) T cells is determined by the environment in which they
      encounter MHC class I presented peptide Ags. The manner in which tumor Ags are
      presented is a longstanding matter of debate. Ag presentation might be mediated
      by tumor cells in tumor draining lymph nodes or via cross-presentation by
      professional APC. Either pathway is insufficient to elicit protective antitumor
      immunity. We now demonstrate using a syngeneic mouse tumor model, expressing an
      Ag derived from the early region 1A of human adenovirus type 5, that the
      inadequate nature of the antitumor CTL response is not due to direct Ag
      presentation by the tumor cells, but results from presentation of tumor-derived
      Ag by nonactivated CD11c(+) APC. Although this event results in division of naive
      CTL in tumor draining lymph nodes, it does not establish a productive immune
      response. Treatment of tumor-bearing mice with dendritic cell-stimulating
      agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector
      function capable to eradicate established tumors. For efficacy of anti-CD40
      treatment, CD40 ligation of host APC is required because adoptive transfer of
      CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor
      bearing mice did not lead to productive antitumor immunity after CD40 triggering
      in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb
      with respect to CD8(+) CTL efflux and tumor eradication. Together these results
      indicate that dendritic cells, depending on their activation state, orchestrate
      the outcome of CTL-mediated immunity against tumors, leading either to an
      ineffective immune response or potent antitumor immunity.

PMID- 15557169
TI  - Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in
      human endometrium by estradiol and progesterone.
AB  - Uterine NK (uNK) cells express a unique set of markers compared with blood NK
      cells. However, recent studies suggest that uNK cells may be derived from the
      recruitment of blood NK cells into the endometrium. In this study, we used an in
      vitro organ culture system to demonstrate that estradiol induces expression of
      chemokines CXCL10 and/or CXCL11 within human endometrium in 85% of patient
      samples tested. The average increase in gene expression after 10(-9) M estradiol
      treatment was 8.5-fold for CXCL10 and 7.7-fold for CXCL11 compared with medium
      alone. We observed that a specific estrogen receptor antagonist (ICI182780) was
      able to prevent chemokine gene induction, indicating that the effect of estradiol
      was receptor mediated. Moreover, our study showed that progesterone induced
      CXCL10 and CXCL11 expression in 83% of endometrial samples tested. We have also
      found that uNK cells and blood NK cells express the receptor for CXCL10 and
      CXCL11, CXCR3, with the highest expression found on uNK cells and CD56(bright)
      blood NK cells. These data indicate that sex hormones induce specific chemokines
      in nonpregnant human endometrium that can activate NK cell migration, and suggest
      that this mechanism may account for the increased NK cell numbers in endometrium
      during the menstrual cycle.

PMID- 15557170
TI  - Characterization of tumor reactivity of human V gamma 9V delta 2 gamma delta T
      cells in vitro and in SCID mice in vivo.
AB  - Human Vgamma9Vdelta2 gammadelta T cells are selectively activated by bacterial
      phosphoantigens and aminobisphosphonates and exert potent cytotoxicity toward
      various tumor cells. In this study we have characterized the cytotoxic reactivity
      of gammadelta T cell lines established from healthy donors by stimulation with
      aminobisphosphonate alendronate toward melanoma MeWo and pancreatic
      adenocarcinomas Colo357 and PancTu1 lines in vitro and in vivo upon adoptive
      transfer into SCID mice. Lysis of all tumor cells was enhanced when gammadelta
      effector cells were preactivated with phosphoantigens. Recognition of MeWo was
      TCR dependent, as shown by anti-TCR Ab blockade, whereas only the phosphoantigen
      mediated increased, but not the basal, lysis of Colo357 and PancTu1 was inhibited
      by anti-TCR Ab. Furthermore, lysis of Colo357, but not that of MeWo or PancTu1,
      was completely inhibited by the pan-caspase inhibitor zVAD, indicating different
      recognition and effector mechanisms involved in the gammadelta T cell/tumor cell
      interactions. Upon transfer into SCID mice, alendronate-activated gammadelta T
      cells given together with IL-2 and alendronate significantly prolonged the
      survival of SCID mice inoculated with human tumor cells. The best results were
      thus obtained when gammadelta T cells were repetitively given five times over a
      period of 30 days. With this protocol, human gammadelta T cells prolonged the
      mean survival of mice inoculated with MeWo melanoma from 28.5 to 87.3 days (p <
      0.0001) and in the case of PancTu1 adenocarcinoma from 23.0 to 48.4 days (p <
      0.0001). We conclude that an effective gammadelta T cell-based immunotherapy
      might require activation of endogenous gammadelta T cells with
      aminobisphosphonate (or phosphoantigen) and IL-2, followed by adoptive transfer
      of in vitro expanded gammadelta T cells.

PMID- 15557171
TI  - Presence of diabetes-inhibiting, glutamic acid decarboxylase-specific, IL-10
      dependent, regulatory T cells in naive nonobese diabetic mice.
AB  - Immunization of NOD mice with autoantigens such as glutamic acid decarboxylase
      (GAD) 221-235 peptide (p221) can induce Ag-specific CD4(+) T regulatory (Tr)
      cells. However, it is unclear whether these Tr cells acquire their regulatory
      capacity due to immunization or whether they are constitutively harbored in
      unimmunized naive mice. To address this question, we used an I-Ag7 tetramer to
      isolate p221-specific T cells from naive NOD mice (N221(+) cells) after peptide
      specific in vitro expansion. The N221(+) T cells produced IFN-gamma and IL-10,
      but very little IL-4, in response to p221 stimulation. These T cells could
      function as regulatory cells and inhibit in vitro proliferation of diabetogenic
      BDC2.5 cells. This suppressive activity was cell contact-independent and was
      abrogated by Abs to IL-10 or IL-10R. Interestingly, IL-2 produced by other T
      cells present in the cell culture induced unactivated N221(+) T cells to exhibit
      regulatory activities involving production of IL-10. In vivo, N221(+) cells
      inhibited diabetes development when cotransferred with NOD splenocytes into
      NOD/scid recipients. Together, these results demonstrate that p221-specific IL-10
      dependent Tr cells, including Tr type 1 cells, are present in naive NOD mice. The
      use of spontaneously arising populations of GAD peptide-specific Tr cells may
      represent a promising immunotherapeutic approach for preventing type 1 diabetes.

PMID- 15557172
TI  - Molecular mechanisms of CD200 inhibition of mast cell activation.
AB  - CD200 and its receptor CD200R are both type I membrane glycoproteins that contain
      two Ig-like domains. Engagement of CD200R by CD200 inhibits activation of myeloid
      cells. Unlike the majority of immune inhibitory receptors, CD200R lacks an ITIM
      in the cytoplasmic domain. The molecular mechanism of CD200R inhibition of
      myeloid cell activation is unknown. In this study, we examined the CD200R
      signaling pathways that control degranulation of mouse bone marrow-derived mast
      cells. We found that upon ligand binding, CD200R is phosphorylated on tyrosine
      and subsequently binds to adapter proteins Dok1 and Dok2. Upon phosphorylation,
      Dok1 binds to SHIP and both Dok1 and Dok2 recruit RasGAP, which mediates the
      inhibition of the Ras/MAPK pathways. Activation of ERK, JNK, and p38 MAPK are all
      inhibited by CD200R engagement. The reduced activation of these MAPKs is
      responsible for the observed inhibition of mast cell degranulation and cytokine
      production. Similar signaling events were also observed upon CD200R engagement in
      mouse peritoneal cells. These data define a novel inhibitory pathway used by
      CD200R in modulating mast cell function and help to explain how engagement of
      this receptor in vivo regulates myeloid cell function.

PMID- 15557173
TI  - Antibody repertoire development in fetal and neonatal pigs. VII. Characterization
      of the preimmune kappa light chain repertoire.
AB  - Combinatorial diversity is highly restricted in the preimmune porcine H chain
      repertoire compared with that in humans and mice. This raised the question of
      whether similar restriction characterized the preimmune L chain repertoire. In
      this study we present evidence that >90% of all expressed Vkappa genes in the
      porcine preimmune repertoire belong to three subfamilies of Vkappa genes that
      share 87% sequence similarity with human IGKV2. This porcine Vkappa family also
      shares sequence similarity with some, but not all, Vkappa genes from sheep.
      Hybridization with sperm DNA and sequence analyses of polynucleotides from
      overlapping bacterial artificial chromosome clones suggest swine possess
      approximately 60 IGVK2 genes. The latter method also revealed that certain IGKV2
      subfamilies are not expressed in the preimmune repertoire. Six members of an
      IGVK1 family were also expressed as part of the preimmune repertoire, and these
      shared 87% sequence similarity with human IGVK1. Five Jkappa segments, complete
      with recombination signal sequences and separated by approximately 300 nt, were
      identified approximately 3 kb upstream of a single Ckappa. Surprisingly, Jkappa2
      accounted for >90% of all framework region 4 sequences in the preimmune
      repertoire. These findings show that swine use approximately 10 IGVK2 genes from
      three of six subfamilies and preferentially one Jkappa segment to generate their
      preimmune kappa repertoire. These studies, like those of porcine Ig constant
      regions and MHC genes, also indicate unexpected high sequence similarity with
      their human counterparts despite differences in phylogeny and the mechanism of
      repertoire diversification.

PMID- 15557174
TI  - Biochemical analysis of the regulatory T cell protein lymphocyte activation gene
      3 (LAG-3; CD223).
AB  - Lymphocyte activation gene-3 (LAG-3; CD223) is a CD4-related transmembrane
      protein that binds to MHC class II molecules. We have recently shown that LAG-3
      is required for maximal regulatory T cell function, and that ectopic expression
      of LAG-3 is sufficient to confer regulatory activity. In this study we show that
      LAG-3 is cleaved within the D4 transmembrane domain connecting peptide into two
      fragments that remain membrane associated: a 54-kDa fragment that contains all
      the extracellular domains and oligomerizes with full-length LAG-3 (70 kDa) on the
      cell surface via the D1 domain, and a 16-kDa peptide that contains the
      transmembrane and cytoplasmic domains. This NH(2)-terminal fragment is
      subsequently released as soluble LAG-3 (sLAG-3), a process that is increased
      after T cell activation in vitro and in vivo, and is found in the sera of C57BL/6
      and RAG-1(-/-) mice. Modulation of LAG-3 cleavage may contribute to the function
      of this key regulatory T cell protein.

PMID- 15557175
TI  - Transporter associated with antigen processing preselection of peptides binding
      to the MHC: a bioinformatic evaluation.
AB  - TAP is responsible for the transit of peptides from the cytosol to the lumen of
      the endoplasmic reticulum. In an immunological context, this event is followed by
      the binding of peptides to MHC molecules before export to the cell surface and
      recognition by T cells. Because TAP transport precedes MHC binding, TAP
      preferences may make a significant contribution to epitope selection. To assess
      the impact of this preselection, we have developed a scoring function for TAP
      affinity prediction using the additive method, have used it to analyze and extend
      the TAP binding motif, and have evaluated how well this model acts as a
      preselection step in predicting MHC binding peptides. To distinguish between MHC
      alleles that are exclusively dependent on TAP and those exhibiting only a partial
      dependence on TAP, two sets of MHC binding peptides were examined: HLA-A*0201 was
      selected as a representative of partially TAP-dependent HLA alleles, and HLA
      A*0301 represented fully TAP-dependent HLA alleles. TAP preselection has a
      greater impact on TAP-dependent alleles than on TAP-independent alleles. The
      reduction in the number of nonbinders varied from 10% (TAP-independent) to 33%
      (TAP-dependent), suggesting that TAP preselection is an important component in
      the successful in silico prediction of T cell epitopes.

PMID- 15557176
TI  - SHIP2 is recruited to the cell membrane upon macrophage colony-stimulating factor
      (M-CSF) stimulation and regulates M-CSF-induced signaling.
AB  - The Src homology 2-containing inositol phosphatase SHIP1 functions in hemopoietic
      cells to limit activation events mediated by PI3K products, including Akt
      activation and cell survival. In contrast to the limited cellular expression of
      SHIP1, the related isoform SHIP2, is widely expressed in both parenchymal and
      hemopoietic cells. The goal of this study was to determine how SHIP2 functions to
      regulate M-CSF signaling. We report that 1) SHIP2 was tyrosine-phosphorylated in
      M-CSF-stimulated human alveolar macrophages, human THP-1 cells, murine
      macrophages, and the murine macrophage cell line RAW264; 2) SHIP2 associated with
      the M-CSF receptor after M-CSF stimulation; and 3) SHIP2 associated with the
      actin-binding protein filamin and localization to the cell membrane, requiring
      the proline-rich domain, but not on the Src homology 2 domain of SHIP2. Analyzing
      the function of SHIP2 in M-CSF-stimulated cells by expressing either wild-type
      SHIP2 or an Src homology 2 domain mutant of SHIP2 reduced Akt activation in
      response to M-CSF stimulation. In contrast, the expression of a catalytically
      deficient mutant of SHIP2 or the proline-rich domain of SHIP2 enhanced Akt
      activation. Similarly, the expression of wild-type SHIP2 inhibited NF-kappaB
      mediated gene transcription. Finally, fetal liver-derived macrophages from SHIP2
      gene knockout mice enhanced activation of Akt in response to M-CSF treatment.
      These data suggest a novel regulatory role for SHIP2 in M-CSF-stimulated myeloid
      cells.

PMID- 15557177
TI  - The glycosylation of human serum IgD and IgE and the accessibility of identified
      oligomannose structures for interaction with mannan-binding lectin.
AB  - Analysis of the glycosylation of human serum IgD and IgE indicated that
      oligomannose structures are present on both Igs. The relative proportion of the
      oligomannose glycans is consistent with the occupation of one N-linked site on
      each heavy chain. We evaluated the accessibility of the oligomannose glycans on
      serum IgD and IgE to mannan-binding lectin (MBL). MBL is a member of the
      collectin family of proteins, which binds to oligomannose sugars. It has already
      been established that MBL binds to other members of the Ig family, such as
      agalactosylated glycoforms of IgG and polymeric IgA. Despite the presence of
      potential ligands, MBL does not bind to immobilized IgD and IgE. Molecular
      modeling of glycosylated human IgD Fc suggests that the oligomannose glycans
      located at Asn(354) are inaccessible because the complex glycans at Asn(445)
      block access to the site. On IgE, the additional C(H)2 hinge domain blocks access
      to the oligomannose glycans at Asn(394) on one H chain by adopting an
      asymmetrically bent conformation. IgE contains 8.3% Man(5)GlcNAc(2) glycans,
      which are the trimmed products of the Glc(3)Man(9)GlcNAc(2) oligomannose
      precursor. The presence of these structures suggests that the C(H)2 domain flips
      between two bent quaternary conformations so that the oligomannose glycans on
      each chain become accessible for limited trimming to Man(5)GlcNAc(2) during
      glycan biosynthesis. This is the first study of the glycosylation of human serum
      IgD and IgE from nonmyeloma proteins.

PMID- 15557178
TI  - The membrane-proximal immunoreceptor tyrosine-based inhibitory motif is critical
      for the inhibitory signaling mediated by Siglecs-7 and -9, CD33-related Siglecs
      expressed on human monocytes and NK cells.
AB  - Siglec-7 and Siglec-9 are two members of the recently characterized CD33-related
      Siglec family of sialic acid binding proteins and are both expressed on human
      monocytes and NK cells. In addition to their ability to recognize sialic acid
      residues, these Siglecs display two conserved tyrosine-based motifs in their
      cytoplasmic region similar to those found in inhibitory receptors of the immune
      system. In the present study, we use the rat basophilic leukemia (RBL) model to
      examine the potential of Siglecs-7 and -9 to function as inhibitory receptors and
      investigate the molecular basis for this. We first demonstrate that Siglecs-7 and
      -9 are able to inhibit the FcepsilonRI-mediated serotonin release from RBL cells
      following co-crosslinking. In addition, we show that under these conditions or
      after pervanadate treatment, Siglecs-7 and -9 associate with the Src homology
      region 2 domain-containing phosphatases (SHP), SHP-1 and SHP-2, both in
      immunoprecipitation and in fluorescence microscopy experiments using GFP fusion
      proteins. We then show by site-directed mutagenesis that the membrane-proximal
      tyrosine motif is essential for the inhibitory function of both Siglec-7 and -9,
      and is also required for tyrosine phosphorylation and recruitment of SHP-1 and
      SHP-2 phosphatases. Finally, mutation of the membrane-proximal motif increased
      the sialic acid binding activity of Siglecs-7 and -9, raising the possibility
      that "inside-out" signaling may occur to regulate ligand binding.

PMID- 15557179
TI  - A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates.
AB  - The development of a safe and effective mucosal adjuvant is a crucial step toward
      a mucosal HIV/AIDS vaccine. This study seeks to determine the promise of a
      nontoxic mutant of cholera toxin (mCT; E112K) as a mucosal adjuvant in nonhuman
      primates. HIV-1 gp120 was nasally administered together with mCT E112K or native
      CT (nCT) as adjuvant on five to six occasions over a 6- to 8-wk period to groups
      of four rhesus macaques and alone to two monkeys that acted as controls. Macaques
      given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG
      and IgA Ab responses with virus-neutralizing activity in both their plasma and
      mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab
      forming cells in their mucosal and peripheral lymphoid tissues and of IL-4
      producing Th2-type CD4-positive (CD4(+)) T cells than did controls. Even though
      significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal
      damage was observed only in the nCT-treated, but not in the control or mCT E112K
      treated groups. These results clearly show that mCT E112K is an effective and
      safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.

PMID- 15557180
TI  - Gene expression profiling of host response in models of acute HIV infection.
AB  - HIV infection is characterized by a host response composed of adaptive and innate
      immunity that partially limits viral replication; however, it ultimately fails in
      eradicating the virus. To model host gene expression during acute HIV infection,
      we infected cynomolgus macaques with the SIV/HIV-1 chimeric virus, SHIV89.6P, and
      profiled gene expression in peripheral blood over a 5-wk period using a high
      density cDNA microarray. We demonstrate that viral challenge induced a widespread
      suppression of genes regulating innate immunity, including the LPS receptors,
      CD14 and TLR4. An overexpression of 16 IFN-stimulated genes was also observed in
      response to infection; however, it did not correlate with control over viral
      titers. A statistical analysis of the dataset identified 10 genes regulating
      apoptosis with differential expression during the first 2 wk of infection (p <
      0.004). Quantitative real-time PCR verified transcriptional increases in IFN
      alpha-inducible genes and decreases in genes regulating innate immunity.
      Therefore, the persistence of high viral loads despite an extensive IFN response
      suggests that HIV can resist in vivo IFN treatment despite published reports of
      in vitro efficacy. The transcriptional suppression of genes regulating innate
      immunity may allow HIV to evade acute host responses and establish a chronic
      infection and may reduce innate host defense against opportunistic infections.

PMID- 15557181
TI  - RON receptor tyrosine kinase, a negative regulator of inflammation, inhibits HIV
      1 transcription in monocytes/macrophages and is decreased in brain tissue from
      patients with AIDS.
AB  - Activation of macrophages and microglia cells after HIV-1 infection and their
      production of inflammatory mediators contribute to HIV-associated CNS diseases.
      The mechanisms that initiate and maintain inflammation after HIV-1 infection in
      the brain have not been well studied. Furthermore, it is not understood why in
      HIV-associated CNS disease, macrophages and microglia are biased toward
      inflammation rather than production of mediators that control inflammation. We
      have focused on the receptor tyrosine kinase RON, a critical negative regulator
      of macrophage function and inflammation, to determine whether this receptor
      regulates HIV-1 expression. Overexpressing RON in monocytes/macrophages
      demonstrates that RON inhibits HIV-1 proviral transcription in part by decreasing
      the binding activity of NF-kappaB to the HIV-1 long terminal repeat. Because
      macrophages and microglia cells are a critical reservoir for HIV-1 in the CNS, we
      examined brain tissues for RON expression and detected RON in astrocytes,
      cortical neurons, and monocytoid cells. RON was detected in all control patients
      who were HIV seronegative (n = 7), whereas six of nine brain samples obtained
      from AIDS patients exhibited reduced RON protein. These data suggest that RON
      initiates signaling pathways that negatively regulate HIV-1 transcription in
      monocytes/macrophages and that HIV-1 suppresses RON function by decreasing
      protein levels in the brain to assure efficient replication. Furthermore, HIV-1
      infection would compromise the ability of RON to protect against inflammation and
      consequent CNS damage.

PMID- 15557182
TI  - Activation of virus-specific CD8+ T cells by lipopolysaccharide-induced IL-12 and
      IL-18.
AB  - Virus-specific T cells represent a hallmark of Ag-specific, adaptive immunity.
      However, some T cells also demonstrate innate functions, including non-Ag
      specific IFN-gamma production in response to microbial products such as LPS or
      exposure to IL-12 and/or IL-18. In these studies we examined LPS-induced cytokine
      responses of CD8(+) T cells directly ex vivo. Following acute viral infection, 70
      80% of virus-specific T cells will produce IFN-gamma after exposure to LPS
      induced cytokines, and neutralization experiments indicate that this is mediated
      almost entirely through production of IL-12 and IL-18. Different combinations of
      these cytokines revealed that IL-12 decreases the threshold of T cell activation
      by IL-18, presenting a new perspective on IL-12/IL-18 synergy. Moreover, memory T
      cells demonstrate high IL-18R expression and respond effectively to the
      combination of IL-12 and IL-18, but cannot respond to IL-18 alone, even at high
      cytokine concentrations. This demonstrates that the synergy between IL-12 and IL
      18 in triggering IFN-gamma production by memory T cells is not simply due to up
      regulation of the surface receptor for IL-18, as shown previously with naive T
      cells. Together, these studies indicate how virus-specific T cells are able to
      bridge the gap between innate and adaptive immunity during unrelated microbial
      infections, while attempting to protect the host from cytokine-induced
      immunopathology and endotoxic shock.

PMID- 15557183
TI  - TLR-independent induction of dendritic cell maturation and adaptive immunity by
      negative-strand RNA viruses.
AB  - TLR signaling leads to dendritic cell (DC) maturation and immunity to diverse
      pathogens. The stimulation of TLRs by conserved viral structures is the only
      described mechanism leading to DC maturation after a virus infection. In this
      report, we demonstrate that mouse myeloid DCs mature normally after in vivo and
      in vitro infection with Sendai virus (SeV) in the absence of TLR3, 7, 8, or 9
      signaling. DC maturation by SeV requires virus replication not necessary for TLR
      mediated triggering. Moreover, DCs deficient in TLR signaling efficiently prime
      for Th1 immunity after infection with influenza or SeV, generating IFN-gamma
      producing T cells, CTLs and antiviral Abs. We have previously demonstrated that
      SeV induces DC maturation independently of the presence of type I IFN, which has
      been reported to mature DCs in a TLR-independent manner. The data presented here
      provide evidence for the existence of a novel intracellular pathway independent
      of TLR-mediated signaling responsible for live virus triggering of DC maturation
      and demonstrate its critical role in the onset of antiviral immunity. The
      revelation of this pathway should stimulate invigorating research into the
      mechanism for virus-induced DC maturation and immunity.

PMID- 15557184
TI  - Viral activation of macrophages through TLR-dependent and -independent pathways.
AB  - Induction of cytokine production is important for activation of an efficient host
      defense response. Macrophages constitute an important source of cytokines. In
      this study we have investigated the virus-cell interactions triggering induction
      of cytokine expression in macrophages during viral infections. We found that
      viral entry and viral gene products produced inside the cell are responsible for
      activation of induction pathways leading to IFN-alphabeta expression, indicating
      that virus-cell interactions on the cell surface are not enough. Moreover, by the
      use of cell lines expressing dominant negative versions of TLR-associated adaptor
      proteins we demonstrate that Toll/IL-1 receptor domain-containing adaptor
      inducing IFN-beta is dispensable for all virus-induced cytokine expression
      examined. However, a cell line expressing dominant negative MyD88 revealed the
      existence of distinct induction pathways because virus-induced expression of
      RANTES and TNF-alpha was totally blocked in this cell line whereas IFN-alphabeta
      expression was much less affected in the absence of signaling via MyD88. In
      support of this, we also found that inhibitory CpG motifs, which block TLR9
      signaling inhibited early HSV-2-induced TNF-alpha and RANTES expression
      dramatically whereas IFN-alphabeta induction was only slightly affected. This
      suggests that virus activates macrophages through distinct pathways, of which
      some are dependent on TLRs signaling through MyD88, whereas others seem to be
      independent of TLR signaling. Finally we demonstrate that IFN-alphabeta induction
      in HSV-2-infected macrophages requires a functional dsRNA-activated protein
      kinase molecule because cells expressing a dsRNA-dependent protein kinase version
      unable to bind dsRNA do not express IFN-alphabeta on infection.

PMID- 15557185
TI  - Interaction between complement regulators and Streptococcus pyogenes: binding of
      C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves
      two different cell surface molecules.
AB  - Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent
      causes of pharyngitis and skin infections in humans. Many virulence mechanisms
      have been suggested to be involved in the infectious process. Among them is the
      binding to the bacterial cell surface of the complement regulatory proteins
      factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein. Previous
      studies indicate that binding of these three regulators to the streptococcal cell
      involves the M protein encoded by the emm gene. M-type 18 strains are prevalent
      among clinical isolates and have been shown to interact with all three complement
      regulators simultaneously. Using isogenic strains lacking expression of the Emm18
      or the Enn18 proteins, we demonstrate in this study that, in contradistinction to
      previously described S. pyogenes strains, M18 strains bind the complement
      regulators factor H, FHL-1, and C4b-binding protein through two distinct cell
      surface proteins. Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds
      to the Enn18 protein. We propose that expression of two distinct surface
      structures that bind complement regulatory proteins represents a unique
      adaptation of M18 strains that enhances their resistance to opsonization by human
      plasma and increases survival of this particular S. pyogenes strain in the human
      host. These new findings illustrate that S. pyogenes has evolved diverse
      mechanisms for recruitment of complement regulatory proteins to the bacterial
      surface to evade immune clearance in the human host.

PMID- 15557186
TI  - Human CD8+ T cells recognize the 60-kDa cysteine-rich outer membrane protein from
      Chlamydia trachomatis.
AB  - The intracellular bacterial pathogen Chlamydia is sequestered from the host cell
      cytoplasm by remaining within an inclusion body during its replication cycle.
      Nevertheless, CD8(+) T cells recognizing Chlamydia Ags in the context of MHC
      class I molecules are primed during infection. We have recently described
      derivation of Chlamydia-specific human CD8(+) T cells by using infected dendritic
      cells as a surrogate system to reflect Chlamydia-specific CD8(+) T cell responses
      in vivo. These CD8(+) T cell clones recognize chlamydial Ags processed via the
      conventional class Ia processing pathway, as assessed by treatment of infected
      APC with lactacystin and brefeldin A, suggesting that the Ags are translocated
      from the chlamydial inclusion into the host cell cytosol. In this study, outer
      membrane protein 2 (OmcB) was identified as the Ag recognized by one of these
      Chlamydia-specific human CD8(+) T cells, and we defined the HLA*A0101-restricted
      epitope from this Ag. CD8(+) T cell responses to this epitope were present at
      high frequencies in the peripheral blood of both of two HLA*A0101 donors tested.
      In vitro chlamydial growth was completely inhibited by the OmcB-specific CD8(+) T
      cell clone independently of lytic mechanisms. OmcB is a 60-kDa protein that has
      been postulated to be associated with the Chlamydia outer membrane complex. The
      subcellular localization of OmcB to the cytosol of infected cells, as determined
      by conventional MHC class I Ag processing and presentation, suggests the
      possibility of an additional, cytosolic-associated function for this protein.

PMID- 15557187
TI  - Nitric oxide inhibits IgE-dependent cytokine production and Fos and Jun
      activation in mast cells.
AB  - NO is a cell-derived radical reported to inhibit mast cell degranulation and
      subsequent allergic inflammation, although whether its action is nonspecific or
      occurs via specific molecular mechanisms remains unknown. To examine this
      question, we set out to determine whether NO inhibits mast cell cytokine
      production, and, if so, whether it also alters FcepsilonRI-dependent signal
      transduction. As hypothesized, the radical inhibited IgE/Ag-induced IL-4, IL-6,
      and TNF production. Although NO did not influence phosphorylated JNK, p38 MAPK,
      or p44/42 MAPK, it did inhibit phosphorylation of phospholipase Cgamma1 and the
      AP-1 transcription factor protein c-Jun, but not NF-kappaB or CREB. NO further
      completely abrogated IgE/Ag-induced DNA-binding activity of the nuclear AP-1
      proteins Fos and Jun. These results show that NO is capable of inhibiting
      FcepsilonRI-dependent mast cell cytokine production at the level of gene
      regulation, and suggest too that NO may contribute to resolution of allergic
      inflammation.

PMID- 15557188
TI  - Platelet-activating factor and kinin-dependent vascular leakage as a novel
      functional activity of the soluble terminal complement complex.
AB  - The infrequent occurrence of septic shock in patients with inherited deficiencies
      of the terminal complement components experiencing meningococcal disease led us
      to suspect that the terminal complement complex is involved in vascular leakage.
      To this end, the permeabilizing effect of the cytolytically inactive soluble
      terminal complement complex (SC5b-9) was tested in a Transwell system measuring
      the amount of fluorescein-labeled BSA (FITC-BSA) leaked through a monolayer of
      endothelial cells. The complex caused increased permeability to FITC-BSA after 15
      min as opposed to the prompt response to bradykinin (BK). The effect of SC5b-9
      was partially reduced by HOE-140 or CV-3988, two selective antagonists of BK B2
      and platelet-activating factor receptors, respectively, and was completely
      neutralized by the mixture of the two antagonists. Also, DX-88, a specific
      inhibitor of kallikrein, partially inhibited the activity of SC5b-9. The
      permeabilizing factor(s) released after 30 min of incubation of endothelial cells
      with SC5b-9 caused a prompt leakage of albumin like BK. Intravital microscopy
      confirmed both the extravasation of circulating FITC-BSA across mesenteric
      microvessels 15 min after topical application of SC5b-9 and the complete
      neutralization by the mixture of HOE-140 and CV-3988. SC5b-9 induced opening of
      interendothelial junctions in mesenteric endothelium documented by transmission
      electron microscopy.

PMID- 15557189
TI  - A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B
      with implications for therapy in rheumatoid arthritis.
AB  - TNF-alpha is a key factor in a variety of inflammatory diseases. This study
      examines the role of p38 MAPK in the regulation of TNF-alpha in primary human
      cells relevant to inflammation, e.g., macrophages and rheumatoid synovial cells.
      Using a dominant negative variant (D168A) of p38 MAPK and a kinase inhibitor,
      SB203580, we confirm in primary human macrophages that p38 MAPK regulates TNF
      alpha production using a posttranscriptional mechanism requiring the 3'
      untranslated region of the gene. However, in LPS-activated primary human
      macrophages we also detect a second previously unidentified mechanism, the p38
      MAPK modulation of TNF-alpha transcription. This is mediated through p38 MAPK
      regulation of NF-kappaB. Interestingly this mechanism was not observed in
      rheumatoid synovial cells. Importantly however, the dominant negative mutant of
      p38 MAPK, but not SB203580 was effective at inhibiting spontaneous TNF-alpha
      production in these ex vivo rheumatoid synovial cell cultures. These data
      indicate there are potential major differences in the role of p38 MAPK in
      inflammatory signaling that have a bearing on the use of this kinase as a target
      for therapy. These results indicate despite disappointing results with p38 MAPK
      inhibitors in the clinic, this kinase is a valid target in rheumatoid disease.

PMID- 15557190
TI  - CCR1 and CC chemokine ligand 5 interactions exacerbate innate immune responses
      during sepsis.
AB  - CCR1 has previously been shown to play important roles in leukocyte trafficking,
      pathogen clearance, and the type 1/type 2 cytokine balance, although very little
      is known about its role in the host response during sepsis. In a cecal ligation
      and puncture model of septic peritonitis, CCR1-deficient (CCR1(-/-)) mice were
      significantly protected from the lethal effects of sepsis when compared with wild
      type (WT) controls. The peritoneal and systemic cytokine profile in CCR1(-/-)
      mice was characterized by a robust, but short-lived and regulated antibacterial
      response. CCR1 expression was not required for leukocyte recruitment, suggesting
      critical differences extant in the activation of WT and CCR1(-/-) resident or
      recruited peritoneal cells during sepsis. Peritoneal macrophages isolated from
      naive CCR1(-/-) mice clearly demonstrated enhanced cytokine/chemokine generation
      and antibacterial responses compared with similarly treated WT macrophages. CCR1
      and CCL5 interactions markedly altered the inflammatory response in vivo and in
      vitro. Administration of CCL5 increased sepsis-induced lethality in WT mice,
      whereas neutralization of CCL5 improved survival. CCL5 acted in a CCR1-dependent
      manner to augment production of IFN-gamma and MIP-2 to damaging levels. These
      data illustrate that the interaction between CCR1 and CCL5 modulates the innate
      immune response during sepsis, and both represent potential targets for
      therapeutic intervention.

PMID- 15557191
TI  - Interaction of soluble form of recombinant extracellular TLR4 domain with MD-2
      enables lipopolysaccharide binding and attenuates TLR4-mediated signaling.
AB  - TLRs have been implicated in recognition of pathogen-associated molecular
      patterns. TLR4 is a signaling receptor for LPS, but requires MD-2 to respond
      efficiently to LPS. The purposes of this study were to examine the interactions
      of the extracellular TLR4 domain with MD-2 and LPS. We generated soluble forms of
      rTLR4 (sTLR4) and TLR2 (sTLR2) lacking the putative intracellular and
      transmembrane domains. sTLR4 consisted of Glu(24)-Lys(631). MD-2 bound to sTLR4,
      but not to sTLR2 or soluble CD14. BIAcore analysis demonstrated the direct
      binding of sTLR4 to MD-2 with a dissociation constant of K(D) = 6.29 x 10(-8) M.
      LPS-conjugated beads precipitated MD-2, but not sTLR4. However, LPS beads
      coprecipitated sTLR4 and MD-2 when both proteins were coincubated. The addition
      of sTLR4 to the medium containing the MD-2 protein significantly attenuated LPS
      induced NF-kappaB activation and IL-8 secretion in wild-type TLR4-expressing
      cells. These results indicate that the extracellular TLR4 domain-MD-2 complex is
      capable of binding LPS, and that the extracellular TLR4 domain consisting of
      Glu(24)-Lys(631) enables MD-2 binding and LPS recognition to TLR4. In addition,
      the use of sTLR4 may lead to a new therapeutic strategy for dampening endotoxin
      induced inflammation.

PMID- 15557192
TI  - Prostaglandin E2 promotes the survival of bone marrow-derived dendritic cells.
AB  - Since dendritic cells (DC) participate in both innate and adaptive immunity,
      their survival and expansion is tightly controlled. Little is known about the
      mechanisms of DC apoptosis. PGE(2), an arachidonic acid metabolite, plays an
      essential role in DC migration. We propose a novel function for PGE(2) as a DC
      survival factor. Our studies demonstrate that PGE(2) protects DC in vitro against
      apoptosis induced by withdrawal of growth factors or ceramide. DC matured in
      conditions that inhibit endogenous PGE(2) release are highly susceptible to
      apoptosis and exogenous PGE(2) re-establishes the more resistant phenotype. The
      antiapoptotic effect is mediated through EP-2/EP-4 receptors and involves the
      PI3K --> Akt pathway. PGE(2) leads to increased phosphorylation of Akt,
      protection against mitochondrial membrane compromise, and decreased caspase 3
      activity. Macroarray data indicate that PGE(2) leads to the down-regulation of a
      number of proapoptotic molecules, i.e., BAD, several caspases, and granzyme B. In
      vivo, higher numbers of immature and Ag-loaded CFSE-labeled DC are present in the
      draining lymph nodes of mice inoculated with PGE(2) receptor agonists, compared
      with animals treated with ibuprofen or controls injected with PBS. This suggests
      that PGE(2) acts as an endogenous antiapoptotic factor for DC and raises the
      possibility of using PGE(2) agonists to increase the survival of Ag-loaded DC
      following in vivo administration.

PMID- 15557193
TI  - RhoA/Rho-associated kinase pathway selectively regulates thrombin-induced
      intercellular adhesion molecule-1 expression in endothelial cells via activation
      of I kappa B kinase beta and phosphorylation of RelA/p65.
AB  - We investigated the involvement of the RhoA/Rho-associated kinase (ROCK) pathway
      in regulating ICAM-1 expression in endothelial cells by the procoagulant,
      thrombin. Exposure of HUVECs to C3 exoenzyme, a selective inhibitor of Rho,
      markedly reduced thrombin-induced ICAM-1 expression. Inhibition of ROCK, the
      downstream effector of Rho, also prevented thrombin-induced ICAM-1 expression.
      Blockade of thrombin-induced ICAM-1 expression was secondary to inhibition of NF
      kappaB activity, the key regulator of ICAM-1 expression in endothelial cells. In
      parallel studies we observed that inhibition of the RhoA/ROCK pathway by the same
      pharmacological and genetic approaches failed to inhibit TNF-alpha-induced NF
      kappaB activation and ICAM-1 expression. The effect of RhoA/ROCK inhibition on
      thrombin-induced NF-kappaB activation was secondary to inhibition of IkappaB
      kinase activation and subsequent IkappaBalpha degradation and nuclear uptake and
      the DNA binding of NF-kappaB. Inhibition of the RhoA/ROCK pathway also prevented
      phosphorylation of Ser(536) within the transactivation domain 1 of NF-kappaB
      p65/RelA, a critical event conferring transcriptional competency to the bound NF
      kappaB. Thus, the RhoA/ROCK pathway signals thrombin-induced ICAM-1 expression
      through the activation of IkappaB kinase, which promotes NF-kappaB binding to
      ICAM-1 promoter and phosphorylation of RelA/p65, thus mediating the
      transcriptional activation of bound NF-kappaB.

PMID- 15557194
TI  - Lipopolysaccharide induces matrix metalloproteinase-9 expression via a
      mitochondrial reactive oxygen species-p38 kinase-activator protein-1 pathway in
      Raw 264.7 cells.
AB  - We have identified a novel signaling pathway that leads to expression of matrix
      metalloproteinase-9 (MMP-9) in murine macrophages in response to the bacterial
      endotoxin, LPS. We showed that p38 kinase was essential for this induction and
      observed that LPS-induced MMP-9 expression was sensitive to rottlerin, a putative
      protein kinase Cdelta (PKCdelta) inhibitor. However neither infection with a
      retrovirus expressing a dominant negative mutant of PKCdelta nor down-regulation
      of PKCdelta by prolonged PMA treatment affected MMP-9 expression, thus excluding
      involvement of PKCdelta. Interestingly, LPS-induced MMP-9 expression and p38
      kinase phosphorylation were shown to be suppressed by the antioxidant N
      acetylcysteine and the flavoenzyme inhibitor diphenyleneiodonium chloride, but
      not by pyrrolidine dithiocarbamate, an NF-kappaB inhibitor. In addition, LPS was
      found to induce the production of mitochondrial reactive oxygen species (ROS) and
      this effect was rottlerin-sensitive, suggesting an inhibitory effect of rottlerin
      on mitochondrial ROS. LPS-induced MMP-9 expression and p38 kinase phosphorylation
      were also inhibited by rotenone, a specific inhibitor of mitochondrial complex I,
      supporting the role of mitochondrial ROS in LPS signaling to MMP-9. Finally, we
      showed that the ROS-p38 kinase cascade targets the transcription factor AP-1.
      Taken together, our findings identify a ROS-p38 kinase-AP-1 cascade as a novel
      pathway mediating LPS signaling to MMP-9 expression in macrophages.

PMID- 15557195
TI  - Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune
      encephalomyelitis.
AB  - Nogo-66, the extracellular 66 aa loop of the Nogo-A protein found in CNS myelin,
      interacts with the Nogo receptor and has been proposed to mediate inhibition of
      axonal regrowth. It has been shown that immunization with Nogo-A promotes
      recovery in animal models of spinal cord injury through induction of Ab
      production. In this report, studies were performed to characterize the immune
      response to Nogo-66 and to determine the role of Nogo in experimental autoimmune
      encephalomyelitis (EAE). Immunization of EAE-susceptible mouse strains with
      peptides derived from Nogo-66 induced a CNS immune response with clinical and
      pathological similarities to EAE. The Nogo-66 peptides elicited strong T cell
      responses that were not cross-reactive to other encephalitogenic myelin Ags.
      Using a large scale spotted microarray containing proteins and peptides derived
      from a wide spectrum of myelin components, we demonstrated that Nogo-66 peptides
      also generated a specific Ab response that spreads to several other
      encephalitogenic myelin Ags following immunization. Nogo-66-specific T cell lines
      ameliorated established EAE, via Nogo-66-specific Th2 cells that entered the CNS.
      These results indicate that some T cell and B cell immune responses to Nogo-66
      are associated with suppression of ongoing EAE, whereas other Nogo-66 epitopes
      can be encephalitogenic.

PMID- 15557196
TI  - Involvement of eotaxin, eosinophils, and pancreatic predisposition in development
      of type 1 diabetes mellitus in the BioBreeding rat.
AB  - Allergy and autoimmunity are both examples of deregulated immunity characterized
      by inflammation and injury of targeted tissues that have until recently been
      considered disparate disease processes. However, recent findings have implicated
      mast cells, in coordination with granulocytes and other immune effector cells, in
      the pathology of these two disorders. The BioBreeding (BB) DRlyp/lyp rat develops
      an autoimmune insulin-dependent diabetes similar to human type 1 diabetes
      mellitus (T1DM), whereas the BBDR+/+ rat does not. To better understand immune
      processes during development of T1DM, gene expression profiling at day (d) 40
      (before insulitis) and d65 (before disease onset) was conducted on pancreatic
      lymph nodes of DRlyp/lyp, DR+/+, and Wistar-Furth (WF) rats. The eosinophil
      recruiting chemokine, eotaxin, and the high-affinity IgE receptor (FcepsilonRI)
      were up-regulated >5-fold in d65 DRlyp/lyp vs d65 DR+/+ pancreatic lymph nodes by
      microarray (p < 0.05) and quantitative RT-PCR studies (p < 0.05). DR+/+, WF, and
      d40 DRlyp/lyp animals possessed normal pancreatic histology; however, d65
      DRlyp/lyp animals possessed eosinophilic insulitis. Therefore,
      immunohistochemistry for pancreatic eotaxin expression was conducted, revealing
      positive staining of d65 DRlyp/lyp islets. Islets of d65 DR+/+ rats also stained
      positively, consistent with underlying diabetic predisposition in the BB lineage,
      whereas WF islets did not. Other differentially expressed transcripts included
      those associated with eosinophils, mast cells, and lymphocytes. These data
      support an important role for these inflammatory mediators in BB rat T1DM and
      suggest that the lymphopenia due to the Ian5/(lyp) mutation may result in a
      deregulation of cells involved in insulitis and beta cell destruction.

PMID- 15557197
TI  - NF-kappa B activation in airways modulates allergic inflammation but not
      hyperresponsiveness.
AB  - Airways display robust NF-kappaB activation and represent targets for anti
      inflammatory asthma therapies, but the functional importance of NF-kappaB
      activation in airway epithelium remains enigmatic. Therefore, transgenic mice
      were created in which NF-kappaB activation is repressed specifically in airways
      (CC10-IkappaBalpha(SR) mice). In response to inhaled Ag, transgenic mice
      demonstrated significantly ameliorated inflammation, reduced levels of
      chemokines, T cell cytokines, mucus cell metaplasia, and circulating IgE compared
      with littermate controls. Despite these findings, Ag-driven airways
      hyperresponsiveness was not attenuated in CC10-IkappaBalpha(SR) mice. This study
      clearly demonstrates that airway epithelial NF-kappaB activation orchestrates Ag
      induced inflammation and subsequent adaptive immune responses, but does not
      contribute to airways hyperresponsiveness, the cardinal feature that underlies
      asthma.

PMID- 15557198
TI  - Inhibition of fractalkine ameliorates murine collagen-induced arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with
      massive infiltration of inflammatory cells in the synovium of multiple joints. We
      and others have shown that fractalkine (FKN/CX3CL1), a chemokine expressed on
      fibroblast-like synoviocytes and endothelial cells in RA synovium, may contribute
      to the accumulation of T cells, macrophages, and dendritic cells, which express
      CX3CR1, the receptor for FKN. This interaction might be involved in adhesion of
      the inflammatory cells to endothelial cells, migration into the synovium, and
      cytokine production. In this study, we examined the effect of FKN inhibition on
      murine collagen-induced arthritis. Anti-FKN mAb significantly lowered clinical
      arthritis score compared with control Ab, and reduced infiltration of
      inflammatory cells and bone erosion in the synovium. However, anti-FKN mAb did
      not affect the production of either serum anti-collagen type II (CII) IgG or IFN
      gamma by CII-stimulated splenic T cells. Furthermore, treatment with anti-FKN mAb
      inhibited migration of adoptively transferred splenic macrophages into the
      inflamed synovium. Our results suggest that anti-FKN mAb ameliorates arthritis by
      inhibiting infiltration of inflammatory cells into the synovium. Thus, FKN can be
      a new target molecule for the treatment of RA.

PMID- 15557199
TI  - CXC chemokine ligand 10 neutralization suppresses the occurrence of diabetes in
      nonobese diabetic mice through enhanced beta cell proliferation without affecting
      insulitis.
AB  - We have shown that neutralization of IFN-inducible protein 10/CXCL10, a chemokine
      for Th1 cells, breaks Th1 retention in the draining lymph nodes, resulting in
      exacerbation in Th1-dominant autoimmune disease models induced by immunization
      with external Ags. However, there have been no studies on the role of CXCL10
      neutralization in Th1-dominant disease models induced by constitutive intrinsic
      self Ags. So, we have examined the effect of CXCL10 neutralization using a type 1
      diabetes model initiated by developmentally regulated presentation of beta cell
      Ags. CXCL10 neutralization suppressed the occurrence of diabetes after
      administration with cyclophosphamide in NOD mice, although CXCL10 neutralization
      did not significantly inhibit insulitis and gave no influence on the trafficking
      of effector T cells into the islets. Because both CXCL10 and CXCR3 were,
      unexpectedly, coexpressed on insulin-producing cells, CXCL10 was considered to
      affect mature and premature beta cells in an autocrine and/or paracrine fashion.
      In fact, CXCL10 neutralization enhanced proliferative response of beta cells and
      resultantly increased beta cell mass without inhibiting insulitis. Thus, CXCL10
      neutralization can be a new therapeutic target for beta cell survival, not only
      during the early stage of type 1 diabetes, but also after islet transplantation.

PMID- 15557200
TI  - Combinations of anti-LFA-1, everolimus, anti-CD40 ligand, and allogeneic bone
      marrow induce central transplantation tolerance through hemopoietic chimerism,
      including protection from chronic heart allograft rejection.
AB  - Central transplantation tolerance through hemopoietic chimerism initially
      requires inhibition of allogeneic stem cell or bone marrow (BM) rejection, as
      previously achieved in murine models by combinations of T cell costimulation
      blockade. We have evaluated LFA-1 blockade as part of regimens to support mixed
      hemopoietic chimerism development upon fully allogeneic BALB/c BM transfer to
      nonirradiated busulfan-treated B6 recipient mice. Combining anti-LFA-1 with anti
      CD40 ligand (CD40L) induced high incidences and levels of stable multilineage
      hemopoietic chimerism comparable to chimerism achieved with anti-CD40L and
      everolimus (40-O-(2-hydroxyethyl)-rapamycin) under conditions where neither Ab
      alone was effective. The combination of anti-LFA-1 with everolimus also resulted
      in high levels of chimerism, albeit with a lower incidence of stability.
      Inhibition of acute allograft rejection critically depended on chimerism
      stability, even if maintained at very low levels around 1%, as was the case for
      some recipients without busulfan conditioning. Chimerism stability correlated
      with a significant donor BM-dependent loss of host-derived Vbeta11(+) T cells 3
      mo after BM transplantation (Tx). Combinations of anti-CD40L with anti-LFA-1 or
      everolimus also prevented acute rejection of skin allografts transplanted before
      established chimerism, albeit not independently of allospecific BMTx. All skin
      and heart allografts transplanted to stable chimeras 3 and 5 mo after BMTx,
      respectively, were protected from acute rejection. Moreover, this included
      prevention of heart allograft vascular intimal thickening ("chronic rejection").

PMID- 15557201
TI  - Tracking of proinflammatory collagen-specific T cells in early and late collagen
      induced arthritis in humanized mice.
AB  - Rheumatoid arthritis is a chronic inflammatory disease associated with certain
      HLA-DR4 subtypes. The target autoantigen(s) is unknown, but type II collagen
      (CII) is a candidate, with a single immunodominant DR4-restricted 261-273 T cell
      epitope (CII(261-273)). In the present study, we have prepared HLA-DR4:CII(261
      273) tetramers and analyzed peripheral blood, lymph node, and synovial fluid
      cells from DR4-transgenic mice with early and late collagen-induced arthritis to
      draw a fuller picture of the role of CII-reactive Th cells in disease
      development. Their frequencies increased approximately 20-fold in blood 1-2 wk
      postimmunization, and even more in acutely arthritic joints. Our data strongly
      suggest that CII-specific Th cells are necessary, but not sufficient for collagen
      induced arthritis. The CII-specific Th cells displayed an activated
      proinflammatory Th1 phenotype, and their expansion correlated with onset and
      severity of arthritis and also with anti-CII Ab levels. Surprisingly, shortly
      after the first clinical signs of arthritis, activated HLA-DR4:CII tetramer(+)
      cells became undetectable in the synovial fluid and rare in the blood, but
      persisted in lymph nodes. Consequently, future human studies should focus on
      patients with early arthritis, and on their synovial cells, to re-evaluate the
      occurrence and pathogenic importance of CII-specific or other Th cells in
      rheumatoid arthritis.

PMID- 15557202
TI  - A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an
      unconventional open reading frame of human TMSB4Y gene.
AB  - Female-to-male hemopoietic stem cell transplantation (HSCT) elicits T cell
      responses against male-specific minor histocompatibility (H-Y) Ags encoded by the
      Y chromosome. All previously identified H-Y Ags are encoded by conventional open
      reading frames, but we report in this study the identification of a novel H-Y Ag
      encoded in the 5'-untranslated region of the TMSB4Y gene. An HLA-A*3303
      restricted CD8(+) CTL clone was isolated from a male patient after an HSCT from
      his HLA-identical sister. Using a panel of cell lines carrying Y chromosome
      terminal deletions, a narrow region controlling the susceptibility of these
      target cells to CTL recognition was localized. Minigene transfection and epitope
      reconstitution assays identified an 11-mer peptide, EVLLRPGLHFR, designated
      TMSB4Y/A33, whose first amino acid was located 405 bp upstream of the TMSB4Y
      initiation codon. Analysis of the precursor frequency of CTL specific for
      recipient minor histocompatibility Ags in post-HSCT peripheral blood T cells
      revealed that a significant fraction of the total donor CTL response in this
      patient was directed against the TMSB4Y epitope. Tetramer analysis continued to
      detect TMSB4Y/A33-specific CD8(+) T cells at least up to 700 days post-HSCT. This
      finding underscores the in vivo immunological relevance of minor
      histocompatibility Ags derived from unconventional open reading frame products.

PMID- 15557203
TI  - Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced
      injury in complement receptor 2/complement receptor 1-deficient mice.
AB  - Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric
      ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab
      repertoire. Neither the nature of the Abs that are involved in I/R injury nor the
      composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice,
      is known. Because anti-phospholipid Abs have been shown to mediate fetal growth
      retardation and loss when injected into pregnant mice, we performed experiments
      to determine whether anti-phospholipid Abs can also reconstitute I/R injury and,
      therefore, represent members of the injury-inducing repertoire that is missing in
      Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and
      polyclonal Abs against negatively charged phospholipids can reconstitute
      mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In
      addition, Abs against beta2 glycoprotein I restore local and remote tissue damage
      in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage
      in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2
      glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs
      can bind to tissues subjected to I/R insult and mediate tissue damage.

PMID- 15557204
TI  - Self-reactive T cell receptor-reactive CD8+ T cells inhibit T cell lymphoma
      growth in vivo.
AB  - Syngenic C57BL/6 mice (H-2(b)) vaccinated with mitomycin C-treated L12R4 T
      lymphoma cells develop protective immunity toward the MHC class II-negative tumor
      cells. In the present study, we characterize the nature, mode of function, and
      specificity of the effector cells in this immunity. These cells are TCR-specific
      CD8(+) T lymphocytes with effector function in vitro as well as in vivo upon
      transfer to naive mice. They produce high levels of IFN-gamma and TNF-alpha, but
      little or no IL-4. By means of TCRbeta-negative variant L12R4 cells, P3.3, and
      TCR-Vbeta2 cDNA-transfected and TCR-Vbeta2-expressing P3.3 lymphoma cells, we
      found that a significant part of the effector T cells are specific for the
      Vbeta12 region. The growth inhibition of L12R4 cells in vitro was inhibited by
      anti-H-2, anti-K(b), and anti-D(b) mAb. Furthermore, vaccination with Vbeta12
      peptide p67-78, which binds to both K(b) and D(b) MHC class I molecules, induces
      partial protection against L12R4 T lymphoma cells. Thus, self-reactive TCR-Vbeta
      specific, K(b)-, or D(b)-restricted CD8(+) T cells mediate inhibition of T cell
      lymphoma growth in vitro and in vivo.

PMID- 15557205
TI  - TLR4 contributes to disease-inducing mechanisms resulting in central nervous
      system autoimmune disease.
AB  - Environmental factors strongly influence the development of autoimmune diseases,
      including multiple sclerosis. Despite this clear association, the mechanisms
      through which environment mediates its effects on disease are poorly understood.
      Pertussis toxin (PTX) functions as a surrogate for environmental factors to
      induce animal models of autoimmunity, such as experimental autoimmune
      encephalomyelitis. Although very little is known about the molecular mechanisms
      behind its function in disease development, PTX has been hypothesized to
      facilitate immune cell entry to the CNS by increasing permeability across the
      blood-brain barrier. Using intravital microscopy of the murine
      cerebromicrovasculature, we demonstrate that PTX alone induces the recruitment of
      leukocytes and of active T cells to the CNS. P-selectin expression was induced by
      PTX, and leukocyte/endothelial interactions could be blocked with a P-selectin
      blocking Ab. P-selectin blockade also prevented PTX-induced increase in
      permeability across the blood-brain barrier. Therefore, permeability is a
      secondary result of recruitment, rather than the primary mechanism by which PTX
      induces disease. Most importantly, we show that PTX induces intracellular signals
      through TLR4, a receptor intimately associated with innate immune mechanisms. We
      demonstrate that PTX-induced leukocyte recruitment is dependent on TLR4 and give
      evidence that the disease-inducing mechanisms initiated by PTX are also at least
      partly dependent on TLR4. We propose that this innate immune pathway is a novel
      mechanism through which environment can initiate autoimmune disease of the CNS.

PMID- 15557206
TI  - Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice
      results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity.
AB  - An intranasal DNA vaccine prime followed by a gp41 peptide booster immunization
      was compared with gp41 peptide and control immunizations. Serum HIV-1-specific
      IgG and IgA as well as IgA in feces and vaginal and lung secretions were detected
      after immunizations. Long-term humoral immunity was studied for up to 12 mo after
      the booster immunization by testing the presence of HIV-1 gp41- and CCR5-specific
      Abs and IgG/IgA-secreting B lymphocytes in spleen and regional lymph nodes in
      immunized mice. A long-term IgA-specific response in the intestines, vagina, and
      lungs was obtained in addition to a systemic immune response. Mice immunized only
      with gp41 peptides and L3 adjuvant developed a long-term gp41-specific serum IgG
      response systemically, although over a shorter period (1-9 mo), and long-term
      mucosal gp41-specific IgA immunity. HIV-1-neutralizing serum Abs were induced
      that were still present 12 mo after booster immunization. HIV-1 SF2-neutralizing
      fecal and lung IgA was detectable only in the DNA-primed mouse groups. Intranasal
      DNA prime followed by one peptide/L3 adjuvant booster immunization, but not a
      peptide prime followed by a DNA booster, was able to induce B cell memory and HIV
      1-neutralizing Abs for at least half of a mouse's life span.

PMID- 15557207
TI  - Residues Met89 and Ser160 in the human equilibrative nucleoside transporter 1
      affect its affinity for adenosine, guanosine, S6-(4-nitrobenzyl)-mercaptopurine
      riboside, and dipyridamole.
AB  - The human equilibrative nucleoside transporter 1 (hENT1) is an important
      modulator of the physiological action of adenosine. We identified amino acid
      residues involved in adenosine transport using a yeast-based assay to rapidly
      screen and identify randomly generated hENT1 mutants that exhibited decreased
      sensitivity to inhibition of adenosine transport by various hENT1 competitive
      inhibitors. We identified Met89 and Ser160 as important in the affinity of hENT1
      for various substrates and inhibitors. Mutation to Met89Cys or Ser160Cys
      significantly (p < 0.05) increased the S6-(4-nitrobenzyl)-mercaptopurine riboside
      (NBMPR) IC50 values by approximately 4- and 6-fold, respectively (42 +/- 13 and
      65 +/- 1.6 nM) compared with the wild-type transporter (11 +/- 0.7 nM). The
      double mutant Met89Cys/Ser160Cys synergistically increased the NBMPR IC50 value
      to approximately 19-fold of that of the wild-type transporter. In contrast,
      compared with wild-type hENT1, the sensitivity to dipyridamole inhibition was
      significantly (p < 0.05) increased by only the Ser160Cys (approximately 2.6-fold)
      or the double mutant Met89Cys/Ser160Cys (approximately 4.7-fold) but not by the
      Met89Cys mutant. Mutation to Met89Cys or Ser160Cys increased the Km of adenosine
      (approximately 8- and 3-fold) and the Ki of guanosine (approximately 6- and 2
      fold). The double mutant increased both the Km value of adenosine and the Ki
      value of guanosine by approximately 8-fold and seemed to confer no additional
      reduction in adenosine or guanosine affinity than that by mutation of Met89
      alone. Together, these data indicate that transmembrane domains (TMDs) 2 (Met89)
      and 4 (Ser160) of hENT1 interact and are important in conferring sensitivity to
      NBMPR. In contrast, Ser160 and Met89 of hENT1, respectively, play a dominant role
      in conferring sensitivity to dipyridamole and adenosine/guanosine affinity.

PMID- 15557208
TI  - Intracellular hyaluronan in arterial smooth muscle cells: association with
      microtubules, RHAMM, and the mitotic spindle.
AB  - Although considered a pericellular matrix component, hyaluronan was recently
      localized in the cytoplasm and nucleus of proliferating cells, supporting earlier
      reports that hyaluronan was present in locations such as the nucleus, rough
      endoplasmic reticulum, and caveolae. This suggests that it can play roles both
      inside and outside the cell. Hyaluronan metabolism is coupled to mitosis and cell
      motility, but it is not clear if intracellular hyaluronan associates with
      cytoskeletal elements or plays a structural role. Here we report the distribution
      of intracellular hyaluronan, microtubules, and RHAMM in arterial smooth muscle
      cells in vitro. The general distribution of intracellular hyaluronan more closely
      resembled microtubule staining rather than actin filaments. Hyaluronan was
      abundant in the perinuclear microtubule-rich areas and was present in lysosomes,
      other vesicular structures, and the nucleolus. Partially fragmented fluorescein
      hyaluronan was preferentially translocated to the perinuclear area compared with
      high-molecular-weight hyaluronan. In the mitotic spindle, hyaluronan colocalized
      with tubulin and with the hyaladherin RHAMM, a cell surface receptor and
      microtubule-associated protein that interacts with dynein and maintains spindle
      pole stability. Internalized fluorescein-hyaluronan was also seen at the spindle.
      Following telophase, an abundance of hyaluronan near the midbody microtubules at
      the cleavage furrow was also noted. In permeabilized cells, fluorescein
      hyaluronan bound to RHAMM-associated microtubules. These findings suggest novel
      functions for hyaluronan in cellular physiology.

PMID- 15557209
TI  - Combined smooth muscle and melanocytic differentiation in
      lymphangioleiomyomatosis.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is characterized by abnormal
      proliferation of immature-looking smooth muscle (SM)-like cells (LAM cells),
      leading to lung destruction and cyst formation. In addition to expressing some SM
      markers, scattered LAM cells express the melanocytic maker gp100, which is
      recognized by antibody HMB45, suggesting that at least a few LAM cells may have
      melanocytic differentiation. Here we immunostained 26 LAM samples for several
      melanocyte-related proteins. These studies showed that all LAM cells express
      tetraspanin CD63, a melanoma-associated protein that belongs to the transmembrane
      4 superfamily. The majority of LAM cells also immunoreacted with PNL2, an
      antibody against a yet uncharacterized melanocytic antigen. Furthermore, we
      examined the co-expression of PNL2 and Ki-67, an indicator of cell proliferation,
      and found that PNL2-positive LAM cells showed a significantly lower proliferation
      rate compared with their negative counterparts. Our findings shed new light on
      the nature of the LAM cells by demonstrating their combined SM and melanocytic
      differentiation and the existence of subpopulations with different proliferative
      potential. Furthermore, these studies provided two new antibodies useful in the
      diagnosis of LAM.

PMID- 15557210
TI  - Immunolocalization of actin in Paramecium cells.
AB  - We have selected a conserved immunogenic region from several actin genes of
      Paramecium, recently cloned in our laboratory, to prepare antibodies for Western
      blots and immunolocalization. According to cell fractionation analysis, most
      actin is structurebound. Immunofluorescence shows signal enriched in the cell
      cortex, notably around ciliary basal bodies (identified by anti-centrin
      antibodies), as well as around the oral cavity, at the cytoproct and in
      association with vacuoles (phagosomes) up to several mum in size. Subtle strands
      run throughout the cell body. Postembedding immunogold labeling/EM analysis shows
      that actin in the cell cortex emanates, together with the infraciliary lattice,
      from basal bodies to around trichocyst tips. Label was also enriched around
      vacuoles and vesicles of different size including "discoidal" vesicles that serve
      the formation of new phagosomes. By all methods used, we show actin in cilia.
      Although none of the structurally well-defined filament systems in Paramecium are
      exclusively formed by actin, actin does display some ordered, though not very
      conspicuous, arrays throughout the cell. F-actin may somehow serve vesicle
      trafficking and as a cytoplasmic scaffold. This is particularly supported by the
      postembedding/EM labeling analysis we used, which would hardly allow for any
      large-scale redistribution during preparation.

PMID- 15557211
TI  - Ultrastructural localization of caspase-14 in human epidermis.
AB  - Caspase-14 has been implicated in the formation of stratum corneum because of its
      specific expression and activation in terminally differentiating keratinocytes.
      However, its precise physiological role and its protein substrate are elusive. We
      studied the ultrastructural localization of caspase-14 in human epidermis to
      compare its distribution pattern with that of well-characterized differentiation
      markers. Immunogold cytochemistry confirmed that caspase-14 is nearly absent in
      basal and spinous layers. In the granular, layer nuclei and keratohyalin granules
      were labeled with increasing intensity towards the transitional layer.
      Particularly strong caspase-14 labeling was associated with areas known to be
      occupied by involucrin and loricrin, whereas F-granules, occupied by
      profilaggrin/filaggrin, were much less labeled. A high density of gold particles
      was also present at the forming cornified cell envelope, including desmosomes. In
      corneocytes, intense labeling was both cytoplasmic and associated with nuclear
      remnants and corneodesmosomes. These observations will allow focusing efforts of
      biochemical substrate screening on a subset of proteins localizing to distinct
      compartments of terminally differentiated keratinocytes.

PMID- 15557212
TI  - Essential contribution of tumor-derived perlecan to epidermal tumor growth and
      angiogenesis.
AB  - As a major heparan sulfate proteoglycan (PG) in basement membranes, perlecan has
      been linked to tumor invasion, metastasis, and angiogenesis. Here we produced
      epidermal tumors in immunocompromised rats by injection of mouse RT101 tumor
      cells. Tumor sections stained with species-specific perlecan antibodies, together
      with immunoelectron microscopy, showed that perlecan distributed around blood
      vessels was of both host and tumor cell origin. Tumor-derived perlecan was also
      distributed throughout the tumor matrix. Blood vessels stained with rat-specific
      PECAM-1 antibody showed their host origin. RT101 cells also expressed two other
      basement membrane heparan sulfate PGs, agrin and type XVIII collagen. Antisense
      targeting of perlecan inhibited tumor cell growth in vitro, while exogenous
      recombinant perlecan, but not heparin, restored the growth of antisense perlecan
      expressing cells, suggesting that perlecan core protein, rather than heparan
      sulfate chains from perlecan, agrin, or type XVIII collagen, regulates tumor cell
      growth. However, perlecan core protein requirement was not related to fibroblast
      growth factor-7 binding because RT101 cells were unresponsive to and lacked
      receptors for this growth factor. In vivo, antisense perlecan-transfected cells
      generated no tumors, whereas untransfected and vector-transfected cells formed
      tumors with obvious neovascularization, suggesting that tumor perlecan rather
      than host perlecan controls tumor growth and angiogenesis.

PMID- 15557213
TI  - A tracer study with systemically and locally administered dinitrophenylated
      osteopontin.
AB  - Osteopontin (OPN), a major non-collagenous matrix protein of bone, is also found
      in tissue fluids and in the circulation. It is still not clear whether
      circulating OPN contributes to bone formation. To elucidate this question, rat
      OPN was tagged with dinitrophenol groups and administered to rats either
      intravenously or by infusion with an osmotic minipump through a "surgical window"
      in the bone of the hemimandible. Dinitrophenylated rat albumin (ALB) was used as
      a control. The presence and distribution of tagged proteins were revealed by
      immunogold labeling on sections of tibia and alveolar bone. Tagged molecules of
      OPN were found in mineralization foci, surfaces and interfaces, and matrix
      accumulations among calcified collagen fibrils. Even though dinitrophenylated ALB
      was administered at several-fold higher concentrations, it did not accumulate in
      these sites. These results show that circulating OPN can be incorporated into
      specific compartments of forming bone and suggest that such molecules may play a
      more important role than previously suspected.

PMID- 15557214
TI  - Nucleolar size and activity are related to pRb and p53 status in human breast
      cancer.
AB  - Cell proliferation is tightly coordinated with cell growth. The oncosuppressor
      proteins pRb and p53 may exert a key role in coupling growth and proliferation by
      controlling both ribosome biogenesis and cell cycle progression. In the present
      study we evaluated the relationship between the pRb and p53 status and rRNA
      transcriptional activity in histological sections of 343 human primary breast
      carcinomas. Ribosomal biogenesis was quantified by morphometric analysis of
      silver-stained interphase nucleolar organizer regions (AgNORs). pRb and p53
      status was assessed by immunohistochemistry. Twenty-four tumors were considered
      to be pRb deleted, 260 tumors showed a phosphorylated-pRb labeling index (LI) up
      to 25%, and 55 tumors an LI >25%. Tumors with deleted pRb or phosphorylated-pRb
      LI > or =25% were characterized by significantly greater mean AgNOR area values
      than those with unaltered pRb (p<0.001). In the 71 tumors with mutated p53 the
      NOR area mean value was greater than in the 272 tumors with normal p53 (p<0.001).
      Our results demonstrate, for the first time in vivo, that pRb and p53 status is
      related to the ribosome biogenesis rate and suggest that in tumors with altered
      pRb and p53 function the up-regulation of rRNA synthesis may always assure an
      adequate growth to cancer cells with uncontrolled cell cycle progression.

PMID- 15557215
TI  - Pattern of expression of HtrA1 during mouse development.
AB  - The human HtrA family of proteases consists of four members: HtrA1, HtrA2, HtrA3,
      and HtrA4. In humans the four HtrA homologues appear to be involved in several
      important functions such as cell growth, apoptosis, and inflammatory reactions,
      and they control cell fate via regulated protein metabolism. In previous studies
      it was shown that the expression of HtrA1 was ubiquitous in normal adult human
      tissues. Here we examined the expression of HtrA1 protein and its corresponding
      mRNA during mouse embryogenesis using Northern blotting hybridization, RT-PCR,
      and immunohistochemical staining analyses. Our results indicate that HtrA1 is
      expressed in a variety of tissues in mouse embryos. Furthermore, this expression
      is regulated in a spatial and temporal manner. Relatively low levels of HtrA1
      mRNA are detected in embryos at the beginning of organogenesis (E8), and the
      levels of expression increase during late organogenesis (E14-E19). Our results
      show that HtrA1 was expressed during embryonic development in specific areas
      where signaling by TGFbeta family proteins plays important regulatory roles. The
      expression of HtrA1, documented both at mRNA and protein levels by RT-PCR and
      immunohistochemistry in the developing nervous system, is consistent with a
      possible role of this protein both in dividing and postmitotic neurons, possibly
      via its documented inhibitory effects on TGFbeta proteins. An exhaustive
      knowledge of the different cell- and tissue-specific patterns of expression of
      HtrA1 in normal mouse embryos is essential for a critical evaluation of the exact
      role played by this protein during development.

PMID- 15557216
TI  - Immersion autometallography: histochemical in situ capturing of zinc ions in
      catalytic zinc-sulfur nanocrystals.
AB  - In the mid-1980s, two versions of Timm's original immersion sulfide silver method
      were published. The authors used immersion of tissue in a sulfide solution as
      opposed to Timm, who used immersion of tissue blocks in hydrogen sulfide-bubbled
      alcohol. The autometallography staining resulting from the "sulfide only
      immersion" was not particularly impressive, but the significance of this return
      to an old approach became obvious when Wenzel and co-workers presented their
      approach in connection with introduction by the Palmiter group of zinc
      transporter 3 (ZnT3). The Wenzel/Palmiter pictures are the first high-resolution,
      high-quality pictures taken from tissues in which free and loosely bound zinc
      ions have been captured in zinc-sulfur nanocrystals by immersion. The trick was
      to place formalin-fixed blocks of mouse brains in a solution containing 3%
      glutaraldehyde and 0.1% sodium sulfide, ingredients used for transcardial
      perfusion in the zinc-specific NeoTimm method. That the NeoTimm technique results
      in silver enhancement of zinc-sulfur nanocrystals has been proved by proton
      induced X-ray multielement analyses (PIXE) and in vivo chelation with
      diethyldithiocarbamate (DEDTC). The aims of the present study were (a) to make
      the immersion-based capturing of zinc ions in zinc-sulfur nanocrystals work
      directly on sections and slices of fixed brain tissue, (b) to work out protocols
      that ensure zinc specificity and optimal quality of the staining, (c) to apply
      "immersion autometallography" (iZnSAMG) to other tissues that contain zinc
      enriched (ZEN) cells, and (d) to make the immersion approach work on unfixed
      fresh tissue.

PMID- 15557217
TI  - Expression and function of tight junctions in the crypt epithelium of human
      palatine tonsils.
AB  - The human palatine tonsils have surface and crypt stratified epithelium and may
      be initiated via the epithelium to mount immune responses to various presenting
      antigens. Here we investigated the expression and function of tight junctions in
      the epithelium of human palatine tonsils from patients with tonsillar hypertrophy
      or recurrent tonsillitis. Occludin, ZO-1, JAM-1, and claudin-1, -3, -4, -7, -8,
      and -14 mRNAs were detected in tonsillar hypertrophy. Occludin and claudin-14
      were expressed in the uppermost layer of the tonsil surface epithelium, whereas
      ZO-1, JAM-1, and claudin-1, -4, and -7 were found throughout the epithelium. In
      the crypt epithelium, claudin-4 was preferentially expressed in the upper layers.
      In freeze-fracture replicas, short fragments of continuous tight junction strands
      were observed but never formed networks. In the crypt epithelium of recurrent
      tonsillitis, the tracer was leaked from the surface regions where occludin and
      claudin-4 disappeared. Occludin, ZO-1, JAM-1, and claudin-1, -3, -4, and -14, but
      not claudin-7, mRNAs were decreased in recurrent tonsillitis compared with those
      of tonsillar hypertrophy. These studies suggest unique expression of tight
      junctions in human palatine tonsillar epithelium, and the crypt epithelium may
      possess an epithelial barrier different from that of the surface epithelium.

PMID- 15557218
TI  - Bovine Doppel (Dpl) and prion protein (PrP) expression on lymphoid tissue and
      circulating leukocytes.
AB  - Doppel (Dpl) protein shares some structural features with prion protein (PrP),
      whose pathologic isoform (PrPsc) is considered to be the causative agent of
      transmissible spongiform encephalopathies. Dpl is mainly expressed in testes but,
      when ectopically expressed in the central nervous system, is neurotoxic. We have
      examined the expression pattern of Dpl and PrP on bovine lymphoid tissues and
      circulating leukocytes. A polyclonal anti-Dpl antibody along with a panel of
      monoclonal antibodies specific for leukocyte membrane antigens or PrP were used
      to examine frozen sections from spleen, lymph nodes, and bone marrow by
      immunohistochemistry. Blood was analyzed by flow cytometry. Double staining was
      used to study the possible coexpression of the two proteins and to characterize
      cells expressing Dpl and/or PrP. Dpl was expressed in B-cells, in dendritic cells
      within lymphoid follicles, bone marrow, circulating myeloid cells, and
      circulating B-cells. The distribution of Dpl was quite similar to that of PrP.
      The only differences in expression observed concerned the low number of Dpl+
      cells in lymph nodes and the strong Dpl positivity of circulating granulocytes.
      The two proteins were rarely co-expressed, suggesting an independent expression
      mechanism in resting cells. The role of Dpl+ leukocytes in the pathogenesis of
      Dpl- or PrP-induced diseases merits further investigation.

PMID- 15557219
TI  - Subapical localization of the dopamine D3 receptor in proximal tubules of the rat
      kidney.
AB  - The dopamine D3 receptor (D3R), intensively studied in neuroscience, also plays
      an important role in the regulation of renal and cardiovascular function. In
      contrast to functional findings, less information is available on its
      localization in the kidney. Neither RT-PCR studies nor radioligand binding assays
      are suitable to selectively determine the distribution of renal D3R at the level
      of cellular or even subcellular structures. We studied the renal D3R distribution
      in Sprague-Dawley rats by a polyclonal antiserum directed against an epitope in
      the third intracytoplasmic loop. D3R immunoreactivity was detected by indirect
      immunofluorescence and confocal laser scanning microscopy. D3R staining was
      confined to the renal cortex and occurred in proximal convoluted tubules near or
      in direct connection with the urinary pole of the glomeruli. The fluorescent
      spots were restricted to the subapical portion of the proximal tubular cells.
      Double staining with the F-actin marker phalloidin revealed a localization of the
      D3R below the brush border region. However, staining by anti-beta1/beta2
      adaptins, recognizing clathrin-coated compartments, did not correspond to the
      distribution of the D3R signal. This is the first description of a D3R
      accumulation in a cytoplasmic pool in the kidney, probably corresponding to a
      recycling mechanism or storage compartment.

PMID- 15557220
TI  - Immunohistochemical characterization of cloned lamb nephropathy.
AB  - Kidneys from lambs derived by nuclear transfer are frequently abnormal and are
      characterized by an enlarged pelvis and narrow medulla, consistent with lower
      urinary tract obstruction and development of variable hydronephrosis. The precise
      pathogenesis of this entity is unknown. Immunohistochemical staining for
      intermediate filaments was used to further characterize the lesions seen in this
      condition and was compared with age-matched control tissue. Major findings were
      upregulation of cytokeratin on damaged tubules, desmin and vimentin in
      undifferentiated mesenchyme, and smooth muscle actin in mesenchyme and on smooth
      muscle "collars" around dilated tubules. In addition, some cases showed
      reexpression of vimentin and desmin on proximal tubular epithelial cells. Taken
      together, these findings provide a valuable database for tracking the expression
      of intermediate filaments throughout renal development in sheep and have further
      characterized the nature of the response to injury by the developing kidney, a
      response that is characterized by proliferation of mesenchyme and both
      reexpression and upregulation of intermediate filaments within renal cells. In
      addition, the study has confirmed that the changes in cloned lamb nephropathy are
      established by day 85 of development.

PMID- 15557221
TI  - Characterization of vascular endothelial growth factor (VEGF) in the uterine
      cervix over pregnancy: effects of denervation and implications for cervical
      ripening.
AB  - Bilateral neurectomy of the pelvic nerve (BLPN) that carries uterine cervix
      related sensory nerves induces dystocia, and administration of its vasoactive
      neuropeptides induces changes in the cervical microvasculature, resembling those
      that occur in the ripening cervix. This study was designed to test the hypothesis
      that (a) the cervix of pregnant rats expresses vascular endothelial growth factor
      (VEGF) and components of the angiogenic signaling pathway [VEGF receptors (Flt-1,
      KDR), activity of protein kinase B, Akt (phosphorylated Akt), and endothelial
      nitric oxide synthase (eNOS)] and von Willebrand Factor (vWF) and that these
      molecules undergo changes with pregnancy, and (b) bilateral pelvic neurectomy
      (BLPN) alters levels of VEGF concentration in the cervix. Using RT-PCR and
      sequencing, two VEGF isoforms, 120 and 164, were identified in the rat cervix.
      VEGF, VEGF receptor-1 (Flt-1), eNOS, and vWF immunoreactivities (ir) were
      localized in the microvasculature of cervical stroma. Their protein levels
      increased during pregnancy but decreased to control levels by 2 days postpartum.
      VEGF receptor-2 (KDR)-ir was confined to the epithelium of the endocervix. BLPN
      downregulated levels of VEGF by a third. Therefore, the components of the
      angiogenic signaling pathway are expressed in the cervix and change over
      pregnancy. Furthermore, angiogenic and sensory neuronal factors may be important
      in regulating the dynamic microvasculature in the ripening cervix and may
      subsequently play a role in cervical ripening and the birth process.

PMID- 15557222
TI  - Neutralizing human antibodies to varicella-zoster virus (VZV) derived from a VZV
      patient recombinant antibody library.
AB  - Varicella-zoster virus (VZV), the causative agent of chickenpox and herpes
      zoster, can be life-threatening in prematurely born children and in children with
      immune defects or who are under immunosuppressive treatment. Therefore agents for
      passive immunization, such as VZV-specific immunoglobulin preparations (VZIG)
      derived from convalescent plasma, are crucial in the prophylaxis of VZV
      infection. This study describes the isolation of human VZV-neutralizing
      recombinant antibodies. A human single-chain variable fragment (scFv) phage
      display library was generated from RNA extracted from peripheral blood
      lymphocytes of a convalescent varicella patient. Specific phage antibodies were
      selected against VZV-infected human fibroblasts, and eight unique clones were
      further expressed as soluble scFv in Escherichia coli. They all showed binding
      characteristics to varicella antigens with affinities in the K(D) range 0.1-0.2
      muM. Two of the scFv antibodies, VZV4 and VZV5, showed dose-dependent in vitro
      neutralization of VZV. VZV39 also showed a neutralizing effect as scFv, an effect
      that was increased 4000-fold by conversion into IgG and was further increased by
      the addition of complement. This is possibly the first time that monovalent scFv
      antibodies have been shown to neutralize VZV in vitro. This finding will have an
      impact on the production of new prophylactic antibodies, as such antibody
      fragments can be cost-effectively produced in E. coli. The antibodies isolated
      bind both complement-dependent and -independent epitopes for neutralization, thus
      they may prove useful tools for the study of VZV virulence mechanisms.

PMID- 15557223
TI  - Replication, recombination and packaging of amplicon DNA in cells infected with
      the herpes simplex virus type 1 alkaline nuclease null mutant ambUL12.
AB  - The alkaline nuclease (AN) encoded by gene UL12 of herpes simplex virus type 1
      (HSV-1) is essential for efficient virus replication but its role during the
      lytic cycle remains incompletely understood. Inactivation of the UL12 gene
      results in reductions in viral DNA synthesis, DNA packaging, egress of DNA
      containing capsids from the nucleus and ability of progeny virions to initiate
      new cycles of infection. Mechanistically, AN has been implicated in resolving
      branched structures in HSV-1 replicative intermediates prior to encapsidation,
      and promoting DNA strand-exchange. In this study, amplicons (bacterial plasmids
      containing functional copies of a virus replication origin and packaging signal)
      were used to analyse further the defects of the UL12 null mutant ambUL12. When
      ambUL12 was used as a helper virus both replication and packaging of the
      transfected amplicon were reduced in comparison with cells infected with wild
      type (wt) HSV-1, and to extents similar to those previously observed for genomic
      ambUL12 DNA. By using amplicons differing at a specific restriction endonuclease
      site it was demonstrated that replicating molecules exhibit high frequency
      intermolecular recombination in both wt- and mutant-infected cells. Surprisingly,
      in the absence of the UL12 product, amplicons lacking a functional encapsidation
      signal were packaged. Moreover, these packaged molecules could be serially
      propagated indicating that they had been incorporated into functional virions.
      This difference in packaging specificity between wt HSV-1 and ambUL12 might
      indicate that replicative intermediates accumulating in the absence of AN contain
      an increased incidence of structures that can serve for the initiation of DNA
      packaging.

PMID- 15557224
TI  - Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3
      when overexpressed in transfected cells.
AB  - Infection of cattle or bovine cells with bovine herpesvirus 1 (BHV-1) leads to
      increased apoptosis. Previous studies indicated that BHV-1 infected cell protein
      0 (bICP0), the major transcriptional regulatory protein of BHV-1, is toxic in
      transiently transfected cells. Point mutations within the zinc RING finger of
      bICP0 reduced toxicity and eliminated the ability of bICP0 to activate viral gene
      expression. In mouse neuroblastoma cells (neuro-2A) and bovine turbinate cells,
      bICP0 activated caspase 3, a key regulatory protein in the apoptotic pathway. A
      pro-apoptotic gene (Bax), but not bICP0, induced caspase 3 cleavage and
      activation by 8 h after transfection of neuro-2A cells. Conversely, bICP0 or the
      N-terminal 356 aa of bICP0 did not induce caspase 3 cleavage in neuro-2A cells
      until 30 h after transfection, suggesting that bICP0 stimulates caspase 3
      cleavage by an indirect mechanism. These studies indicate that the toxic
      functions of bICP0 correlate with caspase 3 cleavage and activation.

PMID- 15557225
TI  - Alphaherpesvirus glycoprotein M causes the relocalization of plasma membrane
      proteins.
AB  - Herpesvirus glycoprotein M (gM) is a multiple-spanning integral membrane protein
      found within the envelope of mature herpesviruses and is conserved throughout the
      Herpesviridae. gM is defined as a non-essential glycoprotein in
      alphaherpesviruses and has been proposed as playing a role in controlling final
      envelopment in a late secretory-pathway compartment such as the trans-Golgi
      network (TGN). Additionally, gM proteins have been shown to inhibit cell-cell
      fusion in transfection-based assays by an as yet unclear mechanism. Here, the
      effect of pseudorabies virus (PRV) gM and the herpes simplex virus type 1 (HSV-1)
      gM/UL49A complex on the fusion events caused by the HSV-1 glycoproteins gB, gD,
      gH and gL was investigated. Fusion of cells expressing HSV-1 gB, gD, gH and gL
      was efficiently inhibited by both PRV gM and HSV-1 gM/UL49A. Furthermore,
      expression of PRV gM or HSV-1 gM/UL49A, which are themselves localized to the
      TGN, caused both gD and gH/L to be relocalized from the plasma membrane to a
      juxtanuclear compartment, suggesting that fusion inhibition is caused by the
      removal of 'fusion' proteins from the cell surface. The ability of gM to cause
      the relocalization of plasma membrane proteins was not restricted to HSV-1
      glycoproteins, as other viral and non-viral proteins were also affected. These
      data suggest that herpesvirus gM (gM/N) can alter the membrane trafficking
      itineraries of a broad range of proteins and this may have multiple functions.

PMID- 15557226
TI  - Replication of varicella-zoster virus is influenced by the levels of JNK/SAPK and
      p38/MAPK activation.
AB  - Stimulation of the Jun NH(2)-terminal kinase/stress-activated protein kinase
      (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK) is part of the
      stress-related signal transduction pathways conveying signals from the cell
      surface into the nucleus in order to initiate programmes of gene expression.
      Here, it was shown that infection by varicella-zoster virus (VZV) caused a 34
      fold increase in activation of JNK/SAPK in the early phase of infection and a 2
      fold increase in activation of p38/MAPK in the later phase. The phosphorylation
      of downstream targets c-Jun and ATF-2 was also increased; subsequent cascades to
      induce pro-inflammatory responses were significantly activated whereas cascades
      to activate apoptotic events were not. In the late phase of infection, both
      JNK/SAPK and p38/MAPK activities were reduced to basal levels. The use of
      specific inhibitors demonstrated that inhibition of JNK/SAPK resulted in a 2-fold
      increase in VZV replication whereas a strong decrease in virus replication was
      observed after inhibition of p38/MAPK. In contrast, constitutive activation of
      JNK/SAPK resulted in a decline in VZV replication. Blocking gene expression by
      treating cells with actinomycin D or cycloheximide prior to infection resulted in
      activation of neither JNK/SAPK nor p38/MAPK. It was assumed that the presence of
      tegument proteins was not sufficient to activate stress pathways, but that
      expression of viral genes was necessary. This suggests that activation of stress
      pathways by VZV infection represents a finely regulated system that activates
      cellular transcription factors for transregulation of VZV-encoded genes, but
      prevents activation of cellular defence mechanisms.

PMID- 15557227
TI  - Alteration of cellular RNA splicing and polyadenylation machineries during
      productive human cytomegalovirus infection.
AB  - Alternative processing of human cytomegalovirus (HCMV) UL37 pre-mRNA
      predominantly produces the unspliced UL37 exon 1 (UL37x1) RNA and multiple, lower
      abundance, alternatively spliced UL37 RNAs. The relative abundance of UL37x1
      unspliced RNA is surprising because it requires the favoured use of a
      polyadenylation signal within UL37 intron 1, just upstream of the UL37 exon 2
      (UL37x2) acceptor. Here, it was shown that a downstream element (DSE) in UL37x2
      strongly enhanced processing at the UL37x1 polyadenylation site, but did not
      influence UL37x1-x2 splicing. There was a potential binding site (UCUU) for
      polypyrimidine tract-binding protein (PTB) at the UL37x1 polyadenylation/cleavage
      site and its mutation to UGGG reduced both polyadenylation and splicing of UL37x1
      x2 minigene pre-mRNA, suggesting a role in both RNA processing events. To
      determine whether lytic HCMV infection altered the balance of RNA processing
      factors, which bind to UL37 pre-mRNA cis elements, these were investigated in
      permissively infected primary and immortalized human diploid fibroblasts (HFFs)
      and epithelial cells. Induction of polyadenylation factors in HCMV-infected,
      serum-starved (G(0)) HFFs was also investigated. Permissive HCMV infection
      consistently increased, albeit with different kinetics, the abundance of cleavage
      stimulation factor 64 (CstF-64) and PTB, and altered hypo-phosphorylated SF2 in
      different cell types. Moreover, the preponderance of UL37x1 RNA increased during
      infection and correlated with CstF-64 induction, whereas the complexity of the
      lower abundance UL37 spliced RNAs transiently increased following reduction of
      hypo-phosphorylated SF2. Collectively, multiple UL37 RNA polyadenylation cis
      elements and induced cellular factors in HCMV-infected cells strongly favoured
      the production of UL37x1 unspliced RNA.

PMID- 15557228
TI  - Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected
      fibroblasts against virus-induced apoptosis and are required for efficient virus
      replication.
AB  - Human cytomegalovirus (HCMV) strain AD169 mutants carrying transposon insertions
      or large deletions in UL37 exon 1 (UL37x1) were recovered from modified bacterial
      artificial chromosomes by reconstitution in human fibroblasts expressing the
      adenovirus anti-apoptotic protein E1B19K. UL37x1 mutant growth was severely
      compromised in normal fibroblasts, with minimal release of infectious progeny.
      Growth in E1B19K-expressing cells was restored, but did not reach wild-type
      levels. Normal fibroblasts infected by UL37x1 mutants underwent apoptosis
      spontaneously between 48 and 96 h after infection. Apoptosis was inhibited by
      treatment of cells with the broad-spectrum caspase inhibitor z-Val-Ala-Asp(OMe)
      fluoromethylketone, resulting in substantially increased release of virus.
      Inhibition of viral DNA replication by phosphonoformate or ganciclovir also
      inhibited apoptosis, implying that death was triggered by late viral functions or
      by replication and packaging of the viral genome. Immunofluorescent staining
      showed that although viral proteins accumulated normally during delayed-early
      phase and viral DNA replication compartments formed, viral late proteins were
      detected only rarely, suggesting that spontaneous apoptosis occurs early in late
      phase. These results demonstrate that anti-apoptotic proteins encoded by HCMV
      UL37x1 [pUL37x1 (vMIA), gpUL37 and gpUL37(M)] prevent apoptosis that would
      otherwise be initiated by the replication programme of the virus and are required
      for efficient and sustainable virus replication.

PMID- 15557229
TI  - Choristoneura fumiferana nucleopolyhedrovirus encodes a functional 3'-5'
      exonuclease.
AB  - The Choristoneura fumiferana nucleopolyhedrovirus (CfMNPV) encodes an ORF
      homologous to type III 3'-5' exonucleases. The CfMNPV v-trex ORF was cloned into
      the Bac-to-Bac baculovirus expression-vector system, expressed in insect Sf21
      cells with an N-terminal His tag and purified to homogeneity by using Ni-NTA
      affinity chromatography. Biochemical characterization of the purified V-TREX
      confirmed that this viral protein is a functional 3'-5' exonuclease that cleaves
      oligonucleotides from the 3' end in a stepwise, distributive manner, suggesting a
      role in proofreading during viral DNA replication and DNA repair. Enhanced
      degradation of a 5'-digoxigenin- or 5'-(32)P-labelled oligo(dT)(30) substrate was
      observed at increasing incubation times or increased amounts of V-TREX. The 3'
      excision activity of V-TREX was maximal at alkaline pH (9.5) in the presence of 5
      mM MgCl(2), 2 mM dithiothreitol and 0.1 mg BSA ml(-1).

PMID- 15557230
TI  - Analysis of baculovirus IE1 in living cells: dynamics and spatial relationships
      to viral structural proteins.
AB  - IE1, a principal transcriptional activator of the baculovirus Bombyx mori
      nucleopolyhedrovirus (BmNPV), is an essential factor for viral DNA replication.
      During viral infection, IE1 accumulates in discrete subnuclear structures where
      viral DNA replication occurs. To analyse the dynamic properties of IE1, we
      monitored green fluorescent protein-tagged IE1 (IE1-GFP) in BmNPV-infected B.
      mori cells by live-cell microscopy. Time-lapse imaging showed that IE1-associated
      structures gradually expanded and occasionally fused with one another, while
      photobleaching experiments revealed that IE1-GFP was relatively immobile inside
      the IE1-associated structures. To investigate the spatial relationships between
      IE1 and viral structural proteins in infected cells, three GFP-tagged viral
      components were expressed together with DsRed-tagged IE1. Two structural proteins
      that constitute the occlusion-derived virus (ODV), P91-GFP and GFP-ODV-E25,
      localized to the periphery of the IE1-associated structures. While local
      accumulations of these proteins were often in contact with the IE1-associated
      structures, they did not extend beyond the boundaries of the structures. In
      contrast, the major capsid protein VP39-GFP predominantly accumulated within the
      IE1-associated structures. These data indicated, in conjunction with the finding
      of a high DNA content in the structures, that IE1 localizes to the virogenic
      stroma and therefore support the prediction previously proposed that the
      virogenic stroma is a site for viral DNA replication as well as for the assembly
      of nucleocapsids.

PMID- 15557231
TI  - Cyclin A expression and growth in suspension can be uncoupled from p27
      deregulation and extracellular signal-regulated kinase activity in cells
      transformed by bovine papillomavirus type 4 E5.
AB  - As the biochemical detection of bovine papillomavirus type 4 E5 is problematic, a
      fusion form of E5 and the green fluorescent protein (GFP-E5) was constructed and
      its characteristics were examined. GFP-E5 was detected in cells by
      autofluorescence and immunoblotting. Like wild-type (wt) E5, GFP-E5 localized in
      the endomembranes and permitted anchorage-independent (AI) growth. However,
      unlike wt E5, cells expressing GFP-E5 became quiescent in low serum and failed to
      sustain expression of cyclins D1 and to inactivate retinoblastoma protein (pRb).
      The normal anchorage requirement for cyclin D1 and cyclin A expression was
      abolished in cells expressing wt E5 or GFP-E5, residual extracellular signal
      regulated kinase (ERK 1/2) activity was not required to sustain cyclin D1 and
      cyclin A expression in suspension and deregulation of cyclin A-cyclin-dependent
      kinase (CDK) activity was sufficient to account for AI growth of cells expressing
      E5. Constitutive upregulation of the CDK inhibitor p27(KIP1), characteristic of
      cells expressing wt E5, was not observed in those expressing GFP-E5; therefore,
      p27(KIP1) deregulation is not required for E5-mediated AI growth.

PMID- 15557232
TI  - Tumorigenic poxviruses: growth factors in a viral context?
AB  - Shope fibroma virus (SFV) is one of the few poxviruses that induce cutaneous
      tumours, whereas myxoma virus, a closely related leporipoxvirus, does not.
      However, both have a virally encoded homologue of the epidermal growth factor
      (namely SFGF and MGF, respectively) that is considered to be crucial for poxvirus
      tumorigenesis. In this study, the role of viral growth factors in the context of
      infection with SFV, a tumorigenic leporipoxvirus, was investigated. An SFV mutant
      was engineered with the sfgf gene deleted and replaced with mgf. Macroscopic,
      histological and cytological examinations led to the conclusion that growth
      factors are indeed important for the development and maintenance of fibromas,
      provided that they are expressed in the proper viral context. However, they are
      not exchangeable and MGF cannot substitute for SFGF in the genesis of fibromas.
      It is likely that factors other than viral epidermal growth factor homologues
      influence the development of tumours.

PMID- 15557233
TI  - Molecular epidemiology of white spot syndrome virus within Vietnam.
AB  - White spot syndrome virus (WSSV), the sole member of the virus family
      Nimaviridae, is a large double-stranded DNA virus that infects shrimp and other
      crustaceans. By alignment of three completely sequenced isolates originating from
      Taiwan (WSSV-TW), China (WSSV-CN) and Thailand (WSSV-TH), the variable loci in
      the genome were mapped. The variation suggests the spread of WSSV from a common
      ancestor originating from either side of the Taiwan Strait to Thailand, but
      support for this hypothesis through analysis of geographical intermediates is
      sought. RFLP analysis of eight Vietnamese WSSV isolates, of which six were
      collected along the central coast (VN-central) and two along the south coast (VN
      south), showed apparent sequence variation in the variable loci identified
      previously. These loci were characterized in detail by PCR amplification, cloning
      and sequencing. Relative to WSSV-TW, all VN-central isolates showed a
      approximately 8.5 kb deletion in the major variable region ORF23/24, whereas the
      VN-south isolates contain a deletion of approximately 11.5 or approximately 12.2
      kb, compared to a approximately 1.2 or approximately 13.2 kb deletion in WSSV-CN
      and WSSV-TH, respectively. The minor variable region ORF14/15 showed deletions of
      various sizes compared with WSSV-TH for all eight VN isolates. The data suggest
      that the VN isolates and WSSV-TH have a common lineage, which branched off from
      WSSV-TW and WSSV-CN early on, and that WSSV entered Vietnam by multiple
      introductions. A model is presented for the spread of WSSV from either side of
      the Taiwan Strait into Vietnam based on the gradually increasing deletions of
      both 'variable regions'. The number and order of repeat units within ORF75 and
      ORF125 appeared to be suitable markers to study regional spread of WSSV.

PMID- 15557234
TI  - Hepatitis C virus population analysis of a single-source nosocomial outbreak
      reveals an inverse correlation between viral load and quasispecies complexity.
AB  - The features of Hepatitis C virus (HCV) quasispecies within an envelope segment
      including the hypervariable region 1 were analysed at an early time point post
      infection in seven patients that acquired HCV from a single common donor during a
      nosocomial outbreak. The grouping of patients according to viral load was
      reflected in the structure of the quasispecies. A higher viral load correlated
      with the presence of a predominant HCV genome and a corresponding lower
      quasispecies complexity. The quasispecies complexity itself was not correlated
      with HCV clearance or persistence. Thus, the relationship between an intrapatient
      HCV quasispecies and the clinical outcome of an HCV infection is more complex
      than previously anticipated.

PMID- 15557235
TI  - Histidine 39 in the dengue virus type 2 M protein has an important role in virus
      assembly.
AB  - The mature flavivirus particle comprises a nucleocapsid core surrounded by a
      lipid bilayer containing the membrane (M) (derived from the precursor prM) and
      envelope (E) proteins. The formation of intracellular prM/E heterodimers occurs
      rapidly after translation and is believed to be important for the assembly and
      secretion of immature virus particles. In this study, the role of the His residue
      at position 39 in the M protein (M39) of dengue virus type 2 (DENV-2) in the
      virus life cycle was investigated. Mutations encoding basic (Arg), non-polar (Leu
      and Pro) and uncharged polar (Asn, Gln and Tyr) amino acids at M39 were
      introduced into a DENV-2 genomic-length cDNA clone and their effects on virus
      replication were examined. Substitution of the His residue with non-polar amino
      acids abolished virus replication, whereas substitution with basic or uncharged
      polar amino acids decreased virus replication moderately ( approximately 2
      log(10) p.f.u. ml(-1) decrease in viral titre for Arg and Asn) or severely (>3.5
      log(10) p.f.u. ml(-1) decrease in viral titre for Gln and Tyr). Selected
      mutations were introduced into a prM-E gene cassette and expressed transiently in
      COS cells to investigate whether the mutations impaired prM/E association or
      secretion. None of the mutations was found to disrupt the formation of
      intracellular prM/E heterodimers. However, the mutations that abolished virus
      replication prevented secretion of prM/E complexes. The results of this study
      pinpoint a critical residue in the M protein that potentially plays a role in
      viral morphogenesis, secretion and entry.

PMID- 15557236
TI  - Viral envelope protein glycosylation is a molecular determinant of the
      neuroinvasiveness of the New York strain of West Nile virus.
AB  - Two New York (NY) strains of the West Nile (WN) virus were plaque-purified and
      four variants that had different amino acid sequences at the N-linked
      glycosylation site in the envelope (E) protein sequence were isolated. The E
      protein was glycosylated in only two of these strain variants. To determine the
      relationship between E protein glycosylation and pathogenicity of the WN virus, 6
      week-old mice were infected subcutaneously with these variants. Mice infected
      with viruses that carried the glycosylated E protein developed lethal infection,
      whereas mice infected with viruses that carried the non-glycosylated E protein
      showed low mortality. In contrast, intracerebral infection of mice with viruses
      carrying either the glycosylated or non-glycosylated forms of the E protein
      resulted in lethal infection. These results suggested that E protein
      glycosylation is a molecular determinant of neuroinvasiveness in the NY strains
      of WN virus.

PMID- 15557237
TI  - Genetic and antigenic characterization of an atypical pestivirus isolate, a
      putative member of a novel pestivirus species.
AB  - The genus Pestivirus within the family Flaviviridae currently consists of four
      different main species: Classical swine fever virus, Bovine viral diarrhea virus
      types 1 and 2 and Border disease virus. A fifth tentative species is represented
      by an isolate from a giraffe. In this study, a completely new pestivirus,
      isolated from a batch of fetal calf serum that was collected in Brazil, is
      described. It is proposed that the isolate D32/00_'HoBi' may constitute a novel
      sixth pestivirus species, because it is genetically, as well as antigenically,
      markedly different from all other pestiviruses. Based on the entire N(pro)- and
      E2-encoding sequences, identities of <70 % to all other pestivirus species were
      determined. Similarly, cross-neutralization and binding studies using antisera
      and mAbs revealed marked antigenic differences between D32/00_'HoBi' and all
      other pestiviruses.

PMID- 15557238
TI  - A novel pestivirus associated with deaths in Pyrenean chamois (Rupicapra
      pyrenaica pyrenaica).
AB  - During investigations into recent population decreases in Pyrenean chamois
      (Rupicapra pyrenaica pyrenaica) 21 animals found dead or dying were necropsied.
      Immunohistochemistry revealed the presence of a pestivirus in organs from two of
      the 21 chamois. From one of these animals a pestivirus was isolated from the
      spleen, skin and serum. The virus had better growth in ovine than in bovine cells
      and was neutralized most effectively by an anti-border disease virus (BDV)
      reference antiserum. Using panpestivirus and genotype-specific primers selected
      from 5'-untranslated region (UTR) of the pestivirus genome, BDV RNA was
      demonstrated by RT-PCR. Comparison of the chamois sequences from 5'-UTR, entire
      N(pro) and E2 gene coding regions with those of other pestivirus genotypes
      revealed that this virus did not fall into any of the pestivirus genotypes
      identified so far. Results of phylogenetic analysis suggested that the chamois
      pestivirus was closely related to BDV and it was typed as BDV-4 genotype.

PMID- 15557239
TI  - Effect of the 5' non-translated region on self-assembly of hepatitis C virus
      genotype 1a structural proteins produced in insect cells.
AB  - The effect of the 5' non-translated region (5'NTR) on hepatitis C virus (HCV)
      morphogenesis in insect cells is investigated in this study. Expression in
      baculovirus-infected cells of a sequence encoding the C and E1 structural
      proteins under the control of the very late promoter P10 (AcSLP10-C-E1) led to
      the synthesis of C and C-E1 complexes, essentially found in dense reticular
      material associated with the ER and sedimenting at a density of 1.24-1.26 g ml(
      1). Addition of the 5'NTR upstream of the C-E1 sequence (AcSLP10-5'NTR-E1)
      prevents translation from the initiating codon, probably because of the presence
      of five AUG codons in this sequence. When cells were co-infected with these two
      viruses, virus-like particles (VLPs) were found in the cytoplasm. The size and
      shape of these VLPs were variable. Concomitantly, a shift in the sedimentation
      profile from 1.24-1.26 to 1.15-1.18 g ml(-1) was observed, suggesting an
      association of C/E1 with the ER membrane. A unique vector was then constructed
      bearing a mutated 5'NTR (mutation of the five AUGs) and the sequence encoding all
      of the structural proteins and part of NS2 (5'NTRm-C-E1-E2-p7-NS2Delta).
      Translation of structural proteins was restored and electron microscopic
      observation of a cytoplasmic extract showed the presence of icosahedral particles
      with a density of 1.15-1.18 g ml(-1).

PMID- 15557240
TI  - Complete sequence of the G glycoprotein gene of avian metapneumovirus subgroup C
      and identification of a divergent domain in the predicted protein.
AB  - The complete nucleotide sequences of the attachment glycoprotein (G) genes of
      three strains of avian metapneumovirus subgroup C (AMPV-C) were determined from
      the viral genomic and mRNAs. The G gene of AMPV-C was 1798 nt (1015 nt longer
      than previously reported) and the derived polypeptide had 585 aa. The deduced
      amino acid sequence of the predicted G protein of AMPV-C strain Colorado (AMPV
      CO) showed 21-25 % amino acid identity to the G proteins of human
      metapneumoviruses, but only 14-16 % amino acid identity to those of other AMPV
      subgroups. The predicted G protein of AMPV-CO showed 98 and 81 % amino acid
      identity to those of AMPV-C strains Mn-1a and Mn-2a, respectively, indicating
      considerable sequence variation in the G proteins of AMPV-C isolates. Comparison
      of the G protein sequences of AMPV-CO and Mn-2a identified a highly divergent
      domain (48 % amino acid identity) at aa 300-450.

PMID- 15557241
TI  - Thermostability of the human respiratory syncytial virus fusion protein before
      and after activation: implications for the membrane-fusion mechanism.
AB  - Anchorless fusion (F) proteins () of human respiratory syncytial virus (RSV) are
      seen by electron microscopy as unaggregated cones when the proteolytic cleavage
      at two furin sites required for membrane-fusion activity is incomplete, but
      aggregate into rosettes of lollipop-shaped spikes following cleavage. To show
      that this aggregation occurred by interactions of the fusion peptide, a deletion
      mutant of lacking the first half of the fusion peptide was generated. This mutant
      remained unaggregated even after completion of cleavage, supporting the notion
      that aggregation of involved the fusion peptide. As exposure of the fusion
      peptide is a key event that occurs after activation of F proteins, the uncleaved
      and cleaved forms of may represent the pre- and post-active forms of RSV F
      protein. In an analysis of the structural differences between the two forms,
      their thermostability before and after proteolytic cleavage was examined. In
      contrast to other viral proteins involved in membrane fusion (e.g. influenza
      haemagglutinin), the pre-active (uncleaved) and post-active (cleaved) forms of
      were equally resistant to heat denaturation, assessed by spectrofluorimetry,
      circular dichroism or antibody binding. These results are interpreted in terms of
      the proposed structural changes associated with the process of membrane fusion
      mediated by RSV F protein.

PMID- 15557242
TI  - Increased amounts of the influenza virus nucleoprotein do not promote higher
      levels of viral genome replication.
AB  - Influenza virus genome replication requires the virus-encoded nucleoprotein (NP),
      partly because it is necessary to encapsidate the viral genomic RNA (vRNA) and
      antigenomic cRNA segments into ribonucleoproteins (RNPs). However, there is also
      evidence that NP actively regulates viral RNA synthesis and there is a long
      standing hypothesis that increased concentrations of NP in the cell are
      responsible for a switch from genome transcription to replication. Here, this
      hypothesis is tested in a recombinant setting and in the context of virus
      infection. In a plasmid-based system for reconstituting active viral RNPs in
      cells, titration of increasing amounts of NP did not promote higher levels of
      genome replication relative to transcription, but in fact caused the opposite
      effect. An approximately fourfold reduction in the ratio of genomic and
      antigenomic RNAs to mRNA was seen across an 80-fold range of NP plasmid
      concentrations. When cells were transfected with the same amounts of NP plasmid
      to establish a concentration gradient of NP prior to virus superinfection, no
      change in the ratio of cRNA to mRNA was seen for segments 5 and 7, or for the
      ratio of segment 5 vRNA to mRNA. A slight reduction in the ratio of segment 7
      vRNA to mRNA was seen. These findings do not support the simple hypothesis that
      increased intracellular concentrations of NP promote influenza virus genome
      replication.

PMID- 15557243
TI  - Functional comparison of the two gene products of Thogoto virus segment 6.
AB  - The sixth genomic segment of Thogoto virus (THOV) encodes two proteins, the viral
      matrix protein (M) and an accessory protein with an interferon (IFN)-antagonistic
      function named ML. M and ML are shown in this study to be structural components
      of the virion. Using an in vivo system based on the reconstitution of functional
      THOV ribonucleoprotein complexes from cloned cDNAs, it was demonstrated that M
      has an inhibitory effect on the viral RNA-dependent RNA polymerase (RdRP) and is
      essential for the formation of virus-like particles (VLPs). The functional domain
      responsible for the regulation of RdRP activity resides within the C-terminal
      half of M, while full-length M protein is required for VLP formation. The ML
      protein cannot complement M with respect to either RdRP downregulation or
      particle formation, although it is identical to M apart from a 38 aa extension at
      the C terminus. In contrast, ML, but not M, is able to prevent the induction of
      IFN-beta by double-stranded RNA. This function is contained within the C-terminal
      half of ML. These data suggest major structural differences between M and ML that
      could explain the different activities of the two proteins.

PMID- 15557244
TI  - Rescue of disabled infectious single-cycle (DISC) equine arteritis virus by using
      complementing cell lines that express minor structural glycoproteins.
AB  - Equine arteritis virus (EAV) contains seven structural proteins that are all
      required to produce infectious progeny. Alphavirus-based expression vectors have
      been generated for each of these proteins to explore the possibilities for their
      constitutive expression in cell lines. This approach was successful for minor
      glycoproteins GP(2b), GP(3) and GP(4) and for the E protein. Subsequently, it was
      demonstrated that cell lines expressing these proteins could rescue EAV mutants
      that were disabled in the expression of the corresponding gene, resulting in the
      production of virus particles carrying the mutant genome. This system was
      particularly efficient for GP(2b)- and GP(4)-knockout mutants. Upon infection of
      non-complementing cells with these mutants, a self-limiting single cycle of
      replication was initiated, resulting in the expression of all but one of the
      viral proteins. These disabled infectious single-cycle (DISC) arteriviruses can
      also be used to express foreign sequences and are potentially useful in both
      fundamental research and vaccine development.

PMID- 15557245
TI  - Significance of the oligosaccharides of the porcine reproductive and respiratory
      syndrome virus glycoproteins GP2a and GP5 for infectious virus production.
AB  - The arterivirus porcine reproductive and respiratory syndrome virus (PRRSV)
      contains four glycoproteins, GP(2a), GP(3), GP(4) and GP(5), the functions of
      which are still largely unresolved. In this study, the significance of the N
      glycosylation of the GP(2a) and GP(5) proteins of PRRSV strain LV was
      investigated. Both glycoproteins contain two predicted N-glycosylation sites that
      are highly conserved between North American-type and European-type PRRSV. Using
      site-directed mutagenesis, single and double mutant full-length PRRSV cDNA clones
      were generated. After analysing the expression of the mutant proteins and the
      actual use of the four putative glycosylation sites in the wild-type proteins,
      the production of mutant virus particles and their infectivities were
      investigated. The results showed that the N-linked glycans normally present on
      the GP(2a) protein are not essential for particle formation, as is the
      oligosaccharide attached to N53 of the GP(5) protein. In contrast, the
      oligosaccharide linked to N46 of the GP(5) protein is strongly required for virus
      particle production. The specific infectivities of the mutant viruses were
      investigated by comparing their infectivity-per-particle ratios with that of wild
      type virus. The results showed that the lack of either one or both of the N
      linked oligosaccharides on GP(2a) or of the oligosaccharide attached to N53 of
      GP(5) did not significantly affect the infectivities of the viruses. In contrast,
      the two recombinant viruses lacking the oligosaccharide bound to N46 exhibited a
      significantly reduced specific infectivity compared with the wild-type virus. The
      implications of the differential requirements of the modifications of GP(2a) and
      GP(5) for PRRSV assembly and infectivity are discussed.

PMID- 15557246
TI  - Interactions amongst rabies virus nucleoprotein, phosphoprotein and genomic RNA
      in virus-infected and transfected cells.
AB  - Previous in vitro studies have indicated that rabies virus (RV) phosphoprotein
      (P), by interacting with the nucleoprotein (N), confers the specificity of
      genomic RNA encapsidation by N. In this study, interactions amongst N, P and the
      genomic RNA in virus-infected as well as in transfected cells were studied. The
      results showed that when N was expressed alone, it bound non-specific RNA,
      particularly the N mRNA. When N and P were co-expressed, they formed N-P
      complexes that did not bind to non-specific RNA. When N and P were co-expressed
      together with (mini-)genomic RNA, N-P complexes preferentially bound the (mini
      )genomic RNA. This demonstrated that RV P, by binding to N, does indeed confer
      specificity of genomic RNA encapsidation by N in vivo. Furthermore, the role of N
      phosphorylation in the N, P and RNA interactions was investigated. It was found
      that only N that bound to RNA was phosphorylated, while N in the N-P complex
      prior to RNA encapsidation was not, suggesting that RV P, by binding to nascent
      N, prevents the immediate phosphorylation of de novo-synthesized N. However,
      mutation at the phosphorylation site of N did not alter the pattern of N-P and N
      RNA interactions, indicating that N phosphorylation per se does not play a direct
      role in N-P interaction and RNA encapsidation.

PMID- 15557247
TI  - Readily acquired secondary infections of human and simian immunodeficiency
      viruses following single intravenous exposure in non-human primates.
AB  - Accumulating evidence suggests that exposed individuals may acquire multiple
      human immunodeficiency virus (HIV) infections more frequently than originally
      believed. As a result, circulating recombinant forms of HIV are emerging that are
      of particular concern in the AIDS epidemic and HIV vaccine development efforts.
      The aim of this study was to determine under what conditions secondary or
      superinfections of HIV or simian immunodeficiency virus (SIV) may be acquired
      under controlled settings in well-defined, non-human primate models.
      Retrospective analysis of macaques that had acquired apparent immunity upon
      infection with a defined attenuated SIV(mac) strain revealed that eight out of
      eight animals that were secondarily exposed to a new virus variant became
      infected with the new virus strain, but at low levels. Interestingly, similarly
      high frequencies of secondary infections were observed after early (4 months), as
      well as late (5 years), exposure following primary infection. As possible causes
      of susceptibility to secondary infections, perturbations in the immune system
      associated with exacerbated infections were then investigated prospectively.
      Results revealed that short-term immune-suppression therapy did not increase
      susceptibility to secondary infections. Taken together, data suggested that
      neither early- nor late-exposure immune-suppressive events following primary
      infection accounted for the observed high incidence of secondary infections. With
      HIV-1, the question of whether secondary infections with very closely related
      viral variants could occur in the chimpanzee model was addressed. In both animal
      models, secondary infections were confirmed, notably with relatively closely
      related SIV(mac) or HIV-1 strains, following a single exposure to the secondary
      virus strain. These findings reveal that secondary lentiviral infections may be
      acquired readily during different stages of primary infection, in contrast to co
      infections, which are acquired at the moment of initial infection.

PMID- 15557248
TI  - Complete sequence of a picorna-like virus of the genus Iflavirus replicating in
      the mite Varroa destructor.
AB  - Aggregations of 27 nm virus-like particles were observed in electron microscopy
      images of sectioned Varroa destructor mite tissue. The scattered occurrence of
      individual particles and accumulation of the virions in lattices in the cytoplasm
      gave an apparent indication that the virus replicates in the mite. Sequence
      analysis of the RNA of the purified virus revealed a genome organization with
      high similarity to that of members of the genus Iflavirus. Phylogenetic analysis
      of the polymerase showed that the virus was related most closely to Deformed wing
      virus (DWV) and Kakugo virus (KV) of bees. The virus has a genome of 10 112 nt
      without the poly(A) tail, with an overall RNA genome identity of 84 % to those of
      DWV and KV and has one large ORF, translated into a 2893 aa polyprotein with an
      amino acid identity of 95 % to those of DWV and KV. The first 1455 nt of the ORF
      encoding the lower molecular mass structural proteins shows the greatest
      diversion from those of DWV and KV, with an RNA identity of 79 %, and translates
      to a polypeptide of 485 aa with an identity of 90 %. The name proposed for this
      virus is Varroa destructor virus 1 (VDV-1). To determine whether VDV-1 replicates
      in mites, a selective RT-PCR was done to detect the presence of the negative
      sense RNA strand. The virus isolate and the closely related DWV could be
      discriminated by two primer sets, each specific to one virus. Both viruses
      replicated in the population of the mite species studied.

PMID- 15557249
TI  - Host-specific encapsidation of a defective RNA 3 of Cucumber mosaic virus.
AB  - Defective (D) RNAs were generated in tobacco upon passage of two isolates of
      Cucumber mosaic virus (CMV) initially derived from RNA transcripts of cDNA
      clones. In both cases, the D RNA was derived by a single in-frame deletion of
      either 339 or 411 nt within the 3a gene of Fny-CMV RNA 3 or M-CMV RNA 3,
      respectively. The generation of D RNAs was rare and occurred with two CMV
      isolates, the virions of which were known to differ in physico-chemical
      properties. The Fny-CMV D RNA 3, designated D RNA 3-1, was maintained by passage
      together with Fny-CMV in tobacco, but was lost by passage in squash. D RNA 3-1
      accumulated in the inoculated squash cotyledons but not in upper, systemically
      infected leaves. Virions purified from infected squash cotyledons or leaf
      mesophyll protoplasts did not contain D RNA 3-1. Therefore, the failure of D RNA
      3-1 to accumulate in squash leaves systemically infected by CMV was due to a lack
      of encapsidation of the D RNA 3-1 and movement out of the inoculated leaves.

PMID- 15557250
TI  - P6 protein of Cauliflower mosaic virus, a translation reinitiator, interacts with
      ribosomal protein L13 from Arabidopsis thaliana.
AB  - The P6 protein of Cauliflower mosaic virus (CaMV) transactivates translation of
      the CaMV 35S polycistronic pregenomic RNA and its spliced versions, and thus
      allows synthesis of a complete set of viral proteins. Previous studies have shown
      that P6 interacts with plant L18 and L24 ribosomal proteins and initiation factor
      eIF3, and it has been proposed that these interactions are involved in the
      reinitiation of translation of polycistronic viral RNAs. This study characterizes
      a novel cellular partner of P6, the ribosomal protein L13 from Arabidopsis
      thaliana. Far-Western assays performed with several P6 deletion mutants have
      shown that L13 interacts with the miniTAV of P6, which represents the minimal
      domain for transactivation, suggesting that the P6-L13 interaction might also be
      involved in this process. L13 and L18 were found to bind to the same region
      within the miniTAV. Competition assays between L18 and L13 for binding to miniTAV
      suggest that interactions between P6 and these ribosomal proteins involve
      separate P6 molecules, and/or occur at different stages of translation or in the
      context of another function also mediated by P6.

PMID- 15557251
TI  - High-level expression of alternative oxidase protein sequences enhances the
      spread of viral vectors in resistant and susceptible plants.
AB  - The alternative oxidase (AOX) is the terminal oxidase of the cyanide-resistant
      alternative respiratory pathway in plants and has been implicated in resistance
      to viruses. When tobacco mosaic virus (TMV) vectors were used to drive very high
      levels of expression of either AOX or AOX mutated in its active site (AOX-E),
      virus spread was enhanced. This was visualized as the induction of larger
      hypersensitive-response lesions after inoculation onto NN-genotype tobacco than
      those produced by vectors bearing sequences of comparable length [the green
      fluorescent protein (gfp) gene sequence or antisense aox] or the 'empty' viral
      vector. Also, in the highly susceptible host Nicotiana benthamiana, systemic
      movement of TMV vectors expressing AOX or AOX-E was faster than that of TMV
      constructs bearing gfp or antisense aox sequences. Notably, in N. benthamiana,
      TMV.AOX and TMV.AOX-E induced symptoms that were severe and ultimately included
      cell death, whereas the empty vector, TMV.GFP and the TMV vector expressing
      antisense aox sequences never induced necrosis. The results show that, if
      expressed at sufficiently high levels, active and inactive AOX proteins can
      affect virus spread and symptomology in plants.

PMID- 15557252
TI  - Studies on the origin and structure of tubules made by the movement protein of
      Cowpea mosaic virus.
AB  - Cowpea mosaic virus (CPMV) moves from cell to cell by transporting virus
      particles via tubules formed through plasmodesmata by the movement protein (MP).
      On the surface of protoplasts, a fusion between the MP and the green fluorescent
      protein forms similar tubules and peripheral punctate spots. Here it was shown by
      time-lapse microscopy that tubules can grow out from a subset of these peripheral
      punctate spots, which are dynamic structures that seem anchored to the plasma
      membrane. Fluorescence resonance energy transfer experiments showed that MP
      subunits interacted within the tubule, where they were virtually immobile,
      confirming that tubules consist of a highly organized MP multimer. Fluorescence
      recovery after photobleaching experiments with protoplasts, transiently
      expressing fluorescent plasma membrane-associated proteins of different sizes,
      indicated that tubules made by CPMV MP do not interact directly with the
      surrounding plasma membrane. These experiments indicated an indirect interaction
      between the tubule and the surrounding plasma membrane, possibly via a host
      plasma membrane protein.

PMID- 15557253
TI  - Role of glycosylphosphatidylinositols in the activation of phospholipase A2 and
      the neurotoxicity of prions.
AB  - Prion-induced neuronal injury in vivo is associated with prostaglandin E(2)
      production, a process that can be reproduced in tissue-culture models of prion
      disease. In the present study, neuronal phospholipase A(2) was activated by
      glycosylphosphatidylinositols (GPIs) isolated from the cellular prion protein
      (PrP(c)) or from disease-associated isoforms (PrP(Sc)), resulting in
      prostaglandin E(2) production, but not by GPIs isolated from Thy-1. The ability
      of GPIs to activate neuronal phospholipase A(2) was lost following the removal of
      acyl chains or cleavage of the phosphatidylinositol-glycan linkage, and was
      inhibited by a mAb that recognized phosphatidylinositol. In competition assays,
      pretreatment of neurons with partial GPIs, inositol monophosphate or sialic acid
      reduced the production of prostaglandin E(2) in response to a synthetic miniprion
      (sPrP106), a synthetic correlate of a PrP(Sc) species found in Gerstmann
      Straussler-Scheinker disease (HuPrP82-146), prion preparations or high
      concentrations of PrP-GPIs. In addition, neurons treated with inositol
      monophosphate or sialic acid were resistant to the otherwise toxic effects of
      sPrP106, HuPrP82-146 or prion preparations. This protective effect was selective,
      as inositol monophosphate- or sialic acid-treated neurons remained susceptible to
      the toxicity of arachidonic acid or platelet-activating factor. Addition of PrP
      GPIs to cortical neuronal cultures increased caspase-3 activity, a marker of
      apoptosis that is elevated in prion diseases. In contrast, treatment of such
      cultures with inositol monophosphate or sialic acid greatly reduced sPrP106
      induced caspase-3 activity and, in co-cultures, reduced the killing of sPrP106
      treated neurons by microglia. These results implicate phospholipase A(2)
      activation by PrP-GPIs as an early event in prion-induced neurodegeneration.

PMID- 15557254
TI  - Decontamination of surgical instruments from prion proteins: in vitro studies on
      the detachment, destabilization and degradation of PrPSc bound to steel surfaces.
AB  - Effective reprocessing of surgical instruments ensuring elimination of
      inadvertent contamination with infectious agents causing transmissible spongiform
      encephalopathies (TSEs) is essential for the prevention of iatrogenic
      transmission of Creutzfeldt-Jakob disease (CJD) or its new variant (vCJD) from
      asymptomatic carriers. In a search for effective yet instrument-friendly and
      routinely applicable reprocessing procedures, we used an in vitro carrier assay
      to assess the decontamination activity exerted by different reagents on
      pathological prion protein (PrP(Sc)), the biochemical marker for TSE infectivity,
      attached to steel surfaces. In this assay, steel wires were contaminated with
      263K scrapie brain homogenate and reprocessed for decontamination by exposure to
      several different test reagents. Residual contamination with PrP(Sc) and its
      protease-resistant core PrP27-30, still present after reprocessing on the wire
      surface or in the cleaning solution, was monitored by sensitive Western blot
      detection without or after proteinase K digestion. Using this approach, various
      reagents and processing conditions were screened for both their efficacy of
      decontamination and their active principles, such as detachment, destabilization
      or degradation of surface-bound prion protein. This revealed that, under
      appropriate conditions, relatively mild reagents such as 0.2 % SDS/0.3 % NaOH (pH
      12.8), a commercially available alkaline cleaner (pH 11.9-12.2), a disinfectant
      containing 0.2 % peracetic acid and low concentrations of NaOH (pH 8.9) or 5 %
      SDS (pH 7.1) exert potent decontaminating activities on PrP(Sc)/PrP27-30 attached
      to steel surfaces. For in vivo validation, wires reprocessed in these reagents
      have been implanted into reporter animals in ongoing experiments.

PMID- 15557256
TI  - Specificity in lipases: a computational study of transesterification of sucrose.
AB  - Computational conformational searches of putative transition states of the
      reaction of sucrose with vinyl laurate catalyzed by lipases from Candida
      antarctica B and Thermomyces lanuginosus have been carried out. The dielectric of
      the media have been varied to understand the role of protein plasticity in
      modulating the observed regioselective transesterification. The binding pocket of
      lipase from Candida adapts to the conformational variability of the various
      substates of the substrates by small, local adjustments within the binding
      pocket. In contrast, the more constrained pocket of the lipase from Thermomyces
      adapts by adjusting through concerted global motions between subdomains. This
      leads to the identification of one large pocket in Candida that accommodates both
      the sucrose and the lauroyl moieties of the transition state, whereas in
      Thermomyces the binding pocket is smaller, leading to the localization of the two
      moieties in two distinct pockets; this partly rationalizes the broader
      specificity of the former relative to the latter. Mutations have been suggested
      to exploit the differences towards changing the observed selectivities.

PMID- 15557257
TI  - Infrequent cavity-forming fluctuations in HPr from Staphylococcus carnosus
      revealed by pressure- and temperature-dependent tyrosine ring flips.
AB  - Infrequent structural fluctuations of a globular protein is seldom detected and
      studied in detail. One tyrosine ring of HPr from Staphylococcus carnosus, an 88
      residue phosphocarrier protein with no disulfide bonds, undergoes a very slow
      ring flip, the pressure and temperature dependence of which is studied in detail
      using the on-line cell high-pressure nuclear magnetic resonance technique in the
      pressure range from 3 MPa to 200 MPa and in the temperature range from 257 K to
      313 K. The ring of Tyr6 is buried sandwiched between a beta-sheet and alpha
      helices (the water-accessible area is less than 0.26 nm2), its hydroxyl proton
      being involved in an internal hydrogen bond. The ring flip rates 10(1)-10(5) s(
      1) were determined from the line shape analysis of H(delta1, delta2) and
      H(epsilon1,epsilon2) of Tyr6, giving an activation volume DeltaV++ of 0.044 +/-
      0.008 nm3 (27 mL mol(-1)), an activation enthalpy DeltaH++ of 89 +/- 10 kJ mol(
      1), and an activation entropy DeltaS++ of 16 +/- 2 JK(-1) mol(-1). The DeltaV++)
      and DeltaH++ values for HPr found previously for Tyr and Phe ring flips of BPTI
      and cytochrome c fall within the range of DeltaV(double dagger) of 28 to 51 mL
      mol(-1) and DeltaH++ of 71 to 155 kJ mol(-1). The fairly common DeltaV++ and
      DeltaH++ values are considered to represent the extra space or cavity required
      for the ring flip and the extra energy required to create a cavity, respectively,
      in the core part of a globular protein. Nearly complete cold denaturation was
      found to take place at 200 MPa and 257 K independently from the ring
      reorientation process.

PMID- 15557258
TI  - Solvation and the hidden thermodynamics of a zinc finger probed by nonstandard
      repair of a protein crevice.
AB  - The classical Zn finger contains a phenylalanine at the crux of its three
      architectural elements: a beta-hairpin, an alpha-helix, and a Zn(2+)-binding
      site. Surprisingly, phenylalanine is not required for high-affinity Zn2+ binding,
      but instead contributes to the specification of a precise DNA-binding surface.
      Substitution of phenylalanine by leucine leads to a floppy but native-like
      structure whose Zn affinity is maintained by marked entropy-enthalpy compensation
      (DeltaDeltaH -8.3 kcal/mol and -TDeltaDeltaS 7.7 kcal/mol). Phenylalanine and
      leucine differ in shape, size, and aromaticity. To distinguish which features
      correlate with dynamic stability, we have investigated a nonstandard finger
      containing cyclohexanylalanine at this site. The structure of the nonstandard
      finger is similar to that of the native domain. The cyclohexanyl ring assumes a
      chair conformation, and conformational fluctuations characteristic of the leucine
      variant are damped. Although the nonstandard finger exhibits a lower affinity for
      Zn2+ than does the native domain (DeltaDeltaG -1.2 kcal/mol), leucine-associated
      perturbations in enthalpy and entropy are almost completely attenuated
      (DeltaDeltaH -0.7 kcal/mol and -TDeltaDeltaS -0.5 kcal/mol). Strikingly, global
      changes in entropy (as inferred from calorimetry) are in each case opposite in
      sign from changes in configurational entropy (as inferred from NMR). This seeming
      paradox suggests that enthalpy-entropy compensation is dominated by solvent
      reorganization rather than nominal molecular properties. Together, these results
      demonstrate that dynamic and thermodynamic perturbations correlate with formation
      or repair of a solvated packing defect rather than type of physical interaction
      (aromatic or aliphatic) within the core.

PMID- 15557259
TI  - Simulation of the activation of alpha-chymotrypsin: analysis of the pathway and
      role of the propeptide.
AB  - Alpha-chymotrypsin undergoes a reversible conformational change from an inactive
      chymotrypsinogen-like structure at high pH to an active conformation at neutral
      pH. In order to gain insight into this process on a structural level, we applied
      molecular dynamics and targeted molecular dynamics simulations in aqueous
      environment on the activation and inactivation processes of three different types
      of chymotrypsin. These are the wild-type bovine chymotrypsin containing the
      propeptide and the bovine and rat chymotrypsin lacking the propeptide. From these
      simulations, the importance of the propeptide and of the sequence differences
      between the rat and bovine variants from the viewpoint of activation could be
      evaluated and compared with previous fluorescence stopped flow results. The
      obtained results show the unambiguous influence of the propeptide on the explored
      conformational space, whereas the sequence differences between bovine and rat
      chymotrypsin play a minor role. The main features of activation are present in
      both the wild type and the variant lacking the propeptide, despite the fact that
      different parts of the conformational space were explored. The comparison of all
      trajectories shows that particular amino acid residues, such as 17, 18, 19, 187,
      217, 218, and 223, undergo large dihedral transitions during the activation
      process, suggesting a role as hinge residues during the conformational change.

PMID- 15557260
TI  - Structural and functional analysis of the gpsA gene product of Archaeoglobus
      fulgidus: a glycerol-3-phosphate dehydrogenase with an unusual NADP+ preference.
AB  - NAD(+)-dependent glycerol-3-phosphate dehydrogenase (G3PDH) is generally absent
      in archaea, because archaea, unlike eukaryotes and eubacteria, utilize glycerol-1
      phosphate instead of glycerol-3-phosphate for the biosynthesis of membrane
      lipids. Surprisingly, the genome of the hyperthermophilic archaeon Archaeoglobus
      fulgidus comprises a G3PDH ortholog, gpsA, most likely due to horizontal gene
      transfer from a eubacterial organism. Biochemical characterization proved G3PDH
      like activity of the recombinant gpsA gene product. However, unlike other G3PDHs,
      the up to 85 degrees C thermostable A. fulgidus G3PDH exerted a 15-fold
      preference for NADPH over NADH. The A. fulgidus G3PDH bears the hallmarks of
      adaptation to halotolerance and thermophilicity, because its 1.7-A crystal
      structure showed a high surface density for negative charges and 10 additional
      intramolecular salt bridges compared to a mesophilic G3PDH structure. Whereas all
      amino acid residues required for dihydroxyacetone phosphate binding and reductive
      catalysis are highly conserved, the binding site for the adenine moiety of the
      NAD(P) cosubstrate shows a structural variation that reflects the observed NADPH
      preference, for example, by a putative salt bridge between R49 and the 2'
      phosphate.

PMID- 15557261
TI  - A model of the acid sphingomyelinase phosphoesterase domain based on its remote
      structural homolog purple acid phosphatase.
AB  - Sequence profile and fold recognition methods identified mammalian purple acid
      phosphatase (PAP), a member of a dimetal-containing phosphoesterase (DMP) family,
      as a remote homolog of human acid sphingomyelinase (ASM). A model of the
      phosphoesterase domain of ASM was built based on its predicted secondary
      structure and the metal-coordinating residues of PAP. Due to the low sequence
      identity between ASM and PAP (approximately 15%), the highest degree of
      confidence in the model resides in the metal-binding motifs. The ASM model
      predicts residues Asp 206, Asp 278, Asn 318, His 425, and His 457 to be dimetal
      coordinating. A putative orientation for the phosphorylcholine head group of the
      ASM substrate, sphingomyelin (SM), was made based on the predicted catalysis of
      the phosphorus-oxygen bond in the active site of ASM and on a structural
      comparison of the PAP-phosphate complex to the C-reactive protein
      phosphorylcholine complex. These complexes revealed similar spatial interactions
      between the metal-coordinating residues, the metals, and the phosphate groups,
      suggesting a putative orientation for the head group in ASM consistent with the
      mechanism considerations. A conserved sequence motif in ASM, NX3CX3N, was
      identified (Asn 381 to Asn 389) and is predicted to interact with the choline
      amine moiety in SM. The resulting ASM model suggests that the enzyme uses an SN2
      type catalytic mechanism to hydrolyze SM, similar to other DMPs. His 319 in ASM
      is predicted to protonate the ceramide-leaving group in the catalysis of SM. The
      putative functional roles of several ASM Niemann-Pick missense mutations, located
      in the predicted phosphoesterase domain, are discussed in context to the model.

PMID- 15557262
TI  - On the use of DXMS to produce more crystallizable proteins: structures of the T.
      maritima proteins TM0160 and TM1171.
AB  - The structure of two Thermotoga maritima proteins, a conserved hypothetical
      protein (TM0160) and a transcriptional regulator (TM1171), have now been
      determined at 1.9 A and 2.3 A resolution, respectively, as part of a large-scale
      structural genomics project. Our first efforts to crystallize full-length
      versions of these targets were unsuccessful. However, analysis of the recombinant
      purified proteins using the technique of enhanced amide hydrogen/deuterium
      exchange mass spectroscopy (DXMS) revealed substantial regions of rapid amide
      deuterium hydrogen exchange, consistent with flexible regions of the structures.
      Based on these exchange data, truncations were designed to selectively remove the
      disordered C-terminal regions, and the resulting daughter proteins showed greatly
      enhanced crystallizability. Comparative DXMS analysis of full-length protein
      versus truncated forms demonstrated complete and exact preservation of the
      exchange rate profiles in the retained sequence, indicative of conservation of
      the native folded structure. This study presents the first structures produced
      with the aid of the DXMS method for salvaging intractable crystallization
      targets. The structure of TM0160 represents a new fold and highlights the use of
      this approach where any prior structural knowledge is absent. The structure of
      TM1171 represents an example where the lack of a substrate/cofactor may impair
      crystallization. The details of both structures are presented and discussed.

PMID- 15557264
TI  - Specific recognition of a dsDNA sequence motif by an immunoglobulin VH homodimer.
AB  - Anti-DNA antibodies have the potential to be applied in vast fields of
      fundamental as well as medical research. They are found in autoimmune diseases,
      such as systemic lupus erythemotosus. In most cases, anti-dsDNA antibodies do not
      present sequence specificity and are of low affinity. The dominant role of VH
      domains in DNA recognition induced us to search for binders based on VH dimers
      (VHD), previously reported to bind different protein antigens. We screened a
      phage displayed homo-VHD library against a 19-bp dsDNA sequence. A sequence
      specific binder was selected, which recognizes the terminal located CTGC motif
      with a Kd of 250 nM. Association of the two identical VH domains of the molecule
      was shown to be essential for binding.

PMID- 15557263
TI  - Molecular modeling of family GH16 glycoside hydrolases: potential roles for
      xyloglucan transglucosylases/hydrolases in cell wall modification in the poaceae.
AB  - Family GH16 glycoside hydrolases can be assigned to five subgroups according to
      their substrate specificities, including xyloglucan transglucosylases/hydrolases
      (XTHs), (1,3)-beta-galactanases, (1,4)-beta-galactanases/kappa-carrageenases,
      "nonspecific" (1,3/1,3;1,4)-beta-D-glucan endohydrolases, and (1,3;1,4)-beta-D
      glucan endohydrolases. A structured family GH16 glycoside hydrolase database has
      been constructed (http://www.ghdb.uni-stuttgart.de) and provides multiple
      sequence alignments with functionally annotated amino acid residues and
      phylogenetic trees. The database has been used for homology modeling of seven
      glycoside hydrolases from the GH16 family with various substrate specificities,
      based on structural coordinates for (1,3;1,4)-beta-D-glucan endohydrolases and a
      kappa-carrageenase. In combination with multiple sequence alignments, the models
      predict the three-dimensional (3D) dispositions of amino acid residues in the
      substrate-binding and catalytic sites of XTHs and (1,3/1,3;1,4)-beta-d-glucan
      endohydrolases; there is no structural information available in the databases for
      the latter group of enzymes. Models of the XTHs, compared with the recently
      determined structure of a Populus tremulos x tremuloides XTH, reveal similarities
      with the active sites of family GH11 (1,4)-beta-D-xylan endohydrolases. From a
      biological viewpoint, the classification, molecular modeling and a new 3D
      structure of the P. tremulos x tremuloides XTH establish structural and
      evolutionary connections between XTHs, (1,3;1,4)-beta-D-glucan endohydrolases and
      xylan endohydrolases. These findings raise the possibility that XTHs from higher
      plants could be active not only on cell wall xyloglucans, but also on (1,3;1,4)
      beta-D-glucans and arabinoxylans, which are major components of walls in grasses.
      A role for XTHs in (1,3;1,4)-beta-D-glucan and arabinoxylan modification would be
      consistent with the apparent overrepresentation of XTH sequences in cereal
      expressed sequence tags databases.

PMID- 15557265
TI  - Comparative computational analysis of prion proteins reveals two fragments with
      unusual structural properties and a pattern of increase in hydrophobicity
      associated with disease-promoting mutations.
AB  - Prion diseases are a group of neurodegenerative disorders associated with
      conversion of a normal prion protein, PrPC, into a pathogenic conformation,
      PrPSc. The PrPSc is thought to promote the conversion of PrPC. The structure and
      stability of PrPC are well characterized, whereas little is known about the
      structure of PrPSc, what parts of PrPC undergo conformational transition, or how
      mutations facilitate this transition. We use a computational knowledge-based
      approach to analyze the intrinsic structural propensities of the C-terminal
      domain of PrP and gain insights into possible mechanisms of structural
      conversion. We compare the properties of PrP sequences to those of a PrP paralog,
      Doppel, and to the distributions of structural propensities observed in known
      protein structures from the Protein Data Bank. We show that the prion protein
      contains at least two sequence fragments with highly unusual intrinsic
      propensities, PrP(114-125) and helix B. No segments with unusual properties were
      found in Doppel protein, which is topologically identical to PrP but does not
      undergo structural rearrangements. Known disease-promoting PrP mutations form a
      statistically significant cluster in the region comprising helices B and C. Due
      to their unusual properties, PrP(114-125) and the C terminus of helix B may be
      considered as primary candidates for sites involved in conformational transition
      from PrPC to PrPSc. The results of our study also show that most PrP mutations
      associated with neurodegenerative disorders increase local hydrophobicity. We
      suggest that the observed increase in hydrophobicity may facilitate PrP-to-PrP
      or/and PrP-to-cofactor interactions, and thus promote structural conversion.

PMID- 15557266
TI  - Correspondence between anomalous m- and DeltaCp-values in protein folding.
AB  - Proteins folding according to a classical two-state system characteristically
      show V-shaped chevron plots. We have previously interpreted the symmetrically
      curved chevron plot of the protein U1A as denaturant-dependent movements in the
      position of the transition state ensemble (TSE). S6, a structural analog of U1A,
      shows a classical V-shaped chevron plot indicative of straightforward two-state
      kinetics, but the mutant LA30 has a curved unfolding limb, which is most
      consistent with TSE mobility. The kinetic m-values (derivatives of the rate
      constants with respect to denaturant concentration) in themselves depend on
      denaturant concentration. To obtain complementary information about putative
      mobile TSEs, we have carried out a thermodynamic analysis of the three proteins,
      based on data for refolding and unfolding over the range 10 degrees C to 70
      degrees C. The data at all temperatures can be fitted to two-state model systems.
      Importantly, for all three proteins the activation heat capacities are, within
      error, identical to the heat capacities measured in independent experiments under
      equilibrium conditions. Although the equilibrium heat capacities are essentially
      invariant with regard to denaturant concentration, the activation heat
      capacities, similar to the structurally equivalent kinetic m-values, show marked
      denaturant dependence. Furthermore, the values of beta++ at different denaturant
      concentrations measured by m-values and by heat capacity values are very similar.
      These observations are consistent with significant transition state movements
      within the framework of two-state folding. The basis for TSE movement appears to
      be enthalpic rather than entropic, suggesting that the binding energy of
      denaturant-protein interactions is a major determinant of the response of energy
      landscape contours to changing environments.

PMID- 15557267
TI  - Studies on recombinant single chain Jacalin lectin reveal reduced affinity for
      saccharides despite normal folding like native Jacalin.
AB  - Sugar binding studies, inactivation, unfolding, and refolding of native Jacalin
      (nJacalin) from Artocarpus integrifolia and recombinant single-chain Jacalin
      (rJacalin) expressed in Escherichia coli were studied by intrinsic fluorescence
      and thermal and chemical denaturation approaches. Interestingly, rJacalin does
      not undergo any proteolytic processing in an E. coli environment. It has 100fold
      less affinity for methyl-alpha-galactose (Ka: 2.48 x 10(2)) in comparison to
      nJacalin (Ka: 1.58 x 10(4)), and it also binds Thomsen-Friedenreich (TF)
      disaccharide (Galbeta1-3GalNAc) with less affinity. Overall sugar binding
      characteristics of rJacalin are qualitatively similar to that of nJacalin
      (Gal<MealphaGal<MealphaTFdisaccharide). Circular dichroism studies at near- and
      far-UV, thermal, and chemical denaturation studies reveal that the rJacalin
      behaves like nJacalin. Guanidine hydrochloride-induced denaturation, followed by
      renaturation, yielded total recovery of sugar binding activity of rJacalin in
      comparison to partial recovery for nJacalin. This signifies the minor changes in
      the refolding pathways between native and recombinant lectins. The stability of
      rJacalin is dramatically reduced in the extreme pH range unlike nJacalin. Both
      lectins do not bind 1-anilino-8-naphthalene sulfonic acid (ANS) in the pH range
      of 5 to 12 but they do in the pH range of 1-3. Solute quenching studies of the
      lectin using acrylamide, KI, and CsCl indicated that the tryptophan residues have
      full accessibility to the neutral quencher and poor accessibility to ionic
      quenchers. In summary, biophysical and biochemical studies on the native versus
      recombinant Jacalin suggest that post-translational modification, i.e., the
      processing of Jacalin into two chains is probably not a prerequisite for sugar
      binding but may be required for higher affinity.

PMID- 15557268
TI  - Expression and purification of recombinant proteins from Escherichia coli:
      Comparison of an elastin-like polypeptide fusion with an oligohistidine fusion.
AB  - Thermally responsive elastin like polypeptides (ELPs) can be used to purify
      proteins from Escherichia coli culture when proteins are expressed as a fusion
      with an ELP. Nonchromatographic purification of ELP fusion proteins, termed
      inverse transition cycling (ITC), exploits the reversible soluble-insoluble phase
      transition behavior imparted by the ELP tag. Here, we quantitatively compare the
      expression and purification of ELP and oligohistidine fusions of chloramphenicol
      acetyltransferase (CAT), blue fluorescent protein (BFP), thioredoxin (Trx), and
      calmodulin (CalM) from both a 4-h culture with chemical induction of the plasmid
      borne fusion protein gene and a 24-h culture without chemical induction. The
      total protein content and functional activity were quantified at each ITC
      purification step. For CAT, BFP, and Trx, the 24-h noninduction culture of ELP
      fusion proteins results in a sevenfold increase in the yield of each fusion
      protein compared to that obtained by the 4-h-induced culture, and the calculated
      target protein yield is similar to that of their equivalent oligohistidine
      fusion. For these proteins, ITC purification of fusion proteins also results in
      approximately 75% recovery of active fusion protein, similar to affinity
      chromatography. Compared to chromatographic purification, however, ITC is
      inexpensive, requires no specialized equipment or reagents, and because ITC is a
      batch purification process, it is easily scaled up to accommodate larger culture
      volumes or scaled down and multiplexed for high-throughput, microscale
      purification; thus, potentially impacting both high-throughput protein expression
      and purification for proteomics and large scale, cost-effective industrial
      bioprocessing of pharmaceutically relevant proteins.

PMID- 15557269
TI  - Biochemical properties of V91G calmodulin: A calmodulin point mutation that
      deregulates muscle contraction in Drosophila.
AB  - A mutation (Cam7) to the single endogenous calmodulin gene of Drosophila
      generates a mutant protein with valine 91 changed to glycine (V91G D-CaM). This
      mutation produces a unique pupal lethal phenotype distinct from that of a null
      mutation. Genetic studies indicate that the phenotype reflects deregulation of
      calcium fluxes within the larval muscles, leading to hypercontraction followed by
      muscle failure. We investigated the biochemical properties of V91G D-CaM. The
      effects of the mutation on free CaM are minor: Calcium binding, and overall
      secondary and tertiary structure are indistinguishable from those of wild type. A
      slight destabilization of the C-terminal domain is detectable in the calcium-free
      (apo-) form, and the calcium-bound (holo-) form has a somewhat lower surface
      hydrophobicity. These findings reinforce the indications from the in vivo work
      that interaction with a specific CaM target(s) underlies the mutant defects. In
      particular, defective regulation of ryanodine receptor (RyR) channels was
      indicated by genetic interaction analysis. Studies described here establish that
      the putative CaM binding region of the Drosophila RyR (D-RyR) binds wild-type D
      CaM comparably to the equivalent CaM-RyR interactions seen for the mammalian
      skeletal muscle RyR channel isoform (RYR1). The V91G mutation weakens the
      interaction of both apo- and holo-D-CaM with this binding region, and decreases
      the enhancement of the calcium-binding affinity of CaM that is detectable in the
      presence of the RyR target peptide. The predicted functional consequences of
      these changes are consonant with the in vivo phenotype, and indicate that D-RyR
      is one, if not the major, target affected by the V91G mutation in CaM.

PMID- 15557270
TI  - Probabilistic cross-link analysis and experiment planning for high-throughput
      elucidation of protein structure.
AB  - Emerging high-throughput techniques for the characterization of protein and
      protein-complex structures yield noisy data with sparse information content,
      placing a significant burden on computation to properly interpret the
      experimental data. One such technique uses cross-linking (chemical or by cysteine
      oxidation) to confirm or select among proposed structural models (e.g., from fold
      recognition, ab initio prediction, or docking) by testing the consistency between
      cross-linking data and model geometry. This paper develops a probabilistic
      framework for analyzing the information content in cross-linking experiments,
      accounting for anticipated experimental error. This framework supports a
      mechanism for planning experiments to optimize the information gained. We
      evaluate potential experiment plans using explicit trade-offs among key
      properties of practical importance: discriminability, coverage, balance,
      ambiguity, and cost. We devise a greedy algorithm that considers those properties
      and, from a large number of combinatorial possibilities, rapidly selects sets of
      experiments expected to discriminate pairs of models efficiently. In an
      application to residue-specific chemical cross-linking, we demonstrate the
      ability of our approach to plan experiments effectively involving combinations of
      cross-linkers and introduced mutations. We also describe an experiment plan for
      the bacteriophage lambda Tfa chaperone protein in which we plan dicysteine
      mutants for discriminating threading models by disulfide formation. Preliminary
      results from a subset of the planned experiments are consistent and demonstrate
      the practicality of planning. Our methods provide the experimenter with a
      valuable tool (available from the authors) for understanding and optimizing cross
      linking experiments.

PMID- 15557272
TI  - 2004 Irving Sigal Young Investigator Award.

PMID- 15557273
TI  - Metabolism in the era of molecular biology.

PMID- 15557274
TI  - The interferon-inducible p204 protein acts as a transcriptional coactivator of
      Cbfa1 and enhances osteoblast differentiation.
AB  - The differentiation of uncommitted mesenchymal cells into osteoblasts is a
      fundamental molecular event governing both embryonic development and bone repair.
      The bone morphogenetic proteins (BMPs) are important regulators of this process;
      they function by binding to cell surface receptors and signaling by means of Smad
      proteins. Core binding factor alpha-1 (Cbfa1), a member of the runt family of
      transcription factors, is an essential transcriptional regulator of osteoblast
      differentiation and bone formation, and this process is positively or negatively
      regulated by a variety of coactivators and corepressors. We report that p204, an
      interferon-inducible protein that was previously shown to inhibit cell
      proliferation and promote the differentiation of myoblasts to myotubes, is a
      novel regulator in the course of osteogenesis. p204 is expressed in embryonic
      osteoblasts and hypertrophic chondrocytes in the growth plate as well as in the
      calvaria osteoblasts of neonatal mice. Its level is increased in the course of
      the BMP-2-triggered osteoblast differentiation of pluripotent C2C12 cells. This
      increase is probably due to the activation of the gene encoding 204 (Ifi204) by
      Smad transcription factor, including Smad1, -4, and -5. Overexpression of p204
      enhances the BMP-2-induced osteoblast differentiation in vitro, as revealed by
      elevated alkaline phosphatase activity and osteocalcin production. p204 acts as a
      cofactor of Cbfa1: 1) high levels of p204 augment, whereas the lowering of p204
      level decreases, the Cbfa1-dependent transcription, and 2) p204 associates with
      Cbfa1 both in vitro and in vivo. Two nonoverlapping segments in p204 bind to
      Cbfa1, and the N-terminal 88-amino acid segment of Cbfa1 is required for binding
      to p204. p204, which is the first interferon-inducible protein found to associate
      with Cbfa1, functions as a novel regulator of osteoblast differentiation.

PMID- 15557275
TI  - Endogenous protein kinase inhibitor gamma terminates immediate-early gene
      expression induced by cAMP-dependent protein kinase (PKA) signaling: termination
      depends on PKA inactivation rather than PKA export from the nucleus.
AB  - Expression of many genes induced by cAMP-dependent protein kinase (PKA) signaling
      is rapidly terminated. Although many mechanisms contribute to regulation of PKA
      signaling, members of the endogenous protein kinase inhibitor (PKI) family may be
      particularly important for terminating nuclear PKA activity and gene expression.
      Here we used both siRNA and antisense knockdown strategies to examine PKA
      signaling activated by parathyroid hormone or the beta-adrenergic agonist,
      isoproterenol. We found that endogenous PKIgamma is required for efficient
      termination of nuclear PKA activity, transcription factor phosphorylation, and
      immediate-early genes. Moreover, PKIgamma is required for export of PKA catalytic
      subunits from the nucleus back to the cytoplasm following activation of PKA
      signaling because this is also inhibited by PKIgamma knockdown. Leptomycin B
      blocks PKA nuclear export but has little or no effect on nuclear PKA activity or
      immediate-early gene expression. Thus, inactivation of PKA activity in the
      nucleus is sufficient to terminate signaling, and nuclear export is not required.
      These results were the first in any cell type showing that endogenous levels of
      PKI regulate PKA signaling.

PMID- 15557276
TI  - Novel 70-kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique
      heterogeneous sulfation pattern from shark skin, which exhibit neuritogenic
      activity and binding activities for growth factors and neurotrophic factors.
AB  - Chondroitin sulfate (CS) and dermatan sulfate (DS) hybrid chains of proteoglycans
      are critical in growth factor binding, neuritogenesis, and brain development.
      Here we isolated CS/DS hybrid chains from shark skin aiming to develop
      therapeutic agents. Digestion with various chondroitinases showed that both GlcUA
      and IdoUA-containing disaccharides are scattered along the polysaccharide chains
      with an unusually large average molecular mass of 70 kDa. The CS/DS chains were
      separated into major (80%) and minor (20%) fractions by anion-exchange
      chromatography. Both fractions had relatively low degrees of sulfation
      (sulfate/disaccharide molar ratio=1.17 versus 0.87), showing a unique feature
      compared with the marine CS and DS isolated to date, most of which are
      oversulfated. They were highly heterogeneous and characterized by multiple
      disaccharides including GlcUA-GalNAc, GlcUA-GalNAc(6S), GlcUA-GalNAc(4S), IdoUA
      GalNAc(4S), GlcUA-GalNAc(4S,6S), IdoUA-GalNAc(4S,6S), GlcUA(2S)-GalNAc(6S),
      and/or IdoUA(2S)-GalNAc(6S), IdoUA(2S)-GalNAc(4S) and novel GlcUA(2S)-GalNAc(4S),
      where 2S, 4S, and 6S represent 2-O-, 4-O- and 6-O-sulfate, respectively. The
      CS/DS chains bound two neurotrophic factors and various growth factors expressed
      in the brain with high affinity as evaluated for the major fraction by kinetic
      analysis using a surface plasmon resonance detector, and also promoted the
      outgrowth of neurites of both an axonic and a dendritic nature. The neuritogenic
      activity was abolished completely by digestion with chondroitinase ABC, AC-I, or
      B, suggesting the importance of both GlcUA- and IdoUA-containing moieties. It
      also showed anti-heparin cofactor II activity comparable to that exhibited by DS
      from porcine skin. Thus, by virtue of its unique structure and biological
      activities, DS will find a potential use in therapeutics.

PMID- 15557277
TI  - cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c
      oxidase activity.
AB  - Signaling pathways targeting mitochondria are poorly understood. We here examine
      phosphorylation by the cAMP-dependent pathway of subunits of cytochrome c oxidase
      (COX), the terminal enzyme of the electron transport chain. Using anti-phospho
      antibodies, we show that cow liver COX subunit I is tyrosinephosphorylated in the
      presence of theophylline, a phosphodiesterase inhibitor that creates high cAMP
      levels, but not in its absence. The site of phosphorylation, identified by mass
      spectrometry, is tyrosine 304 of COX catalytic subunit I. Subunit I
      phosphorylation leads to a decrease of V(max) and an increase of K(m) for
      cytochrome c and shifts the reaction kinetics from hyperbolic to sigmoidal such
      that COX is fully or strongly inhibited up to 10 mum cytochrome c substrate
      concentrations, even in the presence of allosteric activator ADP. To assess our
      findings with the isolated enzyme in a physiological context, we tested the
      starvation signal glucagon on human HepG2 cells and cow liver tissue. Glucagon
      leads to COX inactivation, an effect also observed after incubation with adenylyl
      cyclase activator forskolin. Thus, the glucagon receptor/G-protein/cAMP pathway
      regulates COX activity. At therapeutic concentrations used for asthma relief,
      theophylline causes lung COX inhibition and decreases cellular ATP levels,
      suggesting a mechanism for its clinical action.

PMID- 15557278
TI  - Activation of the phagocyte NADPH oxidase by Rac Guanine nucleotide exchange
      factors in conjunction with ATP and nucleoside diphosphate kinase.
AB  - Activation of the phagocyte NADPH oxidase is the consequence of the assembly of
      membranal cytochrome b559 with the cytosolic components p47phox, p67phox, and the
      GTPase Rac and is mimicked by a cell-free system comprising these components and
      an activator. We designed a variant of this system, consisting of membranes,
      p67phox) prenylated Rac1-GDP, and the Rac-specific guanine nucleotide exchange
      factor (GEF) Trio, in which oxidase activation is induced in the absence of an
      activator and p47phox. We now show that: 1) Trio and another Rac GEF (Tiam1) act
      by inducing GDP to GTP exchange on prenylated Rac1-GDP and that our earlier
      assertion that activation is GTP-independent is explained by contamination of
      p67phox preparations with GTP and/or ATP. 2) Oxidase activation by Rac GEFs is
      supported not only by GTP but also by ATP. 3) Non-hydrolysable GTP analogs are
      active, whereas ATP analogs, incapable of gamma-phosphoryl transfer, are
      inactive. 4) The ability of ATP to support GEF-induced oxidase activation is
      explained by ATP serving as a gamma-phosphoryl donor for a membrane-localized
      nucleoside diphosphate kinase (NDPK), converting GDP to GTP. 5) The existence of
      a NDPK in macrophage membranes is proven by functional, enzymatic, and
      immunologic criteria. 6) NDPK acts on free GDP, and the newly formed GTP is bound
      again to Rac. 7) Free GDP is derived exclusively by dissociation from prenylated
      Rac1-GDP, mediated by GEF. NDPK and GEF appear to be functionally linked in the
      sense that the availability of GDP, serving as substrate for NDPK, is dependent
      on the level of activity of GEF.

PMID- 15557279
TI  - Alzheimer's Abeta40 studied by NMR at low pH reveals that sodium 4,4-dimethyl-4
      silapentane-1-sulfonate (DSS) binds and promotes beta-ball oligomerization.
AB  - The Alzheimer's Abeta40 peptide forms soluble oligomers that are extremely potent
      neurotoxins and strongly impede synapses function. In this study the formation
      and structure of the large, soluble, neurotoxic Abeta40 oligomer called "beta
      ball" were characterized by two-dimensional NMR, circular dichroism, fluorescence
      spectroscopy, hydrogen exchange, and equilibrium sedimentation. In acidic aqueous
      solution, half the Abeta40 molecules are in the beta-ball state; the remainder
      are monomeric. The equilibrium between the two states is slow as judged by NMR
      linewidths and is stable for months. The kinetics of beta-ball formation from
      monomer are biphasic with tau1 = 7 min and tau2 = 80 min with no transient helix
      formation. Monomeric Abeta40 is essentially devoid of stable secondary structure,
      although the central, Leu17-Ala21, and C-terminal, Gly29-Val40, hydrophobic
      regions show propensity toward adopting extended structure, and residues 22-25
      tended to form a turn. We found that sodium 4,4-dimethyl-4-silapentane-1
      sulfonate (DSS) binds to the central hydrophobic region of monomeric Abeta40. DSS
      binds beta-balls more strongly and caused them to double in size. Plausible
      micelle-like models for the beta-ball structure with and without bound DSS are
      presented.

PMID- 15557280
TI  - p27Kip1 and cyclin D1 are necessary for focal adhesion kinase regulation of cell
      cycle progression in glioblastoma cells propagated in vitro and in vivo in the
      scid mouse brain.
AB  - We have reported previously that the expression of focal adhesion kinase (FAK) is
      elevated in glioblastomas and that expression of FAK promotes the proliferation
      of glioblastoma cells propagated in either soft agar or in the C.B.17 severe
      combined immunodeficiency (scid) mouse brain. We therefore determined the effect
      of FAK on cell cycle progression in these cells. We found that overexpression of
      wild-type FAK promoted exit from G(1) in monolayer cultures of glioblastoma
      cells, enhanced the expression of cyclins D1 and E while reducing the expression
      of p27(Kip1) and p21(Waf1), and enhanced the kinase activity of the cyclin D1
      cyclin-dependent kinase-4 (cdk4) complex. Transfection of the monolayers with a
      FAK molecule in which the autophosphorylation site is mutated (FAK397F) inhibited
      exit from G(1) and reduced the expression of cyclins D1 and E while enhancing the
      expression of p27(Kip1) and p21(Waf1). Small interfering RNA (siRNA)-mediated
      down-regulation of cyclin D1 inhibited the enhancement of cell cycle progression
      observed on expression of wild-type FAK, whereas siRNA-mediated down-regulation
      of cyclin E had no effect. siRNA-mediated down-regulation of p27(Kip1) overcame
      the inhibition of cell cycle progression observed on expression of FAK397F,
      whereas down-regulation of p21(Waf1) had no effect. These results were confirmed
      in vivo in the scid mouse brain xenograft model in which propagation of
      glioblastoma cells expressing FAK397F resulted in a 50% inhibition of tumor
      growth and inhibited exit from G(1). Taken together, our results indicate that
      FAK promotes proliferation of glioblastoma cells by enhancing exit from G(1)
      through a mechanism that involves cyclin D1 and p27(Kip1).

PMID- 15557281
TI  - ICI182,780 induces p21Waf1 gene transcription through releasing histone
      deacetylase 1 and estrogen receptor alpha from Sp1 sites to induce cell cycle
      arrest in MCF-7 breast cancer cell line.
AB  - We used the estrogen-responsive MCF-7 breast cancer cell line as a relevant model
      to study the anti-proliferative effects of ICI182,780 and identified the negative
      cell cycle regulator p21Waf1 as a specific target of ICI182,780. Furthermore,
      silencing of the p21Waf1 expression by small interfering RNA overcame the G0/G1
      cell cycle arrest induced by ICI182,780, suggesting that the induction of p21Waf1
      expression has a direct role in mediating the ICI182,780-induced G0/G1 arrest. We
      further demonstrated that the induction of p21Waf1 by ICI182,780 is mediated at
      transcriptional and gene promoter levels through the proximal Sp1 sites located
      near the transcription start site. Co-immunoprecipitation, DNA "pull-down," and
      chromatin immunoprecipitation experiments together showed that in cycling cells,
      estrogen receptor alpha and histone deacetylase 1 (HDAC1) are recruited to the
      proximal Sp1 sites of the promoter to repress p21Waf1 expression. In the presence
      of ICI182,780, estrogen receptor alpha and HDACs are dissociated from Sp1,
      resulting in increased histone acetylation and de-repression of the p21Waf1
      promoter and induction of p21Waf1 expression. The fact that p21Waf1 expression is
      normally repressed by HDAC activity in cycling cells is further demonstrated by
      the finding that p21Waf1 transcription can be induced by the silencing of HDACs
      with small interfering RNA or treatment with HDAC inhibitors.

PMID- 15557282
TI  - Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating
      integrin alpha6-mediated cell adhesion.
AB  - Tetraspanin CD82 has been implicated in integrin-mediated functions such as cell
      motility and invasiveness. Although tetraspanins associate with integrins, it is
      unknown if and how CD82 regulates the functionality of integrins. In this study,
      we found that Du145 prostate cancer cells underwent morphogenesis on the
      reconstituted basement membrane Matrigel to form an anastomosing network of
      multicellular structures. This process entirely depends on integrin alpha6, a
      receptor for laminin. After CD82 is expressed in Du145 cells, this cellular
      morphogenesis was abolished, indicating a functional cross-talk between CD82 and
      alpha6 integrins. Interestingly, antibodies against other tetraspanins expressed
      in Du145 cells such as CD9, CD81, and CD151 did not block this integrin alpha6
      dependent morphogenesis. We further found that CD82 significantly inhibited cell
      adhesion on laminin 1. Notably, the level of alpha6 integrins on the cell surface
      was down-regulated upon CD82 expression, although total cellular alpha6 protein
      levels remained unchanged in CD82-expressing cells. This down-regulation
      indicates that the diminished cell adhesiveness of CD82-expressing Du145 cells on
      laminin likely resulted from less cell surface expression of alpha6 integrins. As
      expected, CD82 physically associated with the integrin alpha6 in Du145-CD82
      transfectant cells, suggesting that the formation of the CD82-integrin alpha6
      complex reduces alpha6 integrin cell surface expression. Finally, the
      internalization of cell surface integrin alpha6 is significantly enhanced upon
      CD82 expression. In conclusion, our results indicate that 1) CD82 attenuates
      integrin alpha6 signaling during a cellular morphogenic process; 2) the decreased
      surface expression of alpha6 integrins in CD82-expressing cells is likely
      responsible for the diminished adhesiveness on laminin and, subsequently, results
      in the attenuation of alpha6 integrin-mediated cellular morphogenesis; and 3) the
      accelerated internalization of integrin alpha6 upon CD82 expression correlates
      with the down-regulation of cell surface integrin alpha6.

PMID- 15557283
TI  - Bidirectional replication initiates at sites throughout the mitochondrial genome
      of birds.
AB  - Analysis of mitochondrial replication intermediates of Gallus gallus on fork
      direction gels indicates that replication occurs in both directions around
      circular mitochondrial DNA. This finding was corroborated by a study of chick
      mitochondrial DNA on standard neutral two-dimensional agarose gels, which yielded
      archetypal initiation arcs in fragments covering the entire genome. There was,
      however, considerable variation in initiation arc intensity. The majority of
      initiation events map to regions flanking the major non-coding region, in
      particular the NADH dehydrogenase subunit 6 (ND6) gene. Initiation point mapping
      of the ND6 gene identified prominent free 5' ends of DNA, which are candidate
      start sites for DNA synthesis. Therefore we propose that the initiation zone of
      G. gallus mitochondrial DNA encompasses most, if not all, of the genome, with
      preferred initiation sites in regions flanking the major non-coding region.
      Comparison with mammals suggests a common mechanism of initiation of
      mitochondrial DNA replication in higher vertebrates.

PMID- 15557284
TI  - Novel algorithm for automated genotyping of microsatellites.
AB  - Microsatellites or short tandem repeats (STRs) are abundant in the human genome
      with easily assayed polymorphisms, providing powerful genetic tools for mapping
      both Mendelian and complex traits. Microsatellite genotyping requires detection
      of the products of polymerase chain reaction (PCR) amplification by
      electrophoresis, and analysis of the peak data for discrimination of the true
      allele. A high-throughput genotyping approach requires computer-based automation
      at both the detection and analysis phases. In order to achieve this, complicated
      peak patterns from individual alleles must be interpreted in order to assign
      alleles. Previous methods consider limited types of noise peaks and cannot
      provide enough accuracy. By pattern recognition of various types of noise peaks,
      such as stutter peaks and additional peaks, we have achieved an overall average
      accuracy of 94% for allele calling in our actual data. Our algorithm is crucial
      for a high-throughput genotyping system for microsatellite markers by reducing
      manual editing and human errors.

PMID- 15557285
TI  - Effects of polyamines on the muscarinic receptor-operated cation current in
      guinea-pig ileal smooth muscle myocytes.
AB  - The effects of extracellular and intracellular polyamines (PAs), spermine and
      putrescine, on the cation current (mI(CAT)) evoked either by activating
      muscarinic receptors with carbachol or by intracellularly applied GTPgammaS (in
      the absence of carbachol) were studied using patch-clamp recording techniques in
      single guinea-pig ileal myocytes. Extracellular spermine and putrescine rapidly
      and reversibly inhibited mI(CAT) in a concentration- and voltage-dependent manner
      with the IC(50) values at -40 mV of about 1 and 5 mM, respectively. Membrane
      depolarization relieved the blocking action of PAs although cation conductance
      activation curve remained N-shaped. The inhibition was similar for both carbachol
      and GTPgammaS-evoked currents, suggesting that the cation channel rather than
      the muscarinic receptor was the primary site of the PA action. In outside-out
      membrane patches, both cation channel unitary conductance and open probability
      were reduced. In perforated-patch experiments used to retain cytoplasmic PAs
      sustained 100 microM carbachol-induced mI(CAT) was significantly smaller (478 +/-
      76 pA, n = 7) compared to that recorded using conventional whole-cell
      configuration with nominally PA-free pipette solution (1314 +/- 76 pA, n = 12),
      but comparable in size to mI(CAT) with 0.3 mM spermine in the pipette solution
      (509 +/- 41 pA, n = 19). Intracellular putrescine inhibited mI(CAT) less potently
      compared to spermine. In conclusion, these results show a novel role of
      intestinal PAs in mI(CAT) inhibition, which can contribute to their well-known
      suppressing effect on the gastrointestinal smooth muscle excitability and
      contractility.

PMID- 15557286
TI  - Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA
      treatment.
AB  - Previously, we reported that H-2',6'-dimethyltyrosine [Dmt(1)]-d-Arg-Phe-Lys
      NH(2) (DALDA), an analogue of the naturally occurring opioid peptide dermorphin,
      is a highly potent and selective mu receptor agonist with low cross-tolerance to
      morphine. In the present study, we investigated the effect of treating mice
      chronically with [Dmt(1)]DALDA. The AD(50) of [Dmt(1)]DALDA (s.c.) increased
      eight-fold in animals given this drug chronically; in contrast, the AD(50)
      increased two-fold in mice chronically treated with morphine. The AD(50) of
      morphine (s.c.) in these [Dmt(1)]DALDA-treated animals was increased more than
      120 times, while that of the more selective mu agonist [d-Ala(2)-MePhe(4)-Gly
      ol(5)]enkephalin (DAMGO) given intrathecally was increased more than 240 times.
      However, the AD(50) of DAMGO given intracerebroventricularly was essentially the
      same in animals treated chronically with [Dmt(1)]DALDA as in naive animals. The
      dose of naloxone required to precipitate withdrawal in [Dmt(1)]DALDA-treated
      animals was 20 times lower than that in morphine-tolerant animals. Using real
      time quantitative PCR, we found that expression of the mu opioid receptor, delta
      opioid receptor, preproenkephalin and preprodynorphin genes was upregulated in
      the brain by [Dmt(1)]DALDA treatment. No significant changes in expression of
      opioid receptor or opioid peptide genes were detected in the spinal cord of
      [Dmt(1)]DALDA-treated mice, nor in the brain or spinal cord of morphine-treated
      mice. We conclude that a high degree of tolerance to [Dmt(1)]DALDA develops in
      the spinal cord but not brain, and cannot be accounted for by changes in
      expression of opioid receptors or opioid peptides in these tissues.

PMID- 15557287
TI  - Cyclic AMP-mediated inhibition of gallbladder contractility: role of K+ channel
      activation and Ca2+ signaling.
AB  - We have examined the mechanisms of cAMP-induced gallbladder relaxation by
      recording isometric tension and membrane potential in the intact tissue, and
      global intracellular calcium concentrations ([Ca(2+)](i)) and F-actin content in
      isolated myocytes. Both the phosphodiesterase (PDE) inhibitor, IBMX (100 microM)
      and the adenylate cyclase activator, forskolin (2 microM) caused decreases in
      basal tone that exhibited similar kinetics. IBMX and forskolin both caused
      concentration dependent, right-downward shifts in the concentration-response
      curves of KCl and cholecystokinin (CCK). IBMX and forskolin elicited a membrane
      hyperpolarization that was almost completely inhibited by the ATP-sensitive K(+)
      channel (K(ATP)) channel blocker, glibenclamide (10 microM). IBMX also induced an
      increase in large-conductance Ca(2+)-dependent K(+) (BK) channel currents,
      although the simultaneous blockade of BK and K(ATP) channels did not block IBMX-
      and forskolin-induced relaxations. Ca(2+) influx activated by L-type Ca(2+)
      channel activation or store depletion was also impaired by IBMX and forskolin,
      indicating a general impairment in Ca(2+) entry mechanisms. IBMX also decreases
      [Ca(2+)](i) transients activated by CCK and 3,6-Di-O-Bt-IP(4)-PM, a membrane
      permeable analog of inositol triphosphate, indicating an impairment in Ca(2+)
      release through IP(3) receptors. Ionomycin-induced [Ca(2+)](i) transients were
      not altered by IBMX, but the contractile effects of the Ca(2+) ionophore were
      reduced in the presence of IBMX, suggesting that cAMP can decrease Ca(2+)
      sensitivity of the contractile apparatus. A depolymerization of the thin filament
      could be reason for this change, as forskolin induced a decrease in F-actin
      content. In conclusion, these findings suggest that multiple, redundant
      intracellular processes are affected by cAMP to induce gallbladder relaxation.

PMID- 15557288
TI  - Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in
      horse penile small arteries.
AB  - The distribution of neuropeptide Y (NPY)-immunorective nerves and the receptors
      involved in the effects of NPY upon electrical field stimulation (EFS)- and
      noradrenaline (NA)-elicited contractions were investigated in horse penile small
      arteries. NPY-immunoreactive nerves were widely distributed in the erectile
      tissues with a particularly high density around penile intracavernous small
      arteries. In small arteries isolated from the proximal part of the corpora
      cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions
      elicited by both EFS and NA. At the same concentration, the NPY Y(1) receptor
      agonist, [Leu(31), Pro(34)]NPY, markedly potentiated responses to EFS and NA,
      whereas the NPY Y(2) receptor agonist, NPY(13-36), enhanced exogenous NA-induced
      contractions. In arteries precontracted with NA, NPY, peptide YY (PYY), [Leu(31),
      Pro(34)]NPY and the NPY Y(2) receptor agonists, N-acetyl[Leu(28,31)]NPY (24-36)
      and NPY(13-36), elicited concentration-dependent contractile responses. Human
      pancreatic polypeptide (hPP) evoked a biphasic response consisting of a
      relaxation followed by contraction. NPY(3-36), the compound 1229U91 (Ile-Glu-Pro
      Dapa-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic(2,4')diamide) and eventually NPY(13-36)
      relaxed penile small arteries. The selective NPY Y(1) receptor antagonist
      BIBP3226 ((R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]D-arginineamide)
      (0.3 microM) shifted to the right the concentration-response curves to both NPY
      and [Leu(31), Pro(34)]NPY and inhibited the contractions induced by the highest
      concentrations of hPP but not the relaxations observed at lower doses. In the
      presence of the selective NPY Y(2) receptor antagonist BIIE0246 ((S)-N2-[[1-[2-[4
      [(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-y1]-1-piperazinyl]-2
      oxoethyl]cyclo-pentyl-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2, 4
      triazol-4-yl]ethyl]-argininamide) (0.3 microM), the Y(2) receptor agonists NPY(13
      36) and N-acetyl[Leu(28,31)]NPY (24-36) evoked potent slow relaxations in NA
      precontracted arteries, under conditions of nitric oxide (NO) synthase blockade.
      Mechanical removal of the endothelium markedly enhanced contractions of NPY on NA
      precontracted arteries, whereas blockade of the neuronal voltage-dependent Ca(2+)
      channels did not alter NPY responses. These results demonstrate that NPY can
      elicit dual contractile/relaxing responses in penile small arteries through a
      heterogeneous population of postjunctional NPY receptors. Potentiation of the
      contractions evoked by NA involve both NPY Y(1) and NPY Y(2) receptors. An NO
      independent relaxation probably mediated by an atypical endothelial NPY receptor
      is also shown and unmasked in the presence of selective antagonists of the NPY
      contractile receptors.

PMID- 15557290
TI  - Phytic acid mobilization is an early response to chilling of the embryonic axes
      from dormant oilseed of hazel (Corylus avellana).
AB  - Dormancy of hazel (Corylus avellana L.) seeds is alleviated by a chilling
      treatment during which cytological, hormonal, and biochemical changes occur.
      Phytic acid and phosphate mobilization have been examined during this treatment.
      Phytic acid accounted for 0.7% and up to 3.2% of dry weight in axiferous and
      cotyledonary tissue, respectively. Phytic acid levels in embryonic axes were
      reduced by 60% within the first 3 weeks of chilling, with little subsequent
      change, in contrast to warm-imbibed tissue where levels did not change
      significantly. In cotyledons, phytic acid was mobilized to a lesser extent.
      Phosphate levels expressed on a fresh weight basis remained almost unaltered
      suggesting either the operation of a homeostatic mechanism for intracellular
      concentration or rapid utilization due to active metabolism. Phytase activity
      increased during stratification in both axiferous and cotyledonary tissue. The
      initial rise observed was associated with dormancy alleviation, since it occurred
      before the realization of full germination potential by the seeds and not in warm
      imbibed tissue. Protein bodies were isolated from hazel seeds by non-aqueous
      density gradients. Phytase activity was closely associated with the purified
      organelles, where phytic acid was located by light microscopy. Overall, these
      findings suggest that phytic acid mobilization by phytase and previously
      described processes associated with protein bodies, such as considerable
      proteolysis, are early participants in the plethora of events leading to seed
      dormancy relief and germination in hazel.

PMID- 15557291
TI  - Reduction of cell size induced by enod40 in Arabidopsis thaliana.
AB  - An extensive analysis of organ and cell size was performed in three different
      Arabidopsis lines transformed with the early nodulin gene enod40 under control of
      the CaMV35S promoter. All three transgenic lines presented a significant decrease
      in the mean size of both epidermal internode and leaf mesophyll cells. Flow
      cytometric and image analysis of enod40-transfected protoplasts prepared from
      wild-type Arabidopsis cell suspensions showed that transient expression of the
      gene resulted in reduced forward light scattering (a factor correlated with
      particle size) and cell size. The direct administration of ENOD40 peptide to
      fresh protoplasts also resulted in reduced forward scattering with respect to the
      control and to the administration of unrelated peptides. As far as is known this
      is the first report documenting a biological effect of enod40 at the cellular
      level in non-legume plants.

PMID- 15557292
TI  - Grafting raises the salt tolerance of tomato through limiting the transport of
      sodium and chloride to the shoot.
AB  - With the aim of determining whether grafting could improve salinity tolerance of
      tomato (Lycopersicon esculentum Mill.), and what characteristics of the rootstock
      were required to increase the salt tolerance of the shoot, a commercial tomato
      hybrid (cv. Jaguar) was grafted onto the roots of several tomato genotypes with
      different potentials to exclude saline ions. The rootstock effect was assessed by
      growing plants at different NaCl concentrations (0, 25, 50, and 75 mM NaCl) under
      greenhouse conditions, and by determining the fruit yield and the leaf
      physiological changes induced by the rootstock after 60 d and 90 d of salt
      treatment. The grafting process itself did not affect the fruit yield, as non
      grafted plants of cv. Jaguar and those grafted onto their own root showed the
      same yield over time under non-saline conditions. However, grafting raised fruit
      yield in Jaguar on most rootstocks, although the positive effect induced by the
      rootstock was lower at 25 mM NaCl than at 50 and 75 mM NaCl. At these higher
      levels, the plants grafted onto Radja, Pera and the hybrid VolgogradskijxPera
      increased their yields by approximately 80%, with respect to the Jaguar plants.
      The tolerance induced by the rootstock in the shoot was related to ionic rather
      than osmotic stress caused by salinity, as the differential fruit yield responses
      among graft combinations were mainly related to the different abilities of
      rootstocks to regulate the transport of saline ions. This was corroborated by the
      high negative correlation found between fruit yield and the leaf Na(+) or Cl(-)
      concentrations in salt-treated plants after 90 d of salt treatment. In
      conclusion, grafting provides an alternative way to enhance salt tolerance,
      determined as fruit yield, in the tomato, and evidence is reported that the
      rootstock is able to reduce ionic stress.

PMID- 15557293
TI  - The repair of double-strand breaks in plants: mechanisms and consequences for
      genome evolution.
AB  - The efficient repair of double-strand breaks (DSBs) in genomic DNA is important
      for the survival of all organisms. In recent years, basic mechanisms of DSB
      repair in somatic plant cells have been elucidated. DSBs are mainly repaired by
      non-homologous end-joining (NHEJ). The repair can be associated with deletions,
      but also insertions due to copying genomic sequences from elsewhere into the
      break. Species-specific differences of NHEJ have been reported and an inverse
      correlation of deletion size to genome size has been postulated, indicating that
      NHEJ might contribute significantly to evolution of genome size. DSB repair by
      homologous recombination (HR) might also influence genome organization. Whereas
      homology present in an allelic or an ectopic position is hardly used for repair,
      the use of homologous sequences in close proximity to the break is frequent. A
      'single-strand annealing' mechanism that leads to sequence deletions between
      direct repeats is particularly efficient. This might explain the accumulation of
      single long terminal repeats of retroelements in cereal genomes. The conservative
      'synthesis-dependent strand annealing' mechanism, resulting in conversions
      without crossovers is also prominent and seems to be significant for the
      evolution of tandemly arranged gene families such as resistance genes. Induction
      of DSBs could be used as a means for the controlled manipulation of plant genomes
      in an analogous way for the use of marker gene excision and site-specific
      integration.

PMID- 15557294
TI  - Involvement of the thylakoidal NADH-plastoquinone-oxidoreductase complex in the
      early responses to ozone exposure of barley (Hordeum vulgare L.) seedlings.
AB  - A possible implication of the plastid NADH-plastoquinone-oxidoreductase (Ndh)
      complex in the response against ozone-mediated oxidative stress in barley
      (Hordeum vulgare L.) leaves was investigated. After a 4 h treatment, exposure of
      barley seedlings to moderate ozone concentrations produced leaf-age-dependent
      increases in lipid peroxidation, peroxidase, and Ndh complex activities in the
      thylakoid membranes. A significant amount and activity of the Ndh complex were
      detected in mature barley leaves, but not in young barley leaves. In fact, young
      barley leaves behaved like ndh-deficient leaves in most of the aspects studied.
      When plants were exposed to photo-oxidative light after ozone fumigation, the
      recovery of Fv/Fm was lower in young leaves than in mature leaves. Ozone
      treatment significantly decreased non-photochemical quenching (qN) in young
      leaves, but not in mature leaves. Mature leaves showed higher levels of the
      energy (DeltamuH+) dependent (qE) component of qN. Treatment with antimycin A, an
      inhibitor of cyclic electron flow, increased the decay of qN produced by ozone in
      young leaves, but not in mature ones. The reduction state of plastoquinone
      increased after ozone treatment in mature dark-adapted leaves and was strongly
      quenched by far red light. It is proposed that the function of the Ndh complex
      helps the maintenance of qN, probably through the poising of the redox steady
      state level of the intersystem carriers and then by optimizing the rate of cyclic
      electron flow. This should constitute an age-dependent early response in barley
      leaves, by contributing to minimize photoinhibition in the presence of ozone and
      high light.

PMID- 15557295
TI  - Molecular design of the photosystem II light-harvesting antenna: photosynthesis
      and photoprotection.
AB  - The photosystem II (PSII) light-harvesting system carries out two essential
      functions, the efficient collection of light energy for photosynthesis, and the
      regulated dissipation of excitation energy in excess of that which can be used.
      This dual function requires structural and functional flexibility, in which light
      harvesting proteins respond to an external signal, the thylakoid DeltapH, to
      induce feedback control. This process, referred to as non-photochemical quenching
      (NPQ) depends upon the xanthophyll cycle and the PsbS protein. In nature, NPQ is
      heterogeneous in terms of kinetics and capacity, and this adapts photosynthetic
      systems to the specific dynamic features of the light environment. The molecular
      features of the thylakoid membrane which may enable this flexibility and
      plasticity are discussed.

PMID- 15557296
TI  - Azetidine-induced accumulation of class I small heat shock proteins in the
      soluble fraction provides thermotolerance in soybean seedlings.
AB  - Accumulation of class I small heat shock proteins (sHSPs) is induced by the
      proline analog, azetidine-2-carboxylic acid (Aze) in soybean seedlings to a level
      similar to that induced by exposure to 40 degrees C. However, only the treatment
      with 10 mM Aze for 6 h and subsequently with 10 mM proline for 24 h protected the
      seedlings from damage during subsequent exposure to 45 degrees C as assessed by
      2,3,5-triphenyltetrazolium chloride (TTC) staining. A chaperone activity assay
      showed that the purified class I sHSPs induced by Aze were functional in vitro
      and protected proteins from thermal denaturation. Amino acid composition analysis
      indicated that Aze was not incorporated into de novo synthesized class I sHSPs.
      Accumulation of class I sHSPs in the soluble post-ribosomal supernatant fraction
      was found to be important for acquisition of thermotolerance. We suggest that
      both the accumulation of class I sHSPs and their presence in the soluble fraction
      are important for establishment of thermotolerance.

PMID- 15557297
TI  - Whither (wither?) the ultrasound specialist?

PMID- 15557298
TI  - Intraoperative ultrasonography of the liver in patients with abdominal tumors: a
      new approach.
AB  - OBJECTIVES: To compare liver intraoperative ultrasonography (IOU), computed
      tomography (CT), preoperative ultrasonography (USG), and intraoperative
      inspection and palpation in the detection of hepatic lesions in patients with
      abdominal tumors. METHODS: This was a prospective study including 60 patients
      with abdominal tumors evaluated by USG, CT, inspection and palpation, and hepatic
      IOU during exploratory laparotomy. Sensitivity, specificity, and positive and
      negative predictive values for all methods were calculated. Agreement of methods
      with histopathologic results was calculated by kappa statistics and the Spearman
      coefficient. RESULTS: Of the 60 patients, 49 (81.6%) had positive findings for
      hepatic lesions. Lesions could not be counted in 3 patients. The 46 remaining
      cases were diagnosed by histologic examination. Sensitivity, specificity, and
      positive and negative predictive values were 42.9%, 88.9%, 90%, and 40% for USG;
      59.5%, 77.8%, 86.2%, and 45.2% for CT; 69.0%, 88.9%, 93.5%, and 55.2% for
      inspection and palpation; and 90.5%, 77.8%, 90.5%, and 77.8% for IOU, with
      histologic examination used as a criterion standard. Fair to moderate agreement
      was found for USG, CT, and inspection and palpation (kappa = 0.24, 0.31, and
      0.49, respectively). Substantial agreement was found for IOU (kappa = 0.68).
      Changes in surgical strategy were made in 19 (41.3%) of the 46 cases with
      positive findings. CONCLUSIONS: High sensitivity associated with substantial
      agreement with histopathologic findings shows that IOU is an indispensable
      evaluation method for hepatic screening in patients with abdominal tumors who
      undergo laparotomy and should become a routine procedure wherever available.

PMID- 15557299
TI  - Real-time imaging with the sonographic contrast agent SonoVue: differentiation
      between benign and malignant hepatic lesions.
AB  - OBJECTIVE: We investigated the ability of contrast-enhanced sonography with
      SonoVue (Altana Pharma, Konstanz, Germany), a sulfur hexafluoride microbubble
      contrast agent, to reveal differences between benign and malignant focal hepatic
      lesions. METHODS: One hundred twenty-six lesions in 124 patients with focal
      hepatic lesions detected by B-mode sonography (hepatocellular carcinoma, n = 36;
      metastasis, n = 25; cholangiocellular carcinoma, n = 1; lymphoma, n = 2; focal
      nodular hyperplasia, n = 9; adenoma, n = 4; regenerative cirrhotic nodule, n =
      13; hemangioma, n = 29; and focal hyposteatosis, n = 7) were examined in a
      prospective study. After intravenous injection of 2.4 mL of SonoVue, the liver
      was examined continuously for 3 minutes by low-mechanical index pulse inversion
      sonography. RESULTS: For the discrimination of malignant versus benign liver
      lesions, SonoVue-enhanced sonography improved sensitivity from 78% to 100% and
      specificity from 23% to 92% compared with baseline sonography. Receiver operating
      characteristic analysis revealed a significant improvement in this discrimination
      (area under the receiver operating characteristic curve, 0.510 +/- 0.054 [SD] at
      baseline sonography, 0.998 +/- 0.003 with SonoVue-enhanced sonography; P < .001).
      The following flow patterns in the early phase were diagnosis specific: early
      central starlike pattern for focal nodular hyperplasia, peripheral globular
      nodular pattern for hemangioma, and diffuse arterial enhancement for malignant
      lesions. Homogeneous enhancement in the late phase was predictive for benign
      lesions (P < .001). Conversely, 93% of patients without contrast enhancement in
      the late phase had malignant lesions (P < .001). CONCLUSIONS: SonoVue-enhanced
      sonography has greater specificity and sensitivity than baseline sonography for
      the differentiation of benign and malignant liver lesions.

PMID- 15557300
TI  - Bioeffects of low-frequency ultrasonic gene delivery and safety on cell membrane
      permeability control.
AB  - OBJECTIVE: To develop a novel method of ultrasonic naked gene delivery (UNGD); to
      examine the relationship between optimal parameters of ultrasound exposure and
      cell membrane permeability, enzymes, and free radicals; and to find optimal
      control parameters that were realizable, reliable, and noncytotoxic for use in
      gene therapy. METHODS: Suspensions of chicken, rabbit, and rat red blood cells
      and S180 cells were exposed to a calibrated ultrasonic field with different
      parameters in both the still and flowing states to obtain optimal parameters for
      UNGD. The optimal parameters then were used to implement UNGD. We examined
      morphologic characteristics, membrane permeability, enzymes, free radicals, naked
      gene expression efficiency, cell damage threshold, and cell viability by laser
      scanning confocal microscopy, fluorescent microscopy, flow cytometry, and
      spectrophotometry. RESULTS: Green fluorescent protein (GFP) as a reporter was
      delivered into S180 cells under the optimal parameters without cell damage or
      cytotoxicity. The transfection rate (mean +/- SD) was approximately 35.83% +/-
      2.53% (n = 6) in viable cells, and cell viability was 90.17% +/- 1.47% (n = 6).
      The intensity of GFP expression with UNGD showed a higher fluorescent peak over
      both an adeno-associated virus vector-GFP group and a control group (P < .001).
      Additionally, malondialdehyde, hydroxyl free radicals, alkaline phosphatase, and
      acid phosphatase displayed an S-shaped growth model (r = 0.98 +/- 0.01) in
      response to permeability and morphologic alteration. CONCLUSIONS: Under optimal
      conditions, low-frequency ultrasound can safely deliver naked genes into cells
      without causing cell damage. The analytical results indicate that, except for
      subcavitation, free radical products are responsible for bioeffects in gene
      delivery. The constant E of energy deposition at 90% cell viability is the
      optimal control factor, and 80% viability represents the damage threshold.
      Optimal gene uptake by cells and safety depend on E. Constant E can be applied to
      control the gene delivery effect in combination with other parameters.

PMID- 15557301
TI  - Reevaluation of ultrasonography for solid-organ injury in blunt abdominal trauma.
AB  - OBJECTIVE: To reevaluate the usefulness of ultrasonography for detecting and
      classifying solid-organ injuries from blunt abdominal trauma by comparing
      ultrasonography with computed tomography (CT) and laparotomy. METHODS: Six
      hundred four patients with blunt abdominal trauma were examined by both B-mode
      ultrasonography and CT for a study period of 14 years. The ultrasonographic
      examiners were divided into 2 groups depending on their experience with
      ultrasonography. The ultrasonographic results were then compared with CT and
      surgical findings. This was a retrospective study. RESULTS: In 198 patients,
      solid-organ injuries were identified on CT, laparotomy, or both. Sensitivity
      values in group A (experts) were 87.5% for hepatic injuries, 85.4% for splenic
      injuries, 77.6% for renal injuries, and 44.4% for pancreatic injuries.
      Sensitivity values in group B were 46.2% for hepatic injuries, 50.0% for splenic
      injuries, and 44.1% for renal injuries. The detection rates in group A were 80%
      to 100% for different types of hepatic injuries except superficial injuries (20%)
      and 70% to 100% for different types of splenic injuries. The detection rates for
      renal parenchymal and pancreatic duct injuries were 53.3% and 80%, respectively.
      The detection rates for injuries requiring intervention were 86.1% in group A and
      66.7% in group B. CONCLUSIONS: The sensitivity of ultrasonography with the use of
      CT and surgical findings as reference standards decreased compared with our prior
      study. However, ultrasonography was found to enable experienced examiners to
      detect and classify parenchymal injuries efficiently, despite disadvantages in
      detecting superficial and vascular injuries. Ultrasonography should be used to
      explore not only free fluid but also solid-organ injuries.

PMID- 15557302
TI  - Characterization of a linear streak artifact with pulse inversion tissue
      harmonics in musculoskeletal sonography.
AB  - OBJECTIVE: To understand a linear artifact that projects deep to reflective
      structures that move rapidly while using tissue harmonic imaging with pulse
      inversion (PI) sonography. We hypothesize that this artifact is due to a
      cancellation error between firings in PI imaging, and it is, therefore, similar
      in generation to the twinkling artifact in color Doppler sonography. This
      artifact could be studied with the use of surfaces of different roughness to
      represent different rates of motion, in which roughness corresponds to spatial
      fluctuations in surface height. Given very slight variations in beam focusing as
      occurs with sonographic imaging arrays, these spatial fluctuations translate into
      temporal fluctuations in the received signal as would occur with tissue motion.
      METHODS: We scanned 4 different sandpaper grits and a smooth surface through a
      water path using fundamental and PI mode, 1- and 2-pulse techniques,
      respectively. The sandpaper and the smooth surface were scanned through a water
      path at mechanical indices of 0.1 to 0.7. Four independent images were subtracted
      pairwise to remove nonfluctuating signals. These noise pixels were counted and
      analyzed. RESULTS: Analysis of variance showed that the noise generated behind
      the different surfaces was highly significantly different. Two-tailed t tests
      generally showed significant differences in the quantity of noise between
      fundamental and harmonic imaging behind the roughest 3 grades of sandpaper. A
      multiple regression model showed significantly greater slopes for harmonic
      imaging for all grades of sandpaper and the smooth surface. CONCLUSIONS: The
      noise and, by extension, the linear streak artifact in musculoskeletal imaging
      are dependent on the mechanical index and are functions of sandpaper roughness.
      This would be equivalent to a subtraction error between 2 firings due to soft
      tissue motion, and the artifact may be a way to identify rapid soft tissue motion
      in PI images.

PMID- 15557303
TI  - Renal venous Doppler sonography in preeclampsia.
AB  - OBJECTIVE: The elevation in blood pressure associated with preeclampsia appears
      to be associated with a shift in the renal pressure natriuresis curve. Pressure
      natriuresis is modulated by renal medullary pressure. In obstructive uropathy,
      Doppler sonography has been used to indicate changes in renal venous impedance,
      possibly measuring alterations in medullary pressure and compliance in this
      condition. The hypothesis tested in this study was that an elevation in renal
      venous pulsation may occur in preeclampsia compared with normal pregnancy.
      METHODS: Seven patients with clinical evidence of preeclampsia were referred for
      fetal well-being confirmation by sonography in the third trimester. Seven
      pregnant patients without renal disease or hypertension reviewed in the third
      trimester served as a control group. Doppler studies of the interlobar arteries
      and veins of both kidneys were performed, with a total of 14 kidneys imaged per
      group. Arterial and venous impedance indices were obtained. The impedance indices
      for the patients were compared by the Student t test. RESULTS: No significant
      difference was noted between the arterial resistive indices. The mean venous
      impedance index for the hypertensive patients was 0.50 +/- 0.12, and that for the
      control patients was 0.37 +/- 0.06 (P = .003). CONCLUSIONS: Preeclampsia in the
      third trimester appears to be associated with altered medullary venous pulsation,
      possibly indicating reduced medullary pressure.

PMID- 15557304
TI  - Reproducibility of the fetal nasal bone length measurement.
AB  - OBJECTIVE: To investigate the reproducibility of the fetal nasal bone length
      measurement in the first trimester. METHODS: In this prospective study, crown
      rump length, nuchal translucency, and nasal bone length were measured in 90
      singleton pregnancies between 11 and 14 weeks of pregnancy. The study was divided
      into 2 equal substudies. Three investigators measured the nasal bone in study I.
      After an intensive 3-month training program, the same 3 investigators measured
      the nasal bone in study II. Measurement of the nasal bone was standardized. All
      investigators were blinded and measured the nasal bone 3 times. The intraclass
      correlation coefficient (intra-CC) and interclass correlation coefficient (inter
      CC) were calculated. RESULTS: Nasal bone length measurement was successfully
      performed in all cases. The median nasal bone lengths were 2.3 (range, 1.5-3.2),
      2.6 (range, 1.4-4.2), and 2.9 (range, 2.1-3.8) mm between 77 and 83, 84 and 90,
      and 91 and 98 days' gestational age, respectively; median crown-rump length was
      63.0 (range, 45.0-83.3) mm; and median nuchal translucency measurement was 1.3
      (range, 0.9-2.5) mm. The correlation between the 3 observers was poor (inter-CC,
      0.32) in the first study. After the training program, the interobserver
      correlation improved but was still moderate (inter-CC, 0.64). In both studies the
      interobserver variability did not differ between 11, 12, and 13 weeks'
      gestational age. There was no relationship between the mean nasal bone length and
      interobserver difference in both studies. The intraobserver variability was good
      for each investigator in both studies (intra-CC: study I, 0.93, 0.95, and 0.97;
      study II, 0.98, 0.97, and 0.97, respectively). CONCLUSIONS: This study shows that
      the reproducibility of the fetal nasal bone length measurement in the first
      trimester is inadequate.

PMID- 15557305
TI  - Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with
      Down syndrome: description by 3-dimensional ultrasonography and clinical
      significance.
AB  - OBJECTIVE: To determine the frequency and clinical significance of bilateral and
      unilateral hypoplastic nasal bones for the detection of Down syndrome by 3
      dimensional ultrasonography. METHODS: Thirty-seven volumes of the fetal skull
      from fetuses with Down syndrome and 37 from fetuses without abnormalities were
      analyzed by 1 investigator blinded to fetal karyotype. The maximum intensity
      projection algorithm was used to reconstruct nasal bones. Ossification patterns
      were identified in anteroposterior and profile views. Sensitivity, false-positive
      rates (FPRs), and likelihood ratios (LRs) for detection of Down syndrome were
      calculated. RESULTS: After exclusions (coronal acquisition [n = 11], hand in
      front of the face [n = 4], poor imaging [n = 2], incomplete follow-up [n = 2],
      and anomalies detected after delivery [n = 2]), 53 volumes were analyzed (26
      fetuses with Down syndrome and 27 without abnormalities; median gestational age,
      21 6/7 weeks [interquartile range, 19 6/7-25 2/7 weeks]). Rendered profile views
      revealed absent nasal bones in 18.9% (10 of 53) of the fetuses, and, among these,
      90% (9 of 10) had Down syndrome (sensitivity, 34.6% [9 of 26]; FPR, 3.7% [1 of
      27]; LR, 9.3 [95% confidence interval (CI), 1.3-68.7]). Three ossification
      patterns were identified in anteroposterior views: (1) normally developed, (2)
      delayed ossification, and (3) absent nasal bones. Sensitivity, FPR, and LR of
      absent nasal bones for detecting Down syndrome were 34.6% (9 of 26), 3.7% (1 of
      27), and 9.0 (95% CI, 1.3-68.7), respectively. Sensitivity, FPR, and LR of
      delayed ossification for detecting Down syndrome were 42.3% (11 of 26), 22% (6 of
      27), and 1.83 (95% CI, 0.8-4.4). CONCLUSIONS: Absence of nasal bones is
      associated with the highest risk of Down syndrome. Delayed ossification is
      associated with a lower risk of Down syndrome than absent nasal bones. These
      ossification patterns may be indistinguishable on 2-dimensional ultrasonography.

PMID- 15557306
TI  - Contrast-enhanced sonography helps in discrimination of benign from malignant
      adnexal masses.
AB  - OBJECTIVE: To investigate the potential efficacy of real-time contrast-enhanced
      power Doppler sonography in the differentiation of benign and malignant adnexal
      masses in a pilot study. METHODS: Before surgical treatment, adnexal masses were
      prospectively evaluated with power Doppler sonography before and after injection
      of a contrast agent. Real-time postinjection sequences were computerized with
      time-intensity analysis software to determine an enhancement curve and contrast
      parameters. The intraobserver and interobserver reproducibilities of these
      criteria were assessed on a subsample. These contrast parameters were compared
      between benign and malignant tumors using logistic regression. Sensitivity and
      specificity were used to compare contrast parameters with sonographic and Doppler
      variables. RESULTS: Ninety-nine women were included, for a total of 101 adnexal
      masses. There were 23 cases of ovarian malignancies and 78 benign adnexal
      lesions. Our procedure had excellent intraobserver and interobserver
      reproducibility, with an average intraclass correlation coefficient of 0.92. The
      time before enhancement and intensity ratio did not reliably differentiate
      between the benign and malignant masses. Washout times and areas under the curves
      were significantly greater in ovarian malignancies than in other benign tumors (P
      < .001), leading to sensitivity estimates between 96% and 100% and specificity
      estimates between 83 and 98%. Contrast parameters had slightly higher sensitivity
      and slightly lower specificity when compared with transvaginal sonographic
      variables of the resistive index and serum cancer antigen 125 levels.
      CONCLUSIONS: Contrast-enhanced power Doppler imaging may easily and precisely
      discriminate benign from malignant adnexal lesions. Larger studies are needed to
      determine the appropriate use and benefits of this new procedure.

PMID- 15557307
TI  - Sonographic whirlpool sign in ovarian torsion.
AB  - OBJECTIVE: To describe an additional maneuver during sonography for ovarian
      torsion and to assess its diagnostic value. METHODS: During a period of about 2
      years 6 months, 21 patients with acute or intermittent lower abdominal pain who
      had an ovarian mass and an extraovarian mass suggestive of a twisted vascular
      pedicle on sonography were studied. The gray scale features of the ovarian mass
      were recorded. The presence of a twisted vascular pedicle was evaluated. Its
      location and gray scale features were noted. The probe was moved to and fro along
      the axis of the pedicle, and the presence of a whirlpool sign was evaluated. The
      same procedure was repeated on a color Doppler study. RESULTS: A twisted pedicle
      with a whirlpool sign was seen in all 21 patients. Ovarian torsion was confirmed
      in all 20 patients who underwent surgery. The last patient was pregnant and did
      well with conservative treatment. Hemorrhagic infarction or early hemorrhage of
      the ovary or ovarian mass was seen in all 8 patients who did not show flow in the
      twisted pedicle on the color Doppler study and in 2 patients who showed flow in
      the artery in the proximal part of the pedicle. Of the 6 patients who showed flow
      in the artery alone, the ovary was removed in 4, and all had hemorrhagic
      infarction or early hemorrhage. The ovary was viable in all 5 patients in whom
      flow was seen in both the artery and vein. CONCLUSIONS: A positive whirlpool sign
      in the twisted vascular pedicle of the ovary is the most definitive sign of
      ovarian torsion. Absence of blood flow in the twisted pedicle and visualization
      of the flow in the artery alone are predictive of nonviability of the ovary.

PMID- 15557308
TI  - Short foot length: a diagnostic pointer for harlequin ichthyosis.
AB  - OBJECTIVE: Among the fetal skin disorders, harlequin ichthyosis is the one that
      has specific sonographic features in the antenatal period. A few cases of
      antenatal diagnosis of harlequin ichthyosis with typical facial features of
      ectropion and eclabium have been described. The manifestation of the phenotype is
      usually in the third trimester. Fetal skin biopsy can be done in the late second
      trimester for diagnosing fetal skin disorders. We aimed to see whether a short
      foot length could be a pointer for the diagnosis of harlequin ichthyosis in the
      second trimester before the full phenotypic manifestation, which is usually seen
      in the third trimester. METHODS: We report 3 cases of harlequin ichthyosis, 2 of
      them diagnosed in the third trimester with abnormal facial features and another
      second-trimester sonographic diagnosis based on short foot length, without
      eclabium and ectropion. RESULTS: In all 3 cases, the foot length was considerably
      smaller than the femur length, especially in the third case, in which the foot
      length was smaller than the femur length before the manifestation of the typical
      features of harlequin ichthyosis. CONCLUSIONS: Fetal foot length may be an
      important and probably the first marker seen in the second trimester for the
      diagnosis of harlequin ichthyosis.

PMID- 15557309
TI  - Double intussusception in a child: the triple-circle sign.

PMID- 15557310
TI  - Successful sonographically guided laser ablation of a large acardiac twin at 26
      weeks' gestation.

PMID- 15557311
TI  - Popliteal artery entrapment syndrome in an elite rower: sonographic appearances.

PMID- 15557312
TI  - Iatrogenic pseudoaneurysm of the superior thyroid artery: color Doppler
      ultrasonographic diagnosis and treatment approach.

PMID- 15557313
TI  - Sonographic diagnosis and monitoring of an obstructing duodenal hematoma after
      blunt trauma: correlation with computed tomographic and surgical findings.

PMID- 15557314
TI  - Doppler sonography of renal obstruction.

PMID- 15557315
TI  - Anti-CD28-induced co-stimulation and TCR avidity regulates the differential
      effect of TGF-beta1 on CD4+ and CD8+ naive human T-cells.
AB  - TGF-beta1 is a powerful regulator of various T-cell functions. However, it has
      been unclear how the T-cell responsiveness towards TGF-beta1 is affected by its
      phenotype or signaling intensity. In the present study, we demonstrate that the
      phenotype and the TCR-signaling intensity of the responding T-cell as well as the
      presence of anti-CD28 co-stimulation markedly affects how naive human cord blood
      T-cells respond to TGF-beta1. In this report we demonstrate that the strength of
      the stimulatory signal modifies the T-cell response towards TGF-beta1. Thus, the
      greatest anti-proliferative effect of TGF-beta1 was observed during weak
      stimulatory conditions (low dose of anti-CD3 with no co-stimulatory signal).
      However, such anti-proliferative effect was reduced during strong stimulatory
      signal (high dose of anti-CD3 with a CD28-directed co-stimulatory signal). In
      addition, our results indicate that CD8+ T-cells are generally more responsive
      towards TGF-beta1 than CD4+ T-cells. To our surprise, naive T-cells had a skewed
      Th1/Tc1 cytokine secretion pattern with high amounts of IL-2, IFNgamma and
      TNFalpha, but low amounts of IL-4, IL-5 and IL-10. TGFbeta1 significantly reduced
      the secretion of IL-2 and IFNgamma, but such suppression was partially prevented
      by anti-CD28-induced co-stimulation. In contrast, the inhibitory effect on IL-5
      secretion was unaffected by anti-CD28 co-stimulation. Interestingly, TGF-beta1
      induced IL-10 and TNFalpha secretion. However, the induction of IL-10 secretion
      was reduced during optimal stimulatory conditions while TGF-beta1 further induced
      TNFalpha secretion. These data demonstrate that the duration, intensity and type
      of signaling alters the sensitivity of T-cells to powerful immunological
      modifying agents like TGF-beta1.

PMID- 15557316
TI  - Phenotypical and functional alterations in the mucosal immune system of CD45 exon
      9 KO mice.
AB  - The protein tyrosine phosphatase CD45 has been shown to be an important regulator
      of antigen-receptor signaling in both T and B lymphocytes. Lymphocyte populations
      within the gut mucosa are phenotypically and ontogenetically different from those
      generally found in secondary lymphoid tissue. In T lymphopenic mice, extrathymic
      T cell development takes place within the gut. Here we report the
      characterization of T and B cell populations in the distinct compartments of the
      gut mucosa and gut-associated lymphoid tissue of CD45-null mice. These data
      suggest that CD45 is required for the development of the specialized T cell
      populations within the gut environment as has been previously shown for thymic
      development. We demonstrate that within the large intestine intraepithelial
      compartment alphabeta-TCR+ CD4+ T cells are selectively retained by CD45KO mice.
      T cells and NK cells within the intraepithelium and the gut mucosa associated
      lymphoid tissue of CD45KO mice frequently possess an activated phenotype,
      differentiated to produce typical TH1 and TH2 cytokines. These data demonstrate
      that local environmental differences within the gut can, at least in part,
      overcome the requirement for CD45 during activation of T cells.

PMID- 15557318
TI  - Promiscuity in the geometry of electrostatic interactions between the Escherichia
      coli multidrug resistance transporter MdfA and cationic substrates.
AB  - The Escherichia coli multidrug transporter MdfA contains a single membrane
      embedded charged residue (Glu-26) that plays a critical role in the recognition
      of cationic substrates (Edgar, R., and Bibi, E. (1999) EMBO J. 18, 822-832).
      Using an inactive mutant (MdfA-E26T), we isolated a spontaneous second-site
      mutation (MdfA-E26T/V335E) that re-established the recognition of cationic drugs
      by the transporter. Only a negative charge at position 335 was able to restore
      the functioning of the inactive mutant MdfA-E26T. Intriguingly, the two
      genetically interacting residues are located at remote and distinct regions along
      the secondary structure of MdfA. Glu-26 is located in the periplasmic half of
      transmembrane helix 1, and as shown here, the complementing charge at position
      335 resides within the cytoplasmic loop connecting transmembrane helices 10 and
      11. The spatial relation between the two residues was investigated by cross
      linking. A functional split version of MdfA devoid of cysteines was constructed
      and introduced with a cysteine pair at positions 26 and 335. Strikingly, the
      results indicate that residues 26 and 335 are spatially adjacent, suggesting that
      they both constitute parts of the multidrug recognition pocket of MdfA. The fact
      that electrostatic interactions are preserved with cationic substrates even if
      the critical acidic residue is placed on another face of the pocket reveals an
      additional dimension of promiscuity in multidrug recognition and transport.

PMID- 15557319
TI  - Kinetic analysis of the individual steps of protein splicing for the Pyrococcus
      abyssi PolII intein.
AB  - Protein splicing involves the excision of an intervening polypeptide, the intein,
      from flanking polypeptides, the exteins, concomitant with the specific ligation
      of the exteins. The intein that interrupts the DNA polymerase II DP2 subunit in
      Pyrococcus abyssi can be overexpressed and purified as an unspliced precursor,
      which allows for a detailed in vitro kinetic analysis of the individual steps of
      protein splicing. The first order rate constant for splicing of this intein,
      which has a non-canonical Gln at its C terminus, is 9.3 x 10(-6) s(-1) at 60
      degrees C. The rate constant for splicing increases 3-fold with substitution of
      Asn for the C-terminal Gln. The pseudo first order rate constant of
      dithiothreitol-dependent N-terminal cleavage is 1 x 10(-4) s(-1). The first order
      rate constant of C-terminal cleavage is 1.2 x 10(-5) s(-1) with Gln at the C
      terminal position, 2.8 x 10(-4) s(-1) with Asn, and decreases significantly with
      mutation of the penultimate His of the intein to Ala. N-terminal cleavage is most
      efficient between pH 7 and 7.5 and decreases at both more acidic and alkaline pH
      values, whereas C-terminal cleavage and splicing are both efficient over a
      broader range of pH values.

PMID- 15557320
TI  - Evidence that monoclonal antibodies directed against the integrin beta subunit
      plexin/semaphorin/integrin domain stimulate function by inducing receptor
      extension.
AB  - The overall structure of integrins is that of a ligand-binding head connected to
      two long legs. The legs can exhibit a pronounced bend at the "knees," and it has
      been proposed that the legs undergo a dramatic straightening when integrins
      transit from a low affinity to a high affinity state. The knee region contains
      domains from both alpha and beta subunits, including the N-terminal
      plexin/semaphorin/integrin (PSI) domain of the beta subunit. The role played by
      the knee domains in the regulation of integrin-ligand binding is uncertain. Here
      we show that: (i) monoclonal antibodies (mAbs) N29 and 8E3 have epitopes in the
      beta(1) subunit PSI domain and stimulate ligand binding to alpha(5)beta(1); (ii)
      N29 and 8E3 cause long range conformational changes that alter the ligand binding
      activity of the head region; (iii) the stimulatory action of these mAbs is
      dependent on the calf-1 domain, which forms part of the alpha subunit knee; and
      (iv) the epitopes of 8E3 and N29 map close to the extreme N terminus of the PSI
      and are likely to lie on the side of this domain that faces the alpha subunit.
      Taken together, our data suggest that the binding of these mAbs results in a
      levering apart of the PSI and calf-1 domains, and thereby causes the alpha and
      beta subunit knees to separate. Several major inferences can be drawn from our
      findings. First, the PSI domain appears to form part of an interface with the
      alpha subunit that normally restrains the integrin in a bent state. Second, the
      PSI domain is important for the transduction of conformational changes from the
      knee to head. Third, unbending is likely to provide a general mechanism for
      control of integrin-ligand recognition.

PMID- 15557321
TI  - Mechanism of uptake and incorporation of the non-human sialic acid N
      glycolylneuraminic acid into human cells.
AB  - N-Glycolylneuraminic acid (Neu5Gc) is a widely expressed sialic acid in mammalian
      cells. Although humans are genetically deficient in producing Neu5Gc, small
      amounts are present in human cells in vivo. A dietary origin was suggested by
      human volunteer studies and by observing that free Neu5Gc is metabolically
      incorporated into cultured human carcinoma cells by unknown mechanisms. We now
      show that free Neu5Gc uptake also occurs in other human and mammalian cells.
      Inhibitors of certain non-clathrin-mediated endocytic pathways reduce Neu5Gc
      accumulation. Studies with human mutant cells show that the lysosomal sialic acid
      transporter is required for metabolic incorporation of free Neu5Gc. Incorporation
      of glycosidically bound Neu5Gc from exogenous glycoconjugates (relevant to human
      gut epithelial exposure to dietary Neu5Gc) requires the transporter as well as
      the lysosomal sialidase, which presumably acts to release free Neu5Gc. Thus,
      exogenous Neu5Gc reaches lysosomes via pinocytic/endocytic pathways and is
      exported in free form into the cytosol, becoming available for activation and
      transfer to glycoconjugates. In contrast, N-glycolylmannosamine (ManNGc)
      apparently traverses the plasma membrane by passive diffusion and becomes
      available for conversion to Neu5Gc in the cytosol. This mechanism can also
      explain the metabolic incorporation of chemically synthesized unnatural sialic
      acids, as reported by others. Finally, to our knowledge, this is the first
      example of delivery to the cytosol of an extracellular small molecule that cannot
      cross the plasma membrane, utilizing fluid pinocytosis and a specific lysosomal
      transporter. The approach could, thus, potentially be generalized to any small
      molecule that has a specific lysosomal transporter but not a plasma membrane
      transporter.

PMID- 15557322
TI  - UTP induces osteopontin expression through a coordinate action of NFkappaB,
      activator protein-1, and upstream stimulatory factor in arterial smooth muscle
      cells.
AB  - Osteopontin (OPN) is an important chemokinetic agent for several cell types. Our
      earlier studies have shown that its expression is essential for uridine
      triphosphate (UTP)-mediated migration of vascular smooth muscle cells. We
      demonstrated previously that the activation of an AP-1 binding site located 76 bp
      upstream of the transcription start in the rat OPN promoter is involved in the
      induction of OPN expression. In this work, using a luciferase promoter deletion
      assay, we identified a new region of the rat OPN promoter (-1837 to -1757) that
      is responsive to UTP. This region contains an NFkappaB site located at -1800 and
      an Ebox located at -1768. Supershift electrophoretic mobility shift assay and
      chromatin immunoprecipitation assays identified NFkappaB and USF-1/USF-2 as the
      DNA binding proteins induced by UTP, respectively, for these two sites. Using
      dominant negative mutants of IkappaB kinase and USF transcription factors, we
      confirmed that NFkappaB and USF-1/USF-2 are involved in the UTP-mediated
      expression of OPN. Using a pharmacological approach, we demonstrated that USF
      proteins are regulated by the extracellular signal-regulated kinase (ERK)1/2
      pathway, just as the earlier discovered AP-1 complex, whereas NFkappaB is up
      regulated through PKCdelta signals. Finally, our work suggests that the UTP
      stimulated OPN expression involves a coordinate regulation of PKCdelta-NFkappaB,
      ERK1/2-USF, and ERK1/2/NAD(P)H oxidase AP-1 signaling pathways.

PMID- 15557323
TI  - Crystal structure of the bovine mitochondrial elongation factor Tu.Ts complex.
AB  - The three-dimensional structure of the bovine mitochondrial elongation factor
      (EF)-Tu.Ts complex (EF-Tumt.Tsmt) has been determined to 2.2-A resolution using
      the multi-wavelength anomalous dispersion experimental method. This complex
      provides the first insight into the structure of EF-Tsmt. EF-Tsmt is similar to
      Escherichia coli and Thermus thermophilus EF-Ts in the amino-terminal domain.
      However, the structure of EF-Tsmt deviates considerably in the core domain with a
      five-stranded beta-sheet forming a portion of subdomain N of the core. In E. coli
      EF-Ts, this region is composed of a three-stranded sheet. The coiled-coil domain
      of the E. coli EF-Ts is largely eroded in EF-Tsmt, in which it consists of a
      large loop packed against subdomain C of the core. The conformation of bovine EF
      Tumt in complex with EF-Tsmt is distinct from its conformation in the EF-Tumt.GDP
      complex. When domain III of bovine EF-Tumt.GDP is superimposed on domain III of
      EF-Tumt in the EF-Tumt.Tsmt complex, helix B from domain I is also almost
      superimposed. However, the rest of domain I is rotated relative to this helix
      toward domain II, which itself is rotated toward domain I relative to domain III.
      Extensive contacts are observed between the amino-terminal domain of EF-Tsmt and
      domain I of EF-Tumt. Furthermore, the conserved TDFV sequence of EF-Tsmt also
      contacts domain I with the side chain of Asp139 contacting helix B of EF-Tumt and
      inserting the side chain of Phe140 between helices B and C. The structure of the
      EF-Tumt.Tsmt complex provides new insights into the nucleotide exchange mechanism
      and provides a framework for explaining much of the mutational data obtained for
      this complex.

PMID- 15557324
TI  - Transient versus sustained phosphorylation and nuclear accumulation of ERKs
      underlie anti-versus pro-apoptotic effects of estrogens.
AB  - Sex steroids exert anti-apoptotic effects on osteoblasts/osteocytes but exert pro
      apoptotic effects on osteoclasts, in both cases requiring activation of the
      extracellular signal-regulated kinases (ERKs). To explain the mechanistic basis
      of this divergence, we searched for differences in the kinetics of
      phosphorylation and/or in the subcellular localization of ERKs in response to
      17beta-estradiol in the two cell types. In contrast to its transient effect on
      ERK phosphorylation in osteocytic cells (return to base line by 30 min), 17beta
      estradiol-induced ERK phosphorylation in osteoclasts was sustained for at least
      24 h following exposure to the hormone. Conversion of sustained ERK
      phosphorylation to transient, by means of cholera toxin-induced activation of the
      adenylate cyclase/cAMP/protein kinase A pathway, abrogated the pro-apoptotic
      effect of 17beta-estradiol on osteoclasts. Conversely, prolongation of ERK
      activation in osteocytes, by means of leptomycin B-induced inhibition of ERK
      export from the nucleus or overexpression of a green fluorescent protein-ERK2
      mutant that resides permanently in the nucleus, converted the anti-apoptotic
      effect of 17beta-estradiol to a pro-apoptotic one. These findings indicate that
      the kinetics of ERK phosphorylation and the length of time that phospho-ERKs are
      retained in the nucleus are responsible for pro-versus anti-apoptotic effects of
      estrogen on different cell types of bone and perhaps their many other target
      tissues.

PMID- 15557325
TI  - The liver X receptor ligand T0901317 decreases amyloid beta production in vitro
      and in a mouse model of Alzheimer's disease.
AB  - Recent studies indicate that oxysterols, which are ligands for the nuclear
      hormone liver X receptors (LXR), decrease amyloid beta (Abeta) secretion in
      vitro. The effect was attributed primarily to the ATP-binding cassette
      transporter A1 (ABCA1) transcriptionally up-regulated by ligand-activated LXRs.
      We now examined the effect of the synthetic LXR ligand T0901317, which can be
      used in vivo, on Abeta production in vitro and in APP23 transgenic mice. T0901317
      applied to a variety of in vitro models, including immortalized fibroblasts from
      Tangier patients, and primary embryonic mouse neurons caused a concentration
      dependent decrease in Abeta secretion, and this effect was increased by the
      addition of apolipoprotein A-I. The inhibition of Abeta production by T0901317
      was cell-type specific, being more prominent in primary neurons than in non
      neuronal cells. Tangier fibroblasts lacking a functional ABCA1 secreted more
      Abeta than control fibroblasts, thus demonstrating the role of ABCA1 in amyloid
      precursor protein (APP) processing and Abeta generation. T0901317 treatment of 11
      week-old APP23 mice for 6 days showed a significant increase in ABCA1 expression
      and a decrease in the ratio of soluble APP (sAPP)beta- to sAPPalpha-cleavage
      products. Most importantly, the treatment caused a statistically significant
      reduction in the levels of soluble Abeta40 and of Abeta42 in the brain these
      mice. Our experiments demonstrate that T0901317 decreases amyloidogenic
      processing of APP in vitro and in vivo, thus supporting the search for potent and
      specific LXR ligands with properties allowing therapeutic application.

PMID- 15557326
TI  - Function-dependent conformational changes of the ABCG2 multidrug transporter
      modify its interaction with a monoclonal antibody on the cell surface.
AB  - The human ABCG2 protein is an important primary active transporter for
      hydrophobic compounds in several cell types, and its overexpression causes
      multidrug resistance in tumors. A monoclonal antibody (5D3) recognizes this
      protein on the cell surface. In ABCG2-expressing cells 5D3 antibody showed a
      saturable labeling and inhibited ABCG2 transport and ATPase function. However, at
      low antibody concentrations 5D3 binding to intact cells depended on the actual
      conformation of the ABCG2 protein. ATP depletion or the addition of the ABCG2
      inhibitor Ko143 significantly increased, whereas the vanadate-induced arrest of
      ABCG2 strongly decreased 5D3 binding. The binding of the 5D3 antibody to a non
      functional ABCG2 catalytic center mutant (K86M) in intact cells was not affected
      by the addition of vanadate but still increased with the addition of Ko143. In
      isolated membrane fragments the ligand modulation of 5D3 binding to ABCG2 could
      be analyzed in detail. In this case 5D3 binding was maximum in the presence of
      ATP, ADP, or Ko143, whereas the non-hydrolysable ATP analog, adenosine 5'
      (beta,gamma-imido)triphosphate (AMP-PNP), and nucleotide trapping by vanadate
      decreased antibody binding. In membranes expressing the ABCG2-K86M mutant, ATP,
      ADP, and AMP-PNP decreased, whereas Ko143 increased 5D3 binding. Based on these
      data we suggest that the 5D3 antibody can be used as a sensitive tool to reveal
      intramolecular changes, reflecting ATP binding, the formation of a catalytic
      intermediate, or substrate inhibition within the transport cycle of the ABCG2
      protein.

PMID- 15557327
TI  - Isolation and characterization of bifunctional Escherichia coli TatA mutant
      proteins that allow efficient tat-dependent protein translocation in the absence
      of TatB.
AB  - In Escherichia coli, the Tat system promotes the membrane translocation of a
      subset of exported proteins across the cytoplasmic membrane. Four genes (tatA,
      tatB, tatC, and tatE) have been identified that encode the components of the E.
      coli Tat translocation apparatus. Whereas TatA and TatE can functionally
      substitute for each other, the TatB and the TatC proteins have been shown to
      perform distinct functions. In contrast to Tat systems of the ABC(E) type found
      in E. coli and many other bacteria, some microorganisms possess a TatAC-type
      translocase that consists of TatA and TatC only, suggesting that, in these
      systems, TatB is not required or that one of the remaining components (TatA or
      TatC) additionally takes over the TatB function. We have addressed the molecular
      basis for the difference in subunit composition between TatABC(E) and TatAC-type
      systems by using a genetic approach. A plasmid-encoded E. coli minimal Tat
      translocase consisting solely of TatA and TatC was shown to mediate a low level
      translocation of a sensitive Tat-dependent reporter protein. Suppressor mutations
      in the minimal Tat translocase were isolated that compensate for the absence of
      TatB and that showed substantial increases in translocation activities. All of
      the mutations mapped to the extreme amino-terminal domain of TatA. No mutations
      affecting TatC were identified. These results suggest that in TatAC-type systems,
      the TatA protein represents a bifunctional component fulfilling both the TatA and
      TatB functions. Furthermore, our results indicate that the structure of the amino
      terminal domain of TatA is decisive for whether or not TatB is required.

PMID- 15557328
TI  - Down-regulation of iron regulatory protein 1 activities and expression in
      superoxide dismutase 1 knock-out mice is not associated with alterations in iron
      metabolism.
AB  - Iron and oxygen (O2) are intimately associated in many well characterized patho
      physiological processes. These include oxidation of the [4Fe-4S] cluster of
      mitochondrial aconitase and inactivation of this Krebs cycle enzyme by the
      superoxide anion (O2*-), a product of the one-electron of reduction O2. In
      contrast to the apparent toxicity of this reaction, the biological consequences
      of O2*- -mediated inactivation of the cytosolic counterpart of mitochondrial
      aconitase, commonly known as iron regulatory protein 1 (IRP1), are not clear.
      Apart from its ability to convert citrate to iso-citrate, IRP1 in its apo-form
      binds to iron-responsive elements in the untranslated regions of mRNAs coding for
      proteins involved in iron metabolism, to regulate their synthesis and thus
      control the cellular homeostasis of this metal. Here, we show that in superoxide
      dismutase 1 (SOD1) knock-out mice, lacking Cu,Zn-SOD, an enzyme that acts to
      reduce the concentration of O2*- mainly in cytosol, not only is aconitase
      activity of IRP1 inhibited but the level of IRP1 is also strongly decreased.
      Despite such an evident alteration in IRP1 status, SOD1-deficient mice display a
      normal iron metabolism phenotype. Our findings clearly show that under conditions
      of O2*- -mediated oxidative stress, IRP1 is not essential for the maintenance of
      iron metabolism in mammals.

PMID- 15557329
TI  - Peptide mapping identifies hotspot site of modification in human serum albumin by
      methylglyoxal involved in ligand binding and esterase activity.
AB  - Methylglyoxal is a potent glycating agent under physiological conditions. Human
      serum albumin is modified by methylglyoxal in vivo. The glycation adducts formed
      and structural and functional changes induced by methylglyoxal modification have
      not been fully disclosed. Methylglyoxal reacted with human serum albumin under
      physiological conditions to form mainly the hydroimidazolone N(delta)-(5-hydro-5
      methyl-4-imidazolon-2-yl)-ornithine (92% of total modification) with a minor
      formation of argpyrimidine, N(epsilon)-(1-carboxyethyl)lysine, and methylglyoxal
      lysine dimer. When human serum albumin was modified minimally with methylglyoxal,
      tryptic peptide mapping indicated a hotspot of modification at Arg-410 located in
      drug-binding site II and the active site of albumin-associated esterase activity.
      Modification of Arg-410 by methylglyoxal was found in albumin glycated in vivo.
      Other sites of minor modification were: Arg-114, Arg-186, Arg-218, and Arg-428.
      Hydroimidazolone formation at Arg-410 inhibited ketoprofen binding and esterase
      activity; correspondingly, glycation in the presence of ketoprofen inhibited Arg
      410 modification and loss of esterase activity. The pH dependence of esterase
      activity indicated a catalytic group with pK(a) = 7.9 +/- 0.1, assigned to the
      catalytic base Tyr-411 with the conjugate base stabilized by interaction with the
      guanidinium group of Arg-410. Modification by methylglyoxal destabilized Tyr-411
      and increased the pK(a) to 8.8 +/- 0.1. Molecular dynamics and modeling studies
      indicated that hydroimidazolone formation caused structural distortion leading to
      disruption of arginine-directed hydrogen bonding and loss of electrostatic
      interactions. Methylglyoxal modification of critical arginine residues,
      therefore, whether experimental or physiological, is expected to disrupt protein
      ligand interactions and inactivate enzyme activity by hydroimidazolone formation.

PMID- 15557330
TI  - Structure of the C-terminal domain from Trypanosoma brucei variant surface
      glycoprotein MITat1.2.
AB  - The variant surface glycoprotein (VSG) of African trypanosomes has a structural
      role in protecting other cell surface proteins from effector molecules of the
      mammalian immune system and also undergoes antigenic variation necessary for a
      persistent infection in a host. Here we have reported the solution structure of a
      VSG type 2 C-terminal domain from MITat1.2, completing the first structure of
      both domains of a VSG. The isolated C-terminal domain is a monomer in solution
      and forms a novel fold, which commences with a short alpha-helix followed by a
      single turn of 3(10)-helix and connected by a short loop to a small anti-parallel
      beta-sheet and then a longer alpha-helix at the C terminus. This compact domain
      is flanked by two unstructured regions. The structured part of the domain
      contains 42 residues, and the core comprises 2 disulfide bonds and 2 hydrophobic
      residues. These cysteines and hydrophobic residues are conserved in other VSGs,
      and we have modeled the structures of two further VSG C-terminal domains using
      the structure of MITat1.2. The models suggest that the overall structure of the
      core is conserved in the different VSGs but that the C-terminal alpha-helix is of
      variable length and depends on the presence of charged residues. The results
      provided evidence for a conserved tertiary structure for all the type 2 VSG C
      terminal domains, indicated that VSG dimers form through interactions between N
      terminal domains, and showed that the selection pressure for sequence variation
      within a conserved tertiary structure acts on the whole of the VSG molecule.

PMID- 15557331
TI  - Mutational analysis of essential interactions involved in the assembly of
      hepatitis E virus capsid.
AB  - The hepatitis E virus (HEV) capsid consists of a single structural protein, a
      portion of which is engaged in isosahedral contact to form a basal shell, and
      another portion in dimeric contact to form the homodimers protruding from the
      shell. Previous studies revealed that homodimers of the truncated HEV capsid
      proteins, E2 (amino acids 394-606) and p239 (amino acids 368-606), model dominant
      antigenic determinants of HEV. Immunization with these proteins protected rhesus
      monkeys against the virus, and three monoclonal antibodies against the homodimers
      could neutralize HEV infectivity and/or immune-capture of the virus. Furthermore,
      homodimers of p239 further interact to form particles of 23 nm diameter,
      rendering it an efficacious candidate vaccine. In light of this we postulate that
      the interactions involved in the formation of the homodimers and particles might
      be similar to those involved in assembly of the virus capsid. Presently,
      mutational analysis was carried out to identify these sites of interactions. The
      site of dimeric interactions was located to a cluster of six hydrophobic amino
      acids residues, Ala597, Val598, Ala599, Leu601, and Ala602; furthermore, the site
      involved in particle formation was located at amino acids 368-394. The
      possibility that these sites are also involved in assembly of the virus capsid is
      supported by the fact that they are located at two major and highly conserved
      hydrophobic regions of the HEV structural protein.

PMID- 15557332
TI  - Insulin and contraction stimulate exocytosis, but increased AMP-activated protein
      kinase activity resulting from oxidative metabolism stress slows endocytosis of
      GLUT4 in cardiomyocytes.
AB  - Stimulations of glucose transport produced by insulin action, contraction, or
      through a change in cell energy status are mediated by separate signaling
      pathways. These are the wortmannin-sensitive phosphatidylinositol 3-kinase
      pathway leading to the intermediate Akt and the wortmannin-insensitive AMP
      activated protein kinase (AMPK) pathway. Electrical stimulation of cardiomyocytes
      produced a rapid, insulin-like, wortmannin-sensitive stimulation of glucose
      transport activity, but this occurred without extensive activation of Akt.
      Although AMPK phosphorylation was increased by contraction, this response was not
      wortmannin-inhibitable and consequently did not correlate with the wortmannin
      sensitivity of the transport stimulation. Oxidative metabolism stress due to
      hypoxia or treatment with oligomycin led to increased AMPK activity with a
      corresponding increase in glucose transport activity. We show here that these
      separate signaling pathways converge on GLUT4 trafficking at separate steps. The
      rate of exocytosis of GLUT4 was rapidly stimulated by insulin, but insulin
      treatment did not alter the endocytosis rate. Like insulin stimulation,
      electrical stimulation of contraction led to a stimulation of GLUT4 exocytosis
      without any marked change in endocytosis. By contrast, after oxidative metabolism
      stress, no stimulation of GLUT4 exocytosis occurred; instead, this treatment led
      to a reduction in GLUT4 endocytosis.

PMID- 15557333
TI  - Analysis of mitotic and expression properties of human neocentromere-based
      transchromosomes in mice.
AB  - Human neocentromeres are functional centromeres that are devoid of the typical
      human centromeric alpha-satellite DNA. We have transferred a 60-Mb chromosome 10
      derived neocentric marker chromosome, mardel(10), and its truncated 3.5-Mb
      derivative, NC-MiC1, into mouse embryonic stem cell and have demonstrated a
      relatively high structural and mitotic stability of the transchromosomes in a
      heterologous genetic background. We have also produced chimeric mice carrying
      mardel(10) or NC-MiC1. Both transchromosomes were detected as intact episomal
      entities in a variety of adult chimeric mouse tissues including hemopoietic stem
      cells. Genes residing on these transchromosomes were expressed in the different
      tissues tested. Meiotic transmission of both transchromosomes in the chimeric
      mice was evident from the detection of DNA from these chromosomes in sperm
      samples. In particular, germ line transmission of NC-MiC1 was demonstrated in the
      F1 embryos of the chimeric mice. Variable (low in mardel(10)- or NC-MiC1
      containing embryonic stem cells and chimeric mouse tissues and relatively high in
      NC-MiC1-containing F1 embryos) levels of missegregation of these transchromosomes
      were detected, suggesting that they are not optimally predisposed to full mitotic
      regulation in the mouse background, particularly during early embryogenesis.
      These results provide promising data in support of the potential use of
      neocentromere-based human marker chromosomes and minichromosomes as a tool for
      the study of centromere, neocentromere, and chromosome biology and for gene
      therapy studies in a mouse model system. They also highlight the need to further
      understand and overcome the factors that are responsible for the definable rates
      of instability of these transchromosomes in a mouse model.

PMID- 15557334
TI  - Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells.
AB  - Oct-3/4 is a key transcriptional factor whose expression level governs the fate
      of primitive inner cell mass and embryonic stem (ES) cells. Previously, an
      upstream 3.3-kb distal enhancer (DE) fragment was identified to be responsible
      for the specific expression of mouse Oct-3/4 in the inner cell mass and ES cells.
      However, little is known about the cis-elements and trans-factors required for DE
      activity. In this study, we identified a novel cis-element, called Site 2B here,
      located approximately 30 bp downstream from Site 2A, which was previously
      revealed in DE by an in vivo chemical modification experiment. Using the
      luciferase reporter assay, we demonstrated that both Site 2A and Site 2B are
      necessary and sufficient for activating DE in the contexts of both the native Oct
      3/4 promoter and the heterologous thymidine kinase minimal promoter. In an
      electrophoretic mobility shift assay we showed that Site 2B specifically binds to
      Oct-3/4 and Sox2 when ES-derived cell extracts were used, whereas Site 2A binds
      to a factor(s) present in both ES and NIH 3T3 cells. Furthermore, we showed that
      the physiological level of Oct-3/4 in ES cells is required for Site 2B-mediated
      DE activity using the inducible knock-out system of Oct-3/4 in ES cells. These
      results indicate that Oct-3/4 is a member of the gene family regulated by Oct-3/4
      and Sox2, as reported before for the FGF-4, UTF1, Sox2, and Fbx15 genes. Thus,
      Oct-3/4 and Sox2 comprise a regulatory complex that controls the expression of
      genes important for the maintenance of the primitive state, including themselves.
      This autoregulatory circuit of the Sox2.Oct-3/4 complex may contribute to
      maintaining robustly the precise expression level of Oct-3/4 in primitive cells.

PMID- 15557335
TI  - Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners
      and antagonizes its activities.
AB  - Alix/AIP1 is an adaptor protein involved in regulating the function of receptor
      and cytoskeleton-associated tyrosine kinases. Here, we investigated its
      interaction with and regulation by Src. Tyr319 of Alix bound the isolated Src
      homology-2 (SH2) domain and was necessary for interaction with intact Src. A
      proline-rich region in the C terminus of Alix bound the Src SH3 domain, but this
      interaction was dependent on the release of the Src SH2 domain from its Src
      internal ligand either by interaction with Alix Tyr319 or by mutation of Src
      Tyr527. Src phosphorylated Alix at a C-terminal region rich in tyrosines, an
      activity that was stimulated by the presence of the Alix binding partner
      SETA/CIN85. Phosphorylation of Alix by Src caused it to translocate from the
      membrane and cytoskeleton to the cytoplasm and reduced its interaction with
      binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2. As a
      consequence of this, Src antagonized the negative regulation of receptor tyrosine
      kinase internalization and cell adhesion by Alix. We propose a model whereby Src
      antagonizes the effects of Alix by phosphorylation of its C terminus, leading to
      the disruption of interactions with target proteins.

PMID- 15557336
TI  - Photobiomodulation directly benefits primary neurons functionally inactivated by
      toxins: role of cytochrome c oxidase.
AB  - Far red and near infrared (NIR) light promotes wound healing, but the mechanism
      is poorly understood. Our previous studies using 670 nm light-emitting diode
      (LED) arrays suggest that cytochrome c oxidase, a photoacceptor in the NIR range,
      plays an important role in therapeutic photobiomodulation. If this is true, then
      an irreversible inhibitor of cytochrome c oxidase, potassium cyanide (KCN),
      should compete with LED and reduce its beneficial effects. This hypothesis was
      tested on primary cultured neurons. LED treatment partially restored enzyme
      activity blocked by 10-100 microm KCN. It significantly reduced neuronal cell
      death induced by 300 microm KCN from 83.6 to 43.5%. However, at 1-100 mm KCN, the
      protective effects of LED decreased, and neuronal deaths increased. LED
      significantly restored neuronal ATP content only at 10 microm KCN but not at
      higher concentrations of KCN tested. Pretreatment with LED enhanced efficacy of
      LED during exposure to 10 or 100 microm KCN but did not restore enzyme activity
      to control levels. In contrast, LED was able to completely reverse the
      detrimental effect of tetrodotoxin, which only indirectly down-regulated enzyme
      levels. Among the wavelengths tested (670, 728, 770, 830, and 880 nm), the most
      effective ones (830 nm, 670 nm) paralleled the NIR absorption spectrum of
      oxidized cytochrome c oxidase, whereas the least effective wavelength, 728 nm,
      did not. The results are consistent with our hypothesis that the mechanism of
      photobiomodulation involves the up-regulation of cytochrome c oxidase, leading to
      increased energy metabolism in neurons functionally inactivated by toxins.

PMID- 15557337
TI  - Prosurvival and prodeath effects of hypoxia-inducible factor-1alpha stabilization
      in a murine hippocampal cell line.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in
      adaptation to hypoxic stress. Previous studies from our laboratory demonstrated
      that pharmacological activators of HIF-1 (e.g. deferoxamine, cobalt chloride)
      could also protect cultured primary neurons or an immortalized hippocampal
      neuroblast line (HT22) from oxidative stress-induced death. However, whether HIF
      1 activation is sufficient to abrogate neuronal death resulting from oxidative
      stress or other hypoxia-independent death inducers remains unclear. To address
      this question we utilized a HIF-1alpha fusion protein that partially lacks the
      domain required for oxygen-dependent degradation of HIF-1alpha and that has a
      VP16 transcriptional activation domain from herpes simplex virus. HT22 cells were
      infected with a retrovirus encoding either the HIF-1alpha-VP16 fusion protein or
      the activation domain of the VP16 protein alone as a control. Expression of HIF
      1alpha-VP16, but not VP16 alone, increased luciferase activity driven by a
      canonical hypoxia response element, increased mRNA of established HIF-1 target
      genes, and increased activity of one of these HIF-1 target genes. Unexpectedly,
      enhanced HIF-1 activity in HT22 cells enhanced sensitivity to oxidative death
      induced by glutathione depletion. Accordingly, suppression of HIF-1alpha
      expression using RNA interference prevented oxidative death. By contrast, HIF
      1alpha-VP16-expressing HT22 cells were more resistant to DNA damage (induced by
      camptothecin) or endoplasmic reticulum stress (induced by thapsigargin and
      tunicamycin) than were VP16-expressing cells, and suppression of HIF-1alpha
      expression using RNA interference rendered HT22 cells more sensitive to death
      induced by DNA damage or endoplasmic reticulum stress. Together, these data
      demonstrate that HIF-1 can mediate prodeath or prosurvival responses in the same
      cell type depending on the injury stimulus.

PMID- 15557338
TI  - Involvement of the phosphatidylinositol 3-kinase/rac1 and cdc42 pathways in
      radial migration of cortical neurons.
AB  - During cortical development, newly generated neurons migrate radially toward
      their final positions. Although several candidate genes essential for this radial
      migration have been reported, the signaling pathways regulating it are largely
      unclear. Here we studied the role of phosphatidylinositol (PI) 3-kinase and its
      downstream signaling molecules in the radial migration of cortical neurons in
      vivo and in vitro. The expression of constitutively active and dominant-negative
      PI 3-kinases markedly inhibited radial migration. In the neocortical slice
      culture, a PI 3-kinase inhibitor suppressed the formation of GTP-bound Rac1 and
      Cdc42 and radial migration. Constitutively active and dominant-negative forms of
      Rac1 and Cdc42 but not Akt also significantly inhibited radial migration. In
      migrating neurons, wild-type Rac1 and Cdc42 showed different localizations; Rac1
      localized to the plasma membrane and Cdc42 to the perinuclear region on the side
      of the leading processes. These results suggest that both the PI 3-kinase/Rac1
      and Cdc42 pathways are involved in the radial migration of cortical neurons and
      that they have different roles.

PMID- 15557339
TI  - Competition of electrons to enter the respiratory chain: a new regulatory
      mechanism of oxidative metabolism in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the most important systems for conveying
      excess cytosolic NADH to the mitochondrial respiratory chain are the external
      NADH dehydrogenases (Nde1p and Nde2p) and the glycerol-3-phosphate dehydrogenase
      shuttle. In the latter system, NADH is oxidized to NAD+ and dihydroxyacetone
      phosphate is reduced to glycerol 3-phosphate by the cytosolic Gpd1p.
      Subsequently, glycerol 3-phosphate donates electrons to the respiratory chain via
      mitochondrial glycerol-3-phosphate dehydrogenase (Gut2p). At saturating
      concentrations of NADH, the activation of external NADH dehydrogenases completely
      inhibits glycerol 3-phosphate oxidation. Studies on the functionally isolated
      enzymes demonstrated that neither Nde1p nor Nde2p directly inhibits Gut2p. Thus,
      the inhibition of glycerol 3-phosphate oxidation may be caused by competition for
      the entrance of electrons into the respiratory chain. Using single deletion
      mutants of Nde1p or Nde2p, we have shown that glycerol 3-phosphate oxidation via
      Gut2p is inhibited fully when NADH is oxidized via Nde1p, whereas only 50% of
      glycerol 3-phosphate oxidation is inhibited when Nde2p is functioning. By
      comparing respiratory rates with different respiratory substrates, we show that
      electrons from Nde1p are favored over electrons coming from Ndip (internal NADH
      dehydrogenase) and that when electrons come from either Nde1p or Nde2p and
      succinodehydrogenase, their use by the respiratory chain is shared to a
      comparable extent. This suggests a very specific competition for electron
      entrance into the respiratory chain, which may be caused by the supramolecular
      organization of the respiratory chain. The physiological consequences of such
      regulation are discussed.

PMID- 15557340
TI  - Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity.
AB  - Mutations in the PARKIN gene are the most common cause of hereditary
      parkinsonism. The parkin protein comprises an N-terminal ubiquitin-like domain, a
      linker region containing caspase cleavage sites, a unique domain in the central
      portion, and a special zinc finger configuration termed RING-IBR-RING. Parkin has
      E3 ubiquitin-protein ligase activity and is believed to mediate proteasomal
      degradation of aggregation-prone proteins. Whereas the effects of mutations on
      the structure and function of parkin have been intensely studied, post
      translational modifications of parkin and the regulation of its enzymatic
      activity are poorly understood. Here we report that parkin is phosphorylated both
      in human embryonic kidney HEK293 cells and human neuroblastoma SH-SY5Y cells. The
      turnover of parkin phosphorylation was rapid, because inhibition of phosphatases
      with okadaic acid was necessary to stabilize phosphoparkin. Phosphoamino acid
      analysis revealed that phosphorylation occurred mainly on serine residues under
      these conditions. At least five phosphorylation sites were identified, including
      Ser101, Ser131, and Ser136 (located in the linker region) as well as Ser296 and
      Ser378 (located in the RING-IBR-RING motif). Casein kinase-1, protein kinase A,
      and protein kinase C phosphorylated parkin in vitro, and inhibition of casein
      kinase-1 caused a dramatic reduction of parkin phosphorylation in cell lysates.
      Induction of protein folding stress in cells reduced parkin phosphorylation, and
      unphosphorylated parkin had slightly but significantly elevated
      autoubiquitination activity. Thus, complex regulation of the phosphorylation
      state of parkin may contribute to the unfolded protein response in stressed
      cells.

PMID- 15557341
TI  - Analysis of SHP-1-mediated down-regulation of the TRK-T3 oncoprotein identifies
      Trk-fused gene (TFG) as a novel SHP-1-interacting protein.
AB  - SHP-1 is a cytoplasmic SH2 domain containing protein-tyrosine phosphatase (PTP)
      involved in the negative regulation of multiple signaling pathways in
      hematopoietic, nervous, and epithelial cells. The thyroid TRK-T3 oncogene
      consists of the NTRK1 tyrosine kinase domain fused in-frame with sequences of the
      TFG (TRK-fused gene), encoding a protein of unknown function. TFG contains a
      coiled-coil domain responsible for TRK-T3 oligomerization. In addition, recent
      analysis of the sequences outside of the coiled-coil domain suggested possible
      interactions with other proteins. Based on the presence of a putative SHP-1 SH2
      binding site within the TFG sequences, we have investigated the role of the SHP-1
      phosphatase in TRK-T3 oncoprotein signaling. In this study we show that SHP-1
      interacts with and down-regulates TRK-T3. We provide evidence that SHP-1 SH2 and
      catalytic domains, respectively, associate with the TFG- and NTRK1-derived
      portions of TRK-T3. Our data contribute to the definition of cellular mechanisms
      involved in thyroid tumorigenesis. Moreover, it reveals TFG as a novel protein
      able to modulate SHP-1 activity.

PMID- 15557342
TI  - Real-time monitoring of the PDE2 activity of live cells: hormone-stimulated cAMP
      hydrolysis is faster than hormone-stimulated cAMP synthesis.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are the enzymes that catalyze the
      hydrolysis of cAMP and cGMP, thereby restricting the activity of these second
      messengers in cells. A unique ability to shape gradients of cyclic nucleotides
      and compartmentalize their signaling implies a high potency and a rapid action of
      PDEs. However, it has not been demonstrated how fast PDEs can hydrolyze cAMP in a
      living system. Here we perform a real-time monitoring of PDE2 activity in
      aldosterone-producing adrenal cells using a recently developed genetically
      encoded, fluorescent cAMP sensor, which reveals enormously rapid kinetics of cAMP
      degradation. Activation of PDE2 results in a rapid decrease of intracellular cAMP
      from high micromolar to the sub-micromolar range within a few seconds. Moreover,
      the kinetics of atrial natriuretic peptide-stimulated PDE2 activity (measured as
      decline of cAMP) are much faster than the speed of ACTH and isoprenaline-induced
      cAMP-synthesis (measured as cAMP accumulation) in the cells, revealing high
      catalytic activity and fast action of PDEs in regulating cAMP signaling in a
      physiological system.

PMID- 15557343
TI  - Calcineurin inhibits Na+/Ca2+ exchange in phenylephrine-treated hypertrophic
      cardiomyocytes.
AB  - The cardiac Na(+)/Ca(2+) exchanger (NCX1) is the predominant mechanism for the
      extrusion of Ca(2+) from beating cardiomyocytes. The role of protein
      phosphorylation in the regulation of NCX1 function in normal and diseased hearts
      remains unclear. In our search for proteins that interact with NCX1 using a yeast
      two-hybrid screen, we found that the C terminus of calcineurin Abeta, containing
      the autoinhibitory domain, binds to the beta1 repeat of the central cytoplasmic
      loop of NCX1 that presumably constitutes part of the allosteric Ca(2+) regulatory
      site. The association of NCX1 with calcineurin was significantly increased in the
      BIO14.6 cardiomyopathic hamster heart compared with that in the normal control.
      In hypertrophic neonatal rat cardiomyocytes subjected to chronic phenylephrine
      treatment, we observed a marked depression of NCX activity measured as the rate
      of Na(+)(i)-dependent (45)Ca(2+) uptake or the rate of Na(+)(o)-dependent
      (45)Ca(2+) efflux. Depressed NCX activity was partially and independently
      reversed by the acute inhibition of calcineurin and protein kinase C activities
      with little effect on myocyte hypertrophic phenotypes. Studies of NCX1 deletion
      mutants expressed in CCL39 cells were consistent with the view that the beta1
      repeat is required for the action of endogenous calcineurin and that the large
      cytoplasmic loop may be required to maintain the interaction of the enzyme with
      its substrate. Our data suggest that NCX1 is a novel regulatory target for
      calcineurin and that depressed NCX activity might contribute to the etiology of
      in vivo cardiac hypertrophy and dysfunction occurring under conditions in which
      both calcineurin and protein kinase C are chronically activated.

PMID- 15557344
TI  - Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes.
AB  - The synthetic opioid alfentanil is an analgesic and an in vivo probe for hepatic
      and first-pass CYP3A activity. Alfentanil is a particularly useful CYP3A probe
      because pupil diameter change is a surrogate for plasma concentrations, thereby
      affording noninvasive assessment of CYP3A. Alfentanil undergoes extensive CYP3A4
      metabolism via two major pathways, forming noralfentanil and N
      phenylpropionamide. This investigation evaluated alfentanil metabolism in vitro
      to noralfentanil and N-phenylpropionamide, by expressed CYP3A5 and CYP3A7 in
      addition to CYP3A4, with and without coexpressed or exogenous cytochrome b(5).
      Effects of the CYP3A inhibitors troleandomycin and ketoconazole were also
      determined. Rates of noralfentanil and N-phenylpropionamide formation by CYP3A4
      and 3A5 in the absence of b(5) were generally equivalent, although the metabolite
      formation ratio differed, whereas those by CYP3A7 were substantially less. CYP3A4
      and 3A5 were equipotently inhibited by troleandomycin, whereas ketoconazole was
      an order of magnitude more potent toward CYP3A4. Cytochrome b(5) qualitatively
      and quantitatively altered alfentanil metabolism, with b(5) coexpression having a
      greater effect than exogenous addition. Addition or coexpression of b(5) markedly
      stimulated the formation of both metabolites and changed the formation of
      noralfentanil but not N-phenylpropionamide from apparent single-site to multisite
      Michaelis-Menten kinetics. These results demonstrate that alfentanil is a
      substrate for CYP3A5 in addition to CYP3A4, and the effects of the CYP3A
      inhibitors troleandomycin and ketoconazole are CYP3A enzyme-selective. Alfentanil
      is one of the few CYP3A substrates that is metabolized in vitro as avidly by both
      CYP3A4 and 3A5. Polymorphic CYP3A5 expression may contribute to inter-individual
      variability in alfentanil metabolism.

PMID- 15557345
TI  - Malathion bioactivation in the human liver: the contribution of different
      cytochrome p450 isoforms.
AB  - Among organophosphorothioate (OPT) pesticides, malathion is considered relatively
      safe for use in mammals. Its rapid degradation by carboxylesterases competes with
      the cytochrome P450 (P450)-catalyzed formation of malaoxon, the toxic metabolite.
      However, impurities in commercial formulations are potent inhibitors of
      carboxylesterase, allowing a dramatic increase in malaoxon formation. Malathion
      desulfuration has been characterized in human liver microsomes (HLMs) with a
      method based on acetylcholinesterase inhibition that is able to detect nanomolar
      levels of oxon. The active P450 isoforms have been identified by means of a
      multifaceted strategy, including the use of cDNA-expressed human P450s and
      correlation, immunoinhibition, and chemical inhibition studies in a panel of
      phenotyped HLMs. HLMs catalyzed malaoxon formation with a high level of
      variability (>200-fold). One or two components (K(mapp1) = 53-67 microM; K(mapp2)
      = 427-1721 microM) were evidenced, depending on the relative specific P450
      content. Results from different approaches indicated that, at low malathion
      concentration, malaoxon formation is catalyzed by CYP1A2 and, to a lesser extent,
      2B6, whereas the role of 3A4 is relevant only at high malathion levels. These
      results are in line with those found with chlorpyrifos, diazinon, azynphos
      methyl, and parathion, characterized by the presence of an aromatic ring in the
      molecule. Since malathion has linear chains as substituents at the thioether
      sulfur, it can be hypothesized that, independently from the chemical structure,
      OPTs are bioactivated by the same P450s. These results also suggest that CYP1A2
      and 2B6 can be considered as possible metabolic biomarkers of susceptibility to
      OPT-induced toxic effects at actual human exposure levels.

PMID- 15557346
TI  - Structural basis for the restoration of TCR recognition of an MHC allelic variant
      by peptide secondary anchor substitution.
AB  - Major histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8)
      differ primarily in the B pocket of the peptide-binding groove, which serves to
      sequester the P2 secondary anchor residue. This polymorphism determines
      resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell
      responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We studied
      the molecular basis of these effects and confirmed that T cell receptors raised
      against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution of
      Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition; H
      2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the
      structural basis of this discrimination was obtained by determining the crystal
      structures of all four MHC class I molecules in complex with bound peptide
      (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can
      explain the differential TCR recognition. However, a correlation is apparent
      between the recognition data and the underlying peptide-binding groove chemistry
      of the B pocket, revealing that secondary anchor residues can profoundly affect
      TCR engagement through mechanisms distinct from the alteration of the resting
      state conformation of the pMHC surface.

PMID- 15557347
TI  - A soluble form of the triggering receptor expressed on myeloid cells-1 modulates
      the inflammatory response in murine sepsis.
AB  - The triggering receptor expressed on myeloid cells (TREM)-1 is a recently
      discovered receptor expressed on the surface of neutrophils and a subset of
      monocytes. Engagement of TREM-1 has been reported to trigger the synthesis of
      proinflammatory cytokines in the presence of microbial products. Previously, we
      have identified a soluble form of TREM-1 (sTREM-1) and observed significant
      levels in serum samples from septic shock patients but not controls. Here, we
      investigated its putative role in the modulation of inflammation during sepsis.
      We observed that sTREM-1 was secreted by monocytes activated in vitro by LPS and
      in the serum of animals involved in an experimental model of septic shock. Both
      in vitro and in vivo, a synthetic peptide mimicking a short highly conserved
      domain of sTREM-1 appeared to attenuate cytokine production by human monocytes
      and protect septic animals from hyper-responsiveness and death. This peptide
      seemed to be efficient not only in preventing but also in down-modulating the
      deleterious effects of proinflammatory cytokines. These data suggest that in vivo
      modulation of TREM-1 by sTREM peptide might be a suitable therapeutic tool for
      the treatment of sepsis.

PMID- 15557348
TI  - Clonal type I interferon-producing and dendritic cell precursors are contained in
      both human lymphoid and myeloid progenitor populations.
AB  - Because of different cytokine responsiveness, surface receptor, and transcription
      factor expression, human CD11c(-) natural type I interferon-producing cells
      (IPCs) and CD11c(+) dendritic cells were thought to derive through lymphoid and
      myeloid hematopoietic developmental pathways, respectively. To directly test this
      hypothesis, we used an in vitro assay allowing simultaneous IPC, dendritic cell,
      and B cell development and we tested lymphoid and myeloid committed hematopoietic
      progenitor cells for their developmental capacity. Lymphoid and common myeloid
      and granulocyte/macrophage progenitors were capable of developing into both
      functional IPCs, expressing gene transcripts thought to be associated with
      lymphoid lineage development, and into dendritic cells. However, clonal
      progenitors for both populations were about fivefold more frequent within myeloid
      committed progenitor cells. Thus, in humans as in mice, natural IPC and dendritic
      cell development robustly segregates with myeloid differentiation. This would fit
      with natural interferon type I-producing cell and dendritic cell activity in
      innate immunity, the evolutionary older arm of the cellular immune system.

PMID- 15557349
TI  - Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing
      lymphocytes to the liver in primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease
      characterized by progressive bile duct destruction, develops as an extra
      intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991.
      Gut. 32:1433-1435). However, the liver and bowel inflammation are rarely
      concomitant, and PSC can develop in patients whose colons have been removed
      previously. We hypothesized that PSC is mediated by long-lived memory T cells
      originally activated in the gut, but able to mediate extra-intestinal
      inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S.
      Jalkanen, and D.H. Adams. 2002. Lancet. 359:150-157). In support of this, we show
      that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to
      the liver by aberrant expression of the gut-specific chemokine CCL25 that
      activates alpha4beta7 binding to mucosal addressin cell adhesion molecule 1 on
      the hepatic endothelium. This is the first demonstration in humans that T cells
      activated in the gut can be recruited to an extra-intestinal site of disease and
      provides a paradigm to explain the pathogenesis of extra-intestinal complications
      of IBD.

PMID- 15557350
TI  - Functional reprogramming of the primary immune response by T cell receptor
      antagonism.
AB  - The T cell receptor must translate modest, quantitative differences in ligand
      binding kinetics into the qualitatively distinct signals used to determine cell
      fate. Here, we use mice that express an endogenous T cell receptor (TCR)
      antagonist and an adoptive transfer system to examine the influence of TCR signal
      quality on the development of effector function. We show that activation of
      antigen-specific T cells in the presence of an antagonist results in a functional
      reprogramming of the primary immune response, marked by altered T cell homing, a
      failure to develop effector function, and ultimately clonal elimination by
      apoptosis. Importantly, antagonism does not block cell division, implying that
      the signals promoting clonal expansion and effector differentiation are distinct.

PMID- 15557351
TI  - Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after
      Mycobacterium tuberculosis infection.
AB  - Optimum immunity against Mycobacterium tuberculosis requires both CD4(+) and
      CD8(+) T cells. In contrast with CD4(+) T cells, few antigens are known that
      elicit CD8(+) T cells during infection. CD8(+) T cells specific for culture
      filtrate protein-10 (CFP10) are found in purified protein derivative positive
      donors, suggesting that CFP10 primes CD8(+) T cells in vivo. Using T cells from
      M. tuberculosis-infected mice, we identified CFP10 epitopes recognized by CD8(+)
      T cells and CD4(+) T cells. CFP10-specific T cells were detected as early as week
      3 after infection and at their peak accounted for up to 30% of CD8(+) T cells in
      the lung. IFNgamma-producing CD8(+) and CD4(+) T cells recognizing CFP10 epitopes
      were preferentially recruited to the lungs of M. tuberculosis-infected mice. In
      vivo cytolytic activity of CD8(+) T cells specific for CFP10 and TB10.3/10.4
      proteins was detected in the spleen, pulmonary lymph nodes, and lungs of infected
      mice. The cytolytic activity persisted long term and could be detected 260 d
      after infection. This paper highlights the cytolytic function of antigen-specific
      CD8(+) T cells elicited by M. tuberculosis infection and demonstrates that large
      numbers of CFP10-specific cytolytic CD8(+) T cells are recruited to the lung
      after M. tuberculosis infection.

PMID- 15557352
TI  - Adjustment for patient characteristics in satisfaction surveys.

PMID- 15557353
TI  - Patient perceptions of service quality in group versus solo practice clinics.
AB  - OBJECTIVE: To compare patient perceptions of service quality at solo and group
      practices, and to examine the association of perceptions with 'potential patient
      loyalty' (PPL), the potential for seeking future service from the same clinic.
      DESIGN: A self-administered, cross-sectional survey of clinic outpatients, using
      an adapted SERVQUAL questionnaire translated into Chinese, with additional items
      on overall satisfaction and intent to return/recommend the clinic to others.
      Sampling and study subjects. Every third outpatient at all newly started group
      practices (four) and solo clinics (thirteen) in Taiwan in the preceding 4-7
      months, including 150 and 50 patients from each group and solo practice,
      respectively, for a total of 1250 patients. MAIN OUTCOME MEASURES: Perceived
      service quality on five dimensions-tangibles, reliability, responsiveness,
      assurance, and empathy-and PPL. All constructs were measured on a five-point
      scale. RESULTS: After accounting for random effects of clinical and geographical
      location, group practice patients perceived significantly higher service quality
      on all dimensions relative to solo practice patients, after adjusting for age,
      gender, education, and illness type. All service quality dimensions except
      assurance were significantly positively associated with PPL after adjusting for
      age, gender, education, and illness type, and random effects at the clinical and
      geographical location levels. CONCLUSIONS: Patients perceive better service
      quality at group practices compared with solo practices on all dimensions.
      Patients' quality perceptions are significant predictors of PPL. The implications
      for physician practices both internationally and in Taiwan are discussed, as well
      as policy implications for the Taiwan government.

PMID- 15557354
TI  - Measuring client-perceived quality of maternity services in rural Vietnam.
AB  - OBJECTIVE: To examine the feasibility, reliability and validity of a 20-item
      scale for measuring perceived quality of maternity services provided at commune
      health centres in rural Vietnam. DESIGN: A survey of 200 women who gave birth in
      July-August 2000 and 196 pregnant women in 34 communes in Quang Xuong District,
      Thanh Hoa Province, Vietnam. MAIN OUTCOME MEASURES: Inter-rater reliability,
      internal consistency and factor structure of the scale were examined. The
      associations between perceived quality and client characteristics were also
      investigated. RESULTS: The instrument had relatively good inter-rater reliability
      and internal consistency. Except for two items: 'good clinical examination' and
      'adequacy of health workers for women's health', the scale exhibited good
      agreement between the two raters, with kappa values ranging from 0.54 to 0.84.
      The Cronbach's alpha coefficients for the dimensions 'health care delivery',
      'health facility', 'interpersonal aspects of care' and 'access to services' were
      0.72, 0.64, 0.72 and 0.33, respectively. Respondents were positive on items
      related to the dimensions 'interpersonal aspects of care' and 'access to
      services', but negative on the dimensions 'health care delivery' and 'health
      facility'. The maternity status of clients was found to influence the perceived
      quality of maternity services. CONCLUSIONS: The feasibility, reliability and
      validity of the instrument were established in the context of rural Vietnam. Its
      application in evaluating other health care programmes should be an important
      follow-up action for the Vietnamese government.

PMID- 15557355
TI  - The Patient Experiences Questionnaire: development, validity and reliability.
AB  - OBJECTIVE: . To describe the development of the Patient Experiences Questionnaire
      (PEQ) and to evaluate reliability and validity of constructed summed rating
      scales. DESIGN: Literature review, focus groups and pilot surveys. Two national
      cross-sectional studies performed in 1996 and 1998. SETTING: Two postal surveys
      in a national sample of 14 hospitals stratified by geographical region and
      hospital size. Subjects. Patients consecutively discharged from surgical wards
      and wards of internal medicine. The surveys included 36 845 patients and 19 578
      responded (53%). RESULTS: We constructed 10 summed rating scales based on factor
      analysis and theoretical considerations: Information on future complaints,
      Nursing services, Communication, Information examinations, Contact with next-of
      kin, Doctor services, Hospital and equipment, Information medication,
      Organization and General satisfaction. Eight scales had a Cronbach alpha
      coefficient of >0.70, the remaining two were >0.60. Repeatability was >0.70 for
      five scales and >0.60 for the remaining scales. CONCLUSIONS: The PEQ is a self
      report instrument covering the most important subjects of interest to hospital
      patients. Results are presented as 10 scales with good validity and reliability.
      It emphasizes practicability and comprehensibility while at the same time
      providing sufficient information about domains applicable to most patients
      admitted to medical and surgical wards.

PMID- 15557356
TI  - Experiences of elderly patients regarding independent community living after
      discharge from hospital: a longitudinal study.
AB  - OBJECTIVE: To describe the reported experiences of elderly patients regarding
      their transition from an acute hospital to independent community living. DESIGN:
      Observational longitudinal study based on semi-structured interviews conducted
      monthly for 6 months following discharge from hospital. SETTING: Four South
      Australian acute hospitals. Patients. One hundred elderly patients who faced a
      long-term change in health status and/or in their ability to manage practical
      aspects of daily living. MAIN OUTCOME MEASURES: Experiences in managing change in
      health status, social circumstances and independent community living. RESULTS:
      Few patients believed that discharge plans made in hospital had assisted their
      return to independent community living. Discharge planning addressed mainly
      formal health services rather than practical aspects of daily living. Many
      patients implemented innovative solutions when formal services were unavailable
      or inadequate. Pain, tiredness, loss of mobility, and grief over loss of previous
      abilities were frequent, long lasting sequelae to illness, and few discharge
      plans prepared patients to deal with this. CONCLUSIONS: Elderly patients who have
      left hospital to face a permanent change in health status often regret that they
      have not been better prepared for what lies ahead in terms of more specific
      information about their condition, linked with practical discharge plans that
      prepare them for their period of convalescence. We suggest that the underlying
      problem is a disjunction between the multiple systems involved in hospital
      discharge planning, primary medical care, disability-oriented community health
      services, and informal community services.

PMID- 15557357
TI  - Cholecystectomy: costs and health-related quality of life: a comparison of two
      techniques.
AB  - BACKGROUND: Outcomes of previous health economic evaluations comparing
      minilaparotomy cholecystectomy and laparoscopic cholecystectomy have been
      inconsistent. OBJECTIVE: To compare costs for minilaparotomy cholecystectomy and
      laparoscopic cholecystectomy and to study changes in quality of life induced by
      these operations. DESIGN: Single-blind, randomized controlled trial, run from 1
      March 1997 to 30 April 1999. SETTING: One university hospital and four non
      university hospitals in Sweden. MAIN MEASURE: : Cost and perceived health
      estimation according to the global quality of life instrument EuroQol-5D.
      RESULTS: Of 1719 cholecystectomy patients at five centres, 724 entered the trial
      and were treated with minilaparotomy cholecystectomy or laparoscopic
      cholecystectomy, 362 in each group. Total health care costs were less for
      minilaparotomy cholecystectomy than for laparoscopic cholecystectomy (median
      values US$2428 for minilaparotomy cholecystectomy versus US$2613 or US$3006 for
      laparoscopic cholecystectomy with 100 operations per year and reusable trocars or
      50 operations per year and disposable trocars, respectively). There was no
      significant difference in total costs (including costs due to loss of production)
      between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with 100
      operations per year and reusable trocars in laparoscopic cholecystectomy (US$3731
      versus US$3649, respectively). However, in calculations assuming 50 operations
      per year and disposable trocars in laparoscopic cholecystectomy, this technique
      was more expensive than minilaparotomy cholecystectomy (US$4042 versus US$3731).
      Health-related quality of life was slightly but significantly lower for the
      minilaparotomy cholecystectomy group 1 week after surgery. One month and 1 year
      postoperatively no difference between the randomized groups was found.
      CONCLUSION: Total costs did not differ between minilaparotomy cholecystectomy and
      laparoscopic cholecystectomy with high-volume surgery and disposable trocars,
      whereas laparoscopic cholecystectomy was more expensive with fewer operations and
      disposable trocars. The gain in health-related quality of life with laparoscopic
      cholecystectomy compared with minilaparotomy cholecystectomy was small and of
      limited duration.

PMID- 15557358
TI  - Family satisfaction with nursing facility care.
AB  - BACKGROUND: We present the psychometric properties of our nursing facility family
      satisfaction questionnaire (NF-FSQ), and the steps used to develop this
      instrument. METHODS: Family members from 14 nursing facilities in Pennsylvania
      were mailed the NF-FSQ. Factor analyses were used to test the extent to which the
      items in each domain represented the same underlying construct. To further report
      the applied psychometric properties of the instrument we used the completeness of
      data, score distributions, item-scale consistency and reliability of domain
      scores. RESULTS: Of the 550 surveys mailed, 387 usable surveys were returned (70%
      response rate). Factor analyses show that the items were representative of the
      underlying factors. The percentage of family members not providing responses for
      each question was low, and varied from 1.0% to 3.4%. The floor and ceiling
      effects of the responses for each of the 20 questions were low. The item-scale
      internal consistency analyses determined that the correlation of items within
      indexes were higher than those with other indexes. Cronbach's alphas for the
      domains were all higher than usually recommended levels. CONCLUSIONS: We believe
      we have produced a short, psychometrically sound family member satisfaction
      instrument for use in nursing homes. We also show that response rates from family
      members can be very high.

PMID- 15557359
TI  - Doctor and nurse perception of inter-professional co-operation in hospitals.
AB  - OBJECTIVE: To explore doctor and nurse perception of inter-professional co
      operation in hospitals; discuss professional differences as reflections of
      cultural diversity in the perspective of quality improvement. DESIGN: Cross
      sectional survey data from a stratified sample of 15 Norwegian hospitals,
      September 1998: 551 doctors and 2050 nurses at medical and surgical wards.
      Measures. Doctor and nurse evaluation of their inter-professional co-operation
      was mapped. Logistic regression models predicting their satisfaction were
      compared. RESULTS: Doctors were significantly more often than nurses satisfied
      with the inter-professional co-operation of the two groups. Satisfaction with
      inter-professional co-operation was predicted by a number of work situation
      variables. Some of them contribute differently to doctor and nurse satisfaction.
      CONCLUSIONS: Doctors and nurses not only evaluate their inter-professional co
      operation differently, they also appear to define the concept in different ways.
      Hospital managers should include an understanding of this cultural diversity into
      the basis of their quality improvement efforts.

PMID- 15557360
TI  - Lessons from a patient partnership intervention to prevent adverse drug events.
AB  - BACKGROUND: Patient safety 'best practices' that call for patient participation
      to prevent adverse drug events have not been rigorously evaluated. OBJECTIVE: To
      consider lessons learned from a patient partnership intervention to prevent
      adverse drug events among medical in-patients. DESIGN: Prospective randomized,
      controlled pilot trial. SETTING: Boston teaching hospital. Patients. Two hundred
      and nine adult in-patients on a general medicine unit. INTERVENTION: Intervention
      patients (n = 107) received drug safety information and their medication list;
      controls (n = 102) received drug safety information only. Measurements. Adverse
      drug events and close-call drug errors were identified using chart review and
      incident reports from nurses, pharmacists, and physicians. Patients and
      clinicians were surveyed about the intervention. RESULTS: In 1053 patient-days at
      risk, 11 patients experienced 12 adverse drug events and 16 patients experienced
      18 close calls. There was a non-significant difference between intervention
      patients and controls in survey responses and in the adverse drug event rate
      (8.4% versus 2.9%, P = 0.12) and close-call rate (7.5% versus 9.8%, P = 0.57).
      Eleven percent of patients were aware of drug-related mistakes during the
      hospitalization. Among nurse respondents, 29% indicated that at least one
      medication error was prevented when a patient or family member identified a
      problem. CONCLUSION: Partnering with in-patients to prevent adverse drug events
      is a promising strategy but requires further study to document its efficacy.

PMID- 15557361
TI  - The informationist: a prospective uncontrolled study.
AB  - OBJECTIVE: To determine whether doctors in an Australian tertiary hospital would
      use an informationist service, and to identify how the service would influence
      care. DESIGN: A prospective uncontrolled pilot study July 2002-January 2003.
      SETTING: A teaching hospital in South Australia. STUDY PARTICIPANTS: Fourteen
      doctors working in the selected units. INTERVENTION: An informationist attended
      specified medical in-patient ward rounds and clinical meetings in the Respiratory
      Medicine, Sleep Disorders, and Rheumatology units. Main outcomes measures.
      Clinician self-assessed impact of information on a range of outcomes relating to
      clinical decision-making, clinician education, and avoidance of adverse events.
      RESULTS: In 23 weeks, 52 questions were generated by nine of 14 eligible doctors.
      Forty-eight of 52 (92%) feedback forms were completed, indicating an average of
      5.7 impacted outcomes per response. Twenty-five of 48 (52%) provided new
      information to doctors, and 24/48 (50%) provided at least some information that
      could be used immediately. Most common contributions of the service to patient
      care were revision of treatment plan (21/48, 44%) and confirmation of proposed
      therapy (18/48, 38%). Thirteen of 48 (27%) contributed to avoiding adverse
      events, and 10/48 (21%) contributed to avoiding additional tests and procedures.
      Eleven of 11 (100%) doctors who used the service assessed that it contributed or
      probably contributed to their professional development, with 8/10 (80%)
      indicating a similar impact on improving clinical outcomes. CONCLUSION: Medical
      staff will use an informationist service, which contributes substantially to a
      multiplicity of outcomes relating to medical decision-making, clinician
      education, and clinical outcomes.

PMID- 15557362
TI  - Influence of health insurance status on inclusion of HER-2/neu testing in the
      diagnostic workup of breast cancer patients.
AB  - OBJECTIVE: . To assess the prevalence of HER-2/neu testing in a community-based
      health care system shortly after the approval of several laboratory kits for HER
      2/neu testing for diagnostic purposes by the US Food and Drug Administration and
      to discern the best discriminating variables for inclusion of the test in the
      diagnostic workup of breast cancer patients. DESIGN: A retrospective cross
      sectional study was designed to analyze data for the period beginning 1 January
      1999 and ending 31 December 2000. SETTING: Henry Ford Health System, the largest
      health care system in southeastern Michigan, is a comprehensive, self-contained
      system. STUDY PARTICIPANTS: Four hundred and fifty-one women diagnosed with
      primary invasive breast cancers were consecutively sampled from the tumor
      registry of the Henry Ford Health System. RESULTS: The proportion of women tested
      for HER-2/neu increased by 2-fold during year 2 of the observation. Absence of
      estrogen receptors (OR = 1.96, 95% CI 1.15-3.21), physicians with specialty in
      surgery (OR = 6.21, 95% CI 2.88-13.33, P = 0.0001), and having a capitated
      insurance (OR = 1.59, 95% CI 1.06-2.44, P = 0.027) were associated with HER-2/neu
      testing. CONCLUSION: Absence of estrogen receptors was the only pathological
      characteristic associated with HER-2/neu testing. The effect of specialization in
      surgery on the increased likelihood of HER-2/neu testing can be explained mostly
      by the 'patient volume effect'. The observed disparity in the delivery of
      innovative diagnostic approaches to cancer patients was influenced by the type of
      health insurance. Implementation of institutional policies can improve in
      providing universal quality of care for all patients regardless of their health
      insurance.

PMID- 15557363
TI  - Childhood adiposity as a predictor of cardiac mass in adulthood: the Bogalusa
      Heart Study.
AB  - BACKGROUND: The association between left ventricular hypertrophy, an independent
      predictor of cardiovascular (CV) morbidity and mortality, and CV risk factors has
      been well documented in childhood and in adulthood. However, information on the
      relationship between left ventricular mass (LVM) in adults and longitudinal
      measurements of CV risk factors from childhood to adulthood is limited. METHODS
      AND RESULTS: LVM was obtained with 2D M-mode echocardiography in a community
      based sample of 467 young adults (71% white and 29% black) aged 20 to 38 years
      who were examined an average of 6 times for CV risk factors from childhood to
      adulthood. The average follow-up period was 21.5 years. The cumulative burden of
      each risk factor was calculated as the area under the curve for each individual.
      Compared with whites, blacks had greater LVM (indexed to height(2.7); P<0.05). In
      multiple regression analyses, adiposity (measured as body mass index) in
      childhood, adiposity and systolic blood pressure in adulthood, and the cumulative
      burden of adiposity and systolic blood pressure from childhood to adulthood were
      significant predictors of LVM index in young adults. CONCLUSIONS: These
      observations, by showing that adiposity beginning in childhood is a consistent
      predictor of LVM in young adults, underscore the importance of obesity in the
      development of left ventricular hypertrophy and the need for early prevention.

PMID- 15557364
TI  - Control of plasma nitric oxide bioactivity by perfluorocarbons: physiological
      mechanisms and clinical implications.
AB  - BACKGROUND: Perfluorocarbons (PFCs) are promising blood substitutes because of
      their chemical inertness and unparalleled ability to transport and upload O2 and
      CO2. Here, we report that PFC emulsions also efficiently absorb and transport
      nitric oxide (NO). METHODS AND RESULTS: Accumulation of NO and O2 in PFC micelles
      results in rapid NO oxidation and generation of reactive NO(x) species. Such
      micellar catalysis of NO oxidation leads to formation of vasoactive S
      nitrosothiols (RSNO) in vitro and in vivo as detected electrochemically. The
      efficiency of PFC-mediated S-nitrosation depends on the amount of PFC in aqueous
      solution. The optimal PFC concentration that produced the maximum level of RSNO
      was approximately 1% (vol/vol). Larger PFC amounts were progressively less
      efficient in generating RSNO and functioned simply as NO sink. These results
      explain the characteristic hemodynamic effects of PFCs. Intravenous bolus
      application of PFC (0.14 g/kg, approximately 1% vol/vol) to Wistar-Kyoto rats
      decreased mean arterial pressure significantly (-10 mm Hg over 40 minutes). PFC
      induced hypotension could be further stimulated (-17 mm Hg over 140 minutes) by
      exogenous thiols (cysteine and glutathione). In contrast, a larger amount of PFC
      (1 g/kg, approximately 7% vol/vol) exhibited a strong hypertensive effect (11 mm
      Hg over 40 minutes). CONCLUSIONS: The present study reveals a physiologically
      significant pool of endogenous plasma NO and underscores the crucial role of the
      circulating hydrophobic phase in modulating its bioactivity. The results also
      establish PFC as a conceptually new pharmacological tool for various
      cardiovascular complications associated with NO imbalance.

PMID- 15557365
TI  - Involvement of metalloproteinases 2/9 in epidermal growth factor receptor
      transactivation in pressure-induced myogenic tone in mouse mesenteric resistance
      arteries.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) transactivation is a mediator
      of angiotensin II (Ang II) signaling in cultured vascular smooth muscle cells
      isolated from large arteries. The present study used mouse mesenteric resistance
      arteries (MRAs) to investigate the role of EGFR transactivation under pressure
      induced myogenic tone (MT). METHODS AND RESULTS: Isolated MRAs were mounted in an
      arteriograph and stimulated by 25 to 125 mm Hg or with Ang II and KCl. Stepwise
      increases in pressure resulted in MT development associated with increased EGFR
      phosphorylation and release of heparin-binding EGF (HB-EGF), a membrane-bound
      growth factor that is shed on cleavage by metalloproteinases. EGF (50 ng/mL)
      potentiated MT (59+/-1% to 51+/-0.6% of passive diameter at 75 mm Hg).
      Pretreatment with the EGFR inhibitors AG1478 (5 micromol/L) or PD153035 (1
      micromol/L) significantly decreased MT. However, EGFR inhibitors had no effect on
      Ang II- and KCl-induced contraction. MT was potentiated by HB-EGF, 50 ng/mL,
      which is bound to the cell membrane and released on cleavage by
      metalloproteinases. Neutralizing HB-EGF antibodies or heparin treatment to
      sequester HB-EGF resulted in significant inhibition of pressure-induced MT. MT
      increased matrix metalloproteinase (MMP) 2 and MMP-9 gelatinase activity assessed
      by zymography, and specific MMP 2/9 inhibitors significantly decreased MT.
      CONCLUSIONS: These novel findings suggest that the mechanism of pressure-induced
      MT involves metalloproteinases 2/9 activation with subsequent HB-EGF release and
      EGFR transactivation.

PMID- 15557366
TI  - Role for the Kunitz-3 domain of tissue factor pathway inhibitor-alpha in cell
      surface binding.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI)-alpha, a key regulator of
      tissue factor-induced coagulation, contains 3 tandem Kunitz-type inhibitory
      domains. Kunitz-1 binds and inhibits factor VIIa in the factor VIIa/tissue factor
      complex, and Kunitz-2 binds and inhibits factor Xa. The role of the Kunitz-3
      domain of TFPI-alpha, however, has remained an enigma. METHODS AND RESULTS: To
      determine the structures within TFPI-alpha involved in its binding to cell
      surface, altered forms of TFPI-alpha were expressed in C127 (mouse mammary)
      cells: C-terminal truncated forms TFPI-alpha (252), TFPI-alpha (242), and TFPI
      alpha (181), which also lacks the third Kunitz domain (K3); TFPI-alpha (desK3),
      which lacks only the K3 domain; and TFPI-alpha (R199L), in which the putative P1
      site in K3 is changed from arginine to leucine. By flow cytometry (fluorescence
      activated cell sorting), the altered forms 252, 242, and R199L showed
      significantly reduced binding, whereas the forms 181 and desK3 completely failed
      to bind to the cell surface. Transient expression of WT-, desK3-, and K3/K2-TFPI
      alpha (in which K3 is replaced with K2) in another cell line (b-end3, mouse
      endothelial) produced comparable results. Exogenously added C-terminal truncated
      and R199L forms of TFPI-alpha bound poorly and desK3 did not bind at all to the
      surface of ECV304 cells in which TFPI-alpha expression had been "knocked down" by
      RNA interference. CONCLUSIONS: Optimal cell binding of endogenously expressed
      TFPI-alpha requires its K3 and C-terminal domains, and within the K3 domain, the
      P1 (R199) residue plays an important role. Thus, one role of the K3 domain
      involves the cell surface localization of TFPI-alpha.

PMID- 15557367
TI  - Nonuniform strut distribution correlates with more neointimal hyperplasia after
      sirolimus-eluting stent implantation.
AB  - BACKGROUND: Little is known about causes of intimal hyperplasia (IH) after
      sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: Intravascular
      ultrasound was performed in 24 lesions with intra-SES restenosis and a comparison
      group of 25 nonrestenotic SESs. To assess stent strut distribution, the maximum
      interstrut angle was measured with a protractor centered on the stent, and the
      visible struts were counted and normalized for the number of stent cells. In SES
      restenosis patients, minimum lumen site was compared with image slices 2.5, 5.0,
      7.5, and 10.0 mm proximal and distal to this site. The minimum lumen site had a
      smaller IVUS lumen area at follow-up (2.7+/-0.9 versus 6.2+/-1.9 mm2; P<0.01),
      larger maximum interstrut angle (135+/-39 degrees versus 72+/-23 degrees;
      P<0.01), larger IH area (3.4+/-1.5 versus 0.6+/-1.1 mm2; P<0.01) and thickness
      (0.7+/-0.3 versus 0.1+/-0.2 mm; P<0.01) at maximum interstrut angle, and fewer
      stent struts (4.9+/-1.0 versus 6.0+/-0.5; P<0.01) even when normalized for the
      number of stent cells (0.78+/-0.15 versus 0.97+/-0.07; P<0.01). Compared with
      nonrestenotic SES, the restenosis lesions also had a smaller minimal lumen area,
      larger IH area, thicker IH at maximum interstrut angle, fewer stent struts, and
      larger maximum interstrut angle. Multivariate analysis identified the number of
      visualized stent struts normalized for the number of stent cells and maximum
      interstrut angle as the only independent IVUS predictor of IH cross-sectional
      area (P<0.01 and P<0.01), minimum lumen area (P<0.01 and P<0.01), and IH
      thickness (P<0.01 and P<0.01). CONCLUSIONS: The number and distribution of stent
      struts affect the amount of neointima after SES implantation.

PMID- 15557368
TI  - Functional interplay between the macrophage scavenger receptor class B type I and
      pitavastatin (NK-104).
AB  - BACKGROUND: Scavenger receptor class B type I (SR-BI), a receptor for high
      density lipoprotein (HDL), plays an important role in the bidirectional
      cholesterol exchange between cells and HDL particles and the atherosclerotic
      lesion development. Enhancement of SR-BI expression significantly reduces,
      whereas lack of SR-BI expression accelerates, the atherosclerotic lesion
      development in proatherogenic mice. Statins, a class of inhibitors for 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase, significantly suppress de novo
      cholesterol synthesis and reduce the incidence of coronary heart disease. Statins
      also display multiple pleiotropic effects independently of cholesterol synthesis
      in the vascular cells. Here, we investigated the effects of pitavastatin (NK
      104), a newly synthesized statin, on macrophage SR-BI expression. METHODS AND
      RESULTS: We found that pitavastatin significantly increased SR-BI mRNA and
      protein expression in a macrophage cell line in a concentration- and time
      dependent manner. It also increased SR-BI expression in both mouse peritoneal and
      human monocyte-derived macrophages. Associated with increased SR-BI expression,
      pitavastatin enhanced macrophage HDL binding, uptake of [14C]cholesteryl
      oleate/HDL, and efflux of [3H]cholesterol to HDL. Pitavastatin abolished the
      inhibition of macrophage SR-BI expression by cholesterol biosynthetic
      intermediates. It also restored SR-BI expression inhibited by lipopolysaccharide
      and tumor necrosis factor-alpha through its inactivation of the transcription
      factor nuclear factor-kappaB. CONCLUSIONS: Our data demonstrate that pitavastatin
      can stimulate macrophage SR-BI expression by reduction of cholesterol
      biosynthetic intermediates and antiinflammatory action and suggest additional
      pleiotropic effects of statins by which they may reduce the incidence of coronary
      heart disease.

PMID- 15557369
TI  - Identification of a gene expression profile that differentiates between ischemic
      and nonischemic cardiomyopathy.
AB  - BACKGROUND: Gene expression profiling refines diagnostic and prognostic
      assessment in oncology but has not yet been applied to myocardial diseases. We
      hypothesized that gene expression differentiates ischemic and nonischemic
      cardiomyopathy, demonstrating that gene expression profiling by clinical
      parameters is feasible in cardiology. METHODS AND RESULTS: Affymetrix U133A
      microarrays of 48 myocardial samples from Johns Hopkins Hospital (JHH) and the
      University of Minnesota (UM) obtained (1) at transplantation or left ventricular
      assist device (LVAD) placement (end-stage; n=25), (2) after LVAD support (post
      LVAD; n=16), and (3) from newly diagnosed patients (biopsy; n=7) were analyzed
      with prediction analysis of microarrays. A training set was used to develop the
      profile and test sets to validate the accuracy of the profile. An etiology
      prediction profile developed in end-stage JHH samples was tested in independent
      samples from both JHH and UM with 100% sensitivity and 100% specificity in end
      stage samples and 33% sensitivity and 100% specificity in both post-LVAD and
      biopsy samples. The overall sensitivity was 89% (95% CI 75% to 100%), and
      specificity was 89% (95% CI 60% to 100%) over 210 random partitions of end-stage
      samples into training and test sets. Age, gender, and hemodynamic differences did
      not affect the profile's accuracy in stratified analyses. Select gene expression
      was confirmed with quantitative polymerase chain reaction. CONCLUSIONS: Gene
      expression profiling accurately predicts cardiomyopathy etiology, is
      generalizable to samples from separate institutions, is specific to disease
      stage, and is unaffected by differences in clinical characteristics. This
      strongly supports ongoing efforts to incorporate expression profiling-based
      biomarkers in determining prognosis and response to therapy in heart failure.

PMID- 15557370
TI  - Short-term effects of right-left heart sequential cardiac resynchronization in
      patients with heart failure, chronic atrial fibrillation, and atrioventricular
      nodal block.
AB  - BACKGROUND: Single-site ventricular pacing in patients with heart failure, atrial
      fibrillation, and severe atrioventricular (AV) nodal block risks the generation
      of discoordinate contraction. Whether altering the site of stimulation can offset
      this detrimental effect and what role sequential right ventricular-left
      ventricular (RV-LV) stimulation might play in such patients remain unknown.
      METHODS AND RESULTS: Nine subjects with heart failure (ejection fraction, 14% to
      30%), atrial fibrillation, and AV block were studied by pressure-volume analysis.
      Ventricular stimulation was applied to the RV (apex and outflow tract), LV free
      wall, and biventricular (BiV) at 80 and 120 bpm. BiV improved systolic function
      more than either site alone (dP/dt(max), 810+/-83, 924+/-98, 983+/-102 mm Hg/s
      for RV, LV, BiV, respectively; P<0.05), although LV pacing was significantly
      better than RV pacing. However, only BiV improved diastolic function (isovolumic
      relaxation) over RV or LV alone. Similar results were obtained for both heart
      rates. RV pacing site did not alter the BiV effect, and concomitant stimulation
      of both RV sites did not improve function over each alone. Finally, varying RV-LV
      delay revealed optimal responses with simultaneous pacing. CONCLUSIONS:
      Simultaneous BiV pacing acutely enhances both systolic and diastolic function
      over single-site RV or LV pacing in congestive heart failure patients with atrial
      fibrillation and advanced AV block. Sequential RV-LV stimulation offers minimal
      benefit on average and should perhaps be considered only in targeted subsets such
      as nonresponding patients.

PMID- 15557371
TI  - One-year coronary bypass graft patency: a randomized comparison between off-pump
      and on-pump surgery angiographic results of the PRAGUE-4 trial.
AB  - BACKGROUND: Off-pump coronary bypass surgery has become a widely used technique
      during recent years. However, limited data are available with regard to 1-year
      patency of bypass grafts implanted on the beating heart in unselected consecutive
      bypass surgery candidates. The aim of this study was to compare 1-year
      angiographic patency of bypass grafts done on the beating heart (off pump) with
      those done classically (on pump). METHODS AND RESULTS: The PRAGUE-4 trial
      randomized 400 consecutive nonselected cardiac surgery candidates into group A
      (on pump; n=192) and group B (off pump; n=208). One-year follow-up coronary
      angiography was done in 255 patients. The arterial graft patency after 1 year was
      91% in both groups. Saphenous graft patency was 59% (on pump) versus 49% (off
      pump; P=NS). Saphenous graft patency per patient was lower in the off-pump group:
      0.7 patent anastomosis per patient versus 1.1 patent anastomosis in the on-pump
      group (P<0.01). There were 46% on-pump patients with all grafts patent versus 52%
      off-pump patients (P=NS). Grafts anastomosed distally to collateralized chronic
      total occlusions of native coronary arteries remained patent in 100% on the left
      anterior descending artery compared with 23% on other arteries (P<0.0001).
      CONCLUSIONS: The patency of arterial coronary bypass grafts done on the beating
      heart is excellent and equal to grafts done on pump. The off-pump procedure in
      the unselected patient population results in fewer patent saphenous grafts per
      patient.

PMID- 15557372
TI  - Prognostic value of anxiety and depression in patients with chronic heart
      failure.
AB  - BACKGROUND: Anxiety is often present with depression and may be one of its
      manifestations. Although the adverse effects of depression in patients with
      chronic heart failure (CHF) have been well studied, the relation between anxiety
      and CHF prognosis has not been addressed. In a secondary analysis of data
      collected for a published study of depression and prognosis in patients with CHF,
      we examined the relations among anxiety, depression, and prognosis. METHODS AND
      RESULTS: We measured symptoms of anxiety with the Spielberger State-Trait Anxiety
      Inventory (STAI) scale and symptoms of depression with the Beck Depression
      Inventory (BDI) scale in 291 patients with CHF hospitalized as a result of
      cardiac events. We followed up these patients for all-cause mortality over 1
      year. The mean scores for state anxiety (State-A) and trait anxiety (Trait-A)
      were identical at 33.5; the mean BDI score was 8.7+/-7.6. State-A and Trait-A
      scores correlated highly with each other (r=0.85; P<0.01) and with BDI score
      (State-A, r=0.52; Trait-A, r=0.59; P<0.01). Cox proportional-hazards model with
      and without confounding variables showed no relation between State-A or Trait-A
      and 1-year mortality. BDI scores, however, significantly predicted increased
      mortality during 1-year follow-up (hazard ratio, 1.04 for each 1-unit increase;
      P<0.01). CONCLUSIONS: Although anxiety and depression are highly correlated in
      CHF patients, depression alone predicts a significantly worse prognosis for these
      patients.

PMID- 15557373
TI  - Impact of interleukin-6 on plaque development and morphology in experimental
      atherosclerosis.
AB  - BACKGROUND: Vascular lipid accumulation and inflammation are hallmarks of
      atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of
      inflammation, ie, interleukin (IL)-6, are elevated in patients with acute
      coronary syndromes and may contribute to the exacerbation of atherosclerosis.
      METHODS AND RESULTS: To assess the role of IL-6 in atherosclerosis, ApoE-/--IL-6
      /- double-knockout mice were generated, fed a normal chow diet, and housed for
      53+/-4 weeks. Mortality and blood pressure were unaltered. However, serum
      cholesterol levels and subsequent atherosclerotic lesion formation (oil red O
      stain) were significantly increased in ApoE-/--IL-6-/- mice compared with ApoE-/
      , wild-type (WT), and IL-6-/- mice. Plaques of ApoE-/--IL-6-/- mice showed
      significantly reduced transcript and protein levels of matrix metalloproteinase
      9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase
      (by reverse transcriptase-polymerase chain reaction and immunohistochemistry).
      Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into
      the atherosclerotic lesion was significantly reduced in ApoE-/--IL-6-/- mice. The
      transcript and serum protein (ELISA) levels of IL-10 were significantly reduced.
      CONCLUSIONS: Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque
      formation in ApoEK-/--IL-6-/- mice and leads to maladaptive vascular
      developmental processes. These observations are consistent with the notion that
      baseline levels of IL-6 are required to modulate lipid homeostasis, vascular
      remodeling, and plaque inflammation in atherosclerosis.

PMID- 15557374
TI  - Spotty calcification typifies the culprit plaque in patients with acute
      myocardial infarction: an intravascular ultrasound study.
AB  - BACKGROUND: Calcification is a common finding in human coronary arteries;
      however, the relationship between calcification patterns, plaque morphology, and
      patterns of remodeling of culprit lesions in a comparison of patients with acute
      coronary syndromes (ACS) and those with stable conditions has not been
      documented. METHODS AND RESULTS: Preinterventional intravascular ultrasound
      (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction
      (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris
      (SAP). The frequency of calcium deposits within an arc of less than 90 degrees
      for all calcium deposits was significantly different in culprit lesions of
      patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of
      calcium deposits within an arc of <90 degrees per patient was significantly
      higher in AMI than in SAP (P<0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8).
      Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001;
      mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients,
      the typical pattern was spotty calcification, associated with a fibrofatty plaque
      and positive remodeling. In ACS patients showing negative remodeling, no
      calcification was the most frequent observation. Conversely, SAP patients had the
      highest frequency of extensive calcification. CONCLUSIONS: Our observations show
      that IVUS allows the identification of vulnerable plaques in coronary arteries,
      not only by identifying a fibrofatty plaque and positive remodeling, but also by
      identifying a spotty pattern of calcification.

PMID- 15557375
TI  - Heat shock protein 70 confers cardiovascular protection during endotoxemia via
      inhibition of nuclear factor-kappaB activation and inducible nitric oxide
      synthase expression in the rostral ventrolateral medulla.
AB  - BACKGROUND: Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS)
      in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons
      are located, plays a pivotal role in the manifestation of fatal cardiovascular
      depression during endotoxemia. The iNOS gene is regulated transcriptionally by
      nuclear factor-kappaB (NF-kappaB) activation. The present study tested the
      hypothesis that heat shock protein 70 (HSP70) may confer protection against
      sepsis-induced circulatory fatality via inhibition of iNOS gene expression in the
      RVLM through prevention of NF-kappaB activation. METHODS AND RESULTS: Adult male
      Sprague-Dawley rats subjected to a brief hyperthermic heat shock (42 degrees C
      for 15 minutes) exhibited significant upregulation of HSP70 in the RVLM. Brief
      heat shock preconditioning also significantly suppressed iNOS mRNA or protein
      surge and alleviated hypotension, bradycardia, and reduction in neurogenic
      sympathetic vasomotor activity manifested during experimental endotoxemia induced
      by intravenous administration of Escherichia coli lipopolysaccharide. An increase
      in DNA binding activity and nuclear translocation of transcription factor NF
      kappaB were detected during endotoxemia. Heat shock preconditioning significantly
      decreased DNA binding activity of NF-kappaB, which was reversed by microinjection
      of an hsp70 antisense oligonucleotide bilaterally into the RVLM. Heat shock
      preconditioning also blocked inhibitory kappaB (IkappaB) kinase activity or
      degradation of IkappaB in the RVLM during endotoxemia. CONCLUSIONS: We conclude
      that HSP70 confers protection against sepsis-related circulatory fatality via
      inhibition of iNOS gene expression in the RVLM through prevention of NF-kappaB
      activation in cellular processes that include prevention of IkappaB kinase
      activation and inhibition of IkappaBalpha degradation.

PMID- 15557376
TI  - In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in
      rats after aortic stenosis.
AB  - BACKGROUND: Prolongation of the action potential duration (APD) and decreased
      transient outward K+ current (I(to)) have been consistently observed in cardiac
      hypertrophy. The relation between electrical remodeling and cardiac hypertrophy
      in vivo is unknown. METHODS AND RESULTS: We studied rat hearts subjected to
      pressure overload by surgical ascending aortic stenosis (AS) and simultaneously
      infected these hearts with an adenovirus carrying either the Kv4.3 gene
      (Ad.Kv4.3) or the beta-galactosidase gene (Ad.beta-gal). I(to) density was
      reduced and APD50 was prolonged (P<0.05) in AS rats compared with sham rats.
      Kv4.2 and Kv4.3 expressions were decreased by 58% and 51%, respectively (P<0.05).
      AS rats infected with Ad.beta-gal developed cardiac hypertrophy compared with
      sham rats, as assessed by cellular capacitance and heart weight-body weight
      ratio. Associated with the development of cardiac hypertrophy, the expression of
      calcineurin and its downstream transcription factor nuclear factor of activated T
      cells (NFAT) c1 was persistently increased by 47% and 36%, respectively (P<0.05)
      in AS myocytes infected with Ad.beta-gal compared with sham myocytes. In vivo
      gene transfer of Kv4.3 in AS rats was shown to increase Kv4.3 expression,
      increase I(to) density, and shorten APD50 by 1.6-fold, 5.3-fold, and 3.6-fold,
      respectively (P<0.05). Furthermore, AS rats infected with Ad.Kv4.3 showed
      significant reductions in calcineurin and NFAT expression. (P<0.05). CONCLUSIONS:
      Downregulation of I(to), APD prolongation, and cardiac hypertrophy occur early
      after AS, and in vivo gene transfer of Kv4.3 can restore these electrical
      parameters and abrogate the hypertrophic response via the calcineurin pathway.

PMID- 15557377
TI  - Intramyocyte detection of Epstein-Barr virus genome by laser capture
      microdissection in patients with inflammatory cardiomyopathy.
AB  - BACKGROUND: The causal role of Epstein-Barr virus (EBV) in inflammatory
      cardiomyopathy (IC) is still unclear, because this virus is present in latently
      infected circulating B lymphocytes in 90% of adults. Laser capture
      microdissection (LCM) has been applied on endomyocardial biopsy samples from
      patients with IC to assess the presence of EBV genome in separately dissected
      lymphocytes and myocytes. METHODS AND RESULTS: Among 142 patients with cardiac
      dilation and dysfunction and a histological and immunohistochemical diagnosis of
      myocarditis, 44 had a myocardial viral infection detected by polymerase chain
      reaction on frozen endomyocardial biopsy samples. In 9 of them, the virus
      detected was EBV. LCM was performed on 5-microm-thick paraffin sections of EBV
      infected hearts. Lymphocytes and myocytes were microdissected and analyzed
      separately by polymerase chain reaction analysis on DNA extracted from the
      collected cells. Blood and myocardial samples from patients with positive and
      negative serology for EBV were used as controls. EBV genome was detected in
      myocytes but not in infiltrating lymphocytes of patients, nor in myocardial
      samples from controls. Despite full conventional antifailure therapy, a
      progressive cardiac dilation and dysfunction was documented in patients with EBV
      related IC at a mean of 31+/-14 months of follow-up. CONCLUSIONS: Intramyocyte
      detection of EBV can be obtained by LCM in up to 6.3% of patients with IC. This
      supports a cytopathic EBV role and suggests the opportunity for an
      antiviral/immunomodulatory therapy.

PMID- 15557378
TI  - Coronary blood flow assessment after successful angioplasty for acute myocardial
      infarction predicts the risk of long-term cardiac events.
AB  - BACKGROUND: Analysis of coronary flow velocity (CFV) in the recanalized infarct
      related coronary artery (IRA) with a Doppler guidewire is useful for predicting
      recovery of regional left ventricular function, in-hospital complications, and
      survival. We postulated that the CFV pattern after IRA reperfusion for acute
      myocardial infarction (AMI) would predict long-term adverse cardiac events.
      METHODS AND RESULTS: Sixty-eight consecutive patients with a first AMI underwent
      CFV measurement with a Doppler guidewire after successful reopening of the IRA by
      coronary angioplasty. At the end of follow-up, 3.8+/-1.7 years after AMI, 44 of
      the 65 surviving patients (67.7%) were free of long-term cardiac events.
      Univariate analysis showed that the following factors were predictive of an end
      point combining cardiac death, recurrent MI, and congestive heart failure:
      hypertension, age > or =65 years, time from onset of chest pain to PTCA > or =6
      hours, peak creatine kinase >4000 IU/L, ejection fraction < or =50%, proximal
      left anterior descending artery occlusion, resting average peak velocity < or =10
      cm/s, average systolic peak velocity < or =5 cm/s, a rapid diastolic deceleration
      time (< or =600 ms), and early retrograde systolic flow. In the final
      multivariate model, only age > or =65 years (OR, 3.6; 95% CI, 1.1 to 11.8;
      P=0.03), time to PTCA > or =6 hours (OR, 2.9; 95% CI, 1.0 to 8.3; P=0.04), and a
      rapid diastolic deceleration time (OR, 5.4; 95% CI, 1.5 to 19.3; P=0.01) were
      independent predictors. CONCLUSIONS: The CFV pattern appears to be an accurate
      predictor of long-term cardiac events in patients having undergone successful
      reopening of the IRA after AMI, identifying a subset of at-risk patients.

PMID- 15557379
TI  - Assessment of myocardial viability by intracellular 23Na magnetic resonance
      imaging.
AB  - BACKGROUND: Because of rapid changes in myocardial intracellular Na+ (Na+(i))
      during ischemia and reperfusion (R), 23Na magnetic resonance imaging (MRI)
      appears to be an ideal diagnostic modality for early detection of myocardial
      ischemia and viability. So far, cardiac 23Na MRI data are limited and mostly
      concerned with imaging of total Na+. For proper interpretation, imaging of both
      Na+(i) and extracellular Na+ is essential. In this study, we tested whether
      Na+(i) imaging can be used to assess viability after low-flow (LF) ischemia.
      METHODS AND RESULTS: Isolated rat hearts were subjected to LF (1%, 2%, or 3% of
      control coronary flow) and R. A shift reagent was used to separate Na+(i) and
      extracellular Na+ resonances. Acquisition-weighted 23Na chemical shift imaging
      (CSI) was alternated with 23Na MR spectroscopy. Already during control perfusion,
      Na+(i) could be clearly seen on the images. Na+(i) image intensity increased with
      increasing severity of ischemia. During R, Na+(i) image intensity remained
      highest in 1% LF hearts. Not only did we find very good correlations between
      Na+(i) image intensity at end-R and end-diastolic pressure (R=0.85, P<0.001) and
      recovery of the rate-pressure product (R=-0.88, P<0.001) at end-R, but most
      interestingly, also Na+(i) image intensity at end-LF was well correlated with end
      diastolic pressure (R=0.78, P<0.01) and with recovery of the rate-pressure
      product (R=-0.81, P<0.01) at end-R. Furthermore, Na+(i) image intensity at end-LF
      was well correlated with creatine kinase release during R (R=0.79, P<0.05) as
      well as with infarct size (R=0.77, P<0.05). CONCLUSIONS: These data indicate that
      23Na CSI is a promising tool for the assessment of myocardial viability.

PMID- 15557380
TI  - Neuropsychological outcome after percutaneous coronary intervention or coronary
      artery bypass grafting: results from the Stent or Surgery (SoS) Trial.
AB  - BACKGROUND: Coronary artery bypass surgery (CABG) has been associated with a
      range of neurological and neuropsychological complications from stroke to
      cognitive problems such as memory and problem solving disturbance. However,
      little is known about the impact of percutaneous coronary intervention (PCI) on
      neuropsychological outcome. METHODS AND RESULTS: In the Stent or Surgery Trial
      (SoS), 988 patients were randomized in equal proportions between PCI supported by
      stent implantation and CABG. As a substudy of this trial, we undertook an
      evaluation of neurological and neuropsychological outcomes after intervention. A
      clinical examination and neuropsychological assessment consisting of 5 tests
      (Digit Span Forwards and Backwards, Visual Reproduction, Bourdon, and Block
      Design) were performed at baseline and 6 and 12 months after the procedure. A
      total of 145 patients were included in the substudy analysis: 77 in the PCI group
      and 68 in the CABG group. One patient in the PCI arm had a stroke. There was no
      significant difference between treatment groups at 6 and 12 months for any of the
      5 tests. The mean change from baseline was also similar in both groups.
      CONCLUSIONS: We were not able to demonstrate an important and significant
      difference in neuropsychological outcome in patients treated with different
      revascularization strategies. This important finding needs to be examined in
      further research.

PMID- 15557381
TI  - Prognostic impact of early ST-segment resolution in acute ST-elevation myocardial
      infarction.

PMID- 15557382
TI  - Images in cardiovascular medicine. Anomalous origin of the left coronary artery
      from the main pulmonary artery in adults: coronary collateralization at its best.

PMID- 15557383
TI  - Images in cardiovascular medicine. In-stent neointimal hyperplasia with 16-row
      multislice computed tomography coronary angiography.

PMID- 15557384
TI  - Regenerating more than muscle in muscular dystrophy.

PMID- 15557385
TI  - In vivo tracking of stem cells for clinical trials in cardiovascular disease.
AB  - Various stem cells hold promise for the treatment of human cardiovascular
      disease. Regardless of stem cell origin, future clinical trials will require that
      the location and number of such cells be tracked in vivo, over long periods of
      time. The problem of tracking small numbers of cells in the body is a difficult
      one, and an optimal solution does not yet exist. We review the many contrast
      agents and detectors that have been proposed for stem cell tracking during
      clinical trials, define the characteristics of an ideal imaging technology, and
      suggest future directions for research.

PMID- 15557386
TI  - Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and
      simplification of the Utstein templates for resuscitation registries: a statement
      for healthcare professionals from a task force of the International Liaison
      Committee on Resuscitation (American Heart Association, European Resuscitation
      Council, Australian Resuscitation Council, New Zealand Resuscitation Council,
      Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation,
      Resuscitation Councils of Southern Africa).
AB  - Outcome after cardiac arrest and cardiopulmonary resuscitation is dependent on
      critical interventions, particularly early defibrillation, effective chest
      compressions, and advanced life support. Utstein-style definitions and reporting
      templates have been used extensively in published studies of cardiac arrest,
      which has led to greater understanding of the elements of resuscitation practice
      and progress toward international consensus on science and resuscitation
      guidelines. Despite the development of Utstein templates to standardize research
      reports of cardiac arrest, international registries have yet to be developed. In
      April 2002, a task force of the International Liaison Committee on Resuscitation
      (ILCOR) met in Melbourne, Australia, to review worldwide experience with the
      Utstein definitions and reporting templates. The task force revised the core
      reporting template and definitions by consensus. Care was taken to build on
      previous definitions, changing data elements and operational definitions only on
      the basis of published data and experience derived from those registries that
      have used Utstein-style reporting. Attention was focused on decreasing the
      complexity of the existing templates and addressing logistical difficulties in
      collecting specific core and supplementary (ie, essential and desirable) data
      elements recommended by previous Utstein consensus conferences. Inconsistencies
      in terminology between in-hospital and out-of-hospital Utstein templates were
      also addressed. The task force produced a reporting tool for essential data that
      can be used for both quality improvement (registries) and research reports and
      that should be applicable to both adults and children. The revised and simplified
      template includes practical and succinct operational definitions. It is
      anticipated that the revised template will enable better and more accurate
      completion of all reports of cardiac arrest and resuscitation attempts. Problems
      with data definition, collection, linkage, confidentiality, management, and
      registry implementation are acknowledged and potential solutions offered. Uniform
      collection and tracking of registry data should enable better continuous quality
      improvement within every hospital, emergency medical services system, and
      community.

PMID- 15557387
TI  - Resurrection of uric acid as a causal risk factor in essential hypertension.

PMID- 15557388
TI  - Role of circulating S-nitrosothiols in control of blood pressure.

PMID- 15557389
TI  - Evaluation of concentric left ventricular geometry in humans: evidence for age
      related systematic underestimation.
AB  - There might be limitations in identifying concentric left ventricular (LV)
      geometry by ratio of diastolic posterior wall thickness (WT(p)) to cavity radius,
      defined as relative wall thickness (RWT(p)). This study has been designed to
      evaluate age effects on RWT(p). WT(p), mean of septal thickness and WT(p)
      (WT(m)), and cavity radius were cross-sectionally evaluated in 766 1- to 85-year
      old, normotensive, nonobese subjects and 331 hypertensive Italians (used as a
      test series). RWT(p) > or =0.43 defined "traditional" concentric LV geometry. The
      ratios WT(m)/radius (RWT(m)) and RWT(p) increased by 0.005 and 0.006 per year of
      age in the age stratum up to 17 years and by 0.002 in the older age stratum (18
      years or older; all P<0.0001). Thus, RWT(m) and RWT(p) were normalized to average
      age in both age strata (10 and 46 years) by age-specific regression coefficients.
      The 90th and 95th percentiles of age-normalized RWT(p) or RWT(m) were 0.40 and
      0.42 or 0.41 and 0.43, respectively, in adults and 0.36 and 0.39 or 0.36 and
      0.38, respectively in young subjects. In hypertensive subjects, traditional
      RWT(p) cutoff identified 74 subjects (22%) with concentric LV geometry; by 95th
      or 90th normal percentiles, normalized RWT(m) identified 112 (34%), or 149 (45%)
      subjects with concentric LV geometry, and normalized RWT(p) 29% and 39%,
      respectively (all P<0.0001 versus unadjusted RWT(p)). Thus, prevalence of
      concentric LV geometry increases with age-normalized RWT. Accordingly, we suggest
      that concentric LV hypertrophy be defined by coexistence of high LV mass with age
      normalized RWT(m) >0.41 or RWT(p) >0.40. Further studies are required to
      establish prognostic implications of our findings.

PMID- 15557390
TI  - Heritability of daytime ambulatory blood pressure in an extended twin design.
AB  - The present study estimated the genetic influences on ambulatory systolic and
      diastolic blood pressure, and on hypertensive status derived from ambulatory
      levels, in a family sample of 535 twins and 257 singleton siblings. This
      "extended twin design" was used to explicitly test the possibility that results
      obtained in singleton siblings are different from those obtained in twins. To
      examine the effects of excluding (medicated) hypertensive subjects, the genetic
      analyses were first performed under strict exclusion (medication and/or blood
      pressure >135/85 mm Hg), then without the medicated subjects, and, finally,
      without any exclusion. For the latter analysis, the untreated blood pressure
      values in subjects using antihypertensive medication were estimated by augmenting
      the observed blood pressure by the published efficacy of the specific
      antihypertensive medication used. No evidence was found for differential means,
      variances, or covariances of ambulatory blood pressure in singletons compared
      with twins. This indicates that estimates of heritability of ambulatory blood
      pressure from twin studies can be generalized to the singleton population.
      Heritability of hypertension, defined as a mean daytime blood pressure >135/85 mm
      Hg or antihypertensive medication use, was 61%. Genetic contribution to
      ambulatory blood pressure was highest when all subjects were included (systolic,
      44% to 57%; diastolic, 46% to 63%) and lowest under strict exclusion (systolic,
      32% to 50%; diastolic, 31% to 55%). We conclude that exclusion of (medicated)
      hypertensives removes part of the true genetic variance in ambulatory blood
      pressure.

PMID- 15557391
TI  - Low-molecular-weight heparin lowers the recurrence rate of preeclampsia and
      restores the physiological vascular changes in angiotensin-converting enzyme DD
      women.
AB  - Data from literature report that angiotensin-converting enzyme (ACE)
      insertion/deletion (I/D) polymorphism affects the recurrence of preeclampsia and
      that low-molecular-weight heparin (LMWH) prevents adverse outcomes in
      thrombophilic women. We investigated the effect of LMWH on the pregnancy outcome,
      on maternal blood pressure values, and on uteroplacental flow in ACE DD
      nonthrombophilic women with history of preeclampsia. Eighty nonthrombophilic ACE
      DD women were randomized in 2 groups: 41 treated with dalteparin 5000 IU/day and
      39 untreated (control group). Women underwent 24-hour automated blood pressure
      monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36 and
      transabdominal color flow/pulsed Doppler examination at weeks 16, 20, and 24.
      LMWH reduced the risk of clinical negative outcomes (74.1% reduction of
      preeclampsia and 77.5% reduction of fetal growth restriction) and the severity
      (88.3% reduction of early onset of preeclampsia and 86.4% reduction of early
      onset of fetal growth restriction). In treated women, the relative risk for
      preeclampsia was 0.26 (P=0.02), and the relative risk for fetal growth
      restriction was 0.14 (P<0.001). Systolic (P=0.002) and diastolic (P=0.002) blood
      pressures, as well as awake (P=0.04) and asleep (P=0.01) period values, and the
      resistance indexes of both uterine arteries (P=0.002) were lower in the treated
      group. LMWH reduces the recurrence of preeclampsia, of negative outcomes, and the
      resistance of uteroplacental flow, and also prevents maternal blood pressure
      increase in ACE DD homozygote women with a previous history of preeclampsia.

PMID- 15557393
TI  - Scientific freedom.

PMID- 15557392
TI  - Plasma sodium: ignored and underestimated.
AB  - Salt intake is a major regulator of blood pressure. There is evidence that those
      who develop high blood pressure have an underlying defect in the ability of the
      kidney to excrete salt. It has been suggested that this results in a greater
      tendency to retain sodium and an increased compensatory response that is
      responsible for the rise in blood pressure. There is also evidence suggesting
      that small increases in plasma sodium may directly affect blood pressure,
      independent of the associated expansion in extracellular volume. We reanalyzed 3
      types of studies of changing salt intake. (1) An acute and large reduction in
      salt intake from 350 mmol/d to 10 to 20 mmol/d for 5 days in hypertensives and
      normotensives was associated with a fall in plasma sodium of approximately 3
      mmol/L (P<0.001). (2) Progressive increases in salt intake from 10 to 250 mmol/d
      by a daily amount of 50 mmol in normotensives caused increases in plasma sodium
      (P<0.001). (3) Longer-term modest reduction in salt intake in hypertensives was
      studied in double-blind randomized crossover studies; 1 month of usual salt
      intake ( approximately 170 mmol/d) compared with reduced salt intake (
      approximately 100 mmol/d). There was a decrease in plasma sodium of 0.4+/-0.2
      mmol/L (P<0.05), which was weakly but significantly correlated with the fall in
      systolic blood pressure (r=0.18; P<0.05). These studies demonstrate that an
      increase or a decrease in salt intake causes changes in plasma sodium. Small
      changes in plasma sodium alter extracellular volume, which may influence blood
      pressure. Changes in plasma sodium may also affect blood pressure directly.

PMID- 15557394
TI  - Parallels between tooth development and repair: conserved molecular mechanisms
      following carious and dental injury.
AB  - The reparative mechanisms that operate following carious and traumatic dental
      injury are critical for pulp survival and involve a series of highly conserved
      processes. It appears that these processes share genetic programs-linked to
      cytoskeletal organization, cell movement, and differentiation-that occur
      throughout embryogenesis. Reactionary dentin is secreted by surviving
      odontoblasts in response to moderate stimuli, leading to an increase in metabolic
      activity. In severe injury, necrotic odontoblasts are replaced by other pulp
      cells, which are able to differentiate into odontoblast-like cells and produce a
      reparative dentin. This complex process requires the collaborative efforts of
      cells of different lineage. The behavior of each of the contributing cell types
      during the phases of proliferation, migration, and matrix synthesis as well as
      details of how growth factors control wound cell activities are beginning to
      emerge. In this review, we discuss what is known about the molecular mechanisms
      involved in dental repair.

PMID- 15557395
TI  - Tobacco-related-compound-induced nitrosative stress injury in the hamster cheek
      pouch.
AB  - The nitric oxide radical (*NO) released from tobacco-related compounds induces
      DNA damage, protein modifications, and cellular toxicity through the formation of
      peroxynitrite (ONOO-), the reaction product of *NO and the oxygen radical,
      superoxide. We hypothesize that tobacco-related compounds are cytotoxic and
      induce quantifiable DNA single-strand breaks in immortalized hamster cheek pouch
      (POII) cells, and that an amino acid marker of ONOO- injury, namely, 3
      nitrotyrosine (3-NT), is detectable in hamster cheek pouch tissues chronically
      exposed to these compounds. We observed a dose-dependent decrease in POII cell
      viability with increasing tobacco-related compound concentrations, as well as a
      dose-dependent increase in DNA strand breaks. Semi-quantitative
      immunohistochemistry showed intense 3-NT immunoreactivity in hamster tissues
      treated with tobacco-related compounds compared with controls (p < 0.005). Our
      results suggest that tobacco-related compounds, including nicotine, are
      genotoxic, and that 3-NT is a quantifiable marker of ONOO- damage in intact
      hamster cheek pouch tissues.

PMID- 15557396
TI  - Decreased mineral content in MMP-20 null mouse enamel is prominent during the
      maturation stage.
AB  - During enamel development, matrix metalloproteinase-20 (MMP-20, enamelysin) is
      expressed early during the secretory stage as the enamel thickens, and kallikrein
      4 (KLK-4, EMSP1) is expressed later during the maturation stage as the enamel
      hardens. Thus, we investigated whether the physical properties of the secretory
      /maturation-stage MMP-20 null enamel were significantly different from those of
      controls. We demonstrated that although, in relative terms, the weight percent of
      mature mineral in the MMP-20 null mouse enamel was only 7-16% less than that in
      controls, overall the enamel mineral was reduced by about 50%, and its hardness
      was decreased by 37%. Percent mineral content by weight was assessed at 3
      different developmental stages. Remarkably, the biggest difference in mineral
      content between MMP-20 null and controls occurred in the nearly mature enamel,
      when MMP-20 is normally no longer expressed. This suggests that MMP-20 acts
      either directly or indirectly to facilitate the removal of maturation-stage
      enamel proteins.

PMID- 15557397
TI  - TEGDMA modulates glutathione transferase P1 activity in gingival fibroblasts.
AB  - Dental resinous materials can contain large amounts (from 30 to 50%) of
      triethylene-glycol-dimethacrylate (TEGDMA). This compound leaches into aqueous
      media and is toxic to dental pulp, as well as to gingival fibroblasts in vitro.
      To elucidate the mechanism of TEGDMA toxicity, we investigated the effects on
      glutathione (GSH) level and glutathione transferase P1 (GSTP1) activity in
      cultured human gingival fibroblasts. TEGDMA cytotoxic concentrations (from 0.5 to
      2 mM) induced a depletion of GSH without formation of oxidized GSH (GSSG). In
      fibroblasts expressing the wild-type GSTP1, TEGDMA both inhibited and potentiated
      GSTP1 activity at high (IC50 = 1.1 mM) and low concentrations, respectively. In
      contrast, cells expressing the GSTP1 *A/*B variant showed a weak inhibition of
      GST activity only, associated with greater sensitivity to drug toxicity.
      Biochemical analysis of GSTP1 inhibition revealed that TEGDMA is a non
      competitive antagonist with respect to GSH and substrate. Thus, TEGDMA
      interference with GSH and GSTP1 activity may contribute to dental-resin-induced
      adverse effects.

PMID- 15557398
TI  - Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth
      movement.
AB  - Previously, we discovered that RANKL expression is induced in compressed
      periodontal ligament cells, and that this promotes osteoclastogenesis on the
      compression side in orthodontic tooth movement. We hypothesized that local OPG
      gene transfer to the periodontium would neutralize the RANKL activity induced by
      mechanical compressive force, thereby inhibiting osteoclastogenesis and
      diminishing tooth movement. The upper first molars of six-week-old male Wistar
      rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG
      expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of
      functional OPG protein was confirmed in vitro. The inactivated HVJ envelope
      vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the
      palatal periodontal tissue of upper first molars. When this local OPG gene
      transfer was performed, OPG production was induced, and osteoclastogenesis was
      inhibited. Local OPG gene transfer significantly diminished tooth movement. In
      this study, we report that OPG gene transfer to periodontal tissue inhibited
      RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.

PMID- 15557399
TI  - Progress of cell proliferation in striated muscle tissues during development of
      the mouse tongue.
AB  - The developmental stages of and places for the proliferation of tongue muscle
      cells have not yet been determined. To determine the stages of and places for
      proliferation between embryonic day (E) 9 and birth, we analyzed the expression
      of cyclin D1 mRNA and the immunolocalization for proliferating cell nuclear
      antigen (PCNA). The ratio of PCNA-positive nuclei to total nuclei (PCNA-labeling
      index) was obtained in the anterior, middle, and posterior regions. Cyclin D1
      mRNA was highly expressed between E11 and E13, but decreased thereafter until
      birth. The distribution of PCNA-positive cell nuclei was consistent with that of
      myogenic cells in the occipital somites at E9. The PCNA-labeling index was
      highest at E11, then decreased until birth without a significant difference among
      the 3 regions. These findings suggest that some tongue muscle progenitor cells
      begin proliferation in the occipital somites at E9, and that the proliferation in
      the whole tongue region occurred most actively between E11 and E13, then
      decreased until birth without regional differences.

PMID- 15557400
TI  - Wear and mechanical properties of nano-silica-fused whisker composites.
AB  - Resin composites must be improved if they are to overcome the high failure rates
      in large stress-bearing posterior restorations. This study aimed to improve wear
      resistance via nano-silica-fused whiskers. It was hypothesized that nano-silica
      fused whiskers would significantly improve composite mechanical properties and
      wear resistance. Nano-silicas were fused onto whiskers and incorporated into a
      resin at mass fractions of 0%-74%. Fracture toughness (mean +/- SD; n = 6) was
      2.92 +/- 0.14 MPa.m(1/2) for whisker composite with 74% fillers, higher than 1.13
      +/- 0.19 MPa.m(1/2) for a prosthetic control, and 0.95 +/- 0.11 MPa.m(1/2) for an
      inlay/onlay control (Tukey's at 0.95). A whisker composite with 74% fillers had a
      wear depth of 77.7 +/- 6.9 mum, less than 118.0 +/- 23.8 microm of an inlay/onlay
      control, and 172.5 +/- 15.4 microm of a prosthetic control (p < 0.05). Linear
      correlations were established between wear and hardness, modulus, strength, and
      toughness, with R = 0.95-0.97. Novel nano-silica-fused whisker composites
      possessed high toughness and wear resistance with smooth worn surfaces, and may
      be useful in large stress-bearing restorations.

PMID- 15557401
TI  - Epitope mapping of Porphyromonas gingivalis heat-shock protein and human heat
      shock protein in human atherosclerosis.
AB  - To identify T- and/or cross-reactive B-cell epitopes of P. gingivalis and human
      heat-shock protein (HSP)60 in atherosclerosis patients, we synthesized 104
      overlapping synthetic peptides spanning whole molecules of P. gingivalis HSP60
      and human HSP60, respectively. T-cell epitopes of P. gingivalis HSP were
      identified with the use of previously established P. gingivalis HSP-reactive T
      cell lines. B-cell epitopes of P. gingivalis HSP60 and human HSP60 were
      identified by the use of patients' sera. Anti-P. gingivalis, anti-P. gingivalis
      HSP60, or anti-human HSP60 IgG antibody titers were higher in the atherosclerosis
      patients compared with the healthy subjects. Five immunodominant peptides of P.
      gingivalis HSP60, identified as T-cell epitopes, were also found to be B-cell
      epitopes. Moreover, 6 cross-reactive B-cell epitopes of human HSP60 were
      identified. It was concluded that P. gingivalis HSP60 might be involved in the
      immunoregulatory process of atherosclerosis, with common T- and/or B-cell epitope
      specificities and with cross-reactivity with human HSP60.

PMID- 15557402
TI  - Localization of Porphyromonas gingivalis-carrying fimbriae in situ in human
      periodontal pockets.
AB  - Fimbriae, which are involved in adherence, constitute an important pathogenic
      factor of Porphyromonas gingivalis. In vivo, however, the distribution of P.
      gingivalis-carrying fimbriae is unknown. The localization of P. gingivalis
      carrying fimbriae was examined in situ. From 19 patients with severe
      periodontitis and P. gingivalis, we obtained 20 teeth with periodontal tissue
      attached, with and without immunolocalized fimbriae. Eleven teeth were subjected
      to light microscopy, 9 to electron microscopy. In 6 of the 11 samples examined,
      we detected positive reactions with an anti-P. gingivalis-fimbriae serum, located
      in the cementum-attached plaque area in the deep pocket zones. In the so-called
      'plaque-free zones', P. gingivalis-carrying fimbriae were immunocytochemically
      observed to reside in contact with the dental cuticle in 6 of the 9 samples
      examined. These findings suggest that P. gingivalis-carrying fimbriae are
      strongly related to adherence to the root surface at the bottoms of human
      periodontal pockets.

PMID- 15557403
TI  - Endurance during chewing in whiplash-associated disorders and TMD.
AB  - We have previously shown an association between neck injury and disturbed jaw
      function. This study tested the hypothesis of a relationship between neck injury
      and impaired endurance during chewing. Fifty patients with whiplash-associated
      disorders (WAD) were compared with 50 temporomandibular disorders (TMD) patients
      and 50 healthy subjects. Endurance was evaluated during unilateral chewing of gum
      for 5 min when participants reported fatigue and pain. Whereas all healthy
      subjects completed the task, 1/4 of the TMD and a majority of the WAD patients
      discontinued the task. A majority of the WAD patients also reported fatigue and
      pain. These findings suggest an association between neck injury and reduced
      functional capacity of the jaw motor system. From the results, we propose that
      routine examination of WAD patients should include jaw function and that an
      endurance test as described in this study could also be a useful tool for non
      dental professionals.

PMID- 15557404
TI  - Analysis of caries experience taking inter-observer bias and variability into
      account.
AB  - In larger oral health surveys, clinical measurements are often obtained using
      several examiners. This raises the issue of inter-observer variability in
      measurement. Often, the problem is dealt with by reporting kappa values obtained
      in a calibration exercise. In the present study, the limitations of this
      statistic are presented, and an alternative, based on a Bayesian approach, is
      proposed. When the alternative approach was applied to caries experience data
      obtained in an oral health screening survey in seven-year-old Flemish children
      (Signal Tandmobiel study), it could be ruled out that the observed geographic
      East-West gradient was due to bias induced by variability in scoring of the
      different dental examiners involved. The proposed method offers an opportunity to
      refine existing analytical approaches and is relevant to any health outcome
      study.

PMID- 15557405
TI  - Dimensions of oral-health-related quality of life.
AB  - Oral-health-related quality of life (OHRQoL) is expected to have multiple
      dimensions. It was the aim of this study to investigate the dimensional structure
      of OHRQoL measured by the Oral Health Impact Profile (German version) (OHIP-G)
      and to derive a summary score for the instrument. Subjects (N = 2050; age, 16-79
      yrs) came from a national survey. We used rotated principal-components analysis
      to derive a summary score and to explore the dimensional structure of OHIP-G. The
      first principal component explained 50% of the variance in the data. The sum of
      OHIP-G item responses was highly associated with the first principal component (r
      = 0.99). This simple but informative OHIP-G summary score may indicate that
      simple sums are also potentially useful scores for other OHRQoL instruments. Four
      dimensions (psychosocial impact, orofacial pain, oral functions, appearance) were
      found. These OHIP-G dimensions may serve as a parsimonious set of OHRQoL
      dimensions in general.

PMID- 15557406
TI  - Information and participation preferences of dental patients.
AB  - Dutch dentists have a moral and legal obligation to inform their patients and
      involve them in the decision-making process. It is unclear, though, to what
      extent patients prefer information and involvement in decision-making. Therefore,
      the aim of this study was to determine levels of preference for information and
      participation in decision-making among emergency patients (n = 96) and regular
      patients (n = 245). It was hypothesized that female gender, higher education,
      younger age, and a monitoring coping style are positively associated with higher
      preferences for information and participation. The results demonstrated that
      emergency and regular patients have high preferences for information, but that
      their preferences for actual involvement are significantly lower. Only weak
      associations were found between the antecedent variables and patients'
      preferences. It is concluded that, in the study of the etiology of patients'
      preferences for information and participation, future research should incorporate
      factors such as dental anxiety and seriousness of the dental condition.

PMID- 15557408
TI  - Hormone therapy: making decisions in the face of uncertainty.

PMID- 15557409
TI  - A systematic review and meta-analysis of studies comparing readmission rates and
      mortality rates in patients with heart failure.
AB  - BACKGROUND: Heart failure is the leading cause of hospitalization and readmission
      in many hospitals worldwide. We performed a meta-analysis to evaluate the
      effectiveness of multidisciplinary heart failure management programs on hospital
      admission rates. METHODS: We identified studies through an electronic search and
      mortality using 8 distinct methods. Eligible studies met the following criteria:
      (1) randomized controlled clinical trials of adult inpatients hospitalized for
      heart failure enrolled either at the time of discharge or within 1 week after
      discharge; (2) heart failure-specific patient education intervention coupled with
      a postdischarge follow-up assessment; and (3) unplanned readmission reported.
      Four reviewers independently assessed each study for eligibility and quality,
      achieving a weighted kappa of 0.73 for eligibility and 0.77 for quality. For each
      study we calculated the relative risk for readmissions and mortality for patients
      receiving enhanced education relative to patients receiving usual care. RESULTS:
      A total of 529 citation titles were identified, of which 8 randomized trials
      proved eligible. The pooled relative risk for hospital readmission rates using a
      random-effects model was 0.79 (95% confidence interval, 0.68-0.91; P<.001;
      heterogeneity P = .25). There was no apparent effect on mortality (relative risk,
      0.98; 95% confidence interval, 0.72-1.34; P = .90; heterogeneity P = .20). Data
      were insufficient to meaningfully pool intervention effects on quality of life or
      compliance. CONCLUSION: This systematic review suggests that specific heart
      failure-targeted interventions significantly decrease hospital readmissions but
      do not affect mortality rates.

PMID- 15557410
TI  - The burden of symptoms among community-dwelling older persons with advanced
      chronic disease.
AB  - BACKGROUND: Little is known about the frequency and range of symptoms experienced
      by community-dwelling older persons with advanced chronic disease who are not
      enrolled in hospice. The objectives of our study were to determine (1) the
      prevalence of a range of symptoms among older persons with advanced chronic
      disease and (2) whether the prevalence of symptoms is similar across diagnoses.
      METHODS: This was a cross-sectional study of the symptoms reported by 226
      community-dwelling persons 60 years or older with advanced chronic obstructive
      pulmonary disease (COPD), cancer, or congestive heart failure (CHF). Symptoms
      were assessed using the Edmonton Symptom Assessment System. RESULTS: Virtually
      all participants (86%) experienced at least 1 symptom that rated moderate or
      severe, and most (69%) experienced 2 or more symptoms. The symptoms reported by
      the greatest proportion of participants were limited activity (61%), fatigue
      (47%), and physical discomfort (38%). Participants with COPD had a higher
      unadjusted mean +/- SD number of moderate or severe symptoms (3.3 +/- 2.1) than
      did participants with cancer (2.6 +/- 1.8; P = .03) or CHF (2.0 +/- 1.7; P<.001).
      After we adjusted for sociodemographic factors, compared with participants with
      CHF, participants with cancer experienced 38% (95% confidence interval, 9%-75%)
      more moderate or severe symptoms and participants with COPD experienced 71% (95%
      confidence interval, 37%-114%) more moderate or severe symptoms. CONCLUSIONS:
      Most community-dwelling older persons with advanced COPD, cancer, or CHF
      experienced multiple moderate or severe symptoms. The clinical care of community
      dwelling older persons with advanced chronic illnesses would be enhanced by the
      identification and alleviation of the range of symptoms they experience.

PMID- 15557411
TI  - Body mass index and total and cardiovascular mortality in men with a history of
      cardiovascular disease.
AB  - BACKGROUND: Previous studies designed to identify an association between body
      mass index (BMI) (calculated as weight in kilograms divided by the square of
      height in meters) and cardiovascular or total mortality in populations with known
      atherosclerotic disease have shown conflicting results. In this study, we used
      the Physicians' Health Study enrollment cohort to examine the risk of total and
      cardiovascular mortality among men reporting a history of myocardial infarction
      or stroke, excluding those who reported a history of cancer. METHODS: Cause
      specific death was ascertained for 5010 men during a mean follow-up of 5.0 years.
      End points were classified as total deaths and deaths due to cardiovascular
      causes. Four BMI categories (<22.0, 22.0-24.9 [referent], 25.0-27.9, and > or
      =28.0) were created a priori. We used proportional hazards models to calculate
      age and multivariate-adjusted relative risks (RRs) for each BMI category for each
      end point. RESULTS: Compared with men with a BMI of 22.0 to 24.9, men with a BMI
      of 28.0 or greater had an age-adjusted RR of 1.11 (95% confidence interval [CI],
      0.91-1.36), a multivariate RR of 1.04 (95% CI, 0.84-1.28) in a model that did not
      include biological mediators of obesity, and a multivariate RR of 1.06 (95% CI,
      0.78-1.44) in a model that included these mediators. The RRs for cardiovascular
      mortality were similar, at 1.07 (95% CI, 0.85-1.35), 1.01 (95% CI, 0.79-1.29),
      and 1.01 (95% CI, 0.71-1.43), respectively. A BMI of less than 22.0 was
      associated with a small increased risk of total mortality and cardiovascular
      mortality. CONCLUSION: These findings indicate that elevated BMI may not be
      strongly associated with total or cardiovascular mortality among men with
      previously manifested coronary artery disease.

PMID- 15557412
TI  - The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects
      of antioxidant vitamins and minerals.
AB  - BACKGROUND: It has been suggested that a low dietary intake of antioxidant
      vitamins and minerals increases the incidence rate of cardiovascular disease and
      cancer. To date, however, the published results of randomized, placebo-controlled
      trials of supplements containing antioxidant nutrients have not provided clear
      evidence of a beneficial effect. We tested the efficacy of nutritional doses of
      supplementation with a combination of antioxidant vitamins and minerals in
      reducing the incidence of cancer and ischemic cardiovascular disease in the
      general population. METHODS: The Supplementation en Vitamines et Mineraux
      Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled
      primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60
      years and 5141 men aged 45-60 years) were included. All participants took a
      single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of
      vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a
      placebo. Median follow-up time was 7.5 years. RESULTS: No major differences were
      detected between the groups in total cancer incidence (267 [4.1%] for the study
      group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease
      incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98
      [1.5%]). However, a significant interaction between sex and group effects on
      cancer incidence was found (P = .004). Sex-stratified analysis showed a
      protective effect of antioxidants in men (relative risk, 0.69 [95% confidence
      interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85
      1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63
      [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for
      interaction). CONCLUSIONS: After 7.5 years, low-dose antioxidant supplementation
      lowered total cancer incidence and all-cause mortality in men but not in women.
      Supplementation may be effective in men only because of their lower baseline
      status of certain antioxidants, especially of beta carotene.

PMID- 15557413
TI  - Impact of concurrent medication use on statin adherence and refill persistence.
AB  - BACKGROUND: Effective therapy for chronic illness requires daily medication
      adherence (DMA) for prolonged periods. Overall medical regimen complexity may
      represent one barrier to successful adherence. METHODS: To assess the
      relationship between the number of concurrently prescribed medicines and
      adherence to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins), we analyzed a cohort of 5488 patients in a single health insurance
      plan who began statin therapy between July 1, 1999, and June 30, 2002. We
      assessed 2 parameters of statin adherence: (1) DMA ([total number of pills
      dispensed/total number of days between first and last prescription] x100) and (2)
      refill persistence (RP) (consecutive months of refills after initial
      prescription). RESULTS: The cohort was 61.6% male, with a mean +/- SD age of 52.7
      +/- 9.3 years. Patients were prescribed a mean +/- SD of 2.9 +/- 2 total
      medicines (range, 1-13), with a mean +/- SD statin DMA of 82.1% +/- 26.5%. By 12
      months, only 68% of patients continued filling statin prescriptions. After
      controlling for age, income level, and treatment for hypertension or ischemic
      heart disease, a greater number of concurrently prescribed medicines was
      significantly associated with better DMA (P = .005) and longer RP (P = .03).
      CONCLUSIONS: In this cohort, statin DMA was generally adequate, but RP was
      suboptimal. Patients with more concurrently prescribed medicines had higher DMA
      and better RP, even after adjusting for demographic factors and cardiovascular
      comorbidity. Physicians should not be deterred from initiating statin therapy by
      a patient's medical regimen complexity but should be alert for lack of therapy
      persistence, particularly in younger and healthier patients.

PMID- 15557414
TI  - Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without
      the hepatitis C virus: a cohort study, 1992-2001.
AB  - BACKGROUND: Because they develop slowly and infrequently, the incidence and
      relative risk of cirrhosis and hepatocellular carcinoma (HCC) in patients with
      the human immunodeficiency virus (HIV) only and in patients coinfected with the
      hepatitis C virus (HCV) are not known. METHODS: By using national Veterans Health
      Administration administrative databases, we conducted a retrospective cohort
      study. Excluding patients with preexisting liver disease, 11,678 HIV-only and
      4761 coinfected patients hospitalized between October 1, 1991, and September 30,
      2000, were included. Incidence rates and adjusted hazard ratios (HRs) for
      nonalcoholic cirrhosis and HCC after discharge were calculated through September
      30, 2001. RESULTS: The incidence rates of cirrhosis in the HIV-only and
      coinfected groups were 1.47 and 15.88 per 1000 person-years, respectively. In a
      Cox multivariate proportional hazards regression model, coinfected patients had
      an adjusted HR for cirrhosis of 9.24 compared with HIV-only patients (95%
      confidence interval, 6.92-12.33; P<.001). The incidence rates of HCC in the HIV
      only and coinfected groups were 0.20 and 1.32 per 1000 person-years,
      respectively. In a Cox multivariate proportional hazards regression model,
      coinfected patients had an adjusted HR for HCC of 5.35 compared with HIV-only
      patients (95% confidence interval, 2.34-12.20; P<.001). Among patients identified
      during the highly active antiretroviral therapy era, the HR for cirrhosis was
      19.06 (95% confidence interval, 10.14-35.85; P<.001), while the HR for HCC was
      5.07 (95% confidence interval, 1.72-14.99; P = .003). CONCLUSIONS: To our
      knowledge, this study is the largest longitudinal study to examine the incidence
      of nonalcoholic cirrhosis and HCC in HIV-only and HCV-coinfected patients.
      Hepatitis C virus coinfection dramatically promotes the development of HCC (5
      fold) and of cirrhosis (10- to 20-fold), and is especially associated with
      cirrhosis in the highly active antiretroviral therapy era. Treatment of HCV in
      HIV-infected patients, while often unsuccessful, should be considered.

PMID- 15557415
TI  - Alcohol consumption and coronary calcification in a general population.
AB  - BACKGROUND: A U- or J-shaped association exists between alcohol consumption and
      coronary heart disease. One of the proposed mechanisms for this association
      involves atherogenesis, but there are no data on the association between alcohol
      consumption and coronary atherosclerosis in asymptomatic subjects. Coronary
      calcification, a measure of coronary atherosclerosis, allows for the study of the
      association. METHODS: This cross-sectional study was performed using data from
      the population-based Rotterdam Coronary Calcification Study. Data on alcohol
      consumption were available for 1795 individuals without coronary heart disease.
      Mean +/- SD age of the participants was 71 +/- 5.7 years. Coronary calcification
      was detected on electron beam computed tomographic scans and quantified as a
      calcium score by the Agatston method. Extensive coronary calcification was
      defined as a calcium score above 400. RESULTS: In this population, 15.8% of
      individuals consumed no alcohol; 46.5% consumed 1 alcoholic drink or less per
      day; 16.9% consumed 1 to 2 drinks per day; and 20.9% consumed more than 2 drinks
      per day. A U-shaped association was found between alcohol consumption and
      coronary calcification. Compared with nondrinkers, the odds ratio of extensive
      coronary calcification was 0.60 (95% confidence interval [CI], 0.44-0.82) for
      those who consumed 1 drink or less daily; 0.51 (95% CI, 0.35-0.76) for those who
      consumed 1 to 2 drinks daily; and 0.90 (95% CI, 0.62-1.29) for those who consumed
      more than 2 drinks. The association remained after multivariate adjustment.
      CONCLUSIONS: The consumption of 2 alcoholic drinks or fewer per day was inversely
      associated with extensive coronary calcification. The risk of extensive coronary
      calcification was 50% lower in individuals who consumed 1 to 2 alcoholic drinks
      per day than in nondrinkers.

PMID- 15557416
TI  - Characterizations of long-term oxycodone/acetaminophen prescriptions in veteran
      patients.
AB  - BACKGROUND: Long-term management of chronic pain with opioids may be stable over
      time or may be complicated by problematic dose increases, drug dependencies, and
      toxic effects. To determine clinical contexts in which stability or problems may
      occur, we examined the pharmacologic and clinical correlates of long-term
      prescriptions of oxycodone/acetaminophen, a commonly prescribed short-acting
      opioid formulation. METHODS: We analyzed linked, archival outpatient pharmacy and
      clinical databases from the New England Veterans Integrated Service Network
      between January 1, 1998, and June 30, 2001. Durations, doses, and dose changes of
      oxycodone/acetaminophen prescriptions and concurrent use of long-acting opioids,
      benzodiazepines, tricyclic antidepressants, and anticonvulsants were determined.
      RESULTS: In aggregate, 2195 patients (31% with cancer diagnoses per the
      International Classification of Diseases, Ninth Revision, Clinical Modification)
      received oxycodone/acetaminophen for more than 9 months at a mean prescribed
      daily dose of 3.9 tablets per day (range, 0.5-13.0 tablets per day) with minimal
      changes in daily prescribed mean dose over time. Patients with cancer were more
      likely than other patients to receive concurrent long-acting opioids. For
      patients without cancer, a higher mean daily dose was associated with duration,
      older age, human immunodeficiency virus (HIV) and/or AIDS, and with prescribed
      benzodiazepines and long-acting opioids; concurrent benzodiazepine prescriptions
      were associated with anticonvulsant prescriptions and with psychogenic pain and
      alcohol abuse and/or dependence diagnoses. CONCLUSIONS: In veteran patients who
      received long-term oxycodone/acetaminophen prescriptions, mean daily doses were
      typically modest and stable, likely reflecting a selection of patients with
      successful, long-term management. Among patients without cancer, however,
      associations of higher oxycodone/acetaminophen doses with benzodiazepine
      prescriptions, psychogenic pain, alcohol abuse, and HIV/AIDS may portend opioid
      prescription management problems.

PMID- 15557417
TI  - Association of risk of abnormal bleeding with degree of serotonin reuptake
      inhibition by antidepressants.
AB  - BACKGROUND: Serotonin plays a role in platelet aggregation. Because
      antidepressants influence blood serotonin levels, their use may be associated
      with an increased risk of abnormal bleeding. However, previous studies were
      inconclusive regarding this association. The aim of this study was to estimate
      the risk of abnormal bleeding associated with the use of antidepressants and to
      establish the relationship between serotonin reuptake inhibition and the risk of
      bleeding. METHODS: We used data collected from 1992 through 2000 to conduct a
      nested case-control study of a cohort of more than 64 000 new antidepressant
      users. Cases were identified as all patients hospitalized for a primary diagnosis
      of abnormal bleeding, and they were matched with controls for age and sex. We
      classified exposure according to the degree (high, intermediate, or low) of
      serotonin reuptake inhibition and performed logistic regression analysis to
      calculate odds ratios. RESULTS: There were 196 cases of abnormal bleeding. The
      risk of hospitalization increased with the use of inhibitors providing
      intermediate (odds ratio, 1.9; 95% confidence interval, 1.1-3.5) and high degrees
      of serotonin reuptake inhibition (odds ratio, 2.6; 95% confidence interval, 1.4
      4.8). CONCLUSIONS: In a large population of new antidepressant users we found a
      significant association between degree of serotonin reuptake inhibition by
      antidepressants and risk of hospital admission for abnormal bleeding as the
      primary diagnosis. An increased risk of abnormal bleeding was strongly associated
      with the degree of serotonin reuptake inhibition.

PMID- 15557418
TI  - Incidence of thyroid dysfunction during interferon alfa-2b and ribavirin therapy
      in men with chronic hepatitis C: a prospective cohort study.
AB  - BACKGROUND: Thyroid dysfunction is a known complication of interferon monotherapy
      in women with hepatitis C virus (HCV) infection. The aims of this study were to
      determine the incidence and long-term outcome of thyroid dysfunction in HCV
      infected men receiving interferon and ribavirin combination therapy. METHODS: We
      prospectively studied 225 HCV-infected men with baseline levels of thyrotropin
      (TSH) within the reference range who were treated with subcutaneous interferon
      alfa-2b (3 million units 3 times per week) and oral ribavirin (1000-1200 mg/d)
      for 24 to 48 weeks. Patients underwent screening of TSH levels every 12 weeks
      during HCV therapy and at weeks 12 and 24 after completion of treatment. Patients
      with abnormal TSH levels underwent a comprehensive thyroid evaluation. RESULTS:
      Among the 225 patients, overt thyroid disease developed in 6.7% (95% confidence
      interval, 3.8%-10.8%), and subclinical thyroid disease was diagnosed in 4.0% (95%
      confidence interval, 1.8%-7.4%). In the 12 patients with overt hypothyroidism,
      antithyroglobulin antibodies were present in 11 and antithyroid peroxidase
      antibodies were present in 10, whereas thyroid-stimulating immunoglobulins were
      present in 2 of the 3 individuals with overt hyperthyroidism. Most of the
      patients with thyroid dysfunction completed HCV therapy, and thyroid disease
      resolved in 10 of the 12 patients with overt hypothyroidism, 2 of the 3 with
      overt hyperthyroidism, and all 9 with subclinical thyroid disease. CONCLUSIONS:
      Men with HCV infection treated with interferon and ribavirin should undergo
      routine screening for thyroid disease. Treatment of HCV can be safely continued
      in these patients because thyroid disease responds well to treatment and is
      reversible in most individuals.

PMID- 15557419
TI  - Health values of patients with chronic hepatitis C infection.
AB  - BACKGROUND: Patients with hepatitis C virus (HCV) infection report a reduction in
      health status, but it is not known how they value their state of health. We
      assessed health utilities directly from patients with HCV infection. METHODS: One
      hundred twenty-four patients with chronic HCV infection representing a cross
      section of disease severity were administered a disease-specific version of the
      Medical Outcomes Study 36-Item Short-Form Health Survey, the Beck Depression
      Inventory, and 3 direct health value measures, including the Rating Scale, Time
      Trade-off (TTO), and Standard Gamble (SG). Correlation among measures and factor
      analysis was performed. RESULTS: The mean modified Medical Outcomes Study 36-Item
      Short-Form Health Survey scores were lower than normative population values,
      particularly on the Physical Component Summary scale. This scale was poorly
      correlated with the Rating Scale, TTO, and SG scores among HCV-infected subjects.
      The mean +/- SE TTO score was 0.83 +/- 0.02, and the mean +/- SE SG score was
      0.79 +/- 0.02. The TTO and SG scores failed to show significant variability in
      relation to disease activity as determined by serum alanine aminotransferase
      level, histologic stage, and presence of decompensated liver disease. The Beck
      Depression Inventory was significantly inversely correlated with the TTO and SG.
      CONCLUSIONS: Although quality of life is compromised in patients with chronic HCV
      infection, patient-derived health utilities are not strongly associated with
      health status or clinical measures. Utility measures obtained from patients with
      HCV differ significantly from previous surrogate measures of health values. Such
      differences in utilities could affect decision analyses and cost-effectiveness
      analyses of treatment interventions for individuals with HCV infection.

PMID- 15557420
TI  - The spectrum of cranial neuropathy in patients with Bell's palsy.
AB  - BACKGROUND: There is controversy regarding whether, and how frequently, other
      cranial nerve deficits accompany Bell's palsy. We sought to determine
      prospectively the presence of signs indicating an associated cranial neuropathy
      in patients with Bell's palsy. METHODS: All subjects presenting to an emergency
      department with Bell's palsy over a 2-year period were evaluated. The study
      included 51 consecutive patients. One patient with Bell's palsy was not examined
      by a neurologist at the time of presentation and was excluded. The main outcome
      measure was presence of other cranial nerve deficits. RESULTS: We identified 4
      patients with additional cranial neuropathies (contralateral trigeminal [n=1],
      glossopharyngeal [n=2], and hypoglossal [n=1]). We also identified 13 patients
      with ipsilateral facial sensory loss, suggesting an ipsilateral trigeminal
      neuropathy; 3 patients with a contralateral facial palsy; and 3 patients with
      hearing impairment. CONCLUSION: This prospective study indicates that a small
      percentage (approximately 8%) of patients with otherwise typical Bell's palsy may
      harbor additional cranial neuropathies.

PMID- 15557421
TI  - Risk factors for venous thromboembolism.

PMID- 15557422
TI  - A change in definition results in an increased number of adults with prediabetes
      in the United States.

PMID- 15557423
TI  - Celiac disease must be evaluated in patients with Sjogren syndrome.

PMID- 15557425
TI  - Laminin isoforms in human extraocular muscles.
AB  - PURPOSE: To determine the laminin isoform composition of the basement membranes
      (BMs) in the human extraocular muscles (EOMs) and relate it to the fact that EOMs
      are spared in laminin alpha2-chain-deficient congenital muscular dystrophy.
      METHODS: Samples from adult human EOMs and limb muscle were processed for
      immunocytochemistry, with monoclonal antibodies against laminin chains (Ln)
      alpha1 to -5, beta1 and -2, and gamma1. Neuromuscular junctions (NMJs) were
      identified with acetylcholinesterase reaction. The capillary density was measured
      in sections stained with anti-Lnalpha5. RESULTS: The extrasynaptic BM of the EOM
      muscle fibers contained Lnalpha2, -beta1, -beta2, and -gamma1, and, in contrast
      to limb muscle, it also contained Lnalpha4 and -alpha5, to some extent. The
      distinct laminin composition of the EOMs was confirmed by the presence of
      Lutheran protein, an alpha5-chain-specific receptor not found in limb muscle. At
      the NMJs, there was increased expression of Lnalpha4 and expression of Lnalpha2, 
      alpha5, -beta1, -beta2, and -gamma1 was also maintained. The capillary density
      was very high (1050 +/- 190 capillaries/mm(2)) in the EOMs and significantly (P <
      0.05) higher in the orbital (1170 +/- 180 capillaries/mm(2)) than in the global
      (930 +/- 110 capillaries/mm(2)) layer. CONCLUSIONS: The human EOMs showed
      important differences in laminin isoform composition and capillary density when
      compared with human limb muscle and muscles of other species. The presence of
      additional laminin isoforms other than laminin-2 in the BM of the extrasynaptic
      sarcolemma could partly explain the sparing of the EOMs in Lnalpha2-deficient
      congenital muscular dystrophy.

PMID- 15557426
TI  - Expression and possible function of IL-2 and IL-15 receptors on human uveal
      melanoma cells.
AB  - PURPOSE: Interleukin-2 (IL-2) and IL-15 receptors have been detected on some
      murine neoplasms. Accordingly, the expression of these receptors on human uveal
      melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on
      melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated
      cytolysis, and sensitivity to apoptosis were assessed. METHODS: Nine human uveal
      melanoma cell lines and three cell lines from uveal melanoma metastases were
      tested by flow cytometry for the expression of human IL-2R and -15Ralpha.
      Melanoma cells were cultured, with or without recombinant human IL-2 or -15, cell
      proliferation was determined by tritiated thymidine incorporation, and IL-2 and 
      15 receptor expression was assessed by flow cytometry. The effect of these
      cytokines on NK activity was evaluated with a standard (51)Cr-release assay.
      RESULTS: All the melanoma cell lines expressed IL-2R and -15R. IL-2 induced a
      three- to eightfold upregulation of IL-2R expression in all the melanoma cell
      lines. Although IL-2 did not affect the proliferation of six of the seven uveal
      melanoma cell lines, it induced a 32% and 57% increase in the proliferation of
      both metastatic cell lines. IL-15 induced proliferation on all tested cell lines
      (4%-68%). Both IL-2 and -15 reduced melanoma cell sensitivity to NK-cell-mediated
      cytolysis and cisplatin-induced apoptosis. CONCLUSIONS: The results suggest that
      IL-2 and -15 elaborated by tumor-infiltrating lymphocytes and macrophages may
      affect the malignant behavior of human uveal melanoma by stimulating
      proliferation and reducing uveal melanoma cell susceptibility to NK-cell-mediated
      cytolysis and cisplatin-induced apoptosis.

PMID- 15557427
TI  - EpCAM expression in retinoblastoma: a novel molecular target for therapy.
AB  - PURPOSE: This study was conducted to investigate the potential of targeting
      epithelial cell adhesion molecules (EpCAMs) in the treatment of retinoblastoma.
      It was first determined whether EpCAM is expressed in retinoblastoma and then
      whether EpCAM reactivity correlates with tumor aggressiveness. METHODS: EpCAM
      reactivity was evaluated by immunohistochemistry in 43 retinoblastoma specimens
      from 43 patients, by using the monoclonal antibody GA733.2. The tumors were
      divided into two groups. There were 20 tumors with no invasion of the choroid and
      optic nerve (group A) and 23 tumors with invasion of the choroid, optic nerve,
      and orbit (group B). EpCAM reactivity was correlated with invasion and
      differentiation of the tumors. RESULTS: Among the 43 tumors, EpCAM reactivity was
      observed in 100% (43/43) tumors. EpCAM reactivity was significantly higher in the
      invasive than the noninvasive tumors (P < 0.05) and in poorly differentiated than
      in well-differentiated tumors (P < 0.005). Non-neoplastic retina also expressed
      EpCAM. CONCLUSIONS: The results confirm that EpCAM is vastly expressed in
      retinoblastoma and point to its use as a target for therapy in the future.

PMID- 15557428
TI  - Neurally selected embryonic stem cells induce tumor formation after long-term
      survival following engraftment into the subretinal space.
AB  - PURPOSE: To determine whether transplantation of embryonic stem (ES) cells into
      the subretinal space of rhodopsin-knockout mice has a tumorigenic effect.
      METHODS: Mouse ES-cell-derived neural precursor cells carrying the sequence for
      the green fluorescent protein (GFP) gene were grafted subretinally into the eyes
      of rhodopsin(-/-) mice, whereas control animals underwent sham surgery. Eyes were
      retrieved after 2, 4, and 8 weeks after cell injection or sham surgery for
      histologic analysis. RESULTS: Gross morphologic, histologic, and
      immunohistochemical analysis of eyes at 2 and 4 weeks after engraftment exhibited
      no morphologic alterations, whereas neoplasia formation was detected in 50% of
      the eyes evaluated at 8 weeks after engraftment. Because the neoplasias expressed
      differentiation characteristics of the different germ layers, they were
      considered to be teratomas. The resultant tumor formation affected almost all
      layers of the eye, including the retina, the vitreous, and the choroid.
      CONCLUSIONS: Although ES cells may provide treatment for degenerative disease in
      the future, their unlimited self-renewal and high differentiation potential poses
      the risk of tumor induction after engraftment. Thus, more care must be taken
      before using ES cell transplantation as a therapeutic option for patients with
      degenerative disease.

PMID- 15557429
TI  - Variant phenotypes of incomplete achromatopsia in two cousins with GNAT2 gene
      mutations.
AB  - PURPOSE: The present study was designed to elucidate the molecular genetic basis
      of a congenital stationary cone dysfunction characterized by congenital
      nystagmus, moderate visual impairment, and markedly disparate color vision
      deficiencies between two affected cousins. METHODS: Ophthalmic examinations with
      emphasis on color vision and electrophysiology. Molecular genetic analysis of the
      X-linked cone opsin genes, mutation screening of the CNGA3, CNGB3, and GNAT2
      genes, and heterologous splicing experiments. RESULTS: Whereas the proband was
      found to carry a homozygous frameshift mutation (Tyr95fs) in GNAT2, her cousin
      was compound heterozygous for the Tyr95fs and a new intronic mutation c.461 + 24G
      ->A. Heterologous expression in COS7 cells showed that the latter causes a
      splicing defect that results in early translation termination. Yet, this mutation
      is leaky, giving rise to small amounts of correctly spliced transcripts and offer
      an explanation for the diverging clinical findings in the cousins, one best
      described as incomplete achromatopsia and the other with oligocone trichromacy.
      CONCLUSIONS: The cases presented broaden the phenotypic spectrum of GNAT2
      mutations and underline the increasing importance of molecular genetics in the
      clinical diagnosis of atypical ophthalmic phenotypes.

PMID- 15557430
TI  - A novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like
      macular dystrophy.
AB  - PURPOSE: To conduct clinical and genetic studies in a European family with
      autosomal dominant Stargardt-like macular dystrophy (adSTGD-like MD) and to
      investigate the functional consequences of a novel ELOVL4 mutation. METHODS:
      Ophthalmic examination and mutation screening by direct sequencing of the ELOVL4
      gene was performed in two affected individuals. Wild-type and mutant ELOVL4 genes
      were expressed as enhanced green fluorescent protein (EGFP) fusion proteins in
      transient transfection in NIH-3T3 and HEK293 cells. To determine the subcellular
      localization of ELOVL4, an endoplasmic-reticulum (ER)-specific marker for pDsRed2
      ER was cotransfected with ELOVL4 constructs. Transfected cells were viewed by
      confocal microscopy. Western blot analysis was performed to assess protein
      expression using an anti-GFP antibody. RESULTS: Affected patients exhibited
      macular atrophy with surrounding flecks characteristic of adSTGD-like MD. A novel
      ELOVL4 p.Tyr270X mutation was detected in affected individuals. In cell
      transfection studies, wild-type ELOVL4 localized preferentially to the ER. In
      contrast, the mutant protein appeared to be mislocalized within transfected
      cells. CONCLUSIONS: In a European family with adSTGD-like MD, a novel ELOVL4
      mutation was found to underlie the disorder. Transfection studies indicated that,
      unlike wild-type ELOVL4, the mutant protein does not localize to the ER but
      rather appears to be sequestered elsewhere in an aggregated pattern in the
      cytoplasm. Further analysis of the function of normal and mutant ELOVL4 will
      provide insight into the mechanism of macular degeneration.

PMID- 15557431
TI  - Prevalence of refractive errors in a rural South Indian population.
AB  - PURPOSE: To report the prevalence of refractive errors in a rural south Indian
      population. METHODS: Four thousand eight hundred subjects (age, >39 years) from
      rural south India were enumerated for a population-based study. All participants
      underwent complete ophthalmic evaluation. Subjects who were phakic in the right
      eye with best corrected visual acuity of 20/40 or better were included for
      analysis. Association of refractive errors with age, sex, cataract, and diabetes
      mellitus were analyzed. RESULTS: Of the 3924 responders, 2508 were eligible. The
      unadjusted prevalence of emmetropia (spherical equivalent [SE], -0.50 to +0.50
      diopter sphere [DS]), myopia (SE < -0.50 DS), high myopia (SE < -5.00 DS), and
      hyperopia (SE > 0.50 DS) were 50.60%, 26.99%, 3.71%, and 18.70% and age and
      gender adjusted for the rural Tamil Nadu population were 46.77%, 30.97%, 4.32%,
      and 17.94%, respectively. The prevalence of emmetropia decreased significantly
      with age (P < 0.0001), and the prevalence of myopia and high myopia increased
      significantly with age (P < 0.001) and were significantly associated with nuclear
      sclerosis (P < 0.001). The prevalence of hyperopia increased until 60 years of
      age and then decreased. Hyperopia was more common among women than men (P <
      0.001) and was negatively associated with nuclear sclerosis (P < 0.001) and
      positively with diabetes mellitus (P = 0.008). Of the participants with
      astigmatism (cylindrical error greater than 0.50 DC), 9.80% had with-the-rule
      (WTR) and 77.44% against-the-rule (ATR) astigmatism. The prevalence of WTR and
      ATR astigmatism significantly decreased (P < 0.001) and increased (P = 0.006)
      with age, respectively. CONCLUSIONS: The pattern of refractive errors in this
      rural south Indian population is similar to those reported in other tropical
      regions of the world.

PMID- 15557432
TI  - Female reproductive factors and eye disease in a rural South Indian population:
      the Aravind Comprehensive Eye Survey.
AB  - PURPOSE: To determine the potential associations of female reproductive factors
      with age-related cataract, open-angle glaucoma, macular degeneration, and myopia
      in an older population of rural south India. METHODS: This was a population
      based, cross-sectional study of older adults in rural south India identified
      through a cluster sampling technique. Histories relating to female reproductive
      factors were ascertained through a questionnaire administered by trained workers.
      Detailed ocular examinations including automated perimetry were performed on all
      participants at a base hospital to arrive at a diagnosis of ocular morbidity.
      RESULTS: The study achieved a high response rate (93.0%), with examinations
      performed on 5150 of the eligible 5539 persons aged 40 years or more. Age at
      menarche was available for 2797 (98.6%) of the women and age at natural menopause
      for 1841 (98.0%) of 1878 women who were postmenopausal. The mean age at menarche
      was 14.8 +/- 1.8 years, and the mean age at menopause was 43.4 +/- 3.9 years. The
      mean duration of endogenous estrogen exposure was 28.4 +/- 4.3 years. The median
      number of pregnancies was 4 (mean, 4.3 +/- 2.6; range, 0-16). Older age at
      menarche (>or=14 years) was associated with reduced risk for age-related cataract
      and myopia, and greater risk for macular degeneration. Neither age at menopause
      nor duration of endogenous estrogen exposure was associated with any of the
      ocular diseases studied. Parity was not associated with any of the ocular
      diseases studied in a multivariate model. CONCLUSIONS: Female reproductive
      factors do not appear to influence age-related cataract, open-angle glaucoma,
      macular degeneration or myopia significantly in rural south India.

PMID- 15557433
TI  - Role of ErbB2 in Corneal Epithelial Wound Healing.
AB  - PURPOSE: Human corneal epithelial cells (HCECs) were functionally depleted of
      erbB2 to elucidate its role in epidermal growth factor (EGF) receptor (EGFR)
      activation-dependent cell migration. METHODS: The retrovirus pBabe-5R, which
      encodes an erbB2 single-chain antibody with an endoplasmic reticulum (ER)
      targeting sequence, and control pBabe-puro were used to infect THCE cells (an
      SV40-immortalized HCEC line). Several cell lines expressing 5R were selected
      along with a pBabe-puro control line. The depletion of erbB2 was verified by cell
      surface biotinylation of proteins, followed by streptavidin precipitation and
      subsequent detection of erbB2 by immunoblot analysis. Activation of erbBs was
      analyzed by immunoprecipitation using the phosphotyrosine antibody pY20, followed
      by Western blot analysis with erbB1 or erbB2 antibodies. Phosphorylation of
      extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase
      (PI3K) was analyzed by Western blot with antibodies specific to phosphorylated
      proteins. Effects of erbB2 depletion on heparin-binding EGF-like growth factor
      (HB-EGF)-induced cell migration were determined by Boyden chamber migration assay
      and by scratch wound assay. RESULTS: Wounding induced erbB2 tyrosine
      phosphorylation. Expression of 5R encoding an erbB2 single-chain antibody with an
      endoplasmic reticulum-targeting sequence depleted the cell surface expression of
      erbB2 in HCECs. Wounding resulted in a rapid increase in the phosphorylation of
      erbB1 in both 5R-expressing and control cells, whereas wound-induced erbB2
      phosphorylation in 5R-expressing cells was not detectable. Depletion of
      functional erbB2 attenuated the healing of scratch wounds in the presence of HB
      EGF and impaired both chemotactic migration stimulated by HB-EGF and haptotactic
      migration toward a fibronectin-collagen I (3:1; FNC) coating mix. Expression of
      5R affected both the intensity and the duration of wound-induced, EGFR-elicited
      ERK and PI3K activation. Inhibition of ERK and PI3K pathways in cultured porcine
      corneas impaired ex vivo epithelial wound healing. CONCLUSIONS: ErbB2 serves as a
      critical component that couples erbB receptor tyrosine kinase to the migration
      machinery of corneal epithelial cells.

PMID- 15557434
TI  - Modulation of corneal epithelial cell functions by the neutrophil-derived
      inflammatory mediator CAP37.
AB  - PURPOSE: To investigate the effect of CAP37, an inflammatory mediator in
      neutrophils, on three important events in corneal wound healing: proliferation,
      migration, and adhesion. METHODS: Immortalized human corneal epithelial cells
      (HCEC) were treated with CAP37, and its effects on migration and proliferation
      were measured using the modified Boyden chemotaxis chamber and the proliferation
      assays (CyQUANT; Molecular Probes, Eugene, OR), respectively. Effects on adhesion
      were determined by measuring upregulation of adhesion molecules belonging to the
      selectin, integrin, and immunoglobulin superfamily using RT-PCR and flow
      cytometry. RESULTS: CAP37 promoted proliferation of HCEC in a time- and dose
      dependent fashion. CAP37 was maximally chemotactic for HCEC over a range of 1.3 x
      10(-8) to 5.2 x 10(-8) M. CAP37 upregulated intercellular adhesion molecule
      (ICAM)-1, platelet endothelial cell adhesion molecule (PECAM)-1, and integrin
      molecules alpha3 (CD49c) and beta1 (CD29). Data on migration and ICAM-1 and PECAM
      1 upregulation were corroborated using primary human corneal epithelial cells.
      CONCLUSIONS: CAP37 modulated corneal epithelial cell proliferation and migration
      and upregulated adhesion molecules involved in leukocyte-epithelial and
      epithelial-extracellular matrix interactions.

PMID- 15557435
TI  - Experimental dry eye stimulates production of inflammatory cytokines and MMP-9
      and activates MAPK signaling pathways on the ocular surface.
AB  - PURPOSE: To evaluate whether experimentally induced dry eye in mice activates
      mitogen-activated protein kinase (MAPK) signaling pathways, c-Jun N-terminal
      kinases (JNK), extracellular-regulated kinases (ERK), and p38 and stimulates
      ocular surface inflammation. METHODS: 129SvEv/CD-1 mixed mice aged 6 to 8 weeks
      were treated with systemic scopolamine and exposure to an air draft for different
      lengths of time, from 4 hours to 10 days. Untreated mice were used as the
      control. The concentrations of IL-1beta and TNF-alpha in tear fluid washings and
      in corneal and conjunctival epithelia were measured by ELISA. MMP-9 in tear
      washings was evaluated by zymography, and gelatinase activity in the cornea and
      conjunctiva was determined by in situ zymography. Corneal and conjunctival
      epithelia were lysed in RIPA buffer for Western blot with MAPK antibodies, or
      they were lysed in 4 M guanidium thiocyanate solution for extraction of total
      RNA, which was used to determine gene expression by semiquantitative RT-PCR, real
      time PCR, and gene array. RESULTS: Compared with those in age-matched control
      subjects, the concentrations of IL-1beta and MMP-9 in tear fluid washings and the
      concentrations of IL-1beta and TNF-alpha and gelatinolytic activity in the
      corneal and conjunctival epithelia were significantly increased in mice receiving
      treatments to induce dry eye after 5 or 10 days. The expression of IL-1beta, TNF
      alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also
      stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2,
      ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly
      increased as early as 4 hours after treatment, and they remained elevated up to 5
      days. CONCLUSIONS: Experimental dry eye stimulates expression and production of
      IL-1beta, TNF-alpha, and MMP-9 and activates MAPK signaling pathways on the
      ocular surface. MAPKs are known to stimulate the production of inflammatory
      cytokines and MMPs, and they could play an important role in the induction of
      these factors that have been implicated in the pathogenesis of dry eye disease.

PMID- 15557436
TI  - Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in
      human corneal epithelial cells.
AB  - PURPOSE: To investigate whether exposure of human corneal epithelial cells to
      hyperosmotic stress activates the c-Jun NH(2)-terminal kinase (JNK) stress
      activated protein kinase (SAPK) pathway, and stimulates production of the matrix
      metalloproteinases (MMPs): gelatinase (MMP-9), collagenases (MMP-1 and -13), and
      stromelysin (MMP-3). METHODS: Primary human corneal epithelial cells cultured in
      normal osmolar medium (312 mOsM) were exposed to media with higher osmolarity
      (350-500 mOsM) achieved by adding NaCl, with or without SB202190, an inhibitor of
      the JNK pathway; dexamethasone; or doxycycline for different lengths of time. The
      conditioned media were collected after 24 hours of exposure for zymography and
      ELISA. Total RNA was extracted from cultures treated for 6 hours and subjected to
      semiquantitative RT-PCR. Cells treated for 5 to 60 minutes were lysed in RIPA
      buffer and subjected to Western blot with phospho (p)-specific antibodies against
      p-JNK and p-c-Jun. JNK1 activation was also detected with an immunoassay system.
      RESULTS: The concentrations of MMP-9, -1, and -3 proteins in 24-hour conditioned
      media of corneal epithelial cells progressively increased as the media's
      osmolarity was increased from 312 to 500 mOsM by the addition of NaCl. The
      concentration of MMP-13 progressively increased to a peak at 450 mOsM. Active p
      JNK-1, p-JNK-2, and p-c-Jun were detected by Western blot as early as 5 minutes
      and peaked at 60 minutes in cells exposed to hyperosmolar media. The levels of p
      JNK-1, p-JNK-2, and p-c-Jun correlated positively with the osmolarity of the
      culture media. The p-JNK inhibitor SB202190 and doxycycline markedly inhibited
      the stimulation of p-JNK-1, p-JNK-2, and p-c-Jun, as well as MMP-9, -1, -13, and 
      3 at both the mRNA and protein levels in the cells exposed to hyperosmolar media.
      CONCLUSIONS: Expression and production of MMP-9, -1, -13, and -3 by human corneal
      epithelial cells correlated positively with increasing media osmolarity. This
      increase was mediated at least in part through activation of the JNK SAPK
      pathway. Doxycycline, an agent used to treat MMP-mediated ocular surface disease,
      inhibited the hyperosmolarity-induced MMP production and JNK activation. The
      relevance of these findings to stimulated production of MMPs by the elevated tear
      osmolarity in dry eye remains to be determined.

PMID- 15557437
TI  - Corneal aberrations before and after small-incision cataract surgery.
AB  - PURPOSE: To study the effect of small-incision cataract surgery on the optical
      aberrations of the cornea. METHODS: Corneal topography was measured before and
      after cataract surgery on 70 eyes of 70 patients. Monofocal foldable IOLs were
      implanted after phacoemulsification through a clear-cornea, 3.5-mm incision
      without suture. Corneal aberrations, up to the fifth order and 6-mm pupil, were
      calculated by ray-tracing from the corneal topography. Pre- and postoperative
      aberrations were compared in each patient and the optical changes induced by
      surgery investigated. RESULTS: The root mean square of the wave aberration
      slightly increased on average after surgery (pre, 0.65 +/- 0.46 microm; post,
      0.85 +/- 0.63 microm). Most aberration terms were similar, averaged across the 70
      patients, before and after surgery (spherical aberration: pre, 0.32 +/- 0.12
      microm, and post, 0.34 +/- 0.19 microm; astigmatism: pre, 0.9 +/- 0.8 D, and
      post, 1.1 +/- 1.0 D; coma: pre, 0.27 +/- 0.18 microm, and post, 0.32 +/- 0.33
      microm). However, in each patient, there were changes after surgery in the
      magnitude (either increasing or decreasing) and/or orientation of aberrations.
      The mean induced astigmatism was -1.0 +/- 0.9 D at the orientation of the
      surgical meridian. Induced trefoil also showed a predominant pattern at this
      direction. Patients with nasal incisions experienced larger changes. CONCLUSIONS:
      Small-incision surgery does not systematically degrade the optical quality of the
      anterior corneal surface. However, it introduces changes in some aberrations,
      especially in nonrotationally symmetric terms such as astigmatism, coma, and
      trefoil. The incision site plays a main role in the corneal changes after
      surgery.

PMID- 15557438
TI  - Induction of epithelial progenitors in vitro from mouse embryonic stem cells and
      application for reconstruction of damaged cornea in mice.
AB  - PURPOSE: Severe ocular surface diseases and injuries cause loss of the corneal
      limbal epithelium, leading to re-epithelialization by bulbar conjunctival cells,
      resulting in vascularization of the cornea, conjunctival scarring, and loss of
      visual acuity. In this study, the optimal culture condition for induction of
      differentiation of epithelial progenitor cells from embryonic stem (ES) cells was
      determined for use in transplantation to damaged cornea in mice. METHODS: Mouse
      ES cells were cultured on Petri dishes coated with several extracellular matrix
      proteins, and the markers for epithelial cells were analyzed with RT-PCR and
      Western blot analysis. The optimal condition for induction of epithelial
      progenitor cells was determined, and the progenitors were transplanted onto mouse
      eyes with corneal epithelia that had been damaged by exposure to n-heptanol.
      RESULTS: Epithelial progenitors were successfully induced by culturing mouse ES
      cells on type IV collagen for 8 days. These progenitors expressed keratin (K)12,
      which is specific to corneal epithelial cells, and cell surface CD44 and E
      cadherin, both of which are essential in corneal epithelial wound healing.
      Complete re-epithelialization of the corneal surface occurred within 24 hours
      after transplantation. The resultant corneal epithelial cells expressed markers
      of the grafted cells, and no teratomata were observed during the follow-up
      period. CONCLUSIONS: Epithelial progenitors were successfully induced in vitro
      from ES cells and were applicable as grafts for treating corneal epithelial
      injury. ES cells may become an unlimited donor source of corneal epithelial cells
      for corneal transplantation and may restore useful vision in patients with a
      deficiency of limbal epithelial cells. This is an important first trial toward
      assessing the use of ES cells to reconstruct corneal epithelial cells.

PMID- 15557439
TI  - Developmentally regulated expression of KLF6 in the mouse cornea and lens.
AB  - PURPOSE: To examine the expression of transcription factor Kruppel-like factor-6
      (KLF6) in the cornea and lens of mouse eyes throughout developmental stages.
      METHODS: C57BL/6 mice were set up for timed mating. Embryos on embryonic day
      (E)10.5, E12.5, E15.5, and E18.5 and eyes from mice on postnatal day (P)0, P7,
      P11, P15, P30, and P60 were collected for immunofluorescence staining. Transcript
      of KLF6 was detected by in situ hybridization with digoxigenin-labeled RNA
      probes. Relative quantitative reverse transcription (RT)-PCR was performed to
      measure the KLF6 transcript level in eyes enucleated at embryonic stages, and the
      corneas and lenses isolated at postnatal stages. RESULTS: Staining for the KLF6
      protein was observed at E10.5 in the lens pit and at E12.5 in the ectoderm, the
      mesenchyme, and the lens epithelium. Nuclear staining for KLF6 protein was
      evident at E15.5 in the corneal epithelium and the stroma. The staining was
      abundant between E18.5 and P60. In the lens epithelium, nuclear staining was
      detected at P0, P7, and P11. The staining intensity declined subsequently. The
      KLF6 transcript was found in the lens pit at E10.5 and in the ectoderm and
      mesenchyme at E12.5. The KLF6 mRNA level in corneal layers remained relatively
      constant until P60. In the lens epithelium, it was high during embryonic stages
      but decreased with development. CONCLUSIONS: KLF6 is expressed in both the cornea
      and the lens in mouse eyes. Its expression in the lens is temporally regulated,
      suggesting that it has a central role in lens development.

PMID- 15557440
TI  - Optotype and grating visual acuity in patients with ocular and cerebral visual
      impairment.
AB  - PURPOSE: To investigate the discrepancy between grating and optotype visual
      acuity in children with visual impairment due to brain and/or ocular
      abnormalities. METHODS: Better eye acuity at 114 cm was studied in 81 patients
      (ages, 5-24 years) attending special schools for the visually handicapped.
      Fourteen patients had a brain abnormality, 48 had an ocular disorder, and 19 had
      both. Three acuity tasks were administered: detecting gratings in one of two
      positions, discriminating the orientation of single gratings, and discriminating
      the orientation of uncrowded Landolt-C optotypes. The three paradigms were
      similar in stimulus contrast, luminance, presentation mode, and psychophysical
      procedure. RESULTS: Overall, grating acuity was better than optotype acuity, and
      the disparity increased with poorer optotype acuity. The largest discrepancies
      occurred in patients with brain abnormality, but disparities were also large in
      patients with optic nerve disorder. In patients with ocular and brain
      abnormality, grating acuities were only mildly better and not different from
      patients with only ocular abnormality. Grating orientation and grating detection
      tasks yielded similar thresholds, except in patients with cerebral visual
      impairment and with optic nerve disorder, whose grating detection acuity was
      better than grating orientation acuity. CONCLUSIONS: Grating-to-optotype acuity
      superiority is typically large in visual disorders involving the brain. The
      closely matched test paradigms point to stimulus characteristics as the
      explanation. However, because the discrepancy decreased with grating orientation
      acuity instead of grating detection acuity, the complexity of the response
      required also plays a role.

PMID- 15557441
TI  - Tissue adhesives for a sutureless fadenoperation: an experimental study in a
      rabbit model.
AB  - PURPOSE: To use tissue adhesives for a sutureless Fadenoperation to eliminate
      perioperative risks related to the sutures. METHODS: In an in vivo procedure, 120
      superior recti muscles in New Zealand White rabbits were subjected to the
      posterior fixation procedure, at a distance of 6 mm from the insertion point of
      the muscle. They were divided into four groups of 30 muscles, according to the
      material used to perform a myopexy: group 1 (control): nonabsorbable 5-0
      polyester sutures; group 2: n-butyl-2-cyanoacrylate adhesive; group 3: fibrin
      glue; group 4: gelatin-resorcin-formaldehyde-glutaraldehyde (GRFG) adhesive. The
      animals were examined at 1, 7, 14, and 21 days after surgery. Afterward, they
      were killed, and their eyes were enucleated to measure the distance between the
      myopexy and the anatomic insertion point and to assure the strength of the bond
      with a dynamometer. Finally, a histologic examination was performed. RESULTS:
      Almost all eyes were clear after the third week, although group 4 presented the
      most intense inflammatory reaction. In histologic examination, groups 1 and 2
      showed a chronic inflammatory reaction of the foreign-body type, with similar
      intensity. Fibrin glue induced minimal inflammation, but GRFG adhesive produced a
      pronounced reaction. Concerning the distance of the myopexy, groups 1 and 2
      presented measures close to the expected distance of 6 mm, whereas groups 3 and 4
      showed a greater variability. All groups performed well in the strength test,
      with no statistically significant differences among them. CONCLUSIONS: n-Butyl-2
      cyanoacrylate adhesive performed best in the sutureless Fadenoperation,
      characterized by precision in the expected distance of myopexy, sufficient
      resistance to separation, and acceptable inflammatory reaction.

PMID- 15557442
TI  - Prediction of visual field progression in glaucoma.
AB  - PURPOSE: To determine the probability of future glaucomatous visual field (VF)
      progression with clinical and perimetric data. METHODS: One hundred sixty-one
      eyes of patients (161) enrolled in the Advanced Glaucoma Intervention Study
      (AGIS) with >or=8 years of follow-up and a baseline VF score <or=16 were
      selected. VF progression at 8 years was determined with point-wise linear
      regression (PLR) analysis, using a two-omitting algorithm. The course of VF
      series over the first 4 years of follow-up was quantified by an index, the sum of
      slopes, which is the sum of all slopes of VF thresholds with P < 0.05 when PLR
      was performed on the 4-year data. The following parameters were included in a
      logistic regression model to predict 8-year outcomes from the first 4 years of
      follow-up: intervention sequence, age, AGIS VF score, mean IOP, IOP fluctuation,
      and sum of slopes. RESULTS: Sixty-four (40%) eyes progressed after 8 years as
      determined by PLR analysis. Two parameters were predictive of subsequent VF
      progression, as identified at 8 years (predictive power: 76%): more negative sum
      of slopes (i.e., faster or more extensive deterioration; P < 0.001) and older age
      at 4 years (P = 0.049). When sum of slopes alone was used to predict outcomes at
      8 years, the predictive power was the same. CONCLUSIONS: The VF sum of slopes can
      be used to estimate the probability of subsequent VF worsening with reasonable,
      clinically useful accuracy. This probability may be combined with other clinical
      information for more effective clinical predictions and treatment decisions.

PMID- 15557443
TI  - Regional optic nerve damage in experimental mouse glaucoma.
AB  - PURPOSE: To assess the relationship between regional variation of axon loss and
      optic nerve head anatomy in laser-induced experimental glaucoma in the mouse.
      METHODS: Experimental glaucoma was induced unilaterally in eight NIH Swiss black
      mice. Intraocular pressure (IOP) was measured for 12 weeks, and the mice were
      killed. The eyes were enucleated, and both optic nerves were dissected and
      processed conventionally for electron microscopy. Low- and high-magnification
      images of the optic nerve cross sections 300 microm posterior to the globe were
      collected systematically and masked before analysis. For each nerve, cross
      sectional area was measured in low-magnification micrographs. Axon number and
      density were determined in the high-magnification micrographs. Loss of axonal
      density was compared between the superior and inferior and nasal and temporal
      areas of the optic nerve cross section. Additional cross-section micrographs were
      collected at 10- or 20-microm intervals throughout the optic nerve head. RESULTS:
      In the treated (glaucoma) eyes, mean IOP was 44% higher than that in the control
      eyes. The optic nerve cross-sectional area, mean axonal density, and total axonal
      number were significantly less than those in the control eyes (P < 0.01 for
      each). Axon loss in the superior optic nerve was greater than in the inferior
      optic nerve in each glaucomatous eye (P = 0.012). The ratio of axonal density in
      the superior and inferior optic nerve (superior-to-inferior [S/I] ratio) in all
      treated eyes was <1.0 and significantly lower than that in the control eyes (P =
      0.012). The central retinal vessels occupied approximately 20% of the central
      optic nerve head cross-sectional area, gradually shifted position ventrally as
      they progressed toward the scleral foramen (the mouse does not have a lamina
      cribrosa), and exited the inferior retrobulbar optic nerve adjacent to the
      posterior of the globe. CONCLUSIONS: Ocular hypertension in the mouse eye
      sufficient to cause optic nerve damage induces preferential loss of superior
      optic nerve axons. Optic nerve axon loss appeared less among the axons that were
      near the major optic nerve blood vessels at the scleral foramen. Topographic
      differences in optic nerve axon loss should be considered when evaluating optic
      nerve damage in experimental laser-induced glaucoma in the mouse.

PMID- 15557444
TI  - Variants in optineurin gene and their association with tumor necrosis factor
      alpha polymorphisms in Japanese patients with glaucoma.
AB  - PURPOSE: To investigate sequence variations in the optineurin (OPTN) gene and
      their association with TNF-alpha polymorphisms in Japanese patients with
      glaucoma. METHODS: The OPTN gene was analyzed in blood samples from 629 Japanese
      subjects. There were 194 patients with primary open-angle glaucoma (POAG), 217
      with normal-tension glaucoma (NTG), and 218 with no eye disease (control
      subjects). The gene was screened for mutations by denaturing high-performance
      liquid chromatography. Genotyping of three polymorphisms of -308G-->A, -857C-->T,
      and -863C-->A in the TNF-alpha promoter region was performed. The associations
      between the genotypes and age, intraocular pressure (IOP), and visual field
      defects at the time of diagnosis were examined. RESULTS: A possible glaucoma
      causing mutation, His26Asp, was identified in 1 of the 411 Japanese patients with
      glaucoma. A c.412G-->A (Thr34Thr) polymorphism in the OPTN gene was significantly
      associated with POAG (genotype frequency, P = 0.011; allele frequency, P =
      0.003). The frequency of TNF-alpha/-857T and optineurin/412A carriers was
      significantly higher (P = 0.006) in patients with POAG than in control subjects.
      Among the patients with POAG who were carriers of TNF-alpha/-857T, the
      optineurin/412A carriers had significantly worse (P = 0.020) visual field scores
      than the non-optineurin/412A ones. The frequency of TNF-alpha/-863A and
      optineurin/603A (or Lys98) carriers was significantly higher in patients with
      POAG (P = 0.008) or NTG (P = 0.027) than in control subjects. Among the patients
      with POAG who were carriers of TNF-alpha/-863A, the ones with optineurin/603A (or
      Lys98) had significantly worse (P = 0.026) visual field scores than did those
      with non-optineurin/603A (or Lys98). CONCLUSIONS: These findings demonstrated
      that the OPTN gene is associated with POAG rather than NTG in the Japanese.
      Statistical analysis showed a possible interaction between polymorphisms in the
      OPTN and the TNF-alpha genes that would increase the risk for glaucoma.

PMID- 15557445
TI  - Prostaglandin FP agonists alter metalloproteinase gene expression in sclera.
AB  - PURPOSE: The present study was undertaken to determine whether exposure of the
      sclera to prostaglandin (PG)F(2alpha) or to the PGF(2alpha) analogue latanoprost
      acid alters mRNA for matrix metalloproteinases. METHOD: Fifteen human eye bank
      eyes were studied. Circular pieces of sclera were either immediately preserved in
      a stabilization reagent or cultured in low-serum DMEM/F-12 medium. The cultures
      were treated for 24 hours with medium supplemented with PGF(2a), latanoprost
      acid, or vehicle. Total RNA was then isolated, and the expression of mRNA for
      matrix metalloproteinase (MMP)-1, -2, -3, -8, -9, -10, and -12 were determined by
      real-time PCR. All results were normalized according to the GAPDH mRNA in each
      sample. Altered mRNA expression after PG treatments also was evaluated with
      microarrays containing 19 MMP genes and 4 tissue inhibitor of matrix
      metalloproteinase (TIMP) genes. RESULTS: Real-time PCR results showed that 24
      hours of exposure to 100 nM PGF(2alpha) significantly increased mRNA for MMP-1
      and -9 (P < 0.06 Wilcoxon test) and that exposure to 100 nM latanoprost acid
      significantly increased mRNA for MMP-9 (P < 0.06 Wilcoxon test). Array analysis
      demonstrated increases of MMP-3 and -10 mRNA after exposure to 100 nM latanoprost
      and further increases after exposure to 200 nM latanoprost. The array results
      also showed that latanoprost induced dose-dependent increases in the expression
      of TIMP-1, -2, and -3 mRNA in the scleral cultures. CONCLUSIONS: PGF(2alpha) and
      latanoprost acid induce coordinated alterations of MMP gene transcription in
      scleral organ cultures. These results indicate that PGs can directly trigger MMP
      gene transcription changes within the sclera. These changes support a role for
      increased MMPs in the enhancement of uveoscleral outflow that occurs after
      topical treatment with latanoprost.

PMID- 15557446
TI  - Finite element modeling of optic nerve head biomechanics.
AB  - PURPOSE: Biomechanical factors have been implicated in the development of
      glaucomatous optic neuropathy, particularly at the level of the lamina cribrosa.
      The goal of this study was to characterize the biomechanics of the optic nerve
      head using computer modeling techniques. METHODS: Several models of the optic
      nerve head tissues (pre- and postlaminar neural tissue, lamina cribrosa, central
      retinal vessel, sclera, and pia mater) were constructed. Stresses, deformations,
      and strains were computed using finite element modeling for a range of normal and
      elevated intraocular pressures. Computed retinal surface deformations were
      compared with measured deformation patterns in enucleated human eyes. A
      sensitivity analysis was performed in which tissue properties and selected
      geometric features were varied. RESULTS: Acute IOP-induced deformation of the
      vitreoretinal interface was highly dependent on optic cup shape but showed a
      characteristic "W-shaped" profile that did not match the deformation of the
      anterior surface of the lamina cribrosa. The central retinal vasculature had
      surprisingly little effect on optic nerve head biomechanics. At an IOP of 50 mm
      Hg, strains (fractional elongation) in the lamina cribrosa averaged 4% to 5.5%,
      dependent on model geometry, with maximum strains up to 7.7%. Strains in the
      lamina cribrosa were more dependent on scleral stiffness, scleral thickness, and
      scleral canal diameter than on lamina cribrosa stiffness and optic cup shape.
      CONCLUSIONS: Computed levels of strain in the lamina cribrosa are biologically
      significant and capable of contributing to the development of glaucomatous optic
      neuropathy, even without considering the probable accentuating effect of the
      lamina cribrosa's microarchitecture. Depending on optic cup shape, IOP-induced
      deformation of the vitreoretinal interface may not match lamina cribrosa
      deformation. This finding implies that scanning laser tomography has limited
      ability to estimate lamina cribrosa deformation when imaging the anterior
      topography of the optic nerve head. Biomechanical effects in the lamina cribrosa
      depend strongly on scleral properties.

PMID- 15557447
TI  - Three-dimensional reconstruction of normal and early glaucoma monkey optic nerve
      head connective tissues.
AB  - PURPOSE: To introduce high-resolution, digital three-dimensional (3-D)
      reconstruction of the connective tissues of the optic nerve head (ONH). METHODS:
      Trephinated ONH and peripapillary sclera from both eyes of three monkeys with
      early glaucoma (EG; one eye normal, one eye given laser-induced EG) were embedded
      in paraffin and serial sectioned at 3-mum thickness from the vitreous surface
      through the orbital optic nerve, with the embedded tissue block face stained and
      imaged after each cut. Each image was aligned, and then the scleral canal wall,
      sclera, border tissue of Elschnig, Bruch's membrane, lamina cribrosa, optic nerve
      septa, pial sheath, and vasculature were delineated as unique objects. Delineated
      images were stacked, color mapped, and volume rendered and then serial sagittal
      and transverse digital sections of the resultant voxel geometries were viewed and
      measured. RESULTS: Substantial differences in the 3-D architecture of the
      peripapillary sclera, scleral canal wall, and lamina cribrosa were present among
      the three normal eyes. All three EG eyes displayed permanent posterior
      deformation of the central lamina cribrosa, as well as expansion of the anterior
      and posterior neural canal openings in comparison with their respective
      contralateral normal control eyes. Peripherally, whereas laminar deformation was
      greatest inferiorly or superiorly in all three EG eyes, statistically significant
      deformation was present in all four quadrants of all three eyes. CONCLUSIONS:
      High-resolution, digital 3-D reconstructions of the load-bearing connective
      tissues of the monkey ONH confirm that the ONH connective tissues are profoundly
      altered at the onset of detectable ONH surface change in experimental glaucoma.

PMID- 15557448
TI  - Cl- influx into rat cortical lens fiber cells is mediated by a Cl- conductance
      that is not ClC-2 or -3.
AB  - PURPOSE: Exposure of organ-cultured lenses to Cl(-) channel blockers under
      isotonic conditions induces a localized cortical zone of extracellular space
      dilations. The purpose of this study was to investigate whether elongated lens
      fiber cells from this zone contain an anion conductance that mediates Cl(-)
      influx and whether two chloride channel isoforms known to be expressed in the
      lens (ClC-2 and -3) are responsible. METHODS: Fiber cells were isolated by
      enzymatic dissociation in the presence of Gd(3+) and Co(2+) and their electrical
      properties analyzed by whole-cell patch clamping. Cells from the zone of
      extracellular space dilations were selected for analysis on the basis of cell
      length. RT-PCR and immunocytochemistry were used to determine whether ClC-2 or -3
      channel isoforms are expressed in fiber cells located in the zone of
      extracellular space dilations. RESULTS: Cells from the zone of extracellular
      space dilations were typically >120 microm in length and exhibited an outwardly
      rectifying Cl(-) conductance that was blocked by DIDS (4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid) and displayed an anion selectivity
      sequence of I(-) > Cl(-) >> gluconate. ClC-2 and -3 were found to be expressed at
      the transcript and protein level in lens fiber cells, but subsequent
      immunocytochemical studies indicated that expressed proteins did not colocalize
      with cell membranes in the zone of extracellular space dilations, being
      predominately cytoplasmic in nature. CONCLUSIONS: Taken together, the data
      indicate that extracellular space dilations are due to the inhibition of a Cl(-)
      channel(s) that normally mediates Cl(-) influx into cortical lens fiber cells
      under isotonic conditions. The molecular identity of this channel remains to be
      determined.

PMID- 15557449
TI  - Identification and spatiotemporal characterization of spontaneous Ca2+ sparks and
      global Ca2+ oscillations in retinal arteriolar smooth muscle cells.
AB  - PURPOSE: To identify spontaneous Ca(2+) sparks and global Ca(2+) oscillations in
      microvascular smooth muscle (MVSM) cells within intact retinal arterioles and to
      characterize their spatiotemporal properties and physiological functions.
      METHODS: Retinal arterioles were mechanically dispersed from freshly isolated rat
      retinas and loaded with Fluo-4, a Ca(2+)-sensitive dye. Changes in [Ca(2+)](i)
      were imaged in MVSM cells in situ by confocal scanning laser microscopy in x-y
      mode or line-scan mode. RESULTS: The x-y scans revealed discretely localized,
      spontaneous Ca(2+) events resembling Ca(2+) sparks and more global and prolonged
      Ca(2+) transients, which sometimes led to cell contraction. In line scans, Ca(2+)
      sparks were similar to those previously described in other types of smooth
      muscle, with an amplitude (DeltaF/F(0)) of 0.81 +/- 0.04 (mean +/- SE), full
      duration at half maximum (FDHM) of 23.62 +/- 1.15 ms, full width at half maximum
      (FWHM) of 1.25 +/- 0.05 mum, and frequency of 0.56 +/- 0.06 seconds(-1).
      Approximately 35% of sparks had a prolonged tail (>80 ms), similar to the
      Ca(2+)"embers" described in skeletal muscle. Sparks often summated to generate
      global and prolonged Ca(2+) elevations on which Ca(2+) sparks were superimposed.
      These sparks occurred more frequently (2.86 +/- 025 seconds(-1)) and spread
      farther across the cell (FWHM = 1.67 +/- 0.08 microm), but were smaller
      (DeltaF/F(0) = 0.69 +/- 0.04). CONCLUSIONS: Retinal arterioles generate Ca(2+)
      sparks with characteristics that vary during different phases of the spontaneous
      Ca(2+)-signaling cycle. Sparks summate to produce sustained Ca(2+) transients
      associated with contraction and thus may play an important excitatory role in
      initiating vessel constriction. This deserves further study, not least because
      Ca(2+) sparks appear to inhibit contraction in many other smooth muscle cells.

PMID- 15557450
TI  - Intraocular pressure in zebrafish: comparison of inbred strains and
      identification of a reduced melanin mutant with raised IOP.
AB  - PURPOSE: The goal was to establish an accurate method for measuring intraocular
      pressure (IOP) in living adult zebrafish and to determine the average IOPs of
      genetically different strains and mutants. The overall purpose was to develop the
      zebrafish system for studies of IOP and glaucoma. Elevated IOP and anterior
      segment dysgenesis are two known risk factors for glaucoma. Because albino
      mammals have increased IOP and are prone to anterior segment anomalies, the study
      was focused on a reduced melanin zebrafish mutant, brass. METHODS: Servo-null
      electrophysiology was used to measure IOP in anesthetized adult zebrafish. A
      pulled-glass microelectrode was used to penetrate the cornea into the anterior
      chamber, and pressure transduction was recorded. IOP, histology, and visual
      behavioral assays were used to assess the brass mutant. RESULTS: Significant
      differences in IOP were detected between genetically distinct zebrafish strains.
      IOP averages were highest in the long fin (LF) strain (20.5 +/- 1.2 mm Hg) and
      lowest in the Oregon AB (AB) strain (10.8 +/- 0.3 mm Hg). In brass mutants, which
      show a reduced melanin phenotype, IOPs were elevated and mild iris hypoplasia was
      noted. No defects were observed within the retina or in visual function.
      CONCLUSIONS: In the present study, an accurate method was developed for measuring
      IOP in adult zebrafish. Both the ability to measure IOP in the genetically
      powerful zebrafish model and the conservation of elevated IOP and anterior
      segment anomalies between albino mammals and hypopigmented fish are important.
      They strongly support the use of zebrafish for studying the complex genetics of
      elevated IOP and glaucoma.

PMID- 15557451
TI  - Aquaporin-dependent water permeation at the mouse ocular surface: in vivo
      microfluorimetric measurements in cornea and conjunctiva.
AB  - PURPOSE: Fluorescence methods were developed to quantify membrane and tissue
      water permeabilities at the ocular surface and to compare water transport in wild
      type mice versus transgenic mice lacking each of the water channels, aquaporin
      (AQP)-1, -3, and -5, normally expressed in cornea or conjunctiva. METHODS:
      Membrane water permeabilities (P(f)(mem)) of calcein-stained surface epithelial
      cells were measured from the kinetics of fluorescence quenching in response to
      rapid (<0.2 seconds) changes in extraocular fluid osmolarity. Tissue water
      permeabilities (P(f)(tiss)) across intact cornea and conjunctiva--the relevant
      parameters describing water movement into the hyperosmolar tear film in vivo-
      were determined by a dye-dilution method from the fluorescence of Texas red
      dextran in an anisosmolar solution in a microchamber at the ocular surface.
      RESULTS: Osmotic equilibration occurred with an exponential time constant (tau)
      of 1.3 +/- 0.2 seconds (P(f)(mem) = 0.045 cm/s) in calcein-loaded corneal
      epithelial cells of wild-type mice, slowing 2.1 +/- 0.4-fold in AQP5-deficient
      mice; tau was 2.4 +/- 0.1 seconds in conjunctiva (P(f)(mem) = 0.025 cm/s),
      slowing 3.6 +/- 0.7-fold in AQP3-deficient mice. In dye-dilution experiments,
      P(f)(tiss) of cornea was 0.0017 cm/s and decreased by greater than fivefold in
      AQP5-deficient mice. P(f)(tiss) in AQP5-null mice was restored to 0.0015 cm/s
      after removal of the epithelium. P(f)(tiss) of conjunctiva was 0.0011 cm/s and
      was not sensitive to AQP3 deletion. CONCLUSIONS: These results define for the
      first time the water-transporting properties of the two principal ocular surface
      barriers in vivo. The permeability data were incorporated into a mathematical
      model of tear film osmolarity, providing insights into the pathophysiology of dry
      eye disorders.

PMID- 15557452
TI  - A homozygosity-based search for mutations in patients with autosomal recessive
      retinitis pigmentosa, using microsatellite markers.
AB  - PURPOSE: To identify possible mutations in known candidate genes in patients with
      autosomal recessive (ar) and simplex retinitis pigmentosa (RP), by using an
      established strategy of flexible, multiplexed, microsatellite-based homozygosity
      mapping. METHODS: A total of 78 microsatellite markers corresponding to 16 genes
      known to be responsible for arRP were selected and used in 18 multiplex
      amplifications, followed by genotyping. Twelve consanguineous probands and 47
      nonconsanguineous probands (59 patients with arRP or simplex RP) agreed to the
      screening. RESULTS: Of the 59 probands examined, 24 had a mean of 1.4 genes
      showing homozygosity for all markers within the corresponding gene region.
      Subsequent direct sequencing revealed three homozygous mutations. Two of them
      were novel mutations in the genes TULP1 (c.1145T-->C, F382S) and CNGB1 (c.3444 +
      1G-->A). The other was a mutation in RPE65 (c.1543C-->T, R515W), which is known
      to cause Leber's congenital amaurosis. The clinical features of each patient,
      together with the cosegregation analysis, strongly support the pathogenicity of
      these mutations. CONCLUSIONS: This systematic approach facilitated the
      identification of genes that cause arRP, and the results provide a widened
      spectrum of the mutation severity associated with a broader range of phenotypic
      manifestations of arRP.

PMID- 15557453
TI  - Integration between abutting retinas: role of glial structures and associated
      molecules at the interface.
AB  - PURPOSE: Integration between subretinal grafts and the host retina is limited in
      part by the presence of a barrier at the graft-host interface. This study was
      conducted to identify factors that may contribute to this barrier, by examining
      the distribution of glial structures and associated molecules in different setups
      of overlapping retinal pieces. METHODS: Neuroretinal tissue derived from mice
      that express green fluorescent protein (GFP) was fragmented and transplanted into
      the subretinal space of adult rd1 mice. In an in vitro system, two retinal
      pieces, derived from GFP and rd1 mice, respectively, were placed overlapping each
      other and forming either laminar-laminar pairs or fragment-laminar pairs. The
      glia-associated markers analyzed included glial fibrillary acidic protein (GFAP),
      cellular retinaldehyde-binding protein (CRALBP), and two molecules known to
      inhibit neurite outgrowth: CD44 and neurocan. Bridging fibers and migrated cells
      were visualized with GFP fluorescence and retinal cell markers. RESULTS: A thick
      CRALBP-immunolabeled band was observed in the interface in cultured laminar
      laminar pairs, whereas a thinner band was seen in cultured fragment-laminar pairs
      and in transplants. Accumulation of CD44 and neurocan was also observed in the
      interface between abutting retinal pieces in all setups. GFP(+) bridging fibers
      and GFP(+) cells (some of which coexpressed neuronal markers) were observed
      within the abutting rd1 retina in some areas. However, such integration occurred
      exclusively where CRALBP, CD44, and neurocan immunolabeling appeared disrupted in
      the interface, but coincided with high GFAP expression within the rd1 retina.
      CONCLUSIONS: The results demonstrate that, on the one hand, an accumulation of
      glial-associated inhibitory molecules in the interface correlates with limited
      integration between overlapping retinal pieces. On the other hand, glial
      reactivity within the rd1 retina does not appear to be incompatible with
      integration.

PMID- 15557454
TI  - Microarray analysis of the failure of filtering blebs in a rat model of glaucoma
      filtering surgery.
AB  - PURPOSE: To generate data concerning changes in levels of protein expression
      associated with wound healing and bleb failure in a rat model of glaucoma
      filtration surgery (GFS), and to identify factors that may play a role in this
      process. METHODS: Of 36 Sprague-Dawley rats, GFS was performed on 27 by
      introducing a silicone cannula through a scleral tunnel under a conjunctival
      flap, resulting in aqueous-filtering blebs that failed over 8 to 13 days. The
      additional nine rats were used as the nonsurgical control. Nine blebs were
      harvested at each of days 0, 2, 5, and 12 and pooled, yielding three replicates
      of three blebs per time point. RNA was extracted, labeled, and hybridized to 230A
      rat GeneChip arrays (Affymetrix, Santa Clara, CA). RESULTS: Of the 15,924 probe
      sets/genes present on the array, 923 genes were indicated to have a significant
      treatment effect at P < 0.005. Eight gene expression clusters were identified
      that could be broadly classified into three basic patterns. These were an
      increase on day 2, a decrease on day 2, or an increase on either day 5 or 12. The
      greatest change occurred between days 0 and 2. The most heavily populated
      functional categories included growth factors, structural proteins, and matrix
      metalloproteinases. CONCLUSIONS: This study represents the first large-scale gene
      expression analysis after GFS. Expression patterns for known mediators of the
      bleb scarring process, including transforming growth factor-beta, connective
      tissue growth factor, and matrix metalloproteinases, were confirmed, and a number
      of mediators not previously associated with this process were identified.

PMID- 15557455
TI  - Focal adhesion kinase overexpression induces enhanced pathological retinal
      angiogenesis.
AB  - PURPOSE: Focal adhesion kinase (FAK) is involved in processes integral to
      angiogenesis, such as cell growth, survival, and migration. FAK is activated by
      angiogenic growth factors, such as insulin-like growth factor (IGF)-I, vascular
      endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The
      study was conducted to determine whether overexpression of FAK or FAK-related
      nonkinase (FRNK), an inhibitor of FAK, could influence human retinal endothelial
      cell (HREC) migration and in vivo angiogenesis. METHODS: Migration in response to
      a combination of growth factors was examined in transfected HRECs overexpressing
      FAK or FRNK. The effect of FAK or FRNK overexpression on preretinal
      neovascularization was examined in a mouse model of oxygen-induced retinopathy.
      RESULTS: Overexpression of FAK in HRECs resulted in a 102% +/- 13% increase (P =
      1.4 x 10(-4)) in cell migration, whereas overexpression of FRNK resulted in a 20%
      +/- 8% decrease (P = 0.01). Overexpression of FAK in mouse eyes led to formation
      of numerous large vascular tufts resembling glomeruli and a 57% +/- 7% increase
      in preretinal neovascularization (P = 3 x 10(-9)), whereas FRNK resulted in a 55%
      +/- 15% reduction (P = 5 x 10(-5)). CONCLUSIONS: Modulating the FAK/FRNK system
      may provide a novel approach to inhibiting pathologic retinal angiogenesis.

PMID- 15557456
TI  - Fundus autofluorescence and fundus perimetry in the junctional zone of geographic
      atrophy in patients with age-related macular degeneration.
AB  - PURPOSE: To investigate retinal sensitivity in the junctional zone of geographic
      atrophy (GA), with variations in fundus autofluorescence (FAF) in patients with
      advanced age-related macular degeneration (AMD). METHODS: The spatial
      distribution and intensity of FAF were recorded with a confocal scanning laser
      ophthalmoscope (SLO). Eyes had normal background FAF (group 1) or increased FAF
      (group 2) surrounding the atrophic patches. Retinal sensitivity was assessed by
      applying light stimuli with static automated full-threshold fundus perimetry with
      a modified SLO. Threshold sensitivities were compared with age-matched normal
      sensitivities. RESULTS: Thirty-nine eyes of 39 patients with GA were included.
      Group 2 had a higher percentage of all test points outside the GA area, with
      decreased retinal sensitivity (44.9% +/- 28.7%) compared with group 1 (20.7% +/-
      12.7%; P = 0.0063; multiple regression model; outcome variable is retinal
      sensitivity; covariates are group affiliation and GA area). Within group 2, the
      average percentage of stimuli in areas of normal FAF with reduced sensitivity was
      38.0% +/- 33.0%, whereas the average percentage of stimuli in areas of elevated
      FAF with reduced sensitivity was 52.6% +/- 29.7% (P = 0.023, Wilcoxon signed rank
      test). CONCLUSIONS: Areas of increased FAF outside GA may be associated with
      variable degrees of loss of retinal sensitivity and suggest a functional
      correlate of excessive accumulation of retinal pigment epithelium lipofuscin in
      AMD. Combining in vivo recording of FAF and retinal sensitivity, using SLO
      technology, may give important clues in the understanding of mechanisms of
      disease.

PMID- 15557457
TI  - Aquaporin-4 gene disruption in mice protects against impaired retinal function
      and cell death after ischemia.
AB  - PURPOSE: Water channel aquaporin (AQP)-4 is expressed in Muller cells in retina,
      which are similar to astroglial cells in the central nervous system, where AQP4
      deletion protects against cytotoxic brain edema after cerebral ischemia. A
      transient ischemia-reperfusion model was used to determine whether AQP4 deletion
      in mice protects the retina. METHODS: Retinal function and morphology were
      assessed in wild-type versus AQP4-deficient mice after ischemic damage produced
      by a 45- to 60-minute elevation of intraocular pressure to 120 mm Hg. Retinal
      function was assessed by electroretinography, and retinal structure by light
      microscopy. Extracellular space (ECS) size in fluorescently stained retinal
      slices was assessed by fluorescence recovery after photobleaching. RESULTS:
      Retinal function and cell survival were significantly improved in AQP4-deficient
      mice in both inbred (C57/bl6) and outbred (CD1) genetic backgrounds. By
      electroretinography, b-wave amplitude was reduced by 75% to 83% at 1 to 4 days
      after ischemia in wild-type mice versus 48% to 51% in AQP4-null CD1 mice.
      Reductions were 53% to 72% versus <34% in C57/bl6 mice. Retinal structure and
      cell count were preserved in AQP4-null mice, particularly in the inner nuclear
      and plexiform layers of the retina, where Muller cells are concentrated. At 4
      days after ischemia, inner retinal thickness was thinned by 43% in wild-type mice
      versus 11% in AQP4-null mice. Several mechanisms for retinal protection were
      investigated, including ECS expansion, reduced early swelling, and altered Kir4.1
      K(+) channel expression. CONCLUSIONS: AQP4 deletion in mice is neuroprotective in
      a transient ischemia model of retinal injury, suggesting the possible use of AQP4
      inhibitors in retinal vascular occlusive and ischemic diseases.

PMID- 15557458
TI  - The Minnesota Grading System of eye bank eyes for age-related macular
      degeneration.
AB  - PURPOSE: The Minnesota Grading System (MGS) is a method to evaluate human eye
      bank eyes and determine the level of age-related macular degeneration (AMD), by
      using criteria and definitions from the Age-Related Eye Disease Study (AREDS).
      METHODS: Donor eyes (108 pairs) from the Minnesota Lions Eye Bank were cut
      circumferentially at the pars plana to remove the anterior segment. A 1000 +/-
      2.5-microm ruby sphere was placed on the optic nerve as a size reference. A
      digital, high-resolution, color macular photograph was taken through a dissecting
      microscope. The neurosensory retina was removed from one globe of the pair. The
      underlying retinal pigment epithelium was rephotographed, localizing the fovea
      with a proportional triangle. A grid was superimposed in the macular photographs
      and images were graded according to AREDS criteria. Twenty pairs were dissected
      bilaterally and graded for symmetry. RESULTS: Eighty-eight globes were graded
      into one of four MGS categories. Nineteen (95%) of 20 globes had symmetric
      grades. CONCLUSIONS: The MGS provides a methodology to grade donor tissue from
      eye bank eyes to correspond to the AREDS classification system. Donor tissue may
      be used for subsequent molecular analysis, including genomics and proteomics.

PMID- 15557459
TI  - Stimulation of neovascularization by the anti-angiogenic factor PEDF.
AB  - PURPOSE: Examine the effect of (pigment epithelium-derived growth factor; PEDF)
      on laser-induced choroidal neovascularization (CNV). METHODS: Adult C57Bl/6 mice
      were anesthetized and four laser spots were placed in each quadrant of the fundus
      with a krypton red laser (614 nm, 50 microm, 0.05 second, 200 mW). Animals were
      treated with various doses of PEDF administered with miniosmotic pumps implanted
      subcutaneously. Seven days after laser treatment, mice were perfused with 3% FITC
      high-molecular-weight dextran, the eyes enucleated, and neovascularization
      analyzed by confocal microscopy. Data were recorded as the volume of the
      neovascular complex. The effect of PEDF on endothelial cell migration, vascular
      tube formation in synthetic basement membrane, and VEGF production was also
      determined. RESULTS: Mice receiving a lower dose of PEDF (90 microg/mL) had
      significantly decreased areas of CNV. A high dose of PEDF (360 microg/mL)
      significantly increased CNV, whereas an intermediate dose (180 microg/mL) of PEDF
      had no effect. PEDF inhibited endothelial cell migration and vascular tube
      formation at lower doses (0.5-5 microg/mL). High doses of PEDF (25-50 microg/mL)
      stimulated endothelial cell migration, enhanced vascular tube formation in vitro,
      and stimulated VEGF production from endothelial cells. Neutralizing anti-VEGF
      antibody completely reversed the stimulatory effects of high doses of PEDF on CNV
      in vivo. CONCLUSIONS: PEDF demonstrates opposing effects on CNV and endothelial
      cell function. Whereas low doses are inhibitory, high doses can augment the
      development of the neovasculature. These results suggest that the effects of PEDF
      on neovascularization are more complex than originally believed and that caution
      should be exercised when PEDF therapies are considered.

PMID- 15557460
TI  - Genetic linkage of snowflake vitreoretinal degeneration to chromosome 2q36.
AB  - PURPOSE: To identify the chromosomal location of the gene causing snowflake
      vitreoretinal degeneration (SVD), an autosomal dominant retinal degeneration
      characterized by small yellow-white dots in the retina, fibrillar anomaly of the
      vitreous humor, and retinal detachment. METHODS: Clinical data were collected on
      31 family members by history and examination. Thirteen family members underwent
      prospective examination. Genotyping was performed using microsatellite markers
      spaced at approximately 10 cM intervals. Two-point and multipoint linkage
      analysis was performed (FASTLINK version of the MLINK program and the VITESSE
      algorithm, both available at http://linkage.rockefeller.edu/soft/list.html).
      Direct DNA sequencing of amplified genomic DNA and mRNA was performed for
      candidate gene analysis. RESULTS: The SVD locus was linked to markers in a region
      of chromosome 2q36 defined by D2S2158 and D2S2202, based on meiotic breakpoint
      mapping of affected individuals. A maximum two-point lod score of 5.5 was
      obtained with marker D2S172 at theta; = 0 within this region. Direct DNA
      sequencing of all 52 exons of the COL4A3 gene revealed no potentially pathogenic
      coding sequence variation or evidence for deletion. CONCLUSIONS: The genetic
      locus for SVD lies in a 9 Mb region flanked by D2S2158 and D2S2202. Localization
      of SVD to a genomic region distinct from both Wagner disease and the Stickler
      syndromes indicates that SVD is a distinct genetic entity. The absence of coding
      sequence variation in the only collagen gene within the disease-region, suggests
      a novel pathogenesis for vitreoretinal degeneration. Snowflake vitreoretinal
      degeneration should be considered in the differential diagnosis of families with
      fibrillar anomaly of the vitreous.

PMID- 15557461
TI  - Differences in pulsatile ocular blood flow among three classifications of
      diabetic retinopathy.
AB  - PURPOSE: Choroidal blood flow may be determined by pulsatile ocular blood flow
      (POBF) measurements. In the present study, the POBF of diabetic patients with
      increasingly severe retinopathy was compared with that in nondiabetic control
      subjects. METHODS: The study was a masked cross-sectional analysis. Seventy-seven
      diabetic subjects, including 13 with mild or no retinopathy, 36 with moderate to
      severe retinopathy, and 28 with proliferative diabetic retinopathy (PDR),
      previously treated with panretinal photocoagulation (PRP). Fifty-six nondiabetic
      control subjects served as the comparison group. All subjects underwent masked
      measurement of POBF in the right eye by Langham pneumotonometry. Analysis of
      variance (ANOVA) determined whether differences existed between groups. Pair-wise
      comparisons between groups were conducted by Student's t-test. RESULTS: The main
      outcome measures were ophthalmic pulse amplitudes, intraocular pressure (IOP),
      heart rate, and POBF. Patients with moderate to severe nonproliferative diabetic
      retinopathy (NPDR) had POBF 18% higher than the control (mean OBF, 943
      microL/min). Among PRP-treated subjects with PDR, ocular blood flow was 22% below
      the control (mean OBF, 619 microL/min), and 34% less than moderate to severe
      nonproliferative diabetic retinopathy. Diabetic patients with no retinopathy or
      mild NPDR had OBF indistinguishable from the control (785 vs. 797 microL/min).
      Differences between the four groups were statistically significant by ANOVA (P <
      0.0001). CONCLUSIONS: POBF is unaffected early in diabetic retinopathy, but
      increases significantly in eyes with moderate to severe NPDR. POBF is decreased
      in eyes with laser-treated PDR. These experimental data represent the largest
      published assessment of POBF in NPDR. This is the first study to examine POBF in
      subjects with PRP-treated PDR.

PMID- 15557462
TI  - Contrast sensitivity deficits in inferred magnocellular and parvocellular
      pathways in retinitis pigmentosa.
AB  - PURPOSE: To define the contrast sensitivity deficits of patients with retinitis
      pigmentosa (RP) under testing conditions designed to emphasize threshold
      mediation by either the magnocellular (MC) or parvocellular (PC) pathway. METHOD:
      Contrast sensitivity was measured with spatially localized, narrow-band test
      patterns at peak spatial frequencies ranging from 0.25 to 8 cycles per degree
      (cpd), using a steady-pedestal paradigm (brief presentation of the test stimulus
      against a continuously presented luminance pedestal) and a pulsed-pedestal
      paradigm (simultaneous brief presentation of the test stimulus and luminance
      pedestal) to favor the MC and PC pathways, respectively. The contrast sensitivity
      functions of 12 patients with RP who had visual acuities ranging between 20/12.5
      and 20/40 were compared to those of 10 visually normal, age-equivalent control
      observers. RESULTS: Five of the patients with RP who had Snellen visual acuities
      better than 20/25 had contrast sensitivity functions that were within the normal
      limits at all spatial frequencies for both testing paradigms. The other seven
      patients with RP had reduced contrast sensitivities for both paradigms, with the
      greatest reduction in sensitivity occurring at the highest spatial frequency.
      Their contrast sensitivity deficits were equivalent for the steady- and pulsed
      pedestal paradigms. CONCLUSIONS: As observed in previous studies, the degree of
      contrast sensitivity loss shown by the patients with RP was greatest at the
      highest stimulus spatial frequency. However, in comparison to prior studies of
      contrast discrimination in patients with RP, there was no evidence of a
      preferential contrast sensitivity loss within the MC pathway. This apparent
      discrepancy is attributed to differences in the test targets and psychophysical
      judgments that were used in the studies, which emphasizes the importance of task
      characteristics in evaluating relative deficits within the MC and PC processing
      streams in visual disorders.

PMID- 15557463
TI  - Iris pigment epithelium attachment to aged submacular human Bruch's membrane.
AB  - PURPOSE: To determine whether iris pigment epithelium (IPE) cells can attach to
      aged submacular human Bruch's membrane and to assess whether IPE cells express
      the integrin subunits that may be necessary to bind to the known extracellular
      matrix ligands present in Bruch's membrane. METHODS: IPE cells were seeded onto
      the RPE basement membrane (RPEbm) or inner collagenous layer (ICL) of aged
      submacular Bruch's membrane as microaggregates or were expanded in culture until
      enough cells could be obtained for seeding. Cell morphology and the percentage of
      cell coverage were determined 1 or 7 days after seeding. Messenger RNA was
      extracted from cultured and uncultured IPE cells and analyzed by RT-PCR. The
      expression of integrin subunits alpha1 to alpha6 and beta1 mRNA was examined.
      RESULTS: Coverage by uncultured IPE was low on both surfaces at day-1 (RPEbm,
      7.9% +/- 4.8%; ICL, 5.0% +/- 2.5%) with few intact cells present. Culturing IPE
      improved attachment with similar coverage on both surfaces and no significant
      difference between day-1 (RPEbm, 89.9% +/- 9.1%; ICL, 63.4% +/- 26.5%) and day-7
      (RPEbm, 97.8% +/- 2.3%; ICL, 94.7% +/- 6.6%). By day-7, cell morphology and
      coverage on both surfaces was variable, ranging from few intact cells to a high
      degree of coverage by flattened cells. All integrin subunits studied were
      expressed in cultured cells, whereas alpha2, alpha3, and alpha4 showed less or no
      expression in uncultured cells. CONCLUSIONS: Upregulation of integrin mRNA
      expression may be one explanation for the difference in coverage by cultured
      versus uncultured IPE cells. The presence of dead, dying, or flattened cells at
      day 7 indicates that IPE may not survive or differentiate on aged submacular
      Bruch's membrane.

PMID- 15557464
TI  - Taurine uptake by human retinal pigment epithelium: implications for the
      transport of small solutes between the choroid and the outer retina.
AB  - PURPOSE: To characterize the Michaelis-Menten kinetics of the taurine transporter
      (TT) in retinal pigment epithelium (RPE) freshly isolated from human donor eyes.
      To identify the rate limiting compartment in the pathway of taurine delivery from
      the choroidal blood supply to the outer retina composed by Bruch's-choroid (BC)
      and the RPE in the human older age group. METHODS: In human donor samples (4
      melanoma-affected eyes, and 14 control eyes; age range, 62-93 years),
      radiochemical techniques were used to determine the RPE taurine accumulation at
      various exogenous concentrations. The transport capability of human RPE was
      obtained from a kinetic analysis of the high-affinity carrier over a substrate
      concentration of 1 to 60 microM taurine. RESULTS: Uptake of taurine into human
      RPE at a taurine concentration of 1 microM was independent of donor age (P >
      0.05) and averaged at 2.83 +/- 0.27 (SEM) pmol/10 minutes per 6-mm trephine.
      Taurine transport by human RPE was mediated by a high-affinity carrier of K(m) 50
      microM and V(max) of 267 pmol/10 minutes per 5-mm disc. CONCLUSIONS: In human
      donor RPE, uptake of taurine remained viable in the age range 62 to 93 years.
      Taurine transport rates in the RPE were lower than across the isolated BC
      complex, and thus the data suggest that the former compartment houses the rate
      limiting step in the delivery of taurine to the outer retina.

PMID- 15557465
TI  - Muller cell production of insulin-like growth factor-binding proteins in vitro:
      modulation with phenotype and growth factor stimulation.
AB  - PURPOSE: Muller cells are present in diabetic fibrocontractive ocular tissues and
      generate tractional forces in response to insulin-like growth factors. Recent
      studies indicate that diabetes-associated increases in vitreous insulin-like
      growth factor activity are, in part, attributable to changes in insulin-like
      growth factor binding proteins (IGFBPs). The objectives of this study were to
      evaluate Muller cells as a source of IGFBPs and characterize changes associated
      with cell phenotype and growth factor stimuli known to be present in diabetic
      vitreous. METHODS: Muller cells isolated from normal porcine retina were
      maintained in culture for 1 and 5 weeks, yielding phenotypes described as
      proliferative and myofibroblastic. RNA preparations from porcine liver, retina,
      and Muller cell cultures were evaluated by RT-PCR and Northern blot analysis.
      IGFBP production was verified by Western ligand and Western blot analysis of
      Muller-cell-conditioned media and detergent-extracted proteins. RESULTS:
      Molecular biological analyses of RNA from normal retina and from proliferative
      and myofibroblastic Muller cells did not detect message for IGFBP-1, but revealed
      progressive increases in message abundance for IGFBP-2, -3, -4, and -6. IGFBP-5
      message was detected in all samples, but was least abundant in myofibroblastic
      Muller cells. Stimulation of myofibroblastic Muller cells by IGF-I and -II, but
      not PDGF, further increased message abundance and production of IGFBP-2, -4, -5,
      and -6, but not IGFBP-3. CONCLUSIONS: Muller cell production of IGFBPs changes
      with phenotype and, in most cases, is highest in the cells most likely to
      participate in fibrocontractive retinal disease. IGFBP production by these cells
      is further increased by IGF-I and -II, growth factors known to be present and
      active in proliferative vitreoretinal disorders, suggesting that Muller cells
      represent a potential source of vitreous IGFBPs in disorders involving this cell
      type.

PMID- 15557466
TI  - Retinopathy in monkeys with spontaneous type 2 diabetes.
AB  - PURPOSE: Type 2 diabetes occurs spontaneously in rhesus monkeys and shows an
      extraordinary similarity to human diabetes in clinical features and relative time
      course. The purpose of this study was to investigate clinically and
      histopathologically the ocular changes in these monkeys. METHODS: Ophthalmoscopic
      examinations were performed on aged normal and diabetic monkeys. Retinas from 16
      diabetic monkeys and 6 nondiabetic monkeys were incubated postmortem for
      adenosine diphosphatase (ADPase) activity (labels viable retinal blood vessels)
      and flat-embedded in JB-4. Tissue sections were cut through areas of interest.
      RESULTS: Cotton-wool spots, intraretinal hemorrhages, and hard exudates in the
      macula were observed by ophthalmoscopy in some diabetic monkeys. Dot/blot
      hemorrhages, cotton-wool spots, and small nonperfused areas were the earliest
      histologically documented changes in the retinas. Large nonperfused areas
      extending from optic disc to midfovea were observed in four diabetic monkeys.
      Formation of small intraretinal microvascular abnormalities (IRMAs) and
      microaneurysms were associated with the areas of nonperfusion. There were
      apparent fluid-filled spaces in the outer plexiform layer in three of these
      maculas, suggesting macular edema. There was a significant correlation between
      the occurrence of retinopathy and hypertension (P = 0.037 for systolic pressure;
      P = 0.019 for diastolic pressure). In elastase-digested retinas, the ratio of
      pericytes to endothelial cells was 0.66:1 in diabetic and 0.64:1 in nondiabetic
      (P = 0.75) retinas. CONCLUSIONS: This is the first detailed analysis of
      retinopathy in a colony of spontaneous type 2 diabetic monkeys. Monkeys with type
      2 diabetes have many of the angiopathic changes associated with human diabetic
      retinopathy. Hypertension correlates with the severity of the diabetic
      retinopathy.

PMID- 15557467
TI  - Expression of class-3 semaphorins and their receptors in the neonatal and adult
      rat retina.
AB  - PURPOSE: Semaphorins comprise a family of molecules that influence the growth and
      guidance of neuronal processes. Class-3 semaphorins are secreted proteins, and
      their effects are mediated by neuropilin (NP) and plexin (Plx) receptors. There
      is considerable information on mechanisms that influence axonal guidance and
      plasticity in the mammalian visual system, but a role for semaphorins has
      received less scrutiny. The purpose of the current study was to survey class-3
      semaphorin and cognate receptor expression in young and adult rat retinas.
      METHOD: The mRNA expression of five class-3 semaphorins (3A, 3B, 3C, 3E, and 3F)
      and receptor subtypes NP-1 and -2 and plexins A1 and A2 was determined, by using
      riboprobes and in situ hybridization on cryosections of newborn (postnatal day
      [P]0), juvenile (P14), and adult rat retinas. Retinal ganglion cells (RGCs) were
      identified by retrograde labeling after injections of a fluorescent tracer
      (Fluorogold, FG) into the superior colliculus. Hybridized sections were also
      immunostained to identify specific retinal cell classes. RESULTS: mRNA expression
      for all five members of the class-3 semaphorin family was seen in adult FG
      labeled RGCs. Qualitatively, expression was highest for semaphorins 3B and 3C,
      and lowest for 3A. Levels of mRNA expression in RGCs were lower in newborn
      retinas but were adult-like by P14. Expression by different cell types in the
      inner nuclear layer was also seen, especially at P14. Expression of NP-2 and
      PlxA2 mRNAs was evident in developing inner nuclear and ganglion cell layers at
      birth. Expression increased postnatally and was maintained into adulthood. NP-1
      and PlxA1 expression was also present, but at comparatively lower levels.
      CONCLUSIONS: The presence of class-3 semaphorins and their receptors in neonatal
      and adult rat retina suggests a potential role for these proteins in retinal
      development and in the maturation, stabilization, and plasticity of mammalian
      primary visual pathways.

PMID- 15557468
TI  - FAS-mediated apoptosis and its relation to intrinsic pathway activation in an
      experimental model of retinal detachment.
AB  - PURPOSE: To determine whether the FAS-mediated apoptosis pathway becomes
      activated in the retina after retinal detachment and to investigate the temporal
      relationship between the activation of the FAS-pathway and the intrinsic
      apoptosis pathway involving caspase-9 and cytochrome c. METHODS: Experimental
      retinal detachments were created in Brown-Norway rats by injecting 10% hyaluronic
      acid into the subretinal space. Retinal tissue was harvested at 2, 4, 8, 24, 72,
      and 168 hours after creation of the detachment. Immunoprecipitation was performed
      to assess for FAS-receptor/FAS-ligand complex formation, and activation of
      caspase-8 and BID (a member of the Bcl-2 family of proteins) was assessed by
      Western blot analysis. A caspase-9 activity assay and immunoprecipitation of the
      caspase-9/cytochrome c complex were performed at these same time points. Specific
      pathway inhibition was performed with the caspase-9 inhibitor zLEHD.fmk or
      neutralizing antibodies against either the FAS-receptor or FAS-ligand.
      Transcription levels of FAS and intrinsic pathway intermediates were assessed as
      a function of time after retinal detachment by using quantitative real-time
      polymerase chain reaction. RESULTS: Retinal detachment resulted in the time
      dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak
      of caspase-9 activity and caspase-9/cytochrome c complex formation. Cleavage of
      caspase-8 and truncation of BID were also observed. Injection of zLEHD.fmk into
      the subretinal space of a detached retina resulted in decreased caspase-9
      activity, as did injection of anti-FAS-receptor antibody into either the
      subretinal space or the vitreous. Retinal detachment resulted in the
      transcriptional upregulation of the FAS-receptor, FAS-ligand, caspase-8 and BID,
      but not caspase-9 and cytochrome c. CONCLUSIONS: The FAS-mediated apoptosis
      pathway becomes activated and transcriptionally upregulated after retinal
      detachment. The peak of FAS activation precedes that of the intrinsic pathway,
      and inhibition of FAS activation can decrease caspase-9 activity.

PMID- 15557469
TI  - Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived
      from adult iris and ciliary tissue.
AB  - PURPOSE: It remains unclear which gene induction effectively generates
      photoreceptor-specific phenotypes from nonretinal tissues. The purpose of this
      study was to determine whether Crx and Otx2--homeobox genes related to
      photoreceptor development--can induce the generation of these phenotypes in cells
      derived from adult ciliary and iris tissue and in mesencephalon-derived neural
      stem cells. METHODS: Crx and Otx2 were transferred into adult rat ciliary- and
      embryonic mesencephalon-derived neurospheres and adult rat iris-derived cells
      with the aid of a recombinant retrovirus. The presence of photoreceptor-specific
      phenotypes was confirmed by immunocytochemistry and Western blot analysis.
      RESULTS: More than 90% of the Crx- and Otx2-transfected ciliary- and iris-derived
      cells exhibited rod opsin immunoreactivity, whereas few of the similarly
      transfected mesencephalon-derived neural stem cells expressed rod opsin. At least
      two additional key components of the phototransduction cascade, recoverin and
      Gdeltat1, were expressed by Crx- and Otx2-transfected iris-derived cells.
      CONCLUSIONS: Crx and Otx2 effectively induced the generation of photoreceptor
      specific phenotypes from ciliary- and iris-derived cells. That both Crx and Otx2
      induced phenotype generation in cells derived from iris or ciliary tissue may
      suggest an approach to photoreceptor cell preparation for retinal
      transplantation.

PMID- 15557470
TI  - Susceptibilities to and mechanisms of excitotoxic cell death of adult mouse inner
      retinal neurons in dissociated culture.
AB  - PURPOSE: To explore the susceptibilities of adult retinal neurons in dissociated
      culture to treatments with excitotoxic agonists and the mechanisms of the
      resultant retinal cell death. METHODS: C57B6 mice were used. Retinas were
      removed, dissociated, plated on a polylysine/laminin substrate, and maintained in
      vitro for 5 to 7 days. Excitotoxic agonists (glutamate, N-methyl-D-aspartate
      [NMDA], or kainic acid [KA]) were added for 30 minutes or 24 hours, sometimes in
      the presence of modified extracellular ion concentrations or potential blocking
      agents. The next day, cells were fixed and immunocytochemically stained to
      identify ganglion and amacrine cells. Surviving cells were counted. RESULTS:
      Ganglion cells from adult mouse retinas were much less susceptible to excitotoxic
      death than those prepared from neonatal retinas. Adult amacrine cells were killed
      by KA, NMDA, or glutamate. Experiments with selective blockers demonstrated that
      KA killed through AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
      receptors, whereas NMDA and glutamate exerted toxicity through a combination of
      AMPA and NMDA receptors. The KA-induced death of amacrine cells was not mediated
      by chloride ions. Removal of extracellular sodium, however, completely prevented
      the amacrine cell death, and removal of extracellular calcium prevented
      approximately 70% of the death. The path of calcium entry was investigated.
      Experiments with selective blockers indicated that the lethal calcium entry was
      via reverse operation of a sodium-calcium exchanger. CONCLUSIONS: There is a
      profound developmental regulation in the sensitivity of retina ganglion cells to
      excitotoxic insults. Excessive intracellular sodium and calcium are the proximal
      causes of amacrine cell death. The pathologic calcium entry is dependent on the
      sodium overload, which then drives a sodium-calcium exchanger to take up calcium.

PMID- 15557472
TI  - Paired-flash identification of rod and cone dysfunction in the diabetic rat.
AB  - PURPOSE: To investigate the onset of retinal neural dysfunction in the
      streptozotocin (STZ)-induced diatebic rat. METHODS: A cohort of 20 Sprague-Dawley
      rats were randomly assigned to treatment (STZ 50 mg/kg, n = 10) and control
      (citrate buffer, n = 10) groups and observed for 12 weeks. Diabetes was confirmed
      by blood glucose (>15 mmol/L) and HBA(1c) (>7.0%). Treated animals received 2 to
      3 U insulin daily. Retinal function was monitored using paired-flash
      electroretinograms (ERGs) at baseline and various time points between 2 days and
      12 weeks after treatment, to allow isolation of rod and cone components.
      Protocols compared photoreceptor and inner retinal responses (rod and cone) at
      each time point. RESULTS: Losses in the function of rod photoreceptors and the
      inner retina were seen 2 days after STZ injection, with recovery in some
      components by 4 weeks and a secondary loss of function at 12 weeks. Some inner
      retinal responses (cone response and rod oscillatory potentials (OPs) remained
      consistently depressed over the entire 12 weeks. CONCLUSIONS: Retinal neural
      dysfunction was observed as early as 2 days after STZ injection. These acute
      changes reflect either STZ toxicity or hyperglycemia as a result of pancreatic
      compromise. Consistent loss over the 12 weeks of the cone response and OPs
      suggests a vulnerability of the inner retina to STZ-related effects. The 12-week
      losses in function of retinal neurons are consistent with a generalized diabetic
      neuropathy, since impaired function developed simultaneously in both inner and
      outer retinal neurons.

PMID- 15557471
TI  - Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization.
AB  - PURPOSE: The purpose of the study was to characterize signaling intermediates
      involved in angiogenic responses of retinal endothelial cells (RECs) to the
      extracellular matrix and growth factors, by using specific inhibitors. METHODS:
      Tubelike structure formation and the development of secondary sprouts on a
      basement membrane (BM) matrix, cell proliferation, and cell migration were
      studied in cultures of bovine and human RECs. Specific inhibitors were tested for
      inhibition of retinal neovascularization in a mouse model of oxygen-induced
      retinopathy (OIR). RESULTS: In initial experiments, the broad-spectrum protein
      kinase inhibitors, H7 and H89, stabilized REC tubes on BM matrix and inhibited
      secondary sprouting, cell migration, and cell proliferation. Among more specific
      kinase inhibitors tested, only inhibitors of protein kinase CK2 (formerly, casein
      kinase II), such as emodin and DRB, were able to duplicate the effects of H7 and
      H89. Actinomycin D caused only minor changes in angiogenic assays, suggesting
      that CK2's effects on REC did not involve its known impact on transcription. The
      extent of retinal neovascularization in a mouse OIR model was reduced >70%
      (versus untreated or vehicle-treated groups) after treatment with emodin (6 days
      at 60 mg/kg per day) and by approximately 60% after treatment at the same dose
      with TBB, the most specific CK2 inhibitor known. In the treated retinas, the main
      vascular tree had minimal changes, but the neovascular tufts were greatly reduced
      in number or absent. CONCLUSIONS: This is the first demonstration of the
      involvement of ubiquitous protein kinase CK2 in angiogenesis. Naturally derived
      CK2 inhibitors may be useful for treatment of proliferative retinopathies.

PMID- 15557473
TI  - Adaptive optics simulation of intraocular lenses with modified spherical
      aberration.
AB  - PURPOSE: Adaptive optics systems can be used to investigate the potential visual
      benefit associated with correcting ocular wave-front aberration. In this study,
      adaptive optics techniques were used to evaluate the potential advantages and
      disadvantages associated with intraocular lenses (IOLs) with modified spherical
      aberration profiles. METHODS: An adaptive optics vision simulator was constructed
      that allows psychophysical tests to be performed while viewing targets through
      any desired ocular wave-front profile. With this simulator, the subjective visual
      performance of four subjects was assessed by letter acuity and contrast
      sensitivity (at 3, 6, and 15 cyc/deg) for two different values of induced
      spherical aberration. The values of spherical aberration were chosen to reproduce
      two conditions: the average amount measured in pseudophakic patients with
      implanted IOLs having spherical surfaces and the complete correction of the
      individual's spherical aberration. Visual performance was assessed in both white
      and green light, at best focus and for defocus of +/-0.5 and +/-1.0 D. RESULTS:
      There was an average improvement in visual acuity associated with the correction
      of spherical aberration of 10% and 38% measured in white and green light,
      respectively. Similarly, average contrast sensitivity measurements improved 32%
      and 57% in white and green light. When spherical aberration was corrected, visual
      performance was as good as or better than for the normal spherical aberration
      case for defocus as large as +/-1 D. CONCLUSIONS: Correcting ocular spherical
      aberration improves spatial vision in the best-focus position without
      compromising the subjective tolerance to defocus.

PMID- 15557474
TI  - Rapid quantification of adult and developing mouse spatial vision using a virtual
      optomotor system.
AB  - PURPOSE: To develop a simple, rapid method of quantifying the spatial vision of
      mice. METHODS: A rotating cylinder covered with a vertical sine wave grating was
      calculated and drawn in virtual three-dimensional (3-D) space on four computer
      monitors facing to form a square. C57BL/6 mice standing unrestrained on a
      platform in the center of the square tracked the grating with reflexive head and
      neck movements. The spatial frequency of the grating was clamped at the viewing
      position by repeatedly recentering the cylinder on the head. Acuity was
      quantified by increasing the spatial frequency of the grating until an optomotor
      response could not be elicited. Contrast sensitivity was measured at spatial
      frequencies between 0.03 and 0.35 cyc/deg. RESULTS: Grating acuity was measurable
      on the day of eye opening (postnatal day [P]15: mean acuity, 0.031 cyc/deg) and
      reached a maximum (approximately 0.4 cyc/deg) by P24. A peak in the contrast
      sensitivity function emerged on P16 (4.7, or 21% contrast at 0.064 cyc/deg). The
      peak remained at 0.064 cyc/deg and climbed to a maximum sensitivity of 24.5, or
      4% contrast, by P29. Acuity was obtained in each mouse in <10 minutes, and a
      detailed contrast sensitivity curve was generated in approximately 30 minutes.
      CONCLUSIONS: The virtual optomotor system provides a simple and precise method
      for rapidly quantifying mouse vision. Behavioral measures of vision in mice are
      essential for interpreting the results of experiments designed to reveal the
      cellular and molecular mechanisms of vision and visual development and for
      evaluating potential treatments for visual diseases.

PMID- 15557476
TI  - Beyond exposure for posttraumatic stress disorder (PTSD) symptoms: broad-spectrum
      PTSD treatment strategies.
AB  - Although cases of posttraumatic stress disorder (PTSD) with comorbid disorders
      are common, the first generation of PTSD treatment approaches, including exposure
      and cognitive-behavioral therapy, generally ignore symptoms beyond those specific
      to PTSD. Optimum PTSD treatment outcome requires more comprehensive strategies,
      and the development and empirical testing of broader approaches is the focus of
      the articles that follow in this special issue. After providing some background
      on PTSD and PTSD treatment, this paper gives an overview of these treatment and
      prevention papers, which represent second-generation strategies to help trauma
      exposed individuals.

PMID- 15557477
TI  - Exposure therapy for substance abusers with PTSD: translating research to
      practice.
AB  - Epidemiological research indicates that there is substantial comorbidity between
      posttraumatic stress disorder (PTSD) and substance use disorder (SUD). Moreover,
      there is growing evidence that having a comorbid PTSD diagnosis is associated
      with greater substance use problem severity and poorer outcomes from SUD
      treatment. In an attempt to improve the treatment outcome for individuals with
      PTSD-SUD, recently developed treatments combine exposure therapy for PTSD with an
      empirically supported treatment for SUD. This article describes one of the
      treatments and discusses treatment modifications that have been incorporated when
      translating this research-based therapy to practice in an inner-city community
      mental health center.

PMID- 15557478
TI  - Multicomponent behavioral treatment for chronic combat-related posttraumatic
      stress disorder: trauma management therapy.
AB  - Posttraumatic stress disorder(PTSD) is a severe and chronic mental disorder that
      is highly prevalent within Veterans Affairs (VA) Medical Centers. A severe
      psychiatric disorder, combat-related PTSD is typically accompanied by multiple
      comorbid psychiatric disorders, symptom chronicity, and extreme social
      maladjustment. Thus, PTSD is a complex psychiatric disorder resulting in
      considerable emotional distress and impaired social functioning and often
      constitutes a significant treatment challenge. Although a range of
      psychotherapeutic strategies for chronic PTSD have been advanced, behavioral
      treatments emphasizing various methods of exposure therapy have been the most
      carefully studied and show the most promise. However, chronic PTSD exposure alone
      does not appear to have a significant effect on the negative symptoms of PTSD
      (e.g., avoidance, interpersonal difficulties) or anger control. This may be
      because exposure is more focused on anxiety and fear reduction and does not
      address basic skill deficits, help reestablish impaired relationships, or teach
      anger control. Therefore, we developed a multicomponent treatment program to
      complement exposure by targeting those areas of the clinical syndrome (e.g.,
      social skills) not found to be helped by exposure alone. This treatment program,
      trauma management therapy (TMT), has showed good preliminary results in an open
      trial. In this article, we describe the treatment program, including elements of
      education, individually administered exposure therapy, programmed practice (i.e.,
      homework), and group-administered social and emotional skills training. The
      appendix includes a detailed description of how to implement the social and
      emotional skills training components on a session-by-session basis; the full TMT
      treatment manual is available on request.

PMID- 15557479
TI  - Multiple channel exposure therapy: combining cognitive-behavioral therapies for
      the treatment of posttraumatic stress disorder with panic attacks.
AB  - A large proportion of patients who present for treatment of posttraumatic stress
      disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what
      extent currently available PTSD treatment programs address this problem. Here we
      describe a newly developed treatment, multiple-channel exposure therapy (M-CET),
      for comorbid PTSD and panic attacks. The treatment utilizes elements of cognitive
      processing therapy treatment for PTSD and elements of panic control treatment to
      target physiological, cognitive, and behavioral symptoms. Preliminary results
      suggest that M-CET may provide a promising treatment program for a subset of
      patients with PTSD who experience panic attacks. In addition, guidelines for
      conducting M-CET with clients who have been exposed to diverse traumatic events
      are provided.

PMID- 15557480
TI  - Acceptance and commitment therapy in the treatment of posttraumatic stress
      disorder.
AB  - The current article describes the application of a behavioral psychotherapy,
      acceptance and commitment therapy (ACT), to the treatment of post-traumatic
      stress disorder (PTSD). It is argued that PTSD can be conceptualized as a
      disorder that is developed and maintained in traumatized individuals as a result
      of excessive, ineffective attempts to control unwanted thoughts, feelings, and
      memories, especially those related to the traumatic event(s). As ACT is a
      therapeutic method designed specifically to reduce experiential avoidance, it may
      be a treatment that is particularly suited for individuals with PTSD. The
      application of ACT to PTSD is described, and a case example is used to
      demonstrate how this therapy can be successfully used with individuals presenting
      for life problems related to a traumatic event.

PMID- 15557481
TI  - Community outreach program for child victims of traumatic events: a community
      based project for underserved populations.
AB  - Behavioral and cognitive behavioral treatment interventions have been shown to be
      effective for the treatment of trauma-related problems in children. However, many
      children and families in need of treatment do not have adequate access to
      services and do not have access to effective, evidence-based treatment services.
      The present article describes a community-based program that provides in-home and
      in-school treatment services, based on behavioral and cognitive behavioral
      approaches to addressing trauma-related emotional and behavioral problems in
      children.

PMID- 15557482
TI  - Description of an early intervention to prevent substance abuse and
      psychopathology in recent rape victims.
AB  - Approximately 683,000 adult women are raped each year. Only one in seven of these
      victims report the assault to police and receive forensic exams and other
      professional services. For many rape victims, this may be the only professional
      contact with service providers; however these services are typically limited to
      evidence collection and prophylactic STD treatment. Yet this exam also presents a
      unique opportunity for a preventive intervention to help prepare women to cope
      with potential stress related to rape-exam procedures and to address potential
      post rape psycho-pathology. This article reviews psychological interventions for
      trauma victims used in the acute post rape time frame and provides data from an
      ongoing clinical trial that evaluates delivery of a preventive intervention for
      victims presenting for forensic rape exams.

PMID- 15557483
TI  - Behavioral interventions for recent trauma: empirically informed practice
      guidelines.
AB  - Despite the successes in the treatment of chronic trauma-related distress, little
      attention has been devoted to developing behavioral interventions to be delivered
      soon after traumatic exposure in an effort to promote positive posttraumatic
      adjustment and to minimize the likelihood of enduring psychopathology. As a
      result, other forms of early intervention have filled this void and have been
      widely disseminated and applied, despite the lack of compelling evidence
      attesting to their efficacy. This article reviews the literature bearing on early
      interventions for trauma, including the encouraging outcomes of recently
      developed behavioral treatments. Empirically informed practice guidelines for
      intervening with recently traumatized individuals are presented. Future treatment
      development efforts will need to address an issue that has been largely neglected
      in traditional treatment models for traumatized populations-that of traumatic
      bereavement. Behavioral interventions may be particularly well-equipped to
      address this source of distress.

PMID- 15557485
TI  - Patient page. Long-term obesity is linked to loss of brain tissue.

PMID- 15557486
TI  - Does interferon beta help in secondary progressive MS?

PMID- 15557487
TI  - Turning on the heat: the search for febrile seizure genes.

PMID- 15557488
TI  - Cortical reorganization in the human brain: how the old dog learns depends on the
      trick.

PMID- 15557489
TI  - The neurological and cognitive sequelae of cardiac arrest.
AB  - BACKGROUND: Although cardiac arrest (CA) is commonly cited as a cause of amnesia,
      patients referred to the authors' center with a diagnosis of "amnesia" after CA
      rarely have isolated memory deficits. OBJECTIVE: To determine whether CA is a
      cause of pure amnesia and to assess patterns of cognitive deficits after CA.
      METHODS: The authors used cognitive assessment of 11 consecutive patients
      referred for memory deficits after CA, targeted at deficit domains identified in
      the literature reviews, and analysis of specific case reports and prospective
      studies of cognition after CA. RESULTS: The most common pattern of impairment in
      their patients was a combination of memory and motor deficits with variable
      executive impairment. No patient had isolated memory impairment. The case reports
      do not support the claim that isolated amnesia is a residual of CA; most cases of
      isolated amnesia are caused by subacute episodes of anoxia or excitotoxic injury.
      The prospective reports identify highly variable patterns of impairment, but
      isolated amnesia remains rare. CONCLUSIONS: Diffuse, sudden ischemic-hypoxic
      injury caused by cardiac arrest (CA) does not preferentially damage memory
      systems. Subacute or stepwise hypoxic or excitotoxic injury may cause isolated
      hippocampal injury and amnesia. The common pattern of impairment in the postacute
      phase after CA is a combination of memory, subtle motor, and variable executive
      deficits.

PMID- 15557490
TI  - Interferon beta-1b in secondary progressive MS: a combined analysis of the two
      trials.
AB  - BACKGROUND: A European (EU) and a North American (NA) placebo-controlled study
      with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis
      (SPMS) showed divergent results with regard to their primary outcome of sustained
      Expanded Disability Status Scale (EDSS) progression, while effects were similar
      on relapse and MRI-related endpoints. Reasons for this discrepancy were explored
      in the combined dataset. METHODS: Baseline characteristics and variability in
      EDSS assessments were compared. Retrospective combined analyses for time to
      confirmed progression were performed to assess treatment effects overall and in
      subgroups defined by pre-study disease activity criteria and other key baseline
      variables. RESULTS: The variance of EDSS measurements was 6.5% higher in the NA
      SPMS study. The EU study included patients in an earlier phase of SPMS and with
      more active disease both pre-study (relapses, MRI) as well as on study (EDSS,
      relapses, and MRI variables as assessed in the placebo groups). The pooled
      analysis showed an overall risk reduction by about 20% in patients treated with 8
      MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p = 0.008).
      Risk reduction by 30% to 40% was found for patients with at least one relapse or
      change in EDSS by >1 in the 2 years prior to study entry. No other consistent
      across-studies relation of clinical and MRI variables at baseline to potential
      treatment response was found. CONCLUSIONS: Although post hoc, this combined
      analysis of the two large studies with IFNB-1b in secondary progressive multiple
      sclerosis suggests that both pronounced disability progression and continuing
      relapse activity might help in identifying those patients in the secondary
      progressive phase of the disease who are more likely to benefit from treatment.

PMID- 15557491
TI  - Interferon beta-1b in secondary progressive MS: results from a 3-year controlled
      study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of interferon beta-1b (IFNbeta-1b)
      in subjects with secondary progressive multiple sclerosis (SPMS). METHODS: This 3
      year, multicenter, double-blind, placebo-controlled, randomized trial of IFNbeta
      1b included 939 subjects from the United States and Canada with SPMS and Expanded
      Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5. Subjects were
      randomly assigned to receive either placebo or IFNbeta-1b (250 microg or 160
      microg/m2 body surface area), administered subcutaneously every other day. The
      primary outcome was time to progression by > or =1.0 EDSS point (0.5 point if
      EDSS score was 6.0 to 6.5 at entry) confirmed at 6 months. Secondary outcomes
      included mean change in EDSS score from baseline, relapse-related measures, MRI
      activity, and a standardized neuropsychological function test. RESULTS: There was
      no significant difference in time to confirmed progression of EDSS scores between
      placebo-treated patients and either of the IFNbeta-1b treatment groups. However,
      IFNbeta-1b treatment resulted in improvement on secondary outcome measures
      involving clinical relapses, newly active MRI lesions, and accumulated burden of
      disease on T2-weighted MRI. Effects were similar for both IFNbeta-1b treatment
      groups. Neutralizing antibodies to IFNbeta-1b were detected in 23% of 250-microg
      and 32% of 160-microg/m2 recipients, but their presence did not consistently
      affect clinical or MRI outcomes. IFNbeta-1b was also well tolerated at both
      doses. CONCLUSIONS: Although no treatment benefit was seen on the time to
      confirmed progression of disability, relapse- and MRI-related outcomes showed
      significant benefit with both dosing regimens tested, a result consistent with
      the outcomes of earlier clinical trials.

PMID- 15557492
TI  - Prevalence of multiple sclerosis in a residential area bordering an oil refinery.
AB  - BACKGROUND: Community concerns about a potential excess of multiple sclerosis
      (MS) prompted this study. OBJECTIVE: To determine the period prevalence of MS in
      a community bordering a closed oil refinery and a control community. METHODS:
      Cases seen by a neurologist during 1998 to 2001 were obtained from area
      neurologists and hospital discharge data. Population data were obtained from the
      year 2000 US Census. Patient data were abstracted by a trained abstractor onto a
      standardized report form. A consulting neurologist reviewed the form and made a
      final diagnosis using the Poser criteria plus the category of presumed. Age
      adjusted prevalence rates and rates of agreement were calculated. RESULTS: The
      direct age-adjusted period prevalence for both sexes and all races for the entire
      study area was 113 per 100,000 (95% CI = 93 to 136). For white subjects only, the
      prevalence was 123 per 100,000 (95% CI = 102 to 147). With use of an indirect
      method of age adjustment, the number of observed cases in the community bordering
      the refinery was similar to the number of cases expected (standardized morbidity
      ratio = 130.8, 95% CI = 62.3 to 199.3), based on rates from the comparison area.
      The agreement between the treating neurologist (for definite plus probable cases)
      and the consulting neurologist (for definite plus probable plus presumed cases)
      was good (kappa = 0.5733). CONCLUSIONS: The prevalence of multiple sclerosis (MS)
      for this area was generally consistent with prevalence estimates calculated in
      previous studies in other areas. No significant excess was seen in the exposed
      area. MS was more prevalent in females than in males. The overall agreement
      between the consulting and treating neurologist was good.

PMID- 15557493
TI  - Linkage and association of febrile seizures to the IMPA2 gene on human chromosome
      18.
AB  - BACKGROUND: Febrile seizures (FSs) are the most common form of childhood
      seizures, and genetic factors play a role in susceptibility to FS. OBJECTIVE: To
      identify novel loci and genes associated with susceptibility to FS. METHODS:
      Study participants were the FS probands and family members of 59 Japanese nuclear
      families (223 members including 112 affected children). Forty-eight of these
      families had at least two affected children for which genome-wide linkage
      screening was carried out. The Genehunter software was used to perform
      nonparametric multipoint linkage analysis. Mutational and association analyses
      were conducted in all 59 Japanese FS families. RESULTS: Genotyping data of 407
      microsatellite markers suggested linkage of FSs to chromosome 18p11.2 (non
      parametric linkage score = 3.68, p = 0.0001). This region includes the IMPA2
      gene, which encodes myo-inositol monophosphatase (IMPase) 2. In the
      phosphatidylinositol-signaling pathway, IMPase is inhibited by lithium, which has
      a proconvulsant effect, and is stimulated by carbamazepine, an anticonvulsant. A
      systematic search was performed for mutations in IMPA2 in 24 unrelated randomly
      selected Japanese FS patients; seven variants were detected. Haplotype analysis
      revealed an association of a common haplotype in IMPA2 with FSs (p = 0.0009).
      CONCLUSION: The authors found a novel locus on chromosome 18p11.2 for febrile
      seizures (FSs). IMPA2 is likely to be an FS susceptibility gene.

PMID- 15557494
TI  - Epileptic seizures in systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the frequency and risk factors of epileptic seizures in a
      large cohort of patients with systemic lupus erythematosus (SLE). METHODS: Five
      hundred nineteen consecutive patients with SLE were studied, with follow-up
      ranging from 4 to 7.8 years. The type and frequency of risk factors associated
      with acute and recurrent epileptic seizures in SLE were determined. RESULTS:
      Sixty (11.6%) patients with epileptic seizures were identified. Epileptic
      seizures occurred at the onset of SLE symptoms in 19 (31.6%) and after the onset
      of SLE in 41 of 60 (68.3%) patients. Fifty-three of 60 (88.3%) patients had acute
      symptomatic epileptic seizures, and 7 of 60 (11.7%) had recurrent epileptic
      seizures. Variables associated with acute epileptic seizures at SLE onset were
      stroke (p = 0.0004) and antiphospholipid antibodies (p = 0.0013). Epileptic
      seizures during follow-up were related to nephritis (p = 0.001), antiphospholipid
      antibodies (p = 0.005), and epileptic seizures at disease onset (p = 0.00001).
      All seven patients who presented recurrent epileptic seizures had
      antiphospholipid syndrome and interictal epileptic abnormalities on EEG.
      CONCLUSIONS: Epileptic seizures were observed in 11.2% of systemic lupus
      erythematosus (SLE) patients. Antiphospholipid antibodies and stroke were related
      to epileptic seizures at SLE disease onset. Patients with renal flares, epileptic
      seizures at SLE disease onset, and antiphospholipid antibodies were at greater
      risk for acute symptomatic seizures during follow-up. Recurrence of epileptic
      seizures occurred in 1.3% of patients and was associated with antiphospholipid
      syndrome.

PMID- 15557495
TI  - Epileptic activity influences the lateralization of mesiotemporal fMRI activity.
AB  - OBJECTIVE: To identify clinical factors contributing to the lateralization of
      mesiotemporal memory functions in epilepsy by using memory-activated fMRI.
      METHODS: Sixty patients aged 16 to 63 years with mesial temporal lobe epilepsy
      (MTLE) and 20 patients aged 16 to 60 years with extratemporal epilepsy (ETE) due
      to circumscribed epileptogenic lesions who consecutively underwent presurgical
      evaluation including continuous video-EEG monitoring and structural MRI
      examinations were examined. During memory fMRI, the activation condition
      consisted of retrieval from long-term memory induced by self-paced performance of
      an imaginative walk through the patient's hometown. On the basis of a previous
      study, memory lateralization was defined as typical if larger fMRI activation was
      in the mesiotemporal structures contralateral to the epileptic focus. RESULTS:
      There were 45 patients with MTLE who had typical memory lateralization (75%),
      whereas only 9 patients (45%) with ETE exhibited typical memory lateralization (p
      = 0.013). In MTLE patients, bilateral independent epileptiform discharges
      occurred more often in the atypical group than in patients with typical memory
      lateralization (p = 0.015). CONCLUSIONS: The fMRI lateralization of mesiotemporal
      visuospatial memory functions in patients with mesiotemporal lobe epilepsy (MTLE)
      is asymmetric: The larger activation usually appears contralateral to the side of
      the epileptogenic region. These findings occur more often in MTLE; in patients
      with extratemporal epilepsy, such type of asymmetry is not characteristic. In
      MTLE patients with bilateral independent epileptiform discharges, this type of
      asymmetry is also less frequent.

PMID- 15557496
TI  - Cortical reorganization in malformations of cortical development: a
      magnetoencephalographic study.
AB  - BACKGROUND: The evaluation for epilepsy surgery of patients with malformations of
      cortical development (MCDs) in areas of clinically important cerebral function is
      a challenge because of the unpredictable localization of critical sensory, motor,
      and cognitive function. Magnetoencephalography (MEG) source localization of
      evoked fields can address whether functional reorganization of primary sensory
      modalities exists in MCDs. METHODS: Consecutive patients with MRI-demonstrated
      rolandic and calcarine cortex MCDs were identified who had a 148-channel whole
      head MEG study to identify the localization of primary somatosensory and visual
      cortices. Reorganization was considered when localization contrasted that
      expected upon general anatomic or homuncular rules and was defined against
      controls. RESULTS: Twelve patients (n = 12) were studied. Six had focal cortical
      dysplasia, two had polymicrogyria and schizencephaly, and four had isolated
      polymicrogyria. In the patients with cortical dysplasias, the somatosensory
      cortices were identified outside the rolandic area. In the two patients with
      polymicrogyria and schizencephaly, the somatosensory cortices remained in the
      rolandic areas as long as the anatomy was not distorted by the presence of the
      schizencephalic cleft. In the patients with isolated polymicrogyria, the
      somatosensory cortex was mapped without evidence of reorganization. CONCLUSION:
      In patients with epileptic MCDs involving rolandic and calcarine regions,
      cortical function may be reorganized if the MCDs are due to an abnormal neuronal
      or glial proliferation (i.e., cortical dysplasia) but may not be in MCDs caused
      by abnormal cortical organization (i.e., polymicrogyria).

PMID- 15557497
TI  - Reorganization of language-specific cortex in patients with lesions or mesial
      temporal epilepsy.
AB  - OBJECTIVE: To examine brain activation profiles for receptive language function,
      using magnetoencephalography (MEG), in patients with left hemisphere space
      occupying lesions and patients with left temporal lobe epilepsy due to mesial
      temporal sclerosis (MTS) and to evaluate whether cross- and intrahemispheric
      plasticity for language varied as a function of lesion type or location. METHODS:
      Twenty-one patients with MTS and 23 lesional patients underwent preoperative
      language mapping while performing a word recognition task. The anatomic location
      of late activity sources was determined by co-registering MEG coordinates onto
      structural MRI scans. A language laterality index was calculated based on the
      number of activity sources in each hemisphere. The location of language-specific
      activity was examined in relation to its proximity or overlap with Wernicke's
      area. RESULTS: A higher incidence of atypical language lateralization was noted
      among patients with MTS than lesional patients (43 vs 13%). The majority of MTS
      patients with early seizure onset (before age 5) showed atypical language
      lateralization. In contrast, the precise location of receptive language-specific
      cortex within the dominant hemisphere was found to be atypical (outside of
      Wernicke's area) in 30% of lesional patients and only 14% of MTS patients.
      CONCLUSIONS: There is an increased probability of a partial or total displacement
      of key components of the brain mechanism responsible for receptive language
      function to the nondominant hemisphere in mesial temporal sclerosis patients.
      Early onset of seizures is strongly associated with atypical language
      lateralization. Lesions in the dominant hemisphere tend to result in an
      intrahemispheric reorganization of linguistic function.

PMID- 15557498
TI  - Atypical language cortex in the left temporal lobe: relationship to bilateral
      language.
AB  - BACKGROUND: The intracarotid amobarbital procedure (IAP) is widely used in the
      preoperative evaluation for epilepsy surgery to lateralize language dominance and
      memory functions. However, language mapping has most often been accomplished with
      cortical brain stimulation. OBJECTIVE: To examine left temporal lobe language
      cortex representation using this technique in patients with bilateral language
      (BL) as compared with patients with left language dominance (LD). METHODS: The
      language maps of each patient were reviewed retrospectively. Group I consisted of
      10 patients with BL and Group II consisted of 10 matched control patients with
      LD. Each stimulation trial included a brief assessment of confrontation naming,
      automatic speech, reading, repetition, and comprehension. Clusters of errors that
      included comprehension, repetition, and naming defined primary temporal lobe
      language areas. RESULTS: Mapping revealed two distinct language areas in 60% of
      patients in Group I and 10% in Group II (p = 0.019). In Group I, two patients had
      both language areas in the same gyrus (either the superior or the middle temporal
      gyrus), whereas two showed one language area each in the superior and middle
      temporal gyri and the remaining two had one in the superior temporal gyrus and
      the other intermixed between the superior and middle temporal gyri. In Group II,
      both language areas were intermixed between the superior and middle temporal
      gyri. CONCLUSIONS: Bilateral language (BL) representation in the intracarotid
      amobarbital procedure is frequently associated with more than one noncontiguous
      language area in the left temporal lobe. A careful search for multiple language
      areas, particularly in patients with BL, is prudent prior to surgical resection.

PMID- 15557499
TI  - An fMRI study of cortical representation of mechanical allodynia in patients with
      neuropathic pain.
AB  - OBJECTIVE: To investigate cerebral activity associated with allodynia in patients
      with neuropathic pain. METHODS: The brain responses of 27 patients with
      peripheral (5), spinal (3), brainstem (4), thalamic (5), lenticular (5), or
      cortical (5) lesions were studied with fMRI as innocuous mechanical stimuli were
      addressed to either the allodynic territory or the homologous contralateral
      region. RESULTS: When applied to the normal side, brush and cold rubbing stimuli
      did not evoke pain and activated a somatosensory "control" network including
      contralateral primary (SI) and secondary (SII) somatosensory cortices and insular
      regions. The same stimuli became severely painful when applied to the allodynic
      side and activated regions in the contralateral hemisphere that mirrored the
      "control" network, with, however, lesser activation of the SII and insular
      cortices. Increased activation volumes were found in contralateral SI and primary
      motor cortex (MI). Whereas ipsilateral responses appeared very small and
      restricted after control stimuli, they represented the most salient effect of
      allodynia and were observed mainly in the ipsilateral parietal operculum (SII),
      SI, and insula. Allodynic stimuli also recruited additional responses in
      motor/premotor areas (MI, supplementary motor area), in regions involved in
      spatial attention (posterior parietal cortices), and in regions linking attention
      and motor control (mid-anterior cingulate cortex). CONCLUSION: On a background of
      deafferentation in the hemisphere contralateral to stimuli, enhanced or
      additional responses to innocuous stimuli in the ipsilateral hemisphere may
      contribute to the shift of perception from innocuous toward painful and ill
      defined sensations.

PMID- 15557500
TI  - Natural history of nonketotic hyperglycinemia in 65 patients.
AB  - BACKGROUND: Glycine encephalopathy, also known as nonketotic hyperglycinemia
      (NKH), is an autosomal recessive disorder caused by a defect in the glycine
      cleavage system. NKH is classically associated with neonatal apnea, lethargy,
      hypotonia, and seizures, followed by severe psychomotor retardation in those who
      survive. METHODS: To determine the natural history of NKH, the authors mailed a
      44-question survey to 170 households in the International NKH Family Network.
      RESULTS: Data for 65 patients (36 boys, 29 girls) were collected from 58
      families. One-third of the subjects died; 8 girls died during the neonatal
      period, and 14 patients died thereafter (2 girls, 12 boys). Median age of death
      for boys was 2.6 years vs <1 month for girls (p = 0.02). Mean birth weight and
      length, occipitofrontal circumference, and gestation duration were normal. Two
      thirds of infants were ventilated during the neonatal period; of these, 40% died.
      Ninety percent had confirmed seizures, 75% during the first month of life.
      Interestingly, three NKH patients never developed seizures. An abnormal corpus
      callosum and/or hydrocephalus were associated with especially poor gross motor
      and speech development. Of 25 patients living > or =3 years, 10 were able to walk
      and say/sign words; all were boys. In six families with more than one affected
      child, disease course and mortality were similar within each family. CONCLUSIONS:
      This study reveals a striking and unexpected gender difference in mortality and
      developmental progress. Of the two-thirds of nonketotic hyperglycinemia patients
      surviving the newborn period, up to 20% (mostly boys) may learn to walk and
      communicate by saying or signing words.

PMID- 15557501
TI  - Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.
AB  - OBJECTIVE: To clarify whether patients with clinical diagnoses of
      encephalitis/encephalopathy with a reversible lesion in the splenium of the
      corpus callosum (SCC) share common clinical features. METHODS: Possible
      encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI
      were collected retrospectively. Their clinical, laboratory, and radiologic data
      were reviewed. RESULTS: Fifteen encephalitis/encephalopathy patients with a
      reversible isolated SCC lesion were identified among 22 patients referred for
      this study. All 15 patients had relatively mild clinical courses. Twelve of the
      15 patients had disorders of consciousness. Eight patients had seizures, and
      three of them received antiepileptic drugs. All 15 patients clinically recovered
      completely within 1 month (8 patients within a week) after the onset of
      neurologic symptoms. The SCC lesion was ovoid in six patients; it extended
      irregularly from the center to the lateral portion of SCC in the other eight
      patients. Homogeneously reduced diffusion was seen in all seven patients who
      underwent diffusion-weighted imaging. There was no enhancement in the five
      patients so examined. The SCC lesion had completely disappeared in all patients
      at follow-up MRI exams between 3 days and 2 months after the initial MRI (within
      1 week in eight patients). CONCLUSION: The clinical features among the affected
      patients were nearly identical, consisting of relatively mild CNS manifestations
      and complete recovery within 1 month.

PMID- 15557502
TI  - Temporal bone histopathology in dominantly inherited audiovestibular syndrome.
AB  - OBJECTIVE: To describe the clinical and pathologic features of a new dominantly
      inherited audiovestibular syndrome. METHODS: History, examination, and
      audiometric testing in the proband, brother, and son; quantitative rotational
      testing in the proband and son; histopathology of the cochlea and vestibular
      labyrinth in the proband; sequencing candidate genes COCH and MYO7A in the
      brother and son. RESULTS: Affected family members developed slowly progressive
      hearing loss beginning in their late 30s and progressive imbalance in their early
      70s. Three of four affected had brief (minutes) episodes of vertigo typically
      occurring a few times per year. Auditory and vestibular function testing
      documented a slowly progressive loss of auditory and vestibular function.
      Postmortem examination showed a loss of hair cells in the cochlea and vestibular
      receptor organs. There were no cellular infiltrates or acidophilic deposits. No
      mutations were found in the COCH or MYO7A genes. CONCLUSIONS: This dominantly
      inherited audiovestibular syndrome results in a selective loss of hair cells in
      the auditory and vestibular end organs. Finding the causative gene could have
      important implications for understanding the pathophysiology of presbycusis and
      dysequilibrium of aging.

PMID- 15557503
TI  - The effect of tactile feedback on pantomime of tool use in apraxia.
AB  - OBJECTIVE: To investigate whether apraxic patients' better performance with real
      tools compared to miming is due to the tactile feedback provided by holding the
      tool. METHODS: Ten patients with aphasia and apraxia from left hemisphere damage
      were asked to demonstrate the use of 12 tools and objects under three conditions:
      miming with empty hands, miming with an implement shaped like the handle of the
      tool, and using the real tool with its corresponding object. RESULTS: Whereas
      real tool use was much better than pantomime in all patients, tactile feedback
      from the isolated handle facilitated miming only in some and deteriorated it in
      others so that across the group there was no significant improvement.
      CONCLUSIONS: The better performance of real than of pretended tool use does not
      depend on tactile feedback per se, but on the mechanical affordances and
      constraints of tools and objects transmitted by this feedback in real use.
      Tactile feedback deprived of these contents and restricted to the shape of the
      handle does not substantially help produce the appropriate action.

PMID- 15557504
TI  - Association of cholesterol with stroke risk varies in stroke subtypes and patient
      subgroups.
AB  - OBJECTIVE: To perform a health maintenance organization-based case-control study
      to evaluate the association of total and high density lipoprotein (HDL)
      cholesterol with the risk of stroke subtypes and in patient subgroups. METHODS:
      Cases had a confirmed incident ischemic stroke (n = 1,242) or hemorrhagic stroke
      (n = 313). Controls (n = 6,455) were identified in a companion myocardial
      infarction study. Risk of stroke was modeled using logistic regression. RESULTS:
      The highest total cholesterol quintile was associated with an increased risk of
      ischemic stroke compared to the lowest quintile (OR = 1.6, 95% CI 1.3 to 2.0)
      with the strongest subtype associations for atherosclerotic stroke (OR = 3.2) and
      lacunar stroke (OR = 2.4). The highest HDL cholesterol quintile was associated
      with a decreased risk of ischemic stroke compared to the lowest quintile (OR =
      0.8, CI 0.6 to 1.0). Subgroup analyses suggested that the total cholesterol
      association was more important for patients < 66 years of age and those with HDL
      < 50 mg/dL; the HDL association was more important for patients without diabetes
      or atrial fibrillation. The second through fourth total cholesterol quintiles
      were associated with a decreased risk of hemorrhagic stroke compared to the
      lowest quintile (OR = 0.7, CI 0.5 to 1.0). CONCLUSIONS: Higher total and lower
      HDL cholesterol levels were associated with increased risk of ischemic stroke,
      especially certain stroke subtypes and patient subgroups. The lowest levels of
      total cholesterol were associated with an increased risk of all hemorrhagic
      strokes.

PMID- 15557505
TI  - A 24-year follow-up of body mass index and cerebral atrophy.
AB  - OBJECTIVE: To investigate the longitudinal relationship between body mass index
      (BMI), a major vascular risk factor, and cerebral atrophy, a marker of
      neurodegeneration, in a population-based sample of middle-aged women. METHODS: A
      representative sample of 290 women born in 1908, 1914, 1918, and 1922 was
      examined in 1968 to 1969, 1974 to 1975, 1980 to 1981, and 1992 to 1993 as part of
      the Population Study of Women in Goteborg, Sweden. At each examination, women
      completed a survey on a variety of health and lifestyle factors and underwent
      anthropometric, clinical, and neuropsychiatric assessments and blood collection.
      Atrophy of the temporal, frontal, occipital, and parietal lobes was measured on
      CT in 1992 when participants were age 70 to 84. Univariate and multivariate
      regression analyses were used to assess the relationship between BMI and brain
      measures. RESULTS: Women with atrophy of the temporal lobe were, on average, 1.1
      to 1.5 kg/m2 higher in BMI at all examinations than women without temporal
      atrophy (p < 0.05). Multivariate analyses showed that age and BMI were the only
      significant predictors of temporal atrophy. Risk of temporal atrophy increased 13
      to 16% per 1.0-kg/m2 increase in BMI (p < 0.05). There were no associations
      between BMI and atrophy measured at three other brain locations. CONCLUSION:
      Overweight and obesity throughout adult life may contribute to the development of
      temporal atrophy in women.

PMID- 15557506
TI  - Vascular risk factors, incidence of MCI, and rates of progression to dementia.
AB  - OBJECTIVE: To estimate prevalence, incidence, and rate of progression of mild
      cognitive impairment (MCI) to dementia and correlated vascular risk factors with
      incident MCI and its progression to dementia. METHODS: The authors evaluated
      2,963 individuals from the population-based sample of 5,632 subjects 65 to 84
      years old, at the first (1992 to 1993) and second survey (1995 to 1996) of the
      Italian Longitudinal Study on Aging (ILSA), with a 3.5-year follow-up. Dementia,
      Alzheimer disease (AD), vascular dementia (VaD), other types of dementia, and MCI
      were classified using current clinical criteria. RESULTS: Among the 2,963
      participants, 139 MCI patients were diagnosed at the first ILSA survey. During
      the 3.5-year follow-up, 113 new events of MCI were diagnosed with an estimated
      incidence rate of 21.5 per 1,000 person-years. We found a progression rate to
      dementia (all causes) of 3.8/100 person-years. Specific progression rates for AD,
      VaD, and other types of dementia were 2.3, 1.3, and 0.3/100 person-years.
      Furthermore, age was a risk factor for incident MCI (RR: 5.93, 95% CI: 3.17 to
      11.10), while education was protective (RR: 0.06, 95% CI: 0.03 to 0.10), and
      serum total cholesterol evidenced a borderline nonsignificant trend for a
      protective effect. There was a nonsignificant trend for stroke as a risk factor
      of progression of MCI to dementia. CONCLUSIONS: In this population, among those
      who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk
      factors influence incident mild cognitive impairment and the rate of progression
      to dementia.

PMID- 15557507
TI  - Hippocampal atrophy, whole brain volume, and white matter lesions in older
      hypertensive subjects.
AB  - OBJECTIVE: To determine the potential role of whole brain atrophy, hippocampal
      atrophy, or both, and small vessel disease/white matter lesions as mechanisms
      underlying the cognitive impairment associated with hypertension. METHODS: Using
      MRI scanning the authors determined hippocampal volumes, whole brain volumes, and
      location and severity of white matter lesions, using Scheltens scale, in 103
      hypertensive (166 +/- 8/88 +/- 7 mm Hg, 54 female) and 51 normotensive (132 +/-
      12/74 +/- 7 mm Hg, 21 female) subjects age > or = 70 years. RESULTS: Compared to
      normotensive subjects, older hypertensive subjects had significantly smaller
      whole brain volumes (887 +/- 109 vs 930 +/- 97 cm3, p = 0.02) and
      nonsignificantly reduced hippocampal volumes (5.39 +/- 1.60 vs 5.67 +/- 1.80 cm3,
      p = 0.33). Hypertensive subjects had an increased burden of periventricular
      lesions: bands (p = 0.03), frontal caps (p = 0.08), occipital caps (p = 0.07),
      and total periventricular hyperintensities (p = 0.02). They also had higher
      scores in subcortical areas: frontal (p = 0.04), temporal (p = 0.03), and deep
      white matter areas (p = 0.05). A correlation was found between whole brain
      volumes and systolic blood pressure (r = -0.19, p = 0.02). No correlation was
      seen between whole brain volumes and white matter lesion burden. CONCLUSIONS:
      Moderate hypertension in non-impaired older subjects is associated with smaller
      whole brain volume and an increased burden of subcortical and periventricular
      white matter lesions.

PMID- 15557508
TI  - Impact of APOE in mild cognitive impairment.
AB  - OBJECTIVE: The authors aimed to use baseline data of an ongoing large,
      prospective study in subjects with mild cognitive impairment (MCI) to investigate
      the impact of APOE genotype on the symptom profile of the condition. METHODS:
      Cognitive assessments included the AD Assessment Scale cognitive subscale (ADAS
      cog), the Mini-Mental State Examination (MMSE), and a cognitive battery for
      assessment of memory, attention, and executive function. Behavioral assessments
      included the Neuropsychiatric Inventory and Beck Depression Inventory. Activities
      of daily living were assessed by the AD Cooperative Study Activities of Daily
      Living (ADCS-ADL) scale. Hippocampal volumes were measured with MRI. RESULTS: A
      total of 494 of 1,018 study subjects provided APOE data. Approximately 40% of the
      subjects were APOE epsilon4 carriers. APOE epsilon4 carriers had lower MMSE (p =
      0.01) and higher ADAS-cog (p < 0.0001) scores than noncarriers, indicating worse
      cognitive impairment. APOE epsilon4 carriers also had greater deficits on New
      York University delayed paragraph recall and Buschke free and cued selective
      reminding tests, and on the ADCS-ADL scale (p < 0.001). They also had smaller
      hippocampal volumes (p = 0.002). Behavioral scores were similar across the
      subgroups. CONCLUSION: MCI subjects carrying the APOE epsilon4 allele showed
      distinct cognitive and imaging profiles, which appeared to resemble those of
      early Alzheimer patients. APOE epsilon4 genotype was associated with greater
      impairments in memory and functional activities as well as hippocampal atrophy.

PMID- 15557509
TI  - Diabetes mellitus in midlife and the risk of dementia three decades later.
AB  - OBJECTIVE: To examine the association between diabetes in midlife (1963-1968) and
      dementia more than three decades later (1999-2001). METHODS: The authors
      characterized dementia using standard methods for 1,892 participants among 2,606
      survivors of 10,059 participants in the Israeli Ischemic Heart Disease study, a
      longitudinal investigation of the incidence of and risk factors for
      cardiovascular disease among Jewish male civil servants in Israel. Face to face
      interviews were conducted with the 652 subjects identified as possibly demented
      by the Modified Telephone Interview for Cognitive Status. Logistic regression
      analysis was performed to assess the association of diabetes with dementia
      controlling for sociodemographic and cardiovascular variables compared to those
      with no cognitive impairment. RESULTS: Of 1,892 assessed subjects (mean age 82 at
      assessment), 309 (16.3%) had dementia. Diabetic subjects had significantly more
      dementia than non-diabetic subjects (chi2 = 7.54, df = 1, p = 0.006, OR 2.83 [95%
      CI = 1.40 to 5.71]). Those who survived to the time of this study were younger
      and healthier than those who died. CONCLUSIONS: Evidence for diabetes as a risk
      factor for dementia was found, similar to other epidemiologic studies. In
      contrast to the earlier studies, however, the authors linked diabetes in midlife
      to dementia more than three decades later in the very old survivors of a large
      male cohort.

PMID- 15557510
TI  - Is fatigue an independent and persistent symptom in patients with Parkinson
      disease?
AB  - OBJECTIVE: To evaluate if mental fatigue is a symptom that appears independently
      from other clinical features in patients with Parkinson disease (PD), and to
      study if fatigue is persistent over time in these patients. METHODS: In 1993, 233
      patients with PD were included in a community-based study of fatigue and followed
      prospectively over 8 years. Fatigue was measured by a combination of a seven
      point scale and parts of the Nottingham Health Profile (NHP) at baseline and
      after 4 and 8 years. In addition, the Fatigue Severity Scale (FSS) was used to
      evaluate fatigue in 2001. Population-averaged logistic regression models for
      correlated data were performed to study the relationship between fatigue and
      various demographic and clinical variables. RESULTS: In patients who were
      followed throughout the 8-year study period, fatigue increased from 35.7% in 1993
      to 42.9% in 1997 and 55.7% in 2001. Fatigue was related to disease progression,
      depression, and excessive daytime sleepiness (EDS). However, the prevalence of
      fatigue in patients without depression and EDS remained high and increased from
      32.1% to 38.9% during the study period. For about 44% of the patients with
      fatigue the presence of this symptom varied during the study period, as it was
      persistent in 56% of the patients with fatigue. CONCLUSIONS: The authors
      confirmed the high prevalence of mental fatigue in patients with Parkinson
      disease (PD). Fatigue is related to other non-motor features such as depression
      and excessive daytime sleepiness, but cannot be explained by this comorbidity
      alone. In more than half of the patients mental fatigue is persistent and seems
      to be an independent symptom that develops parallel to the progressive
      neurodegenerative disorder of PD.

PMID- 15557511
TI  - Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson
      disease.
AB  - BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels
      of the substantia nigra (SN) in patients with Parkinson disease (PD) and in
      control subjects. It is not known whether iron accumulation in PD is a primary or
      secondary phenomenon. However, sequence variations in genes involved in iron
      metabolism have been linked to basal ganglia disorders. One of these is
      ceruloplasmin (Cp), which is vitally involved in iron transport across the cell
      membrane. METHODS: One hundred seventy-six patients with PD according to the UK
      Brain Bank criteria and 180 ethnically matched control subjects, who were
      previously examined for SN iron signal changes by transcranial ultrasound, were
      examined for mutations in the Cp gene using denaturing high-performance liquid
      chromatography and subsequent sequencing for verification of unequivocal signals.
      Immunohistochemistry of PD midbrains was performed to examine the presence of Cp
      in Lewy bodies. RESULTS: Five novel missense variations were detected. One of
      these (I63T) was found in a single PD patient. A known variation (D554E) was
      significantly associated with PD and the ultrasound marker for increased SN iron
      levels. Moreover, a third sequence variation (R793H) was found to segregate with
      the ultrasound marker for increased iron levels in patients and control subjects.
      Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD.
      CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD)
      patient or associated with the ultrasound marker for increased substantia nigra
      iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy
      bodies underline a suspected role for Cp in the pathogenesis of PD. Further
      functional analyses are warranted to investigate whether these variations are
      causally linked to the complex pathogenesis of PD in a subset of cases.

PMID- 15557512
TI  - Neuro-ophthalmology of late-onset Tay-Sachs disease (LOTS).
AB  - BACKGROUND: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal
      recessive, progressive variant of GM2 gangliosidosis, characterized by
      involvement of the cerebellum and anterior horn cells. OBJECTIVE: To determine
      the range of visual and ocular motor abnormalities in LOTS, as a prelude to
      evaluating the effectiveness of novel therapies. METHODS: Fourteen patients with
      biochemically confirmed LOTS (8 men; age range 24 to 53 years; disease duration 5
      to 30 years) and 10 age-matched control subjects were studied. Snellen visual
      acuity, contrast sensitivity, color vision, stereopsis, and visual fields were
      measured, and optic fundi were photographed. Horizontal and vertical eye
      movements (search coil) were recorded, and saccades, pursuit, vestibulo-ocular
      reflex (VOR), vergence, and optokinetic (OK) responses were measured. RESULTS:
      All patients showed normal visual functions and optic fundi. The main eye
      movement abnormality concerned saccades, which were "multistep," consisting of a
      series of small saccades and larger movements that showed transient
      decelerations. Larger saccades ended earlier and more abruptly (greater peak
      deceleration) in LOTS patients than in control subjects; these changes can be
      attributed to premature termination of the saccadic pulse. Smooth-pursuit and
      slow-phase OK gains were reduced, but VOR, vergence, and gaze holding were
      normal. CONCLUSIONS: Patients with late-onset Tay-Sachs disease (LOTS) show
      characteristic abnormalities of saccades but normal afferent visual systems.
      Hypometria, transient decelerations, and premature termination of saccades
      suggest disruption of a "latch circuit" that normally inhibits pontine omnipause
      neurons, permitting burst neurons to discharge until the eye movement is
      completed. These measurable abnormalities of saccades provide a means to evaluate
      the effects of novel treatments for LOTS.

PMID- 15557513
TI  - A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild
      mental retardation.
AB  - BACKGROUND: Identifying the genetic factors that contribute to memory and
      learning is limited by the complexity of brain development and the lack of
      suitable human models for mild disorders of cognition. METHODS: Previously, a
      disease locus was mapped for a mild type of nonsyndromic mental retardation (IQ
      between 50 and 70) to a 4.2-MB interval on chromosome 3p25-pter in a large
      kindred. The genes and transcripts within the candidate region were
      systematically analyzed for mutations by single-strand polymorphism analysis and
      DNA sequencing. RESULTS: A nonsense mutation causing a premature stop codon in a
      novel gene (cereblon; CRBN) was identified that encodes for an ATP-dependent Lon
      protease. The predicted protein sequence is highly conserved across species, and
      it belongs to a family of proteins that selectively degrade short-lived
      polypeptides and regulate mitochondrial replication and transcription. One member
      of the Lon-containing protein family is regionally expressed in the human
      hippocampus, an important neuroanatomic region that is involved in long-term
      potentiation and learning. The mutation in the CRBN gene described interrupts an
      N-myristoylation site and eliminates a casein kinase II phosphorylation site at
      the C terminus. CONCLUSIONS: A gene on chromosome 3p that is associated with mild
      mental retardation in a large kindred is reported. This finding implicates a role
      for the ATP-dependent degradation of proteins in memory and learning.

PMID- 15557514
TI  - Transient crossed aphasia during focal right-hemisphere seizure.

PMID- 15557515
TI  - Functional outcome measures as clinical trial endpoints in ALS.
AB  - The topiramate study was a 12-month randomized placebo-controlled trial in
      patients with ALS. Follow-up evaluation of the placebo group (n = 97) constituted
      a well-described cohort of patients with ALS, in whom multiple outcome measures
      were assessed at 3-month intervals. During the 12-month study period, the decline
      of forced vital capacity (FVC%) and ALS functional rating scale (ALSFRS) was
      linear, whereas the decline of maximum voluntary isometric contraction-arm (MVIC
      arm) and MVIC-grip Z scores was curvilinear. Rates of FVC% and ALFRS decline, but
      not of MVIC-arm or MVIC-grip, were independent predictors of survival.

PMID- 15557516
TI  - A novel candidate region for ALS on chromosome 14q11.2.
AB  - Sequence variations with biologic effect in ALS have been identified in the gene
      for vascular endothelial growth factor (VEGF). The gene for a related protein,
      angiogenin, lies on chromosome 14q11.2. Analysis of the angiogenin (ANG) gene in
      the authors' population has demonstrated a significant allelic association with
      the rs11701 single nucleotide polymorphism (SNP) and identified a novel mutation
      in two individuals with sporadic ALS that potentially inhibits angiogenin
      function. These observations propose a candidate region for ALS on chromosome
      14q11.2 and suggest that other genes with similar function to VEGF may be
      important in the pathogenesis of ALS.

PMID- 15557517
TI  - Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1.
AB  - Cardiac tachyarrhythmias have rarely been studied in young patients with myotonic
      dystrophy type 1 (DM1). The authors observed major cardiac rhythm disturbances in
      11 patients aged 10 to 18 years. Tachyarrhythmic events were more frequent than
      impulse conduction disorders. Wide variations in CTG expansion were observed
      among the population. Since physical exercise was a prominent arrhythmogenic
      factor, systematic exercise tests with EKG monitoring may be indicated in young
      patients with DM1.

PMID- 15557518
TI  - Single-fiber EMG in familial hemiplegic migraine.
AB  - Twelve familial hemiplegic migraine (FHM) patients (6 with the I1811L mutation in
      CACNA1A, 3 with M731T mutation in ATP1A2, and 3 without known mutations) and 10
      control subjects underwent single-fiber EMG. Mean jitter did not differ
      significantly between patients and control subjects or among patients. No
      blocking was found. The results suggest that neuromuscular function is normal in
      FHM.

PMID- 15557519
TI  - Late-onset optic pathway tumors in children with neurofibromatosis 1.
AB  - Identification of new optic pathway tumors (OPTs) and progression of pre-existing
      OPTs in children with neurofibromatosis 1 (NF1) have been reported infrequently
      after age 6. The authors present eight children with NF1 (mean age 12.2 years)
      seen in three NF1 centers who had either late-onset (four of eight) or late
      progressive (seven of eight) OPT. Continued monitoring of individuals with NF1
      into adulthood for the development of OPTs and for progression of known OPTs is
      warranted.

PMID- 15557520
TI  - Value of Hu antibody determinations in the follow-up of paraneoplastic neurologic
      syndromes.
AB  - The long-term evolution of Hu antibody (Hu-Ab) titers in patients with
      paraneoplastic neurologic syndromes (PNSs) is not known. Described is the
      evolution of Hu-Ab titers in 35 patients with PNS with a median follow-up of 32
      months (range 6 to 108 months). No correlation was observed between Hu-Ab titers
      and neurologic outcome, tumor evolution, or type of treatment. Serial Hu-Ab
      determinations are not useful for monitoring the clinical outcome of patients
      with PNS.

PMID- 15557521
TI  - Early epidural blood patch in spontaneous intracranial hypotension.
AB  - Thirty patients with a typical orthostatic headache were treated by early lumbar
      epidural blood patch (EBP) without previously performing lumbar puncture or
      identifying a CSF leak and with or without typical MRI changes. A complete cure
      was obtained in 77% of patients after one (57%) or two (20%) EBPs. Spontaneous
      intracranial hypotension with typical orthostatic headache can be diagnosed
      without lumbar puncture and can be cured by early EBP in a majority of patients.

PMID- 15557522
TI  - Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age
      70 years.
AB  - The effects of subthalamic nucleus deep brain stimulation were studied in 52
      consecutive patients (13 over age 70, 15 under age 60, 24 age 60 to 70). All
      groups had improvement of motor fluctuations and dyskinesia. Patients over age 70
      had worsening of Unified Parkinson's Disease Rating Scale motor scores on
      medication, despite less medication reduction. Their activities of daily living
      and axial subscores worsened, particularly in those with preoperative gait
      difficulties.

PMID- 15557523
TI  - Standardized protocols increase organ and tissue donation rates in the
      neurocritical care unit.
AB  - The authors tested the effect of uncoupling and removal of the treating physician
      from organ and tissue donation requests on consent rates for donation in the
      neurocritical care unit. After a neurointensivist-led policy change, consent
      rates increased from 23.1 to 36.5% (odds ratio = 1.9, p = 0.01), whereas there
      was no change in other hospital units. This supports such a policy change and
      shows a positive effect of a neurointensivist on organ and tissue procurement.

PMID- 15557524
TI  - Sirolimus may not cause neurotoxicity in kidney and liver transplant recipients.
AB  - Neurotoxicity associated with calcineurin inhibitors cyclosporin A and tacrolimus
      is established. Sirolimus is a new agent related to tacrolimus, but its mechanism
      of action differs. The authors reviewed 202 transplant recipients treated with
      sirolimus from 2001 to 2004. They found no evidence of neurotoxicity with
      sirolimus therapy for up to 18 months (range, 15 days to 3 years). Sirolimus
      could be considered a substitute immunosuppressant for patients with cyclosporin
      A or tacrolimus neurotoxicity.

PMID- 15557525
TI  - Memory complaints in nondemented men predict future pathologic diagnosis of
      Alzheimer disease.
AB  - The validity of memory complaints as a predictor of Alzheimer disease (AD) was
      assessed in 237 Japanese-American men autopsied at ages 74 to 97 years. These men
      were free of dementia at the time memory complaints were assessed 1 to 11 years
      earlier. Memory complaints were found to predict the neuropathologic diagnosis of
      AD after adjusting for age, time to death, education, depression, and cognitive
      functioning.

PMID- 15557526
TI  - Progressive prosopagnosia: clinical and neuroimaging results.
AB  - The authors report the longitudinal case study of a patient with the right
      temporal variant of frontotemporal lobar degeneration. His deficit, initially
      limited to visuoperceptual disturbances, progressed 2 years later to a severe
      semantic breakdown. Neuroimaging data indicate that the underlying degenerative
      process, initially confined to unimodal visual associative cortices, progressed
      along the ventral pathways to multimodal areas in charge of integrating knowledge
      from various modalities (the anterior temporal lobes).

PMID- 15557527
TI  - CSF characteristics in early-onset multiple sclerosis.
AB  - The authors studied CSF characteristics in 136 patients with multiple sclerosis
      (MS) with a disease onset before age 16. In the initial diagnostic lumbar
      puncture, CSF-pleocytosis was observed in 66%, blood-CSF barrier dysfunction in
      13%, and oligoclonal IgG in 92% of the early-onset MS (EOMS) patients. CSF
      oligoclonal IgG supports the early diagnosis of MS in childhood with a
      sensitivity similar to adult-onset MS.

PMID- 15557528
TI  - Early-onset encephalopathy and cortical myoclonus in a boy with MECP2 gene
      mutation.
AB  - The authors report the unusual clinical and neurophysiologic features of a
      sporadic case of a boy carrying an 806delG mutation on the MECP2 gene. A 28-month
      old boy was examined for severe developmental delay, seizures, microcephaly,
      breathing dysfunction, and spontaneous and evoked myoclonic jerks of upper limbs.
      Neurophysiologic study proved the cortical origin of myoclonus; however, it was
      not associated with signs of cortical hyperexcitability. 3-Methoxy-4-hydroxy
      phenylethylene glycol and valine concentrations were low in CSF.

PMID- 15557529
TI  - Repeated dosing of botulinum toxin type A for upper limb spasticity following
      stroke.
AB  - The authors evaluated the long-term efficacy and safety of botulinum toxin type A
      (BTX-A) in poststroke spasticity patients who completed a 12-week placebo
      controlled study and received multiple open-label treatments with 200 to 240 U
      BTX-A for 42 weeks. Significant and sustained improvements were observed for
      Disability Assessment and Ashworth scores. Adverse events were generally mild.
      This extension of a double-blind study demonstrates that repeated treatments of
      BTX-A significantly improve function and tone in spasticity.

PMID- 15557530
TI  - Stroke in rural Ecuador: a three-phase, door-to-door survey.
AB  - The authors carried out a three-phase door-to-door survey in Atahualpa, Ecuador
      to assess epidemiologic and pathogenetic mechanisms of stroke. They found 10
      stroke patients among 1,568 individuals aged > or =15 years (crude prevalence,
      638 per 100,000). There was only one incident case (incidence, 64 per 100,000).
      Six of the 10 patients had hypertensive arteriolopathy (five with ischemic and
      one with hemorrhagic stroke). Additional work is needed to increase knowledge on
      stroke in developing countries.

PMID- 15557531
TI  - Recurrent longitudinal myelitis as primary manifestation of SLE.

PMID- 15557532
TI  - SCN4A-associated hypokalemic periodic paralysis merits a trial of acetazolamide.

PMID- 15557533
TI  - Creutzfeldt-Jakob disease with a novel insertion and codon 219 Lys/Lys
      polymorphism in PRNP.

PMID- 15557534
TI  - No CCM2 mutations in a cohort of 31 sporadic cases.

PMID- 15557535
TI  - Preferential gray matter involvement in dengue myelitis.

PMID- 15557536
TI  - Acquired hepatocerebral degeneration without overt liver disease.

PMID- 15557537
TI  - Strokelike presentation of Wilson disease with homozygosity for a novel T766R
      mutation.

PMID- 15557538
TI  - Frequency-specific mal de debarquement.

PMID- 15557539
TI  - Aortic occlusion causing ischemic neuropathy and paraparesis.

PMID- 15557540
TI  - Practice parameter: diagnostic assessment of the child with cerebral palsy:
      report of the Quality Standards Subcommittee of the American Academy of Neurology
      and the Practice Committee of the Child Neurology Society.

PMID- 15557541
TI  - Anti-GQ1b antibody as a factor predictive of mechanical ventilation in Guillain
      Barre syndrome.

PMID- 15557542
TI  - Excess incidence of ALS in young Gulf War veterans.

PMID- 15557543
TI  - Does magnetoencephalography add to scalp video-EEG as a diagnostic tool in
      epilepsy surgery?

PMID- 15557544
TI  - Objective tests for upper motor neuron involvement in amyotrophic lateral
      sclerosis (ALS).

PMID- 15557545
TI  - Initial individualized selection of long-term anticonvulsant drugs by
      neurologists.

PMID- 15557546
TI  - Reproductive health effects and teratogenicity of antiepileptic drugs.
AB  - Women with epilepsy are less likely to bear children than women in the general
      population, and although this reduced fertility can be attributed in part to
      effects of the disease itself, the effects of antiepileptic drugs (AEDs),
      including changes in reproductive endocrine function, are also a factor.
      Conversely, some AEDs interact with oral contraceptives and can increase the risk
      for contraceptive failure and unplanned pregnancy. Women with epilepsy also have
      elevated rates of congenital anomalies and major malformations in their
      offspring, for which exposure of the developing fetus to AEDs taken by the mother
      appears to be responsible. In utero exposure to some AEDs may also be associated
      with increased risk for impaired cognitive function in the growing child.
      Clearly, possible long-term effects on reproductive health and pregnancy outcomes
      require careful attention when AED therapy is being considered for a patient with
      childbearing potential. Moreover, because AEDs are increasingly being used in
      therapy for other conditions such as migraine, bipolar disorder, and pain, it is
      not only the treatment of women with epilepsy that will be affected by these
      concerns.

PMID- 15557547
TI  - Metabolic concerns associated with antiepileptic medications.
AB  - Because treatment with antiepileptic drugs (AEDs) is often for years or lifelong,
      physicians should be aware of the metabolic changes that can be associated with
      AED use and the potential effects of these changes during long-term therapy.
      Alterations of bone metabolism leading to decreased bone mineral density,
      associated particularly but not exclusively with the hepatic enzyme-inducing
      AEDs, can worsen the risk for fractures, which is already increased in patients
      with epilepsy by factors such as seizure-related falls and trauma. Some AEDs are
      associated with weight gain, an effect that is not only distressing to many
      patients but may be sufficient to increase the risk for cardiovascular disease
      and other disorders associated with excessive body weight. The carbonic anhydrase
      inhibiting properties of some AEDs can lead to metabolic acidosis. The AEDs that
      inhibit carbonic anhydrase are also associated with an increase in risk for renal
      stones, as is the ketogenic diet. Awareness of the potential metabolic
      disturbances associated with AED use is particularly important because many of
      them are subtle and may take years to become clinically apparent.

PMID- 15557548
TI  - Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic
      drugs.
AB  - One of the major differences between the older antiepileptic drugs (AEDs) and the
      newer AEDs is the potential of the older AEDs for significant interactions with
      other medications. Many of the drug-drug interactions involving the older AEDs
      are reciprocal, i.e., both drugs affect each other. In contrast, the newer AEDs
      have either no or limited drug interaction potential. Despite our extensive
      understanding of and our ability to predict drug-drug interactions, serious drug
      interactions still occur. More than 30% of all new seizures occur in the elderly,
      and because this population may be taking a variety of other medications the
      addition of an AED can have profound impact on these other therapies. In women,
      the use of enzyme-inducing AEDs can cause significant alterations of sex hormones
      and can decrease the efficacy of oral contraceptives. In children and adults, the
      use of enzyme inducers may result in long-term endocrine effects, including bone
      loss and lipid, thyroid, and sex hormone abnormalities. Phenytoin and
      phenobarbital are metabolized by cytochrome P450 isozymes, with activity
      dependent on genetic polymorphism (CYP2C9, CYP2C19). The dosing of the newer AEDs
      is not affected by genetic polymorphism. The decreased induction and inhibition
      effects and the lack of significant genetic polymorphism of the newer AEDs allow
      increased ease of use and perhaps greater safety, especially for patients taking
      multiple medications.

PMID- 15557549
TI  - Initial treatment of epilepsy with antiepileptic drugs: pediatric issues.
AB  - The selection of an antiepileptic drug (AED) for initial treatment of epilepsy in
      infancy, childhood, and adolescence should ideally be made after a clear
      syndromic diagnosis of the patient's seizure disorder. A common cause of failure
      of the first AED is erroneous diagnosis. The availability of new-generation AEDs
      has expanded the choice of available agents with comparable efficacy for most
      syndromes. Efficacy data based on class I or II evidence are not available for
      many syndromes of childhood, and selection must therefore be based on the best
      data available. It is also important to assess the relative toxicity and
      tolerability of AEDs in making the selection. It is especially important to
      appreciate age-specific organ toxicities. Moreover, the use of AEDs in childhood
      requires an understanding of their neurobehavioral effects. Important
      neuropsychiatric co-morbidities in children with epilepsy include attention
      deficit/hyperactivity disorder, autistic spectrum disorders, depression and
      anxiety, and thought disorders. These problems can be exacerbated or ameliorated
      by specific AEDs. The effect of AEDs on body weight, insulin sensitivity, lipid
      profile, and bone health is becoming better appreciated. Newer AEDs may offer
      significant advantages in this regard. Co-morbid migraine in children with
      epilepsy may benefit from some AEDs. There remains a continuing need for the
      development of newer AEDs that are targeted for the developing brain to improve
      the efficacy and tolerability of treatment in childhood seizure disorders.

PMID- 15557550
TI  - Initial treatment of epilepsy: special issues in treating the elderly.
AB  - The incidence of new-onset epilepsy is higher among the elderly, the most rapidly
      growing segment of the population, than in any other age group. New-onset
      seizures in elderly patients are typically cryptogenic or symptomatic partial
      seizures that require long-term treatment. Because seizures in the elderly are
      often readily controlled, considerations of tolerability and safety, including
      pharmacokinetics and the potential for drug interactions, may be as important as
      efficacy in the selection of an antiepileptic drug (AED). The newer AEDs
      introduced during the past decade offer advantages in this respect over older
      agents. Phenytoin is the most widely used AED in the United States, but its
      hepatic metabolism and associated enzyme induction, as well as its nonlinear
      pharmacokinetics, are particular disadvantages for elderly patients. Because of
      their potential effects on cognitive function, sedating AEDs such as
      phenobarbital and primidone have little place in the treatment of new-onset
      seizures in elderly patients. Carbamazepine also is an enzyme-inducing agent with
      significant potential for drug interactions. Among the newer AEDs, gabapentin and
      levetiracetam have good safety and cognitive effect profiles and do not interact
      with other drugs, and lamotrigine offers many of the same benefits. Oxcarbazepine
      has better tolerability than carbamazepine, and topiramate and zonisamide,
      although they have more cognitive side effects than the other new AEDs, can be
      considered for some elderly patients. Forthcoming data from the Veterans Affairs
      Cooperative Trial 428, as well as recent guidelines from the American Academy of
      Neurology and the American Epilepsy Society, are likely to provide support for
      the use of selected second-generation AEDs as first-line agents for the treatment
      of epilepsy in elderly patients.

PMID- 15557551
TI  - Tolerability of antiseizure medications: implications for health outcomes.
AB  - Epilepsy is a disorder of abnormal excitability and synchronicity of aggregates
      of neurons that lead to paroxysmal behavioral or perceptual change. Most
      antiepileptic drugs (AEDs) decrease membrane excitability or increase
      postsynaptic inhibition, and may alter synchronization of neuronal networks. The
      attributes of an AED that reduce the tendency toward seizures may cause
      disruption of normal cerebral processes. Previous clinical studies suggest wide
      inter-individual variability of the effects of such AEDs. The options for
      antiepileptic treatment have dramatically expanded in the past decade and now
      allow tailoring of intervention for optimal management of individual patients.
      Current strategies to improve epilepsy care should include systematic monitoring
      to identify adverse effects of AEDs, and future approaches may involve creative
      applications of neuroimaging and genetic technologies to match patient
      characteristics to AED attributes.

PMID- 15557552
TI  - Random mutagenesis of the gene encoding a viral ligand for multiple cell entry
      receptors to obtain viral mutants altered for receptor usage.
AB  - Herpes simplex virus type 1 (HSV-1) can enter cells expressing any one of
      multiple entry receptors, including the herpesvirus entry mediator (HVEM), nectin
      1, and sites in heparan sulfate generated by specific 3-O-sulfotransferases. The
      viral ligand for these receptors is glycoprotein D (gD). To define structural
      requirements for functional interactions of gD with its receptors and to obtain
      viral mutants altered for receptor usage, we generated a library of HSV-1 mutants
      with random mutations in the gD gene. Viral isolates selected on a monkey cell
      line (Vero) were screened for the loss of ability to infect cells expressing each
      of the HSV-1 receptors. The 10 HSV-1 mutants obtained had 12 mutations in gD,
      affecting 11 amino acids. All mutations reduced or abrogated viral entry through
      HVEM and 3-O-sulfated heparan sulfate, indicating that similar features of gD are
      critical for functional interactions with both these receptors. None of the
      mutations reduced viral entry through nectin-1, whereas a subset of the mutations
      conferred ability to use nectin-2 as an entry receptor. These and other results
      show that features of gD, including conformation of the N terminus, critical for
      functional interactions with HVEM/3-O-sulfated heparan sulfate, differ from those
      critical for interactions with nectin-1.

PMID- 15557553
TI  - Subcellular distribution of enzyme I of the Escherichia coli
      phosphoenolpyruvate:glycose phosphotransferase system depends on growth
      conditions.
AB  - The phosphoenolpyruvate:glycose phosphotransferase system (PTS) participates in
      important functions in the bacterial cell, including the phosphorylation/uptake
      of PTS sugars. Enzyme I (EI), the first protein of the PTS complex, accepts the
      phosphoryl group from phosphoenolpyruvate, which is then transferred through a
      chain of proteins to the sugar. In these studies, a mutant GFP, enhanced yellow
      fluorescent protein (YFP), was linked to the N terminus of EI, giving Y-EI. Y-EI
      was active both in vitro (>/=90% compared with EI) and in vivo. Unexpectedly, the
      subcellular distribution of Y-EI varied significantly. Three types of
      fluorescence were observed: (i) diffuse (dispersed throughout the cell), (ii)
      punctate (concentrated in numerous discrete spots throughout the cell), and (iii)
      polar (at one or both ends of the cell). Cells from dense colonies grown on agar
      plates with LB broth or synthetic (Neidhardt) medium showed primarily bipolar or
      punctate fluorescence. In liquid culture, under carefully defined carbon-limiting
      growth conditions [ribose (non-PTS), mannitol (PTS sugar), or dl-lactate],
      cellular levels of enzymatically active Y-EI remain essentially constant for each
      carbon source, but fluorescence distribution depends on C source, cell density,
      growth phase, and apparently on "conditioned medium." Fluorescence was diffuse
      during exponential growth on LB or ribose/Neidhardt medium. On ribose they became
      punctate in the stationary phase, reverting to diffuse when more ribose was
      added. In LB, both Y-EI and a nonphosphorylatable mutant, H189Q-Y-EI, showed a
      diffuse fluorescence during growth, but, shortly after the addition of isopropyl
      beta-d-thiogalactopyranoside, Y-EI became bipolar; H189Q-Y-EI did not. The
      functions of EI sequestration remain to be determined.

PMID- 15557554
TI  - Activating Met mutations produce unique tumor profiles in mice with selective
      duplication of the mutant allele.
AB  - Tyrosine kinase-activating mutations in Met have been observed in hereditary
      papillary renal carcinomas as well as in other cancers. These mutations have been
      examined in several in vitro systems, where they cause constitutive Met
      activation, focus formation, and cell motility, and are tumorigenic in
      xenografts. To study the influence of these mutations on tumorigenesis in vivo,
      we generated mice with targeted mutations in the murine met locus. The following
      five mouse lines with mutant Met were created: WT, D1226N, Y1228C, M1248T, and
      M1248T/L1193V. We observed that mice harboring D1226N, Y1228C(,) and
      M1248T/L1193V mutations developed a high frequency of sarcomas and some
      lymphomas, whereas the M1248T mice developed carcinomas and lymphomas. Of
      considerable interest, we observed trisomy of chromosome 6 and duplication of the
      mutant met allele in a majority of the tumors, similar to what has been reported
      in patients with hereditary renal papillary carcinomas. These results demonstrate
      that activating Met mutations and met amplification play key roles in promoting
      tumorigenesis in vivo. Moreover, our findings show that different mutations in
      the Met kinase domain can influence the types of cancers that develop.

PMID- 15557555
TI  - Shifting paradigms: Herbivory and body size in lizards.

PMID- 15557556
TI  - Postmenopausal osteoporosis, T cells, and immune dysfunction.

PMID- 15557557
TI  - Is knowing always feeling?

PMID- 15557558
TI  - Experimental test of the birdsong error-correction model.
AB  - Adult zebra finches require auditory feedback to maintain their songs. It has
      been proposed that the lateral magnocellular nucleus of the anterior nidopallium
      (LMAN) mediates song plasticity based on auditory feedback. In this model,
      neurons in LMAN, tuned to the spectral and temporal properties of the bird's own
      song (BOS), are thought to compute the difference between the auditory feedback
      from the bird's vocalizations and an internal song template. This error
      correction signal is then used to initiate changes in the motor system that make
      future vocalizations a better match to the song template. This model was tested
      by recording from single LMAN neurons while manipulating the auditory feedback
      heard by singing birds. In contrast to the model predictions, LMAN spike patterns
      are insensitive to manipulations of auditory feedback. These results suggest that
      BOS tuning in LMAN is not used for error detection and constrain the nature of
      any error signal from LMAN to the motor system. Finally, LMAN neurons produce
      spikes locked precisely to the bird's song, independent of the auditory feedback
      heard by the bird. This finding suggests that a large portion of the input to
      this nucleus is from the motor control signals that generate the song rather than
      from auditory feedback.

PMID- 15557559
TI  - Defective lysosomal exocytosis and plasma membrane repair in Chediak
      Higashi/beige cells.
AB  - Plasma membrane resealing is a Ca(2+)-dependent process that involves the
      exocytosis of intracellular vesicles next to the wound site. Recent studies
      revealed that conventional lysosomes behave as Ca(2+)-regulated secretory
      compartments and play a central role in membrane resealing. These findings raised
      the possibility that the complex pathology of lysosomal diseases might also
      include defects in plasma membrane repair. Here, we investigated the capacity for
      lysosomal exocytosis and membrane resealing of fibroblasts derived from Chediak
      Higashi syndrome (CHS) patients, or from beige-J mice. By using a sensitive
      electroporation/fluorescence-activated cell sorter-based assay, we show that
      lysosomal exocytosis triggered by membrane wounding is impaired in both human
      Chediak-Higashi and mouse beige-J fibroblasts. Lysosomal exocytosis increased
      when the normal size of lysosomes was restored in beige-J cells by expression of
      the CHS/Beige protein. A similar effect was seen when the lysosomal enlargement
      in beige-J cells was reversed by treatment with E64d. In addition, the survival
      of Chediak-Higashi and beige-J fibroblasts after wounding was reduced, indicating
      that impaired lysosomal exocytosis inhibits membrane resealing in these mutant
      cells. Thus, the severe symptoms exhibited by CHS patients may also include
      defects in the ability of cells to repair plasma membrane lesions.

PMID- 15557560
TI  - Transcriptional regulation of human UGT1A1 gene expression: activated
      glucocorticoid receptor enhances constitutive androstane receptor/pregnane X
      receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid
      receptor-interacting protein 1.
AB  - UDP-glucuronosyltransferase (UGT) 1A1 glucuronidates endogenous metabolites, such
      as bilirubin, and exogenous substances, and plays a critical role in their
      detoxification and excretion. In a previous article, we described the
      phenobarbital response activity to a 290-base pair (bp) distal enhancer sequence
      (-3499/-3210) of the human UGT1A1 gene that is activated by the constitutive
      androstane receptor (CAR). Here, we show that dexamethasone at submicromolar
      concentrations enhances the pregnane X receptor (PXR) activator-mediated
      expression of the UGT1A1 gene and protein in HepG2 cells. We investigated the
      molecular mechanism of UGT1A1 induction by glucocorticoids at submicromolar
      concentrations and PXR activators and the functional cross-talk between the
      glucocorticoid receptor (GR) and CAR/PXR. The glucocorticoid-response element
      (GRE) was characterized by cotransfection experiments, site-directed mutagenesis,
      and electrophoretic mobility shift assays. Analysis of the human UGT1A1 promoter
      revealed GREs at -3404/-3389 and -3251/-3236 close to the CAR/PXR response
      element gtNR1 (-3382/-3367). Furthermore, in an in vitro reporter gene assay,
      dexamethasone effectively enhanced CAR/PXR-mediated transactivation of the 290-bp
      distal enhancer module in HepG2 cells and CV-1 cells in the presence of
      exogenously expressed GR and glucocorticoid receptor-interacting protein 1
      (GRIP1). In glutathione S-transferase pull-down experiments, CAR and PXR
      interacted with GRIP1. Together, these results demonstrate a rational mechanistic
      basis for UGT1A1 induction by glucocorticoids and PXR activators, showing that
      activated GR enhances CAR/PXR-mediated UGT1A1 regulation with the transcriptional
      cofactor GRIP1 and that GR may be involved synergistically in the xenobiotic
      responsive regulation of UGT1A1 by CAR/PXR.

PMID- 15557561
TI  - The nongenotropic synthetic ligand 4-estren-3alpha17beta-diol is a high-affinity
      genotropic androgen receptor agonist.
AB  - The nongenotropic ligand estren (Science 298:843-846, 2002) was evaluated for its
      transcriptional activity mediated by the human androgen receptor (AR). Our
      results show that estren can bind, translocate, transactivate, and regulate two
      known target genes of AR in androgen-responsive cell lines. Estren binds
      recombinant AR with 10-fold higher affinity than either estrogen receptor (ER)
      alpha or ERbeta. Estren-bound AR can translocate AR to the nucleus and stimulate
      the androgen response element-luciferase reporter activity with an efficacy
      similar to that of androgen. Estren also increased the expression of prostate
      specific antigen (PSA) in a dose-dependent manner in human LnCaP cells. Using
      chromatin immunoprecipitation analysis, we show that the estren-bound AR
      coimmunoprecipitates with a region of the PSA gene promoter. Therefore,
      cotreatment with an AR antagonist, bicalutamide, blocked the estren-induced
      increase in PSA expression. In contrast, phosphoinositol 3-kinase inhibitor
      wortmannin, or extracellular signal-regulated kinase inhibitor 1,4-diamino-2,3
      dicyano-1,4-bis(2-aminophynyltio)butadiene (U0126), and ER antagonist ICI-182780
      failed to block the effects of estren. In vivo analysis of estren's action on
      male-orchidectomized ICR mice revealed estren's AR agonist actions on the levator
      ani and seminal vesicle target tissues. Taken together, our results reveal the
      hitherto unidentified genotropic action of estren mediated by AR in androgen
      responsive cells and tissues.

PMID- 15557563
TI  - Views on recertification.

PMID- 15557564
TI  - Views on recertification.

PMID- 15557565
TI  - Views on recertification.

PMID- 15557567
TI  - Acute coronary syndromes.

PMID- 15557568
TI  - Acute coronary syndromes.

PMID- 15557569
TI  - Rethinking diabetes care in Canada.

PMID- 15557570
TI  - A question of ethics.

PMID- 15557571
TI  - Final evaluation results for the Fast-Check HIV rapid test kits.

PMID- 15557572
TI  - Clostridium difficile colitis: a marker for ischemic colitis?

PMID- 15557573
TI  - The doubts and fears of emergency physicians.

PMID- 15557576
TI  - For-profit clinics are legal but "no solution".

PMID- 15557579
TI  - Lawsuits mount in wake of rofecoxib (Vioxx) withdrawal.

PMID- 15557581
TI  - India's HIV-1 epidemic.

PMID- 15557582
TI  - Sports dermatology part 2: swimming and other aquatic sports.

PMID- 15557583
TI  - SARS outbreak in the Greater Toronto Area: the emergency department experience.

PMID- 15557584
TI  - Gonorrhea treatment guidelines in Canada: 2004 update.

PMID- 15557585
TI  - A man with an enlarging foot mass.

PMID- 15557586
TI  - Medical gels and the risk of serious infection.

PMID- 15557587
TI  - Initial viral load and the outcomes of SARS.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a novel
      coronavirus. It may progress to respiratory failure, and a significant proportion
      of patients die. Preliminary data suggest that a high viral load of the SARS
      coronavirus is associated with adverse outcomes in the intensive care unit, but
      the relation of viral load to survival is unclear. METHODS: We prospectively
      studied an inception cohort of 133 patients with virologically confirmed SARS who
      were admitted to 2 general acute care hospitals in Hong Kong from Mar. 24 to May
      4, 2003. The patients were followed until death or for a minimum of 90 days. We
      used Cox proportional hazard modelling to analyze potential predictors of
      survival recorded at the time of presentation, including viral load from
      nasopharyngeal specimens (measured by quantitative reverse transcriptase
      polymerase chain reaction [PCR] of the SARS-associated coronavirus). RESULTS:
      Thirty-two patients (24.1%) met the criteria for acute respiratory distress
      syndrome, and 24 patients (18.0%) died. The following baseline factors were
      independently associated with worse survival: older age (61-80 years) (adjusted
      hazard ratio [HR] 5.24, 95% confidence interval [CI] 2.03-13.53), presence of an
      active comorbid condition (adjusted HR 3.36, 95% CI 1.44-7.82) and higher initial
      viral load of SARS coronavirus, according to quantitative PCR of nasopharyngeal
      specimens (adjusted HR 1.21 per log10 increase in number of RNA copies per
      millilitre, 95% CI 1.06-1.39). INTERPRETATION: We found preliminary evidence that
      higher initial viral load is independently associated with worse prognosis in
      SARS. Mortality data for patients with SARS should be interpreted in light of
      age, comorbidity and viral load. These considerations will be important in future
      studies of SARS.

PMID- 15557588
TI  - The impact of SARS on a tertiary care pediatric emergency department.
AB  - BACKGROUND: The Greater Toronto Area (GTA) was considered a "hot zone" for severe
      acute respiratory syndrome (SARS) in 2003. In accordance with mandated city-wide
      infection control measures, the Hospital for Sick Children (HSC) drastically
      reduced all services while maintaining a fully operational emergency department.
      Because of the GTA health service suspensions and the overlap of SARS-like
      symptoms with many common childhood illnesses, this introduced the potential for
      a change in the volumes of patients visiting the emergency department of the only
      regional tertiary care children's hospital. METHODS: We compared HSC emergency
      department patient volumes, admission rates and length of stay in the emergency
      department in the baseline years of 2000-2002 (non-SARS years) with those in 2003
      (SARS year). The data from the prior years were modeled as a time series. Using
      an interrupted time series analysis, we compared the 2003 data for the periods
      before, during and after the SARS periods with the modeled data for significant
      differences in the 3 aforementioned outcomes of interest. RESULTS: Compared with
      the 2000-2002 data, we found no differences in visits, admission rates or length
      of stay in the pre-SARS period in 2003. There were significant decreases in
      visits and length of stay (p < 0.001) and increases in admission rates (p <
      0.001) during the periods in 2003 when there were new and active cases of SARS in
      the GTA. All 3 outcomes returned to expected estimates coincident with the
      absence of SARS cases from September to December 2003. INTERPRETATION: During the
      SARS outbreak in the GTA, the HSC emergency department experienced significantly
      reduced volumes of patients with low-acuity complaints. This gives insight into
      utilization rates of a pediatric emergency department during a time when there
      was additional perceived risk in using emergency department services and provides
      a foundation for emergency department preparedness policies for SARS-like public
      health emergencies.

PMID- 15557589
TI  - Health Canada's new guidelines for body weight classification in adults:
      challenges and concerns.

PMID- 15557590
TI  - Transparency in drug regulation: mirage or oasis?

PMID- 15557591
TI  - Responding to the needs of children with chronic health conditions in an era of
      health services reform.

PMID- 15557592
TI  - Tips for learners of evidence-based medicine: 3. Measures of observer variability
      (kappa statistic).

PMID- 15557593
TI  - A multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen is
      antiangiogenic, producing objective responses and survival benefit in a mouse
      model of cancer.
AB  - PURPOSE: A transgenic mouse model has revealed parameters of the angiogenic
      switch during multistep tumorigenesis of pancreatic islets, and demonstrated
      efficacy of antiangiogenic therapies. Pericytes have been revealed as
      functionally important for tumor neovasculature, using kinase inhibitors
      targeting their platelet-derived growth factor receptors (PDGFRs). Additionally,
      vascular endothelial growth factor receptor (VEGFR) inhibitors and metronomic
      chemotherapy show modest benefit against early- but not late-stage disease.
      MATERIALS AND METHODS: Seeking to improve efficacy against otherwise intractable
      end-stage pancreatic islet tumors, two receptor tyrosine kinase inhibitors,
      imatinib and SU11248, were used to disrupt PDGFR-mediated pericyte support of
      tumor endothelial cells in concert with maximum-tolerated dose (MTD) or
      metronomic chemotherapy and/or VEGFR inhibition. RESULTS: Imatinib, despite
      equivocal efficacy as monotherapy, reduced pericyte coverage of tumor vessels and
      enhanced efficacy in combination with metronomic chemotherapy or VEGFR
      inhibition. A regimen involving all three was even better. MTD using
      cyclophosphamide caused transitory regression, but then rapid regrowth, in
      contrast to metronomic cyclophosphamide plus imatinib, which produced stable
      disease. The MTD regimen elicited apoptosis of tumor cells but not endothelial
      cells, whereas the other regimens increased endothelial cell apoptosis concordant
      with efficacy. A "chemo-switch" protocol, involving sequential MTD and then
      metronomic chemotherapy, overlaid with multitargeted inhibition of PDGFR and
      VEGFR, gave complete responses and unprecedented survival advantage in this
      model. CONCLUSION: This study demonstrates a potentially tractable clinical
      strategy in a stringent preclinical model, wherein standard-of-care chemotherapy
      is followed by a novel maintenance regimen: PDFGR is targeted to disrupt pericyte
      support, while metronomic chemotherapy and/or VEGFR inhibitors target
      consequently sensitized endothelial cells, collectively destabilizing pre
      existing tumor vasculature and inhibiting ongoing angiogenesis.

PMID- 15557594
TI  - Practical management of patients with non-small-cell lung cancer treated with
      gefitinib.
AB  - PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal
      growth factor receptor tyrosine kinase, is indicated in patients with non-small
      cell lung cancer with tumors progressive after chemotherapy. The unique mechanism
      of action of this agent leads to distinctive patterns of response and toxicity in
      persons with lung cancer. Many of the principles of management relevant to
      gefitinib are distinct from those with conventional cytotoxic drugs. To meet this
      need, we present practical guidelines on the use of gefitinib in patients with
      non-small-cell lung cancer. METHODS: This article reviews gefitinib's
      indications, dosing, response phenomena, and patterns of relapse in individuals
      with radiographic response. RESULTS: We present our recommendations for the
      management of rash and diarrhea caused by this agent. CONCLUSION: This
      information can guide practitioners and help them inform their patients about
      what to expect when they receive gefitinib.

PMID- 15557595
TI  - ATP-binding cassette transporters are targets for the development of
      antibacterial vaccines and therapies.

PMID- 15557596
TI  - Enteropathogenic Escherichia coli infection triggers host phospholipid metabolism
      perturbations.
AB  - Enteropathogenic Escherichia coli (EPEC) specifically recognizes
      phosphatidylethanolamine (PE) on the outer leaflet of host epithelial cells. EPEC
      also induces apoptosis in epithelial cells, which results in increased levels of
      outer leaflet PE and increased bacterial binding. Consequently, it is of interest
      to investigate whether EPEC infection perturbs host cell phospholipid metabolism
      and whether the changes play a role in the apoptotic signaling. Our findings
      indicate that EPEC infection results in a significant increase in the epithelial
      cell PE level and a corresponding decrease in the phosphatidylcholine (PC) level.
      PE synthesis via both the de novo pathway and the serine decarboxylation pathway
      was enhanced, and de novo synthesis of phosphatidylcholine via CDP-choline was
      reduced. The changes were transitory, and the maximum change was noted after 4 to
      5 h of infection. Addition of exogenous PC or CDP-choline to epithelial cells
      prior to infection abrogated EPEC-induced apoptosis, suggesting that EPEC
      infection inhibits the CTP-phosphocholine cytidylyltransferase step in PC
      synthesis, which is reportedly inhibited during nonmicrobially induced apoptosis.
      On the other hand, incorporation of exogenous PE by the host cells enhanced EPEC
      induced apoptosis and necrosis without increasing bacterial adhesion. This is the
      first report that pathogen-induced apoptosis is associated with significant
      changes in PE and PC metabolism, and the results suggest that EPEC adhesion to a
      host membrane phospholipid plays a role in disruption of host phospholipid
      metabolism.

PMID- 15557597
TI  - Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter
      pylori: a new pathomechanism in H. pylori infection?
AB  - In Helicobacter pylori gastritis, neutrophil activation and migration, which play
      central roles in the pathogenesis of the disease, are regulated by the neutrophil
      attractant chemokines interleukin 8 (IL-8) and Groalpha, whose secretion is
      induced by H. pylori. However, the modulation of the corresponding chemokine
      receptors CXCR1 and CXCR2 on human neutrophils under the influence of H. pylori
      has not been investigated. Incubation of neutrophils with cag(+) and cag deletion
      H. pylori strains resulted in a complete downregulation of the CXCR1 and the
      CXCR2 receptors after 0.5 h, as tested by fluorescence-activated cell sorter
      analysis, independent of the cag status. Downregulation of CXCR1 and CXCR2 seems
      to occur via receptor internalization and rapid degradation, as shown by confocal
      microscopy and immunoblotting. Neither the proinflammatory cytokines IL-8 and
      tumor necrosis factor alpha produced by the neutrophils themselves nor H. pylori
      lipopolysaccharide, which are the known regulators of these two chemokine
      receptors, was responsible for the downregulation. Reverse transcription-PCR
      analysis showed that CXCR1 and CXCR2 mRNAs of neutrophils were reduced at a later
      time than the CXCR1 and CXCR2 proteins. Moreover, cag(+) H. pylori strains
      induced significantly stronger downregulation of CXCR1 and CXCR2 mRNAs than the
      cag deletion mutant. Therefore, receptor protein and mRNA downregulation seem to
      be mediated by two independent mechanisms. Data obtained by immunohistochemistry
      suggested that downmodulation of CXCR1 and CXCR2 on neutrophils may also occur in
      vivo in the human stomach during H. pylori infection. Downregulation of CXCR1 and
      CXCR2 expression on neutrophils in H. pylori infection by H. pylori itself may
      represent a new mechanism of modulating neutrophil migration and activation in
      the gastric mucosa.

PMID- 15557598
TI  - Yersinia enterocolitica adhesin A induces production of interleukin-8 in
      epithelial cells.
AB  - The major invasive factor of Yersinia enterocolitica, the invasin (Inv) protein,
      induces proinflammatory host cell responses, including interleukin-8 (IL-8)
      secretion from human epithelial cells, by engagement of beta1 integrins. The Inv
      triggered beta1 integrin signaling involves the small GTPase Rac; the activation
      of MAP kinases, such as p38, MEK1, and JNK; and the activation of the
      transcription factor NF-kappaB. In the present study, we demonstrate that Y.
      enterocolitica YadA, which is a major adhesin of Y. enterocolitica with
      pleiotropic virulence effects, induces IL-8 secretion in epithelial cells. The
      abilities of YadA and Inv to promote adhesion to and invasion of HeLa cells and
      to induce IL-8 production by the cells were investigated by expression of YadA
      and Inv in Escherichia coli. While YadA mediates efficacious adhesion to HeLa
      cells, it mediates marginal invasion compared with Inv. Both YadA and Inv trigger
      comparable levels of IL-8 production. Conformational changes of the YadA head
      domain by mutation of NSVAIG-S motifs, which abolish collagen binding, also
      abolish adhesion of Yersinia to HeLa cells and YadA-mediated IL-8 secretion.
      Furthermore, experiments in which blocking antibodies against beta1 integrins
      were used demonstrate that beta1 integrins are crucial for YadA-mediated IL-8
      secretion. Inhibitor studies demonstrate the involvement of small GTPases and MAP
      kinases, such as p38, MEK1, and JNK, indicating that beta1 integrin-dependent
      signaling mediated by Inv or YadA involves similar signaling pathways. These data
      present YadA, in addition to Inv, YopB, and Yersinia lipopolysaccharide, as a
      further inducer of proinflammatory molecules by which Y. enterocolitica might
      promote inflammatory tissue reactions.

PMID- 15557599
TI  - The major histocompatibility complex haplotype affects T-cell recognition of
      mycobacterial antigens but not resistance to Mycobacterium tuberculosis in C3H
      mice.
AB  - Both innate and adaptive immunity play an important role in host resistance to
      Mycobacterium tuberculosis infection. Although several studies have suggested
      that the major histocompatibility complex (MHC) haplotype affects susceptibility
      to infection, it remains unclear whether the modulation of T-cell immunity by the
      MHC locus determines the host's susceptibility to tuberculosis. To determine
      whether allelic differences in the MHC locus affect the T-cell immune response
      after M. tuberculosis infection, we infected inbred and H-2 congenic mouse
      strains by the respiratory route. The H-2 locus has a profound effect on the
      antigen-specific CD4+-T-cell response after M. tuberculosis infection. CD4+ T
      cells from infected mice of the H-2(b) haplotype produced more gamma interferon
      (IFN-gamma) after in vitro stimulation with mycobacterial antigens than mice of
      the H-2(k) haplotype. A higher level of IFN-gamma was also detected in
      bronchoalveolar lavage fluid from infected mice of the H-2(b) haplotype.
      Furthermore, C3.SW-H2(b)/SnJ mice generate and recruit activated T cells to the
      lung after infection. Despite a robust immune response, C3.SW-H2(b)/SnJ mice
      succumbed to infection early and were similarly susceptible to infection as other
      C3H (H-2(k)) substrains. These results suggest that although the MHC haplotype
      has a profound impact on the T-cell recognition of M. tuberculosis antigens, the
      susceptibility of C3H mice to infection is MHC independent.

PMID- 15557600
TI  - The mycobacterial heparin-binding hemagglutinin is a protective antigen in the
      mouse aerosol challenge model of tuberculosis.
AB  - The heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis is a
      surface-expressed adhesin that can affect binding to host cells via a unique,
      methylated, carboxyl-terminal, lysine-, alanine-, and proline-rich repeat region.
      It has been implicated in extrapulmonary dissemination of M. tuberculosis from
      the lung following the initial infection of the host. To assess the vaccine
      potential of this protein, purified preparations of HBHA were emulsified in a
      dimethyldioctadecylammonium bromide-monophosphoryl lipid A adjuvant and tested
      for the ability to reduce M. tuberculosis infection in the mouse aerosol
      challenge model for tuberculosis. The HBHA-containing vaccine gave a
      approximately 0.7-log reduction in CFU in both mouse lungs and spleens compared
      to adjuvant controls 28 days following challenge. Although a notable level of
      serum antibody to HBHA was elicited after three immunizations and the antibodies
      were able to bind to the surface of M. tuberculosis, passive immunization with
      monoclonal antibodies directed against HBHA did not protect in the challenge
      model. Compared to adjuvant controls, an elevated gamma interferon response was
      generated by splenic and lymph node-derived T cells from immunized mice in the
      presence of macrophages pulsed with purified HBHA or infected with live M.
      tuberculosis, suggesting that the effective immunity may be cell mediated.
      Efforts to construct effective recombinant HBHA vaccines in fast-growing
      Mycobacterium smegmatis have been unsuccessful so far, which indicates that
      distinctive posttranslational modifications present in the HBHA protein expressed
      by M. tuberculosis are critical for generating effective host immune responses.
      The vaccine studies described here demonstrate that HBHA is a promising new
      vaccine candidate for tuberculosis.

PMID- 15557601
TI  - Apical organelle discharge by Cryptosporidium parvum is temperature,
      cytoskeleton, and intracellular calcium dependent and required for host cell
      invasion.
AB  - The apical organelles in apicomplexan parasites are characteristic secretory
      vesicles containing complex mixtures of molecules. While apical organelle
      discharge has been demonstrated to be involved in the cellular invasion of some
      apicomplexan parasites, including Toxoplasma gondii and Plasmodium spp., the
      mechanisms of apical organelle discharge by Cryptosporidium parvum sporozoites
      and its role in host cell invasion are unclear. Here we show that the discharge
      of C. parvum apical organelles occurs in a temperature-dependent fashion. The
      inhibition of parasite actin and tubulin polymerization by cytochalasin D and
      colchicines, respectively, inhibited parasite apical organelle discharge.
      Chelation of the parasite's intracellular calcium also inhibited apical organelle
      discharge, and this process was partially reversed by raising the intracellular
      calcium concentration by use of the ionophore A23187. The inhibition of parasite
      cytoskeleton polymerization by cytochalasin D and colchicine and the depletion of
      intracellular calcium also decreased the gliding motility of C. parvum
      sporozoites. Importantly, the inhibition of apical organelle discharge by C.
      parvum sporozoites blocked parasite invasion of, but not attachment to, host
      cells (i.e., cultured human cholangiocytes). Moreover, the translocation of a
      parasite protein, CP2, to the host cell membrane at the region of the host cell
      parasite interface was detected; an antibody to CP2 decreased the C. parvum
      invasion of cholangiocytes. These data demonstrate that the discharge of C.
      parvum sporozoite apical organelle contents occurs and that it is temperature,
      intracellular calcium, and cytoskeleton dependent and required for host cell
      invasion, confirming that apical organelles play a central role in C. parvum
      entry into host cells.

PMID- 15557602
TI  - NK cells contribute to the control of Trypanosoma cruzi infection by killing free
      parasites by perforin-independent mechanisms.
AB  - The protozoan parasite Trypanosoma cruzi circulates in the blood as
      trypomastigotes and invades a variety of cells to multiply intracellularly as
      amastigotes. The acute phase leads to an immune response that restricts the
      proliferation of the parasite. However, parasites are able to persist in
      different tissues, which causes the pathology of Chagas' disease. Natural killer
      (NK) cells play an important role in innate resistance to a variety of pathogens.
      In the present study we analyzed whether NK cells participated in the control of
      experimental T. cruzi infection. NK cells were depleted from C57BL/6 mice by
      antiasialo antibodies. This treatment caused an increased parasitemia during the
      acute phase, but tissue parasite burdens were not significantly altered according
      to quantitative real-time PCR. Our results demonstrated that NK cells were
      activated during the initial phase of a T. cruzi infection and exhibited a
      contact-dependent antiparasitic activity against extracellular parasites that was
      independent from perforin. Thus, NK cells limit the propagation of the parasite
      by acting on circulating T. cruzi trypomastigotes.

PMID- 15557603
TI  - Vesicular transport is not required for the cytoplasmic pool of cholera toxin to
      interact with the stimulatory alpha subunit of the heterotrimeric g protein.
AB  - Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER)
      by retrograde vesicular transport. The catalytic A1 polypeptide of CT (CTA1) then
      crosses the ER membrane, enters the cytosol, ADP-ribosylates the stimulatory
      alpha subunit of the heterotrimeric G protein (Gsalpha) at the cytoplasmic face
      of the plasma membrane, and activates adenylate cyclase. The cytosolic pool of
      CTA1 may reach the plasma membrane and its Gsalpha target by traveling on
      anterograde-directed transport vesicles. We examined this possibility with the
      use of a plasmid-based transfection system that directed newly synthesized CTA1
      to either the ER lumen or the cytosol of CHO cells. Such a system allowed us to
      bypass the CT retrograde trafficking itinerary from the cell surface to the ER.
      Previous work has shown that the ER-localized pool of CTA1 is rapidly exported
      from the ER to the cytosol. Expression of CTA1 in either the ER or the cytosol
      led to the activation of Gsalpha, and Gsalpha activation was not inhibited in
      transfected cells exposed to drugs that inhibit vesicular traffic. Thus,
      anterograde transport from the ER to the plasma membrane is not required for the
      cytotoxic action of CTA1.

PMID- 15557604
TI  - Modulation of swarming and virulence by fatty acids through the RsbA protein in
      Proteus mirabilis.
AB  - After sensing external signals, Proteus mirabilis undergoes a multicellular
      behavior called swarming which is coordinately regulated with the expression of
      virulence factors. Here we report that exogenously added fatty acids could act as
      signals to regulate swarming in P. mirabilis. Specifically, while oleic acid
      enhanced swarming, some saturated fatty acids, such as lauric acid, myristic
      acid, palmitic acid, and stearic acid, inhibited swarming. We also found that
      expression of hemolysin, which has been shown to be coordinately regulated with
      swarming, was also inhibited by the above saturated fatty acids. Previously we
      identified a gene, rsbA, which may encode a histidine-containing
      phosphotransmitter of the bacterial two-component signaling system and act as a
      repressor of swarming and virulence factor expression in P. mirabilis. We found
      that while myristic acid, lauric acid, and palmitic acid exerted their inhibitory
      effect on swarming and hemolysin expression through an RsbA-dependent pathway,
      the inhibition by stearic acid was mediated through an RsbA-independent pathway.
      Biofilm formation and extracellular polysaccharide (EPS) production play an
      important role in P. mirabilis infection. We found that RsbA may act as a
      positive regulator of biofilm formation and EPS production. Myristic acid was
      found to slightly stimulate biofilm formation and EPS production, and this
      stimulation was mediated through an RsbA-dependent pathway. Together, these data
      suggest that fatty acids may act as environmental cues to regulate swarming and
      virulence in P. mirabilis and that RsbA may play an important role in this
      process.

PMID- 15557605
TI  - Resistance of Mycoplasma pulmonis to complement lysis is dependent on the number
      of Vsa tandem repeats: shield hypothesis.
AB  - The Vsa proteins are associated with the virulence of the murine respiratory
      pathogen Mycoplasma pulmonis. The antigens consist of a conserved N-terminal
      region that is combined with one of several different variable C-terminal regions
      comprised of tandem repeats. M. pulmonis strains that produce VsaA with about 40
      tandem repeats do not adhere to polystyrene or erythrocytes and are highly
      resistant to complement killing. Strains that produce VsaA with three tandem
      repeats adhere strongly to polystyrene and erythrocytes and are highly
      susceptible to complement killing. We report here that the resistance to
      complement lysis was not due to a lack of activation of the complement cascade.
      Isolation and analysis of M. pulmonis strains that produced Vsa proteins other
      than VsaA (VsaG and VsaI) with either long or short repeat regions indicated that
      adherence to polystyrene and resistance to complement were dependent on the
      length of the repeat region but not on the Vsa type. Furthermore, M. pulmonis Vsa
      variants were susceptible to the polypeptide pore-forming molecule gramicidin D,
      independent of the Vsa type and length. Collectively, the data indicate the Vsa
      proteins nonspecifically mediate M. pulmonis surface interactions and function to
      sterically hinder access of complement to the mycoplasma cell membrane while
      permitting access of smaller molecules.

PMID- 15557606
TI  - Rapid sequential changeover of expressed p44 genes during the acute phase of
      Anaplasma phagocytophilum infection in horses.
AB  - Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s
      have been hypothesized to go through antigenic variation, but the within-host
      dynamics of p44 expression has not been demonstrated. In the present study we
      investigated the composition and changes of p44 transcripts in the blood during
      the acute phase of well-defined laboratory A. phagocytophilum infections in naive
      equine hosts. Three traveling waves of sequential population changeovers of the
      p44 transcript species were observed within a single peak of rickettsemia of less
      than 1 month. During the logarithmic increase, the rapid switch-off of the
      initial dominant transcript p44-18 occurred regardless of whether the bacterium
      was transmitted by ticks or by intravenous inoculation. Each of the subsequently
      dominant p44 transcript species was phylogenetically dissimilar from p44-18.
      Development of antibody to the hypervariable region of P44-18 during the
      rickettsemia suggests the suppression of dominance of immuno-cross-reactive p44
      populations. When A. phagocytophilum was preincubated with plasma from the
      infected horse and then coincubated with HL-60 cells, the dominance of the p44-18
      transcript was rapidly suppressed in vitro and most of the newly emerged p44
      transcript species were previously undetected in this horse. This work provides
      experimental evidence of within-host p44 antigenic variation. Results suggest
      that the rapid and synchronized switch of expression is an intrinsic property of
      p44s reinitiated after transmission to naive mammalian hosts and shaped upon
      exposure to immune plasma.

PMID- 15557607
TI  - Salmonella enterica serovar Typhimurium infection induces cyclooxygenase 2
      expression in macrophages: involvement of Salmonella pathogenicity island 2.
AB  - Salmonella pathogenicity island 2 (SPI-2) is required for intramacrophage
      survival and systemic infection in mice. We have recently reported that
      Salmonella enterica causes activation of the protein kinase A (PKA) signaling
      pathway in a manner dependent on SPI-2, resulting in the upregulation of
      interleukin-10 expression in macrophages (K. Uchiya et al., Infect. Immun.
      72:1964-1973, 2004). We show in the present study the involvement of SPI-2 in a
      signal transduction pathway that induces the expression of cyclooxygenase 2 (COX
      2), an inducible enzyme involved in the synthesis of prostanoids. High levels of
      prostaglandin E(2) (PGE(2)) and prostacyclin (PGI(2)), which are known to
      activate the PKA signaling pathway via their receptors, were induced in J774
      macrophages infected with wild-type Salmonella compared to a strain carrying a
      mutation in the spiC gene, located within SPI-2. The increased production of both
      prostanoids was dependent on COX-2. COX-2 expression was dose dependently blocked
      by treatment with a specific inhibitor of the extracellular signal-regulated
      kinase 1/2 (ERK1/2) signaling pathway, and the phosphorylation level of ERK1/2
      was higher in macrophages infected with wild-type Salmonella compared to the spiC
      mutant. Taken together, these results indicate that Salmonella causes an SPI-2
      dependent ERK1/2 activation that leads to increased COX-2 expression, resulting
      in the upregulation of PGE(2) and PGI(2) production in macrophages. A COX-2
      inhibitor inhibited not only Salmonella-induced activation of the PKA signaling
      pathway but also growth of wild-type Salmonella within macrophages, suggesting
      that Salmonella utilizes the COX-2 pathway to survive within macrophages and that
      the mechanism involves activation of the PKA signaling pathway.

PMID- 15557608
TI  - Analysis of the immune response to Mycobacterium avium subsp. paratuberculosis in
      experimentally infected calves.
AB  - Johne's disease of cattle is widespread and causes significant economic loss to
      producers. Control has been hindered by limited understanding of the immune
      response to the causative agent, Mycobacterium avium subsp. paratuberculosis, and
      lack of an effective vaccine and sensitive specific diagnostic assays. The
      present study was conducted to gain insight into factors affecting the immune
      response to M. avium subsp. paratuberculosis. A persistent proliferative response
      to M. avium subsp. paratuberculosis purified protein derivative and soluble M.
      avium subsp. paratuberculosis antigens was detected in orally infected neonatal
      calves 6 months postinfection (p.i.) by flow cytometry (FC). CD4(+) T cells with
      a memory phenotype (CD45R0(+)) expressing CD25 and CD26 were the predominant cell
      type responding to antigens. Few CD8(+) T cells proliferated in response to
      antigens until 18 months p.i. gammadelta T cells did not appear to respond to
      antigen until 18 months p.i. The majority of WC1(+) CD2(-) and a few WC1(-)
      CD2(+) gammadelta T cells expressed CD25 at time zero. By 18 months, however,
      subsets of gammadelta T cells from both control and infected animals showed an
      increase in expression of CD25, ACT2, and CD26 in the presence of the antigens.
      Two populations of CD3(-) non-T non-B null cells, CD2(+) and CD2(-), proliferated
      in cell cultures from some control and infected animals during the study, with
      and without antigen. The studies clearly show multicolor FC offers a consistent
      reliable way to monitor the evolution and changes in the immune response to M.
      avium subsp. paratuberculosis that occur during disease progression.

PMID- 15557609
TI  - Bystander activation of CD8+ T lymphocytes during experimental mycobacterial
      infection.
AB  - Infection of C57BL/6 mice with Mycobacterium avium leads to the activation of
      both CD4+ and CD8+ gamma interferon (IFN-gamma)-producing T cells, although the
      CD8+ cells play no role in protection against infection. Using transfer of
      different lines of transgenic T cells with T-cell receptors (TCRs) which
      recognize irrelevant antigens, we show here that transferred CD8+ T cells from
      two of the three lines were activated to the same degree as the host cells,
      suggesting that the majority of the IFN-gamma-producing CD8+ T cells of the host
      represented bystander activation. The third line, specific for the male HY
      antigen, showed no activation. Activation required the participation of the CD28
      coreceptor on T cells and was unaffected by the removal of CD44(hi) (memory
      phenotype) T cells. The transferred CD8+ T cells proliferated in vivo, although
      this was not essential for IFN-gamma production. Taken together, these data are
      highly reminiscent of homeostatic proliferation of TCR transgenic T cells upon
      transfer to lymphopenic hosts, and suggest low-affinity stimulation through the
      TCR, possibly by self peptides. The findings are discussed in relation to
      homeostatic proliferation and their significance in the possible induction of
      autoimmune disease.

PMID- 15557610
TI  - Gamma interferon does not enhance clearance of Pseudomonas aeruginosa but does
      amplify a proinflammatory response in a murine model of postseptic
      immunosuppression.
AB  - Patients that have suffered a major injury may sustain a period of
      immunocompromise and altered Th1/Th2 cytokine balance that can predispose them to
      opportunistic infections. Pseudomonas aeruginosa is frequently a causative
      organism for nosocomial infections in critically ill patients and is associated
      with high mortality. We previously mimicked this clinical scenario by challenging
      mice with P. aeruginosa 5 days after a cecal ligation and puncture (CLP)
      procedure. Mice that were subjected to CLP had reduced ability to clear bacteria,
      significantly lower gamma interferon (IFN-gamma) concentrations in plasma, and
      significantly elevated levels of interleukin 10 (IL-10) in plasma in response to
      the Pseudomonas challenge compared to uninjured control mice. We investigated the
      significance of the alteration in IFN-gamma by administering recombinant IFN
      gamma to post-CLP mice at the time of Pseudomonas challenge and by challenging
      IFN-gamma knockout (IFN-gamma KO) mice with Pseudomonas. Administration of IFN
      gamma to post-CLP mice attenuated IL-10 secretion and enhanced IL-12 secretion
      but did not improve bacterial clearance or survival after Pseudomonas challenge.
      Furthermore, IFN-gamma KO mice had significantly higher plasma IL-10
      concentrations but did not exhibit impaired bacterial clearance or increased
      mortality following Pseudomonas challenge. These data indicate that systemic
      administration of IFN-gamma effectively reverses alterations in immune function
      that are commonly associated with immunosuppression in critically injured mice
      but does not improve bacterial clearance or survival following Pseudomonas
      challenge. Further, endogenous IFN-gamma does not appear to contribute
      significantly to early clearance of Pseudomonas bacteremia, nor does it affect
      the mortality rate after a lethal Pseudomonas challenge.

PMID- 15557611
TI  - Identification of two Mycobacterium marinum loci that affect interactions with
      macrophages.
AB  - Mycobacterium marinum is closely related to Mycobacterium tuberculosis, the cause
      of tuberculosis in humans. M. marinum has become an important model system for
      the study of the molecular mechanisms involved in causing tuberculosis in humans.
      Through molecular genetic analysis of the differences between pathogenic and
      nonpathogenic mycobacteria, we identified two loci that affect the ability of M.
      marinum to infect macrophages, designated mel(1) and mel(2). In silico analyses
      of the 11 putative genes in these loci suggest that mel(1) encodes secreted
      proteins that include a putative membrane protein and two putative
      transglutaminases, whereas mel(2) is involved in secondary metabolism or
      biosynthesis of fatty acids. Interestingly, mel(2) is unique to M. marinum and
      the M. tuberculosis complex and not present in any other sequenced mycobacterial
      species. M. marinum mutants with mutations in mel(1) and mel(2), constructed by
      allelic exchange, are defective in the ability to infect both murine and fish
      macrophage cell lines. These data suggest that the genes in mel(1) and mel(2) are
      important for the ability of M. marinum to infect host cells.

PMID- 15557612
TI  - Fine mapping of the N-terminal cytotoxicity region of Clostridium perfringens
      enterotoxin by site-directed mutagenesis.
AB  - Clostridium perfringens enterotoxin (CPE) has a unique mechanism of action that
      results in the formation of large, sodium dodecyl sulfate-resistant complexes
      involving tight junction proteins; those complexes then induce plasma membrane
      permeability alterations in host intestinal epithelial cells, leading to cell
      death and epithelial desquamation. Previous deletion and point mutational studies
      mapped CPE receptor binding activity to the toxin's extreme C terminus. Those
      earlier analyses also determined that an N-terminal CPE region between residues
      D45 and G53 is required for large complex formation and cytotoxicity. To more
      finely map this N-terminal cytotoxicity region, site-directed mutagenesis was
      performed with recombinant CPE (rCPE). Alanine-scanning mutagenesis produced one
      rCPE variant, D48A, that failed to form large complexes or induce cytotoxicity,
      despite having normal ability to bind and form the small complex. Two saturation
      variants, D48E and D48N, also had a phenotype resembling that of the D48A
      variant, indicating that both size and charge are important at CPE residue 48.
      Another alanine substitution rCPE variant, I51A, was highly attenuated for large
      complex formation and cytotoxicity, but rCPE saturation variants I51L and I51V
      displayed a normal large complex formation and cytotoxicity phenotype.
      Collectively, these mutagenesis results identify a core CPE sequence extending
      from residues G47 to I51 that directly participates in large complex formation
      and cytotoxicity.

PMID- 15557613
TI  - The Leishmania major LACK antigen with an immunodominant epitope at amino acids
      156 to 173 is not required for early Th2 development in BALB/c mice.
AB  - The Leishmania major LACK antigen contains an immunodominant epitope at amino
      acids 156 to 173 (LACK(156-173)) that is believed to nucleate the pathological
      Th2 immune response in susceptible BALB/c mice. To test this hypothesis, we
      generated L. major parasites that express a mutated LACK that fails to activate
      Vbeta4/Valpha8 T-cell receptor transgenic T cells specific for this epitope.
      Although mutant parasites attenuated the expansion of endogenous LACK-specific,
      interleukin-4 (IL-4)-expressing, CD4 T cells compared to wild-type parasites in
      vivo, the overall frequency of IL-4 and gamma interferon-secreting lymphocytes
      was similar to that elicited by wild-type L. major. Mutant parasites demonstrated
      diminished amastigote viability and delayed lesion development in mice, although
      parasites could be recovered over 200 days after infection. Complementation with
      a wild-type lack fusion construct partially rescued these defects, indicating a
      role for endogenous LACK in parasitism. Mice inoculated with mutant parasites
      were not protected against subsequent infection with wild-type L. major.

PMID- 15557614
TI  - Nitric oxide production and nitric oxide synthase activity in malaria-exposed
      Papua New Guinean children and adults show longitudinal stability and no
      association with parasitemia.
AB  - Individuals in areas of intense malaria transmission exhibit resistance (or
      tolerance) to levels of parasitemia in their blood that would normally be
      associated with febrile illness in malaria-naive subjects. The resulting level of
      parasitemia associated with illness (the pyrogenic threshold) is highest in
      childhood and lowest in adulthood. Clinical parallels between malarial and
      bacterial endotoxin tolerance have led to the supposition that both share common
      physiological processes, with nitric oxide (NO) proposed as a candidate mediator.
      The hypotheses that NO mediates tolerance and blood stage parasite killing in
      vivo were tested by determining its relationship to age and parasitemia cross
      sectionally and longitudinally in a population of 195 children and adults from
      Papua New Guinea encountering intense malaria exposure. Despite pharmacological
      clearance of asymptomatic parasitemia, NO production and mononuclear cell NO
      synthase (NOS) activity were remarkably stable within individuals over time, were
      not influenced by parasitemia, and varied little with age. These results contrast
      with previous smaller cross-sectional studies. Baseline NO production and NOS
      activity did not protect against recurrent parasitemia, consistent with previous
      data suggesting that NO does not have antiparasitic effects against blood stage
      infection in vivo. The NO indices studied were markedly higher in specimens from
      study subjects than in samples from Australian controls, and NOS activity was
      significantly associated with plasma immunoglobulin E levels, consistent with
      induction of NO by chronic exposure to other infections and/or host genetic
      factors. These results suggest that NO is unlikely to mediate killing of blood
      stage parasites in this setting and is unlikely to be the primary mediator in the
      acquisition or maintenance of malarial tolerance.

PMID- 15557615
TI  - Protective immunity against Eimeria acervulina following in ovo immunization with
      a recombinant subunit vaccine and cytokine genes.
AB  - A purified recombinant protein from Eimeria acervulina (3-1E) was used to
      vaccinate chickens in ovo against coccidiosis both alone and in combination with
      expression plasmids encoding the interleukin 1 (IL-1), IL-2, IL-6, IL-8, IL-15,
      IL-16, IL-17, IL-18, or gamma interferon (IFN-gamma) gene. When used alone,
      vaccination with 100 or 500 mug of 3-1E resulted in significantly decreased
      oocyst shedding compared with that in nonvaccinated chickens. Simultaneous
      vaccination of the 3-1E protein with the IL-1, -15, -16, or -17 gene induced
      higher serum antibody responses than 3-1E alone. To evaluate protective
      intestinal immunity, vaccinated birds were challenged with live E. acervulina
      oocysts 14 days posthatch, and fecal-oocyst shedding and body weight gain were
      determined as parameters of coccidiosis. Chickens vaccinated with 3-1E protein
      showed significantly lower oocyst shedding and normal body weight gain than
      nonvaccinated and infected controls. Simultaneous immunization with 3-1E and the
      IL-2, -15, -17, or -18 or IFN-gamma gene further reduced oocyst shedding compared
      with that achieved with 3-1E alone. These results provide the first evidence that
      in ovo vaccination with the recombinant 3-1E Eimeria protein induces protective
      intestinal immunity against coccidiosis, and this effect was enhanced by
      coadministration of genes encoding immunity-related cytokines.

PMID- 15557616
TI  - A heterologous DNA priming-Mycobacterium bovis BCG boosting immunization strategy
      using mycobacterial Hsp70, Hsp65, and Apa antigens improves protection against
      tuberculosis in mice.
AB  - Tuberculosis is responsible for >2 million deaths a year, and the number of new
      cases is rising worldwide. DNA vaccination combined with Mycobacterium bovis
      bacillus Calmette Guerin (BCG) represents a potential strategy for prevention of
      this disease. Here, we used a heterologous prime-boost immunization approach
      using a combination of DNA plasmids and BCG in order to improve the efficacy of
      vaccination against Mycobacterium tuberculosis infection in mice. As model
      antigens, we selected the M. tuberculosis Apa (for alanine-proline-rich antigen)
      and the immunodominant Hsp65 and Hsp70 mycobacterial antigens combined with BCG.
      We demonstrated that animals injected with a combination of DNA vectors
      expressing these antigens, when boosted with BCG, showed increased specific
      antimycobacterial immune responses compared to animals vaccinated with BCG alone.
      More importantly, the protection achieved with this regimen was also
      significantly better than with BCG alone.

PMID- 15557617
TI  - Redirecting the humoral immune response against Streptococcus mutans antigen P1
      with monoclonal antibodies.
AB  - The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine
      antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal
      immunization of mice was shown previously to alter the amount, specificity,
      isotype, and biological activity of anti-P1 antibodies. The present study was
      undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory
      activity when complexed with S. mutans and administered by a systemic route and
      to evaluate sera from immunized mice for the ability to inhibit adherence of S.
      mutans to immobilized human salivary agglutinin. All five MAbs tested influenced
      murine anti-P1 serum antibody responses in terms of subclass distribution and/or
      specificity. The effects varied depending on which MAb was used and its coating
      concentration. Two MAbs promoted a more effective, and two others a less
      effective, adherence inhibition response. An inverse relationship was observed
      between the ability of the MAbs themselves to inhibit adherence and the ability
      of antibodies elicited following immunization with immune complexes to inhibit
      adherence. Statistically significant correlations were demonstrated between the
      levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or
      IgG3, and the ability of sera from immunized animals to inhibit bacterial
      adherence. These results indicate that multiple anti-P1 MAbs can mediate changes
      in the immune response and that certain alterations are potentially more
      biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a
      useful strategy to improve the beneficial immune response against S. mutans.

PMID- 15557618
TI  - The C-terminal fragment of the internal 110-kilodalton passenger domain of the
      Hap protein of nontypeable Haemophilus influenzae is a potential vaccine
      candidate.
AB  - Nontypeable Haemophilus influenzae is a major causative agent of bacterial otitis
      media in children. H. influenzae Hap autotransporter protein is an adhesin
      composed of an outer membrane Hapbeta region and a moiety of an extracellular
      internal 110-kDa passenger domain called Hap(S). The Hap(S) moiety promotes
      adherence to human epithelial cells and extracellular matrix proteins, and it
      also mediates bacterial aggregation and microcolony formation. A recent work (D.
      L. Fink, A. Z. Buscher, B. A. Green, P. Fernsten, and J. W. St. Geme, Cell.
      Microbiol. 5:175-186, 2003) demonstrated that Hap(S) adhesive activity resides
      within the C-terminal 311 amino acids (the cell binding domain) of the protein.
      In this study, we immunized mice subcutaneously with recombinant proteins
      corresponding to the C-terminal region of Hap(S) from H. influenzae strains N187,
      P860295, and TN106 and examined the resulting immune response. Antisera against
      the recombinant proteins from all three strains not only recognized native Hap(S)
      purified from strain P860295 but also inhibited H. influenzae Hap-mediated
      adherence to Chang epithelial cells. Furthermore, when mice immunized
      intranasally with recombinant protein plus mutant cholera toxin CT-E29H were
      challenged with strain TN106, they were protected against nasopharyngeal
      colonization. These observations demonstrate that the C-terminal region of Hap(S)
      is capable of eliciting cross-reacting antibodies that reduce nasopharyngeal
      colonization, suggesting utility as a vaccine antigen for the prevention of
      nontypeable H. influenzae diseases.

PMID- 15557619
TI  - Relative contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to
      virulence in the lung.
AB  - Pseudomonas aeruginosa uses a type III secretion system to promote development of
      severe disease, particularly in patients with impaired immune defenses. While the
      biochemical and enzymatic functions of ExoU, ExoS, and ExoT, three effector
      proteins secreted by this system, are well defined, the relative roles of each
      protein in the pathogenesis of acute infections is not clearly understood. Since
      ExoU and ExoS are usually not secreted by the same strain, it has been difficult
      to directly compare the effects of these proteins during infection. In the work
      described here, several isogenic mutants of a bacterial strain that naturally
      secretes ExoU, ExoS, and ExoT were generated to carefully evaluate the relative
      contribution of each effector protein to pathogenesis in a mouse model of acute
      pneumonia. Measurements of mortality, bacterial persistence in the lung, and
      dissemination indicated that secretion of ExoU had the greatest impact on
      virulence while secretion of ExoS had an intermediate effect and ExoT had a minor
      effect. It is of note that these results conclusively show for the first time
      that ExoS is a virulence factor. Infection with isogenic mutants secreting wild
      type ExoS, ExoS defective in GTPase-activating protein (GAP) activity, or ExoS
      defective in ADP-ribosyltransferase activity demonstrated that the virulence of
      ExoS was largely dependent on its ADP-ribosyltransferase activity. The GAP
      activity of this protein had only a minor effect in vivo. The relative virulence
      associated with each of these type III effector proteins may have important
      prognostic implications for patients infected with P. aeruginosa.

PMID- 15557620
TI  - The Mycoplasma-derived macrophage-activating 2-kilodalton lipopeptide triggers
      global immune activation on nasal mucosa-associated lymphoid tissues.
AB  - A better knowledge on how immune responses are initiated in mucosal tissues would
      facilitate the design of new mucosal vaccines, as well as improve our
      understanding on host defense against infection. We investigated the mechanisms
      of adjuvanticity of the Mycoplasma-derived macrophage-activating 2-kDa
      lipopeptide (MALP-2), which binds to the heterodimer formed by the Toll-like
      receptors 2 and 6 (TLR2 and -6), at the level of the murine nasal mucosa
      associated lymphoid tissues (NALT). TLR2 expression analysis demonstrated that
      several cell types from the nasal cavity were able to overexpress this receptor,
      either constitutively (such as B cells) or after stimulation (i.e., T cells).
      MALP-2 stimulated a strong B-cell activation. In addition, the antigen
      presentation capacity of dendritic cells was improved after in vivo loading with
      antigen in the presence of MALP-2. We also observed an up-regulated expression of
      activation markers and adhesion molecules on T cells, suggesting that they have
      enhanced responsiveness and interaction potential. Quantitative reverse
      transcription-PCR analysis showed that MALP-2 administration resulted in the
      stimulation of a proinflammatory cascade. We observed an early up-regulated
      expression of IP-10, MCP-1, MCP-3, MIP-1alpha, MIP-2, and CCR-2 which was
      reversed within 36 h. The obtained results demonstrated that MALP-2 creates a
      reversible local microenvironment which promotes effective priming of T and B
      cells in the NALT.

PMID- 15557621
TI  - Induction of cationic chicken liver-expressed antimicrobial peptide 2 in response
      to Salmonella enterica infection.
AB  - Cationic antimicrobial peptides constitute part of the innate immune system and
      provide an essential role in the defense against infection. At present there is a
      paucity of information regarding the antimicrobial profile of the chicken (Gallus
      gallus). Using in silico studies, an expressed sequence tag (EST) clone was
      identified which encodes a novel cationic antimicrobial peptide, chicken liver
      expressed antimicrobial peptide 2 (cLEAP-2). The predicted amino acid sequence
      composed a prepropeptide, and the active peptide contained four conserved
      cysteine amino acids. The gene was localized to chromosome 13, and analysis of
      the genome revealed three exons separated by two introns. The cLEAP-2 gene was
      expressed in a number of chicken epithelial tissues including the small
      intestine, liver, lung, and kidney. Northern analysis identified liver-specific
      cLEAP-2 splice variants, suggesting some degree of tissue-specific regulation. To
      investigate whether cLEAP-2 expression was constitutive or induced in response to
      microbial infection, 4-day-old birds were orally infected with Salmonella.
      Analyses of cLEAP-2 expression by semiquantitative reverse transcription-PCR
      indicated that cLEAP-2 mRNA was upregulated significantly in the small intestinal
      tissues and the liver, indicative of direct and systemic responses. The
      antimicrobial activity of cLEAP-2 against Salmonella was analyzed in vitro with a
      time-kill assay and recombinant cLEAP-2. Interestingly Salmonella enterica
      serovar Typhimurium SL1344 showed increased susceptibility to the active cationic
      peptide (amino acids 37 to 76) compared to S. enterica serovar Typhimurium C5 and
      Salmonella enteritidis. Taken together, these data suggest that cationic cLEAP-2
      is part of the innate host defense mechanisms of the chicken.

PMID- 15557622
TI  - Long-term control of Mycobacterium bovis BCG infection in the absence of Toll
      like receptors (TLRs): investigation of TLR2-, TLR6-, or TLR2-TLR4-deficient
      mice.
AB  - Live mycobacteria have been reported to signal through both Toll-like receptor 2
      (TLR2) and TLR4 in vitro. Here, we investigated the role of TLR2 in the long-term
      control of the infection by the attenuated Mycobacterium, Mycobacterium bovis
      BCG, in vivo. We sought to determine whether the reported initial defect of
      bacterial control (K. A. Heldwein et al., J. Leukoc. Biol. 74:277-286, 2003)
      resolved in the chronic phase of BCG infection. Here we show that TLR2-deficient
      mice survived a 6-month infection period with M. bovis BCG and were able to
      control bacterial growth. Granuloma formation, T-cell and macrophage recruitment,
      and activation were normal. Furthermore, the TLR2 coreceptor, TLR6, is also not
      required since TLR6-deficient mice were able to control chronic BCG infection.
      Finally, TLR2-TLR4-deficient mice infected with BCG survived the 8-month
      observation period. Interestingly, the adaptive response of TLR2- and/or TLR4
      deficient mice seemed essentially normal on day 14 or 56 after infection, since T
      cells responded normally to soluble BCG antigens. In conclusion, our data
      demonstrate that TLR2, TLR4, or TLR6 are redundant for the control of M. bovis
      BCG mycobacterial infection.

PMID- 15557623
TI  - Immunostimulating properties of intragastrically administered Acetobacter-derived
      soluble branched (1,4)-beta-D-glucans decrease murine susceptibility to Listeria
      monocytogenes.
AB  - We previously found that AC-1, an extracellular polysaccharide, produced by
      Acetobacter xylinum and composed of (1,4)-beta-D-glucan with branches of glucosyl
      residues, showed a strong activity to induce production of interleukin-12 (IL-12)
      p40 and tumor necrosis factor alpha by macrophages in vitro via Toll-like
      receptor 4 (TLR-4) signaling. In the present study, we examined the effect of
      oral administration of AC-1 on protective immunity against Listeria
      monocytogenes. Mice were given AC-1 or phosphate-buffered saline (PBS)
      intragastrically 2 days before, on the day of, and 2 days after an
      intraperitoneal inoculation of L. monocytogenes. The survival rate of AC-1
      treated mice was significantly improved and bacterial growth in AC-1-treated mice
      was severely retarded compared to those of PBS-treated mice after infection with
      L. monocytogenes. IL-12 p40 levels in serum and magnitudes of CD4+ Th1 and CD8+
      Tc1 responses against Listeria antigen were significantly higher in AC-1-treated
      mice than in PBS-treated mice. The effect of AC-1 on antilisterial activity was
      diminished in C3H/HeJ mice carrying mutated TLR-4. Thus, AC-1, a potent IL-12
      inducer through TLR-4, enhanced protective immunity against L. monocytogenes via
      augmentation of Th1 responses. These results suggest that infectious processes
      driven by intracellular microorganisms could be prevented to develop by the (1,4)
      beta-D-glucan.

PMID- 15557624
TI  - Oral vaccination of BALB/c mice with Salmonella enterica serovar Typhimurium
      expressing Pseudomonas aeruginosa O antigen promotes increased survival in an
      acute fatal pneumonia model.
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial pneumonia. We compared
      the efficacies of oral and intraperitoneal (i.p.) vaccinations of BALB/c mice
      with attenuated Salmonella enterica serovar Typhimurium SL3261 expressing P.
      aeruginosa serogroup O11 O antigen to protect against P. aeruginosa infection in
      an acute fatal pneumonia model. Oral and i.p. vaccines elicited O11-specific
      serum immunoglobulin G (IgG) antibodies, but IgA was observed only after oral
      immunization. Challenge of orally vaccinated mice with an O11 strain (9882-80) at
      6 and 12 times the 50% lethal dose showed increased survival in mice that
      received the vaccine compared to phosphate-buffered saline (PBS)- and vector
      treated controls; no difference in survival was seen with a heterologous strain,
      6294 (serogroup O6). In addition, significant protection against 9882-80 was not
      observed in i.p. vaccinated animals. Bronchoalveolar lavage fluid taken from
      immunized mice harbored O11-specific IgA and IgG in orally immunized mice but
      only modest levels of IgG in i.p. vaccinated mice. To correlate protection,
      opsonophagocytosis assays were performed with pooled sera from orally immunized
      animals. Efficient killing of five O11 clinical isolates was observed, while no
      killing was noted with 6294, indicating that the recombinant SL3261 oral vaccine
      induces an O11-specific reaction. We next determined the ability of orally
      vaccinated animals to clear bacteria from their lungs. Following P. aeruginosa
      challenge, the numbers of viable bacteria were significantly fewer in orally
      vaccinated animals than in PBS- and vector-treated controls. Our results suggest
      that oral immunization with recombinant SL3261 is efficacious in protection
      against pneumonia caused by P. aeruginosa.

PMID- 15557625
TI  - Hemozoin differentially regulates proinflammatory cytokine production in human
      immunodeficiency virus-seropositive and -seronegative women with placental
      malaria.
AB  - Pregnant women are at an increased risk for malarial infection. Plasmodium
      falciparum accumulates in the placenta and is associated with dysregulated immune
      function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in
      the placenta and may modulate local immune function. In this study, the impact of
      hemozoin on cytokine production by intervillous blood mononuclear cells from
      malaria-infected placentas was investigated. There was a dose-dependent,
      suppressive effect of hemozoin on production of gamma interferon (IFN-gamma),
      with less of an effect on tumor necrosis factor alpha (TNF-alpha) and interleukin
      10, in human immunodeficiency virus-seronegative (HIV(-)) women. In contrast, IFN
      gamma and TNF-alpha production tended to increase in HIV-seropositive women with
      increasing hemozoin levels. Production patterns of cytokines, especially IFN
      gamma in HIV(-) women, followed different trends as a function of parasite
      density and hemozoin level. The findings suggest that the influences of hemozoin
      accumulation and high-density parasitemia on placental cytokine production are
      not equivalent and may involve different mechanisms, all of which may operate
      differently in the context of HIV infection. Cytokine production dysregulated by
      accumulation of hemozoin or high-density parasitemia may induce pathology and
      impair protective immunity in HIV-infected and -uninfected women.

PMID- 15557626
TI  - First-time isolation and characterization of a bacteriophage encoding the Shiga
      toxin 2c variant, which is globally spread in strains of Escherichia coli O157.
AB  - A bacteriophage encoding the Shiga toxin 2c variant (Stx2c) was isolated from the
      human Escherichia coli O157 strain CB2851 and shown to form lysogens on the E.
      coli K-12 laboratory strains C600 and MG1655. Production of Stx2c was found in
      the wild-type E. coli O157 strain and the K-12 lysogens and was inducible by
      growing bacteria in the presence of ciprofloxacin. Phage 2851 is the first
      reported viable bacteriophage which carries an stx(2c) gene. Electron micrographs
      of phage 2851 showed particles with elongated hexagonal heads and long flexible
      tails resembling phage lambda. Sequence analysis of an 8.4-kb region flanking the
      stx(2c) gene and other genetic elements revealed a mosaic gene structure, as
      found in other Stx phages. Phage 2851 showed lysis of E. coli K-12 strains
      lysogenic for Stx phages encoding Stx1 (H19), Stx2 (933W), Stx (7888), and Stx1c
      (6220) but showed superinfection immunity with phage lambda, presumably
      originating from the similarity of the cI repressor proteins of both phages.
      Apparently, phage 2851 integrates at a different chromosomal locus than Stx2
      phage 933W and Stx1 phage H19 in E. coli, explaining why Stx2c is often found in
      combination with Stx1 or Stx2 in E. coli O157 strains. Diagnostic PCR was
      performed to determine gene sequences specific for phage 2851 in wild-type E.
      coli O157 strains producing Stx2c. The phage 2851 q and o genes were frequently
      detected in Stx2c-producing E. coli O157 strains, indicating that phages related
      to 2851 are associated with Stx2c production in strains of E. coli O157 that were
      isolated in different locations and time periods.

PMID- 15557627
TI  - Severity of human african trypanosomiasis in East Africa is associated with
      geographic location, parasite genotype, and host inflammatory cytokine response
      profile.
AB  - The mechanisms underlying virulence in human African trypanosomiasis are poorly
      understood, although studies with experimental mice suggest that unregulated host
      inflammatory responses are associated with disease severity. We identified two
      trypanosomiasis foci with dramatically different disease virulence profiles. In
      Uganda, infections followed an acute profile with rapid progression to the late
      stage (meningoencephalitic infection) in the majority of patients (86.8%). In
      contrast, infections in Malawi were of a chronic nature, in which few patients
      progressed to the late stage (7.1%), despite infections of several months'
      duration. All infections were confirmed to be Trypanosoma brucei rhodesiense by
      testing for the presence of the serum resistance-associated (SRA) gene, but
      trypanosomes isolated from patients in Uganda or Malawi were distinguished by an
      SRA gene polymorphism. The two disease profiles were associated with markedly
      different levels of tumor necrosis factor alpha (TNF-alpha) and transforming
      growth factor beta (TGF-beta) in plasma. In Uganda but not Malawi early-stage TNF
      alpha was elevated, while in Malawi but not Uganda early-stage TGF-beta was
      elevated. Thus, rapid disease progression in Uganda is associated with TNF-alpha
      mediated inflammatory pathology, whereas in the milder disease observed in Malawi
      this may be ameliorated by counterinflammatory cytokines. These differing host
      responses may result either from differing virulence phenotypes of northern and
      southern trypanosomes or from immune response polymorphisms in the different host
      populations.

PMID- 15557628
TI  - Yersinia enterocolitica induces apoptosis and inhibits surface molecule
      expression and cytokine production in murine dendritic cells.
AB  - Yersinia enterocolitica evades innate immunity by expression of a variety of
      pathogenicity factors. Therefore, adaptive immunity including CD4(+) T cells
      plays an important role in defense against Y. enterocolitica. We investigated
      whether Y. enterocolitica might target dendritic cells (DC) involved in adaptive
      T-cell responses. For this purpose, murine DC were infected with Y.
      enterocolitica wild-type and mutant strains prior to incubation with ovalbumin
      (OVA) as antigen and 5-(6)-carboxyfluorescein diacetate N-succinimidyl ester
      labeled OVA-specific T cells from DO11.10 mice. While T-cell proliferation was
      partially affected by infection of DC with plasmid-cured and YopP-deficient
      Yersinia mutant strains, no T-cell proliferation occurred after infection of DC
      with wild-type Y. enterocolitica. Infection of DC with Y. enterocolitica wild
      type resulted in decreased up-regulation of major histocompatibility complex
      class II, CD54 (intercellular adhesion molecule 1), CD 80, and CD86 expression.
      Experiments with plasmid-cured Y. enterocolitica or a YopP-deficient mutant
      strain revealed that YopP accounts for inhibition of surface molecule expression.
      Wild-type Y. enterocolitica suppressed the release of KC, tumor necrosis factor
      alpha, interleukin-10 (IL-10), and IL-12 by DC, while infection of DC with
      plasmid-cured Y. enterocolitica or with the YopP-deficient mutant resulted in the
      production of these cytokines. Moreover, infection with wild-type Y.
      enterocolitica induced apoptosis in DC mediated by YopP. Apoptosis occurred
      despite translocation of NF-kappaB to the nucleus, as demonstrated by
      electromobility shift assays. Together, these data demonstrate that Y.
      enterocolitica targets functions of murine DC that are required for T-cell
      activation. This might contribute to evasion of adaptive immune responses by Y.
      enterocolitica.

PMID- 15557629
TI  - Streptococcal pyrogenic exotoxin B-induced apoptosis in a549 cells is mediated by
      a receptor- and mitochondrion-dependent pathway.
AB  - It has been shown that streptococcal pyrogenic exotoxin B (SPE B) can induce
      cells to undergo apoptosis. The present study is to dissect the role of SPE B
      protease and SPE B protein in the apoptotic process of A549 cells and to
      elucidate the SPE B-induced apoptotic pathway. Recombinant SPE B (rSPE B) and
      C192S, a mutant of SPE B without protease activity, were expressed in Escherichia
      coli and purified by using an affinity column. The apoptosis of A549 cells was
      assayed by propidium iodide staining, followed by flow cytometry analysis. Our
      results showed that SPE B induced apoptosis in a dose-dependent manner, whereas
      C192S did not. When cells were pretreated with rSPE B (2 mug/ml) for as briefly
      as 5 min and then incubated with C192S of 28 kDa, an apoptosis that is
      proportional to the period of pretreatment was observed but not with C192S of 42
      kDa. These results suggest that the extracellular protease activity of rSPE B is
      required for the initiation of apoptosis and that the size of SPE B is important
      for an effective induction of apoptosis. The time course analysis revealed that
      molecules activated in apoptosis were in the following order: caspase-8 (1.5 h),
      t-Bid (2.5 h), Bax (3 h), cytochrome c release (6 h), caspase-9 (7 h), and
      caspase-3 (8 h). The overexpression of Bcl-2 inhibited depolarization of
      mitochondrial membrane, cytochrome c release, and apoptosis. The results of the
      present study suggest that SPE B-induced apoptosis is mediated through a receptor
      like mechanism and a mitochondrion-dependent pathway.

PMID- 15557630
TI  - Polymorphisms in the Chlamydia trachomatis cytotoxin locus associated with ocular
      and genital isolates.
AB  - Chlamydia trachomatis is a strict human pathogen producing infections that cause
      medically important chronic inflammatory diseases, such as blinding trachoma and
      tubal factor infertility. Isolates exist as serotypes that fall into distinct
      biologic and pathological groups corresponding to differences in infection tissue
      tropism and invasion properties. Paradoxically, genome sequencing of several
      diverse strains has revealed a remarkable level of genomic synteny, suggesting
      that minor genetic differences determine the pathogen host- and tissue-specific
      infection characteristics. To better understand the genetic basis of chlamydial
      pathobiologic diversity, we performed comparative DNA-DNA microarray genomic
      hybridizations with all 15 C. trachomatis serovariants. We found there are few
      major genetic differences among the 15 serovars. An exception was the cytotoxin
      locus located in the plasticity zone, a region that exhibited significant
      polymorphisms among serovars. We therefore sequenced this region from all 15
      serovars. The cytotoxin gene was interrupted by extensive mutations and deletions
      among the different serovars; however, three basic open reading frame motifs were
      discovered that correlated with noninvasive oculotropic, urogenitotropic, and
      invasive serovars. Of interest, only noninvasive genitotropic serovars possessed
      an intact N-terminal portion of the putative toxin gene. This region contains the
      UDP-glucose binding domain and the glycosyltransferase domain required for
      enzymatic activity of the clostridial toxin homologs, suggesting a role in
      urogenital infection or pathogenesis.

PMID- 15557631
TI  - Rhodococcus equi-infected macrophages are recognized and killed by CD8+ T
      lymphocytes in a major histocompatibility complex class I-unrestricted fashion.
AB  - The goal of this research was to examine the role of cytotoxic T lymphocytes
      (CTL) in the control of Rhodococcus equi and specifically to determine if R. equi
      specific CD8+ CTL occurred in the blood of immune horses. Equine peripheral blood
      mononuclear cells stimulated with antigen-presenting cells either infected with
      R. equi or exposed to soluble R. equi antigen lysed R. equi-infected target
      cells. Lysis was decreased to background by depletion of either CD2+ or CD3+
      cells, indicating that the effector cell had a T-lymphocyte, but not NK cell,
      phenotype. Stimulation induced an increased percentage of CD8+ T cells in the
      effector population, and depletion of CD8+ T cells resulted in significantly
      decreased lysis of infected targets. Killing of R. equi-infected macrophages by
      effector cells was equally effective against autologous and equine leukocyte
      antigen A (classical major histocompatibility complex [MHC] class I) mismatched
      targets. To evaluate potential target antigens, target cells were infected with
      either virulent (80.6-kb plasmid-containing) or avirulent (plasmid-cured) R.
      equi. The degree of lysis was not altered by the presence of the plasmid,
      providing evidence that the virulence plasmid, which is required for survival
      within macrophages, was not necessary for recognition and killing of R. equi
      infected cells. These data indicate that immunocompetent adult horses develop R.
      equi-specific CD8+ CTL, which may play a role in immunity to R. equi. The
      apparent lack of restriction via classical MHC class I molecules suggests a novel
      or nonclassical method of antigen processing and presentation, such as
      presentation by CD1 or other nonclassical MHC molecules.

PMID- 15557632
TI  - A mutant of Mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A
      is attenuated in mice but retains vaccinogenic potential.
AB  - The fbpA and fbpB genes encoding the 85A and 85B proteins of Mycobacterium
      tuberculosis H37Rv, respectively, were disrupted, the mutants were examined for
      their ability to survive, and the strain lacking 85A (DeltafbpA) was tested for
      its ability to immunize mice. The DeltafbpA mutant was attenuated in mice after
      intravenous or aerosol infection, while replication of the DeltafbpB mutant was
      similar to that of the wild type. Complementation of the fbpA gene in DeltafbpA
      restored its ability to grow in the lungs of mice. The DeltafbpA mutant induced a
      stronger expression of pulmonary mRNA messages in mice for tumor necrosis factor
      alpha, interleukin-1 beta (IL-1beta), gamma interferon, IL-6, IL-2, and inducible
      nitric oxide (NO) synthase, which led to its decline, while H37Rv persisted
      despite strong immune responses. H37Rv and DeltafbpA both induced NO in
      macrophages and were equally susceptible to NO donors, although DeltafbpA was
      more susceptible in vitro to peroxynitrite and its growth was enhanced by NO
      inhibitors in mice and macrophages. Aerosol-infected mice, which cleared a low
      dose DeltafbpA infection, resisted a challenge with virulent M. tuberculosis.
      Mice subcutaneously immunized with DeltafbpA or Mycobacterium bovis BCG and
      challenged with M. tuberculosis also showed similar levels of protection, marked
      by a reduction in the growth of challenged M. tuberculosis. The DeltafbpA mutant
      was thus attenuated, unlike DeltafbpB, but was also vaccinogenic against
      tuberculosis. Attenuation was incomplete, however, since DeltafbpA revived in
      normal mice after 370 days, suggesting that revival was due to immunosenescence
      but not compensation by the fbpB or fbpC gene. Antigen 85A thus affects
      susceptibility to peroxynitrite in M. tuberculosis and appears to be necessary
      for its optimal growth in mice.

PMID- 15557633
TI  - Adaptation of the endogenous Salmonella enterica serovar Typhi clyA-encoded
      hemolysin for antigen export enhances the immunogenicity of anthrax protective
      antigen domain 4 expressed by the attenuated live-vector vaccine strain CVD 908
      htrA.
AB  - Bacterial live-vector vaccines aim to deliver foreign antigens to the immune
      system and induce protective immune responses, and surface-expressed or secreted
      antigens are generally more immunogenic than cytoplasmic constructs. We
      hypothesize that an optimum expression system will use an endogenous export
      system to avoid the need for large amounts of heterologous DNA encoding
      additional proteins. Here we describe the cryptic chromosomally encoded 34-kDa
      cytolysin A hemolysin of Salmonella enterica serovar Typhi (ClyA) as a novel
      export system for the expression of heterologous antigens in the supernatant of
      attenuated Salmonella serovar Typhi live-vector vaccine strains. We constructed a
      genetic fusion of ClyA to the reporter green fluorescent protein and showed that
      in Salmonella serovar Typhi CVD 908-htrA, the fusion protein retains biological
      activity in both domains and is exported into the supernatant of an exponentially
      growing live vector in the absence of detectable bacterial lysis. The utility of
      ClyA for enhancing the immunogenicity of an otherwise problematic antigen was
      demonstrated by engineering ClyA fused to the domain 4 (D4) moiety of Bacillus
      anthracis protective antigen (PA). A total of 11 of 15 mice immunized
      intranasally with Salmonella serovar Typhi exporting the protein fusion
      manifested fourfold or greater rises in serum anti-PA immunoglobulin G, compared
      with only 1 of 16 mice immunized with the live vector expressing cytoplasmic D4
      (P = 0.0002). In addition, the induction of PA-specific gamma interferon and
      interleukin 5 responses was observed in splenocytes. This technology offers
      exceptional versatility for enhancing the immunogenicity of bacterial live-vector
      vaccines.

PMID- 15557634
TI  - Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides.
AB  - The innate immune system plays a critical role in the defense of areas exposed to
      microorganisms. There is an increasing body of evidence indicating that
      antimicrobial peptides and proteins (APs) are one of the most important weapons
      of this system and that they make up the protective front for the respiratory
      tract. On the other hand, it is known that pathogenic organisms have developed
      countermeasures to resist these agents such as reducing the net negative charge
      of the bacterial membranes. Here we report the characterization of a novel
      mechanism of resistance to APs that is dependent on the bacterial capsule
      polysaccharide (CPS). Klebsiella pneumoniae CPS mutant was more sensitive than
      the wild type to human neutrophil defensin 1, beta-defensin 1, lactoferrin,
      protamine sulfate, and polymyxin B. K. pneumoniae lipopolysaccharide O antigen
      did not play an important role in AP resistance, and CPS was the only factor
      conferring protection against polymyxin B in strains lacking O antigen. In
      addition, we found a significant correlation between the amount of CPS expressed
      by a given strain and the resistance to polymyxin B. We also showed that K.
      pneumoniae CPS mutant bound more polymyxin B than the wild-type strain with a
      concomitant increased in the self-promoted pathway. Taken together, our results
      suggest that CPS protects bacteria by limiting the interaction of APs with the
      surface. Finally, we report that K. pneumoniae increased the amount of CPS and
      upregulated cps transcription when grown in the presence of polymyxin B and
      lactoferrin.

PMID- 15557635
TI  - Antigenicity and immunogenicity of a synthetic oligosaccharide-protein conjugate
      vaccine against Haemophilus influenzae type b.
AB  - Polysaccharide-protein conjugates as vaccines have proven to be very effective in
      preventing Haemophilus influenzae type b infections in industrialized countries.
      However, cost-effective technologies need to be developed for increasing the
      availability of anti-H. influenzae type b vaccines in countries from the
      developing world. Consequently, vaccine production with partially synthetic
      antigens is a desirable goal for many reasons. They may be rigidly controlled for
      purity and effectiveness while at the same time being cheap enough that they may
      be made universally available. We describe here the antigenicity and
      immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein
      conjugates in laboratory animals. The serum of H. influenzae type b-immunized
      animals recognized our synthetic H. influenzae type b antigens to the same extent
      as the native bacterial capsular polysaccharide. Compared to the anti-H.
      influenzae type b vaccine employed, these synthetic versions induced similar
      antibody response patterns in terms of titer, specificity, and functional
      capacity. The further development of synthetic vaccines will meet urgent needs in
      the less prosperous parts of the world and remains our major goal.

PMID- 15557636
TI  - Interactions of pulmonary collectins with Bordetella bronchiseptica and
      Bordetella pertussis lipopolysaccharide elucidate the structural basis of their
      antimicrobial activities.
AB  - Surfactant proteins A (SP-A) and D (SP-D) play an important role in the innate
      immune defenses of the respiratory tract. SP-A binds to the lipid A region of
      lipopolysaccharide (LPS), and SP-D binds to the core oligosaccharide region. Both
      proteins induce aggregation, act as opsonins for neutrophils and macrophages, and
      have direct antimicrobial activity. Bordetella pertussis LPS has a branched core
      structure and a nonrepeating terminal trisaccharide. Bordetella bronchiseptica
      LPS has the same structure, but lipid A is palmitoylated and there is a repeating
      O-antigen polysaccharide. The ability of SP-A and SP-D to agglutinate and
      permeabilize wild-type and LPS mutants of B. pertussis and B. bronchiseptica was
      examined. Previously, wild-type B. pertussis was shown to resist the effects of
      SP-A; however, LPS mutants lacking the terminal trisaccharide were susceptible to
      SP-A. In this study, SP-A was found to aggregate and permeabilize a B.
      bronchiseptica mutant lacking the terminal trisaccharide, while wild-type B.
      bronchiseptica and mutants lacking only the palmitoyl transferase or O antigen
      were resistant to SP-A. Wild-type B. pertussis and B. bronchiseptica were both
      resistant to SP-D; however, LPS mutants of either strain lacking the terminal
      trisaccharide were aggregated and permeabilized by SP-D. We conclude that the
      terminal trisaccharide protects Bordetella species from the bactericidal
      functions of SP-A and SP-D. The O antigen and palmitoylated lipid A of B.
      bronchiseptica play no role in this resistance.

PMID- 15557637
TI  - Diversity and host range of Shiga toxin-encoding phage.
AB  - Shiga toxin 2 (Stx2) from the foodborne pathogen Escherichia coli O157:H7 is
      encoded on a temperate bacteriophage. Toxin-encoding phages from C600::933W and
      from six clinical E. coli O157:H7 isolates were characterized for PCR
      polymorphisms, phage morphology, toxin production, and lytic and lysogenic
      infection profiles on O157 and non-O157 serotype E. coli. The phages were found
      to be highly variable, and even phages isolated from strains with identical
      pulsed-field gel electrophoresis profiles differed. Examination of cross-plaquing
      and lysogeny profiles further substantiated that each phage is distinct;
      reciprocal patterns of susceptibility and resistance were not observed and it was
      not possible to define immunity groups. The interaction between Shiga toxin
      encoding phage and intestinal E. coli was examined. Lytic infection was assessed
      by examining Shiga toxin production following overnight incubation with phage.
      While not common, lytic infection was observed, with a more-than-1,000-fold
      increase in Stx2 seen in one case, demonstrating that commensal E. coli cells can
      amplify Shiga toxin if they are susceptible to infection by the Shiga toxin
      encoding phages. Antibiotic-resistant derivatives of the Stx2-encoding phages
      were used to examine lysogeny. Different phages were found to lysogenize
      different strains of intestinal E. coli. Lysogeny was found to occur more
      commonly than lytic infection. The presence of a diverse population of Shiga
      toxin-encoding phages may increase the pathogenic fitness of E. coli O157:H7.

PMID- 15557638
TI  - Characterization of a defensin from the sand fly Phlebotomus duboscqi induced by
      challenge with bacteria or the protozoan parasite Leishmania major.
AB  - Antimicrobial peptides are major components of the innate immune response of
      epithelial cells. In insect vectors, these peptides may play a role in the
      control of gut pathogens. We have analyzed antimicrobial peptides produced by the
      sand fly Phlebotomus duboscqi, after challenge by injected bacteria or feeding
      with bacteria or the protozoan parasite Leishmania major. A new hemolymph peptide
      with antimicrobial activity was identified and shown to be a member of the insect
      defensin family. Interestingly, this defensin exhibits an antiparasitic activity
      against the promastigote forms of L. major, which reside normally within the sand
      fly midgut. P. duboscqi defensin could be induced by both hemolymph or gut
      infections. Defensin mRNA was induced following infection by wild-type L. major,
      and this induction was much less following infections with L. major knockout
      mutants that survive poorly in sand flies, due to specific deficiencies in
      abundant cell surface glycoconjugates containing phosphoglycans (including
      lipophosphoglycan). The ability of gut pathogens to induce gut as well as fat
      body expression of defensin raises the possibility that this antimicrobial
      peptide might play a key role in the development of parasitic infections.

PMID- 15557639
TI  - BBE02 disruption mutants of Borrelia burgdorferi B31 have a highly transformable,
      infectious phenotype.
AB  - We constructed highly transformable and infectious Borrelia burgdorferi B31 by
      inactivating BBE02, a putative restriction-modification gene on the linear
      plasmid lp25. The low-passage-number B31 clones 5A4 (containing all plasmids) and
      5A18 (lp28-4(-) lp56(-)) were used for this study, and BBE02 was disrupted by
      homologous recombination. The transformation efficiency with the shuttle vector
      pBSV2C03::gntDeltakan was increased from <1 to approximately 10 colonies per mug
      of DNA for 5A4 and 5A4 BBE02::Kan(r) and from 14 to approximately 600 colonies
      per mug of DNA for 5A18 and 5A18 BBE02::Kan(r). lp25, which is required for
      infectivity in mice, was retained in BBE02 mutants transformed with
      pBSV2C03::gntDeltakan, but lp25 was not detected in transformants of the parental
      clones 5A4 and 5A18. BBE02 disruptants and pBSV2C03::gntDeltakan transformants of
      these clones remained infectious in C3H/HeN mice, and the 50% infective doses of
      the BBE02 disruptants were <10(2) organisms per mouse. The inactivation of BBE02
      thus eliminates a transformation barrier for infectious B. burgdorferi B31 and
      will provide a valuable tool for studying the virulence factors of Lyme disease.

PMID- 15557640
TI  - Truncation of fibronectin-binding proteins in Staphylococcus aureus strain Newman
      leads to deficient adherence and host cell invasion due to loss of the cell wall
      anchor function.
AB  - Staphylococcus aureus fibronectin-binding proteins (FnBPs) play a critical role
      in S. aureus pathogenesis. FnBPs mediate adhesion to fibronectin and invasion of
      mammalian cells, including epithelial, endothelial, and fibroblastic cells, by
      fibronectin bridging to the host cell fibronectin receptor integrin
      (alpha(5))beta(1). Strain Newman is a laboratory strain frequently used for
      genetic, functional, and in vivo studies. However, despite pronounced production
      of FnBPs, strain Newman is only weakly adherent to immobilized Fn and weakly
      invasive. We examined whether these effects are due to a structural difference of
      FnBPs. Here, we show that both fnbA(Newman) and fnbB(Newman) contain a centrally
      located point mutation resulting in a stop codon. This leads to a truncation of
      both FnBPs at the end of the C domain at identical positions. Most likely, the
      stop codon occurred first in fnbB(Newman) and was subsequently transferred to
      fnbA(Newman) by replacement of the entire region encompassing the C, D, and W
      domains with the respective sequence of fnbB(Newman). Using heterologous
      expression in Staphylococcus carnosus, we found that truncated FnBPs were
      completely secreted into the culture medium and not anchored to the cell wall,
      since they lack the sortase motif (LPETG). Consequently, this led to a loss of
      FnBP-dependent functions, such as strong adhesion to immobilized fibronectin,
      binding of fibrinogen, and host cell invasion. This mutation may explain some of
      the earlier reported conflicting data with strain Newman. Thus, care should be
      taken when drawing negative conclusions about the role of FnBPs as a virulence
      factor in a given model.

PMID- 15557641
TI  - Human antibody responses to a Chlamydia-secreted protease factor.
AB  - We have previously identified a chlamydia-secreted protein (designated chlamydial
      proteasome/protease-like activity factor, or CPAF) in the cytosol of chlamydia
      infected cells. Although CPAF is known to degrade host transcription factors
      required for major histocompatibility complex antigen expression in cultured
      cells, it is not clear whether CPAF is produced and maintains similar functions
      in humans infected with chlamydial organisms. We now report that CPAF does not
      preexist in chlamydial organisms and that CPAF synthesis requires live organism
      replication in cultured cells. Mice inoculated with live, but not mice inoculated
      with dead, chlamydial organisms produced a strong antibody response to CPAF,
      correlating CPAF-specific antibody production with CPAF synthesis in animals.
      Sera from women diagnosed with Chlamydia trachomatis cervicitis displayed higher
      levels of antibodies to CPAF than to either chlamydial major outer membrane
      protein or heat shock protein 60, suggesting that CPAF is both produced and
      immunogenic during human chlamydial infection.

PMID- 15557642
TI  - Distinct roles of reactive nitrogen and oxygen species to control infection with
      the facultative intracellular bacterium Francisella tularensis.
AB  - Reactive nitrogen species (RNS) and reactive oxygen species (ROS) are important
      mediators of the bactericidal host response. We investigated the contribution of
      these two mediators to the control of infection with the facultative
      intracellular bacterium Francisella tularensis. When intradermally infected with
      the live vaccine strain F. tularensis LVS, mice deficient in production of RNS
      (iNOS(-/-) mice) or in production of ROS by the phagocyte oxidase (p47(phox-/-)
      mice) showed compromised resistance to infection. The 50% lethal dose (LD(50))
      for iNOS(-/-) mice was <20 CFU, and the LD(50) for p47(phox-/-) mice was 4,400
      CFU, compared to an LD(50) of >500,000 CFU for wild-type mice. The iNOS(-/-) mice
      survived for 26.4 +/- 1.8 days, and the p47(phox-/-) mice survived for 10.1 +/-
      1.3 days. During the course of infection, the serum levels of gamma interferon
      (IFN-gamma) and interleukin-6 were higher in iNOS(-/-) and p47(phox-/-) mice than
      in wild-type mice. Histological examination of livers of iNOS(-/-) mice revealed
      severe liver pathology. Splenocytes obtained 5 weeks after primary infection from
      antibiotic-treated iNOS(-/-) mice showed an in vitro recall response that was
      similar in magnitude and greater secretion of IFN-gamma compared to cells
      obtained from wild-type mice. In summary, mice lacking expression of RNS or ROS
      showed extreme susceptibility to infection with F. tularensis LVS. The roles of
      RNS and ROS seemed to be distinct since mice deficient in production of ROS
      showed dissemination of infection and died during the early phase of infection,
      whereas RNS deficiency led to severe liver pathology and a contracted course of
      infection.

PMID- 15557643
TI  - Synovial fibroblasts infected with Salmonella enterica serovar Typhimurium
      mediate osteoclast differentiation and activation.
AB  - The mechanisms whereby arthritogenic organisms may induce cartilage and bone
      erosions in infection-triggered arthritis remain unknown. In this study, we asked
      whether an arthritogenic organism could contribute to osteoclast differentiation
      and activation through regulation of the receptor activator of NF-kappaB ligand
      (RANKL) in synovial fibroblasts. Rat synovial fibroblasts were infected in vitro
      with Salmonella enterica serovar Typhimurium and monitored over time. The
      expression of RANKL in resting and infected synovial fibroblasts was quantified
      by reverse transcription-PCR and Western blotting. Osteoclast progenitors,
      isolated from femurs of 8-week-old rats and cultured in the presence of
      macrophage colony-stimulating factor, were cocultured with either infected or
      noninfected synovial fibroblasts for 2 to 4 days. Differentiation and maturation
      of osteoclasts were determined by morphology and tartrate-resistant acid
      phosphatase (TRAP) staining and by a bone resorption bioassay. RANKL expression
      was undetectable in resting synovial fibroblasts but was dose-dependently
      upregulated in cells after Salmonella infection. Osteoprotegerin was
      constitutively expressed by synovial fibroblasts and was not upregulated by
      infection. Further, we observed the formation of multinucleated TRAP-positive
      cells and formation of bone resorption pits in cocultures of bone marrow-derived
      osteoclast precursors with synovial fibroblasts infected with Salmonella but not
      with heat-killed Salmonella or noninfected cells. Arthritogenic bacteria may
      alter bone structure via synovial fibroblast intermediaries, since infected
      synovial fibroblasts (i) upregulate RANKL expression and (ii) enhance osteoclast
      precursor maturation into multinucleated, TRAP-positive, bone-resorbing,
      osteoclast-like cells. These data provide a link between infection and
      osteoclastogenesis. A better understanding of infection-mediated osteoclast
      differentiation and activation may provide new therapeutic strategies for
      inflammatory joint disease.

PMID- 15557644
TI  - Evolutionary and functional relationships of colonization factor antigen i and
      other class 5 adhesive fimbriae of enterotoxigenic Escherichia coli.
AB  - Colonization factor antigen I (CFA/I) is the archetype of eight genetically
      related fimbriae of enterotoxigenic Escherichia coli (ETEC) designated class 5
      fimbriae. Assembled by the alternate chaperone pathway, these organelles comprise
      a rigid stalk of polymerized major subunits and an apparently tip-localized minor
      adhesive subunit. We examined the evolutionary relationships of class 5-specific
      structural proteins and correlated these with functional properties. We sequenced
      the gene clusters encoding coli surface antigen 4 (CS4), CS14, CS17, CS19, and
      putative colonization factor antigen O71 (PCFO71) and analyzed the deduced
      proteins and the published homologs of CFA/I, CS1, and CS2. Multiple alignment
      and phylogenetic analysis of the proteins encoded by each operon define three
      subclasses, 5a (CFA/I, CS4, and CS14), 5b (CS1, CS17, CS19, and PCFO71), and 5c
      (CS2). These share distant evolutionary relatedness to fimbrial systems of three
      other genera. Subclass divisions generally correlate with distinguishing in vitro
      adherence phenotypes of strains bearing the ETEC fimbriae. Phylogenetic
      comparisons of the individual structural proteins demonstrated greater
      intrasubclass conservation among the minor subunits than the major subunits. To
      correlate this with functional attributes, we made antibodies against CFA/I and
      CS17 whole fimbriae and maltose-binding protein fusions with the amino-terminal
      half of the corresponding minor subunits. Anti-minor subunit Fab preparations
      showed hemagglutination inhibition (HAI) of ETEC expressing homologous and
      intrasubclass heterologous colonization factors while anti-fimbrial Fab fractions
      showed HAI activity limited to colonization factor-homologous ETEC. These results
      were corroborated with similar results from the Caco-2 cell adherence assay. Our
      findings suggest that the minor subunits of class 5 fimbriae may be superior to
      whole fimbriae in inducing antiadhesive immunity.

PMID- 15557645
TI  - Toll-like receptor 9 can be expressed at the cell surface of distinct populations
      of tonsils and human peripheral blood mononuclear cells.
AB  - Unmethlylated CpG dinucleotides induce a strong T-helper-1-like inflammatory
      response, presumably mediated by Toll-like receptor 9 (TLR9). However, the nature
      and cellular localization of TLR9 in primary human cells remain controversial.
      Here we demonstrate, using flow cytometry and immunofluorescence microscopy
      techniques, that TLR9 can be expressed at the cell surface. The primary human
      cell subsets that were positive for TLR9 expression were distinct depending on
      the tissues analyzed. Specifically, in human peripheral blood mononuclear cells
      (PBMC) the majority of cell surface TLR9(+) cells were confined to the major
      histocompatibility complex (MHC) class II(+) CD19(-) populations that express
      CD11c and/or CD14, whereas in tonsils the same gated population contained
      primarily MHC class II(+) CD19(+) cells. Cells positive for surface expression
      represented a minor fraction of the total cell populations examined, varying
      between 2 and 10%. In addition, we found that TLR9 expression at the surface of
      PBMC was up-regulated approximately fourfold following stimulation with the gram
      negative bacterial cell wall component lipopolysaccharide, suggesting a potential
      modulatory role of TLR4 agonists on TLR9 expression. Taken together, these data
      validate human TLR9 expression at the surface of primary cells, in addition to
      the previously described intracellular localization. Further, our results suggest
      that human antigen-presenting cells comprise the major cell populations
      expressing cell surface TLR9.

PMID- 15557646
TI  - The pH 6 antigen is an antiphagocytic factor produced by Yersinia pestis
      independent of Yersinia outer proteins and capsule antigen.
AB  - The pH 6 antigen (pH 6 Ag; PsaA) of Yersinia pestis has been shown to be a
      virulence factor. In this study, we set out to investigate the possible function
      of Y. pestis PsaA in a host cell line, RAW264.7 mouse macrophages, in order to
      better understand the role it might play in virulence. Y. pestis KIM5 derivatives
      with and without the pCD1 plasmid and their psaA isogenic counterparts and
      Escherichia coli HB101 and DEta5alpha carrying a psaA clone or a vector control
      were used for macrophage infections. Macrophage-related bacteria and gentamicin
      resistant intracellular bacteria generated from plate counting and direct
      microscopic examinations were used to evaluate these RAW264.7 macrophage
      infections. Y. pestis psaA isogenic strains did not show any significant
      difference in their abilities to associate with or bind to mouse macrophage
      cells. However, expression of psaA appeared to significantly reduce phagocytosis
      of both Y. pestis and E. coli by mouse macrophages (P < 0.05). Furthermore, we
      found that complementation of psaA mutant Y. pestis strains could completely
      restore the ability of the bacteria to resist phagocytosis. Fluorescence
      microscopy following differential labeling of intracellular and extracellular Y.
      pestis revealed that significantly lower numbers of psaA-expressing bacteria were
      located inside the macrophages. Enhanced phagocytosis resistance was specific for
      bacteria expressing psaA and did not influence the ability of the macrophages to
      engulf other bacteria. Our data demonstrate that Y. pestis pH 6 Ag does not
      enhance adhesion to mouse macrophages but rather promotes resistance to
      phagocytosis.

PMID- 15557647
TI  - Identification of a novel virulence factor in Burkholderia cenocepacia H111
      required for efficient slow killing of Caenorhabditis elegans.
AB  - Burkholderia cenocepacia H111, which was isolated from a cystic fibrosis patient,
      employs a quorum-sensing (QS) system, encoded by cep, to control the expression
      of virulence factors as well as the formation of biofilms. The QS system is
      thought to ensure that pathogenic traits are expressed only when the bacterial
      population density is high enough to overwhelm the host before it is able to
      mount an efficient response. While the wild-type strain effectively kills the
      nematode Caenorhabditis elegans, the pathogenicity of mutants with defective
      quorum sensing is attenuated. To date, very little is known about the cep
      regulated virulence factors required for nematode killing. Here we report the
      identification of a cep-regulated gene, whose predicted amino acid sequence is
      highly similar to the QS-regulated protein AidA of the plant pathogen Ralstonia
      solanacearum. By use of polyclonal antibodies directed against AidA, it is
      demonstrated that the protein is expressed in the late-exponential phase and
      accumulates during growth arrest. We show that B. cenocepacia H111 AidA is
      essential for slow killing of C. elegans but has little effect on fast killing,
      suggesting that the protein plays a role in the accumulation of the strain in the
      nematode gut. Thus, AidA appears to be required for establishing an infection
      like process rather than acting as a toxin. Furthermore, evidence is provided
      that AidA is produced not only by B. cenocepacia but also by many other strains
      of the Burkholderia cepacia complex.

PMID- 15557648
TI  - Differential regulation of inflammatory cytokine secretion by human dendritic
      cells upon Chlamydia trachomatis infection.
AB  - Chlamydia trachomatis is an obligate intracellular gram-negative bacterium
      responsible for a wide spectrum of diseases in humans. Both genital and ocular C.
      trachomatis infections are associated with tissue inflammation and pathology.
      Dendritic cells (DC) play an important role in both innate and adaptive immune
      responses to microbial pathogens and are a source of inflammatory cytokines. To
      determine the potential contribution of DC to the inflammatory process, human DC
      were infected with C. trachomatis serovar E or L2. Both C. trachomatis serovars
      were found to infect and replicate in DC. Upon infection, DC up-regulated the
      expression of costimulatory (B7-1) and cell adhesion (ICAM-1) molecules.
      Furthermore, chlamydial infection induced the secretion of interleukin-1beta (IL
      1beta), IL-6, IL-8, IL-12p70, IL-18, and tumor necrosis factor alpha (TNF-alpha).
      The mechanisms involved in Chlamydia-induced IL-1beta and IL-18 secretion
      differed from those of the other cytokines. Chlamydia-induced IL-1beta and IL-18
      secretion required infection with viable bacteria and was associated with the
      Chlamydia-induced activation of caspase-1 in infected host cells. In contrast,
      TNF-alpha and IL-6 secretion did not require that the Chlamydia be viable,
      suggesting that there are at least two mechanisms involved in the Chlamydia
      induced cytokine secretion in DC. Interestingly, an antibody to Toll-like
      receptor 4 inhibited Chlamydia-induced IL-1beta, IL-6, and TNF-alpha secretion.
      The data herein demonstrate that DC can be infected by human C. trachomatis
      serovars and that chlamydial components regulate the secretion of various
      cytokines in DC. Collectively, these data suggest that DC play a role in the
      inflammatory processes caused by chlamydial infections.

PMID- 15557649
TI  - Development of a system to study CD4+-T-cell responses to transgenic ovalbumin
      expressing Toxoplasma gondii during toxoplasmosis.
AB  - The study of the immune response to Toxoplasma gondii has provided numerous
      insights into the role of T cells in resistance to intracellular infections.
      However, the complexity of this eukaryote pathogen has made it difficult to
      characterize immunodominant epitopes that would allow the identification of T
      cells with a known specificity for parasite antigens. As a consequence, analysis
      of T-cell responses to T. gondii has been based on characterization of the
      percentage of T cells that express an activated phenotype during infection and on
      the ability of these cells to produce cytokines in response to complex mixtures
      of parasite antigens. In order to study specific CD4(+) T cells responses to T.
      gondii, recombinant parasites that express a truncated ovalbumin (OVA) protein,
      in either a cytosolic or a secreted form, were engineered. In vitro and in vivo
      studies reveal that transgenic parasites expressing secreted OVA are able to
      stimulate T-cell receptor-transgenic OVA-specific CD4(+) T cells to proliferate,
      express an activated phenotype, and produce gamma interferon (IFN-gamma).
      Furthermore, the adoptive transfer of OVA-specific T cells into IFN-gamma(-/-)
      mice provided enhanced protection against infection with the OVA-transgenic (but
      not parental) parasites. Together, these studies establish the utility of this
      transgenic system to study CD4(+)-T-cell responses during toxoplasmosis.

PMID- 15557650
TI  - Transcriptional profiling of lipopolysaccharide-induced acute lung injury.
AB  - Mortality associated with acute lung injury (ALI) induced by lipopolysaccharide
      (LPS) remains high in humans, warranting improved treatment and prevention
      strategies. ALI is characterized by the expression of proinflammatory mediators
      and extensive neutrophil influx into the lung, followed by severe lung damage.
      Understanding the pathogenesis of LPS-induced ALI is a prerequisite for designing
      better therapeutic strategies. In the present study, we used microarrays to gain
      a global view of the transcriptional responses of the lung to LPS in a mouse
      model of ALI that mimics ALI in humans. A total of 71 inflammation-associated
      genes were up-regulated in LPS-treated lungs, including a chemokine, LPS-induced
      CXC chemokine (LIX), whose role in the induction of ALI is unknown. Most of the
      inflammatory genes peaked at 2 h post-LPS treatment. Real-time reverse
      transcription-PCR confirmed the LPS-induced up-regulation of selected genes
      identified by microarray analysis, including LIX. The up-regulation of LIX, tumor
      necrosis factor alpha, and macrophage inflammatory protein 2 was confirmed at the
      protein level by enzyme-linked immunosorbent assays. To determine the role of LIX
      in the induction of ALI, we used both exogenous LIX and a LIX blocking antibody.
      Exogenous LIX alone elicited a neutrophil influx in the lungs, and the anti-LIX
      antibody attenuated the LPS-induced neutrophil accumulation in the lungs. Taken
      together, the results of our study demonstrate for the first time the temporal
      expression of inflammatory genes during LPS-induced ALI and suggest that early
      therapeutic intervention is crucial to attenuate lung damage. Moreover, we
      identified a role for LIX in the induction of ALI, and therefore LIX may serve as
      a novel therapeutic target for the minimization of ALI.

PMID- 15557651
TI  - Identification of a novel Anaplasma marginale appendage-associated protein that
      localizes with actin filaments during intraerythrocytic infection.
AB  - The rickettsial pathogen Anaplasma marginale assembles an actin filament bundle
      during intracellular infection. Unlike other bacterial pathogens that generate
      actin filament tails, A. marginale infects mature erythrocytes, and the F-actin
      appendages are assembled on the cytoplasmic surface of a vacuole containing
      several organisms. To identify A. marginale molecules associated with these
      filaments, two complementary approaches were used: matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry and tandem mass
      spectrometry of A. marginale proteins identified with an appendage-specific
      monoclonal antibody and expression screening of an A. marginale phage library.
      Amino acid and nucleotide sequences were mapped to a full-length gene in the
      genome of the St. Maries strain of A. marginale; the correct identification was
      confirmed by expression of full-length recombinant protein and its reactivity
      with appendage-specific antibodies. Interestingly, there is marked variation in
      the abilities of diverse A. marginale strains to assemble the F-actin appendages.
      Comparison of four strains, the Florida, Illinois, St. Maries, and Virginia
      strains, revealed substantial polymorphism in the gene encoding the appendage
      associated protein, with amino acid sequence identity of as low as 34% among
      strains. However, this variation does not underlie the differences in expression,
      as there is no specific polymorphism associated with loss of ability to assemble
      actin appendages. In contrast, the ability to assemble an actin filament bundle
      reflected dramatic strain-specific differences in the expression level of the
      appendage-associated protein. Understanding how this protein influences the cycle
      of invasion, replication, and egress in the host cell may provide new insights
      into pathogen-host interactions.

PMID- 15557652
TI  - Characterization of immunodominant and potentially protective epitopes of
      Mannheimia haemolytica serotype 1 outer membrane lipoprotein PlpE.
AB  - Mannheimia haemolytica serotype 1 (S1) is the most common bacterial isolate found
      in shipping fever pneumonia in beef cattle. Currently used vaccines against M.
      haemolytica do not provide complete protection against the disease. Research with
      M. haemolytica outer membrane proteins (OMPs) has shown that antibodies to one
      particular OMP from S1, PlpE, may be important in immunity. In a recently
      published work, members of our laboratory showed that recombinant PlpE (rPlpE) is
      highly immunogenic when injected subcutaneously into cattle and that the acquired
      immunity markedly enhanced resistance to experimental challenge (A. W. Confer, S.
      Ayalew, R. J. Panciera, M. Montelongo, L. C. Whitworth, and J. D. Hammer, Vaccine
      21:2821-2829, 2003). The objective of this work was to identify epitopes of PlpE
      that are responsible for inducing the immune response. Western blot analysis of a
      series of rPlpE with nested deletions on both termini with bovine anti-PlpE
      hyperimmune sera showed that the immunodominant region is located close to the N
      terminus of PlpE. Fine epitope mapping, in which an array of overlapping 13-mer
      synthetic peptides attached to a derivatized cellulose membrane was probed with
      various affinity-purified anti-PlpE antibodies, identified eight highly reactive
      regions, of which region 2 (R2) was identified as the specific epitope. The R2
      region is comprised of eight imperfect repeats of a hexapeptide (QAQNAP) and is
      located between residues 26 and 76. Complement-mediated bactericidal activity of
      affinity-purified anti-PlpE bovine antibodies confirmed that antibodies directed
      against the R2 region are effective in killing M. haemolytica.

PMID- 15557653
TI  - Antifungal immune reactivity in nasal polyposis.
AB  - As a fungal etiology has been proposed to underlie severe nasal polyposis, the
      present study was undertaken to assess local antifungal immune reactivity in
      nasal polyposis. For this purpose, microbial colonization, along with the pattern
      of T helper 1 (Th1)/Th2 cytokine production and Toll-like receptor (TLR)
      expression, was evaluated in patients with nasal symptoms and with and without
      polyposis and in healthy subjects. The results show that Th2 reactivity was a
      common finding for patients with nasal polyposis regardless of the presence of
      microbes. The production of interleukin-10 was elevated in patients with
      bacterial and, particularly, fungal colonization, while both TLR2 expression and
      TLR4 expression were locally impaired in microbe-colonized patients. Eosinophils
      and neutrophils, highly recruited in nasal polyposis, were found to exert potent
      antifungal effector activities toward conidia and hyphae of the fungus and to be
      positively regulated by TLR2 or TLR4 stimulation. Therefore, a local imbalance
      between activating and deactivating signals to effector cells may likely
      contribute to fungal pathogenicity and the expression of local immune reactivity
      in nasal polyposis.

PMID- 15557654
TI  - Regulators encoded in the Escherichia coli type III secretion system 2 gene
      cluster influence expression of genes within the locus for enterocyte effacement
      in enterohemorrhagic E. coli O157:H7.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 subverts host cells through a
      type III secretion system encoded by the locus for enterocyte effacement (LEE).
      Genome sequencing of this pathotype revealed the existence of a gene cluster
      encoding components of a second cryptic type III secretion system, E. coli type
      III secretion system 2 (ETT2). Recently, we showed that the ETT2 gene cluster is
      present in whole or in part in the majority of E. coli strains but is unable to
      encode a functional secretion system in most strains, including EHEC O157:H7.
      However, here we show that mutational inhibition of two regulatory genes (ECs3720
      or etrA and ECs3734 or eivF) from the ETT2 cluster in EHEC O157:H7 leads to
      greatly increased secretion of proteins encoded by the LEE and to increased
      adhesion to human intestinal cells. Studies in which transcriptional fusions and
      microarrays were used indicated that EtrA and EivF exert profound negative
      effects on gene transcription within the LEE. Consistent with these observations,
      expression of these regulators in an EHEC O26:H- strain led to suppression of
      protein secretion under LEE-inducing conditions. These findings provide fresh
      examples of the influence of mobile genetic elements on regulation of the LEE and
      of cross talk between type III secretion system gene clusters. In addition, they
      provide a cautionary tale because they show that the effects of regulatory genes
      can outlive widespread decay of other genes in a functionally coherent gene
      cluster, a phenomenon that we have named the "Cheshire cat effect." It also seems
      likely that variations in the ETT2 regulator repertoire might account for strain
      to-strain variation in secretion of LEE-encoded proteins.

PMID- 15557655
TI  - Mannose-resistant Proteus-like fimbriae are produced by most Proteus mirabilis
      strains infecting the urinary tract, dictate the in vivo localization of
      bacteria, and contribute to biofilm formation.
AB  - Proteus mirabilis, an etiologic agent of complicated urinary tract infections,
      expresses mannose-resistant Proteus-like (MR/P) fimbriae whose expression is
      phase variable. Here we examine the role of these fimbriae in biofilm formation
      and colonization of the urinary tract. The majority of wild-type P. mirabilis
      cells in transurethrally infected mice produced MR/P fimbriae. Mutants that were
      phase-locked for either constitutive expression (MR/P ON) or the inability to
      express MR/P fimbriae (MR/P OFF) were phenotypically distinct and swarmed at
      different rates. The number of P. mirabilis cells adhering to bladder tissue did
      not appear to be affected by MR/P fimbriation. However, the pattern of adherence
      to the bladder surface was strikingly different. MR/P OFF colonized the lamina
      propria underlying exfoliated uroepithelium, while MR/P ON colonized the luminal
      surfaces of bladder umbrella cells and not the exfoliated regions. Wild-type P.
      mirabilis was usually found colonizing intact uroepithelium, but it occasionally
      adhered to exfoliated areas. MR/P ON formed significantly more biofilm than
      either P. mirabilis HI4320 (P = 0.03) or MR/P OFF (P = 0.05). MR/P OFF was able
      to form a biofilm similar to that of the wild type. MR/P ON formed a three
      dimensional biofilm structure as early as 18 h after the initiation of the
      biofilm, while MR/P OFF and the wild type did not. After 7 days, however, P.
      mirabilis HI4320 formed a 65-mum-thick biofilm, while the thickest MR/P ON and
      MR/P OFF biofilms were only 12 mum thick. We concluded that MR/P fimbriae are
      expressed by most P. mirabilis cells infecting the urinary tract, dictate the
      localization of bacteria in the bladder, and contribute to biofilm formation.

PMID- 15557656
TI  - Use of translational fusion of the MrpH fimbrial adhesin-binding domain with the
      cholera toxin A2 domain, coexpressed with the cholera toxin B subunit, as an
      intranasal vaccine to prevent experimental urinary tract infection by Proteus
      mirabilis.
AB  - This is a follow-up to our previous study using an intranasal vaccine composed of
      MrpH, the tip adhesin of the MR/P fimbria, and cholera toxin to prevent urinary
      tract infection by Proteus mirabilis (X. Li, C. V. Lockatell, D. E. Johnson, M.
      C. Lane, J. W. Warren, and H. L. Mobley, Infect. Immun. 72:66-75, 2004). Here, we
      have expressed a cholera toxin-like chimera in which the MrpH adhesin-binding
      domain (residues 23 to 157) replaces the cholera toxin A1 ADP-ribosyltransferase
      domain. This chimera, when administered intranasally without additional adjuvant,
      is sufficient to induce protective immunity in mice.

PMID- 15557657
TI  - Expression of a beta-defensin mRNA, lingual antimicrobial peptide, in bovine
      mammary epithelial tissue is induced by mastitis.
AB  - The expression of a beta-defensin, the lingual antimicrobial peptide (LAP), in
      response to mastitis was investigated by real-time PCR of RNA from mastitic and
      control udder quarters. There was a positive relationship between somatic cell
      count in milk and LAP expression. In situ hybridization showed that LAP mRNA was
      expressed in epithelial cells of mastitic tissue. These results suggest that LAP
      plays a role in the innate immune response to mastitis.

PMID- 15557658
TI  - In vitro model of Bartonella henselae-induced angiogenesis.
AB  - Bartonella henselae is a gram-negative pathogen that causes angiogenesis. Here, I
      establish in vitro models to study Bartonella-induced blood vessel formation. I
      found that B. henselae induces long-term endothelial survival and tubular
      differentiation within type I collagen matrix.

PMID- 15557659
TI  - Oral vaccination with recombinant Yersinia enterocolitica expressing hybrid type
      III proteins protects gerbils from amebic liver abscess.
AB  - Protection against invasive amebiasis was achieved in the gerbil model for amebic
      liver abscess by oral immunization with live attenuated Yersinia enterocolitica
      expressing the Entamoeba histolytica galactose-inhibitable lectin that has been
      fused to the Yersinia outer protein E (YopE). Protection was dependent on the
      presence of the YopE translocation domain but was independent from the antibody
      response to the ameba lectin.

PMID- 15557660
TI  - Bacteriophage MAV1 is not associated with virulence of Mycoplasma arthritidis.
AB  - Previous studies demonstrated that Mycoplasma arthritidis strain 158 acquired a
      high degree of virulence upon lysogenization with bacteriophage MAV1. In the
      present study, the association between MAV1 and virulence was reexamined by
      creating new lysogens of 158 and of a relatively avirulent mutant, strain 158-1.
      In the absence of lysogenization, 158 was more virulent than expected. The
      virulence of 158 and 158-1 did not increase upon lysogenization. A major
      antigenic difference between 158 and 158-1 was identified that is unrelated to
      MAV1 and could account for the difference in virulence.

PMID- 15557661
TI  - Two tonB systems function in iron transport in Vibrio anguillarum, but only one
      is essential for virulence.
AB  - We have identified two functional tonB systems in the marine fish pathogen Vibrio
      anguillarum, tonB1 and tonB2. Each of the tonB genes is transcribed in an operon
      with the cognate exbB and exbD genes in response to iron limitation. Only tonB2
      is essential for transport of ferric anguibactin and virulence.

PMID- 15557662
TI  - The calcineurin target, Crz1, functions in azole tolerance but is not required
      for virulence of Candida albicans.
AB  - In Candida albicans, calcineurin is essential for virulence and survival during
      membrane perturbation by azoles. Crz1 is a proposed downstream target of
      calcineurin based on studies of Saccharomyces cerevisiae. However, the in vitro
      phenotypes of C. albicans crz1/crz1 and calcineurin mutants differ and Crz1 is
      not required for virulence.

PMID- 15557663
TI  - Evaluation of the role of constitutive isocitrate lyase activity in Yersinia
      pestis infection of the flea vector and mammalian host.
AB  - Yersinia pestis, unlike the closely related Yersinia pseudotuberculosis,
      constitutively produces isocitrate lyase (ICL). Here we show that the Y. pestis
      aceA homologue encodes ICL and is required for growth on acetate but not for flea
      infection or virulence in mice. Thus, deregulation of the glyoxylate pathway does
      not underlie the recent adaptation of Y. pestis to arthropod-borne transmission.

PMID- 15557664
TI  - Pigeon-associated strains of Salmonella enterica serovar Typhimurium phage type
      DT2 have genomic rearrangements at rRNA operons.
AB  - Strains from a subgroup of Salmonella enterica serovar Typhimurium frequently
      associated with pigeon infections were tested for genomic anomalies and virulence
      in mice. Some strains have a genomic inversion between rrn operons. Two prophages
      found in the common laboratory strain LT2 were absent. Pigeon-associated strains
      are still virulent in mice.

PMID- 15557665
TI  - Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails
      to prevent growth and dissemination of Streptococcus pyogenes in a murine skin
      infection model.
AB  - Fibronectin binding protein F1 (Sfb1) of Streptococcus pyogenes (group A
      streptococcus [GAS]) is a well-characterized adhesin that has been shown to
      induce protection in mice against a lethal intranasal GAS challenge after
      intranasal immunization with cholera toxin B subunit (CTB) as adjuvant. With a
      murine skin infection model, we have shown that Sfb1/CTB vaccination neither
      elicits opsonizing antibodies nor prevents systemic bacterial growth and
      dissemination to internal organs after a subcutaneous GAS challenge. These
      results indicate that an Sfb1-based vaccine should be complemented with
      additional protective antigens in order to be used in areas such as the tropical
      north of Australia, where the skin is the primary route of entry for invasive
      streptococcal diseases.

PMID- 15557666
TI  - Acellular pertussis vaccines and complement killing of Bordetella pertussis.
AB  - Antibody-dependent complement killing of Bordetella pertussis after immunization
      with a three-component acellular pertussis vaccine was characterized.
      Postimmunization activity was unchanged for about half of the adult vaccine
      recipients. The responses of the other individuals were complex, with evidence of
      both beneficial and antagonistic responses occurring, sometimes in the same
      individual.

PMID- 15557667
TI  - Cytokine and fibrogenic gene expression in the conjunctivas of subjects from a
      Gambian community where trachoma is endemic.
AB  - The role of immunity in blinding trachoma is unclear. Conjunctival gene
      expression was measured in a population where trachoma is endemic.
      Proinflammatory (tumor necrosis factor alpha and interleukin-1beta [IL-1beta]),
      anti-inflammatory (IL-10), and fibrogenic (matrix metalloprotease 9) gene
      expression was increased in active trachoma. Markers indicative of T-cell
      response (gamma interferon, IL-4, IL-12p40, and perforin) were increased when
      chlamydial infection was present.

PMID- 15557668
TI  - Effect of inactivation of the HtrA-like serine protease DegQ on the virulence of
      Salmonella enterica serovar Typhimurium in mice.
AB  - DegQ is a serine protease that is highly homologous to HtrA, an important
      virulence determinant of Salmonella enterica serovar Typhimurium. We examined if
      DegQ is involved in serovar Typhimurium pathogenesis. A serovar Typhimurium degQ
      mutant was as virulent as the wild-type strain in mice. However, a serovar
      Typhimurium htrA degQ mutant survived less well in murine organs, particularly in
      the liver, than a serovar Typhimurium htrA mutant. DegQ is not essential for
      serovar Typhimurium pathogenesis but may play a small role during salmonella
      growth at systemic sites.

PMID- 15557669
TI  - Anaplasma marginale major surface protein 2 CD4+-T-cell epitopes are evenly
      distributed in conserved and hypervariable regions (HVR), whereas linear B-cell
      epitopes are predominantly located in the HVR.
AB  - Organisms in the genus Anaplasma express an immunodominant major surface protein
      2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly
      conserved regions. Throughout Anaplasma marginale infection, recombination
      results in the sequential appearance of novel MSP2 variants and subsequent
      control of rickettsemia by the immune response, leading to persistent infection.
      To determine whether immune evasion and selection for variant organisms is
      associated with a predominant response against HVR epitopes, T-cell and linear B
      cell epitopes were localized by measuring peripheral blood gamma interferon
      secreting cells, proliferation, and antibody binding to 27 overlapping peptides
      spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4(+) T-cell
      epitopes eliciting responses of similar magnitude were found in conserved and
      hypervariable regions. T-cell epitope clusters recognized by the majority of
      animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved
      regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were
      concentrated in the HVR, residing within hydrophilic sequences. The pattern of
      recognition of epitope clusters by T cells and of HVR epitopes by B cells is
      consistent with the influence of protein structure on epitope recognition.

PMID- 15557670
TI  - Lipid raft-mediated entry is not required for Chlamydia trachomatis infection of
      cultured epithelial cells.
AB  - Using pharmacologic and biochemical criteria, we evaluated whether uptake of four
      different Chlamydia trachomatis serovars, D, E, K, and L2, was dependent upon
      lipid rafts. Our data suggest that lipid raft-mediated entry is not required for
      C. trachomatis infection of cultured epithelial cells.

PMID- 15557671
TI  - Listeria monocytogenes sigmaB contributes to invasion of human intestinal
      epithelial cells.
AB  - The role of sigma(B) in Listeria monocytogenes infection of human intestinal
      epithelial cells was investigated. Invasion defects associated with loss of
      sigma(B) paralleled those of a DeltainlA strain independently of the sigma(B)
      dependent P2(prfA) promoter. Concomitantly, amounts of inlA transcript and InlA
      protein were significantly decreased in the DeltasigB strain.

PMID- 15557672
TI  - Quality of life in hypertension: the SF-12 compared to the SF-36.
AB  - BACKGROUND: The SF-36 has frequently been used to measure health related quality
      of life (HRQOL) in hypertension. Recently, the SF-12, a shorter form of the SF
      36, has been proposed. However, the validity of the SF-12 in hypertension has not
      yet been assessed. OBJECTIVES: To determine the extent to which the SF-12
      provides similar measurements of HRQOL to those of the SF-36 in hypertensive
      individuals. METHODS: A study assessing the impact of a pharmacy-based
      intervention program on hypertensive individuals served as background for this
      study. One hundred and twelve individuals participated in this study. We compared
      the SF-36 with the SF-12 on item scores and summary measures using intraclass
      correlation coefficients (ICC), Pearson correlation coefficients and linear
      regression. RESULTS: The concordance between the SF-12 and the SF-36 on both
      physical (ICC=0.88) and mental (ICC=0.92) component summary scores (PCS and MCS
      respectively) is high and the relationship is linear and positive. Most of the
      variance in the SF-36 PCS (R2=0.78) and MCS (R2=0.85) can be explained by their
      SF-12 counterparts. The SF-12 PCS and MCS are the only significant predictor
      variables for the corresponding measure of the SF-36. CONCLUSIONS: The SF-12
      appears to be a valid alternative to the SF-36 for clinical practice or research
      purposes when studying hypertensive individuals and their treatment.

PMID- 15557673
TI  - Risk modification for diabetic patients. Are other risk factors treated as
      diligently as glycemia?
AB  - BACKGROUND: The importance of glucose control is recognized both by patients with
      diabetes and their physicians. However, other preventative interventions, such as
      using medications to manage lipid and blood pressure levels, are underused for
      diabetic patients. OBJECTIVES: To determine whether patients with diligent
      glucose management are more likely to use medications that treat lipids and blood
      pressure. METHODS: Administrative data records were evaluated for all diabetic
      patients aged 65 or older residing in Ontario in 1999 without pre-existing
      coronary artery disease (n=161,553). Measures of diligent glucose management were
      insulin use and frequent capillary glucose testing ((3) 2 per day). Outcomes were
      prescription of a lipid-lowering drug or antihypertensive drug. Using
      multivariate modeling, odds ratios for each diligence measure were determined for
      each outcome, adjusting for age, sex, comorbidities, and other covariates.
      RESULTS: Patients using insulin did not have a clinically important difference in
      lipid-lowering drug use (adjusted odds ratio 0.9, 99% confidence interval 0.9 -
      1.0, P=0.002) or antihypertensive drug use (adjusted odds ratio 1.1, 99%
      confidence interval 1.0 - 1.1, P<0.001) versus non-users. Adjusted odds ratios
      for frequent glucose testing were not significantly different from unity for
      either lipid-lowering or antihypertensive drug use. CONCLUSIONS: Patients who
      required and were capable of diligent glucose management, which is invasive,
      expensive and time-consuming, were no more likely to use medications to control
      lipids or blood pressure. Preventative care for patients with diabetes may be too
      focused on glycemic control, and may be neglecting the management of other
      cardiovascular risk factors.

PMID- 15557674
TI  - Allelic loss at the GPx-1 locus in cancer of the head and neck.
AB  - Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously
      implicated in the risk and development of lung and breast cancer, in part the
      result of allelic loss at the GPx-1 locus. This study examined allelic loss at
      the same locus in squamous cell carcinomas of the head and neck. The frequency of
      a polymorphism at codon 198 resulting in either a leucine or a proline at that
      position was surveyed by comparing 133 DNA samples obtained from head and neck
      tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs
      exhibited fewer pro/leu heterozygotes as compared to DNA obtained from the cancer
      free population. Fewer GPx-1 heterozygotes were verified by determining the
      frequency of highly polymorphic alanine repeat sequences in the same gene. The
      analysis revealed an approximately 42% reduction in heterozygosity in the DNA
      from the tumor samples. In order to assess loss of heterozygosity (LOH) at the
      GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and
      microscopically normal tissues adjacent to the tumor, derived from the same
      patients. These studies indicated LOH at the GPx-1 locus in each of the three
      tumor/normal tissues sample sets examined. Furthermore, LOH in the
      microscopically normal tissues at the tumor margin occurred in two of the three
      sample sets examined. These data implicate GPx-1 in the development of squamous
      cell carcinoma the head and neck and suggest that allelic loss of this gene, or
      one tightly linked to it, is an early event in the development of this type of
      malignancy.

PMID- 15557675
TI  - Reference concentrations of trace elements in urine of the Budapestian
      population.
AB  - Reference values in biological specimens are crucial to estimate the type and
      magnitude of environmental and occupational exposure: Because of its importance
      in the excretion of noxious substances and to the noninvasive mode of its
      collection, urine is a useful specimen for monitoring studies. Thus, the
      concentrations of six trace elements (Al, Co, Mo, Nb, Ni, and Ti) were determined
      in 100 urine samples of the Budapestian population by inductively coupled plasma
      mass spectrometry. The obtained creatinine adjusted concentrations (medians) are
      (in microg/g) 9.9, 0.6, 53.5, 0.4, 1.5, and 8.5 for Al, Co, Mo, Nb, Ni, and Ti,
      respectively.

PMID- 15557676
TI  - Does mercury promote lipid peroxidation? An in vitro study concerning mercury,
      copper, and iron in peroxidation of low-density lipoprotein.
AB  - In order to explore the observed association among mercury, atherosclerosis, and
      coronary heart disease, the effects of mercury, copper, and iron on the
      peroxidation of low-density lipoprotein (LDL) and on the enzymatic activities of
      glutathione peroxidase and myeloperoxidase were investigated in vitro. On the
      basis of our nuclear magnetic resonance (NMR) experiments, we conclude that
      mercury does not promote the direct nonenzymatic peroxidation of LDL, like copper
      and iron. In our enzyme measurements, mercury inhibited slightly myeloperoxidase,
      although not significantly in presence of LDL. Instead, inorganic mercury, but
      not methylmercury chloride, inhibited glutathione peroxidase effectively and
      copper even at 10 micromol/L, below physiological concentrations, doubled the
      inhibition rate. Copper and iron had no direct effect on glutathione peroxidase,
      but they both seem to activate production of HOCl by myeloperoxidase. We conclude
      here that, first, mercury and methylmercury do not promote direct lipid
      peroxidation, but that, second, a simultaneous exposure to high inorganic
      mercury, copper, and iron and low selenium concentrations can lead to a condition
      in which mercury promotes lipid peroxidations. This mechanism provides a
      plausible molecular-level explanation for the observed association between high
      body mercury content and atherosclerosis.

PMID- 15557677
TI  - Compositional changes of the muscular layers of the stomach with aging.
AB  - To elucidate compositional changes of the stomach with aging, the authors
      investigated age-related changes of the elements and relationships among the
      elements in the muscular layers of the pylorus, cardia, lesser curvature, and
      greater curvature by inductively coupled plasma-atomic emission spectrometry.
      After ordinary dissection by medical students, the pylori, cardias, lesser
      curvatures, and greater curvatures were removed from the subjects, consisting of
      19 men and 1 woman, ranging in age from 65 to 95 yr. The muscular layers were
      isolated and the element contents were determined. The calcium content increased
      progressively with aging in the muscular layers of the pylorus, cardia, and
      lesser curvature, whereas it tended to increase in the muscular layer of the
      greater curvature with aging. Regarding sulfur, the content increased
      significantly in the muscular layer of the pylorus with aging, but not
      significantly in the muscular layers of the cardia, lesser curvature, and greater
      curvature with aging. Regarding the relationships among the elements, significant
      direct correlations were found among calcium, phosphorus, sulfur, and magnesium
      in both the muscular layers of the pylori and cardias, with some exceptions.

PMID- 15557678
TI  - Review on the role of dietary zinc in poultry nutrition, immunity, and
      reproduction.
AB  - Zinc is an important nutrient in animal metabolism. In poultry, zinc serves not
      only as a nutrient but can also be used as a dietary supplement to manipulate the
      reproductive system of the bird. This article summarizes the general
      biochemistry, physiology, and nutritional aspects of zinc metabolism to provide a
      brief overview on what is known regarding zinc. The potential role of zinc in
      poultry immune response, Salmonella infection, and molting are emphasized.

PMID- 15557679
TI  - Using a feed-grade zinc propionate to achieve molt induction in laying hens and
      retain postmolt egg production and quality.
AB  - A commercial-feed-grade form of zinc propionate was examined as a potential feed
      amendment at a concentration of 1% zinc to induce molt in 90-wk-old hens. Dietary
      treatments consisted of 4 treatment groups of 28 birds each randomly assigned to
      either (1) molted conventionally by feed withdrawal, (2) 1% zinc as Zn acetate,
      (3) 1% zinc as Zn propionate, or (4) nonmolted control for 9 d. Ovary weights of
      hens fed Zn acetate or Zn propionate were not significantly different from each
      other, but hens fed Zn acetate or Zn propionate were significantly (p<0.05)
      lighter than the ovary weight of nonmolted control hens. Zinc concentrations in
      the kidney and liver were significantly (p<0.05) increased in both Zn acetate-
      and Zn propionate-molted hens when compared to either nonmolted control-fed hens
      or feed-withdrawal molted hens. Over the entire 3-mo postmolt period, there were
      no significant differences in interior or exterior egg qualities among the four
      treatments. Egg production of hens fed Zn acetate was significantly lower than
      feed-withdrawal hens, Zn propionate-fed hens, or nonmolted control hens (p<0.05).
      The data of the current study demonstrated that feeding a feed grade of Zn
      propionate (1% Zn)-supplemented diet can induce molt and retain postmolt egg
      quality and production comparable to hens molted by feed withdrawal.

PMID- 15557680
TI  - Effects of dietary combination of chromium and biotin on egg production, serum
      metabolites, and egg yolk mineral and cholesterol concentrations in heat
      distressed laying quails.
AB  - Chromium picolinate is used in the poultry diet because of its antistress effects
      in addition to the fact that the requirement for it is increased during stress.
      This study was conducted to determine if the negative effects of high ambient
      temperature (34 degrees C) on egg production, egg quality, antioxidant status,
      and cholesterol and mineral content of egg yolk could be alleviated by
      combination of chromium picolinate and biotin (0.6/2.0; Diachrome, as formulated
      by Nutrition 21 Inc.), in laying Japanese quails (Coturnix coturnix japanica).
      Quails (n= 240; 50 d old) were divided into 8 groups, 30 birds per group. The
      quails were fed either a basal diet or the basal diet supplemented with 2, 4, or
      8 mg of Diachrome/kg diet. Birds were kept at 22 degrees C and 53% relative
      humidity (RH). At 14 wk of age, the thermoneutral (TN) group remained in the same
      temperature as at the beginning of experiment, whereas the heat stress (HS) group
      was kept in an environment-controlled room (34 degrees C and 41% RH) for 3 wk.
      Heat exposure decreased performance when the basal diet was fed (p = 0.001).
      Diachrome supplementation at 4 and 8 mg/kg diet, increased feed intake (p =
      0.05), egg production (p = 0.05), feed efficiency (p = 0.01), egg weight (p =
      0.05), and Haugh unit (p = 0.01) in quails reared under heat stress conditions.
      Heat exposure increased concentrations of serum malondialdehyde (MDA) (p =
      0.001), glucose, and cholesterol (p = 0.01), which were elevated by supplemental
      Diachrome (p < or = 0.05). Egg yolk Cr, Zn, and Fe (p = 0.01) concentrations
      increased linearly, whereas MDA and cholesterol concentrations decreased (p =
      0.05) as dietary Diachrome supplementation increased in HS groups. Similar
      effects of supplementation on serum levels of glucose and cholesterol (p = 0.05)
      and egg yolk concentrations of cholesterol (p = 0.05) and Cr (p = 0.01) were
      observed in TN groups. No significant differences in other values were observed
      in the TN groups. Results of the present study suggest that supplementation with
      Diachrome protects the quail by reducing the negative effects of heat stress.

PMID- 15557681
TI  - Correlation of neuropathy with corneal sensitivity and lacrimal gland secretion
      in type 2 diabetes mellitus patient.
AB  - AIM: To evaluate correlation between blood glucose control, corneal sensitivity
      and lacrimal secretion in type 2 DM with peripheral neuropathy. METHODS: A cross
      sectional study has been conducted in 20 type DM with peripheral neuropathy and
      20 without peripheral neuropathy at the Department of Internal Medicine and
      Ophthalmology, Ciptomangunkusumo Hospital, Faculty of Medicine University of
      Indonesia, from August through November 2002. All subject underwent a
      comprehensive medical examination, including esthesiometer Semmes-Weinstein 10 g,
      HbA1c, Schirmer test, and corneal sensitivity measurements. RESULTS: The mean
      corneal sensitivity was significantly lower in diabetic patients with neuropathy
      (p=0.000). HbA1(c) was related to corneal sensitivity (p=0.016). CONCLUSION: In
      type 2 DM with peripheral neuropathy, corneal sensitivity was demonstrated to be
      significantly decrease, all of which seems to be due to the status of blood
      glucose control.

PMID- 15557682
TI  - The influence of calorie restriction during the Ramadan fast on serum
      fructosamine and the formation of beta hydroxybutirate in type 2 diabetes
      mellitus patients.
AB  - AIM: To determine whether the Ramadan fasting can improve metabolic control
      evaluated from serum fructosamine and beta hydroxybutirate in patients with Type
      2 diabetes mellitus. METHODS: This was a prospective one group before and after
      study (self-controlled study). Twenty four patients from the outpatient clinic of
      the Metabolic Endocrinology Division of the Department of Internal Medicine,
      Faculty of Medicine, University of Indonesia/ Cipto Mangunkusumo General Hospital
      who were well under control underwent assessment for serum fructosamine at weeks 
      1, 4, and 6 (2 weeks after the Ramadan fast) and beta hydroxybutirate formation
      at week 4. RESULTS: The mean serum fructosamine on weeks -1, 4, and 6 were 334.2
      +/-45.7; 303.9 +/-34.5 dan 313.6 +/-45.9 umol/L. The beta hydroxybutirate level
      was 0.3 mmol/L. CONCLUSION: The Ramadan fasting in patients with well-controlled
      and medium-controlled type 2 diabetes mellitus could cause a reduction in serum
      fructosamine and does not cause formation of beta hyroxybutirate.

PMID- 15557683
TI  - The efficacy of repaglinide monotherapy and in combination with metformin in
      Indonesian type 2 diabetes mellitus patients.
AB  - AIM: To investigate the efficacy and safety of repaglinide alone and in
      combination with metformin therapy. METHODS: Seventy-two type 2 diabetes patients
      who were oral anti-diabetic drugs (OAD)-naive or currently on OAD for </=36
      months with HbA1c </=9% and fasting plasma glucose (FPG) pound 13 mmol/L were
      recruited. Patients were titrated for 6 weeks to a dose level which maintained
      fasting blood glucose at 4.4-7.0 mmol/L and continued treatment for 8 weeks. Dose
      regimen started with 0.5 mg repaglinide each main meal, progressing to 1.0 mg
      repaglinide, 1.0 mg repaglinide + metformin 500 mg b.i.d. and 1.0 mg repaglinide
      + metformin 500 mg t.i.d., depending on patients' glycaemic status. Patients'
      glycaemic control (HbA(1c) and FPG), body weight and other safety parameters were
      evaluated. RESULTS: Thirty-seven patients completed the trial. Patients were
      overweight (mean BMI 25.5 +/- 4.1 kg/m(2)) with mean age 52.5 +/- 8.8 years and
      mean diabetes duration of 2.4 +/- 3.8 years. Mean HbA1c (2.26 +/- 0.22%, [p
      <0.05]) and FPG (3.31 +/- 0.47 mmol/L, [p <0.05]) decreased significantly from
      baseline. Body weight did not change significantly (0.85 +/-0.45 kg, p=0.068). Of
      the 33 patients who had baseline FPG >7.0 mmol/L, it appeared that repaglinide
      alone at doses 0.5 or 1.0 mg achieved FBG <7.0 mmol/L in 67% of patients. The
      majority of the treatment emergent adverse events were mild and unlikely related
      to trial product. Episodes of symptomatic hypoglycaemia were low (9.3%) in
      frequency. The changes in haematology, clinical biochemistry and urinalysis were
      mostly minor or remained unchanged. Vital signs and the results of physical
      examination also remained unchanged. Three of the four withdrawals were due to
      adverse events but were unlikely related to trial product. CONCLUSION: treatment
      with repaglinide alone and in combination with metformin was efficacious in
      glycaemic control in OAD-naive or previous users. Most of the patients appeared
      to achieve good control with repaglinide alone. The treatment regimens were safe
      (317 words).

PMID- 15557684
TI  - Renal involvement in leptospirosis at Dr. Cipto Mangunkusumo and Persahabatan
      Hospitals.
AB  - AIM: To describe clinical pattern of ARF caused by leptospirosis and its related
      factors. METHODS: A cross-sectional study using medical record data of all
      leptospirosis cases admitted to Cipto Mangunkusumo and Persahabatan General
      Hospitals between January 1993 and December 1996. Patient identification included
      age, sex, and occupation. Clinical symptoms were described in details and
      followed by laboratory testing i.e. peripheral blood count, urinalysis, blood
      urea and creatinine, liver function test, and pancreatic enzymes assay. RESULTS:
      Seventy-five percent were men and the mean age was 38.3 years old. Sixty out of
      68 (88.2%) patients had ARF as defined by an increase of plasma creatinine level
      of >1.5 mg/mL. The most common presenting symptoms in patients with ARF were
      fever (100%), nausea and vomiting (95.0%), muscle pain (88.1%) and jaundice
      (71.3%). The mean duration of fever 7.2 days. The most frequent laboratory
      abnormalities were increased erythrocyte sedimentation rate (100%), leukocytosis
      (90%) and increase total bilirubin level (87.5%). Only leukocytosis showed a
      significant difference between ARF and non-ARF patients (p=0,014). Leptospira
      bataviae was found in 95.6% of patients and 96.7% of ARF patients. Penicillin was
      given to 80.9% of patients with only 2 (2.9%) deaths. CONCLUSION: Although
      significant correlation cannot be established, we concluded that nausea,
      vomiting, muscle pain, jaundice, increased ESR and total bilirubin level should
      alert the physician about the possibility of renal involvement in leptospirosis
      patients with prolonged fever. Leptospira bataviae was an important virulent
      pathogen. Treatment with penicillin may significantly improve organ failure and
      was considered the drug of choice in managing leptospiral infection.

PMID- 15557685
TI  - Sepsis and acute respiratory distress syndrome in alcoholic ketoacidosis.

PMID- 15557686
TI  - Spontaneous rupture of hepatocellular carcinoma in patients with cirrhosis of the
      liver.

PMID- 15557687
TI  - The role of phytosterols as cholesterol lowering agents.

PMID- 15557688
TI  - Disregulation process of cancer cell proliferation.

PMID- 15557689
TI  - The role of low molecular weight heparin (LMWH) in acute thrombosis (stroke and
      acute coronary syndrome).

PMID- 15557690
TI  - Deep vein thrombosis.

PMID- 15557691
TI  - Renal transplantation problem in Indonesia.

PMID- 15557692
TI  - Consensus of Malaria Management 2003 (part 2).

PMID- 15557693
TI  - [Molecular cytogenetic techniques and their application in clinical diagnosis].
AB  - Cytogenetics analysis is at present the basic element of the diagnostic process
      of genetic disorders which are caused by chromosomal abnormalities. Since the
      chromosome banding technique has been introduced in the 1970s, it has been
      available as a diagnostic tool of a number of clinical syndromes. It enabled to
      prove the causal association between specific chromosomal abnormalities and
      clinical features observed in patients. However, since banding resolution is not
      always sufficient for the identification of chromosomal abnormalities, additional
      techniques for solving diagnostic dilemma of classical cytogenetics are needed. A
      new field of cytogenetics -- molecular cytogenetics, the product of a combination
      of cytogenetics and molecular biology, has increased the resolution and
      diagnostic utility of cytogenetic analysis. The basic method of molecular
      cytogenetics is fluorescence in situ hybridization (FISH). It enables a specific
      detection of unique sequences, chromosomal regions or entire chromosomes in
      metaphase, interphase cells or in tissue sections. In this article FISH technique
      and its modifications such as multicolor FISH (M-FISH, SKY, CCK), Primed In Situ
      Labelling (PRINS) and Comparative Genomic Hybridization (CGH) are presented. The
      range of applications and the use of these techniques for the identification of
      chromosomal abnormalities in relation to diagnostic possibilities of the
      classical methods of karyotyping is also discussed.

PMID- 15557694
TI  - [Treatment progress of Duchenne Muscular Dystrophy (DMD)].
AB  - Duchenne muscular dystrophy (DMD) is a common lethal disease for which no
      effective treatment is currently available. There exists a mouse model of the
      disease in which the usefulness of gene therapy was established. However, no
      progress towards human application was made due to the lack of a proper method
      for gene delivery. During the past several years, researchers acquired data which
      led them to believe that bone marrow stem cells are capable of generating not
      only blood cells, but also liver, heart, skin, muscle, and other tissue. Although
      the term "stem cell plasticity" became very popular, other studies have suggested
      that bone marrow might contain different types of stem cells that can produce non
      hematopoietic cells. For example, mesenchymal stem cell (MSC) in bone marrow give
      rise to osteocytes, chondrocytes, adipocytes, and skeletal muscle. Recently,
      researchers have been able to show that transplanted bone marrow cells can
      contribute to muscle cells in a human patient who was diagnosed with two genetic
      diseases: severe combined immunodeficiency (SCID) and Duchenne muscular
      dystrophy. The odds of this happening is estimated at one in seven million. The
      results of studying this patient's medical history were reported by collaborating
      researchers at Children's Hospital, Los Angeles and Children's Hospital, Boston
      in an article titled "Long-term persistence of donor nuclei in a Duchenne
      muscular dystrophy (DMD) patient receiving bone marrow transplantation" published
      in the September 2002 issue of the Journal of Clinical Investigation. This
      patient was transplanted 15 years ago at Children's Hospital Los Angeles with
      paternal HLA-haploidentical T cell-depleted bone marrow. He engrafted and became
      a hematopoietic chimera having T and NK lymphocytes of donor origin. Studies
      performed on the muscle biopsy from the patient 13 years after transplantation
      demonstrated that the muscle showed evidence of donor derived nuclei. In
      addition, analysis of his bone marrow showed that small numbers of MSC were also
      derived from the transplanted bone marrow. Unfortunately, there was no evidence
      that the number of new muscle cells from the donor was able to decrease the
      progression of his muscular dystrophy. The revelation of finding the donor's
      cells in the muscle of the patient provides new hope for patients with the same
      disease. In the future it may be possible for mesenchymal cells to be isolated,
      ex vivo expanded and transplanted into patients with muscle diseases.

PMID- 15557695
TI  - [Interleukin 13 and 18 serum concentration in children with cow milk
      hypersensitivity].
AB  - The aim of the study was the estimation of IL-13 and IL-18 concentration in serum
      of children with cow milk hypersensitivity and estimation of its usefulness in
      clinical practice. MATERIAL AND METHODS: 30 children (14 boys, 16 girls) at the
      age 6-24 months, average 10.5 months. The children were divided into two groups.
      Group 1 included 18 children with elevated total IgE, group II, 12 children with
      normal IgE. In all children with suspected cow milk hypersensitivity, a diet
      based on strong milk hydrolysates or soy-milk formulas was advised. In 10
      children IL-13 and IL-18 were examined three times: at the moment of diagnosis
      and after 3 and 6 months of dietary treatment. In 20 children IL-13 and IL-18
      were estimated twice. Total IgE and specific IgE were performed by HYTER 288; IL
      13 and IL-18 were measured by Bender Med System. The results were analysed
      statistically. RESULTS: in children with elevated IgE statistically significant
      higher IL-13 concentration was found and the mean IL-18 concentration in this
      group was lower but the difference was not statistically significant. We
      confirmed a positive correlation between elevated IgE and IL-13 concentration and
      a negative correlation between IgE and IL-18 before introducing the diet. In
      children with clinical improvement there was a nonsignificant decrease of IL-13
      and increase of IL-18 concentration after diet introduction. In the group without
      clinical improvement, high IL-13 and low IL-18 concentration during diet were
      observed (p < 0,01). Highly positive correlation between serum IL-18 after 3
      months of elimination diet and clinical improvement was observed. Highly negative
      correlation between mean IL-13 concentration after 6 months of diet and the
      clinical condition were observed. CONCLUSIONS: The correlation between IL-13
      concentration and elevated IgE, indicates a connection of this cytokine with
      atopy. Negative correlation between IL-18 concentration and elevated IgE suggests
      a possibility of inhibiting IgE synthesis by this cytokine. A strong correlation
      between IL-18 concentration and clinical improvement after 3 months of
      elimination diet may imply a reduction of the allergic process. High negative
      correlation between IL-13 concentration and clinical improvement after 6 months
      of elimination diet may indicate a prolongation of the allergic process.

PMID- 15557696
TI  - [Usefulness of selected serum cytokines for monitoring compliance with a gluten
      free diet in celiac patients].
AB  - In celiac disease in response to gluten, the immune reaction develops both in the
      small intestine and in cells of peripheral blood. The profile of cytokines
      produced by the cells differs between patients in compliance and not, with regard
      to gluten-free diet. THE AIM: The aim of the study was to evaluate the usefulness
      of serum profile determination for chosen cytokines in monitoring of gluten-free
      diet in celiac patients. MATERIAL AND METHODS: The investigation comprised a
      group of 110 patients with celiac disease, who were divided into two groups: with
      active form of celiac disease (EmA(+), n=56) and with a non-active form of the
      disease (EmA (-), n = 54). The chosen cytokine IL-2, IL-4, IL-6, IL-IO and IFN-y
      levels were determined in patients and soluble receptor For IL-2 (sIL-2R). For
      determination of the selected cytokines, brand sets of ELISA microplates (Bender
      Med. Systems) were used according to recommendations of the producer. The
      obtained results were analysed with statistical methods. RESULTS: Comparison of
      mean values of chosen cytokines levels in particular groups showed, that in case
      of sIL-2R and IL-6, they were significantly statistically higher in the group of
      patients complying to gluten-free diet. Statistical analysis revealed negative
      correlation between sIL-2R levels and the length of diet compliance in patients
      with non-active celiac disease and positive correlation between concentrations of
      sIL-2R and the titre of endomysial antibodies in the group of patients with
      active form of the disease. CONCLUSIONS: The determination of sIL-2R levels in
      serum together with endomysial antibodies assessment can be used as a method for
      monitoring the compliance to gluten-free diet in patients with celiac disease.

PMID- 15557697
TI  - [Normal and abnormal height and weight development in children and adolescents in
      Krakow--changes and trends in the last thirty years].
AB  - The aim of this study is to determine the frequency of height and weight
      disharmony in children and adolescents in Krakow, i.e. both overweight and
      underweight in relation to height and the trends in last thirty years. MATERIALS
      AND METHODS: 4532 individuals -- a random sample of children and adolescents
      (2416 boys and 2107 girls) were examined in 2000. The results of the examination
      were compared with data obtain in 1971 (random sample of 4090 individuals) and
      with results from 1983 (random sample of 6536 individuals). Percentile position
      of height and weight were compared: the difference of two or more percentiles
      channels classified the results as overweight or underweight depending on height.
      THE RESULTS: Of the research prove that the frequency of occurrence of dis
      harmonious body built increases with age, both with regard to overweight and
      underweight related to height and this phenomenon is more frequent in girls. In
      last thirty years a progressive increase of frequency of overweight was observed,
      but in girls it was noticeable and statistically significant only in 1971 --
      1983.

PMID- 15557698
TI  - [Influence of chronic HBV infection and interferon therapy on somatic development
      of children].
AB  - Interferon alpha (IFN) is the most common treatment in chronic hepatitis B in
      children. Its impact on the development of children is still discussed. AIM OF
      THIS STUDY: The assessment of body mass and body height of children after
      interferon therapy and the influence of chronic HBV infection on these
      parameters. MATERIALS AND METHODS: The study concerned 64 children who suffered
      chronic hepatitis B. Among them 36 boys and 12 girls were treated with interferon
      alpha and 18 boys and 4 girls not treated. They were compared with a control
      group (416 boys and 457 girls). Scatter plots and chi-square test were used in
      analysis. RESULTS: Treated and not treated children were found in 3 distinguish
      zones: middle zone M+/- 1/2 SD, above and below it. Body mass: in the middle zone
      about 30% boys and 25% girls were found. In the high zone 20% boys and 40% girls.
      In low zone 45% boys and 30% girls. Body height: in the middle zone there were
      30% boys as well as 40% girls. In high zone 35% boys and 30% girls. In low zone
      30% boys and 25% girls were found. The comparison of frequency of treated and not
      treated children represented in the three zones was not statistically
      significant. Among sick children (treated and not treated together) about 60%
      boys and about 43% girls were characterized by lower weight than arithmetic mean
      of a population study. According to height about 40% boys and about 37% girls
      were found to be under mean of control group. CONCLUSIONS: 1. Interferon alpha
      can be used in chronic hepatitis B in children as a drug which does not cause
      permanent disturbances of body mass and body height 2. Children with chronic
      hepatitis B infection must be treated early to stop growth retardation.

PMID- 15557699
TI  - [Comparison of the rate of body weight increase in children fed with cow's milk
      formulas and children with alimentary sensitivity, fed with milk-replacing
      mixtures].
AB  - PURPOSE: The aim of this study was a comparison of body weight increase rate in
      two groups of children up to 18 months of age. The first group was fed with cow s
      milk formula. The second group due to allergy or cow milk intolerance was fed
      with milk-replacing mixtures: hydrolyzates with higher rate of protein hydrolysis
      or soya preparations. PATIENTS AND METHOD: In the analysed group of 332 children,
      135 children were fed with cow's milk formulas, 142 children were given no-milk
      diet based on protein hydrolyzates and another 55 were fed with soya mixtures.
      The average body weight increase values were analysed in three months periods of
      half-years of life and in relation to gender and type of feeding. The obtained
      results were analysed statistically. RESULTS: There were statistically
      significant greater mean monthly increments of body weight in male children fed
      with cow's milk formulas as compared to male children fed with hydrolyzates in
      the first quarter and in the first half-year of life and male infants fed with
      soya mixtures. In subsequent three and six months periods no statistically
      significant differences in mean monthly values of body weight increase in
      relation to type of nutrition were found.

PMID- 15557700
TI  - [Long term analysis of chronic gastritis with Helicobacter pylori infection in
      children and teenagers with chronic abdominal pain].
AB  - INTRODUCTION: Helicobacter pylori can be the cause of chronic gastritis and
      gastric ulcer. In children, the infection can be asymptomatic or can be a cause
      of dyspepsia. THE AIM of the study was to evaluate the incidence of chronic
      gastritis and H. pylori infection in children and teenagers investigated because
      of chronic abdominal pain. MATERIAL AND METHODS: From the group of 3762 children
      and teenagers investigated during 10 years in the Department of Children's
      Disease, Allergology and Gastroenterology University Medical School in Bydgoszcz,
      because of abdominal pain, we selected 910 patients (24.2%) with chronic
      gastritis and coexisting H. pylori infection. RESULTS: We discovered that the
      highest number of infected children was in the age group 7-14 years (75.8%) then
      15-18 (13.2%), 3-6 (10.4 %) and 0-2 (0.6%). The study demonstrated that the
      number of infected girls (57%) was higher than the number of infected boys.
      CONCLUSION: In our investigations chronic gastritis with H. pylori infection in
      children and teenagers diagnosed because of abdominal pain, occurs in about 25%
      of patients and this fact should be considered in diagnostic procedures and
      management.

PMID- 15557701
TI  - [Environmental factors in the etiopathology of inflammatory bowel syndrome].
AB  - Inflammatory bowel syndrome (IBS) mainly includes ulcerative colitis (UC) and
      Crohn's disease (CD). UC and CD are chronic and recurrent conditions, with a
      tendency to exacerbations and remissions. The incidence of diseases worldwide has
      increased over the last years. Although the etiology of inflammatory bowel
      syndrome has been studied intensively it still remains unclear. The development
      and persistence of inflammation is an effect of numerous factors: proinflammatory
      (aggressive), regulating bowel mucosa homeostasis and protective factors.
      Proinflammatory factors include intestinal bacteria, bile acids, digestive
      enzymes, lipopolysaccharides and peptidoglycans. Protective mechanisms are
      impermeability of mucosa barrier, presence of intestinal mucus, activity of
      secretive immunoglobulins, some prostaglandins and interleukins, glutamine,
      somatostatin, cortisol and short-chain fatty acids. Factors modifying intestinal
      mucosa homeostasis consist of genetically determined immunoregulators and
      activity of intestinal mucosa barrier and some environmental factors (diet,
      smoking, infections, stress, antibiotics and others). Environmental factors are
      jointly responsible for IBS occurrence in case of genetically determined
      dysregulation leading to proinflammatory cytokines overproduction or disturbances
      in synthesis of cytokines regulating intestinal mucosa homeostasis.

PMID- 15557702
TI  - [Von Willebrand factor and thrombomodulin as markers of endothelial cell
      functions in children with chronic viral hepatitis].
AB  - INTRODUCTION: Vascular endothelial cells play an important role in haemostasis.
      Similar to hepatocytes they synthesise many substances taking part in blood
      clotting and fibrinolysis. OBJECTIVE: The aim of the study was the evaluation of
      markers of endothelial cells: von Willebrand factor (vWf) and thrombomodulin (TM)
      in children with chronic viral hepatitis. MATERIAL AND METHODS: VWf and TM levels
      were measured using ELISA method. The examined group consists of 105 children
      with chronic viral hepatitis aged 2 to 18 years. RESULTS: The concentrations of
      vWf and TM were significantly higher in chronic viral hepatitis compared to
      controls. The values of TM were higher in chronic viral hepatitis B in comparison
      to hepatitis C and higher in boys than in girls. The markers of endothelial cells
      do not depend on the degree of inflammation and fibrosis. CONCLUSION: Increased
      levels of vWf and TM suggest stimulation of endothelial cells in children with
      chronic viral hepatitis B and C.

PMID- 15557703
TI  - [Neonatal vitamin D status and calcium-phosphorus homeostasis in the third week
      of life].
AB  - AIM: Assessment of vitamin D status and calcium -phosphorus homeostasis in term
      newborns before routine supplementation. MATERIAL AND METHOD: Calcidiol (25OHD),
      calcium, phosphorus and alkaline phosphatase in serum and Ca (urine)/creatinine
      (urine) ratio (mg/mg), P (urine)/creatinine (urine) ratio (mg/mg) and tubular
      phosphate reabsorption rate (TRP= [1-(P(urine) / P(serum). creatinine
      serum/urine)].100%) in 3rd week of life in 56 appropriate for gestational age
      term neonates was measured. First group contains 35 newborns (62.5%) with normal
      25OHD values and second group 21 newborns (37.5%) with hypovitaminosis D (25OHD <
      11 ng/ml). RESULT: Mean 25OHD concentration was 15.23 ng/ml + 8.57 ng/ml.
      Maternal vitamin D supplementation (10 ug/day) for more than 4 months of
      pregnancy was similar in both groups (55.9% vs. 52.4%) (p>0.05). There were
      51.43% breastfed newborns in group one and 85.71% in group two (p=0.009). Median
      25OHD concentration in breastfed newborns was 11.2 ng/ml and 18.5 ng/ml in
      formula fed babies (p=0.017). There were no statistical differences between
      groups in calcium (2.44 vs. 2.41 mmol/l), phosphorus (2.27 vs. 2.22 mmol/l) and
      alkaline phosphatase (261 vs. 266 U/L) blood concentration and Ca
      (urine)/creatinine (urine) ratio (0,34 vs. 0,25mg/mg) and TRP (86% vs. 88%)
      (p>0.05). The P (urine) /creatinine (urine) ratio in the first group was 2.3mg/mg
      and 1.42 mg/mg in the second group (p=0.048). CONCLUSIONS: Neonatal vitamin D
      stores in the 3rd week of life are not more dependent on maternal vitamin D
      supplementation during pregnancy. Breastfed infants are at greater risk of
      hypovitaminosis D than formula fed infants, therefore earlier vitamin D supply
      should be considered. The hypovitaminosis D has no influence on basic parameters
      of Ca-P homeostasis in the 3rd week of life.

PMID- 15557704
TI  - [Takayasu's disease in a 14 years old girl].
AB  - Takayasu's disease is a chronic, nonspecific arteritis of unknown etiology. It
      mainly affects young women in the second and third decade of life. The reports of
      the disease in pediatric patients are rare. The pathological process involves all
      the layers of the arterial wall. It affects primarily the aortic arch and its
      main branches. If the renal arteries are involved, hypertension develops. A 14
      year-old girl suffered from Takayasu's disease was described. The first symptoms:
      tonic-clonic seizures, neurological signs and high arterial blood pressure were
      observed in a previously healthy girl. The diagnostics process was presented with
      special attention given to the interpretation of radiological imagings. The
      diagnosis of Takayasu's disease was based on result of angiography. This
      examination demonstrated the abdominal aorta abnormalities which have been
      described in patients with Takayasu's disease and the right renal artery
      stenosis.

PMID- 15557705
TI  - Atherosclerosis and matrix dystrophy.
AB  - Atherosclerosis is characterized by inflammatory metabolic change with lipid
      accumulation in the artery. Atherosclerotic plaque occurs at discrete locations
      in the arterial system and involves the proliferation of smooth muscle cells
      (SMCs) together with imbalance of the extracellular matrix elements, elastic
      fiber in particular. The role of elastin in arterial development and disease was
      confirmed by generating mice that lack elastin. Thus, elastin is a critical
      regulatory molecule that regulates the phenotypic modulation, proliferation and
      migration of SMCs. We estimated that elastin expression and SMC proliferation are
      coupled inversely: potent stimulators of cell proliferation may potentially
      inhibit elastin expression and potent inhibitors of cell proliferation can
      stimulate elastin expression. Moreover, elastin was found to be expressed
      maximally at the G(0) and minimally at the G(2)/M phase during the cell cycle,
      suggesting that its expression is regulated by the cell growth state. The elastin
      peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin
      expression. The inhibition of elastin expression by elastin fragments may be
      reflected in the negative feedback regulatory mechanism. The relationship between
      cell proliferation and elastin expression may be changed in atherosclerosis.
      Areas of atherosclerotic plaque show abnormality of elasticity and permeability
      from the viewpoint of the physiological function of the arterial wall. The
      etiology was estimated to be that cholesterol and calcium are deposited on the
      elastic fiber, resulting in decreased elastin synthesis and cross-linking
      formation. In addition, these dysfunctions of elastin fiber are also associated,
      in that the down-regulation of elastin and its related components (fibrillin-1
      and lysyl oxidase) are directly related to calcification in SMCs. The denatured
      arterial elastin by cholesterol and calcium accumulation was also susceptible to
      proteolytic enzymes such as elastase and matrix metalloproteinase (MMP).
      Therefore, metabolic change in elastic fiber induces decreased elasticity and is
      associated with essential hypertension. Vitamin K(2) is used in drug therapy
      against atherosclerosis, or calcification in diabetes mellitus or dialysis, due
      to its promotion of the carboxylation of the matrix Gla protein.

PMID- 15557706
TI  - Aging and HDL metabolism in elderly people more than 100 years old.
AB  - Epidemiological studies have enhanced the importance of high-density lipoprotein
      (HDL) as a risk factor for CAD, as well as disability and frailty in the oldest
      elderly. Therefore, HDL and molecules involved in HDL metabolism seem to be
      attractive candidates for longevity-promoting factors. A series of observational
      studies has demonstrated that the predominance of the larger, more lipid-rich
      HDL2 subclass is a reproducible phenotype among centenarians. This finding was
      recently evolved by nuclear magnetic resonance technology in quantification of
      lipoprotein particle size. However, results of investigations into the mechanisms
      underlying the lipoprotein profiles in the oldest elderly have been conflicting.
      Genetic variation in cholesteryl ester transfer protein (CETP), which is a
      carrier protein in reverse cholesterol transport, was demonstrated to have no
      association with longevity in one study, but to have positive impacts on large
      HDL particles and longevity in another. Regarding environmental factors, acute
      phase reactant and nutritional status are frequently associated with HDL-C levels
      in the oldest elderly, however, the causality of the association remains to be
      elucidated. Determination of the association between cognitive function and HDL
      in the oldest elderly is also a future task. To obtain further insight into the
      mechanistic roles of low HDL in the pathophysiology of geriatric syndrome, a much
      greater effort should be invested in this research field.

PMID- 15557707
TI  - Cholesterol-independent effects of statins and new therapeutic targets: ischemic
      stroke and dementia.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      "statins", are used as cholesterol-lowering agents worldwide. Statins inhibit
      cholesterol biosynthesis, leading to enhanced uptake of low-density lipoprotein
      (LDL) from the circulation via LDL receptors. This strong cholesterol-lowering
      action contributes to the beneficial effects of statins. For example, large
      clinical trials have demonstrated that statins significantly reduce
      cardiovascular risk. Recent research has shown that statins have other multiple
      actions involved in endothelial function, cell proliferation, inflammatory
      response, immunological reactions, platelet function, and lipid oxidation. These
      "pleiotropic actions" of statins probably provide a significant contribution to
      the reduction of cardiovascular events. This review summarizes the pleiotropic
      actions of statins in both basic and clinical studies. It also considers the
      potential for statin therapy in the treatment of stroke and dementia.

PMID- 15557708
TI  - Predictors of atherosclerosis.
AB  - It is herein discussed what should be measured as predictors of atherosclerosis,
      to increase the predictive power of coronary risk evaluation in clinical
      practice. Plasma apolipoprotein (apo)B and apoAI have been reported to be
      stronger predictors of coronary artery disease (CAD) than plasma low-density
      lipoprotein (LDL)-cholesterol (C) and high-density lipoprotein (HDL)-C. The
      estimation of plasma levels of remnants of TG-rich lipoproteins is also important
      for coronary risk evaluation. An increase in plasma small, dense LDL is a risk
      factor for CAD. It is not practical to measure plasma small, dense LDL as a
      routine clinical examination. We should estimate the plasma levels of small,
      dense LDL by plasma triglyceride (TG), apoB, and HDL-C levels. Oxidized LDL (ox
      LDL) plays an important role in atherosclerosis. Further large-scale, prospective
      studies are necessary to determine whether the measurement of plasma ox-LDL and
      autoantibodies against ox-LDL is an essential predictor of atherosclerosis. High
      plasma levels of Lp(a) are a risk factor for atherosclerotic vascular diseases in
      subjects with high plasma LDL-C levels and multiple coronary risk factors.
      Metabolic syndrome (MS) has been recognized recently as a predictor of CAD. As a
      result, it should be elucidated whether MS must be involved in the coronary risk
      evaluation score because all components of MS are involved in the score. A high
      plasma level of high-sensitivity C-reactive protein (hs-CRP) is an important
      predictor of atherosclerotic diseases. Whether it is essential to measure the
      plasma levels of atherosclerosis surrogate markers in clinical practice remains
      to be elucidated. It is concluded that plasma levels of apoB, apoAI, remnant-like
      particle (RLP)-C, lipoprotein (a) [Lp(a)], and hs-CRP in addition to those of
      lipids should be measured as predictors of atherosclerosis in clinical practice.
      We need to establish a new atherosclerosis risk evaluation scoring system
      involving the above factors, based on large-scale, prospective studies, to
      prevent atherosclerotic vascular diseases. In Japan, plasma levels of Lp(a), RLP
      C, and hs-CRP are routinely measured in clinical practice. As a result, it would
      be rather easy to establish a new atherosclerosis risk evaluation scoring system
      in Japan.

PMID- 15557709
TI  - Impact of increasing diabetes on coronary artery disease in the past decade.
AB  - We studied the coronary risk factors of hospitalized patients with coronary
      artery disease (CAD) in the Department of Cardiovascular Internal Medicine of
      Kobe University Hospital in 1993, 1996, 1999 and 2003, and examined trends in the
      factors over the past decade. The prevalences of diabetes mellitus (DM) (24.7%,
      33.6%, 41.1% and 44.7%, respectively) and impaired glucose tolerance (IGT) (5.9%,
      8.0%, 9.3% and 11.0%, respectively) steadily increased, whereas dyslipidemia
      (high total cholesterolemia, high triglyceridemia, or low high-density
      lipoproteinemia) and hypertension remained unchanged. We also revealed an
      increase in hemoglobin A1c levels (5.8%, 5.9%, 6.2% and 6.4%, respectively), in
      contrast to modest improvements in lipid levels and blood pressure levels.
      Additionally, patients with multi-vessel disease (MVD, stenosis in more than two
      major coronary vessels) significantly increased from 44.7% in 1993 to 58.8% in
      2003 (p < 0.01). In 1993, DM and dyslipidemia were significant predictors for MVD
      (Odds Ratio: 2.72 and 2.68, respectively). On the other hand, in 2003, the
      significant predictor for MVD shifted to DM alone (Odds Ratio: 2.38). In
      conclusion, the prevalence rate of DM among CAD patients significantly increased
      in this decade, and the consequent increase in the prevalence of MVD should be
      recognized as the most important problem clinically.

PMID- 15557710
TI  - Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL
      particle number in hypertriglyceridemic men - a nuclear magnetic resonance study.
AB  - Hypertriglyceridemia is often associated with small dense low density lipoprotein
      (LDL), elevated remnants, and decreased high density lipoprotein (HDL)
      cholesterol (C), which comprise the dyslipidemic triad. The objective of this
      study was to investigate the effect of fenofibrate on the lipoprotein subfraction
      profile and inflammation markers in hypertriglyceridemic men. Twenty
      hypertriglyceridemic men were administered fenofibrate, 200 mg daily, for 8
      weeks. Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR)
      spectroscopy. Inflammation markers including C-reactive protein (CRP),
      interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were also
      determined. Fenofibrate lowered triglyceride (TG) by 58% and increased HDL-C by
      18%. NMR analysis revealed that very low density lipoprotein (VLDL), particularly
      large VLDL, intermediate density lipoprotein (IDL), and small LDL, were
      significantly decreased, and LDL distribution shifted towards the larger
      particles. HDL distribution was altered; there was an increase in small HDL and a
      decrease in large HDL, resulting in a significant decrease in HDL particle size,
      from 9.1 to 8.9 nm, as well as a 27% increase in HDL particle number. Among
      inflammation markers, CRP was significantly decreased by 42%. In conclusion,
      fenofibrate effectively improves atherogenic dyslipidemia by reducing remnants
      and small LDL, as well as by increasing HDL particles. These effects, together
      with the favorable effect on inflammation, might provide a clinical benefit in
      hypertriglyceridemic subjects.

PMID- 15557711
TI  - Apolipoprotein B as a marker of familial hyperlipoproteinemia.
AB  - AIMS: Families with 10-12-year-old schoolchildren were informed about and asked
      to participate in a study to identify children with hyperlipoproteinemia. We
      hypothesised that children and families with familial blood lipid abnormalities,
      specifically those with familial hypercholesterolemia (FH) and familial combined
      hyperlipidemia (FCHL), could be identified by the child's apolipoprotein B level
      exceeding the 95th percentile. METHODS: Written information and consent was
      distributed to the families. Families whose child had an apoB concentration
      exceeding the 95th percentile were further examined. Children and parents were
      divided into normal, high and very high low density lipoprotein cholesterol
      (LDLC) groups. In adults a high LDLC level was defined as > 4.1-4.9, a very high
      as > 4.9 mmol/l, in children as > 3.4-4.1 and > 4.1 mmol/l, respectively. The
      triglyceride level was regarded as high when > 3.6 mmol/l. RESULTS: Of 2,855
      families, 2,186 agreed to participate. The 95th percentile apoB level was for
      boys 0.98 and girls 1.07 g/l. Of the 131 children with an apoB level above the
      95th percentile, 109 families accepted further examinations. Of 109 hyperapoB
      children 23 were obese. Normal LDLC was found in 28 hyperapo B children of whom
      six parents had high/very high LDLC and one high triglyceride concentrations. A
      high LDLC level was found in 52 children of whom 23 parents had higy/very high
      LDLC and another five high LDLC and/or high triglyceride concentrations. A very
      high LDLC level was found in 29 children, in two of them due to hypothyroidism,
      17 had a parent with high/very high LDLC and another two parents a high
      triglyceride concentration. Familial hypercholesterolemia, defined as a LDLC
      concentration above twice the normal one in the child and a very high level in a
      parent, was suspected in six families, five having a relative with premature CHD.
      The families with FCHL should be included in the 20 families with hyperapoB and a
      child with high-very high LDLC and a parent with very high LDLC or TG levels.
      CONCLUSION: Of the 109 children examined due to the child's increased apoB
      concentration, about 20% were obese and 75% had an increased LDLC concentration.
      A familial occurrence of hyperlipoproteinemia was evident in about 50% of the
      families with an hyperapoB child. Six families probably suffer from familial
      hypercholesterolemia. The definite number of FCHL families could not be defined
      since extended pedigrees were not available. A high suspicion of FCHL was evident
      in 20 families. ApoB is an important marker of hyperlipoproteinemia of familial
      occurrence identifying families in need of primary CHD prevention.

PMID- 15557712
TI  - A case of marked hyperlipoprotein(a)emia associated with nephrotic syndrome and
      advanced atherosclerosis.
AB  - In 1989, we encountered a 68-year-old male patient with marked
      hyperlipoprotein(a)emia (hyperLp(a)emia), who was being treated for hypertension
      and arteriosclerotic obliterans (ASO) at an outpatient clinic of our hospital. He
      began to develop leg edema in 2002 and was referred to the Department of Internal
      Medicine. It was determined that he had severe hyperlipidemia (total cholesterol,
      362 mg/dl), proteinuria, and hypoalbuminemia, suggesting the presence of
      nephrotic syndrome. On lipoprotein analysis, he was found to have very high
      levels of Lp(a) in the plasma (329 mg/dl). Severe atherosclerosis was also found:
      that is, abdominal aortic aneurysm (AAA) and coronary artery disease (CAD) were
      detected, in addition to ASO. After remission of the nephrotic syndrome, the
      plasma Lp(a) level decreased to 204 mg/dl and the total cholesterol concentration
      decreased to 179 mg/dl, while very high levels of Lp(a) persisted. We estimate
      that the markedly elevated Lp(a) plasma levels in this patient may have played
      some role in the progression of atherosclerosis.

PMID- 15557713
TI  - Vasospasms of the radial artery after the transradial approach for coronary
      angiography and angioplasty.
AB  - We examined vasospasms of the radial artery after a transradial approach was used
      for coronary angiography or angioplasty. In forty-eight patients (39 males and 9
      females), arteriography of the radial artery was initially performed just after
      the transradial approach was used for coronary angiography and/or angioplasty.
      Then, five months later, a second arteriography of the radial artery was obtained
      after a transbrachial approach was used for coronary angiography. First and
      second arteriographies were compared to evaluate vaso-spasms of the radial
      artery. In the present study, more than 75% stenosis in the radial artery, 25-75%
      stenosis, and less than 25% stenosis were tentatively defined as severe spasms,
      moderate spasms, and mild spasms, respectively. In arteriographic studies on the
      radial artery, twenty-four patients (50%) had severe radial artery spasms, eleven
      patients (23%) had moderate spasms, and thirteen patients (27%) had mild spasms.
      The diameters of both the proximal and distal radial arteries in the severe spasm
      group were significantly smaller than those in the mild and moderate spasm groups
      (proximal site: severe group 2.39 +/- 0.70 mm versus mild group 2.98 +/- 0.46 mm,
      P < 0.05, and moderate group 2.96 +/- 0.77 mm, P < 0.05, distal site: severe
      group 2.26 +/- 0.60 mm versus mild group 2.73 +/- 0.47 mm, P < 0.05, and moderate
      group 2.86 +/- 0.71 mm, P < 0.05). We concluded that vasospasms of the radial
      artery occurred in most patients after the transradial approach. Furthermore,
      severe radial spasms were strongly correlated with the size of the diameter of
      the artery.

PMID- 15557714
TI  - Excess accumulation of risk factors in ischemic heart disease.
AB  - Though multiple risk factors are commonly observed in patients with ischemic
      heart disease and associated with an increased risk of developing IHD, it has not
      yet been proven that risk factors actually occur in combination more frequently
      than by chance alone. We tested the hypothesis that if some risk factors occur in
      combination, the actual incidences will be higher than the predicted ones which
      were calculated on the assumption that each risk factor occurs independently and
      in combination as a result of coincidence. One hundred consecutive patients were
      included in this study. All had significant stenosis or occlusion of a coronary
      artery. The ages ranged from 50 to 69 years and only males were studied. From the
      incidences of the well-established risk factors in IHD: hypertension, impaired
      glucose tolerance or diabetes mellitus, hypertriglyceridemia, obesity and
      hypercholesterolemia, we determined the actual incidences of combinations of risk
      factors and compared these with the predicted incidences, which were the
      probability calculated from each risk factor. Some of the combinations of 2 to 4
      risk factors were found significantly more often than the predicted ones. Though
      not significant, the reverse was the case in the actual incidence of patients
      having no risk factors. Some combinations of well-known risk factors were found
      more often than the predicted risk factors from the probability and showed a
      tendency to cluster in coronary artery disease patients. Some linking factor must
      be involved in this type of occurrence of risk factors.

PMID- 15557715
TI  - Contractile reserve, thallium-201 reverse redistribution and mismatch between
      perfusion and metabolism in reperfused infarct-related myocardium with delayed
      and incomplete functional recovery.
AB  - We investigated simultaneously the correlations between dobutamine-induced
      contractile reserve (CC), thallium-201 reverse redistribution (RR) and a mismatch
      between perfusion and metabolism (MM) to the magnitude of functional recovery. In
      32 patients with coronary angioplasty early after infarction, echocardiography
      was performed at low-dose dobutamine stress within 1 week and at resting state at
      1 month. Thallium-201/iodine-123 beta-methyl-iodophenyl pentadecanoic acid
      (BMIPP) dual-isotope single photon emission tomography was performed at 1 month.
      Wall motion and the uptake of each tracer were scored as 0 to 2 in the infarct
      related segments, and CC, RR, and MM were evaluated in the infarct-related
      segments. In 71 akinetic or dyskinetic segments before reperfusion, the initial
      thallium-201 uptake and initial BMIPP uptake scores and the 4 hour redistribution
      thallium-201 uptake scores were less severe in the group with complete functional
      recovery (group A), followed by the group with incomplete recovery (group B) and
      then the group with no recovery (group C) (each P < 0.0001). CC was the greatest
      in group A, followed by group B, and then group C (76.2% in 16/21, 60% in 15/25,
      36% in 9/25, P = 0.0212). RR and MM were greater in group B (52% in 13 and 64% in
      16) than in groups A and C (19% in 4 and 8% in 2, 33.3% in 7 and 24% in 6, P =
      0.0013 and P = 0.0113). The intensity of functional damage reflects perfusion and
      metabolism, but the delayed and incomplete functional recovery after reperfusion
      may be closely related to RR, MM, and CC.

PMID- 15557716
TI  - Ventricular unipolar potential in radiofrequency catheter ablation of idiopathic
      non-reentrant ventricular outflow tachycardia.
AB  - We conducted this study to verify the efficacy of ventricular unipolar potential
      (V-uni) for ablation of idiopathic non-reentrant ventricular tachycardia (idio
      VT). The morphology of V-uni at the successful and unsuccessful sites was
      analyzed in 27 patients with idio-VT [20 with right ventricular outflow
      tachycardia (RVOVT) and 7 with left ventricular outflow tachycardia (LVOVT)]. The
      usefulness of V-uni was compared with a pacemapping method and the V-QRS
      interval. The incidence of QS-pattern V-uni at the successful and best
      unsuccessful sites were 100 versus 25% (P = 0.000005) in RVOVT and 86 versus 29%
      (P = 0.10) in LVOVT. The pacemapping scores at the successful and best
      unsuccessful sites were 11.5/12 versus 11.2/12; NS in RVOVT, and 11.2/12 versus
      11.1/12; NS in LVOVT. The mean V-QRS interval at the successful and the best
      unsuccessful sites were 22.5 +/- 3.8 versus 21.6 +/- 3.4 msec; NS in RVOVT, 15.1
      +/- 3.2 versus 12.5 +/- 3.3 msec; NS in LVOVT. The sensitivity (sen) and
      specificity (spe) of QS-pattern V-uni to determine the optimum target sites were
      1.0 and 0.89 in RVOVT and 0.86 and 0.83 in LVOVT, respectively. In the ablation
      of idio-VT, QS-pattern V-uni is simply and visually identifiable, is very useful,
      and should be given a high priority when determining the optimum target site.

PMID- 15557717
TI  - Improvement of atrial signal-averaged electrocardiographic abnormalities after
      radiofrequency catheter ablation in persistent atrial flutter.
AB  - It has been reported that abnormalities of atrial conduction are present in
      patients with atrial flutter (AFL). We analyzed the P wave signal-averaged ECG
      (PSE) in patients after cardioversion of chronic AFL by radiofrequency catheter
      ablation (RFCA) to determine whether abnormalities of atrial conduction exist in
      patients with AFL and whether they recover. We studied 11 patients undergoing
      ablation of persistent AFL (AFL group), 11 patients with paroxysmal AFL (PAFL
      group), and 14 patients without any evidence of arrhythmias (control group). The
      PSEs were recorded 1 day, 7 days, and 1 month after RFCA. The filtered P wave
      duration (FPD) was calculated from the PSE recording. The FPD correlated with
      interatrial conduction time (r = 0.644) and left atrial dimension (r = 0.675) in
      combined assessment of the AFL and PAFL groups. The FPD was longer in the AFL
      group 1 day (165 +/- 14 ms, P < 0.001) and 1 month (150 +/- 18 ms, P < 0.05)
      after RFCA than in the control group (134 +/- 10 ms). Our findings suggest that
      atrial conduction abnormalities detected by PSE are present in patients with
      persistent AFL and improve 1 month after cardioversion.

PMID- 15557718
TI  - Relationship between brain natriuretic peptide, myocardial wall stress, and
      ventricular arrhythmia severity.
AB  - We previously demonstrated that the severity of arrhythmias is reflected by
      circulating brain natriuretic peptide (BNP) concentrations in patients without
      signs of congestive heart failure. In the present study, we evaluated the
      relationships between the severity of the arrhythmia, BNP concentration, and
      echocardiographic findings. The subjects consisted of 52 patients with
      ventricular premature contractions (VPC) but no manifestations of heart failure
      and no digoxin or beta-blocker therapy. Patients underwent Holter monitoring,
      plasma sampling for BNP measurement, and transthoracic echocardiography (TTE). We
      scored the motion of 16 left ventricular segments, deriving a wall-motion score
      index (WMSI) by totaling the scores and dividing by the number of segments
      scored. Twenty-three patients with Lown grade I to II arrhythmias constituted
      group A while group B consisted of 29 Lown III to IV patients. Group B had BNP
      concentrations triple those in group A (57.2 versus 18.1 pg/mL, P < 0.01). Left
      ventricular ejection fraction (LVEF) was similar in groups A and B (65.2% versus
      62.1%, NS). Although left ventricular end-diastolic dimension (LVEDD) was normal
      in both groups, group B exhibited a larger LVEDD than group A (50 versus 46 mm, P
      < 0.005). The correlation (r) between BNP and interventricular septum thickness
      (IVST) was 0.27 (P = 0.013) in group A and 0.37 (P < 0.0001) in group B. Between
      BNP and posterior wall thickness (PWT), the correlation was 0.23 (P = 0.014) in
      group A versus 0.33 (P < 0.0001) in group B. The WMSI in group B was higher than
      in group A (1.34 versus 1.11, P < 0.05). We believe that besides the changes in
      echocardiographic parameters, the BNP elevation in group B could be a response to
      abnormal wall stress from the severe ventricular arrhythmias.

PMID- 15557719
TI  - Regional left atrial coagulation and fibrinolytic activities in patients with
      mitral stenosis.
AB  - Systemic thromboembolism is a major complication of mitral stenosis (MS),
      especially in those patients having atrial fibrillation (AF). Recent evidence has
      suggested that regional left atrial coagulation activity may be increased in MS
      and may contribute to the pathophysiology of left atrial thrombus. However, the
      relation of left atrial coagulation activity to factors that predispose to left
      atrial thrombus formation is unknown. Also, the relations between left atrial and
      systemic coagulation activity, fibrinolysis, and platelet activation remain
      unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin
      III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin
      and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet
      activation, and endothelial dysfunction were measured in 46 patients with MS and
      normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left
      atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the
      corresponding peripheral venous levels (P < 0.05) in patients with MS, being more
      significant in the AF subgroup. There were no significant differences between
      left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and
      factor VIII within the patient group (P > 0.05). The results suggest that there
      are significant variations in the indices of coagulation, fibrinolytic system and
      platelet activation, and endothelial dysfunction between left atrial and
      peripheral venous blood samples of patients with MS that may be due to limited
      spillover from the left atrium to the systemic circulation.

PMID- 15557720
TI  - Effects of exercise training after open heart surgery on quality of life and
      exercise tolerance in patients with mitral regurgitation or aortic regurgitation.
AB  - We conducted a questionnaire survey regarding quality of life (QOL) to evaluate
      the effects of exercise training on the QOL in patients with valvular heart
      disease after surgery. This study included 64 consecutive patients who underwent
      heart surgery. They were divided into two groups: exercise training could (EX(+)
      group, n = 31) and could not be performed (EX(-) group, n = 33) until 6 months
      after surgery. To evaluate the QOL and exercise tolerance, we employed "a
      questionnaire regarding disease and quality of life" developed for Japanese
      people and cardiopulmonary exercise testing. In our questionnaire survey, the
      improvement rating (Delta subjective/social index), which was calculated from the
      difference between the pre-and postoperative values, was greater in the EX(+)
      group than that in the EX(-) group (4.9 +/- 3.1 versus 1.1 +/- 4.0, P < 0.05). In
      the changes in exercise tolerance, Delta anaerobic threshold was greater in the
      EX(+) group (0.79 +/- 0.17 versus -0.02 +/- 0.28, P < 0.01). Moreover, there was
      a positive correlation between Delta subjective/social index and Delta peak VO(2)
      (r = 0.62, P < 0.05). We concluded that exercise training for patients after
      cardiac surgery improves the QOL and exercise tolerance. It is suggested that
      changes in subjective and social parameters contribute to an exercise training
      related improvement in the QOL.

PMID- 15557721
TI  - Effect of acute blood pressure reduction on oxygen uptake kinetics at the onset
      of exercise in hypertensive patients.
AB  - The aim of the present study was to investigate the adverse effects of
      hypertension on the cardiovascular system in daily activities and the effect of
      acute blood pressure reduction on oxygen (O(2)) uptake kinetics. Twenty
      hypertensive patients were included in the study group. Patients performed
      treadmill exercise tests (2.5 km/hour and 5 inclines) twice, before and after
      blood pressure reduction with sublingual captopril. In the control group, ten
      hypertensive patients underwent two tests one hour apart without blood pressure
      reduction brought about by drug therapy. The changes in O(2) kinetic values (O(2)
      deficit and mean response time [MRT]) between the two tests were investigated. In
      the study group, the O(2) deficit and MRT values measured during the first
      exercise testing were found to be 547 +/- 183 mL and 40 +/- 9 seconds, while
      those in the second exercise testing were 401 +/- 127 mL and 34 +/- 7 seconds,
      respectively. In the control group, the O(2) deficit and MRT values measured
      during the first exercise test were 491 +/- 217 mL and 42 +/- 16 seconds and 515
      +/- 159 mL and 41 +/- 13 seconds in the second exercise test. The differences in
      O(2) deficit and MRT in the study group were considered to be statistically
      significant (P = 0.008 and P = 0.004, respectively). Based on our findings, there
      was a significant improvement in O(2) kinetic values with an acute reduction in
      blood pressure in hypertensive patients, most likely as a result of an improved
      response in cardiac output.

PMID- 15557722
TI  - The influence of aldosterone on the development of left ventricular geometry and
      hypertrophy in patients with essential hypertension.
AB  - The identification of risk factors for the initiation of left ventricle
      hypertrophy (LVH), which is an independent risk factor for cardiovascular
      mortality and morbidity in hypertensive patients, is very important. The
      objective of the present study was to identify the relationship of aldosterone
      with LVH and different geometrical patterns of left ventricle that develop in
      patients with essential hypertension. A total of 83 patients with essential
      hypertension (44 females, mean age, 51 +/- 8 years, 39 males, mean age, 57 +/- 10
      years) were included in this study. Thirty-two had LVH. When evaluated according
      to the geometrical patterns of LVH, 18 patients had concentric LVH, 14 had
      eccentric LVH, and 17 had concentric remodeling. Thirty-four patients had normal
      left ventricle geometry. Two weeks after the cessation of antihypertensive
      medications, sodium, potassium, and proteinuria in 24-hour urine samples and
      plasma aldosterone levels and plasma renin activity were measured. Plasma
      aldosterone levels of the patients with LVH were found to be significantly higher
      (9.92 +/- 6.34 ng/dL versus 5.83 +/- 3.5 ng/dL, P < 0.01). The difference between
      plasma renin activities was not statistically significant. Linear regression
      analysis revealed that plasma aldosterone level and age were independent
      parameters increasing left ventricle mass index. The plasma aldosterone levels of
      patients with concentric hypertrophy of the left ventricle were significantly
      higher than those of patients with normal geometry and concentric remodeling.
      There was no significant difference between plasma renin activities. Twenty-four
      hour urine protein concentrations of the patients with LVH were found to be
      significantly higher and sodium to be significantly lower. Plasma aldosterone
      levels seem to be correlated with LVH especially with concentric hypertrophy of
      the left ventricle in patients with essential hypertension.

PMID- 15557723
TI  - Predictors of stable outcome in treating chronic heart failure patients with
      carvedilol.
AB  - Carverdilol has a variable outcome in treating patients with chronic heart
      failure. This prospective single-center study evaluated the predictors of
      clinical variables in determining favorable outcomes in treating chronic heart
      failure patients with carvedilol. The relation between clinical variables and
      maintenance doses of carvedilol was also determined. Seventy chronic heart
      failure patients (mean age, 62.2 years, 50 males and 20 females) with a left
      ventricular ejection fraction < 35% and functional class II-III were enrolled in
      the study. The patients were clinically followed-up for at least 24 months.
      Patients were considered to have a favorable outcome if they had no decreases in
      functional class or quality-of-life score, an increase in left ventricular
      ejection fraction>5%, were not admitted to hospital due to worsening heart
      failure, and free of cardiac mortality. Patients with favorable outcomes had a
      younger age (P = 0.021), higher baseline systolic blood pressure (P = 0.080),
      better baseline functional class (P = 0.001), and a higher tolerated dose of
      carvedilol (P = 0.026) than those in the unfavorable group. In this primarily
      Chinese cohort of chronic heart failure patients, those with favorable outcomes
      were likely to be young, have a high baseline systolic blood pressure, and good
      baseline functional class.

PMID- 15557724
TI  - Tilt training for recurrent neurocardiogenic syncope: effectiveness, patient
      compliance, and scheduling the frequency of training sessions.
AB  - Unsatisfactory results obtained with medical therapy and dual-chamber pacing for
      prevention of recurrent neurocardiogenic syncope necessitated the development of
      new treatment modalities. Tilt-training, a novel treatment for recurrent
      neurocardiogenic syncope based on exercise sessions with prolonged upright
      posture (either on a tilt-table or standing on foot against a wall), was shown to
      be effective in preventing the recurrence of neurocardiogenic syncope. The
      purpose of this study was to demonstrate the long-term beneficial effects of a
      transient tilt training program lasting 2 months. Thirty-two patients with
      recurrent neurocardiogenic syncope (mean number of syncope episodes in the last 6
      months was 3.4 +/- 2.3) constituted the study group. All of the patients were
      tilt test positive. The patients were taught a tilt training program with 2
      phases (in-hospital training with repeated tilt procedures until 3 consecutive
      negative results were obtained and home exercises with standing against a wall)
      and home exercises lasted a maximum of 2 months. After this training program, the
      patients received no treatment and were followed for the recurrence of syncope.
      At the end of the follow-up period (376 +/- 45 days), 81% of the patients were
      free of recurrent syncope. This study revealed that similar successful results
      can also be obtained with a transient tilt training program as a first line
      treatment strategy. Less interference with the daily activities of the patients
      is the major advantage of this strategy. The ease of performance and high
      effectiveness rate will most likely result in more frequent utilization of this
      treatment modality.

PMID- 15557725
TI  - Evaluation of DNA damage in lymphocytes of cardiologists exposed to radiation
      during cardiac catheterization by the COMET ASSAY.
AB  - This study was designed to evaluate the possible in vivo induction of DNA damage
      by exposure to radiation in cardiologists. The alkaline comet assay (single cell
      gel electrophoresis, SCGE), which appears to be a promising tool with which to
      estimate DNA damage at the single cell level, has been used. The assay was
      carried out on 30 cardiologists currently employed in a busy cardiac service and
      30 healthy unexposed controls. Venous blood samples were obtained from the
      exposed and control subjects and SCGE was examined in 100 cells graded as
      undamaged, intermediate, and tailed nuclei. The number of undamaged nuclei was
      almost the same in control and exposed subjects. The extent of DNA migration
      (SCGE assay) did not distinguish between the samples in either the nonsmoker
      exposed or nonsmoker control subjects, which leads one to wonder whether a
      difference in DNA damage really exists. Previous studies reported increased DNA
      damage in blood lymphocytes of smokers. In our study, the percentage of damaged
      cells increased either with the frequency of smoking or exposure to radiation. A
      statistically significant difference was observed both in smokers and exposed
      subjects. In conclusion, the elevated grade of DNA damage in cardiologists
      exposed to radiation indicates a possible genotoxic hazard, therefore, careful
      measures and full cooperation between cardiologists and radiologists should be
      undertaken to reduce the exposure to radiation.

PMID- 15557726
TI  - Use of recombinant activated factor VII in cardiac surgery for an effective
      treatment of severe intractable bleeding.
AB  - Experience gained with administration of supranormal-therapeutic doses (90
      microg/kg) of recombinant activated factor VII in 7 cardiac surgery patients is
      presented. The patients were given recombinant activated factor VII
      postoperatively for intractable bleeding, 5 of them after surgical revision.
      Administration of recombinant activated factor VII was associated with
      significant reduction in blood loss (P < 0.05) and shortening of INR and aPTT in
      laboratory tests. None of the patients needed reoperation. Administration of
      recombinant activated factor VII proved highly effective in management of massive
      hemorrhage in cardiac surgery.

PMID- 15557727
TI  - Three cases of acute myocardial infarction due to coronary embolism: treatment
      using a thrombus aspiration device.
AB  - In this report, we describe three patients with acute myocardial infarction due
      to coronary embolism who were successfully treated using a thrombus aspiration
      device. Thrombus aspiration is shown to be a feasible and effective strategy for
      the treatment of acute coronary embolism.

PMID- 15557728
TI  - Mismatch between results of myocardial fractional flow reserve (FFR) measurements
      and myocardial perfusion SPECT for identification of the severity of ischemia:
      pitfall of FFR in patients with prior myocardial infarction.
AB  - We experienced two rare cases of mismatch between the results of FFR and
      myocardial perfusion SPECT for identification of myocardial ischemia after
      myocardial infarction. If a FFR cutoff value of 0.75 is applied as in angina
      patients to patients with myocardial infarction, the severity of ischemia may be
      underestimated.

PMID- 15557729
TI  - An unusual cause of stroke in a patient with permanent transvenous pacemaker.
AB  - We report the case of a 61-year-old man with a stroke secondary to cerebral
      embolism resulting from inadvertent malposition of a permanent transvenous
      pacemaker lead in the left ventricle. An electrocardiogram and chest X-ray were
      suggestive of a left-sided positioned lead which was confirmed by transthoracic
      echocardiography. Because this malposition was complicated with a cerebrovascular
      event, transcatheter lead extraction was planned, however, the patient chose
      lifelong anticoagulation therapy.

PMID- 15557730
TI  - Severely calcified valvular aortic stenosis firstly diagnosed in monozygotic male
      twins with suspected Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome is a rare and usually sporadic genetic anomaly with an
      estimated frequency of 1:25,000, that also has cardiac defects due to the effect
      on the elastin locus of a deletion on the 7th chromosome. Identical twin boys
      presented with exercise-induced syncope. Echocardiographic examination revealed
      severe calcification at the aortic valves, mitral anterior leaflets, and mitral
      annuli in both cases. A basal interventricular septum was also involved in one
      case. Doppler evaluation demonstrated severe aortic stenosis with a peak gradient
      of 112 and 118 mmHg in both cases. Moderate mitral stenosis was also detected in
      one twin. We performed aortic mechanical valve replacement and dilated the aortic
      annulus with Nick's procedure and evaluated the diagnosis and therapy methods in
      light of the literature. As a result, we determined that these boys are the first
      monozygotic twins who were diagnosed during childhood.

PMID- 15557731
TI  - A second mitral valve replacement in a patient with hereditary hemorrhagic
      telangiectasia (Osler's disease).
AB  - A 62-year-old female with Osler's disease was admitted to our hospital because of
      fever and cardiac failure. The patient had undergone a mitral valve replacement
      (MVR) using a Carpentier-Edwards prosthetic valve 14 years earlier. A bacterial
      examination of arterial blood identified Streptococcus mitis. No arteriovenous
      malformations were detected in visceral organs. The patient underwent MVR using
      the same prosthetic xenograft after conservative treatment and management of
      repetitive epistaxis and decayed teeth. Intra- and postoperative bleeding were
      typical of a mitral valve reoperation. This is the first reported experience, to
      the best of our knowledge, of a second MVR in a patient with Osler's disease.

PMID- 15557732
TI  - Reversible left ventricular dysfunction "takotsubo" cardiomyopathy associated
      with hyperthyroidism.
AB  - Myocardial stunning with hyperthyroidism is rare. A 79-year old woman with
      hyperthyroidism was admitted to our hospital complaining of palpitations due to
      paroxysmal atrial fibrillation. An echocardiogram showed akinesis of the apical
      wall which was not observed 2 weeks before admission. Cardiac catheterization
      performed in the acute phase showed normal coronary arteries and no evidence of
      provocative spasms. The wall motion abnormality disappeared entirely after 1 week
      in hospital. We report a case of transient left ventricular dysfunction, so
      called "takotsubo" cardiomyopathy, associated with hyperthyroidism.

PMID- 15557733
TI  - Molecular mechanisms and drug development in aquaporin water channel diseases:
      water channel aquaporin-2 of kidney collecting duct cells.
AB  - Aquaporin-2 (AQP2) is one of the membrane water channel proteins expressed in
      principal cells of the kidney collecting ducts. In the basal state, AQP2 resides
      in the storage vesicles localized in the subapical cytoplasm. Upon stimulation
      with vasopressin, AQP2 is translocated to the apical plasma membrane by the
      exocytic fusion of the storage vesicles with the apical membrane. This
      translocation enables the transepithelial reabsorption of water from the lumen to
      the interstitium via AQP2 at the apical membrane and AQP3/AQP4 at the basolateral
      membrane. AQP2-storage vesicles are distinct from the endoplasmic reticulum,
      Golgi apparatus, trans-Golgi network, and lysosomes. The early endosomal marker
      EEA1 is colocalized with some of AQP2 vesicles. Further analyses in Madin-Darby
      canine kidney (MDCK) cells transfected with AQP2 revealed that subapical Rab11
      positive/EEA1-negative smaller vesicles constitute part of the AQP2 storage
      vesicles for the translocation to the apical membrane. Termination of stimulation
      results in the retrieval of AQP2 to the larger EEA1-positive early endosomal
      compartment. AQP2 is then transferred to the subapical storage compartment in a
      PI3-kinase-dependent manner. GLUT4 is an isoform of glucose transporters whose
      localization is also regulated by vesicular trafficking induced by insulin
      stimulation. Comparison of the intracellular localization of AQP2 with GLUT4
      suggests distinct regulation of AQP2 trafficking.

PMID- 15557734
TI  - Molecular mechanisms and drug development in aquaporin water channel diseases:
      structure and function of aquaporins.
AB  - The discovery of the water channel aquaporin has greatly expanded our
      understanding of the regulation of the water permeability of biological
      membranes. The atomic structure of aquaporin-1 (AQP1) demonstrated how aquaporin
      is freely permeated by water but not protons and provided marked insight into
      several human disorders. Eleven mammalian aquaporins have been identified, each
      with a distinct distribution, and these are selectively permeated by water or
      water plus glycerol. Aquaporins are suspected in numerous pathological conditions
      involving fluid transport such as brain edema. Knowledge of aquaporin structure
      may provide insight into the development of new therapeutics through appropriate
      drug design.

PMID- 15557735
TI  - Molecular mechanisms and drug development in aquaporin water channel diseases:
      aquaporins in the brain.
AB  - Water homeostasis of the brain is essential for its neuronal activity. Changes in
      water content in the intra- and extra-cellular space affect ionic concentrations
      and therefore modify neuronal activity. Aquaporin (AQP) water channels may have a
      central role in keeping water homeostasis in the brain. Among AQP subtypes cloned
      in mammalian, only AQP1, AQP4, and AQP9 were identified in the brain. Changes in
      AQP expression may be correlated with edema formation of the brain. In this
      review, we describe the physiological function of AQPs and the regulatory
      mechanism of their expression in the brain.

PMID- 15557736
TI  - Effects of methanol extract of Uncariae Ramulus et Uncus on ibotenic acid-induced
      amnesia in the rat.
AB  - In the present study, we investigated the effects of Uncariae Ramulus et Uncus
      (UR) on learning and memory in the Morris water maze task and the central
      cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the
      water maze test, the animals were trained to find a platform in a fixed position
      during 6 days and then received a 60-s probe trial in which the platform was
      removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired
      performance of the maze test and severe cell losses in the septohippocampal
      cholinergic system (SHC), as indicated by decreased choline acetyltransferase
      immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily
      administrations of UR (100 mg/kg, i.p.) for 21 consecutive days produced
      significant reversals of ibotenic acid-induced deficit in learning and memory.
      These treatments also reduced the loss of cholinergic immunoreactivity in the
      hippocampus induced by ibotenic acid. These results demonstrated that impairments
      of spatial learning and memory may be attributable to degeneration of SHC neurons
      and that UR ameliorated learning and memory deficits partly through
      neuroprotective effects on the central acetylcholine system. Our studies suggest
      that UR may be useful in the treatment of Alzheimer's disease.

PMID- 15557737
TI  - Microarray analysis of temperature-induced transcriptome of Yersinia pestis.
AB  - Yersinia pestis, the etiologic agent of plague, must acclimatize itself to
      temperature shifts between the temperature (26 C) for flea blockage and the body
      temperature (37 C) of warm-blooded hosts during its life cycle. Here a whole
      genome DNA microarray was used to investigate transcriptional regulation upon the
      upshift of growth temperature from 26 to 37 C in a chemically defined medium.
      Four hundred and one genes were regulated differentially under the two
      temperatures. About 39% of these genes were up-regulated at 37 C, whereas 61%
      were down-regulated. Temperature-induced changes occurred at the level of
      transcription of genes encoding proven or predicted virulence factors,
      regulators, metabolism-associated proteins, prophages, and hypothetical proteins.
      Strikingly, many gene clusters displayed a co-transcription pattern in response
      to temperature upshift. Our data provided a genome-wide profile of gene
      transcription induced by temperature shift and should shed light on the
      pathogenicity and host-microbe interaction of this deadly pathogen.

PMID- 15557738
TI  - Role of p38 mitogen-activated protein kinase (MAPK) for vacuole formation in
      lipopolysaccharide (LPS)-stimulated macrophages.
AB  - The role of p38 mitogen-activated protein kinase (MAPK) on vacuole formation in
      lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was examined. LPS definitely
      induced the formation of vacuoles in RAW 264.7 cells and SB202190 as a p38
      specific inhibitor also induced slight vacuole formation. The simultaneous
      treatment with LPS and SB202190 induced many more vacuoles in RAW 264.7 cells
      than the treatment with LPS or SB202190 alone, and the vacuoles were
      extraordinarily large in size. On the other hand, an inactive inhibitor of p38
      MAPK did not augment LPS-induced vacuole formation. Further, the inhibitors of
      other MAPKs and nuclear factor (NF)-kappaB pathways did not affect it. The
      extraordinarily large vacuoles in RAW 264.7 cells treated with LPS and SB202190
      were possibly formed via fusion of small vacuoles. However, SB202190 did not
      augment vacuole formation in CpG DNA or interferon (IFN)-gamma-stimulated RAW
      264.7 cells. The role of p38 MAPK in the vacuole formation in LPS-stimulated
      macrophages is discussed.

PMID- 15557739
TI  - Nocardia aobensis Sp. Nov., isolated from patients in Japan.
AB  - Five clinical isolates, strains IFM 0137, 0372(T), 0496, 0556, and 0952, were
      provisionally assigned to the genus Nocardia based on morphological criteria.
      Nearly complete 16S rDNA sequences were determined for these strains. These data
      showed that they are most similar to that of Nocardia africana, Nocardia
      cerradoensis and Nocardia veterana. However, DNA-DNA relatedness data showed that
      the five strains were of a single species and were distinguishable from N.
      africana, N. cerradoensis and N. veterana. Therefore, these strains represent a
      new species within the genus Nocardia. The designation of these five strains is
      Nocardia aobensis sp. nov. The type strain is IFM 0372(T) (=NBRC 100429(T)=JCM
      12352(T)=DSM 44805(T)).

PMID- 15557740
TI  - Effects of endocytosis inhibitory drugs on rubella virus entry into VeroE6 cells.
AB  - It has been suggested that infectious entry of rubella virus (RV) is conducted by
      receptor mediated endocytosis. To explore the cellular entry mechanism of RV,
      inhibitory effects of drugs affecting various endocytic pathways on RV entry into
      VeroE6 cells were analyzed. Results showed that RV infectious entry into VeroE6
      cells is mediated by clathrin-dependent endocytosis and not by caveolae-mediated
      endocytosis. Moreover, chemical inhibition of macropinocytosis such as treatments
      of amiloride, actin and microtubule-disrupting drug significantly reduced RV
      infection. Considering that macropinocytosis is inducible endocytosis by cellular
      stimulations, clathrin-mediated endocytosis is likely to be a major route of RV
      infectious entry.

PMID- 15557741
TI  - Growth and virulence alterations of equine herpesvirus 1 by insertion of a green
      fluorescent protein gene in the intergenic region between ORFs 62 and 63.
AB  - Nucleotide sequences of the intergenic region between ORF 62 and ORF 63 of equine
      herpesvirus 1 (EHV-1) isolates were analyzed. The sequences of this region
      consisted of variable and conserved domains among EHV-1 isolates. An EHV-1
      mutant, Ab4-GFP, was constructed by inserting a green fluorescent protein (GFP)
      expression cassette flanked by lox P at both ends into the intergenic region
      between ORF 62 and ORF 63. Another mutant, Ab4-loxP, which contains one lox P
      site, was constructed by excision of the GFP cassette from the Ab4-GFP virus
      genome by cre enzyme. The recombinant Ab4-GFP formed smaller plaques than the
      wild type in MDBK cells. Virus production also decreased for Ab4-GFP in multistep
      growth analyses. Virulence of Ab4-GFP in both mice and hamsters was weaker than
      that of the wild type. Ab4-loxP exhibited properties similar to those of the wild
      type. These results suggest that the intergenic region between ORF 62 and ORF 63
      plays various roles in the virus growth.

PMID- 15557742
TI  - Epizootiological and epidemiological study of hantavirus infection in Japan.
AB  - Epizootiological surveys on hantavirus infections in rodents were carried out in
      various areas of Japan, including the four major islands of Hokkaido, Honshu,
      Shikoku, and Kyushu from 2000 to 2003. A total of 1,221 rodents and insectivores
      were captured. Seropositive animals were found in Apodemus (A.) speciosus (5/482,
      1.0%), Rattus (R.) norvegicus (4/364, 1.1%), R. rattus (3/45, 6.7%), and
      Clethrionomys (C.) rufocanus (7/197, 3.6%). The partial S segment was amplified
      from one seropositive R. rattus captured at Hakodate. The nucleotide sequence
      showed 96% identity with the Seoul virus (SEOV) prototype strain SR-11. In
      addition, we conducted an epidemiological survey on human hantavirus infection in
      a high-risk population, the personnel of the Japan Ground Self-defense Force on
      Hokkaido. One out of 207 human blood samples was positive for anti-hantavirus
      antibody by IFA, ELISA, and WB analysis. The result of the serotype specific
      ELISA indicates that this individual acquired SEOV infection. This study
      indicates that A. speciosus, R. norvegicus, R. rattus, and C. rufocanus carry
      hantaviruses as the reservoir animals in Japan. Infected R. rattus and R.
      norvegicus in port areas could be the sources of human SEOV infection and a
      threat to travelers and individuals working in seaports.

PMID- 15557743
TI  - Studies on the conditions required for structural and functional maturation of
      rabies virus glycoprotein (G) in G cDNA-transfected cells.
AB  - When the rabies virus G cDNA was expressed with the help of T7 RNA polymerase
      provided by a recombinant vaccinia virus (RVV-T7), functional G proteins were
      produced in terms of their ability to induce low pH-dependent syncytium formation
      and the formation of conformational epitopes, including the acid-sensitive
      epitope recognized by mAb #1-30-44. Such an ability and the 1-30-44 epitope
      formation, however, were not associated with the G gene products when G cDNA was
      expressed without the help of RVV-T7 using a tetracycline-regulated expression
      vector (pTet-G), although they were normally transported to the surface of
      established G protein-producing BHK-21 (G-BHK) cells. But, when the G-BHK cells
      were treated with 2.5 m M sodium butyrate (NaB) after the removal of
      tetracycline, we could observe not only a much increased frequency of G protein
      producing cells, but also the greatly enhanced maturation of the protein. Another
      short acylate, sodium propionate (NaP), similarly induced increased G protein
      synthesis at a concentration of 2.5 m M as NaB; however, such proteins were
      mostly not endowed with the fusion activity nor the 1-30-44 epitope, while NaP at
      a higher concentration as 5.0 m M did induce similarly the increased production
      and enhanced maturation of G protein, including the 1-30-44 epitope formation.
      From these results, we conclude that functional maturation of G protein to
      acquire fusogenic activity is correlated with 1-30-44 epitope formation, and 2.5
      m M NaB not only stimulates G protein production, but also provides such cellular
      conditions as are required for the structural and functional maturation of the
      protein.

PMID- 15557744
TI  - Further studies on the hyperphosphorylated form (p40) of the rabies virus nominal
      phosphoprotein (P).
AB  - We investigated possible mechanisms involved in production of a
      hyperphosphorylated form (p40) of rabies virus P protein, to which two
      dimensional (2-D) gel electrophoresis was applied. The P gene products produced
      in Escherichia coli cells could be detected as a single spot of unphosphorylated
      37-kDa form (termed as p37-0) in a 2-D gel. The 37-kDa proteins in the virus
      infected cells are composed of some phosphorylated forms, including a major p37-1
      and more phosphorylated minor forms (e.g., p37-2, p37-3, etc.), but little p37-0
      is detected (Eriguchi et al., 2002). When the E. coli -produced P protein
      analogues were incubated with BHK-21 cell lysates, heparin-sensitive
      phosphorylation occurred as described previously (Takamatsu et al., 1998), giving
      an additional 40-kDa spot. However, such a p40-like derivative displayed a little
      more basic pI value than that of the authentic p40 produced in the infected
      cells; hence, the former was termed p40-0 (pI=4.78), while the latter, p40-1
      (pI=4.73). In contrast, p40 produced in the P cDNAtransfected animal cell was
      detected at the p40-1 position. In addition, staurosporine did not affect the p40
      1 production in virus-infected nor the P cDNA-transfected animal cells, while the
      agent reduced production of hyperphosphorylated forms of p37, resulting in
      accumulation of p37-1, but not of p37-0. These results suggest that, although p37
      0 may become a substrate for the heparin-sensitive protein kinase (PK) in vitro,
      only p37-1 is a substrate for p40 production catalyzed by heparin-sensitive PK in
      animal cells, and staurosporine-sensitive PK is involved in the production of
      more phosphorylated forms of p37, but not in p37-1 production from p37-0.

PMID- 15557745
TI  - Stimulation of phagocytosis of influenza virus-infected cells through surface
      desialylation of macrophages by viral neuraminidase.
AB  - Cells infected with influenza A virus undergo apoptosis and become susceptible to
      phosphatidylserine-mediated phagocytosis by macrophages. This study was
      undertaken to elucidate the mechanism underlying our previous finding that the
      activity of viral neuraminidase (NA) is required for efficient phagocytosis.
      Treatment of macrophages, not influenza virus-infected cells, with Arthrobacter
      ureafaciens NA or virus-infected cells expressing viral NA augmented the level of
      phagocytosis of virus-infected cells but not of latex beads or cells undergoing
      Fas-induced apoptosis. Oligosaccharides, including sialyllactose, bound to
      influenza virus-infected cells and inhibited phagocytosis by macrophages. These
      results indicate that surface desialylation of macrophages by influenza virus NA
      modulates the mode of association between macrophages and target virus-infected
      cells and stimulates phosphatidylserine-mediated phagocytosis.

PMID- 15557746
TI  - Study on immunological status of Chinese HIV-infected individuals.
AB  - HIV-1 infection is characterized by a gradual decline of immune function, and the
      immune dysfunction is widely regarded as one of the most important determinants
      of disease progression. The present study was performed to analyze in more detail
      the immunological status of HIV-infected people in China. T cell counts,
      activation of T cells, HIV-1 specific CTL and plasma levels of cytokines were
      determined with flow cytometry, IFN-gamma Elispot or ELISA techniques. The HIV
      viral load was negatively correlated with CD4(+), CD8(+) T cell counts (r=-0.654,
      P<0.001; r=-0.228, P<0.05); the breadth and magnitude of HIV-1 specific CTL
      responses against HIV-1 Gag peptides was related to disease progression; the
      activation of CD8(+) T cells was significantly higher than that in HIV-negative
      controls; the level of plasma IL-12 was much lower and the plasma IFN-gamma, IL
      10 and IL-6 were much higher in HIV-infected persons than in HIV-negative
      controls (P<0.05). Study on immunological status in HIV-infected Chinese is very
      important in predicting the disease progression and providing information for
      HAART therapy in China.

PMID- 15557747
TI  - Novel evidence suggesting Clostridium difficile is present in human gut
      microbiota more frequently than previously suspected.
AB  - Prevalence rate of Clostridium difficile in healthy human adults is believed to
      be very low. Our RT-PCR system using glass powder, which can eliminate PCR
      inhibitors, detected C. difficile toxin B mRNA in 16 of 30 fecal samples (53.3%)
      from healthy human adults. In contrast, we failed to detect toxin B in the same
      fecal samples by PCR using DNA templates extracted with phenol-chloroform. Our
      results suggest that PCR inhibitors in feces carried through phenol-chloroform
      extraction procedure might suppress the sensitivity of PCR and that C. difficile
      is actually present in human gut microbiota more frequently than previously
      suspected.

PMID- 15557748
TI  - Rapid identification of Borrelia burgdorferi sensu lato by PCR-restriction
      fragment length polymorphism analysis of groEL gene.
AB  - Thirty-one reference strains and 23 Korean isolates of the genus Borrelia were
      identified through the PCR-RFLP analysis using the groEL gene. This will be
      useful for the rapid differentiation of B. burgdorferi sensu lato and complements
      one of the 5S-23S intergenic spacers.

PMID- 15557749
TI  - The throat flora and its mitogenic activity in patients with Kawasaki disease.
AB  - The etiology of Kawasaki disease (KD) remains unknown, although some infectious
      organism has been suggested as the cause. Recent studies suggest that some
      bacterial toxins with superantigen activity are involved in its pathogenesis, but
      no specific bacterial toxin has yet been identified. Throat swabs for bacterial
      culture were obtained from 21 patients with KD and 20 with other febrile
      illnesses as controls. Mitogenic activity in culture supernatants obtained from
      individual bacterial strains was measured by lymphocyte proliferation assay.
      Sixty-one bacterial strains were isolated from KD patients, and 62 strains from
      control patients. There was no apparent difference in bacterial species in the
      throat flora between KD patients and febrile controls. Moreover, total and
      individual mitogenic activity of strains from KD patients was no greater than
      that of strains from febrile controls. The bacterial superantigen activity of
      throat flora may not play a major role in the pathogenesis of KD.

PMID- 15557750
TI  - Antibodies to human-related H3 influenza A virus in Baikal seals (Phoca sibirica)
      and ringed seals (Phoca hispida) in Russia.
AB  - Antibodies to influenza A virus were detected using enzyme-linked immunosorbent
      assay (ELISA) in the sera from two of seven Baikal seals (Phoca sibrica) and from
      five of six ringed seals (Phoca hispida) in Russia. In a hemagglutination
      inhibition test using H1-H15 reference influenza A viruses, ELISA-positive sera
      from one Baikal seal and four ringed seals reacted to A/Aichi/2/68 (H3N2) and
      A/Bangkok/1/79 (H3N2) strains. One ringed seal serum sample reacted to
      A/seal/Massachusetts/1/80 (H7N7). The present results suggested that human
      related H3 viruses were prevalent in Baikal seals and ringed seals inhabiting the
      central Russian Arctic.

PMID- 15557751
TI  - Roles of Toxoplasma gondii-derived heat shock protein 70 in host defense against
      T. gondii infection.
AB  - C57BL/6 mice receiving intraperitoneal injection of Toxoplasma gondii -derived
      heat shock protein 70 (T.g. HSP70) on day 3 post T. gondii infection succumbed by
      day 9 post infection, while vector protein-injected control mice survived more
      than 6 months. The deteriorating effect of T.g. HSP70 on host immune responses
      was dose-dependent. By T.g. HSP70 injection, T. gondii loads increased in various
      organs of T. gondii-infected mice. Th2 cytokines such as IL-4 and IL-10 were
      continuously produced from spleen and peritoneal exudate cells of T. gondii 
      infected mice by injection of T.g. HSP70. Furthermore, nitric oxide production
      from peritoneal macrophages in T. gondii-infected mice was reduced by T.g. HSP70.

PMID- 15557752
TI  - Tissue microarray analysis of cyclin D1 gene amplification and gain in colorectal
      carcinomas.
AB  - Colorectal cancer is one of the most common neoplastic diseases and one of the
      leading causes of cancer-related deaths. Elevated beta-catenin levels in
      colorectal cancer result in the binding of beta-catenin to LEF-1 and increased
      transcriptional activation of the CCND1 gene. Overexpression of cyclin D1 is
      observed in one third of colorectal tumors. CCND1 amplification is the main cause
      of protein overexpression in numerous human carcinomas. In colorectal cancer,
      however, no CCND1 amplification has been reported so far. The aim of this study
      was to determine the frequency of CCND1 amplifications and gains in a large
      number of colorectal carcinomas, arranged in a tissue microarray, in order to
      assess their role in colorectal cancer development. The copy number changes,
      detected by fluorescence in situ hybridization, were predominantly gains (7.6%)
      and only rarely amplifications (2.5%). In colorectal cancer, the CCND1 copy
      number increase was neither associated with the tumor phenotype (stage and grade)
      nor with the tumor localization (colon, rectum or sigmoid colon). In conclusion,
      even in a small number of colorectal tumors, CCND1 gene amplification is a
      possible mechanism for the increase in cyclin D1 oncoprotein.

PMID- 15557753
TI  - Alteration of frizzled expression in renal cell carcinoma.
AB  - To evaluate the involvement of frizzled receptors (Fzds) in oncogenesis, we
      investigated mRNA expression levels of several human Fzds in more than 30
      different human tumor samples and their corresponding (matched) normal tissue
      samples, using real-time quantitative PCR. We observed that the mRNA level of
      Fzd5 was markedly increased in 8 of 11 renal carcinoma samples whilst Fzd8 mRNA
      was increased in 7 of 11 renal carcinoma samples. Western blot analysis of crude
      membrane fractions revealed that Fzd5 protein expression in the matched
      tumor/normal kidney samples correlated with the observed mRNA level. Wnt/beta
      catenin signaling pathway activation was confirmed by the increased expression of
      a set of target genes. Using a kidney tumor tissue array, Fzd5 protein expression
      was investigated in a broader panel of kidney tumor samples. Fzd5 membrane
      staining was detected in 30% of clear cell carcinomas, and there was a strong
      correlation with nuclear cyclin D1 staining in the samples. Our data suggested
      that altered expression of certain members of the Fzd family, and their
      downstream targets, could provide alternative mechanisms leading to activation of
      the Wnt signaling pathway in renal carcinogenesis. Fzd family members may have a
      role as a biomarker.

PMID- 15557754
TI  - Antisense and dominant-negative AKT2 cDNA inhibits glioma cell invasion.
AB  - The aim of this study was to explore the potential role of AKT2 in glioma cell
      invasion. Therefore, dominant-negative (DN-AKT2) and antisense AKT2 constructs
      (AS-AKT2) were transfected into rat C6 glioma cells with elevated endogenous AKT2
      expression. In situ hybridization and Western blot analysis were used to identify
      AKT2 expression. Spheroid culturing was used to assess cell migration and
      invasion in Matrigel from spheroids. Cell motility and invasion were also
      evaluated by scratch and Transwell invasion assays, respectively. The secretion
      of matrix metalloproteinases (MMPs), MMP2 and MMP9, was determined by gelatin
      zymography. AKT2 expression was inhibited in C6 cells transfected with AS-AKT2
      but did not significantly change in cells transfected with DN-AKT2. The cell
      migration distance from spheroids or the number of cells migrating into the
      acellular space created by scratching was reduced in cells transfected with DN
      AKT2 or AS-AKT2 compared to the control cells. The invasive distance of cells
      from the spheroids in Matrigel sandwich and the number of invading cells through
      the Matrigel were also decreased in the DN-AKT2- and AS-AKT2-transfected cells.
      Gelatin zymography showed that the production of MMP2 and MMP9 was inhibited in
      transfected cells. In conclusion, AKT2 plays an important role in glioma cell
      motility and invasion. Therapy based on AKT inhibition may complement currently
      available treatment to control glioma cell invasion.

PMID- 15557755
TI  - Production and characterization of a new antibody specific for the mutant EGF
      receptor, EGFRvIII, in Camelus bactrianus.
AB  - EGFRvIII is the type III deletion mutant form of the epidermal growth factor
      receptor (EGFR) with transforming activity. This tumor-specific antigen is ligand
      independent, contains a constitutively active tyrosine kinase domain and has been
      shown to be present in a number of human malignancies. In this study, we report
      the production and characterization of camel antibodies that are directed against
      the external domain of the EGFRvIII. Antibodies developed in camels are smaller
      (i.e. IgG2 and IgG3 subclasses lack light chains) than any other conventional
      mammalian antibodies. This property of camel antibodies makes them ideal tools
      for basic research and other applications such as tumor imaging and cancer
      therapy. In the present study, camel antibodies were generated by immunization of
      camelids (Camelus bactrianus and Camelus dromedarius) with a synthetic 14-amino
      acid peptide corresponding to the mutated sequence of the EGFR, tissue
      homogenates of several patients with human glioblastoma, medulloblastoma and
      aggressive breast carcinoma, as well as EGFR-expressing cell lines. Three
      subclasses of camel IgG [conventional (IgG1, 160 kD) and heavy chain-only
      antibodies (IgG2 and IgG3, 90 kD)] were separated by their different binding
      properties to protein A and protein G affinity columns. The anti-EGFRvIII peptide
      antibodies from immunized camels were purified further using the EGFRvIII
      synthetic peptide affinity column. The purified anti-EGFRvIII peptide camel
      antibodies selectively bound to the EGFRvIII peptide and affinity-purified
      EGFRvIII from malignant tissues and detected a protein band of 140 kD from
      malignant tissues by Western blot. Affinity analysis showed that the antibodies
      from C. bactrianus and C. dromedarius reacted with peptide and antigen purified
      from a small cell lung cancer ascitic fluid with affinities of 2 x 10(8) and 5 x
      10(7)M(-1) to the same extent, respectively. Since the functional antigen-binding
      domain of the anti-EGFRvIII antibodies in camels is much simpler and located only
      on the heavy chains of proteins, we are currently developing recombinant and
      smaller versions of the variable domain of these naturally occurring heavy-chain
      antibodies (V(HH)) for use in tumor imaging and cancer therapy.

PMID- 15557756
TI  - Matrix metalloproteinases 2 and 9 and their tissue inhibitors in low malignant
      potential ovarian tumors.
AB  - OBJECTIVES: This study aimed to analyze the expression of matrix
      metalloproteinases 2 (MMP-2) and 9 (MMP-9) and their tissue inhibitors TIMP-1 and
      TIMP-2 in low malignant potential (LMP) ovarian tumors and to compare these
      values with those recorded for benign and malignant ovarian neoplasms. METHODS: A
      total of 53 ovarian tumors (16 benign, 15 LMP and 22 malignant) were evaluated by
      immunohistochemistry for the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2.
      RESULTS: MMP-2 expression was found in 56% of the benign, 40% of the LMP, and 90%
      of the malignant ovarian tumors (benign vs. malignant, p = 0.021; LMP vs.
      malignant, p = 0.002). The expression of MMP-9, TIMP-1 and TIMP-2 was lower in
      the benign and LMP tumors compared with the malignant ones. CONCLUSION: The data
      suggest that, in relation to the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2,
      LMP ovarian tumors are more similar to benign than to malignant ovarian tumors.

PMID- 15557757
TI  - Human kallikrein 6 degrades extracellular matrix proteins and may enhance the
      metastatic potential of tumour cells.
AB  - Human kallikrein 6 (hK6), a trypsin-like serine protease, is a newly identified
      member of the kallikrein gene family. Its involvement in inflammatory CNS lesions
      and in demyelination has been reported. Recent work has suggested that expression
      of this enzyme is significantly elevated in patients with ovarian cancer. We have
      identified many tumour cell lines that secrete hK6, but its physiological role is
      unknown. Here, we try to unveil the role of this kallikrein in the metastasis and
      invasion of tumour cells. We demonstrate that purified human recombinant hK6 can
      cleave gelatin in zymography and can efficiently degrade high-molecular-weight
      extracellular matrix proteins such as fibronectin, laminin, vitronectin and
      collagen. In Boyden chamber assays, we found that tumour cells treated with a
      neutralizing hK6 antibody migrate less than control cells. We conclude that hK6
      might play a role in the invasion and metastasis of tumour cells and may be a
      candidate therapeutic target.

PMID- 15557758
TI  - The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a
      relationship?
AB  - Mutations in the TP53 gene are found in about 11% of melanomas. Although nearly
      600 papers have been published with varying degrees of consensus, there does not
      appear to be any comparable analysis that facilitates more than a glimpse into
      the role of p53 in melanomagenesis. This article reviews p53 alterations (at the
      gene and protein levels) in melanocytic skin lesions and discusses the following
      points: (i) p53 alterations commence as early as at the stage of benign and
      dysplastic nevi; (ii) these alterations are frequent in melanomas, and gradually
      increase with their progression; (iii) there is no concordance between the
      frequent p53 protein expression and the rarity of both TP53 gene mutations in
      melanomas, and (iv) the entire p53 pathway is a more critical determinant of the
      fate of the melanocytic skin lesions than the status of the p53 protein or the
      gene itself.

PMID- 15557759
TI  - Strategies to endow cytotoxic T lymphocytes or natural killer cells with antibody
      activity against carcinoembryonic antigen.
AB  - Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are main effecter
      cells in cellular immunity against tumor cells. T-cell immunotherapy is based on
      the assumption that tumor(-associated) antigen (TA) peptides are correctly
      presented by HLA class I molecules on target tumor cells, and NK cell
      immunotherapy is based on the hypothesis that cell surface TAs or ligands for NK
      receptors are widely expressed in tumor cells. However, human tumor cells often
      lose HLA class I molecules, and target cell ligands for NK receptors are not
      always expressed in human tumor cells. These altered HLA class I phenotypes and
      non-ubiquitous expression of NK receptor ligands constitute the major tumor
      escape mechanism facing tumor-specific CTL and/or NK cell mediated responses.
      These facts also indicate that it is not easy to eliminate the target tumors only
      by activating tumor-specific CTLs or NK cells with cancer vaccine treatments. On
      the other hand, it is easily confirmed by immunohistochemistry whether or not
      antibody-recognized TAs exist on the cell surface of target tumor cells.
      Therefore, endowing CTLs or NK cells with antigen-binding specificity of anti-TA
      antibody is a promising approach for re-targeting the activities of these
      effector cells to tumor cells in an HLA-independent manner. This review
      summarizes the following four new strategies for re-targeting CTLs or NK cells to
      carcinoembryonic-antigen-expressing tumor cells: (1) bispecific antibody
      technology; (2) antibody-cytokine fusion protein technology; (3) chimeric immune
      receptor technology, and (4) antibody-HLA/peptide complex technology.

PMID- 15557760
TI  - Up close and personal: molecular diagnostics in oncology.
AB  - The almost overwhelming volume of information and new technological developments
      that has demanded so much of our scientific attention over the last decade will
      shortly revolutionize clinical diagnostics. Some of these developments are
      already affecting the working lives of scientists and clinicians alike, but will
      eventually require a greater understanding and acceptance from a much wider
      audience. Therefore it is important in our current scientific endeavor and
      commercial enthusiasm for molecular diagnostics that we maintain some awareness
      of the significant obstacles that must be overcome if we are to see an
      appropriate, timely and widespread adoption of molecular diagnostic testing in
      oncology. This article presents a brief commentary on the current state of the
      art in molecular diagnostics in oncology and how this relates to a more
      personalized approach to treatment.

PMID- 15557761
TI  - Nelson's syndrome: complete remission with cabergoline but not with bromocriptine
      or cyproheptadine treatment.
AB  - A woman affected by Cushing's disease underwent bilateral adrenalectomy followed
      by radiotherapy of the hypothalamic-pituitary area when she was 18 years old.
      Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided
      into two daily doses). At the age of 26 years, the patient exhibited the clinical
      signs of the Nelson's syndrome, i.e. skin and gingival hyperpigmentation
      accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal
      range 15-80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar
      region evidenced a pituitary macroadenoma, measuring 14 x 13 mm. The patient was
      initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months.
      There was a partial improvement of the symptoms, with a reduction of the ACTH
      plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due
      to sleepiness and weight gain, the cyproheptadine treatment was interrupted and
      substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after
      cabergoline was applied an improvement of the clinical symptoms and signs was
      observed such as a regression of the tumor mass and the normalization of the ACTH
      plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine
      (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and
      headache and cutaneous hyperpigmentation were recorded. When cabergoline was
      reintroduced there was a clinical improvement and normalization of ACTH plasma
      levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete
      remission of the pituitary adenoma. The results obtained show for the first time
      that a long-term treatment with cabergoline also brings about a complete
      remission of Nelson's syndrome in the presence of a pituitary macroadenoma.

PMID- 15557762
TI  - DNA microarray analysis of pancreatic malignancies.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To
      improve the prognosis, novel molecular markers and targets for earlier diagnosis
      and adjuvant and/or neoadjuvant treatment are needed. Recent advances in human
      genome research and high-throughput molecular technologies make it possible to
      cope with the molecular complexity of malignant tumors. With DNA array
      technology, mRNA expression levels of thousand of genes can be measured
      simultaneously in a single assay. As several studies using microarrays in PDAC
      have already been published, this review attempts to compare the published data
      and therefore to validate the results. In addition, the applied techniques are
      discussed in the context of pancreatic malignancies.

PMID- 15557763
TI  - Role of the receptor-mediated apoptosis in Helicobacter pylori in gastric
      epithelial cells.
AB  - BACKGROUND AND AIMS: Two major pathways leading to apoptosis have been described.
      It has been shown that Helicobacter pylori-mediated apoptosis is mainly effected
      through the mitochondrial pathway (type II). The role of the type I pathway,
      including the death receptors, has been discussed controversially. Therefore, we
      investigated the role of Fas ligand (FasL) and TRAIL in H. pylori-mediated
      apoptosis by overexpressing antiapoptotic proteins in the human gastric
      epithelial cell line AGS. METHODS: AGS cells overexpressing the antiapoptotic
      proteins dnFADD, CrmA and Bcl-2 were generated. Apoptosis induced by Fas and H.
      pylori was monitored by histone ELISA. To investigate the role of TRAIL-mediated
      apoptosis, AGS cells were transduced with antisense constructs against the
      proapoptotic TRAIL receptors DR4 and DR5. Protein expression of Fas, TRAIL, DR4,
      and DR5 was analyzed by Western blot. RESULTS: Fas and H. pylori-mediated
      apoptosis was significantly inhibited in all generated cell lines, mainly in
      cells overexpressing CrmA and Bcl-2 with equal effectiveness. In the presence of
      H. pylori, TRAIL ligand and DR5 receptor were continuously expressed whereas DR4
      expression was increasing time dependently. TRAILDR5 antisense significantly
      reduced H. pylori-mediated apoptosis. CONCLUSIONS: H. pylori-mediated apoptosis
      is characterized by activation of either type I or type II pathway. Caspase-8
      plays an important role since it triggers the Type II pathway. Fas and TRAIL play
      an important role in the H. pylori-mediated apoptosis.

PMID- 15557764
TI  - Autoimmune hepatitis--sequel of a relapsing hepatitis A in a 75-year-old woman.
AB  - Acute hepatitis A virus (HAV) infection is a global cause of acute hepatitis.
      However, chronic HAV infection is unlikely. Nevertheless, there is some evidence
      that acute infection with HAV may trigger chronic active hepatitis which fulfils
      the criteria of autoimmune hepatitis (AIH). Whether AIH following HAV infection
      is virus specific remains unclear. Despite evidence that inherited factors may
      play a role in the development of autoimmunity after viral infection, the
      pathomechanism remains unclear. We describe a 75-year-old woman with a history of
      pulmonary sarcoidosis who developed AIH after acute HAV infection.

PMID- 15557765
TI  - Treatment with fluvastatin rapidly modulates, via different pathways, and in
      dependence on the baseline level, inflammation in hemodialysis patients.
AB  - BACKGROUND: Hemodialysis (HD) patients are frequently in an elevated inflammatory
      state which is correlated to the atherosclerosis-related and overall morbidity
      and mortality in this population. Statins, beyond their antilipidemic effects,
      are also considered to have anti-inflammatory, immunomodulating and antioxidant
      properties. The individual response of HD patients to a short course of
      fluvastatin, the mechanisms involved in the immunomodulating and anti
      inflammatory effects of this drug and the time interval to the appearance of
      these effects are investigated in this longitudinal study. METHODS: In a group of
      51 HD patients, fluvastatin 40 mg/day was administered for 4 weeks. Serial
      measurements of the lipid profile, C-reactive protein (CRP), interleukin-6 (IL
      6), soluble IL-6 receptor (sIL-6R), interleukin-10 (IL-10), and serum oxidized
      LDL (ox-LDL), were performed before, during, and after the treatment period.
      RESULTS: Total cholesterol was significantly reduced after 14 days of treatment
      with fluvastatin (from mean +/- SD 216.7 +/- 34.3 to 179.2 +/- 42.3 mg/dl, p <
      0.001). IL-6 and ox-LDL were reduced on day 28 (p < 0.001 and p < 0.01,
      respectively) and IL-10 was increased on day 14 (p = 0.05); CRP did not change
      significantly during the treatment period while sIL-6R was increased on day 28 of
      fluvastatin administration (p < 0.05). In a subgroup of patients with CRP, IL-6,
      sIL-6R, and ox-LDL baseline serum values > or = the median and IL-10 < or = the
      median, CRP was reduced on day 28 of fluvastatin treatment (p < 0.01), IL-6 and
      ox-LDL were reduced earlier, on day 14 (p = 0.05 and p < 0.05, respectively)
      while sIL-6R did not change significantly during the treatment period.
      CONCLUSIONS: Treatment with fluvastatin rapidly modulates inflammation in HD
      patients. Enhancement of anti-inflammatory mechanisms and attenuation of the
      inflammatory and oxidative state contribute to this modulation. Patients in an
      elevated baseline inflammatory state respond more rapidly and effectively to the
      treatment. This immediate and multi-potent action of the statins could be
      clinically useful in acute atherosclerosis complications or in the treatment of
      chronic inflammation in HD patients.

PMID- 15557766
TI  - Parietal lobe epilepsy: surgical treatment and outcome.
AB  - OBJECTIVE: Parietal lobe epilepsy (PLE) is neither common nor easily diagnosed
      because of its variable clinical features. To elucidate its characteristics and
      surgical outcome, the authors reviewed their surgical experiences. METHODS:
      Between September 1994 and August 2001, 38 patients with PLE received surgical
      treatment at the Seoul National University Hospital. All patients underwent
      resection, mainly involving the parietal lobe. RESULTS: Preoperatively, over 60%
      of the cases were not considered to be PLE, even though PLE was the most common
      diagnosis (15/38, 39.8%). An invasive study was performed in 37 of the 38
      patients. Awake operations under regional anesthesia were performed in 20
      patients (52.6%). Seizure disappeared in 15 (Engel's classification I, 39.5%),
      and rare seizure remained in 5 (Engel II, 13.2%). Thirteen patients showed a
      worthwhile improvement (Engel III, 34.2%), whereas 5 exhibited no worthwhile
      improvement (Engel IV, 13.2%). Pathologies were diverse, the most common being
      cortical dysplasia (94.3%). CONCLUSION: Since PLE is difficult to diagnose
      preoperatively, an invasive study covering the parietal lobe is mandatory, if PLE
      is suspected. Cortical dysplasia was the most common etiology, thus awake
      operation under regional anesthesia and intraoperative brain mapping is helpful
      during extensive resection in order to spare the eloquent cortex.

PMID- 15557767
TI  - Aphasia and thalamotomy: important issues.
AB  - Patients may present with classical symptoms suggesting aphasia following
      thalamotomy (repetition, comprehension, fluency and naming abnormalities). They
      may also present with 'freezing of speech', and this symptom should not be
      considered as a speech disorder or a symptom of Parkinson's disease progression,
      without careful testing to rule out language deficits, particularly dysfluency.
      There are important issues related to all language complications of thalamotomy,
      including (1) the time course of problems following surgery, (2) the impact of
      preexistingspeech problems, (3) the importance of the size and location of
      lesions, (4) the potential circuits important in the pathogenesis of a thalamic
      language disturbance and (5) whether laterality makes a difference (left- versus
      right-sided thalamic lesions). As more centers switch from thalamotomy to deep
      brain stimulation, the issues regarding aphasia will need to be addressed.

PMID- 15557768
TI  - Deep brain stimulation for Parkinson's disease: association between stimulation
      parameters and cognitive performance.
AB  - Chronic subthalamic nucleus stimulation produces inconsistent patterns of
      cognitive change in Parkinson's disease patients. Individually tailored
      stimulation parameters may contribute to this variable pattern of change.
      Systematic variation of amplitude, pulse width, and rate of stimulation has been
      reported to produce unique changes in motor and limbic response. To evaluate the
      association between stimulation parameters and cognitive/behavioral response,
      neuropsychological performance and stimulation parameter data of 8 Parkinson's
      disease patients were submitted to Pearson r correlation analysis. Results
      indicate that each stimulation parameter was significantly associated with a
      subset of measures. The current findings raise the possibility that adverse
      cognitive/behavioral responses may be treated through parameter modification
      while maintaining motor symptom efficacy.

PMID- 15557769
TI  - The significance of tumor location for Gamma Knife treatment of meningiomas.
AB  - We conducted this retrospective review to evaluate the influence of tumor
      location on the outcome of Gamma Knife treatment (GKT) for meningiomas. Patient
      charts from 1995 to 2001 of the Gamma Knife Center Zurich, Switzerland, were
      reviewed. Of 81 patients, 23% had parasagittal or convexity meningiomas (PCM),
      62% had skull base meningiomas (SBM), and 15% had posterior fossa meningiomas
      (PFM). Tumor control was achieved in 95% of PCM, 92% of SBM, and 100% of PFM.
      Neurological deficits were present in 5% of patients with PCM before and
      following GKT, in 62% of patients with SBM before GKT and in 46% following GKT,
      and in 17% of patients with PFM before and following GKT. We conclude that tumor
      location has an influence on tumor control and outcome. Deep and small tumors
      seem to be associated with better tumor control and less complications.
      Neurological deficits tend to resolve in deep tumors following GKT.

PMID- 15557770
TI  - TNF-inhibitors in Wegener's granulomatosis.

PMID- 15557771
TI  - Long-term evaluation of neuromyopathy in live donor FMF amyloidotic kidney
      transplant recipients.
AB  - BACKGROUND: Neuromyopathy was reported to be a problem among live donor familial
      Mediterranean fever (FMF) amyloid kidney transplant recipients. We aimed to
      address this issue on a long-term basis. METHODS: 14 FMF amyloid live donor
      kidney transplant recipients with a mean post-transplant follow-up period of
      82.43 +/- 50.1 months in comparison to a control group of 19 non-amyloid renal
      transplant patients were subjected to thorough neurological examination,
      laboratory and electrophysiologic studies. RESULTS: Both groups were comparable
      with regard to mean serum creatinine levels cyclosporine doses (p > 0.05),
      however trough cyclosporine levels were significantly lower in the amyloidotics
      than the controls (p = 0.04). Serum creatine phosphokinase was comparable in both
      groups (p = 0.59). The amyloid patients showed significantly increased polyphasic
      motor unit potentials and abnormal interference patterns in the biceps brachii
      muscle (p = 0.03) and the abductor polices brevis muscle (p = 0.05). Multivariate
      analysis showed a significant level for biceps myopathy in amyloidotics (p =
      0.001). Both groups attained no difference with regard to median nerve conduction
      velocity. CONCLUSION: Electrophysiologically evidenced neuromyopathy is more
      liable to occur in long-term live donor FMF amyloidotic kidney transplant
      recipients than in the other non-amyloidotic kidney transplant recipients even
      with no clinical manifestations or high creatine phosphokinase levels.

PMID- 15557772
TI  - Changes in voice and subjective sensations during a 45-min vocal loading test in
      female subjects with vocal training.
AB  - Twenty-four females (mean age 38 years) with varying amounts of vocal training
      read aloud from a book for 45 min (70 dB at 40 cm distance). Symptoms of the
      throat and voice were ascertained with a questionnaire before, during and after
      the test. Fundamental frequency (F(0)) and sound pressure level (SPL) were
      measured. The alpha ratio describing the spectrum slope was calculated: SPL in
      the range 1-5 kHz minus SPL in the range 50 Hz-1 kHz. All measurements were made
      for the 1st, 5th, 15th, 30th and the 45th min of loading and for text reading
      before and after it. F(0), SPL and alpha values rose during the test, which may
      indicate adaptation to loading. During the first 5 min, however, these parameters
      showed a decreasing tendency, possibly reflecting warm-up. Subjects with more
      vocal training had a lower F(0) in the loading test. SPL seemed to reflect
      variation of symptoms during loading. Changes in acoustic parameters did not
      distinguish between subjects with most and fewest symptoms of fatigue in this
      test.

PMID- 15557773
TI  - The perception of speech naturalness of post-therapeutic and altered auditory
      feedback speech of adults with mild and severe stuttering.
AB  - The effect of therapy and altered auditory feedback (AAF) on the perception of
      speech naturalness of people who stutter was examined. Thirty-five naive young
      adult listeners rated speech samples from fluent speakers and individuals who
      stutter. Samples came from normal adults who spoke Standard American English;
      adults with mild or severe stuttering who spoke under conditions of non-altered
      feedback (NAF), delayed auditory feedback (DAF), and frequency-altered feedback
      (FAF); and adults with mild or severe stuttering prior to and following
      successful completion of a Precision Fluency Shaping Program. Speech produced
      under AAF was rated as significantly more natural sounding than speech from the
      same individuals under NAF (p < 0.0001). Speech produced during FAF was judged to
      be more natural sounding than that produced during DAF for those with mild (p =
      0.003) and severe (p < 0.0001) stuttering. Mild stuttered speech was judged to
      have more natural-sounding speech than severe stuttered speech during AAF (p <
      0.0001). Speech from individuals following therapy was rated significantly less
      natural sounding than that from individuals during AAF for both mild and severe
      stuttering (p < 0.0001). The speech of individuals prior to therapy was rated
      significantly more natural than their speech produced after therapy (p < 0.0001).
      Speech from normal fluent speakers was rated as significantly more natural
      sounding than all samples produced from the individuals who stutter (p < 0.0001).
      These findings support the contention that AAF benefits those who stutter through
      a reduction of stuttering with a gain in perceived speech naturalness.

PMID- 15557774
TI  - Disfluency in Tourette syndrome: observational study in three cases.
AB  - It is often stated that stuttering is a common speech disorder in individuals
      with Tourette syndrome (TS). It has also been suggested, however, that the
      fluency failures observed in people with TS do not completely conform to the
      classic pattern of stuttering. The present paper describes the results of an
      analysis of the speech patterns of three individuals with TS. A picture emerged
      that bears some resemblance to stuttering, cluttering, and palilalia but that is
      also different from each of these disfluency types.

PMID- 15557775
TI  - Acoustic analysis of speech tasks performed by three individuals with
      spinocerebellar ataxia.
AB  - A number of speech tasks produced by three female subjects with different types
      of genetically diagnosed spinocerebellar ataxia and with mild dysarthria were
      investigated using acoustic instrumentation. All subjects showed a number of
      signs of decreased speech rate, increased pause duration, increased and more
      variable durations of alternating motion rate, sequential motion rate syllables
      and inter-stress intervals in addition to vocal instability. These signs were
      consistent with the perceptual judgment of ataxic dysarthria. Furthermore, the
      severity of impairment found using these speech analysis methods seemed to
      correspond to the general severity of the disease and the duration of the illness
      in these few subjects. The tasks studied appeared to be relevant and suitable for
      acoustic analyses as they did reveal deviations in the speech of the subjects
      compared with controls.

PMID- 15557776
TI  - A study of pegylated liposomal Doxorubicin in platinum-refractory epithelial
      ovarian cancer.
AB  - OBJECTIVES: The purposes of this study were to determine the efficacy of
      pegylated liposomal doxorubicin (PLD), using a dose of 40 mg/m2 given every 3
      weeks, in the treatment of platinum-refractory epithelial ovarian cancer (EOC)
      and to evaluate the toxicities. METHODS: Fourteen patients with platinum
      resistant EOC were treated with intravenous PLD 40 mg/m2 every 3 weeks. Tumor
      responses were assessed every 2-3 cycles by CT scan. RESULTS: All 14 patients
      were evaluable for toxicity, but only 13 patients were evaluable for response
      because 1 patient who had grade 3 palmar-plantar erythrodysesthesia (PPE) refused
      to continue with the treatment. Three partial responses were observed in 13
      patients. The overall response rate was 23% (95% confidence interval 10-38%). The
      median time to response was 2 months, and the median duration of response was 3
      months. The median survival of the 13 patients was 14.5 months, and the median
      progression-free survival was 6 months. In this study, we had only 4 cases of
      grade 3 toxicity (2 cases of grade 3 leukopenia and 2 cases of grade 3 PPE). All
      toxicities that occurred were manageable. CONCLUSION: This is the first report of
      the use of a slightly modified dose schedule for PLD at a dose of 40 mg/m2 every
      3 weeks, which is active in platinum-refractory EOC with manageable toxicities.

PMID- 15557777
TI  - Tissue levels of WR-1065, the active metabolite of amifostine (Ethyol), are
      equivalent following intravenous or subcutaneous administration in cynomolgus
      monkeys.
AB  - Amifostine (Ethyol) is a cytoprotective drug approved for the reduction of
      xerostomia in head and neck cancer when administered to patients receiving
      postoperative radiation therapy. Although amifostine is approved for intravenous
      infusion, the off-label subcutaneous route of administration has become more
      prevalent. Although human patient data indicate higher plasma bioavailability of
      the active metabolite (WR-1065) following intravenous compared to subcutaneous
      administration, there are no corresponding data showing human tissue levels of WR
      1065 following either route of administration due to the difficulty in obtaining
      human specimens. In our study we compared plasma and tissue pharmacokinetics of
      WR-1065 in primates following both routes of administration. Monkeys received
      amifostine at a dose of 260 mg/m2 either intravenously or subcutaneously. Plasma
      samples were analyzed for total WR-1065 by reverse-phase high-pressure liquid
      chromatography (HPLC) and fluorescence detection up to 4 h after amifostine
      administration. Tissues were analyzed for free WR-1065 by reverse-phase HPLC and
      electrochemical detection 30 and 60 min after administration. Following
      intravenous administration, plasma WR-1065 levels peaked rapidly and showed a bi
      exponential decline, while following subcutaneous administration WR-1065 levels
      rose slowly and declined exponentially. The relative plasma bioavailability of WR
      1065 given subcutaneously was lower at 30 and 60 min. Interestingly, after 30
      min, tissues showed equal or slightly greater concentrations of WR-1065 following
      subcutaneous administration. Levels following 60 min were comparable following
      both routes. The plasma bioavailability studies performed in primates confirm
      human plasma data. Expanding the study to evaluate primate tissue levels of WR
      1065 revealed that despite lower plasma bioavailability following subcutaneous
      administration, tissue levels of the active metabolite were surprisingly greater
      than or equal to those measured in animals that received the drug intravenously.
      These studies strengthen the argument for subcutaneous administration of
      amifostine in radiation oncology.

PMID- 15557778
TI  - Predictors of delayed therapy after expectant management for localized prostate
      cancer in the era of prostate-specific antigen.
AB  - OBJECTIVE: To identify risk factors for delayed cancer-directed intervention in
      modern era prostate cancer patients who initially elect expectant management.
      MATERIALS AND METHODS: An observational, cohort study of expectantly managed
      patients, diagnosed with clinical T(1-4)NxM0 prostate cancer between 1993 and
      2000 was carried out. Data including TNM stage, age, serum prostate-specific
      antigen (PSA), prostate gland volume by transrectal ultrasound, Gleason score,
      percent biopsies positive for cancer, imaging results, initial treatment
      selection, and outcome data were collected on all patients. RESULTS: 192 of 561
      patients (34.3%) elected expectant management, and follow-up data were available
      for 187 (97.4%) patients. With a median follow-up of 3.6 years, 90 (48.1%)
      patients had a cancer-directed intervention. Gleason score (p = 0.0097) and
      percent of positive biopsy cores (p = 0.03) were independent predictors of time
      to intervention. As expected, PSA doubling time became the most significant
      predictor of intervention (p = 0.0057) when added to the model. These independent
      covariates are able to characterize low-, intermediate- and high-risk groups for
      cancer-directed intervention. CONCLUSIONS: Cancer-directed intervention is common
      in patients who choose expectant management in the PSA era. Gleason score and
      percent of positive biopsy cores predict cancer-directed interventions, thus,
      these patients may be least suitable for expectant management.

PMID- 15557779
TI  - Greek M.D. Anderson Symptom Inventory: validation and utility in cancer patients.
AB  - OBJECTIVE: The M.D. Anderson Symptom Inventory (MDASI) is a brief assessment of
      the severity and impact of cancer-related symptoms. The purpose of this study was
      the translation and validation of the questionnaire in Greek (G-MDASI). METHODS:
      The translation and validation of the assessment took place at a Pain Relief and
      Palliative Care Unit. The final validation sample included 150 cancer patients
      (61 males, 89 females, age range 31-88 years, mean age 63.32). The patients
      completed the questionnaires at the outpatient clinic. Assessing the validity and
      reliability constituted the actual validation of the G-MDASI. RESULTS: The item
      'diarrhea' had a score of 0 in 139 patients and, thus was omitted from the 'core'
      list. Consequently, the core questionnaire consisted of 14 items. Factor analysis
      resulted in a 3-factor model, in both validation and cross-validation samples.
      The examination of the sensitivity of the MDASI revealed that there were
      differences between patients with poor-to-good performance status but no
      differences were found between patients in different treatment groups.
      CONCLUSIONS: The results showed that the G-MDASI is a reliable and valid measure
      in Greek cancer patients. It has proved to be a comprehensive symptom assessment
      tool.

PMID- 15557780
TI  - Testicular lymphoma: organ-specific treatment did not improve outcome.
AB  - OBJECTIVES: To assess whether the use of an organ-specific treatment could
      improve event-free survival (EFS) and overall survival as endpoints in testicular
      lymphoma in the early stage: IE and IIE. METHODS: Thirty-four patients were
      selected to be treated with orchiectomy following six cycles of anthracycline
      based combined chemotherapy and radiotherapy (scrotum and contralateral testis in
      stage IE, contralateral testis and lymph nodes in stage IIE). Prophylaxis to the
      central nervous system was administered with four monthly cycles of a high dose
      of methotrexate: 6 g/m2. RESULTS: Complete response was achieved in 33 cases
      (97%). However, relapses continue to be the rule; at a median follow-up of 74
      months (range 61-120), 21 patients relapsed. Thus, actuarial curves at 5 years
      were 32% for EFS and 30% for overall survival, because all patients with failure
      and relapse died of tumor progression. Relapses were observed in uncommon sites:
      lung, bone marrow and as disseminate disease; no relapses were observed in
      irradiated sites of the central nervous system. CONCLUSIONS: Testicular lymphomas
      remain a problem as regards defining the optimal treatment. The use of a specific
      treatment based on organ-involved sites did not show any improvement in outcome.
      It is evident that more specific therapies need to be explored.

PMID- 15557781
TI  - Phase I study of hyperfractionated radiation therapy with protracted 5
      fluorouracil infusion in patients with locally advanced pancreatic cancer.
AB  - OBJECTIVE: This study investigated the maximum-tolerated dose of
      hyperfractionated radiation therapy with protracted 5-fluorouracil (5-FU)
      infusion in patients with locally advanced, unresectable pancreatic cancer.
      METHODS: Five cohorts of patients were scheduled to receive escalating doses of
      hyperfractionated radiation therapy (range, 45.6-64.8 Gy). All patients received
      two fractions of 1.2 Gy each (separated by 6 h) per day for 5 days a week, and
      received protracted 5-FU infusion (200 mg/m2/day) during the radiation course.
      The maximum-tolerated dose was defined as one dose level below the dose at which
      more than one third of 3-6 patients experienced dose-limiting toxicity. RESULTS:
      Twenty-nine patients were enrolled in this study. The most common toxicities were
      nausea/vomiting and anorexia. Although 1 patient developed bleeding from a
      gastric ulcer 3 months after the completion of chemoradiotherapy, the maximum
      tolerated dose was not reached even at the highest dose level (level 5, 64.8 Gy).
      The median survival time was 12.2 months and the 1-year survival rate was 55.0%.
      CONCLUSION: The toxicity associated with our regimen was tolerable up to dose
      level 5 (64.8 Gy). We are currently conducting a phase II study of this
      hyperfractionated radiation therapy with protracted 5-FU infusion at a dose of
      64.8 Gy.

PMID- 15557782
TI  - 5-fluorouracil leucovorin and oxaliplatin (FOLFOX) in the treatment of metastatic
      colon cancer with severe liver dysfunction.
AB  - Colon cancer patients with severe hepatic dysfunction secondary to liver
      metastases have limited treatment options. 5-Fluorouracil (5-FU) infusional
      therapy has been attempted, but data suggesting significant clinical benefit are
      lacking. Although both 5-FU and oxaliplatin have been well tolerated as single
      agents in patients with severe hepatic dysfunction, the combination of these
      drugs in this setting has not been investigated. We report on three patients with
      severe liver dysfunction secondary to metastatic colon cancer treated with a
      combination of 5-FU, oxaliplatin, and leucovorin (FOLFOX). All three patients
      tolerated chemotherapy well without any significant toxicity. Liver function
      tests improved within 2 weeks from the start of treatment. Clinical outcomes
      consisted of two partial responses and one disease stabilization. Two patients
      progressed after 4 and 7 months from FOLFOX initiation while treatment is ongoing
      in the third patient. FOLFOX chemotherapy is feasible and can be associated with
      positive outcomes in patients with metastatic colon cancer and severe hepatic
      dysfunction. This regimen should be investigated further in similar clinical
      settings.

PMID- 15557783
TI  - Association between components of the insulin-like growth factor system and
      epithelial ovarian cancer risk.
AB  - BACKGROUND: Components of the insulin-like growth factor (IGF) system have been
      associated with several cancers, but very few studies are available for ovarian
      cancer. METHODS: A case-control study conducted between 1999 and 2003 in Italy,
      including a total of 59 women with incident, histologically confirmed ovarian
      cancer and 108 controls admitted to the same hospital network as cases, for acute
      non-neoplastic diseases. All subjects were interviewed using a validated
      questionnaire. RESULTS: After adjustment for potential confounders, the
      multivariate odds ratios for the highest versus the lowest tertile of various IGF
      components were 0.6 (95% confidence interval, CI: 0.2-1.4) for free IGF-I, 0.4
      (CI: 0.1-1.5) for total IGF-I, 2.6 (CI: 0.9-6.9) for IGF-binding protein (IGFBP)
      1, and 0.2 (CI: 0.0-0.6) for IGFBP-3. CONCLUSIONS: This study suggests a
      protective role of IGFBP-3 and a positive association of IGFBP-1 with ovarian
      cancer. The complex role of the IGF system in ovarian carcinogenesis deserves
      further clarification.

PMID- 15557784
TI  - Clinical perspective on desmoplastic small round-cell tumor.
AB  - Rare diseases are often associated with uninformed medical decisions and poorly
      executed treatments because of inexperience of the physicians. Desmoplastic small
      round-cell tumor is a rare disease that is a form of peritoneal surface
      malignancy usually affecting young males, with a mean survival of 29 months. In
      order to begin to build a more knowledgeable clinical pathway all 7 patients
      treated at the Washington Hospital Center were studied and compared to patients
      described in the medical literature. Clinical and pathological data, tumor
      distribution, cytoreductive surgery, completeness of cytoreduction and survival
      were recorded and analyzed. The first most common symptoms were pain, increased
      abdominal girth and palpable abdominal mass in our patients and in the literature
      review. The overall survival did not improve with cytoreductive surgery plus
      intraperitoneal chemotherapy (mean survival 32 months); however, 2 long-term
      survivors who responded to systemic chemotherapy of 55 and 101 months were
      recorded. The latter may be the longest survivor reported in the literature. No
      consistent response to chemotherapy was observed in our patients or in any
      literature review. Complete surgical removal of this malignancy did not correlate
      with survival in our patients. The absence of improved survival of our
      aggressively treated patients as compared to the literature was thought to be a
      consequence of an advanced stage of the disease. A new comprehensive approach
      that uses complete clearing of cancer by surgery and perioperative systemic and
      perioperative intraperitoneal chemotherapy as early as is possible in the natural
      history of the disease emerged as goals for future management.

PMID- 15557785
TI  - Phase II study of pegylated liposomal doxorubicin in heavily pretreated
      epithelial ovarian cancer patients. May a new treatment schedule improve toxicity
      profile?
AB  - OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has shown promising activity in
      the treatment of recurrent ovarian cancer but skin toxicity remains the dose
      limiting toxicity of the drug. The aim of this study was to investigate whether a
      different treatment schedule may improve the toxicity profile, especially in
      terms of dermatological and mucosal toxicity. METHODS: It is an open-label phase
      II study in a population of heavily pretreated ovarian cancer patients. PLD was
      administered at the dose of 35 mg/m2 q21 until disease progression or
      unacceptable toxicity. RESULTS: Thirty-seven heavily pretreated (median number of
      previous chemotherapy regimens 2, range 1-6) ovarian cancer patients were
      enrolled. All patients received at least two courses of chemotherapy and all were
      evaluated for response. No one showed complete response, while five partial
      responses (13.5%), 16 stabilizations of disease (48.6%) and 14 progressions of
      disease (37.8%) were observed. The median time to response was 12 weeks (range 8
      16). The median duration of response was 22.8 weeks (range 4-68), the median
      duration of stabilization of disease was 17.6 weeks (range 4-28). Palmar plantar
      erythrodysesthesia (PPE) occurred in 8 patients (21.6%) and was of grade 3 in one
      patient (2.8%). Grade 1 stomatitis occurred in 3 patients (8.1%). Grade 3-4
      neutropenia occurred in only 4 patients (10.8%). CONCLUSIONS: PLD at the dose of
      35 mg/m2 q21 seems to translate into an acceptable skin toxicity profile with a
      response rate comparable to others obtained with a standard schedule.

PMID- 15557786
TI  - Front-line chemotherapy with docetaxel and gemcitabine administered every two
      weeks in patients with metastatic breast cancer: a multicenter phase II study.
AB  - OBJECTIVE: To evaluate the docetaxel-gemcitabine combination administered every 2
      weeks in women with untreated metastatic breast cancer (MBC). METHODS: Fifty-two
      patients with MBC received docetaxel 65 mg/m2 as front-line chemotherapy
      intravenously over 1 h followed by gemcitabine 1,500 mg/m2 intravenously over 30
      min on days 1 and 14. Cycles were repeated every 28 days without prophylactic
      growth factor support. Twenty-eight (54%) patients had previously received
      chemotherapy as adjuvant or neoadjuvant treatment. Thirty-six (69%) patients had
      visceral disease including 20 (38%) with liver metastases. All patients were
      evaluated for toxicity and 45 for response. RESULTS: In an intention-to-treat
      analysis, a complete response occurred in 7 (13%) patients and partial response
      in 24 (46%) for an overall response rate of 59% (95% CI: 46.3-73.0%). The
      response rate was 68% for the 28 patients who had previously received adjuvant or
      neoadjuvant chemotherapy and 67% for the 36 patients with visceral metastases.
      The median duration of response was 6.1 months and the median time to disease
      progression 10.9 months. A total of 254 cycles were administered with dose
      reduction in 26 (10%) cycles and no lethal toxicity. Grade III-IV neutropenia
      occurred in 17 (33%) patients and thrombocytopenia in 3 (6%). Febrile neutropenia
      developed in 3 (6%) patients. Nonhematological toxicity was generally mild.
      CONCLUSION: The docetaxel-gemcitabine combination is an active and well-tolerated
      front-line treatment for patients with MBC. This regimen represents a suitable
      option especially for women relapsing after anthracycline-based adjuvant
      chemotherapy.

PMID- 15557787
TI  - Weekly combination of docetaxel and vinorelbine in metastatic breast cancer: a
      phase I/II study.
AB  - OBJECTIVE: A phase I/II study was carried out to determine the recommended dose
      (RD) and to assess the efficacy and safety of a weekly docetaxel-vinorelbine
      combination in advanced breast cancer (ABC) patients. METHODS: Twenty-four female
      patients with histologically proven ABC received intravenous vinorelbine (20 min)
      followed by intravenous docetaxel (1 h) on days 1, 8 and 15 of a 4-week cycle.
      Starting doses were 20 mg/m2 docetaxel and 15 mg/m2 vinorelbine. RESULTS:
      Patients had a median age of 62 years (range 38-74 years), and 92% had
      performance status 0-1. The most common sites of metastases were the lungs (32%),
      liver (29%) and bone (14%). Seventy-one percent of patients had received prior
      chemotherapy. The RDs of docetaxel and vinorelbine were 20 and 15 mg/m2,
      respectively. Dose-limiting toxicities were neutropenia-induced dose delay and
      febrile neutropenia. The response rate at the RD was 43%. All responses were seen
      in non-pretreated patients. Grade 3-4 neutropenia occurred in 80% of patients, 3
      of whom experienced febrile neutropenia and died as a possible consequence of
      neutropenia. CONCLUSION: This docetaxel-vinorelbine combination as first-line
      therapy yields a response rate similar to that of single-agent docetaxel as
      second-line therapy. However, given the high rate of myelotoxicity, higher doses
      are not feasible.

PMID- 15557788
TI  - The prognostic relevance of fascin expression in human gastric carcinoma.
AB  - OBJECTIVE: Fascin, an actin-bundling protein that is found in membrane ruffles,
      microspikes, and stress fibers, induces membrane protrusions and increases cell
      motility in various transformed cells. The expression of fascin in epithelial
      neoplasms has been described only recently, and its role in gastric cancer is
      still unknown. METHODS: Paraffin sections of gastric carcinoma from 214 patients
      were immunohistochemically investigated using monoclonal antifascin antibody.
      Staining more than 5% of tumor cells was recorded as positive immunoreactivity.
      RESULTS: Overall, fascin immunoreactivity was detected in 54 out of a total of
      214 patients (25%). 26 patients were classified as 1+ (5-25% immunoreactive tumor
      cells) and 28 were 2+ (>25%). In these patients, 7 tumors showed high (>75%)
      fascin immunoreactivity. Increased immunoreactivity of fascin was sometimes seen
      at the edge of the tumor. Fascin immunoreactivity was increased according to the
      extent of primary tumor (p = 0.026). Fascin expression was correlated with age (p
      = 0.005), serosal invasion (p = 0.013), positive lymph node metastasis (p =
      0.006), histopathological grading (p = 0.019), TNM stage (p = 0.003) and
      recurrence (p = 0.006); however, it was not correlated with distant metastasis (p
      = 0.108), Lauren's type (p = 0.205), or R classification (p = 0.056). Among 166
      patients with T1, T2, T3 or T4, those with fascin-positive tumors had a
      significantly poorer prognosis than those with fascin-negative tumors (p =
      0.029). Multivariate analysis showed that fascin expression was not an
      independent poor prognostic factor. CONCLUSION: Our findings suggest that the
      immunohistochemical detection of fascin could provide useful information as one
      of the prognostic factors in gastric cancer patients.

PMID- 15557789
TI  - Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-12 in
      gastric and colonic cancer cell lines and in human colorectal cancer.
AB  - OBJECTIVE: The expression of UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase-12 (pp-GalNAc-T12) was studied in 3 normal human
      tissues (stomach, small intestine and colon), 3 stomach and 6 colon cancer cell
      lines, as well as in the resected cancer tissues and normal tissues (control)
      from 19 patients with colorectal cancer. METHODS: Marathon Ready cDNAs were used
      as the templates of normal tissues. mRNA was extracted from the cell lines and
      resected tissues, and reverse-transcribed to cDNA. The expression of pp-GalNAc
      T12 was determined with a real-time polymerase chain reaction (PCR). RESULTS: It
      was found that the expression of pp-GalNAc-T12 was strong in 3 normal tissues,
      weak or negligible in 9 cancer cell lines, and down-regulated in all of the
      colorectal cancer tissues as compared with normal control samples. Moreover, the
      expression of pp-GalNAc-T12 tended to inversely correlate with the TNM stage, and
      statistically was much lower in the samples with metastasis than in those
      without. However, the expression in the tissues did not correlate with the
      concentration of serum CA 19-9 routinely applied in the diagnosis and assessment
      of prognosis in patients with colonic cancers. CONCLUSION: the expression of pp
      GalNAc-T12 seems to be a negative marker especially of metastatic gastric and
      colorectal cancer.

PMID- 15557790
TI  - Expression profiles of a human pancreatic cancer cell line upon induction of
      apoptosis search for modulators in cancer therapy.
AB  - We analyzed the differential gene expression in the pancreatic cancer cell line
      NP-18 upon induction of apoptosis caused by cyclin-dependent kinase inhibition
      triggered by either overexpression of the tumor suppressor gene p16(INK4A)using
      an adenoviral construction or incubation with the chemical inhibitors,
      roscovitine or olomoucine. Screening was performed using cDNA arrays from
      Clontech that allowed the determination of the expression of 1,176 genes
      specifically related with cancer. The analysis was carried out using the Atlas
      Image 2.01 (Clontech) and GeneSpring 4.2 (Silicon Genetics) softwares. Among the
      differentially expressed genes, we chose for further validation histone
      deacetylase 1 (HDAC1), von Hippel Lindau and decorin as upregulated genes, and
      Sp1, hypoxia-inducible factor-1 alpha and DNA primase as downregulated genes. The
      changes in the expression of these genes to mRNA were validated by quantitative
      RT-PCR and the final translation into protein by Western blot analysis.
      Inhibition of HDAC activity, Sp1 binding and DNA primase expression led to an
      increase in the level of apoptosis, both in parental cells and in doxorubicin
      resistant cells. Therefore, these proteins could constitute possible targets to
      develop modulators in cancer chemotherapy that would increase or restore
      apoptosis.

PMID- 15557791
TI  - Cyclin E amplification and overexpression in clear cell adenocarcinoma of the
      ovary.
AB  - OBJECTIVE: The purpose of this study is to compare DNA, mRNA and protein levels
      of the cyclin E between clear cell (CC) and serous (SC) ovarian carcinomas, and
      evaluate the relationship between cyclin E and p53 status. METHOD: We examined
      the DNA, mRNA and protein levels of cyclin E and the protein level of p53 in 44
      CCs and 39 SCs using microdissected tissues. RESULTS: Relative cyclin E mRNA
      expression was significantly higher in CC (3.62, 95% CI, 2.24-4.99) than in SC
      (1.75, 95% CI, 1.05-2.45; p = 0.0098). The percentage of positive nuclear
      staining of cyclin E was significantly higher in CC (48.3, 95% CI, 40.4-56.1)
      than SC (25.3, 95% CI, 17.4-33.3; p = 0.0001). The mRNA and protein expression of
      cyclin E was significantly correlated (r = 0.66, p < 0.0001). However, the
      correlation between relative DNA copy number and relative mRNA expression was not
      significant (r = -0.063; p = 0.66). Percentage of positive nuclear staining of
      cyclin E was significantly higher in p53 positive cases (51.8, 95% CI, 40.0-63.5)
      than p53 negative cases (36.2, 95% CI, 28.2-44.2; p = 0.028). CONCLUSIONS: Cyclin
      E expression is significantly higher in CC than in SC. Cyclin E expression is
      significantly related with p53 positivity.

PMID- 15557792
TI  - Prognostic significance of stromelysin-3 and tissue inhibitor of matrix
      metalloproteinase-2 in esophageal cancer.
AB  - OBJECTIVE: Stromelysins (matrix metalloproteinases: MMP-10 or ST-2 and MMP-11 or
      ST-3) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) have been
      shown to be associated with human tumor progression, invasion and metastasis. The
      aim of the present study was to determine the prognostic significance of these
      proteins in esophageal squamous cell carcinoma (ESCC). METHODS:
      Immunohistochemical analysis was carried out in 65 surgically resected ESCCs and
      49 distant histologically normal esophageal tissues and 16 cases of dysplasias.
      Statistical analyses were performed to determine the associations between the
      protein expression and clinicopathological parameters and survival of esophageal
      cancer patients. RESULTS: Expression of ST-2, ST-3, TIMP-1 and TIMP-2 was
      observed in 43/65 (66%), 51/65 (78%), 43/65 (66%) and 47/65 (72%) ESCC cases,
      respectively. Univariate analysis showed that TIMP-2 expression was associated
      with tumor site (OR = 2.63, p = 0.017). TIMP-1+/TIMP-2+ phenotype was inversely
      correlated with nodal invasiveness of the tumor (OR = 0.4, p = 0.04).
      Interestingly, p53 expression was associated with increased levels of ST-3 (OR =
      0.11, p = 0.02) and TIMP-1 (OR = 3.2, p = 0.007) suggesting possible involvement
      of p53 in the regulation of these proteins. An increased expression of ST-2, ST
      3, TIMP-1 and TIMP-2 was observed in 11/16 (69%), 7/17 (44%), 11/16 (69%) and
      8/16 (50%) dysplasias also suggesting that these alterations are early events in
      esophageal tumorigenesis. All the ESCC patients were followed up
      postesophagectomy for a maximum period of 59 months (mean disease-free survival =
      12 months). Kaplan-Meier survival analysis showed that patients with ST-3
      positive and TIMP-2-negative carcinoma had a significantly shorter disease-free
      survival (median disease-free survival time of 4 months) as compared to patients
      in the other groups (median disease-free survival time of 20 months; p = 0.0016).
      To our knowledge this is the first report showing that ST-3+/TIMP-2- phenotype
      remained of significant predictive value for disease-free survival (p = 0.0007)
      in multivariate analysis including a conventional clinicopathological factor,
      tumor stage (p = 0.051). CONCLUSION: Our results suggest that ST-3+/TIMP-2-
      phenotype is an adverse prognosticator in esophageal cancer patients.

PMID- 15557793
TI  - Involvement of ERK1/2 and p38 MAP kinase in doxorubicin-induced uPA expression in
      human RC-K8 lymphoma and NCI-H69 small cell lung carcinoma cells.
AB  - We previously demonstrated the doxorubicin-induced urokinase-type plasminogen
      activator (uPA) expression in human RC-K8 lymphoma cells and NCI-H69 small cell
      lung carcinoma cells in which reactive oxygen species might be involved. Western
      blotting analysis revealed phosphorylation/activation of mitogen-activated
      protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) 1/2,
      p38 MAP kinase and stress-activated protein kinase/c-jun N-terminal protein
      kinase (SAPK/JNK) in doxorubicin-treated RC-K8 and H69 cells, and, therefore, we
      attempted to identify the MAP kinases implicated in doxorubicin-induced uPA
      expression by the use of their specific inhibitors. U0126, SB202190 and JNKI-1,
      inhibitors for MAPK kinase, (MEK) 1/2, p38 MAP kinase and SAPK/JNK, respectively,
      specifically and clearly inhibited their corresponding kinases. U0126 and
      SB202190, but not JNKI-1, almost completely inhibited the doxorubicin-induced uPA
      expression in both RC-K8 and H69 cells. However, U0126 rather enhanced the
      doxorubicin-induced activation of caspase-3 and poly ADP-ribose polymerase
      (PARP), and U0126 itself activated caspase-3 and PARP. Interestingly, JNKI-1
      inhibited the doxorubicin-induced activation of caspase-3 and PARP. Therefore,
      doxorubicin treatment activates the above three kinases, but different MAP kinase
      signaling is responsible in the doxorubicin-induced caspase activation and
      expression of uPA. Thus, we could possibly manipulate the direction of
      doxorubicin-induced MAP kinase activation and the effects of doxorubicin on the
      tumor cell biology by the use of MAP kinase inhibitors.

PMID- 15557794
TI  - Hepatocellular carcinoma with intra-atrial tumor thrombi. A report of three cases
      responsive to thalidomide treatment and literature review.
AB  - BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), inferior
      vena cava/intra-right atrial (IVC/RA) tumor thrombi are not uncommon findings and
      are usually associated with extremely poor outcome. Surgical interventions as
      well as nonsurgical approaches, such as transcatheter arterial chemoembolization
      and radiotherapy, have been used in the treatment of patients with symptomatic
      IVC/RA tumor thrombi. However, such therapeutic modalities are usually not
      feasible when a patient shows poor general performance, the presence of
      metastatic disease, and underlying hepatic dysfunction. Such patients show
      limited survival. MATERIAL AND METHODS: Herein we describe 3 patients with
      advanced-stage HCC whose IVC/RA tumor thrombi and primary tumors regressed
      remarkably after low-dose thalidomide (200-400 mg/day) therapy. An Entrez PUBMED
      search of English Literature articles was performed to identify other cases of RA
      tumor thrombi in HCC who had received various treatments. RESULTS: Two of our
      patients survived for more than 15 months after the diagnosis of IVC/RA tumor
      thrombi, while the other had effective symptomatic palliation associated with a
      drastic fall of AFP serum levels and significant tumor regression within 4 weeks
      of thalidomide therapy. A literature review suggested that the survival of our
      patients is comparable with that of occasional patients who had received
      aggressive surgical intervention. CONCLUSIONS: Our results suggest that, despite
      the low tumor response rate in earlier studies, thalidomide therapy may sometimes
      provide effective palliation for patients with far advanced HCC with symptomatic
      IVC/RA tumor thrombi and who are not candidates for alternative treatment
      options.

PMID- 15557795
TI  - Preface: chromosomal instability and breast cancer pathogenesis.

PMID- 15557796
TI  - The genetic epidemiology of breast cancer genes.
AB  - Genetic susceptibility to breast cancer in women is conferred by a large number
      of genes, of which six have so far been identified. In the context of multiple
      case families, BRCA1 and BRCA2 are the most important. Mutations in these genes
      confer high lifetime risks of breast cancer and ovarian cancer, and more moderate
      risks of prostate cancer and some other cancer types. Mutations in the CHEK2 and
      ATM genes, by contrast, cause much more modest (2-4 fold) risks of breast cancer.
      Genes so far identified explain approximately 20% of the familial aggregation of
      breast cancer. The remaining susceptibility genes have, so far, proved illusive,
      suggesting that they are numerous and confer moderate risks. A variety of
      techniques including genome-wide association studies, use of quantitative
      intermediate endpoints, and resequencing of genes may be required to identify
      them. The identification of such genes can provide a basis for targeted
      prevention of breast cancer.

PMID- 15557797
TI  - BRCA1 and BRCA2 in breast cancer predisposition and recombination control.
AB  - Hereditary predisposition to breast and ovarian cancer is determined in large
      part by loss-of-function mutations in one of two genes, BRCA1 and BRCA2 . Early
      discoveries that the two genes function in the control of homologous
      recombination and the prevention of genomic instability have been strongly
      supported by subsequent work. Our aim here is to highlight new advances in the
      study of BRCA1 and BRCA2 , and to place these advances in the context of existing
      knowledge.

PMID- 15557798
TI  - ATM and genome maintenance: defining its role in breast cancer susceptibility.
AB  - The ATM gene is mutated in ataxia-telangiectasia (A-T), a genetic instability
      syndrome characterized by increased cancer risk, as well as other features.
      Recent studies have shown that the ATM protein kinase plays a critical role in
      maintaining genome integrity by activating a biochemical chain reaction that in
      turn leads to cell cycle checkpoint activation and repair of DNA damage. ATM
      targets include well-known tumor suppressor genes such as p53 and BRCA1, both of
      which play an important role in predisposition to breast cancer. Studies of A-T
      families have consistently reported an increased risk of breast cancer in women
      with one mutated ATM gene, but so far an increased frequency of ATM mutations has
      not been found in women with breast cancer. Some specific missense and protein
      truncating variants of ATM have been reported to confer increased breast cancer
      risk, but the magnitude of this risk remains uncertain. A more comprehensive
      analysis of ATM is needed in large case-control studies, and in multiple-case
      breast cancer families.

PMID- 15557799
TI  - Genetic and epigenetic changes in mammary epithelial cells may mimic early events
      in carcinogenesis.
AB  - Studies of human mammary epithelial cells from healthy individuals are providing
      novel insights into how early epigenetic and genetic events affect genomic
      integrity and fuel carcinogenesis. Key epigenetic changes, such as the
      hypermethylation of the p16 (INK4a) promoter sequences, create a previously
      unappreciated preclonal phase of tumorigenesis in which a subpopulation of
      mammary epithelial cells are positioned for progression to malignancy (Romanov et
      al. , 2001, Nature , 409:633-637; Tlsty et al. , 2001, J. Mammary Gland Biol.
      Neoplasia , 6:235-243). These key changes precede the clonal outgrowth of
      premalignant lesions and occur frequently in healthy, disease-free women.
      Understanding more about these early events should provide novel molecular
      candidates for prevention and therapy of breast cancer that target the process
      instead of the consequences of genomic instability. This review will highlight
      some of the key alterations that have been studied in human mammary epithelial
      cells in culture and relate them to events observed in vivo and discussed in
      accompanying reviews in this volume.

PMID- 15557800
TI  - Centrosome amplification and the origin of chromosomal instability in breast
      cancer.
AB  - The development and progression of aggressive breast cancer is characterized by
      genomic instability leading to multiple genetic defects, phenotypic diversity,
      chemoresistance, and poor outcome. Centrosome abnormalities have been implicated
      in the origin of chromosomal instability through the development of multipolar
      mitotic spindles. Breast tumor centrosomes display characteristic structural
      abnormalities, termed centrosome amplification , including: increase in
      centrosome number and volume, accumulation of excess pericentriolar material,
      supernumerary centrioles, and inappropriate phosphorylation of centrosome
      proteins. In addition, breast tumor centrosomes also show functional
      abnormalities characterized by inappropriate centrosome duplication during the
      cell cycle and nucleation of unusually large microtubule arrays. These
      observations have important implications for understanding the mechanisms
      underlying genomic instability and loss of cell polarity in cancer. This review
      focuses on the coordination of the centrosome, DNA, and cell cycles in normal
      cells and their deregulation resulting in centrosome amplification and
      chromosomal instability in the development and progression of breast cancer.

PMID- 15557801
TI  - Telomere shortening occurs early during breast tumorigenesis: a cause of
      chromosome destabilization underlying malignant transformation?
AB  - Chromosomal instability appears early during breast carcinogenesis and is
      considered a major driving force in malignant transformation. While current
      evidence suggests that centrosomal and mitotic checkpoint defects may, in large
      part, account for numerical chromosomal abnormalities, the mechanisms underlying
      structural chromosomal abnormalities remain largely unknown. Telomeres stabilize
      and protect chromosomal termini, but shorten due to cell division and oxidative
      damage. Moderate telomere shortening signals a tumor suppressive growth arrest in
      normal cells. Critically short telomeres, in the setting of abrogated DNA damage
      checkpoints, cause chromosomal instability due to end-to-end chromosomal fusions,
      subsequent breakage, and rearrangement, resulting in an increased cancer
      incidence in animal models. Recent results from high resolution in situ telomere
      length assessment in human breast tissues indicate that significant telomere
      shortening is prevalent in preinvasive breast lesions (DCIS), as well as focal
      areas of histologically normal epithelium from which breast carcinoma is thought
      to arise. Telomere shortening is therefore a strong candidate for the cause of
      structural chromosome defects that contribute to breast cancer development.

PMID- 15557802
TI  - Using chemical exchange to assign non-covalent protein complexes in slow exchange
      with the free state: enhanced resolution and efficient signal editing.
AB  - The formation of a ligand-protein complex oftentimes results in significant
      chemical shift changes. These changes may occur not only in the binding pocket
      but also in distal regions of the protein target. Therefore the reassignment of
      the backbone resonances in the complex is frequently a time consuming challenge.
      Here we present a suite of resolution-enhanced N(z)-exchange NMR experiments
      useful for rapidly assigning backbone (1)H and (15)N amide resonances of the
      ligand-bound form of a protein in slow exchange with its free state.
      Incorporation of semi-constant time frequency labeling periods into 3D N(z)
      exchange experiments in combination with the collection of resolution-enhanced 2D
      N(z)-exchange difference spectra leads to a powerful set of tools for analyzing
      protein-ligand complexes. This allows for both the assignment of the bound state
      and the rapid assessment of the protein binding interface. The proposed
      methodology is demonstrated on the complex formed by the dimerization-docking
      domain of the c-AMP-dependent protein kinase and the tethering domain of the dual
      binding A-kinase anchoring protein (AKAP).

PMID- 15557803
TI  - NMR structure of a complex between MDM2 and a small molecule inhibitor.
AB  - MDM2 is a regulator of cell growth processes that acts by binding to the tumor
      suppressor protein p53 and ultimately restraining its activity. While
      inactivation of p53 by mutation is commonly observed in human cancers, a
      substantial percentage of tumors express wild type p53. In many of these cases,
      MDM2 is overexpressed, and it is believed that suppression of MDM2 activity could
      yield therapeutic benefits. Therefore, we have been focusing on the p53-MDM2
      interaction as the basis of a drug discovery program and have been able to
      develop a series of small molecule inhibitors. We herein report a high resolution
      NMR structure of a complex between the p53-binding domain of MDM2 and one of
      these inhibitors. The form of MDM2 utilized was an engineered hybrid between the
      human and Xenopus sequences, which provided a favorable combination of relevancy
      and stability. The inhibitor is found to bind in the same site as does a highly
      potent peptide fragment of p53. The inhibitor is able to successfully mimic the
      peptide by duplicating interactions in three subpockets normally made by amino
      acid sidechains, and by utilizing a scaffold that presents substituents with
      rigidity and spatial orientation comparable to that provided by the alpha helical
      backbone of the peptide. The structure also suggests opportunities for modifying
      the inhibitor to increase its potency.

PMID- 15557804
TI  - Optimization of 13C direct detection NMR methods.
AB  - (13)C-detected experiments are still limited by their inherently lower
      sensitivity, as compared to the equivalent (1)H-detected experiments. Improving
      the sensitivity of (13)C detection methods remains a significant area of NMR
      research that may provide better means for studying large macromolecular systems
      by NMR. In this communication, we show that (13)C-detected experiments are less
      sensitive to the salt concentration of the sample solution than (1)H-detected
      experiments. In addition, acquisition can be started with anti-phase coherence,
      resulting in higher sensitivity due to the elimination of the final INEPT
      transfer step.

PMID- 15557805
TI  - 1H, 13C and 15N resonance assignments of poplar phloem glutaredoxin.

PMID- 15557806
TI  - 1H, 13C and 15N resonance assignments of the C-terminal BRCT domain from human
      BRCA1.

PMID- 15557807
TI  - 1H, 13C and 15N resonance assignment of the methionine sulfoxide reductase B from
      Neisseria meningitidis.

PMID- 15557808
TI  - Sequence-specific assignment and secondary structure determination of the 195
      residue complex formed by the Mycobacterium tuberculosis proteins CFP-10 and ESAT
      6.

PMID- 15557809
TI  - 1H, 15N and 13C resonance assignments of complement control protein module pair 2
      3 from the C4b-binding site of complement receptor type 1.

PMID- 15557810
TI  - 1H, 13C and 15N resonance assignment of the reduced form of thioredoxin h1 from
      Poplar, a CPPC active site variant.

PMID- 15557811
TI  - Early effect of Mycobacterium tuberculosis infection on Mac-1 and ICAM-1
      expression on mouse peritoneal macrophages.
AB  - Effect of M. tuberculosis infection was studied on the expression of
      intercellular adhesion molocule-1 (ICAM-1) and Mac-1 markers on murine peritoneal
      macrophages. Intraperitoneal administration of M. tuberculosis resulted in a
      marked increase in the proportion of Mac-1(+) cells whereas the proportion of
      ICAM-1(+) cells declined sharply 4 h post infection. Absolute numbers of Mac-1(+)
      and ICAM-1(+) cells however increased at all time points after the infection.
      Comparison of kinetics of changes observed in Mac-1(+) and ICAM-1(+) cell
      populations with differential leukocyte counts in peritoneal cells indicated that
      these alterations could be due to cellular influx, especially that of
      neutrophils, or up regulation of these markers on macrophages and other
      peritoneal cells. In adherent peritoneal macrophages infected in vitro with M.
      tuberculosis, proportion of Mac-1(+) and ICAM-1(+) cells increased markedly
      within 24 h of infection. Mean expression of these markers on per cell basis also
      increased significantly. Similar results were obtained by using RAW 264.7 mouse
      macrophage cell line, suggesting that the enhanced expression of Mac-1 and ICAM-1
      markers was a direct effect of M. tuberculosis infection and not mediated by
      contaminating cell types present in adherent macrophage preparations. Mac-1 and
      ICAM-1 expression was further studied on macrophages that had actually engulfed
      M. tuberculosis and compared with bystander macrophages without intracellular M.
      tuberculosis. For this purpose M. tuberculosis pre-stained with DilC18
      fluorescent dye were used for infecting adherent peritoneal macrophages. Mac-1
      and ICAM-1 expression on gated DilC18 positive and negative cell populations was
      analyzed. Our results indicate that the expression of Mac-1 and ICAM- 1 markers
      was significantly enhanced on all macrophages incubated with M. tuberculosis but
      was more pronounced on macrophages with internalized mycobacteria. Taken
      together, our results suggest that the expression of Mac-1 and ICAM-1 markers is
      significantly up regulated as a result of exposure and infection with M.
      tuberculosis. Since these markers play important role in the uptake of
      mycobacteria as well as in the process of antigen presentation by macrophages,
      their upregulation may be beneficial for generation of a protective immune
      response to M. tuberculosis.

PMID- 15557812
TI  - Evaluation of biological monitoring markers using genomic and proteomic analysis
      for automobile emission inspectors and waste incinerating workers exposed to
      polycyclic aromatic hydrocarbons or 2,3,7,8,-tetracholrodedibenzo-p-dioxins.
AB  - In this study, we investigated the effects of PAHs and dioxin on mRNA and plasma
      protein expression using genomic and proteomic analysis for automobile emission
      inspectors and waste incineration workers. About 54 workers from automobile
      emission inspection offices, 31 workers from waste incinerating company and 84
      unexposed healthy subjects were enrolled in this study. Urine and air samples
      were collected and analyzed by HPLC and GC/MS. Comet assays were carried out to
      evaluate any DNA damage in mononuclear and polynuclear cells. A significant
      difference in Olive tail moments in mononuclear cells was observed between
      exposed and control subjects (P < 0.0001). To examine the differences of the gene
      expression profile in automobile emission inspectors and waste incineration
      workers, radioactive complementary DNA microarrays were used to evaluate changes
      in the expression of 1,152 total genes. The gene expression profiles showed that
      11 genes were up-regulated and 4 genes were down-regulated in waste incinerating
      workers as compared with controls. Plasma proteins were analyzed by 2-dimentional
      electrophoresis with pH 3-10 NL IPG Dry strip. The protein expression profiles
      showed that 8 proteins were up- regulated and 1 protein, haptoglobin, was down-
      regulated in automobile emission inspectors and waste incineration workers. Serum
      paraoxonase/ arylesterase was found only in the plasma of waste incineration
      workers. The expression of genes and proteins involved in oxidative stress were
      up-regulated in both automobile emission inspectors and waste incineration
      workers. Several proteins, such as transthyrethin, sarcolectin and haptoglobin,
      that were highly up- or down-regulated, could serve as biological monitoring
      markers for future study.

PMID- 15557813
TI  - Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine
      treatment in lung cancer cells.
AB  - Ceramide generated from sphingomyelin in response to ionizing radiation has been
      implicated as a second messenger to induce cellular proapoptotic signals. Both
      ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS),
      might lead to sustained ceramide accumulation in cells more efficiently, thereby
      sensitizing them to gamma-radiation-induced cell death. To delineate this
      problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was
      evaluated following exposure to radiation together with or without C2-ceramide,
      DMS, or both. The treatment of ceramide/DMS synergistically decreased the
      survival of the irradiated cells compared with treatment with ceramide or DMS
      alone. Ceramide/DMS-treated cells displayed several apoptotic features after
      gamma-irradiation, including increased sub G(1) population, TUNEL-positive
      fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed
      ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and
      activation of caspase- 9 and -3 in a radiation-dose-dependent manner.
      Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the
      protein expression level of Bax, but also decreased Bcl-2 after gamma
      irradiation. Taken together, the present study indicates that the
      radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the
      dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.

PMID- 15557814
TI  - Sphingosine mediates FTY720-induced apoptosis in LLC-PK1 cells.
AB  - FTY720, a synthetic sphingoid base analog, was examined as a new sphingosine
      kinase inhibitor, which converts endogenous sphingosine into its phosphate form.
      With 20 microM of FTY720, sphingosine accumulated in the LLC-PK(1) cells in a
      time- and dose-dependent manner. The FTY720 treated cells showed a high
      concentration of fragmented DNA, a high caspase-3 like activity and TUNEL
      staining cells. It was also found that the sphingosine and sphinganine level
      increased in a time- and dose-dependent manner within 12 h after the FTY720
      treatment. The sphingosine kinase activity was reduced by FTY720 as much as other
      sphingosine kinase inhibitors, N, N-dimethylsphingosine (DMS), dl-threo
      dihydrosphingosine (DHS). The fragmented DNA content as a result of the 20 microM
      of FTY720 treatment and by 5 microM of the exogenously added BSA-sphingosine
      complex indicated typical apoptosis. Under similar conditions, the accumulated
      sphingosine concentration in all the cells was almost identical even though the
      sphingosine distribution inside the cells was somewhat different. These results
      indicate that the FTY720 induced apoptosis is associated with the inhibition of
      the sphingosine kinase activity and is strongly associated with the successive
      accumulation of sphingosine.

PMID- 15557815
TI  - Activated natural killer cell-mediated immunity is required for the inhibition of
      tumor metastasis by dendritic cell vaccination.
AB  - Immunization with dendritic cells (DCs) pulsed with tumor antigen can activate
      tumor-specific cytotoxic T lymphocytes (CTL), which is responsible for tumor
      protection and regression. In this study, we examined whether DCs pulsed with
      necrotic tumor lysates can efficiently prevent malignant melanoma tumor cell
      metastasis to the lung. DCs derived from mouse bone marrow were found to produce
      remarkably elevated levels of IL-12 after being pulsed with the tumor lysates.
      Moreover, immunization with these DCs induced CTL activation and protected mice
      from metastasis development by intravenously inoculated tumor cells. In addition,
      these DCs activated NK cells in vitro in a contact-dependent manner, and induced
      NK activities in vivo. Furthermore, NK cell depletion before DC vaccination
      significantly reduced the tumor-specific CTL activity, IFN-gamma production, and
      IFN-gamma- inducible gene expression, and eventually interfered with the
      antitumor effect of tumor-pulsed DCs. Finally, similar findings with respect to
      NK cell dependency were obtained in the C57BL/ 6J-bg/bg mice, which have severe
      deficiency in cytolytic activity of NK cells. These data suggest that the
      antitumor effect elicited by DC vaccination, at least in a B16 melanoma model,
      requires the participation of both cytolytic NK and CD8(+) T cells. The findings
      of this study would provide important data for the effective design of DC
      vaccines for cancer immunotherapy.

PMID- 15557816
TI  - Involvement of Sox-4 in the cytochrome c-dependent AIF-independent apoptotic
      pathway in HeLa cells induced by Delta12-prostaglandin J2.
AB  - Delta(12)-Prostaglandin (PG) J(2) is known to elicit an anti-neoplastic effects
      via apoptosis induction. Previous study showed Delta(12)-PGJ(2)-induced apoptosis
      utilized caspase cascade through cytochrome c-dependent pathways in HeLa cells.
      In this study, the cellular mechanism of Delta(12)-PGJ(2)- induced apoptosis in
      HeLa cells, specifically, the role of two mitochondrial factors; bcl-2 and
      apoptosis-inducing factor (AIF) was investigated. Bcl-2 attenuated Delta(12)
      PGJ(2)-induced caspase activation, loss of mitochondrial transmembrane potential
      (Deltapsi(m)), nuclear fragmentation, DNA laddering, and growth curve inhibition
      for approximately 24 h, but not for longer time. AIF was not released from
      mitochondria, even if the Deltapsi(m) was dissipated. One of the earliest events
      observed in Delta(12)-PGJ(2)-induced apoptotic events was dissipation of
      Deltapsi(m), the process known to be inhibited by bcl-2. Pre-treatment of z-VAD-
      fmk, the pan-caspase inhibitor, resulted in the attenuation of ym depolarization
      in Delta(12)-PGJ(2)-induced apoptosis. Up-regulation of Sox-4 protein by
      Delta(12)-PGJ(2) was observed in HeLa and bcl-2 overexpressing HeLa B4 cell
      lines. Bcl-2 overexpression did not attenuate the expression of Sox-4 and its
      expression coincided with other apoptotic events. These results suggest that
      Delta(12)-PGJ(2) induced Sox-4 expression may activate another upstream caspases
      excluding the caspase 9-caspase 3 cascade of mitochondrial pathway. These and
      previous findings together suggest that Delta(12)-PGJ(2)-induced apoptosis in
      HeLa cells is caspase-dependent, AIF-independent events which may be affected by
      Sox-4 protein expression up-regulated by Delta(12)-PGJ(2).

PMID- 15557817
TI  - Phospholipase D activity is elevated in hepatitis C virus core protein
      transformed NIH3T3 mouse fibroblast cells.
AB  - Hepatitis C Virus (HCV) is associated with a severe liver disease and increased
      frequency in the development of hepatocellular carcinoma. Overexpression of HCV
      core protein is known to transform fibroblast cells. Phospholipase D (PLD)
      activity is commonly elevated in response to mitogenic signals, and has also been
      overexpressed and hyperactivated in some human cancer cells. The aim of this
      study was to understand how PLD was regulated in the HCV core protein-transformed
      NIH3T3 mouse fibroblast cells. We observed that PLD activity was elevated in the
      NIH3T3 cells overexpressing HCV core protein over the vector alone-transfected
      control cells, however, expression levels of PLD protein and protein kinase C
      (PKC) in the HCV core protein-transformed cells was similar to the control cells.
      Phorbol 12-myristate 13-acetate (PMA), which is known to activate PKC, stimulated
      PLD activity significantly more in the core protein-transformed cells, in
      comparison with that of the control cells. PLD activity assay using PKC isozyme
      specific inhibitor and PKC translocation experiment showed that PKC-delta was
      mainly involved in the PMA- induced PLD activation in the core-transformed cells.
      Moreover, in cells overexpressing HCV core protein, PMA also stimulated p38
      kinase more potently than that of the control cells, and an inhibitor of p38
      kinase abolished PMA-induced PLD activation in cells overexpressing HCV core
      protein. Taken together, these results suggest that PLD might be implicated in
      core protein-induced transformation.

PMID- 15557818
TI  - Protein kinase A mediates microglial activation induced by plasminogen and
      gangliosides.
AB  - In the injured brain, microglia is known to be activated and produce
      proinflammatory mediators such as interleukin-1beta (IL-1beta), tumor necrosis
      factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). We
      investigated the role of protein kinase A (PKA) in microglial activation by both
      plasminogen and gangliosides in rat primary microglia and in the BV2 immortalized
      murine microglial cell line. Both plasminogen and gangliosides induced IL-1beta,
      TNF-alpha and iNOS mRNA expression, and that this expression was inhibited by the
      addition of the PKA inhibitors, KT5720 and H89. Both plasminogen and gangliosides
      activated PKA and increased the DNA binding activity of the cAMP response element
      binding protein (CREB). Furthermore, KT5720 and H89 reduced the DNA binding
      activities of CREB and NF-kappaB in plasminogen-treated cells. These results
      suggest that PKA plays an important role in plasminogen and gangliosides- induced
      microglial activation.

PMID- 15557819
TI  - Transcriptional regulation of Zic3 by heterodimeric AP-1(c-Jun/c-Fos) during
      Xenopus development.
AB  - The heterodimeric c-Jun/c-Fos, an activator protein-1 (AP-1) has been implicated
      in mesoderm induction (Dong et al., 1996; Kim et al., 1998) whereas the homodimer
      of c-Jun was reported to be involved in neural inhibition during the early
      development of Xenopus embryos. During the early vertebrate development AP-1
      involvement in the neural induction is still not clearly understood. We report
      here that AP-1 has a role in Zic3 expression, a critical proneural gene and a
      primary regulator of neural and neural crest development (Nakata et al., 1997;
      Nakata et al., 1998). AP-1 was able to induce the Zic3 gene in a dose dependent
      manner but other homo- or hetero-dimeric proteins, such as c-Jun/c-Jun, JunD/FosB
      or JunD/Fra-1 were not. The inhibition of AP-1 activity using morpholino
      antisenses of c-jun mRNAs blocked the Zic3 expression induced by activin. In
      addition, co-injection of c-jun mRNA rescued the down-regulated Zic3 expression.
      The promoter region of isolated Zic3 genomic DNA was found to possess several
      consensus-binding site of AP-1. Thus, in the functional assays, AP-1 could
      increase promoter activity of Zic3 gene. These findings suggest that proneural
      gene, Zic3 may be regulated by heterodimeric AP-1(c-Jun/c-Fos) and it may have a
      role in activin signaling for the regulation of neural specific gene, Zic3.

PMID- 15557820
TI  - Extracellular ATP is generated by ATP synthase complex in adipocyte lipid rafts.
AB  - Mitochondrial biogenesis is known to accompany adipogenesis to complement ATP and
      acetyl-CoA required for lipogenesis. Here, we demonstrated that mitochondrial
      proteins such as ATP synthase alpha and beta, and cytochrome c were highly
      expressed during the 3T3-L1 differentiation into adipocytes. Fully-differentiated
      adipocytes showed a significant increase of mitochondria under electron
      microscopy. Analysis by immunofluorescence, cellular fractionation, and surface
      biotinylation demonstrated the elevated levels of ATP synthase complex found not
      only in the mitochondria but also on the cell surface (particularly lipid rafts)
      of adipocytes. High rate of ATP (more than 30 microM) synthesis from the added
      ADP and P(i) in the adipocyte media suggests the involvement of the surface ATP
      synthase complex for the extracellular ATP synthesis. In addition, this ATP
      synthesis was significantly inhibited in the presence of oligomycin, an ATP
      synthase inhibitor, and carbonyl cyanide m-chlorophenylhydrazone (CCCP), an ATP
      synthase uncoupler. Decrease of extracellular ATP synthesis in acidic but not in
      basic media further indicates that the surface ATP synthase may also be regulated
      by proton gradient through the plasma membrane.

PMID- 15557821
TI  - Der f 2 activates phospholipase D in human T lymphocytes from Dermatophagoides
      farinae specific allergic individuals: involvement of protein kinase C-alpha.
AB  - The major house-dust mite allergen, Der f 2, stimulates the phospholipase D (PLD)
      in T lymphocytes from Dermatophagoides farinae specific allergic individuals. PLD
      activity increased more than two-fold in T cells from allergic patients compared
      with those cells from normal controls with maximal responses within 30 min after
      exposure of Der f 2. A well-known PLD activator PKC-alpha was found to be
      translocated to membrane from cytosol in Der f 2-treated T cells from
      Dermatophagoides farinae specific allergic individuals. Down-regulation of PKC
      alpha with phorbol myristate acetate pretreatment for 24 h abolished Der f 2
      induced PLD activation. Ro 320432, PKC inhibitor also reduced the effects of Der
      f 2-induced PLD activation suggesting that PKC-alpha acts as upstream activator
      of PLD in Der f 2-treated T cells. Taken together, the present data suggest that
      Der f 2 can stimulate PLD activity through the PKC-alpha activation in T cells
      from Dermatophagoides farinae allergic individuals.

PMID- 15557822
TI  - Involvement of mitogen-activated protein kinases and p21Waf1 in hydroxyurea
      induced G1 arrest and senescence of McA-RH7777 rat hepatoma cell line.
AB  - Hydroxyurea is commonly used to treat hematologic disorders and some type of
      solid tumors, but the mechanism for its therapeutic effect is not clearly known.
      In this study, we examined the effect of hydroxyurea on rat hepatoma McA-RH7777
      cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal
      transduction pathways and p21(Waf1), p27(Kip1) and p53. Rat hepatoma McA-RH7777
      cells treated with hydroxyurea for 7 days, caused the inhibition of cell growth
      in a dose-dependent manner. But, this growth inhibition was not caused by
      necrosis or apoptosis but instead was associated with cell senescence-like change
      as evidenced by senescence associated-beta-galactosidase staining, and cells
      arrest at G1 phase of cell cycle. Phosphorylation of MAP kinases, such as ERK,
      JNK, and p38, was found to be decreased after treatment of cells with
      hydroxyurea. But, the expression of p21(Waf1) was increased, while p27(Kip1) and
      p53 were not detected in hydroxyurea treated rat hepatoma cells. Hydroxyurea
      treatment induced G1 arrest and a senescence-like changes in rat hepatoma McA
      RH7777 cells may be the likely results of signal disruption of MAP kinases (ERK,
      JNK, and p38 MAP kinase) and p21(Waf1) over-expression.

PMID- 15557823
TI  - Age-related decline in expression of calnexin.
AB  - Aging is accompanied by the changes in the cells that decrease their capacity to
      respond to various forms of stress. Cells are known to respond to stresses
      through expression of stress-response proteins, heat-shock proteins composed of
      molecular chaperones. Recent studies suggest that chaperone level and stress
      induced chaperone expression could decrease with aging. The aim of the present
      study is to identify chaperones that show a significant change in protein
      expression with aging. We used an in vitro aging model system of human diploid
      fibroblasts (HDF). Proteome analysis of HDF showed that endoplasmic reticulum
      (ER) chaperone, calnexin, significantly decreased with aging. Oxidative stress
      induced expression of calnexin also attenuated in old HDF compared to young
      cells. These findings suggest calnexin decreases with aging and might contribute
      to a cytoprotection in a variety of human age-related diseases.

PMID- 15557828
TI  - Effect of preoperative dexamethasone on edema of oral and extra-oral structures
      following trans-oral decompression and posterior fusion.
AB  - We investigated the anti-edema effect of intravenous dexamethasone in a
      randomized, double-blinded, placebo-controlled study in 40 ASA physical status I
      and II patients scheduled for trans-oral decompression and posterior fusion.
      Patients were divided into two groups to receive either placebo or 10 mg
      dexamethasone one hour prior to induction of anesthesia. After anesthesia
      induction, oral structures were graded as swelling grade 0 at direct
      laryngoscopy. Duration of trans-oral surgery, duration of posterior fusion, and
      total duration of surgery were recorded. After completion of surgery, direct
      laryngoscopy was repeated, and swelling was graded from 1 to 4. Patients who had
      a swelling grade of 1 or 2 were extubated while grades of 3 and 4 were
      transferred to a neurosurgical intensive care unit, and re-assessments were
      performed 12 hours apart. Patients with swelling grades of 1 and 2 were extubated
      on each assessment. On statistical analysis of the results, the study found that
      in comparison to placebo, patients in the dexamethasone group were extubated
      earlier (P < 0.006, Chi Square for trend). Total duration of surgery and duration
      of posterior fusion were significantly greater (P < 0.05) in patients who had
      swelling grade >2 than in patients who had swelling grade < or =2 at completion
      of surgery (192.50 +/- 16.26, 356.07 +/- 17.06 minutes versus. 158.27 +/- 9.07,
      311.41 +/- 14.06 minutes).

PMID- 15557829
TI  - ECG artifacts during intraoperative high-field MRI scanning.
AB  - High-field magnetic resonance imaging (MRI) (1.5 T) has recently been introduced
      into the neurosurgical operating room for intraoperative resection control and
      functional neuronavigational guidance. However, long-lasting neurosurgical
      procedures in an operating room equipped with a high-field MRI scanner raise new
      challenges to the anesthesiologist. In particular, monitoring of vital signs
      during anesthesia requires equipment compatible with working in close vicinity to
      the strong magnetic field. However, even MRI-compatible electrocardiographic
      (ECG) monitoring interferes with electromagnetic fields, so several ECG artifacts
      can be observed in static and pulsed magnetic fields. As shown in this study,
      pulsed high-frequency fields induce characteristic field frequency-based
      artifacts in the ECG that can imitate malignant arrhythmia or provoke ST-segment
      abnormalities. The knowledge of possible and characteristic ECG artifacts during
      high-field MRI is therefore essential to prevent misinterpretation. Moreover,
      interference-free parameters such as pulse oximetry or invasive blood pressure
      curves are highly relevant during intraoperative MRI scans.

PMID- 15557830
TI  - Transesophageal echocardiography as a guide for patient positioning before
      neurosurgical procedures in semi-sitting position.
AB  - With an incidence of a patent foramen ovale in nearly one fourth of the normal
      population, neurosurgical procedures in the semi-sitting position are associated
      with the risk of paradoxical air embolism. The present study was undertaken to
      evaluate an anesthetic concept to detect a patent foramen ovale with the help of
      transesophageal echocardiography in anesthetized patients before neurosurgical
      procedures in the semi-sitting position. Transesophageal echocardiography was
      performed after induction of anesthesia before surgery to avoid additional
      physical and psychologic stress for the patients. Thirty-five neurosurgical
      patients scheduled for elective surgery in the semi-sitting position were
      examined with help of contrast transesophageal echocardiography. The data of the
      examined patients were analyzed with respect to efficiency, logistic efforts, and
      adverse events. Contrast transesophageal echocardiography was combined with a
      ventilation maneuver to increase right atrial pressure. A patent foramen ovale
      was detected in 3 of 35 patients. These patients were operated on in a supine
      position. Oral insertion of the echoprobe was possible in all patients without
      difficulties. A short-lasting hypertension was observed in 5 patients despite
      adequate analgesia and sedation. The average time of examination was 25 minutes.
      None of the patients showed paradoxical air embolism as judged by postoperative
      neurologic assessment. Contrast transesophageal echocardiography combined with a
      ventilation maneuver is an effective method in detecting a patent foramen ovale.
      Moreover, transesophageal echocardiography is a clinical guide to patient
      positioning. The method of anesthetic management presented to examine
      anesthetized patients immediately before surgery means less physical and
      psychologic stress for the patients and causes approximately a 30-minute delay of
      surgery.

PMID- 15557831
TI  - Increased incidence of emergency airway management after combined anterior
      posterior cervical spine surgery.
AB  - Among some kinds of cervical spine surgeries, combined anterior-posterior
      cervical spine surgery (CAP-CS surgery) requires prolonged operative time and
      highly invasive procedure. This study was performed to determine whether CAP-CS
      surgery was associated with increased risk of emergency airway management
      compared with other cervical spine surgeries (O-CS surgeries). The records of the
      patients who underwent cervical spine surgery between July 2001 and March 2003 at
      our institution were reviewed retrospectively, and we determined whether the CAP
      CS surgery was associated with an increased risk of emergency airway management
      in comparison with O-CS surgeries, using the logistic regression analysis. A
      total of 165 were eligible for inclusion in the study. A total of 127, 20, 11, 5,
      and 2 patients suffered from cervical myelopathy, traumatic cervical spinal cord
      injury, atlantoaxial dislocation, cervical spinal tumors, and cervical pyogenic
      spondylitis, respectively. The operative approaches were CAP-CS surgery, anterior
      surgery, posterior surgery, and atlantoaxial surgery in 10, 56, 88, and 11
      patients, respectively. Thus, the operative approaches were CAP-CS surgery in 10
      patients and O-CS surgeries in 155 patients. Postoperative emergency airway
      management was required in 7 of the 10 patients (70%) who underwent CAP-CS
      surgery, and 2 of the 155 patients (1%) who underwent O-CS surgeries. The
      increased risk of postoperative emergency airway management imposed by CAP-CS
      surgery was 178.5 by an odds ratio, with a 95% confidence interval of 25.6 to
      1246. The results show that CAP-CS surgery provides a major risk factor for
      postoperative emergency airway management.

PMID- 15557832
TI  - Changes in intraocular pressure in anesthetized prone patients.
AB  - BACKGROUND: Postoperative visual loss occurs more commonly in patients placed
      prone. The mechanism may be raised intraocular pressure (IOP) causing an ischemic
      oculopathy. METHODS: IOP was measured in 20 patients undergoing spinal surgery.
      The IOP was measured prior to intubation, immediately after pronation, and at the
      end of surgery before the patient was returned to the supine position. Duration
      of surgery, method of head stabilization and standard physiological parameters
      were recorded. RESULTS: Both measurements of median IOP in the prone position
      were significantly higher than that in the supine position (P < 0.001). There was
      no evidence of a relationship between rise in IOP and duration of surgery, age,
      or body mass index. There was weak evidence of a tendency for patients whose
      heads were on pillows to have higher values of IOP at the end of surgery than
      patients whose heads were supported in pins. CONCLUSION: IOP increases when
      anesthetized patients are placed in the prone position.

PMID- 15557833
TI  - Does famotidine induce thrombocytopenia in neurosurgical patients?
AB  - The incidence of thrombocytopenia in neurosurgical patients prescribed famotidine
      is unknown. Using hospital records of neurosurgery patients treated between July
      2001 and July 2002, a retrospective cohort study was performed comparing platelet
      counts in patients treated with famotidine with a similar group of patients who
      were not prescribed an H2 antagonist. Patients were excluded if: 1) platelets
      were less than 150,000 prior to famotidine administration; 2) pre-drug and post
      drug platelets were not drawn; 3) they were concurrently taking a potential
      thrombocytopenic inducing drug; or 4) disseminated intravascular coagulation,
      thrombocytopenic purpura, or any other confounding hematologic disorder
      developed. Seventeen of 50 (34%) patients on famotidine developed
      thrombocytopenia compared with 11 of 98 (11.2%) of those untreated (P = 0.002).
      In this retrospective study, neurosurgical patients on famotidine developed
      thrombocytopenia statistically significantly more often than those untreated.
      Although no clinically significant sequelae developed as a result of the
      thrombocytopenia, if these findings are confirmed by a prospective study, proton
      pump inhibitors and sucralfate, with their similar efficacy, may be a better
      choice for gastrointestinal prophylaxis in neurosurgical patients.

PMID- 15557834
TI  - Headache in guillain-barre syndrome.
AB  - Severe headache in Guillain-Barre syndrome is rare. We report the management of a
      young patient with Guillain-Barre syndrome who suffered severe headache, which
      was not relieved by conventional analgesics. There was evidence of raised
      intracranial pressure. Insertion of lumbar drain and drainage of cerebrospinal
      fluid relieved her headache.

PMID- 15557835
TI  - Monitoring intravascular volumes to direct hypertensive, hypervolemic therapy in
      a patient with vasospasm.
AB  - The common therapeutic approach to patients, who develop vasospasm following
      subarachnoid hemorrhage, is usually composed of hypertension, hypervolemia, and
      hemodilution (HHH). This therapy often leads to cardiopulmonary complications,
      including significant heart failure and pulmonary edema. We describe a 40-year
      old woman who developed vasospasm 8 days after surgery for clipping an aneurysm,
      following a large subarachnoid hemorrhage. The patient required HHH therapy with
      a very high blood pressure to optimize her clinical neurologic status, but she
      started to develop pulmonary edema resulting from this therapy. This manifested
      as a need for increasing oxygen to maintain a normal arterial saturation. To
      avoid further hemodynamic compromise, we used a new monitor of cardiac function
      to measure intravascular volumes and quantify pulmonary edema to help titrate the
      fluid management of a patient in severe vasospasm. We conclude that monitoring
      volumes with the PiCCO cardiac monitor can help make clinical decisions in
      patients requiring HHH. This enables maintaining a hypertensive and hypervolemic
      state while avoiding cardiopulmonary complications such as heart failure and
      pulmonary edema. It may also help prevent the need for mechanical ventilation in
      these situations.

PMID- 15557836
TI  - Transient cardiac asystole in transsphenoidal pituitary surgery: a case report.
AB  - Unlike other cardiac arrhythmia, asystole during neurosurgical procedures is not
      reported in the literature. We describe such a case during transsphenoidal
      pituitary surgery in a patient who was not having any history of associated
      cardiac problems. Its possible cause in relation to the perioperative sequence of
      events has been discussed.

PMID- 15557838
TI  - Anesthetics provide limited but real protection against acute brain injury.

PMID- 15557839
TI  - Anesthetic mediated neuroprotection: established fact or passing fancy?

PMID- 15557842
TI  - Dexmedetomidine as primary sedative in CEA patients.

PMID- 15557843
TI  - Venous air embolism in an awake patient undergoing placement of deep brain
      stimulators.

PMID- 15557844
TI  - Reversible unilateral blindness after lumbar spine surgery: a role for
      cerebrospinal fluid leakage?

PMID- 15557846
TI  - Educating the profession: fifty years of postgraduate education.

PMID- 15557845
TI  - Does general anesthesia potentiate the GABA-ergic action of intrathecal baclofen?

PMID- 15557849
TI  - Refractive astigmatism and the toricity of ocular components in human infants.
AB  - PURPOSE: Many studies have characterized astigmatism in infancy, but few have
      been longitudinal or contained ocular component data. This study characterized
      the frequency, orientation, and longitudinal change with age of infant
      astigmatism. Additional factors investigated were the influence of early
      astigmatism on emmetropization and its relation to corneal and lenticular
      toricity. METHODS: Three hundred two infants were enrolled in the study. Of
      these, 298 provided data for at least one visit at 3 +/- 1 months, 9 +/- 1
      months, 18 +/- 2 months, and 36 +/- 3 months. Testing included cycloplegic
      retinoscopy (cyclopentolate 1%), video-based keratophakometry, and
      ultrasonography over the closed eyelid. RESULTS: Astigmatism > or =1.00 DC was
      common at 3 months of age (41.6%) but decreased in prevalence to 4.1% by 36
      months (p < 0.0001). The most common orientation was with-the-rule at 3 months
      (37.0% compared with 2.7% for against-the-rule) but against-the-rule at 36 months
      (3.2% compared with 0.9% for with-the-rule). Most of the change in the average
      value of the horizontal/vertical component of astigmatism (J0) occurred between 3
      and 9 months (-0.26 +/- 0.36 D; p < 0.0001) with no significant change between 9
      and 36 months (-0.05 +/- 0.36 D; p=0.09). Spherical equivalent refractive error
      was not correlated with J0 at 3 and 9 months (R=0.002, p=0.48 and R=0.001,
      p=0.56, respectively). The two were only weakly correlated at 18 and 36 months
      (R=0.06 for each age, p <0.0001, p=0.0002, respectively). Changes in spherical
      equivalent between 3 and 9 months were unrelated to either the initial value of
      J0 (partial R for J0=0.0001; p=0.85) or the change in J0 (partial R for change in
      J0=0.0031; p=0.31). Across all the ages, corneal toricity was with-the-rule, and
      lenticular toricity was against-the-rule (produced by the toricity of the
      posterior lens surface). The cornea and anterior lens surface became more
      spherical with age, contributing to the shift away from with-the-rule refractive
      astigmatism. Toricity of all the refractive surfaces became less variable with
      age. CONCLUSIONS: Consistent with many reports, astigmatism was common in early
      infancy but decreased in prevalence with age, particularly when with-the-rule in
      orientation. The reduction in percentage of infants with astigmatism appeared to
      be caused by decreases in the toricity of the cornea and the anterior lens
      combined with decreases in the variability of corneal and lenticular surfaces.
      Astigmatism in infancy appeared to be unrelated to emmetropization of spherical
      equivalent refractive error.

PMID- 15557850
TI  - Oculometric characteristics of extreme hypermetropia in two faroese families.
AB  - PURPOSE: To describe and analyze the oculometric features of small eyes with high
      hypermetropia in two Faroese families, with emphasis on refractive components.
      METHODS: Members of the two families (N=40; age, 1 to 77 years), including 15
      cases of extreme hypermetropia (+7.5 to +19.25 D), had an ophthalmic evaluation
      including refractometry, keratometry, and axial ocular measurements using A-scan
      ultrasound. Eye-wall thickness was assessed using B-scan. Nonparametric
      statistics were used, mainly the Mann-Whitney U test. RESULTS: In the two
      families, there were six and nine probands, respectively, with hypermetropia more
      than +7 D and short eyes as defined by axial eye lengths <21 mm. The median
      corrected visual acuity was 0.4 (range, 0.2 to 0.9). Gross fundus abnormalities
      were not observed. All 15 had a short posterior segment with a thick eye wall and
      a relatively thick lens. Furthermore, steep and rather small corneas were
      present. In one of the families, 70% of the affected had a corneal curvature
      radius of < or =7.0 mm. Five probands from family 2 were labeled as possibly
      affected because of hypermetropia and borderline axial length findings (21 to 22
      mm). The remaining 20 subjects had visual acuity and oculometric findings within
      physiologic limits. CONCLUSIONS: The axial measurement features in our series of
      highly hypermetropic eyes mainly presented as an extension downward from the
      hypermetropic bottom line of the normal distribution. The axial shortness of the
      eyes was primarily the result of a short posterior eye segment ("posterior
      microphthalmos"). A steep cornea was a feature in most small eyes in our series,
      particularly in one family branch.

PMID- 15557851
TI  - The Quality of Life Impact of Refractive Correction (QIRC) Questionnaire:
      development and validation.
AB  - BACKGROUND: The purpose of the study was to develop a questionnaire that could
      quantify the quality of life (QOL) of people with refractive correction by
      spectacles, contact lenses, and refractive surgery in the prepresbyopic age
      group. METHODS: The questionnaire was developed and validated using traditional
      methods and Rasch analysis. A 90-item pilot questionnaire was developed through
      extensive literature search and use of professional and lay focus groups. Pilot
      study data were obtained from 306 subjects for item reduction to produce the 20
      item Quality of Life Impact of Refractive Correction (QIRC) questionnaire.
      Validity and reliability studies (test-retest reliability with intraclass
      correlation coefficient and Bland-Altman limits of agreement, and internal
      consistency with Rasch fit statistics, factor analysis, and Cronbach's alpha)
      were performed from data of an additional 312 subjects. RESULTS: Rasch analysis
      demonstrated QIRC has good precision, reliability, and internal consistency
      (person separation, 2.03; reliability, 0.80; root-mean-square measurement error,
      3.25; mean square +/- SD infit, 0.99 +/- 0.38; outfit, 1.00 +/- 0.39; item infit
      range, 0.70 to 1.24; and item outfit range, 0.78 to 1.32). The items (mean score,
      50.3 +/- 7.3) were well targeted to the subjects (mean score, 47.8 +/- 5.5) with
      a mean difference of 2.45 (scale range, 0 to 100) units. Test-retest reliability
      (intraclass correlation coefficient, 0.88; coefficient of repeatability, +/-6.85
      units), factor loading range (0.40 to 0.76), and Cronbach's alpha (0.78) also
      indicated the reliability and validity of QIRC. CONCLUSIONS: The 20-item QIRC
      questionnaire, which quantifies the QOL of people with refractive correction by
      spectacles, contact lenses, and refractive surgery in the prepresbyopic age
      group, was developed using Rasch analysis and shown to be valid and reliable. The
      use of Rasch scaling allows scores to be treated as a valid continuous variable.
      QIRC has broad applicability for cross-sectional and outcomes research.

PMID- 15557852
TI  - Optical section retinal imaging and wavefront sensing in diabetes.
AB  - PURPOSE: To investigate differences in higher-order ocular aberrations and in
      optical section retinal image resolution between healthy normal and diabetic
      subjects. METHODS: An optical imaging system was established for combined retinal
      optical section imaging and wavefront sensing. A laser beam was expanded and
      focused to a point on the retina by the optics of the eye. For optical section
      retinal imaging, a cylindrical lens was placed in the path of the incident laser
      beam to form a focused line on the retina. Because of the angle between the
      incident laser and imaging path, an optical section image of the retina was
      captured. For wavefront sensing, a Shack-Hartmann aberrometer was incorporated in
      the imaging system. Twenty-two subjects with diabetes (average age, 52 +/- 12
      years) and 13 normal subjects (average age, 47 +/- 9 years) were imaged. Retinal
      depth resolution was determined from the width of the laser line on the retina.
      Higher-order ocular aberrations were determined from the root mean square of the
      third to seventh Zernike terms, characterizing the wavefront aberration function.
      The data were analyzed statistically using Student's t-test and linear
      regression. RESULTS: Higher-order ocular aberrations in diabetic subjects were
      significantly higher than in normal subjects (p=0.03). The retinal image depth
      resolution in diabetic subjects was significantly lower than in normal subjects
      (p <0.001). The retinal image depth resolution was inversely correlated with
      higher-order aberrations (r=-0.5; p=0.007; N=35). CONCLUSIONS: The results
      demonstrate disease-related increases in higher-order ocular aberrations that
      influence retinal image resolution in diabetic eyes. This information is useful
      for designing high-resolution retinal imaging systems applicable for eyes with
      retinal disease.

PMID- 15557853
TI  - Spatial compression and adaptation with the low vision telescope.
AB  - PURPOSE: Geometrical analysis of monocular visual information specifying distance
      shows that a low vision telescope compresses optically specified distances by a
      factor about equal to its magnification. Using a group of eight visually healthy
      adults, we investigated the initial perceptual effect of putting on a 2x Galilean
      telescope and the adaptation produced by wearing the telescope. METHODS: Viewing
      was monocular, and the environment was only visible through the telescope.
      Because the telescope reduced the field of view to 13 degrees , we also tested a
      different group of eight visually normal adults who wore a simple monocular tube
      that restricted the field of view to 13 degrees . We measured perceived distance
      in a corridor using a visually directed open-loop walking task with distances
      ranging from 4 to 8 m. For both groups, monocular distance perception was
      measured before putting on the viewing device (baseline), immediately after
      putting on the viewing device (preadaptation), after wearing the viewing device
      during a 30-minute period of visual-motor activities (postadaptation), and
      immediately after taking off the viewing device (aftereffect). RESULTS: Comparing
      preadaptation with baseline measurements, the viewing devices produced a 15.4%
      initial compression of perceived distance on average. Comparing aftereffect with
      baseline measurements, the adaptation period produced a negative aftereffect that
      was 56.5% of the initial compression, thus showing substantial adaptation. The
      initial compression and the adaptation were highly significant effects, but
      neither effect was significantly different for the telescope group and the tube
      group. CONCLUSION: We conclude that free head movements in a structured
      environment can largely overcome the optically specified compression of distance
      produced by the 2x magnification of a low vision telescope, but there remains a
      significant initial compression of perceived distance that is produced by the
      restricted field of view. This compression can be substantially reduced by a
      short period of interaction with the environment.

PMID- 15557854
TI  - Repeatability and effects of sequential measurements with POBF tonograph.
AB  - AIMS: (1) To investigate the effect of performing sequential measurements using a
      Pulsatile Ocular Blood Flow (POBF) Tonograph on POBF and intraocular pressure
      (IOP) measurements; (2) to determine any effect on IOP caused by performing POBF
      measurements on the fellow eye; and (3) to assess repeatability of measurements
      obtained using the POBF Tonograph. METHODS: Forty-six normal adult subjects (13
      men, 33 women; age range, 18 to 55 years) took part in the present study. Twenty
      one subjects underwent sequential measurements with a POBF Tonograph on five
      different occasions with five different time intervals (1, 2, 5, 10, and 15
      minutes) between recordings. Twenty subjects underwent a baseline measurement on
      one eye with the POBF Tonograph, followed by repeat measurements in both eyes
      after 15 minutes. An additional 25 subjects underwent sequential measurements on
      the same eye with an interval of 15 minutes between readings. The intraclass
      correlation coefficient and Bland-Altman plots were used to assess repeatability
      of the instrument for all 46 subjects for the 15-minute time interval. RESULTS:
      In all the groups, repeated measurement resulted in a lower recorded IOP. A
      multivariate analysis of variance indicated that there was a significant decrease
      in IOP when measurements were repeated within 15 minutes (p=0.024), but there was
      no significant change in the POBF values (p=0.76). The recorded IOP was
      significantly lower when sequential measurements were performed with an interval
      of 1 minute (p <0.01) compared with longer time intervals. The decrease in IOP
      between baseline and the repeat measurement was significantly greater in the 1
      minute interval group compared with the 15-minute interval group (p <0.005).
      There was no significant difference in POBF values between the baseline and
      repeat measurements in any group. There was no significant change in IOP induced
      by a single measurement on the fellow eye (p >0.05). The intraclass correlation
      coefficient value indicated good agreement between the values of the baseline and
      repeat measurements using the POBF Tonograph but had wide upper and lower limits
      of agreement. CONCLUSION: If IOP measurements have to be repeated using the POBF
      Tonograph, they are best done after an interval of at least 2 minutes and
      preferably after 15 minutes. Use of the POBF Tonograph had no significant
      immediate effect on the IOP or POBF values obtained from a fellow eye.

PMID- 15557855
TI  - Tensions in the field: teaching standards of practice in optometry case
      presentations.
AB  - PURPOSE: Professional identity formation and its relationship to case
      presentations were studied in an optometry school's onsite clinic. METHODS: Eight
      optometry students and six faculty optometrists were audio-recorded during 31
      oral case presentations and the teaching exchanges related to them. Using
      convenience sampling, interviews were audio-recorded of four of the students and
      four of the optometrists from the field observations. After transcribing these
      audio-recordings, the research team members applied a grounded theory method to
      identify, test, and revise emergent themes. The theme reported herein pertains to
      communicating standards of practice. RESULTS: Faculty optometrists demonstrated
      three ways of communicating standards of practice to optometry students during
      case presentations: Official Way, Our Way, and My Way. Although there were
      differences between these standards, the rationale for the disparities was rarely
      explicitly articulated by the instructors to the students. Without this
      information, the incongruity among the standards was left to the students to
      interpret on their own. CONCLUSIONS: The risk created by faculty not articulating
      the rationale underlying standards of practice was that students misinterpreted
      the optometrists' ways as idiosyncratic. Thus, opportunities were missed in the
      educational setting to assist students in making responsible decisions, locating
      their position in practice, and shaping their professional identity. Competing
      responsibilities of patient care and student education left instructors with
      little time to articulate rationale for standards of practice. Therefore,
      educators must reflect on innovative ways to bring into relief the logic behind
      their actions when working with novices.

PMID- 15557856
TI  - Realizability of optical systems of given linear optical character.
AB  - The linear optical character of an optical system is represented by a particular
      type of 5 x 5 matrix. This article shows that the converse is also true, namely,
      that an optical system can be constructed in principle with linear optical
      character represented by any matrix of this type. In other words, every matrix of
      this type is realizable as an optical system. The system may have astigmatic and
      decentered elements.

PMID- 15557857
TI  - [Comparison of once-daily nonpreserved timolol and timolol maleate gel-forming
      solution associated with latanoprost].
AB  - AIM: To compare the efficacy and safety of a single daily instillation of
      nonpreserved timolol to a timolol maleate gel-forming solution in patients with
      chronic glaucoma or ocular hypertension already treated with latanoprost.
      PATIENTS AND METHODS: A randomized, prospective, multicenter, open, parallel
      group clinical trial was undertaken with 73 patients with chronic glaucoma
      treated with latanoprost and a timolol maleate gel-forming solution. In 36
      patients, the previous regimen was substituted by nonpreserved timolol given
      instead of timolol maleate gel for 3 months. The changes in intraocular pressure
      (IOP) were recorded as well as local and systemic tolerance and patient
      compliance. RESULTS: At 3 months, both regimens were found equivalent in
      maintaining IOP control between D0 and D84. The difference with baseline was 
      0.08 +/- 2.22 mmHg and -0.38 +/- 2.41 mmHg in the nonpreserved timolol group and
      in the timolol maleate gel-forming solution group, respectively (CI 95% [-0.79;
      1.38]). After 84 days of treatment, blurred vision (5.9%) and eyelid deposits
      (5.9%) were reduced in the preservative-free timolol group compared to the other
      group (respectively, 33.3% and 24.2%). These differences were statistically
      significant for both signs (blurred vision: p < 0.0001 and for eyelid deposits: p
      = 0.03). CONCLUSION: This short-term study has demonstrated the equivalence of
      nonpreserved timolol to timolol maleate gel-forming solution in terms of IOP
      control. Moreover, the local tolerance of nonpreserved timolol was better.

PMID- 15557858
TI  - [Advantages of the in vivo HRT2 corneal confocal microscope for investigation of
      the ocular surface epithelia].
AB  - PURPOSE: To show the advantages of the in vivo HRT2 confocal microscope corneal
      module for studying the superficial and peripheral corneal and conjunctival
      epithelia. MATERIAL AND METHODS: We examined 15 patients whose superficial cornea
      was healthy and ten patients with keratoconjunctivitis sicca and/or rosacea. Some
      conjunctival imprints where taken on patients with superficial ocular disease and
      examined by immunofluorescence. RESULTS: We found superficial corneal epithelial
      cells, corneoconjunctival Langerhans and dendritic cells, goblet cells, limbic
      epithelial junction, new blood vessels, as well as deeper corneal structures such
      as Bowman's membrane, keratocytes, corneal nerves, and endothelium. We also
      observed pathological corneal epithelium in keratoconjunctivitis sicca and
      substantial inflammatory and vascular changes in rosacea. In two cases of stem
      cell deficiency associated with rosacea, we observed goblet cells in the corneal
      epithelium. An interesting anatomical-clinical parallelism between in vivo
      confocal microscopy images and those obtained by ex vivo immunofluorescence was
      observed. DISCUSSION: Central corneal pictures after explorations by in vivo HRT2
      confocal microscopy are similar to those obtained with standard confocal
      microscopy. But conjunctiva, peripheral cornea and limbus are better examined at
      the surface and at medium depth with the HRT2. Diagnosis and therapy of
      superficial corneoconjunctival and limbal diseases are therefore made easier in
      vivo.

PMID- 15557859
TI  - [Ocular injuries and childbirth].
AB  - INTRODUCTION: Severe ocular traumatisms related to childbirth are rare and often
      subordinate to maneuvers with instruments. The aim of this study was to report on
      the different severe ocular injuries that might occur during childbirth and their
      possible consequences. There can be several of these ocular injuries. PATIENTS
      AND METHODS: Since 1984, we have examined 11 cases of this type of traumatism.
      For each case, the childbirth circumstances, the affected side, the different
      injuries observed such as ocular, orbital, cranial and even cerebral lesions, and
      the results of the ophthalmological follow-up examinations were recorded.
      RESULTS: In most cases, lesions resulted from forceps traumatisms, and the
      injuries were corneal (vertical tears in the Descemet's membrane), retinal
      (hemorrhages), and orbital (e.g., the optical nerve and oculomotor nerve).
      CONCLUSION: These injuries, sometimes severe, must benefit from early and
      complete examination, possibly with general anesthesia, and long-term follow-up.
      Furthermore, a radiographic and clinical neurological examination is recommended
      to prevent any cerebral complication.

PMID- 15557860
TI  - [Analysis of optic nerve head by confocal scanning laser ophthalmoscope in ocular
      hypertension].
AB  - PURPOSE: To analyze optic nerve head topography using confocal the scanning laser
      ophthalmoscope (CSLO) in ocular hypertension in comparison to normal eyes.
      PATIENTS AND METHODS: We examined 25 patients with ocular hypertension and 27
      normal controls. All of them had a complete ophthalmic examination. Optic nerve
      head analysis was performed by using a CSLO-type Heidelberg retina tomograph
      (HRT). The following stereometric parameters were evaluated: disc area, area and
      volume of cup, cup/disc ratio, area and volume of neuroretinal rim, mean and
      maximal cup depth, cup shape measure, height variation contour, mean retinal
      nerve fiber layer thickness, and retinal nerve fiber layer (RNFL) cross-section
      area. RESULTS: In ocular hypertension eyes, rim volume, height variation contour
      and RNFL thickness showed a statistically significant reduction compared to
      normal eyes. CONCLUSION: HRT appears to be an important tool in detecting early
      damage of retinal nerve fiber layer in ocular hypertension.

PMID- 15557861
TI  - Assessment of macular function by multifocal electroretinogram in age-related
      macular degeneration before and after photodynamic therapy.
AB  - PURPOSE: To evaluate macular function, before and after photodynamic therapy
      (PDT) using multifocal electroretinogram (MF-ERG), in eyes suffering from classic
      subfoveal choroidal neovascularization (CNV) resulting from age-related macular
      degeneration (ARMD). METHODS: Twenty eyes of 20 patients (10 male, 10 female)
      with classic subfoveal CNV resulting from ARMD were studied. All received PDT
      with verteporfin. Fluorescein angiography and mF-ERG were performed in each
      patient 1 day before and 1 week, 3 months and 6 months after photodynamic
      therapy. RESULTS: Before treatment, visual acuity (VA) and electrical retinal
      response densities (RRD) in the foveal and parafoveal areas were low in all
      patients. The mean VA (ETDRS chart) before PDT was 24.35 (SD, 15). The mean RRD
      before PDT in area 1 was 4.39 nV/deg(2) (SD, 2.59) and in area 2 it was 2.11 (SD,
      1.86). Six months after treatment, the mean VA was stable in 70% of the patients.
      However, the mean RRD after PDT was 2.24 nV/deg(2) in area 1 (SD, 2.59) and 1.07
      nV/deg(2) in area 2 (SD, 1.59). CONCLUSION: Multifocal ERG objectively evaluates
      the macular function in eyes with CNV attributable to ARMD. In this study, the
      stability of VA coincided with a clear impairment of electrical activity of the
      foveal and parafoveal areas. This finding suggests that MF-ERG should be adopted
      to assess the efficacy of PDT objectively in the treatment of ARMD.

PMID- 15557862
TI  - [Electroretinogram "b" wave varies with the posology of the antimalarial
      treatment].
AB  - INTRODUCTION: The electroretinogram (ERG) is currently, together with the central
      visual field test, color vision test and electroculogram (EOG), an examination
      dedicated to prevent retinopathy due to hydroxychloroquine (HCQ) or chloroquine
      (CQ) intoxication. MATERIAL AND METHODS: Thirty-two patients on treatment with
      HCQ were studied. Each patient had underwent a complete clinical ophthalmological
      examination and a set of paraclinical examinations including at least an ERG. All
      the patients were requested to decrease or stop their HCQ treatment. Following
      this change, a second ERG was recorded for each patient. The ERGs before and
      after stopping HCQ treatment were compared. We noted a statistically significant
      increase in the amplitude of "b" wave of the ERG, following after decrease or
      discontinuation of HCQ treatment. DISCUSSION AND CONCLUSION: This study has
      demonstrated the ERG "b" wave sensitivity due to the variation of HCQ
      consumption. The amplitude and the culmination time of the ERG "b" wave are
      important parameters to monitor during long term treatment with HCQ. A decrease
      of the "b" wave amplitude, coupled with an increase of its culmination time in a
      patient on long term HCQ treatment showing for the same daily dose, shall be a
      sign of alert, imposing the performance of additional visual functional tests and
      leading a decrease or a discontinuation of the treatment with HCQ. The ERG is an
      objective examination, which needs almost no participation from the patient. Its
      usefulness has been demonstrated, for the prevention of retinopathy due to
      hydroxychloroquine or chloroquine intoxication in condition that successive ERGs
      of the same patient are precisely compared.

PMID- 15557863
TI  - [Vogt-Koyanagi-Harada Disease: clinical features, therapy and long-term visual
      outcome in a Caucasian and African population].
AB  - PURPOSE: Seventeen consecutive cases of Vogt-Koyanagi-Harada (VKH) disease were
      studied to determine their clinical profile. METHODS: This was a retrospective
      study of 17 cases, in a white and African population. RESULTS: The sex ratio
      (female/male) was 1.6. Mean age was 37.65 +/- 10.2 years. Eight patients were
      Caucasian (47%), and seven were from North Africa (41%), and two were black
      Africans (12%). Eleven patients were referred during the acute stage, and six
      patients secondarily. All patients had bilateral ocular involvement. Panuveitis
      with retinal serous detachment was the most frequent presentation (88%).
      Extraocular signs were found in 87% of the cases. Initial visual acuity was 0.29
      +/- 0.36, and final visual acuity was 0.78 +/- 0.3. Patients seen during the
      acute stage were treated with general corticotherapy. Immunosuppressive agents
      were given in 56% of the cases. CONCLUSIONS: Vogt-Koyanagi-Harada disease, in a
      Caucasian and African population, has a presentation close to that of the
      Japanese population. However, cutaneous signs are much rarer. Visual prognosis
      was generally favorable.

PMID- 15557864
TI  - [Importance of occlusion therapy for amblyopia in partial unilateral congenital
      cataracts that are discovered late].
AB  - PURPOSE: The aim of this study is to investigate the importance of occlusion
      therapy for amblyopia in patients with partial unilateral congenital cataracts
      that were discovered after 24 months of age. MATERIAL AND METHODS: A
      retrospective study was conducted on 11 patients, each of whom underwent a
      clinical examination including a cycloplegic refraction with atropine. The
      average age when the cataract was diagnosed was 35 months. The average distance
      visual acuity was 6/78 and the average near visual acuity was 35/175. Occlusion
      therapy using adhesive patches was started after refractive error correction. In
      two cases, observance was mediocre. RESULTS: Ametropia was found in every
      patient, with anisometropia in nine patients (alpha < 0.02). This anisometropia
      included an astigmatism that was always greater on the side with the cataract
      (alpha < 0.001), averaging 2.7 diopters. After occlusion therapy for amblyopia,
      the average visual acuity significantly improved to 6/22 in distance vision
      (alpha < 0.02) and 35/45 in near vision (alpha < 0.01). The average follow-up
      period was 28 months (5-60 months). CONCLUSION: Amblyopia is related to lens
      opacities as well as frequently associated anisometropia. Functional improvement
      is greater in near vision than in distance vision. With occlusion therapy for
      amblyopia, accommodation is preserved. This factor is of utmost importance as
      near vision is preferential in young children. This study provides an opportunity
      to recall the importance of refraction and occlusion therapy for amblyopia, which
      must be systematically attempted in cases of partial unilateral congenital
      cataracts before considering a surgical procedure.

PMID- 15557865
TI  - [Retinopathy as a sickle-cell trait: myth or reality?].
AB  - INTRODUCTION: The retinopathy of sickle cell diseases is an ischemic retinopathy
      that occurs frequently in the major forms of HbSS and HbSC sickle cell diseases.
      The retinopathy of sickle trait HbAS has not been described extensively. PATIENTS
      AND METHODS: The aim of this study was to describe the retinal characteristics
      and thus gain better knowledge of sickle trait HbAS retinopathy. Seventy HbAS
      patients had a complete ocular examination including fluorescein angiography.
      RESULTS: Seventy percent of the patients had retinal lesions, with 49.3% non
      vasoproliferative lesions, 22.7% prevasoproliferative lesions and 2.7%
      neovascular lesions. DISCUSSION AND CONCLUSION: Retinopathy is associated with
      the HbAS sickle cell trait, but it is less serious than in the major forms of
      sickle cell syndrome.

PMID- 15557866
TI  - [Compared progression of visual-evoked potentials in preterm and term newborns].
AB  - PURPOSE: To compare the development of the visual pathway in healthy preterm and
      full-term newborns using flash and patterned (both transient and steady-state)
      visual-evoked potentials (fVEP, pVEP-t, pVEP-ss). PATIENTS AND METHODS: Twenty
      nine preterm newborns (28-35 weeks gestational age) were evaluated at four
      different times: at 3 months postnatal and corrected age, at 8 months postnatal
      and corrected age. They were matched with 92 term newborns tested at 3 and 8
      months of life. RESULTS: The maximal perceived spatial frequencies in the groups
      were: 2 C/d at 3 months postnatal age, >2 C/d at 3 months corrected age and at 3
      months at term, between 3 and 5C/d, >=5C/d at 8 months corrected age and at 8
      months of life, respectively. The latencies of the P1 and P100 waves for the
      flash and the transient stimulation were, respectively, 192 ms and 207.9 ms at 3
      months postnatal age, 144 ms and 137.7 ms at 3 months corrected age, 126.3 ms and
      124.1 ms at 8 months postnatal age, 112.7 ms and 112.5 ms at 8 months corrected
      age, 137.3 and 110.1 ms at 3 months of life; and 122.3 and 100.5 ms at 8 months
      of life. DISCUSSION: In the preterm infants of 3 gestational months, the
      latencies of the fVEP are comparable to those of the 3-month-old full-term
      infants, although the pVEP-t latencies are still delayed at 8 months. In the
      fVEP; however, we noted a shorter latency in the preterm infants at 8 months
      corrected age compared to those of the full-term infants. This tendency inversion
      was also evidenced at the steady-state stimulation. CONCLUSIONS: As evidenced by
      our results, at 8 months of corrected age the preterm infants recovered the fVEP
      and pVEP-ss, but not the pVEP-t. Different results obtained with different visual
      evoked stimulations suggest that similar neural pools are developed in not
      completely equal amounts of time.

PMID- 15557867
TI  - [Nasal fossae hemangiopericytoma revealed by acute dacryocystitis].
AB  - We report a 42-year-old woman with a hemangiopericytoma tumor located in nasal
      fossae, revealed by acute dacryocystitis. Clinical rhinoscopic examination and
      orbitofacial tomodensitometry showed tumefaction of the lacrimal sac and
      nasolacrimal duct. We removed the tumor by endonasal surgery. The
      anatomopathology examination confirmed the diagnosis of hemangiopericytoma. The
      internal canthus area and the maxillary sinus roof were treated with
      complementary irradiation.

PMID- 15557868
TI  - [Bulbar subconjunctival tumor secondary to periocular schistosome granuloma].
AB  - INTRODUCTION: Schistosomiasis, a parasitic disease, is endemic in many areas in
      the world. Schistosome eggs can be found in human tissues or organs, including
      the eye. These eggs can produce inflammatory granuloma. We report a unique and
      exceptional clinical case of periocular localization of schistosome granuloma.
      OBSERVATION: A 12-year-old girl, living in a schistosomiasis-endemic region,
      presented an inflammatory subconjunctival tumor in one eye. This tumor regressed
      but did not completely disappear with treatment. Complementary tests showed a
      slight eosinophilia (500/mm(3)) in the blood and S. mansoni ova in the stools. A
      biopsy was performed, revealing an inflammatory granuloma with epithelioid and
      giant cells rich in eosinophilic polynuclear. The immunohistochemical study
      showed no cells with anti-CD1 and anti-CD30, excluding histocytosis X type
      lesion. CONCLUSION: Although considered as exceptional, periocular localization
      of schistosome granuloma must be proposed, based on epidemiological, clinical and
      paraclinical results. Schistosomiasis may be considered as an origin of an
      inflammatory subconjunctival tumor found in endemic areas.

PMID- 15557869
TI  - [Hemolymphangioma of the orbit in a young girl: a clinical observation].
AB  - We report the clinical observation of an 8-year-old girl, admitted for a
      supermedial swelling of the eyelid associated with acute exophthalmia. The
      anatomical-pathological examination and the X-ray of the orbit provided the
      diagnosis of hemolymphangioma in a country where investigative resources are very
      limited (tomodensitometry, magnetic resonance imaging, and color Doppler). Most
      authors emphasize the advantages of MRI, which can show whether the ocular
      muscles in contact with the tumor are intact, rule out other causes of orbital
      tumors responsible for exophthalmia, and can help adjust treatment.

PMID- 15557870
TI  - [Pharmacological adjuvants for surgical treatment of proliferative
      vitreoretinopathy].
AB  - Proliferative vitreoretinopathy (PVR) is the major cause of retinal detachment
      surgery failure. Many adjuvants were studied in vitro and on animals, some were
      studied on humans. Daunomycin seems to reduce PVR recidivism. 5-FU and steroids
      are nontoxic but their efficacy is not clear. Heparin reduced postoperative
      inflammation and seems to reduce PVR recidivism when associated with 5-FU.
      Associating heparin and steroids seems to reduce PVR in some groups of patients
      (aphakic, anterior PVR). Colchicine and retinoic acid per os are ineffective,
      silicone oil is effective as an internal tamponade but not as an adjuvant of PVR.
      Currently, no molecule has proven efficacy as an adjunctive treatment of PVR.

PMID- 15557871
TI  - [Toward monosomy 3 as the main prognosis factor of uveal melanoma: current
      cytogenetic data].
AB  - Uveal melanoma is the most frequent intraocular cancer. The recent development of
      new technologies such as microsatellite analysis and comparative genomic
      hybridization have elucidated both the cytogenetics and the natural history of
      this disease. Fifty to 60% of uveal melanomas are linked to monosomy 3, which
      appears as an early and determinant event in tumor progression. Tumors with this
      anomaly have a very poor prognosis. Recent work suggests that this category of
      uveal melanomas represents a distinct pathological entity from that associated
      with normal disomy 3. Chromosome 6 aberrations probably make up a second entry
      point into the process of carcinogenesis, while gains in 8q seem to appear later
      in the natural history of uveal melanoma because of their higher frequency in
      larger tumors. Progress in genome analysis has identified regions in chromosomes
      3, 6, and 8 as those most probably involved in tumorigenesis. It is to be hoped
      that this will soon lead to the discovery of the genes responsible.

PMID- 15557873
TI  - [Hard palate mucosal graft for posterior lamella repair].
AB  - Several techniques have been proposed for posterior lamella repair. The ideal
      gaft should be easy and safe to harvest, be lined by mucosa and be rigid enough
      to support the lower lid against retraction. Hard palate mucosal grafts meet
      these criteria. The surgical procedure is done under local or general anaesthesia
      and a graft up to a 40 x 20 mm can be harvested. Paramedian and subperiostal
      harvest is recommended, local complications are less frequent (bleeding and
      sensory lesions) and the hard palate mucosa is of better quality at this site
      (thinner graft with fewer salivary glands but rigid enough due to the periostal
      layer). Donor site complications such as local bleeding can be reduced by
      meticulous surgical technique and local postoperative care such as compression
      using a mouthguard. The main indications for hard palate mucosal graft are lower
      eyelid reconstruction and management of lower eyelid retraction.

PMID- 15557874
TI  - Safety of aggressive statin therapy.
AB  - New cholesterol guidelines will lead to use of statins more frequently and at
      higher doses. Myopathy, the most common and potentially most serious adverse
      effect, is dose-related. Rhabdomyolysis, which is rare, appears to occur at a
      similar rate with all currently marketed statins. Since it can occur without
      warning symptoms, patients who take high doses or are at high risk for other
      reasons should be monitored more closely. The possibility that statins could
      increase the incidence of some kinds of cancer in humans, as they do in animals,
      is not supported by most of the data available to date, but longer followup is
      needed.

PMID- 15557875
TI  - L-carnitine.
AB  - Although advertised on the Internet for weight loss, prevention of aging and
      enhancement of athletic and sexual performance, levocarnitine has only one well
      established indication, and that is for treatment of carnitine deficiency. In
      clinical trials, the drug also seems to have had modest effects in some other
      conditions, particularly intermittent claudication and recovery after myocardial
      infarction, but more studies are needed.

PMID- 15557876
TI  - Drugs for tuberculosis.

PMID- 15557877
TI  - [The mast cells phagocytose bacteria].
AB  - In the last years there has been a growing number of reports concerning the role
      of mast cells in host defense against bacteria. The mast cell membrane is replete
      with many receptors/molecules, including those that promote the recognition and
      binding of bacteria. Mast cells exhibit two basic mechanisms of microbial
      recognition: opsonin-dependent (via Fc and C3 receptors) and opsonin-independent
      (via integrins, CD48 molecule and Toll-like receptors). Moreover, mast cells
      phagocytose and kill adherent bacteria. Phagocytosis of bacteria results in the
      presentation of bacterial antigens for MHC class I to T cells.

PMID- 15557878
TI  - Neurosurgery in the law court.
AB  - AIM: The evident rise in the number of neurosurgical malpractice and the apparent
      lack of adequate training in neurosurgery patient management are discussed.
      However, alongside neurosurgeons, neurosurgical malpractice claims involve also
      physicians from primary to specialist care, particularly those attending
      neurosurgical patients in emergency rooms. Some pathologies and disputed
      treatments are described. METHODS: The case series includes 138 medical
      malpractice lawsuits examined over a 10-year period (1992-2002). The pathologies
      for which disputed treatment led to malpractice lawsuit as well as their
      frequency are presented. RESULTS: Of the total 138 lawsuits examined, 38 did not
      involve professional health care workers, whereas the remaining 100 cases
      involved: neurosurgeons (48 cases); other specialist or primary physicians (51
      cases); nursing staff (1 case). These malpractice lawsuits and the relevant
      pathologies are examined in detail. CONCLUSION: On the basis of personal
      experience, some considerations and recommendations are suggested for the
      clinical practice.

PMID- 15557879
TI  - Surgical treatment of common peroneal nerve injuries: indications and results. A
      series of 62 cases.
AB  - AIM: Common peroneal nerve (CPN) injuries represent the most common nerve lesions
      of the lower limb and can be due to several causative mechanisms. Although in
      most cases they recover spontaneously, an irreversible damage of the nerve is
      also likely to occur. Nerve regeneration following CPN repair is poorer if
      compared to other peripheral nerves and this can explain the reluctant attitude
      of many physicians towards the surgical treatment of these patients. Among the
      several factors advocated to explain the poor outcome following surgery, it has
      been suggested that reinnervation might be obstacled by the force imbalance
      between the functioning flexors and the paralysed extensors that eventually
      results in the fixed equinism of the foot, due to the excessive contracture of
      the active muscles and the shortening of the heel cord. Therefore the early
      correction of these forces might favour nerve regeneration. Following such
      hypothesis, the authors treat irreversible CPN injuries performing a one-stage
      procedure of nerve repair and tibialis tendon transfer. We report our experience,
      describing the indications to surgical treatment, the operative technique and the
      postoperative clinical outcome correlated with the causative mechanisms of the
      injuries. METHODS: A 62-patient series controlled over a period of 15 years with
      a post-traumatic palsy of the CPN is reported. All the patients underwent
      surgery. In open wounds, when a nerve transection was suspected, surgery was
      performed at emergency (2 cases). In closed injuries, operative treatment was
      advised when no spontaneous regeneration occurred 3-4 months after the injury.
      From 1988 till 1991, 9 patients were elected for surgery : in 6 cases treatment
      consisted of neuroma resection and nerve repair by means of a graft. In 3
      patients it was performed only a CPN decompression at the fibular neck. Since
      1991, surgical treatment has always consisted of nerve repair associated with a
      tendon transfer during the same procedure. Fifty-three patients were elected for
      surgery. Nerve repair was achieved by direct suture in 1 case and by means of a
      graft in 46 patients. Decompression of the CPN at the fibular neck was performed
      in 6 patients where nerve continuity was demonstrated. RESULTS: In the first
      group of patients, nerve repair outcome was highly disapponting: no recovery in 5
      cases, reinnervation occurred in 1 patient only (M1-2). CPN decompression was
      followed by complete recovery in 2 cases, no improvement was observed in 1 case.
      Nerve repair associated with tibialis tendon transfer dramatically improved the
      postoperative outcome: at 2 year follow-up, neural regeneration was demonstrated
      in 90% of the patients. Surgical outcome depends on the causative mechanisms of
      the lesion: sharp injuries and severe dislocations of the knee had an excellent
      recovery, while in crush injuries and gunshot wounds good recovery was less
      common. CONCLUSION: Surgical treatment of CPN injuries can nowadays be highly
      rewarding. CPN palsies in open wounds should undergo surgical exploration at
      emergency. In close injuries with no spontaneous recovery within 4 months after
      the injury, patients should be advised to seek surgical treatment regardless the
      causative mechanism of the lesion. According to our experience, the association
      of a transfer procedure to nerve repair enhances neural regeneration,
      dramatically improving the surgical outcome of these injuries.

PMID- 15557880
TI  - Anterior submuscular transposition of the ulnar nerve in severe cubital tunnel
      syndrome. Personal experience.
AB  - AIM: The authors report the results of anterior submuscular transposition, on a
      clinical series of selected patients with severe cubital tunnel syndrome. In
      these patients, the degree of ulnar nerve compression was valued using a grading
      system that includes measurements of motor and sensitive function. In this
      series, a technique of flexor-pronator mass Z-lengthening was adopted. METHODS:
      From 1998 to 2002, 18 patients were surgically treated with anterior deep
      submuscular transposition for cubital tunnel syndrome. The preoperative status
      was determined using Dellon's classification. Fifteen out of 18 patients were
      graded as Dellon's grade 3 (severe syndrome). The mean duration of follow-up
      after surgery was 27.6 months. RESULTS: Postoperative outcome was assessed in all
      the 15 patients according to a modified Bishop scoring system. Based on this
      score, 6 patients (40%) were graded as excellent, 7 (47%) were graded as good and
      2 (13%) were graded as fair. The complete recovery occurred about 6 months after
      surgery. None complication was observed. CONCLUSION: Treatment of severe cubital
      syndrome by means of a technique of flexor-pronator mass Z-lengthening was linked
      to 87% rate of good to excellent results. The present study demonstrate the
      feasibility of this technique with restitutio ad integrum in spite of the
      severity of the syndrome. None failure nor recurrence was present in this series.

PMID- 15557881
TI  - Lymphoplasmacyte rich meningioma. A case report and review of the literature.
AB  - A peculiar type of meningioma with conspicious plasma-cell components is
      described. In accordance with the World Health Organization's Histological Typing
      of Tumours of the Central Nervous System, this rare clinical entity is recently
      designed as lymphoplasmacyte rich (LPR) meningioma. This type of meningioma is
      usually accompanied by prominent peripheral blood abnormalities, anemia and/or
      policlonal gammophaty, that disappear after surgical removal of the tumor.
      Actually, the origin (neoplastic or inflammatory) of this tumor is unclear; its
      biological behavior and clinical course are anomalous so it is considered closer
      to intracranial inflammatory masses rather than typical meningioma. In this
      paper, a new case of intracranial LPR meningioma occurring in a woman, is
      reported and a review the literature is made.

PMID- 15557882
TI  - Anterior cervicothoracic meningocele treated by cystopleural shunt. Case report
      and review of the literature.
AB  - Anterior meningocele is a rare disease which is commonly observed in the sacral
      region. Anterio cervicothoracic meningocele is generally diagnosed in adult age
      and there are few reports in infancy. Different treatment procedures are
      performed such as ligation, resection and wrapping. The case of a 9-month-old
      male infant with acute respiratory distress and cyanosis is described. He had
      also recurrent lung infections for 3 months. The magnetic resonance imaging
      revealed an anterior cervicothoracic meningocele which was compressing the lung,
      aorta, esophagus and trachea associated with skeletal abnormalities and C2 - C7
      syringohydromyelia. There was no evidence of neurofibromatosis. He was submitted
      to thoracotomy and treated with cystopleural shunt without valve system.
      Postoperatively his respiratory distress improved dramatically. Radiologically,
      the size of meningocele decreased and the syringomyelic cavity disappeared. There
      was no evidence of recurrence during his followup. Cystopleural shunt procedure
      is a reliable, simple and effective treatment modality in anterior
      cervicothoracic meningocele cases. This treatment regimen prevents possible
      neural damage and also treatments to the associated anomalies such as
      syringohydromyelia.

PMID- 15557883
TI  - Multiple sclerosis and gliomas. Clinical remarks on 10 cases and critical review
      of the literature.
AB  - The association between multiple sclerosis and tumours of the central nervous
      system is unusual. The authors analyzed the clinico-pathological elements of the
      correlation. The pertinent literature on this subject is critically reviewed. Ten
      cases of patients with an history of multiple sclerosis for more than 15 years
      and a clinical and radiological evidence of brain tumour were submitted to
      surgery in order to remove the lesion and/or to chemo- and radiotherapy. The
      various aspects of the association were studied in detail. A patient with
      multiple sclerosis, particularly with atypical symptoms, should be evaluated by
      an annual MRI investigation with intravenous paramagnetic contrast medium. The
      diagnostic work-up should be: clinical and radiological assessment; MRI in the
      event of atypical symptoms; Sstereotactic or neuronavigation-aided biopsy in any
      suspected lesions. Patients with multiple sclerosis and glioma present survival
      times identical to those observed in patients not suffering from multiple
      sclerosis. The coexistence of multiple sclerosis and brain tumours does not seem
      to influence the clinical evolution of either of these pathologies. We believe
      that it is important to achieve an early diagnosis of brain tumour in such
      patients with a clinical and neuroradiological follow up, so that they can be
      treated promptly.

PMID- 15557884
TI  - Prophylaxis to avert exacerbation/relapse of multiple sclerosis in affected
      patients undergoing surgery. Surgical observations and recommendations.
AB  - To provide the neurological and neurosurgical communities with case evidence of
      postoperative multiple sclerosis (MS) relapse, literature review to support
      operative stress-induced relapse and recommendations for perioperative
      prophylaxis to prevent relapse in patients undergoing surgery. Two case studies
      are presented with recommendations based on an extensive review of the medical
      literature and personal experience to support perioperative prophylactic
      suggestions. Both patients fully recovered to preoperative functional status
      after treatment. We now routinely implement perioperative prophylaxis to MS
      patients undergoing surgery at our institution with no complications to date.
      Perioperative prophylaxis in patients with MS undergoing surgery can prevent
      relapse. It is of utmost importance that the surgical community realizes that
      prophylactic treatment is available and should be utilized during elective and
      emergent surgical situations.

PMID- 15557885
TI  - Cauda equina melanoma presenting with subarachnoid hemorrhage. A case report.
AB  - The case of a 57-year-old woman with a primary melanoma of the cauda equina is
      reported. The peculiarity of the case is the very rare clinical presentation
      mimicking a subarachnoid hemorrhage. The patient underwent surgical excision of
      the mass. The clinicopathological and neuroradiological features are summarized.

PMID- 15557886
TI  - Reconstruction of a large post-traumatic cranial defect with a customized
      titanium plaque.
AB  - The treatment of serious cranial defects has always been a fascinating and
      controversial issue for craniofacial surgeons and in the last years many
      solutions have been proposed. One of the most effective method is a personalized
      titanium plaque prepared by processing anatomical data obtained with a CAT of the
      patient. A case of wide cranial defect on the left fronto-parietal region in a 56
      year-old man treated with a personalized titanium plaque obtained by processing
      the data of a spiral CAT of the skull is described. No complications were
      observed in the postoperative course and follow-up after 6 moths showed that the
      patient was in good general condition.

PMID- 15557895
TI  - Clinical effect of abdominal aortic aneurysm endografting: 7-year concurrent
      comparison with open repair.
AB  - OBJECTIVE: We compared the effectiveness and clinical outcome of open repair
      versus endovascular aortic aneurysm repair (EVAR) in achieving prevention of
      abdominal aortic aneurysm (AAA)-related death and graft-related complications.
      METHODS: Over 7 years from 1997 to 2003, 1119 consecutive patients underwent
      elective treatment of infrarenal AAAs, 585 with open repair and 534 with EVAR.
      Patients were regularly followed up at 1, 6, 12 months, and every 6 months
      thereafter, in EVAR group, and at 3 and 12 months, and yearly thereafter after
      open repair. Preoperative, intraoperative, and follow-up data were stored in a
      prospective database. RESULTS: Median follow-up was similar in the 2 groups: 33
      months (interquartile range [IQR], 13-50 months) in the EVAR group vs 35 months
      (IQR, 15-54 months) in the open repair group. EVAR group patients were older than
      patients in the open repair group: 73 years vs 72 years (P = .04). There were
      statistical significant differences between the EVAR group and the open repair
      group with respect to AAA median diameter (52 mm vs 56 mm), coronary disease rate
      (46% vs 37%; P = .001), pulmonary disease rate (56% vs 38%; P < .0001), and
      American Society of Anesthesiologists IV score rate (16% vs 6%; P < .0001).
      Thirty-day mortality in the EVAR group was 0.9% (5 of 534 patients), compared
      with 4.1% (24 of 585 patients; P = .001) in the open repair group, and major
      morbidity was 9.1% (49 of 534 patients) vs 18.6% (109 of 585 patients; P <
      .0001), respectively. The incidence of secondary procedures in the EVAR group was
      15.7%, compared with 3% in the open repair group (P < .0001). There were no
      deaths related to secondary procedures in either group. Six AAAs (1.1%) ruptured
      after EVAR, 3 of which were fatal; in the open repair group 1 patient (0.2%)
      underwent successful repeat operatation to treat iliac pseudoaneurysm rupture 5
      years after the original procedure. Kaplan-Meier estimates for freedom from
      aneurysm-related death at 84 months were 97.5% in the EVAR group and 95.9% in the
      open repair group (log rank test, P = .008). Kaplan-Meier survival estimates at
      84 months were 67.1% in the open repair group and 66.9% in the EVAR group (P =
      NS). At the same interval the risk for secondary procedures was 49.4% for the
      EVAR group and 7.1% for the open repair group. Of the 11 variables analyzed with
      logistic analysis, open surgery (hazard ratio [HR], 11; 95% confidence interval
      [CI], 2.5-54.2; P = .002), American Society of Anesthesiologists IV score (HR,
      7.1; 95% CI, 2.7-18.8; P = .0001), and age (HR, 1.06; 95% CI, 1.04-1.13; P = .04)
      were positive independent predictors of perioperative mortality. CONCLUSION: Our
      data suggest that at a maximum follow-up of 7 years, patients who undergo EVAR
      show lower perioperative and late aneurysm-related mortality compared with a
      younger and substantially healthier group of patients with aneurysms treated with
      open repair. The higher need for secondary procedures in the endovascular group
      did not affect superiority of the overall performance of EVAR in the early and
      late intervals.

PMID- 15557896
TI  - Midterm results of the multicenter trial of the powerlink bifurcated system for
      endovascular aortic aneurysm repair.
AB  - PURPOSE: We assessed the results of abdominal aortic aneurysm (AAA) repair with
      the Powerlink bifurcated endovascular graft compared with open AAA repair.
      METHOD: A prospective controlled multicenter trial of the Powerlink system for
      endovascular aneurysm repair was conducted at 15 sites as part of a pivotal US
      Food and Drug Administration trial. Between July 2000 and March 2003, 258
      patients (192 test patients, 66 control patients) were enrolled. Stent grafts
      were oversized by 10% to 20% relative to computed tomography scan (CT)-based
      diameter measurements. All repairs were performed in the operating room through 1
      surgically exposed femoral artery and a contralateral 9F sheath percutaneously
      placed. Results were assessed with contrast material-enhanced CT scans and plain
      abdominal x-ray studies at 1, 6, and 12 months, and annually postoperatively.
      RESULTS: Patients were followed up for a mean of 22 months (median, 24 months).
      Technical success was achieved in 97.9% of patients, with 4 failed insertions (3
      early conversions because of deployment issues, 1 access failure). There were no
      significant differences in mortality between the Powerlink and control groups,
      and only 1 death was procedure-related. Blood loss (341 mL vs 1583 mL; P <
      .0001), operative time (136 minutes vs 222 minutes; P < .0001), intensive care
      unit stay (0.78 days vs 4.1 days; P < .0001), and hospital length of stay (3.3
      days vs 9.5 days; P < .0001) were significantly less in the Powerlink cohort
      compared with the control group. There were significantly fewer adverse events
      (myocardial infarction, P = .0131; renal failure, P = .0042; gastrointestinal
      complications, P = .0125) in the perioperative period in the Powerlink cohort
      compared with the control group, but in the longer follow-up interval adverse
      event-free survival was equivalent between groups (P = .456, log-rank test). At
      the time of the first-month CT scan, endoleaks were noted in 25 patients,
      yielding a 30-day endoleak rate of 22.7%. Type II endoleaks predominated, and
      there were no type III or IV endoleaks. Secondary procedures were performed in 19
      patients (10%), for treatment of endoleak (n = 10), limb obstruction (n = 7), and
      other causes (n = 2). There were 3 graft migrations (2.2%), 1 of which resulted
      in an endoleak. There were no ruptures, graft fabric defects, or wire fractures.
      Significant reduction in mean AAA diameter and volume was noted at every follow
      up interval. Increase in AAA diameter was noted in only 1.5% of patients at 24
      months. CONCLUSION: The Powerlink system appears safe, and effectively protects
      patients from AAA rupture over the intermediate term. The graft and stent
      materials have thus far been free from failure and fatigue. Percutaneous
      contralateral limb access facilitates graft placement in patients with
      disadvantaged access routes. Endovascular aneurysm repair with the Powerlink
      system produces significantly fewer early adverse events compared with open AAA
      repair, but mortality is equivalent with both procedures. Careful follow-up over
      the longer term is necessary to ensure the durability of these results.

PMID- 15557897
TI  - Rupture of abdominal aortic aneurysm: concurrent comparison of outcome of those
      occurring after endovascular repair versus those occurring without previous
      treatment in an 11-year single-center experience.
AB  - OBJECTIVE: The purpose of this single-center study was to compare findings at
      presentation and surgical outcome in patients in whom abdominal aortic aneurysms
      (AAAs) ruptured after endovascular repair and patients in whom AAAs ruptured
      before any treatment, over a defined period. METHODS: From May 1992 to September
      2003, 1043 patients underwent elective repair of intact infrarenal AAAs.
      Endovascular repair was performed in 609 patients, and open repair in 434
      patients. Eighteen of 609 patients (3%) who underwent endovascular AAA repair
      required treatment because of rupture of the aneurysm after a mean of 29 months
      (group 1). During the same 11-year period, another 91 patients without previous
      treatment required urgent repair of a ruptured AAA (group 2). Rupture was
      diagnosed at contrast material-enhanced computed tomography or by presence of
      extramural extravasation of blood at open repair. Except for a higher incidence
      of women in group 2, patients in both groups were similar with regard to
      demographics and clinical characteristics but differed in findings at
      presentation. Eight patients in group 1 had a known endoleak before AAA rupture,
      whereas contrast-enhanced computed tomography, performed in 15 patients at
      presentation, demonstrated an endoleak in all. Hypotension (systolic blood
      pressure <100 mm Hg) was noted at presentation in 4 of 18 patients (22%) in group
      1 and 76 of 91 patients (84%) in group 2. All patients underwent open repair via
      a transperitoneal approach, except for 4 patients in group 1 and 3 patients in
      group 2 who underwent endovascular repair of ruptured AAAs. RESULTS: The
      proportion of patients with hypotension at presentation in group 1 (4 of 18) was
      significantly less than in group 2 (76 of 91; P < .01). The difference in
      perioperative (30 day) mortality rate in group 1 (3 of 18; 16.6%) compared with
      group 2 (49 of 91; 53.8%) was also significant (P < .01). The outcome in group 1
      was therefore superior to that in group 2. CONCLUSIONS: This study confirms that
      endovascular AAA repair complicated by endoleak does not prevent rupture. The
      data suggest, however, that rupture, when it occurs in these circumstances, may
      not be accompanied by such major hemodynamic changes and high mortality as
      rupture of an untreated AAA. Further long-term follow-up and analysis in a larger
      group of patients are required to confirm the apparent intermediate level of
      protection afforded by failed endovascular repair, which does not prevent rupture
      but enhances survival after operation to treat rupture, possibly by ameliorating
      the hemodynamic changes associated with the rupture process.

PMID- 15557898
TI  - Embolization as cause of bowel ischemia after endovascular abdominal aortic
      aneurysm repair.
AB  - OBJECTIVE: We investigated the incidence, cause, and outcome of large bowel and
      small bowel ischemia after endovascular abdominal aortic aneurysm (AAA) repair.
      METHODS: Medical records for all patients undergoing endovascular AAA repair from
      December 1999 to December 2003 were reviewed. The incidence, cause, and outcome
      of clinically detected postoperative bowel ischemia were analyzed. RESULTS: Seven
      hundred two endovascular AAA repairs were performed. In 10 patients (1.4%) acute
      bowel ischemia developed. Six of these patients sustained concurrent small bowel
      necrosis, and the remaining 4 had isolated colon ischemia. Seven patients
      underwent exploratory laparotomy. In 6 of these bowel resection was performed,
      and in 1 patient the ischemic bowel was unsalvageable. Of the 6 patients with
      small and large bowel ischemia, 4 had segmental or patchy necrosis, which was
      separated by normal-appearing intestine, and 1 had extensive ischemia that
      involved most of the small bowel and the entire colon, with pathologic evidence
      of microembolization. Three patients had preoperative occlusion of the inferior
      mesenteric artery. One had unilateral and 1 had bilateral hypogastric artery
      interruption. Five of the 6 patients with small bowel ischemia had thrombus or
      atheroma in the proximal aneurysmal necks. All patients with isolated colon
      ischemia survived. All 6 patients with concurrent small bowel ischemia died.
      CONCLUSION: The total incidence of clinically evident bowel ischemia after
      endovascular AAA repair is similar to that after open surgery. However, small
      bowel ischemia occurs more commonly in patients with endovascular repair, and is
      associated with extremely high mortality. The direct pathologic evidence and the
      patterns of segmental, skipped, or patchy ischemia in most patients imply that
      microembolization has an important role.

PMID- 15557899
TI  - Surgical versus endovascular treatment of traumatic thoracic aortic rupture.
AB  - OBJECTIVES: Blunt traumatic thoracic aortic rupture is a life-threatening
      surgical emergency associated with high mortality and morbidity. The recent
      development of endovascular stent-graft prostheses offers a potentially less
      invasive alternative to open chest surgery, especially in patients with
      associated injuries. We sought to compare the results of conventional surgical
      repair and endovascular treatment of traumatic aortic rupture in a single center.
      METHODS: From July 1998 to January 2004, 20 patients with acute blunt traumatic
      aortic rupture underwent treatment at our institution. All patients had a lesion
      limited to the isthmus, and associated injuries. Initial management included
      fluid resuscitation, treatment of other severe associated lesions, and strict
      monitoring of blood pressure. Eleven patients (9 men, 2 women; mean age, 32
      years) underwent surgical repair, including direct suturing in 6 patients and
      graft interposition in 5 patients. Ten patients were operated on with
      cardiopulmonary support (left bypass with centrifugal pump, n = 2; extracorporeal
      circulation, n = 8). The delay between trauma and surgery was 2.6 days (range, 0
      21 days). Nine patients (8 men, 1 woman; mean age, 32 years) underwent
      endovascular treatment with commercially available devices (Excluder, n = 2;
      Talent, n = 7). In all patients 1 stent graft was deployed. In 2 patients the
      left subclavian artery was intentionally covered with the device. The delay
      between trauma and endovascular treatment was 17.8 days (range, 1-68 days).
      RESULTS: One patient in the surgical group (9.1%) died during the intervention.
      Three surgical complications occurred in 3 patients (27%), including left phrenic
      nerve palsy (n = 1), left-sided recurrent nerve palsy (n = 1), and
      hemopericardium 16 days after surgery that required a repeat intervention (n =
      1). No patient in this group had paraplegia. In the endovascular group successful
      stent-graft deployment was achieved in all patients, with no conversion to open
      repair. No patient died, and no procedure-related complications, including
      paraplegia, occurred in this group. Control computed tomography scans obtained
      within 7 days after endovascular treatment showed exclusion of pseudoaneurysm in
      all cases. Length of follow-up for endovascular treatment ranged from 3 to 41
      months (mean, 15.1 months). Computed tomography scans obtained 3 months after
      endovascular treatment showed complete disappearance of pseudoaneurysm in all
      patients. CONCLUSION: In the treatment of blunt traumatic thoracic aortic
      rupture, the immediate outcome in patients who receive endovascular stent grafts
      appears to be at least as good as observed after conventional surgical repair.
      Long-term follow-up is necessary to assess long-term effectiveness of such
      management.

PMID- 15557900
TI  - Transesophageal echocardiography-guided algorithm for stent-graft implantation in
      aortic dissection.
AB  - OBJECTIVE: Endovascular stent-graft placement is replacing traditional surgery in
      type B aortic dissection. Usually stent-graft implantation is performed under
      fluoroscopic and angiographic guidance, but this relatively new procedure is
      still burdened with some complications. We investigated the value of a developed
      algorithm based on transesophageal echocardiography (TEE) for guiding stent-graft
      implantation in type B aortic dissection. METHODS: Forty-two patients with type B
      aortic dissection (chronic in 28 patients with aneurysmal dilatation of the false
      lumen, and acute complicated in 14 patients) underwent endovascular stent-graft
      reconstruction of the descending thoracic aorta. TEE was always performed after
      angiography. TEE-induced variations of the procedure, based on the algorithm,
      were compared with initial angiography-based decisions. RESULTS: TEE was decisive
      for guidewire repositioning (not possible with fluoroscopy) from the false to the
      true lumen in 3 patients and for correct guidewire entrance in an elephant trunk
      prosthesis in another patient. After stent-graft implantation color Doppler TEE
      enabled detection of proximal peri-stent leaks in 13 patients, whereas only 6
      (46%) of the 13 leaks were detectable at angiography (P = .008). Most leaks were
      subsequently eliminated with balloon dilation or further stent grafting. Pulsed
      Doppler TEE was also useful for differentiating true leaks (13 patients) from
      Dacron porosity (7 patients). A pulsed-Doppler velocity cutoff value of 50 cm/s
      enabled differentiation of Dacron porosity (characterized by slow blood flow)
      from true peri-stent leak (fast flow). After stent-graft implantation TEE
      demonstrated new intimal tears in the thoracic aorta in 7 patients, whereas only
      2 of the 7 new tears were detectable at angiography (P = .024); in 6 of 7
      patients the new distal tears were subsequently resolved with placement of
      additional stents, whereas in a patient with Marfan syndrome new proximal tears
      determined a type I endoleak, which could not be resolved. Overall, TEE furnished
      decisive information additional to angiography in determining successful
      procedural changes in 16 of 42 patients (38%). There were no in-hospital deaths,
      and pre-discharge spiral computed tomograms showed a good outcome of stent-graft
      implantation in 37 of 42 patients (88%), with 5 residual type I endoleaks, all
      previously detected with TEE but impossible to eliminate with either balloon
      molding or further stent implantation. All but 2 patients (95%) are currently
      alive at mean follow-up of 30 +/- 18 months. CONCLUSIONS: TEE algorithm is an
      easy and useful tool in the operating room to guide correct stent-graft
      positioning in type B aortic dissection.

PMID- 15557901
TI  - Outcome of popliteal artery aneurysms after exclusion and bypass: significance of
      residual patent branches mimicking type II endoleaks.
AB  - PURPOSE: Popliteal aneurysms (PAs) often are treated with exclusion and bypass.
      However, excluded aneurysms can transmit systemic pressure from persistent flow
      through collateral arteries (endoleak), resulting in aneurysm growth and rupture.
      We used duplex ultrasound scanning for postoperative surveillance more than 2
      years after PA repair with exclusion and bypass, to determine the presence of
      flow and aneurysm growth. METHODS: From 1995 to 2001, 23 patients with 26 PAs
      (mean diameter, 3.2 cm; range, 1.6-5.6 cm) underwent surgical repair and were
      available for more than 2 years of follow-up. The popliteal artery was ligated
      proximal and distal to the aneurysm, and autogenous revascularization was
      performed. All patients who underwent PA endoaneurysmorrhaphy through a posterior
      approach were excluded from the study. During long-term follow-up, aneurysm sac
      flow and size were evaluated with duplex ultrasound scanning, computed
      tomography, or magnetic resonance angiography, and standard angiography. Patients
      with increased PA size and persistent flow were offered repair through a
      posterior approach. RESULTS: Over 7 years, 26 PAs (symptomatic, 11; asymptomatic,
      15) treated with aneurysm exclusion and bypass were available for more than 2
      years of follow-up (mean, 38 months; range, 24-78 months). In the postoperative
      period 16 PAs (62%) became thrombosed, 10 (38%) had persistent collateral flow
      through geniculate vessels, 6 (23%) increased in size, and 3 (12%) ruptured; 1
      (4%) resulted in limb loss. Operative findings for all ruptured PAs and 3 of 6
      PAs with increased sac size that underwent aneurysm sac exploration and
      endoaneurysmorrhaphy revealed retrograde flow through geniculate vessels,
      mimicking type II endoleak. CONCLUSIONS: These findings question the
      effectiveness of PA exclusion through proximal or distal ligation and bypass. In
      addition, retrograde flow into the aneurysm sac (ie, type II endoleak after
      endovascular abdominal aortic aneurysm repair) may transmit systemic pressure
      that can result in aneurysm rupture. We recommend PA treatment with aneurysm sac
      decompression and ligation of geniculate vessels whenever possible and routine
      postoperative surveillance of the excluded aneurysm sac.

PMID- 15557902
TI  - Atherothrombotic risk factor clustering in healthy male relatives of male
      patients with intermittent claudication.
AB  - OBJECTIVE: Family history is an independent risk factor for premature acute
      myocardial infarction; in contrast, familial risk for peripheral arterial disease
      (PAD) has yet to be determined. Elevated levels of hemostatic proteins are
      consistently predictive for cardiovascular risk in "healthy" subjects, and may
      cluster with underlying insulin resistance. Atherothrombotic risk factor
      clustering occurs in first-degree relatives of subjects with coronary artery
      disease and type 2 diabetes. These may contribute to the enhanced cardiovascular
      risk in these subjects, and we hypothesised that familial clustering may occur in
      PAD. The objective of this study was to measure atherothrombotic risk factors in
      healthy male first-degree relatives of men with intermittent claudication, with
      emphasis on thrombotic risk. METHODS: One hundred sixty-five healthy male first
      degree relatives were compared with control subjects matched for age, sex, and
      race (n = 165), free from a personal or family history of premature
      cardiovascular disease. Primary outcome measures were fibrinogen, von Willebrand
      factor, factor VII clotting activity (FVII:C), and factor XIII levels.
      Atherosclerotic risk factors were measured, and subjects were genotyped for
      common functional polymorphisms (factor VII r353q and fibrinogen B beta-455).
      RESULTS: Relatives had higher mean levels of fibrinogen (3.04 vs 2.89 g/L; P =
      .021), FVII:C (117% vs 104%; P = .000), factor XIII B subunit (1.11 vs 1.01
      IU/mL; P = .000), and complex (A 2 B 2 ; 1.18 vs 1.11 IU/mL; P = .021). At
      multivariate analysis the association between relative status and fibrinogen,
      FVII:C, and factor XIII B subunit levels were independent of other variables.
      CONCLUSIONS: The healthy male relatives of men with PAD have elevated levels of
      fibrinogen, factor VII, and factor XIII. Our results support the existence of
      thrombotic risk factor clustering in this population at "high risk."

PMID- 15557903
TI  - Total laparoscopic bypass for aortoiliac occlusive lesions: 93-case experience.
AB  - OBJECTIVES: We describe our experience with a new technique of total laparoscopic
      bypass surgery to treat aortoiliac occlusive lesions. MATERIAL AND METHODS: From
      November 2000 to December 2003, 93 total laparoscopic bypass procedures were
      performed to treat TASC (TransAtlantic Inter-Society Consensus document) grade C
      or D aortoiliac occlusive lesions. We also reimplanted 2 inferior mesenteric
      arteries, and performed 3 prosthesis-superior mesenteric bypasses and 2
      suprarenal aorta endarterectomies. Our technique includes a sloping right lateral
      decubitus installation, which enables a simple transperitoneal left retrocolic or
      retrorenal approach to the infrarenal abdominal aorta. In patients with a hostile
      abdomen a retroperitoneal videoscopic approach was used. Aorta-prosthesis
      laparoscopic anastomoses are performed simply, which averts any trauma to the
      suture material. RESULTS: Patients included 76 men and 17 women, with median
      patient age 61 years (range, 38-79 years). The approach to the aorta was always
      possible, in particular, in obese patients. It enabled stable aortic exposure
      during performance of the laparoscopic aorta-prosthesis anastomosis. Median
      operative time was 240 minutes (range, 150-450 minutes). Median aortic clamping
      time measured to unclamping of the first prosthetic limb was 67.5 minutes (range,
      30-135 minutes). Median duration of aorta-prosthesis anastomosis was 30 minutes
      (range, 12-90 minutes). The longest durations were mainly observed during the
      learning curve. Thirty-day postoperative mortality was 4% (4 of 93 patients). Two
      patients died of myocardial infarction. One patient with American Society of
      Anesthesiologists grade 4 disease operated on to treat critical ischemia died of
      multiple organ system failure, and 1 patient died of colonic ischemia. Major
      nonlethal postoperative complications were observed in 4 patients, and included
      lung atelectasia in 2 patients, graft infection in 1 patient operated on
      emergently to treat aortic occlusion, and secondary spleen rupture at day 5 in 1
      patient. Median hospital stay was 7 days (range, 2-57 days). With a mean follow
      up of 19 months (range, 1-37 months), complete recovery was observed in 89
      patients, and all grafts were patent. One patient had kinking of a prosthetic
      limb at the groin, and in 1 patient Staphylococcus epidermidis graft infection
      developed, which was treated with in situ replacement with a rifampin-bonded
      graft. CONCLUSION: Total laparoscopic aortic bypass is feasible. In patients with
      TASC C and D aortoiliac occlusive lesions, short-term outcomes are comparable to
      those with conventional aortic bypass. After the initial learning curve,
      laparoscopic technique may reduce the operative trauma of aortic bypass.

PMID- 15557904
TI  - Does a standardization tool to direct invasive therapy for symptomatic lower
      extremity peripheral arterial disease improve outcomes?
AB  - OBJECTIVES: While decision analysis and treatment algorithms have repeatedly been
      shown to improve quality of care in many areas of medicine, no such algorithm has
      emerged for the invasive management of lower extremity peripheral arterial
      disease. Using the best available evidence-based outcomes data, our group
      designed a standardization tool, the Lower Extremity Grading System (LEGS) score,
      which consistently directs limbs to a specific treatment on the basis of
      presentation. The purpose of this study was to examine whether use of such a tool
      improves outcomes by directing treatment of lower extremity peripheral arterial
      disease. METHODS: Over 18 months (July 2001-December 2002) our group intervened
      in 673 limbs (angioplasty, open surgery, primary limb amputation) with lower
      extremity peripheral arterial disease. During this time we developed the LEGS
      score, and implemented its prospective use for the final 362 limbs. For the
      purpose of this study, all 673 limbs were retrospectively scored with the LEGS
      score to determine the LEGS recommended best treatment. Of the 673 limbs, 551
      (81.9%) received the same treatment as recommended with LEGS and 122 (18.1%)
      received treatment contrary to LEGS. Limbs treated contrary to LEGS (cases) were
      then compared with matched control limbs (treated according to LEGS), with
      similar angiographic findings, clinical presentation, preoperative functional
      status, comorbid conditions and operative technical factors. Outcomes measured at
      6 months included arterial reconstruction patency, limb salvage, survival, and
      maintenance of ambulatory status and independent living status. Kaplan-Meier
      curves were used to assess patency, limb salvage, and survival; associated
      survival curves were compared with the log-rank test. Functional outcomes were
      compared with the Fisher exact test. RESULTS: After matching case limbs with
      control limbs, 9 limbs had no control match. Thus 113 limbs in 100 patients
      treated contrary to LEGS were compared with 113 limbs in 100 patients treated
      according to LEGS. Limbs treated contrary to LEGS resulted in significantly
      inferior outcomes at 6 months for measures of primary patency (57.5% vs 84.3%; P
      < .001), secondary patency (73.2% vs 96.2%; P < .001), limb salvage (89.7% vs
      97.2%; P = .04), and maintenance of ambulatory status (78% vs 92%; P = .02). As
      an additional finding, 29.6% (92 of 311) of interventions performed before
      implementation of the algorithm were treated contrary to LEGS, and thus contrary
      to objectively determined best therapy, compared with 8.3% (30 of 362) after LEGS
      implementation (P < .001). CONCLUSIONS: Limbs treated according to our
      standardization tool resulted in better outcomes compared with limbs treated
      contrary to the algorithm. These data suggest that routine use of an
      appropriately validated treatment standardization algorithm is capable of
      improving overall results for invasive treatment of lower extremity peripheral
      arterial disease.

PMID- 15557905
TI  - Infrainguinal vein bypass graft revision: factors affecting long-term outcome.
AB  - OBJECTIVES: We sought to determine the long-term results of revision procedures
      performed for repair of stenotic lesions in infrainguinal vein bypass grafts.
      METHODS: A retrospective review of 188 vein grafts, from a total series of 1260
      bypasses, undergoing revision of stenotic lesions between January 1, 1987, and
      December 31, 2002, at Brigham & Women's Hospital was undertaken. Lesions were
      identified by recurrence of symptoms, change in examination findings, or with
      routine duplex ultrasound graft surveillance. Demographic and medical risk
      factors, and surgical variables were analyzed with respect to patency outcomes
      after the initial graft revision, with descriptive statistics, logistic
      regression, and life table analysis. Primary and secondary patency rates were
      determined from the time of graft revision. RESULTS: Patients included 108 men
      (57%) and 80 women (42%) who underwent revision at a mean age of 67.8 years. One
      hundred thirty grafts required only a single revision, whereas 58 required
      subsequent additional revisions. Revision procedures included 99 vein patches
      (52.7%), 23 jump grafts (12.2%), 23 interposition grafts (12.2%), 8
      transpositions to new outflow vessels (4.3%), and 35 balloon angioplasty
      procedures (18.6%). During a mean follow-up of 1535 days, 5-year primary patency
      rate was 49.3% +/- 4.5% (SE) and 5-year secondary patency rate was 80.3% +/-
      3.6%. There was no difference in patency rate for different revision procedures,
      type of vein graft, indication for the original procedure, or for patients with
      diabetes mellitus or renal disease. The overall limb salvage rate was 83.2% +/-
      3.5% 5 years after graft revision. With COX proportional hazard analysis of time
      to failure of the revision procedure, the outflow level of the original bypass
      and the time of revision proved to be an important predictor of durability of the
      graft revision. Revision of popliteal bypass grafts resulted in a 60% 5-year
      primary patency rate, whereas revision of tibial grafts resulted in a 42% 5-year
      primary patency rate (P = .004; hazard ratio [HR], 2.06). Five-year secondary
      patency rates were 90% and 76%, respectively (P = .009; HR = 3.43). The timing of
      the graft revision proved an additional predictor. Grafts revised within 6 months
      of the index operation had lower primary patency than those with later revisions
      (42.9% vs 80.7%, respectively; HR = 1.754; P = .0152). CONCLUSIONS: Vein graft
      revisions offer durable patency and limb salvage rates after repair of stenotic
      infrainguinal bypass grafts. Vigilant ongoing surveillance is essential, because
      30.9% of revised grafts will develop additional lesions that will require repair.
      Tibial level bypass grafts that require early repeat intervention to treat graft
      stenosis are at particular risk for development of subsequent lesions.

PMID- 15557906
TI  - Heparin-bonded Dacron or polytetrafluorethylene for femoropopliteal bypass: five
      year results of a prospective randomized multicenter clinical trial.
AB  - OBJECTIVE: Dacron was largely abandoned for femoropopliteal bypass 30 years ago,
      because better patency rates were achieved with saphenous vein. Despite the range
      of potential prosthetics, polytetrafluoroethylne (PTFE) clearly predominates in
      current femoropopliteal practice. We compared heparin-bonded Dacron (HBD) with
      PTFE in a randomized multicenter clinical trial. METHOD: Over 28 months, 209
      patients (179 above-knee disease, 30 below-knee disease) were randomized to
      receive HBD (n = 106) or PTFE (n = 103) grafts. Aspirin, 300 mg/d, was started
      before surgery, and was continued if tolerated. RESULTS: At follow-up for a
      minimum of 5 years (mean, 76 months; range, 60-89 months), 37 patients (17.7%)
      had died with patent grafts and 121 (58%) grafts were occluded. Primary patency
      rate, measured with Kaplan-Meier survival analysis, was 46% (95% confidence
      interval [CI], 35%-57%) at year 5 for HBD, compared with 35% for PTFE (CI, 25%
      45%; P < .055). Long-term patency was achieved in only 4 of 78 interventions
      performed in 55 thrombosed grafts. Secondary patency rate for HBD was 47% (CI,
      36%-58%), and for PTFE was 36% (CI, 26%-46%). Risk factors for arterial disease
      did not significantly influence prosthetic patency. Major limb amputation was
      necessary in 9 patients with HBD grafts and 20 patients with PTFE grafts (P <
      .025). Two amputations in the HBD group and 8 amputations in the PTFE group were
      in patients undergoing bypass surgery to treat claudication only. Limb salvage
      rate was 86% (CI, 77%-95%) and 74% (CI, 64%-84%), respectively. CONCLUSIONS:
      Significantly better patency rates were achieved with HBD than with PTFE at 3
      years (P < .044), but the difference was no longer statistically significant at 5
      years (P < .055). The incidence of major limb amputation, however, was
      significantly greater (P < .025) in the PTFE group compared with the HBD group at
      both 3 and 5 years of follow-up.

PMID- 15557907
TI  - Effect of carbohydrate supplementation on walking performance in peripheral
      arterial disease: a preliminary physiologic study.
AB  - OBJECTIVE: In this preliminary study we tested the effect of short-term
      carbohydrate supplementation on carbohydrate oxidation and walking performance in
      peripheral arterial disease. METHODS: Eleven patients with peripheral arterial
      disease and intermittent claudication and 8 healthy control subjects completed
      several weeks of baseline exercise testing, then were given supplementation for 3
      days with a carbohydrate solution and placebo. Maximal walking time was assessed
      with a graded treadmill test. Carbohydrate oxidation during a submaximal phase of
      this test was measured with indirect calorimetry. At the end of baseline testing
      a biopsy specimen was taken from the gastrocnemius muscle, and the active
      fraction of pyruvate dehydrogenase complex activity was determined. RESULTS:
      Carbohydrate supplementation resulted in a significant increase in body weight
      and carbohydrate oxidation during exercise in patients with intermittent
      claudication and control subjects. Maximal walking time decreased by 3% in
      control subjects, whereas it increased by 6% in patients with intermittent
      claudication (group x treatment interaction, P < .05). There was a wide range of
      performance responses to carbohydrate supplementation among patients with
      claudication (-3%-37%). This effect was greater in poorer performers, and was
      negatively correlated (P < .05) with muscle pyruvate dehydrogenase complex
      activity. CONCLUSION: Preliminary data suggest that carbohydrate oxidation during
      exercise might contribute to exercise intolerance in more dysfunctional patients
      with intermittent claudication and that carbohydrate supplementation might be an
      effective therapeutic intervention in these patients.

PMID- 15557908
TI  - Gender differences in blood velocities across carotid stenoses.
AB  - OBJECTIVES: Carotid duplex scanning is the standard test for documenting carotid
      disease. Carotid endarterectomy effectively reduces stroke in selected patients
      with carotid artery disease. Data from large national randomized trials suggest
      that the benefits of CEA may be gender dependent. Because many diagnoses are made
      and treatment is based on the results of carotid duplex ultrasound scanning
      alone, it is important to determine whether different diagnostic thresholds
      should be used in men and women. The purpose of this study was 2-fold: to examine
      whether there is an overall gender difference in carotid velocity at similar
      arteriographic stenoses, and to determine whether there are significant
      differences at clinically relevant thresholds of disease. METHODS: A database of
      938 carotid arteriogram entries was established prospectively, with accompanying
      measurements of peak systolic velocity (PSV) and end-diastolic velocity (EDV).
      The percent of internal carotid artery stenosis seen on arteriograms was
      calculated according to criteria from the North American Symptomatic Carotid
      Endarterectomy Trial. Analyses were made in 536 carotid arteries in men and 402
      carotid arteries in women. In addition, the single most diseased artery per
      patient was analyzed by gender. PSV and EDV were averaged for data subsets
      according to 10% intervals of internal carotid artery stenoses. Velocity for each
      interval was compared between men and women with the Student t test. Receiver
      operator characteristic curves were developed to define optimal duplex criteria
      for 60% and 70% stenosis. RESULTS: For all intervals, PSV and EDV averaged 9% and
      6% higher, respectively, in women than in men. Significant gender differences
      existed between PSV and EDV for 60% and 70% stenosis (P = .03). When a single
      vessel per patient was analyzed these observations persisted, but lost
      significance for PSV at 60% stenosis (P = .18). Receiver operator characteristic
      curves at 90% sensitivity demonstrated that optimal PSV for 60% stenosis was 160
      cm/s and 180 cm/s, and for 70% stenosis was 185 cm/s and 202 cm/s, in male and
      female patients, respectively. CONCLUSIONS: Women have higher carotid blood flow
      velocity than men do. Gender differences exist, and are notably different at
      clinically relevant thresholds for intervention. These data indicate that
      different criteria should be used for interpreting carotid velocity profiles in
      women than in men, and have potentially important implications for patient care.

PMID- 15557909
TI  - Comparison of angioplasty and stenting with cerebral protection versus
      endarterectomy for treatment of internal carotid artery stenosis in elderly
      patients.
AB  - PURPOSE: Carotid angioplasty and stenting (CAS) is being evaluated as an
      alternative to carotid endarterectomy (CEA) for treatment of severe carotid
      artery stenosis. Because CAS does not require general anesthesia and is less
      traumatic, it might be especially advantageous in older patients, but data
      comparing these 2 treatment methods in older patients are scarce. METHODS: The
      periprocedural complication rates in 53 patients aged 75 years or older who had
      undergone protected CAS between June 2001 and April 2004 were compared with those
      in a group of 110 patients aged 75 years or older who had undergone CEA between
      January 1997 and December 2001, before widespread introduction of CAS procedures
      at our institution. All patients were evaluated by a neurologist both before and
      after surgery. According to the criteria set forth by the large trials the
      occurrence of minor, major, or fatal stroke, and myocardial infarction within 30
      days was determined. RESULTS: The demographic characteristics and indications for
      an intervention were similar in both treatment groups. Thirty patients (57%) in
      the CAS group had symptomatic carotid stenosis, compared with 69 patients (63%)
      in the CEA group. In neither group was there any fatal stroke or myocardial
      infarction. The 30-day stroke rate was significantly higher in the CAS group (4
      minor, 2 major strokes; 11.3%) than in the CEA group (no minor, 2 major strokes;
      1.8%; P < .05). Although the 30-day major stroke rate between CAS and CEA groups
      was comparable (3.8% vs 1.8%; P = 0.6), this effect was mainly attributable to a
      significantly higher rate of minor stroke in the CAS group (7.5% vs 0%; P < .05).
      CONCLUSION: Despite the use of cerebral protection devices the neurologic
      complication rate in patients aged 75 years and older associated with CAS was
      significantly higher than with CEA performed by highly skilled surgeons at our
      academic institution. Although this finding is mainly based on a significantly
      higher rate of minor stroke in the CAS group, the common practice of
      preferentially submitting older patients to CAS is questionable, and should be
      abandoned until the results of further randomized trials are available.

PMID- 15557910
TI  - Credentialing of surgeons as interventionalists for carotid artery stenting:
      experience from the lead-in phase of CREST.
AB  - BACKGROUND: Credentialing of vascular surgeons to perform carotid artery stenting
      (CAS) continues to be a major issue confronting the specialty of Vascular
      Surgery. Cannulation of aortic arch branches, and placement of carotid
      antiembolic devices and stents constitute the major technical challenges to
      vascular surgeons becoming credentialed to perform CAS. The multicenter Carotid
      Revascularization Endarterectomy vs Stenting Trial (CREST), supported by the
      National Institute of Neurological Disorders and Stroke, National Institute of
      Health, reviews credentials of interventionalists, including surgeons, for the
      trial's "lead-in" phase of CAS to treat symptomatic (>50% stenosis) and
      asymptomatic (>70% stenosis). METHODS: Vascular surgeons requesting participation
      in CREST must have achieved basic interventional credentialing criteria as
      recommended by the Society of Vascular Surgery. Each interventionalist is asked
      to submit notes and narrative summaries from a series of 10 to 30 CAS procedures
      for review by a multi-specialty review committee before being approved to
      participate in CREST. Thereafter, during the lead-in phase of CREST, each
      approved interventionalist is asked to perform CAS procedures using the study
      devices in as many as 20 patients. In this interim report from the CREST lead
      phase, the association of specialty of operator (vascular surgeon, neurosurgeon,
      other specialist) and periprocedural stroke and death rate was examined in
      patients undergoing CAS. In addition, current enrollment volume in the lead-in
      phase by specialty of the principal investigator was examined. RESULTS: Thirty
      two of 134 (23.9%) CREST-credentialed interventionalists are vascular surgeons (n
      = 22; 16.4%) or neurosurgeons (n = 10; 7.5%). For events monitored through March
      31, 2004, 789 patients had undergone CAS procedures performed by these 134
      specialists. Thirty-day stroke and death rate was 4.6%, and myocardial infarction
      was observed in 1.1% of patients. Serious adverse events have not been clustered
      at individual institutions, and no significant differences have been observed
      between vascular surgeons or neurosurgeons and other credentialed specialists.
      CONCLUSIONS: Vascular surgeons with basic catheter and guide wire skills,
      particularly those who have incorporated diagnostic cerebral angiography into
      their practice, can be credentialed to perform CAS. Individuals or groups should
      devote a number of cases (n = 10-30 per surgeon) to CAS to accomplish this goal.
      Pending US Food and Drug Administration approval of devices and Center for
      Medicaid and Medicare Services reimbursement, institutional financial support for
      the performance of these procedures must be secured. The learning curve for CAS
      should not be considered so formidable as to discourage surgeons from adding
      these techniques of CAS to their procedural inventory.

PMID- 15557911
TI  - Role of prophylactic temporary inferior vena cava filters placed at the ICU
      bedside under intravascular ultrasound guidance in patients with multiple trauma.
AB  - OBJECTIVE: Patients with multiple trauma often have injuries that preclude the
      use of anticoagulation therapy or sequential compression device prophylaxis.
      Temporary inferior vena cava (IVC) filters (IVCFs) offer protection against
      pulmonary embolism during the early immediate injury and perioperative period,
      when risk is highest, while averting potential long-term sequelae of permanent
      IVCFs. The objective of this study was to evaluate the efficacy of prophylactic,
      temporary IVCF placement at the intensive care unit bedside under real-time
      intravascular ultrasound (IVUS) guidance in patients with multiple trauma.
      INTERVENTIONS: Ninety-four patients with multiple trauma seen between July 1,
      2002, and November 1, 2003, underwent placement of OptEase (Cordis Endovascular)
      retrievable IVCFs under real-time IVUS guidance. Mean (+/-SD) Injury Severity
      Score was 25.1 +/- 2.2). Abdominal x-ray films were obtained in all patients to
      verify filter location. Before IVCF retrieval all patients underwent femoral vein
      color-flow ultrasound scanning to rule out deep vein thrombosis (DVT), and pre
      procedure and post-procedure vena cavography to identify possible IVCF thrombus
      entrapment and post-retrieval inferior vena cava injury. RESULTS: Nineteen
      patients died of their injuries; no deaths were related to IVCF placement. One
      pulmonary embolism occurred during follow-up after filter retrieval, and 1
      insertion site femoral vein DVT occurred. As verified on abdominal x-ray films,
      96.8% (91 of 94) of IVCFs were placed without complications at the L2-3 level.
      Filter-related complications included 2 groin hematomas (2.1%) and 3 IVCFs
      misplaced in the right iliac vein (3.2%), early in our experience; the filters
      were uneventfully retrieved and replaced in the inferior vena cava within 24
      hours. Thirty-one patients underwent uneventful retrieval of IVCFs after DVT or
      pulmonary embolism anticoagulation prophylaxis was initiated. Forty-four filters
      were not removed, 41 because severity of injury prevented DVT or pulmonary
      embolism prophylaxis and 3 because of thrombus trapped within the filter.
      CONCLUSIONS: Prophylactic, temporary IVCF placement at the intensive care unit
      bedside under IVUS guidance in patients with multiple trauma is simple and safe,
      and serves as an effective "bridge" to anticoagulation therapy until venous
      thromboembolism prophylaxis can be initiated. Further investigation of this
      bedside technique and the role of temporary IVCFs in patients with multiple
      trauma is warranted. CLINICAL RELEVANCE: Patients with multiple trauma often have
      injuries that preclude the use of anticoagulation therapy or sequential
      compression device prophylaxis. Temporary inferior vena cava filters (IVCFs)
      offer protection against pulmonary embolism during the perioperative and
      immediate injury period, when risk is highest. Ninety-four patients with multiple
      trauma underwent prophylactic, temporary IVCF placement at the intensive care
      unit bedside under real-time intravascular ultrasound. One pulmonary embolism
      occurred during follow-up after filter retrieval, and 1 insertion site femoral
      vein deep venous thrombosis occurred. Ninety-one of 94 IVCFs (96.8%) were placed
      without complication. Thirty-one patients underwent uneventful retrieval of IVCFs
      after anticoagulation prophylaxis was initiated. Forty-four filters were not
      removed, because of severity of injury (n = 41) or because of trapped thrombus
      within the filter (n = 3). Prophylactic, temporary IVCFs placed under
      intravascular ultrasound guidance at the bedside in patients with multiple trauma
      is simple, safe, and an effective bridge to anticoagulation therapy.

PMID- 15557912
TI  - Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep
      venous thrombosis: safety and feasibility study.
AB  - PURPOSE: The current standard of care for deep venous thromboembolism (DVT) is
      anticoagulation; however, this treatment method does not rapidly relieve clot
      burden or clinical symptoms. We describe a rapid and effective method of thrombus
      removal, with simultaneous percutaneous mechanical thrombectomy (PMT) and
      thrombolysis. METHODS: Over 26 months 20 patients (22 men, 2 women; mean age, 52
      +/- 6 years [range, 38-79 years]) with extensive lower extremity DVT were treated
      with PMT with the AngioJet thrombectomy device in combination with lytic agent
      (urokinase, tissue plasminogen activator, or reteplase) added to the infusion.
      Three patients underwent treatment twice, because of recurrent DVT. The primary
      end point was angiographic evidence of restoration of venous patency at
      completion of the procedure. Complications, recurrent ipsilateral DVT, and
      improvement in clinical symptoms were evaluated. RESULTS: Complete thrombus
      removal was obtained in 15 procedures (65%), and partial resolution in the
      remaining 8 procedures (35%). Inciting occlusive lesions responsible for acute
      DVT were revealed in 14 patients (61%), and angioplasty with or without stenting
      was performed when necessary. In the 8 procedures with partial resolution
      additional catheter-directed thrombolysis was carried out on average for 5.7
      hours, with further thrombus reduction. Overall, immediate (<24 hours)
      improvement in clinical symptoms was noted in 17 patients (74%). There were no
      complications related to either PMT or the short duration of lytic agent
      infusion. At average follow-up of 10.2 +/- 0.3 months (range, 3-26 months), 3
      patients had recurrent ipsilateral DVT, and underwent repeat treatment.
      CONCLUSIONS: Addition of lytic agent to PMT facilitates thrombus extraction,
      decreases overall interventional treatment time, and improves patient outcomes.
      In addition, definitive management of underlying anatomic lesions can be
      performed in the same setting. Further outcome measures are necessary to study
      the long-term efficacy of this treatment method on preservation of valve
      function, reduction of chronic venous insufficiency, and improved quality of
      life.

PMID- 15557913
TI  - Clinical and economic outcomes in thrombolytic treatment of peripheral arterial
      occlusive disease and deep venous thrombosis.
AB  - PURPOSE: Over the past 2 decades the use of thrombolytic therapy in the
      management of peripheral occlusive diseases, most notably peripheral arterial
      occlusion (PAO) and deep venous thrombosis (DVT), has become an accepted and
      potentially preferable alternative to surgery. We examined the period when
      urokinase was in short supply and subsequently unavailable, to explore potential
      differences in clinical outcome and economic effect between urokinase and
      recombinant tissue plasminogen activator (rt-PA). MATERIAL AND METHODS: Data were
      obtained from the Premier Perspective Database, a broad clinical database that
      contains information on inpatient medical practices and resource use. The study
      population included all patients hospitalized in 1999 and 2000 with a primary or
      secondary diagnosis of PAO or DVT. Incidence was calculated for common adverse
      events, including bleeding complications, intracranial hemorrhage, amputation,
      and death. Cost data were also abstracted from the database, and are expressed as
      mean +/- SD. RESULTS: Demographic variables were similar in the urokinase and rt
      PA groups. The rate of bleeding complications was similar in the urokinase and rt
      PA groups. There were no intracranial hemorrhages in the urokinase group,
      compared with a rate of 1.5% in the rt-PA PAO group (P = .087) and 1.9% in the rt
      PA DVT group (P = .175). The in-hospital mortality rate was lower in the
      urokinase-treated PAO subgroup (3.6% vs 8.5%; P = .026), but a similar finding in
      the DVT subgroup did not achieve statistical significance (4% vs 9.8%; P = .069).
      While pharmacy costs were greater in the urokinase-treated group (US 5472 dollars
      +/- US 5579 dollars vs US 3644 dollars +/- US 6009 dollars, P < .001; PAO
      subgroup, US 11,070 dollars +/- US 15,409 dollars vs US 6150 dollars +/- US
      12,398 dollars, P = .003), overall hospital costs did not differ significantly
      between the 2 groups. This finding appears to be explained by a shorter hospital
      stay and reduced room and board costs in the urokinase-treated group. CONCLUSION:
      There were significant differences in outcome in patients with PAO and DVT who
      received treatment with urokinase and rt-PA. While pharmacy costs were
      significantly greater when urokinase was used, reduction in length of stay
      accounted for similar total hospital costs compared with rt-PA. These findings
      must be considered in the context of the retrospective nature of the analysis and
      the potential to use dosing regimens that differ from those in this study.

PMID- 15557914
TI  - Choice of vascular surgery as a specialty: survey of vascular surgery residents,
      general surgery chief residents, and medical students at hospitals with vascular
      surgery training programs.
AB  - PURPOSE: Under the direction of the Association of Program Directors in Vascular
      Surgery, a survey was mailed to vascular surgery residents (VSRs), general
      surgery chief residents (GS-CRs), and fourth-year medical students (MSs) to
      better define reasons why trainees do and do not choose vascular surgery as a
      career. METHODS: Questionnaires were mailed to all accredited VSR programs and
      their associated GS programs in the United States and Canada in 2001 (survey 1)
      and in 2003 (survey 2) and to 2 medical schools with VSR programs in 2001. A
      total of 197 VSRs, 169 GS-CRs, and 78 MSs responded (overall program response
      rate of 78% for VSRs, 46% for GSRs, 20% for MSs). A scoring system was assigned,
      with 1.0 the least important and 5.0 the most important reasons to choose or not
      choose vascular surgery. RESULTS: Technical aspects, role of mentors, and complex
      decision making involved in vascular surgery were the most important reasons that
      VSRs, GS-CRs, and MSs would choose vascular surgery as a specialty (average
      scores > or =4.0 for VSRs and GS-CRs; > or =3.5 for MSs). Responses of GS-CRs and
      VSRs did not vary significantly between surveys 1 and 2, except endovascular
      capabilities of vascular surgeons had a more important role in choosing vascular
      surgery, and future loss of patients to other interventionalists had a more
      important role in not choosing this specialty in the more recent survey of GS-CRs
      and VSRs. MSs identified lifestyle as a surgical resident (4.3) and as a surgeon
      (4.2) as the most important negative factors. A training paradigm consisting of 4
      years general surgery + 2 years vascular surgery with a GS certificate was
      favored by 64% of GS-CRs and 48% of VSRs, compared with a paradigm of 5 years + 2
      years with a general surgery certificate, which was favored by 29% of GS-CRs and
      25% of VSRs, or 3 years + 3 years without a general surgery certificate, favored
      by 7% of GS-CRs and 27% of VSRs. Of note, 86% of MSs favored 3 years general
      surgery + 3 years vascular surgery or 2 years general surgery + 4 years vascular
      surgery compared with longer general surgery training periods. CONCLUSION: These
      findings may help vascular surgery program directors devise strategies to attract
      future trainees. The importance of mentorship to general surgery junior residents
      and medical students in choosing vascular surgery cannot be overestimated.
      Endovascular capabilities of vascular surgeons have an increasingly positive role
      in career choice by GS-CRs and VSRs, but these residents express increasing
      concerns about potential loss of patients to other specialists. Lifestyle
      concerns are the most important reasons why medical students do not choose
      vascular surgery as a career.

PMID- 15557915
TI  - Characterization of retrograde collateral (type II) endoleak using a new canine
      model.
AB  - OBJECTIVE: The clinical significance of retrograde collateral arterial perfusion
      of abdominal aortic aneurysms after endovascular repair (type II endoleak) has
      not been completely characterized. In this study a canine model was used to
      analyze intra-aneurysmal pressure, thrombus histologic characteristics, endoleak
      patency, and radiographic appearance of type II endoleaks originating from single
      and multiple aneurysm side branches. METHODS: Prosthetic aneurysms with an
      intraluminal solid-state strain-gauge pressure transducer were created in the
      infrarenal aorta of 14 mongrel dogs. A single collateral side branch was
      reimplanted in 4 animals, multiple side branches were reimplanted in 6 animals,
      and no side branches were reimplanted in 4 control animals. Intra-aneurysmal and
      systemic pressure was measured for 60 to 90 days after creation of the type II
      endoleak. Endoleak patency and flow were assessed with duplex ultrasound scanning
      and cine-magnetic resonance angiography. Histologic analysis of the intra
      aneurysmal thrombus was also performed. RESULTS: Stent-graft exclusion reduced
      intra-aneurysmal pressure significantly in all animals, as compared with systemic
      pressure (P < .001). All intra-aneurysmal pressure values are indexed to the
      systemic pressure, and are represented as a percentage of the simultaneously
      obtained systemic pressure, which has a value of 1.0. Type II endoleaks
      originating from multiple side branches exhibited significantly increased intra
      aneurysmal systolic pressure, mean pressure, and pulse pressure, as compared with
      endoleaks derived from either a single side branch (systolic pressure: multiple,
      0.70 +/- 0.28 vs single, 0.50 +/- 0.19; P < .001; mean pressure: multiple, 0.78
      +/- 0.23 vs single, 0.59 +/- 0.22, P < .001; pulse pressure: multiple, 0.41 +/-
      0.25 vs single, 0.17 +/- 0.15, P < .001) or excluded control aneurysms that had
      no side branches and no endoleak (systolic pressure, 0.17 +/- 0.09; mean
      pressure, 0.14 +/- 0.10; pulse pressure, 0.098 +/- 0.08; P < .001). Cine-magnetic
      resonance angiograms and duplex ultrasound scans documented persistent patency of
      multiple branch endoleaks up to the time of euthanasia. In contrast, single side
      branch endoleaks thrombosed within 3 days (P < .001). Thrombus in the aneurysm
      sac in close proximity to the endoleak contained intact red blood cells and
      limited fibrin. Thrombus distant from the endoleak demonstrated extensive fibrin
      deposition and degraded red blood cells. CONCLUSION: The canine model may be used
      to reliably measure intra-aneurysmal pressure in the presence of patent and
      thrombosed type II endoleaks. In this model 2 or more side branches are necessary
      to maintain persistent patency of type II endoleaks. These endoleaks are
      associated with significantly elevated intra-aneurysmal pressure, that is, 70% to
      80% of systemic pressure. These results suggest that persistent type II endoleaks
      have clinical significance. CLINICAL RELEVANCE: Endoleaks originating from
      retrograde flow in the side branch vessels of the aneurysm generate significant
      levels of intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. At
      least 2 patent side branch vessels appear to be necessary to cause persistent
      patency of type II endoleak in the canine model. Further studies will be
      necessary to enable more complete characterization of retrograde endoleaks and to
      extend these findings to allow clinical application. However, these results
      suggest that persistently patent type II endoleaks are clinical significance and
      may require more intensive follow-up intervention.

PMID- 15557916
TI  - Genetic risk factor characterizes abdominal aortic aneurysm from arterial
      occlusive disease in human beings: CCR5 Delta 32 deletion.
AB  - OBJECTIVE: Inflammation is involved in the pathogenesis of atherosclerosis and
      abdominal aortic aneurysm (AAA), and chemokines are mediators of the inflammatory
      process. The homozygous Delta 32 deletion mutation of the gene of the chemokine
      receptor CCR5 is a cause of its lack in inflammatory cells. The purpose of this
      study was to investigate the relationship between CCR5 Delta 32 deletion mutation
      and AAA, peripheral arterial occlusive disease (PAOD), and carotid stenosis.
      METHODS: The CCR5 Delta 32 polymorphism was genotyped in 380 subjects: 70
      patients operated on to treat AAA (21 ruptured AAAs, 49 elective repair), 76
      patients with PAOD, 62 patients with carotid stenosis, and 172 age-matched and
      sex-matched healthy control subjects. Risk factors for AAA were considered. Each
      patient was assessed according to a diagnostic procedure tailored to symptoms at
      presentation. RESULTS: In patients with AAA the Delta allelic variation was
      significantly different compared with control subjects (P = .002; odds ratio
      [OR], 2.7; 95% confidence interval [CI], 1.41-5.15). The increased presence of
      this allele differentiates AAA from both PAOD (P = .017; OR, 2.77; 95% CI, 1.17
      6.52) and carotid stenosis (P = .01; OR, 3.47; 95% CI, 1.31-9.11). The presence
      in the genotype of patients with AAA of at least 1 Delta 32 allele is more
      frequent in ruptured AAAs than in electively repaired AAAs (genotype: OR, 4.04;
      95% CI, 1.34-12.1; P = .011; allelic frequency: OR, 2.75; 95% CI, 1.07-7.07; P =
      .035). Among the patients, multiple regression analysis showed that the Delta 32
      allele is an independent risk factor for AAA vs PAOD (OR, 3.13; 95% CI, 1.33
      7.33; P = .012) and for ruptured AAAs vs electively repaired AAAs (OR, 3.52; 95%
      CI, 1.01-11.80; P = .045). CONCLUSIONS: CCR5 Delta 32 deletion mutation is
      significantly more frequent in patients with AAA than in control subjects and in
      both patients with PAOD and carotid stenosis, and could be a factor that
      differentiates AAA from PAOD, and ruptured AAAs from AAAs that can be electively
      repaired. CLINICAL RELEVANCE: The major threat of abdominal aortic aneurysm (AAA)
      is rupture, accounting for extremely high mortality. This occurrence has been
      correlated to aneurysm size, but it is a common observation that small AAAs can
      rupture and large AAAs can remain stable for many years. This study was carried
      out in an attempt to search for genetic markers of aneurysm rupture. Some single
      nucleotide polymorphisms are implicated in acceleration of transcription for
      enzymes involved in the inflammatory process and in extracellular matrix
      remodeling. An association between single nucleotide polymorphisms and aneurysm
      rupture could enable better selection for surgical indications in patients with
      small AAs and in patients at poor risk with large AAAs.

PMID- 15557917
TI  - Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular
      contraction.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common disease with as yet
      unclear cause. Increased matrix metalloproteinase (MMP) levels in the plasma and
      aorta are a consistent finding in AAA. Although the role of MMPs in AAA has
      largely been attributed to degradation of the extracellular matrix proteins, the
      effects of MMPs on the mechanisms of aortic contraction are unclear. The purpose
      of this study was to test the hypothesis that MMPs promote aortic dilation by
      inhibiting the Ca2+ mobilization mechanisms of smooth muscle contraction.
      METHODS: Isometric contraction and 45Ca2+ influx were measured in aortic strips
      isolated from male Sprague-Dawley rats treated or not treated with MMP-2 and MMP
      9. RESULTS: In normal Krebs solution (2.5 mmol/L Ca2+ ) phenylephrine (10-5
      mol/L) caused contraction of the aortic strips, which was significantly inhibited
      (P < .05) by MMP-2 (maximum, 48.9% +/- 5.0%) and to a greater extent by MMP-9
      (maximum, 69.8% +/- 6.2%). The MMP-induced inhibition of phenylephrine
      contraction depended on concentration and time. The inhibitory effects of MMPs on
      phenylephrine contraction were reversible. In Ca2+ -free (2 mmol/L ethylene
      glycol bis[beta-aminoethyl ether]-N,N,N',N'-tetraacetic acid) Krebs solution
      phenylephrine caused a small contraction that was not inhibited by MMP-2 or MMP
      9, which suggests that MMPs do not inhibit Ca2+ release from the intracellular
      stores. Membrane depolarization with 96 mmol/L of potassium chloride, which
      stimulates Ca2+ entry from the extracellular space, caused a time-dependent and
      reversible contraction, which was inhibited by MMP-2 and MMP-9. Histologic
      studies of MMP-treated tissues stained with hematoxylin-eosin or Verhoeff stain
      for elastin confirmed the absence of degradation of the extracellular matrix. MMP
      2 and MMP-9 also caused significant inhibition of 45Ca2+ influx induced by
      phenylephrine and potassium chloride. CONCLUSIONS: These data suggest that MMP-2
      and MMP-9 promote aortic dilation by inhibiting the Ca2+ entry mechanism of
      vascular smooth muscle contraction. CLINICAL RELEVANCE: Abdominal aortic aneurysm
      (AAA) is a slow and progressive disease. The late stages of AAA are characterized
      by degenerative changes in the extracellular matrix and smooth muscle components
      of the aortic wall. The present study describes novel inhibitory effects of
      matrix metalloproteinase (MMP) on the Ca2+ entry mechanisms of aortic smooth
      muscle contraction, even in the absence of extracellular matrix degradation. The
      MMP-induced inhibition of aortic contraction may further explain the role of
      increased MMP activity particularly during the early development of AAA. Chronic
      exposure to MMPs may lead to protracted inhibition of aortic contraction,
      progressive aortic dilation, and aneurysm formation. MMP-9 is a more potent
      inhibitor of aortic contraction than MMP-2, consistent with a more dominant role
      in AAA. Restoration and preservation of smooth muscle contractile function by
      specific inhibitors of MMPs may represent a new strategy in preventing the
      progression of small AAA.

PMID- 15557918
TI  - Long-term reduction of medial and intimal thickening in porcine saphenous vein
      grafts with a polyglactin biodegradable external sheath.
AB  - OBJECTIVES: The development of neointimal hyperplasia with subsequent
      atherosclerotic deposition has been proposed to cause most late vein graft
      failures. Our unit has previously demonstrated that placement of a macroporous,
      loose-fitting polyester external stent prevents neointimal thickening in porcine
      vein grafts, and has been proposed as a therapeutic strategy to prevent late vein
      graft failure. To reduce any potential long-term complications of the permanent
      polyester stent, a study was undertaken to investigate the effect of a
      biodegradable external stent on porcine vein graft thickening at 1 month and to
      identify its longer term effects at 6 months. METHODS: Bilateral saphenous vein
      to common carotid artery interposition grafting was performed in Large White pigs
      (25-32 kg; n = 6 per time course group) according to UK Home Office guidelines. A
      commercially constructed loose-fitting 8-mm-diameter polyglactin stent was placed
      externally around the vein graft on one side, and the contralateral side remained
      unstented to serve as control. The external stent was designed to biodegrade and
      hence disappear within 90 days. Grafts were left in situ for 1 month in 1 group
      of animals, and for up to 6 months in the other group, before explantation. Graft
      morphometric features were assessed with computer-aided planimetry. RESULTS: At 1
      month the vein grafts fitted with the polyglactin stent demonstrated a
      statistically significant decrease in neointimal thickening (0.038 mm;
      interquartile range [IQR], 0.035-0.039 mm) compared with the unstented control
      grafts (0.13 mm; IQR; 0.11-0.19; P = .0012), and also in medial thickening (0.09
      mm; IQR, 0.086-0.093) compared with unsheathed control grafts (0.302 mm; IQR,
      0.272-0.414; P = .0012). The 6-month polyglactin stented grafts also demonstrated
      a statistically significant reduction in neointimal thickening (0.049 mm; IQR,
      0.047-0.07; P = .0012) compared with control grafts (0.178 mm; IQR, 0.164-0.19),
      and also in medial thickening (0.105 mm; IQR, 0.095-0.143) compared with
      unstented grafts (0.421 mm; IQR, 0.35-0.44; P = .0012, Mann-Whitney U test).
      CONCLUSION: The loose-fitting biodegradable polyglactin external stent reduces
      porcine vein graft thickening at 1 month, which persists in the long term, even
      after degradation of the stent itself. This effective removal of the stent may
      therefore reduce the long-term risks for infection and mechanical complications
      associated with implanted prosthetic material while still eliciting the primary
      objective of preventing graft thickening over the long term. Biodegradable
      external stents therefore have potential advantages over permanent stent material
      in clinical application. CLINICAL RELEVANCE: Arteriovenous bypass graft failure
      has a huge economic effect on health care resources, and a devastating effect o
      the patient. The attenuation of vein wall thickening, with subsequent luminal
      narrowing and occlusion, is a major goal in improving the longevity of the venous
      graft, to reduce secondary percutaneous and surgical interventions. The
      biodegradable external stent demonstrated in this study has possible clinical
      applications in bypass procedures with autogenous venous tissue, and represents a
      novel approach to ameliorating the problem of intimal hyperplasia that plagues
      these grafts.

PMID- 15557919
TI  - Endoluminal repair of carotid artery pseudoaneurysms: a word of caution.
AB  - This report describes our results with covered endoluminal stents in the
      management of 4 patients with carotid artery pseudoaneurysms (PSAs) following
      carotid endarterectomy (CEA). Two patients had symptomatic embolization of
      thrombus from the PSA's into branches of the middle cerebral arteries (MCA)
      during deployment of the stents. Endoluminal stents were deployed uneventfully in
      the other two. At 12 month follow-up, one patient had an occlusion of the stent.
      While endoluminal therapy of carotid PSAs in an effective method to exclude PSAs,
      embolization of thrombus is a potential hazard. The long-term patency of covered
      stents in the carotid artery is unknown.

PMID- 15557920
TI  - Endovascular repair of an infected carotid artery pseudoaneurysm.
AB  - Pseudoaneurysm formation after carotid endarterectomy is a rare but potentially
      lethal complication. The risks for embolization and continued expansion
      necessitate repair. Traditional surgical repair of carotid pseudoaneurysms is
      often technically demanding, and is associated with relatively high morbidity and
      mortality. Endovascular stent grafts have been used to treat both posttraumatic
      and postoperative carotid pseudoaneurysms. An endovascular approach to these
      pseudoaneurysms limits the risks for operative damage to surrounding structures
      and the potential for substantial blood loss. We present the case of an infected
      carotid pseudoaneurysm that was successfully treated with a covered stent graft.

PMID- 15557921
TI  - Primary stenting of bilateral radiation-induced external iliac stenoses.
AB  - Radiation-induced arteritis is a described rare complication of radiotherapy,
      particularly in patients with cancer. We report bilateral radiation-induced
      arteritis leading to stenoses in the external iliac arteries, which was treated
      with primary percutaneous arterial stenting, and review the current literature on
      the topic.

PMID- 15557923
TI  - Spontaneous dissection and rupture of common iliac artery in a patient with
      fibromuscular dysplasia: a case report and review of the literature on iliac
      artery dissections secondary to fibromuscular dysplasia.
AB  - Spontaneous dissection and rupture of the iliac artery is an unusual finding in
      patients with fibromuscular dysplasia (FMD). We report the case of a patient with
      FMD who required emergent surgery because of rupture of an iliac artery
      dissection, and review 9 previously reported cases of iliac artery dissection
      associated with FMD. A 30-year-old man had abdominal pain, and went into shock.
      Angiograms revealed dissection of the left common iliac artery with
      extravasation. At emergent surgery the rupture site was in the proximal left
      common iliac artery and extended to the left external iliac artery. Interposition
      of the diseased artery with a Dacron graft was attempted, but cardiac arrest
      occurred, and resuscitation was unsuccessful. Pathologic examination showed
      typical characteristics of diffuse medial FMD. Ten cases (5 male and 5 female
      patients), including the present case, with dissection of iliac arteries
      associated with FMD have been reported. Median patient age was 45 years (range,
      29-56 years). Three of the 10 patients had acute onset of symptoms, and the
      remainder had gradual development of intermittent claudication or groin pain.
      Only the present case had evidence of rupture. The site of dissection was in the
      external iliac artery in 8 patients and the common iliac artery in 2 patients.
      Anatomic bypass or interposition of the diseased artery was performed in 8
      patients; the others received conservative treatment. There was no mortality in
      the 9 previously reported cases. Fatal acute dissection and rupture of the common
      iliac artery occurred in a patient with FMD, even though the clinical course of
      this disease is relatively benign. FMD should be considered the cause of
      dissection and rupture of the iliac artery in a patient with symptoms but of non
      atherosclerotic age.

PMID- 15557925
TI  - Late lumbar hemorrhage after open repair of abdominal aortic aneurysm: computed
      tomographic appearance resembling type II endoleak.
AB  - Development of endoleak after conventional open repair of abdominal aortic
      aneurysm is less well documented compared with endovascular stenting. We present
      a case report of a 65-year-old man who had sudden onset of back pain with central
      abdominal tenderness 34 days after successful open repair of an abdominal aortic
      aneurysm. Urgent laparotomy revealed the presence of a noninfective intrasac
      hemorrhage, due to recanalization of the lumbar arteries. These were successfully
      suture ligated. Delayed lumbar hemorrhage should be an important differential
      diagnosis by frontline medical personnel in patients with recent open aneurysm
      repair. The recent literature on other causes and management strategies is also
      reviewed.

PMID- 15557926
TI  - Common celiacomesenteric trunk: aneurysmal and occlusive disease.
AB  - Eighteen patients (14 men, 4 women), ages 24 to 77 years, with a common
      celiacomesenteric trunk (CMT) were treated between 1965 and 2004 at the
      University of Michigan. Four patients had CMT aneurysmal or occlusive disease
      that led to operative treatment. Pertinent arteriographic findings in these 4
      patients included a CMT aneurysm (n = 2), an occluded proximal CMT (n = 1), and a
      type III aortic dissection that was compressing the CMT (n = 1). Therapy in these
      4 patients included placement of a polytetrafluoroethylene bypass graft from the
      supraceliac aorta to the CMT (n = 2) or a Dacron bypass graft from a
      thoracoabdominal bypass to the CMT (n = 1), and endovascular fenestration of the
      septum between the true and false lumens of an aortic dissection at the level of
      the CMT (n = 1).

PMID- 15557927
TI  - Dorsalis pedis artery true aneurysm due to atherosclerosis: case report and
      literature review.
AB  - We describe a dorsalis pedis artery true aneurysm due to atherosclerosis. A 61
      year-old woman had a pulsatile and painful tumor on the right dorsal part of the
      foot, and magnetic resonance imaging revealed an aneurysm of the dorsalis pedis
      artery. Resection of the aneurysm was completed without complications. Pathologic
      analysis showed true aneurysm due to atherosclerosis. We review the literature on
      true aneurysm of the infrapopliteal arteries, including the dorsalis pedis
      artery, and discuss the clinical presentation and surgical management.

PMID- 15557928
TI  - Transcatheter embolization of a splenic artery aneurysm.

PMID- 15557929
TI  - Canine or chameleon (revisited): a never-ending challenge in a perpetually
      changing world.

PMID- 15557930
TI  - Ethics of refusal to treat patients as a social statement.

PMID- 15557931
TI  - Regarding "Floating thoracic aortic thrombus in 'protein S' deficient patient".

PMID- 15557933
TI  - Regarding "Aortofemoral bypass in young patients with premature atherosclerosis:
      is superficial femoral vein superior to Dacron?".

PMID- 15557934
TI  - Regarding "A new approach to carotid angioplasty and stenting with transcervial
      occlusion and protective shunting: why it may be a better carotid artery
      intervention".

PMID- 15557936
TI  - Regarding "Decreased use of iliac extensions and reduced graft junctions with
      software assisted centerline measurements".

PMID- 15557941
TI  - A prospective comparison of the yield of EUS in primary vs. recurrent idiopathic
      acute pancreatitis.
AB  - BACKGROUND: It is uncertain whether EUS should be performed after a single
      episode of idiopathic pancreatitis vs. recurrent episodes or if clinical factors
      can predict positive EUS findings. METHODS: Consecutive patients with a single
      episode of idiopathic pancreatitis or with recurrent episodes underwent EUS (with
      analysis of bile for bilirubinate and cholesterol crystals, when possible). The
      diagnostic yield was compared for patients with a single episode of idiopathic
      pancreatitis and recurrent episodes (stratified by cholecystectomy status).
      Predictors of positive EUS findings were sought. EUS was considered "positive" if
      it identified any possible cause of pancreatitis other than chronic pancreatitis.
      RESULTS: A total of 370 patients were studied (246 no-cholecystectomy group [134
      single episode of idiopathic pancreatitis, 112 recurrent episodes] and 124 post
      cholecystectomy group [67 single episode of idiopathic pancreatitis, 57 recurrent
      episodes]). Overall, EUS yielded a positive finding in 29.2%. For patients in the
      no-cholecystectomy group, positive EUS findings were not significantly more
      frequent in those with a single episode of idiopathic pancreatitis vs. those with
      recurrent episodes (31.3% vs. 32.1%; p = 0.89). In the post-cholecystectomy
      group, the yield was not significantly different for single episode of idiopathic
      pancreatitis (29.9%) vs. recurrent episodes (17.5%) ( p = 0.15). Chronic
      pancreatitis was the only abnormality identified in 30.9% of patients in the no
      cholecystectomy group vs. 26.6% of those in the post-cholecystectomy group ( p =
      0.24). It was the most common abnormality found in all 4 subgroups (range 16.4%
      42.0%) and was approximately twice as frequent in patients with recurrent
      episodes vs. a single episode of idiopathic pancreatitis (no-cholecystectomy:
      42.0% vs. 21.6%, p = 0.0008; post-cholecystectomy: 38.6% vs. 16.4%, p = 0.008).
      Analysis of bile revealed crystals in 38/80 (47.5%) patients in whom it could be
      performed. Patients with positive EUS findings tended to be older. CONCLUSIONS:
      In patients with idiopathic pancreatitis, the yield of EUS is not significantly
      different after an initial attack or after recurrent attacks. Therefore, it is
      reasonable to perform EUS after an initial attack of idiopathic acute
      pancreatitis, especially in older patients.

PMID- 15557942
TI  - Cardiovascular complications after GI endoscopy: occurrence and risks in a large
      hospital system.
AB  - BACKGROUND: There is limited information concerning the risks for, and occurrence
      of, cardiovascular complications because of GI endoscopy. Published data are
      based on questionnaire surveys, which have a potential for bias. Moreover,
      available studies pertain exclusively to out-patients. METHODS: In-patients and
      day-stay patients who incurred charges for endoscopy with endoscopic procedure
      coding from 1999 through 2001 were identified from a financial database for all 9
      hospitals in a large health care system. From these patients, those considered
      "at risk" for cardiovascular complications were selected based on charges for
      cardioactive medications, cardiac enzyme determinations, or intensive care
      services on the day of or the day after endoscopy. Medical records were reviewed
      for 25% of these patients, selected at random, noting demographics, history, and
      a modified Goldman score in patients with cardiovascular complications (defined
      as arrhythmia, chest pain or anginal equivalent, hypotension or myocardial
      infarction occurring within 24 hours after endoscopy). Identical information was
      obtained from a random sample of 0.5% of the chart records for all patients
      undergoing endoscopy. RESULTS: Patients who underwent endoscopy were not reliably
      identified for one hospital. This hospital was omitted from the calculation of
      the extrapolated rate of complication occurrence, but patients identified through
      chart review as having or not having a complication after endoscopy were included
      in the risk analysis. The extrapolated rate of occurrence of cardiovascular
      complications was 308: 95% CI [197, 457] per 100,000 procedures. Independent risk
      factors were: male gender, modified Goldman score, and use of propofol.
      CONCLUSIONS: In this study of patients undergoing hospital-based GI endoscopy,
      the risk of procedure-related cardiovascular complications was 2 to 70 times
      higher than previously reported. This finding may be ascribed to differences in
      the populations sampled and to a case-finding method that minimized reporting and
      ascertainment biases.

PMID- 15557943
TI  - Is routine sedation or topical pharyngeal anesthesia beneficial during upper
      endoscopy?
AB  - BACKGROUND: Upper endoscopy is an invasive procedure. However, the benefits of
      routinely administered sedative medication or topical pharyngeal anesthesic are
      controversial. The aim of this study was to clarify their effects on patient
      tolerance and difficulty of upper endoscopy. METHODS: A total of 252 patients
      scheduled for diagnostic upper endoscopy were randomly assigned to 4 groups: (1)
      sedation with midazolam and placebo pharyngeal spray (midazolam group), (2)
      placebo sedation and lidocaine pharyngeal spray (lidocaine group), (3) placebo
      sedation and placebo pharyngeal spray (placebo group), and (4) no intravenous
      cannula/pharyngeal spray (control group). The endoscopist and the patient
      assessed the procedure immediately after the examination. Another questionnaire
      was sent to the patients 2 weeks later. RESULTS: Patients in the midazolam group
      rated the examination easier and less uncomfortable compared with those in the
      other groups. The differences were especially evident in the questionnaires
      completed 2 weeks after the examination ( p < 0.001). Lidocaine did not
      significantly improve patient tolerance. However, endoscopists found the
      procedure easier in patients in the lidocaine group compared with the midazolam (
      p < 0.01) and control groups ( p < 0.01) but not the placebo group. CONCLUSIONS:
      Routine administration of midazolam for sedation increased patient tolerance for
      upper endoscopy. However, endoscopists found intubation to be more difficult in
      sedated vs. non-sedated patients. Topical pharyngeal anesthesia did not enhance
      patient tolerance, but it did make upper endoscopy technically easier compared
      with endoscopy in patients sedated with midazolam without topical pharyngeal
      anesthesia, and in patients who had no sedation or pharyngeal anesthesia, but not
      in patients who received placebo sedation and placebo pharyngeal anesthesia.

PMID- 15557944
TI  - Esophageal stents with antireflux valve for tumors of the distal esophagus and
      gastric cardia: a randomized trial.
AB  - BACKGROUND: Self-expandable metal stents deployed across the gastroesophageal
      junction predispose to gastroesophageal reflux. The efficacy of a stent with an
      antireflux mechanism in preventing gastroesophageal reflux was assessed. METHODS:
      Thirty patients with carcinoma of the distal esophagus or of the gastric cardia
      were randomized to receive either a stent with a windsock-type antireflux valve
      (FerX-Ella) (n = 15) or a standard open stent (n = 15) of the same design minus
      the valve. Gastroesophageal reflux was assessed by using standardized
      questionnaires and by 24-hour pH monitoring 14 days after treatment. RESULTS:
      Technical problems occurred during stent placement in 3 patients: migration (n =
      2) and a problem with the introducing system (n = 1). Dysphagia improved from a
      median score of 3 (liquids only) to 1 (eat some solid food) in the antireflux
      group and from 3 to 0 (solid foods) in the open stent group ( p > 0.20). Reflux
      symptoms were reported by 3/12 patients (25%) with an antireflux stent and by
      2/14 (14%) with an open stent. In 11 patients, 24-hour pH monitoring was
      obtained, and increased esophageal acid exposure (normal: <4%) was present with
      both types of stent: median 24-hour reflux time (9 patients) with the antireflux
      stent was 23% vs. 10% in (2 patients) with the open stent ( p = NS). Major
      complications occurred in 3 patients (20%) in each group and included bleeding (n
      = 3), severe pain (n = 2), and aspiration pneumonia (n = 1). The main cause of
      recurrent dysphagia was stent migration, which occurred in 7 of the 30 patients
      (23%). CONCLUSIONS: The FerX-Ella antireflux stent provided relief of dysphagia
      caused by malignancy of the distal esophagus and gastric cardia. However, the
      antireflux valve failed to prevent gastroesophageal reflux.

PMID- 15557945
TI  - Prediction of appropriateness of local endoscopic treatment for high-grade
      dysplasia and early adenocarcinoma by EUS and histopathologic features.
AB  - BACKGROUND: Endoscopic techniques are being developed for the local treatment of
      early stage esophageal cancer. However, such therapy is not appropriate for
      patients with lymph node metastasis. The aim of this study was to analyze the
      histopathologic features of high-grade dysplasia and early stage adenocarcinoma
      and to relate these to lymph node involvement. METHODS: Pathology reports were
      reviewed for all 367 patients who underwent subtotal esophagectomy for high-grade
      dysplasia or adenocarcinoma of the esophagus or the gastroesophageal junction
      between January 1993 and December 2001. Patients with histopathologically
      confirmed high-grade dysplasia or T1 carcinoma were included (n = 77). Pre
      operative EUS results were assessed. All lesions were histopathologically
      subdivided in 6 different stages (mucosal 1-3 and submucosal 1-3). RESULTS: EUS
      staged 61 patients as N0. EUS correctly predicted the absence of positive lymph
      nodes in 57 (93%) of these patients. Histopathologically, m1, m2, m3, and sm1
      cancers never had lymph node metastases, whereas 3 of 13 sm2 tumors (23%) and 9
      of 13 sm3 tumors (69%) had lymph node involvement. Lymphangio invasion was
      present exclusively in sm2 and sm3 cancers. Factors that predicted the presence
      of lymph node metastasis were the following: tumor diameter greater than 3 cm,
      infiltration of malignancy beyond sm1, poor differentiation grade, and lymphangio
      invasion, although only infiltration beyond sm1 remained significant in the
      definitive multivariate analysis. CONCLUSIONS: EUS and the histopathologic
      features of high-grade dysplasia and early stage adenocarcinoma of the esophagus
      or the gastroesophageal junction can predict the presence of lymph node
      involvement. These data can be used to identify patients for whom local
      endoscopic treatment may be appropriate.

PMID- 15557946
TI  - Second capsule endoscopy for patients with severe iron deficiency anemia.
AB  - BACKGROUND: Patients with iron deficiency anemia are subjected to multiple
      endoscopic and radiologic examinations of the GI tract. If negative, some of the
      examinations are repeated, occasionally with positive findings. The diagnostic
      yield of a second capsule endoscopy in such patients is unknown. The aim of the
      current study was to assess the diagnostic yield of a second capsule endoscopy in
      patients with significant iron deficiency anemia and a previous negative
      evaluation. METHODS: Twenty patients with iron deficiency anemia (Hb < 10 g/dL)
      were enrolled. All had at least one normal evaluation of the GI tract, including
      capsule endoscopy. A second capsule endoscopy examination was offered to all
      patients. RESULTS: The time between the first and the second capsule endoscopy
      ranged from 2 months to 1 year. Depending on the nature of an abnormality and its
      relevance to blood loss, the findings were classified as positive, suspicious,
      clinically irrelevant, or negative. In 7 patients, the second capsule endoscopy
      disclosed findings that were classified as either positive or suspicious
      findings, including arteriovenous malformations (2), flat polypoid lesion (1),
      edematous inflamed mucosa (1), erosions (1), and hemorrhagic gastritis (1).
      Lesions were located in the small intestine (5), the stomach (1), and the cecum
      (1). Based on the findings of the second capsule endoscopy, therapy was changed
      in two patients (10%). CONCLUSIONS: A second capsule endoscopy should be
      considered for patients with severe iron deficiency anemia and negative initial
      evaluation.

PMID- 15557947
TI  - The characteristics and the prognosis for patients presenting with actively
      bleeding esophageal varices at endoscopy.
AB  - BACKGROUND: It remains unresolved whether the prognosis is worse for patients who
      present with actively bleeding varices at endoscopy compared with those in whom
      variceal bleeding has stopped. METHODS: Patients with acute esophageal variceal
      bleeding were enrolled in this study and were divided into two groups: an active
      bleeding group and an inactive bleeding group. All patients had band ligation
      shortly after endoscopic examination and underwent elective ligation procedures
      until the varices were obliterated. Patients were followed for 1 year or until
      death. Short- and long-term prognoses were compared. RESULTS: The active bleeding
      group included 54 patients and the inactive bleeding included 251 patients.
      Initial hemostasis was achieved in 93% in the active group and 99% in the
      inactive group ( p = not significant). The rate of recurrent variceal bleeding
      within 30 days was 24% in the active bleeding group vs. 12% in the inactive
      bleeding group ( p = 0.01); the mortality rates were 18% and 8%, respectively ( p
      = 0.03 in a single statistical test; however, Bonferroni correction for the
      multiple testing of data removed this significance). The rate of recurrent
      variceal bleeding within 1 year was 37% in the active bleeding group and 27% in
      the inactive bleeding group ( p = 0.06); the mortality rates were 22% and 21%,
      respectively ( p = not significant). CONCLUSIONS: Whether variceal bleeding is
      active or inactive at endoscopy, variceal ligation is equally effective for
      control of bleeding. The rates of recurrent bleeding and mortality at 1 month
      were significantly higher among patients with active bleeding. However, the
      mortality rate was similar for both groups at 1 year.

PMID- 15557948
TI  - Complications of ERCP: a prospective study.
AB  - BACKGROUND: Studies of ERCP-related morbidity seldom include a sufficient patient
      follow-up. The aim of this study was to characterize and to evaluate the
      frequency of complications, cardiopulmonary untoward events in particular.
      METHODS: All patients undergoing ERCP during a 2-year period were included in
      this prospective study. Complications were assessed at the time of ERCP and by
      postal/telephone contact at 30-days after the procedure. RESULTS: A total of 1177
      ERCPs were included in the analysis, of which 56.2% were therapeutic. The 30-day
      complication rate was 15.9%; the procedure-related mortality rate was 1.0%. Post
      ERCP pancreatitis occurred in 3.8% of patients (3 deaths). Hemorrhage or
      perforation occurred with 0.9% and 1.1%, respectively, of the procedures (3
      deaths). One perforation that resulted in the death of the patient occurred after
      placement of an endoprosthesis. Cholangitis occurred in relation to 5% of the
      ERCP procedures (3 deaths). Cardiorespiratory complications occurred in 2.3% (2
      deaths). Dilated bile duct ( p = 0.0001), placement of stent ( p = 0.001), and
      use of more than 40 mg of hyoscine-N-butyl bromide ( p < 0.05) were risk factors
      for complications by multivariate analysis. Risk of pancreatitis was increased
      with age under 40 years ( p = 0.0078), placement of stent ( p = 0.031), and a
      dilated bile duct ( p = 0.036). CONCLUSIONS: This prospective study confirms that
      the complication rate of ERCP including therapeutic procedures is high.
      Cardiopulmonary complications were not as common as expected, despite being the
      special focus of the study.

PMID- 15557949
TI  - Direct visualization of intestinal villi by high-resolution magnifying upper
      endoscopy: a validation study.
AB  - BACKGROUND: New generation videoendoscopes potentially may visualize duodenal
      villi. This study compared endoscopic findings with this type of instrument to
      the histopathologic evaluation of duodenal villi. METHODS: A total of 191
      patients underwent upper endoscopy for the purpose of obtaining duodenal biopsy
      specimens. The findings were assessed independently by 3 experienced observers by
      using a commercially available, high-resolution, high-magnifying (x2)
      videoendoscope. The duodenal villous profile was determined by endoscopic
      magnification and by endoscopic magnification after filling the duodenum with
      water. With both endoscopic magnification and endoscopic magnification after
      filling the duodenum with water, villous patterns were scored as the following:
      definitely present, partially present, or definitely absent. Villous patterns
      also were histopathologically scored as the following: normal, partial villous
      pattern, or total villous atrophy. RESULTS: Interobserver variability was
      excellent (kappa = 0.93). The concordance between either endoscopic magnification
      or endoscopic magnification after filling the duodenum with water and histology
      was 100% for presence/absence of villi. The sensitivity, the specificity, and the
      positive and negative predictive values of endoscopic magnification for detection
      of any villous abnormality were 95%, 99%, 95%, and 99%, respectively; the
      respective values of endoscopic magnification after filling the duodenum with
      water were 95%, 98%, 92%, and 99%. CONCLUSIONS: High-resolution magnifying upper
      endoscopy can reliably predict the presence or the absence of duodenal villi.

PMID- 15557950
TI  - Cost-effectiveness of photodynamic therapy for high-grade dysplasia in Barrett's
      esophagus.
AB  - BACKGROUND: Photodynamic therapy appears to be effective in ablating high-grade
      dysplasia in Barrett's esophagus. Our aim was to identify the most effective and
      cost-effective strategy for managing high-grade dysplasia in Barrett's esophagus
      without associated endoscopically visible abnormalities. METHODS: By using
      decision analysis, the lifetime costs and benefits of 4 strategies for which long
      term data exist were estimated by us: esophagectomy, endoscopic surveillance,
      photodynamic therapy, followed by esophagectomy for residual high-grade
      dysplasia; and photodynamic therapy followed by endoscopic surveillance for
      residual high-grade dysplasia. It was assumed by us that there was a 30%
      prevalence of cancer in high-grade dysplasia patients and a 77% efficacy of
      photodynamic therapy for high-grade dysplasia and early cancer. RESULTS:
      Esophagectomy cost 24,045 dollars, with life expectancy of 11.82 quality-adjusted
      life years. In comparison, photodynamic therapy followed by surveillance for
      residual high-grade dysplasia was the most effective strategy, with a quality
      adjusted life expectancy of 12.31 quality-adjusted life years, but it also
      incurred the greatest lifetime cost (47,310 dollars) for an incremental cost
      effectiveness of 47,410 dollars/quality-adjusted life years. The results were
      sensitive to post-surgical quality of life and survival, and to cancer prevalence
      if photodynamic therapy efficacy for cancer was less than 50%. CONCLUSIONS:
      Photodynamic therapy followed by endoscopic surveillance for residual high-grade
      dysplasia appears to be cost effective compared with esophagectomy for patients
      diagnosed with high-grade dysplasia in Barrett's esophagus. Clinical trials
      directly comparing these strategies are warranted.

PMID- 15557951
TI  - Endoscopic snare papillectomy for tumors of the duodenal papillae.
AB  - BACKGROUND: Tumors of the major and the minor duodenal papillae can be malignant
      or premalignant, and traditionally are treated by surgical excision. This study
      evaluated the safety and the outcome of endoscopic snare resection of such
      tumors. METHODS: All patients with tumors of the major or the minor papilla
      treated by endoscopic snare resection over a 10-year period (1994-2003) were
      identified from an ERCP database. Patients with tumors that had endoscopic
      features of malignancy and those proven to be cancerous by biopsy were excluded.
      Papillectomy was performed by electrosurgical snare resection. A pancreatic stent
      usually was placed before or after excision. Residual tumor was eradicated by
      repeated procedures. Endoscopic surveillance was at the discretion of the
      endoscopist. RESULTS: Seventy snare resections were performed in 55 patients
      (mean age 59 years). Histopathologic diagnoses were the following: adenoma (45
      patients; 7 with focal high-grade dysplasia, 6 with intraductal extension),
      adenocarcinoma (5), carcinoid tumor (2), gastric heterotopia (1), and normal
      histology (2). Fourteen patients had familial adenomatous polyposis. Of the 39
      patients with isolated extraductal adenoma per cholangiogram, two underwent
      surgical resection because of persistent high-grade dysplasia, and 37 were
      successfully treated by endoscopic papillectomy alone. During follow-up (mean 30
      months), 18 of 37 patients (49%) had no recurrence, 7 had recurrent adenoma (mean
      time interval to recurrence 27 months), two died of unrelated illnesses, and 10
      are awaiting follow-up. Of the 6 patients with intraductal adenoma per
      cholangiogram, two underwent surgical resection, two had intraductal photodynamic
      therapy, and two had endoscopic snare resection. Intraductal tumor in the 4
      latter patients was eliminated, although it recurred in one of the patients who
      had photodynamic therapy. Of the 7 patients with adenocarcinoma or carcinoid
      tumor, pancreaticoduodenectomy was performed in 3 and palliative papillectomy was
      performed in 4 unsuitable for surgery. One patient with carcinoid tumor of the
      minor papilla is alive, without recurrence, at 5 years after papillectomy. There
      were 10 procedure-related complications (14.5%), including pancreatitis (5),
      bleeding (4), and mild perforation (1). There was no procedure-related death.
      CONCLUSIONS: Most adenomas of the duodenal papillae without intraductal extension
      can be fully resected by snare papillectomy. However, adenoma recurs in about a
      third of patients. Endoscopic therapy appears to be a reasonable alternative to
      surgery for management of papillary tumors. Longer follow-up is needed to
      determine the true recurrence rate and if endoscopic re-treatments are effective.

PMID- 15557952
TI  - An international survey of the clinical practice of EUS.
AB  - BACKGROUND: No comparative information exists regarding clinical variations in
      EUS practice patterns among American and international endosonographers. METHODS:
      Eligible attendees of the XIIIth International Symposium on EUS, October 4-6
      2002, New York, New York, were asked to complete a 2-page survey questionnaire on
      clinical practice of EUS. RESULTS: A total of 191 of 391 eligible attendees
      (48.9%) participated in the survey (110 from the United States, 81 from 30
      different countries). The mean age of participants was 40.5 (10.6) years, and 171
      (89.5%) were men. A total of 102 endosonographers (53.4%) were in academic
      practice. The majority (150, 78.5%) also performed ERCP. Seventy-eight (40.8%)
      had performed EUS for more than 5 years and 21 (11%) for less than 1 year. Only
      36 (18.8%) had more than 6 months of dedicated hands-on EUS training, and more
      than a third of the respondents learned to perform EUS by observing others or
      they were self-taught. Compared with respondents from the United States,
      relatively fewer international respondents were performing open-access EUS,
      pancreatobiliary EUS procedures, and interventions such as EUS-guided FNA and
      celiac plexus neuralysis. CONCLUSIONS: This survey provides insight into the
      status of EUS as practiced in the United States and internationally. Although it
      appears that over the last decade EUS has become disseminated fairly uniformly on
      a global basis, a lack of consistent training standards and also inadequate
      opportunities for EUS training remain important areas of concern.

PMID- 15557953
TI  - Clinical impact of strip biopsy for early gastric cancer.
AB  - BACKGROUND: The impact of EMR (strip biopsy method) on the selection of
      subsequent treatment for early gastric cancer was analyzed retrospectively.
      METHODS: A total of 163 consecutive patients with gastric epithelial tumors (186
      lesions) underwent strip biopsy. On the basis of pretherapeutic findings, the
      indications for strip biopsy were classified into 4 groups: benign-malignant
      borderline group (93 lesions), curative indication group (65), diagnostic
      indication group (22), and palliative indication group (6). The clinical impact
      of the strip biopsy result on the subsequent treatment strategy was assessed.
      RESULTS: Of the lesions in the benign-malignant borderline group, 36.6% were
      intramucosal cancer. In the curative indication group, the results of strip
      biopsy differed from the pretherapeutic findings for 7.7% of the lesions. Strip
      biopsy was effective treatment for all lesions in the benign-malignant borderline
      group and for 92.3% of those in the curative indication group. Strip biopsy
      avoided unnecessary surgery in 50% of patients in the diagnostic indication group
      and 16.7% of those in the palliative indication group. After the strip biopsy
      results were explained, 50% of the patients in the palliative indication group
      reversed their initial decision and opted for surgery. Strip biopsy results
      reversed the decision for surgery, which had been based on inaccurate
      pretherapeutic information, in 20% of cases of early gastric cancer. CONCLUSIONS:
      Strip biopsy has a major clinical impact, because it provides an accurate
      diagnosis, aids in the selection of an appropriate treatment strategy, and
      reduces unnecessary surgery.

PMID- 15557954
TI  - Ileal varices and portal hypertensive ileopathy in patients with cirrhosis and
      portal hypertension.
AB  - BACKGROUND: The endoscopic appearance of portal hypertensive intestinal
      vasculopathy is well described in the stomach, the jejunum, and the colon, but
      there is no description of changes that occur in the ileum. METHODS: The terminal
      ileum was intubated at colonoscopy in 44 patients with cirrhosis and portal
      hypertension and 46 control patients. Changes in the terminal ileum were noted.
      In addition, anorectal varices and colopathy were carefully noted and recorded.
      RESULTS: Ileal varices and/or portal hypertensive ileopathy were present in 16 of
      44 (36%) patients with cirrhosis and portal hypertension but not in any control
      patient ( p < 0.01). Ileal varices were present in 8 patients (18%) with
      cirrhosis/portal hypertension and none of the control patients ( p < 0.05).
      Portal hypertensive ileopathy was noted in 11 patients (25%) with cirrhosis and
      portal hypertension and in none of the control patients ( p < 0.05). Ileal
      varices had no association with any other parameter studied. However, ileopathy
      was observed in 9 of the 23 patients with colopathy and in only two of the 21
      patients without colopathy ( p < 0.05). CONCLUSIONS: Ileal varices and mucosal
      changes of portal hypertensive ileopathy occur in patients with cirrhosis and
      portal hypertension. In the population studied, ileopathy was significantly more
      common in patients who had portal hypertensive colopathy.

PMID- 15557955
TI  - Acupuncture for GI endoscopy: a systematic review.

PMID- 15557956
TI  - Defining complications of GI endoscopy: past, present, and future.

PMID- 15557957
TI  - Recommendations for the prevention of transmission of SARS during GI endoscopy.

PMID- 15557958
TI  - Rectal Dieulafoy's lesion.

PMID- 15557959
TI  - Bleeding cecal diverticulum.

PMID- 15557960
TI  - Esophageal submucosal gland duct adenoma.

PMID- 15557961
TI  - Diffuse colonic hemangiomatosis.

PMID- 15557962
TI  - Whipple's disease.

PMID- 15557963
TI  - Protein-losing enteropathy.

PMID- 15557964
TI  - Gastric inflammatory fibroid polyp.

PMID- 15557965
TI  - Clostridial aortitis and colon cancer.

PMID- 15557966
TI  - Endoscopic Doppler US probe for acute peptic ulcer hemorrhage.

PMID- 15557967
TI  - Treatment of recurrent malignant obstruction with a flexible covered metal stent
      after gastric surgery.
AB  - BACKGROUND: The management of gastric outlet obstruction with expandable metallic
      stents is difficult and frequently is associated with late complications. A new,
      flexible, covered metal stent has been developed, which may be suitable for
      treatment of patients with recurrent malignant strictures after gastric surgery.
      METHODS: The stainless-steel stent is covered by a polyethylene membrane. It has
      a proximal funnel attached to an expanded antimigratory segment 29 mm in
      diameter. The flexible covering membrane connects isolated distal segments that
      are 20 mm in diameter. The stent is preloaded in a 6.7-mm-diameter introducer
      system. The structural features and the increased flexibility of this new
      prosthesis are intended to reduce the risk of migration and the frequency of late
      complications, and to broaden the range of applications. RESULTS: This stent was
      used to successfully treat two patients with recurrent tortuous malignant
      strictures after partial or complete gastrectomy. CONCLUSIONS: This new flexible,
      polyethylene-covered stent potentially is a new alternative for the palliation of
      patients with recurrent, inoperable gastric malignant strictures.

PMID- 15557968
TI  - Endoscopic placement of the capsule endoscope in children.
AB  - BACKGROUND: Capsule endoscopy provides a minimally invasive examination of the
      entire small bowel. However, some children and disabled adults may be unable to
      independently ingest the capsule. A new method for endoscopic placement of the
      capsule endoscope is described. METHODS: Consecutive children who required
      capsule endoscopy of the small bowel and who were unable to independently ingest
      the capsule were selected for endoscopic placement. A net retrieval catheter and
      a translucent ligation adaptor were used to hold and stabilize alignment of the
      capsule during endoscopic insertion into the distal duodenum. RESULTS: Eleven
      pediatric patients underwent successful endoscopic placement of a capsule
      endoscope in the duodenum without complication. One capsule migrated back into
      the stomach, where it remained for the life of the battery. CONCLUSIONS:
      Endoscopic placement of the capsule endoscope by using the described technique
      appears to be effective and safe. It facilitates capsule endoscopy in patients
      who are unable to independently ingest the capsule.

PMID- 15557969
TI  - Frequency and clinical outcome of capsule retention during capsule endoscopy for
      GI bleeding of obscure origin.
AB  - BACKGROUND: Capsule endoscopy is now commonly performed for GI bleeding of
      obscure origin. Regional transit abnormality refers to slowed capsule movement
      during capsule endoscopy. The frequency and clinical outcome of capsule retention
      and regional transit abnormalities are unknown. METHODS: Initial capsule
      endoscopies performed at a single institution in 52 patients with GI bleeding of
      obscure origin were reviewed retrospectively. For patients with capsule retention
      or regional transit abnormality, preprocedural characteristics, and post
      procedural outcomes were recorded. OBSERVATIONS: Capsule retention occurred in 7
      patients, all of whom remained asymptomatic. Regional transit abnormality was
      noted in 3 patients. Sources of bleeding were localized in all cases. Seven
      patients underwent surgery. Stricture induced by non-steroidal anti-inflammatory
      drugs was the major cause of retention. In all patients, anemia resolved during
      follow-up. CONCLUSIONS: Capsule retention and regional transit abnormality
      occurred in almost 20% of patients who had capsule endoscopy for GI bleeding of
      obscure origin. These capsule movement abnormalities led to the diagnosis of
      bleeding sources and thereby influenced patient management. A history of non
      steroidal anti-inflammatory drugs use may be associated with an increased risk of
      capsule retention.

PMID- 15557970
TI  - Prediction of bleeding and stricture formation after corrosive ingestion by EUS
      concurrent with upper endoscopy.
AB  - BACKGROUND: Upper endoscopy provides information that can be used to predict
      complications and to facilitate clinical decisions for patients who have ingested
      corrosive substances. The role of EUS in corrosive injury has not been
      investigated. The aim of this study was to determine whether concurrent catheter
      probe EUS provides additional information that predicts complications after
      corrosive injury. METHODS: Eighteen patients were referred (from 1997 to 2003)
      for EGD and concurrent EUS within 24 hours after ingestion of a caustic agent.
      Two patients were excluded (1 pneumoperitoneum, 1 markedly swollen cricoarytenoid
      cartilage/epiglottis). The severity of injury in the different segments of the
      esophagus and stomach was graded (0, 1, 2a, 2b, 3a, 3b) by endoscopy and by EUS
      (0, M, SM, MP, SS). The development of complications during hospitalization and 3
      month follow-up were recorded. OBSERVATIONS: All 16 patients underwent EGD with
      EUS without complication. The frequency of early and late complications increased
      as the endoscopic and the EUS severity grades increased. The accuracy of
      prediction of bleeding or stricture was 100% when endoscopic grade 3a was used as
      a cutoff. For EUS, the highest accuracy was observed in the prediction of
      bleeding (75%) and stricture (100%) when EUS grade MP was used as a cutoff.
      CONCLUSIONS: EUS can be performed safely within 24 hours of ingestive of
      corrosive substances. However, when used in conjunction with conventional
      endoscopic observation, it does not increase the accuracy for prediction of early
      or late complications. Standard endoscopy alone is sufficient for evaluation and
      prediction of bleeding and stricture complications after corrosive injury in the
      upper-GI tract.

PMID- 15557971
TI  - ERCP subsequent to retroperitoneal perforation caused by endoscopic
      sphincterotomy.
AB  - BACKGROUND: Perforation occurs after endoscopic sphincterotomy in 0.4% of cases.
      With recognition of a perforation, the procedure usually is aborted and further
      attempts at ERCP are thought to be precluded by the complication. The aim of this
      study was to determine the timing and the outcome of ERCP after retroperitoneal
      perforation caused by endoscopic sphincterotomy when the initial ERCP was
      incomplete. METHODS: A total of 1787 patients underwent endoscopic sphincterotomy
      during a period of 29 months. A type II duodenal perforation was recognized in 15
      patients, whereupon the ERCP, including further intervention, was halted. Eight
      patients agreed to undergo a second therapeutic ERCP to complete the treatment of
      the primary disease. OBSERVATIONS: Therapeutic ERCP was repeated in all patients
      from 11 to 15 days after the perforation. Treatment was successfully completed in
      all patients without complication. CONCLUSIONS: Therapeutic ERCP may be repeated
      and has a high success rate in patients who sustain a perforation caused by
      endoscopic sphincterotomy.

PMID- 15557972
TI  - Complete closure of a large defect after EMR of a lateral spreading colorectal
      tumor when using a two-channel colonoscope.

PMID- 15557973
TI  - Large-cell neuroendocrine carcinoma of the major duodenal papilla: case report.

PMID- 15557974
TI  - Problematic esophageal stricture: an emerging indication for self-expandable
      silicone stents.

PMID- 15557975
TI  - Asymptomatic aspiration of a capsule endoscope.

PMID- 15557976
TI  - Multiple small-bowel diaphragms: a cause of obscure GI bleeding diagnosed by
      capsule endoscopy.

PMID- 15557977
TI  - Catheter probe EUS-assisted treatment with hemoclips of a colonic Dieulafoy's
      lesion with recurrent bleeding.

PMID- 15557978
TI  - Anisakis in a biopsy specimen from the edge of a gastric ulcer: report of a case.

PMID- 15557979
TI  - Metastatic Merkel cell carcinoma masquerading as colon cancer.

PMID- 15557980
TI  - Diagnosis of a malignant mesothelioma by EUS-guided FNA of a mediastinal lymph
      node.

PMID- 15557981
TI  - Palliation of patients with esophageal cancer and metal stents.

PMID- 15557982
TI  - Sphincter of Oddi manometry and bile crystals.

PMID- 15557986
TI  - The Wellness Wheel, HMO care strategies show great promise.

PMID- 15557987
TI  - From subjects of medicine to subjects of law.

PMID- 15557988
TI  - Regulatory issues in CAM.

PMID- 15557989
TI  - No one seems to care about fraud.

PMID- 15557991
TI  - Obesity, responsibility, and empathy.

PMID- 15557992
TI  - Obesity: addressing a multifactorial disease.

PMID- 15557993
TI  - Obesity--the new majority.

PMID- 15557994
TI  - Childhood diabetes: what the case manager needs to know.

PMID- 15557995
TI  - Assessing and interviewing patients for meaningful behavioral change: Part 2.

PMID- 15557996
TI  - When the diagnosis is Alzheimer's disease: case management as a resource.

PMID- 15557997
TI  - ABC of postacute care.

PMID- 15557998
TI  - Getting the most from an independent review organization.

PMID- 15557999
TI  - Mental health impact of September 11.

PMID- 15558002
TI  - Perinatal toxicity of domestic naphthalene exposure.
AB  - Naphthalene-containing mothballs can cause methemoglobinemia on inhalation. We
      describe a mother with hemolytic anemia and methemoglobinemia associated with
      elevated levels of naphthalene following exposure to mothballs. Her newborn
      infant had identical symptoms requiring mechanical ventilation and an exchange
      transfusion for resolution.

PMID- 15558003
TI  - Intestinal zygomycosis due to Absidia corymbifera mimicking necrotizing
      enterocolitis in a preterm neonate.
AB  - Zygomycosis is a rare fungal disease that occurs in compromised human hosts,
      including the preterm infant. The three clinical forms of zygomycosis are
      cellulitis, disseminated, and gastrointestinal, and the last often mimics
      necrotizing enterocolitis (NEC), complicating the diagnosis. This report details
      a case of primary gastrointestinal zygomycosis due to Absidia corymbifera,
      mimicking NEC, in a preterm infant, and emphasizes features that may lead to
      earlier diagnosis and treatment of future cases.

PMID- 15558004
TI  - Cerebral venous sinus thrombosis in a neonate with homozygous prothrombin G20210A
      genotype.
AB  - We describe a 7-day-old infant who presented with extensive cerebral venous sinus
      thrombosis (CVST) and was found to be homozygous for the prothrombin G20210A gene
      mutation. No other known risk factors for thrombosis were identified.

PMID- 15558005
TI  - Association of glutathione-S-transferase-P1 (GSTP1) polymorphism 105 Ile>val with
      chronic lung disease in preterm infants.

PMID- 15558008
TI  - Time for 'enlightened moderation'.

PMID- 15558009
TI  - Abstracts from the annual scientific meeting of the British Hypertension Society.
      September 13-15, 2004. Cambridge, United Kingdom.

PMID- 15558010
TI  - Autonomous regulation of the anaphase-promoting complex couples mitosis to S
      phase entry.
AB  - Oscillations in cyclin-dependent kinase (CDK) activity drive the somatic cell
      cycle. After entry into mitosis, CDKs activate the anaphase-promoting complex
      (APC), which then promotes cyclin degradation and mitotic exit. The re
      accumulation of cyclin A causes the inactivation of APC and entry into S phase,
      but how cyclin A can accumulate in the presence of active APC has remained
      unclear. Here we show that, during G1, APC autonomously switches to a state
      permissive for cyclin A accumulation. Crucial to this transition is the APC(Cdh1)
      dependent autoubiquitination and proteasomal degradation of the ubiquitin
      conjugating enzyme (E2) UbcH10. Because APC substrates inhibit the
      autoubiquitination of UbcH10, but not its E2 function, APC activity is maintained
      as long as G1 substrates are present. Thus, through UbcH10 degradation and cyclin
      A stabilization, APC autonomously downregulates its activity. This indicates that
      the core of the metazoan cell cycle could be described as a self-perpetuating but
      highly regulated oscillator composed of alternating CDK and APC activities.

PMID- 15558011
TI  - Isolation of cancer stem cells from adult glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common adult primary brain tumor and is
      comprised of a heterogeneous population of cells. It is unclear which cells
      within the tumor mass are responsible for tumor initiation and maintenance. In
      this study, we report that brain tumor stem cells can be identified from adult
      GBMs. These tumor stem cells form neurospheres, possess the capacity for self
      renewal, express genes associated with neural stem cells (NSCs), generate
      daughter cells of different phenotypes from one mother cell, and differentiate
      into the phenotypically diverse populations of cells similar to those present in
      the initial GBM. Having a distinguishing feature from normal NSCs, these tumor
      stem cells can reform spheres even after the induction of differentiation.
      Furthermore, only these tumor stem cells were able to form tumors and generate
      both neurons and glial cells after in vivo implantation into nude mice. The
      identification of tumor stem cells within adult GBM may represent a major step
      forward in understanding the origin and maintenance of GBM and lead to the
      identification and testing of new therapeutic targets.

PMID- 15558012
TI  - Molecular and prognostic distinction between serous ovarian carcinomas of varying
      grade and malignant potential.
AB  - Profiles of gene transcription have begun to delineate the molecular basis of
      ovarian cancer, including distinctions between carcinomas of differing histology,
      tumor progression and patient outcome. However, the similarities and differences
      among the most commonly diagnosed noninvasive borderline (low malignant
      potential, LMP) lesions and invasive serous carcinomas of varying grade (G1, G2
      and G3) have not yet been explored. Here, we used oligonucleotide arrays to
      profile the expression of 12,500 genes in a series of 57 predominantly stage III
      serous ovarian adenocarcinomas from 52 patients, eight with borderline tumors and
      44 with adenocarcinomas of varying grade. Unsupervised and supervised analyses
      showed that LMP lesions were distinct from high-grade serous adenocarcinomas, as
      might be expected; however, well-differentiated (G1) invasive adenocarcinomas
      showed a strikingly similar profile to LMP tumors as compared to cancers with
      moderate (G2) or poor (G3) cellular differentiation, which were also highly
      similar. Comparative genomic hybridization of an independent cohort of five LMP
      and 63 invasive carcinomas of varying grade demonstrated LMP and G1 were again
      similar, exhibiting significantly less chromosomal aberration than G2/G3
      carcinomas. A majority of LMP and G1 tumors were characterized by high levels of
      p21/WAF1, with concomitant expression of cell growth suppressors, gadd34 and BTG
      2. In contrast, G2/G3 cancers were characterized by the expression of genes
      associated with the cell cycle and by STAT-1-, STAT-3/JAK-1/2-induced gene
      expression. The distinction between the LMP-G1 and G2-G3 groups of tumors was
      highly correlated to patient outcome (chi(2) for equivalence of death
      rates=7.681189; P=0.0056, log-rank test). Our results are consistent with the
      recent demonstration of a poor differentiation molecular 'meta-signature' in
      human cancer, and underscore a number of cell-cycle- and STAT-associated targets
      that may prove useful as points of therapeutic intervention for those patients
      with aggressive disease.

PMID- 15558013
TI  - Gene expression signature predicts lymphatic metastasis in squamous cell
      carcinoma of the oral cavity.
AB  - Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma
      of the oral cavity (OSCC). We sought to determine whether the presence of
      metastasis in the regional lymph node could be predicted by a gene expression
      signature of the primary tumor. A total of 18 OSCCs were characterized for gene
      expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with
      differential expression were identified using a permutation technique and
      verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was
      built using a support vector machine, and the accuracy of the rule was evaluated
      using crossvalidation on the original data set and prediction of an independent
      set of four patients. Metastatic primary tumors could be differentiated from
      nonmetastatic primary tumors by a signature gene set of 116 genes. This signature
      gene set correctly predicted the four independent patients as well as associating
      five lymph node metastases from the original patient set with the metastatic
      primary tumor group. We concluded that lymph node metastasis could be predicted
      by gene expression profiles of primary oral cavity squamous cell carcinomas. The
      presence of a gene expression signature for lymph node metastasis indicates that
      clinical testing to assess risk for lymph node metastasis should be possible.

PMID- 15558014
TI  - Identification of novel RARbeta2 transcript variants with short 5'-UTRs in normal
      and cancerous breast epithelial cells.
AB  - Functional significance of RARbeta2 as a putative tumor suppressor gene has been
      studied in breast cancer and other tumors. The long 5'-untranslated region (5'
      UTR) of its transcript with multiple open-reading frames (uORFs) is considered as
      a regulatory unit for translation. Here, for the first time we identified
      RARbeta2 transcript variants with short 5'-UTRs in both normal and malignant
      breast epithelial cells. The 5'-RACE analysis of RARbeta2 mRNA in these cells
      demonstrated the existence of short RARbeta2 transcript variants that are
      identical to the sequence of known RARbeta2, but lack all the uORFs present in
      the full-length 5'-UTR. By RT-PCR analysis, we found that the expression of both
      transcripts with short and full-length 5'-UTR is mediated by retinoic acid, while
      cellular sensitivity is preferentially correlated to upregulation of short
      RARbeta2 transcript variants in response to retinoic acid. The transfection and
      in vitro translation assay indicated that the short 5'-UTR has no inhibitory
      effects on translation, while the presence of full-length 5'-UTR inhibited
      translation by 60%. In addition, no promoter activity was detectable in RARbeta2
      full-length 5'-UTR region. Our data suggest that the RARbeta2 transcript variants
      with short 5'-UTR may serve as major transcripts for RARbeta2 protein translation
      as well as potential targets for retinoids in breast cancer prevention and
      therapy studies.

PMID- 15558015
TI  - Silibinin strongly inhibits growth and survival of human endothelial cells via
      cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications
      for angioprevention and antiangiogenic therapy.
AB  - Recently, we observed that suppression of tumor xenograft growth by silibinin was
      associated with reduction in tumor vasculature and an increased apoptosis. Here,
      we provide evidence for molecular events associated with antiangiogenic efficacy
      of pharmacologically achievable doses of silibinin in endothelial cell culture
      system. Our data show that silibinin almost completely (P<0.001) inhibits growth
      of human umbilical vein endothelial cells (HUVEC) and human microvascular
      endothelial cells (HMVEC-dermal origin) together with induction of cell death in
      a dose- and time-dependent manner. Growth inhibition was associated with a strong
      induction of G1 arrest accompanied by an increase in Kip1/p27, Cip1/p21 and p53.
      Apoptosis induction (up to 14- to 17-fold in both cell lines, P<0.001) was an
      underlying mechanism in silibinin-induced death of endothelial cells. In the
      studies elucidating the molecular events involved in apoptosis, silibinin caused
      loss of mitochondrial membrane potential and an increase in cytochrome c release
      from mitochondria. An increase in Bax and a decrease in Mcl-1 proteins were also
      observed. Silibinin-induced apoptosis involved both caspase-dependent and 
      independent mechanisms. Silibinin also decreased survivin level and inhibited Akt
      and NF-kappaB signaling. Two different PI-3K inhibitors, wortmannin and LY294002,
      showed Akt-independent activation of NF-kappaB. Further, silibinin showed a
      concentration-dependent strong inhibition of capillary tube formation on
      matrigel, retraction and disintegration of preformed capillary network,
      inhibition of matrigel invasion and migration, and a decrease in matrix
      metalloproteinase-2 secretion by HUVEC. Together, these findings identify
      pleiotropic mechanisms for antiangiogenic efficacy of silibinin, and suggest its
      usefulness in angioprevention and antiangiogenic therapy.

PMID- 15558016
TI  - An antitumorigenic role for murine 8S-lipoxygenase in skin carcinogenesis.
AB  - The levels of 8S-lipoxygenase (8S-LOX) expression and of its arachidonic acid
      metabolite, 8-hydroxyeicosatetraenoic acid (8-HETE), are highly elevated in the
      early stages of mouse skin carcinogenesis. On the other hand, several reports
      showing that 8-HETE is also closely associated with keratinocyte differentiation
      raise a question concerning the role of 8S-LOX/8-HETE in skin carcinogenesis. To
      address that question, here we conducted a series of gain-of-function studies.
      Skin targeted loricrin 8S-LOX/C57BL/6J transgenic mice showed a more
      differentiated epidermal phenotype as well as a 64% reduced papilloma development
      in a two-stage skin carcinogenesis protocol. Forced expression of 8S-LOX in MT1/2
      cells, a murine papilloma cell line, also caused a more differentiated appearance
      as well as keratin 1 expression. Overexpression of 8S-LOX in CH72 cells, a murine
      carcinoma cell line, inhibited cell proliferation by 30% in vitro and by 86% in
      in vivo xenografts. Exogenous addition of 5 muM 8-HETE to CH72 cells caused cell
      cycle arrest at the G1 phase. Finally, immunohistochemical analyses showed 8S-LOX
      protein expression was strictly confined to the differentiated compartment of
      mouse skin and throughout tumorigenesis. Collectively, these data suggest that 8S
      LOX plays a role as a prodifferentiating, antitumorigenic, and tumor suppressing
      gene in mouse skin carcinogenesis.

PMID- 15558017
TI  - Silencing of human Int-6 impairs mitosis progression and inhibits cyclin B-Cdk1
      activation.
AB  - The Int-6 protein has been originally identified as the product of a mouse gene
      being a frequent integration site of the mouse mammary tumour virus. Here, we
      show that reducing Int-6 expression by RNA interference in HeLa cells markedly
      alters mitosis progression. Defects in spindle formation, chromosome segregation
      and cytokinesis were observed. These abnormalities of mitosis completion are
      correlated with an inhibition of cyclin B-Cdk1 kinase activity, due to a
      prolonged inhibitory phosphorylated state of Cdk1. In line with this observation,
      the Wee1 tyrosine kinase that negatively controls Cdk1 was less efficiently
      inactivated during G2 in Int-6-depleted cells. These findings support the notion
      that the oncogenic properties associated with alteration of Int-6 originate from
      chromosomal instability.

PMID- 15558018
TI  - CD44 binding through the hemopexin-like domain is critical for its shedding by
      membrane-type 1 matrix metalloproteinase.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a potent modulator of
      pericellular environment through its proteolytic activity and promotes migration,
      invasion, and proliferation of tumor cells. During cell migration, MT1-MMP binds
      to CD44H, a major hyaluronan receptor, through the hemopexin-like (HPX) domain
      and localizes at the migration front. MT1-MMP is also responsible for shedding
      CD44H, which supports CD44H-mediated cell migration. In this study, we asked
      whether the binding of MT1-MMP to CD44H is a prerequisite step for the successive
      shedding. Deletion of the HPX domain deprived MT1-MMP of its shedding activity.
      Furthermore, disruption of the CD44H/MT1-MMP complex by overexpressing the HPX
      fragments resulted in inhibition of the shedding. Thus, the CD44H in the complex
      appears to be the direct substrate of MT1-MMP for shedding. Interestingly, other
      members of the MT-MMP family showed varied extents of CD44H shedding. Domain
      swapping between MT1-MMP and other MT-MMPs revealed that the ability of the HPX
      domains to bind CD44H is conserved among them. However, the shedding activity was
      different depending on the catalytic domains. The conserved binding ability of
      the HPX domains suggests that CD44H may act as a core molecule assembling
      multiple MT-MMPs on the cell surface.

PMID- 15558019
TI  - Protein stability and function of p73 are modulated by a physical interaction
      with RanBPM in mammalian cultured cells.
AB  - Upon a certain DNA damage including cisplatin treatment, p73 is stabilized and
      exerts its growth-suppressive and/or proapoptotic function. However, the precise
      molecular basis by which the intracellular levels of p73 are regulated remains
      unclear. In the present study, we have identified RanBPM as a novel binding
      partner of p73alpha by yeast-based two-hybrid screening, and also found that
      RanBPM has an ability to stabilize p73alpha. GST pull-down assays and co
      immunoprecipitation experiments revealed that RanBPM directly bound to the
      extreme COOH-terminal region of p73alpha, whereas it failed to interact with p53.
      Co-expression of RanBPM with p73alpha resulted in the nuclear translocation of
      RanBPM, and both proteins co-localized in cell nucleus as examined by indirect
      immunofluorescent staining. It is worth noting that the expression of RanBPM
      inhibited the ubiquitination of p73alpha, and thereby prolonged its half-life.
      Subsequent studies demonstrated that the proapoptotic activity of p73alpha was
      significantly enhanced in the presence of RanBPM. Taken together, our present
      findings implicate a novel role for RanBPM in the regulation of p73 stability and
      function.

PMID- 15558020
TI  - Reciprocal relationship in gene expression between FGFR1 and FGFR3: implication
      for tumorigenesis.
AB  - We have previously demonstrated that the expression of FGFR3 is frequently
      downregulated in colorectal carcinoma cells. Here we have shown that FGFR1 is
      overexpressed in colorectal carcinoma cells and the gene expressions between
      FGFR1 and FGFR3 are mutually exclusive. Moreover, we have also shown that the
      disruption of FGFR1 expression by introducing of FGFR1 siRNA was effective in
      elevating FGFR3 expression and tumor suppressive activities. Thus, FGFR1 may
      confer a selectable advantage on clones of cells in colorectal tumorigenesis,
      favoring proliferation, whereas FGFR3 may have the effect of an unfavorable
      negative regulation of progression of the carcinomas to malignancy, promoting
      differentiation. Our results indicate that the reciprocal relationship in gene
      expression between FGFR1 and FGFR3 in colorectal tissue plays an important role
      in the progression of the carcinomas to malignancy.

PMID- 15558021
TI  - MEKK1 regulates the AP-1 dimer repertoire via control of JunB transcription and
      Fra-2 protein stability.
AB  - Activator protein 1 (AP-1) transcription factor dimers are composed of Jun, Fos,
      and ATF member proteins, but the mechanisms that determine AP-1 composition are
      not clearly defined and the function of specific dimers is not well understood.
      MEKK1 is a mitogen-activated protein kinase (MAPK) kinase kinase and an ubiquitin
      ligase that regulates both the extracellular signal-regulated kinase 1/2 and the
      c-Jun amino-terminal kinase. Herein, we demonstrate that MEKK1 regulates the AP-1
      protein repertoire. Both FGF-2 and phorbol ester-inducible urokinase-type
      plasminogen activator (uPA) expression requires AP-1 binding to an enhancer
      element in the uPA promoter, and we have previously shown that FGF-2 or PMA
      induction of uPA expression is strongly dependent on MEKK1. JunB mRNA is
      significantly increased in MEKK1-/- cells, demonstrating that MEKK1 suppresses
      JunB mRNA expression. Upregulation of JunB expression in MEKK1-/- cells forms an
      inhibitory AP-1 complex that binds to the uPA promoter and inhibits uPA
      transcription. MEKK1 also regulates Fra-2 protein stability by inducing Fra-2
      ubiquitination and degradation. MEKK1 regulates AP-1-dependent gene expression by
      regulating the expression, activity and degradation of component members of the
      AP-1 complex. Controlling the repertoire of a transcription factor complex is a
      newly defined function for an MAPK kinase kinase.

PMID- 15558022
TI  - beta-Catenin activates the growth factor endothelin-1 in colon cancer cells.
AB  - Endothelin-1 (EDN1) is a growth factor that is frequently produced by cancer
      cells and plays a critical role in tumorigenesis. However, the molecular
      mechanism controlling the expression of EDN1 in cancers is unknown. Constitutive
      activation of beta-catenin pathway is responsible for the initiation of the vast
      majority of colon cancers. Here we show that the EDN1 gene is directly regulated
      by beta-catenin in colon cancer cells. A specific DNA element within the EDN1
      promoter is required for activation, and is associated with beta-catenin's
      cognate DNA binding partner, TCF4, in vivo. Inhibition of beta-catenin signaling
      results in lowered expression of EDN1, while enhancement of beta-catenin
      signaling leads to further activation of the gene. Significantly elevated EDN1
      expression occurs in 80% of primary human colon cancers, consistent with it being
      a direct target of beta-catenin. Furthermore, EDN1 is able to rescue colon cancer
      cells from growth arrest and apoptosis resulting from inhibition of beta-catenin
      signaling, implicating a key role of EDN1 in promoting the oncogenic function of
      beta-catenin. These results indicate EDN1 overexpression as a major cause in
      colon cancers and reveal further details of the genetic programs responsible for
      tumorigenesis of colon cancers.

PMID- 15558023
TI  - Endogenous angiogenin in endothelial cells is a general requirement for cell
      proliferation and angiogenesis.
AB  - Angiogenin is an angiogenic protein that undergoes nuclear translocation in
      endothelial cells where it accumulates in the nucleolus and stimulates rRNA
      transcription, a rate-limiting step in ribosome biogenesis, protein translation,
      and cell growth. Here, we report that angiogenin is required for cell
      proliferation induced by various other angiogenic proteins including acidic and
      basic fibroblast growth factors (aFGF and bFGF), epidermal growth factor (EGF),
      and vascular endothelial growth factor (VEGF). Downregulation of angiogenin in
      endothelial cells by small interfering RNA (siRNA) and antisense results in a
      decrease in rRNA transcription, ribosome biogenesis, and cell proliferation
      induced by these angiogenic factors. Inhibitors of the nuclear translocation of
      angiogenin abolish the angiogenic activities of these factors. Stable angiogenin
      antisense transfection in HeLa cells reduces tumor angiogenesis in athymic mice
      despite the elevated expression level of bFGF and VEGF. Thus, nuclear angiogenin
      assumes an essential role in endothelial cell proliferation and is necessary for
      angiogenesis induced by other angiogenic factors. Angiogenin-stimulated rRNA
      transcription in endothelial cells may thus serve as a crossroad in the process
      of angiogenesis induced by various angiogenic factors.

PMID- 15558024
TI  - Amiloride augments TRAIL-induced apoptotic death by inhibiting phosphorylation of
      kinases and phosphatases associated with the P13K-Akt pathway.
AB  - We have previously shown that low extracellular pH (pHe) promotes cell killing by
      the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this
      study, we examined whether amiloride, an inhibitor of the Na(+)/H(+) antiporter
      capable of lowering the intracellular pH (pHi), can potentiate TRAIL-induced
      apoptotic death. Human prostate adenocarcinoma DU-145 cells were treated with
      various concentrations of TRAIL (10-200 ng/ml) and/or amiloride (0.1-1 mM) for 4
      h. Amiloride, which caused little or no cytotoxicity by itself, enhanced TRAIL
      induced apoptosis. The TRAIL-mediated activation of caspase, and PARP (poly (ADP
      ribose) polymerase) cleavage were both promoted by amiloride. Western blot
      analysis showed that combined treatment with TRAIL and amiloride did not change
      the levels of TRAIL receptors (death receptor (DR)4, DR5, and DcR2 (decoy
      recepter 2) or antiapoptotic proteins (FLICE-inhibitory protein (FLIP), inhibitor
      of apoptosis (IAP), and Bcl-2). However, unlike pHe, amiloride promoted the
      dephosphorylation of Akt. Interestingly, amiloride also induced the
      dephosphorylation of P13K (phosphatidylinositol 3-kinase) and PDK-1
      (phosphoinositide-dependent kinase-1) kinases along with PTEN (phosphatase and
      tensin homolog deleted on chromosome 10) and PP1alpha phosphatases. In vitro
      kinase assays revealed that amiloride inhibited phosphorylation of kinases and
      phosphatases by competing with ATP. Taken together, the present studies suggest
      that amiloride enhances TRAIL-induced cytotoxicity by inhibiting phosphorylation
      of the PI3K-Akt pathway-associated kinases and phosphatases.

PMID- 15558025
TI  - Tumor-prone phenotype of the DDB2-deficient mice.
AB  - DDB2 is an essential subunit of the damaged-DNA recognition factor DDB, which is
      involved in global genomic repair in human cells. Moreover, DDB2 is mutated in
      the repair-deficiency disease xeroderma pigmentosum (Group E). Expression of DDB2
      in human cells is induced by P53, BRCA1 and by ionizing radiation. The DDB2
      protein associates with transcriptional activator and coactivator proteins. In
      addition, DDB2 in conjunction with DDB1 associates with cullin 4A and the
      Cop9/signalosome. We generated a mouse strain deficient for DDB2 (DDB2-/-).
      Consistent with the human disease (XP-E), the DDB2-/- mice were susceptible to UV
      induced skin carcinogenesis. We observed a significant difference in the initial
      rate of cyclobutane pyrimidine dimer (CPD)-removal from the skin following UV
      irradiation. Also, the DDB2-deficient mice exhibited a significantly reduced life
      span compared to their wild-type littermates. Moreover, unlike other XP-deficient
      mice, the DDB2-deficient mice developed spontaneous malignant tumors at a high
      rate between the ages of 20 and 25 months. The observations suggest that, in
      addition to DNA repair, the other interactions of DDB2 are significant in its
      tumor suppression function.

PMID- 15558026
TI  - A central domain of cyclin D1 mediates nuclear receptor corepressor activity.
AB  - Regulation of nuclear receptor activity is the focus of numerous ongoing studies
      to develop novel therapies for the treatment of hormone-related cancer. Although
      cyclin D1 functions to control the activity of several nuclear receptors, the
      region(s) of the protein responsible for such transcriptional comodulation remain
      poorly defined. Herein, we map the region of cyclin D1 required for binding and
      repression of the androgen receptor (AR) to a central, exclusively alpha-helical
      domain. Deletion of this domain disrupted AR binding and corepressor activity.
      Further investigations showed that this domain is sufficient for AR interaction
      and possesses the ability to bind histone deacetylase 3. Strikingly,
      overexpression of this repressor region attenuates cell cycle progression in
      prostatic adenocarcinoma cells. The requirement of this domain for nuclear
      receptor repression was conserved with respect to thyroid hormone receptor beta
      1, whereas cyclin D1 activation of the estrogen receptor occurred independently
      of the central region. Together, these data identify a minimal repression module
      within cyclin D1 and demonstrate that the coactivator and corepressor functions
      of cyclin D1 are distinct. In addition, our data suggest that properties of the
      cyclin D1 central domain could be exploited to develop novel prostate cancer
      therapeutics.

PMID- 15558027
TI  - Functional identification of a BAC clone from 16q24 carrying a senescence gene
      SEN16 for breast cancer cells.
AB  - We have identified an 85 kb BAC clone, 346J21, that carries a cell senescence
      gene (SEN16), previously mapped to 16q24.3. Transfer and retention of 346J21 in
      breast cancer cell lines leads to growth arrest after 8-10 cell doublings,
      accompanied by the appearance of characteristic senescent cell morphology and
      senescence-associated acid beta-galactosidase activity. Loss of transferred BAC
      results in reversion to the immortal growth phenotype of the parental cancer cell
      lines. BAC 346J21 restores senescence in the human breast cancer cell lines,
      MCF.7 and MDA-MB468, and the rat mammary tumor cell line LA7, but not in the
      human glioblastoma cell line T98G. We postulate that inactivation of both copies
      of SEN16 is required for the immortalization of breast epithelial cells at an
      early stage of tumorigenesis. Positional mapping of 346J21 shows that SEN16 is
      distinct from other candidate tumor suppressor genes reported at 16q24.

PMID- 15558028
TI  - Signaling properties and expression in normal and tumor tissues of two
      phospholipase C epsilon splice variants.
AB  - Phospholipase Cepsilon (PLCepsilon) is a novel member of phosphoinositide
      specific phospholipase C enzymes with a unique regulatory link to Ras GTP-ases.
      In the present studies, we establish existence of two splice variants
      (PLCepsilon1a and PLCepsilon1b) derived from human PLCepsilon1 gene. When
      expressed in COS or HEK293 cells, PLCepsilon1a and PLCepsilon1b have similar
      potential to be stimulated by diverse signaling pathways via tyrosine kinase and
      G-protein coupled receptors and share the ability to function as an effector of
      Ras. The expression pattern shows broader mRNA expression of PLCepsilon1a in
      normal tissues; furthermore, in most cell lines expressing PLCepsilon,
      PLCepsilon1a is the only splice variant present. Analysis of normal/tumor matched
      pairs derived from colon and rectum demonstrates greatly reduced expression
      levels in tumor tissues. Further studies in a colorectal tumor cell line lacking
      PLCepsilon show restoration of transcription of PLCepsilon1a and PLCepsilon1b by
      demethylating agent 5-aza-2'-deoxycytidine, suggesting epigenetic silencing
      through hypermethylation. In addition, expression of exogenous PLCepsilon in this
      cell line demonstrates inhibitory effects of PLCepsilon on cell viability and
      proliferation. Taken together, our findings suggest that regulatory mechanisms
      controlling expression of PLCepsilon, broadened by diversity introduced by splice
      variants, could play important role in PLCepsilon regulation in normal and tumor
      cells.

PMID- 15558029
TI  - Cytoskeletal modification of Rho guanine nucleotide exchange factor activity:
      identification of a Rho guanine nucleotide exchange factor as a binding partner
      for Sept9b, a mammalian septin.
AB  - Small GTPase Rho and septin family proteins are thought to be related to
      tumorigenesis. We have identified a Rho-guanine nucleotide exchange factor (GEF)
      as a binding partner for a mammalian septin Sept9b using yeast two-hybrid
      screening. We termed this molecule septin-associated RhoGEF (SA-RhoGEF).
      Molecular dissection analyses indicated that the C-terminal area of SA-RhoGEF
      exhibited binding to the N-terminal variable region of Sept9b. SA-RhoGEF was
      found by immunoprecipitation analysis to associate with septin complexes in REF52
      fibroblast cells, maybe through direct interaction with Sept9b.
      Immunofluorescence analyses revealed the colocalization of SA-RhoGEF and Sept9b
      along with actin stress fibers in REF52 cells, and their colocalization along
      stress fibers was most likely to depend on their mutual interaction. In transient
      expression analyses, Sept9b inhibited SA-RhoGEF-dependent Rho activation in COS7
      and HeLa cells. SA-RhoGEF and its fragments expressed in REF52 cells altered
      endogenous septin filament structures. To our knowledge, SA-RhoGEF is the first
      molecule providing a link between septins and Rho signaling.

PMID- 15558030
TI  - Characterization of VIK-1: a new Vav-interacting Kruppel-like protein.
AB  - Binding partners of the Src homology domains of Vav-1 were characterized by a two
      hybrid screening of a Jurkat cell cDNA library. One of the isolated clones
      encoded a new protein named VIK that belongs to the Kruppel-like zinc-finger gene
      family. Genome mapping showed that a single gene positioned at chromosome 7q22.1
      generated three possible isoforms containing alternative domains such as proline
      rich and Kruppel-associated box A or B repressor domains. The isolated isoform,
      VIK-1, did not contain such motifs but presented six tandemly arranged zinc
      fingers and consensus Kruppel H-C links. VIK-1 interacted both with Vav-1 and
      cyclin-dependent kinase 4 through two independent domains and corresponded to a
      Vav C-Src homology domain (SH)3 partner able to shuttle between the nucleus and
      the cytoplasm exhibiting functional nuclear addressing and export sequences. The
      results indicated a restricted expression of the protein during the G1 phase and
      its overexpression resulted in an inhibition of the cell-cycle progression that
      was reversed in the presence of Vav 1. Thus, this ubiquitous factor provides a
      first link between Vav-1 and the cell-cycle machinery.

PMID- 15558031
TI  - Eps8 controls actin-based motility by capping the barbed ends of actin filaments.
AB  - Actin filament barbed-end capping proteins are essential for cell motility, as
      they regulate the growth of actin filaments to generate propulsive force. One
      family of capping proteins, whose prototype is gelsolin, shares modular
      architecture, mechanism of action, and regulation through signalling-dependent
      mechanisms, such as Ca(2+) or phosphatidylinositol-4,5-phosphate binding. Here we
      show that proteins of another family, the Eps8 family, also show barbed-end
      capping activity, which resides in their conserved carboxy-terminal effector
      domain. The isolated effector domain of Eps8 caps barbed ends with an affinity in
      the nanomolar range. Conversely, full-length Eps8 is auto-inhibited in vitro, and
      interaction with the Abi1 protein relieves this inhibition. In vivo, Eps8 is
      recruited to actin dynamic sites, and its removal impairs actin-based propulsion.
      Eps8-family proteins do not show any similarity to gelsolin-like proteins. Thus,
      our results identify a new family of actin cappers, and unveil novel modalities
      of regulation of capping through protein-protein interactions. One established
      function of the Eps8-Abi1 complex is to participate in the activation of the
      small GTPase Rac, suggesting a multifaceted role for this complex in actin
      dynamics, possibly through the participation in alternative larger complexes.

PMID- 15558032
TI  - A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis
      in intestinal cells of Caenorhabditis elegans.
AB  - Redundant gene function frequently hampers investigations of the physiological
      roles of mammalian proteins. This is the case for Eps8, a receptor tyrosine
      kinase (RTK) substrate that participates in the activation of the Rac-specific
      guanine nucleotide-exchange function of Sos1 (refs 2-5), thereby regulating actin
      remodelling by RTKs. EPS8-knockout mice, however, exhibit no evident phenotype,
      owing to the redundant function of three other EPS8-related genes. Here we show
      that in the nematode Caenorhabditis elegans, only one orthologue of the EPS8 gene
      exists, which gives rise to two alternatively spliced isoforms, EPS-8A and EPS
      8B, differing at their carboxyl termini. In the nematode, eps-8 is essential for
      embryonic development. Furthermore, EPS-8A, but not EPS-8B, is specifically
      required for proper apical morphogenesis in the intestinal cells. This latter
      phenotype could be precisely correlated with a previously unknown actin barbed
      end-capping activity, which is present in the C terminus of the EPS-8A isoform.
      Therefore, nematode genetics allowed not only the unmasking of distinct EPS-8
      linked phenotypes, but also the definition of a novel function for this molecule
      in actin dynamics.

PMID- 15558033
TI  - Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent
      on autophagy genes.
AB  - Programmed cell death can be divided into several categories including type I
      (apoptosis) and type II (autophagic death). The Bcl-2 family of proteins are well
      characterized regulators of apoptosis, and the multidomain pro-apoptotic members
      of this family, such as Bax and Bak, act as a mitochondrial gateway where a
      variety of apoptotic signals converge. Although embryonic fibroblasts from
      Bax/Bak double knockout mice are resistant to apoptosis, we found that these
      cells still underwent a non-apoptotic death after death stimulation. Electron
      microscopic and biochemical studies revealed that double knockout cell death was
      associated with autophagosomes/autolysosomes. This non-apoptotic death of double
      knockout cells was suppressed by inhibitors of autophagy, including 3-methyl
      adenine, was dependent on autophagic proteins APG5 and Beclin 1 (capable of
      binding to Bcl-2/Bcl-x(L)), and was also modulated by Bcl-x(L). These results
      indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also
      controls non-apoptotic programmed cell death that depends on the autophagy genes.

PMID- 15558034
TI  - Nuclear actin and myosin I are required for RNA polymerase I transcription.
AB  - The presence of actin and nuclear myosin I (NMI) in the nucleus suggests a role
      for these motor proteins in nuclear functions. We have investigated the role of
      actin and nuclear myosin I (NMI) in the transcription of ribosomal RNA genes
      (rDNA). Both proteins are associated with rDNA and are required for RNA
      polymerase I (Pol I) transcription. Microinjection of antibodies against actin or
      NMI, as well as short interfering RNA-mediated depletion of NMI, decreased Pol I
      transcription in vivo, whereas overexpression of NMI augmented pre-rRNA
      synthesis. In vitro, recombinant NMI activated Pol I transcription, and
      antibodies to NMI or actin inhibited Pol I transcription both on naked DNA and
      pre-assembled chromatin templates. Whereas actin associated with Pol I, NMI bound
      to Pol I through the transcription-initiation factor TIF-IA. The association with
      Pol I requires phosphorylation of TIF-IA at Ser 649 by RSK kinase, indicating a
      role for NMI in the growth-dependent regulation of rRNA synthesis.

PMID- 15558035
TI  - Humidity-induced magnetization and magnetic pole inversion in a cyano-bridged
      metal assembly.
AB  - In general, magnetic properties of bulk magnetic materials are independent of the
      humidity of the environment. To obtain a magnetic material that has humidity
      sensitive characteristics, water vapour must penetrate the lattice and act on
      spin sites. Nanoporous materials composed of metal-assembled complexes may be
      expected to display some humidity response because materials in this category can
      show functionalities such as gas storage and molecular recognition. Here, we
      demonstrate humidity-induced reversible variations in the magnetic properties of
      cyano-bridged cobalt(II)-manganese(II)-chromium(III) metal assemblies. The
      observed magnetic humidity response is due to adsorption and desorption of a
      ligand water molecule on the cobalt ion, which changes cobalt (II) between a 6-
      and 4-fold coordination geometry and switches the magnetic interaction between
      ferromagnetic coupling and antiferromagnetic coupling.

PMID- 15558036
TI  - Bond- versus site-centred ordering and possible ferroelectricity in manganites.
AB  - Transition metal oxides with a perovskite-type structure constitute a large group
      of compounds with interesting properties. Among them are materials such as the
      prototypical ferroelectric system BaTiO(3), colossal magnetoresistance manganites
      and the high-T(c) superconductors. Hundreds of these compounds are magnetic, and
      hundreds of others are ferroelectric, but these properties very seldom coexist.
      Compounds with an interdependence of magnetism and ferroelectricity could be very
      useful: they would open up a plethora of new applications, such as switching of
      magnetic memory elements by electric fields. Here, we report on a possible way to
      avoid this incompatibility, and show that in charge-ordered and orbitally ordered
      perovskites it is possible to make use of the coupling between magnetic and
      charge ordering to obtain ferroelectric magnets. In particular, in manganites
      that are less than half doped there is a type of charge ordering that is
      intermediate between site-centred and bond-centred. Such a state breaks inversion
      symmetry and is predicted to be magnetic and ferroelectric.

PMID- 15558037
TI  - Serious graft-versus-host disease after hematopoietic cell transplantation
      following nonmyeloablative conditioning.
AB  - The efficacy of allogeneic hematopoietic cell transplantation (HCT) after
      nonmyeloablative conditioning depends on the balance between the desirable
      antineoplastic effects of donor cells weighed against the undesirable morbidity
      of graft-versus-host disease (GVHD). Development of serious acute or chronic GVHD
      was analyzed retrospectively in 171 consecutive patients, who had related or
      unrelated nonmyeloablative HCT for hematologic malignancies. GVHD was defined as
      serious when it resulted in (1) death, (2) disability, (3) three or more major
      infections in 1 year, (4) prolonged hospitalization or (5) suicide or
      hospitalization for suicidal ideation. According to this definition, 43 of 171
      (25%) patients developed serious GVHD with a median follow-up of 30 (range, 12
      65) months. The incidence of serious GVHD was similar after related and unrelated
      HCT. Among the 43 patients with serious GVHD, 20 had grade III-IV acute GVHD, and
      30 had extensive chronic GVHD. Among the 171 patients, seven had grade III acute
      GVHD and 84 had extensive chronic GVHD that did not meet criteria for serious
      GVHD. Assessment of serious GVHD provides additional useful information to acute
      GVHD grades and classification of limited and extensive chronic GVHD in
      describing the overall risk and impact complications caused by donor cells.

PMID- 15558038
TI  - Engraftment kinetics of human CD34+ cells from cord blood and mobilized
      peripheral blood co-transplanted into NOD/SCID mice.
AB  - We have reported short periods of post transplant neutropenia in human patients
      co-transplanted with cord blood (CB) and low numbers of haploidentical mobilized
      peripheral blood (MPB) CD34+ cells. To investigate the effect that the proportion
      of MPB to CB cells may have on engraftment kinetics, we have co-transplanted
      fixed numbers of human CB CD34+ cells mixed with different numbers of MPB CD34+
      cells into NOD/SCID mice. We periodically quantified the proportion of human
      cells and the relative contribution of MPB and CB cells to the human engraftment
      on marrow aspirates. At the lowest MPB/CB ratios (5 : 1, 10 : 1), the
      contribution of CB cells predominated at all time points analyzed, and in three
      out of four experiments MPB cell contributions progressively decreased from day
      +15. At higher MPB/CB ratios, MPB cells had a more important contribution to both
      early and late engraftment, with the highest cell ratio resulting in only
      marginal CB cell engraftment. Therefore, our results showed greater potential, on
      a per cell basis, of human CB vs MPB cells for competitive sustained engraftment
      in the xenogeneic model used, which was only abrogated by the co-infusion of very
      high numbers of MPB cells.

PMID- 15558039
TI  - Second allografts for relapsed hematologic malignancies: feasibility of using a
      different donor.
AB  - A second allogeneic hematopoietic stem cell transplant (HSCT) for relapsed
      hematologic malignancies is an option in select patients after an initial
      allograft has failed. If the original donor is not available, a different donor
      may have to be considered. We report our experience of performing a second
      allogeneic HSCT using a different donor in patients with relapsed leukemia and
      lymphoma. In a 5-year period, six patients underwent a second allograft with
      myeloablative conditioning using a different donor. Four of these were
      retransplanted using a matched-unrelated donor. Four of the patients (67%) remain
      progression-free at a median follow-up of 32 months (range 3-72). There were no
      cases of transplant-related mortality. We conclude that a second allogeneic HSCT
      using a different donor is a viable option for selected patients relapsing after
      an allograft if the original donor is not available.

PMID- 15558040
TI  - Optimal scheduling to reduce morbidity of involved field radiotherapy with
      transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma
      Group Study.
AB  - This study evaluated delivery of involved field radiotherapy (IFRT) with
      transplantation for lymphomas timed to minimise toxicity. Patients transplanted
      for lymphoma had infradiaphragmatic disease irradiated pre-transplant and
      supradiaphragmatic disease post transplant. A total of 31 patients were studied,
      with a median follow-up duration of 4 years. Transplant conditioning was
      according to clinician preference. In all, 14 patients had pre-transplant
      abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre
      transplant IFRT). Grade III-IV haematological toxicity from pre-transplant IFRT
      occurred in three patients and from post transplant IFRT in 10 patients. Pre
      transplant IFRT had no effect on haematological recovery post transplant, but was
      associated with a trend towards increased gastrointestinal toxicity (P = 0.094).
      Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two
      patients failed in involved sites after completion of protocol radiotherapy. One
      case of myelodysplasia has been reported. As sequenced in this study, IFRT was
      feasible and produced a low incidence of severe pulmonary and haematological
      toxicities. Patient selection, field size and radiotherapy dose warrant further
      study.

PMID- 15558041
TI  - Antilymphocyte/thymocyte globulin for graft versus host disease prophylaxis:
      efficacy and side effects.
AB  - Antilymphocyte/thymocyte globulins (ALGs/ATGs) have now been used for over 30
      years in the setting of hemopoietic stem cell transplants (HSCT), with the aim of
      preventing graft-versus-host disease (GvHD). This is true especially for
      transplants from alternative donors. In this review, we will be discussing
      available published and unpublished data on the advantages and disadvantages of
      using ALG/ATG before or after an allogeneic HSCT. These studies show that ALG/ATG
      significantly reduce the incidence and severity of acute and chronic GvHD.
      Unfortunately, they also show that immune deficiency is a more prolonged and
      infectious complication more frequent in patients receiving ALG/ATG, suggesting
      the importance of aggressive monitoring of viral and fungal infections. In
      particular, the emerging problem of Epstein-Barr virus (EBV) infections and EBV
      related lymphoproliferative disorders will be discussed, together with the use of
      pre-emptive therapy with rituximab. I personally believe ALG/ATG has an important
      role in allogeneic HSCT, especially today with the increasing use of peripheral
      blood transplants and the consequent high risk of chronic GvHD. ALG/ATG should be
      used with caution, and the negative consequences must be understood and possibly
      prevented.

PMID- 15558042
TI  - Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and
      myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic
      stem cell transplant (HSCT).
AB  - Pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with
      monosomy 7 is associated with poor disease-free survival when treated by
      conventional chemotherapy, immunosuppression or supportive measures.
      Hematopoietic stem cell transplant (HSCT) may improve outcomes; however, data to
      support this are limited. To better understand the curative potential of HSCT in
      these patients, all cases of AML and MDS with monosomy 7 treated by two
      transplant programs (1992 to present) were reviewed. A total of 16 patients were
      treated, all by allogeneic HSCT. Primary diagnoses were MDS (N = 5), therapy
      related MDS (N = 3), AML (N = 5) and therapy-related AML (N = 3). In all, 11
      patients (69%) survive event-free at 2 years with median follow-up of 986 days
      (range 330-2011 days). Toxicity caused deaths of the five nonsurviving patients,
      four of whom were transplanted with active leukemia. Allogeneic HSCT is effective
      therapy for childhood AML and MDS associated with monosomy 7, particularly for
      patients with AML in complete remission and MDS.

PMID- 15558043
TI  - Syndrome 'X' in adult female recipients of bone marrow transplantation for
      haematological malignancies.

PMID- 15558044
TI  - Vascular leak syndrome and serositis as an unusual manifestation of chronic graft
      versus-host disease in nonmyeloablative transplants.

PMID- 15558045
TI  - Adoptive transfer of small numbers of DX5+ cells alleviates graft-versus-host
      disease in a murine model of semiallogeneic bone marrow transplantation: a
      potential role for NKT lymphocytes.
AB  - Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes
      with important immunemodulatory effects. Our aim was to evaluate the effect of
      transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a
      murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 x 107
      splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 x Balb/c)F1
      recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was
      performed. Recipient mice were followed for histological parameters of GVHD
      associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic
      lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations.
      It was seen that adoptive transfer of 4.5 x 106 DX5+ cells significantly
      alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved
      survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to
      severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation
      with the number of transplanted DX5+ cells was noted (maximal effect with
      transplantation of 4.5 x 106 DX5+ cells). Tolerance induction was associated with
      an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes
      and a shift towards a Th2-type cytokine profile, manifested by decreased IL
      12/IL10, IL-12/IL-4, IFNgamma/IL-10, and IFNgamma/IL-4 ratios. Transplantation of
      DX5+ cells holds promise as a novel therapeutic measure for GVHD.

PMID- 15558046
TI  - Lack of interferon response in animals to naked siRNAs.
AB  - RNA interference (RNAi) is rapidly becoming the method of choice for the
      elucidation of gene function and the identification of drug targets. As with
      other oligonucleotide-based strategies, RNAi is envisioned to ultimately be
      useful as a human therapeutic. Unlike previous nucleic acid therapeutics, small
      interfering RNAs have the potential to elicit immune responses via interactions
      with Toll-like receptor 3 and trigger interferon responses like long, double
      stranded RNA and its analogs, such as poly(I:C). Recently, the safety of siRNAs
      has been questioned because they have been shown to trigger an interferon
      response in cultured cells. We show here that it is possible to administer naked,
      synthetic siRNAs to mice and downregulate an endogenous or exogenous target
      without inducing an interferon response.

PMID- 15558047
TI  - Improved monomeric red, orange and yellow fluorescent proteins derived from
      Discosoma sp. red fluorescent protein.
AB  - Fluorescent proteins are genetically encoded, easily imaged reporters crucial in
      biology and biotechnology. When a protein is tagged by fusion to a fluorescent
      protein, interactions between fluorescent proteins can undesirably disturb
      targeting or function. Unfortunately, all wild-type yellow-to-red fluorescent
      proteins reported so far are obligately tetrameric and often toxic or disruptive.
      The first true monomer was mRFP1, derived from the Discosoma sp. fluorescent
      protein "DsRed" by directed evolution first to increase the speed of maturation,
      then to break each subunit interface while restoring fluorescence, which
      cumulatively required 33 substitutions. Although mRFP1 has already proven widely
      useful, several properties could bear improvement and more colors would be
      welcome. We report the next generation of monomers. The latest red version
      matures more completely, is more tolerant of N-terminal fusions and is over
      tenfold more photostable than mRFP1. Three monomers with distinguishable hues
      from yellow-orange to red-orange have higher quantum efficiencies.

PMID- 15558048
TI  - Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen
      specific anti-tumor immunity.
AB  - Tumor vaccines represent a promising therapeutic approach, but thus far have
      achieved only limited success in the clinic. The major challenge is to find a
      means of overcoming inhibitory immune regulatory mechanisms and eliciting
      effective T-cell responses to antigens preferentially expressed by tumor cells.
      Here we show that the stimulatory capacity of dendritic cells (DCs) and the
      magnitude of adaptive immunity are critically regulated by the suppressor of
      cytokine signaling (SOCS) 1 in DCs. Silencing SOCS1 in antigen-presenting DCs
      strongly enhances antigen-specific anti-tumor immunity. Our findings indicate
      that SOCS1 represents an inhibitory mechanism for qualitatively and
      quantitatively controlling antigen presentation by DCs and the magnitude of
      adaptive immunity. This study has implications for understanding the regulation
      of antigen presentation and for developing more effective tumor vaccines by
      silencing the critical brake in antigen presentation.

PMID- 15558049
TI  - Structure of human POT1 bound to telomeric single-stranded DNA provides a model
      for chromosome end-protection.
AB  - The POT1 (protection of telomeres 1) protein binds the single-stranded overhang
      at the ends of chromosomes in diverse eukaryotes. It is essential for chromosome
      end-protection in the fission yeast Schizosaccharomyces pombe, and it is involved
      in regulation of telomere length in human cells. Here, we report the crystal
      structure at a resolution of 1.73 A of the N-terminal half of human POT1 (hPOT1)
      protein bound to a telomeric single-stranded DNA (ssDNA) decamer, TTAGGGTTAG, the
      minimum tight-binding sequence indicated by in vitro binding assays. The
      structure reveals that hPOT1 contains two oligonucleotide/ oligosaccharide
      binding (OB) folds; the N-terminal OB fold binds the first six nucleotides,
      resembling the structure of the S. pombe Pot1pN-ssDNA complex, whereas the second
      OB fold binds and protects the 3' end of the ssDNA. These results provide an
      atomic-resolution model for chromosome end-capping.

PMID- 15558050
TI  - Structure of a purine-purine wobble base pair in the decoding center of the
      ribosome.
AB  - Here we report the crystal structures of I.C and I.A wobble base pairs in the
      context of the ribosomal decoding center, clearly showing that the I.A base pair
      is of an I(anti).A(anti) conformation, as predicted by Crick. Additionally, the
      structures enable the observation of changes in the anticodon to allow purine
      purine base pairing, the 'widest' base pair geometry allowed in the wobble
      position.

PMID- 15558051
TI  - Dynamic opening of DNA during the enzymatic search for a damaged base.
AB  - Uracil DNA glycosylase (UDG) removes uracil from U.A or U.G base pairs in genomic
      DNA by extruding the aberrant uracil from the DNA base stack. A question in
      enzymatic DNA repair is whether UDG and related glycosylases also use an
      extrahelical recognition mechanism to inspect the integrity of undamaged base
      pairs. Using NMR imino proton exchange measurements we find that UDG
      substantially increases the equilibrium constant for opening of T-A base pairs by
      almost two orders of magnitude relative to free B-DNA. This increase is brought
      about by enzymatic stabilization of an open state of the base pair without
      increasing the rate constant for spontaneous base pair opening. These findings
      indicate a passive search mechanism in which UDG uses the spontaneous opening
      dynamics of DNA to inspect normal base pairs in a rapid genome-wide search for
      uracil in DNA.

PMID- 15558052
TI  - The role of modifications in codon discrimination by tRNA(Lys)UUU.
AB  - The natural modification of specific nucleosides in many tRNAs is essential
      during decoding of mRNA by the ribosome. For example, tRNA(Lys)(UUU) requires the
      modification N6-threonylcarbamoyladenosine at position 37 (t(6)A37), adjacent and
      3' to the anticodon, to bind AAA in the A site of the ribosomal 30S subunit.
      Moreover, it can only bind both AAA and AAG lysine codons when doubly modified
      with t(6)A37 and either 5-methylaminomethyluridine or 2-thiouridine at the wobble
      position (mnm(5)U34 or s(2)U34). Here we report crystal structures of modified
      tRNA anticodon stem-loops bound to the 30S ribosomal subunit with lysine codons
      in the A site. These structures allow the rationalization of how modifications in
      the anticodon loop enable decoding of both lysine codons AAA and AAG.

PMID- 15558053
TI  - Structural insights into FtsZ protofilament formation.
AB  - The prokaryotic tubulin homolog FtsZ polymerizes into a ring structure essential
      for bacterial cell division. We have used refolded FtsZ to crystallize a tubulin
      like protofilament. The N- and C-terminal domains of two consecutive subunits in
      the filament assemble to form the GTPase site, with the C-terminal domain
      providing water-polarizing residues. A domain-swapped structure of FtsZ and
      biochemical data on purified N- and C-terminal domains show that they are
      independent. This leads to a model of how FtsZ and tubulin polymerization evolved
      by fusing two domains. In polymerized tubulin, the nucleotide-binding pocket is
      occluded, which leads to nucleotide exchange being the rate-limiting step and to
      dynamic instability. In our FtsZ filament structure the nucleotide is
      exchangeable, explaining why, in this filament, nucleotide hydrolysis is the rate
      limiting step during FtsZ polymerization. Furthermore, crystal structures of FtsZ
      in different nucleotide states reveal notably few differences.

PMID- 15558054
TI  - Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53
      function in tumors.
AB  - In tumors that retain wild-type p53, its tumor-suppressor function is often
      impaired as a result of the deregulation of HDM-2, which binds to p53 and targets
      it for proteasomal degradation. We have screened a chemical library and
      identified a small molecule named RITA (reactivation of p53 and induction of
      tumor cell apoptosis), which bound to p53 and induced its accumulation in tumor
      cells. RITA prevented p53-HDM-2 interaction in vitro and in vivo and affected p53
      interaction with several negative regulators. RITA induced expression of p53
      target genes and massive apoptosis in various tumor cells lines expressing wild
      type p53. RITA suppressed the growth of human fibroblasts and lymphoblasts only
      upon oncogene expression and showed substantial p53-dependent antitumor effect in
      vivo. RITA may serve as a lead compound for the development of an anticancer drug
      that targets tumors with wild-type p53.

PMID- 15558055
TI  - Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal
      encephalitis.
AB  - West Nile virus (WNV), a mosquito-borne single-stranded (ss)RNA flavivirus,
      causes human disease of variable severity. We investigated the involvement of
      Toll-like receptor (Tlr) 3, which recognizes viral double-stranded (ds)RNA, on
      WNV infection. Tlr3-deficient (Tlr3(-/-)) mice were more resistant to lethal WNV
      infection and had impaired cytokine production and enhanced viral load in the
      periphery, whereas in the brain, viral load, inflammatory responses and
      neuropathology were reduced compared to wild-type mice. Peripheral WNV infection
      led to a breakdown of the blood-brain barrier and enhanced brain infection in
      wild-type but not in Tlr3(-/-) mice, although both groups were equally
      susceptible upon intracerebroventricular administration of the virus. Tumor
      necrosis factor-alpha receptor 1 signaling is vital for blood-brain barrier
      compromise upon Tlr3 stimulation by dsRNA or WNV. Collectively, WNV infection
      leads to a Tlr3-dependent inflammatory response, which is involved in brain
      penetration of the virus and neuronal injury.

PMID- 15558056
TI  - Protein microarrays for multiplex analysis of signal transduction pathways.
AB  - We have developed a multiplexed reverse phase protein (RPP) microarray platform
      for simultaneous monitoring of site-specific phosphorylation of numerous
      signaling proteins using nanogram amounts of lysates derived from stimulated
      living cells. We first show the application of RPP microarrays to the study of
      signaling kinetics and pathway delineation in Jurkat T lymphocytes. RPP
      microarrays were used to profile the phosphorylation state of 62 signaling
      components in Jurkat T cells stimulated through their membrane CD3 and CD28
      receptors, identifying a previously unrecognized link between CD3 crosslinking
      and dephosphorylation of Raf-1 at Ser259. Finally, the potential of this
      technology to analyze rare primary cell populations is shown in a study of
      differential STAT protein phosphorylation in interleukin (IL)-2-stimulated
      CD4(+)CD25(+) regulatory T cells. RPP microarrays, prepared using simple
      procedures and standard microarray equipment, represent a powerful new tool for
      the study of signal transduction in both health and disease.

PMID- 15558057
TI  - Prevention of cholesterol gallstone disease by FXR agonists in a mouse model.
AB  - Cholesterol gallstone disease is characterized by several events, including
      cholesterol precipitation in bile, increased bile salt hydrophobicity and
      gallbladder inflammation. Here, we describe the same phenotype in mice lacking
      the bile acid receptor, FXR. Furthermore, in susceptible wild-type mice that
      recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR
      agonist prevented sequelae of the disease. These effects were mediated by FXR
      dependent increases in biliary bile salt and phospholipid concentrations, which
      restored cholesterol solubility and thereby prevented gallstone formation. Taken
      together, these results indicate that FXR is a promising therapeutic target for
      treating or preventing cholesterol gallstone disease.

PMID- 15558058
TI  - Adiponectin-mediated modulation of hypertrophic signals in the heart.
AB  - Patients with diabetes and other obesity-linked conditions have increased
      susceptibility to cardiovascular disorders. The adipocytokine adiponectin is
      decreased in patients with obesity-linked diseases. Here, we found that pressure
      overload in adiponectin-deficient mice resulted in enhanced concentric cardiac
      hypertrophy and increased mortality that was associated with increased
      extracellular signal-regulated kinase (ERK) and diminished AMP-activated protein
      kinase (AMPK) signaling in the myocardium. Adenovirus-mediated supplemention of
      adiponectin attenuated cardiac hypertrophy in response to pressure overload in
      adiponectin-deficient, wild-type and diabetic db/db mice. In cultures of cardiac
      myocytes, adiponectin activated AMPK and inhibited agonist-stimulated hypertrophy
      and ERK activation. Transduction with a dominant-negative form of AMPK reversed
      these effects, suggesting that adiponectin inhibits hypertrophic signaling in the
      myocardium through activation of AMPK signaling. Adiponectin may have utility for
      the treatment of hypertrophic cardiomyopathy associated with diabetes and other
      obesity-related diseases.

PMID- 15558059
TI  - Small proline-rich proteins 2 are noncoordinately upregulated by IL-6/STAT3
      signaling after bile duct ligation.
AB  - Small proline-rich proteins 2 (SPRR2) are coordinately expressed with other
      epidermal differential complex (EDC) genes in the skin. They function as
      crosslinking proteins that form bridges between other proteins that comprise the
      cornified cell envelope, which is the major barrier against the environment. IL-6
      is invariably produced at sites of biliary tract injury and IL-6-deficient (IL-6(
      /-)) mice show impaired barrier function after bile duct ligation (BDL).
      Screening microarray analysis identified noncoordinate expression of SPRR2 as a
      candidate gene that is: (a) expressed in biliary epithelial cells (BEC); (b) IL-6
      responsive; and (c) potentially related to biliary barrier function. Therefore,
      we studied in detail the regulation of BEC SPRR2A expression, in vitro; and
      tested the hypothesis that if BEC SPRR2 expression contributes to biliary barrier
      function, it should be increased after BDL in IL-6-wild type (IL-6(+/+)) mice and
      not in IL-6(-/-) mice. In vitro studies confirmed that IL-6/gp130-signaling,
      mediated primarily by signal transducer and activator of transcription 3 (STAT3),
      stimulated noncoordinate BEC SPRR2 expression. In vivo, noncoordinate
      upregulation of BEC SPRR2 expression after BDL was seen in the IL-6(+/+) mice and
      was unrelated to squamous metaplasia. IL-6(-/-) mice showed deficient BEC SPRR2
      expression after BDL associated with impaired barrier function, as evidenced by
      smaller diameters of obstructed ducts, decreased bile volume, and an inability to
      form 'white bile' compared to IL-6(+/+) mice at 12 weeks after BDL. IL-6
      replacement therapy reversed the barrier defect in IL-6(-/-) mice after BDL,
      coincident with recovery of SPRR2A expression. SPRR2 in diseased mouse and human
      liver localized subjacent to the apical plasma membrane of BEC lining bile ducts,
      but was more diffusely expressed throughout the cytoplasm of cholangioles. In
      conclusion, BEC IL-6/gp130/STAT3 signaling noncoordinately upregulates BEC SPRR2
      that appears to contribute to modification of the biliary barrier under
      conditions of stress.

PMID- 15558060
TI  - Splenic transposition is superior to caudal shunt as a model of murine total
      hepatic ischemia.
AB  - Murine total hepatic ischemia (THI) followed by reperfusion without shunting of
      the portal vein induces significant lethality in rodents due to intestinal
      congestion. Two methods have been promulgated to study THI and reperfusion in
      mice without intestinal congestion: subcutaneous splenic transposition which
      creates a portosystemic shunt via epigastric vessels, and a caudal shunt with 30%
      hepatectomy, which creates a portosystemic shunt via the small remnant of
      remaining caudal lobe. We compared outcome, inflammatory response and hepatic
      injury due to THI and reperfusion in these two models. Female C57BL/6 mice
      underwent ST, caudal shunt or no surgery prior to having 30 min of total hepatic
      ischemia followed by 60 min of reperfusion. Survival, surgical complications,
      serum AST/ALT and IL-6 were determined. Apoptotic and necrotic hepatocytes were
      identified by morphological criteria. Complication rates for the ST and caudal
      shunt procedures were 6.7 and 20%, respectively. Subsequent mortality rates
      following THI and 60 min reperfusion were 5.9 and 50% in mice with ST and caudal
      shunt, respectively. Both groups had elevated serum AST/ALT concentrations.
      However, in mice undergoing caudal shunt, AST/ALT levels were also significantly
      increased even without THI. The number of apoptotic hepatocytes after THI and
      reperfusion in mice following caudal shunt was significantly higher compared with
      those of ST (P<0.001). Both ST and caudal shunt can be used in models of THI and
      reperfusion to prevent significant lethality due to intestinal congestion.
      However, ST is a simple, safe and suitable model, whereas caudal shunt requires
      manipulation of the liver, and is associated with significant hepatic injury and
      morbidity.

PMID- 15558061
TI  - Respiratory control by ventral surface chemoreceptor neurons in rats.
AB  - A long-standing theory posits that central chemoreception, the CNS mechanism for
      CO(2) detection and regulation of breathing, involves neurons located at the
      ventral surface of the medulla oblongata (VMS). Using in vivo and in vitro
      electrophysiological recordings, we identify VMS neurons within the rat
      retrotrapezoid nucleus (RTN) that have characteristics befitting these elusive
      chemoreceptors. These glutamatergic neurons are vigorously activated by CO(2) in
      vivo, whereas serotonergic neurons are not. Their CO(2) sensitivity is unaffected
      by pharmacological blockade of the respiratory pattern generator and persists
      without carotid body input. RTN CO(2)-sensitive neurons have extensive dendrites
      along the VMS and they innervate key pontomedullary respiratory centers. In
      brainstem slices, a subset of RTN neurons with markedly similar morphology is
      robustly activated by acidification and CO(2). Their pH sensitivity is intrinsic
      and involves a background K(+) current. In short, the CO(2)-sensitive neurons of
      the RTN are good candidates for the long sought-after VMS chemoreceptors.

PMID- 15558062
TI  - Light-activated ion channels for remote control of neuronal firing.
AB  - Neurons have ion channels that are directly gated by voltage, ligands and
      temperature but not by light. Using structure-based design, we have developed a
      new chemical gate that confers light sensitivity to an ion channel. The gate
      includes a functional group for selective conjugation to an engineered K(+)
      channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light
      drives the azobenzene moiety into its extended trans configuration, allowing the
      blocker to reach the pore. Short-wavelength light generates the shorter cis
      configuration, retracting the blocker and allowing conduction. Exogenous
      expression of these channels in rat hippocampal neurons, followed by chemical
      modification with the photoswitchable gate, enables different wavelengths of
      light to switch action potential firing on and off. These synthetic
      photoisomerizable azobenzene-regulated K(+) (SPARK) channels allow rapid, precise
      and reversible control over neuronal firing, with potential applications for
      dissecting neural circuits and controlling activity downstream from sites of
      neural damage or degeneration.

PMID- 15558063
TI  - Motor activation prior to observation of a predicted movement.
AB  - Previous research has shown that some of the same motor regions are activated
      both when performing and when observing a movement. Here we demonstrate in human
      subjects that such motor activity also occurs prior to observing someone else's
      action. This suggests that the mere knowledge of an upcoming movement is
      sufficient to excite one's own motor system, enabling people to anticipate,
      rather than react to, others' actions.

PMID- 15558064
TI  - Human anterior cingulate neurons and the integration of monetary reward with
      motor responses.
AB  - The human dorsal anterior cingulate cortex (dACC) has been implicated in
      cognitive processes that have been proposed to play a role in integrating
      contextual information needed to select or modify appropriate motor responses. In
      humans, however, there has been little direct evidence tying the dACC to the
      integration of contextual information and behavioral response. We used single
      neuron recordings from human subjects to evaluate the role of the dACC in reward
      based decision making. Subjects undergoing planned surgical cingulotomy performed
      a task where they were instructed to make specific movements in response to
      changing monetary rewards. In many neurons, activity increased in response to a
      diminished reward, and was also predictive of the movement ultimately made. After
      dACC ablation, subjects made selectively more errors when they were required to
      change movement based on reward reduction. These findings suggest that the dACC
      in humans plays an important role in linking reward-related information with
      alternative actions.

PMID- 15558065
TI  - How emotion enhances the feeling of remembering.
AB  - Studies examining memories of arousing 'real-life' events show that emotion
      heightens the feeling of remembering, without necessarily enhancing the objective
      accuracy of the memories. We measured brain activity associated with the feeling
      of remembering emotional and neutral photos. Subjects indicated whether
      recognition was accompanied by a recollection of details about the study episode
      ('remember') or not ('know'). 'Remember' judgments were boosted for emotional
      photos, but accuracy did not differ. For neutral photos, 'remember' judgments
      were related to enhanced activity in the parahippocampal cortex, previously
      related to recognition of visual details, which one might expect to supply the
      retrieval clues for a 'remember' judgment. In contrast, 'remember' judgments for
      emotional photos were associated with enhanced activity in the amygdala,
      suggesting that subjects rely on arousal and perceptual fluency to evaluate these
      memories. For the first time, we identify the neural mechanisms underlying the
      enhanced feeling of remembering for emotional events.

PMID- 15558066
TI  - Similar network activity from disparate circuit parameters.
AB  - It is often assumed that cellular and synaptic properties need to be regulated to
      specific values to allow a neuronal network to function properly. To determine
      how tightly neuronal properties and synaptic strengths need to be tuned to
      produce a given network output, we simulated more than 20 million versions of a
      three-cell model of the pyloric network of the crustacean stomatogastric ganglion
      using different combinations of synapse strengths and neuron properties. We found
      that virtually indistinguishable network activity can arise from widely disparate
      sets of underlying mechanisms, suggesting that there could be considerable animal
      to-animal variability in many of the parameters that control network activity,
      and that many different combinations of synaptic strengths and intrinsic membrane
      properties can be consistent with appropriate network performance.

PMID- 15558067
TI  - Dynamic molecular interactions linking the T cell antigen receptor to the actin
      cytoskeleton.
AB  - T cell receptor (TCR) engagement leads to actin polymerization at the site of T
      cell contact with antigen-presenting cells. Here we have studied the dynamic
      activity of proteins involved in regulating actin polymerization in live T cells
      after activation. Two such adaptor proteins, Nck and the Wiskott-Aldrich syndrome
      protein (WASp), were recruited to the TCR during initial T cell activation, where
      they colocalized with the tyrosine kinase Zap70. The recruitment of Nck and WASp
      depended on TCR-induced tyrosine phosphorylation and the LAT and SLP-76 adaptors.
      Nck and WASp migrated peripherally and accumulated at an actin-rich
      circumferential ring. Thus, actin polymerization regulated by the TCR begins at
      the TCR. Molecules recruited to the TCR regulate actin polymerization and this
      process drives plasma membrane movement and cellular spreading.

PMID- 15558069
TI  - Characterisation of breast fine-needle aspiration biopsies by centrosome
      aberrations and genomic instability.
AB  - Recent studies have suggested that aneuploidy in malignant tumours could be a
      consequence of centrosome aberrations. Using immunofluorescence analysis with an
      antibody against gamma-tubulin and DNA image cytometry, we measured centrosome
      aberrations and DNA ploidy patterns in fine-needle aspiration biopsies (FNABs) of
      58 breast lesions. Benign lesions did not show any centrosome aberrations. DNA
      diploid carcinomas showed a mean percentage of cells with centrosomal defects of
      2.1%. The aneuploid invasive carcinomas could be divided into two subgroups by
      their significantly (P=0.0003) different percentage of cells with centrosome
      aberrations (2.0 and 10.3%, respectively) and their significantly (P=0.0003)
      different percentage of cells with nonmodal DNA content values determined by the
      Stemline Scatter Index (SSI), a measure of genomic instability. The percentage of
      cells with centrosome aberrations demonstrated a positive, linear correlation
      with the corresponding SSI (r=0.82, P<0.0001) and loss of tissue differentiation
      (r=0.78, P<0.0001). Our results indicate the percentage of cells with centrosome
      aberrations as being sufficient to divide the investigated tumours into three
      significantly different groups: benign lesions with no centrosomal aberrations,
      and two malignant tumour types with mean values of 2.1 and 9.6% of centrosomal
      defects, respectively. Together, these results demonstrate that centrosome
      aberrations correlate with genomic instability and loss of tissue
      differentiation. Furthermore, this study shows the feasibility of centrosomal
      analysis in FNAB of the breast and suggests centrosomal aberrations as possessing
      diagnostic and prognostic value.

PMID- 15558070
TI  - Microvascular density and hypoxia-inducible factor pathway in pancreatic
      endocrine tumours: negative correlation of microvascular density and VEGF
      expression with tumour progression.
AB  - Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible
      factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular
      mechanisms of their angiogenesis are not fully delineated. The aim of this study
      is to evaluate angiogenesis and expression of HIF-related molecules in a series
      of patients with pancreatic endocrine tumours (PETs). The expression of vascular
      endothelial growth factor (VEGF), HIF-1alpha, HIF-2alpha and carbonic anhydrase 9
      (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared
      to microvascular density (MVD), endothelial proliferation, tumour stage and
      survival. Microvascular density was very high in PETs and associated with a low
      endothelial index of proliferation. Microvascular density was significantly
      higher in benign PETs than in PETs of uncertain prognosis, well-differentiated
      and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels
      mm(-2), respectively, P < 0.0001). Well-differentiated tumours had high
      cytoplasmic VEGF and HIF-1alpha expression. Poorly differentiated carcinomas were
      associated with nuclear HIF-1alpha and membranous CA9 expression. Low MVD (P =
      0.0001) and membranous CA9 expression (P = 0.0004) were associated with a poorer
      survival. Contrary to other types of cancer, PETs are highly vascularised, but
      poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD
      significantly decreases. The regulation of HIF signalling appears to be specific
      in pancreatic endocrine tumours.

PMID- 15558071
TI  - A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the
      second-line treatment of non-small-cell lung cancer. The DISTAL 01 study.
AB  - Docetaxel (75 mg m(-2) 3-weekly) is standard second-line treatment in advanced
      non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a
      weekly schedule (33.3 mg m(-2) for 6 weeks) improved quality of life (QoL), a
      phase III study was performed with 220 advanced NSCLC patients, < or =75 years,
      ECOG PS < or =2. QoL was assessed by EORTC questionnaires and the Daily Diary
      Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough
      and hair loss significantly favoured the weekly schedule, while diarrhoea was
      worse. DDC analysis showed that loss of appetite and overall condition were
      significantly worse in the 3-week arm in the first week, while nausea and loss of
      appetite were more severe in the weekly arm in the third week. Response rate and
      survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI
      0.77-1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia,
      febrile neutropenia and hair loss; any grade 3-4 haematologic toxicity was
      significantly more frequent in the standard arm (25 vs 6%). The weekly schedule
      could be preferred for patients candidate to receive docetaxel as second-line
      treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and
      no evidence of strikingly different effect on survival.

PMID- 15558072
TI  - Oestrogen receptor status, pathological complete response and prognosis in
      patients receiving neoadjuvant chemotherapy for early breast cancer.
AB  - The aim of this study was to ascertain if oestrogen receptor (ER) status predicts
      for pathological complete response (pCR) to neoadjuvant chemotherapy in operable
      breast cancer, and the effects of pCR on survival. Using a single-institution
      database, 435 patients were identified, who received neoadjuvant chemotherapy for
      operable breast cancer and were eligible for the analysis. Patients whose tumours
      were ER negative were more likely to achieve a pCR than patients who were ER
      positive (21.6 vs 8.1%, P<0.001). Owing to a strong correlation between ER status
      and grade, these variables were not shown to be independent predictors of pCR.
      Overall survival (OS) was better in those patients who achieved a pCR compared to
      those who did not (5-year OS 91 vs 73%; P=0.02). This was still the case when
      only patients with ER-negative tumours were examined (5-year OS 90 vs 52%,
      P=0.005), but not in the subset of patients with ER-positive tumours (5-year OS
      93 vs 79%; P=0.3). Therefore, patients with ER-negative tumours were found to be
      more likely to achieve a pCR to neoadjuvant chemotherapy than those with ER
      positive tumours, and pathological response did not have prognostic significance
      in patients with ER-positive tumours.

PMID- 15558073
TI  - Clinical anticancer drug development: targeting the cyclin-dependent kinases.
AB  - Cell division involves a cyclical biochemical process composed of several step
      wise reactions that have to occur once per cell cycle. Dysregulation of cell
      division is a hallmark of all cancers. Genetic and epigenetic mechanisms
      frequently result in deranged expression and/or activity of cell-cycle proteins
      including the cyclins, cyclin-dependent kinases (Cdks), Cdk inhibitors and
      checkpoint control proteins. The critical nature of these proteins in cell
      cycling raises hope that targeting them may result in selective cytotoxicity and
      valuable anticancer activity.

PMID- 15558074
TI  - Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic
      significance.
AB  - Gastric cancer is the second most common cancer in the world and the fifth
      leading cause of cancer-related death in Taiwan. To improve the survival of
      gastric cancer patients, biomarkers for early detection and effective anticancer
      therapy are required. An essential first step is to profile gene expression in
      gastric cancer and identify genes that are aberrantly expressed, and to do this
      cDNA microarrays were performed. The clinic-pathologic correlation and prognostic
      significance of the aberrantly expressed genes were evaluated to identify novel
      biomarkers of gastric cancer. Fresh surgical samples of tumour tissue and
      matching noncancerous mucosa were obtained immediately after gastric resection in
      43 patients. Secreted Protein, Acidic and Rich in Cysteine (SPARC)
      (Osteonectins), one of the most highly expressed genes in both intestinal and
      diffuse gastric cancers in our microarray results, was selected for further
      study. The overexpression of SPARC was verified using real-time quantitative
      reverse transcription-polymerase chain reaction (Q-RT-PCR), Northern blot and
      immunohistochemical staining. The expression of SPARC in tumour tissues was, on
      average, 4.27-fold increased (95% CI 2.68-5.85) compared to adjacent noncancerous
      mucosa (P<0.001). The expression of SPARC was higher in advanced (T2, T3 and T4)
      cancer compared to the early (T1) cancer (P=0.048) with regard to depth of wall
      invasion. Higher expression of SPARC was significantly associated with lymph node
      metastasis (P<0.001), lymphatic invasion (P=0.004) and perineural invasion
      (P=0.047). Expression of SPARC in patients in stage II and above was
      significantly higher than those in stage I (P=0.017). The 3-year survival of
      patients with lower expression of SPARC was significantly better than those with
      a higher expression (log rank P=0.047). These data indicate the potential of
      SPARC as a prognostic marker for gastric cancer.

PMID- 15558075
TI  - Having a regular physician and attempted weight loss after screening for
      hypertension or hypercholesterolemia.
AB  - OBJECTIVE: To examine the relationship between having a regular physician,
      results of screening tests for cardiovascular risk (hypertension,
      hypercholesterolemia) and efforts to lose weight among obese adults. DESIGN:
      Analysis of a population-based telephone survey (2002 Behavioral Risk Factor
      Surveillance System). SETTING: Four states (Iowa, South Carolina, South Dakota,
      Virginia) in the US. PARTICIPANTS: Adults (> or =18 y old) who were obese (body
      mass index > or =30 kg/m(2)) (unweighted n=1735). MAIN OUTCOME MEASURES:
      Currently attempting to lose weight; changes in diet or exercise as strategies to
      lose weight. RESULTS: Obese individuals with a personal physician were more
      likely to report attempts to lose weight in the face of screening normal for
      hypertension or hypercholesterolemia than those without a personal physician
      (75.6 vs 60.5% for hypercholesterolemia, P=0.03; 74.6 vs 57.7% for hypertension,
      P=0.01). In adjusted models, obese individuals screening normal for hypertension
      but having a personal physician were significantly more likely to attempt to lose
      weight than individuals without a personal physician (OR 1.71, 95% CI 1.12-2.60).
      CONCLUSIONS: Having a regular physician is associated with a higher likelihood of
      attempted weight loss among obese individuals who believe that they do not have
      hypertension or hypercholesterolemia, than their counterparts with no regular
      physician. This suggests a previously unrecognized benefit of having a personal
      physician.

PMID- 15558076
TI  - Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption
      and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice.
AB  - OBJECTIVE: To investigate the effect of SR141716, a selective CB1 receptor
      antagonist, on energy expenditure and on glucose uptake in isolated soleus muscle
      of Lep(ob)/Lep(ob) mice. DESIGN: Female Lep(ob)/Lep(ob) mice (8-10 weeks old)
      were treated with SR141716 (10 mg/kg, i.p. once daily) or vehicle for 7 days.
      MEASUREMENTS: Oxygen consumption, daily food and water intake, body weight and
      glucose uptake in isolated soleus muscle. RESULTS: SR141716 (10 mg/kg, i.p. once
      daily) resulted in a significant reduction of daily food intake (P<0.01) and body
      weight (P<0.05) 5 days after daily treatment. Body weight continued to be lower
      for the rest of the treatment period (P<0.05). There was no significant
      difference in body weight between the pair-fed and vehicle-treated animals. A 7
      day treatment with SR141716 (10 mg/kg, i.p. once daily) caused 37% increase in
      basal oxygen consumption compared to that of vehicle-treated (90 min mean;
      P<0.01), and a significant 68% increase in glucose uptake in isolated soleus
      muscle preparations. CONCLUSION: It is concluded that SR141716 has a direct
      effect on energy expenditure suggesting that the antiobesity effect of SR141716
      is due to activation of thermogenesis in addition to the initial hypophagia. The
      increase in soleus muscle glucose uptake with SR141716 treatment may contribute
      to the improved glycaemia seen in the previous studies.

PMID- 15558077
TI  - Reduced expression of the Sp4 gene in mice causes deficits in sensorimotor gating
      and memory associated with hippocampal vacuolization.
AB  - HF-1B/SP4:, a member of the Sp1 family of transcription factors, is expressed
      restrictively in the developing nervous system and most abundantly in adult
      hippocampus in mice. Here, we report the generation of hypomorphic Sp4 allele
      mice, in which the Sp4 deficiency can be rescued by the expression of Cre
      recombinase. Vacuolization was detected in the hippocampal gray matter of the
      mutant Sp4-deficient mice. Expression analysis of Sp4 mutant hippocampi revealed
      an age-dependent decrease in neurotrophin-3 expression in the dentate granule
      cells. Hypomorphic Sp4 mutant mice displayed robust deficits in both sensorimotor
      gating and contextual memory. The restoration of Sp4 expression, via a Cre
      dependent rescue strategy, completely rescued all the observed molecular,
      histological and behavioral abnormalities. Our studies thus reveal a novel Sp4
      pathway that is essential for hippocampal integrity and modulates behavioral
      processes relevant to psychiatric disorders.

PMID- 15558078
TI  - Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited.
AB  - Inositol, a simple six-carbon sugar, forms the basis of a number of important
      intracellular signaling molecules. Over the last 35 years, a series of
      biochemical and cell biological experiments have shown that lithium (Li(+))
      reduces the cellular concentration of myo-inositol and as a consequence
      attenuates signaling within the cell. Based on these observations, inositol
      depletion was proposed as a therapeutic mechanism in the treatment of bipolar
      mood disorder. Recent results have added significant new dimensions to the
      original hypothesis. However, despite a number of clinical studies, this
      hypothesis still remains to be either proven or refuted. In this review of our
      current knowledge, I will consider where the inositol-depletion hypothesis stands
      today and how it may be further investigated in the future.

PMID- 15558079
TI  - Analysis of the RELN gene as a genetic risk factor for autism.
AB  - Several genome-wide screens have indicated the presence of an autism
      susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at
      7q22 within this region is the candidate gene reelin (RELN). RELN encodes a
      signaling protein that plays a pivotal role in the migration of several neuronal
      cell types and in the development of neural connections. Given these
      neurodevelopmental functions, recent reports that RELN influences genetic risk
      for autism are of significant interest. The total data set consists of 218
      Caucasian families collected by our group, 85 Caucasian families collected by
      AGRE, and 68 Caucasian families collected at Tufts University were tested for
      genetic association of RELN variants to autism. Markers included five single
      nucleotide polymorphisms (SNPs) and a repeat in the 5'-untranslated region (5'
      UTR). Tests for association in Duke and AGRE families were also performed on four
      additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Family-based
      association analyses (PDT, Geno-PDT, and FBAT) were used to test for association
      of single-locus markers and multilocus haplotypes with autism. The most
      significant association identified from this combined data set was for the 5'-UTR
      repeat (PDT P-value=0.002). These analyses show the potential of RELN as an
      important contributor to genetic risk in autism.

PMID- 15558080
TI  - Severe kyphoscoliosis causing marked displacement and rotation of right kidney
      with acute kinking of right ureter resulting in hydronephrosis.

PMID- 15558081
TI  - Spinal cord injuries due to diving accidents.
AB  - STUDY DESIGN: Retrospective study and data analysis. OBJECTIVE: To investigate
      and analyse the main features of spinal cord injuries due to diving accidents
      accepted in our Centre from June 1978 to December 2002. SETTING: Regional Spinal
      Unit of Florence, Italy. INTRODUCTION: Diving accidents mostly occur in a young
      and healthy population and most of the patients develop tetraplegia with a severe
      lifelong disability. From 1978 to 2002, 65 patients with spinal injuries due to
      diving accidents were admitted to the Regional Spinal Unit of Florence. MATERIAL
      AND METHODS: A retrospective study was conducted by analysing data stored in our
      local computerized database. We considered the vertebral injury, ASIA-ISCOS
      neurological classification on admission and discharge, gender, age at the time
      of injury, month of injury, treatment of vertebral lesion, length of stay in the
      Spinal Unit, neurological outcome, and complications. Data were analysed
      statistically by using the Fisher's exact test and logistic regression. RESULTS:
      In all, 62/65 patients were males (95%). Mean age at injury time: 22 years. On
      admission, 35/65 were neurologically complete ASIA A (54%), while 16 were
      classified ASIA B, 7 ASIA C and 7 ASIA D, according to the ASIA-ISCOS
      neurological standard of classification. C6 was the most common neurological
      motor level (40%) and C5 the most common vertebral injury level. In all, 36/65
      (55%) patients underwent surgical treatment. Mean hospitalization time was 5
      months. No neurological deterioration was recorded. In all, 20/65 (31%) patients
      improved neurologically and 16/20 (80%) of those had received surgical treatment.
      In all, 15/65 (23%) patients had complications and one patient died during the
      hospitalization period. CONCLUSIONS AND DISCUSSION: Patients whose vertebral
      lesions were surgically treated had a better neurological outcome than
      conservatively treated ones. Teardrop fractures showed worse neurological outcome
      as compared with burst fractures. Neurological improvement was more present in
      initially incomplete lesions. Treatment with high dose methylprednisolone during
      the first 8 h after trauma seemed to influence the neurological outcome
      positively. Age was also an important factor in influencing the neurological
      outcome.

PMID- 15558082
TI  - Patient-staff agreement in the perception of spinal cord lesioned patients'
      problems, emotional well-being, and coping pattern.
AB  - STUDY DESIGN: Matched patient/staff study. OBJECTIVES: To investigate spinal cord
      lesion (SCL) rehabilitation staff perceptions of SCL patient problems, coping
      efforts, and well-being, and to compare these evaluations with patient self
      reports of the same aspects. SETTINGS: Spinal Unit, Sahlgrenska University
      Hospital, Goteborg, Sweden. METHODS: In all, 29 persons with SCL and 24 members
      of the caring staff participated. Each patient was matched to a staff person
      actually involved in his or her care. The participants completed a study-specific
      questionnaire containing 45 SCL-related problems covering six problem areas:
      somatic symptoms, functional limitations, role problems, family-related problems,
      psychosocial problems, and emotional problems. Coping activities were assessed by
      a self-report 47-item questionnaire covering eight aspects of coping: self-trust,
      problem focusing, acceptance, fatalism, resignation, protest, minimization, and
      social trust. The patients were instructed to respond to the items included in
      the questionnaires according to their situation during the last week, while staff
      members were instructed to reply as 'they thought that their matched patient
      would answer'. RESULTS: Moderate but statistically significant correlations were
      demonstrated between patient and staff ratings of most investigated problem
      areas. However, the staff systematically overestimated patients' emotional as
      well as family problems, and tended to underestimate patients' reported coping
      ability and mental health. Staff were most accurate in assessing patients'
      physical symptoms, functional limitations, and role problems, but less accurate
      in their perception of less visible symptoms. CONCLUSION: Relatively high
      agreement between patients and staff concerning patients' problems and states is
      possible to obtain in a caring setting. This may be more related to the quality
      of caring in the studied unit than to the study methodology used. Small units
      with high staff density and a long stay and/or prolonged contact with the
      patients probably facilitate communication with and knowledge about the patients.
      Interventions aimed at increasing staff awareness of patients' coping efforts may
      further improve staff ability to understand and support patients in their
      adaptation process.

PMID- 15558083
TI  - Post traumatic distress symptoms following spinal cord injury: a comparative
      review of European samples.
AB  - OBJECTIVE: To highlight any cross-cultural differences in the prevalence of post
      traumatic distress (PTD), and the type of coping strategies implemented following
      spinal cord injury (SCI). DESIGN: Cross-sectional questionnaire. SETTING: A
      spinal cord rehabilitation unit in the UK, and six Swiss and German (CH/DE)
      spinal injury centres. METHOD: A total of 85 SCI individuals in the UK, and 71 in
      CH/DE were evaluated on levels of PTD using the Impact of Event Scale (IES), and
      depressive symptomatology using the Beck Depression Inventory or the Berne
      Questionnaire of Well-Being at up to 6 months postinjury. In addition, the coping
      strategies utilised by the two samples were assessed using the COPE measure.
      RESULTS: No significant difference between the two samples was noted with regard
      to levels of PTD determined by the total score on the IES, although there was a
      tendency for a higher rate in the UK. Approximately 20 and 10% of both samples
      scored above the clinical cutoff on the IES subscales of intrusion and avoidance,
      respectively. No significant difference was found to exist between the rate of
      PTD in the SCI CH/DE sample and the able-bodied sample in Switzerland. A lower
      prevalence of depression was noted in the CH/DE sample. The CH/DE sample scored
      higher on the use of positive reinterpretation and growth, suppression of
      competing activities, active and restraint coping, whereas the UK sample scored
      higher on the use of humour as a coping strategy. Overall, denial, focusing on
      and venting of emotions, mental disengagement and suppression of competing
      activities were associated with PTD. CONCLUSION: No cross-cultural differences in
      the level of PTD seem apparent between the UK and CH/DE populations. Future
      research should focus on determining what protects individuals from developing
      PTD following SCI.

PMID- 15558084
TI  - Location of urethral arteries by colour Doppler ultrasound.
AB  - STUDY DESIGN: A case report. SETTING: Regional Spinal Injuries Centre, Southport,
      UK. CASE REPORT: A 56-year-old male with complete paraplegia at T-4 underwent
      visual internal urethrotomy of bulbous urethral stricture with a cold knife at 12
      o'clock position. There was brisk arterial bleeding. Despite receiving
      antibiotics, this patient developed hypotension, tachycardia and tachypnoea. He
      was resuscitated and mechanical ventilation was instituted. After he recovered
      from this life-threatening episode of urinary tract-related sepsis, colour
      Doppler ultrasound imaging of bulbous urethra was performed to locate urethral
      arteries. In the bulbous urethra, single urethral artery was seen at 12 o'clock
      position. CONCLUSION: Since the sites of urethral arteries vary among patients,
      it is advisable to assess individually the location of urethral arteries
      preoperatively and plan the site of incision accordingly. Persons with injury to
      cervical or upper dorsal spinal cord have decreased cardiac and respiratory
      reserve as well as alteration in immune function. Therefore, all possible
      measures should be taken to prevent acute blood loss and bacteraemia in this
      group of patients.

PMID- 15558085
TI  - Influence of Different Techniques of Laboratory Construction on the Fracture
      Resistance of Fiber-Reinforced Composite (FRC) Bridges.
AB  - The aim of the current investigation is to evaluate optimal pontic and retainer
      fiber positions for Polyethylene fiber-reinforced composite (FRC) restorations.
      In series I notch disc specimens were used to mimic loading cuspal regions of
      pontics. Four groups (n=15/group; codes A to D) were prepared from Artglass
      composite. Groups A to C were reinforced with polyethylene fibers, and group D
      was an unreinforced control. Fibers were positioned either around (A), beneath
      the notch (B), or at the disc base (C). Specimens were stored in distilled water
      at 37 degrees C for 24 h before testing to failure (CHS=1mm/min) in a universal
      testing machine. Mean torque to failure values ranked [P< 0.05; one-way analysis
      of variance (ANOVA)] as follows A = B > C = D. In series II five groups of three
      unit bridges (n =5/group; codes A to E) were prepared from Artglass dental
      composite without (group A) or with (groups B to E) different Connect fiber
      reinforcement locations/techniques. Bridges were cemented using 2 bond resin
      cement to a standardized substructure. After storage, as per series I, bridges
      were loaded mid-pontic region to failure. One-way ANOVA showed no significant
      (P=0.08) difference between test groups. The research hypothesis was that notched
      disc and 3 unit bridge test techniques would discriminate equally between fiber
      reinforced specimens and an unreinforced composite control was rejected.

PMID- 15558086
TI  - Survey of dental prophylaxes rendered by pediatric dentists in New England.
AB  - BACKGROUND: The objective of this anonymous postal survey was to assess the
      provision of dental prophylaxis by pediatric dentists in New England. METHODS:
      The questionnaire survey was sent by first class mail in September, 2001 to all
      217 American Academy of Pediatric Dentistry (AAPD) members in active private
      practice in the six New England States of Connecticut, Massachusetts, Maine, New
      Hampshire, Rhode Island, and Vermont. A self-addressed, stamped envelope was
      provided to facilitate the returned response. RESULTS: The survey had a response
      rate of 70%. Most practitioners (93%) routinely recommended dental prophylaxis
      for their recall patients. The proportion of practitioners who considered the
      following indications for recommending dental prophylaxis was: plaque, stain,
      and/or calculus removal - 99%; caries prevention - 75%; prior to topical fluoride
      application - 82%; prior to sealant application - 58%; and for behavioral
      modification - 68%. Almost two thirds of the practitioners (62%) defined dental
      prophylaxis as referring to both rubber cup pumice prophylaxis as well as to
      toothbrush prophylaxis. However, only one in four practitioners (26%) had
      modified her/his clinical practice to substitute toothbrush prophylaxis in lieu
      of rubber cup pumice prophylaxis. CONCLUSION: Pediatric dentists in New England
      routinely provide dental prophylaxis to their recall patients.

PMID- 15558087
TI  - The comparison of various oral hygiene strategies in neuromuscularly disabled
      individuals.
AB  - BACKGROUND: This study aims to investigate the effect of various oral hygiene
      strategies on the symptoms of inflammation in neuromuscularly disabled patients
      and to define the optimum hygiene method. METHODS: Fifty-nine neuromuscularly
      disabled participants, suffering from cerebral palsy, were randomly divided into
      five groups as follows: Group M: manual toothbrush (n=14), Group E: electrically
      powered toothbrush (n=9), Group MC: manual toothbrush and chlorhexidine gluconate
      (CHX) spray (n=13), Group EC: electrically powered toothbrush and CHX spray
      (n=9), and Group C: CHX spray (n=14). The oral hygiene applications were provided
      by the parents and staff. At baseline and after 21 days the plaque index (PI),
      the gingival index (GI), and bleeding on probing (BOP) were recorded. RESULTS: In
      intra-group comparisons of the pre- and post-application scores, in all groups
      the PI and GI scores and BOP percentages, except in Group C, were found
      significantly different (p<0.05). There were significant differences among the
      post-application scores, between Group M and Group E and between Group C and
      Group E in PI scores; between Group C and Group E the difference in GI scores
      were found statistically significant (p<0.05). CONCLUSIONS: Although all oral
      hygiene strategies reduced plaque and gingival inflammation, the results of our
      study suggested the electrically powered toothbrush could be more recommendable
      to neuromuscularly disabled people in these strategies, while the combined
      procedures appeared to be neither beneficial nor favorable.

PMID- 15558088
TI  - Flowable composites as "filled adhesives:" a microleakage study.
AB  - OBJECTIVE: The purpose of this in vitro study was to investigate the microleakage
      at dentin margins of a flowable resin composite associated with an adhesive,
      either light cured separately or co-cured, in Class V cavities. MATERIALS AND
      METHODS: Twenty four recently extracted human molars were prepared with
      standardized box-shaped Class V cavities of 3.0 mm (mesial-distal), 2.0 mm
      (occlusal-gingival), and 2.0 mm depth with margins located on enamel and
      dentin/cementum on the buccal or lingual surfaces. The cavities were randomly
      assigned into three groups (n=8): Group I - Single Bond + Filtek Z250 (control);
      Group II - Single Bond + Filtek Flow (light cured separately) + Filtek Z250; and
      Group III - Single Bond + Filtek Flow co-cured (light cured simultaneously) +
      Filtek Z250. After being immersed in tap water for 24 h, the specimens were
      thermocycled (1000x, 5 degrees -55 degrees C, 30 sec dwell time) and immersed in
      a 0.5% basic fuchsine solution for 24 h. The restorations were sectioned
      longitudinally and gingival margins were evaluated for microleakage using a 0-4
      scale. Data were subjected to the Kruskal-Wallis test at p<0.05. RESULTS: A
      statistically significant difference at p = 0.0044 between Groups 1 and 3 and
      Groups 2 and 3 was observed. Although Group 2 performed slightly better than
      Group 1, no significant difference was observed. CONCLUSION: The use of a
      flowable resin composite cured simultaneously with an adhesive yielded the worst
      results in this study. As no statistical differences were seen between Groups 1
      and 2, the use of a flowable composite as a means of minimizing microleakage at
      dentin margins may be questioned.

PMID- 15558089
TI  - Surface hardness properties of resin-modified glass ionomer cements and polyacid
      modified composite resins.
AB  - In this study the top and bottom surface hardness of two polyacid-modified
      composite resins (PMCRs), one resin-modified glass ionomer cement (RMGIC), and
      one composite resin were evaluated. The affect of water storage on their hardness
      was also investigated. The study was conducted using four different groups, each
      having five specimens obtained from fiberglass die molds with a diameter of 5 mm
      and a height of 2 mm. Measurements were made on the top and bottom surface of
      each specimen and recorded after 24 hours and again at 60 days. All tested
      materials showed different hardness values, and the values of top surfaces of the
      specimens were found to be higher than the bottom surface in all test groups.
      There was no statistical difference in the Vickers hardness (HV) values when the
      test specimens were kept in water storage. In conclusion Hytac displayed
      microhardness values higher than Vitremer and Dyract. We found the order of HV
      values to be Surfil > Hytac > Dyract > Vitremer, respectively. Vitremer presented
      the lowest microhardness level and Surfil the highest.

PMID- 15558090
TI  - An in vivo evaluation of the diagnostic quality ultra-speed versus insight
      intraoral dental film.
AB  - Twelve sets of FMS (full mouth survey) radiographs were taken by California
      licensed radiology technicians. Ten of the sets of FMS radiographs were taken
      using Ultra-Speed "D" film on the left side of the patient and Insight "F" speed
      film on the right side of the patient. The remaining two sets of films were taken
      using Insight Film on both sides of the patient to act as a control. Ten faculty
      members of the Diagnostic Department were asked to evaluate the twelve sets of
      FMS radiographs and report whether they had a preference for the right side, left
      side, or no preference. Criteria for preference were diagnostic ability and
      clarity of the films. The results of the study showed a preference for the right
      side (65.7%), which was imaged with Insight Film, compared to the left side
      (34.3%), which was imaged with Ultra-Speed Film.

PMID- 15558091
TI  - Evaluation of the diagnostic advantage of intraoral D and E film for detecting
      interproximal caries.
AB  - Clinicians strive to reduce the exposure of patients to X-ray radiation in an
      effort to decrease its harmful effects on the body. A potential strategy for
      achieving this goal is the use of high-speed films that require less exposure to
      radiation to generate a diagnostic image. There are two film types commonly used
      in intraoral radiography: high speed or "Ekta-speed" film (Type E) and normal
      speed or Ultra-speed film (Type D). Type E film requires nearly half of the
      exposure time that is required by Type D films to produce an acceptable
      diagnostic image; however, the diagnosis quality and usability of these film
      types are under question. The purpose of this research is to compare the
      diagnostic quality of Type E with Type D film when used to diagnose proximal
      caries. In this study 40 pairs of extracted maxillary premolar teeth were chosen
      and divided into four groups of 10 pairs. Cavities were made on proximal surfaces
      at different depths (0.5, 1, 1.5, and 2 mm) for each group. Bitewing radiographs
      were then taken on each pair of teeth using Type E film and then again using Type
      D film. Radiographs were evaluated by two oral radiologists and two operative
      dentistry specialists who recorded the perceived diagnostic depth of the prepared
      cavities. Our data showed both Type D and E films are suitable for use in
      diagnosing proximal caries, and despite a minor discrepancy between them no
      significant difference was found with regard to their value in diagnosing
      proximal caries.

PMID- 15558092
TI  - The pH changes of four different root canal sealers after mixing at various time
      intervals in vitro.
AB  - The purpose of this study was to compare the surface pH level of four different
      type sealers after mixing at various time intervals in vitro. After cleaning and
      shaping root canals in 50 recently extracted, single-rooted human teeth, they
      were divided into six groups. Each of four groups was obturated with Apexit, N2,
      Sealapex, and Grossman sealers. The remaining groups served as controls. In group
      1 nothing was added to the vial of saline solution. In group 2 canals had been
      instrumented but not obturated with sealer. The pH level of saline solutions was
      determined at intervals of 1 hour, 4 hours, 1 day, 2 days, 3 days, 1 week, and 4
      weeks after teeth were placed in them. The pH levels of the five solutions were
      compared to each other and to that of saline solution only.

PMID- 15558093
TI  - Nickel and cobalt hypersensitivity reaction before and after orthodontic therapy
      in children.
AB  - Nickel and cobalt are major components of alloys used in orthodontics. The
      objectives of this cross-sectional study was to determine the prevalence of a
      nickel hypersensitivity reaction before and after orthodontic treatment with
      conventional stainless steel brackets and wires. The total sample consisted of 82
      patients (55 females, and 27 males) from the Orthodontic Department at the
      Faculty of Dentistry, Suleyman Demirel University. A patch test and a
      questionnaire were used to evaluate hypersensitivity to these metals. The
      statistical analysis was carried out using Fisher's exact X(2) (2 x 2) test. The
      prevalence of nickel allergy was found to be higher in females than males (14.55%
      in females, 0% in males), and the prevalence of cobalt allergy was found to be
      9.76% (7.27% in females, 14.81% in males). Orthodontic treatment with
      conventional stainless steel alloys does not appear to have an allergenic effect
      on the gingival and oral health of the patient. A family history of an allergy to
      these metals or the use of metallic objects in contact with the skin do not
      characterize nickel and cobalt hypersensitivity. This suggests orthodontic
      therapy with conventional stainless steel appliances does not initiate or
      aggravate a nickel hypersensitivity reaction. There was no association between
      the before treatment and after treatment to a nickel and cobalt hypersensitivity
      reaction.

PMID- 15558094
TI  - Qualitative and quantitative analysis of bacterial aerosols.
AB  - The objective of this study was to investigate qualitatively and quantitatively
      the bacterial aerosols before, during, and after clinical work sessions in
      different areas within a multichair dental clinic, an isolation clinic, the
      sterilization center, and the prosthetic laboratory in the College of Dentistry,
      King Saud University. Also, the contributions of aerosols generated by different
      types of dental procedures were investigated. Air sampling using blood and heart
      infusion agar plates at four selected areas was performed three times per day
      over a 2-week period before, during, and after clinical sessions. The
      concentration of total bacterial aerosols was 5 times higher in the multichair
      clinic, 3.6 times higher in the prosthetic laboratory, 2 times higher in the
      sterilization center and isolation clinic during working sessions as compared to
      before the working sessions. At the end of the working day, aerosols decreased 50
      70% in all areas. Staphylococcus epidermidis had the highest prevalence (37.12q%)
      of colony composition of bacteria examined. This study demonstrates that aerosols
      increase during and after work sessions and, therefore, increase the chance for
      infectious agent transmission. Preventive measures should be instituted to reduce
      or disrupt aerosols as a transmission route in the multichair dental clinic,
      sterilization center, prosthetic laboratory, and isolation clinic.

PMID- 15558095
TI  - The evolving impact of aging America on dental practice.
AB  - American dentistry has recognized for a quarter century that the growth in the
      proportion of elderly in the population is impacting on the profession. Multiple
      articles in the professional literature have speculated on the ways in which this
      change will be manifested. Data and projections from earlier articles are
      revisited and five trends are offered to guide professionals as they position
      their practices for the coming years. The increase in number and proportion of
      elderly in dental practices stems from successes in preventing and controlling
      infectious diseases during the last century. The trend has not peaked but will
      continue for at least two more decades. Retention of teeth into advanced age has
      resulted from emerging and improved preventive and restorative dental advances
      directed at children and adults beginning mid-century, and dental utilization
      studies confirm the elderly are seeking dental care at an unprecedented and
      growing rate. Chronic disease and infirmity that accompany advanced age make
      dental care more challenging for this group. Dentists and their staff will need
      to continuously undertake educational opportunities that will foster and maintain
      their facility in providing care to the elderly. They will need to do this
      because Americans of advanced age are becoming the dominant age group seeking,
      and able to pay for, sophisticated dental services. The blend of those services
      is shifting away from removable prostheses to a rising demand for restorative,
      periodontic, and endodontic care. Root caries, in particular, will be a growing
      challenge to both providers and patients. There is mounting evidence oral disease
      impacts endocrine, cardiovascular, and pulmonary health, particularly in frail
      elders, and will likely provide many elderly additional stimuli to seek dental
      care. Providers who seek an alternative approach for delivering their services
      will find growing demand for and satisfaction with traveling to patients, rather
      than the other way around.

PMID- 15558096
TI  - Fixed prosthetics with a connective tissue and alloplastic bone graft ridge
      augmentation: a case report.
AB  - Augmentation of the partially edentulous ridge can significantly improve the
      final prosthodontic rehabilitation. For enhancing soft tissue contours in the
      anterior region, the subepithelial connective tissue graft is the treatment of
      choice. The combination of connective tissue grafts with alloplastic bone graft
      material can optimize the ridge augmentation and reduce post extraction defects.
      The aim of this clinical report is to describe the use of subepithelial
      connective tissue in conjunction with an alloplastic bone graft for augmentation
      of a maxillary anterior ridge prior to prosthetic rehabilitation.

PMID- 15558097
TI  - Labial veneers in the management of desquamative gingivitis: report of a case.
AB  - Desquamative gingivitis is a condition characterized by intense erythema,
      ulceration, and desquamation of the free and attached gingiva. Approximately 50%
      of desquamative gingivitis cases occur on the gingival tissues though it is not
      uncommon at other intraoral and extraoral sites. Though topical corticosteroids
      are considered the mainstays in the treatment of desquamative gingivitis, the
      inability of these medicaments to be in contact with the affected sites for
      longer duration has been implicated as a factor in reducing the efficacy of this
      mode of treatment. The case presented here is of a 24-year old male with
      desquamative gingivitis of 3 years duration. Topical corticosteroid therapy using
      custom-made acrylic veneers was utilized in the patient with remarkable results.
      This paper highlights the use of acrylic labial veneers over the gingival tissue
      as a vehicle for delivering medication and as a way to improve aesthetics.

PMID- 15558098
TI  - Treatment of xerostomia in prosthetic patients using local acupuncture points on
      the face.
AB  - Acupuncture is gaining popularity in mainstream dentistry to treat various
      conditions. This paper aims to present acupuncture techniques to treat prosthetic
      patients with xerostomia using local acupuncture points on the face.

PMID- 15558099
TI  - Multiple dentoalveolar traumatic lesions: report of a case and proposition of
      dental polytrauma as a new term.
AB  - Traumatic injuries to permanent teeth are common, and dramatic episodes can occur
      during childhood. The aim of this paper is to present a report of severe trauma
      to the orofacial complex of an 8-year old girl that resulted in multiple
      injuries. The use of the term "dental polytrauma" (concomitant different dental
      traumatic injuries) is advocated in this case presentation.

PMID- 15558100
TI  - An unusual foreign body (suturing needle) in the tonsillar region.
AB  - This case report describes the presence of a foreign body (surgical needle) in
      the tonsillar area. The needle was overlooked during surgery. Following the
      surgery, the patient had no pain or other complaints related to the surgical
      site. There are only a few reported cases of forgotten surgical materials in
      operation sites in the literature.

PMID- 15558101
TI  - Wireless networking for the dental office: current wireless standards and
      security protocols.
AB  - Digital radiography has gained immense popularity in dentistry today in spite of
      the early difficulty for the profession to embrace the technology. The transition
      from film to digital has been happening at a faster pace in the fields of
      Orthodontics, Oral Surgery, Endodontics, Periodontics, and other specialties
      where the radiographic images (periapical, bitewing, panoramic, cephalometric,
      and skull radiographs) are being acquired digitally, stored within a server
      locally, and eventually accessed for diagnostic purposes, along with the rest of
      the patient data via the patient management software (PMS). A review of the
      literature shows the diagnostic performance of digital radiography is at least
      comparable to or even better than that of conventional radiography. Similarly,
      other digital diagnostic tools like caries detectors, cephalometric analysis
      software, and digital scanners were used for many years for the diagnosis and
      treatment planning purposes. The introduction of wireless charged-coupled device
      (CCD) sensors in early 2004 (Schick Technologies, Long Island City, NY) has moved
      digital radiography a step further into the wireless era. As with any emerging
      technology, there are concerns that should be looked into before adapting to the
      wireless environment. Foremost is the network security involved in the
      installation and usage of these wireless networks. This article deals with the
      existing standards and choices in wireless technologies that are available for
      implementation within a contemporary dental office. The network security
      protocols that protect the patient data and boost the efficiency of modern day
      dental clinics are enumerated.

PMID- 15558102
TI  - AAOMP case challenge: a nodular lesion of the tongue.

PMID- 15558106
TI  - [Morbidity following cardiac surgery. A proposal for qualification].
AB  - The authors propose a new scoring table to quantify morbidity events related to
      cardiac surgery. They intend to quantify the relative impact of each occurred
      event and also to calculate and score the sum of all morbidity events occurring
      in a given patient. The table was constructed based on the opinion of a panel of
      international experts that were asked to quantify the morbidity events on the
      proposed list. Their answers were integrated and analyzed according to the
      inferring Delphi's method, in order to establish the relative weight of each
      event, scoring events for each system. The methodology that was adopted is
      throughly discussed and speculation is made over the use of the table score for
      related morbidity in cardiac surgery, namely as a tool to compare both the
      surgical performance and for quality ranking. The scoring table is now being
      tested clinically.

PMID- 15558107
TI  - [Video-assisted thoracic surgery in the diagnosis of interstitial diffuse
      pulmonary diseases].
AB  - Interstitial lung diseases are best diagnosed by surgical lung biopsy.
      Videoassisted thoracoscopy (VATS) is less aggressive than open lung thoracotomy
      and its development is associated with an increased number of lung biopsies.
      Between July 1994 and July 2004 we performed 70 VATS biopsies for interstitial
      lung disease patients. Only one biopsy was considered inconclusive (1.4%). The
      remainder 69 (98.6%) established a final diagnosis. The results in our series
      show that VATS lung biopsy is a safe method with low mortality and morbidity and
      an excellent rentability.

PMID- 15558108
TI  - [Egas Moniz and the obstructions of the internal carotid artery].
AB  - Claude Miller Fisher is quoted as the discoverer of the pathogenic relationship
      between the carotid artery occlusive disease and cerebral ischemia, through his
      work published in 1951, where he describes the cerebral consequences arising from
      the internal carotid artery occlusion and, later on, the diverse clinical
      manifestations that it can cause (TIA's and CVA's). However, 20 years before,
      Egas Moniz, following the research work which lead to the discovery of cerebral
      angiography, had already mentioned and demonstrated such relationship, and
      published their observations in the portuguese, spanish and french medical
      literatures. As he did not published his works in the english literature, he did
      not get credit nor recognition on the fact, that was later developed by Miller
      Fisher who dedicated extensive contribution and divulgation on the subject. The
      present paper is dedicated to an historical review of the pionier work of Egas
      Moniz and co-workers, aimed to a better understanding of the pathogenic
      relationship between internal carotid artery occlusions and cerebral ischemia.

PMID- 15558109
TI  - Are the vasodilators needed in critical limb ischemia? Laser Doppler flowmetry
      study.
AB  - Twenty patients with critical limb ischemia, fulfilling the criteria of European
      Consensus of Critical Limb Ischemia, were included in the study. Fifteen healthy
      subjects served as the controls. Laser Doppler flowmetry method was applied to
      assess the peripheral skin microcirculation during provocation tests such as
      transcutaneous electrical nerve stimulation and veno-arterial reflex. In
      physiological conditions transcutaneous electrical nerve stimulation evokes short
      term, reversible increase of cutaneous blood flow during stimulation. Veno
      arterial reflex is defined as an increase of precapillary resistance while
      standing or lowering of the extremity, mirrored by the reduction of skin
      perfusion. The results of the study justify the thesis, that the vasodilators may
      not be effective in the treatment of critical limb ischemia. Further trials
      directly assessing the influence of vasodilatating agents on microcirculation in
      critical limb ischemia are required.

PMID- 15558110
TI  - [Eversion carotid endarterectomy].
AB  - It is widely accepted and proved the role of carotid endarterectomy in the
      prevention of cerebrovascular insufficiency. Some mater of controversy lies,
      presently, apart the role of the endovascular treatment, in the techniques of
      choice for the endarterectomy, as well as in the method employed for the
      arteriotomy closure. The authors report their experience with the eversion
      endarterectomy technique, discussing the results and enhancing the main
      indications of this alternative method for carotid endarterectomy.

PMID- 15558111
TI  - [Valvular transposition in patients with ulcers of the lower limbs following post
      thrombotic syndromes].
AB  - Venous ulcers in patients with post thrombotic syndromes are complex situations
      with multiple therapeutic options. They are responsible for high morbidity rates,
      conservative treatment is very slow and recurrences are very common. Deep venous
      reconstructive surgery is an alternative, but it should be based on the
      morphologic and functional aspects of the venous system and only adopted after a
      very careful study, including venography. The authors describe a morphological
      "pattern", found in some of these patients and related to the competence of the
      saphenous femoral junction, rendering possible to perform a valvular
      transposition. Seven patients with post thrombotic ulcers who have been treated
      during the last 6 years in which the pattern already described was detect,
      underwent a transposition of the superficial femoral vein, to the great saphenous
      vein and when necessary complemented with skyn grafts. Before the operation all
      patients had ulcers with more than 3 cm in size (3.2-5.4 cm) and with more than 4
      months duration (4-16 months). All ulcers healed in the postoperative period
      (mean time 28 days). All patients have been reevaluated in 2003 and it was
      diagnosed the thrombosis of two procedures, one of them with the recurrence of
      the ulcer who healed with conservative treatment. The authors consider this
      method as a very easy technique to perform, although rarely used, and a valid
      alternative in a highly selected group of patients.

PMID- 15558112
TI  - [Inflammatory aneurysms of the abdominal aorta, complicated by hydronephrosis and
      anuria. Surgical management].
AB  - In this paper the clinical condition of two male patients, aged 58 and 65 years
      are presented, after being admitted as a consequence of a rare complication of an
      inflammatory aneurysm of the abdominal aorta, which is an ureteral compression,
      with hydronephrosis, anuria and acute renal failure. After having an urgent
      haemodialysis session, the etiology of the process was diagnosed by echography
      and abdominal CT-scans, followed by ureteral catheterization, restoration of
      diuresis and normalization of renal function. Conventional surgery was performed
      later, in elective conditions, and the post operative course was normal, without
      complications. The main features of this clinical entity, its diagnosis and
      multidisciplinary management are presented and discussed.

PMID- 15558113
TI  - [Compartment syndrome].
AB  - The compartment syndrome is a common and severe clinical condition within the
      scope of peripheral vascular surgery and it is accompanied by a high risk of a
      limb loss or even the patients' death. Its etiology is linked to the acute limb
      ischemia or trauma and its management consists essentially in the descompressive
      fasciotomies, associated to diverse pharmacological agents with doubtful
      efficacy. The main features of this clinical entity and the criteria for
      therapeutic interventions are subjected to analysis and discussion.

PMID- 15558114
TI  - [Adult's aortic coarctation and congestive heart failure].

PMID- 15558115
TI  - Hydroalumination reactions on acetylenes and nitriles in the synthesis of
      carbaalanes and imidoalanes: an overview.
AB  - Hydroalumination reactions play an important role in industry as well as from the
      point of view of academics. The area of carbaalane chemistry is in its infant
      stage whereas aluminium nitride chemistry has generated a lot of interest from
      the synthetic and material science perspective. In this overview, we address the
      simple way of carrying out the hydroalumination reactions on acetylenes and
      nitriles in the synthesis of carbaalane and imidoalane cluster compounds. A
      possible mechanism involved in the synthesis of these compounds is discussed.
      Heteronuclear carbaalane and imidoalane clusters containing transition metals
      have also been emphasized.

PMID- 15558116
TI  - Ferromagnetic coupling and thermochromism in [Ni(rac-CTH)(mu1,1-N3)2Cu(N3)2], the
      first end-on azido-bridged bimetallic complex.
AB  - Reaction of [Ni(rac-CTH)(ClO(4))(2)](rac-CTH = rac-5,7,7,12,14,14-hexamethyl
      1,4,8,11-tetraazacyclotetradecane) with NaN(3) and Cu(NO(3))(2).3H(2)O produces
      the binuclear complex [Ni(rac-CTH)(mu(1,1)-N(3))(2)Cu(N(3))(2)] 1, which
      represents the first example of an end-on bridged bimetallic complex; 1 exhibits
      intramolecular ferromagnetic exchange coupling and thermochromism, this latter
      being a consequence of the intermolecular interaction at low temperature.

PMID- 15558117
TI  - Arrested chloride abstraction from trans-RuCl2(DMeOPrPE)2 with TlPF6; formation
      of a 1-D coordination polymer having unusual octahedral coordination around
      thallium(I).
AB  - An "arrested" chloride abstraction occurs in the reaction of trans
      RuCl(2)(DMeOPrPE)(2) with TlPF(6); the product is a 1-D coordination polymer in
      which the Tl(I) centers have an unusual octahedral coordination geometry with a
      stereochemically active 6s(2) lone pair.

PMID- 15558118
TI  - Assessment of intercomponent interaction in phenylene bridged dinuclear
      ruthenium(II) and osmium(II) polypyridyl complexes.
AB  - The synthesis and characterisation of [Ru(bipy)(2)(L1)](2+) and the homodinuclear
      complexes [M(bipy)(2)(L1)M(bipy)(2)](4+)(where M = Ru or Os), employing the
      ditopic ligand, 1,4-phenylene-bis(1-pyridin-2-ylimidazo[1,5-a]pyridine)(L1), are
      reported. The complexes are identified by elemental analysis, UV/Vis, emission,
      resonance Raman, transient resonance Raman and (1)H NMR spectroscopy, mass
      spectrometry and electrochemistry. The X-ray structure of the complex
      [Ru(bipy)(2)(L1)(bipy)(2)Ru](PF(6))(4) is also reported. DFT calculations,
      carried out to model the electronic properties of the compounds, are in good
      agreement with experiment. Minimal communication between the metal centres is
      observed. The low level of ground state electronic interaction is rationalized in
      terms of the poor ability of the phenyl spacer in facilitating superexchange
      interactions. Using the electronic and electrochemical data a detailed picture of
      the electronic properties of the RuRu compound is presented.

PMID- 15558119
TI  - A cautionary warning on the use of electrochemical measurements to calculate
      comproportionation constants for mixed-valence compounds.
AB  - The redox potentials for successive oxidations in a series of ligand-bridged
      dinuclear ruthenium complexes are shown to be dependent on the identity of the
      anion used as the electrolyte in the electrochemical measurements. Since the
      differences between these redox potentials (DeltaE(ox)) are often used to
      calculate the comproportionation equilibrium constants (K(c)) in mixed-valence
      species--and therefore the extent of inter-metal communication between the metal
      centres--the results demonstrate the need for extreme care in comparison of
      DeltaE(ox) data and of K(c) values derived from them.

PMID- 15558120
TI  - Solid-state spectroscopic properties and the geometry of binuclear rhodium(I)
      diisocyanoalkane complexes.
AB  - A series of crystalline dinuclear rhodium complexes with different bridging
      diisocyano ligands and different counter ions have been studied by low
      temperature crystallographic and solid-state spectroscopic techniques. The Rh-Rh
      distances vary from 4.5153(3) to 3.0988(7) angstroms, and the twist angles around
      the Rh-Rh line from 58.3(1) to 0 degree, both depending on the size and
      conformational rigidity of the bridging ligand. For very long distances as occur
      in the [Rh(2)(dimen)(4)](2+) salts the absorption is significantly blue-shifted
      compared to other complexes. For a given cation a shorter Rh-Rh bond gives a red
      shift of the phosphorescence emission band, indicating a smaller energy gap
      between the ground and emitting excited states. An exception occurs for the
      [Rh(2)(1,6-diisocyanohexane)(4)](2+) ion, in which dimer formation in the
      calixarate salt lengthens the Rh-Rh intramolecular bond length without affecting
      the emission spectrum.

PMID- 15558121
TI  - Titanium and niobium imido complexes stabilized by heteroscorpionate ligands.
AB  - The reaction of [Ti(NR)Cl(2)(py)(3)](R = (t)Bu, p-tolyl, 2,6-C(6)H(3)(i)Pr(2))
      with [{Li(bdmpza)(H(2)O)}(4)][bdmpza = bis(3,5-dimethylpyrazol-1-yl)acetate] and
      [{Li(bdmpzdta)(H(2)O)}(4)][bdmpzdta = bis(3,5-dimethylpyrazol-1-yl)dithioacetate]
      affords the corresponding complexes [Ti(NR)Cl(kappa(3)-bdmpzx)(py)](x = a, R =
      (t)Bu 1, p-tolyl 2, 2,6-C(6)H(3)(i)Pr(2) 3; x = dta, R =(t)Bu 4, p-tolyl , 2,6
      C(6)H(3)(i)Pr(2) 6), which are the first examples of imido Group 4 complexes
      stabilized by heteroscorpionate ligands. The solid-state X-ray crystal structure
      of 1 has been determined. The titanium centre is six-coordinate with three fac
      sites occupied by the heteroscorpionate ligand and the remainder of the
      coordination sphere being completed by chloride, imido and pyridine ligands. The
      complexes are 1-6 fluxional at room temperature. The pyridine ortho- and meta
      proton resonances show evidence of dynamic behaviour for this ligand and variable
      temperature NMR studies were carried out in order to study their dynamic
      behaviour in solution. The complexes [Nb(NR)Cl(3)(py)(2)](R = (t)Bu, p-tolyl, 2,6
      C(6)H(3)(i)Pr(2)) reacted with [{Li(bdmpza)(H(2)O)}(4)] and (Hbdmpze)[bdmpze =
      2,2-bis(3,5-dimethylpyrazol-1-yl)ethoxide], the latter with prior addition of
      (n)BuLi, to give the complexes [Nb(NR)Cl(2)(kappa(3)-bdmpzx)](x = a, R =(t)Bu 7,
      p-tolyl 8, 2,6-C(6)H(3)(i)Pr(2) 9; x = e, R = (t)Bu 10, p-tolyl 11, 2,6
      C(6)H(3)(i)Pr(2)) 12 and these are the first examples of imido Group 5 complexes
      with heteroscorpionate ligands. The structures of these complexes have been
      determined by spectroscopic methods.

PMID- 15558123
TI  - Reaction of [M(eta3-allyl)(eta2-amidinato)(CO)2(pyridine)] complexes (M = Mo, W)
      with bidentate ligands: nitrogen donor vs. phosphorus donor.
AB  - The reactivity of amidinato complexes of molybdenum and tungsten bearing pyridine
      as a labile ligand, [M(eta(3)-allyl)(eta(2)-amidinato)(CO)(2)(pyridine)](M = Mo;
      1-Mo, M = W; 1-W), toward bidentate ligands such as 1,10-phenanthroline (phen)
      and 1,2-bis(diphenylphosphino)ethane (dppe) was investigated. The reaction of 1
      with phen at ambient temperature resulted in the formation of monodentate
      amidinato complexes, [M(eta(3)-allyl)(eta(1)-amidinato)(CO)(2)(eta(2)-phen)](M =
      Mo; 2-Mo, M = W; 2-W), which has pseudo-octahedral geometry with the amidinato
      ligand coordinated to the metal in an eta(1)-fashion. The phen ligand was located
      coplanar with two CO ligands and the eta(1)-amidinato ligand was positioned trans
      to the eta(3)-allyl ligand. In solution, both complexes 2-Mo and 2-W showed
      fluxionality, and complex 2-Mo afforded allylamidine (3) on heating in solution.
      In the reaction of 1 with dppe at ambient temperature, the simple substitution
      reaction took place to give dppe-bridged binuclear complexes [{M(eta(3)
      allyl)(eta(2)-amidinato)(CO)(2)}(2)(mu-dppe)](M = Mo; 5-Mo, M = W; 5-W), whereas
      mononuclear monocarbonyl complexes [M(eta(3)-allyl)(eta(2)-amidinato)(CO)(eta(2)
      dppe)](M = Mo; 6-Mo, M = W; 6-W) were obtained under acetonitrile- or toluene
      refluxing conditions. Mononuclear complex 6 was also obtained by the reaction of
      binuclear complex 5 with 0.5 equivalents of dppe under refluxing in acetonitrile
      or in toluene. The X-ray analyses and variable-temperature (31)P NMR spectroscopy
      of complex 6 indicated the existence of the rotational isomers of the eta(3)
      allyl ligand, i.e., endo and exo forms, with respect to the carbonyl ligand. The
      different reactivity of complex 1 toward phen and dppe seems to have come from
      the difference in the pi-acceptability of each bidentate ligand.

PMID- 15558122
TI  - Mono- and binuclear cyclometallated palladium(II) complexes containing bridging
      (N,O-) and terminal (N-) imidate ligands: air stable, thermally robust and
      recyclable catalysts for cross-coupling processes.
AB  - Novel dinuclear cyclometallated palladium complexes [{Pd(mu-NCO)(C circumflex
      accent N)}(2)], containing asymmetric imidato -NCO- bridging units have been
      synthesised [C circumflex accent N = 7,8-benzoquinolyl; -NCO- = succinimidate
      (1c), phthalimidate (1a-3a) or maleimidate (3c)]. The reaction of these
      complexes, and the previously reported analogous imidate precursors containing a
      phenylazophenyl (1a-3a) or 2-pyridylphenyl (1b-3b) backbone, with tertiary
      phosphines provides novel mononuclear N-bonded imidate derivatives of the general
      formula [Pd(C circumflex accent N)(imidate)(L)][L = PPh(3), P(4-F-C(6)H(4))(3) or
      P(4-MeO-C(6)H(4))(3)]. The single crystal structures of
      [Pd(azb)(phthalimidate)(P(4-MeO-C(6)H(4))(3))](9a) and
      [Pd(bzq)(phthalimidate)(PPh(3))](7c) have been established. Dinuclear complexes
      (1a-3a, 1b-3b, 1c-3c) demonstrate outstanding thermal stability in the solid
      state, as shown by thermoanalytical techniques. A marked influence of bridging
      imidate groups on the initial decomposition temperature is observed. The
      dinuclear and mononuclear derivatives are shown to be active
      catalysts/precatalysts for the Suzuki-Miyaura cross-coupling reactions of aryl
      bromides with aryl boronic acids, and the Sonogashira reactions of aryl halides
      with phenyl acetylene (in the presence and absence of Cu(I) salts). The
      conversions appear to be dependent, to some extent, on the type of imidate
      ligand, suggesting a role for these pseudohalides in the catalytic cycle in both
      cross-coupling processes. Lower catalyst loadings in 'copper-free' Sonogashira
      cross-couplings favour higher turnover frequencies. We have further determined
      that these catalysts may be recycled using a poly(ethylene oxide)(PEO)/methanol
      solvent medium in Suzuki-Miyaura cross-coupling. Once the reaction is complete,
      product extraction into a hexane/diethyl ether mixture (1 : 1, v/v) gives cross
      coupled products in good yields (with purity > 95%). The polar phase can then be
      re-used several times without appreciable loss of catalytic activity.

PMID- 15558124
TI  - Protonation and H/D exchange reactions promoted by a sulfur-rich osmium hydride
      complex: identification of a labile dihydrogen complex.
AB  - The sulfur-rich osmium nitrosyl complexes Bu(4)N[Os(NO)((bu)S(2))(2)] (1)
      [(bu)S(2)(2-) = 3,5-tert-butyl-1,2-benzenedithiolate(2-)] and
      [Os(NO)(py(bu)S(4))]Br ()[py(bu)S(4)(2-) = 2,6-bis(2-sulfanyl-3,5-di-tert
      butylphenylthio)dimethylpyridine(2-)] have been synthesized. The molecular
      structure of 1 exhibits a square-pyramidal geometry with the NO group at the
      apical position. A pseudo-octahedral geometry with two thiolate and two thioether
      donors in trans configuration is found for 2. Compound 2 shows two quasi
      reversible one-electron redox waves at E(1/2) = 0.51 and -0.46 V vs. NHE for the
      redox couples [Os(NO)(py(bu)S(4))](+1/0) and [Os(NO)(py(bu)S(4))](0/-1),
      respectively. 2 reacts with NaAlH(4) to produce Na[Os(H)(py(bu)S(4))] (3), which
      exhibits a typical hydride resonance in the (1)H NMR spectrum at delta =-15.03
      ppm. Protonation of 3 with HBF(4)/CD(3)OD at 20 degrees C rapidly releases
      H(2)/HD to afford the dinuclear complex [Os(py(bu)S(4))](2) (4). Low temperature
      (1)H and (2)H NMR spectra of in [D(8)]THF with CH(3)OH or CD(3)OD at -80 degree C
      allow the observation of the formation of [Os(H(2)/HD)(py(bu)S(4))]. A 1 : 1 : 1
      triplet at delta = -7.84 ppm [J(HD) = 31.2 Hz] and a relaxation time of T(1)(min)
      = 6 ms (-65 degrees C, 270 MHz) firmly establish the presence of eta(2)-H(2)/HD
      ligand. At room temperature, 3 interacts with D(2) (1 atm) and undergoes
      heterolytic D(2) cleavage followed by H/D exchange to form Na[Os(D)(py(bu)S(4))]
      (3a). A plausible cyclic mechanism has been proposed.

PMID- 15558125
TI  - Mono-, di- and trinuclear 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tppz)-containing
      copper(II) complexes: syntheses, crystal structures and magnetic properties.
AB  - Three new copper(ii) complexes of formula [Cu(tppz)(NCO)(2)].0.4H(2)O (1),
      [Cu(2)(tppz)Br(4)](2) and [Cu(3)(tppz)(C(5)O(5))(3)(H(2)O)(3)].7H(2)O (3)[tppz =
      2,3,5,6-tetrakis(2-pyridyl)pyrazine; C(5)O(5)(2-) = croconate, dianion of 4,5
      dihydroxycyclopent-4-ene-1,2,3-trione] have been synthesised and structurally
      characterized by X-ray diffraction methods. The structure of complex is made up
      of neutral [Cu(tppz)(NCO)(2)] mononuclear units and uncoordinated water
      molecules. The mononuclear units are grouped by pairs to give a rather short
      copper-copper distance of 3.9244(4) angstroms. The structure of complex 1
      consists of neutral tppz-bridged [Cu(2)(tppz)Br(4)] dinuclear units, the copper
      copper separation across tppz being 6.6198(1) angstroms. The dinuclear units are
      further connected through weak, double out-of-plane Cu-Br...Cu bridges
      [Br(1)...Cu(1a) 4.0028(17) angstroms] creating tetranuclear entities, the copper
      copper separation through this interaction being 4.3299(21) angstroms. The
      structure of complex 3 is built of neutral [Cu(3)(tppz)(C(5)O(5))(3)(H(2)O)(3)]
      trinuclear units and uncoordinated water molecules. Tppz and one of the croconate
      groups act as bridging ligands, the former exhibiting the bis-terdentate
      coordination mode and the latter adopting an unusual asymmetrical bis-bidentate
      bridging mode through three adjacent oxygen atoms. The other two croconate groups
      exhibit the bidentate coordination mode. The intramolecular copper-copper
      separations are 6.5417(9)(across tppz) and 4.3234(9) angstroms (through bis
      bidentate croconato). The magnetic properties of 2 and 3 have been investigated
      in the temperature range 1.9-300 K. The magnetic behaviour of complex 2 is that
      of an antiferromagnetically coupled copper(II) dimer (J = -40.9 cm(-1), the
      Hamiltonian being H = -JS(A).S(B)). In the case of compound , the chi(M) T vs. T
      plot is typical of an overall antiferromagnetic coupling with a low-lying spin
      doublet being fully populated at T < 10 K. The values of the intramolecular
      antiferromagnetic interactions in 3 are -19.9 (across tppz) and -32.9 cm(
      1)(through bridging croconato). Density functional type calculations were
      performed on model dinuclear fragments of 3 in order to analyze the efficiency of
      the exchange pathways involved and also to substantiate the coupling parameters.

PMID- 15558126
TI  - Preparation, electrochemical and spectral properties of N-methyl-pyridylethynyl
      nickel porphyrins.
AB  - A series of nickel N-methyl-pyridylethynylporphines were synthesized and their
      electrochemical and absorption properties were studied. UV-visible spectra of
      these complexes show that the absorption red-shifts of the nickel porphyrins are
      as significant as the zinc analogues. Although the reduction potential shifts
      caused by the electron-withdrawing substituents are not as large as the zinc
      complexes, the first reduction potentials of the nickel porphyrins are more
      positive than those of the zinc counterparts. In addition, the redox behaviors of
      these nickel porphyrins are similar to those of the zinc analogues.

PMID- 15558127
TI  - Gas phase oxidation of alkoxo ligands in bis(peroxo)[MO(O2)2(OR)]- and trisoxo
      [MO3(OR)]- anions (M = Cr, Mo, W).
AB  - The anions [M(VI)O(O(2))(2)(OR)](-) and [M(VI)O(3)(OR)](-)(M = Cr, Mo, W; R = H,
      Me, Et, (n)Pr, (i)Pr) were transferred to the gas phase by the electrospray
      process. Their decomposition was examined by multistage mass spectrometry and
      collisional activation experiments. The molybdate and tungstate anions
      [M(VI)O(O(2))(2)(OR)](-) underwent parallel elimination of aldehyde (ketone) and
      dioxygen while the equivalent chromate underwent loss of dioxygen only. The
      peroxo ligands were the source of oxidising equivalents in both reactions. For
      each alkoxo ligand, the total yield of aldehyde for the tungstate system exceeded
      that for the molybdate system. Collisional activation of [M(VI)O(3)(OMe)](-) led
      to clean elimination of formaldehyde with the metal centre supplying the
      oxidising equivalents. For larger alkoxo ligands, only the chromate centre
      eliminated aldehyde, while the molybdate and tungstate centres underwent clean
      loss of alkene. Threshold activation voltages indicated that the peroxo ligands
      of [W(VI)O(O(2))(2)(OMe)](-) are more oxidising than the tungstate centre of
      [W(VI)O(3)(OMe)](-). (2)H and (18)O isotope tracing experiments were consistent
      with a formal hydride transfer mechanism operating for oxidation of alkoxo ligand
      in each system. In the solid state, anions [M(VI)O(O(2))(2)(OR)](-) are typically
      pentagonal pyramidal (oxo in apical site) while [M(VI)O(3)(OR)](-) are
      tetrahedral. The data indicate that an equatorial ligand position is the site of
      alkoxo oxidation in [M(VI)O(O(2))(2)(OR)](-) anions. Comparisons of the gas phase
      data with those for a solution phase system are made.

PMID- 15558128
TI  - Tin(IV) halide complexes of AsPh3) The structures of trans-SnCl4(AsPh3)2 and
      SnBr4(AsPh3).AsPh3.
AB  - The structures of two 1 : 2 adducts between tin(IV) halides and AsPh(3) have been
      determined. SnCl(4)(AsPh(3))(2) adopts a six-coordinate geometry at tin in which
      the two organoarsine donors are mutually trans. In contrast, SnBr(4)(AsPh(3))(2)
      is five-coordinate at tin and only one arsine is directly bonded to the metal, in
      an axial site of the trigonal bipyramid. The second AsPh(3) group has a close
      contact with the axially bound bromine [As...Br: 3.567(3) angstroms], which is a
      unique structural variation that depicts an intermediate in a halogen-transfer
      reaction between Group 14 and Group 15 elements. AACVD using SnCl(4)(AsPh(3))(2)
      generates a film containing SnO(2) and a second crystalline material which is
      possibly SnCl(2), but which contains no arsenic.

PMID- 15558129
TI  - Synthesis, characterization, and electrochemical and electrochromic properties of
      sandwich dilutetium tetraphthalocyanine.
AB  - A new sandwich-tpype dilutetium tetraphthalocyanine 4 has been synthesized by the
      reaction of dimeric lutetium(III) phthalocyanine 3 with two equiv. of dilithium
      octakishexylthiophthalocyanine in amyl alcohol. Compound 3 was prepared from
      4',5',4",5"-tetraiminoisoindoline(1,4,7,10-tetrathia-12-crown-4) 1, 4,5
      bis(hexylthio)-1,2-diiminoisoindoline and lutetium acetate in amyl alcohol.
      Compounds 3 and 4 were characterized by elemental analysis, UV/visible, IR, (1)H
      NMR and ESR spectroscopy. The electrochemical and electrochromic properties of 3
      and 4 have been examined by cyclic voltammetry. Both 3 and 4 displayed well
      defined electrochromic behavior.

PMID- 15558130
TI  - Reactivity of the bis(pentafluorophenyl)boranes ClB(C6F5)2 and [HB(C6F5)2]n
      towards late transition metal reagents.
AB  - The reactivities of the highly electrophilic boranes ClB(C(6)F(5))(2) (1) and
      [HB(C(6)F(5))(2)](n) (2) towards a range of organometallic reagents featuring
      metals from Groups 7-10 have been investigated. Salt elimination chemistry is
      observed 1 between and the nucleophilic anions eta(5)-C(5)R(5))Fe(CO)(2)](-)(R =
      H or Me) and [Mn(CO)(5)](-), leading to the generation of the novel boryl
      complexes (eta(5)-C(5)R(5))Fe(CO)(2)B(C(6)F(5))(2)[R = H (3) or Me (4)] and
      (OC)(5)MnB(C(6)F(5))(2) (5). Such systems are designed to probe the extent to
      which the strongly sigma-donor boryl ligand can also act as a pi-acceptor; a
      variety of spectroscopic, structural and computational probes imply that even
      with such strongly electron withdrawing boryl substituents, the pi component of
      the metal-boron linkage is a relatively minor one. Similar reactivity is observed
      towards the hydridomanganese anion [(eta(5)-C(5)H(4)Me)Mn(CO)(2)H](-), generating
      a thermally labile product identified spectroscopically as (eta(5)
      C(5)H(4)Me)Mn(CO)(2)(H)B(C(6)F(5))(2) (6). Boranes 1 and 2 display different
      patterns of reactivity towards low-valent platinum and rhodium complexes than
      those demonstrated previously for less electrophilic reagents. Thus, reaction of
      1 with (Ph(3)P)(2)Pt(H(2)C=CH(2)) ultimately generates EtB(C(6)F(5))(2) (10) as
      the major boron-containing product, together with cis-(Ph(3)P)(2)PtCl(2) and
      trans-(Ph(3)P)(2)Pt(C(6)F(5))Cl (9). The cationic platinum hydride
      [(Ph(3)P)(3)PtH](+) is identified as an intermediate in the reaction pathway.
      Reaction of with [(Ph(3)P)(2)Rh(mu-Cl)](2), in toluene on the other hand, appears
      to proceed via ligand abstraction with both Ph(3)P.HB(C(6)F(5))(2) (11) and the
      arene rhodium(I) cation [(Ph(3)P)(2)Rh(eta(6)-C(6)H(5)Me)](+) (14) ultimately
      being formed.

PMID- 15558131
TI  - Vibrational spectroscopic force field studies of dimethyl sulfoxide and
      hexakis(dimethyl sulfoxide)scandium(III) iodide, and crystal and solution
      structure of the hexakis(dimethyl sulfoxide)scandium(III) ion.
AB  - Hexakis(dimethyl sulfoxide)scandium(III) iodide, [Sc(OS(CH(3))(2))(6)]I(3)
      contains centrosymmetric hexasolvated scandium(III) ions with an Sc-O bond
      distance of 2.069(3) angstroms. EXAFS spectra yield a mean Sc-O bond distance of
      2.09(1) angstroms for solvated scandium(III) ions in dimethyl sulfoxide solution,
      consistent with six-coordination. Raman and infrared absorption spectra have been
      recorded, also of the deuterated compound, and analysed by means of normal
      coordinate methods, together with spectra of dimethyl sulfoxide. The effects on
      the vibrational spectra of the weak intermolecular C-H...O interactions and of
      the dipole-dipole interactions in liquid dimethyl sulfoxide have been evaluated,
      in particular for the S-O stretching mode. The strong Raman band at 1043.6 cm(-1)
      and the intense IR absorption at 1062.6 cm(-1) have been assigned as the S-O
      stretching frequencies of the dominating species in liquid dimethyl sulfoxide,
      evaluated as centrosymmetric dimers with antiparallel polar S-O groups. The
      shifts of vibrational frequencies and force constants for coordinated dimethyl
      sulfoxide ligands in hexasolvated trivalent metal ion complexes are discussed.
      Hexasolvated scandium(iii) ions are found in dimethyl sulfoxide solution and in
      [Sc(OSMe(2))(6)]I(3). The iodide ion-dipole attraction shifts the methyl group C
      H stretching frequency for (S-)C-H...I(-) more than for the intermolecular (S-)C
      H...O interactions in liquid dimethyl sulfoxide.

PMID- 15558132
TI  - Chiral metal architectures in aminopyridinato complexes of zirconium.
AB  - Optically pure 2-alkylaminopyridines (HL) are synthesised readily from
      bromopyridines and chiral amines [(S)-1,2,3,4-tetrahydro-1-naphthylamine and (S)
      (-)-alpha-methylbenzylamine] using palladium-catalysed amination. Protonolysis
      reactions of these proligands with ZrX(4)(X = NMe(2), CH(2)Ph, CH(2)Bu(t)) yield
      zirconium aminopyridinates, usually of the type [ML(2)X(2)], some of which have
      been characterised by X-ray crystallography. Control of absolute configuration at
      the metal centre is pursued by investigation of the effects of chiral amine
      substituent, substitution at the pyridine rings and the identity of co-ligands.
      Surprisingly the conformationally flexible [small alpha]-methylbenzyl based
      aminopyridinato ligands promote much better control of chirality-at-zirconium
      than do the cyclic tetrahydronaphthyl analogues. One complex of the former class
      displays complete control of stereochemistry at 193 K; only one diastereomer out
      of eight possible structures is observed. It is found that there is an excellent
      correlation between observed selectivities and calculated diastereomer energy
      differences from DFT. All the complexes studied are in dynamic exchange between
      diastereomers. The rate of these processes (DeltaH ca. 40 kJ mol(-1)) as studied
      by Selective Polarisation Transfer-Selective Inversion Recovery experiments (SPT
      SIR) and lineshape analyses are significantly faster than those for
      aminopyridines containing bulkier amido substituents (DeltaH ca. 70 kJ mol(-1)).
      This type of dependence on steric effects, and the impact of the trans effect, is
      consistent with an N-dissociative mechanism, i.e. conversion from six- to five
      coordinate structure followed by rapid intramolecular scrambling.

PMID- 15558133
TI  - Formation and reactions of metal-metal bonded heterobimetallic (C5H4PR2)-bridged
      (Zr-Ir) and (Zr-Rh) complexes: evidence for the participation of metal hydride
      intermediates.
AB  - Treatment of the complexes [(C(5)H(4)PR(2))(2)Zr(CH(3))(2)](b: R = isopropyl; c:
      R = cyclohexyl) with the reagent HIr(CO)(PPh(3))(3) (2b) yield the
      heterobimetallic complexes [mu-C(5)H(4)PR(2))(2)(H(3)C-Zr-Ir(CO)(PPh(3)))] (4b,
      4c) with evolution of methane. The reaction of the -PPh(2) substituted analogue
      with initially yields an intermediate [(H(3)C)(2)Zr(mu
      C(5)H(4)PPh(2))(2)Ir(H)(CO)(PPh(3))] 5a, that still contains both methyl groups
      at zirconium and does not contain a metal-metal bond. At room temperature, the
      intermediate reacts further with methane formation to eventually yield the (Zr
      Ir) complex 4a. The corresponding [mu-C(5)H(4)PR(2))(2)(H(3)C-Zr-Rh(CO)(PPh(3)))]
      complexes 3a (R = Ph) and 3b (R = isopropyl) react cleanly with isopropyl alcohol
      to liberate methane and yield the corresponding [mu-C(5)H(4)PR(2))(2)(Me(2)CHO-Zr
      Rh(CO)(PPh(3)))] products (7a, 7b). Carefully monitoring the reaction of with
      Me(2)CHOH by NMR revealed that the Zr-Rh functionality is attacked first to give
      the intermediate [Me(Me(2)CHO)Zr([micro sign]-C(5)H(4)PR(2))(2)Rh(H)(CO)(PPh(3))]
      (6b). This intermediate then reacts further to cleave off methane and re-form the
      (Zr-Rh) metal-metal bond to yield the product 7b. The tetrametallic mu-oxo-(Zr
      Rh) metallocene derivate 11a was obtained starting from the (Zr-Rh) complex 3a
      and it was characterized by X-ray diffraction. It may be that this reaction is
      also initiated by H-OH addition to the [Zr-Rh] metal-metal bond.

PMID- 15558134
TI  - Reactivity of aqua coordinated monoporphyrinate lanthanide complexes: synthetic,
      structural and photoluminescent studies of lanthanide porphyrinate dimers.
AB  - Dimerization of monoporphyrinate lanthanide complexes [Yb(Por)(H(2)O)(3)]Cl, (Por
      = TTP(2-), TMPP(2-) and TPP(2-)) in the presence of sterically hindered tripodal
      ligand, zinc Schiff-base, dilute HCl, K(2)CO(3) solution, 4,4'-bipyridine (bipy),
      and basic 8-hydroxyquinaldine (HQ) solution was observed in CH(2)Cl(2) at room
      temperature. Six neutral dimeric lanthanide porphyrinate complexes, [Yb(TTP)(mu
      OH)](2)(mu-THF) (1), [Yb(TMPP)(mu-OH)(H(2)O)](2) (2), [Yb(TPP)(mu-OH)(mu
      H(2)O)](2) (4), [Yb(TMPP)(mu-Cl)(H(2)O)](2) (5), [Yb(TMPP)(mu-OH)](2)(THF) (6)
      and [Yb(TPP)](2)(mu-OH)(mu-Q) (7), were obtained. X-Ray diffraction studies
      showed that for the dimers, the two lanthanide ions were bridged by OH(-), Cl(-)
      or H(2)O. Photoluminescent studies showed that the porphyrinate dianion acted as
      an antenna, transferred its absorbed visible energy to the lanthanide ion and
      enabled the latter emitting in the near-infrared (NIR) region. In general, the
      NIR emission is more intense for the dimers than for the monomers, and the NIR
      emission intensity decreases as the number of O-H oscillators present in the
      molecule increases.

PMID- 15558135
TI  - Complexes of a dianionic bis(diphosphinomethanide) with lithium, sodium,
      potassium and zirconium. Effect of substitution on the Schlenk dimerisation of
      vinylidene phosphines.
AB  - The vinylidene phosphine (Pr(n)(2)P)(2)C=CH(2) (1) undergoes Schlenk dimerisation
      on treatment with an excess of any of the alkali metals Li, Na or K to give the
      butane-1,4-diide complexes [(L)M{(Pr(n)(2)P)(2)CCH(2)}](2)[(L)M =(THF)(2)Li (6),
      (THF)(3)Na (7b), (DME)(2)K (8b)], after recrystallisation. Whereas the reaction
      between the analogous phenyl derivative (Ph(2)P)(2)C=CH(2) and K results in
      cleavage of a P-C bond, 1 reacts smoothly with K to give 8, with no evidence for
      P-C cleavage. Compound 6 is an excellent ligand transfer reagent: metathesis
      reactions between either 6 or its phenyl analogue
      [(THF)(2)Li{(Ph(2)P)(2)CCH(2)}](2) (2) and two equivalents of Cp(2)ZrCl(2) in THF
      give the corresponding dinuclear zirconocene derivatives
      [Cp(2)Zr(Cl){(R(2)P)(2)CCH(2)}](2) in good yields [R = Ph (11), Pr(n)(12)].
      Compounds 6, 7b, 8b, 11 and 12 have been characterised by multi-element NMR
      spectroscopy and, where possible, by elemental analysis; compounds 6, 7b, 11 and
      12 have additionally been characterised by X-ray crystallography.

PMID- 15558138
TI  - Changing eating habits: what does it really mean for patients who do not complain
      about eating difficulties?

PMID- 15558139
TI  - The epidemiology of laryngeal cancer in Brazil.
AB  - The city of Sao Paulo exhibits one of the highest incidences of laryngeal cancer
      in world and Brazil presents remarkable occurrence, compared with other Latin
      American countries. Around 8,000 new cases and 3,000 deaths by laryngeal cancer
      occur annually in the Brazilian population. In the city of Sao Paulo, incidence
      rates for laryngeal cancer among males have been decreasing since the late 1980s
      while, among females, the rates have shown a stable trend. This phenomenon is
      probably the expression of changes in gender behavior related to tobacco smoking.
      Several risk factors are involved in the genesis of laryngeal cancer. The most
      important are tobacco smoking and alcohol intake, but occupational hazards have
      also been associated with the disease, such as asbestos, strong inorganic acids,
      cement dust and free crystalline silica. Additionally, salted meat and total fat
      intake have been linked to elevated risk of laryngeal cancer. Conversely, several
      studies have confirmed that fruits, raw leaf vegetables and legumes protect
      against this cancer. Some researchers have postulated a possible association
      between laryngeal squamous cell carcinoma and human papilloma virus (HPV), but
      this is not universally accepted. Gastroesophageal reflux disease is weakly, but
      consistently correlated with laryngeal cancer. Familial cancer clusters,
      particularly of head and neck tumors, seem to increase the risk of laryngeal
      cancer. Some genetic polymorphisms, such as of genes that code for xenobiotic
      metabolizing enzymes, have shown elevated risk for laryngeal cancer according to
      recent studies. Public health policies regarding the control of tobacco smoking
      and alcohol consumption, and also surveillance of carcinogen exposure in
      occupational settings, could have an impact on laryngeal cancer. No proposals for
      screening have been recommended for laryngeal cancer, but one diagnostic goal
      should be to avoid treatment delay when suspected symptoms have been observed.

PMID- 15558140
TI  - Changes in eating habits following total and frontolateral laryngectomy.
AB  - CONTEXT: Swallowing is a continuous dynamic process, characterized by complex
      stages, that involves structures of the oral cavity, pharynx, larynx and
      esophagus. It can be divided into three phases: oral, pharyngeal and esophageal.
      Dysphagia is characterized by difficulty with, or the inability to swallow food
      of normal consistencies. OBJECTIVE: To investigate the presence of swallowing
      difficulties and modifications made to the consistency of the food consumed in
      cases of total and partial laryngectomy, with or without subsequent radiotherapy,
      among patients who had not been diagnosed as having dysphagia. TYPE OF STUDY:
      Descriptive study. SETTING: Voice Clinic of Sao Paulo Hospital, Universidade
      Federal de Sao Paulo/Escola Paulista de Medicina, Sao Paulo, Brazil. METHOD: 36
      laryngectomy patients: 25 total and 11 frontolateral cases, were studied. A
      survey consisting of a 23-item questionnaire was applied by a single
      professional. RESULTS: Among those interviewed, 44% reported having modified the
      consistency of the food consumed (56% of the total and 20% of the partial
      frontolateral laryngectomy cases). It was not possible to investigate the
      influence of radiotherapy on the groups in this study, because the partial
      frontolateral laryngectomy cases were not exposed to radiotherapy. There was a
      higher incidence of complaints of swallowing difficulties in total laryngectomy
      cases (p < 0.027) than in partial frontolateral cases. However, there was no
      relationship between the surgery and weight loss. We also noted the patients'
      other problems regarding the eating process, as well as the compensation that
      they made for such problems. DISCUSSION: Research has shown an association
      between laryngectomy and swallowing difficulties, although there have been no
      reports of associated changes in eating habits among laryngectomized patients.
      CONCLUSIONS: This study showed that difficulty in swallowing is not rare in total
      and frontolateral laryngectomy cases. Such patients, even those who did not
      complain of dysphagia, also had minor difficulties while eating, and had to make
      some adaptations to their meals.

PMID- 15558141
TI  - Laryngeal sensitivity evaluation and dysphagia: Hospital Sirio-Libanes
      experience.
AB  - CONTEXT: Laryngeal sensitivity is important in the coordination of swallowing
      coordination and avoidance of aspiration. OBJECTIVE: To briefly review the
      physiology of swallowing and report on our experience with laryngeal sensitivity
      evaluation among patients presenting dysphagia. TYPE OF STUDY: Prospective.
      SETTING: Endoscopy Department, Hospital Sirio-Libanes. METHODS: Clinical data,
      endoscopic findings from the larynx and the laryngeal sensitivity, as assessed
      via the Flexible Endoscopic Evaluation of Swallowing with Sensory Testing
      (FEESST) protocol (using the Pentax AP4000 system), were prospectively studied.
      The chi-squared and Student t tests were used to compare differences, which were
      considered significant if p < or = 0.05. RESULTS: The study included 111
      patients. A direct association was observed for hyperplasia and hyperemia of the
      posterior commissure region in relation to globus (p = 0.01) and regurgitation (p
      = 0.04). Hyperemia of the posterior commissure region had a direct association
      with sialorrhea (p = 0.03) and an inverse association with xerostomia (p = 0.03).
      There was a direct association between severe laryngeal sensitivity deficit and
      previous radiotherapy of the head and neck (p = 0.001). DISCUSSION: These data
      emphasize the association between proximal gastroesophageal reflux and chronic
      posterior laryngitis, and suggest that decreased laryngeal sensitivity could be a
      side effect of radiotherapy. CONCLUSIONS: Even considering that these results are
      preliminary, the endoscopic findings from laryngoscopy seem to be important in
      the diagnosis of proximal gastroesophageal reflux. Study of laryngeal sensitivity
      may have the potential for improving the knowledge and clinical management of
      dysphagia.

PMID- 15558142
TI  - Inflammatory mediators in nasal lavage among school-age children from urban and
      rural areas in Sao Paulo, Brazil.
AB  - CONTEXT: Some studies have shown that inflammatory processes in the nasal air
      passages may reflect or affect those in the lower airways. We decided to
      indirectly assess the inflammatory status of the nasal airways in two groups of
      children with different sensitization rates to aeroallergens. OBJECTIVE: To
      compare the inflammatory activity in the nasal airways, through the determination
      of mediators in nasal lavage fluid in two distinct populations. TYPE OF STUDY:
      Cross-sectional study. SETTING: Two public elementary schools, one in an urban
      setting and the other in a rural setting of the State of Sao Paulo, Brazil.
      METHODS: Two groups of 40 elementary school children with different sensitization
      rates to aeroallergens were formed. Samples of nasal lavage fluid were assessed
      for eosinophil cationic protein (ECP) and tryptase. Non-parametric tests were
      used for statistical analysis. RESULTS: Significantly higher levels of ECP were
      observed among students living in the urban area than those in the rural area (p
      < 0.05). No significant difference in the tryptase levels was observed. Also, the
      urban children who were sensitized to aeroallergens presented higher levels of
      ECP in nasal mucosa than the non-sensitized children, while this difference was
      not observed among the rural children. DISCUSSION: The lack of mast cell activity
      and increased eosinophil degranulation revealed a chronic inflammatory state in
      the nasal air passages. The higher eosinophil activity in the urban area,
      coinciding with higher sensitization to aeroallergens, suggests that there must
      be some factors in the urban area that can modulate airway inflammation by
      influencing the activation of inflammatory cells. CONCLUSION: Our findings showed
      that there was no difference in the concentrations of tryptase in nasal lavage
      fluids between the two studied groups. However, the children from the urban area
      presented with higher concentrations of eosinophil cationic protein than did
      those from the rural area. Also, the urban children who were sensitized to
      aeroallergens presented with greater concentrations of eosinophil cationic
      protein in nasal mucosa than the non-sensitized children, while this difference
      was not observed among the rural children.

PMID- 15558143
TI  - Treatment of bone pain secondary to metastases using samarium-153-EDTMP.
AB  - CONTEXT: More than 50% of patients with prostate, breast or lung cancer will
      develop painful bone metastases. The purpose of treating bone metastases is to
      relieve pain, reduce the use of steroids and to maintain motion. OBJECTIVE: To
      evaluate the use of samarium-153-EDTMP (153Sm-EDTMP) for the treatment of bone
      pain secondary to metastases that is refractory to clinical management. TYPE OF
      STUDY: Retrospective. SETTING: Division of Nuclear Medicine, Universidade
      Estadual de Campinas (Unicamp). METHODS: Fifty-eight patients were studied (34
      males) with mean age 62 years; 31 patients had prostate cancer, 20 had breast
      cancer, three had lung cancer, one had lung hemangioendothelioma, one had
      parathyroid adenocarcinoma, one had osteosarcoma and one had an unknown primary
      tumor. All patients had multiple bone metastases demonstrated by bone
      scintigraphy using 99mTc-MDP,and were treated with 153Sm-EDTMP. Response to
      treatment was graded as good (pain reduction of 50-100%), intermediate (25-49%)
      and poor (0-24%). RESULTS: All patients showed good uptake of 153Sm-EDTMP by bone
      metastases. Among the patients with prostate cancer, intermediate or good
      response to therapy occurred in 80.6% (25 patients) and poor response in 19.4%
      (6). Among the patients with breast cancer, 85% (17) showed intermediate or good
      response to therapy while 15% (3) showed poor response. All three patients with
      lung cancer showed poor response to treatment. The lung hemangioendothelioma and
      unknown primary lesion patients showed intermediate response to treatment; the
      osteosarcoma and parathyroid adenocarcinoma patients showed good response to
      treatment. No significant myelotoxicity occurred. DISCUSSION: Pain control is
      important for improving the quality of life of patients with advanced cancers.
      The mechanism by which pain is relieved with the use of radionuclides is still
      not yet completely understood, however, the treatment is simple and provides a
      low risk of mielotoxicity. CONCLUSION: Treatment with 153Sm-EDTMP can control the
      pain secondary to bone metastases effectively in most patients with breast and
      prostate cancer without significant side effects.

PMID- 15558144
TI  - Primary epidural malignant hemangiopericytoma of thoracic spinal column causing
      cord compression: case report.
AB  - CONTEXT: Hemangiopericytoma is an uncommon mesenchymal neoplasm that rarely
      affects the spinal canal. Primary malignant hemangiopericytoma of the spinal
      column is extremely rare. CASE REPORT: We report on a case of primary epidural
      malignant hemangiopericytoma of the thoracic spinal column that invaded vertebral
      bone and caused spinal cord compression in a 21-year-old man. The patient
      presented with progressive back pain over a four-month period that progressed to
      paraparesis, bilateral leg paresthesia and urinary incontinence. The surgical
      intervention involved laminectomy and subtotal resection of the tumor, with
      posterior vertebral fixation. Postoperative involved-field radiotherapy was
      administered. A marked neurological improvement was subsequently observed. We
      describe the clinical, radiological, and histological features of this tumor and
      review the literature.

PMID- 15558145
TI  - Head and neck hemangiopericytoma in a child: case report.
AB  - CONTEXT: Hemangiopericytoma is a relatively rare tumor, first described in 1942,
      with approximately 300 cases described in the literature to date. In most cases,
      it affects the trunk and lower extremities. The head and neck incidence is less
      than 20%, mostly in adults. We describe a case of malignant head and neck
      hemangiopericytoma in a child. TYPE OF STUDY: Case report. CASE REPORT: A twelve
      year-old male patient noted the presence of a firm painless right-side
      retroauricular lymph node of 1 cm in diameter, which at first remained unchanged
      for six months, but subsequently enlarged progressively. He denied having had
      previous trauma at that site. In November 2000, he presented nasal obstruction
      and voluminous epistaxis that required hospitalization and blood transfusion.
      During dental treatment one month later, a cranial x-ray revealed bone
      alterations. A subsequent computed tomography scan showed an extensive lesion of
      soft tissue density that had invaded the maxillary fossa, eroding the skull base
      and middle and nasal fossa. The child was then referred to our service, where
      biopsy was performed, giving a diagnosis of hemangiopericytoma. Shortly
      afterwards, magnetic resonance imaging revealed that this lesion had undergone
      significant growth, while maintaining the same invasion pattern. The patient was
      submitted to conservative surgery in April 2001, with only partial resection of
      the tumor because of its extent. Histopathological examination of the specimen
      confirmed the presence of malignant hemangiopericytoma. Following the surgery,
      the patient presented fast regrowth of the lesion, with partial response to
      chemotherapy and radiotherapy.

PMID- 15558146
TI  - Cones in the Euclidean space with vanishing scalar curvature.
AB  - Given a hypersurface M on a unit sphere of the Euclidean space, we define the
      cone based on M as the set of half-lines issuing from the origin and passing
      through M. By assuming that the scalar curvature of the cone vanishes, we obtain
      conditions under which bounded domains of such cone are stable or unstable.

PMID- 15558147
TI  - A relation between the right triangle and circular tori with constant mean
      curvature in the unit 3-sphere.
AB  - In this note we will show that the inverse image under the stereographic
      projection of a circular torus of revolution in the 3-dimensional euclidean space
      has constant mean curvature in the unit 3-sphere if and only if their radii are
      the catet and the hypotenuse of an appropriate right triangle.

PMID- 15558148
TI  - Numbers for reducible cubic scrolls.
AB  - We show how to compute the number of reducible cubic scrolls of codimension 2 in
      Pn incident to the appropriate number of linear spaces.

PMID- 15558149
TI  - Flavonoids from Lonchocarpus muehlbergianus.
AB  - The light petroleum extract from the roots of Lonchocarpus muehlbergianus Hassl
      contained nine flavonoids, including six new ones. These are 2,4-cis-2,4,5,8
      tetramethoxy-(2'',3'':6,7)-furanoflavan; 2,4-cis-4-hydroxy-2,5,8-trimethoxy
      (2'',3'':6,7)-furanoflavan; 2,4-cis-2-prenyloxy-4,5,8-trimethoxy-(2'',3'':6,7)
      furanoflavan; 2,4-cis-2-prenyloxy-4-hydroxy-5,8-dimethoxy-(2'',3'':6,7)
      furanoflavan; 2',5',6'-trimethoxy-9-(1,1-dimethylallyoxy)-[2'',3'':3',4']
      furanochalcone; 5,6-dimethoxy-(2'',3'':7,8)-furanoflavone, identified by analysis
      of their spectral data (UV, IR, 1H and 13C NMR, 2D-NMR, NOE and MS). The natural
      occurrence of 2,4-dioxygenated flavan derivatives is being reported for the first
      time. Quantitative analysis of the petrol extract, by using reversed-phase HPLC,
      showed that the most abundant flavonoid in the extract is 2,4-cis-2,4,5,8-
      tetramethoxy-(2'',3'':6,7)-furanoflavan.

PMID- 15558150
TI  - On the geographical differentiation of Gymnodactylus geckoides Spix, 1825
      (Sauria, Gekkonidae): speciation in the Brazilian caatingas.
AB  - The specific concept of G. geckoides was initially ascertained based on a
      topotypical sample from Salvador, Bahia. Geographic differentiation was studied
      through the analysis of two meristic characters (tubercles in a paramedian row
      and fourth toe lamellae) and color pattern of 327 specimens from 23 localities.
      It is shown that the population from the southernmost locality, Mucuge, is
      markedly divergent in all characters studied. A Holocene refuge model is proposed
      to explain the pattern. A decision about the rank to be attributed to the Mucuge
      population is deferred until more detailed sampling is effected and molecular
      methods are applied.

PMID- 15558151
TI  - Inactivation of yeast inorganic pyrophosphatase by organic solvents.
AB  - A number of application for enzymes in organic solvents have been developed in
      chemical processing, food related conversions and analyses. The only unsolved
      problem related to nonaqueous enzymology is the notion that enzymes in organic
      solvent are mostly far less active than in water. Therefore, studies concerning
      the mechanisms by which enzymes are inactivated by organic solvents would reveal
      a clear understanding of the structure-function relationship of this phenomenon.
      Here we analyzed the effects of a series of alcohols (methanol, ethanol, 1
      propanol and 2-propanol) and acetone on the activity of yeast inorganic
      pyrophosphatase. We observed that solvents inactivated the enzyme in a dose
      dependent manner. This inactivation is also dependent on the hydrophobicity of
      the solvent, where the most hydrophobic solvent is also the most effective one.
      The I50 for inactivation by n-alcohols are 5.9 +/- 4, 2.7 +/- 1 and 2.5 +/- 1 M
      for methanol, ethanol and 1-propanol, respectively. Inactivation was less
      effective at 37 degrees C than at 5 degrees C, when the I50 for inactivation by
      methanol, ethanol and 1-propanol are 4.5 +/- 2, 2.1 +/- 2 and 1.7 +/- 1 M,
      respectively. Our proposal is that solvent binds to the enzyme structure
      promoting the inactivation by stabilizing an unfolded structure, and that this
      binding is through the hydrophobic regions of either the protein or the solvent.

PMID- 15558152
TI  - Clinical and laboratory aspects of common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is an immunological disorder
      characterized by defective antibody production, recurrent infections, most
      notably of the respiratory tract, autoimmune phenomena and cancer. Some CVID
      patients may also present disturbances of the cellular immune response such as a
      decrease in the number and proportion of different lymphocyte populations,
      diminished lymphoproliferative response to mitogens and antigens, altered
      production of cytokines, and deficient expression of cell-surface molecules. Most
      Brazilian CVID patients included in this study show a decrease in T and B
      lymphocyte counts in the peripheral blood. Furthermore, their lymphocytes are
      more susceptible to apoptosis following activation than normal individuals, and
      they have a decrease in the expression of activation molecules like CD25, CD69,
      CD40L and CD70. Moreover, they show a decreased synthesis of IL-4 and IL-5 in
      comparison with normal individuals. The increase in susceptibility to apoptosis
      following activation, may also be responsible for the decrease in the expression
      of activation molecules and CD40L, decrease in Th2 cytokines synthesis, and in
      the number of T and B circulating cells. In this study we discuss some of these
      immunological disturbances correlating them to the patients' clinical features
      and comparing our patients' findings to the literature.

PMID- 15558153
TI  - Overview of genotypic and clinical profiles of human immunodeficiency virus type
      1-infected children in Rio de Janeiro, Brazil.
AB  - Although mother-to-child HIV transmission prevention has slowed down pediatric
      HIV infection in developed countries, large numbers of infants still become
      infected in developing nations. Data on pediatric HIV infection is however
      largely scarce. In this study, we have overviewed clinical, laboratory and
      genotypic data from a large cohort of HIV-infected infants regularly followed at
      two pediatric HIV outpatient clinics in Rio de Janeiro, Brazil. Children on
      antiretroviral therapy, as well as drug-naive, newly diagnosed infants were
      analyzed. Prevalence of drug resistance mutations, as well as immunological and
      virological responses to therapy were evaluated. Additionally, HIV-1 subtype
      frequencies and their distribution over the course of the epidemic were studied.
      We have found a high prevalence of mutations among ARV-experienced children,
      whereas mutations were absent in the drug-naive group. Despite the high levels of
      resistance among treated infants, an important improvement of their immunological
      status was observed. HIV-1 subtype distribution followed the trends of the adult
      population, with the appearance of non-B subtypes and recombinant forms after
      1990. To our knowledge, this is the largest pediatric cohort ever analyzed in
      Brazil, and the data provided is of paramount importance to a better
      understanding of HIV/AIDS evolution in pediatric settings.

PMID- 15558154
TI  - Gap junctions in hematopoietic stroma control proliferation and differentiation
      of blood cell precursors.
AB  - We examined gap junction communication in an in vitro model of hematopoiesis,
      using the murine bone marrow stroma cell line S-17, and primary cultures of
      murine marrow-derived blood cell precursors. S-17 cells express several
      connexins, the major one being connexin 43. Connexin expression and formation of
      functional gap junctions is modulated by stroma cell density. Transfection of S
      17 cells with a vector containing connexin 43 sense or anti-sense sequences
      increased or decreased, respectively, connexin 43 synthesis and intercellular dye
      coupling. Under these conditions, modulation of gap junction-mediated
      communication modified the growth pattern of stroma itself, as well as the
      ability of the stroma to sustain hematopoiesis. Increased connexin 43 expression
      was associated with a delay in differentiation of blood cells, resulting in
      increased production of hematopoietic precursors, while decreased connexin 43
      expression elicited an accelerated differentiation of myeloid blood cell
      precursor cells. These results suggest that connexin-mediated coupling in the
      stroma modulates the ratio between proliferation and differentiation of
      hematopoietic precursors. We therefore propose that increased gap junction
      communication in the stroma elicits an enhanced production of immature bone
      marrow cells through the delay in their terminal differentiation, inducing
      consequently an extended proliferation period of blood cell precursors.

PMID- 15558155
TI  - Solvent-related chronic toxic encephalopathy as a target in the worker's mental
      health research.
AB  - The article is aimed at discussing the theoretical grounds which support the
      diagnosis of solvent-related chronic encephalopathy in the field of the worker's
      mental health, having it as a target in this area. The psychiatric, neurological
      and labor health postulates which contribute to the multidisciplinary description
      of such diagnostic category are presented.

PMID- 15558160
TI  - Human toxocariasis: a seroepidemiological survey in schoolchildren of Sorocaba,
      Brazil.
AB  - A seroepidemiological survey for toxocariasis, among 180 schoolchildren of the
      public schools of Sorocaba City, state of Sao Paulo, Brazil, was carried out from
      August 2000 to July 2001. ELISA test was performed using excretory and secretory
      antigens for the detection of IgG anti-Toxocara antibodies. Information regarding
      the children was obtained from the parents or legal guardians. The results showed
      that the mean age was 5.4 +/- 1.4 years, the infection coefficient (IC) was 38.3
      and the infection risk was higher among the children living in the city outskirts
      (IC = 47.4) where the socioeconomic conditions were worse than in the central
      region of the city (IC = 11.1). There was an association between higher frequency
      of seroreactivity in the ELISA test and the condition of living in a house with a
      yard and/or unpaved street. The same was observed in relation to a history of
      enteroparasitism. There was also an association between a seronegative ELISA test
      and previous treatment of pet dogs and/or cats with vermifuge. Based on these
      results, the authors propose that public health programs should include
      anthelmintic for dogs and cats during the antirabies vaccination campaigns, in
      order to diminish environmental contamination with Toxocara spp. eggs and
      consequently human infection.

PMID- 15558161
TI  - Diarrheagenic Escherichia coli categories among the traditional enteropathogenic
      E. coli O serogroups--a review.
AB  - The so called enteropathogenic Escherichia coli (EPEC) O serogroups include
      typical and atypical EPEC, enterohaemorrragic E. coli, enterotoxigenic E. coli,
      and enteroaggregative E. coli. The aim of this article is to review the
      composition of each O serogroup and the major serotypes, clones, and additional
      virulence characteristics of each of these diarrheagenic categories. Their
      adherence patterns and genetic relationships are also presented. The review is
      based on the study of 805 strains of serogroups O26, O55, O86, O111, O114, O119,
      O125, O126, O1127, O128, and O142 most of which isolated in Sao Paulo from
      children with diarrhea between 1970 and 1990. Since some O serogroups include
      more than one diarrheagenic category O serogrouping only should be abandoned as a
      diagnostic method. However serotyping is a reliable method for those serotypes
      that correspond to clones.

PMID- 15558162
TI  - Association of human leukocyte antigen DQ1 and dengue fever in a white Southern
      Brazilian population.
AB  - Dengue is an infectious disease of viral etiology transmitted by the mosquitoes
      Aedes aegypti, A. albopictus, and A. scutellaris. It can develop either as a
      benign form or as a severe hemorrhagic form. Previous work showed an association
      of the hemorrhagic form with human leukocyte antigens (HLA), suggesting a role of
      genetic factors in disease susceptibility. Nevertheless, data on HLA association
      with the classical form of the disease is scarce in literature. Sixty-four
      patients and 667 normal individuals, living in the state of Parana, Southern
      Brazil, were used as test and control group, respectively. The patients developed
      the disease during a virus 1 dengue outbreak either in Maringa city in 1995 (47)
      or in Paranavai city in 1999 (17). The diagnostic was confirmed through serology
      and/or viral culture. HLA class I and II typing was performed by the classical
      microlynfocitotoxicity test using monoclonal antisera and fluorobeads. Qui-square
      statistical analysis confirmed a positive association with HLA-DQ1 (76.6% vs
      57.7%; p = 0.005243; pc = 0.026215). HLA-DR1 also presented an increased
      frequency in the test group, not statistically significant after p correction
      though (32.8% vs 15.9%; p = 0.005729; pc = 0.080206). In conclusion, genetic
      factors may play a role on the susceptibility to the classical dengue, virus 1,
      in the Brazilian population. Further independent studies should be performed in
      the Brazilian population to confirm these preliminary data.

PMID- 15558163
TI  - Intestinal helminths of capybaras, Hydrochoerus hydrochaeris, from Venezuela.
AB  - Quantitative parameters of intestinal helminth species and their potential
      relations to host characteristics in a population of capybaras (Hydrochoerus
      hydrochaeris) from Venezuela are reported for the first time. The intestines of
      40 capybaras were collected during the 1992-annual harvest at Hato El Cedral. Six
      helminth species were found: 2 cestodes (Monoecocestus macrobursatum, M.
      hagmanni), 2 nematodes (Viannella hydrochoeri, Protozoophaga obesa), and 2
      trematodes (Hippocrepis hippocrepis, Taxorchis schistocotyle). This is the first
      report for M. macrobursatum in Venezuela. Helminth abundance did not differ
      between sexes or age classes. Although patterns of distribution for all helminth
      species were overdispersed, the high prevalence found for all species (over 70%)
      and the high abundance observed for nematodes made it difficult to assess the
      effect that these helminths may produce on capybaras. Nevertheless, the negative
      associations found between the body condition of capybaras and helminth intensity
      for M. macrobursatum and V. hydrochoeri, might be pointing out potential host
      population regulatory role for these parasites which require further research.

PMID- 15558164
TI  - Lymnaea cousini Jousseaume, 1887 (Gastropoda: Lymnaeidae): first record for
      Venezuela.
AB  - Lymnaea cousini Jousseaume, 1887 was collected in Mucubaji, Merida State,
      Venezuela, from a permanent pond located at a very high altitude (3760 m).
      Identification of the collected specimens was made by comparison with the
      original description of the shell by Jousseaume and the description of the renal
      organ and reproductive system of topotypic specimens by Paraense.

PMID- 15558165
TI  - Feeding preference of the sand flies Lutzomyia umbratilis and L. spathotrichia
      (diptera: Psychodidae, Phlebotominae) in an urban forest patch in the city of
      Manaus, Amazonas, Brazil.
AB  - Precipitin tests were performed on blood meals of 199 sand flies (161 Lutzomyia
      umbratilis, 34 L. spathotrichia, two Lutzomyia of group shannoni, one L. anduzei)
      in a non-flooded upland forest on the Campus of the Universidade Federal do
      Amazonas. This is the second largest forest fragment in an urban setting in
      Brazil. Results on L. umbratilis, which is considered to be the principal
      leishmaniasis vector in this region, indicated rodents as its predominant blood
      source in contrast to previous reports in which blood meal analysis indicated
      that this species fed principally on Xenarthra (particularly sloths).

PMID- 15558166
TI  - Study of hantavirus infection in captive breed colonies of wild rodents.
AB  - Wild sigmondontine rodents are known to be the reservoir of several serotypes of
      New World hantaviruses. The mechanism of viral transmission is by aerosol
      inhalation of the excreta from infected rodents. Considering that the captive
      breed colonies of various wild mammals may present a potential risk for
      hantaviral transmission, we examined 85 specimens of Thrichomys spp. (Echimyidae)
      and 17 speciemens of Nectomys squamipes (Sigmodontinae) from our colony for the
      presence of hantavirus infections. Blood samples were assayed for the presence of
      antibodies to Andes nucleocapsid antigen using enzyme-linked immunosorbent assay
      (ELISA). Additionally, serum samples from workers previously exposed to wild
      rodents, in the laboratories where the study was conducted, were also tested by
      ELISA to investigate prevalence of anti-hantavirus IgG antibodies. All blood
      samples were negative for hantavirus antibodies. Although these results suggest
      that those rodent's colonies are hantavirus free, the work emphasizes the need
      for hantavirus serological monitoring in wild colonized rodents and secure
      handling potentially infected rodents as important biosafety measures.

PMID- 15558167
TI  - Blood and intestinal parasites of squirrels (Rodentia: Sciuridae) in Amazonian
      Brazil.
AB  - We report the result of an examination for blood and intestinal protozoa in 12
      specimens of the red squirrel Sciurus spadiceus (Rodentia: Sciuridae) from
      Birroque, municipality of Placido de Castro, state of Acre, Brazil. No parasites
      were detected in thin, Giemsa-stained blood films of the animals, but culture of
      the blood of three in Difco B45 medium blood-agar slants gave rise to isolates of
      epimastigotes. Inoculation of one isolate into laboratory mice resulted in the
      appearance of Trypanosoma cruzi-like trypomastigotes in their peripheral blood,
      and the other two isolates gave rise to transient infections with a T. lewisi
      like parasite in inoculated mice and hamsters. The failure of the latter parasite
      to develop in the triatomine bug Rhodnius robustus suggests that it is probably
      not T. rangeli. This appears to be the first record of a T. lewisi-like
      trypanosome in neotropical squirrels. Oocysts of an Eimeria sp., were detected in
      the faeces of 10 animals (83.3%). The parasite develops in the epithelial cells
      of the intestine, where it may cause severe damage and sometimes results in death
      of the animal. No oocysts were detected in bile.

PMID- 15558168
TI  - Biologic data of Macaca mulatta, Macaca fascicularis, and Saimiri sciureus used
      for research at the Fiocruz primate center.
AB  - Physiological parameters of laboratory animals used for biomedical research is
      crucial for following several experimental procedures. With the intent to
      establish baseline biologic parameters for non-human primates held in closed
      colonies, hematological and morphometric data of captive monkeys were determined.
      Data of clinically healthy rhesus macaques (Macaca mulatta), cynomolgus monkeys
      (Macaca fascicularis), and squirrel monkeys (Saimiri sciureus) were collected
      over a period of five years. Animals were separated according to sex and divided
      into five age groups. Hematological data were compared with those in the
      literature by Student's t test. Discrepancies with significance levels of 0.1, 1
      or 5% were found in the hematological studies. Growth curves showed that the
      sexual dimorphism of rhesus monkeys appeared at an age of four years. In earlier
      ages, the differences between sexes could not be distinguished (p < 0.05). Sexual
      dimorphism in both squirrel monkeys and cynomolgus monkeys occurred at an age of
      about 32 months. Data presented in this paper could be useful for comparative
      studies using primates under similar conditions.

PMID- 15558169
TI  - [Life cycle of Rhodnius brethesi Matta, 1919 (Hemiptera, Reduviidae,
      Triatominae), a potential vector of Chagas disease in the Amazon region].
AB  - R. brethesi is a sylvatic species from the Amazon region; it has been
      incriminated as responsible for the transmission of Chagas disease in collectors
      of piacaba in this region. The aim of present study was to investigate the
      efficiency of these insects as potential vectors of Trypanosoma cruzi. Aspects
      related with feeding and defecation patterns, life time, and mortality had been
      observed in each instar of R. brethesi. We use 5th instar nymphs to get adults
      virgins, after the moulting 3 groups with 6 females and 2 males each were created
      to obtain eggs. After hatching, 1st instar nymphs had been weighed and kept in
      bottles until the next moult. Insects were fed once a week in mice. Results
      showed that the average period of incubation was 17 days, the number of blood
      meal was increasing from the 1st to the 5th instar nymph with 7 (average) to
      become adult, a significative numbers of the defecations occurring immediately
      after the bloodmeals. The total percentual of mortality was 16%. This results
      suggests that this species presents a good exploitation of blood meals and a
      brief nymphal development in laboratory conditions reflecting its behavior in
      sylvatic environments.

PMID- 15558170
TI  - Biology of the first generation of a laboratory colony of Nyssomyia intermedia
      (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae).
AB  - The phlebotomine sand flies Nyssomyia intermedia (Lutz & Neiva, 1912) and
      Nyssomyia neivai (Pinto, 1926) are very close and may be involved in the
      transmission of Leishmania spp. Ross, 1903 in Brazil. The biology of the first
      laboratory-reared generations of these species, descended from insects captured
      in Alem Paraiba (N. intermedia) and Corinto (N. neivai) in the Brazilian state of
      Minas Gerais, is described here. The captured females were fed on hamsters and
      maintained individually in rearing pots. Laboratory temperature and relative
      humidity were maintained at 25-26 masculineC and 80% respectively. The
      productivity of the first generation of N. intermedia was greater than that of N.
      neivai, and its development time clearly shorter, particularly for the second and
      third larval instars.

PMID- 15558171
TI  - Life tables and reproductive parameters of Lutzomyia spinicrassa (Diptera:
      Psychodidae) under laboratory conditions.
AB  - Lutzomyia spinicrassa is a vector of Leishmania braziliensis in Colombia. This
      sand fly has a broad geographical distribution in Colombia and Venezuela and it
      is found mainly in coffee plantations. Baseline biological growth data of L.
      spinicrassa were obtained under experimental laboratory conditions. The
      development time from egg to adult ranged from 59 to 121 days, with 12.74 weeks
      in average. Based on cohorts of 100 females, horizontal life table was
      constructed. The following predictive parameters were obtained: net rate of
      reproduction (8.4 females per cohort female), generation time (12.74 weeks),
      intrinsic rate of population increase (0.17), and finite rate of population
      increment (1.18). The reproductive value for each class age of the cohort females
      was calculated. Vertical life tables were elaborated and mortality was described
      for the generation obtained of the field cohort. In addition, for two successive
      generations, additive variance and heritability for fecundity were estimated.

PMID- 15558172
TI  - Description of Micropygomyia (Silvamyia) echinatopharynx sp. nov. (Diptera:
      Psychodidae) a new species of phlebotomine sand fly from the state of Tocantins,
      Brazil.
AB  - During a study of the phlebotomines of the Brazilian state of Tocantins, a new
      species was discovered in Porto Nacional county, here described as Micropygomyia
      (Silvamyia) echinatopharynx sp. nov. This is only the second species of the
      subgenus Micropygomyia (Silvamyia) to be described.

PMID- 15558173
TI  - Trypanosoma cruzi: establishment of permeable cells for RNA processing analysis
      with drugs.
AB  - Pre-mRNA maturation in trypanosomatids occurs through a process called trans
      splicing which involves excision of introns and union of exons in two independent
      transcripts. For the first time, we present the standardization of Trypanosoma
      cruzi permeable cells (Y strain) as a model for trans-splicing study of mRNAs in
      trypanosomes, following by RNase protection reaction, which localizes the SL exon
      and intron. This trans-splicing reaction in vitro was also used to analyze the
      influence of NFOH-121, a nitrofurazone-derivative, on this mechanism. The results
      suggested that the prodrug affects the RNA processing in these parasites, but the
      trans-splicing reaction still occurred.

PMID- 15558174
TI  - Experimental kinetics of infection induced by Yersinia pseudotuberculosis
      isolated from stock animals.
AB  - The course of in vivo infection of five isolates of Yersinia pseudotuberculosis
      was followed for three weeks in Swiss mice. The strains were isolated from
      diarrheic and normal feces and mesenteric lymph nodes of healthy and sick stock
      animals. Four strains of serogroup O:3 and one of serogroup O:1a, with and
      without the virulence plasmid, were inoculated intragastrically and intravenously
      in the mice. Groups of five animals were sacrificed at 6 h and 3, 6, 10, 15, and
      21 days after inoculation, and organs and tissues were checked for possible
      macroscopic alterations. Development of infection was monitored at these times by
      performing viable bacterial counts in homogenates of selected tissues. The
      animals were checked daily for clinical alterations. The results of the study
      showed that strains with the virulence plasmid infected organs and tissues at
      various times and at varying intensity by both routes of infection, the strain of
      type O:1a being the most invasive. Moreover, clinical and pathological
      alterations occurred only in animals inoculated with bacteria carrying the
      virulence plasmid, regardless of the route of infection.

PMID- 15558175
TI  - Larval recovery of Toxocara canis in organs and tissues of experimentally
      infected Rattus norvegicus.
AB  - The aim of this note was to record for the first time the recovery of Toxocara
      canis larvae from tissues and organs of Rattus norvegicus (Berkenhout, 1769),
      Wistar strain, until the 60th day after experimental infection. Rats were orally
      infected with embryonated T. canis eggs, killed on days 3, 5, 8, 10, 15, 30, and
      60 after inoculation and larvae were recovered from liver, lungs, kidneys, brain,
      and carcass after acid digestion, showing a pattern of migration similar of that
      previously observed in mice.

PMID- 15558176
TI  - In situ hybridization of hepatitis C virus RNA in liver cells of an
      experimentally infected rhesus macaque.
AB  - The liver tissue of a rhesus macaque inoculated with hepatitis C virus (HCV) has
      been analyzed for the presence of HCV RNA using the technique of in situ
      hybridization, both at light and electron microscopy levels. The animal was
      inoculated by the intrasplenic route using a HCV infected autogenic hepatocyte
      transplant. The serum sample used to infect the hepatocyte cells was
      characterized by polymerase chain reaction technique and shown to be positive for
      HCV RNA, genotype 3 with 10(7) RNA copies/ml. In situ hybridization was performed
      using a complementary negative strand probe made with the specific primer. We
      were able to detect and localize viral RNA in altered membranes of the rough
      endoplasmic reticulum of infected liver cells, showing evidence of virus
      replication in vivo.

PMID- 15558177
TI  - Detection of Brazilian hantavirus by reverse transcription polymerase chain
      reaction amplification of N gene in patients with hantavirus cardiopulmonary
      syndrome.
AB  - We report a nested reverse transcription-polymerase chain reaction (RT-PCR) assay
      for hantavirus using primers selected to match high homology regions of
      hantavirus genomes detected from the whole blood of hantavirus cardiopulmonary
      syndrome (HCPS) patients from Brazil, also including the N gene nucleotide
      sequence of Araraquara virus. Hantavirus genomes were detected in eight out of
      nine blood samples from the HCPS patients by RT-PCR (88.9% positivity) and in all
      9 blood samples (100% positivity) by nested-PCR. The eight amplicons obtained by
      RT-PCR (P1, P3-P9), including one obtained by nested-PCR (P-2) and not obtained
      by RT-PCR, were sequenced and showed high homology (94.8% to 99.1%) with the N
      gene of Araraquara hantavirus. Although the serologic method ELISA is the most
      appropriate test for HCPS diagnosis, the use of nested RT-PCR for hantavirus in
      Brazil would contribute to the diagnosis of acute hantavirus disease detecting
      viral genomes in patient specimens as well as initial genomic characterization of
      circulating hantaviruses.

PMID- 15558178
TI  - GB virus C/hepatitis G virus infection in dialysis patients and kidney transplant
      recipients in Central Brazil.
AB  - In order to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus
      (HGV) infection in dialysis patients and kidney transplant recipients in Central
      Brazil and also to analyze the virus genotypes distribution, a total of 123
      patients including 98 on hemodialysis, 13 on continuous ambulatory peritoneal
      dialysis treatment, and 12 who received kidney transplantation were interviewed
      in one unit of dialysis treatment in Goiania city. Blood samples were collected
      and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction.
      Genotypes were determined by restriction fragment length polymorphism (RFLP)
      analysis. Eighteen samples were GBV-C/HGV RNA-positive, resulting in an overall
      prevalence of 14.6% (95% CI: 9.2-21.7). A high positivity for GBV-C/HGV RNA was
      observed in patients who had received kidney transplant (16.7%), followed by
      those on hemodialysis (15.3%), and peritoneal dialysis (7.7%). RFLP analysis
      revealed the presence of genotypes 1, 2, and 3 of GBV-C/HGV; more precisely, 9
      (50%) samples were found belonging to the 2b subtype, 4 (22%) to the 2a subtype,
      3 (17%) to genotype 1, and 2 (11%) to genotype 3. The present data indicate an
      intermediate prevalence of GBV-C/HGV infection among dialysis patients and kidney
      transplant recipients in Central Brazil. Genotype 2 (subtype 2b) seems to be the
      most prevalent GBV-C/HGV genotype in our region.

PMID- 15558179
TI  - Brain natriuretic peptide and left ventricular dysfunction in chagasic
      cardiomyopathy.
AB  - Global left ventricular (LV) systolic dysfunction is the strongest predictor of
      morbidity and mortality in Chagas disease. Echocardiography is considered the
      gold standard for the detection of LV dysfunction, but not always available in
      endemic areas where chagasic cardiomyopathy is most common. Brain natriuretic
      peptide (BNP) is a neurohormone that has been recently described as a simple and
      inexpensive diagnostic and prognostic marker for patients with congestive heart
      failure. Chagasic patients (n = 63) and non-infected healthy individuals (n = 18)
      were recruited prospectively and underwent complete clinical examination,
      echocardiography and 24-h Holter monitoring. BNP was measured from thawed plasma
      samples using the Triage BNP test. We observed high levels of BNP in association
      with depression of LV ejection fraction, with increase of LV end-diastolic
      diameter and with LV premature complexes. An elevated concentration of BNP,
      defined as a concentration of 60 pg/ml or more, had a sensitivity of 91.7%,
      specificity of 82.8%, positive predictive value of 52.4%, and negative predictive
      value of 98% for detecting LV dysfunction (LV ejection fraction < 40%).BNP
      measurement using a simple, relatively inexpensive and rapid test has a promising
      role in identifying LV dysfunction associated with chagasic cardiomyopathy.
      Equally important, patients with Trypanosoma cruzi infection who have low levels
      of BNP level in plasma have a very low likelihood of severe cardiac involvement,
      and echocardiography is probably not necessary.

PMID- 15558180
TI  - Cytotoxicity of three new triazolo-pyrimidine derivatives against the plant
      trypanosomatid: Phytomonas sp. isolated from Euphorbia characias.
AB  - There is no effective chemotherapy against diseases caused by Phytomonas sp., a
      plant trypanosomatid responsible for economic losses in major crops. We tested
      three triazolo-pyrimidine complexes [two with Pt(II), and another with Ru(III)]
      against promastigotes of Phytomonas sp. isolated from Euphorbia characias. The
      incorporation of radiolabelled precursors, ultrastructural alterations and
      changes in the pattern of metabolite excretion were examined. Different degrees
      of toxicity were found for each complex: the platinum compound showed an
      inhibition effect on nucleic acid synthesis, provoking alterations on the levels
      of mitochondria, nucleus and glycosomes. These results, together with others
      reported previously in our laboratory about the activity of pyrimidine
      derivatives, reflect the potential of these compounds as agents in the treatment
      of Phytomonas sp.

PMID- 15558181
TI  - Pyrethroid insecticide evaluation on different house structures in a Chagas
      disease endemic area of the Paraguayan Chaco.
AB  - Insecticide effects of deltamethrin 2.5% SC (flowable solution) on different
      substrates and triatomine infestation rates in two indigenous villages (Estancia
      Salzar and Nueva Promesa) of the Paraguayan Chaco are reported. This field study
      was carried out to determine the extent to which variability in spray penetration
      may affect residual action of the insecticide. A total of 117 houses in the two
      villages were sprayed. Filter papers discs were placed on aluminium foil pinned
      to walls and roofs in selected houses and the applied insecticide concentration
      was determined by high pressure liquid chromatography (HPLC). The target dose
      rate was 25 mg a.i./m2. The mean actual applied dose in Estancia Salazar was 11.2
      +/- 3.1 mg a.i./m2 in walls and 11.9 +/- 5.6 mg a.i./m2 in roofs while in Nueva
      Promesa, where duplicates were carried out, the mean values were 19.9 +/- 6.9 mg
      a.i./m2 and 34.7 +/- 10.4 mg a.i./m2 in walls and 28.8 +/- 19.2 mg a.i./m2 and
      24.9 +/- 21.8 mg a.i./m2 in roofs. This shows the unevenness and variability of
      applied doses during spraying campaigns, and also the reduced coverage over roof
      surfaces. However, wall bioassays with Triatoma infestans nymphs in a 72 h
      exposure test showed that deposits of deltamethrin persisted in quantities
      sufficient to kill triatomines until three months post spraying. Knockdown by
      deltamethrin on both types of surfaces resulted in 100% final mortality. A lower
      insecticidal effect was observed on mud walls. However, three months after
      treatment, sprayed lime-coated mud surfaces displayed a twofold greater capacity
      (57.5%) to kill triatomines than mud sprayed surfaces (25%). Re-infestation was
      detected by manual capture only in one locality, six months after spraying.

PMID- 15558182
TI  - A role for histone-like protein H1 (H-NS) in the regulation of hemolysin
      expression by Serratia marcescens.
AB  - The histone-like protein H1 (H-NS) is an abundant structural component of the
      bacterial nucleoid and influences many cellular processes including
      recombination, transcription and transposition. Mutations in the hns gene
      encoding H-NS are highly pleiotropic, affecting the expression of many unrelated
      genes. We have studied the role of H-NS on the regulation of hemolysin gene
      expression in Serratia marcescens. The Escherichia coli hns mutant carrying S.
      marcescens hemolysin genes on a plasmid constructed by ligation of the 3.2-kb
      HindIII-SacI fragment of pR02 into pBluescriptIIKS, showed a high level of
      expression of this hemolytic factor. To determine the osmoregulation of wild-type
      and hns defective mutants the cells were grown to mid-logarithmic phase in LB
      medium with 0.06 or 0.3 M NaCl containing ampicillin and kanamycin, whereas to
      analyze the effect of pH on hemolysin expression, the cells were grown to late
      logarithmic phase in LB medium buffered with 0.1 M Tris-HCl, pH 4.5 to 8.0. To
      assay growth phase-related hemolysin production, bacterial cells were grown in LB
      medium supplemented with ampicillin and kanamycin. The expression of S.
      marcescens hemolysin genes in wild-type E. coli and in an hns-defective
      derivative at different pH and during different growth phases indicated that, in
      the absence of H-NS, the expression of hemolysin did not vary with pH changes or
      growth phases. Furthermore, the data suggest that H-NS may play an important role
      in the regulation of hemolysin expression in S. marcescens and its effect may be
      due to changes in DNA topology influencing transcription and thus the amount of
      hemolysin expression. Implications for the mechanism by which H-NS influences
      gene expression are discussed.

PMID- 15558183
TI  - Category fluency test: effects of age, gender and education on total scores,
      clustering and switching in Brazilian Portuguese-speaking subjects.
AB  - Verbal fluency tests are used as a measure of executive functions and language,
      and can also be used to evaluate semantic memory. We analyzed the influence of
      education, gender and age on scores in a verbal fluency test using the animal
      category, and on number of categories, clustering and switching. We examined 257
      healthy participants (152 females and 105 males) with a mean age of 49.42 years
      (SD = 15.75) and having a mean educational level of 5.58 (SD = 4.25) years. We
      asked them to name as many animals as they could. Analysis of variance was
      performed to determine the effect of demographic variables. No significant effect
      of gender was observed for any of the measures. However, age seemed to influence
      the number of category changes, as expected for a sensitive frontal measure,
      after being controlled for the effect of education. Educational level had a
      statistically significant effect on all measures, except for clustering. Subject
      performance (mean number of animals named) according to schooling was:
      illiterates, 12.1; 1 to 4 years, 12.3; 5 to 8 years, 14.0; 9 to 11 years, 16.7,
      and more than 11 years, 17.8. We observed a decrease in performance in these five
      educational groups over time (more items recalled during the first 15 s, followed
      by a progressive reduction until the fourth interval). We conclude that education
      had the greatest effect on the category fluency test in this Brazilian sample.
      Therefore, we must take care in evaluating performance in lower educational
      subjects.

PMID- 15558184
TI  - Genetic variability of hepatitis A virus isolates in Rio de Janeiro: implications
      for the vaccination of school children.
AB  - The epidemiology of hepatitis A virus (HAV) infection is shifting from high to
      intermediate endemicity in Brazil, resulting in increased numbers of susceptible
      individuals and a greater potential for the emergence of outbreaks. Universal
      vaccination against HAV has been recommended for children, but updated sero
      epidemiological data are necessary to analyze the level of natural immunity and
      to identify candidates for preventive measures. In addition, more molecular
      studies are necessary to characterize the genotypes involved in HAV infections
      and outbreaks. Sera from 299 school children (5-15 years old) and 25 school staff
      members, collected during an outbreak of HAV at a rural public school in June
      2000, were tested for IgM and total anti-HAV antibodies (ELISA). Viral RNA was
      amplified by RT-PCR from anti-HAV IgM-positive sera and from 19 fecal samples.
      Direct nucleotide sequencing of the VP1/2A region was carried out on 18 PCR
      positive samples. Acute HAV infection was detected by anti-HAV IgM in 93/299
      children and in 3/25 adult staff members. The prevalence of total anti-HAV
      antibodies in IgM-negative children under 5 years of age was only 10.5%. HAV-RNA
      was detected in 46% IgM-positive serum samples and in 16% stool samples. Sequence
      analysis showed that half the isolates belonged to subgenotype IA and the other
      half to IB. On the basis of these data, mass vaccination against HAV is
      recommended without prevaccination screening, especially for children before they
      enter school, since nearly 90% of the children under 5 years were susceptible.
      Molecular characterization indicated the endemic circulation of specific HAV
      strains belonging to subgenotypes IA and IB.

PMID- 15558185
TI  - Rarity of DNA sequence alterations in the promoter region of the human androgen
      receptor gene.
AB  - The human androgen receptor (AR) gene promoter lies in a GC-rich region
      containing two principal sites of transcription initiation and a putative Sp1
      protein-binding site, without typical "TATA" and "CAAT" boxes. It has been
      suggested that mutations within the 5'untranslated region (5'UTR) may contribute
      to the development of prostate cancer by changing the rates of gene transcription
      and/or translation. In order to investigate this question, the aim of the present
      study was to search for the presence of mutations or polymorphisms at the AR
      5'UTR in 92 prostate cancer patients, where histological diagnosis of
      adenocarcinoma was established in specimens obtained from transurethral resection
      or after prostatectomy. The AR-5'UTR was amplified by PCR from genomic DNA
      samples of the patients and of 100 healthy male blood donors, included as
      controls. Conformation-sensitive gel electrophoresis was used for DNA sequence
      alteration screening. Only one band shift was detected in one individual from the
      blood donor group. Sequencing revealed a new single nucleotide deletion (T) in
      the most conserved portion of the promoter region at position +36 downstream from
      the transcription initiation site I. Although the effect of this specific
      mutation remains unknown, its rarity reveals the high degree of sequence
      conservation of the human androgen promoter region. Moreover, the absence of
      detectable variation within the critical 5'UTR in prostate cancer patients
      indicates a low probability of its involvement in prostate cancer etiology.

PMID- 15558186
TI  - Gene expression in IFN-gamma-activated murine macrophages.
AB  - Macrophages are critical for natural immunity and play a central role in specific
      acquired immunity. The IFN-gamma activation of macrophages derived from A/J or
      BALB/c mice yielded two different patterns of antiviral state in murine hepatitis
      virus 3 infection, which were related to a down-regulation of the main virus
      receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we
      were able to identify several genes that are differently up- or down-regulated by
      IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated) or
      BALB/c (297 and 58 genes, respectively, up- and down-regulated) mouse
      macrophages. Macrophages from mice with different genetic backgrounds behave
      differently at the molecular level and comparison of the patterns of non
      activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for
      instance, an up-regulation and a down-regulation of genes coding for biological
      functions such as enzymatic reactions, nucleic acid synthesis and transport,
      protein synthesis, transport and metabolism, cytoskeleton arrangement and
      extracellular matrix, phagocytosis, resistance and susceptibility to infection
      and tumors, inflammation, and cell differentiation or activation. The present
      data are reported in order to facilitate future correlation of
      proteomic/transcriptomic findings as well as of results obtained from a classical
      approach for the understanding of biological phenomena. The possible implication
      of the role of some of the gene products relevant to macrophage biology can now
      be further scrutinized. In this respect, a down-regulation of the main murine
      hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated
      macrophages of resistant mice.

PMID- 15558187
TI  - The maternal JAK/STAT pathway of Drosophila regulates embryonic dorsal-ventral
      patterning.
AB  - Activation of NFkappaB plays a pivotal role in many cellular processes such as
      inflammation, proliferation and apoptosis. In Drosophila, nuclear translocation
      of the NFkappaB-related transcription factor Dorsal is spatially regulated in
      order to subdivide the embryo into three primary dorsal-ventral (DV) domains: the
      ventral presumptive mesoderm, the lateral neuroectoderm and the dorsal ectoderm.
      Ventral activation of the Toll receptor induces degradation of the IkappaB
      related inhibitor Cactus, liberating Dorsal for nuclear translocation. In
      addition, other pathways have been suggested to regulate Dorsal. Signaling
      through the maternal BMP member Decapentaplegic (Dpp) inhibits Dorsal
      translocation along a pathway parallel to and independent of Toll. In the present
      study, we show for the first time that the maternal JAK/STAT pathway also
      regulates embryonic DV patterning. Null alleles of loci coding for elements of
      the JAK/STAT pathway, hopscotch (hop), marelle (mrl) and zimp (zimp), modify
      zygotic expression along the DV axis. Genetic analysis suggests that the JAK
      kinase Hop, most similar to vertebrate JAK2, may modify signals downstream of
      Dpp. In addition, an activated form of Hop results in increased levels of Cactus
      and Dorsal proteins, modifying the Dorsal/Cactus ratio and consequently DV
      patterning. These results indicate that different maternal signals mediated by
      the Toll, BMP and JAK/STAT pathways may converge to regulate NFkappaB activity in
      Drosophila.

PMID- 15558188
TI  - Desmin: molecular interactions and putative functions of the muscle intermediate
      filament protein.
AB  - Desmin is the intermediate filament (IF) protein occurring exclusively in muscle
      and endothelial cells. There are other IF proteins in muscle such as nestin,
      peripherin, and vimentin, besides the ubiquitous lamins, but they are not unique
      to muscle. Desmin was purified in 1977, the desmin gene was characterized in
      1989, and knock-out animals were generated in 1996. Several isoforms have been
      described. Desmin IFs are present throughout smooth, cardiac and skeletal muscle
      cells, but can be more concentrated in some particular structures, such as dense
      bodies, around the nuclei, around the Z-line or in costameres. Desmin is up
      regulated in muscle-derived cellular adaptations, including conductive fibers in
      the heart, electric organs, some myopathies, and experimental treatments with
      drugs that induce muscle degeneration, like phorbol esters. Many molecules have
      been reported to associate with desmin, such as other IF proteins (including
      members of the membrane dystroglycan complex), nebulin, the actin and tubulin
      binding protein plectin, the molecular motor dynein, the gene regulatory protein
      MyoD, DNA, the chaperone alphaB-crystallin, and proteases such as calpain and
      caspase. Desmin has an important medical role, since it is used as a marker of
      tumors' origin. More recently, several myopathies have been described, with
      accumulation of desmin deposits. Yet, after almost 30 years since its
      identification, the function of desmin is still unclear. Suggested functions
      include myofibrillogenesis, mechanical support for the muscle, mitochondrial
      localization, gene expression regulation, and intracellular signaling. This
      review focuses on the biochemical interactions of desmin, with a discussion of
      its putative functions.

PMID- 15558189
TI  - Conventional cytogenetic characterization of a new cell line, ACP01, established
      from a primary human gastric tumor.
AB  - Gastric cancer is the second most frequent type of neoplasia and also the second
      most important cause of death in the world. Virtually all the established cell
      lines of gastric neoplasia were developed in Asian countries, and western
      countries have contributed very little to this area. In the present study we
      describe the establishment of the cell line ACP01 and characterize it
      cytogenetically by means of in vitro immortalization. Cells were transformed from
      an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old
      male patient. This is the first gastric adenocarcinoma cell line established in
      Brazil. The most powerful application of the cell line ACP01 is in the assessment
      of cytotoxicity. Solid tumor cell lines from different origins have been treated
      with several conventional and investigational anticancer drugs. The ACP01 cell
      line is triploid, grows as a single, non-organized layer, similar to fibroblasts,
      with focus formation, heterogeneous division, and a cell cycle of approximately
      40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent
      cytogenetic alteration. These data lead us to propose a multifactorial triggering
      of gastric cancer which evolves over multiple stages involving progressive
      genetic changes and clonal expansion.

PMID- 15558190
TI  - Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and
      striatum.
AB  - We studied the effects of ethanol on concentrations of noradrenaline (NE),
      dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and
      striatum. Ethanol (2 or 4 g/kg, po, from a 20% aqueous solution) was administered
      daily to male Wistar rats (4-13 per group) for 30 days and animals were
      sacrificed 30 min or 48 h after the last administration. Monoamines were measured
      by HPLC and considered significant at P < 0.05. A 47% increase in 5-HT levels was
      observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol
      (2 and 4 g/kg) decreased DA (2114.5 +/- 126.4 and 1785.1 +/- 234.2 ng/g wet
      tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 +/- 132.1
      and 1218.8 +/- 271.7 ng/g wet tissue, respectively) levels, while the higher dose
      also decreased NE (159.8 +/- 13.5), 5-HT (228.0 +/- 46.8) and 5-hydroxy-3
      indoleacetic acid (5-HIAA, 304.4 +/- 37.2 ng/g wet tissue), in the striatum after
      a 48-h withdrawal as compared to controls (DA: 3063.9 +/- 321.3; DOPAC: 2379.6 +/
      256.0; NE: 292.8 +/- 50.2; 5-HT: 412.4 +/- 36.2; 5-HIAA: 703.9 +/- 61.4 ng/g wet
      tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66
      and 70%) and DA (50 and 36%) levels. On the other hand, increases were seen in 5
      HIAA (146 and 153%) and 5-HT (59 and 86%) levels. Ethanol (2 g/kg, po) increased
      the homovanillic acid (HVA)/DA ratio (129%) in the striatum in the 30-min
      protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h
      protocol (61%). These results indicate alterations in monoamines, mainly in the
      striatum, after chronic ethanol, which are influenced by dose and by the length
      of time after the last drug administration.

PMID- 15558191
TI  - Aurapten, a coumarin with growth inhibition against Leishmania major
      promastigotes.
AB  - Several natural compounds have been identified for the treatment of
      leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones,
      and saponins. The new compound reported here, 7-geranyloxycoumarin, called
      aurapten, belongs to the chemical class of the coumarins and has a molecular
      weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia
      febrifuga and was purified from a hexane extract starting from 407.7 g of dried
      leaves and followed by four silica gel chromatographic fractionation steps using
      different solvents as the mobile phase. The resulting compound (47 mg) of shows
      significant growth inhibition with an LD50 of 30 microM against the tropical
      parasite Leishmania major, which causes severe clinical manifestations in humans
      and is endemic in the tropical and subtropical regions. In the present study, we
      investigated the atomic structure of aurapten in order to determine the existence
      of common structural motifs that might be related to other coumarins and
      potentially to other identified inhibitors of Leishmania growth and viability.
      This compound has a comparable inhibitory activity of other isolated molecules.
      The aurapten is a planar molecule constituted of an aromatic system with electron
      delocalization. A hydrophobic side chain consisting of ten carbon atoms with two
      double bonds and negative density has been identified and may be relevant for
      further compound synthesis.

PMID- 15558192
TI  - Effect of passive stretching on the immobilized soleus muscle fiber morphology.
AB  - The aim of the present study was to determine the effect of stretching applied
      every 3 days to the soleus muscle immobilized in the shortened position on muscle
      fiber morphology. Eighteen 16-week-old Wistar rats were used and divided into
      three groups of 6 animals each: a) the left soleus muscle was immobilized in the
      shortened position for 3 weeks; b) during immobilization, the soleus was
      stretched for 40 min every 3 days; c) the non-immobilized soleus was only
      stretched. Left and right soleus muscles were examined. One portion of the soleus
      was frozen for histology and muscle fiber area evaluation, while the other
      portion was used to identify the number and length of serial sarcomeres.
      Immobilized muscles (group A) showed a significant decrease in weight (44 +/-
      6%), length (19 +/- 7%), serial sarcomere number (23 +/- 15%), and fiber area (37
      +/- 31%) compared to the contralateral muscles (P < 0.05, paired Student t-test).
      The immobilized and stretched soleus (group B) showed a similar reduction but
      milder muscle fiber atrophy compared to the only immobilized group (22 +/- 40 vs
      37 +/- 31%, respectively; P < 0.001, ANOVA test). Muscles submitted only to
      stretching (group C) significantly increased the length (5 +/- 2%), serial
      sarcomere number (4 +/- 4%), and fiber area (16 +/- 44%) compared to the
      contralateral muscles (P < 0.05, paired Student t-test). In conclusion,
      stretching applied every 3 days to immobilized muscles did not prevent the muscle
      shortening, but reduced muscle atrophy. Stretching sessions induced hypertrophic
      effects in the control muscles. These results support the use of muscle
      stretching in sports and rehabilitation.

PMID- 15558193
TI  - Ginseng administration protects skeletal muscle from oxidative stress induced by
      acute exercise in rats.
AB  - Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and
      plantaris muscles of acutely exercised rats after long-term administration of
      Panax ginseng extract in order to evaluate the protective role of ginseng against
      skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was
      administered orally for three months to male Wistar rats weighing 200 +/- 50 g
      before exercise and to non-exercised rats (N = 8/group). The results showed a
      membrane stabilizing capacity of the extract since mitochondrial function
      measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase
      activities was reduced, on average, by 20% (P < 0.05) after exercise but the
      activities remained unchanged in animals treated with a ginseng dose of 100
      mg/kg. Glutathione status did not show significant changes after exercise or
      treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels,
      was significantly higher in all muscles after exercise, and again was reduced by
      about 74% (P < 0.05) by the use of ginseng extract. The administration of ginseng
      extract was able to protect muscle from exercise-induced oxidative stress
      irrespective of fiber type.

PMID- 15558194
TI  - Photocytotoxicity of a 5-nitrofuran-ethenyl-quinoline antiseptic (Quinifuryl) to
      P388 mouse leukemia cells.
AB  - Quinifuryl (MW 449.52), 2-(5'-nitro-2'-furanyl)ethenyl-4-[N-[4'-(N,N
      diethylamino)-1'-methylbutyl]carbamoyl] quinoline, is a water soluble
      representative of a family of 5-nitrofuran-ethenyl-quinoline drugs which has been
      shown to be highly toxic to various lines of transformed cells in the dark. In
      the present study, the toxicity of Quinifuryl to P388 mouse leukemia cells was
      compared in the dark and under illumination with visible light (390-500 nm).
      Illumination of water solutions of Quinifuryl (at concentrations ranging from
      0.09 to 9.0 microg/ml) in the presence of P388 cells resulted in its
      photodecomposition and was accompanied by elevated cytotoxicity. A significant
      capacity to kill P388 cells was detected at a drug concentration as low as 0.09
      microg/ml. The toxic effect detected at this drug concentration under
      illumination exceeded the effect observed in the dark by more than three times.
      Moreover, the general toxic effect of Quinifuryl, which included cell
      proliferation arrest, was nearly 100%. Both dose- and time-dependent toxic
      effects were measured under illumination. The LC50 value of Quinifuryl during
      incubation with P388 cells was approximately 0.45 microg/ml under illumination
      for 60 min and >12 microg/ml in the dark. We have demonstrated that the final
      products of the Quinifuryl photolysis are not toxic, which means that the short
      lived intermediates of Quinifuryl photodecomposition are responsible for the
      phototoxicity of this compound. The data obtained in the present study are the
      first to indicate photocytotoxicity of a nitroheterocyclic compound and
      demonstrate the possibility of its application as a photosensitizer drug for
      photochemotherapy.

PMID- 15558195
TI  - Calcium antagonism and the vasorelaxation of the rat aorta induced by
      rotundifolone.
AB  - The vasorelaxing activity of rotundifolone (ROT), a major constituent (63.5%) of
      the essential oil of Mentha x villosa, was tested in male Wistar rats (300-350
      g). In isolated rat aortic rings, increasing ROT concentrations (0.3, 1, 10, 100,
      300, and 500 microg/ml) inhibited the contractile effects of 1 microM
      phenylephrine and of 80 or 30 mM KCl (IC50 values, reported as means +/- SEM =
      184 +/- 6, 185 +/- 3 and 188 +/- 19 microg/ml, N = 6, respectively). In aortic
      rings pre-contracted with 1 microM phenylephrine, the smooth muscle-relaxant
      activity of ROT was inhibited by removal of the vascular endothelium (IC50 value
      = 235 +/- 7 microg/ml, N = 6). Furthermore, ROT inhibited (pD2 = 6.04, N = 6) the
      CaCl2-induced contraction in depolarizing medium in a concentration-dependent
      manner. In Ca2+-free solution, ROT inhibited 1 microM phenylephrine-induced
      contraction in a concentration-dependent manner and did not modify the phasic
      contractile response evoked by caffeine (20 mM). In conclusion, in the present
      study we have shown that ROT produces an endothelium-independent vasorelaxing
      effect in the rat aorta. The results further indicated that in the rat aorta ROT
      is able to induce vasorelaxation, at least in part, by inhibiting both: a)
      voltage-dependent Ca2 channels, and b) intracellular Ca2+ release selectively due
      to inositol 1,4,5-triphosphate activation. Additional studies are required to
      elucidate the mechanisms underlying ROT-induced relaxation.

PMID- 15558196
TI  - Analysis of five streptokinase formulations using the euglobulin lysis test and
      the plasminogen activation assay.
AB  - Streptokinase, a 47-kDa protein isolated and secreted by most group A, C and G ss
      hemolytic streptococci, interacts with and activates human protein plasminogen to
      form an active complex capable of converting other plasminogen molecules to
      plasmin. Our objective was to compare five streptokinase formulations
      commercially available in Brazil in terms of their activity in the in vitro tests
      of euglobulin clot formation and of the hydrolysis of the plasmin-specific
      substrate S-2251. Euglobulin lysis time was determined using a 96-well microtiter
      plate. Initially, human thrombin (10 IU/ml) and streptokinase were placed in
      individual wells, clot formation was initiated by the addition of plasma
      euglobulin, and turbidity was measured at 340 nm every 30 s. In the second assay,
      plasminogen activation was measured using the plasmin-specific substrate S-2251.
      Streptase was used as the reference formulation because it presented the
      strongest fibrinolytic activity in the euglobulin lysis test. The Unitinase and
      Solustrep formulations were the weakest, showing about 50% activity compared to
      the reference formulation. All streptokinases tested activated plasminogen but
      significant differences were observed. In terms of total S-2251 activity per
      vial, Streptase (75.7 +/- 5.0 units) and Streptonase (94.7 +/- 4.6 units) had the
      highest activity, while Unitinase (31.0 +/- 2.4 units) and Strek (32.9 +/- 3.3
      units) had the weakest activity. Solustrep (53.3 +/- 2.7 units) presented
      intermediate activity. The variations among the different formulations for both
      euglobulin lysis test and chromogenic substrate hydrolysis correlated with the
      SDS-PAGE densitometric results for the amount of 47-kDa protein. These data show
      that the commercially available clinical streptokinase formulations vary
      significantly in their in vitro activity. Whether these differences have clinical
      implications needs to be investigated.

PMID- 15558197
TI  - Relationship between cardiovascular dysfunction and hyperglycemia in
      streptozotocin-induced diabetes in rats.
AB  - Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular
      dysfunction beginning 5 days after STZ injection, which may reflect functional or
      structural autonomic nervous system damage. We investigated cardiovascular and
      autonomic function, in rats weighing 166 +/- 4 g, 5-7, 14, 30, 45, and 90 days
      after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure
      (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP),
      heart rate (HR), HR variability (standard deviation of the normal pulse
      intervals, SDNN), and root mean square of successive difference of pulse
      intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats
      vs control rats. Diabetes reduced resting HR from 363 +/- 12 to 332 +/- 5 bpm (P
      < 0.05) 5 to 7 days after STZ and reduced MAP from 121 +/- 2 to 104 +/- 5 mmHg (P
      = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs
      control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 +/- 0.9 to
      3.4 +/- 0.4 ms, P = 0.04 and SDMMAP from 6.6 +/- 0.6 to 4.2 +/- 0.6 mmHg, P =
      0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and 
      0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P <
      0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early
      in the course of diabetes, their autonomic function was reduced only 30-45 days
      after STZ injection and these changes were negatively correlated with plasma
      glucose, suggesting a metabolic origin.

PMID- 15558198
TI  - Changes in the fecal concentrations of cortisol and androgen metabolites in
      captive male jaguars (Panthera onca) in response to stress.
AB  - In the present study we determined the efficacy of the measurement of fecal
      cortisol and androgen metabolite concentrations to monitor adrenal and testicular
      activity in the jaguar (Panthera onca). Three captive male jaguars were
      chemically restrained and electroejaculated once or twice within a period of two
      months. Fecal samples were collected daily for 5 days before and 5 days after the
      procedure and stored at -20 degrees C until extraction. Variations in the
      concentrations of cortisol and androgen metabolites before and after the
      procedure were determined by solid phase cortisol and testosterone
      radioimmunoassay and feces dry weight was determined by drying at 37 degrees C
      for 24 h under vacuum. On four occasions, fecal cortisol metabolite levels were
      elevated above baseline (307.8 +/- 17.5 ng/g dry feces) in the first fecal sample
      collected after the procedure (100 to 350% above baseline). On one occasion, we
      did not detect any variation. Mean (+/- SEM) fecal androgen concentration did not
      change after chemical restraint and electroejaculation (before: 131.1 +/- 26.7,
      after: 213.7 +/- 43.6 ng/g dry feces). These data show that determination of
      fecal cortisol and androgen metabolites can be very useful for a noninvasive
      assessment of animal well-being and as a complement to behavioral, physiological,
      and pathological studies. It can also be useful for the study of the relationship
      between adrenal activity and reproductive performance in the jaguar.

PMID- 15558199
TI  - Swimming training increases cardiac vagal activity and induces cardiac
      hypertrophy in rats.
AB  - The effect of swimming training (ST) on vagal and sympathetic cardiac effects was
      investigated in sedentary (S, N = 12) and trained (T, N = 12) male Wistar rats
      (200-220 g). ST consisted of 60-min swimming sessions 5 days/week for 8 weeks,
      with a 5% body weight load attached to the tail. The effect of the autonomic
      nervous system in generating training-induced resting bradycardia (RB) was
      examined indirectly after cardiac muscarinic and adrenergic receptor blockade.
      Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry.
      Plasma catecholamine concentrations and citrate synthase activity in soleus
      muscle were also determined in both groups. Resting heart rate was significantly
      reduced in T rats (355 +/- 16 vs 330 +/- 20 bpm). RB was associated with a
      significantly increased cardiac vagal effect in T rats (103 +/- 25 vs 158 +/- 40
      bpm), since the sympathetic cardiac effect and intrinsic heart rate were similar
      for the two groups. Likewise, no significant difference was observed for plasma
      catecholamine concentrations between S and T rats. In T rats, left ventricle
      weight (13%) and myocyte dimension (21%) were significantly increased, suggesting
      cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly
      increased by 52% in T rats, indicating endurance conditioning. These data suggest
      that RB induced by ST is mainly mediated parasympathetically and differs from
      other training modes, like running, that seems to mainly decrease intrinsic heart
      rate in rats. The increased cardiac vagal activity associated with ST is of
      clinical relevance, since both are related to increased life expectancy and
      prevention of cardiac events.

PMID- 15558200
TI  - European lecture.

PMID- 15558201
TI  - [Neurosurgical treatment of acoustic neuromas without indication for
      radiosurgery].
AB  - The aim of this paper is to review the specific problems of the microsurgical
      management of the acoustic neuromas not suitable for radiosurgical treatment ,
      that is measuring more than 8 cc in volume or 2.5 cm in maximum diameter in the
      cerebelopontine angle. A total of 18 lesions have been included with a mean
      volume of 27.4 cc, representing a lesion measuring 3.8 cm in its three main
      diameters. The mean follow-up has been 48.7 months. There has been no mortality.
      All lesions were completely excised without recurrences. The anatomic
      conservation of the facial nerve was achieved in the 66.7% of the cases but the
      functional recovery (House-Brackmann grades I-II) was reached only in the 27.8%,
      without any grade I case. As permanent deficit all patients had postoperative
      cophosis, two had trigeminal hyposthesia with corneal anesthesia and one had a
      cerebellar deficit. The main conclussion is that the microsurgical radical
      resection of large acoustic neuromas not suitable for radiosurgical treatment is
      followed by a high postoperative morbidity mainly related with the facial nerve
      lesion. Therefore, it seems rationale to design specific strategies directed to
      reduce and alleviate these permanent deficits.

PMID- 15558202
TI  - [Outcome assessment in lumbar spine surgery: the patient's perspective].
AB  - At present, there is an increasing interest in evaluating the outcome of lumbar
      spinal surgery from the patient's perspective. For this purpose, numerous self
      report questionnaires for patients have been developed during last two decades.
      Recently, a core set of five domains has been recommended by an international
      panel of experts in order to assess patients with back pain: pain intensity and
      frequency, back specific function, general health status, work status and patient
      satisfaction. Also, several specific questionnaires to measure these domains,
      such as the Oswestry Disability Index, the Roland-Morris Disability
      Questionnaire, or the Short-Form 36, have been selected. In this paper,
      information about elementary features, properties and interpretation of these
      questionnaires, as well as recommendations of the international panel, are
      provided. Some adaptations to these statements for use in our country are
      suggested. In the discussion advantages, disadvantages and controversies related
      to the employment of questionnaires, and the need of further research on this
      field, are emphasized.

PMID- 15558203
TI  - Unruptured dural arteriovenous malformation of the transverse-sigmoid sinus
      presenting with focal symptoms and coma.
AB  - We are presenting the case of a 63 year-old man with a dural arteriovenous
      malformation of the transverse sigmoid sinus who developed focal deficits
      followed by less localized symptoms such a disorientation, lethargy and
      eventually comatose status. Initial cerebral angiography showed retrograde
      filling of the cortical and deep cerebral venous system with marked delay in
      venous empting. Following embolization clinical symptoms completely cleared at
      the time that control angiography showed retrograde venous flow turning
      anterograde. Patient's symptoms recurred four months later when there was a
      relapse of retrograde cerebral venous drainage at the time he developed
      thrombosis of the superior longitudinal and right transverse sinuses. Sinus
      thrombosis and thrombosis of the central retinal artery were coincidental with
      hypercoagulability related to hyperhomocysteinemia. Since control angiography
      still showed persistence of the AV shunting radical excision of the involved
      dural sinuses was performed. The final outcome was excellent. The
      physiopathological mechanism responsible for neurological deficits in our patient
      most likely was ischemia of venous origin secondary to venous hypertension
      resulting from retrograde cerebral venous drainage. The clinical and angiographic
      presentation in few similar cases reported in the literature is reviewed.

PMID- 15558204
TI  - [Contralateral extradural hematoma during evacuation of a previous one].
AB  - The development of an extradural hematoma during the evacuation of a traumatic
      extracerebral hematoma is a very rare event. It occurs in patients with a severe
      head injury that present with both an extraaxial hematoma and a contralateral
      skull fracture. Recognition of the significance of a sudden increase in the
      cerebral tension after hematoma evacuation is the key for a pront diagnosis of
      the development of a contralateral lesion. We present the case of a patient with
      a severe head trauma and an extradural hematoma who developed a contralateral
      extradural hematoma during evacuation of the initial one. The development of a
      contralateral lesion was suspected by a sudden and unexpected increase in
      cerebral tension during evacuation of the first hematoma and confirmed by
      emergency CT scan. We think that the most important pathogenetic mechanisms
      involved in the development of a contralateral extradural hematoma are the rapid
      fall of intracranial pressure, the loss of tamponade effect achieved by the
      energetic use of antiedema measures and the evacuation of the ipsilateral
      hematoma.

PMID- 15558205
TI  - [Delayed brain abscess as a complication of a CSF shunt].
AB  - INTRODUCTION: Infection is a common complication of ventriculoperitoneal shunts,
      but the formation of a brain abscess related to shunt system is very rare. We
      present the case of a patient who developed a brain abscess around a ventricular
      catheter left in place after removing the valvular system. CASE REPORT: This 38
      years old woman, underwent ventriculoperitoneal shunting for hydrocephalus
      secondary to an acoustic neurinoma. During a period of thirteen years she
      suffered two episodes of meningitis, and after the second one the CSF shunt was
      removed excepting for the ventricular catheter which appeared to be adherent to
      the choroid plexus. One year later, a brain abscess arised around that catheter,
      and both the abscess and the catheter were removed (Proteus mirabilis was the
      cultured germ). DISCUSSION: In spite of the risks related to removal of a
      proximal catheter adherent to the choroid plexus, the risk linked to the removal
      of a ventricular catheter must be counterbalanced with the risk of infection.

PMID- 15558206
TI  - [Congenital absence of a cervical spine pedicle. Incidental finding in patient
      with cervical pain. Diagnostic approach by helical CT].
AB  - Congenital absence of a cervical pedicle is usually an incidental finding in
      radiological studies made after trauma in patients with cervical pain. We report
      the case of a patient with congenital absence of the right pedicle in a cervical
      vertebra. Recognition of this anomaly is important to avoid confusion with more
      clinically significant anomalies, such as unilateral facet dislocation, that may
      result in inappropriate surgical intervention.

PMID- 15558207
TI  - [Occipital dermal sinus associated to a cerebellar abscess. Case].
AB  - Congenital dermal sinuses are tubular tracts which communicate the skin with
      deeper structures. It is a manifestation of defective separation of the ectoderm
      and neuroderm. The incidence is 1/2500-3000 births alive. Almost 10 % of
      congenital dermal sinuses are localized in the occipitocervical region. They are
      usually asymptomatic, unless an infectious process is concurrent (meningitis,
      abscess). We are presenting the case of a 12 months girl with unnoticed cutaneous
      stigmata in the occipital region, who was admitted with a meningeal syndrome and
      secondary neurological impairment. She had a cerebellar abscess and was treated
      with decompression by puncture of the abscess and antibiotics. When infection was
      resolved, congenital dermal sinus was excised. Process solves without morbidity.
      We reviewed the clinical and therapeutic features in cases reported previously in
      the literature.

PMID- 15558208
TI  - [Spontaneous spinal cord herniation].
AB  - Spontaneous spinal cord herniation through a dural defect is an unusual
      condition. This entity has been probably underestimated before the introduction
      of MRI. We report a case of a 49-year-old man with a progressive Brown-Sequard
      syndrome. MRI and CT myelogram showed a ventrally displaced spinal cord at level
      T6-T7 and expansion of the posterior subarachnoid space. Through a laminectomy, a
      spinal cord herniation was identified and reduced. The anterior dural defect was
      repaired with a patch of lyophilized dura. The patient recovered muscle power but
      there was no improvement of the sensory disturbance. The diagnosis of spontaneous
      spinal cord herniation must be considered when progressive myelopathy occurs in
      middle-aged patients, without signs of spinal cord compression and typical
      radiological findings. Surgical treatment may halt the progressive deficits and
      even yield improvement in many cases.

PMID- 15558209
TI  - The staphylocoagulase family of zymogen activator and adhesion proteins.
AB  - Staphylocoagulase (SC) secreted by Staphylococcus aureus is a potent non
      proteolytic activator of the blood coagulation zymogen prothrombin and the
      prototype of a newly established zymogen activator and adhesion protein (ZAAP)
      family. The conformationally activated SC.prothrombin complex specifically
      cleaves fibrinogen to fibrin, which propagates the growth of bacteria-fibrin
      platelet vegetations in acute bacterial endocarditis. Our recent 2.2 A X-ray
      crystal structures of an active SC fragment [SC(1-325)] bound to the prothrombin
      zymogen catalytic domain, prethrombin 2, demonstrated that SC(1-325) represents a
      new type of non-proteolytic activator with a unique fold. The observed insertion
      of the SC(1-325) N-terminus into the 'Ile 16' cleft of prethrombin 2, which
      triggers the activating conformational change, provided the first unambiguous
      structural evidence for the 'molecular sexuality' mechanism of non-proteolytic
      zymogen activation. Based on the SC(1-325) fold, a new family of bifunctional
      zymogen activator and adhesion proteins was identified that possess N-terminal
      domains homologous to SC(1-325) and C-terminal domains that mediate adhesion to
      plasma or extracellular matrix proteins. Further investigation of the ZAAP family
      may lead to new insights into the mechanisms of bacterial factors that hijack
      zymogens of the human blood coagulation and fibrinolytic systems to promote and
      disseminate endocarditis and other infectious diseases.

PMID- 15558210
TI  - Mitochondrial DNA mutators.
AB  - In this article we review our current knowledge of the mechanisms by which point
      mutations arise in the mitochondrial DNA (mtDNA) of Saccharomyces cerevisiae and
      discuss to what extent these mechanisms operate in human mtDNA mutagenesis. The
      3'-5' exonuclease proofreading activity of Pol gamma ensures accuracy of mtDNA
      replication in both yeast and humans, while the role of base excision repair in
      mtDNA error avoidance remains debated. The mitochondrial mismatch repair Msh1
      protein, which removes transitions in yeast, is absent in humans, a particularity
      that might cause accumulation of transitions, while the most frequent
      substitution in yeast mtDNA is A:T to T:A transversion. Proofreading-deficient
      mutator human cell lines and knockin mice have been created. They will be useful
      for studying the mechanisms by which mtDNA mutations accumulate in diseases,
      ageing, malignancy and drug therapy.

PMID- 15558211
TI  - Cellular microbiology of intracellular Salmonella enterica: functions of the type
      III secretion system encoded by Salmonella pathogenicity island 2.
AB  - The facultative intracellular pathogen Salmonella enterica resides in a special
      membrane compartment of the host cell and modifies its host to achieve
      intracellular survival and proliferation. The type III secretion system encoded
      by Salmonella pathogenicity island 2 (SPI2) has a central role in the
      interference of intracellular Salmonella with host cell functions. SPI2 function
      affects antimicrobial defense mechanisms of the host, intracellular transport
      processes, integrity and function of the cytoskeleton and host cell death. These
      modifications are mediated by translocation of a large number of effector
      proteins by the SPI2 system. In this review, we summarize recent work on the
      cellular phenotypes related to SPI2 function and contribution of SPI2 effector
      proteins to these manipulations. These studies reveal a complex set of pathogenic
      interferences between intracellular Salmonella and its host cells.

PMID- 15558212
TI  - Metallo-beta-lactamases: two binding sites for one catalytic metal ion?
AB  - During the past few years the results from molecular biological, biochemical,
      chemical, physical and theoretical approaches expanded the knowledge about
      metallo-beta-lactamases considerably. The main reason for the attracted interest
      is a persisting medical problem. Bacteria expressing metallo-beta-lactamases can
      be resistant to treatment with all the known beta-lactam antibiotics, and they
      are additionally invulnerable to combined treatment with inhibitors for the wider
      spread serine-beta-lactamases. However, clinically useful inhibitors for metallo
      beta-lactamases are not yet available. In spite of the rapidly expanding
      knowledge base a central question is still controversially discussed: is it the
      mononuclear, the binuclear or the metal-free state which might serve as the
      physiologically relevant target for inhibitor design? A summary of the present
      views of the roles and coordination geometries of metal ion(s) in metallo-beta
      lactamases is combined with a discussion of the possibly variable metal ion
      content under physiological conditions.

PMID- 15558213
TI  - Regulation and interactions in the activation of cell-associated plasminogen.
AB  - The main components in plasminogen activation include plasminogen, tissue
      plasminogen activator (tPA), urokinase plasminogen activator (uPA), urokinase
      plasminogen activator receptor (uPAR), and plasminogen activator inhibitors-1 and
      -2 (PAI-1, PAI-2). These components are subject to extensive regulation and
      interactions with for example, pericellular adhesion molecules. Although uPA and
      tPA are quite similar in structure and have common inhibitors and physiological
      substrates, their physiological roles are distinct. Traditionally, the role of
      tPA has been in fibrinolysis and that of uPA in cell migration, especially in
      cancer cells. Recently several targets for tPA/plasmin have been found in
      neuronal tissues. The functional role of the PAIs is no longer simply to inhibit
      overexpressed plasminogen activators, and PAI-2 has an unidentified role in the
      regulation of cell death.

PMID- 15558214
TI  - Anthrax lethal toxin: a weapon of multisystem destruction.
AB  - Lethal toxin (LT) is a major virulence factor secreted by anthrax bacteria. It is
      composed of two proteins, PA (protective antigen) and LF (lethal factor). PA
      transports the LF inside the cell, where LF, a zinc-dependent metalloprotease
      cleaves the mitogen activated protein kinase kinase (MAPKK) enzymes of the
      mitogen activated protein kinase (MAPK) signaling pathway, thereby impairing
      their function. This disruption of the MAPK pathway, which serves essential
      functions such as proliferation, survival and inflammation in all cell types,
      results in multisystem dysfunction in the host. The inactivation of the MAPK
      pathway in both macrophages and dendritic cells leads to inhibition of
      proinflammatory cytokine secretion, downregulation of costimulatory molecules
      such as CD80 and CD86, and ineffective T cell priming. The net result is an
      impaired innate and adaptive immune response. Endothelial cells of the vascular
      system undergo apoptosis upon LT exposure, also likely due to inactivation of the
      MAPK pathway. The activity of various hormone receptors such as glucocorticoids,
      progesterone and estrogen is also blocked, due to inhibition of p38 MAPK
      phosphorylation, thus affecting the body's response to stress. The present review
      summarizes the various disarming effects of Bacillus anthracis through the use of
      a single weapon, the lethal toxin.

PMID- 15558215
TI  - Molecular cloning and characterisation of DESC4, a new transmembrane serine
      protease.
AB  - Type II transmembrane serine proteases (TTSPs) are a growing family of
      multidomain proteins. Among the TTSPs, a new subfamily of HAT/DESC1-like ( human
      airway trypsin-like protease/ differentially expressed in squamous cell carcinoma
      gene 1) proteases is emerging consisting so far of four members: DESC1-3 and HAT.
      The cDNA of a new member of this subfamily, named DESC4, was isolated from rat
      tongue tissue and characterised. Analysis of selected tissues by RT-PCR
      demonstrated expression of DESC4 in brain, colon, heart, liver, lung and tongue.
      At the cellular level, DESC4 expression is confined to epithelial cells within
      the cleft of the circumvallate papillae extending into the ducts of minor
      salivary glands, the respiratory epithelium of the nasal cavity and tear gland
      ducts of the eyes as analysed by in situ hybridisation of sensory organ tissues.
      In transfected mammalian cells, DESC4 is localised to the plasma membrane as
      shown by immunocytochemistry and subcellular fractionation experiments. Our
      results suggest that we have identified a protease that is an important
      constituent of sensory systems and other organs.

PMID- 15558216
TI  - Terrein: a new melanogenesis inhibitor and its mechanism.
AB  - Terrein is a bioactive fungal metabolite whose effects are almost unknown. In
      this study, we found for the first time that terrein has a strong hypopigmentary
      effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab.
      Treatment of Mel-Ab cells with terrein (10-100 microM) for 4 days significantly
      reduced melanin levels in a dose-dependent manner. In addition, terrein at the
      same concentration also reduced tyrosinase activity. We then investigated whether
      terrein influences the extracellular signal-regulated protein kinase (ERK)
      pathway and the expression of microphthalmia-associated transcription factor
      (MITF), which is required for tyrosinase expression. Terrein was found to induce
      sustained ERK activation and MITF down-regulation, and luciferase assays showed
      that terrein inhibits MITF promoter activity in a dose-dependent manner. To
      elucidate the correlation between ERK pathway activation and a decreased MITF
      transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was
      applied before terrein treatment and found to abrogate the terrein-induced MITF
      attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h.
      These results suggest that terrein reduces melanin synthesis by reducing
      tyrosinase production via ERK activation, and that this is followed by MITF down
      regulation.

PMID- 15558217
TI  - Upregulation of rat P23 (a member of the YjgF protein family) by fasting, glucose
      diet and fatty acid feeding.
AB  - In a previous study, we identified and purified a 99-amino-acid rat liver-kidney
      perchloric-acid-soluble 23-kDa protein (P23) which displays 30% identity with a
      highly conserved domain of heat shock proteins (HSPs), as well as an AT-rich 3'
      untranslated region, which has also been described to play a role in H70 mRNA
      life span and protein expression. An identical perchloric-acid-soluble protein
      inhibiting protein synthesis in a rabbit reticulocyte lysate system was also
      found 2 years later by another group. More recently, the novel, the YjgF, protein
      family has been described, comprising, 24 full-length homologues, including P23,
      highly conserved through evolution, and consisting of approximately 130 residues
      each and sharing a common ternary structure. Independent studies from different
      laboratories have provided various hypothetical functions for each of these
      proteins. The high degree of evolutionary conservation may suggest that these
      proteins play an important role in cellular regulation. Although the function of
      none of these proteins is known precisely, we present experimental evidence
      which, combined with the relationship to glucose-regulating protein revealed
      here, and the relationship to fatty-acid-binding protein revealed by others,
      allow us to propose a role for P23. In rat liver, P23 expression is
      developmentally regulated and modulated by dietary glucose, and its mRNA is
      induced by starvation, in the presence of fatty-acids and in 3-MeDAB-induced
      hepatomas. The mRNA encoding mouse liver P23 is also hormonally modulated in a
      mouse line AT1F8. These data indicate that P23 protein might be a key controller
      of intermediary metabolism during fasting.

PMID- 15558219
TI  - ['Clinical assistants" for administrative-organizational support of hospital
      doctors].

PMID- 15558221
TI  - [Vestibular evoked muscle potentials dependency on neural origin and the location
      of an acoustic neuroma].
AB  - INTRODUCTION: Most acoustic neuromas (AN) originate from the inferior vestibular
      nerve (IVN). Vestibular evoked myogenic potentials (VEMP) are accepted as the
      only unilateral test for the function of the sacculus and the IVN. METHODS: The
      influence of the origin from the IVN and superior vestibular nerve (SVN), and the
      position of the AN in relation to the internal auditory canal on VEMPs was
      investigated. A total of 39 patients (aged: 30-67 years, mean: 53 years) were
      examined. The VEMPs were recorded on the activated sternocleidomastoid muscle and
      averaged over 200 stimuli. Tone bursts (95 dB nHL; 500 Hz; stimulation rate 5 Hz)
      were used to generate the VEMPs. RESULTS: The exact origin of the AN from the SVN
      or the IVN could be determined intraoperatively and correlated using VEMP in 28
      patients. CONCLUSION: The origin of the AN has only a marginal influence on the
      results of VEMP measurements. The position of the AN in relation to the internal
      auditory canal seems to have more influence than the origin.

PMID- 15558222
TI  - [Oncologic visceral surgery in the elderly].
AB  - Oncology in elderly and frail patients is a subject of increasing importance due
      to demographic developments in our society. So far, patient age has been highly
      important for the indication of oncologic operations. This paradigm needs to be
      changed, since preoperative diagnostics, operative techniques, and postoperative
      intensive care have improved substantially over the past years. Reviewing the
      literature, we found that oncologic operations can be performed safely with the
      same morbidity, mortality, and length of hospital stay as with younger patients.
      Pre-existing comorbidities are the most important factor in elderly patients.
      Procedures must be safe and palliation needs to be effective more than curative
      procedures. To conclude: an surgery should always be considered in the
      therapeutic strategy for elderly and frail patients.

PMID- 15558223
TI  - Regulation of matrix metalloproteinases and their inhibitors in the left
      ventricular myocardium of patients with aortic stenosis.
AB  - Aortic stenosis (AS) results in myocyte and extracellular matrix remodeling in
      the human left ventricle (LV). The myocardial renin-angiotensin system is
      activated and collagens I and III and fibronectin accumulate. We determined the
      yet unknown regulation of enzymes that control collagen turnover, i.e., LV matrix
      metalloproteinases (MMP) and their tissue inhibitors (TIMPs) in human AS. We
      compared LV samples from AS patients undergoing elective aortic valve replacement
      (n=19) with nonused donor hearts with normal LV function (controls, n=12). MMP-2,
      MMP-9, MT1-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN),
      TIMP-1, TIMP-2, TIMP-3, and TIMP-4 mRNA were quantitated by real-time RCR. MMP-1,
      MMP-2, MMP-3, TIMP-3, TIMP-4, and EMMPRIN protein were measured by immunoblotting
      and MMP-9 and TIMP-1 protein by ELISA. Gelatinolytic MMP-2 and MMP-9 activity was
      measured by zymography. MMP-2 was increased in AS at mRNA, protein, and activity
      levels (131%, 193%, and 138% of controls). MMP-3 protein (308%) and EMMPRIN mRNA
      and protein were also upregulated (171% and 200%). In contrast, MMP-1 (37%) and
      MMP-9 mRNA, protein, and activity (26%, 21%, and 52%) were downregulated. MMP-9
      activity was inversely correlated with LV size. TIMP-1 mRNA and protein were
      decreased (55% and 73%). In contrast, TIMP-2 mRNA (358%), TIMP-3 mRNA and protein
      (145% and 249%) were increased. TIMP-4 mRNA was not altered, but TIMP-4 protein
      was upregulated to 350%. Changes were similar in AS patients with normal and
      impaired LV ejection fraction. The dysregulation of myocardial MMPs and TIMPs in
      human AS starts at an early disease stage when LV function is still normal. In
      spite of upregulation of some MMPs the balance between MMP and TIMP is shifted
      towards MMP inhibition in human AS and may contribute to collagen accumulation.

PMID- 15558224
TI  - Carotenoid-based plumage coloration predicts resistance to a novel parasite in
      the house finch.
AB  - The Hamilton-Zuk hypothesis proposes that the bright colours displayed by many
      species of birds serve as signals of individual resistance to parasites. Despite
      the popularity of this hypothesis, only one previous study has tested whether
      plumage coloration predicts how individuals respond to a disease challenge. We
      inoculated 24 male house finches (Carpodacus mexicanus) of variable plumage hue
      with a novel bacterial pathogen, Mycoplasma gallicepticum (MG). We found no
      relationship between plumage hue and time to first symptoms following
      inoculation, but we found a significant negative relationship between plumage hue
      and clearance of disease: males with redder plumage cleared MG infection
      significantly better than did males with yellower plumage. The hue of carotenoid
      based plumage coloration has been shown to be a primary criterion in female mate
      choice in the house finch. These observations suggest that one benefit to females
      for choosing redder males is obtaining mates with better resistance to parasites.

PMID- 15558225
TI  - Biomolecular rods and tubes in nanotechnology.
AB  - Biomolecules are vitally important elements in nanoscale science and also in
      future nanotechnology. Their shape and their chemical and physical functionality
      can give them a big advantage over inorganic and organic substances. While this
      becomes most obvious in proteins and peptides, with their complicated, but easily
      controlled chemistry, other biomolecular substances such as DNA, lipids and
      carbohydrates can also be important. In this review, the emphasis is on one
      dimensional molecules and on molecules that self-assemble into linear structures,
      and on their potential applications. An important aspect is that biomolecules can
      act as templates, i.e. their shape and chemical properties can be employed to
      arrange inorganic substances -- such as metals or metal compounds -- on the
      nanometre scale. In particular, rod- and tube-like nanostructures can show
      physical properties that are different from those of the bulk material, and thus
      these structures are likely to be a basis for new technology.

PMID- 15558226
TI  - [Spinal intradural tumors].
AB  - Spinal intradural tumors are uncommon lesions but may cause significant
      morbidity. In establishing the differential diagnosis for a spinal lesion,
      location, age, and the patient's clinical presentation are important. Magnetic
      resonance imaging plays a central role in the visualization of spinal tumors,
      easily allowing tumors to be classified as extradural, intradural extramedullary,
      or intramedullary which is very useful in tumor characterization. We describe
      intradural tumors; the majority is extramedullary, with nerve sheath tumors being
      the most frequent. Intramedullary tumors are uncommon spinal tumors. Ependymomas
      and astrocytomas comprise the majority of this group. Typical imaging features of
      both intradural extramedullary and intramedullary tumors are described.

PMID- 15558227
TI  - [Whole-body MRI and PET/CT in tumor diagnosis].
AB  - Tumor staging according to the TNM-system influences prognosis and therapeutical
      options of patients with a malignant disease. It is the challenge of diagnostic
      imaging to depict the exact localization of the primary tumor and to detect or
      rule out lymph node involvement or distant metastases. In doing so, the complete
      body anatomy should be covered with a modality that offers high sensitivity and
      specificity. As these requirements could not or only partially be achieved by
      previous ordinary procedures, the use of multiple different modalities became
      necessary. Last but not least, in consideration of the costs it would be
      preferable to replace this cascade of different modalities by a "whole body
      examination", preconditioned that the same accuracy is achieved.With PET/CT and
      whole-body MRI, two newly available promising methods for a systemic tumor
      staging have been developed. First experiences indicate PET/CT as a method of
      first choice. With the introduction of new whole-body MRI scanners using parallel
      imaging technique (iPAT) and free table movement, MRI plays a more and more
      important role in whole body tumor staging.

PMID- 15558228
TI  - QTL analysis and comparative genomics of herbage quality traits in perennial
      ryegrass (Lolium perenne L.).
AB  - Genetic control of herbage quality variation was assessed through the use of the
      molecular marker-based reference genetic map of perennial ryegrass (Lolium
      perenne L.). The restriction fragment length polymorphism (RFLP), amplified
      fragment length polymorphism (AFLP) and genomic DNA-derived simple sequence
      repeat-based (SSR) framework marker set was enhanced, with RFLP loci
      corresponding to genes for key enzymes involved in lignin biosynthesis and
      fructan metabolism. Quality traits such as crude protein (CP) content, estimated
      in vivo dry matter digestibility (IVVDMD), neutral detergent fibre content (NDF),
      estimated metabolisable energy (EstME) and water soluble carbohydrate (WSC)
      content were measured by near infrared reflectance spectroscopy (NIRS) analysis
      of herbage harvests. Quantitative trait locus (QTL) analysis was performed using
      single-marker regression, simple interval mapping and composite interval mapping
      approaches, detecting a total of 42 QTLs from six different sampling experiments
      varying by developmental stage (anthesis or vegetative growth), location or year.
      Coincident QTLs were detected on linkage groups (LGs) 3, 5 and 7. The region on
      LG3 was associated with variation for all measured traits across various
      experimental datasets. The region on LG7 was associated with variation for all
      traits except CP, and is located in the vicinity of the lignin biosynthesis gene
      loci xlpomt1 (caffeic acid-O-methyltransferase), xlpccr1 (cinnamoyl CoA
      reductase) and xlpssrcad 2.1 (cinnamyl alcohol dehydrogenase). Comparative
      genomics analysis of these gene classes with wheat (Triticum aestivum L.)
      provides evidence for conservation of gene order over evolutionary time and the
      basis for cross-specific genetic information transfer. The identification of co
      location between QTLs and functionally associated genetic markers is critical for
      the implementation of marker-assisted selection programs and for linkage
      disequilibrium studies, which will enable future improvement strategies for
      perennial ryegrass.

PMID- 15558229
TI  - An SSR- and AFLP-based genetic linkage map of tall fescue (Festuca arundinacea
      Schreb.).
AB  - Tall fescue (Festuca arundinacea Schreb.) is commonly grown as forage and turf
      grass in the temperate regions of the world. Here, we report the first genetic
      map of tall fescue constructed with PCR-based markers. A combination of amplified
      fragment length polymorphisms (AFLPs) and expressed sequence tag-simple sequence
      repeats (EST-SSRs) of both tall fescue and those conserved in grass species was
      used for map construction. Genomic SSRs developed from Festuca x Lolium hybrids
      were also mapped. Two parental maps were initially constructed using a two-way
      pseudo-testcross mapping strategy. The female (HD28-56) map included 558 loci
      placed in 22 linkage groups (LGs) and covered 2,013 cM of the genome. In the male
      (R43-64) map, 579 loci were grouped in 22 LGs with a total map length of 1,722
      cM. The marker density in the two maps varied from 3.61 cM (female parent) to
      2.97 (male parent) cM per marker. These differences in map length indicated a
      reduced level of recombination in the male parent. Markers that revealed
      polymorphism within both parents and showed 3:1 segregation ratios were used as
      bridging loci to integrate the two parental maps as a bi-parental consensus. The
      integrated map covers 1,841 cM on 17 LGs, with an average of 54 loci per LG, and
      has an average marker density of 2.0 cM per marker. Homoeologous relationships
      among linkage groups of six of the seven predicted homeologous groups were
      identified. Three small groups from the HD28-56 map and four from the R43-64 map
      are yet to be integrated. Homoeologues of four of those groups were detected.
      Except for a few gaps, markers are well distributed throughout the genome.
      Clustering of those markers showing significant segregation distortion (23% of
      total) was observed in four of the LGs of the integrated map.

PMID- 15558230
TI  - Use of artificial environments to reproduce and exploit genotype x location
      interaction for lucerne in northern Italy.
AB  - Genotype x environment interaction effects can be exploited by breeding for
      specific adaptation to well-defined subregions within a target region. Previous
      work showed that genotype x location interaction for dry matter (DM) yield of
      lucerne (Medicago sativa L. subsp. sativa) cultivars in northern Italy is large
      and associated with soil type and level of summer drought stress of locations,
      suggesting the presence of two contrasting subregions. Thirteen farm landraces
      collected across the region and four control varieties were evaluated for DM
      yield in four artificial environments created at one site by the factorial
      combination of soil type (sandy loam or silty clay) and drought stress level
      (almost nil or high) for: (1) exploring the possibility to reproduce in
      artificial environments the adaptation patterns occurring across the region; (2)
      investigating the adaptation pattern of landraces and its relationship with
      environmental factors at collecting sites; and (3) providing a preliminary
      comparison of wide- versus specific-adaptation strategies based on yield gains
      predicted from selection of populations. Different soils filled large
      (24.0x1.6x0.8-m deep), bottomless containers in concrete. Water amounts were
      controlled by irrigation under a moving rain shelter. Cultivars varied largely
      for adaptation pattern across the artificial environments, mainly due to cultivar
      x stress interaction. Better response to stress conditions of landraces was
      closely associated with the level of summer drought at collecting sites (r=0.82),
      highlighting the importance of evolutionary adaptation. The additive main effects
      and multiplicative interaction-modelled responses of control cultivars
      successfully reproduced those observed across locations, candidating the
      artificial environments as a cheaper alternative to more selection locations when
      breeding for wide or specific adaptation. The latter implied about 40-50% greater
      estimated gains relative to breeding for wide adaptation.

PMID- 15558231
TI  - Smoking is associated with an increased risk of type 2 diabetes but a decreased
      risk of autoimmune diabetes in adults: an 11-year follow-up of incidence of
      diabetes in the Nord-Trondelag study.
AB  - AIMS/HYPOTHESIS: We compared the association between smoking habits and later
      occurrence of type 2 diabetes on the one hand and between smoking and diabetes
      with autoimmunity on the other hand. METHODS: We used data from a prospective
      study of 11-year cumulative incidence of diabetes in the Nord-Trondelag Health
      Survey. RESULTS: Confirming previous reports, heavy smoking (>/=20 cigarettes per
      day) carried an increased relative risk (RR) of type 2 diabetes (n=738, RR=1.64,
      95% CI: 1.12-2.39). In contrast, smoking reduced the risk of latent autoimmune
      diabetes in adults (LADA) and of traditional type 1 diabetes (LADA n= 81,
      RR=0.25, 95% CI: 0.11-0.60; type 1 diabetes, n=18, RR=0.17, 95% CI: 0.04-0.73).
      CONCLUSIONS/INTERPRETATIONS: The results indicate that nicotine influences
      autoimmune processes in human diabetes.

PMID- 15558232
TI  - Monocytic expression of CD14 and CD18, circulating adhesion molecules and
      inflammatory markers in women with diabetes mellitus and impaired glucose
      tolerance.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is a major risk factor for cardiovascular
      disease. Monocyte recruitment and inflammatory activation are crucial steps in
      the development of atherosclerosis and several receptors are involved in these
      processes. The aim of this study was to investigate levels of CD14 and the
      beta(2)-integrin subunits CD11b and CD18 on monocytes from women with diabetes or
      impaired glucose tolerance. METHODS: A population-based sample of 112 Swedish
      women, who were aged 64 years and had diabetes mellitus or impaired or normal
      glucose tolerance, was investigated. Cell surface receptors were analysed with
      flow cytometry and serum inflammation markers and soluble adhesion molecules with
      enzyme-linked methods. RESULTS: The monocytic CD14 expression and serum levels of
      C-reactive protein, IL-6 and soluble adhesion molecules were higher in the
      diabetes group than in the group with normal glucose tolerance. Monocytic CD18
      was elevated both in the diabetes and in the impaired glucose tolerance groups.
      The levels of monocytic surface markers correlated with BMI and to a lesser
      extent with glycaemic control. CONCLUSIONS/INTERPRETATION: The increased
      monocytic expression of important surface receptors together with elevated serum
      inflammation markers supports the concept of increased inflammation in type 2
      diabetes and may be an important factor for the risk of atherosclerosis.

PMID- 15558233
TI  - The p75 neurotrophin receptor appears in plasma in diabetic rats-characterisation
      of a potential early test for neuropathy.
AB  - AIMS/HYPOTHESIS: This study tested the premise that immunoreactivity representing
      the p75 neurotrophin receptor (p75(NTR)) appears in plasma of diabetic rats in
      association with the early stages of neuronal dysfunction or damage. We also
      examined whether treatment beneficial to neuropathy might reduce the p75(NTR)
      immunoreactivity. METHODS: Plasma proteins were fractionated by SDS-PAGE and
      immunoblots exposed to p75(NTR) antibody, using receptor protein from cultured
      PC12 cells as an external standard. Rats were made diabetic with streptozotocin
      for various periods and exsanguinated. Plasma glucose, HbA(1)c and plasma
      proteins were determined. We also studied plasma samples from diabetic mice
      lacking the gene coding for p75(NTR), as well as the effect of sciatic nerve
      crush on healthy male Wistar rats. RESULTS: Plasma p75(NTR) immunoreactivity
      began to exceed normal levels at 8 weeks after induction of diabetes, and was
      significantly raised at 10 (p<0.05) and 12 weeks (p<0.001). Treatment between 8
      and 12 weeks with insulin, fidarestat (an aldose reductase inhibitor), nerve
      growth factor and neurotrophin 3 all normalised the plasma p75(NTR)
      immunoreactivity. Plasma from p75(NTR) (-/-) mice contained no such
      immunoreactivity, though it was present in plasma from wild-type mice. Following
      nerve crush, p75(NTR) immunoreactivity appeared in plasma of non-diabetic mice,
      indicating that this can be a result of nerve trauma. CONCLUSIONS/INTERPRETATION:
      These observations suggest that plasma p75(NTR) immunoreactivity may serve as an
      early indicator of neuronal dysfunction or damage in diabetes. The time course of
      its appearance relates well to that of early neuropathy and its response to
      interventions that are neuroprotective suggests that it might mirror neurological
      status.

PMID- 15558234
TI  - [Injectable carrier system for growth factor application in minimally invasive
      stimulation of bone healing].
AB  - The characterization and cloning of growth factors for bone healing provide an
      enormous potential for minimally invasive treatment procedures for bone defects
      or fractures. However, the clinical application of injection vehicles for these
      growth factors must be made user-friendlier. In this study, two different
      injection vehicles were tested for their practicability and efficacy to enhance
      callus maturation during distraction osteogenesis. Calcium phosphate carriers
      showed a rather low user-friendliness and were less efficient in the animal model
      of distraction osteogenesis in sheep. Collagen carriers provided both a higher
      practicability for injection procedures and a higher efficacy.

PMID- 15558235
TI  - [Tissue engineering of long bones with a vascular matrix in a bioreactor].

PMID- 15558237
TI  - Decreased bone mineral density at the distal radius, but not at the lumbar spine
      or the femoral neck, in Japanese type 2 diabetic patients.
AB  - The purpose of this study is to assess the association between type 2 diabetes
      and bone mineral density. This study included 145 Japanese patients (64 men and
      81 women) with type 2 diabetes and 95 non-diabetic control subjects (41 men and
      54 women) of similar age. We measured bone mineral density (BMD) at the sites
      with different cortical/cancellous bone ratio (lumbar spine, femoral neck, and
      distal radius) using dual-energy X-ray absorptiometry. BMD and Z score at the
      distal radius were significantly lower in type 2 diabetic patients than those in
      control subjects, and in type 2 diabetic patients, the Z score at the distal
      radius was lower than that at their own lumbar spine and femoral neck. In type 2
      diabetic patients, negative correlation between BMD and the mean HbA1c during the
      previous 2 years was found significantly at the distal radius in both genders and
      at the femoral neck in women. These results indicate the selective cortical bone
      loss in type 2 diabetes and suggest the importance of also determining BMD at the
      radius and keeping good metabolic control to prevent bone loss in type 2 diabetic
      patients.

PMID- 15558238
TI  - Impact of incident vertebral fractures on health related quality of life (HRQOL)
      in postmenopausal women with prevalent vertebral fractures.
AB  - Vertebral fractures are a common complication of osteoporosis and may cause a
      decrease of health-related quality of life (HRQOL). This study was designed to
      determine the impact of incident vertebral fractures on HRQOL. The Multiple
      Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double blind
      trial, in which women were taking raloxifene or placebo. This study was done in
      European centers only in a subset of 361 women from seven European countries, all
      with prevalent vertebral fractures. A specific questionnaire for osteoporosis
      developed by the International Osteoporosis Foundation was used for assessment at
      baseline, 1, 2 and 3 years. This questionnaire, Qualeffo, contains 41 questions
      in the domains pain, physical function, social function, general health
      perception and mental function. Domain and total scores are expressed on a 100
      point scale with 0 corresponding to the best HRQOL. Standardized lateral spinal
      radiographs were made at baseline, 2 and 3 years and evaluated in a central
      facility. Sixty-seven patients sustained a fracture in a vertebra that was not
      fractured at baseline (incident vertebral fractures). Twenty of these were
      accompanied by signs and symptoms necessitating immediate doctor's attention
      (clinical vertebral fractures) and 47 vertebral fractures were only diagnosed on
      radiographs (subclinical vertebral fractures). Incident vertebral fractures
      (clinical and subclinical) were associated with an increase of back pain (mean
      score change 6.4; 95% CI 2.1-10.7), deterioration of physical function (mean
      score change 2.4; 95% CI 0.1-4.8), and worse general health perception (mean
      score change 3.8; 95% CI 0.1-7.5). Score changes for patients with subclinical
      vertebral fractures were intermediate between those for patients with clinical
      vertebral fractures and patients without incident vertebral fracture. Clinical
      and subclinical incident vertebral fractures both have an adverse impact on
      HRQOL.

PMID- 15558239
TI  - Re-investigation of the concordance of human NAT2 phenotypes and genotypes.
AB  - A comparative study of N-acetyltransferase 2 (NAT2) genotyping and phenotyping
      (caffeine test method) was performed on 211 persons to elucidate apparent
      discrepancies in the assignment of NAT2*12 and NAT2*13 alleles which occur in the
      literature. The study used the standard procedures of genotyping (two PCR runs
      and application of seven restriction enzymes) and phenotyping (determination of
      the two caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU)
      and 1-methylxanthine (1X)), as documented in detail and validated by the Deutsche
      Forschungsgemeinschaft. The data were consistent with an AFMU/1X molar ratio of
      0.85 as cut-off point (antimode) between phenotypically slow and rapid
      acetylators. Under this provision, several R/S allele combinations did not
      comply, either fully or partly, with their associated phenotypes. In particular,
      there was a wide phenotypic overlap of the alleged rapid allele combination
      groups (i) NAT2*12A/*5A; NAT2*12C/*5D; NAT2*4/*5B, (ii) NAT2*13/*6B; NAT2*4/*6A,
      and (iii) NAT2*13/*7A; NAT2*4/*7B. These groups obviously contained both
      phenotypically rapid and slow acetylators. If one assumes that the presence of
      one "wild type" allele NAT2*4 defines a rapid acetylator the assignment of the
      alleles NAT2*12A, NAT2*12C, and NAT*13 as determinants of a rapid acetylator
      phenotype must be questioned. This refers in particular to the nucleotide changes
      A803G (NAT2*12A, NAT2*12C) and C282T (NAT2*13). Based on discussions in the
      literature and the data presented here, there is accumulating evidence that
      current assignments of the NAT2*12 and NAT2*13 alleles as determinants of a rapid
      acetylator state should be reconsidered.

PMID- 15558240
TI  - Potentiation of the teratogenic effects induced by coadministration of retinoic
      acid or phytanic acid/phytol with synthetic retinoid receptor ligands.
AB  - Previous studies in our laboratory identified retinoid-induced defects that are
      mediated by RAR-RXR heterodimerization using interaction of synthetic ligands
      selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997,
      Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol
      170:2-9; Nau and Elmazar 1999, Handbook of experimental pharmacology, vol 139,
      Retinoids, Springer-Verlag, pp 465-487). The present study was designed to
      investigate whether these RAR-RXR heterodimer-mediated defects can be also
      induced by interactions of natural and synthetic ligands for retinoid receptors.
      A non-teratogenic dose of the natural RXR agonist phytanic acid (100 mg/kg
      orally) or its precursor phytol (500 mg/kg orally) was coadministered with a
      synthetic RARalpha-agonist (Am580; 5 mg/kg orally) to NMRI mice on day 8.25 of
      gestation (GD8.25). Furthermore, a non-teratogenic dose of the synthetic RXR
      agonist LGD1069 (20 mg/kg orally) was also coadministered with the natural RAR
      agonist, all- trans-retinoic acid (atRA, 20 mg/kg orally) or its precursor
      retinol (ROH, 50 mg/kg orally) to NMRI mice on GD8.25. The teratogenic outcome
      was scored in day-18 fetuses. The incidence of Am580-induced resorptions, spina
      bifida aperta, micrognathia, anotia, kidney hypoplasia, dilated bladder,
      undescended testis, atresia ani, short and absent tail, fused ribs and fetal
      weight retardation were potentiated by coadministration of phytanic acid or its
      precursor phytol. Am580-induced exencephaly and cleft palate, which were not
      potentiated by coadministration with the synthetic RXR agonists, were also not
      potentiated by coadministration with either phytanic acid or its precursor
      phytol. LGD1069 potentiated atRA- and ROH-induced resorption, exencephaly, spina
      bifida, aperta, ear anotia and microtia, macroglossia, kidney hypoplasia,
      undescended testis, atresia ani, tail defects and fetal weight retardation, but
      not cleft palate. These results suggest that synergistic teratogenesis can be
      induced by coadministration of a natural RXR ligand (phytanic acid) with a
      synthetic RAR agonist (Am580). Thus, certain potentially useful therapeutic
      agents or nutritional factors such as phytanic acid should be tested for
      teratogenic risk by coadministration with other retinoid receptor agonists.

PMID- 15558241
TI  - Inhibitory effects of AMP 579, a novel cardioprotective adenosine A1/A2A receptor
      agonist, on native IKr and cloned HERG current.
AB  - We investigated the effects of 1S-[1a,2b,3b,4a(S*)]-4-[7-[[1-[(3-chloro-2
      thienyl)methylpropyl]propyl-amino]-3H-imidazo[4,5-b] pyridyl-3-yl]-N-ethyl-2,3
      dihydroxycyclopentane carboxamide (AMP 579), a novel cardioprotective adenosine
      A(1)/A(2A) receptor agonist, on the rapid and slow components of the delayed
      rectifier K(+) current (I(Kr) and I(Ks)) in guinea-pig ventricular myocytes and
      on the human ether-a-go-go-related gene (HERG) channel expressed in human
      embryonic kidney (HEK 293) cells. Whole-cell current and membrane potential were
      recorded using patch-clamp techniques. In guinea-pig ventricular myocytes, AMP
      579 inhibited I(Kr) in a concentration-dependent manner with IC(50) value of 15.2
      microM, when I(Kr) was blocked by chromanol 293B. On the contrary, AMP 579 (10
      microM) did not affect I(Ks) in the presence of the I(Kr) blocker E-4031. The
      former effect of AMP 579 was unaffected by either the selective adenosine A(1)
      receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or the non-selective
      adenosine A(1)/A(2) receptor antagonist 8-sulphophenyltheophylline. Moreover, AMP
      579-induced inhibition of I(Kr) was not voltage- and frequency-dependent. In HEK
      293 cells expressing HERG channels, AMP 579 (10 microM) significantly blocked the
      HERG current at +10 mV by 34.9+/-7.0% (n=4, p<0.05), and the degree of inhibition
      was comparable with that observed in guinea-pig ventricular myocytes (36.8+/
      6.0%, n=4). AMP 579 (10 microM) significantly inhibited the L-type Ca(2+) current
      (I(Ca)) by 41.0+/-6.8% (n=5, p<0.05), which was unaffected by 8-sulphophenyl
      theophylline. Consequently, despite its inhibitory actions on I(Kr) or HERG
      current, the drug significantly shortened the action potential duration measured
      at 90% repolarization from 275.6+/-19.4 to 208.3+/-18.6 ms (n=4, p<0.05). Thus,
      AMP 579 inhibits both native I(Kr) and cloned HERG channels with additional
      inhibitory effect of I(Ca), and such inhibitory effects may at least partially
      underlie the observed antifibrillatory action of the drug during myocardial
      ischemia/reperfusion.

PMID- 15558242
TI  - Stimulation of cellular free Ca2+ elevation and inhibition of store-operated Ca2+
      entry by kazinol B in neutrophils.
AB  - Kazinol B, a natural isoprenylated flavan, stimulated the [Ca(2+)](i) elevation
      in the presence or absence of Ca(2+) in the medium. Treatment with chymotrypsin
      or phorbol 12-myristate 13-acetate to shedding of L: -selectin had no effect on
      subsequent kazinol B-induced Ca(2+) response. Upon initial cyclopiazonic acid
      (CPA) treatment in the absence of external Ca(2+), the subsequent [Ca(2+)](i)
      rise followed by challenge with kazinol B was greatly diminished. The ryanodine
      receptor blockers, 8-bromo-cyclic ADP-ribose and ruthenium red did not affect
      kazinol B-evoked Ca(2+) release from internal stores. However, the inhibitors of
      sphingosine kinase, dimethylsphingosine, but not dihydrosphingosine, inhibited
      kazinol B-induced Ca(2+) release. Kazinol B-induced [Ca(2+)](i) rise was not
      affected by two nitric oxidase inhibitors, N-(3-aminomethyl)benzylacetamidine
      (1400W) and 7-nitroindazole, cytochalasin B and Na(+)-deprivation. This response
      was slightly attenuated by 2-aminoethyldiphenyl borate (2-APB), a D: -myo
      inositol 1,4,5-trisphosphate (IP(3)) receptor blocker, and by genistein, a
      general tyrosine kinase inhibitor. However, the Ca(2+) response was greatly
      diminished by two actin filament reorganizers, calyculin A and jasplakinolide, 2
      (4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY 294002), an inhibitor of
      phosphoinositide 3-kinase, N-(3-aminomethyl)benzylacetamidine (SB 203580), the
      p38 mitogen-activated protein kinase inhibitor, 1-[6-[17beta-3-methoxyestra
      1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), the inhibitor
      of phospholipase C-coupled processes, and by 0.3 mM La(3+) or Ni(2+). Kazinol B
      did not evoke any appreciable Ba(2+) and Sr(2+) entry into cells. The Ca(2+)
      entry blockers, 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H
      imidazole (SKF-96365), but not cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2
      amine (MDL-12,330A), inhibited a kazinol B-induced [Ca(2+)](i) rise. Kazinol B
      had no effect on the pharmacologically isolated plasma membrane Ca(2+)-ATPase
      activity. In a Ca(2+)-free medium, kazinol B inhibited the subsequent Ca(2+)
      addition, resulting in robust entry in CPA- and formyl peptide-activated cells.
      Kazinol B produced a concentration-dependent reduction in the mitochondrial
      membrane potential. These results indicate that kazinol B stimulates Ca(2+)
      release from internal Ca(2+) store, probably through the sphingosine 1-phosphate
      and IP(3) signaling, and activates external Ca(2+) influx mainly through a non
      store-operated Ca(2+) entry (non-SOCE) pathway. Inhibition of SOCE by kazinol B
      is probably attributable to a break in the Ca(2+) driven force of mitochondria.

PMID- 15558246
TI  - Fully automated biosensors for water analysis.

PMID- 15558243
TI  - Block of wild-type and inactivation-deficient human ether-a-go-go-related gene K+
      channels by halofantrine.
AB  - Halofantrine is an antimalarial drug developed as a treatment of P. falciparum
      resistant to chloroquine. However, halofantrine can also induce long QT syndrome
      (LQTS) and torsades de pointes, a potentially life-threatening ventricular
      arrhythmia. Drug-induced LQTS is usually caused by block of the human ether-a-go
      go-related gene (HERG) channels that conduct the rapid delayed rectifier K(+)
      current, I(Kr), in the heart. Here we show that halofantrine preferentially
      blocks open and inactivated HERG channels heterologously expressed in Xenopus
      laevis oocytes. The half-maximal inhibitory concentration (IC(50)) for block of
      wild-type (WT) HERG was 1.0 microM. As we reported previously for other HERG
      channel blockers, the potency of halofantrine was reduced by mutation to Ala of
      aromatic residues (Y652, F656) located in the S6 domain, or a Val (V625) located
      in the pore helix. Halofantrine at a concentration 10 microM did not affect the
      transient outward potassium channel, Kv4.3, the slow delayed rectifier potassium
      channel, KvLQT1+minK and inward rectifier potassium channel, Kir2.1. An
      inactivation deficient mutant (G628C/S631C HERG) was only slightly less sensitive
      (IC(50)=2.0 microM). The rate of block onset by halofantrine at 0 mV was used to
      estimate the apparent association (k(on)) and dissociation (k(off)) rate
      constants for drug binding. For WT and G628C/S631C HERG, k(on) was similar
      (0.0114 and 0.0163 M(-1)/s(-1) respectively). In contrast, k(off) was
      significantly faster for G628C/S631C (0.357 s(-1)) than WT (0.155 s(-1)), and
      explains the observed decrease in drug potency for the inactivation-deficient
      mutant channel. We conclude that halofantrine requires channels to open before it
      can gain access to its binding site located in the central cavity of the HERG
      channel.

PMID- 15558247
TI  - Preservation strategies for inorganic arsenic species in high iron, low-Eh
      groundwater from West Bengal, India.
AB  - Despite the importance of accurately determining inorganic arsenic speciation in
      natural waters to predicting bioavailability and environmental and health
      impacts, there remains considerable debate about the most appropriate species
      preservation strategies to adopt. In particular, the high-iron, low-Eh (redox
      potential) shallow groundwaters in West Bengal, Bangladesh and SE Asia, the use
      of which for drinking and irrigation purposes has led to massive international
      concerns for human health, are particularly prone to changes in arsenic
      speciation after sampling. The effectiveness of HCl and EDTA preservation
      strategies has been compared and used on variably arsenic-rich West Bengali
      groundwater samples, analysed by ion chromatography-inductively coupled plasma
      mass spectrometry (IC-ICP-MS). Immediate filtration and acidification with HCl
      followed by refrigerated storage was found to be the most effective strategy for
      minimizing the oxidation of inorganic As(III) during storage. The use of a PRP
      X100 (Hamilton) column with a 20 mmol L(-1) NH4H2PO4 as mobile phase enabled the
      separation of Cl- from As(III), monomethylarsonic acid, dimethylarsinic acid and
      As(V), thereby eliminating any isobaric interference between 40Ar35Cl+ and 75As+.
      The use of EDTA as a preservative, whose action is impaired by the high calcium
      concentrations typical of these types of groundwater, resulted in marked
      oxidation during storage. The use of HCl is therefore indicated for analytical
      methods in which chloride-rich matrices are not problematical. The groundwaters
      analysed by IC-ICP-MS were found to contain between 5 and 770 ng As mL(-1)
      exclusively as inorganic arsenic species. As(III)/total-As varied between 0 and
      0.94.

PMID- 15558248
TI  - Electrogenerated chemiluminescence on microfluidic chips.

PMID- 15558250
TI  - Facilitatory effect on the motor cortex by electrical stimulation over the
      cerebellum in humans.
AB  - Electrical stimulation over the cerebellum is known to transiently suppress the
      contralateral motor cortex in humans. However, projections from the cerebellar
      nuclei to the primary motor cortex are disynaptic excitatory pathways through the
      ventral thalamus. In the present investigation we studied facilitatory effects on
      the motor cortical excitability elicited by electrical stimulation over the
      cerebellum by recording surface electromyographic (EMG) responses from the first
      dorsal interosseous (FDI) muscle in nine normal volunteers. For primary motor
      cortical activation magnetic stimuli were given over the contralateral hand motor
      area with a figure-of-eight shaped coil with a current to preferentially elicit
      I3-waves (test stimulus). For cerebellar stimulation high-voltage electric
      stimuli were given with an anode on the ipsilateral mastoid process and a cathode
      over the contralateral process as previously described (conditioning stimulus).
      The effect of conditioning-test interstimulus intervals was investigated. Anodal
      cerebellar stimuli increased the size of EMG responses to magnetic cortical
      stimulation at an interstimulus interval of 3 ms. Reversing the current of
      conditioning stimulus abolished the facilitation. The same (anodal) conditioning
      stimuli did not affect electrically evoked cortical responses. Based on the
      effective polarity of the conditioning stimulus and the time course of
      facilitation we consider that this effect is due to motor cortical facilitation
      elicited by activation of the excitatory dentatothalamocortical pathway at the
      deep cerebellar nuclei or superior cerebellar peduncle. We conclude that the
      motor cortical facilitation is evoked by cerebellar stimulation in humans.

PMID- 15558251
TI  - Augmented visual feedback increases finger tremor during postural pointing.
AB  - Physiological tremor in the upper limb of eight adults was examined during the
      performance of a unilateral pointing task under conditions where the visual
      feedback, limb used and target size were altered. All subjects were required to
      aim a hand-held laser pointer at a circular target 5.5 m away with the goal of
      keeping the laser emission within the centre of the target. Visual feedback was
      defined as either normal vision (NV) of their limb tremor, where the laser was
      switched off, or augmented vision (AV) where the laser was switched on. Postural
      tremor from the segments of the upper limb, forearm muscle EMG activity, and
      target accuracy measures were recorded and analysed in the time and frequency
      domains. Accuracy-tremor relations were assessed using cross correlation and
      linear regression. Results revealed a high degree of similarity in the general
      pattern of the tremor output seen for each limb segment across conditions with
      only scalar (amplitude) changes being seen as a function of the different
      constraints imposed. For any single condition the tremor amplitude increased from
      proximal to distal segments. The frequency profile for the tremor in any segment
      displayed two prominent frequency peaks (at 2-4 Hz and 8-12 Hz). A third, higher
      frequency peak (18-22 Hz) was observed in the index fingers only. Across all
      conditions significant coupling relations were observed only between the hand
      finger and forearm-upper arm segment pairs. Altering the visual feedback was
      shown to have the greatest effect on limb tremor with increased tremor and EMG
      activity and decreased coupling being seen under AV conditions. In trying to
      reduce tremor output when the augmented feedback was provided novice subjects
      instead increased muscle activity which resulted in increased tremor. Overall
      these results indicate that the physiological tremor output observed in
      neurologically normal subjects is not simply the product of intrinsic
      oscillations but is influenced by the nature of the task being performed.

PMID- 15558252
TI  - Role of across-muscle motor unit synchrony for the coordination of forces.
AB  - Evidence from five-digit grasping studies indicates that grip forces exerted by
      pairs of digits tend to be synchronized. It has been suggested that motor unit
      synchronization might be a mechanism responsible for constraining the temporal
      relationships between grip forces. To evaluate this possibility and quantify the
      effect of motor unit synchrony on force relationships, we used a motor unit model
      to simulate force produced by two muscles using three physiological levels of
      motor unit synchrony across the two muscles. In one condition, motor units in the
      two muscles discharged independently of one another. In the other two conditions,
      the timing of randomly selected motor unit discharges in one muscle was adjusted
      to impose low or high levels of synchrony with motor units in the other muscle.
      Fast Fourier transform analysis was performed to compute the phase differences
      between forces from 0.5 to 17 Hz. We used circular statistics to assess whether
      the phase differences at each frequency were randomly or non-randomly distributed
      (Rayleigh test). The mean phase difference was then computed on the non-random
      distributions. We found that the number of significant phase-difference
      distributions increased markedly with increasing synchronization strength from
      18% for no synchrony to 65% and 82% for modest and strong synchrony conditions,
      respectively. Importantly, most of the mean angles clustered at very small phase
      difference values (approximately 0 to 10 degrees), indicating a strong tendency
      for forces to be exerted in a synchronous fashion. These results suggest that
      motor unit synchronization could play a significant functional role in the
      coordination of grip forces.

PMID- 15558253
TI  - Excitotoxic lesions of the pedunculopontine tegmental nucleus in rats impair
      performance on a test of sustained attention.
AB  - Recent research has suggested that the pontomesencephalic tegmentum might be an
      important part of a network underlying sustained attention. The largest structure
      of the pontomesencephalic tegmentum is the pedunculopontine tegmental nucleus,
      which has ascending connections to thalamus and with corticostriatal systems. In
      this experiment we examined the performance of rats following bilateral
      excitotoxic lesions of the pedunculopontine tegmental nucleus on a test of
      sustained attention previously used to examine frontal cortical function. After
      an initial period of darkness, the rats had to attend continuously to a dim
      stimulus light that would, at unpredictable intervals, become transiently
      brighter. During this period of increased stimulus brightness the rats could
      press a lever to obtain a food reward. Rats were trained to a criterion level of
      performance before lesions were made. After surgery, sham lesioned rats (n=7)
      resumed accurate responding, with an average successful detection rate of
      approximately 70%. Pedunculopontine lesioned rats (n=7), however, only achieved a
      successful detection rate of approximately 40%. When the duration of the bright
      target stimulus was increased from 1.5 to 4 s, the performance of the
      pedunculopontine lesioned rats significantly improved. The observation that an
      increase in brightness duration caused a marked improvement in lesioned rats'
      performance suggests strongly that the impairment was in attention rather than
      motor ability or simple sensory processing. These data are taken to be consistent
      with the hypothesis that the pedunculopontine tegmental nucleus is an important
      part of a network maintaining attention.

PMID- 15558254
TI  - Role of the cerebellum in movements: control of timing or movement transitions?
AB  - Patients with cerebellar damage are impaired on a range of timed tasks. However,
      recent research has indicated that the impairment on temporal production tasks is
      limited to discontinuous movements. The present experiments were designed to
      compare two accounts for the increased temporal variability observed in these
      patients when producing discontinuous movements. First, the impairment on
      discontinuous movements may be the result of the requirements associated with
      transitioning between movement onsets and offsets, requirements unique to
      discontinuous movement production. Second, the impairment may reflect a
      requirement to represent the temporal goal in timed, discontinuous movements.
      Patients with unilateral or bilateral cerebellar lesions and matched control
      subjects performed a key-pressing task. In one condition, the participants
      pressed and immediately released the key. The other conditions required the
      participants to press the key, and after either a 550-ms or 950-ms delay, release
      the key. Individuals with cerebellar damage were impaired on the two timed
      conditions. These results do not support the transition hypothesis. Rather, they
      are consistent with the hypothesis that the cerebellum is essential for tasks
      requiring precise event-like temporal control.

PMID- 15558256
TI  - The ALARA concept in pediatric CR and DR: dose reduction in pediatric
      radiographic exams--a white paper conference executive summary.

PMID- 15558257
TI  - Proceedings of the Second ALARA Conference. February 28, 2004. Houston, Texas,
      USA.

PMID- 15558258
TI  - Radiosensitivity of children: potential for overexposure in CR and DR and
      magnitude of doses in ordinary radiographic examinations.
AB  - The linear, no-threshold model is currently the best estimate of risk from
      radiation exposure with no level below which radiation is safe. Plain-film
      radiography has a much lower patient dose than CT or fluoroscopy. With the advent
      of computed radiography (CR) the dose to patients is higher than screen-film
      radiography and overexposure is quite common. Task-oriented adjustment of
      technique, commonly used in CT, is rarely used in CR. Exposure reduction is
      important in CR as research indicates an increased risk of childhood acute
      lymphocytic leukemia from plain-film studies and an increased risk of fatal
      breast cancer from scoliosis series. Future needs include better documentation of
      the dose the patient receives, dose-based research on the radiation risk, and
      accreditation in CR and digital radiography for public assurance.

PMID- 15558259
TI  - Assessment of the problem: pediatric doses in screen-film and digital
      radiography.
AB  - In diagnostic radiology, radiation exposure measures the amount of radiation at a
      given location in an x-ray beam, dose measures the energy deposited in a
      specified absorber, and equivalent dose quantifies the biological harm expected
      from this deposited energy. The effective dose attempts to account for the energy
      deposited in all irradiated organs as well as their relative radiosensitivity,
      and is the best available descriptor of the stochastic patient risk. Effective
      doses can be estimated from measures of the radiation beam incident on the
      patient as either entrance skin dose or dose-area product in conjunction with
      appropriate conversion coefficients. These effective dose-conversion coefficients
      are influenced by the patient size, exposed body region, x-ray beam quality, and
      x-ray beam area. We present values of skin dose, dose-area product, and effective
      dose for common examinations in pediatric patients whose size ranges from the
      newborn to adolescents. In screen-film radiography, the system speed defines the
      amount of radiation required to generate a satisfactory radiographic film
      density. Changing the screen thickness normally modifies the speed of screen-film
      systems, which affects the system resolution but not the level of image noise
      (mottle). By contrast, digital systems have a fixed resolution but can operate
      satisfactorily over a wide range of receptor dose, with the amount of noise in
      the resultant image being inversely related to the amount of radiation used. To
      ensure that patient doses are kept as low as reasonably achievable (ALARA), it is
      essential that digital receptor doses be monitored to ensure they stay constant.
      It is also important that protocols in digital radiography are specific for the
      imaging task to be performed, and use no more radiation than needed to achieve a
      satisfactory diagnosis.

PMID- 15558260
TI  - Tradeoffs between image quality and dose.
AB  - Image quality takes on different perspectives and meanings when associated with
      the concept of as low as reasonably achievable (ALARA), which is chiefly focused
      on radiation dose delivered as a result of a medical imaging procedure. ALARA is
      important because of the increased radiosensitivity of children to ionizing
      radiation and the desire to keep the radiation dose low. By the same token,
      however, image quality is also important because of the need to provide the
      necessary information in a radiograph in order to make an accurate diagnosis.
      Thus, there are tradeoffs to be considered between image quality and radiation
      dose, which is the main topic of this article. ALARA does not necessarily mean
      the lowest radiation dose, nor, when implemented, does it result in the least
      desirable radiographic images. With the recent widespread implementation of
      digital radiographic detectors and displays, a new level of flexibility and
      complexity confronts the technologist, physicist, and radiologist in optimizing
      the pediatric radiography exam. This is due to the separation of the acquisition,
      display, and archiving events that were previously combined by the screen-film
      detector, which allows for compensation for under- and overexposures, image
      processing, and on-line image manipulation. As explained in the article,
      different concepts must be introduced for a better understanding of the tradeoffs
      encountered when dealing with digital radiography and ALARA. In addition, there
      are many instances during the image acquisition/display/interpretation process in
      which image quality and associated dose can be compromised. This requires
      continuous diligence to quality control and feedback mechanisms to verify that
      the goals of image quality, dose and ALARA are achieved.

PMID- 15558261
TI  - Strategies for dose reduction in ordinary radiographic examinations using CR and
      DR.
AB  - Uncoupling of display from acquisition in computed radiography (CR) and digital
      radiography (DR) introduces the potential for systematic overexposure without
      necessarily compromising image quality. Although the magnitude of radiation doses
      in general radiography is low compared to computed tomography and fluoroscopy,
      the dose to the patient is more critical in pediatric examinations than in
      adults, because of the greater radiosensitivity of children. This manuscript
      examines a variety of countermeasures for managing radiation doses in pediatric
      CR and DR examinations, including use of derived exposure indicators,
      modifications of imaging practice, and development of more efficient radiographic
      detectors.

PMID- 15558262
TI  - Management of pediatric radiation dose using Fuji computed radiography.
AB  - This paper describes the technical details of Fuji Computed Radiography (FCR) and
      its use as it relates to managing pediatric dose for x-ray examinations. Since
      its introduction in 1983, Fuji (Fuji Photo Film Co., Ltd.) has developed an
      extensive set of menu selections with default processing algorithms and
      corresponding display processing parameters modified for all pediatric exam
      types. Continued development of imaging plate technology, FCR reader design and
      image processing have all contributed to improving image quality and creating the
      opportunity to lower the dose required for pediatric exams. Fuji continues to
      advance CR and electronic imaging technologies; some of these developments, that
      may enable lower dose examinations for pediatric imaging in the future, are also
      described in this paper.

PMID- 15558263
TI  - Management of pediatric radiation dose using Agfa computed radiography.
AB  - Radiation dose to patients and its management have become important
      considerations in modern radiographic imaging procedures, but they acquire
      particular significance in the imaging of children. Because of their longer life
      expectancy, children exposed to radiation are thought to have a significantly
      increased risk of radiation-related late sequelae compared to adults first
      exposed to radiation later in life. Therefore, current clinical thinking dictates
      that dose in pediatric radiography be minimized, while simultaneously ensuring
      sufficient diagnostic information in the image, and reducing the need for repeat
      exposures. Dose management obviously starts with characterization and control of
      the exposure technique. However, it extends farther through the imaging chain to
      the acquisition system, and even to the image processing techniques used to
      optimize acquired images for display. Further, other factors, such as quality
      control procedures and the ability to handle special pediatric procedures, like
      scoliosis exams, also come into play. The need for dose management in modern
      radiography systems has spawned a variety of different solutions, some of which
      are similar across different manufacturers, and some of which are unique. This
      paper covers the techniques used in Agfa Computed Radiography (CR) systems to
      manage dose in a pediatric environment.

PMID- 15558264
TI  - Management of pediatric radiation dose using GE's Revolution digital radiography
      systems.
AB  - Digital flat-panel x-ray detectors offer excellent image quality and dose
      efficiency in addition to clinical productivity, connectivity, and adaptability
      to advanced clinical applications. GE's Revolution systems provide two modes of
      exposure control for setting the dose operating point, fixed time and automatic
      exposure control, the latter of which maintains high image signal-to-noise ratio
      for the given technique settings. In addition to enhancing detail contrast and
      compressing the dynamic range, postprocessing automatically determines the best
      window level and width for display, taking into account the dose at which the
      image was acquired. Several studies have examined the reduction in patient dose
      achievable with Revolution systems as compared to competing technologies, and
      results indicate significant dose savings with equivalent or superior image
      quality. For pediatric exams, pediatric default techniques provide for a lower
      patient dose as compared to adult techniques. Therefore, GE's Revolution systems
      can achieve a high image quality-to-dose ratio for pediatric imaging using the
      combined advantages of dose-efficient detection, advanced postprocessing, and
      independently adjustable pediatric techniques.

PMID- 15558265
TI  - Management of pediatric radiation dose using Canon digital radiography.
AB  - A Canon CXDI-11 digital radiography (DR) system has been in use at Shands
      Hospital at the University of Florida for the past 2 1/2 years. A first clinical
      implementation phase was utilized to develop imaging protocols for adult
      patients, with a second phase incorporating pediatric chest and abdominal studies
      a few months later. This paper describes some of the steps taken during the
      modality implementation stages, as well as the methodologies and procedures
      utilized to monitor compliance by the technologists. The Canon DR system provides
      the technologist with an indication of the radiation exposure received by the
      detector (and thus of the patient dose) by means of an indirect exposure level
      number called the reached exposure (REX) value. The REX value is calculated by
      the system based on the default grayscale curve preselected for a given
      anatomical view and used by the system to optimize the appearance of the image.
      The brightness and contrast of the image can be modified by the user at the
      QC/control screen for the purpose of improving the appearance of the image. Such
      changes modify the actual grayscale curve (position and slope, respectively) and
      thus the calculated REX value. Thus, undisciplined use of the brightness and
      contrast functions by the technologist can render the REX value meaningless as an
      exposure indicator. The paper also shows how it is possible to calibrate AEC
      (phototimer) systems for use with the Canon DR system, and utilize the REX value
      as a valuable dose indicator through proper training of technologists and strict,
      disciplined QC of studies. A team consisting of the site's medical physicist,
      radiologists, and technologists, as well as Canon engineers, can work together in
      properly calibrating and setting up the system for the purposes of monitoring
      patient doses (especially pediatric) in DR studies performed in a Canon DR
      system.

PMID- 15558266
TI  - Management of pediatric radiation dose using Philips digital radiography.
AB  - Digital radiography systems based on flat-panel detectors have been introduced
      into clinical practice in the past few years. The high detective quantum
      efficiency of these detectors allows the radiation dose to be reduced while
      maintaining image quality, an issue particularly significant for pediatric
      radiography. Another important aspect for dose optimization and monitoring is the
      integration of the detector into a computer-controlled x-ray examination system.
      This enables full control and complete reporting of all dose-relevant exposure
      parameters, including the determination of the exposure indicator and the patient
      dose (kerma-area product). In this paper the implementation of these principles
      in the Philips Digital Diagnost DR system is described and their relevance for
      pediatric applications is discussed.

PMID- 15558268
TI  - Radiation doses in pediatric radiology: influence of regulations and standards.
AB  - The benefits of x-ray examinations contribute to the quality of modern medicine;
      however the risk of using x-rays, a carcinogen, has always been a concern. This
      concern is heightened for pediatric patients, who have a much greater sensitivity
      to the carcinogenic effects of radiation than adults. The principle of as low as
      reasonably achievable, or ALARA, is essential for minimizing the radiation dose
      patients receive, especially for pediatric patients. In order to keep radiation
      doses ALARA, one must know the dose patients receive. The determination of
      radiation dose in a standard way is therefore necessary so that these doses can
      be compared with practice, and for meaningful comparison against voluntary
      standards. In extreme situations, where public health needs may require mandatory
      standards, or regulations, the quantitative measurement and calculation of
      radiation dose becomes essential. How some radiation dose metrics and standards
      have evolved, including the value of different metrics such as entrance air
      kerma, organ dose, and effective dose will be presented. Recent pediatric x-ray
      studies, whether or not dedicated pediatric equipment is necessary, and recent
      initiatives by the Food and Drug Administration for pediatric population will be
      discussed.

PMID- 15558270
TI  - Myofibromatosis: imaging characteristics.
AB  - BACKGROUND: Infantile myofibromatosis is the most common fibrous tumor of
      infancy. It can involve the skin, muscle, bone, and viscera. This uncommon entity
      is subdivided into solitary and multicentric forms, with or without visceral
      involvement. OBJECTIVE: To describe the imaging characteristics of extracranial
      myofibromatosis. MATERIALS AND METHODS: Six infants, aged 1 day-1 week, were
      evaluated by imaging. All six patients had evaluation of one of the masses by US;
      four patients had CT evaluation of at least one of the masses; and five patients
      had evaluation by MRI. RESULTS: The US appearance of the myofibromas included a
      mass with a purely anechoic center with a thick wall, a mass with a partially
      anechoic center, and a mass without anechoic components. On enhanced CT, the
      masses had lower or similar attenuation compared to adjacent muscle, with some
      masses exhibiting peripheral enhancement. The MR appearance consisted of low
      signal on T1-weighted imaging. On T2-weighted imaging, two had low signal of the
      center and the other three had high signal. All masses showed peripheral
      enhancement after gadolinium administration. CONCLUSIONS: Myofibromas have
      variable appearance on US, with a mass with an anechoic center being the most
      common feature. On CT, the mass can exhibit peripheral enhancement,
      calcifications, and erosion of adjacent bone. The MR appearance consisted of low
      signal on T1-weighted imaging and high or low signal of the center on T2-weighted
      imaging. All masses showed peripheral enhancement after gadolinium
      administration.

PMID- 15558271
TI  - Sella turcica collection due to skull base osteomyelitis.

PMID- 15558272
TI  - Regulation and degradation of HMGCo-A reductase.
AB  - The enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) controls the
      biosynthesis of cholesterol. Hypercholesterolemia and atherosclerosis are
      critical health risk factors. One way of controlling these risk factors is to
      manipulate regulation as well as degradation of HMGR. At present, a class of
      compounds called statins, which are HMGR inhibitors, are used for the treatment
      of hypercholesterolemia. However, statins suffer major setbacks as their use
      produces more adverse reactions than the desirable one of inhibiting the enzyme.
      Genetically engineered forms of HMGR are also studied in primitive life forms
      like bacteria, but detailed investigation of this enzyme in human systems is
      certainly required. Extensive studies have been made on the regulatory aspects of
      this enzyme, but no breakthrough is conspicuous in the clinical background to
      find an alternative treatment for hypercholesterolemia. The immediate need is to
      find an alternate way of regulating degradation of the enzyme. This review
      presents the importance of regulation and degradation of the HMGR enzyme in
      different systems to gain possible insight into alternative schemes for
      regulating this enzyme and, if these exist, the feasibility of extending them
      same to studies in mammalian systems. A high degree of similarity exists between
      mammalian and yeast HMGR. Detailed studies reported on the regulation and
      degradation of the yeast enzyme also throw more light on the mammalian system,
      leading to a better understanding of ways of controlling hypercholesterolemia.

PMID- 15558273
TI  - Production of L-lactic acid from a mixture of xylose and glucose by co
      cultivation of lactic acid bacteria.
AB  - The production of optically pure lactic acid in a high yield from xylose or a
      mixture of xylose and glucose, which is a model hydrolysate of lignocellulose, is
      described. In a single cultivation, Enterococcus casseliflavus produced 38 g/l of
      lactic acid with an optical purity of 96% enantiomeric excess (ee) and 6.4 g/l of
      acetic acid from 50 g/l of xylose when MRS medium was used. When a mixture of 50
      g/l of xylose and 100 g/l of glucose was used as the carbon source in a
      cultivation of E. casseliflavus alone, glucose was converted to lactic acid in
      the early phase of the cultivation but xylose was hardly consumed. In a co
      cultivation where E. casseliflavus and Lactobacillus casei specific for glucose
      were simultaneously inoculated, little or no lactic acid was produced after the
      glucose was almost consumed. A co-cultivation with two-stage inoculation (in
      which E. casseliflavus was added at a cultivation time of 40 h after L. casei
      cells were inoculated) resulted in complete consumption of 50 g/l of xylose and
      100 g/l of glucose. In the co-cultivation, 95 g/l of lactic acid with a high
      optical purity of 96% ee was obtained at 192 h. Such a co-cultivation using two
      microorganisms specific for each sugar is considered to be one promising
      cultivation technique for the efficient production of lactic acid from a sugar
      mixture derived from lignocellulose.

PMID- 15558274
TI  - H2-producing bacterial communities from a heat-treated soil inoculum.
AB  - Hydrogen gas (approximately 60% H(2)) was produced in a continuous flow
      bioreactor inoculated with heat-treated soil, and fed synthetic wastewater
      containing glucose (9.5 g l(-1)). The pH in the bioreactor was maintained at 5.5
      to inhibit consumption of H(2) by methanogens. The objective of this study was to
      characterize bacterial communities in the reactor operated under two different
      hydraulic retention times (HRTs of 30-h and 10-h) and temperatures (30 degrees C
      and 37 degrees C). At 30-h HRT, the H(2) production rate was 80 ml h(-1) and
      yield was 0.91 mol H(2)/mol glucose. At 10-h HRT, the H(2) production rate was
      more than 5 times higher at 436 ml h(-1), and yield was 1.61 mol H(2)/mol
      glucose. Samples were removed from the reactor under steady-state conditions for
      PCR-based detection of bacterial populations by ribosomal intergenic spacer
      analysis (RISA). Populations detected at 30-h HRT were more diverse than at 10-h
      HRT and included representatives of Bacillaceae, Clostridiaceae, and
      Enterobacteriaceae. At 10-h HRT, only Clostridiaceae were detected. When the
      temperature of the 10-h HRT reactor was increased from 30 degrees C to 37 degrees
      C, the steady-state H(2) production rate increased slightly to 463 ml h(-1) and
      yield was 1.8 mol H(2)/mol glucose. Compared to 30 degrees C, RISA fingerprints
      at 37 degrees C from the 10-h HRT bioreactor exhibited a clear shift from
      populations related to Clostridium acidisoli (subcluster Ic) to populations
      related to Clostridium acetobutylicum (subcluster Ib).

PMID- 15558275
TI  - Effect of NADH dehydrogenase-disruption and over-expression on respiration
      related metabolism in Corynebacterium glutamicum KY9714.
AB  - The function of type II NADH dehydrogenase (NDH-2) in Gram-positive
      Corynebacterium glutamicum was investigated by preparing strains with ndh, the
      NDH-2 gene, disrupted and over-expressed. Although disruption showed no growth
      defects on glucose minimum medium, the growth rate of the over-expressed strain
      was lower compared with its parent, C. glutamicum KY9714. Ndh-disruption and over
      expression did not lead to a large change in the respiratory chain and
      energetics, including the cytochrome components and the H(+)/O ratio. However, in
      the strain that lacked NDH-2, membrane L-lactate oxidase activity increased,
      while NDH-2 over-expression led to decreased L-lactate and malate oxidase
      activities. In addition, relatively high cytoplasmic lactate dehydrogenase (LDH)
      activity was always present as was malate dehydrogenase, irrespective of NDH-2
      level. Furthermore, L-lactate or malate-dependent NADH oxidase activity could be
      reproduced by reconstitution with the membranes and the cytoplasmic fraction
      isolated from the disruptant. These results suggest that coupling of LDH and the
      membrane L-lactate oxidase system, together with the malate-dependent NADH
      oxidase system, operates to oxidize NADH when the NDH-2 function is defective in
      C. glutamicum.

PMID- 15558276
TI  - beta-Glucan synthase induction in mushrooms grown on olive mill wastewaters.
AB  - beta-1-3-Glucan synthase activity and its induction by olive mill wastewaters
      (OMW) was studied in ten fungal strains (Auricularia auricula-judae, Lentinula
      edodes, Pleurotus eryngii, Stropharia aeruginosa, Agrocybe aegerita, P.
      pulmonarius, Armillaria mellea, P. ferulae, P. ostreatus, P. nebrodensis). A
      microtiter-based enzymatic assay on beta-1-3-glucan synthase activity was carried
      out on all mycelia growth both on the control medium and on OMW. Among the fungi
      assayed, L. edodes beta-1-3-glucan synthase was highly enhanced in OMW. The main
      components of OMW, i.e. phenols and lipids, were added separately to the control
      medium, to highlight the mechanism of L. edodes beta-1-3-glucan synthase
      induction. A Southern blot analysis and PCR with degenerated primers were carried
      out to detect the presence of fks1-like genes in these Basidiomycetes. The
      sequences obtained from the ten Basidiomycota were remarkably similar to fks1
      from Filobasidiella neoformans. Spectrofluorimetric and RT-PCR analyses of beta-1
      3-glucan synthase were performed on the mycelia of L. edodes. In this fungus, a
      strong stimulation of beta-1-3-glucan synthase mRNA and protein was recorded in
      the presence of OMW and phenols.

PMID- 15558277
TI  - Treatment of dairy effluents in an aerobic granular sludge sequencing batch
      reactor.
AB  - Aerobic granular sludge can successfully be cultivated in a sequencing batch
      reactor (SBR) treating dairy wastewater. Attention has to be paid to the fact
      that suspended solids are always present in the effluent of aerobic granular
      sludge reactors, making a post-treatment step necessary. Sufficient post
      treatment can be achieved through a sedimentation process with a hydraulic
      retention time of 15-30 min. After complete granulation and the separation of
      biomass from the effluent, removal efficiencies of 90% CODtotal, 80% Ntotal and
      67% Ptotal can be achieved at a volumetric exchange ratio of 50% and a cycle
      duration of 8 h. Effluent values stabilize at around 125 mg l-1 CODdissolved. The
      maximum applicable loading rate is nevertheless limited, as the stability of
      aerobic granules very much depends on the presence of distinct feast and famine
      conditions and the degradation of real wastewaters shows slower kinetics compared
      with synthetic wastewaters. As loading rate and volumetric exchange ratio are
      coupled in an SBR system, the potential of granular sludge for improving process
      efficiency is also limited.

PMID- 15558278
TI  - Entrapment of the acetabular labrum following reduction of traumatic hip
      dislocation in a child.
AB  - In traumatic hip dislocation, concentric reduction can be prevented by various
      causes. Soft-tissue interposition, such as entrapment of the acetabular labrum,
      is a rare but important cause of failed reduction of a hip. Early diagnosis of
      incomplete reduction due to interposition of soft tissue is important, because
      delayed treatment is associated with a greater incidence of avascular necrosis of
      the femoral head and early onset of osteoarthritis. This report describes a case
      of acetabular labral entrapment following reduction of traumatic hip dislocation
      in a child. The importance of CT and MRI in arriving at an early diagnosis is
      emphasized.

PMID- 15558281
TI  - Immunoprevention and immunotherapy of cancer in ageing.
AB  - Over the last few years there has been a growing interest in geriatric oncology,
      mainly because of the evidence that advanced age is the greatest risk factor for
      the development of cancer and that, since the elderly population is rapidly
      expanding, so too will the number of cancer patients. This forecast necessitates
      the development of new and more specific strategies for the prevention and cure
      of cancer in the elderly and as a result an ever-increasing need for oncologists,
      geriatricians and researchers to work closely together. The increased incidence
      of cancer in elderly people has been related to the age-associated changes
      occurring in the immune system, the so-called immunosenescence. This phenomenon
      is best characterised by a remodelling of the immune system, which appears early
      on and progresses throughout a person's life and mainly involves a decrease in
      cellular functions. This review aims to provide a rationale for the development
      of specific immunotherapeutic and immunopreventive regimens for the elderly. We
      also include a discussion on the influence that immunosenescence has on the
      growth of tumours and the effectiveness of immunogene therapy and cancer
      vaccination following a brief analysis of the age-related alterations of the cell
      populations involved in antitumour immunity.

PMID- 15558282
TI  - Intraocular lymphoma as a masquerade syndrome complicating cerebral lymphoma of
      the corpus callosum.

PMID- 15558283
TI  - The place of cladribine in the treatment of chronic lymphocytic leukemia: a 10
      year experience in Poland.
AB  - Cladribine (2-CdA) is structurally similar to another purine analog, fludarabine
      (FA), recently accepted in several centers as the first-line treatment in chronic
      lymphocytic leukemia (CLL). Unfortunately, there is less experience with the use
      of 2-CdA than with FA in patients with CLL in the majority of Western countries.
      In the last decade we performed several phase II studies and two phase III
      randomized trials to evaluate the activity and toxicity of 2-CdA in previously
      treated and untreated patients with CLL. We have also compared the results of
      Polish studies with the data presented by other investigators. Similarly to FA
      this agent has been found to be more effective in previously untreated CLL than
      in patients refractory to or relapsed after conventional therapy with alkylating
      agents. In different studies the overall response (OR) rate ranged from 70 to 85%
      and complete response (CR) from 10 to 47%. Higher CR and OR rates in CLL patients
      treated with 2-CdA and prednisone than with chlorambucil and prednisone were
      confirmed in our multicenter, randomized study. Subsequently, we performed a
      multicenter, randomized study comparing 2-CdA alone with a combination of 2-CdA
      and cyclophosphamide (CC) or cyclophosphamide and mitoxantrone (CMC). Our updated
      results seem to indicate that the CC program used as a first-line therapy in CLL
      gives higher CR and OR and better elimination of minimal residual disease (MRD)
      than 2-CdA alone. CC is also less myelotoxic than CMC. More recently, we have
      undertaken a phase II study to determine the efficacy and toxicity of 2-CdA
      combined with the anti-CD20 monoclonal antibody rituximab in CLL and other
      refractory or relapsed indolent lymphoproliferative disorders. The preliminary
      results seem to be better than in similar patients previously treated in our
      institution with 2-CdA alone. In conclusion, the studies performed in the last
      decade in Poland and other countries have shown that 2-CdA used alone or in
      combination with other agents is, similarly to FA, a highly active and relatively
      safe agent in previously treated and untreated patients with CLL.

PMID- 15558284
TI  - Differential regulation of Tec1 by Fus3 and Kss1 confers signaling specificity in
      yeast development.
AB  - Transcriptional regulation by mitogen-activated protein (MAP) kinase signaling
      cascades is a major control mechanism for eukaryotic development. In budding
      yeast, Fus3 and Kss1 are two MAP kinases that control two distinct developmental
      programs-mating and invasive growth. We investigated whether signal-specific
      activation of mating and invasive growth involves regulation of the transcription
      factor Tec1 by Fus3 and Kss1. We present evidence that, during mating, Fus3
      phosphorylates Tec1 to downregulate this invasive growth-specific transcription
      factor and its target genes. This function of Fus3 is essential for correct
      execution of the mating program and is not shared by Kss1. We find that Kss1
      controls the activity of Tec1 mainly during invasive growth by control of TEC1
      gene expression. Our study suggests that signaling specificity can arise from
      differential regulation of a single transcription factor by two MAP kinases with
      shared functions in distinct developmental programs.

PMID- 15558285
TI  - From axenic spore germination to molecular farming. One century of bryophyte in
      vitro culture.
AB  - The first bryophyte tissue culture techniques were established almost a century
      ago. All of the techniques that have been developed for tissue culture of seed
      plants have also been adapted for bryophytes, and these range from mere axenic
      culture to molecular farming. However, specific characteristics of bryophyte
      biology--for example, a unique regeneration capacity--have also resulted in the
      development of methodologies and techniques different than those used for seed
      plants. In this review we provide an overview of the application of in vitro
      techniques to bryophytes, emphasising the differences as well as the similarities
      between bryophytes and seed plants. These are discussed within the framework of
      physiological and developmental processes as well as with respect to potential
      applications in plant biotechnology.

PMID- 15558286
TI  - Initial and long-term management of posterior urethral valves.
AB  - Posterior urethral valves are the most common cause of congenital obstructive
      uropathy, resulting in renal failure in childhood. Nowadays, in most cases,
      diagnosis is suggested by antenatal ultrasound. However, antenatal intervention
      has not resulted in a significantly improved outcome. Endoscopic valve ablation
      is the initial treatment in most of these neonates, but others procedures, like
      vesicostomy or ureterostomy, can also be justified in some particular cases in
      order to improve renal function prognosis. Different factors like bladder
      dysfunction, VUR, polyuria and proteinuria, can be responsible for the slow and
      progressive deterioration in renal function that some of these patients show over
      the years. By treating them all, we may prevent or delay the onset of end stage
      renal disease.

PMID- 15558287
TI  - Gliding behaviour elicited by lateral looming stimuli in flying locusts.
AB  - We challenged tethered, flying locusts with visual stimuli looming from the side
      towards one eye in a way that mimics the approach of a predatory bird. Locusts
      respond to the lateral approach of a looming object with steering movements and a
      stereotyped, rapid behaviour in which the wingbeat pattern ceases and the wings
      are swept into a gliding posture. This gliding behaviour may cause the locust to
      dive. The gliding posture is maintained for 200 ms or more after which flight is
      resumed with an increased wingbeat frequency or else the wings are folded. A
      glide begins with a strong burst of activity in the mesothoracic second
      tergosternal motor neuron (no. 84) on both sides of the locust. Recordings of
      descending contralateral movement detector (DCMD) activity in a flying locust
      show that it responds to small (80-mm diameter) looming stimuli during tethered
      flight, with a prolonged burst of spikes that tracks stimulus approach and
      reaches peak instantaneous frequencies as, or after, stimulus motion ceases.
      There is a close match between the visual stimuli that elicit a gliding behaviour
      and those that are effective at exciting the DCMD neuron. Wing elevation into the
      gliding posture occurs during a maintained burst of high frequency DCMD spikes.

PMID- 15558288
TI  - Light dependence of oxygen consumption by blowfly eyes recorded with a magnetic
      diver balance.
AB  - We measured the oxygen (O2) consumption of isolated blowfly eyes using a magnetic
      diver balance, a device for high-resolution volumetric O2 consumption
      measurements. The light-induced O2 consumption is at most three times the value
      of the dark consumption, which is 0.6 nl O2 s(-1) eye(-1), and is in good
      agreement with the estimates based on electrophysiological data. With longer
      stimuli the increase follows a double exponential time course. The respective
      time constants are approximately 2 and 20 s and show no dependence on light
      intensity, whereas the dependence of amplitudes can be fitted by a Hill equation.
      Decreasing the stimulus duration reveals that the peak in O2 consumption
      overshoots the time course induced by long stimuli. We suggest this may be a
      general feature of mitochondrial activation. The dependence of the O2 consumption
      peak on stimulus duration at high light intensity has a hump with stimulus
      durations of 10-20 ms, coinciding with the stimulus durations that start to
      induce the adaptation of the receptor potential.

PMID- 15558289
TI  - The circadian Clock mutant mouse: impaired masking response to light.
AB  - Synchronization of an internal clock (entrainment) and a direct response to light
      (masking) are complementary ways of restricting activity of an animal to day or
      night. The protein CLOCK has an important role in the oscillatory mechanism of
      mammalian pacemakers. Our data show that it is also involved in masking
      responses. Mice with the Clock/Clock mutation reduced their wheel running less
      than wildtypes when given 1-h light pulses of light (2-1,600 lx) in the night.
      With dimmer lights (<2 lx), there were no significant differences between mutant
      and wildtype mice. Impaired masking responses to light in Clock/Clock mice were
      confirmed in tests with ultradian light-dark cycles (3.5:3.5 h and 1:1 h). Tests
      with pulses of light longer than 1 h revealed that, although the mutants
      responded more slowly to light, they sustained the suppression of activity over
      the course of the 3-h tests better than wildtypes.

PMID- 15558290
TI  - Colitis cystica profunda and giant inflammatory pseudopolyp in Crohn's disease.

PMID- 15558291
TI  - Loss of glycosylation associated with the T183A mutation in human prion disease.
AB  - A heterozygous T183A mutation in the prion protein (PrP) gene, PRNP, was
      identified in a patient with histopathologically confirmed spongiform
      encephalopathy. Clinically, this form of prion disease was characterized by early
      onset dementia as the predominant sign, along with global cerebral atrophy and
      hypometabolism. The age at onset was 40 years and the disease duration was 4
      years. Additional neurological signs including cerebellar ataxia and EEG
      abnormalities were absent until late stages of the disease. The T183A mutation
      was not found in non-affected family members. This mutation results in the
      removal of one of the two consensus sites for glycosylation of PrP.
      Neuropathological examination revealed severe spongiform degeneration and
      neuronal loss in the neocortex, putamen and claustrum, small plaque-like PrP
      immunoreactive deposits in the molecular layer of the cerebellum, and faint
      intracellular cytoplasmic PrP immunoreactivity. Western blot analysis of the
      patient's brain tissue showed protease K-resistant PrP with a definite
      preponderance of the monoglycosylated form. The additional appearance of a band
      representing diglycosylated PrPSc strongly suggests that non-mutated PrP also
      acquires protease resistance in the present setting. Cell culture experiments
      confirmed previous reports on intracellular retention of the mutant protein in
      vitro. This is the second report of a disease-causing T183A mutation of PrP, and
      the clinical, histological and genetic observations strongly suggest that T183A
      is a disease-causing mutation.

PMID- 15558292
TI  - Clear cell chondrosarcoma of the proximal femur with intrapelvic extension.
AB  - Clear cell chondrosarcoma is a rare tumor that can be easily confused with benign
      tumors. The aim of this report is to present a case that is rare, initially
      diagnosed as aneurysmal bone cyst and then chondroblastoma, and has an
      interesting extension pattern. A 41-year-old male patient was treated for an
      apparently benign cystic lesion of the right proximal femur by intralesional
      excision and bone grafting. The pathological diagnosis was aneurysmal bone cyst.
      Two years later, the patient presented with a pathological fracture at the same
      site and a total hip arthroplasty was performed. The pathological specimen was
      diagnosed as chondroblastoma. Three years later, clinical and radiological
      examination of the patient revealed a large mass located on the intrapelvic side
      of the acetabulum. There was no evidence of distant metastases. Both tumors were
      resected with a wide margin on the femoral side and a marginal margin on the
      intrapelvic side. The extremity was reconstructed with a resection-type total hip
      prosthesis. Again, the pathological diagnosis was chondroblastoma. The patient
      developed a deep infection that was treated by antibiotic therapy and surgical
      debridement. One year later, there was recurrence of the femoral and intrapelvic
      masses and right hemipelvectomy was performed; the specimen was reported as clear
      cell chondrosarcoma. Since then, the patient has been leading an active life, and
      there is no evidence of local recurrence or distant metastasis. Clinically and
      pathologically, clear cell chondrosarcoma may be confused with benign bone
      tumors. This caused a delay in the final diagnosis of this patient and he
      received inadequate surgical treatment, leading to a hemipelvectomy. We also
      found that the intrapelvic mass seemed to have developed independently on the
      intrapelvic side of the acetabulum. We were unable to find an exact explanation
      for this finding and postulated that tumor cells might have been seeded into the
      inner wall of the acetabulum during acetabular preparation of the total hip
      prosthesis.

PMID- 15558293
TI  - Biomechanical properties of heat-treated bone grafts.
AB  - INTRODUCTION: A possible critical complication associated with banking bone is
      human immunodeficiency virus (HIV) infection. Recently, since the report of HIV
      infection in bone allografts from an HIV-seronegative donor, a more reliable
      method of sterilization for preserved bone graft has become necessary. Heat
      treatment of banking bone is one of the simple sterilization methods. This method
      is especially safe and practical for the prevention of HIV infection. MATERIALS
      AND METHODS: We previously reported a biological study on heat-treated bone
      graft. In that study, we showed that revascularization and new bone formation of
      bone graft after heat treatment at 60 degrees C was nearly the same as that of
      non-heat-treated bone graft, while at 100 degrees C, revascularization and new
      bone formation showed a significant delay. This time, we examined the change of
      mechanical strength of heat-treated bone grafts after transplantation in an
      experiment. To eliminate the problem of antigenicity of grafted bone, we used
      autografts, not allografts. Two types of heat-treated autografts were employed:
      heat-treated at 60 degrees C for 30 min and heat-treated at 100 degrees C for 5
      min; as a control, fresh autografts were replaced in the left femur of rabbits. A
      strength test was performed for both the transplanted bone and the untreated
      intact right femur with time after transplantation. The strength test consisted
      of a compression test and torsional test, and the strength was compared between
      transplanted bone and the untreated intact right femur. RESULTS: In the
      compression test, the grafts heat-treated at 60 degrees C showed a strength ratio
      before transplantation of 97.3%. The strength ratio decreased to 63.5% at 18
      weeks after transplantation. Then the strength ratio increased and recovered to
      94.5% at 48 weeks after transplantation. However, the grafts heat-treated at 100
      degrees C showed unsatisfactory mechanical strength, at 48 weeks the strength
      ratio was 60.1%, which was significantly lower compared with controls. In the
      torsional test, the grafts heat-treated at 60 degrees C showed almost the same
      strength observed in the compression test. However, the grafts heat-treated at
      100 degrees C showed unsatisfactory mechanical strength: at 48 weeks, the
      strength ratio was 57.3%. CONCLUSION: Therefore, heat treatment at 60 degrees C
      is a useful sterilization method, not only in biological but also mechanical
      terms.

PMID- 15558294
TI  - Effect of bicarbonate on retinal vasculature and acidosis-induced retinopathy in
      the neonatal rat.
AB  - BACKGROUND: Systemic acidosis induces preretinal neovascularization (NV)
      analogous to retinopathy of prematurity (ROP) in the neonatal rat. Sodium
      bicarbonate is used in human neonates to treat acidosis. The effects of alkali
      administration on the developing retinal vasculature and on acidosis-induced
      retinopathy (AIR) are unknown. We investigated the effect of sodium bicarbonate
      gavage on the retinal vasculature of normal and acidotic neonatal rats to
      determine (1) whether bicarbonate treatment is associated with preretinal NV and
      (2) whether AIR can be prevented with systemic bicarbonate treatment. METHODS:
      The extent of acidosis and alkalosis were initially determined from carotid
      arterial blood samples. In the bicarbonate-alone study, newborn rats were
      randomized into litters of 25 and received bicarbonate doses of 15 mmol/kg twice
      daily and 20 mmol/kg once daily from days 2 to 7. Control animals received saline
      gavage. In the AIR treatment study, acidosis was induced in neonatal rats by
      intraperitoneal injection of acetazolamide 200 mg/kg from days 2 to 7.
      Acetazolamide-treated rats received either additional bicarbonate gavage or no
      additional treatment. Eyes were enucleated on day 13, and the retinal vasculature
      was assessed for NV using ADPase staining techniques and light microscopy.
      RESULTS: Systemic alkalosis (peak pH 7.55+/-0.02; mean +/- SD) was confirmed with
      bicarbonate gavage, and partial reversal of acidosis was confirmed when
      acetazolamide-treated rats received bicarbonate. Surviving rats receiving
      bicarbonate 15 mmol/kg twice daily (28% survival) and 20 mmol/kg bicarbonate once
      daily (45% survival) had an incidence of preretinal NV of 9% and 8%,
      respectively. No NV was seen in saline-control rats. In the acetazolamide-treated
      rats, the incidence of preretinal NV in surviving rats was numerically lower in
      bicarbonate-treated rats than acetazolamide-only controls (8% versus 24%,
      p=0.065) but with only 19% survival in the bicarbonate-treated rats. CONCLUSIONS:
      In the neonatal rat, alkalosis induced by bicarbonate gavage is associated with a
      low incidence of mild, preretinal NV similar to ROP. Although treating acidotic
      rats with bicarbonate may reduce the incidence of preretinal NV, treatment was
      associated with an unacceptable mortality rate.

PMID- 15558295
TI  - The clinicopathological spectrum of benign peripunctal tumours.
AB  - PURPOSE: Because of the rarity of peripunctal tumours and their clinical
      classification as conjunctival or eyelid tumours, they have gained little
      attention in the literature. We conducted a retrospective study to illustrate the
      different clinical and histopathological spectrum of peripunctal tumours seen at
      two oculoplastics clinics. METHODS: In a retrospective interventional
      clinicopathologic case series study, all the charts of patients with peripunctal
      tumours presented at an ophthalmic oncology clinic in Jerusalem, Israel and an
      oculoplastics clinic in Boston, USA were reviewed. The tumours were classified as
      epithelial and non-epithelial tumours. The symptoms caused by these tumours,
      their pattern of growth and their management were evaluated. RESULTS: Fourteen
      peripunctal tumours were identified. Eleven out of 175 (6.3%) peripunctal
      disorders and out of approximately 4,000 (0.27%) surgical oculoplastics patients
      were seen at Massachusetts Eye & Ear Infirmary, Boston. Three were seen at
      Hadassah University Hospital, Jerusalem. Seven histopathological types of
      peripunctal tumours of epithelial, subepithelial or melanocytic origin causing
      punctal occlusion or displacement were identified. The tumours included compound
      and junctional naevi, non-pigmented compound naevus, epithelial, subepithelial
      inclusion cysts, verrucous and squamous papilloma, pyogenic granuloma and
      oncocytoma. All the tumours were benign. They involved the peripunctal or
      canalicular epithelium, the adjacent skin, the glandular epithelium or the
      subepithelium. They presented as a peripunctal mass or were accidentally
      disclosed but none of them resulted in epiphora. CONCLUSIONS: Peripunctal tumours
      are rare. They exhibit different clinical types of growth and may be difficult to
      diagnose based on their clinical appearance alone. The location of peripunctal
      tumours potentially allows their extension from the conjunctival sac into the
      canaliculus and vice versa. Therefore, it is best to ascertain free margins when
      the tumour is excised.

PMID- 15558296
TI  - Shear stress-induced upregulation of connexin 43 expression in endothelial cells
      on upstream surfaces of rat cardiac valves.
AB  - Endothelial expression of the gap junction proteins, connexin (Cx) 37, Cx40, and
      Cx43, varies within the vascular network. While previous studies suggest that
      shear stress may upregulate Cx43, it is not well understood if shear stress
      affects the expression of all endothelial connexins and to what extent.
      Endothelial cells on the upstream and downstream surfaces of cardiac valves are
      subjected to considerably different intensities of shear stress. We therefore
      reasoned that we could determine the extent hemodynamic forces affect the
      expression of Cx37, Cx40, and Cx43 by comparing their immunohistochemical
      distribution on the upstream and downstream surfaces of rat cardiac valves. We
      found 70- to 200-fold greater expression of Cx43 in the endothelial cells on the
      upstream than on the downstream surfaces. However, Cx37 was expressed almost
      equally in the endothelial cells on upstream and downstream surfaces, and Cx40, a
      major connexin in most vascular endothelial cells, was not detected on either
      surface. In addition to the heterogeneity in Cx43 expression, endothelial cells
      on the upstream surface were 35% to 65% smaller than those on the corresponding
      downstream surface. These results suggest that shear stress may affect
      endothelial cell size and Cx43 expression but not Cx37 expression.

PMID- 15558297
TI  - Association of connexin36 with zonula occludens-1 in HeLa cells, betaTC-3 cells,
      pancreas, and adrenal gland.
AB  - The PDZ domain-containing protein zonula occludens-1 (ZO-1), a well-established
      component of tight junctions, has recently been shown to interact with various
      connexin proteins that form gap junctions. We investigated the association of
      connexin36 (Cx36) with ZO-1 in various cultured cells and tissues. Punctate
      immunofluorescence labeling for Cx36 was detected in Cx36-transfected HeLa cells,
      betaTC-3 cells, pancreatic islets, and adrenal medulla. Immunofluorescence for ZO
      1 was also punctate in cells and tissues, and was colocalized with Cx36 at points
      of cell-cell contact. Immunoprecipitation of either Cx36 or ZO-1 from cell
      lysates and tissue homogenates resulted in immunoblot detection of ZO-1 or Cx36,
      respectively, in immunoprecipitates. A 14-amino acid peptide corresponding to the
      carboxy-terminus of Cx36 showed binding capacity to the PDZ1 domain of ZO-1,
      which was eliminated after removal of the last 4 carboxy-terminus amino acids.
      Low micromolar concentrations of the 14-amino acid peptide produced up to 85%
      inhibition of Cx36 interaction with the PDZ1 domain of ZO-1. These results
      provide evidence for molecular interaction between Cx36 and ZO-1 in vitro, and in
      vivo, and suggest that the interference with Cx36/ZO-1 interaction by short
      carboxy-terminus peptides of Cx36 may be of value for functional studies of this
      interaction.

PMID- 15558298
TI  - Symptoms in relation to chemicals and dampness in newly built dwellings.
AB  - OBJECTIVES: As the airtightness of dwellings has recently increased, problems
      associated with indoor air pollution and dampness have become important
      environmental health issues. The aim of this study was to clarify whether
      symptoms in residents living in newly built dwellings were related to chemicals
      and dampness. METHODS: Symptoms of 317 residents were surveyed by standardized
      questionnaires, and the concentrations of formaldehyde, acetaldehyde, and 17
      volatile organic compounds (VOCs) in their homes were measured. Dampness
      (condensation on window panes and/or walls, and mold growth) was identified by
      questionnaires given to the householders or their partners. RESULTS: Some VOCs
      (toluene, butyl acetate, ethylbenzene, alpha-pinene, p-dichlorobenzene, nonanal,
      and xylene) were significantly related to the symptoms, and the sum of all VOCs
      (all identified VOCs) was significantly related to throat and respiratory
      symptoms [odds ratio (OR) for eye symptoms =2.4; 95% confidence interval (CI) 1.0
      5.5], although the concentrations of VOCs were relatively low. As for the
      dampness index, condensation on window panes and/or walls was related to all
      symptoms, and mold growth was related to all symptoms except skin, throat and
      respiratory and general symptoms. As the number of dampness signs increased, the
      ORs increased for the symptoms except general symptoms (OR for nose symptoms =
      4.4, 95% CI 1.6-11.9). CONCLUSION: Both VOCs and dampness were significantly
      related to symptoms. We should take measures to reduce the concentrations of
      VOCs, dampness and microbial growth in dwellings.

PMID- 15558299
TI  - Radiographic outcomes among South African coal miners.
AB  - OBJECTIVES: This study, the first to document the prevalence of pneumoconiosis
      among a living South African coal mining cohort, describes dose-response
      relationships between coal workers' pneumoconiosis and respirable dust exposure,
      and relationships between pneumoconiosis and both lung function deterioration and
      respiratory symptoms. METHODS: A total of 684 current miners and 188 ex-miners
      from three bituminous-coal mines in Mpumalanga, South Africa, was studied. Chest
      radiographs were read according to the International Labour Organization (ILO)
      classification by two experienced readers, one an accredited National Institute
      for Occupational Safety and Health (NIOSH) "B" reader. Interviews were conducted
      to assess symptoms, work histories (also obtained from company records), smoking,
      and other risk factors. Spirometry was performed by trained technicians.
      Cumulative respirable dust exposure (CDE) estimates were constructed from
      historical company-collected sampling and researcher-collected personal dust
      measurements. kappa-Statistics compared the radiographic outcomes predicted by
      the two readers. An average profusion score was used in the analysis for the
      outcomes of interest. Because of possible confounding by employment status, most
      analyses were stratified on current and ex-miner status. RESULTS: The overall
      prevalence of pneumoconiosis was low (2%-4%). The degree of agreement between the
      two readers for profusion was moderate to high (kappa=0.58). A significant
      association (P<0.001) and trend (P<0.001) was seen for pneumoconiosis with
      increasing categories of CDE among current miners only. A significant (P<0.0001)
      additional 58 mg-years/m3 CDE was seen among those with pneumoconiosis compared
      to those without. CDE contributed to a statistically significant 0.19% and 0.11%
      greater decline in the percent predicted 1-second forced expiration volume (FEV1)
      and forced vital capacity (FVC), respectively, among current miners with
      pneumoconiosis than among those without. Logistic regression models showed no
      significant relationships between pneumoconiosis and symptoms. CONCLUSIONS: The
      overall prevalence of pneumoconiosis, although significantly associated with CDE,
      was low. The presence of pneumoconiosis is associated with meaningful health
      effects, including deterioration in lung function. Intervention measures that
      control exposure are indicated, to reduce these functional effects.

PMID- 15558300
TI  - Functional, postural and perceived balance for predicting the work ability of
      firefighters.
AB  - OBJECTIVE: The importance of balance abilities for firefighting and rescue work
      has already been recognized, but there are no valid balance tests available in
      the test batteries for the physical work capacity of firefighters. Moreover, few
      studies have examined the associations between balance and work ability in
      general. Valid work-related balance tests are needed for the purpose of screening
      in occupational health care and in rehabilitation for assessing the effects of
      balance training. This study aimed to investigate the predictive value of
      functional, postural and perceived balance in respect to work ability among
      firefighters at baseline and after a 3-year follow-up. METHODS: The subjects were
      135 male firefighters aged 33-56 years. The outcome variables were the work
      ability index and perceived physical work ability (PWA), determined by
      questionnaire in 1996 and 1999. The predictors assessed in 1996 were postural
      balance (tested with a force platform), functional balance (measured during
      walking on a wooden plank), and perceived balance abilities, enquired about
      through a questionnaire. RESULTS: Most of the balance test results and the
      perceived balance ability were associated with the perceived PWA at baseline. The
      final logistic regression models showed that the best predictors of decreased
      work ability among firefighters after 3 years were poor-to-moderate perceived
      balance [odds ratios (ORs) 2.4, 95% confidence interval (CI) 0.9-6.6]; more than
      one error in the functional balance test (OR 3.6, 95% CI 1.0-12.7); and a high
      mean amplitude of postural sway with the eyes closed (OR 2.7, 95% CI 0.9-6.1).
      CONCLUSIONS: The results support the work-related and predictive validity, in
      terms of perceived work ability, perceived balance, errors in the functional
      balance test and amplitude of postural sway with the eyes closed, of measuring
      balance among firefighters.

PMID- 15558301
TI  - Deaths from nasopharyngeal cancer among waiters and waitresses in Chinese
      restaurants.
AB  - OBJECTIVE: Previous studies have shown that waiters have a high risk of
      developing cancers of the buccal cavity and pharynx, but nasopharyngeal cancer
      (NPC) has not been specifically studied. This study was carried out to
      investigate whether waiters/waitresses in Chinese restaurants have an increased
      risk of dying from NPC. METHODS: A mortality odds ratio study was used to
      estimate the relative risk of dying from NPC for waiters/waitresses working in
      Chinese restaurants in Hong Kong during the period 1986-1995, using the general
      population as the external comparison group and deceased kitchen workers as an
      internal comparison group. Cases were deaths from NPC and the controls were
      deaths from the selected sets of reference causes. RESULTS: Seventeen deaths from
      NPC were identified among 415 deceased waiters and four NPC deaths occurred among
      140 deceased waitresses. The adjusted mortality odds ratio (aMOR) for NPC was
      increased among waiters, being 3.02 (95% CI 1.82-5.00) and 2.61 (95% CI 1.02
      6.69) in the external and internal comparisons, respectively. For waitresses, the
      aMOR was 4.58 (95% CI 1.63-12.86) in the external comparison. Analysis by
      duration of union membership suggested a dose-response relationship. CONCLUSIONS:
      An increased risk of dying from NPC was observed among waiters/waitresses and
      could not be fully explained by bias or confounding factors. Possible risk
      factors related to poor indoor air quality in the service areas of Chinese
      restaurants in Hong Kong should be further investigated.

PMID- 15558302
TI  - Feedback of workplace data to individual workers, workgroups or supervisors as a
      way to stimulate working environment activity: a cluster randomized controlled
      study.
AB  - OBJECTIVE: To test whether feedback and discussion of ergonomic and psychosocial
      working-environment data during one short session with individual, groups or
      supervisors of white-collar computer workers had an effect on activity to modify
      workplace design, working technique and psychosocial aspects of work. METHODS: A
      total of 36 workgroups from nine organizations representing different trades was
      randomized (stratified for organization) to three feedback conditions or control
      with no feedback. Data were collected 1 month before and 6 months after feedback
      sessions. The effects studied were: (1) change in the proportion of workgroup
      members who reported any modification regarding workplace design or working
      technique; (2) change in the proportion of workgroup members who reported any
      modification regarding psychosocial aspects; (3) average number of modification
      types regarding workplace design or working technique per individual in a
      workgroup; (4) average number of modification types regarding psychosocial
      aspects per individual in a workgroup. RESULTS: All feedback conditions differed
      positively from controls regarding change in the proportion of workgroup members
      who reported any modification in workplace design or working technique. No such
      effect was found for psychosocial aspects. For change in average number of
      psychosocial modification types per individual in a workgroup an effect was
      observed for feedback to supervisors. No intervention effect was observed for the
      average number of modifications in workplace design or working technique per
      individual in a workgroup. CONCLUSION: Feedback and discussion of ergonomic and
      psychosocial working-environment data during one short session with individual,
      groups or supervisors of white-collar computer workers may have a positive effect
      on how many people in a workgroup modify (or have modifications done regarding)
      workplace design and working technique. Feedback to supervisors may have an
      effect on the average number of psychosocial modification types per individual in
      a workgroup. Feedback to group supervisors appeared to be the most cost-effective
      variant.

PMID- 15558303
TI  - Tingling/numbness in the hands of computer users: neurophysiological findings
      from the NUDATA study.
AB  - OBJECTIVES: To investigate whether tingling/numbness of the hands and fingers
      among computer users is associated with elevated vibration threshold as a sign of
      early nerve compression. METHODS: Within the Danish NUDATA study, vibratory
      sensory testing with monitoring of the digital vibration threshold at seven
      frequencies on the second and fifth fingers of both hands was performed on 20
      cases with unilateral tingling/numbness in the hands and fingers, and 20 gender-
      and age-matched controls. Both cases and controls were identified from
      questionnaire information about tingling/numbness at least once a week or daily
      within the last 3 months. Participants with more than slight muscular pain or
      disorders of the neck and upper extremities, excessive alcohol consumption,
      previous injuries of the upper extremities, or concurrent medical diseases were
      excluded. The two groups had a similar amount of work with mouse, keyboard, and
      computer. RESULTS: Seven of the 20 cases (35%) had elevated vibration thresholds,
      compared with 3 of the 20 controls (15%); this difference was not statistically
      significant (chi2=2.13, P=0.14). Compared with controls, cases had increased
      perception threshold for all frequencies, but the difference was statistically
      significant for only 2 out of 14 measurements. Comparison between left and right
      hand threshold values within the case group did not show any significant
      difference at any frequency. CONCLUSIONS: The results indicate that
      tingling/numbness of the hands and fingers among computer users cannot be
      explained by nerve compression.

PMID- 15558304
TI  - Peri-operative filtration of disseminated cytokeratin positive cells in patients
      with colorectal liver metastasis.
AB  - BACKGROUND: Liver resection is the only potential cure for patients with
      colorectal liver metastasis. However, more than 30% of patients will develop
      tumour recurrence, probably caused by tumour cells disseminated before or during
      surgery. As prevention of cell dissemination is barely obtainable, alternative
      concepts have to be discussed. METHODS: The potential of leukocyte adhesion
      filters for the removal of cytokeratin positive cells (CK+) from blood was
      studied in 18 patients undergoing liver resection for colorectal liver
      metastasis. Blood sampling was done via a liver venous catheter during hepatic
      mobilisation. Filtration was done with an in-line WBF2 filter system. To define
      the relation between surgery and cell release we compared patients' pre-operative
      and intra-operative blood and bone marrow (BM) samples with their CK expression
      using immunochemical staining. RESULTS: CK+ cells were detected in BM samples of
      nine of 14 patients before surgery, indicating early dissemination. In ten of 18
      patients CK+ cells were detected in blood samples during hepatic mobilisation;
      all ten patients underwent major liver surgery (R0 resection). In those patients
      recurrent disease was observed more often (P < or = 0.05). In 17 of 18 patients
      CK+ cells were not detectable after filtration procedure, which indicated cell
      adhesion to the filter medium. CONCLUSION: Liver resection due to metastasis
      leads to frequent intra-operative tumour cell shedding. As the detection of CK+
      cells is correlated with disease recurrence, modification of surgical techniques
      to prevent cell dissemination, and additional therapeutic concepts such as
      advanced filtration technology, have to be discussed.

PMID- 15558306
TI  - One of the main forces that advance all fields of scientific inquiry is the
      establishment of unifying principles.

PMID- 15558307
TI  - Identification of genes responsive to brown planthopper Nilaparvata lugens Stal
      (Homoptera: Delphacidae) feeding in rice.
AB  - The brown planthopper (Nilaparvata lugens Stal) is a rice (Oryza sativa L.)
      specific herbivore that ingests assimilates from the phloem, which leads to
      stunted growth and therefore poor yield of rice. In this study, 27 planthopper
      responsive genes in rice plants were isolated by suppression subtractive
      hybridization (SSH), and confirmed by filter cDNA array hybridization and
      northern blot analysis. Among these transcripts, 25 were induced and 2 were
      suppressed by N. lugens feeding. The responsive genes are involved in
      photosynthesis, macromolecule degradation, signal transduction and defenses
      against stress and pathogens. Overall, genes involved in macromolecule
      degradation and plant defenses were up-regulated, whereas those involved in
      photosynthesis and cell growth were down-regulated. Our data suggest that leaf
      senescence is most likely activated in the susceptible rice plants damaged by N.
      lugens insects.

PMID- 15558314
TI  - Macrocephalic mental retardation associated with a novel C-terminal MECP2
      frameshift deletion.
AB  - We report a novel C-terminal MECP2 frameshift deletion (1135_1142delCCCGTG CC) in
      a 19-year-old woman with mental retardation and epilepsy. Preservation of
      language capabilities, purposeful hand use and sufficient locomotion implied an
      atypical variant of Rett syndrome (OMIM 312750). Occipito-frontal head
      circumference was large at birth (36 cm; SDS 1.7) and increased until adulthood
      (58.5 cm; SDS 2.3). CONCLUSION: Our observation indicates that head size and head
      growth are of limited reliability in the diagnosis of MECP2-associated
      phenotypes.

PMID- 15558315
TI  - There is bullying and bullying.

PMID- 15558316
TI  - Plasma aldosterone levels in the 1st week of life in infants of less than 30
      weeks gestation.
AB  - Plasma aldosterone levels were measured in 50 infants of less than 30 weeks
      gestation at 24 h (D1) and 7 days (D7). The relationship between the plasma
      aldosterone level and a number of clinical and biochemical variables was
      explored. Plasma aldosterone levels ranged from 1000 to 30000 pmol/l and were
      inversely correlated with the severity of illness (D1 or D7), serum sodium (D7)
      and 24 h sodium intake (D1). No correlation with the serum potassium level was
      noted. CONCLUSION: Plasma aldosterone levels in this extremely premature cohort
      were significantly greater than those reported in more mature infants. Important
      determinants were severity of illness and sodium homeostasis.

PMID- 15558317
TI  - A family with pyruvate dehydrogenase complex deficiency due to a novel C>T
      substitution at nucleotide position 407 in exon 4 of the X-linked Epsilon1alpha
      gene.
AB  - The pyruvate dehydrogenase complex (PDHc; McKusick 312170), localised in the
      mitochondrial matrix, is a multienzyme complex which converts pyruvate to acetyl
      CoA. A deficiency of PDHc leads to inadequate removal of pyruvate and lactate
      resulting in lactic acidaemia and insufficient energy production. The major cause
      of PDHc deficiency is a defect in the E1alpha component. The gene of this
      component is localised to Xp22.1. We describe two brothers with a relatively mild
      clinical phenotype of PDHc deficiency. Onset of disease was associated with
      muscle weakness and swallowing difficulties in both. At follow-up, the older
      brother developed encephalopathic features consistent with Leigh syndrome.
      Lactate to pyruvate ratios were low, consistent with a PDHc deficiency which was
      confirmed by measurements of PDHc activity in thrombocytes. A 407C>T change in
      exon 4 of the E1alpha gene was found in both brothers and their mother. This
      substitution predicts a replacement of a conserved alanine at position 136 by
      valine. CONCLUSION: Due to the X-linked inheritance pattern combined with the
      overall results of clinical investigations, molecular genetic findings and a
      corresponding functional deficiency of the gene product we believe that this
      substitution in the pyruvate dehydrogenase E1alpha gene is a mutation leading to
      pyruvate dehydrogenase complex deficiency in this family.

PMID- 15558318
TI  - Microarray analysis of RpoS-mediated gene expression in Escherichia coli K-12.
AB  - The alternative sigma factor RpoS controls the expression of many stationary
      phase genes in Escherichia coli and other bacteria. Though the RpoS regulon is a
      large, conserved system that is critical for adaptation to nutrient deprivation
      and other stresses, it remains incompletely characterized. In this study, we have
      used oligonucleotide arrays to delineate the transcriptome that is controlled by
      RpoS during entry into stationary phase of cultures growing in rich medium. The
      expression of known RpoS-dependent genes was confirmed to be regulated by RpoS,
      thus validating the use of microarrays for expression analysis. The total number
      of positively regulated stationary-phase genes was found to be greater than 100.
      More than 45 new genes were identified as positively controlled by RpoS.
      Surprisingly, a similar number of genes were found to be negatively regulated by
      RpoS, and these included almost all genes required for flagellum biosynthesis,
      genes encoding enzymes of the TCA cycle, and a physically contiguous group of
      genes located in the Rac prophage region. Negative regulation by RpoS is thus
      much more extensive than has previously been recognized, and is likely to be an
      important contributing factor to the competitive growth advantage of rpoS mutants
      reported in previous studies.

PMID- 15558319
TI  - Genomic organization of the Neurospora crassa gsn gene: possible involvement of
      the STRE and HSE elements in the modulation of transcription during heat shock.
AB  - Glycogen synthase, an enzyme involved in glycogen biosynthesis, is regulated by
      phosphorylation and by the allosteric ligand glucose-6-phosphate (G6P). In
      addition, enzyme levels can be regulated by changes in gene expression. We
      recently cloned a cDNA for glycogen synthase ( gsn) from Neurospora crassa, and
      showed that gsn transcription decreased when cells were exposed to heat shock
      (shifted from 30 degrees C to 45 degrees C). In order to understand the
      mechanisms that control gsn expression, we isolated the gene, including its 5'
      and 3' flanking regions, from the genome of N. crassa. An ORF of approximately
      2.4 kb was identified, which is interrupted by four small introns (II-V). Intron
      I (482 bp) is located in the 5'UTR region. Three putative Transcription
      Initiation Sites (TISs) were mapped, one of which lies downstream of a canonical
      TATA-box sequence (5'-TGTATAAA-3'). Analysis of the 5'-flanking region revealed
      the presence of putative transcription factor-binding sites, including Heat Shock
      Elements (HSEs) and STress Responsive Elements (STREs). The possible involvement
      of these motifs in the negative regulation of gsn transcription was investigated
      using Electrophoretic Mobility Shift Assays (EMSA) with nuclear extracts of N.
      crassa mycelium obtained before and after heat shock, and DNA fragments
      encompassing HSE and STRE elements from the 5'-flanking region. While elements
      within the promoter region are involved in transcription under heat shock,
      elements in the 5'UTR intron may participate in transcription during vegetative
      growth. The results thus suggest that N. crassa possesses trans -acting elements
      that interact with the 5'-flanking region to regulate gsn transcription during
      heat shock and vegetative growth.

PMID- 15558320
TI  - Immunolocalisation of P2X and P2Y nucleotide receptors in the rat nasal mucosa.
AB  - Purinoceptor subtypes were localised to various tissue types present within the
      nasal cavity of the rat, using immunohistochemical methods. P2X3 receptor
      immunoreactivity was localised in the primary olfactory neurones located both in
      the olfactory epithelium and vomeronasal organs (VNO) and also on subepithelial
      nerve fibres in the respiratory region. P2X5 receptor immunoreactivity was found
      in the squamous, respiratory and olfactory epithelial cells of the rat nasal
      mucosa. P2X7 receptor immunoreactivity was also expressed in epithelial cells and
      colocalised with caspase 9 (an apoptotic marker), suggesting an association with
      apoptosis and epithelial turnover. P2Y1 receptor immunoreactivity was found
      within the respiratory epithelium and submucosal glandular tissue. P2Y2 receptor
      immunoreactivity was localised to the mucus-secreting cells within the VNO. The
      possible functional roles of these receptors are discussed.

PMID- 15558321
TI  - Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in
      adult human differentiated cells and certain types of kidney cancer.
AB  - Human prominin-1/CD133 has been reported to be expressed in neural and
      hematopoietic stem/progenitor cells and in embryonic, but not adult, epithelia.
      This lack of detection of human prominin-1, as defined by its glycosylation
      dependent AC133 epitope, is surprising given the expression of the murine
      ortholog in adult epithelia. Here, we demonstrate, by using a novel prominin-1
      antiserum (alphahE2), that the decrease of AC133 immunoreactivity observed during
      differentiation of the colonic adenocarcinoma-derived Caco-2 cells is not
      paralleled by a down-regulation of prominin-1. We have also shown that alphahE2
      immunoreactivity, but not AC133 immunoreactivity, is present in several adult
      human tissues, such as kidney proximal tubules and the parietal layer of Bowman's
      capsule of juxtamedullary nephrons, and in lactiferous ducts of the mammary
      gland. These observations suggest that only the AC133 epitope is down-regulated
      upon cell differentiation. Furthermore, alphahE2 immunoreactivity has been
      detected in several kidney carcinomas derived from proximal tubules, independent
      of their grading. Interestingly, in one particular case, the AC133 epitope, which
      is restricted to stem cells in normal adult tissue, was up-regulated in the
      vicinity of the tumor. Our data thus show that (1) in adults, the expression of
      human prominin-1 is not limited to stem and progenitor cells, and (2) the
      epitopes of prominin-1 might be useful for investigating solid cancers.

PMID- 15558322
TI  - Tight junction protein MAGI-1 is up-regulated by transfection with connexin 32 in
      an immortalized mouse hepatic cell line: cDNA microarray analysis.
AB  - Gap junctions are considered to play a crucial role in differentiation of
      epithelial cells, including hepatocytes. Recently, we found that Cx32 but not
      Cx26 was closely related to tight junctional proteins in primary cultured rat
      hepatocytes (Kojima et al., Exp Cell Res 263:193-201, 2001) and that Cx32
      formation and/or Cx32-mediated intercellular communication could induce
      expression and function of tight junctions in a mouse hepatic cell line (Kojima
      et al., Exp Cell Res 276:40-51, 2002). In this study, to investigate the
      mechanisms of induction of tight junctions by transfection with Cx32, we
      performed cDNA microarray analysis of Cx32 transfectants, compared with parental
      cells derived from Cx32-deficient hepatocytes. In cDNA microarray analysis, a 2.5
      fold increase in expression of membrane-associated guanylate kinase with inverted
      orientation-1 (MAGI-1), which is known to be localized at adherens and tight
      junction regions, was observed. High expression of MAGI-1 in Cx32 transfectants
      was confirmed by Western blotting and RT-PCR. MAGI-1 was colocalized with
      occludin, claudin-2, ZO-1, and F-actin, but not with E-cadherin in the apical
      most regions at cell borders of Cx32 transfectants, similar to junctional
      adhesion molecule-1 (JAM-1), which may play a crucial role in formation and
      assembly of tight junctions. Treatment with the gap junction blocker 18beta
      glycyrrhetinic acid did not affect expression of MAGI-1 and JAM-1 in Cx32
      transfectants. These results suggest that Cx32 expression is in part related to
      induction of tight junctions through modulation of MAGI-1 expression in an
      immortalized mouse hepatic cell line.

PMID- 15558323
TI  - Glucose stimulates the expression and activities of nitric oxide synthases in
      incubated rat islets: an effect counteracted by GLP-1 through the cyclic AMP/PKA
      pathway.
AB  - We have examined the expression and activity of inducible nitric oxide synthase
      (iNOS) and the activity of neuronal constitutive NOS (ncNOS) in isolated rat
      pancreatic islets, stimulated by a "hyperglycaemic" concentration of glucose, and
      whether the NOS activities could be modulated by activation of the cyclic
      AMP/protein kinase A (cyclic AMP/PKA) system in relation to the insulin secretory
      process. Here, we show that glucose stimulation (20 mmol/l) induces iNOS and
      increases ncNOS activity. No iNOS is detectable at basal glucose levels (3.3
      mmol/l). The addition of glucagon-like-peptide 1 (GLP-1) or dibutyryl-cAMP to
      islets incubated with 20 mmol/l glucose results in a marked suppression of iNOS
      expression and activity, a reduction in ncNOS activity and increased insulin
      release. The GLP-1-induced suppression of glucose-stimulated iNOS activity and
      expression and its stimulation of insulin release is, at least in part, PKA
      dependent, since the PKA inhibitor H-89 reverses the effects of GLP-1. These
      observations have been confirmed by confocal microscopy showing the glucose
      stimulated expression of iNOS, its suppression by GLP-1 and its reversion by H-89
      in beta-cells. We have also found that the NO scavenger cPTIO and the NOS
      inhibitor L-NAME potentiate the insulin response to glucose, again suggesting
      that NO is a negative modulator of glucose-stimulated insulin release. We
      conclude that the induction of iNOS and the increase in ncNOS activity caused by
      glucose in rat islets is suppressed by the cyclic AMP/PKA system. The inhibition
      of iNOS expression by the GLP-1/cyclic AMP/PKA pathway might possibly be of
      therapeutic potential in NO-mediated beta-cell dysfunction and destruction.

PMID- 15558324
TI  - Transplantation of reconstructed human skin on nude mice: a model system to study
      expression of human tenascin-X and elastic fiber components.
AB  - Tenascin-X is a large extracellular matrix protein that is widely expressed in
      connective tissues during development and in the adult. Genetically determined
      deficiency of tenascin-X causes the connective tissue disease Ehlers-Danlos
      syndrome. These patients show reduced collagen density and fragmentation of
      elastic fibers in their skin. In vitro studies on the role of tenascin-X in
      elastic fiber biology are hampered because monolayers of fibroblasts do not
      deposit tenascin-X and elastic fibers into the extracellular matrix. Here, we
      applied an organotypic culture model of fibroblasts and keratinocytes to address
      this issue. We investigated the deposition of tenascin-X and elastin into skin
      equivalent in vitro and also in vivo after transplantation onto immunodeficient
      mice. Whereas tenascin-C and fibrillin-1 were readily expressed in the skin
      equivalents before transplantation, tenascin-X and elastin were not present.
      Three weeks post-grafting, a network of elastin was observed that coincided with
      the appearance of tenascin-X. At the ultrastructural level, microfibrils were
      observed, some of which were associated with elastin. Transplanted skin
      equivalents containing tenascin-X-deficient fibroblasts showed deposition of
      immunoreactive elastin in similar quantities and distribution as those containing
      control fibroblasts. This suggests that tenascin-X is important for the stability
      and maintenance of established elastin fibers, rather than for the initial phase
      of elastogenesis. Thus, the transplantation of reconstructed skin on nude mice
      allows the study of tenascin-X and elastin expression and could be used as a
      model system to study the potential role of tenascin-X in matrix assembly and
      stability.

PMID- 15558325
TI  - Changes in the distribution of ZO-1, occludin, and claudins in the rat uterine
      epithelium during the estrous cycle.
AB  - During the estrous cycle, the endometrium epithelium experiences marked cellular
      structural changes. For fertilization to proceed, maintenance of an adequate
      uterine environment by ovarian hormones is essential. Epithelial cells lining the
      uterine lumen are associated with each other by tight junctions (TJs), which
      regulate the passage of ions and molecules through the paracellular pathway. The
      aim of the present study was to assess by confocal immunofluorescence the
      distribution pattern of the TJ proteins ZO-1, occludin, and claudins 1-7 in the
      rat uterus during the estrous cycle. Our results reveal that on proestrus, the
      day when mating takes place, ZO-1, occludin, and claudins 1 and 5 are located in
      the TJs, while claudins 3 and 7 display a basolateral distribution. In contrast,
      on metestrus day, when no sexual mating occurs and the uterine lumen is devoid of
      secretions, none of these proteins were detected in the TJ region, and only a
      diffuse cytosolic staining was observed for some of the proteins. On estrus and
      diestrus days, an intermediate situation was encountered, since ZO-1 localized in
      the TJs, whereas occludin was no longer detectable in the TJs. The distribution
      of claudins during these stages varied from the lowermost portion of the
      basolateral membrane to its apex. In conclusion, the results show that the
      protein composition of TJs present in the luminal epithelial cells of the uterus
      changes during the different days of the estrous cycle, and suggest that the
      expression of TJ proteins participates in providing an adequate environment for a
      successful fertilization.

PMID- 15558326
TI  - Interactive effects of elevated CO2, N deposition and climate change on plant
      litter quality in a California annual grassland.
AB  - Although global changes can alter ecosystem nutrient dynamics indirectly as a
      result of their effects on plant litter quality, the interactive effects of
      global changes on plant litter remain largely unexplored in natural communities.
      We investigated the effects of elevated CO2, N deposition, warming and increased
      precipitation on the composition of organic compounds in plant litter in a fully
      factorial experiment conducted in a California annual grassland. While lignin
      increased within functional groups under elevated CO2, this effect was attenuated
      by warming in grasses and by water additions in forbs. CO2-induced increases in
      lignin within functional groups also were counteracted by an increase in the
      relative biomass of forbs, which contained less lignin than grasses.
      Consequently, there was no net change in the overall lignin content of senesced
      tissue at the plot level under elevated CO2. Nitrate additions increased N in
      both grass and forb litter, although this effect was attenuated by water
      additions. Relative to changes in N within functional groups, changes in
      functional group dominance had a minor effect on overall litter N at the plot
      level. Nitrate additions had the strongest effect on decomposition, increasing
      lignin losses from Avena litter and interacting with water additions to increase
      decomposition of litter of other grasses. Increases in lignin that resulted from
      elevated CO2 had no effect on decomposition but elevated CO2 increased N losses
      from Avena litter. Overall, the interactions among elements of global change were
      as important as single-factor effects in influencing plant litter chemistry.
      However, with the exception of variation in N, litter quality had little
      influence on decomposition over the short term.

PMID- 15558327
TI  - Prompt control of bronchorrhea in patients with bronchioloalveolar carcinoma
      treated with gefitinib (Iressa).
AB  - Bronchorrhea is a condition in which voluminous sputum is produced daily,
      typically seen with bronchioloalveolar cell carcinoma (BAC). Unless the
      underlying cancer can be controlled, bronchorrhea causes substantial symptomatic
      distress. We report two cases of bronchorrhea associated with advanced BAC
      successfully treated with the epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor, gefitinib. Prompt resolution of these patients' bronchorrhea,
      dyspnea, and supplemental oxygen requirements are detailed. Given the limited
      success of alternative interventions, a trial of gefitinib should be considered
      for patients with bronchorrhea secondary to BAC.

PMID- 15558328
TI  - Role of nutrient level and defoliation on symbiotic function: experimental
      evidence by tracing 14C/15N exchange in mycorrhizal birch seedlings.
AB  - High nutrient availability and defoliation generally reduce ectomycorrhizal
      colonization levels in trees, but it is not known how this affects the functional
      aspects of mycorrhizal symbiosis. It was therefore investigated whether (1)
      defoliation or increasing substrate N availability reduce C allocation from the
      plant to the fungus and N allocation from the fungus to the plant (symbiotic
      resource exchange), (2) symbiotic resource exchange depends on relative N and P
      availability, and (3) fungal N translocation to plant and plant C allocation to
      fungus are interdependent. Birch (Betula pendula) seedlings were grown in
      symbiosis with the ectomycorrhizal fungus Paxillus involutus at five times excess
      N, or at five times excess N and P for 6 weeks. One-half of the plants were
      defoliated and the plant shoots were allowed to photosynthesize 14CO2 while the
      fungal compartment was exposed to 14NH4. After 3 days, the 14C of plant origin in
      fungal tissues and 15N of fungal origin in plant tissues were quantified.
      Nutrient availability had no observable effect on symbiotic resource exchange in
      non-defoliated systems. Defoliation reduced symbiotic N acquisition by plants at
      all levels of nutrient availability, with the reduction being most marked at
      higher N availability, indicating an increased tendency in the symbiotic system
      to discontinue resource exchange after defoliation at higher fertility levels.
      The concentration of 14C in extramatrical mycelium correlated significantly with
      the concentration of 15N in birch shoots. The results support the assumption that
      N delivery to the host by the mycorrhizal fungus is dependent on C flow from the
      plant to the fungus, and that exchanges between the partners are reciprocal. No
      significant reductions in root 14C content as a response to defoliation were
      observed, indicating that defoliation specifically reduced allocation to fungus,
      but not markedly to roots.

PMID- 15558330
TI  - Characterisation of new symbiotic Medicago truncatula (Gaertn.) mutants, and
      phenotypic or genotypic complementary information on previously described
      mutants.
AB  - From a pool of Medicago truncatula mutants--obtained by gamma-irradiation or
      ethyl methanesulfonate mutagenesis--impaired in symbiosis with the N-fixing
      bacterium Sinorhizobium meliloti, new mutants are described and genetically
      analysed, and for already reported mutants, complementary data are given on their
      phenotypic and genetic analysis. Phenotypic data relate to nodulation and
      mycorrhizal phenotypes. Among the five new mutants, three were classified as
      [Nod+ Fix- Myc+] and the mutations were ascribed to two loci, Mtsym20 (TRV43,
      TRV54) and Mtsym21 (TRV49). For the two other new mutants, one was classified as
      [Nod-/+ Myc+] with a mutation ascribed to gene Mtsym15 (TRV48), and the other as
      [Nod- Myc-/+] with a mutation ascribed to gene Mtsym16 (TRV58). Genetic analysis
      of three previously described mutants has shown that [Nod-/+ Myc+] TR74 mutant
      can be ascribed to gene Mtsym14, and that [Nod-/+ Myc-/+] TR89 and TRV9 mutants
      are ascribed to gene Mtsym2 (dmi2). Using a detailed analysis of mycorrhizal
      phenotype, we have observed a delayed typical arbuscular mycorrhizal formation on
      some mutants that present thick lens-shaped appressoria. This phenotype was
      called [Myc-/+] and mutants TR25, TR26, TR89, TRV9, P1 and Y6 were reclassified
      as [Myc-/+]. Mutant P1 was reclassified as [Nod-/+] because of a late nodulation
      observed on roots of this mutant.

PMID- 15558329
TI  - Gene expression of the ericoid mycorrhizal fungus Oidiodendron maius in the
      presence of high zinc concentrations.
AB  - A heavy metal tolerant strain of the ericoid mycorrhizal species Oidiodendron
      maius, isolated from roots of Vaccinium myrtillus growing in soil heavily
      contaminated with zinc, was previously shown to tolerate high concentrations of
      zinc and cadmium ions in the growth medium. We have investigated the genetic
      basis of this fungal strain tolerance to high zinc concentrations by using an
      untargeted approach. From a cDNA library constructed by using mRNA from Zn
      treated O. maius mycelia, 444 clones were randomly selected and 318 were
      sequenced. Sequence analysis identified 219 unique clones: 117 showed homology to
      previously identified genes, 26 matched unknown protein coding regions found in
      other organisms, and 76 were novel. Variation in the gene expression level after
      a 20-day treatment with high concentrations of Zn was monitored on 130 unigenes
      by reverse northern blot hybridisation. Sixteen unigenes were shown to be either
      up- (9) or down- (7) regulated. The putative function of these genes and their
      involvement in stress tolerance is discussed.

PMID- 15558331
TI  - Development of the oxygenator: past, present, and future.
AB  - From the 1950s to the 1980s, the most widely used oxygenator in the clinical
      field was the disposable bubble oxygenator. However, membrane oxygenators have
      become the preferred clinical choice over the years. In the United States,
      membrane oxygenators used in cardiopulmonary bypass operations account for the
      majority of clinical oxygenator use. Membrane oxygenators have an equal
      capability for oxygenating venous blood compared with other type of oxygenators
      such as the bubble type and film type; however, the membrane oxygenator requires
      a smaller volume for priming to achieve a sufficient gas transfer rate and
      results in less blood trauma such as hemolysis because it uses a similar
      mechanism to the natural lung. In the 1980s, the first capillary-type oxygenator
      adopted the system of intracapillary blood perfusion. However, this induced high
      pressure resistance in the module and caused hemolysis. Thus, at present,
      capillary oxygenators commonly adopt the system of extracapillary blood
      perfusion. Microporous hollow-fiber membranes are primarily used for short-term
      cardiopulmonary bypass application, whereas nonmicroporous hollow-fiber membranes
      are primarily used for long-term extracorporeal membrane oxgenation application.

PMID- 15558332
TI  - Observation of cavitation bubbles in monoleaflet mechanical heart valves.
AB  - Recently, cavitation on the surface of mechanical heart valves (MHVs) has been
      studied as a cause of fractures occurring in implanted MHVs. In the present
      study, we investigated the mechanism of MHV cavitation associated with the Bjork
      Shiley valve and the Medtronic Hall valve in an electrohydraulic total artificial
      heart (EHTAH). The valves were mounted in the mitral position in the EHTAH. The
      valve closing motion, pressure drop measurements, and cavitation capture were
      employed to investigate the mechanisms for cavitation in the MHV. There are no
      differences in valve closing velocity between the two valves, and its value
      ranged from 0.53 to 1.96 m/s. The magnitude of negative pressure increased with
      an increase in the heart rate, and the negative pressure in the Medtronic Hall
      valve was greater than that in the Bjork-Shiley valve. Cavitation bubbles were
      concentrated at the edge of the valve stop; the major cause of these cavitation
      bubbles was determined to be the squeeze flow. The formation of cavitation
      bubbles depended on the valve closing velocity and the valve leaflet geometry.
      From the viewpoint of squeeze flow, the Bjork-Shiley valve was less likely to
      cause blood cell damage than the Medtronic Hall valve in our EHTAH.

PMID- 15558333
TI  - Clinical results of open stent grafting applied using an improved endotracheal
      tube in the treatment of high-risk patients with distal arch aneurysms.
AB  - Whereas the operative results for thoracic aortic aneurysms (TAA) have improved
      in recent years, the results for distal arch aneurysms (DAA) remain
      unsatisfactory. We report herein the initial results of open stent grafting (OSG)
      applied using an improved endotracheal tube for surgical treatment of high-risk
      DAA. OSG was used to treat DAA in five men aged 69-80 years (mean, 77 years).
      Four cases involved chronic obstructive pulmonary disease, and the remaining case
      involved both ischemic heart disease and chronic renal failure. Previous surgical
      repairs of an abdominal aortic aneurysm had been performed in four patients, and
      thoracoplasty and reconstruction of the lower extremities had been performed in
      the remaining patient. Under selective cerebral perfusion, OSG with
      revascularization of two cerebral branches was performed in two patients, whereas
      OSG with total arch replacement was performed in three patients. The procedure
      was successful in all cases. There were no complications related to cerebrospinal
      disorders, and complete thrombosis of the aneurismal sac was achieved in all
      cases. The new deployment method using an endotracheal tube offers numerous
      advantages, including reduced aortic wall injury and accurate placement of the
      stent graft in the operative field. These initial results suggest that this
      specific approach makes OSG a useful surgical procedure in the treatment of high
      risk DAA.

PMID- 15558334
TI  - Effect of the elastic conditions around a stentless valvular bioprosthesis on
      opening behavior.
AB  - Stentless valvular bioprostheses have been used clinically for over 8 years and
      the excellent properties of the bioprostheses have been demonstrated in clinical
      studies. The present study examined how differing elastic conditions around the
      bioprosthesis at the aortic position affect the hydrodynamic characteristics of
      the bioprosthesis. Bioprosthesis implantation is typically performed using either
      the subcoronary or the full-root technique. These procedures for implanting a
      stentless prosthetic heart valve at the aortic root were hydrodynamically
      evaluated in a mock circulatory system. Forward flow rate was 11% greater with
      the subcoronary technique than with the full-root technique. In a high-speed
      video camera study, the orifice area at full opening was 12% larger for the
      subcoronary technique than for the full-root technique. Evaluation of
      bioprosthetic characteristics in terms of mechanical conditions is important when
      considering surgical options.

PMID- 15558335
TI  - Nano-scaled hydroxyapatite/polymer composite IV. Fabrication and cell adhesion
      properties of a three-dimensional scaffold made of composite material with a silk
      fibroin substrate to develop a percutaneous device.
AB  - Nano-scaled sintered hydroxyapatite (HAp) particles with an a-axis length of 87
      +/- 23 nm, a c-axis length of 236 +/- 81 nm, and a mean aspect ratio ( c/ a) of
      2.72 were covalently linked onto a silk fibroin (SF) substrate chemically
      modified by graft polymerization with gamma-methacryloxypropyl trimethoxysilane
      (MPTS). Graft polymerization with poly(MPTS) on SF was conducted by free-radical
      initiation in a water solvent with pentaethylene glycol dodecyl ether as a
      nonionic surfactant. The alkoxysilyl groups of the graft polymers avoided
      hydrolysis and maintained their activity in coupling with the hydroxyl groups on
      the HAp surface despite the use of water as the reaction solvent. The weight gain
      of poly(MPTS) on SF increased with increasing the reaction time, eventually
      reaching a plateau value of about 15 wt% after 50 min of reaction time. After HAp
      covalent coating, the particles separated or aggregated into several crystals, as
      shown by scanning electron microscopic observation. L929 fibroblast cells adhered
      more plentifully on HAp-coated SF compared to untreated SF and hydrolyzed
      poly(MPTS)-grafted SF during 24 h or 48 h of incubation. The cells adhered only
      on the HAp surface but not at all on the dehydrated grafted surface of SF without
      HAp. A button-shaped prototype for a percutaneous device was manufactured by
      transplantation of HAp-coated SF fibers of about 100 microm in length onto
      silicone moldings using an adhesive, and the device showed good cell
      adhesiveness.

PMID- 15558336
TI  - Myocardial microvascular perfusion after transfusion of liposome-encapsulated
      hemoglobin evaluated in cross-circulated rat hearts using tracer digital
      radiography.
AB  - The effect of hemodilution with Neo Red Cell (NRC, liposome-encapsulated
      hemoglobin) on myocardial perfusion was evaluated in cross-circulated rat hearts
      under 300-bpm pacing and 100-mmHg perfusion pressure. In NRC-transfused hearts (n
      = 5), NRC volume fraction and hematocrit were 9% +/- 3% and 22% +/- 4%,
      respectively; the latter decreased from 43% +/- 3% before NRC transfusion.
      Coronary perfusion rate and left ventricular isovolemic developed pressure
      increased after NRC transfusion to 4.6 +/- 1.0 ml/min/g and 127 +/- 32 mmHg from
      basal values of 2.5 +/- 0.3 ml/min/g and 115 +/- 28 mmHg, respectively. In
      contrast, the flow increase during reperfusion following 30-s flow cessation
      decreased from 74% +/- 24% to 64% +/- 24%. The arteriovenous difference in O2
      saturation was slightly higher after NRC transfusion. Within-layer regional flow
      distributions from subepicardium to subendocardium assessed by tracer digital
      radiography (100-microm resolution) showed that coefficients of variation of
      flows in 400 x 400-microm regions were 0.41 +/- 0.10 in NRC-transfused hearts and
      0.54 +/- 0.11 in nontransfused hearts (n = 5); i.e., the myocardial flow
      distribution was more uniform in NRC-transfused hearts. These results suggest
      that NRC is superior to erythrocytes in terms of the homogenization of O2
      delivery, indicating its potential therapeutic value in myocardial
      microcirculatory failure.

PMID- 15558337
TI  - Development of a dialyzer with enhanced internal filtration to increase the
      clearance of low molecular weight proteins.
AB  - Accumulated low molecular weight proteins in hemodialysis patients require a high
      flux dialyzer. There have been several methods proposed for enhancing internal
      filtration, including narrowing the inside diameter of the hollow fibers,
      lengthening the fibers, and increasing the fiber density ratio. We tried to
      enhance the internal filtration by increasing the pressure drop in the dialysate
      compartment through increasing the fiber density ratio. If the fiber density
      ratio is too high, however, an irregular dialysate path may result, thus
      decreasing dialysis performance. Therefore, we took note of the shape of the
      inner housing and added a short taper structure, which improved the dialysate
      path dramatically. Consequently, we developed an internal filtration-enhanced
      dialyzer (APS-Prototype) to improve dialysis performance. The internal filtration
      rate in water (measured by Doppler ultrasound) was 13.2 l/session for the APS
      Prototype and 5.3 l/session for the APS-15E. The amount of alpha1-microglobulin
      (alpha1-MG) in bovine plasma was 0.34 g for the APS-Prototype and 0.11 g for the
      APS-15E. In addition, the amount of alpha1-MG in vivo was 29.0% +/- 5.8% for the
      APS-Prototype, significantly higher than that for the APS-15E (13.6% +/- 1.9%).
      The desirable loss of albumin is 2-4 g in hemodiafiltration, and it was 3.92 +/-
      1.03 g for the APS-Prototype. The prototype showed excellent solute removal
      performance with no clinical or engineering problems.

PMID- 15558338
TI  - Synergistic cytotoxicity of acidity and glucose degradation products in
      peritoneal dialysis fluid.
AB  - Of the nonphysiological compounds in glucose-rich peritoneal dialysate, we
      investigated the cytotoxicity and synergistic cytotoxicity of acidity and glucose
      degradation products (GDPs) using human peritoneal mesothelial cells (HPMC). The
      effect of pH on cell viability was examined by adding 1N HCl to a phosphate
      buffered solution (pH > or = 5.5). We also examined the cytotoxic effects of
      various GDPs [glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3DG),
      alone or in combination] and pH (5.5 or 6.7). The cells were exposed to these
      solutions for 2 or 4 h. Cell viability was determined by 3,(4,5-dimethylthiazol-2
      yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. Although the MTT viability of
      HPMC was not decreased by GDP or acidity alone, the combination of acidity and
      GDP markedly decreased MTT viability, strongly suggesting the synergistic
      cytotoxicity of GDP and acidity.

PMID- 15558339
TI  - Nonocclusive mesenteric ischemia after cardiopulmonary bypass.
AB  - Nonocclusive mesenteric ischemia (NOMI) is a rare abdominal pathology caused by
      mucosal hypoperfusion without actual obstruction to the mesenteric arteries. We
      present a case of NOMI after a cardiopulmonary bypass operation. The patient was
      a 79-year-old woman with a history of hypertension and diabetes mellitus. A
      coronary bypass operation was performed with stable hemodynamic conditions, and
      continuous venovenous hemodialysis was performed on the second postoperative day
      because of renal insufficiency. After 24 h of hemodialysis, the hematocrit level
      increased from 29.1% to 36.1%. The patient had some vague abdominal pain on the
      third postoperative day with abnormal laboratory values: leukocytes 17.10 x
      10(3)/microl, creatine kinase 1085 U/l, glutamic-oxyloacetic transaminase 6188
      U/l, and lactate dehydrogenase 8695 U/l. Selective angiography showed diffuse
      stenosis of the superior mesenteric artery (SMA) without any occlusive findings
      on the major branches; the patient was therefore diagnosed with NOMI. An infusion
      of urokinase and prostaglandin E1 was started; however, disseminated
      intravascular coagulopathy had developed and the patient died on the 21st
      postoperative day as a result of multiple organ failure. The autopsy demonstrated
      extensive necrosis and hemorrhage in the small intestine without any occlusive
      findings on the major branches of the SMA.

PMID- 15558340
TI  - Delayed maturation of IgG avidity in congenital toxoplasmosis.
AB  - The aim of this comparative study was to investigate the clinical usefulness of
      the measurement of Toxoplasma gondii IgG avidity in the postnatal diagnosis of
      congenital toxoplasmosis. IgG avidity values in serum samples from infants with
      congenital infection were compared with those in samples from uninfected infants,
      all born to mothers with toxoplasmosis acquired during gestation. This analysis
      revealed that IgG avidity values soon after birth reflected maternal values in
      the large majority of the samples. Low or borderline IgG avidity values were
      systematically found in the cohort of congenitally infected subjects. After
      birth, IgG avidity values slowly increased over time for up to 2 years in
      congenitally infected subjects. On the contrary, IgG avidity values in the
      uninfected infants remained stable over time. The presence of low IgG avidity in
      a newborn can be considered a marker of maternal seroconversion in the second or
      third trimester of gestation and, as a consequence, an indicator of risk for
      congenital toxoplasmosis. An IgG avidity assay can be easily carried out with
      antibodies eluted from dried blood spots (Guthrie cards), providing an
      opportunity to retrospectively evaluate the risk of congenital infection in
      special clinical circumstances, for example when suspicion of congenital
      infection arises during late infancy.

PMID- 15558341
TI  - Pseudallescheria boydii cranial osteomyelitis and subdural empyema successfully
      treated with voriconazole: a case report and literature review.
AB  - Described here is a case of Pseudallescheria boydii cranial osteomyelitis and
      subdural empyema following craniotomy, which was successfully treated with
      surgical debridement and voriconazole. Other reported cases of Pseudallescheria
      boydii osteomyelitis are reviewed. The reported case suggests that voriconazole
      may represent a new therapeutic option for this infection.

PMID- 15558342
TI  - A foodborne outbreak of Salmonella enterica subsp. enterica serovar Madelia at a
      silver anniversary reception.
AB  - Reported here is an outbreak of Salmonella enterica subsp. enterica serovar
      Madelia infection that occurred among 44 persons attending a silver anniversary
      reception in Hesse, Germany. Isolates of Salmonella Madelia are extremely
      unusual, and no outbreaks associated with this serotype have been reported
      previously. Forty-two attendees were interviewed and information was obtained
      from each of them regarding demographic and clinical characteristics and food
      consumed at the reception. Twenty-four attendees submitted stool samples for
      microbiological testing, and 10 of these were culture-positive for S. Madelia.
      Twenty-three attendees met the case definition of infection, while 18 met the
      clinical case definition (i.e. vomiting or diarrhoea within 3 days of consuming
      food at the reception) and five had asymptomatic infection with S. Madelia. The
      most likely vehicles of infection were tortellini and a red pesto sauce.

PMID- 15558343
TI  - Coombs-negative severe haemolytic anaemia in an immunocompetent adult following
      cytomegalovirus infection.
AB  - Severe haemolysis is a rare, but potentially life-threatening, complication of
      cytomegalovirus (CMV) infection in immunocompetent adults. Treatment with
      steroids or immunoglobulins, or even splenectomy, may be justified when an
      autoimmune mechanism can be identified as the cause of the anaemia. Described
      here is the case of a previously healthy patient who presented with severe
      haemolytic anaemia following CMV infection. The patient's haemoglobin level fell
      to 5.1 g/dl while extensive testing for an autoimmune mechanism remained
      negative. The patient made a slow but full recovery without additional medication
      or blood transfusions. This case demonstrates that severe haemolytic anaemia
      following CMV infection is possible even when presently available tests fail to
      show autoimmune positivity. In immunocompetent subjects a wait and see policy,
      with supportive care when necessary, is likely to be justified.

PMID- 15558344
TI  - Efficient method for mycobacterial DNA extraction in blood cultures aids rapid
      PCR identification of Mycobacterium tuberculosis and Mycobacterium avium.
AB  - The study presented here evaluated the utility of several methods of extracting
      mycobacterial nucleic acids from positive blood culture samples and examined the
      effect of each method on the performance of an in-house PCR used directly in the
      peripheral blood of 80 patients with AIDS to identify Mycobacterium spp. The
      modified Boom method for extracting DNA from blood cultures proved to be the most
      efficient, with subsequent PCR analysis yielding 100% positivity (7 samples
      positive for M. avium and 5 for M. tuberculosis). Only three of 12 patients with
      a positive blood culture had a PCR result positive for M. avium in peripheral
      blood. The identification of mycobacteria by PCR in blood culture took about 3
      days, reducing the time to diagnosis by several weeks. These results demonstrate
      that PCR is a sensitive and quick method for identifying mycobacteria, especially
      when a good DNA extraction method is applied.

PMID- 15558345
TI  - Increasing incidence of imported schistosomiasis in Mallorca, Spain.

PMID- 15558346
TI  - Nosocomial lower respiratory tract infections: prevalence and risk factors in 14
      Greek hospitals.
AB  - Nosocomial lower respiratory tract infections (NLRTIs) are associated with
      significant morbidity and mortality. The aim of this study was to investigate the
      epidemiological features of NLRTIs in Greece, where knowledge about these
      infections is limited. Two point-prevalence studies of hospital-acquired
      infections were carried out in 14 Greek hospitals located throughout the country,
      one in 1999 and one in 2000. NLRTIs were diagnosed in accordance with the Centers
      for Disease Control and Prevention (CDC) definitions. Among the 7,120
      hospitalized patients registered during the two studies, 610 (8.6%) cases of
      hospital-acquired infections were identified, of which 200 (32.8%) were NLRTIs.
      Sixty-nine (34.5%) patients had pneumonia, and the remaining 131 (65.5%) patients
      had bronchitis. The greatest prevalence of NLRTI was found in the adult ICUs
      (30.4%). Male gender, age >65 years, mechanical ventilation, tracheostomy, an
      intravenous central line, and an indwelling urethral catheter were the main risk
      factors. There was no significant difference in the incidence of NLRTI among
      hospital-acquired infections between the 1999 study and the 2000 study. The
      causative microorganism was identified in 78 of 200 (39%) cases, and 103 strains
      were isolated. The majority of strains (67%) were gram-negative bacteria. The
      most frequently isolated microorganisms were Pseudomonas aeruginosa (22.3%),
      Acinetobacter spp. (19.4%), Klebsiella pneumoniae (12.6%), and Staphylococcus
      aureus (10.7%). There was no difference between the two prevalence studies in the
      frequency of isolation of the microorganisms. NLRTI was the leading cause of
      morbidity and mortality among hospitalized patients with hospital-acquired
      infections in Greek hospitals. Gram-negative microorganisms were the most
      frequently isolated pathogens.

PMID- 15558347
TI  - Molecular detection of Bartonella quintana DNA in the dental pulp of a homeless
      patient.
AB  - Dental pulp has been proposed as a suitable tissue sample for the identification
      of pathogenic organisms. Using PCR with two specific gene targets, Bartonella
      quintana DNA was detected in the dental pulp extracted from the tooth of a
      homeless patient. The patient had been bacteremic 6 months previously but was not
      when the tooth was sampled.

PMID- 15558348
TI  - Solitary cerebral metastases from ovarian epithelial carcinoma: 11 cases.
AB  - Ovarian cancer is quite common in women, but brain metastases from ovarian cancer
      are considered rare. Eleven patients with solitary cerebral metastasis from
      ovarian epithelial carcinoma were treated at the Neurosurgical Department of
      University of Rome La Sapienza, between 1980 and 2000. We treated all of the 11
      patients by surgical en bloc removal and by postoperative radiotherapy and
      chemotherapy. Mean survival was 28 months, and the cause of death was recurrence
      of the systemic disease in all cases. Multimodal treatment by surgery, radiation
      and chemotherapy is the best choice of treatment and leads to a median survival
      of about 20 months.

PMID- 15558349
TI  - Antifungal and sprout regulatory bioactivities of phenylacetic acid, indole-3
      acetic acid, and tyrosol isolated from the potato dry rot suppressive bacterium
      Enterobacter cloacae S11:T:07.
AB  - Enterobacter cloacae S11: T:07 (NRRL B-21050) is a promising biological control
      agent that has significantly reduced both fungal dry rot disease and sprouting in
      laboratory and pilot potato storages. The metabolites phenylacetic acid (PAA),
      indole-3-acetic acid (IAA), and tyrosol (TSL) were isolated from S11:T:07 liquid
      cultures provided with three different growth media. The bioactivities of these
      metabolites were investigated via thin-layer chromatography bioautography of
      antifungal activity, wounded potato assays of dry rot suppressiveness, and cored
      potato eye assays of sprout inhibition. Relative accumulations of PAA, IAA, and
      TSL in cultures were nutrient dependent. For the first time, IAA, TSL, and PAA
      were shown to have antifungal activity against the dry rot causative pathogen
      Gibberella pulicaris, and to suppress dry rot infection of wounded potatoes.
      Disease suppression was optimal when all three metabolites were applied in
      combination. Dosages of IAA that resulted in disease suppression also resulted in
      sprout inhibition. These results suggest the potential for designing culture
      production and formulation conditions to achieve a dual purpose biological
      control agent able to suppress both dry rot and sprouting of stored potatoes.

PMID- 15558350
TI  - Detection of mature collagen in human dental enamel.
AB  - Mature dental enamel is the most mineralized of all mammalian tissues and
      considered to be free of collagen. Hydroxylysylpyridinoline (HP) and
      lysylpyridinoline (LP) are two nonreducible cross-links of mature collagen.
      Hydroxyproline (Hyp) is an amino acid that is believed to be indicative of the
      presence of collagen. We set out to assess the concentrations of Hyp, HP, and LP
      in dental enamel and dentin (control) to clarify whether there was minor collagen
      content in dental enamel. We studied 17.53 g of enamel and 22.12 g of dentin
      gained from 120 extracted human teeth. Enamel and dentin (control) were separated
      with a diamond dental drill under microscopic control by wasting a margin of
      enamel (Ca. 2 mm) at the dentin-enamel border. Collagen alpha-chains were
      analyzed by Sodium dodecylsulfate-polyacrylamide gel (SDS-PAGE) after
      decalcification and collagen extraction. Concentrations of HP and LP where
      measured by using high-performance liquid chromatography (HPLC). Hyp was analyzed
      by a spectrophotometric method. The pooled probe of enamel contained 0.23 mug/g
      of Hyp. This concentration was 49 times lower than that in dentin. Concentrations
      of HP and LP in enamel were 0.07 nmol/g and 0.02 nmol/g, respectively being
      605.57 (HP) and 251.50 (LP) times lower in enamel as compared to dentin. Collagen
      type I was found in enamel; collagen types I and V were found in dentin samples.
      In reports of many studies and textbooks, collagen is considered to be completely
      absorbed in the course of the mineralization and maturation of dental enamel. We
      show that this is not the case. However, the concentration of collagen in enamel
      was considerably lower as compared to that in dentin.

PMID- 15558351
TI  - Integrated method for single-cell DNA extraction, PCR amplification, and
      sequencing of ribosomal DNA from harmful dinoflagellates Cochlodinium
      polykrikoides and Alexandrium catenella.
AB  - A simplified technique was developed for DNA sequence-based diagnosis of harmful
      dinoflagellate species. This protocol integrates procedures for DNA extraction
      and polymerase chain reaction (PCR) amplification into a single tube. DNA
      sequencing reactions were performed directly, using unpurified PCR products as
      the DNA template for subsequent sequencing reactions. PCR reactions using DNA
      extracted from single cells of Cocodinium polykrikoides and Alexandrium catenella
      successfully amplified the target ribosomal DNA regions. DNA sequencing of the
      unpurified PCR products showed that DNA sequences corresponded to the expected
      locus of ribosomal DNA regions of both A. catenella and C. polykrikoides (each
      zero genetic distance and 100% sequence similarity). Using the protocol described
      in this article, there was little DNA loss during the purification step, and the
      technique was found to be rapid and inexpensive. This protocol clearly resolves
      the taxonomic ambiguities of closely related algal species (such as Alexandrium
      and Cochlodinium), and it constitutes a significant breakthrough for the
      molecular analysis of nonculturable dinoflagellate species.

PMID- 15558352
TI  - [The importance of exercise testing for the functional assessment of lung
      resectional candidates].
AB  - Although there are a lot of physiologic tests to evaluate the preoperative cardio
      pulmonary reserve in the patients who candidate lung resection, there is no a
      single gold standard test to suggest the postoperative pulmonary complications.
      In this study, we researched the importance of the exercise testing in the
      evaluation preoperative cardio-pulmonary reserve. We analyzed a series of 26
      consecutive patients with a resectable lung disease [26 male patients, mean age
      51.5 +/- 15.8 (13-78 years), 22 non-small cell lung carcinoma (NSCLC), 2
      bronchectasis, 1 hydatid cyst, 1 empyema]. Patients were evaluated by pulmonary
      function testing (PFT), diffusing capacity of lung for carbonmonoxide (DLCO), and
      symptom-limited exercise testing. After the functional examination, 26 patients
      underwent pulmonary resections with standard thoracotomy: 4 segmental or wedge
      resection, 11 lobectomies, 5 pneumonectomies, and 1 cystotomia. The mean stay in
      the ICU was 2.6 days (+/- 3.5), the mean hospital stay was 11.9 days (+/- 8.0).
      Postoperative complications (within 30 days) occurred in 9 (34.6%) patients of
      whom one died (overall mortality rate was 3.8%). There was no relationship
      between the presence of complication and physiologic tests (PFT, DLCO). The
      patients were divided three groups according to peak oxygen consumption (VO(2)/kg
      peak) (mL/kg/min) (< 10, 10-20, > 20 mL/kg/min). There was no significantly
      difference among these groups and complication rates (p= 0.056), but the
      complication rate was higher in the group of VO(2)/kg peak < 10 mL/kg/min (75%).
      On the other hand, there was a significantly relationship between the presence of
      only pulmonary complication and VO2/kg peak (p= 0.034). CONCLUSION: We think that
      the preoperative functional evaluation in the patients with lung resection
      candidate is prominent to reduce the postoperative mortality and morbidity and
      especially cardiopulmonary exercise testing has an important role to suggest the
      postoperative pulmonary complications as a major complication.

PMID- 15558353
TI  - [The comparison of the result of exercise bronchoprovocation test and
      methacholine bronchoprovocation test in athletes].
AB  - The excess contraction respond of the bronchiols to the specific and non-specific
      agent is called bronchial hyperresponsiveness. In our study we compared the
      result of exercise bronchoprovocation test and methacholine bronchoprovocation
      test in athletes (group I) and in sedentary subjects (group II). The subjects
      that their age, height, weight and environmental status of the test room
      (temperature and humidity) were not statistically different, they gave
      statistically different respond to the methacholine bronchoprovocation test (p<
      0.05). Their respond to exercise bronchoprovocation test was similar and there
      was no statistically difference between two groups (p> 0.05). In group I, there
      was a correlation in the result of exercise bronchoprovocation test and
      methacholine bronchoprovocation test (r= 0.60, p< 0.05), but in group II there
      was no correlation in this two tests. The parameters that we use for evaluation
      of the allergic status (total IgE, eosinophil count, number of atopic subject in
      groups) were not statistically different (p> 0.05). In both two groups there was
      a statistically different respond in the result of exercise bronchoprovocation
      test and methacholine bronchoprovocation test. These findings suggests that
      methacholine bronchoprovocation test is a more sensitive test for the diagnosis
      of BHR in athletes and sedantery subjects than exercise bronchoprovocation test.

PMID- 15558354
TI  - Effects of prognostic factors and treatment on survival in advanced non-small
      cell lung cancer.
AB  - In this study, 304 stage III-B and IV non-small cell lung cancer (NSCLC) cases
      diagnosed and followed up in our hospital between January 2000 and December 2002
      are retrospectively analysed. The effects of demographic, clinical, laboratory
      findings and different therapeutic modalities on survival were investigated. Of
      the cases, 31 (10.2%) were women, 273 (89.8%) were men and mean age was 60.59 +/-
      10.73. Analysis by the Kaplan-Meier method revealed that median survival was 6.0
      +/- 0.5 (95% CI: 5.1-6.9) months and 12 and 24-month survival rates were 25.27 +/
      2.99% and 11.48 +/- 2.77% respectively. By univariate analysis of 33 parameters,
      12 of them were found to be effective on survival and this relationship was
      statistically significant (p< 0.05). These parameters indicating poor prognosis
      were age > 70, ECOG performance score > 1, dyspnea, peripheral lymphadenomegaly
      (LAM), mediastinal invasion, pleural effusion, distant metastasis, elevated serum
      LDH, CA 19.9, CA-125 values, not receiving curative radiotherapy (RT) (> 50 Gy)
      or chemotherapy (CT). A multivariate analysis by Cox regression method revealed
      that advanced age, mediastinal invasion and metastatic disease were not
      independent prognostic factors on survival whereas ECOG performance score > 1 (p=
      0.000), absence of CT (p= 0.000) and curative RT (p= 0.018), dyspnea (p= 0.035),
      peripheral LAM (p= 0.022) and pleural effusion (p= 0.043) were independent
      prognostic factors on survival.

PMID- 15558355
TI  - [The pathogens and their antibiotic sensitivities in hospital-acquired pneumonia
      cases].
AB  - Dynamic precautions in the early diagnosis and treatment of hospital acquired
      pneumonias are necessary because of their high mortality. In these patients,
      invasive diagnostic approaches may be needed since clinical and radiological
      findings and other non-invasive approaches frequently fail to establish the
      diagnosis. Thirty eight patients were prospectively included in the study.
      Average age of patients was 45.5 +/- 16.4 years; 31 were males (81.6%) and 7
      (18.4%) were females. Pneumonia was detected in 9 (23.7%) cases during the first
      five days and in 29 (76.3%) cases after the fifth day of admission to the
      hospital. Bronchoscopic interventions diagnostic purpose were carried out in 25
      (65.8%) patients. The culture results were negative in 7 (18.4%) cases. While
      more than one pathogen was determined on the cultures of 16 (42.1%) patients only
      one pathogen was isolated in the cultures of 15 (39.4%) cases. The frequently
      isolated pathogen on cultures was Staphylococci (45.4%). Other pathogens were
      Enterobacter spp., Pseudomonas spp., Escherichia coli, Serratia and Streptococcus
      pneumoniae according to their frequency on cultures. High resistance rates to the
      third generation cephalosporins were determined. Eleven of 17 deaths in 38
      pneumonia cases were attributable to pneumonia. As a conclusion, isolation of
      pathogen and antibiotic resistance should be determined in the cases with
      hospital acquired pneumonia. Invasive diagnostic interventions were not avoided
      when necessary. Although pro-BAL and PSB methods were expensive, their use in
      selected cases may prevent unnecessary antibiotic use and contribute to a
      decrease in mortality rate.

PMID- 15558356
TI  - Plasma d-dimer levels increase with the severity of community acquired pneumonia.
AB  - The aim of this study is to investigate the relationship of the plasma D-Dimer (D
      d) level and the severity of the pneumonia in patients who have not any disease
      that may increase the D-d level, but pneumonia. This is prospective controlled
      study. Using the ATS 2001 Community Acquired Pneumonia (CAP) Guideline we divided
      the patients into two groups [severe (n= 14) and non-severe (n= 37) CAP] and
      looked for any significant difference in D-d levels with ELISA method among the
      patients groups and control group. Plasma D-d levels were 2438 +/- 2158 ng/mL in
      severe CAP group, 912.6 +/- 512.6 ng/mL in non-severe CAP group and 387 +/- 99.56
      ng/mL in the control group. Patients with non-severe CAP and those with severe
      CAP group both showed an increase in plasma levels of D-d compared to control
      group (p< 0.05, p< 0.001, respectively). We also found that the severe CAP group
      had increased in plasma levels of D-d compared to the non-severe CAP group (p<
      0.001). Plasma D-d level increases significantly in patients with CAP compared to
      control group. Plasma D-d levels increases significantly with the severity of the
      CAP.

PMID- 15558357
TI  - A questionnaire survey among Turkish physicians about sleep disorders.
AB  - We aimed to assess the knowledge of Turkish physicians about sleep disorders and
      the attitude of the physicians towards sleep medicine. We prepared a 24-item
      questionnaire, 7 of the questions were about the attitudes of the physicians and
      17 of them were about the knowledge of the physicians. We applied the
      questionnaire in all university and educational hospitals in Ankara, which is the
      capital city and the second largest city of Turkey. Two-hundred-fifteen medical
      doctors from 5 different specialties accepted to answer the questionnaire, and
      168 (78%) of them completed the questionnaire. 47% of the physicians rated
      themselves as they had little knowledge about sleep disorders, and 45% as they
      had enough knowledge about sleep disorders, however, the overall score was not
      high. They answered only 45.3% of the questions correctly. In the light of this
      survey, we concluded that medical education on sleep disorders should be extended
      both in length and in content to improve the quality of sleep disorders medicine
      in Turkey.

PMID- 15558358
TI  - [Circulating adhesion molecules in patients with chronic obstructive pulmonary
      disease].
AB  - The place of adhesion molecules that have a role in the immigration of
      intravascular leukocytes to the tissue with inflammation in the pathogenesis of
      chronic obstructive pulmonary disease (COPD) is controversial. Our purpose in
      this study was to examine the levels of soluble intracellular adhesion molecule-1
      (sICAM-1) and Mac-1 (CD11b/CD18), lymphocyte function associated antigen-1 (LFA
      1) in both neutrophils and lymphocytes in stable patients with COPD and in the
      healthy control groups consisting of non-smokers, and in smokers without COPD and
      also to evaluate the relationship between the parameters related to the severity
      of the disease. Peripheral venous blood samples of all the individuals were
      collected, and levels of sICAM-1 was measured quantitatively with ELISA method.
      Flow cytometry was used for Mac-1 and LFA-1 levels. Twenty-four stable patients
      with COPD (group I), 13 smokers (group II) and 14 healthy non-smokers (group III)
      were included in this study. In the COPD group, 12 smokers patients were
      considered as group IA, and 12 patients with non-smokers and biomass exposure
      were considered as group IB. No statistically significant differences were seen
      in LFA-1 examined in peripheric blood (PB) neutrophils and lymphocytes and sICAM
      in groups I, II, and III. Mac-1 examined in PB neutrophils was found to be
      significantly lower in group I when compared to groups II and III, however no
      difference could be seen in smokers' group of II and the control group III. Mac-1
      examined in PB lymphocytes were found to be higher in group I according to group
      II, however no statistically significant difference was seen between group I and
      control group. No statistically significant differences were seen in all adhesion
      molecules levels in group IA and group IB. As a result; it was found that Mac-1
      levels in PB neutrophils were decreased with the developing of COPD and Mac-1
      levels in PB lymphocytes were decreased in smokers, however increased following
      the development of COPD. No differences existed in sICAM and LFA-1 levels
      dependent on smoking and/or COPD.

PMID- 15558359
TI  - [Therapeutic bronchoscopic treatment of postintubation tracheal stenosis: 5
      cases].
AB  - Benign airway obstruction is known as curable by therapeutic bronchoscopic
      methods. Compared by surgical therapies it is comfortable and has no risks for
      the patients. For five patients who applied our clinic after tracheostomy and
      endotracheal intubation stenosis we used therapeutic bronchoscopic methods;
      "laser-stenotic silicon stent". In two patients after vaporization of membranous
      stricture by Neodimum Yttrium Aliminum Pevroskite Laser (Nd-YAP laser) who were
      seen posttracheostomy and postentubation; stenotic stent was implanted
      mechanically and/or by means of baloon dilatation. Membranous stricture area was
      coagulated by Nd-YAP-laser in other three cases and anatomic airway diameter was
      achieved mechanically and by baloon dilatation. In the follow up period we
      applied stenotic silicon stent implantation after second laser resection in whom
      restenosis observed. In conclusion; patients who had stenotic silicon stent
      implantation and having no problems in the follow up this therapeutic method is
      found to be curative.

PMID- 15558360
TI  - Coexisting bronchial carcinoid tumor and pulmonary tuberculosis in the same lobe:
      a case report.
AB  - The synchronous occurrence of pulmonary tuberculosis and bronchial carcinoid
      tumor is unusual. Although pulmonary tuberculosis can coexist with all
      histological types of lung cancer, few coexisting cases of bronchial carcinoid
      tumor and pulmonary tuberculosis have been reported. We present coexistent
      bronchial carcinoid tumor and pulmonary tuberculosis in the same lobe. A 39-year
      old woman was admitted to our clinic with chest pain for two months. Chest
      radiograph showed consolidation in the right lower field. Computed tomography of
      the thorax demonstrated multiple mediastinal lymphadenopathies, infiltration and
      atelectasis in the right lower lobe. Fiberoptic bronchoscopy showed a mass lesion
      totally obstructing the proximal right lower lobe bronchus. The pathological
      diagnosis was typical carcinoid tumor. Right lower lobectomy with mediastinal
      lymph node dissection was performed. The pathological examination of resected
      material revealed coexistent tuberculosis and carcinoid tumor in the same lobe
      and mediastinal tuberculous lymphadenitis.

PMID- 15558361
TI  - Solitary adrenal metastasis in large cell carcinoma of lung.
AB  - Metastatic non-small cell lung cancer (NSCLC) has a poor prognosis. Adrenal
      metastasis (AM), in NSCLC, are present in 5-10% of patients at initial
      presentation. Several case reports have shown that operation of isolated AM
      results in longer survival time. We describe a 55 year-old man with diagnosis of
      NSCLC with operable lung tumor and solitary AM treated with combination of
      neoadjuvant chemotherapy followed by primary site and metastasis surgery. He was
      diagnosed on March 2002 and is still alive.

PMID- 15558362
TI  - [Distal phalanx metastasis in operated bronchial carcinoma].
AB  - A 54 years old man who admitted with thoracolomber pain and pain at left knee had
      history of left pneumonectomy four months ago for squamous cell lung carcinoma.
      At physical examination swelling and hotness at the left knee, swelling and
      redness of the distal phalanx of the right third finger were found. Distal
      phalanx was not observed at the X-ray which was taken for suspect of metastasis.
      Incision biopsy was performed from this lesion and microscopic findings of the
      material were evaluated as metastatic squamous cell carcinoma. Bone metastasis
      are seen frequently at bronchial carcinoma, but hand metastasis are seen in 0.2%
      of all cases. This case is represented because of the rare metastatic
      localisation of bronchial carcinoma.

PMID- 15558363
TI  - Idiopathic pulmonary haemosiderosis.
AB  - Twenty seven years old woman was admitted to our hospital with dyspnea, severe
      hemoptysis and iron deficiency anemia. The chest X-ray showed bilateral
      interstitial markings with homogenous infiltration at right costodiafragmatic
      sinus. The patient was investigated for all alveolar hemorrhagic syndromes. The
      diagnosis of idiopathic pulmonary haemosiderosis (IPH) was made by open lung
      biopsy. IPH usually presents in infancy or within the first decade of life and is
      unknown aetiology. It is most common between ages 1-17 and exceedingly rare in
      adults. Clinical presentation of IPH varies from an insidious onset with anemia,
      cough, dyspnea to a fulminant onset with recurrent acute hemoptysis. Histological
      confirmation with open lung biopsy is often necessary for definite diagnosis.

PMID- 15558364
TI  - [Asthma and cost of illness].
AB  - The basic aim of the activities concerning health is to implement the initiatives
      for people to attain the best health status and sustain it. That's why these
      initiatives have to be chosen from the ones that consume minimum resource and
      affect life quality and duration in most beneficial way. Asthma is one of the
      most prevalent chronic disorders. Asthma brings significant direct and indirect
      costs to societies. To decrease the burden of asthma, it is necessary to
      emphasize its effects related to morbidity, mortality and material losses.
      Therefore, countries should give priority to cost of illness studies.

PMID- 15558365
TI  - Challenges to studying and delivering care to special populations--the example of
      women veterans.

PMID- 15558366
TI  - Differential recovery of the electroretinogram, visually evoked cortical
      potential, and electrically evoked cortical potential following vitrectomy:
      implications for acute testing of an implanted retinal prosthesis.
AB  - To determine the extent to which electrophysiologic tests of the afferent visual
      pathway are affected by vitrectomy, the procedure was performed in 15 eyes of 11
      adult Dutch-belted rabbits. An electroretinogram (ERG), visually evoked cortical
      potential (VECP), and electrically evoked cortical potential (EECP) were obtained
      preoperatively and sequentially after surgery. For electrical stimulations,
      biphasic impulses were delivered to the retina. Post-vitrectomy declines of 49,
      25, and 41% from the median baseline amplitudes and increases of 13, 18, and 17%
      from the median baseline latency values were found for ERG, VECP, and EECP,
      respectively. At 90 min, 13 to 30% of eyes still had an amplitude more than 10%
      below baseline on at least one of the three tests, whereas 10 to 47% of eyes had
      an abnormal latency more than 10% above baseline on at least one of the three
      tests. Amplitudes were more likely than latencies to return to near baseline, but
      for eyes that remained subnormal, the decline was greater for amplitudes than
      latencies. Significant alterations in retinal function, manifested by declines in
      amplitudes and increases in latencies of the ERG, VECP, and EECP, persist in a
      large proportion of eyes up to 90 min post-vitrectomy.

PMID- 15558367
TI  - Comparison of manual and computer-automated procedures for tinnitus pitch
      matching.
AB  - Clinical assessment of tinnitus usually includes pitch-matching between the
      tinnitus and a pure tone. Although such testing is performed routinely, response
      reliability has not been demonstrated yet. The present study continues a series
      of studies designed to develop automated methodology for quantifying tinnitus
      perceptual characteristics. Three methods for tinnitus pitch-matching were
      performed in a group of 42 subjects. Two methods were computer-automated (Binary
      and Subject-Guided) and the third method was a traditional manual technique. Each
      method provided excellent response reliability for about half of the subjects.
      The most reliable subjects, however, differed widely between the different
      methods. Each subject provided a total of 14 pitch matches using the three
      different methods. Analyses based on each subject's total of 14 pitch matches
      revealed the range of pitch matches for each subject. About half of the subjects
      selected pitch matches over a range of 2 1/3 octaves. Results of this study
      suggest that specifying the range of tinnitus pitch matches rather than
      attempting to identify a single pitch match may be more appropriate.

PMID- 15558368
TI  - A comparison of four electrical stimulation types on Staphylococcus aureus growth
      in vitro.
AB  - We evaluated the efficacy of common electrical stimulation (ES) types on
      bacterial growth in vitro using clinically relevant conditions. Four types of ES-
      continuous microamperage direct current (microADC), high-voltage pulsed current
      (HVPC), low-voltage monophasic milliamperage pulsed current (LVMmAPC), and low
      voltage biphasic milliamperage pulsed current (LVBmAPC)--were each applied to a
      separate set of culture plates containing Staphylococcus aureus for 1 h at 37
      degrees C on 3 consecutive days. After ES treatment, the zone of inhibition
      surrounding each electrode was measured. Zone of inhibition measurements showed a
      significant inhibitory effect for continuous microADC and HVPC (p < 0.05), but
      not for LVMmAPC and LVBmAPC. Differences in bacterial growth inhibition were not
      found for polarity and time. These data suggest that for infected wounds, HVPC
      and continuous microADC treatments may have an initial bacterial inhibitory
      effect, which does not significantly change with subsequent treatments.

PMID- 15558369
TI  - A comparative study of the effects of electrical stimulation and laser treatment
      on experimental wound healing in rats.
AB  - We investigated the effects of electrical stimulation (ES) and laser treatment on
      wound healing in rats. A randomized-controlled trial, conducted at the
      Experimental and Clinical Research Centre of Erciyes University (Kayseri,
      Turkey), divided 124 healthy female Swiss-Albino rats into four groups. A 6 cm
      linear incision was made at the dorsal skin of all rats. Group 1 was given a
      constant direct current of 300 microA for 30 min per day. The current was applied
      in negative polarity for the first 3 days and in positive polarity for the next 7
      days. Group 3 received a full-contact, continuous gallium-arsenide (GaAs) laser
      therapy, with a wavelength of 904 nm, an energy density of 1 J/cm2, and an
      average power of 6 mW for 10 min per day. The remaining two groups (Groups 2 and
      4) were considered the control groups and received sham treatment. All groups
      were treated for 10 days. Histopathologic and biochemical evaluations were
      conducted on 10 rats from each group on the 4th and 10th days, and wound breaking
      strength was measured for biomechanical evaluation on the 25th day of the study.
      Both ES and laser treatment proved significantly effective in the inflammatory
      phase compared with control groups (p < 0.05); however, the ES was even more
      effective than laser treatment, with more significant results (p < 0.05). In the
      proliferation and maturation phases, while ES and laser treatment were both found
      to be significantly effective treatment methods compared with the control groups,
      no statistically significant difference was observed between the two treatment
      groups (p > 0.05). Although ES and laser treatment both were effective in the
      maturation phase, increasing wound breaking strength compared with their control
      groups (p < 0.05), there was no statistically significant difference between the
      two treatment groups (p > 0.05). We conclude that ES and laser treatment both
      have beneficial effects during the inflammatory, proliferation, and maturation
      phases of a wound. Both ES and laser treatment can be used successfully in
      decubitis ulcers and chronic wounds, in combination with conventional therapies
      such as daily care and debridement of wounds; however, ES has more beneficial
      effects during the inflammatory phase in some parameters than laser treatment.

PMID- 15558370
TI  - Unresolved legal and ethical issues in research of adults with severe traumatic
      brain injury: analysis of an ongoing protocol.
AB  - This paper synthesizes federal and state laws and bioethics literature with
      observations from an ongoing research protocol to identify, define, and clarify
      the unresolved legal and ethical issues regarding research involving adults with
      traumatic brain injury (TBI). Solutions that protect rights and minimize
      unnecessary impediments to valuable clinical and scientific inquiry are also
      illustrated using the same protocol. Research was performed at intensive care,
      inpatient rehabilitation, and long-term acute chronic hospitals. Our research
      protocol identified five areas of law impacting adults with TBI: advanced
      directives, healthcare surrogacy acts, probate acts, power of attorney acts, and
      the Health Insurance Portability and Accountability Act. The published bioethics
      literature and responses from local human subject institutional review boards
      (IRBs) suggest that some of the unresolved ethical issues in research include
      defining vulnerability, defining informed voluntary consent, determining
      competency and/or decision-making capacity, using caregivers as subjects, and
      conducting multisite cooperative studies. Collaboration with IRB members and
      administrators as well as legal and research ethic scholars developed procedures
      that protect rights while avoiding unnecessary impediments to research.
      Investigations of persons with TBI and other cognitive impairments are governed
      by complicated and inconsistent regulations within the Common Rule and federal
      and state statues. A need for clear and consistent regulatory guidance regarding
      multisite studies of TBI persists. In lieu of regulatory guidance, carefully
      researched solutions for critical peer review are needed to guide future
      multisite investigations of TBI.

PMID- 15558371
TI  - Testing of elastomeric liners used in limb prosthetics: classification of 15
      products by mechanical performance.
AB  - The mechanical properties of 15 elastomeric liner products used in limb
      prosthetics were evaluated under compressive, frictional, shear, and tensile
      loading conditions. All testing was conducted at load levels comparable to
      interface stress measurements reported on transtibial amputee subjects. For each
      test configuration, materials were classified into four groups based on the
      shapes of their response curves. For the 15 liners tested, there were 10 unique
      classification sets, indicating a wide range of unique materials. In general,
      silicone gel liners classified within the same groups thus were quite similar to
      each other. They were of lower compressive, shear, and tensile stiffness than the
      silicone elastomer products, consistent with their lightly cross-linked, high
      fluid content structures. Silicone elastomer products better spanned the response
      groups than the gel liners, demonstrating a wide range of compressive, shear, and
      tensile stiffness values. Against a skin-like material, a urethane liner had the
      highest coefficient of friction of any liner tested, although coefficients of
      friction values for most of the materials were higher than interface
      shear:pressure ratios measured on amputee subjects using Pelite liners. The
      elastomeric liner material property data and response groupings provided here can
      potentially be useful to prosthetic fitting by providing quantitative information
      on similarities and differences among products.

PMID- 15558372
TI  - Load-shifting brace treatment for osteoarthritis of the knee: a minimum 2 1/2
      year follow-up study.
AB  - Objectives in treating primarily unicompartmental knee arthritis with a load
      shifting brace are pain relief, compliance, brace durability, and complication
      free treatment over multiple years. This was a single institution retrospective
      chart review, radiograph review, and telephone survey of patients treated from
      1997 to 1999 with a load-shifting knee brace. Forty-six patients (49 knees) with
      a minimum 2 1/2-year follow-up (average 3.3 years) were reviewed. Kaplan-Meier
      survivorship analysis revealed that load-shifting brace use had a survival of 76%
      at 1 year, 69% at 2 years, and 61% at 3 years. Younger patients had a higher
      likelihood of longer brace use than older patients. One patient had ipsilateral
      leg swelling and a pulmonary embolus after initiating bracing. Eliminating the
      high numbers of early failures would be desirable. One should be aware of the
      potential complication of venous thrombosis and thromboembolism.

PMID- 15558373
TI  - Comparison of the Easy Strutter Functional Orthosis System and axillary crutches
      during modified 3-point gait.
AB  - The Easy Strutter Functional Orthosis System (ESFOS) was designed to improve
      assistive device ambulatory efficiency. This crossover design study compared the
      ESFOS to axillary crutches during modified 3-point gait. Thirty-eight subjects
      (40-65 years of age) at > 1 year after unilateral total knee or hip replacement
      participated in this study. Heart rate, mean peak palmar and plantar force
      magnitude, and onset timing were monitored during self-directed pace ambulation.
      Between trials, subjects responded to questions on perceived exertion,
      stability/security, and comfort. One-way analyses of variance were used to
      evaluate condition differences for ratio or interval data (p < or = 0.01).
      Statistically significant differences were noted for mean peak palmar forces
      (reduced 45% and delayed 31%), mean peak plantar force onsets (delayed 30%), and
      energy expenditure index (EEI) (reduced 25%). Wilcoxon signed rank tests were
      used to evaluate condition differences for ordinal data. Subjects preferred the
      ESFOS to axillary crutches for comfort and security/stability on flat surfaces
      and stairs (p < or = 0.001). Results suggest greater ambulatory gait efficiency
      during ESFOS use. Further study is indicated with other patient populations.

PMID- 15558374
TI  - Computational method to evaluate ankle postural stiffness with ground reaction
      forces.
AB  - We examined an existing method for evaluating postural sway based on force-plate
      technology. Through an improved mathematical model of postural dynamics, we
      propose a new method, which better evaluated postural sway and, in addition,
      computed ankle moment and ankle postural stiffness directly from the measured
      ground reaction forces. An example is detailed that demonstrates the utility of
      this approach. The proposed method does not involve filtering or numerical
      integration and considers the platform inclination. Results from normal subjects
      show a linear relation between the ankle moment and the sway angle during quiet
      standing.

PMID- 15558375
TI  - Identification of key pinch forces required to complete functional tasks.
AB  - Reconstructive hand surgeries restore key pinch to individuals with pinch force
      deficits caused by tetraplegia. Data that define the magnitudes of force
      necessary to complete functional key pinch tasks are limited. This study aims to
      establish target pinch forces for completing selected tasks that represent a
      range of useful functional activities. A robot arm instrumented with a force
      sensor completed the tasks and simultaneously measured the forces applied to the
      task objects. Lateral pinch force requirements were calculated from these
      measured object forces. Pinch force requirements ranged from 1.4 N to push a
      button on a remote to 31.4 N to insert a plug into an outlet. Of the tasks
      studied, 9 of 12 required less than 10.5 N. These pinch force requirements, when
      compared to pinch forces produced by 14 individuals with spinal cord injuries
      (with and without surgical reconstruction of pinch), accurately predicted success
      or failure in 81% of subject trials. The prediction errors indicate a need to
      measure other factors such as pinch opening, force location, force direction, and
      proximal joint control.

PMID- 15558376
TI  - Attributional style and symptoms as predictors of social function in
      schizophrenia.
AB  - While the attributions of people with schizophrenia have been hypothesized to
      play a role in determining social behavior, contradictory predictions can be made
      about exactly what type of attributions contribute to social dysfunction. One
      possibility is that attributing undesirable events to internal, stable, and
      global factors might lead to poorer social function. An alternate possibility is
      that attributing events in general to internal, stable, and global factors might
      lead to better social function. As a test of these hypotheses, 40 participants in
      a post-acute phase of schizophrenia were administered the Attributional Style
      Questionnaire, the Positive and Negative Syndrome Scale, and the Quality of Life
      Scale. Stepwise multiple regressions controlling for age and education indicated
      that a lack of negative symptoms and the tendency to make stable attributions for
      life events in general predicted more frequent social contacts, a higher quality
      of social interaction, and better community participation on the Quality of Life
      Scale. Results suggest that the tendency to see life events as the result of
      unstable or unpredictable causes is associated with social dysfunction
      independent of symptom level.

PMID- 15558377
TI  - Use of Rasch person-item map in exploratory data analysis: a clinical
      perspective.
AB  - The National Institutes of Health (NIH) includes visual impairment in the 10 most
      prevalent causes of disability in America. As rehabilitation programs have the
      potential to restore independence and improve the quality of life for affected
      persons, NIH research priorities include evaluating their effectiveness. This
      paper demonstrates a clinical perspective on the use of the Rasch person-item map
      to evaluate the range and precision of a new vision function questionnaire in
      early analysis (prior to full sample). A self-report questionnaire was developed
      to measure the difficulty that persons with different levels of vision loss have
      performing daily activities. This 48-item Veterans Affairs Low-Vision Visual
      Functioning Questionnaire (VA LV VFQ-48) was administered to 117 low-vision
      patients. Preliminary analysis indicates that the questionnaire items are
      applicable to persons of differing abilities. The Rasch person-item map
      demonstrates that the field-test version of the VA LV VFQ-48 has good range and
      is well centered with respect to the person measure distribution. Construct
      validity and reliability are also demonstrated.

PMID- 15558378
TI  - Access denied: consequences of federal policy on seating and wheeled mobility.

PMID- 15558379
TI  - Recent QUERI workshop analyzes optimum treatment for combat amputees.

PMID- 15558380
TI  - Cerebral and cerebellar sensorimotor plasticity following motor imagery-based
      mental practice of a sequential movement.
AB  - Motor behavior and sensorimotor activation of the cerebrum and cerebellum were
      measured before and after motor imagery-based mental practice (MP) and physical
      practice (PP) of a sequential motor task. Two-button-press sequences (A, B) were
      performed outside a magnetic resonance imaging scanner and at 2 Hz inside the
      scanner during a pretest. Participants (n = 39) completed PP, MP, or no practice
      (NP) of Sequence A for 1 week and were posttested. Sequence A performance
      improved 121%, 86%, and 4% for the PP, MP, and NP groups, respectively (p <
      0.05), while Sequence B improved 56%, 40%, and 38% (p > 0.05). PP improvements
      were accompanied by increased striatal and decreased cerebellar activation, while
      MP improvements were accompanied by increased cerebellar, premotor, and striatal
      activation. The efficacy of MP for activating cerebral and cerebellar
      sensorimotor networks suggests that MP might be an effective substitute or
      complement to PP to activate compensatory networks for motor rehabilitation.

PMID- 15558381
TI  - Donepezil as an adjuvant to constraint-induced therapy for upper-limb dysfunction
      after stroke: an exploratory randomized clinical trial.
AB  - Donepezil, a primarily central acetylcholinesterase inhibitor, could potentiate
      learning in subjects with stroke by amplifying cholinergic input to the cerebral
      cortex from the nucleus basalis of Meynert. We tested this possible adjuvant
      effect of donepezil in a prospective randomized, double-blind, placebo
      controlled, parallel-group study of 20 subjects 1 or more years following stroke
      undergoing constraint-induced therapy (CIT) for upper-limb dysfunction. CIT had
      substantial and significant effects on both primary outcome measures, the Wolf
      Motor Function Test (WMFT) and the Motor Activity Log (amount), and all secondary
      measures, including the Box and Block Test, the Actual Amount of Use Test, the
      Fugl-Meyer Motor Scale-Upper Extremity, and the Caregiver Strain Index. Subjects
      receiving donepezil achieved differential gains on the WMFT approaching
      statistical significance (p = 0.067, corrected for multiple comparisons), but not
      on other measures. This study is inconclusive, but a larger randomized controlled
      trial with adequate statistical power should be pursued because of the potential
      benefits of the treatment to stroke survivors.

PMID- 15558382
TI  - Heel-region properties of prosthetic feet and shoes.
AB  - The properties of the prosthetic components prescribed to amputees have the
      potential to ameliorate or exacerbate their comfort, mobility, and health. To
      measure the difference in heel-region structural properties of currently
      available prosthetic feet and shoes, we simulated the period of initial heel
      ground contact with a pendulum apparatus. The energy dissipation capacity of the
      various prosthetic feet ranged from 33.6% to 52.6% of the input energy. Donning a
      shoe had a large effect. Energy dissipation of a Seattle Lightfoot 2 prosthetic
      foot was 45.3%, while addition of a walking, running, and orthopedic shoe
      increased energy dissipation to 63.0%, 73.0%, and 82.4%, respectively. The force
      versus deformation response to impact was modeled as a hardening spring in
      parallel with a position-dependent damping element. A nonlinear least-squares
      curve fit produced model coefficients useful for predicting the heel-region
      impact response of both prosthetic feet and shoes.

PMID- 15558383
TI  - Effects of shoe heel height on biologic rollover characteristics during walking.
AB  - This study investigated the effects of shoe heel height on the rollover
      characteristics of the biologic ankle-foot system. Ten nondisabled adult female
      volunteers walked using three pairs of shoes with varying heel heights and at
      three walking speeds with each pair of shoes. Kinematic and kinetic data needed
      to calculate the rollover shapes of the ankle-foot systems of the participants
      were collected. Rollover shapes are the effective rocker geometries that ankle
      foot systems conform to between heel contact and opposite heel contact.
      Parameters of the best-fit circular arcs to the rollover shapes were used in an
      examination of the effects of shoe heel height on the ankle-foot system. The
      results support the notion that nondisabled humans automatically adapt their
      ankle-foot systems to accommodate a range of shoe heel heights, resulting in
      rollover shapes that do not change appreciably. Given physiologic constraints,
      this adaptation may not be possible for very high heels.

PMID- 15558384
TI  - A systematic literature review of the effect of different prosthetic components
      on human functioning with a lower-limb prosthesis.
AB  - A correct prosthetic prescription can be derived from adapting the functional
      benefits of a prosthesis to the functional needs of the prosthetic user. For
      adequate matching, the functional abilities of the amputees are of value, as well
      as the technical and functional aspects of the various prosthetic components. No
      clear clinical consensus seems to be given on the precise prescription criteria.
      To obtain information about different prosthetic components and daily functioning
      of amputees with a prosthesis, we performed a systematic literature search. The
      quality of the studies was assessed with the use of predetermined methodological
      criteria. Out of 356 potentially relevant studies, 40 studies eventually
      qualified for final methodological analysis and review. Four satisfied all the
      criteria and were classified as A-level studies, 26 as B-level, and 10 studies as
      C-level studies. Despite a huge amount of literature, our formal clinical
      knowledge had considerable gaps concerning the effects of different prosthetic
      components and their mechanical characteristics on human functioning with a lower
      limb prosthesis. Therefore, with regard to prosthetic guideline development, we
      must still largely rely on clinical consensus among experts. The integration of
      knowledge from research with the expert opinion of clinical professionals and the
      opinions and wishes of consumers can form a solid base for a procedure on
      guideline development for prosthetic prescription.

PMID- 15558385
TI  - Ambulatory activity in men with diabetes: relationship between self-reported and
      real-world performance-based measures.
AB  - The measurement of physical activity, especially walking activity, is important
      for many outcome studies. In many investigations, the Physical Activity scale of
      the short-form-36 (SF-36) health assessment questionnaire is used in lieu of an
      actual physical measurement of walking. This study determined the relationship
      between the SF-36 questionnaire and the Step Activity Monitor (SAM), a real-world
      performance-based tool that counts the actual number of steps taken during daily
      activities. We studied the physical activity of 57 men with diabetes using step
      count monitoring and the SF-36 questionnaire. The subjects averaged 3,293
      steps/day, but had a very wide range (111-11,654) and a large standard deviation
      (SD = 2,037). The correlations between total daily steps and the SF-36 Physical
      Component Summary score, and the Physical Function, Bodily Pain, and Vitality
      scales of the SF-36 were only fair (Pearson's r = 0.376, 0.488, 0.332, 0.380,
      respectively). The corresponding coefficients of determination range from only
      7.7% to 23.8%. Physical activity is a complex concept not completely represented
      by either the SF-36 or the step counts. The correlation between actual walking
      activity and the SF-36 is not as strong as many researchers believe. Caution
      should be exercised with the use of the SF-36 to specifically measure walking
      activity.

PMID- 15558386
TI  - Interlimb symmetry of traumatic unilateral transtibial amputees wearing two
      different prosthetic feet in the early rehabilitation stage.
AB  - This study evaluated the SACH and the Greissinger Plus prosthetic feet, in terms
      of the symmetry provided between the lower limbs, in the case of unilateral
      transtibial amputees 16.3 weeks from the time of limb fitting and 38.9 weeks from
      surgery. Sagittal plane gait analysis was carried out for nine right-limb
      traumatic amputees. In all examined cases, the spatial and temporal parameters
      measured were significantly improved. When the symmetry indexes of the same
      parameters calculated with three different methods were considered, significant
      improvement was observed for the hip and ankle ranges of motion and the stance
      phase period. However, no significant differences were found for the symmetry
      indexes of the knee range of motion, cadence, and walking speed. In addition, for
      most spatial parameters, the statistical significance varied considerably among
      the three methods used for the analysis of symmetry.

PMID- 15558387
TI  - Quantification of prosthetic outcomes: elastomeric gel liner with locking pin
      suspension versus polyethylene foam liner with neoprene sleeve suspension.
AB  - For this randomized crossover trial, we compared two common transtibial socket
      suspension systems: the Alpha liner with distal locking pin and the Pe-Lite liner
      with neoprene suspension sleeve. Our original hypotheses asserted that increased
      ambulatory activity, wear time, comfort, and satisfaction would be found with the
      elastomeric suspension system. Thirteen subjects completed the study. Following
      2.5-month accommodation to each condition, ambulatory activity was recorded
      (steps/minute for 2 weeks), and subjects completed three questionnaires specific
      to prosthesis use and pain: the Prosthesis Evaluation Questionnaire (PEQ), a
      Brief Pain Inventory (BPI) excerpt, and the Socket Comfort Score (SCS). Upon
      completion, subjects selected their favored system for continued use. Ten
      subjects preferred the Pe-Lite and three the Alpha. Subjects spent 82% more time
      wearing the Pe-Lite and took 83% more steps per day. Ambulatory intensity
      distribution did not differ between systems. No statistically significant
      differences were found in questionnaire results. Subject feedback for each system
      was both positive and negative.

PMID- 15558388
TI  - Reliability and validity of the Family Satisfaction Scale with survivors of
      traumatic brain injury.
AB  - For this study, we investigated the reliability and validity of the FSS (Family
      Satisfaction Scale) in survivors of traumatic brain injury (TBI). The FSS was
      administered during the 12- and 60-month follow-up interviews. Data analyses
      included Cronbach's Alpha to determine internal consistency and analysis of
      variance to determine the relationship of FSS total score to Life Satisfaction
      Index-A (LSI-A) total scores, marital status, living arrangement, and number of
      family contacts outside the home. Cronbach's Alphas were 0.94 (12 months, N =
      541) and 0.95 (60 months, N = 340). FSS total score and marital status were
      significantly related at both 12 months (F(3, 534) = 6.04, p < 0.001) and 60
      months postdischarge (F(3, 335) = 4.52, p < 0.005). FSS total scores are
      correlated with the number of family contacts (r(342) = 0.12, p < 0.03) and with
      LSI-A total scores (r(337) = 0.43, p < 0.001). The FSS has excellent internal
      consistency with survivors of TBI. We also demonstrated the evidence of
      convergent validity.

PMID- 15558389
TI  - Perceived exertion and rehabilitation with arm crank in elderly patients after
      total hip arthroplasty: a preliminary study.
AB  - This preliminary study examined, in a restricted randomized trial, the effects of
      a 6-week arm-crank rehabilitation training program in elderly osteoarthrosis
      patients after total hip arthroplasty, first on physiological and perceptual
      responses and second on physical function. Two groups of patients were studied: a
      training group (N = 7, mean age = 74.9 yr, standard deviation [SD] = 5.0 yr) who
      followed a training program in addition to traditional rehabilitation, and a
      control group who followed traditional rehabilitation only (N = 7 mean age = 75.4
      yr, SD = 5.1 yr). At the beginning of the training program, the heart rate and
      the perceived exertion were not significantly correlated during the exercise
      session. However, at the end of the training program, five patients had a
      significant heart rate/perceived exertion relationship (p < 0.05). Furthermore,
      positive effects of the arm-crank rehabilitation training program were observed
      on cardioventilatory and functional responses in the training group compared with
      the control group. These results suggest that after an habituation period, most
      of our elderly osteoarthrosis patients experienced physical sensations that were
      connected to physiological responses. Therefore, perceived exertion could be
      useful in these patients to regulate exercise intensity, especially at the end of
      and after the rehabilitation period.

PMID- 15558390
TI  - Is the Human Activity Profile a useful measure in people with knee
      osteoarthritis?
AB  - This study evaluated the usefulness of the Human Activity Profile (HAP) in people
      with knee osteoarthritis (OA). People with OA (N = 226) completed the HAP and a
      battery of pain and physical function measures. Healthy elderly controls (N = 33)
      also completed the HAP, and 20 OA participants underwent repeat testing 2 to 7
      days later. Test-retest reliability was excellent (intraclass correlation
      coefficients 0.96 and 0.95). The HAP was sensitive enough to detect differences
      in physical activity between people with (N = 33) and without OA (N = 33) (p <
      0.01). When OA individuals were classified as impaired, moderately active, or
      active based on HAP score, differences in pain and physical function were
      detected (p < 0.05). Correlations between HAP and commonly used pain and physical
      function measures were weak to moderate (r = 0.18-0.63, all p < 0.01), indicating
      that the HAP measures additional information not gained by other assessment
      tools. The HAP is a reliable measure, and it is sensitive enough to discriminate
      between people with and without knee OA, and within an OA cohort. The HAP appears
      to have greater applicability in osteoarthritic women than men.

PMID- 15558391
TI  - Conservative methods for reducing lateral translation postures of the head: a
      nonrandomized clinical control trial.
AB  - Fifty-one retrospective, consecutive patients were compared to twenty-six
      prospective volunteer controls in a nonrandomized clinical control trial. Both
      groups had chronic neck pain and lateral head translation posture. For treatment
      subjects, beginning and follow-up pain scales and anteroposterior (AP) cervical
      radiographs were obtained after 12.8 weeks of care (average of 37 visits), while
      the duration was a mean of 12 months for control subjects. Digitized radiographs
      were analyzed for Risser-Ferguson angles and a horizontal translation distance of
      C2 from a vertical line through T3. For treatment, patients received the Harrison
      mirror-image postural methods, which include mechanically assisted manipulation,
      opposite head posture exercise, and opposite head translation posture traction.
      While no significant differences were found in the control group subjects' pain
      scores and AP radiographic measurements, statistically significant improvements
      were observed in the treatment group subjects' pain scores and lateral
      translation displacements of C2 compared to T3 (pretrial score: 13.7 mm,
      posttrial score: 6.8 mm) and in angle measurements.

PMID- 15558392
TI  - The potential of virtual reality for rehabilitation.

PMID- 15558393
TI  - An examination of the mechanisms of exercise-induced change in psychological well
      being among people with spinal cord injury.
AB  - For individuals with a spinal cord injury (SCI), regular exercise training leads
      to significant improvements in pain, stress, and depression. The mechanisms by
      which exercise effects change in these variables are poorly understood. To
      address this issue, we examined the mediated effects of exercise on the
      psychological well-being of individuals with SCI according to the relationships
      described in the Chronic Pain Process Model. Twenty-one individuals with
      traumatic SCI either participated in a 9-month, twice-weekly exercise program (n
      = 11), or participated as nonexercising controls (n = 10). Measures of pain,
      stress, and depression were administered at the baseline and 3, 6, and 9 months
      into the intervention. Change in pain mediated exercise-induced change in stress,
      F(4,17) = 7.72, p < 0.01. Change in stress mediated exercise-induced change in
      depression, F(4,17) = 7.68, p < 0.01. With the identification of these factors as
      mediators of exercise-related changes in pain and well-being, exercise
      interventions can be designed that specifically target these mediators and
      possibly maximize intervention efficacy.

PMID- 15558394
TI  - Physical function in sedentary and exercising older veterans as compared to
      national norms.
AB  - We examined the associations between sedentary older veterans, those regularly
      involved in an outpatient exercise program and physical function. Sedentary and
      currently exercising older veterans performed a 30 s chair-stand test and 6 min
      walk test as part of an exercise program. Test results were then compared to
      national norms. The exercisers' test scores were not significantly different from
      the national averages. However, their mean 6 min walk score approached being
      significantly better than the national average (p = 0.095). The sedentary group's
      scores were significantly lower (p < or = 0.05) than the exercisers' scores and
      the national averages for both tests. In this cohort, older veterans who maintain
      a regular program of physical activity function at a level considered average or
      slightly above average compared to their age-matched peers, while sedentary
      veterans are significantly below average. Healthcare providers need to stress the
      importance of regular exercise to their older veteran patients.

PMID- 15558395
TI  - Effect of an exercise program on functional performance of institutionalized
      elderly.
AB  - This study determined the effectiveness of a 6-month program of regular exercises
      for the improvement of functional performance of the elderly living in a nursing
      home. The 40 subjects aged 60 to 99 who took part in this trial were assigned
      either to a comparative group or an exercise group. The following variables were
      measured: functional performance with the use of an obstacle course, a lower-limb
      function test, and a 6-minute walk test (gait velocity); isometric strength of
      the knee extensors; proprioception of the lower limbs; mental status through the
      Mini-Mental State Examination (MMSE); and depression symptoms with the use of the
      Geriatric Depression Scale (GDS). In the exercise group, 19 subjects completed
      the program and attended an average of 32 (68%) sessions. At the end of the
      trial, the exercise subjects showed significant performance improvement in
      quantitative and qualitative obstacle course scores, lower-limb function test,
      gait velocity test, knee extensors strength, and the GDS, while the nonexercise
      subjects showed significant decrease in qualitative obstacle course score, lower
      limb function, gait velocity, MMSE, and the GDS.

PMID- 15558396
TI  - Visual and hearing impairment in elderly patients hospitalized for rehabilitation
      following hip fracture.
AB  - In a prospective study, we assessed the prevalence and significance of visual and
      hearing impairment in 896 patients who were hospitalized for rehabilitation
      following hip fracture. Visual impairment was defined as visual acuity equal to
      worse than 6/60 in the better of the two eyes. Hearing impairment was defined as
      mean decibel level equal to or higher than 60 in the better of the two ears.
      Visual impairment was found in 210 patients (23.4%) and hearing impairment was
      found in 231 patients (25.8%). Simultaneous visual and hearing impairment was
      seen in 72 patients (8%). In univariate analysis, the absolute efficacy of
      rehabilitation was significantly lower in patients with visual impairment
      compared to those without (p = 0.00001) and in patients with hearing impairment
      compared to those without (p = 0.002). However, in multivariate analysis, visual,
      but not hearing, impairment was found to be independently associated with the
      absolute efficacy of rehabilitation (p = 0.001). In light of these results, we
      propose that in the first phase of rehabilitation, patients' visual acuity needs
      to be optimized.

PMID- 15558397
TI  - Biomechanical and clinical evaluation of a newly designed polycentric knee of
      transfemoral prosthesis.
AB  - We have designed a new polycentric knee adopting a hydraulic unit and an
      intelligent mechanism. The biomechanical parameters of this prototype, such as
      the stance duration, peak knee flexion angle in stance and swing, peak hip
      flexion angle, and peak hip extension moments were analyzed at three different
      cadences (88, 96, 104 steps/min) in three amputees, and then compared to those of
      polycentric hydraulic knees currently in use. The same parameters were also
      measured for 10 healthy volunteers and subsequently analyzed. In the prototype,
      almost all the values of the parameters showed no significant variety in
      individuals at the different cadences. The situation was the same with the
      healthy volunteers. However, the values of the parameter for the conventional
      knee varied significantly with the individual at the different cadences. The
      prototype may be of practical use, contributing to a stable walk even at
      different cadences.

PMID- 15558398
TI  - Shape and volume change in the transtibial residuum over the short term:
      preliminary investigation of six subjects.
AB  - A preliminary investigation was conducted to characterize the magnitude and
      distribution of volume change in transtibial residua at two time intervals: upon
      prosthesis removal and at 2 week intervals. Six adult male unilateral transtibial
      amputee subjects, between 0.75 and 40.0 years since amputation, were imaged 10
      times over a 35-minute interval with a custom residual limb optical scanner.
      Volume changes and shape changes over time were assessed. Measurements were
      repeated 2 weeks later. Volume increase on socket removal for the six subjects
      ranged from 2.4% to 10.9% (median 6.0% +/- standard deviation 3.6%). Rate of
      volume increase was highest immediately upon socket removal and decreased with
      time (five subjects). In four subjects, 95% of the volume increase was reached
      within 8 minutes. No consistent proximal-to-distal differences were detected in
      limb cross-sectional area change over time. Limb volume differences 2 weeks apart
      ranged from -2.0% to 12.6% (0.6% +/- 5.5%) and were less in magnitude than those
      within a session over the 35-minute interval (five subjects). Multiple mechanisms
      of fluid movement may be responsible for short-term volume changes, with
      different relative magnitudes and rates in different amputees.

PMID- 15558399
TI  - Questionnaire for Persons with a Transfemoral Amputation (Q-TFA): initial
      validity and reliability of a new outcome measure.
AB  - The Questionnaire for Persons with a Transfemoral Amputation (Q-TFA) is a new
      self-report measure developed for nonelderly transfemoral amputees using a socket
      or osseointegrated prosthesis to reflect use, mobility, problems, and global
      health, each in a separate score (0-100). This paper describes the initial
      measurement properties of the Q-TFA as completed by 156 persons with a
      transfemoral amputation using a socket prosthesis (67% male, 92% nonvascular
      cases, mean age 51 years). Criterion validity was determined by associations
      between scores of the Q-TFA and the Short-Form 36 (SF-36)-Item Health Survey.
      Reliability was assessed by retest (n = 48) and by determination of the internal
      consistency. Correlations between Q-TFA and SF-36-Item Health Survey scales
      matched hypothesized patterns. Intraclass correlations were between 0.89 and
      0.97, and measurement error ranged from 10 to 19 points. Cronbach's alpha
      revealed good internal consistency, with no values less than 0.7. This study
      shows that the Q-TFA, applied to persons using a transfemoral socket prosthesis,
      has adequate initial validity and reliability.

PMID- 15558400
TI  - A new hip-knee-ankle-foot sling: kinematic comparison with a traditional ankle
      foot orthosis.
AB  - In this study, we performed a kinematic analysis of a new, low-cost sling for the
      lower limb, compared to a common ankle-foot orthosis (AFO). Gait with no
      orthosis, with the AFO, and with the new sling was analyzed in one hemiplegic
      subject. Both the AFO and the sling reduced the mean angle and ROM (range of
      movement) of the ankle and the vertical displacement of the center of mass. The
      sling, but not the AFO, restored the normal sequence heel-strike, forefoot
      contact of the affected side. The sling, but not the AFO, reduced the affected
      limb stance and stride duration, increased stride length, and improved walking
      speed. In conclusion, the proposed sling for the lower limb equally improved the
      affected ankle kinematics in contrast to the traditional AFO, and it also
      improved some gait variables in this hemiplegic subject.

PMID- 15558401
TI  - Measures of postural stability.
AB  - Dynamic posturography has become an important tool for understanding standing
      balance in clinical settings. A key test in the NeuroCom International
      (Clackamas, Oregon) dynamic posturography system, the Sensory Organization Test
      (SOT), provides information about the integration of multiple components of
      balance. The SOT test leads to an outcome measure called the "equilibrium score"
      (ES), which reflects the overall coordination of the visual, proprioceptive, and
      vestibular systems for maintaining standing posture. Researchers, therapists, and
      physicians often use the ES from the SOT as a clinically relevant measure of
      standing balance. We discuss here the formula used for evaluating the ES and
      propose an additional measure of postural stability, called the Postural
      Stability Index (PSI), that accounts for shear force and individual
      anthropomorphic measures. We propose that this new measure provides a clinically
      important adjunct to the current SOT and can be calculated from data already
      collected by the NeuroCom forceplate during the SOT.

PMID- 15558402
TI  - Comparison of the effects of laser and ultrasound treatments on experimental
      wound healing in rats.
AB  - A randomized controlled study investigated the effects of ultrasound and laser
      treatments on wound healing in rats. The duration of the inflammatory phase
      decreased with both laser and ultrasound treatments; however, laser was more
      effective than ultrasound, with more significant results. The proliferation phase
      showed, for both treatments, an increase in the level of hydroxyproline and the
      number of fibroblasts, as well as stimulation of the collagen synthesis and the
      composition. Laser treatment was again more effective than ultrasound. The wound
      breaking strength was significantly higher with both treatments, and no
      statistically significant difference emerged between the laser and ultrasound
      groups, although laser treatment provided a much greater increase in the wound
      breaking strength than ultrasound. Both treatments have beneficial effects on the
      inflammatory, proliferation, and maturation phases of wound healing. Both can be
      used successfully for decubitis ulcers and chronic wounds, in conjunction with
      conventional therapies such as debridement and daily wound caring. However, laser
      treatment was more effective than ultrasound in the first two phases of wound
      healing.

PMID- 15558403
TI  - Is there a standard of care for eccentric viewing training?
AB  - A study was conducted to determine the current Department of Veterans Affairs
      (VA) standard of practice for eccentric viewing (EV) training. EV training is the
      process of teaching patients to realign the visual image away from a diseased
      foveal/macular region onto healthier retina. Optometrists and Visual Skills
      Instructors at all VA blind rehabilitation centers (BRCs) and VICTORS (vision
      impairment centers to optimize remaining sight) programs were asked to rate
      preference for EV prescription criteria, evaluation, and training techniques.
      Responses were received from 70% of BRCs and 67% of VICTORS. The respondents
      reported that all programs include EV training. The average minutes of training
      per patient varied from 20 minutes to nearly 24 hours, with instructors within a
      single center varying by as much as two orders of magnitude. Routinely, 82% of
      optometrists prescribe EV training, yet no consensus was found among these
      practitioners as to the criteria for selecting the best EV area. The results of
      this survey reveal an inconsistent standard of practice across VA centers and
      demonstrate the need for prospective studies of the efficacy, effectiveness, and
      cost-effectiveness of EV training.

PMID- 15558404
TI  - Usage, performance, and satisfaction outcomes for experienced users of automatic
      speech recognition.
AB  - This paper presents a variety of outcomes data from 24 experienced users of
      automatic speech recognition (ASR) as a means of computer access. To assess usage
      and satisfaction, we conducted an in-person survey interview. For those
      participants who had a choice of computer input methods, 48% reported using ASR
      for 25% or less of their computer tasks, while 37% used ASR for more than half of
      their computer tasks. Users' overall satisfaction with ASR was somewhat above
      neutral (averaging 63 out of 100), and the most important role for ASR was as a
      means of reducing upper-limb pain and fatigue. To measure user performance, we
      asked users to perform a series of word processing and operating system tasks
      with their ASR systems. For 18 of these users, performance without speech was
      also measured. The time for nontext tasks was significantly slower with speech (p
      < 0.05). The average rate for entering text was no different with or without
      speech. Text entry rate with speech varied widely, from 3 to 32 words per minute,
      as did recognition accuracy, from 72% to 94%. Users who had the best performance
      tended to be those who employed the best correction strategies while using ASR.

PMID- 15558405
TI  - [Sepsis -- a disease with many challenges].

PMID- 15558406
TI  - ["The intensive care simulator": a new teaching-concept to train severe sepsis
      management].
AB  - BACKGROUND AND OBJECTIVE: In addition to basic research and development of new
      therapeutic strategies, the education of health care professionals who manage
      sepsis patients is an important step to decrease the high mortality of severe
      sepsis. Patient simulators are increasingly used for teaching in anaesthesia. A
      training program in sepsis management was developed, using a full-scale
      anaesthesia simulator including the setting of a modern intensive care unit, and
      its results were evaluated by means of a questionnaire. METHODS: The simulator is
      controlled from a separate room using a controlling computer provided with
      physiological models and pharmacokinetic as well as pharmacodynamic patterns of
      substances commonly used in anaesthesia and intensive care. An important element
      of the training program is the subsequent debriefing with different modules,
      according to the individual deficits and needs of the participants detected
      during simulation. RESULTS: From September 2002 to July 2004 82 physicians
      participated in the training program. 4 weeks after the training 52 % of the
      participants stated that they had changed their treatment behaviour due to the
      training content. They assessed the interactive simulator workshop
      semiquantitatively on a scale from 1 ("absolutely correct") to 7 ("not correct at
      all") as follows: Sepsis simulation training (SST) improves identification
      (mean+/-SD) (2.3 +/- 1.3) and treatment (2.5 +/- 1.2) of patients with severe
      sepsis, and SST including true-life scenarios is more appropriate than
      traditional lectures (1.5 +/- 0.7). CONCLUSION: The presented SST could be an
      effective way to train intensive care specialists in severe sepsis management.

PMID- 15558407
TI  - [Monitoring of plasma disappearance rate of indocyanine green in a patient with
      necrotizing fasciitis and septic shock].
AB  - HISTORY AND ADMISSION FINDINGS: A 45-year old man with diabetes mellitus and
      arterial hypertension was transferred with fever of unknown origin, suspected
      diabetic angiopathy and sepsis. On admission the patient presented all signs of
      septic shock. Livid coloured injuries on his right hand and petechial bleeding in
      distal extremities were observed. INVESTIGATIONS: A different origin of sepsis
      was not found in transesophageal ultrasound cardiography and computed tomography
      of cranium, chest and abdomen. DIAGNOSIS, TREATMENT AND COURSE: Immediately after
      admission early goal-directed therapy was initiated. Apart from calculated
      antibiotic therapy intensive insulin therapy and hydrocortisone substitution was
      begun. The patient presented a multiple organ dysfunction syndrome. Plasma
      disappearance rate of indocyanine green (PDR (ICG)) on admission was 20,4 %/min
      (normal range > 18 %/min) and fell to 6,8 %/min within 12 hours, while central
      venous oxygen saturation remained normal. Despite therapy according to current
      guidelines for severe sepsis, the patient deteriorated. Surgical debridement was
      performed suspecting necrotizing fasciitis and application of recombinant human
      activated protein C (rhAPC) started. PDR (ICG) rapidly raised to normal values;
      the patient recovered and was discharged after 9 days. CONCLUSIONS: Monitoring of
      PDR (ICG) allows for improved bedside evaluation of liver perfusion of the
      critically ill and is not only able to predict prognosis but may help in decision
      making for supportive therapies.

PMID- 15558408
TI  - [Molecular mechanisms of microcirculatory failure].

PMID- 15558409
TI  - [The value of central venous O(2) saturation for assessment of tissue
      oxygenation].

PMID- 15558410
TI  - [Current aspects of volume therapy in circulatory failure].

PMID- 15558411
TI  - [Sepsis management -- antibiotic therapy].
AB  - Sepsis is one of the most frequent infectious problems at Intensive Care Units,
      and sepsis is associated with significant mortality. The latter could not be
      markedly reduced in the last years, despite a number of advances in the field of
      volume substitution, catecholamines, and endocrinologic therapy. The reason might
      be that important steps towards overcoming of sepsis are the surgical resection
      of infectious foci and an adequate antibiotic treatment. A critical role plays
      the growing resistance of pathogens against the common antibiotics. Since no
      major progress in the development of new antibiotics can be expected for the next
      years, sepsis treatment must be focused on prevention of infection, and on an
      optimised application of current antibiotic substances. The key factors are a
      broad and high dose initial treatment, a de-escalation strategy according to the
      clinical course, and -with exceptions- a limitation of treatment to 7 to 10 days.
      Rotation of antibiotics should be performed, if problems with resistances exist
      or no specialist for infectious diseases is available on the Intensive Care Unit.

PMID- 15558412
TI  - [Vasodilators in right heart failure -- pro].

PMID- 15558413
TI  - [Vasodilators in right heart failure -- contra].

PMID- 15558414
TI  - [Systemic and regional effects of vasoactive drugs].

PMID- 15558430
TI  - [The determination of the size of samples through statistical methods].

PMID- 15558432
TI  - [Socio-therapy--a chance seldom used].

PMID- 15558433
TI  - [On the early discharge of schizophrenic patients].

PMID- 15558436
TI  - [Case reports still a topic?!].

PMID- 15558437
TI  - [Skin-level gastrostomy -- long-term results from a prospective trial in gastric
      and jejunal application].
AB  - OBJECTIVE: The usefulness of skin-level gastrostomy tubes (button systems) for
      maintaining nutrition support after primary insertion of percutaneous endoscopic
      gastrostomy (PEG) is widely accepted. After first promising experiences with
      newly developed skin-level gastrostomy system (Freka-Button Gastrostomy) the
      safety and long-term stability of this new tube was not defined. MATERIAL AND
      METHODS: In a cohort study we prospectively evaluated from 2.1998 until 12.2001
      for ease of use, complications, time to failure and long-term follow-up of 61
      Freka button gastrostomies inserted in 50 patients (mean age 57.6 years, range 6 
      78 years, 44 men, 6 women). Mean time after primary PEG placement was 6.3 months
      (range 1 - 30 months). RESULTS: Correct application of all buttons (48 gastric, 2
      jejunal) was easy and fast (median time 11 minutes) to perform. In 56 % we used a
      new Seldinger guide wire technique to improve stomal passage. Within the first
      ten days and during long-term follow-up (median 248, range 2 - 593 days) no major
      complication was seen. 11 systems had to be replaced mainly due to balloon
      failure (median 352, range 186 - 593 days). The total observation time were
      15,128 days with a system failure rate of 0.26 per year. CONCLUSION: The Freka
      button systems provides an easy-to-use, safe, and feasible alternative for long
      term use of skin-level gastrostomy. First jejunal application of this new device
      was promising but needs further evaluation.

PMID- 15558438
TI  - Current practice in managing patients on anticoagulants and/or antiplatelet
      agents around the time of gastrointestinal endoscopy -- a nation-wide survey in
      Germany.
AB  - Anticoagulants and antiplatelet agents are widely used in the prophylaxis and
      management of thromboembolic and cardiovascular diseases. Gastrointestinal
      bleeding is a well-known complication of these agents. Modification of
      anticoagulant and antiplatelet therapy is often required in patients undergoing
      surgical procedures and specific recommendations for the perioperative period
      have been issued. Fewer data exist with regard to the use of these agents around
      the time of endoscopic procedures. A survey of the American Society for
      Gastrointestinal Endoscopy (ASGE), performed several years ago, showed a wide
      variation between endoscopists in the management of anticoagulants and
      antiplatelet agents in the periendoscopic period. Subsequently, guidelines have
      been proposed by the ASGE as well as the German Society for Gastroenterology
      (DGVS). The aim of this study was to investigate the current practices among
      German endoscopists regarding the use of these medications in patients undergoing
      endoscopic procedures and to assess their adherence to published guidelines. Our
      data demonstrate that, in spite of the dissemination of guidelines, there is
      still a wide variation in the periendoscopic management of patients who are at
      increased risk for bleeding due to anticoagulants, especially in patients taking
      antiplatelet agents.

PMID- 15558439
TI  - Regional differences in the manifestation of gastrointestinal motor disorders in
      type 1 diabetic patients with autonomic neuropathy.
AB  - OBJECTIVE: The aim of this work was to establish the prevalence and severity of
      different gastrointestinal symptoms and their relationships to esophageal,
      gastric and recto-anal motor disturbances by manometry in patients with Type 1
      diabetes mellitus and autonomic neuropathy. PATIENTS AND METHODS: Sixteen
      patients (mean age: 53.4 +/- 14.9 years) with long standing type 1 diabetes
      mellitus (mean diabetes duration: 22.1 +/- 14.7 years) and autonomic neuropathy
      (mean Ewing score: 5.73 +/- 2.34) were investigated. The gastrointestinal symptom
      scores were established by using the Talley dyspepsia questionnaire. The motor
      function of the digestive tract was tested in the esophagus, in the stomach, and
      in the ano-rectum by perfusion manometry. RESULTS: Manometric evaluation of the
      esophagus did not reveal significant abnormalities in the region of the upper
      sphincter in patients with diabetes mellitus. In contrast, diabetic patients had
      decreased peristaltic wave amplitude, prolonged duration, decreased wave
      propagation velocity, and increased number of simultaneous contractions in the
      esophageal body, and decreased lower esophageal sphincter pressures with
      prolonged relaxation compared to the age- and sex-matched controls. Symptom
      analysis showed correlations between reflux symptoms and LES relaxation times,
      and between dysphagia scores and esophageal body peristaltic wave duration,
      propagation velocity and the rate of simultaneous contractions. In the gastric
      antrum, frequent, and often severe, fasting motility disorders were observed,
      which had no correlation with dyspeptic symptoms. In the ano-rectal region the
      diabetic patients had a lower squeezing-resting pressure difference, and impaired
      fecal expulsive function. Motility disorders were simultaneously present at
      multiple parts of the gastrointestinal tract in 13/16 cases. CONCLUSIONS: In
      patients with type 1 diabetes mellitus and autonomic neuropathy gastrointestinal
      motility disorders were observed frequently, and in most of the cases
      simultaneously. While esophageal and ano-rectal symptoms correlated better with
      the manometric abnormalities, the lack of correlation between the impaired
      fasting gastric motility and dyspeptic symptoms shows that, on the basis of the
      clinical symptom analysis, the prevalence of such motor disorders could be
      underestimated. The early recognition of gastrointestinal motility disorders may
      be important for the better long-term management of patients with type 1 diabetes
      mellitus.

PMID- 15558440
TI  - [Sonographic controlled drainage of a fluid formation of the spleen in
      combination with pancreatitis].
AB  - With regard to acute or chronic pancreatitis various complications involving the
      spleen can occur, hematoma of the spleen being a rare complication. We describe
      the case of a patient in reduced general condition with elevated pancreatic
      enzymes and signs of inflammation. During multiple examinations, hematoma of the
      spleen, as well as hematomas close to the left adrenal gland and a larger
      hematoma close to the gastric wall were detected. In computed tomography and due
      to the laboratory parameters a pancreatitis was diagnosed. After CT-controlled
      puncture a communication between both formations was considered possible which
      was in retrospect CT-assisted not successful. Subsequently an ultrasound
      controlled drainage was performed, finally resulting in a restitutio ad integrum,
      thereby avoiding splenectomy. The described percutaneous puncture of a fluid
      formation in the splenic area represents a non-surgical option in the therapy of
      intrasplenic pancreatic fluid formations.

PMID- 15558441
TI  - [Symptomatic biliary stones at the lower end of the common duct following
      hepaticoduodenostomy].
AB  - A 66-year-old patient developed episodes of severe pain due to recurrent
      cholangitis and pancreatitis. 2 years prior to this referral the patient had
      undergone an end-to-side hepaticoduodenostomy and a cholecystectomy because of
      choledocholithiasis and obstructive jaundice. 20 years previously a Billroth II
      operation had been carried out for the treatment of ulcer disease. Since the
      hepaticoduodenostomy the patient has suffered from recurrent epigastric pain,
      nausea and postprandial vomiting. An oedematous pancreatitis following a
      recurrent chronic cholangitis was assumed. As the intrahepatic biliary ducts
      appeared to be normal on radiological studies and hepatobiliary scintigraphy
      showed a downright transit of the tracer, recurrent cholangitis appeared at first
      to be a rather unlikely explanation. However, follow-up MRI and MRCP showed large
      calculi at the lower end of the common duct, which was also enlarged up to 1 cm.
      For this reason an open duodenotomy with subsequent papillosphincterotomy and
      retrograde choledochoscopy was carried out. The diagnosis was confirmed hereby
      and all calculi were removed during the operation. Since then the patient has
      been free of symptoms and complaints. This case shows that remaining calculi at
      the lower end of the common bile duct can cause severe clinical problems.
      Therefore the bile ducts should be inspected endoscopically and stones removed
      prior to, or during the primary operation.

PMID- 15558442
TI  - [New concepts in ultrasound education in gastroenterology by simulator training].
AB  - Ultrasound is one of the most important imaging methods in medicine. However,
      ultrasound education is complicated by varying quantities and qualities of
      specific pathologies resulting from distinct patient collectives. Furthermore,
      under current clinical conditions ultrasound educators as well as trainees
      frequently lack the time necessary for a sufficient ultrasound education.
      Finally, current ultrasound education materials including "gold standard" images
      are not ideally suited for teaching scanning three-dimensional pathologies. In a
      direct cross over study we recently proved, that the ultrasound simulator we
      developed simulated the real patient examination reliably and reproducibly. By
      using this simulator as well in the classical beginner and advanced level courses
      as in focused courses of abdominal emergencies for instance, ultrasound trainees
      are able to practice scanning of well defined pathologies under realistic
      conditions, which has not been possible before. Furthermore, the ultrasound
      simulator is well suited for a structured ultrasound training in single hospitals
      as well as in continuous medical education. Finally, objective, standardized
      ultrasound quality control has become possible with the simulator.

PMID- 15558443
TI  - [Transcutaneous perianal ultrasound (PAUS) for the imaging of fistulas and
      abscesses in Crohn's disease].
AB  - Pelvic MRI and transanal ultrasound constitute the gold standard for the imaging
      of perianal inflammatory lesions in Crohn's disease. Perianal ultrasound (PAUS),
      however, is rarely considered in recent literature. In contrast to the
      established methods, perianal ultrasound represents an easy, cost-effective and
      at the same time sensitive method for the imaging of perianal abscesses and
      fistulas. This article illustrates the performance of perianal ultrasound and
      shows typical images of pathological findings such as abscesses and fistulas.
      PAUS is especially useful for acute diagnostics to rule out perianal abscesses
      and for follow-up evaluation of fistula treatment. For example, complications
      such as abscesses can be detected in a timely manner.

PMID- 15558444
TI  - [Interventional therapy for liver metastases].
AB  - Interventional radiology offers not only local but also loco-regional therapeutic
      concepts for the treatment of liver metastases. While the local concepts are
      employed as image-guided, interstitial techniques, a vascular access is ideal for
      the loco-regional distribution of anti-tumour drugs. In the present article
      interstitial employed ablation methods such as radiofrequency ablation, laser
      induced thermotherapy and CT-guided brachytherapy are evaluated on the basis of
      the available literature. The field of loco-regional vascular techniques
      contributes analyses of intra-arterial chemotherapy via minimally invasively
      implanted port systems as well as transarterial chemoembolization.

PMID- 15558447
TI  - [Consensus-recommendations for sirolimus in liver transplantation].
AB  - Sirolimus is an m-TOR inhibitor without renal side effects and potentially
      protects against the development of malignancy. Due to a higher incidence of
      complications in two trials and an official warning in the drug information, the
      use of Sirolimus in liver transplantation is limited. The participants of this
      consensus meeting had to analyse and evaluate the literature with respect to the
      potential role of Sirolimus in liver transplantation. This consensus statement
      follows the scheme normally employed for the presentation of guidelines including
      the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover,
      the consensus included the experience of the authors with respect to the handling
      of Sirolimus after liver transplantation.

PMID- 15558448
TI  - [Bartonelloses].
AB  - Bartonellae belong to less known causal agents of many human diseases. They are
      gram-negative bacteria growing slowly on culture media enriched with hemin or
      bovine serum. The genus Bartonella, which currently involves more than 15
      species, is present worldwide. Bartonellae live in natural foci in dependence on
      the occurrence of natural host (rodents, felines, canidae, human) and insect
      vector (flea, tick, louse). By reservoir animals they usually cause permanent
      intraerythrocytic bacteraemia without system inflammation symptoms. A classical
      example of a human disease is cat scratch disease (CSD) caused by Bartonella
      henselae and characterised by regional lymphagoitis and lymphadenitis. Increasing
      interest is being devoted to the ability of Bartonella sp. (e.i. B. quintana) to
      cause the opportune infections with diverse clinical manifestation: bacillary
      angiomatosis, specific liver and spleen vasculitis (peliosis hepatis, splenis),
      endocarditis and others. The issue of Bartonella infections is relatively new and
      its importance is still growing with increasing knowledge in this field.

PMID- 15558449
TI  - [Prevention of infectious complications of central venous catheters in children].
AB  - According to literary data the use of central venous catheters (CVC) is burdened
      with a significantly higher number of complications than a peripheral venous
      approach. The management of these complications is difficult and may increase the
      morbidity and even mortality of critically sick patients. This is why there is
      such emphasis on the prevention of these serious complications. Strict antiseptic
      procedures are an absolute must when handling such catheters. To prevent catheter
      sepsis, as well as any contamination and colonization of a central venous
      catheter, it is essential to insert such a catheter under aseptic conditions; it
      calls for handling in a sterile manner and the same applies to all tubing and
      other connecting systems and to the preparation of infusion liquids and drugs.
      Moreover, the site of insertion has to be correctly selected and the catheter
      left in place only for the absolutely necessary time. Most effective in the
      prevention of catheter infections are the so-called maximum barrier measures
      applied to the insertion of CVCs.

PMID- 15558450
TI  - [Determination of sensitivity of biofilm-positive forms of microorganisms to
      antibiotics].
AB  - Nosocomial infections caused by biofilm-positive microorganisms are a serious
      therapeutic problem. In the biofilm, microorganisms are protected against adverse
      effects of the external environment, including the action of antibiotics. It is
      well known that the values of minimum inhibitory concentrations (MIC) determined
      for planktonic forms do not correspond to the actual concentrations of
      antibiotics necessary for the eradication of bacteria in a biofilm. The purpose
      of the study was to propose a method of determining minimum biofilm inhibitory
      concentrations (MBIC) and minimum biofilm eradication concentrations (MBEC) and
      to compare these values with MIC values. Biofilm-positive strains of
      Staphylococcus epidermidis were cultured so as to form a biofilm layer on
      polystyrene pegs. The biofilm on the pegs was then exposed to the action of
      antibiotics and after 18 hours we determined the minimum biofilm inhibitory
      concentration (MBIC). The evaluation of minimum biofilm eradication
      concentrations was done colorimetrically from the metabolic activity of surviving
      cells. MBIC and MBEC values were many times higher than MIC values. We selected
      such a duration of the biofilms cultivation on the pegs of the plate, which
      ensured that the number of bacterial cells corresponded to standard MIC
      assessment. The MBEC values established in our study indicate that the currently
      used concentrations of tested antibiotics cannot be used in monotherapy for an
      efficacious eradication of a biofilm. The MBEC determination is a far more
      laborious and time-consuming method than the determination of MIC, but the use of
      plates with pegs facilitates the handling of biofilms. The advantage of our
      method is the possibility of standardization of the size of the inoculum and thus
      of the whole MBEC assessment.

PMID- 15558451
TI  - [Aminoglycoside resistance of Acinetobacter baumannii hospital strains in the
      Czech Republic].
AB  - OBJECTIVE: To investigate the nature of aminoglycoside resistance of clinically
      important multidrug-resistant (MDR) Acinetobacter baumannii strains from the
      Czech Republic. MATERIAL AND METHODS: Seventy MDR hospital strains from 1991-2001
      classified into pan-European clones I (n = 41) and II (n = 21) and a group of
      other MDR strains (n = 8) were studied. Fifteen other strains wild-type
      susceptible to aminoglycosides were used as controls. Susceptibility to
      aminoglycosides was determined by the disk diffusion and agar dilution tests. The
      presence of six genes encoding different aminoglycoside-modifying enzymes (AME)
      and of the adeB gene encoding a component of the AdeABC efflux pump was detected
      using PCR. RESULTS: MDR strains showed the following pattern of resistance to
      aminoglycosides: kanamycin (93 %; inhibition zone diameters < or =13 mm),
      gentamicin (87 %; MICs > or =16 mg/l), amikacin (47 %; MICs > or =64 mg/l),
      tobramycin (31 %; MICs > or = 16 mg/l) and netilmicin (17 %; MICs ? 32 mg/l).
      Forty-six (66 %) MDR strains had netilmicin MICs of 8-16 mg/l in contrast to 0.5
      1.0 mg/l found for control susceptible strains. The presence of at least one of
      the following AME genes was detected in 66 (94 %) MDR strains: aphA1 (n = 56),
      aacC1 (n = 52), aphA6 (n = 39) and aadB (n = 20). The presence of these genes and
      phenotypes of resistance to kanamycin, gentamicin, tobramycin and amikacin were
      in good agreement. The genes encoding netilmicin-modifying enzymes (aacC2, aacA4)
      were not detected in any strain. Fifty-six (80 %) MDR strains comprised two to
      four different AME genes in eight combinations. Clones I and II shared all of the
      genes studied (with the exception of aadB not detected in clone I). The gene adeB
      was found in all MDR strains and eight of 15 control susceptible strains.
      CONCLUSION: Clinically relevant aminoglycoside resistance of Czech A. baumannii
      strains is significantly associated with the genes encoding enzymatic
      modification of kanamycin, gentamicin, amikacin and tobramycin. These genes can
      spread horizontally and emerge in different combinations leading to high-level
      resistance to multiple aminoglycosides. The AdeABC pump is likely to play a role
      in the intermediate susceptibility to netilmicin but further study is needed in
      this regard.

PMID- 15558452
TI  - [CD38 antigen as a marker for immunological follow-up in HIV-positive patients].
AB  - BACKGROUND: HIV infection causes chronic activation of cytotoxic CD8+ T
      lymphocytes, which is partly responsible for the hallmark of the disease-
      progressive loss of CD4+ T-lymphocytes. The aim of this study was to evaluate an
      influence of HIV infection and long-term antiretroviral therapy (HAART) on
      expression of the activation molecules CD38 on CD8+ T-lymphocytes. METHODS: A
      group of 16 HIV-positive patients treated with HAART was followed for 12 months.
      Also, we examined 10 persons with a newly diagnosed HIV infection that were not
      treated with HAART. Expression of CD38 molecules on CD8+ T-lymphocytes was
      determined with five-parameter cytometric analysis using monoclonal antibodies as
      well as their mean fluorescence intensity (MFI). RESULTS: The percentage of
      CD8+/CD38+ T-lymphocytes in HIV-positive patients treated with HAART
      significantly decreased during the follow-up period from 46.1 I 3.7 to 35.2 I 3.8
      (p = 0,01). Furthermore, the percentage of these cells correlated negatively with
      the number of CD4+T-lymphocytes at the beginning and the end of the study (r = 
      0,679, p < 0.01; r = -0,51, p = 0,05, respectively). There was no correlation
      between these parameters in persons with newly diagnosed HIV infection. However,
      the percentage of CD8+/CD38+ T-lymphocytes in these patients was significantly
      higher than in persons treated with HAART (68.5 I 5.3 vs. 35.2 I 3.8, p < 0,01).
      CONCLUSIONS: Our findings support the importance of expression of CD38 antigen on
      CD8+ T-lymphocytes as a biological and clinical marker of HIV infection and
      indicate its usefulness for monitoring of the efficacy of HAART therapy.

PMID- 15558453
TI  - [Spondylodiscitis caused by a strain of Staphylococcus aureus, in vitro sensitive
      to penicillin].
AB  - The case history of a man referred to our department with the diagnosis of
      purulent meningitis; actually, he presented spondylodiscitis of the lumbar spine
      with the infection spreading into the spinal canal and the left psoas muscle. The
      disease was caused by a strain of Staphylococcus aureus, which in vitro was
      sensitive to penicillin. However, treatment with crystalline penicillin in
      combination with ciprofloxacin failed. The paper suggests a differential
      diagnosis permitting to distinguish a typical purulent meningitis and an abscess
      in the spinal canal. The authors also discuss the suitability of administering
      penicillin in staphylococcal sepsis caused by a sensitive strain. The authors do
      not recommend crystalline penicillin in the management of severe staphylococcal
      infections even in cases, where the isolated S. aureus strain is really sensitive
      to penicillin.

PMID- 15558454
TI  - [Inappropriate combinations of antiretroviral drugs].
AB  - At present 19 antiretroviral drugs are available, which offer together 969
      possible triple-combinations. Only a few combinations, mainly of nucleoside
      inhibitors of reverse transcriptase, are contraindicated due to undesirable
      interactions, which may negatively influence the treatment efficacy or increase
      toxicity. With raising number of antiretroviral drugs there must also be paid
      more attention to possible interactions of these drugs.

PMID- 15558460
TI  - The extracellular matrix in development and regeneration. An interview with
      Elizabeth D. Hay.

PMID- 15558461
TI  - A life in research on lens regeneration and transdifferentiation. An interview
      with Goro Eguchi.

PMID- 15558462
TI  - Evolving eyes.
AB  - Despite the incredible diversity among extant eyes, laws of physics constrain how
      light can be collected resulting in only eight known optical systems in animal
      eyes. Surprisingly, all animal eyes share a common molecular strategy using opsin
      for catching photons, but there are a diverse collection of mechanisms with
      proteins unrelated to each other used to focus light for vision. However, opsin
      is expressed in either one of two types of photoreceptor that differ
      fundamentally in their structure and tissue of origin. Taken together, this
      collection of observations strongly suggests that eyes have had multiple origins
      with remarkable convergence due to physics and molecular conservation of the
      opsin protein. Yet recent work has shown that a family of conserved genes are
      involved in eye formation despite substantial differences in their structure and
      origin, leading to a controversy over whether eyes evolved once or repeatedly. A
      likely resolution of this discussion is that particular genes and genetic
      programs have become associated with specific features needed for eyes and such
      suites of genes have been recruited as new eyes evolve. Since specific genes and
      their products are used repeatedly, it is somewhat difficult to conceptualize
      their causal relationships relative to evolutionary processes. However, detailed
      comparison of developmental programs may offer clues about multiple origins.

PMID- 15558463
TI  - Historical perspective on the development and evolution of eyes and
      photoreceptors.
AB  - The development and evolution of eyes is an "old problem" in biology, which
      required a special treatment in Charles Darwin's "Origin of the species" (1882)
      under the heading of "Difficulties of the theory". Darwin postulated a simple and
      imperfect eye, as a prototype, which can vary and evolve under natural selection
      into more complex and perfect eyes. Based upon morphological criteria and the
      different modes of development of the different kinds of eyes, neodarwinists have
      postulated that the various eye-types are polyphyletic in origin and that the
      eyes have evolved independently in the various animal phyla. Recent developmental
      genetic experiments and molecular phylogenetic analyses cast serious doubts on
      this interpretation and argue strongly for a monophyletic origin of the eyes from
      a Darwinian prototype and subsequent divergent, parallel and convergent evolution
      leading to the various eye-types.

PMID- 15558464
TI  - Cubozoan jellyfish: an Evo/Devo model for eyes and other sensory systems.
AB  - Cnidaria are the most basal phylum containing a well-developed visual system
      located on specialized sensory structures (rhopalia) with eyes and statocyts. We
      have been exploring the cubozoan jellyfish, Tripedalia cystophora. In addition to
      containing simple photoreceptive ocelli, each rhopalium in Tridedalia has a large
      and small complex, camera-type eye with a cellular lens containing three distinct
      families of crystallins which apparently serve non-lenticular functions. Thus,
      Tridpedalia recruited crystallins by a gene sharing strategy as have mollusks and
      vertebrates. Tripedalia has a single Pax gene, PaxB, which encodes a structural
      and functional Pax 2/5/8-like paired domain as well as an octapeptide and Pax6
      like homeodomain. PaxB binds to and activates Tripedalia crystallin promoters
      (especially J3-crystallin) and the Drosophila rhodopsin rh6 gene in transfection
      tests and induces ectopic eyes in Drosophila. In situ hybridization showed that
      PaxB and crystallin genes are expressed in the lens, retina and statocysts. We
      suggest from these results that an ancestral PaxB gene was a primordial gene in
      eye evolution and that eyes and ears (mechanoreceptors) may have had a common
      evolutionary origin. Thus, the numerous structural and molecular features of
      Tridpalia rhopalia indicate that ancient cubozoan jellyfish are fascinating
      models for evo/devo insights into eyes and other sensory systems.

PMID- 15558465
TI  - Blind cavefish and heat shock protein chaperones: a novel role for hsp90alpha in
      lens apoptosis.
AB  - Lens apoptosis plays a central role in cavefish eye degeneration. Heat shock
      proteins (hsps) can regulate apoptosis; therefore, we examined the relationship
      between constitutive hsp70 and hsp90 expression and lens apoptosis. The model
      system is Astyanax mexicanus, a teleost species consisting of an eyed surface
      dwelling (surface fish) form and numerous blind cave-dwelling (cavefish) forms.
      Optic primordia are formed in the cavefish embryo but they subsequently undergo
      lens apoptosis, arrest in development and degenerate. Astyanax hsp90 and hsp70
      DNAs were isolated to use as probes to compare gene expression during surface
      fish and cavefish development. Hsp90beta, which encodes one of two hsp90
      isoforms, was not expressed in the surface fish or cavefish lens, whereas hsp70
      was expressed in the lens of both forms, suggesting that neither is directly
      involved in lens apoptosis. In contrast, hsp90alpha, the other hsp90 isoform, was
      expressed in the cavefish but not the surface fish lens. Hsp90alpha expression
      peaked shortly before the beginning of lens apoptosis in three convergent
      cavefish populations, suggesting a close relationship with lens apoptosis. The
      absence of hsp90beta in the lens allowed us to use geldanamycin and radicicol,
      specific inhibitors of hsp90 chaperone function, to determine whether lens cell
      death requires hsp90alpha expression. Both inhibitors blocked TUNEL labeling in
      the cavefish lens, suggesting that hsp90alpha is required for apoptosis. In
      contrast to their effects on the lens, these inhibitors induced TUNEL labeling in
      the surface epidermis, presumably due to effects on hsp90beta function, implying
      that the two-hsp90 isoforms may have contrasting roles in cell survival. We
      conclude that hsp90alpha plays a novel role in lens apoptosis and cavefish eye
      degeneration.

PMID- 15558466
TI  - From embryonic induction to cell lineages: revisiting old problems for modern
      study.
AB  - A history of embryological studies of lens development and regeneration is
      sketched, paying special attention to the contribution of these studies to the
      conceptual aspect of embryology and later developmental biology. Emphasis is made
      on the fact that the interaction of different tissues during development, namely
      embryonic induction, was first discovered during studies of the lens and that the
      degree of the dependence of lens development on the inductive effect of the eye
      cup varies among different species. Studies along the line of comparative
      experimental embryology at the species level should be informative, in particular
      in combination with the recent trend of evo-devo studies. The processes of lens
      regeneration and in vitro transdifferentiation indicate the existence of multiple
      cell lineages with the potential of lens development in one animal. The
      occurrence of Wolffian lens regeneration in nature can be reconsidered from the
      new "eco-devo" viewpoint.

PMID- 15558467
TI  - Conservation and non-conservation of genetic pathways in eye specification.
AB  - In this review we highlight two genetic pathways important for eye morphogenesis
      that are partially conserved between flies and vertebrates. Initially we focus on
      the ey paradigm and establish which aspects of this genetic hierarchy are
      conserved in vertebrates. We discuss experiments that evaluate the non-linear
      relationship amongst the genes of the hierarchy with a concentration on
      vertebrate functional genetics. We specifically consider the Six genes and their
      relationship to sine oculis, as tremendous amounts of new data have emerged on
      this topic. Finally, we highlight similarities between Shh/Hh directed
      morphogenesis mediated by basic Helix-Loop-Helix factors in vertebrate retinal
      cell specification and in specification of fly photoreceptors.

PMID- 15558468
TI  - The little R cell that could.
AB  - Drosophila eye development provides an excellent model system to study the role
      of inter-cellular signaling in the specification of unique cell fates. Behavioral
      screens by Benzer and his colleagues led to the identification of a gene,
      Sevenless, a receptor tyrosine kinase (RTK) receptor, required for the
      specification of the UV sensitive R7 cell. Genetic analysis further showed that
      the Ras/Raf/MAPK pathway function downstream of Sevenless in the specification of
      R7 fate. Signaling mediated by another RTK, EGFR and Notch have also been shown
      to function in either an antagonistic or a synergistic manner in the
      specification of cell fate during eye development. In some instances, these
      pathways are linked in a sequential manner by the regulation of the expression of
      Notch ligand, Delta by EGFR, while in others, these pathways function in a
      combinatorial fashion on enhancer elements to control target gene expression. In
      this review, we highlight the elegant genetic strategies used by several
      laboratories in early elucidation of the Sevenless pathway which helped link the
      RTK receptor to the Ras/Raf/MAPK cascade and discuss how EGFR and Notch signaling
      pathways are used in a reiterative manner and by combining in different modes,
      generate sufficient diversity required for the specification of unique cell
      fates.

PMID- 15558469
TI  - Regulation of vertebrate eye development by Rx genes.
AB  - The paired-like homeobox-containing gene Rx has a critical role in the eye
      development of several vertebrate species including Xenopus, mouse, chicken,
      medaka, zebrafish and human. Rx is initially expressed in the anterior neural
      region of developing embryos, and later in the retina and ventral hypothalamus.
      Abnormal regulation or function of Rx results in severe abnormalities of eye
      formation. Overexpression of Rx in Xenopus and zebrafish embryos leads to
      overproliferation of retinal cells. A targeted elimination of Rx in mice results
      in a lack of eye formation. Mutations in Rx genes are the cause of the mouse
      mutation eyeless (ey1), the medaka temperature sensitive mutation eyeless (el)
      and the zebrafish mutation chokh. In humans, mutations in Rx lead to
      anophthalmia. All of these studies indicate that Rx genes are key factors in
      vertebrate eye formation. Because these results cannot be easily reconciled with
      the most popular dogmas of the field, we offer our interpretation of eye
      development and evolution.

PMID- 15558470
TI  - A re-examination of lens induction in chicken embryos: in vitro studies of early
      tissue interactions.
AB  - Early studies on lens induction suggested that the optic vesicle, the precursor
      of the retina, was the primary inducer of the lens; however, more recent
      experiments with amphibians establish an important role for earlier inductive
      interactions between anterior neural plate and adjacent presumptive lens ectoderm
      in lens formation. We report here experiments assessing key inductive
      interactions in chicken embryos to see if features of amphibian systems are
      conserved in birds. We first examined the issue of specification of head ectoderm
      for a lens fate. A large region of head ectoderm, in addition to the presumptive
      lens ectoderm, is specified for a lens fate before the time of neural tube
      closure, well before the optic vesicle first contacts the presumptive lens
      ectoderm. This positive lens response was observed in cultures grown in a wide
      range of culture media. We also tested whether the optic vesicle can induce
      lenses in recombinant cultures with ectoderm and find that, at least with the
      ectodermal tissues we examined, it generally cannot induce a lens response.
      Finally, we addressed how lens potential is suppressed in non-lens head ectoderm
      and show an inhibitory role for head mesenchyme. This mesenchyme is infiltrated
      by neural crest cells in most regions of the head. Taken together, these results
      suggest that, as in amphibians, the optic vesicle cannot be solely responsible
      for lens induction in chicken embryos; other tissue interactions must send early
      signals required for lens specification, while inhibitory interactions from
      mesenchyme suppress lens-forming ability outside of the lens area.

PMID- 15558471
TI  - Pathways regulating lens induction in the mouse.
AB  - For more than a century, the lens has provided a relatively simple structure in
      which to study developmental mechanisms. Lens induction, where adjacent tissues
      signal the cell fate changes that result in lens formation, have been of
      particular interest. Embryological manipulations advancing our understanding have
      included the Spemann optic rudiment ablation experiments, optic vesicle
      transplantations as well as more contemporary work employing lineage tracers. All
      this has revealed that lens induction signaling is a multi-stage process
      involving multiple tissue interactions. More recently, molecular genetic
      techniques have been applied to an analysis of lens induction. This has led to
      the identification of signaling pathways required for lens induction and early
      lens development. These include the bone morphogenetic protein (Bmp) signaling
      pathways where Bmp4 and Bmp7 have been implicated. Though no fibroblast growth
      factor (Fgf) ligand has been implicated at present, the Fgf signaling pathway
      clearly has an important role. A series of transcription factors involved in
      early lens development have also been identified. These include Pax6, the Meis
      transcription factors, Six3, Mab21l1, FoxE3, Prox1 and Sox2. Importantly,
      analysis has indicated how these elements of the lens induction pathway are
      related and has defined genetic models to describe the process. It is a future
      challenge to test existing genetic models and to extend them to incorporate the
      tissue interactions mediated by the molecules involved. Given the complexity of
      this and many other developmental processes, a second century of analysis will be
      welcome.

PMID- 15558472
TI  - Analysis of mouse eye development with chimeras and mosaics.
AB  - Analysis of experimental mouse chimeras (chimaeras) and mosaics provides a means
      of investigating patterning and differentiation within the developing mammalian
      eye. Chimeric and mosaic mice carry two or more genetically distinct cell
      populations and extend the repertoire of analytical tools available to the
      geneticist. Here we review the impact these techniques have had on our
      understanding of eye organogenesis. Chimeras and mosaics are routinely used to
      investigate cell lineages, patterns of growth and gene function, and provide a
      means to clear analytical hurdles that otherwise limit standard genetic
      approaches. In particular, chimeras are used to investigate the roles of genes in
      tissues that do not develop in conventional mutant or knock-out mice, to test
      whether genes act cell autonomously or non-autonomously in different tissues and
      to dissect tissue-tissue interactions in less tractable, complex systems.
      Chimeras, in which cells of different genetic composition are mixed at a fine
      scale cellular level, may provide qualitatively different data from mosaic mice
      with conditional knockouts. The uses of chimeras, Cre-loxP mosaics and in vitro
      tissue recombination for study of ocular organogenesis are compared. Wider use of
      mosaics and chimeras should provide further insights into eye development.

PMID- 15558473
TI  - Lens differentiation and crystallin regulation: a chick model.
AB  - The vertebrate lens is a transparent polarized tissue that acts as the gateway
      for vision. The chick lens is an excellent model for studying tissue
      organogenesis, since it is both accessible and easily manipulated during
      embryonic stages. The chick lens consists of two morphologically discrete
      compartments, the epithelium and the fiber-cell mass. Evidence indicates that the
      early phases of lens development involve several sequential events, including
      tissue interactions, cell proliferation and differentiation. The morphological
      change during lens development is associated with the concurrent and distinct
      functions of numerous transcription factors. Diffusible molecules from the
      complementary neural tissue play vital roles during the entire process of lens
      development. Lens tissue is characterized by the ample production of crystallins,
      lens specific proteins which provide structural integrity and functional
      properties to the lens. Thus, the study of crystallin regulation should provide
      insight into the development of a functional lens during embryogenesis. This
      process has been shown to involve a complex and evolutionary conserved pathway
      supported by different regulatory proteins.

PMID- 15558474
TI  - Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch
      mechanisms for cell differentiation.
AB  - When the cloning era arrived, our first target for cloning was the delta1
      crystallin gene of the chicken, the lens-specific gene expressed earliest
      following lens induction. We have investigated the regulation of this gene with
      the idea that the mechanism of its activation must reflect that of lens
      differentiation per se. We here summarize the investigation carried out in our
      group along this line over the past 20 years. The delta1-crystallin gene is
      regulated by an enhancer in the third intron, and the specificity of this
      regulation is governed by a DNA region (called DC5) of only 30 bp DNA bound by
      two transcription factors. These factors have been identified as SOX1/2/3 (Group
      B1 SOX proteins, SOX2 being the major player) and Pax6, and have been shown to
      bind cooperatively to DC5 and form a ternary complex having a robust potency for
      transcriptional activation. In the embryo, Pax6 is widely expressed in the head
      ectoderm before the lens is formed, and as the optic vesicle comes into contact
      with the ectoderm, SOX2/3 expression is induced in the contacted area of the
      ectoderm, thereby allowing Pax6 and SOX2/3 to meet in the same cell nucleus,
      where they can then activate a battery of genes for early lens development
      including delta1-crystallin. Thus, the cooperative action of Pax6 and SOX2
      initiates lens differentiation. More broadly, SOX1/2/3 interact with various
      partner transcription factors, and participate in defining distinct cell states
      that depend on the partner factors: Pax6 for lens differentiation, Oct3/4 for
      establishing the epiblast/ES cell state, and Brn2 for the neural primordia. Thus,
      the regulation of SOX2 (and SOX1/3) and its partner factors, exemplified by Pax6,
      determines the spatio-temporal order of the occurrence of cell differentiation.

PMID- 15558476
TI  - Contributions by members of the TGFbeta superfamily to lens development.
AB  - Members of the TGFbeta superfamily of growth and differentiation factors,
      including the TGFbeta, BMP, activin and nodal families, play important signaling
      roles throughout development. This paper summarizes some of the functions of
      these ligands in lens development. Targeted deletion of the genes encoding one of
      the BMP receptors, Alk3 (BMP receptor-1A), showed that signaling through this
      receptor is essential for normal lens development. Lenses lacking Alk3 were
      smaller than normal, with thin epithelial layers. The fiber cells of Alk3 null
      lenses became vacuolated and degenerated within the first week after birth.
      Lenses lacking Alk3 function were surrounded by abnormal mesenchymal cells,
      suggesting that the lenses provided inappropriate signals to surrounding tissues.
      Lens epithelial and fiber cells contained endosomes that were associated with
      activated (phosphorylated) SMAD1 and SMAD2. Endosomal localization of pSMAD1 was
      reduced in the absence of Alk3 signaling. The presence of pSMAD2 in lens fiber
      cell nuclei and the observation that the activin antagonist follistatin inhibited
      lens cell elongation suggested that an activin-like molecule participates in lens
      fiber cell differentiation. Lenses deficient in type II TGFbeta receptors were
      clear and had fiber cells of normal morphology. This suggests that TGFbeta
      signaling is not essential for the normal differentiation of lens fiber cells.
      The targeted deletion of single or multiple receptors of the TGFbeta superfamily
      in the lens should further characterize the role of these signaling molecules in
      lens development. This approach may also provide a useful way to define the
      downstream pathways that are activated by these receptors during the development
      of the lens and other tissues.

PMID- 15558477
TI  - Regulation of cell adhesion and migration in lens development.
AB  - Cell movements during lens development and differentiation involve dynamic
      regulation of cell-matrix and cell-cell adhesion. How these processes are
      regulated depends on the particular array of matrix components and adhesion
      proteins that are expressed, as well as the signaling pathways that affect them.
      This review examines what is known about adhesion proteins and their regulation
      in the lens in light of recent findings about the mechanism of cell migration.
      The characteristic shape and organization of the lens depends on highly regulated
      cell movements during development and differentiation. Epithelial cells at the
      equator migrate posteriorly, bringing them into contact with factors in the
      vitreous humor and initiating differentiation. Elongation of the differentiating
      fiber cells is coupled with directed migration, posteriorly along the capsule and
      anteriorly along the fiber cell-epithelial interface, to generate a symmetrically
      organized fiber cell mass with aligned suture planes. To make these movements,
      cells systematically create and dissolve cell-cell and cell-matrix adhesions,
      form connections between these adhesions and the cytoskeleton, and generate
      contractile force. Since errors in cell migration may lead to aberrant lens shape
      or misplacement of the lens sutures, precise regulation of each step is essential
      for the optical quality of the lens. Recent advances in cellular developmental
      biology have begun to shed light on the molecular mechanisms underlying cell
      movements and the changes in adhesion that make them possible. This review will
      summarize those findings and relate them to relevant studies of the lens to
      provide an outline of the cellular events that lead to lens morphogenesis.

PMID- 15558475
TI  - Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred
      expression of crystallins in lens.
AB  - Lens development is an excellent model for genetic and biochemical studies of
      embryonic induction, cell cycle regulation, cellular differentiation and signal
      transduction. Differentiation of lens is characterized by lens-preferred
      expression and accumulation of water-soluble proteins, crystallins. Crystallins
      are required for light transparency, refraction and maintenance of lens
      integrity. Here, we review mechanisms of lens-preferred expression of crystallin
      genes by employing synergism between developmentally regulated DNA-binding
      transcription factors: Pax6, c-Maf, MafA/L-Maf, MafB, NRL, Sox2, Sox1,
      RARbeta/RXRbeta, RORalpha, Prox1, Six3, gammaFBP-B and HSF2. These factors are
      differentially expressed in lens precursor cells, lens epithelium and primary and
      secondary lens fibers. They exert their function in combination with ubiquitously
      expressed factors (e.g. AP-1, CREB, pRb, TFIID and USF) and co
      activators/chromatin remodeling proteins (e.g. ASC-2 and CBP/p300). A special
      function belongs to Pax6, a paired domain and homeodomain-containing protein,
      which is essential for lens formation. Pax6 is expressed in lens progenitor cells
      before the onset of crystallin expression and it serves as an important
      regulatory factor required for expression of c-Maf, MafA/L-Maf, Six3, Prox1 and
      retinoic acid signaling both in lens precursor cells and the developing lens. The
      roles of these factors are illustrated by promoter studies of mouse alphaA-,
      alphaB-, gammaF- and guinea pig zeta-crystallins. Pax6 forms functional complexes
      with a number of transcription factors including the retinoblastoma protein, pRb,
      MafA, Mitf and Sox2. We present novel data showing that pRb antagonizes Pax6
      mediated activation of the alphaA-crystallin promoter likely by inhibiting
      binding of Pax6 to DNA.

PMID- 15558478
TI  - Expression of Frizzleds and secreted frizzled-related proteins (Sfrps) during
      mammalian lens development.
AB  - Recent studies indicate a role for Wnt signaling in regulating lens cell
      differentiation (Stump et al., 2003). Here we investigated expression patterns of
      Wnt receptors, the Frizzleds (Fzs) and the Wnt signaling regulators, the secreted
      frizzled-related proteins (Sfrps), during rodent lens development. RT-PCR showed
      that Fz receptors, Fz1-Fz8 are expressed in lens. In situ hybridization showed
      that all the Fz genes examined have similar expression patterns. Fzs are
      expressed throughout the early lens primordium. At embryonic day 14.5 (E14.5), Fz
      gene expression is predominantly localized to the epithelium and elongating cells
      at the lens equator. Fz expression is absent from lens fibers. This pattern of Fz
      gene expression continues throughout early postnatal development.
      Immunolocalization studies showed that Fz protein distribution closely follows
      that of the mRNAs. In addition, epithelial cells in FGF-treated explants show
      strongest Fz reactivity in cellular protrusions as they migrate and elongate.
      Sfrp1- Sfrp5 are expressed and all, except Sfrp2, have similar patterns of
      expression to each other and to the Fzs during lens development. Sfrp2 is
      strongly expressed in all lens pit cells but becomes restricted to the
      presumptive epithelial cells of the lens vesicle. By E14.5, Sfrp2 is only present
      in a few cells above the lens equator. Sfrp2 is not detected in the lens at E18.5
      or at later stages. This study shows that multiple Fz and Sfrp genes are
      expressed during lens morphogenesis and differentiation. This is consistent with
      a role for Wnt-Fz signaling during both embryonic and postnatal lens development.

PMID- 15558479
TI  - Activated Ras induces lens epithelial cell hyperplasia but not premature
      differentiation.
AB  - Growth factor signaling is implicated in the regulation of lens cell
      proliferation and differentiation during development. Activation of growth factor
      receptor tyrosine kinases is known to activate Ras proteins, small GTP-binding
      proteins that function as part of the signal transduction machinery. In the
      present study, we examined which classical Ras genes are expressed in lens cells
      during normal development and whether expression of an activated version of Ras
      is sufficient to induce either lens cell proliferation or fiber cell
      differentiation in transgenic mice. In situ hybridization showed H-Ras, K-Ras and
      N-Ras are ubiquitously expressed in all cells of the embryonic (E13.5) eye, with
      N-Ras showing the highest level of expression. The expression level of N-Ras
      decreases during later stages of embryonic development, and is nearly undetected
      in postnatal day 21 lenses. To generate transgenic mice, a constitutively active
      H-Ras mutant was linked to a chimeric regulatory element containing the mouse
      alphaA-crystallin promoter fused to the chick delta1-crystallin lens enhancer
      element. In the lenses of the transgenic mice, the transgene was expressed in
      both lens epithelial and fiber cells. Expression of activated Ras was sufficient
      to stimulate lens cell proliferation but not differentiation, implying that
      alternative or additional signal transduction pathways are required to induce
      fiber cell differentiation.

PMID- 15558480
TI  - Development of lens sutures.
AB  - Cylindrical map projections (CMPs) have been used for centuries as an effective
      means of plotting the features of a 3D spheroidal surfaces (e.g. the earth) on a
      2D rectangular map. We have used CMPs to plot primate fiber cell organization
      from selected growth shells as a function of growth, development and aging. Lens
      structural parameters and features were derived from slit-lamp, light and
      transmission and scanning electron micrographs. This information was then used to
      create CMPs of lenses that were then correlated with azimuthal map projections
      (AMPs; projections that are radially symmetric around a central point [the
      poles]) to reveal different suture patterns during distinct time periods. In this
      manner, both lens fiber and suture branch locations are defined by degrees of
      longitude and latitude. CMPs and AMPs confirm that throughout defined periods of
      development, growth and ageing, increasingly complex suture patterns are formed
      by the precise ordering of straight and opposite end curvature fibers. However,
      the manner in which additional suture branches are formed anteriorly and
      posteriorly is not identical. Anteriorly, new branches are added between extant
      branches. Posteriorly, pairs of new branches are formed that progressively
      overlay extant branches. The advantage of using CMPs is that the shape and
      organization of every fiber in a growth shell can be observed in a single image.
      Thus, the use of CMPs to plot primate fiber cell organization has revealed more
      complex aspects of fiber formation that may explain, at least in part, changes in
      lens optical quality as a function of age and pathology. In addition, more
      accurate measurements of fiber length will be possible by incorporating the
      latitudinal and longitudinal locations of fibers.

PMID- 15558481
TI  - Corneal development associated with eyelid opening.
AB  - The development of the cornea as a tissue initiates as early as five weeks in the
      human embryo. This development continues gradually until the time of eyelid
      opening, which is associated with major developmental changes. These events, most
      easily observed in rodents, which are born with closed eyelids, include
      alterations in the rate of cell proliferation in the epithelium, stroma and
      endothelium; differentiation of the epithelium; appearance of a tear film and
      tear-film-associated proteins; and swelling and thinning of the stroma. Eyelid
      opening is also associated with numerous alterations in gene expression. These
      events are the subject of this review. Readers are directed to the article by
      Wolosin et al., also in this volume, for an in-depth discussion of early corneal
      development.

PMID- 15558482
TI  - Genetic control of retinal specification and determination in Drosophila.
AB  - The Drosophila compound eye has long served as an outstanding model system to
      study many processes, including cell fate specification, cell division, cell
      growth and cell death. In addition, exploring the molecular basis of eye
      specification in Drosophila has identified a set of nuclear factors that trigger
      the conversion of a group of multipotent epithelial cells into eye primordia.
      These nuclear factors act in complex networks to regulate retinal specification
      and appear to be conserved throughout phylogeny. Finally, evidence suggests that
      these nuclear networks have been co-opted to specify cell fates in other tissues.
      We review the latest developments in the field of retinal specification in
      Drosophila and discuss several future directions that remain open for
      investigation.

PMID- 15558483
TI  - Genetics of photoreceptor development and function in zebrafish.
AB  - The vertebrate photoreceptor is a cell of unique morphology and function. It is
      an exquisite light detector, both sensitive and adaptable. Several unusual
      morphological features facilitate photoreceptor function. Signal detection is
      accomplished by a specialized apical structure, the outer segment. There, the
      capture of light produces fluctuations in cell membrane potential, which are then
      transmitted to the downstream circuitry of the retina via a rare type of synaptic
      junction, the ribbon synapse. The development, maintenance and function of the
      vertebrate photoreceptor cell have been studied mainly in four model organisms,
      ranging from an amphibian to man. A teleost fish, the zebrafish, is an important
      recent addition to this group. Genetic screens in zebrafish have identified an
      impressive collection of photoreceptor cell mutants, including the absence or
      malformation of specific morphological features as well as functional
      abnormalities. These mutant strains are currently studied using both molecular
      and embryological tools and provide important insights into photoreceptor
      biology.

PMID- 15558484
TI  - A moving wave patterns the cone photoreceptor mosaic array in the zebrafish
      retina.
AB  - In this paper, we describe the embryonic origin and patterning of the planar
      mosaic array of cone photoreceptor spectral subtypes in the zebrafish retina. A
      discussion of possible molecular mechanisms that might generate the cone mosaic
      array considers but discards a model that accounts for formation of neuronal
      mosaics in the inner retina and discusses limitations of mathematical simulations
      that reproduce the zebrafish cone mosaic pattern. The formation and organization
      of photoreceptors in the ommatidia of the compound eye of Drosophila is compared
      with similar features in the developing zebrafish cone mosaic, and a model is
      proposed that invokes spatiotemporally coordinated cell-cell interactions among
      cone progenitors to determine the identity and positioning of cone spectral
      subtypes.

PMID- 15558485
TI  - Neurotrophic regulation of retinal ganglion cell synaptic connectivity: from
      axons and dendrites to synapses.
AB  - This review highlights important events during the morphological development of
      retinal ganglion cells (RGCs), focusing on mechanisms that control axon and
      dendritic arborization as a means to understand synaptic connectivity with
      special emphasis on the role of neurotrophins during structural and functional
      development of RGCs. Neurotrophins and their receptors participate in the
      development of visual connectivity at multiple levels. In the visual system,
      neurotrophins have been shown to exert various developmental influences, from
      guiding the morphological differentiation of neurons to controlling the
      functional plasticity of visual circuits. This review article examines the role
      of neurotrophins, and in particular of BDNF, during the morphological development
      of RGCs, and discusses potential interactions between activity and neurotrophins
      during development of neuronal connectivity.

PMID- 15558487
TI  - Cell death in the developing vertebrate retina.
AB  - Programmed cell death occurs naturally, as a physiological process, during the
      embryonic development of multicellular organisms. In the retina, which belongs to
      the central nervous system, at least two phases of cell death have been reported
      to occur during development. An early phase takes place concomitant with the
      processes of neurogenesis, cell migration and cell differentiation. A later phase
      affecting mainly neurons occurs when connections are established and synapses are
      formed, resulting in selective elimination of inappropriate connections. This
      pattern of cell death in the developing retina is common among different
      vertebrates. However, the timing and magnitude of retinal cell death varies among
      species. In addition, a precise regulation of apoptosis during retinal
      development has been described. Factors such as neurotrophins, among many others,
      and electrical activity influence the survival of retinal cells during the course
      of development. In this paper, we present a summary of these different aspects of
      programmed cell death during retinal development, and examine how these differ
      among different species.

PMID- 15558486
TI  - New views on retinal axon development: a navigation guide.
AB  - The eye is a peripheral outpost of the central nervous system (CNS) where the
      retinal ganglion cells (RGCs) reside. RGC axons navigate to their targets in a
      remarkably stereotyped and error-free manner and it is this process of directed
      growth that underlies the complex organization of the adult brain. The RGCs are
      the only retinal neurons to project into the brain and their peripheral location
      makes them an unusually accessible population of projection neurons for
      experiments involving in vivo gene transfer, anatomical tracing, transplantation
      and in vitro culture. In this paper, we review recent findings that have
      contributed to our understanding of some of the guidance decisions that axons
      make in the developing visual system. We look at two choice points in the
      pathway, the optic nerve head (onh) and the midline chiasm, and discuss evidence
      that supports the idea that key molecules in guiding axon growth at these
      junctures are netrin-1 (onh) and ephrin-B (chiasm). In the optic tectum where RGC
      axon terminals are arrayed in topographic order, we present experimental evidence
      to suggest that in the dorso-ventral dimension, the B-type ephrins and Eph
      receptors are of prime importance, possibly through attractive interactions. This
      complements the anterior-posterior topographic mapping known to be mediated
      through A-type ephrin/Eph repulsive interactions. An emerging theme is that
      guidance molecules such as ephrin-B and netrin-1 have complex patterns of
      restricted expression in the pathway and play multiple and changing roles in axon
      guidance.

PMID- 15558488
TI  - A newt's eye view of lens regeneration.
AB  - In this paper we describe the basic process of lens regeneration in adult newt
      and we pinpoint several issues in order to obtain a comprehensive understanding
      of this ability, which is restricted to only a few salamanders. The process is
      characterized by dynamic changes in the organization of the extracellular matrix
      in the eye, re-entering of the cell cycle and dedifferentiation of the dorsal
      iris pigment epithelial cells. The ability of the dorsal iris to contribute to
      lens regeneration is discussed in light of iris-specific gene expression as well
      as in relation to factors present in the eye.

PMID- 15558489
TI  - Ocular surface epithelial and stem cell development.
AB  - Phenotypic features and developmental events involved in the genesis of the limbo
      corneal and conjunctival epithelia are described. Together, these two epithelia
      define the ocular surface. They derive from a small cohort of optic vesicle
      induced PAX6+ head ectodermal cells that remain on the surface following lens
      vesicle formation by the main PAX6+ cell cohort. Both epithelia are stratified,
      and display wet, non-keratinizing phenotypes. The most significant spatial
      feature of the limbo-corneal epithelium is the segregation of its supporting stem
      and early precursor cells to the limbus, the outer vascularized rim separating
      the cornea from the conjunctiva. These stem cells express ABCG2, a xenobiotic
      transporter present in stem cells from other organs. ABCG2 transport activity
      excludes the DNA dye Hoechst 33342, allowing the isolation of the ocular stem
      cells by flow cytometry, as a unique cohort known as a side 'side population'.
      Limbal stem cells do not form gap junctions and exist as metabolically isolated
      entities. Tracking of expression changes in Cx43, the main gap junction protein
      expressed in both the pre-epithelial ectoderm and in the mature central corneal
      epithelium, indicates that a limbal stem cell phenotype starts developing very
      soon after lens vesicle invagination, in advance of the appearance of any
      recognizable anatomical sub-epithelial limbal feature. Differences in Cx43
      expression also reveal the very early nature of the divergence in limbo-corneal
      and conjunctival lineages. The putative involvement of several early genes,
      including gradients of PAX6 and differences in expression patterns for members of
      the Id or msh gene expression regulators are reviewed.

PMID- 15558490
TI  - Retinal stem cells in vertebrates: parallels and divergences.
AB  - During the development of the nervous system, after a given number of divisions,
      progenitors exit the cell cycle and differentiate as neurons or glial cells. Some
      cells however do not obey this general rule and persist in a progenitor state.
      These cells, called stem cells, have the ability to self-renew and to generate
      different lineages. Understanding the mechanisms that allow stem cells to
      "resist" differentiating stimuli is currently one of the most fascinating
      research areas for biologists. The amphibian and fish retinas, known to contain
      stem cell populations, have been pioneering models for neural stem cell research.
      The Xenopus retina enabled the characterization of the genetic processes that
      occur in the path from a pluripotent stem cell to a committed progenitor to a
      differentiated neuron. More recently, the discovery that avian and mammalian
      retinas also contain stem cell populations, has contributed to the definitive
      view of the adult nervous system of upper vertebrates as a more dynamic and
      plastic structure than previously thought. This has attracted the attention of
      clinicians who are attempting to employ stem cells for transplantation into
      damaged tissue. Research in this area is promising and will represent a key
      instrument in the fight against blindness and retinal dystrophies. In this
      review, we will focus primarily on describing the main characteristics of various
      retinal stem cell populations, highlighting their divergences during evolution,
      and their potential for retinal cell transplantation. We will also give an
      overview of the signaling cascades that could modulate their potential and
      plasticity.

PMID- 15558491
TI  - Retinal stem cells and regeneration.
AB  - The optic vesicle gives rise to several very different epithelial tissues,
      including the neural retina, the pigmented epithelium, the iris, the ciliary
      epithelium of the ciliary body and the optic stalk. Retinal regeneration can
      arise from several different cellular sources; in some species, the process
      involves interconversion, or transdifferentiation, among cells of the different
      tissue types. Therefore, prior to a discussion of retinal regeneration, we will
      briefly discuss current knowledge about the influence of signaling molecules in
      cell fate determination in ocular tissues. Next, we will detail the evidence for
      neurogenesis in the mature retina. Lastly, we will describe various types of
      regenerative phenomena that occur in the retina, from complete regeneration of
      functional retina in fish and amphibians, to the more limited neuronal production
      that occurs in avian and mammalian retinas.

PMID- 15558492
TI  - Anterior segment development relevant to glaucoma.
AB  - Development of the ocular anterior segment involves a series of inductive
      interactions between neural ectoderm, surface ectoderm and periocular mesenchyme.
      The timing of these events is well established but less is known about the
      molecular mechanisms involved. Various genes that participate in these processes
      have been identified. As the roles of more genes are determined, developmental
      pathways and networks will emerge. Here, we focus on recent advances made using
      mouse models. We summarize key morphological events in formation of anterior
      chamber structures, including the aqueous humor drainage structures that are
      involved in intraocular pressure (IOP) regulation and glaucoma. We discuss the
      developmental roles of genes that associate with abnormal anterior segment
      development and elevated IOP or glaucoma (including Bmp4, Cyp1b1, Foxc1, Foxc2,
      Pitx2, Lmx1b and Tyr ) and how some of these genes may fit into developmental
      networks.

PMID- 15558493
TI  - Congenital hereditary cataracts.
AB  - Congenital cataracts are rare and occur in developed countries with a frequency
      of 30 cases among 100,000 births with a further 10 cases being diagnosed during
      childhood. They reflect mainly genetically caused developmental alterations in
      the lens and surrounding ocular tissues. Even if modern Human Genetics has made
      large steps forward in the characterization of human hereditary disorders, the
      underlying developmental processes can only be investigated in model organisms.
      The mouse is such a good model because of its similarity (as a mammal) and its
      genetic characterization. This review brings together our genetic and
      developmental knowledge of congenital, human cataracts with the corresponding
      mouse models. First, early events will be influenced by genes coding for
      transcription factors like Pax6, Pitx3, Maf or Sox. If the lens is maturing,
      mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or
      the structural proteins of the cytosol of the lens fiber cells (the crystallins)
      become more important. From a genetic point of view it becomes obvious that
      cataract-causing mutations are not distributed randomly. The discovery of a broad
      variety of genes important for eye and lens development made much progress in the
      recent years. Nevertheless, there still remains a long list of mutations to be
      characterized and functionally investigated both in mouse and man indicating a
      broad genetic heterogeneity in that which clinicians simply refer to as a
      "cataract".

PMID- 15558494
TI  - Development and pathology of the hyaloid, choroidal and retinal vasculature.
AB  - During embryogenesis, the development and differentiation of the eye requires the
      concomitant formation of the neural/glial elements along with a dense vascular
      network. The adult neural retina is supported by two distinct vascular systems,
      the proper retinal vessels and the choroidal vessels. The two beds differ not
      only in their pattern of embryonic differentiation, but also in their function in
      the adult organism. The retinal vasculature has barrier properties similar to
      those observed in the brain, whereas the choroidal vessels display a highly
      fenestrated phenotype. The hyaloid vasculature is a transient embryonic vascular
      bed which is complete at birth in mammals and regresses contemporaneously with
      the formation of the retinal vasculature. The dependence of the retina on its
      blood supply makes it highly vulnerable to any vascular changes and indeed ocular
      diseases, such as proliferative retinopathy, age-related macular degeneration and
      the hyperplastic primary vitreous, which are associated with abnormalities of the
      different vascular beds of the eye. A number of factors have been implicated in
      developmental and pathological changes in vessel formation and regression,
      including fibroblast growth factors, platelet-derived endothelial growth factor
      and vascular endothelial growth factor, among others. The purpose of this review
      is to describe and discuss new insights into the mechanisms and molecular cues
      involved in the development of the normal and pathological vascular systems of
      the eye. The characterization of the molecules and cell-cell interactions
      involved in the formation, stabilization and regression of new vessels has led to
      the identification of potential control points for therapeutic intervention.

PMID- 15558495
TI  - A whole-genome scan for 24-hour respiration rate: a major locus at 10q26
      influences respiration during sleep.
AB  - Identification of genes causing variation in daytime and nighttime respiration
      rates could advance our understanding of the basic molecular processes of human
      respiratory rhythmogenesis. This could also serve an important clinical purpose,
      because dysfunction of such processes has been identified as critically important
      in sleep disorders. We performed a sib-pair-based linkage analysis on ambulatory
      respiration rate, using the data from 270 sibling pairs who were genotyped at 374
      markers on the autosomes, with an average distance of 9.65 cM. Uni- and
      multivariate variance-components-based multipoint linkage analyses were performed
      for respiration rate during three daytime periods (morning, afternoon, and
      evening) and during nighttime sleep. Evidence of linkage was found at chromosomal
      locations 3q27, 7p22, 10q26, and 22q12. The strongest evidence of linkage was
      found for respiration rate during sleep, with LOD scores of 2.36 at 3q27, 3.86 at
      10q26, and 1.59 at 22q12. In a simultaneous analysis of these three loci, >50% of
      the variance in sleep respiration rate could be attributed to a quantitative
      trait loci near marker D10S1248 at 10q. Genes in this area (GFRA1, ADORA2L, FGR2,
      EMX2, and HMX2) can be considered promising positional candidates for genetic
      association studies of respiratory control during sleep.

PMID- 15558496
TI  - Strong evidence of linkage disequilibrium between polymorphisms at the IRF6 locus
      and nonsyndromic cleft lip with or without cleft palate, in an Italian
      population.
AB  - Cleft lip with or without cleft palate (CL/P) is one of the most common birth
      defects, but its etiology is largely unknown. It is very likely that both genetic
      and environmental factors contribute to this malformation. Mutations in the gene
      for interferon regulatory factor 6 (IRF6) have been shown to be the cause of Van
      der Woude syndrome, a dominant disorder that has CL/P as a common feature.
      Recently, it has been reported that genetic polymorphisms at the IRF6 locus are
      associated with nonsyndromic CL/P, with stronger association in Asian and South
      American populations. We investigated four markers spanning the IRF6 locus, using
      the transmission/disequilibrium test. A sample of 219 Italian triads of patients
      and their parents were enrolled in the study. Strong evidence of linkage
      disequilibrium was found between markers and disease in both single-allele
      (P=.002 at marker rs2235375) and haplotype (P=.0005) analyses. These findings
      confirm the contribution of IRF6 in the etiology of nonsyndromic CL/P and
      strongly support its involvement in populations of European ancestry.

PMID- 15558497
TI  - Extreme heterogeneity in the molecular events leading to the establishment of
      chiasmata during meiosis i in human oocytes.
AB  - In humans, ~50% of conceptuses are chromosomally aneuploid as a consequence of
      errors in meiosis, and most of these aneuploid conceptuses result in spontaneous
      miscarriage. Of these aneuploidy events, 70% originate during maternal meiosis,
      with the majority proposed to arise as a direct result of defective crossing over
      during meiotic recombination in prophase I. By contrast, <1%-2% of mouse germ
      cells exhibit prophase I-related nondisjunction events. This disparity among
      mammalian species is surprising, given the conservation of genes and events that
      regulate meiotic progression. To understand the mechanisms that might be
      responsible for the high error rates seen in human females, we sought to further
      elucidate the regulation of meiotic prophase I at the molecular cytogenetic
      level. Given that these events occur during embryonic development in females,
      samples were obtained during a defined period of gestation (17-24 weeks). Here,
      we demonstrate that human oocytes enter meiotic prophase I and progress through
      early recombination events in a similar temporal framework to mice. However, at
      pachynema, when chromosomes are fully paired, we find significant heterogeneity
      in the localization of the MutL homologs, MLH1 and MLH3, among human oocyte
      populations. MLH1 and MLH3 have been shown to mark late-meiotic nodules that
      correlate well with--and are thought to give rise to--the sites of reciprocal
      recombination between homologous chromosomes, which suggests a possible 10-fold
      variation in the processing of nascent recombination events. If such variability
      persists through development and into adulthood, these data would suggest that as
      many as 30% of human oocytes are predisposed to aneuploidy as a result of
      prophase I defects in MutL homolog-related events.

PMID- 15558498
TI  - Regression mapping of association between the human leukocyte antigen region and
      Graves disease.
AB  - The human leukocyte antigen class II genes DRB1, DQB1, and DQA1 are associated
      with Graves disease (GD), but, because of strong linkage disequilibrium within
      this region, the primary etiological variant(s) remains unknown. In the present
      study, 871 patients with GD and 621 control subjects were genotyped at the DRB1,
      DQB1, and DQA1 loci. All three loci were associated with GD (P=1.45 x 10(-12),
      P=3.20 x 10(-5), and P=9.26 x 10(-12), respectively). Stepwise logistic
      regression analysis showed that the association could be explained by either DRB1
      or DQA1 but not by DQB1. To extend previous results, the amino acid sequence of
      the exon 2-encoded peptide-binding domain of DRB1 was predicted for each subject,
      and, by use of logistic regression, each position was analyzed for association
      with GD. Of 102 amino acids, 70 were uninformative; of the remaining 32 amino
      acids, 13 were associated with GD (P values ranged from 2.20 x 10(-4) to 1.2 x
      10(-12)). The strongest association was at position beta 74. This analysis is
      consistent with the possibility that position beta 74 of exon 2 of the DRB1
      molecule may have a specific and central role in autoantigen presentation by DRB1
      to T lymphocytes. However, we cannot yet exclude a primary role for DQA1 or for
      other polymorphisms that affect DRB1 function or expression.

PMID- 15558499
TI  - The Clinician Investigator program in companion animal internal medicine at north
      Carolina State University.
AB  - A retrospective study was conducted to describe the development and evolution of
      the combined internal medicine/PhD program, the Clinician Investigator (CI)
      Program, at North Carolina State University. Separate survey instruments were
      developed for individuals who had committed to completing both the residency and
      PhD components and for graduate advisors of individuals who were granted the PhD
      degree. Results are summarized here. Most CIs reported believing that each
      component of the program (clinical training and research training) provided
      mutual benefits and that their teaching skills were enhanced, particularly as a
      result of instructing students in the Veterinary Teaching Hospital. Opinions
      among both the CIs and the graduate advisors were divided about the benefits of a
      combined program compared with a sequential program; however, all but one of 11
      CIs who completed the survey would enroll in the combined program again. The
      graduate advisors were overwhelming positive about the CIs they had advised and
      indicated that they would welcome a CI as a PhD student in their laboratory
      again. Suggested areas for improvement included guaranteed salary/stipend support
      for the average time to completion (six years) instead of for five years, as well
      as more emphasis on and guidance in identifying a graduate advisor earlier in the
      CI program so as to smooth the transition between the clinical and research
      training components of the program. It is hoped that other training programs will
      benefit from the summary of our experience with this program.

PMID- 15558500
TI  - Introduction. Non-small cell lung cancer: some important questions to be solved.

PMID- 15558501
TI  - Radiation esophagitis: Predictive factors and preventive strategies.
AB  - Radiation esophagitis remains the primary dose-limiting acute toxicity in the
      radiotherapeutic management of thoracic neoplasms. Improved understanding of this
      toxicity will facilitate dose escalation and enhancement of the therapeutic
      ratio. This article reviews the predictive factors and preventive strategies for
      radiation esophagitis. In particular, clinical and dosimetric studies predicting
      the risk of radiation esophagitis are analyzed. The critical impact of
      chemotherapy on radiation esophagitis is characterized. Preventive strategies to
      minimize this toxicity also are explored. Overall, this article reviews the
      current understanding of radiation toxicity for the esophagus.

PMID- 15558502
TI  - Radiation dose escalation in non-small cell carcinoma of the lung.

PMID- 15558503
TI  - Non-small cell lung cancer and central nervous system metastases: should we be
      using prophylactic cranial irradiation?
AB  - Central nervous system (CNS) failure in patients with locally advanced non-small
      cell; lung cancer (LA-NSCLC) is a common and debilitating problem. Standard
      follow-up after local regional therapy does not include routine radiologic
      evaluation of the brain. Imaging is performed at the onset of symptoms followed
      by palliative therapy for CNS failure. Some investigators support regular
      screening with therapy for failures before the onset of symptoms. This
      alternative may decrease the impact of CNS failures and lengthen survival. Other
      investigators have shown that prophylactic cranial irradiation (PCI) for LA-NSCLC
      decreases the incidence of CNS failures. The potential survival, quality of life,
      and neuropsychological advantage or disadvantage of these two approaches has not
      been systematically studied. This article will review the problem of CNS failures
      in patients with LA-NSCLC and the potential risks and benefits of close
      observation and PCI. The necessity of conducting an ambitious study evaluating
      the potential survival advantage of PCI will be discussed.

PMID- 15558504
TI  - A practical approach to pulmonary risk assessment in the radiotherapy of lung
      cancer.
AB  - The risk of lung injury is a significant limiting factor in the use of thoracic
      radiotherapy for lung cancer. Given the high mortality and local failure rates in
      patients with unresectable lung cancer, a goal has been to increase the dose to
      the tumor as much as possible while trying to limit the damage to normal tissue.
      Efforts have been made to predict the risks for lung injury pretreatment, based
      on the planned dose and volume of lung treated, with mixed results. Complicating
      factors include performance status, underlying medical conditions, possible
      genetic predisposition to injury, and tumor location-associated changes in lung
      function. Much as a thoracic surgeon stratifies a patient's risk for pulmonary
      morbidity before resection, radiation oncologists should perform an assessment of
      patient specific factors that will impact on the potential toxicity of a given
      course of treatment. We present a proposed approach to the evaluation, risk
      assessment, and follow-up of patients treated with thoracic radiotherapy for lung
      cancer.

PMID- 15558505
TI  - Defining target volumes for non-small cell lung carcinoma.
AB  - The definition of target volumes for non-small cell lung carcinoma (NSCLC)
      remains a controversial topic as tradition-based approaches of the past are being
      critically re-evaluated in the light of the advent of three-dimensional treatment
      techniques, by the awareness of the poor local control achieved using current
      treatment fields and radiation doses, and by the major improvements in
      noninvasive staging that enable the gross tumor volume to be established with
      greater accuracy. This article reviews the current knowledge and remaining
      uncertainties in defining target volumes for NSCLC. The use of these new
      approaches may allow for improvements in the therapeutic ratio of radiotherapy in
      NSCLC.

PMID- 15558506
TI  - Adjuvant chemotherapy and radiotherapy in non-small cell lung cancer.
AB  - Although surgical resection remains the best potentially curative treatment for
      non-small cell lung cancer (NSCLC), more than half the patients undergoing
      resection will eventually die of recurrent disease. Approximately two thirds of
      relapses occur outside the chest, indicating a potential role for adjuvant
      chemotherapy. Indeed, a meta-analysis has suggested an absolute survival benefit
      of 5% at 5 years with adjuvant cisplatin-based regimens. This finding has incited
      several large-scale randomized trials, the largest of which, the International
      Adjuvant Lung Trial, has confirmed a similar survival advantage. Conversely, a
      meta-analysis on postoperative radiotherapy has suggested a detrimental effect,
      especially for stage I and II patients, that is related most probably to a poor
      radiation technique. Its value for stage III remains controversial: the observed
      reduction in local failure did not translate into a survival benefit. In this
      article, the current status of adjuvant chemotherapy and radiotherapy are
      reviewed, and future prospects are discussed.

PMID- 15558507
TI  - Response to radiation.
AB  - Computed tomography (CT) has traditionally been the standard radiographic
      modality for diagnosing and monitoring non-small cell; lung cancer (NSCLC) after
      treatment. Given the limitations of CT, the utility of 18F-fluoro-2-deoxy-glucose
      positron emission tomography (FDG-PET) has been investigated for the management
      of NSCLC, with promising findings. Its adjunctive role with CT in diagnosing and
      staging disease is well established. FDG-PET also has been found to be a valuable
      tool for radiation treatment planning because it improves the precision of lesion
      definition. More recently, its value for determining clinical response both
      during and after treatment has been explored. This review highlights the various
      applications of FDG-PET in the diagnosis and management of NSCLC as corroborated
      by clinical data, with considerations of future directions.

PMID- 15558508
TI  - Management of unresectable stage III non-small cell lung cancer: the role of
      combined chemoradiation.
AB  - Until the late 1980s, thoracic radiation therapy (TRT) was considered the
      standard of care for patients with stage III disease despite extremely poor 5
      year survival rates. Several studies evaluating TRT combined with chemotherapy
      showed a survival advantage. Based on these data, combined modality therapy
      became accepted as the standard of care in this group of patients with good
      performance status and made the treatment of locally advanced non-small cell lung
      cancer (NSCLC) a multidisciplinary endeavor. Recent studies have shown that
      concurrent chemoradiotherapy offers a significantly greater survival advantage
      than sequential chemoradiotherapy and should be considered standard of care in
      stage III inoperable NSCLC. Although numerous Phase III trials have clearly
      demonstrated a survival benefit in those patients who receive combined modality
      therapy, many questions remain. The most effective combination of drugs, their
      optimal mode of administration, the use of either induction or consolidation
      therapy in addition to a backbone of concurrent therapy, and the details of TRT,
      including total dose, fractionation, acceleration, treatment volumes, and tumor
      targeting remain important issues to define. Although progress has been made in
      treatment for locally advanced NSCLC, the majority of patients still die within 5
      years either from locoregional or distant progression of disease. This article
      will review the current data regarding treatment of this heterogeneous group of
      patients. In addition, a brief summary of new molecular therapies and
      chemotherapeutics will be presented.

PMID- 15558509
TI  - The potential role of surgery after induction treatment.
AB  - Induction treatment is the initial therapy that is administered before any
      locoregional procedure. In this article, the history of preoperative chemotherapy
      or chemoradiotherapy followed by induction chemoradiotherapy, in locally advanced
      non-small cell lung cancers (stages III A and B) is discussed, as well as the
      selection of an optimal subset of patients for induction strategies. In addition,
      the prognostic effects of response to treatment and/or surgical resection as
      recently reported in published clinical trials are analyzed. Finally, we conclude
      that mediastinal nodal downstaging after induction therapy significantly improves
      the survival of patients who are surgically resected after induction.

PMID- 15558510
TI  - Quiz page. A brown tumor in the sixth right rib secondary to hyperparathyroidism.

PMID- 15558511
TI  - Expanded-spectrum beta-lactamase producing Klebsiella pneumoniae-related
      peritonitis in a patient on peritoneal dialysis.
AB  - While hospitalized for pneumonia with ventilator-dependent respiratory failure, a
      45-year-old man on continuous ambulatory peritoneal dialysis (CAPD) had
      nosocomial peritonitis secondary to infection by expanded spectrum beta-lactamase
      producing Klebsiella pneumoniae (ESBL-Kp). He was treated successfully with a 3
      week course of intraperitoneal (IP) flomoxef therapy without subsequent relapse,
      loss of peritoneal catheter, ultrafiltration failure, or dialysis inadequacy. The
      International Consensus Panel recommends IP ceftazidime as the treatment of
      choice for CAPD patients suffering Klebsiella species-related peritonitis.
      However, the most appropriate form of IP antibiotic therapy and the outcomes for
      expanded-spectrum beta-lactamase (ESBL)-producing bacteria-related peritonitis
      for CAPD patients have not been established yet. Further, the ability to
      correctly report minimal inhibitory concentrations (MICs) of ceftazidime for ESBL
      bacteria in the resistant range varies between laboratories, making the diagnosis
      of ESBL-Kp-related CAPD peritonitis more complex and difficult. Thus, it appears
      reasonable to suggest that its incidence is probably underestimated and its
      significance ignored. The authors suggest that a 3-week IP treatment with
      flomoxef, a synthesized oxacephem, with loading and maintenance doses of 250 and
      125 mg/L, respectively, is effective and safe for ESBL-Kp-related peritonitis in
      these patients. ESBL producing bacterial infection should be considered as a
      possible cause of overt CAPD-related peritonitis. Early detection of ESBLB
      pathogens and institution of effective antibiotic treatment may improve the
      prognosis.

PMID- 15558512
TI  - Unmasking hypotension by beta lactam during dextran sulfate low-density
      lipoprotein apheresis.
AB  - The authors report, for the first time, potentially fatal adverse effects of
      combined treatment using beta lactam and low-density lipoprotein (LDL) apheresis
      with dextran sulfate adsorption. A 62-year-old man was receiving LDL apheresis
      because of peripheral artery disease. Cefmetazole was administered to treat
      infection of a leg ulcer. Although antibiotics alone did not cause any allergic
      reactions, he manifested circulatory collapse during LDL apheresis. Possible
      mechanisms for shock were discussed.

PMID- 15558514
TI  - Ischemic optic neuropathy in dialyzed patients: a previously unrecognized
      manifestation of calcific uremic arteriolopathy.
AB  - Two patients with end-stage renal disease and on long-term hemodialysis presented
      with hypotension and an acute unilateral loss of vision. A diagnosis of anterior
      ischemic optic neuropathy (AION) was made quickly, but despite high-dose steroid
      therapy, significant vision was not recovered. Temporal artery biopsy results
      showed extensive medial calcification. The possibility that hypotension, when
      coupled with calcific uremic arteriolopathy in arteries supplying the optic nerve
      head, will lead to AION in dialyzed patients is discussed. A short review of AION
      in the dialysis population is given.

PMID- 15558515
TI  - Propofol infusion syndrome: an unusual cause of renal failure.
AB  - Propofol infusion syndrome has been increasingly recognized as a syndrome of
      unexplained myocardial failure, metabolic acidosis, and rhabdomyolysis with renal
      failure. It has been described only with acute neurologic injury or acute
      inflammatory diseases complicated by severe infections or sepsis. It appears to
      develop in the context of high-dose, prolonged propofol (100 microg/kg/min)
      treatment in combination with catecholamines and/or steroids. This was first
      noted in children but is increasingly recognized in adults. This is a case report
      of 2 patients (a 42-year-old man and a 17-year-old girl) who had acute renal
      failure associated with use of propofol in the appropriate clinical setting. It
      examines the pathophysiology and the possible mechanisms of this condition and
      illustrates the need to consider it as the cause of rhabdomyolysis and acute
      renal failure in critically ill patients.

PMID- 15558516
TI  - Effect of dialysis modality on plasma fibrinogen concentration: a meta-analysis.
AB  - BACKGROUND: Concentrations of plasma fibrinogen, a vascular risk factor, tend to
      be greater in patients on peritoneal dialysis (PD) than hemodialysis (HD)
      therapy, like concentrations of serum cholesterol, lipoprotein(a), and
      transthyretin, despite the substantial loss of protein during PD. Worse vascular
      outcome has been noted in PD patients compared with HD patients in several
      studies. METHODS: In this study, the mean difference in plasma fibrinogen levels
      (PD-HD) was quantified by means of meta-analysis of mean differences found in 12
      cohorts with both PD and HD patients (set 1; N = 630) by using a fixed-effects
      model and meta-analysis of mean fibrinogen values reported in 30 cohorts of
      patients on a single dialysis modality (set 2; 8 PD cohorts, 22 HD cohorts; N =
      2,096) by using a mixed model. RESULTS: On meta-analysis, the weighted mean
      difference (PD-HD) was 105 mg/dL (95% confidence interval [CI], 86 to 124 [3.1
      micromol/L; 95% CI, 2.5 to 3.6]) in set 1 and 103 mg/dL (95% CI, 53 to 153 [3.0
      micromol/L; 95% CI, 1.6 to 4.5) in set 2. CONCLUSION: Like other vascular risk
      factors, such as cholesterol and lipoprotein(a), plasma fibrinogen level is
      markedly greater in PD than HD patients, with an approximate difference of 100
      mg/dL [2.9 mumol/L]. Different plasma reference ranges for fibrinogen need to be
      defined for PD and HD patients. The mechanism for the difference and the possible
      role of hyperfibrinogenemia in worsening vascular disease in PD patients deserve
      study.

PMID- 15558517
TI  - High-protein diets: potential effects on the kidney in renal health and disease.
AB  - High-protein (HP) weight-loss diets have existed in the United States for
      decades, although their popularity has recently surged as obesity has become more
      common. Despite their widespread use, valid concerns exist that HP diets may
      induce clinically important alterations in renal function and health. HP
      consumption has been found, under various conditions, to lead to glomerular
      hyperfiltration and hyperemia; acceleration of chronic kidney disease (CKD);
      increased proteinuria; diuresis, natriuresis, and kaliuresis with associated
      blood pressure changes; increased risk for nephrolithiasis; and various metabolic
      alterations. Unfortunately, a comprehensive understanding of the implications of
      HP diets is limited by the lack of a universally accepted definition for HP
      intake, a paucity of rigorous long-term human interventional studies that
      necessitate relying on short-term or fairly circumstantial evidence, and sparse
      data on the effects of HP consumption in obese individuals. In addition, matters
      are further complicated because the renal impact HP diets for limited periods is
      most likely different than that for more chronic consumption. Nevertheless,
      although there are no clear renal-related contraindications to HP diets in
      individuals with healthy kidney function, the theoretical risks should be
      reviewed carefully with the patient. In contrast, HP diets have the potential for
      significant harm in individuals with CKD and should be avoided if possible.
      Because CKD is often a silent disease, all individuals should undergo a screening
      serum creatinine measurement and urinary dipstick test for proteinuria before the
      initiation of such a diet.

PMID- 15558518
TI  - Genetics of hypercalciuria and calcium nephrolithiasis: from the rare monogenic
      to the common polygenic forms.
AB  - Idiopathic calcium nephrolithiasis is a multifactorial disease with a
      pathogenesis that involves a complex interaction of environmental and individual
      factors. This review discusses what is known about monogenic renal calcium stone
      related disorders, provides an update on genetic research in calcium
      nephrolithiasis and such intermediate phenotypes as idiopathic hypercalciuria,
      discusses the problems that these conditions pose to clinicians and geneticists
      interested in their pathogenesis, and proposes some method tools potentially
      useful in this research frame of reference.

PMID- 15558519
TI  - Uromodulin storage diseases: clinical aspects and mechanisms.
AB  - The recent discovery of mutations in the uromodulin gene ( UMOD ) in patients
      with medullary cystic kidney disease type 2 (MCKD2), familial juvenile
      hyperuricemic nephropathy (FJHN), and glomerulocystic kidney disease (GCKD)
      provides the opportunity for a revision of pathogenic aspects and puts forth the
      basis for a renewed classification. This review focuses on clinical,
      pathological, and cell biology advances in UMOD -related pathological states,
      including a review of the associated clinical conditions described to date in the
      literature. Overall, 31 UMOD mutations associated with MCKD2 and FJHN (205
      patients) and 1 mutation associated with GCKD (3 patients) have been described,
      with a cluster at exons 4 and 5. Most are missense mutations causing a cysteine
      change in uromodulin sequence. No differences in clinical symptoms between
      carriers of cysteine versus polar residue changes have been observed; clinical
      phenotypes invariably are linked to classic MCKD2/FJHN. A common motif among all
      reports is that many overlapping symptoms between MCKD2 and FJHN are present, and
      a separation between these 2 entities seems unwarranted or redundant. Cell
      experiments with mutant variants indicated a delay in intracellular maturation
      and export dynamics, with consequent uromodulin storage within the endoplasmic
      reticulum (ER). Patchy uromodulin deposits in tubule cells were found by means of
      immunohistochemistry, and electron microscopy showed dense fibrillar material in
      the ER. Mass spectrometry showed only unmodified uromodulin in urine of patients
      with UMOD mutations. Lack of uromodulin function(s) is associated with
      impairments in tubular function, particularly the urine-concentrating process,
      determining water depletion and hyperuricemia. Intracellular uromodulin trapping
      within the ER probably has a major role in determining tubulointerstitial
      fibrosis and renal failure. We propose the definition of uromodulin storage
      diseases for conditions with proven UMOD mutations.

PMID- 15558520
TI  - A randomized controlled trial comparing intermittent with continuous dialysis in
      patients with ARF.
AB  - BACKGROUND: Despite the widespread use of continuous renal replacement therapy in
      critically ill patients with acute renal failure (ARF), there are few data
      supporting its benefits over conventional intermittent hemodialysis (IHD). We
      sought to analyze differences in survival between modalities in a study that
      compared continuous venovenous hemodialysis (CVVHD) with IHD. METHODS: Eighty
      critically ill patients with ARF requiring dialysis were randomized after
      stratification by severity of illness to treatment with CVVHD or IHD. RESULTS:
      There were no differences in survival or renal recovery between groups. In
      patients who died, mean survival time was 10.7 +/- 11.2 days for the IHD group
      versus 14.3 +/- 16.1 days for the CVVHD group (P = not significant). There was
      greater net volume removal in the CVVHD group during 72 hours. Declines in urine
      output during 72 hours were similar between groups. Mean arterial pressure off
      and on dialysis therapy was analyzed retrospectively. There was a significant
      decrease in mean arterial pressure for patients on IHD therapy not seen in those
      on CVVHD therapy, but this did not lead to a survival advantage. CONCLUSION:
      Despite greater volume control, CVVHD did not lead to an improvement in survival,
      preservation of urine output, or renal recovery compared with IHD in patients
      with ARF.

PMID- 15558521
TI  - Resting energy expenditure of chronic kidney disease patients: influence of renal
      function and subclinical inflammation.
AB  - BACKGROUND: The resting energy expenditure (REE) of patients with chronic kidney
      disease (CKD) might be influenced by the degree of renal function and by a
      subclinical inflammatory condition. The aim of this study is to evaluate the
      impact of these 2 variables on the REE of patients with CKD. METHODS: A cross
      sectional study was performed on 91 nondialyzed and nondiabetic patients with CKD
      with no clinical signs of inflammation. Patients were divided into quartiles of
      creatinine clearance (CrCl) and tertiles of C-reactive protein (CRP) level. REE
      was measured by means of indirect calorimetry, and the presence of a subclinical
      inflammatory condition was assessed by means of serum CRP concentration. RESULTS:
      CrCl interquartile ranges calculated were: quartile 1 (CrCl < or = 18 mL/min [<
      or =0.30 mL/s]; n = 24); quartile 2 (CrCl, 19 to 29 mL/min [0.31 to 0.48 mL/s]; n
      = 22); quartile 3 (CrCl, 30 to 42 mL/min [0.49 to 0.70 mL/s]; n = 23), and
      quartile 4 (CrCl > or = 43 mL/min [> or =0.71 mL/s]; n = 22). Nonadjusted REE and
      REE adjusted for sex, age, and lean body mass did not differ among the 4 CrCl
      quartiles. The following ranges were calculated for CRP tertiles: tertile 1 (CRP
      < or = 0.14 mg/dL; n = 30), tertile 2 (CRP, 0.15 to 0.49 mg/dL; n = 31), and
      tertile 3 (CRP > or = 0.50 mg/dL; n = 30). The nonadjusted REE in CRP tertile 3
      was significantly greater than those in tertiles 1 and 2. REE adjusted for sex,
      age, and lean body mass was greater in CRP tertile 3 than tertile 1, a difference
      equivalent to 123.7 kcal/d (P = 0.003; 95% confidence interval, 42.9 to 204.5). A
      borderline difference was observed between CRP tertiles 3 and 2. When analyzing
      the entire group, REE did not correlate with either serum creatinine level or
      CrCl, and a borderline correlation between REE and log of CRP was observed (r =
      0.19; P = 0.07). CONCLUSION: This study suggests that REE is not influenced by
      degree of renal function, but it may be elevated during a condition of
      subclinical inflammation.

PMID- 15558522
TI  - Anemia and health-related quality of life in adolescents with chronic kidney
      disease.
AB  - BACKGROUND: A number of studies of adults with chronic kidney disease (CKD) have
      shown a negative impact of anemia on several aspects of health-related quality of
      life (HRQOL). Although similar links have been suggested in adolescent dialysis
      populations, the relationship between anemia and HRQOL in children not requiring
      dialysis therapy has yet to be studied extensively in a large sample. METHODS: We
      examined the association between anemia and HRQOL in baseline data collected on a
      prospective cohort of adolescents with CKD by using a generic HRQOL questionnaire
      completed by parents or caregivers (Child Health Questionnaire Parent Form [CHQ
      PF50]). Our study population included guardians or caregivers of 105 adolescents
      (mean age, 14 +/- 2 years) with stages 1 to 5 CKD as defined by the National
      Kidney Foundation-Kidney Disease Outcomes Quality Initiative, including subjects
      with chronic renal insufficiency, patients with functioning kidney transplants,
      and dialysis patients. RESULTS: Seventy of 105 patients were classified in the
      study as anemic according to a hematocrit value of 36% or less. Compared with the
      group with higher hematocrit values and independent of sex, race, and estimated
      glomerular filtration rate, anemic patients reported greater limitations in CHQ
      PF50 domains relating to (1) physical functioning, (2) limitations in schoolwork
      or activities with friends as a result of physical health, and (3) parental
      impact in time and family activities. CONCLUSION: Anemia was associated with
      lower quality of life in adolescents across the spectrum of stages of CKD. Future
      studies should address the effect of interventions to improve anemia on HRQOL.

PMID- 15558523
TI  - Coronary artery calcification in patients with CRF not undergoing dialysis.
AB  - BACKGROUND: Coronary artery calcification (CAC) correlates with the extent of
      coronary atherosclerosis and, consequently, with an increased risk for
      cardiovascular events. CAC is more frequent in uremic patients than in the
      general population. Nearly all data about CAC relate to patients on dialysis
      therapy. This study evaluates the prevalence and extent of CAC in patients with
      chronic renal failure (CRF) not yet on dialysis therapy. METHODS: Consecutive
      outpatients with CRF not on dialysis therapy were enrolled and compared with
      controls (ie, healthy volunteers and patients with essential hypertension with
      normal renal function). Patients and controls were asymptomatic and had no
      previous history of myocardial infarction, coronary bypass surgery, or
      angioplasty. Patients with diabetes were excluded. Clinical characteristics,
      biochemical test results (included homocysteinemia and C-reactive protein level),
      and serum concentrations of calcium, phosphorus, and intact parathyroid hormone
      (iPTH) were evaluated in patients and controls. CACs were searched for and scored
      by means of spiral computed tomography (CT). To assess the CAC progression rate,
      spiral CT was repeated in some patients. RESULTS: Eighty-five patients and 55
      controls were studied. Patients were aged 52 +/- 13 years and had a CRF duration
      of 6.3 +/- 5.6 years, glomerular filtration rate of 33.0 +/- 16.0 mL/min (0.55 +/
      0.27 mL/s), serum calcium level of 9.5 +/- 0.5 mg/dL (2.37 +/- 0.12 mmol/L),
      serum phosphorus level of 4.1 +/- 0.9 mg/dL (1.32 +/- 0.29 mmol/L), and serum
      iPTH level of 143 +/- 121 pg/mL (ng/L). CAC was found in 40% of patients and 13%
      of controls; calcification scores were 422 +/- 634 in patients and 43.9 +/- 33 in
      controls. Only age ( P < 0.001) was a predictor of CAC. In patients with a
      repeated score performed (after a mean of 7.9 months), calcification scores
      increased (from 383 +/- 627 to 682 +/- 890) in 8 of 10 patients. CONCLUSION: CAC
      is already present in the early phase of CRF; the prevalence is greater in
      patients with CRF than in controls, but less than that reported in dialysis
      patients. Serum concentrations of calcium, phosphorus, iPTH, and inflammation
      markers do not predict the appearance or progression of CAC.

PMID- 15558524
TI  - Decreased urinary peptide excretion in patients with renal disease.
AB  - BACKGROUND: Normal urine contains low-molecular-weight peptides or protein
      fragments that have been poorly studied, primarily because of the technical
      difficulty of measuring peptides in the presence of proteins. We studied these
      substances in healthy subjects and patients with renal disease and varying
      degrees of proteinuria to understand the factors that determine their excretion.
      METHODS: We estimated these substances as the difference between results using
      the Lowry method (which detects both proteins and peptides) and those obtained
      using the dye-binding Bradford (Biorad) method (Biorad Laboratories Inc,
      Hercules, CA; which detects only proteins). RESULTS: We validated this 2-assay
      approach to measure peptide levels by showing that such proteins as
      immunoglobulin G, albumin, and lysozyme were measured equally by the Lowry and
      Biorad methods, whereas degraded proteins were recognized by the Lowry method
      only, but not by the Biorad method. We found that healthy subjects excreted less
      than 200 mg of protein, but 3 to 4 g of peptides/g creatinine; thus, peptides
      constituted approximately 95% of total protein material excreted in urine.
      Patients with renal disease and proteinuria had a progressive decrease in peptide
      excretion, ranging from 3 to 0 g/g creatinine. Twenty-five percent of nephrotic
      patients (18 of 72 patients) excreted very small amounts of peptides in urine (0%
      to 10% of total protein material). CONCLUSION: We found that healthy persons
      excrete substantial amounts of peptides in urine, and this excretion decreases in
      the presence of proteinuric renal disease. It is possible that these peptides in
      urine arise from the tubular degradation of filtered proteins and exocytosis of
      protein fragments toward the urinary side, a process that becomes increasingly
      impaired as proteinuria increases.

PMID- 15558525
TI  - Clinicopathologic characteristics of nodular glomerulosclerosis in Chinese
      patients with type 2 diabetes.
AB  - BACKGROUND: Nodular glomerulosclerosis is a distinct entity that is highly
      specific for diabetic glomerulopathy. However, clinicopathologic characteristics
      of this nodular lesion are largely undefined in patients with type 2 diabetes.
      METHODS: An autopsy study was conducted to investigate the clinical,
      histopathologic, and histochemical characteristics of 351 consecutive cases with
      type 2 diabetes. In addition, immunohistochemical staining was performed in a
      representative subset of 50 cases. RESULTS: Nodular glomerulosclerosis was found
      in 37.6%. Hypertension, elevated serum creatinine and urea levels, renal failure,
      myocardial infarction, low body mass index, and large glomerular matrix area were
      the significant risk factors for nodular glomerulosclerosis. Proteinuria (protein
      > 0.5 g/24 h), renal insufficiency (serum creatinine > or = 2.0 mg/dL [> or =178
      micromol/L]), and renal failure were found in 28.1%, 33.6%, and 7.6% of patients
      with type 2 diabetes with nodular glomerulosclerosis, respectively. Glomerular
      matrix fractions were 42.1% +/- 13.3%, 32.3% +/- 15.3%, and 22.7% +/- 8.0% in
      patients with nodular glomerulosclerosis, non-nodular glomerulopathy
      (glomerulopathy in the absence of Kimmelstiel-Wilson nodule), and near-normal
      glomeruli with age-related minimal changes, respectively (analysis of variance, P
      < 0.001). Immunoreactivity for collagen type IV, fibronectin, and laminin was
      localized at the periphery of mesangial nodules. Mesangial cells at the periphery
      of mesangial nodules showed increased staining intensity for alpha-smooth muscle
      actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1). Nodular
      lesions also showed a marked increase in number of glomerular CD68-positive
      macrophages. CONCLUSION: In patients with type 2 diabetes, nodular
      glomerulosclerosis is related to hypertension, advanced renal disease, and
      prevalent myocardial infarction. Glomerular macrophage infiltration, expression
      of alpha-SMA by mesangial cells, and overexpression of TGF-beta1 are the cellular
      changes associated with abnormal extracellular matrix deposition in nodular
      glomerulosclerosis.

PMID- 15558526
TI  - New subcategories of class IV lupus nephritis: are there clinical, histologic,
      and outcome differences?
AB  - BACKGROUND: The International Society of Nephrologists and Renal Pathology
      Society (ISN/RPS) classification of lupus nephritis proposes a controversial
      subclassification of class IV lupus nephritis into IV-segmental (IV-S) and IV
      global (IV-G). METHODS: A retrospective analysis of a biopsy-proven cohort of
      patients with lupus nephritis using the ISN/RPS classification was performed.
      RESULTS: The prevalence of class IV was 47% in the cohort of 70 patients with
      lupus nephritis. Of 33 patients with class IV lupus nephritis, 11 patients had
      class IV-S and 22 patients had class IV-G. There were no significant differences
      in age, sex, and ethnicity in the 2 groups. Greater serological activity (lower
      C4 level) was observed in the IV-S group, whereas serum creatinine levels and
      diastolic blood pressures were significantly greater in the IV-G group.
      Hematocrit levels, significant proteinuria (urine protein > or =3 + ), duration
      of systemic lupus erythematosus, and the Systemic Lupus Erythematosus Disease
      Activity Index were similar in the 2 groups. Histologically, combined lesions
      with segmental endocapillary proliferation and fibrinoid necrosis were
      significantly more frequent in the IV-S group. The percentage of glomeruli with
      cellular crescents also was greater in the IV-S group, but the difference was not
      significant. Wire loops were more common in the IV-G group. Transformation to IV
      G was observed in 2 of 3 specimens from repeated biopsies available in the IV-S
      group; greater than 50% of the IV-G group had both segmental and global
      glomerular involvement. No significant difference was detected in outcomes in the
      2 groups after average follow-ups of 38 and 55 months in the IV-S and IV-G
      groups, respectively. CONCLUSION: A clinical and prognostic distinction between
      IV-S and IV-G remains to be proven.

PMID- 15558527
TI  - Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium
      oxalate stone formers and non-stone formers.
AB  - BACKGROUND: Increased rates of either oxalate absorption or endogenous oxalate
      synthesis can contribute to hyperoxaluria, a primary risk factor for the
      formation of calcium oxalate-containing kidney stones. This study involves a
      comparative assessment of oxalate absorption and endogenous oxalate synthesis in
      subpopulations of stone formers (SFs) and non-stone formers (NSFs) and an
      assessment of the effect of ascorbate supplementation on oxalate absorption and
      endogenous oxalate synthesis. METHODS: Twenty-nine individuals with a history of
      calcium oxalate kidney stones (19 men, 10 women) and 19 age-matched NSFs (8 men,
      11 women) participated in two 6-day controlled feeding experimental periods:
      ascorbate-supplement (2 g/d) and no-supplement treatments. An oxalate load
      consisting of 118 mg of unlabeled oxalate and 18 mg of 13C2 -oxalic acid was
      administered the morning of day 6 of each experimental period. RESULTS: Mean 13C2
      -oxalic acid absorption averaged across the ascorbate and no-supplement
      treatments was significantly greater in SFs (9.9%) than NSFs (8.0%). SFs also had
      significantly greater 24-hour post-oxalate load urinary total oxalate and
      endogenous oxalate levels with both treatments. Twenty-four-hour urinary total
      oxalate level correlated strongly with both 13C2 -oxalic acid absorption (SFs, r
      = 0.76; P < 0.01; NSFs, r = 0.62; P < 0.01) and endogenous oxalate synthesis
      (SFs, r = 0.95; P < 0.01; NSFs, r = 0.92; P < 0.01). CONCLUSION: SFs are
      characterized by greater rates of both oxalate absorption and endogenous oxalate
      synthesis, and both these factors contribute to the hyperoxaluric state. The
      finding that ascorbate supplementation increased urinary total and endogenous
      oxalate levels suggested that this practice is a risk factor for individuals
      predisposed to kidney stones.

PMID- 15558528
TI  - Pharmacokinetics, pharmacodynamics, and safety of cinacalcet hydrochloride in
      hemodialysis patients at doses up to 200 mg once daily.
AB  - BACKGROUND: Cinacalcet hydrochloride (HCl) can be used to manage the secondary
      hyperparathyroidism of patients with chronic kidney disease. This study
      investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of
      cinacalcet HCl over a dose range of 25 to 300 mg/d in patients receiving
      dialysis. METHODS: Hemodialysis patients were randomly assigned 4:1 to receive
      cinacalcet HCl or placebo in this double-blind study. Cinacalcet HCl doses were
      escalated weekly in 25-mg increments from 25 to 300 mg/d. Noncompartmental
      methods were used to analyze the pharmacokinetic parameters of cinacalcet (the
      free-base). The effects of cinacalcet concentration on plasma parathyroid hormone
      (PTH) and serum calcium levels were evaluated. RESULTS: Of 23 patients enrolled
      (17 patients, cinacalcet HCl; 6 patients, placebo), 10 patients (8 patients,
      cinacalcet HCl; 2 patients, placebo) completed the study. Plasma concentration,
      median area under the plasma concentration-time curve from time 0 to 24 hours
      after dosing, and maximal plasma concentration (Cmax ) of cinacalcet increased
      with doses up to 200 mg once daily. Median oral clearance ranged from 222 to 599
      L/h, and median time after dosing when C max occurred ranged from 2 to 3 hours
      across all doses. The pharmacokinetics were linear over the 25- to 200-mg once
      daily dose range, with no substantial increase in exposure at greater than 200
      mg. Changes in plasma PTH concentrations correlated inversely with cinacalcet
      concentration. The concentration-effect relationship was well described by an
      inhibitory maximal effect model. Cinacalcet HCl was reasonably tolerated, and the
      incidence of adverse events was similar between groups (76%, cinacalcet; 80%,
      placebo). Gastrointestinal events were noted at greater doses and may be dose
      related. CONCLUSION: Cinacalcet HCl shows a dose-proportional increase in
      exposure over the range of 25 to 200 mg once daily in patients on hemodialysis
      therapy, and kinetics were linear up to 200 mg once daily. The incidence of
      adverse events was similar between groups.

PMID- 15558529
TI  - Long-term survival of dialysis patients with bacterial endocarditis in the United
      States.
AB  - BACKGROUND: The incidence of bacterial endocarditis is much greater in long-term
      dialysis patients compared with the general population, and chronic kidney
      disease has been postulated as an independent host-related risk factor. Limited
      data are available on the long-term survival of dialysis patients with
      endocarditis. METHODS: Dialysis patients hospitalized for bacterial endocarditis
      between 1977 and 2000 were studied retrospectively using data from the US Renal
      Data System database. Long-term survival was estimated by means of the life-table
      method. A Cox proportional hazards model was used to identify the impact of
      demographic characteristics and comorbidity on outcome. RESULTS: A total of
      13,130 dialysis patients with bacterial endocarditis were identified. The in
      hospital mortality rate for the entire cohort was 23.5%. Survival rates at 1, 2,
      3, and 5 years were 45.9%, 33.3%, 24.3%, and 14.7% for patients hospitalized
      between 1977 and 1991 and 41.0%, 29.1%, 20.6%, and 10.9% for those hospitalized
      between 1992 and 1996, respectively. Survival rates at 1, 2, and 3 years were
      38.4%, 25.3%, and 18.3% for patients hospitalized between 1997 and 2000,
      respectively. The most powerful independent predictors of all-cause death were
      age, diabetes as cause of end-stage renal disease, and cerebrovascular accident
      or transient ischemic attack as a comorbid condition. CONCLUSION: Dialysis
      patients with bacterial endocarditis have poor long-term survival, even in the
      current treatment era, with survival rates changing little in the past 2 decades.
      Additional studies are needed to identify risk-reduction measures and develop
      additional treatment strategies for dialysis patients with endocarditis.

PMID- 15558530
TI  - Access to renal transplantation for minority patients with ESRD in Canada.
AB  - BACKGROUND: The incidence of end-stage renal disease is increasing worldwide.
      Renal transplantation generally is the preferred modality of renal replacement
      therapy; however, in the United States, it is known that minority groups
      experience decreased access to renal transplantation. It is unknown whether
      similar differences exist in Canada. METHODS: Using the Canadian Organ
      Replacement Register, we identified 25,632 Canadian patients 18 years or older
      initiating renal replacement therapy during 1990 to 1998. We used Cox regression
      models to examine adjusted renal transplantation rates among whites, aboriginals,
      blacks, South Asians, and East Indians during an 8-year period. RESULTS: Adjusted
      overall transplantation rates were decreased in comparison to whites for
      aboriginals (rate ratio [RR], 0.54; 95% confidence interval, 0.45 to 0.63),
      blacks (RR, 0.54; 95% confidence interval, 0.46 to 0.66), South Asians (RR, 0.69;
      95% confidence interval, 0.61 to 0.79), and East Indians (RR, 0.66; 95%
      confidence interval, 0.56 to 0.78). Race was at least as strong a predictor of
      transplantation as other known predictors, including age, sex, primary renal
      diagnosis, and comorbidities. Disparities in renal transplantation rates
      increased over time from 1990 to 1998 for all racial groups in comparison to
      whites. CONCLUSION: Renal transplantation rates differ substantially by race in
      Canada, and these differences appear to be worsening over time. Future work
      should focus on identifying the specific barriers responsible for these
      differences in care.

PMID- 15558531
TI  - Effect of surgical banding of a high-flow fistula on access flow and cardiac
      output: intraoperative and long-term measurements.
AB  - Creation of either a natural arteriovenous graft or a fistula as a vascular
      access to support long-term hemodialysis can lead to "high-output" cardiac
      failure. The authors describe a patient who underwent surgical banding of an
      upper arm arteriovenous fistula. Access flow and cardiac output were measured not
      only pre- and postoperatively but also intraoperatively using a modified Swan
      Ganz catheter, originally developed to measure access flows during radiologic
      procedures. Banding resulted in a significant decrease in access flow and cardiac
      output, which was sustained for up to 1 year postoperatively.

PMID- 15558532
TI  - Linezolid disposition after standard dosages in critically ill patients
      undergoing continuous venovenous hemofiltration: a report of 2 cases.
AB  - Linezolid is a new oxazolidinone antibiotic active against most Gram-positive
      microorganisms the renal elimination of which accounts for about 30% to 35% of
      all the clearance. Its pharmacokinetic ability was assessed during continuous
      venovenous hemofiltration (CVVH) in 2 anuric patients with severe postsurgical
      intraabdominal infections who were receiving standard dosages (600 mg
      intravenously twice a day). Blood samples for quantification of linezolid in
      plasma and in filtrate were collected after more than 4 days of therapy before
      dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9, and 11 hours after the morning 1-hour
      intravenous infusion, and concentrations were determined by means of high
      performance liquid chromatography. Linezolid was partially cleared by CVVH in
      both the patients (hemofiltration clearance [CL CVVH ] = 0.38 and 0.35
      mL/min/kg), with high sieving coefficient values (0.76 to 0.92). Efficacious
      plasma exposure for time-dependent antibacterial activity of linezolid, either in
      terms of trough levels above minimum inhibitory concentration (MIC) at which 90%
      of the isolates are inhibited (Cmin >MIC90 ) or of area under the plasma
      concentration time curve to MIC90 ratio (AUC/MIC90 ) >100 hours, was ensured
      during CVVH in both patients. However, despite similar CL CVVH , significant
      interindividual pharmacokinetic variability was found in the 2 patients (AUC
      during the observational period [AUC 0-tau ] 334.71 versus 109.34 mg/L x h),
      mainly owing to substantial differences in non-CVVH-related clearance of
      linezolid (total CL, 0.55 versus 1.21 mL/min/kg). Our findings indicate that
      linezolid, although partially removed, does not warrant dosage modification
      during the first 48 hours when CVVH (with polysulfide hemofilter) at standard
      2,000 mL/h substitution flow rate in predilution is applied to anuric patients.
      Thereafter, this choice is a reasonable one with the exception of those patients
      who have other features of linezolid toxicity and in which non-CVVH-related
      clearance might be impaired, although further evaluations are warranted.

PMID- 15558533
TI  - Renal apolipoprotein A-I amyloidosis associated with a novel mutant Leu64Pro.
AB  - Apolipoprotein A-I amyloidosis (Apo A-I) is an inherited systemic disease that
      results from the pathologic deposition in tissues throughout the body of fibrils
      composed of Apo A-I-related molecules. This disorder has been linked to mutations
      occurring within the coding region of the Apo A-I gene and, to date, 11 such
      substitutions have been documented. In 4 of these cases, the kidney was the
      target organ of the disease process. The authors report their studies on a
      patient with renal amyloidosis and a heretofore undescribed alteration in the
      amyloidogenic precursor protein. Analyses of genomic DNA evidenced a transition
      in the second base of codon 64 (T-->C) in one Apo A-I allele that resulted in the
      replacement of leucine by proline at position 64 (Leu64Pro). Additionally,
      fibrils extracted from the kidney and characterized chemically were found to be
      composed almost exclusively of an approximately 96-residue N-terminal Apo A-I
      fragment that contained the Leu64Pro substitution. These studies have provided
      further evidence for Apo A-I amyloidogenicity and the propensity of certain
      mutants to deposit in renal parenchyma.

PMID- 15558534
TI  - Bone resorption and "relative" immobilization hypercalcemia with prolonged
      continuous renal replacement therapy and citrate anticoagulation.
AB  - Regional citrate anticoagulation is an alternative to heparin in patients with
      bleeding diatheses who require continuous renal replacement therapy (CRRT). The
      short-term metabolic consequences that occur with citrate anticoagulation are
      well described and usually manageable if established protocols are followed
      vigilantly. Because of its customary short-term nature, the long-term
      consequences of CRRT with citrate are less often considered and have not been
      reported. The authors present the case of a woman with multisystem organ failure
      and prolonged acute renal failure who required CRRT for 120 days. Throughout her
      hospital course, adequate regional anticoagulation was achieved by blocking the
      coagulation cascade via the chelation of calcium by citrate. Despite an
      appropriate drop in the postfilter ionized calcium level, by 8 weeks after the
      initiation of CRRT, the patient was able to normalize serum calcium levels
      without the customary calcium infusion. Bone resorption owing to prolonged
      immobilization leading to hypercalcemia is a known complication of critically ill
      patients. This problem is more pronounced in patients with high bone turnover
      rates owing to conditions such as secondary hyperparathyroidism. In this
      particular case, the chelation of calcium by citrate masked the ensuing
      immobilization hypercalcemia, resulting in marked bone loss and bilateral
      spontaneous femoral fractures in the context of normal calcium levels. In
      critically ill patients sustained with prolonged CRRT with citrate
      anticoagulation, bone resorption and "relative" immobilization hypercalcemia may
      manifest as normal serum calcium levels in the face of falling calcium infusion
      rate requirements.

PMID- 15558535
TI  - Exchanging kidneys: how much unfairness is justified by an extra kidney and who
      decides?

PMID- 15558536
TI  - An 80-year-old man with renal insufficiency, proteinuria, hematuria, hemiparesis,
      and pleuritis.

PMID- 15558542
TI  - Characterizing multiple independent behavioral correlates of cell firing in
      freely moving animals.
AB  - The heterogeneous sampling of behavioral states by freely moving animals hinders
      our ability to relate neuronal firing rates to behavioral variables by
      introducing dependencies between them. We specifically consider the animal's
      location and orientation, although our analyses may generalize to other
      behavioral variables, such as speed of movement. A maximum-likelihood approach is
      presented for producing estimates of the separate histograms relating firing rate
      to multiple independent causes. Examples show that the method can be used to
      avoid the artifactual behavioral correlates of place and head direction-cell
      firing produced by standard analyses; to characterize the independent influences
      of both location and orientation in a third cell type (Cacucci et al., 2004); and
      to demonstrate the location-independence of the directional firing of head
      direction cells.

PMID- 15558543
TI  - Hippocampal lesions that abolish spatial maze performance spare object
      recognition memory at delays of up to 48 hours.
AB  - The hippocampus is widely considered to be a critical component of a medial
      temporal lobe memory system, necessary for normal performance on tests of
      declarative memory. Object recognition memory is thought to be a classic test of
      declarative memory function. However, previous tests of the effects of
      hippocampal lesions on object recognition memory have not always supported this
      view. One possible reason for this inconsistency is that previously reported
      effects of hippocampal lesions on object recognition memory tasks may have
      stemmed not from a deficit in object recognition memory per se, but as a result
      of spatial and contextual confounds in the task. Thus, in the present study, we
      used a spontaneous object recognition test in a modified apparatus designed to
      minimize spatial and contextual factors. A group of rats with complete
      excitotoxic lesions of the hippocampus and a group of control rats were tested on
      this modified spontaneous object recognition task with retention delays of up to
      48 h. These rats were also tested on a spatial nonmatching-to-place task. Spatial
      memory performance was abolished following hippocampal lesions, whereas
      performance on the recognition memory task was intact at all delays tested.

PMID- 15558544
TI  - Monitoring congenital rubella embryopathy.
AB  - BACKGROUND: Currently, all developed countries include rubella vaccination in
      their immunization programs, targeting the complete elimination of congenital
      rubella syndrome (CRS). In the underdeveloped world, where this severely
      disabling condition still exists, only a few countries have implemented
      vaccination policies, and almost no data on their effectiveness or on prevalence
      rates are available. The aims of the present work were to search for the best
      phenotype to be used as a sentinel for CRS in a large series of malformed
      newborns and to propose a CRS surveillance system, based only on clinical data.
      METHODS: A total of 43 infants diagnosed as having CRS were obtained from 19,184
      multimalformed infants, ascertained by the Latin-American Collaborative Study of
      Congenital Malformations, World Health Organization (WHO) Collaborating Centre
      for the Prevention of Birth Defects (ECLAMC), over 3,883,165 consecutive births,
      between 1982 and 2003. They were distributed by country and the most frequent
      birth defects were identified. From the 19,184 multimalformed infants, all cases
      presenting the birth defects identified were selected. The sensitivity,
      specificity, and likelihood ratio (LR) in detecting CRS were determined for these
      birth defects, alone and in combination. The sample size of multimalformed
      infants required to detect different levels of increase in the rate of CRS was
      determined for three sentinel phenotypes. RESULTS: The rate of CRS was highest in
      Brazil. Based on the best possible combination of sensitivity, specificity, and
      LR, the dyad comprising eye anomalies and congenital heart defects was shown to
      be the most appropriate sentinel, with the lowest sample size required, to detect
      CRS in neonates. CONCLUSIONS: A surveillance system for CRS, based on clinical
      data in newborns, is being proposed, in an attempt to monitor ongoing vaccination
      policies, aimed at eliminating CRS in developing countries.

PMID- 15558545
TI  - Extent of protein-protein interactions and quasi-equivalence in viral capsids.
AB  - Viral capsids are composed of multiple copies of one or a few gene products that
      self-assemble on their own or in the presence of the viral genome and/or
      auxiliary proteins into closed shells (capsids). We have analyzed 75 high
      resolution virus capsid structures by calculating the average fraction of the
      solvent-accessible surface area of the coat protein subunits buried in the viral
      capsids. This fraction ranges from 0 to 1 and represents a normalized protein
      protein interaction (PPI) index and is a measure of the extent of protein-protein
      interactions. The PPI indices were used to compare the extent of association of
      subunits among different capsids. We further examined the variation of the PPI
      indices as a function of the molecular weight of the coat protein subunit and the
      capsid diameter. Our results suggest that the PPI indices in T=1 and pseudo-T=3
      capsids vary linearly with the molecular weight of the subunit and capsid size.
      This is in contrast to quasi-equivalent capsids with T>or=3, where the extent of
      protein-protein interactions is relatively independent of the subunit and capsid
      sizes. The striking outcome of this analysis is the distinctive clustering of the
      "T=2" capsids, which are distinguished by higher subunit molecular weights and a
      much lower degree of protein-protein interactions. Furthermore, the calculated
      residual (R(sym)) of the fraction buried surface areas of the structurally unique
      subunits in capsids with T>1 was used to calculate the quasi-equivalence of
      different subunit environments.

PMID- 15558546
TI  - Identification of amino acids important for target recognition by the DNA:m5C
      methyltransferase M.NgoPII by alanine-scanning mutagenesis of residues at the
      protein-DNA interface.
AB  - DNA:m(5)C MTases comprise a catalytic domain with conserved residues of the
      active site and a strongly diverged TRD with variable residues involved in DNA
      recognition and binding. To date, crystal structures of 2 DNA:m(5)C MTases
      complexed with the substrate DNA have been obtained; however, for none of these
      enzymes has the importance of the whole set of DNA-binding residues been
      comprehensively studied. We built a comparative model of M.NgoPII, a close
      homologue and isomethylomer of M.HaeIII, and systematically analyzed the effect
      of alanine substitutions for the complete set of amino acid residues from its TRD
      predicted to be important for DNA binding and target recognition. Our data
      demonstrate that only 1 Arg residue is indispensable for the MTase activity in
      vivo and in vitro, and that mutations of only a few other residues cause
      significant reduction of the activity in vitro, with little effect on the
      activity in vivo. The identification of dispensable protein-DNA contacts in the
      wild-type MTase will serve as a platform for exhaustive combinatorial mutagenesis
      aimed at the design of new contacts, and thus construction of enzyme variants
      that retain the activity but exhibit potentially new substrate preferences.

PMID- 15558547
TI  - Challenges in constructing statistically based structure-activity relationship
      models for developmental toxicity.
AB  - Regulatory agencies are increasingly called upon to review large numbers of
      environmental contaminants that have not been characterized for their potential
      to pose a health risk. Additionally, there is special interest in protecting
      potentially sensitive subpopulations and identifying developmental toxicants that
      may be present in the environment. Thus, there is an urgent need for efficient
      methods to screen large numbers of chemicals for their potential to pose a
      developmental hazard. One potential screening method involves the use of
      statistically based structure-activity relationship (SAR) tools to predict
      activity of untested chemicals. Such systems rely on statistical analyses to
      discern relationships between structure and activity for a training set of
      substances. Predictions can then be made for an untested substance as long as its
      structural features are encompassed by chemicals of the training set. In theory,
      such systems could assist regulatory agencies in their screening efforts;
      however, to date, there has been little independent evaluation of these tools for
      this use. To contribute to such an evaluation, the International Life Sciences
      Institute Risk Science Institute (ILSI RSI) convened a Working Group to examine
      methodology used to construct statistically based SAR systems for developmental
      toxicity. This document reports on the deliberations of the Working Group, which
      concluded that an improved process is needed for utilizing developmental toxicity
      data in the construction of statistically based SAR models. The process must be
      objective, reproducible, rational and transparent. Moreover, it must be informed
      by the expertise of developmental toxicologists and biologists and must be
      subject to peer review.

PMID- 15558548
TI  - Vertebral neoplastic compression fractures: assessment by dual-phase chemical
      shift imaging.
AB  - PURPOSE: To compare normal vertebrae with vertebrae with neoplastic compression
      fractures by means of opposed-phase (OP) and in-phase (IP) gradient-echo (GRE)
      imaging. MATERIALS AND METHODS: On OP and IP T1-W GRE images (obtained at 1.5 T
      with the fast low-angle shot (FLASH) technique) of dual-phase chemical shift
      sequences, we compared the signal intensity ratios (SIRs) of normal and
      compression-fractured vertebrae in 108 patients. Dual-phase chemical shift
      sequences were measured in three groups of vertebral bone marrow in terms of the
      relative SIR in OP and IP images: group 1: normal vertebrae (N = 30 with 90
      vertebrae); group 2: non-neoplastic compression-fractured vertebrae (N = 58 with
      73 vertebrae); and group 3: neoplastic compression-fractured vertebrae (N = 20
      with 27 vertebrae). The presence of compressed vertebrae was ascertained based on
      the consensus of two experienced radiologists. The mean SIRs among the three
      groups were compared by means of the Tukey-Kramer test. RESULTS: The mean SIRs of
      the three groups (group 1: 0.46 +/- 0.14; group 2: 0.63 +/- 0.21; and group 3:
      1.02 +/- 0.11) were significantly different according to the Tukey-Kramer test (P
      < 0.01). CONCLUSION: OP and IP T1-W GRE MRI of vertebral SI abnormalities can
      help predict the nature of compression fractures.

PMID- 15558549
TI  - Contribution of diffusion tensor imaging to delineation of gliomas and
      glioblastomas.
AB  - PURPOSE: To determine if the diffusion tensor imaging (DTI) parameters fractional
      anisotropy (FA) and mean diffusivity (MD) can differentiate between accompanying
      edema and tumor cell infiltration of white matter (WM) beyond the tumor edge as
      defined from conventional MRI in low- and high-grade gliomas. MATERIALS AND
      METHODS: We examined 12 patients with high-grade gliomas/glioblastomas and eight
      patients with low-grade gliomas and compared them to 10 patients with
      meningiomas, in which no tumor infiltration is expected. The tumor was defined as
      the enhancing area in glioblastomas and meningiomas and as the area of increased
      T2-signal in low-grade gliomas. FA and MD were measured in the center of the
      tumor and in the adjacent WM. The contralateral WM and internal capsule were used
      as an internal standard. RESULTS: Comparing the WM areas of increased T2-signal
      adjacent to meningiomas and glioblastomas, we saw a trend (without significance)
      towards a reduction of FA, but not of MD, in glioblastomas. We found no changes
      of FA and MD in the WM adjacent to low-grade gliomas (without T2-signal increase)
      compared to the WM of the contralateral hemisphere. In meningiomas and high-grade
      gliomas/glioblastomas, a narrow rim of significantly (P < 0.01) increased FA and
      decreased MD values around the enhancing tumor area was seen, whereas in low
      grade gliomas, such a rim could not be defined. There was no contribution of FA
      or MD to grading of gliomas. CONCLUSION: In glioblastomas, a reduction of FA in
      the edematous area surrounding the tumor may indicate tumor cell infiltration,
      but a reliable differentiation between infiltration and vasogenic edema is not
      yet possible on the basis of DTI. The additional finding of a narrow rim of
      increased FA and decreased MD at the edge of glioblastomas (as well as in
      meningiomas) may be caused by com-pressed WM fibers and/or increased vascularity,
      but does not contribute to exclude peripheral cellular infiltration.

PMID- 15558550
TI  - Relaxation enhancing properties of MnDPDP in human myocardium.
AB  - PURPOSE: To assess magnitude and duration of changes in myocardial longitudinal
      relaxation rate (R1) in humans following infusion of the manganese (Mn) releasing
      contrast agent MnDPDP (Mn-dipyridoxyl-diphosphate). MATERIALS AND METHODS:
      Fifteen healthy volunteers were divided into three groups. After initial
      myocardial and liver R1 measurements using an inversion recovery (IR) turbo fast
      low-angle shot (FLASH) sequence at 1.5 Tesla, the groups were given different
      doses of intravenous MnDPDP: 5, 10 and 15 micromol/kg body weight, respectively,
      over 30 minutes. R1 measurements were then repeated at 1, 2, 4, 8, and 24 hours
      after the infusion ended. RESULTS: The left ventricular wall R1 prevalue was 0.98
      second(-1) (+/-0.04). R1 increased on average (all 15 subjects) 0.41 second(-1)
      (+/-0.09). The increase was present one hour after the end of the infusion,
      remained relatively constant the next two hours, and then declined gradually.
      After 24 hours, there was still a moderate R1 elevation present, with an average
      R1-value of 1.16 (+/-0.05). There were only small differences in myocardial R1
      responses between the three doses investigated, which was contrasted by a marked
      dose-response in liver tissue. CONCLUSION: MnDPDP gave a significant and
      prolonged rise in myocardial R1 even at a dose of 5 micromol/kg. The R1-values in
      the myocardium did not increase linearly with higher doses.

PMID- 15558551
TI  - Spiral phase velocity mapping of left and right coronary artery blood flow:
      correction for through-plane motion using selective fat-only excitation.
AB  - PURPOSE: To develop a method of correcting both right and left coronary artery
      flow velocities for the through-plane motion of the vessel, in order to allow
      details in the temporal flow profiles to be viewed. MATERIALS AND METHODS: The
      methods developed use selective excitation and velocity mapping of the epicardial
      fat surrounding the artery, either in a separate acquisition (temporal resolution
      = 22 msec) or interleaved with the water-excitation acquisition (temporal
      resolution = 44 msec) used to determine coronary blood flow velocities. The two
      methods were compared in 10 right and 13 left coronary arteries in healthy
      volunteers. RESULTS: For the right coronary arteries, correction for through
      plane motion significantly reduces the mean systolic flow velocity (75.3
      mm/second vs. 90.0 mm/second, P < 0.01), while the mean diastolic flow velocity
      is unchanged (96.8 mm/second vs. 94.5 mm/second, P = ns). The resulting profiles
      are biphasic, with approximately equal flow in systole and diastole. For the left
      arteries, correction for through-plane motion reduces the mean systolic flow
      velocity (25.0 mm/second vs. 72.8 mm/second, P < 0.001), resulting in the
      expected diastolic predominant flow profiles. For the right arteries, there were
      no significant differences in the mean systolic and mean diastolic velocities
      after correction with the separate fat-excitation acquisition, and after
      correction the poorer temporal resolution combined water excitation/fat
      excitation acquisition. However, for the left coronary arteries, the combined
      water excitation/fat excitation acquisition resulted in a slight reduction in the
      mean diastolic velocity (121.5 mm/second vs. 130.9 mm/second, P < 0.05).
      CONCLUSION: Selective excitation of the surrounding epicardial fat enables
      through-plane correction of both left and right coronary flow velocities,
      enabling the temporal details of flow velocity to be viewed. With a combined
      WE/FE acquisition, this can be performed without extending the study duration;
      however, the reduced temporal resolution and temporal mismatch of the excitations
      results in a blunting of rapidly changing flow profiles. As such, it may be less
      suitable for the left coronary artery, which has a greater range of through-plane
      motion than the right, and correction using separate WE and FE acquisitions, or
      the adjacent myocardium, may be preferable.

PMID- 15558552
TI  - Impact of lung volume on MR signal intensity changes of the lung parenchyma.
AB  - PURPOSE: To test the hypothesis that, in magnetic resonance (MR) imaging of
      healthy individuals, equal relative changes in lung volume cause equal relative
      changes in MR signal intensity of the lung parenchyma. MATERIALS AND METHODS: In
      two experimental runs, 10 volunteers underwent spirometrically monitored MR
      imaging of the lungs, with MR images acquired at 10 incremental lung volumes
      ranging from total lung capacity to 10% above residual volume. Average signal
      intensity, signal variability, and signal intensity integrals were calculated for
      each volunteer and for each lung volume. The effect of lung volume on signal
      intensity was quantified using linear regression analysis complemented by the
      runs test. Slopes and intercepts of regression lines were compared with an
      analysis of covariance. Slopes of the lines of best fit for lung volumes and
      signal intensities from the two runs were compared to the slope of the line of
      identity. Comparisons between the two runs were visualized using Bland and Altman
      plots. RESULTS: The slopes of the 10 individual regression lines yielded no
      significant differences (F = 1.703, P = 0.101; F = 1.321, P = 0.239). The common
      slopes were -0.556 +/- 0.027 (P = 0.0001) for the first and -0.597 +/- 0.0031 (P
      = 0.0001) for the second experimental run. Both slopes displayed no significant
      nonlinearity (P = 0.419 and P = 0.067). There was a strong association between
      changes in lung volumes (rs = 0.991, P = 0.0001) and changes in signal intensity
      (rs = 0.889, P = 0.0001) in the two experimental runs. Lines of best fit for lung
      volume and signal intensities were not significantly different from the slope of
      the line of identity (P = 0.321 and P = 0.212, respectively). CONCLUSION: Equal
      changes in lung volume cause equal changes in MR signal intensity of the lung
      parenchyma. This linear and reproducible phenomenon could be helpful in comparing
      pulmonary MR signal intensity between individuals.

PMID- 15558553
TI  - The SENSE ghost: field-of-view restrictions for SENSE imaging.
AB  - PURPOSE: To describe a known (but undocumented) limitation in parallel imaging
      using simulation and experiment. This limitation consists of an artifact that
      appears when the imaging field of view (FOV) is less than the object size. This
      study demonstrates this artifact in the phase- and partition-encoding dimensions.
      MATERIALS AND METHODS: One-dimensional simulations as well as in vivo experiments
      were performed with FOVs greater and less than the object being imaged. Full-FOV,
      reduced-FOV, and SENSE reconstructions were visually compared. RESULTS: Image
      artifacts occurred when the final SENSE FOV was smaller than the object being
      imaged. This artifact, termed the SENSE ghost, was a residual fold-over/aliasing
      artifact. Its location was in the central portion of the image rather than at the
      edges of the image. CONCLUSION: This image artifact results from an FOV being
      smaller than the imaged object. The SENSE reconstruction cannot unfold this
      additional fold-over, and will place it in a predictable image location based on
      the SENSE reduction factor. Knowledge of this artifact is necessary when
      prescribing SENSE acquisitions and interpreting the resulting images.

PMID- 15558554
TI  - Estimating haplotype-disease associations with pooled genotype data.
AB  - The genetic dissection of complex human diseases requires large-scale association
      studies which explore the population associations between genetic variants and
      disease phenotypes. DNA pooling can substantially reduce the cost of genotyping
      assays in these studies, and thus enables one to examine a large number of
      genetic variants on a large number of subjects. The availability of pooled
      genotype data instead of individual data poses considerable challenges in the
      statistical inference, especially in the haplotype-based analysis because of
      increased phase uncertainty. Here we present a general likelihood-based approach
      to making inferences about haplotype-disease associations based on possibly
      pooled DNA data. We consider cohort and case-control studies of unrelated
      subjects, and allow arbitrary and unequal pool sizes. The phenotype can be
      discrete or continuous, univariate or multivariate. The effects of haplotypes on
      disease phenotypes are formulated through flexible regression models, which allow
      a variety of genetic hypotheses and gene-environment interactions. We construct
      appropriate likelihood functions for various designs and phenotypes,
      accommodating Hardy-Weinberg disequilibrium. The corresponding maximum likelihood
      estimators are approximately unbiased, normally distributed, and statistically
      efficient. We develop simple and efficient numerical algorithms for calculating
      the maximum likelihood estimators and their variances, and implement these
      algorithms in a freely available computer program. We assess the performance of
      the proposed methods through simulation studies, and provide an application to
      the Finland-United States Investigation of NIDDM Genetics Study. The results show
      that DNA pooling is highly efficient in studying haplotype-disease associations.
      As a by-product, this work provides valid and efficient methods for estimating
      haplotype-disease associations with unpooled DNA samples.

PMID- 15558555
TI  - Microscale multilayer cocultures for biomimetic blood vessels.
AB  - Living tissues have complex and well-organized microstructures. Although
      microtechnology has been used to create in vivo-like cell microstructures in
      vitro, most available microscale systems are two-dimensional, and few three
      dimensional (3D) systems have been explored. This article demonstrates a 3D
      hierarchical biomimetic multilayer microsystem created by a generally applicable
      technique. The technique employs layer-by-layer microfluidics to build layers of
      cells and biopolymers in microchannels, allowing controlled patterning of cells
      and their microenvironments in the x, y, and z-dimension. As a prototype, a
      multilayer system was created using three vascular cell types within
      heterogeneous types of biopolymers to mimic the structure and composition of a
      blood vessel wall. The effects of matrix composition and multilayer
      configurations on 3D cell-cell interactions and cell biology were revealed. Cell
      migration in the z-dimension, matrix remodeling, intercellular adhesion molecule
      expression and actin organization were examined under different 3D coculture
      conditions. A more biomimetic coculture was found to reproduce a more stable
      structure and in vivo-like function. This approach provides a method to fabricate
      microscale hierarchical "neotissues" with 3D configurations of matrix materials
      and multiple cell types, and an in vitro cell coculture model to understand 3D
      processes of cell-cell and cell-matrix interactions.

PMID- 15558556
TI  - Rational discovery of a novel interface for a coactivator in the peroxisome
      proliferator-activated receptor gamma: theoretical implications of impairment in
      type 2 diabetes mellitus.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is important to
      adipocyte differentiation and glucose homeostasis, and mutations in the gene have
      been observed in type 2 diabetes mellitus. The mutated residues, V290 and P467,
      bind to neither ligands nor a coactivator peptide in the reported crystal
      structures of the PPARgamma ligand binding domain. To understand the mechanism of
      type 2 diabetes mellitus caused by germline mutations in the PPARgamma ligand
      binding domain, theoretical models of the PPARgamma-ligand-coactivator complex
      were built at an atomic resolution. In the models, the secondary coactivator
      peptide was docked next to the conventional coactivator peptide, which both
      contain the LXXLL motif. The secondary interface in PPARgamma for the secondary
      coactivator peptide has not been demonstrated by experiments. Binding energy
      calculations of the complex, considering the solvent effect, revealed that the
      secondary coactivator peptide, derived from nuclear receptor box 1 of steroid
      receptor coactivator 1, can be favorably bound to the secondary interface. The
      secondary coactivator peptide forms hydrogen bonds and a hydrophobic core with
      PPARgamma and the primary coactivator peptide. Next, we applied mutations to
      PPARgamma in silico and found that the V290M mutation, observed in type 2
      diabetes mellitus, adversely affected the binding of the secondary peptide. Thus,
      our model provides structural insight into the impairment of PPARgamma function
      in type 2 diabetes mellitus.

PMID- 15558557
TI  - The solution structure of BmTx3B, a member of the scorpion toxin subfamily alpha
      KTx 16.
AB  - This article reports the solution structure of BmTx3B (alpha-KTx16.2), a
      potassium channel blocker belonging to the subfamily alpha-KTx16, purified from
      the venom of the Chinese scorpion Buthus martensi Karsch. In solution, BmTx3B
      assumes a typical CSalphabeta motif, with an alpha-helix connected to a triple
      stranded beta-sheet by 3 disulfide bridges, which belongs to the first structural
      group of short-chain scorpion toxins. On the other hand, BmTx3B is quite
      different from other toxins (such as ChTx and AgTx2) of this group in terms of
      the electrostatic and hydrophobic surface distribution. The functional surface
      (beta-face) of the molecule is characterized by less basic residues (only 2:
      Lys28 and Arg35) and extra aromatic residues (Phe1, Phe9, Trp15, and Tyr37). The
      peptide shows a great preference for the Kca1.1 channel over the Kv channel
      (about a 10(3)-fold difference). The model of BmTx3B/Kca1.1 channel complex
      generated by docking and dynamic simulation reveals that the stable binding
      between the BmTx3B and Kca1.1 channel is favored by a number of aromatic pi-pi
      stacking interactions. The influences of these structural features on the kinetic
      behavior of the toxin binding to Kca1.1 channel are also discussed.

PMID- 15558558
TI  - Dynamic contrast-enhanced MRI of the pancreas: initial results in healthy
      volunteers and patients with chronic pancreatitis.
AB  - PURPOSE: To characterize pancreatic perfusion in volunteers and patients with
      chronic pancreatitis (CP) by dynamic contrast-enhanced (DCE) MRI. MATERIALS AND
      METHODS: Pancreatic enhancement after bolus injection of Gd-DTPA with a three
      dimensional ultrafast partial-Fourier radiofrequency (RF) spoiled gradient-echo
      (GE) acquisition was examined prospectively. An acquisition volume of the
      pancreatic parenchyma was obtained every 4.2 seconds during a single breath-hold
      in 31 volunteers and 19 patients with CP. We calculated the wash-in rate and a
      newly defined parameter, the "time-to-inflow deceleration" (TID). A statistical
      analysis of the differences between both groups was performed with the use of
      Student's t-test. RESULTS: Significant differences in the TID and wash-in rate
      were found for the head and body of the pancreas: the TID was 22.4 sec +/- 4.4
      sec and 23.5 sec +/- 6.1 sec in the pancreatic head and body of the healthy
      volunteers, and 29.8 sec +/- 8.6 sec and 29.4 sec +/- 3.8 sec in patients with
      CP. The wash-in rate was 96 +/- 37 sec(-1) and 101 +/- 27 sec(-1) in controls,
      and 62 +/- 17 sec(-1) and 75 +/- 27 sec(-1) in CP. CONCLUSION: CP can be
      identified by semiquantitative changes on DCE-MRI. Whether DCE-MRI of the
      pancreas can be used to detect early CP remains to be validated.

PMID- 15558559
TI  - Smooth muscle tumors of uncertain malignant potential and leiomyosarcomas of the
      uterus: MR findings.
AB  - PURPOSE: To study the MR characteristics of nonbenign uterine smooth muscle
      tumors. MATERIALS AND METHODS: Nine patients with pathologically proven
      leiomyosarcomas, and three patients with smooth muscle tumors of uncertain
      malignant potential (SMTUMP) were included in this study. Twelve cases of benign
      uterine leiomyomas and variants, in which gynecologists suspected
      leiomyosarcomas, were also analyzed. In each case we studied the size, location,
      signal intensity, and contrast enhancement of the tumors. RESULTS: Nine of the 12
      nonbenign characters had more than 50% of high-intensity areas on T2-weighted
      images (T2WI), and some hyperintense foci on T1-weighted images (T1WI). In the
      contrast study, nine of 12 nonbenign characters had well-demarcated unenhanced
      areas. On the other hand, only two of 12 benign characters showed such a signal
      intensity pattern, and none of them had a pocket-like unenhanced area.
      CONCLUSION: Although there were some exceptions, more than 50% of high signal on
      T2WI, and the presence of any small high-signal areas on T1WI with unenhanced
      pockets were considered MR-suggestive for SMTUMPs and leiomyosarcomas.

PMID- 15558560
TI  - Muscle kinematics during isometric contraction: development of phase contrast and
      spin tag techniques to study healthy and atrophied muscles.
AB  - PURPOSE: To develop and compare phase-contrast (PC) and spin-tag (ST) MR imaging
      techniques for accurate quantification of velocity and displacement distribution
      in the muscle tendon complex of the lower leg during isometric contractions under
      in vivo conditions, in healthy subjects and subjects with atrophy. MATERIALS AND
      METHODS: Techniques were developed to acquire PC and ST dynamic images, gated to
      the force exerted by a subject during isometric contraction. Algorithms were
      optimized for correction of phase shading errors. Flow velocity quantification
      was validated in phantoms and ex vivo rabbit muscles. Trajectories of pixels
      calculated from PC images were compared with those in ST images. Velocity
      distributions were determined in healthy muscles, those atrophied by four weeks
      of suspension, and during physiotherapy-induced recovery. RESULTS: The technique
      developed allowed acquisition of images retrospectively gated to the isometric
      contraction performed with the subject in the scanner. Significant phase shading
      errors in PC images (approximately 3 cm/second over the field of view) were
      reduced to the background noise level by the correction algorithm. Tissue
      trajectories calculated from PC images agreed very well with those from ST images
      both in human and excised animal tissues. Peak velocities in atrophied muscles
      were significantly lower compared to the preatrophy state but recovered to
      baseline values after six weeks of therapy. CONCLUSION: We show the feasibility
      of monitoring muscle velocity and tissue displacement during voluntary
      contractions in humans under in vivo conditions using MR tissue motion mapping
      methods. The clinical feasibility of this technique in monitoring atrophied
      muscle is also demonstrated.

PMID- 15558561
TI  - T2-weighted spine imaging with a fast three-point dixon technique: comparison
      with chemical shift selective fat suppression.
AB  - PURPOSE: To develop a phased-array coil-compatible, fast three-point Dixon (TPD)
      technique, and compare its performance in T2-weighted spine imaging with that of
      the standard chemical shift selective (CHESS) fat suppression technique.
      MATERIALS AND METHODS: We acquired T2-weighted spine images of 27 patients using
      essentially identical scanning parameters with the fast TPD technique and
      standard fast spin echo (FSE) with CHESS fat suppression. A phased-array coil
      compatible image reconstruction algorithm was developed to generate separate
      water and fat images from the data acquired with the fast TPD technique. Three
      neuroradiologists independently scored the images from the two different
      techniques for uniformity of fat suppression and lesion conspicuity using a four
      point system (1 = poor, 2 = fair, 3 = good, 4 = best). RESULTS: The reviewers'
      mean scores were 3.2 and 2.1 for the uniformity of fat suppression, and 3.0 and
      2.0 for the lesion conspicuity for the fast TPD and the CHESS fat suppression
      techniques, respectively. The fast TPD technique was statistically superior to
      the CHESS technique at P < 0.0005. CONCLUSION: The fast TPD technique provides
      superior fat suppression and lesion conspicuity, and potentially can be used as
      an alternative to T2-weighted imaging of the spine.

PMID- 15558562
TI  - Comparative study of FAST gradient echo MRI sequences: phantom study.
AB  - PURPOSE: To investigate a balanced steady state free precession sequence (b-SSFP)
      under a large range of conditions and to compare its performance with other types
      of gradient echo sequences for dynamic imaging. MATERIALS AND METHODS: Balanced
      turbo field echo (b-TFE; Philips Medical Systems, Best, The Netherlands) was
      investigated in vitro at a range of T2/T1 along with T1-contrast enhanced turbo
      field echo (T1-TFE) and turbo field echo (TFE) so that a comparison could be
      made. Performance was quantified in terms of the initial slope of the signal-to
      noise ratio (SNR) vs. 1/T1 curve (sensitivity) and the range of 1/T1 before
      signal saturation (contrast dynamic range [CDR]). RESULTS: The b-TFE sequence was
      found to best perform, in terms of an optimal CDR, with a 90 degrees flip angle
      (FA), saturation preparation, and short inversion time. Using these parameters,
      the sensitivity was also higher than that of the TFE sequence and T1-TFE sequence
      under their respective optimal conditions. For detection of small changes in
      contrast agent concentration (0.0-0.1 mM), b-TFE was also found to be the
      sequence of choice, with optimized parameters as follows, 90 degrees FA, shortest
      TR/TE, and no magnetization preparation. The smallest matrices gave the highest
      signal sensitivity for all three sequences. CONCLUSION: The CDR of b-TFE was much
      narrower than that of T1-TFE but could be widened under optimized conditions. The
      sensitivity of the b-TFE technique was the highest of the three sequences under
      all conditions tested.

PMID- 15558563
TI  - Neurochemistry of late-life major depression: a pilot two-dimensional MR
      spectroscopic study.
AB  - PURPOSE: To evaluate a two-dimensional localized chemical shift correlated
      spectroscopy (L-COSY) sequence in elderly patients with major depression.
      MATERIALS AND METHODS: A total of 33 healthy elderly subjects and 15 elderly
      patients with major depression were investigated. A voxel size of 3 x 3 x 3 cm3
      was chosen in the dorsolateral prefrontal region with predominantly white matter,
      with the use of three slice-selective radiofrequency (RF) pulses (90 degrees ,
      180 degrees , and 90 degrees). A chemical shift-selective (CHESS) sequence was
      used prior to volume localization for the presaturation of water. The two
      dimensional raw data matrix consisted of 1024 complex points along the detection
      period (t2), and 100 increments along the evolution period (t1), resulting in a
      total acquisition time of approximately 27 minutes per acquisition. The
      metabolite ratios were calculated using the two-dimensional peak volumes with
      respect to the diagonal peak volume of total creatine (Cr) at 3.0 ppm. RESULTS:
      In the 33 elderly subjects, the mean ratio of choline (Cho) to Cr was 10% higher
      in men compared to women (P < 0.05), consistent with earlier findings obtained by
      one-dimensional MRS. When the metabolite ratios were compared in a subsample of
      16 elderly female controls and 12 depressed female patients, the depressed
      geriatric patients had higher levels of myoinositol (mI), phosphoethanolamine
      (PE), and glutamate/glutamine (Glx) than the controls, although the differences
      were not statistically significant. CONCLUSION: Our pilot study shows the
      feasibility of performing two-dimensional L-COSY successfully in elderly subjects
      and patients with late-life mood disorders. These findings are consistent with
      and expand on our earlier findings in major depressive disorder (MDD) detected
      with one-dimensional MRS.

PMID- 15558564
TI  - Marker of parasitic cysts on in vivo proton magnetic resonance spectroscopy: is
      it succinate or pyruvate?

PMID- 15558565
TI  - Crystal structure of PH0010 from Pyrococcus horikoshii, which is highly
      homologous to human AMMECR 1C-terminal region.

PMID- 15558566
TI  - Structural evidence for variable oligomerization of the N-terminal domain of
      cyclase-associated protein (CAP).
AB  - Cyclase-associated protein (CAP) is a highly conserved and widely distributed
      protein that links the nutritional response signaling to cytoskeleton remodeling.
      In yeast, CAP is a component of the adenylyl cyclase complex and helps to
      activate the Ras-mediated catalytic cycle of the cyclase. While the N-terminal
      domain of CAP (N-CAP) provides a binding site for adenylyl cyclase, the C
      terminal domain (C-CAP) possesses actin binding activity. Our attempts to
      crystallize full-length recombinant CAP from Dictyostelium discoideum resulted in
      growth of orthorhombic crystals containing only the N-terminal domain (residues
      42-227) due to auto-proteolytic cleavage. The structure was solved by molecular
      replacement with data at 2.2 A resolution. The present crystal structure allows
      the characterization of a head-to-tail N-CAP dimer in the asymmetric unit and a
      crystallographic side-to-side dimer. Comparison with previously published
      structures of N-CAP reveals variable modes of dimerization of this domain, but
      the presence of a common interface for the side-to-side dimer.

PMID- 15558567
TI  - Stroke patients' evolving symptoms assessed by tractography.
AB  - PURPOSE: To test the hypothesis that an interval evolution in the location of the
      depicted sensorimotor tract relative to the infarct (the "tract-infarct
      relationship") may be related to stroke victims' symptom progression. MATERIALS
      AND METHODS: Patients (N = 7) who underwent multiple diffusion-tensor imaging
      (DTI) studies during symptomatic progression were included in this study. DTI was
      performed using a single-shot echo-planar imaging (EPI) technique with a motion
      probing gradient in six orientations, a b-value of 800 seconds/mm2, and six image
      averages. The total scan time was four minutes and 24 seconds. Fiber-tracking of
      the sensorimotor pathways was performed, and the locations of these tracts were
      retrospectively assessed in relation to the evolution of the symptoms. RESULTS:
      Five of the seven patients showed an interval enlargement of the infarct on
      diffusion-weighted (DW) images. In two of these cases the lesion enlarged to
      involve the sensorimotor tracts, while in three cases the lesion enlarged only so
      far to come into close proximity to the sensorimotor tract. In the remaining two
      cases there was no interval enlargement of the infarct, and therefore the tract
      infarct relationship could not account for the evolution of the symptoms in these
      cases. CONCLUSION: A tract-infarct relationship can be observed with the use of a
      fiber-tracking technique, and the results may improve our understanding of the
      symptom progression seen in stroke victims.

PMID- 15558568
TI  - New joint covariance- and marginal-based tests for association and linkage for
      quantitative traits for random and non-random sampling.
AB  - We develop novel statistical tests for transmission disequilibrium testing (tests
      of linkage in the presence of association) for quantitative traits using parents
      and offspring. These joint tests utilize information in both the covariance (or
      more generally, dependency) between genotype and phenotype and the marginal
      distribution of genotype. Using computer simulation we test the validity (Type I
      error rate control) and power of the proposed methods, for additive, dominant,
      and recessive modes of inheritance, locus-specific heritability of the trait
      0.05, 0.1, 0.2 with allele frequencies of P=0.2 and 0.4, and sample sizes of 500,
      200, and 100 trios. Both random sampling and extreme sampling schemes were
      investigated. A multinomial logistic joint test provides the highest overall
      power irrespective of sample size, allele frequency, heritability, and modes of
      inheritance.

PMID- 15558569
TI  - Intraflagellar transport and the flagellar tip complex.
AB  - Intraflagellar transport (IFT) is the term that refers to the microtubule
      dependent particle motility that is common to almost all flagella and cilia and
      is distinct from the mechanism of flagellar beating. IFT involves the rapid, bi
      directional transport of molecular motors and their cargo proteins from the base
      to the tip of the flagellum and back again. While the basic mechanism of IFT is
      well established, the varied functions of this process are continually being
      elucidated. For example, although IFT plays a clear role in flagellar assembly,
      disassembly and stability, the exact sequence of events that take place when
      tubulin subunit addition and loss occur during flagellar assembly and
      disassembly, respectively, are unknown. Key to furthering our understanding of
      IFT is greater knowledge of the flagellar tip complex (FTC) because it is at the
      FTC that flagellar assembly and disassembly, cargo loading and unloading, and
      motor protein regulation occur. Yet these related processes may only represent
      one aspect of the importance of IFT in flagellar dynamics. IFT may also provide
      the basic elements of a signal transduction mechanism that functions to provide
      the nucleus with information about the outside environment and even about the
      state of the flagellum itself. Thus, IFT may function as the central component of
      a signal transduction system that controls flagellar gene transcription.

PMID- 15558570
TI  - Quantitative cerebral perfusion using the PRESTO acquisition scheme.
AB  - PURPOSE: To evaluate the feasibility of using the rapid principles of echo
      shifting with a train of observations (PRESTO) sequence for measurements of
      cerebral hemodynamic parameters based on first pass of a contrast agent.
      MATERIALS AND METHODS: Simulations were performed to investigate potential
      resolution loss due to relaxation effects. Experimental evaluation was conducted
      in healthy monkey brains using PRESTO and echo-planar imaging (EPI). RESULTS: For
      short echo trains, an insignificant contribution of the longitudinal and
      transversal relaxation rates to the signal amplitude in white matter and gray
      matter was found, whereas a contribution as large as 40% was found in large
      vessels. Simulations of the point spread function demonstrated that PRESTO,
      despite its shorter readout trains, only has a small advantage in terms of
      maintenance of image resolution during bolus passage compared to EPI as long as
      the EPI echo train can be kept similar to the T2* value at the top of the bolus.
      Experimental studies revealed that the PRESTO and EPI gray matter to white matter
      ratio were similar with respect to cerebral blood flow (CBF), cerebral blood
      volume (CBV), and mean transit time (MTT). CONCLUSION: The study showed that
      PRESTO and EPI led to comparable quantitative perfusion parameters.

PMID- 15558571
TI  - High-resolution, multicontrast three-dimensional-MRI characterizes
      atherosclerotic plaque composition in ApoE-/- mice ex vivo.
AB  - PURPOSE: To systematically investigate intrinsic MR contrast mechanisms that
      would facilitate plaque characterization and quantification in the aortic root
      and brachiocephalic artery of ApoE-/- mice ex vivo. MATERIALS AND METHODS: To
      establish unambiguous MR parameters for routinely analyzing atherosclerotic
      plaque ex vivo at 11.7 T, relaxation times of plaque components were
      quantitatively assessed. Magnetization transfer and lipid-proton three
      dimensional MR imaging was investigated for visualization of collagen- and lipid
      rich plaque regions, respectively. A three-dimensional multiecho sequence with a
      spatial resolution of 47 x 47 x 63 microm was implemented providing a variable
      degree of T2-weighting. RESULTS: Relaxation time measurements showed clear tissue
      heterogeneity between atherosclerotic plaque components in the T2-values, but
      similar T1-values at 11.7 T (T1/T2 mean +/- SD; cellular plaque component: 1.2 +/
      0.3 seconds/26.3 +/- 0.4 msec; fibrofatty plaque component: 1.1 +/- 0.2
      seconds/13.7 +/- 2.0 msec). The three-dimensional multiecho sequence allowed the
      calculation of the intrinsic proton density and T2-maps. The sum of the multiecho
      data provided strong T2-weighting that facilitated quantification of various
      components of atherosclerotic plaque in the mouse aortic root and correlated well
      with histology (P < 0.0001). CONCLUSION: High-resolution MRI allows for accurate
      classification and quantification of atherosclerotic plaque components in the
      aortic root of mice.

PMID- 15558572
TI  - Improving the prediction of final infarct size in acute stroke with bolus delay
      corrected perfusion MRI measures.
AB  - PURPOSE: To investigate whether bolus delay-corrected dynamic susceptibility
      contrast (DSC) perfusion MRI measures allowed a more accurate estimation of
      eventual infarct volume in 14 acute stroke patients using a predictive tissue
      classifier algorithm. MATERIALS AND METHODS: Tissue classification was performed
      using a expectation maximization and k-means clustering algorithm utilizing
      diffusion and T2 measures (diffusion-weighted imaging [DWI], apparent diffusion
      coefficient [ADC], and T2) combined with uncorrected perfusion measures cerebral
      blood flow ((CBF) and mean transit time [MTT]), bolus delay-corrected perfusion
      measures (cCBF and cMTT), and bolus delay-corrected perfusion indices (cCBF and
      cMTT with bolus delay). RESULTS: The mean similarity index (SI), a kappa-based
      correlation statistic reflecting the pixel-by-pixel classification agreement
      between predicted and 30-day T2 lesion volumes, were 0.55 +/- 0.19, 0.61 +/- 0.15
      (P < 0.02) and 0.60 +/- 0.17 (P <0.03), respectively. Spearman's correlation
      coefficients, comparing predicted and final lesion volumes were 0.56 (P < 0.05),
      0.70 (P < 0.01), and 0.84 (P < 0.001), respectively. We found a more significant
      correlation between predicted infarct volumes derived from bolus delay-corrected
      perfusion measures than from conventional perfusion measures when combined with
      diffusion measures and compared with final lesion volumes measured on 30-day T2
      MRI scans. CONCLUSION: Bolus delay-corrected perfusion measures enable an
      improved prediction of infarct evolution and evaluation of the hemodynamic status
      of neuronal tissue in acute stroke.

PMID- 15558573
TI  - Near-infrared fluorescence imaging and histology confirm anomalous edematous
      signal distribution detected in the rat lung by MRI after allergen challenge.
AB  - PURPOSE: To address the issue concerning the predominant location, on the left
      anatomic side, of edematous signals detected by magnetic resonance imaging (MRI)
      in the lungs of actively sensitized rats following intratracheal (IT) allergen
      challenge. MATERIALS AND METHODS: Near-infrared fluorescence (NIRF) imaging was
      used to detect the lobular distribution in the lungs of normal rats of an IT
      instilled fluorescent dye, Cy5.5. Actively sensitized Brown Norway rats were
      examined by MRI 24 hours after IT administration of ovalbumin. The perivascular
      edema was quantified by histology in the different lobes of lungs removed from
      the same animals immediately after the MRI acquisitions. RESULTS: An uneven
      distribution of Cy5.5 was found, predominantly on the left lobe, paralleling the
      localized development of allergic pulmonary inflammation in the left lobe
      detected as edematous signal by MRI and confirmed by histology. The patterns of
      the distributions of the dye between and within the lobes were very similar to
      those of perivascular edema assessed histologically. CONCLUSION: The data
      indicate a relationship between the molecular deposition of the dye detected by
      NIRF in the lungs and the distribution of allergen eliciting the development of
      pulmonary inflammation in actively rats. The combination of MRI with NIRF imaging
      may provide important information in preclinical pharmacologic research in the
      area of airway diseases. While MRI is able to address the effects of compounds on
      the inflammatory response in models of airways diseases, NIRF imaging may provide
      important insights on drug distribution and interaction in the lung, being thus
      suited for molecular imaging studies.

PMID- 15558574
TI  - Three-dimensional MR angiography in imaging platinum alloy stents.
AB  - PURPOSE: To evaluate visualization inside platinum stents with three-dimensional
      contrast-enhanced magnetic resonance angiography (CE-MRA). MATERIALS AND METHODS:
      Breath-hold three-dimensional gadolinium (Gd) MRA was performed on 18 patients
      with 22 platinum stents in the renal (n = 18), celiac (n = 1), superior
      mesenteric (n = 1), and iliac (n = 2) arteries. Electronic calibers were used to
      measure the lumen diameter within the stent and just distal to the stent to
      calculate percent stenosis. MRA accuracy was determined from the difference
      between percent stenosis measured on MRA and digital subtracted angiography
      (DSA). The patients were imaged at flip angles of 45 degrees , 60 degrees , 75
      degrees , 90 degrees , and 150 degrees . RESULTS: MRA demonstrated the stent
      lumen in all of the patients, with a mean difference between MRA and DSA of 21%.
      For stents oriented parallel to B0 (iliac arteries) the difference was only 10%,
      as compared to 22% for stents perpendicular to B0. The flip angle with the best
      agreement between MRA and DSA was 75 degrees (16%). CONCLUSION: The lumen of a
      platinum stent can be imaged with three-dimensional CE-MRA, although grading of
      restenosis has limited accuracy. The best results were obtained with a flip angle
      of 75 degrees and for stents in the iliac arteries parallel to B0.

PMID- 15558575
TI  - Analysis of pH-dependent elements in proteins: geometry and properties of pairs
      of hydrogen-bonded carboxylic acid side-chains.
AB  - A rather frequent but so far little discussed observation is that pairs of
      carboxylic acid side-chains in proteins can share a proton in a hydrogen bond. In
      the present article, quantum chemical calculations of simple model systems for
      carboxyl-carboxylate interactions are compared with structural observations from
      proteins. A detailed structural analysis of the proteins deposited in the PDB
      revealed that, in a subset of proteins sharing less than 90% sequence identity,
      19% (314) contain at least one pair of carboxylic acids with their side-chain
      oxygen atoms within hydrogen-bonding distance. As the distance between those
      interacting oxygen atoms is frequently very short ( approximately 2.55 A), many
      of these carboxylic acids are suggested to share a proton in a strong hydrogen
      bond. When situated in an appropriate structural environment (low dielectric
      constant), some might even form a low barrier hydrogen bond. The quantum chemical
      studies show that the most frequent geometric features of carboxyl-carboxylate
      pairs found in proteins, and no or symmetric ligation, are also the most stable
      arrangements at low dielectric constants, and they also suggest at medium and low
      pH a higher stability than for isosteric amide-carboxylate pairs. The presence of
      these pairs in 119 different enzymes found in the BRENDA database is set in
      relation to their properties and functions. This analysis shows that pH optima of
      enzymes with carboxyl-carboxylate pairs are shifted to lower than average values,
      whereas temperature optima seem to be increased. The described structural
      principles can be used as guidelines for rational protein design (e.g., in order
      to improve pH or temperature stability).

PMID- 15558576
TI  - Comparison of statistical methods for analysis of clustered binary observations.
AB  - When correlated observations are obtained in a randomized controlled trial, the
      assumption of independence among observations within cluster likely will not hold
      because the observations share the same cluster (e.g. clinic, physician, or
      subject). Further, the outcome measurements of interest are often binary. The
      objective of this paper is to compare the performance of four statistical methods
      for analysis of clustered binary observations: namely (1) full likelihood method;
      (2) penalized quasi-likelihood method; (3) generalized estimating equation
      method; (4) fixed-effects logistic regression method. The first three methods
      take correlations into account in inferential processes whereas the last method
      does not. Type I error rate, power, bias, and standard error are compared across
      the four statistical methods through computer simulations under varying effect
      sizes, intraclass correlation coefficients, number of clusters, and number of
      observations per cluster, including large numbers 20 and 100 of observations per
      cluster. The results show that the performance of the full likelihood and the
      penalized quasi-likelihood methods is superior for analysis of clustered binary
      observations, and is not necessarily inferior to that of the fixed-effects
      logistic regression fit even when within-cluster correlations are zero.

PMID- 15558578
TI  - Assessment of brain tumor angiogenesis inhibitors using perfusion magnetic
      resonance imaging: quality and analysis results of a phase I trial.
AB  - PURPOSE: To determine thresholds of quality for a T2*-weighted perfusion magnetic
      resonance imaging (MRI) study and evaluate the effects of an angiogenesis
      inhibitor on relative blood flow and volume changes in brain tumor patients in a
      multi-institution setting. MATERIALS AND METHODS: A total of 36 volunteers from
      four participating institutions with clinically diagnosed malignant gliomas were
      studied using perfusion MRI protocols. These included a baseline study and follow
      up studies every eight weeks to evaluate the effect of an anti-angiogenic agent
      on tumor perfusion. Quality tests were performed on the perfusion imaging data by
      defining statistical thresholds of acceptance. Region of interest (ROI) analysis
      was performed on tumors and kinetic parameters were normalized with respect to
      normal tissue. RESULTS: Statistical thresholds for goodness of the gamma variate
      fit, T2* recovery, and mean signal full-width half-minimum (FWHMin) were computed
      for our data sets with a 99% one-sided confidence interval; these were 6.91%,
      79.48%, and 23.35 seconds, respectively. Decreases in-blood volume and flow
      measurements were observed in patients with documented clinical response.
      CONCLUSION: Malignant brain tumors have altered perfusion parameters that may be
      used to understand and monitor neovascularization. This permits non-invasive
      assessment of the efficacy of angiogenesis inhibiting drugs.

PMID- 15558579
TI  - A newly recognized syndrome involving limbs, pelvis, and genital organs or a
      variant of Al-Awadi/Raas-Rothschild syndrome?
AB  - We report on a 3-year-old Thai boy with limb, pelvic, and genital malformations.
      The combination of findings found in this patient is similar to that of Al
      Awadi/Raas-Rothchild syndrome (AARRS) or limb/pelvis hypoplasia/aplasia syndrome.
      The upper limbs are more severely affected than the lower ones. Unlike that of
      AARRS, the radial ray is more severely affected than the ulnar ray. The presence
      of humeroulnar synostosis and humero-ulnar-radial synostosis and the absence of a
      radius distinguishes it from AARRS. The similarities and dissimilarities between
      the features in the present patient and other limb-pelvic hypoplasia/aplasia
      syndromes are discussed. The findings in this group of patients appear to
      demonstrate limb-pelvis-genital organ developmental field defects.

PMID- 15558580
TI  - Statistical methods for multivariate interval-censored recurrent events.
AB  - Multi-type recurrent event data arise when two or more different kinds of events
      may occur repeatedly over a period of observation. The scientific objectives in
      such settings are often to describe features of the marginal processes and to
      study the association between the different types of events. Interval-censored
      multi-type recurrent event data arise when the precise event times are
      unobserved, but intervals are available during which the events are known to have
      occurred. This type of data is common in studies of patients with advanced
      cancer, for example, where the events may represent the development of different
      types of metastatic lesions which are only detectable by conducting bone scans of
      the entire skeleton. In this setting it is of interest to characterize the
      incidence of the various types of bone lesions, to estimate the impact of
      treatment and other covariate effects on the development of new lesions, and to
      understand the relationship between the processes generating the bone lesions. We
      develop joint models for multi-type interval-censored recurrent events which
      accommodate dependencies between different types of events and enable one to
      examine the covariate effects via regression. However, since the marginal
      likelihood resulting from the multivariate random effect model is intractable, we
      describe a Gibbs sampling algorithm to facilitate model fitting and inference. We
      use generalized estimating equations for estimation and inference based on
      marginal models. The finite sample properties of the marginal approach are
      studied via simulation. The estimates of both the regression coefficients and the
      variance-covariance parameters are shown to have negligible bias and 95 per cent
      confidence intervals based on the asymptotic variance formula are shown to have
      excellent empirical coverage probabilities in all of the settings considered. The
      application of these methods to data from a trial of women with advanced breast
      cancer provides insight into the clinical course of bone metastases in this
      population.

PMID- 15558581
TI  - Crystal structure of the Co-chaperonin Cpn10 from Thermus thermophilus HB8.

PMID- 15558582
TI  - The pitfall of the cystic duct biliary anastomosis in right lobe living donor
      liver transplantation.

PMID- 15558583
TI  - Structural classification of thioredoxin-like fold proteins.
AB  - Protein structure classification is necessary to comprehend the rapidly growing
      structural data for better understanding of protein evolution and sequence
      structure-function relationships. Thioredoxins are important proteins that
      ubiquitously regulate cellular redox status and various other crucial functions.
      We define the thioredoxin-like fold using the structure consensus of thioredoxin
      homologs and consider all circular permutations of the fold. The search for
      thioredoxin-like fold proteins in the PDB database identified 723 protein
      domains. These domains are grouped into eleven evolutionary families based on
      combined sequence, structural, and functional evidence. Analysis of the protein
      ligand structure complexes reveals two major active site locations for the
      thioredoxin-like proteins. Comparison to existing structure classifications
      reveals that our thioredoxin-like fold group is broader and more inclusive,
      unifying proteins from five SCOP folds, five CATH topologies and seven DALI
      domain dictionary globular folding topologies. Considering these structurally
      similar domains together sheds new light on the relationships between sequence,
      structure, function and evolution of thioredoxins.

PMID- 15558584
TI  - Steroid withdrawal at day 14 after liver transplantation: a double-blind, placebo
      controlled study.
AB  - Some clinical studies in liver transplantation have recently reported safety
      advantages and similar acute rejection rates with early steroid withdrawal. The
      aim of this study was to evaluate the efficacy and safety of an immunosuppressive
      regimen with steroid withdrawal at day 14. A multicenter, 1-year, comparative,
      double blind, placebo-controlled study was performed. Patients undergoing a first
      cadaveric liver transplantation were recruited and all received basiliximab +
      cyclosporine + intravenous methylprednisolone. Patients without severe
      postoperative complications were randomized at day 7 to receive a maintenance
      regimen with Neoral (cyclosporine) + prednisolone (group 1) or without steroids
      (Neoral + placebo; group 2), after a 7-day blinded oral steroid tapering period.
      A total of 174 patients were randomized at day 7 (group 1: n = 90; group 2: n =
      84). The incidence of biopsy-confirmed and treated acute rejection at 6 months
      was 38.1% in group 2 vs. 24.4% in group 1 (P = .03) with a trend for a higher
      incidence of Grade II / III acute rejection (28.6% vs. 18.9%; P = .12). Changes
      from baseline were similar with regard to metabolic parameters (glycemia, total
      cholesterol, and triglycerides). A trend toward a better glucose tolerance was
      observed, as fewer patients received an antidiabetic treatment in the placebo
      group (2 vs. 10). In conclusion, this first double-blind, placebo-controlled
      study of steroid withdrawal at day 14 showed a higher incidence of acute
      rejection, only balanced by a trend of a lower need of antidiabetic treatment.

PMID- 15558585
TI  - Predictors of survival after liver transplantation for hepatocellular carcinoma
      associated with Hepatitis C.
AB  - The efficacy of orthotopic liver transplantation (OLT) for hepatocellular
      carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This
      study examines the variables that may determine the outcome of OLT for HCC in HCV
      patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these
      patients, 67 with concurrent HCC were included in the study. Univariate and
      multivariate analyses considered the following variables: gender, pTNM stage,
      tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant
      chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor
      marker, lobar distribution, and histological grade. Overall OLT survival of HCV
      patients diagnosed with concomitant HCC was significantly lower when compared to
      patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55%
      versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients
      with stage I HCC was significantly better than patients with stage II, III, or IV
      (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence
      included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67
      patients (36%) died during the follow-up time. Causes of deaths included
      recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients
      (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV
      or HCC. Both univariate and multivariate analysis demonstrated that pTNM status
      (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for
      patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM
      staging (P = .038) increased risk of recurrence. Multivariate analysis showed
      that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of
      death after OLT in HCC recipients. In conclusion, this study demonstrates the
      effectiveness of OLT for patients with HCC in a large cohort of chronic HCV
      patients. Advanced tumor stage, and particularly vascular invasion, are poor
      prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant
      chemotherapy, and preoperative chemoembolization were associated with positive
      outcomes for patients who underwent OLT for concomitant HCV and HCC.

PMID- 15558586
TI  - Retransplantation for hepatitis C: what do we really know?

PMID- 15558587
TI  - Determination of the optimal model for end-stage liver disease score in patients
      with small hepatocellular carcinoma undergoing loco-regional therapy.
AB  - The model for end-stage liver disease (MELD) has been a prevailing system to
      prioritize cirrhotic patients awaiting liver transplantation. An "exceptional"
      MELD score of 20 and 24 points is assigned for stage T1 and T2 patients with
      small hepatocellular carcinoma (HCC), respectively. However, this strategy is
      based on scarce data and the optimal score for these patients remains uncertain.
      We investigated 238 patients with small HCC who were candidates for liver
      transplantation and underwent arterial chemoembolization or percutaneous
      injection therapy using acetic acid or ethanol. Tumor stage (P = .001) and Child
      Turcotte-Pugh (CTP) class (P < .001) were independent risk factors predicting
      tumor progression or death in survival analysis. The risk of disease progression
      in HCC patients stratified by tumor stage was mapped and equated with the risk of
      mortality of 456 cirrhotic patients without HCC. The 6- and 12-month rates of
      disease progression were 4% and 6%, respectively, for stage T1 HCC patients (n =
      50; mean MELD: 9.5). These rates were close to and no higher than the mortality
      rate in MELD category 8-12 at the corresponding time period (7.1% and 11.3%,
      respectively; n = 141). For stage T2 patients (n = 188; mean MELD: 9.3), the
      corresponding rates were 5.3% and 13.8%, respectively, which were close to and no
      higher than the mortality rate in MELD category 10-14 (9.0% and 13.9%,
      respectively, n = 166). In conclusion, the risk of disease progression is quite
      low for selected HCC patients undergoing loco-regional therapy. A lower MELD
      score may be suggested to be equivalent to the risk of short- and mid-term
      mortality in the cirrhosis group.

PMID- 15558588
TI  - The transplanted liver graft is capable of clearing asymmetric dimethylarginine.
AB  - Asymmetric dimethylarginine (ADMA) has been recognized as an endogenous inhibitor
      of the arginine-nitric oxide (NO) pathway. Its concentration is tightly regulated
      by urinary excretion and degradation by the enzyme dimethylarginine
      dimethylaminohydrolase (DDAH), which is highly expressed in the liver.
      Considering the liver as a crucial organ in the clearing of ADMA, we hypothesized
      increased ADMA levels during hepatic failure and, consequently, a decline of ADMA
      concentrations after successful liver transplantation. The aim of the present
      study was to investigate the role of the liver in the metabolism of ADMA in
      patients undergoing liver transplantation. In this prospective study, we
      investigated the course of ADMA concentrations in 42 patients undergoing liver
      transplantation and results showed that preoperative ADMA concentrations were
      higher in patients with acute (1.26 micromol/L, P < .001) and in patients with
      chronic (.69 micromol/L, P < .001) hepatic failure compared with healthy
      volunteers (.41 micromol/L). In addition, ADMA concentrations decreased from the
      preoperative day to the first postoperative day in both the acute (Delta(ADMA): 
      .63 micromol/L, P = .005) and the chronic hepatic failure group (Delta(ADMA): 
      0.15 micromol/L, P < .001). Furthermore, in patients who experienced acute
      rejection, ADMA concentrations were higher during the whole first postoperative
      month compared with nonrejectors (P = .012). Moreover, in 11 of 13 rejectors
      (85%) a clear increase in ADMA concentration preceded the onset of the first
      episode of rejection, which was confirmed by liver biopsy. In conclusion, our
      results indicate that the transplanted liver graft is quickly capable of clearing
      ADMA, suggesting preservation of DDAH. In addition, increased ADMA concentrations
      in the posttransplantation period reflect serious dysfunction of the liver graft
      during acute rejection.

PMID- 15558589
TI  - Resolution of alcoholic neuropathy following liver transplantation.
AB  - Between 10 and 20% of adult liver transplants are performed for end-stage
      alcoholic liver disease. Severe extrahepatic end-organ damage from alcoholism
      (cardiomyopathy, pancreatitis, central nervous system injury, and neuropathy) is
      widely regarded as an absolute contraindication to liver transplantation, despite
      a lack of data on the effect of transplantation on these complications. We
      describe such a patient who presented with decompensated alcoholic liver disease
      and moderately severe peripheral neuropathy. Both his liver failure and
      neuropathy progressed despite 9 months abstinence and intensive nutritional
      support. By 12 months post-transplant, however, this patient had regained almost
      normal muscle strength, with associated recovery in sensory and motor conduction
      velocities. Direct alcohol toxicity, nutritional and vitamin deficiencies, and
      liver failure were all likely etiologic factors in this patient's neuropathy. In
      conclusion, this case suggests that peripheral neuropathy in a patient with
      alcoholic cirrhosis may resolve following liver transplantation and should not
      constitute a contraindication to transplantation, even when it is disabling.

PMID- 15558590
TI  - Cardiac morbidity and mortality related to orthotopic liver transplantation.
AB  - This article briefly discusses the cardiac status of liver transplant recipients
      and their preoperative cardiac evaluation. It describes in detail perioperative
      and early and late postoperative complications as well as the cardiac problems
      associated with immunosuppression. The preoperative cardiovascular status of
      patients is important in determining how they cope with the stresses imposed by
      liver transplantation. Minor early cardiac events are common and may influence
      longer term cardiac morbidity. Immunosuppressive therapy may have short term
      effects but is likely to adversely affect long term cardiac risk.

PMID- 15558591
TI  - T-cell receptor Vbeta gene usage in CSF lymphocytes in X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder with impaired very
      long-chain fatty acid (VLCFA) metabolism that produces a neurological disease
      with significant variability of clinical phenotypes even within kindred. The two
      most common forms are the cerebral form (CALD) with an important inflammatory
      reaction at the active edge of demyelinating lesions, resembling some aspects of
      multiple sclerosis pathology, and adrenomyeloneuropathy (AMN), which involves the
      spinal cord and in which the inflammatory reaction is mild or absent. One
      hypothesis is that the phenotypic variability is related to T cell-mediated
      immune mechanisms playing a primary role in the demyelinating pathogenic process
      of CALD. The present study aims to test the hypothesis that CSF of patients with
      the CALD form contains highly restricted T cell populations. The variable regions
      of the T cell receptor beta chains (TCR Vbeta) were studied in CSF from 29 ALD
      patients with different phenotypes. RNA was extracted and cDNA synthesized from
      CSF lymphocytes; TCR Vbeta gene segments were amplified from the cDNA by
      polymerase chain reaction (PCR) using 20 family-specific primers. PCR products
      were analyzed by Southern blot. Some amplified Vbeta products were sequenced. The
      majority of ALD patients (21/29), whatever their phenotype, exhibited oligoclonal
      T cell expansion. However the overexpression of some TCR Vbeta families was
      heterogeneous among the different patients without any preponderance of specific
      Vbeta families or any clustering according to clinical phenotype. In particular a
      dominant TCR Vbeta utilization was not found in patients with CALD.

PMID- 15558592
TI  - Statistical correlation between cell adhesion and proliferation on biocompatible
      metallic materials.
AB  - Our ambition for several years is to appreciate and quantify the long-term
      adhesion of cells on materials at times where the interface between cells and
      substrate becomes more complex, more closed to the cell/matrix/substrate
      interface existing in vivo. With this objective, we quantified the long-term
      adhesion and proliferation of human osteoblasts cultured from 24 h to 21 days on
      pure titanium, titanium alloy, and stainless-steel substrates presenting six
      different surface morphologies and two different roughness amplitude. Hence, we
      did proceed to the statistical correlation of cell adhesion and cell
      proliferation on 30 different substrates. Additionally, we described surface
      topography not only by the roughness amplitude but also by the roughness
      morphology using new specific parameters. By multiple analysis of variance, we
      demonstrated that nor material composition nor surface roughness amplitude did
      influence cell proliferation, whereas a very significant influence of the process
      used to produce the surface was observed meaning that the main influent factor on
      cell proliferation was the surface morphology. The long-term adhesion and
      proliferation capacity of cells were positively correlated on 23 types of
      substrates on 30, this positive correlation being statistically asserted on 13
      types of substrates on 23. This study is the first demonstration of the existence
      of a statistical correlation between long-term adhesion and proliferation
      capacity of human bone cells on substrates with various chemical composition,
      surface chemistry, and surface topography.

PMID- 15558593
TI  - Analysis of a successful HCV-specific CD8+ T cell response in patients with
      recurrent HCV-infection after orthotopic liver transplantation.
AB  - Virus-specific CD8+ T cells play a major role in antiviral immune defenses; their
      significance in the transplant setting, however, is unclear. In the present
      study, we asked whether hepatitis C virus (HCV)-specific CD8+ T cells were
      detectable in the presence of an immunosuppressive treatment and whether the HCV
      specific CD8+ T cell response correlates with treatment outcome in patients who
      receive interferon (IFN)-alpha / ribavirin therapy after orthotopic liver
      transplantation (OLTx). Liver- and blood-derived T cell lines of 21 patients
      after OLTx were studied before, at the end of, and after antiviral treatment.
      Virus-specific IFN-gamma production in response to a panel of previously
      identified HCV-specific epitopes restricted by the human leukocyte antigen (HLA)
      class I molecules A2, A3, B7, B35, and B44 of structural and nonstructural HCV
      protein was determined by enzyme-linked immunospot (ELISPOT) assay. Before
      treatment, only low numbers of HCV-specific CD8+ T cells were detectable. In 6
      patients with a sustained virological response, a significant, multispecific, and
      sustained CD8+ T cell response was detectable, which was mainly found in the
      peripheral blood. Nonresponders and transient responders showed undetectable,
      weak, or transient HCV-specific CD8+ T cell responses. (Sustained responders vs.
      transient and nonresponders: Wilcoxon rank-signed test; P < .01). In conclusion,
      our data indicate that despite immunosuppression, HCV-specific CD8+ T cells are
      detectable in patients with recurrent HCV infection after OLTx and that a
      significant, multispecific, and long-lasting HCV-specific CD8+ T cell response
      contributes to viral elimination.

PMID- 15558594
TI  - Enhancing the electron transfer capacity and subsequent color removal in
      bioreactors by applying thermophilic anaerobic treatment and redox mediators.
AB  - The effect of temperature, hydraulic retention time (HRT) and the redox mediator
      anthraquinone-2,6-disulfonate (AQDS), on electron transfer and subsequent color
      removal from textile wastewater was assessed in mesophilic and thermophilic
      anaerobic bioreactors. The results clearly show that compared with mesophilic
      anaerobic treatment, thermophilic treatment at 55 degrees C is an effective
      approach for increasing the electron transfer capacity in bioreactors, and thus
      improving the decolorization rates. Furthermore, similar color removals were
      found at 55 degrees C between the AQDS-free and AQDS-supplemented reactors,
      whereas a significant difference (up to 3.6-fold) on decolorization rates
      occurred at 30 degrees C. For instance, at an HRT of 2.5 h and in the absence of
      AQDS, the color removal was 5.3-fold higher at 55 degrees C compared with 30
      degrees C. The impact of a mix of mediators with different redox potentials on
      the decolorization rate was investigated with both industrial textile wastewater
      and the azo dye Reactive Red 2 (RR2). Color removal of RR2 in the presence of
      anthraquinone-2-sulfonate (AQS) (standard redox potential E(0)' of -225 mV) was
      3.8-fold and 2.3-fold higher at 30 degrees C and 55 degrees C, respectively, than
      the values found in the absence of AQS. Furthermore, when the mediators 1,4
      benzoquinone (BQ) (E(0)' of +280 mV), and AQS were incubated together, there was
      no improvement on the decolorization rates compared with the bottles solely
      supplemented with AQS. Results imply that the use of mixed redox mediators with
      positive and negative E(0)' under anaerobic conditions is not an efficient
      approach to improve color removal in textile wastewaters.

PMID- 15558595
TI  - Efficient recognition of protein fold at low sequence identity by conservative
      application of Psi-BLAST: validation.
AB  - A substantial fraction of protein sequences derived from genomic analyses is
      currently classified as representing 'hypothetical proteins of unknown function'.
      In part, this reflects the limitations of methods for comparison of sequences
      with very low identity. We evaluated the effectiveness of a Psi-BLAST search
      strategy to identify proteins of similar fold at low sequence identity. Psi-BLAST
      searches for structurally characterized low-sequence-identity matches were
      carried out on a set of over 300 proteins of known structure. Searches were
      conducted in NCBI's non-redundant database and were limited to three rounds. Some
      614 potential homologs with 25% or lower sequence identity to 166 members of the
      search set were obtained. Disregarding the expect value, level of sequence
      identity and span of alignment, correspondence of fold between the target and
      potential homolog was found in more than 95% of the Psi-BLAST matches.
      Restrictions on expect value or span of alignment improved the false positive
      rate at the expense of eliminating many true homologs. Approximately three
      quarters of the putative homologs obtained by three rounds of Psi-BLAST revealed
      no significant sequence similarity to the target protein upon direct sequence
      comparison by BLAST, and therefore could not be found by a conventional search.
      Although three rounds of Psi-BLAST identified many more homologs than a standard
      BLAST search, most homologs were undetected. It appears that more than 80% of all
      homologs to a target protein may be characterized by a lack of significant
      sequence similarity. We suggest that conservative use of Psi-BLAST has the
      potential to propose experimentally testable functions for the majority of
      proteins currently annotated as 'hypothetical proteins of unknown function'.

PMID- 15558596
TI  - "Doc, should I accept this offer or not?".

PMID- 15558597
TI  - Cell weight kinetics simulation in chemostat and batch culture of the rhodophyte
      Porphyridium cruentum.
AB  - Experimental observations of cell size variations in the proliferating rhodophyte
      Porphyridium cruentum cultured under fully controlled conditions showed
      significant decreases from inoculation to a steady state in the chemostat with
      0.23 d(-1) dilution rate and to a minimum in batch, dropping in size by ratios of
      over 10. To numerically simulate these variations, we assumed that the cell is
      made up of two categories of components that behave differently during the
      interphase and mitosis. These have been called essential (EC) and accessory (AC)
      components. It is assumed that the cell divides once the EC have doubled in size,
      regardless of the AC's state. The experimental cell weight time courses were
      correctly simulated by a model of synchronous cell kinetics based on these
      assumptions. The EC's specific growth rate was 1.5 times that of the whole cell,
      when no limitation occurred. The increase in cell weight observed during batch
      cultures after nutrient exhaustion was suitably simulated by assuming that EC
      growth stops when a limiting nutrient is exhausted. Several parameters
      characterizing the cell kinetics were defined, particularly the minimum minimorum
      EC or cell weight (26 and 15 pg for chemostat and batch, respectively), which was
      influenced by the cultivation method, and the maximum whole cell weight (224 to
      244 pg), which depended on the inoculum's age. The influence of culture
      conditions on the amount of essential and accessory components contained in a
      cell was examined. A new approach was developed with respect to these
      compartments to determine the most suitable strategy and conduct a predictive
      approach for valuable molecule production.

PMID- 15558598
TI  - Substrate range of acetohydroxy acid synthase I from Escherichia coli in the
      stereoselective synthesis of alpha-hydroxy ketones.
AB  - Acetohydroxy acid synthase I appears to be the most effective of the AHAS
      isozymes found in Escherichia coli in the chiral synthesis of phenylacetyl
      carbinol from pyruvate and benzaldehyde. We report here the exploration of a
      range of aldehydes as substrates for AHAS I and demonstrate that the enzyme can
      accept a wide variety of substituted benzaldehydes, as well as heterocyclic and
      heteroatomic aromatic aldehydes, to produce chiral carbinols. The active site of
      AHAS I does not appear to impose serious steric constraints on the acceptor
      substrate. The influence of electronic effects on the reaction has been probed
      using substituted benzaldehydes as substrates. The electrophilicity of the
      aldehyde acceptor substrates is most important to their reactivity, but the
      lipophilicity of substituents also affects their reactivity. AHAS I is an
      effective biosynthetic platform for production of a variety of alpha-hydroxy
      ketones, compounds with considerable potential as pharmacological precursors.

PMID- 15558599
TI  - Expanded criteria donor grafts for deceased donor liver transplantation under the
      MELD system: a decision analysis.
AB  - Expanded criteria donor (ECD) liver grafts have a higher likelihood of primary
      graft failure (PGF) compared with standard criteria donor (SCD) grafts. Given a
      choice between an available ECD graft versus waiting for an SCD graft that may
      not always become available, what should liver transplant candidates do? The
      study's aim was to estimate 1-year survival comparing immediate ECD liver
      grafting with waiting for an SCD organ. Using UNOS data, published literature
      estimates, and expert opinion, we constructed a Markov decision analytic model to
      estimate survival while waiting for an SCD transplant and survival with immediate
      ECD transplant. Sensitivity analyses were performed by varying model parameters
      individually and simultaneously with a second-order Monte Carlo simulation. For
      all patients with MELD scores >20, survival was higher with immediate ECD
      transplant despite the additional increased risk for PGF. Survival was better
      with an immediate ECD transplant unless the probability of PGF exceeded 23%, 72%,
      and 88% for recipients with MELD scores of 11-20, 21-25, and 26-30 respectively.
      For patients with MELD scores >30, the survival benefit with the immediate ECD
      strategy persisted at even higher rates of PGF. In conclusion, our results
      suggest that, despite the higher risk for PGF, transplantation with an available
      ECD graft should be preferred over waiting for an SCD organ for patients with
      advanced MELD scores. At less advanced MELD scores, the survival benefit depends
      on the risk of PGF associated with the ECD organ.

PMID- 15558600
TI  - Exercise-induced stridor due to abnormal movement of the arytenoid area:
      videoendoscopic diagnosis and characterization of the "at risk" group.
AB  - We evaluated 4 patients who developed severe, symptomatic stridor during maximal
      cardiopulmonary exercise testing, all referred due to exercise-related dyspnea.
      All underwent resting, unsedated transnasal fiberoptic laryngoscopy and had
      normal findings. Four patients performed repeat maximal exercise testing with
      fiberoptic laryngoscopy, and they form the basis of this report. They had normal
      vocal cord motion during exercise, but developed abnormal anterior motion of the
      arytenoid and aryepiglottic folds only at peak exercise, leading to partial
      airway obstruction and severe stridor. This report details the workup and
      characterizes patients at risk for this unusual phenomenon.

PMID- 15558602
TI  - Characterization of the denaturation of human alpha-lactalbumin in urea by
      molecular dynamics simulations.
AB  - Molecular dynamics (MD) simulations were used to characterize the non-cooperative
      denaturation of the molten globule A-state of human alpha-lactalbumin by urea. A
      solvent of explicit urea and water molecules was used, corresponding to a urea
      concentration of approximately 6M. Three simulations were performed at
      temperatures of 293K, 360K and 400K, with lengths of 2 ns, 8 ns and 8 ns
      respectively. The results of the simulations were compared with experimental data
      from NMR studies of human alpha-lactalbumin and related peptides. During the
      simulations, hydrogen bonds were formed from the protein to both urea and water
      molecules as intra-protein hydrogen bonds were lost. Urea was shown to compete
      efficiently with water as both a hydrogen bond donor and acceptor. Radial
      distribution functions of water and urea around hydrophobic side chain atoms
      showed a significant increase in urea molecules in the solvation shell as the
      side chains became exposed during denaturation. A considerable portion of the
      native-like secondary structure persisted throughout the simulations. However, in
      the simulations at 360K and 400K, there were substantial changes in the packing
      of aromatic and other hydrophobic side chains in the protein, and many native
      contacts were lost. The results suggest that during the non-cooperative
      denaturation of the molten globule, secondary structure elements are stabilized
      by non-specific, non-native interactions.

PMID- 15558603
TI  - Topological determinants of protein unfolding rates.
AB  - For proteins that fold by two-state kinetics, the folding and unfolding processes
      are believed to be closely related to their native structures. In particular,
      folding and unfolding rates are influenced by the native structures of proteins.
      Thus, we focus on finding important topological quantities from a protein
      structure that determine its unfolding rate. After constructing graphs from
      protein native structures, we investigate the relationships between unfolding
      rates and various topological quantities of the graphs. First, we find that the
      correlation between the unfolding rate and the contact order is not as prominent
      as in the case of the folding rate and the contact order. Next, we investigate
      the correlation between the unfolding rate and the clustering coefficient of the
      graph of a protein native structure, and observe no correlation between them.
      Finally, we find that a newly introduced quantity, the impact of edge removal per
      residue, has a good overall correlation with protein unfolding rates. The impact
      of edge removal is defined as the ratio of the change of the average path length
      to the edge removal probability. From these facts, we conclude that the protein
      unfolding process is closely related to the protein native structure.

PMID- 15558604
TI  - Randomized trial comparing two natural surfactants (Survanta vs. bLES) for
      treatment of neonatal respiratory distress syndrome.
AB  - Exogenous surfactants have been used as an effective treatment of neonatal
      respiratory distress syndrome (RDS). Different preparations of surfactant carry
      different biophysical and clinical properties. To study the response pattern and
      treatment outcome of two natural surfactants (bLES and Survanta) for the
      treatment of RDS, we conducted a randomized clinical trial at the neonatal unit
      of a university teaching hospital. Premature babies with birth weight between 500
      1,800 g who developed RDS requiring mechanical ventilation with an oxygen
      requirement of more than 30% within 6 hr of life were randomized into two
      treatment groups. Oxygenation indices (OIs) within 12 hr of treatment were
      compared as primary outcomes, while neonatal complications were analyzed as
      secondary outcomes of the study. Sixty babies were recruited, with 29 in the bLES
      and 31 in the Survanta treatment group. Both groups had significant and sustained
      improvements in OI after surfactant replacement therapy (SRT), while the bLES
      group was associated with a significantly lower OI throughout the initial 12 hr
      after treatment compared with the Survanta group. There was no difference in
      secondary outcomes including mortality, ventilator days, and occurrence of
      chronic lung disease. We conclude that infants with RDS respond favorably to both
      types of surfactant replacement, and that bLES achieved a faster clinical
      response in terms of improvement in OI than Survanta.

PMID- 15558605
TI  - Leptin, adiposity, and testosterone in captive male macaques.
AB  - Leptin is considered to act as a signal relating somatic energetic status to the
      reproductive system. However, the nature of that signal and its relationship with
      male reproductive function across nonhuman primate species are unclear. We
      suggest that species-specific differences in leptin physiology may be related to
      the degree of environmental variation and variation in the importance of energy
      stores for male reproduction. In order to test the role of seasonality in species
      differences among nonhuman primates, we compared leptin, testosterone, and body
      composition in male rhesus (n = 69) and pig-tailed (n = 43) macaques. Despite
      having larger abdominal fat deposits, the rhesus macaques did not exhibit
      significantly higher leptin levels (rhesus, 2.21 +/- 0.43 ng/ml; pig-tailed, 2.12
      +/- 0.39 ng/ml). Both species showed increases in leptin across adolescent,
      subadult, and adult age-groups (P = 0.036 for rhesus; P = 0.0003 for pig-tailed
      by ANCOVA). Testosterone was not significantly associated with leptin in either
      the rhesus (r = 0.039; P = 0.754) or pig-tailed (r = 0.2862; P = 0.066) samples.
      Comparison of leptin levels across the two species using univariate modeling
      procedures showed no significant age-group by abdominal fat interaction. These
      findings suggest little difference in leptin production between these two closely
      related species, despite the difference in breeding seasonality.

PMID- 15558606
TI  - Foramen magnum position variation in Pan troglodytes, Plio-Pleistocene hominids,
      and recent Homo sapiens: implications for recognizing the earliest hominids.
AB  - The anteroposterior position of the foramen magnum distinguishes living Homo
      sapiens from apes, and has been used as evidence for the hominid status of
      numerable fossils in the history of human paleontology. During the past decade,
      foramen magnum position has been cited as evidence of the hominid status of
      Ardipithecus and Sahelanthropus. Specifically, the basion of Ardpithecus is
      reported to be inline with the bicarotid chord, while the basion of
      Sahelanthropus is reported to both touch the biporion chord and intersect the
      bicarotid chord. In order to assess the effectiveness of anteroposterior foramen
      magnum position in distinguishing hominids from nonhominid apes, this study
      examined whether or not the positions of biporion and bicarotid relative to
      basion sufficiently distinguished Pan troglodytes from recent Homo sapiens and
      Plio-Pleistocene hominids. The distances from basion to the biporion chord
      (BSBIP) and from basion to the bicarotid chord (BSBIC) were measured on samples
      of chimpanzee (n = 69) and recent human (n = 42) crania and a sample of Plio
      Pleistocene hominid fossils (n = 8). The data were used to test the hypothesis
      that BSBIP and BSBIC measurements do not sufficiently distinguish P. troglodytes
      from hominids. While basion to biporion (BSBIP) does not effectively distinguish
      P. troglodytes from Plio-Pleistocene hominids and humans when used univariately,
      basion to bicarotid (BSBIC), when used univariately or bivariately with BSBIP,
      can be used to test whether or not an unknown specimen is a hominid. These
      results are used to evaluate the hominid status of Ardipithecus and
      Sahelanthropus.

PMID- 15558607
TI  - Use of laryngeal mask airway in flexible bronchoscopy in infants and children.
AB  - In the past two decades, flexible bronchoscopy (FB) has gained increasing
      popularity among pediatric pulmonologists. The objective of this study was to
      review our experience with pediatric flexible bronchoscopy over the past 15
      years, with special focus on route of bronchoscopy. This is a retrospective
      study. We reviewed our pediatric FB procedures performed at the University of
      Michigan, Mott Children's Hospital, from 1988-2003. The study included 1,947
      procedures in 1,548 patients, with a mean of 1.3 procedures/patient. The
      male:female ratio was 1.66:1, and age was 4.9 +/- 5.6 years (mean +/- SD).
      Patients <2 years of age represented 46.6% of the study population. The laryngeal
      mask airway (LMA) was the most common route for flexible bronchoscopy in children
      2 years of age and above. Complication rates were lower with the use of the LMA
      (1.9%) compared to the nasal route (3.5%). Stridor was the most common indication
      in the age group <2 years (20.8%), while persistent pulmonary infiltrates were
      more common in the older age groups (32.2-37%). Laryngomalacia was the most
      common finding in patients with stridor (31.5%), while inflammatory changes were
      more common with other indications. Procedure-related complications were reported
      in 2.3% of procedures. Bronchoalveolar lavage (BAL) samples were obtained and
      analyzed in 51.2% of FB procedures (n=1,000), of which 19.4% yielded positive
      microbiology cultures. In conclusion, FB is a safe procedure in pediatrics.
      Children less than 7 years of age represent the majority of FB subjects. The LMA
      offered a lower rate of procedure-related complications when compared to the
      nasal route or endotracheal tube. It also reduced procedure time and anesthesia
      time.

PMID- 15558608
TI  - Evaluation of antihypoxemic maneuvers before tracheal aspiration in mechanically
      ventilated newborns.
AB  - Periodical tracheal aspiration in mechanically ventilated patients is necessary
      to remove mucus from the airways. In children and adults, this procedure causes
      transient hypoxemia, which may be prevented by hyperoxia and/or hyperventilation.
      These findings, however, have not been sufficiently assessed in newborn infants.
      Thus we investigated the usefulness of hyperoxia and/or hyperventilation as
      antihypoxemic maneuvers before tracheal aspiration in newborn infants. Our design
      was a prospective, randomized, multiple crossover study. The setting was the NICU
      of a third-level pediatric hospital in Mexico City. Patients included 15 newborn
      infants under mechanical ventilation. Within a 12-hr period, every patient
      received, in random order, three antihypoxemic maneuvers during 1 min just before
      tracheal aspiration: hyperoxia (10% increase of baseline FiO2), hyperventilation
      (50% increase of ventilator cycling rate), or both. Additionally, a control
      (sham) maneuver was also applied. Pulse oximeter saturation (SpO2) was recorded
      before and after each antihypoxemic maneuver, and at 0, 15, 30, 60, and 300 sec
      after tracheal aspiration. Basal values of SpO2 (81.5 +/- 1.5%) increased with
      all three antihypoxemic maneuvers (SpO2 over 90%, P <0.05 to P <0.01).
      Immediately after tracheal aspiration a drop in the SpO2 could be detected in all
      infants. However, patients receiving hyperoxia showed higher SpO2 values (87.1 +/
      1.8%) than those observed with the sham maneuver (76.9 +/- 2.3%, P <0.01). From
      this point on, all newborn infants in all conditions (even those with sham
      maneuver) had spontaneous increments of SpO2 that at 300 sec were again higher
      than their respective basal values (P <0.05 to P <0.0005). At this time, SpO2
      values from following the hyperoxia maneuver were still higher than those
      following the sham maneuver (P <0.05). Our results show that, similar to what
      occurs at other ages, tracheal aspiration in mechanically ventilated newborn
      infants causes transient hypoxemia, which can be partially prevented by previous
      application of antihypoxemic maneuvers, especially hyperoxia.

PMID- 15558609
TI  - Dental perspectives on the population history of Southeast Asia.
AB  - This article uses metric and nonmetric dental data to test the "two-layer" or
      immigration hypothesis whereby Southeast Asia was initially occupied by an
      "Australo-Melanesian" population that later underwent substantial genetic
      admixture with East Asian immigrants associated with the spread of agriculture
      from the Neolithic period onwards. We examined teeth from 4,002 individuals
      comprising 42 prehistoric and historic samples from East Asia, Southeast Asia,
      Australia, and Melanesia. For the odontometric analysis, dental size proportions
      were compared using factor analysis and Q-mode correlation coefficients, and
      overall tooth size was also compared between population samples. Nonmetric
      population affinities were estimated by Smith's distances, using the frequencies
      of 16 tooth traits. The results of both the metric and nonmetric analyses
      demonstrate close affinities between recent Australo-Melanesian samples and
      samples representing early Southeast Asia, such as the Early to Middle Holocene
      series from Vietnam, Malaysia, and Flores. In contrast, the dental
      characteristics of most modern Southeast Asians exhibit a mixture of traits
      associated with East Asians and Australo-Melanesians, suggesting that these
      populations were genetically influenced by immigrants from East Asia. East Asian
      metric and/or nonmetric traits are also found in some prehistoric samples from
      Southeast Asia such as Ban Kao (Thailand), implying that immigration probably
      began in the early Neolithic. Much clearer influence of East Asian immigration
      was found in Early Metal Age Vietnamese and Sulawesi samples. Although the
      results of this study are consistent with the immigration hypothesis, analysis of
      additional Neolithic samples is needed to determine the exact timing of
      population dispersals into Southeast Asia.

PMID- 15558610
TI  - Mitochondrial sequence variation in the Guahibo Amerindian population from
      Venezuela.
AB  - New data were obtained on mitochondrial DNA (mtDNA) from Guahibo from Venezuela,
      a group so far not studied using molecular data. A population sample (n = 59) was
      analyzed for mtDNA variation in two control-region hypervariable segments (HV1
      and HV2) by sequencing. The presence or absence of a 9-bp polymorphism in the
      COII/tRNA(Lys) region was studied by direct amplification and electrophoretic
      identification. Thirty-eight variable sites were detected in regions HV1 and HV2,
      defining 26 mtDNA lineages; 23.7% of these were present in a single individual.
      The 9-bp deletion was found in 3.39% of individuals. Nucleotide and haplotype
      diversities were relatively high compared with other New World populations. The
      identified sequence haplotypes were classified into four major haplogroups (A-D)
      according to previous studies, with high frequencies for A (47.46%) and C
      (49.15%), low frequency for B (3.39%), and an absence of D.

PMID- 15558611
TI  - Sonography of bone and bone-related diseases of the extremities.

PMID- 15558613
TI  - Biaxial flexure testing of calcium phosphate bioceramics for use in tissue
      engineering.
AB  - This study analyzes data from 206 CaP specimens (68 HA, 70 BCP, and 68 beta-TCP)
      fractured via biaxial flexure testing. Specimens were divided into four groups:
      (a) Group I, dry; (b) Group II, wet (day 0, immersion time approximately 5-10 s);
      (c) Group III, after immersion in media for 21 days (day 21); and (d) Group IV,
      after culturing osteoblasts (OBs) on the surface for 21 days (day 21 with cells).
      X-ray diffraction verified the presence of minor second phases in HA and beta-TCP
      while BCP was a biphasic mixture of HA and beta-TCP with minor phases present.
      The statistical significance (p < 0.05) of differences in the measured biaxial
      flexure fracture strength, S, between groups was assessed via one-way ANOVA with
      Tukey's test. Also, a two-parameter Weibull analysis assessed the mechanical
      reliability of each group. Osteoblasts increase the biaxial flexure fracture
      strength in a statistically significant way compared to both the HA discs in
      Groups II and III. Scanning electron microscope examination revealed grain
      boundary grooving on the sintered surfaces and with thermal expansion anisotropy,
      likely leads to the observed rapid strength decline upon exposure to media found
      in Groups II, III and IV.

PMID- 15558614
TI  - Bite force production capability and efficiency in Neandertals and modern humans.
AB  - Although there is consensus that Neandertal craniofacial morphology is unique in
      the genus Homo, debate continues regarding the precise anatomical basis for this
      uniqueness and the evolutionary mechanism that produced it. In recent years,
      biomechanical explanations have received the most attention. Some proponents of
      the "anterior dental loading hypothesis" (ADLH) maintain that Neandertal facial
      anatomy was an adaptive response to high-magnitude forces resulting from both
      masticatory and paramasticatory activity. However, while many have argued that
      Neandertal facial structure was well-adapted to dissipate heavy occlusal loads,
      few have considered, much less demonstrated, the ability of the Neandertal
      masticatory system to generate these presumably heavy loads. In fact, the
      Neandertal masticatory configuration has often been simultaneously interpreted as
      being disadvantageous for producing large bite forces. With rare exception,
      analyses that attempted to resolve this conflict were qualitative rather than
      quantitative. Using a three-dimensional digitizer, we recorded a sequence of
      points on the cranium and associated mandible of the Amud 1, La Chapelle-aux
      Saints, and La Ferrassie 1 Neandertals, and a sample of early and recent modern
      humans (n = 29), including a subsample with heavy dental wear and documented
      paramasticatory behavior. From these points, we calculated measures of force
      production capability (i.e., magnitudes of muscle force, bite force, and condylar
      reaction force), measures of force production efficiency (i.e., ratios of force
      magnitudes and muscle mechanical advantages), and a measure of overall size
      (i.e., the geometric mean of all linear craniofacial measurements taken). In
      contrast to the expectations set forth by the ADLH, the primary dichotomy in
      force-production capability was not between Neandertal and modern specimens, but
      rather between large (robust) and small (gracile) specimens overall. Our results
      further suggest that the masticatory system in the genus Homo scales such that a
      certain level of force-production efficiency is maintained across a considerable
      range of size and robusticity. Natural selection was probably not acting on
      Neandertal facial architecture in terms of peak bite force dissipation, but
      rather on large tooth size to better resist wear and abrasion from submaximal
      (but more frequent) biting and grinding forces. We conclude that masticatory
      biomechanical adaptation does not underlie variation in the facial skeleton of
      later Pleistocene Homo in general, and that continued exploration of alternative
      explanations for Neandertal facial architecture (e.g., climatic, respiratory,
      developmental, and/or stochastic mechanisms) seems warranted.

PMID- 15558615
TI  - Sonography of the knee: intra-articular pathology.
AB  - MRI is the gold-standard imaging technique for evaluation of the intra-articular
      structures of the knee, and the use of sonography remains controversial.
      Sonography nevertheless is a useful alternative in several conditions:
      Inflammatory joint diseases, where it is appropriate for early diagnosis and
      follow-up of joint effusion and synovitis; peri-articular masses, where it is the
      best modality for guidance of needle puncture or biopsy; suspected meniscus or
      ligament lesion, where it may provide a positive diagnosis but is not sufficient
      to exclude intra-articular lesions; and loose bodies, where it is an outstanding
      modality for diagnosing lesions not evident on radiographs.

PMID- 15558616
TI  - Sonography of the thoracic and abdominal walls.
AB  - Pathologic processes that may involve the thoracic or abdominal wall occasionally
      raise diagnostic challenges because of the low specificity of physical findings.
      Congenital and developmental anomalies may mimic soft-tissue or bone tumors;
      tumors may mimic inflammatory and infectious diseases, and vice versa.
      Furthermore, these disorders may produce remote manifestations that are
      frequently misdiagnosed as visceral pain. Many of these parietal processes have
      typical sonographic appearances that allow definitive diagnosis. This article
      reviews characteristic sonographic appearances of thoracic and abdominal wall
      disorders. Familiarity with these sonographic features facilitates accurate
      diagnosis and optimal patient treatment.

PMID- 15558617
TI  - Toward a useful mass movement.
AB  - Psychology has failed to reach its full potential as either a science or a
      profession. The inability of psychologists to generate a shared, general
      understanding of their subject matter and fundamental differences between
      scientific and nonscientific views of human behavior in society at large interact
      to render psychology's contributions to the world's most pressing problems much
      less potent than might otherwise be the case. The Tree of Knowledge (ToK) System
      affords new opportunities both to define the discipline of psychology and to
      examine the epistemological interrelations between the institution of science and
      other societal institutions, such as law, governance, health care, the arts, and
      religion. In this article I articulate how the foundation can be laid for the
      development of a useful mass movement that could transform the discipline of
      psychology in a manner that unleashes its constructive potential, while at the
      same time it attempts to address many of the concerns about the proposal raised
      by the contributors to these two special issues.

PMID- 15558618
TI  - GEE estimation of a misspecified time-varying covariate: an example with the
      effect of alcoholism treatment on medical utilization.
AB  - The generalized estimation equation (GEE) method is widely used in longitudinal
      data analysis, particularly when the outcome variable is non-Gaussian
      distributed. Under mild regulatory conditions, the parameter estimates are
      consistent and their asymptotic variances are efficient. In an observational
      study focusing on alcoholism patients, we applied the GEE method to longitudinal
      count data from medical utilization records from a large national managed care
      organization. The health services research question was whether there was a
      change in medical utilization for patients after engaging in alcoholism treatment
      as compared to before treatment. Thus, the main effect of interest was a time
      varying covariate indicating whether the patient had undergone treatment yet or
      not. GEE under five different working correlations was employed and mixed results
      regarding the significance of the treatment effect were found. Because of the
      large sample size, i.e. 8485 patients with an average of 46 repeated measurements
      per patient, differences across the estimates produced by the different working
      correlation structures was suspicious. It is shown that these differences are
      maybe caused by the fact that the time-varying covariate in the marginal mean
      model is misspecified. A simulation study is performed to demonstrate that
      misspecification of the time-varying covariate in the marginal mean structure can
      cause differences in GEE results across various choices of working correlation
      structure.

PMID- 15558619
TI  - Sonography of the hand: tendon pathology, vascular disease, and soft tissue
      neoplasms.

PMID- 15558620
TI  - The motivation to control and the origin of mind: exploring the life-mind joint
      point in the Tree of Knowledge System.
AB  - The evolved function of brain, cognitive, affective, conscious-psychological, and
      behavioral systems is to enable animals to attempt to gain control of the social
      (e.g., mates), biological (e.g., prey), and physical (e.g., nesting spots)
      resources that have tended to covary with survival and reproductive outcomes
      during the species' evolutionary history. These resources generate information
      patterns that range from invariant to variant. Invariant information is
      consistent across generations and within lifetimes (e.g., the prototypical shape
      of a human face) and is associated with modular brain and cognitive systems that
      coalesce around the domains of folk psychology, folk biology, and folk physics.
      The processing of information in these domains is implicit and results in
      automatic bottom-up behavioral responses. Variant information varies across
      generations and within lifetimes (e.g., as in social dynamics) and is associated
      with plastic brain and cognitive systems and explicit, consciously driven top
      down behavioral responses. The fundamentals of this motivation-to-control model
      are outlined and links are made to Henriques' (2004) Tree of Knowledge System and
      Behavioral Investment Theory.

PMID- 15558621
TI  - Testing the limits of Henriques' proposal: Wittgensteinian lessons and
      hermeneutic dialogue.
AB  - The limits of Henriques' "overarching conceptions" approach to defining
      psychology is first tested by comparing and contrasting his conceptions to two
      burgeoning movements within psychology: qualitative research and spiritual
      therapy strategies. These movements were selected because they represent many
      other fragments of a fragmented psychology that could fall outside Henriques'
      disciplinary matrix. This comparison reveals how the broader discipline of
      psychology resists propositional definitions, such as Henriques' proposal. As the
      later work of Wittgenstein (1958) reveals, one cannot unite the various language
      games of a discipline's discourse communities through common overarching
      features. Next, another approach to unification and definition is outlined-
      hermeneutic dialogue. Unlike an overarching framework, hermeneutic dialogue does
      not require "joint points." In fact, it assumes that the richness and vitality of
      a discipline can be drained away by such "unifying" principles. Instead,
      hermeneutic dialogue is a way of relating and unifying while preserving the
      integrity and identity of even incommensurable factions within a discipline.

PMID- 15558622
TI  - Sonography of entrapment neuropathies in the upper limb (wrist excluded).
AB  - The progressive refinement of broadband transducers with frequencies higher than
      10 MHz and improved near-field resolution has enhanced the potential of
      sonography to evaluate a variety of nerve entrapment syndromes occurring in the
      upper limb, such as suprascapular neuropathy in the area of the spinoglenoid
      supraspinous notch, the quadrilateral space syndrome (axillary neuropathy),
      radial neuropathy in the area of the spiral groove, the supinator syndrome
      (posterior interosseous neuropathy), the cubital tunnel syndrome (ulnar
      neuropathy), and the Kiloh-Nevin syndrome (anterior interosseous neuropathy). In
      these settings, high-resolution sonography can depict changes in the nerve's
      shape and echotexture and can depict many extrinsic causes of nerve entrapment.

PMID- 15558623
TI  - High-resolution sonography of compressive neuropathies of the wrist.

PMID- 15558624
TI  - Justifying the Justification Hypothesis: scientific-humanism, Equilintegration
      (EI) Theory, and the Beliefs, Events, and Values Inventory (BEVI).
AB  - The Justification Hypothesis (JH; Henriques, 2003) is a basic, general, and macro
      level construct that is highly compelling. However, it needs greater
      specification (i.e., justification) regarding what it is, how it might be
      operationalized and measured, and what it does and does not predict in the real
      world. In the present analysis, the act of "justification" is conceptualized as
      the ongoing attempt to convince self and/or others that one's beliefs and values,
      which is to say one's "version of reality" or VOR, is correct, defensible, and
      good. In addressing these issues, this paper is divided into two complementary
      parts: (a) consideration of justification dynamics and exemplars from a
      scientific-humanist perspective and (b) an examination of how justification
      systems and processes have been studied vis-a-vis research and theory on beliefs
      and values as well as an extant model--Equilintegration (EI) Theory--and method-
      the Beliefs, Events, and Values Inventory (BEVI).

PMID- 15558625
TI  - From mirror self-recognition to the looking-glass self: exploring the
      Justification Hypothesis.
AB  - In his Tree of Knowledge (ToK) System, Henriques (2003) posits that the human ego
      or "self" has evolved because human beings are the only animals that have had to
      justify their behavior to others. This essay provides evidence for this
      Justification Hypothesis (JH) from everyday life sociology, starting with the
      work of George Herbert Mead and Charles Horton Cooley, and focuses on research
      related to the concept of the "looking-glass self." Special emphasis is given to
      the pragmatics of speech acts, the presentation of self in interaction rituals,
      the accounts given by actors in justification of their actions, and the role of
      social norms and conformity in the large-scale justification systems commonly
      called "culture."

PMID- 15558626
TI  - Sonography of ankle ligaments.

PMID- 15558628
TI  - Toward a consilient science of psychology.
AB  - From its inception, psychology has been characterized by conceptual fragmentation
      and slow scientific progress (Henriques, 2004; Meehl, 1978). In contrast, the
      natural sciences have achieved in recent decades a remarkable degree of
      consilience--the linking of fact, theory, and method across disciplines (and
      subdisciplines) and across nested levels of informational complexity (Wilson,
      1998). Although such consilience serves as a potent catalyst of scientific
      discovery, there exists several barriers to the emergence of a consilient science
      of psychology (e.g., the persistent influence of dualism, longstanding
      internecine discord, resistance to perceived reductionism, etc.). We discuss the
      manner in which the development of metatheoretical frameworks (including
      Henriques' Tree of Knowledge model) may play an important role in addressing such
      barriers. Likewise, we describe the hybrid interdisciplinary domain of cognitive
      neuroscience, which provides an empirically testable metatheory and a promising
      consilient bridge between psychology and the natural sciences.

PMID- 15558629
TI  - Remythologizing culture: Narrativity, justification, and the politics of
      personalization.
AB  - The thesis that the self is a story unfolding in prescriptive space is typically
      embraced by social constructionists as a radical alternative to naturalistic
      accounts of human development. Yet, the Tree of Knowledge (ToK) System proposed
      by Henriques (2003) implies that events at multiple levels of analysis (i.e.,
      matter, life, mind, and culture) can be considered as conditions of possibility
      for the emergence of meaningful personal narratives. Thus, the ToK System
      represents an opportunity to recast the work of naturalists and social
      constructionists in a framework that is at once scientific and humanistic.

PMID- 15558630
TI  - Anterior shoulder instability: sonographic evaluation.

PMID- 15558631
TI  - Sonography in wrist tendon pathology.
AB  - Wrist tendons may be affected by a variety of pathologic conditions, including
      those caused by trauma and overuse, inflammatory and metabolic disorders, or
      infection. Sonography is a very sensitive means of detecting tendinous pathology
      because of its spatial resolution and its comparative and dynamic capabilities.
      Its wide availability makes it the preferred first-line imaging modality in the
      case of wrist pain. This article reviews the pathologic conditions that may
      involve the wrist and their sonographic appearances.

PMID- 15558634
TI  - Association between a vasopressin receptor AVPR1A promoter region microsatellite
      and eating behavior measured by a self-report questionnaire (Eating Attitudes
      Test) in a family-based study of a nonclinical population.
AB  - OBJECTIVES: Considerable evidence including twin and family studies suggests that
      biologic determinants interact with cultural cues in the etiology of anorexia and
      bulimia nervosa. A gene that makes "biologic sense" in contributing
      susceptibility to these disorders, and to our knowledge not previously
      investigated for this phenotype, is the vasopressin receptor (AVPR1A), which we
      have tested for association with eating pathology. METHODS: We genotyped 280
      families with same-sex siblings for two microsatellites in the promoter region of
      the AVPR1A gene. Siblings completed the 26-item Eating Attitudes Test (EAT) and
      the Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales of the Eating
      Disorders Inventory (EDI). The Quantitative Transmission Disequilibrium Test
      program (QTDT), which employs flexible and powerful variance-components
      procedures, was used to test for an association between EAT scores and the two
      AVPR1A promoter region microsatellites, RS1 and RS3. RESULTS: A significant
      association (p = .036) was detected between the RS3 microsatellite and EAT
      scores. The strongest association was between RS3 and the Dieting subscale of the
      EAT (p = .011). A significant association was also observed between the EDI-DT
      and the RS3 microsatellit (p = .0450). CONCLUSIONS: We demonstrate for the first
      time an association between a microsatellite polymorphism in the AVPR1A promoter
      region and scores on the EAT as well as with the EDI-DT. The strongest
      association was observed between the RS3 microsatellite and the Dieting subscale
      of the EAT. The relevant phenotype appears to tap severe dietary restriction for
      weight loss purposes.

PMID- 15558636
TI  - A claim on the development of the frontier orbital explanation of electrocyclic
      reactions.

PMID- 15558635
TI  - Effects of negative mood induction and impulsivity on self-perceived emotional
      eating.
AB  - OBJECTIVE: The current study investigates the influence of negative mood
      induction and impulsivity on self-perceptions with respect to emotional eating.
      Negative affect as well as high impulsivity was expected to increase levels of
      self-perceived emotional eating. METHOD: College students who were high versus
      low in impulsivity were assigned randomly to either a negative (failure on a
      quiz) or a neutral mood induction. Their levels of self-perceived emotional
      eating were measured after and before mood induction. RESULTS: Negative affect
      appeared to enhance the level of self-perceived emotional eating significantly (p
      < .01). There was no statistically significant effect of impulsivity. The
      interaction effect of affect and impulsivity approached significance (p = .08),
      indicating that highly impulsive subjects compared with subjects low in
      impulsivity were more strongly influenced by negative affect in self-perceived
      emotional eating. DISCUSSION: Negative affect substantially influences self
      perceptions in terms of emotional eating, which is relevant for both prevention
      and treatment.

PMID- 15558637
TI  - The 2 x 3 toolbox of organometallic methods for regiochemically exhaustive
      functionalization.
AB  - This review describes a concept aimed at rational and maximal structure
      proliferation. To this end, simple aromatic or heterocyclic starting materials,
      often bulk chemicals, are converted into all regionisomerically possible polar
      organometallic intermediates (mostly lithiated species), which then may be
      combined with any of the countless electrophiles to provide attractive new
      building blocks, particularly functionalized derivatives. The practical
      implementation relies on a set ("toolbox") of sophisticated recipes developed by
      mechanistically guided modification of the two most prominent exchange methods
      used for the generation of polar organometallic compounds: hydrogen-metal and
      halogen-metal interconversion. These mutant methods ("old methods in a new
      outfit") amplify the existing options for organic synthesis by ensuring maximum
      regioflexibility. At the same time they offer new insight into factors that
      govern organometallic reactivity and provide hints on how to alter or finetune
      this reactivity judiciously.

PMID- 15558638
TI  - The Woodward-Hoffmann rules ...

PMID- 15558640
TI  - Supramolecular catalysis of a unimolecular transformation: aza-Cope rearrangement
      within a self-assembled host.

PMID- 15558639
TI  - Activity-based high-throughput screening of enzymes by using a DNA microarray.

PMID- 15558641
TI  - Absolute optical cross section of individual fluorescent molecules.

PMID- 15558642
TI  - Spectroscopic elucidation of a peroxo Ni2(mu-O2) intermediate derived from a
      nickel(I) complex and dioxygen.

PMID- 15558643
TI  - Evaluation of the local irritation potential of hypertonic saline-dextran (HSD)
      in mice and rabbits.
AB  - Recent questions have renewed concerns regarding possible irritation associated
      with intravenous (i.v.) injection of 7.5% hypertonic saline (HS) or hypertonic
      saline-dextran (HSD: 7.5% NaCl and 6% Dextran-70). This study investigated local
      injection site irritation associated with i.v., paravenous (p.v.), intramuscular
      (i.m.) and subcutaneous (s.c.) injection of HSD or its individual components.
      Mice (n=10 per group per time point) and rabbits (n=10 per group per time point)
      were infused i.v. with the maximum tolerated dose (28 or 20 ml kg(-1),
      respectively) of HSD, HS, Dextran-70 (D-70) or lactated Ringer's solution (LR).
      Animals were observed at 1,2 and 4 h after injection and then twice daily until
      euthanized on day 3 or 14. In irritation studies, 24 rabbits were randomized to
      receive the four fluids and they were evaluated histologically at 4, 24, 48 or 72
      h after i.v., p.v., i.m. or s.c. infusion. The sites were observed immediately
      after injection, at 4 h and then twice daily until euthanasia. In surviving mice,
      bruising of the tail was observed in 6/18 and 5/19 animals in the HSD and HS
      groups, respectively, compared with 0/20 animals in the D-70 or LR groups.
      Sloughing of the tail was eventually observed in two HSD-infused and three HS
      infused mice, compared with none in the other groups. More bruises, hematomas and
      blebs were observed after i.v. or s.c. injection of HS and D-70 than LR or HSD in
      the rabbit irritation studies, but the differences among groups were not
      statistically significant. In the acute toxicity study in rabbits, bruising at
      the site of injection was observed in 7/20 and 5/14 surviving animals from the
      HSD and HS groups, respectively, but none was observed in the LR or D-70 groups.
      These data suggest that, if infused over 5-10 min into a peripheral or central
      vein, a therapeutic dose of HSD (4 ml kg(-1)) should not induce any greater
      inflammation on the vein than LR. However, if significant extravasation of
      hypertonic fluid occurs, the possibility of localized, focal necrosis might be
      expected to occur.

PMID- 15558644
TI  - A comparison of the binge eating scale, questionnaire for eating and weight
      patterns-revised, and eating disorder examination questionnaire with instructions
      with the eating disorder examination in the assessment of binge eating disorder
      and its symptoms.
AB  - OBJECTIVE: The current study assesses concordance between self-administered
      measures and a diagnostic standard for assessment of binge frequency and
      diagnosis of binge eating disorder (BED) in a sample of binge eaters. METHOD: The
      Questionnaire for Eating and Weight Patterns-Revised (QEWP-R), Binge Eating Scale
      (BES), two items from the Eating Disorder Examination Questionnaire with
      Instructions (EDE-Q-I), and the Eating Disorder Examination (EDE) were
      administered. Participants were 157 adults volunteering for a clinical study, of
      whom 129 (79%) were diagnosed with BED using the EDE as the diagnostic standard.
      RESULTS: In the identification of BED, the QEWP-R yielded a sensitivity value of
      .74 and a specificity value of .35. The BES yielded a sensitivity value of .85
      and a specificity value of .20. Frequency of binge eating days and episodes on
      the EDE-Q-I correlated highly with the EDE (.65 and .48, respectively; p < .001).
      DISCUSSION: The accuracy of diagnosis and symptomatology among self-administered
      questionnaires is variable. The BES and the QEWP-R performed satisfactorily as
      initial screens for the diagnosis of BED, but were less accurate in identifying
      non-BED individuals and the frequency of binge eating. The EDE-Q-I most
      accurately assessed the frequency of binge eating.

PMID- 15558645
TI  - Risk factors for body dissatisfaction in adolescent boys and girls: a prospective
      study.
AB  - OBJECTIVE: Despite evidence that body dissatisfaction predicts the onset of
      eating pathology and depression, few prospective studies have investigated
      predictors of body dissatisfaction. METHOD: We examined risk factors for body
      dissatisfaction using prospective data from 531 adolescent boys and girls.
      RESULTS: Elevations in body mass, negative affect, and perceived pressure to be
      thin from peers, but not thin-ideal internalization, social support deficits, or
      perceived pressure to be thin from family, dating partners, or media, predicted
      increases in body dissatisfaction. Gender moderated the effect of body mass on
      body dissatisfaction and revealed a significant quadratic component for boys, but
      not girls. Gender also moderated negative affect. DISCUSSION: Results support the
      assertion that certain sociocultural, biologic, and interpersonal factors
      increase the risk for body dissatisfaction, but differ for boys and girls.
      Results provided little support for other accepted risk factors for body
      dissatisfaction.

PMID- 15558646
TI  - Purging behaviors and comorbidity as predictive factors of quality of life in
      anorexia nervosa.
AB  - OBJECTIVE: This study examined the predictive factors for the physical and mental
      summary components (PCS and MCS) of quality of life (SF-36) in patients with
      anorexia nervosa. METHOD: Forty-seven patients with anorexia nervosa were
      studied. Assessment comprised psychiatric diagnosis by a clinical structured
      interview for Axis I disorders (SCID-I) and personality disorders (SCID-II),
      Clinical Global Impression (CGI), and Quality of Life (SF-36). RESULTS: Anorexia
      nervosa, restrictive type, was diagnosed in 73.9% of the patients and 51% of the
      patients presented with comorbidity on Axis I or Axis II or both. The predictive
      variables for the PCS were poor outcome in previous year, comorbidity on Axes I
      and II, and female gender. The predictive variables for the MCS were the presence
      of comorbidity in one or the other of the Axis I or II disorders and purging
      behaviors. DISCUSSION: The current study suggests the importance of comorbidity
      and purging behaviors in the quality of life of these patients with anorexia
      nervosa.

PMID- 15558647
TI  - Protein chemistry on the surface of living cells.
AB  - The interplay between carbohydrates, lipids, and proteins determines the
      stability and flexibility as well as the adhesive and responsive features of the
      surfaces of all cells. The molecular understanding of the interactions among and
      between the different classes of these biomolecules is rudimentary at best, a
      lack of suitable experimental methods being the major reason. Here we discuss a
      new approach for the specific labeling of fusion proteins of carrier proteins
      with synthetic compounds on cell surfaces and describe how this approach can be
      used to investigate the properties of the labeled molecules.

PMID- 15558648
TI  - Strain- and sex-related differences of carbonyl reductase activities in kidney
      microsomes and cytosol of rats.
AB  - This study was designed to elucidate strain- and sex-related differences of
      carbonyl reductase activity in rat kidney by using the oral antidiabetic drug
      acetohexamide as substrate. The frequency distribution of carbonyl reductase
      activities in kidney microsomes of male Fischer 344 (Fischer), Sprague-Dawley,
      Wistar and Wistar-Imamichi (Wistar-IM) rats exhibited a marked strain-related
      difference. Furthermore, the enzyme activities in kidney microsomes of Fischer,
      Sprague-Dawley and Wistar rats were male-specific, resulting insignificant sex
      related differences in these strains. There was no sex-related difference of
      carbonyl reductase activity in kidney microsomes of the Wistar-IM strain, which
      lacked its activity in both sexes. On the other hand, although carbonyl reductase
      activities were fully detectable in kidney cytosols from all the strains of male
      and female rats, no strain- or sex-related difference was observed among the
      cytosolic enzyme activities. These results provide new information for
      understanding the influence of internal factors on the renal metabolism of ketone
      containing xenobiotics.

PMID- 15558649
TI  - Dissonance thin-ideal and didactic healthy behavior eating disorder prevention
      programs: results from a controlled trial.
AB  - OBJECTIVE: Negative body image, a common problem among college-age women in the
      United States, strongly correlates with low self-esteem, disturbed eating
      behavior, and eating disorders. Psychoeducational programs have inconsistently
      shown improvement in body image, thin-ideal internalization, eating behaviors,
      psychosocial functioning, and self-esteem. METHOD: In the current study, college
      women with body image concerns (N = 84) were randomly assigned to a cognitive
      dissonance-based, thin-ideal internalization, single-session workshop (DTI; n =
      26); a psychoeducational, healthy behavior, single-session workshop (HB; n = 24);
      or a wait-list control (WL; n = 34). RESULTS: Comparing baseline data with 4-week
      follow-up data, results indicated that both DTI and HB participants reported
      improvement in body image, thin-ideal internalization, and eating behaviors.
      DISCUSSION: Results provide evidence that both interventions effectively reduce
      risk factors for eating pathology.

PMID- 15558650
TI  - Binge eating and satiety in bulimia nervosa and binge eating disorder: effects of
      macronutrient intake.
AB  - OBJECTIVE: The current study tested the hypothesis that supplemental dietary
      protein would reduce binge eating frequency and test meal intake in women with
      bulimia nervosa (BN) or binge eating disorder (BED). METHOD: Eighteen women with
      BN or BED ingested high-carbohydrate or high-protein supplements (280 kcal) three
      times daily over two 2-week periods. On the morning after each period,
      participants were given a high-protein or high-carbohydrate supplement (420 kcal)
      3 hr before an ad libitum meal. RESULTS: Binge eating episodes occurred less
      frequently during protein supplementation (1.12 episodes per week) than during
      carbohydrate supplementation (2.94 episodes per week) or baseline (3.01 episodes
      per week). Participants reported less hunger and greater fullness, and consumed
      less food at test meals, after protein than after carbohydrate (673 vs. 856
      kcal). DISCUSSION: Adding protein to the diets of women with BN and BED reduced
      food intake and binge eating over a 2-week period. These findings may have
      implications for the longer-term treatment of these disorders.

PMID- 15558651
TI  - The development of the P-CAN, a measure to operationalize the pros and cons of
      anorexia nervosa.
AB  - OBJECTIVE: Research has suggested that a fundamental aspect of anorexia nervosa
      (AN) is its egosyntonic nature, the fact that it is often valued by individuals
      with the disorder. The current study describes the development of the P-CAN, a
      quantitative measure of both positive (valued) and negative aspects of AN.
      METHOD: Items were derived from a previous qualitative study (Serpell, Treasure,
      Teasdale, & Sullivan. 1999. International Journal of Eating Disorders, 25, 177
      186). Data from 233 women with AN were subjected to a principal components
      analysis. RESULTS: Ten subscales were identified, six describing the pros of AN
      and four describing the cons of the illness. DISCUSSION: The P-CAN shows good
      psychometric properties and should prove a useful tool for the measurement of
      attitudes towards AN, as well as offer insights into the maintenance of the
      disorder.

PMID- 15558652
TI  - Inhalation toxicity in mice exposed to sarin (GB) for 20-720 min.
AB  - Most of the historical data for the toxicity of sarin (GB) was collected for
      exposure times of <10 min in attempts to establish the utility of and defence
      against this agent in offensive military use. However, information concerning the
      toxicity of GB (and other nerve agents) from longer exposures of 1-12 h is
      critical for all personnel who must work in or close to low-level concentrations
      of chemical for extended periods and for all personnel, dressed in Individual
      Protective Equipment, who need to know when, and if, it is safe to take off these
      cumbersome garments.The data presented for the toxicity of GB to mice for whole
      body exposures of 20 min to 12 h are intended to form part of an ongoing, multi
      species effort aimed at establishing toxicity estimates for humans for these
      longer exposure times: LCT50 values of 430, 540, 900, 1210 and 2210 mg.min m(-3)
      or LC50 values of 21.5, 9.0, 5.0, 3.4 and 3.1 mg m(-3) were obtained for mice for
      20-, 60-, 180-, 360- and 720-min exposures to GB, respectively. The data for
      longer exposures do not follow Haber's rule (LCT50=CT). The 20- and 60-min data
      fit the 'toxic load model' involving CnT that was established previously from
      historical data for 0.17-30 min GB exposures to mice. The LCT(50) and LC50 values
      for 3, 6 and 12 h are progressively higher (toxicity lower) than predicted by
      either Haber's rule or the toxic load model.

PMID- 15558653
TI  - Binding of bilirubin and bromosulphthalein to albumin: implications for
      understanding the pathophysiology of liver failure and its management.
AB  - The binding/transporting functions of albumin provide the rationale for using
      albumin dialysis (e.g., molecular adsorbents recirculating system [MARS]) in
      liver failure. This study investigates these properties in vitro, validating the
      findings in vivo. In vitro bromosulphthalein (BSP) and bilirubin-spiked plasma
      were dialyzed against albumin and sampled. In vivo serum biochemistry was
      analyzed in: 7 MARS-treated liver failure patients; 98 MARS-treated patients from
      the MARS Registry; and 8 patients receiving albumin infusion. In vitro BSP
      concentrations did not equilibrate, but the molar ratio of BSP to albumin
      (C(BSP)/C(alb)) did, with no subsequent transmembrane transport, suggesting that
      the C(BSP)/C(alb) gradient (rather than simple diffusion) drives BSP transport.
      Bilirubin was transported similarly. In vivo serum bilirubin reduction during
      MARS sessions (n = 26) correlated with pre-treatment bilirubin (r = 0.42), but
      better (r = 0.85) with pre-treatment molar ratio of bilirubin to albumin
      (C(bilirubin)/C(alb)). The strongest correlation was between C(bilirubin)/C(alb)
      reduction and pre-treatment C(bilirubin)/C(alb) (r = 0.9). A similar pattern was
      observed in the MARS Registry patients. After albumin infusion (n = 8), both
      serum albumin and bilirubin increased, while C(bilirubin)/C(alb) remained
      unchanged. C(bilirubin)/C(alb) appears to be important in albumin dialysis, and
      generally in liver disease patients, reinforcing the importance of the toxin
      binding functions of albumin in liver disease.

PMID- 15558654
TI  - Combined orthotopic heart and liver transplantation: the need for exception
      status listing.
AB  - Through May 2004, 33 combined orthotopic heart-liver transplants (OHT/OLT) have
      been performed nationwide. No published data exist to date regarding outcomes of
      patients awaiting such transplants, although progression of two organ disease
      processes may contribute to premature death for waiting patients. Retrospective
      data were collected on patients listed for combined OHT/OLT from both an
      individual tertiary care transplant center and the national UNOS registry to
      delineate listing criteria and evaluate patient outcomes in both the pre- and
      post-MELD eras. All patients who survived to transplantation or died on the
      waiting list were included in the analysis. Results show that 29.6% of patients
      registered nationally and 42% of patients listed institutionally survived to
      transplantation. Survival to transplantation was associated with less severe
      liver disease, though patients with MELD scores ranging from 19 to 26 had
      significantly higher wait list mortality than expected when compared to single
      organ liver transplants. Following combined orthotopic heart-liver
      transplantation, 80% and 70% of patients survive 1 and 3 years, respectively. In
      conclusion, combined OHT/OLT is a successful therapy, but current organ
      allocation policies may not ensure expeditious transplantation in critically ill
      patients with dual vital organ failure. Providing exception status listing to
      these patients would ensure more expeditious transplantation and potentially
      contribute to improved survival.

PMID- 15558655
TI  - Group cognitive-behavior therapy for bulimia nervosa: statistical versus clinical
      significance of changes in symptoms across treatment.
AB  - BACKGROUND: Cognitive-behavior therapy (CBT) is the most effective treatment to
      date for bulimia nervosa. The current study investigated the effects of group CBT
      treatment (including some interpersonal elements) for bulimic clients. METHOD:
      Twenty-nine patients completed the Stirling Eating Disorder Scales, the Beck
      Depression Inventory, and the Beck Anxiety Inventory at assessment, pretreatment,
      end of treatment, and at 6 months follow-up. Symptom change was explored in two
      ways. Statistically significant change was determined using repeated-measures
      analyses of variance and clinically significant change was determined using
      criteria proposed by Jacobson & Truax (1991, Journal of Consulting and Clinical
      Psychology, 59, 12-19). RESULTS: There was an overall improvement in dimensional
      measures of bulimic and restrictive attitudes and behaviors (maintained at the 6
      month follow-up), which was most closely matched by clinically significant
      changes in bulimic behaviors. Depression (but not anxiety) was also targeted
      effectively. Statistically significant improvements in psychological functioning
      were evident only for assertiveness, but the analysis of clinical significance
      showed improvement for some participants in self-evaluation (self-directed
      hostility). DISCUSSION: Group CBT (including interpersonal elements) is broadly
      effective when treating bulimia nervosa, but it does not work in all cases (and
      may lead to enhancement of restrictive characteristics in some cases). Tests of
      statistical and clinical significance provide different information, which can
      inform practice and aid in the development of treatments for patients who respond
      less well to current best practice.

PMID- 15558656
TI  - Binding of histone H1 to DNA is described by an allosteric model.
AB  - Equilibrium binding data were analyzed to characterize the interaction of the
      linker histone H1 degrees with unmodified T4 phage DNA. Data were cast into the
      Scatchard-type plot described by McGhee and von Hippel and fit to their eponymous
      model for nonspecific binding of ligand to DNA. The data were not fit by the
      simple McGhee-von Hippel model, nor fit satisfactorily by the inclusion of a
      cooperativity parameter. Instead, the interaction appeared to be well described
      by Crothers' allosteric model, in which the higher affinity of the protein for
      one conformational form of the DNA drives an allosteric transition of the DNA to
      the conformational form with higher affinity (form 2). At 214 mM Na(+), the
      observed affinity K for an isolated site on unmodified T4 bacteriophage DNA in
      the form 2 conformation is 4.5 x 10(7) M(-1). The binding constant for an
      isolated site on DNA in the conformation with lower affinity, form 1, appears to
      be about 10-fold lower. Binding affinity is dependent on ion concentration: the
      magnitude of K is about 10-fold higher at 14 mM (5.9 x 10(8) M(-1) for form 2
      DNA) than at 214 mM Na(+) concentration.

PMID- 15558657
TI  - Fixation protocols for subcellular imaging by synchrotron-based Fourier transform
      infrared microspectroscopy.
AB  - Synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy is a
      powerful bioanalytical technique for the simultaneous analysis of lipids,
      proteins, carbohydrates, and a variety of phosphorylated molecules within intact
      cells. SR-FTIR microspectroscopy can be used in the imaging mode to generate
      biospectroscopic maps of the distribution and intensity profiles of subcellular
      biomolecular domains at diffraction-limited spatial resolution. However, the
      acquisition of highly spatially resolved IR images of cells is not only a
      function of instrumental parameters (source brightness, sampling aperture size)
      but also the cell preparation method employed. Additionally, for the IR data to
      be biochemically relevant the cells must be preserved in a life-like state
      without introducing artefacts. In the present study we demonstrate, for the first
      time, the differences in biomolecular localizations observed in SR-FTIR images of
      cells fixed by formalin, formalin-critical point drying (CPD), and glutaraldehyde
      osmium tetroxide-CPD, using the PC-3 prostate cancer cell line. We compare these
      SR-FTIR images of fixed cells to unfixed cells. The influence of chemical
      fixatives on the IR spectrum is discussed in addition to the biological
      significance of the observed localizations. Our experiments reveal that formalin
      fixation at low concentration preserves lipid, phosphate, and protein components
      without significantly influencing the IR spectrum of the cell.

PMID- 15558658
TI  - O-acylation of hydroxyproline residues: effect on peptide-bond isomerization and
      collagen stability.
AB  - In collagen, strands of the sequence XaaYaaGly form a triple-helical structure.
      The Yaa residue is often (2S,4R)-4-hydroxyproline (Hyp). The inductive effect of
      the hydroxyl group of Hyp residues greatly increases collagen stability. Here,
      electron withdrawal by the hydroxyl group in Hyp and its 4S diastereomer (hyp) is
      increased by the addition of an acetyl group or trifluoroacetyl group. The
      crystalline structures of AcHyp[C(O)CH3]OMe and Achyp[C(O)CH3]OMe are similar to
      those of AcHypOMe and AcProOMe, respectively. The O-acylation of AcHypOMe and
      AchypOMe increases the 13C chemical shift of its Cgamma atom: AcHyp[C(O)CF3]OMe
      congruent with Achyp[C(O)CF3]OMe > AcHyp[C(O)CH3]OMe congruent with
      Achyp[C(O)CH3]OMe > or = AcHypOMe congruent with AchypOMe. This increased
      inductive effect is not apparent in the thermodynamics or kinetics of amide bond
      isomerization. Despite apparently unfavorable steric interactions,
      (ProHypGly)(10), which is O-acylated with 10 acetyl groups, forms a triple helix
      that has intermediate stability: (ProHypGly)(10) > {ProHyp[C(O)CH3]Gly}(10) >>
      (ProProGly)(10). Thus, the benefit to collagen stability endowed by the hydroxyl
      group of Hyp residues is largely retained by an acetoxyl group.

PMID- 15558659
TI  - Discrete metal-based catalysts for the copolymerization of CO2 and epoxides:
      discovery, reactivity, optimization, and mechanism.
AB  - Most synthetic polymers are made from petroleum feedstocks. Given the non
      renewable nature of these materials, there is increasing interest in developing
      routes to polymeric materials from renewable resources. In addition, there is a
      growing demand for biodegradable polymeric materials. Polycarbonates made from
      CO(2) and epoxides have the potential to meet these goals. Since the discovery of
      catalysts for the copolymerization of CO(2) and epoxides in the late 1960's by
      Inoue, a significant amount of research has been directed toward the development
      of catalysts of improved activity and selectivity. Reviewed here are well-defined
      catalysts for epoxide-CO(2) copolymerization and related reactions.

PMID- 15558660
TI  - Probing NMR parameters, structure and dynamics of 5-nitroimidazole derivatives.
      Density functional study of prototypical radiosensitizers.
AB  - The 15N chemical shifts of metronidazole (1), secnidazole (2), nimorazole (3) and
      tinidazole (4), radiosensitizers based on the 5-nitroimidazole motif, are
      reported. A detailed computational study of 1 is presented, calling special
      attention to the performance of various theoretical methods in reproducing the
      13C and 15N data observed in solution. The most sophisticated approach involves
      density functional-based Car-Parrinello molecular dynamics simulations (CPMD) of
      1 in aqueous solution (BP86 level) and averaging chemical shifts over snapshots
      from the trajectory. In the NMR calculations for these snapshots (performed at
      the B3LYP level), a small number of discrete water molecules are retained, and
      the remaining bulk solution effects are included via a polarizable continuum
      model (PCM). A similarly good accord with experiment is obtained from much less
      involved, static geometry optimization and NMR computation of pristine 1
      employing a PCM approach. Solvent effects on delta(15N), which are of the order
      of up to 20 ppm, are not due to changes in geometric parameters upon solvation,
      but arise from the direct response of the electronic wavefunction to the presence
      of the solvent, which can be represented by discrete molecules and/or the
      dielectric bulk.

PMID- 15558661
TI  - Large lattice responses in a mixed-valence Prussian blue analogue owing to
      electronic and spin transitions induced by X-ray irradiation.

PMID- 15558662
TI  - cRGD-functionalized polymer micelles for targeted doxorubicin delivery.

PMID- 15558663
TI  - Solid-phase synthesis of styryl dyes and their application as amyloid sensors.

PMID- 15558664
TI  - Improving quantum efficiencies of siloles and silole-derived butadiene
      chromophores through structural tuning.

PMID- 15558665
TI  - A reductive-aggregation route to [Mn12O12(OMe)2(O2CPh)16(H2O)2]2- single-molecule
      magnets related to the [Mn12] family.

PMID- 15558666
TI  - A purely organic molecular metal based on a hydrogen-bonded charge-transfer
      complex: crystal structure and electronic properties of TTF-imidazole-p
      chloranil.

PMID- 15558667
TI  - Photoswitchable organic nanoparticles and a polymer film employing
      multifunctional molecules with enhanced fluorescence emission and bistable
      photochromism.

PMID- 15558668
TI  - Optimization of "wired" enzyme O2-electroreduction catalyst compositions by
      scanning electrochemical microscopy.

PMID- 15558669
TI  - Quality control of Harpagophytum procumbens and its related phytopharmaceutical
      products by means of NIR-FT-Raman spectroscopy.
AB  - NIR-FT-Raman spectroscopy was used for identification and quantification of
      harpagoside in secondary roots of Harpagophytum procumbens as well as in related
      phytopharmaceutical products, e.g., ethanolic extracts and tablets. Applied Raman
      mappings reveal the spatial distribution of this valuable iridoid glycoside
      within the different samples. The same technique can be used for quality control
      purposes beginning from the plant to its final products. Based on the obtained
      spectral data and reference HPLC values of harpagoside, a reliable multivariate
      calibration model was developed.

PMID- 15558670
TI  - Ferromagnetic interaction in mu1,3-cyanamido-derived copper(II) cryptates.
AB  - The reaction of dinuclear copper(II) cryptates with calcium cyanamide, CaNCN, and
      sodium dicyanamide, Na[N(CN)(2)] results in dinuclear compounds of formulae
      [Cu(2)(HNCN)(R3Bm)](ClO(4))(3) (1), [Cu(2)(dca)(R3Bm)](ClO(4))(3)4H(2)O (2), and
      [Cu(2)(NCNCONH(2))(R3Bm)](CF(3)SO(3))(3) (3), in which
      R3Bm=N[(CH(2))(2)NHCH(2)(C(6)H(4)-m)CH(2)NH(CH(2))(2)](3)N and dca=dicyanamido
      ligand (NCNCN(-)). The X-ray diffraction analysis reveals for both 1 and 3 a
      dinuclear entity in which the copper atoms are bridged by means of the -NCN-
      unit. The molar magnetic susceptibility measurements of 1-3 in the 2-300 K range
      indicate ferromagnetic coupling. The calculated J values, by using theoretical
      methods based on density functional theory (DFT) are in excellent agreement with
      the experimental data. Catalytic hydration of a nitrile to an amide functional
      group is assumed responsible for the formation of 3 from a mu(1,3)-dicyanamido
      ligand.

PMID- 15558671
TI  - Chemiluminescent analysis of the antioxidant and immunomodulation effects of
      several psychotropic drugs on peritoneal macrophages.
AB  - The present study describes the application of several chemiluminescent (CL)
      methods for evaluation of antioxidant and immunomodulation effects of
      psychotropic drugs upon phagocytes: KO2-induced luminal-dependent CL for
      detection of superoxide anion radicals in a pure chemical system; PMA- and A23187
      induced CL of peritoneal macrophages for detection of free radicals in cell
      suspension; and CL, produced by the luciferase-catalyzed luciferin + ATP
      reaction, for evaluation of cell viability before and after drug application.
      These methods provide also a way to investigate the location of drug action. It
      was found that the psychotropic drugs in fluence the 'oxidative burst' of
      macrophages through two mechanisms: by expression of drug antioxidant properties
      and/or by a direct immunomodulation effect.

PMID- 15558672
TI  - Chemiluminescent and bioluminescent assays as innovative prospects for mycotoxin
      determination in food and feed.
AB  - Mycotoxin contamination of food and feedstuffs is among the top priorities for
      human and animal safety. The currently used techniques for mycotoxin
      determination, either chromatography or ELISA, are unsuitable for routine in
      field assessment. There is an urgent need for other accurate, simple and cost
      effective techniques that can be used as a screening tool for a rapid estimation
      of mycotoxin contamination in commodity lots. This paper reviews the literature
      on the use of chemiluminescence (CL) and bioluminescence (BL) assays for direct
      or indirect mycotoxin assessment. The chemiluminescence immunoassays, adenosine
      triphosphate (ATP) bioluminescence and bioassays are reviewed and their
      advantages and limitations discussed. These techniques used in food testing and
      the pharmaceutical industry offer promise as rapid techniques for mycotoxin
      determination. Chemiluminescence and bioluminescence bioassays are the most
      innovative alternatives to the conventional techniques used for mycotoxin
      determination in food and feed.

PMID- 15558675
TI  - Pyrrole syntheses by multicomponent coupling reactions.

PMID- 15558676
TI  - Controlled microwave heating in modern organic synthesis.
AB  - Although fire is now rarely used in synthetic chemistry, it was not until Robert
      Bunsen invented the burner in 1855 that the energy from this heat source could be
      applied to a reaction vessel in a focused manner. The Bunsen burner was later
      superseded by the isomantle, oil bath, or hot plate as a source for applying heat
      to a chemical reaction. In the past few years, heating and driving chemical
      reactions by microwave energy has been an increasingly popular theme in the
      scientific community. This nonclassical heating technique is slowly moving from a
      laboratory curiosity to an established technique that is heavily used in both
      academia and industry. The efficiency of "microwave flash heating" in
      dramatically reducing reaction times (from days and hours to minutes and seconds)
      is just one of the many advantages. This Review highlights recent applications of
      controlled microwave heating in modern organic synthesis, and discusses some of
      the underlying phenomena and issues involved.

PMID- 15558677
TI  - Chemical control of valence tautomerism of nickel(II) semiquinone and nickel(III)
      catecholate states.

PMID- 15558678
TI  - Metallic nanomagnets randomly dispersed in spherical colloids: toward a universal
      route for the preparation of colloidal composites containing nanoparticles.

PMID- 15558679
TI  - Dipeptides as microporous materials.

PMID- 15558680
TI  - Pd-catalyzed amination of nucleoside arylsulfonates to yield N6-aryl-2,6
      diaminopurine nucleosides.

PMID- 15558681
TI  - In situ magnetic resonance investigation of styrene oxidation over TS-1 zeolites.

PMID- 15558682
TI  - A bis(thiophosphinoyl)methanediide palladium complex: coordinated dianion or
      nucleophilic carbene complex?

PMID- 15558684
TI  - Metabolic studies on the total phenolic acids from the roots of Salvia
      miltiorrhiza in rats.
AB  - Phenolic acids are the main active constituents of Salvia miltiorrhiza Bunge. The
      metabolism of total phenolic acids from the roots of Salvia miltiorrhiza in rats
      was investigated. A sample preparation method combining the solid-phase
      extraction with liquid-liquid extraction was established to separate metabolites
      from the biological matrix. HPLC-UV and HPLC-MS methods were employed to analyze
      the metabolites. Five metabolites (M1-M5) were identified by HPLC-MS analysis and
      comparison with those of the reference standards. The fi ve metabolites were
      characterized as danshensu (M1), caffeic acid (M2), ferulic acid (M3), isoferulic
      acid (M4) and methylized ferulic acid (M5), respectively. The possible metabolic
      pathway of the phenolic acids is proposed.

PMID- 15558685
TI  - Successful management of discovered pH dependence in vancomycin recovery studies:
      novel HPLC method for microdialysis and plasma samples.
AB  - Vancomycin is a glycopeptide antibiotic approved for the treatment of serious
      infections or patients allergic to beta-lactams. A rapid HPLC assay using UV
      detection for the determination in microdialysate and human plasma was developed.
      After sample preparation, using methanol and trichloroacetic acid for plasma and
      water for microdialysate, 20 microL were injected and separated on a RP(18)
      column. Overall, the assay exhibited good precision and accuracy. The diffusion
      properties of vancomycin investigated in in vitro microdialysis experiments
      revealed an unfavourable concentration dependence avertable by keeping a constant
      pH using phosphate buffer as perfusate. The mean relative recoveries were 27.8%
      [coefficient of variation (CV) 11.1%] and 33.2% (CV 8.3%) for retrodialysis and
      recovery experiments, respectively. Following characterization of vancomycin in
      in vitro microdialysis, the developed setting is suitable for application in (pre
      )clinical studies.

PMID- 15558686
TI  - Separation of peroxidation products of diacyl-phosphatidylcholines by reversed
      phase liquid chromatography-mass spectrometry.
AB  - Lipid peroxidation process has attracted much attention due to the growing
      evidence of its involvement in the pathogenesis of age-related diseases. The
      monitoring of the lipid peroxidation products in phospholipids, formed under
      oxidative stress conditions, may provide new markers for oxidative stress
      signaling and for disease states, giving new insights in the pathogenesis
      process. Reversed-phase liquid chromatographic method coupled to mass
      spectrometry was developed for the separation of oxidized glycero
      phosphatidylcholine (GPC) peroxidation products formed by the Fenton reaction
      that mimic in vivo oxidative stress conditions. The LC-MS conditions were applied
      for the separation of peroxidation products of oleoyl- (POPC), lineloyl- (PLPC)
      and arachidonoyl-palmitoyl phosphatidylcholine (PAPC). The peroxidation products
      separated included products resulting from the insertion of oxygen atoms in the
      sn-2 chain (long-chain), and products with the sn-2 chain shortened resulting
      from cleavage of oxygen-centered radicals (short-chain). Among long-chain
      products were the keto, hydroxy, hydroperoxide and poly-hydroxy derivatives,
      while short-chain products included dicarboxylic acids, aldehydes and hydroxy
      aldehydes. Separation of long-chain products formed in each phosphatidylcholine
      was observed, and the reconstructed ion chromatogram of each ion showed an
      increase in the number of peaks with the increase in the number of oxygen atoms
      inserted into the phospholipid. Separation of short-chain products took place
      according to the functional group present at the sn-2 moiety that allowed the
      elution of dicarboxylic acids distinct from aldehydes. Separation between
      isomeric structures that were present in short- and long-chain products was also
      achieved.

PMID- 15558687
TI  - Study on the interaction between protein and Eu(III)-chlorotetracycline complex
      and the determination of protein using the fluorimetric method.
AB  - Chlorotetracycline (CTC) can react with europium ions Eu3+, and the complex emits
      the intrinsic fluorescence of Eu3+. The intensity is greatly enhanced by proteins
      and this forms the basis of a new fluorimetric method for determination of
      protein. Further research indicates that under optimum conditions, the enhanced
      intensity of fluorescence is in proportion to the concentration of proteins, in
      the range 2.0 x 10(-7)-1.0 x 10(-5) g/mL for bovine serum albumin (BSA) (linear
      equation, I(f) = 34.35933 + 11.54467 x 10(6)C)(r = 0.99895) and 8.0 x 10(-7)-1.0
      x 10(-5) g/mL for human serum albumin (HSA) (linear equation, I(f) = 76.58881 +
      5.3569 x 10(6)C) (r = 0.99283). Detection limits (S/N = 3) were 8.9 x 10(-9) g/mL
      for BSA and 3.3 x 10(-8) g/mL for HSA. In an assay for BSA in calf serum, this
      method gave a value close to that determined by the UV spectrophotometric method.

PMID- 15558689
TI  - Luminescence literature.

PMID- 15558690
TI  - Asymmetric synthesis of highly substituted beta-lactones by nucleophile-catalyzed
      [2+2] cycloadditions of disubstituted ketenes with aldehydes.

PMID- 15558691
TI  - Large-scale synthesis of micrometer-scale single-crystalline Au plates of
      nanometer thickness by a wet-chemical route.

PMID- 15558692
TI  - High-mobility air-stable n-type semiconductors with processing versatility:
      dicyanoperylene-3,4:9,10-bis(dicarboximides).

PMID- 15558693
TI  - An iridium difluoroketene complex: synthesis and isolation.

PMID- 15558694
TI  - Polymer-monomer pairs as a reaction system for the synthesis of magnetic Fe3O4
      polymer hybrid hollow nanospheres.

PMID- 15558695
TI  - Determination of urinary S-sulphocysteine, xanthine and hypoxanthine by liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - Molybdenum cofactor and isolated sulphite oxidase deficiencies are two related
      rare autosomal recessive diseases characterized by severe neurological
      abnormalities, dislocated lens and mental retardation. Determination of three
      biochemical markers S-sulphocysteine (SSC), xanthine (XAN) and hypoxanthine
      (HXAN) in urine is essential for a definitive diagnosis and identification of the
      exact defect. We developed a rapid liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method for the analysis of SSC, XAN and HXAN in urine. The analysis
      was carried out in the negative-ion selected-reaction monitoring mode. The
      turnaround time for the assay was 7 min. Linear calibration curves for the three
      biomarkers were obtained in the range of 12-480 micromol/L. The intra- and inter
      day assay variations were <2.5%. Mean recoveries of SSC, XAN and HXAN added to
      urine at two significantly different concentrations were in the range 94.3
      107.3%. At a normal SSC urine excretion value of 3.2 micromol/mmol creatinine,
      the signal-to-noise ratio was 337:1. This stable isotope dilution LC-MS/MS method
      is specific, rapid and simple, and provides definitive diagnosis for molybdenum
      cofactor and isolated sulphite oxidase deficiencies in very small volumes of
      urine. We have identified seven new cases of isolated sulphite oxidase deficiency
      from four Saudi families and one Sudanese family.

PMID- 15558696
TI  - Non-parametric paired two-sample tests for censored survival data incorporating
      longitudinal covariate information.
AB  - In this manuscript, we present non-parametric two-sample tests for paired
      censored survival data incorporating longitudinal covariate information. These
      tests take advantage of information collected at baseline and post-baseline to
      provide efficiency gains when censoring is uninformative. Additionally, these
      methods adjust for potential bias from informative censoring that is captured by
      the baseline and longitudinal covariates. Finite sample properties are
      investigated with simulation, and we illustrate methodology with an example from
      the Early Treatment Diabetic Retinopathy Study.

PMID- 15558697
TI  - A three-level model for binary time-series data: the effects of air pollution on
      school absences in the Southern California Children's Health Study.
AB  - A three-level model is proposed to simultaneously examine the effects of daily
      exposure to air pollution and individual risk factors on health outcomes without
      aggregating over subjects or time. We used a logistic transition model with
      random effects to take into account heterogeneity and overdispersion of the
      observations. A distributed lag structure for pollution has been included,
      assuming that the event on day t for a subject depends on the levels of air
      pollution for several preceding days. We illustrate this proposed model via
      detailed analysis of the effect of air pollution on school absenteeism based on
      data from the Southern California Children's Health Study.

PMID- 15558698
TI  - Linear equations with random variables.
AB  - A system of linear equations is presented where the unknowns are unobserved
      values of random variables. A maximum likelihood estimator assuming a
      multivariate normal distribution and a non-parametric proportional allotment
      estimator are proposed for the unobserved values of the random variables and for
      their means. Both estimators can be computed by simple iterative procedures and
      are shown to perform similarly. The methods are illustrated with data from a
      national nutrition survey in Japan.

PMID- 15558699
TI  - Comparing the concentration curves directly in a pharmacokinetics,
      bioavailability/bioequivalence study.
AB  - In a traditional pharmacokinetics (PK), bioavailability (BA) /bioequivalence (BE)
      study, the same number of time points and sampling times are used for each
      subject. Often, an indirect inference is then made on some PK parameters such as
      area under the plasma concentration curve (AUC), maximum plasma concentration
      (C(max)), time to maximum plasma concentration (T(max)) or half-life. However,
      since these PK parameters are summarized from repeated measurements, a lot of
      information can be lost. The indirect inferences on some PK parameters are not
      always accurate. Taking the repeated measurements of the concentration curve into
      consideration, a functional linear model has been developed to compare
      concentration curves directly instead of the PK parameters. Considering the
      nature of repeated measurements, a multiple testing procedure is proposed to
      assess the equality of two concentration curves. A real data set is used to
      demonstrate the proposed procedure.

PMID- 15558700
TI  - Simultaneous determination of phytoestrogens in different medicinal parts of
      Sophora japonica L. by capillary electrophoresis with electrochemical detection.
AB  - A high-performance capillary electrophoresis with electrochemical detection (CE
      ED) method has been developed for the determination of phytoestrogens from the
      pericarps and seeds of Sophora japonica L. in this work. Genistin, genistein,
      rutin, kaempferol and quercetin are important bioactive constituents in these
      plants. The effects of several factors such as the acidity and concentration of
      running buffer, the separation voltage, the applied potential and the injection
      time on the CE-ED procedure were investigated. Under the optimum conditions, the
      five analytes could be well separated within 18 min in a 75 cm length capillary
      (i.d. 25 microm) at the separation voltage of 16 kV in a 50 mmol L(-1) borax
      running buffer (pH 9.0). A 300 microm diameter carbon disk electrode was used as
      the working electrode positioned carefully opposite the outlet of the capillary
      in a wall-jet configuration at the potential of +950 mV (vs SCE). Detection
      limits (S/N = 3) ranged from 1.1 x 10(-7) to 2.8 x 10(-7) g mL(-1) for all fi ve
      analytes. This method was successfully used to analyse dried Flos sophorae
      immaturus, pericarps and seeds of dried Fructus sophorae after a relatively
      simple extraction procedure, and the assay results were satisfactory.

PMID- 15558701
TI  - Transient leukemia in newborns with Down syndrome.
AB  - Children with Down syndrome (DS) have a 10- to 20-fold increased risk of
      developing leukemia, particularly acute megakaryocytic leukemia. Newborns with DS
      or trisomy 21 mosaicism may exhibit a particularly unique form of leukemia that
      historically has been associated with a high rate of spontaneous remission. This
      transient leukemia (TL) has been shown to be a clonal proliferation of blast
      cells exhibiting megakaryocytic features. Its true incidence remains to be
      determined. At presentation, many infants are clinically well with only an
      incidental finding of abnormal blood counts and circulating blasts in the
      peripheral blood. However, in approximately 20% of cases, the disease is severe
      and life-threatening, manifesting as hydrops faetalis, multiple effusions, and
      liver or multi-organ system failure resulting in death. Of those children who
      enter a spontaneous remission, 13-33% have been found to develop subsequent acute
      megakaryoblastic leukemia, usually within the first 3 years of life, which if
      left untreated is fatal. This unique TL of the DS newborn has been the subject of
      recent clinical cooperative group trials as well as many biological and genetic
      research efforts. We summarize here the known clinical, biological, and
      cytogenetic features of TL associated with DS.

PMID- 15558702
TI  - Experience with chemoreduction and focal therapy for intraocular retinoblastoma
      in a developing country.
AB  - BACKGROUND: Chemoreduction is used for the treatment of retinoblastoma in
      industrialized nations; however, there are fewer data from developing countries.
      Before the implementation of this program, radiotherapy was used in almost all
      preserved eyes. METHODS: Retrospective evaluation from 1995 to 2001 at the
      Hospital Garrahan (Argentina). Carboplatin 18.7 mg/kg/day 1 and vincristine (0.05
      mg/kg/day 1) were offered to patients with Reese-Ellsworth (RE) groups I-III and
      all unilateral cases. Etoposide (3.3 mg/kg/day 1 and 2) was added for groups IV
      and V. The number of cycles was tailored according to response. RESULTS: Fifty
      eight patients (78 eyes) were evaluated (39 bilateral, 19 unilateral). With a
      median follow-up of 47 months, 40 patients had unilateral enucleation, 14 were
      not enucleated, and 4 had bilateral enucleation. Nineteen patients had unilateral
      initial enucleation. Eye preservation at 5 years was: RE groups I-III (n = 24
      eyes), 0.9 (SE: 0.095) IV-V (n = 54), 0.45 (SE 0.07). Patients received a median
      of four cycles of chemotherapy. Acute toxicity was mild. External beam
      radiotherapy was avoided in 41% of eyes with groups I-III. Etoposide was avoided
      in 24 patients. Two patients died of metastasis. No secondary malignancy
      occurred. CONCLUSIONS: Compared to our previous experience, eye preservation was
      better and even though less radiotherapy was used, it was prescribed more often
      than currently recommended in eyes with less advanced disease because of limited
      availability of sophisticated local therapy.

PMID- 15558703
TI  - RNA expression analysis of a congenital intracranial teratoma.
AB  - Congenital intracranial tumors are extremely rare and account only for 0.5%-1.5%
      of brain tumors in children. We report a large intrauterine congenital teratoma
      in a female fetus at gestation weeks 37, which was diagnosed by detecting the
      tumor and associated craniomegaly with ultrasonography (US) and magnetic
      resonance (MR) imaging. The tumor had replaced the cerebral hemispheres and
      produced prenatal manifestations. Pathologic examination showed an immature
      teratoma, which was differentiated from all three germ layers. Microarray
      analysis revealed upregulation of ten genes and downregulation of three genes, as
      well as upregulation of 41 genes of ribosomal proteins in teratoma cells,
      compared to normal brain tissue of the patient. The data from the microarray
      analysis offer not only the potential to help define disease pathogenesis but may
      also provide clues to identify potential molecular therapeutic targets.

PMID- 15558704
TI  - Robotically guided radiosurgery for children.
AB  - BACKGROUND: A robotically guided linear accelerator has recently been developed
      which provides frameless radiosurgery with high precision. Potential advantages
      for the pediatric population include the avoidance of the cognitive decline
      associated with whole brain radiotherapy, the ability to treat young children
      with thin skulls unsuitable for frame-based methods, and the possible avoidance
      of general anesthesia. We report our experience with this system (the
      "Cyberknife") in the treatment of 21 children. PROCEDURES: Cyberknife
      radiosurgery was performed on 38 occasions for 21 patients, age ranging from 8
      months to 16 years (7.0 +/- 5.1 years), with tumors considered unresectable.
      Three had pilocytic astrocytomas, two had anaplastic astrocytomas, three had
      ependymomas (two anaplastic), four had medulloblastomas, three had atypical
      teratoid/rhabdoid tumors, three had craniopharyngiomas, and three had other
      pathologies. The mean target volume was 10.7 +/- 20 cm(3), mean marginal dose was
      18.8 +/- 8.1 Gy, and mean follow-up is 18 +/- 11 months. Twenty-seven (71%) of
      the treatments were single-shot and eight (38%) patients did not require general
      anesthesia. RESULTS: Local control was achieved in the patients with pilocytic
      and anaplastic astrocytoma, three of the patients with medulloblastoma, and the
      three with craniopharyngioma, but not for those with ependymoma. Two of the
      patients with rhabdoid tumors are alive 16 and 35 months after this diagnosis.
      There have been no procedure related deaths or complications. CONCLUSION:
      Cyberknife radiosurgery can be used to achieve local control for some children
      with CNS tumors without the need for rigid head fixation.

PMID- 15558705
TI  - Pediatric nasopharyngeal carcinoma: better prognosis and increased c-Kit
      expression as compared to adults.
AB  - INTRODUCTION: Nasopharyngeal carcinoma (NPC) in children is distinguishable from
      the adult form by its close association with Epstein-Barr virus (EBV) infection,
      a higher rate of undifferentiated histology, and a greater incidence of advanced
      locoregional disease. PATIENTS AND METHODS: Sixteen NPC patients, < or =20 years
      of age were identified from our 1976-2001 tumor registry records. Clinical stage,
      treatment, recurrence, and survival were evaluated. Sections were stained by
      immunohistochemistry for p53, Bcl-2, Ki67, and c-Kit and by in situ hybridization
      for EBER. Obtained data were compared to 32 adult patients. All patients had
      undifferentiated or non-keratinizing NPC. RESULTS: EBER was positive in 100% of
      children, compared to 90% of adults. Comparing children to adults, median Ki67
      index was 49% and 30%, p53 positive tumors were 69% and 94%, positive Bcl-2 was
      63% and 72%, and positive c-Kit was 88% and 28%, respectively. CONCLUSION: No
      parameter had significant predictive values for survival, although c-Kit
      expression had a trend for better prognosis in the pediatric group. By univariate
      analysis of all 48 cases, positive c-Kit was associated with better survival (P =
      0.029), largely due to the better survival of the pediatric group. By
      multivariate analysis, increased stage (P = 0.006) and older age (P = 0.044)
      correlated with worse prognosis.

PMID- 15558706
TI  - Surgical management of pelvic sarcomas in children.
AB  - Pelvic sarcomas are uncommon in childhood. Survival rates of children with pelvic
      sarcomas have shown significant improvements over the past few decades.
      Correspondingly, there has been an increase in limb-sparing surgical procedures
      being performed in these children. This could be attributed in part to the newer
      generation imaging techniques, wider armamentarium of surgical techniques of
      reconstruction, and limb-salvage and advances in neo-adjuvant chemotherapy and
      radiotherapy. Reconstruction after resection of pelvic sarcomas while preserving
      function of the hip and limb can be extremely challenging especially in children
      where there are issues of growth potential and limb-length discrepancies. This
      article focuses on the presentation and epidemiology of different types of pelvic
      sarcomas in children, the current state-of-art of imaging and surgical management
      of children with pelvic sarcomas.

PMID- 15558707
TI  - Immune reconstitution after childhood acute lymphoblastic leukemia is most
      severely affected in the high risk group.
AB  - OBJECTIVE: The aim was to examine the immune reconstitution after current
      chemotherapy for childhood ALL, with a special focus on finding immunologic
      variables that predict a poor immune response to vaccinations. PROCEDURE: In a
      cross-sectional study of 31 children after treatment with the NOPHO ALL-1992
      protocol peripheral blood lymphocyte subsets, T- and B-cell function in vitro and
      serum immunoglobulins (Ig) were measured. All patients were examined once, at 1
      or at 6 months after cessation of chemotherapy, immediately before vaccination
      with DT and Hib. RESULTS: Lymphocytes, T-cells, and CD4+ T-cells were low at 6
      months after treatment. Naive T-cell subsets were more reduced than memory
      subsets. In the high risk (HR) ALL group, CD8+ T-cells were reduced at 6 months.
      NK-cells were low at 1 month, but normal at 6 months; however, the CD3+CD56+
      (NKT) subset was reduced at both time points. Total B-cell number was low at 1
      month, but normal at 6 months. A relative increase of CD5+ B-cells (B-1 cells)
      was evident, particularly in the HR group. Antigen-independent T- and B-cell
      function in vitro were affected at 1 month, but virtually normalized at 6 months.
      Serum IgM level was decreased at 1 month and IgG3 level was increased at 1 and 6
      months. CONCLUSIONS: This study shows that immune reconstitution after childhood
      ALL is slower than previously reported and emphasizes the influence of treatment
      intensity. The most intensively treated patients still have persistent
      abnormalities in T-, B-, and NK-cell subsets at 6 months post therapy and show a
      poor response to immunization with T-cell dependent antigens. In the HR group,
      routine re-immunizations before this time point are of limited benefit, and the
      effect of repeated vaccinations should be evaluated.

PMID- 15558708
TI  - Curiouser and curiouser.

PMID- 15558709
TI  - The utility of prior information and stratification for parameter estimation with
      two screening tests but no gold standard.
AB  - When a gold standard screening or diagnostic test is not routinely available, it
      is common to apply two different imperfect tests to subjects from a study
      population. There is a considerable literature on estimating relevant parameters
      from the resultant data. In the situation that test sensitivities and
      specificities are unknown, several inferential strategies have been proposed. One
      suggestion is to use rough knowledge about the unknown test characteristics as
      prior information in a Bayesian analysis. Another suggestion is to obtain the
      statistical advantage of an identified model by splitting the population into two
      strata with differing disease prevalences. There is some division of opinion in
      the epidemiological literature on the relative merits of these two approaches.
      This article aims to shed light on the issue, by applying some recently developed
      theory on the performance of Bayesian inference in non-identified statistical
      models.

PMID- 15558710
TI  - Probing Prometheus: fat fueling the fire?

PMID- 15558711
TI  - Mesenchymal stem cells: an alternative source of hepatocytes?

PMID- 15558712
TI  - Treatment with pegylated interferon and ribavarin in HCV infection with genotype
      2 or 3 for 14 weeks: a pilot study.
AB  - The aim of this study was to determine the efficacy of 14 weeks of treatment in
      patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early
      virological response (EVR). In a noncontrolled multicenter trial, 122 treatment
      naive patients received 1.5 mug/kg pegylated interferon alfa-2b subcutaneously
      once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was
      stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks
      4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary
      end point was sustained virological response (SVR), defined as undetectable HCV
      RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and
      received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks.
      SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15
      of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100
      of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was
      achieved more frequently among genotype 3a patients with low viral load compared
      with high viral load (98% vs. 79%; P = .019). Logistic regression analysis showed
      that absence of bridging fibrosis/cirrhosis was the only independent predictor of
      SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR
      after 14 weeks of treatment. The results need to be confirmed in a randomized,
      controlled study before this treatment approach can be recommended, particularly
      for patients with genotype 3 and high viral load or severe fibrosis.

PMID- 15558713
TI  - Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson
      syndrome.
AB  - Two siblings from a consanguineous family presented with a poikiloderma of limbs
      and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and
      neutrophil dysfunction with impairment of the respiratory burst and bacterial
      killing resulted in frequent respiratory tract infections. A bronchocentric
      granulomatous pneumonia was a fatal complication. The clinical presentation is
      consistent with Clericuzio type poikiloderma with neutropenia. Literature review
      identified several additional probable patients. Genetic linkage analysis
      excluded the locus of the RECQL4 gene, mutations in which have been described in
      some patients with the Rothmund-Thomson poikiloderma syndrome. This report
      confirms the clinical and genetic identity of the Clericuzio type of poikiloderma
      with neutropenia syndrome.

PMID- 15558714
TI  - Novel exonic mu-opioid receptor gene (OPRM1) polymorphisms not associated with
      opioid dependence.
AB  - The mu-opioid receptor (MOR) mediates reward and dependence associated with
      opioids and other commonly abused substances. Variability in the MOR gene, OPRM1,
      may influence risk for opioid dependence. In this study, associations between two
      single nucleotide polymorphisms (SNPs), dbSNP rs540825 and dbSNP rs562859, and
      opioid dependence were investigated. The two SNPs are located in the protein
      coding region of the novel exon X of an alternative splice variant of OPRM1, and
      can be detected using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) methods. Genotyping at the two SNPs was performed for 170
      severe opioid dependent individuals and 128 carefully screened controls. Although
      no differences were found between cases and controls, there were significant
      prevalence differences between African-American (AA) subjects and European
      American (EA) subjects for SNP 540825 allele and genotype frequencies. The 540825
      and 562859 polymorphisms were found to be in complete linkage disequilibrium (LD)
      for both ethnic groups, and LD existed between the 562859 SNP and the A(-1320)G
      SNP in the promoter region of OPRM1 in AAs, based on genotyping data previously
      carried out on the same subjects. LD between these two markers, separated by 55
      kb, links the entire distance studied in this project. The results indicate that
      polymorphisms in the novel splice variant are not associated with opioid
      dependence, but are in LD with other polymorphisms in OPRM1.

PMID- 15558715
TI  - A genome-wide search for risk genes using homozygosity mapping and microarrays
      with 1,494 single-nucleotide polymorphisms in 22 eastern Cuban families with
      bipolar disorder.
AB  - Homozygosity mapping is a very powerful method for finding rare recessive disease
      genes in monogenic disorders and may also be useful for locating risk genes in
      complex disorders, late onset disorders where parents often are not available,
      and for rare phenotypic subgroups. In the present study, homozygosity mapping was
      applied to 24 persons with bipolar disorder from 22 inbred families. The families
      were selected irrespective of whether other affected family members were present
      or not. A genome wide screen using genotypes from only a single affected person
      in each family was performed using the AFFYMETRIX GeneChip HuSNP Mapping Assay,
      which contains 1,494 single nucleotide polymorphisms. At chromosome 17q24-q25 a
      parametric multipoint LOD score of 1.96 was found at WIAF-2407 and WIAF-2405.
      When analyzing 19 additional microsatellite markers on chromosome 17q the maximum
      parametric multipoint LOD score was 2.08, 1.5 cM proximal to D17S668. The present
      study replicates a recent significant linkage finding.

PMID- 15558716
TI  - No association of a non-synonymous PLAU polymorphism with Alzheimer's disease and
      disease-related traits.
AB  - A 30 cM broad genomic region on the long arm of chromosome 10 at 80 cM shows
      significant and consistent linkage with AD and with plasma concentration of the
      beta-amyloid peptide 1-42 (Abeta42). The PLAU gene, which is involved in the
      production and degradation of Abeta42, maps to that region and is therefore a
      strong positional candidate for association with sporadic AD. We analyzed the non
      synonymous single nucleotide polymorphism (SNP) rs2227564 in two independent case
      control series from Switzerland and Greece and investigated the influence of this
      SNP on cognition in elderly individuals. Because PLAU modulates the cleavage of
      the amyloid precursor protein (APP) and the degradation of Abeta, we also
      determined the levels of Abeta in the brain, plasma and in the cerebrospinal
      fluid (CSF). We found no evidence for association of this SNP with AD or with AD
      related traits such as beta-amyloid load in the medial temporal lobe or Abeta42
      concentration in the CSF and in plasma. Our findings do not support a major role
      of PLAU polymorphisms as susceptibility factors for AD and suggest that large
      scale association studies which combine genetic information from populations with
      similar genetic background might prevent the generation of spurious associations.
      Although PLAU may be pathophysiologially related to AD, the contribution of
      common genetic variants of this gene to the risk for developing AD is likely to
      be low.

PMID- 15558717
TI  - Expression of alpha5 nicotinic acetylcholine receptor subunit mRNA during
      hippocampal and cortical development.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated pentameric cation
      channels of alpha and beta subunits. The alpha5 subunit, when added to
      heteromeric complexes, alters pharmacological and physiological properties of
      nAChRs, which may be important during development. Here we have evaluated the pre
      and postnatal expression of alpha5 subunit mRNA in rat cortex and hippocampus
      using highly sensitive in situ hybridization. In the cortex, alpha5 mRNA was
      detected in the subplate, claustrum, and endopiriform nucleus at embryonic day 18
      (E18), areas with sustained expression into adulthood. Transient cortical
      expression was detected in numerous cells, scattered mainly in layers V and
      II/III, during the first 2 postnatal weeks. In the hippocampus, alpha5
      transcripts first appeared in the CA1 region at E18. During postnatal
      development, increased hybridization signal was detected in CA1 and CA3 pyramidal
      neurons and granule cells of the dentate gyrus, which strongly contrasted with
      the low levels in the adult. Interneurons in CA1/CA3 stratum radiatum and
      moleculare, and in the hilus region of the dentate gyrus, strongly expressed
      alpha5 mRNA in postnatal and adult animals. With double in situ hybridization, co
      expression of alpha5 and alpha7 mRNAs was detected in a subpopulation of
      hippocampal interneurons. In contrast, in the subiculum, numerous cells exhibited
      strong hybridization signal for alpha5 and alpha7 mRNAs, but co-expression was
      rarely detected. In conclusion, similar to other nAChR subunits, there is
      transient expression of alpha5 mRNA during cortical and hippocampal development.
      This expression pattern places nicotinic receptors containing the alpha5 subunit
      in a position to regulate glutamatergic and GABAergic transmission during the
      postnatal period.

PMID- 15558718
TI  - Synaptic distribution of the endocytic accessory proteins AP180 and CALM.
AB  - Clathrin-coated vesicles mediate a variety of endocytosis pathways in cells,
      including endocytic events at synapses. AP180 and clathrin assembly lymphoid
      myeloid leukemia protein (CALM) are clathrin accessory proteins that promote the
      formation of clathrin-coated vesicles. Both proteins bind to membrane lipids
      through their epsin N-terminal homology domains and interact with clathrin and
      related protein components through their carboxyl-terminal peptide motifs. We
      examine their neuronal expression and synaptic distribution. We show that both
      proteins are detected in synapses but demonstrate different distribution
      patterns. AP180 is located predominantly in presynaptic profiles, whereas CALM is
      found nonselectively in pre- and postsynaptic profiles and also in perisynaptic
      processes. These observations reveal an unexpected relationship between AP180 and
      the presumed non-neuronal homologue CALM. We propose that both AP180 and CALM
      function as endocytic accessory proteins at synapses, but each may regulate
      distinct clathrin pathways.

PMID- 15558719
TI  - Differential sorting and packaging of capa-gene related products in an insect.
AB  - A unique costorage of neuropeptides was recently found in the abdominal
      perisympathetic organs (PSOs) of the American cockroach, Periplaneta americana.
      Having specific antisera directed against all peptides belonging to this
      neurosecretory system, we examined the sorting of PSO-peptides in the soma of the
      median neurosecretory cells of abdominal ganglia by using immunoelectron
      microscopic double stainings. The data indicate that all six abundant
      neuropeptides of this neurohormonal system, which includes three capa-gene
      related products, are primarily incorporated into separate vesicles. These
      vesicles fuse with each other in the cytoplasm and become translucent on their
      way to the axon hillock. By means of light microscopy and MALDI-TOF mass
      spectrometry, an identical population of neuropeptides was found in interneurons
      of the brain. As revealed by subsequent immunoelectron microscopic analysis, the
      peptides of these cells are separately packed into dense core vesicles but do not
      fuse with each other. Thus, hitherto unknown cell-type-specific sorting
      mechanisms occur in neurosecretory cells and interneurons, respectively.

PMID- 15558720
TI  - Integration and segregation of inputs to higher-order neuropils of the crayfish
      brain.
AB  - Information about the input and output pathways of higher-order brain neuropils
      is essential for gaining an understanding of their functions. The present study
      examines the connectivity of two higher-order neuropils in the central olfactory
      pathway of the crayfish: the accessory lobe and its target neuropil, the
      hemiellipsoid body. It is known that the two subregions of the accessory lobe,
      the cortex and medulla, receive different inputs; the medulla receives visual and
      tactile inputs, whereas the cortex receives neither (Sandeman et al. [1995] J
      Comp Neurol 352:263-279). By using dye injections into the olfactory lobe, we
      demonstrate that the accessory lobe cortex and medulla also have differing
      connections with the olfactory lobe. These injections show that local
      interneurons joining the olfactory and accessory lobes branch primarily within
      the cortex with only limited branching within the medulla. Injections of
      different dyes into the two subregions of the hemiellipsoid body, HBI and HBII,
      show that the accessory lobe cortex and medulla also have separate output
      pathways. HBI is innervated by the output pathway from the cortex while HBII is
      innervated by the output pathway from the medulla. These injections also show
      that HBI and HBII are innervated by separate populations of local interneurons
      with differing connections to higher-order neuropils in the olfactory and visual
      pathways. These results suggest a segregation of olfactory and multimodal
      (including olfactory) inputs within both the accessory lobe and the hemiellipsoid
      body and provide evidence of important functional subdivisions within both
      neuropils.

PMID- 15558721
TI  - Single-axon tracing and three-dimensional reconstruction of centre median
      parafascicular thalamic neurons in primates.
AB  - The axonal projections from the centre median (CM)/parafascicular (Pf) thalamic
      complex in squirrel monkeys were studied after microiontophoretic injections of
      biotinylated dextran amine under electrophysiological guidance. A total of 29
      axons connected to their parent cell body were entirely reconstructed from serial
      sections with a camera lucida. Our investigation shows that the CM and Pf nuclei
      in primates comprise three types of projection neurons: (1) neurons that
      innervate densely and focally the striatum; (2) neurons that arborize diffusely
      in the cerebral cortex; and (3) neurons that innervate both striatum and cerebral
      cortex. Striatal innervation of CM origin consists of dense clusters of axon
      terminals exhibiting pedunculated varicosities and forming oblique bands in the
      dorsolateral sector of putamen (sensorimotor striatal territory). The same type
      of striatal innervation occurs in the head of caudate nucleus (associative
      striatal territory) in cases of Pf-labeled neurons. The CM neurons that target
      cerebral cortex arborize principally in motor and premotor areas, whereas Pf
      neurons innervate chiefly prefrontal areas. Cortical innervation from both nuclei
      is much more profuse in layers V and VI than in layer I. Our three-dimensional
      reconstruction studies show that dendritic and axonal arborizations of CM neurons
      extend essentially along the sagittal plane. These results revealed that, in
      contrast to rodents where virtually all Pf neurons project to both striatum and
      cortex, the primate CM/Pf complex harbors several types of highly patterned
      projection neurons. As such, this complex might be considered as an integral part
      of the widely distributed basal ganglia neuronal system.

PMID- 15558722
TI  - Insights from genomic microarrays into structural chromosome rearrangements.
AB  - Array-based comparative genomic hybridization allows high-resolution screening of
      copy number abnormalities in the genome, and becomes an increasingly important
      tool to detect deletions and duplications in tumor and post-natal cytogenetics.
      Here we illustrate that genomic arrays can also provide novel clues regarding the
      structural basis of chromosome rearrangement, including instability and
      mechanisms of formation of ring chromosomes. We also showed that array results
      might impact the recurrence risks for relatives of affected individuals. Our data
      indicate that chromosome rearrangements frequently involve more breaks than
      current cytogenetic models assume.

PMID- 15558723
TI  - A novel syndrome resembling Desbuquois dysplasia.
AB  - We report on three Tunisian siblings with a rare assortment of clinical and
      radiographic abnormalities closely resembling Desbuquois dysplasia. However, the
      siblings have had normal facies, normal hands, and were mentally normal. There
      were severe musculo-skeletal distinguishing features such as joint stiffness,
      severe kyphoscoliosis, and multiple large joint dislocations. Moreover, the
      patients had an additional remarkable radiographic feature not reported in
      Desbequois dysplasia-multiple carpal ossification centers. The diagnosis of
      Desbuquois dysplasia is more difficult in older children and adults as the
      characteristic facial features of early childhood may recede, and the metaphyseal
      growth plates obliterate. This condition of these patients represents a novel
      Desbuquois-like syndrome.

PMID- 15558724
TI  - Changing profile of couples seeking genetic counseling for consanguinity in
      Australia.
AB  - Consanguineous marriage is rare in most Western countries and, for example, in
      the USA it may be subject to regulation by both civil legislation and religious
      prescription. This is not the case in many regions of Asia and Africa where
      marriage within the family is strongly favored. Since the 1970s there has been
      widespread migration to North America, Western Europe, and Australasia from
      communities which encourage consanguineous marriage. To assess the effect of this
      trend on a genetic counseling program, the records of 302 couples referred to
      Genetic Services of Western Australia for consanguinity counseling were
      abstracted for the period 1975-2001. Overall, a family history of genetic disease
      or a previously affected child was reported in 28.8% of cases. Premarital or
      prepregnancy counseling on grounds of consanguinity was sought by 41.0% of
      couples, and a further 18.2% of consanguineous couples had been referred because
      of a consanguineous pregnancy. In 7.6% of cases a relationship closer than first
      cousin was involved. Through time there was a significant increase in the numbers
      of consanguineous consultants, and their patterns of religious affiliation and
      ethnic origin widened markedly. Although effectively excluded from entry to
      Australia prior to 1975, couples of Asian origin accounted for 25.5% of all
      consanguineous consultants. With ongoing migration, changes in the ethnic
      profiles and the specific counseling requirements of consanguineous couples can
      be expected to continue and probably accelerate.

PMID- 15558725
TI  - Tinkering and tailoring with HCV therapy: can we get away with less?

PMID- 15558726
TI  - Structural accelerated failure time models for the effects of observed exposures
      on repeated events in a clinical trial.
AB  - Structural accelerated failure time models form a unique tool for the analysis of
      causal effects of observed exposures in randomized trials. When actual exposure
      levels are not completely controlled they may be selective, i.e. depend on
      unmeasured prognostic factors. Nevertheless, consistent randomization-based
      estimators have been derived for the effect of such exposures on a right-censored
      survival outcome. In this paper, we extend the methodology to allow for
      estimation of the structural effect of an experimental vaginal gel on repeated
      occurrences of genital lesions. The marginal distribution of each ordered event
      is modelled assuming a common treatment effect. Estimation is possible by
      inverting alpha-level tests using a robust variance estimator to allow for
      correlated repeated events. We discuss the logical constraints imposed by this
      model choice as well as new challenges posed on recensoring.

PMID- 15558730
TI  - Avian superior olivary nucleus provides divergent inhibitory input to parallel
      auditory pathways.
AB  - The avian auditory brainstem displays parallel processing, a fundamental feature
      of vertebrate sensory systems. Nuclei specialized for temporal processing are
      largely separate from those processing other aspects of sound. One possible
      exception to this parallel organization is the inhibitory input provided by the
      superior olivary nucleus (SON) to nucleus angularis (NA), nucleus magnocellularis
      (NM), and nucleus laminaris (NL) and contralateral SON (SONc). We sought to
      determine whether single SON neurons project to multiple targets or separate
      neuronal populations project independently to individual target nuclei. We
      introduced two different fluorescent tracer molecules into pairs of target nuclei
      and quantified the extent to which retrogradely labeled SON neurons were double
      labeled. A large proportion of double-labeled SON somata were observed in all
      cases in which injections were made into any pair of ipsilateral targets (NA and
      NM, NA and NL, or NM and NL), suggesting that many individual SON neurons project
      to multiple targets. In contrast, when injections involved the SONc and any or
      all of the ipsilateral targets, double labeling was rare, suggesting that
      contralateral and ipsilateral targets are innervated by distinct populations of
      SON neurons arising largely from regionally segregated areas of SON. Therefore,
      at the earliest stages of auditory processing, there is interaction between
      pathways specialized to process temporal cues and those that process other
      acoustic features. We present a conceptual model that incorporates these results
      and suggest that SON circuitry, in part, functions to offset interaural intensity
      differences in interaural time difference processing.

PMID- 15558731
TI  - Membrane-associated guanylate kinase proteins MPP4 and MPP5 associate with Veli3
      at distinct intercellular junctions of the neurosensory retina.
AB  - MPP4 and MPP5 are closely related members of the p55-subfamily of membrane
      associated guanylate kinases (MAGUKs) known to mediate the assembly of protein
      complexes at the plasma membrane of cell-cell junctions. Both MPP4 and MPP5 have
      been implicated in retinal function; however, their specific roles in the
      cellular mechanisms underlying vision are largely unknown. Here, we generated
      specific poly- and monoclonal antibodies against the two proteins and show that
      MPP4 and MPP5 are localized at distinct sites of cell-cell contact in the mouse
      retina. While MPP4 is a component of the synaptic terminals of photoreceptors,
      MPP5 exclusively localizes to apical membrane domains of the outer limiting
      membrane (OLM) junctions. The vertebrate homologs of Caenorhabditis elegans lin
      7, Veli1, -2, and -3, have previously been identified as putative binding
      partners of MPP5. In this study, we show that MPP4 directly interacts with the
      Veli proteins via L27 heterodimerization in vitro. In addition, two of the three
      Veli isoforms, Veli1 and -3, are demonstrated to be expressed in the mouse
      retina. Immunofluorescence microscopy reveals extensive colocalization of Veli3
      with both MPP4 and MPP5. This association of Veli3 with either MPP4 or MPP5
      suggests that the MAGUKs recruit Veli3 and its binding partners to different
      cellular regions of the retina where they may participate in the organization of
      specialized intercellular junctions.

PMID- 15558732
TI  - Embryonic and postnatal development of GABA, calbindin, calretinin, and
      parvalbumin in the mouse claustral complex.
AB  - We analyzed the development of immunoreactive expression patterns for the
      neurotransmitter gamma-aminobutyric acid (GABA) and the calcium-binding proteins
      calbindin, calretinin, and parvalbumin in the embryonic and postnatal mouse
      claustral complex. Each calcium-binding protein shows a different temporal and
      spatial pattern of development. Calbindin-positive cells start to be seen very
      early during embryogenesis and increase dramatically until birth, thus becoming
      the most abundant cell type during embryonic development, especially in the
      ventral pallial part of the claustrum. The distribution of calbindin neurons
      throughout the claustrum during embryonic development partly parallels that of
      GABA neurons, suggesting that at least part of the calbindin neurons of the
      claustral complex are GABAergic and originate in the subpallium. Parvalbumin
      cells, on the other hand, start to be seen only postnatally, and their number
      then increases while the density of calbindin neurons decreases. Based on
      calretinin expression in axons, the core/shell compartments of the dorsal
      claustrum start to be clearly seen at embryonic day 18.5 and may be related to
      the development of the thalamoclaustral input. Comparison with the expression of
      Cadherin 8, a marker of the developing dorsolateral claustrum, indicates that the
      core includes a central part of the dorsolateral claustrum, whereas the shell
      includes a peripheral area of the dorsolateral claustrum, plus the adjacent
      ventromedial claustrum. The present data on the spatiotemporal developmental
      patterns of several subtypes of GABAergic neurons in the claustral complex may
      help for future studies on temporal lobe epilepsies, which have been related to
      an alteration of the GABAergic activity.

PMID- 15558733
TI  - Neurogenesis within the juvenile zebra finch telencephalic ventricular zone: a
      map of proliferative activity.
AB  - Localized regions of increased cellular proliferation within the ventricular zone
      (VZ) of juvenile male songbirds may contain progenitor cells that give rise to
      song-control neurons and, thereby, contribute to the construction of brain areas
      important for song learning. The purpose of this study was to examine levels of
      cell division throughout the telencephalic VZ of juvenile birds. A single pulse
      of [(3)H]thymidine was administered to 30-day male and female zebra finches, and
      the birds were killed 2 hours later. The VZ was divided into segments throughout
      the entire anterior-posterior and dorsal-ventral neuraxes, and levels of
      thymidine labeling were measured within each subdivision. By subdividing the VZ
      into segments, we were able to construct a "map" of proliferation throughout the
      telencephalic VZ, thereby allowing us to compare levels of mitotic activity
      within corresponding locations of the VZ between males and females. Our map
      revealed two major findings: (1) proliferation in both juvenile males and females
      was spatially differentiated throughout the VZ, suggesting that mitotic activity
      is differentially regulated across the neuraxis; (2) sex differences in
      proliferation were present in 30-day-old birds, but were highly restricted. The
      most robust sexual dimorphism occurred within the ventral aspect of the VZ at
      rostral levels of the song-control nucleus Area X, with males demonstrating an
      increased number of dividing cells compared with females. This result raises the
      possibility that Area X neurons in males are derived from committed progenitors
      within the adjacent VZ in close proximity to this nucleus.

PMID- 15558734
TI  - Octavolateral projections and organization in the medulla of a teleost fish, the
      sleeper goby (Dormitator latifrons).
AB  - This study is the first to employ simultaneous labeling with different colored
      fluorescent dyes and confocal microscopy to investigate the central projections
      of the octavolateral nerves in any fish. Three-dimensional reconstructions of the
      hindbrain octavolateral nuclei were made and overlap of octavolateral projections
      was assessed in a teleost, the sleeper goby (Dormitator latifrons). The
      octavolateral nerves, which innervate the otolithic organs, semicircular canals,
      and lateral lines, project to seven hindbrain nuclei in diverse, complex
      patterns. The medulla is generally organized with auditory regions dorsal to
      vestibular regions. The intermediate subdivision of the descending octaval
      nucleus (DON) receives interdigitating projections from the otolithic organs, and
      the dorsomedial DON likely integrates multiple auditory inputs. Afferents from
      the three otolithic organs (the utricle, saccule, and lagena) project to the
      intermediate DON in approximately equal proportion, supporting physiological
      evidence that suggests auditory roles for all three otolithic organs in the
      sleeper goby. The anterior octaval nucleus receives partially segregated inputs
      from the octavolateral organs. The dorsal division of the magnocellular octaval
      nucleus (MgON) receives highly overlapping otolithic organ and semicircular canal
      input, and we propose that this region is a major octaval integration center.
      Regions in the ventral medulla (the tangential octaval nucleus, ventral DON, and
      ventral MgON) receive mainly utricular and semicircular canal inputs, suggesting
      vestibular roles. Each semicircular canal nerve projects to distinct regions of
      the hindbrain, with little overlap in most octaval nuclei. Efferent neurons
      receive bilateral input and project unilaterally to the octavolateral organs.

PMID- 15558736
TI  - Who owns the data?

PMID- 15558739
TI  - Sidechain biology and the immunogenicity of PDC-E2, the major autoantigen of
      primary biliary cirrhosis.
AB  - The E2 component of mitochondrial pyruvate dehydrogenase complex (PDC-E2) is the
      immunodominant autoantigen of primary biliary cirrhosis. Whereas lipoylation of
      PDC-E2 is essential for enzymatic activity and predominates under normal
      conditions, other biochemical systems exist that also target the lysine residue,
      including acylation of fatty acids or xenobiotics and ubiquitinylation. More
      importantly, the immunogenicity can be affected by derivatization of the lysine
      residue, as the recognition of lipoylated PDC-E2 by patient autoantibodies is
      enhanced compared with octanoylated PDC-E2. Furthermore, our laboratory has shown
      that various xenobiotic modifications of a peptide representing the
      immunodominant region of PDC-E2 are immunoreactive against patient sera. The only
      purported regulatory system that prevents the accumulation of potentially
      autoreactive PDC-E2 is glutathionylation, in which the lysine-lipoic acid moiety
      is further modified with glutathione during apoptosis. Interestingly, this system
      is found in several cell lines, including HeLa, Jurkat, and Caco-2 cells, but not
      in cholangiocytes and salivary gland epithelial cells, both of which are targets
      for destruction in primary biliary cirrhosis. Hence, the failure of this or other
      regulatory system(s) may overwhelm the immune system with immunogenic PDC-E2 that
      can initiate the breakdown of tolerance in a genetically susceptible individual.
      In this review the authors survey the data available on the biochemical life of
      PDC-E2, with particular emphasis on the lysine residue and its known interactions
      with machinery involved in various posttranslational modifications.

PMID- 15558745
TI  - Issues in high-throughput comparative modelling: a case study using the ubiquitin
      E2 conjugating enzymes.
AB  - Sequences of the ubiquitin-conjugating enzyme (UBC or E2) family were used as a
      test set to investigate issues associated with the high-throughput comparative
      modelling of protein structures. A semi-automatic method was initially developed
      with particular emphasis on producing models of a quality suitable for structural
      comparison. Structural and sequence features of the E2 family were used to
      improve the sequence alignment and the quality of the structural templates.
      Initially, failure to correct for subtle structural inconsistencies between
      templates lead to problems in the comparative analysis of the UBC electrostatic
      potentials. Modelling of known UBC structures using Modeller 4.0 showed that
      multiple templates produced, on average, no better models than the use of just
      one template, as judged by the root-mean-squared deviation between the
      comparative model and crystal structure backbones. Using four different quality
      checking methods, for a given target sequence, it was not possible to distinguish
      the model most similar to the experimental structure. The UBC models were thus
      finally modelled using only the crystal structure template with the highest
      sequence identity to the target to be modelled, and producing only one model
      solution. Quality checking was used to reject models with obvious structural
      anomalies (e.g., bad side-chain packing). The resulting models have been used for
      a comparison of UBC structural features and of their electrostatic potentials.
      The work was extended through the development of a fully automated pipeline that
      identifies E2 sequences in the sequence databases, aligns and models them, and
      calculates the associated electrostatic potential.

PMID- 15558746
TI  - PhosphaBase: an ontology-driven database resource for protein phosphatases.
AB  - PhosphaBase is an ontology-driven database resource containing information on the
      protein phosphatase family. It is the first public resource dedicated to protein
      phosphatases, which are enzymes that perform dephosphorylation reactions. In
      conjunction with the phosphorylation action of protein kinases, phosphatases are
      involved in important control and communication mechanisms in the cell. They have
      also been implicated in many human diseases, including diabetes and obesity,
      cancers, and neurodegenerative conditions. PhosphaBase aims to centralize the
      growing base of knowledge in the phosphatase research domain. The resource is
      built around a formal, domain-specific DAML+OIL ontology, and the data are
      collected from heterogeneous biological sources using Gene Ontology terms as a
      means of data extraction. The overall ontology-driven architecture provides a
      robust structure with distinct advantages for sustainability and provides the
      potential for the development of diagnostic tools, as well as a data repository.

PMID- 15558747
TI  - Nerve growth factor and acetyl-L-carnitine evoked shifts in acetyl-CoA and
      cholinergic SN56 cell vulnerability to neurotoxic inputs.
AB  - Different groups of brain cholinergic neurons display variable susceptibility to
      similar neurotoxic inputs. The aim of this work was to find out whether changes
      in cholinergic phenotype may alter the availability of acetyl-CoA in
      mitochondrial compartment and thereby the viability of cholinergic neurons.
      Cyclic AMP (cAMP) and retinoic acid caused differentiation (DC) of T17 TrkA(+)
      cholinergic neuroblastoma cells. In addition, it increased the choline
      acetyltransferase (ChAT) activity, Ca(2+) accumulation and cytoplasmic acetyl-CoA
      level, but decreased mitochondrial acetyl-CoA and cell resistance to amyloid
      beta(25-35) (Abeta) toxicity. Nerve growth factor (NGF) caused similar
      alterations in the nondifferentiated cells (NC). On the other hand, in DC NGF
      suppressed ChAT activity and elevated mitochondrial level of acetyl-CoA but also
      caused a further increase of Ca(2+) content and cell susceptibility to Abeta. The
      significant inverse correlation was found between ChAT activity and mitochondrial
      levels of acetyl-CoA. Abeta markedly reduced the expression of cholinergic
      phenotype, acetyl-CoA content, and viability of DC. These effects were absent or
      much less pronounced in NC. Acetyl-L-carnitine reversed suppressing effects of
      Abeta on acetyl-CoA levels and ChAT activity but did not reverse increased
      mortality in DC. Presented data indicate that increased transmitter activity in
      highly differentiated cholinergic neurons, decreased acetyl-CoA level in their
      mitochondrial compartment, and increased Ca(2+) accumulation can make them more
      prone to neurotoxic conditions. Phenotype-dependent changes in intracellular
      distribution of acetyl-CoA thus play an important role in regulation of viability
      and transmitter function in brain cholinergic neurons.

PMID- 15558748
TI  - Ex vivo NMR study of lactate metabolism in rat brain under various depressed
      states.
AB  - Brain endogenous lactate metabolism was investigated by ex vivo nuclear magnetic
      resonance (NMR) spectroscopy study after the infusion of rats with a solution of
      glucose and lactate labeled as either [3-(13)C]lactate or [1-(13)C]glucose, when
      their cerebral activity was more or less depressed under the influence of either
      pentobarbital, alphachloralose, or morphine. We found that: (1) the ratio between
      the enrichment of alanine C3 and that of glutamate C4, gamma-aminobutyric acid
      (GABA) C2, glutamine C4, or aspartate C3 decreased from pentobarbital to
      alphachloralose and morphine whatever the labeled precursor, indicating a link
      between metabolic and cerebral activity; (2) under glucose + [3-(13)C]lactate
      infusion, alanine C3 and acetyl-CoA C2 enrichments were higher than that of
      lactate C3, revealing the occurrence of an isotopic dilution of the brain
      exogenous lactate (arising from the blood) by lactate from the brain (endogenous
      lactate), and that the latter was synthesized from glycolysis in a compartment
      other than neurons; and (3) the contribution of labeled glucose and lactate to
      acetyl-CoA and amino acid enrichment indicated that the involvement of blood
      glucose relative to that of blood lactate to brain metabolism was correlated with
      cerebral activity. The evolution of metabolite enrichments, however, indicated
      that the cerebral activity-dependent increase in the contribution of blood
      glucose relative to that of blood lactate to brain metabolism occurred partly via
      the increase in lactate metabolism generated from astrocytic glycolysis. These
      findings support the hypothesis for an astrocyte-neuron lactate shuttle component
      in the coupling mechanism between cerebral activity and energy metabolism.

PMID- 15558749
TI  - The genetics of tethered cord syndrome.

PMID- 15558750
TI  - Selective regulation of 14-3-3eta in primary culture of cerebral cortical neurons
      and astrocytes during development.
AB  - The 14-3-3 proteins exist predominantly in the brain and may play regulatory
      roles in cellular processes of growth, differentiation, survival, and apoptosis.
      The biological functions, however, of the various 14-3-3 isoforms (beta, epsilon,
      eta, gamma, and zeta) in the brain remain unclear. We have reported previously
      upregulation of 14-3-3gamma in ischemic astrocytes. In the present study, we
      report selective regulation of 14-3-3eta in cultured cerebral cortical neurons
      and astrocytes during in vitro development. In cultured neurons, gene expression
      levels of 14-3-3eta increase with culture age (0-10 days). Brain-derived
      neurotrophic factor and neurotrophin-3 upregulate 14-3-3eta gene expression. In
      cultured astrocytes, 14-3-3eta is downregulated with culture age (1-5 weeks). The
      gene expression level of 14-3-3eta is not affected by scratch injury in
      astrocytes or by ischemia in neurons. These data suggest a possible role of 14-3
      3eta in growth and differentiation of neurons and astrocytes, indicating an
      intricate mechanism governing coordinated and well-controlled developmental
      events in the brain to ensure normal neural functions.

PMID- 15558751
TI  - Evaluation of brain mitochondrial glutamate and alpha-ketoglutarate transport
      under physiologic conditions.
AB  - Some models of brain energy metabolism used to interpret in vivo (13)C nuclear
      magnetic resonance spectroscopic data assume that intramitochondrial alpha
      ketoglutarate is in rapid isotopic equilibrium with total brain glutamate, most
      of which is cytosolic. If so, the kinetics of changes in (13)C-glutamate can be
      used to predict citric acid cycle flux. For this to be a valid assumption, the
      brain mitochondrial transporters of glutamate and alpha-ketoglutarate must
      operate under physiologic conditions at rates much faster than that of the citric
      acid cycle. To test the assumption, we incubated brain mitochondria under
      physiologic conditions, metabolizing both pyruvate and glutamate and measured
      rates of glutamate, aspartate, and alpha-ketoglutarate transport. Under the
      conditions employed (66% of maximal O(2) consumption), the rate of synthesis of
      intramitochondrial alpha-ketoglutarate was 142 nmol/min.mg and the combined
      initial rate of alpha-ketoglutarate plus glutamate efflux from the mitochondria
      was 95 nmol/min.mg. It thus seems that much of the alpha-ketoglutarate
      synthesized within the mitochondria proceeds around the citric acid cycle without
      equilibrating with cytosolic glutamate. Unless the two pools are in such rapid
      exchange that they maintain the same percent (13)C enrichment at all points,
      (13)C enrichment of glutamate alone cannot be used to determine tricarboxylic
      acid cycle flux. The alpha-ketoglutarate pool is far smaller than the glutamate
      pool and will therefore approach steady state faster than will glutamate at the
      metabolite transport rates measured.

PMID- 15558752
TI  - Nitric oxide from inflammatory-activated glia synergizes with hypoxia to induce
      neuronal death.
AB  - Inflammatory-activated glia are seen in numerous central nervous system (CNS)
      pathologies and can kill nearby neurons through the release of cytotoxic
      mediators. Glia, when activated, can express the inducible isoform of nitric
      oxide synthase (iNOS) producing high levels of nitric oxide (NO), which can kill
      neurons in certain conditions. We show, however, that inflammatory activation of
      glia in a mature culture of cerebellar granule neurons and glia causes little or
      no neuronal death under normal (21%) oxygen conditions. Similarly, hypoxia (2%
      oxygen) or low levels of an NO donor (100 microM DETA/NO) caused little or no
      neuronal death in nonactivated cultures. If inflammatory activation of glia or
      addition of NO donor was combined with hypoxia, however, extensive neuronal death
      occurred. Death in both cases was prevented by the N-methyl-D-aspartate (NMDA)
      receptor blocker MK-801, implying that death was mediated by the glutamate
      receptor. Low levels of NO were found to increase the apparent K(M) of cellular
      oxygen consumption for oxygen, probably due to NO-induced inhibition of
      mitochondrial respiration, in competition with oxygen, at cytochrome oxidase.
      Necrotic death, induced by hypoxia plus DETA/NO, was increased further by
      deoxyglucose, an inhibitor of glycolysis, suggesting that necrosis was mediated
      by energy depletion. Hypoxia was found to be a potent stimulator of microglia
      proliferation, but this proliferation was not significant in inflammatory
      activated cultures. These results suggest that low levels of NO can induce
      neuronal death under hypoxic conditions, mediated by glutamate after NO
      inhibition of respiration in competition with oxygen. Brain inflammation can thus
      sensitize to hypoxia-induced death, which may be important in pathologies such as
      stroke, neurodegeneration, and brain aging.

PMID- 15558753
TI  - COL11A2 mutation associated with autosomal recessive Weissenbacher-Zweymuller
      syndrome: molecular and clinical overlap with otospondylomegaepiphyseal dysplasia
      (OSMED).
AB  - Autosomal recessive Weissenbacher-Zweymuller syndrome (WZS) is a skeletal
      dysplasia characterized by rhizomelic dwarfism and severe hearing loss. Mutations
      in the COL11A2 gene have been implicated in causing the autosomal dominant form
      of this syndrome as well as non-ocular Stickler syndrome and the autosomal
      recessive syndrome otospondylomegaepiphyseal dysplasia (OSMED). In a
      consanguineous Bedouin tribe living in Southern Israel, five individuals affected
      by autosomal recessive WZS were available for genetic analysis. Homozygosity of a
      mutation in the COL11A2 gene was found in all affected individuals. This finding
      lends molecular support to the clinical notion that autosomal recessive WZS and
      OSMED are a single entity.

PMID- 15558754
TI  - Prosthetic mitral valvuloplasty.
AB  - A 78-year-old man underwent mitral valve replacement with a no. 33 Hancock
      porcine bioprosthesis for severe mitral regurgitation. Postoperatively, a
      transthoracic echocardiogram (TTE) revealed a mean mitral valve gradient (MVG) of
      4 mm Hg, a calculated mitral valve area (MVA) of 2.8 cm(2), and no mitral
      regurgitation. Eighteen months later, he presented to the emergency room with
      progressive dyspnea. Repeat TTE demonstrated severe mitral stenosis (MVG, 16 mm
      Hg; MVA, 0.9 cm(2)). The patient was deemed high risk for a repeat valve
      replacement, and percutaneous valvuloplasty was performed with an Inoue balloon
      catheter inflated to 26 mm. The patient's symptoms dramatically improved, as did
      his hemodynamics (MVG, 5 mm Hg; MVA, 1.6 cm(2)). There was no evidence of mitral
      regurgitation and the successful results were maintained after 10 months of
      follow-up. Since its introduction in 1987, there have been only nine cases
      reporting successful balloon valvulotomy in prosthetic mitral valves. While
      percutaneous valvulotomy is the intervention of choice for native mitral
      stenosis, it is rarely performed in prosthetic valves, with surgical valve
      replacement being the treatment of choice. Our case was successful and may
      suggest a niche to reconsider using the procedure in certain clinical
      circumstances.

PMID- 15558755
TI  - Erosion of Amplatzer septal occluder device after closure of secundum atrial
      septal defects: review of registry of complications and recommendations to
      minimize future risk.
AB  - The objectives of this study were to identify possible risk factors that may lead
      to erosion of the Amplatzer septal occluder (ASO) and recommend ways to minimize
      future risk. There have been rare occurrences of adverse events with development
      of pericardial effusion after ASO placement. Identification of high-risk cases,
      early recognition, and prompt intervention may minimize the future risks of
      adverse events. In all patients who developed hemodynamic compromise after ASO
      placement, echocardiograms (pre-, intra-, and postprocedure), atrial septal
      defect (ASD) size (nonstretched, stretched), size of the device used,
      cineangiograms, and operative records were reviewed by a panel selected by AGA
      Medical Corporation. The findings were compared to the premarket approval data
      obtained from FDA-approved clinical trials that were conducted in the United
      States, before the device was approved. A total of 28 cases (14 in United States)
      of adverse events were reported to AGA Medical. All erosions occurred at the dome
      of the atria, near the aortic root. Deficient aortic rim was seen in 89% and the
      defect described as high ASD, suggesting deficient superior rim. The device to
      unstretched ASD ratio was significantly larger in the adverse event group when
      compared to the FDA trial group. The incidence of device erosion in the United
      States was 0.1%. The risk of device erosion with ASO is low and complications can
      be decreased by identifying high-risk patients and following them closely.
      Patients with deficient aortic rim and/or superior rim may be at higher risk for
      device erosion. Oversized ASO may increase the risk of erosion. The defect should
      not be overstretched during balloon sizing. Patients with small pericardial
      effusion at 24 hr should have closer follow-up.

PMID- 15558756
TI  - Balloon crush: treatment of bifurcation lesions using the crush stenting
      technique as adapted for transradial approach of percutaneous coronary
      intervention.
AB  - The recent advent of drug-eluting stents has allowed the crush stenting technique
      to be adopted, thus simplifying the treatment of bifurcation coronary artery
      lesions. However, this can only be achieved in 7 Fr or greater guiding catheters,
      hence precluding most transradial percutaneous coronary interventions that are
      usually undertaken using 6 Fr or less guiding catheters. We assessed the
      feasibility of balloon stent crush as a stepwise procedure in achieving
      bifurcation crush stenting in 6 Fr transradial percutaneous coronary
      interventions. Since it is not possible to place two stents through a 6 Fr
      guiding catheter, we have adapted the crush stenting technique by initially
      placing a stent in the side branch and a balloon in the main vessel. The side
      branch stent is then deployed against the main vessel balloon that is later
      inflated, crushing the side branch stent within the main vessel. The main vessel
      is then stented and the side branch recrossed for kissing inflations. Seven
      patients (five males; age range, 47-78 years) with bifurcation lesions were
      treated using the above-described technique without major complications. Balloon
      crush of the side branch stent were successfully achieved in all cases without
      balloon trapping. In six cases where side branch recrossing was attempted, all
      were successful and kissing balloon inflations were undertaken in five cases. We
      have demonstrated that the modified crush stenting technique is feasible and can
      be safely adapted for use in a 6 Fr transradial percutaneous coronary
      intervention approach.

PMID- 15558757
TI  - Long-term clinical and angiographic outcome of patients with occlusive in-stent
      restenosis treated with (32P) beta-brachytherapy.
AB  - The objective of this study was to determine the safety and efficacy of (32)P
      beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with
      occlusive ISR were generally excluded from the randomized clinical trials on
      intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have
      shown reductions in restenosis rate and need for revascularization procedures. We
      analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27
      patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with
      nonocclusive high-risk ISR. The primary outcome measure was frequency of in
      lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates
      of major adverse cardiac events (MACE), target vessel revascularization (TVR),
      clinically driven TVR, and target lesion revascularization (TLR). (32)P beta
      brachytherapy was feasible and safe and provided similar postprocedural
      angiographic results in the two clinically comparable groups. However, the 7
      month binary restenosis rate was higher in the occlusive group, as were the MACE
      and late total occlusion rates. Multivariate logistic analysis of the overall
      population indicated occlusive pattern to be the only independent predictor of
      angiographic restenosis. In both groups, recurrent lesions most often showed a
      focal pattern with significant reduction of length. Although safe and effective
      in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient
      to avoid long-term restenosis in patients with occlusive lesions. Further studies
      should determine the most suitable source and dosage of brachytherapy for
      patients with occlusive ISR.

PMID- 15558758
TI  - SCAI statement on ad hoc versus the separate performance of diagnostic cardiac
      catheterization and coronary intervention.
AB  - Coronary intervention may be combined with diagnostic cardiac catheterization or
      performed separately. In the early years of angioplasty, performing these
      procedures separately was standard practice. Gradually, ad hoc intervention
      (performing diagnostic angiography and coronary intervention within the same
      session) has become more common, largely because of its convenience for patients
      and efficiency for physicians. However, the safety and potential cost savings of
      this approach remain uncertain. Criteria for the appropriate use of ad hoc
      intervention have not been established. Ad hoc intervention is reasonable for
      many, but not appropriate for all patients and should not be considered standard
      therapy. This document updates an earlier review of this topic and provides
      suggestions for the use of ad hoc intervention as a routine strategy.

PMID- 15558759
TI  - Usefulness of conquest guidewire for retrieval of an entrapped rotablator burr.
AB  - We experienced an entrapped rotablator burr that could not be retrieved even by
      deep seating of the guiding catheter. We successfully retrieved the burr by
      balloon inflation after the tapered tip of a Conquest wire managed to penetrate
      the quite hard plaque and pass through the outer lumen of the burr.

PMID- 15558760
TI  - New bifurcation stenting technique: shunt stenting.
AB  - The optimal treatment of bifurcation lesions remains controversial. We describe a
      new technique we term shunt stenting. This technique incorporates both the new
      technology of drug-eluting stents and a novel procedure for optimizing the ostial
      side branch stent positioning. To date, early angiographic and clinical follow-up
      have been encouraging.

PMID- 15558761
TI  - Implantation of a second closure device in patients with residual shunt after
      percutaneous closure of patent foramen ovale.
AB  - Percutaneous closure of patent foramen ovale (PFO) in patients with presumed
      paradoxical embolism yields complete occlusion in > 90% of patients using
      contemporary closure devices. Patients with a residual shunt after percutaneous
      PFO closure have been found at increased risk for recurrent paradoxical events.
      Treatment options for such patients include medical treatment using antiplatelet
      drugs or oral anticoagulation, surgical device removal and patch closure, and
      percutaneous implantation of a second closure device. We report our experience
      with implantation of a second closure device in 10 patients with more than a
      minimal residual shunt < or = 6 months after percutaneous PFO closure. Procedure
      and fluoroscopy times were similar for the initial and repeat intervention (32
      vs. 30 min and 5 vs. 6 min, respectively; P = NS). There were no procedural
      complications during implantation of the second closure device. Follow-up
      transesophageal echocardiography 6 months after the second percutaneous
      intervention revealed complete PFO closure in nine (90%) patients. Therefore,
      implantation of a second closure device in patients with persistence of more than
      a residual shunt after percutaneous PFO closure appears safe and effective.

PMID- 15558762
TI  - Effects of chronic administered guanosine on behavioral parameters and brain
      glutamate uptake in rats.
AB  - Oral and intraperitoneal administration of the nucleoside guanosine have been
      shown to prevent quinolinic acid- (QA) and alpha-dendrotoxin-induced seizures,
      impair memory, and impair anxiety in rats and mice. We investigated the effect of
      2-weeks ad lib orally administered guanosine (0.5 mg/ml) on seizures induced by
      QA, inhibitory avoidance memory, and locomotor performance in rats. We also
      studied the mechanism of action of guanosine through the measurement of its
      concentration in the cerebrospinal fluid (CSF) and its effect on glutamate uptake
      in cortical slices of rats. QA produced seizures in 85% of rats, an effect
      partially prevented by guanosine (53% of seizures; P = 0.0208). Guanosine also
      impaired retention on the inhibitory avoidance task (P = 0.0278) and decreased
      locomotor activity on the open field test (P = 0.0101). The CSF guanosine
      concentration increased twofold in the treated group compared to that in the
      vehicle group (P = 0.0178). Additionally, QA promoted a 30% decrease in glutamate
      uptake as compared to that with intracerebroventricular saline administration, an
      effect prevented by guanosine in animals protected against QA-induced seizures.
      Altogether, these findings suggest a potential role of guanosine for treating
      diseases involving glutamatergic excitotoxicity such as epilepsy. These effects
      seem to be related to modulation of glutamate uptake.

PMID- 15558763
TI  - Homeostasis of neuroactive amino acids in cultured cerebellar and neocortical
      neurons is influenced by environmental cues.
AB  - Neuronal function is highly influenced by the extracellular environment. To study
      the effect of the milieu on neurons from cerebellum and neocortex, cells from
      these brain areas were cultured under different conditions. Two sets of cultures,
      one neocortical and one cerebellar neurons, were maintained in media containing
      [U-(13)C]glucose for 8 days at initial concentrations of 12 and 28 mM glucose,
      respectively. Other sets of cultures (8 days in vitro) maintained in a medium
      containing initially 12 mM glucose were incubated subsequently for 4 hr either by
      addition of [U-(13)C]glucose to the culture medium (final concentration 3 mM) or
      by changing to fresh medium containing [U-(13)C]glucose (3 mM) but without
      glutamine and fetal calf serum. (13)C Nuclear magnetic resonance (NMR) spectra
      revealed extensive gamma-aminobutyric acid (GABA) synthesis in both cultured
      neocortical and cerebellar neurons after maintenance in medium containing [U
      (13)C]glucose for 8 days, whereas no aspartate labeling was observed in these
      spectra. Mass spectrometry analysis, however, revealed high labeling intensity of
      aspartate, which was equal in the two types of neurons. Addition of [U
      (13)C]glucose (4 hr) on Day 8 in culture led to a similar extent of labeling of
      GABA in neocortical and in cerebellar cultures, but the cellular content of GABA
      was considerably higher in the neocortical neurons. The cellular content of
      alanine was similar regardless of culture type. Comparing the amount of labeling,
      however, cerebellar neurons exhibited a higher capacity for alanine synthesis.
      This is compatible with the fact that cerebellar neurons could ameliorate a low
      alanine content after culturing in low glucose (12 mM) by a 4-hr incubation in
      medium containing 3 mM glucose. A low glucose concentration during the culture
      period and a subsequent medium change were associated with decreases in
      glutathione and taurine contents. Moreover, glutamate and GABA contents were
      reduced in cerebellar cultures under either of these conditions. In neocortical
      neurons, the GABA content was decreased by simultaneous exposure to low glucose
      and change of medium. These conditions also led to an increase in the aspartate
      content in both types of cultures, although most pronounced in the neocortical
      neurons. Further experiments are needed to elucidate these phenomena that
      underline the impact of extracellular environment on amino acid homeostasis.

PMID- 15558764
TI  - Carotid stenting for symptomatic radiation-induced arteritis complicated by
      recurrent aneurysm formation.
AB  - We describe a 56-year-old male who underwent successful carotid stenting (CS)
      with adjuvant distal protection in response to symptomatic radiation-induced
      carotid disease. During the CS procedure, it was incidentally noted that the
      lesion yield pressure was surprisingly low (2 atm). The patient returned with
      local symptoms from common carotid aneurysmal dilation at the proximal edge of
      the stent that was successfully treated with a stent graft. A second aneurysm
      developed proximal to the stent graft and, based on intravascular ultrasound
      mapping, he ultimately underwent venous bypass covered by a free-muscle graft. We
      believe the low lesion yield pressure in this case reflected loss of vessel
      integrity and it may be prudent to avoid oversizing the stent in such patients.

PMID- 15558765
TI  - Occupational hazards of interventional cardiologists: prevalence of orthopedic
      health problems in contemporary practice.
AB  - Invasive cardiologists generally consider radiation to be the chief occupational
      hazard. Heavy leaded aprons worn to reduce this risk may be associated with
      orthopedic complications. This study was designed to characterize the prevalence
      of these occupational health problems. The Interventional Committee of the
      Society for Cardiac Angiography and Interventions (SCAI) sent to its Internet
      registered members a Web-based survey. Inquiries included age, years of invasive
      practice, and diagnostic/interventional cases/year. Questions (yes/no) focused on
      orthopedic (spine, hips, knees, and ankles) and radiation-associated problems
      (cataracts and cancers). The survey was sent to over 1,600 members with 424
      responses. Responders were on average busy and experienced, performing
      catheterization > 10 years in 62% of cases and > 20 years in 24% others. Average
      annual diagnostic-only case load was > 200/year in 72%, > 300/year in 43%, and >
      500/year in 18% of responders. Reported annual interventional caseload was >
      100/year in 83%, > 200/year in 37%, and > 300/year in 15% of operators.
      Orthopedic problems included spine problems in 42% of responders (of these, 70%
      were lumbosacral and 30% cervical). Hip, knee, or ankle problems were noted in
      28% of operators. Spine problems were related to the annual procedural caseload
      and the number of years in practice. Over one-third reported spine problems had
      caused them to miss work. The results of the radiation queries were inconclusive.
      These results document that interventional cardiologists commonly suffer
      orthopedic disease, frequently leading to lost work days.

PMID- 15558766
TI  - New method to increase a backup support of a 6 French guiding coronary catheter.
AB  - A 6 Fr guiding catheter is commonly used in the percutaneous coronary
      intervention (PCI). However, one of the limitations of the 6 Fr guiding catheter
      is its weak backup support compared to a 7 or an 8 Fr guiding catheter. In this
      article, we present a new system for PCI called the five-in-six system. Between
      March 2003 and September 2003, this system was tried on eight chronic total
      occlusion cases. The advantage of the five-in-six system is that it increases
      backup support of a 6 Fr guiding catheter.

PMID- 15558767
TI  - Relief of pseudostenosis using the transit exchange catheter.
AB  - Pseudostenosis is a generally benign complication of percutaneous coronary
      intervention that is caused by the mechanical deformation of a tortuous artery by
      the guidewire. We describe two cases of a tortuous right coronary artery in which
      pseudostenosis was relieved by placing a Transit exchange catheter (Cordis)
      distally and subsequently removing the guidewire. This technique safely confirmed
      the diagnosis of pseudostenosis without losing guidewire position or requiring
      additional wires and balloons.

PMID- 15558768
TI  - Novel simultaneous combination chemical thrombolysis/rheolytic thrombectomy
      therapy for acute critical limb ischemia: the power-pulse spray technique.
AB  - The novel power-pulse spray (P-PS) technique maximizes and combines the
      advantages and minimizes the disadvantages of both chemical thrombolysis (CT) and
      rheolytic thrombectomy (RT). Forty-nine consecutive patients with iliofemoral
      thrombotic occlusion were treated via P-PS technique. Using a 6 Fr RT catheter,
      saline prime was exchanged for thrombolytic solution [group 1, 10-20 mg
      tenecteplase (TNK)/50 cc saline, n = 25; group 2, 1,000,000 urokinase (UK)/50 cc
      saline, n = 24]. The outflow port was closed, then the catheter was advanced at 1
      mm increments while pulsing lytic agent. After 30-min lysis time, RT and
      definitive treatment of the underlying stenosis were performed. Procedure success
      was 23/25 (92%) and 22/24 (91.6%) for group 1 and 2, respectively. The mean total
      procedure time was 72 and 75 min in group 1 and 2, respectively. Thirty-day limb
      salvage was 91% in both groups. There were no major surgical complications. The P
      PS technique is safe and effective using either UK or TNK, offering several
      potential advantages over monotherapy, including more rapid revascularization,
      decreases systemic lytic exposure and bleeding complications while facilitating
      both CT and RT capacity and efficacy.

PMID- 15558769
TI  - Corrected TIMI frame count: applicability in modern digital catheter laboratories
      when different frame acquisition rates are used.
AB  - The original description of the TIMI frame count (TFC) method was based on
      angiograms acquired at 30 f/sec. Modern digital angiograms are acquired at lower
      frame rates (between 12.5 and 25 f/sec). Coronary angiography was acquired at
      12.5 and 25 f/sec after 200 mug of intracoronary glyceryl trinitrate. Results of
      the corrected TIMI frame count (cTFC) at 12.5 and 25 f/sec for each vessel were:
      right coronary artery, 19.5 +/- 5.2 and 20.4 +/- 6.6 (P = 0.15); circumflex
      artery, 25.6 +/- 8.2 and 25.9 +/- 8.7 (P = 0.5); and left anterior descending
      artery, 22.5 +/- 8.1 and 23.8 +/- 10.4 (P = 0.15), respectively. The mean
      difference in the TFC between two injections by the same operator and by two
      operators was 0.4 (P = 0.7) and 0.4 (P = 0.2), respectively. The mean difference
      in the TFC for repeat measurements by the same observer and between two observers
      was 0.26 (P = 0.3) and 0.06 (P = 0.8), respectively. We confirm that the cTFC is
      a quantitative method to assess coronary flow that can be applied in a modern
      digital laboratory.

PMID- 15558770
TI  - New device for percutaneous closure of aortopulmonary collaterals.
AB  - A 4.5-month-old infant with tetralogy of Fallot, pulmonary atresia, and multiple
      aortopulmonary collaterals underwent successful occlusion of the collaterals
      using a new device. This new plug (Amplatzer vascular plug) is a self-expandable
      cylindrical device made of nitinol wire mesh. The device is available in sizes
      from 4 to 16 mm in 2 mm increment. The device can be used in patients with
      aortopulmonary collaterals, pulmonary arteriovenous malformations, venovenous
      collaterals, shunts, coronary fistulas, and certain type of patent ductus
      arteriosus.

PMID- 15558771
TI  - Thrombosis after septal closure device placement: a review of the current
      literature.
AB  - Thrombus formation has been described for all types of commercially available
      transcatheter septal occlusion devices. Most reports have been single-institution
      case studies. Screening for hypercoagulable conditions prior to device placement
      and anticoagulation after device deployment has been variable. The objective of
      this study was to synthesize the current experience with device thrombosis; the
      Medline database from 1980 until 2004 was searched. Seventeen articles identified
      54 unique patients with device thrombosis. Thrombus developed on eight different
      types of transcatheter devices. All commercially available devices had at least
      one reported case of thrombosis. Patient mean age was 44.2 +/- 9.8 years.
      Thrombosis was diagnosed at a mean of 5 months after device deployment. Prior to
      device placement, 12 patients had normal coagulation evaluations and 5 had
      coagulopathies. For 37 patients, no mention was made in the report of coagulation
      studies. Prior to device thrombosis, 26 patients received aspirin and
      clopidogrel, 15 patients received aspirin alone, 8 received warfarin, 2 heparin
      alone, 1 aspirin and warfarin. One patient with hemophilia A received no
      anticoagulation and in one case treatment prior to thrombosis was not reported.
      After device thrombosis, 35 patients were treated with warfarin with thrombus
      resolution, 2 had successful lytic therapy, 1 was treated with heparin alone.
      Sixteen patients had surgical explantation of the device. Septal occlusion device
      thrombosis is rare. All types of commercially available devices have been
      associated with thrombosis. All patients should have early (< or = 3 months)
      echocardiographic surveillance for device thrombosis. Thorough coagulation
      evaluation is imperative prior to transcatheter device placement.

PMID- 15558772
TI  - SCAI and Cordis partner to offer research fellowships in interventional
      corporation cardiology.

PMID- 15558774
TI  - Validation of a new formula for mean arterial pressure calculation: the new
      formula is superior to the standard formula.
AB  - Mean arterial pressure (MAP) has traditionally been derived from systolic and
      diastolic pressures, weighted 1/3 systolic and 2/3 diastolic. No correction is
      made for the increasing time dominance of systole with increasing heart rates. In
      a previous study, we developed a new and more accurate heart rate-corrected MAP
      formula from central aorta pressure determinations in a large number of patients:
      MAP = DP + [0.33 + (HR x 0.0012)] x [PP] where SP and DP are systolic and
      diastolic pressure and HR is heart rate. The current study validates the new MAP
      formula in the same patient at increasing paced heart rates. A central aorta
      catheter was used to obtain computer-determined systolic, diastolic, and MAP in
      12 patients. Values were obtained at baseline and then at increasing right atrial
      paced heart rates. The new and standard MAP formula-derived values were compared
      with computer-determined values. The new formula showed a much closer correlation
      with the computer-derived values for MAP. Standard MAP calculations for MAP can
      easily be improved by inclusion of a heart rate factor.

PMID- 15558775
TI  - Use of suture-mediated vascular closure devices for the management of femoral
      vein access after transcatheter procedures.
AB  - Groin complications remain the most common complication of cardiac
      catheterization procedures. While the use of closure devices is increasing for
      arterial sheaths, venous sheaths tend to be removed and hemostasis achieved with
      manual compression. We report our experience using Perclose suture-mediated
      vascular closure device to achieve hemostasis and early mobility in patients who
      have had venous access as part of their procedure. There were a total of 42
      patients (21 males; average age, 63.5 years) studied. The majority of the
      patients had 7 Fr sheaths (24), with access sites of sheaths up to 14 Fr being
      closed with this technique. Two patients developed complications at the access
      site: one patient requiring rehospitalization for intravenous antibiotics because
      of late access site infection, and one patient with deep venous thrombosis and
      pulmonary emboli. We conclude that the use of the Perclose suture-mediated
      closure device for closure of femoral venous access sites is feasible and should
      be considered especially in patients with larger venous sheaths and those at
      increased risk of groin complications.

PMID- 15558776
TI  - Successful use of the frontrunner catheter in the treatment of in-stent coronary
      chronic total occlusions.
AB  - Percutaneous intervention of coronary chronic total occlusion (CTO) from in-stent
      restenosis (ISR) is hindered by difficulty to cross the lesion with conventional
      guidewires. This study describes the successful treatment of five cases of CTOs
      from ISR using the Frontrunner controlled blunt microdissection catheter. Four of
      the five cases had failed previous attempts of percutaneous intervention with
      conventional guidewires. The Frontrunner catheter successfully facilitated the
      placement of guidewire into the distal true lumen in all five cases. The median
      crossing time was 10 min. No subintimal delivery of guidewire or vascular
      perforation was observed. TIMI 3 flow was achieved in all target vessels after
      further balloon angioplasty or stenting. The Frontrunner device is a safe and
      effective tool in the treatment of CTOs from ISR.

PMID- 15558777
TI  - Penetrating might be easier than retrieving.

PMID- 15558778
TI  - New path for teaching anatomy: living anatomy and medical imaging vs. dissection.

PMID- 15558779
TI  - Dissection laboratory is vital to medical gross anatomy education.

PMID- 15558780
TI  - Prosection vs. dissection, the debate continues: rebuttal to Granger.

PMID- 15558781
TI  - Anatomy of attentional networks.
AB  - Attention is a central theme in psychological science. As with other biological
      systems, attention has a distinct anatomy that carries out basic psychological
      functions. Disparate attentional networks correlate with discrete neural
      circuitry and can be influenced by specific brain injuries, states, and drugs.
      Accordingly, thinking about attention as an organ system is advantageous for
      understanding the details of this complex cognitive process. In the context of an
      influential model of attention, this article introduces the broad notion of
      attention, then addresses its prominent characteristics, mechanisms, and
      theories. The presentation emphasizes the role of recent neuroimaging data in
      outlining the functional neuroanatomy subserving distinct attentional networks. A
      discussion of pertinent results connects attentional networks with self
      regulation, development, and rehabilitation training.

PMID- 15558782
TI  - Ultrastructural evidence for a direct excitatory pathway from the nucleus
      retroambiguus to lateral longissimus and quadratus lumborum motoneurons in the
      female golden hamster.
AB  - During mating, the female golden hamster displays a stereotyped specific
      receptive posture, characterized by lordosis of the back, elevation of the tail,
      and extension of the legs. Muscles involved in this posture are thought to be
      iliopsoas, cutaneus trunci, lateral longissimus (LL), and quadratus lumborum
      (QL). Lesion studies in rats suggest that mating behavior is controlled by the
      mesencephalic periaqueductal gray (PAG). The PAG does not project directly to the
      motoneurons innervating the muscles involved in mating, but is thought to make
      use of the nucleus retroambiguus (NRA) as relay. The NRA is located
      ventrolaterally in the most caudal medulla, and projects directly to iliopsoas
      and cutaneus trunci motoneuronal cell groups. The question is whether this is
      also true for LL and QL muscles. Retrograde HRP tracing experiments revealed that
      LL and QL motoneurons are located medially in the ventral horn of the T12-L6 and
      T13-L4 segments, respectively. A subsequent ultrastructural study combined
      wheatgerm agglutinin-conjugated horseradish peroxidase injections in the NRA with
      cholera-toxin B-subunit injections in LL and QL muscles. The results revealed
      monosynaptic contacts between anterogradely labeled NRA-fiber terminals with
      retrogradely labeled dendrites of both LL and QL motoneurons. Almost all these
      terminals had asymmetrical synapses and contained spherical vesicles, suggesting
      an excitatory function of this NRA-motoneuronal pathway. These results correspond
      with the hypothesis that in hamster the PAG-NRA-motoneuronal projection not only
      involves motoneurons of iliopsoas and cutaneus trunci but also of LL and QL.

PMID- 15558783
TI  - TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation
      and nonneuronal cells.
AB  - Neurotrophin-activated receptor tyrosine kinases (Trks) regulate sensory neuron
      survival, differentiation, and function. To permanently mark cells that ever
      express TrkC-kinase, mice with lacZ and GFP reporters of Cre recombinase activity
      were crossed with mice having IRES-cre inserted into the kinase-containing exon
      of the TrkC gene. Prenatal reporter expression matched published locations of
      TrkC-expression. Postnatally, more trigeminal neurons and types of mystacial pad
      innervation expressed reporter than immunodetectable TrkC, indicating that some
      innervation transiently expresses TrkC-kinase. Reporter-tagged neurons include
      all those that immunolabel for TrkC, a majority for TrkB, and a small proportion
      for TrkA. TrkA neurons expressing TrkC-reporter range from small to large size
      and supply well-defined types of mystacial pad innervation. Virtually all small
      neurons and C-fiber innervation requires TrkA to develop, but TrkC-reporter is
      present in only a small proportion that uniquely innervates piloneural complexes
      of guard hairs and inner conical bodies of vibrissa follicle-sinus complexes.
      TrkC-reporter is expressed in nearly all presumptive Adelta innervation, which is
      all eliminated in TrkA knockouts and partially eliminated in TrkC knockouts. Many
      types of Abeta-fiber innervation express TrkC-reporter including all Merkel,
      spiny, and circumferentially oriented lanceolate endings, and some reticular and
      longitudinally oriented lanceolate endings. Only Merkel endings require TrkC to
      develop and survive, whereas the other endings require TrkA and/or TrkB. Thus,
      TrkC is required for the existence of some types of innervation that express
      TrkC, but may have different functions in others. Many types of nonneuronal cells
      affiliated with hair follicles and blood vessels also express TrkC-reporter but
      lack immunodetectable TrkC.

PMID- 15558784
TI  - Differential subcellular localization of cholesterol, gangliosides, and
      glycosaminoglycans in murine models of mucopolysaccharide storage disorders.
AB  - The mucopolysaccharidoses (MPSs) are a complex family of lysosomal storage
      disorders characterized by failure to degrade heparan sulfate (HS) and/or other
      types of glycosaminoglycans (GAGs) secondary to the absence of specific lysosomal
      enzymes. An accompanying storage of glycosphingolipids (GSLs), most notably GM2
      and GM3 gangliosides, has also been documented to occur in many types of MPS
      disease and is believed to be caused by secondary inhibition of GSL-degradative
      enzymes by intracellular GAG accumulation. We have documented the presence of
      secondary ganglioside accumulation in mouse models of several MPS disorders
      (types I, IIIA, IIIB, and VII) and report that this storage is accompanied by
      sequestration of free cholesterol in a manner similar to that observed in primary
      gangliosidoses. Using confocal microscopy, we evaluated the cellular distribution
      of cholesterol, GM2 and GM3 gangliosides, and HS in brains of mice with MPS IIIA
      disease. Unexpectedly, we found that although both gangliosides often accumulated
      in the same neurons, they were consistently located in separate populations of
      cytoplasmic vesicles. Additionally, GM3 ganglioside only partially co-localized
      with the primary storage material (HS), and cholesterol likewise only partially
      co-localized with the GM2 and GM3 gangliosides. These findings raise significant
      questions about the mechanism(s) responsible for secondary accumulation of
      storage materials in MPS disease. Furthermore, given that GSLs and cholesterol
      are constituents of membrane rafts believed critical in signal transduction
      events in neurons, their co-sequestration in individual neurons suggests the
      presence of defects in the composition, trafficking, and/or recycling of raft
      components and thus possible new mechanisms to explain neuronal dysfunction in
      MPS disorders.

PMID- 15558785
TI  - Quantitative analysis of neuronal morphologies in the mouse retina visualized by
      using a genetically directed reporter.
AB  - An alkaline phosphatase (AP) reporter has been used to visualize detailed
      morphologies for all major classes of retinal neurons in the adult mouse. The
      analysis was performed on retinas in which AP expression was activated by Cre
      mediated DNA recombination in a small fraction of cells. Recombination was
      controlled pharmacologically and, to a first approximation, appears to have
      occurred randomly. The morphologies of 794 inner retinal neurons have been
      analyzed by measuring arbor area, stratification level, and neurite branching
      patterns. When analyzed in this multidimensional parametric space, the cells can
      be clustered into subgroups by visual inspection and by using the Ward's and K
      means algorithms. One application of this cell morphology data set and cluster
      analysis is as a standard for comparison with the retinas of genetically altered
      mice. This work illustrates the utility and feasibility of genetically directed
      marking methods for large-scale surveys of neuronal morphology.

PMID- 15558786
TI  - Mammaglobin and CRxA-01 in pleural effusion cytology: potential utility of
      distinguishing metastatic breast carcinomas from other cytokeratin 7
      positive/cytokeratin 20-negative carcinomas.
AB  - BACKGROUND: The most common causes of malignant pleural effusions in women are
      metastatic lung carcinomas and breast carcinomas. It is often very difficult to
      distinguish between breast carcinomas and other metastatic carcinomas when they
      share a similar morphology and a similar cytokeratin profile (CK7-positive/CK20
      negative [CK7+/CK20-]). To better differentiate between metastatic mammary
      carcinomas and other metastatic carcinomas in pleural effusion cytology, the
      authors studied the potential use of a novel antibody, CRxA-01, which was
      identified by a cDNA subtraction library, together with a well characterized
      antibody against mammaglobin. METHODS: A computer search for patients with
      malignant pleural effusion specimens between January 1992 and November 2002
      generated 228 patients, 71 of whom had cell block material and a known clinical
      history. Primary malignancies among these patients included 20 breast carcinomas,
      32 lung carcinomas, 4 endometrial carcinomas, 9 ovarian carcinomas, 4
      gastrointestinal carcinomas, and 2 genitourinary carcinomas. All specimens were
      immunostained with anti-CK7, CK20, CRxA-01, and mammaglobin antibodies. Only CK7
      positive/CK20-negative (CK7+/CK20-) specimens were included in the current study,
      and only definitive membranous staining for CRxA-01 and cytoplasmic staining for
      mammaglobin were considered to be positive. RESULTS: For patients with metastatic
      breast carcinomas, mammaglobin was positive in 11 of 20 (55%) tissue specimens
      and CRxA-01 was positive in 12 of 20 (60%) tissue specimens. When CRxA-01 and
      mammaglobin were used together, 16 of 20 (80%) tissue specimens were positive for
      mammaglobin or/and CRxA-01 antibodies. This staining pattern was not seen for
      tissue specimens from patients with other metastatic carcinomas. Two of 4 (50%)
      uterine carcinoma specimens and 6 of 9 (67%) ovarian carcinoma specimens were
      positive for CRxA-01 only. CONCLUSIONS: CRxA-01 and mammaglobin were expressed in
      most metastatic breast carcinoma specimens. Other CK7+/CK20- carcinoma specimens
      did not express mammaglobin and showed weak or negative staining for CRxA-01.
      When used together, CRxA-01 and mammaglobin greatly improved the sensitivity and
      specificity for the detection of metastatic breast carcinoma in pleural effusion
      specimens.

PMID- 15558787
TI  - Monkey business: how primates see, hear, and smell the world around them.

PMID- 15558788
TI  - Dissection in learning and teaching gross anatomy: rebuttal to McLachlan.

PMID- 15558789
TI  - Dissection from the Spanish anatomist's perspective: aims, attitudes, and related
      aspects.
AB  - We present the results of a study conducted on participants of the 21st Congress
      of the Spanish Society of Anatomy, in which anatomists were asked their opinions
      about a range of issues related to anatomical dissection: its relative roles as
      the exclusive source of anatomy teaching, as a source for medical research, or to
      assist the future professional to acquire emotional control; the attitudes and
      behaviors they expect the student to have in the dissecting room; whether the
      student-cadaver relationship can convey knowledge and attitudes affecting the
      future doctor-patient relationship; and the anatomists' attitudes toward
      donation. Anatomists considered dissection to be mainly an instrument for
      professional training and to help develop professional skills. They gave little
      importance to the role it could play in helping students to control their
      emotions. However, this aspect was considered to be more important by anatomists
      who also valued a close doctor-patient relationship. On the other hand, a
      majority of anatomists felt that the student's attitude and behavior during
      dissection could be to some extent reflected in future relationships with
      patients. However, they did not feel that dissection-related attitudes would
      distinguish between future good or bad doctors. Finally, anatomy teachers are
      generally in favor of donation (86.5%), especially of organs alone (52.7%), and
      this aspect was not affected by their religious beliefs.

PMID- 15558790
TI  - To what extent is cadaver dissection necessary to learn medical gross anatomy? A
      debate forum.

PMID- 15558791
TI  - Idiopathic thrombocytopenic purpura associated with bone marrow sea-blue
      histiocytosis.

PMID- 15558792
TI  - Simultaneous occurrence of paroxysmal nocturnal hemoglobinuria and chronic
      lymphocytic leukemia.

PMID- 15558793
TI  - Reciprocal relationship between a Ph-negative clone with trisomy 8 associated
      with severe myelodysplasia and a Ph-positive clone following imatinib treatment
      in a patient with accelerated-phase chronic myelogenous leukemia (CML).

PMID- 15558794
TI  - The incremental effect of positron emission tomography on diagnostic accuracy in
      the initial staging of esophageal carcinoma.
AB  - BACKGROUND: The purpose of the current study was to assess whether
      [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) provides
      incremental value (e.g., additional information on lymph node involvement or the
      presence of distant metastases) compared with computed tomography (CT) in
      patients with esophageal carcinoma. METHODS: The authors examined 149 consecutive
      patients with thoracic esophageal carcinoma. Eighty-one patients underwent
      radical esophagectomy without pretreatment, 17 received chemoradiotherapy
      followed by surgery, 3 underwent endoscopic mucosal resection, and the remaining
      48 patients received definitive radiotherapy and chemotherapy. The diagnostic
      accuracy of FDG-PET and CT was evaluated at the time of diagnosis. RESULTS: The
      primary tumor was visualized using FDG-PET in 119 (80%) of 149 patients.
      Regarding lymph node metastases, FDG-PET had 32% sensitivity, 99% specificity,
      and 93% accuracy for individual lymph node group evaluation and 55% sensitivity,
      90% specificity, and 72% accuracy for lymph node staging evaluation. PET
      exhibited incremental value over CT with regard to lymph node status in 14 of 98
      patients who received surgery: 6 patients with negative CT findings were
      eventually shown to have lymph node metastases (i.e., they had positive PET
      findings and a positive reference standard [RS]); 6 patients with positive CT
      findings were shown not to have lymph node metastases (i.e., they had negative
      PET findings and a negative RS); and 2 patients were shown to have cervical lymph
      node metastases in addition to mediastinal or abdominal lymph node metastases.
      Among the remaining patients, PET showed incremental value over CT with regard to
      distant organ metastases in six patients. The overall incremental value of PET
      compared with CT with regard to staging accuracy was 14% (20 of 149 patients).
      CONCLUSIONS: FDG-PET provided incremental value over CT in the initial staging of
      esophageal carcinoma. At present, combined PET-CT may be the most effective
      method available for the preoperative staging of esophageal tumors.

PMID- 15558795
TI  - Overproduction of BCR-ABL induces apoptosis in imatinib mesylate-resistant cell
      lines.
AB  - BACKGROUND: Imatinib mesylate, a BCR-ABL tyrosine kinase inhibitor, induces
      apoptosis in chronic myeloid leukemia cells. Resistance to imatinib is currently
      the most important concern of this treatment. One of the main mechanisms of this
      resistance is overexpression of BCR-ABL. METHODS: In the current study, the
      authors investigated the correlation between BCR-ABL overexpression and apoptosis
      in BaF/BCR-ABL and LAMA84 cell lines resistant to imatinib suddenly deprived of
      the inhibitor, and compared with their sensitive counterpart. RESULTS: Removal of
      imatinib from culture medium led to a decrease in Bcr-Abl protein expression by
      Day 5, which was sustained for > or = 3 weeks of imatinib deprivation. Apoptosis
      was observed after 3 days of imatinib deprivation in resistant lines accompanied
      by caspase activation, loss of membrane asymmetry (annexin V staining), and
      alteration of mitochondrial potential (dihexyloxacarbocyanine iodide [DiOC6]).
      Transient activation of the STAT5/Bcl-xL pathway and Akt kinase activity preceded
      these responses. CONCLUSIONS: Thus, imatinib removal led to apoptosis of BCR-ABL
      overexpressing leukemic cells, a phenomenon that could be exploited to sensitize
      imatinib-resistant cells to the cytotoxic effect of other drugs.

PMID- 15558796
TI  - Appropriateness of breast-conserving treatment of breast carcinoma in women with
      germline mutations in BRCA1 or BRCA2: a clinic-based series.
AB  - BACKGROUND: Although BRCA1 and BRCA2 were identified in 1994 and 1995,
      respectively, to the authors' knowledge the optimal management of women with BRCA
      associated breast carcinoma remains incompletely defined. The current study
      evaluates the appropriateness of breast-conserving therapy (BCT) in women with
      BRCA mutations. METHODS: Between May 1992 and October 2003, 87 female
      participants in genetic testing protocols were identified who 1) were found to
      have deleterious germline BRCA mutations and 2) reported a history of invasive
      breast carcinoma that was treated with wide local excision and radiation therapy.
      Clinical records were reviewed and follow-up was updated. RESULTS: The 87
      subjects underwent BCT for 95 invasive breast tumors (8 women received BCT for
      metachronous bilateral tumors). In all 95 treated breasts, the 5-year and 10-year
      probabilities of metachronous ipsilateral breast carcinoma (MIBC) were 11.2% and
      13.6%, respectively. Among the 87 subjects, the 5-year and 10-year probabilities
      of metachronous contralateral breast carcinoma (CBC) after treatment of the index
      tumor were 11.9% and 37.6%. No clinical factors were identified that were
      associated with either MIBC or CBC, including the use of tamoxifen or
      chemotherapy. CONCLUSIONS: Women with BRCA-associated breast carcinoma who
      undergo BCT appear to have risks of MIBC that are similar to those reported for
      young women without known mutations. The indications for unilateral mastectomy in
      this group of women should be the same as those for women with nonhereditary
      carcinoma. However, significant risks of CBC and possibly late MIBC may prompt
      the serious consideration of bilateral mastectomy as a preventive measure.

PMID- 15558798
TI  - Commissural propriospinal connections between the lateral aspects of laminae III
      IV in the lumbar spinal cord of rats.
AB  - It has been established that there is a strong functional link between sensory
      neural circuits on the two sides of the spinal cord. In one of our recent studies
      we provided a morphological confirmation of this functional phenomenon,
      presenting evidence for the presence of a direct commissural connection between
      the lateral aspects of the dorsal horn on the two sides of the lumbar spinal
      cord. By using a combination of neural tracing and immunocytochemical detection
      of neural markers like vesicular glutamate transporters, glutamic acid
      decarboxylase, glycine transporter, and met-enkephalin (which are characteristic
      of various subsets of excitatory and inhibitory neurons), we investigated here
      the distribution, synaptic relations, and neurochemical characteristics of the
      commissural axon terminals. We found that the cells of origin of commissural
      fibers in the lateral aspect of the dorsal horn were confined to laminae III-IV
      and projected to the corresponding area of the contralateral gray matter. Most of
      the commissural axon terminals established synaptic contacts with dendrites.
      Axospinous or axosomatic synaptic contacts were found in limited numbers. We
      demonstrated that interactions among commissural neurons also exist. More than
      three-fourths of the labeled axon terminals were immunostained for glutamic acid
      decarboxylase and/or glycine transporter, but none of them showed positive
      immunoreaction for met-enkephalin and vesicular glutamate transporters. The
      results indicate that there is a substantial reciprocal commissural synaptic
      interaction between the lateral aspects of laminae III-IV on the two sides of the
      lumbar spinal cord and that this pathway may transmit both inhibitory and
      excitatory signals to their postsynaptic targets.

PMID- 15558799
TI  - Alpha7 but not alpha4 AChR subunit expression is regulated by light in developing
      primary visual cortex.
AB  - In the present paper we analyzed the expression pattern of the alpha4 and alpha7
      nicotinic acetylcholine receptor (nAChR) subunits in the rat visual cortex
      through postnatal development, to clarify whether their expression is
      developmentally regulated and whether eventual developmental changes are
      regulated by visual experience. We found that both alpha4 and alpha7 mRNA levels
      accumulate from postnatal day 12 (P12) before eye opening, to around P35. The
      immunohistochemical results indicated that both subunits are expressed throughout
      all cortical laminae, except layer I. Alpha4 subunit immunohistochemistry
      revealed significant increments in the number of positive cells in layers V and
      VI after eye opening. In the case of the alpha7 subunit, the number of
      immunoreactive cells increased in all cortical layers soon after eye opening,
      except in layer VI, matching the results found at the transcriptional level. In
      animals reared in darkness from P9 to P22, the relative amount of the alpha4 mRNA
      and the number of immunoreactive cells exhibited no changes. 3H-epibatidine
      binding experiments showed that the number of heteromeric nAChR subunits in dark
      reared rats did not change with respect to age-matched controls, thus confirming
      the immunohistochemical results. The mRNA of the alpha7 subunit remained stable
      in dark-reared rats, whereas the number and distribution of immunoreactive cells
      changed. Moreover, the number of 125I alphabungarotoxin-binding nAChRs was
      significantly increased in dark-reared animals. These results indicate that
      visual cortex stimulation by visual input is an essential step for alpha7 nAChR
      normal expression, suggesting a possible role for these receptors in an
      experience-dependent fashion on the maturation of this cortical area.

PMID- 15558800
TI  - Determination of iron in blood serum using flow injection with luminol
      chemiluminescence detection.
AB  - A simple and rapid fl ow injection method is reported for the determination of
      iron in blood serum after acid digestion with HNO3 and HClO4, based on luminol CL
      detection in the absence of added oxidant. The detection limit (3 s) was 1.0
      nmol/L with a sample throughput of 120/h. The calibration graph was linear over
      the range 0.001-1.0 micromol/L (r2 = 0.9974), with relative standard deviations
      (RSD) (n = 4) in the range 3.2-5%. The effect of interfering cations (Ca(II),
      Mg(II), Cu(II), Cd(II), Pb(II), Mn(II), Zn(II), Ni(II), Co(II) and Fe(III)) and
      anions (Cl-, SO4(2-), HCO3-, NO3-, NO2-) were studied using a luminol CL system
      for Fe(II) determination. The method was applied to normal blood serum and the
      results (1.32 +/- 0.08-1.74 +/- 0.05 mg/L) were compared with those from a
      spectrophotometric reference method (1.34 +/- 0.06-1.80 +/- 0.10 mg/L), which
      agree fairly well with the overall reference range in blood.

PMID- 15558801
TI  - Fire fly luciferin as antioxidant and light emitter: the evolution of insect
      bioluminescence.
AB  - Insects are the main group with luminescent species among terrestrial animals. In
      this paper, we report that fire fly luciferin is endowed with antioxidant
      properties against oxidative and nitrosative stress. The luciferin reduces
      linoleate peroxidation in acellular tests and increases the viability of
      mammalian cells exposed to the oxidant tert-butyl hydroperoxide. Dehydrorhodamine
      based tests indicate that fire fly luciferin also scavenges peroxynitrite,
      whereas parallel tests on cells showed a marked protection of cells subjected to
      the peroxynitrite generator SIN-1. Together, these results suggest that fire fly
      luciferin's antioxidant properties could help photocytes coping with the
      hyperoxidant conditions to which they are submitted during luminous emissions.
      These data could also suggest that the evolutionary foundation of the
      bioluminescent system could have been the luciferin, and not the luciferase,
      first serving as a scavenger of oxidants toxic to the cells, then as a light
      emitting substrate for luciferase precursors. Similarities with the evolutionary
      scenario proposed for marine bioluminescent organisms relying on coelenterazine
      suggest that the surprisingly high success rate observed in the independent
      emergence of bioluminescent animals could reflect the ease of transformation of
      antioxidant mechanisms into light-producing systems.

PMID- 15558802
TI  - Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant
      glioma.
AB  - BACKGROUND: In the current study, the authors report a Phase II trial of
      irinotecan (CPT-11), a topoisomerase I inhibitor active against malignant glioma
      (MG), with celecoxib, a selective COX-2 inhibitor, among MG patients with
      recurrent disease. METHODS: Patients with MG at any type of recurrence received
      CPT-11, administered as a 90-minute intravenous infusion on Weeks 1, 2, 4, and 5
      of each 6-week cycle plus celecoxib, which was administered continuously at a
      dose of 400 mg twice a day. CPT-11 was given at a dose of 350 mg/m(2) for
      patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and at a dose of
      125 mg/m(2) for those patients not receiving EIAEDs. Assessments were performed
      after every cycle. The primary endpoint was radiographic response and the
      secondary endpoints were progression-free survival (PFS), overall survival (OS),
      and therapeutic safety. RESULTS: Thirty-four of the 37 patients enrolled in the
      current study (92%) were diagnosed with recurrent GBM and 3 patients (8%) were
      diagnosed with recurrent anaplastic astrocytoma (AA). Twenty-one patients were
      receiving EIAEDs and 16 patients were not. The median follow-up time was 76.9
      weeks. Concomitant CPT-11 plus celecoxib was found to be well tolerated and safe.
      Hematologic toxicities of >/= Grade 3 (according the second version of the Common
      Toxicity Criteria of the National Cancer Institute) reportedly complicated 8.6%
      of treatment courses. Grade 3 diarrhea, the most commonly reported nonhematologic
      toxicity, occurred with equal frequency (8%), regardless of whether the patient
      was receiving EIAED. Six patients (16%), all whom were diagnosed with recurrent
      GBM, achieved an objective radiographic response whereas an additional 13
      patients (35%) achieved stable disease. The median PFS was 11.0 weeks and the 6
      month PFS was reported to be 25.1%. The median OS was 31.5 weeks. CONCLUSIONS:
      The results of the current study confirm that CPT-11 plus celecoxib can be safely
      administered concurrently at full dose levels, and that this regimen has
      encouraging activity among heavily pretreated patients with recurrent MG.

PMID- 15558803
TI  - Influence analysis for linear mixed-effects models.
AB  - In this paper, we extend several regression diagnostic techniques commonly used
      in linear regression, such as leverage, infinitesimal influence, case deletion
      diagnostics, Cook's distance, and local influence to the linear mixed-effects
      model. In each case, the proposed new measure has a direct interpretation in
      terms of the effects on a parameter of interest, and collapses to the familiar
      linear regression measure when there are no random effects. The new measures are
      explicitly defined functions and do not necessitate re-estimation of the model,
      especially for cluster deletion diagnostics. The basis for both the cluster
      deletion diagnostics and Cook's distance is a generalization of Miller's simple
      update formula for case deletion for linear models. Pregibon's infinitesimal case
      deletion diagnostics is adapted to the linear mixed-effects model. A simple
      compact matrix formula is derived to assess the local influence of the fixed
      effects regression coefficients. Finally, a link between the local influence
      approach and Cook's distance is established. These influence measures are applied
      to an analysis of 5-year Medicare reimbursements to colon cancer patients to
      identify the most influential observations and their effects on the fixed-effects
      coefficients.

PMID- 15558804
TI  - Factors affecting choice of hemostatic agent for the hemophilia patient with an
      inhibitor antibody.
AB  - Achieving adequate hemostasis in patients with hemophilia and high-titer
      inhibitor antibodies remains a challenge despite the development of plasma
      derived and recombinant therapies to bypass the inhibitory effect. A group of
      hemophilia treaters met to examine the factors that influence physician choices
      among the very costly and cumbersome available therapies. Specific knowledge
      deficits in need of prospective research were identified with respect to the
      rational treatment of inhibitor patients.

PMID- 15558805
TI  - Successful high-titer immunoglobulin therapy for persistent parvovirus B19
      infection in a lymphoma patient treated with rituximab-combined chemotherapy.
AB  - A 40-year-old female diagnosed with follicular lymphoma was treated with
      rituximab-combined chemotherapy. Although she achieved complete remission, she
      developed progressive anemia and reticulocytopenia. Bone marrow examination
      revealed features of pure red cell aplasia and hemophagocytosis. In addition, the
      appearance of large pronormoblasts suggested that she was infected with
      parvovirus B19. Excess viral DNA in her bone marrow confirmed that her illness
      was caused by persistent parvovirus B19 infection. Serum immunoglobulin levels
      decreased beyond the lower normal limit, which indicated that her humoral
      immunity was impaired after rituximab-combined chemotherapy. Although she had
      been infected with parvovirus B19, she was re-infected and failed to control the
      viral expansion. High-titer immunoglobulin against parvovirus B19 was
      intravenously administrated and resulted in remarkable reticulocytosis and
      improvement of anemia. High-titer immunoglobulin, which contained a sufficient
      amount of neutralizing antibodies against parvovirus B19, likely inactivated most
      viruses in vivo. We successfully eradicated the virus after 2 courses of high
      dose therapy at 0.5 g/kg/day every week followed by 8 courses of maintenance
      therapy at 0.1 g/kg/day every other week. It is important to consider that
      parvovirus B19 infection is a possible cause of progressive anemia in B-cell
      lymphoma patients treated with rituximab-combined chemotherapy. We propose that
      the use of high-titer immunoglobulin against parvovirus B19 may enable such
      immunocompromised patients to eradicate the virus before sufficient immune system
      reconstruction.

PMID- 15558806
TI  - Nonmyeloablative allogeneic bone marrow transplantation for treatment of
      myelodysplastic syndrome complicated by recent intracerebral hemorrhage.
AB  - A patient with intracerebral hemorrhage is considered ineligible for
      hematopoietic stem cell transplantation (HSCT). We report a 49-year-old woman
      with myelodysplastic syndrome (MDS) complicated by refractoriness to platelet
      transfusion and intracerebral hemorrhage, who underwent allogeneic bone marrow
      transplantation from an HLA-identical unrelated male donor. Nine days before the
      scheduled transplantation, she developed dysarthria and right hemiparesis;
      computed tomography (CT) of the brain disclosed an acute hematoma in the left
      parietal lobe exceeding 3 cm in diameter. She underwent conditioning with reduced
      intensity, including fludarabine (30 mg/m2/day on days -8 to -3), busulfan (4
      mg/kg/day on days -6 and -5), and total body irradiation (4 Gy on day -2). Two
      weeks after transplantation, dysarthria and right hemiparesis began to resolve,
      and CT showed spontaneous resolution of the hematoma. Simultaneously, engraftment
      was confirmed. Thus, recent stroke may be not an absolute contraindication for
      HSCT.

PMID- 15558807
TI  - Hydroxyurea-induced hemolytic anemia in a patient with essential thrombocythemia.
AB  - Hydroxyurea (HU) has been used in patients with essential thrombocythemia (ET) to
      reduce the frequency and severity of thrombotic complications of the disease. It
      acts by causing bone marrow depression, resulting in a decrease in platelet and
      leukocyte counts and in anemia with megaloblastosis. Herein we report a case of
      an 80-year-old man with ET who developed severe hemolytic anemia requiring
      multiple packed RBC transfusions while being treated with HU. The hemolysis
      persisted until discontinuation of the drug. This case suggests hemolysis as a
      potential side effect of HU and raises the clinical concern that not all HU
      induced anemia is secondary to erythropoiesis depression. With the increasing use
      of HU in the management of ET, hemoglobinopathy, and other diseases, the
      importance of monitoring for hemolysis must be further emphasized in these
      patients.

PMID- 15558808
TI  - Phase relationships and thermodynamic interactions of isotactic poly(1-butene)
      and organic solvent systems.
AB  - Isotactic crystalline low-molecular-weight poly(1-butene), iPBu-1, was
      synthesised by using a metallocene catalyst. The molecular weight was determined
      by GPC. The chemical structure of iPBu-1 was verified by using high-temperature
      (13)C NMR spectroscopy and the thermal properties by differential scanning
      calorimetry (DSC). The (solid+liquid) equilibria, SLE, of iPBu-1 with different
      hydrocarbons (n-hexadecane, 1-heptene, 1-heptyne, cyclopentane, cyclohexane,
      cycloheptane, cyclooctane, benzene and propylbenzene) were studied by a dynamic
      method. By performing these experiments over a large concentration range, the
      temperature-mole fraction phase diagrams of the polymer-solvent systems could be
      constructed. From these diagrams it was found that iPBu-1 had the highest
      solubility in small-ring cycloalkanes and the lowest in n-hexadecane, 1-heptyne
      and benzene in the mole fraction range measured. The excess Gibbs energy models
      were used to describe the nonideal behaviour of the liquid phase and to estimate
      the solubility of iPBu-1 in the whole mole fraction range. Activity coefficients
      at infinite dilution of polymer and solvent were determined from the solubility
      measurements and were predicted by using the UNIFAC FV model and molecular Monte
      Carlo simulations.

PMID- 15558809
TI  - The correlation between fatigue, physical function, the systemic inflammatory
      response, and psychological distress in patients with advanced lung cancer.
AB  - BACKGROUND: Functional disability is reported frequently in fatigued cancer
      patients, but little is known about the correlation between fatigue and objective
      physical function. In addition, from previous work, the systemic inflammatory
      response and psychological distress appear to be related to fatigue. METHODS:
      Thirty-eight patients with metastatic or locally advanced lung carcinoma and 15
      age-matched and gender-matched, healthy controls completed the Functional
      Assessment of Chronic Illness Therapy-Fatigue scale, a visual analogue weakness
      score, and the Hospital Anxiety and Depression (HAD) scale. Hemoglobin
      concentrations, C-reactive protein (CRP) concentrations, creatine kinase
      concentrations, white blood cell count, body composition, Karnofsky performance
      status (KPS), grip strength, and chair-rise time also were measured in both
      groups. The cancer patients were then grouped into tertiles on the basis of
      fatigue scores. RESULTS: The cancer patients had greater fatigue compared with
      the control group (P < 0.001). They also weighed less, had lower hemoglobin and
      creatine kinase levels and higher CRP levels, and had lower KPS, poorer grip
      strength, longer chair-rise times, and increased HAD scale scores (all P < 0.01).
      KPS and chair-rise time were correlated strongly (r(2) = 0.565; P < 0.001). With
      increasing fatigue, KPS was lower, and chair-rise time and HAD scale scores were
      greater (P < 0.01). On multiple regression analysis, only KPS, weakness, and HAD
      scale scores were correlated independently with fatigue (r(2) = 0.570; P <
      0.001). CONCLUSIONS: Objective physical function (as measured by chair-rise time)
      in patients with advanced lung cancer was poorer with increasing fatigue. Results
      of the current study suggest that fatigue is not a result primarily of weight
      loss or anemia but is related to KPS and psychological distress.

PMID- 15558810
TI  - Re: Accuracy of pharmacy records.

PMID- 15558812
TI  - A challenge to the data miners.

PMID- 15558813
TI  - Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma
      cells.
AB  - BACKGROUND: DNA damage sensor proteins have received much attention as upstream
      components of the DNA damage checkpoint signaling pathway that are required for
      cell cycle control and the induction of apoptosis. Deficiencies in these proteins
      are directly linked to the accumulation of gene mutations, which can induce
      cellular transformation and result in malignant disease. METHODS: Using 48 sets
      of tumor tissue specimens and peripheral normal lung tissue specimens from 48
      patients with nonsmall cell lung carcinoma (NSCLC) who underwent surgery, the
      authors investigated the expression of hRad9 protein, a member of the human DNA
      damage sensor family, using immunohistochemical and Western blot analyses.
      RESULTS: Immunohistochemical analysis detected the accumulation of hRad9 in the
      nuclei of tumor cells in 16 tumor tissue specimens, (33% of tumor tissue
      specimens examined). Western blot analysis also revealed elevated levels of
      phosphorylated hRad9 protein in NSCLC cells that was accompanied by the detection
      of phosphorylated Chk1, a protein kinase that regulates the downstream signaling
      of the DNA damage checkpoint pathway. Furthermore, strong expression of hRad9 was
      correlated with an increase in Ki-67 expression index in the tumor cells that
      were examined. CONCLUSIONS: The findings made in the current study suggest that
      Rad9 expression may play an important role in cell cycle control in NSCLC cells
      and may influence NSCLC cell phenotype.

PMID- 15558814
TI  - Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and
      gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial.
AB  - BACKGROUND: Gemcitabine has broad activity in a variety of solid tumors including
      biliary tract carcinomas. The authors evaluated 6-month survival, response, and
      toxicity associated with a combination of gemcitabine, 5-fluorouracil (5-FU), and
      leucovorin (LV) in patients with unresectable or metastatic biliary tract or
      gallbladder adenocarcinoma (ACA). METHODS: A 4-week course included 1000 mg/m2
      gemcitabine by intravenous infusion over 30 minutes on Days 1, 8, and 15, 25
      mg/m2 LV by intravenous push, and 600 mg/m2 5-FU by intravenous push after LV.
      RESULTS: Forty-two patients were enrolled in 6 months, 35 of whom had metastatic
      disease. Patients with biliary tract ACA included 24 with hepatic disease (19
      patients had intrahepatic disease and 5 patients had extrahepatic disease) and 4
      with disease in the ampulla of Vater. All patients were evaluable and received a
      median of 4 courses of treatment (range, 1-21 courses). Commonly occurring severe
      toxicity (NCI CTC Grade 3 or worse) included: dyspnea (four patients), nausea
      (four patients), fatigue (seven patients), thrombocytopenia (six patients),
      emesis (four patients), and diarrhea (four patients). Five partial responses
      (9.5%) occurred, 3 of which were sustained for > or = 8 weeks. No treatment
      related deaths occurred. Thirty-two patients had disease progression and 38 died
      after a median follow-up of 20 months (range, 1.4-24 months). The median time to
      disease progression was 4.6 months (95% confidence interval [95% CI], 2.4-6.6%).
      The median survival period was 9.7 months (95% CI, 7-12%). CONCLUSIONS: This
      combination regimen was manageable in patients with advanced biliary tract and
      gallbladder ACA. Of 42 patients, 24 (57%) survived > or = 6 months, satisfying
      the primary end point of the trial. The length of survival suggested that
      gemcitabine, 5-FU, and LV had benefit equivalent to gemcitabine alone.

PMID- 15558815
TI  - Society of Urologic Oncology position statement: redefining the management of
      hormone-refractory prostate carcinoma.
AB  - Because patients with hormone-refractory prostate carcinoma are a very diverse
      group, management of these patients represents a unique challenge. Despite much
      research, to the authors' knowledge few studies published to date have provided
      definitive treatment answers. The Society of Urologic Oncology (SUO) convened a
      multidisciplinary panel of urologists, oncologists, and radiation oncologists to
      develop a treatment algorithm for patients with hormone-refractory prostate
      carcinoma. The resulting treatment outline was based on a review of the
      literature review and on the expert opinions of the panelists. The current
      article provided a logical progression of treatment choices that included
      hormonal manipulations, chemotherapeutic options, and adjunctive therapies.
      Future clinical trials and therapies were also discussed by the authors.
      Management strategies should be targeted toward the individual patient. Although
      significant progress has been made in understanding and treating hormone
      refractory prostate carcinoma, earlier interventions would be ideal and better
      therapeutic approaches to prolong survival are necessary.

PMID- 15558816
TI  - The Bacillus megaterium comE locus encodes a functional DNA uptake protein.
AB  - From Bacillus megaterium, a genomic region was isolated and structurally
      characterized which strongly resembles the Bacillus subtilis competence locus
      comE encoding proteins involved in DNA uptake. Functionality of the B. megaterium
      comEA gene was proven by complementing a DNA-receptor mutant of B. subtilis. This
      finding provides first evidence for a latent ability of B. megaterium to develop
      natural competence, although such physiological state has not as yet been
      identified in this organism.

PMID- 15558817
TI  - Unusual properties of the prespore-specific enzyme, UDPgalactose:polysaccharide
      galactosyl transferase, of Dictyostelium discoideum.
AB  - UDPgalactose:polysaccharide galactosyl-transferase is the enzyme that is
      specifically localized in prespore cells of Dictyostelium discoideum and its
      activity sharply changes in response to differentiation and dedifferentiation. To
      clarify the nature of this enzyme, we first developed an improved assay method
      for the enzyme, and by using this method, we partially purified the enzyme
      through DEAE-sepharose, phenyl-sepharose and ATP-sepharose chromatography. The
      apparent molecular mass of the enzyme was ca. 200 KDa (by non-denaturing
      polyacrylamide gel gradient analysis) and the isoelectric point was around pH 7.
      The enzyme exhibited a hitherto undescribed property, that is the reaction
      proceeds faster at 0 degrees C than at 21 degrees C, with a smaller K(m) value
      and an unchanged V(max) value. This low-temperature resistant property of the
      enzyme is consistent with the previous observation (Maeda 1984, J. Cell Sci. 69,
      159-165) that prespore differentiation is favored at low temperatures. The
      reaction appears to proceed in a double displacement manner. ATP reversibly
      inhibited the enzyme with a K(i) value of 2 mM, suggesting the possibility that
      ATP regulates its activity in vivo.

PMID- 15558818
TI  - Species identification and comparative molecular and physiological analysis of
      Candida zemplinina and Candida stellata.
AB  - Strains of the recently described yeast species Candida zemplinina have been
      identified in botrytized grapes and musts in geographically distant areas. C.
      zemplinina is almost indistinguishable from C. stellata, another yeast common in
      fermenting botrytized wines. In this work a specific PCR-RFLP method is described
      for the differentiation of the two species. It is also shown that both species
      have three chromosomes, display chromosomal length polymorphism, and C.
      zemplinina has a smaller genome. C. zemplinina is acidogenic, highly
      osmotolerant, grows much better than C. stellata in the presence of ethanol and
      at low temperatures.

PMID- 15558819
TI  - Comparison of Botryosphaeran production by the ascomyceteous fungus
      Botryosphaeria sp., grown on different carbohydrate carbon sources, and their
      partial structural features.
AB  - The influence of glucose concentration and other carbohydrates (monosaccharides:
      fructose, galactose, mannose; polyols: mannitol and sorbitol; disaccharides:
      lactose, sucrose and commercial sucrose; and industrial sugarcane molasses) were
      compared as sole carbon sources for the production of Botryosphaeran, an
      exopolysaccharide (EPS) produced by Botryosphaeria sp. The optimum glucose
      concentration for EPS production was 50 g l(-1). With the exception of mannitol,
      the fungus produced EPS on all carbon sources studied, with highest yields
      occurring with sucrose followed by glucose. All EPS showed exclusively glucose
      after acid hydrolysis and monosaccharide analysis. FTIR spectroscopy demonstrated
      the presence of beta-anomers indicating that all the EPS produced by
      Botryosphaeria sp. on the different carbon sources were essentially of the beta-D
      glucan type.

PMID- 15558820
TI  - Direct observation of hydrogen molecules adsorbed onto a microporous coordination
      polymer.

PMID- 15558821
TI  - Fatigue is becoming an exhausting problem.

PMID- 15558822
TI  - Selection of cultivation medium for production of late stationary phase serine
      proteinases from Bacillus intermedius.
AB  - B. intermedius have been shown previously to secrete two serine proteinases:
      glutamyl endopeptidase 2 and subtilisin 2 during the late stationary phase, with
      maximal levels of the enzymes activities recorded at the 40th and 44th hours of
      growth, respectively. In the current study, we analyzed the impact of various
      culture medium components on biosynthesis of these proteinases. Yeast extract and
      gelatin did not stimulate the enzymes biosynthesis. However, on the medium
      containing 0.1% casein subtilisin 2 production increased to reach 140%.
      Biosynthesis of both serine proteinases, produced by B. intermedius at the late
      stationary phase, were found to be inhibited by individual amino acids, and to be
      insensitive to catabolite repression. In order to maximise enzyme production, the
      presence of Ca(2+) and Mg(2+) at concentration of 5 mM was shown to be necessary.
      Based on the results of this work, the composition of a complex culture media for
      the effective production of late stationary phase proteinases by B. intermedius
      was developed.

PMID- 15558823
TI  - Indirect identification of isoprenoid quinones in Escherichia coli by LC-MS with
      atmospheric pressure chemical ionization in negative mode.
AB  - A novel analytical method was applied for identification of isoprenoid quinones
      in Escherichia coli by liquid chromatography atmospheric press chemical
      ionization mass spectrometry in negative mode (LC-NI-APCI-MS). Extraction and
      clean-up of sample were carried out on Sep-Pak Plus Silica solid-phase extraction
      cartridges. Ubiquinone-7 (UQ-7), Ubiquinone-8 (UQ-8) and Mequinone-8 (MK-8) were
      determined directly using combined information on retention time, molecular ion
      mass, fragment ion masses and UV characteristic spectrometry without any standard
      reagent. It was found that UQ-8 was the major component of isoprenoid quinones in
      Escherichia coli under aerobic condition. Compared with UQ-8, the relative
      abundance of UQ-7 and MK-8 is only 15% and 14%, respectively. The average
      recoveries of UQ-6, UQ-10 and vitamin K(1) in Escherichia coli were investigated
      by standard spiking experiment. The recoveries were achieved in the range from 94
      to 106%, and the relative standard deviations (RSD) of the triplicate analysis of
      the spiked samples (UQ-6, UQ-10 and vitamin K(1)) ranged from 3 to 8%. The
      detection limits of LC-NI-APCI-MS were estimated to be 5, 40 and 0.8 microg/g dry
      cell for UQ-6, UQ-10 and vitamin K(1), respectively.

PMID- 15558824
TI  - Diversity and abundance of Bacteria and Archaea in the Bor Khlueng Hot Spring in
      Thailand.
AB  - The prokaryotic diversity in the Bor Khlueng hot spring in Ratchaburi province,
      Thailand was investigated by a culture-independent molecular approach. This
      hydrothermal pool is located in the central part of Thailand and contains sulfide
      rich mineral water that is believed to relieve muscle ache and pain. The water
      flow year-round with temperature ranging between 50-57 degrees C. Community DNA
      was extracted directly from sediment samples by coring to depth of approximately
      20-30 cm. Small-subunit rRNA genes (16S rDNA) were amplified by PCR using primers
      specific for the domains Archaea and Bacteria. The PCR products were cloned and
      sequenced. For the bacterial rDNA clone library, 200 clones were randomly
      selected for further analyses. After restriction fragment length polymorphism
      (RFLP) analysis of rDNA clones and exclusion of chimeric sequences 36 phylotypes
      were obtained. The Bor Khlueng phylotypes spanned a wide range within the domain
      Bacteria, occupying eleven major lineages (phyla). Almost a quarter (23%) of the
      clones were classified as Acidobacteria. The other clones were grouped into the
      Bacteriodetes (19%), Nitrospirae (13%), Proteobacteria (12%), Deinococcus-Thermus
      lineage (11%), planctomycetes (6%), and Verrucomicrobia (5%). The four remaining
      phyla, 5% each, were assigned to Actinobacteria, Chloroflexi, Cyanobacteria, and
      the candidate division "OP10". For the archaeal 16S rRNA gene sequence library,
      25 distinct phylotypes were obtained, 17 clones were found to be associated with
      Crenarahaeota and 8 clones were associated with Euryarachaeota. The findings of
      the molecular survey of this so far not investigated site showed that Bor Khlueng
      hot spring is a potential rich source of unique bacterial and archaeal species.
      The great majority ( approximately 80%) of the prokaryotic sequences detected in
      Bor Khlueng were unknown.

PMID- 15558825
TI  - Comparative evaluation of the Desoxycholate Agar Nissui Food Stamp and swab
      methods for estimating coliform organisms in poultry processing plants after
      cleaning in Japan.
AB  - Bacterial control in poultry processing plants is very important, but the swab
      method for estimating bacterial contamination is somewhat troublesome in routine
      work. We compared the Desoxycholate Agar Nissui Food Stamp (DA-NFS) based on the
      agar contact method with the swab method to estimate coliform organisms from
      various equipments in four poultry processing plants after cleaning. Overall 104
      surfaces for coliform organisms were evaluated. The results from 98 (94.2%)
      surfaces for coliform organisms were equivalent by the DA-NFS and swab methods
      and there were no significant differences between two methods (P > 0.05). The
      correlation coefficient between the DA-NFS and swab methods was 0.91. We conclude
      that the DA-NFS could be useful for routine coliform organisms examination in
      poultry processing plants after cleaning in Japan.

PMID- 15558826
TI  - Delayed haematological complications of mustard gas.
AB  - Haematopoiesis could be affected by mustard gas. We randomly selected 318
      chemical victims exposed to mustard gas and compared their cell blood counts and
      peripheral blood smears (PBS) with those of 377 healthy men, and also various
      haematological indices of 57 of these victims compared with previous data 5 years
      ago. The average number of red blood cells and haemoglobin of victims compared
      with the controls was not significantly different, but they were increased
      compared with data from 5 years ago. White blood cell counts, neutrophils and
      lymphocytes did not show any clinically meaningful difference compared with the
      control group but 20 cases with atypical lymphocytes in their PBS have been
      found. Change in lymphocyte shape may be related to committed stem cell
      involvement. Further studies on bone marrow cells and cell markers are needed to
      document this hypothesis. The mild increase in erythroid cells and haemoglobin
      concentration may be due to chronic obstructive pulmonary disorder and other
      respiratory diseases in these patients.

PMID- 15558827
TI  - Protection and inflammatory markers following exposure of guinea pigs to sarin
      vapour: comparative efficacy of three oximes.
AB  - The purpose of the present study was to compare the antidotal efficacy and the
      combined effects on inflammatory markers of three oximes--toxogonine, TMB4 and 2
      PAM--in combination with anticholinergic drugs following exposure to sarin vapour
      by inhalation. Guinea pigs restrained in plethysmographs were exposed to various
      doses of sarin vapour (in the range of 1.4-4.4LD50). The antidotal mixture was
      injected immediately (5-20 s) following exposure (3 mg kg(-1) atropine and 1 mg
      kg(-1) benactyzine in combination with 6 mg kg(-1) toxogonine, 2 mg kg(-1) TMB4
      or 12 mg kg(-1) 2-PAM). Bronchoalveolar lavage (BAL) samples were taken from
      surviving animals 24 h after exposure to determine the levels of inflammatory
      markers. A differential cell count was performed in BAL samples on Giemsa-stained
      slides. The inflammatory markers--histamine and prostaglandins (PGE)--were
      measured in BAL using radioimmunoassay (RIA) techniques. The survival rate in the
      various treatment groups and analysis of BAL samples showed that: (i) Toxogonine,
      TMB4 and 2-PAM, without pyridostigmine pretreatment, at doses that were
      proportional to their doses in the respective auto-injectors, exhibited similar
      antidotal efficacy against sarin exposure. (ii) The results demonstrated that a
      centrally acting anticholinergic drug is essential in the antidotal mixture to
      ensure survival. (iii) Histamine release and eosinophilia following sarin
      inhalation might require additional intervention, aimed at reducing the symptoms
      of allergic reaction and possibly expediting recovery.

PMID- 15558828
TI  - Liver microsomal biotransformation of nitro-aryl drugs: mechanism for potential
      oxidative stress induction.
AB  - Toxic effects of several nitro-aryl drugs are attributed to the nitro-reduction
      that may be suffered in vivo, a reaction that may be catalysed by different
      reductases. One of these enzymes is NADPH-cytochrome P450 reductase, which
      belongs to the cytochrome P450 oxidative system mainly localized in the
      endoplasmic reticulum of the hepatic cell. This system is responsible for the
      biotransformation of oxidative lipophilic compounds, so that oxidative and
      reductive metabolic pathways of lipophilic nitro-aryl drugs can take place
      simultaneously. Because of the affinity of nitro-aryl drugs (xenobiotics) for the
      endoplasmic reticulum, we propose this subcellular organelle as a good biological
      system for investigating the toxicity induced by the biotransformation of these
      or another compounds. In this work we used rat liver microsomes to assess the
      oxidative stress induced by nitro-aryl drug biotransformation. Incubation of
      microsomes of rat liver with nifurtimox and nitrofurantoin in the presence of
      NADPH induced lipoperoxidation, UDP-glucuronyltransferase activation and an
      increase in the basal microsomal oxygen consumption. Nitro-aryl-1,4
      dihydropyridines did not elicit these prooxidant effects; furthermore, they
      inhibited lipoperoxidation and oxygen consumption induced by Fe3+/ascorbate.
      Nifurtimox and nitrofurantoin modified the maximum absorption of cytochrome P450
      oxidase and inhibited p-nitroanisole O-demethylation, an oxidative reaction
      catalysed by the cytochrome P450 system, signifying that oxidation may proceed in
      a similar way to that described for nitro-aryl-1,4-dihydropyridines. Thus the
      balance between lipophilic nitro-aryl drug oxidation and reduction may be
      involved in the potential oxidative stress induced by biotransformation.

PMID- 15558829
TI  - Anemia and childhood mortality: latitudinal patterning along the coast of pre
      Columbian Peru.
AB  - Hrdlicka ([1914] Smithson. Inst. Misc. Collect. 61:1-69) reported that pre
      Columbian skeletal material from the coastal lowland Andean region exhibited a
      high frequency of porotic hyperostosis, a pathological condition of bone that
      generally is thought to indicate childhood anemia. While subsequent studies
      tended to reinforce this conclusion, factors implicated in the condition have yet
      to be fully explored in the region as a whole. This study explores regional and
      intravalley variation as one step in establishing biocultural variables that
      increase the apparent risk of childhood anemia. The study sample includes 1,465
      individuals: 512 from Peruvian collections housed at the Field Museum of Natural
      History, and 953 from systematically excavated contexts from Moquegua, Peru.
      Environmental stressors, such as parasites and disease, rather than specific
      dietary practices were found to be more likely associated with childhood anemia
      in these coastal Andean samples. The study supports cribra orbitalia as an
      earlier expression of porotic hyperostosis and suggests that porotic
      hyperostosis, as recorded here, cannot be easily dismissed as a result of cranial
      shape modification. No clear temporal patterns were observed. Finally, the study
      establishes that comparing data for children and adults can reveal the relative
      association between childhood anemia and mortality. Childhood mortality
      associated with anemia was elevated where the presence of tuberculosis or
      tuberculosis-like conditions was more common and the presence of water-borne
      pathogens was negligible. In contrast, those buried at lower altitudes, closer to
      the coast, and consuming mainly marine resources were less likely to die in
      childhood with anemia than in the other contexts studied.

PMID- 15558830
TI  - Is there a "most chiral tetrahedron"?
AB  - A degree of chirality is a function that purports to measure the amount of
      chirality of an object: it is equal for enantiomers, vanishes only for achiral or
      degenerate objects and is similarity invariant, dimensionless and normalisable to
      the interval [0,1]. For a tetrahedron of non-zero three-dimensional volume,
      achirality is synonymous with the presence of a mirror plane containing one edge
      and bisecting its opposite, and hence it is easy to design degree-of-chirality
      functions based on edge length that incorporate all constraints. It is shown that
      such functions can have largest maxima at widely different points in the
      tetrahedral shape space, and by incorporation of appropriate factors, the maxima
      can be pushed to any point in the space. Thus the phrase "most chiral
      tetrahedron" has no general meaning: any chiral tetrahedron is the most chiral
      for some legitimate choice of degree of chirality.

PMID- 15558831
TI  - Non-parametric estimation of the odds ratios for continuous exposures using
      generalized additive models with an unknown link function.
AB  - The generalized additive, model (GAM) is a powerful and widely used tool that
      allows researchers to fit, non-parametrically, the effect of continuous
      predictors on a transformation of the mean response variable. Such a
      transformation is given by a so-called link function, and in GAMs this link
      function is assumed to be known. Nevertheless, if an incorrect choice is made for
      the link, the resulting GAM is misspecified and the results obtained may be
      misleading. In this paper, we propose a modified version of the local scoring
      algorithm that allows for the non-parametric estimation of the link function, by
      using local linear kernel smoothers. To better understand the effect that each
      covariate produces on the outcome, results are expressed in terms of the non
      parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the
      bias in the OR estimation and to construct point-wise confidence intervals. A
      simulation study was carried out to assess the behaviour of the resulting
      estimates. The proposed methodology was illustrated using data from the AIDS
      Register of Galicia (NW Spain), with a view to assessing the effect of the CD4
      lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis
      (TB). This application shows how the link's flexibility makes it possible to
      obtain OR curve estimates that are less sensitive to the presence of outliers and
      unusual values that are often present in the extremes of the covariate
      distributions.

PMID- 15558832
TI  - Treatment comparisons for a partially categorical outcome applied to a biomarker
      with assay limit.
AB  - The plasma level of HIV-RNA has been shown to be a strong prognostic biomarker
      for clinical progression and death in HIV infected patients and is widely used as
      the primary outcome in clinical trials to evaluate antiretroviral treatments.
      Currently approved assays to measure HIV-RNA levels have a lower limit of
      reliable quantification (LoQ). Current regulatory guidelines recommend using the
      proportion of patients achieving HIV-RNA levels below the assay limit at a
      certain time point (e.g. 24 or 48 weeks) as the primary endpoint for regulatory
      approval. However, a substantial decrease in HIV-RNA that does not go below the
      LoQ still is considered clinically beneficial for patients with advanced diseases
      who have failed many other therapies and are unlikely to maximally suppress the
      virus and achieve HIV-RNA levels below the LoQ. An experimental treatment may not
      be distinguishable from a control solely in terms of the proportions of patients
      whose HIV-RNA levels fall below the LoQ. The sensitivity of the comparison
      between the experimental treatment and the control could be increased by
      considering as well the difference between the treatments with respect to the HIV
      RNA reductions of patients not achieving HIV-RNA levels below the LoQ. In this
      paper, we introduce a best-rank analysis which assigns the best rank to patients
      who achieve the HIV-RNA levels below the LoQ and applies the Mann-Whitney
      Wilcoxon rank test to compare the two treatment groups. The Mann-Whitney-Wilcoxon
      statistic is shown to be a weighted sum of two statistics: one to compare the
      proportions of patients achieving the HIV-RNA levels below the LoQ and one to
      compare the viral reductions in patients with HIV-RNA levels above the LoQ. The
      corresponding statistical null and alternative hypotheses and the clinical
      interpretations of this best-rank test procedure are also discussed. An example
      is used to illustrate this approach and a simulation study is used to compare
      this approach with other methods.

PMID- 15558833
TI  - Protective role of melatonin in ochratoxin a toxicity in rat heart and lung.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by different fungi. The most
      pronounced adverse effect of OTA is hepatonephrotoxicity. Melatonin (MEL) has an
      antioxidant effect and has free-radical scavenger properties. The effects of OTA
      on heart and lung tissue and possible ameliorating effects of MEL were
      investigated in rats. Twenty-four rats were allocated to three groups (each with
      eight rats): control; OTA-treated group (OTA dose 289 microg kg(-1) per day); and
      OTA + MEL-treated group (MEL dose 10 mg kg(-1) per day). After 30 days of
      treatment, the histopathological changes in the heart and lung of all groups were
      examined. Compared with the control rats, myocardial tissue of rats treated with
      OTA showed extensive cytoplasmic vacuole formation, necrosis of the myocytes,
      dissolution of the nucleus, clumped fibres, fibrillolysis, swollen myocardial
      fibres, small haemorrhagic areas and hyperaemic vessels (P <0.05). In addition,
      lungs of rats treated with OTA showed alveolar congestion, alveolar cell
      hyperplasia, prominent alveolar septal vessels, variable intensity loss of
      alveolar architecture, intraparenchymal inflammatory infiltration,
      intraparenchymal hyperaemic vessels, respiratory epithelial proliferation,
      perivascular and peribronchial inflammation, pneumonic infiltration, distorted
      appearance of lung parenchyma and emphysematous areas (P <0.05). In comparison
      with the OTA groups, the ameliorating effects of MEL in the lung damage
      parameters were on alveolar cell hyperplasia, prominent alveolar septal vessels,
      variable intensity loss of alveolar architecture, intraparenchymal inflammatory
      infiltration, perivascular inflammatory inflammation, distorted appearance of
      lung parenchyma and focal emphysematous areas in lung (P <0.05). Melatonin also
      significantly reduced myocardial damage in most of the parameters: extensive
      cytoplasmic vacuole formation, necrosis of the myocytes, clumped fibres,
      fibrillolysis, small haemorrhagic areas and hypaeremic vessels in heart (P
      <0.05). On the other hand, MEL did not lower the degree of damage in lung and
      heart to the level of the control rats, except for the parameters of the
      interstitial oedema and small haemorrhagic areas only in myocardial tissue.
      Histopathological findings showed that OTA induced damage in heart and lung and
      MEL treatment significantly reduced the degree of damage.

PMID- 15558834
TI  - Low levels of sarin affect the EEG in marmoset monkeys: a pilot study.
AB  - The main purpose of this pilot study was to estimate the lowest observable
      adverse effect level (LOAEL) for the electroencephalogram (EEG) upon long-term,
      low-level exposure of vehicle-pretreated and pyridostigmine-pretreated marmoset
      monkeys to sarin vapour. This is the C.t value (t=5 h) of exposure at which the
      EEG becomes significantly different from that resulting from air exposure of the
      same animals. The LOAELs for effects on the EEG in vehicle- and pyridostigmine
      pretreated marmosets appeared to be 0.2 and 0.1 mg min m(-3), respectively.
      Comparatively, the latter LOAEL values are at least an order of magnitude lower
      than the previously established LOAEL for miosis and only 2-5 times higher than
      the lowest observable effect level (LOEL) of bound sarin in blood. The second aim
      of the study was to analyse the EEG of the same marmosets again during a 5-h
      exposure to air 1 year after exposure to sarin vapour. All the marmosets still
      demonstrated significant (P <0.05) EEG differences. In most vehicle-pretreated
      marmosets the energy (microV2) per EEG band was higher than that observed 1 year
      earlier, which might indicate that neurons had become more sensitive to
      excitation. This phenomenon was less pronounced in pyridostigmine-pretreated
      animals. Visual examination of the EEG records revealed clear bursts of alpha
      frequencies (ca. 9 Hz), resembling sleep-spindles, that were present more
      frequently in both groups of exposed marmosets than in naive animals. These late
      changes in spindle oscillation might be the result of changes in the cholinergic
      system due to exposure to sarin vapour 1 year previously. In conclusion, EEG
      abnormalities persisting for more than 1 year may occur in humans during long
      term (5 h) exposure to subclinical levels of sarin that are not detectable by the
      currently fielded alarm systems.

PMID- 15558835
TI  - Factors that identify survival after liver retransplantation for allograft
      failure caused by recurrent hepatitis C infection.
AB  - Hepatitis C virus (HCV) is becoming the most common indication for liver
      retransplantation (ReLTx). This study was a retrospective review of the medical
      records of liver transplant patients at our institution to determine factors that
      would identify the best candidates for ReLTx resulting from allograft failure
      because of HCV recurrence. The patients were divided into 2 groups on the basis
      of indication for initial liver transplant. Group 1 included ReLTx patients whose
      initial indication for LTx was HCV. Group 2 included patients who received ReLTx
      who did not have a history of HCV. We defined chronic allograft dysfunction (AD)
      as patients with persistent jaundice (> 30 days) beginning 6 months after primary
      liver transplant in the absence of other reasons. HCV was the primary indication
      for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%)
      from July 1996 to February 2004. The number of patients with AD undergoing ReLTx
      in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft
      survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The
      rates of primary nonfunction and technical problems after ReLTx were not
      different between the groups. However, the incidence of recurrent AD was higher
      in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that
      predicted a successful ReLTx included physical condition at the time of ReLTx (P
      = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is
      associated with an increased incidence of chronic graft destruction with a
      negative effect on long-term results after ReLTx. The optimum candidate for ReLTx
      is a patient who can maintain normal physical activity. As the allograft shortage
      continues, the optimal use of cadaveric livers continues to be of primary
      importance. The use of deceased donor livers in patients with allograft failure
      caused by HCV remains a highly controversial issue.

PMID- 15558836
TI  - UW is superior to Celsior and HTK in the protection of human liver endothelial
      cells against preservation injury.
AB  - Celsior solution (CS), a new preservation solution in thoracic organ
      transplantation, was evaluated for its efficacy in cold preservation of human
      liver endothelial cells (HLEC) and was compared to University of Wisconsin
      solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol).
      HLEC cultures were preserved at 4 degrees C in CS, UW, and HTK, for 2, 6, 12, 24,
      and 48 hours, with 6 hours of reperfusion. Levels of lactate dehydrogenase (LDH),
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and adenosine
      5'-triphosphate (ATP) were measured after each interval of ischemia and the
      respective phase of reperfusion. Preservation injury of HLEC as measured by LDH
      release, intracellular ATP level, and MTT reduction were overall significantly (P
      <or= .01, P <or= .01, P < .05, respectively) lower in UW than in CS and HTK. CS
      demonstrates a modest superiority to HTK in HLEC preservation. Furthermore, cold
      preservation remains the main cause of preservation injury of HLEC regardless of
      the preservation solution used. Additionally, the maintenance of a high
      intracellular ATP level of HLEC after ischemia and reperfusion, as shown by UW,
      could be taken as a beneficial effect, particularly in long-term ischemia. In
      conclusion, our cell culture model reveals the order of efficacy to protect HLEC
      against preservation injury as: UW >> CS > HTK.

PMID- 15558837
TI  - A simple hybrid variance estimator for the Kaplan-Meier survival function.
AB  - In this paper, we propose a hybrid variance estimator for the Kaplan-Meier
      survival function. This new estimator approximates the true variance by a
      Binomial variance formula, where the proportion parameter is a piecewise non
      increasing function of the Kaplan-Meier survival function and its upper bound, as
      described below. Also, the effective sample size equals the number of subjects
      not censored prior to that time. In addition, we consider an adjusted hybrid
      variance estimator that modifies the regular estimator for small sample sizes. We
      present a simulation study to compare the performance of the regular and adjusted
      hybrid variance estimators to the Greenwood and Peto variance estimators for
      small sample sizes. We show that on average these hybrid variance estimators give
      closer variance estimates to the true values than the traditional variance
      estimators, and hence confidence intervals constructed with these hybrid variance
      estimators have more nominal coverage rates. Indeed, the Greenwood and Peto
      variance estimators can substantially underestimate the true variance in the left
      and right tails of the survival distribution, even with moderately censored data.
      Finally, we illustrate the use of these hybrid and traditional variance
      estimators on a data set from a leukaemia clinical trial.

PMID- 15558838
TI  - Heterogeneity of CD80 gene transcription by human keratinocytes to allergens and
      irritants: relevance to allergic contact dermatitis in vivo.
AB  - Using an in vitro assay for CD80 promoter activity, the transcriptional response
      of primary cultured human keratinocytes from different donors in response to
      allergens and irritants was studied. The CD80 promoter activity was increased
      reproducibly after exposure to certain chemicals. The epithelial cell lines HeLa
      and HaCaT also increased CD80 transcriptional activity in response to exposure to
      a panel of different allergens and irritants. Normal or immortalized
      keratinocytes responded reproducibly with a unique pattern to a panel of
      chemicals in which the culture increases CD80 transcription after exposure to
      certain chemicals and has no increase in CD80 transcription after exposure to
      other chemicals. Some keratinocyte cultures responded positively to certain
      chemicals whereas others did not respond to the same chemicals. Cultured
      keratinocytes from 16 of 20 adult donors (80%) responded to nitrochlorobenzene in
      vitro by increasing CD80 transcriptional activity, thus predicting subsequent
      sensitization to this same hapten (chi2= 7.2, P <0.0073). Thus, a keratinocyte
      CD80 gene expression assay exhibits good sensitivity in predicting allergic
      contact dermatitis for sensitizers such as dinitrochlorobenzene. These data
      suggest that there is a rationale for developing the use of gene-transcription
      based predictive assays to identify individual susceptibility to cutaneous
      reactivity after exposure to allergens and irritants.

PMID- 15558839
TI  - Pyridoxine (vitamin B6) neurotoxicity: enhancement by protein-deficient diet.
AB  - Large doses of pyridoxine cause injury to the primary sensory neurons in
      trigeminal and dorsal root ganglia of animals and patients subjected to
      megavitamin therapy. The increased hazard to subjects with reduced renal
      excretory function has been explored previously. In the present work, the
      neurotoxicity of pyridoxine for rats was found to be increased by dietary protein
      deficiency. A mere 3 or 7 days of pretreatment with either of two protein
      deficient diets were sufficient to accelerate and intensify the clinical
      neurological signs and histological lesions from pyridoxine injections. These
      results are caused, at least in part, by loss of body weight, decreased protein
      binding in serum and decreased consumption of water and decreased volume of
      urine, which reduce the urinary losses of the toxicant. The vitamers related to
      pyridoxine (pyridoxal, pyridoxamine) and the coenzyme (pyridoxal 5-phosphate) did
      not cause clinical signs or lesions similar to those produced by pyridoxine even
      when injected in maximum tolerated doses. Neither a protein-deficient diet nor
      bilateral nephrectomy changed the results with the vitamers.

PMID- 15558840
TI  - Gene therapy: lessons learned from liver transplantation for transthyretin
      amyloidosis.

PMID- 15558841
TI  - Hepatocellular proliferation and changes in microarchitecture of right lobe
      allografts in adult transplant recipients.
AB  - Imaging studies show complete restoration of liver volume in adult recipients of
      right lobe allografts within 2-3 weeks of living donor transplantation (LDLT).
      However, it is not known if this growth is associated with restoration of hepatic
      microarchitecture. We compared 21 biopsies without significant pathology from
      LDLT recipients with 23 biopsies from adult recipients of cadaveric donor liver
      transplantation (CDLT) performed within 3 months of transplantation. The
      difference in the number of portal tracts per cm was statistically significant (P
      < .0001) between CDLT (9.08 +/- 1.74) and LDLT recipients within 3 months (6.26
      +/- 1.62), as well as after 3 months following transplantation (6.56 +/- 1.44).
      The coefficient of correlation between length of biopsy specimens and the number
      of portal tracts in these 3 groups was .94, .93, and .85, respectively.
      Proliferative activity demonstrated by immunohistochemical staining for MIB-1 was
      seen predominantly in hepatocytes in both groups; bile ducts only occasionally
      stained positive. The difference between labeling indices of hepatocytes was
      statistically significant (P = .00056) between CDLT and LDLT recipients within 3
      months of transplantation (.82 +/- .63 and 4.53 +/- 3.72), and between LDLT
      recipients within 3 weeks and after 3 weeks of transplantation (5.97 +/- 3.78 and
      1.80 +/- 1.37, P = .0074). In conclusion, restoration of liver volume following
      LDLT occurs by proliferation of hepatocytes in the immediate posttransplant
      period. There is a decrease in number of portal tracts in these volume-restored
      allografts. Volume restoration is therefore, not accompanied by restoration of
      hepatic microarchitecture.

PMID- 15558842
TI  - Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1
      mutations.
AB  - Opitz syndrome (OS; MIM 145410 and MIM 300000) is a congenital midline
      malformation syndrome characterized by hypertelorism, hypospadias, cleft
      lip/palate, laryngotracheoesophageal (LTE) abnormalities, imperforate anus,
      developmental delay, and cardiac defects. The X-linked form (XLOS) is caused by
      mutations in the MID1 gene, which encodes a microtubule-associated RBCC protein.
      In this study, phenotypic manifestations of patients with and without MID1
      mutations were compared to determine genotype-phenotype correlations. We detected
      10 novel mutations, 5 in familial cases, 2 in sporadic cases, and 3 in families
      for whom it was not clear if they were familial or sporadic. The genotype and
      phenotype was compared for these 10 families, clinically diagnosed OS patients
      found not to have MID1 mutations, and 4 families in whom we have previously
      reported MID1 mutations. This combined data set includes clinical and mutation
      data on 70 patients. The XLOS patients with MID1 mutations were less severely
      affected than patients with MID1 mutations reported in previous studies,
      particularly in functionally significant neurologic, LTE, anal, and cardiac
      abnormalities. Minor anomalies were more prevalent in patients with MID1
      mutations compared to those without mutations in this study. Female MID1 mutation
      carriers had milder phenotypes compared to male MID1 mutation carriers, with the
      most common manifestation being hypertelorism in both sexes. Most of the
      anomalies found in the patients of the present study do not correlate with the
      MID1 mutation type, with the possible exception of LTE malformations. This study
      demonstrates the wide spectrum of severity and manifestations of OS. It also
      shows that XLOS patients with MID1 mutations may be less severely affected than
      indicated in prior reports.

PMID- 15558843
TI  - Phenolic glyscosides, a new class of human recombinant nucleotide pyrophosphatase
      phosphodiesterase-1 inhibitors.
AB  - Cytotoxicity and kinetic studies of phenolic glycosides, benzoyl salireposide (1)
      and salireposide (2), isolated from Symplocos racemosa, were performed against
      phosphodiesterase I enzyme from snake venom and human nucleotide pyrophosphatase
      phosphodiesterase-1. Lineweaver-Burk and Dixon plots and their secondary replots
      showed that these compounds are pure non-competitive inhibitors of both enzymes.
      K(i) Values of compounds 1 and 2 were found to be 360 and 1000 microM,
      respectively, against human nucleotide pyrophosphatase phosphodiesterase, and 525
      and 1100 microM, respectively, against snake venom phosphodiesterase. IC(50)
      values of compounds 1 and 2 are 90 microM +/- 0.04 and 383 microM +/- 0.03,
      respectively, against human nucleotide pyrophosphatase phosphodiesterase and 171
      microM +/- 0.02 and 544 microM +/- 0.021, respectively, against snake venom
      phosphodiesterase. Both compounds were found to be nontoxic up to concentration
      of 500 microM/mL as >90% cells were viable after 3 h of incubation. These
      compounds are potential candidates for the therapy of arthritis.

PMID- 15558844
TI  - A cancer clip from the Kentucky Cancer Registry at the University of Kentucky
      Markey Cancer Centers.

PMID- 15558845
TI  - [Problems in the clinical use of antibiotics in China].

PMID- 15558846
TI  - [Quality control of antimicrobial susceptibility testing by disk diffusion test].

PMID- 15558847
TI  - Mid-term follow-up after extracardiac Fontan operation.

PMID- 15558848
TI  - Predictors of change in low-density lipoprotein size during lipid-lowering
      treatment in type 2 diabetes.

PMID- 15558849
TI  - The Millennium Development Goals in the Americas.

PMID- 15558850
TI  - Country profiles. Ecuador.

PMID- 15558851
TI  - Country profiles. Guatemala.

PMID- 15558853
TI  - Case definitions. Schistosomiasis.

PMID- 15558852
TI  - Country profiles. Paraguay.

PMID- 15558855
TI  - The time is coming.

PMID- 15558854
TI  - Response to intra- and extracellular lipolytic agents and hormone-sensitive
      lipase translocation are impaired in adipocytes from rats adapted to a high
      protein, carbohydrate-free diet.
AB  - We showed previously that rats adapted to a high-protein (70%), carbohydrate-free
      (HP) diet have reduced lipolytic activity. To clarify the underlying biochemical
      mechanisms, several metabolic processes involved in adipose tissue lipolysis were
      investigated. The experiments were performed in rats adapted for 15 d to an HP or
      a balanced diet. In agreement with previous results, microdialysis experiments
      showed that the concentrations of adipose tissue interstitial and arterial plasma
      glycerol were lower in rats adapted to the HP diet. Under nonstimulated
      conditions, rates of lipolysis, estimated by glycerol release to the incubation
      medium, were reduced in adipocytes from HP rats. Under the same conditions, there
      was a small, but significant (17%) reduction in the activity of hormone sensitive
      lipase (HSL), with no change in the content of the enzyme. Upon stimulation with
      isoproterenol, the percentage of the enzyme in the adipocyte cytosol translocated
      to the fat droplet was 20-25%in HP rats and 40-50% in rats fed the balanced diet.
      Adipocytes from HP diet-adapted rats had a significantly reduced response
      (approximately 40%) to the lipolytic action of nonspecific (norepinephrine,
      epinephrine, isoproterenol) and specific (CL316,243, BRL37,344, dobutamine,
      clenbuterol) beta-adrenergic agonists. Adipocytes from HP rats also had a reduced
      lipolytic response to the intracellular agents, dibutyryl cAMP (44%), forskolin
      (46%), and isobutyl-methylxanthine (29%). The data suggest that the main
      mechanism responsible for the reduced basal and stimulated lipolysis in HP diet
      adapted rats is an impairment in the intracellular process of lipolysis
      activation, with a deficient translocation of HSL to the fat droplet.

PMID- 15558856
TI  - Vioxx risk could signify trouble in class.

PMID- 15558857
TI  - Better antibiotics through chemistry.

PMID- 15558858
TI  - Oppositions and appeals at the EPO.

PMID- 15558859
TI  - An audience with... Janet Woodcock discusses the role of the FDA in improving
      pharma productivity.

PMID- 15558860
TI  - Apoptosis-targeting therapies.

PMID- 15558861
TI  - Duloxetine hydrochloride.

PMID- 15558862
TI  - Flexible working attracts women to industry.

PMID- 15558863
TI  - [Speech for Professor Jean-Laurent Casanova. Award winner of the Dautrebande 2003
      prize].

PMID- 15558865
TI  - Should we welcome the end of the sick note?

PMID- 15558864
TI  - [Acute strabismus].

PMID- 15558866
TI  - Postcards: race and medicine in the 21st century.

PMID- 15558867
TI  - Assessment: harnessing change to improve standards.

PMID- 15558868
TI  - Abstracts of the 16th ECACGM (European Colloquium on Animal Cytogenetics and Gene
      Mapping). Jouy-en-Josas, France, July 6-9, 2004.

PMID- 15558869
TI  - Learning with Donald Rumsfeld - flexible learning: the relevance and resonance of
      multiprofessional learning in primary care.

PMID- 15558870
TI  - Excuses.

PMID- 15558871
TI  - Abstracts of the 38th Biennial American Cytogenetics Conference. April 22-25,
      Stevenson, Washington, USA.

PMID- 15558872
TI  - Digital psychiatry.
AB  - The American managed care movement has been viewed as a big experiment and is
      being watched closely by the rest of the world. In the meanwhile, computer-based
      information technology (IT) is changing the practice of medicine, much more
      rapidly than managed care. A New World of digitized knowledge and information has
      been created. Although literature on IT in psychiatry is largely absent in peer
      reviewed psychiatric journals, IT is finding its way into all aspects of
      medicine, particularly psychiatry. Telepsychiatry programs are becoming very
      popular. At the same time, medical information sites are flourishing and evolving
      into a new health-care industry. Patient-physician information asymmetry is
      decreasing as patients are gaining easy access to medical information hitherto
      only available to professionals. Thus, psychiatry is facing another paradigm
      shift, at a time when most attention has been focused on managed care. In this
      new digital world, knowledge and information are no longer the sole property of
      professionals. Value will migrate from traditional in-person office-based therapy
      to digital clinical products, from in-person library search and classroom
      didactic instruction to interactive on-line searches and distance learning. In
      this time of value migration, psychiatrists have to determine what their
      'distinctive competence' is and where best to add value in the health-care
      delivery value chain. The authors assess the impact of IT on clinical psychiatry
      and review how clinical practice, education and research in psychiatry are
      expected to change in this emerging digital world.

PMID- 15558873
TI  - Correlation dimension of the human sleep electroencephalogram.
AB  - Sleep electroencephalogram (EEG) was analyzed by nonlinear analysis.
      Polysomnography of a healthy male subject was analyzed and the correlation
      dimension was calculated. The mean correlation dimensions decreased from stage
      'awake' to stages 1, 2 and 3, and increased during rapid eye movement (REM)
      sleep. These results were also seen at every sleep cycle. During each sleep cycle
      the correlation dimensions decreased for slow wave sleep, then increased for REM
      sleep. The mean correlation dimension of the sleep EEG in the second half of the
      night was significantly higher than those in the first half of the night. A
      significant change was seen both during REM sleep as well as in sleep stage 2.
      Nonlinear analysis may be a useful method in the analysis of the entire sleep
      electroencephalogram.

PMID- 15558874
TI  - Characteristics of epilepsy in severely mentally retarded individuals.
AB  - In order to clarify the characteristics of epilepsy in patients with severe
      mentally retarded (SMR) subjects, we analyzed 52 SMR subjects with epilepsy from
      the institute for SMR subjects at Kikuchi National Hospital, Kumamoto, Japan. A
      total of 61.5% patients had uncontrolled seizures which were resistant to
      treatment. The most common combinations of seizure types in those not responding
      to conventional anticonvulsants were generalized tonic-clonic seizures (GTCS)
      with tonic seizure and GTCS with atypical absence. Their clinical features were
      characterized by spastic paralysis associated with a slower background
      electroencephalogram and abnormal computed tomography scans of the head,
      suggesting the involvement of cortical damage. These findings suggest that a
      large proportion of epilepsy in SMR subjects does not respond to treatment and
      that the severity of organic brain damage may therefore affect the natural course
      of epilepsy in such patients.

PMID- 15558875
TI  - Dipole source localization of interictal epileptiform activity in temporal lobe
      epilepsy with medial temporal lesion.
AB  - Dipole sources of interictal epileptiform activities recorded by conventional
      electroencephalogram (EEG) were estimated using the dipole tracing method. Four
      cases of temporal lobe epilepsy with medial temporal lesions were studied. Two
      patients with hippocampal sclerosis, one patient with granulation in the
      hippocampus and one patient with cavernous angioma were involved in the study.
      Interictal epileptiform activities were classified into two patterns according to
      the topography of spikes. They were widespread spikes over the parasagittal
      electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes
      (temporal spikes). Dipole sources of parasagittal spikes were localized in the
      medio-basal temporal lobe with vertically orientated vector moment. Dipole
      sources of temporal spikes were localized in the medio-basal temporal lobe with
      horizontally orientated vector moment. Locations of dipoles and directions of
      vector moments were consistent with topography and polarity of spikes. The
      difference in the two patterns of interictal epileptiform activities was derived
      from the difference in the direction of the vector moment of dipole sources.
      There was no difference in the location of dipole sources. Both the dipole
      sources and the lesions were localized in the same medio-basal temporal lobe.
      Dipole tracing was very useful in localizing the dipole sources of interictal
      epileptiform activities and in understanding the neurophysiological background.

PMID- 15558876
TI  - Gender differences and reproducibility in exploratory eye movements of normal
      subjects.
AB  - Exploratory eye movements were recorded using an eye-mark recorder in 48 normal
      subjects (24 male and 24 female). Gender differences were examined regarding four
      eye movement parameters such as the mean gazing time, the total number of gazing
      points, and the mean eye scanning length and the total eye scanning length. The
      mean gazing time of women was significantly longer than that of men, and the
      total number of gazing points of women was significantly less than that of men.
      The mean eye-scanning length of men and women did not differ. The total eye
      scanning length of men was significantly longer than that of women.
      Reproducibility between sessions of the four eye movement parameters above was
      expressed as Pearson correlation coefficients (r) in 24 healthy adults before and
      after a month interval, yielding respective coefficients of 0.65, 0.42, 0.56 and
      0.61. These results suggested that differences in exploratory eye movements
      between men and women may reflect differences in the characteristics of visual
      information processing and also confirmed the reproducibility of exploratory eye
      movement parameters.

PMID- 15558877
TI  - Effects of zolpidem and zopiclone on cognitive and attentional function in young
      healthy volunteers: an event-related potential study.
AB  - The effects of zolpidem and zopiclone, non-benzodiazepine ultra-short-acting
      hypnotics, on cognitive function and vigilance level were investigated in the
      morning following nocturnal administration using event-related potentials (ERP)
      and a sleep latency test (SLT). Zopiclone significantly shortened the sleep
      latency the following morning, whereas zolpidem did not, perhaps due to the
      difference in the elimination half-lives between the compounds. No significant
      effect was observed for either drug on the ERP indices, including the P3,
      mismatch negativity and negative difference components. At a clinically
      prescribed dosage these sleep inducers have no remarkable effect on cognitive or
      attentional functions but increase sleepiness of the subjects.

PMID- 15558878
TI  - Seizure recurrence after reduction of an antiepileptic drug in patients with
      unprovoked seizures and severe neurological abnormalities.
AB  - A prospective study of antiepileptic drug (AED) reduction in patients with
      unprovoked seizures and severe neurological abnormalities after a seizure-free
      period of more than 5 years was performed. From a hospital for severely
      handicapped children (150 patients) and an institution for mentally handicapped
      people (89 persons), 13 patients were enrolled to this study after informed
      consent was obtained. All patients had experienced a seizure-free period of more
      than 7 years (median, 10 years). The patients had IQs of less than 50 and were
      almost dependent in their life. Five patients had additional motor deficits. The
      patients had been taking one to three AED (mean, 1.9) before reduction and only
      one AED was withdrawn. During the following 2years, four of the 13 patients (31%)
      showed a recurrence of seizures. The age at the time of the last seizure was
      lower in the seizure-free patients. As to the 10 patients with onset ages of 10
      or less, a significant factor as to seizure recurrence was whether or not
      seizures were controlled before the age of 11 years (P < 0.05, Fisher's exact
      probability test). It is suggested that a patient with severe neurological
      abnormalities, in whom epilepsy or unprovoked seizures are controlled before the
      age of 11 years (i.e. before adolescence) could be a candidate for the reduction
      of AED.

PMID- 15558879
TI  - Distribution of amyloid beta protein precursor in the Alzheimer's disease brain.
AB  - In order to clarify the distribution and pathological changes of the amyloid beta
      protein precursor (betaAPP), 10 Alzheimer's disease (AD) brains and seven normal
      control brains were examined by immunocytochemistry and in situ hybridization
      histochemistry. All betaAPP isoforms were distributed evenly in neuronal cell
      bodies and their axons and dendrites. The betaAPP-positive neuronal processes
      showed mesh-like networks. In AD brains, betaAPP-positive neurons and mesh-like
      networks were generally decreased in spite of some intensely labeled neurons. All
      betaAPP isoforms accumulated in neuronal processes, dystrophic neurites and
      senile plaques. In situ hybridization histochemistry confirmed that all isoforms
      of betaAPP were expressed in neurons in control brains. In AD brains, the betaAPP
      mRNA signal was generally decreased besides some intense signal neurons
      corresponding to immunostaining findings. Few astrocytes expressed betaAPP. Thus,
      uniform expression and distribution of betaAPP were disturbed in AD brains
      showing uneven decreases or increases of neuronal betaAPP expression in
      individual neurons and betaAPP accumulation in neurons, neuronal processes and
      abnormal structures including dystrophic neurites, senile plaques and
      neurofibrillary tangles.

PMID- 15558880
TI  - Application of telepsychiatry: a preliminary study.
AB  - Telemedicine is the provision of professional medical services from sites removed
      from the patient. This study was conducted in order to assess the reliability of
      psychiatric evaluations via video-consultation. The inter-rater reliability was
      determined for each interviewing condition by employing the reliability-testing
      paradigm in which the brief psychiatric rating scale (BPRS) and the interclass
      correlation coefficient (ICC) are used. The inter-rater reliability scores
      between face-to-face interviews and interviews conducted by video at two
      different levels of image qualities were compared by the authors. Reliability was
      found to be in perfect agreement in each of the interviewing conditions. This
      study verifies that telepsychiatry is a reliable method of assessing patient
      conditions. It may be used to provide much needed mental health-care services to
      patients whose access to them is restricted.

PMID- 15558881
TI  - Mood disorders and influenza epidemics in Japan.
AB  - The finding that influenza epidemics are associated with an increased risk of
      adult mood disorder has been controversial. In this study, data were collected
      from governmental statistics, the Patient Survey in Japan, in 1996. Index years
      were defined as 1957/58, 1962, and 1965, and comparison years were defined as 2
      years before and 2 years after the index year. The subjects were 361 patients
      with mood disorders who were born in the index years of influenza epidemics. In
      order to isolate patients exposed to an influenza epidemic during their second
      prenatal trimester, the months of birth 5 months after the influenza epidemics
      were defined as risk exposure months. The proportions of patients born during the
      exposure period in the index years were compared with those of patients born in
      the corresponding months in the comparison years. The same procedures were
      conducted for the periods 2 and 8 months after the epidemics. For female
      inpatients only, the proportion of patients born in the A2 influenza-exposure
      months in 1965 with second-trimester exposure was smaller than that of patients
      born in the corresponding months in the comparison years; the same phenomenon was
      observed for third-trimester exposure in 1957-58. However, no differences were
      observed in other comparisons. These findings suggest that prenatal exposure to
      influenza might decrease the risk for adult mood disorders in females. However,
      whether there is a causal relationship is still unproven.

PMID- 15558882
TI  - An empirical classification of social anxiety: performance, interpersonal and
      offensive.
AB  - This study empirically identified subtypes of social anxiety using a cluster
      analytic approach. From 87 out-patients with social phobia (taijin kyofusho) and
      48 controls, social anxiety symptoms, social situations in which symptoms occur,
      and background information were evaluated. Factor analysis using the ratings of
      social anxiety symptoms identified four factors: socially inadequate feelings,
      performance anxiety, offensive fear, and tenacity. Four subtypes emerged from
      cluster analysis based on the factor scores and they were called performance
      anxiety type, offensive type, interpersonal anxiety type and mild type. Chi2 test
      and analysis of variance revealed the following: (i) the offensive type had the
      greatest symptom severity. Any situation could provoke symptoms, and
      interpersonal tense feelings became much stronger with persons of the same age;
      (ii) the interpersonal anxiety type was characterized by the fear of social
      interaction in daily life; and (iii) patients with the offensive type and the
      interpersonal anxiety type presented more difficulties than did those with the
      performance anxiety type on developmental and premorbid adjustment.

PMID- 15558883
TI  - Effects of gender difference and birth order on perceived parenting styles,
      measured by the EMBU scale, in Japanese two-sibling subjects.
AB  - The relationship between Egna Minnen av Barndoms Uppforstran (EMBU) scaling and
      gender, birth order and parents' gender was previously investigated in a large
      volunteer sample; significant interactions among the variables were found. In the
      present study, 730 Japanese volunteers with one sibling were used as subjects in
      order to control the number of siblings: the effect of gender of subjects and
      siblings and birth order on the perceived parenting style was examined. Based on
      gender and birth orders, 730 subjects were grouped into the following categories:
      (i) male with a younger brother; (ii) male with a younger sister; (iii) male with
      an older brother; (iv) male with an older sister; (v) female with a younger
      brother; (vi) female with a younger sister; (vii) female with an older brother;
      and (viii) female with an older sister. One-way ANOVA was performed with each
      EMBU subscale used as a dependent variable and these eight groups as independent
      variables. The scores for rejection and emotional warmth of father were
      influenced significantly by the pattern of siblings (P<0.006 and P<0.0012,
      respectively), and scores for emotional warmth of mother were influenced
      significantly by the pattern of siblings (P<0.0012). The elder male children
      strongly experienced parenting style as more rejecting than others, and female
      children (elder sisters with brother, or younger sisters with sister) recognized
      parenting style as more caring and demonstrated more warmth than others. The
      results confirmed a significant interaction of gender of subjects and siblings
      and birth order of perceived parental rearing behavior.

PMID- 15558884
TI  - Changes in limbic dopamine metabolism following quinolinic acid lesions of the
      left entorhinal cortex in rats.
AB  - To examine the effects of lesions of the entorhinal cortex on limbic dopamine
      (DA) metabolism, DA and its metabolites were assayed in five brain regions (the
      medial prefrontal cortex, anterior cingulate cortex, caudate-putamen, accumbens
      nucleus, and lateral amygdala), 14 and 28 days after quinolinic acid or sham
      lesions of the left entorhinal cortex in rats. Concentrations of 3,4
      dihydroxyphenylacetic acid (DOPAC) on day 14 in the medial prefrontal cortex,
      accumbens nucleus, and lateral amygdala of the entorhinal cortex lesioned animals
      were significantly decreased compared with the controls, but they returned to
      control levels on day 28. The concentration of DA in the lateral amygdala and
      spontaneous locomotion to a novel environment were significantly increased on day
      28 after the lesion. These results suggest that entorhinal cortex lesions alter
      mesolimbic dopamine metabolism, particularly in the amygdala.

PMID- 15558885
TI  - The influences of family environment on personality traits.
AB  - In order to clarify the influences of family environment on the development of
      personality traits, 150 children (104 males and 46 females, mean age 13.2 +/- 2.4
      years) who had been interviewed at the Child Guidance Clinic in Osaka were
      investigated. From 13 behavioral characteristics (activity, talkativeness,
      sociability, social skills, rule-keeping, will, aggression, emotional control,
      imagination, anxiety, maturity, intelligence, and neuroticism), factor analysis
      identified three personality traits: extraversion, maturity, and intellect. The
      effects of family environment (maternal and paternal participation in child
      rearing before and after 4years of age, child-rearing style, parental
      relationship, sibling relationship, number of siblings, birth order, and
      socioeconomic status) on these personality traits were examined based on a
      structural equation model. The results found, first, that extraversion was
      negatively associated with overprotection/interference and with maternal
      participation in child rearing. Maturity correlated with high socioeconomic
      status, appropriate child-rearing style, and paternal participation in child
      rearing. Intellect was related to high socioeconomic status and maternal
      participation in child rearing. Second, path analysis with selected variables
      revealed that 8% of variance in extraversion, 14% in maturity, and 10% in
      intellect was due to family environment. Third, children with high introversion
      or high intellect had stronger influences from family environment than did those
      with high extraversion or low intellect.

PMID- 15558886
TI  - Psychological effect of the Nagasaki atomic bombing on survivors after half a
      century.
AB  - In 1997 a mental health survey using a 30-item General Health Questionnaire (GHQ
      30) and an interview survey of an atomic bombing experience were conducted in
      survivors of the Nagasaki atomic bombing. Overall psychological distress measured
      on the basis of the GHQ-30 was greater in the atomic bombing survivors than in
      the controls. As for the contents of psychological distress, those concerning
      emotion such as anxiety and depression were milder in survivors than in the
      controls, but those related to social activities such as apathy, disturbance of
      human relations, loss of enjoyment of living were more severe. Furthermore,
      recurring and distressing recollection of the experience of the atomic bombing,
      suspicion over the relationship between the atomic bombing and an unhealthy
      physical condition, and the experience of witnessing death or severe injury of
      close relatives due to the atomic bombing were significantly related to the
      degree of psychological distress of the survivors.

PMID- 15558887
TI  - Hippocampus and amygdala volumes in elderly schizophrenic patients as assessed by
      magnetic resonance imaging.
AB  - Reduced size of the hippocampus and amygdala has been one of the more consistent
      morphological findings in schizophrenia, but the question of medial temporal
      abnormalities in elderly schizophrenia patients has been inadequately addressed.
      We examined 20 elderly subjects with a DSM-III-R diagnosis of schizophrenia, five
      of whom had a late-onset schizophrenia (LOS), and compared them with 20 healthy
      volunteers on magnetic resonance imaging (MRI) and neuropsychological parameters.
      Hippocampus and amygdala volumes were obtained by manual tracing on T1-weighted
      1.5 mm thick contiguous coronal slices perpendicular to the long axis of the
      hippocampus. Patients had smaller left hippocampal and right amygdala volumes
      than comparison subjects, the mean differences being 9.7 and 11.1%, respectively,
      but the right amygdala volumes were not significantly different after Bonferroni
      correction. The hippocampus-amygdala volumes together were smaller in the
      schizophrenia group bilaterally. In a pilot analysis, the LOS subjects had non
      significantly smaller hippocampus-amygdala volumes than did the early-onset
      schizophrenia (EOS) subjects. For the schizophrenia group, there were significant
      correlations between amygdala and hippocampus volumes and some neuropsychological
      performance indices. The findings are consistent with those reported in younger
      schizophrenics, and are of the same order of magnitude, suggesting that they are
      not likely to be progressive. This pilot analysis in LOS subjects argues against
      the condition being secondary to Alzheimer's disease.

PMID- 15558888
TI  - Myotonic dystrophy associated with 47 XYY syndrome.
AB  - A case of myotonic dystrophy with 47 XYY presented with tall stature and mental
      retardation. The patient was a 37-year-old male. In addition to grip myotonia and
      percussion myotonia, severe weakness and atrophy were noted in the face and the
      neck muscles and in the distal muscles of the four limbs. He also had diabetes
      mellitus, cataracts and sexual behavior abnormalities. He was found to be 47 XYY
      from chromosomal examinations. The combination of 47 XYY syndrome and myotonic
      dystrophy has not been reported previously.

PMID- 15558889
TI  - White matter hyperintensity detected by magnetic resonance imaging and lithium
      response in bipolar disorder: a preliminary observation.
AB  - The possible relationship between deep white matter hyperintensity (WMHI) lesions
      detected by magnetic resonance imaging and response to lithium was examined in 16
      patients with bipolar disorder who had been under maintenance treatment with
      lithium for more than 1 year. Bipolar patients who had higher scores of WMHI
      responded significantly better to lithium (r = 0.57, P < 0.05) than did those who
      had lower scores. This preliminary result suggests that the presence of WMHI may
      be associated with a better response to lithium.

PMID- 15558890
TI  - [Security risks increase costs].

PMID- 15558891
TI  - [Economizing makes patients and nurses sick].

PMID- 15558892
TI  - [Assuming responsibility].

PMID- 15558893
TI  - [Old age as a complex generation theme].

PMID- 15558895
TI  - [Your fantasy is required].

PMID- 15558894
TI  - ["Taking credit for the health market"].

PMID- 15558896
TI  - ["We must go to the people"].

PMID- 15558897
TI  - [Finding the way from "I must" to "I can"].

PMID- 15558898
TI  - [When caring involves "costs"].

PMID- 15558899
TI  - [Good to know: night economizing].

PMID- 15558900
TI  - [Patients come up against maltreatment].

PMID- 15558901
TI  - [Constraint: between necessity and abuse].

PMID- 15558902
TI  - [Two principles and and eight compliments].

PMID- 15558903
TI  - [Deeds prove imagination!].

PMID- 15558904
TI  - [Lessening security increases costs].

PMID- 15558905
TI  - [Injury prevention in health].

PMID- 15558906
TI  - [Show proof of you fantasies].

PMID- 15558907
TI  - ["I can, but I don't want to"].

PMID- 15558908
TI  - CMS and JCAHO quality measures now are the same: will that save you time?

PMID- 15558909
TI  - Try creative strategies for do-not-use abbreviations.

PMID- 15558910
TI  - Survey finds problems with nonurgent medications.

PMID- 15558911
TI  - Incident evaluations aid voluntary reporting.

PMID- 15558912
TI  - Stroke in atrial fibrillation: a need for effective anticoagulation.

PMID- 15558913
TI  - Thoracoscopic approach to delayed hemopericardium.

PMID- 15558914
TI  - A stitch in time: predicting long-term survival after acute gastrointestinal
      hemorrhage.

PMID- 15558915
TI  - Clinical correlation between effective anticoagulants and risk of stroke: are we
      using evidence-based strategies?
AB  - OBJECTIVES: Despite evidence supporting anticoagulant use in atrial fibrillation,
      this modality is not fully utilized. METHODS: Retrospective chart review of 297
      patients with nonvalvular atrial fibrillation between 1997 to 2000. 124 patients
      received warfarin and 166 did not; 91 patients suffered stroke. RESULTS: Age (P =
      0.232) and gender (P = 0.745) were not determinant factors for starting
      anticoagulation prophylaxis. Whites were more likely to receive anticoagulation
      therapy than blacks (P = 0.043). Cardiologists were 4.5 times more likely to
      prescribe warfarin than neurologists and internists (P = 0.035). Neurologists (P
      = 0.305) and internists (P = 0.770) had similar warfarin prescription patterns
      and often with patients experiencing the highest rates of stroke. CONCLUSION:
      Lack of a uniform pattern in anticoagulant administration, despite multiple
      guidelines, is disturbing. Continuous physician education and community awareness
      by local and federal medical agencies is essential and cost-effective.

PMID- 15558916
TI  - A systematic approach to managing hypertension and the metabolic syndrome in
      primary care.
AB  - OBJECTIVES: Obesity is driving a high prevalence of hypertension and metabolic
      syndrome-related risk and disease. This report summarizes the impact of a
      standardized, evidence-based approach to managing high blood pressure and
      associated metabolic syndrome abnormalities that was developed and implemented by
      one Clinical Hypertension Specialist. METHODS: Longitudinal data on blood
      pressure, low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c),
      cardiovascular and renal comorbidities, and treatment medications were obtained
      on all 817 hypertensive patients seen from January 1, 2000 to June 30, 2003.
      RESULTS: The hypertensive patients were 72 +/- 11 (SD) years old, and more than
      55% of them were high risk based on target organ damage, clinical cardiovascular
      disease, or diabetes mellitus. Blood pressure was < 140/90 mm Hg in 77% of all
      patients. Among the high-risk patients, mean blood pressure was 126 +/- 14/71 +/-
      10 on 2.8 +/- 1.4 antihypertensive medications, with 88% on angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers, 59% on diuretics,
      49% on calcium channel blockers, and 36% on beta-blockers. Among dyslipidemic
      hypertensives, LDL-C was controlled to < 130 mg/dL in 84% (510/605) overall and
      to < 100 mg/dL in 70% of the high-risk group (299/427). Among diabetic
      hypertensives, the mean HbA1c was 6.8%, with 64% (155/242) less than 7%. New
      patients demonstrated improved blood pressure, LDL-C, and hemoglobin A1c control
      over time as the management algorithm was applied. CONCLUSIONS: A high prevalence
      of complicated hypertension was documented. Blood pressure, LDL-C, and HbA1c were
      controlled to goal in a high proportion of patients. The findings demonstrate
      that application of an evidence-based management algorithm can facilitate higher
      rates of cardiovascular risk factor control than are generally reported in
      primary care practices.

PMID- 15558917
TI  - Brachial blood pressure monitoring versus ankle monitoring during colonoscopy.
AB  - OBJECTIVES: To compare ankle and brachial blood pressure monitoring before and
      during colonoscopy using automated noninvasive blood pressure (NIBP) monitors.
      METHODS: Forty-five consecutive patients who presented for outpatient colonoscopy
      had both ankle and brachial blood pressure monitoring with automated NIBP using
      an appropriately sized cuff for arm or leg size. Three baseline measurements were
      obtained, and then measurements were taken at 5-minute intervals during conscious
      sedation, with brachial blood pressure being the standard. RESULTS: The average
      of all of the ankle blood pressures was significantly higher for all systolic and
      mean arterial blood pressure readings. Diastolic blood pressure readings were
      higher at baseline, but not significantly different during the procedure.
      CONCLUSIONS: Ankle systolic and mean arterial blood pressures using automated
      NIBP monitoring for conscious sedation are significantly higher than brachial
      blood pressures. Ankle NIBP monitoring should only be used if brachial NIBP
      monitoring is not feasible, taking into consideration that ankle NIBP pressures
      are generally higher than brachial.

PMID- 15558918
TI  - Measuring provider compliance with ischemic heart disease guidelines.
AB  - OBJECTIVES: The purpose of this study was to assess the relationships among
      provider beliefs, attitudes, and intention to use Veterans Health Administration
      guidelines for ischemic heart disease (IHD). METHODS: A self-administered written
      questionnaire was mailed to providers at six Veterans Administration hospitals in
      a Veterans Integrated Service Network. The questionnaire measured the providers'
      general impression of the IHD guidelines, factors that influence use of cardiac
      medications, and barriers to using the guidelines. RESULTS: A total of 170 of 491
      eligible providers returned the questionnaire (35% response rate). The top
      reasons cited for following the guidelines were to decrease mortality, prevent
      future myocardial infarction, decrease the risk of recurrent events, and provide
      positive cardiac effects. The authors found that, overall, providers have a
      positive impression of the IHD guidelines because they provide a standard of care
      and result in higher quality of care. CONCLUSIONS: The authors' results indicate
      that providers support the guidelines, but encounter barriers in accessing them.

PMID- 15558919
TI  - Erythema marginatum and hereditary angioedema.
AB  - OBJECTIVE: To search for anaphylatoxin activity in plasma during episodes of
      erythema marginatum, and to evaluate the histology of erythema marginatum by
      electron microscopy and immunohistologic techniques. METHODS: Plasma samples were
      studied for C5a activity by granulocyte aggregation, and C3 conversion by
      immunoelectrophoresis. A skin biopsy of erythema marginatum was done, and the
      tissue stained with a rabbit antibody to bradykinin. RESULTS: No plasma
      anaphylatoxin was found. Dense deposits of bradykinin were discovered in stromal
      tissue and lining endothelial cells. CONCLUSIONS: Bradykinin may be important in
      the causality of the erythema marginatum associated with hereditary angioedema.

PMID- 15558920
TI  - Predictive power of cardiovascular risk factors for detecting peripheral vascular
      disease.
AB  - OBJECTIVES: Peripheral vascular disease (PVD) is underdiagnosed in primary care
      due to the absence of established criteria to warrant diagnostic testing. Our
      goal was to establish a risk factor hierarchy to enable earlier diagnosis of PVD.
      METHODS: Data sets of 142 patients with abnormal ankle brachial indices (ABI)
      were randomly selected from our patient database to determine the prevalence of
      specific cardiovascular risk factors and demographic data. An ABI score < 0.90 is
      diagnostic of PVD. Patients were stratified into mild (0.75-0.89), moderate (0.50
      0.74), and severe disease (< 0.50). RESULTS: Mean age was 69 +/- 9.9, ABI 0.65 +/
      0.16. Risk factor prevalence: diabetes, 42%; hypertension, 87%; tobacco use,
      34%; hyperlipidemia, 53%; obesity, 24%; cardiovascular disease (CVD), 69%;
      stroke, 15%. Total risk factors per patient v = 3.2 +/- 1.3. Disease severity
      stratifications: mild, n = 46 (age v = 68.6 +/- 10.4, ABI v = 0.82 +/- 0.05);
      moderate, n = 72 (age v = 69.9 +/- 9.4, ABI v = 0.62 +/- 0.07); severe, n = 24
      (age v = 67.5 +/- 10.9, ABI v = 0.40 +/- 0.06). Independent variable mean
      differences: hypertension-CVD (P = 0.0002); CVD-hyperlipidemia (P = 0.002);
      hyperlipidemia-diabetes (P = 0.0008); diabetes-tobacco use (P = 0.001); tobacco
      use-obesity (P = 0.0003); obesity-stroke (P = 0.05). Independent variable mean
      differences were significant across disease severity (P < 0.00001). CONCLUSIONS:
      Our study establishes the following hierarchy of cardiovascular risk factors as
      predictors of PVD: hypertension, cardiovascular disease, hyperlipidemia,
      diabetes, tobacco use, obesity, stroke.

PMID- 15558921
TI  - Long-term mortality of patients admitted to the intensive care unit for
      gastrointestinal bleeding.
AB  - OBJECTIVES: Long-term mortality data for gastrointestinal (GI) bleeders is scarce
      in the literature. The aim of this prospective study was to determine the long
      term mortality of patients admitted to two intensive care units with a primary
      diagnosis of GI bleeding. METHODS: The charts of patients admitted to the medical
      intensive care unit (MICU) with GI bleeding were reviewed and the data of the
      patients' first day in the MICU was used to calculate APACHE III and Charlson
      scores. A GI bleeding score was computed by combining endoscopic findings and
      units of blood transfused during patients' MICU stay. Mortality data was obtained
      from the Vital Statistics Department of Montgomery County, Dayton, OH. Survival
      data and predictability of mortality based on these scores were assessed.
      RESULTS: Mean age of the 66 patient cohort was 58.6 years. Twenty-six of 51
      patients with upper GI bleeding, five of seven patients with lower GI bleeding,
      and four of eight patients with unknown site of bleeding died within 7 years.
      Charlson score correlated significantly with the mortality prediction, whereas
      the APACHE III and bleeding scores did not. CONCLUSIONS: All-cause and GI
      bleeding-related 7-year mortality for patients admitted to the MICU with GI
      bleeding was lower than the rates cited in the literature. The Charlson score was
      helpful in predicting mortality.

PMID- 15558922
TI  - Leukemoid reactions complicating colitis due to Clostridium difficile.
AB  - BACKGROUND: We sought to describe the characteristics of patients who had
      Clostridium difficile colitis complicated by leukemoid reactions (total leukocyte
      count greater than 35 x 10(9)/L) and to determine whether this complication is
      associated with higher morbidity or mortality than C difficile colitis without
      leukemoid reactions. METHODS: We performed a retrospective case series analysis
      of patients with a positive fecal assay for C difficile toxin and a peak
      leukocyte count greater than 35 x 10(9)/L during 1998 and 1999. Twenty cases that
      met these criteria were compared with 65 randomly selected control patients
      (patients with a positive C difficile toxin and a peak leukocyte count less than
      35 x 10(9)/L). RESULTS: The mean peak leukocyte count was 52 +/- 18.2 x 10(9)/L
      (+/- SD) in the case group and 14.9 +/- 6.5 x 10(9)/L in the control group.
      Patients with a leukemoid reaction had a lower temperature, a lower serum albumin
      level, and a higher hematocrit value. Multivariable logistic regression showed
      respiratory tract infection and lower temperature to be independent predictors of
      a leukemoid reaction. There were 10 deaths (50%) in the leukemoid reaction group
      and 5 deaths (7.7%) in the control group. All seven patients with a peak
      leukocyte count greater than 50 x 10(9)/L died, compared with eight deaths
      (10.3%) among the remaining 78 patients whose peak leukocyte count was less than
      50 X 10(9)/L. CONCLUSION: Patients with C difficile colitis and a leukocyte count
      greater than 35 x 10(9)/L have a poor prognosis with a much higher mortality rate
      than patients who have C difficile colitis without a leukemoid reaction.

PMID- 15558923
TI  - Pregnant adolescents' preferences for labor pain management.
AB  - OBJECTIVES: The purpose of this study was to examine the obstetric anesthesia
      method used, based on the patient's age. Confounding variables analyzed were the
      effect on labor pain management choices of parity, race, prenatal care
      participation, insurance status, and length of labor. METHODS: This was a case
      control study from the Medical University of South Carolina (MUSC). The primary
      outcome measured was regional anesthesia (RA) use in labor. The exposure groups
      were based on the patient's age. All women aged 11 years and older who delivered
      vaginally from 1996 to 2001 were included; 7,583 patients met inclusion criteria.
      Results were analyzed using chi2 statistic, univariate analysis, ANOVA, and
      logistic regression. RESULTS: We found that primiparous adolescents used RA less
      than primiparous women over age 20. This association is not found in multiparous
      teens. Patients with shorter labors, black women, those without prenatal care,
      and older patients lacking private insurance declined RA more often. CONCLUSIONS:
      RA is the most utilized form of obstetric pain management in the last decade. In
      primiparous adolescents, declining RA cannot be explained by length of labor,
      race, insurance status, or prenatal care participation.

PMID- 15558924
TI  - Proteinuria and microalbuminuria in adults: significance, evaluation, and
      treatment.
AB  - This paper reviews current concepts regarding the pathophysiology, diagnostic
      evaluation, and treatment of microalbuminuria and proteinuria in adults.
      Microalbuminuria (in diabetics) and proteinuria are early markers for potentially
      serious renal disease, and are associated with increased risk of atherosclerotic
      cardiovascular disease. Proteinuria also contributes to renal scarring, and
      accelerates the progression of chronic kidney disease to end-stage renal failure.
      Screening of diabetics for microalbuminuria, and the initial workup of
      proteinuria, should occur in the primary care setting. Reduction of
      microalbuminuria in diabetics may retard its progression to overt diabetic
      nephropathy. Therapy of renal diseases should aim for optimal blood pressure
      control and the maximum possible reduction in urinary protein excretion.
      Angiotensin-converting enzyme inhibitor (ACE-I) and/or angiotensin-receptor
      blocker (ARB) therapy is the most effective measure to achieve this. These drugs
      also provide protection against the cardiovascular problems that are highly
      prevalent in this patient population.

PMID- 15558925
TI  - Pheochromocytoma and myocardial infarction.
AB  - Pheochromocytomas are rare chromaffin cell tumors, 90% of which arise from the
      adrenal glands. Pheochromocytomas presenting with true myocardial infarction are
      even more rare. We report a 76-year-old man who had a previously undiagnosed
      pheochromocytoma, and presented with the uncommon complication of myocardial
      infarction. Our high-risk patient was managed with the combination of
      simultaneous coronary artery bypass grafting and adrenalectomy.

PMID- 15558926
TI  - Clinical use of C-reactive protein for cardiovascular disease.
AB  - Recent evidence supports an association between elevation of inflammatory
      markers, such as C-reactive protein, and subsequent cardiovascular disease risk.
      The American Heart Association released guidelines in 2003 to help clinicians
      know when to use such markers. Because inflammatory markers are associated with
      diabetes, obesity, and hypertension, knowledge of the role of such markers is
      extremely important for prevention and chronic disease management. Newer studies
      published after the guidelines, and another recent review provide further
      documentation of the growing role of inflammation in cardiovascular risk. Based
      on the available literature, this article reviews the new guidelines, more recent
      evidence since the guidelines, and forms recommendations for primary care
      clinical practice.

PMID- 15558927
TI  - Skin toxicity during breast irradiation: pathophysiology and management.
AB  - Radiotherapy is a critical component in the treatment of breast cancer, a disease
      that is estimated to have affected 203,500 US women in 2002. According to the
      data from some series, an estimated 90% of patients treated with radiotherapy for
      breast cancer will develop a degree of radiation-induced dermatitis. This review
      describes the indications and techniques of radiotherapy for breast cancer. The
      pathophysiology, clinical presentation, and contributing factors of radiation
      related skin injury are discussed. A review of recent clinical research
      addressing skin toxicity is provided.

PMID- 15558928
TI  - Delayed hemopericardium after penetrating chest trauma: thoracoscopic pericardial
      window as a therapeutic option.
AB  - A 41-year-old male developed a hemothorax after sustaining a stab wound in the
      right chest. The patient was managed conservatively with thoracostomy tube
      drainage for 3 days and was subsequently discharged home. Two weeks later the
      patient returned to the hospital with pleuritic chest pain and shortness of
      breath. Imaging studies revealed a right-sided pleural effusion and an enlarged
      cardiac silhouette, which was consistent with pericardial effusion as per
      ultrasonography. Thoracoscopic exploration revealed an enlarged heart, that
      following pericardiotomy drained 400 mL of frank blood. Subsequently, cardiac
      contractility improved, and no further bleeding was evident.

PMID- 15558929
TI  - Peduncular hallucinosis: unusual complication of cardiac catheterization.
AB  - Peduncular hallucinosis (PH) is a rare form of visual hallucination characterized
      by vivid, nonstereotypical visual images of people, animals, and plants of brief
      duration that are nonthreatening to the patient. The clinical syndrome of PH
      consists of formed visual hallucinations, localizing signs of the offending
      lesion, and sleep disturbances. In the absence of localizing focal neurologic
      deficits, it is easily confused with a delirium or psychosis. It is seen with
      lesions involving the upper brainstem and diencephalon. The authors report a case
      of PH due to ischemic infarction of the midbrain after cardiac catheterization.
      Although PH has been reported after vertebral angiography, it has never been
      reported as a complication of cardiac catheterization.

PMID- 15558930
TI  - A case of congestive heart failure due to reversible dilated cardiomyopathy
      caused by hyperthyroidism.
AB  - Thyrotoxicosis is an uncommon cause of low-output congestive heart failure. The
      case of a 41-year-old male who presented with severe symptomatic congestive heart
      failure, and was subsequently diagnosed with dilated cardiomyopathy secondary to
      hyperthyroidism, is presented. The cause of his hyperthyroidism was Graves
      disease. Despite an initial left ventricular systolic ejection fraction of 20%
      and evidence of global hypokinesis on echocardiography, treatment with
      antithyroid agents led to rapid improvement in his clinical status and
      normalization of his ejection fraction. The proposed mechanisms underlying the
      development of systolic dysfunction in thyrotoxicosis are discussed, and the
      literature on similar cases previously reported is reviewed.

PMID- 15558931
TI  - Evolving infectious aortitis caused by Streptococcus pneumoniae.
AB  - Infections of major vessels leading to mycotic aneurysms can be a diagnostic
      dilemma for clinicians, and can be accompanied by a high mortality rate.
      Successful treatment of this condition often requires a high index of suspicion
      and prompt medical and surgical attention. The authors report two cases of
      infectious aortitis caused by pneumococcus that evolved during hospitalization,
      and discuss diagnostic difficulties that accompany this entity.

PMID- 15558932
TI  - Fulminant myocarditis presenting with wide complex tachycardia.
AB  - Fulminant myocarditis is an uncommon diagnosis characterized by cardiac failure
      preceded by symptoms of a viral illness. Presentation can frequently mimic acute
      myocardial infarction. The electrocardiographic changes are frequently
      nonspecific, but include ST segment elevation and T wave changes, as well as
      conduction abnormalities. We report the case of a patient with fulminant
      myocarditis that presented with sinus rhythm, a conduction system abnormality,
      and severe ST segment elevation mimicking ventricular tachycardia. Myocarditis
      should be considered in young persons with unexplained heart failure and similar
      electrocardiographic abnormalities.

PMID- 15558933
TI  - 20-year follow-up of a patient with coronary artery spasm.
AB  - The authors present a 20-year follow-up of a patient with well-documented
      coronary artery spasm, who initially presented with syncope. The patient had
      excellent response to calcium channel antagonists and long-acting nitrates.

PMID- 15558934
TI  - Elevation of the tumor marker CA125 in right heart failure.
AB  - Carbohydrate antigen 125, known as a marker for ovarian cancer, has been reported
      to be elevated in heart failure caused by left ventricular dysfunction. A case of
      elevated carbohydrate antigen 125 in isolated right heart failure due to atrial
      septal defect with preserved left ventricular function is reported.

PMID- 15558935
TI  - Tenecteplase and return of spontaneous circulation after refractory
      cardiopulmonary arrest.
AB  - Even with the benefit of cardiopulmonary resuscitation, the prognosis of cardiac
      arrest remains poor. Multiple case series describe survival with the use of
      thrombolytic therapy for refractory cardiac arrest. Presumably thrombolysis
      treats that subset of cardiac arrest cases resulting from fulminant pulmonary
      embolism, or perhaps massive myocardial infarctions. Published reports to date
      have dealt exclusively with streptokinase, urokinase, reteplase, or recombinant
      tissue plasminogen activator. The authors report the first case of return of
      spontaneous circulation with the administration of tenecteplase. Tenecteplase is
      a recently developed reengineered isomer of tissue plasminogen activator that
      possesses many properties of the ideal cardiac arrest thrombolytic agent. It is
      bolus dosed, stable at room temperature before reconstitution, and is compatible
      with most other advanced cardiac life support medications. Because of clinical
      equivalency and its logistical advantages, tenecteplase should be evaluated as an
      alternative to other thrombolytics in future trials involving cardiac arrest.

PMID- 15558936
TI  - Prosthetic valve endocarditis presenting as loss of the metallic click sound.
AB  - Prosthetic valve endocarditis is a significant infection. It is often serious,
      and may result in a complicated course leading to valvular malfunction. We
      present the case of a 50-year-old male with an aortic Medtronic Hall valve, who
      presented with loss of his normal metallic click. A transthoracic echocardiogram
      confirmed the diagnosis of endocarditis and of an aortic-root abscess. Blood
      cultures were positive for nutritionally deficient Streptococcus. He underwent
      successful surgery and later was discharged. Patients with mechanical heart
      valves are often bothered by the metallic sound. It can interfere with their
      daily life. However, the loss of the click may indicate valvular dysfunction,
      dehiscence of the prosthesis, and/or tissue infection with abscess formation.

PMID- 15558937
TI  - Endometriosis of the pancreas presenting as a cystic pancreatic neoplasm with
      possible metastasis.
AB  - The authors report a case of endometriosis that presented as a cystic mass in the
      tail of the pancreas, leading to extensive evaluation and ultimately a major
      surgical resection. The diagnosis was made by histopathological evaluation,
      revealing endometrial glands and stroma in the wall of the mass with hemorrhagic
      fluid in the cystic lumen, compatible with pancreatic involvement by an
      endometrial cyst.

PMID- 15558938
TI  - Apolipoprotein epsilon4 homozygosity and essential hypertension.

PMID- 15558939
TI  - Infective endocarditis due to Providenca stuartii.

PMID- 15558940
TI  - Antenatal diagnosis of an extrahepatic portal vein aneurysm.

PMID- 15558941
TI  - Problems with subjective in-training evaluations.

PMID- 15558942
TI  - Dermatitis artefacta in a patient with recurrent larynx cancer: a rare self
      inflicted dermatosis.

PMID- 15558943
TI  - The patient's page. Radiation and skin toxicity.

PMID- 15558944
TI  - Synthesis of cyclopropane isosteres of the antiepilepsy drug vigabatrin and
      evaluation of their inhibition of GABA aminotransferase.
AB  - The antiepilepsy drug vigabatrin (1; 4-aminohex-5-enoic acid; gamma-vinyl GABA)
      is a mechanism-based inactivator of the pyridoxal 5'-phosphate (PLP)-dependent
      enzyme gamma-aminobutyric acid aminotransferase (GABA-AT). Inactivation has been
      shown to proceed by two divergent mechanisms (Nanavati, S. M. and Silverman, R.
      B. (1991) J. Am. Chem. Soc. 113, 9341-9349), a Michael addition pathway (Scheme
      2, pathway a) and an enamine pathway (Scheme 2, pathway b). Analogs of vigabatrin
      with a cyclopropyl or cyanocyclopropyl functionality in place of the vinyl group
      (2-5) were synthesized as potential inactivators of GABA-AT that can inactivate
      the enzyme only through a Michael addition pathway, but they were found to be
      only weak inhibitors of the enzyme.

PMID- 15558945
TI  - Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.
AB  - A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related
      semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine
      whether the relative locations of aryl rings and amidic groups would lead to
      novel anticonvulsant agents. Initially the compounds were administered
      intraperitoneally to mice and examined in the maximal electroshock (MES),
      subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The
      biodata revealed that anticonvulsant properties were displayed by most of the
      compounds in series (1), in half of the semicarbazones (2) while protection was
      absent by members of series (3). Molecular modeling was utilized in order to
      compare the positions of a phenyl ring in relation to amidic groups in
      representative compounds in series (1-3) with previously reported anticonvulsant
      agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la)
      led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with
      retention of anticonvulsant properties. Both (la) and (8) afforded protection in
      the hippocampal kindling screen in rats. When administered orally to rats, (la)
      and (8) demonstrated activity in the MES screen and in the case of (8), a huge
      protection index was observed revealing it to be an important lead compound. The
      IC50 values of all of the compounds towards murine P388 cells were in excess of
      50 microM while several compounds displayed cytotoxicity towards Mycobacterium
      tuberculosis.

PMID- 15558946
TI  - Inhibitory activity of cyanidin-3-rutinoside on alpha-glucosidase.
AB  - Cyanidin-3-rutinoside, a natural anthocyanin, inhibited alpha-glucosidase from
      baker's yeast in dose-responsive manner. The IC50 value was 19.7 microM +/- 0.24
      microM, compared with the IC50 value of voglibose (IC50 = 23.4 +/- 0.30 microM).
      Cyanidin-3-rutinoside was found to be a non-competitive inhibitor for yeast alpha
      glucosidase with a Ki value in the range of 1.31-1.56 x 10(-5)M. These results
      indicated that cyanidin-3-rutinoside could be classed as a new alpha-glucosidase
      inhibitor.

PMID- 15558947
TI  - The effect of cations on the amidase activity of human tissue kallikrein: 1
      linear competitive inhibition by sodium, potassium, calcium and magnesium. 2
      linear mixed inhibition by aluminium.
AB  - Hydrolysis of D-valyl-L-leucyl-L-arginine p-nitroanilide by human tissue
      kallikrein (hK1) was studied in the absence and in the presence of increasing
      concentrations of the following chloride salts: sodium, potassium, calcium,
      magnesium and aluminium. The data indicate that the inhibition of hK1 by sodium,
      potassium, calcium and magnesium is linear competitive and that divalent cations
      are more potent inhibitors of hK1 than univalent cations. However the inhibition
      of hK1 by aluminium cation is linear mixed, with the cation being able to bind to
      both the free enzyme and the ES complex. This cation was the best hK1 inhibitor.
      Aluminium is not a physiological cation, but is a known neurotoxicant for animals
      and humans. The neurotoxic actions of aluminium may relate to neuro-degenerative
      diseases.

PMID- 15558948
TI  - Double-stranded RNA mediates selective gene silencing of protein phosphatase type
      1 delta isoform in HEK-293 cells.
AB  - The reversible phosphorylation of proteins mediates cellular signals in
      eukaryotic cells. RNA interference inhibits the expression of genes and proteins
      in a sequence-specific manner and provides a tool to study the functions of
      target molecules. The effect of RNA interference on protein phosphatase isoforms
      in HEK-293 cells was examined. Protein phosphatase 1 delta (PP1delta) sequence
      specific double-stranded RNA (dsRNA) inhibited mRNA and protein expression of the
      PP1delta. This RNA interference did not affect the expression of lphaand gamma1
      isoforms of PP1. Transfection of antisense RNA specific for PP1delta also
      suppressed the expression of PP1delta. It was further demonstrated by an in vitro
      RNA cleavage assay that extracts of HEK-293 cells catalyzed the processing of
      dsRNA. This cell line had much stronger mRNA expression of Dicer, an RNase III
      like enzyme, than did human osteoblastic MG63 cells. The present results show
      that RNA interference is a useful tool to distinguish between PP1 isoforms.

PMID- 15558949
TI  - Kinetic studies on Na+/K+-ATPase and inhibition of Na+/K+-ATPase by ATP.
AB  - Na+/K+-ATPase (EC 3.6.1.3) is an important membrane-bound enzyme. In this paper,
      kinetic studies on Na+/K+-ATPase were carried out under mimetic physiological
      conditions. By using microcalorimeter, a thermokinetic method was employed for
      the first time. Compared with other methods, it provided accurate measurements of
      not only thermodynamic data (deltarHm) but also the kinetic data (Km and Vmax).
      At 310.15K and pH 7.4, the molar reaction enthalpy (deltarHm) was measured as 
      40.514 +/- 0.9kJmol(-1). The Michaelis constant (Km) was determined to be 0.479
      +/- 0.020 mM and consistent with literature data. The reliability of the
      thermokinetic method was further confirmed by colorimetric studies. Furthermore,
      a simple and reliable kinetic procedure was presented for ascertaining the true
      substrate for Na+/K+-ATPase and determining the effect of free ATP. Results
      showed that the MgATP complex was the real substrate with a Km value of about
      0.5mM and free ATP was a competitive inhibitor with a Ki value of 0.253 mM.

PMID- 15558950
TI  - The inhibition of Clostridium chauvoei (jakari strain) neuraminidase activity by
      methanolic extracts of the stem barks of Tamarindus indicus and Combretum
      fragrans.
AB  - The inhibition of neuraminidase from Clostridium chauvoei (jakari strain) with
      partially purified methanolic extracts of some plants used in
      Ethnopharmacological practice was evaluated. Extracts of two medicinal plants,
      Tamarindus indicus and Combretum fragrans at 100-1000 microg/ml, both
      significantly reduced the activity of the enzyme in a dose-dependent fashion (P <
      0.001). The estimated IC50 values for Tamarindus indicus and Combretum fragrans
      were 100 and 150 microg/ml respectively. Initial velocity studies conducted,
      using fetuin as substrate revealed a non-competitive inhibition with the Vmax
      significantly altered from 500 micromole min(-1) mg(-1) to 240 micromole min(-1)
      mg(-1) and 340 micromole min(-1) mg(-1) in the presence of Tamarindus indicus and
      Combretum fragrans respectively. The KM remained unchanged at 0.42 mM. The
      computed Index of physiological efficiency was reduced from 1.19min(-1) to
      0.57min(-1) and 0.75min(-1) with Tamarindus indicus and Combretum fragrans as
      inhibitors respectively.

PMID- 15558951
TI  - Effect of some cardiac and respiratory drugs on succinate-cytochrome c reductase.
AB  - Succinate-cytochrome c reductase was inhibited in vitro and in vivo by
      phenobarbitone, aminophylline and neostigmine using both 2,6
      dichlorophenolindophenol (DCIP) and cytochrome c (cyt c) as substrates. The
      enzyme was also activated by gallamine towards both substrates. In vitro,
      phenobarbitone and aminophylline inhibited the enzyme with respect to the
      reduction of DCIP and cyt c in a non-competitive manner with Ki values of 1.5 x
      10(-5) and 5.7 x 10(-5)M, respectively. Moreover, neostigmine competitively
      inhibited the enzyme towards both substrates with Ki values of 1.36 x 10(-5) and
      1.50 x 10(-5)M, respectively.

PMID- 15558952
TI  - Mushroom tyrosinase inhibition by two potent uncompetitive inhibitors.
AB  - Two new bi-pyridine compounds, [1,4'] Bipiperidinyl-1'-yl-naphthan-2-yl-methanone
      (I) and [1,4'] Bipiperidinyl-1'-yl-4-methylphenyl-methane (II) were synthesized
      and examined for inhibition of the catecholase activity of mushroom tyrosinase in
      10 mM phosphate buffer pH 6.8, at 293 K using UV spectrophotometry. Inhibition
      kinetics indicated that they were uncompetitive inhibitors and the value of the
      inhibition constants were 5.87 and 1.31 microM for I and II, respectively, which
      showed high potency. Fluorescent studies confirmed the uncompetitive type of
      inhibition for these two inhibitors. The inhibition mechanism presumably comes
      from the presence of a particular hydrophobe site which can accommodate these
      inhibitors. This site could be formed due to a probable conformational change
      that was induced by binding of substrate with the enzyme.

PMID- 15558953
TI  - Investigation of the mutation points and effects of some drugs on glucose-6
      phosphate dehydrogenase-deficient people in the Erzurum region.
AB  - We have carried out a systematic study of the molecular basis of glucose-6
      phosphate dehydrogenase (G6PD) deficiency on three samples of 1,183 children aged
      0.5-6 years from Erzurum, in eastern Anatolia. Total genomic DNAs were isolated
      from the blood samples of a healthy person and the three persons determined with
      G6PD deficiency by examining the enzyme activity and hemoglobin ratio. Then PCR
      amplification of the entire coding region in eight fragments was carried out
      followed by Agarose gel electrophoresis. The 540-bp PCR fragment containing exons
      VI-VII and the 550bp PCR fragment containing exons XI-XIII were digested with
      EcoRI and with NIaIII, respectively. SSCP techniques for eight fragments (exons
      II, III-IV, V, VI-VII, VIII, IX, X, and XI-XIII) were employed to determine the
      mutations on the exons of the G6PD gene. A mutation occurred on the region of the
      exons 6 and 7 of one person (person-1) and exon 5 of two G6PD-deficient persons
      (person 2 and 3) examined. The sequential approach described is fast and
      efficient and could be applied to other populations. Effects of analgesic drugs
      on G6PD were studied on the purified enzyme (ammonium fractionation, dialysis and
      2',5' ADP-Sepharose 4B affinity chromatography) for the healthy person and G6PD
      deficient persons 1, 2 and 3. The effects of remifentanil hydrochloride, fentanyl
      citrate, alfentanil hydrochloride and pethidine hydrochloride, as analgesic
      drugs, on G6PD activity were tested. Although remifentanil hydrochloride,
      fentanyl citrate (I50 values; 1.45mM and 6.1 mM, respectively) inhibited the
      activity of the enzyme belonging to the healthy person, they did not alter enzyme
      activity on two of the three persons with G6PD deficiency. Other drugs
      (alfentanil hydrochloride and pethidine hydrochloride) did not effect the enzyme
      activity of the healthy or G6PD-deficient children.

PMID- 15558954
TI  - Effects of some antibiotics on human erythrocyte 6-phosphogluconate
      dehydrogenase: an in vitro and in vivo study.
AB  - The in vitro and in vivo effects of some antibiotics on human erythrocyte 6
      phosphogluconate dehydrogenase were investigated. Human erythrocyte 6
      phosphogluconate dehydrogenase was purified with ammonium sulphate precipitation,
      2',5' ADP-Sepharose 4B affinity and gel filtration chromatography. Some
      antibiotics (netilmicin sulphate, cefepime, amikacin, isepamycin,
      chloramphenicol, ceftazidim, teicoplanin, ampicillin, ofloxacin, levofloxacin,
      cefotaxime, penicillin G, gentamicin sulphate, ciprofloxacin) inhibited enzyme
      activity in vitro but others (cefozin, decefin, streptomycin, combisid, and
      meronem) were devoid of inhibitory effects. For the drugs having low IC50 values
      (netilmicin sulphate and cefepime), in vivo studies were performed in rats.
      Netilmicin sulphate at 15-mg/kg inhibited enzyme activity significantly (p <
      0.001) 1 h, 2 h, and 3 h after dosing and cefepime at 200-mg/kg very
      significantly (p < 0.001) inhibited the enzyme 1 h and 2 h after dosing.
      Netilmicin sulphate and cefepime inhibited rat erythrocyte 6-phosphogluconate
      dehydrogenase both in vivo and in-vitro.

PMID- 15558955
TI  - Synthesis and urease enzyme inhibitory effects of some dicoumarols.
AB  - Dicoumarols 1-10 with substituted phenyl residues at C-11 were synthesized and
      screened for their urease inhibition effects. All synthesized compounds showed
      varying degree of urease inhibitory activity ranging from IC50 = 74.30-91.35
      microM.

PMID- 15558956
TI  - Synthesis of coumarin derivatives with cytotoxic, antibacterial and antifungal
      activity.
AB  - The synthesis and selective biological screening of 7-hydroxy-4-methyl-2H-chromen
      2-one (2), 7-hydroxy-4,5-dimethyl-2H-chromen-2-one (15) and some of their
      derivatives were carried out. Compound 13 was found to be most potent cytotoxic
      agent with LD50 = 126.69 microg/ml. In antibacterial assay the compounds showed a
      broad spectrum of activities. Compound 11 exhibited a very high degree of plant
      growth inhibition at three levels of concentration. Compound 4 showed very
      promising antifungal activity against Candida albicans. Compounds 12 and 13
      demonstrated excellent antioxidant activity.

PMID- 15558957
TI  - Acetohydroxamate inhibition of the activity of urease from dehusked seeds of
      water melon (Citrullus vulgaris).
AB  - Urease from the seeds of watermelon (Citrullus vulgaris) was purified to apparent
      homogeneity, using two acetone fractionation steps, heat treatment at 48 degrees
      C and gel filtration through Sephadex G-200. Effect of acetohydroxamic acid (AHA)
      on the activity of the homogeneous enzyme preparation (sp. act. 3000 +/- 550U/mg
      protein) was investigated. AHA exhibited a concentration-dependent inhibition
      both in the presence and absence of the substrate. The inhibition was
      uncompetitive and the Ki was 2.5 mM. Binding of AHA with the enzyme was
      reversible, as 63% activity could be restored by dialysis. Time-dependent
      inhibition revealed a monophasic inhibition of the activity. Addition of beta
      mercaptoethanol (ME) gradually abolished the inhibition. Pre-treatment of native
      enzyme with 8.0 mM ME for 5 min at 30 degrees C exhibited protection against AHA
      induced inhibition. The significance of these observations is discussed.

PMID- 15558958
TI  - [Necrosing vasculitis].

PMID- 15558959
TI  - [Therapeutic use of stem cells. II. Adult stem cells].
AB  - Many degenerative diseases are not curable by means of classical medicine. The
      long term objective of cell therapy is to treat the patients with their own stem
      cells that could be either purified from the diseased organ or from "reservoirs"
      of stem cells such as that constituted by the bone marrow. The existence of stem
      cells in the organs or reservoirs is now established in vitro and in some cases,
      in animal models. Numbers of technical problems linked to the scarcity of these
      cells still delay the clinical use of purified stem cells. However, clinical
      protocols using heterogeneous cell populations have already started to treat a
      growing number of diseases. In some case, autologous cells can be used, as it is
      the case for bone marrow transplantation in blood diseases. Mesenchymal cells,
      also purified from the bone marrow are currently used in orthopaedic diseases.
      Because these cells reveal a broad differentiation potential, active research
      programs explore their possible use for treatment of other diseases. Bone marrow
      also contains vascular stem cells that could be active in reappearing defective
      vessels responsible for ischaemic diseases. Indeed, clinical trials in which bone
      marrow cells are injected in the cardiac muscle of patients with myocardial
      infarction or in the leg muscle (gastrocnemius) of patients with hind limb
      ischaemia have already started. Artificial skin prepared from skin biopsies is
      used for the reconstitution of the derma of severely burned patients. Clinical
      trials have also started, using allogenic cells. The patients must be treated by
      immunosuppressive drugs. Neurodegenerative diseases such as Parkinson have been
      successfully treated by intra-cerebral injection of foetal neurones. Pancreatic
      islets implanted in the liver have shown to re-establish a normal glycaemia in
      diabetic patients. However, all these clinical trials use differentiated cells or
      at least progenitors which display differentiation potential and lifetime much
      more restricted than those of stem cell. Numbers of laboratories are currently
      working to improve stem cell purification and expansion. This is a prerequisite
      to use these stem cells as a more efficient second generation cell therapy
      product.

PMID- 15558960
TI  - [Sickle cell disease: taking care of more and older patients].

PMID- 15558961
TI  - [Epidemiology of sickle cell anemia].
AB  - In France, 6000-7000 patients are suffering from sickle cell anemia in 2004. The
      number of patients in continental France exceeds the one found in the overseas
      regions. The highest frequency is found in the Parisian region where 185-200 new
      cases are annually diagnosed.

PMID- 15558962
TI  - [Sickle cell disease pathophysiology: from theoretical to practical aspects].
AB  - An up to date understanding of the sickle cell disease's pathophysiology needs a
      comprehensive approach of molecular cellular, vascular and genetic data. All
      those new knowledgeable domains give support to renewed therapeutic perspectives.
      However, the here given manuscript is limited to elementary pathophysiology
      leaving the other tissue specific or systemic complications fields.

PMID- 15558963
TI  - [Diagnosis and screening of sickle cell disease].
AB  - Hemoglobin S (HbS), which causes sickle cell disease, is now the most common
      genetic abnormality observed in France. Sickle cell disease is a generic term
      covering all the syndromes in which HbS is present. The heterozygous situation,
      named sickle cell trait, is perfectly well tolerated in contrast to homozygous or
      compound heterozygous forms, which lead to sickle cell anemia. To prevent
      complications, diagnosis of HbS has to be done as earlier as possible in the
      first day of life. This diagnosis is usually done by isoelectric focusing, or
      cellulose acetate electrophoresis at alkaline pH, but more and more frequently by
      cation exchange HPLC. It should always to be confirmed by a specific test for
      HbS, such as the solubility test or an electrophoresis on agar gel. In sickle
      cell anemia, it is important to evaluate the other factors that may modify the
      presentation (mostly HbF level and associated alpha-thalassemia). In a
      heterozygous subject presenting with pathological manifestations, more
      sophisticated biochemical tests or molecular biology investigations may be
      necessary to determine the cause of the disease.

PMID- 15558964
TI  - [Acute complications in sickle cell disease].
AB  - Sickle cell disease is an inherited disease characterised by the presence of an
      abnormal haemoglobin. Sickle cell disease can be complicated by acute vaso
      occlusive crisis, which are the major clinical problem prompting admission to
      hospital and the major cause of death. It mainly manifests by osteo-articular
      pain and acute chest syndrome and can be complicated by multi-organ failure. The
      main treatment of severe acute vaso-occlusive crisis is based on transfusion.

PMID- 15558965
TI  - [Chest syndrome: an acute respiratory distress produced by several factors].

PMID- 15558966
TI  - [Management of sickle cell disease].
AB  - Hypoxia, hemolysis and infection are more or less associated in patients affected
      with sickle cell disease. Treatment is based on a programme including regular
      lifestyle, hydration, folic acid supply, prevention of pneumococcal infections
      and cerebrovascular events in children, regular follow-up in specialised centres
      allowing precocious screening and treatment of organ deficiency. Some patients
      exhibit a severe form and need intensive preventive care, such as chronic
      transfusion, hydroxyurea or bone marrow transplantation for children and
      adolescent with an HLA-identical sibling. The choice between these strategies is
      multifactorial, excepted in patients with a severe cerebral vasculopathy, for
      whom chronic transfusion or bone marrow transplantation are preferable. We
      usually propose hydroxyurea as a first line treatment to patients with recurrent
      pain crises or acute chest syndromes. In cases of refusal, initial or secondary
      failure (which occur more frequently in adults), or intolerance of hydroxyurea,
      patients with a severe disease are chronically transfused, which leads them most
      of the time to necessitate iron chelation.

PMID- 15558967
TI  - [Hematopoietic stem cell graft: cure for sickle cell anemia?].

PMID- 15558968
TI  - [Osteo-articular complications of sickle-cell-anemia in adult].
AB  - Osteo-articular complications of sickle cell anaemia in adult are represented by
      bone marrow infarcts, osteomyelitis and osteonecrosis of femoral and humeral
      heads. The frequency and/or the severity of these complications provide a great
      functional disability in young patients whose life expectancy is growing. A well
      adapted treatment would may limit the sequels.

PMID- 15558969
TI  - [Hip prosthesis in sickle cell anemia: a delicate affair].

PMID- 15558970
TI  - [Infection in sickle cell disease].
AB  - Bacterial infection is frequent in patients with sickle cell disease.
      Pneumococcal bacteremia is particularly severe in young children. The risk
      persists in adults, especially for nosocomial infections. Prevention is directed
      against pneumococcal disease and includes both vaccination and prophylactic
      antibiotics.

PMID- 15558971
TI  - [Sickle cell disease and pregnancy].
AB  - Pregnancy in SCD women, with a major sickle cell syndrome, is a high-risk
      situation and is associated with raised incidence of maternal and fetal morbidity
      and mortality, mainly in late pregnancy, during delivery and in the postpartal
      periods. Pregnancy increases the incidence of sickle cell specific complications
      such as anaemia, vaso-occlusive crisis, abdominal, pulmonary (acute chest
      syndrome) or placental thrombosis, infections (urinary tract infection,
      pyelonephritis, pneumonia), and toxemia. Maternal death can occur. Sickle cell
      disease is responsible for high risk of spontaneous abortion, intra-uterine
      growth retardation, intra-uterine fetal death, preterm delivery, and perinatal
      mortality related to hypoxemia and placental thrombosis. More and more sickle
      cell affected women reach adulthood and reproductive age (fertility of sickle
      cell women is normal). The knowledge of these risks has contributed to the
      implementation of specific management program and to a better outcome of
      pregnancy. Such a program includes a close multidisciplinary approach for the
      duration of the pregnancy, the delivery and the postpartal period, in tertiary
      maternal health services level. Blood transfusion depends on teams and is related
      to strictly restricted maternal, obstetrical and hematologic indications.

PMID- 15558972
TI  - [Patient handout. Sickle cell anemia: what one must know].

PMID- 15558973
TI  - [Signs, diagnosis, treatment... evaluation].

PMID- 15558974
TI  - [Purpura of the child and the adult].

PMID- 15558975
TI  - [Current major ideas in psychiatry].

PMID- 15558976
TI  - [Addiction and drug associated behaviour. Epidemiology, prevention, surveillance.
      Morbidity, comorbidity and complications. Management, substitutive therapy and
      abstinence. 2nd part -- alcohol, psycho-active and illicit substances].

PMID- 15558977
TI  - [Self-medication].

PMID- 15558978
TI  - [The long story of sickle cell disease].

PMID- 15558979
TI  - [Day surgery in Italy (reflexions of a Past President who became such...)].

PMID- 15558980
TI  - [Colonic perforations after self-expandable metallic stenting: two case reports].
AB  - The use of self-expandable metallic stents in colorectal stenoses, both benign
      and malignant, is a recently born treatment, quickly widespread because of its
      simplicity and therapeutic efficacy. It is particulary useful, like emergency
      temporany treatment, in malignant colonic obstruction; in these cases the
      temporary endoprosthesis positioning allows the intestinal transit and to
      overcame the emergengy phase. After patient conditions improvement, he can be
      operated and the endoprosthesis removed within operating specimen. In some
      particularly serious cases, when only a derivative intervention is mandatory
      because of the general conditions of the patient or the advanced stadium of the
      illness, stenting can also represent definitive palliative treatment. In fact, it
      allows contemporary resolution of the occlusion and of the physiopathologic
      alterations, with hospital cost reduction and a quality life imprevement for the
      patient thanks to the colestomy absence. In benign pathologies, self-expandable
      stents are used for a long time in the superior gastrointestinal and biliary
      tract; now stents have found employment also for the treatment of the post
      operative fistula, intestinal diverticular occlusion and for the treatment of
      post-anastomotic or radiotherapy strictures. The Authors report two cases
      observed in emergency with complication determinated by positioning of colonic
      endoprosthesis for previous occlusive episode. The first case, a 56 year-old
      woman with a decubitus perforation occurred by stent, previously positioned with
      only palliative intent for a sigma-rectal metastatic cancer: in the second case,
      a 75 year-old man, the endoprosthesis had been positioned for a postoperative
      benign stricture of colorectal anastomosis for neoplasm: in this case the stent
      had determined a vescico-rectal fistula and after a new intestinal occlusion.

PMID- 15558981
TI  - [Free perforation in Crohn's disease].
AB  - Free perforation in abdominal cavity in patients with Crohn's disease is a rare
      entity as attested from the data reported in the literature. It is a very
      dangerous event and requires a surgical urgency management. The Authors reported
      two cases of free perforation, in patients with Crohn' disease, undergoing
      surgical operation in urgency. Analyzing pathogenesis, difficulty in diagnosis
      making and therapeutic choices, they underline that CT is very useful in the
      diagnosis, while resection of the perforated intestinal tract represent the best
      surgical treatment.

PMID- 15558982
TI  - [Intestinal obstruction due to perforated cecal volvulus. Case report].
AB  - Cecal volvulus is an uncommon cause of large-bowel obstruction. Its developement
      is due to an abnormal mobility of the ileocecal loop because of lacking
      attachement of ascending colon. Clinical features are frequently aspecific and
      should be differentiated from sigmoid volvulus and neoplastic obstruction.
      Therapy depends on visceral circulatory conditions at the moment of diagnosis.
      Possible options include endoscopic decompression, cecopexy with or without
      cecostomy, right colectomy with immediate or delayed anastomosis. The present
      paper reports the case of cecal volvulus in a 44 year old woman, successfully
      treated with right colectomy and primary anastomosis.

PMID- 15558983
TI  - [Surgical treatment of hydatid cysts].
AB  - Hydatidosis represents a form of helminthic zoonosis with a stronger medical,
      social and economic impact. It is endemic in some areas of the world including
      Mediterranean countries, and therefore Italy. The disease is often diagnosed in
      an advanced phase, due to the poor symptomatology in the early stages. The best
      treatment is surgery. Emergency surgery is similar to elective surgery, though in
      some cases is preferable only a drainage procedure until the stabilization of the
      genreal and local conditions of the patient allow a radical intervention. The
      Authors report on their five year experience of surgical treatment of compliated
      pulmonar hydatidosis pointing out that exeresis must be aimed at preserving
      pulmonar function as much as possible.

PMID- 15558984
TI  - [Varicose disease of lower limbs: our actual orientation].
AB  - A retrospective analysis of a series of patients treated during 5 years was made
      evaluating, on the basis of the clinical and ultrasonographic examination, the
      results obtained in the treatment of the varicose disease of the lower limbs for
      each one of three surgical methodic employed (crossectomy, long or short
      stripping) as well as patients compliance. All the patients previously underwent
      ultrasonographic examination to evaluate the reflux rank of the internal saphena
      and to point out every insufficient veins. On the basis of specific indications,
      from routinary pre-operative and anaesthesiologic examinations, all the patients
      were operated. Totally, 784 operations were performed. Thanks to the follow-up,
      carried out through an objective evaluation (echocolor-Doppler) and subjective
      one (degree of satisfaction fullfilled through some tests), it is concluded that
      the most favourable method, among those used, is that of short stripping with
      wrapping up a silk thread, in accordance to Van der Stricht.

PMID- 15558985
TI  - [A case of intestinal obstructions caused by a gossypiboma].
AB  - The Authors explain a case of intestinal obstruction due to a gossypiboma. They
      stress the great importance of the prevention in surgical operations (count of
      surgical towels, exploration of the surgical site) and the role of the
      differential diagnosis.

PMID- 15558986
TI  - [Surgical laparoscopic therapy of small bowel tumors: review of the literature
      and report of two cases].
AB  - The Authors, after a short review of small bowel tumors, point out that recently
      a laparoscopic approach for these tumors has been suggested and some cases have
      been reported. The Authors present two cases of patients operated for small bowel
      tumor using a laparoscopic technique: the first case for a stromal tumor (GIST),
      the second case for an adenocarcinoma in advanced stage with multilobar lung
      metastases. The first patient is alive and disease free after one year, the
      second died after six months for tumor progression. The Authors believe that
      laparoscopic technique can be employed with satisfying results also in the
      treatment of small bowel tumors with moderate trauma and invasiveness.

PMID- 15558987
TI  - [Laparoscopic adrenalectomy: our preliminary experience].
AB  - INTRODUCTION: In 1992, Gagner described the first laparoscopic adrenalectomy.
      Since then this technique has been more and more widely employed and several
      studies confirmed its advantages, comparing to the traditional approach, in terms
      of reduction of mean hospital stay and therefore of the health expense. PATIENTS
      AND METHODS: The Authors' preliminary experience spreads from March to November
      2003 when 4 patients were studied and thus underwent a transperitoneal
      laparoscopic adrenalectomy: 2 of them were affected by Cushing syndrome, 1 by
      pheochromocytoma in MEN and 1 by an incidentaloma. The transabdominal access in
      lateral decubitus with 4 trocars was performed. RESULTS: No complication was
      reported with a minimal need of analgesic drugs. The mean hospital stay was 4
      days and all patients were discharged 48 hours after surgery. The mean diameter
      of nodules was 40 +/- 30 mm. The definitive histological examination showed 2
      cortical adenomas, 1 diffuse cortical hyperplasia and 1 pheochromocytoma.
      CONCLUSIONS: This preliminary report confirms the optimal results of other
      experienced authors. Further interventions will be necessary for improvements and
      technical requirements.

PMID- 15558988
TI  - [The role of intraoperative parathyroid hormone assay in the surgical management
      of hyperparathyroidism].
AB  - Surgical management of primary hyperparathyroidism has undergone several chances
      in recent years and historically has required bilateral neck exploration with
      identification of the parathyroid adenoma together with three normal glands. The
      intraoperative hormone assay allows a more limited procedure by confirming
      complete removal of hypersecreting tissue. The Authors report surgical treatment
      of 24 consecutive hyperparathyroidism and conclude that evaluation of
      intraoperative hormone assay accurately predicts the determination of adequacy of
      resection and the correct outcome of surgery in patients with parathyroid
      adenomas.

PMID- 15558989
TI  - [The abdominal wall: an overlooked cause of pain].
AB  - Abdominal wall pain is frequently misdiagnosed as arising from visceral source,
      often resulting in inappropriate diagnostic tests, unsatisfactory treatment and
      high costs. The Authors describe the various causes of abdominal wall pain with
      particular regard to abdominal cutaneous nerve entrapment syndrome. They analyze
      the main features of abdominal wall pain: a localized tender trigger point can be
      frequentely identified, the Carnett's sign is positive and the local injection of
      an anesthetic agent into the trigger point can be diagnostic and therapeutic,
      while image techniques are useful when the pain results from structural
      conditions. At last they describe the therapeutic options.

PMID- 15558990
TI  - [Ileum-colon junction benign obstructions].
AB  - The Authors discuss on anatomical and functional characteristics of ileum-colon
      junction, physiological narrowing in alimentary tract and often involved in
      benign obstruction. They report their series and analyze all inflammatory or not
      inflammatory diseases potentially involved, by describing them shortly and giving
      some information about their clinical features and imaging. The treatment of this
      obstruction will be done as soon as possible, before wall lesions force to make a
      larger resection.

PMID- 15558991
TI  - Sleep deficit and stress hormones in helicopter pilots on 7-day duty for
      emergency medical services.
AB  - INTRODUCTION: Helicopter-based emergency medical services in Germany operate from
      sunrise to sunset, requiring up to 15.5 h of continuous duty during the summer
      months for pilots, who work for seven consecutive days. Because of concerns
      regarding the safety of this procedure with respect to pilot fatigue and stress,
      the German Ministry of Transport asked our laboratory to investigate the risks
      involved. METHODS: There were 13 pilots (mean age 38 yr) who were studied in the
      summer months for 2 d before, 7 d during, and 2 d after their duty cycle.
      Measured variables included sleep duration and quality, subjective fatigue, and
      heart rate, as well as 24-h excretion levels of stress hormones. RESULTS: During
      actual helicopter operations, maximum heart rates did not exceed 120 bpm. Over
      the 7-d duty period, mean sleep duration decreased from 7.8 h to 6 h or less,
      resulting in a cumulative sleep loss of about 15 h. Mean levels of excreted
      adrenalin, noradrenalin, and cortisol increased significantly by 50 to 80%;
      cortisol and noradrenalin excretion also remained elevated for the two post-duty
      days. CONCLUSIONS: Although the actual flights did not cause critical
      physiological responses, the acute and accumulated sleep deficit led to
      incomplete recuperation between duty hours and induced elevated stress
      indicators. It was, therefore, recommended that the duty cycle be amended as
      follows: 1.) enforce a 10-h rest period and at least an 8-h sleep opportunity per
      day; 2.) modify the duty period to allow no more than 3 consecutive rest periods
      of reduced sleep opportunities (8.5 h); and 3.) follow duty with several days
      that offer unrestricted sleep opportunities.

PMID- 15558992
TI  - Eccentric exercise prior to hindlimb unloading attenuated reloading muscle damage
      in rats.
AB  - INTRODUCTION: Antigravity muscles that are reloaded subsequent to hindlimb
      unloading (HU) are prone to injury. Similarities exist between muscle damage
      elicited from HU and subsequent reloading and damage induced by eccentric
      exercise (EE). Conditioning bouts of EE reduce muscle damage following a repeat
      bout of EE. Since damage to reloaded skeletal muscle is comparable to damage
      observed after EE, the mechanisms of damage are presumably similar. Therefore, EE
      prior to HU may attenuate reloading muscle damage. This study evaluated the
      effects of prior EE on rat soleus muscles (SOL) subsequent to 7 d of HU and 16-19
      h of reloading. METHODS: Sprague Dawley rats were randomly assigned to the
      following groups: eccentric exercise + hindlimb unloading + reloading (EEHUR; n =
      9); hindlimb unloading + reloading (HUR; n = 10); eccentric exercise (EE; n =
      12), or control (CON; n = 12). The exercise protocol was performed 5 d x wk(-1)
      for 2 wks followed by HU and reloading. RESULTS: Fiber areas were lower in both
      suspended groups vs. the EE and CON groups. There was no difference in percent
      interstitial area among groups. However, percent myofibrillar damage was higher
      in the HUR group vs. all other groups. Further, glucose-6-phospate dehydrogenase
      activity, an indicator of muscle damage, was higher in the HUR group compared
      with the EE and CON groups. CONCLUSION: These results provide some evidence that
      prior EE reduced muscle damage subsequent to HU and reloading. Therefore, EE may
      prove effective in minimizing recovery time in individuals suffering from muscle
      damage following periods of bed rest and spaceflight.

PMID- 15558993
TI  - Head down tilt at -6 degrees to -24 degrees can neutralize the cardiovascular
      effects of LBNP at -15 or -35 mmHg.
AB  - INTRODUCTION: The purpose of this study was to identify the combinations of head
      down tilt (HDT) and lower body negative pressure (LBNP) that would counterbalance
      each other's effects on cardiovascular and endocrine variables to produce a
      "neutral point" (NP). METHODS: We conducted 8 30-min experiments in 14
      normotensive subjects (2 male, 12 female). Conditions included four levels of HDT
      (-6 degrees to -24 degrees) and two of LBNP (-15 and -35 mmHg). We determined
      blood plasma mass density, hematocrit, plasma aldosterone concentration, and
      plasma renin activity (PRA) before and at the end of stimulation. The effect of
      stimulus duration was tested using continuous measurements of heart rate (HR),
      blood pressure (BP), and thoracic electrical impedance (Z0). RESULTS: NPs were
      found for all variables except BP, which remained unchanged. NPs were similar for
      all variables. The 15 mmHg LBNP was compensated by 20 degrees HDT and 35 mmHg
      LBNP by 27.5 degrees HDT. Longer stimulus duration required increasing HDT angles
      to balance HR at 35 mmHg LBNP but had no influence on Z0 NP. DISCUSSION:
      Antiorthostatic positioning can compensate cardiovascular effects of LBNP in a
      similar fashion for all variables that are significantly influenced by LBNP and
      body angle, commensurate with stimulus magnitude. Arterial BP remained stable
      with stimulation and seems to be the primarily defended variable. Why stimulus
      duration seems to influence the NP for HR remains to be elucidated.

PMID- 15558994
TI  - Hearing thresholds during Gz acceleration with masking noise.
AB  - BACKGROUND: Future fighter aircraft will include three-dimensional sound signals
      as part of the human-machine interface. The reduction in cerebral vascular flow
      associated with maneuvering acceleration (+Gz) may affect a pilot's ability to
      perceive and interpret such aural cues. We hypothesized that vascular deprivation
      along the cochlea produced by +Gz would raise hearing thresholds either globally
      or specifically at 1000 Hz. METHODS: We compared hearing thresholds for pure
      tones at 250, 1000, 6000 and 10,000 Hz during exposure to +1 Gz vs. +4 Gz.
      Experiments were conducted with steady noise input to the earphones to mask
      centrifuge noise. RESULTS: Paradoxically the hearing threshold was slightly yet
      significantly reduced for 1000 Hz (53 dB at 1 G vs. 47 dB at 4 G) while remaining
      unchanged at other frequencies. DISCUSSION: Audition did not change at +4 Gz,
      contradicting our hypothesis. We infer that the change at 1000 Hz is not a
      central effect, but instead represents a disturbance of middle ear transmission
      mechanisms. The absence of any general hearing loss at +4 Gz favors the
      possibility of using complex sounds such as three-dimensional sound in
      aeronautical human-machine interfaces during acceleration.

PMID- 15558995
TI  - Warming by immersion or exercise affects initial cooling rate during subsequent
      cold water immersion.
AB  - INTRODUCTION: We examined the effect of prior heating, by exercise and warm-water
      immersion, on core cooling rates in individuals rendered mildly hypothermic by
      immersion in cold water. METHODS: There were seven male subjects who were
      randomly assigned to one of three groups: 1) seated rest for 15 min (control); 2)
      cycling ergometry for 15 min at 70% Vo2 peak (active warming); or 3) immersion in
      a circulated bath at 40 degrees C to an esophageal temperature (Tes) similar to
      that at the end of exercise (passive warming). Subjects were then immersed in 7
      degrees C water to a Tes of 34.5 degrees C. RESULTS: Initial Tes cooling rates
      (initial approximately 6 min cooling) differed significantly among the treatment
      conditions (0.074 +/- 0.045, 0.129 +/- 0.076, and 0.348 +/- 0.117 degrees C x
      min(-1) for control, active, and passive warming conditions, respectively);
      however, secondary cooling rates (rates following initial approximately 6 min
      cooling to the end of immersion) were not different between treatments (average
      of 0.102 +/- 0.085 degrees C x min(-1)). Overall Tes cooling rates during the
      full immersion period differed significantly and were 0.067 +/- 0.047, 0.085 +/-
      0.045, and 0.209 +/- 0.131 degrees C x min(-1) for control, active, and passive
      warming, respectively. DISCUSSION: These results suggest that prior warming by
      both active and, to a greater extent, passive warming, may predispose a person to
      greater heat loss and to experience a larger decline in core temperature when
      subsequently exposed to cold water. Thus, functional time and possibly survival
      time could be reduced when cold water immersion is preceded by whole-body passive
      warming, and to a lesser degree by active warming.

PMID- 15558996
TI  - Thermal and metabolic responses of sleep deprivation of humans during acute cold
      exposure.
AB  - PURPOSE: This investigation evaluated the effects of 33 h of sleep deprivation on
      the thermoregulation in 12 male and female subjects (26.6 +/- 6.4 yrs) during 180
      min of cold exposure in 12 degrees C air. METHODS: Subjects underwent two cold
      air trials (CAT): one following a normal night of sleep (i.e., 6-8 h) (CON); and
      one following 33 h of sleep deprivation (SDEP). Rectal temperature (Tre), mean
      skin temperature (Tsk), heat production (HP), and tissue insulation (Iti), were
      measured at 5, 15, 30, and every 30 min thereafter. RESULTS: ANOVA revealed no
      significant differences (p > 0.05) between CON and SDEP for Tre, Tsk, HP, and
      Iti. A main effect for time was demonstrated for Tre, Iti, HP, and Tsk. A trial x
      time interaction for Tre and Tsk (p = 0.021) was demonstrated. DISCUSSION:
      Significant interactions were demonstrated for Tre and Tsk, but post hoc analysis
      determined no differences between SDEP and CON. This may have been due to the
      length of the sleep deprivation, cold stressor, or a combination of the two.
      There were also no overall differences in HP or Iti between SDEP and CON. Further
      research in this area is needed to evaluate the effects of sleep deprivation
      during acute cold exposure.

PMID- 15558997
TI  - Central nervous system decompression sickness and venous gas emboli in hypobaric
      conditions.
AB  - INTRODUCTION: Altitude decompression sickness (DCS) that involves the central
      nervous system (CNS) is a rare but potentially serious condition. Identification
      of early symptoms and signs of this condition might improve treatment. METHODS:
      We studied data from 26 protocols carried out in our laboratory over the period
      1983-2003; all were designed to provoke DCS in a substantial proportion of
      subjects. The data set included 2843 cases. We classified subject-exposures that
      resulted in DCS as: 1) neurological DCS of peripheral and/or central origin
      (NEURO); 2) a subset of those that involved only the CNS (CNS); and 3) all other
      cases, i.e., DCS cases that did not have a neurological component (OTHER). For
      each case, echo imaging data were used to document whether venous gas emboli
      (VGE) were present, and their level was classified as: 1) any level, i.e., Grade
      1 or higher (VGE-1); and 2) high level, Grade 4 (VGE-4). RESULTS: There were 1108
      cases of altitude DCS in the database; 218 were classified as NEURO and 49 of
      those as CNS. VGE-1 were recorded in 83.8% of OTHER compared with 58.7% of NEURO
      and 55.1% of CNS (both p < 0.001 compared with OTHER). The corresponding values
      for VGE-4 were 48.8%, 37.0%, and 34.7% (p < 0.001, compared to OTHER). Hyperbaric
      oxygen (HBO) was used to treat about half of the CNS cases, while all other cases
      were treated with 2 h breathing 100% oxygen at ground level. DISCUSSION: Since
      only about half of the rare cases of hypobaric CNS DCS cases were accompanied by
      any level of VGE, echo imaging for bubbles may have limited application for use
      as a predictor of such cases.

PMID- 15558998
TI  - Cross-cultural differences in psychosocial adaptation to isolated and confined
      environments.
AB  - INTRODUCTION: Differences in patterns of psychosocial adaptation under conditions
      of prolonged isolation and confinement in Antarctica were examined to determine
      the extent to which they were influenced by national culture in general and the
      individualist-collectivist orientation of national cultures in particular.
      METHODS: The Profile of Mood States and measures of structural and functional
      social support were administered over an 8-mo period (March through October) to
      13 winter-over crews from 5 nations operating research stations in the Antarctic:
      United States (3 crews, n = 77), Poland (3 crews, n = 40), Russia (3 crews, n =
      34), China (3 crews, n = 40), and India (1 crew, n = 26). RESULTS: Americans at
      South Pole Station reported significant increases in fatigue and anxiety and a
      significant decrease in vigor over the winter. During the same period, Russians
      at Vostok Station reported significant decreases in depression, anxiety, and
      confusion, and Indians at Maitri Station reported a significant decrease in
      anger. A significant decrease in social interaction with fellow crewmembers
      occurred at South Pole Station, Vostok Station, and Poland's Arctowski Station.
      Several differences were also observed between the five stations in correlations
      between mood scores and measures of structural and functional social support. An
      individualistic cultural orientation was significantly associated with low social
      support and low negative mood. CONCLUSION: Cultural background is associated with
      mood and social support as well as changes in these measures during the austral
      winter. Cultural differences in patterns of psychosocial adaptation must be
      considered in the formation and training of multinational crews for long duration
      missions in space.

PMID- 15558999
TI  - Renin angiotensin aldosterone system and ACE I/D gene polymorphism in high
      altitude pulmonary edema.
AB  - INTRODUCTION: People who visit high altitude are exposed to a stressful
      environment, and many of them suffer from altitude-induced conditions, including
      high altitude pulmonary edema (HAPE). We investigated the renin angiotensin
      aldosterone system (RAAS) and the possible association of angiotensin converting
      enzyme (ACE) insertion/deletion (I/D) gene polymorphism in the development of
      HAPE in Indian men. METHODS: Subjects were all low-altitude natives: 19 men who
      developed HAPE within 1-3 d of arrival at 3000 to 3800 m (patients); and 20 age
      matched men who did not develop HAPE during a period of a month or more at > or =
      3500 m (controls). We recorded the arterial oxygen saturation (Sao2), heart rate
      (HR), and blood pressure (BP) of both groups and measured their levels of plasma
      renin activity (PRA), ACE, aldosterone, and serum electrolytes. Polymerase chain
      reaction was used to investigate a 287 base pair alu repeat sequence I/D
      polymorphism in the ACE gene. RESULTS: Compared with controls, patients showed a
      significantly lower Sao2 and a higher HR. They also had significantly higher
      plasma PRA, aldosterone, ACE, and serum sodium (Na+) and potassium (K+). No
      significant difference was observed in ACE I/D allele frequencies. DISCUSSION:
      The results suggested that RAAS is involved in the development of HAPE in low
      altitude natives, but there is no association of ACE I/D gene polymorphism with
      HAPE.

PMID- 15559000
TI  - Alaska air carrier operator and pilot safety practices and attitudes: a statewide
      survey.
AB  - INTRODUCTION: Aviation crashes are a leading cause of occupational fatalities in
      Alaska, with Alaskan pilots having nearly 100 times the fatality rate of U.S.
      workers overall. A survey was designed to study pilot and company practices and
      attitudes in order to develop intervention strategies that would reduce aviation
      fatalities. METHODS: Two surveys were administered: one of air carrier operators
      and one of active commercial pilots. Surveys from 153 air taxi and public-use
      operators were received at a 79% response rate. RESULTS: There are almost 2000
      pilots employed in Alaska during peak season by air taxi operators and public
      agencies. Surveyed operators and pilots generally agreed that improved weather
      information and regional hazards training would be effective ways to prevent
      crashes. Operators were more in favor of operator financial incentives (p < 0.05)
      and better pre-employment hiring checks on pilots (p < 0.05) compared with
      pilots' survey responses. There were 48% of pilots of large operators and 73% of
      pilots of small operators who considered their jobs to be at least as safe as
      other jobs. CONCLUSIONS: The results of operator-pilot comparisons suggest that
      financial pressures on operators may influence their views on what measures would
      be effective in preventing crashes, and that Alaskan pilots underestimate their
      occupational fatality risk.

PMID- 15559001
TI  - Seizure incidence in 80,000 patient treatments with hyperbaric oxygen.
AB  - INTRODUCTION: Hyperbaric oxygen treatment (HBOT) involves some risk of central
      nervous system (CNS) oxygen toxicity, which may be revealed by various signs and
      symptoms including seizures in patients breathing O2 at pressures of 2 ATA or
      higher. The aim of this study was to determine the incidence of such seizures in
      the Underwater and Hyperbaric Medicine Departments of two university hospitals.
      METHODS: We retrospectively evaluated 80,679 patient-treatments for 9 clinical
      indications to determine the incidence of seizures attributable to CNS O2
      toxicity. Because different protocols were used for HBOT, the treatments were
      studied in four groups according to the chamber type used and the medical
      facility at which it was located. RESULTS: Only 2 seizures were documented,
      yielding an incidence of 2.4 per 100,000 patient-treatments. Both cases occurred
      in a multiplace chamber pressurized to 2.4 ATA with O2 delivered by mask for
      three x 30 min with 5-min air breaks. DISCUSSION: The seizure incidence reported
      here is lower than other studies published in the literature. The delivery of O2
      by mask rather than hood may be a factor. Nevertheless, it appears that the risk
      of seizures due to CNS O2 toxicity during HBOT is very low as long as appropriate
      exclusion criteria and treatment profiles are used.

PMID- 15559002
TI  - Risk vs. benefit in hyperbaric medicine: a brief comment.

PMID- 15559003
TI  - Oral drug therapy for erectile dysfunction: overview and aeromedical
      implications.
AB  - Approximately 150 million men worldwide experience erectile dysfunction, whereby
      they are unable to maintain an erection adequate for satisfactory sexual
      performance. This population is projected to more than double in the next 25 yr.
      Introduction of the phosphodiesterase inhibitors has revolutionized the
      management of this common problem, encouraging many more men to seek treatment.
      The issue of erectile dysfunction treatment is a growing concern in the aviation
      community as well. This is particularly relevant in civil aviation, as this
      population is older and has co-morbidities that may contribute to the development
      of erectile dysfunction. In this article we will review the available options for
      oral treatment of erectile dysfunction and discuss implications regarding their
      use in aviators based on the information available in the literature.

PMID- 15559004
TI  - Multiple sclerosis initially presenting as facial palsy.
AB  - A case of multiple sclerosis initially presenting as a facial palsy is presented.
      A 35-yr-old U.S. Air Force aviator developed a purely right-sided facial palsy
      with no sensory abnormalities. She had no other neurologic findings except for a
      barely perceptible loss of coordination in her right upper extremity. Subsequent
      brain MRI revealed multiple white matter lesions. Further history and laboratory
      analysis confirmed multiple sclerosis. This case underscores the potential for
      multiple sclerosis to mimic other more benign conditions and the need for
      clinicians to carefully examine patients presenting with new neurologic
      abnormalities. The diagnosis and treatment of multiple sclerosis as well as
      military aviation policy regarding multiple sclerosis patients is discussed.

PMID- 15559005
TI  - Cases from the aerospace medicine residents' teaching file: furunculosis.
AB  - A case is presented of an aviator with frequent dermatologic lesions concerning
      for recurrent furunculosis that was caused by community-acquired methicillin
      resistant Staphylococcus aureus. The presentation, diagnosis, treatment, and
      aeromedical disposition of recurrent furunculosis are discussed.

PMID- 15559006
TI  - You're the flight surgeon. The flight surgeon is the key component in ensuring
      the aviation population is physically and mentally fit to fly.

PMID- 15559007
TI  - President's page. 1st Annual FAA International Aviation Safety Forum: leading to
      new levels.

PMID- 15559008
TI  - This month in aerospace medicine history--October 2004.

PMID- 15559009
TI  - [Omega-3 fatty acids, new treatment for depression].

PMID- 15559010
TI  - [Stem cells as spare parts for humans, tomorrow's promise or nonsense].

PMID- 15559011
TI  - [Adenoidectomy--is it unnecessary surgery toward preventing otitis?].

PMID- 15559012
TI  - [Apostles of being dirty are becoming popular].

PMID- 15559013
TI  - [Sociosomatics--a novel view on the management of pleiotropic symptoms].

PMID- 15559014
TI  - [Facial pain--a complicated problem].

PMID- 15559015
TI  - [Diagnostic criteria for Meniere's disease].

PMID- 15559016
TI  - [Hallucination--a neurologic or psychiatric disorder?].

PMID- 15559017
TI  - [What every doctor should learn from psychiatry].

PMID- 15559018
TI  - [Infant mortality in Finland during the years of 1969-1996].

PMID- 15559019
TI  - [Diet as medical treatment for diabetes].

PMID- 15559020
TI  - [Yellow nail syndrome causing repeated pleural effusion].

PMID- 15559021
TI  - [Brain abscess].

PMID- 15559022
TI  - [Acute otitis].

PMID- 15559023
TI  - [Hyperthyroidism of a young women].

PMID- 15559024
TI  - Garlic: its cardio-protective properties.
AB  - Evidence that garlic inhibits platelet aggregation, increases fibrinolysis,
      reduces blood pressure, enhances anti-oxidant activity, and reduces serum lipids
      suggests that it may have cardio-protective properties. The lack of qualitative
      standardization of garlic preparations and the methodological weaknesses of
      earlier studies makes comparison between different studies complicated.
      Quantitative pooling of data in meta-analyses of the primary trials strongly
      suggests that garlic is an effective lipid-lowering agent.

PMID- 15559025
TI  - Nuts: a new protective food against coronary heart disease.
AB  - Recent epidemiological findings indicate that frequent nut consumption offers
      protection from fatal and non-fatal coronary heart disease events. Although human
      nutrition studies seem to indicate that nut consumption lowers total and LDL
      cholesterol, the unique nutrient composition of nuts invites speculation on other
      mechanisms of protection.

PMID- 15559026
TI  - Vegetarianism, coronary disease risk factors and coronary heart disease.
AB  - Recent studies of vegetarians confirm a lower risk of fatal heart disease amongst
      such subjects. Lipid levels are lower in vegetarians, even when the diet of
      comparable meat-eaters is low in fat. This may partly explain the lower
      mortality, but it is not clear whether the absence of meat or some other aspect
      of the vegetarian diet is causal in this relationship.

PMID- 15559027
TI  - Copper: an antioxidant nutrient for cardiovascular health.
AB  - Dietary copper often is low in the Western diet; low intakes may affect all
      stages of atherosclerosis adversely. Impaired oxidative defense in copper
      deficiency contributes to hypercholesterolemia, hypertension, and impaired
      prostaglandin metabolism. Free copper ion does not exist in vivo; some in-vitro
      experiments are conducted with millions-fold excesses.

PMID- 15559028
TI  - Interaction between diet, exercise and lipids or lipoproteins.
AB  - Diet can influence the changes in plasma lipoprotein concentrations that occur
      with exercise. Dietary factors alone, however, probably do not account for the
      lipoprotein profiles of physically active people. Whether exercise or diet exerts
      the dominant effect on lipids and lipoproteins depends largely on the level of
      exercise achieved and the total energy balance. More well designed research is
      required to examine the effect of diet on lipids and lipoproteins in people of
      different levels of physical fitness taking part in a variety of physical
      activities.

PMID- 15559029
TI  - New approaches to achieving dietary change.
AB  - Current approaches to achieving dietary change are reviewed. The more successful
      strategies are those that are tailored to the individual and his or her situation
      and readiness for change, supported when possible by broader social and
      environmental changes. Some methods of reducing dietary fat intake are better
      accepted and maintained than others; an emphasis on these may be helpful.

PMID- 15559030
TI  - Hypertriglyceridemia and low HDL: therapeutic considerations.
AB  - The recently revised guidelines for cholesterol management in Europe and the USA
      have focused attention on triglycerides and HDL cholesterol as risk factors for
      coronary heart disease. In the present review, I shall discuss therapeutic
      considerations in the treatment of patients with hypertriglyceridemia or low HDL
      cholesterol in the context of these new recommendations. I shall also consider
      recent studies in which the effect of triglyceride-lowering drugs on the
      concentrations and metabolism of lipoproteins in patients with dyslipidemia are
      evaluated.

PMID- 15559031
TI  - Post-menopausal hormone replacement therapy, coronary heart disease and plasma
      lipoproteins.
AB  - At least 20 million postmenopausal women worldwide now use some form of hormone
      replacement therapy. This figure is increasing because the resistance of the
      medical community to these therapies is diminishing and because of increasing
      acknowledgement of the benefits of such therapies on the cardiovascular system.
      This is a remarkable development for a medication originally used to relieve
      menopausal symptoms such as hot flushes and to prevent bone loss. Although
      several mechanisms are now accepted to be involved in this protection from
      cardiovascular disease, changes in plasma lipoproteins remain a major area of
      research interest. The main issue in this field, whether the addition of a
      progestogen to postmenopausal oestrogen ('combined therapy') will diminish the
      benefits on the cardiovascular system, remains unresolved, but combined therapies
      have now been formulated that minimize the potentially detrimental effects of
      progestogens on plasma lipoproteins. Recent findings of interest include the
      effects of these therapies on plasma lipoprotein (a) concentration and on LDL
      particle size. Studies of the mechanisms behind such changes are needed.

PMID- 15559032
TI  - HMG CoA reductase inhibitors.
AB  - Beta-hydroxy-beta-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (HMG
      CoA RIs) are now being prescribed in many different countries, and the number of
      patients treated with these compounds is estimated to be over 1.5 million. The
      spectrum of indications for these drugs is enlarging. Thus, not only patients
      with primary hypercholesterolemia are suitable candidates for therapy with HMG
      CoA RIs, but also patients with other forms of familial and non-familial
      (secondary) dyslipidemias. The safety and tolerance profile is remarkably good
      and adverse effects tend to be mild and rare. Currently, several primary and
      secondary intervention trials are ongoing or in preparation to investigate the
      influence of HMG CoA RIs on cardiovascular morbidity and mortality.

PMID- 15559034
TI  - Bibliography of the current world literature. Nutrition and therapeutics.

PMID- 15559033
TI  - Advances in LDL-apheresis for the treatment of severe hypercholesterolemia.
AB  - LDL-apheresis is an extracorporeal plasma-perfusion method that selectively
      removes apolipoprotein B-containing lipoproteins from the blood. It is indicated
      for patients with homozygous and drug-resistant heterozygous familial
      hypercholesterolemia. Clinical and angiographic regression of coronary artery
      disease has been demonstrated in patients treated with cholesterol-lowering
      programs that include LDL-apheresis.

PMID- 15559035
TI  - Nutrition and therapeutics.

PMID- 15559036
TI  - Genetics and molecular biology.

PMID- 15559037
TI  - Lipid metabolism.

PMID- 15559038
TI  - Cardiovascular disease and hyperlipidaemia.

PMID- 15559039
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 15559040
TI  - Clinical chemistry and coagulation.

PMID- 15559041
TI  - The culture of technology: defining transformation in nursing, from "the lady
      with a lamp" to "robonurse"?

PMID- 15559042
TI  - Learning and change among leaders of a professional nursing association.
AB  - This is a report of the results of a qualitative research study that investigated
      the informal learning and changes experienced by 20 members of an exemplary
      chapter of critical care nurses as they advanced from being new members to
      becoming officers and board members. Qualitative research methods were used that
      included analysis of critical incidents, documents, and individual interviews.
      Methods used, results of the study, and conclusions and recommendations are
      discussed.

PMID- 15559043
TI  - Nurturing the transformation from staff nurse to leader.
AB  - A major component of nurse job satisfaction is autonomy of clinical practice,
      recognition by colleagues, and participation in decision making relative to
      patient outcomes. Shared governance provides the framework for autonomy and
      control of practice, yet implementation of this model implies staff participation
      as leaders. Staff nurses describe a transformation of perspective when adopting
      decision-making, leadership-oriented roles and recount the factors that influence
      and nurture their confidence and acceptance.

PMID- 15559044
TI  - An extended epistemology for fostering transformative learning in holistic
      nursing education and practice.
AB  - The transformation from traditional nursing practice to holistic nursing is one
      that requires recognition of multiple ways of knowing. Transformative learning
      theory reflects a strong bias toward cognitive epistemology and propositional
      knowing. This epistemology, labeled here as truncated, rests on an understanding
      of experience derived from pragmatism. This article describes an extended
      epistemology derived from the work of John Heron that better reflects the full
      range of knowing utilized by holistic nurses. This epistemology provides a
      foundation for innovative approaches for the development of holistic awareness in
      the training and continuing professional development of nurses. One such
      approach, collaborative inquiry, is described.

PMID- 15559045
TI  - Peer-based professional development viewed through the lens of transformative
      learning.
AB  - The goal of professional development is improved practice through change-changes
      in ways of doing or thinking about one's work. Traditional approaches, including
      group instruction and individualized coaching, emphasize the unidirectional flow
      of information from expert to novice. This article foregrounds a nontraditional
      peer-based modality, the peer learning partnership, which promotes joint
      reflection and reciprocal learning between professionals. A qualitative case
      study of a peer-based community college faculty development initiative reveals
      participants' perceptions of the role peer partnering played in their learning.
      Findings are discussed relative to selected theories, specifically transformative
      learning. Recommendations are offered on using peer-based approaches for
      professional development and transformation.

PMID- 15559046
TI  - Learning in clinical nursing practice.
AB  - In this study, a qualitative interpretivist perspective was used to analyze the
      following research question: How does clinical nursing practice facilitate
      learning? Forty nurses working in acute care, long-term care, and home care were
      interviewed about their clinical practice experiences and the learning that
      resulted. Data were analyzed using a constant comparative method. Study results
      indicate that clinical nursing practice facilitates both personal and
      professional development of nurses by fostering an examination of the concepts of
      self-respect, hope, control, vulnerability, acceptance, loss, and persistence.
      Implications for continuing educators and staff development instructors are
      drawn.

PMID- 15559047
TI  - Culture care conflicts among Asian-Islamic immigrant women in US hospitals.
AB  - Muslims follow their Islamic traditions as they integrate into the US society.
      Islamic beliefs are reflected in everyday life, and care is viewed within a
      holistic context. A lack of understanding of Muslims and their cultural and
      religious traditions contributes to potential conflicts in health care. The five
      concepts of Islamic beliefs from the religious texts of the Qur'an, Sunnah, and
      Hadith will be discussed followed by the implication of these beliefs for
      clinical practice. Knowledge of these Islamic cultural and religious beliefs will
      help reduce potential culture care conflicts among Asian-Islamic immigrant women
      in US hospitals.

PMID- 15559048
TI  - Perceived health status in African American and Caucasian men 40 to 70 years old.
AB  - There is limited data on the relationship between perceived health status and the
      demographic variables of education and income in African American men. A sample
      of 2,001 men (72% African Americans and 28% Caucasians) who were participating in
      prostate cancer screening was studied to identify predictors of men's health
      status. Data on the concepts of self-rated health status, age, race, education,
      income, living arrangements, and marital status were collected. Findings
      indicated that men who were more likely to report excellent health status were
      older Caucasians, had more than a high school education, an annual income over
      25,021 dollars, were living with others, and were married. Men more likely to
      report fair health status were older African Americans, unmarried, had less than
      a high school education, had an annual income less than 9,600 dollars, were
      living alone, and were unmarried. Implications for targeting at-risk men are
      presented.

PMID- 15559049
TI  - Meaning of Ki related to touch in caring.
AB  - In an attempt to identify the concept of Ki related to touch within the context
      of caring, and further, to provide specific information that may lead to
      culturally sensitive nursing intervention for the population who relate the
      concept of Ki to touch in a caring situation, a qualitative analysis was planned
      and carried out. Data was collected using interactive interviews with 19 health
      care professionals, 4 alternative therapists, 10 inpatients, and 13 healthy
      adults, and analyzed by the latent content analysis. Ki, the interactive energy
      flow, and touch, the activator of Ki flow, were postulated from six categories of
      perceived meanings of Ki related to touch.

PMID- 15559050
TI  - Malignant pleural mesothelioma: overview of the North American and European
      experience.
AB  - MPM is an uncommon disease with limited treatment options. Early diagnosis, a
      standardized staging system, early referral to centers experienced in MPM, and
      efforts to develop collaborative multicenter trials are essential to improving
      treatment for patients with MPM. Efforts to manage this malignancy, which is
      projected to peak in the twenty-first century, constitute an important
      international health concern, particularly because the use of asbestos, despite
      successful regulatory efforts in many parts of the world, continues unabated in
      others.

PMID- 15559051
TI  - Pathology of mesothelioma.
AB  - In this article, progress in distinguishing mesothelioma from mesothelial
      hyperplasia and fibrosing pleuritis was discussed. Advances in the
      immunohistochemical characterization of mesothelioma, in the recognition of
      entities that mimic mesothelioma, and in their distinction from mesothelioma were
      reviewed. Cytogenetic and molecular genetic contributions to the diagnosis of
      pleural synovial sarcoma were briefly summarized. The diagnosis of epithelial
      type mesothelioma can be established in most cases. Several mesotheliomas,
      however, especially rare subtypes, and sarcomatoid, desmoplastic, and poorly
      differentiated mesotheliomas continue to present diagnostic challenges.

PMID- 15559052
TI  - Genetics of malignant pleural mesothelioma: molecular markers and biologic
      targets.
AB  - MPM is a poorly understood lethal malignancy. Although the pathobiology of MPM is
      not completely elucidated, new genomic technology is likely to help shed light on
      the mechanisms of carcinogenesis through genome-wide screening of tumor-specific
      gene expression. Related efforts to identify the molecular markers of
      mesothelioma are pursued with the aim of refining current diagnostic
      capabilities, predicting prognosis, and designing appropriate trimodality
      programs. These new genomic tools also will assist efforts to tailor current
      adjuvant and neoadjuvant therapies, optimizing their effect and furthering
      research that may lead to new therapeutic options.

PMID- 15559053
TI  - Epidemiology, biologic behavior, and natural history of mesothelioma.
AB  - Malignant pleural mesothelioma has a well described natural history but poorly
      defined pathogenesis. It is strongly associated with asbestos exposure. A
      predominantly locally invasive disease, the success of more aggressive life
      prolonging therapies has increased the potential for the development of distant
      metastases in survivors. Recently described new risk factors may increase the
      incidence of this disease in future generations, underscoring the need for a more
      in-depth understanding of its pathobiology. This article reviews the current body
      of knowledge about the occurrence, distribution, presentation, and natural
      history of malignant pleural mesothelioma.

PMID- 15559054
TI  - Role of asbestos in etiology of malignant pleural mesothelioma.
AB  - The evidence presented in this article demonstrates that asbestos fibers may be
      genotoxic to mesothelial cells through their distinctive structure and chemistry
      and through their interactions with complex cellular response mechanisms.
      Reactive oxygen and nitrogen species play a key role. Understanding the balance
      between these complex mechanisms that permit neoplastic transformation and
      facilitate the proliferation of tumor cells is the focus of current investigation
      in the development of mesothelial malignancy. In human disease, the persistence
      of asbestos fibers in the lung and pleural tumor is a critical feature that links
      the exposure to asbestos with the development of disease.

PMID- 15559055
TI  - Evidence of an important role for SV40 in mesothelioma.
AB  - The discovery of SV40 DNA in human mesothelioma has evolved from a finding that
      originally was dismissed as polymerase chain reaction contamination to one that
      has won approval for a National Cancer Institute Rapid Access to Intervention
      Development grant to vaccinate SV40-positive tumors with a vaccinia mTag
      construct. As the credibility of these findings has become imprinted in the
      literature, the burden of phenomenon dismissal has become more difficult for
      investigators who have based their arguments on critically flawed validation
      studies. Mesothelioma is a disease for which novel strategies of detection or
      treatment should be encouraged, and it is as dangerous as a hungry shark. In the
      past, the argument always has been whether the finding of SV40 in mesothelioma is
      credible enough to lead our thinking in another direction to help our patients.
      Unfortunately, the causality issues have been stuck to the issue like a remora on
      a shark. It is time to study the remora, but our priorities should be on taming
      the shark.

PMID- 15559056
TI  - Causality of mesothelioma: SV40 question.
AB  - The fragility of the evidence for SV40 association with human cancer is seen in
      studies of NHL. A publication in 1999 stated that SV40 is rarely present in NHL.
      In 2002, two laboratories reported SV40 sequences in 42% to 43% of cases of NHL .
      One of these laboratories also detected SV40 sequences in small proportions of
      pediatric tumors (e.g., Wilm's tumor, hepatoblastoma, rhabdomyosarcoma,
      medulloblastoma, osteosarcoma, and retinoblastoma) and adult carcinomas (e.g.,
      lung, colon, breast, and prostate) These positive results were not confirmed in
      subsequent studies published in 2003. Capello et al and Mackenzie et al failed to
      detect SV40 sequences in NHL tissues. Sanjose et al examined sera from patients
      with NHL and from controls for antibodies reactive to SV40 VLPs, and they
      detected no significant differences between the two groups. The association of
      SV40 with NHL is in doubt. An etiologic link between a virus and a cancer becomes
      plausible when evidence from different lines of enquiry (e.g., epidemiology,
      pathogenesis, and molecular mechanisms) is mutually reinforcing and together
      provides a coherent picture that can connect the biology the virus to the
      characteristics of the disease. The associations of human papillomaviruses with
      cervical cancer and hepatitis B and C viruses with hepatocellular carcinoma are
      examples in which the etiologic link is clear. With SV40 and mesothelioma, the
      data on viral sequences in tumors is inconsistent and disputed, and serologic
      evidence does not support any association. The epidemiologic data do not show
      that documented exposures tt SV40 increase the risk of mesothelioma. It seems
      improbable that a single virus (which cannot be conclusively demonstrated to be
      present in the community) contributes to the development of such a wide variety
      of tumors, spanning all age groups and histologic types. The weaknesses in the
      evidence linking SV40 with mesothelioma are summarized in Box 11 It seems
      unlikely that infection with SV40 contributes to the development of human
      mesothelioma or any other human cancer.

PMID- 15559057
TI  - Preoperative assessment and therapeutic options for patients with malignant
      pleural mesothelioma.
AB  - Prompt medical evaluation and aggressive treatment can lead to prolonged survival
      or successful palliation of symptoms for patients with malignant pleural
      mesothelioma, but the window for implementing treatment is short. Clinical
      recognition of the cancer is confounded by numerous factors, including long
      latency between exposure to asbestos and expression of the disease, nonspecific
      nature of the presenting symptoms, rarity of the disease, a lack of experience in
      clinical diagnosis, and rapidly deteriorating clinical course after diagnosis.
      Heightened clinical suspicion and proper patient selection through accurate
      staging and pathologic identification are paramount to defining and delivering
      therapy for this rare, lethal cancer.

PMID- 15559058
TI  - Pleurectomy and decortication for malignant mesothelioma.
AB  - P/D in combination with other therapies remains an effective weapon in the
      thoracic surgeon's armamentarium for treating patients with MPM, particularly
      patients with limited lung function. A clear benefit has been demonstrated in
      terms of symptom relief. Further strategies aimed at eliminating residual disease
      in an effort to prevent locoregional recurrence and as potential curative
      therapies currently are being investigated.

PMID- 15559059
TI  - Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma: techniques
      and complications.
AB  - Innovative therapeutic agents and strategies are being investigated to improve
      survival with this lethal disease. New chemotherapy agents, including gemcitabine
      (Eli Lilly and Company; Indianapolis, Indiana) and pemtrexed (Eli Lilly and
      Company) show promise against mesothelioma. Kaiser has reported using novel
      therapies, such as cytokines and suicide gene therapy, to target mesothelioma.
      Pass et al , Moskal et al , Schouwink et al , and Friedberg et al have applied
      photodynamic therapy to the hemithorax after surgical resection. Because
      recurrence of mesothelioma after surgical resections tends be locoregional rather
      than distant , strategies to improve local control may be beneficial. Several
      groups, including our Brigham and Women's Hospital Thoracic Surgery Division and
      Dana Farber Thoracic Oncology Program, are investigating intraoperative
      intracavitary lavage of hyperthermic chemotherapy immediately after EP (discussed
      elsewhere in this issue). Although mesothelioma remains a difficult disease to
      treat, the techniques of surgical resection for mesothelioma have improved
      dramatically. Currently, EPP can be performed with acceptable morbidity and
      mortality at experienced centers.

PMID- 15559060
TI  - Multimodality therapy in mesothelioma: role of chemotherapy.
AB  - The few long-term survivors of MPM have been cured with radical surgical
      extirpation often followed by radiation therapy and adjuvant chemotherapy. The
      combination of pemetrexed and cisplatin recently was shown to improve survival
      over treatment with cisplatin alone. Given the size and robustness of that trial,
      the combination should be the new standard treatment for this cancer. Combined
      modality approaches to therapy, including surgery, radiation, and chemotherapy,
      are becoming the standard of care in patients with resectable mesothelioma. Two
      phase II studies have demonstrated that neoadjuvant chemotherapy is safe and
      apparently effective. A third phase II trial will use the combination of
      pemetrexed plus cisplatin preoperatively followed by surgery and radiation for
      patients with T1-3 N0-2 mesothelioma. If the statistical analysis of this study
      shows a measurable pathologic complete response rate and a median survival that
      exceeds the current expected value of 20 to 24 months, a phase III trial
      comparing surgery and radiation to surgery, radiation, and chemotherapy will be
      considered.

PMID- 15559061
TI  - External beam radiation therapy for the treatment of pleural mesothelioma.
AB  - Technical challenges in the treatment of pleural mesothelioma with radiotherapy
      remain. When there is limited or no resection of disease, delivery of high-dose
      RT to the entire hemithorax in the setting of an intact lung has not been shown
      to be associated with any survival benefit, and the toxicity is clearly
      significant. Conversely, the use of palliative RT delivered to limited fields
      (less than hemithorax) can provide pain relief in 50% to 70% of cases. After
      pleurectomy and decortication, delivery of a tumoricidal dose of radiation to
      potential microscopic mesothelioma is similarly problematic. Details of various
      sophisticated radiation techniques, such as photon and electron matching,
      intraoperative RT, and the use of multiple small treatment beams using IMRT, have
      been published, and the former two techniques have been used. Although these
      approaches are innovative and creative, they have significant limitations in
      terms of the total dose that can be delivered, dose homogeneity, and the ability
      to cover fully all the areas at risk (e.g., fissures). Finally, implementation of
      RT after EPP permits delivery of higher doses than in the post-pleurectomy
      setting using treatment techniques such as photon/electron matching and IMRT. The
      dosimetry remains limited by the surrounding normal structures (heart and liver,
      particularly). Studies have shown that it is feasible to deliver nominal doses of
      50 to 54 Gy after EPP, and local control rates have improved . Although the
      target volumes may not be covered fully by these doses, it is a significant
      improvement over lower dose treatment plans. In the future, it is reasonable to
      continue to pursue aggressive surgical resection with EPP and further refine
      these complex radiotherapy techniques. Treatment with novel agents, such as
      alimta, in the neoadjuvant setting also may further enhance local and systemic
      control of pleural mesothelioma.

PMID- 15559062
TI  - Innovative therapies: intraoperative intracavitary chemotherapy.
AB  - Both phase I studies demonstrated that high-dose cisplatin can be delivered
      safely with acceptable complication rates. The maximum tolerated doses of 225
      mg/m2 and 250 mg/m2 cisplatin, respectively, are higher than any other published
      report of intrapleural cisplatin. The intrapleural cisplatin doses reported in
      other trials have been 80 mg/m2, 100 mg/m2, and 200 mg/m2. Despite the use of
      high-dose intraoperative chemotherapy, the group of 50 patients who underwent EPP
      experienced mortality and morbidity comparable to the contemporaneous group of 41
      patients who did not participate in the protocol, except for increased rates of
      deep venous thrombosis and diaphragmatic patch failure. The 44 patients who
      underwent P/D experienced a slightly higher mortality rate and creatinine
      toxicity rate than the first phase I trial. Given the demographics of this
      patient cohort (higher age, lower FEV1, and inability to withstand pneumonectomy
      because of limited cardiopulmonary reserve), however, the mortality and morbidity
      rates seem acceptable. The pharmacologic data from both studies support our
      hypothesis that high regional doses of cisplatin can be delivered with less
      systemic absorption than can be achieved with intravenous administration (data
      not shown). With the maximum tolerated dose of intracavitary cisplatin and safety
      of intraoperative administration after surgical resection firmly established by
      these phase I trials, we are prepared to implement phase II and III studies of
      EPP and P/D with intraoperative cisplatin lavage. We aim to monitor tumor
      recurrence and patient survival prospectively and compare these results with
      historic controls. We also intend to document prospectively the morbidity and
      mortality of the treatment protocols. Finally, we plan to evaluate the
      pharmacokinetics of cisplatin by measuring tissue and perfusate levels of active
      and inactive cisplatin. By approaching the problem of local recurrence after
      resection of MPM in a careful and methodical manner, we hope to decrease or delay
      the rate of recurrence and potentially improve longterm survival in patients with
      this lethal disease.

PMID- 15559063
TI  - Innovative therapies: photodynamic therapy.
AB  - Photodynamic diagnosis could be a useful tool for improving the diagnostic yield
      of tumor biopsy, especially for mesothelioma tumors that are sclerotic and
      particularly hypocellular. For PDD, the use of low doses of a sensitizing drug,
      such as 5-ALA, must be investigated further. The initial results of 5-ALA
      mediated PDD are promising. The role, if any, for PDT in the treatment of
      mesothelioma has yet to be established. The number of centers exploring this
      technology is limited because the procedure is labor intensive and requires not
      only specialized equipment but also physician support. The number of patients
      treated in the different trials is small, and no definitive conclusions can be
      drawn. Further complicating the interpretation of published results is the number
      of variables (i.e., type of sensitizer, light dose, drug dose, drug light
      interval, methods of light measurement, technique of light delivery, surgical
      debulking techniques), which differ between studies. Most reports are phase I and
      II studies. The final outcome of these studies with respect to survival is of
      limited value. The only phase III study, which was performed with an earlier
      generation photosensitizer, reported no advantage to the use of PDT in
      combination with surgery and immunochemotherapy. To date, the most that can be
      said is that intraoperative PDT can be performed safely in experienced centers
      and that there are some encouraging results, especially in patients with stages I
      and II MPM, particularly with the newer generation photosensitizers. One
      attractive aspect of this adjuvant treatment is that PDT, as opposed to some of
      the other adjuvant treatments combined with surgery, may offer the option of
      effecting adequate tumor debulking with a pulmonary-sparing procedure.

PMID- 15559064
TI  - Patterns of failure following surgical resection for malignant pleural
      mesothelioma.
AB  - The optimum therapeutic strategy for patients with localized malignant
      mesothelioma continues to evolve. For patients who are eligible candidates,
      surgical resection plays an important role. An encouraging 45% 5-year survival
      rate has been reported for patients with early-stage disease who undergo EPP and
      have the favorable features of epithelial histology and the absence of
      mediastinal lymph node involvement. Most patients present with more advanced
      disease, however, and the optimum local and systemic treatment for these patients
      has not been defined. No randomized trials evaluating the various surgical or
      adjuvant therapeutic approaches have been performed. Evaluation of treatment
      efficacy based on observed patterns of failure may suffer from treatment
      selection biases. Most studies also do not separate out the failure patterns
      based on the initial stage (clinical or pathologic) of the disease. Consequently,
      it is difficult to discern the potential impact of a given adjuvant therapy.
      Given these limitations, however, some consistent observations from the available
      data can be made. For patients who undergo P/D, local recurrence (within the
      surgically operated hemithorax) is the most common form of recurrence. Efforts to
      decrease the chance of local recurrence after P/D have included the use of
      intrapleural and intravenous chemotherapy, brachytherapy, and external beam
      radiation therapy. None of these adjuvant treatment trials was randomized, and
      when compared with historical controls, none of the treatments used suggested a
      consistent outcome benefit. After P/D, the use of radiation is limited by the
      potential toxicity of the underlying organs, most importantly, the intact lung.
      Doses required to treat mesothelioma effectively are above the doses that would
      lead to damage to the lung parenchyma. Cisplatin and mitomycin have been used as
      agents have modest activity against mesothelioma. The doses of cisplatin used may
      not have been optimal, although they were based on prior pharmacokinetic studies.
      Alternative approaches for patients who undergo P/D, such as the use of
      escalating doses of heated intrapleural cisplatin (given with a renal protecting
      agent, sodium thiosulfate, which provides the opportunity to deliver higher doses
      of chemotherapy), are being pursued by Sugarbaker et al. The availability of more
      active systemic chemotherapy agents or other intrapleural agents also may offer
      better therapeutic options for patients who undergo P/D. Recently, Vogelzang et
      al presented the findings of a large randomized study that compared
      cisplatin/premetrexed to cisplatin and demonstrated an improvement in response
      rate (41% for cisplatin/pemetrexed versus 19% for cisplatin) and median survival
      (12.1 versus 9.3 months, respectively; P = 0.020). Other chemotherapy regimens
      with encouraging activity in mesothelioma include the combination of cisplatin
      and gemcitabine, with response rates ranging from 16% to 48%. From a review of
      available data, patients with mesothelioma who have undergone P/D (with or
      without intrapleural chemotherapy) who are evaluated at the Dana Farber Cancer
      Institute and Brigham and Women's Hospital are offered therapy with systemic
      chemotherapy alone. After P/D, radiation is used only for palliative treatment.
      Patients who have undergone P/D are also appropriate candidates to receive
      chemotherapy or other novel therapeutic strategies being evaluated in clinical
      trials. For patients who have undergone EPP, the pattern of recurrence is
      predominantly a combination of local and distant failure (Table 1). The local
      recurrence rates, however, seem to be lower than rates seen after P/D. This
      observation may represent a shift of the natural history of the disease.
      Metastatic mesothelioma is often seen late in the course of the disease, but it
      may become the dominant source of disease after aggressive local surgical
      management. Many studies define abdominal recurrence as a site of distant
      recurrence, although this may represent transdiaphragmatic extension of the
      pleural mesothelioma. Advances in local therapy also may decrease the rate of
      abdominal recurrences. True distant recurrences (bone, central nervous system,
      contralateral hemithorax) remain less common. The lowest rate of local recurrence
      (13%), with a 4% local-only recurrence rate, was seen in the study by Rusch et
      al, who used 54 Gy hemithorax radiation as adjuvant therapy. This is the lowest
      rate of local recurrence after an EPP that has been reported. Baldini et al
      reported a 50% local recurrence rate, with a 13% local-only rate, after
      trimodality therapy. One possibility for the differences between these two
      reports is the lower dose of radiation (30.6 Gy) used in the latter study. In the
      study by Rusch et al, distant failures predominate, and the patients are
      appropriate candidates for systemic chemotherapy, which could be administered
      either as neoadjuvant or adjuvant therapy. Kestenholz et al currently are
      performing a phase II clinical trial of neoadjuvant cisplatin and gemcitabine
      administered for three cycles followed by EPP and adjuvant radiation therapy. A
      similar approach also is being pursued in an ongoing clinical trial using
      neoadjuvant cisplatin/pemetrexed for four cycles before EPP followed by 54 Gy of
      adjuvant hemithorax radiation. Alternatively, patients who have undergone EPP
      could be treated with adjuvant chemotherapy in addition to adjuvant radiation
      therapy. Currently, patients evaluated at the Dana Farber Cancer Institute and
      Brigham and Women's Hospital who have undergone EPP are offered adjuvant
      chemotherapy followed by hemithorax radiation to 54 Gy in an effort to maximize
      local and distant control rates. Further clinical studies are needed for all
      patients with mesothelioma to define the optimum surgery and duration and types
      of adjuvant therapy. The appropriate multimodality approaches most likely will
      differ based on disease stage, histology, and patient performance status.
      intrapleural chemotheraphy treatments. These two For Patients who have undergone
      EPP, the pattern

PMID- 15559065
TI  - Anesthetic strategies for patients undergoing extrapleural pneumonectomy.
AB  - Anesthetic management of patients with extrapleural pneumonectomy may contribute
      to risk reduction, and it differs from management of patients with standard
      pneumonectomy in several respects. Hemodynamic and intravascular fluid management
      is complicated by the significantly greater blood loss and impairments of venous
      return imposed by weighty tumors and the blunt dissection process. There are
      greater risks of catastrophic (central) bleeding, dysrhythmias, cardiac
      herniation, and electrocardiographic changes. Restrictive forces increase the
      likelihood of dependent lung atelectasis during single-lung ventilation.
      Preoperative assessment of cardiopulmonary reserve remains an imprecise process.
      Awareness of these risks and limitations enables the anesthesiologist to
      understand, anticipate, and potentially preempt many intraoperative problems.

PMID- 15559066
TI  - Pain management strategies for patients undergoing extrapleural pneumonectomy.
AB  - The role of anesthetic or analgesic technique in outcome remains controversial.
      The choice of anesthetic and postoperative analgesic plan plays a small, albeit
      important, role in perioperative care and a multimodal rehabilitation program.
      Pulmonary complications are the most important cause of morbidity and mortality
      after EPP. There is increasing evidence that TEA with local anesthetic agents and
      opioids is superior for the control of dynamic pain, plays a key role in early
      extubation and mobilization, reduces postoperative pulmonary complications, and
      has the potential to decrease the incidence of PTPS.

PMID- 15559067
TI  - A profile of hospital union election activity, 1985--1994 NLRB rulemaking and
      results in right-to-work states.
AB  - The authors present union election results in non-governmental, short-term
      hospitals for the 10-year period 1985--1994. The authors include profiles for the
      periods before (1985--1989) and after (1990--1994) the National Labor Relations
      Board (NLRB) rulemaking. When comparing the period data, they found that the
      impact of rulemaking was a reduction in mean bargaining unit size, an increase in
      the absolute number of elections in hospitals, and an increase in the percentage
      of union wins. Their examination of hospital union election results in right-to
      work (RTW) versus non-RTW states revealed that unions did not aggressively try to
      organize workers in non-RTW states and, when they did, they were not very
      successful. When the authors examined only initial recognition elections during
      the periods before and after rulemaking, as well as the whole 10 years,
      regression analysis identified three variables significantly related to union
      wins: the 1989 NLRB rule change, bargaining unit size, and employee participation
      rates.

PMID- 15559068
TI  - Machiavelli's advice to the hospital chief executive officer.
AB  - Hospital chief executive oficers (CEOs) have demanding jobs in which they must,
      at tims, function as if they are potentates of small principalities. Their
      ability to elicit loyalty and allegiance, hand out discipline and praise, foster
      alliances with other organizations, and commit the occasional hostile yet (it is
      hoped) successful foray onto a competitor's turf are skills that must be mastered
      for success and longevity. We have taken the thoughts and strategies of the
      Renaissance political master, Niccolo Machiavelli, and applied them to the modern
      hospital CEO for whom we feel they still hold elements of wisdom and guidance.

PMID- 15559069
TI  - Managerial socialization in short-term hospitals: some early evidence.
AB  - In contrast to business corporations, little has been written about early
      managerial behavior in short-term, general hospitals. An executive transition
      into a new organization presents both risk and opportunity. This exploratory
      study into managerial socialization is aimed at identifying what healthcare
      executives actually do during the transition period from onset of recruitment to
      the end of their first 6 months in a new hospital position. The findings of this
      research should be useful in helping CEOs to plan for their transition into short
      term, general hospitals. For these top management executives, the stakes are very
      high. In many instances, CEOs are expected to change the way their hospitals
      work. An understanding of the strategic, tactical, political, and cultural
      approaches they have used should help lead to more successful transition outcomes
      and effective organizational change.

PMID- 15559070
TI  - Terri Schindler Schiavo: an update.

PMID- 15559071
TI  - Employers' roles in effectively and efficiently handling workers' compensation
      issues.

PMID- 15559072
TI  - The usefulness of the brainstem auditory evoked potential in the early diagnosis
      of cranial nerve neuropathy associated with diabetes mellitus.
AB  - BACKGROUND: An evaluation of the extent and mechanism of damage of the central
      nervous system in diabetes mellitus is of high value in current neurological
      research. Electrophysiological abnormalities are frequently present is completely
      asymatomatic diabetes mellitus (DM) patients. Limited data is available in the
      use of brainstem auditory evoked potential (BAEP) in DM. AIM: Is to evaluate the
      efficacy of BAEP as a method useful in the diagnosis of subclinical damage of the
      central nervous system in DM. MATERIAL AND METHOD: 67 diabetes and 32 healthy
      controls - age and sex matched - were chosen. The diabetes were of type I and II
      and more than or less than 10 years duration. The BAEP was elicited by using
      auditory stimulus by using Dantec Evomatic 4000 evoked potential machine. The
      latency of component response recored as waves I, III and V, interpeak latency
      (IPLs) I - III, I - V, III - V and amplitude of waves V. RESULTS: The difference
      was highly significant in the increased latency of waves I, III and V, interpeak
      latency (IPLs) I - III, I - V, III - V and amplitude of waves V of each type of
      diabetes as compared to control. Comparison of the type and duration of diabetes
      between each other showed no significant difference. CONCLUSION: BAEP recording
      can represent an objective, clinically useful and non invasive procedure to
      stress the early impairment both of the auditory nerve and of brainstem function.

PMID- 15559073
TI  - Differential presence of fibrillation in mimic muscles in Bell's palsy.
AB  - The presence of fibrillation in mimic muscles in Bell's palsy was investigated
      during a clinical and electrophysiological follow-up study. Fibrillation was
      present in 58,82% of the frontalis and mentalis, but only in 29,41% of the
      orbicularis oculi (OO) muscles tested. Furthermore, the amount and the time
      course of fibrillation were also different, without any significant differences
      concerning the EMG pattern among the three muscles. The compound muscle action
      potential (CMAP) of the OO was negatively correlated with the presence of
      fibrillation. The recovery of OO was slightly better than that of the others
      muscles. An attempt of interpretation of these findings is made on the line of a
      possible sparing of the OO nerve fibers and the unique histochemical properties
      of the OO. On these grounds, fibrillation in the OO in Bell's palsy is less
      frequent than as in the other mimic muscles, and its absence is not necessarily
      indicating a good prognosis.

PMID- 15559074
TI  - Assessing information of soleous and gastrocnemius motor unit H-reflex response
      to paired stimulation.
AB  - In this study we compared soleous and gastrocnemius muscles responses to paired
      stimulation in order to reveal the embedded information in H-reflex of these
      muscles. Four men with ages between 20 and 26 were tested. Since there was no
      ideal point based on the scientific rules to record H-reflex from gastrocnemius
      muscle, we were to determine an ideal point and electrode placement from
      anatomical and physiological point of view. Then, soleous and gastrocnemius
      muscles were subjected to paired stimulus and H-reflex recovery curve of these
      muscles were recorded To record the recovery curve, 11 pairs of stimulus were
      delivered to the posterior tibial nerve. Time interval between the 1st pair of
      stimulus was 50 ms and increased by 20 ms steps in the next pairs up to 250 ms.
      The second H-reflex amplitude was divided to the first H-reflex amplitude and
      expressed in percent, then the recovery curve was drawn accordingly. While the
      time interval of the paired stimulus was less than 110 ms, the behavior of the
      curves was similar. In this stage we guessed that the muscles were impressed by
      the renshaw cells inhibition and the induced fatigue by the first stimulus. When
      the interval in a pair was 110 ms or more, the recovery percent of soleous was
      significantly higher than that of the gastrocnemius. This behavior may be due to
      the less fatigability of soleous motoneurons and less renshaw inhibition on slow
      motoneurons of soleous. When the time interval of a pair stimulus increases to
      more than 170 ms, both of the curves behave alike. This may be due to the
      diminishing of renshaw cell inhibition and the reduction of fatigue. Because of
      motoneurons physiological properties, when we evoke H-reflex, smaller motoneurons
      recruit predominantly; but the comparison of the soleous (slow) and gastrocnemius
      (fast) recovery curves behavior shows that the information about the fast
      motoneuron are included in H-reflex using this procedure. So we can indirectly
      assess different motoneurons and renshaw cell activities.

PMID- 15559075
TI  - Primary orthostatic tremor: analysis of three cases.
AB  - Primary orthostatic tremor (POT) is a rare form of tremor characterized by
      unsteadiness and quivering of lower extremities while standing. These symptoms
      relieve when sitting or reclining It is much less apparent when leaning against
      an object or during walking. The rhythmic tremor activity with a frequency of 13
      18 Hz can be obtained electromyography recordings. Here we report three cases
      that have typical clinical and electrophysiological findings of POT.

PMID- 15559076
TI  - Recurrent inhibition in the soleus motor pool of elderly and young adults.
AB  - Recurrent inhibition in the spinal cord has been suggested to serve as a variable
      gain regulator to allow for optimal muscle force control, to influence alpha
      motoneuron firing rate, and to contribute to task related motor synergies between
      muscles at the same or different joints. The purpose of this study was to examine
      the resting recurrent inhibition levels in the soleus motoneuron pool of 20
      elderly and 21 young adult subjects. To assess recurrent inhibition, a
      conditioning electrical stimulus was used to activate group Ia afferent fibers
      and elicit a reflex response in some of the a-motoneurons innervating the soleus
      muscle; producing both activation of Renshaw interneurons excited by those
      involved soleus a-motoneurons via a recurrent branch of the a-motoneuron axon,
      and an H-reflex response in the soleus muscle. A H' test reflex elicited by a
      successive supramaximal stimulus to the same nerve 10 ms after the conditioning
      stimulus evaluated the resulting inhibitory effect. There was no difference in
      the H' test reflex amplitude when comparing the young and elderly adult subjects.
      This result was found following two different methods employed to control for a
      possible effect on the H' test reflex amplitude of a smaller maximum H-reflex
      amplitude in the elderly subjects. These results indicate that the level of
      recurrent inhibition in the motoneuron pool of the resting soleus muscles of the
      young and elderly adults examined was not significantly different.

PMID- 15559077
TI  - Electrophysiological and clinical assessment of a simple wrist-hand splint for
      patients with chronic spastic hemiparesis secondary to stroke.
AB  - PURPOSE: The aim of this study is to assess the effect of a simple wrist-hand
      splint, made of mesh materials, on the spastic paretic hand. METHODS: The
      participants were 15 patients with hemiparetic stroke. Time from stroke onset was
      over 120 days. We assessed integrated EMG of flexor digitorum sublimus (FDS),
      extensor indicis proprius (EIP), flexor carpi radialis (FCR), extensor carpi
      radialis (ECR), brachioradialis (BR) and triceps brachii (Tri) during active
      finger extension and shoulder flexion, without and with the wrist-hand splint. H
      reflexes and M waves were obtained on FCR by stimulating the median nerve, and
      H/M ratio was calculated. In another 5 patients who used the splint for 8 weeks,
      its long-term effects were assessed with clinical measures (active range of
      motion and muscle tone). RESULTS: With the splint, muscle activities of FCR and
      BR were reduced during shoulder flexion, and those of FDS, FCR and BR decreased
      during finger Attaching the splint also reduced the H/M ratio of FCR. In five
      patients who had worn the wrist-hand splint during daytime for 8 weeks,
      significant increase in the active range of shoulder flexion and finger extension
      and decrease in muscle tone were demonstrated. The splint reduced co-activation
      of antagonists not only in wrist but also in finger and elbow muscles.
      CONCLUSION: It is suggested that the wrist-hand splint is beneficial to improve
      upper limb motor function in patients with spastic hemiparesis.

PMID- 15559078
TI  - Mechanomyographic and electromyographic amplitude and frequency responses during
      fatiguing isokinetic muscle actions of the biceps brachii.
AB  - The purpose of this investigation was to examine the mechanomyographic (MMG) and
      electromyographic (EMG) amplitude and mean power frequency (MPF) patterns during
      fatiguing isokinetic muscle actions of the biceps brachii. Ten adults [three
      women (mean +/- SD age = 20 +/- 2 yrs) and seven men (mean +/- SD age = 23 +/- 3
      yrs) ] volunteered to perform 50 consecutive maximal, concentric isokinetic
      muscle actions of the biceps brachii at 180 degrees x s(-1). The percent decline
      (mean +/- SD) in isokinetic peak torque (PT) was 70 +/- 17% and polynomial
      regression analyses indicated a cubic relationship (R2 = 0.994) between PT and
      repetition number. Both MMG amplitude and MMG MPF decreased linearly (r2 = 0. 774
      and 0.238, respectively) across repetitions. The results for EMG amplitude
      demonstrated a cubic (R2 = 0.707) pattern across repetitions, where EMG amplitude
      increased during repetitions 1-20, remained stable during repetitions 20-40, and
      increased during repetitions 40-50. There was a quadratic (R2 = 0. 939) reduction
      in EMG MPF throughout the test. The decreases in MMG amplitude and MMG MPF may
      have been due to de-recruitment of fast fatiguing motor units, a reduction in
      muscular compliance, or the effects of "muscle wisdom." The results for EMG
      amplitude may have reflected nonmaximal efforts by the subjects and/or peripheral
      fatigue. The factor(s) determining the decrease in EMG MPF are unclear, although
      a reduction in muscle fiber action potential conduction velocity may have been
      partially responsible.

PMID- 15559079
TI  - Effects of acute and chronic denervation on human myotonia.
AB  - A 32-year-old man with myotonia congenita (Becker type) sustained multiple
      gunshot wounds. These produced a partial thoracic spinal cord injury and a severe
      sciatic nerve injury. Six days following the incident, clinical (percussion) and
      electrophysiologic (EMG) myotonia could be elicited in paretic leg muscles
      resulting both from the myelopathy and peripheral nerve disruption. Eight months
      later, the myotonia was no longer present in denervated muscles from the sciatic
      nerve injury, but was still noted in muscles with upper-motor neuron weakness
      from the myelopathy. Although myotonia is related principally to abnormalities in
      the muscle fiber itself, it appears that it is also dependent upon the structural
      integrity of the peripheral nerve supply to the muscle for myotonia to continue
      to occur. The findings in this patient suggest that myotonia may well have
      diminished and disappeared in muscles shortly after the nerves had undergone
      Wallerian degeneration. Myotonia does not recur if there is no significant
      reinnervation.

PMID- 15559080
TI  - The limits of slogans.

PMID- 15559081
TI  - Missed opportunity.

PMID- 15559082
TI  - Staying current.

PMID- 15559083
TI  - Respect versus reverence.

PMID- 15559084
TI  - Restoring humanism.

PMID- 15559085
TI  - Will there be a doctor in the House?

PMID- 15559086
TI  - Politics in the lab.

PMID- 15559087
TI  - Continuing the war on cancer.

PMID- 15559088
TI  - Budget expected to dominate 2005 legislative session.

PMID- 15559089
TI  - Clean air Minneapolis clears smoke.

PMID- 15559090
TI  - MEDPAC makes a difference.

PMID- 15559091
TI  - On call at city hall.

PMID- 15559092
TI  - Playing politics.

PMID- 15559093
TI  - Taming the paper tiger.

PMID- 15559094
TI  - How did a surgeon like me end up in a role like this?

PMID- 15559095
TI  - Dr. Liebow or Mr. Liebling?

PMID- 15559096
TI  - Observations from the Fleet Center.

PMID- 15559097
TI  - Do we have to sacrifice access and quality to cut costs?

PMID- 15559098
TI  - Will program cuts exacerbate our problems?

PMID- 15559099
TI  - Handling dissent.

PMID- 15559100
TI  - Maximum-strength health care.

PMID- 15559101
TI  - Refocused on reform.

PMID- 15559102
TI  - Dealing with medical uncertainty: a physician's perspective.
AB  - Uncertainty in diagnosis is frequently encountered in medical practice and causes
      stress in patients and physicians. Factors contributing to uncertainty include
      biological variability of patients, patient and physician bias, error in test
      interpretation, differing values and opinions of patients and physicians, and
      uncertainty surrounding decision-making. Physicians differ in their ability to
      tolerate uncertainty, and this varying tolerance has been linked with choice of
      specialty, increased test ordering, personal anxiety, increased cost of providing
      medical care, and decreased comfort with geriatric patients and patients with
      psychological problems. We review the current evidence for and effects of
      physician uncertainty in medical practice. Although uncertainty in practice
      cannot be completely eliminated, numerous strategies can be adopted to decrease
      uncertainty and enhance patients' trust. These include applying the best
      available evidence-based information along with observance of core clinical
      practices, including meticulous history taking, excluding worrisome diagnoses,
      and involvement in shared decision-making.

PMID- 15559103
TI  - Give health care top billing.

PMID- 15559104
TI  - Visual search and attention: an overview.
AB  - This special feature issue is devoted to attention and visual search. Attention
      is a central topic in psychology and visual search is both a versatile paradigm
      for the study of visual attention and a topic of study in itself. Visual search
      depends on sensory, perceptual, and cognitive processes. As a result, the search
      paradigm has been used to investigate a diverse range of phenomena. Manipulating
      the search task can vary the demands on attention. In turn, attention modulates
      visual search by selecting and limiting the information available at various
      levels of processing. Focusing on the intersection of attention and search
      provides a relatively structured window into the wide world of attentional
      phenomena. In particular, the effects of divided attention are illustrated by the
      effects of set size (the number of stimuli in a display) and the effects of
      selective attention are illustrated by cueing subsets of stimuli within the
      display. These two phenomena provide the starting point for the articles in this
      special issue. The articles are organized into four general topics to help
      structure the issues of attention and search.

PMID- 15559105
TI  - Effects of set-size and lateral masking in visual search.
AB  - In the present research, the roles of lateral masking and central processing
      limitations in visual search were studied. Two search conditions were used: (1)
      target differed from distractors by presence/absence of a simple feature; (2)
      target differed by relative position of the same components only. The number of
      displayed stimuli (set-size) and the distance between neighbouring stimuli were
      varied as independently as possible in order to measure the effect of both. The
      effect of distance between stimuli (lateral masking) was found to be similar in
      both conditions. The effect of set-size was much larger for relative position
      stimuli. The results support the view that perception of relative position of
      stimulus components is limited mainly by the capacity of central processing.

PMID- 15559106
TI  - Attentional weighting: a possible account of visual field asymmetries in visual
      search?
AB  - Several previous visual search studies measuring reaction times have demonstrated
      scanning biases across the visual field (i.e. a tendency to begin a serial search
      in a particular region of space). In the present study, we measured visual
      discrimination thresholds for a target presented amongst distractors using
      displays that were short enough to greatly reduce the potential for serial (i.e.
      scanning) search. For both a motion and orientation task, subjects' performance
      was significantly better when the target appeared in the inferior, as compared to
      the superior, visual field (no differences were observed between left and right
      visual fields). These findings suggest that subjects may divide attention
      unevenly across the visual field when searching for a target amongst distractors,
      a phenomenon we refer to as 'attentional weighting'. To rule out the possibility
      that these visual field asymmetries were sensory in nature, thresholds were also
      measured for conditions in which subjects' attention was directed to the location
      of the target stimulus, either because it was presented alone in the display or
      because a spatial cue directed subjects' attention to the location of that target
      presented amongst distractors. Under these conditions, visual field asymmetries
      were smaller (or non-existent), suggesting that sensory factors (such as
      crowding) are unlikely to account for our results. In addition, analyses of set
      size effects (obtained by comparing thresholds for a single target vs. the target
      presented amongst distractors) could be accounted for by an unlimited capacity
      model, suggesting that multiple stimuli can be processed simultaneously without
      any limitations at an early stage of sensory processing. Taken together, these
      findings suggest the possible existence of biases in attentional weighting at a
      late stage of processing. The bias appears to favor the inferior visual field,
      which may arise from the fact that there is more ecologically-relevant
      information in this region of space.

PMID- 15559107
TI  - Signal detection theory applied to three visual search tasks--identification,
      yes/no detection and localization.
AB  - Adding distracters to a display impairs performance on visual tasks (i.e. the set
      size effect). While keeping the display characteristics constant, we investigated
      this effect in three tasks: 2 target identification, yes-no detection with 2
      targets, and 8-alternative localization. A Signal Detection Theory (SDT) model,
      tailored for each task, accounts for the set-size effects observed in
      identification and localization tasks, and slightly under-predicts the set-size
      effect in a detection task. Given that sensitivity varies as a function of
      spatial frequency (SF), we measured performance in each of these three tasks in
      neutral and peripheral precue conditions for each of six spatial frequencies (0.5
      12 cpd). For all spatial frequencies tested, performance on the three tasks
      decreased as set size increased in the neutral precue condition, and the
      peripheral precue reduced the effect. Larger set-size effects were observed at
      low SFs in the identification and localization tasks. This effect can be
      described using the SDT model, but was not predicted by it. For each of these
      tasks we also established the extent to which covert attention modulates
      performance across a range of set sizes. A peripheral precue substantially
      diminished the set-size effect and improved performance, even at set size 1.
      These results provide support for distracter exclusion, and suggest that signal
      enhancement may also be a mechanism by which covert attention can impose its
      effect.

PMID- 15559108
TI  - Termination of a visual search with large display size effects.
AB  - The ability to locate an object in the visual field is a collaboration of at
      least three intermingled processes: scanning multiple locations, recognizing the
      object sought (the target), and ending the search in cases when the target is not
      found. In this paper, we focus on the termination rule. Using distribution
      analyses, it is possible to assess the probability of termination conditional on
      the number of locations examined. The results show that on some trials without
      target, the participants carried out more comparisons than there are objects in
      the display; in other conditions, they carried out fewer comparisons than
      objects. Because there were very few errors, the premature stops were not pure
      guesses. We present models to account for these findings. The distributions of
      terminations help determine the slopes of the functions relating response time to
      set size.

PMID- 15559109
TI  - Attentive mechanisms in visual search.
AB  - Selective attention can be employed to a restricted region in space or to
      specific objects. Many properties of this attentional window or spotlight are not
      well understood. In the present study, we examined the question whether the
      putative shape of the attentional spotlight can be determined by endogenous
      cueing within a visual search paradigm. Participants searched for a target among
      distractors, which were arranged within a vertical or horizontal rectangle. The
      shape of this rectangle was cued endogenously in a valid or invalid way. Response
      times (RTs) to correct identification of target orientation were recorded. In
      Experiment 1, the difference between valid and invalid RTs demonstrated that
      cueing resulted in elongated attentional areas. This was true only for a group of
      experienced psychophysical participants, whereas a group of inexperienced
      participants were not able to use cueing in this way. In Experiment 2, the line
      motion illusion was used to examine the spatial properties of the attended area.
      The results confirmed for both experienced and inexperienced participants that
      attention was confined to the cued elongated area only. We present converging
      evidence for an attentional spotlight whose shape can be adjusted flexibly by
      appropriate endogenous cueing.

PMID- 15559110
TI  - The role of highlighting in visual search through maps.
AB  - Two experiments were conducted in which participants performed a vehicle
      dispatching task. The intensity of one information source (vehicles in Experiment
      1, destinations in Experiment 2) was varied to examine the effects of salience
      and discrimination on both searching for and processing the information in a
      cluttered display. Response times were recorded for questions either requiring
      focused attention on or divided attention between the different information
      domains in the map. The results of the present experiments indicate that it is
      possible to declutter a display without erasing any information. By 'lowlighting'
      one information domain and keeping the other domain at a fairly high intensity
      level, dividing attention between the information sources is optimal, as is
      focusing attention on either of the information domains exclusively. These
      results are discussed in conjunction with a computational model of confusion and
      salience which serves to predict search and integration performance in a
      cluttered display with separate domains of information displayed at different
      intensities.

PMID- 15559111
TI  - Effects of colour on preview search: anticipatory and inhibitory biases for
      colour.
AB  - Two experiments are reported examining the effects of colour grouping, colour
      change and target colour foreknowledge under preview search conditions (Watson
      and Humphreys, 1997). In Experiment 1 we manipulated the colour homogeneity of
      the old items at initial presentation, and the colour these items subsequently
      changed into. In all cases participants knew the colour of the target. We found
      that when the old items changed into the same colour as the new search set,
      search performance was affected. In Experiment 2 participants did not know the
      colour of the target. Here we found evidence for a negative colour-based carry
      over effect that slowed search for new targets carrying the colour of the old
      items. This occurred even when the old items changed their original colour and
      the new target was a singleton. Collectively the results suggest an important
      role for both colour grouping and colour-based inhibition in the successful
      rejection of old distractors. The consequence of this, however, is that new
      stimuli that may carry the critical attribute may take longer to detect. We
      discuss the results in relation to prior 'feature-blind' accounts of preview
      effects on visual search.

PMID- 15559112
TI  - Visual search for apparent-length targets is modulated by the Muller-Lyer
      illusion.
AB  - Is apparent object size represented in pre-attentive vision and can it influence
      visual search for size-defined targets in a spatially parallel manner? This
      question was investigated, using the Muller-Lyer illusion. Observers searched for
      a target line that was longer than the distractor lines. Test lines could be
      presented without context arrows (control); be adjoined by obtuse-angle context
      arrows (arrow heads pointing inward), making the lines appear longer; or by acute
      angle arrows (heads pointing outward), making the lines appear shorter. These
      apparent-length modulations were larger for the target than for the distractor
      lines, thereby increasing and, respectively, decreasing the target-distractor
      length contrast. In line with these changes in contrast, target detection was
      found to be expedited by obtuse-angle arrows and impeded by acute-angle arrows,
      independently of the number of elements in the display. This finding provides
      further evidence for the pre-attentive processing of apparent object size.

PMID- 15559113
TI  - Influence of inter-item symmetry in visual search.
AB  - Does visual search involve a serial inspection of individual items (Feature
      Integration Theory) or are items grouped and segregated prior to their
      consideration as a possible target (Attentional Engagement Theory)? For search
      items defined by motion and shape there is strong support for prior grouping
      (Kingstone and Bischof, 1999). The present study tested for grouping based on
      inter-item shape symmetry. Results showed that target-distractor symmetry
      strongly influenced search whereas distractor-distractor symmetry influenced
      search more weakly. This indicates that static shapes are evaluated for
      similarity to one another prior to their explicit identification as 'target' or
      'distractor'. Possible reasons for the unequal contributions of target-distractor
      and distractor-distractor relations are discussed.

PMID- 15559114
TI  - Spatial context and top-down strategies in visual search.
AB  - Marvin M. Chun and Yuhong Jiang (1998) investigated the role of spatial context
      on visual search. They used two display conditions. In the Old Display condition,
      the spatial arrangement of items in the search display was kept constant
      throughout the experiment. In the New Display condition, the spatial arrangement
      of items was always novel from trial to trial. The results showed better
      performance with Old Displays than with New Displays. The authors proposed that
      repeated spatial context help guiding attention to the target location, thus they
      termed this effect Contextual Cueing. We present three attempts to reproduce this
      effect. Experiments 1 and 2 were near exact replications of experiments in Chun
      and Jiang's report, where we failed to obtain Contextual Cueing. Post
      experimental interviews revealed that participants used different search
      strategies when performing the task: an 'active' strategy (an active effort to
      find the target), or a 'passive' strategy (intuitive search). In Experiment 3, we
      manipulated task instructions to bias participants into using active or passive
      strategies. A robust Contextual Cueing Effect was obtained only in the passive
      instruction condition.

PMID- 15559115
TI  - Rapid iconic erasure without masking.
AB  - We report on the erasure of the iconic memory of an array of 12 black letters
      flashed on a continuously- present white field. Erasure is accomplished by
      replacing the 16 ms letter array (frame 1) with a blank white frame for 16 ms
      (frame 2). The letter array returns in frame 3, with from one to six letters
      missing. Report of the missing letters is accurate without the blank white frame
      but is impoverished with it, as if interposing the blank erases the icon. Erasure
      occurs without any obvious luminance masking, 'mud splashes', pattern masking
      (backward, forward, or metacontrast), lateral masking, or masking by object
      substitution. Erasure is greatly decreased if the blank is presented one frame
      earlier or later. We speculate that erasure is due to a rapid reset of the icon
      produced by an informational mis-match.

PMID- 15559116
TI  - Landmarks help guide attention during visual search.
AB  - Using a novel visual search paradigm McCarley et al. (2003) concluded that the
      oculomotor system keeps a history of 3-4 previously attended objects. However,
      their displays were visually sparse, denying participants structural information
      which might be used during normal search. This might have underestimated memory
      capacity. To examine this possibility, we included landmarks in the same search
      paradigm. Previously examined items were re-examined less frequently when
      landmarks were present compared to when they were absent. Results indicate that
      objects in the environment that share no features with search items are used as
      external support to aid memory in guiding visual search.

PMID- 15559117
TI  - Is object search mediated by object-based or image-based representations?
AB  - Recent research suggests that visually specific memory representations for
      previously fixated objects are maintained during scene perception. Here we
      investigate the degree of visual specificity by asking whether the memory
      representations are image-based or object-based. To that end we measured the
      effects of object orientation on the time to search for a familiar object from
      amongst a set of 7 familiar distractors arranged in a circular array. Search
      times were found to depend on the relative orientations of the target object and
      the probe object for both familiar and novel objects. This effect was found to be
      partly an image matching effect but there was also an advantage shown for the
      object's canonical view for familiar objects. Orientation effects were maintained
      even when the target object was specified as having unique or similar shape
      properties relative to the distractors. Participants' eye movements were
      monitored during two of the experiments. Eye movement patterns revealed selection
      for object shape and object orientation during the search process. Our findings
      provide evidence for object representations during search that are detailed and
      share image-based characteristics with more high-level characteristics from
      object memory.

PMID- 15559118
TI  - Varied-mapping conjunction search: evidence for rule-based learning.
AB  - Five experiments were carried out to examine whether top-down processes can aid
      search, even when targets and distractors are variably mapped. Experiments 1a and
      1b determined that effortless VM search can be obtained in Contrast Polarity X
      Orientation and Color X Orientation conjunction search when one feature dimension
      remains consistently mapped across blocks. Experiment 2 showed that efficient VM
      search is possible when both dimensions are variably mapped. In Experiment 3,
      efficient VM search was found when target-distractor reversals occurred on a
      trial-wise basis. Experiments 4 and 5 found that VM search deteriorates when
      target identity is not known prior to display onset. These studies demonstrate
      the role of top-down mechanisms in the development of efficient VM search and
      present several challenges to strength-theoretic views on the mechanisms
      underlying automaticity.

PMID- 15559119
TI  - A brief history of Gamuts in radiology.

PMID- 15559120
TI  - The development and use of a computer-assisted radiological diagnosis system
      (CARDS) incorporated in the Gamuts in radiology 4.0 CD-ROM.

PMID- 15559121
TI  - Privacy and security issues in teleradiology.
AB  - Teleradiology is now well established within healthcare in the USA, but ethico
      legal concepts surrounding this innovation remain unclear. New legislation, the
      Health Insurance Portability and Accountability Act, as well as ethical
      guidelines and common law demonstrate the importance being placed on security of
      electronic data and the protection of patients' personal data. Radiologists need
      to be aware of the security, privacy, and confidentiality issues which relate to
      teleradiology, so that they can safeguard not only their own interests but also
      the best interests of their patients.

PMID- 15559122
TI  - Artificial neural networks and image interpretation: a ghost in the machine.
AB  - The artificial neural network (ANN) is a non-algorithmic parallel processing
      device modeled after human cerebral architecture. ANNs can be readily simulated
      on a digital computer and have the potential for significant diagnostic
      application in both image- and non-imagebased medical diagnosis. This paper
      briefly discusses the operation of ANNs, differences between these and more
      traditional problem solving methods, and some diagnostic imaging problems
      amenable to their application.

PMID- 15559123
TI  - Overview on research and development of computer-aided diagnostic schemes.
AB  - Computer-aided diagnosis (CAD) has become a practical clinical approach in
      diagnostic radiology, although at present only in the area of detection of breast
      cancer in mammograms. Current research efforts have been focused on detection and
      classification of images of many different types of lesions in a number of
      organs, obtained with various imaging modalities. It is likely that the present
      results of CAD are only at the tip of the iceberg. Although automated computer
      diagnosis is a concept based on computer algorithms only, CAD is a concept
      established by taking into account equally the roles of physicians and computers.
      The effect of CAD on differential diagnosis has already indicated that the
      performance level is high, and that CAD would be ready for clinical trials and
      commercialization efforts. The presentation of images similar to those of an
      unknown case may be useful as a supplemental tool for CAD in the differential
      diagnosis.

PMID- 15559124
TI  - Computerized analysis of images in the detection and diagnosis of breast cancer.
AB  - Improvements in mammographic acquisition techniques have resulted in making the
      early signs of breast cancer more apparent on mammograms. However, the accuracy
      of the overall mammographic examination depends on both the quality of the
      mammographic images and the ability of the radiologist to interpret those images.
      While mammography is the best screening method for the early detection of breast
      cancer, radiologists do miss lesions on mammograms. Use of output, however, from
      a computerized analysis of an image by a radiologist may help him/her in the
      detection or diagnostic tasks, and potentially improve the overall interpretation
      of breast images and the subsequent patient care. Computer-aided detection and
      diagnosis (CAD) involves the application of computer technology to the process of
      medical image interpretation. CAD can be defined as a diagnosis made by a
      radiologist, who uses the output from a computerized analysis of medical images
      as a "second opinion" in detecting and diagnosing lesions, with the final
      diagnosis being made by the radiologist. The computer output must be at a
      sufficient performance level, and in addition, the output must be displayed in a
      user-friendly format for effective and efficient use by the radiologist. This
      chapter reviews CAD in breast cancer detection and diagnosis, including examples
      of image analyses, multi-modality approaches (i.e., special-view diagnostic
      mammography, ultrasound, and MRI), and means of communicating the computer output
      to the human.

PMID- 15559125
TI  - Computer-aided diagnosis for CT colonography.
AB  - CT colonography, or virtual colonoscopy, is a promising alternative screening
      tool for colon cancer. Computer-aided diagnosis (CAD) for CT colonography has the
      potential to increase radiologists' diagnostic performance in the detection of
      polyps and to reduce variability of the diagnostic accuracy among readers.
      Technical developments have advanced CAD for CT colonography substantially during
      the last several years. This paper describes the key techniques used for CAD for
      detection of polyps and masses in CT colonography, the current detection
      performance, and challenges and the future of CAD.

PMID- 15559126
TI  - Computer-aided diagnosis in chest radiology.
AB  - Chest radiography is still a useful examination in various situations, although
      CT has become a modality of choice as a diagnostic examination in many cases.
      Current computer-aided diagnosis (CAD) schemes for chest radiographs include
      nodule detection, interstitial disease detection, temporal subtraction,
      differential diagnosis of interstitial disease, and distinction between benign
      and malignant pulmonary nodules. All of these schemes are demonstrated as
      providing potentially useful tools for radiologists when the output of these
      schemes is used as a "second opinion." There are some commercially available
      products for these schemes and more are expected to be available in the near
      future. The current status of CAD for CT is also discussed briefly in this
      article.

PMID- 15559127
TI  - [Analysis of 15-lipoxygenase activity in irradiated thymocytes].
AB  - We studied the effect of gamma-radiation on 15-lipoxygenase activity in rat
      thymocytes. The enzyme activity was determined as the rate of linoleic acid
      oxidation by the protein fraction isolated from the control and irradiated
      thymocytes under standard conditions. We demonstrate lipoxygenase activation
      immediately after irradiation of thymocytes. High lipoxygenase activity is
      observed in the cells for no more than an hour after irradiation. No high
      lipoxygenase activity later indicates that its synthesis is not directly induced
      by irradiation. Irradiation-induced generation of lipid peroxides can be the
      factor of lipoxygenase activation.

PMID- 15559128
TI  - [Analysis of the expression pattern of regulatory genes Pax6, Prox1, and Six3
      during regeneration of eye structures in the newt].
AB  - We studied tissue-specific expression of homeobox genes Pax6, Prox1, and Six3
      during regeneration of the retina and lens. In the native retina, mRNA of Pax6,
      Prox1, and Six3 was predominantly localized in ganglion cells and in the inner
      nuclear layer of the retina. Active Pax6, Prox1, and Six3 expression was detected
      at early stages of regeneration in all proliferating neuroblasts forming the
      retinal primordium. Low levels of Pax6, Prox1, and Six3 mRNA were revealed in
      depigmented cells of the pigment epithelium as compared to the proliferating
      neuroblasts. At the intermediate stage of retinal regeneration, the distribution
      of Pax6, Prox1, and Six3 mRNA was diffuse and even all over the primordium.
      During differentiation of the cellular layers in the course of retinal
      regeneration, Pax6, Prox1, and Six3 mRNA was predominantly localized in ganglion
      cells and in the inner part of the inner nuclear layer, which was similar to the
      native retina. An increased expression was revealed in the peripheral regenerated
      retina where multipotent cells were localized. The dual role of regulatory genes
      Pax6, Prox1, and Six3 during regeneration of eye structures has been revealed;
      these genes controlled cell proliferation and subsequent differentiation of
      ganglion, amacrine, and horizontal cells. High hybridization signal of all
      studied genes was revealed in actively proliferating epithelial cells of the
      native and regenerating lens, while the corneal epithelium demonstrated a lower
      signal. Pax6 and Prox1 expression was also revealed in single choroid cells of
      the regenerating eye.

PMID- 15559129
TI  - [The dynamics of abscisic acid and cytokinins content in the leaves of wheat
      aegilops lines and their parental forms affected by powdery mildew].
AB  - We studied the dynamics of abscisic acid and cytokinins content in wheat-aegilops
      lines and their parental forms affected by powdery mildew. Lines 95/99i and
      56/99i demonstrated the types of resistance untypical of the soft wheat Rodina
      and Aegilops speltoides k-389 but typical of Ae. speltoides Tausch from other
      natural habitats. A relative stability of the hormonal balance in the course of
      the infection was demonstrated for lines 95/99i and Ae. speltoides k-389 highly
      resistant to the pathogen penetration. Line 56/99i was sensitive to the
      penetration; however, a subsequent prolonged hypersensitive response eliminated
      pathogen colonies surrounded by necrotic areas. A correlation between disbalanced
      hormonal metabolism of cytokinins and low resistance to the infection has been
      revealed for 56/99i line and Rodina cultivar. Free form of abscisic acid was
      revealed in the intact plants of the parental forms. Bound form of this hormone
      was revealed in the infected plants of lines 95/99i and 56/99i as well as of Ae.
      speltoides k-389, which seems to be a marker of their different stress resistance
      according to the phenotypic manifestation of powdery mildew.

PMID- 15559130
TI  - [Changes in parameters of Ascophyllum nodosum dark respiration induced by
      different salinities].
AB  - The changes in the rates of O2 consumption and CO2 release by Ascophyllum nodosum
      thalli in the dark were studied during a 12 day incubation at 34, 20, and 10/1000
      salinity as well as at different pH. Depending on the initial pH of the medium,
      the algae demonstrated antipodal functional responses to the same salinities and,
      as a consequence, different capacity to overcome hypoosmotic stress. In addition,
      we observed a more pronounced effect of pH on the rate of O2 consumption than on
      the rate of CO2 release. Simultaneous desalination and acidification of the
      medium (pH 7-8) increased O2 consumption in the dark, which activated oxidative
      processes in the cells and increased their energy status. Forced pH stabilization
      (8.2) of the medium coupled with its desalination inhibited dark respiration of
      the algae, which, in our opinion, decreased their energy status. Specific
      manifestation of hypoosmotic stress and adaptation in A. nodosum are discussed
      considering the assumed differences in algal energy status.

PMID- 15559131
TI  - [Remote assay for chlorophyll photosynthetic potential of crops on the example of
      wheat].
AB  - An optical remote assay for biological production of crops in the field during
      the vegetation period is proposed. Our calculations demonstrate a good
      correlation between the S(t) value and crop yield (in the range from 0.85 to
      0.90); the higher is S(t) for the vegetation period, the higher is the crop
      yield. S(t) value can be used to calculate the increase in dry and wet biomass
      for various crops during the whole vegetation period with an error of less than
      10-12%. The absolute error of crop yield for 110 cultivars of wheat, oats, and
      barley during the experimental period was +/-3-3.5 quintal/ha with the mean crop
      yield of 14-38 quintal/ha.

PMID- 15559132
TI  - [Effect of deficiency of dietary nitrogen on cellulose digestibility and nitrogen
      fixing flora activity in the sibling vole Microtus rossiaemeridionalis].
AB  - The effect of food composition on nitrogen-fixing activity of the symbionts
      living in the digestive tract of the sibling vole Microtus rossiaemeridionalis
      was experimentally studied. In the control, the rodents were allowed to select
      any of three food mixes: protein-rich, protein-free with low cellulose content,
      and protein-free with high cellulose content. The voles consumed the food in a
      proportion corresponding to 16% of protein and about 6% of cellulose. Exclusion
      of the protein-rich food considerably increased cellulose consumption (up to 12%)
      and digestibility (from 35 to 64%). The changes in the consumed food composition
      were reflected in localization of nitrogenase activity in the digestive tract:
      the control level of nitrogen-fixing activity in the cecum was three times that
      in the proventriculus, while an inverse proportion was observed in the
      experimental groups. In all cases, the colon was the major locus of nitrogen
      fixation.

PMID- 15559133
TI  - [Acoustic image of common rosefinch Carpodacus erythrinus (Pall.)].
AB  - Acoustic analysis of the species-specific call of common rosefinch Carpodacus
      erythrinus was carried out. We compared calls of 12 individuals from the same
      habitat. The individual-specific elements were revealed in the calls. At the same
      time, species-specific elements were also recognized in all individuals. These
      elements compose the acoustic image of common rosefinch call including four
      syllables with intervals.

PMID- 15559134
TI  - [Age-related changes in oxygen consumption in the common mussel Mytilus edulis
      from the White Sea].
AB  - We determined the rate of oxygen consumption in the White Sea mussel Mytilus
      edulis of different ages. The rate of oxygen consumption proved to decrease with
      mussel age according to the equation: qO2 = 40.1/(1 - e(-0.194t)), where qO2 is
      respiration rate and t is age. Allometric coefficients of the oxygen consumption
      rate-soft tissue weight relationship were also determined.

PMID- 15559135
TI  - [Thermoregulatory activity of dermorphin fragments].
AB  - We studied the effect of C-terminal truncation of the dermorphin (DM) molecule
      and analogs of its N-terminal tetrapeptide, [DOrn2]-DM(1-4), [DArg2]-DM(1-4),
      [DAla4]-DM(1-4), [DArg2, DAla4]-DM(1-4), Arg-DM(1-4), Arg-[DArg2]-DM(1-4), Arg
      [DAla4]-DM(1-4), and Arg-[DArg2, DAla4]-DM(1-4), on the functional status of the
      thermoregulation system in rats at different ambient temperatures. For the first
      time, we demonstrate that the N-terminal tetrapeptide is the minimal fragment
      with the hypothermic effect. Only the N-terminal octapeptide exerted the
      vasomotor effect. Amino acid substitutions in the tetrapeptide affected its
      hypothermic effect. [DArg2]-DM(1-4) and [DArg2, DAla4]-DM(1-4) had the greatest
      effect. Addition of Arg to the N-terminus of DM(1-4) analogs changed their
      thermoregulatory activity. The greatest thermoregulatory effect was observed for
      Arg-[DArg2]-DM(1-4) and Arg-[DArg2, DAla4]-DM(1-4).

PMID- 15559136
TI  - [Effect of gamma irradiation on the preference behavior and lipid metabolism in
      grey garden slug Deroceras reticulatum Mull].
AB  - We studied the preference behavior of slugs Deroceras reticulatum in experimental
      light, thermal, and salt gradients. The zone of each gradients preferred by the
      majority of individuals had the lowest contents of total lipids and total fatty
      acids in the tissues as compared to animals in any other zones. Hard gamma
      irradiation of slugs D. reticulatum proved to induce qualitative changes in salt
      preference, to decrease photoresponse in light gradients, and to increase lipid
      content in tissues.

PMID- 15559137
TI  - [Effect of the heparin-lysine complex on the hemostatic and insular systems].
AB  - We studied the effect of chronic intraperitoneal administration of heparin-lysine
      complex on the state of the hemostatic and insular systems in young and senescent
      animals (rats). This complex exerted a positive effect on physiological function
      of the coagulant, anticoagulant, and fibrinolytic components of the hemostatic
      system in the norm and in developing experimental alloxan diabetes. In this case,
      both the complex and its components, lysine and heparin, had a pronounced
      antidiabetogenic effect.

PMID- 15559138
TI  - [Antiulcer effects of the tripeptide PGP and its possible metabolites (PG, GP,
      glycine, and proline) in different models of ulcer induction in rats].
AB  - The study of the effect of equimolar concentrations (3.7 micromol/kg) of the
      tripeptide PGP and its possible metabolites--PG, GP, proline, and glycine--on
      ethanol-, stress-, and indomethacin-induced ulcer development in rats showed that
      only PGP exhibited consistent antiulcer effects on all three ulceration models.
      Glycine and proline tended to increase the area of indomethacin-induced lesions
      in the stomach. PG reduced the ethanol- and indomethacin-induced lesions
      approximately twofold but was considerably less effective in stress-induced
      ulcer. GP decreased the stress- and indometacin-induced ulcer but tended to
      stimulate the ethanol-induced lesions. The results of this study indicate that
      the antiulcer activity of PGP may be related to the effect of this tripeptide
      itself and to proteolysis of PGP to dipeptides and amino acids as well.

PMID- 15559139
TI  - [Temperature as a factor of niche separation in free-living mesostigmatid mites
      (Mesostigmata: Arachnida, Parasitiformes) of storm detritus].
AB  - We carried out a laboratory investigation of temperature effect on survival as
      well as reproductive and trophic activities of mesostigmatid mites.
      Representatives of gamasid (three species) and uropodid (two species) mites
      abundant in storm detritus were used as model species. The upper reproduction
      limit and the upper survival limit were determined for the mites and their preys
      in the thermal range of 29-47 degrees C. Most of studied species managed to
      survive and propagate in a wide thermal range corresponding to the thermal
      gradient in the peripheral zones of the algal belts. The role of temperature as a
      factor of ecological niche separation in saprophytic Mesostigmata and formation
      of polydominant mite communities in the algal belts were demonstrated.

PMID- 15559140
TI  - [Nanobiology of the ocean].
AB  - The concepts of nanobiotic forms and their relationships with oceanic organic
      matter and feeding as well as their role in oceanic communities are proposed on
      the basis of long-term electron microscopy and microbiological studies initiated
      in 1969 in the Barents Sea, Atlantic and Pacific oceans, and marginal seas of the
      Arctic Ocean.

PMID- 15559141
TI  - [Ecological factors of hydrolytic enzyme activities in the Ob-Yenisey estuarine
      coastal waters in winter and their modelling].
AB  - The ice conditions at the Ob-Yenisey estuarine coastal waters with relatively
      diffuse ice cover have been described using the data obtained in the Kara Sea
      survey aboard the nuclear icebreaker Yamal in January 22-March 6, 2003. The data
      on the capacity and rate of enzymatic degradation of various forms of organic
      matter and on the associated ecological factors in the region of active sea
      water/continental water interaction are given. We analyzed spatial distribution
      of the main types of water bodies as well as the cascade structure formed by some
      biogeochemical barriers near the Ob-Yenisey flaw polynya. We also analyzed the
      correlations between the indices of extracellular biochemical activity in water
      and the main abiotic and biotic factors during the organotrophic phase. The
      processes determining the level of biochemical activity in winter water and the
      rates of potential degradation of various organic compounds are considered.

PMID- 15559142
TI  - [Tissue hemoglobins of Gastropoda (Mollusca)].
AB  - The distribution and content of tissue hemoglobins in the radular muscle,
      subradular cartilages, myocardium, and nerve tissue of gastropods are analyzed.

PMID- 15559143
TI  - [From genetics of intraspecific differences to genetics of intraspecific
      similarity].
AB  - Based on the Mendelian approach to heredity, modern genetics describes
      inheritance of characters belonging to the category of intraspecific difference.
      The other large category of characters, intraspecific similarity, stays out of
      investigation. In this review, the genome part responsible for intraspecific
      similarity is considered as invariant and regulatory. An approach to studying the
      invariant part of the Drosophila melanogaster genome is formulated and the
      results of examining this genome part are presented. The expression of mutations
      at genes in the invariant genome part is different from that of Mendelian genes.
      We conclude that these genes are present in the genome in multiple copies and
      they are functionally haploid in the diploid genome. Severe abnormalities of
      development appearing in the progeny of mutant parents suggest that the mutant
      genes are genes regulating ontogeny. A hypothesis on an elementary ontogenetic
      event is advanced and the general scheme of ontogeny is presented. A concept on
      two types of gene allelism (cis- and trans-allelism) is formulated. This approach
      opens a possibility for studying genetic material responsible for the formation
      of intraspecific similarity characters at different taxonomic levels on the basis
      of crossing individuals of the same species.

PMID- 15559144
TI  - [Analysis of the formation and autonomous replication of an extrachromosomal
      mouse transgene].
AB  - A stable autonomously replicating shuttle transgene, pr8a was, previously
      isolated from Bombix mori and characterized. Autonomous replication of pr8a and
      its derivatives was observed in yeast cells, B. mori embryos, and transgenic
      mice. To continue the previous studies, transgenic mice of several generations
      were examined. DNA analysis revealed a course of pr8a rearrangements resulting in
      extrachromosomal transgene p8-2 of F2 transgenic mice. Consecutive directional
      elimination of vector DNA fragments was characteristic of rearrangements
      affecting autonomous transgenes in mouse cells. Analysis of the data obtained
      with transgenic mice and other organisms made it possible to identify the pr8a
      fragment that acts as minimal ARS in transformed yeast cells and transgenic mice.
      Another pr8a region was assumed to be a component of a pr8a ARS module involved
      in regulating autonomous replication. Inserted in two different integrative
      vectors, minimal ARS ensured their autonomous state in transformed yeast cells
      and transgenic mice. Transgenes pr8a and p8-2, along with some other well-known
      constructs, were considered as prototype autonomously replicating vectors
      suitable for studying the mechanism of autonomous replication and solving some
      problems of gene therapy.

PMID- 15559145
TI  - [Genetic regulation of pathogenicity and virulence factors in bacteria Erwinia
      carotovora subsp. atroseptica: identification of kduD gene].
AB  - A mutant that cannot utilize pectin substances of plant cell walls was obtained
      via insertion of mini-mini-Tn5xylE transposon into the chromosome of
      phytopathogenic bacteria Erwinia carotovora subsp. atroseptica. The inability of
      mutant cells to utilize these substrates was caused by a failure to accomplish
      the catabolism of unsaturated digalacturonic acid (UDA). Study of enzymatic
      activities has established that mutant bacteria lost the ability to produce 2,5
      diketo-3-deoxygluconate dehydrogenase, an enzyme of intracellular UDA
      utilization. Molecular cloning of the mutant gene was conducted, and its
      nucleotide sequence was determined. It was shown that the nucleotide sequence of
      this gene had an 82% homology with the sequence of Erwinia chrysanthemi EC3937
      kduD gene encoding 2,5-diketo-3-deoxygluconate dehydrogenase. The intergene kdul
      kduD region in bacteria Erwinia carotovora subsp. atroseptica is shorter in
      length by 98 nucleotides than the corresponding region of Erwinia chrysanthemi
      and does not contain promoter sequences. The kduD gene was located at 126.8 min
      of the Erwinia carotovora subsp. atroseptica genetic map.

PMID- 15559146
TI  - [Genetic regulation of pathogenicity and virulence factors in bacteria Erwinia
      carotovora subsp. atroseptica: phenotypic characteristic of bacteria with the
      mutant kduD gene].
AB  - In contrast to the closely related bacteria Erwinia chrysanthemi, bacteria
      Erwinia carotovora subsp. atroseptica produce lower levels of main pathogenicity
      and virulence factors (pectate lyases, cellulases, and proteases) in the presence
      of pectins. This effect was shown to be connected with the accumulation of the
      intermediate product of intracellular degradation of these substances, 2,5-diketo
      3-deoxygluconate (DK2). The presence of DK2 in the culture broth of mutant
      bacteria, connected to its export in the environment, was established. The
      production of pectate lyases, cellulases, and proteases is repressed by DK2 only
      at its high concentrations in the cultivation medium, whereas low concentrations
      of DK2 induce the production of virulence factors. Genes involved in the
      intracellular catabolism of pectin substances and induced by both low and high
      DK2 concentrations in the cultivation medium are not repressed by this
      metabolite.

PMID- 15559147
TI  - [Gene pool of pig breeds in southern region of Ukraine as determined from
      immunogenetic parameters].
AB  - On the basis of the long-term observations of 22 334 pedigree animals, the level
      of genetic polymorphism and basic breed-specific immunogenetic parameters were
      determined in eight major pig breeds from southern Ukraine. The high level of
      gene diversity was revealed and the degree of genetic similarity between the
      studied breeds was estimated.

PMID- 15559148
TI  - [The effect of heterosis on inheritance of quantitative traits in silkworm
      exposed to electromagnetic irradiation].
AB  - The effect of heterosis was studied in several quantitative traits of clone breed
      and interbreed silkworm hybrids exposed to electromagnetic irradiation (lambda =
      1.6 cm, power density 700 microW/cm2) during postdiapause embryonic development.
      The influence of the type of reproduction on the manifestation of irradiation
      effects in the next generation was also examined. In hybrids, the resistance to
      low-intensity high-frequency irradiation was higher than in the parental forms.
      Unlike the latter, the hybrids showed no significant modification of the traits
      after the exposure to electromagnetic irradiation. In the second generation, the
      modifying effect of irradiation is retained in the case of parthenogenetic
      silkworm development but not after mating.

PMID- 15559149
TI  - [Polymorphism and inheritance of seed storage protein in sunflower].
AB  - The data on polymorphism and inheritance of the seed storage protein helianthinin
      are presented. The results of hybrid analysis indicate that in the annual
      sunflower Helianthus annuus, helianthinin synthesis is controlled by at least
      three loci: HelA, HelB, HelB, and HelC. Codominant alleles controlling different
      electrophoretic variants of polypeptides were identified at each of the loci. The
      HelA locus was inherited independently of HelB and HelC in a series of dihybrid
      crosses. The frequencies of recombination between loci HelB and HelC estimated in
      F2 and BC of two crossing combinations were respectively 21.8 and 19.0%.
      Segregation of the Hel-C-controlled variants in the progenies from the crosses of
      cultured sunflower with annual wild species and forms corresponded to that
      theoretically expected for Mendelian inheritance. The maternal type of
      helianthinin inheritance was observed in the progenies from the crosses of inbred
      H. annuus lines with perennial diploid and polyploid Helianthus species. Altered
      expression of the HelC locus was detected in some hybrid combinations. These
      alterations appeared in early (F1, F2) hybrid generations and were similar in
      different hybrid combinations. They did not depend on the perennial paternal
      species being more influenced by the maternal genotype and by the mode of
      obtaining hybrids (in an embryo culture or in the field). These results are
      explained by "genomic shock" generated by hybridization of genetically
      incompatible species.

PMID- 15559150
TI  - [The effect of Lr19-translocation on in vitro androgenesis and inheritance of
      leaf-rust resistance in DH3 lines and F2 hybrids of common wheat].
AB  - Leaf-rust resistance and androgenesis were studied in the anther cultures of
      Triticum aestivum L., which included Saratovskaya 29 cultivar, the isogenic line
      Ps29, and three F1 hybrids (L503/S55, L504/S58, ATS7/L1063) with 7DS-7DL-7Ae#1L
      translocation of Lr19 gene (Lr19 translocation) from Agropyron elongatum (Host)
      P.B. The Lr19 translocation was shown to affect the induction of embryogenesis
      and green plant regeneration. The frequencies of Lr19 translocation differed in
      F2 hybrids obtained by traditional hybridization and in sets of DH lines obtained
      in F1 anther cultures derived from the same combinations of T. aestivum parental
      forms. The number of leaf-rust resistant genotypes tended to decrease. The
      frequency of Lr19 translocation in the set of DH3 lines derived from F1 L504/S58
      was significantly lower than in other sets of DH3 lines and F2 hybrid
      populations.

PMID- 15559151
TI  - [Barley chromosome identification using genomic in situ hybridization in the
      genome of backcrossed progeny of barley-wheat amphiploids [H. geniculatum All.
      (2n = 28) x T. aestivum L. (2n = 42)] (2n = 70)].
AB  - Genomic in situ hybridization (GISH) has been used to study characteristics of
      the formation of alloplasmic lines detected among self-pollinated backcrossed
      progeny (BC1F5-BC1F8) of barley--wheat amphiploids [Hordeum geniculatum All. (2n
      = 28) x Triticum aestivum L. (2n = 42)] (2n = 70). The chromosome material of the
      wild barley H. geniculatum has been shown to contribute to these lines. For
      example, fifth-generation plants (BC1F5) had genotypes (2n = 42w + 2g), (2n = 42w
      + 1g + 1tg), and (2n = 41w + 1g), where w is common wheat chromosomes, g is
      barley (H. geniculatum) chromosomes, and tg is the telocentric chromosome of wild
      barley. Beginning from the BC1F6 generation, alloplasmic telocentric addition
      lines (2n = 42 + 2tg) and (2n = 42 + 1tg) appear. This lines has been found
      cytogenetically unstable. The progeny of each of these cytological types include
      not only the (2n = 42 + 2tg) and (2n = 42 + 2tg) addition plants, but also plants
      with the monosomic (2n = 41 + 1tg) and the disomic (2n = 40 + 2tg) substitutions,
      as well as the (2n = 41 + 2tg) plants, which lack one wheat chromosome and have
      two telocentric barley chromosomes. It has been demonstrated that the selection
      for well-filled grains favors the segregation of telocentric addition lines (2n =
      42 = 2tg) and (2n = = 42 + 1tg).

PMID- 15559152
TI  - [Origin of the house mice (superspecies complex Mus musculus sensu lato) from the
      Transcaucasian region: A new look at dispersal routes and evolution].
AB  - We analyzed our results and literature evidence on variability of nuclear protein
      genes in 39 populations of eight synanthropic and wild species of house mice
      (superspecies complexes Mus musculus and M. spicilegus) from Transcaucasia,
      Eastern and Western Europe, Near and Middle East, Central, South, and East Asia,
      and Cuba. These data were for the first time ever combined into a single database
      by unification of nomenclature of 21 loci examined by different authors in 39
      populations. Analysis of geographical allele distribution have shown that
      populations of domestic Transcaucasian mice are close to Indo-Pakistani
      populations of form oriental of the species M. castaneus, which preserved a high
      level of ancestral polymorphism. We concluded that a very heterogeneous, rich
      gene pool of house mice from Transcaucasia could not develop only by secondary
      contacts of differentiated M. musculus s. str. and M. domesticus forms, since it
      is similar to the ancestral gene pool of the superspecies complexes M. musculus
      and M. spicilegus. In this context, unique characteristics of some Central Asian
      populations were examined; these populations may have served as a "transit
      station" in the dispersal of synanthropic house mice forms. We suggest that the
      Transcaucasian populations are genealogically closely related to an early Near
      East form of M. musculus, which, as M. domesticus and M. castaneus, split from
      the common ancestor and preserved nondifferentiated pool of ancestral alleles of
      protein genes. This hypothesis admits the involvement of differentiated species
      M. musculus s. str. and M. domesticus in the ultimate formation of the gene pool
      of Transcaucasian house mice. Apparently, these populations resulted from
      alternation and (or) "overlapping" of different evolutionary processes. A
      scenario suggesting that hybrid events having occurred in Transcaucasia at
      different times, were "superposed" on the gene pool of the ancient autochtonous
      population of house mice from this region seems most plausible. Analysis of
      allozyme variability in the modern Transcaucasian Mus populations could not
      always distinguish between ancestral polymorphism and hybridization consequences.

PMID- 15559153
TI  - [Insertion-deletion polymorphism of mitochondrial DNA region V in Kazakh
      populations from different regions of Kazakhstan].
AB  - Insertion-deletion polymorphism of the mitochondrial DNA (mtDNA) region V was
      examined in three Kazakh populations inhabiting different regions of Kazakhstan.
      The 9-bp deletion was revealed in all three populations examined. In Altai
      population the 4-bp insertion was also found. The presence of these polymorphic
      variants was confirmed by DNA sequencing.

PMID- 15559154
TI  - [Genetic and epidemiologic analysis of hereditary diseases of the nervous system
      in the cities of Volgograd and Volzhskii].
AB  - A genetic epidemiological study of hereditary diseases of the nervous system
      (HDNS) was conducted in the cities of Volgograd and Volzhsky for the first time.
      In total, 1 323 500 individuals were examined including the populations of
      Volgograd and Volzhsky (1 012 800 and 310 700 persons, respectively). The
      prevalence of neurological diseases with autosomal dominant (AD), autosomal
      recessive (AR), and X-linked recessive inheritance was estimated. These data were
      compared with the estimates previously obtained for different population of the
      Russian Federation. A decrease was found in general HDNS load in Volgograd and
      Volzhsky. The compared populations were shown to differ in a contribution of AD,
      AR, and X-linked recessive diseases into the HDNS load formation. The possible
      effect of population dynamics factors on the HDNS load structure is discussed.

PMID- 15559155
TI  - [Nozological spectrum of hereditary diseases of the nervous system in the cities
      of Volgograd and Volzhsky].
AB  - A spectrum of hereditary diseases of the nervous system (HDNS) was studied in the
      cities of Volgograd and Volzhsky. The estimates were obtained for the prevalence
      of major HDNS groups and individual nosological forms. The populations examined
      differed in prevalence of this pathology and in contribution of individual
      diseases and their nosological forms into HDNS load formation. The effect of the
      population dynamics in Volgograd and Volzhsky on the HDNS prevalence is
      discussed.

PMID- 15559156
TI  - [The rate of approach to the equilibrium value of F(ST) in island and one
      dimensional stepping-stone models of migration].
AB  - The rate of approach to the equilibrium value of FST was analyzed numerically for
      the finite island and one-dimensional stepping-stone models using computer
      simulation. For both models, this rate was shown to decrease with decreasing
      migration rate among subpopulations but in the case of the stepping-stone model,
      it takes thousands rather than tens of generations to reach the equilibrium.
      Unlike the island structure of migration, in the stepping-stone model an increase
      in the subpopulation number reduces the rate of reaching the equilibrium state.

PMID- 15559157
TI  - [Resistance to fungal diseases in hybrid progeny from crosses between common
      wheat variety Saratovskaia 29 and the amphidiploid Triticum timopheevii/Triticum
      tauschii (AAGGDD)].
AB  - The progeny of BC6F2-BC9F(2)-4 has been analyzed for resistance to brown rust (Lr
      genes) and powdery mildew (Pm genes). This progeny was obtained due to
      introgression of the alien material from the synthetic hexaploid wheat Triticum
      timopheevii/Aegilops squarrosa (= Triticum tauschii AAGGDD, 2n = 42) into the
      common wheat variety Saratovskaya 29. Against the background of natural
      infection, the lines resistant to both diseases and to either of them were
      developed. The brown-rust and powdery-mildew resistance is controlled by one/two
      effective independent genes Lr and Pm.

PMID- 15559158
TI  - [Chemically induced Drosophila melanogaster mutants with changes in brain
      structure].
AB  - Neurodegenerative human diseases are caused by nerve cell death and anatomical
      changes in some brain regions. Molecular genetic studies of Drosophila showed
      that this organism can serve as a valuable test-system for conserved mechanisms
      underlying human nervous system disorders. Analysis of brain functions is
      possible when the mutants with disturbed functions are available. In this study,
      we have developed a unique collection of Drosophila melanogaster mutants with
      morphological and neurodegenerative changes in brain structure, which were
      induced by chemical mutagens.

PMID- 15559159
TI  - [Genetic analysis of X-chromosome neurodegenerative mutants of Drosophila
      melanogaster induced by ethyl methansulfonate and nitrosoethylurea].
AB  - In a series of Drosophila mutants with changes in the brain structure, some
      characters (reduced life span, behavioral changes, and neuronal loss in various
      brain regions) resemble symptoms observed in human patients with
      neurodegenerative diseases. In addition, similar specific phenotypes shared by
      different species suggest that common mechanisms underlie degeneration of their
      nerve cell. This study reports the results of a genetic analysis of new X
      chromosome mutants with neurodegenerative changes in brain structure, which were
      induced by chemical mutagenesis. According to complementation test, all mutants
      were divided into three complementation groups, in which the life span and
      dynamics of neurodegenerative changes were studied. The life span of Drosophila
      melanogaster flies was found to depend on the state of their nervous system.

PMID- 15559160
TI  - Apolipoprotein E and A-IV polymorphisms in ethnic Russians living in Estonia.
AB  - 137 Russians living in Estonia was screened by isoelectric focusing and
      immunoblotting procedures to determine the distribution of genetic variations in
      apolipoprotein E (apoE) and apolipoprotein A-IV (apoA-IV) genes. The apoA-IV-2
      allele and epsilon4 allele frequency of the Russians tended to be lower than in
      most other European populations.

PMID- 15559161
TI  - Psychological stress and treatment--research issues.

PMID- 15559162
TI  - Mechanisms of cervical spine injuries for non-fatal motorcycle road crash.
AB  - Cervical spine injuries such as subluxation and fracture dislocation have long
      been known to result in severe consequences, as well as the trauma management
      itself. The injury to the region has been identified as one of the major causes
      of death in Malaysian motorcyclists involved in road crashes, besides head and
      chest injuries (Pang, 1999). Despite this, cervical spine injury in motorcyclists
      is not a well-studied injury, unlike the whiplash injury in motorcar accidents.
      The present study is a retrospective study on the mechanisms of injury in
      cervical spine sustained by Malaysian motorcyclists, who were involved in road
      crash using an established mechanistic classification system. This will serve as
      an initial step to look at the cervical injuries pattern. The information
      obtained gives engineer ideas to facilitate design and safety features to reduce
      injuries. All cervical spine injured motorcyclists admitted to Hospital Kuala
      Lumpur between January 1, 2000 and December 31, 2001 were included in the present
      study. Based on the medical notes and radiological investigations (X-rays, CT and
      MRI scans), the mechanisms of injuries were formulated using the injury mechanics
      classification. The result shows that flexion of the cervical vertebrae is the
      most common vertebral kinematics in causing injury to motorcyclists. This
      indicates that the cervical vertebrae sustained a high-energy loading at flexion
      movement in road crash, and exceeded its tolerance level. The high frequency of
      injury at the C5 vertebra, C6 vertebra and C5-C6 intervertebral space are
      recorded. Classification based on the Abbreviated Injury Scale (AIS) is made to
      give a view on injury severity, 9.1% of the study samples have been classified as
      AIS code 1, 51.5% with AIS 2 and 21.2% with AIS 3.

PMID- 15559163
TI  - Rotavirus RNA electropherotype in different states in Malaysia for the year 2000
      and 2001.
AB  - A total of 157 stool samples were examined for Group A rotaviruses in diarrheic
      children admitted to 8 different major hospitals in Malaysia. The overall
      incidence rate in this study was 19.7% (31 of 157) with a variation of 9.5% to
      39.1% in different locations. Majority of the infections detected were in those
      under 2 years of age and there were fewer admissions in the older age group. The
      stool samples were initially screened for rotavirus Group A by latex
      agglutination method and followed by RNA electrophoresis. The size and the
      characteristics wheel-shaped morphology of the viral preparations when examined
      by electron-microscopy further confirmed the presence of rotaviruses in the
      positive stool samples. Analysis of the RNA pattern showed that majority of the
      isolates, 51.6% (16 of 31) were Type IIC ('long' with comigration of RNA segments
      7 and 8), 35.5% (11 of 31) with Type IIG ('long' with comigration of segments 7,
      8, 9), 9.7% (3 of 31) with Type IG ('short' with comigration of RNA segments 7,
      8, 9) and 3.2% (1 of 31) of mixed or atypical pattern. It appeared that over a 12
      year interval, only one new or unusual rotavirus electropherotype was found. This
      is the first comprehensive report on the electropherotypes of rotaviruses
      covering eight different geographical locations in Malaysia and the data obtained
      is useful for understanding the geographic distribution and types of rotaviruses
      transmitting in Malaysia.

PMID- 15559164
TI  - Non-accidental fatal head injury in small children--a clinico-pathological
      correlation.
AB  - Non-accidental head injury leading to massive intracranial trauma has been
      identified as a leading cause of death in small children. In a typical case, a
      child usually below the age of one year is violently shaken, leading to rupture
      of the connecting veins between the dura mater and the brain substance with
      variable degrees of bleeding into the subdural space resulting in increased
      intracranial pressure. The accompanying venous thrombosis affecting the vessels
      of the brain substance leads to cerebral hypoxia and cellular death. In this
      study conducted throughout the year 1999, all children below the age of 3 years
      who were admitted to Hospital Kuala Lumpur and had died due to non-accidental
      injuries were included. Postmortems, including histopathological studies, were
      conducted to determine the most likely mechanisms of the injuries. Ten cases were
      identified for the whole year. In 2 cases, both below one year of age, the
      features presented showed evidence of violent shaking of the infants. In 6 other
      cases whose average age was 13 (range 4-24) months, there were evidences of
      direct trauma and violent shaking. In the last two cases, aged 24 and 33 months
      respectively, there was only evidence of direct trauma on the heads without being
      shaken. This study shows that death due to intracranial trauma caused by shaking
      with or without direct impact is the most frequent cause of mortality in abused
      children. Death due to direct impact between the head and another object is a
      less frequent occurrence.

PMID- 15559165
TI  - Alteration of lipid peroxidation and antioxidant enzymes in young Malaysian IDDM
      patients.
AB  - The present study was designed to explore the relationship between lipid
      peroxidation and antioxidant enzymes in young Malaysian insulin dependant
      diabetes mellitus (IDDM) patients. Indicative parameters of lipid peroxidation,
      activities of antioxidant enzymes and diabetes parameters were evaluated in
      single blood samples from 30 young type 1 diabetic patients and 30 healthy
      control subjects. Antioxidant enzymes namely superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx) were significantly decreased while plasma
      malondialdehyde (MDA), an indicator for lipid peroxidation was significantly
      increased in IDDM patients compared to control subjects. Positive correlations
      between HbA1c and MDA; fasting blood glucose (FBG) and MDA and negative
      correlations between HbA1c and SOD; MDA and SOD were observed in these patients.
      No significant correlation existed between HbA1c and fasting blood glucose, GPx
      or CAT in the diabetic patients. The strong correlations found between lipid
      peroxidation, antioxidant enzymes and diabetes parameters confirms the existence
      of oxidative stress in our IDDM patients.

PMID- 15559166
TI  - Outcome of stapes surgery for otosclerosis.
AB  - Otosclerosis is an autosomal dominant disease affecting the otic capsule. It is
      believed to be rare in Asian countries including Malaysia. We analyzed the
      results of 29 patients (35 ears) who had undergone stapes surgery for suspected
      otosclerosis from January 1996 to June 2002. The demographic data was analyzed.
      The procedure most commonly performed was stapedotomy. The closure of air bone
      gap after surgery was good at 2 kHz and 4 kHz compared to frequency below 2 kHz.
      Closure of air bone gap to within 10 dB was achieved in 74.3%. About 7.5% of our
      patients did not gain in average air conduction. The outcome of the procedure is
      comparable to those reported by authors who used the same evaluation criteria. No
      serious complications occurred in our patients.

PMID- 15559167
TI  - Non-achievement of clinical targets in patients with type 2 diabetes mellitus.
AB  - The study was conducted to determine whether the clinical targets for the control
      of diabetes recommended by American Diabetes Association can be met in the
      context of routine diabetes practice. This cross-sectional study was undertaken
      on 211 type 2 diabetic patients at the Outpatients Diabetes Clinic, Hospital
      Universisti Sains Malaysia (HUSM) Kubang Kerian, Kelantan between the year 2001
      2002. Patients' physical examination and their medical history as well as their
      family history were obtained by administering a structured questionnaire. Samples
      of patients' venous blood during fasting were taken and analysed for plasma
      glucose, glycated haemoglobin and lipid profile. Analysis showed that many
      patients had comorbidities or complications. A large number of them had poor
      glycaemic control (73%). Systolic and diastolic blood pressures of 75% and 85%
      subjects were > or = 130 and > or = 80 mmHg, respectively. Body Mass Index (BMI)
      values of 66% of the patients were outside the clinical target (BMI > or = 25 in
      male and > or = 24 kg/m2 in female). The lipid profile showed that 96% of the
      patients had at least one lipid value outside the clinical target level. In this
      study, 70% of the patients had total cholesterol > or = 5.2 mmol/L, 87% had LDL
      cholesterol > or = 2.6 mmol/L, 57% had HDL cholesterol less than the normal
      range, < or = 1.15 mmol/L in men and < or = 1.4 mmol/L in women, while 46% had
      triglycerides > or = 1.71 mmol/L. Complications of diabetes were observed in 48%
      of the total number of patients. As for the patients' systolic blood pressure,
      age and duration of diabetes were found to have significant effects. Older
      subjects with a longer duration of diabetes were more hypertensive. Variables
      that had significant effects on BMI were age, duration of diabetes, glycaemic
      control and gender. Younger females and newly diagnosed subjects with better
      glycaemic control (A1C < 7%) were found to have higher BMI values. The overall
      clinical targets were suboptimal. The prevalence of hyperlipidaemia and
      hypertension was high. It is imperative that better treatment strategies and
      methods be adopted to enhance diabetes control and reduce long-term complications
      of the disease.

PMID- 15559168
TI  - The comparison of QT dispersion and 24 hour ambulatory blood pressure monitoring
      amongst diabetic patients with and without microalbuminuria.
AB  - Diabetes mellitus is an important coronary artery disease risk factor. The
      presence of microalbuminuria, which indicates renal involvement in diabetic
      patients, is associated with an increased cardiovascular risk. There are
      suggestions that diabetic patients with microalbuminuria have more adverse risk
      profile such as higher ambulatory blood pressure and total cholesterol levels to
      account for the increased cardiovascular morbidity and mortality. QT dispersion
      is increasingly being recognized as a prognostic factor for coronary artery
      disease and sudden death. Some studies have suggested that QT dispersion is an
      important predictor of mortality in Type II diabetic patients. Our cross
      sectional study was to compare the QT dispersion and 24 hour ambulatory blood
      pressure monitoring between diabetic patients with microalbuminuria and those
      without microalbuminuria. Diabetic patients with overt coronary artery disease
      were excluded from the study. A total of 108 patients were recruited of which 57
      patients had microalbuminuria and 51 were without microalbuminuria. The mean
      value of QT dispersion was significantly higher in patients with microalbuminuria
      than in patients without microalbuminuria (58.9 +/- 27.9 ms vs. 47.1 +/- 25.0 ms,
      p < 0.05). The mean 24 hour systolic and diastolic blood pressures were
      significantly higher in patients with microalbuminuria than in patients without
      microalbuminuria (129.5 +/- 12.3 mm Hg vs 122.3 +/- 10.2 mm Hg, p < 0.05 and 78.4
      +/- 6.9 mm Hg vs 75.3 +/- 6.8 mm Hg, p < 0.05, respectively). Our study suggests
      that QT dispersion prolongation, related perhaps to some autonomic dysfunction,
      is an early manifestation of cardiovascular aberration in diabetic patients with
      microalbuminuria. The higher blood pressure levels recorded during a 24-hour
      period min diabetics with microalbuminuria could also possibly account for the
      worse cardiovascular outcome in this group of patients.

PMID- 15559169
TI  - The pattern of completed suicides seen in Kuala Lumpur General Hospital 1999.
AB  - A study was done on 76 suicide cases managed by the Forensic Pathology Department
      of Hospital Kuala Lumpur (HKL) from January till December 1999 to explore the
      pattern of suicide and psychiatric history. The Chinese contributed 52% (n=40) of
      cases followed by the Indians (29%, n=22) and the Malays (12%, n=9). After the
      age of sixty, 84.6% of the subjects were Chinese. The common methods of suicide
      were poisoning (39%), hanging (34%) and jumping from height (22%). Four out of 12
      case-notes traced had documented psychiatric history i.e. schizophrenia.
      CONCLUSION: the suicide rate for Kuala Lumpur is estimated at 7.4 per 100,000.
      The Indians has the highest suicide rate of 21.1 per 100,000 in keeping with
      other local studies. The suicide rate for the Chinese is 8.6 per 100,000, but it
      increased to 23 per 100,000 among the elderly Chinese. The suicide rate for
      Malays is 2.6 per 100,000, higher than what was cited in previous local studies.
      The incidence of jumping from height as a suicide method had doubled over the
      last 2 decades.

PMID- 15559170
TI  - Reliability and validity of the Pressure Management Inventory in a Malaysian
      population.
AB  - There is a general lack of valid tools to measure work stress of Malaysian. This
      study examines the validity and reliability of the Pressure Management Inventory
      (PMI). Reliability was evaluated using test retest method, and its correlation
      coefficient was calculated using Pearson's r. Internal consistencies were
      examined using Cronbach's Alpha. For precision, the Intraclass coefficients (ICC)
      were calculated for all the scales. Face Validity and Content Validity were
      assessed using an open-ended questionnaire on 6 content experts (psychiatrists in
      HKL). The results show good internal consistencies (alpha < or = 0.7) for most
      subscales, with the best results in the 'Pressure Scale'. The weak scales are
      'Individual-Differences' scale and 'Social Support' scale. The test-retest
      correlation coefficients were significant at the level of p<0.001 for all, except
      one scale. The ICC coefficients were high (>0.7) for most scales, particularly
      for Pressure, Health and Coping Scales. The PMI is a suitable, reliable and valid
      tool to measure stress of Malaysians. More in-depth study with a wider sampling
      needs to be carried out to add confidence of its usage on Malaysians.

PMID- 15559171
TI  - Psychological stress among undergraduate medical students.
AB  - The aim of this study was to determine the prevalence of psychological stress
      among medical students and to identify its symptoms and association with
      depression. A cross-sectional study design was used. Three-hundred and ninety-six
      medical students at a university in Malaysia were included in the study. Tools
      similar to the General Health Questionnaire (GHQ-12) and Beck Depression
      Inventory (BDI) were used to screen for psychological stress and depression,
      respectively. 41.9% of the medical students were found to have psychological
      stress, which was significantly associated with depression (chi2=4.636, df=1,
      p<0.05). Psychological stress is common among medical students and is associated
      with depression.

PMID- 15559172
TI  - Prevalence and causes of visual impairment and blindness in a rural population in
      Sepang district, Selangor.
AB  - A community based cross-sectional study was carried out to determine the
      prevalence and causes of visual impairment and blindness in residents aged forty
      years and above in kampung Jenderam Hilir of Sepang district, Selangor state. A
      total of 311 out of 341 (91.3%) respondents participated in this study. The
      prevalence of visual impairment and blindness observed was 18.9% and 2.9%
      respectively. The prevalence of visual impairment and blindness increased
      significantly with age. Amongst the 159 respondents who agreed for eye checkup,
      refractive errors (56%), cataract (20.1%), glaucoma (4.4%) and diabetic
      retinopathy (1.3%) were found to be causing visual impairment and blindness.

PMID- 15559173
TI  - Biopsy-proven childhood glomerulonephritis in Johor.
AB  - BACKGROUND: There has been no published study of biopsy-proven childhood
      glomerulonephritis in Malaysia. OBJECTIVES: To determine the pattern of childhood
      glomerulonephritis in Johor, Malaysia from a histopathological perspective and
      the various indications used for renal biopsy in children. MATERIALS AND METHODS:
      Retrospective study was done of all renal biopsies from children under 16 years
      of age, received in Sultanah Aminah Hospital, Johor between 1994 and 2001. The
      histopathological findings were reviewed to determine the pattern of biopsy
      proven glomerulonephritis. The indications for biopsy, mode of therapy given
      after biopsy and the clinical outcome were studied. RESULTS: 122 adequate
      biopsies were received, 9 children had repeat biopsies. Of the 113 biopsies,
      minimal change disease formed the most common histopathological diagnosis (40.7%)
      while lupus nephritis formed the most common secondary glomerulonephritis
      (23.0%). The main indications for biopsy were nephrotic syndrome (50.8%), lupus
      nephritis (25.4%) and renal impairment (13.1%). The mode of therapy was changed
      in 59.8% of the children. Of 106 patients followed-up, 84 children were found to
      have normal renal function in remission or on treatment. 4 patients developed
      chronic renal impairment and 16 reached end stage renal disease. Five of the 16
      children with end stage disease had since died while 11 were on renal replacement
      therapy. Another 2 patients died of other complications. CONCLUSIONS: The pattern
      of childhood GN in our study tended to reflect the more severe renal parenchymal
      diseases in children and those requiring more aggressive treatment. This was
      because of our criteria of selection (indication) for renal biopsy. Renal biopsy
      where performed appropriately in selected children may not only be a useful
      investigative tool for histological diagnosis and prognosis but may help
      clinicians plan the optimal therapy for these children.

PMID- 15559174
TI  - Breast cancer and lifestyle risks among Chinese women in the Klang Valley in
      2001.
AB  - Breast cancer is one of the commonest cancers among women in Malaysia. The
      relation between lifestyle practices and the risk of breast cancer in Chinese
      women aged 21-55 years were assessed using data collected from June to October
      2001, via a face-to face interview in a case control study in the Breast Clinics
      of Kuala Lumpur Hospital and University Malaya Medical Centre. A total of 89
      cases with breast cancer were compared with 85 controls without the disease. Our
      study showed that breastfeeding had an odds ratio of 4.43 after adjustment for
      confounders. The results add to the evidence of a protective association between
      breast feeding practices and breast cancer particularly among Chinese women
      receiving treatment at two government hospitals in the Klang Valley.

PMID- 15559175
TI  - Blood pressure in rural and urban adult healthy females of Jat Sikh community in
      Punjab, North India: an epidemiologic profile.
AB  - Blood pressure readings were collected from 1042 adult females of rural and urban
      Jat Sikh community of Punjab, a north Indian State. Anthropometric measurements
      like height, weight and skinfold thickness were also collected. The difference
      between rural and urban females in systolic, diastolic and mean arterial blood
      pressure was found to be statistically significant. All anthropometric variables
      and age have a significant positive association with blood pressure. The effects
      of anthropometric variables on blood pressure were assessed simultaneously
      through stepwise multiple regression analysis. All 'F' ratios have been found
      highly significant (p < 0.001) among both rural and urban female population.

PMID- 15559176
TI  - Job dissatisfaction in lecturers in School of Medical Sciences Universiti Sains
      Malaysia and Faculty of Medicine Universiti Kebangsaan Malaysia.
AB  - Job dissatisfaction in doctors and teachers is known to have direct consequences
      on the quality of service and teaching for patients and students respectively. A
      cross-sectional study to assess dissatisfaction in lecturers of School of Medical
      Sciences, Universiti Sains Malaysia (USM) and Faculty of Medicine, Universiti
      Kebangsaan Malaysia (UKM) was undertaken between August 2001 and May 2002. The
      original English version of the Job Content Questionnaire (CQ) version 1.7
      (revised 1997) by Robert Karasek was self-administered to 73 (response rate
      58.4%) and 80 (response rate 41.7%) lecturers in the medical faculties of USM and
      UKM, respectively. The prevalence of job dissatisfaction in USM and UKM lecturers
      were 42.6% and 42.9%, respectively; the difference was not significant (p>0.05).
      Risk factors of job dissatisfaction in USM lecturers were decision authority
      (p<0.001) and psychological job demand (p<0.001). Significant risk factors of job
      dissatisfaction in UKM lecturers were skill discretion (p<0.01) and psychological
      job demand (p<0.001). We conclude that psychological job demand was a risk factor
      of job dissatisfaction in both USM and UKM lecturers; in USM, decision authority
      was protective, while in UKM, skill discretion was protective against job
      dissatisfaction.

PMID- 15559177
TI  - Cognitive impairment among the elderly in a rural community in Malaysia.
AB  - Cognitive impairment is common in late life and may be due to the normal process
      of ageing or associated with physical or mental disorders. The aim of this study
      was to determine the prevalence of cognitive impairment among the elderly in a
      rural community setting. A cross sectional study design using stratified
      proportionate cluster sampling method was used in this study. A questionnaire
      similar to the Elderly Cognitive Assessment Questionnaire (ECAQ) was used as a
      screening instrument for cognitive impairment. The prevalence of cognitive
      impairment was 22.4% (50/223) among the elderly respondents. Cognitive impairment
      among the elderly was significantly associated with age, gender, ethnicity,
      marital status and level of education.

PMID- 15559178
TI  - Reliability and validity of the Spielberger State-Trait Anxiety Inventory (STAI)
      among urological patients: a Malaysian study.
AB  - To validate the English version of the Spielberger State-Trait Anxiety Inventory
      (STAI) in a sample of Malaysia patients with and without urinary symptoms.
      Validity and reliability were studied in patients with lower urinary tract
      symptoms (LUTS) and patients without LUTS. Reliability was evaluated using the
      test-retest method and internal consistency was assessed using Cronbach's alpha.
      Sensitivity to change was expressed as the effect size in the pre-intervention
      versus post-intervention score in additional patients with LUTS who underwent
      transurethral resection of the prostate (TURP). Internal consistency was
      excellent. A high degree of internal consistency was observed for each of the 40
      items with Cronbach's alpha value = 0.38 to 0.89 while the Cronbach's alpha for
      the total scores was 0.86. Test-retest correlation coefficients for the 40 items
      score were highly significant. Intraclass correlation coefficient was high
      (ICC=0.39 to 0.89). A high degree of sensitivity and specificity to the effects
      of treatment was observed. A high degree of significant level between baseline
      and post-treatment scores was observed across nearly half of the items in
      surgical group but not in the non-LUTS group (control subjects). The STAI is
      reliable, valid and sensitive to clinical change in a sample of Malaysian
      patients with and without urinary symptoms.

PMID- 15559179
TI  - Prevalence and associated factors of job-related depression in laboratory
      technicians in Hospital Universiti Sains Malaysia (HUSM) and Ministry of Health
      Malaysia (MOH) Hospitals in Kelantan.
AB  - Karasek's job strain model postulates that workers chronically exposed to adverse
      psychosocial work environment (high strain job)--high psychological job demands
      and low job control, including poor social support, increased physical demand and
      hazardous work condition--will eventually develop both physical illnesses such as
      cardiovascular diseases and psychological disorders such as depression. In order
      to determine the prevalence and associated factors of job-related depression, a
      cross-sectional study was conducted among laboratory technicians in Hospital
      Universiti Sains Malaysia (HUSM) and Kementerian Kesihatan Malaysia (KKM)
      Hospitals in Kelantan between September 2001 and February 2002. One hundred and
      two laboratory technicians in HUSM and 79 laboratory technicians in 7 KKM
      Hospitals were selected; 84/102 (82.4%) in HUSM and 71/79 (89.9%) in KKM
      Hospitals responded. Data was collected using self-administered questionnaires of
      the validated Malay version of the Job Content Questionnaire (JCQ) originally
      developed by Robert Karasek. Results indicated that the prevalence of high job
      strain in laboratory technicians in HUSM and KKM hospitals was 33.3% (28/84) and
      26.8% (19/71), respectively (p>0.05). Significantly higher proportion (59.5%)
      (50/84) of laboratory technicians in HUSM compared to those in KKM Hospitals
      (39.4%) (28/71) (p = 0.016) experienced job-related depression. Significant
      associated factors of job-related depression were low social support (HUSM:
      adjusted OR 4.7, 95% CI 1.2-18.8; KKM: adjusted OR 14.8, 95%CI 2.4-89.3), high
      psychological demand (HUSM: adjusted OR 3.0, 95%CI 1.0-8.8), and low decision
      authority (KKM: adjusted OR 9.7, 95%CI 1.0-91.1). We conclude that strengthening
      the social support network (supervisors' and coworkers' support), reducing
      psychological job demand, and increasing decision-making authority of laboratory
      technicians may go a long way towards reducing job-related depression.

PMID- 15559180
TI  - Thoracic endometriosis: a report of two cases.
AB  - We describe two patients with recurrent hemopneumothorax associated with pelvic
      endometriosis. The first patient a 37-year-old nulliparous lady with recurrent
      bilateral hemopneumothorax. She had a past history endometriosis years earlier.
      Laparoscopy and biopsy confirmed widespread endometriosis including in the
      omentum. Recurrence of the hemopneumothorax stopped after danazol therapy
      suggesting thoracic endometriosis as the cause of hemopneumothorax. The second
      lady is 47-years old with 2 children. She first presented with hemopneumothorax
      associated with menstrual period but ultrasound of pelvis did not reveal evidence
      of endometriosis. However, when she presented with a second episode of
      hemopneumothorax one year later, she was confirmed to have endometriosis and no
      further recurrence after treatment with Gonadotropin-releasing hormone analogue.

PMID- 15559181
TI  - Bogota bag in the treatment of abdominal wound dehiscence.
AB  - A patient who underwent emergency laparotomy for rectal prolapse developed
      repeated abdominal wound dehiscence and subsequently an enteric fistula. The
      management of abdominal wound dehiscence is discussed, specifically with regards
      to the Bogota bag. Use of Bogota bag has been reported worldwide but this may be
      the first report here.

PMID- 15559182
TI  - Intestinal parasitic infections and micronutrient deficiency: a review.
AB  - Malnutrition including vitamin A and iron deficiency and parasitic diseases have
      a strikingly similar geographical distribution with the same people experiencing
      both insults together for much of their lives. Parasitic infections are thought
      to contribute to child malnutrition and micronutrient deficiency through subtle
      reduction in digestion and absorption, chronic inflammation and loss of
      nutrients. Parasites may affect the intake of food; it's subsequent digestion and
      absorption, metabolism and the maintenance of nutrient pools. The most important
      parasites related to nutritional status are intestinal parasites especially soil
      transmitted helminthes, Giardia duodenalis, Entamoeba histolytica, followed by
      other parasites such as the coccidia, Schistosoma sp. and malarial parasites.

PMID- 15559183
TI  - Methodology for small clinical trials.
AB  - Small clinical trials are trials in which the number of patients does not enable
      the objective of the study to be appropriately met with the usual methodological
      rules. This situation is common in the case of rare diseases, in paediatrics, in
      certain cancer pathologies or when the number of patients exposed to the
      treatment needs to be limited. The principal methodological problems are
      initially identified, and the classical methods (controlled, randomised, double
      blind trial using parallel groups, crossover trial, factorial design, trial
      performed with several measures repeated over time, add-on design, randomised
      withdrawal design or early-escape design) and more uncommon methods (sequential
      approaches, meta-analyses, the 'N of 1' method and other methods that facilitate
      decision making or modelling) are then discussed. Subsequently, recommendations
      are made to ensure that the results obtained are not a matter of chance, and to
      increase the level of proof.

PMID- 15559184
TI  - Clinical trial simulation in drug development.
AB  - The simulation of therapeutic models and clinical trial simulation have recently
      attracted attention as emerging techniques for developing new active molecules
      and the exploration of possible clinical trial results. Such approaches have
      benefited from fundamental progress in the development of 'in silico' models, as
      well as progress in nonlinear mixed-effect pharmacokinetic-pharmacodynamic
      models. Mixing the two approaches allows simulation of 'virtual' patients, who
      receive virtual treatments or placebo. These have various uses, such as proof of
      concept, decision analysis or experimental design optimisation. Also, the effect
      of departures from protocol on clinical trial results can easily be evaluated by
      the use of simulation. This technique is now implemented by the pharmaceutical
      industry for optimising phase II and III experimental designs when a good
      biomarker or a clinical outcome model is available, but the use of an in silico
      therapeutic model as a proof of concept is only just beginning. In order to see
      such methodologies used more widely in drug development, multidisciplinary
      efforts need to be initiated, new modelling and simulation tools developed, and
      sound modelling and simulation practice documents need to be adopted. A reduction
      in the number of failed clinical development projects, the number of negative
      phase II and III clinical trials, or in just their cost and duration, are among
      the expected benefits of modelling and simulation in clinical drug development.

PMID- 15559185
TI  - How can the safety of biotherapy products be ensured for patients?
AB  - The topic of the round table being very broad, it was agreed with the
      participants that the discussion should be focused on autologous cell therapy
      (CT) used in tissue repair, immunomodulation or gene transduction. Autologous CT
      is actually comprised of both very innovative procedures as well as of products
      used in routine clinical practice. In France, the regulatory framework for CT has
      now been finalised, underlining the fact that a CT product (CTP) is intrinsically
      linked to the process used in its preparation. The objective of this round table
      was to define the essential prerequisites for the development of therapies
      involving ex vivo cell preparations and, more specifically, to address the issues
      associated with patient safety during the course of product development. The
      different stages of CTP development were considered: (i) requirements for CTP
      manufacturing in order to guarantee product quality; (ii) nonclinical
      development, and selection of appropriate animal models to provide the proof of
      the concept and support the definition of CTP specifications; and (iii) clinical
      development and methodological specificities of CTP development. The specific
      problems associated with the use of ancillary therapeutic products (ATPs) during
      the development of a CTP were discussed. Actions were proposed to ensure long
      term supply of ATPs, which may be a significant bottleneck for the development of
      CT in France. Eventually, new regulatory provisions will come into force in the
      area of biovigilance, and it was deemed necessary for healthcare and industry
      professionals to be appropriately involved in the implementation phase.

PMID- 15559186
TI  - The results of major clinical trials: critical assessment, the circulation of
      information and media coverage.
AB  - The round table elected to focus its discussion on trials that, in terms of their
      importance, are likely to modify medical practices and behaviour. Such trials may
      be pre- or postmarketing studies. For the findings of a trial to result in a
      change in practice, they must be credible and fulfil the basic methodological
      criteria. It is nonetheless appropriate to complete that binary assessment by the
      use of an assessment checklist appropriate to each category of users, i.e. the
      Regulatory Agency, prescribing physicians and patients, who are sometimes
      informed directly by the media. The members of the round table proposed the
      'Giens 2003 checklist'. It consists of an interpretative semi-quantitative
      assessment checklist based on simple messages relevant to practice. Critical
      assessment is a necessary prelude to the circulation of the results to the
      various parties involved (healthcare professionals, patients, patient
      associations, the media and the general public) and the process of informing
      those parties in readily understandable but accurate terms. The practical
      implementation of the results, with a change in behaviour and/or the issuing of
      guidelines, are subsequent stages for which a certain lag time is inevitable. The
      assessment of implementation programmes, together with an accurate analysis of
      the obstacles to changing medical practice, should, in the future, improve and
      accelerate the implementation of important results in order to optimise patient
      management.

PMID- 15559187
TI  - Adaptation of the clinical trials directive: recommendations on the contents of a
      dossier for the request for authorisation of the first trials in human subjects.
AB  - The European Directive on clinical trials of medicinal products will fall within
      the scope of the legislation of Member States on 1 May 2004. In France, this
      adaptation will be carried out by a public health bill concerning, among other
      things, the reform of the current Huriet-Serusclat law, and by means of
      regulations. For trials concerning the initial administration of a product to
      human subjects, the group suggested the following recommendations: In French
      texts, to include a deadline of 30 days for the initial authorisation by the
      competent authority (Afssaps [Agence francaise de securite sanitaire des produits
      de sante]). To maintain an observed deadline of 20 days (35 official days) for
      the decision of the Ethics Committee (EC) [Committee for the Protection of
      Persons (CPP)]. To obtain a more specific evaluation of the pharmaceutical
      dossier of the investigational medicinal product (IMP) from the competent
      authority. To provide both bodies with nonclinical and possibly clinical data
      concerning the IMP information of the participants and their consent. To follow
      the recommendations posted on the Afssaps website for the entire IMP dossier. To
      submit a protocol under the International Committee on Harmonisation (ICH) E6
      format adapted for phase I and, possibly as a separate document, justification of
      a certain number of points (a total of ten) that are more specific to this trial
      phase to facilitate and improve the document review while also providing the
      expected guarantees. To limit the 'substantial' amendments to those provided for
      in the European guidelines. To break the blind for every serious event reported
      to the sponsor by the investigator, and report to the competent authority any
      serious adverse event related to the IMP or to the trial or without documented
      cause, while keeping ECs and investigators informed. Furthermore, certain points
      concerning the authorisations for packaging, labelling and dispensing of the
      batches of medicinal products for clinical trials will need to be specified for
      these early studies. All these recommendations are intended to help promote the
      development of studies involving the initial administration of medicinal products
      in France.

PMID- 15559188
TI  - [Transfusion of homologous red cells: products, indications and alternatives].

PMID- 15559189
TI  - [Purification and breaking techniques for cysts of Giardia spp].
AB  - The purpose of this study was to optimize and evaluate the purification
      techniques, isolation and breaking of cysts of Giardia spp from fecal samples to
      isolate DNA. Filtrated fecal samples were tested in 3 purification techniques:
      Telleman solution, sucrose and Telleman plus sucrose. The sucrose solution let us
      to isolate the cysts with less detritus. The cleaned cysts were splited in 3
      techniques to test the breaking: osmotic shock and heat, chemistry degradation
      and thermic shock, enzymatic action and mechanic effect. Only the last method was
      successful and showed bands in agarose gel. The result of this study shows a
      routine and common method which could be used in the previous steps to the PCR
      technique for the genotypification of these parasites.

PMID- 15559190
TI  - [Assessment of polymerase chain reaction (PCR) to diagnose brucellosis in a
      Brucella infected herd].
AB  - The diagnosis of bovine brucellosis using PCR in blood and milk samples from two
      dairy herds were compared to in vitro isolation, complement fixation test (CF),
      competitive ELISA (C-ELISA) in serum, and indirect ELISA (I-ELISA) in milk.
      Samples were obtained from 99 cows vaccinated with Brucella abortus strain 19,
      from a naturally infected herd (A), whose cows were also vaccinated with B.
      abortus strain RB51 as adults, and 100 from brucellosis free herd (B). In herd A,
      PCR identified 14 B. abortus infected cows: nine infected with wild type, and
      five with wild type and RB51, B. abortus S 19 was not identified. B. abortus
      biotype 1 was isolated from one cow. All cows infected with a wild strain of B.
      abortus were positive in serologic tests. Brucella was not found in herd B using
      PCR. Serological test showed 100% sensitivity related to PCR. The specificity for
      CF, C-ELISA and I-ELISA was 100%, 99% and 95% respectively. PCR could be useful
      to identify Brucella biotypes and to complement serologic tests.

PMID- 15559191
TI  - [Prevalence of Candida albicans and Candida non-albicans in clinical samples
      during 1999-2001].
AB  - The importance of epidemiological monitoring of yeasts involved in pathologic
      processes is unquestionable due to the increase of these infections over the last
      decade, the changes observed in species causing candidiasis, and empirical
      antifungal treatment. At the Mycology Center, 1006 isolates from a wide range of
      clinical samples were studied during 1999-2001. Candida albicans (40.3%) was the
      most isolated species, although, the Candida no albicans species with 54.9%
      showed the major prevalence. In blood cultures Candida parapsilosis (34.9%), C.
      albicans (30.2%) and C. tropicalis (25.6%) were recovered most frequently while
      C. glabrata represented only 2.3%. C. albicans with 60%-80% was the predominant
      specie in mucosal surface. We also detected Candida mediastinistis, which alert
      us over the importance at this location. Urinary tract infections caused by
      yeasts were more frequent in hospitalized patients, being C. albicans (47.7%),
      the most commonly isolated, followed by C. glabrata (24.8%) and C. tropicalis
      (20.0%). In the candidal onychomycoses, C. parapsilosis (37.7%) outplaced C.
      albicans (22.0%). Fluconazole susceptibility studies of Candida species allowed
      us to conclude that the majority of C. albicans islolates are susceptible, and
      that the highest resistance averages were observed in C. glabrata (21.41%) and C.
      krusei (69.23%).

PMID- 15559192
TI  - [Successful discontinuation of antifungal secondary prophylaxis in AIDS-related
      cryptococcosis].
AB  - The clinical and laboratory data of 22 patients with AIDS related cryptococcosis
      who were able to interrupt antifungal secondary prophylaxis after HAART
      administration, are presented. They were 14 males and 8 females, between 15 and
      50 years old (X: 34 years old). All patients presented fever and severe
      deterioration of their general health status, and 19 exhibited a meningeal
      syndrome. At the start of antifungal treatment, 59% of the cases presented < 50
      CD4+ cells/microl, the median viral burden was 134,804 RNA copies/ml and the
      median titer of serum cryptococcal antigen was 1/3,000. Amphotericin B by
      intravenous route, (0.7 mg/kg/day) or fluconazole (600 to 800 mg/day) were given
      as a treatment of the initial episode, up to CSF cultures negativization. Oral
      fluconazole (200 mg/day) or intravenous amphotericin B, 50 mg twice a week, were
      given as a secondary prophylaxis. The secondary prophylaxis was interrupted when
      the patients had received HAART for an average lapse of 19 months (6 to 36
      months) and the median CD4+ cell count was 249/microl. The follow up after
      secondary prophylaxis discontinuation lasted for a median lapse of 22 months.
      These data seem to show that secondary prophylaxis is not necessary when the
      patient are clinically asymptomatic and the CD4+ cell counts are above
      150/microl.

PMID- 15559193
TI  - [Pathological findings in pigs affected by the postweaning multisystemic wasting
      syndrome in Argentina].
AB  - Postweaning multisystemic wasting syndrome was first described in Canada in 1991
      and at present an increasing number of cases has been diagnosed worldwide. In
      Argentina the first cases of PMWS were reported recently. Forty eight 5 to 12
      week old pigs with signs characteristic of PMWS from 19 farms were studied.
      Although the real distribution of the virus in our country is not known it was
      observed an increasing number of farms with PMWS distributed in the major
      producing provinces. The histopathology was an important tool in diagnosis of
      suspicious cases of PMWS with the observation of different degrees of lesion. In
      the studied animals, the secondary infections, either by opportunistic pathogens
      or secondary bacteria could be important.

PMID- 15559194
TI  - [Sensitivity to colistin: evaluation of cut-off points available in disk
      diffusion test].
AB  - Infections produced by multidrug resistant organisms are one of the greatest
      problems in health centers. Often, only polymyxines show good activity "in vitro"
      against the carbapenem resistant gram-negative strains; but the National
      Committee for Clinical Laboratory Standards (NCCLS) documents do not currently
      provide interpretative criteria for testing the polymyxines. The antimicrobial
      activity of colistin, and the correlation between the agar dilution test and disk
      diffusion test were evaluated against 186 gram-negative strains isolated at the
      Hospital de Clinicas "Jose de San Martin" of Buenos Aires city. All
      susceptibility tests were performed according to the NCCLS recommendations. Were
      evaluated two breakpoints, NCCLS 1981 (< or = 8 mm and > or = 11 mm), and R.
      Jones 2001 (< or = 11 mm and > or = 14 mm). Discrepancies on interpretative
      category were found (0.5% minor; 2.2% major and 4.4% very major) with NCCLS 1981,
      and (18.9% minor; 3.8% major and 0.5% very major) with R. Jones 2001 criteria.
      Conclusions. In spite of the fact that the breakpoint used by R. Jones 2001
      decreases the very major error but increases the minor error, according to our
      results we recommend the use of MIC methods to assist the therapeutic application
      of colistin; however resistance to colistin was not detected with zone diameters
      > or = 16 mm.

PMID- 15559195
TI  - ["In vitro" activity of ten antimicrobial agents against anaerobic bacteria. A
      collaborative study, 1999-2002].
AB  - The antimicrobial activity of ampicillin, ampicillin-sulbactam, cefoxitin,
      ceftriaxone, imipenem, piperacillin, piperacillin-tazobactam, clindamycin,
      metronidazole, and azitromycin was assesed against 166 strains of anaerobic
      bacteria recovered from eight hospitals in Buenos Aires. The strains studied were
      Bacteroides fragilis group (65), Fusobacterium spp. (26), Prevotella spp. (21),
      Porphyromonas spp. (10), Clostridium difficile (10), other clostridia (12), and
      gram-positive cocci (22). The MICs were determined by the agar dilution method
      according to NCCLS document M11-A5. Metronidazole and piperacillin-tazobactam
      were the most active antimicrobial agents tested and exhibited MIC90 values of <
      or = 2 microg/ml and < or = 4 microg/ml against gram-negative organisms, and < or
      = 2 microg/ml, and < or = 8 microg/ml against gram-positive organisms,
      respectively. Among beta-lactams the activity against gram-negative rods was in
      the following order: imipenem > piperacillin > cefoxitin > ceftriaxone >
      ampicillin. Among the gram-positive bacteria the decreased activity was:
      piperacillin > imipenem > cefoxitin > ceftriaxone > ampicillin. The majority of
      the species studied showed different degrees of resistance to clindamycin and
      azitromycin. Nevertheless, 90% of Fusobacterium nucleatum and Porphyromonas spp.
      isolates were inhibited by 0.125 mg/ml of clindamycin and azitromycin,
      respectively.

PMID- 15559196
TI  - Virucidal activity presence in Trichilia glabra leaves.
AB  - Different immunomodulatory activities present in Trichilia glabra (TG) leaf
      extracts have already been described. Particularly, chloroform-methanol extracts
      were responsible for an in-vivo anti-inflammatory effect. The effect of such
      extracts on the infectivity of enveloped and naked viruses were investigated.
      Methanolic fraction extracts were active against herpes simplex virus type 1 (HSV
      1) and vesicular stomatitis virus (VSV), while no activity against poliovirus
      type 3 was observed. VSV was slightly more affected than HSV-1: 2.8 log10
      reduction in VSV titer against 2.4 log10 reduction in HSV-1 titer when 0.25 mg/ml
      F2 fraction was tested and a reduction of 2.7 log10 in VSV virus titer and of 1.5
      log10 in HSV-1 virus titer was observed when 0.25 mg/ml F3 fraction was tested.
      Results obtained in this work suggest a potential pharmaceutical use of TG
      extract components.

PMID- 15559197
TI  - [Microbiological study of dehydrated garlic (Allium sativum L.) and onion (Allium
      cepa L.)].
AB  - A microbiological study during the process and the storage of garlic (Allium
      sativum L.) and onion (Allium cepa L.) dehydrated, with the additional barriers
      of blanching or brine immersion, was made. In all raw materials the average
      counts of aerobic mesophilic bacteria expressed in CFU/g ranged from 1.2 x 10(2)
      to 1.6 x 10(3), molds and yeasts from 60 to 1.6 x 10(3), Lactobacillus spp. and
      Leuconostoc mesenteroides subsp. mesenteroides between 10 and 50. Microorganisms
      identified were Penicillium spp., Monilia spp., Lactobacillus brevis, Leuconostoc
      mesenteroides subsp. mesenteroides and yeasts in garlic; Mucor spp., Penicillium
      spp., Monilia spp., Lactobacillus brevis and yeasts in both types of onions.
      Leuconostoc mesenteroides subsp. mesenteroides was detected in only kind of
      onion. In dehydrated garlic storage, Penicillium spp., Monilia spp.,
      Lactobacillus brevis and yeasts were detected. In garlic, when a blanching step
      was carried out no microflora was detected. Mucor spp., Penicillium spp., Monilia
      spp. and Lactobacillus brevis were identified in both types of dehydrated onions.
      When brine immersion was included the microflora detected was significantly lower
      and only Penicillium spp. were found. The use of additional barriers such as
      blanching or brine immersion produces an important effect on the microbiological
      stability in these products.

PMID- 15559198
TI  - [Total bacterial count in raw milk from the dairy farms that characterize the
      zone northwest of Santa Fe and south of Santiago del Estero].
AB  - A total of 6,998 raw milk samples of bulk tank, belonging to 55 dairy farms
      associated to the Cooperativa Tambera Nueva Alpina Ltda., were collected between
      the years 1993 and 2002. The Total Mesophilic Aerobic Microorganisms Count was
      analyzed, obtaining a medium value of 1.2 x 10(5) +/- 2.4 x 10(5) CFU/ml that
      characterizes the zone. The final year of experience, observed a 97% of dairy
      farms evaluated with averages < or = 1.0 x 10(5) CFU/ml. Only a 3% it surpasses
      this limit, not being found establishments with levels over 1.5 x 10(5) CFU/ml.
      Relating this indicators with compositionals parameters, the most significant
      correlation resulted for: Total Bacterial Count vs Acidity (r = 0.292; P < 0.001)
      and Total Bacterial Count vs Freezing Point (r = 0.157; P < 0.001. The
      microbiological quality in raw milk of dairy farms belonging to the northwest
      zone of Santa Fe and south of Santiago del Estero showed a significant
      improvement during this time.

PMID- 15559199
TI  - [Distractions in pediatric surgery].

PMID- 15559200
TI  - [Epidermoid splenic cyst--state of the art].
AB  - In order to understand the features of splenic epidermoid cysts and their
      possible associated complications, four cases of splenic epidermoid cyst are
      presented in this report, two in children, one of them appeared in a child
      affected by a EBV and BH sepsis complicated with splenic abscesses due to scratch
      cat disease. The other two cases were adults. According to our histophatological
      findings, the pathogenesis may be related to a citodiferentation from mesothelium
      to squamous metaplasia. Our current knowledge about the role of spleen on
      immunological activity, mainly against capsulated germs, and the increase risk of
      overwhelming postesplenectomy septicemia have contributed to our conservative
      attitude about splenic surgery. We believe that management during the neonatal
      period should be conservative because cysts tend to disappear in most cases. In
      older children with a small cyst our recommendation is punction-aspiration and
      sclerotherapy, with ultrasound follow-up control.

PMID- 15559201
TI  - [Congenital sternal cleft].
AB  - INTRODUCTION: Congenital sternal cleft is a rare malformation. Little more than
      one hundred cases have been published, and rarely more than two cases are
      published in a single publication. We present five new cases that show the entire
      spectrum of defects. METHODS: They were 3 males and 2 females. Age range between
      1 day and 5 years of age. There were 2 supraxiphoid clefts (SC), 2 gladiolar
      defects and 1 xiphoid cleft. We evaluate the demographics, associated
      malformations, mode of treatments and results. RESULTS: The SC were not
      associated to congenital herat malformations, but with a many other malformative
      spectrum (anterior cervical web, hemangiomatosis, CNS malformations, coloboma and
      pectus excavatum). The two females had SC and were operated on the 24th and 30th
      days of age. The first one developed a superior vena cava sindrome for a few days
      after surgery and a moderate pectus excavatum that did not required surgery. A
      midline cervical web was also surgically repaired at 10 years of age. The second
      patient with SC was treated with interferon alfa-2a and local infiltration of
      corticosteroid for treatment of hemangiomatosis. Both patients had excellent
      final results (follow up 11 and 5 years respectively). Gladiolar clefts were
      observed durign surgical repair of congenital Herat malformations (ventricular
      septal defect and partial anomalous of pulmonary venous draninage). They were
      repaired by direct closure of the defect. The patient with the xiphoid cleft had
      associaed a Cantrell pentalogy. He died 4 days after operation because of extreme
      prematurity and pulmonary vascular hypertenion. CONCLUSIONS: 1) We have observed
      five new cases of sternal cleft. 2) Each anatomical variety had their own mode of
      presentation, a different malformative spectrum and clinical evolution that are
      based on a distinct embryonic origin. 3) Excluding the xiphoid clefts, the long
      term surviving is 100%, but they are associated with a great variety of other
      congenital defects.

PMID- 15559202
TI  - [Cleft palate and cleft lip. Clinical review].
AB  - The aim of this study is to do an analytical study of cleft palate and cleft lip
      in our hospital. PATIENTS AND METHODS: 85 clinical charts of patients attended in
      our hospital born between 1976 and 2001 in Aragon and Rioja were reviewed. We
      studied the incidence of oral cleft, associated malformations and morbidity,
      familial antecedents and perinatal data, phonatory disfunctions, serose otitis,
      growth failure and psychiatry problems. RESULTS: The mean incidence was 0.5/1000
      newborns. 41.5% presented associated malformations and 19.3% were associated with
      a specific syndrome, being more frequent in patients affected of cleft palate and
      cleft lip (50%) than patients with only cleft palate (41.2%) or only cleft lip
      (8.8%). The most frequent malformations were: facial defects (50%), skeletal
      (33%), congenital cardiopathies (33%). 19% were born prematurely. The percentage
      of serose otitis that required control at hospital was 37.3%. 34.2% presented
      phonatory problems. There was a high incidence of growth failure and psychiatry
      problems. CONCLUSION: Oral clefts represent a complex clinical condition with a
      high percentage of medical complications that require a multidisciplinary
      treatment. The high incidence of congenital defects associated with this
      condition demand an exhaustive screening in the newborns affected.

PMID- 15559203
TI  - [Lipoblastoma: the least well known of adipose tumors].
AB  - INTRODUCTION: Lipoblastoma is the least known of adipose tumours. It comes from
      embryonic adipose tissue and though it is histologically benign, it is locally
      invasive, implying a high risk of relapse if it is incompletely removed. The
      pediatric surgeon should be familiar with this tumor since it usually appears in
      children under three. MATERIAL AND METHODS: A retrospective study of the patients
      who were operated upon at our institution with a histologic diagnosis of
      lipoblastoma from 1966 to 2002 taking into account: age, tumor site, cytogenetic
      studies, first diagnosis, treatment and clinical course. RESULTS: The diagnosis
      of lipoblastoma was carried out in six patients (three boys and three girls). All
      were diagnosed before the first year of life and one was present at birth. In
      only one case the diagnosis was pre-operative. Two tumors were thoracic, two
      paravertebral with an intrarachidian component without spinal cord involvement
      (one of them was associated with myelomeningocele and diatomyelia), two in limbs
      and one perineal. A girl operated for the first time at four months, was latter
      operated in four opportunities for a relapse. In the last operation the excision
      was incomplete due to a subclavian involvement; in the last 15 years no new tumor
      growth was seen. After a follow-up period of 1 to 25 years in the other six
      patients no relapse was observed. CONCLUSIONS: Despite its low frequency, the
      diagnosis of lipoblastoma must be considered in children with masses in soft
      tissue, mainly if they are younger then one year. Because the lipoblastoma is
      locally invasive, this tumor must be treated before it affects viscera. The
      resection must be complete, avoiding the risk of relapse, although radical
      mutilating surgery is not recommended.

PMID- 15559204
TI  - [Evolution of pre and postoperative renographic parameters in pyeloreteral
      juntion obstruction syndrome].
AB  - With the objective of observing the modifications that the postoperative Diuretic
      Renography (DR) curve shows and determining how the quantitative parameters of
      this exploration (Differential Renal Function (DRF), Peak Time (PT), Half Time
      (HT), descent of maximum activity at 10 min (DMA10)) can be modified, the records
      of 50 patients affected by unilateral pyeloureteral junction obstruction and
      without any other associated pathology treated between 1991 and 2001, were
      revised. The age of the patients was between 1 month and 12 years (average 2
      years 7 months). Of the 50 patients, 31 were male and in 28 of the cases were
      affected on the left side. Patient selection was random. The preoperative
      evaluation was made using ultrasound (US), intravenous urography (IU), voiding
      cystourethrography (VCU), and RD. The RD technique and surgical intervention were
      standardized and the latter were performed by the same surgeon. Postoperative
      control was made with US and/or IU and RD between 6 and 18 months following
      surgery, even though total follow up ranged from 6 months to 10 years (average
      38.24 months). In all of the cases the follow up US and/or IU results were
      satisfactory, even though there was residual pyelic ectasia and absence of
      tension. The morphology of the preoperative curves was mostly obstructive or
      partially obstructive without lasix response, the curves became normal in 9 cases
      and partially obstructive with a good response to lasix in 38. The 3 remaining
      cases that corresponded to the hypofunctional kidney curve did not change. The
      DRF did not present major variations. The postoperative PT decreased in 62% of
      the cases. The HT and DMA10 improved in very few cases. In conclusion, it can be
      said that in spite of a good surgical outcome, the patterns of the postoperative
      renographic curve often do not completely normalize, major variations in the
      postoperative DRF are not expected, and with a diminshed postoperative PT a
      favorable pyeloplasty outcome can be appreciated. HT and DMA10 indicate
      improvement when they decrease, but do not indicate that the disease has
      reappeared when they do not change or increase.

PMID- 15559205
TI  - [Prognostic value of the ultrasound visualization of the bulging agent after
      endoscopic treatment of vesicouretal reflux].
AB  - INTRODUCTION: The endoscopic treatment of vesicoureteral reflux constitutes an
      easy and simple option at the moment for its resolution in all degrees and ages.
      It is necessary to carry out an ECO and VCUG (vesical cystouretrography) during
      voiding to verify their resolution. The ultrasongraphy can detect the wheal of
      injected material (Teflon or Macroplastic), but it is ignored if its
      visualization implies its disappearance or not. OBJECTIVE: To see the
      correspondence or not between the sonographic presence of injected material wheal
      and disappearance of reflux in the VCUG. MATERIAL AND METHODS: It has been
      statistically selected a sample of convenience to calculate the sensibility and
      specificity of the sonographic visualization of the endoscopic injected material
      wheal. We have studied 115 ureters with all the reflux degrees and ages, chosen
      randomly among patients treated endoscopically of vesicoureteral reflux,
      independently of the injected material, polytetrafluoroethylene (Teflon) or
      polydimethylsiloxane (Macroplastic). Refluxes due to duplex systems and those in
      which there were doubts of their correct installation during endoscopy were
      rejected. Cases with two or more injections were rejected too. The ECO and
      corresponding cystographies were revised in the first control after treatment
      (three months later). With this data, a chart of 2X2 was built comparing the
      presence or not of wheal in the ECO with the presence or not of reflux in the
      VCUG. We calculate sensibility, specificity, PPV (positive predictive value) and
      NPV (negative predictive value) as well as the degree of agreement of both tests
      with the kappa index. RESULTS: In 115 ureteral units we visualized with ECO the
      wheal of injected material in 97 and not in 18 (16%). In those cases with
      visualized wheal, reflux disappeared in 59 (61%), and in 38 not (39%). In those
      cases where the wheal was not visualized, reflux disappeared in 13 and persisted
      in other 5 (28%). The degree of sensibility was 12%, the specificity 82%, the PPV
      22% and the NPV 61%. CONCLUSIONS: Attending to the low specificity and predictive
      values, the sonographic presence of material wheal doesn't indicate that the
      reflux has been corrected, as well as its absence doesn't reflect the presence of
      the same one, being always necessary to carry out a cystography for its
      diagnosis.

PMID- 15559206
TI  - [Laparoscopic splenectomy in pediatrics. Review of 72 cases].
AB  - Splenectomy in childhood is nearly always related to hematologic disorders such
      as hereditary spherocytosis, immune thrombocytopenic purpura, sickle cell anemia
      and others. In recent years, laparoscopic splenectomy evolved into a safe and
      effective procedure that requires less hospital stay, and benefits the patient
      with a best postoperative period and excellent cosmetic results. The authors
      reveal a 6 year experience in treating 72 children with different diseases that
      required laparoscopic splenectomy. After progressing in their training curve and
      with the acquisition of new technology for endoscopic thermocoagulation, the
      authors conclude that minimally invasive surgery is the procedure of choice for
      most surgical spleen diseases in children.

PMID- 15559207
TI  - [Experimental model of auxiliary heterotopic liver-intestinal transplantation].
AB  - In pigs, orthotopic liver-intestine transplantation (LITX) has high per operative
      morbidity and mortality. It is due to hemodynamic, coagulation and metabolism
      disorders during native liver hepatectomy (total hepatic vascular exclusion) and
      the postoperative diarrhea secondary to initial dysfunction of the graft and
      enterectomy of native intestine. To avoid those disturbances and to increase the
      survival, we have developed a porcine model of auxiliary heterotopic LITX. The
      allograft was harvested in-bloc, containing the liver, duodenum, pancreas, and
      jejunum. In the recipient, the liver and intestine were left intact. The
      allograft was implanted heterotopically, caudal to the native liver. Venous
      drainage was achieved with anastomosis of donor (D) to recipient (R) infrahepatic
      cava; and arterialization with anastomosis of D aortic conduit containing the
      celiac axis and SMA to infra-renal R aorta. The D jejunum was hooked-up to R
      jejunum. The experiment was performed in 16 animals without intraoperative
      deaths, hemodynamic stability and no blood requirements. Four animals were left
      alive 7 days with functioning grafts, suggesting the model viability.

PMID- 15559208
TI  - [Laparoscopic adrenalectomy for neuroblastoma in children].
AB  - Since 1992 when it was described the first laparoscopic adrenalectomy in adults,
      few references can be found about this technique in children in Literature, and
      less the number of them that makes reference to neuroblastoma. For that reason we
      think it is interesting to describe two recent patients operated on by
      laparoscopy of neuroblastoma, the first in the left side and the second in the
      right with very good results; being the most interesting fact a 48-hours period
      of postsurgical stay. As conclusion we think that it is an useful technique in
      Pediatric Surgery, it gives a very good exposure of the retroperitoneal area, it
      gives small scars that laparotomy, and it reduces the hospital stay, only we
      object that must pass more time to be sure that it is a good technique for
      malignancy.

PMID- 15559209
TI  - [Congenital extraluminal duodenal diverticulum].
AB  - Congenital extraluminal duodenal diverticula are extremely rare. They usually
      present as repeated crisis of abdominal pain and most of the times their
      diagnosis is accidental because laboratory test performed by other cause. We
      report a girl with relapse crisis of abdominal pain since 2 years, the laboratory
      and radiographic findings are displayed. It is noteworthy that this disease can
      be life threatening sometime, when an acute abdomen is developed. Conversely of
      criteria followed in adults, surgery is adviced in children even without
      symptoms, to avoid further risks.

PMID- 15559210
TI  - [Guided bone regeneration beneath titanium foils].
AB  - The aim of this study was to examine the clinical and histological bony healing
      process beneath titanium foils used for guided tissue regeneration as well as of
      the Frios Algipore graft which was applied with autologous bone. 66 sinus floor
      elevations were carried out and examined over a period of three years and eight
      months. A success rate of 64% was recorded with foil incorporation. Complications
      occurred in form of primary and secondary disturbances in the healing process
      caused by exposure of the foil. 12 of the 66 foils had to be removed early. In
      all but one case, the augmented bone material was macroscopically well integrated
      despite the loss of the foil. Primary stability of the inserted dental implants
      into the ossified augmented site after operations of the sinus maxillaris was
      reached in all cases with absence of post-operative complications, and in 94%
      when there was postoperative exposure of the membrane. Histologically, a thin
      layer of connective tissue poor in cells but rich in collagen fibers appeared
      underneath the titanium foil. This was followed by newly-formed bony tissue
      transforming into osseous lamella parallel to the membrane underneath the new
      periost. In 65 out of 66 cases a sufficient amount of stable bone was built up
      locally suggesting good bio-compatibility and barrier function. Further, the foil
      also provided mechanical rest and supporting function for the space underneath.
      However, the occurrence of healing complications in 36% of the cases showed a
      need to improve on the titanium foils.

PMID- 15559211
TI  - [Filling revision--possibilities and execution].
AB  - For the last years new techniques and materials have been developed and tested to
      make corrections or revisions of fillings, metallic and ceramic restorations
      possible, allowing a bond between these different surfaces with reasonable
      strength. Composite material is qualified as universal repair material. Cavities
      of composite and amalgam fillings have to be sandblasted intraorally with
      aluminum oxide powder. The pre-treatment and conditioning of enamel and dentin
      can be managed by conventional methods such as the total etch technique but they
      cannot produce adequate microretentive surfaces on metallic and ceramic
      restorations. Silica coating by intraoral sandblasting and silane application can
      stabilize a durable bond. Enamel and dentin are conditioned additionally by
      conventional methods. Durable success of repair does not depend on using the
      original filling material. Adhesive and composite, however, have to be
      customised. While sandblasting hygiene should be observed and preventive measures
      are obligatory.

PMID- 15559212
TI  - [Erosion caused by gastric reflux in children. Discussion of etiology, clinical
      appearance and therapy in two cases].
AB  - Dental erosion is a disease occurring not only in adults but also in children.
      Thereby, deciduous and permanent teeth are involved. The cause of these lesions
      is an extended acid exposure due to extrinsic or intrinsic factors. Unlike
      caries, the erosive process occurs without involving bacteria. Main reasons are
      extensive consumption of erosive (soft) drinks and foodstuffs or
      gastrooesophageal reflux with regurgitation of gastric acid into the oral cavity.
      Often, the first signs of this disease are erosive lesions of the teeth and
      therefore dentists have an important role in early diagnosis. Two clinical cases
      are presented and the clinical diagnosis, the course and possible systemic and
      local preventive and therapeutic measures are discussed. Patients suffering from
      erosion can be treated successfully if the correct diagnosis and adequate
      preventive and therapeutic measures are performed.

PMID- 15559213
TI  - [Halitosis--Part 1: epidemiology and pathogenesis].
AB  - From an epidemiologic perspective halitosis concerns a large section of the
      population. Reports from affected people go back to ancient times. The causes may
      be both oral and non-oral changes. Oral causes are predominantly the coat of the
      tongue as well as marginal periodontitis. The non-oral causes include disorders
      in the field of the ear, nose and throat specialist, some general disorders,
      several drugs, smoking, special nutritional habits as well as disorders in the
      gastro-intestinal tract. Psychosomatic causes play an important role. Bacterial
      decomposition processes are decisively responsible for the development of
      halitosis.The occurring volatile sulphur compounds increase the permeability of
      oral mucosa, for example for endotoxins, and damage the periodontal tissue.

PMID- 15559214
TI  - [What should the neurologist do for saving a part of patients from ischemic
      stroke?].
AB  - The article focuses on a potential of vascular surgery prevention of cerebral
      stroke. Indications for carotid endarterectomy, late results of surgical
      treatment and possible complications are considered. Preventive surgeries are
      concluded to be prominent and effective.

PMID- 15559215
TI  - [The results of the MATCH study evidence for advantages of Clopidogrel
      monotherapy as secondary prophylaxis in cerebrovascular pathology].
AB  - A multicenter randomized double-blind placebo-controlled clinical trial The
      Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH)
      with Transient Ischemic Attack (TIA) or Ischemic Stroke (IS) studied efficacy and
      safety of a co-medication with acetylsalicylic acid (ASA) and Clopidogrel in
      comparison with a Clopidogrel monotherapy. It is shown that an addition of ASA to
      Clopidogrel therapy did not result in significant reduction of the risk of
      vascular events in patients with cerebrovascular pathology. But comparing to the
      placebo group, there was a significantly higher frequency of life-threatening
      bleedings [96 cases (2.6%) versus 49 (1.3%); p < 0.001] and pronounced bleedings
      [73 cases (1.9%) versus 22 (0.6%); p < 0.001] in the ASA receiving group.
      Therefore, the results of the MATCH trial demonstrated that ASA did not have any
      additional benefits while added to Clopidogrel it essentially raised a number of
      side effects.

PMID- 15559216
TI  - [Cerebral embolia in patients with prosthetic mechanic heart valves].
AB  - The review focuses on embolia of cerebral vessels in patients with prosthetic
      mechanic heart valves. The highest risk for embolia is observed in the first 3
      months after the surgery, a frequency of embolia being dependent on the type and
      position of the artificial valve. Methods for prevention of post-surgery
      thromboembolic complications are considered.

PMID- 15559217
TI  - [Cognitive disturbances in cerebellum infarctions].
AB  - The influence of the cerebellum on cognitive functions (CF) is poorly known and
      understudied so far. Neurological, neuropsychological and neuroimaging non
      randomized study was carried out in 25 patients (14 women, 11 men, mean age 51.8
      +/- 18.0 years) with isolated cerebellum infarctions. Cognitive disturbances (CD)
      were detected in 22 (88%) patients. They included impairment of attention,
      planning, control, abstract reasoning, memory; speech (naming, fluency,
      agrammatism, dysprosodia), special visual, quasi-spatial and counting disorders
      that indicated dysfunction of the anterior and posterior associative areas of the
      brain cortex. The expression of CD was different: being clinically obvious in 6
      patients (24%), they were found only by neuropsychological methods in 16 patients
      (64%). Clinically significant CD developed in the lesions of certain areas
      (posterior-lower- lateral and posterior-medial) of the cerebellum hemisphere
      related to the dominant brain hemisphere. The presence of these CD did not depend
      on infarctions size: in expressed CD it was smaller (mean 5.65 cm3) than in other
      cases (mean 12.8 cm3). Typical appearances of cerebellum infarction (ataxia,
      vertigo, vomiting) were observed in all the patients with clinically non
      significant CD and only in 2 out of 6 with clinically significant CD. The study
      demonstrated a role of the cerebellum in CF modulation. The expression of CD in
      cerebellum infarctions depends on their localization. Topic localization of the
      cerebellum areas, controlling CD and movement, is different.

PMID- 15559218
TI  - [Ischemic stroke in children].
AB  - Acute cerebral vascular pathology is considered to be an actual problem not only
      for adults but also for children. The data have been accumulating about a serious
      and non-rare brain disorder, namely acute disturbance of brain circulation,
      ischemic type. The long existed conception of a predominant role of intra
      cerebral hemorrhages in children has also been changed that mirrored in world
      publications of the last years, mostly devoted to the problem of ischemic stroke.

PMID- 15559219
TI  - [Clinical and pathogenetical features of ischemic stroke of young age].
AB  - A clinico-instrumental study of 78 young patients (mean age 41.3 +/- 4.2 years)
      with ischemic stroke was carried out. A prevalence of such risk factors as severe
      arterial hypertension, innate and acquired heart valvular disease, familial
      loading were characteristic of these patients, while ischemic heart disease and
      diabetes mellitus occurred less often. Comparing to elderly patients, no
      significant differences in dynamics of neurological deficit were found in young
      patients with ischemic stroke. The data of neuroimaging examination indicated
      less frequency of the signs of cerebral atrophy and leucoareosis in young
      patients. The results obtained confirm the presence of modifying risk factors for
      ischemic stroke in young patients that grounds realization of preventive
      measures.

PMID- 15559220
TI  - [Clinical and pathogenetical peculiarities and treatment policy in ischemic
      stroke of elderly and old age].
AB  - The data on randomized study of 2 groups of patients with ischemic brain
      hemisphere stroke of elderly and old (over 70 years) as well as middle (under 60
      years) age are presented. In elderly and old age, stroke develops on the basis of
      common affection of major vessels, with a great role of the "steal syndrome" in
      its pathogenesis. In authors' opinion, in treatment of ischemic stroke of elderly
      and old age attention should be paid to metabolic therapy, in particular to using
      high dosages of Cerebrolysin. Basing on clinical and paraclinical study, efficacy
      of this medication is revealed.

PMID- 15559221
TI  - [Falls in early in-patient rehabilitation of stroke patients].
AB  - Early in-patient rehabilitation is a basis for functional state improvement in
      patients with cerebral stroke (CS). The influence of the falls on the efficacy of
      early in-patient stroke rehabilitation is demonstrated. The incidence of falls
      among the patients with concomitant complications was 35.6%, in 3.4% of them hip
      fracture being observed. Patients with disturbances of orientation, coordination
      and mental abilities, especially in the cases of right hemisphere lesions, fall
      more frequently because of inadequate- or over estimation of their abilities. In
      this group, the indices of rehabilitation efficacy were lower that allowed to
      highlight the problem of falls in the patients with cerebral stroke at the early
      in-patient stage of rehabilitation.

PMID- 15559222
TI  - [A randomized, double-blind, placebo-controlled study of Cerebrolysin safety and
      efficacy in the treatment of acute ischemic stroke].
AB  - The aim of the study was to assess safety and efficacy of the neuroprotective
      drug Cerebrolysin in acute ischemic stroke. Thirty-six patients with ischemic
      stroke in carotid artery territory aged 45-85 years, were eligible for inclusion
      in the trial if they were admitted to the hospital within the first 12h after
      stroke onset. Patients were randomly and blindly assigned to placebo (n = 12) or
      1 or 2 dosages of Cerebrolysin: 10 ml/d (n = 12) and 50 ml/d (n = 12) for 10 days
      with concomitant standard basic treatment in each group. A quantitative time
      related analysis of the dynamics of neurological deficit revealed the tendency
      towards acceleration of improvement assessed by the Clinical Global Impression
      Scale and NIHSS in both Cerebrolysin groups by 30 day of the treatment. The
      significant reduction in the volume of MRI ischemic focus was shown in both
      Cerebrolysin groups (p < 0.05 vs Placebo) on day 3. Acute pharmacological test
      revealed a decrease (p < 0.05 vs Placebo) of the size and spread of delta and
      theta foci in 72.7% patients, receiving 50 ml/d of Cerebrolysin. In none of the
      cases, Cerebrolysin treatment provoked any paroxysmal activity on EEG. The trial
      demonstrated safety, efficacy and good tolerability of hige-dose Cerebrolysin in
      the treatment of ischemic stroke.

PMID- 15559223
TI  - [Atherogenic changes of blood lipids and their components in patients after
      ischemic stroke].
AB  - The aim of the study is to analyze frequency and character of blood lipids
      abnormalities in patients after ischemic stroke (IS). Blood lipids were studied
      in 54 patients who survived ischemic stroke at 38-70 years. Atherogenic
      dyslipidemia was found in 49 (90.7%) patients, 37% had a selective low level of
      HDL cholesterol (< 37 mg/dl). Patients with dyslipidemia, IV type, (27.8%) showed
      a high level of triglycerides (413 +/- 72mg/dl) and patients with IIa or IIb
      types--LDLP cholesterol (223 +/- 12.5 mg/dl). A complete analysis of blood lipids
      allows detecting atherogenic dislipedimia in the majority of patients who
      survived ischemic stroke (90.7%), which can be treated with statins or fibrates.
      An adequate therapy of such patients may significantly improve prognosis for
      those who survived ischemic stroke and, in some cases, prevent its development.

PMID- 15559224
TI  - [Monoclonal antibodies CD95 in an acute period of ishemic stroke in arterial
      hypertension].
AB  - The data on examination of 83 patients in acute period of cerebral stroke caused
      by arterial hypertension and 30 healthy controls are presented. In all the
      patients, content of Fas expressed lymphocytes (CD95), indirectly suggesting
      apoptosis, has been determined. The level of Fas/Apo-1+ lymphocytes was
      significantly higher comparing to the control group. Cerebral stroke severity
      positively correlated with Fas/Apo-1+ lymphocytes. The higher was a level of
      monoclonal antibodies CD95, the poorer was the course and prognosis both for
      recovering and for life. This correlation argues for a role of Fas/Apo-1+
      lymphocytes in the apoptotic process, and the level of their expression reflects
      that of apoptosis in damaged brain tissue and serves as a sign of immune
      inflammation in response to acute cerebral disaster.

PMID- 15559225
TI  - [A comparative analysis of organization of care for patients with stroke in
      Russia, Europe and the United States].
AB  - Studies of the systems of medical care for patients with acute disorders of brain
      circulation indicate that well-organized "stroke" service promotes morbidity
      decrease, lowers neurological deficit expression and restriction of social and
      daily activities. At the same time, there are essential differences in the scope
      of the medical care, which a patient can receive in different countries and no
      consensus on the most optimal system of medical scope for patients with stroke at
      different stages. The recent statistical reviews confirm that a patient admitted
      to specialized stroke departments has a less chance to die or to be a handicap.
      The article analyzes current systems service for patients with acute disorders of
      brain blood circulation in the United States, Europe and Russia.

PMID- 15559226
TI  - [Stroke epidemiology and evaluation of risk factors significance for survival of
      patients during 28 poststroke days in the open population of Chita].
AB  - To provide effective primary and secondary stroke prevention, the epidemiological
      stroke rates were investigated in the open population of a large Transbaykal town
      by the register method. During one year, 989 cases have been examined in the
      population aged above 25 years. The age-standardized stroke incidence rate (per
      100 000 persons) was 300 in women and 329 in men. The age-standardized stroke
      morbidity (per 100 000 persons) was 390 in women and 409 in men. Stroke mortality
      was 77 in women and 81 in men per 100 000 (p = 0.01). The stroke mortality in men
      was higher than in women. Stroke case fatality was 20% in men and 16% in women.
      The prevalence and significance of the main cardiovascular risk factors were
      revealed among patients by case-control study. Hypertension, psychological and
      social risk factors were the most significant in Chita's population of stroke
      patients.

PMID- 15559227
TI  - [Physical abuse of women].
AB  - OBJECTIVE: Our aim was determine prevalence of intrafamily violence of the type
      physical-abuse, toward female claimants aged 18 years and older at the HGZ MF No.
      1 in Colima. MATERIAL AND METHOD: A transversal study was conducted in 288
      females aged 18 years and older who were seen at the Family Medicine Unit for
      external consultation. RESULTS: Average age was 33.86 years (+/- 11.6), the
      highest level of schooling was primary for 33% of subjects and secondary for 26%,
      75% of our female claimants were divorced, 53.5% of monthly family incomes in
      each household was between 1,000 and 3,000 thousand Mexican pesos, and 27.8% of
      physical abuse consisted of shoving. CONCLUSIONS: Our research revealed that
      there is indeed physical violence toward 63.45% of female claimants at our
      hospital, especially toward those with low level of schooling, low socioeconomic
      status, and monthly income below minimum wage. These conditions only contribute
      toward making women fall prey to physical violence. Our study is only a first
      step for better understanding of domestic violence. Risk factors associated with
      physical abuse need to be controlled to decrease rate of interfamily violence
      against our claimants.

PMID- 15559228
TI  - [Laryngomalacia in a follow-up of a child development cohort for antecedents of
      perinatal encephalopathy. Implications for nosologic conceptualization].
AB  - We conducted a retrospective analysis of 10 cases of congenital laryngeal
      stridor. Reports of laryngeal endoscopy and diagnosis define laryngomalacia as
      laryngeal flaccidity and stridor. Some authors postulate that in addition to
      immaturity of cartilage, there exist the possibility of laryngeal uncoordination
      and dyskinesia. They support this idea in cases of late presentation,
      neurological damage, and atypical cases related with functional state or
      anesthesia. Laryngeal endoscopies were carried out in 10 cases included in a
      cohort of subjects from a longitudinal follow-up diagnosed with neurologica
      damage of perinatal origin. One case was diagnosed with postoperative unilateral
      paralysis of vocal chord and another identified vascular ring. The eight
      remaining cases fulfilled laryngomalacia criteria of diagnosis, but because of
      their characteristics origin is not an anatomic alteration but a functional
      hypotonia. The need to carry out an integral study to describe co-morbidity is
      emphasized.

PMID- 15559229
TI  - [Cholesterol goal attainment with lipid lowering drugs. The COMETA Mexico Trial].
AB  - In a retrospective study to determine rate of patients attaining therapeutic LDL
      C goal values with lipid-lowering drugs, 20 specialists and general practitioners
      were selected who enrolled 120 patients whose lipids were measured after at least
      12 weeks of treatment. They were grouped in three categories: group A (absolute
      risk of CHD in 10 years <10%); group B, with 10-20% risk, and group C, with >20%
      risk. Goal LDL-C values were <160 mg/dL for group A, <130 for group B, and <100
      for group C. Mean age was 57 +/- 12 years, 59% were males, and 51% were in group
      C; 83% took statins, 12% fibrates alone, and 5%, combinations. Atorvastatin and
      simvastatin were the most used drugs, at medium doses (mean 12 and 27 mg/day).
      LDL-C was reduced 25%; overall, 22% of patient doses were adjusted. Therapeutic
      goals were attained in 29% with initial doses and 42% at the end of study. Goal
      values were better attained in groups with lower risk. No differences were
      noticed among distinct physician categories. Data show poor compliance with
      international guidelines and insufficient attainment of therapeutic goals.

PMID- 15559230
TI  - [Asphyxiation by suffocation and strangulation in children younger than 15 years
      of age].
AB  - OBJECTIVE: Our aim was to describe non-intentional strangulation or suffocation
      suffered by children under 15 years of age. METHODS: Records from the Medical
      Examiner's Office showed child death by non-intentional strangulation or
      suffocation from January 1, 1991 to December 31, 2001. RESULTS: A total of 44
      suffocations or non-intentional strangulations were registered. Overall mortality
      was 3.62/1,000,000 persons-year (27.57/1,000,000 in children < 1 year of age,
      1.94/1,000,000 in older children); 63.6% were males. Most frequent mechanisms
      included neck entrapment between bars 18.2%, facial obstruction by bed clothes
      15.9%, being covered by rubble, sand, or garbage 15.9%, strangulation by cord,
      chain, or strip 11.4%, and strangulation by dress or bed clothes 9.1%.
      CONCLUSIONS: Nearly all registered deaths could be prevented by education,
      supervision, or structural modifications. Strategies should also include
      obligatory standards for manufacturing and for warnings on labels.

PMID- 15559231
TI  - [Isolation and characterization of wild Sporothrix schenkii strains and
      investigation of sporototrichin reactors].
AB  - We conducted a study in the southern mountains of the Mexican State of Oaxaca
      that consisted of isolation of wild Sporothrix schenckii strains obtained from
      soil samples and investigation of positive reactors to skin test reaction with
      sprotrichin antigen. The study was conducted by means of recollection of soil
      samples and processing of these with dilution methods and fungal isolation in
      ordinary culture media Sabouraud simple Agar with and without antibiotics (SS,
      SA). Suspected strains underwent dimorphism, melanin formation, and virulence
      confirmation tests. Investigation of positive reactors to sporotrichin Y (yeast)
      was also conducted. Three supposed strains were identified due to their
      reproductive characteristics, melanin production, and virulence. In the
      community, 144 individuals were studied, of whom 6.25% were positive to
      sporotichin. Isolation of virulent strains of Sporothrix schenkii from nature
      (soil) and primoinfection of a percentage of the studied population were
      confirmed.

PMID- 15559232
TI  - [Usefulness of establishing diagnosis and severity of the most frequent signs and
      symptoms in preeclamptic patients].
AB  - OBJECTIVE: Our aim was to determine that signs and symptoms are tools in
      establishing diagnosis and severity of preeclampsia. MATERIALS AND METHODS: Our
      study design was prolective, comparative, cross-sectional for evaluation of
      diagnosis. Our sample included 408 patients. The study employed classification
      criteria of the American College of Obstetricians and Gynecologists. One blinded
      family physician interrogated and examined each patient. The sample included
      patients with recent diagnosis and without treatment. Patients with HELLP
      syndrome, eclampsia, and those in Intensive Care were excluded. Clinical signs
      evaluated included headache, Phosphenes, acuphenes, tinnitus, vomiting,
      epigastric pain, right hypochondrium pain, ecchymosis, hematomas,and
      hyperreactive reflexes. RESULTS: A total of 192 patients without preeclampsia, 63
      with mild, and 153 with severe preeclampsia were included. Clinical
      manifestations were absent in 60, 21 and 8% respectively of patients in each
      group. Presence of three or more signs or symptoms had sensitivity of 60% (CI95%
      53-67), specificity of 84% (CI95% 79-89), and positive likelihood ratio of 3.8
      and negative, 0.48. Most usefulness data for diagnosis of preeclampsia are
      hyperreactive reflexes, phosphenes, acuphenes, right hypochondrium pain, and
      epigastric pain. CONCLUSIONS: The symptoms and signs taken alone are tools for
      evaluation of severity but not for detection of preeclampsia. There is necessary
      to develop new way for it's diagnosis during prenatal care.

PMID- 15559233
TI  - [The future of medical investigation in Mexico].
AB  - The current situation of clinical research in Mexico is analyzed. The main
      findings are as follows: 10% of total number of researchers in Mexico are engaged
      in medical research; there is a highly centralized distribution in the Mexico
      City metropolitan area; there exists unequal academic development among
      disciplines, and there is an overwhelming number of researchers in public
      educational and health institutions. A substantial increase in medical
      publications during the last 15 years with reasonable citation impact was also
      found. Several urgent matters to attend were identified, such as financing
      problems, effect of health services descentralization completed in 1997, and the
      need to selectively support certain research areas such as accidents, mental
      health, addictions, geriatrics and chronic diseases.

PMID- 15559234
TI  - [Usefulness of positron tomography (PET) in lung cancer].
AB  - Lung carcinoma is one on the leading causes of death from cancer in all parts of
      the world. The frequency of this tumor is increasing; at present, accounts for
      approximately 25% of all cancer deaths. The majority of lung cancers are
      initially detected on chest radiographs, but many benign lesions have radiologic
      characteristics similar to malignant lesions. Computed tomography (CT) is most
      frequently used to provide additional anatomic and morphologic information on
      lesions, but it is limited in distinguishing between benign and malignant
      abnormalities. Fluorodeoxyglucose-Positron emission tomography (PET-FDG) imaging
      provides physiologic and metabolic information that characterizes lesions
      indeterminate by CT, is used clinically to-differentiate benign from malignant
      focal pulmonary abnormalities, to stage mediastinal and extrathoracic metastases,
      and to identify recurrence. It is the gold standard that define the therapeutic
      strategy.

PMID- 15559235
TI  - [Autologous bone marrow transplantation as a treatment for autoimmune disease:
      mechanisms and results].
AB  - Autoimmune diseases are characterized by immune response against self antigens.
      One of the current research interests in this field is oriented toward
      development of tolerance. One of the newest options in the search for tolerance
      is autologous bone marrow transplantation: a variant of bone marrow transplant in
      which the patient's own hematopoietic stem cells are reinfused after
      myeloablative therapy. The idea of using bone marrow transplant in treatment of
      autoimmune diseases derived from observing remission in autoimmune diseases in
      patients transplanted due to coexisting neoplastic disease. Although an isolated
      initial report of bone marrow transplant as treatment for autoimmune disease
      questioned the utility of this procedure, over all, results are encouraging. To
      compile information in a programmed and systematic manner, it is necessary to
      send more patients in all stages of immune diseases to specialized centers to be
      included in large multicenter randomized trials. In time, the role for this
      procedure in autoimmune diseases will become clear.

PMID- 15559236
TI  - [A thirty five year old male with campimetric defect and spinal cord
      alterations].

PMID- 15559237
TI  - [All-trans retinoic acid syndrome. Case report and a review of the literature].
AB  - We described a patient with acute promyelocytic leukemia (APL) who developed all
      trans retinoic acid syndrome (ATRAS) and reviewed the literature. ATRAS presents
      in patients with APL treated with all-trans retinoic acid (ATRA). It has an
      incidence from 5%-27% with mortality of 29%. It is secondary to ATRA effect on
      promyelocyte differentiation, which causes systemic inflammatory response
      syndrome, endothelium damage with increase in capillary permeability,
      microcirculation obstruction, and tissue infiltration. ATRAS clinical
      manifestations are fever, hypotension, respiratory, renal and hepatic
      insufficiency, lung infiltrates, pleural and pericardic effusion, and generalized
      edema. Treatment is based on ATRA suspension, support measures, and steroids.

PMID- 15559238
TI  - [Hemorrhagic adrenal pseudocyst: case report and a review of the literature].
AB  - Adrenal cysts are rare entities, and hemorrhagic pseudocysts are even less
      frequent. Generally, they are unsuspected during first patient evaluation and can
      suggest acute abdomen. We present the case of a hemorrhagic pseudocyst with
      sudden onset of abdominal pain and features compatible with acute appendicitis.

PMID- 15559239
TI  - [On the epistemological approaches to medicine].
AB  - The doctrine of correct reasoning was developed in the Western World as logic.
      This is an activity of the intellect that apparently began with Zeno of Elea,
      being formalized by Aristotle, and which received its name from the Stoic
      philosopher Chrysippus. It corresponds to the structure or anatomy of thought.
      Logic empiricism introduced systematic use of the logistic language into
      epistemology. The latter discipline designates the philosophy of science, i.e.,
      the critical foundation of its principles, hypotheses, methods, and results.
      Strictly speaking, it does not constitute an analysis of the scientific method,
      which is rather the object of methodology, nor anticipation or synthesis of
      scientific results. It can be considered that, concerning science, epistemology
      constitutes the second step with a primary activity. In other words, it is a
      reflection on science, considering the latter as an element to be respected and
      not as a domain to be ruled. Dr. Hermann Boerhaave was the first physician to
      challenge problems of an epistemologic character in a coherent and systematic
      manner (XVIII Century). Others followed him in this direction during the
      subsequent centuries. In the light of Popper's critical rationalism, construction
      of a medical instrument, conception of a therapeutic procedure, development of a
      useful model in biology or medicine could also be considered as epistemologic
      problems. The corresponding examples that follow are worthwhile mentioning: Riva
      Rocci's sphygmomanometer; metabolic therapeutics for ischemic heart disease, and
      elaboration of theoretical models. In turn, epistemology suggests that assessment
      of a fact, perceivable by the senses, is generally more difficult that
      elaboration of a hypothesis.

PMID- 15559240
TI  - [Colloidal cyst of the third ventricle].

PMID- 15559241
TI  - [Parasites and autoimmunity].

PMID- 15559242
TI  - [The best approach to treat prolactinoma].
AB  - The prolactinoma is the most frequent pituitary tumor; the clinical presentation
      in women is characterized by menstrual disorders, amenorrhea, galactorrhea and/or
      sterility; neurological symptoms are present only when the tumor exceeds the
      sella turcica which is exceptional. Prolactin levels over 100 ng/mL are usually
      diagnostic of prolactinoma, as long as there are no pregnancy and/or
      hypothyroidism. The first therapeutical option is dopamine agonist drugs, thus
      surgery has been practically eliminated. Dopaminergic drugs suppress both
      synthesis and prolactin secretion, which in turn restores the ovarian function
      and induces tumor shrinkage. In conclusion, dopamine agonists constitute the
      prolactinoma treatment; in addition drug withdrawal is followed by remission of
      prolactinoma activity. In men, the size of the prolactinoma is larger,
      macroprolactinoma which usually presents extrasellar extension accompanied of
      neurological and visual symptoms; however the prolactinoma exhibits a favorable
      response with dopaminergic drugs.

PMID- 15559243
TI  - [Admission ceremony for new academicians].

PMID- 15559244
TI  - [Importance of chimerism in medicine].

PMID- 15559245
TI  - Update on human alpha1-adrenoceptor subtype signaling and genomic organization.
AB  - Alpha1-adrenoceptors are G-protein-coupled receptors that bind catecholamines.
      Sixteen distinct human alpha1A-adrenoceptor isoforms have been identified from
      human tissues, including five full-length and 11 truncated versions. An updated
      scheme for the identification of alpha1A-adrenoceptor splice variants is
      proposed. Given the established roles of alpha1-adrenoceptors in benign prostatic
      hyperplasia, myocardial hypertrophy and other cardiovascular disorders,
      elucidation of the biological significance of the signaling diversity and
      potential pharmacological roles of alpha1A-adrenoceptor splice variants are
      important areas of future research.

PMID- 15559246
TI  - Sex and drug abuse: a role for retrograde endocannabinoids?

PMID- 15559247
TI  - Pharmacogenomics in cancer therapy: is host genome variability important?
AB  - Pharmacogenomics aims to elucidate the genomic determinants of drug disposition
      and effect. Because cancer chemotherapy is relatively nonspecific and has narrow
      therapeutic indices, there is great potential for pharmacogenomics to improve
      treatment outcomes by either reducing toxicity or increasing efficacy. The
      diversity of therapeutic targets for anticancer drugs and the intensity of
      clinical pharmacology research in oncology have provided many examples of
      clinically relevant pharmacogenomic applications. Important elements that are
      discussed in this article include the association of genetic variability in the
      metabolism, intracellular transport and targets of anticancer drugs. In addition,
      we summarize where the field stands currently, and how information from the host
      and tumor might be integrated into decision making.

PMID- 15559248
TI  - Targeting Ca2+ channels to treat pain: T-type versus N-type.
AB  - The transmission of pain signals at the spinal level is crucially dependent on
      voltage-gated Ca2+ channels in nociceptive neurons. Pharmacological and gene
      knockout studies implicate N-type Ca2+ channels as key mediators of nociceptive
      signaling in dorsal root ganglion (DRG) neurons, and as potential targets for the
      development of analgesic drugs. Furthermore, nociceptor-specific alternative
      splicing of the gene encoding N-type Ca2+ channels might provide strategies for
      splice-isoform-specific drug targeting. More recently, T-type Ca2+ channels have
      been implicated in the processing of pain signals at both spinal and thalamic
      levels. However, although inhibition of T-type channel activity in DRG neurons
      mediates analgesia, gene knockout of T-type channels in the CNS is reported to
      increase the perception of visceral pain. In this review, we discuss the
      implications of these findings for the design of novel therapeutic strategies and
      contrast the role of T-type channels with that of N-type channels in pain
      transmission and analgesia.

PMID- 15559249
TI  - Pharmacological inhibitors of glycogen synthase kinase 3.
AB  - Three closely related forms of glycogen synthase kinase 3 (GSK-3alpha, GSK-3beta
      and GSK-3beta2) have a major role in Wnt and Hedgehog signaling pathways and
      regulate the cell-division cycle, stem-cell renewal and differentiation,
      apoptosis, circadian rhythm, transcription and insulin action. A large body of
      evidence supports speculation that pharmacological inhibitors of GSK-3 could be
      used to treat several diseases, including Alzheimer's disease and other
      neurodegenerative diseases, bipolar affective disorder, diabetes, and diseases
      caused by unicellular parasites that express GSK-3 homologues. The toxicity,
      associated side-effects and concerns regarding the absorption, distribution,
      metabolism and excretion of these inhibitors affect their clinical potential.
      More than 30 inhibitors of GSK-3 have been identified. Seven of these have been
      co-crystallized with GSK-3beta and all localize within the ATP-binding pocket of
      the enzyme. GSK-3, as part of a multi-protein complex that contains proteins such
      as axin, presenilin and beta-catenin, contains many additional target sites for
      specific modulation of its activity.

PMID- 15559250
TI  - Functional, molecular and pharmacological advances in 5-HT7 receptor research.
AB  - The 5-HT7 receptor was among a group of 5-HT receptors that were discovered using
      targeted cloning strategies 12 years ago. This receptor is a seven-transmembrane
      domain G-protein-coupled receptor that is positively linked to adenylyl cyclase.
      The distributions of 5-HT7 receptor mRNA, immunolabeling and radioligand binding
      exhibit strong similarities, with the highest receptor densities present in the
      thalamus and hypothalamus and significant densities present in the hippocampus
      and cortex. The recent availability of selective antagonists and knockout mice
      strains has dramatically increased our knowledge about this receptor. Together
      with unselective agonists, these new tools have helped to reveal the 5-HT7
      receptor distribution in more detail. Important functional roles for the 5-HT7
      receptor in thermoregulation, circadian rhythm, learning and memory, hippocampal
      signaling and sleep have also been established. Hypotheses driving current
      research indicate that this receptor might be involved in mood regulation,
      suggesting that the 5-HT7 receptor is a putative target in the treatment of
      depression.

PMID- 15559251
TI  - Molecular properties of ATP-gated P2X receptor ion channels.
AB  - P2X receptors for ATP are expressed throughout the body and mediate a multitude
      of functions, including muscle contraction, neuronal excitability and bone
      formation. In the mid-1990s seven genes encoding P2X receptors (P2X(1-7)) were
      identified. These receptors comprised a novel family of ligand-gated ion channels
      with subunits that possessed intracellular N- and C-termini, two transmembrane
      domains and an extracellular ligand-binding loop. No crystal structures are
      available for these channels. Furthermore, they are distinct from the nicotinic
      acetylcholine (Cys-loop) and glutamate families of ion channels and have no
      similarity to other ATP-binding proteins, thus precluding homology modelling
      based studies of their structural properties. However, molecular techniques have
      provided insight into the properties of P2X receptors: mutagenesis and
      biochemical studies have identified regions associated with ATP binding, ionic
      conduction, channel gating and regulation. In addition, transgenic approaches
      have helped to characterize the role of defined receptor subunits in native
      systems.

PMID- 15559252
TI  - Techniques: Bioprospecting historical herbal texts by hunting for new leads in
      old tomes.
AB  - Ethnobotany has led to the identification of novel pharmacological agents but
      many challenges to using ethnobotany as a research tool remain. In particular,
      the loss of traditional knowledge together with the advent of high-throughput
      screening has made ethnobotanical techniques laborious and potentially
      unnecessary. However, historical herbal texts provide a preexisting resource that
      documents the traditional uses of various species as medicines. As generational
      losses of traditional knowledge accrue, these herbal texts become increasingly
      valuable. The methodology for extracting useful information contained within
      these resources had been cumbersome and consuming. However, the application of
      new bioinformatics data-mining systems to herbal texts holds great promise for
      identifying novel pharmacotherapeutic leads for bioactive compounds.

PMID- 15559253
TI  - Techniques: Use of concatenated subunits for the study of ligand-gated ion
      channels.
AB  - Members of the pentameric ligand-gated ion channel family, comprising GABA(A)
      receptors, nicotinic acetylcholine receptors, glycine receptors and 5-HT3
      receptors, are involved in information transfer at both synapses and the
      neuromuscular junction. However, receptors that are composed of five subunits are
      difficult to analyse by recombinant expression of a mixture of the single
      subunits because multiple receptor subtypes with different subunit composition or
      arrangement can be formed. Covalently linking the C-terminus of the preceding
      subunit with the N-terminus of the following subunit to form a concatenated
      subunit enables the precise predetermination of subunit arrangement in these
      receptors. A forced subunit assembly enables the characterization of: (i)
      receptor architecture; (ii) properties of receptors that contain different
      subunit isoforms in specific locations; and (iii) selective introduction of a
      mutation into a specific subunit that occurs multiple times in a receptor. Thus,
      this method also facilitates the investigation of positional effects of mutations
      associated with diseases.

PMID- 15559254
TI  - Protecting the next generation: ANA, nursing partners work to educate students on
      safe patient handling techniques.

PMID- 15559256
TI  - President's column: a passion for workplace advocacy.

PMID- 15559258
TI  - Tuning in to nurses on Nurseradio.org.

PMID- 15559259
TI  - Trends in physiologic monitoring systems: the old and the new.

PMID- 15559260
TI  - Alarm-enhancement systems for ventilators: problems with physiologic monitoring
      interfaces.
AB  - In our January 2004 Guidance Article "Alarm-Enhancement Systems for Ventilators,"
      we discussed several categories of ventilator alarm enhancements that communicate
      ventilator alarms to locations where they are more likely to be detected by
      caregivers. One of these options is interfacing ventilators with networked
      physiologic monitors. Presently, as part of an Evaluation we are conducting on
      physiologic monitoring systems, we are testing interfaces that allow ventilator
      alarm notification at a monitoring system's central station. While such
      interfaces can offer considerable advantages, our testing has also revealed some
      problems. These problems are not severe enough to rule out the monitoring
      interface option, but they are significant, and hospitals need to be aware of
      them.

PMID- 15559261
TI  - Digital image storage.
AB  - Film has long been considered the gold standard for displaying and storing
      clinical images. But that may be changing. Digital technology--specifically
      digital imaging and storage technology--has advanced to the point where it can
      now deliver on the promises envisioned years ago. That is, the ability to provide
      any image, virtually anywhere, at any time--a goal that could never be achieved
      with film. Achieving this goal, however, requires a properly implemented digital
      infrastructure, including effective digital image storage. As early adopters will
      attest, digital image storage can be difficult to implement. It requires the
      careful selection and implementation of storage technologies and the continuous
      management of storage operations. In this Guidance Article, we address many of
      the issues facing the healthcare professionals charged with managing this
      process: We introduce the topic of medical digital storage, discussing how it is
      accomplished and why storing images is not that different from storing other
      forms of data. We review the available storage alternatives, from fast-access
      hard drives and RAIDs to long-term magnetic tape and optical disc storage. We
      delve into the issue of image compression, describing what compression is and how
      much can be used without affecting patient care. And we review the pertinent
      legal, regulatory, and management issues. When committing to a digital image
      workflow, it is essential that a healthcare facility give careful consideration
      to data storage issues, since poor choices can lead to significant long-term
      costs for the facility.

PMID- 15559262
TI  - Heating of a cerebral oximeter's in-line amplifier illustrates that hot
      electronics in bed can burn patients.

PMID- 15559263
TI  - Reasons for imaging equipment lockups.

PMID- 15559264
TI  - Misalignment may lock up Siemens Axiom Artis X-ray systems.

PMID- 15559265
TI  - Role of black carbon in the partitioning and bioavailability of organic
      pollutants.

PMID- 15559266
TI  - Sorption of 2,4'-dichlorobiphenyl and fluoranthene to a marine sediment amended
      with different types of black carbon.
AB  - Recent studies demonstrate that sedimentary black carbon (BC) affects the
      sorption of some hydrophobic organic contaminants (HOCs) to a greater extent than
      sedimentary organic carbon (OC). Among HOC, polycyclic aromatic hydrocarbons
      (PAHs) are known to interact extensively with BC. Currently, data on the sorption
      of various kinds of HOCs to different types of BC are limited. In this study, we
      amended a marine sediment with BC from several different sources, humic acid, and
      inert sand. Equilibration studies with 14C fluoranthene and the polychlorinated
      biphenyl (PCB) 3H 2,4'-dichlorinated biphenyl were performed to determine the
      magnitude of sorption as a function of contaminant and BC type. The magnitude of
      sorption to the BC-amended sediments was greater for the PAH than the PCB as
      compared to the sediment alone, humic acid, and sand. For example, differences
      between the log partition coefficient (K(P)) for the PAH and PCB ranged from 0.41
      to 0.69 log units for humic acid and sand treatments, while differences ranged
      from 0.88 to 1.57 log units for the BC-amended sediments. As a result, BC
      normalized partition coefficients (log K(BC)) for the PAH averaged 6.41, whereas
      the PCB log K(BC) values averaged 5.33. These results demonstrate that PAH
      sorption and most likely bioavailability are influenced strongly by the presence
      of BC of different types, while sorption of a nonplanar PCB was affected to a
      lesser degree.

PMID- 15559267
TI  - Model verification of thermal programmed desorption-mass spectrometry for
      estimation of release energy values for polycyclic aromatic hydrocarbons on
      mineral sorbents.
AB  - The physical availability of organic compounds in soil and sediment strongly
      influences their bioavailability and toxicity. Previous work has indicated that
      physical availability changes throughout the processes of aging and treatment and
      that it can be linked to the energy required to release the compound from its
      sorbent matrix, with a higher energy indicating a more tightly bound compound.
      This study focused on determining release energy values for various mineral
      geosorbents (glass beads, sand, and kaolin) contaminated with a 16 polycyclic
      aromatic hydrocarbon (PAH) mixture. The sorbents were analyzed using thermal
      program desorption/mass spectrometry (TPD/MS) and the release energy values were
      calculated from the resulting thermograms utilizing a nonlinear fit of the
      analytical solution to a simplified version of the Polanyi-Wigner equation. This
      solution method resulted in a series of combinations of values for the pre
      exponential factor (v) and release energy (E) that produced desorption rate
      curves with similar errors when fit to actual data sets. These combinations can
      be viewed as an error surface, which clearly shows a valley of minimum error
      values spanning the range of both E and v. This indicates that this method may
      not provide a unique set of E- and v-values and suggests that the simplified
      version of the Polanyi-Wigner equation cannot be used to determine release energy
      based on TPD data alone.

PMID- 15559268
TI  - Dependency of polychlorinated biphenyl and polycyclic aromatic hydrocarbon
      bioaccumulation in Mya arenaria on both water column and sediment bed chemical
      activities.
AB  - The bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) and
      polychlorinated biphenyls (PCBs) by the filter-feeding soft-shell clam Mya
      arenaria was evaluated at three sites near Boston (MA, USA) by assessing the
      chemical activities of those hydrophobic organic compounds (HOCs) in the sediment
      bed, water column, and organisms. Polyethylene samplers were deployed to measure
      the activities of HOCs in the water column. Sediment activities were assessed by
      normalizing concentrations with sediment-water sorption coefficient values,
      including adsorption to black carbon in addition to absorption by organic carbon.
      Likewise, both lipids and proteins were considered in biota-water partition
      coefficients used to estimate chemical activities in the animals. Chemical
      activities of PAHs in M. arenaria were substantially less than those of the
      corresponding bed sediments in which they lived. In contrast, chemical activities
      of PCBs in M. arenaria often were greater than or equal to activities in the
      corresponding bed sediments. Activities of PAHs, such those of pyrene, in the
      water column were undersaturated relative to the sediment. However, some PCBs,
      such as congener 52, had higher activities in the water column than in the
      sediment. Tissue activities of pyrene generally were in between the sediment and
      water column activities, whereas activity of PCB congener 52 was nearest to water
      column activities. These results suggest that attempts to estimate
      bioaccumulation by benthic organisms should include interactions with both the
      bed sediment and the water column.

PMID- 15559269
TI  - Effects of sedimentary sootlike materials on bioaccumulation and sorption of
      polychlorinated biphenyls.
AB  - Bioaccumulation of hydrophobic organic chemicals from sediments containing soot
      or sootlike materials has been hypothesized to be limited by strong sorption of
      the chemicals to the soot matrixes. To test this hypothesis, we quantified
      bioaccumulation of 11 polychlorinated biphenyls (PCBs) into the aquatic
      oligochaete Limnodrilus sp. exposed to spiked sediment with and without the
      sootlike materials coal and charcoal. In addition, sorption experiments with
      sediment containing varying amounts of coal or charcoal were performed to
      elucidate the accumulation mechanism. Results showed that coal and charcoal (at
      realistic levels of 1.5% on a dry-wt basis) reduced PCB accumulation in worms 1.2
      to 8.5 times when expressed on a mass basis. Moreover, whereas bioaccumulation
      from pure sediment increased with molecular planarity of the PCBs (toxic
      potency), it decreased in case of sediments containing coal and charcoal. In
      contrast to this advantageous effect, it was hypothesized that coal and charcoal
      had an adverse influence on the habitat quality of oligochaetes: Organisms
      inhabiting sediment containing coal or charcoal had significantly reduced lipid
      contents as compared to organisms from pure sediment. Because of these reduced
      lipid contents, lipid-normalized PCB concentrations in worms and biota-to
      sediment accumulation factors (BSAFs) for most PCBs were higher in sediments
      containing the sootlike materials as compared to those for reference sediment.
      Also, measured BSAFs for coal- and charcoal-containing sediments appeared to be
      much higher than estimated on the basis of equilibrium partitioning theory.
      Sorption experiments revealed that this was caused by much weaker sorption to the
      sediment-coal/charcoal mixture than calculated assuming linear additivity of
      sorption capacities of the distinct phases. It was hypothesized that this weaker
      sorption resulted from competition between PCBs and dissolved organic carbon
      molecules for sorption sites on coal/charcoal. This points to a sorption process
      that is much more complicated than generally assumed.

PMID- 15559270
TI  - Influence of soot on hydrophobic organic contaminant desorption and assimilation
      efficiency.
AB  - Soot, soot-amended sediment, and unamended sediment spiked with hydrophobic
      organic contaminants (HOC) were subjected to laboratory desorption and
      assimilation efficiency experiments in an effort to assess and compare the
      importance of soot in controlling HOC desorption and deposit-feeder assimilation
      efficiency. Three contaminants, naphthalene (NAP), benzo[a]pyrene (BaP), and
      hexachlorobenzene (HCB) were sorbed to sediments, sediments amended with soot (2
      4% dry wt), and soot for a period of 34 d. Desorption of all three contaminants
      into seawater from the three prepared sorbates was then monitored, and Nereis
      succinea assimilation efficiency experiments on the BaP- and HCB-contaminated
      sorbates were conducted. Both NAP and BaP desorption rates for soot and soot
      amended sediments were reduced by at least a factor of two relative to unamended
      sediment. Hexachlorobenzene desorption rates were similar for both the soot
      amended and the unamended sediments. Results of N. succinea assimilation
      efficiency experiments indicate a trend similar to the desorption experiments:
      higher assimilation of BaP from unamended relative to soot-amended sediment and
      little difference in assimilation between treatments for HCB. However, soot was
      more effective in reducing BaP desorption than assimilation efficiency, which
      would be consistent with the hypothesis that the gut fluid dissolution by deposit
      feeders may partially decouple biological availability from chemical
      availability.

PMID- 15559271
TI  - Importance of black carbon in distribution and bioaccumulation models of
      polycyclic aromatic hydrocarbons in contaminated marine sediments.
AB  - The roles and relative importance of nonpyrogenic organic carbon (NPOC) and black
      carbon (BC) as binding phases of polycyclic aromatic hydrocarbons (PAHs) were
      assessed by their ability to estimate pore water concentrations and biological
      uptake in various marine sediments. Sediment bioaccumulation tests were performed
      with the marine polychaete Nereis virens, using a polyethylene device to estimate
      pore water concentrations of PAHs. Using existing partitioning data for pyrene
      and phenanthrene, it was found that the traditional Equilibrium Partitioning
      model, which assumes all organic carbon is NPOC (EqP(OC)), overestimated the
      measured pore water concentrations in the test sediments by one to three orders
      of magnitude. Instead, the measured pore water concentrations were better
      predicted from a distribution scenario that uses both BC and NPOC (EqP(NPOc,BC))
      When comparing actual worm body burdens of pyrene and phenanthrene with the two
      model estimates of worm tissue concentrations, the EqP(OC) model tended to
      overestimate actual body burdens by three orders of magnitude, while the
      EqP(NPOC,BC) model came much closer to the true body burden values. The observed
      distribution of PAHs in the test sediments was used to calculate BC partition
      coefficients for five PAHs, which were one to two orders of magnitude higher than
      their corresponding organic carbon-normalized distribution coefficients, or
      K(OC)s. Together, these results suggest that, in certain situations, adding black
      carbon to distribution models may be necessary to predict accurately the
      bioavailability of PAHs.

PMID- 15559272
TI  - Relationship between metabolism and bioaccumulation of benzo[a]pyrene in benthic
      invertebrates.
AB  - The potential influence of polycyclic aromatic hydrocarbon (PAH) metabolism on
      bioaccumulation is well accepted, but rarely has been examined in many species of
      benthic invertebrates that commonly are found in contaminated sediments, or used
      in bioaccumulation or toxicity tests. In this study, the relative ability of 11
      species of near-shore benthic invertebrates to metabolize and bioaccumulate a
      model PAH, benzo[a]pyrene (B[a]P), was evaluated. Species examined included six
      polychaetes (Clymenella torquata, Nereis virens, Nereis succinea, Nephtys incisa,
      Spio setosa and Cirriformia grandis), three bivalves, (Macoma balthica, Mya
      arenaria, and Mulinia lateralis), and two amphipods (Ampelisca abdita and
      Leptocheirus plumulosus). After 7 d of exposure to sediments spiked with
      radiolabeled B[a]P, metabolites comprised between 6.1% (Clymenella torquata) to
      85.7% (Nereis succinea) of total accumulated B[a]P, with individual species from
      the same phylogenetic groups showing large differences in their ability to
      metabolize this PAH. Bioaccumulation factors (B[a]P in tissue/B[a]P in sediment)
      were inversely related to the species' ability to metabolize PAH, highlighting
      the importance of considering metabolism when interpreting bioaccumulation across
      several species. These data argue strongly against the continued use of the large
      polychaete Nereis virens, one of the species showing the greatest ability to
      metabolize B[a]P, for bioaccumulation testing when PAHs are being considered.
      Other commonly used test species had relatively low levels of metabolism
      (Ampelisca abdita, Leptocheirus plumulosus, and Macoma balthica), supporting
      their use in evaluation of potential PAH impact on the environment.

PMID- 15559273
TI  - Influence of soot carbon on the bioaccumulation of sediment-bound polycyclic
      aromatic hydrocarbons by marine benthic invertebrates: an interspecies
      comparison.
AB  - The sorption of polycyclic aromatic hydrocarbons (PAHs) to soot carbon in marine
      sediments has been hypothesized to reduce PAH bioavailability. This hypothesis
      was tested for eight species of marine benthic invertebrates (four polychaete
      worms, Clymenella torquata, Nereis virens, Cirriformia grandis, and Pectinaria
      gouldii, and four bivalve mollusks, Macoma balthica, Mulinia lateralis, Yoldia
      limatula, and Mya arenaria) that span a wide range of feeding behavior, ability
      to metabolize PAHs, and gut chemistry. Organisms were exposed for 20 d to two PAH
      spiked sediments, one with soot and one without soot. The soot treatment
      generally resulted in lower bioaccumulation than the no soot treatment, though
      the differences between treatments were not significant for all species. All but
      one species accumulated significant PAH concentrations in their tissues from the
      soot treatment, indicating that soot-bound PAH cannot be dismissed as unavailable
      to infaunal benthic biota. Bioaccumulation factors were correlated negatively to
      both the organisms' ability to metabolize PAHs and the gut fluid contact angle,
      supporting the hypotheses that high PAH metabolism results in lower
      bioaccumulation factors and bioavailability of PAHs may be limited partially by
      PAH solubilization in the gut lumen. The variability in bioaccumulation due to
      the soot treatment was much less than the variability between species and between
      PAH analytes. Comparatively low bioaccumulation was observed in Nereis virens, a
      species commonly used in bioaccumulation tests. These results suggest that more
      effort is needed in understanding the salient characteristics of species present
      in a threatened environment, rather than focusing solely on the sediment
      geochemistry (e.g., soot and organic carbon content) and contaminant
      characteristics when predicting ecological risk of PAH-contaminated sediments.

PMID- 15559274
TI  - Role of source matrix in the bioavailability of polycyclic aromatic hydrocarbons
      to deposit-feeding benthic invertebrates.
AB  - The bioavailability of polycyclic aromatic hydrocarbons (PAHs) to benthic
      organisms is complicated by the variety of ways that they are introduced to
      coastal waters (dissolved, as nonaqueous phase liquids, and tightly bound to
      soot, coal, tire rubber, and eroded shale). In order to better understand the
      controlling variables that affect chemical and biological availability of PAHs, a
      study was conducted in which three deposit-feeding infaunal benthic invertebrate
      species (Cirriformia grandis, Clymenella torquata, and Macoma balthica) were
      exposed to sediments amended with PAH-rich materials (coal dust, tire rubber,
      diesel soot, creosote, crude oil, and fuel oil). Lipid and organic carbon
      normalized bioaccumulation factors (BAF(1oc)s) were calculated after 20 d of
      exposure and PAH bioavailability from the different treatments was assessed.
      Bioaccumulation of coal-derived PAHs usually was too low to be measured, though
      PAHs associated with soot and tire rubber showed significant accumulation in
      organism tissues. Polycyclic aromatic hydrocarbons from the fuel oil, creosote,
      and crude oil treatments were more bioavailable than PAHs bound in solid
      carbonaceous matrices (soot, coal, and tire rubber). Desorption of PAHs from the
      amended sediments into seawater also was measured using XAD resin. As was
      observed with bioaccumulation, PAHs in coal were desorbed the least; tire rubber
      and diesel soot were intermediate; and creosote, fuel oil, and crude oil desorbed
      to the greatest extent. In only one out of the three species evaluated was PAH
      bioaccumulation related to extent of desorption after 20 d. Decoupling between
      biological and chemical availability may be due to species-specific factors such
      as surfactant-mediated solubilization in the guts of some deposit-feeding
      organisms. A significant finding of this work was the demonstration that PAHs
      associated with soot and tire rubber in their native state (rather than
      experimentally added) are available to some benthic biota.

PMID- 15559275
TI  - Evaluation of the role of black carbon in attenuating bioaccumulation of
      polycyclic aromatic hydrocarbons from field-contaminated sediments.
AB  - The significance of black carbon (BC) for the bioavailability of polycyclic
      aromatic hydrocarbons (PAHs) was examined by using historically contaminated
      intact sediment cores in laboratory exposure experiments with the deposit-feeding
      amphipod Monoporeia affinis. Log values of amphipod biota-sediment accumulation
      factors (BSAFs) were significantly related to log BC, whereas log BSAFs were
      related to log octanol-water partition coefficients only in background sediments
      containing less BC. In the background sediments, the BSAF for polycyclic aromatic
      hydrocarbons (PAHs) was 1 to 2 for phenanthrene, with lower values for more
      hydrophobic PAHs, indicating an increase in nonequilibrium conditions with
      increasing PAH molecular size. For the near-equilibrated phenanthrene and
      fluoranthene, higher BSAFs were measured during exposure to background sediments,
      with BSAF decreasing to <0.1 in contaminated sediments in the Stockholm
      waterways. In situ caged mussels (Dreissena polymorpha) exhibited field BSAF
      values (relative to sediment-trap-collected suspended matter) for polychlorinated
      biphenyls (PCBs) of 0.1 to 0.4, but for PAHs of similar hydrophobicity and
      molecular size, the field BSAFs were much lower and in the range 0.002 to 0.05.
      This PAH-PCB dichotomy is consistent with recently reported much stronger binding
      to diesel soot (a form of BC) for PAHs than for PCBs of equal hydrophobicities.
      Lower BSAFs for the near-equilibrated PAHs (phenanthrene and fluoranthene) in the
      urban sediments relative to the background sediments were consistent with the
      larger presence of BC in the urban sediments. This study provides the first
      linked BSAF-BC field data that supports a causal relationship between strong soot
      sorption and reduced bioavailability for PAHs.

PMID- 15559276
TI  - Digestive bioavailability to a deposit feeder (Arenicola marina) of polycyclic
      aromatic hydrocarbons associated with anthropogenic particles.
AB  - Marine sediments around urban areas serve as catch basins for anthropogenic
      particles containing polycyclic aromatic hydrocarbons (PAHs). Using incubations
      with gut fluids extracted from a deposit-feeding polychaete (Arenicola marina),
      we determined the digestive bioavailability of PAHs from fly ashes, coal dusts,
      diesel soots, tire tread materials, and urban particulates. We found that gut
      fluids solubilize significant concentrations of PAHs from two tire treads, two
      diesel soots, and the urban particulates. However, PAHs in fly ashes and coal
      dusts were not available to the digestive agents in gut fluid. Potential
      digestive exposure to PAHs is much greater than that predicted to be available
      from these materials using equilibrium partitioning theory (EqP). Amending an
      already-contaminated sediment with fly ash decreased phenanthrene solubilization
      by gut fluid. In contrast, addition of tire tread to the sediment resulted in
      increased solubilization of four PAHs by gut fluid. Therefore, addition of
      certain types of anthropogenic particles to sediments may result in an increase
      in bioavailable PAHs rather than a net decrease, as predicted by EqP. Difficulty
      in predicting the amount of change due to amendment may be due to interactions
      occurring among the mixture of compounds solubilized by gut fluid.

PMID- 15559277
TI  - Degradation of metolachlor in bare and vegetated soils and in simulated water
      sediment systems.
AB  - A study was conducted to determine the half-life (t1/2), degradation rate, and
      metabolites of metolachlor in a water-sediment system and in soil with and
      without switchgrass. Metolachlor degradation in a laboratory was determined in
      sediment from Bojac sandy loam soil incubated at 24 degrees C. The study also was
      conducted in a greenhouse on tilted beds filled with Bojac soil and planted with
      switchgrass. In both experiments, samples were collected at days 0, 7, 14, 28,
      42, 56, and 112 and analyzed for metolachlor and its major metabolites. The water
      sediment oxidation-reduction potential took 28 d to reach -371 mV and the pH
      increased from 5.6 to 6.5 by the last sampling day (day 112). The average soil
      temperature of the tilted beds with or without switchgrass during the study was
      21degrees C and the soil moisture content was 23% by volume. The t1/2 of
      metolachlor was 34 d in sediment and 8 d in the water phase. The t1/2 of
      metolachlor in soil from the switchgrass filter strip (6 d) was not different
      from that in soil without grass (9.6 d). The metolachlor metabolites
      ethanesulfonic acid (ESA) and oxanilic acid (OA) were detected in the water
      sediment system and in soil from tilted beds. In both sediment and soil from
      tilted beds, the two metabolites peaked by day 56 of incubation and declined
      after that, indicating transformation to other products. In the water-sediment
      system, greater quantities of OA and ESA were detected in sediment than in the
      aqueous phase. The production of OA and ESA in the watersediment system occurred
      in the first 28 d, when the system was at an aerobic redox state. Metolachlor can
      degrade in sediment and the relatively high soil temperature and moisture level
      accelerated its breakdown in beds with and without switchgrass. Under warm and
      moist soil conditions, the presence of switchgrass has no effect on the
      degradation of metolachlor.

PMID- 15559278
TI  - Soil properties affecting toxicity of zinc to soil microbial properties in
      laboratory-spiked and field-contaminated soils.
AB  - The effects of soil properties and zinc (Zn) availability on the toxicity of Zn
      to soil microbial processes are poorly understood. Three soil microbial processes
      -potential nitrification rate (PNR), substrate (glucose)-induced respiration
      (SIR), and a maize residue respiration (MRR)--were measured in 15 European
      topsoils (pH 3.0-7.5; total Zn 7-191 mg/kg) that were freshly spiked with ZnCl2.
      The Zn toxicity thresholds of 20 to 50% effective concentrations (EC20s and
      EC50s) based on total concentrations of Zn in soil varied between 5- and 26-fold
      among soils, depending on the assay. The Zn toxicity thresholds based on Zn
      concentrations in soil solution varied at least 10-fold more than corresponding
      total metal thresholds. Soil pH had no significant effect on soil total Zn
      toxicity thresholds, whereas significant positive correlations were found between
      these thresholds and background Zn for the PNR and SIR test (r = 0.74 and 0.71,
      respectively; log-log correlations). No such trend was found for the MRR test.
      Soil solution-based thresholds showed highly significant negative correlations
      with soil pH for all assays that might be explained by competition of H+ for
      binding sites, as demonstrated for aquatic species. The microbial assays were
      also applied to soils collected under galvanized pylons (three sites) where
      concentrations of total Zn were up to 2,100 to 3,700 mg Zn/kg. Correlations
      between concentrations of total Zn and microbial responses were insignificant at
      all sites even though spiking reference samples to equivalent concentrations
      reduced microbial activities up to more than 10-fold. Differences in response
      between spiked and field soils are partly but not completely attributed to the
      large differences in concentrations of Zn in soil solution. We conclude that soil
      pH has no significant effect on Zn toxicity to soil microbial processes in
      laboratory-spiked soils, and we suggest that community tolerance takes place at
      both background and elevated Zn concentrations in soil.

PMID- 15559279
TI  - Reduced grazing rates in Daphnia pulex caused by contaminants: implications for
      trophic cascades.
AB  - Ecotoxicological endpoints based on behavioral traits (e.g., predator avoidance,
      feeding, and locomotion) may be more sensitive and give more insights into
      patterns of sublethal toxicity than survivorship tests. In this study, the
      density-dependent grazing rate of Daphnia pulex pre-exposed to p,p'
      dichlorodiphenyldichloroethylene (DDE) (insecticide metabolite) and glyphosate
      (herbicide), via water or a vector, Scenedesmus spp., was assayed in laboratory
      experiments. The phytoplankton biomass was estimated from the chlorophyll
      content, and the pesticide uptake and turnover pattern in Daphnia and Scenedesmus
      were determined from parallel experiments with a radiolabeled source. Scenedesmus
      spp. relative net growth rate was inversely and linearly related to the density
      of the grazer. Daphnia pulex exhibited significant reductions in grazing rate:
      30% for those pre-exposed to p,p'-DDE via water and 40% for D. pulex pre-exposed
      to glyphosate via Scenedesmus spp. Through the process of trophic cascading, this
      impaired grazing allowed Scenedesmus spp. to grow at higher rates, 70 and 60%,
      respectively. The reduced grazing efficiencies were associated with the
      treatments that gave the highest body burden of p,p'-DDE (70 microg/g dry wt) and
      the lowest of glyphosate (13 mg/g dry wt). The pattern of results suggests a
      toxic effect of p,p'-DDE on D. pulex and a growth enhancement of Scenedesmus spp.
      in response to nitrogen and phosphorus in glyphosate excreted by D. pulex.

PMID- 15559280
TI  - Persistence of selected organophosphate and carbamate insecticides in waters from
      a coastal watershed.
AB  - Organophosphate and carbamate compounds are among the most widely used
      pesticides. Contamination of surface water by these compounds is of concern
      because of potential toxicity to aquatic organisms, especially those at lower
      trophic levels. In this study we evaluated the persistence of diazinon,
      chlorpyrifos, malathion, and carbaryl in waters from various sites in the Newport
      Bay-San Diego Creek watershed in southern California (USA). The persistence of
      diazinon and chlorpyrifos was much longer than that of malathion or carbaryl and
      was further prolonged in seawater. Microbial degradation contributed
      significantly to the dissipation of diazinon and chlorpyrifos in freshwater, but
      was inhibited in seawater, leading to increased persistence. In contrast,
      degradation of malathion and carbaryl was rapid and primarily abiotic. A greater
      temperature dependence was observed for carbaryl degradation in all waters and
      for diazinon degradation in freshwater. The interactions of pesticide persistence
      with water location, temperature, and type of pesticides suggest that site- and
      compound-specific information is needed when evaluating the overall
      ecotoxicological risks of pesticide pollution in a watershed. Because the
      persistence of diazinon and chlorpyrifos may increase significantly in seawater,
      mitigation should occur before the pesticides reach seawater. The relatively
      short persistence of these compounds in freshwater suggests that practices aimed
      at extending residence time (e.g., diversion to wetlands) may effectively reduce
      pesticide output to downstream water bodies.

PMID- 15559281
TI  - Polycyclic aromatic hydrocarbons in a highly industrialized urban estuary:
      inventories and trends.
AB  - The abundance and composition of polycyclic aromatic hydrocarbons (PAHs) in
      sediments of the main stem and southern branch of the Elizabeth River (VA, USA),
      a highly industrialized urban estuary in the Chesapeake Bay (USA) watershed, were
      examined relative to historical and toxic effects levels. Total PAH
      concentrations in Elizabeth River sediments exceeded those observed in Baltimore
      Harbor and the Anacostia River, two other regions of concern in the Chesapeake
      Bay. The sigmaPAH concentrations from samples collected in the vicinity of two
      former wood-treatment facilities in the Elizabeth River had the highest sigmaPAH
      when compared to coastal and estuarine systems around the world. Using a
      linearized diffusion model equation, as much as 69% of the variability in channel
      sediment sigmaPAH distribution could be ascribed to inputs associated with former
      wood-treatment facilities along the southern branch of the Elizabeth River.
      Comparison of PAH levels measured in channel samples to data collected during the
      early 1980s demonstrated a general trend toward reduction in contaminant
      concentrations for most regions of the Elizabeth River channel; however, steady
      state and increased sediment PAH concentrations in the vicinity of the former
      wood-treatment facilities were observed. Based on examination of the contaminant
      levels in Elizabeth River sediments using established sediment-quality criteria,
      the southern branch of the river remains a clear hazard to benthic and pelagic
      organisms.

PMID- 15559282
TI  - Pollution-induced community tolerance of soil microbes in response to a zinc
      gradient.
AB  - The long-term accumulation of Zn in soils provides the microbial community time
      to adapt to this heavy metal. To assess the effects of long-term exposure to Zn
      on the metabolic diversity and tolerance to Zn of soil microbial community, the
      pollution-induced community tolerance (PICT) method, based on the Biolog
      microtitre plate system, was used. It especially is useful to study gradients of
      pollutants for detecting PICT. Such a Zn gradient was found by selecting soils at
      increasing distances from galvanized electricity pylons at two sites where Zn
      accumulation had occurred over a period of decades. Soil metabolic profiles
      showed a humpbacked response to increasing soil Zn concentrations, indicating
      that accumulation of Zn up to 2,000 mg/kg did not decrease the metabolic
      biodiversity in the culturable fraction of the microbial community. This fraction
      of the microbial community showed significant PICT, because the effective
      concentration that reduces the metabolic biodiversity by 50% (EC50), values for
      Zn added to the Biolog wells increased by up to two orders of magnitude with
      increasing soil-Zn concentration along the transects. Significant PICT was
      detectable at soil Zn concentrations above approximately 300 mg/kg. The EC50
      values correlated more closely with soil total Zn than with soil pore water Zn.
      The results suggest that, although long-term exposure to Zn imposes stress on
      soil microbes, resulting in an increased tolerance, detectable PICT does not
      necessarily lead to a decrease in metabolic diversity.

PMID- 15559283
TI  - Highly persistent butyltins in northern marine sediments: a long-term threat for
      the Saguenay Fjord (Canada).
AB  - An exhaustive study of the distribution of butyltin species was conducted in the
      sediment of the Saguenay Fjord (Canada), a semi-enclosed marine system with
      sediment permanently submitted to sub-Arctic cold conditions. Concentrations of
      total butyltins (tributyltin [TBT], dibutyltin, and monobutyltin) ranged from 6
      to 288 ng Sn/g dry weight and were typical of those reported for contaminated
      coastal areas despite limited seasonal traffic of commercial vessels in the
      fjord. The distribution profiles of butyltin species in four sediment cores
      clearly indicated the high persistence of TBT that was dominating other species.
      The particular oceanographic conditions of the Saguenay Fjord (low seawater
      temperature, anoxic sediments, and low exchange rate of deep waters) combined
      with a high sediment/pore-water partition coefficient (Kdobs = 1.0 x 10(4) to 1.2
      x 10(4) L/kg) and a low sediment/ water diffusive flux of TBT (J1 = 13 x 10(-8)
      mol/m2/year) are responsible for the burial and preservation of TBT in this
      marine ecosystem. The half-life of TBT in deep sediment was estimated to be
      approximately 87+/-17 years (+/-SEM), which implies a much slower degradation
      rate than any previously reported. Finally, a flood event that occurred five
      years before the sampling enabled us to calculate a very slow diffusive flux from
      the preflood to the postflood layer (J2 = 2 x 10(-8) mol/m2/year), indicating an
      almost permanent sequestration of TBT in the buried layers.

PMID- 15559284
TI  - Influence of leaching medium and drying time between successive leaching periods
      on the emission of chromium, copper, and boron from treated wood.
AB  - Laboratory studies were conducted to determine leaching of Cu, Cr, and B from
      pine sapwood treated with Cr-Cu-B (CCB) preservative in different leaching media
      (ultrapure water [UPW], rainwater [RW], and soil water [SW]). Losses of metals
      from CCB-treated wood, expressed in percentage of initial content, were always
      highest for B (11.2-63.5%) and lowest for Cr (0.02-0.36%) in any of the leaching
      media assayed. Losses of B and Cr from treated wood were not affected by the
      leaching medium; however, losses of Cu were 1.5 to 2.5 times higher in SW than in
      UPW and RW. The influence of drying time between successive leaching periods on
      release of metals also was determined. Treated wood was submitted to wetting
      drying cycles of 24 h/d, 18 h/d, and 6 h/d in contact with the leaching medium
      over a total contact time of 276 h. For an equivalent contact period of CCB
      treated wood with either UPW or RW, leaching of B was from 1.1 to 1.9 times
      higher for continual wetting than under intermittent wetting conditions. Leaching
      of Cu was not affected by the wetting-drying periods when wood was in contact
      with RW, but it was 1.2 to 1.5 times higher for continual wetting with UPW. In
      general, leaching of Cr was not affected by the wetting-drying cycles when in
      contact with UPW or RW. However, when CCB-treated wood was in contact with SW
      under discontinuous wetting of 6 h/d, Cu and Cr emissions were approximately 1.2
      and 2.5 times higher, respectively, than with continuous wetting. This study
      shows that the type of leaching medium and the drying time between successive
      wetting periods must be considered when evaluating metal losses from CCB-treated
      wood during service life.

PMID- 15559285
TI  - Dietary assimilation and elimination of Cd, Se, and Zn by Daphnia magna at
      different metal concentrations.
AB  - This study examines the influences of Cd, Se, and Zn concentrations in ambient
      water on the assimilation, elimination, and release budget of metals, and the
      clearance rate of Daphnia magna through ingestion of phytoplankton diets. With
      increasing ambient metal concentration over two to three orders of magnitude, the
      assimilation efficiencies (AEs) of Cd and Se from two green algal species,
      Scenedesmus obliquus and Chlamydomonas reinhardtii, decreased significantly. In
      contrast, the Zn AE from ingested food, which typically was low (<7%), was not
      impacted by the difference in Zn or Cd concentrations in ingested cells. The Cd
      AE also was reduced significantly by a high Zn concentration in ingested algae,
      perhaps due to the competitive assimilation between the two metals. Metal
      elimination was determined after the daphnids were exposed to the radiolabeled
      diets for 3 d. The elimination rate constant was not dependent on the metal
      concentration in ingested food. Similarly, the routes of metal elimination
      (excretion, egestion, molting, and neonate production) were less influenced by
      the metal concentration. The rapid elimination of Se and Zn may be attributed to
      the transfer of these metals from mother to offspring. Except at the highest Cd
      (917 nM) and Se (1,333 nM) concentrations, there was no significant effect of
      metal concentration on the clearance rate of the animals. Consequently, the metal
      assimilation in D. magna may play an important role in the regulation of Cd and
      Se influx into the animals, whereas the regulation of the metal tissue burden in
      the animals is unlikely to be achieved through the metal elimination. The trophic
      transfer factors (TTF) of Cd and Se were related inversely to the metal
      concentration in the water, whereas the TTF of Zn was less variable at different
      Zn concentrations. The change of TTF with metal concentration will have important
      implication for ecotoxicity testing using D. magna, especially when the dietary
      exposure is incorporated.

PMID- 15559286
TI  - Development of toxicity identification evaluation procedures for pyrethroid
      detection using esterase activity.
AB  - Recent agrochemical usage patterns suggest that the use of organophosphate (OP)
      pesticides will decrease, resulting in a concomitant increase in pyrethroid
      usage. Pyrethroids are known for their potential toxicity to aquatic
      invertebrates and many fish species. Current toxicity identification evaluation
      (TIE) techniques are able to detect OPs, but have not been optimized for
      pyrethroids. Organophosphate identification methods depend upon the use of
      piperonyl butoxide (PBO) to identify OP-induced toxicity. However, the use of PBO
      in TIE assays will be confounded by the co-occurrence of OPs and pyrethroids in
      receiving waters. It is necessary, therefore, to develop new TIE procedures for
      pyrethroids. This study evaluated the use of a pyrethroid-specific antibody, PBO,
      and carboxylesterase activity to identify pyrethroid toxicity in aquatic toxicity
      testing with Ceriodaphnia dubia. The antibody caused significant mortality to the
      C. dubia. Piperonyl butoxide synergized pyrethroid-associated toxicity, but this
      effect may be difficult to interpret in the presence of OPs and pyrethroids.
      Carboxylesterase activity removed pyrethroid-associated toxicity in a dose
      dependent manner and did not compromise OP toxicity, suggesting that
      carboxylesterase treatment will not interfere with TIE OP detection methods.
      These results indicate that the addition of carboxylesterase to TIE procedures
      can be used to detect pyrethroids in aquatic samples.

PMID- 15559287
TI  - Using artificial streams to assess the effects of metal-mining effluent on the
      life cycle of the freshwater midge (Chironomus tentans) in situ.
AB  - In 2002, we developed an in situ life-cycle bioassay with Chironomus tentans in
      artificial streams to evaluate the effects of a complex metal mine effluent under
      ambient environmental conditions. The bioassay was tested in the field using
      effluent from the Copper Cliff Waste Water Treatment Plant at INCO (Sudbury, ON,
      Canada). Chironomus tentans were exposed throughout the life cycle to 45% Copper
      Cliff effluent, which is the average effluent concentration measured in Junction
      Creek (ON, Canada), the natural receiving environment. Chironomus tentans in the
      effluent treatment exhibited reduced survival (p = 0.001), reduced total
      emergence (p = 0.001), increased time-to-emergence (p = 0.001), and reduced
      hatching success (p = 0.001) relative to animals in the reference water
      treatment. Chironomus tentans in the effluent treatment were not significantly
      different from the reference in terms of growth, sex ratio, number of egg
      cases/female, and number of eggs/egg case. This research showed how a life-cycle
      bioassay could be used in situ to assess metal mine effluent effects on a benthic
      invertebrate.

PMID- 15559288
TI  - Toxicity of storm-water runoff after dormant spray application in a french prune
      orchard, Glenn County, California, USA: temporal patterns and the effect of
      ground covers.
AB  - Organophosphorous (OP) insecticides, especially diazinon, have been detected
      routinely in surface waters of the Sacramento and San Joaquin River watersheds,
      coincident with rainfall events following their application to dormant orchards
      during the winter months. Preventive best management practices (BMP) aim at
      reducing off-site movement of pesticides into surface waters. Two proposed BMPs
      are: The use of more hydrophobic pyrethroid insecticides believed to adsorb
      strongly to organic matter and soil and the use of various types of ground cover
      vegetation to increase the soil's capacity for water infiltration. To measure the
      effectiveness of these BMPs, storm water runoff was collected in a California
      prune orchard (Glenn County, CA, USA) during several rainstorms in the winter of
      2001, after the organophosphate diazinon and the pyrethroid esfenvalerate were
      applied to different orchard sections. We tested and compared acute toxicity of
      orchard runoff from diazinon- and esfenvalerate-sprayed sections to two species
      of fish (Pimephales promelas, Onchorhynchus mykiss) and three aquatic
      invertebrates (Ceriodaphnia dubia, Simocephalus vetelus, Chironomus riparius),
      and determined the mitigating effect of three ground cover crops on toxicity and
      insecticide loading in diazinon-sprayed orchard rows. Runoff from the
      esfenvalerate-sprayed orchard section was less toxic to waterflea than runoff
      from the diazinon-sprayed section. However, runoff from the orchard section
      sprayed with esfenvalerate was highly toxic to fish larvae. Samples collected
      from both sections one month later were not toxic to fish, but remained highly
      toxic to invertebrates. The ground cover crops reduced total pesticide loading in
      runoff by approximately 50%. No differences were found between the types of
      vegetation used as ground covers.

PMID- 15559289
TI  - Osmotic distress: a probable cause of fish kills on exposure to a subbloom
      concentration of the toxic alga Chattonella marina.
AB  - Mortality, changes in blood osmolality, and pO2 in the goldlined seabream
      (Rhabdosargus sarba) on exposure to a subbloom concentration (2,000 cells/ml) of
      a toxic red tide alga, Chattonella marina, were investigated and related to
      quantitative ultrastructural alterations of the gill. The median lethal time
      (LT50) was 6 h. Significant induction of filamental chloride cells (CCs)
      (increases in CC density, apical opening area, fractional area, volume densities
      of CCs, and mitochondria within CCs), concomitant with a significant reduction in
      blood osmolality, was found within 3 h of exposure to C. marina. Further
      reduction in blood osmolality (67%) and a drastic decline of pO2 (70%) were
      detected in moribund fish after 6 h. Fish were also subjected to severe salinity
      stress (abrupt transfer to 0 and 60% salinities), and the same parameters were
      measured. Our quantitative ultrastructural and physiological data suggest that
      fish exposed for 6 h to C. marina (2,000 cells/ml) suffered similar but more
      severe osmotic distress as compared to that induced by abrupt transfer to 60%
      hypersaline water. Results of the salinity stress experiment also showed that
      suffocation was not a secondary response induced by osmotic impairment in the
      moribund fish. Osmoregulatory failure in conjunction with suffocation may be the
      cause of death following exposure to C. marina. The findings of this study
      provide evidence that C. marina, even in concentrations below visible blooms, can
      pose a significant threat to marine fish.

PMID- 15559290
TI  - Barramundi as an indicator species for environmental monitoring in North
      Queensland, Australia: laboratory versus field studies.
AB  - The dose-response relationship for hepatic 7-ethoxyresorufin-O-deethylase (EROD)
      induction in barramundi (Lates calcarifer) was examined under controlled
      laboratory conditions for 15 d using farm-reared barramundi. These results were
      compared with EROD activity measured in barramundi collected from two rivers
      catchments (impacted and nonimpacted) in northern Queensland, Australia.
      Barramundi were dosed by intraperitoneal injection with a known cytochrome P4501A
      (CYP1A) inducer, beta-naphthoflavone (beta-NF), at 5, 10, and 50 mg kg(-1) using
      two controls: A vehicle control (corn-oil injected) and an experimental control
      (no injection). The EROD induction occurred within 4 h in the 5, 10, and 50 mg
      beta-NF kg(-1) exposures, reaching mean maximum activities of 88.6 (+/-51.9),
      85.5 (+/-91.7), and 149.1 (+/-106.4) pmol min(-1) mg protein(-1), respectively.
      Mean EROD activities remained low in the corn-oil controls (2.1+/-1.8 pmol min(
      1) mg protein(-1)) and experimental controls (5.3+/-4.4 pmol min(-1) mg protein(
      1)) throughout the study. Barramundi demonstrated a rapid response curve, which
      was dose dependent (50 > 10 > 5 mg beta-NF kg(-1)) and decreased progressively
      over time from induction. Measurement of total cytochrome P450 content (nmol mg
      protein(-1)) was not dose dependent. The EROD activities from field-collected
      barramundi from the Johnstone River (impacted) and Olive River (nonimpacted)
      suggest exposure to low-level contaminants in the Johnstone River fish only. With
      more controlled laboratory and field studies, barramundi have the potential to
      become a major indicator species in assessing exposure to environmental
      contaminants in coastal areas throughout northern Queensland, Australia.

PMID- 15559291
TI  - Partial life-cycle toxicity and bioconcentration modeling of
      perfluorooctanesulfonate in the northern leopard frog (Rana pipiens).
AB  - A number of recent monitoring studies have demonstrated elevated concentrations
      of perfluorooctanesulfonate (PFOS) in humans and wildlife throughout the world.
      Although no longer manufactured in the United States, the global distribution and
      relative persistence of PFOS indicates a need to understand its potential
      ecological effects. Presently, little is known concerning toxicity of PFOS in
      chronic exposures with aquatic species. Therefore, we evaluated the effects of
      PFOS on survival and development of the northern leopard frog (Rana pipiens) from
      early embryogenesis through complete metamorphosis. Exposures were conducted via
      water at measured PFOS concentrations ranging from 0.03 to 10 mg/L. Animals
      exposed to 10 mg/L began dying within approximately two weeks of test initiation.
      Survival was not affected by PFOS at lower concentrations; however, time to
      metamorphosis was delayed and growth reduced in the 3-mg/L treatment group.
      Tadpoles readily accumulated PFOS directly from water. Using a one-compartment
      bioaccumulation model, growth was shown to have a modest impact on steady-state
      PFOS concentrations. Variability in observed growth rates and the possible
      contribution of a size-dependent decrease in PFOS elimination rate contributed
      uncertainty to modeling efforts. Nevertheless, fitted uptake and elimination rate
      constants were comparable to those determined in earlier studies with juvenile
      rainbow trout. Overall, our studies suggest that R. pipiens is not exceptionally
      sensitive to PFOS in terms of either direct toxicity or bioconcentration
      potential of the chemical.

PMID- 15559292
TI  - Plant uptake and translocation of highly weathered, soil-bound technical
      chlordane residues: data from field and rhizotron studies.
AB  - It has been observed that plants are susceptible to uptake from soil and in
      planta transport of technical chlordane, in spite of its hydrophobicity and
      sequestration within the soil matrix due to weathering. Field and rhizotron
      studies were conducted with Cucurbitaceae planted in highly weathered, chlordane
      contaminated soil to investigate details of soil-to-plant contaminant uptake. In
      the field-work, Cucurbita pepo L. (zucchini) was grown in soil at four levels of
      chlordane contamination: Clean (<limits of quantitation, 5 ng/g), low (average,
      370 ng/g), medium (average, 1,951 ng/g), and high (average, 4,572 ng/g). The
      analysis of plant tissues (root, stem, leaf, and fruit) resulted in the detection
      of chlordane consistently at the highest concentration in the root tissue at each
      level of soil contamination. As the soil chlordane concentration increased, the
      average chlordane concentration in the root tissue increased as follows: Clean,
      370 ng/g; low, 8,130 ng/g; medium, 21,800 ng/g; high, 29,400 ng/g. Further
      analysis of the field-grown plants showed distinct differences in both the
      proportional distribution of chlordane among the plant tissues and the pattern of
      the chlordane residues in each tissue type. These differences are attributed to
      plant uptake from soil versus uptake from air. In the rhizotron studies, uptake
      of chlordane residues by C. pepo L. was compared with that of another
      Cucurbitaceae, Cucumis sativus L. (cucumber). Xylem sap from the rhizotron-grown
      plants was collected and analyzed for chlordane, in addition to determination of
      chlordane residues in soil, roots, and aerial plant tissue. Component fractions
      and enantiomer fractions of both chiral and achiral chlordanes were followed
      through soil, root, xylem sap, and aerial tissue compartments. They indicate that
      the xenobiotic residues translocate enantioselectively from the soil matrix into
      and through the plant environment with genera-specific patterns. The
      determination of chlordanes at ng/g concentration explicitly for the first time
      in the xylem sap of plants grown in contaminated soil confirms the presence of a
      soil-sequestered and highly hydrophobic organic contaminant within the aqueous
      plant environment.

PMID- 15559293
TI  - Feminization of female leukophore-free strain of Japanese medaka (Oryzias
      latipes) exposed to 17beta-estradiol.
AB  - The recently developed female leukophore-free (FLFII) strain of Japanese medaka
      (Oryzias latipes) carries DNA markers for the identification of genotypic sex.
      Information regarding genotypic sex is useful for tests in which endocrine
      disrupting compounds may masculinize or feminize fish. In the present study,
      methods were developed to automate DNA extraction and profiling for rapid
      determination of genotypic sex. Adequate amounts of DNA were isolated by robotic
      extraction procedures from the caudal fin. New primers were developed to include
      an 18-base pair segment that is in the X chromosome of female medaka but is
      absent in the Y chromosome of male medaka. Automated profiling methods with 96
      well plates permitted analysis of the genomic sex of medaka at rates of up to 500
      fish/d. We investigated the sensitivity of the FLFII strain to the feminizing
      effects of the potent estrogen 17beta-estradiol (E2), and we compared this
      sensitivity to that of a wild strain that has been used widely in the study of
      endocrine-disrupting compounds. All FLFII medaka exposed to 1 microg/L of E2 (n =
      50) had the female gonadal phenotype (i.e., ovaries), and all but one wild-strain
      medaka exposed to 1 microg/L of E2 (i.e., 47 of 48 fish) had the female gonadal
      phenotype, indicating that the FLFII and wild strains have approximately equal
      sensitivities to the feminizing effects of E2. Analysis of the genotype of FLFII
      medaka confirmed that 100% of fish with the male genotype had been feminized to
      the female gonadal phenotype. The FLFII strain is an excellent teleost model for
      detecting feminization or masculinization of fish, and automated methods can be
      used for rapid analysis of the genotypic sex of FLFII medaka.

PMID- 15559294
TI  - Location-specific ecotoxicological risk assessment of metal-polluted soils.
AB  - When chemical analysis indicates metal pollution, a second-tier method is needed
      to evaluate whether toxic effects occur at the polluted sites. A method based on
      pollution-induced community tolerance (PICT) was developed using samples taken
      from locations polluted with sewage more than 20 years ago. Microorganisms
      extracted from soil samples were exposed to a concentration range of zinc,
      nickel, copper, chromium (III), or chromium (VI) salts in a buffer suspension.
      The remaining activity of the intoxicated microorganisms was determined by color
      formation with 31 different organic substrates in microtiter plates.
      Microorganisms from moderately Zn-polluted sites (>45 mg/kg) showed an increased
      tolerance for zinc. Nickel tolerance was observed at 51 mg Ni/kg soil, chromium
      (VI) tolerance at 923 mg Cr/kg. In most cases, tolerance also was observed at
      higher concentrations. High concentrations of 1,494 mg Cu/kg or 3,935 mg Cr/kg
      did not show PICT, indicating a limited bioavailability of Cu and Cr at these
      sites. The benefits of our method are its greater sensitivity compared to other
      tests used at these sites, and its specificity for those metals that exceed
      allowable levels.

PMID- 15559295
TI  - Unwarranted variations in the quality of health care: can the law help medicine
      provide a remedy/remedies?
AB  - This Article reviews the essential findings of studies of variations in quality
      of care according to three categories of care: effective care, preference
      sensitive care, and supply-sensitive care. It argues that malpractice liability
      and informed consent laws should be based on standards of practice that are
      appropriate to each category of care. In the case of effective care, the legal
      standard should be that virtually all of those in need should receive the
      treatment, whether or not it is currently customary to provide it. In the case of
      preference-sensitive care, the law should recognize the failure of the doctrine
      of informed consent to assure that patient preferences are respected in choice of
      treatment; we suggest that the law adopt a standard of informed patient choice in
      which patients are invited, not merely to consent to a recommended treatment, but
      to choose the treatment that best advances their preferences. In the case of
      supply-sensitive care, we suggest that physicians who seek to adopt more
      conservative patterns of practice be protected under the "respectable minority"
      or "two schools of thought" doctrine.

PMID- 15559296
TI  - [Blood rheology and physiological functions. 3. Blood microcirculation and oxygen
      transport].

PMID- 15559297
TI  - [Long-term outcomes and complications associated with the use of a Groningen
      voice prosthesis].
AB  - We have been using the Groningen voice prosthesis as a method of voice
      restoration after total laryngectomy for approximately five years. During this
      period, the Groningen voice prosthesis has been used in 19 patients and a total
      of 125 unit replacements have been performed. No serious complications have
      occurred to date. Upon examination of the voice restoration results, exchange
      frequency, and complications, we noted that 15 out of 19 patients (78.9%) were
      able to maintain a good voice quality, including cases with long-term observation
      periods. Voice restoration was difficult in the remaining 4 cases. The overall
      mean exchange period was 4.5 months, with 2.5 months being the shortest exchange
      interval in cases without complications. The mean exchange period for cases
      without complications was 6.1 months. No serious complications, such as a foreign
      body in the trachea, were encountered. However, several problems with water
      leakage occurred and were managed appropriately. Aspiration pneumonia from
      repeated water leakage did not occur, and no cases of TE shunt closure were
      encountered. These problems may occur with further aging. Thorough follow-ups
      will be continued in the future.

PMID- 15559298
TI  - [Rapid prototyping of the larynx for laryngeal frame work surgery].
AB  - A detailed understanding of the three-dimensional (3D) structure of the larynx is
      important for determining appropriate methods and approaches for laryngeal frame
      work surgery. In this study, a 3D laryngeal model was constructed based on
      postoperative helical CT data obtained after lateral cricoarytenoid muscle (LCA)
      pull surgery (Iwamura) for the treatment of unilateral vocal fold paralysis. The
      anatomical configurations of the arytenoid cartilages and the optimal approaches
      for laryngeal frame work surgery were then examined. A 3D model of the human
      larynx was prototyped using a selective laser sintering method. A compound powder
      of plastic nylon and an inorganic substance (glass beads) was used as the raw
      material. The cricoid cartilage and the arytenoid cartilages were prototyped, and
      the configurations of the arytenoid cartilages were evaluated. The results were
      similar to those of previous reports. The arytenoid cartilage of the unaffected
      side moved downward while adducting, and the vocal process moved inwards and
      downwards. On the other hand, the paralyzed arytenoid cartilage moved neither
      inward nor downward, and the vocal process was fixed at an outer and upper
      position. Next, the thyroid cartilage was added to the model to determine the
      optimal location of the window in the thyroid cartilage for the LCA pull surgery.
      The window after the first surgery was largened using a surgical drill. The 3D
      prototype model was useful for understanding the complex configurations of the
      laryngeal anatomy, and to determine the optimal approaches for laryngeal frame
      work surgery, etc.

PMID- 15559299
TI  - [Clinical usefulness of odor stick identification test for patients with
      olfactory disturbance].
AB  - The odor stick identification test for Japanese (OSITJ) is the latest in
      measuring olfactory identification. It consists of 13 odorants familiar to the
      Japanese population. We studied the relationship between the Japanese standard
      olfactory test (T & T olfactometer) and the OSITJ in 182 patients with olfactory
      disturbance. The identification ratio in 2 of OSITJ tests using 13 odorants was
      correlated significantly negatively with the detection and recognition threshold
      measured by the T & T olfactometer. A high correlation between identification
      ratio and olfactory thresholds was maintained even when the number of odorants in
      the OSITJ was reduced to 2. For each odorant used, the identification ratio
      correlated significantly with olfactory thresholds. Results from the OSITJ
      provide a measure of the degree of olfactory deficit because the ratio of correct
      answers obtained by the OSITJ decreased gradually with of the severity of
      olfactory disturbance. Compared to the T & T olfactometer, the OSITJ has several
      advantages for use in the clinic. These include minimal odor pollution of the
      test room, simplicity of use, and shorter clinical time needed to administer the
      test. The OSITJ may be ideal for use in screening due to the minimum number of
      odorants needed. In conclusion, the OSITJ is useful for detecting and evaluating
      olfactory disturbance in Japanese people.

PMID- 15559300
TI  - [Case of NK/T-cell lymphoma of the larynx with hemophagocytic syndrome].
AB  - We report the case of a 67-year-old man with NK/T cell lymphoma of the larynx
      accompanied by hemophagocytic syndrome (HPS) who reported throat paresthesia and
      was referred for evaluation of a laryngeal tumor extending from the left false
      vocal cord to the arytenoids. Two separate biopsies from the larynx yielded a
      histological diagnosis of NK/T-cell lymphoma, nasal and nasal type. Since he
      showed pancytopenia and remittent fever soon after admission, bone marrow was
      examined and showed severe hemophagocytosis, leading to a diagnosis of HPS. He
      died of circulatory and respiratory distresses due to HPS about one month after
      admission. HPS develops with symptoms of fever, cytopenia, and liver dysfunction,
      and is characterized by systemic proliferation of benign hemophagocytic
      histiocytosis in the bone marrow, lymph nodes, liver, and spleen. To the best of
      our knowledge, this is only the second case of NK/T-cell lymphoma of the larynx
      with hemophagocytic syndrome to be reported in the Japanese literature.

PMID- 15559301
TI  - [Treatment of Alzheimer's disease].

PMID- 15559302
TI  - [Role of synaptotagmin and its related molecules in regulated secretion].

PMID- 15559303
TI  - [Silkworm mutants whose deficiency of epidermal urate granules causes translucent
      larval skin phenotypes].

PMID- 15559304
TI  - [Molecular clutch mechanisms regulating axon outgrowth].

PMID- 15559305
TI  - [Genome-wide SNP association study to identify genes related to myocardial
      infarction and their functional analyses].

PMID- 15559306
TI  - [Systematic analysis of protein interaction network using human full-length
      cDNA].

PMID- 15559307
TI  - [Analysing protein folding transition state using protein engineering].

PMID- 15559308
TI  - [Fugu genome: the smallest genome size in vertebrates].

PMID- 15559309
TI  - [Catalytic reactions in protein cavities: molecular design of metalloenzymes].

PMID- 15559310
TI  - [Multicenter study in ophthalmology--importance of epidemiological study].

PMID- 15559311
TI  - [Clinical course and macular retinal circulation of macular retinal epithelium
      atrophy].
AB  - PURPOSE: To investigate the clinical course of age-related maculopathy that
      mainly consists of retinal pigment epithelial abnormality and macular retinal
      circulation between the affected eye and the fellow normal eye. PATIENTS AND
      METHODS: Seventeen patients (19 eyes) with age-related maculopathy were followed
      for more than two years. We investigated visual acuity, ocular fundus appearance,
      and fundus angiographic findings. We studied macular retinal leukocyte blood flow
      measured by blue field simulation in 19 patients whose fellow eye was normal.
      RESULTS: Age-related maculopathy in 18 eyes (95%) showed no change and choroidal
      neovasculation did not occur during the observation period. Male patients (88%)
      were more affected than female patients (12%). The visual acuity in the 18 eyes
      (95%) did not change. Only one case lost two lines of visual acuity, and the area
      of macular degeneration increased. Macular retinal leukocyte circulation
      expressed by the leukocyte density, and leukocyte density multiplied by the
      leukocyte velocity in the affected eyes deteriorated compared to the normal
      fellow eyes. CONCLUSION: We demonstrated that progression of age-related
      maculopathy is very slow, and macular retinal leukocyte circulation measured by
      blue field simulation may be disturbed in age-related maculopathy.

PMID- 15559312
TI  - [Retinopathy of prematurity in extremely low birth weight infants: a Tokyo
      multicenter study].
AB  - OBJECTIVE: To investigate how the increase in survival rate in extremely low
      birth weight (a birth weight of 1,000 g or less) infants had affected the
      incidence of retinopathy of prematurity (ROP) and the frequency of laser
      treatment. METHODS: We retrospectively reviewed the medical records of 122
      surviving premature infants with birthweights less than 1,000 g to determine the
      severity of ROP observed at 16 neonatal intensive care units in Tokyo between
      April and October 2002. RESULTS: The survival rate was 85.6%. The mean
      gestational age was 26.74 weeks and the mean birth weight was 782.25 g. One
      hundred-and-five infants (86.1%) developed ROP, fifty (41.0%) received laser
      treatment, and six (4.9%) had retinal detachment. The median postmenstrual age
      (gestational age at birth plus chronological age in weeks, PMA) at the onset of
      ROP was 32.5 weeks, and the first laser treatment was performed at the median PMA
      of 35.7 weeks. CONCLUSIONS: In these extremely low birth weight infants, there
      was an increase in the survival rate and in the incidence of severe ROP that
      progressed to the stage that required treatment.

PMID- 15559313
TI  - [Seasonal allergic conjunctivitis in Hakodate].
AB  - PURPOSE: We investigated seasonal allergic conjunctivitis in Hakodate. MATERIALS
      AND METHODS: The clinical records of 293 patients with allergy-like symptoms who
      were seen at the Departments of Ophthalmology and Otolaryngology of Hakodate
      Municipal Hospital in 2001 and 2002 were examined for pollinosis, and evaluated.
      The general severity of conjunctivitis was graded as (+), (++), and (+++). The
      allergen was identified by AlaSTAT and nasal provocation test. RESULTS: In March,
      June, and September 2001, and in March, April, and June 2002, many patients were
      examined. In 2001, 134 patients (87.0%) had allergic conjunctivitis, and 126
      patients (90.6%) had it in 2002. The severity of allergic conjunctivitis in May,
      June, and September was significantly (p<0.05) more severe than in February,
      March, and April. The major antigen rates for Cryptomeria japonica, Gramineae,
      Artemisia, and Betula platyphyia var. japonica were 22, 21, 8, and 3%. The
      specific IgE positive rates for Cryptomeria japonica, Betula platyphyia var.
      japonica, Gramineae and Artemisia were higher in March and April, in May, in
      June, and in September. CONCLUSION: The allergens of conjunctivitis in Hakodate
      were not the same as in the Kansai. We should consider the dispersion of pollens
      area by area.

PMID- 15559314
TI  - [Case of anterior ischemic optic neuropathy accompanied by Churg-Strauss
      syndrome].
AB  - BACKGROUND: Churg-Strauss syndrome (CSS) is a vasculitis which includes the three
      signs of bronchial asthma, hypereosinophilia, and vasculitis syndrome. We report
      a case in whom anterior ischemic optic neuropathy (AION) accompanied CSS. Such a
      case has not been reported previously in Japan. CASE: A 66-year-old woman with a
      history of bronchial asthma and eosinophilic pneumonia was hospitalized for
      fever, unusual feelings in both plantae and in a finger of her left hand,
      disturbance of visual acuity and visual field in the right eye, and skin rashes;
      a diagnosis of CSS was made. At the time of the first ophthalmological
      examination, AION was observed. Steroid therapy was started, but the treatment
      was not effective, despite an improvement in choroidal circulation confirmed by
      fluorescein angiography and indocyanine green angiography. In the unaffected eye,
      soft exudates appeared when the steroid dose was lowered and disappeared when the
      steroid dose was raised. CONCLUSION: Anterior ischemic optic neuropathy
      accompanied with Churg-Strauss syndrome resisted medical treatment and the
      prognosis was poor.

PMID- 15559315
TI  - [Case of late onset and isolated lattice corneal dystrophy with Asn544Ser (N544S)
      mutation of transforming growth factor beta-induced (TGFBI, BIGH3) gene].
AB  - PURPOSE: To report a case of lattice corneal dystrophy (LCD) with Asn544Ser
      (N544S) mutation of the transforming growth factor beta-induced (TGFBI) gene.
      CASE: A 68-year-old male patient with late-onset, sporadic LCD without corneal
      erosion. Amyloid deposits showing dot and lattice lines were seen in the mid to
      deep stroma. After obtaining appropriate informed consent, genomic DNA was
      amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: A
      heterozygous single base pair transition (AAT --> AGT), resulting in substitution
      of serine for asparagine at codon 544 of the TGFBI gene, was detected.
      CONCLUSION: The case was classified as atypical type IV because of the late
      onset, lack of corneal erosion, and amyloid deposits in the mid to deep stroma.

PMID- 15559316
TI  - [A Review 20: Vitreo-retinal surgery].

PMID- 15559317
TI  - [Quorum sensing: the possibility of the new antibiotic target in bacterial
      infection].
AB  - Expression of many virulence factors in P. aeruginosa is regulated by a cell
      density dependent mechanism called quorum sensing. Quorum sensing allows P.
      aeruginosa to sense the density of the surrounding bacterial population and to
      coordinately regulate transcription of various virulence genes. Pseucomonas
      aeruginosa is a common pathogen infecting chronic respiratory infections, such as
      diffuse panbronchiolitis (DPB) patients. Although these patients are typically
      treated with multiple anti-pseudomonal antibiotics, the infection is rarely
      eradicated and often results in mortality. In the 1980s it was reported that long
      term therapy with low doses of erythromycin improved the clinical symptoms of DPB
      patients colonized with P. qeruginosa. Recently it has been demonstrated that sub
      MIC concentrations of macrolides strongly inhibite Pseudomonas quorum sensing
      system. These data suggested a novel mechanism of quorum sensing regulation of
      antibiotic sensitivity.

PMID- 15559318
TI  - [Regulatory T cells and inflammatory bowel diseases].
AB  - Crohn's disease and ulcerative colitis are two major forms of human inflammatory
      bowel diseases (IBD). Their etiology is unknown, but increasing evidence indicate
      that immune mechanisms play an important role. It is well known that immune
      responses in the intestine remain in a state of controlled inflammation,
      suggesting that not only active suppression by regulatory T (TR) cells plays an
      important role in the normal intestinal homeostasis, but also its dysregulation
      leads to the development of IBD. This article reviews the unique aspects of TR
      cells and discuss how these control the intestinal homeostasis.

PMID- 15559319
TI  - [Molecules involved in characteristics of naive/memory B cells].
AB  - Memory B cells, which carry immunoglobulin somatic hypermutations, generate
      immunoglobulins rapidly and vigorously in the secondary immune response. We
      recently highlighted studies confirming that CD27 surface antigen is a memory B
      cell marker. By using the memory B-cell marker, peripheral blood B cells were
      clearly distinguished into naive and memory B cells. The B cells are further
      separated to three populations by the expressions of CD27 and IgD: IgD+CD27-
      naive B cells (circulating B cell 1: cB1), IgD+CD27+ unclass-switched memory B
      cells (cB2, so-called IgM memory B cells) and IgD-CD27+ class-switched memory B
      cells (cB3, switched memory B cells). Here we show molecules which are involved
      in characteristics of naive/memory B cells and their functions. This functionally
      distinct B cell subset and molecules involved in the subset may represent an
      important mechanism by which quiescent human B cells can initiate and propagate
      rapid and vigorous immune memory responses, and regulate the synthesis of
      low/high affinity antibodies.

PMID- 15559320
TI  - [The relationship between the intracellular redox status of immune cells and
      progression of hepatitis C virus related chronic liver disease].
AB  - It has been suggested that oxidative stress participates in the pathogenesis of
      hepatitis C virus infection. It also has been made clear that redox status in T
      cell and macrophage relates to the activity of virus infectious disease such as
      HIV infection. With such background we evaluated the relationship between the
      intracellular redox status of T cell and macrophage and the activity of HCV
      positive chronic liver disease. Intracellular GSH and GSSG levels of T cell and
      macrophage were determined in twenty-five HCV positive asymptomatic carriers (C
      ASC), sixty-three chronic hepatitis patients (C-CH), ten HCV positive liver
      cirrhosis patients (C-LC) and twenty-nine healthy controls. The intracellular GSH
      levels of T cell (T-GSH) significantly decreased in both C-CH and C-LC compared
      with healthy controls. No significant differences in the T-GSH levels were found
      between healthy controls and C-ASC. T-GSH levels of C-CH and C-LC were
      significantly lower compared with C-ASC. The intracellular GSH levels of
      macrophage (CD14-GSH) of C-LC were significantly decreased compared with healthy
      controls. The CD14-GSH levels of C-CH and C-LC were significantly lower compared
      with C-ASC. There was no correlation between intracellular GSH, GSSG levels and
      the serum levels of iron-related markers, fibrogenesis markers and other clinical
      parameters. These results suggest that the intracellular redox status of T cell
      and macrophage relates to the progression of HCV related chronic liver disease.

PMID- 15559321
TI  - [Significance of serum oxidative stress related markers and genotype of GST gene
      in the pathogeneses of primary biliary cirrhosis].
AB  - The studies using an immunohistological technique revealed that overexpression of
      oxidative stress-related substance such as HNE was observed in the liver of
      primary biliary cirrhosis patients. These data suggested that oxidative stress
      participated in the pathogenesis of primary biliary cirrhosis. Therefore we
      analyzed serum oxdative stress marker (8-OHdG) and anti oxidative substances (Mn
      SOD and TRX) to evaluate their clinical significance. In addition we analyzed the
      genotype of anti oxidative substance GST that has been reported to relate
      susceptibility of autoimmune disease. Serum levels of 8-OHdG, Mn-SOD and TRX in
      PBC patients were significantly higher than those of healthy subjects (P<0.001).
      Though there was no relation between serum level of 8-OHdG and clinical data,
      positive correlation between serum level of Mn-SOD, TRX and serum level of ALP,
      IgM was observed. Positive correlation was also observed between serum level of
      Mn-SOD and TRX. Serum levels of Mn-SOD of patients who responded to UDCA therapy
      were significantly higher than those of patients who did not response to therapy
      (P<0.01). Although genotypic difference of GSTM1 and GSTT1 by peripheral blood
      mononuclear cells did not relate to susceptibility of PBC, serum titer of AMA of
      GSTM1 null and GSTT1 null patients were significantly higher than those of GSTM1
      positive and/or GSTT1 positive patients (P< 0.05). These findings suggest that
      serum oxidative stress-related markers may reflect the extent of liver damage of
      PBC, and may relate to the efficacy of UDCA therapy on PBC. It also made clear
      that genotype of GST related to the titer of AMA.

PMID- 15559322
TI  - [Clinical significance of cevimeline hydrochloride in the treatment of dry mouth
      in patients with Sjogren's syndrome].
AB  - To evaluate the efficacy and safety of cevimeline hydrochloride for the treatment
      of dry mouth in patients with Sjogren's syndrome (SS), eight SS patients received
      30 mg of cevimeline twice or three times daily for 24 weeks. Six out of the eight
      patients had improvement in dry mouth. Five patients had more than 20% increase
      in saliva secretion. In the assessment of salivary gland scintigraphy, three
      patients showed improvement. There was a significant negative correlation between
      the improvement of saliva secretion and the severity of tissue damage assessed by
      MR sialography (r= - 0.754, p<0.05). One patient stopped cevimeline at 4 weeks
      because of headache and nausea. There was no significant change in laboratory
      data. Cevimeline is safe and effective medicine for dry mouth in patients with
      SS, in particular, with less severe salivary gland destruction.

PMID- 15559323
TI  - [Successful treatment of intravenous cyclophosphamide pulse therapy for lupus
      myelitis with urinary disturbance and acute confusional state].
AB  - A 18-year-old female had low grade fever, butterfly rush, proteinuria,
      leukocytopenia and hypocomplimentemia in 1988, and she was diagnosed as systemic
      lupus erythematosus (SLE) with lupus nephritis (WHOIIb). Treatments with
      prednisolone and mizoribine resulted in the remission for three years. In May
      2001, she presented neurosis and polakisuria despite of the increase of
      prednisolone to 20 mg/day. Finally, she admitted in our hospital because of manic
      and repressive state and disorientaion. A brain MRI revealed high intensity
      lesions in bilateral basal ganglia in T2 weighted images, and cerebrospinal fluid
      showed elevated protein and IFN-alpha (421 IU/ml). In addition, she manifested
      neurogenic bladder, muscle weakness and hyperactive deep tendon reflex of
      bilateral lower limbs due to both supranuclear disorder and hypesthesia under the
      Th 10 level. Spinal MRI revealed marked atrophy and high intensity signals at the
      middle to lower thoracic spinal cord in T2 weighted images, indicating
      complication of lupus myelitis as well as cerebral involvement. Although the
      symptoms of CNS lupus did not respond to prednisolone, twelve monthly
      cyclophosphamide pulse therapy (IV-CY) has resolved urinary disturbance, muscle
      weakness and sensory loss, along with the improvement of both cerebral and spinal
      MRI images. Lupus myelitis and neurogenic bladder are the rare, but very
      refractory manifestation among CNS involvement of SLE. We here propose IV-CY as
      an invaluable choice for the treatment of not only active lupus myelitis but also
      neurogenic bladder resisted for steroid.

PMID- 15559324
TI  - [A case of mixed connective tissue disease successfully treated for
      hemophagocytic syndrome with intermittent intravenous injection of
      cyclophosphamide].
AB  - A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness
      of lower extremities in October 2001. In December, she felt difficulty in walking
      due to muscle weakness. In January 2002, she admitted another hospital because of
      dyspnea on exertion and edema of lower extremities. Laboratory test revealed
      leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP
      antibodies. Her chest computed tomography (CT) showed severe interstitial
      pneumonia. Cardiac echogram revealed that she had pericardial effusion and
      pulmonary hypertension. Then she was transferred to Keio University Hospital and
      she was diagnosed as having mixed connective tissue disease (MCTD) manifestating
      myositis, interstitial pneumonia, pulmonary hypertension and pericarditis.
      Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse
      therapy was begun and her symptoms were gradually improved. In middle of
      February, she complained of high fever over 39.0 degrees C. Bacterial culture
      tests were negative and laboratory data indicated pancytopenia and a high level
      of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone
      marrow specimens and she was diagnosed as having hemophagocytic syndrome
      associated with MCTD. mPSL pulse therapy was not effective and intermittent
      cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of
      the symptoms. This case suggested the effectiveness of IV-CY therapy in patients
      with corticosteroid-resistant HPS associated with connective tissue diseases.

PMID- 15559325
TI  - [A female case of hyper-IgM immunodeficiency syndrome with uncommon skin
      manifestations].
AB  - A 11-year-old female admitted to our hospital because of erythema of the face and
      the trunk, and a wide and dense cluster of verruca vulgaris on the right sole.
      She had no family history of immunodeficiency, no perinatal abnormality, no
      growth abnormality, or no history of severe infections. From the age of 4 years,
      she noticed erythema around her nose. At the age of 9 years, small erythema and
      papules appeared on her chest. In January, 2003, erythema around her nose and
      papules of the trunk spread rapidly, and she also felt fatigue and effort
      dyspnea. Laboratory examinations revealed near absence of serum IgG, and IgE,
      high serum IgM (525 mg/dl), and normal IgA and IgD. Thl/Th2 ratio was 36.9. We
      diagnosed her as having hyper-IgM syndrome. Histological examinations of a skin
      biopsy showed the infiltration composed of mainly histiocytes,and mildly atypical
      CD8 + T cells around the blood vessels in the dermis. We concluded her skin
      manifestations as reactive lymphohistiocytic infiltration at the base of
      immunodeficiency and durable stimulation of various antigens. Her skin
      manifestations improved transiently by the intravenous immunogrobulin and
      corticosteroids therapy.

PMID- 15559326
TI  - OSHA compliance issues. Overexposure to silver on a programmed lead inspection.

PMID- 15559327
TI  - Case studies: identification of potential sources of arsenic exposure during
      scrapyard work at a former uranium enrichment facility.

PMID- 15559328
TI  - Analytical techniques and method validation for the measurement of selected
      semivolatile and nonvolatile organofluorochemicals in air.
AB  - The widespread use of semi- and nonvolatile organofluorochemicals in industrial
      facilities, concern about their persistence, and relatively recent advancements
      in liquid chromatography/mass spectrometry (LC/MS) technology have led to the
      development of new analytical methods to assess potential worker exposure to
      airborne organofluorochemicals. Techniques were evaluated for the determination
      of 19 organofluorochemicals and for total fluorine in ambient air samples. Due to
      the potential biphasic nature of most of these fluorochemicals when airborne,
      Occupational Safety and Health Administration (OSHA) versatile sampler (OVS)
      tubes were used to simultaneously trap fluorochemical particulates and vapors
      from workplace air. Analytical methods were developed for OVS air samples to
      quantitatively analyze for total fluorine using oxygen bomb combustion/ion
      selective electrode and for 17 organofluorochemicals using LC/MS and gas
      chromatography/mass spectrometry (GC/MS). The experimental design for this
      validation was based on the National Institute of Occupational Safety and Health
      (NIOSH) Guidelines for Air Sampling and Analytical Method Development and
      Evaluation, with some revisions of the experimental design. The study design
      incorporated experiments to determine analytical recovery and stability, sampler
      capacity, the effect of some environmental parameters on recoveries, storage
      stability, limits of detection, precision, and accuracy. Fluorochemical mixtures
      were spiked onto each OVS tube over a range of 0.06-6 microg for each of 12
      compounds analyzed by LC/MS and 0.3-30 microg for 5 compounds analyzed by GC/MS.
      These ranges allowed reliable quantitation at 0.001-0.1 mg/m3 in general for
      LC/MS analytes and 0.005-0.5 mg/m3 for GC/MS analytes when 60 L of air are
      sampled. The organofluorochemical exposure guideline (EG) is currently 0.1 mg/m3
      for many analytes, with one exception being ammonium perfluorooctanoate (EG is
      0.01 mg/m3). Total fluorine results may be used to determine if the individual
      compounds quantified provide a suitable mass balance of total airborne
      organofluorochemicals based on known fluorine content. Improvements in precision
      and/or recovery as well as some additional testing would be needed to meet all
      NIOSH validation criteria. This study provided valuable information about the
      accuracy of this method for organofluorochemical exposure assessment.

PMID- 15559329
TI  - Isocyanate exposures in autobody shop work: the SPRAY study.
AB  - Isocyanates, known to cause respiratory sensitization and asthma, are widely used
      in automotive refinishing where exposures to aliphatic polyisocyanates occur by
      both inhalation and skin contact. The work reported here, the characterization of
      isocyanate exposure in the autobody industry, was part of an epidemiologic study
      of workers in 37 autobody shops in Connecticut. This article describes
      workplaces, tasks, and controls, and outlines the frequency, duration, and
      intensity of isocyanate exposures. Personal air samples taken outside of
      respirators had median concentrations of 66.5 microg NCO/m3 for primer, 134.4
      microg (NCO)/m3 for sealer, and 358.5 microg NCO/m3 for clearcoat. Forty-eight
      percent of primer, 66% of sealer, and 92% of clearcoat samples exceeded the
      United Kingdom Health and Safety Executive guideline for isocyanate, though none
      exceeded the National Institute for Occupational Safety and Health (NIOSH)
      recommended exposure limit for monomer. Nonisocyanate-containing primers and
      sealers are used in more than half the shops, but nonisocyanate clearcoats are
      rare. Eighty-two percent of personal samples taken within a spray booth exceeded
      the U.K. guideline: 81% of those in downdraft spray booths, 74% in semidowndraft
      booths, and 92% in crossdraft booths. Only 8% of shops reported that spraying is
      done exclusively in spray booths. All painters wore some type of respirator. In
      30% of shops, painters used supplied air respirators; the rest relied on half
      face organic vapor cartridge respirators with N95 overspray pads. All shops
      provided some type of gloves, usually latex, not recommended for isocyanate
      protection. Despite improvements in autobody shop materials, practices, and
      controls, there are still opportunities for substantial exposures to isocyanates.

PMID- 15559330
TI  - Characterizing emission and breathing-zone concentrations following exposure
      cases to fluororesin-based waterproofing spray mists.
AB  - Measurements and simulations were performed to assess workers' exposure to
      solvent vapors and aerosols during the waterproofing of a tiled surface. This
      investigation followed two recent incidents in the same company where workers
      experienced acute respiratory illness after spraying a stain-repellent resin
      containing fluorinated polymers on stone-tiled walls and floors. Because the
      waterproofing activity had been done for years at the tile company without
      encountering any exposure problems prior to these cases, it was strongly
      suspected that the incidents were linked to a recent change in the composition of
      the coating mixture. Experimental measurements and simulations indicated that the
      emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec
      (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The
      measurement of the solvent emission rate from surfaces coated with the two resins
      indicated that shortly after spraying, the emission was in the range of 18 to 20
      mg/sec x m2 and was similar for both products. Solvent and overspray emission
      rates were introduced in a two-zone compartment model. The results obtained in
      the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3
      for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also
      shown that the introduction of the new resin tended to significantly decrease the
      levels of solvents and particulates in the workers' breathing zone. These results
      strongly suggest that cases of acute respiratory illness are related to the
      specific toxicity of the fluorinated polymer itself. The fact that the same
      polymer is used in various commercial products raises concern regarding other
      possible occupational and domestic exposures.

PMID- 15559331
TI  - Baseline measurements of smoke exposure among wildland firefighters.
AB  - Extensive measurements of smoke exposure among wildland firefighters are
      summarized, showing that firefighters can be exposed to significant levels of
      carbon monoxide and respiratory irritants, including formaldehyde, acrolein, and
      respirable particulate matter. Benzene was also measured and found to be well
      below permissible exposure limits, with the highest concentrations occurring
      among firefighters working with engines and torches burning petroleum-based fuel.
      Exposures to all pollutants were higher among firefighters at prescribed burns
      than at wildfires, while shift-average smoke exposures were lowest among
      firefighters who performed initial attack of wildfires in the early stages of the
      fires. Smoke exposure reaches its highest levels among firefighters maintaining
      fire within designated firelines and performing direct attack of spot fires that
      cross firelines. These events and the associated smoke exposures were positively
      correlated with increasing ambient wind speeds, which hamper fire management and
      carry the convective plume of the fire into firefighters' breathing zone. The
      pollutants measured in smoke were reasonably well-correlated with each other,
      enabling estimation of exposure to multiple pollutants in smoke from measurements
      of a single pollutant such as carbon monoxide.

PMID- 15559332
TI  - Assessment of the durability of medical examination gloves.
AB  - This study determined the durability of various types of medical examination
      gloves using a laboratory test developed by the researchers. Results of this
      testing are compared with a simulated clinical method, also developed by the
      researchers, found to produce failures at rates similar to actual clinical use.
      Ten types of exam gloves were tested. One set of gloves was tested using a glove
      durability method. A second set was worn and conditioned using a simulated
      clinical method for comparison. The third set consisted of a control set of
      gloves that were not stressed. Samples consisted of 100 gloves combined from 2 or
      4 manufacturers. All gloves were water-leak tested as the last step. The glove
      durability method created failures at similar rates to the simulated clinical
      method. The majority of the defects were located in the finger regions of the
      gloves. Durability of powdered and powder-free vinyl gloves was inferior to that
      of other glove types tested, with failure rates ranging from 24% to 42%, compared
      with 3% to 17% for the other glove types tested. Glove durability was also
      affected by the powdered state of the gloves and the user having long
      fingernails.

PMID- 15559333
TI  - Field method for the determination of insoluble or total hexavalent chromium in
      workplace air.
AB  - National Institute for Occupational Safety and Health method 7703 is a portable
      field procedure for the analysis of workplace air filter samples for hexavalent
      chromium (CrVI) content immediately after the samples are collected. The field
      method prescribes CrVI extraction from air filter samples with an ammonium
      sulfate/ammonium hydroxide extraction buffer using ultrasonic extraction (UE).
      Strong anion-exchange solid-phase extraction (SAE-SPE) is then used to separate
      CrVI from trivalent chromium and other interferences. Portable spectrophotometric
      measurement of CrVI is then conducted using the 1,5-diphenylcarbazide (DPC)
      method. However, it has been found that the ammonium extraction buffer does not
      adequately bring insoluble CrVI compounds into solution during the UE process.
      Thus, it was deemed necessary to modify the field method so that it would provide
      acceptable recoveries for insoluble CrVI compounds. To this end, a more alkaline
      extraction solution--sodium carbonate/sodium bicarbonate buffer--was
      investigated. The modified procedure using the highly alkaline extraction
      solution was demonstrated to be compatible with SAE-SPE cartridges when
      determining insoluble CrVI in air filter samples. It was found that the
      carbonate/bicarbonate buffer was equally effective for complete dissolution of
      both insoluble and soluble forms of CrVI. Furthermore, the modified procedure met
      desired performance criteria established for air sampling and analytical methods.

PMID- 15559334
TI  - Modeling the chemical protective performance of NBC clothing material.
AB  - The heat load, imposed by air-permeable NBC (nuclear, biological, and chemical)
      protective suits, can be reduced by improving the air permeability of the suit.
      However, increased air permeability will reduce the chemical protective
      performance, since increasing the air permeability of the NBC-protective material
      will result in higher air velocities through the material. In this study the
      relation between the chemical protective performance and air velocity through NBC
      clothing is evaluated. A theoretical model was developed that describes the
      chemical protection of air permeable NBC-protective clothing material under
      various conditions. The initial breakthrough concentration and the 50%
      breakthrough time are modeled as function of parameters like the air velocity and
      the challenge concentration. Using this model, the effect of airflow through the
      material on the breakthrough concentration of mustard vapor was calculated and
      compared with results of breakthrough experiments. The predictions of the model
      are in good agreement with the experimental results. The air velocity through the
      material and thus the air permeability of the material appear to be parameters of
      critical importance. High air velocity through the material results in high
      breakthrough concentrations, and therefore poor protective performance of the
      material. To describe the total breakthrough curve, a semiempirical model of
      experimental breakthrough results was made. This model describes the total
      breakthrough concentration of vapor through NBC-protective material as a function
      of parameters like the air velocity and the challenge concentration. This model
      can be used as a tool to optimise the protective performance of NBC-protective
      clothing material.

PMID- 15559335
TI  - Primary ovarian ectopic pregnancy.

PMID- 15559336
TI  - Primary peritoneal carcinoma.

PMID- 15559337
TI  - Ablative or excisional laparoscopic surgery for endometriotic cysts: resolving
      the issue.
AB  - A logistic regression analysis was carried out to compare laparoscopic excision
      with ablation for endometriotic cysts. Four comparative studies were identified.
      Cyst recurrence (%, +/- SE) was twice as likely after the ablation treatment
      (26.6% +/- 0.032) than after the excision treatment (13.2% +/- 0.019), (p <.001,
      relative risk 1.9). Two comparative studies were identified where postprocedure
      pregnancy rates were an outcome measure. Postoperative pregnancy rates were not
      significantly different for the ablation treatment (41.6% +/- 0.138) than for the
      excision treatment (56.9% +/- 0.23). There was only one comparative study to
      investigate symptom relief, therefore logistic regression analysis to compare
      studies was not possible. Three studies compared excisional surgery and
      perioperative medication with excisional surgery only. Cyst recurrence rates were
      not significantly different for the group that received medication (10.3% +/-
      0.033) than for the group that did not (4.0% +/- 0.02).

PMID- 15559338
TI  - Laparoscopic pelvic and paraaortic lymphadenectomy in gynecologic oncology.
AB  - In the early 1990s, different authors independently developed techniques for
      pelvic and paraaortic lymph node sampling. Since then, laparoscopic
      lymphadenectomy has been demonstrated to yield the same number of nodes when
      compared with the laparotomic approach. Only one microscopically involved lymph
      node was lost at laparoscopic lymphadenectomy when a laparotomic control followed
      immediately after. It seems bleeding, which is the most serious perioperative
      complication, is more common during laparoscopic lymphadenectomy than during
      laparotomy; however, the incidence will decrease with experience of the surgeon.
      The laparoscopic procedure does not seem to influence negatively the survival of
      patients with early stage endometrial and cervical cancer. There does not seem to
      be a significant reduction in overall hospital charges for laparoscopic surgery
      in oncology, but patients who undergo laparoscopic surgery recover significantly
      sooner than those who undergo laparotomy.

PMID- 15559339
TI  - Molecular characterization of postoperative adhesions: the adhesion phenotype.
AB  - Postoperative adhesion development remains a very frequent occurrence, which is
      often unrecognized by surgeons because of limited ability to conduct early second
      look laparoscopies. The consequences include infertility, pelvic pain, bowel
      obstruction, and difficult reoperative procedures. To date, approaches to limit
      adhesions primarily have involved barriers to separate tissue during
      reepithelization. Future progress in regulating adhesion development and tissue
      fibrosis likely will require an improved understanding of the molecular processes
      involved in normal peritoneal repair and its aberrations leading to adhesion
      development. We hypothesize that tissue hypoxia (in part resulting from tissue
      incision, fulguration, suture ligation, etc.) is the major inciting event, which
      leads to a coordinated series of molecular events that promote an inflammatory
      response leading to enhanced tissue fibrosis. These events are reduced
      plasminogen activator activity, extracellular matrix deposition, increased
      cytokine production, increased angiogenesis, and reduced apoptosis (programmed
      cell death). Improved understanding of these events and their regulation will
      provide the opportunity to regulate better postoperative adhesion development and
      tissue fibrosis, thereby reducing the morbidity and mortality they cause.

PMID- 15559340
TI  - Pain relief and outpatient hysteroscopy: a literature review.
AB  - Our early experience in setting up an ambulatory hysteroscopy service provoked a
      review of the literature, due to an unacceptably high failure rate. A literature
      review has been undertaken to establish the accepted success rates and reasons
      for failure, and to assess evidence for various analgesic protocols through
      randomized controlled trials. The data suggest the procedure is acceptable to
      most patients, with a completion success rate over 90%, and the use of analgesia
      may enhance the success rate. Analgesic protocols studied were nonsteroidal anti
      inflammatory drugs, intracervical block, paracervical block, transcervical block,
      and topical analgesia. Failures are due predominantly to pain, stenosis, and poor
      view.

PMID- 15559341
TI  - Randomization in controlled clinical trials: why the flip of a coin is so
      important.
AB  - The randomized controlled trial (RCT) is considered the highest level of medical
      evidence. In this brief overview, we discuss several key principles of the RCT.
      First, balance is paramount. Comparison groups must have similar proportions of
      participants with "important" prognostic and confounding factors. Randomization
      may or may not achieve this balance; if it does not, statistical adjustments
      should be used. Second, a statistical analysis should emphasize comparability and
      not mask dissimilarity. If the trial was indeed randomized, certain analysis
      techniques, such as an intention to treat analysis, should always be presented.
      Third, additional bias-reducing techniques, such as concealing treatment
      assignments from treating physicians and participants (i.e., masking) and using
      clearly defined exclusion and inclusion criteria, should be used wherever
      possible.

PMID- 15559342
TI  - LUCY: a 3-D pelvic model for surgical simulation.
AB  - Development of 3-D models of human anatomy for use in virtual reality simulators
      is anticipated to enhance surgical training. These models may be a valuable
      resource for gaining mastery of minimal-access procedures. The pelvis portion
      (hip to upper-thigh) of a 32-year-old female cadaver was frozen and sectioned
      axially in approximately 2-mm increments as the first step in producing an
      accurately representative 3-D model of the human female pelvis. Photographic
      exposures of the entire series of 95 sections were then converted to digital
      format. Adobe PhotoShop masks for each structure were created and converted into
      wire-frame and surface-textured models; this aggregate model set was named
      "LUCY." To date, 3-D representations of 40 pelvic structures (over 2200
      individual masks) have been modeled In conjunction with haptic technology, these
      virtual anatomic models will enable users to practice fundamental surgical
      manipulations and procedures such as tubal ligation and ovariectomy. The
      deployment of surgical-simulation models such as LUCY may facilitate technical
      performance aspects of surgical training, particularly those associated with
      minimal-access procedures. Manipulations and procedures can be practiced over the
      Internet, providing a host of flexible options to enhance the surgical curricula.

PMID- 15559343
TI  - Laparoscopic treatment of pelvic floor defects in women of reproductive age.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of conservative laparoscopic treatment
      of genital prolapse in women of reproductive age. DESIGN: Retrospective analysis
      (Canadian Task Force classification II-2). SETTING: University hospital, Center
      of Reconstrutive Pelivc Endosurgery, Reproductive Medical Unit, S. Orsola
      Hospital, Bologna, Italy. PATIENTS: Fifteen women of reproductive age with
      genital prolapse. Interventions. Conservative laparoscopic surgical correction of
      genital prolapse. Apical prolapse was corrected by sacral colpohysteropexy. Burch
      colposuspension was always included to treat evident or latent stress urinary
      incontinence. Anterior compartment defects were treated by laparoscopic
      paravaginal repair and by the interposition of an intervesicouterine prosthesis.
      Posterior compartment defects were corrected by a prosthetic reconstruction of
      the rectovaginal support structure. MEASUREMENTS AND MAIN RESULTS: All patients
      underwent surgery between January 1998 and December 2000. They were prospectively
      evaluated for a minimum of 24 months of follow-up. No woman underwent additional
      surgery during the follow-up period. All women had resolution of the apical
      prolapse. In one woman, anterior compartment correction (i.e., correction of the
      anterior part of endopelvic fascia, including correction of bladder and anterior
      vaginal wall prolapse) was reported. No woman underwent additional prolapse
      surgery during the follow-up period. Three women became pregnant after surgery:
      one had an abortion at 8 weeks' gestation; the other two completed term
      pregnancies and delivered by cesarean section. CONCLUSION: Laparoscopic therapy
      of genital prolapse is a desirable procedure in patients of reproductive age
      because it respects the anatomic structures and maintains the function of the
      organs. Furthermore, laparoscopic treatment is feasible and well-tolerated and
      produces good results.

PMID- 15559344
TI  - Adnexal torsion after laparoscopic hysterectomy: description of seven cases.
AB  - STUDY OBJECTIVE: To discover the prevalence of adnexal torsion after laparoscopic
      hysterectomy. DESIGN: Retrospective analysis (Canadian Task Force classification
      II-3). SETTING: A tertiary referral hospital. PATIENTS: One thousand thirty-three
      women underwent laparoscopic hysterectomies between the years 1995 and 2002. The
      mean age (+/- SD) of the women at the time of hysterectomy was 43.87 +/- 4.28
      years. Intervention. Laparoscopic hysterectomy in which at least one adnexa was
      left intact. MEASUREMENTS AND MAIN RESULTS: The files of all women with adnexal
      torsion diagnosed by laparoscopy from 1995 to 2003 were retrospectively reviewed.
      In seven women, adnexal torsion occurred after laparoscopic hysterectomy. Torsion
      occurred 2.64 (+/- 1.79) years (mean +/- SD) after hysterectomy. Torsion was
      treated by laparoscopy in all of the women; either oophorectomy or detorsion and
      ovariopexy was performed. We calculated the prevalence of this complication to be
      7.91/1000. CONCLUSION: Adnexal torsion can occur after laparoscopic hysterectomy.

PMID- 15559345
TI  - Abnormal uterine bleeding: medical treatment with vaginal danazol and five-year
      follow-up.
AB  - STUDY OBJECTIVE: To evaluate the clinical efficacy and patient satisfaction of
      long-term danazol delivered vaginally as treatment for heavy menstrual bleeding.
      DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING:
      University hospital. PATIENTS: Twenty premenopausal women with endometrial
      hyperplasia or endometrial polyps. INTERVENTION: After curettage or hysteroscopic
      directed biopsies, women used one 200-mg tablet of danazol vaginally every day,
      continuing the therapy as long as they were totally satisfied with it.
      MEASUREMENTS AND MAIN RESULTS: Women were instructed to keep a diary of menstrual
      bleeding and to rate blood loss on a visual analog scale from zero (no blood
      loss) to 10 (gushing-type bleeding). They were seen every month for 3 months,
      then every 3 months for 9 months, and then every 6 months for 4 years for
      Papanicolau smear, pelvic examination, and transvaginal ultrasonography. They
      were asked to bring their diary of menstrual bleeding. They were asked about side
      effects and their satisfaction with the therapy. Peripheral blood was drawn for
      blood count and serum chemistries. Hysteroscopic-directed biopsies were repeated
      after 3 months of therapy in women with endometrial hyperplasia. The severity of
      blood loss was significantly reduced in all women after 3 months of treatment.
      All women with endometrial hyperplasia had regression of hyperplastic
      endometrium. None of the women with endometrial polyps had sonographic signs of
      recurrence during therapy. Only 10 women (50%) completed 1-year follow-up, and
      only 5 women (25%) completed 5-year follow-up. CONCLUSION: These results suggest
      that long-term administration of vaginal danazol after curettage or hysteroscopic
      directed biopsy is both efficacious and safe in women with heavy menstrual
      bleeding, but the rate of discontinuance is high.

PMID- 15559346
TI  - Bipolar electrocoagulation versus suture of solitary ovary after laparoscopic
      excision of ovarian endometriomas.
AB  - STUDY OBJECTIVE: To compare the functional ovarian damage associated with the use
      of bipolar coagulation versus ovarian suture after laparoscopic excision of
      ovarian endometriomas in patients with a solitary ovary. DESIGN: Retrospective
      study (Canadian Task Force classification II-3). SETTING: Tertiary care center.
      PATIENTS: Forty-seven consecutive women with a single ovary and regular menses
      who underwent laparoscopic stripping of one or more ovarian endometriomas between
      June 1996 and June 2001. Intervention. Twenty-one patients had bipolar
      electrocoagulation (group A), while 26 had suturing of the ovary (group B).
      Plasma follicle-stimulating hormone (FSH) and estradiol levels were determined
      before surgery and re-evaluated at 3-, 6-, and 12-month follow-up. MEASUREMENTS
      AND MAIN RESULTS: At 12-month follow-up, six patients (29%) in group A had oligo
      amenorrhea versus three patients (12%) in group B (p = .14). Follicle-stimulating
      hormone levels between 10 and 20 mlU/mL were found in five patients (24%) in
      group A and in three patients (12%) in group B, whereas FSH levels above 20
      mlU/mL were found in three patients (14%) in group A and in no patient in group
      B. Eight patients (38%) in group A had FSH levels greater than 10 mlU/mL versus
      three patients (12%) in group B (p = .042). Overall, repeated analysis of
      variance showed a marginally significant difference (p = .06) in FSH values
      between the two groups. CONCLUSION: Our results suggest that bipolar
      electrocoagulation of the ovarian parenchyma after laparoscopic stripping of an
      endometriotic ovarian cyst adversely affects ovarian function.

PMID- 15559347
TI  - Ovarian function after uterine artery embolization and hysterectomy.
AB  - STUDY OBJECTIVE: To evaluate the effect of uterine artery embolization (UAE) and
      hysterectomy on ovarian function. DESIGN: Prospective case control study
      (Canadian Task Force classification II-2). SETTING: University teaching hospital.
      PATIENTS: Eighty-four healthy premenopausal women with symptomatic uterine
      myoma(s) undergoing UAE or hysterectomy. INTERVENTION: Patients had blood drawn
      to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      estradiol (E2) levels and underwent transvaginal ultrasound to measure volume of
      the myoma(s) and uterus on cycle day 3 before the procedures. These measurements
      were repeated 3 and 6 months after treatment. MEASUREMENTS AND MAIN RESULTS: The
      main outcome was the differences in serum FSH, LH, E2, and ultrasound findings
      before and after UAE or hysterectomy. Of the 68 patients who underwent UAE and 16
      who underwent hysterectomy, 48 and 13 respectively, completed 6-month follow-up.
      The mean age of the patients in the UAE group was 44.9 +/- 3.8 years and 43.7 +/-
      5.6 years in the hysterectomy group. There was no significant difference in serum
      FSH before (8.9 +/- 0.7 IU/L) and 6 months after UAE (9.9 +/- 1.0 lU/L), and
      between the baseline (10.4 +/- 1.8 lU/L) and 6 months posthysterectomy (7.8 +/-
      1.8 lU/L). The uterine volume 6 months after UAE (361 +/- 50 mL) was
      significantly smaller than before UAE(538 +/- 38mL; p =.005, 95% CI 44-241).
      Compared with baseline (154 +/- 20 mL), the dominant myoma volume was smaller at
      6 months after UAE (97 +/- 16 mL; p <.05, 95% CI 1.57-62). CONCLUSION: Uterine
      artery embolization is associated with a significant reduction in myoma and
      uterine volume. Ovarian function at 6 months, as indicated by day 3 FSH levels,
      is not affected by UAE or hysterectomy.

PMID- 15559348
TI  - The suburethral sling for female stress urinary incontinence: a retropubic or
      obturator approach?
AB  - STUDY OBJECTIVE: To evaluate the feasibility and safety of the obturator approach
      for placement of a vaginal suburethral sling indicated for women with stress
      urinary incontinence. DESIGN: Retrospective cohort analysis (Canadian Task Force
      classification IV). SETTING: University teaching hospital. PATIENTS: Forty-nine
      women suffering from stress incontinence. INTERVENTION: Analysis of the
      suburethral sling according to surgical approach during two consecutive periods:
      retropubic from January 1, 2001 through September 30, 2001, and obturator from
      October 1, 2001 through January 31, 2002. MEASUREMENTS AND MAIN RESULTS: During
      the study period, 25 patients underwent surgery with the retropubic approach and
      24 with the obturator approach. The patient characteristics did not differ
      between the two groups. The obturator approach was feasible in all attempted
      procedures. The mean operative time was 46 minutes (range 20-90) for the
      retropubic approach compared with 32 minutes (range 15-50) for the obturator
      approach (p = .03). Two bladder injuries occurred with the former, none with the
      latter (although cystoscopy was not routinely performed) (p = .49). Similarly,
      significantly more patients in the retropubic approach group had difficulty with
      postoperative voiding compared with those in the obturator approach group (10
      [40%] vs 2 [8%], p = .01). Only two patients, both in the retropubic group, had
      voiding difficulties for longer than 1 week. One month after surgery, continence
      results did not differ significantly between the two groups (p = .30). In the
      retropubic approach group, 20 (80%) of the women were cured, and substantial
      improvement was experienced by 5 (20%). In the obturator approach group, these
      figures were 20 (83%) and 3 (12.5%), respectively, with one surgical failure
      (4%). Those initial results were unchanged at last follow-up (mean follow-up was
      13.7 +/- 3 months for the retropubic approach group and 7.2 +/- 2 months for the
      obturator approach group). CONCLUSION: The obturator approach for suburethral
      slings is feasible and safe and may limit both preoperative and postoperative
      complications. Our short-term continence results compare well with those achieved
      with the retropubic approach. A randomized study is now needed to compare these
      two approaches.

PMID- 15559349
TI  - Outpatient laparoscopic hysterectomy in a rural ambulatory surgery center.
AB  - STUDY OBJECTIVE: To evaluate a cost-optimized operative technique for outpatient
      laparoscopic hysterectomy in a rural ambulatory surgery center focusing on
      shortening hospital stay and substitution of expensive disposable laparoscopic
      instruments with standard surgical techniques. DESIGN: Prospective feasibility
      and observational study (Canadian Task Force classification II-3). SETTING: Rural
      ambulatory surgery center in Lamar, Alabama. PATIENTS: Fifty-two women.
      INTERVENTION: Outpatient laparoscopic hysterectomy. MEASUREMENTS AND MAIN
      RESULTS: From September 2001 through September 2003, 52 consecutive procedures
      with a modified classical intrafascial supracervical hysterectomy (CISH)
      technique without disposable instruments have been performed on patients with an
      average age of 42.2 years (range 25-62 years) and a follow-up of 12.5 months
      (range 0.4-23.6 months). Mean postoperative length of stay was 6 hours, 79
      minutes (range 3 hours, 10 minutes-17 hours, 30 minutes), and overall length of
      stay was 11 hours, 37 minutes (range 6 hours, 45 minutes-22 hours, 50 minutes).
      Five patients (9.6%) stayed overnight, three for medical and two for social
      reasons. With an average of 2 hours, 14 minutes, the operating room time was
      about 1 hour longer than with disposable instruments. Health insurance
      reimbursement for the ambulatory surgery center was on average $1814.11. No
      complications occurred, and no readmission to the hospital was necessary.
      CONCLUSION: Outpatient laparoscopic hysterectomy is feasible and safe and can be
      performed cost effectively in ambulatory surgery centers, even in rural areas.
      Development of a protocol with patient selection, preoperative and postoperative
      patient teaching, caring family environment, and round-the-clock medical
      telephone backup is necessary.

PMID- 15559350
TI  - Frozen section in laparoscopic management of macroscopically suspicious ovarian
      masses.
AB  - STUDY OBJECTIVE: To study the usefulness of and applications for frozen section
      in the laparoscopic management of adnexal masses. DESIGN: Historical prospective
      study (Canadian Task Force classification II-3). SETTING: Large tertiary care
      hospital with university affiliation. PATIENTS: One hundred forty-one women
      undergoing laparoscopy for a suspicious adnexal mass. INTERVENTION: Adnexal
      masses suspicious on ultrasound were managed by laparoscopy. After laparoscopic
      diagnosis, frozen sections were used to confirm a diagnosis of malignancy.
      Treatment was performed by laparoscopy whenever feasible. MEASUREMENTS AND MAIN
      RESULTS: The results of frozen section were compared with the results of
      permanent sections, and the consequences of the intraoperative diagnosis on the
      surgical management were evaluated. The frozen section diagnosis was correct in
      125 of the 141 patients (88.7%). In one patient, the result was false negative.
      Specifically, frozen section diagnosis was correct in 96.8% of cases when a cyst
      or biopsy was sent for pathologic examination and in 86.4% when the whole adnexa
      was sent. It was correct in 93% of the cases involving tumors smaller than 100 mm
      and in 74% of larger tumors. It was correct in 92.3% of the women younger than 50
      years and in 81.6% of women older than age 50. Intraoperative pathologic
      diagnosis was correct in 95.5% of benign tumors, 77.8% of low-malignancy tumors,
      and 75% of cancer cases. CONCLUSION: Frozen section is a useful examination for
      surgical management decision making; however, the limitations and the
      difficulties should be taken into account.

PMID- 15559351
TI  - A simplified method to decrease operative blood loss in laparoscopic-assisted
      vaginal hysterectomy for the large uterus.
AB  - STUDY OBJECTIVE. To evaluate the role of oxytocin in decreasing operative blood
      loss in laparoscopic-assisted vaginal hysterectomy (LAVH) for the large uterus
      (weight > or = 500 g). DESIGN: Prospective clinical study (Canadian Task Force
      classification II-2). SETTING: Tertiary care university hospital. PATIENTS:
      Eighty-eight women scheduled for a hysterectomy for large benign uterine tumors.
      INTERVENTION: Two ampules of oxytocin (10 u/mL/amp) were added to 1000 mL of
      saline solution running at the rate of 40 mU/min during the course of LAVH.
      MEASUREMENTS AND MAIN RESULTS: Blood loss and blood transfusion rate were
      significantly greater in the group without oxytocin infusion (group B) than in
      the group with oxytocin infusion (group A), with 485.7 +/- 321.6 mL versus 364.1
      +/- 173.2 mL (p <.05) and 26.7% versus 6. 1% (p <.05), respectively. There was no
      significant difference in average age, body weight, and number of vaginal
      deliveries and cesarean sections between the two groups. There also was no
      significant difference in mean uterine weight, postoperative stay, and
      complications between the two groups. CONCLUSION: Oxytocin infusion can cause
      uterine contractions that decrease uterine perfusion. It is a safe and
      inexpensive method to help decrease operative blood loss during LAVH for the
      large uterus.

PMID- 15559352
TI  - Fertility after ovarian drilling by transvaginal fertiloscopy for treatment of
      polycystic ovary syndrome.
AB  - STUDY OBJECTIVE: To evaluate fertiloscopy ovarian drilling with bipolar energy in
      women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). DESIGN:
      Prospective study (Canadian Task Force classification II). SETTING: University
      teaching hospital and private clinic. PATIENTS: Eighty women with clomiphene
      citrate-resistant PCOS. INTERVENTION: Operative transvaginal fertiloscopy with a
      coaxial bipolar electrode. MEASUREMENTS AND MAIN RESULTS: During a mean follow-up
      of 18.1 months (+/- 6.4), 73 women (91%) recovered regular and ovulatory cycles.
      The cumulative pregnancy rate was 60% (44/73) for spontaneous and stimulated
      cycles, with 39.7% (29/73) imputed to drilling alone. The mean time to conceive
      was 3.9 months (range 1-11.8). There were eight miscarriages (18%), and no
      ectopic pregnancies or multiple pregnancy. No complications occurred. CONCLUSION:
      Ovarian drilling by transvaginal fertiloscopy with bipolar electrosurgery appears
      to be an effective minimally invasive procedure in patients with PCOS resistant
      to clomiphene citrate.

PMID- 15559353
TI  - Capacitive coupling: a comparison of measurements in four uterine resectoscopes.
AB  - STUDY OBJECTIVE: To compare electrosurgical waveform and electrode integrity as
      variables in the capacitive induction of current to the external sheath of four
      different resectoscopes. DESIGN: Laboratory comparative study. SETTING: Surgical
      laboratory. INSTRUMENTATION: Valleylab Force FX and Force 4 radiofrequency (RF)
      electrosurgical units (ESUs); resectoscopes from four manufacturers; and
      rollerball electrodes, both intact and with standardized insulation defects. The
      ESU was fired over a working range of high- and low-voltage outputs in open
      circuit conditions, and current and wattage were measured and recorded from both
      the electrodes and the external sheath. MEASUREMENTS AND MAIN RESULTS: With
      intact insulation, relatively little current was measurable on the external
      sheath of any of the resectoscopes regardless of the power or waveform. However,
      with high-voltage outputs, most proximal insulation defects, and some distal
      defects, a large proportion of ESU output was measured on the external sheath.
      There were no such findings with any resectoscope, at any power setting or with
      any insulation defect, with low-voltage ("cutting") outputs. CONCLUSIONS: These
      results confirm that high-voltage outputs may present a greater risk for current
      diversion to the external sheath of any of the monopolar resectoscopes tested and
      that this could contribute to the risk of lower genital tract injury during RF
      resectoscopic surgery.

PMID- 15559354
TI  - Essure hysteroscopic sterilization: results based on utilizing a new coil
      catheter delivery system.
AB  - STUDY OBJECTIVE: To assess the safety and placement effectiveness of a new
      delivery catheter for the Essure micro-insert hysteroscopic sterilization system.
      DESIGN: Prospective, multicenter, single-arm clinical study. (Canadian Task Force
      classification II-3). SETTING: Hospital-based clinical research centers.
      PATIENTS: One hundred two women of reproductive age and proven fertility.
      INTERVENTION: A new coil catheter delivery system was used for micro-insert
      placement. MEASUREMENTS AND MAIN RESULTS: The bilateral placement of micro
      inserts using the coil catheter delivery system occurred in 100 women out of 102
      attempts (98%). The two women who did not have successful micro-insert placement
      were subsequently shown to have proximal tubal stenotic disease. CONCLUSION:
      These findings indicate that the introduction of the coil catheter delivery
      system for Essure hysteroscopic sterilization improves the micro-insert bilateral
      placement rate when compared with previous studies. It is hypothesized that the
      coil catheter has superior navigational properties, particularly within tortuous
      or narrowed tubal lumens.

PMID- 15559355
TI  - Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a
      multicenter randomized trial.
AB  - STUDY OBJECTIVE: To compare the effectiveness, safety, and acceptability of
      microwave endometrial ablation (MEA) with those of rollerball electroablation
      (REA) for the treatment of menorrhagia. DESIGN: Randomized clinical trial
      (Canadian Task Force classification I). SETTING: Eight academic medical centers
      and private medical practices. PATIENTS: Three hundred twenty-two women with
      documented menorrhagia due to benign causes. INTERVENTION: MEA or REA.
      MEASUREMENTS AND MAIN RESULTS: By intent-to-treat analysis, the success rate of
      MEA at 12 months (87.0%; CI 81.7%-91.2%) did not differ significantly (p = .40)
      from that of REA (83.2%; CI 74.7%-89.7%). Among evaluable patients, success rate
      was also similar (p = .24) in the MEA (96.4%; CI 92.7%-98.5%) and REA (92.7%; CI
      85.6%-97%) groups. The amenorrhea rate in evaluable patients after MEA was 61.3%
      (CI 54.1 %-68.2%). In patients with myomas, the success and amenorrhea rates in
      evaluable patients after MEA were 90.3% (CI 74.2%-98%) and 61.3% (CI 42.2%
      78.2%), respectively. In evaluable patients with body mass index of 30 kg/m2 or
      greater, MEA success rate was 96.7% (CI 88.5%-99.6%) compared with 81.8% (CI
      59.7%-94.8%) for REA (p = .042). The ablation procedure was performed under IV
      sedation in 62% of patients in the MEA group versus 18% of patients in the REA
      group (p <.001); whereas, general anesthesia was employed more often in patients
      undergoing REA (37% vs. 76%, p <.001). No major complications were encountered.
      Patient satisfaction with results of treatment was high (98.5% of the MEA and
      99.0% of the REA group). CONCLUSIONS: Microwave endometrial ablation is an
      efficacious and safe procedure for the treatment of menorrhagia. Over half of
      patients treated with MEA achieve amenorrhea, and the procedure is suitable for
      women with myomas and irregular uterine cavities. The procedure is easily learned
      and can be performed rapidly, under IV sedation in most cases.

PMID- 15559356
TI  - Preoperative evaluation of submucosal myoma by virtual hysteroscopy.
AB  - STUDY OBJECTIVE: To assess the utility of a new technique called virtual
      hysteroscopy in the evaluation of the size and location of submucosal myomas
      before hysteroscopic myomectomy. DESIGN: Retrospective analysis (Canadian Task
      Force classification II-1). SETTING: Department of gynecology at a general
      hospital. PATIENTS: Thirteen consecutive women. INTERVENTION: Sixteen-slice
      computed tomography (CT) scanner. MEASUREMENTS AND MAIN RESULTS: Thirteen women
      with submucosal myomas were examined by virtual hysteroscopy. The lesions were
      filmed by multislice CT scanner, immediately after CO2 injection into the uterine
      cavity with an intravenous dosage of iodide contrast media. The filmed image was
      subsequently reconstituted and analyzed by endoscopy mode and volume mode using
      three-dimensional computer graphics software. The size and depth of invasion of
      the submucosal myoma were clearly identified by the procedure. CONCLUSION:
      Accurate preoperative evaluation of the size and location of submucosal myomas
      before hysteroscopic myomectomy is important for a safe surgical procedure.
      Virtual hysteroscopy can provide such information with good reproducibility and
      is superior to previously described diagnostic procedures.

PMID- 15559357
TI  - Twenty-five simple ways to increase insufflation performance and patient safety
      in laparoscopy.
AB  - Technical aspects of laparoscopic insufflation technique and interaction among
      patient, technique, and physician can affect the performance of laparoscopy and
      patient safety. A variety of laparoscopic equipment was evaluated regarding
      insufflation performance in laboratory measurements and/or in an intraoperative
      computer-based data-acquisition model for intraabdominal pressure, gas flow, and
      temperature. In this article, we present 25 suggestions for improving
      insufflation performance and increasing patient safety. These tips may help avoid
      and solve insufflation problems and malfunction, over- and under-pressure peaks,
      laparoscopic hypothermia, and gas embolism, and shorten operation room and
      anesthesia time, thereby saving time, money, and physician stress.

PMID- 15559358
TI  - Intestinal adhesion to the abdominal wall after skin closure with
      octylcyanoacrylate.
AB  - Octylcyanoacrylate tissue adhesive glue is a wound closure device recently
      approved by the U.S. Food and Drug Administration. Few complications have been
      reported regarding the liquid adhesive entering the wound. The following report
      involves a patient who developed intestinal occlusion secondary to
      octylcyanoacrylate used for skin closure in laparoscopic surgery.

PMID- 15559359
TI  - Vulvar edema as a rare complication of laparoscopy.
AB  - Vulvar edema as a complication of laparoscopy is a rare condition. A 23-year-old
      woman was admitted with progressive dysmenorrhea and underwent laparoscopic
      bilateral endometrioma cystectomy. Twenty-seven hours after surgery, unilateral
      vulvar edema was observed. It resolved with the application of ice packs and
      insertion of a Foley catheter. We conclude that this is a rare, normally benign
      condition that is easy to manage.

PMID- 15559360
TI  - Ectopic pregnancy in an inguinal herniorrhaphy scar.
AB  - An ectopic pregnancy may occur in unusual sites. In the following case, an
      ectopic pregnancy was discovered in the first trimester within an inguinal
      herniorrhaphy scar from an inguinal herniorrhaphy performed about 20 years
      previously. Early diagnosis of the ectopic pregnancy by sonography enabled
      laparoscopic management and preservation of the woman's fertility.

PMID- 15559361
TI  - Deeply infiltrating endometriosis originates from the retrocervical area.

PMID- 15559362
TI  - Comments on laparoscopic excision of myometrial adenomyomas in patients with
      adenomyosis uteri and main symptoms of severe dysmenorrhea and hypermenorrhea.

PMID- 15559363
TI  - On the mechanisms of the protective effect of infections on type 1 diabetes.
AB  - The incidence of type 1 diabetes (T1D) shows a worrying tendency for a steady
      increase in Western countries. Along the line of the hygiene hypothesis, evidence
      accumulates to suggest that this increase is explained by the decrease of
      infections due to improved hygiene and medical care. This article presents a
      review of epidemiological data and of the main putative underlying cellular and
      molecular mechanisms.

PMID- 15559364
TI  - Inflammatory bowel disease: autoimmune or immune-mediated pathogenesis?
AB  - The pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), the two
      main forms of inflammatory bowel disease (IBD), is still unclear, but both
      autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena
      include the presence of serum and mucosal autoantibodies against intestinal
      epithelial cells in either form of IBD, and against human tropomyosin fraction
      five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic
      antibodies (pANCA) are common in UC, whereas antibodies against Saccharomyces
      cerevisiae (ASCA) are frequently found in CD. Immune-mediate phenomena include a
      variety of abnormalities of humoral and cell-mediated immunity, and a generalized
      enhanced reactivity against intestinal bacterial antigens in both CD and UC. It
      is currently believed that loss of tolerance against the indigenous enteric flora
      is the central event in IBD pathogenesis. Various complementary factors probably
      contribute to the loss of tolerance to commensal bacteria in IBD. They include
      defects in regulatory T-cell function, excessive stimulation of mucosal dendritic
      cells, infections or variants of proteins critically involved in bacterial
      antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

PMID- 15559365
TI  - A review of the physiological and immunological functions of biliary epithelial
      cells: targets for primary biliary cirrhosis, primary sclerosing cholangitis and
      drug-induced ductopenias.
AB  - Our understanding of biliary epithelial cells (BEC) in physiobiology and
      immunology has steadily expanded. BEC transports IgA as well as IgM into bile,
      synthesizes and secretes various chemokines, cytokines, and expresses adhesion
      molecules involved in cell interaction and signal transduction. These then
      suggest a myriad of potential roles for BEC in defense from invading
      microorganisms as well as the pathogenesis of diverse immunologically driven
      diseases such as primary biliary cirrhosis (PBC), graft-versus-host disease, and
      primary sclerosing cholangitis (PSC). Despite the progress, there still remain
      many areas of BEC biology that require further investigation. Most importantly,
      it remains to be clarified that the extent to which the immunologic activities
      observed in BEC represent a BEC response to tissue injury or whether BEC
      themselves are the active participants in the pathogenesis of various cholestatic
      immunological diseases, including PBC and PSC.

PMID- 15559366
TI  - The intrathymic pathogenesis of myasthenia gravis.
AB  - The thymus is considered to play an important role in the pathogenesis of
      Myasthenia gravis, an autoimmune disease characterized by antibody-mediated
      skeletal muscle weakness. However, its role is yet to be defined. The studies
      described herein summarize our efforts to determine how intrathymic expression of
      the neuromuscular type of acetylcholine (ACh) receptors is involved in the
      immunopathogenesis of this autoimmune disease. We review the work characterizing
      the expression of neuromuscular ACh receptors in the thymus and advance a new
      hypothesis that examines the intrathymic expression of this autoantigen in
      disease pathogenesis.

PMID- 15559367
TI  - C-reactive protein (CRP) and autoimmune disease: facts and conjectures.
AB  - C-reactive protein (CRP) is a blood component comprised of five identical
      subunits with a combined molecular mass of 110 kDa; in the presence of Ca++ it
      binds phosphocholine (PC) with high affinity. Ligand-bound CRP activates
      complement and the protein reportedly binds various Fc receptors. Coincident with
      a now decade-long resurgence in clinical interest in associations of CRP with
      disease, our laboratory has been investigating the biology of CRP in vivo using
      human CRP transgenic mice (CRPtg). At that time we confirmed that CRP affects a
      host defense function mediated at least in part through the elimination of
      pathogens. Less appreciated and not as well understood as CRP's ability to bind
      antigen and aid in the elimination of microbes, is its known ability to bind
      autoantigens and presumed capacity to promote clearance of apoptotic cells. These
      latter properties of CRP have long been suspected to contribute to homeostasis
      and to autoimmune disease. In this article we review and update the evidence
      generated in CRPtg by our group and in vitro by others' that indicates CRP is
      more than just an antimicrobial molecule and convenient marker of inflammation
      rather, it protects against autoimmunity. A mechanistic hypothesis is presented
      to account for this cause-and-effect relationship.

PMID- 15559368
TI  - Virus-induced systemic vasculitides: new therapeutic approaches.
AB  - The best therapeutic strategy in virus-induced vasculitides should take into
      account the etiology of the disease and be adapted to the pathogenesis. The
      combination of antiviral treatments and plasma exchanges has been proven
      effective in polyarteritis nodosa (PAN). In human immunodeficiency virus (HIV)
      related vasculitis this strategy is also effective and does not jeopardize, like
      cytotoxic agents, the outcome of AIDS. In vasculitis related to HCV-associated
      cryoglobulinemia, plasma exchanges improve the outcome but the poor effectiveness
      of antiviral drugs is not able to favor, usually, a definite recovery of the
      patients and relapses are frequent.

PMID- 15559369
TI  - Plasmin promotes keratinocyte migration and phagocytic-killing accompanied by
      suppression of cell proliferation which may facilitate re-epithelialization of
      wound beds.
AB  - Keratinocytes were shown to induce the activation of plasminogen activator
      resulting in the formation of plasmin and the initiation of proteolysis in vitro.
      Activation of surface bound plasminogen may localize protease activity in the
      pericellular microenvironment and play a role in inducing both a conformational
      change and cell locomotion. Plasmin, however, can induce non-proteolytic effects
      on certain cell functions in a variety of cell lineages. In the present study we
      examined the effects of plasmin on keratinocytes with a focus on its role in the
      process of re-epithelialization, which included studies of cell migration,
      phagocytic-killing and cell proliferation. Migration of freshly isolated human
      epidermal keratinocytes was analyzed utilizing the agarose gel assay in the
      presence of 10% human serum. Plasmin at the concentration of 25 U/I induced a
      160% increase in the chemotactic migration of keratinocytes that was completely
      blocked by the plasmin inhibitor alpha2-antiplasmin (Serpin). In the absence of
      serum, plasmin also induced a reversible chemotactic migration of HaCaT
      keratinocytes as determined utilizing the microchemotaxis assay. Dose-response
      analysis showed a bi-phasic effect of plasmin with a maximum increase of 52% in
      keratinocyte chemotaxis at a concentration of 25 U/I. HaCaT cells on the other
      hand, showed no detectable in vitro chemokinesis by plasmin. Phagocytic-killing
      of Candida albicans by freshly isolated epidermal keratinocytes was enhanced in
      the presence of 25 U/I plasmin which was also reversible by the addition of
      Serpin. Spontaneous proliferation of HaCaT keratinocytes as determined by 3H
      Thymidine uptake on the other hand, was reduced by 47 and 13% in cultures with 25
      U/I plasmin for 24 and 48 h respectively, in a Serpin reversible manner. These
      data suggest that plasmin-induced chemotactic migration of epidermal
      keratinocytes is accompanied by enhanced phagocytic-killing coupled with
      suppression of proliferation of these cells which may facilitate re
      epithelialization following skin injury.

PMID- 15559370
TI  - Autoimmune epilepsy: some epilepsy patients harbor autoantibodies to glutamate
      receptors and dsDNA on both sides of the blood-brain barrier, which may kill
      neurons and decrease in brain fluids after hemispherotomy.
AB  - PURPOSE: Elucidating the potential contribution of specific autoantibodies (Ab's)
      to the etiology and/or pathology of some human epilepsies. METHODS: Six epilepsy
      patients with Rasmussen's encephalitis (RE) and 71 patients with other epilepsies
      were tested for Ab's to the "B" peptide (amino acids 372-395) of the
      glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA),
      and additional autoimmune disease-associated autoantigens, and for the ability of
      their serum and cerebrospinal-fluid (CSF) to kill neurons. RESULTS: Elevated anti
      GluR3B Ab' s were found in serum and CSF of most RE patients, and in serum of
      17/71 (24%) patients with other epilepsies. In two RE patients, anti-GluR3B Ab's
      decreased drastically in CSF following functional-hemispherotomy, in association
      with seizure cessation and neurological improvement. Serum and CSF of two RE
      patients, and serum of 12/71 (17%) patients with other epilepsies, contained
      elevated anti-dsDNA Ab's, the hallmark of systemic-lupus-erythematosus. The sera
      (but not the CSF) of some RE patients contained also clinically elevated levels
      of "classical" autoimmune Ab's to glutamic-acid-decarboxylase, cardiolipin, beta2
      glycoprotein-I and nuclear-antigens SS-A and RNP-70. Sera and CSF of some RE
      patients caused substantial death of hippocampal neurons. CONCLUSIONS: Some
      epilepsy patients harbor Ab's to GluR3 and dsDNA on both sides of the blood-brain
      barrier, and additional autoimmune Ab's only in serum. Since all these Ab's may
      be detrimental to the nervous system and/or peripheral organs, we recommend
      testing for their presence in epilepsy, and silencing their activity in Ab
      positive patients.

PMID- 15559371
TI  - Early appearance of TNF-alpha and other cytokines in bronchus associated lymphoid
      tissues (BALT) from growing Wistar rats. what is the role of TNF-alpha?
AB  - Several different cytokines trigger the development of determined cell subsets in
      BALT of growing Wistar rats. Early appearance (4 days post partum) of gammadeltaT
      cells in BALT has been shown, as well as its role in up-regulating TNF-alpha
      production. In the present report, we studied in the BALT: (1) the profile of the
      cytokines, TNF-alpha, INF-alpha and IL-10 and (2) in TCR gammadelta+ cells, the
      existence of a colocalization with TNF-alpha as well as with INF-gamma. All the
      cytokines studied were observed at an early stage of BALT development by
      immunohistochemistry and in bronchoalveolar cells (BAL cells) by flow cytometry
      and western blot. (1) The principal cytokine found at 4 days of age in BALT cells
      was TNF-alpha that increases along BALT development. The same behavior was found
      for cells containing IL-10 and INF-gamma. (2) TCR gammadelta+ cells colocalize
      mainly with TNF-alpha as it has been shown by immunohistochemistry in BALT and by
      flow cytometry when we studied BAL. The early appearance of TNF-alpha concomitant
      with TCR gammadelta+ cell suggests an important role for this cytokine along BALT
      development. Moreover, mutual regulation between them exists taking part in the
      immune surveillance and repair of damaged epithelia.

PMID- 15559372
TI  - Anti-laminin-1 autoantibodies, pregnancy loss and endometriosis.
AB  - Laminin-1 is a major component and multifunctional glycoprotein of basement
      membranes that consists of three different subunits, alpha1, beta1 and gamma11
      chains. It is the earliest synthesized network-forming protein during
      embryogenesis and plays an important role in embryonic development, embryonic
      implantation and placentation. We have recently shown that IgG anti-laminin-1
      antibodies were significantly associated with recurrent first-trimester
      miscarriages and with subsequent pregnancy outcome. Interestingly, these
      antibodies were also observed in patients with endometriosis-associated
      infertility but not in patients with other causes of infertility, including tubal
      factors, hormonal and uterine abnormalities. Laminin-alpha1, -beta1 and -gamma1
      mRNAs have been detected in 90% of endometriotic lesions and all laminin-alpha1, 
      beta1 and -gamma1 chains were localized in the basement membranes of glandular
      epithelium in endometriotic peritoneal lesions. Western blot analysis showed that
      anti-laminin-1 antibodies from those patients reacted with all laminin-1's
      chains. ELISA also confirmed that one of the target epitopes for these antibodies
      was located in a particular region of the laminin-1 molecule, i.e. the carboxyl
      terminal globular G domain of alpha1 chain. IgM monoclonal anti-laminin-1
      autoantibody, that we recently established, also recognized the G domain. Anti
      laminin-1 antibodies from mice immunized with "mouse" laminin-1, caused a higher
      fetal resorption rate with lower embryonic and placental weights. Thus, anti
      laminin-1 antibodies may be important in development of autoimmune-mediated
      reproductive failures and the assessment of the antibodies may provide a novel
      non-invasive diagnosis of endometriosis.

PMID- 15559373
TI  - The effects of Enterococcus faecium and selenium on methotrexate treatment in rat
      adjuvant-induced arthritis.
AB  - The effects of probiotic bacteria Enterococcus faecium (EF) and selenium were
      studied on methotrexate (MTX) treatment in rats with adjuvant arthritis (AA).
      Arthritic rats were preventive treated orally with the following substances:
      lyophilized EF (15mg/kg/day, 5 days a week); sodium selenite pentahydrate (SSe,
      0.050mg/kg containing 0.015 mg/kg selenium, 5 days a week); MTX (0.6 mg/kg/week),
      and their combinations for the period of 50 days from adjuvant application.
      Levels of serum albumin, serum nitrite/nitrate concentrations, hind paw swelling,
      arthrogram scores, whole body bone mineral density (BMD), and bone erosions were
      evaluated as markers of inflammation and destructive changes associated with
      arthritis. Long-term preventive treatment with low-dose MTX significantly
      inhibited the markers of both inflammation and arthritis. EF or SSe when
      administered singly or in combination had no significant effect on given
      parameters in arthritic rats. EF but not SSe potentiated the beneficial effects
      of MTX, which resulted in a more significant reduction of hind paw swelling,
      arthrogram scores and whole body BMD decrease. EF had a tendency to improve also
      the effect of MTX on serum albumin and nitrite/nitrate concentrations. Our
      results indicate that EF may increase the preventive effect of MTX treatment in
      rat AA by improving its anti-inflammatory and anti-arthritic effects.

PMID- 15559374
TI  - Determinants of vessel targeting in vasculitis.
AB  - Studies of autoimmune diseases have not yet elucidated why certain organs or
      vessels become the objects of injury while others are spared. This paper will
      explore the hypothesis that important differences exist in regions of the aorta
      that determine vulnerability to diseases, such as atherosclerosis, aortitis,
      giant cell arteritis and Takayasu's disease. The reader is invited to reassess;
      (1) whether the aorta is indeed a single homogeneous structure, and (2) whether
      the initial stage of aortitis (and indeed other diseases considered "autoimmune")
      may be primarily due to acquired alterations of substrate, that influence unique
      immune profiles, which by themselves may not be pathogenic. Disease
      susceptibility and patterns are influenced by many factors that are inborn and
      acquired. Examples include genetic background, gender, ethnicity, aging, prior
      and concomitant illnesses, habits, diet, toxin and environmental exposures.
      Studies of vascular diseases must assess how such variables may affect regional
      differences in endothelial cells, subendothelial matrix, vascular smooth muscle
      and the response of each to a variety of stimuli.

PMID- 15559375
TI  - The possible role of natural idiotopes in immune memory.
AB  - In this paper we report on the generation of Abs possessing specificities similar
      to those of Abs used in immunization, and on the generation of Id and anti-Id
      specificities in the sera of mice immunized with commensal bacterial antigens.
      The human monoclonal antibody IgM DJ (VH3/VL2) expresses natural antibody
      properties, natural idiotope (Y7), and specificity towards Lactic acid bacteria
      (LAB). When used in immunization it generates LAB-specific antibodies.
      Immunization with LAB, as detected in the presence of biotin-labelled mouse
      monoclonal anti-idiotopic antibodies Y7 and IgM DJ generates Abs1 and Abs2,
      respectively. These findings may imply that the recognition of bacterial motifs
      accords with the rules of idiotypic network theory. This theory, first proposed
      by Jerne in 1974 and often overlooked since, has been subject to change during
      the course of immunological research. Recent experiments concerning the
      recognition of bacterial motifs and natural memory in the immune system have
      inspired us in our attempt at explaining the possible role of natural Id in
      immune memory.

PMID- 15559376
TI  - Impaired IFN-gamma production by viral immunodominant peptide-specific tetramer+
      CD8+ T cells in HIV-1 infected patients is not secondary to HAART.
AB  - Studies on PBMC samples from HIV-1 infected patients have shown that despite
      substantial number of HIV specific CTLs, these patients gradually progress to
      AIDS. The present study was conducted to determine whether this paradox was
      secondary to the influence of protease inhibitors being utilized by these
      patients. Thus, aliquots of PBMC samples from 10 HIV infected humans with no
      prior history of anti-retroviral drug therapy (ART) and 6 HIV-infected patients
      that had been on HAART for > 1 year were analyzed for the frequency of HIV-1 Nef
      and Gag dominant peptide specific tetramer+ cells, respectively. The tetramer+
      PBMCs were analyzed for their ability to synthesize specific peptide induced IFN
      gamma utilizing both the ELISPOT and the intracellular cytokine (ICC) assays.
      Results of the studies showed that there was an overall correlation between the
      frequency of Nef and Gag peptide tetramer+ cells and the frequency of IFN-gamma
      synthesizing cells as assayed by either ICC or ELISPOT assay, markedly reduced
      values of IFN-gamma synthesizing cells per unit tetramer+ cells were noted in
      both group of patients. These data suggest that the frequency of HIV-specific
      CD8+ T cells is maintained during the chronic phase of infection, their ability
      to function is compromised and is not a reflection of ART. While the addition of
      IL-2, anti-CD40L and allogeneic cells led to partial increase in the ability of
      the tetramer+ cells to synthesize IFN-gamma, the addition of IL-4, IL-12, anti
      CD28 or a cocktail of antiTGF-beta, TNF-alpha and IL-10 failed to augment the IFN
      gamma response.

PMID- 15559377
TI  - Understanding autoimmune mechanisms in multiple sclerosis using gene expression
      microarrays: treatment effect and cytokine-related pathways.
AB  - Multiple sclerosis (MS) is a central nervous system disease in which activated
      autoreactive T-cells invade the blood brain barrier and initiate an inflammatory
      response that leads to myelin destruction and axonal loss. The etiology of MS, as
      well as the mechanisms associated with its unexpected onset, the unpredictable
      clinical course spanning decades, and the different rates of progression leading
      to disability over time, remains an enigma. We have applied gene expression
      microarrays technology in peripheral blood mononuclear cells (PBMC) to better
      understand MS pathogenesis and better target treatment approaches. A signature of
      535 genes were found to distinguish immunomodulatory treatment effects between 13
      treated and 13 untreated MS patients. In addition, the expression pattern of 1109
      gene transcripts that were previously reported to significantly differentiate
      between MS patients and healthy subjects were further analyzed to study the
      effect of cytokine-related pathways on disease pathogenesis. When relative gene
      expression for 26 MS patients was compared to 18 healthy controls, 30 genes
      related to various cytokine-associated pathways were identified. These genes
      belong to a variety of families such as interleukins, small inducible cytokine
      subfamily and tumor necrosis factor ligand and receptor. Further analysis
      disclosed seven cytokine-associated genes within the immunomodulatory treatment
      signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4)
      and FCAR (Fc fragment of IgA, CD89) that were common to both the MS gene
      expression signature and the immunomodulatory treatment gene expression
      signature. Our results indicate that cytokine-associated genes are involved in
      various pathogenic pathways in MS and also related to immunomodulatory treatment
      effects.

PMID- 15559378
TI  - Legal overprotection.

PMID- 15559379
TI  - The long and indecorous life of Tom Parr.

PMID- 15559380
TI  - Post-traumatic vertigo.
AB  - The vestibular-like symptoms that commonly follow head injury are most often due
      to one of a number of specific pathologies affecting vestibular, CNS or cervical
      structures. These pathologies can be readily identified in the majority of cases
      by appropriate testing in the examining room, and in vestibular function or
      neurodiagnosic laboratories. Whereas vestibular suppressants have a roll, they
      often delay recovery and have been supplanted as the mainstay of treatment in
      most cases by vestibular rehabilitation techniques. Given the large number of
      patients requiring outpatient management following head injury, it is appropriate
      that most generalists and many subspecialists should be aware of the differential
      diagnosis, workup and treatment options for post-traumatic vertigo.

PMID- 15559381
TI  - Self-implantable hearing devices.
AB  - Though traditional hearing aids remain the mainstay of treatment for most
      uncorrectable hearing loss, partially implantable devices may offer solutions
      when standard therapy fails.

PMID- 15559382
TI  - Laryngomalacia and its management: when to worry about the squeaky baby.

PMID- 15559383
TI  - Evaluation of the neck mass.
AB  - The differential diagnosis of a neck mass is extensive and varies with the age of
      the patient at presentation. A thorough work-up including an accurate history and
      complete head and neck examination often narrows the diagnostic possibilities.
      The fine needle aspiration biopsy has become an invaluable tool to aid clinicians
      in the evaluation of the neck mass and is safe, accurate, and cost-effective with
      minimal complications. The possibility of malignancy in any age group, especially
      in the late adult group, should never be overlooked. Close follow-up and
      aggressive pursuit of a diagnosis with appropriate work-up facilitates a timely
      and accurate treatment plan, which is essential to a favorable outcome.

PMID- 15559384
TI  - Update on influenza, 2004-2005.

PMID- 15559385
TI  - John Snow and the Broad Street pump: 150 years of epidemiology.

PMID- 15559386
TI  - Evidence of the effectiveness of endoscopic screening for colorectal cancer among
      residents of Rhode Island, 1988-2002.

PMID- 15559387
TI  - Words from the mouth.

PMID- 15559388
TI  - Liberalizing the ethical restrictions concerning romantic relationships between
      doctors and relatives of patients.

PMID- 15559389
TI  - Reminiscing on a life in medicine.

PMID- 15559390
TI  - Chronic hepatitis in Doberman pinschers. A review.
AB  - Chronic hepatitis in Doberman pinschers is predominantly seen in female dogs,
      usually between 4 and 7 years of age and was first recognized in the early
      eighties. The histopathological characteristics of Doberman hepatitis are those
      of micronodular cirrhosis with histological features of fibrosis, piece meal
      necrosis and progressive lymphocyte and plasma cell infiltration of the portal
      triads. Currently there are two hypotheses on the pathogenesis although neither
      of them has been elucidated. The first hypothesis is that of a copper toxicosis.
      The second is that of autoimmunity. Similarities and differences with other
      breeds and studies on both hypotheses are reviewed, as well as results of recent
      research of our group. Based on recent findings chronic hepatitis in Doberman
      pinschers is most likely to be a form of copper toxicosis. Although there are
      several indications that suggest autoimmunity as well, this still remains
      unclear.

PMID- 15559391
TI  - Hepatitis with special reference to dogs. A review on the pathogenesis and
      infectious etiologies, including unpublished results of recent own studies.
AB  - The causes of hepatitis in dogs are mostly unknown. Known causes of canine
      hepatitis are infectious (CAV-1), toxic (e.g. aflatoxin), and metabolic (copper
      accumulation). In order to understand the unknown causes, research in this field
      is necessary. Despite the marked progress in the knowledge on viral causes for
      human hepatitis, the involvement of infectious agents in the pathogenesis of
      hepatitis in the dog is still largely unknown. It is, like in human hepatitis,
      very likely that more than one causative infectious agent may cause hepatitis in
      the dog. This review presents the various forms of hepatitis in the dog, the
      known infectious and non-infectious causes of canine hepatitis, the infectious
      causes of hepatitis in man and other animals, and finally our recent infection
      and molecular studies to investigate possible infectious causes of canine
      hepatitis.

PMID- 15559392
TI  - [Retrospective evaluation of surgical versus conservative treatment of keratomas
      in 41 lame horses (1995-2001)].
AB  - A keratoma is a rather uncommon disorder of the equine hoof that can lead to
      lameness. Few quantitative data exist about the prognosis of different treatment
      regimens. The outcome of 41 cases that were presented to the Department of Equine
      Sciences in the period 1995-2001 and that were treated according to different
      regimens was retrospectively evaluated. All horses showed lameness that could be
      attributed to the keratoma: 23 (56%) were treated surgically using a standardized
      procedure, while the other 18 (44%) were treated conservatively. Results were
      based upon 35 horses; 6 were lost to follow-up. Range of recovery time for the
      surgically treated patients, was 2-12 months and for the conservatively treated
      group 2 weeks to 6 months. Of the surgically treated patients 83% (n =23)
      returned to the same or higher performance level as before the onset of the
      lameness, as opposed to 42% (n = 12) of the conservatively treated horses
      (p<0.05). The average hospitalization period was significanty longer for the
      surgically treated patients (35 vs. 5 days, p<0.05). It is concluded that
      surgical excision of the keratoma is the preferred treatment for horses suffering
      from lameness caused by a keratoma, because the better outcome outweighs the
      longer hospitalization and the longer overall recovery time.

PMID- 15559393
TI  - [Slaughter emergency].

PMID- 15559394
TI  - [Veterinarian, your advice is worth gold. Continued prevention of IBR and BVD].

PMID- 15559395
TI  - [Report of the 13th international symposium: lameness in ruminants].

PMID- 15559396
TI  - [Mammary gland health management in a broader view. Meeting mammary gland health
      panel].

PMID- 15559397
TI  - [Research to find new treatments for ferrets with adrenal gland tumors].

PMID- 15559398
TI  - [Veterinarians from earlier times].

PMID- 15559399
TI  - [Practice certification and recognition].

PMID- 15559400
TI  - [Recognized].

PMID- 15559401
TI  - [Motion BPL and member's opinion recognition and certification play a main role
      at the general meeting].

PMID- 15559402
TI  - [Report of the supervision committee].

PMID- 15559403
TI  - [Report of the symposium on avian influenza. 'Veterinarians bird free due to
      avian influenza?'].

PMID- 15559404
TI  - Let's talk about sex.

PMID- 15559405
TI  - [Illness due to work or to an overactive thyroid?].
AB  - An incapacity to work brought about by stress was diagnosed in two women aged 40
      and 38. They were both in conflict situations at work and had psychological
      problems. They stopped working but remained tired and irritable. After being
      unfit for work for more than a year they were diagnosed with hyperthyroidism
      which was treated appropriately. They both recovered and resumed work.
      Hyperthyroidism can impair physical and mental functioning. Presenting symptoms
      may be confusing, specifically if work-related factors appear to be the obvious
      implication. In The Netherlands, employees who become ill, consult their general
      practitioner or a medical specialist, who are concerned with diagnosis and
      treatment. They also report to their employer's occupational-health department,
      where the physician focuses on work-related factors that may impair health and on
      assessment of disability. Communication between all parties should be optimal.

PMID- 15559406
TI  - [Illness caused by work: a convincing clinical picture or chiefly a diminished
      feeling of well-being?].
AB  - Cooperation between occupational-health physicians and treating physicians can
      lead to a mutually convincing result. The input from the occupational-health
      physician consists of a careful and critical examination into the social and
      personal background of the employee on sick leave. The benefit of the doubt in
      the case of any remaining questions in the assessment of the degree of unfitness
      for work would then lean towards possibilities and not limitations. The degree of
      disability is then assessed by a convincing clinical picture and not by the
      diminished feeling of well-being of the patient.

PMID- 15559407
TI  - [Withdrawal of rofecoxib: a sign to be careful with coxibs in patients with
      increased cardiovascular risk].
AB  - Recently, the pharmaceutical company that manufactures rofecoxib (Vioxx) withdrew
      the drug on the basis of information indicating that it increases the number of
      acute myocardial infarctions and sudden cardiac deaths. Up until then, the
      advantages of selective cyclooxygenase-2 inhibitors (coxibs): notably fewer
      gastrointestinal complications than with the non-selective non-steroidal anti
      inflammatory drugs (NSAIDs) were considered to outweigh the adverse effects.
      Since the other coxibs share properties with rofecoxib, such as the potential for
      a higher thrombotic response in treated patients, it now seems wise to refrain
      from prescribing coxibs in patients with an increased cardiovascular risk profile
      until further data are available.

PMID- 15559408
TI  - [Still no proof of the efficacy of acupuncture in the prevention of migraine].
AB  - Besides pharmacological treatments for migraine, alternative non-pharmacological
      treatment strategies might be effective. In 2001, a Cochrane review concluded
      that acupuncture might be effective in migraine. The authors of a recent large
      trial also claimed that acupuncture might reduce the frequency of migraine
      attacks. However, this study failed to provide a clear answer due to serious
      methodological short-comings, for example with respect to randomisation and the
      clinical relevance of the main findings. In another recent, large, randomised
      controlled trial, the efficacy of acupuncture was not significantly different
      from that of the sham procedure. In conclusion, acupuncture is probably not
      effective in the prevention of migraine.

PMID- 15559409
TI  - [Prenatal investigations for Down's syndrome: medical-technical considerations
      and dilemmas arising from current screening methods].
AB  - Prenatal investigations can be divided into specific diagnostic investigations
      i.e. chorionic villus sampling, amniocentesis and selective ultrasonography for
      the detection of fetal abnormality, and screening tests which estimate the
      chances of the condition being present. These include routine ultrasonography and
      tests based on biochemical and echoscopic markers. Amniocentesis is the most
      reliable test to detect chromosomal anomalies, but is associated with a low risk
      of miscarriage and the results are known only relatively late in pregnancy.
      Implementing the prenatal screening tests will enable the better identification
      of those women with an increased risk of chromosomal anomalies, and consequently
      to fewer invasive diagnostic procedures. The choice whether to have prenatal
      screening should always be made by the parents after they have been told of the
      advantages and disadvantages of these investigations.

PMID- 15559410
TI  - [Tetanus prophylaxis in general practice].
AB  - In response to the report 'Immunisation against tetanus following injuries' from
      the Dutch Health Council, the Dutch College of General Practitioners, the
      National Coordinating Body for the Control of Infectious Diseases and The
      Netherlands Vaccine Institute have drawn up guidelines for tetanus prophylaxis in
      general practice. The number of situations in which the administration of tetanus
      immunoglobulin or tetanus vaccine is indicated is now considerably lower. Some of
      the unclear aspects of the report have been further worked out and translated
      into definite guidelines. The guidelines are not only useful for general
      practitioners but deserve to be followed by all doctors treating patients with
      injuries.

PMID- 15559411
TI  - [Diagnostic image (213). A pregnant woman with premature contractions and vaginal
      blood loss].
AB  - Emergency caesarean section was performed in a 40-year-old woman with solutio
      placentae. A Couvelaire uterus was diagnosed, showing typical blue-purple
      discolorations of the uterine wall, which are in fact haemorrhages caused by
      disseminated intravascular coagulation.

PMID- 15559412
TI  - [Impaired cognitive functioning in low-grade glioma patients: relationship to
      tumor localisation, radiotherapy and the use of anticonvulsants].
AB  - OBJECTIVE: To determine the effects of radiotherapy and other medical
      interventions on cognitive functioning in patients with a low-grade glioma (LGG).
      DESIGN: Cross-sectional study. METHOD: A total of 195 LGG patients, of whom 104
      had received radiotherapy 1-22 years previously, were compared to 100 patients
      with a low-grade haematological malignancy and 195 healthy controls. The analysis
      was aimed at differentiating between the effects of the tumour (disease duration,
      lateralisation) and treatment effects (neurosurgery, radiotherapy, use of
      anticonvulsants) on cognitive function and the relative risk of cognitive
      disability. RESULTS: LGG patients had lower performance levels in all cognitive
      domains than haematological patients and performed even worse when they were
      compared to healthy controls. Radiotherapy was associated with poorer cognitive
      functioning; however, cognitive disability was found only in patients receiving
      fractional doses exceeding 2 Gy. The use of anticonvulsants was strongly
      associated with disorders in the area of attention and planning functions.
      CONCLUSION: In this study, the tumour itself was the most damaging factor with
      respect to cognitive function and radiotherapy was associated with cognitive
      disability only if elevated fractional doses were used. Epilepsy or the use of
      anticonvulsants was also associated with diminished cognitive functioning.

PMID- 15559413
TI  - [Effective tracing of osteoporosis at a fracture and osteoporosis clinic in
      Groningen; an analysis of the first 100 patients].
AB  - OBJECTIVE: To analyse the results from a fracture and osteoporosis (FO)
      outpatient clinic in order to achieve efficient case-finding for osteoporosis in
      patients of 50 years and older with a fracture due to low-energy trauma. DESIGN:
      Descriptive. METHOD: Following the publication of new professional guidelines for
      case-finding and treatment of osteoporosis, an FO outpatient clinic was opened at
      the University Hospital of Groningen, The Netherlands, to which patients of 50
      years and older with a fracture due to low-energy trauma could be referred for
      further diagnosis and treatment after initial treatment for trauma. Bone-mineral
      density of the lumbar spine, hip and distal radius was assessed with dual-energy
      X-ray absorptiometry (DEXA). Patients with manifest osteoporosis, defined as
      having a fracture and a T-score < or = -2 SD at one of the measured sites, were
      put on medication. The results from the first 100 patients were analysed.
      RESULTS: In the first five months 74% (116/156) of the patients were seen in the
      FO clinic. In January 2004 the first 100 patients completed the diagnostic
      process. A total of 67 patients had manifest osteoporosis, 20 osteopenia and 13
      had normal bone density. Furthermore, 48% of the patients between 50 and 60 years
      old had manifest osteoporosis. Unrecognised vertebral fractures were found in 21
      patients. Forty-three percent of patients with manifest osteoporosis had low 25
      OH-vitamine D levels (< 30 nmol/l). Eleven patients were sent to the Department
      of Internal Medicine on indication of secondary osteoporosis. CONCLUSION: The FO
      outpatient clinic proved to be effective and useful for identifying and treating
      a population at risk of osteoporosis.

PMID- 15559414
TI  - [Deficiency of the fatty-acid oxidising enzyme medium-chain acyl-CoA
      dehydrogenase (MCAD) in an adult, detected during a neonatal screening
      programme].
AB  - In a trial running since October 2003 in the Dutch provinces of Friesland,
      Groningen, Drenthe and Overijssel neonatal screening for medium-chain acyl-CoA
      dehydrogenase (MCAD) deficiency has been added to the regular newborn screening
      programme for phenylketonuria, congenital hypothyroidism and adrenogenital
      syndrome. One of the questions to be answered by this trial is the cause of the
      strong variation in clinical expression of the disorder. Underdiagnosing is an
      important factor in this phenomenon, as shown by the data of a family of which
      the case histories of the two oldest children were discussed in this journal in
      1965. Both children died at a very young age. Recently, MCAD deficiency was
      diagnosed in the youngest child of this family, now a 34-year-old woman. This
      family history illustrates the variable clinical expression of MCAD deficiency,
      which can cause death but can also run a milder or even subclinical course.
      Moreover, this family history shows that the underdiagnosis of MCAD deficiency in
      deceased children may be a cause of the apparently limited clinical detection
      rate of this disease, for which a simple treatment consisting of life-style and
      dietary measures is available after diagnosis.

PMID- 15559415
TI  - [A fatal infection due to avian influenza-A (H7N7) virus and adjustment of the
      preventive measures].
AB  - In February 2003, the highly pathogenic avian influenza-A virus, subtype H7N7,
      was the causative agent of a large outbreak of fowl plague in the Netherlands.
      Two days after visiting a poultry farm that was infected by fowl plague, a 57
      year-old male veterinarian developed malaise, headache and fever. After 8 days he
      was admitted to hospital with signs of pneumonia. Five days later, his condition
      deteriorated alarmingly. Despite extensive pharmacotherapy he died 4 days later
      of acute pneumonia. Influenza-A virus, subtype H7N7, was identified by means of
      reverse transcriptase/PCR in broncho-alveolar washings that had been obtained
      earlier; routine virus culture yielded the isolate A/Nederland/219/03, which
      differs by 14 amino-acid substitutions from the first isolate in a chicken
      (A/kip/Nederland/1/03). Partly as a result of this case, the preventive measures
      were then adjusted; people who came into contact with infected poultry were given
      increased possibilities for vaccination and the administration of oseltamivir.

PMID- 15559416
TI  - [Diagnostic image (201). A man with a swelling of a finger].

PMID- 15559417
TI  - Lords debate illegal imports and biosecurity.

PMID- 15559418
TI  - How to be a vet and have a life.

PMID- 15559419
TI  - Developing the potential of the human-animal bond.

PMID- 15559420
TI  - Investigation of palpation as a method for determining the prevalence of keel and
      furculum damage in laying hens.
AB  - Old breaks of the keel and furculum were identified by palpation in 500 end-of
      lay hens from 10 flocks housed in free-range and barn systems, and the results
      were compared with the results obtained by a full dissection and inspection. The
      method was considered to be sufficiently precise to be used as a diagnostic tool
      although people using it would need to be trained. The results obtained by
      dissection indicated that 50 to 78 per cent of the birds in the flocks had breaks
      of the furculum and keel, but no other breaks of bones were detected.

PMID- 15559421
TI  - Detection of rabies viral antigens in non-autolysed and autolysed tissues by
      using an immunoperoxidase technique.
AB  - The objectives of this study were to determine the potential of an
      immunoperoxidase technique involving the avidin-biotin complex (ABC) stain for
      the diagnosis of rabies in fresh tissues and compare it with other standard
      methods, including the fluorescent antibody test (FAT), haematoxylin and eosin
      and Seller's stain, and to investigate its capacity to detect rabies antigen in
      autolysed tissues. Samples of non-autolysed brain from 81 domestic and wild
      animals suspected of having rabies were examined. Rabies antigen was detected by
      FAT in 41 of these samples and Negri bodies were detected in 40 (97.6 per cent)
      of them by the immunoperoxidase technique, in 25 by haematoxylin and eosin and in
      22 by Seller's stain. The sensitivity of the immunoperoxidase technique decreased
      as the tissues were left to autolyse; after two days it was 91.2 per cent, after
      four days 70.6 per cent, and after seven days 11.8 per cent.

PMID- 15559422
TI  - Management of leishmanial osteolytic lesions in a hypothyroid dog by partial
      tarsal arthrodesis.
AB  - A five-year-old male boxer, previously diagnosed with leishmaniasis and
      hypothyroidism, had gradually become unable to bear weight on its left hindlimb.
      Physical examination revealed a left popliteal lymphadenopathy, mild crepitus,
      and severe swelling of the left tarsal joint, a radiographic examination of which
      revealed severe bone destruction of the talus and a periosteal reaction of the
      calcaneus. Laboratory findings and serological tests suggested an active
      leishmanial infection, and a Leishmania species was identified by direct cytology
      of a sample from the osteolytic area and by indirect immunohistochemistry of a
      bone biopsy. The dog's condition improved when it was treated with meglumine
      antimonate and allopurinol. Because of the large osteolytic area and the
      increased use of the affected leg, a partial tarsal arthrodesis was performed to
      prevent a fracture. Five months after the surgery, the osteolytic area had healed
      completely and the calcaneus periosteal reaction had disappeared.

PMID- 15559423
TI  - Assessment of the risk of transmission of vaccine viruses by using insufficiently
      cleaned injection devices.

PMID- 15559424
TI  - Effects of pethidine and fentanyl on tear production in dogs.

PMID- 15559425
TI  - Identification and treatment of Dipetalonema grassii microfilariae in a cat from
      central Italy.

PMID- 15559426
TI  - Carpal bursitis associated with Brucella abortus in a horse in Nigeria.

PMID- 15559427
TI  - Outbreak of scabies in human beings, acquired from chamois (Rupicapra rupicapra).

PMID- 15559428
TI  - Standards for international trade.

PMID- 15559429
TI  - Antibodies to EBLV-1 in a domestic cat in Denmark.

PMID- 15559430
TI  - Regulation of paraprofessionals.

PMID- 15559431
TI  - Survey on the use of pain relief in cattle.

PMID- 15559432
TI  - [Image of the month. Incidentally discovered mediastinal mass].

PMID- 15559433
TI  - [Image of the month: "giant" inguinal-scrotal hernia].

PMID- 15559434
TI  - [How I treat ...scalp psoriasis].
AB  - Scalp involvement by psoriasis requires a ted treatment suited to the
      particularities of the anatomical site In course of time, the improvement of
      therapeutic agents and the galenic refinement have enhanced both the efficacy and
      cosmetic acceptability of the scalp care. The main therapeutic classes encompass
      keratolytics, dermocorticosteroids and vitamine D3 analogues. The patient
      compliance is reported to be best for the liquid or foam formulations.

PMID- 15559435
TI  - [Case report: congenital adrenal hyperplasia and ambiguous genitalia due to 3
      beta-hydroxysteroid dehydrogenase deficiency].
AB  - 3 beta-hydroxysteroid dehydrogenase deficiency is a disorder of steroid
      biosynthesis resulting in decreased production of all 3 groups of adrenal
      steroids. The symptomatology includes congenital adrenal hyperplasia disorders
      and ambiguous genitalia in 46, XY males. 3beta-HSD deficiency is a rare autosomal
      recessive genetic disorder. Much heterogeneity exists in the clinical
      presentation of this disorder.

PMID- 15559436
TI  - [Guidelines for the management of arterial hypertension in general practice].
AB  - Guidelines for the management of arterial hypertension are regularly updated.
      This article summarizes the last international guidelines in this field published
      last year. The decision to initiate an antihypertensive treatment will not only
      depend on blood pressure levels, but also on global cardiovascular risk
      assessment.

PMID- 15559437
TI  - [Echo Doppler post total hip arthroplasty: retrospective: study of 111 patients
      at CHBAH].
AB  - We studied all the patients who underwent a total hip arthroplasty during the
      last six months of 2001. They all had a postoperative venous Doppler echo
      (possibly repeated) followed by a phlebography in case of clinical doubt. They
      all received a prophylactic treatment by low molecular weight heparin. Our rate
      of deep venous thrombosis was 22% (from which 3% are) and of pulmonary emboli was
      2,7%. These figures are in keeping with those of large controlled studies. The
      risk factors identified are age and female gender. We discuss, based on the
      literature, the significance of lower deep venous thrombosis. We also discuss the
      best strategy to detect postoperative deep venous thrombosis in order to improve
      the cost/effectiveness ratio.

PMID- 15559438
TI  - [The different accesses to the left atrium].
AB  - The knowledge of the anatomy of the atria and interatrial septum permits
      different routes to approach the left atrioventricular valve. The Waterston's or
      Sondegaard's groove approach is the most frequently used, but other approaches
      such as Dubost'transseptal technique, vertical transseptal approach (Berreklouw
      Guiraudon), biatrial inferior transseptal approach (Couetil) or Saksena's
      approach may be relevant in special situations. It is the purpose of this article
      to review the anatomic and technical basis of these different approaches and
      their respective merits.

PMID- 15559439
TI  - [The Brugada syndrome].
AB  - The Brugada syndrome, a genetically transmitted disease according to an autosomal
      mode with a variable penetrance, is responsible for sudden death secondary to
      polymorphic ventricular tachycardia. The diagnosis is based on a typical
      electrocardiographical paturn that combines a right bundle branch block with ST
      elevation in the right precordial leads. In high risk patients, the automatic
      implantable defibrillator has the unique capability to protect against the
      occurrence of ventricular arrhythmias.

PMID- 15559440
TI  - [Non bullous impetigo: streptococcal or staphylococcal?].
AB  - Non bullous impetigo is very common among the pediatric population. It is caused
      by bacteria. For twenty years, Staphylococcus aureus has been the most frequently
      isolated organism (present in 80 % of non bullous impetigo lesions, it is the
      only pathogen cultured in 50 % of patients). The group A beta-haemolytic
      streptococcus is at the moment isolated alone in 3% of lesions and in association
      with S. Aureus in 30 % of patients. An epidemiologic change seems to have
      occurred. Until the early 1980s, group A beta-haemolytic streptococcus was indeed
      the most predominant etiologic agent causing non bullous impetigo. Unfortunately,
      the rate of resistance among staphylococci responsible of non bullous impetigo is
      increasing. As serious complications can follow this skin infection, an
      appropriate treatment is necessary combining local care, topical antibiotics and
      sometimes adjunction of systemic antibiotics.

PMID- 15559441
TI  - [Massive ovarian oedema].
AB  - Massive ovarian oedema is a rare tumor-like condition predominantly found in
      young women. It is considered malignant until otherwise proven because of its
      solid nature. The pre-operative diagnosis is very difficult. The frozen section
      examination can help for diagnosis and ensures conservative treatment with
      ovarian preservation. The authors report a case of a 23-years-old woman with
      right ovarian mass findings on ultrasound imaging. The diagnosis of massive
      ovarian oedema was made on frozen section after a right oophorectomy. Although
      most of reported cases has been handled by oophorectomy, the conservative
      treatment must be the ruler, especially since the disorder is benign and reaches
      the youth.

PMID- 15559442
TI  - [How I explore... Hair loss in cancer patients].
AB  - Increased hair loss followed, in some instances by an acute focal or total
      alopecia, can develop in some cancer patients. The surgical stress or procedure,
      radiotherapy and some chemotherapy regimens can be responsible for these
      disturbing events. The alopecia is transient or permanent according to its
      origin. Diverse diagnostic and prognostic methods are available for assessing
      alopecias. The trichogram is a rewarding one.

PMID- 15559443
TI  - [Spiriva].
AB  - SPIRIVA (tiotropium) is a long-acting anticholinergic bronchodilatator, inhaled
      once a day, which produces relaxation of airway smooth muscle through antagonism
      of acetylcholine at M3-muscarinic receptors. Its duration of action is at least
      24h with once daily administration of tiotropium. Several studies have shown its
      efficacy and its good tolerance in the treatment of patients who are suffering
      from moderate to very severe chronic obstructive pulmonary disease (COPD).
      SPIRIVA improves spirometric measurements and quality of life, and reduces
      dyspnea and exacerbation rate in COPD patients.

PMID- 15559444
TI  - [Effects of intensive insulin therapy after an acute myocardial infarction in
      patients with type 2 diabetes: results of the DIGAMI-2 trial].
AB  - The results of DIGAMI-2 (<<Diabetes Mellitus Insulin Glucose Infusion in Acute
      Myocardial Infarction>>) trial were presented at the 40th scientific congress of
      the European Association for the Study of Diabetes (EASD) in Munich on September
      6, 2004. The main objective of this multicentre international trial was to
      confirm the positive results of the first DIGAMI trial published in 1995--1997.
      This pilot trial demonstrated that insulin-glucose infusion followed by a
      subcutaneous multidose insulin regimen reduces total mortality after 1 and 3
      years in diabetic patients with acute myocardial infarction. DIGAMI-2, by
      comparing three groups of subjects receiving various interventions, aimed at
      determining the relative benefit resulting from the insulin-glucose infusion in
      the acute phase and that attributable to long-term intensive insulin therapy in a
      similar population of type 2 diabetic patients. No significant difference was
      observed between the three groups as far as total mortality and cardiovascular
      morbidity were concerned. These negative results may be explained by the absence
      of significant difference in blood glucose control between the three groups, by
      the fact that glycaemic targets were not reached in the intensive group and, last
      but not least, by a better management of other risk factors, allowing already
      markedly reduced cardiovascular morbidity and mortality in the reference group
      treated with conventional antidiabetic therapy. In conclusion, DIGAMI-2 argues
      for a multidisciplinary management of diabetic patients to reach strict glycaemic
      targets with an intensive insulin scheme and confirms the remarkable advances in
      cardiovascular protection thanks to an optimised global pharmacological approach
      combined with modern revascularisation procedures.

PMID- 15559445
TI  - The CEO's real legacy.
AB  - The literature on CEO succession planning is nearly unanimous in its advice:
      Begin early, look first inside your company for exceptional talent, see that
      candidates gain experience in all aspects of the business, and help them develop
      the skills they will need in the top job. It all makes sense and sounds pretty
      straightforward. Nevertheless, the list of CEOs who last no more than a few years
      on the job continues to grow. Implicit in many, if not all, of these
      unceremonious departures is the absence of an effective CEO succession plan. The
      problem is, most boards simply don't want to talk about CEO succession: Why rock
      the boat when things are going well? Why risk offending the current CEO?
      Meanwhile, most CEOs can't imagine that anyone could adequately replace them. In
      this article, Kenneth W. Freeman, the retired CEO of Quest Diagnostics, discusses
      his own recent handoff experience (Surya N. Mohapatra became chief executive in
      May 2004) and offers his approach to succession planning. He says it falls
      squarely on the incumbent CEO to put ego aside and initiate and actively manage
      the process of selecting and grooming a successor. Aggressive succession planning
      is one of the best ways for CEOs to ensure the long-term health of the company,
      he says. Plus, thinking early and often about a successor will likely improve the
      chief executive's performance during his tenure. Freeman advocates the textbook
      rules for succession planning but adds to that list a few more that apply
      specifically to the incumbent CEO: Insist that the board become engaged in
      succession planning, look for a successor who is different from you, and make the
      successor's success your own. After all, Freeman argues, the CEO's true legacy is
      determined by what happens after he leaves the corner office.

PMID- 15559446
TI  - Getting past yes: negotiating as if implementation mattered.
AB  - Many deals that look good on paper never materialize into value-creating
      endeavors. Often, the problem begins at the negotiating table. In fact, the very
      person everyone thinks is pivotal to a deal's success--the negotiator--is often
      the one who undermines it. That's because most negotiators have a deal maker mind
      set: They see the signed contract as the final destination rather than the start
      of a cooperative venture. What's worse, most companies reward negotiators on the
      basis of the number and size of the deals they're signing, giving them no
      incentive to change. The author asserts that organizations and negotiators must
      transition from a deal maker mentality--which involves squeezing your counterpart
      for everything you can get--to an implementation mind-set--which sets the stage
      for a healthy working relationship long after the ink has dried. Achieving an
      implementation mind-set demands five new approaches. First, start with the end in
      mind: Negotiation teams should carry out a "benefit of hindsight" exercise to
      imagine what sorts of problems they'll have encountered 12 months down the road.
      Second, help your counterpart prepare. Surprise confers advantage only because
      the other side has no time to think through all the implications of a proposal.
      If they agree to something they can't deliver, it will affect you both. Third,
      treat alignment as a shared responsibility. After all, if the other side's
      interests aren't aligned, it's your problem, too. Fourth, send one unified
      message. Negotiators should brief implementation teams on both sides together so
      everyone has the same information. And fifth, manage the negotiation like a
      business exercise: Combine disciplined negotiation preparation with post
      negotiation reviews. Above all, companies must remember that the best deals don't
      end at the negotiating table--they begin there.

PMID- 15559447
TI  - Bringing customers into the boardroom.
AB  - Misguided marketing strategies have destroyed more shareholder value than shoddy
      accounting or shady fiscal practices. Yet marketing functions typically reside
      deep in the organization, far from the executive suite and boardroom, and they
      are often poorly aligned with corporate strategy. Boards of directors, it would
      seem, have compelling reasons to monitor their companies' marketing activities.
      The authors argue that boards lack a clear understanding of how their companies
      are meeting customers' needs and how their marketing strategies drive (or often
      fail to drive) top-line growth. To help remedy that problem, they've devised a
      "marketing dashboard," a series of management reports that could give the board
      this critical knowledge. The dashboard has three parts, each of which the board
      should review regularly. The first part tracks the company's main business
      drivers--those business conditions that, when manipulated or otherwise changed,
      will directly and predictably affect the company's performance. The second part
      describes the specific innovations in a pipeline of growth ideas that will allow
      the company to reach its short- and long-term revenue goals. And the third part
      provides an overview of the company's marketing skill set so the board can
      determine not only if the company has enough marketing talent but also if it has
      the right marketing talent. Unlike isolated measures of marketing performance
      that are often insufficient, irrelevant, or misleading, the dashboard allows the
      board to quickly and routinely assess the effectiveness of its company's
      marketing strategies. Armed with a clear understanding of marketing's role and
      performance, the board can expose inadequate marketing campaigns, direct
      management to address the problem, and monitor progress.

PMID- 15559448
TI  - The Wild West of executive coaching.
AB  - Annual spending on executive coaching in the United States is estimated at 1
      billion dollars. Yet information about coaching's effectiveness is scarce and
      unreliable. No one has yet demonstrated conclusively what qualifies an executive
      coach or what makes one approach to executive coaching better than another.
      Barriers to entry are nonexistent--many executive coaches know little about
      business, and some know little about coaching. The coaching certifications
      offered by various self-appointed bodies are difficult to assess, and methods of
      measuring return on investment are questionable. But strategic coaching can
      provide critical help both to individuals and to organizations. In this article,
      Stratford Sherman, a senior vice president of Executive Coaching Network, and
      Alyssa Freas, the founder and CEO, explore the popularity of executive coaching
      and investigate ways to make the most of the experience. They argue that coaching
      is inevitably a triangular relationship between the client, the "coachee," and
      the coach. Its purpose is to produce behavioral change and growth in the coachee
      for the economic benefit of the client. The best way to maximize the likelihood
      of good results is to qualify all the people involved. Even so, many triangular
      relationships continue to generate conflict among all three parties. At the most
      basic level, coaches serve as suppliers of candor, providing leaders with the
      objective feedback they need to nourish their growth. Coaching gets executives to
      slow down, gain awareness, and notice the effects of their words and actions. On
      a larger scale, the best coaching fosters cultural change for the benefit of the
      entire organization. It provides a disciplined way for businesses to deepen
      relationships with their most valued employees while also increasing their
      effectiveness.

PMID- 15559449
TI  - Aligning incentives in supply chains.
AB  - Most companies don't worry about the behavior of their supply chain partners.
      Instead, they expect the supply chain to work efficiently without interference,
      as if guided by Adam Smith's famed invisible hand. In their study of more than 50
      supply networks, V.G. Narayanan and Ananth Raman found that companies often
      looked out for their own interests and ignored those of their network partners.
      Consequently, supply chains performed poorly. Those results aren't shocking when
      you consider that supply chains extend across several functions and many
      companies, each with its own priorities and goals. Yet all those functions and
      firms must pull in the same direction for a chain to deliver goods and services
      to consumers quickly and cost-effectively. According to the authors, a supply
      chain works well only if the risks, costs, and rewards of doing business are
      distributed fairly across the network. In fact, misaligned incentives are often
      the cause of excess inventory, stock-outs, incorrect forecasts, inadequate sales
      efforts, and even poor customer service. The fates of all supply chain partners
      are interlinked: If the firms work together to serve consumers, they will all
      win. However, they can do that only if incentives are aligned. Companies must
      acknowledge that the problem of incentive misalignment exists and then determine
      its root cause and align or redesign incentives. They can improve alignment by,
      for instance, adopting revenue-sharing contracts, using technology to track
      previously hidden information, or working with intermediaries to build trust
      among network partners. It's also important to periodically reassess incentives,
      because even top-performing networks find that changes in technology or business
      conditions alter the alignment of incentives.

PMID- 15559450
TI  - CRM done right.
AB  - Disappointed by the high costs and elusive benefits, early adopters of customer
      relationship management systems came, in the post dot-com era, to view the
      technology as just another overhyped IT investment whose initial promise would
      never be fulfilled. But this year, something unexpected is happening. System
      sales are rising, and executives are reporting satisfaction with their CRM
      investments. What's changed? A wide range of companies are successfully taking a
      pragmatic, disciplined approach to CRM. Rather than use it to transform entire
      businesses, they've directed their investments toward solving clearly defined
      problems within their customer relationship cycle. The authors have distilled the
      experiences of these CRM leaders into four questions that all companies should
      ask themselves as they launch their own CRM initiatives: Is the problem
      strategic? Is the system focused on the pain point? Do we need perfect data?
      What's the right way to expand an initial implementation? The questions reflect a
      new realism about when and how to deploy CRM to best advantage. Understanding
      that highly accurate and timely data are not required everywhere in their
      businesses, CRM leaders have tailored their real-time initiatives to those
      customer relationships that can be significantly enhanced by "perfect"
      information. Once they've succeeded with their first targeted CRM project, they
      can use it as a springboard for solving additional problems. CRM, in other words,
      is coming to resemble any other valuable management tool, and the keys to
      successful implementation are also becoming familiar: strong executive and
      business-unit leadership, careful strategic planning, clear performance measures,
      and a coordinated program that combines organizational and process changes with
      the application of new technology.

PMID- 15559451
TI  - Time-driven activity-based costing.
AB  - In the classroom, activity-based costing (ABC) looks like a great way to manage a
      company's limited resources. But executives who have tried to implement ABC in
      their organizations on any significant scale have often abandoned the attempt in
      the face of rising costs and employee irritation. They should try again, because
      a new approach sidesteps the difficulties associated with large-scale ABC
      implementation. In the revised model, managers estimate the resource demands
      imposed by each transaction, product, or customer, rather than relying on time
      consuming and costly employee surveys. This method is simpler since it requires,
      for each group of resources, estimates of only two parameters: how much it costs
      per time unit to supply resources to the business's activities (the total
      overhead expenditure of a department divided by the total number of minutes of
      employee time available) and how much time it takes to carry out one unit of each
      kind of activity (as estimated or observed by the manager). This approach also
      overcomes a serious technical problem associated with employee surveys: the fact
      that, when asked to estimate time spent on activities, employees invariably
      report percentages that add up to 100. Under the new system, managers take into
      account time that is idle or unused. Armed with the data, managers then construct
      time equations, a new feature that enables the model to reflect the complexity of
      real-world operations by showing how specific order, customer, and activity
      characteristics cause processing times to vary. This Tool Kit uses concrete
      examples to demonstrate how managers can obtain meaningful cost and profitability
      information, quickly and inexpensively. Rather than endlessly updating and
      maintaining ABC data,they can now spend their time addressing the deficiencies
      the model reveals: inefficient processes, unprofitable products and customers,
      and excess capacity.

PMID- 15559453
TI  - Access to oral healthcare: ethical, cultural competency, and diversity
      perspectives and the role of dental education.

PMID- 15559454
TI  - The true cost of a cavity. When a little hole becomes a 2,000 dollar money pit.

PMID- 15559455
TI  - Saving lives in the dental office.

PMID- 15559456
TI  - Preparing for the flu season.

PMID- 15559457
TI  - The ten most common all-ceramic preparation errors: a doctor/technician liaison's
      perspective.

PMID- 15559458
TI  - Improving visual communications in aesthetic and restorative dentistry: tips for
      successfully applying digital imaging in your practice.

PMID- 15559459
TI  - Know when to say "when" in endodontics: smoke on the water.
AB  - Ultimately, this article is a challenge to assess preoperatively both the patient
      and tooth and ask several important questions before a handpiece is ever picked
      up: (1) Can this tooth be restored? (2) Should this tooth be restored? (3) Does
      the patient want to save the tooth, and will the patient have the needed follow
      up treatment? (4) If this tooth cannot be restored as it is now, can it be made
      restorable through periodontal procedures? (5) If the tooth is restorable and the
      patient was my mother, am I the doctor to bring about the best long-term
      prognosis for the tooth endodontically? (6) Can this patient tolerate the
      contemplated treatment physically, mentally, emotionally, and financially? The
      long-term goal for the patient should be the maintenance of the tooth in
      asymptomatic function. In 30 years, like the Deep Purple rendition of Highway
      Star and Smoke on the Water, which had appeal to me in Seattle, someone will
      hopefully look at a given root canal and say that the treatment was originally
      performed well, for the right reasons, and stood the test of time.

PMID- 15559460
TI  - Using polyvinyl impressions for study models: a case report.

PMID- 15559461
TI  - The use of sectional matrix systems in class II direct composite restorations.

PMID- 15559462
TI  - Simplifying single-stage solid abutments: techniques for impressioning and
      temporization.

PMID- 15559463
TI  - A successful approach to the management of children: part 1.

PMID- 15559464
TI  - Labial bone concavity of the anterior mandible: a case report.

PMID- 15559465
TI  - Protecting electronic health information as part of HIPAA.

PMID- 15559466
TI  - Hand care and waterlines: update for the dental profession.
AB  - Two areas of the newly published CDC Guidelines for Infection Control in Dental
      Healthcare Settings-2003, hand hygiene and strategies for dental unit waterlines,
      are discussed in the context of a general strategy by which the oral healthcare
      provider can improve infection control in the patient care setting.

PMID- 15559467
TI  - Mastering computer scheduling: ensuring profitability while creating the perfect
      day.

PMID- 15559468
TI  - Developing a successful financial system.

PMID- 15559469
TI  - What is it like to be a patient in your office?

PMID- 15559470
TI  - Buyers' guide to all-ceramic systems.

PMID- 15559471
TI  - So, what's new in burs?

PMID- 15559472
TI  - In search of the holy grail and the golden fleece.

PMID- 15559473
TI  - If you can't beat them, join them (bimodal dialysis: the best of both worlds).

PMID- 15559474
TI  - Ultrafiltration failure in peritoneal dialysis patients.

PMID- 15559475
TI  - The complex economics of modality selection.

PMID- 15559476
TI  - End-stage renal disease and peritoneal dialysis in Bulgaria.

PMID- 15559477
TI  - Payment of USA physicians for dialysis care.

PMID- 15559478
TI  - Changes to the nephrology monthly capitation payments in the USA.

PMID- 15559479
TI  - Changes in dialysis reimbursement regulations in Germany.

PMID- 15559480
TI  - Peritoneal dialysis in the Far East: an awaking giant.

PMID- 15559481
TI  - Peritoneal dialysis in Ontario: a natural experiment in physician reimbursement
      methodology.
AB  - BACKGROUND: The factors that determine dialysis modality selection and
      distribution are not well understood. Physician reimbursement incentives have
      been suggested to play an important role. Under the fee-for-service system in
      Ontario that existed prior to July 1998, nephrologists were paid about sevenfold
      more for a hemodialysis (HD) patient than for a patient on peritoneal dialysis
      (PD). However, since then, nephrologists have been reimbursed via a modality
      independent capitation fee, whereby payment for any form of dialysis is the same.
      This was expected to markedly increase the use of PD. METHODS: When the
      capitation fee was introduced in 1998, a survey questionnaire of all Ontario
      nephrologists was done and repeated 3 years later (response rate 62.5%). Changes
      in dialysis modality incidence and prevalence rates in Ontario and in the rest of
      Canada were examined. RESULTS: On a scale of 1 to 7, nephrologists were convinced
      that the capitation fee was a good thing (mean rating 6.07); 75% said they had
      been seeing patients at every dialysis under the old system, compared to 41% now.
      Of significance, the proportion of prevalent patients on PD in Ontario declined
      from 27.3% in 1997 to 19.7% in 2000, increasing to 22.6% in 2002. Similarly, the
      incident PD rate seems to have stabilized, while the use of nonhospital-based HD
      has increased. CONCLUSIONS: Following the introduction of the capitation fee, PD
      use in Ontario continued to decline for 2 years, and then began to increase. In
      the rest of Canada, there are continuing declines in PD use. This is consistent
      with the hypothesis that the new incentives caused by the altered physician
      reimbursement are acting in a subtle way to increase PD and non-hospital-based
      HD. A longer period of observation may be required to assess the complete effect.

PMID- 15559482
TI  - Factors affecting the use of peritoneal dialysis among the ESRD population in
      India: a single-center study.
AB  - OBJECTIVES: Factors such as limited health-care budget allotment and poor
      accessibility of the majority of the population to hemodialysis (HD) facilities
      should favor the use of peritoneal dialysis (PD) in India. However, only 6% of
      end-stage renal disease patients undergoing dialysis in India are on PD. We
      undertook this prospective study to evaluate various factors that could
      contribute to this low rate of use of PD at a tertiary-care state-run hospital in
      Northern India. METHODS: All the patients who entered our HD or PD program from
      August 2001 to December 2003 were interviewed using a preset questionnaire. The
      questionnaire recorded their basic disease and comorbidity, social and
      demographic characteristics, awareness of the various modalities of renal
      replacement therapy (RRT), and the reasons for choosing their present modality of
      therapy. Treating nephrologists were also interviewed with respect to the factors
      that, in their opinion, were responsible for the limited use of PD at our
      institute. RESULTS: In total, 342 patients on HD, 66 patients on PD, and 24
      nephrologists were interviewed. The rate of PD use was 16.2%. Mean age of
      patients on HD and PD was 34.6 +/- 11.8 years and 62.9 +/- 10.3 years
      respectively (p < 0.0001). The incidence of diabetes mellitus and coronary artery
      disease in the HD and PD populations was 2.5% and 62.5%, and 9.1% and 46.7%
      respectively (p < 0.0001 for both). Only 30.4% of patients on HD were aware of PD
      as a modality of RRT and 83.6% of them found PD to be expensive, 65.4% had low
      enthusiasm toward a domiciliary therapy such as PD, and 61.5% were not
      recommended PD by their nephrologist. Only 5 (7.6%) patients were initiated on PD
      directly, the remaining 61 patients were shifted from HD after a mean duration on
      HD of 185.3 +/- 15.4 days: 67.1% were shifted due to poor tolerance of HD, 29.4%
      were advised to shift to PD because of comorbidity and vascular access problems,
      and only 3.3% took up PD because of the independent lifestyle it offered. None of
      the interviewed nephrologists routinely discussed PD in predialysis counseling.
      They found financial constraints (100%), lack of patient enthusiasm (100%),
      doubtful patient compliance (83.2%), and lack of an organized PD program (79.2%)
      to be the main factors limiting more widespread use of PD at our institute.
      CONCLUSIONS: Peritoneal dialysis is an underused modality of RRT at our
      institute. The patients who are taken up for PD at our institute are elderly and
      have a higher incidence of other comorbid conditions, such as diabetes mellitus
      and coronary artery disease. Also, most patients who switch to PD do so due to
      their unsuitability for HD rather than by their own choice. The factors
      contributing to this low rate of use of PD are ignorance of PD, increased cost of
      therapy, low enthusiasm toward domiciliary therapy, and lack of adequate
      infrastructure for PD at our institute. Effective predialysis counseling,
      reduction in the cost of the therapy, and development of an adequate
      infrastructure can increase the rate of use of PD.

PMID- 15559483
TI  - Enhanced ultrafiltration using 7.5% icodextrin/1.36% glucose combination
      dialysate: a pilot study.
AB  - OBJECTIVE: A pilot study to compare the use of a combination dialysate (7.5%
      icodextrin/1.36% glucose) versus icodextrin 7.5% alone for the long dwell in
      patients on peritoneal dialysis (PD). DESIGN: A 4-week, prospective, randomized
      crossover study. SETTING: A large regional renal unit providing treatment for a
      population of 1.7 million. PATIENTS: Five patients on continuous ambulatory PD
      (CAPD) and 3 patients on automated PD. MAIN OUTCOME MEASUREMENTS: Long-dwell and
      24-hour ultrafiltration volumes, body weight, 24-hour ambulatory blood pressure,
      and antihypertensive/diuretic tablet count. RESULTS: The use of the combination
      dialysate resulted in an increase in the median (interquartile range) long-dwell
      ultrafiltration, from 750 (650-828) mL to 1000 (889-1100) mL (p < 0.001), and 24
      hour ultrafiltration, from 739 (400-1623) mL to 956 (700-1750) mL (p < 0.001).
      Weight, blood pressure, and tablet count remained unchanged. CONCLUSIONS: The use
      of the novel combination dialysate resulted in a 33% increase in long-dwell
      ultrafiltration and a 29% increase in 24-hour ultrafiltration.

PMID- 15559484
TI  - Bimodal dialysis: an integrated approach to renal replacement therapy.
AB  - BACKGROUND: Peritoneal dialysis (PD) and hemodialysis (HD) are both widely used
      as sole therapies for end-stage renal disease (ESRD). There is still controversy
      over which (if either) is superior in terms of patient outcomes. Peritoneal
      dialysis offers the advantages of long, slow, continuous ultrafiltration and
      potentially enhanced protection of residual renal function (RRF). In contrast, HD
      offers superior solute removal at the cost of undesirable cardiovascular
      tolerance of high rates of sodium and water removal. The aim of this study was to
      investigate the clinical feasibility of offering a combined treatment of both
      modalities [bimodal dialysis (BMD)] to incident patients reaching ESRD. We set
      out to investigate if it might be possible to utilize the intrinsic advantages of
      both modalities within a setting of good patient acceptability. METHODS: We
      prospectively studied 8 patients. They were recruited in the pre-ESRD phase from
      a specialist low clearance clinic. An arteriovenous fistula was formed and
      peritoneal catheters were inserted. The BMD consisted of 2, 3-hour, high
      efficiency, euvolemic HD sessions per week in combination with 2 PD exchanges per
      day to provide a degree of solute clearance and all of the ultrafiltration.
      Adequacy was measured independently for each modality. Patients were followed
      using the standard range of evaluations in addition to RRF (by creatinine
      clearance and EDTA clearance), echocardiography (left ventricular mass and
      ventricular performance), treatment outcomes, patient symptoms, and
      complications. RESULTS: Mean time on BMD was 346 +/- 74.9 (range 245 - 431) days.
      Peritonitis rate was 21 months per episode (mean 0.6 +/- 0.9, 0 - 2 episodes per
      patient). Mean peritoneal ultrafiltration volume was 1.58 +/- 0.32 (1.3 - 2.1) L
      per day. Delivered Kt/V and weekly PD Kt/V did not change significantly.
      Patients' RRF was maintained over the study period, as were serum albumin and
      control of serum phosphorus. Blood pressure was controlled with a reduction in
      the number of antihypertensive agents. Left ventricular mass index reduced over
      the treatment period, from a mean of 194 +/- 31.2 (161 - 265) to 156 +/- 21.2
      (138 - 189) g/m2 (p = 0.05). Ventricular performance remained unchanged over the
      study [ejection fraction 50.4 +/- 11.1 (38 - 67) % to 48 +/- 8.0 (48 - 67) %].
      Mean time during BMD spent on HD alone was 4.2 +/- 6.9 (0 - 16) days, and on PD
      alone 9.2 +/- 10.6 (0 - 25) days. CONCLUSION: This study suggests that BMD is a
      feasible treatment for ESRD. It is associated with adequate solute removal and
      good hemodynamic/volume control, and allows increased treatment flexibility for
      coping with complications normally requiring recourse to unplanned HD with
      temporary central venous access.

PMID- 15559485
TI  - Determinants of peritoneal solute transport rates in newly started nondiabetic
      peritoneal dialysis patients.
AB  - OBJECTIVE: An overrepresentation of a fast peritoneal transport status in new
      peritoneal dialysis (PD) patients with extensive comorbidity has been reported in
      some studies. High mass transfer area coefficients (MTACs) of low MW solutes
      suggest the presence of a large effective peritoneal surface area. The mechanism
      is unknown. It might include comorbidity, chronic inflammation, or an effect of
      mesothelial cell mass on peritoneal transport by the production of vasoactive
      substances. To investigate their relative importance in early PD, peritoneal
      permeability characteristics in incident PD patients were analyzed for
      relationships with comorbidity, serum concentrations of inflammatory markers, and
      products of the mesothelial cells that can be detected in dialysate. DESIGN: A
      cross-sectional study. SETTING: A university hospital. METHODS: 46 patients who
      fulfilled the following inclusion criteria were analyzed: a standard peritoneal
      permeability analysis (SPA) within 6 months after the start of PD, no peritonitis
      prior to the SPA, older than 18 years, and without diabetes mellitus as a primary
      renal disease. The patients were divided into tertiles based on the MTAC
      creatinine: slow, medium, and fast transport groups. The Davies comorbidity score
      was used to assess comorbidity. Serum and dialysate samples obtained during the
      SPA were used to determine hyaluronan, interleukin (IL)-6, vascular endothelial
      growth factor (VEGF), and cancer antigen 125 (CA125). The dialysate
      concentrations of these substances were expressed as their dialysate appearance
      rates. RESULTS: No significant differences were present in the three transport
      groups for comorbidity, serum concentrations of inflammatory markers, or serum
      VEGF. Interleukin-6 and VEGF concentration attributed to local VEGF production
      were not different between the tertiles. Levels of VEGF were higher in the medium
      transport group compared to the slow transport group (p = 0.02); CA125 was higher
      in the fast transport group compared to the medium transport group (p= 0.01).
      When analyzed as continuous variables, MTAC creatinine was related to VEGF (r=
      0.33, p < 0.05) and CA125 (r= 0.41, p = 0.03). In linear regression analysis,
      VEGF influenced the association between CA125 and MTAC creatinine; IL-6 weakened
      this association only marginally. CONCLUSION: A fast peritoneal transport status
      in incident nondiabetic PD patients was not related to comorbidity. The
      relationships found between VEGF, CA125, and MTAC creatinine may suggest a role
      of VEGF in the regulation of the vascular peritoneal surface area, possibly
      already before structural abnormalities have developed. Our analyses are
      consistent with the hypothesis that mesothelial cell mass is an important
      determinant of the peritoneal transport status in incident nondiabetic PD
      patients without previous peritonitis. Of the many potential mediators produced
      by mesothelial cells, VEGF was more important than the inflammation marker IL-6.

PMID- 15559486
TI  - Analysis of the prevalence and causes of ultrafiltration failure during long-term
      peritoneal dialysis: a cross-sectional study.
AB  - BACKGROUND: Ultrafiltration failure (UFF) is a major complication of peritoneal
      dialysis (PD). It can occur at any stage of PD, but develops in time and is,
      therefore, especially important in long-term treatment. To investigate its
      prevalence and to identify possible causes, we performed a multicenter study in
      The Netherlands, where patients treated with PD for more than 4 years were
      studied using a peritoneal function test (standard peritoneal permeability
      analysis) with 3.86% glucose. UFF was defined as net UF < 400 mL after a 4-hour
      dwell. RESULTS: 55 patients unselected for the presence or absence of UFF were
      analyzed. Mean age was 48 years (range 18 - 74 years); duration of PD ranged from
      48 to 144 months (median 61 months); UFF was present in 20 patients (36%).
      Patients with and without UFF did not differ in age or duration of PD. Median
      values for patients with normal UF compared to patients with UFF were, for net UF
      659 mL versus 120 mL (p < 0.01), transcapillary UF rate 3.8 versus 2.1 mL/ minute
      (p < 0.01), effective lymphatic absorption 1.0 versus 1.6 mL/min (p < 0.05), mass
      transfer area coefficient (MTAC) for creatinine 9.0 versus 12.9 mL/min (p< 0.01),
      dialysate-to-plasma ratio (D/P) for creatinine 0.71 versus 0.86 (p < 0.01),
      glucose absorption 60% versus 73% (p < 0.01), maximum dip in D/P sodium (as a
      measure of free water transport) 0.109 versus 0.032 (p < 0.01), and osmotic
      conductance to glucose 3.0 versus 2.1 microL/min/mmHg (p < 0.05). As causes for
      UFF, high MTAC creatinine, defined as > 12.5 mL/min, or a glucose absorption >
      72%, both reflecting a large vascular surface, a lymphatic absorption rate (LAR)
      of > 2.14 mL/min, and a decreased dip in D/P sodium of < 0.046 were identified.
      Most patients had a combination of causes (12 patients), whereas there was only a
      decreased dip in D/P sodium in 3 patients, only high MTAC creatinine in 1
      patient, and only high LAR in 2 patients. We could not identify a cause in 2
      patients. Both groups had similar clearances of serum proteins and peritoneal
      restriction coefficients. However, dialysate cancer antigen 125 concentrations,
      reflecting mesothelial cell mass, were lower in the UFF patients (2.79 vs 5.38
      U/L). CONCLUSION: The prevalence of UFF is high in long-term PD. It is caused
      mainly by a large vascular surface area and by impaired channel-mediated water
      transport. In addition, these patients also had signs of a reduced mesothelial
      cell mass, indicating damage of the peritoneum on both vascular and mesothelial
      sites.

PMID- 15559487
TI  - Changes in water transport across the peritoneum during treatment with continuous
      ambulatory peritoneal dialysis in selected patients with and without peritonitis.
AB  - BACKGROUND: The natural course of longitudinal changes in peritoneal permeability
      and membrane area has been studied mostly by performing single-dwell studies in
      selected patients during treatment with peritoneal dialysis. PURPOSE: To evaluate
      the permeability characteristics of the peritoneal membrane by measuring drained
      ultrafiltration volume relative to initial glucose concentration in dialysis
      fluid from the start to the end of continuous ambulatory peritoneal dialysis
      (CAPD) treatment in a selected cohort of patients with and without peritonitis.
      DESIGN: A retrospective analysis of a group of patients whose peritoneal function
      was prospectively followed by recording drained ultrafiltration volume and
      glucose concentration in dialysis fluid for each dwell time, every day, during
      the time in CAPD treatment. Mean values from a 1-month period starting after the
      first 3 weeks of CAPD treatment were compared with the mean values from the last
      month of treatment. Approximately 11 500 exchanges were analyzed. Evaluations
      were done separately for short (day) and long (night) dwell times. PATIENTS AND
      STATISTICS: Of 132 patients commencing CAPD treatment in the time period selected
      for inclusion, 51 had enough data to be included in this study. Of these, 29
      patients experienced one or more episodes of successfully treated peritonitis.
      The selection of patients was not based upon patient characteristics, but upon
      criteria to satisfy predefined demands, such as number of measurements in each
      period, time since an episode of peritonitis, and time on CAPD treatment. Data
      were analyzed in three different groups: patients with episodes of peritonitis,
      patients without peritonitis, and both groups together. To assess changes between
      monthly mean at the start and at the end of CAPD, paired t-test was performed.
      Patients were also stratified into two groups according to low and high glucose
      in dialysis fluid at the start of CAPD (cutoff = 2 g/dL). Additionally, we used
      linear regression analyses to predict the level of drained ultrafiltration volume
      for a given level and change in glucose concentration. Mean treatment time for
      the entire group was 20 months (median 14.3 months), ranging from 6 to 69 months.
      RESULTS: No statistical differences in glucose concentrations were found between
      the periods compared. In the entire group there was an increase in
      ultrafiltration volume from the start to the end of CAPD treatment, for both day
      (p = 0.009) and night (p = 0.013) exchanges. Also, for patients without
      peritonitis, an increase appeared for day (p = 0.046) and night exchanges (p =
      0.053). However, for the cohort with peritonitis, only an insignificant increase
      was indicated. Patient characteristics, diabetic patients, the need for glucose
      in dialysis fluid when commencing CAPD treatment, the number of episodes of
      peritonitis, and time on CAPD did not influence the change in ultrafiltration.
      Regression analyses showed higher ultrafiltration response to a given level and
      change in glucose concentration at the end of CAPD treatment compared to the
      start values, also for the cohort with peritonitis. The regression coefficient
      between these variables was also significantly changed for both day (p < 0.0001)
      and night (p = 0.027) exchanges. CONCLUSION: A significant change in the
      regression coefficient between glucose in dialysis fluid and ultrafiltration
      volume reflects an increase in ultrafiltration response to a given level and
      change in glucose concentration during time on CAPD treatment. A parallel change
      after 5- and 9-hour dwells can be explained by a decrease in peritoneal surface
      area combined with a lesser decrease in peritoneal conductivity. However, changes
      in Starling forces across the peritoneal membrane are possible even in the
      absence of changes in peritoneal membrane characteristics.

PMID- 15559488
TI  - Alterations of paraoxonase and platelet-activating factor acetylhydrolase
      activities in patients on peritoneal dialysis.
AB  - OBJECTIVE: The more atherogenic lipid profile seen in peritoneal dialysis (PD)
      patients cannot fully explain the increased incidence of atherosclerosis in this
      population. Oxidative modification of low-density lipoproteins (LDL) is
      considered to play a central role in the atherogenic process, whereas high
      density lipoprotein (HDL) protects LDL from oxidation. On the other hand, it has
      been suggested that the LDL and HDL of PD patients are more resistant to
      oxidation than those of control subjects, while PD-HDL equally protects LDL from
      oxidation compared to control-HDL. Two HDL-associated enzymes have been shown to
      protect both LDL and HDL from oxidation: paraoxonase (PON1) and HDL-associated
      platelet-activating factor acetylhydrolase (HDL-PAF-AH). Furthermore, low PON1
      activity and high total plasma PAF-AH concentration, which represents mainly the
      LDL-associated enzyme, have been shown to be independent risk factors for
      coronary artery events in the general population. However, there are limited data
      regarding possible alterations of these enzymes in PD patients. The aim of our
      study was to examine the possible alterations of PON1 and PAF-AH activities in
      patients undergoing PD. DESIGN: A cross-sectional study. SETTING: A university
      medical center. PARTICIPANTS: 56 PD patients of Caucasian origin and 86 matched
      controls were studied. MEASUREMENTS: In all subjects, serum PON1 activity toward
      paraoxon (paraoxonase) and phenylacetate (arylesterase), as well as total serum
      and HDL-PAF-AH activities were measured; PON1 genetic polymorphisms known to
      influence PON1 activity (Q192R and M55L) were determined. RESULTS: The PD
      patients exhibited significantly increased serum PON1 (paraoxonase) and PON1
      (arylesterase) activities compared to controls, regardless of the PON1
      polymorphisms or the levels of HDL cholesterol. Additionally, PD patients had
      significantly elevated activities of total serum PAF-AH and HDL-PAF-AH,
      independently of the levels of LDL or HDL cholesterol. The ratio of HDL-PAF-AH/
      total PAF-AH, which has recently been suggested to be a potential marker of
      atherogenicity, was decreased in these patients compared to controls. Moreover,
      no difference in the prevalence of PON1 polymorphisms between PD patients and
      controls was found. CONCLUSION: The elevated activities of PON1 and HDL-PAF-AH
      could explain the increased resistance of PD-HDL to oxidation; the higher
      activity of total PAF-AH and the decreased HDL-PAF-AH/ total PAF-AH ratio could
      contribute to the increased incidence of atherosclerosis in these patients.

PMID- 15559489
TI  - Stability of drug additives in peritoneal dialysis solutions in a new container.
AB  - OBJECTIVE: To evaluate the stability of gentamicin, tobramycin, netilmycin,
      vancomycin, cefazolin, unfractionated heparin, and low molecular weight heparin
      when added to four different peritoneal dialysis (PD) solutions [Extraneal
      (Baxter Healthcare, Castlebar, Ireland); Physioneal, Nutrineal, and Dianeal
      (Baxter Healthcare, Grosotto, Italy)] in new, non-PVC Clear-Flex containers.
      MEASUREMENTS: Gentamicin, tobramycin, netilmycin, vancomycin, cefazolin,
      unfractionated heparin, and low molecular weight heparin were injected into
      separate bags of PD solution. Samples were withdrawn at predefined sampling times
      and the concentration of each drug was analyzed using high-performance liquid
      chromatography (for gentamicin, tobramycin, vancomycin, and cefazolin), or
      bioassay (for netilmycin, gentamicin, and tobramycin in Nutrineal), or
      coagulation methods (heparins). RESULTS: Netilmycin, vancomycin, cefazolin, and
      heparin in Physioneal, Nutrineal, Extraneal, and Dianeal were stable for at least
      24 hours at 25 degrees C and for an additional 4 hours at 37 degrees C.
      Gentamicin in Nutrineal, Extraneal, and Dianeal was stable for at least 24 hours
      at 25 degrees C and for an additional 4 hours at 37 degrees C; gentamicin in
      Physioneal was stable for less than 24 hours at 25 degrees C. Tobramycin in
      Nutrineal and Extraneal was stable for at least 24 hours at 25 degrees C and for
      an additional 4 hours at 37 degrees C; tobramycin in Physioneal and Dianeal was
      stable for less than 24 hours at 25 degrees C.

PMID- 15559490
TI  - Does secondary hyperparathyroidism play a primary role in causing peritoneal
      calcification in patients on CAPD?

PMID- 15559491
TI  - Acute systemic inflammation is associated with an increase in peritoneal solute
      transport rate in chronic peritoneal dialysis patients.
AB  - BACKGROUND: This study was performed to evaluate the effects of acute systemic
      inflammation on peritoneal solute transport rate (PSTR) in chronic peritoneal
      dialysis (CPD) patients. METHODS: A baseline standard peritoneal equilibration
      test (PET) was performed on each patient every 6 months, and blood concentration
      of high-sensitivity C-reactive protein (hs-CRP) was assayed every 2 months in our
      peritoneal dialysis clinic. Acute systemic inflammation was defined as a greater
      than 10-fold increase in hs-CRP concentration compared with baseline value, in
      the absence of peritonitis, and returning to baseline level in 2 months. In
      patients with acute systemic inflammation, PET and hs-CRP concentration assays
      were performed during inflammation and after recovery. Ten patients with acute
      systemic inflammation were enrolled in the inflammation group and 42 other
      patients served as controls. RESULTS: There were no significant changes in hs-CRP
      and dialysate-to-plasma ratio of creatinine (D/Pcreat) in the control group
      during the study period. In the inflammation group, median hs-CRP levels at
      baseline, during acute inflammation, and at recovery were 2.3 mg/L (range 0.3 -
      4.5 mg/L), 39.2 mg/L (range 15.1 - 117.4 mg/L), and 3.7 mg/L (range 0.9 - 8.9
      mg/L), respectively. Median D/Pcreat increased significantly from baseline (0.64;
      range 0.55 - 0.98) to time of acute inflammation (0.72; range 0.60 - 0.96) (p <
      0.05). The D/Pcreat at recovery was 0.67 (range 0.52 - 0.94), which decreased
      significantly from time of acute inflammation (p < 0.05). There was no
      correlation between changes in log (hs-CRP) and changes in D/Pcreat. CONCLUSION:
      We have shown here that acute systemic inflammation is associated with a
      temporary increase in PSTR in CPD patients.

PMID- 15559492
TI  - Fragmentation of polyurethane peritoneal dialysis catheter during explantation.

PMID- 15559493
TI  - Exit-site infection caused by Actinomyces odontolyticus in a CAPD patient.

PMID- 15559494
TI  - Reflections on an unsolved problem of biology: the evolution of senescence and
      death.
AB  - The evolutionary theory of senescence is based largely on principles first
      outlined by Williams in 1957, and consists of two relatively independent parts.
      The first part builds on ideas first put forward by Medawar, Haldane and others,
      to explain how something as negative as senescence could have been positively
      selected in evolution, particularly since most animals in the wild do not reach
      an age where senescence is expressed. Williams proposed that the genes
      responsible for the negative effects of senecence (senescence effector genes)
      were fixed in evolution by a process he called antagonistic pleiotropy, wherein a
      subset of genes selected because they confer a reproductive advantage early in
      life may have harmful effects in the post-reproductive period; negative selection
      against these harmful effects fails because, as pointed out by Medawar, the force
      of natural selection declines with age. The evolutionary history of senescence
      causing genes is seen as a nondirected accumulation of genes selected on a basis
      independent of senescence per se. In the second portion of his paper, Williams
      made a series of predictions about how the age of organisms at reproductive
      maturity, fecundity, lifespan and the timing of the onset of senescence would all
      interact in the life history of a species. These latter predictions, which do not
      depend at all on details of the mechanisms of selection of senescence effector
      genes, have been validated by numerous experiments over the past several decades.
      On the other hand, it has become increasingly evident that the senescence
      effector genes did not, as would be predicted by antagonistic pleiotropy,
      accumulate in a random, non-directed fashion in various species over evolutionary
      time. Rather, everything we know about these genes suggests they were present in
      eukaryotic founder cells shortly after, or even congruent with, the emergence of
      eukaryotes from their prokaryotic ancestors, and have been stringently conserved
      ever since. Complicated explanations of how so-called "death genes" may have
      evolved in eukaryotes are thus not required. It is suggested that the
      evolutionary theory of senescence should be focused on those evolutionary
      principles that have been validated experimentally, and that the notion of
      antagonistic pleiotropy--which cannot be experimentally validated--be dropped
      from our thinking about the evolution of senescence.

PMID- 15559495
TI  - [Arctic and southern freshwater pearl mussel Margaritifera margaritifera with
      long and short life span as a model system for testing longevity mechanisms].
AB  - The freshwater pearl mussel (Margaritifera margartifera) is one of the longest
      lived animals, attaining ages in excess of 150 years in polar climates. Because
      of its long life, the species may be useful for studying genetic and
      physiological mechanisms contributing to longevity. An ongoing study is comparing
      6 southern populations in Spain, with maximum recorded ages of 28-40 years, to 3
      Arctic populations in northwest Russia, with maximum ages of 114-190 years.
      Within Arctic populations, 40% of mussels live more than 100 years in rivers that
      are pristine. Possible evolutionary significance of northern longevity is an
      adaptation to severe cold and unstable environments in high gradient rivers.
      During winter, mussels have a near-famine existence during the Polar Night, and
      experience some shell damage from ice formation and flows. In summer, periodic
      droughts result in exposure and desiccation. In response to adversity, pearl
      mussels have acquired effective mechanisms for shell reparation and tissue
      healing and regeneration. Northern populations have low metabolic rates, reducing
      energy expenditure for growth under normal as well as extreme conditions.
      However, this species is capable of increasing metabolic rate for tissue
      regeneration and self-healing. The physiological adaptations to sustain longevity
      may provide useful clues to impedence of the aging process.

PMID- 15559496
TI  - [Senescence of biosystems of different levels].
AB  - The ability to senescence is absent in biosystems at early stages of their
      progressive evolution and appears at the late stages as a result of the growth of
      specialization elements of which biosystems consists. Biosystems of organism as
      well as superorganism and superspecies levels grow older. As a result of the
      ability to senescence is an increase of species diversity and improvement of the
      biogeochemical cycle on the Earth.

PMID- 15559497
TI  - [The premature ageing indices among professional drivers].
AB  - The studies of biological age, ageing rate, mental and physical work capacity in
      professional drivers were conducted. The examination revealed peculiarities of
      system organization of functions, which determine the mental and physical work
      capacity levels. Dynamics of the ageing process of professional driver's organism
      in relation with calendar age and driving experience were shown using the
      biological age model. The results point at the premature decrease of the mental
      work capacity in professional drivers. There was revealed premature contraction
      of the range of cardio-vascular system adaptive reactions on submaximum physical
      load in the drivers as compared with control group. It was proved, that premature
      age-related changes of physiologic and psychophysiologic indices in drivers are
      just "risk indicators", while long driving experience is a real risk factor,
      accelerating the ageing process. The "risk group" with manifestations of
      accelerating ageing was observed in 40-49-year old drivers with 15-19 years of
      professional experience. There was demonstrated the expediency of using the
      following methods for the age rate estimation according to biologic age indices
      and necessity of prophylactic measures for premature and accelerated ageing
      prevention among working population.

PMID- 15559498
TI  - [Research of influence of stress immobolization on relative mass of reproductive
      and immunocompetent organs of young and old rats].
AB  - Research of influence of stress immobilization on relative mass of reproductive
      and immunocompetent organs of young and old rats was carried out. The study of
      age features of correction by alpha-tocopherol of the peroxidation lipid (POL)
      stress deviations was realized. Specific answer of researched organs and age
      differences for stress effects was revealed. Tissue and age differences between a
      physiological level of POL at intact rats, and its change at stress animals
      fixed. Suppression of POL processes intensity against a background preliminary
      vitamin E injection and its combination with extreme effects specifies its
      protective action especially expressed in a liver. Results of researches show the
      large stress-resistance at young animals and the expressed damaging action of an
      stress at old animals.

PMID- 15559499
TI  - [Age-related peculiarities of effect of low dose ionizing radiation on blood
      antioxidant enzyme system status in Chernobyl's accident liquidation
      participant].
AB  - Age-dependency of activity of key blood antioxidant enzymes--superoxide dismutase
      (SOD), glutathione peroxidase and glutathione reductase has been estimated in 104
      men and women aged 25-60 years participated in the liquidation of the Chernobyl's
      accident since 6 years after irradiation. Control group includes 35 age-matched
      men and women. The results of study on 18 children aged 7-15 years and 5 children
      aged 2-6 years born by irradiated parents are given as well. Nineteen children
      were in the control group. Low-dose irradiation was found modify the pattern of
      age-related dependency of all enzymes studied. Most susceptible chain was enzymes
      of glutathione cycle both in liquidators and children. Study of late effects has
      shown that young people (<30 years) as well as children are most susceptible to
      low-level irradiation whereas most resistant were middle-aged people. This
      observation should be taken into consideration at selection of high-risk groups
      in an industry linked with chronic low-dose irradiation.

PMID- 15559500
TI  - [Peculiarities of somatic diseases in people of middle and old age survived
      Leningrad siege at childhood].
AB  - The results of a study on peculiarities of development of some diseases in adult
      peoples survived the Leningrad siege at childhood are presented. The age- and sex
      related differences in an incidence and clinical features of diseases are
      demonstrated. More frequent incidence of severe arterial hypertension, diabetes
      mellitus type 2, biliar calculite disease, chronic atrophic pangastritis,
      terminal stage of kidney failure, more early mortality, clinically unfavorable
      aortal atherosclerosis development, as well as atherosclerosis of coronary, brain
      and carotid artheria have been revealed. Specific histological and morphometric
      changes in kidney tissue of the patients at preclinical stage are demonstrated.

PMID- 15559501
TI  - ["Hypertensive heart" symptoms in the elderly].
AB  - Arterial hypertension is a leading pathology in the elderly. This pathology
      become extremely important in a spread atherosclerotic process commonly observed
      in the geriatric patients. While the aspects of left ventricle in arterial
      hypertensive patients are rather well known, this pathology needs further
      investigations connected with the studies on age-related changes in
      cardiovascular system. Particular attention should be paid to a symptomatic of
      "hypertensive heart" in the elderly patients.

PMID- 15559502
TI  - [Clinicotherapeutic aspects of neurosis-like states in elderly patients with a
      psychoorganic syndrome of vascular genesis].
AB  - The neurosis-like manifestations take up an important place in the clinical
      symptomatology of elderly patients with a psychoorganic syndrome of vascular
      genesis. The objective of this study consisted in identifying the predictors of
      the therapy effectiveness for similar patients. 109 patients with the mean age
      equal to 68.3+/-1.4 years were evaluated. The complex therapy included correctors
      of the cerebral blood circulation, neurometabolic stimulators, psychotropic drugs
      as well as psychocorrective interventions. It was found that in neurosis-like
      states with predominance of anxiety, the peculiarities of patients'
      psychoemotional life conditions exert the greatest influence on the effectiveness
      of treatment. And in case of asthenic manifestations' leading position in the
      symptomatology of the above-mentioned states, in the foreground within this
      context the predictors connected with the intensity of cerebroorganic changes
      proper are situated. Modern antidepressants as well as their combinations with
      neuroleptics, which possess a "soft" effect, and nootropic drugs, have occupied a
      principal place in the effective pharmacotherapy of neurosis-like manifestations.

PMID- 15559503
TI  - [New methods of urinary bladder cancer detection at the early stage of the
      disease in patients of various ages].
AB  - In the sickness rate's structure of the malignant neoplasms the urological
      localization take 6.8 per cent (%). Among them 70% is cancer of the urinary
      organs. The average age of the patients with cancer of the urinary bladder is
      from 65.2 to 69.7 years old. The use of fluorescent cystoscopy allows to improve
      the quality of the diagnostics of the urinary bladder's mucous' neoplastic
      changes. It is illustrated that the fluorescent cystoscopy's sensitivity is 96.9
      98.7% and exeeds the sensitivity of simple cystoscopy research method for more
      than 20%. Carcinoma in situ was found 2 times more often than with the help of
      traditional cystoscopy and "blind" biopsy. Carrying out urinary bladder's wall
      transuretral resection under the photodynamic control increases the radical
      character of the endoscopic operation and allows to reduce the quantity of
      cancer's relapses by decreasing the amount of residual tumors. The test
      examination (in a year after the operation) has shown that the tumor's
      recurrences were registered 2.2 times more seldom in those group of patients,
      which had the neoplasms extracted under the photodynamic control.

PMID- 15559504
TI  - [Immunomodulators and cytokines in the treatment of internal diseases, associated
      with immunologic status disturbance in elderly patients].
AB  - The last years witnessed significant change in therapeutic and infectious
      pathology of man, its immunoreactivity changed, especially in elderly patients.
      Thus, older people show the increase of chronic infectious-inflammatory diseases,
      characterized by flaccid, constantly recurring course, torpid to adequate
      etiotopic therapy. They are caused by conventionally-pathogenic or opportunistic
      microbes, often with atypical biological properties, having multiple resistance
      to antibiotics. About 30 new pathogenic microorganisms were revealed for the last
      20-30 years, including HIV-infection agent. The number of patients with allergic
      and autoimmune diseases increased, thus resulting in high urgency of this problem
      in gerontology. Decrease of immunologic reactivity, observed practically in all
      parts of the world, but mostly manifested in Russia, is one of the causes of
      infectious pathology, including pathology of inner organs, manifestation of
      allergic and autoimmune diseases. General practitioners, gerontologists
      understand that to cope with the increased rate of infectious, allergic or
      autoimmune diseases only by antibiotics or anti-inflammatory medicines is next to
      impossible. It's clear now that the use of only chemotherapeutic drugs in
      treatment of elderly and therapeutic patients is a mistake. Immunocorrective
      medicines, which stimulate reparative processes, allow to accelerate the
      processes of involution and shorten the general period of treatment. Antibiotic
      inhibits the agent multiplication, but its complete elimination from the body is
      a result of immune factors activity. In elderly patients with inner organ
      pathology and chronic pathology on the background of the suppressed
      immunoreactivity the effect of antibiotics, as well as antifungal, antiviral and
      other chemotherapeutic medicines is ineffective or of low effect. Optimal
      clinical effect in elderly patients can obviously be achieved only if there is
      synergism in the activity of the body protective forces and antimicrobial drugs.
      Thus, immunoreactivity dysfunction has a significant part in the pathogenesis of
      inner organ diseases in elderly patients with the disturbance of immunological
      status. So in complex of medical means, indicated for this pathology, adequate
      immunotherapy plays a special role, and the main problem is the choice of
      particular drugs.

PMID- 15559505
TI  - [The role of partial myocardial revascularization in treatment of elderly
      patients with ischemic heart disease].
AB  - One of the main difficulties in cardiology is how to correctly choose the volume
      and method of treatment in elderly patients with ischemic heart disease. 165
      elderly patients with IHD were included into the study. 83 patients received
      partial myocardial revascularization by PTCA and stenting and 82 patients were on
      the conservative medical treatment. The state of coronary flow was estimated by
      means of the Holter-monitoring and treadmill-test results. Contraction ability of
      the heart was evaluated by echocardiography. The Quality of life level in
      patients was measured by SF-36 questionnaire. The results prove that elderly
      patients with IHD can benefit from the early partial myocardial revascularization
      which increases coronary circulation, quality of life level and preserves left
      ventricular function.

PMID- 15559506
TI  - [The age aspect of treatment of patient with ulcer of gastroduodenal zone].
AB  - The existent methods of treatment patient with ulcer of gastroduodenal zone
      provide treatment of ills in correspondence with "Standards..." and don't take
      into account age features of patient. For increase efficiency of treatment
      patient with gastric ulcer taking into account infection Helicobacter pylori, age
      features a patient, we conduct the treatment 612 ills using eradication therapy,
      laser therapy, needlereflexotherapy. We made deduction that eradicates
      Helicobacter pylori increases time of remission of disease. The
      needlereflexotherapy conducting with using our methods measures spud of
      cicatrisation gastric ulcer, especially in cases with the elderly ills. The laser
      therapy conducting with using our methods especially increases speed of
      cicatrisation gastric ulcer in cases with the elderly ills, too.

PMID- 15559507
TI  - [Possibilites to improve the cerebral venous tonus in patients suffering of
      accelerated ageing in blood circulation system by the nonmedicamentousal
      sympathocorrection method].
AB  - The aim of the study was to evaluate the effectiveness of the transdermal electro
      impulses directed on ganglions stellatum in order to prevent the accelerated
      ageing and improve the cerebral venous flow. Using by the angioscanning method it
      was been found the phenomenon of ectasia in venae jugularis int. in patients
      suffering of accelerated ageing in 100% cases. The normalization of venous
      diameter after the treatment by electrical impulses has been found in 31-55% of
      cases.

PMID- 15559508
TI  - [The influence of substances revealing geroprotective of spontaneous
      carcinogenesis in mice].
AB  - The review presents the results of experimental studies conducted by the author.
      CBA, SHR, HER-2/neu and SAM mice revealed inhibition of age-related alterations
      in estrus function and spontaneous tumour development and showed life span
      extension under the influence of the pineal gland hormone Melatonin, synthetic
      peptide bioregulator Epitalon, delta-sleep-inducing peptide Deltaran,
      enterosorbent Aqualen and succinic acid containing preparation Neuronol (Noogam).
      The observed effect depended on the dose and conditions of administration, as
      well as genetic predisposition of the particular mice strains to tumour
      development.

PMID- 15559509
TI  - [Almost like in real life: physicians' health in the film M.D. from Hollywood].

PMID- 15559510
TI  - [Unclear gastrointestinal complaints. When is the diet change the right
      treatment?].

PMID- 15559511
TI  - [Where are the Federal League professionals especially sensitive. Pubic bone
      inflammation: the crux of the kicker].

PMID- 15559512
TI  - [Autopsy study unveils flaws in the diagnosis. Systemic mycoses are often
      diagnosed post mortem].

PMID- 15559513
TI  - [Endurance sport or muscle strengthening. Daily 45 minutes' training alleviates
      arthritis pain].

PMID- 15559514
TI  - [Deficient communication with cancer patients].

PMID- 15559515
TI  - [Scientists can laugh, too. This year's unreliable Nobel Prizes].

PMID- 15559516
TI  - [Protein, erythrocytes or leukocytes in the urine. What further diagnostic steps
      are indicated?].

PMID- 15559517
TI  - [Hematuria and nephritic sediment].
AB  - Vigorous physical exercise is just as likely to be the cause of hematuria as are
      diseases of the efferent urinary tract, inflammatory renal disease or tumors. The
      microscopic search for dysmorphic erythrocytes (acanthocytes), casts or
      leukocytes in the sediment is a helpful technique for deciding the how to proceed
      with further diagnostic measures. Morphological changes in more than 17% of the
      erythrocytes are highly suggestive of a glomerular cause, Also, the presence of
      various casts points to kidney disease. The typical microscopic picture of
      interstitial nephritis is sterile leukocytosis. This may be of atheroembolic
      origin, medication-induced, or viral. In any case, the nephritic sediment should
      be clinically evaluated only in the context of further information such as the
      patient's age, comorbidities, or medication.

PMID- 15559518
TI  - [Urine diagnosis and leukocyturia].
AB  - The most common cause of leukocyturia is--in conjunction with bacteriuria--an
      infection of the urinary tract. In the sediment, leukocytes may be differentiated
      into neutrophil or eosinophil granulocytes or lymphocytes. When contamination has
      been excluded, leukocyturia in the absence of significant bacteriuria mandates a
      further diagnostic evaluation. Of necessity for an accurate diagnostic work-up
      are appropriate urine sampling, rapid examination of the samples obtained, and
      standardized examination conditions.

PMID- 15559519
TI  - [Differential diagnosis of proteinuria].
AB  - Normally, protein secretion in the urine is less than 150 mg/day or less than 100
      mg/g creatinine. Orthostatic proteinuria, proteinuria in the presence of fever,
      and effort proteinuria are benign forms. In cases of persistent proteinuria,
      prerenal or overflow proteinuria are distinguished from renal and post-renal
      proteinuria. Renal forms can be differentiated into glomerular and tubular as
      well as mixed forms. The urine dipstick is of only low sensitivity, and is
      therefore unsuitable as a screening test for diabetic microalbuminuria. In
      addition, it cannot detect immunoglobulin light chains in Bence Jones
      proteinuria. For the differentiation between glomerular and tubular forms of
      proteinuria, the determination of marker proteins in the urine, for example,
      alpha1 microglobulin, albumin and IgG, has proven utility.

PMID- 15559520
TI  - [Diabetic coma and hypoglycemia in children. What to do when in an emergency].
AB  - With a few very rare exceptions, hypoglycemia and diabetic coma almost always
      occur in patients with diabetes mellitus, and are among the most common
      emergencies in children. For the emergency physician, it is important, on the
      basis of a specific history-taking and information from, for example, family
      members, supplemented by a clinical examination done in the light of knowledge of
      the typical symptoms of each of the entities, to determine whether hypoglycemia
      or diabetic coma is presenting. The most important technical examination is the
      measurement of blood glucose. In the event of hypoglycemia, the first therapeutic
      measure is the administration of sugar--in the case of a comatose patient via a
      venous line. The s.c. or i.m. administration of glucagon to achieve short-term
      improvement might be considered. In the event of a diabetic coma, abundant
      electrolyte solution is initially needed, followed by i.v. insulin. Referral to
      hospital is mandatory.

PMID- 15559521
TI  - [False and hazardous prescriptions from 20 family practices. The most frequent
      errors of the colleagues].

PMID- 15559522
TI  - [Time points in the new EBM. Do family physicians get faster to the check mill?].

PMID- 15559523
TI  - [Fewer points but more use of time. How long does your fee take?].

PMID- 15559524
TI  - [Therapy of heart failure after myocardial infarction. With eplerenone a new
      course].

PMID- 15559525
TI  - [More benefit in hypertension and high-grade reduction of the pump performance.
      Earlier beginning of therapy maximizes the benefit].

PMID- 15559526
TI  - [Slime fight in the lay media. Were the Vioxx fatal cases kept secret?].

PMID- 15559527
TI  - [10-minute consultation. Incidentaloma of the hypophysis].

PMID- 15559528
TI  - [Look diagnosis."Doctor, my uvula is double"].

PMID- 15559529
TI  - [Diagnosis of paraneoplastic neurological syndromes].
AB  - INTRODUCTION: Paraneoplastic neurological syndromes are rare non-metastatic
      manifestations of malignancy. They are differentiated from side effects of tumor
      therapy, tumor-associated coagulopathy, infections, metabolic, and nutritional
      disorders. In the majority of cases neurological symptoms precede diagnosis of
      associated malignancy. Detection of anti-neuronal antibodies suggests a
      paraneoplastic mechanism. OBJECTIVES: To summarize syndromes, diagnostic steps,
      and currently available diagnostic possibilities. METHODS AND RESULTS: Serum
      and/or cerebrospinal fluid is analysed using indirect immunfluorescence and
      Western blotting. The pattern of immunoreactivity suggests the type of antibody.
      Anti-Hu antibody immunolabels predominantly nuclei, and less the cytoplasm of
      central and peripheral nervous system neurons. Anti-Yo shows cytoplasmic
      immunoreactivity primarily of cerebellar Purkinje cells, while anti-Ri is
      somewhat similar to anti-Hu except that peripheral nervous tissue lacks
      immunoreactivity. Examination of non-neural tissue allows exclusion of nuclear
      immunostaining caused by other antinuclear antibodies. Western blot examination
      specifies the anti-neuronal antibody. CONCLUSIONS: 1. Paraneoplastic neurological
      syndromes may occur without defined malignancy. 2. Clinical diagnosis is
      supported by immunofluorescent/Western blot/ELISA detection of antibodies. 3.
      Knowledge of antibody may suggest the origin of malignancy. 4. Tumor and
      immunomodulatory therapy may be considered, however, prognosis is different in
      distinct tumors and syndromes.

PMID- 15559530
TI  - [Eradication of Helicobacter pylori infection in Europe: a meta-analysis based on
      congress abstracts, 1997-2002].
AB  - BACKGROUND: Meta-analyses evaluated several aspects of Helicobacter pylori
      eradication based on the randomised controlled trials. AIM: to perform a meta
      analysis of the papers presented at the European Helicobacter Pylori Study Group
      and United European Gastroenterology Week meetings from 1997 to 2002. METHODS:
      Abstracts dealing with the eradication of Helicobacter pylori have been reviewed
      and the randomised, controlled studies from European countries were included. The
      studies were classified into groups based on eradication schedules, antibiotics
      used and country of provenience. The pooled eradication rates were calculated and
      the differences were assessed by multiple variance analysis. RESULTS: One-hundred
      and two studies were accepted comprising 25,644 cases and 398 treatment arms. The
      eradication rate of proton pump inhibitor-based first line triple therapies was
      80.4% (confidence interval: 78.9-81.8); no difference was observed between the
      five proton pump inhibitors (p > 0.05). Ranitidine bismuth citrate based regimens
      were efficient in 79.9% (75.7-84.0) (p = 0.95 vs PPI). H2 blockers-based
      therapies achieved 68.6% (59.0-78.1) (p = 0.0007 vs proton pump inhibitor and p =
      0.005 vs ranitidine bismuth citrate-based regimens). Proton pump inhibitor-based
      double combinations were efficient in 47.1 (31.9-62.4) (p = 0.001 vs triple
      regimens). Clarithromycin+amoxicillin/nitroimidazole combinations achieved rates
      of 79.6% and 84.1%, respectively, while amoxicillin-nitroimidazole regimens were
      less efficient (72.5%, 66.6-78.5) (p = 0.006). The pooled eradication rate of
      second-line triple regimens was 75.5% (69.9-86.4)(p = 0.08 vs primary treatment).
      Quadruple therapies were successful in 81.1% (76.6-85.6) of cases as first-line
      and 73.8% (61.2-86.4) as second-line regimens (p = 0.77 and p = 0.02 vs triple
      regimens). The pooled eradication rates varied from 58% to 92% in the European
      countries. CONCLUSIONS: The pooled eradication rate of the primary proton pump
      inhibitor/ranitidine bismuth citrate-based triple regimens are comparable with
      the results of meta-analyses. H2 blocker-based triple and proton pump inhibitor
      based double regimens are of lower efficacy. Quadruple regimens were not better
      than triple therapies. The eradication rates per country varied, approaching 80%
      in most places. The results confirm in part post-hoc the validity of the
      Maastricht consensus recommendations.

PMID- 15559531
TI  - [The relationship between benign liver tumors and free radicals].
AB  - The purpose of this review was to summarise what is known about the benign
      hepatic tumors, especially the role that free radicals play in the etiology and
      in the complications of these neoplasms. Nowadays benign liver tumors are
      considered as common entities. With the technical developments of radiology their
      diagnosis has become much easier, but still it is the major difficulty for the
      doctor to handle. There are different types of benign hepatic neoplasms: liver
      cyst, hemangioma, hepatocellular adenoma, focal nodular hyperplasia and there are
      also some rare tumor types. The relationship between hepatocellular adenoma and
      the use of oral contraceptives is well known. The oral contraceptives reduce the
      antioxidant capacity of the blood, this could be an explanation for the
      generation of these neoplasms. Benign liver tumors are also associated to
      thrombotic reactions. These neoplasms may require surgical treatment, so the
      oxidative stress is one of the main prognostic factors of the patients' survival.

PMID- 15559532
TI  - [Identification of congenital adrenal hyperplasia by measurement of blood-spot 17
      hydroxyprogesterone].
AB  - Identification of congenital adrenal hyperplasia by measurement of blood-spot 17
      hydroxyprogesterone. INTRODUCTION: 21-hydroxylase deficiency (21-OHD) is the most
      common cause of congenital adrenal hyperplasia (CAH). The simplest way to
      diagnose the disease is the measurement of 17-hydroxyprogesterone level in the
      serum. AIMS: The aim of the study was to analyze the clinical advantages of a
      centralized diagnostic strategy in Hungary using measurement of 17
      hydroxyprogesterone in dried blood spots. METHODS: During a 20 years period blood
      spot samples of 1837 patients suspected to have CAH have been investigated.
      RESULTS: 185 patients proved to have CAH (classic 21-OHD 155; NCAH 27; 11beta-OHD
      3 patients). A national database for CAH was set up by collecting further
      information about CAH patients in the country. Based on the frequency of the
      disease in girls during the nineties, the incidence of classical 21-OHD was
      calculated to be 1:11,147 in Hungary. CONCLUSIONS: Early diagnosis, optimal
      medical and surgical treatment, and attention to compliance may lead to further
      decrease in morbidity and mortality of CAH patients.

PMID- 15559533
TI  - [One man's poison is another man's remedy. From arrowpoison to musclerelaxation].

PMID- 15559534
TI  - [Contributions to the work of Gyula Kerkovits].

PMID- 15559535
TI  - [Lessons from a case treated with a drug thought a teratogen].

PMID- 15559536
TI  - [Necessity of liquor diagnostics at the bed-side].

PMID- 15559537
TI  - [From ethics to law].

PMID- 15559538
TI  - [The EU clinical trial directive and its implementation in France].

PMID- 15559539
TI  - [Research with direct individual benefit or the individual benefit of research?].

PMID- 15559540
TI  - [Money and clinical trials].

PMID- 15559541
TI  - [Evaluation of decision-making by CCPPRBs].
AB  - OBJECTIVES: The aim of this study was to analyse the way in which 19 committees
      for the protection of people participating in biomedical research (CCPPRBs)
      develop their opinions and to determine whether the legitimacy of the decisions
      taken is based on detailed discussion by the various members of the committee.
      METHODS: An independent evaluator visited 19 CCPPRBs and attended two sessions at
      each centre. He investigated the functioning of the CCPPRBs both theoretically
      and in practice during the sessions, using a standardised data collection grid.
      RESULTS: The ethics of discussion are difficult to implement in these committees
      for four reasons: (i) a lack of training of the members; (ii) comments during
      sessions are rare (15% of all comments); (iii) too many dossiers are dealt with
      per session, resulting in some dossiers not being discussed in session; and (iv)
      there are too few nonscientific members, with the scientific members and the
      president playing a predominant role in the debates.

PMID- 15559542
TI  - [Ethical constraints of clinical trials in developing countries: experience of
      the French National Agency for AIDS Research (ANRS)].
AB  - The ethical principles of clinical research in the developing countries have
      recently been revised in most international guidelines. Their implementation
      leads to practical difficulties in the field. As an institutional sponsor, the
      French National Agency for AIDS Research (ANRS), responsible for research on AIDS
      and hepatitis in France and in the developing countries, released an Ethical
      Charter. It represents a commitment for the ANRS partners from the North and the
      South. The most important principles of the Charter are as follows: an early
      integration of research in the national programmes of public health; a strong
      partnership between North and South at any step of the research; a clear
      definition of rules concerning evaluation and ethical follow-up of the research;
      enrolment of the subjects; healthcare; care for the patients; and management of
      the post-study.

PMID- 15559543
TI  - [Ethical aspects of clinical trials and patient informed-consent sheet:
      HIV/AIDS].
AB  - The TRT-5 (Treatment and Therapeutic Research) group, created in 1992, is a
      coalition of eight advocacy and service-providing HIV/AIDS nongovernmental
      organisations (NGOs) [originally five NGOs] working together on treatment and
      research issues in the field of HIV/AIDS in France. After 11 years of work in the
      defending and advocating for the rights and the welfare of HIV+ individuals in
      the area of drug development and clinical research, we felt authorised to make
      comments and propose changes to the currently ongoing reform of the French Law
      (Loi Huriet) defining the legal framework of clinical research in France. Several
      of our proposals aiming to include into the new law solutions to many of the
      ethical problems we regularly face in clinical research have been incorporated
      into amendments submitted to Parliament during the first reading in the lower
      Chamber last October. Some of these amendments have been approved by the majority
      of deputies.

PMID- 15559544
TI  - [Medical research in paediatrics: ethical issues].
AB  - Since 1947 (the Nuremberg Code), the ethics of experimentation on human beings is
      based on the principle of the informed consent of the subjects participating in
      the research. In this context, research in paediatrics raised particular and
      difficult problems. International regulations have evolved in a way that has
      permitted paediatric research, within strict limits. However, recent studies have
      shown that the level of clinical paediatric research remains weak. There are
      economic reasons for this. But it also reveals the persistence of an ethical
      conflict: some people fear that a relativisation of the principle of consent
      (proxy consent) will lead to weakened protection for the most vulnerable
      subjects, including children. The ethics of responsibility requires a balance
      between the protection of the child as an individual (who should never become a
      medical guinea-pig) and the protection of children as a group (who should never
      be deprived of the benefits of the medical research).

PMID- 15559545
TI  - [Consent in paediatric clinical trials].

PMID- 15559546
TI  - [Phase I clinical trials in oncology: ethical issues].
AB  - The scientific goal of phase I clinical trials in oncology is to determine and
      optimise the drug dose and schedule on the basis of the toxicity profile. These
      trials also respond to a need: they offer the chance of early access to a new
      therapy for cancer patients who are characterised by both the lack of a
      therapeutic option and a desire to fulfil personal ambitions. The therapeutic
      relationship in this context must reconcile unreasonable hopes and anxiety
      regarding death and follow the same rules as in other doctor-patient
      relationships, with the triple requirement being that it should be genuine,
      therapeutic and empathetic.

PMID- 15559547
TI  - [Ethical restrictions and informed consent in intensive care].

PMID- 15559548
TI  - [The domiciliary medication management review: is it possible in France?].
AB  - From October 2001, the Australian healthcare system has made provision for, in
      predefined circumstances, a domiciliary medication review service. This
      pharmaceutical care service provides a medication review for outpatients
      encountering (or who may encounter) difficulties with their treatments, and who
      are referred by their physician. The pharmacist is chosen by the outpatient.
      Doctor and pharmacist gather the relevant elements of his/her medical file and
      work together, following procedures. After the consultation, the pharmacist
      passes his evaluation of the situation and his proposals to the doctor, who
      writes an action plan (shared with the pharmacist) and puts it into practice.
      This operational network is managed by the healthcare system. The 35000
      consultations carried out confirm the interest in this service and make it
      possible to simplify the treatments. The cost of the operation is more than
      covered by the savings generated. This discussion proposes to specifically study
      the transposition of this service to France.

PMID- 15559549
TI  - [Focus on biological agents in rheumatoid arthritis: newer treatments and
      therapeutic strategies].
AB  - Tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 are major regulators of
      inflammation. TNFalpha inhibitors have been shown to be effective in treating
      some inflammatory diseases such as rheumatoid arthritis. TNFalpha inhibitors
      include soluble receptor antagonists (etanercept) and monoclonal antibodies
      (infliximab, adalimumab). IL-1 inhibitors (anakinra) were also developed, used in
      therapeutics and licensed in France. TNFalpha inhibitors can be added to
      background regimens of methotrexate in second-line treatments. Etanercept and
      adalimumab can be administered alone, especially to patients who have experienced
      methotrexate toxicity or who do not show clinical and/or radiological
      improvement. The use of these new agents may optimise rheumatoid arthritis
      treatment and delay disease progression, particularly when first-line treatments
      are disappointing. This paper reviews recent data on biological therapies for
      rheumatoid arthritis: tolerance and their ability to modify the course of disease
      and prevent radiological damage.

PMID- 15559550
TI  - [Dyslipidaemia and its management after immunosuppressive treatment].
AB  - This article summarises the mechanisms responsible for the hyperlipidaemia
      observed after immunosuppressive treatment. Much progress has been achieved in
      the treatment of organ transplantation over the last 10 years, in particular
      because of the use of new immunosuppressive drugs with less nephrotoxicity.
      However, hypercholesterolaemia and hypertriglyceridaemia persist among many
      patients, who are thus more likely to develop cardiovascular diseases. We first
      reviewed the effects of immunosuppressive drugs on biliary acid biosynthesis,
      which is the main pathway of cholesterol degradation. The inhibition of this
      biosynthesis pathway, and especially of some key cytochrome P450s (CYP) such as
      CYP27A1, could contribute to the increased cholesterolaemia. Immunosuppressive
      drugs may also modify the activity of lipoprotein receptors or the expression of
      different apolipoproteins involved in cholesterol and triglyceride transport by
      lipoproteins. Finally, the fact that hypertriglyceridaemia is more frequently
      observed after certain immunosuppressive treatments may be partly caused by
      changes in the synthesis and elimination of triglycerides involving lipoprotein
      lipase or some apolipoproteins which serve as its cofactors (apoCII or apoCIII).

PMID- 15559551
TI  - [Effects of inorganic nitrates on thyroid gland activity and morphology in female
      rats].
AB  - The present study was undertaken to determine the effects of intake of inorganic
      nitrates in drinking water on thyroid gland activity and morphology in female
      rats. During 5 months of treatment, nitrates 50, 150 and 500 mg/L induced a
      significant dose-dependent decrease in bodyweight gain, compared with the control
      rats. At the end of the experiment, nitrates 150 and 500 mg/L induced hypertrophy
      of the thyroid gland, accompanied by an increase in the size of the thyroid
      follicles and hyposecretion of thyroid hormones T3 (triiodothyronine) and T4
      (tetraiodothyronine). We concluded that a high nitrate intake in water influenced
      thyroid gland activity and morphology and might be considered to be a goitrogenic
      factor.

PMID- 15559552
TI  - [Superior vena cava syndrome and methysergide].

PMID- 15559553
TI  - Efficacy of dapsone in an adolescent with chronic autoimmune thrombocytopenia.

PMID- 15559554
TI  - [Extrapyramidal syndrome worsened by tianeptine].

PMID- 15559555
TI  - Uighur traditional medicine syndrome of Abnormal Savda in men is associated with
      oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda.

PMID- 15559558
TI  - Clarification to SSRI table.

PMID- 15559559
TI  - Tips for public speaking.

PMID- 15559560
TI  - A case of possible facial cellulitis.

PMID- 15559561
TI  - Male factor infertility: an overview of issues.

PMID- 15559562
TI  - A pain in the neck: evaluation and management of cervical problems in older
      adults.

PMID- 15559563
TI  - Preventing falls: modifications can help.

PMID- 15559564
TI  - Distance learning diary.

PMID- 15559565
TI  - When theory meets practice: a philosophical approach to precepting the nurse
      practitioner student.

PMID- 15559566
TI  - New kid on the block: mentoring and networking as survival strategies for novice
      NPs.

PMID- 15559567
TI  - Chronic atrophic pyelonephritis in children.

PMID- 15559568
TI  - Antiretroviral update: recent advances expand options for patients with HIV.

PMID- 15559569
TI  - [Origin of bilateral-symmetrical animals (Bilateria)].
AB  - The paper is an attempt to attack the old problem of the origin of Bilateria by
      the methods of evolutionary tetrad (i.e. combination of comparative anatomy,
      comparative embryology, paleontology, and molecular biology). Three groups of
      theories of classical comparative anatomy (planulod-turbellarian, archicoelomate,
      and metameric) are discussed. Comparative embryology brings out clearly that the
      ventral side of embryo comes from the blastoporal region in all groups of
      Bilateria (except Chordata, where the blastoporal region corresponds to the
      dorsal side that is come out of the upside-down morphology of chordates) and
      mouth and anus comes from the anterior and posterior ends of elongated
      blastopore. From the point of view of paleontology, some of vendian metazoans
      demonstrate transitional conditions between the Radiata and Bilateria. Vendian
      bilaterians are metameric organisms with normal or asymmetric position of
      segments and could be pictured as "bilateral coelenterates" creeping on the oral
      surface. In Cnidaria, the expression of homologues of "Brachyury", "goosecoid",
      and "fork head" genes are revealed in the circular region around the mouth. In
      Bilateria, these genes are expressed along the elongated blastopore and around
      the mouth and anus. These results support the old conception on the amphistomic
      origin of mouth and anus as well as the homology between the oral disc of
      cnidarians and ventral side of Bilateria. The combination of four mentioned
      approaches enables us to propose the conception of the origin of Bilateria from
      vendian bilateral coelenterates with numerous metameric pouches of gastral
      cavity. Bilaterian ancestors crawled on the oral disc (= ventral side). These
      ancestors gave rise to both phanerosoic cnidarians and triploblastic bilaterians.
      Cnidarian ancestors attached to bottom by the aboral pole with the resulting
      degradation of aboral nerve ganglion. Bilateral symmetry of anthozoans is
      considered to be primitive feature for cnidarians. In case of triploblastic
      Bilateria, the elongated blastopore closed in the middle and subdivided into
      mouth and anus (amphistomy) and gastral pouches separated from the central part
      of gastral cavity and transformed to metameric coelomic chambers. The primary
      bilaterians are supposed to be complicated organisms having coelom and
      segmentation. The complexity of primary Bilateria provides an explanation for the
      abundance of highly organized organisms (arthropods, mollusks etc.) in Cambrian
      time. It is postulated that Ctenophora is the only group recent eumetazoans with
      primary axial symmetry.

PMID- 15559570
TI  - [Transport dependence of leaf evolution in dicots].
AB  - The diversity of tissue and cell organization in the leaves of dicots is
      explained as the mutual effect of light and water fluxes distribution. Equally
      with certain data about the role of light distribution, the same influence of
      water flux distribution on the leaf structure is recognized. Dorsiventral leaves
      of woody plants have an adequate to structure dorsiventral ring of water
      circulation. Rising flux from the xylem allocates via leaf apoplast with
      intermediate accumulation in upper epiderma. Descending flux starts and returns
      to bundle moving from cell to cell along the symplast (ER) of spongy parenchyma,
      bundle sheath and terminal complexes of the phloem. Isolateral leaves of herbs
      have a concentric pathway of solute circulation corresponding to the structure.
      Xylem flux allocates via symplast with water and nitrogen accumulation in
      paraveinal parenchyma. Water returns to phloem by transit via the apoplast in
      parallels with phloem exudate formation. Structural features correlated with the
      model of water circulation in the leaf are described. Numerous lines of leaf
      evolution well-known for dicots collect to two main topics which are typical for
      woody and herbaceous forms of dicots. The mechanisms of cell and tissue
      differentiation under the control of transport fluxes are discussed with special
      attention to ontogenetic and phylogenetic trends.

PMID- 15559571
TI  - [Spatial distribution of rare species: statistical approach].
AB  - Many species are locally rare (have low occurrences in a given region). The
      method is proposed for the analysis of spatial distribution of such species. The
      procedure is based on the comparison of actual mean distances between records
      with Monte-Carlo-simulated mean distances expected for random occurrence pattern.
      The method was applied to two datasets: benthic macrofauna from the Barents and
      Kara Seas (Kucheruk, Kotov, 2002) and the Black Sea interstitial ciliates
      (original data). For both datasets, the number of rare species positively
      correlates with number of common species per site and with the total number of
      species. Furthermore (and irrespectively of total diversity pattern), rare
      species usually were locally clumped in their distribution: each of the species
      was mostly found at sites that were close together. This tendency, however, was
      significant for the macrofauna species but not for ciliates.

PMID- 15559572
TI  - [Adaptation and ecological resistance].
AB  - The notion fitness, widely used in genetics usually serves to measure a relative
      rate of organism reproduction. Another important character of an organism is its
      ecological resistance which is basically the product of macroevolution. It can be
      determined as a probability of an organism survival and participation in
      reproduction of the species. Ecological resistance determines the level of the
      accidental death of organisms that are genetically valuable. For the comparison
      of ecological resistance in different organisms and species the negative meanings
      of the Malthusian parameter can be used. Ecological resistance depends on the
      presence in genomes of essential genes and fairly complete sets of nonessential,
      or adaptive, genes which can reside in genomes both as "plus" and "minus"
      alleles. The recovery of complete sets of adaptive genes lost as a result of
      mutations and, thus, of a high level of ecological resistance in organisms is
      provided by genetic exchange between them. With respect to mutations leading to
      the increase in fitness the effect of genetic exchange is negative since it leads
      to the formation of recombination load, i.e. a decrease in fitness of the
      offspring. In microevolutionary processes, the elevation in ecological resistance
      level does not take place since it requires a long time for the formation of new
      genes and new elements of organization in the process of positive selection. At
      the same time, a constant recovery of a high level of ecological resistance of
      the species decreased as a result of mutations takes place in some individuals
      due to genetic exchange. Mutations affecting ecological resistance of an
      organism, as a rule, cause a decrease in its viability and they are usually
      excluded from populations as a result of negative (stabilizing) selection.

PMID- 15559573
TI  - [Social environment and morpho-physiological status of young males in the fall
      groups of great gerbil (Rhombomys opimus Licht). Effect of adults' presence].
AB  - The dependence of stress and sex hormone levels, size of mid-ventral skin gland,
      and body mass of young males on the presence in social groups of adult gerbils
      (>1 year old) were studied during the fall of 1999 in the non-breeding high
      density population of the great gerbil (Rhombomys opimus Licht; Bukhara region,
      Uzbekistan). Contents of corticosterone and testosterone in fecal samples
      collected from young males in the field were analyzed by non-invasive
      radioimmunoassay. The fall gerbil groups with adults were of larger size than
      those without adults. The total number of individuals in a group is positively
      correlated with concentration of corticosterone in feces of young males. Presence
      of adult male and especially of adult female suppresses maturation of juvenile
      males indicated by size of the androgene-dependent mid-ventral gland, but
      accelerates their total growth. Thus, the social environment influences morpho
      physiological characters of young males, effecting rate of their maturation
      directly or indirectly through the density dependent stress.

PMID- 15559574
TI  - [Structural and bioindicative aspects of fluctuated asymmetry of bilateral
      organisms].
AB  - We have proposed and validated a method for quantitative assessment of phenotypic
      diversity of natural populations. Method is based on the fluctuated asymmetry
      (FA) indices of bilateral organisms, and it is applicable for biondicative
      investigations. Convolution of functions was proposed to estimate the mean
      (population) value of FA complex of features. This function could be written as
      finit sum [formula: see text] where eta is power of sample invariance (symmetry)
      for m individuals (i = 1, m). Eta is characterized by n asymmetric
      characteristics (j = 1, n) for the left (L) and the right (R) sides of the body.
      We have validated applicability of generalized function of desirability [formula:
      see text] (where di is partial desirability function [0,1]) for cumulative
      characterization of environment quality with results of bioindicative
      investigations. The value of function coincides with the value of symmetry of
      indicating species in this case.

PMID- 15559575
TI  - Presenteeism: at work--but out of it.
AB  - Employers are beginning to realize that they face a nearly invisible but
      significant drain on productivity: presenteeism, the problem of workers' being on
      the job but, because of illness or other medical conditions, not fully
      functioning. By some estimates, the phenomenon costs U.S. companies over 150
      billion dollars a year--much more than absenteeism does. Yet it's harder to
      identify. You know when someone doesn't show up for work, but you often can't
      tell when, or how much, poor health hurts on-the-job performance. Many of the
      health problems that result in presenteeism are relatively benign. Research in
      this emerging area of study focuses on such chronic or episodic ailments as
      seasonal allergies, asthma, headaches, depression, back pain, arthritis, and
      gastrointestinal disorders. The fact is, when people don't feel good, they simply
      don't perform at their best. Employees who suffer from depression may be fatigued
      and irritable--and, therefore, less able to work effectively with others. Those
      with migraine headaches who experience blurred vision and sensitivity to light,
      not to mention acute pain, probably have a hard time staring at a computer screen
      all day. A number of companies are making a serious effort to determine the
      prevalence of illnesses and other medical conditions that undermine job
      performance, calculate the related drop in productivity, and find cost-effective
      ways to combat that loss. Indeed, researchers have discovered that presenteeism
      related declines in productivity sometimes can be more than offset by relatively
      small investments in screening, treatment, and education. So organizations may
      find that it pays to make targeted investments in employees' health care--by
      covering the cost of allergy medication, for instance, or therapy for depression.

PMID- 15559576
TI  - Seven surprises for new CEOs.
AB  - As a newly minted CEO, you may think you finally have the power to set strategy,
      the authority to make things happen, and full access to the finer points of your
      business. But if you expect the job to be as simple as that, you're in for an
      awakening. Even though you bear full responsibility for your company's well
      being, you are a few steps removed from many of the factors that drive results.
      You have more power than anybody else in the corporation, but you need to use it
      with extreme caution. In their workshops for new CEOs, held at Harvard Business
      School in Boston, the authors have discovered that nothing--not even running a
      large business within the company--fully prepares a person to be the chief
      executive. The seven most common surprises are: You can't run the company. Giving
      orders is very costly. It is hard to know what is really going on. You are always
      sending a message. You are not the boss. Pleasing shareholders is not the goal.
      You are still only human. These surprises carry some important and subtle
      lessons. First, you must learn to manage organizational context rather than focus
      on daily operations. Second, you must recognize that your position does not
      confer the right to lead, nor does it guarantee the loyalty of the organization.
      Finally, you must remember that you are subject to a host of limitations, even
      though others might treat you as omnipotent. How well and how quickly you
      understand, accept, and confront the seven surprises will have a lot to do with
      your success or failure as a CEO.

PMID- 15559577
TI  - Blue ocean strategy.
AB  - Despite a long-term decline in the circus industry, Cirque du Soleil profitably
      increased revenue 22-fold over the last ten years by reinventing the circus.
      Rather than competing within the confines of the existing industry or trying to
      steal customers from rivals, Cirque developed uncontested market space that made
      the competition irrelevant. Cirque created what the authors call a blue ocean, a
      previously unknown market space. In blue oceans, demand is created rather than
      fought over. There is ample opportunity for growth that is both profitable and
      rapid. In red oceans--that is, in all the industries already existing--companies
      compete by grabbing for a greater share of limited demand. As the market space
      gets more crowded, prospects for profits and growth decline. Products turn into
      commodities, and increasing competition turns the water bloody. There are two
      ways to create blue oceans. One is to launch completely new industries, as eBay
      did with online auctions. But it's much more common for a blue ocean to be
      created from within a red ocean when a company expands the boundaries of an
      existing industry. In studying more than 150 blue ocean creations in over 30
      industries, the authors observed that the traditional units of strategic analysis
      -company and industry--are of limited use in explaining how and why blue oceans
      are created. The most appropriate unit of analysis is the strategic move, the set
      of managerial actions and decisions involved in making a major market-creating
      business offering. Creating blue oceans builds brands. So powerful is blue ocean
      strategy, in fact, that a blue ocean strategic move can create brand equity that
      lasts for decades.

PMID- 15559578
TI  - How industries change.
AB  - It's fairly obvious: To make intelligent investments within your organization,
      you need to understand how your whole industry is changing. But such knowledge is
      not always easy to come by. Companies misread clues and arrive at false
      conclusions all the time. To truly understand where your industry is headed, you
      have to take a long-term, high-level look at the context in which you do
      business, says Boston University professor Anita McGahan. She studied a variety
      of businesses from a cross section of industries over a ten-year period,
      examining how industry structure affects business profitability and investor
      returns. Her research suggests that industries evolve along one of four distinct
      trajectories--radical, progressive, creative, and intermediating--that set
      boundaries on what will generate profits in a business. These four trajectories
      are defined by two types of threats. The first is when new, outside alternatives
      threaten to weaken or make obsolete core activities that have historically
      generated profits for an industry. The second is when an industry's core assets-
      its resources, knowledge, and brand capital--fail to generate value as they once
      did. Industries undergo radical change when core assets and core activities are
      both threatened with obsolescence; they experience progressive change when
      neither are jeopardized. Creative change occurs when core assets are under threat
      but core activities are stable, and intermediating change happens when core
      activities are threatened while core assets retain their capacity to create
      value. If your company's innovation strategy is not aligned with your industry's
      change trajectory, your plan for achieving returns on invested capital cannot
      succeed, McGahan says. But if you understand which path you're on, you can
      determine which strategies will succeed and which will backfire.

PMID- 15559579
TI  - The triple-A supply chain.
AB  - Building a strong supply chain is essential for business success. But when it
      comes to improving their supply chains, few companies take the right approach.
      Many businesses work to make their chains faster or more cost-effective, assuming
      that those steps are the keys to competitive advantage. To the contrary: Supply
      chains that focus on speed and costs tend to deteriorate over time. The author
      has spent 15 years studying more than 60 companies to gain insight into this and
      other supply chain dilemmas. His conclusion: Only companies that build supply
      chains that are agile, adaptable, and aligned get ahead of their rivals. All
      three components are essential; without any one of them, supply chains break
      down. Great companies create supply chains that respond to abrupt changes in
      markets. Agility is critical because in most industries, both demand and supply
      fluctuate rapidly and widely. Supply chains typically cope by playing speed
      against costs, but agile ones respond both quickly and cost-efficiently. Great
      companies also adapt their supply networks when markets or strategies change. The
      best supply chains allow managers to identify structural shifts early by
      recording the latest data, filtering out noise, and tracking key patterns.
      Finally, great companies align the interests of the partners in their supply
      chains with their own. That's important because every firm is concerned solely
      with its own interests. If its goals are out of alignment with those of other
      partners in the supply chain, performance will suffer. When companies hear about
      the triple-A supply chain, they assume that building one will require increased
      technology and investment. But most firms already have the infrastructure in
      place to create one. A fresh attitude alone can go a long way toward making it
      happen.

PMID- 15559580
TI  - Leading a supply chain turnaround.
AB  - Just five years ago, salespeople at Whirlpool were in the habit of referring to
      their supply chain organization as the "sales disablers." Now the company excels
      at getting products to the right place at the right time--while managing to keep
      inventories low. How did that happen? In this first-person account, Reuben Slone,
      Whirlpool's vice president of Global Supply Chain, describes how he and his
      colleagues devised the right supply chain strategy, sold it internally, and
      implemented it. Slone insisted that the right focal point for the strategy was
      the satisfaction of consumers at the end of the supply chain. Most supply chain
      initiatives do the opposite: They start with the realities of a company's
      manufacturing base and proceed from there. Through a series of interviews with
      trade customers large and small, his team identified 27 different capabilities
      that drove industry perceptions of Whirlpool's performance. Knowing it was
      infeasible to aim for world-class performance across all of them, Slone weighed
      the costs of excelling at each and found the combination of initiatives that
      would provide overall competitive advantage. A highly disciplined project
      management office and broad training in project management were key to keeping
      work on budget and on benefit. Slone set an intense pace--three "releases" of new
      capabilities every month--that the group maintains to this day. Lest this seem
      like a technology story, however, Slone insists it is just as much a "talent
      renaissance." People are proud today to be part of Whirlpool's supply chain
      organization, and its new generation of talent will give the company a
      competitive advantage for years to come.

PMID- 15559581
TI  - America's looming creativity crisis.
AB  - The strength of the American economy does not rest on its manufacturing prowess,
      its natural resources, or the size of its market. It turns on one factor--the
      country's openness to new ideas, which has allowed it to attract the brightest
      minds from around the world and harness their creative energies. But the United
      States is on the verge of losing that competitive edge. As the nation tightens
      its borders to students and scientists and subjects federal research funding to
      ideological and religious litmus tests, many other countries are stepping in to
      lure that creative capital away. Ireland, Canada, Australia, New Zealand,
      Denmark, and others are spending more on research and development and shoring up
      their universities in an effort to attract the world's best--including Americans.
      If even a few of these nations draw away just a small percentage of the creative
      workers from the U.S., the effect on its economy will be enormous. In this
      article, the author introduces a quantitative measure of the migration of
      creative capital called the Global Creative-Class Index. It shows that, far from
      leading the world, the United States doesn't even rank in the top ten in the
      percentage of its workforce engaged in creative occupations. What's more, the
      baby boomers will soon retire. And data showing large drops in foreign student
      applications to U.S. universities and in the number of visas issued to knowledge
      workers, along with concomitant increases in immigration in other countries,
      suggest that the erosion of talent from the United States will only intensify. To
      defend the U.S. economy, the business community must take the lead in ensuring
      that global talent can move efficiently across borders, that education and
      research are funded at radically higher levels, and that we tap into the creative
      potential of more and more workers. Because wherever creativity goes, economic
      growth is sure to follow.

PMID- 15559582
TI  - Cultural intelligence.
AB  - In an increasingly diverse business environment, managers must be able to
      navigate through the thicket of habits, gestures, and assumptions that define
      their coworkers' differences. Foreign cultures are everywhere--in other
      countries, certainly, but also in corporations, vocations, and regions.
      Interacting with individuals within them demands perceptiveness and adaptability.
      And the people who have those traits in abundance aren't necessarily the ones who
      enjoy the greatest social success in familiar settings. Cultural intelligence, or
      CQ, is the ability to make sense of unfamiliar contexts and then blend in. It has
      three components--the cognitive, the physical, and the emotional/motivational.
      While it shares many of the properties of emotional intelligence, CQ goes one
      step further by equipping a person to distinguish behaviors produced by the
      culture in question from behaviors that are peculiar to particular individuals
      and those found in all human beings. In their surveys of 2,000 managers in 60
      countries, the authors found that most managers are not equally strong in all
      three of these areas of cultural intelligence. The authors have devised tools
      that show how to identify one's strengths, and they have developed training
      techniques to help people overcome weaknesses. They conclude that anyone
      reasonably alert, motivated, and poised can attain an acceptable CQ.

PMID- 15559583
TI  - Concerning the current high demand for snake oil.

PMID- 15559584
TI  - Policy statements on oral health.

PMID- 15559586
TI  - Disparities in access to oral health care and disparities in oral health status.

PMID- 15559585
TI  - Adequate and affordable dental health in California.

PMID- 15559587
TI  - Oral and maxillofacial surgery--character of the specialty.
AB  - Because of its similarities to other disciplines in dentistry and to medicine,
      the boundaries of oral and maxillofacial surgery are not easily defined. Some of
      the characteristics of the specialty include depth of the medical and biological
      knowledge of patients required, competitive selection and extensive training,
      hospital training and practice, and well articulated standards and support from
      its professional organization, the American Association of Oral and Maxillofacial
      Surgeons.

PMID- 15559588
TI  - Commentary after thirty years of private practice in oral surgery.
AB  - Complexity and rapid development make oral and maxillofacial surgery the most
      unique specialty. From the perspective of thirty years of private practice, the
      author reflects on the necessity to blend science, practice, and business to meet
      patient needs. The special role of pain management is described. The change to
      oral and maxillofacial surgery that occurred roughly twenty years ago reflects
      the rapid expansion of knowledge, complexity of cases, and use of technology.
      Some of the issues that must to addressed in the future of the specialty include
      managing costs of education and practice with reimbursement trends, defining the
      scope of practice, and promoting research and technology and incorporating it in
      practice.

PMID- 15559589
TI  - On becoming a surgeon.
AB  - A dentist who has just completed eight years of oral and maxillofacial residency
      training reflects on what drew him to the specialty and how it changed him. He
      notes three characteristics of his training that differed from predoctoral
      education and help define a surgeon: patient-based learning, learning from
      constant discussions with colleagues, and the habit of facing unexpected outcomes
      as a source of learning.

PMID- 15559590
TI  - Improving communication through publications: contributions of American oral and
      maxillofacial surgery.
AB  - The Journal of Oral Surgery was the first specialty publication in the United
      States and since 1943 it, its successor, the Journal of Oral and Maxillofacial
      Surgery, and other publications of the American Association of Oral and
      Maxillofacial Surgeons have been committed to communication within the specialty,
      among dental specialties, and with dentists in general practice. A review of back
      issues of the journal is a history of the development of the specialty. AAOMS
      publications are intended to share emerging scientific and clinical knowledge,
      inform and educate all dentists, and establish standards for quality patient
      care.

PMID- 15559591
TI  - The morbidity and mortality conference: a case assessment tool, quality control
      measure, and teaching method.
AB  - The morbidity and mortality conference and other traditions in hospital-based
      training inculcate the habits of understanding evidence and its clinical
      application and being able to articulate these to one's peers and to learn from
      unanticipated outcomes. By contrast, predoctoral dental training and the
      environment of general dental practice do not encourage collegial reflection on
      the outcomes of practice. Benefits and cautions in applying the habits learned
      through M&M conferences are discussed for both the oral and maxillofacial and the
      general practice settings.

PMID- 15559592
TI  - In whose interest?

PMID- 15559593
TI  - Conflicts of interest.
AB  - Conflicts of interest are unavoidable in dentistry. A set of five questions is
      offered to help sort through such conflicts. The potential harm and the
      likelihood of such harm caused by secondary interests (the potentially
      conflicting ones) must be considered against the potential harm and the
      likelihood of damage caused by withholding services in which secondary interests
      are present. The use of these questions is illustrated with an example of a
      researcher who has a commercial interest in the product under study and of
      dentists who have secondary interests in services provided to patients.

PMID- 15559594
TI  - Rhetoric.
AB  - Persuasion is the art of giving others reasons to believe you. Classically, the
      three elements of rhetoric have been evidence or a strong case, connecting with
      and honoring the feelings of the audience, and character--the person and the
      message always come together as a package. Twenty types of common abuse and
      misuse of rhetoric are discussed. Rhetoric involves the ethical principle of
      allowing others to believe without forcing them to do so. It is essential to
      democratic societies.

PMID- 15559595
TI  - Et tu? Investigations also may target hospitals.

PMID- 15559596
TI  - Earth to hospitals. GPOs lead the way to green purchasing.

PMID- 15559597
TI  - Stretched thin.

PMID- 15559598
TI  - Combine & conquer.

PMID- 15559599
TI  - Money Matters.

PMID- 15559600
TI  - [Future of laparoscopy in colorectal cancer surgery].
AB  - Laparoscopic surgery has been associated with less postoperative pain, an early
      return of bowel function, a shorter period of hospitalization and disability, and
      better cosmetic results. In the past decade laparoscopic techniques are
      increasingly being applied to colorectal surgical procedures. Diagnostic
      laparoscopy, the creation of stomas, and limited resections are becoming
      reasonable indications for benign diseases. However, the application of
      laparoscopic techniques to the curative resection of colorectal cancer is still
      controversial, owing to reports of cancer recurrence at the port site wounds.
      Port-site recurrence remains a leading concern regarding the widespread
      acceptance of laparoscopic resection for colorectal carcinoma. The last reports
      has presented that with careful technique, training and experience wound
      recurrences are rarely seen, suggesting that this phenomenon is primarily
      technique and advanced cancer stages related. The final results of the large
      randomized prospective studies may well determine the role of laparoscopy for
      colorectal cancer in the near future.

PMID- 15559601
TI  - [Factors of physical development of healthy children in relation to 24-hour
      ambulatory blood pressure patterns].
AB  - The aim of this study was to assess which of the relationships between ambulatory
      blood pressure patterns and physical development factors in healthy children was
      the strongest and most significant. 24-hour ambulatory blood pressure monitoring
      (ABPM) was performed on 100 healthy children aged 10-18 years. Mean values of
      diurnal, nocturnal and 24-hour systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) were calculated on its basis. Correlation coefficients were
      calculated for the associations between these mean values and physical
      development factors: age, body mass, body height, body mass index (BMI) and BMI
      centile. SBP levels were the strongest and most significant, positively
      associated with values of BMI, body mass and BMI centile. The correlation with
      age was weaker and with body height the most weak. DBP levels correlated
      significantly only with BMI centile and showed relationship of bordering
      significance with BMI value. There were no significant correlations between DBP
      levels and age, body mass or body height. CONCLUSIONS: In children BMI and its
      centile correlate with ambulatory blood pressure levels stronger and more
      significant than other physical development factors. Three-dimensional centile
      charts including age, BMI and blood pressure level could be the most accurate in
      diagnosing hypertension.

PMID- 15559602
TI  - [Variety of initial symptoms in patients with Wegener's granulomatosis].
AB  - Wegener's granulomatosis is a necrotizing vasculitis with heterogenous initial
      symptoms what may still cause diagnostic problems. We present analysis of initial
      symptoms of 14 patients with Wegener's granulomatosis to evaluate their value in
      early diagnosis. Involvement of kidneys as well as upper and lower airways may
      suggest the diagnosis. Acute onset with intensified general symptoms may provoke
      more intensive diagnostic procedures and the diagnosis can be established
      earlier. In patients with non-acute onset the diagnosis may be delay, in some
      cases a few years after the first symptoms.

PMID- 15559603
TI  - [Early postoperative complications in patients with aneurysm of the abdominal
      aorta treated with vascular prosthesis].
AB  - Type and frequency of early postoperative complications were analyzed in a group
      of 226 patients (190 men and 36 women) at the age of 45 to 83 (mean age 65.3 +/-
      8.2) who were operated as planned due to aneurysm of abdominal part of aorta.
      Patients were divided into two groups (I and II) depending on method of
      analgesia. Group I which constituted 173 patients operated at associated general
      and extrameningeal analgesia and group II constituted 53 patients operated at
      general analgesia. The division into groups was unintentional and was due to the
      fact that general analgesia was carried out in patients with contraindication of
      extrameningeal catheter use or technical troubles with its appliance. Patients of
      both groups were divided into groups (A and B) depending on type of complication
      or cause of death (A--cardiogenic, B--extracardiac). The followed up group is
      characterized by increased incidence in men than in women (5:1), the age of both
      sexes is not significantly different respectively men and women 65.5 and 65.2
      years. In most cases, patients suffered from arterial hypertension (20.4%),
      ischaemic heart disease and myocardial infarction (21.2%) and chronic obstructive
      lung disease (12%). Early postoperative complications without lethal outcome
      occurred in 76 patients (33.6%), in 7.5% they included cardiogenic complications,
      while in 26% extracardiac complications, among which acute ischaemia of lower
      extremities (8.8%) and postoperative pulmonary complications (5.7%) were the most
      dominating. The observed group is characterized by relatively high postoperative
      mortality (9.3%). 4% of patients died due to cardiogenic reasons, while 5.3% of
      patients died due to extracardiac reasons. The most common cause of death in the
      last group was infection and embolism of mesentery (3.6%). Strong relation
      between preoperative loading, operation time, time of aorta occlusion, type of
      grafted prosthesis and frequency as well as type of postoperative complications
      was confirmed. The relationship was not confirmed with respect to the type of
      analgesia.

PMID- 15559604
TI  - [Effectiveness of treatment of varicose veins assessed by epidemiological
      comparative studies].
AB  - Effectiveness of varicose veins (VV) management, due to high prevalence of this
      condition, is an important medical, social and economical issue. The aim of the
      study was to compare cost effectiveness of VV treatment by comparison of the
      results of two epidemiological surveys performed in Warsaw Brodno population, in
      1982-1984 (group I, n=4997) and 1998-2000 (group 11, n=3556). Analysis compared
      prevalence of varicose veins, venous ulcers, deep vein thrombosis (DVT) in
      relation to number of VV procedures performed, and cost of conservative and
      surgical treatment, subjective patients' assessment of treatment results.
      Varicose veins prevalence has not changed significantly in group I was 15.7% (men
      9.3%, women 20.1%) vs. 13.7% (men 8.7%, women 15.9%) in group II. Similarly,
      prevalence of venous ulcers (0.76% vs 0.73%), and previous DVT among VV patients
      (8.9% vs 8.9%) have not changed in both groups. Percentage of patients treated
      surgically in relation to all VV patients (19.7% vs 26.1%), as well as treated
      conservatively (45.2% vs 48.8%) increased, the latter mainly due to significant
      increase of ratio of patients treated with phlebotropic drugs.
      Patients'assessment of conservative and surgical treatment has improved
      dramatically, cost of treatment remained similar. Despite significant surgical
      and conservative treatment efforts, prevalence of essential venous diseases in
      hospital catchment area remained unchanged. Amount of patients satisfied both
      with surgical and conservative treatment increased, perhaps mainly due to better
      efficacy of phlebotropic drugs and better access to specialist care. On the other
      hand, significant amount of patients doesn't start any treatment at all. We
      conclude that preventive varicose veins surgery during early stage of disease may
      not diminish prevalence of serious venous complications.

PMID- 15559605
TI  - [Vitamin E status in mothers of children with cleft lip].
AB  - It had been suspected for many years that mother's periconceptional diet may have
      a role in the causation of birth defects. Over the past 10 years, many studies
      have reported that women who used multivitamins periconceptionally had a
      reduction in risk for offspring with orofacial cleft. This study was aimed to
      establish vitamin E status in Polish mothers of children with isolated cleft lip.
      37 mothers of children with cleft lip (CL) and 67 women who gave birth to healthy
      children were studied. All participants were healthy women without symptoms of
      malabsorption. Levels of alpha-tocopherol in plasma and erythrocytes were
      determined by high-performance liquid chromatography. There was no differences
      between mean plasma alpha-tocopherol level in mothers of children with birth
      defect and mothers of healthy children (17.81 +/- 4.81 micromol/l vs 19.44 +/-
      5.01 micromol/l; p>0.05). It is believed that the ratio of alpha-tocopherol to
      total cholesterol is more useful as a measure of vitamin status than the a
      tocopherol level alone. In mothers of children with CL plasma alpha-tocopherol to
      total serum cholesterol ratio was statistically lower compared to those in the
      control group (3.35 +/- 0.88 micromol/mmol vs 3.89 +/- 0.79 micromol/mmol;
      p<0.02). Ratio of alpha-tocopherol level in erythrocytes to total serum
      cholesterol was also lower in mothers of children with CL (0.38 +/- 0.06
      micromol/mmol vs 0.48 +/- 0.10 micromol/mmol; p<0.05). Our results suggested that
      vitamin E may play a role in prevention of orofacial clefts.

PMID- 15559606
TI  - [Development of binding antibodies to interferon-beta during treatment of
      multiple sclerosis with different types of interferon-beta].
AB  - Interferon beta (IFN-beta) is generally considered an effective treatment for
      multiple sclerosis (MS). Importance of binding antibodies (BAb), which are
      created during the treatment of MS by the use of IFN-beta, hasn't been completely
      explained, however it is generally reckoned that they might be one of the factors
      diminishing treatment efficacy. The aim of the study was the appreciation of BAb
      occurrence during the treatment of MS by the use of different types of interferon
      beta and their impact on clinical efficacy. The study included 47 patients with
      relapsing-remitting MS. Within 24 months 37 patients were given two different
      preparations of IFN-beta 1-a and 10 patients were given IFN-beta 1-b. Every 6
      months clinical parameters and BAb level in serum by EIA method were estimated.
      All preparations of IFN-beta induced appearance of BAb, but frequency of
      developing BAb to IFN-beta varied according to the IFN beta given. The high
      levels of BAb appeared significant frequently in patients treated with IFN-beta 1
      b than in patients treated with both preparations of IFN-beta 1-a. After 2 years
      of treatment greater disability, measured by EDSS scale was encountered in
      patients with high levels of BAb but differences weren't statistically
      significant. As well, it wasn't stated significant correlation between
      exacerbation numbers during the treatment.

PMID- 15559607
TI  - [Incidence of acute pancreatitis in children with inflammatory bowel disease].
AB  - The aim of our study was to estimate the frequency of acute pancreatitis and the
      frequency of increased activity of pancreatic enzymes in serum of children with
      inflammatory bowel disease (IBD). Analysis comprises 101 children aged from 3 to
      18-years treated because of IBD in the period of 1998-2002: 79 children with
      ulcerative colitis (UC) and 22 children Crohn's disease (CD). The authors
      analyzed together 191 admissions because of UC and 51 because of CD. Acute
      pancreatitis was observed in 4.5% of children with CD and in 5.1% of children
      with UC. Significantly more often acute pancreatitis was recognized in children
      with moderate and severe stage of UC. Hyperamylasemia was observed in 27.3% of
      children with CD and in 12.7% of children with UC. Hyperlipasemia was observed
      only in children with UC (3.8%), elevated urinary amylase was observed in 4.5% of
      children with CD and in 8.86% children with UC. No correlations between the
      frequency of acute pancreatitis and medication were observed.

PMID- 15559608
TI  - [Bone mineral density in children before and after completion of cancer
      treatment].
AB  - This study was performed to determine the degree of osteopenia in children with
      malignancy before and after completion of treatment. Twenty six subjects (17
      male, 9 female) treated for acute lymphoblastic leukemia (n=15),
      lymphogranulomatosis maligna (n=7) or solid tumor (n=4) at a mean age 9.34 (range
      3-17.41 years) before and 15.85 (range 9.66-23) after treatment participated in
      this longitudinal study. Mean follow up period after discontinuation of therapy
      was 5.5 years (range 2.6-8.3 years). Interview (estimation of physical activity,
      other chronic disease, and fractures), anthropometric measurements of body mass
      and height, body mass index (BMI), bone mineral density total (BMD Total) and
      spine (BMD Spine) were obtained from every child. Gained findings were compared
      to the same parameters in the group of 473 healthy children, comparable in age
      and gender with examined group and showed as SD score. There were no differences
      in BMI and BMD Total and Spine between patients and controls. No correlation was
      found between the BMD values and the diagnosis, age at diagnosis, gender and
      cranial irradiation and duration of follow-up. BMD Spine SD score was
      significantly increased in a subgroup of patients in pubertal stage at diagnosis
      as compared to patients in prepubertal stage. Further studies are needed to
      evaluate the long-term effect on BMD in patients with cancer and how to prevent a
      decrease of BMD.

PMID- 15559609
TI  - [Comparison of the effectiveness of electrovaporisation, vaporesection and
      electroresection in the treatment of obstructive symptoms in patients with benign
      prostate hyperplasia].
AB  - OBJECTIVES: The aim of this study is the comparison of the efficacy of classical
      electroresection of the prostate (TURP) and its modern modifications-
      electrovaporisation (EVAP) and vaporesection (TUVRP) in the treatment of patients
      with benign prostate hyperplasia (BPH). MATERIAL AND METHODS: 96 patients were
      operated on because of BPH. In 31 patients we performed TURP (group I), in 34-
      EVAP (group II) and in 31--TUVRP (group III). On follow up 1, 3, 6 months post
      operation we evaluated maximal urine flow (Qmax) and postvoid residual urine
      (PVR) and compared them to preoperation values. RESULTS: Mean preoperative values
      were: 8.98 ml/s and 116.76 ml (group I); 8.64 ml/s and 121.36 ml (group II) and
      8.69 ml/s and 112.50 ml (group III). In all patients after 1 month follow up Qmax
      raised almost twice and after 6 months mean values were respectively in groups I,
      II, III: 21.62 ml/s; 20.79 ml/s; 22.56 ml/s. PVR diminished in 6 months follow up
      and mean values were respectively 14.61 ml; 15 ml; 11.25 ml. Differences in these
      results were of no statistical value. CONCLUSIONS: The efficacy of TURP, EVAP and
      TUVRP in the treatment of BPH is comparable. EVAP and TUVRP also diminished risk
      of intraoperative bleeding.

PMID- 15559610
TI  - [Transvaginal ultrasonography and sonohysterography in the diagnosis of benign
      uterine lesions in women at peri- and postmenopausal age].
AB  - Abnormal uterine bleeding is important clinical problem in women at peri- and
      postmenopausal age. It may be caused by the lesions located in endometrium or in
      deeper uterine wall layers. An aim of this paper was a comparison of transvaginal
      sonography (TVS) vs. sonohysterography (SIS) in the diagnostics of endometrial
      polyps, endometrial hyperplasia as well as uterine myomas. Also the results of
      the sonographic imaging were compared to those of pathologic examination of the
      specimens taken from the uterine cavity. The material consisted of 100 women aged
      40-80 with an irregular menstruation. All of the patients were examined
      gynecologically, and then the transvaginal sonography, sonohysterography and the
      curettage of the uterine cavity were performed. Sensitivity of TVS was 43% in
      endometrial polyps, 77% in endometrial hyperplasia and 69% in uterine myomas
      imaging. Introduction of SIS increased the sensitivity to 94%, 82%, and 95%,
      respectively. Specificity was similar in both techniques except endometrial
      hyperplasia (TVS--68%, SIS--91%). Diagnostic accuracy also improved with the SIS
      use reaching 93% for polyps, 89% for hyperplasia and 98% for myomas imaging. Our
      results show higher sensitivity and accuracy of SIS in the diagnostic of benign
      uterine lesions.

PMID- 15559611
TI  - [Circadian rhythm of melatonin in patients with hypertension].
AB  - Few reports, especially experimental ones indicate cause-effect connection
      between melatonin (Mel) and blood pressure. The aim of the study was to assess
      connection between a daily profile of Mel concentration in saliva and 24-hour
      cycle of blood pressure in 22 patients with moderate hypertension (12 men, 10
      women), 20 patients with severe hypertension (9 men, 11 women) and 25 healthy
      subjects with normal blood pressure (13 men, 12 women). The age of studied
      subjects oscillated between 37 and 46 years. Concentrations of Mel were assessed
      in saliva collected during the day with intervals of 3 hours with the use of RIA
      method. Blood pressure assessment was done at the same time. A significant
      decrease of mesor's value and amplitude of Mel rhythm without essential changes
      in acrophase's value were observed in men and women with severe hypertension.
      Mean concentrations of Mel in saliva were significantly decreased from 8 pm to 5
      am. Significant, negative correlation between nighttime Mel concentrations in
      saliva and both systolic and diastolic blood pressure was shown in patients with
      moderate and severe hypertension. Correlation coefficients values were in general
      higher in patients with severe hypertension. Results of our studies seem to
      confirm the conception that decreased Mel secretion can be one of the causes of
      hypertension.

PMID- 15559612
TI  - [Blood coagulation parameters in patients with lichen planus].
AB  - The aim of this study was to evaluate some blood parameters of coagulation
      process in blood plasma of patients suffering from lichen planus. The study group
      consisted of 23 patients--14 women and 9 men, aged 33-75 years. Control group
      contained 30-age matched healthy persons. In blood of plasma the following
      parameters were determined: activity of antithrombin III (AT III) and
      concentration of prothrombin fragments 1+2 (F1+2), complexes thrombin
      antithrombin III (TAT). In blood plasma of patients with lichen planus the
      concentration of F1+2 was significantly higher than in healthy persons. Increased
      concentration of F1+2 indicated intensive thrombinogenesis in vivo in patients
      with lichen planus.

PMID- 15559613
TI  - [Macrocytic megaloblastic anaemia in a patient with Helicobacter pylori
      infection].
AB  - We present 62 yrs old patient in whom megaloblastic anaemia due to vitamin B12
      depletion was caused by Helicobacter pylori infection. An eradication treatment
      with the vitamin B12 supplementation within 7 days resulted in withdrawal of the
      abnormalities in the blood smear. The inflammation of gastric mucosa with
      intestine metaplasia is still observed. According to the letters these changes
      may persist up to 2-3 years after treatment ending.

PMID- 15559614
TI  - [Late complication of endoscopy grafting of biliary tract].
AB  - We report a case of duodenal perforation localized in the lower flexure caused by
      biliary tract graft complicated by peritonitis. We described our management of
      this case. We discuss indications and complications of biliary tract grafting.

PMID- 15559615
TI  - [Fournier's gangrene in non-resectable colorectal carcinoma].
AB  - Fournier's gangrene is a necrotizing fasciitis of the genitalia and perineum.
      Primary inflammatory focus is usually located in the genitourinary tract, skin or
      anorectum. The gangrene is caused by a mixed bacterial flora. The management is
      based on surgical debridement, drainage and antibiotics. Despite of adequate
      treatment mortality is approximately 20%. We present a case of 65 year-old male
      with a non-resectable rectal carcinoma who developed Fournier's gangrene after a
      palliative operation because of intestinal obstruction. Several excisions of the
      necrotic tissues were performed resulting in significant local improvement. The
      patient died of disseminated carcinoma a few weeks after the last debridement
      procedure.

PMID- 15559616
TI  - [Role of total bladder resection and reconstructive surgery in children with soft
      tissue sarcomas--three clinical cases)].
AB  - Soft tissue tumors of the lower genitourinary tract in children require a
      multidisciplinary treatment. The international CWS-91 and CWS-96 protocols
      established the second-look operation as a control procedure. One of the surgical
      options is a total cystectomy followed by the subsequent genitourinary
      reconstruction. The article presents a short characteristic of the reconstructive
      method modo Studer, advantages connected with this procedure, possible
      complications as well as description of three clinical cases of children treated
      from 1994 to 2001 in the Department of Hematology and Pediatric Oncology in
      Wroclaw. All patients were qualified as the clinical stage III and treated with
      primary chemotherapy and/or radiotherapy, followed by total cystectomy and
      subsequent genitourinary reconstruction modo Studer. This procedure led in all
      cases to the complete remission, which is present up to date. The regular
      clinical and diagnostic controls as well as the patients' compliance enable the
      immediate detection of any possible complication as well as the nearly unchanged
      life activity.

PMID- 15559617
TI  - [Simple bone cyst].
AB  - The article describes up-to-date views on epidemiology, diagnosis and treatment
      simple bone cyst. It presented six cases of simple bone cyst treated in the
      Maxillofacial Surgery Division of Wojewodzki Szpital Specjalistyczny in Rzeszow.

PMID- 15559618
TI  - [Eosinophil apoptosis and asthma].
AB  - Eosinophils play an important role in airway inflammation in asthma. Eosinophils
      are believed through the release of their mediators to develop the irreversible
      structural airway changes. Dysregulation of apoptosis can lead to pathological
      accumulation of eosinophils in bronchial tissue. Apoptosis (programmed cell
      death) leads to the characteristic morphologic changes including reduction of the
      cellular volume, blebbing of the membrane, condensation of the nuclear chromatin,
      DNA laddering, mitochondrial dysregulation and finally to apoptotic bodies.
      Apoptosis can be induced by oncogenes, specific ligands and some cytokines. On
      the other hand IL-5, IL-3 and GM-CSF (granulocyte-macrophage-colony stimulating
      factor) dramatically increase the life span of eosinophils. Glucocorticoids
      promote eosinophil apoptosis and totally reverse the delayed death cased by beta2
      agonists.

PMID- 15559619
TI  - [Spondyloarthropathies in childhood].
AB  - In this paper the author presents the own and other authors' current opinions
      about the classification, pathophysiology, clinical picture, differential
      diagnosis, treatment and prognostic problems in the course of juvenile
      spondyloarthropathies.

PMID- 15559620
TI  - [Patients' beliefs about their illness and adaptation after myocardial
      infarction].
AB  - Patients' beliefs about their illness can significantly influence the course of
      treatment, rehabilitation and further adaptation to life after myocardial
      infarction (MI). According to model of Leventhal five elements of the illness
      representation are distinguished: beliefs about etiology of illness, its symptoms
      and label, the personal consequences of the illness, how long it will last, and
      the extent to which the illness is amenable to control or cure. There is some
      evidence that on the basis of these elements, it is possible, to some extent, to
      predict the course of recovery process, effectiveness of the rehabilitation, and
      return to social and occupational functioning. The doctors play very important
      role in shaping of illness representation and modifying this beliefs which are
      harmful from the perspective of treatment goals. In the same time, there are some
      limitations and difficulties in practice use of knowledge arising from presented
      studies. First, the doctors very seldom recognize the patients' beliefs about
      treatment and medical recommendations' acceptance. Second, in health threat
      situations often come to defensive distortions of information in ways that
      confirm preferred beliefs, which can be demonstrated as a minimization or
      avoidance of real threat.

PMID- 15559621
TI  - [Fournier's gangrene].
AB  - Fournier's gangrene is a necrotizing fasciitis of the genital and scrotal region
      due to infectious process. The gangrene is rare. Most cases are diagnosed in
      elderly patients with immunodeficiency, especially in diabetics or alcoholics.
      Currently a primary infection focus can be revealed in about 95% cases. The nidus
      is usually located in the genitourinary tract, lower gastrointestinal tract or
      skin. Fournier's gangrene is a mixed infection caused by both aerobic and
      anaerobic bacterial flora. The development and progression of the gangrene is
      often fulminating and can rapidly cause multiple organ failure and death. Early
      surgical debridement of necrotic tissues and antibiotics are fundamental in the
      treatment of Fournier's gangrene. Despite of advanced management mortality is
      still high and averages 20-30%.

PMID- 15559622
TI  - [Hepatocyte growth factor (HGF) and atherosclerosis].
AB  - Hepatocyte growth factor (HGF) takes part in tissue regeneration after injury. It
      is a potent survival and regeneration factor after severe tissue damage. It
      promotes cell growth and protection from apoptosis, regulates the cell migration
      and differentiation. HGF is a subject of intensive investigations in order to
      apply it in the future in gene therapy to improve treatment of angina pectoris or
      intermittent claudication. The aim of this review is discussion about the role of
      HGF in pathogenesis and treatment of atherosclerosis. Angiogenetic activity of
      HGF was proven in vivo as well as in vitro. In patients with collaterals
      increased HGF plasma concentration was revealed. It is possible to determine with
      high probability the risk of cardiovascular event on the basis of HGF
      concentration. Plasma concentration of this factor increases dramatically after
      heparin injection, particularly after unfractionated heparin. Also other drugs
      (ACE-inhibitors) may take part in regulation of HGF synthesis.

PMID- 15559623
TI  - [Caroli's disease--if so rare clinical problem?].
AB  - Jacques Caroli for the first time described in the year 1958, cavernous
      dilatation of the hepatic bile ducts. It's the rare abnormality; there have been
      reported less than 200 cases until now. The disease is caused by defects in the
      genetic program which are transmitted in an autosomal recessive way. There are
      two basic types of the disease: focal (so called. "simple type") and diffuse,
      embracing entire bile tree. Both types maybe associated with congenital hepatic
      fibrosis and then the abnormality is usually called "Grumbach disease". There is
      an excessive risk of cancer (cholangiocarcinoma) in patients with Caroli's
      disease. Dominant symptoms are due to recurrent cholangitis, sometimes with signs
      of portal hypertension. Basic treatment is hepatic resection (focal form) and
      internal bypass of the biliary tree (diffuse form). The prognosis of the disease
      is reserved one.

PMID- 15559624
TI  - [Patients' expectations for medical care--concepts, typology, research methods].
AB  - The article reviews literature concerning patients' expectations for medical
      care. The concept of expectations, typology and research methods are discussed.
      The author indicates the need for in-depth investigations to determine how
      patients define their expectations. Qualitative techniques are of help. The
      standardization of terminology will enable a comparison of patients' expectations
      in Poland with patients' expectations in other countries.

PMID- 15559625
TI  - [Pharmacological correction of memory impairment caused by a complex extremal
      action in mice with bilateral ligation of common carotid arteries].
AB  - Semax and mexidol significantly increase the survival of white mongrel male mice
      upon bilateral ligation of common carotid arteries. Semax virtually completely
      prevented retrograde amnesia development in ligated mice under conditions of a
      complex extremal action (emaciating swim in cold water with simultaneous wheel
      rotation) and increased the lifetime of these animals in altitude test chamber.

PMID- 15559626
TI  - [Antiamnesic effect of cytoflavin and neuronol in rats with ischemic impairment
      of cerebral circulation].
AB  - The antiamnesic action of the new complex preparations cytoflavin and neuronol
      was studied in rats with a cerebral ischemia model, tested for the passive
      avoidance conditioned reflex. The neuroprotector effect of drugs was determined
      by morphological methods. Both cytoflavin and neuronol reduced neuronal damage in
      the pyramidal layer of the hippocampus and prevented the development of amnesia
      during the entire period of cerebral ischemia (3-21 days). Both drugs also
      improved horizontal locomotor activity and emotional reactions of animals in the
      open field test.

PMID- 15559627
TI  - [Afobazole increases cerebral blood flow in rats with global brain ischemia].
AB  - The selective anxiolytic drug afobazole administered in a dose of 5 mg/kg
      increased the cerebral blood flow in rats. The effect was more pronounced in rats
      with global reversible cerebral ischemia than in intact animals. The ischemia
      model was caused by occlusion of both common carotid arteries for 120 min with
      simultaneous reduction of the arterial pressure to 40-50 mm Hg through blood
      letting. Afobazole also significantly increased the survival of rats with
      cerebral ischemia model caused by ligation of both common carotid arteries, which
      was evidence of the neuroprotector activity. Apparently, the ability of afobazole
      to improve the cerebral blood flow in ischemized rat brain is an important factor
      in realization of the neuroprotector activity.

PMID- 15559628
TI  - [Neuroprotector action of an asparagic acid derivative during the model
      reperfusive cerebral damage in cats].
AB  - Neuroprotector properties of a new phosphorylated derivative of asparagic acid
      (PIR 87-65-0) were studied on a model of acute brain ischemia in cats. PIR 87-5-0
      has proved to be more effective than the reference drug vinpocetin in preventing
      the reperfusive damage, which was manifested by decreased postischemic
      hypergycemia, activated utilization of oxygen and glucose in the brain, and
      suppressed postischemic metabolic lactate acidosis.

PMID- 15559629
TI  - [Activation of the sympathetic nervous system influences the antifibrillatory
      effect of class I antiarrhythmic drugs].
AB  - The experiments with anesthetized rats showed that drugs belonging to various
      subclasses of class I antiarrhytmic agents (novocainamide, IA; lidocaine, IB;
      ethacizine, IC) produce a pronounced antifibrillatory and antiarrhythmic action
      under the conditions of a 7-min occlusion followed by reperfusion of the anterior
      descending branch of the left coronary artery. In the arrhythmia model with beta
      adrenoreceptors stimulated by isoproterenol, novocainamide (IA) and lidocaine
      (IB) retained their efficacy, in contrast to ethacizine (IC). This difference in
      the behavior of antiarrhythmic drugs may be related to their different
      antiarrhythmogenic potentials.

PMID- 15559630
TI  - [Antiaggregant and antioxidant activity of estradiol and tamoxifen].
AB  - Tamoxifen did not influence the human platelet aggregation in vitro, while
      estradiol at a concentration of 10(-6) M inhibited the aggregation of human
      thrombocytes induced by ADP, serotonin + adrenaline, and adrenaline (epinephrine)
      by 14.7, 12.5, and 16.6%, respectively. Estradiol introduced in the range of
      effective concentrations from 10(-8) to 10(-4) M inhibited lipid peroxidation,
      while tamoxifen produced this effect only at a concentration of 10(-4) M. There
      was a correlation between the antiaggregant activity and antioxidant properties
      of estradiol.

PMID- 15559631
TI  - [Essentiale and riboxin induce immunomodulant activity of erythrocyte stroma in
      rats with toxic anemia and in intact animals].
AB  - The stroma of red blood cells in rats injected with riboxin after extracorporal
      treatment with essentiale acquired immunomodulant properties, with a significant
      increase in Mg2+ -ATPase activity. Light erythrocytes producing immunosuppressing
      action appeared in the blood of animals poisoned with phenylhydrazine or sodium
      nitrite. Introduction of hemotropic poisons reduced the activity of Mg2+ -ATPase
      in the stroma. Riboxin injections in poisoned animals, followed by essentiale
      treatment of the stroma induced immunostimulating properties and normalized Mg2+ 
      ATPase activity of erythrocyte membranes.

PMID- 15559632
TI  - [The effect of immunofan on the immunity system characteristics and lipid
      peroxidation parameters upon acute chemical poisoning].
AB  - The results of experiments on Wistar rats under conditions of acute poisoning
      with 0.75 LD50 of zarin (isopropylmethyl fluorophosphonate), luisite (beta
      chlorovinyl dichloroarsine), arsenic chloride, and dichloroethane showed that a
      four-day treatment with immunofan in a dose of 10 microg/kg restored the immune
      status characteristics (antibody formation to T-dependent antigen, antibody
      dependent cell-mediated cytotoxicity, natural killer cell activity, and delayed
      type hypersensitivity) and the related LPO parameters.

PMID- 15559633
TI  - [Immunopharmacological activity of xymedone in patients with atopic bronchial
      asthma].
AB  - Xymedone produced therapeutic effect in patients with atopic bronchial asthma.
      The drug action was manifested by a decrease in the IgE level and an increase in
      gamma-interferon level. Adding xymedone to lymphocytes cultivated with
      phytohemagglutinin revealed stimulating action of this drug on the delayed-type
      hypersensitivity. Mechanisms involved in the immunotropic action of xymedone are
      discussed.

PMID- 15559634
TI  - [The effect of ladasten on the activation-induced expression of Fas receptor on T
      lymphocytes and their sensitivity to Fas-induced apoptosis].
AB  - The effects of ladasten on the activation-induced expression of Fas-receptor on T
      lymphocytes, their sensitivity to Fas-induced apoptosis, and the expression of
      mitogen-activated ERKI/ERK2 protein kinases have been studied. In the range of
      concentrations 0.1-10 microM, ladasten exhibited a comitogenic effect on the TCR
      mediated stimulation of T-lymhocytes ion the peripheral human blood, which was
      accompanied by an increase in the level of phosphorylated form of ERK-2. At the
      same time, ladasten virtually did not change the activation-induced expression of
      Fas-receptor on T-lymphocytes, but reduced the rate of the Fas-induced apoptosis.
      It was concluded that the immunoprotective effect of ladasten is probably based
      on a decrease in the rate of Fas-induced apoptosis.

PMID- 15559635
TI  - [The effect of antitumor polychemotherapy on the structural, metabolic, and
      functional status of erythrocytes in patients with head and neck tumors].
AB  - The structure, metabolic status, and functional properties of erythrocytes in
      patients with stage III-IV head and neck tumors in the course of antineoplastic
      cytostatic chemotherapy (platidiam, 5-fluorouracil, methotrexate) were studied.
      In the course of this treatment, disorders of the morphology and functional state
      of erythrocytes (reduced dry mass, decreased content of sulfohydryl grups and
      lipoproteins, increased number of transformed cells and the cells with violated
      ultrastructure, enhanced reversible aggregation of erythrocytes) were retained or
      became more pronounced.

PMID- 15559636
TI  - [Toxicological characterization of calcium ketopantoylaminobutyrate].
AB  - The investigation of toxicity of calcium ketopantoylaminobutyrate (Ca-KPAB)
      showed that this newly synthesized compound belongs to the class of low-toxicity
      substances. The LD 50 of Ca-KPAB for oral administration is lower than that of
      pantogam. No toxicity manifestations and local irritant activity was observed
      upon chronic administration of Ca-KPAB. The therapeutic index of Ca-KPAB is more
      than 17 times that of pantogam.

PMID- 15559637
TI  - [Multiparametric analysis of the effect of ethanol in various doses on EEG in
      rats].
AB  - Multiparametric EEG analysis (840 parameters) was performed for 24 points over
      the entire dorsal cerebral cortex in outbred rats intraperitoneally injected with
      ethanol in low (0.75 g/kg), medium (2.0 g/kg), and high subnarcotic (4.5 g/kg)
      doses. Acute intoxication with low ethanol doses led to an increase in the
      spectral power and coherence in the frequency band of the dominating theta-rhythm
      peak (5.75-7.25 Hz), which was indicative of activation of the septo-hippocampal
      system (with improvement of the related functions such as attention, memory, and
      exploratory activity). The coherence was also increased in several high-frequency
      bands of the EEG alpha- and beta-rhythm. Ethanol administered in medium and high
      doses produced a shift of the dominating theta-rhythm peak to lower frequencies
      (4.50-5.75 Hz), which was evidence of reduced activity of the septo-hippocampal
      system and the related CNS functions. These doses of ethanol significantly
      decreased the spectral power and coherence in most of the high-frequency bands of
      the EEG alpha- and beta-rhythm, which can be explained by reduced energy and
      synaptic activity of the cortex leading to impaired high brain functions and the
      development of somnolent and narcotic effects. Using special sets of reliably
      modified parameters and a special algorithm, it is possible to solve the inverse
      problem of identifying experiments (EEG fragments) corresponding to low, medium,
      and high doses of ethanol.

PMID- 15559638
TI  - [Substantiation of the use of L-carnitine for the treatment of alcoholism].
AB  - Available experimental and clinical data on the role of the L-carnitine system in
      the organism of mammals in the state of alcohol intoxication are summarized.
      Possible mechanisms of the protective action of L-carnitine in cases of alcohol
      injury are considered.

PMID- 15559639
TI  - [Experimental and clinical evaluation of the efficacy of ecdysten in the
      treatment of hepatitis].
AB  - The properties of ecdysten, an exdysterone-based preparation, were studied under
      experimental (of heliotrine induced hepatitis model in rats) and clinical
      (chronic viral hepatitis B) conditions. A 2-week treatment with ecdysten in a
      daily dose of 5 mg/kg (p.o.) significantly improved the state of rat liver, as
      manifested by normalization of the enzymatic activity of blood serum, stimulation
      of the protein and glycogen synthesis, inhibition of lipid peroxidation, and
      activation of all chains of microsomal oxidation of hepatocytes. The inclusion of
      ecdysten into a complex therapy scheme for patients with chronic viral hepatitis
      B (5-mg tablets twice per day over a period of 30 days) substantially improved
      the clinical and biochemical indices of the functional state of liver, positively
      influenced the humoral and cell immunity and the resistance factors, and
      normalized the course of autoimmune processes accompanying the liver pathology.

PMID- 15559640
TI  - [The effect of cytomedines on the hemostatic and antioxidant potential of
      patients in the early stage of diabetic retinopathy].
AB  - Epithalamine produces a dose-dependent antioxidant effect in patients in the
      early stage of diabetic retinopathy (DR). Retinalamine normalizes the parameters
      of local hemostatic potential only under the conditions of completely restored
      antioxidant activity and lipid hydroperoxide level. Combined administration of
      epithalamine and retinalamine is recommended for correcting pathological changes
      of the hemostatic and antioxidant potential and for preventing the blood vessel
      damage in patients in the early stage of DR.

PMID- 15559641
TI  - [Oxymethyluracil stimulates reparative regeneration of skin in rats].
AB  - Oxymethyluracil (OMU) ointment stimulated reparative regeneration of skin in
      white mongrel rats with model skin damage. The efficacy of this preparation is
      higher than that of methyluracil-containing ointments (especially of the gel
      based preparation). Simultaneous oral administration of OMU potentiated the
      efficacy of the ointment. After oral administratrion, OMU was found in the wound
      OMU decreases the level of malonic aldehyde in the blood of rats with model
      wounds, while not changing the level of nitrogen oxide. In the test group treated
      with OMU ointment, the biomechanical characteristics of cicatrix after wound
      healing are closer to the characteristics of intact skin than in the untreated
      control group.

PMID- 15559642
TI  - [The effect of curiozin gel and adhesive plaster application on the healing and
      blood flow dynamics in skin autografts from various areas of body in rats].
AB  - The stimulating effect of curiozin gel and plaster application on the engraftment
      of skin autografts from various areas of body was studied in rats. Curiozin gel
      in a single dose of 75 mg was used for the daily treatment of autografts over the
      entire postoperation period of time. The adhesive plaster was applied onto skin
      autografts for 5 days after skin transplantation. The skin autografts in the test
      group exhibited normalized volume blood flow dynamics, reduced duration of the
      inflammatory reaction, and improved the quality of engraftment as compared to the
      untreated control group. The best healing and blood-flow-normalizing effect was
      achieved by combined application of curiozin gel and adhesive plaster.

PMID- 15559643
TI  - [The role of immunological factor in pharmacology of anxiolytic drugs and
      antidepressants].
AB  - Emotional stress and mental depression are accompanied by disturbances of the
      immune state in both humans and experimental animals. Administration of
      anxiolytic drugs and antidepressants allows these immunological shifts to be
      corrected. This effect may be a component of the specific psychotropic activity
      of such drugs.

PMID- 15559645
TI  - An infrastructure model for the implementation of VISION 2020: the right to
      sight.

PMID- 15559646
TI  - Foldable acrylic versus rigid polymethylmethacrylate intraocular lens in combined
      phacoemulsification and trabeculectomy.
AB  - BACKGROUND: Combined trabeculectomy and phacoemulsification is a widely accepted
      option in treating patients with glaucoma who also have cataracts. Implantation
      of a foldable intraocular lens (IOL) in cataract surgery has several theoretical
      advantages. We performed a study to determine the results of combined
      phacoemulsification and trabeculectomy with mitomycin C and implantation of
      either a foldable acrylic or rigid polymethylmethacrylate (PMMA) IOL. METHODS:
      Review of the charts of 58 consecutive patients (60 eyes) who underwent combined
      phacotrabeculectomy for concomitant cataract and glaucoma at a university
      affiliated hospital in Montreal between September 2001 and December 2002. Forty
      one eyes received a foldable acrylic lens (3.2-mm-wide incision), and 19 eyes
      received a rigid PMMA lens (5.2-mm-wide incision). Outcome measures included
      visual acuity, intraocular pressure (IOP) and postoperative complications. The
      results in the two groups were compared. RESULTS: There were no differences in
      baseline characteristics between the two groups. Earlier recovery of visual
      acuity was noted in the foldable IOL group than in the rigid IOL group (p = 0.013
      for the difference at day 7). IOP control was similar in the two groups, as was
      the incidence of IOP spikes in the early postoperative period. INTERPRETATION:
      The results suggest that combined phacotrabeculectomy with mitomycin C using a
      foldable acrylic IOL allows for good postoperative IOP control and earlier visual
      recovery than the same procedure with insertion of a rigid PMMA lens.

PMID- 15559647
TI  - Juvenile arthritis-associated uveitis: visual outcomes and prognosis.
AB  - BACKGROUND: The current issues in the management of uveitis associated with
      juvenile arthritis revolve mainly around the treatment of mild disease and how to
      treat patients with more severe disease. The aims of this study were to determine
      the incidence of uveitis in a cohort of patients with juvenile arthritis as well
      as the nature of treatment and the risk factors for visual loss. METHODS: Review
      of the charts of 71 patients with juvenile arthritis, as defined by the American
      Academy of Rheumatology, seen between 1992 and 2001 at a combined rheumatology
      and ophthalmology clinic. Information collected included the patient's sex, age
      at diagnosis of arthritis and uveitis, and date of diagnosis of arthritis and
      uveitis. The rheumatologic diagnosis, results of serologic testing, and details
      of systemic and topical treatments were also recorded. RESULTS: There were 47
      girls and 24 boys ranging in age from 16 months to 13 years. The median age at
      diagnosis of juvenile arthritis was 4 years and 1 month. Twenty-seven patients
      (38%) had uveitis. The median age at uveitis onset was 5.9 years, with an average
      interval of 18 months from the diagnosis of arthritis; 11 patients had uveitis at
      the time of arthritis diagnosis. There was a positive relation between anti
      nuclear antibody positivity and the development of uveitis (p < 0.05). Thirteen
      (48%) of the 27 patients with uveitis had mild anterior segment inflammation,
      with fewer than 25 cells in the anterior chamber. This group had spontaneous
      resolution of uveitis without topical therapy. All the patients without uveitis
      had a final visual acuity of 6/9 or better. Five of the patients with uveitis had
      a final visual acuity of 6/36 or worse. Cataract was the most common complication
      affecting visual outcome. Cataract extraction initially improved the visual
      acuity, but posterior segment complications and glaucoma compromised the final
      visual outcome. INTERPRETATION: We found an incidence of uveitis of 38% with long
      term follow-up of patients with juvenile arthritis; the uveitis was diagnosed an
      average of 18 months after the arthritis. Almost half of the patients with
      uveitis had minor anterior segment inflammation. These patients did not receive
      topical treatment and had good visual outcomes. Patients with uveitis at the time
      of diagnosis of arthritis tended to have a worse visual prognosis and experienced
      persistent uveitis despite treatment. In this series, cataract extraction was
      beneficial in improving visual acuity immediately postoperatively, but posterior
      segment changes and glaucoma may compromise final visual outcomes.

PMID- 15559648
TI  - [Amniotic membrane transplantation for the treatment severe acanthamoeba
      keratitis].
AB  - BACKGROUND: It is now possible to treat ocular surface disorders by means of
      amniotic membrane transplantation. We performed a study to determine the efficacy
      of this technique in the treatment of severe Acanthamoeba keratitis. METHODS: We
      studied six patients with severe, painful, nonhealing Acanthamoeba keratitis who
      underwent one or two amniotic membrane transplantation procedures between
      February 2001 and January 2003. Histopathological analysis of the corneal buttons
      was performed in four cases. RESULTS: Eight amniotic membrane transplantation
      procedures were performed. The mean length of follow-up was 14 (range 3-21)
      months. The mean interval between institution of medical treatment and the
      procedure was 3.6 months. All patients had progressive stromal lesions caused by
      an inflammatory reaction. Complete reepithelialization occurred in four cases,
      and partial healing in two cases. Ocular inflammation and tissue destruction were
      decreased in all cases, pain was lessened in five cases, and corneal
      neovascularization was decreased in four cases. No postoperative complications
      were observed. Amniotic membrane was observed under dysplastic corneal epithelium
      on histologic examination. INTERPRETATION: Amniotic membrane transplantation may
      be a safe and effective treatment of severe Acanthamoeba keratitis, particularly
      during the inflammation phase. It may permit penetrating keratoplasty to be
      delayed.

PMID- 15559649
TI  - Ocular and nonocular findings in patients with aniridia.
AB  - BACKGROUND: Aniridia typically appears as a familial condition with autosomal
      dominant inheritance but can present as an isolated disease or sporadically in
      association with several syndromes. In this report we describe the various ocular
      manifestations of aniridia as well as the association of familial aniridia with
      two different ocular and systemic abnormalities present across three generations
      in two different families. METHODS: Descriptive case series of 33 patients (66
      eyes) with aniridia. A full eye examination was performed at the beginning of the
      study, including past medical history, family history and type of inheritance,
      assessment for fixation pattern and presence of nystagmus, visual acuity testing,
      refraction, slit-lamp examination, gonioscopy, fundus examination with pupil
      dilation and anterior segment photography; additional glaucoma testing was done
      if the patient had high intraocular pressure. Patients were followed for at least
      2 years. The interval between follow-up visits, which included gonioscopy and
      fundus examination with pupil dilation, depended on the findings in each case. A
      urology consultation was requested in all sporadic aniridia cases; consultations
      in psychiatry and gynecology were requested on the basis of the medical history
      or clinical suspicion during the ophthalmologic examination. RESULTS: Ten
      patients (30%) had sporadic aniridia, with no previous family history; Wilms'
      tumour did not develop in any of them during the follow-up period. In the
      autosomal dominant group, ocular and systemic findings present in combination
      with aniridia were observed in 20 patients in the two families. Family I had
      aniridia and developmental delay or behavioural disorders in three generations as
      well as high myopia (greater than 6.00 dioptres) in all affected adults. Family 2
      presented a wide phenotypic variability of aniridia with myopia in three
      generations. Open-angle glaucoma developed in three young adults in this family,
      and two members were found to have gynecologic abnormalities (hypoplastic uterus
      and imperforate vagina). Myopia was the most prevalent refractive error (64%) in
      the 33 patients. Refractive correction significantly improved the visual acuity
      in half of these cases. Glaucoma was present in 10 patients (30%) and was the
      main cause of vision loss, provoking blindness in two cases (6%). Affected
      patients manifested progressive angle closure or presented with open-angle
      glaucoma. INTERPRETATION: Ophthalmologists should consider aniridia in patients
      with unusual iris malformations. Examination of family members may be key in
      making the diagnosis. Any refractive error should be corrected, as this may
      improve vision. All aniridic patients should be screened regularly for glaucoma,
      as this condition may occur at any age and can lead to permanent vision loss.
      Systemic and ocular associations should be considered as they may present in
      combination with anirida. In our series, developmental delay or behavioural
      disorders and myopia were associated conditions.

PMID- 15559650
TI  - Surgery and botulinum toxin in congenital esotropia.
AB  - BACKGROUND: In a previous study we investigated the advantages and drawbacks of
      early and delayed injection of botulinum toxin as primary treatment of infantile
      esotropia with nystagmus in abduction (IENA). We carried out a further study to
      investigate the role and efficacy of surgery in this condition and to determine
      the possible effect of previous injection of both medial recti with botulinum
      toxin in patients requiring a final horizontal surgical correction. METHODS:
      Review of the records of 44 patients (24 girls and 20 boys) with IENA seen
      between 1979 and 1998 who had undergone at least one horizontal surgical
      procedure. The outcomes in the 16 patients who had previously received botulinum
      toxin were compared with those in the 28 patients for whom surgery was the
      primary treatment. RESULTS: There was a negative correlation between the
      pretreatment esotropic angle and age (Pearson's r = -0.45, p < 0.05). The first
      visit to a surgical specialist took place very late (mean age 43 months [standard
      deviation (SD) 39 months]). Of the 35 children seen during the period in which
      botulinum toxin was available, 20 (57%) had additional factors inducing
      unsteadiness of binocular vision (e.g., moderate to severe initial relative
      amblyopia, initial ametropia). Administration of 5 units of botulinum toxin
      before 18 months of age destabilized dissociated vertical deviation. Overall, 39
      patients (89%) had a final residual deviation of less than 10 prism dioptres. The
      first surgical correction was horizontal and vertical-torsional in 30 patients
      (68%). A total of 23 patients (52%) required some retreatment (botulinum toxin or
      surgery or both). Children treated initially with botulinum toxin had less
      surgery than those with initial surgery (mean recession or resection 8.9 mm [SD
      4.5 mm] vs. 14.2 mm [SD 4.0 mm]) as well as fewer horizontal muscles operated
      (mean 1.6 [SD 0.6] vs. 2.3 [SD 0.6]). INTERPRETATION: Surgery with or without
      further interventions is a reasonable approach for IENA with delayed diagnosis
      and in cases associated with unsteadiness of binocular vision or with
      nonhorizontal deviations. Initial treatment with botulinum toxin, injected into
      both medial recti, is effective, reducing the amount of further horizontal
      surgery and favouring postoperative stability, except in children under 18
      months, in whom injection of 5 units induces unbalanced dissociated vertical
      deviation.

PMID- 15559651
TI  - Modified retractor plication technique in lower lid entropion repair: a 4-year
      follow-up study.
AB  - BACKGROUND: Lower eyelid entropion is an eyelid malposition characterized by
      inward rotation of the eyelid margin associated with potentially significant
      discomfort and, occasionally, keratopathy. In this study we evaluated and
      compared the efficacy of two surgical techniques of retractor plication for
      involutional lower lid entropion repair. METHODS: Sixty-two consecutive patients
      (62 eyes) with involutional lower lid entropion were included. Of the 62, 34
      underwent the Jones retractor plication technique, and 28 underwent a
      modification of this technique that simplifies the procedure. We evaluated
      horizontal lid laxity, medial canthal tendon laxity and lower lid excursion
      before and after surgery, and determined the rate of entropion recurrence in the
      two groups. All measures were obtained before and 1 month, 6 months, 1 year, 2
      years, 3 years and 4 years after surgery. RESULTS: Preoperatively, there was no
      statistically significant difference between the two groups in any of the
      measures studied. Postoperatively, the mean amount of horizontal lid laxity was
      significantly less in the modified technique group than in the Jones technique
      group (6.86 mm [standard deviation (SD) 0.41 mm] vs. 7.30 mm [SD 0.64 mm]) (p <
      0.05). Similarly, the mean amount of medial canthal tendon laxity in the resting
      position was significantly less in the modified technique group than in the Jones
      technique group (1.90 mm [SD 0.56 mm] vs. 1.25 mm [SD 0.43 mm]) (p < 0.05). The
      rate of entropion recurrence was significantly lower in the modified technique
      group (7.1%) than in the Jones technique group (14.7%) (p < 0.05).
      INTERPRETATION: The modified retractor plication technique showed encouraging
      results in terms of successful and long-lasting lower lid entropion repair.

PMID- 15559652
TI  - The utility of multifocal electroretinography in monitoring drug toxicity:
      deferoxamine retinopathy.

PMID- 15559653
TI  - [Multiple astrocytic hamartomas in the bilateral retina].

PMID- 15559654
TI  - Familial HLA-A2- and HLA-B7-associated anterior uveitis.

PMID- 15559655
TI  - Vitritis as the primary manifestation of graft-versus-host disease: a case report
      with vitreous cytopathology.

PMID- 15559656
TI  - Acute intractable glaucoma after a single low-dose sub-Tenon's corticosteroid
      injection for macular edema.

PMID- 15559657
TI  - Infantile glaucoma in a patient with Rothmund-Thomson syndrome.

PMID- 15559659
TI  - Kentucky court wrestles with scope of consent. Hoofnel v. Segal.

PMID- 15559658
TI  - Adenocarcinoma of the eyelid as the presenting sign of breast carcinoma.

PMID- 15559660
TI  - Physician Network joint venture permanently dissolved.

PMID- 15559661
TI  - Election 2004: health care is the loser.

PMID- 15559662
TI  - ICD-10: capturing the complexes of health care.

PMID- 15559663
TI  - Consumer-driven health plans: implications for providers.
AB  - By shifting more healthcare costs to workers, employers are hoping to slow the
      rise in company costs. It is too early to tell whether these consumer-driven
      health plans will address the issue of soaring costs. However, one thing is
      certain: They will have ramifications for healthcare providers.

PMID- 15559664
TI  - Are you of good report?
AB  - Past Medicare credit balance reports may come back to haunt you as current
      federal enforcement activities indicate they could easily fall under False Claims
      Act scrutiny.

PMID- 15559665
TI  - Joint resolution blending finance and strategy.
AB  - When strategic planning and financial planning are disconnected processes,
      healthcare organizations can rarely accomplish the integrated, analysis-based
      decision making that ensures long-term access to capital. CFOs need to be
      actively involved in an integrated planning approach to ensure its success.

PMID- 15559666
TI  - Effective demand forecasting in 9 steps.
AB  - Effective forecasting of demand for healthcare services requires nine steps: 1.
      Assemble historical data. 2. Analyze historical trends. 3. Identify key demand
      drivers. 4. Identify relevant benchmarks. 5. Model existing conditions. 6.
      Develop core assumptions for population-based demand. 7. Develop core assumptions
      for provider-level demand. 8. Create a baseline forecast of future demand. 9.
      Test sensitivity of projections to changes in core assumptions.

PMID- 15559667
TI  - Strategic business planning linking strategy with financial reality.
AB  - To succeed in today's complex and often adverse business environment, a
      healthcare organization's strategic direction must be calculated, focused, and
      financially sustainable. Strategic business planning is an essential tool to help
      organizations focus strategic choices within the financial realities of their
      environment. An effective strategic business planning cycle includes conducting
      an assessment, identifying business objectives, developing strategy, conducting
      an impact analysis, and developing an implementation plan.

PMID- 15559668
TI  - 7 steps for evaluating primary care practice ownership.
AB  - Hospitals shouldn't dismiss a primary care practice ownership strategy from the
      outset. Instead, it's important to learn from past missteps and conduct a
      thorough analysis of the opportunity by focusing on population growth and
      demographics, hospital utilization rates, disease and illness rates, physician
      supply and demand, market share, case-mix index, other hospital-owned physician
      practices, and concerns pertinent to the potential development site.

PMID- 15559669
TI  - The business case for better buildings.
AB  - Beginning in 2000, a research collaborative of progressive healthcare
      organizations came together with The Center for Health Design to evaluate the
      impact of their new buildings on patient outcomes. Those organizations are now
      engaged in three-year programs of evaluation, using comparative research
      instruments and outcome measures. Their experiences are synthesized here in a
      composite 300-bed "Fable Hospital" to present evidence in support of the business
      case for better buildings as a key component of better, safer, and less wasteful
      health care.

PMID- 15559670
TI  - New reimbursement models reward clinical excellence.
AB  - Pay-for-performance is an emerging payment model that links quality of care with
      the level of payment for healthcare services. While pay-for-performance programs
      are still in their formative stages, hospitals need to prepare by intensifying
      their efforts to ensure systems and processes support high-quality care.

PMID- 15559671
TI  - Key strategies for sustained performance improvement.

PMID- 15559672
TI  - Reinventing yourself: every day.

PMID- 15559673
TI  - Aiming for more than a base HIT.
AB  - To position themselves for optimal use of health information technology through
      goals such as electronic health records and the eventual transition to a national
      health information infrastructure, providers need to make better decisions
      regarding the use of their existing systems.

PMID- 15559674
TI  - Signed, screened, and delivered.

PMID- 15559675
TI  - An unusual capital source for rural hospitals: agriculture.

PMID- 15559676
TI  - California patient care labor costs rise under staffing requirements.

PMID- 15559677
TI  - Club drugs: reasons for and consequences of use.
AB  - This preliminary descriptive study was designed to assess the reasons, primary
      contexts, and consequences (physical, psychological, lifestyle) of club drug use
      in a sample of young adults in a mid-size U.S. city. Fifty young adults (18 to 30
      years old) reported on their use of club drugs (Ecstasy, GHB, ketamine, Rohypnol,
      methamphetamine, LSD) in face-to-face interviews that included quantitative and
      qualitative measures. Ecstasy was the most frequently used club drug followed by
      ketamine, LSD and methamphetamine. All of the participants reported using club
      drugs to "experiment" and most reported using these drugs to feel good and
      enhance social activities. Club drugs were frequently used at raves, in bars or
      clubs, and at home with friends. An average of 16 negative physical,
      psychological, and lifestyle consequences were reported for club drug use.
      Despite substantial negative consequences, participants perceived several
      positive consequences of regular recreational club drug use. These findings
      corroborate descriptions of club drug use in other countries (e.g., Australia,
      United Kingdom) and provide additional information on perceived positive
      consequences that users experience with club drug use. Further exploration of the
      reasons and positive consequences that are associated with use of each of the
      club drugs may provide important information on the growing trend in use of these
      drugs.

PMID- 15559678
TI  - Acute toxic effects of club drugs.
AB  - This article summarizes the short-term physiological toxicity and the adverse
      behavioral effects of four substances (GHB, ketamine, MDMA, and Rohypnol) that
      have been used at latenight dance clubs. The two primary data sources were case
      studies of human fatalities and experimental studies with laboratory animals. A
      safety ratio was calculated for each substance based on its estimated lethal dose
      and its customary recreational dose. GHB (gamma-hydroxybutyrate) appears to be
      the most physiologically toxic; Rohypnol (flunitrazepam) appears to be the least
      physiologically toxic. The single most risk-producing behavior of club drug users
      is combining psychoactive substances, usually involving alcohol. Hazardous drug
      use sequelae such as accidents, aggressive behavior, and addiction were not
      factored into the safety ratio estimates.

PMID- 15559679
TI  - Crack cocaine and sex.
AB  - The impact of crack cocaine use on number of sex partners was examined using
      bivariate analyses and a logistic model on a national treatment cohort of 4939
      individuals. Number of sex partners over the last 12 months was dichotomized as
      none/one versus multiple partners for the logistic analyses. The model included
      11 independent variables not including prostitution or use of crack cocaine. For
      both genders, the bivariate analyses showed significant positive associations
      between crack use and number of partners regardless of type of sexual activity;
      those who used crack had more partners for all sexual activities queried,
      compared to those who did not. Cocaine, whether in powder or crack form, was
      positively associated with prostitution for both genders. For men the odds ratio
      for crack cocaine use ranged from 1.6 (heterosexual anal) to 5.5 (homosexual
      anal) and for women from 2.9 (heterosexual oral) to 4.1 (homosexual oral). If
      prostitution is added to the model the odds ratios are reduced for homosexual
      activities for men and reduced dramatically for all types of sexual activity for
      women.

PMID- 15559680
TI  - Stage model of recovery for chemically dependent adolescents: part 1--methods and
      model.
AB  - This qualitative study, presented in two parts, refines the model of how
      chemically dependent adolescents initiate and engage in the recovery process.
      Part 1 describes the research process and results used to derive the model. The
      model was derived from theory grounded in verbatim reports of 30 chemically
      dependent participants who first attempted recovery from chemical dependence
      during adolescence. The constant comparative method of grounded theory was used
      to analyze the data. This stage model of adolescent recovery includes the
      using/precontemplation, transition, early recovery, and ongoing recovery stages;
      the transition stage is divided into contemplation and action phases. The stages,
      phases, and significant events are similar, but not identical to, those presented
      in adult-based models of recovery from chemical dependence. In Part 2, the
      resulting theory is compared with extant theories on stages of recovery in
      chemically dependent adults, treatment implications for the adolescent population
      are reviewed, and topics for further research are suggested.

PMID- 15559681
TI  - Severely mentally ill consumers' perspectives on drug use.
AB  - Substance use disorders have serious negative consequences for severely mentally
      ill (SMI) adults, but many do not receive adequate substance abuse treatment. As
      part of a larger project on access barriers to substance abuse treatment for SMI
      clients, this qualitative study examined two potential client-level barriers to
      treatment: minimization of drug problems and perceived acceptability of drug use
      to reduce psychiatric symptoms. Open-ended interviews about drug use were
      conducted with 24 SMI adults with substance use problems. The majority of
      respondents identified drug use as a major problem in their lives. Respondents
      were aware of the impact of drugs on psychiatric symptoms, and most believed that
      the negative effects of drug use outweighed any short-term benefits. Nearly all
      respondents believed it was not acceptable for SMI adults to use drugs except
      marijuana. Contrary to findings in the literature that SMI adults deny or
      minimize drug problems, most respondents acknowledged the seriousness of their
      drug use, were aware of the negative effects of drug use on their psychiatric
      symptoms, and endorsed abstinence as the optimal treatment goal. These findings
      have implications for substance abuse treatment for SMI clients, particularly
      interventions that emphasize education about drug use as a way to increase
      motivation for treatment.

PMID- 15559682
TI  - "When you're using gear you put HIV to the back of your mind and forget about
      it": constructs of risk.
AB  - This article presents findings from a qualitative study concerning drug
      injectors' constructs of human immunodeficiency virus (HIV) risk behavior.
      Analysis of data obtained from in-depth interviews (some with a vignette) of drug
      injectors found that when individuals needed an injection of drugs and were
      experiencing drug withdrawal they were more likely to take drug injecting risks.
      This was often discussed within an overall preoccupation with drug use. The
      substantive focus of the analysis goes on to explore drug injectors' desire to
      think about the consequences of HIV risk behavior at a later point in time. These
      exploratory findings highlight how further research needs to be undertaken in
      order to improve understanding of the temporal issues concerning drug injecting
      HIV risk behavior.

PMID- 15559683
TI  - A qualitative exploration of the impact of cultural and social factors on heroin
      use in Shetland (Scotland).
AB  - In order to gain a greater understanding of the impact of social and cultural
      factors on patterns of heroin use and use-related behaviors, in-depth interviews
      were carried out with 12 heroin users in Shetland. Analysis revealed the
      existence of a small, highly organized and highly covert heroin subculture.
      Within this group, users were predominantly older, and their use was reported as
      being relatively self-controlled and unproblematic in nature, especially by
      comparison to the heroin use associated with deprived urban areas. There were
      indicators, however, that this situation seemed to have entered a phase of
      change, reflected by descriptions of an increasing number of younger, less
      controlled heroin users. Within the theoretical framework of drug, set and
      setting, the importance of drug-using norms and rules among heroin users in both
      regulating and maintaining patterns of use, even through periods of change, was
      identified. Shetland, with its relative affluence, small size and geographical
      isolation constitutes an unusual setting for research into heroin use, which
      customarily has been viewed as an urban phenomenon. Thus it offers the
      opportunity to gain insight into the nature of heroin use and associated
      behaviors from a relatively novel perspective.

PMID- 15559684
TI  - Perspectives on the drug court model across systems: a process evaluation.
AB  - Drug courts have been in existence since 1989, yet few process evaluations have
      appeared in the literature to help inform the discussion about their
      effectiveness. This article reports findings from a process evaluation of a drug
      court program in San Mateo, California. The evaluation was designed to document
      the history of the program, to examine program strengths and areas of
      improvement, to assess the roles and relationships among the various agencies
      involved and to describe the impact of the drug court on the justice and drug
      treatment systems. Methods included review of available drug court program
      documents, interviews with key stakeholders, and focus groups with drug court
      participants. The main findings were: support for the continuation of drug court,
      enhanced collaboration among all agencies, and an increased awareness of the
      needs of substance-using clients in the criminal justice system. Potential
      lessons for other drug courts include the importance of building strong
      collaborations and maintaining good communication, recognizing competing
      interests in developing procedures for drug court, and considering changes in
      eligibility criteria as experience with the drug court model expands.

PMID- 15559685
TI  - Treatment motivation and therapeutic engagement in prison-based substance use
      treatment.
AB  - Studies of community-based substance use treatment show that motivation for
      treatment is critical for clients becoming therapeutically engaged. Little
      research, however, has been conducted on therapeutic engagement in corrections
      based substance use treatment. The current study examines the association between
      internal treatment motivation and therapeutic engagement for a sample of 220 male
      substance-using offenders enrolled in a corrections-based treatment program.
      Findings showed that problem recognition and desire for help were associated with
      cognitive indicators of therapeutic engagement, specifically confidence in and
      commitment to treatment. Increased focus on internal motivation for treatment may
      lead to more effective treatment for substance-using offenders. Pretreatment
      motivational interventions therefore are recommended for substance-using
      offenders with low internal motivation for treatment.

PMID- 15559686
TI  - Club drug use among minority substance users in New York City.
AB  - Surveillance data suggests that club drug use (Ecstasy, GHB, ketamine, LSD,
      methamphetamine, PCP and flunitrazepam) has been a predominantly White adolescent
      and young adult phenomenon in the United States. The authors investigated the use
      of club drugs among 323 street-recruited minority substance users in northern New
      York City (66.3% were Hispanic, 23.8% were Black, and 9.9% were White/other race;
      median age = 32 years old). While Whites were more likely than others to have
      used club drugs, club drug use among Hispanics and Blacks was not uncommon; 45.3%
      Hispanics and 56.4% of Blacks reported a lifetime history of club drug use. PCP
      was the most commonly reported club drug used among all racial/ethnic groups.
      Further investigation of club drug use in minority populations is warranted.

PMID- 15559687
TI  - The use of amphetamine in gamma-hydroxybutyrate overdose: a case report.
AB  - A case report of a male presenting with a gamma-hydroxybutyrate (GHB) induced
      coma at a gay-oriented dance event is reported. A friend accompanying the patient
      reported that when the patient started to become stuporous, he attempted to
      revive him with intranasally administered aliquots of crystal methamphetamine.
      Such treatment partially counters the hypotonia of GHB induced coma, resulting in
      "automatic" movements by the patient; however, it does not reverse the cognitive
      effects of the drug. The result increases the difficulty of medical management.
      The authors report the physical findings and implications for increased
      difficulty in managing such patients.

PMID- 15559688
TI  - Changing ethical standards in scientific publication.

PMID- 15559689
TI  - Hip fracture and venous thromboembolism in the elderly.
AB  - Venous thromboembolism (VTE), a highly prevalent vascular disorder, is frequently
      clinically silent, and is often difficult to diagnose. VTE consists of both deep
      vein thrombosis (DVT) and pulmonary embolism (PE), both of which are associated
      with potentially significant morbidity and mortality. With the availability of
      safe and effective antithrombotic therapy, the standard of medical care should be
      the routine use of thromboprophylaxis. The risk of developing VTE increases with
      advancing age, and the performance of surgery to repair a fractured hip increases
      this risk even more. Thus elderly hip fracture patients are always considered to
      be at the highest risk for developing fatal PE. Over the last decade, new
      anticoagulants, such as the factor Xa inhibitor fondaparinux, have been developed
      that specifically target individual components of the coagulation system.
      Fondaparinux is a selective, synthetic factor Xa inhibitor that has been shown to
      significantly reduce the risk of VTE versus enoxaparin in patients undergoing
      surgery for hip fracture. Extended (4-week) prophylaxis with fondaparinux can
      produce a 96% reduction in risk of DVT and an 89% reduction in risk of
      symptomatic VTE events relative to perioperative (1-week) prophylaxis. As the
      only anticoagulant approved in the United States for thromboprophylaxis in hip
      fracture patients, fondaparinux offers more effective prophylaxis against VTE
      without compromising safety.

PMID- 15559690
TI  - Effect of botulinum toxin type A on gait of children who are idiopathic toe
      walkers.
AB  - The purpose of this study was to determine the effects of botulinum toxin type A
      treatment on ankle muscle activity during gait of children who are idiopathic toe
      walkers. Five children who were idiopathic toe-walkers with a mean age was 4.34
      years participated. Gait of the subjects was evaluated prior to, 20 days
      following, and 12 months following bilateral botulinum toxin type A injection of
      the gastrocnemius and soleus muscles. Subjects received physical therapy
      following the 20-day evaluation. Dependent variables were type of foot contact
      pattern and duration of swing-phase tibialis anterior activity and onset of
      stance-phase gastrocnemius relative to ground contact. Prior to treatment 51% of
      foot contacts were with the toe (heel just off the ground) or were digitigrade,
      while the remaining contacts were flat foot or heel strike. At approximately 20
      days following treatment, only 8% of foot contacts were toe contact or
      digitigrade. Prior to treatment, mean gastrocnemius onset was 30 ms prior to foot
      contact and the duration of swing-phase tibialis anterior was only 345 ms.
      Following treatment (and a more normal foot contact pattern), mean gastrocnemius
      onset followed ground contact by 36 ms and tibialis anterior duration increased
      through terminal swing and into the loading response. The posttreatment
      improvement was maintained at 12-month follow-up. It appears that botulinum toxin
      type A treatment normalizes the ankle EMG pattern during gait and a more normal
      foot-strike pattern is obtained. These data are discussed in terms of a
      neuromotor rationale for the rehabilitation of children who are idiopathic toe
      walkers to maintain posttreatment improvements.

PMID- 15559691
TI  - Jones fractures in the elite football player.
AB  - The Jones fracture, defined as a proximal junctional metaphyseal/diaphyseal
      fracture of the fifth metatarsal, presents a challenge to the orthopaedic
      surgeon, especially in the competitive athlete. The purpose of this study is to
      characterize the Jones fracture in the elite athletic community and review the
      variety of treatments for these fractures in the National Football League (NFL).
      Between 1988 and 2002, 4758 elite collegiate football players participated in the
      NFL Combine. All athletes were evaluated clinically and radiographically. There
      were 86 Jones fractures identified in 83 athletes (incidence of 1.8%). Fifty
      three percent (46 of 86) of the fractures were treated surgically. Eighty-nine
      percent (41 of 46) healed without complications and 7% (3 of 46) developed a
      nonunion. Twenty percent (8 of 40) of the fractures treated nonoperatively
      developed a nonunion while 80% (32 of 40) healed. The NFL injury surveillance
      system was also studied and revealed 17 Jones fractures occurred during the
      seasons 1996--2001. All of these fractures were treated with intramedullary screw
      fixation. The union rate was 94% (16 of 17 fractures). A questionnaire was also
      sent to all NFL team physicians regarding their experience with these fractures.
      The concensus was that this is not a common injury, but when it occurs, surgical
      treatment is recommended (77%) over nonsurgical treatment (23%). After reviewing
      the data, it was found that intramedullary screw fixation of Jones fractures is
      the treatment of choice for most physicians who treat elite collegiate and
      professional football athletes.

PMID- 15559692
TI  - Posttraumatic radial club hand.
AB  - Fifteen adult patients with an unstable ununited fracture of the distal third of
      the radius and severe radial deviation deformity resembling a radial club hand
      were retrospectively reviewed at an average of 25 months after operative
      treatment. There were eight women and seven men with an average age of 57 years
      (range, 33-79 years). The average duration of nonunion was 56 months (range, 6
      252 months). Six patients had a concomitant fracture of the ulna and four had
      dislocation of the distal radioulnar joint. Three patients were treated with
      wrist arthrodesis and 12 with plate fixation and autogenous bone grafting. The
      distal ulna was excised and used for bone graft in eight patients. Correction of
      deformity was facilitated by z-lengthening of the brachioradialis and flexor
      carpal radialis in four patients and distraction histogenesis (llizarov) in two
      patients. One patient failed to heal the fracture and was treated with wrist
      arthrodesis. Functional alignment and use of the hand was restored in all
      patients.

PMID- 15559693
TI  - How the pemberton innominate osteotomy really works: an animal study.
AB  - Conventional wisdom holds that the Pemberton innominate osteotomy improves
      acetabular coverage and decreases acetabular volume through hinging of the
      acetabular dome through the triradiate cartilage. The aim of this study was to
      identify the site of hinging through the triradiate cartilage and characterize
      any alteration in acetabular volume produced by this procedure. Pemberton
      innominate osteotomies were performed under fluoroscopic control on six fresh
      immature pig innominate bones. The site of hinging at the triradiate cartilage
      was identified through observation during the procedure. Just prior to and
      immediately after the procedure, the acetabular dimensions were measured and
      recorded. Hinging was observed to occur through the extra-articular portion of
      the ilioischial limb of the triradiate cartilage. No alteration of acetabular
      volume was observed following successful Pemberton innominate osteotomies. The
      Pemberton osteotomy improves femoral head coverage through redirection of the
      acetabulum rather than alteration of acetabular shape.

PMID- 15559694
TI  - Late vascular injury following intertrochanteric fracture reduction with sliding
      hip screw.
AB  - A case involving late injuries to pelvic vessels caused by a sliding hip screw
      penetrating through the acetabulum has not been previously reported. We present
      the case of an 88-year-old man who presented with a retroperitoneal and
      extraperitoneal hematoma 4 months after open reduction and internal fixation of
      an intertrochanteric hip fracture. Surgical exploration showed a laceration of
      the left external iliac artery, which was repaired. However, the sliding hip
      screw was left in place. The patient's condition deteriorated, and he expired 2
      days later. Postmortem examination revealed a laceration of the left internal
      iliac vein. Our calculations show that the compression screw utilized in the
      fixation may not have been properly engaged into the sliding screw.

PMID- 15559695
TI  - Arthroscopic shaver-assisted total hip arthroplasty revision.
AB  - A case report of a 54-year-old man who underwent a revision arthroplasty 13 years
      after his original hip replacement is presented. The patient presented to the
      clinic with a 2-month history of hip pain. Severe pelvic osteolytic lesions were
      seen on radiographs. The revision procedure consisted of debridment of the
      osteolytic lesions and bone grafting. An arthroscopic shaver was used to remove
      the osteolytic lesions proximal to the acetabular cup. Excellent debridment was
      obtained. Cortical bone allograft was the used to fill the void areas behind the
      cup. The patient did well postoperatively with no recurrence of osteolysis as
      seen on radiographs obtained 7 months after surgery. This report presents a
      successful case of pelvic osteolytic debridment with the use of an arthroscopic
      shaver.

PMID- 15559696
TI  - Placement of solid screws with cannulated precision.
AB  - Cannulated screws can be inserted in a precise manner with minimal damage to
      surrounding structures but lack the mechanical strength of solid screws. Our
      method allows the insertion of a solid screw with the precision of the cannulated
      technique. With the use of equipment from a variety of operative sets from one
      manufacturer, a "custom" equipment set can be developed. This "custom" equipment
      set allows the surgeon to benefit from the strength of solid screws while
      preserving the precision of a cannulated system.

PMID- 15559697
TI  - Presidential address: Ramblings of a Redneck Orthopod.

PMID- 15559698
TI  - Ethical pediatrics.

PMID- 15559699
TI  - A 13-year-old girl with neurofibromatosis-1, scoliosis.

PMID- 15559700
TI  - Addressing ethical issues in everyday practice.
AB  - In primary-care practice, just as in critical care, ethical dilemmas challenge
      pediatricians to make choices in the best interests of their patients. Parents
      are important to the growth and development of children and have broad
      responsibility for making virtually all decisions regarding nutrition, clothing,
      housing, education, religion, and medical care. Society's deference to parental
      choice promotes the value of family integrity, ensures the availability of an
      identifiable decision maker, and acknowledges the legitimate role parents play in
      shaping their child's development. However, pediatricians have obligations to
      assess and advocate for the best interests of their patients. This requires that
      physicians reach out to their patients and take the time to listen to children
      and to involve them in their own care. The proper role of a child in planning
      care depends less on chronologic age than on developmental and personal capacity.
      Even young children have a keen awareness of their own clinical situations and
      options and should be involved as best as is possible in decision making. All
      decision making for children should be collaborative among patients, parents, and
      professionals. A situation including an involved child, an informed parent, and a
      caring and compassionate caregiver working collaboratively is most likely to
      result in optimal decisions for pediatric patients. Bartholome concluded in 1995
      that pediatricians should respect children for the persons they are in the
      process of becoming by being willing to assist them to participate to the extent
      of their capacity in making decisions about their health. Combining that view
      with fostering respect for the strongly held beliefs and values of parents is the
      direction pediatricians should travel to make decisions in the best interests of
      children.

PMID- 15559701
TI  - Ethical dilemmas in the treatment of children with disabilities.
AB  - Issues relating to the treatment of children with disabilities, such as
      withholding treatment, organ donation, research, genetic screening, and prenatal
      diagnosis, all present ethical dilemmas. These issues always need to be reviewed
      to determine which ethical considerations apply. Identifying relevant principles,
      one can conclude which take precedence and what is ethically permissible. As with
      so many other medical responsibilities, this can be consulted, learned, practiced
      and improved upon. Pediatricians caring for children with disabilities can study
      and enhance their capacity for ethical reflection, so as to participate fully in
      these important decision-making processes.

PMID- 15559702
TI  - Should children and adolescents undergo genetic testing?
AB  - Genetic testing comes in many shapes and sizes. The decision to undergo genetic
      testing must involve consideration of the medical, psychosocial, and reproductive
      benefits and risks of testing. The evaluation of risks and benefits varies
      significantly both between and within families. Pediatricians should keep up with
      the rapid advances in genetic medicine and the myriad of tests that are being
      developed and marketed. They also need to be familiar with the psychosocial risks
      and benefits that these new tests generate for individuals, families and
      communities. In some situations, genetic testing is merely another diagnostic
      tool; in other situations, genetic testing offers information about the risks for
      future diseases. Pediatricians need to be knowledgeable about tests that are
      indicated clinically and their potential psychosocial implications to best serve
      children, adolescents, and their families.

PMID- 15559703
TI  - Providing palliative care for newborns.
AB  - Palliative care principles may be applied in the NICU, may be necessary, and may
      benefit from the contributions of community pediatricians who have a relationship
      with families undergoing these tragic circumstances. Clinicians across varied
      disciplines can cooperate to provide an environment in the delivery room or NICU
      where palliative care can be integrated into patient and family care plans
      regardless of whether the treatment goal is obtaining a cure, prolonging life, or
      exclusively palliation and comfort until an expected death. Regardless of the
      site of care, the best interests of the patient remain the focus of such care.
      This care should be consistent with the goals and preferences of the family, and
      respectful of their culture and faith traditions. The physical comfort of the
      infant and the emotional, psychosocial, and spiritual well-being of his/her
      family (including siblings and grandparents) all require active management and
      support. Finally, bereavement support should be provided following an infant's
      death to help families integrate their loss into their lives.

PMID- 15559704
TI  - Advising parents about children's participation in clinical research.
AB  - The pediatrician can assist a parent in evaluating the risks and potential
      benefits of clinical research, assessing the qualifications of the research team,
      clarifying a child's understanding of the research, and supporting the parent and
      child throughout the research study. To perform this role, the pediatrician
      should review with the parent and child (if appropriate) the consent document and
      any other available information about the research. If there are unanswered
      questions, the pediatrician should encourage a parent to contact the researcher,
      or offer (with the parent's permission) to contact the researchers on the
      parent's behalf.

PMID- 15559705
TI  - Being the voice for a child.

PMID- 15559706
TI  - Mandatory overtime can hurt a hospital's financial status.

PMID- 15559707
TI  - Brought together by war.

PMID- 15559708
TI  - Goal setting as a strategy for dietary and physical activity behavior change: a
      review of the literature.
AB  - OBJECTIVE: Estimate effectiveness of goal setting for nutrition and physical
      activity behavior change, review the effect of goal-setting characteristics on
      behavior change, and investigate effectiveness of interventions containing goal
      setting. DATA SOURCE: For this review, a literature search was conducted for the
      period January 1977 through December 2003 that included a Current Contents,
      Biosis Previews, Medline, PubMed, PsycINFO, and ERIC search of databases and a
      reference list search. Key words were goal, goal setting, nutrition, diet,
      dietary, physical activity, exercise, behavior change, interventions, and
      fitness. STUDY INCLUSION AND EXCLUSION CRITERIA: The search identified 144
      studies, of which 28 met inclusion criteria for being published in a peer
      reviewed journal and using goal setting in an intervention to modify dietary or
      physical activity behaviors. Excluded from this review were those studies that
      (1) evaluated goal setting cross-sectionally without an intervention; (2) used
      goal setting for behavioral disorders, to improve academic achievement, or in
      sports performance; (3) were reviews. DATA EXTRACTION AND SYNTHESIS: The articles
      were categorized by target audience and secondarily by research focus. Data
      extracted included outcome measure, research rating, purpose, sample, sample
      description, assignment, findings, and goal-setting support. RESULTS: Thirteen of
      the 23 adult studies used a goal-setting effectiveness study design and eight
      produced positive results supporting goal setting. No adolescent or child studies
      used this design. The results were inconclusive for the studies investigating
      goal-setting characteristics (n = 7). Four adult and four child intervention
      evaluation studies showed positive outcomes. No studies reported power
      calculations, and only 32% of the studies were rated as fully supporting goal
      setting. CONCLUSIONS: Goal setting has shown some promise in promoting dietary
      and physical activity behavior change among adults, but methodological issues
      still need to be resolved. The literature with adolescents and children is
      limited, and the authors are not aware of any published studies with this
      audience investigating the independent effect of goal setting on dietary or
      physical activity behavior. Although, goal setting is widely used with children
      and adolescents in nutrition interventions, its effectiveness has yet to be
      reported.

PMID- 15559709
TI  - Stage of change movement across three health behaviors: the role of self
      efficacy.
AB  - PURPOSE: In this study, we examined the influence of self-efficacy in predicting
      stage of change (SOC) movement, without intervention, over a 1-month period for
      smoking cessation, exercise adoption, and dietary fat reduction. DESIGN: The
      design of this study was longitudinal. Patients' stage of change and self
      efficacy were assessed at baseline, and stage of change was reassessed at a 1
      month follow-up. Patients were categorized as (1) Regressors (moved backward at
      least one stage), (2) Stables (no change), or (3) Progressors (moved forward at
      least one stage). Chi-square analyses were used to determine the ability of self
      efficacy to predict stage movement at 1-month follow-up. SETTING: The data were
      collected at a large, inner city, academic hospital in the southeastern United
      States. Patients were attending primary care clinics. SUBJECTS: Five hundred
      fifty-four low income, predominantly African-American, individuals attending
      primary care clinics were participants in the study. MEASURES: Previously
      validated scales of stage of change and self-efficacy from Prochaska's laboratory
      were used in this study. RESULTS: Results showed statistically significant
      differences between predicted and actual SOC movement for smoking cessation,
      exercise adoption, and dietary fat intake reduction. Baseline self-efficacy
      ratings were significantly related to stage progression, regression, and
      stability of stage of change for all three health behaviors. Thirty-seven percent
      of smokers who were predicted to progress on the basis of their self-efficacy
      scores progressed. For exercise adoption and dietary fat reduction, 50% and 44%,
      respectively, of individuals expected to progress at least one stage on the basis
      of self-efficacy scores progressed. CONCLUSION: Self-efficacy influences SOC
      movement for smoking cessation, dietary fat reduction, and exercise adoption.

PMID- 15559710
TI  - Team awareness, problem drinking, and drinking climate: workplace social health
      promotion in a policy context.
AB  - PURPOSE: (1) To determine the effectiveness of classroom health
      promotion/prevention training designed to improve work climate and alcohol
      outcomes; (2) to assess whether such training contributes to improvements in
      problem drinking beyond standard workplace alcohol policies. DESIGN: A cross
      sectional survey assessed employee problem drinking across three time periods.
      This was followed by a prevention intervention study; work groups were randomly
      assigned to an 8-hour training course in workplace social health promotion (Team
      Awareness), a 4-hour informational training course, or a control group. Surveys
      were administered 2 to 4 weeks before and after training and 6 months after
      posttest. SETTING AND SUBJECTS: Employees were surveyed from work departments in
      a large municipality of 3000 workers at three points in time (year, sample, and
      response rates are shown): (1) 1992, n = 1081, 95%; (2) 1995, n = 856, 97%; and
      (3) 1999, n = 587, 73%. Employees in the 1999 survey were recruited from safety
      sensitive departments and were randomly assigned to receive the psychosocial (n =
      201), informational (n = 192), or control (n = 194) condition. INTERVENTION: The
      psychosocial program (Team Awareness) provided skills training in peer referral,
      team building, and stress management. Informational training used a didactic
      review of policy, employee assistance, and drug testing. MEASURES: Self-reports
      measured alcohol use (frequency, drunkenness, hangovers, and problems) and work
      drinking climate (enabling, responsiveness, drinking norms, stigma, and drink
      with co-workers). RESULTS: Employees receiving Team Awareness reduced problem
      drinking from 20% to 11% and working with or missing work because of a hangover
      from 16% to 6%. Information-trained workers also reduced problem drinking from
      18% to 10%. These rates of change contrast with changes in problem drinking seen
      from 1992 (24%) to 1999 (17%). Team Awareness improvements differed significantly
      from control subjects, which showed no change at 13%. Employees receiving Team
      Awareness also showed significant improvements in drinking climate. For example,
      scores on the measure of coworker enabling decreased from pretest (mean = 2.19)
      to posttest (mean = 2.05) and follow up (mean = 1.94). Posttest measures of
      drinking climate also predicted alcohol outcomes at 6 months. CONCLUSION:
      Employers should consider the use of prevention programming as an enhancement to
      standard drug-free workplace efforts. Team Awareness training targets work group
      social health, aligns with employee assistance efforts, and contributes to
      reductions in problem drinking.

PMID- 15559711
TI  - Predictors of physical activity stage of change among adults with physical
      disabilities.
AB  - PURPOSE: To use the Transtheoretical Model (TTM) constructs to examine the most
      important physical activity stage of change predictors for mostly inactive adults
      with physical disabilities. METHODS: A cross-sectional survey completed on the
      Internet. One hundred fifty-one individuals with physical disabilities (50%
      response rate) completed the survey questionnaires. Self-report standardized
      measures were used. RESULTS: A direct discriminant function analysis revealed
      that the most important stage of change predictors were the behavioral (r2 = .88)
      and cognitive (r2 = .50) processes of change, followed by self-efficacy (r2 =
      .33) and decisional balance (r2 = .13). The most accurate stages in prediction
      were the contemplation (76.3%), preparation (58.3%), and precontemplation (40%)
      stages, whereas the least accurate stages were the action (0.0%) and maintenance
      (8.3%) stages. CONCLUSION: Health promoters and educators may use strategies from
      the TTM to develop theory-driven physical activity motivational programs for the
      posited populace. Considering the cross-sectional design, study replication is
      warranted.

PMID- 15559712
TI  - The relationship of stage of change for smoking cessation to stage of change for
      fruit and vegetable consumption and physical activity in a health plan
      population.
AB  - PURPOSE: The purpose of this study was to examine the relationship between stage
      of change for smoking cessation and stage of change for (1) fruit and vegetable
      consumption and (2) physical activity. DESIGN: The data come from a cross
      sectional telephone survey administered to a stratified random sample of health
      plan members (n = 9675). SETTING: This study was conducted at a mixed-model
      health plan with approximately 1 million adult members. SUBJECTS: Respondents
      were adults age 18 and older, who were randomly selected from five health plan
      product groups: commercial fully insured, commercial self-insured, two publicly
      subsidized plans, and Medicare supplemental insurance. Response rates ranged from
      74.7% to 90.1% across these groups. MEASURES: The assessment included
      demographics and stage of change for smoking cessation, physical activity, and
      fruit and vegetable intake. Bivariate relationships among variables were analyzed
      with the use of contingency tables. Ordered logistic regression was used to
      examine the effects of stage of change for fruit and vegetable consumption and
      physical activity on stage of change for smoking while controlling for other
      factors. RESULTS: Stage of change for smoking is more clearly related to stage of
      change for fruit and vegetable consumption (chi2 = 161.3, p < .001; Cramer's V =
      .11, p < .001) than to stage of change for physical activity (chi2 = 89. 7, p <
      .001; Cramer's V = .08, p < .001). However, stage of change for fruit and
      vegetable consumption and physical activity are not strong predictors of stage of
      change for smoking. CONCLUSIONS: This study indicates that stage of change for
      both fruit and vegetable consumption and physical activity are independent
      constructs from stage of change for smoking cessation.

PMID- 15559713
TI  - Neighborhood design and rates of walking and biking to elementary school in 34
      California communities.
AB  - PURPOSE: This study evaluates the relationship between neighborhood design and
      rates of students walking and biking to elementary school. DESIGN: Pairwise
      correlations and multiple regression models were estimated based on a cross
      sectional study of elementary schools and their surrounding neighborhoods.
      Setting and Subjects. Thirty-four (23%) of 150 California public elementary
      schools holding October 1999 Walk to School Day events participated in the study.
      MEASURES: Teachers asked fifth-grade students how they arrived to school 1 week
      before Walk to School Day. 1990 U.S. Census data measured population density and
      number of intersections per street mile, whereas 1998-1999 California Department
      of Education data measured school size, the percentage of students receiving
      public welfare, and the percentage of students of various ethnicities. RESULTS:
      Population density (p = .000) and school size (p = .053) were significantly
      associated with walking and biking rates in regression models controlling for
      number of intersections per street mile, the percentage of students receiving
      public welfare, and the percentage of students of various ethnicities. The number
      of intersections per street mile was associated with walking and biking rates in
      pairwise correlations (p = .003) but not in regression models. CONCLUSIONS: The
      results support the hypothesis that the walking and biking rates are higher in
      denser neighborhoods and to smaller schools but do not support the hypothesis
      that rates are higher in neighborhoods with a high number of intersections per
      street mile. We suggest that detailed data for a larger sample of students would
      allow statistical models to isolate the effect of specific design
      characteristics.

PMID- 15559714
TI  - The relationship between obesity and the prevalence of fast food restaurants:
      state-level analysis.
AB  - PURPOSE: Obesity accounts for approximately 300,000 deaths a year in the United
      States, and prevalence rates have been increasing over the past decade. The
      nutrition environment may be contributing to this epidemic. This study examined
      the relationship between fast food restaurants and obesity on a state-wide basis.
      DESIGN: A one-time cross-sectional analysis of secondary data was used for this
      study. SETTING: The setting for this study was the United States. SUBJECTS: State
      level data were used as the unit of analysis. Alaska was excluded as an outlier,
      and the District of Columbia was added (N = 50). MEASURES: Measures included
      aggregate state-level means for square miles per fast food restaurant, population
      per fast food restaurant, population density, ethnicity, age, gender, physical
      inactivity, fruit and vegetable intake, and obesity rates. Data were obtained
      from the 2002 Behavioral Risk Factor and Surveillance Survey, the 2000 U.S.
      Census, and the 2002 U.S. Yellow Pages. RESULTS: Multiple hierarchal regressions
      revealed that square miles per fast food restaurants and residents per restaurant
      accounted for 6% of the variance in state obesity rates after controlling for
      population density, ethnicity, age, gender, physical inactivity, and fruit and
      vegetable intake. The entire model explained 70% of the total variance in state
      obesity rates. CONCLUSIONS: These results indicate a correlational relationship
      between both the number of residents per fast food restaurant and the square
      miles per fast food restaurants with state-level obesity prevalence. Limitations
      include the use of correlational aggregate data.

PMID- 15559715
TI  - Strategies for health promotion in small businesses.

PMID- 15559716
TI  - Nurse sued when child dies from error in interpreting drug dosage.

PMID- 15559717
TI  - Was there sufficient nurse expert testimony to go to a jury? Case on point:
      Nichols v. Good Samaritan Hospital, 2004 WL 2222384 -CA.

PMID- 15559718
TI  - GA: Nurse on-call 24 hours falls at home: was nurse entitled to workers'
      compensation?

PMID- 15559719
TI  - CA: Nurse errs in giving pitocin to stop labor: father's suit for emotional
      distress fails.

PMID- 15559720
TI  - Ethnic prejudice among nurses has no place in hospital. Case on point: Asileti v.
      California Hospital Medical Center, 2004 WL 2293696 -CA.

PMID- 15559721
TI  - Our future is now!

PMID- 15559722
TI  - Are you ready for some action? Giving voice to the value and vision.

PMID- 15559723
TI  - Monoclonal anti-CD 20 antibody used in non-Hodgkin's lymphoma: a case study.

PMID- 15559724
TI  - Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in
      200 healthy Jordanians.
AB  - Thrombophilia is now considered a multi-causal condition, with interplay of
      acquired genetic risk factors. In order to estimate the frequency of the factor V
      Leiden, prothrombin G20210A, and MTHFR C677T mutations in the Jordanian
      population, we screened 200 healthy Jordanian individuals. 40% were females. Mean
      age was 32.1 years for males and 30.0 years for female participants. A PCR method
      detected 15.0% factor V Leiden (87% heterozygous, 13% homozygous), 2% prothrombin
      G20210A (100% heterozygous), and 24% MTHFR C677T (67% heterozygous, 33%
      homozygous). We conclude that the prevalence of factor V Leiden and MTHFR C677T
      is elevated in this population of Jordanians. However the incidence of G20210A is
      relatively low. Quantification of these genetic thrombosis risk factors in
      various populations will contribute to a better understanding of the interaction
      of genetic and environmental risk factors.

PMID- 15559725
TI  - The clinical consequences and diagnosis of hypothyroidism.
AB  - Hypothyroidism represents a common disorder especially in older women. Left
      untreated, it can lead to abnormalities in lipid metabolism and subsequent
      progression to overt hypothyroidism, with significant clinical consequences of
      myocardial infarction and stroke. More research needs to be performed to
      investigate the link between subclinical hypothyroidism and cardiovascular
      disease risk and to evaluate the health and economic outcomes of randomized
      trials of TSH screening.

PMID- 15559726
TI  - Assessment of the graduate studies background of CLS faculty in university-based
      programs.
AB  - OBJECTIVE: To identify the degrees held and the graduate majors or fields of
      study for faculty teaching full-time and part-time in university-based,
      baccalaureate-degree clinical laboratory science/medical technology (CLS/MT)
      programs. DESIGN AND PARTICIPANTS: A survey and letter of project explanation was
      sent electronically to the 110 program directors of NAACLS-accredited university
      based CLS/MT programs in the United States in May, 2003. Program directors were
      requested to provide for each full-time and part-time faculty member the
      following information: titles for all degrees held, major/field of study for each
      degree held, all specialist certifications held, all other formal degrees or
      certificates held, and all courses/areas taught in the CLS curriculum. RESULTS:
      Information was provided on 288 faculty in 52 CLS/MT programs, for a response
      rate of 47%. The majority of faculty (75%) described were full-time. A doctorate
      was held by 43% of the reported faculty, while 46% held a master's degree as
      their highest degree, and 11 % only a BS in CLS or in biology plus a certificate
      from a hospital-based CLS/MT program. Graduate degrees in a science major or
      field represented 52% of the degrees held by the reported faculty, while 48% of
      the graduate degrees were in education, public health, or administration. Only
      13% of the reported faculty held master's degrees specifically in CLS. Detailed
      results are provided for degrees held, majors/fields of study, and specialist
      certifications by specific courses/areas of the curriculum taught. CONCLUSIONS:
      The results of this survey indicate that many faculty teaching in university
      based CLS/MT programs are extending their preparation as scientists to the
      graduate level. This should prepare these faculty for their responsibilities in
      not only teaching but also research. A case cannot be made that a doctorate, as
      opposed to a master's degree, is viewed as the 'terminal degree' as less than
      half of the reported faculty in this study as well as others, held a doctorate.
      The results reported provide a national perspective on the graduate backgrounds
      of CLS faculty for comparison to an individual program's faculty during
      programmatic or institutional accreditation reviews.

PMID- 15559727
TI  - Rapid detection of West Nile Virus in birds using the VecTest WNV Antigen Assay.
AB  - OBJECTIVE: To determine if the VecTest West Nile Virus Antigen Assay (for testing
      mosquitoes) could be adapted to detect West Nile virus (WNV) rapidly and
      accurately in birds for screening purposes. DESIGN: Cloacal swabs and tissue
      (kidney and spleen) were harvested from 40 fresh dead birds. The VecTest was used
      for each swab specimen for detection of WNV; PCR was used for each tissue
      specimen for confirmation of WNV. SETTING: Mississippi Veterinary Diagnostic
      Laboratory (MVDL) in Jackson Mississippi and College of Veterinary Medicine
      Mississippi State University (CVM-MSU) in Starkville Mississippi.
      SPECIMENS/SUBJECTS: Forty birds of the Corvid family (31 blue jays and 9 American
      crows) were included in the study. Fresh dead birds that died from no obvious
      cause were submitted for testing. RESULTS: VecTest results were 35 positives and
      5 negatives. PCR results were 35 positives and 5 negatives. CONCLUSION: The
      VecTest showed 100% accuracy.

PMID- 15559728
TI  - Advances in understanding the molecular pathogenesis of neoplastic hematologic
      disorders.
AB  - The 45th Annual Meeting of the American Society of Hematology was held December 6
      9, 2003, at the San Diego Convention Center in California. As with past meetings,
      there were exciting new developments, comprehensive educational programs, and
      phenomenal exhibits. There was also an ever increasing ASCLS presence at the
      meeting, as more hematology/hemostasis educators and researchers are finding
      their way to this very excellent scientific meeting. A group of us who attended
      the meeting would like to share with our colleagues who were unable to attend
      some of the new information in select areas, covered in the following two
      articles with a third to follow in the next issue of CLS. While a comprehensive
      summary of the entire meeting would be desirable, the scope of the meeting makes
      such an endeavor unfeasible. Consequently, we have chosen the areas of
      myeloproliferative disorders and myelodysplastic syndromes, acute lymphocytic
      leukemias, and acute myelocytic leukemias.

PMID- 15559729
TI  - The myelodysplastic syndromes and myeloproliferative disorders.
AB  - Our understanding of the exact molecular and genetic alterations responsible for
      the evolution of the diverse diseases included under the myelodysplastic and
      myeloproliferative disorders lags behind that of the acute leukemias and CML.
      However, progress is being made, and new tests for molecular markers (increased
      PRV-1/CD177, decreased Mpl expression) are being developed. While in the past,
      treatment for both groups of diseases was primarily supportive, an improved
      understanding of the underlying pathobiology has led to new treatments with
      promising preliminary results. The laboratory's role in the diagnosis, prognosis,
      and determination of efficacy of treatment will continue to expand as new tests
      become available.

PMID- 15559730
TI  - Advances in acute lymphoblastic leukemia.
AB  - DATA SOURCES: Current literature. DATA SYNTHESIS: Acute lymphoblastic leukemia
      (ALL) is a stem cell disorder characterized by an overproduction of lymphoblasts
      in the bone marrow that eventually spill into circulation, producing
      lymphocytosis. As with the other acute leukemias, the most common symptoms
      experienced by patients include fatigue, bleeding, and recurrent infections
      resulting from the suppression of normal hematopoiesis in the bone marrow by the
      accumulating blasts. ALL primarily affects children and exhibits the best
      response to standard chemotherapy as compared to acute myeloblastic leukemias
      (AML). Further, remission rates are highest among ALL patients, many of whom are
      experiencing sustained remissions suggesting cure. In light of early treatment
      successes, researchers began to investigate modifications of standard treatment
      regimens to accommodate variability in weight, age, and response to therapy among
      children with ALL. Individualized treatment plans were implemented where some
      patients received a reduced intensity course of therapy to minimize drug toxicity
      while others received drug intensification to maximize response. More recently,
      research efforts have been directed at the elucidation of leukemogenic mechanisms
      implicated in ALL to identify specific protein mutants that can be used to design
      drugs tailored to interfere with the activity of these mutant protein targets.
      Identification of chimeric proteins produced from chromosomal translocations and
      gene expression profiles from microarray analyses are the primary techniques used
      to identify the potential therapeutic targets. CONCLUSION: Several reliable
      prognostic indicators have been identified and are being used to improve
      therapeutic planning and outcome prediction in ALL patients. Individualized
      treatment regimens have been developed based on the specific characteristics of
      each patient to minimize treatment related adverse events and maximize response.
      Through the use of cytogenetic, molecular, and microarray testing, ALL
      classification schemes have improved and potential therapeutic targets have been
      identified. It is anticipated that the next major advance in the treatment of ALL
      will involve the use of designer therapies developed to specifically interfere
      with particular molecular abnormalities producing the leukemogenic aberration to
      the normal signal transduction pathways.

PMID- 15559731
TI  - Anger cognitions and cardiovascular recovery following provocation.
AB  - The current study describes the creation and validation of the Anger Cognitions
      Inventory (ACI) to assess the cognitive appraisals associated with resentful and
      reflective anger. The ACI was created based on a content analysis of self-reports
      of participants' thoughts and feelings following anger provocation in the
      laboratory. Exploratory and confirmatory factor analyses on two separate college
      student samples (N = 267 and N = 276, respectively) revealed five subscales which
      could validly be grouped into resentful and reflective anger. Convergent and
      divergent validity data showed that resentful anger correlated positively with
      anger-out/trait anger and reflective anger correlated positively with anger
      in/brooding. A second study showed positive correlations between rumination and
      delayed cardiovascular recovery following anger provocation. Limitations of both
      studies include restricted samples which limit generalizability of results and
      cardiovascular recovery data collected in Study II which does not include
      assessment of autonomic balance between vagal and sympathetic responsivity.

PMID- 15559732
TI  - Self-efficacy and choice of coping strategies for tolerating acute pain.
AB  - Participants who reported either low or high self-efficacy for tolerating painful
      stimuli were randomly assigned to conditions, in which they either did or did not
      have a choice of strategies for coping with arm shock. Choice and self-efficacy
      were positively associated with increases in perceived control. Being given a
      choice, in comparison to having no choice, led to increased tolerance of arm
      shock and lower pain reports for those with high self-efficacy. Providing a
      choice of strategies did not benefit those with low self-efficacy. This study
      demonstrates that the benefits of allowing individuals the opportunity of
      choosing among an array of coping options depend on a prior conviction that one
      is able to cope.

PMID- 15559733
TI  - Testing factorial validity and gender invariance of the pain catastrophizing
      scale.
AB  - Recent research has indicated that the Pain Catastrophizing Scale (PCS) is a
      reliable measure that taps three dimensions of a singular construct. Gender
      differences have been found consistently in catastrophizing, with women reporting
      significantly higher scores than men on the PCS. This study was designed to cross
      validate the factor structure of the PCS, independently for men and women,
      through second-order confirmatory factor analysis. Results indicate that the
      second-order models provide a good fit to the data. The conceptualization of
      catastrophizing as a singular latent construct, within a hierarchical factorial
      structure that consists of three first-order factors--rumination, magnification,
      and helplessness, was supported for both men and women. The second research
      objective was to test the two models for gender equivalence. Results indicate
      that all constraints held across gender. Together, these findings support the
      psychometric soundness of the PCS and indicate that the gender differences found
      are not due to an inadequate fit of the measurement or structural model.

PMID- 15559734
TI  - Predictors of cognitive appraisals following genetic testing for BRCA1 and BRCA2
      mutations.
AB  - The objectives of this study were (1) to describe perceptions of stress and
      confidence following genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations and
      (2) to identify predictors of these processes. Participants were 130 high-risk
      women affected with cancer who received BRCA1/2 test results. Individual
      difference characteristics and interpersonal factors were measured by self-report
      before genetic counseling and perceptions of stress and confidence were evaluated
      by self-report 1 month following disclosure of test results. BRCA1/2 test results
      had a significant effect only on perceptions of stress (beta = 0.38, p = 0.0001),
      while trait anxiety had a significant effect on both perceptions of stress (beta
      = 0.44, p = 0.0001) and confidence (beta = -0.41, p = 0.001). These results
      suggest that interventions designed to address perceptions of stress related to
      medical decision-making and familial concerns may need to be targeted to BRCA1/2
      mutation carriers and individuals who are highly anxious.

PMID- 15559735
TI  - Examination of the short-term efficacy of a parent-based intervention to prevent
      skin cancer.
AB  - The research evaluated an intervention strategy designed to prevent skin cancer
      in young adolescents. The intervention used parents as change agents to
      effectively communicate the risks of skin cancer and encourage their children to
      avoid high-risk sun-related behaviors while increasing positive sun-safe
      behaviors. Three hundred and forty parents in two regions of the United States
      were educated about the dangers of risky sun behaviors and how to convey
      information about skin cancer prevention to their children. Parents were then
      encouraged to talk with their children about these issues over a 1-month period
      prior to the onset of summer. Following this time period, children whose parents
      received and implemented the intervention materials were compared with a control
      sample of 129 children. These two groups were matched on age, gender, and school
      on number of sunburns and sunburn severity, attitudes and beliefs, and sunbathing
      behavior. Children in the treatment condition differed significantly from
      controls in the predicted directions on all outcome variables. The findings are
      discussed in terms of reducing skin cancer risk behaviors of children via parent
      based intervention approaches.

PMID- 15559736
TI  - Preliminary investigation of the advertising and availability of PREPs, the new
      "safe" tobacco products.
AB  - The tobacco industry recently introduced a new set of "safe" cigarettes and
      nicotine delivery devices that purportedly entail reduced tobacco-related disease
      risk due to their lower level of some carcinogens and toxins. Little is know
      about the biological impact of these potential reduced exposure products (PREPs)
      and nothing is known about their advertising and availability. Hence, two pilot
      studies were conducted to examine the latter issues for the first time. In Study
      1, we examined tobacco ads in 10 popular magazines 1998--2002 and found that only
      1% of ads were for PREPs. In Study 2, we attempted to purchase PREPs in a random
      sample of 113 small stores and found that only 4.4% sold any PREP. These
      preliminary findings tentatively suggest that the industry might not yet be
      heavily invested in products that have the potential to increase tobacco use by
      decreasing its perceived harm. Studies with larger samples are recommended.

PMID- 15559737
TI  - The will to 'will' and the mind to 'mind'.

PMID- 15559738
TI  - Understanding variation in cardiopulmonary bypass: Statistical Process Control
      Theory.

PMID- 15559739
TI  - An ultrafiltration technique for directly reinfusing residual cardiopulmonary
      bypass blood.
AB  - Given the shortages of banked blood, the risks of transfusion reactions, disease
      transmissions, and transfusion errors, we perfusionists must find ways to avoid
      blood transfusions. At the end of any given bypass run, there is residual blood
      left in the bypass circuit, the perfusionist must get this blood back to the
      patient. Most commonly either a cell saver or a hemoconcentrator (HC) has been
      used, in some fashion, to reinfuse residual circuit blood. The ideal method
      should: 1) be simple; 2) raise the hematocrit (HCT); 3) allow for changes in the
      patient's volume status; and 4) not compromise the integrity of the
      cardiopulmonary bypass (CPB) circuit allowing for rapid re-institution of CPB. We
      describe a technique in which residual CPB circuit blood is pumped through an HC
      directly to the patient via a 3/16-inch diameter line into a 16-gauge intravenous
      needle positioned in a peripheral or central vein. This allows the perfusionist
      to give back concentrated blood that is protein-rich while maintaining the above
      criteria.

PMID- 15559740
TI  - Internet-based virtual classroom and educational management software enhance
      students' didactic and clinical experiences in perfusion education programs.
AB  - A challenge faced by many university-based perfusion education (PE) programs is
      the need for student clinical rotations at hospital locations that are
      geographically disparate from the main educational campus. The problem has been
      addressed through the employment of distance-learning environments. The purpose
      of this educational study is to evaluate the effectiveness of this teaching model
      as it is applied to PE. Web-based virtual classroom (VC) environments and
      educational management system (EMS) software were implemented independently and
      as adjuncts to live, interactive Internet-based audio/video transmission from
      classroom to classroom in multiple university-based PE programs. These Internet
      environments have been used in a variety of ways including: 1) forum for
      communication between the university faculty, students, and preceptors at
      clinical sites, 2) didactic lectures from expert clinicians to students assigned
      to distant clinical sites, 3) small group problem-based-learning modules designed
      to enhance students analytical skills, and 4) conversion of traditional face-to
      face lectures to asynchronous learning modules. Hypotheses and measures of
      student and faculty satisfaction, clinical experience, and learning outcomes are
      proposed, and some early student feedback was collected. For curricula that
      emphasize both didactic and clinical education, the use of Internet-based VC and
      EMS software provides significant advancements over traditional models.
      Recognized advantages include: 1) improved communications between the college
      faculty and the students and clinical preceptors, 2) enhanced access to a
      national network of clinical experts in specialized techniques, 3) expanded
      opportunity for student distant clinical rotations with continued didactic course
      work, and 4) improved continuity and consistency of clinical experiences between
      students through implementation of asynchronous learning modules. Students
      recognize the learning efficiency of on-line information presentation but still
      prefer the traditional face-to-face classroom environment. Traditional paradigms
      impose limitations that are rooted in dependence upon the students and
      instructors being physically located in the same place at the same time. These
      represents significant impediments for PE programs that use geographically
      separate clinical sites to provide clinical experience. Historically this has led
      to a disintegration of the presentation of theory, and a reduction in the
      quantity or quality of clinical experience opportunities. New PE models help to
      eliminate limitations and improve the quality of education especially in the face
      of economic challenges. Perfusion education students and faculty will have to
      work together to find computer-based offerings that are equivalent to traditional
      classroom methods.

PMID- 15559741
TI  - Removal of glucose from the cardiopulmonary bypass prime: a prospective clinical
      audit.
AB  - To quantify our decision for the removal of glucose and the use of mannitol as a
      substitute osmotic agent in the cardiopulmonary bypass prime, we conducted a
      prospective clinical audit to evaluate the effects of this change on patient
      outcomes. Data were prospectively collected for 172 consecutive routine cardiac
      surgery patients. The first 85 patients (Surgeon A, 42 patients [Group 1],
      Surgeon B, 43 patients [Group 2]) received 1000 mL Plasmalyte 148 + 5% glucose as
      per institutional protocol. The remaining priming volume for each group consisted
      of 500 mL hemaccel or 4% albumin, 50 mL 8.4% sodium bicarbonate, 100 mL
      Hartmann's solution. The change to a glucose-free prime was then initiated,
      substituting Plasmalyte 148 (without 5% glucose) for the Plasmalyte 148 + 5%
      glucose, in addition 12.5 g mannitol was administered following delivery of
      cardioplegia to the patients operated on by Surgeon B. Surgeon A would not
      include mannitol at this time. Forty-one patients operated by Surgeon A (Group 3)
      subsequently received Plasmalyte 148, and 46 patients operated on by Surgeon B
      (Group 4) received Plasmalyte 148 plus mannitol. Analysis was performed
      stratified by surgeon to quantify the effects of removing glucose from the prime.
      Comparisons were made between groups 1 and 3, and 2 and 4. Net fluid changes were
      recorded from pre-CPB, up to 24-h postoperatively. Intraoperative data collection
      included serum glucose, hematocrit, osmolality, return to rhythm, arrhythmias,
      and blood transfusions. Post-operative variables, including cardiac enzymes,
      arrhythmias, intubation time, length of stay, and mortality were also collected.
      Removal of glucose from the CPB prime resulted in a lower serum glucose
      concentration (mmol/L) during CPB (Gp 1 [13.6] vs. Gp 3 [5.4]; Gp 2 [14.7] vs. Gp
      4 [5.4], p < .05). The addition of 12.5 g of mannitol to the CPB prime resulted
      in a significantly lower net fluid gain (mL) 24 h postoperatively (Gp 2[2792] vs.
      Gp 4 [1970], p < .05) and greater CPB hematocrit (%) (Gp 2 [24.3] vs. Gp 4 [26],
      p < .05). No other results were found to be significant (except CPB plasma
      osmolality (Groups 2 and 4) and sodium concentration [Groups 1 and 3]). The
      results of our audit provide an evidence base to support our change in practice
      to utilize nonglucose primes.

PMID- 15559742
TI  - A versatile extracorporeal circuit for use during repair of descending and
      thoracoabdominal aortic aneurysms in high-risk patients with cardiac and/or
      pulmonary dysfunction: a novel approach to a significant perfusion management
      dilemma.
AB  - The incidence of ischemic complications associated with repair of descending and
      thoracoabdominal aortic aneurysms has been significantly reduced by the use of
      distal aortic perfusion with moderate hypothermia, cerebral spinal fluid
      drainage, and segmental sequential clamping techniques. However, because the
      maintenance of proximal perfusion, the adequacy of left heart bypass (LHB), and
      the ability to ventilate patients on only one lung are all dependent on
      ventricular and pulmonary function, high-risk patients with descending and/or
      thoracoabdominal aortic aneurysms in the presence of cardiopulmonary
      insufficiency or instability present a difficult challenge for the surgical team.
      Traditional closed LHB circuits become nonfunctional in the event of cardiac
      arrest or refractory arrhythmias that create hemodynamic instability and are
      unable to provide necessary pulmonary support if the patient fails to ventilate
      adequately on one lung during thoracotomy. Furthermore, converting a patient from
      closed LHB to traditional venoarterial cardiopulmonary bypass (CPB) is frequently
      difficult, especially when the perfusionist works without the benefit of extra
      personnel to assist during such crises. Consequently, a modified extracorporeal
      circuit was designed to provide closed LHB with desired therapeutic adjuncts
      while also satisfying the additional need for a rapid infusion device, a source
      of supplemental ventilation/oxygenation, and, if necessary, the ability to
      convert the patient to venoarterial CPB conveniently in the event of cardiac
      and/or pulmonary failure during surgery to repair descending and/or
      thoracoabdominal aortic aneurysms.

PMID- 15559743
TI  - Database review of possible factors influencing point-of-care platelet gel
      manufacture.
AB  - The application of autologous platelet gel (APG) to surgical wounds has been
      advocated during the last 10 years to speed bone and wound healing, minimize
      infection, and modify postoperative pain. There are few data available to confirm
      these claims. Prior to organized study, consistency and agreement in manufacture
      of the APG is needed. In this study, an attempt is made to isolate factors that
      are important in developing a consistent gel. A database review was performed to
      determine factors that affect PG quality and function. Quality was assessed by
      platelet count and fibrinogen concentration, whereas function was assessed by an
      arbitrary scale of gelling, in which a "1" was equal to a soup texture, "3" equal
      to a "Jell-O" consistency, whereas a grade of "2" was somewhere in between. Data
      specific to the blood draw and platelet-rich plasma sequestration were collected.
      Two hundred and sixty cases of APG production were reviewed. The volume of blood
      drawn was dependent on the machine used. Gelling of the APG was independent of
      platelet count and fibrinogen concentration. Gels that were rated soupy had an
      average platelet count of 540 K/microL+/-327 K/microL and a fibrinogen
      concentration of 225 mg/dL+/-76 mg/dL whereas a firm gel had an average platelet
      count of 486 K/microL+/-264 K/microL and a fibrinogen concentration of 229
      mg/dL+/-78 mg/dL. The manner in which the blood was drawn along with the site
      from which the blood was drawn influenced the platelet concentration of the
      platelet-rich plasma. Optimal platelet counts were obtained when blood was drawn
      from a peripheral vein and sequestration was performed with the Medtronic
      Sequestra or the Medtronic Magellan. Ultimate gelling of PG is independent of
      fibrinogen and platelet concentrations. This work suggests a need for further
      research into the manufacture of APG.

PMID- 15559744
TI  - End-tidal CO2 for prediction of cardiac output following weaning from
      cardiopulmonary bypass.
AB  - This prospective study included 32 patients undergoing cardiopulmonary bypass
      (CPB) for elective coronary artery bypass grafting correlates the respiratory end
      tidal CO2 (ETCO2) during partial separation from CPB with cardiac output (CO)
      following weaning from CPB. After induction of general anesthesia, a pulmonary
      artery catheter was inserted for measurement of cardiac output by thermodilution.
      Patients were monitored using a 5-lead ECG, pulse oximeter, invasive blood
      pressure monitoring, rectal temperature probe, and end-tidal capnography. At the
      end of surgery, patients were weaned from CPB in a stepwise fashion. Respiratory
      ETCO2 and in-line venous oximetry were continuously monitored during weaning. The
      ETCO2 was recorded at quarter pump flow and after complete weaning from CPB.
      Following weaning from CPB, CO was measured by thermodilution. The CO values were
      correlated with the ETCO2 during partial bypass and following weaning from
      bypass. Regression analysis of ETCO2 at quarter-flow and post-bypass CO showed
      significant correlation (r = 0.57, p < .001). Also, regression analysis of ETCO2
      after complete weaning from bypass and post-bypass CO showed significant
      correlation (r = 0.6, p = .002). The correlation between ETCO2 and CO showed that
      an ETCO2 >30 mm Hg during partial CPB will always predict an adequate CO
      following weaning from CPB. An ETCO2 <30 mm Hg may denote either a low or a
      normal cardiac output and hence other predictive parameters such as SvO2 must be
      added.

PMID- 15559745
TI  - The Hemochron Response RxDx heparin and protamine dosing system.
AB  - The use of dosing assays to calculate heparin and protamine dose requirements
      during cardiac surgery has been shown to significantly improve overall
      postoperative patient outcome. When patients are managed with an individualized
      dosing system, intraoperative and postoperative transfusion requirements and
      bleeding are reduced. The Hemochron RxDx system is widely used as a complement to
      traditional activated clotting time testing to optimize anticoagulation
      management. The system consists of the heparin response test, the protamine
      response test, and the protamine dose assay. All are modifications of the
      activated clotting time using either Celite (Celite Corporation, Santa Barbara,
      CA) or kaolin as the activator. Dosing is calculated manually using earlier
      version Hemochron instruments (model 801) or automatically with the Hemochron
      8000 or with the early versions of the Hemochron Response and the personal
      digital assistant (PDA) RxDx calculator. Missing from available user options is
      an automated RxDx system for the Response. A study was conducted at four clinical
      sites to compare recently developed Response RxDx software, which eliminates the
      need for the PDA RxDx calculator, to the existing Hemochron 8000 RxDx and to the
      Response-PDA RxDx systems. Similar to the current system, the operator inputs the
      patient's height, weight, and gender, and the software automatically calculates
      the blood volume. Using the clotting times determined on the Response, bolus
      heparin and protamine doses and any additional heparin and protamine requirements
      are calculated automatically. Data were collected from 76 patients, of which, 64
      patients were on pump, 11 patients were off pump, and 1 patient was converted
      from off to on pump. The Response estimated blood volume calculations showed a
      correlation coefficient of 0.989 when compared with available systems. A good
      correlation was also observed for the bolus heparin (r = 0.925) and protamine
      doses (r = 0.900) with equivalence confirmed by a paired student's t test. These
      data confirm that the Response RxDx system yields results that are identical (P >
      0.05) to those obtained using the Hemochron 8000 RxDx or Response-PDA RxDx
      calculator. The Response RxDx also offers expanded user options related to blood
      volume limits, expanded clotting time ranges for presetting default values, and
      flexibility in test sequence. Case records can be printed or downloaded to a PC
      via the HRDM data management program. The Hemochron Response RxDx represents a
      complete anticoagulation management system for the cardiac surgical patient.

PMID- 15559746
TI  - Cardiopulmonary bypass: it's not the size, it's how you use it! Review of a
      comprehensive blood-conservation strategy.
AB  - Several of the manufacturers of cardiopulmonary bypass equipment have recently
      introduced new miniature cardiopulmonary bypass systems. New advancements in
      cardiopulmonary bypass technology are almost always of interest to the perfusion
      community. However, the question arises, what advantages do these systems offer
      over our present technology? The manufacturers claim that these new systems will
      add to our perfusion armamentarium by offering us an opportunity to further
      reduce priming volume and the surface area to which the blood is exposed. Our
      group, in the Department of Cardiac Surgery at Boston Medical Center has been
      involved in the development of a comprehensive blood conservation strategy since
      1994. Our published data clearly demonstrates improved clinical outcomes using
      coated circuit technology as part of a comprehensive blood conservation strategy.
      In an effort to clearly evaluate this new technology, in this article we review
      our current technique at Boston Medical Center.

PMID- 15559747
TI  - The basic science aspect of donor heart preservation: a review.
AB  - In cardiac transplantation, the transport time between harvest and recipient is
      limited by the viability of the donor heart. The problem of viability is a
      consistent limitation in cardiac transplantation. Since the 1960s, techniques,
      including hypothermia, perfusion, oxygenation, and hyperbaria, have been used to
      prolong the preservation of the transplantable heart. Continuing development of
      cardioplegic solutions has minimized edema and oxygen radical formation, which
      have resulted in extension of the donor heart viability. New research into the
      events leading to necrosis, oncosis, and apoptosis may allow further advancement
      of protective cardioplegic solutions in combination with technology of
      transporting the heart. With a prolonged preservation time there is potential to
      increase the donor pool and ultimately improve post-operative outcomes.

PMID- 15559748
TI  - Stem cells for regeneration of cardiac tissues: current findings and future
      applications.

PMID- 15559749
TI  - Precise control of PCO2 during cardiopulmonary bypass. 1980.

PMID- 15559750
TI  - The clock-drawing test: a critique.

PMID- 15559752
TI  - Luigi Amaducci memorial award winner's paper 2003. A neurologist's view of
      Alzheimer's disease and dementia.
AB  - Senile dementia was the third most common admission diagnosis for New York
      psychiatric hospitals at the start of the twentieth century and the distinction
      between vascular and senile dementia was understood by psychiatrists even then.
      The term Alzheimer's disease (AD) was originally introduced to distinguish a pre
      senile dementia from the common general paresis, but Alzheimer raised the
      possibility that pre-senile AD might not be distinguishable in clinical or
      histological terms from senile dementia. By the late 1970s it had become clear
      that the most common disorder producing dementia in elderly people was clinically
      and pathologically identical to pre-senile AD. AD is malignant, reducing
      remaining life expectancy by almost half and raising the risk of death over five
      years threefold (cancer raises it fourfold). Synapse loss associated with beta
      amyloid oligomers is a strong determinant of cognitive decline in patients with
      AD. Tau-containing neurofibrillary tangles usefully track disease severity.
      Unmodifiable risk factors include mutations in three genes which affect the
      production or metabolism of beta amyloid, the risk factor gene for Apolipoprotein
      [see symol in text]4 and female gender. The overriding risk factor is age, the
      prevalence of AD doubling with every five years of age until 90. Low education,
      head injury and low folate levels are examples of potentially modifiable risk
      factors. Since a delay of onset of five years would halve the number of patients
      with the disease, clinical trials for such putative protective factors as
      estrogens, folic acid, vitamin E, statins, and NSAIDs have begun. Cognitive and
      leisure activity may be protective against the development of AD but any
      protective function can only be confirmed by clinical trials.

PMID- 15559753
TI  - The Informant Questionnaire on cognitive decline in the elderly (IQCODE): a
      review.
AB  - BACKGROUND AND AIMS: The IQCODE is widely used as a screening test for dementia,
      particularly where the subject is unable to undergo direct cognitive testing or
      for screening in populations with low levels of education and literacy. This
      review draws together research on the psychometric properties and validity of the
      IQCODE. METHOD: A systematic search of the literature was carried out using three
      databases. RESULTS: The review shows that the questionnaire has high reliability
      and measures a single general factor of cognitive decline. It validly reflects
      past cognitive decline, performs at least as well at screening as conventional
      cognitive screening tests, predicts incident dementia, and correlates with a wide
      range of cognitive tests. A particular strength is that the IQCODE is relatively
      unaffected by education and pre-morbid ability or by proficiency in the culture's
      dominant language. The disadvantage of the IQCODE is that it is affected by
      informant characteristics such as depression and anxiety in the informant and the
      quality of the relationship between the informant and the subject. CONCLUSIONS:
      Because the IQCODE provides information complementary to brief cognitive tests,
      harnessing them together can improve screening accuracy.

PMID- 15559754
TI  - A systematic review of the association between the Behavioral and Psychological
      Symptoms of Dementia and burden of care.
AB  - BACKGROUND: Several reports have indicated that the Behavioral and Psychological
      Symptoms of Dementia (BPSD) are associated with increased burden of care, carer
      depression and increased rates of institutionalization of patients. The present
      study aims to review the association between these variables in cross-sectional
      as well as longitudinal studies. METHODS: Systematic review and meta-analysis of
      all available information published in English between January 1990 and December
      2001 was made. Case-reports, case-series and studies with 20 or fewer subjects
      were excluded from the analyses. RESULTS: Thirty articles are included in the
      review of cross-sectional data and 12 in the systematic review of longitudinal
      data. Pooled correlation coefficients were generated for the relationship between
      BPSD and caregiver burden (r(pooled) = 0.57; 95% CI = 0.52 to 0.62), caregiver
      psychological distress (r(pooled) = 0.41; 95% CI = 0.32 to 0.49) and caregiver
      depression (r(pooled) = 0.30; 95% CI= 0.21 to 0.39), suggesting that these
      concepts have a moderately strong association. Multivariate data, on the whole,
      further supported the notion that BPSD are a predictor of burden of care and of
      psychological distress and depression. Limited longitudinal data made clarifying
      the temporal relationahip between BPSD and the psychological sequelae of care
      (PSC) difficult. The limited data pertaining to the relationship between BPSD and
      institutionalization suggest that caregiver variables may be more important in
      predicting institutionalization than BPSD. Methodological issues and limitations
      associated with this type of investigation were also considered. CONCLUSION: The
      results of this review support, but do not conclusively establish, the
      association between BPSD and PSC. We propose that the concept of burden of care
      be abandoned in favor of more clinically relevant outcomes such as caregiver
      depression.

PMID- 15559755
TI  - Apolipoprotein E polymorphism and age of onset for Alzheimer's disease in a bi
      ethnic sample.
AB  - OBJECTIVE: This study examined the association between the Apolipoprotein-E
      epsilon4 allele (APOE epsilon4) and age of disease onset in a bi-ethnic sample of
      community dwelling Alzheimer's disease (AD) patients. DESIGN: Cross-sectional
      study of AD patients evaluated at a University-affiliated outpatient memory
      disorders clinic. SUBJECTS: A clinic-based cohort of white non-Hispanic (WNH;
      n=601) and white Hispanic (WH; n = 359) patients diagnosed with possible or
      probable AD according to NINCDS-ADRDA diagnostic criteria. MEASURES: Global
      cognitive functioning of the subjects was evaluated using the Mini-mental State
      Exam. The age of onset of AD was calculated from the patient's current age minus
      the reported duration of disease obtained from a knowledgeable family member.
      RESULTS: A significant relationship was discovered between APOE epsilon4 and age
      of onset for WNH, with lower ages of onset among patients carrying the
      epsilon4/epsilon4 and epsilon3/epsilon4 genotypes in relation to patients with
      the epsilon3/epsilon3 genotype. The results revealed a more modest effect for
      APOE genotype in the WH cohort, with a lower age of onset witnessed among
      epsilon4 positive patients (epsilon2/epsilon4, epsilon3/epsilon4 and
      epsilon4/epsilon4 genotypes) in comparison to epsilon4 negative patients
      (epsilon2/epsilon2, epsilon2/epsilon3 and epsilon3/epsilon3 genotypes).
      CONCLUSION: The association between the epsilon4 allele and earlier age of onset
      was more pronounced in WNH compared to WH patients, suggesting the impact of APOE
      polymorphism on clinical phenotype may be different for distinct ethnic groups in
      the U.S.

PMID- 15559756
TI  - Body mass index and white matter lesions in elderly women. An 18-year
      longitudinal study.
AB  - BACKGROUND: We investigated the longitudinal relationship between body mass index
      (BMI), a major vascular risk factor, and white matter lesions (WMLs) in older
      women. METHODS: Twenty-seven Swedish women were followed from age 70 to 88.
      Measurements of BMI, and systolic and diastolic blood pressures were conducted at
      70, 75, 79, 85, and 88 years. WMLs were measured using computerized tomography at
      age 85 and 88 (85/88). RESULTS: Women with any WMLs at age 85/88 had higher BMI
      at age 70 (p = 0.003) and 75 (p = 0.006), compared to women without WMLs.
      Increasing severity of WMLs was related to BMI at age 70 (p < 0.001), 75 (p <
      0.001), 79 (p = 0.017), and 85 (p = 0.025). After consideration of other vascular
      factors, BMI at age 70, 75, and 79 was most significantly related to WML at
      85/88. Every 1.0 kg/m2 increase in BMI at age 70 increased risk of WMLs twofold.
      CONCLUSIONS: Overweight and obesity may be important contributors to the presence
      of WMLs in the elderly.

PMID- 15559757
TI  - Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) in
      antipsychotic-naive Alzheimer's Disease patients.
AB  - BACKGROUND/OBJECTIVE: There were few studies identifying the natural unfolding of
      behavioural and psychological symptoms of dementia (BPSD) in the course of
      Alzheimer's disease (AD) progression in antipsychotic-naive AD patients. This
      study aims to examine the specific nature of the association between BPSD in AD
      and the global severity of illness measured by Global Deterioration Scale(GDS) in
      antipsychotic-naive AD patients in Korea. METHODS: A total of 562 antipsychotics
      naive AD patients were recruited from four different groups [a geriatric mental
      hospital (n = 145), a semi-hospitalized dementia institution (n = 120), a
      dementia clinic (n = 114) and community-dwelling dementia patients (n = 183)].
      BPSD exhibited by AD patients were measured using the 25-item Korean version of
      the BEHAVE-AD. RESULTS: Ninety-two percent (n = 517) of AD patients had at least
      one BPSD, while 56% (n=315) had 4 or more BPSD. Specific kinds of behavioral
      disturbance peak at the stages of moderate AD (GDS stage 5) or moderately severe
      AD (GDS stage 6). AD patients left at home without any treatment had higher
      frequency of BPSD than did other groups seeking treatment, although all of them
      were antipsychotic-naive. CONCLUSION: BPSD potentially remediable to treatment
      were highly frequent in Korean AD patients. Health policies to meet the unmet
      needs of elderly Koreans are urgently needed, especially for AD patients at home
      without treatment.

PMID- 15559758
TI  - The clinical and demographic characteristics of elderly patients of Polish origin
      newly referred to a geriatric psychiatry service.
AB  - OBJECTIVE: To compare the clinical, demographic, social and service utilization
      characteristics of elderly Poles with indigenous elders. SETTING: A geriatric
      psychiatry service in an urban area. METHODS: All newly referred patients to a
      West London geriatric psychiatry service were studied. The uptake of service and
      clinical, demographic, social and service utilization characteristics of elderly
      Poles and indigenous elders were compared after extracting information from case
      notes. RESULTS: Twelve percent of all referrals were of Polish origin. This
      figure is considerably higher than 4% of all community-dwelling elderly being of
      Polish origin in Ealing. There were no differences in clinical, demographic,
      social and service utilization characteristics between Polish and indigenous
      patients with a few exceptions. Elderly Poles were more likely to be married (p <
      0.005) and indigenous elders were more likely to be single (p < 0.05). Elderly
      Poles were more likely to be advised to take out power of attorney (p < 0.014).
      Elderly Poles were less fluent in English (p < 0.0005). CONCLUSIONS: Newly
      referred elderly Poles accessed and utilized the geriatric psychiatry service
      resources and social services at least as equitably as indigenous elders.

PMID- 15559759
TI  - The paper on reliability of the Geriatric Depression Scale (GDS) for use among
      elderly immigrants in the U.S.A. (Mui et. al., 2003).

PMID- 15559760
TI  - The ability of new sugar-modified derivatives of antitumor anthracycline,
      daunorubicin, to stimulate NAD(P)H oxidation in different cellular oxidoreductase
      systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine
      oxidase.
AB  - Numerous data indicate that cellular oxidoreductases may be responsible for the
      cardiotoxic effects of antitumor anthracycline drugs as a consequence of the
      mediation by these agents of one-electron transfer from reduced nucleotides to
      atmospheric oxygen. This process is catalyzed primarily by NADH dehydrogenase,
      NADPH cytochrome P450 reductase, and xanthine oxidase and leads to the formation
      of reactive oxygen species (ROS). In this work the data on the ability of new
      amino sugar derivatives of daunorubicin to stimulate NAD(P)H oxidation in the
      above oxidoreductase systems are presented. They represent analogues of
      daunorubicin in which the amino sugar nitrogen is bounded to an unsubsituted, or
      amino- or nitro-substituted benzyl group. It was found that the ability of
      examined sugar-modified derivatives of daunorubicin to stimulate NAD(P)H
      oxidation differs considerably depending on the subsituent in the phenyl ring. It
      was also determined that this ability was not identical in the three enzymatic
      systems studied, showing that these derivatives have different affinities for the
      enzymes examined. More similarities were observed in their interaction with NADH
      dehydrogenase and NADPH cytochrome P450 reductase than with xanthine oxidase.

PMID- 15559761
TI  - PAR1-type thrombin receptor stimulates migration and matrix adhesion of human
      colon carcinoma cells by a PKCepsilon-dependent mechanism.
AB  - The proteinase-activated receptor1 (PAR1) was characterized as a functional
      receptor for thrombin in cells from different tumor entities. In colon carcinoma,
      its function has to be defined. In this study we demonstrate that the PAR1
      selective agonist peptide TFLLRN induced activation of protein kinase C
      isoenzymes alpha and epsilon in human HT-29 colon carcinoma cells expressing PAR1
      endogeneously. On the cellular level, TFLLRN and thrombin prompted HT-29 cell
      migration and matrix adhesion by a PKCepsilon-dependent mechanism as concluded
      because of the inhibition of PAR1-mediated effects by the PKC inhibitor
      bisindolylmaleimide I and the PKCepsilon translocation inhibitory peptide
      EAVSLKPT but not by the PKC inhibitor Go 6976. In addition, blockade of PAR1 by
      RWJ 56110, a selective PAR1 antagonist, fully abolished the effect of thrombin on
      HT-29 cell migration and adhesion. Therefore, PAR1 seems to be the responsible
      receptor for thrombin-induced migration and adhesion of human colon carcinoma
      cells including PKCepsilon as an essential signal transducer.

PMID- 15559762
TI  - Nicotinamide relaxes vascular smooth muscle by inhibiting myosin light chain
      kinase-dependent signaling pathways: implications for anticancer efficacy.
AB  - Nicotinamide has been shown to be an effective tumor oxygenator in preclinical
      studies and is part of a promising clinical protocol for the treatment of cancer
      of the larynx. It has been known for some time that nicotinamide sensitizes
      tumors, at least in part, by modulating vascular smooth muscle contraction;
      however, the cellular target within the smooth muscle cell has yet to be
      identified. Our previous studies have eliminated targets within several agonist
      and antagonist signaling pathways in smooth muscle, suggesting that it must act
      at a point close to the contractile machinery of the cell. The present study
      investigated the effect of nicotinamide on four key steps responsible for force
      generation via actin/myosin interaction in the smooth muscle cell: calcium
      binding to calmodulin, calcium-calmodulin binding to smooth muscle myosin light
      chain kinase (MLCK) inhibitor peptide 480-501 (smMLCIP), modulation of MLCK
      dependent signaling, and MLCK-induced phosphorylation of the regulatory myosin
      light chain, MLC20. Nicotinamide abolished the phosphorylation of MLC20, but had
      no significant effect on the other endpoints tested. We conclude that the
      vasorelaxant effects of nicotinamide are mediated mainly through inhibition of
      MLC20 phosphorylation, and that this could be a promising target for the
      development of novel tumor oxygenators to enhance radio- and chemotherapy.

PMID- 15559763
TI  - The differential proteome profile of stomach cancer: identification of the
      biomarker candidates.
AB  - By comparative proteome analysis we searched for characteristic alterations of
      human stomach adenocarcinoma tissue and paired surrounding normal tissue.
      Selected differential protein spots were identified with peptide mass
      fingerprinting based on matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF) and database searching. We identified
      protein alterations in 18 stomach cancer tissues compared with normal controls,
      comprising elevated levels of eight proteins, including 14-3-3 zeta, calcyclin,
      keratin, apolipoprotein A-1 precursor, proteasome activator complex subunit,
      nucleoside diphosphate kinase, nicotinamide N-methyltransferase, and pyridoxal
      kinase. Five proteins (CA11, prohibitin, peroxiredoxin 4, serum amyloid P
      component, and NADH-ubiquinone oxidoreductase 23 kDa subunit) were decreased.
      These data are valuable for identification of differentially expressed proteins
      involved in stomach cancer carcinogenesis, providing biomarker candidates to
      develop diagnostic and therapeutic tools.

PMID- 15559764
TI  - Proteolysis of human plasma reveals the presence of complexes formed by
      endogenous heparin and peptides that stimulate angiogenesis.
AB  - Human endogenous plasma heparin associates with proteins that mask its
      anticoagulant activity. This association persists after exhaustive proteolysis of
      plasma, and resulting peptide/heparin complexes have no anticoagulant activity.
      Looking for functions other than inhibition of coagulation, we considered that
      commercial preparations of heparin from bovine or porcine sources show
      alternative effects on angiogenesis, either stimulating or inhibiting the
      process. However, the effects of endogenous human heparin on angiogenesis are
      unknown. In this study, the fraction of plasma containing endogenous heparin was
      prepared by means of exhaustive proteolysis, either in the presence or in the
      absence of 35S-labeled heparin. Plasma from healthy donors was digested and the
      supernatant was precipitated with 66% ethanol, dialyzed, and submitted to basic
      and acidic ion-exchange chromatography. 35S-Labeled heparin as well as endogenous
      heparin bound plasmatic peptides, forming acidic, basic, and neutral complexes.
      Binding of peptides, eluting from both resins, impaired migration of heparin on
      cellulose acetate electrophoresis. Endogenous neutral complexes (i.e., those
      formed by human endogenous plasma heparin and peptides) were tested for
      angiogenic activity in chick embryo chorioallantoic membrane assay. Bovine
      heparin induced a moderate angiogenic response. Neutral complexes of human
      endogenous plasma heparin and basic plasma peptides induced a very strong
      angiogenic response. Treatment of neutral complexes with nitrous acid, which
      degrades heparin, abolished the angiogenic effect, thus demonstrating that it was
      due to the presence of heparin. These results demonstrate that proteolysis of
      human plasma generates angiogenic peptide/heparin complexes.

PMID- 15559765
TI  - In vivo molecular pharmacology and antitumor activity of the targeted Akt
      inhibitor PX-316.
AB  - Akt, a serine/threonine kinase that promotes cell survival, is activated by
      binding of its pleckstrin homology (PH) domain to membrane phosphatidylinositol
      (PtdIns)-3-phosphates formed by PtdIns-3-kinase. D-3-Deoxy-phosphatidyl-myo
      inositols that cannot be phosphorylated on the 3-position of the myo-inositol
      group are inhibitors of the Akt PH domain. The most active compound is D-3-deoxy
      phosphatidyl-myo-inositol 1-[(R)-2-methoxy-3-octadecyloxypropyl hydrogen
      phosphate] (PX-316). PX-316 administered intraperitoneally to mice at 150 mg/kg
      inhibits Akt activation in HT-29 human tumor xenografts up to 78% at 10 h with
      recovery to 34% at 48 h. Phosphorylation of GSK-3beta, a downstream target of
      Akt, is also inhibited. There is no decrease in PtdIns(3,4,5)-trisphosphate
      levels by PX-316, showing it is not an inhibitor of PtdIns-3-K in vivo. Gene
      expression profiling of HT-29 tumor xenografts shows many similarities between
      the effects of PX-316 and the PtdIns-3-K inhibitor wortmannin, with
      downregulation of several ribosomal-related genes, while PX-316 uniquely
      increases the expression of a group of mitochondrial-related genes. PX-316 has
      antitumor activity against early human MCF-7 breast cancer and HT-29 colon cancer
      xenografts in mice. PX-316 formulated in 20% hydroxypropyl-beta-cyclodextrin for
      intravenous administration is well tolerated in mice and rats with no hemolysis
      and no hematological toxicity. Thus, PX-316 is the lead compound of a new class
      of potential agents that inhibit Akt survival signaling.

PMID- 15559766
TI  - A consultation, by any other name.
AB  - The decision to report a consultation code is based on a number of factors,
      including: the existence of a request from a physician or other authorized source
      for opinion or advice, documentation of the face-to-face patient encounter, and a
      written report of the findings, opinions or advice to the attending physician.
      Depending upon practice location, relationship with the referring physician
      population, number of self-referred patients, and other factors, some practices
      will report primarily consultation codes, whereas others may assign more codes
      for new patient visits.

PMID- 15559767
TI  - Navigating CoC's web resources.

PMID- 15559768
TI  - Strategic planning--executing the plan: how to ensure that real change occurs.

PMID- 15559769
TI  - Caring for the caregiver.

PMID- 15559770
TI  - Developing a comprehensive cancer center rehabilitation program.
AB  - As more oncology care is provided in the outpatient setting, cancer centers and
      oncology healthcare professionals are presented with greater opportunities to
      substantially enhance the quality of care given to patients. A diagnosis of
      cancer is a life-changing event that has many implications for the patient, as
      well as his or her family members. The stress of dealing with a new cancer
      diagnosis and the ensuing medical treatment can be overwhelming. Treatment for
      cancer may involve complex protocols, leaving patents mentally and physically
      exhausted. A multidisciplinary approach to the primary treatment plan-surgery,
      chemotherapy, and radiation therapy--is the standard of care. However, formalized
      rehabilitation programs for this patient population are unique. Many facilities
      rely on a centralized rehabilitation department within a medical center to meet
      the needs of oncology patients. Although this is the traditional approach, the
      growing complexity of cancer treatment provides an opportunity to enhance the
      rehabilitation process. The Gibbs Regional Cancer Center (GRCC), which is a part
      of Spartanburg Regional Healthcare System, teamed up with the hospital
      rehabilitation department to create a venue specifically designed for oncology
      patients. Described within this article is the developmental process of the GRCC
      Rehabilitation Program.

PMID- 15559771
TI  - Where are the leaders?

PMID- 15559772
TI  - A conversation with Rheba de Tornyay, EdD, RN, FAAN.

PMID- 15559773
TI  - Shaping a career trajectory in academic administration: leadership development
      for the deanship.
AB  - The nursing profession continues to face many challenges, one of which is an
      insufficient number of aspiring leaders. The role of an academic leader,
      specifically that of dean, brings with it unique challenges and opportunities.
      Shaping a career in academic administration requires careful consideration of the
      leadership skills necessary to perform in this complex and challenging role.
      However, it is critical to the future of nursing as a profession that ample
      numbers of aspiring leaders can successfully make this transition. One can be
      better prepared to take on this exciting and rewarding leadership opportunity
      when one understands the challenges deans face, asks questions such as "Do I
      really want a deanship?," identifies the required leadership skills, defines a
      career trajectory and pathway, and develops the leadership skills necessary for
      deans.

PMID- 15559774
TI  - Leading in a time of change: assuming interim academic administrator positions.
AB  - This article is about interim leadership in academic settings, specifically at
      the level of dean of an educational program in nursing. The interim administrator
      is often an invisible actor in the history of a school or department. However,
      they are key players in maintaining stability, facilitating change, and providing
      a transitional pathway for the new, permanent leader. An essential theme is that
      interim administrators do real work that has consequences, and make real
      contributions to institutional history and continuity. This article provides
      guidance to those considering or serving in interim positions. Guidelines are
      suggested for the stages of evaluating and serving in interim positions:
      assessing the request to serve, making a decision about accepting an interim
      position, negotiating an interim position, and acting out the interim position,
      using the analogy of a theatrical play and guideposts for actors.

PMID- 15559775
TI  - Building high-impact science: the dean as innovator.
AB  - If funding level is accepted as an empirical referent of research productivity,
      the nursing profession's relatively low volume of funded research puts its
      capacity to influence practice and policy based on scientific evidence at a
      disadvantage. For the profession to effectively compete with other "high-impact,"
      health-related disciplines, nursing leaders must find ways for a greater
      proportion of nursing faculty to excel as scientists, producing sufficient volume
      and quality of work in their careers to have a major influence on health care. In
      addition, if nursing leaders are to enhance nurses' interest in scientific
      development and use, the academic environment needs to foster greater
      connectivity of students at all levels of education with the scientific
      enterprise.

PMID- 15559776
TI  - Looking through the right end of the telescope: creating a focused vision for a
      school of nursing.
AB  - The challenges facing nursing higher education necessitate that academic
      administrators have a focused vision for their schools of nursing. Nursing, like
      other areas of higher education, embraced the concept of strategic planning to
      set priorities, use resources wisely, and take advantage of available
      opportunities that were consistent with the strategic direction. While there has
      been a shift toward a less-structured approach to planning, nursing deans need
      tools to assess the environment, make rational decisions, set priorities, plan
      for change, and develop strategies to meet the short-term and long-term goals of
      the unit. Given the challenges facing nursing education and higher education, the
      need for a planning approach is critical. The case study in this article
      describes a flexible and creative approach to the planning process that helped
      the University of Virginia School of Nursing set priorities and achieve its
      goals.

PMID- 15559777
TI  - Travel tips for a journey into academic administration.
AB  - A first-time administrator in a nursing academic setting can succeed in service
      to students and colleagues. To find the greatest personal contentment in this new
      role, the author suggests clarifying a personal purpose statement and becoming
      more self-aware. The author provides tips for finding exhilarating academic
      administration experiences in terms of association, action, and achievement.

PMID- 15559778
TI  - Building social capital: leading and leveraging constituencies outside the
      college.
AB  - Building social capital for a college and discipline requires actively engaging
      in the work of the university and creating partnerships with stakeholders outside
      the university, who share common areas of interest. As a public university dean
      for the past 5 years, I have found this work demands a considerable investment of
      time, energy, and stamina to maintain the vision of ultimate success. This
      article discusses three lessons I have learned in this journey as a new dean:
      serving as dean involves more than your college; a dean must actively engage in
      the work of the university as a whole and advocate for other colleges within the
      university; and a dean must take time to engage stakeholders outside the
      university.

PMID- 15559779
TI  - Faculty roles in supporting new deans and directors.
AB  - Although the topic is not frequently addressed in the literature, faculty members
      are influential in leadership transitions within colleges. New leaders are chosen
      for their experience; vision; and ability to work with faculty, students, staff,
      and upper-level administrators to clarify and implement their vision for academic
      departments, schools, or colleges. However, a degree of uncertainty is involved
      when people learn to work with each other. Faculty play an important role in
      facilitating interactions and enhancing leader success. This article describes
      strategies faculty can use during these transitions.

PMID- 15559780
TI  - Creating leadership skills in fundamental courses.

PMID- 15559781
TI  - Lumbar spinal fusion. Outcome in relation to surgical methods, choice of implant
      and postoperative rehabilitation.
AB  - Chronic low back pain (CLBP) has become one of the most common causes of
      disability in adults under 45 years of age and is consequently one of the most
      common reasons for early retirement in industrialised societies. Accordingly,
      CLBP represents an expensive drain on society's resources and is a very
      challenging area for which a consensus for rational therapy is yet to be
      established. The spinal fusion procedure was introduced as a treatment option for
      CLBP more than 70 years ago. However, few areas of spinal surgery have caused so
      much controversy as spinal fusion. The literature reveals divergent opinions
      about when fusion is indicated and how it should be performed. Furthermore, the
      significance of the role of postoperative rehabilitation following spinal fusion
      may be underestimated. There exists no consensus on the design of a program
      specific for rehabilitation. Ideally, for any given surgical procedure, it should
      be possible to identify not only possible complications relative to a surgical
      procedure, but also what symptoms may be expected, and what pain behaviour may be
      expected of a particular patient. The overall aims of the current studies were:
      1) to introduce patient-based functional outcome evaluation into spinal fusion
      treatment; 2) to evaluate radiological assessment of different spinal fusion
      procedures; 3) to investigate the effect of titanium versus stainless steel
      pedicle screws on mechanical fixation and bone ingrowth in lumbar spinal fusion;
      4) to analyse the clinical and radiological outcome of different lumbar spinal
      fusion techniques; 5) to evaluate complications and re-operation rates following
      different surgical procedures; and 6) to analyse the effect of different
      rehabilitation strategies for lumbar spinal fusion patients. The present thesis
      comprises 9 studies: 2 clinical retrospective studies, 1 clinical prospective
      case/reference study, 5 clinical randomised prospective studies and 1 animal
      study (Mini-pigs). In total, 594 patients were included in the investigation from
      1979 to 1999. Each had prior to inclusion at least 2 years of CLBP and had
      therefore been subjected to most of the conservative treatment leg pain, due to
      localized isthmic spondylolisthesis grades I-II or primary or secondary
      degeneration. PATIENT-BASED FUNCTIONAL OUTCOME: Patients' self-reported
      parameters should include the impact of CLBP on daily activity, work and leisure
      time activities, anxiety/depression, social interests and intensity of back and
      leg pain. Between 1993 and 2003 approximately 1400 lumbar spinal fusion patients
      completed the Dallas Pain Questionnaire under prospective design studies. In
      1996, the Low Back Pain Rating scale was added to the standard questionnaire
      packet distributed among spinal fusion patients. In our experience, these tools
      are valid instruments for clinical assessment of candidates for spinal fusion
      procedures. RADIOLOGICAL ASSESSMENT: It is extremely difficult to interpret
      radiographs of both lumbar posterolateral fusion and anterior interbody fusion.
      Plain radiographs are clearly not the perfect media for analysis of spinal
      fusion, but until new and better diagnostic methods are available for clinical
      use, radiographs will remain the golden standard. Therefore, the development of a
      detailed reliable radiographic classification system is highly desirable. The
      classification used in the present thesis for the evaluation of posteroalteral
      spinal fusion, both with and without instrumentation, demonstrated good
      interobserver and intraobserver agreement. The classification showed acceptable
      reliability and may be one way to improve interstudy and intrastudy correlation
      of radiologic outcomes after posterolateral spinal fusion. Radiology-based
      evaluation of anterior lumbar interbody fusion is further complicated when cages
      are employed. The use of different cage designs and materials makes it almost
      impossible to establish a standard radiological classification system for
      anterior fusions. BONE-SCREW INTERFACE: Mechanical binding at the bone-screw
      interface was significantly greater for titanium pedicle screws than it was for
      stainless steel. This could be explained by the fact that the titanium screws had
      superior bone on-growth. There was no correlation between screw removal torques
      and pull-out strength. Clinically, the use of titanium and titanium-alloy pedicle
      screws may be preferable for osteoporotic patients and those with decreased
      osteogenesis. OUTCOME: The present series of studies observed significant long
      term functional improvement for approximately 70% of patients who had undergone
      lumbar spinal fusion procedure. Solid fusion as determined from radiographs
      ranged from 52% to 92% depending on the choice of surgical procedure. The choice
      of surgical procedure should relate to the diagnosis, as patients with isthmic
      spondylolisthesis (Grades I and II) are best served with posterolateral fusion
      without instrumentation, and patients with disc degeneration seem to gain most
      from instrumented posterolateral fusion or circumferential fusion. COMPLICATIONS:
      The number of perioperative complications increased with the use of pedicle screw
      systems to support posterolateral fusions and increased further with the use of
      circumferential fusions. There was no significant association between outcome
      result and perioperative complications. The risk of reoperation within 2 years
      after the spinal fusion procedure was, however, significantly lower for those who
      had received circumferential fusion in comparison to posterolateral fusion with
      instrumentation. Furthermore, the risk of non-union was found to be significantly
      lower for patients who had received circumferential fusion as compared to
      posterolateral fusion with and without instrumentation. The complications of
      sexual dysfunction and fusion at non-intended levels were found to be significant
      but without influence on the overall outcome. REHABILITATION: The patients in the
      Back-cafe group performed a succession of many daily tasks significantly better
      and moreover had less pain compared with both the Video and Training groups 2
      years after lumbar spinal fusion. The Video group had significantly greater
      treatment demands outside the hospital system. This study demonstrates the
      importance of the inclusion of coping schemes and questions the role of intensive
      exercises in a rehabilitation program for spinal fusion patients.

PMID- 15559782
TI  - [A mismatch negativity elicited with stationary and moving auditory images of
      different azimuth positions].
AB  - Characteristics of mismatch negativity elicited by dichotic stimulation were
      examined using deviant stimuli simulating movement of fused auditory images
      towards the standard stimuli or in the reverse direction. The effect of
      stationary deviants localized at 90 degrees in respect to standards was also
      measured. The standard stimuli were localized near either of ears or along the
      head midline. The spatial locations were produced by introducing interaural time
      differences into the click trains. All deviant stimuli evoked the mismatch
      negativity. The deviants moving from standards seem to evoke the lowest mismatch
      negativity with the longest latency at all azimuthal locations of standard
      stimuli. Besides, the deviant shift from standards proved to be the only
      direction at which the characteristics of mismatch negativity depended upon the
      standard's azimuth. It is seems that the discrimination of interaural time delay
      is essentially dependent on the pattern of interaural delay changes at the moment
      when the deviant occurs.

PMID- 15559783
TI  - [The effects of electrical stimulation of posterior hypothalamus on activity of
      the nucleus pontis oralis' neurons].
AB  - The nucleus pontis oralis' neurons were responsive to electrical stimulation of
      posterior hypothalamus. PS-on neurons showed an inhibitory response, and PS-off
      cells demonstrated an excitatory response. Neurons that discharged in association
      with phasic paradoxical sleep phenomena were found to have both the excitatory
      and the inhibitory responses. Evoked responses changed across sleep-waking cycle.
      The findings suggest that posterior hypothalamus is involved in the control of
      paradoxical sleep generation mechanisms located in the nucleus pontis oralis.

PMID- 15559784
TI  - [Na+/H+ exchange inhibitors: a new class of cardioprotectors].
AB  - The Na+/H+ exchanger (NHE) extrudes intracellular H+ in exchange for Na+ in an
      electroneutral process. Of the 6 mammalian exchanger isoforms identified to date,
      the NHE-1 is believed to be the molecular homologue of the sarcolemma Na+/H+
      transporter. The exchanger is activated primarily by a reduction in intracellular
      pH, although such activation is subject to modulation by a variety of endogenous
      mediators (catecholamines, thrombin, endothelin) through receptor-mediated
      mechanisms. A large body of animal studies using both in vitro and in vivo models
      indicates that the inhibition of the sarcolemma NHE-1 attenuates myocardial
      injury in ischemia and reperfusion. Cardioprotective effects of NHE-1 inhibition
      involve a reduced susceptibility to severe ventricular arrhythmia, augmentation
      of contractile function recovery, and limitation of infarction size during
      reperfusion. Such protection is likely to arise partly from attenuation of "Ca2+
      overload" in ischemic cardiomyocytes, which has been causally linked with all
      these pathologic phenomena. A marked benefit that has been observed with
      cariporide (HOE-642) and its structurally related congener HOE-694 in patients
      with acute myocardial infarction and in cardiac surgery demonstrates that
      selective NHE-1 inhibitors represent a novel and effective class of
      cardioprotectors.

PMID- 15559785
TI  - [Influence of He-Ne laser irradiation and local anesthetics on potassium channels
      in the snail neurons].
AB  - Using clamp method it had been shown that He-Ne laser irradiation of the snail
      neurons increases the amplitude of voltage-gated slow potassium currents in dose
      of 0.7 x 10(-4) (fluence 1.5 x 10(2) Wt/m2) and decreases it in dose 0.7 x 10(
      3). Bupivacaine and lidocaine suppressed potassium currents. Laser irradiation in
      dose 0.7 x 10(-3) enhanced the inhibitory effect of bupivacaine (10 mcM) and in
      dose 0.7 x 10(-4) it decreased the inhibitory effect of bupivacaine. The results
      of the study suggest mechanisms of the He-Ne laser irradiation effect in
      combination with pharmacological substances on ion channels of electrically
      excitable cells.

PMID- 15559786
TI  - [Restoration of blood rheological properties by means of SWF-irradiation at the
      frequency of nitric oxide molecular spectrum (in vivo)].
AB  - We have investigated impact of electromagnetic SWF-oscillations at nitric oxide
      molecular spectrum of radiation and absorption (MSRA) on rheological blood
      properties of albino rats under the immobilizing stress. The SWF-irradiation was
      demonstrated to foster restoration of disordered rheological blood properties,
      its efficiency depending on the period of irradiation.

PMID- 15559787
TI  - [Leukocyte adhesion to walls of the rat pial venules in normoxia and during brain
      ischemia].
AB  - With the help of contact optic system direct observations were carried out on
      leukocyte movements and on the acts of their adhesion to the inner surface of the
      walls of pial venules of the rats in normoxia and ischemia resulting from
      ligating two carotid arteries. After ligating the carotid artery and subsequent
      gradual development of ischemia, an abrupt increase in the number of the acts of
      adhesion to the walls of pial venules was shown to occur, the leukocytes adhere
      to each other inside the venules. A complete occlusion of venules and small veins
      results, which can be one of the reasons for the animal death in brain ischemia.

PMID- 15559788
TI  - [Myocardial ischemic postconditioning: a brief ischemia causes conversion of
      resistent reperfusion-induced ventricular fibrillation into the normal rhythm].
AB  - Brief episodes of myocardial ischemia-reperfusion were shown to be protective
      against reperfusion injury when used during early reperfusion after a prolonged
      ischemic episode. This phenomenon has been termed myocardial ischemic
      postconditioning. In this study, an effect of ischemic postconditioning on
      persistent reperfusion-induced ventricular fibrillation was studied in the rat
      isolated heart. 2 minutes of global ischemia on the 15th minute of reperfusion
      after 30 minutes of regional ischemia effectively abolished the persistent
      ventricular fibrillation. In non-postconditioned hearts, the ventricular
      fibrillation continued to the end of reperfusion. The ischemic postconditioning
      seems to exert a strong antiarrhythmic effect protecting the heart against
      persistent reperfusion-induced ventricular tachyarrhythmias.

PMID- 15559789
TI  - [Responses of isolated arterial segment to a slow changing of perfusion pressure
      in it].
AB  - In in vitro experiments, segments of the Wistar rat tail artery's segments were
      perfused with the Krebs-Henselite solution. Increase of the perfusion pressure
      with the velocity of 5 mm Hg/min from 0 to 110 mm Hg with its subsequent drop
      with the same velocity down to zero showed that, within the limits of the above
      interval of values of the intravascular pressure, existed a range where two
      values of the artery diameter corresponded to each established value of the
      pressure. The data obtained prompt a further deciphering of mechanisms of the
      mechanogenic regulation of the blood vessels.

PMID- 15559790
TI  - [Influence of acute hemorrhage on erythrodieresis].
AB  - Influence of acute hemorrhage on peritoneal and splenic macrophages function and
      NO production was studied. Interaction of peritoneal and splenic macrophages with
      autologous erythrocytes was examined the day after the hemorrhage. Concentration
      of nitrate ions: the stable metabolites of nitric oxide, was measured in
      peritoneal lavage, splenic cells suspension, blood, as well as in supernatant of
      peritoneal and splenic macrophages before and after hemorrhage. The data obtained
      suggest that splenic macrophages of intact rats are more active than peritoneal
      ones. After hemorrhage peritoneal macrophages activity increases, whereas splenic
      macrophages remain unchanged. Concentration of nitrate ions is significantly
      reduced after hemorrhage.

PMID- 15559791
TI  - [Dynamics of the blood supply in the leg soft tissue in the course of
      experimental defect filling].
AB  - Hemodynamics in the leg soft tissues during bone regeneration in the diaphyseal
      defects separated from surrounding paraosseous tissues, was studied
      experimentally using 10 adult mongrel dogs. It has been established, that
      circulation changes occur both in the operated limb and in the contralateral
      limb. They are most obvious in the operated leg and have a phase character
      corresponding to posttraumatic period. Restoration of blood flow parameters
      starts just from the 28th day of the experiment, the parameters become completely
      stabilized by the end of the experiment (90 days). Bone regeneration in tibial
      defects is accompanied by circulation increase in the respective limb segment.

PMID- 15559792
TI  - [Dynamics of hypothalamic CRH immune reactivity in active and passive rats in the
      course of development of behavioural depression].
AB  - A possible relation between activity of the main CRH-producing centers of
      hypothalamus and depressive-like behavior of animals was studied. We used
      genetically selected strains--KHA (Koltushi High Avoidance) and KLA (Koltushi Low
      Avoidance) rats, demonstrating active and passive strategy of adaptive behavior
      in novelty situaltions, respectively. Rats were exposed to inescapable stress to
      develop a "learned helplessness". We observed considerable differences between
      two strains of animals in CRH-expression in parvo-, magno-cellular parts of the
      paraventricular nucleus and in the supraoptic nucleus in the course of behavioral
      depression development. Significant differences between control groups were seen
      only in paraventricular nucleus. On the 1st post-stress day in hypothalamus of
      KLA rats, we detected decreased CRH immune reactivity that remained unchanged up
      to the 10th day. In KHA rats, there were no notable changes of CRH expression in
      all studied nuclei. These findings, including previous results on different
      dynamics of behavioral changes and different hypothalamo-pituitary-adrenocortical
      system activity during development of depression in KLA and KHA rats, indicate
      that "learned helplessness" in these two groups of animals provides the model
      analogues of different types of depression. Besides, these findings indicate
      different implication of hypothalamus CRH-system in the behavioral depression
      development in rats with divergent strategy of adaptive behavior.

PMID- 15559793
TI  - [Overproduction of agouti-protein did not affect cAMP level but increased
      steroidogenesis in adrenal glands under forskolin stimulation].
AB  - Mutation Agouti yellow (Ay) in mice Ay/a results in overproduction of agouti
      protein (AP), adult onset of obesity, increased corticosterone responses to
      restrain stress as compared with a/a mice (absence of AP). The enhanced
      corticosterone response in restrained Ay/a-mice compared with restrained a/a-mice
      occurred in result of increased adrenal reactivity to ACTH. The purpose of this
      work was to investigate the influence of AP overproduction on adenylate cyclase
      (AC) activity and steroidogenesis in forskolin stimulated adrenal cells. To
      estimate obesity influence, these parameters were measured in young (3 weeks) and
      adult (15 weeks) animals. The data obtained demonstrated that AP overproduction
      and the obesity did not affect the AC activity. However, forskolin stimulated
      corticosterone production in Ay/a-mice was higher than in a/a-mice (in young-
      during 0.5 h, in adult--during 3 hrs of incubation). So AP overproduction and
      obesity affect the corticosterone production. We hypothesize that AP
      overproduction affects steroidogenesis gene expression: accelerates gene
      activation in ontogenesis and increases enzyme de novo synthesis during long-term
      stimulation in adults.

PMID- 15559794
TI  - [The symbiont digestion in the rabbit stomach].

PMID- 15559795
TI  - [Goltz Fridrich Leopold (on the 170th anniversary)].

PMID- 15559796
TI  - Emission control for precursors causing acid rain (V): Improvement of acid soil
      with the bio-briquette combustion ash.
AB  - The bio-briquette technique which mixes coal, biomass and sulfur fixation agent
      and bio-briquettes under 3-5 t/cm2 line pressure has aroused people's attention
      in view of controlling the air pollution and the acid rain. In this paper, the
      physicochemical properties of bio-briquette and its ash were investigated. And
      the acid soil was improved by the bio-briquette combustion ash, which contained
      nutritive substances such as P, N, K and had the acid-neutralizing capacity
      (ANC). The pH, EC, effective nutrient elements (Ca, Mg, K, P and N), heavy metal
      elements (Al, Cu, Cd, Cr, Zn and Mn) and acid-neutralizing capacity change of ash
      added soils within the range of 0-10%, were also studied. Specially, when 5% bio
      briquette combustion ash was added to the tested soil, the content of the
      effective elements such as Ca, Mg and K rose by 100 times, 7 times and twice,
      respectively. The total nitrogen also increased by about twice. The results
      showed the oxyanions such as that of Al, Cu, Cd, Cr, Zn and Mn were not
      potentially dangerous, because they were about the same as the averages of them
      in Chinese soil. It is shown that the ANC became stronger, though the ANC hardly
      increases in the ash-added soil. On the basis of the evaluation indices, it is
      concluded that the best mixture ratio is to add 2.5%-8% of the bio-briquette
      combustion ash to the tested soil.

PMID- 15559797
TI  - Relationship between AtPase activity and conjugated polyamines in mitochondrial
      membrane from wheat seedling roots under osmotic stress.
AB  - The effects of osmotic stress on the ATPase activity, the contents of -SH group
      and conjugated polyamines in mitochondrial membrane from wheat seedling [Triticum
      aestivum L. cv. Yumai No. 18 (drought-tolerant) and cv. Yumai No. 9 (drought
      sensitive)] roots were investigated. The results showed that ATPase activity and 
      SH group content decreased with polyethylene glycol(PEG) 6000(-0.55 MPa)
      treatment for 7 d, in concert with the decrease of the ratio of noncovalently
      conjugated spermidine (NCC-Spd)/noncovalently conjugated putrescine(NCC-Put) and
      increase of the covalently conjugated putrescine (CC-Put). Osmotic stress injury
      to Yangmai No.9 seedlings was alleviated greatly with 1 mmol/L exogenous
      spermidine(Spd), in concert with marked increases of the ratio of NCC-Spd/NCC
      Put, -SH group contents and ATPase activity in mitochondrial membrane. Under
      osmotic stress, the concomitant treatment of Yumai No. 18 seedlings with
      methylglyoxyl bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosyl methionine
      decarboxylase(SAMDC), and phenanthrolin (o-Phen), an inhibitor of
      transglutaminase(TGase), caused a significant decrease of the ratio of NCC
      Spd/NCC-Put, CC-Put contents, respectively, in concert with the marked decreases
      of ATPase activity, -SH group content and its tolerance to osmotic stress. All
      the results above suggested that osmotic stress tolerance of wheat seedlings was
      associated with the ATPase activity, the contents of -SH group, NCC-Spd and CC
      Put in mitochondrial membrane.

PMID- 15559798
TI  - Residue analysis and dissipation of monosulfuron in soil and wheat.
AB  - HPL-UV residue analytical method for monosulfuron [N-[(4'-methyl) pyrimidin-2'yl]
      2-nitrophenylsulfonyl urea] in soil and wheat was developed. Monosulfuron
      residues were recovered by solvent extraction, followed by liquid-liquid
      partition, and C18 cartrige clean-up. Excellent method recoveries ranging from
      95%-104% for both fortified soil and wheat grain were obtained with coefficients
      of variation 1.5%-11.8%. The minimum detectable quantities in soil and wheat were
      both 4 ng, the limit of detection was 0.02 mg/kg. When monosulfuron was applied
      according to double dosage of maximum recommended use direction(120 g ai/hm2 of
      10% monosulfuron wettable powder sprayed for once during development of wheat) in
      field studies conducted in Shandong Province and near Beijing, monosulfuron
      residues was not detected in soil and wheat samples collected 75 d after
      application. Laboratory soil degradation studies showed that monosulfuron
      degraded faster in acidic soil and strong alkaline soil than in neutral or weak
      alkaline soil. Half lives in Jiangxi soil, Shijiazhuang soil, Jiangsu soil and
      Heilongjiang soil were 41, 48, 87 and 84 d respectively. Monosulfuron residues
      dissipated rapidly in Shandong and Beijing field test sites with half-lives of
      less than 14 d.

PMID- 15559799
TI  - Streamwater chemistry and flow dynamics along vegetation-soil gradient in a
      subalpine Abies fabri forest watershed, China.
AB  - Streamwater chemistry and spatial flow dynamics from a subalpine Abies fabri
      forest in an experimental watershed located in the east slope of Gongga Mountain
      were analyzed to gain insights into the gradient effect of primary community
      succession on the stream biogeochemical process. Results showed that high sand
      content (exceeding 80%) and porosity in the soil(exceeding 20% in A horizon and
      35% in B horizon), as well as a thick humus layer on the soil surface, made the
      water exchange quickly in the Huangbengliu (HBL) watershed. Consequently, no
      surface runoff was observed, and the stream discharge changed rapidly with the
      daily precipitation. The flow trends of base ions in the stream water were
      influenced by the Abies fabri succession gradient. Ca2+ , HCO- and SO4(2-) were
      the dominant anions in the streamwater in this region. A significant difference
      of Ca2+, HCO3(-) and SO4(2-) concentration exported between the succession stages
      in the watershed can be found. But they had the similar temporal change in the
      stream flow. Ca2+, HCO3(-) and SO4(2-) showed significantly negative correlations
      with the daily precipitation and the stream discharge. Concentrations of Cl-,
      Na+, K+, and Mg2+ were low in all streamwaters monitored and we observed no
      differences along the Abies fabri succession gradient. Low ratios of Na: (Na +
      Ca) (range from 0.1 to 0.2) implied cations were from bedrock weathering
      (internal source process in the soil system) in this region. But, a variance
      analysis showed there were almost no differences between rainwater and
      streamwaters for Mg2+ , Na+, K+, and Cl- concentrations. This indicated that they
      might be come from rainfall inputs(external source). The highly mobile capacity,
      rapid water exchange between precipitation and discharge, and long-term export
      lead to this observed pattern were suggested.

PMID- 15559800
TI  - Accumulation of heavy metals in four grasses grown on lead and zinc mine
      tailings.
AB  - A field experiment was conducted to compare the growth and metal accumulation of
      Vetiveria zizanioides, Paspalum notatum, Cynodon dactylon and Imperata cylindraca
      var. major on the tailings, amended with 10 cm domestic refuse + complex NPK
      fertilizer(Treatment A), 10 cm domestic refuse(Treatment B) and complex NPK
      fertilizer (Treatment C) respectively, and without any amendment used as control
      (Treatment D). The results indicated that V. zizanioides was a typical heavy
      metal excluder, because the concentrations in shoots of the plants were the
      lowest among the four plants tested. The most of metal accumulated in V.
      zizanioides distributed in its root, and transportation of metal in this plant
      from root to shoot was restricted. Therefore, V. zizanioides was more suitable
      for phytostabilization of toxic mined lands than P. notatum and C. dactylon,
      which accumulated a relatively high level of metals in their shoots and roots. It
      was also found that I. cylindraca var. major accumulated lower amounts of Pb, Zn
      and Cu than C. dactylon and P. notatum, and could also be considered for
      phytostalilisaton of tailings. Although the metal(Pb, Zn and Cu) concentrations
      in shoots and roots of V. zizanioides were the lowest, the total amounts of heavy
      metals accumulated in shoots of V. zizanioides were the highest among the four
      tested plants due to the highest dry weight yield of it. The results indicated
      that V. zizanioides was the best choice among the four species used for
      phytoremediation (for both phytostabilization and phytoextraction) of metal
      contaminated soils.

PMID- 15559801
TI  - N2:O emissions from a cultivated Andisol after application of nitrogen
      fertilizers with or without nitrification inhibitor under soil moisture regime.
AB  - The aim of this work was to examine the emission of N2O from soils following
      addition of nitrogen fertilizer with a nitrification inhibitor (+inh) or without
      the nitrification inhibitor(-inh) at different soil water regime. Higher soil
      moisture contents increased the total N2O emissions in all treatments with total
      emissions being 7 times larger for the CK and > 20 times larger for the
      fertilizer treatments at 85% WFPS (soil water filled pore space) than at 40%
      WFPS. The rates of N2O emissions at 40% WFPS under all treatments were small. The
      maximum emission rate at 55% WFPS without the nitrification inhibitor (-inh)
      occurred later (day 11) than those of 70% WFPS (-inh) samples (day 8). The
      inhibition period was 4-22 d for 55% WFPS and 1-15 d for 70% WFPS comparing the
      rates of N2O emissions treated (+inh) with (-inh). The maximum emission rates at
      85% WFPS were higher than those at the other levels of soil water content for all
      treatments. The samples (+inh) released less N2O than (-inh) samples at the early
      stage. Nevertheless, N2O emissions from (+inh) samples lasted longer than in the
      (-inh) treatment. Changes in mineral N at 55%, 70% and 85% WFPS followed the same
      pattern. NH4(+) -N concentrations decreased while NO3(-) -N concentrations
      increased from the beginning of incubation. NH4(+) -N concentrations from 40%
      WFPS treatment declined more slowly than those of the other three levels of soil
      water content. Nitrification was faster in the (-inh) samples with 100% NH4(+) -N
      nitrified after 22 d (50% WFPS) and 15 d (70% and 85% WFPS). N2O emissions
      increased with soil water content. Adding N-fertilizer increased emissions of
      N2O. The application of the nitrification inhibitor significantly reduced total
      N2O emissions from 30.5% (at 85% WFPS) to 43.6% (at 55% WFPS).

PMID- 15559802
TI  - Adsorption of phenthoate and acetochlor from water by clays and organoclays.
AB  - Adsorption of phenthoate and acetochlor onto kaolin, montmorillonite, bentonite
      clays and respective organoclays prepared by the exchange of quaternary ammonium
      as tetradecyltrimethyl ammonium bromide(TTAB), dodecyltrimethylammonium bromide
      (DTAB), and cetylpyridinium chloride (CPC) were studied. The adsorption
      equilibrium data points were fitted to Freundlich isotherm equations. The
      adsorption of phenthoate and acetochlor were significantly enhanced by surfactant
      treatment of the clays. The amount of both pesticides adsorbed per unit mass of
      organoclay followed the order of TTA-kaolin < TTA-montmorillonite < TTA
      bentonite, which is inconsistent with the organic carbon content of the clays.
      The removal efficiency of organomontmorillonite to treat acetochlor is in the
      order of CP (C16)-montmorillonite > TTA (C14)-montmorillonite > DTA (C12)
      montmorillonite. Phenthoate is adsorbed to greater extent than acetochlor by each
      adsorbent, which may be due to the higher hydrophobicity of phenthoate,
      indicating considerable hydrophobic interaction between adsorbent/adsorbate
      systems.

PMID- 15559803
TI  - Changes of plasma membrane AtPase activity, membrane potential and transmembrane
      proton gradient in Kandelia candel and Avicennia marina seedlings with various
      salinities.
AB  - The salt-secreting mangrove, Avicennia marina, and non-salt-secreting mangrove,
      Kandelia candel were cultivated in sand with various salinities(0 per thousand,
      10 per thousand, 20 per thousand, 30 per thousand, 40 per thousand) for 60 d.
      Plasma membrane vesicles of high-purity in leaves and roots of A. marina and K.
      candel seedlings were obtained by two-phase partitioning. The function of the
      plasma membranes, the activity of ATPase, membrane potential and transmembrane
      proton gradient, at various salinities were investigated. The results showed that
      within a certain range of salinity (A. marina and roots of K. candel: 0-30 per
      thousand; leaves of K. candel: 0-20 per thousand), the activity of ATPase
      increased with increasing salinity, while high salinity (above 30 per thousand or
      20 per thousand) inhibited ATPase activity. In comparison with A. marina, K.
      candel appeared to be more sensitive to salinity. The dynamics of membrane
      potential and transmembrane proton gradient in leaves and roots of A. marina and
      K. candel seedlings were similar to that of ATPase. When treated directly by NaCl
      all the indexes were inhibited markedly: there was a little increase within 0-10
      per thousand (K. candel) or 0-20 per thousand (A. marina) followed by sharp
      declining. It indicated that the structure and function of plasma membrane was
      damaged severely.

PMID- 15559804
TI  - Full-scale study of removal effect on Cyclops of zooplankton with chlorine
      dioxide.
AB  - Cyclops of zooplankton propagated excessively in eutrophic water body and could
      not be effectively inactivated by the conventional disinfections process like
      chlorination due to its stronger resistance to oxidation. In this paper, a full
      scale study of chlorine dioxide preoxidation cooperating with routine
      clarification process for Cyclops removal was conducted in a waterworks. The
      experimental results were compared with that of the existing prechlorination
      process in several aspects: including the Cyclops removal efficiencies of water
      samples taken from the outlets of sedimentation tank and sand filter and the
      security of drinking water and so on. The results showed that chlorine dioxide
      might be more effective to inactivate Cyclops than chlorine and Cyclops could be
      thoroughly removed from water by pre-dosing chlorine dioxide process. The GC-MS
      examination and Ames test further showed that the sort and amount of organic
      substance in the treated water by chlorine dioxide preoxidation were evidently
      less than that of prechlorination and the mutagenicity of drinking water treated
      by pre-dosing chlorine dioxide was substantially reduced compared with
      prechlorination.

PMID- 15559805
TI  - An assessment of the concentrations of particulate polycyclic aromatic
      hydrocarbons (PAHs) in the aftermath of a chemical store fire incident.
AB  - PM10 airborne particles and soot deposit collected after a fire incident at a
      chemical store were analyzed in order to determine the concentrations of
      polycyclic aromatic hydrocarbons (PAHs). The samples were extracted with 1:1
      hexane-dichloromethane by ultrasonic agitation. The extracts were then subjected
      to gas chromatography-mass spectrometric (GC-MS) analysis. The total PAHs
      concentrations in airborne particles and soot deposit were found to be 3.27 +/-
      1.55 ng/m3 and 12.81 +/- 24.37 microg/g, respectively. Based on the molecular
      distributions of PAHs and the interpretation of their diagnostic ratios such as
      PHEN/(PHEN + ANTH), FLT/(FLT + PYR) and BeP/(BeP + BaP), PAHs in both airborne
      particles and soot deposit may be inferred to be from the same source. The
      difference in the value of IP/(IP + BgP) for these samples indicated that
      benzo[g, h, i] perylene and coronene tend to be attached to finer particles and
      reside in the air for longer periods. Comparison between the molecular
      distributions of PAHs and their diagnostic ratios observed in the current study
      with those reported for urban atmospheric and roadside soil particles revealed
      that they are of different sources.

PMID- 15559806
TI  - [Ecological service assessment of human-dominated freshwater ecosystem with a
      case study in Yangzhou Prefecture, China.
AB  - Freshwater ecosystems provide a host of services to humanity. These services are
      now rapidly being lost, not least because of the inability of making the impacts
      measurable. To overcome this obstacle, assessment frameworks for freshwater
      ecosystem services are needed. A simple water equivalent framework to assess the
      ecological services provided by freshwater ecosystems was developed in this
      study. It translated the occupation of freshwater ecosystem services into
      biologically freshwater volumes and then compares this consumption to the
      freshwater throughput, that is, the ecological capacity available in this region.
      In this way, we use the example of Yangzhou Prefecture, to account the main
      categories of human occupation of water ecosystem services. The result showed
      that there is a huge gap between the consumption and the supply of freshwater
      ecosystem services. This must encourage local government to make land-use and
      water management decisions both economically rational and environmentally sound.

PMID- 15559807
TI  - Experimental study on pollutant movement in surf zone.
AB  - The experiments on pollutant movement in surf zone were conducted on the two
      gentle beaches (with slope of 1:100 and 1:40, respectively), for diverse wave
      cases. The movement contours and direction of pollutants, under the action of
      regular and random waves with diverse wave amplitudes, were provided and studied
      in this paper. It was shown that, due to complicated hydrodynamics in surf zone,
      the pollutant movement state is quite complicated and different from that in pure
      current zone.

PMID- 15559808
TI  - Scenario simulation of water security in China.
AB  - Limited water resources, increasing demand, low use efficiency, and serious
      pollution result in severe water resource difficult in China. The evaluation of
      addressing water problems and the search for effective countermeasures that
      ensure sustainable water use are key to China's sustainable development. The
      "compound water security" consists of food security, life security, environmental
      security, and economic security. By establishing a conceptual model, the water
      security of China has been simulated in terms of four scenarios called BAU (the
      business-as-usual scenario), TEC (the technology and economics scenario), IVL
      (the institution, values, and lifestyles scenario) and TSD(toward sustainable
      development) in this paper. The results indicated that water crises, especially
      water shortages, are being experienced now and will continue to do so for a
      relatively long time in China and that it is possible to reach a basic balance
      between supply and demand of water and grain under the TSD developing pattern by
      a series of approaches including technological innovation, policy adjustments,
      and behaviour inducement.

PMID- 15559809
TI  - Toxicity of cypermethrin to Daphnia magna HB.
AB  - The acute toxic effect of the pesticide cypermethrin to Daphnia magna HB was
      examined. D. magna HB was exposed to cypermethrin at concentrations of 0, 1, 3,
      5, 7, and 9 mg/L for 24 h. Data showed that the 24 h-LC50 of cypermthrin on D.
      magna HB was 4.81 mg/L. In contrast, the 24 h-LC50 of K2Cr2O7 (the national
      standard toxicant) to Daphnia magna was 0.38 mg/L in the current study. Results
      indicated that the Daphnia magna was very sensitive to pesticides. In addition,
      the effects of the culture condition (such as hardness, temperature and DO etc.)
      on Daphnia magna HB was also studied.

PMID- 15559810
TI  - Succession of aquatic microbial communities as a result of the water quality
      variations in continuous water.
AB  - The changes of structural and functional parameters of aquatic microbial
      communities in continuous water on campus of Tsinghua University, China are
      investigated, by polyurethane foam unit (PFU) method. The measured compositions
      of the communities include alga, protozoa, and some metazoa (such as rotifers).
      The measured indicators of water quality include water temperature, pH value,
      dissolved oxygen (DO), potassium permanganate index (COD(Mn)), total nitrogen
      (TN), total phosphorus (TP) and chlorophyll-a (Chla). The trophic level,
      expressed by the trophic level indices (TLIc), is assessed with analytic
      hierarchy process and principal component analysis (AHP-PCA) method. The changing
      trends of the structural and functional parameters of aquatic microbial
      communities, such as Margalef index of diversity (D), Shannon-weaver index of
      diversity (H), Heterotropy index (HI), number of species when the colonization
      gets equilibrium (S(eq)), colonizing speed constant (G) and time spent when 90
      percent of S(eq) colonized in PFU (T(80%)), are also analyzed. The experimental
      results showed the succession of aquatic microbial communities along the water
      flow is consistent with the water quality changes, so the parameters of microbial
      community can reflect the changes of water quality from the ecological view.

PMID- 15559811
TI  - Interannual variability of carbon cycle implied by a 2-d atmospheric transport
      model.
AB  - A 2-dimensional atmospheric transport model is deployed in a simplified CO2
      inverse study. Calculated carbon flux distribution for the interval from 1981 to
      1997 confirms the existence of a terrestrial carbon sink in mid-high latitude
      area of North Hemisphere. Strong interannual variability exists in carbon flux
      patterns, implying a possible link with ENSO and other natural episodes such as
      Pinatubo volcano eruption in 1991. Mechanism of this possible link was
      investigated with statistic method. Correlation analysis indicated that in North
      Hemisphere, climatic factors such as temperature and precipitation, to some
      extend, could influence the carbon cycle process of land and ocean, thus cause
      considerable change in carbon flux distribution. In addition, correlation study
      also demonstrated the possible, important role of Asian terrestrial ecosystems in
      carbon cycle.

PMID- 15559812
TI  - Endocrine disrupting effects on Chinese rare minnow (Gobiocypris rarus) fed with
      field collected Limnodrilus sp.
AB  - The potential endocrine disrupting effects and other toxicity effects on aquatic
      biota resulted from food uptake was simulated by feeding the laboratory cultured
      rare minnow( Gobiocypris rarus) with field collected Limnodrilus sp. The results
      indicated that the food chain processes affected significantly the growth,
      slightly reduced gonadosomatic indices, and elevated hepatosomatic indices. There
      was an obvious vitellogenin(VTG) induction, which generally only occurred in
      mature female, in the serum of juvenile rare minnow and mature male when fed with
      Limnodrilus sp. In addition, the rare minnow feeding on Limnodrilus sp. had
      significantly high renal indices, it meant obvious renal hyperplasia. The present
      work suggested that Limnodrilus sp. from field water may contain toxic pollutants
      and could lead to endocrine disruption effects to the predators. It was concluded
      that endocrine disruptors may not only be assimilated through water, but also be
      bioconcentrated through food web. The results also suggested the importance of
      food selection in conducting the study of endocrine disruption effects using
      sensitive species.

PMID- 15559813
TI  - Effect of substrate concentration on the bioleaching of heavy metals from sewage
      sludge.
AB  - The effect of elemental sulfur concentration on bioleaching of Cu, Zn and Pb and
      loss of fertilizer value from sewage sludge was investigated in flasks by batch
      experiments. The results showed that the ultimate pH of sludges with 3-5 g/L of
      sulfur added was about 1.3 and the production of SO4(2-) had good correlation
      with the elemental sulfur concentration. The sensitivity of removal efficiency of
      metals to sulfur concentration was: Pb > Cu > Zn. The sulfur concentration except
      for 3-5 g/L had significant effect on the solubilization of Cu, Pb and Zn. The
      highest solubilization efficiency for sludge with 3 g/L of sulfur was 87.86% for
      Cu, 32.72% for Pb and 92.14% for Zn, which could make the treated sludge easily
      meet the metal limitations for land application. The sulfur concentration of 3
      g/L was enough for the solubilization of all three heavy metals. The influence of
      sulfur concentration on solubilization of total nitrogen and potassium from
      sludge was negligible, but that on solublization of total phosphorus was of great
      importance. The loss of nitrogen, phosphorus and potassium of sludge with 3 g/L
      of sulfur by bioleaching was 38.2%, 52.1% and 42.8% respectively, and the sludge
      still remained satisfactory fertilizer value after bioleaching.

PMID- 15559814
TI  - Preparation and emission characteristics of ethanol-diesel fuel blends.
AB  - The preparation of ethanol-diesel fuel blends and their emission characteristics
      were investigated. Results showed the absolute ethanol can dissolve in diesel
      fuel at an arbitrary ratio and a small quantity of water(0.2%) addition can lead
      to the phase separation of blends. An organic additive was synthesized and it can
      develop the ability of resistance to water and maintain the stability of ethanol
      diesel-trace amounts of water system. The emission characteristics of 10%, 20%,
      and 30% ethanol-diesel fuel blends, with or without additives, were compared with
      those of diesel fuel in a direct injection (DI) diesel engine. The experimental
      results indicated that the blend of ethanol with diesel fuel significantly
      reduced the concentrations of smoke, hydrocarbon (HC), and carbon monoxide (CO)
      in exhaust gas. Using 20% ethanol-diesel fuel blend with the additive of 2% of
      the total volume, the optimum mixing ratio was achieved, at which the bench
      diesel engine testing showed a significant decrease in exhaust gas. Bosch smoke
      number was reduced by 55%, HC emission by 70%, and CO emission by 45%, at 13
      kW/1540 r/min. However, ethanol-diesel fuel blends produced a few ppm
      acetaldehydes and more ethanol in exhaust gas.

PMID- 15559815
TI  - Experimental study on Cr (V) reduction by Pseudomonas aeruginosa.
AB  - Investigation on Cr(V) reduction was conducted using Pseudomonas aeruginosa. The
      study demonstrated that the Cr(VI) can be effectively reduced to Cr(III) by
      Pseudomonas aeruginosa. The effects of the factors affecting Cr(VI) reduction
      rate including carbon source type, pH, initial Cr(VI) concentration and amount of
      cells inoculum were thoroughly studied. Malate was found to yield maximum
      biotransformation, followed by succinate and glucose, with the reduction rate of
      60.86%, 43.76% and 28.86% respectively. The optimum pH for Cr(VI) reduction was
      7.0, with reduction efficiency of 61.71% being achieved. With the increase of
      initial Cr(VI) concentration, the rate of Cr(VI) reduction decreased. The
      reduction was inhibited strongly when the initial Cr(VI) concentration increased
      to 157 mg/L. As the amount of cells inoculum increased, the rate of Cr(VI)
      reduction also increased. The mechanism of Cr(VI) reduction and final products
      were also analysed. The results suggested that the soluble enzymes appear to be
      responsible for Cr(VI) reduction by Pseudomonas aeruginosa, and the reduced
      Cr(III) was not precipitated in the form of Cr(OH)3.

PMID- 15559816
TI  - Removal of high concentrated ammonia nitrogen from landfill leachate by
      landfilled waste layer.
AB  - The landfill of municipal solid waste (MSW) could be regarded as denitrification
      reactor and involved in ammonia nitrogen biological removal process. In this
      research, the process was applied to municipal solid waste collected in Shanghai,
      China, which was characterized by high food waste content. The NH4(+) removal
      efficiency in the system of SBR nitrifying reactor followed by fresh and matured
      landfilled waste layer in series was studied. In the nitrifying reactor, above
      90% of NH4(+) in leachate was oxidized to NO2(-) and NO3(-). Then high
      concentrated NO2 and N3(-) were removed in the way of denitrification process in
      fresh landfilled waste layer. At the same time, degradation of fresh landfilled
      waste was accelerated. Up to the day 120, 136.5 gC/(kg dry waste) and 17.9 gN/(kg
      dry waste) were converted from waste layer. It accounted for 50.15% and 86.89% of
      the total carbon and nitrogen content of preliminary fresh waste, which was 4.42
      times and 5.17 times higher than that of reference column respectively. After
      filtering through matured landfilled waste, BOD5 concentration in leachate
      dropped to below 100 mg/L, which would not affect following nitrification
      adversely. Because the matured landfilled waste acted as a well methanogenic
      reactor, 23% of carbon produced accumulatively from fresh landfilled waste
      degradation was converted into CH4.

PMID- 15559817
TI  - Plasma induced degradation of Indigo Carmine by bipolar pulsed dielectric barrier
      discharge(DBD) in the water-air mixture.
AB  - Degradation of the Indigo Carmine (IC) by the bipolar pulsed DBD in water-air
      mixture was studied. Effects of various parameters such as gas flow rate,
      solution conductivity, pulse repetitive rate and ect., on color removal
      efficiency of dying wastewater were investigated. Concentrations of gas phase o3
      and aqueous phase H2O2 under various conditions were measured. Experimental
      results showed that air bubbling facilitates the breakdown of water and promotes
      generation of chemically active species. Color removal efficiency of IC solution
      can be greatly improved by the air aeration under various solution
      conductivities. Decolorization efficiency increases with the increase of the gas
      flow rate, and decreases with the increase of the initial solution conductivity.
      A higher pulse repetitive rate and a larger pulse capacitor C(p) are favorable
      for the decolorization process. Ozone and hydrogen peroxide formed decreases with
      the increase of initial solution conductivity. In addition, preliminary analysis
      of the decolorization mechanisms is given.

PMID- 15559818
TI  - Application of ion chromatography to the determination of water-soluble inorganic
      and organic ions in atmospheric aerosols.
AB  - A simple, sensitive and convenient ion chromatography(IC) method was established
      for the simultaneous determination of twelve water-soluble inorganic anions(F- ,
      Cl- , NO2(-), NO3(-), SO3(2-), SO4(2-) , PO4(3-)), and fifteen water-soluble
      organic ions(formate, acetate, MSA, oxalate, malonate, succinate, phthalates,
      etc.) in atmospheric aerosols. The linear concentrations ranged from 0.005
      microg/m3 to 500 microg/m3 ( r = 0.999-0.9999). The relative standard deviation
      (RSD) were 0.43%-2.00% and the detection limits were from 2.7 ng/m3 to 88 ng/m3.
      The proposed method was successfully applied to the simultaneous determination of
      those inorganic ions and organic ions in PM2.5 of Beijing.

PMID- 15559819
TI  - Optimization of solid fermentation of cellulase from Trichoderma koningii.
AB  - To exploit peashrub resources in Ordos as fodders, it is very crucial to realize
      industrial production of cheap cellulase of high activity by optimizing culture
      technology, especially culture substrate. In this study, a new prescription
      experiment based on uniform design ideal was invented and successfully applied in
      the solid fermentation of Trichoderma koningii F244, which was performed with two
      different temperature degrees. The activities of FPA, cotton lyase, CMCase and
      beta-glucosidase were assayed and then mathematical models of enzymatic
      activities, which were figured out by Unconstraint Mathematical Programming, were
      developed by Multivariate Regression Program of SPSS10.0. Enzymatic activities of
      optimized substrate prescriptions corresponding to mathematical models were
      forecasted to determine an ideal substrate prescription. It is revealed that in
      solid fermentation, Tween80 has negative effect on cellulase production.
      Furthermore, the ideal prescription for cellulase complex production by
      Trichoderma koningii F244 was straw powder 16.9%, wheat bran 26.5%, (NH4)2SO4
      9.5% and water 47.1%, whose corresponding cellulase activity was expected to be
      at the same high level with that of Trichoderma reesei Q9414 on its own
      recommended substrate. Especially, goats mainly fed on peashrub tissues mixed
      with cellulase complex of this prescription and culture technology, got an
      incremental ratio of 0.3 kg/d, which brought a very promising feeding prospect
      for local peashrub resource. By populization of this cellulase complex, it can
      integrate living standard, economic construction of local residents into
      vegetational restoration tightly and thus this paper will be very meaningful to
      be use for reference for western China like Ordos to realize its sustainable
      development of economy, society and environment.

PMID- 15559820
TI  - Low SO2 emission from CFB co-firing MSW and bituminous.
AB  - Influence of co-firing rate on SO2 emission from co-firing municipal solid waste
      (MSW) and bituminous containing high amount of sulfur (1.79%) was studied in a
      0.15 MWt circulating fluidized bed (CFB). The temperature selected is 1123 K,
      typical for MSW incineration using CFB. The particle concentration in the
      dilution zone of the furnace, the alkali metal concentration and sulfate
      concentration in the recirculating ash and fly ash, and flue gas composition were
      determined. The results showed that the addition of MSW leads to a significant
      decrease in SO2 emission. Concentration of SO2 in flue gas decreased to 0 with
      the co-firing rate greater than 51%. This reduction in SO2 emission is attributed
      both to the high particle concentration in the dilution zone of the furnace, the
      high content of alkali metals in the bed material, and to the comparatively high
      concentration of HCI in flue gas during co-firing of MSW and bituminous.

PMID- 15559821
TI  - Simultaneous determination of 4-tert-octylphenol, 4-nonylphenol and bisphenol A
      in Guanting Reservoir using gas chromatography-mass spectrometry with selected
      ion monitoring.
AB  - The wide occurrence of estrogenic compounds 4-tert-octylphenol, 4-nonylphenol,
      bisphenol A in surface water of Guanting Reservoir was successfully determined.
      The target compounds in water samples were preconcentrated by liquid-liquid
      extraction with dichloromethane, derivatized by trifluoroacetic anhydride, and
      quantified by gas chromatography-mass spectrometry(GC-MS) with selected ion
      monitoring (SIM). In the selected seven sampling sites (S1-S7), the concentration
      of NP in sample S7 was significantly higher than the other in reservoir. The
      status of pollution in S3 and S7 were much more serious. The concentrations of
      OP, NP and BPA were in the range of 44.5-48.8, 221.6-349.6 and 30.2-82.7 ng/L,
      respectively. The pollutants were mainly inputted from the upper river and
      released from sediments in Guanting Reservoir.

PMID- 15559822
TI  - Sensitized effect of beta-cyclodextrin on the fluorescence in the determination
      of carbaryl.
AB  - Based on the significant enhancement of fluorescence intensity of carbaryl in
      inclusion complex, a spetrofluorimetric method with high sensitivity was
      developed for the determination of carbaryl in aqueous solution. Under the
      optimum conditions, the complex had excitation and emission maxima at 278 nm and
      332 nm, respectively. The linear range of the method was 7.0 ng/ml-1500 ng/ml
      with a detection limit of 1.2 ng/ml. The proposed method was successfully used to
      determine quantitatively of carbaryl in cottonseeds.

PMID- 15559823
TI  - Validation of MODIS aerosol retrievals and evaluation of potential cloud
      contamination in East Asia.
AB  - MODIS aerosol retrievals onboard Terra/Aqua and ground truth data obtained from
      AERONET (Aerosol Robtic Network) solar direct radiance measurements are
      collocated to evaluate the quality of the former in East Asia. AERONET stations
      in East Asia are separated into two groups according to their locations and the
      preliminary validation results for each station. The validation results showed
      that the accuracy of MODIS aerosol retrievals in East Asia is a little worse than
      that obtained in other regions such as Eastern U.S., Western Europe, Brazil and
      so on. The primary reason is due to the improper aerosol model used in MODIS
      aerosol retrieval algorithm, so it is of significance to characterize aerosol
      properties properly according to long-term ground-based remote sensing or other
      relevant in situ observations in order to improve MODIS retrievals in East Asia.
      Cloud contamination is proved to be one of large errors, which is demonstrated by
      the significant relation between MODIS aerosol retrievals versus cloud fraction,
      as well as notable improvement of linear relation between satellite and ground
      aerosol data after potential cloud contamination screened. Hence, it is suggested
      that more stringent clear sky condition be set in use of MODIS aerosol data. It
      should be pointed out that the improvement might be offset by other error sources
      in some cases because of complex relation between different errors. Large
      seasonal variation of surface reflection and uncertainties associated with it
      result in large intercepts and random error in MODIS aerosol retrievals in
      northern inland of East Asia. It remains to be a big problem to retrieve aerosols
      accurately in inland characterized by relatively larger surface reflection than
      the requirement in MODIS aerosol retrieval algorithm.

PMID- 15559824
TI  - Community analysis of ammonia oxidizer in the oxygen-limited nitritation stage of
      OLAND system by DGGE of PCR amplified 16S rDNA fragments and FISH.
AB  - OLAND (oxygen limited autotrophic nitrification and denitrification) nitrogen
      removal system was constructed by coupling with oxygen limited nitritation stage
      and anaerobic ammonium oxidation stage. Ammonia oxidizer, as a kind of key
      bacteria in N cycle, plays an important role at the oxygen limited nitritation
      stage of OLAND nitrogen removal system. In this study, specific amplification of
      16S rDNA fragment of ammonia oxidizer by nested PCR, separation of mixed PCR
      samples by denaturing gradient gel electrophoresis (DGGE), and the quantification
      of ammonia oxidizer by fluorescence in situ hybridization (FISH) were combined to
      investigate the shifts of community composition and quantity of ammonia oxidizer
      of the oxygen limited nitritation stage in OLAND system. It showed that the
      community composition of ammonia oxidizer changed drastically when dissolved
      oxygen was decreased gradually, and the dominant ammonia oxidizer of the steady
      nitrite accumulation stage were completely different from that of the early stage
      of oxygen limited nitritation identified by DGGE. It was concluded that the
      Nitrosomonas may be the dominant genus of ammonia oxidizer at the oxygen limited
      nitritation stage of OLAND system characterized by nested PCR-DGGE and FISH, and
      the percentage of Nitrosomonas was 72.5% +/- 0.8% of ammonia oxidizer at the
      steady nitrite accumulation stage detected by FISH.

PMID- 15559825
TI  - Effects of bifenthrin on Daphnia magna during chronic toxicity test and the
      recovery test.
AB  - The acute and chronic toxic effects of bifenthrin on Daphnia magna were studied.
      The results showed that 24 h-EC50, 48 h-LC50 and 96 h-LC50 of bifenthrin on D.
      magna were 3.24, 12.40 and 1.40 microg/L respectively. And the LOEC and NOEC of
      bifenthrin were 0.02 and 0.004 microg/L respectively. The recovery test of
      bifenthrin on Daphnia magna was presented. Daphnia magna (F0 generation) were
      exposed during 21 d to different bifenthrin concentrations. Offspring (animals
      from the first and third brood: F1 (1st) and F1 (3rd), respectively) were
      transferred to a free pesticide medium during a 21 d recovery period. In this
      recovery study, survival, growth, reproduction (mean total young per female,
      onset of reproduction and number broods per female) and the intrinsic rate of
      natural increase (r) were assessed as parameters. Reproduction such as number of
      young per female as well as length was still reduced in F1 (1st) generation
      daphnids from parentals (F0) exposed to the bifenthrin. However F, (3rd)
      individuals from parentals exposed to pesticide concentrations were able to
      restore reproduction when a recovery period of 21 d was allowed, but the length
      of F, (3rd) from parentals exposed to the 0.5 and 0.75 microg/L bifenthrin
      concentration was still significantly effected (P < 0.05).

PMID- 15559826
TI  - Decomposition dynamic of higher plant pigments by HPLC analysis.
AB  - The fate of the litter of dominant vegetation(willows and reeds) is one of the
      aspects studied in the frame of the project "Onderzoek Milieu Effecten
      Sigmaplan". One of the questions to be considered is how long the litter stays
      within the estuary. In this paper, the time the leaf litter (Salix triandra and
      Phragmites australis) stayed in the Schelde estuary was studied by using plant
      pigment as biomarkers with HPLC application. After analyzing the original data
      from the incubation experiment described by Dubuison and Geers (1999), the
      decomposition dynamics patterns of pigments were analyzed and described, and
      these decomposition dynamics patterns were used as calibration patterns. By using
      Spearman Rank Order Correlation, the calibration patterns of the pigments which
      were significant (p < 0.05) were grouped. In this way, several groups of the
      calibration patterns of pigment decomposition were achieved. The presence or
      absence of these groups of pigments (whether they can be detected or not from
      HPLC) was shown to be useful in determining the time the litter has stayed in the
      water. Combining data of DW and POC, more precise timing can be obtained.

PMID- 15559827
TI  - Electrochemical oxidation of polyethylene glycol in electroplating solution using
      paraffin composite copper hexacyanoferrate modified (PCCHM) anode.
AB  - Electrochemical oxidation of polyethylene glycol (PEG) in an acidic (pH 0.18 to
      0.42) and high ionic strength electroplating solution was investigated. The
      electroplating solution is a major source of wastewater in the printing wiring
      board industry. A paraffin composite copper hexacyanoferrate modified (PCCHM)
      electrode was used as the anode and a bare graphite electrode was used as the
      cathode. The changes in PEG and total organic carbon (TOC) concentrations during
      the course of the reaction were monitored. The efficiency of the PCCHM anode was
      compared with bare graphite anode and it was found that the former showed
      significant electrocatalytic property for PEG and TOC removal. Chlorides present
      in the solution were found to contribute significantly in the overall organic
      removal process. Short chain organic compounds like acetic acid, oxalic acid,
      formic acid and ethylene glycol formed during electrolysis were identified by
      HPLC method. Anode surface area and applied current density were found to
      influence the electro-oxidation process, in which the former was found to be
      dominating. Investigations of the kinetics for the present electrochemical
      reaction suggested that the two stage first-order kinetic model provides a much
      better representation of the overall mechanism of the process if compared to the
      generalized kinetic model.

PMID- 15559828
TI  - Isolation and characterization of deodorizing bacteria for organic sulfide
      malodor.
AB  - Strain JII screened out from different odor origins can efficiently degrade
      methyl mercaptan and ethanethiol whereas has no ability to remove dimethyl
      sulfide. The results indicated that the strain JII breaks only the C-SH bond. The
      optimum temperature and pH of JII are 20-30 degrees C and 6.0-8.3 respectively. A
      systematic identification method-16S rDNA gene sequence comparison, for
      deodorizing bacteria was carried out. The 16S rDNA gene sequence analysis of
      strain JII showed the highest level of 97% homology to Rape rhizosphere.

PMID- 15559829
TI  - Chemical composition and quantitative relationship between meteorological
      condition and fine particles in Beijing.
AB  - The recent year's monitor results of Beijing indicated that the pollution level
      of fine particles PM2.5 showed an increasing trend. To understand pollution
      characteristics of PM2.5 and its relationship with the meteorological conditions
      in Beijing, a one-year monitoring of PM2.5 mass concentration and correspondent
      meteorological parameters was performed in Beijing in 2001. The PM2.5 levels in
      Beijing were very high, the annual average PM2.5 concentration in 2001 was 7
      times of the National Ambient Air Quality Standards proposed by US EPA. The major
      chemical compositions were organics, sulfate, crustals and nitrate. It was found
      that the mass concentrations of PM2.5 were influenced by meteorological
      conditions. The correlation between the mass concentrations of PM2.5 and the
      relative humidity was found. And the correlation became closer at higher relative
      humidity. And the mass concentrations of PM2.5 were negtive-correlated to wind
      speeds, but the correlation between the mass concentration of PM2.5 and wind
      speed was not good at stronger wind.

PMID- 15559830
TI  - Estimation of runoff and sediment yield in the Redrock Creek watershed using
      AnnAGNPS and GIS.
AB  - Sediment has been identified as a significant threat to water quality and channel
      clogging that in turn may lead to river flooding. With the increasing awareness
      of the impairment from sediment to water bodies in a watershed, identifying the
      locations of the major sediment sources and reducing the sediment through
      management practices will be important for an effective watershed management. The
      annualized agricultural non-point source pollution(AnnAGNPS) model and newly
      developed GIS interface for it were applied in a small agricultural watershed,
      Redrock Creek watershed, Kansas, in this pilot study for exploring the
      effectiveness of using this model as a management tool. The calibrated model
      appropriately simulated monthly runoff and sediment yield through the practices
      in this study and potentially suggested the ways of sediment reduction through
      evaluating the changes of land use and field operation in the model for the
      purpose of watershed management.

PMID- 15559831
TI  - Potential of weed species applied to remediation of soils contaminated with heavy
      metals.
AB  - To screen out a series of ideal plants that can effectively remedy contaminated
      soils by heavy metals is the main groundwork of phytoremediation engineering and
      the first step of its commercial application on a large scale. In this study,
      accumulation and endurance of 45 weed species in 16 families from an agricultural
      site were in situ examined by using the pot-culture field experiment, and the
      remediation potential of some weed species with high accumulation of heavy metals
      was assayed. The results showed that Solanum nigrum and Conyza canadensis can not
      only accumulate high concentration of Cd, but also strongly endure to single Cd
      and Cd-Pb-Cu-Zn combined pollution. Thus 2 weed species can be regarded as good
      hyperaccumulators for the remediation of Cd-contaminated soils. Although there
      were high Cd-accumulation in Artemigia selengensis, Znula britannica and
      Cephalanoplos setosum, their biomass was adversely affected due to action of
      heavy metals in the soils. If the problem of low endurance to heavy metals can be
      solved by a reinforcer, 3 weed species can be perhaps applied commercially.

PMID- 15559832
TI  - Comparison between controlled landfill reactor and conditioned landfill
      bioreactor.
AB  - Bioreactor landfills allow a more active landfill management that recognizes the
      biological, chemical and physical processes involved in a landfill environment.
      The laboratory-scale simulators of landfill reactors treating municipal solid
      wastes were studied, the effect of solid waste size, leachate recirculation,
      nutrient balance, pH value, moisture content and temperature on the rate of
      municipal solid waste (MSW) biodegradation were determined, and it indicated the
      optimum pH value, moisture content and temperature decomposing MSW. The results
      of waste biodegradation were compared with that of the leachate-recirculated
      landfill simulator and conservative sanitary landfill simulator. In the control
      experiment the antitheses of a decreasing trend of the organic load, measured as
      biological oxygen demand and chemical oxygen demand, was shown. An obvious
      enhancement of effective disposal from conservative sanitary landfill (CSL)
      simulator, to the leachate-recirculated landfill (LRL) simulator and to the
      conditioned bioreactor landfill (CBL) simulator would be noted, through
      displaying the compared results of solid waste settlement, heavy metal
      concentration in leachate, methane production rate, biogas composition, BOD and
      COD as well as their ratio.

PMID- 15559833
TI  - Getting the SNOMED ball rolling in Australia.

PMID- 15559834
TI  - New scrutiny on improper payments. Federal government heightens focus on
      estimating error.

PMID- 15559835
TI  - Achieving data quality. How data from a pediatric health information system earns
      the trust of its users.

PMID- 15559836
TI  - Getting better data from the MDS. Improving diagnostic data reporting in long
      term care facilities.

PMID- 15559837
TI  - What does your transcription format cost? Weighing the costs and benefits of
      different transcription formats.

PMID- 15559838
TI  - The research track. Career progressions in research for HIM professionals.

PMID- 15559839
TI  - Uncovering the relationship between IRBs and the HIPAA privacy rule.

PMID- 15559840
TI  - Delving into computer-assisted coding.

PMID- 15559841
TI  - Next steps for the EHR draft standard.

PMID- 15559842
TI  - What is security auditing?

PMID- 15559843
TI  - Reconciling the privacy rule and substance abuse record confidentiality.

PMID- 15559844
TI  - ICD-10: all in the family.

PMID- 15559845
TI  - One little lesion--so many choices. Part 1 of 2: the CPT aspect.

PMID- 15559846
TI  - 2005 ICD-9-CM codes and DRG changes.

PMID- 15559847
TI  - Driving decisions with data. In an EHR implementation, ensuring data integrity is
      high on the to-do list.

PMID- 15559848
TI  - Implantable polymeric artificial pancreas.

PMID- 15559849
TI  - Changes in morphology of starch-based prothestic thermoplastic material during
      enzymatic degradation.
AB  - This work evaluates the structural changes of an interpenetrated starch
      thermoplastic blend withstanding different enzymatic alpha-amylase degradation
      periods (up to 200 days), and establishes the relationships between the kinetics
      degradation rate and the structure of the material. It characterises the
      different stages of the enzymatic degradation process on starch/ethylenevinyl
      alcohol blends, based on the attack of the connected starch domains that can be
      accessed by the enzymatic solution. The completely encapsulated starch particles
      remain practically unchanged. Furthermore, it was also found that the enzymatic
      degradation process was limited after 100 days of immersion. In order to
      understand such phenomenon several techniques were used, namely differential
      scanning calorimetry, contact-angle measurements, high-performance liquid
      chromatography, Fourier transform infrared spectrometry, scanning electron
      microscopy and atomic force microscopy. The materials were evaluated with respect
      to the enzymatic degradation rate, surface morphology and degradation behaviour.
      The results show that the ethylene-vinylalcohol phase wraps the starch domains,
      preventing the respective degradation. Consequently, the degraded material in the
      solution comes only from the starch particles that could be reached by the
      enzyme.

PMID- 15559850
TI  - Differential degradation rates in vivo and in vitro of biocompatible poly(lactic
      acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery
      microchip.
AB  - The biocompatibility and biodegradation rate of component materials are critical
      when designing a drug-delivery device. The degradation products and rate of
      degradation may play important roles in determining the local cellular response
      to the implanted material. In this study, we investigated the biocompatibility
      and relative biodegradation rates of PLA, PGA and two poly(lactic-co-glycolic
      acid) (PLGA) polymers of 50:50 mol ratio, thin-film component materials of a drug
      delivery microchip developed in our laboratory. The in vivo biocompatibility and
      both in vivo and in vitro degradation of these materials were characterized using
      several techniques. Total leukocyte concentration measurements showed normal
      acute and chronic inflammatory responses to the PGA and low-molecular-weight PLGA
      that resolved by 21 days, while the normal inflammatory responses to the PLA and
      high-molecular-weight PLGA were resolved but at slower rates up to 21 days. These
      results were paralleled by thickness measurements of fibrous capsules surrounding
      the implants, which showed greater maturation of the capsules for the more
      rapidly degrading materials after 21 days, but less mature capsules of sustained
      thicknesses for the PLA and high-molecular-weight PLGA up to 49 days. Gel
      permeation chromatography of residual polymer samples confirmed classification of
      the materials as rapidly or slowly degrading. These materials showed thinner
      fibrous capsules than have been reported for other materials by our laboratory
      and have suitable biocompatibility and biodegradation rates for an implantable
      drug-delivery device.

PMID- 15559851
TI  - Growth inhibition of MCF-7 tumor cell line by phenylacetate linked to
      functionalized dextran.
AB  - We investigated the antiproliferative effect of phenylacetate covalently linked
      to dextran derivatives (DMCBPA conjugates) on human breast cancer MCF-7 cells. We
      show that free sodium phenylacetate (NaPA) inhibits the cell growth (IC50 = 14
      mM), while an important inhibitory effect is observed for DMCBPA conjugates. The
      IC50 dose of these conjugates is as low as 1.0 mg/ml, corresponding to 1.3 mM of
      phenylacetate. The precursors, dextran substituted with methylcarboxylate and
      benzylamide groups, did not affect the growth of MCF-7 tumor cells. We have
      observed that MCF-7 cell growth inhibition depends on amount of phenylacetate
      linked to the conjugate. The data indicated that an optimum antiproliferative
      effect is more significant when the amount of phenylacetate groups present on the
      dextran backbone is high. Analysis of doubling time by growth kinetics study
      shows that conjugates have more time-sustained effect than free NaPA. It is
      noteworthy that the inhibitory effect is observed at non-toxic concentration.
      Theses conjugates could be considered as acceptable derivatives to prevent tumor
      progression.

PMID- 15559852
TI  - Effect of thickness and PEG addition on the hydrolytic degradation of PLLA.
AB  - We previously demonstrated that cylindrical, biodegradable reservoirs fabricated
      with polylactide-polyethylene glycol (PLLA:PEG) films maintain constant
      permeability and enable zero-order drug delivery for up to 6 weeks in vitro. This
      research proposes that PEG not only enhances permeability but also extends of
      life of the device by allowing the escape of soluble degraded monomers thereby
      minimizing autocatalysis of PLLA. To test this hypothesis, cylindrical PLLA films
      with varying PEG concentrations (0-30%, w/w) and film-thickness (0.05-0.18 mm)
      were fabricated, and their degradation rate and thermal properties monitored for
      23 weeks in vitro. The decrease in PLLA molecular weight for all films followed
      bi-exponential kinetics that fit the equation: y(t) = M(e(-K1t) + e(-K2t)), as
      was determined by a Pearson's coefficient > 0.95 for all films. The constant M
      was empirically determined to be equal to have the initial molecular weight of
      the degrading polymer. The value of K1 was 5-60 orders of magnitude greater than
      K2 and was attributed to the autocatalytic degradation based on its dependence on
      PEG concentration, film thickness, and correlation with the enthalpy change
      associated with the glass transition (deltaCp). K2 was attributed to simple
      hydrolytic cleavage of PLLA. The decrease in the value of K1 with PEG
      concentration and thickness, and the correlation of K1 with deltaCp, confirmed
      that the PLLA degradation can be controlled by incorporating PEG, as well as by
      modifying thickness.

PMID- 15559853
TI  - Incorporation of polymer microspheres within fibrin scaffolds for the controlled
      delivery of FGF-1.
AB  - The purpose of this work was to examine the feasibility of a hybrid scaffold in
      which fibroblast growth factor-1 (FGF-1)-encapsulated microspheres are embedded
      within a fibrin gel. Such a tissue-engineered scaffold could be incorporated into
      surgical procedures to promote healing while simultaneously delivering
      therapeutic agents that promote angiogenesis. Fibrin has been extensively studied
      as an adhesive in plastic and reconstructive surgery and the enhancement of wound
      healing with embedded growth factors is desirable. We report the release of a
      fluorescently-labeled model protein, bovine serum albumin (BSA-FITC), from
      poly(D,L-lactic-co-glycolic acid) microspheres embedded in the fibrin scaffold.
      The protein release was found to be significantly delayed as compared to
      microspheres alone during the initial 24 h of release. Additionally, FGF-1 was
      examined for efficient incorporation into these scaffolds as a potential mitogen
      for fibroblasts. The optimal concentration of FGF-1 in the media that enhanced
      NIH-3T3 fibroblast proliferation over 48 h was determined to be 0.1 microg/ml.
      The release of FGF-1 from microspheres embedded in fibrin gels was compared to
      FGF-1-encapsulated microspheres alone. The release of FGF-1 from the
      microsphere/scaffolds was delayed as compared to the release of FGF-1 from
      microspheres alone. This novel hybrid fibrin/microsphere scaffold is a feasible
      delivery system for growth factors.

PMID- 15559854
TI  - Pay for Part B drugs cut, but docs can bill for more services.

PMID- 15559855
TI  - Perspectives. Five years after medical-error report, progress is hard to see.

PMID- 15559856
TI  - Damages caps win, lose in states.

PMID- 15559857
TI  - Athenian echoes.

PMID- 15559858
TI  - Dendritic cells: from the fabric of immunology.

PMID- 15559859
TI  - Ir genes--forty years on.

PMID- 15559860
TI  - FACS innovation: a view from Stanford.

PMID- 15559861
TI  - Bloodstream infection complicating trauma.
AB  - BACKGROUND: Bloodstream infection (BSI) is recognized as an important infectious
      complication of major trauma. However, its occurrence, the risk factors
      contributing to its development, and its outcomes have not been well described.
      DESIGN: Cohort with linkage of regional trauma and microbiology databases.
      PATIENTS: Adult trauma patients with injury severity score (ISS) > or = 12
      admitted to a regional trauma centre during a 33-month period. RESULTS: Of 1797
      victims of acute trauma identified (median ISS 20; interquartile range [IQR] 16
      25), 71 (4%) had 77 episodes of BSI, for an overall rate of 2.9 per 1000 hospital
      days. BSI in the majority of patients (37 of 72, or 52%) had onsets within the
      first week of hospitalization; 7 (10%) patients had community-acquired BSI (onset
      within 2 d). Independently associated with the development of nosocomial BSI were
      higher ISSs (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07);
      requirement for ICU admission (OR 7.06, CI 3.38-14.75); and burns (OR 5.75, CI
      2.16-15.30). Although trauma-related BSI was a predictor of increased in-hospital
      case fatality (15/71 v. 208/1726; relative risk 1.75, CI 1.10-2.78), it was not
      an independent predictor of death. CONCLUSION: In our series, 1 in 25 major
      trauma cases was complicated by BSI. The infection occurred within the first week
      after injury in over half of our cases. Knowledge of the epidemiology of these
      infections will be important for planning preventive or early therapeutic
      efforts.

PMID- 15559862
TI  - Hepatitis A seroprevalence and risk factors among day-care educators.
AB  - BACKGROUND: Day-care centres play a role in the epidemiology of hepatitis A virus
      (HAV). Up-to-date documentation on its seroprevalence and potential risk factors
      among day-care educators, who may be at risk for significant HAV morbidity, is
      nevertheless lacking. The availability of a hepatitis A vaccine provides an
      additional opportunity for prevention in this population. To determine the
      seroprevalence of previous HAV infection among day-care educators and to identify
      potential risk factors, we undertook a survey. METHODS: Of 167 randomly selected
      centres, 81 centres participated. Directors and educators completed
      questionnaires on risk factors. Sera were collected during on-site visits from
      October through December 2001. RESULTS: Seroprevalence of previous HAV infection
      in 492 participating educators was 35.6%. Significant risk factors in
      multivariate analysis included birth in a high-versus moderate/low-income country
      (odds ratio [OR] 20.8; 95% confidence interval [CI] 9.4-46.0); self-reported HAV
      vaccination (OR 6.1, CI 2.9-13.0); travel to endemic areas (OR 2.4, CI 1.3-4.2);
      and age (5-yr OR 1.5, CI 1.3-1.7). When Canadian-born educators were analyzed
      separately, an association was found between seropositivity and the number of
      years worked in daycare centres (5-yr OR 1.3, CI 1.0-1.8). INTERPRETATION: This
      represents the first study in Canada designed to examine risk factors for
      previous HAV infection among adult day-care educators. As a group, their risk
      factors for seropositivity are similar to those in the general population.
      However, educators born in Canada (a low-endemicity area for hepatitis A) appear
      to be at additional risk by working in day-care centres. The benefits of HAV
      screening and routine vaccination of day-care educators need to be examined.

PMID- 15559863
TI  - Cardiovascular adaptation to chronic anemia in the elderly: an echocardiographic
      study.
AB  - OBJECTIVE: To study the effects of chronic severe anemia on the aging heart.
      METHODS: We studied 41 elderly patients (mean age 69.8 yr, standard deviation
      [SD] 3.9 yr) suffering from chronic severe anemia (mean hemoglobin 6.3, SD 0.5
      g/dL) with no history of cardiac disease, along with 63 healthy age- and sex
      matched controls. Assessment included physical examination, electrocardiogram and
      Doppler echocardiography. RESULTS: Although heart rates were similar between
      patients and controls, arterial blood pressures were significantly lower in
      patients (mean pressure 92.7 mm Hg, SD 7.9, v. mean 102.1 mm Hg, SD 3.5; p <
      0.001). No patient was found to have congestive heart failure. Patients with
      chronic anemia had larger diameters of the left (end-systolic 35.28, SD 4.20, v.
      33.73, SD 2.08 mm, p < 0.05; end-diastolic 53.33, SD 4.55, v. 50.37, SD 2.10 mm,
      p < 0.001) and right ventricles (30.76, SD 3.98, v. 29.04, SD 2.04 mm; p < 0.05),
      and greater left-ventricular mass (277.64, SD 62.85, v. 212.91, SD 24.87 g; p <
      0.001). Fractional shortening did not differ significantly (0.33, SD 0.04, v.
      0.33, SD 0.03). The load-independent end-systolic index was lower in patients
      (2.67, SD 0.56, v. 3.87, SD 0.49 kdyn x m2/cm5; p < 0.001) along with end
      systolic stress and total systemic resistance (p < 0.001) than controls, whereas
      the cardiac index was higher (4.31, SD 1.29, v. 2.73, SD 0.51 L/min/m2; p <
      0.001). Differences between the 2 groups in diastolic function indices and
      pulmonary arterial pressures were not statistically significant. INTERPRETATION:
      Chronic severe anemia is well tolerated by the aging heart. Neither congestive
      heart failure nor clearly evident left-ventricular dysfunction were encountered.
      The heart exhibited an adaptive potential through remodelling by means of the
      Frank-Starling mechanism and afterload reduction. However, the lower end-systolic
      index in patients suggests that ventricular performance was marginally
      compromised. This state of high output was achieved mainly by increased stroke
      volume, with little contribution from heart rate.

PMID- 15559865
TI  - Signals find their target: drug design and diagnosis based on intracellular
      signalling.

PMID- 15559864
TI  - Probiotics in surgical wound infections: current status.
AB  - BACKGROUND: Probiotics--live microorganisms that confer a health benefit when
      taken in adequate amounts, usually as food supplements--are receiving renewed
      attention in the medical community. Some have been found to play a role in
      disease remediation. However, mainstream medicine and science remain divided
      about the validity of health claims made about them. METHODS: To clarify the
      potential value of probiotics, we reviewed the scientific data on their role in
      preventing and treating surgical infections as well as some of our own studies of
      the effects of certain strains of lactobacilli on surgical implant infections.
      PRINCIPAL FINDINGS: There is little rigorous evidence that probiotics may be
      beneficial in the prevention and treatment of wound infections. However, data
      from 3 clinical trials and from our laboratory indicate that certain strains of
      probiotic lactobacilli and their byproducts may help reduce infection rates in
      surgical patients and may ameliorate staphylococcus-related infections of
      surgical implants. CONCLUSION: Although there is good clinical evidence that
      certain probiotics may be beneficial in conditions such as diarrheal and
      inflammatory bowel diseases, more studies are required to apply these concepts to
      the prevention and treatment of wound and other surgical infections.

PMID- 15559866
TI  - Shrink that suitcase!

PMID- 15559867
TI  - [Speech held by the Secretary of Public Health, Dr Julio Frenk Mora, during the
      celebrations of the 60th Anniversary of the National Institute of Cardiology
      Ignacio Chavez at the facilities of the Institute].

PMID- 15559868
TI  - [The emblem of the National Institute of Cardiology "Ignacio Chavez"].

PMID- 15559869
TI  - [Diminished vascular density in the aortic wall. Morphological and functional
      characteristics of atherosclerosis].
AB  - PURPOSE: To determine disproportion in thicknesses of the vascular wall and vasa
      vasorum in eight fragments of human aorta because of the irregular distribution
      of atherosclerosis in arterial walls. METHOD: The length and thickness of the
      wall and its layers were measured and the vasa vasorum were conted. Vascular
      density, considered as the number of vessels per square millimeter in healthy and
      diseased areas, was calculated along with mean value, variance, standard
      deviation and the confidence interval for values and null hypotesis. Variances
      were analyzed, and the comparative and paired "t" test was applied. RESULTS:
      There were differences in thicknesses of the healthy (27 :m) and diseased (120.5
      :m) intima (p < 0.001) and between the healthy (125.2 :m) and diseased (102.3 :m)
      media (P < 0.001). Vascular density was higher in healthy fragments (mean +/- Cl
      99% = 4.40 +/- 1.4 vs 2.20 +/- 0.8, = < 0.001 for Ha; 0 +/- 1.0775 for Ho; paired
      "t" 2.1 +/- 1.1, P < 0.01), and higher compared to the healthy intima area (31.6
      vs 5.1, P < 0.01). There were no differences compared to the media layer area.
      The relation between the number of vessels and the length of the vascular
      segments was greater in the healthy fragments (mean +/- Cl 95% = 4.9 +/- 1.02 vs
      3.5 +/- 0.68; 1.4 difference, P < 0.05). CONCLUSION: Vascular density is lower in
      the atherosclerotic aortic wall than in the healthy aorta and this could initiate
      the pathologic process.

PMID- 15559870
TI  - [Secondary Raynaud's syndrome: skin blood flow decrease between the ischemic
      episodes and prolongation of the vasoconstriction during the respiratory
      maneuvers].
AB  - The Raynaud's syndrome is an episodic skin ischemia manifested by pallor,
      cyanosis and erythema of the fingers in response to cold or emotional stress. The
      exact pathophysiology is unknown but it has been hypothetised that may be due to
      an autonomic alteration in the sympathetic innervation of skin blood vessels.
      OBJECTIVE: To study the changes of heart rate and skin blood flow (SBF) in
      healthy subjects and in patients with secondary Raynaud's syndrome during
      different respiratory maneuvers: 1. spontaneous respiration; 2. rhythmic
      respirations (RR), 3. sudden inspirations (SI), and 4. Valsalva maneuver (VM).
      METHODS: We studied 22 healthy subjects and 22 patients with secondary Raynaud's
      syndrome. The variables measured were: 1) RR intervals; 2) amplitudes of SBF; 3)
      percentage of decrease of SBF; 4) latency of the maximum decrease of SBF.
      RESULTS: In all patients with secondary Raynaud's syndrome the SBF was decreased
      basally during spontaneous rations and during all respiratory maneuvers (p <
      0.001). The mean latency of recovery of the SBF was prolonged during sudden deep
      inspiration. The patients with Raynaud also had significant basal tachycardia at
      rest (p < 0.003). CONCLUSIONS: The basal skin blood flow during spontaneous
      respirations and in asymptomatic periods is decreased in patients with Raynaud's
      syndrome; this may be related to endothelial arterioral damage. The SBF was also
      significantly decreased dynamically during sudden inspirations (SI), rhythmic
      breathing (RR) and Valsalva maneuver (VM). This dynamic change suggests
      sympathetic hyperactivity.

PMID- 15559871
TI  - [Losartan versus enalapril in the reduction of left ventricular hypertrophy
      secondary to systemic arterial hypertension].
AB  - OBJECTIVE: To compare losartan and enalapril on reduction of left ventricular
      hypertrophy. MATERIAL AND METHODS: Longitudinal, prospective, comparative,
      controlled study, of patients with moderate systemic arterial hypertension and
      echocardiographically proven left ventricular hypertrophy, randomized for
      treatment during six months with losartan 100 mg daily or enalapril 20 mg daily.
      The reduction of left ventricular mass index, was evaluated by echocardiogram
      basal and to six months. STATISTICAL ANALYSIS: Student's t, Spearman and Pearson
      correlation coefficients. RESULTS: 85 patients finished the study (43 in the
      losartan group and 42 in the enalapril group). After six months of treatment, the
      blood pressure values and the left ventricular mass index decreased in losartan
      and enalapril (p = .0000001 y .00001 respectively), without significative
      difference in the intergrupal comparative. We found correlation between diastolic
      and media blood pressure reduction (but not for systolic) and the decrease in
      left ventricular mass index in both groups. CONCLUSIONS: Both drugs were equally
      effective for control systemic arterial hypertension and produced a significant
      reduction of left ventricular hypertrophy, with modification of geometrical
      pattern to short time.

PMID- 15559872
TI  - [Usefulness of simple scheme for the diagnosis of cardiac arrhythmias].
AB  - OBJECTIVE: To determine whether an algorythm designed at our Electrophysiology
      Unit could facilitate the electrocardiographic diagnosis of tachyarrhythmias.
      METHODS: Twenty two first-year cardiology residents, general practitioners and
      last-year medical students attended an electrophysiology course. One hundred ECG
      of tachyarrhythmic patients were distributed to the participants who were then
      randomly divided into 2 groups. Group A analyzed the ECG with the help of the
      algorythm, whereas Group B analyzed them without it. Results were compared to
      those obtained by an electrophysiologist. RESULTS: Group A diagnosis coincided
      with that of the electrophysiologist in 41% of the cases. In Group B the
      concordance reached 64% (p = 0.0000013). There was no between-group difference
      regarding the type and number of uninterpreted ECG. CONCLUSIONS: The decision
      tree increases diagnostic accuracy in less expert hands. This could in turn
      entail an improvement in the therapeutic measures applied to the study of
      arrhythmias.

PMID- 15559873
TI  - [Tako-Tsubo syndrome (transient antero-apical dyskinesia): first case reported in
      Latin America and review of the literature].
AB  - Tako-Tsubo syndrome (TTS) is a recently described entity that can mimic an acute
      myocardial infarction. It is characterized by anginal chest pain with ST-T
      elevation in precordial leads, no coronary obstruction on angiography, and as its
      distinctive feature, a reversible left ventricular antero-apical ballooning with
      basal hyperkinesis. TTS is more frequent in female and elderly patients and in an
      article published in 2001 it was mentioned that only two cases had been reported
      outside Japan. We describe a typical case of recurrent TTS triggered by intense
      emotional stress. This is the first case reported from Latin America. A review of
      the literature suggests that TTS is more frequent than previously thought but
      apparently due to lack of awareness of this entity it can go unrecognized.
      Identification of TTS is of clinical importance because its management and
      prognosis differs significantly from that of an acute myocardial infarction that
      results from the thrombotic occlusion of a coronary atherosclerotic plaque.

PMID- 15559874
TI  - [On metabolic therapeutics G-I-K in surgery of cardiac patients].
AB  - The basic principles of the metabolic therapeutics with glucose-insulin-potassium
      solutions, already proposed by Dr. Demetrio Sodi Pallares, are exposed.
      Chronologic succession of this treatment during the preoperative, transoperative
      and postoperative phases of heart surgery, as well as some personal observations
      of one of the authors, are described. The glucose-insulin-potassium solution is a
      powerful system, providing very useful energy to protect the injured myocardium
      during cardiovascular surgery. Many publications support this assertion. The most
      recent ones indicate a reduction of low output syndromes due to interventions on
      coronary arteries, as well as a significant diminution of circulating fatty acids
      after primary angioplasty. The mentioned solution, in higher concentrations than
      the initial one, could become routine therapeutics in medicine and surgery
      centers, in general.

PMID- 15559875
TI  - [Positron emission tomography (PET): a useful tool for the assessment of cardiac
      metabolism].
AB  - Under normal conditions, myocardial metabolism is based on the oxidation of fatty
      acids and in a lesser extent carbohydrates. Cardiac function depends upon an
      adequate supplement of adenosine triphosphate (ATP) by these substrates. However,
      the main source of energy is susceptible to change upon a various physiologic
      (exercise) as well as pathologic (ischemia-reperfusion) conditions. Recently,
      carnitine has gained attention as a modulator of fatty acids and carbohydrates
      metabolism by means of modifying intramitochondrial Acetyl-CoA/CoA ratio.
      Disturbances in fatty acids and carbohydrates metabolism in the myocardium have
      been associated with cardiovascular diseases (chronic ischemic disease,
      ventricular hypertrophy and dilated cardiomyopathy). The evaluation of cardiac
      metabolism attains great value regarding diagnosis, treatment and prognosis of
      these diseases. Currently, positron emission tomography (PET) is one of the
      preferred methods to evaluate cardiac energy metabolism in clinical practice. In
      PET images the tracers most commonly used are 11C-palmitate, 11C-acetate y
      18Fluoro-2-deoxyglucose (FDG), the first two are employed to assess fatty acids
      oxidation and FDG is used to evaluate carbohydrates metabolism.

PMID- 15559876
TI  - [Posterobasal aneurysm of left ventricle].

PMID- 15559877
TI  - [Hypercholesterolemia and hypertension in Mexico: urban conjunctive consolidation
      with obesity, diabetes and smoking].
AB  - AIMS: To know the prevalence and the interaction among the principal
      cardiovascular risk factors such as hypercholesterolemia (HCL), hypertension
      (HTA), overweight, carbohydrates metabolism disturbances, and smoking, an urban
      survey was performed in the six Mexican Republic states, where the national
      population is more concentrated. METHODS: This survey was transversally designed
      using the WHO type-III model in 120,005 adults from 6 highly populated urban
      centers (Mexico City, Guadalajara, Leon, Puebla, Monterrey andTijuana) were
      included. A blood sample from each person was obtained to quantify fasting
      glucose and cholesterol. Blood pressure, height and weight were measured using
      daily validated systems. Data were analyzed by a multicategorical conjunctive
      consolidation model and by multiple regression models. RESULTS: HCL global
      prevalence showed to be 43.3% for a population with an average age of 44.1 years.
      Female gender showed a slightly but statistically significant greater prevalence
      of HCL than male gender (44% vs 42.2%). From whole women population 33.2%
      declared to be in menopause, and 59.7% of them had HCL. In addition, HCL was
      directly related to body mass index (BMI). Thus, in those subjects with BMI < 25
      showed a HCL prevalence 34.1%; while those with BMI was between 25 and 29.9, the
      HCL prevalence was 45.9%, and in those subjects with BMI > or = 30 Kg/m2, ranked
      a HCL prevalence of 47.3%. The prevalence of hypertension was 30.2% and 52.5% of
      them had HCL prevalence. Type-2 diabetes mellitus prevalence (DM-2) was 10.7%,
      55.2% of them had HCL. In the group aged between 20 to 34 years old, the obesity
      was the principal determinant for higher HCL prevalence. The HCL prevalence
      showed to be quite similar in population with and without smoking. In conclusion,
      HCL prevalence shows 4 progressively increasing gradients associated with age,
      HTA, DM-2 and BMI.

PMID- 15559878
TI  - [Right coronary artery fistula draining into the right ventricle].

PMID- 15559879
TI  - [Clinical and laboratory problems related to the application of antibiotics].

PMID- 15559880
TI  - [Successful application of evidence-based medicine and clinical epidemiology in
      clinical medicine].

PMID- 15559881
TI  - Tackling surgical infection prevention takes teamwork.
AB  - Even though infection control practices have improved dramatically in the United
      States, surgical infections still are a problem for many hospitals, ranking as
      the second most common cause of nosocomial infections. But hospitals are finding
      ways to fight back by implementing best practices, redesigning systems, and using
      hospital-wide teams--which include administrators, surgeons, nurses,
      anesthesiologists, pharmacists, and environmental services staff--that cut across
      many departments.

PMID- 15559882
TI  - Keys to success: pinpointing what works to improve hospital care.
AB  - In the quest to achieve better care, hospitals need to consider several factors
      that can mean the difference between success and failure. In a new report from
      the Commonwealth Fund, researchers sought to underscore these "ingredients for
      success" by studying what they considered four high-performing hospitals across
      the country: Beth Israel Deaconess Medical Center in Boston; El Camino Hospital
      in Mountain View, CA; Mission Hospitals in Asheville, NC; and Jefferson Regional
      Medical Center in Pittsburgh.

PMID- 15559883
TI  - Fighting obesity. Part 2: Evaluating weight-loss programs.

PMID- 15559884
TI  - Clinical weight-loss programs.

PMID- 15559885
TI  - Commercial weight-loss programs.

PMID- 15559886
TI  - Continuity of care: checklist for assessing compliance.

PMID- 15559887
TI  - Nutrition and Afghan culture.

PMID- 15559888
TI  - Warren A. Weinberg: pioneer in the field of learning disabilities.

PMID- 15559889
TI  - Dyslexia.

PMID- 15559890
TI  - Current status of treatments for dyslexia: critical review.
AB  - The acquisition of reading is a complex neurobiologic process. Identifying the
      most effective instruction and remedial intervention methods for children at risk
      of developing reading problems and for those who are already struggling is
      equally complex. This article aims to provide the clinician with a review of more
      current findings on the prevention and remediation of reading problems in
      children, along with an approach to considering the diagnosis and treatment of a
      child with dyslexia. The first part of the review describes interventions
      targeted at preventing reading difficulties in the at-risk younger child. The
      second part of the review discusses the efficacy of approaches to treat the
      older, reading-disabled child ("intervention studies"). Factors that impact the
      response to treatment are also discussed, as are neuroimaging studies that offer
      insight into how the brain responds to treatment interventions. With appropriate
      instruction, at-risk readers can become both accurate and fluent readers. In
      contrast, although intensive, evidence-based remedial interventions can markedly
      improve reading accuracy in older, reading-disabled children, they have been
      significantly less effective in closing the fluency gap. Owing to the dynamic
      course of language development and the changes in language demands over time,
      even after a child has demonstrated a substantial response to treatment
      interventions, his or her subsequent progress should be carefully tracked to
      ensure optimal progress toward the development of functional reading and written
      language skills.

PMID- 15559891
TI  - Using our current understanding of dyslexia to support early identification and
      intervention.
AB  - One of the major risk factors for reading disability is difficulty learning to
      read words in text in an accurate and fluent manner. This is apparent when a
      child at risk of dyslexia first starts to attempt to read. Dyslexic children
      struggle to grasp and automate the alphabetic principle (ie, they cannot "sound
      out" words or use phonemic decoding strategies) and therefore have difficulty
      deciphering unfamiliar words that they have not encountered before. Even though
      many of these words are part of the child's oral vocabulary, the child cannot
      recognize them in printed form. As a result, reading can be extremely laborious
      and time-consuming, fraught with errors, and altogether an unrewarding, aversive
      experience. To be an efficient reader, one must be able to rapidly and
      effortlessly recognize many words by sight, and for a child to acquire this
      facility requires multiple exposures to these words. The difficulty that dyslexic
      children have in developing reliable and efficient phonemic decoding ability
      makes the acquisition of a lexicon of sight words a much slower process than it
      is for the average reader. Several other factors can affect a child's ability to
      read, which are reviewed herein. However, early recognition and treatment of
      deficient phonologic awareness are an extremely important step in the prevention
      of a reading problem in the child who is at risk of dyslexia.

PMID- 15559892
TI  - Developmental dyscalculia.
AB  - Developmental dyscalculia is a specific learning disability affecting the normal
      acquisition of arithmetic skills. Genetic, neurobiologic, and epidemiologic
      evidence indicates that dyscalculia, like other learning disabilities, is a brain
      based disorder. However, poor teaching and environmental deprivation have also
      been implicated in its etiology. Because the neural network of both hemispheres
      comprises the substrate of normal arithmetic skills, dyscalculia can result from
      dysfunction of either hemisphere, although the left parietotemporal area is of
      particular significance. The prevalence of developmental dyscalculia is 5 to 6%
      in the school-aged population and is as common in girls as in boys. Dyscalculia
      can occur as a consequence of prematurity and low birthweight and is frequently
      encountered in a variety of neurologic disorders, such as attention-deficit
      hyperactivity disorder (ADHD), developmental language disorder, epilepsy, and
      fragile X syndrome. Developmental dyscalculia has proven to be a persisting
      learning disability, at least for the short term, in about half of affected
      preteen pupils. Educational interventions for dyscalculia range from rote
      learning of arithmetic facts to developing strategies for solving arithmetic
      exercises. The long-term prognosis of dyscalculia and the role of remediation in
      its outcome are yet to be determined.

PMID- 15559893
TI  - Neuroimaging in disorders of social and emotional functioning: what is the
      question?
AB  - Social and emotional processing uses neural systems involving structures ranging
      from the brain stem to the associational cortex. Neuroimaging research has
      attempted to identify abnormalities in components of these systems that would
      underlie the behavioral abnormalities seen in disorders of social and emotional
      processing, notably autism spectrum disorders, the focus of this review. However,
      the findings have been variable. The most replicated anatomic finding (a tendency
      toward large brains) is not modular, and metabolic imaging and functional imaging
      (although showing substantial atypicality in activation) are not consistent
      regarding specific anatomic sites. Moreover, autism spectrum disorder
      demonstrates substantial heterogeneity on multiple levels. Here evidence is
      marshaled from a review of neuroimaging data to support the claim that
      abnormalities in social and emotional processing on the autism spectrum are a
      consequence of systems disruptions in which the behaviors are a final common
      pathway and the focal findings can be variable, downstream of other pathogenetic
      mechanisms, and downstream of more pervasive abnormalities.

PMID- 15559894
TI  - Prefrontal executive function syndromes in children.
AB  - "Executive function" is a term describing the processes required for conscious
      control of thought, emotion, and action that are central to the management of
      one's day-to-day life. Executive function is subserved by the prefrontal cortex
      and related subcortical structures. Disorders affecting the prefrontal cortex
      subcortical system are numerous and heterogeneous, but contemporary research has
      begun to elucidate the mechanisms and consequences of dysfunction in various
      subsystems with increasing specificity. Prefrontal executive dysfunction results
      in impaired regulation of cognition, attention, behaviors, arousal, and emotion,
      all of which have serious and pervasive consequences for functioning across the
      life span. These executive function deficits are typically difficult to treat,
      ameliorate, or remediate and require sensitive handling by caretakers. Executive
      dysfunction can arise as a consequence of many different factors (metabolic,
      genetic, certain types of epilepsy, cerebral dysgenesis, prematurity, traumatic
      brain injury, hypoxia, and toxic exposure). The present review delineates the
      features of prefrontal executive function deficits in children and proposes a
      roadmap for their diagnosis, treatment, and management.

PMID- 15559895
TI  - Attention-deficit hyperactivity disorder (ADHD).
AB  - Approaches to the diagnosis and treatment of attention-deficit hyperactivity
      disorder (ADHD) are undergoing a major change as a result of information from
      studies on the genetics of ADHD and the use of new neuroimaging technologies.
      Moreover, pharmacogenomics, although still in its infancy, will provide a basis
      for much more sophisticated treatment strategies for ADHD, particularly once more
      information is available about the genetics of ADHD. Even at this point in time,
      there is some pertinent information available that, although not ready for
      application in clinical settings, nonetheless provides a broader perspective for
      the clinician. In terms of etiology, ADHD is a neuropsychiatric disorder. There
      is a genetic basis in about 80% of the cases, involving a number of different
      genes, and in about 20% of the cases, ADHD is the result of an acquired insult to
      the brain. Some individuals likely have both genetic and acquired forms. Although
      medication works well in many cases of ADHD, optimal treatment of ADHD requires
      integrated medical and behavioral treatment. The family plays a crucial role in
      the management of children with ADHD. Because there is often a very high degree
      of comorbidity between ADHD and learning disabilities, teachers also have a great
      deal to contribute in the day-to-day management of these children. Early
      recognition and treatment prevent the development of more serious psychopathology
      in adolescence and adulthood.

PMID- 15559896
TI  - Psychiatric implications of language disorders and learning disabilities: risks
      and management.
AB  - This article reviews the relationship between different learning disabilities,
      language disorders, and the psychiatric disorders that are commonly associated
      with learning disabilities and language disorder: attention-deficit hyperactivity
      disorder (ADHD), anxiety disorders, depression, and conduct or antisocial
      personality disorder. The complex associations between language disorders and
      specific learning disabilities--dyslexia, nonverbal learning disorder,
      dyscalculia--and the various psychiatric disorders are discussed. Clinical
      vignettes are presented to highlight the impact of these disorders on a child's
      social and psychological development and the importance of early recognition and
      treatment.

PMID- 15559897
TI  - Dyslexics have more fnu.

PMID- 15559898
TI  - Lessons learned in living with attention-deficit hyperactivity disorder.

PMID- 15559899
TI  - Helping children with nonverbal learning disability: what I have learned from
      living with nonverbal learning disability.

PMID- 15559900
TI  - From research to policy to practice: prescription for success for students with
      learning disabilities.
AB  - As a community, physicians with expertise in child development and an
      appreciation of school-related challenges are uniquely positioned to enhance the
      well-being of children with specific learning disabilities. Efforts in such areas
      as differential diagnosis, enhancing communication between home and school and
      among parents and related service providers, accountability for effective and
      timely intervention, advocacy, and the application of scientific approaches to
      instruction and progress monitoring are among the ways in which the medical
      community can support children with special learning needs.

PMID- 15559901
TI  - Relevance of neuroscience to effective education for students with reading and
      other learning disabilities.
AB  - New directions in educational assessment and instruction are supported by recent
      advances in the neurosciences. Among these are early identification of potential
      learning problems through brief, efficient assessments of specific language
      skills that predict later reading outcomes; early intervention that
      systematically targets critical linguistic processing skills; and the necessity
      of stimulating all functions of a reading, writing, or computing brain.

PMID- 15559902
TI  - The economics of the flu.

PMID- 15559903
TI  - The ultimate survivors? Reality TV bribes players to exercise and quit smoking.

PMID- 15559904
TI  - [IgA nephropathy (immunoglobulin A nephropathy, M.Berger). Main symptoms:
      (painless) macrohematuria or microhematuria].

PMID- 15559905
TI  - [What is your diagnosis? Probably arthritis reactive to Streptococcus
      pneumoniae].

PMID- 15559906
TI  - [Can suicidality be cured? Suicide prevention in the G.P.'s practice].
AB  - Annually, approximately 1300 people commit suicide in Switzerland. Whilst general
      practitioners play a crucial role in the prevention of suicide, suicidal patients
      are a huge burden on physicians. The risk factors for suicide are well known but
      a comprehensive assessment of the suicide risk calls for an evaluation of the
      individual resources. Most at risk are those who have previously attempted
      suicide; the risk of repetition remains elevated for years. Suicide in itself is
      not a disease but it is closely related to mental disorders. A critical issue in
      suicide prevention is the recognition and treatment of underlying disorders.
      Patients often refuse further therapy after an attempted suicide, probably due to
      communication problems between patients and mental health professionals. It will
      be demonstrated how it is nevertheless possible to establish a therapeutic
      alliance which would prove beneficial in a future crisis.

PMID- 15559907
TI  - [Elevated lipid levels during pregnancy--what to do?].
AB  - Based on a clinical case we discuss the physiological changes in the lipid
      metabolism during pregnancy. The changes are characterised by a marked elevation
      of the total plasma cholesterol and the triglyceride levels. Usually there is no
      need for a specific therapy.

PMID- 15559908
TI  - [CARDS confirms usefulness of LDL lowering in type 2 diabetics].

PMID- 15559909
TI  - [Multilocular painful urticarial plaques. Eosinophilic cellulitis (Wells
      syndrome)].

PMID- 15559910
TI  - [VALUE study underscores the importance of reaching goal blood pressure values
      for minimization of cardiovascular risks].

PMID- 15559911
TI  - [New study shows probiotics ineffective in prevention of post-antibiotic vaginal
      candidiasis].

PMID- 15559912
TI  - National Health Act, 2003--licence to practice--a step in the right direction?

PMID- 15559914
TI  - Asthma--a risk factor for dental caries.

PMID- 15559913
TI  - Resin-infiltrated-dentine--a FE-ESEM microscopy investigation.
AB  - The formation of a hybrid layer is essential for bonding of dental composites to
      dentine. The objective of this study was to examine the effects of various
      etchants/conditioners and dentine bonding systems on dentine surfaces utilising a
      Field Emission Environmental SEM (FE-ESEM). Twenty one, freshly extracted human
      molar teeth were utilised. Dentine without resin application was initially
      observed both wet and dried in the following conditions: (1) fractured surface,
      (2) smear layer, and (3) smear layer removed with 37% phosphoric acid. Resin
      infiltration into dentine was then studied after applying Scotchbond 1, Optibond
      Solo, Prime & Bond NT, or Prompt L-Pop systems. Scotchbond 1, Optibond Solo, and
      Prime & Bond NT resins penetrated the dentine tubules and created hybrid layers;
      although, in some cases Prime & Bond NT only created a partially filled hybrid
      layer. No polymerised resin or hybrid layer was observed for Prompt L-Pop. The FE
      ESEM permitted observation of specimens at near in-vivo wet conditions.

PMID- 15559915
TI  - Minimal intervention dentistry (MI) for South Africa.
AB  - The intention of Minimal Intervention Dentistry (MI) is to preserve as much tooth
      tissue as possible and to offer less threatening care to fearful patients. MI is
      based on a new understanding of cariology and the therapeutic value of biomimetic
      materials such as Glass lonomers. It has particular relevance to a new caries
      classification and employs treatment concepts such as selective caries removal
      and sealed restorations. The MI approach is appropriate for the vast majority of
      the population in South Africa; it addresses the public fear of dental treatment.
      It can be an effective private practice builder and is thus applicable to private
      and public services.

PMID- 15559916
TI  - An approach to a patient with dyspepsia.
AB  - Dyspepsia (indigestion) is a non-specific group symptoms related to the upper
      gastrointestinal tract. Organic disease must be detected and distinguished from
      non-"ulcer dyspepsia" or "functional" dyspepsia, so that specific treatment can
      be given.

PMID- 15559917
TI  - An approach to the patient with unexplained chest pain.
AB  - After coronary artery disease has been excluded as a cause for unexplained chest
      pain, oesophageal disease must be considered. Ambulatory pH monitoring reveals
      abnormal oesophageal acid exposure in 50% of patients with recurrent non-cardiac
      chest pain.

PMID- 15559918
TI  - Traveller's diarrhoea.
AB  - Dietary indiscretion is penalized by an increased risk of diarrhoea. Severe
      dehydration is seldom encountered, and fluid losses are easily corrected with
      readily available fluids. Drug treatment is either directed at suppressing the
      pathogen or for its anti-secretory effect.

PMID- 15559919
TI  - Helicobacter pylori in peptic ulcer disease.
AB  - Infection with Helicobacter pylori is very common throughout the world; causes
      chronic gastritis; predisposes to gastric and duodenal ulcers and is recognised
      as a class 1 gastric carcinogen. The disease has a relatively low mortality, but
      it results in substantial suffering and high economic costs.

PMID- 15559920
TI  - Caustic injury to the upper GI tract.
AB  - Caustic injury of the oesophagus and stomach is common among children and young
      adults. The morbidity associated with caustic injury can be severe. Due to
      improved management the mortality has decreased significantly. Alkaline agents
      tend to cause more severe injury than acidic agents.

PMID- 15559921
TI  - Essential oils for caries prevention: a viable option?

PMID- 15559922
TI  - General practitioner's radiology case 25. Unicystic ameloblastoma.

PMID- 15559924
TI  - Abstracts of the American Society for Cell Biology 44th Annual Meeting. December
      4-8, 2004, Washington, DC, USA.

PMID- 15559923
TI  - [Knee-bending and -stretching-spastic in infant cerebral palsy. Surgery aimed at
      functional improvement and its results].
AB  - Any treatment of disorders of the knee in patients with cerebral palsy is a
      complex task in terms of indications and surgical technique. Surgical management
      has the potential to considerably improve function in walkers as well as
      tetraparetic patients. The close functional relationship between the knee joint
      and the adjacent hip and ankle joints requires an integrated view. An increased
      anterior pelvic tilt aggravates any shortening of the hamstring muscles. An
      equinus foot deformity increases knee extensor movement. When evaluating
      postoperative results, it is never sufficient to indicate the postoperative range
      of motion only. Instead, functional evaluation criteria complemented by
      instrumented gait analysis must be used to define the results more quickly and to
      uncover postoperative problems.

PMID- 15559925
TI  - Are there long-term benefits of donepezil in Alzheimer's disease?

PMID- 15559926
TI  - Promoting rational use of medicines saves lives and money, WHO experts say.

PMID- 15559927
TI  - [Three consecutive operations for chronic subdural haemorrhage in an 87-year-old
      man].
AB  - We describe a man aged 87 with a subdural haemorrhage which needed to be
      evacuated three times over an eight-week period. After the third operation the
      patient's physical and cognitive performance increased markedly, even though his
      performance had been assessed as "normal for his age" during his illness. The
      case illustrates the impressive regenerative capacity of the aged brain, the
      challenge in differentiating between disease symptoms and age-associated
      functional decline, the difficulties in deciding when to operate on an old
      patient, and the importance of functional assessments in health care for the
      elderly.

PMID- 15559928
TI  - WHO leads drive for international co-ordination of clinical research.

PMID- 15559930
TI  - Selected bibliography.

PMID- 15559929
TI  - New meningitis threat being contained by web of partnerships.

PMID- 15559931
TI  - Townes and Holtfreter (1955): directed movements and selective adhesion of
      embryonic amphibian cells.

PMID- 15559932
TI  - LiCl inhibits the establishment of left-right asymmetry in larvae of the direct
      developing echinoid Peronella japonica.
AB  - The effect of LiCl on the establishment of left-right (LR) asymmetry in larvae of
      the direct-developing echinoid Peronella japonica was investigated with special
      attention to the location of the amniotic opening and ciliary band pattern. The
      larvae of echinoids are LR symmetric, but shortly before metamorphosis the larval
      LR symmetry is lost as a result of the formation of an amniotic cavity
      (vestibule), part of the adult rudiment, on the left side of the body. P.
      japonica has been considered to be the only exception among the echinoids,
      because the amniotic cavity forms at the midline of the larval body. In the
      present study we discovered the following two different LR asymmetric traits in
      larvae of P. japonica: the opening of the amniotic cavity initially forms at the
      midline of the larval body but shifts to the left dorsal side, and a looped
      ciliary band that initially forms with LR symmetry becomes LR asymmetric as a
      result of the formation of a bulge on left dorsal side. The establishment of LR
      asymmetry in both the location of the amniotic opening and the change in the
      shape of the ciliary band was influenced by exposing embryos to LiCl.
      Quantitative analysis of the shift in amniotic opening showed that exposure of
      embryos to LiCl causes repression of leftward shifting of the amniotic opening in
      earlier stage larvae, and leftward or rightward shifting in later stage larvae.
      These findings suggest that LiCl is an effective means of impairing the
      establishment of LR asymmetry in sea urchin embryos.

PMID- 15559933
TI  - Scaling effects on metabolism of a teleost.
AB  - Scaling effects on citrate synthase (CS), glucose-6-phosphate dehydrogenase (G6
      PDH), RNA. RNA/DNA ratio and protein contents of brain, liver and skeletal muscle
      were studied in a teleost, Clarias batrachus. The activity of white skeletal
      muscle CS decreased significantly as a function of increasing body mass of the
      fish. It shows that the fulfilment of energy demand in white skeletal muscle is
      not dependent on aerobic metabolism. The activity of liver G6-PDH decreased with
      the increasing body mass showing reduction in NADPH generation for lipogenic
      activity. However, increase in G6-PDH activity showed enhancement in reductive
      synthesis in skeletal muscle of the larger-sized individuals. A positive scaling
      of RNA, RNA/DNA ratio and protein contents reflects changes in macromolecular
      turnover for ATP-supplying enzymes and proteins.

PMID- 15559934
TI  - Species-specific effects on hemolymph glucose control by serotonin, dopamine, and
      L-enkephalin and their inhibitors in Squilla mantis and Astacus leptodactylus
      (crustacea).
AB  - Hemolymph glucose level is controlled by crustacean Hyperglycemic Hormone (cHH)
      released from the eyestalk neuroendocrine centers under conditions of both
      physiological and environmental stress. Biogenic amines and enkephalin have been
      found to mediate the release of several neurohormones from crustacean
      neuroendocrine tissue. We investigated the effect of serotonin, dopamine, and
      Leucine-enkephalin in vivo--injected into the stomatopod Squilla mantis and the
      decapod Astacus leptodactylus--whether increasing or depressing glycemia.
      Serotonin had a marked effect in elevating glucose level compared with initial
      values in both species. 5-HT1-like receptors are more involved in mediating
      serotonin action as co-injected cyproheptadine was a more effective antagonist
      than ketanserin (5-HT2-like receptor inhibitor). Dopamine injection in intact
      animals produced a decrease below initial levels of hemolymph glucose. This
      effect was significantly antagonized by domperidone. No significant effect of
      both amines occurred in eyestalkless animals. L-enkephalin shows a differential
      effect: in S. mantis it induced hypoglycemia while in A. leptodactylus it caused
      an increase of glucose level. Co-injected antagonist naloxone affected the
      direction of the response. Serotonin appears to provide a major control on
      glucose mobilization, whereas dopamine and L-enkephalin act as modulators whose
      plasticity in use or action varies among species.

PMID- 15559935
TI  - Diurnal rhythm and effect of temperature on oxygen consumption in earthworms,
      Amynthas gracilis and Pontoscolex corethrurus.
AB  - Different species of earthworms show distinct patterns of oxygen consumption
      pattern. Amynthas gracilis has a diurnal rhythm of oxygen consumption, consuming
      more oxygen at night, whether being incubated at 20, 25, or 30 degrees C. The
      higher oxygen consumption of A. gracilis is directly related to its behavior, as
      it shows higher activity at night. In contrast, Pontoscolex corethrurus showed no
      obvious diurnal rhythms of oxygen consumption or behavior. In addition, its
      oxygen demand is not related to temperature. A. gracilis has higher oxygen
      consumption than P. corethrurus at 20 and 30 degrees C. The difference in
      temperature adaptation of oxygen consumption between these two species may be a
      strategy by which earthworms adapt to different temperatures. This might explain
      why A. gracilis disperses on the soil surface at night after a rain, in contrast
      to P. corethrurus for which such behavior was not been observed.

PMID- 15559936
TI  - Seminal vesicle secretion of African catfish, its composition, its behaviour in
      water and saline solutions and its influence on gamete fertilizability.
AB  - The seminal vesicle secretion (SVS) of the African catfish, Clarias gariepinus,
      was investigated by analytical and experimental methods. SVS consists mainly of
      proteins and glycoproteins which are responsible for its viscous and sticky
      nature. The secretion contains also high activities of acid phosphatase, alkaline
      phosphatase, and proteases. These catabolic enzymes do not have functions in
      autolysis or liquefaction of SVS but are considered to eliminate aging
      spermatozoa from the proximal portions of seminal vesicle and from the spermatic
      duct. SVS of the African catfish is unstable in the environment relevant for
      natural spawning. When SVS was mixed with water, seminal plasma or different
      types of saline solutions its protein coagulated forming fibrous or granular
      particles of variable size within a few seconds. Pure SVS completely inhibited
      the motility as the sticky secretion hindered spermatozoa in free swimming. SVS
      had also a negative effect on sperm fertility, egg fertility, and sperm egg
      contact, as the fertilization was drastically suppressed in the presence of SVS.
      Basing on our analytical and experimental results we exclude that SVS has
      functions in stabilizing the viability of spermatozoa stored in the spermatic
      ducts or is an energy resource of spermatozoa. It also does not improve or
      stabilize the fertilization process and has no functions in adhering the eggs to
      substrates or in covering the eggs for mechanical protection or antibacterial
      defense. A function of SVS in the male and female communication during the
      prenuptial spawning behaviour is discussed.

PMID- 15559937
TI  - Nucleotide and protein sequences of a proteinase inhibitor from the vitelline
      envelope of dace (Tribolodon hakonensis) eggs.
AB  - Our experimental purpose is to probe the structure(s) of the chorionic proteinase
      inhibitor and its cDNA sequence(s) and to develop the application of safe
      medicines for protection of human and other animal bodies from pathogenic microbe
      attacks. In this study, chorionic proteinase inhibitor protein was isolated,
      sequenced and used to base the design of PCR primers, which were then used to
      amplify DNA using RT-PCR. A cDNA clone of the protein which inhibited the
      activities of serine proteinases and thermolysin was obtained on the basis of
      mRNA extracted from ovarian tissue of dace, Tribolodon hakonensis, and the
      deduced amino acid sequence was determined. Chorionic proteinase inhibitor
      (TribSPI) peptides of about 9.0 kDa (TribSPI) and 14 kDa (TribSPI-S) were
      purified from vitelline envelope extracts by thermolysin-immobilized affinity
      chromatography. The cloned TribSPI cDNA was 1806 bp in length, and the open
      reading flame (ORF) was 915 bp encoding a protein of 305 amino acid residues. The
      inhibitor protein had a molecular mass of 33,550 daltons and was composed of five
      similar domains. Each domain contained eight cysteine residues, and it's deduced
      amino acid sequence was only 33 approximately 34% identical to those of human and
      porcine antileukoproteinases (hALP and pALP, respectively). A possible binding
      site for serine proteinases, Arg-Ile, was contained in three domains.

PMID- 15559938
TI  - Na+ / H+ exchanger-3 is involved in mouse blastocyst formation.
AB  - The mouse blastocyst consists of the trophectoderm, the inner cell mass, and a
      fluid-filled cavity, the blastocoel. Formation and subsequent expansion of this
      cavity is important for further differentiation of the inner cell mass and
      successful implantation. Previous work provided evidence that vectorial transport
      of Na+ and CL- ions through the trophectoderm into the blastocoel generates an
      osmotic gradient that drives fluid across this epithelium. As the activity of the
      Na+ / H+ exchanger (NHE) has been implicated as the exchanger responsible for
      facilitating the transtrophectodermal Na+ flux, the functional role of NHE in
      mouse blastocoel development was determined. Embryos were cultured in the
      presence of subtype-specific NHE inhibitors to examine the role of NHEs in
      blastocoel development. When 2-cell stage embryos were treated continuously with
      a specific inhibitor of NHE-1, cariporide, the embryos passed beyond the 8-cell
      stage and became blastocysts. However, in the presence of a specific inhibitor of
      NHE-3, S3226, the 2-cell stage embryos developed to the morula stage but
      formation of the blastocyst were inhibited in a dose-dependent manner. Cariporide
      did not inhibit the formation of the blastocoel cavity from the morula stage
      whereas S3226 did inhibit that process. S3226 also reduced the rate of re
      expansion of blastocysts collapsed by cytochalasin D upon transfer to the control
      medium. An immunofluorescence study showed that NHE-3 was detected in the
      vicinity of the cell membrane of the trophectoderm, especially in the apical cell
      margins of the trophectoderm. These results suggest that NHE-3 is likely involved
      in blastocyst formation.

PMID- 15559939
TI  - Inducible reproductive plasticity of the guppy Poecilia reticulata in response to
      predation cues.
AB  - Predation has long been described as one of the major driving forces in
      evolution. Guppies (Poecilia reticulata) from natural populations exposed to
      different predation pressures, were found to have different life history traits.
      Reproductive plasticity in response to direct predation cues has mainly been
      reported for invertebrates. The goals of the present study were to determine
      whether exposure to predation cues would induce reproductive phenotypic
      plasticity in female guppies and to determine whether the effective cues are
      visual, chemical, or a combination of both. In our first experiment, female
      guppies exposed to predation cues of the african cichlids Aulonocara nyassae
      increased their reproductive output by almost two fold, having larger brood-sizes
      and shorter brood-interval at the first spawn. This effect disappeared in the
      second spawn in the absence of predators. In the second experiment we found that
      exposure to the predators induced an increase in the brood-size regardless of
      whether the cue was: only visual, only chemical, visual and chemical or visual,
      chemical and tactile. The impacts of these cues were equally powerful on the
      tested variables and they did not have any cumulative effect. Similar to the
      results of the first experiment, this effect disappeared in the second spawn, in
      the absence of predation cues. The present study demonstrates a direct immediate
      and reversible effect of predation cues on guppy reproduction.

PMID- 15559940
TI  - Yolk partitioning in embryos of the lizard, Calotes versicolor: maximize body
      size or save energy for later use?
AB  - The hatchlings of Calotes versicolor and other congeners retain residual yolk for
      immediate post-hatching needs. Excision of 8% yolk (approximately equal residual
      yolk) from the eggs resulted in smaller hatchlings when compared to those
      emerging from sham operated eggs. However, hatchlings in both groups retained the
      same amount of residual yolk. The findings suggest that residual yolk in
      hatchlings of C. versicolor is an important part of the energy budget set aside
      by developing embryos and that the advantages of large hatchling size are counter
      balanced by selection for residual yolk.

PMID- 15559941
TI  - Use of physical sciences in support of environmental management.
AB  - Offshore drilling for oil and gas has been conducted since the early 1900s. Oil
      and gas under the seabed continue to be an important part of the energy resources
      of the United States. The need to balance the value of these resources against
      the potential for environmental damage is an important concern. This article
      explains why and how the Minerals Management Service (MMS) of the US Department
      of the Interior uses research in physical sciences to help fulfill its
      environmental goals, and it provides background information on the role of
      physical sciences in decision-making for Outer Continental Shelf (OCS) oil, gas,
      and other minerals development. Established in the 1970s, the MMS' Environmental
      Studies Program is a highly focused marine research program designed to provide
      the environmental information necessary for OCS energy and nonenergy minerals
      planning and development activities. The physical sciences research supported by
      MMS includes physical oceanography, oil-spill risk analyses, atmospheric
      sciences, and sand and gravel studies. Instead of giving a comprehensive review
      on physical sciences research in MMS, this article presents sample MMS studies
      and illustrates how these studies are utilized to support decision-making in
      environmental management.

PMID- 15559942
TI  - Using goals in environmental management: the Swedish system of environmental
      objectives.
AB  - In Sweden, environmental policy is essentially carried out through a system of
      environmental objectives adopted by Parliament in the late 1990s. This system
      contains principles, objectives, interim targets, strategies, and follow-up
      mechanisms, which together provide a solid ground for increased efficiency and
      improved prioritization in environmental policies. Despite the ambitious approach
      of the Swedish Parliament, the system of environmental objectives suffers from
      certain shortcomings. Some of the objectives are imprecise and difficult to
      evaluate, and there are no rules or principles that may be used to solve goal
      conflicts and to prioritize between different objectives. As a consequence, the
      environmental objectives tend to differ in their degrees of operationalizability,
      and the priority-setting between different objectives is often unclear.

PMID- 15559943
TI  - Toward a sectorwide design for environment support system for the rail industry.
AB  - Rail has an important role to play in the development toward a sustainable
      transportation system. In this perspective, the European Brite Euram Project
      RAVEL (Rail Vehicle Eco-Efficient Design) has developed a rail sectorwide Design
      for Environment system to be used and standardized throughout the full supply
      chain. At the core of the system, quantitative environmental performance
      indicators for rail vehicles and components are used to incorporate environmental
      performance target levels in the product requirements and to measure and
      communicate achieved environmental performance. The concept of eco-efficiency is
      used to integrate both environmental and economical considerations. The
      methodology further builds on a standardized material list, standardized data
      formats, and proactive design guidance. To date, first steps are already taken to
      integrate the RAVEL project results into sector initiatives toward industrywide
      acceptance and standardization.

PMID- 15559944
TI  - Rockfall hazard and risk assessment along a transportation corridor in the Nera
      Valley, central Italy.
AB  - Rockfalls are a common type of fast-moving slope failures, and in many countries
      they represent the primary cause of landslide fatalities. We present a
      methodology to ascertain rockfall hazard and to determine the associated risk
      along transportation networks. The proposed methodology is based on the combined
      analysis of the recurrence of rockfall events, determined from historical
      information, the frequency-volume statistics of rockfalls, obtained from
      inventories of recent rockfall triggering events, and the results of a physically
      based, spatially distributed rockfall simulation model used to determine rockfall
      hazard. The available information on rockfall hazard is combined in a Geographic
      Information System with a map of the transportation network to identify the road
      sections potentially subject to rockfalls. Information on the location and type
      of rockfall defensive measures, including revetment nets, elastic fences,
      concrete walls, and artificial tunnels, is used to estimate the efficacy of the
      defensive structures and to determine the level of the residual rockfall risk
      along the roads. To illustrate the methodology, we discuss an application in a 48
      km2 area in the Nera River valley, in the Umbria Region of central Italy, where
      rockfalls are abundant, and where considerable investments were recently made to
      mitigate rockfall risk.

PMID- 15559945
TI  - Local government conservation and management of native vegetation in urban
      Australia.
AB  - Reflecting a worldwide trend of devolution of power and responsibilities to local
      authorities, metropolitan local governments in Australia now have a role in
      protecting and managing native vegetation (bushland). Reporting on questionnaire
      and interview results for Sydney, Melbourne, Perth, and Adelaide, this research
      examines the main disturbances in local government bushlands, local governments'
      efforts in bushland conservation, and universality of issues and responses among
      the cities and between urban and urban-rural local authorities. A number of
      disturbances in bushlands are common among the cities, with weeds, development
      impacts, and urban run off perceived to be the most threatening. Management
      efforts focus on weed control, whereas other main disturbances are receiving less
      attention. Community involvement in management is prevalent, although regional
      coordination among local governments is limited. Local governments are willing to
      be involved in biodiversity conservation and their capacity would be enhanced
      with increased funding, staffing, and regional coordination.

PMID- 15559946
TI  - Application of likelihood ratio and logistic regression models to landslide
      susceptibility mapping using GIS.
AB  - For landslide susceptibility mapping, this study applied and verified a Bayesian
      probability model, a likelihood ratio and statistical model, and logistic
      regression to Janghung, Korea, using a Geographic Information System (GIS).
      Landslide locations were identified in the study area from interpretation of IRS
      satellite imagery and field surveys; and a spatial database was constructed from
      topographic maps, soil type, forest cover, geology and land cover. The factors
      that influence landslide occurrence, such as slope gradient, slope aspect, and
      curvature of topography, were calculated from the topographic database. Soil
      texture, material, drainage, and effective depth were extracted from the soil
      database, while forest type, diameter, and density were extracted from the forest
      database. Land cover was classified from Landsat TM satellite imagery using
      unsupervised classification. The likelihood ratio and logistic regression
      coefficient were overlaid to determine each factor's rating for landslide
      susceptibility mapping. Then the landslide susceptibility map was verified and
      compared with known landslide locations. The logistic regression model had higher
      prediction accuracy than the likelihood ratio model. The method can be used to
      reduce hazards associated with landslides and to land cover planning.

PMID- 15559947
TI  - Uncertainty analysis in dissolved oxygen modeling in streams.
AB  - Uncertainty analysis in surface water quality modeling is an important issue.
      This paper presents a method based on the first-order reliability method (FORM)
      to assess the exceedance probability of a target dissolved oxygen concentration
      in a stream, using a Streeter-Phelps prototype model. Basic uncertainty in the
      input parameters is considered by representing them as random variables with
      prescribed probability distributions. Results obtained from FORM analysis
      compared well with those of the Monte Carlo simulation method. The analysis also
      presents the stochastic sensitivity of the probabilistic outcome in the form of
      uncertainty importance factors, and shows how they change with changing
      simulation time. Furthermore, a parametric sensitivity analysis was conducted to
      show the effect of selection of different probability distribution functions for
      the three most important parameters on the design point, exceedance probability,
      and importance factors.

PMID- 15559948
TI  - A hierarchical fuzzy decision support system for the environmental rehabilitation
      of Lake Koronia, Greece.
AB  - This article presents the design of a fuzzy decision support system (DSS) for the
      assessment of alternative strategies proposed for the restoration of Lake
      Koronia, Greece. Fuzzy estimates for the critical characteristics of the possible
      strategies, such as feasibility, environmental impact, implementation time, and
      costs are evaluated and supplied to the fuzzy DSS. Different weighting factors
      are assigned to the critical characteristics and the proposed strategies are
      ordered with respect to the system responses. The best strategies are selected
      and their expected impact on the ecosystem is evaluated with the aid of a fuzzy
      model of the lake. Sensitivity analysis and simulation results have shown that
      the proposed fuzzy DSS can serve as a valuable tool for the selection and
      evaluation of appropriate management actions.

PMID- 15559949
TI  - Adverse effects on Alfeios River Basin and an integrated management framework
      based on sustainability.
AB  - The Alfeios River, the longest and highest flow-rate river in Peloponnisos,
      constitutes an important water resource and ecosystem in Greece. In the present
      study, human activities in the Alfeios River Basin are described, and their
      impacts on water quality and the ecosystem are analyzed; effects resulting from
      interventions on river geomorphology between Flokas Dam and the river delta are
      determined. These actions have caused significant adverse impacts on the
      infrastructure (the dam, railroad, and road bridges), the level of aquifer water
      table and area water uses, and the aquatic and riparian ecosystem. A general
      integrated management strategy is formulated and a master management plan is
      proposed for resolving management problems in river basins. The plan considers
      local conditions and national requirements and complies with the European
      Communities legislation; it would help prevent further basin deterioration,
      improve water quality, and protect water resources and ecosystems in the area in
      accordance to sustainable development. The Alfeios River Basin serves as a case
      study in the development of the plan.

PMID- 15559950
TI  - Land conversion for suburban housing: A study of urbanization around Warsaw and
      Olsztyn, Poland.
AB  - In Poland of the 1990s, urban demand for housing land around city agglomerations
      increased rapidly. The decreasing profitability of agricultural production also
      caused farmers to become interested in the sale of agricultural land for
      nonagricultural purposes, and new land legislation granted them the right to sell
      their land. Polish counties simultaneously received self-governing status, which
      allowed them to define the priorities for local development. Counties received
      additional responsibility for land management and quickly demonstrated strong
      support for land conversion, which was perceived as a factor of local
      development. This paper argues that decentralization and the extension of private
      control over land have led to a loss of rural landscapes in Poland because
      farmers, county governments, and rural society in general gained from the
      conversion of agricultural to housing land. Rapid urbanization has significantly
      reduced the availability of open space around cities and threatened valuable
      landscapes, for it has occurred in the absence of environmental safeguards. This
      paper reports findings from research in two counties, located in regions with
      diverse economic growth rates. Decentralization is particularly problematic if
      tax regulations and intergovernmental fiscal relations reward local authorities
      for urbanization but not environmental protection.

PMID- 15559951
TI  - The use of irrigation water in Bulgaria's Plovdiv region during transition.
AB  - The amount of water Bulgaria uses for irrigation sharply declined during the
      transition. Large sections of the existing irrigation systems were abandoned, and
      those still in use are hardly maintained. Crops such as wheat and barley have
      replaced more water-intensive crops, such as vegetables, rice, and maize. This
      problem has an impact on the future development of agriculture and the allocation
      of the country's water resources. The central argument is that land fragmentation
      in the wake of decollectivization and restitution contributes to the irrigation
      systems' abandonment. This article focuses on the institutional factors involved,
      but also considers additional factors that might have influenced the process.
      Further, it examines the causes driving these changes and analyzes their effect
      on irrigation. It is based on a review of the relevant legislation as well as
      fieldwork in 17 villages located in the Plovdiv region of Bulgaria. The article
      concludes that institutional settings, in addition to changes in large-scale
      market forces and the state enforcement mechanism, have contributed to the
      irrigation decline in Bulgaria.

PMID- 15559953
TI  - Bibliography. Current world literature. Neuromuscular disease: nerve.

PMID- 15559952
TI  - Microcystic adenoma of the pancreas: clinical, radiologic, and cytologic
      features.
AB  - BACKGROUND: Cytology literature on pancreatic microcystic adenoma is sparse. It
      is important to separate microcystic adenoma from adenocarcinoma and mucinous
      cystic neoplasms on aspiration cytology, because patients with microcystic
      adenoma can be treated conservatively unless they are symptomatic. Potential
      pitfalls with endoscopic ultrasound (EUS) sampling of these lesions is discussed.
      METHODS: From January 1991 through June 2003, 10 patients with microcystic
      adenoma of the pancreas were diagnosed on fine-needle aspiration cytology. An
      additional patient, who was diagnosed with a mucinous cystic neoplasm by EUS
      sampling, was rediagnosed with microcystic adenoma on the excised specimen.
      Aspirate smears, cell blocks, core biopsies, subsequent excision (if any), and
      special stains were reviewed. Imaging studies and clinical data were available
      from the majority of patients. RESULTS:  CLINICAL RESULTS: The patients included
      5 females and 6 males who ranged in age from 45 years to 84 years. Radiology
      studies showed tumors, which were heterogeneous with areas of fluid density and
      septations, located in the head, body, or tail of the pancreas. The masses ranged
      in size from 1 cm to 17 cm. The radiographic impression was highly suggestive of
      microcystic adenoma in six patients; detailed radiologic information was not
      available from three patients. On follow-up, six patients were alive and well at
      the last follow-up available, two patients died of unrelated sepsis, and three
      patients were lost to follow-up. Three of 11 patients underwent a Whipple
      resection. Cytology results: The cytologic features identified included the
      following: 1) Bland tumor cells were seen in sheets or small groups with a lack
      of nuclear abnormalities and moderate-to-scant cytoplasm with occasional clearing
      or vacuolation. Naked nuclei were present occasionally. Tumor cells were
      distinguishable from acinar cells based on larger cell size and granular
      cytoplasm in which prominent nucleoli were seen. 2) Relatively acellular,
      fibrovascular stroma was seen, usually located between tumor cells. 3)
      Calcifications were seen in four of eleven tumors. One tumor sampled by EUS
      revealed fragments of glandular-type epithelium with minimal atypia and was
      diagnosed erroneously as a mucinous cystic neoplasm. Cell blocks or core biopsies
      from most tumors showed fragments of dense stroma and cystic spaces lined by
      flattened epithelial cells. Subsequent Whipple resection in three patients showed
      histologic features of microcystic adenoma. Special stains performed in select
      tumors were positive for cytokeratin, carbohydrate antigen 19.9, and periodic
      acid-Schiff stain. Calretinin staining was negative in the tumor cells.
      CONCLUSIONS: A cytologic diagnosis of microcystic adenoma is possible based on
      the criteria described above. Cell block and/or core biopsy, special stains, and
      radiologic information are key in making a definitive diagnosis. Patients with
      microcystic adenoma are spared a major surgical procedure unless they are
      symptomatic. With the EUS-guided modality of pancreatic sampling, caution should
      be exercised in misinterpreting benign glandular epithelium derived from the
      stomach or small bowel as a mucinous cystic neoplasm.

PMID- 15559954
TI  - Pneumatosinus dilatans, associated with meningioma; is remodeling of the skull
      base triggered by local cathepsin-expression? A case report (2004:8b).

PMID- 15559955
TI  - A pediatric limb mass (2004:11a).

PMID- 15559956
TI  - Retinoblastoma presenting as orbital cellulitis: report of four cases with a
      review of the literature.
AB  - PURPOSE: To analyze the clinical and histopathological features of retinoblastoma
      presenting as orbital cellulitis. MATERIAL AND METHODS: Retrospective analysis of
      case records and review of the histopathology of four patients with
      retinoblastoma presenting as orbital cellulitis.RES U LTS On histopathological
      examination, all eyes showed anterior segment involvement with extensive
      necrosis. One case had a well-differentiated tumor and one showed extraocular
      extension of the tumor. CONCLUSION: Advanced necrotic retinoblastoma with
      anterior segment involvement may often present as orbital cellulitis.

PMID- 15559957
TI  - Multiple thoracoabdominal calcifications in a healthy West African man.

PMID- 15559958
TI  - HIV-1 and HCV infections among antibody-negative blood donors.

PMID- 15559959
TI  - HIV-1 and HCV infections among antibody-negative blood donors.

PMID- 15559960
TI  - HIV-1 and HCV infections among antibody-negative blood donors.

PMID- 15559961
TI  - MRI in breast cancer.

PMID- 15559962
TI  - Hypocalciuric hypercalcemia and autoantibodies against the calcium-sensing
      receptor.

PMID- 15559963
TI  - More on blue cohosh and perinatal stroke.

PMID- 15559964
TI  - Code of Professional Conduct.

PMID- 15559965
TI  - Statement on the physician acting as an expert witness.

PMID- 15559966
TI  - [Re "Phantom study for the detection of simulated lesions in five different
      digital and one conventional mammography system"].

PMID- 15559967
TI  - Psychrophilic prokaryote structural-functional relationships, biogeography and
      evolution within marine sediment.
AB  - Prokaryote diversity has been found to be surprisingly high in cold marine
      sediments with numerous clades detected spread throughout many phyla. Marine
      benthic sediment clades are largely ecotypically distinct and autochthonous.
      Since almost all marine sediment prokaryotic taxa have yet to be cultivated,
      functionality is currently overwhelmingly cryptic for most benthic prokaryotic
      taxa except those falling into specific lineages for which there is cultivation
      or detailed biogeochemical data. Multivariate statistical comparisons of 16S rRNA
      gene sequence and denaturing gradient gel electrophoresis (DGGE) data show
      distinct distribution patterns of prokaryotic communities in sediment layers. By
      comparison geographical differences and differences related to the physical
      texture and organic content seem to result in generally smaller differences.

PMID- 15559968
TI  - Culture-independent analysis of bacterial species from an anaerobic mat from Lake
      Fryxell, Antarctica: prokaryotic diversity revisited.
AB  - Using a lake sediment mat sample from Lake Fryxell, Antarctica, different DNA
      extraction and purification methods were compared by denaturing gradient gel
      electrophoresis (DGGE). Based on the analyses of cloned 16S rRNA gene sequences a
      high degree of as yet uncultured prokaryotes have been reported in this sample.
      Although the vast majority of these as yet uncultured organisms seem to be
      classified as representatives of Firmicutes, Proteobacteria and Bacteriodetes,
      many of these taxa should be regarded novel species as judged from the distance
      of their gene sequences to those of their nearest cultured phylogenetic
      neighbours. The physiological properties of cultured strains from Lake Fryxell
      and of those of described species that are phylogenetically affiliated to the as
      yet uncultured species from this environment, suggest the presence of a well
      developed food web of primary producers, anaerobic degraders and fermenters, and
      aerobes. The few novel species described from this sample add to the increasing
      number of species characterized from various Antarctic habitats. Determination of
      the phylogenetic relatedness of the mat clone sequences of Clostridia with recent
      entries into public databases revealed that many of the putative species are
      closely related to other putative species detected in a broad range of
      environments, ranging from rumen and gut, anaerobic and polluted soil to sediment
      and groundwater samples.

PMID- 15559969
TI  - Bacterial diversity of a soil sample from Schirmacher Oasis, Antarctica.
AB  - The bacterial diversity of a soil sample collected in the vicinity of Lake Zub,
      Schirmacher Oasis, Antarctica, was determined both by establishing pure colonies
      of culturable bacteria and by cloning the total 16S rDNA of the soil and
      establishing the phylogeny of the clones. Analysis of the 16S rRNA gene clones
      indicated that the bacteria belonged to the classes alpha-proteobacteria, beta
      proteobacteria, gamma-proteobacteria, Gemmatimonas, Bacteriodetes,
      Actinobacteria, Chloroflexi and Chlamydiae. In addition, seven clones were
      categorized as unidentified and unculturable in the classes of beta
      Proteobacteria, Actinobacteria, Chloroflexi and Chlamydiae. Further, the
      culturable bacteria from the same site were identified as belonging to the genera
      Pseudomonas, Sphingobacterium, Arthrobacter, Micrococcus, Brevondimonas,
      Rhodococcus and Microbacterium. These results identify for the first time the
      presence of bacteria belonging to the genera Brevundimonas, Microbacterium,
      Rhodococcus, Serratia, Enterobacter, Rhodopseudomonas, Sphingomonas, Acidovorax,
      Burkholderia, Nevskia, Gemmatimonas, Xanthomonas and Flexibacter in Antarctica.
      Further, comparison of the Antarctic soil bacterial diversity with other cold
      habitats of Antarctica like from sediments, ice and cyanobacterial mat samples
      indicated that the bacterial diversity in soil was similar to the diversity
      observed in the continental shelf sediment sample. The Antarctic soil clones also
      resembled the bacterial diversity of soils from other geographical regions, but
      were unique in that none of the clones from the soil belonged to the uncultured
      Y, O, G, A and B groups common to all soil samples.

PMID- 15559970
TI  - A preliminary study of airborne microbial biodiversity over Peninsular
      Antarctica.
AB  - This study used PCR-based molecular biological identification techniques to
      examine the biodiversity of air sampled over Rothera Point (Antarctic Peninsula).
      16S rDNA fragments of 132 clones were sequenced and identified to reveal a range
      of microorganisms, including cyanobacteria, actinomycetes, diatom plastids and
      other uncultivated bacterial groups. Matches for microorganisms that would be
      considered evidence of human contamination were not found. The closest matches
      for many of the sequences were from Antarctic clones already in the databases or
      from other cold environments. Whilst the majority of the sequences are likely to
      be of local origin, back trajectory calculations showed that the sampled air may
      have travelled over the Antarctic Peninsula immediately prior to reaching the
      sample site. As a result, a proportion of the detected biota may be of non-local
      origin. Conventional identification methods based on propagule morphology or
      culture are often inadequate due to poor preservation of characteristic features
      or loss of viability during airbome transfer. The application of molecular
      biological techniques in describing airbome microbial biodiversity represents a
      major step forward in the study of airborne biota over Antarctica and in the
      distribution of microorganisms and propagules in the natural environment.

PMID- 15559971
TI  - Abundance and function of bacteria in the Southern Ocean.
AB  - The very low water temperatures existing in polar oceans that experience seasonal
      advance and retreat of pack ice do not inhibit the presence of large bacterial
      populations. Bacteria may contribute significantly to the energy transfers within
      the Southern Ocean. In the last decades, notable progress has been made in the
      knowledge of the role of marine bacteria in the Southern Ocean. A short overview
      of the abundance and function ofAntarctic marine bacteria is given, with respect
      to metabolic activity. The importance of spatial and temporal variability is
      described. The ecological function of Antarctic marine bacterioplankton is
      discussed. Depending on food web structure, bacteria may be either a link in food
      webs supporting metazoan production, or a sink where bacterial production is
      metabolised by microorganisms. In the more oligotrophic areas and during certain
      periods of the year bacterial biomass dominates phytoplankton. The microbial food
      web is therefore the dominant pathway for carbon and energy flow in Antarctic
      seawater.

PMID- 15559972
TI  - Psychrophilic versus psychrotolerant bacteria--occurrence and significance in
      polar and temperate marine habitats.
AB  - The numerical dominance and ecological role of psychrophilic bacteria in bottom
      sediments, sea ice, surface water and melt pools of the polar oceans were
      investigated using isolates, colony forming units (CFU) and metabolic activities.
      All sediment samples of the Southern Ocean studied showed a clear numerical
      dominance of cold-loving bacteria. In Arctic sediments underlying the influence
      of cold polar water bodies psychrophiles prevailed also but they were less
      dominant in sediments influenced by the warm Atlantic Water. A predominance of
      psychrophiles was further found in consolidated Antarctic sea ice as well as in
      multiyear Arctic sea ice and in melt pools on top of Arctic ice floes. A less
      uniform adaptation response was, however, met in polar surface waters. In the
      very northern part of the Fram Strait (Arctic Ocean) we found bacterial counts
      and activities at 1 degree C exceeding those at 22 degrees C. In surface water of
      the Weddell Sea (Southern Ocean) psychrophiles also dominated numerically in
      early autumn but the dominance declined obviously with the onset of winter-water
      and a decrease of chlorphyll a. Otherwise in surface water of the Southern Ocean
      CFUs were higher at 22 degrees C than at 1 degree C while activities were vice
      versa indicating at least a functional dominance of psychrophiles. Even in the
      temperate sediments of the German Bight true psychrophiles were present and a
      clear shift towards cold adapted communities in winter observed. Among the polar
      bacteria a more pronounced cold adaptation of Antarctic in comparison with Arctic
      isolates was obtained. The results and literature data indicate that stenothermic
      cold adapted bacteria play a significant role in the global marine environment.
      On the basis of the temperature response of our isolates from different habitats
      it is suggested to expand the definition of Morita in order to meet the cold
      adaptation strategies of the bacteria in the various cold habitats.

PMID- 15559973
TI  - Ecophysiology of psychrophilic and psychrotolerant microorganisms.
AB  - This review describes psychrophilic and psychrotolerant microorganisms, which are
      abundant in different kinds of environments. Their ecophysiological properties
      and strategies for survival are reviewed in relation to their occurrences in
      marine and terrestrial environments, with special reference to the deep-sea, the
      sea ice and the permafrost soils.

PMID- 15559974
TI  - Cyanobacteria in Antarctica: ecology, physiology and cold adaptation.
AB  - Cyanobacterial species composition of fresh water and terrestrial ecosystems and
      chemical environment of water in Schirmacher Oasis in Continental Antarctica was
      investigated. Over 35 species of cyanobacteria were recorded. Diazotrophic
      species both heterocystous and unicellular contributed more than half to the
      count except in lake ecosystem. The species composition varied among the fresh
      water as well as terrestrial ecosystems. The physico-chemical analyses of water
      revealed its poor nurient content which might have supported the growth of
      diazotrophic cyanobacteria in an Antarctic environment. Among the cyanobacteria
      Oscillatoria, Phormidium and Nostoc commune were the dominant flora in most of
      the habitats. The physiological characteristics of isolated cyanobacteria strains
      indicated that N2-fixation, nitrate uptake, nitrate-reduction, ammonium-uptake,
      GS-transferase activity and photosynthesis was unaffected at low temperature (5
      degrees C) which indicated low temperature adaptation for Antarctic
      cyanobacteria. This phenomenon was not evident in different strains of tropical
      origin. The temperature optima for N2-fixation for the different Antarctic
      cyanobacterial strains was in the range of 15-25 degrees C, nearly 10 degrees C
      lower than their respective reference strains of tropical origin. Similar results
      were obtained for cyanobacteria-moss association. The low endergonic activation
      energy exhibited by the above metabolic activities supported the view that
      cyanobacteria were adapted to Antarctic ecosystem.

PMID- 15559975
TI  - Siderotyping of Antarctic fluorescent Pseudomonas strains.
AB  - Five fluorescent Pseudomonas strains isolated from Antarctica have been
      previously recognized as producing three structurally different pyoverdines. In
      the present work, siderotyping procedures have been used to classify these
      strains, together with 1282 isolates of different origins, into siderovars. The
      strain biodiversity encountered within each siderovar, as well as the potential
      taxonomic value of the siderovars, are described and discussed. It is concluded
      that a majority of antarctic strains are commonly distributed worldwide. One
      strain, however, presenting a particular pyoverdine structure found in a unique
      other isolate, was apparently much more specific to cold environment.

PMID- 15559976
TI  - Biogeochemical features of lipids in endolithic microbial communities in the Ross
      Desert (McMurdo Dry Valleys), Antarctica.
AB  - Endolithic microbial communities inhabiting porous rocks in the cold, dry
      mountainous regions of Antarctica have been studied extensively as examples of
      life's adaptations to extreme environments. Here, we examine hydrocarbons and
      fatty acids occurring in these communities in order to clarify their
      biogeochemical features with respect to source organisms, microbial activity,
      fossilization processes and the influence of Gondwanaland sediments. Unusually,
      long-chain (>C19) n-alkanes and anteiso-alkanes were often the major hydrocarbons
      in the samples. A suite of n-alkanoic acids (n-C9-n-C32) and long-chain anteiso
      alkanoic acids (a-C20-a-C30) were found, along with short-chain iso- and anteiso
      alkanoic acids, and n-alkenoic acids. The relationship between long-chain n
      alkanoic acids (n-C20-n-C32) and long-chain anteiso-alkanoic acids suggests that
      these compounds probably originated from the same group of microorganisms, such
      as bacteria or endolithic lichens, under moderate pH conditions (pH 3-5).
      Relatively high trans/cis-C16:1 alkenoic acid ratios suggest the presence of
      unfavorable environmental conditions in the endolithic microbial habitat. Normal
      alkenoic/alkanoic acid ratios may be a useful marker for the fossilization of
      endolithic microbial communities. Thermally matured triterpanes and steranes from
      fossilized associations on Mount Fleming strongly suggest the presence of
      Gondwanaland sediments formed during Devonian and Jurassic (400-180 million years
      ago).

PMID- 15559977
TI  - The effect of low-temperature-induced DNA supercoiling on the expression of the
      desaturase genes in synechocystis.
AB  - Temperature-dependent changes in genomic DNA supercoiling might play an important
      role in temperature perception and responsive gene regulation. In the
      cyanobacterium Synechocystis, low temperatures induce the expression of the genes
      for fatty acid desaturases that introduce double bonds into acyl chains of lipid
      bound fatty acids, thus regulating the membrane fluidity. I studied the effects
      of low temperature on supercoiling of the genomic DNA region that contains the
      regulatory elements of the desB gene for the omega3 desaturase, which is strongly
      induced by cold. Upon decrease in temperature, the degree of DNA supercoiling
      increased in this region. Novobiocin, an inhibitor of the DNA gyrase, prevented
      low-temperature-induced changes in DNA supercoiling and affected the expression
      of several desaturase genes with the most effect on desB. Decreasing in
      temperature induces three genes of FA desaturases encoding delta12, delta6 and
      omega3 desaturases in Synechocystis cells. Novobiocin inhibited completely low
      temperature-induced transcription of desB, accumulation of the corresponding
      protein, and the formation of the omega3 unsaturated fatty acids. In the presence
      of novobiocin, the novobiocin-resistant mutant cells of Synechocystis responded
      to the low-temperature treatment in the same way as the wild-type cells in the
      absence of the antibiotics. Thus, temperature-induced changes in DNA supercoiling
      might form an essential part of a global regulation pathway leading to low
      temperature acclimation in this mesophilic cyanobacterium.

PMID- 15559978
TI  - Characterization of RNA-binding properties of three types of RNA-binding proteins
      in Anabaena sp. PPC 7120.
AB  - The Rbp proteins in cyanobacteria are RNA-binding proteins with a single RNA
      recognition motif or RRM. A comprehensive assembly of genomic data suggests that
      there are two major classes of Rbp proteins (classes I and II) that diverged
      before the diversification of cyanobacteria. Class I proteins are further
      classified into two types with or without a C-terminal glycine-rich domain. The
      results of selection from a random RNA pool suggest that RbpA1 (class I) has
      affinity to C-rich and G-rich sequences. In vitro RNA binding assay with
      homopolymers indicated that class II protein has low affinity to poly(G) in
      contrast with class I proteins. Site-specific mutagenesis analysis of the RRM in
      RbpA1 showed that the aromatic residues Tyr4 or Phe46 are important in RNA
      binding as well as maintenance of secondary structure. We also tested various
      truncated proteins lacking the C-terminal domain as well as point mutants. Most
      of these proteins exhibited decreased affinity to RNA. Circular dichroism
      analysis as well as chromatographic analysis showed that Tyr4 and Phe46 are also
      important in maintaining the structure of RbpA1 protein. The C-terminal glycine
      rich domain itself does not contribute much to the RNA-binding, but Arg83 which
      is located close to the C-terminal end of RRM is important in the RNA-binding.

PMID- 15559979
TI  - Role of membrane lipid fatty acids in cold adaptation.
AB  - Psychrophilic and psychrotolerant bacteria have evolved various strategies to
      adapt to low temperature. One important strategy, which is crucial to the
      survival of the cell at low temperature, relates to the ability of the cell to
      modulate the fluidity of the membrane. Bacteria in general modulate membrane
      fluidity by altering their fatty acid composition. But, bacteria could also
      achieve the same by various other strategies such as by altering the lipid head
      group, the protein content of the membrane, the type of carotenoids synthesized,
      the fatty acid chain length and the proportion of cis to trans fatty acids. In
      addition bacteria have a two-component signal transduction pathway consisting of
      a membrane-bound sensor and a soluble cytoplasmic response regulator involved in
      the perception and transduction of low temperature signals. This review on cold
      adaptation highlights the various strategies by which bacteria modulate the
      fluidity of the membrane and the process by which it senses and transduces the
      low temperature signal.

PMID- 15559980
TI  - A perspective on cold enzymes: current knowledge and frequently asked questions.
AB  - Studies on psychrophilic enzymes to determine the structural features important
      for cold-activity have attracted increased attention in the last few years. This
      enhanced interest is due to the attractive properties of such proteins, i.e. a
      high specific activity and a low thermal stability, and thus, these enzymes
      constitute a tremendous potential for fundamental research and biotechnological
      applications. This review examines the impact of low temperatures on life, the
      diversity of adaptation to counteract these effects and gives an overview of the
      features proposed to account for low thermal stability and cold-activity,
      following the chronological order of the catalytic cycle phases. Moreover, we
      present an overview of recent techniques used in the analysis of the flexibility
      of a protein structure which is an important concept in cold-adaptation; an
      overview of biotechnological potential of psychrophilic enzymes and finally, a
      few frequently asked questions about cold-adaptation and their possible answers.

PMID- 15559981
TI  - Improved activity and stability of alkaline phosphatases from psychrophilic and
      mesophilic organisms by chemically modifying aliphatic or amino groups using
      tetracarboxy-benzophenone derivatives.
AB  - The activity-stability-structure relationship of the cold-active alkaline
      phosphatase from Red Arctic shrimp, Pandalus borealis (SAP) was studied by
      chemically modifying aliphatic (C-H) or amino (NH2) groups using benzophenone
      tetracarboxylic derivatives in either a light (UV-A) or dark reaction. The
      response of the cold-adapted enzyme was compared to a similarly modified calf
      alkaline phosphatase (CAP). MALDI-TOF-MS was used to determine the extent and
      nature of the modifications in both SAP and CAP. On average 2 to 4 amino acid
      residues were linked to a BP-modifier, with up to 18 to 21 amino acids modified
      in a smaller portion of the material. The effect of the modifications on kinetic
      and thermodynamic properties varied with the enzyme and type of modification. The
      aliphatic-group modified SAP demonstrated typical characteristics of a mesophilic
      enzyme, consistent with an activity-stability trade-off where gain in
      thermostability was attained at the expense of decreased activity. In contrast,
      the activity of the amino-group modified SAP attained an even more psychrophilic
      character with respect to its kinetic (increase in kcat and Km) and thermodynamic
      (reduction in deltaH#) properties. Interestingly, the amino-group modified SAP
      also acquired higher thermostability, thus demonstrating that both activity and
      stability can be simultaneously enhanced using chemical modification. The study
      demonstrates the applicability of benzophenone chemical modification for
      improving the thermal properties of enzymes from psychrophiles and mesophiles.

PMID- 15559982
TI  - Invisible war wounds.

PMID- 15559983
TI  - Cone-beam tomography with discrete data sets.
AB  - Sufficiency conditions for cone-beam data are well known for the case of
      continuous data collection along a cone-vertex curve with continuous detectors.
      These continuous conditions are inadequate for real-world data where discrete
      vertex geometries and discrete detector arrays are used. In this paper we present
      a theoretical formulation of cone-beam tomography with arbitrary discrete arrays
      of detectors and vertices. The theory models the imaging system as a linear
      continuous-to-discrete mapping and represents the continuous object exactly as a
      Fourier series. The reconstruction problem is posed as the estimation of some
      subset of the Fourier coefficients. The main goal of the theory is to determine
      which Fourier coefficients can be reliably determined from the data delivered by
      a specific discrete design. A Fourier component will be well determined by the
      data if it satisfies two conditions: it makes a strong contribution to the data,
      and this contribution is relatively independent of the contribution of other
      Fourier components. To make these considerations precise, we introduce a concept
      called the cross-talk matrix. A diagonal element of this matrix measures the
      strength of a Fourier component in the data, while an off-diagonal element
      quantifies the dependence or aliasing of two different components. One reasonable
      approach to system design is to attempt to make the diagonal elements of this
      matrix large and the off-diagonal elements small for some set of Fourier
      components. If this goal can be achieved, simple linear reconstruction algorithms
      are available for estimating the Fourier coefficients. To illustrate the
      usefulness of this approach, numerical results on the cross-talk matrix are
      presented for different discrete geometries derived from a continuous helical
      vertex orbit, and simulated images reconstructed with two linear algorithms are
      presented.

PMID- 15559984
TI  - Ultrabroadband self-phase-stabilized pulses by difference-frequency generation.
AB  - Ultrabroadband near-IR (800-1700-nm) pulses are obtained by type II difference
      frequency generation (DFG) between two synchronized noncollinear optical
      parametric amplifiers. Self-stabilization of the carrier-envelope offset phase,
      as expected from the DFG process, is demonstrated experimentally.

PMID- 15559985
TI  - Defense responses of Fusarium oxysporum to 2,4-diacetylphloroglucinol, a broad
      spectrum antibiotic produced by Pseudomonas fluorescens.
AB  - A collection of 76 plant-pathogenic and 41 saprophytic Fusarium oxysporum strains
      was screened for sensitivity to 2,4-diacetylphloroglucinol (2,4-DAPG), a broad
      spectrum antibiotic produced by multiple strains of antagonistic Pseudomonas
      fluorescens. Approximately 17% of the F. oxysporum strains were relatively
      tolerant to high 2,4-DAPG concentrations. Tolerance to 2,4-DAPG did not correlate
      with the geographic origin of the strains, formae speciales, intergenic spacer
      (IGS) group, or fusaric acid production levels. Biochemical analysis showed that
      18 of 20 tolerant F. oxysporum strains were capable of metabolizing 2,4-DAPG. For
      two tolerant strains, analysis by mass spectrometry indicated that deacetylation
      of 2,4-DAPG to the less fungitoxic derivatives monoacetylphloroglucinol and
      phloroglucinol is among the initial mechanisms of 2,4-DAPG degradation.
      Production of fusaric acid, a known inhibitor of 2,4-DAPG biosynthesis in P.
      fluorescens, differed considerably among both 2,4-DAPG-sensitive and -tolerant F.
      oxysporum strains, indicating that fusaric acid production may be as important
      for 2,4-DAPG-sensitive as for -tolerant F. oxysporum strains. Whether 2,4-DAPG
      triggers fusaric acid production was studied for six F. oxysporum strains; 2,4
      DAPG had no significant effect on fusaric acid production in four strains. In two
      strains, however, sublethal concentrations of 2,4-DAPG either enhanced or
      significantly decreased fusaric acid production. The implications of 2,4-DAPG
      degradation, the distribution of this trait within F. oxysporum and other plant
      pathogenic fungi, and the consequences for the efficacy of biological control are
      discussed.

PMID- 15559986
TI  - The orthodontic global positioning system.

PMID- 15559987
TI  - Effects of hypervaccination with bovine herpesvirus type 1 gE-deleted marker
      vaccines on the serological response and virological status of calves challenged
      with wild-type virus.
AB  - Twenty-four calves were immunised four times with gE-deleted infectious bovine
      rhinotracheitis marker vaccines before being challenged with small doses of wild
      type bovine herpesvirus type 1 (BHV-1). The repeated vaccinations induced strong
      immunity that prevented detectable virus replication and gE-seroconversion after
      the challenge infection in most of the calves. The hypervaccinated calves that
      shed virus after the challenge infection showed no delay in gE-seroconversion
      compared with unvaccinated control calves. Using a sensitive nested PCR, BHV-1 gE
      sequences could be detected in the trigeminal ganglia of several of the gE
      seronegative, challenge-infected calves, possibly indicating the presence of wild
      type BHV-1 DNA.

PMID- 15559988
TI  - Novel Cul/tributyl phosphine catalyst for amination of aryl chlorides.

PMID- 15559989
TI  - [Abstracts of the 79th Annual Meeting of the French Society of Surgical
      Orthopedics and Trauma].

PMID- 15559990
TI  - Selected papers from the Eleventh International Symposium on Recent Advances in
      Drug Delivery Systems and Controlled Release Society Winter Symposium. March 3-6,
      2003. Salt Lake City, Utah, USA.

PMID- 15559991
TI  - Ultraviolet and laser radiation safety.
AB  - Both ultraviolet radiation and laser radiation occupy pmt of the Spectrum
      designated "optical radiation". Thus, measurement techniques are similar and the
      same organs (eyes and skin) are at risk from accidental exposure. However, the
      equipment used to produce ultraviolet and laser radiation differs substantially
      and the harm caused by each type of radiation is also different. Another
      significant difference arises from the fact that ultraviolet radiation is natural
      with associated general population exposure. Consequently, the present article
      reviews the current status of both ultraviolet and laser radiation with the
      material divided into two sections where each hazard is considered separately.

PMID- 15559992
TI  - Recombinant protein production with prokaryotic and eukaryotic cells. A
      comparative view on host physiology. Proceedings of a symposium. November, 2002.
      Cernobbio, Italy.

PMID- 15559993
TI  - Dielectric studies of native, unfolded and intermediate forms of beta-lactamase.
AB  - Time-domain dielectric spectroscopy has been applied to native, intermediate and
      unfolded beta -lactamase structures both in the hydrated solid state and in
      solution. Gravimetric and dielectric measurements indicate that nearly three
      times as many water molecules are multiply hydrogen bonded to the unfolded
      compared with the native protein. By contrast, the primary hydration population
      of the state A intermediate is only 20% larger than that of the folded enzyme.
      Analysis of the beta -dispersions in terms of rotational relaxation of the
      protein's permanent dipole has indicated that there is no significant difference
      in the dimensions of the three structures. This is not consistent with the
      findings of previous studies employing different experimental techniques.

PMID- 15559994
TI  - A deconvolution method for evaluating indicator-dilution curves.
AB  - Characteristics of blood flow in tissue can be measured by administering an
      intravascular tracer and then deconvolving and analysing the resulting indicator
      dilution curves. Existing deconvolution methods are not typically generalizable
      to a variety of tissues. The authors have developed a more general deconvolution
      method using simulated indicator-dilution data. This method involves filtering
      the Fourier transform of indicator-dilution data with a modification of the
      Wiener filter, an adaptive deconvolution filter. Unlike the Wiener filter, this
      adaptive filter requires no previous knowledge of the noise frequency spectrum;
      it is derived by varying the magnitude of the noise spectrum until the
      oscillations in the deconvolved data fall below an optimal value. The optimal
      value corresponds to the setting of the noise spectrum that allows the most
      accurate and precise measurement of vascular characteristics from deconvolved
      data. Vascular characteristics measured in brain tissues using this deconvolution
      method on actual indicator-dilution data were similar to established values. It
      should be possible to use this method on time-concentration data collected from a
      variety of tissues using a number of different tracer measurement techniques,
      thereby allowing the accurate characterization of vascular physiology.

PMID- 15559995
TI  - A museum of words: History of the anatomical language of ENT and head and neck.

PMID- 15559996
TI  - Erythrocyte sedimentation rate studies in whole human blood.
AB  - Precise measurements have been made of the rate of sedimentation of whole blood
      in which the concentrations of red blood cells and the plasma proteins have been
      systematically varied. The contribution of each factor to the sedimentation
      process is expressed in terms of three parameters that describe the sedimentation
      curve: the set-up time, and the slopes of the first and second phases of
      settling. This analysis affords delineation between the onset and the degree of
      aggregation of the red blood cells as contributors to the usual ESR value, the
      height of plasma in a 200 nm blood column after 60 min. In terms of the 60 min
      ESR value, an increase in the haematocrit or albumin concentration inhibits
      sedimentation, the latter only slightly, whereas an increase in the concentration
      of globulin or fibrinogen accelerates sedimentation, with fibrinogen showing the
      more marked effect.

PMID- 15559997
TI  - Response of thermoluminescent lithium fluoride (TLD-100) to photon beams of 275,
      400, 500, 600, 730, 900, 1200, 1500, and 2500 eV.
AB  - LiF:Mg,Ti (TLD-100) extruded ribbons and cleaved crystals were exposed to
      monoenergetic photons of 275-2550 eV energy to determine their potential
      usefulness as radiation dosimeters for radiobiology experiments at these
      energies. The radiation source was synchrotron radiation from the 1 GeV electron
      storage ring, Aladdin. The authors report TLD response and glow curves for He-
      and air-annealed dosimeters. The undesirable effects of air annealing increase
      with decreasing photon penetration in the dosimeter. Under certain experimental
      conditions, UV radiation produced anomalous bleaching of high-temperature traps.
      The crystals and the chips presented a supralinear response, Supralinearity
      factors were determined to be of the order of 1.5 for crystals, and 1.7 for the
      chips. The authors' results indicate that TLDs are a reliable means to monitor
      the total energy deposited in irradiated cells and are now used routinely for
      radiobiology cell irradiations.

PMID- 15559998
TI  - Ion exchange, adsorption/desorption processes and related separation techniques.
      Proceedings of the 16th International Symposium on Preparative and Process
      Chromatography. June 29-July 2, 2003. San Francisco, California, USA.

PMID- 15559999
TI  - Optimum parameters in a model for tumour control probability including
      interpatient heterogeneity.
AB  - A model for computing tumour control probability (TCP) is studied which embodies
      a dependence on the size of the irradiated volume, the density of clonogenic
      cells and the dose received, together with the alpha and beta parameters of the
      linear quadratic model of cell kill. The model can be used to describe situations
      where both the dose and the clonogenic cell densities are inhomogeneously
      distributed; however there is still uncertainty about its radiobiological
      parameters and the author aims to establish parameters for four types of tumour.
      In its simplest form, when the volumes are spherical, the clonogenic cell density
      is considered constant throughout the volume and the dose is uniform, the model
      has been used (by D.J. Brenner, 1993) to predict the radiobiological parameter
      alpha which allows the model to best fit the observed clinical data for four
      types of tumour. Here a new set of fits to the data presented by Brenner is
      constructed using a model which includes the distribution of radiosensitivity
      across a heterogeneous patient population. It is shown that this leads to a
      different set of optimum radiobiological parameters when the clonogenic cell
      density is of the order of 107 cells cm-3.

PMID- 15560000
TI  - Effect of fiducial marker localization on stereotactic target coordinate
      calculation in CT slices and radiographs.
AB  - Novel methods are presented which allow the estimation of the effect of
      stereotactic fiducial marker localization on target localization in a
      stereotactic surgery planning program based on the integration of image data from
      various modalities. The results of simulations are presented. A method for the
      evaluation of the effect of fiducial marker localization error on stereotactic
      localization, both for computed tomography (CT) and digitized radiography. Is
      proposed based on perturbation studies. For tomographic data, the comparison of
      the stability of two types of fiducial localizers: a standard commercial device
      based on nine (six vertical and three oblique) rods and an imaginary system with
      an extra set of rods, called '4-N', is discussed. Results of the perturbation
      studies clearly indicate the necessity of sub-pixel registration of the fiducial
      markers in CT. On the other hand, results demonstrate that stereotactic
      localization based on projection images is less sensitive to fiducial
      localization error than CT. Finally, the authors present an algorithm for the
      localization of fiducial markers to sub-pixel accuracy in radiographs acquired
      with a commercial angio localizer.

PMID- 15560001
TI  - A robust method of multileaf collimator (MLC) leaf-configuration verification.
AB  - Presents a novel and robust method for leaf-position verification with a
      multileaf collimator (MLC). On the portal image associated with an MLC-generated
      treatment field, all true treatment-held-edge lines are either parallel or
      perpendicular to each other. This unique feature of an MLC treatment field has
      been fully exploited by the authors' method. Employing a Hough-type
      transformation as an edge-line-orientation detector and a chamfer-matching
      method, the authors can find the best matching parameters (including translation,
      rotation and scaling) adaptively between a prescribed MLC leaf configuration and
      the actual treatment-held edges generated by the MLC system. This works even if
      the portal image is partially corrupted by noise or covered by compact bony
      structures. Comparing these parameters with clinically accepted tolerances, the
      authors can make a "go-or-no-go" decision quickly.

PMID- 15560002
TI  - Proceedings of the 6th International Conference on Carbonic Anhydrases. June,
      2003. Bratislava, Slovak Republic.

PMID- 15560003
TI  - Retraction statement. Effect of burn injury on glucocorticoid receptor binding
      activity in rat muscle.

PMID- 15560004
TI  - The influence of inhomogeneous volume conductor models on the ECG and the MCG.
AB  - The authors investigated the influence of human body inhomogeneities such as the
      lungs, blood masses and the skeletal muscle layer on the electrical body surface
      potential and the magnetic field. The surface potentials and magnetic fields are
      calculated using a boundary element method. As a rule the blood masses have a
      large influence on both potential and magnetic field amplitude as well as on the
      potential and magnetic field map orientation, but the influence on the topology
      of the map is less in the electric case than in the magnetic case. The single
      dipole reconstruction was applied to estimate the error caused by neglecting
      inner inhomogeneities in source localization. The neglect of lungs and blood
      masses results in a localization error of less than 1 cm in the electric case but
      more than 1 cm for deep sources at the posterior side of the heart in the
      magnetic case. The authors tried to assess the influence of the skeletal muscle
      layer by both an analytical two-layered anisotropic half-space model and the
      torso extension method. The skeletal muscle layer causes a smoothing effect on
      the electrical surface potential and to a lesser extent on the magnetic field,
      leading to an overestimation of the actual source depth of about 1-2 cm. In
      principle this can be reduced by taking data from all over the thoracic surface.
      The authors designed experiments for simultaneous measurement of body surface
      potential and extracorporeal magnetic field from the same subject. The evaluation
      of data from two patients showing Wolff-Parkinson-White syndrome has shown that
      localization results from electric potential data and magnetocardiographic data
      are consistent.

PMID- 15560005
TI  - Image alignment by integrated rotational and translational transformation matrix.
AB  - Presents an algorithm to align 2D images with similar densitometric patterns in
      the spatial domain. It performs automatic identification of control points
      through local maxima in normalized image cross correlations computed through
      projections of an image function on 2D orthonormal bases over a predefined
      circular domain. The image is subsequently subjected to translational and
      rotational corrections through an integrated transformation matrix obtained by
      the least-squares minimization technique. The algorithm restricts the corrections
      required for alignment to rotation and translation only, and care is taken to see
      that the image does not go through scaling (isotropic or anisotropic) or
      nonlinear distortions. The least-squares method results in implicit equations in
      three variables, theta , h, upsilon , representing rotation, and translations
      along x and y axes. The present algorithm, on the other hand, is based on an
      approximation that results in a set of explicit equations that are easy to solve.
      The mathematical validity of this approximation is proved and the results
      obtained show that the algorithm performs well with similar biological
      (histological, autoradiographic, and tomographic) images. The algorithm is
      iterative, and its computer implementation is discussed.

PMID- 15560006
TI  - Dual-energy digital mammography utilizing stimulated phosphor computed
      radiography.
AB  - Dual-energy subtraction is a radiographic technique for the acquisition of a
      material selective image by the weighted subtraction of low- and high-energy
      digital X-ray images. This is achieved by exploiting the energy dependence of the
      X-ray attenuation components in the image. This can allow the removal of
      background morphology to enhance the presentation of otherwise obscured details.
      The detection of microcalcifications in a mammogram by dual-energy techniques has
      previously been investigated. These investigations indicated that, using dual
      energy techniques, small microcalcifications could be extracted from the
      background breast morphology with sufficient signal to noise ratio (SNR) to be
      full visualized. The authors present the extension of a theoretical dual-energy
      model to incorporate practical considerations and then compare the results with
      experimentally derived data using a commercially available computed radiography
      system. In particular the extended model now takes into account the energy
      dependent detective quantum efficiency of a system. This is thought to be a major
      factor in reducing the efficiency of dual-energy mammography. The theoretical
      model predicts that dual-exposure dual-energy mammography, utilizing HRIII image
      plates, could not provide a detail SNR of five for calcifications smaller than
      470 mu m. The experimental results verify this and indicate that dual-energy
      subtraction mammography, utilizing computed radiography, is currently not a
      viable technique for the detection of clinically significant microcalcifications.
      Further advances in X-ray image detector efficiency will be required if the full
      potential of this technique is to be achieved.

PMID- 15560007
TI  - A projection access order for speedy convergence of ART (algebraic reconstruction
      technique): a multilevel scheme for computed tomography.
AB  - The practical performance of algebraic reconstruction techniques (ART) for
      computed tomography (CT) depends heavily on the order in which the projections
      are considered. Complete orthogonalization, notwithstanding its theoretical
      justification, is not feasible because the computational time is prohibitive. The
      authors report here a scheme that yields the most efficient reconstruction
      without orthogonalization: projections are organized and accessed in a nominally
      multilevel fashion. Each level makes the best use of the image information
      reconstructed in the preceding levels. If the number of projections is a power of
      two. Then the access orders are exactly that for the 1D FFT. The authors' scheme
      can be easily implemented. Using it, one iteration of ART yields a high-quality
      image. Experimental results of this algorithm are demonstrated and compared with
      the results from the conventional sequential method and also random ordering.
      Comparisons show that this scheme is superior. ART is better in image quality
      than the Fourier back-projection algorithm, at least for a smaller number of
      projections. Since the authors have made it much more efficient in computational
      speed, ART could now find widespread use in medical imaging.

PMID- 15560008
TI  - An analytical approach to quantitative reconstruction of non-uniform attenuated
      brain SPECT.
AB  - An analytical approach to quantitative brain SPECT (single-photon-emission
      computed tomography) with non-uniform attenuation is developed. The approach
      formulates accurately the projection-transform equation as a summation of primary
      and scatter-photon contributions. The scatter contribution can be estimated
      using the multiple-energy-window samples and removed from the primary-energy
      window data by subtraction. The approach models the primary contribution as a
      convolution of the attenuated source and the detector-response kernel at a
      constant depth from the detector with the central-ray approximation. The
      attenuated Radon transform of the source can be efficiently deconvolved using the
      depth-frequency relation. The approach inverts exactly the attenuated Radon
      transform by Fourier transforms and series expansions. The performance of the
      analytical approach was studied for both uniform- and non-uniform-attenuation
      cases, and compared to the conventional FBP (filtered-backprojection) method by
      computer simulations. A patient brain X-ray image was acquired by a CT (computed
      tomography) scanner and converted to the object-specific attenuation map for 140
      keV energy. The mathematical Hoffman brain phantom was used to simulate the
      emission source and was resized such that it was completely surrounded by the
      skull of the CT attenuation map. The detector-response kernel was obtained from
      measurements of a point source at several depths in air from a parallel-hole
      collimator of a SPECT camera. The projection data were simulated from the object
      specific attenuating source including the depth-dependent detector response.
      Quantitative improvement (>5%) in reconstructing the data was demonstrated with
      the nonuniform attenuation compensation, as compared to the uniform attenuation
      correction and the conventional FBP reconstruction. The commuting time was less
      than 5 min on an HP/730 desktop computer for an image array of 1282*32 from 128
      projections of 128*32 size.

PMID- 15560009
TI  - Attenuation correction for three-dimensional PET using uncollimated flood-source
      transmission measurements.
AB  - An attenuation-correction method for three-dimensional PET imaging, which obtains
      attenuation-correction factors from transmission measurements using an
      uncollimated flood source, is described. This correction is demonstrated for two
      different phantoms using transmission data acquired with QPET, a rotating imaging
      system with two planar detectors developed for imaging small volumes. The scatter
      amplitude in the transmission projections was a maximum of 30%; to obtain
      accurate attenuation-correction factors the scatter distribution was first
      calculated and subtracted. The attenuation-corrected emission images for both
      phantoms indicate that their original uniform amplitudes have been restored. The
      attenuation correction adds only a small amount of noise to the emission images,
      as evaluated from the standard deviation over a central region. For the first
      phantom, with maximum attenuation of 48%, the noise added was 2.6%. The second
      phantom was attenuated by a maximum of 37%, and 1.9% noise was added. Because the
      transmission data are smoothed, some artifacts are visible at the edges of the
      phantom where the correction factors change abruptly within the emission image.

PMID- 15560010
TI  - Thomas C. Suhoff, MD, of the University of Texas Southwestern Medical Center at
      Dallas wins Bristol-Myers Squibb Neuroscience Research Award.

PMID- 15560011
TI  - Scatter correction for three-dimensional PET based on an analytic model dependent
      on source and attenuating object.
AB  - Three-dimensional positron emission tomography admits a significant scatter
      fraction due to the large aperture of the detectors, and requires accurate
      scatter subtraction. A scatter-correction method, applicable to both emission and
      transmission imaging, calculates the projections of the single-scatter
      distribution, using an approximate image of the source and attenuating object.
      The scatter background is subtracted in projection space for transmission data
      and in image space for emission data, yielding corrected attenuation and emission
      images. The accuracy of this single-scatter distribution is validated for the
      authors' small imaging system by comparison with Monte Carlo simulations. The
      correction is demonstrated using transmission and emission data obtained from
      measurements on the authors' QPET imaging system using two acrylic phantoms. For
      the transmission data, generated with a flood source, errors of up to 24% in the
      linear attenuation coefficients resulted with no scatter subtraction, but the
      correction yielded an accurate value of mu =0.11+or-0.01 cm-1. For the emission
      data, the corrected images show that the scattered background has been removed to
      within the level of the background noise outside the source. The residual
      amplitude within a cold spot in one of the phantoms was reduced from 21% to 3% of
      the image amplitude.

PMID- 15560012
TI  - New estimation methods that directly use the time accumulated counts in the input
      function in quantitative dynamic PET studies.
AB  - In cardiac dynamic PET studies, the input function can be obtained directly from
      the reconstructed images. Therefore, there is a need to convert the time
      accumulated count to the time-activity curve (TAC). Conventionally, this is done
      by dividing the total counts in a localized region on the reconstructed image
      obtained during each scan frame period by its frame duration. This conversion,
      however, can significantly bias the estimates of rate constants of a
      compartmental model describing the dynamics of a PET tracer. Three new methods
      are formulated in this study. These new methods either use the accumulated counts
      in the input function directly or convert the accumulated counts to the input
      function more accurately. Computer simulation results show, for C-11 acetate and
      F-18 fluoro-2-deoxy-D-glucose (FDG), that the three new methods proposed can
      improve significantly the parameter estimates over the ones obtained by the
      conventional method.

PMID- 15560013
TI  - A proof that uniform dose gives the greatest TCP for fixed integral dose in the
      planning target volume.
AB  - In this note it is shown that for a fixed integral dose to the planning target
      volume, the highest tumour control probability (TCP) arises when the dose is
      spatially uniform. This 'uniform dose theorem' is proved both for (i) a specific
      TCP model based on Poisson/independent voxel statistics, and (ii) any model for
      voxel control probability having a specific shape with respect to increasing
      dose.

PMID- 15560014
TI  - Uncertainty in delivered dose resulting from the distribution of source
      activities in a Selectron LDR afterloader.
AB  - The uncertainty in the delivered dose resulting from the distribution of 137Cs
      source activity in a clinical Selectron LDR unit has been studied. A comparison
      is made of the dose delivered to a point 'A' in an implant with sources of equal
      activity to the actual dose delivered in the same implant with source activities
      randomly chosen from the population in the afterloader.

PMID- 15560015
TI  - 133Xe for the in vivo X-ray fluorescence measurement of platinum.
AB  - In vivo measurements of platinum are important for studying the pharmacokinetics
      of platinum-based cytotoxic drugs. The technique of in vivo X-ray fluorescence
      can be utilized for such measurements. The feasibility of using 133Xe in near
      backscatter (almost 180 degrees ) geometry has been investigated and results
      compared to phantom measurements made using 99Tcm in the same experimental set
      up. An improvement in minimum detection limits is observed for all phantom depths
      less than 25 mm.

PMID- 15560016
TI  - Abstracts of the 33rd Conference of EDTNA/ERCA. Geneva, Switzerland, 4-7
      September 2004.

PMID- 15560017
TI  - Straight from the heart. Patients to be informed of mortality rates.

PMID- 15560018
TI  - Abstracts of the Southern Medical Association's 98th Annual Scientific Assembly.
      New Orleans, Louisiana, USA, November 11-13, 2004.

PMID- 15560019
TI  - Highlights of the year in JACC 2003.

PMID- 15560020
TI  - Use of laser energy during endodontic surgical procedures.

PMID- 15560021
TI  - Abstracts of the 22nd World Congress on Endourology and SWL and the 20th Basic
      Research Symposium. November 2-5, 2004, Mumbai, India.

PMID- 15560023
TI  - Abstracts of the NAASO (North American Association for the Study of Obesity)
      Annual Meeting. November 14-18, 2004, Las Vegas, Nevada, USA.

PMID- 15560022
TI  - Radiation oncology.

PMID- 15560024
TI  - Orthotics and prosthetics.

PMID- 15560025
TI  - Proceedings of the 27th Congress of the German Society of Transfusion Medicine
      and Immuno-Hematology. 19-22 October 1994, Saarbrucken, Germany.

PMID- 15560026
TI  - Abstracts of the 10th Meeting of the European Society for Haemapheresis (ESFH)
      and the 28th Congress of the German Society of Transfusion Medicine and Immuno
      Hematology (DGTI). Vienna, Austria, 17-20 September 1995.

PMID- 15560027
TI  - Trouble with doubles.

PMID- 15560028
TI  - Confronting child abuse.

PMID- 15560029
TI  - Overview of chronic cholestatic conditions in adults: terminology and
      definitions.
AB  - The cholangiopathies represent diseases and syndromes affecting the biliary
      system at any site between the canals of Hering and the ampulla of Vater. Hepato
      canalicular cholestasis reflects biliary secretory failure of the hepatocyte
      caused by disturbances of intracellular organelles or damage to the bile
      canalicular excretory functions. Drug reactions are related especially to
      antibiotics, phenothiazine derivates and carbamazepine. Immune-mediated
      cholangiopathies cause destruction and reduction of interlobular bile ducts, and
      are sometimes called vanishing bile duct diseases. They include primary biliary
      cirrhosis, primary sclerosing cholangitis, autoimmune cholangitis, chronic
      hepatic allograft rejection, graft-versus-host disease and chronic cholestatic
      sarcoidosis. Ischemic (vascular) cholangiopathies include traumatic, hepatic
      arteritis and mechanical causes. Infectious cholangiopathies usually are
      associated with the immunosuppressed patient.

PMID- 15560030
TI  - Pathogenesis of primary biliary cirrhosis, primary sclerosing cholangitis, and
      autoimmune cholangiopathy.
AB  - Autoimmune liver diseases have much in common with each other, and there are
      clear associations with genetic haplotypes. Elegant studies have shown autoimmune
      liver disease induced by viruses and drugs. Although there is evidence for
      nonimmunological events precipitating immune disease, especially in primary
      sclerosing cholangitis, the precise pathways, what is bystander and what is
      essential, have not been determined. This article reviews some of the mechanisms
      involved in pathogenesis.

PMID- 15560031
TI  - Histopathology of chronic cholestasis and adult ductopenic syndrome.
AB  - This article reviews the histopathologic liver alterations in chronic cholestatic
      diseases and parenchymal changes associated with periportal ductular reaction and
      fibrosis, which may result in end-stage biliary cirrhosis. Adult ductopenic
      diseases are possible causes of such chronic cholestasis. Ductopenia is defined,
      and guidelines are given for its quantitation. The last section summarizes the
      specific histologic lesions of primary biliary cirrhosis, primary sclerosing
      cholangitis, their histologic mimics, and the differential diagnosis with drug
      induced cholestasis and ductopenia.

PMID- 15560032
TI  - Primary biliary cirrhosis: clinical and associated autoimmune features and
      natural history.
AB  - Primary biliary cirrhosis, a chronic liver disease, predominately affects middle
      aged women. The diagnosis is established by the presence of disease-specific
      autoantibodies and compatible liver histology showing focal immune-mediated
      damage to the intrahepatic bile ducts. Patients now are detected prior to the
      onset of symptoms typical of cholestasis with abnormal liver function tests, or
      even prior to the onset of abnormal liver function tests, with positive
      antimitochondrial antibodies. Earlier diagnosis is changing not only our
      appreciation of the prevalence of this condition, but also of the natural
      history. The disease appears to be heterogeneous with some patients having a slow
      progression and a normal life-expectancy, although other patients have a more
      aggressive course developing symptoms and end-stage disease that leads to death
      or liver transplantation.

PMID- 15560033
TI  - Clinical features in primary sclerosing cholangitis.
AB  - This article describes clinical features in primary sclerosing cholangitis,
      including clinical presentation and complications. The natural history of the
      disease is discussed, as well as the strong association to inflammatory bowel
      disease.

PMID- 15560034
TI  - Autoimmune cholangitis.
AB  - Autoimmune cholangitis is the term that has been used to describe patients who
      have the clinical, biochemical, and histologic characteristics of primary biliary
      cirrhosis (PBC), but who are antinuclear antibody positive rather than anti
      mitochondrial antibody (AMA) positive in their sera. The course of their disease
      is similar to AMA positive cases, and the associated nonhepatic autoimmune
      diseases are the same in both AMA-positive and AMA-negative PBC. Serial testing
      for AMA using highly sensitive and specific techniques over time suggests that in
      subjects with autoimmune cholangitis, their AMA negative status remains negative.
      The beneficial response to treatment with ursodeoxycholic acid is the same as for
      AMA-positive PBC. It may be preferable to use the term autoimmune cholangitis,
      further stratified by AMA status, instead of the somewhat innapropriate term
      primary biliary cirrhosis.

PMID- 15560035
TI  - Predictive models of natural history in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis is a slow, progressive disease. Although many years may
      elapse before asymptomatic primary biliary cirrhosis patients begin experiencing
      symptoms of liver disease, their overall survival is significantly lower than the
      normal population. The Mayo natural history model has been developed to depict
      patient survival in the absence of effective therapeutic intervention. Although
      there are a number of caveats in applying this model, it has been validated using
      external data sets and established as an accepted tool for clinical or research
      purposes. Furthermore, recent data suggest that the Mayo natural history model
      continues to provide useful, predictive information in the presence of
      ursodeoxycholic acid therapy, which has been shown to lower the serum bilirubin
      to the natural history model for patient survival. In addition to the natural
      history model for patient survival, mathematical models have been developed to
      describe histologic progression and development of esophageal varices.

PMID- 15560036
TI  - Management of primary biliary cirrhosis and autoimmune cholangitis.
AB  - Several drugs have been evaluated in the treatment of primary biliary cirrhosis
      over a number of years. These drugs have immunosuppressive, antiinflammatory,
      cupruretic, antifibrotic and bile acid properties. Ursodeoxycholic acid has been
      shown to improve survival free of transplantation in a conclusive fashion. This
      drug is the single agent that can be recommended for the treatment of primary
      biliary cirrhosis. Corticosteroid therapy and ursodeoxycholic acid have been
      evaluated in a few patients with autoimmune cholangitis. This article reviews a
      large number of studies that have been published assessing different drugs in the
      treatment of these two entities, particularly in the treatment of primary biliary
      cirrhosis.

PMID- 15560037
TI  - The management of primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a chronic cholestatic liver disease
      characterized by a progressive, obliterating fibrosis of the intrahepatic and
      extrahepatic bile ducts. The pathogenesis of PSC is unknown, but it is thought to
      be an immune-mediated disease. Although the role of cupruretics,
      immunosuppressants (corticosteroids, azathioprine, tacrolimus, methotrexate),
      antifibrogenic agents, and ursodeoxycholic acid in the treatment of primary
      sclerosing cholangitis is reviewed, none of these agents has been shown to retard
      or reverse the rate of disease progression. Of these therapies, ursodeoxycholic
      acid at high doses looks the most promising, but large trials are needed to
      establish whether treatment with high-dose ursodeoxycholic acid influences the
      morbidity and mortality associated with primary sclerosing cholangitis.

PMID- 15560038
TI  - Lipids and lipid-activated vitamins in chronic cholestatic diseases.
AB  - Primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune
      cholangiopathy are cholestatic liver diseases of unknown cause. Destruction of
      small to medium bile ducts (in primary biliary cirrhosis and autoimmune
      cholangiopathy) and large bile ducts (in primary sclerosing cholangitis) leads to
      progressive cholestasis, liver failure and end-stage liver disease. A variety of
      abnormalities in lipid metabolism have been described in primary biliary
      cirrhosis, and range from alterations in serum lipid levels and lipoprotein
      subsets to deranged metabolism of cholesterol. Progressive cholestasis and,
      consequently, decreased small intestinal bile acid concentrations in these
      cholestatic liver disease can also lead to impaired absorption of fats and fat
      soluble vitamins, resulting in steatorrhea and deficiencies in vitamins A, D, E,
      and K. This article focuses on abnormalities in lipid metabolism in primary
      biliary cirrhosis and primary sclerosing cholangitis, and on lipid-activated
      vitamin deficiencies in these disorders.

PMID- 15560039
TI  - The pruritus of cholestasis: evolving pathogenic concepts suggest new therapeutic
      options.
AB  - Pruritus is a distressing symptom experienced by a large proportion of patients
      with cholestasis. The cause of this form of pruritus is unknown, and therapy
      tends to be empirical and unsatisfactory. This article discusses the emerging
      role of the brain and neurotransmitter systems in the pathogenesis of the
      pruritus of cholestasis and emphasizes the importance of the application of
      quantitative methodology in clinical trials of therapies for the pruritus of
      cholestasis.

PMID- 15560040
TI  - Osteoporosis.
AB  - Osteopenia, in the form of osteoporosis, is a common complication of chronic
      cholestatic liver diseases and, although its cause is poorly understood, it
      appears to be intimately related to the cholestasis itself. With more patients
      surviving longer with successful liver transplantation, the clinical significance
      of such osteopenia has increased, and a traumatic fracturing has become a major
      cause of morbidity in this patient population. Noninvasive diagnosis is easy, and
      serial measurements allow assessment of disease progression. Although no
      effective therapy can treat or prevent this complication, supportive measures can
      improve skeletal well-being, especially in high-risk individuals who are
      candidates for liver transplantation.

PMID- 15560041
TI  - Recurrence of primary biliary cirrhosis, autoimmune cholangitis and primary
      sclerosing cholangitis after liver transplantation.
AB  - Given the usually prolonged natural history of primary biliary cirrhosis,
      autoimmune cholangitis, and primary sclerosing cholangitis, and the relatively
      recent introduction of orthotopic liver transplantation, our understanding of
      recurrence of these autoimmune diseases after orthotopic liver transplantation
      has been slow to evolve. Present data suggest that after orthotopic liver
      transplantation, patients with primary biliary cirrhosis will have persistence of
      serum antimitochondrial antibodies, develop histologic lesions suggestive of
      recurrent primary biliary cirrhosis with a frequency in the 8% to 16% range at 2
      to 5 years after orthotopic liver transplantation, but will demonstrate little if
      any symptomatic disease as a consequence. Although data are extremely limited,
      autoimmune cholangitis patients will have a similar post-transplant course
      (without antimitochondrial antibodies). Recurrence of primary sclerosing
      cholangitis remains the most controversial, however, these patients probably
      develop nonanastomotic intrahepatic and extrahepatic strictures more frequently
      than patients without primary sclerosing cholangitis, with a frequency in the 20%
      to 25% range at 3 to 5 years. With longer patient follow-up and additional
      studies, it is hoped that our understanding of recurrent autoimmune biliary
      diseases will grow considerably in the future.

PMID- 15560042
TI  - Hepatobiliary malignancy.
AB  - Chronic cholestatic liver disease may be complicated by hepatobiliary malignancy.
      The early detection of hepatocellular carcinoma and cholangiocarcinoma is of
      paramount importance in the evaluation of candidates for liver transplantation,
      which remains the only effective treatment modality for advanced primary biliary
      cirrhosis and primary sclerosing cholangitis. This article reviews the
      identification of patients at high risk, current techniques for diagnosis, and
      makes recommendations for screening high-risk patients. This article also reviews
      preliminary data from the Mayo Clinic regarding liver transplantation for
      cholangiocarcinoma following radiation therapy.

PMID- 15560043
TI  - Metabolic liver disease in the pediatric patient.
AB  - Most metabolic liver diseases that affect pediatric patients present in the
      neonatal period with either cholestasis or acute liver failure. Metabolic liver
      disease in the older child has considerable overlap with adult patients. New
      diagnostic methods and therapy, including liver transplantation, has radically
      changed the outcome of many metabolic liver diseases.

PMID- 15560044
TI  - Wilson's disease.
AB  - Wilson's disease is an autosomal, recessive-inherited disorder of impaired
      biliary copper excretion that results in the accumulation of copper in various
      organs including the liver, the cornea and the brain. The Wilson's disease gene
      on chromosome 13 codes for a copper transporting P-type ATPase-ATP7B. More than
      60 mutations of this gene have been described. The diagnosis of Wilson's disease
      is based on clinical findings and laboratory abnormalities and can be made if two
      of the following symptoms are present: Kayser-Fleischer rings; topical neurologic
      symptoms; and low serum ceruloplasmin levels. In less typical cases diagnosis
      requires various other tests of copper metabolism. Effective medical treatment
      with copper chelators (D-penicillamine, trientine) or zinc results in symptomatic
      improvement and normal life expectancy. Orthotopic liver transplantation is
      indicated in advanced cases with hepatic decompensation or in patients with
      fulminant Wilson's disease.

PMID- 15560045
TI  - Liver disease in cystic fibrosis.
AB  - CF is a common hereditary disorder of ion transport, with increasing numbers of
      patients surviving beyond childhood and developing manifestations of
      hepatobiliary involvement. Inspissated secretions within the biliary tree result
      in obstruction and periductular inflammation that eventually progresses to focal
      and then multilobular cirrhosis. Fatty infiltration of the liver and hepatomegaly
      is common. Variceal hemorrhage and other findings of portal hypertension may be
      the initial presentation. At present, therapy with high-dose ursodeoxycholic acid
      should be considered standard, as it has been shown repeatedly to reduce the
      injurious effects of the cholestasis. Liver transplantation has been successfully
      performed on those with advanced disease and adequate pulmonary function.
      Innovative therapies for CF, including gene transfer, appear promising in
      preliminary studies, offering hope that earlier intervention in the course of
      hepatobiliary CF may soon be possible.

PMID- 15560046
TI  - Iron overload states.
AB  - Hereditary hemochromatosis is a common disorder of iron metabolism that
      increasingly is diagnosed and treated prior to the development of cirrhosis or
      diabetes. The discovery of a candidate gene for hereditary hemochromatosis
      undoubtedly will result in improved diagnosis of hereditary hemochromatosis and
      to a better understanding of certain aspects of iron absorption, hepatic iron
      uptake and release, and whole body iron metabolism. In turn, this enhanced
      understanding of iron biology can be applied to the observations seen in patients
      with other hepatic diseases such as chronic viral hepatitis.

PMID- 15560047
TI  - Hepatic porphyrias.
AB  - The porphyrias are metabolic disorders characterized by abnormal heme
      biosynthesis with excessive accumulation and excretion of porphyrias or porphyrin
      precursors. Defects in the enzymes of the heme biosynthetic pathway result in
      porphyria. Several of the disorders have been classified as hepatic because the
      major site of the biochemical defect has been localized to the liver. This
      article describes the enzymes of the heme biosynthetic pathway, the clinical
      features of the hepatic porphyrias and management of the disorders.

PMID- 15560048
TI  - Alcoholic liver disease.
AB  - Alcohol has been implicated in the genesis of liver disease for centuries.
      Significant progress has been made in our understanding of the pathogenesis of
      ALD. It is now apparent that both the consumption and the metabolism of alcohol
      promote the production of inflammatory mediators (cytokines) that result in
      hepatotoxicity and fibrogenesis. With time, this leads to progressively severe
      liver injury and, eventually, causes cirrhosis. Unfortunately, effective
      therapies for most individuals with ALD have not been found. High per capita
      consumption of alcohol, coupled with the dearth of effective treatments and the
      failure of most affected individuals to abstain from alcohol, explains why ALD is
      one of the most prevalent forms of disabling, chronic liver disease in the United
      States.

PMID- 15560049
TI  - Diabetes and the hepatobiliary system.
AB  - Diabetes mellitus can lead to metabolic changes that alter normal hepatic and
      biliary function and structure. These alterations in hepatic and biliary function
      and structure are usually benign, but in certain situations lead to significant,
      disabling disease. This article reviews the hepatic and biliary complications of
      diabetes, with emphasis on epidemiology, diagnosis, and management, as well as
      the glucose intolerance seen in liver disease.

PMID- 15560050
TI  - Liver dysfunction and parenteral nutritional therapies.
AB  - Hepatobiliary dysfunction associated with the use of total parenteral nutrition
      is a commonly recognized phenomenon occurring in up to 90% of patients on long
      term therapy. Reasons for these abnormalities, both supported by research as well
      as theoretical possibilities are explored. Practical guidelines considered useful
      in documenting, preventing and treating serious hepatic consequences of total
      parenteral nutrition are discussed. The role of combined liver and small bowel
      transplantation as treatment for select patients is also reviewed.

PMID- 15560051
TI  - Nonalcoholic steatohepatitis.
AB  - NASH is an important form of chronic liver disease that is increasingly
      recognized. The diagnosis is secured by biopsy findings with similarities to
      alcoholic hepatitis in a patient with a confirmed history of abstinence. Obesity
      is a major risk factor, but the disease also occurs in the nonobese. In 20% to
      40% of patients the disease can progress to various stages of fibrosis and
      ultimately cause cirrhosis and death from end-stage liver disease. For this
      reason, recognition of NASH is important, and establishing the diagnosis provides
      a further impetus for performing a liver biopsy as part of the evaluation of
      unexplained liver abnormalities. The mainstay of treatment is weight reduction in
      the obese. For those individuals who are not obese, continued observation is the
      only option currently available. Patients who develop decompensated cirrhosis
      should be considered for liver transplantation unless advanced age or other
      underlying medical illnesses are a problem. With the increasing knowledge about
      the pathophysiology of hepatic steatosis, it is hoped that better diagnostic
      tests for specific causes of NASH will be available and lead to efficacious
      therapy.

PMID- 15560052
TI  - Liver disease associated with alpha1-antitrypsin deficiency.
AB  - Alpha1-ATD is the most common metabolic liver disease in children for which liver
      transplantation is performed and, in adults, is associated with cirrhosis,
      hepatocellular carcinoma, and emphysema. It appears that only a proportion of
      patients with the deficiency develop clinical manifestations of this disease.
      Moreover, recent characterization of specific cellular and physiologic events
      have provided the basis for future potential therapeutic interventions.

PMID- 15560053
TI  - Adult liver transplantation for metabolic liver disease.
AB  - Liver replacement provides an effective method of replacing a failing liver, and
      corrects the underlying defect in many metabolic conditions. Results of liver
      transplantation for metabolic diseases have been encouraging, with the exception
      of hereditary hemochromatosis, in which infectious and for which cardiac
      complications appear to increase posttransplant mortality. An improved
      understanding of the underlying genetic and molecular defect will lead to
      advances in medical therapy and perhaps will decrease the need for liver
      replacement. The prospects of gene therapy are being pursued for many metabolic
      disorders, however until this research leads to direct clinical application,
      liver transplantation remains the only effective option for many patients with
      metabolic liver disease.

PMID- 15560054
TI  - Virology of hepatitis C virus.
AB  - Advances in molecular biology techniques have allowed the cloning of HCV and the
      characterization of this virus. This article provides a short summary of our
      current knowledge on the genomic organization of HCV, the implications of its
      genetic heterogeneous nature, and the probable replication strategy of this
      virus.

PMID- 15560055
TI  - Pathogenesis of hepatocellular damage in chronic hepatitis C virus infection.
AB  - Multiple factors may influence the host-virus interaction in patients infected
      with hepatitis C virus (HCV), and these may result in diverse disease
      presentations. In immune competent hosts, there is little evidence that direct
      cytopathicity plays a significant role in liver cell injury. However, when host
      conditions are altered to allow for unusually high levels of viral replication
      and viral protein expression (i.e., immunosuppression), HCV may induce direct
      hepatocellular damage. In most patients infected with HCV, a wide array of
      humoral and cell-mediated immune responses are triggered in response to HCV
      polypeptides; however, despite this host immune response, HCV infections usually
      persist. Furthermore, the host immune response, in its attempt to clear the virus
      from the liver, contributes to the hepatocellular damage (chronic hepatitis) seen
      in the majority of chronically infected patients.

PMID- 15560056
TI  - Histopathology of HCV infection.
AB  - The basic morphologic features of acute and chronic viral hepatitis C are similar
      to those of other hepatitides; however, hepatitis C is characterized by the
      histologic triad of lymphoid aggregates in portal tracts, epithelial damage of
      small bile ducts and microvesicular and macrovesicular steatosis of hepatocytes.
      Significant progress has been made in the demonstration of HCV in infected liver
      tissues by immunohistochemical and in situ hybridization techniques. The new
      classification of chronic hepatitis, based on etiology, grading (extent of
      necroinflammatory activity) and staging (extent of fibrosis) has been widely
      accepted and will lead to a better understanding of the variable course and
      response to therapy of this enigmatic disease.

PMID- 15560057
TI  - Use and interpretation of HCV diagnostic tests in the clinical setting.
AB  - The rapidly emerging and sometimes complicated field of HCV diagnostics can be
      simplified by classification of tests into two general categories: serologic
      tests which screen for anti-HCV antibodies, and molecular tests which are used to
      assess HCV viremia and characterize viral infection at the genetic level.
      Antibody tests include the highly sensitive screening enzyme immunoassays
      (current versions: EIA-2 and EIA-3), and supplemental tests such as the
      recombinant immunoblot assay (RIBA-2). Molecular assays such as HCV RNA
      polymerase chain reaction (PCR) may play an important role in confirming HCV
      infection in several clinical situations, such as immunosuppressed patients with
      chronic hepatitis C, patients with acute hepatitis who might be in the diagnostic
      "window" period prior to seroconversion, and seropositive patients with normal
      ALT values. Quantitative HCV-RNA tests, such as quantitative PCR (Q-PCR) and
      branched DNA (bDNA), provide valuable tools for assessing the level of HCV
      viremia prior to and during therapy. Genotype tests allow classification of HCV
      infection in one of six distinct HCV genotypes, although the clinical relevance
      of HCV genotype tests has not been established.

PMID- 15560058
TI  - The epidemiology of acute and chronic hepatitis C.
AB  - Although the incidence of newly acquired acute hepatitis C virus (HCV) infection
      has declined, an estimated 3.9 million Americans are chronically infected with
      HCV, most of whom are young adults who will be at risk of the severe consequences
      of their infection in the next 10 to 20 years. The relative importance of the two
      most common exposures associated with the transmission of HCV has changed over
      time. Blood transfusions, which account for a substantial proportion of HCV
      infections acquired more than 10 years ago, account for only a small portion of
      recently acquired infections. In contrast, injection drug use has accounted for a
      substantial portion of HCV infections during both the remote and recent past.
      Sexual exposures, which have been poorly ascertained particularly among patients
      with chronic hepatitis C, may account for 10% to 20% of HCV transmissions.
      Physicians and other health care professionals need to be educated not only about
      the appropriate medical management of HCV infected patients, but also about the
      known and potential risks for HCV infection, the need to ascertain complete risk
      behavior histories from their patients, the appropriate evaluation of high-risk
      patients for evidence of infections, and the recommendations for prevention.

PMID- 15560059
TI  - Clinical manifestations of hepatitis C.
AB  - Hepatitis C is a common cause of viral hepatitis that progresses to chronic
      infection in the majority of patients. Clinically, the infection is generally
      asymptomatic, but it may present with a wide variety of symptoms. Cirrhosis,
      hepatocellular carcinoma, cryoglobulinemia, auto-antibodies, and
      glomerulonephritis have been strongly associated with HCV. There is a probable
      association with autoimmune disease and NHL. More information is needed to
      determine whether lichen planus, PCT, and other disorders are part of the growing
      clinical spectrum or just coincidental associations with chronic liver disease.

PMID- 15560060
TI  - The natural history of chronic hepatitis C virus infection.
AB  - In conclusion, the natural history of chronic HCV infection has not yet been
      fully defined. Current data suggest that the process runs an indolent course
      during the first two decades after initial infection, accounting for modest
      morbidity and mortality. Serious sequelae are more likely to emerge as the
      disease process enters the third and fourth decades after infection. These
      sequelae will presumably be concentrated among those whose liver biopsies display
      features of cirrhosis, but seem less likely to effect those with liver biopsy
      evidence of chronic hepatitis alone unless their disease advances to cirrhosis.
      The frequency of progression from chronic hepatitis to cirrhosis as the disease
      process enters the third decade remains to be determined. Associated chronic
      alcoholism appears to be an important additive factor, but other factors that
      might promote disease progression need to be defined. It seems probable that end
      stage liver disease will result in only a proportion of infected individuals. If
      so, the challenge is to learn how to determine for each individual during the
      course of their chronic illness what outcome can be expected.

PMID- 15560061
TI  - Prevention of hepatitis C virus infection.
AB  - Despite the promising progress made in the development of experimental HCV
      hyperimmune globulin preparations and recombinant vaccines, prevention of HCV
      infection will continue to be an important research front for many years. Until
      effective and safe immunoprophylaxis is available, preventive efforts will
      require further understanding of risk factors associated with infection and
      implementation of strategies to reduce such exposures.

PMID- 15560062
TI  - Treatment of acute and chronic hepatitis C.
AB  - Interferon is currently the only available treatment for chronic hepatitis C but
      is effective in only about 40% of patients. Most of these responding patients
      relapse after short courses, so that sustained long-term viral-negative responses
      are uncommon (10% to 20%). However, longer treatment courses have significantly
      reduced relapse, thereby increasing sustained response rates. Furthermore, the
      combination of ribavirin with interferon shows promise for reducing relapse even
      further. The challenge for the future is to develop antiviral agents that will be
      effective in the large proportion of patients who do not respond to interferon.

PMID- 15560063
TI  - Clinical application of hepatitis C virus genotyping and quantitation.
AB  - Genotyping and quantitation of hepatitis C virus have provided great insights
      into the pathogenesis of chronic hepatitis C. The assays that are currently
      available for characterizing HCV remain powerful research tools that will be
      invaluable in future studies of the next generation of antiviral agents for the
      treatment of hepatitis C in much the same way that they have provided information
      about the effectiveness of interferon. Retrospective studies have demonstrated
      that HCV genotype and viral burden may play some role in disease progression and
      response to therapy. However, their utility in daily clinical practice in making
      decisions about treatment regimens or monitoring therapy in an individual patient
      remains difficult to define. As newer, more effective treatment strategies evolve
      (longer duration of treatment, combination therapy), previously identified
      predictors of disease severity or response to treatment may no longer be
      applicable.

PMID- 15560064
TI  - Treatment of HCV: approach to difficult cases.
AB  - The treatment of patients with HCV in itself represents a challenge for the
      treating physicians, but is particularly difficult in special situations where
      experience is limited. In patients with normal aminotransferases or an incomplete
      response to IFN, the safety of IFN administration is not the major issue, but one
      should consider the limited effectiveness of the therapy. In other patients, such
      as those with concomitant autoimmune hepatitis, an immunosuppressed state or a
      major psychiatric illness, IFN can be administered but may be associated with
      serious risks. In these cases, IFN should be used under strictly supervised
      circumstances and only by physicians with considerable familiarity with the drug.
      After needle stick exposures, IFN may prevent progression of acute infection to
      chronic hepatitis. Finally, in patients with well-established cirrhosis, IFN
      treatment may prevent decomposition or the development of hepatocellular
      carcinoma. In each of these categories, treatment must be tailored to the
      individual case based on good clinical judgment. It is hoped that greater
      experience, newer therapies, and a better understanding of the natural history of
      HCV infection will simplify the treatment of these cases that currently present
      difficult management problems.

PMID- 15560065
TI  - Hepatitis C infection in transplantation.
AB  - This review emphasizes the role of HCV in the transplant setting. Prolonged HCV
      infection results in end-stage liver disease and as such represents a common
      indication for liver transplantation. Recurrence of infection is almost universal
      after transplantation in those with viremia before transplantation. Acquired
      disease is uncommon but nevertheless important, particularly in organ populations
      in whom screening for infection is not routine. The natural history of post
      transplantation disease suggests that the effect on graft or patient survival is
      minor, at least during short-term follow-up. Long-term follow-up is needed, as
      well as more detailed study of the factors contributing to severity of post
      transplantation disease. Kidney transplant recipients are commonly infected with
      HCV prior to transplantation. HCV infection after transplantation is associated
      with an increased risk of liver disease and infectious complications, but its
      effect on survival is still controversial. Similarly, observations in recipients
      of other solid organ transplants, such as heart and lung, and bone marrow
      patients suggest that HCV infection usually is not a major cause of mortality in
      the first 5 to 10 years of follow-up. Many issues still need to be addressed. The
      most important is the identification of factors that contribute to disease
      progression. Finally, effective therapies to eradicate infection and prevent
      disease progression are awaited.

PMID- 15560066
TI  - Hepatitis C virus infection in pediatric patients.
AB  - In contrast to our understanding of hepatitis C virus infection in adults,
      relatively little is known about the evolution and treatment of HCV infection in
      pediatric patients. Children at risk for HCV infection include recipients of
      multiple blood-product transfusions, organ transplantation and infants born to
      HCV-infected mothers. A proportion of HCV-infected pediatric patients do not have
      an identifiable risk factor. HCV infection is commonly detected in children
      previously presumed to have non-A, non-B hepatitis and cryptogenic liver disease.
      HCV infection usually leads to mild chronic liver disease in children but is also
      associated with chronic active hepatitis and cirrhosis. Interferon therapy is
      effective in a proportion of patients with chronic hepatitis C.

PMID- 15560067
TI  - Alkylation and cleavage of a DNA fragment with trioligonucleotide reagent.
AB  - A possibility of site-directed chemical modification of a ssDNA fragment with
      "trioligonucleotide reagent" (TOR), consisting of a central oligonucleotide
      derivative carrying N-(2-chloroethyl)-N-(p-formylphenyl)-N-propyl-N-3-ydeneamino
      groups at both 5'- and 3'-thiophosphate ends and two border derivatives with 4
      carbohydrazidephenyl groups at their 3'- and 5'-phosphate ends, respectively, is
      shown. Products of site-directed fragment cleavage, more abundant than the
      alkylation products, were found at 50 degrees C. The overall level of DNA
      modification by TOR reached 30% at a small excess of the oligonucleotide
      derivatives.

PMID- 15560068
TI  - Oligonucleosome DNA fragmentation of caspase 3 deficient MCF-7 cells in palmitate
      induced apoptosis.
AB  - Oligonucleosomal fragmentation of nuclear DNA is the late stage hallmark of the
      apoptotic process. In mammalian apoptotic cells fragmentation is catalyzed by
      DFF40/ CAD DNase. DFF40/CAD primary activated through site-specific proteolytic
      cleavage by caspase 3. The absence of caspase 3 in MCF-7 leads to lack of
      oligonucleosomal DNA fragmentation under numerous apoptotic stimuli. In this
      study it was shown that palmitate induces apoptotic changes of nuclei and
      oligonucleosomal DNA fragmentation in casp3 deficient MCF-7. Activation and
      accumulation of 40-50 kDa DFF40 like DNases in nuclei and cytoplasm of palmitate
      treated MCF-7 were detected by SDS-DNA-PAGE assay. Microsomes of apoptotic MCF-7
      activate 40-50 kDa nucleases when incubated with human placental chromatin and
      induce oligonucleosomal fragmentation of chromatin in cell free system. Both
      DNases activation and chromatin fragmentation are suppressed in presence of
      caspase 3/7 inhibitor Ac-DEVD-CHO. Microsome associated caspase 7 is suggested to
      play the principal role in induction of oligonucleosomal DNA fragmentation of
      casp3 defitient MCF-7.

PMID- 15560069
TI  - Ribonucleic acids of human milk.
AB  - The milk feeding is the most essential process laying the foundation of human
      health at the postnatal development. However little is known about nucleic acids
      secreted into mother's milk during lactation. In order to investigate the
      composition and abundance of human milk NA we adapted the conventional isolation
      method to achieve high yield of total nucleic acids from milk samples.
      Concentration of total NA in milk samples of different donors varies from 20 to
      68 mkg/ml at early stages of lactation. The average concentration tends to fall
      down to the end of lactation. The chain length of the major forms of NA varies
      from mononucleotides up to approximately 100 bases. Compositions of milk
      oligonucleotides are similar in samples of different donors. Major milk
      oligonucleotides are formed of RNA. Human milk contains the set of long-chain
      oligonucleotides with a developed secondary structure. Sequences of some oligo
      RNAs correspond to the 3'-part of 5.8 S human ribosomal RNA and to the 3'-parts
      of tRNAVal and tRNATyr Primary structures of some others oligo-RNAs were related
      to fragments of human 18S and 28S rRNAs.

PMID- 15560070
TI  - Expression of the MDR1 and MRP genes in patients with lymphoma with primary bone
      marrow involvement.
AB  - Expression of MDR1 and MRP genes in patients with low-grade and high-grade non
      Hodgkin's lymphomas with primary bone marrow involvement before and after
      chemotherapy was investigated. The data demonstrate that overexpression of MDR1
      and MRP genes in hematological malignancies elevates in patients after
      chemotherapy and correlates with poor clinic prognosis and more frequent
      recurrences of the malignancies.

PMID- 15560071
TI  - Oxidative DNA cleavage by free and oligonucleotide-conjugated O-bromobenzoic acid
      in the presence of copper(II) ions.
AB  - o-Bromobenzoic acid was found to promote copper-dependent reactive oxygen species
      formation from molecular oxygen, resulting in DNA base modification and backbone
      cleavage. The oligonucleotide conjugate bearing 5-(4'-aminopropyl-sulfomoyl)-2
      bromobenzoic acid as a reactive group was synthesized and DNA cleavage activity
      of this oligonucleotide conjugate was tested on a model deoxyoligonucleotide.

PMID- 15560072
TI  - Investigation of tumor-derived extracellular DNA in blood of cancer patients by
      methylation-specific PCR.
AB  - The frequency of APC, RASSF1A, RARbeta, CDH1 and CDH13 gene promoter methylation
      in samples of DNA isolated from breast and lung patient plasma was studied in
      order to develop the noninvasive tumor-specific DNA detection method. Methylation
      of at least one of genes was detected in extracellular DNA from most of the
      cancer blood specimens. The results obtained indicate that promoter
      hypermethylation of a number of marker genes represents a promising serum marker
      for early breast and lung cancer detection.

PMID- 15560073
TI  - Silencing of MDR 1 gene in cancer cells by siRNA.
AB  - Inhibition of p-glycoprotein (PGP) expression and reverse of multidrug resistance
      (MDR) phenotype in KB-8-5 cells by synthetic 21-bp double-stranded
      oligoribonucleotides were investigated. siRNA constructs for the efficient down
      regulation of MDR1 that are active in nanomolar concentrations and cause reversal
      of MDR phenotype in cells were developed.

PMID- 15560074
TI  - Silencing of c-myc expression in tumor cells by siRNA.
AB  - Suppression of c-myc protooncogene expression in KB-3-1 cells by siRNA was
      investigated. The siRNA duplex targeted to the exon 3 of c-myc mRNA was prepared
      by in vitro transcription with T7 RNA polymerase on short dsDNA-templates. It was
      found that incubation of KB-3-1 cells in the presence of 75 nM siRNA results in
      decrease of the c-myc mRNA level down to 5% of the level in the control cells and
      significant decline of KB-3-1 cell proliferation rate. Using 200 nM siRNA four
      fold decrease of KB-3-1 cells proliferation rate was observed and this effect was
      stable at least 96 h after transfection.

PMID- 15560075
TI  - Simple and rapid procedure suitable for quantitative isolation of low and high
      molecular weight extracellular nucleic acids.
AB  - The procedure based on binding of nucleic acids with glass surface in presence of
      chaotropic salts was adapted for efficient isolation of 100-10000 b.p. DNA
      fragments and 50-10,000 b. RNA fragments. The method provide 90% and 85% efficacy
      of isolation of 100 b.p. DNA and 100 b. RNA fragments respectively. High
      molecular weight nucleic acids are isolated with 98% efficacy. Isolated nucleic
      acids are free from contaminations, influencing nucleic acids modifying enzymes
      and fluorochromes. The method is rapid, simple and cost-effective.

PMID- 15560076
TI  - Extracellular circulating nucleic acids in human plasma in health and disease.
AB  - The concentration of extracellular DNA and RNA in blood plasma of healthy donors,
      trauma patients, patients with breast and lung cancer, nonmalignant breast tumors
      and nonmalignant lung diseases were estimated. Significant amounts of
      extracellular RNA were found in plasma of trauma patients. The concentration of
      DNA and RNA in plasma of trauma patients correlates with the extent of
      posttraumatic organ failure. Extracellular RNA was not found in the plasma of
      breast cancer patients and patients with nonmalignant breast tumors, whereas a
      very high concentration of extracellular RNA was found in patients with malignant
      and nonmalignant diseases of lung.

PMID- 15560077
TI  - Ribonuclease activity of the peptides with alternating arginine and leucine
      residues conjugated to tetrathymidilate.
AB  - RNA cleaving conjugates have been prepared by attachment of
      oligodeoxyribonucleotide TTTT to peptides containing arginine, leucine, proline
      and serine residues. The highest activity was displayed by the conjugates
      containing peptides with alternating arginine and leucine residues (LR)4G-amide.
      Ribonuclease activity of the conjugates pep-T4 decreases in the order T4-(LR)4G >
      T4-(LR)2G > T4-(LLRR)2G > T4-(LR)2PRLRG > S2R3-Hmda-T4 > or = R5 double dagger
      (LR)3. According to CD spectra, the free peptide (LR)4G-amide in water solution
      at neutral pH and physiological ionic strength has no pronounced secondary
      structure whereas conjugated to oligonucleotide it acquires a folding similar to
      alpha-helix.

PMID- 15560078
TI  - In vitro selection of single-stranded DNA aptamers that bind human pro-urokinase.
AB  - Single-chain pro-urokinase is an inactive proenzyme form of human urokinase
      (urinary plasminogen activator) with a Mr of 50,000 which is converted to the
      active two-chain form by catalytic amounts of plasmin. It is used for
      thrombolytic therapy of acute myocardial infarction and acute ischemic stroke. We
      have isolated single-stranded DNA molecules with significantly increased binding
      affinity for human pro-urokinase by SELEX (systematic evolution of ligands by
      exponential enrichment) procedure from a pool of 10(15) molecules containing 24
      randomized positions which are flanked by defined regions. ssDNA from this
      library was hybridized with helper "fixture", thus allowing the central random
      chain to fold into complex three-dimentional shapes. Sequencing data from pro
      urokinase aptamers obtained after 12 selection cycles displayed a highly
      conserved 12-14 base region.

PMID- 15560079
TI  - Hybridization of antisense oligonucleotides with alpha-sarcin loop region of
      Escherichia coli 23S rRNA.
AB  - Binding of complementary oligonucleotides (ONs) with alpha-sarcin loop region
      (2638-2682) of Escherichia coli 23S rRNA was investigated. Four of the tested
      pentadecanucleotides efficiently bound to target sequences with association rate
      and equilibrium constants approximately 10(3) M(-1)s(-1) and 10(7) M(-1),
      respectively. ON S5 (CGAGAGGACCGGAGU) complementary to the sequence 2658-2672
      displayed the highest affinity to the target. Activation energy for binding of ON
      S5 was measured to be 11 kcal/mol; this value corresponds to approximately 10% of
      the calculated enthalpy of the local RNA structure unfolding in the presence of
      this oligonucleotide. The activation energy value is evidence for the
      heteroduplex formation to occur via strand displacement pathway; the initiation
      of heteroduplex formation requires disruption of 1-2 base pairs in RNA hairpin.

PMID- 15560080
TI  - The role of hydrophobic interactions in catalysis of RNA cleavage by 1,4
      diazabicyclo[2.2.2]-octane based artificial ribonucleases.
AB  - Molecular interactions of RNA cleaving compounds-conjugates of 1,4
      diazabicyclo[2.2.2.]octane substituted at the bridge position with
      tetradecamethylene fragment and imidazole were investigated using light
      scattering and small angle x-ray scattering methods. The compounds are known to
      efficiently cleave RNA and one source of the activity could result from micellar
      catalysis. It was found that the compounds indeed are capable of forming complex
      aggregates in solution. However, maximal efficacy of RNA cleavage by the
      conjugates is observed at concentrations well below the concentration required
      for micelle formation.

PMID- 15560081
TI  - Molecular design of artificial ribonucleases using electrostatic interaction.
AB  - A number of small organic ribonucleases have been synthesized with rigid
      polycationic structures containing an aromatic framework with two residues of bis
      quaternary salts of 1,4-diazabicyclo[2.2.2]octane (DABCO) bearing various
      substituents. The compounds carrying positively charged groups connected via
      rigid linker are expected to bend the sugar-phosphate backbone and can stimulate
      the intramolecular phosphoester transfer reaction.

PMID- 15560082
TI  - Photoanalogues of the initiation substrates of the RNA polymerase II, 5-azido-2
      nitrobenzoyl derivatives of the ATP gamma-amidophosphate: the possible
      photoinduced degradation of the functional group to an N-arylhydroxylamine.
AB  - Photoanlogues of the initiation substrates of the RNA polymerase II,
      N3ArNH(CH2)(n)NHpppA where N3Ar is 5-azido-2-nitrobenzoyl group (n = 2 or 4) were
      synthesized, allowing the preparation of photoreactive oligonucleotides in situ
      by RNA polymerase II for application as photolabels. Photolysis of p-nitro
      substituted aromatic azide in aqueous medium was investigated. Using the azoxy
      coupling reaction it was possible to determine whether a nitrene or p-nitrophenyl
      hydroxylamine azoxy compound is the trappable intermediate that is generated at
      ambient temperature in aqueous solution.

PMID- 15560083
TI  - Release of nucleic acids by eukaryotic cells in tissue culture.
AB  - Extracellular nucleic acids in cultures of A431 and HeLa cells were investigated.
      The data obtained demonstrate the presence of high weight DNA and RNA in the
      extracellular medium. Temporal changes of extracellular nucleic acids levels in
      growth medium were investigated.

PMID- 15560084
TI  - Preparation of DNA chips using polyamine-oligonucleotide conjugates.
AB  - A convenient and efficient method for three-dimensional immobilizing
      oligonucleotides on glass was developed using oligonucleotide derivatives bearing
      a polyamine linker (PA-oligo conjugates). Polyamine (polylysine, poly(lysine,
      phenylalanine), polyethyleneimine) residues stipulate durable fixation of such
      conjugates to the glass surface with a high yield (90-95%). A DNA fragment (414
      mer) is hybridized specifically to an immobilized oligonucleotide.

PMID- 15560085
TI  - Properties of antigenomic hepatitis delta virus ribozyme cis- and trans- analogs.
AB  - A series of permuted variants of antigenomic HDV ribozyme and trans-acting
      variants were constructed. The catalytic activity study of the ribozymes has
      shown that all the variants were capable of self-cleaving with equally biphasic
      kinetics. Ribonuclease and Fe(II)-EDTA cleavage have provided evidence that all
      designed ribozymes fold according to the pseudoknot model and the conformations
      of the initial and cleaved ribozyme are different. A scheme of HDV ribozyme self
      cleavage reaction was suggested. The role of hydrogen bonds in the reaction was
      evaluated by substitution of ribose in the ribozyme for deoxyribose. It was found
      that the 2'-OH group of U23 and C27 is critical for the reaction to occur; the 2'
      OH group of U32 and U39 is important, while 2'-OH groups of other nucleotides of
      loop 3, stem 4 and stem 1 are unimportant for the cleavage activity.

PMID- 15560086
TI  - Binding features of BCL2-targeted oligodeoxynucleotides with K562 cells.
AB  - Delivery of various oligodeoxynucleotides into cells is mediated by binding to
      certain surface proteins followed by receptor-mediated endocytosis. Moreover,
      oligonucleotides are able to provoke perturbation of cell surface proteins and
      growth factor receptors among them. Here we described binding sense BCL2
      oligodeoxynucleotide targeted to translation start of BCL2 mRNA (ODN) with K562
      cells. At low concentration ODN bound efficiently with K562 and penetrated into
      the cells via binding cell surface with rather high affinity and priming new
      binding sites. The loose binding constant at 4 degrees C was 1.8 x 10(9) M(-1)
      both for binding ODN in solution and ODN-associated liposome. The number of loose
      binding sites under both treatments was rather high: 4.6 to 6.6 pmoles per 10(6)
      cells. The extent of ODN penetration into the cells showed higher potential site
      numbers than initially seen and reached 8.6 pmoles per 10(6) cells for four hours
      incubation at 37 degrees C.

PMID- 15560087
TI  - Oligonucleotide--minor groove binder 1:2 conjugates: side by side parallel minor
      groove binder motif in stabilization of DNA duplex.
AB  - Synthetic polycarboxamides consisting of N-methylpyrrole (Py), N-methylimidazole
      (Im), N-methyl-3-hydroxypyrrole (Hp) and beta-alanine (beta) show strong and
      sequence-specific interaction with the DNA minor groove when they form hairpin
      structures with side-by-side antiparallel motifs. In the present paper, new
      conjugates containing two ligands linked to the same terminal phosphate of DNA
      strand were constructed. The paper describes optimized synthesis and properties
      of oligonucleotide-linked polyamide strands that insert into the minor groove of
      a duplex in a parallel or antiparallel orientation. Strong stabilization of DNA
      duplexes by two attached minor groove ligands is demonstrated by the thermal
      denaturation method. The unmodified duplex 5'-CGTTTATTp-3'/5'-AATAAACG-3' melts
      at 20 degrees C. When one tetra(Py) residue was attached to the first strand of
      this duplex, denaturation temperature was increased to 46 degrees C; attachment
      of the second tetra(Py) in a parallel orientation resulted in denaturation
      temperature of 60 degrees C. It is even higher than in case of "classic"
      octapyrrole hairpin ligand (Tm = 58 degrees C). Sequence-specific character of
      stabilization by two conjugated ligands was demonstrated for G:C-containing
      oligonucleotides attached to tetracarboxamide and octacarboxamide ligands
      constructed from Py, Im and beta units according to established recognition rules
      (deltaTm = 20 degrees C). The two-strand parallel minor groove binder
      constructions attached to addressing oligonucleotides could be considered as site
      specific ligands recognizing single- and double-stranded DNA similarly to already
      described hairpin MGB structures with antiparallel orientation of carboxamide
      units.

PMID- 15560088
TI  - New photoreactive oligoribonucleotide conjugates: hybridization and modification
      assays.
AB  - An evaluation of hybridization and modification abilities of new types of
      photoactivatable oligoribonucleotide conjugates bearing p
      azidotetrafluorobenzamide group at the N4 of cytosine is presented.

PMID- 15560089
TI  - Ribonuclease activity of cationic structures conjugated to lipophilic groups.
AB  - Cationic compounds containing benzene ring substituted with the bis-quaternary
      salt of diazabicyclo[2.2.2]octane (DABCO) bearing a polymethylene fragment at the
      bridge positions display ribonuclease activity. Efficacy of the catalysis is
      affected by geometry of the cationic structures and the size of the attached
      aliphatic fragment. The cleavage occurs primarily within CA sequences. The
      compounds do not possess tradition groups participating in the
      transesterification step of RNA cleavage reaction, therefore a speculative
      mechanism of cleavage could be inducing a conformational stress on the RNA sugar
      phosphate backbone providing fragility to phosphodiester bonds.

PMID- 15560090
TI  - Thermodynamics of interaction of phthalocyanine-oligonucleotide conjugates with
      single- and double-stranded DNA.
AB  - Thermodynamics of interaction of phthalocyanine-oligonucleotide conjugates with
      single- and double-stranded DNA resulting in formation of duplexes and triplexes
      was measured by UV melting method. It was shown that a phthalocyanine moiety of
      conjugates stabilized the formation of duplexes and triplexes.

PMID- 15560091
TI  - Toward the development of metal-free synthetic nucleases: cleavage of a model
      substrates by 1,4-diazabicyclo[2.2.2]octane derivatives.
AB  - Artificial ribonucleases of A(n)BCL series were synthesized by solid-phase
      method. They consist of a hydrophobic alkyl radical A (n = 3-12 carbon atoms), an
      "RNA-binding domain" B (bisquaternary salt of 1,4-diazabicyclo[2.2.2]octane), a
      "catalytic domain" C (histidine residue) and a "linker" L that joins the domains
      B and C. The effect of the alkyl radical on the catalytic properties of the
      chemical catalyst was studied using three activated phosphate ester substrates: p
      nitrophenyl phosphate, bis-p-nitrophenyl phosphate, and thymidine-3'-p
      nitrophenyl phosphate.

PMID- 15560092
TI  - Synthesis of monomers bearing at the 2'-position cyanomethoxycarbonyl group for
      phosphoramidite oligonucleotide synthesis.
AB  - A novel series of phosphoroamidites for the synthesis of 2-modified
      oligonucleotides was designed and synthesized on the base of 2'-amino uridine and
      2'-amino arabinoadenosine. The amino groups in these compounds were acidified by
      bis-cyanomethyl esters of different dicarbonic acids. Generated reactive linker
      groups containing cyanomethoxycarbonyl groups are stable under conditions of
      oligonucleotide synthesis but could be easily functionalised in post-synthetic
      stage by treatment with compounds bearing primary amino groups.

PMID- 15560093
TI  - Assay of random RNA oligomerisation in buffers with high concentrations of
      divalent metal ions.
AB  - Certain conditions, such as high concentrations of divalent metal ions in the
      reaction buffer or low pH, can cause aggregation and precipitation of RNA species
      with complementary sequences. If oligomerisation has gone unnoticed, some
      sequences from the pool of random RNA may be underrepresented or even lost at the
      very beginning of the selection experiment. Two simple assays for RNA
      oligomerisation are suggested. One is based on electrophoresis in non-denaturing
      gels, and the other uses gel-filtration.

PMID- 15560094
TI  - Characteristics of lipids imbalance in patients with tick-borne encephalitis.
AB  - Using a novel approach, we have analyzed 30 parameters characterizing detailed
      spectrum and fractional content of LPs in plasma of patients with tick-borne
      encephalitis (TBE). The blood plasma of all TBE patients (30 patients), as
      compared with that of healthy individuals (120 patients), is characterized by
      decreased concentrations of many LP subfractions and of the total concentration
      of all plasma LPs (hypolipoproteinemia). The observed difference in some
      parameters was statistically significant. Using computer-assisted factor
      analysis, we have shown that according to these 30 parameters TBE patients are
      similar to patients with multiple sclerosis and systemic lupus erythematosus. The
      results provide grounds for using data on blood plasma LPs as additional criteria
      for diagnosis of TBE.

PMID- 15560095
TI  - Strong changes in lipoproteins and autoantibodies of blood serum of the Tundra
      Nency population as a result of environmental radiation on the territory they
      inhabit.
AB  - As a result of large-scale nuclear tests on the Novaya Zemlya test site (1955-62)
      the Tundra Nentsy population of Yamal-Nentsy autonomous region (YNAR) fell under
      the constant influence of incorporated radioactive isotopes (137Cs and 90Sr).
      Therefore, it is very important to analyze a possible spectrum of diseases of
      Tundra Nentsy population.

PMID- 15560096
TI  - Binding properties of the conjugates of oligo(2'-O-methylribonucleotides) with
      minor groove binders targeted to double stranded DNA.
AB  - Design, synthesis, physico-chemical and in vitro biological studies of new
      pyrimidine oligo(2'-O-methylribonucleotide) conjugates with oligocarboxamide
      minor groove binders (MGB) and benzoindoloquinoline intercalator (BIQ) are
      described. These conjugates formed stable triple helices with the target double
      stranded DNA and inhibited its in vitro transcription upon binding.

PMID- 15560097
TI  - A new approach to revealing point mutations in DNA analyzed by colorimetric
      detection.
AB  - A new approach to detection of point mutations in an amplified DNA was developed.
      The approach is based on highly selective ligation (T4 DNA ligase) of a tandem of
      short oligonucleotides one of which contains the biotin group. The ligation
      product is formed only when the hybridization complex DNA/tandem is formed and
      the tandem is perfect. The hybridization complex DNA/(biotinylated ligation
      product) was separated from the biotinylated component of the tandem by UV
      immobilization of the reaction mixture on a nylon membrane. The immobilized
      hybridization complex was detected colorimetrically by a streptavidin-alkaline
      phosphatase cojugate with a chromogenic substrate.

PMID- 15560098
TI  - Two-component 10-23 DNA enzymes.
AB  - A new strategy for engineering of catalytic two-component constructions based on
      10-23 DNAzyme was proposed. The using of a combination of shortened DNAzyme with
      2'-O-methyl oligomers as effectors significantly increased the catalytic activity
      of this DNAzyme.

PMID- 15560099
TI  - Binary hammerhead ribozymes with high cleavage activity.
AB  - Binary hammerhead ribozymes consisted of two oligoribonucleotides capable of
      assembling into hammerhead structure (without loop II) on the RNA target were
      engineered. Catalytic activities of such ribozymes were investigated in
      comparison with their full-length analog and ribozyme where two strands were
      jointed by non-nucleotidic linker. Binary constructs were shown to be
      significantly more active than the parent full-length hammerhead ribozyme.

PMID- 15560100
TI  - Lactoferrin interacts with nucleotides.
AB  - Lactoferrin (LF) is an iron-binding glycoprotein found predominantly in milk and
      in granulocytes. LF is extremely polyfunctional protein some biological functions
      of which are determined by its capacity to bind iron, but many other functions
      are iron-independent. In this article we show for the first time that LF
      interacts with a number of various mononucleotides.

PMID- 15560101
TI  - Efficient cleavage of DS DNA by bleomycin conjugated via hexaethylene glycol
      linker to triplex-forming oligonucleotides.
AB  - New conjugates of bleomycin A5 with oligonucleotides are synthesized. The
      bleomycin residue was attached to the 3'- or 5'- terminus of hexadecathymidilate
      via a hexaethylene glycol phosphate linker. Newly designed conjugates were shown
      to cleave site-specifically both strands of a dsDNA fragment within a triplex.
      The maximum extent of cleavage for individual strand amounts to 61%.

PMID- 15560102
TI  - Comparison of enzymatic properties of DNA-abzymes and human DNAses.
AB  - DNA-hydrolyzing antibodies (DNA-abzymes, Abz) were shown to be good biochemical
      markers of some autoimmune diseases such as systemic lupus erythematosus (SLE)
      and multiple sclerosis (MS). To better understand mechanisms of abzyme
      generation, one needs to know optimal conditions for DNA hydrolysis by DNA
      abzymes, as well as their enzymatic properties in comparison with those of
      enzymes possessing the same activity. In contrast to human urine
      deoxyribonucleases, DNA-hydrolyzing antibodies efficiently digested both single-
      and double-strand DNA. It was shown that polyclonal antibodies (Abs) in MS may
      contain up to several types of DNase activities, either activated by metal ions
      or not.

PMID- 15560103
TI  - The influence of nearest neighbours on the efficiency of coaxial stacking at
      contiguous stacking hybridization of oligodeoxyribonucleotides.
AB  - Contiguous stacking hybridization of oligodeoxyribonucleotides with a stem of
      preformed minihairpin structure of a DNA template was studied with the use of UV
      melting technique. It was shown that the free-energy of the coaxial stacking
      interaction (deltaG degrees ST at 37 degrees C, 1 M NaCl, pH 7.4) at the
      complementary interface XA*pTY/ZATV (an asterisk stands for a nick) strongly
      depends on the type of nearest neighbor bases X and Y flanking the nicked
      dinucleotide step. The maximum efficiency of the coaxial stacking was observed
      for the PuA*pTPy/PuATPy interface, whereas the minimum efficiency was obtained
      for the PyA*pTPu/PyATPu interface. A 5'-phosphate residue in the nick enhances
      the coaxial stacking. In dependence on duplex structure the observed efficiency
      of A*T/AT coaxial stacking varied from (- 0.97 kcal/mol) for unphosphorylated
      TA*TA/TATA interface to three-fold higher value (- 2.78 kcal/mol) for GA*pTT/AATC
      interface.

PMID- 15560104
TI  - The influence of the non-nucleotide insert on the hybridization properties of
      oligonucleotides.
AB  - The effect of different non-nucleotide inserts incorporated into oligonucleotide
      chains on their hybridization properties was studied by the method of thermal
      denaturation. Various types of alkyldiols and oligoethylene glycols were used as
      inserts modifying oligonucleotide backbone. Such modification of oligonucleotides
      caused the destabilization of their complementary complexes. It was shown that
      the hybridization properties of the modified oligonucleotides depend on several
      features of inserts: the type, number, length of insertions, and positions of
      interrupted dinucleotide steps in oligonucleotide chain.

PMID- 15560105
TI  - The lymphatic vascular system: secondary or primary?
AB  - It has generally been accepted that the blood vascular system is primary and the
      lymphatic vascular system secondary. Diseases of the blood vascular system are
      the leading cause for mortality and morbidity in developed nations. In contrast,
      lymphedema is seldom life-threatening and can generally be well-managed by
      combined physiotherapy. During ontogeny, the blood vessels and the heart develop
      much earlier than the lymphatic vessels. However, there is growing evidence that
      the first vascular system occurring during ontogeny and phylogeny has lymphatic
      functions. Defense mechanisms are crucial for all organisms irrespective of their
      size. Macrophages precede the emergence of erythrocytes during ontogeny, and
      their circulation in the hemolymphatic (more accurately, lymphohematic) system of
      insects, which do not possess erythrocytes, shows that the lymphatic function is
      primary whereas the nutritive function is secondary, needed only in larger
      organisms. In molluscs and arthropods, which have an open vascular system,
      hemocyanin has both oxygen transporting and defense functions. In vertebrates,
      the early blood vessels have structural characteristics of lymphatics and express
      the lymphendothelial receptor flt-4 (Vascular Endothelial Growth Factor Receptor
      3). Later, flt-4 becomes restricted to the definitive lymphatics, which are
      either formed from the primary vessels or from mesodermal lymphangioblasts. The
      primary lymphatic function has become overruled by the nutritive function in
      blood vessels of larger animals. The circular movement of cells is driven by a
      blood heart, which, however, is not an unique organ. Lymph hearts are present in
      lower vertebrates, still develop transiently in birds, and are vestigial in the
      contractile lymphangion which "circulates" immune cells. We conclude that the
      definitive lymphatics are perhaps secondary in mammals, but the blood vascular
      system seems to develop on the basis of an ancestral lymphatic system with lymph
      hearts.

PMID- 15560106
TI  - Early postnatal growth of the initial lymphatics in the ventral stripe of
      spinotrapezius muscle of the rat.
AB  - The aim of this study was the morphological description of the early postnatal
      growth of initial lymphatics in the ventral stripe of the spinotrapezius muscle
      of the rat. Electron-microscopically it was found that in the muscles of newborn
      rats no well-developed lymphatics were apparent, but the presence of specifically
      polarized mesenchymal cells in the close vicinity of central blood vessels was
      evident. In animals aged one-day through two-weeks-old, those modified
      mesenchymal cells continuously joined with one another, to form simple
      intercellular contacts and incomplete lymphatic lumina. Morphologically, they
      were well demarcated relative to the surrounding muscular interstitium. In three
      week-old rats, all intramuscular lymphatics were well developed, including fine
      intraluminal valves, and their endothelial cells presented slight pinocytotic
      activity and a complete absence of a basal lamina. In growing lymphatic
      endothelial cells, no mitoses or signs of sprouting, typical for the growth of
      blood capillaries, were found. In conclusion, a possible morphological mechanism
      enabling the expansion of the growing lymphatic endothelial cells could be the
      specific remodeling of cytoplasmic vacuoles accumulated in the peripheral
      cellular processes.

PMID- 15560107
TI  - The pattern of fibrillin deposition correlates with microfibril-associated
      glycoprotein 1 (MAGP-1) expression in cultured blood and lymphatic endothelial
      cells.
AB  - Fibrillins constitute the major structural components of 10-12nm microfibrils of
      the extracellular matrix of several elastic and non elastic tissues and of
      initial lymphatic vessel anchoring filaments. Microfibril-Associated Glycoprotein
      1 (MAGP-1) binds fibrillin to tropoelastin during elastogenesis. We recently
      reported that cultured blood endothelial cells deposit fibrillin in a honeycomb
      pattern, whereas lymphatic endothelial cells form an irregular web. The aim of
      this immunohistochemical study was to verify whether the deposition pattern of
      fibrillin is related to the expression of MAGP-1 in confluent and postconfluent
      cultures of bovine aortic (AEC), pulmonary artery (PAEC) and lymphatic
      endothelial cells (LEC). In AEC and PAEC, MAGP-1 and fibrillin co-localized and
      their deposition increased with time in culture. In AEC, both proteins formed a
      honeycomb pattern. In LEC, MAGP-1 deposition was still negligible when fibrillin
      formed an irregular web covering the entire surface. PAEC, which in vivo are
      exposed to physiological conditions intermediate between AEC and LEC, had an
      intermediate pattern of deposition of fibrillin and MAGP-1. Assuming that early
      elastogenesis is an intrinsic functional need for the aorta, but not for the
      thoracic duct, we propose that delayed appearance of MAGP-1 in LEC may correlate
      with their irregular fibrillin deposition. Different fibrillin scaffolds could in
      turn account for the specificity of elastic fibers in compliance with the
      specific functional requirements of the tissue.

PMID- 15560108
TI  - Validity and intra- and interobserver reliability of an indirect volume
      measurements in patients with upper extremity lymphedema.
AB  - We investigated a method of indirect volume measurement that utilized surface
      measurements and a simplified formula derived from the formula for a frustum
      (Sitzia's method) to determine limb volumes in patients with breast cancer
      related lymphedema of the upper extremity. Repeated measurements of upper
      extremity limb volume were obtained by two observers on both upper extremities of
      30 women with unilateral lymphedema. Volume was calculated using a simplified
      formula and compared with water displacement method as a gold standard. Indirect
      volume determination using Sitzia's method is comparable with the water
      displacement method, has comparable intra- and interobserver reliabilities, and
      can be used for diagnosis and follow up measurements of lymphedema. Indirect
      volume determination using surface measurements at 8 cm intervals is only
      suitable for follow up measurements. The methods should not be used
      interchangeably.

PMID- 15560109
TI  - The effect of diaphragmatic peritoneal lymphatics on peritoneal adhesions: an
      experimental study.
AB  - In this study, we examined the effect of diaphragmatic peritoneal lymphatic
      function on the formation of peritoneal adhesions. A two phased design was used
      in fifty-two Wistar albino female rats. In the first phase (n = 12), the effects
      of diaphragmatic peritoneum damage model on the cecum and the terminal ileum were
      evaluated. In the second phase, the rats (n = 40) were divided into two equal
      groups. The adhesion model was created only in the cecum and the terminal ileum
      in the first group, whereas the diaphragmatic peritoneal damage model was created
      in the second group together with the same adhesion model. The rats were
      sacrificed on day 10 postoperatively and the adhesions formed were graded. In the
      first group, adhesions were formed at grade 1 in 5 rats (25%), grade 2 in 11 rats
      (55%) and grade 3 in 4 rats (20%), whereas adhesions were formed at grade 1 in 2
      rats (10%), grade 2 in 8 rats (40%) and grade 3 in 10 rats (50%) in the second
      group (X2: 21.65, p < 0.0001). Diaphragmatic peritoneal lymphatic function
      reduced the number of adhesions and severity of the adhesions which occurred
      among intraabdominal organs after laparotomy. These findings suggest that special
      care should be undertaken to avoid damaging the diaphragmatic peritoneum during
      abdominal surgery so as to reduce the incidence of peritoneal adhesions.

PMID- 15560110
TI  - Lymphatic aneurysm of the heart.
AB  - The Annular Subvalvular Left Ventricular Aneurysm (ASLVA) is a rare entity, which
      occurs usually in young ethnic groups from Sub-Saharan Africa and South India.
      These aneurysms are situated immediately beneath the mitral and aortic valves and
      extend around in the substance of fibrous ring, from which valves arise. Their
      etiology is still obscure. Fifteen consecutive cases of ASLVA were treated
      surgically for this heart condition. Their clinical presentations, surgery,
      histopathology of aneurysmal wall were studied. Infective diseases with
      associated mediastinal lymphadenopathy were observed in all patients prior to the
      time the diagnosis of ASLVA was made. Nine patients had also lymphadenopathy in
      another region. Sinus of Valsalva Aneurysm was an associated finding in three
      patients. Dense fibrous tissue was the most common histopathological feature of
      the aneurysmal wall. Endothelium within the structure of the aneurysmal wall,
      "compressed" myocardium around the ASLVA wall, dilated and deformed heart
      lymphatics with lymph extravasation, and lymphatic neovascularization were all
      found in some histopathology specimens. Post-inflammatory destruction of
      mediastinal lymph nodes may obstruct lymph outflow from the heart, cause
      backwards lymphostasis, damage lymphatic vessels in the heart, and can lead to
      aneurysm formation. Increased intravascular shear stress triggers release of
      endothelial growth factors (bFGF, TGF-beta) and leads to neovascularization and
      tissue fibrosis, the most common feature of aneurysmal wall.

PMID- 15560111
TI  - Lymphatic filariasis and the International Society of Lymphology.

PMID- 15560112
TI  - Electron microscope immunocytochemical localization of cyclooxygenase-1 and -2 in
      pseudopregnant rat corpus luteum during luteolysis.
AB  - Prostaglandins converted from arachidonic acid by cyclooxygenases play an
      important regulatory role in regression of the corpus luteum. To reveal luteal
      distribution of cyclooxygenase isoforms during luteolysis, an electron microscope
      immunocytochemical study was performed. Cyclooxygenase-1 and -2 were found both
      in luteal steroid-producing and interstitial cells on days 13, 15 and 18 of the
      adult pseudopregnant rat. Cyclooxygenase-2 immunolabelling was predominantly seen
      in non-luteal cells. The two enzymes were localized in similar fashion to the
      plasma membrane, rough and smooth endoplasmic reticulum, lipid bodies and
      mitochondria, but differently in the nuclear compartment. Cyclooxygenase-1
      labelling was found only in the perinuclear region, while cyclooxygenase-2 was
      localized to the nuclear envelope, region of condensed heterochromatin as well as
      at the perimeter of the heterochromatin. Nuclear residence may indicate
      additional roles for cyclooxygenase-2 in regulating gene expression.
      Identification of both enzymes on lipid bodies suggests that these inclusions may
      be involved in luteal prostanoid production.

PMID- 15560113
TI  - 15-deoxy-delta12,14-prostaglandin-J2 inhibits expression of eNOS in human
      endothelial cells.
AB  - 15-Deoxy-delta12,14-Prostaglandin-J2 (15d-PGJ2), an endogenous ligand of
      PPARgamma transcription factor, modifies expression of many genes involved in
      inflammation and angiogenesis. Enzyme which contributes to regulation of both
      these processes is endothelial nitric oxide synthase (eNOS). Our aim was to
      investigated the effect of 15d-PGJ2 on eNOS in human umbilical vein endothelial
      cells (HUVEC). We demonstrated that 24 h incubation of HUVEC with 15d-PGJ2 (1-10
      microM) does not influence eNOS. On the contrary, the longer exposure (48-72 h)
      resulted in concentration-dependent inhibition of eNOS mRNA and protein
      expressions and led to reduction in eNOS enzymatic activity by approximately 50%.
      This effect was mediated by regulation of the transcription rate from eNOS
      promoter, what may be associated with inhibition of AP-1 binding capacity. The
      stability of mRNA was unchanged. Since none of the observed effects could be
      mimicked by troglitazone, a more potent PPARgamma ligand, we suppose that 15d
      PGJ2 diminishes expression of eNOS via PPARgamma-independent mechanisms.

PMID- 15560114
TI  - Nociception and the differential expression of cyclooxygenase-1 (COX-1), the COX
      1 variant retaining intron-1 (COX-1v), and COX-2 in mouse dorsal root ganglia
      (DRG).
AB  - Prostaglandins (PGs) formed via the cyclooxygenase (COX) pathway mediate
      hyperalgesia in sensory nerve endings. To investigate the role of the COX
      isoforms in pain transmission we recently studied nociception in COX-isozyme
      deficient mice using models of "sharp" rapidly transmitted pain (hot-plate) and
      slowly developing, diffuse pain (writhing) [Ballou L, Botting RM, Goorha S, Zhang
      J, Vane JR. Nociception in cyclooxygenase isozyme-deficient mice. Proc Natl Acad
      Sci USA 2000;97:10272]. Our results demonstrated that COX-1 (and not COX-2) was
      the primary isoform involved in nociception in both model systems. Given the
      importance of dorsal root ganglia (DRG) in pain transmission we examined the
      expression patterns of COX-1, -2 and the recently described variant of COX-1
      retaining intron-1, originally referred to as "COX-3" but hereafter referred to
      as COX-1 variant (COX-1v), in mouse L4 or L5 DRG taken from normal and COX
      isozyme-deficient mice. Messenger RNA and protein for COX isoforms from DRG,
      spinal cord as well as, heart, brain, kidney, spleen and skin of adult mice were
      isolated and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and Western blot analysis, respectively. Patterns of COX-isoform expression were
      determined using immunohistochemical techniques. We found that COX-1 and COX-1v
      were both expressed in neurons while COX-2 expression was completely undetectable
      in the DRG. Immunohistochemical analysis of COX expression in DRG of mice
      exhibiting the chronic pain and inflammation associated with collagen-induced
      arthritis (CIA) expressed COX-1 and COX-1v while no COX-2 could be detected. For
      purposes of comparison, COX-1v mRNA was also expressed in heart, brain, spinal
      cord, kidney, spleen and skin. Together, these data support a role for COX-1 and
      perhaps COX-1v, not COX-2, as the primary producers of PGs in mouse DRG in normal
      and in mice subject to chronic pain and inflammation. These data also suggest
      potential alternative analgesic mechanisms of action for the newly developed, COX
      2 selective inhibitors and the nonsteroidal anti-inflammatory drugs (NSAIDs) in
      pain transmission in the peripheral nervous system.

PMID- 15560115
TI  - Effects of estrous synchronization on response to nitric oxide donors, nitric
      oxide synthase inhibitors, and endothelin-1 in vitro.
AB  - Two experiments were conducted to determine the effects of nitric oxide (NO)
      donors, endothelin-(ET-1), and NO synthase (NOS) inhibitors on bovine luteal
      function in vitro. In experiment 1, estrus in Brahman cows was synchronized with
      Synchro-Mate-B (SMB) and day-13-14 corpora luteal slices were weighed, diced and
      incubated in vitro. Treatments (100 ng/ml) were: vehicle, N[see symbol in text]
      nitro-L-arginine-L-methyl ester (L-NAME), N(G)-monomethyl-L-arginine acetate (L
      NMMA), diethylenetriamine (DETA), DETA-NONOate, sodium nitroprusside (SNP), or ET
      1. In experiment 2, estrus was synchronized with Lutalyse, a Controlled
      Intravaginal Progesterone Releasing Device (CIDR), or cows were not synchronized.
      Corpora lutea were collected, weighed, and luteal slices were weighed, diced and
      incubated in vitro with treatments. Treatments (100ng/ml) were: vehicle, L- NAME,
      L-NMMA, DETA, DETA-NONOate, sodium nitroprusside, S-nitroso-N-acetylpenicillamine
      (SNAP) or endothelin-1. Tissues were incubated in M- 199 for 1 h without
      treatments and for 4 and 8 h in both experiments with treatments in both
      experiments. Media were analyzed for progesterone, prostaglandins E2 and F2alpha
      (PGE2, PGF2alpha) by radioimmunoassay (RIA). Hormone data in experiments 1 and 2
      were analyzed by 2 x 7 and 3 x 2 x 8 factorial design for analysis of variance
      (ANOVA), respectively. Luteal weights in experiment 2 were analyzed by a one-way
      ANOVA. Concentrations of progesterone in media were similar (P > or = 0.05) among
      treatments within experiments. Concentrations of PGE2 in media in experiment 1
      were undetectable in 90 and 57% of the samples at 4 and 8 h, respectively.
      PGF2alpha increased (P < or = 0.05) with time, but did not differ (P > or = 0.05)
      among treatments. Secretion of PGF2alpha was not affected by treatments (P > or =
      0.05). In experiment 2, luteal weights of the induced estrous cycle were
      decreased (P < or = 0.05) by Lutalyse. Concentrations of PGE2 and PGF2alpha
      increased (P < or = 0.05) with time in control of all three synchronization
      regimens. DETA-NONOate, SNAP, sodium nitroprusside (NO donors) and ET-1 increased
      (P < or = 0.05) PGE2 except in the CIDR synchronized group (P > or = 0.05). No
      treatment increased (P > or = 0.05) PGF2alpha in any synchronization regimen. It
      is concluded that either SMB containing norgestomet or a CIDR containing
      progesterone alters luteal secretion of PGE2, Lutalyse lowers luteal weights in
      the induced estrous cycle, and NO or ET-1 given alone are not luteolytic agents.
      It is suggested that NO and ET-1 could have indirect antiluteolytic/luteotropic
      effects via increasing PGE2 secretion by luteal tissue rather than being
      luteolytic.

PMID- 15560116
TI  - The induction of prostaglandin E synthase and upregulation of cyclooxygenase-2 by
      9-cis retinoic acid.
AB  - 9-cis Retinoic acid (9cRA) is a promising lead compound to design the retinoid X
      receptor (RXR) ligands with the ability to simultaneously activate RXR
      heterodimers with the selectivity to their nuclear receptor partners. In this
      study, we investigated the effects of 9cRA on the prostaglandin E2 (PGE2) and
      thromboxane A2 (TXA2) production. 9cRA increased the PGE2 and TXA2 productions in
      the presence of lipopolysaccharide (LPS). All-trans retinoic acid, the retinoic
      acid receptor ligand, also increased their production. We revealed that
      cyclooxygenase (COX)-2 was clearly induced by 9cRA in the presence of LPS. The
      induction was not suppressed by indomethacin, which completely inhibited the
      increase in the LPS-stimulated prostanoid production by 9cRA. The expression
      levels of the toll-like receptor 4 and CD14, which were components of the LPS
      receptor complex, were increased by 9cRA in the presence and absence of LPS. PGE
      synthase was also clearly increased by 9cRA in the presence and absence of LPS.
      In this study, we noted that 9cRA increased the production of PGE2 and TXA2 by
      the induction of COX-2 and PGE synthase in the presence of LPS. The induction of
      the LPS receptor complex by 9cRA is able to upregulate the induction of COX-2 by
      LPS.

PMID- 15560117
TI  - Pharmacological evaluation of both enantiomers of (R,S)-BM-591 as thromboxane A2
      receptor antagonists and thromboxane synthase inhibitors.
AB  - The aim of this work is to evaluate the anti-thromboxane activity of two pure
      enantiomers of (R,S)-BM-591, a nitrobenzene sulfonylurea chemically related to
      torasemide, a loop diuretic. The drug affinity for thromboxane A2 receptor (TP)
      of human washed platelets has been determined. In these experiments, (R)-BM-591
      (IC50 = 2.4+/-0.1 nM) exhibited a significant higher affinity than (S)-BM-591
      (IC50 = 4.2+/-0.15 nM) for human washed platelets TP receptors. Both enantiomers
      were stronger ligands than SQ-29548 (IC50 = 21.0+/-1.0 nM) and sulotroban (IC50 =
      930+/-42 nM), two reference TXA2 receptor antagonists. Pharmacological
      characterisations of (S)-BM-591 and (R)-BM-591 were compared in several models.
      Thus, (R)-BM-591 strongly prevented platelet aggregation induced by arachidonic
      acid (AA) (600 microM) and U-46619 (1 microM) while (S)-BM-591 showed a lower
      activity. On isolated tissues pre-contracted by U-46619, a stable TXA2 agonist,
      (S)-BM-591 was more potent in relaxing guinea-pig trachea (EC50 = 0.272+/-0.054
      microM) and rat aorta (EC50 = 0.190+/-0.002 microM) than (R)-BM-591 (EC50 of
      9.60+/-0.63 microM and 0.390+/-0.052 microM, respectively). Moreover, at 1
      microM, (R)-BM-591 totally inhibited TXA2 synthase activity, expressed as TXB2
      production from human platelets, while at the same concentration, (S)-BM-591
      poorly reduced the TXB2 synthesis (22%). Finally, in rats, both enantiomers lost
      the diuretic activity of torasemide. In conclusion, (R)-BM-591 exhibits a higher
      affinity and antagonism on human platelet TP receptors than (S)-BM-591 as well as
      a better thromboxane synthase inhibitory potency. In contrast, (S)-BM-591 is more
      active than the (R)-enantiomer in relaxing smooth muscle contraction of rat aorta
      and trachea guinea pig. Consequently, (R)-BM-591 represents the best candidate
      for further development in the field of thrombosis disorders.

PMID- 15560118
TI  - Inhibition of phorbol ester-induced PGF2alpha secretion by IFN-tau is not through
      regulation of protein kinase C.
AB  - Inhibitory effect of IFN-tau on phorbol ester (PdBu)-induced PGF2alpha secretion
      was hypothesized to be manifested by the regulation of protein kinase C (PKC) in
      bovine endometrial (BEND) cells. Following 12 h stimulation with PdBu, cells were
      unresponsive to freshly added PdBu. Pretreatment of cells with a PKC inhibitor
      abolished PGF2alpha secretion in response to PdBu. Therefore, PdBu induction of
      PGF2alpha secretion is through activation of PKC. The alpha, epsilon, iota and
      lambda isotypes of the PKC family were identified by Western blotting. Cells were
      then treated with medium alone (control), PdBu or PdBu + IFN-tau for 3 or 6 h.
      The PdBu-induced secretion of PGF2alpha was suppressed by IFN-tau. At 3 and 6 h,
      PKCalpha and PKCepsilon were detected both in the cytosolic and membrane
      fractions of unstimulated cells. There was a clear reduction of PKCalpha in the
      cytoplasm induced by PdBu and PdBu + IFN-tau at 3 and 6 h. The total abundance
      (cytoplasm and membrane fractions) of PKCalpha was lower in the PdBu + IFN-tau
      than PdBu alone. These temporal responses indicate a PKCalpha responsiveness of
      BEND cells to PdBu and PDBu + INF-tau with some evidence that IFN-tau causes a
      slight but detectable reduction in PKCalpha when added with PdBu. However, IFN
      tau-induced decrease in the total abundance of PKCalpha was not enough to affect
      negatively the translocation of the PKCalpha to the membrane. Therefore, IFN
      tau's ability to suppress secretion of PGF2alpha is unlikely due to an
      interference with the PdBu-induced activity of PKC.

PMID- 15560119
TI  - Vasoconstriction induced by activation of EP1 and EP3 receptors in human lung:
      effects of ONO-AE-248, ONO-DI-004, ONO-8711 or ONO-8713.
AB  - This study investigated the effects and selectivity of ONO-AE-248, ONO-DI-004,
      ONO-8711 and ONO-8713 on EP1 and EP3 receptors in human pulmonary vessels. The
      prostanoid receptors involved in the vasoconstriction of human pulmonary arteries
      (HPA) are TP and EP3 whereas in pulmonary veins (HPV), this response is
      associated with TP and EP1. The experiments were performed in presence of BAY
      u3405 (TP antagonist). ONO-DI-004 (EP1 agonist) and ONO-AE-248 (EP3 agonist),
      exhibited little or no activity in HPV whereas contractions were induced in HPA
      with ONO-AE-248. In HPV, the contractions produced with sulprostone (EP1,3
      agonist) were blocked in a non competitive manner by both EP1 antagonists (ONO
      8711, 30 microM; ONO-8713, 10 microM). The involvement of EP1 mediated
      contraction in HPV was also observed during the vasorelaxations induced with PGE1
      and 5-cis-carba-PGI2. In pre-contracted HPV treated with AH6809 (30 microM; EP1
      antagonist) the PGE1 vasorelaxations were potentiated, while unchanged in HPA.
      These results demonstrate the selectivity of ONO-AE-248 for the EP3 receptor in
      HPA, ONO-DI-004 was ineffective on the EP1 receptor present in HPV while ONO-8713
      was the more potent EP1 antagonist used in this tissue.

PMID- 15560120
TI  - PGE2 exerts its effect on the LPS-induced release of TNF-alpha, ET-1, IL-1alpha,
      IL-6 and IL-10 via the EP2 and EP4 receptor in rat liver macrophages.
AB  - Lipopolysaccharide (LPS) induces a release of tumor necrosis factor (TNF)-alpha,
      endothelin (ET)-1, interleukin (IL)-1alpha, IL-6 and IL-10 in rat liver
      macrophages (Kupffer cells). Prostaglandin (PG)E2 inhibits the release of the
      fibrogenic mediators TNF-alpha, ET-1 and IL-1alpha, and enhances the release of
      the anti-fibrogenic mediators IL-6 and IL-10. This effect of PGE2 is mimicked by
      specific agonists for the PGE2 receptors EP2 and EP4; whereas, agonists for the
      PGE2 receptors EP1 and EP3 are inactive. Rat liver macrophages express mRNA
      encoding the PGE2 receptors EP2 and EP4 but not the PGE2 receptors EP1 and EP3.
      These data suggest that PGE2 exerts its anti-fibrogenic effect through the EP2
      and EP4 receptor by inhibiting the release of the fibrogenic mediators TNF-alpha,
      ET-1 and IL-1alpha, and by enhancing the release of the anti-fibrogenic mediators
      IL-6 and IL-10 in liver macrophages.

PMID- 15560121
TI  - Synergism between cysteinyl leukotrienes and thromboxane A2 to induce allergic
      late phase nasal blockage in guinea pigs.
AB  - We examined whether cysteinyl leukotrienes (CysLTs) and thromboxane (TX) A2 are
      synergistically involved in a cedar pollen-induced allergic late phase nasal
      blockage in guinea pigs. Sensitized animals were repeatedly challenged by pollen
      inhalation once every week. Combined treatment with pranlukast (a CysLT
      antagonist) and seratrodast (a TXA2 antagonist) inhibited late phase nasal
      blockage, but the magnitude of inhibition (approximately 50%) was equal to those
      of the respective single treatments, suggesting that CysLTs produced late after
      challenge induces TXA2 production in the nasal tissue, as in the case of the lung
      of this species. However, pranlukast did not affect TXB2 increase in the nasal
      tissue. In contrast, combined intranasal instillation of LTD4 and U-46619 (a TXA2
      mimetic) produced much greater nasal blockage than single administration of each
      agonist in sensitized animals. Therefore, allergic late phase nasal blockage
      should be induced by synergistic activity of CysLTs and TXA2 at the effector
      organ.

PMID- 15560122
TI  - Report on the discovery of a novel 3-hydroxy oxylipin cascade in the yeast
      Saccharomycopsis synnaedendra.
AB  - A novel cascade of 3-hydroxy fatty acids was discovered in the yeast
      Saccharomycopsis synnaedendra. The cascade, probably derived from incomplete beta
      oxidation, comprises both even and uneven carbon numbered as well as saturated
      and unsaturated 3-hydroxy oxylipins. This yeast may now be used as model to
      further study the metabolism of these compounds as well as their biotechnological
      production.

PMID- 15560123
TI  - Separation technologies. Supporting solutions.

PMID- 15560124
TI  - Cost-effective trapezoidal modified Boyden chamber with comparable accuracy to a
      commercial apparatus.

PMID- 15560125
TI  - Preparation of chimeric genes without subcloning.

PMID- 15560126
TI  - High-throughput extraction of arthropod vector and pathogen DNA using bead
      milling.

PMID- 15560127
TI  - Simplified method for gene targeting vector construction.

PMID- 15560128
TI  - Improved expression vector for Brucella species.

PMID- 15560129
TI  - Method based on electrophoresis and gel extraction for obtaining genomic DNA-free
      cDNA without DNase treatment.

PMID- 15560130
TI  - LINE-1 insertion dimorphisms identification by PCR.

PMID- 15560131
TI  - Protocol for amplification of GC-rich sequences from Pseudomonas aeruginosa.

PMID- 15560132
TI  - Reliable method for generating double-stranded DNA vectors containing site
      specific base modifications.
AB  - Cells of all living organisms are continuously exposed to physical and chemical
      agents that damage DNA and alter the integrity of their genomes. Despite the
      relatively high efficiency of the different repair pathways, some lesions remain
      in DNA when it is replicated or transcribed. Lesion bypass by DNA and RNA
      polymerases has been the subject of numerous investigations. However, knowledge
      of the in vivo mechanism of transcription lesion bypass is very limited because
      no robust methodology is available. Here we describe a protocol based on the
      synthesis of a complementary strand of a circular, single-stranded DNA molecule,
      which allows for the production of large amounts of double-stranded DNA
      containing a lesion at a specific position in a transcribed sequence. Such
      constructs can subsequently be used for lesion bypass studies in vivo by RNA
      polymerase and to ascertain how these events can be affected by the genetic
      background of the cells.

PMID- 15560133
TI  - In silico gene selection strategy for custom microarray design.
AB  - Microarray technology has become an important tool for studying large-scale gene
      expression for a diversity of biological applications. However, there are a
      number of experimental settings for which commercial arrays are either unsuitable
      or unavailable despite the existence of sequence information. With the increasing
      availability of custom array manufacturing services, it is now feasible to design
      high-density arrays for any organism having sequence data. However, there have
      been relatively few reports discussing gene selection, an important first step in
      array design. Here we propose an in silico strategy for custom microarray gene
      selection that is applicable to a wide range of organisms, based on utilizing
      public domain microarray information to interrogate existing sequence data and to
      identify a set of homologous genes in any organism of interest. We demonstrate
      the utility of this approach by applying it to the selection of candidate genes
      for a custom Xenopus laevis microarray. A significant finding of this study is
      that 3%-4% of Xenopus expressed sequence tags (ESTs) are in an orientation
      contrary to that indicated in the public database entry
      (http://mssaha.people.wm.edu/suppMSS.html).

PMID- 15560134
TI  - PicoGmeter, a custom-made fluorometer for the quantification of dsDNA by
      PicoGreen fluorescence.
AB  - The accurate determination of DNA concentration is essential for many processes
      in molecular biology and physiology and includes both gel- and cuvette-based
      methods. The recently introduced fluorescent dye, PicoGreen, has several
      advantages over other methods because it is sensitive and specific for double
      stranded DNA (dsDNA). The dye is excited at 480 nm and emits at 520 nm when bound
      to dsDNA. This report describes the construction and use of PicoGmeter, a simple,
      inexpensive, fixed-wavelength fluorometer suitable for measuring PicoGreen
      fluorescence. PicoGmeter employs a blue light emitting diode (LED) for excitation
      and a photodiode to measure fluorescence. When compared to a commercially
      available instrument, PTI DeltaScan, the PicoGmeter performed admirably.
      Calibration curves for both instruments were superimposeable. Moreover, there was
      no significant difference between concentrations of DNA estimated by both
      instruments. A Bland and Altman analysis revealed that the PicoGmeter was
      equivalent to the PTI DeltaScan for estimating dsDNA concentration by the
      PicoGreen method. This simple, inexpensive, battery-operated fluorometer will
      allow investigators to employ the PicoGreen method without incurring the cost of
      purchasing a spectrofluorometer.

PMID- 15560135
TI  - Glutaraldehyde: behavior in aqueous solution, reaction with proteins, and
      application to enzyme crosslinking.
AB  - Glutaraldehyde possesses unique characteristics that render it one of the most
      effective protein crosslinking reagents. It can be present in at least 13
      different forms depending on solution conditions such as pH, concentration,
      temperature, etc. Substantial literature is found concerning the use of
      glutaraldehyde for protein immobilization, yet there is no agreement about the
      main reactive species that participates in the crosslinking process because
      monomeric and polymeric forms are in equilibrium. Glutaraldehyde may react with
      proteins by several means such as aldol condensation or Michael-type addition,
      and we show here 8 different reactions for various aqueous forms of this reagent.
      As a result of these discrepancies and the unique characteristics of each enzyme,
      crosslinking procedures using glutaraldehyde are largely developed through
      empirical observation. The choice of the enzyme-glutaraldehyde ratio, as well as
      their final concentration, is critical because insolubilization of the enzyme
      must result in minimal distortion of its structure in order to retain catalytic
      activity. The purpose of this paper is to give an overview of glutaraldehyde as a
      crosslinking reagent by describing its structure and chemical properties in
      aqueous solution in an attempt to explain its high reactivity toward proteins,
      particularly as applied to the production of insoluble enzymes.

PMID- 15560136
TI  - Fluorescence anisotropy microplate assay for analysis of steroid receptor-DNA
      interactions.
AB  - To analyze the interactions of steroid/nuclear hormone receptors with their DNA
      response elements, we used ultra low-volume microplates to develop a simple and
      rapid fluorescence anisotropy assay. The novel fluorescence anisotropy microplate
      assay (FAMA) was applied to the binding of estrogen and progesterone receptors
      (ER and PR, respectively) to their respective DNA response elements. The FAMA
      offers exceptional flexibility in its ability to test a variety of binding
      conditions and DNA response elements in real time. This assay can differentiate
      between, and quantitate, sequence-specific and nonspecific binding of receptors
      to DNA and offers the possibility of true solution analysis of the interaction of
      coregulators with the estrogen response element (ERE)-ER complex. To test
      suitability for screening large compound libraries, we demonstrated that the FAMA
      generates stable signals for more than 4 hours, is insensitive to inhibition by
      dimethyl sulfoxide (DMSO), and works well in 384-well plates. We analyzed
      inhibition of receptor-DNA interaction by several zinc chelators and demonstrated
      zinc dependence and a generally higher sensitivity to inhibition for PR
      progesterone response element (PRE) interactions than for ER-ERE interactions.
      The FAMA is the first system suitable for screening large compound libraries to
      identify novel compounds that antagonize (or stimulate) binding of steroid
      receptors to their DNA response elements.

PMID- 15560137
TI  - High-throughput screening of suppression subtractive hybridization cDNA libraries
      using DNA microarray analysis.
AB  - Efficient construction of cDNA libraries enriched for differentially expressed
      transcripts is an important first step in many biological investigations. We
      present a quantitative procedure for screening cDNA libraries constructed by
      suppression subtractive hybridization (SSH). The methodology was applied to two
      independent SSHs from pearl millet and banana. Following two-color cyanin dye
      labeling and hybridization of subtracted tester with either unsubtracted driver
      or unsubtracted tester cDNAs to the SSH libraries arrayed on glass slides, two
      values were calculated for each clone, an enrichment ratio 1 (ER1) and an
      enrichment ratio 2 (ER2). Graphical representation of ER1 and ER2 enabled the
      identification of clones that were likely to represent up-regulated transcripts.
      Normalization of each clone by the SSH process was determined from the ER2
      values, thereby indicating whether clones represented rare or abundant
      transcripts. Differential expression of pearl millet and banana clones identified
      from both libraries by this quantitative approach was verified by inverse
      Northern blot analysis.

PMID- 15560138
TI  - Comparison of two probe preparation methods using long oligonucleotide
      microarrays.
AB  - The use of oligonucleotides as a capture platform for microarray-based
      experiments is gaining popularity. Oligonucleotide-based microarrays involving
      various probe preparations have been compared by a number of researchers. Limited
      data are available, however, regarding the concordances and efficacies of various
      probe preparations on long oligonucleotide-based microarrays. Accordingly, the
      current investigation assesses two labeling methods, namely Atlas PowerScript
      fluorescent cDNA (random priming) and T7 in vitro transcription cRNA [poly(T)
      priming] labeling kits. Our data revealed that a high degree of reproducibility
      among the examined genes for each assay used with correlation coefficients of
      0.93 and 0.94 for random priming and poly(T) priming, respectively. It is worthy
      of note, however, that when the two assaying methods were compared, the data
      showed a poor correlation coefficient. A confirmatory step involving real-time
      reverse transcription PCR (RT-PCR) of 18 selected genes favors the superiority of
      the cDNA fluorescent labeling over the T7 labeling method. Overall, the
      microarray results generated by the poly(T) priming methodology should be viewed
      cautiously even when high reproducibility is evident.

PMID- 15560139
TI  - S-peptide epitope tagging for protein purification, expression monitoring, and
      localization in mammalian cells.
AB  - Epitope tags are widely used in cell biology and biochemistry research. The S
      peptide/S-protein interaction has previously been utilized to purify polypeptides
      expressed in bacteria. We have now re-engineered the S-peptide/S-protein system
      to allow isolation of S-peptide-tagged polypeptides and their binding partners
      from eukaryotic cells with S-protein-agarose. In addition, two anti-S-peptide
      monoclonal antibodies have been generated for analysis of expression and
      subcellular localization of S-peptide-tagged polypeptides. These reagents make
      the S-peptide/S-protein system an attractive alternative to currently available
      epitope tagging methods.

PMID- 15560140
TI  - "One plate/three-reporter" assay format for the detection and validation of yeast
      two-hybrid interactions.
AB  - We describe a novel assay format for the Gal4-based yeast two-hybrid-system, in
      which the readout from three different reporter genes is measured sequentially in
      a single microplate. Activation of the URA3, MEL1, and lacZ reporters in response
      to a protein-protein interaction is monitored by measuring sequentially: (i)
      growth in medium lacking uracil, (ii) alpha-galactosidase activity, and (iii)
      beta-galactosidase. The data thus generated permit elimination of many false
      positive signals and provide a preliminary measurement of reporter activation
      strength that may be confirmed by further analysis. The assay procedure is
      inexpensive and requires few liquid-handling steps. It is appropriate for
      automated high-throughput interaction mating assays, validation of putative
      interactor strains and hybrid-protein self-activator tests.

PMID- 15560141
TI  - Quenching accumulation of toxic galactose-1-phosphate as a system to select
      disruption of protein-protein interactions in vivo.
AB  - The reverse two-hybrid system has been developed to readily identify molecules or
      mutations that can disrupt protein-protein interactions in vivo. This system is
      generally based on the interaction-dependent activation of a reporter gene, whose
      product inhibits the growth of the engineered yeast cell. Thus, disruption of the
      interaction between the hybrid proteins can be positively selected because, by
      reducing the expression of the negative marker gene, it allows cell growth.
      Although several counter-selectable marker genes are currently available, their
      application in the reverse two-hybrid system is generally confronted with
      technical and practical problems such as low selectivity and relatively complex
      experimental procedures. Thus, the characterization of more reliable and simple
      counter-selection assays for the reverse two-hybrid system continues to be of
      interest. We have developed a novel counter-selection assay based on the toxicity
      of intracellular galactose-1-phosphate, which accumulates upon expression of a
      galactokinase-encoding GAL1 reporter gene in the absence of transferase activity.
      Decreased GAL1 gene expression upon dissociation of interacting proteins causes
      reduction of intracellular galactose-1-phosphate concentrations, thus allowing
      cell growth under selective conditions.

PMID- 15560142
TI  - Linear mRNA amplification from as little as 5 ng total RNA for global gene
      expression analysis.
AB  - Gene expression analysis has become an invaluable tool for understanding gene
      function and regulation. However, global expression analysis requires large RNA
      quantities or RNA preamplification. We describe an isothermal messenger RNA
      (mRNA) amplification method, Ribo-SPIA, which generates micrograms of labeled
      cDNA from 5 ng of total RNA in 1 day for analysis on arrays or by PCR
      quantification. Highly reproducible GeneChip array performance (R2 > 0.95) was
      achieved with independent reactions starting with 5-100 ng Universal Human
      Reference total RNA. Targets prepared by the Ribo-SPIA procedure (20 ng total RNA
      input) or the Affymetrix Standard Protocol (10 microg total RNA) perform
      similarly, as indicated by gene call concordance (86%) and good correlation of
      differential gene expression determination (R2 = 0.82). Accuracy of transcript
      representation in cDNA generated by the Ribo-SPIA procedure was also demonstrated
      by PCR quantification of 33 transcripts, comparing differential expression in
      amplified and nonamplified cDNA (R2 = 0.97 over a range of nearly 10(6) infold
      change). Thus Ribo-SPIA amplification of mRNA is rapid, robust, highly accurate
      and reproducible, and sensitive enough to allow quantification of very low
      abundance transcripts.

PMID- 15560143
TI  - Aging with health and dignity.

PMID- 15560144
TI  - Home care & LTC insurance: can a match be made?

PMID- 15560145
TI  - Home care options to expand for dependents of military personnel & veterans.

PMID- 15560146
TI  - Growing expenditures and new trends could change Medicare hospice benefit.

PMID- 15560147
TI  - State efforts toward creating a national policy on healthy aging and long-term
      care.
AB  - The Honorable Dirk Kempthorne served Idaho as a U.S. senator for six years prior
      to his election as governor in 1998. He has since served in this role with marked
      distinction--one poll lauded him as Idaho's "most popular figure" in the state's
      history. His leadership capabilities were recognized by the National Governors
      Association (NGA), which elected him chairman in 2003. Upon his election, Gov.
      Kempthorne asserted--and the NGA collectively agreed--to make long-term care for
      America's seniors and persons with disabilities the No. 1 item on the NGA agenda.
      Idaho's governor has since led the NGA through a series of hearings and fact
      finding missions on long-term care culminating in a report that comprised the
      central focus of the NGA's Annual Meeting in July 2004. The following is a
      summary of Gov. Kempthorne's statements regarding long-term care and the reports
      he presented on the topic at that gathering. In recognition of his work, the
      Idaho governor has been selected to receive NAHC's highest accolade--The Claude
      Pepper Award--presented annually to the one person who has done the most to
      promote the interests of senior citizens and persons with disabilities within the
      past year.

PMID- 15560148
TI  - Private equity groups take an interest in home health.

PMID- 15560149
TI  - Remote communications make providers & patients increasingly able to connect.

PMID- 15560150
TI  - Changing is tough... Not terminal.

PMID- 15560151
TI  - Seven simple steps to enhance the written word.

PMID- 15560152
TI  - Preventive medicine for "compassion fatigue".

PMID- 15560153
TI  - A time of transcendence... A time of celebration.

PMID- 15560154
TI  - [Nephrureterectomy with endoscopic resection of the urinary bladder, ureteral
      ostium and terminal part in papillary tumors of the upper urinary tracts].
AB  - Short- and long-term results of endoscopically assisted nephrureterectomy were
      studied in 15 patients (7 males and 8 females aged 31-79 years) with papillary
      tumours of the upper urinary tracts (UUT). Of them, 11 patients have undergone
      transurethral endoresection of the urinary bladder, ostium and terminal part of
      the ipsilateral ureter followed by nephrureterectomy from the lumbotomic approach
      (technique 1) and 4 patients had nephrureterectomy followed by endoscopic
      intervention (technique 2). Results of standard open nephrureterectomy with
      resection of the bladder were analyzed retrospectively for 25 patients with
      papillary tumors of the UUT taken as control. It was found that transurethral
      endoscopic resection of the bladder, ostium and terminal part of the ipsilateral
      ureter in nephrureterectomy for papillary tumors of the UUT facilitates the
      performance, decreases duration and aggression of surgical intervention,
      diminishes number of complications, shortens hospital stay of the patients and
      their rehabilitation. Technique 1 is thought more ablastic and simple in
      performance.

PMID- 15560155
TI  - [Morphological changes in prostatic tissue of patients with benign prostatic
      hyperplasia treated with permixon].
AB  - A pilot trial has been performed to assess effects of permixon on prostatic
      tissue in patients with benign prostatic hyperplasia (BPH). A total of 49 BPH and
      control patients entered the trial. 36 patients of the study group were
      randomized into 3 subgroups of 12 patients each. Permixon was taken in a standard
      dose of 320 mg/day for 3, 6 and 12 months, respectively. Mean duration of BPH was
      3.7 years (0-8 years). Mean value of PCA was 6.0 ng/ml. The control group of 13
      patients were not given permixon. Multifocal prostatic biopsy was performed in
      all the patients before and after the treatment or follow-up. Stromal
      parenchymatous correlation in the study group significantly increased (by 59%)-
      from 3.28 (0.25-9.61) to 5.22 (1.20-10.67) (p = 0.0002). For the control group
      this correlation was insignificant. Permixon-treated patients demonstrated
      inhibition of prostatic epithelium proliferative activity by 32% (p = 0.0001) and
      a rise in the stage of proliferative centers development from stage II-III to IV
      V. Intensity of inflammation in prostatic tissue decreased by 53% in the study
      group and insignificantly in the control group. Thus, permixon treatment of BPH
      leads to a significant rise in stromal-parenchymatous correlation due to
      inhibition of proliferative activity of prostatic epithelium and attenuation of
      inflammation.

PMID- 15560156
TI  - [Urogenital tuberculosis: problems of present-day diagnosis and treatment].
AB  - The analysis of 4904 cases with tuberculosis admitted to the urological
      department of Moscow tuberculosis hospital N 7 in 1996-2002 showed increased
      incidence of new-onset and recurrent urogenital tuberculosis--the share has risen
      from 2.1 to 7.8%. Of 267 new cases, 49.4% had severe destructive forms. The
      disease manifested with chronic cystitis in 35 (13.11%), subacute
      orchoepidydimitis in 35 (13.11%), anatomofunctional alterations of the kidneys
      (hydronephrotic transformation, non-functioning kidney, ureteritis, etc.) in 76
      (28.46%) patients. Bacterial discharge occurred in 52% of new cases. The
      diagnosis was based on clinical and x-ray data in 48%. Isolated genital
      tuberculosis, isolated nephrotuberculosis and their combination were revealed in
      14.23, 59.57 and 26.2% patients, respectively. Among the patients with advanced
      destructive forms 75% got disabled completely. This fact indicates the importance
      of early diagnosis and adequate etiotropic therapy. Active urogenital
      tuberculosis was treated surgically in 51% patients, most of the operations were
      made for marked destructive processes in the kidneys. The organ-removing
      operations were conducted in 73% of them. Preoperative tuberculostatic therapy
      reduced frequency of postoperative complications. In early diagnosis, the organ
      was saved in operations in 9.38%. It is recommended to refer patients to the
      phthisiourologist to be examined for urogenital tuberculosis if they have long
      standing urogenital infection, destructive lesions of the upper urinary tracts,
      calculous prostatitis.

PMID- 15560157
TI  - [Antibacterial therapy of complicated urinary infections in outpatients].
AB  - The term complicated urinary infections (CUIs) includes infections developing in
      the presence of anatomic anomalies, metabolic or hormonal disorders,
      immunodeficiency or infection with atypical microorganisms. Complicating factors
      diminish efficiency of antibiotic treatment, raise probability of recurrence.
      CUIs account for 45.2% of all cases of outpatient urinary infections in adults in
      Russia. Nephroliths, diabetes mellitus and renal cysts are most prevalent
      complicating factors. CUIs causative agents' spectrum is wider and resistance
      bacteria isolation is more frequent compared to uncomplicated urinary infections.
      In addition to antibiotic therapy, CUIs treatment should be focused on detection
      and elimination of the complicating factor. If complicating factors are
      unremovable, antibiotic therapy should be directed to management of clinical
      symptoms of urinary infection, prevention of complications and damage to renal
      parenchyma. CUIs demand longer courses of antibiotics than uncomplicated urinary
      infections: 7-14 days in infection of the lower urinary tracts, at least 14 days
      in infection of the upper urinary tracts and 4-6 weeks in failure of the standard
      course. Fluoroquinolones are drugs of choice in adults.

PMID- 15560158
TI  - [Naiz (nimesulid) in combined treatment of patients with chronic non-bacterial
      prostatitis with chronic pelvic pain syndrome].
AB  - Naiz (nimesulid) was given to 46 patients (age 24-52 years) with chronic
      abacterial prostatitis suffering from chronic pelvic pain syndrome (CPPS) which
      appeared from 20 to 3 years before the treatment. Microscopy of prostatic
      secretion showed normal count of leukocytes. Transrectal ultrasound investigation
      with dopplerography has found normal echostructure of the prostate but blood flow
      parameters were subnormal. Naiz was given in a dose 100 mg (1 tablet) twice a day
      for 15-20 days. The treatment relieved pain in 68-87% patients (mean 77.5%). The
      control ultrasound investigation detected much better circulation. Quality of
      life improved significantly. Side effects were mild. The effect persisted for 3
      months of the follow-up. Thus, the addition of such nonsteroid antiinflammatory
      drug as naiz (nimesulid) to treatment of patients with chronic abacterial
      prostatitis is justified. The drug improves quality of life, induces side effects
      rarely and can be used for a long time with a persistent efficacy.

PMID- 15560159
TI  - [Apparatus Aeltis-Synchro-02-"Yarilo" and vacuum laser therapeutic urologic
      massager AMVL 01-"Yarovit in the treatment of chronic prostatitis complicated
      with copulation disfunction].
AB  - There are three directions in pathogenetic treatment of chronic prostatitis (CP)
      which is conducted in parallel to etiotropic one (antimicrobial): general
      immunological; improving arterial inflow and venous outflow; creation of
      prostatic secretion outflow and that of seminal vesicles by means of contractions
      of the pelvic and perineal muscles, muscular fibers of the prostatic gland. The
      latter two directions can be managed with physiotherapy. It is proposed to use
      combination of drugs with physiotherapy conducted by means of the devices [see
      text].

PMID- 15560160
TI  - [Ejaculate microflora sensitivity to lactoferrin in chronic prostatitis].
AB  - To determine an antimicrobial action of lactoferrin on bacterial flora of
      ejaculate in chronic prostatitis, we examined 124 patients with various diseases
      of male reproductive system at the age between 17 and 56. A total of 280 strains
      were used as test microorganisms (MO). Sensitivity of the latter to lactoferrin
      was studied with a human lactoferrin apoform. MO isolated from patients with
      marked dysbiosis were resistant to lactoferrin (94%). MO, not leading in cenosis,
      were more sensitive to lactoferrin than MO of the main colonies grown after
      seeding. Reproductive dysfunction was accompanied by higher occurrence of strains
      resistant to lactoferrin. The least sensitivity to lactoferrin was registered in
      asthenozoospermia. Lactoferrin resistance of MO may raise MO pathogenicity. When
      lactoferrin-resistant strains predominate in microbiocenosis, it is an
      unfavourable prognostic sign in relation to development of complications,
      primarily subfertility.

PMID- 15560161
TI  - [Extracorporeal shock-wave therapy in Peyronie's disease].
AB  - The aim of the study was to validate clinical methodology on application of shock
      wave impact on plaques in Peyronie's disease (PD). We studied short- and long
      term results of extracorporeal shock-wave therapy (ESWT) in 54 patients 3, 6 and
      12 months after the exposure. We performed ESWT sessions on different
      lithotriptors using different mechanisms of shock wave mechanism (hydromechanical
      and piezoelectric). Choice of the ESWT technique was based on the thickness and
      density of the plaque. The proposed ESWT method provides an effective treatment
      of the disease basing on the initial angle of penis deformation in erection.

PMID- 15560162
TI  - [Viagra, cialis, impase--which of them, to whom, when and how?].
AB  - The study has been performed of the efficacy in the treatment of erectile
      dysfunction (ED) of oral drugs affecting nitric oxide: impase and
      phosphodiesterase-5 (PDE-5) inhibitors--sildenafil citrate (viagra), tadalafil
      (sialis)--alone and in combination with impase. A total of 218 ED patients aged
      21-73 years (mean age 58.1 +/- 13.2 years) were divided into 3 groups comparable
      by the number of the patients, age, suspected etiology, pathogenesis and ED
      severity. Group 1 (n = 81) took viagra in the individually adjusted dose for 6
      months; group 2 (n = 64) received sialis in a dose 20 mg for 6 months; group 3 (n
      = 73) took impase 1 tablet each other day sublingually for 6 months. Overall
      efficacy made up 77.8, 81.3 and 56.2% for viagra, sialis and impase,
      respectively. In view of different mechanism of action of PDE-5 inhibitors
      (viagra, sialis) and impase we combined the drugs in those who failed monotherapy
      or had drastic side effects. The combination raised efficacy of pharmacotherapy
      from 56.2 to 92.2%. We came to the conclusion that in psychogenic, isolated
      neurogenic, compensated and subcompensated arteriogenic ED of a mild or moderate
      degree, the treatment can be started with impase. If it was uneffective, in
      severe ED or moderate venoocclusive ED it is better to use PDE-5 inhibitors
      (viagra, sialis). If one of the latter fails, the other should be administered.
      If the inhibitors have low efficacy or in side effects, it is indicated to use
      their combination with impase.

PMID- 15560163
TI  - [A new pathogenetic approach and a method of erectile dysfunction treatment and
      prevention--modulated erectile oxygenation of penile cavernous tissue].
AB  - The analysis of sexual activity of 185 male Muscovites has revealed an age
      related sharp progressive shortening of adequate and spontaneous erections. A
      novel, pathogenetically sound approach and a method of therapy and prevention of
      erectile dysfunction has been developed (RF patent N 2228754). The method, called
      "Modulated Erectile Oxygenation of Penile Cavernous Tissue" (MEOPCT), consists in
      erection activation by behavioral measures and/or erectogenic drugs which induce
      adequate, nocturnal spontaneous and/or artificial erections adequate in frequency
      and duration for providing such oxygenation of cavernous bodies that warrants
      maintenance of their normal structure and function. There is no continuous close
      correlation between sexual activity and erections, on the one side, and
      ejaculation and orgasm, on the other side. Application of MEOPCT in 43 patients
      demonstrated the method ability to improve erection and cavernous hemodynamics
      without negative side effects.

PMID- 15560164
TI  - [Immune male infertility: correction with efferent therapy].
AB  - Effects of plasmapheresis and hemosorption on efficacy of the treatment of
      autoimmune male infertility (AMI) were studied in 289 AMI males with
      oligoasthenozoospermia aged 19 to 37 years. The males were divided into three
      groups by the levels of antisperm antibodies (ASAB) in the blood and ejaculate.
      The study was made of cellular and humoral immunity, intensity of protein and
      lipid free radical oxidation and antioxidant defense. Patients of group 1 with
      high ASAB in the blood but low in ejaculate received a course of plasmapheresis.
      Patients of group 2 with high ASAB both in the blood and ejaculate were subjected
      to hemosorption and plasmapheresis in one contour. Group 3 patients with high
      ASAB in ejaculate but low in the blood received efferent therapy only after
      medication and photomodification of the blood. The treatment reduced elevated
      levels of ASAB in the blood and ejaculate, normalized free radical oxidation,
      cellular and humoral immunity, antioxidant defense. This resulted in improvement
      of spermogram parameters, efficacy of assisted reproductive technologies, higher
      probability of natural pregnancy in the patients' wives.

PMID- 15560165
TI  - [Gastrointestinal hormones in the blood serum of patients with chronic renal
      failure].
AB  - Content of gastrointestinal hormones (gastrin, insulin, glucagon, C-peptide),
      beta2-microglobulin, glomerular filtration rate (GFR) were studied in 65 patients
      with nephrolithiasis (NL) and in 73 patients with chronic renal failure (CRF). It
      was found that NL with GFR under 80 ml/min runs with elevated insulin, glucagon
      and C-peptide while CRF with CRF under 30 ml/min is characterized by aggravated
      disorders of hormonal homeostasis (gastrin, insulin, glucagons, C-peptide
      elevation). As gastrointestinal hormones in patients with CRF are high, it is
      recommended to combine medication with diet containing low amount of
      carbohydrates easy for digestion which is important in the treatment of CRF.

PMID- 15560166
TI  - [Peritoneal dialysis in the treatment of chronic renal failure].
AB  - Fifty-four patients were treated with peritoneal dialysis for terminal chronic
      renal failure. Clinical-laboratory indices were assessed in patients on chronic
      peritoneal dialysis. Advantages of continuous ambulatory peritoneal dialysis over
      hemodialysis are analysed in terms of social rehabilitation of the patients.
      Complications of chronic peritoneal dialysis as a method and algorithms of their
      treatment are outlined. The role of peritoneal dialysis as a preparatory stage
      before transplantation of the kidney is assessed.

PMID- 15560167
TI  - [The TVT operation in injury of the pelvic ring].
AB  - The authors report a case of a woman with combination of stress urinary
      incontinence (SUI) with posttraumatic rupture and divergence of the pubic joint.
      The latter led to relaxation of the pelvic base and urethral ligaments resultant
      in SUI. The patient was treated surgically (a modified TVT operation). This rare
      case demonstrates possibility of SUI development consequently to trauma of the
      pelvic ring and a TVT operation efficacy made in non-standard setting.

PMID- 15560168
TI  - [Vesico-appendicular fistula].

PMID- 15560169
TI  - [Treatment of prostatic cancer stage T3N0M0].

PMID- 15560170
TI  - [Application of Paline (pipemidine acid) in urological practice].

PMID- 15560171
TI  - [Tadenan (Pygeum africanum extract) in the treatment of patients with benign
      prostatic hyperplasia].

PMID- 15560172
TI  - [Present-day hypotheses of prostatic cancer etiology and pathogenesis].

PMID- 15560173
TI  - [The subject of urology in the light of current specification of state and legal
      regulation of medical relations].

PMID- 15560174
TI  - Effect of in situ parameters on the enrichment process of MTBE degrading
      organisms.

PMID- 15560175
TI  - Advanced oxidation processes as a driving force for innovation in waste gas
      treatment.

PMID- 15560176
TI  - The effect of temperature and pH on the kinetics of a partial nitritation
      process.

PMID- 15560177
TI  - Development of predictive ecological models for river restoration.

PMID- 15560178
TI  - Optimalization of in-situ LAI determination by means of hemispherical
      photography.

PMID- 15560179
TI  - Cryopreservation of selected ornamentals.

PMID- 15560180
TI  - Water stress induces changes in the proline content and up-regulates the
      activities of anti-oxidant enzymes in tomato leaves.

PMID- 15560181
TI  - Visualisation of particle motion in tapered fluidised bed coating units.

PMID- 15560182
TI  - Dissecting the bacterial stress response against novel challenges: high pressure.

PMID- 15560183
TI  - Characterization of lactoperoxidase stress response in Escherichia coli and
      involvement of corA in lactoperoxidase tolerance.

PMID- 15560184
TI  - Influence of intrinsic factors of apples on the growth and patulin production of
      Penicillium expansum.

PMID- 15560185
TI  - Clostridium-mediated transfer system of therapeutic proteins to solid tumors:
      increased heterologous protein production.

PMID- 15560186
TI  - N2O emission estimates from agricultural soils in Flanders using the BE-DNDC.

PMID- 15560187
TI  - Novel techniques for fast taste profiling of tomatoes.

PMID- 15560188
TI  - Modelling carbon allocation in forest ecosystems: the key role of the carbon
      reserve of trees.

PMID- 15560189
TI  - Stability studies of pectin methylesterase from green bell pepper (Capsicum
      annuum).

PMID- 15560190
TI  - Galloway cattle and horse evaluated as dispersers of plant seeds in nature
      management.

PMID- 15560191
TI  - Flavour enhancement in beer by yeast beta-glucosidase activity.

PMID- 15560192
TI  - Thermal inactivation of strawberry (Fragaria ananassa) polyphenoloxidase--a
      kinetic study.

PMID- 15560193
TI  - Development of migration models for macroinvertebrates in the Zwalm river basin
      as a tool in river assessment and restoration management.

PMID- 15560194
TI  - Calibration and state estimation with soil moisture data in a distributed
      hydrological model.

PMID- 15560195
TI  - Effect of preslaughter fasting combined with stress on plasma hormones and
      metabolites, and meat quality of broilers.

PMID- 15560196
TI  - Development of an artificial promoter library for Escherichia coli.

PMID- 15560197
TI  - Influence of natural antioxidants on the oxidative stability of poultry feed.

PMID- 15560198
TI  - Comparison of egg weight loss during incubation, growth rate, hematocrit and
      heart weights of broilers from three lines differing in ascites susceptibility.

PMID- 15560199
TI  - Resistance to the lactoperoxidase system: role of the lipopolysaccharide layer
      revisited.

PMID- 15560200
TI  - Acrylamide formation during frying of potatoes: thorough investigation on the
      influence of crop and process variables.

PMID- 15560201
TI  - High-pressure homogenisation sensitises Escherichia coli to lysozyme and nisin.

PMID- 15560202
TI  - Use of a temperature-controlled floor: pigs' preferences.

PMID- 15560203
TI  - Insect growth inhibition by N-benzyl chitosan derivatives in the cotton leafworm
      Spodoptera littoralis.

PMID- 15560204
TI  - Micro-algae as potent rumen methane inhibitors and modifiers of rumen lipolysis
      and biohydrogenation of linoleic acid.

PMID- 15560205
TI  - Effect of environmental factors on the calibration curve (OD-CFU) of Listeria
      monocytogenes.

PMID- 15560206
TI  - Asymbiotic germination pattern of D. maculata (Orchidaceae) seeds.

PMID- 15560207
TI  - NDVI measured plant growth variability with conservation tillage, relation with
      limiting resources.

PMID- 15560208
TI  - Effect of storage and cooking on the oxidative stability of pork.

PMID- 15560209
TI  - Hydrological modelling of ungauged catchments in the Scheldt river basin.

PMID- 15560210
TI  - Introduction to speaking plant: let the crop control the greenhouse climate.

PMID- 15560211
TI  - Performance of some varieties of durum wheat (Triticum durum L.) conducted under
      biological and conventional treatments.

PMID- 15560212
TI  - [Study of the morphologic diversity in Detarium microcarpum].

PMID- 15560213
TI  - A micromechanical approach for simulating plant tissue.

PMID- 15560214
TI  - Identification of genes involved in vertical rust resistance in poplar.

PMID- 15560215
TI  - Extraction solvents and sample storage conditions affect content, pattern and
      esterification of fatty acids in fresh grass.

PMID- 15560216
TI  - Rumen and milk fatty acid pattern when feeding forages from intensively managed
      or semi-natural grasslands.

PMID- 15560217
TI  - Effect of temperature and glucose concentration on the kinetics of production of
      butanoyl homoserine lactone by Aeromonas hydrophila.

PMID- 15560218
TI  - Effect of medium chain fatty acids and benzoic acid, as alternatives for
      antibiotics, on growth and some gut parameters in piglets.

PMID- 15560219
TI  - Efficacy of a new boron-based wood preservative compound against fungal decay and
      insect attack.

PMID- 15560220
TI  - Effect of combined high pressure and mild heat on carrot pectinmethylesterase
      activity.

PMID- 15560221
TI  - Probiotic and nutritional effects of microbial communities on axenic cultures of
      a rotifer strain Brachionus plicatilis.

PMID- 15560222
TI  - Effect of pH on temperature stability of folates.

PMID- 15560223
TI  - Characterization of a Pyricularia grisea population from Uruguay by molecular
      analysis.

PMID- 15560224
TI  - Genetic diversity of the rice sheath blight pathogen population in India.

PMID- 15560225
TI  - Effect of supplemental magnesium, tryptophan, vitamin C and vitamin E on pigs'
      stress responses to vibration.

PMID- 15560226
TI  - Transcription regulation in Sulfolobus solfataricus: dissection of a higher order
      nucleoprotein complex.

PMID- 15560227
TI  - Thermal and high pressure inactivation of lipoxygenase in tomato juice.

PMID- 15560228
TI  - Microbiological and physiological processes affecting odor quality of
      strawberries during storage.

PMID- 15560229
TI  - Thermostability of Victoria grape (Vitis vinifera ssp. sativa) polyphenoloxidase.

PMID- 15560230
TI  - Integrated numerical spray model and event-driven Monte Carlo model of the
      fluidised bed coating process.

PMID- 15560231
TI  - Effects of drought stress induced by PEG 6000 on leaf water status of one
      domestic (Amygdalus dulcis) and two wild almond (A. lycioides and A. scoparia)
      species.

PMID- 15560232
TI  - Heat-induced changes in thiol availability of beta-lactoglobulin.

PMID- 15560233
TI  - CO2 efflux rates and xylem sap CO2 concentrations in detached branch segments of
      a young tree in relation to artificial sap flow.

PMID- 15560234
TI  - Evaluation of chemical changes during germination of lupin seeds.

PMID- 15560235
TI  - Analysis of antioxidant phytochemicals from Brussels sprout.

PMID- 15560236
TI  - Effect of preheating on the activity of carrot pectinmethylesterase and on the
      kinetics of degree of methylesterification of carrot pectin.

PMID- 15560237
TI  - Innovative waste treatment technologies.

PMID- 15560238
TI  - Applicability of the linear Arrhenius-Davey model to the modelling of the effect
      of water activty and temperature on the radial growth of Fusarium proliferatum
      and F. moniliforme.

PMID- 15560239
TI  - Spatial variability of throughfall water under beech (Fagus sylvatica L.).

PMID- 15560240
TI  - Interactions between diet composition and genotype of broiler chickens.

PMID- 15560241
TI  - Modelling of three dimensional air temperature distributions in porous media.

PMID- 15560242
TI  - Modelling evaporative cooling in greenhouses under central Mexican conditions.

PMID- 15560243
TI  - Influence of pectin conversions combined with high pressure shift freezing on the
      texture of frozen carrots.

PMID- 15560244
TI  - The evaluation of uncertainty propagation into river water quality predictions to
      guide future monitoring campaigns.

PMID- 15560245
TI  - Differences in proteolytic enzyme activities during growth of the pig with
      different IGF-II genotypes.

PMID- 15560246
TI  - Modelling ammonia volatilisation associated with liquid manure application.

PMID- 15560247
TI  - Effect of pressure pre-treatment on the sensitivity of egg white proteins to
      enzymatic hydrolysis: a kinetic study.

PMID- 15560248
TI  - Stability and activity of purified Sinapis alba myrosinase during temperature
      pressure treatments.

PMID- 15560249
TI  - Use of milk fatty acids in relation to milk production.

PMID- 15560250
TI  - Parameter sensitivity analysis of the FORUG model using the Monte Carlo
      simulation technique.

PMID- 15560251
TI  - ACE inhibitory activity from insects after enzymatic hydrolysis.

PMID- 15560252
TI  - Influence of the design and operational parameters on performance criteria of a
      flow injection analysis biosensor.

PMID- 15560253
TI  - Co-culture experiments between protective cultures and spoilage organisms on
      vacuum packaged cooked ham.

PMID- 15560254
TI  - Estimating European forest evapo transpiration by processing NOAA/AVHRR and
      METEOSAT imagery.

PMID- 15560255
TI  - Odd and branched chain fatty acids in rumen contents and milk of dairy cows fed
      forages from semi-natural grasslands.

PMID- 15560256
TI  - Origin of starch in dairy concentrates provokes differences in milk fatty acids
      related to lifestyle diseases.

PMID- 15560257
TI  - Rainwater harvesting and utilization in the loess plateau of China.

PMID- 15560258
TI  - Repression of Clostridium population in young broiler chickens after
      administration of a probiotic mixture.
AB  - The influence of the administration of a mixed probiotic on zootechnical
      performances and the microbial composition of the feces of young broilers, up 42
      days old, was investigated. In a six weeks trial the feed was supplemented with
      1(w/w)% of a mixture of five potentially probiotic strains belonging to the
      genera Lactobacillus and Enterococcus. No effect on the weight of the broilers
      was observed. Plate counting of fecal samples showed a decrease in the
      Clostridium population with more than 4 10log units after 5 days and 2 10log
      units after 14 days of treatment. The DGGE pattern obtained after nested PCR,
      revealed a significant shift in the Lactobacillus population. This study shows
      that the application of probiotics in the feed of broiler chickens considerably
      lowers the Clostridium population in broilers, hereby also lowering the risk of
      spreading in the housing through fecal contamination.

PMID- 15560259
TI  - The hemolymph of caterpillars Spodoptera littoralis: physico-chemical properties
      and ionic composition compared to culture media.
AB  - In this paper, we determined some physico-chemical properties like osmotic
      pressure, pH and electrical conductivity of the hemolymph from caterpillars of
      Spodoptera littoralis (Lepidoptera: Noctuidae) during the last larval instar. It
      was of interest that we observed an increase in osmotic pressure with the
      increase in age in the last instar that may concur with the start of histolysis
      at metamorphosis. These physicochemical properties were then compared to those of
      Grace's and modified Grace's tissue culture medium. In addition, concentrations
      of the cations Na, K, Ca and Mg, and the anions Cl, NO3, PO4 and SO4 were
      determined in the insect hemolymph of S. littoralis. The cations K and Mg reached
      high values with a percent of about 52% of the total amount of cations. The
      concentration of sodium was low. The total sum of the anions consisted about 56
      meq/1, and this allows to neutralise about 45 % of the total cations.

PMID- 15560260
TI  - Induction of cytoplasmic mannose-binding jacalin-related lectins is a common
      phenomenon in cereals treated with jasmonate methyl ester.
AB  - Treatment of whole plants with jasmonic acid methyl ester induces lectin activity
      in leaves of Oryza sativa, Hordeum vulgare, Triticum vulgare, Secale cereale and
      Zea mays. Purification and characterization of the lectins revealed that they all
      have a very similar molecular structure and carbohydrate-binding properties.
      Further analysis of the cDNA clones encoding the lectins revealed that they all
      belong to the family of cytoplasmic mannose-specific jacalin-related lectins.

PMID- 15560261
TI  - Quantitative measurement of spatial forest patterns in Flanders.
AB  - Worldwide, scientists and policy-makers emphasize the importance of planning and
      managing forests for multiple goals. Forests are considered as one of the
      elements of a landscape. When forests are to be managed at a landscape scale,
      there is a need for methodologies that describe these forested landscapes
      quantitatively. In the field of landscape ecology, a comprehensive list of
      descriptive variables is available for this aim. The selection of relevant
      variables is therefore important. This paper analyses the forest cover pattern of
      Flanders. Using multivariate techniques, a set of variables is selected.

PMID- 15560262
TI  - The quantitative and qualitative difference between a F1 hybrid of maize and its
      F2 generation.
AB  - The majority of modern maize varieties are single F1 hybrids. The yield
      performance of the F2 generation is known to be inferior to the F1 yield
      performance. We crossed several F1 hybrids and compared these crossings, together
      with true F2 generations, with the original F1s. Compared to the F1 generation,
      biomass yield in the F2 generation dropped with -26.7%, and with -8.7% in the
      crossings. Ear yield dropped with -35.3% and -10.7% respectively. F2 generations
      had a reduced early vigour and the ear filling startedlater. The yield of some F1
      diallel crosses was not significantly different from the yield of the parental
      F1s.

PMID- 15560263
TI  - Vegetation development and floristical diversity of newly created sown and unsown
      field margin strips on ex arable land during the first 3 successional years.
AB  - Early succesion of newly created sown/unsown margin strips on ex arableland,
      managed by two cuttings per year with/without removal of cuttings was
      characterised by the replacement of annuals in favour of perennials, a steadily
      increase in the importance of monocots and a decrease in non N-fixing dicots.
      Mowing with removal of cuttings delayed this succession pattern. Sorenson's
      qualitative similarity index (based solely on species occurrence) revealed that
      species composition of the sown communities (in terms of species occurrence)
      became increasingly similar to the unsown plots. Furthermore convergence in
      vegetation composition between sown and unsown plots occurred also in terms of
      species importance as assessed by Sorenson's quantitative index (based on the
      combination of species occurrence and importance). Similarity in species
      importance (but not of species occurrence) was significantly enhanced by cutting
      with removal of cuttings. During the first 3 successional years, species
      diversity of sown and unsown communities converged in time, irrespective of
      mowing regime or location. The decrease in species diversity, number of sown
      wildflower species and wildflower density of sown communities was more pronounced
      under a mowing regime without removal of cuttings. The annual addition of mown
      roadside herbage significantly enhanced species richness but not the importance
      of dicots.

PMID- 15560264
TI  - Radicals and antioxidants in relation to human and animal health: a case for
      functional feeding.

PMID- 15560265
TI  - Effects of freezing and drying grass products prior to fatty acid extraction on
      grass fatty acid and lipid class composition--a technical note.
AB  - Grass and grass silage represent a rich and natural source of omega-3
      polyunsaturated fatty acids, in particular linolenic acid, for ruminants. Recent
      research, focusing on improving the content of these beneficial fatty acids in
      grass, requires storage of the forage samples prior to analysis. In this study,
      we evaluated whether conservation of fresh grass and grass silage by freezing (1
      and 4 weeks,--18 degrees C) and/or drying (24h, 50 degrees C) affected its fatty
      acid content and induced shifts between lipid classes. FA were extracted using
      chloroform/methanol (2/1, v/v) and triacylglycerols (TAG), free fatty acids (FFA)
      and polar lipids (PL) were separated by thin layer chromatography. Fatty methyl
      esters (FAME) were identified by gas chromatography. Loss of thawing liquor might
      provoke a dramatic decrease in extractable lipid after frozen storage of both
      grass and grass silage. Morever, after frozen storage, fatty acids in grass but
      not in grass silage seem subjected to a higher rate o f lipolysis and oxidation,
      as suggested by increased quantities of FFA (3.1, 7.6, 8.4 % of total FAME) and
      reduced proportions of poly-unsaturated fatty acids (79.5, 73.6 and 74.1 % of
      total FAME) when analysing fresh grass samples directly or after 1 and 4 weeks of
      frozen storage, respectively. Drying of fresh grass did not provoke changes in FA
      composition, but distribution of FA over lipid classes was significantly altered,
      with an increase in TAG (5.1 to 17.9 % of total FAME) and FFA (2.4 to 14.9 % of
      total FAME) and lower proportions of PL (90.7 to 55.7 % of total FAME).

PMID- 15560266
TI  - Nutritive value and qualitative assessment of secondary compounds in seeds of
      eight tropical browse, shrub and pulse legumes.
AB  - Seeds of four tropical multipurpose trees (Albizia saman, Albizia lebbeck,
      Albizia rhizonse, Leucaena leucocephala), two shrubs (Tephrosia candida,
      Tephrosia bracteolata) and two pulse legume (Lablab purpureus, Canavalia
      ensiformis) were chemically analysed for dry matter (DM), ash, crude protein
      (CP), neutral detergent fibre (NDF) and ether extract (EE). Qualitative
      evaluation of secondary metabolites (saponins, phenols, steroids, and alkaloids)
      was elucidated. The DM, ash, CP, NDF and EE ranged between 88.9-93.6 %, 3.0-5.4
      %, 24.8-38.2 %, 22.1-46.9 % and 2.0-17.0 % respectively. All seed species
      contained at least one group of secondary plant metabolites and steroids were
      common to all except C. ensiformis that was not implicated for any. A. lebbeck
      and A. rhizonse showed low saponin content. Indications for water soluble tannins
      were reported for L. leucocephala while the two species of Tephrosia contained
      flavonoids or condensed tannins. The study suggested the potentials of the
      legumes seed species as a feed source for ruminants.

PMID- 15560267
TI  - [Urologic work and biography of Prof. Rafael Alcala Santaella (1896-1959).
      Historical document analysis].
AB  - OBJECTIVES: We find that Urology at the end of the 20th century was a
      consolidated speciality as a result of years of evolution and development, and
      the studies and works of authors whose contributions are considered today the
      basements of our speciality. So we think that Urology should be understood with
      its historical references, because, as Aristotle said "... thinks are better
      understood when one has got to clearly see how they were formed..." Numerous
      specialists contributed to this; among them we can cite Prof. Rafael Alcala
      Santaella, the object of this bibliographic and scientific works compilation
      paper. METHODS: We reviewed all his scientific works. Original articles have been
      obtained from Medicina Ibera, Revista Espanola de Cirugia y Urologia, and
      Cirugia, Urologia y Ginecologia. His most important urologic work is Clinic
      Urology (1942), divided in 3 volumes. For his biography we used the biographic
      and bibliographic historical source of Spanish urology over the 20th-century and
      direct family members interviews. RESULTS: He analyzed topics as important as
      voiding disorders and the study of urine pyuria. He gave special importance to
      the study of prostatic pathology, its diagnosis by means of cystourethrography,
      and the modification of surgical techniques, as well as the results of urinary
      diversions performed in his department. CONCLUSIONS: Due to his extensive
      scientific and technical contributions he is one of the most outstanding figures
      of Valencia's Urology over the first half of the 20th century, together with
      Rafael Molla Rodrigo and Nicasio Benlloch Giner.

PMID- 15560268
TI  - [Asymptomatic bacteriuria in women. Epidemiological, pathologic and therapeutic
      study].
AB  - OBJECTIVES: To perform an epidemiological, pathologic and therapeutic study of
      asymptomatic bacteriuria (AB) in a population of outpatient women. METHODS:
      Transversal study for detection of AB in 1718 outpatient women 14-year-old or
      older. All patients complied with the inclusion/exclusion criteria for the study.
      Two groups of patients, with AB (n = 113) and controls without AB (n = 200),
      underwent: 1) urine analysis: urine sediment, biochemical analysis, and culture;
      2) blood tests: hemoglobin, red blood cell count, urea, creatinine, sedimentation
      rate velocity, C reactive protein, immunoglobulins (IgA, IgM, and IgG), HLA-A3,
      blood group and Rh. The therapeutic management for AB was analyzed. Comparative
      statistical analyses of data were performed. RESULTS: AB prevalence was 6.34%.
      The most frequently isolated germ was E. coli (77.87%). Diabetes mellitus was
      detected in 27.43% of patients with AB and 7.01% without AB (27.43% vs. 7.01%);
      coronary arterial disease and other heart disorders (9.73% vs. 4%, p = 0.0206);
      general cardiovascular disorders excluding hypertension (46.9% vs. 31%, p =
      0.0025). Urine analysis showed leukocyturia in 81.41% of the patients with AB and
      17.5% without AB (p = 0.0002); positive nitrites (77.87% vs. 0%, p < 0.001);
      urine sediment showed bacteriuria in 86.72% of patients with AB and 0% of non-AB
      patients (p < 0.0001), leukocytes (93.80% vs. 6%, p < 0.0001), and pyuria (19.46%
      vs. 2.5%). Low water intake (50.44% vs. 9.5%, p < 0.0001) was the most
      significant urinary tract infection hygienic-dietetic predisposing factor. Higher
      levels of IgA (15% vs. 2%, p = 0.004). Positive HLA-A 3 (5% vs. 0%, p = 0.039),
      Rh negative (16.66% vs. 13.33%), and increased C reactive protein (15% vs. 10%).
      Renal abnormalities detected by radiological tests (10.29% vs. 1.47%, p = 0.014).
      AB disappeared after treatment with cefuroxime, ceftibuten,
      trimetropin/sulfametoxazole and amoxicillin in 100% of the patients receiving
      treatment. Topical vaginal estrogen therapy was effective in 38.09% of the
      patients. CONCLUSIONS: The prevalence of AB increases with age. The most frequent
      germ is Escherichia coli. A statistically significant greater number of coronary
      artery disease, other heart diseases, and cardiovascular disorders were found
      among patients with AB in comparison with non-AB controls. Immunoglobulins levels
      disturbances, and HLA-A3 positivity suggest an immune systemic imbalance in
      certain patients with recurrent AB. Other therapeutic alternatives such as
      vaginal topical estrogens, fruit juices intake, vaccinations, etc. should be
      pursued in addition to antimicrobial therapy.

PMID- 15560269
TI  - [Prognostic factors of prostate cancer: usefulness of Ki-67 expression in
      preoperative biopsies].
AB  - OBJECTIVES: To evaluate the usefulness of Ki-67 expression in preoperative
      diagnostic biopsies to predict prostate cancer biochemical relapse after radical
      prostatectomy. METHODS: We analyze the expression of Ki-67 in ultrasound guided
      biopsies of 103 patients who underwent radical prostatectomy. Mean follow-up was
      3.4 years (1.3-8.8 yr.). We correlated biochemical progression with traditional
      prognostic factors such as PSA (> 10/< or = 10), Gleason (> or = 7/< 7), pT
      classification (pT3/pT 0-2), and the immunohistochemical prognostic factor Ki-67
      (> 3%/< or = 3%). RESULTS: 71/103 (69%) patients did not have progression and 32
      (31%) had biochemical progression. Mean preoperative PSA was 10.7 ng/ml in
      patients without progression and 20.90 ng/ml in patients with biochemical
      progression (p = 0.0001). Mean Gleason score was 6.03 in patients without
      progression and 6.75 in patients with biochemical progression (p = 0.0001). Ki-67
      expression was 3.95% in patients without progression in comparison to 5.05% of
      patients with biochemical progression. 12/67 (17.9%) of pT 0-2 tumors and 20/36
      (55.6%) pT3 tumors progressed (p = 0.0001). Multivariate analysis indicates that
      there is not relationship between Ki-67 (> 3% < or = 3%) in preoperative biopsy
      specimens and prostate cancer biochemical progression after radical prostatectomy
      (p = 0.204). CONCLUSIONS: The immunohistochemical prognostic factor Ki-67 (> 3%/<
      or = 3%) in preoperative biopsies is less effective than classic factors, PSA (>
      10/< or = 10), Gleason score (> or = 7/< 7) and pT classification (pT3/pT 0-2),
      to predict prostate cancer biochemical progression after radical prostatectomy.

PMID- 15560270
TI  - [Epidemiological trends in prostate cancer over the last years].
AB  - OBJECTIVES: To analyze the evolution of prostate cancer (PCa) in our community
      health area over the last years, in terms of incidence, clinical-epidemiological
      characteristics, and cancer-specific mortality. METHODS: Retrospective analysis
      of the medical records of patients with PCa in our hospital over the 1991-2003
      period. We calculated the annual incidence rates for our community health area as
      well as its trend over the period of study. Changes of several clinical
      epidemiological parameters over time were studied. The evolution of PCa mortality
      was also analyzed. RESULTS: 730 patients with PCa were evaluated. Median age and
      PSA at diagnosis were 69 years and 11.4 ng/ml, respectively. 60.5% tumors were
      detected in a localized clinical stage, and 18.6% were metastasic. 30.4% of PCa
      in the study (the most numerous group) had a Gleason score between 5 and 6. A
      constant increase of PCa incidence was observed with an annual percentage
      increase of 5.5% (p < 0.001). Standardized incidence rate for the year 2003
      Spanish population pyramid was 100.9 cases/100,000 males. A significant trend to
      a greater proportion of PCa cases diagnosed by uncontrolled screening was
      observed, being the cases currently detected after symptoms only a small
      proportion (p < 0.001). Decreases in the age at diagnosis (p < 0.001), PSA level
      (p < 0.001), proportion of advanced clinical stages (p < 0.001), as well as
      proportion of cancers with well-differentiated Gleason score (2-4) (p < 0.001)
      were also detected. PCa mortality adjusted by the population pyramid was 8.7
      deaths/100,000 males in the year 2003. CONCLUSIONS: We found an increase in the
      incidence of prostate cancer in our community health area over the last years,
      parallel to an increase in the proportion of cases detected by screening in
      asymptomatic population. Because of that, tumors currently detected tend to
      appear in younger ages, with lower PSA levels, and localized clinical stages.

PMID- 15560271
TI  - [Bladder leiomyoma in a male patient].
AB  - OBJECTIVES: Bladder leiomyoma is an uncommon mesenchymal benign tumor. It is
      generally asymptomatic and incidentally detected. METHODS: We report a new case
      managed with transurethral resection without evidence of relapse. A bibliographic
      search was performed to evaluate the diagnostic techniques, clinical features and
      treatment options of this rare disease. CONCLUSIONS: Bladder leiomyoma is a
      benign mesenchymal tumor originating from smooth muscle. Biopsy and histological
      study are required for definitive diagnosis. Surgery is the treatment of choice,
      and it has an excellent prognosis if resection is complete.

PMID- 15560272
TI  - [Hand-assisted laparoscopic radical nephrectomy vs. open nephrectomy in the
      treatment of clinically localized renal cell carcinoma. Comparative study].
AB  - INTRODUCTION: The description of the first laparoscopic nephrectomy made a
      revolution in the managing of the benign and malignant renal diseases. Hand
      assisted laparoscopy (HAL) was developed with the aim of offering advantages to
      both patients and surgeons. The aim of the present work is to compare, in our
      experience, the results offered in the radical nephrectomy by HAL and open
      surgery, by analysis of surgical time, estimated blood loss during surgery and
      hospital stay. METHODS: Eleven Hand-assisted laparoscopic (HAL) radical
      nephrectomies and eight open radical nephrectomies were carried out at our
      institution during the same period (June 2001 to December 2002). All patients
      underwent computed tomography and were found to have a clinically localised
      functioning renal mass in all cases. The size of this renal mass was 4-7 cm
      (average 5.5 cm) in the HAL group and 4.5-15 cm (average 7.8 cm) in the open
      group. Patient age, body mass index, and American Society of Anaesthesiologists'
      score showed no significant difference between groups. RESULTS: The average
      surgical time in the HAL group was 156.72 minutes, the average blood loss during
      surgery was of 83.6 ml and the average hospital stay was of 3.09 days. Conversion
      to open surgery was not necessary in any patient. Average surgical time in the
      open surgery group was 178.25 minutes, the estimated blood loss during surgery
      was of 337.75 ml (p < 0.05) and the hospital stay was of 5.37 days (p < 0.05).
      The comparison of the means by two-tailed student's t test revealed significant
      differences in estimated blood loss and hospital stay, favoring HAL, and no
      significant differences in surgical time. CONCLUSIONS: HAL nephrectomy is
      feasible in almost all nephrectomies and is a safe, reproducible, and minimally
      invasive technique to perform extirpable renal surgery. HAL offer clear
      advantages over traditional open surgery, including decreased blood loss and
      hospital stay.

PMID- 15560273
TI  - [Retroperitoneal paraganglioma].
AB  - OBJECTIVES: To report the radiological findings of retroperitoneal
      paragangliomas. METHODS: A patient who presents with colic pain and undergoes
      intravenous urography and CT scan. RESULTS: KUB x-ray revealed an increase of
      radiodensity on the left flank. The urography showed a partially obstructive
      urinary lithiasis in the proximal third of the left ureter with a mass effect
      laterally displacing pelvis and ureter. The study was completed with an i.v.
      contrast abdominal CT scan which showed a left para-aortic solid mass under the
      kidney with heterogeneous contrast uptake. CONCLUSIONS: The correlation of
      symptoms and catecholamine levels is the best way to guide the etiological
      diagnosis after CT scan.

PMID- 15560274
TI  - [Penile metastasis of a prostatic adenocarcinoma].
AB  - OBJECTIVES: To report one case of prostate carcinoma with metastasis to the
      corpora cavernosum. METHODS: We report the case of a 79-year-old patient with the
      diagnosis of Gleason 9 prostatic adenocarcinoma who presented a hard lesion on
      the glans penis one year after starting androgen blockade. The patient underwent
      palliative TURP and biopsy of the lesion. RESULTS: Pathology reported a penile
      metastasis of prostatic adenocarcinoma. CONCLUSIONS: Penile metastasis are rare,
      usually appearing in advanced stages of the primary disease; their treatment is
      palliative and should only be carried out in symptomatic patients.

PMID- 15560275
TI  - [Bilateral laparoscopic nephrectomy for renal cancer].
AB  - OBJECTIVES: To report the case of a patient with a bilateral synchronic renal
      tumor who underwent a laparoscopic surgical approach. METHODS: 57-year-old
      caucasian male with history of end stage renal disease and secondary
      hypertension, type II diabetes Mellitus, proteinuria of 2.83 g/24 hours, chronic
      smoker, and allergic to iodinated contrast who underwent right nephrectomy and
      simultaneous left laparoscopic transperitoneal nephroureterectomy for a bilateral
      renal tumor. RESULTS: Operative time was 4 hours; NG tube was inserted; estimated
      blood loss was 200 ml and no transfusions were required. Oral intake was re
      established after two days. No intraoperative complications occurred; metabolic
      acidosis appearing in the intermediate postoperative period was corrected with
      intravenous sodium bicarbonate. Hospital stay was 9 days. CONCLUSIONS: Bilateral
      laparoscopic nephrectomy is an effective therapeutic option in the management of
      patients with bilateral malignant renal diseases, which ensures surgical
      radicality, and diminishes morbidity, hospital stay and recovery time.

PMID- 15560276
TI  - [Giant bizarre scrotal leiomyoma].
AB  - OBJECTIVES: To review the diagnosis and therapeutic management of scrotal wall
      smooth muscle tumors by reporting an illustrative case. To emphasize that despite
      their histological characteristics on presentation, compatible with malignancy,
      these tumors have a benign behaviour, even when their size is much bigger than
      the ones found in the review bibliography. METHODS: 75-year-old male who
      presented a big, very slowly growing, painless, mobile, hard, not adhered to deep
      layers, non transilluminating scrotal tumor. RESULTS: Pathology reported a giant
      bizarre scrotal leiomyoma. CONCLUSIONS: We emphasize the atypical characteristics
      of this case, which despite its compliance with almost all classical criteria
      establishing the malignant character of tumor lesions has a benign behaviour. It
      complies with the criterion that, accordingly to reviewed bibliography, seems to
      be the most important to determine it: the absence of mitosis. We also insist on
      the importance of an adequate diagnostic approach which guarantees a proper
      surgical approach, for which we think ultrasound is essential.

PMID- 15560277
TI  - [Urinary stone in a Bricker's ileal conduit].
AB  - OBJECTIVES: To report one case of urinary stone as a relatively frequent
      complications of urinary diversion using bowel loops. METHODS: We perform a short
      bibliographic review using the case report format. RESULTS: Stone formation in
      Bricker's type urinary diversion is secondary to various factors such as urinary
      stasis, bacteriuria, presence of intestinal mucus, metallic sutures, metabolic
      disturbances, etc. CONCLUSIONS: Periodic control by radiological studies is
      recommended due to the high frequency of this complication in patients with
      urinary diversion. Treatment is usually conservative or minimally invasive, being
      surgery reserved for those cases in which stone extraction is not safe using
      other methods.

PMID- 15560278
TI  - [Infiltrative small cell carcinoma of the bladder. New case report: treatment
      with radical surgery and chemotherapy].
AB  - OBJECTIVES: To report a new case of infiltrative small cell bladder cancer.
      METHODS: We describe the case of a 60-year-old male patient who consulted for
      monosymptomatic hematuria over a few weeks. Cystoscopy showed a neoplasia in the
      anterior wall of the bladder. Pathological analysis of the TUR chips was
      compatible with infiltrative small cell tumor. After a negative staging study
      radical cystectomy plus adjuvant chemotherapy were indicated. RESULTS:
      Pathological study of the surgical specimen confirmed the diagnosis with
      involvement of the surrounding fat. There is no evidence of neoplasic involvement
      after 24 months follow-up. CONCLUSIONS: We point out the validity of a radical
      surgical approach for this tumor, also emphasizing the importance of adjuvant
      chemotherapy. We concur with other authors in the need of multicentric studies to
      outline the most effective surgical option, due to the limited number of cases of
      this entity.

PMID- 15560279
TI  - [True hermaphroditism].
AB  - OBJECTIVES: To report the case of a 23-year-old patient with ambiguous external
      genitalia, gynecomastia and cyclic hematuria who demanded proper investigations
      and actions to be considered male. METHODS: A set of tests were performed:
      history and physical examination, blood tests, hormonal determinations, nuclear
      chromatin, cariotype, renal and pelvic ultrasound, voiding cystourethrogram
      (VCUG), laparoscopy, exploratory laparotomy, left hystero-salpingo-oophorectomy,
      right orchydopexy, testicular biopsy and fibrous cord section. RESULTS: History
      and physical examination showed a long slim individual with male fat
      distribution, female pubic hair distribution, Tanner's grade 4 gynecomastia with
      scarce breast hair, absence of scrotal gonads, and urogenital sinus. Blood tests
      were normal. Hormonal tests were normal. There were no anomalies in the renal
      ultrasound and a small uterus was found in the pelvic ultrasound. The chromatin
      test was positive and cariotype showed a 46/XX cell line. The VCUG only
      contrasted a normal posterior urethra. Laparotomy discovered a small uterus with
      two fallopian tubes: the left one was dilated with a polycystic ovary, and the
      right one was hypoplastic with testicle, vas deferens, and epididymis near it.
      Right orchydopexy was carried out after biopsy and section of the fibrous cord.
      Androgen therapy, subcutaneous mastectomy, and urethroplasty were performed
      postoperatively with satisfactory results. CONCLUSIONS: Severe cases of genital
      anomalies may be solved after a good psychological evaluation and proper surgical
      repair.

PMID- 15560280
TI  - [Precocious puberty in a 6-year-old boy with bilateral cryptorchidism].
AB  - OBJECTIVES: To report one case of precocious puberty in a 6-year-old boy with
      bilateral cryptorchidism. METHODS: History and physical examination, blood tests,
      nuclear chromatin and cariotype, bone age, pneumopelvis, hormonal tests,
      laparotomy and hysterectomy were performed. RESULTS: The absence of testicles
      within the scrotum was proved, chromatin was positive and cariotype was normal
      female 46/XX. Bone age was accelerated. The pneumopelvis showed a uterine shadow
      and two gonadal shadows in both sides. Urinary 17-ketosteroids and pregnanetriol
      were elevated. Due to the male sex identification, it was decided to reinforce
      the generic role before starting hormone treatment. Hysterectomy and substitutive
      steroid treatment were undertaken. CONCLUSIONS: Genital ambiguity should be
      considered when evaluating a boy without palpable gonads.

PMID- 15560281
TI  - ["Encrustating cystitis"].

PMID- 15560282
TI  - Spontaneous rupture of renal leiomyosarcoma in a 45-year-old woman.
AB  - OBJECTIVES: Leiomyosarcoma is a rare histological subtype of renal sarcomas,
      accounting for approximately 50-60% of the reported cases. Spontaneous rupture of
      renal tumor is an uncommon event and the most frequent cause is angiomyolipoma.
      We report a case of spontaneous rupture of leiomyosarcoma in a 45-year-old woman,
      presenting with severe left flank pain and perirenal hemorrhage. METHODS: A 45
      year-old caucasian white woman was transferred to our department from emergency
      room of a different Hospital for acute left flank pain interpreted as a renal
      colic not responsive to medical therapy. On clinical examination patient was
      haemodynamically stable but with rapid decrease in hemoglobin, pale, without
      haematuria with a persistent left flank and hypochondrium pain as in acute
      abdomen. CT scan of abdomen showed a retroperitoneal haematoma around the left
      kidney, and a large heterogeneous mass. RESULTS: Laparotomy was urgently
      performed. There was large retroperitoneal hematoma extending from left kidney to
      pelvic space. At the upper pole of the kidney a bleeding tumor was found. Radical
      nephrectomy was performed. The histological diagnosis was of low-grade
      leiomyosarcoma from renal angiomyolipoma. CONCLUSIONS: We attract attention both
      on kidney cancer (at our knowledge only 3 cases described in literature) and on
      the need of imaging in the clinical approach of renal colic. We strongly believe
      that the patients presenting at emergency for renal colic must be scanned by
      ultrasounds or TC.

PMID- 15560283
TI  - [Health education as prevention of alcoholism in young people].
AB  - The close correlation between road accidents and excessive consumption of
      alcoholic beverages, as well as the lowering of the minimal age for alcohol
      drinking, prompted the Authors to examine the acute and chronic effects of
      alcohol on the human organism; therefore, they analyze the metabolic effects of
      alcohol and, after having described it's few beneficial effects, they furnish
      some suggestions to avoid above all "the havoc of Saturday evening", outlining in
      detail the causes and progressive states of alcoholic intoxication. The Authors,
      in agreement with the current views of prevention, professed by the scientific
      community, emphasize information and health education as the main tools that
      guarantee primary prevention in young people who, as it is well-known, belong to
      the most vulnerable segments of the population. To such purpose they created a
      poster, to which a CD will follow, that could be distributed and discussed in
      schools with the purpose to encourage social debate and constructive involvement
      of students, teachers and their parents.

PMID- 15560284
TI  - [The new frontier of distance learning: the climate of the virtual lecture hall].
AB  - INTRODUCTION: The recent ECM standards outline new dilemmas not only under an
      economic and/or management point of view, but even under a teaching and
      procedural aspect. FAD seems to solve problems, allowing us to arrange courses
      according to our demand, but it still doesn't solve all the issues, for example,
      the teaching-learning model. PROBLEM ANALYSIS: The article starts analysing
      formative procedures to reflect in an interactive logic about object and subject
      in FAD, to set a dynamic learning process in a knowledge management viewpoint,
      where the user is fully aware that he/she will be divided from his/her tutor and
      from his/her colleagues in the virtual classroom. The learning environment is a
      crucial circumstance to assure full functionality of the course and to make the
      FAD experience a valuable one and repeatable in the future for different courses.
      CONCLUSIONS: FAD is an asynchronous activity and for this it could be moulded
      according to the single user's requirements. It needs a relational dimension to
      facilitate the learning process through the strategy sharing of problem solving.

PMID- 15560285
TI  - [Sodium channels and multiple sclerosis].
AB  - Multiple Sclerosis is a chronic demyelinating disease of the central nervous
      system of undetermined etiology. Damage of myelinated fibers leads to block of
      conduction of impulses. In myelinated axons sodium channels are expressed at high
      density and they play a very important role in the conduction of nervous impulse.
      In myelinated fibers affected by Multiple Sclerosis substantial variations of
      sodium channels pattern occurs. These variations can help to explain
      pathophysiological and clinical aspects of Multiple Sclerosis and open a new way
      to approach and, probably, treat this disease.

PMID- 15560286
TI  - [Prognostic factors in functional outcome after stroke: a review].
AB  - Survivors of stroke constitute the largest group of patients receiving
      rehabilitative therapy. Purpose of this article is to review the prognostic
      factors which can affect functional outcome after stroke. An accurate prognostic
      assessment is fundamental after cerebrovascular accident, in order to plan the
      rehabilitative project and define both early and long-term objectives. We found
      agreement of opinions about the prognostic value of some factors, whereas three
      are difference of opinions about other prognostic factors in predicting
      neurological outcome.

PMID- 15560287
TI  - [Russell's syndrome: a case of long-term survival and review of the literature].
AB  - We report the case of a two years old, normally eating child, affected by organic
      macies and severe dystrophy. After the negative response of blood and laboratory
      examinations let us exclude a malabsorption syndrome, only the performance of
      neuro-radiologic exams showed evidence of a subthalamic tumor as the cause of a
      "Diencephalic syndrome". Diencephalic syndrome or Russell's syndrome is a
      diencephalic tumor induced disease, which sets in the first time of life. The
      disease clinical markers are a severe emaciation with appetite preservation and
      absence or very scarce evidence of any telltale neurological sign. The tumoral
      histo-pathology most frequently shows a low grade of malignancy astrocytoma,
      whose eradication is very often difficult because of particular anatomic site.
      Treatment of choice includes an excisional biopsy with chemotherapy and
      radiotherapy. We report a clinical case of long-term survival and review of the
      literature.

PMID- 15560288
TI  - [Proceduralism and bioethics (II)].

PMID- 15560289
TI  - [Malnutrition detected by "bioelectrical status" of total and segmental body mass
      to nutritional management of patients].
AB  - We examined 182 controls with Body Mass Index (BMI) between 20 and 25 kg/m2 and
      246 hospitalised patients divided into 3 groups: the first one consisted of 70
      severe malnourished with (BMI) < 20 kg/m2, the second one of 43 light
      malnourished with BMI between 20 and 25 kg/m2 and the last one of 133 obese with
      BMI > 25 kg/m2. The Resistance (Rs) and Reactance (Xc), with the Phase angle
      ((phi), are detected from total and segmental (Arm and "Trunk + Leg") body. We
      analysed electric parameters plotting them on 4 different graphs which reported
      the values of: 1) total Rs vs total Xc; 2) segmental Rs vs segmental Xc; 3) total
      Rs/height vs weight/ height; 4) total Xc/height vs weight/height. Rs and Xc were
      different in all groups: the severe malnourished patients (1st group) gave
      evidence of a paradoxical increase of Rs and a decrease of phi. The mean values
      decreased for the patient of the 2nd and 3rd group (the (phi reduced especially
      for the 2nd group). Referring to the segmental measures, "Trunk + Leg" biases
      total Rs and Xc much more than Arm. In addition the phi of "Trunk + Leg" is more
      similar to the total o than the Arm one. If compared with the total, this last
      one highly decreases in the patients of the 1st and 2nd group. We conclude that
      segmental bioelectrical values (Rs, Xc, phi) integrate the total one, because
      they allow to find out the correlation between total parameters and a specific
      body segment. Total and segmental Rs, Xc (and phi) values and segmental phi ratio
      are related to the malnutrition. The approach together with the analysis of the
      Graphics result to a prompt inspection of the individual bioelectrical status in
      subjects.

PMID- 15560290
TI  - [Proteinuria].

PMID- 15560291
TI  - [Hereditary hemocromatosis].
AB  - Hereditary hemochromatosis is a disorder of iron metabolism characterized by a
      progressive tissue iron overload which leads to an irreversible organ damage if
      it is not treated timely. The recent developments in the field of molecular
      medicine have radically changed the physiopathology and the diagnosis of this
      disease. However, transferrin saturation and serum ferritin are still the most
      reliable tests for the detection of subjects with hereditary hemochromatosis.
      Therapeutic phlebotomy is the mainstay of the treatment of hereditary
      hemochromatosis. If phlebotomy is started before the onset of irreversible organ
      damages, the life expectancy of these patients is similar to that of normal
      population.

PMID- 15560292
TI  - [Limitation of access to an infectious disease ward due to lack of compatible
      hospital room. A four-year survey, and relevant observations].
AB  - A four-year retrospective survey was carried out at our Infectious Disease ward,
      to point out discrepancies between immediately hospitalized patients, and those
      referred to us for admission, but needing trasferral elsewhere, due to lack of a
      suitable room. Since the year 2000, 439 patients out of 1979 (28.5%) could not
      find a place at our ward. Paralleling increased rooms at our ward in June 2002
      (16 to 35 beds), the described phenomenon had a sharp drop, but a subsequent
      stabilization followed, with around 13% of Infectious Disease patients sent
      elsewhere for hospitalization until July 2003. Patients with severe,
      transmissible diseases are of particular concern, when the accepting Infectious
      Disease unit is located 40-115 km far from our city. This occurrence happened in
      nearly 25% of patients trasferred from our Hospital from the year 2000.

PMID- 15560293
TI  - [Continuing education in transfusional medicine. Analysis of results of
      evaluation of the formative events (2001-2003)].
AB  - The present study is comparing the evaluation cards of the event, related to all
      the events executed in the experimental phase (363 participants) with those ones
      achieved in the first and second year of running phase system (321 and 180
      participants), with particular reference to the emergent opinions about the five
      year compulsoriness of the attainment of the credits, imposed by the normative of
      the Ministry of Health. The analysis of the results underlines the discordance
      between the evaluations and the opinions expressed in the same ones. Finally, in
      the organization of a formative event is necessary to consider the not-measured
      factors that engrave on those measured ones (as the effectiveness). The
      effectiveness should also be measured at a distance of months, referring them to
      the possible applications of learned results on the working place, also
      considering the resistances to individual or collective change.

PMID- 15560294
TI  - [Chronic hepatitis C/autoimmune hepatitis overlap syndrome: report of two cases].
AB  - The coexistence of non-organ specific autoantibodies and chronic hepatitis C
      features raises the dilemma as to whether the pathogenesis is viral or autoimmune
      and consequently to be treated with interferon or corticosteroids. Two cases with
      autoimmune characteristics and chronic hepatitis C are reported. We discuss the
      possibility of classifying this overlap form in three distinct entities: viral
      disease with an autoimmune epiphenomenon ("false hepatitis C/autoimmune hepatitis
      overlap syndrome"), viral disease associated to an autoimmune pathogenic
      component ("true hepatitis C/autoimmune hepatitis overlap syndrome") and false
      serological anti-HCV positivity in classical autoimmune hepatitis. In our
      experience the interferon/corticosteroid association was successful.

PMID- 15560295
TI  - [Hypersensitivity reactions to chemotherapeutic antineoplastic agents].
AB  - Hypersensitivity reactions to chemotherapeutic antineoplastic agents represent a
      medical issue commonly considered of little importance. However, if in most
      courses of treatment the likelihood of an allergic reaction is very low, for some
      drugs, particularly L-asparaginase, taxans and platinum salts, the possible
      occurrence of hypersensitivity, not rarely clinically severe, with respiratory
      and cardiovascular involvement, may require the discontinuation of chemotherapy
      with obvious negative consequences for the patient. To prevent such event a
      number of measures are available, first represented by the change of the drug
      with similar molecules obtained by biotechnology (this is true for L
      asparaginase), or with another agent of the same class, though with caution
      especially with platinum salts because the possibility of an allergic reaction
      cannot be excluded. Preventive protocols mainly based on high dose
      corticosteroids and antihistamines are also available and, concerning taxans and
      platinum salts, desensitization may be successfully managed.

PMID- 15560296
TI  - [Importance of oral signs in the diagnosis of atypical forms of celiac disease].
AB  - The dramatic improvement in knowledge concerning celiac disease (CD) has
      disclosed the pattern of the associated clinical manifestations and the often
      atypical or silent presentation of this disease, which makes clinical diagnosis
      difficult. Also oral manifestations, mostly recurrent apthous stomatitis (RAS)
      and dental enamel hypoplasia, are atypical signs of CD. Our opinion about the
      possibility of performing mass-screening to reveal atypical or silent CD is in
      agreement whit who is asserting that a sistematical case-finding is, at present,
      the most suitable epidemiological approach. So, we think that patients affected
      by RAS, or dental enamel hypoplasia, should be considered, even in the absence of
      any gastrointestinal symptom, at-risk subjects, and should therefore undergo
      diagnostic procedure for CD.

PMID- 15560297
TI  - [S.A.PH.O. syndrome: a still little known clinical syndrome].
AB  - S.A.P.H.O. syndrome is characterized by the association, even not simultaneous,
      of osteoarticular and cutaneous manifestations. This review has the purpose to
      clear up some features of clinical manifestations and the osteo-articular
      involvement. Articular mainly feature is the involvement of anterior chest wall,
      that begins with slow evolving pain. Skin involvement is characterized by acne
      conglobata and pustolosis palmaris-plantaris. Instrumental investigations that
      fit better for studying the anterior chest wall, complex region, are bone
      scintigraphy, computed tomography and nuclear magnetic resonance, with their
      domain pattern. Symptomatic therapy are mostly represented by NSAIDs, but still
      opiate drugs can be prescribed; corticosteroids have variable and unforeseeable
      efficacy. Bisphosfonates are usually utilized due to their anti-osteoclastic
      effects. Finally, because of documented incremented production of TNFalpha,
      TNFalpha blocking agents should be effectively utilized.

PMID- 15560298
TI  - [Sleep apnea and cardiovascular diseases. A report of the National Center on
      Sleep Disorders Research (NCSDR) and the National Heart, Lung and Blood Institute
      (NHLBI)].

PMID- 15560299
TI  - [Total restorative proctocolectomy in the surgical treatment of ulcerative
      rectocolitis].

PMID- 15560300
TI  - [Endoscopic adrenalectomy: indications, techniques and outcome].

PMID- 15560301
TI  - [Traumatic lesions of the diaphragm].
AB  - The Authors studied 30 cases of diaphragmatic traumatisms from 1972 to 2003 to
      stress the difficulty to achieve an early diagnosis and the need of their
      immediate treatment: 26 of these patients were male and 4 female (6.5:1); the
      pathogenesis was in 50% of cases an open trauma and in 50% a closed trauma. The
      mean age was 36.6 years (33.4 in the open trauma and 41.4 in the closed). The
      left hemi-diaphragm was affected more frequently (63%) than the right (37%). The
      associated lesions were mainly of the parenchymatous abdominal organs (spleen
      43.3% and liver 49%), while in the thorax lung was involved in 20% of cases and
      heart in 3.3%. All patients underwent plastic surgical intervention of the
      diaphragm. In only one case, particularly severe, the operation consisted in
      placing a pleuric drain and death occured a few hours later. Mean mortality was
      30% (33.3% in open and 26.6% in closed traumas) and mean hospital stay was 36.2
      days. Accurate diagnosis in emergency is difficult because of the frequent
      associated lesions, typical of these patients. Despite of the optimisation of the
      rescue and the new imaging technologies, the gold standard for treatment is not
      yet reached. There is still a considerable amount of misdiagnosis, a relevant
      mean hospitalization, a high mortality and a very high morbidity. The best
      approach to thoraco-abdominal traumas is still to fear a diaphragmatic lesion up
      to contrary demonstration, in order to achieve precocious diagnosis and surgical
      treatment, to avoid complications of delayed treatment.

PMID- 15560302
TI  - [Cystic lymphangioma of the adult: our experience and review of literature].
AB  - Cystic lymphangioma is an uncommon benign pathology, usually reported in
      children, rarely in adult. Its embryopathogenesis is still controversial: it
      seems to arise from the lymphatic vessels, mainly in the cervico-cranial
      district. It is macroscopically characterised by multiple cystic non
      communicating concamerations. Definitive diagnosis used to be intraoperative and
      was usually an unexpected finding. Nowadays, with modern imaging technologies, CT
      and MRI, diagnosis can be assumed before intervention even though certain
      diagnosis can still be reached only with histological examination. Imaging
      techniques can help for a precise mapping of the lesion and definition of its
      limits with the other structures, improving therapeutic success. Various
      therapeutical options are reported in literature, but complete surgical excision
      is still considered the best approach and the most successful. The Authors report
      their experience and review the literature on cystic lymphangioma in adult.

PMID- 15560303
TI  - [Surgical treatment of varicocele in day-surgery: our experience].
AB  - Varicocele has been recognized as a treatable cause of male infertility.
      Recently, new techniques have been described for varicocele repair, including
      microsurgery, embolization and laparoscopy. The aim of this study is to evaluate
      the results of a group of patients who underwent subinguinal varicocelectomy
      using local anaesthesia in Day Surgery, after a careful ultrasonographic study to
      evaluate the degree and the quality of the reflux in the spermatic vein. The
      study shows that outpatient subinguinal varicocelectomy is a safe and reliable
      procedure. This approach is performed in local anaesthesia, has minimal morbidity
      and recurrences and, in our experience, has led an improvement in the quality of
      seminal fluid.

PMID- 15560304
TI  - [Primary adenocarcinoma of the ureter. Case report].
AB  - Primary ureteral adenocarcinoma is an infrequent histological type of urinary
      neoplasm. Many authors consider intestinal metaplasia the pivotal event of the
      pathogenetic process, whether it occurs on a pre-existing urothelial carcinoma or
      on a normal urothelium. Diagnosis is essentially based on case history and
      clinical findings (hematuria and pain) and on diagnostic imaging. Treatment is
      surgical and the ideal procedure is nephroureterectomy with excision of a bladder
      margin adjacent to the ureteral opening and ispilateral para-aortoiliac
      lymphadenectomy. A 76-year-old man with primary adenocarcinoma of the ureter case
      is reported.

PMID- 15560305
TI  - [Isolated agenesis of the gallbladder: case report].
AB  - The gallbladder agenesis is a rare congenital abnormality which is frequently
      mistaken with cholecystolithiasis, regardless of the imaging modality used. The
      diagnosis is confirmed at laparoscopic surgery with intraoperative sonography and
      intraoperative cholangiography and postoperative MRI-cholangiography.
      Intraoperative cholangiography may be risky because the absence of normal
      anatomical structures and the impossibility of pulling on the gallbladder to
      dissect the triangle of Calot represents an increased risk of iatrogenic injury
      to biliary or portal structures. Therefore postoperative MRI-cholangiography
      seems to be a more suitable approach to confirm the diagnosis.

PMID- 15560306
TI  - [Haemothorax and chylothorax: surgical approach].
AB  - Diseases causing blood accumulation in the pleural space (or haemothorax) are
      usually very demanding for diagnosis and require a multidisciplinar therapeutical
      approach in emergency. So, their treatment should always be immediate and should
      aim to restore the optimal patient's haemodynamic conditions and to find the site
      of bleeding. Chylothorax, a lymphatic effusion in the pleural space, is also a
      very important pathology, as it effects the nutritional and immunological state
      of the patient causing pleural involvement and respiratory insufficiency.
      Stabilisation of vital parameters with adequate systemic therapies (blood
      perfusions, fluids and pro-coagulation factors, TPN) preceeds surgery, which can
      be the placement of a thoracic drain or emergency thorascopy and/or thoracotomy.
      The Authors report the casistic of the latest three years for diagnosis and
      treatment of haemothorax and chylothorax stressing the advantages of a minimal
      invasive approach for evacuation and identification of the origin of bleeding and
      haemorrhage and/or lymphatic effusion control.

PMID- 15560307
TI  - [Clinical study on laparoscopic approach to cholelithiasis in the elderly].
AB  - The Authors report 66 cases of patients aged 75 years or older who underwent
      laparoscopic cholecystectomy: 28 cases presented a clinical picture of acute
      cholecystitis, 3 cases had associated common bile duct stones. A high percentage
      of patients had cardiovascular disease: 29 patients presented with cardiopaties,
      of these 9 cases had a history of myocardial infarction, 31 patients had
      artheriosclerotic hypertension, associated, in 7 patients with signs of brain
      ischemia. Five patients were suffering from Parkinson's disease, 7 were carriers
      of diabetes, 2 had liver cirrosis. Three patients were converted due to extensive
      presence of adhesions from previous surgery. Morbidity and mortality rates were
      respectively 12% and 1.5%. The Authors think that laparoscopic technique widens
      indications and reduces risks of cholecystectomy also in elderly patients.

PMID- 15560308
TI  - [Lymph node excision in differentiated thyroid carcinoma].

PMID- 15560309
TI  - [Acute pancreatitis: our experience in the light of natural history].
AB  - The Authors enumerate main steps of acute pancreatitis natural history. Then they
      discuss their last five years case-report. After having stated that clinical
      presentation depends on anatomo-pathological conditions, they consider
      aetiological causes and morphopathogenetic moments involved in the onset and
      development of this disease. They conclude stating how only proper diagnosis and
      treatment can prevent its potential evolution in multiorgan failure.

PMID- 15560310
TI  - Somatization, hysteria, or incompletely explained symptoms?

PMID- 15560311
TI  - Somatization disorder: a practical review.
AB  - OBJECTIVE: This paper reviews the present state of knowledge on the etiology,
      prevalence, diagnosis, and treatment of somatization disorder (SD). METHOD: A
      comprehensive review of the literature on SD is described under the above
      headings. RESULTS: SD is a common condition that is not well managed by many
      physicians. Patients with SD get caught between the cracks of the health care
      system, with expensive consequences. SD is a psychiatric disorder, but patients
      are reluctant to see and be treated by psychiatrists. They frequently are managed
      by nonpsychiatric physicians who have limited understanding of the condition.
      Cognitive-behavioural therapy (CBT) is the most efficacious treatment in SD,
      although antidepressants and supportive psychotherapy also have a role for some
      patients. CONCLUSIONS: A cadre of clinicians with training in the theory and
      practice of CBT for SD is required. They need to be based both in the community
      and in tertiary health care centres, where most patients with this condition are
      located.

PMID- 15560312
TI  - Explaining medically unexplained symptoms.
AB  - Patients with medically unexplained symptoms comprise from 15% to 30% of all
      primary care consultations. Physicians often assume that psychological factors
      account for these symptoms, but current theories of psychogenic causation,
      somatization, and somatic amplification cannot fully account for common
      unexplained symptoms. Psychophysiological and sociophysiological models provide
      plausible medical explanations for most common somatic symptoms. Psychological
      explanations are often not communicated effectively, do not address patient
      concerns, and may lead patients to reject treatment or referral because of
      potential stigma. Across cultures, many systems of medicine provide sociosomatic
      explanations linking problems in family and community with bodily distress. Most
      patients, therefore, have culturally based explanations available for their
      symptoms. When the bodily nature and cultural meaning of their suffering is
      validated, most patients will acknowledge that stress, social conditions, and
      emotions have an effect on their physical condition. This provides an entree to
      applying the symptom-focused strategies of behavioural medicine to address the
      psychosocial factors that contribute to chronicity and disability.

PMID- 15560313
TI  - Sexual medicine: why psychiatrists must talk to their patients about sex.
AB  - OBJECTIVE: To review the prevalence of sexual concerns and the relevance of this
      area to psychiatrists and to present evidence supporting the need for
      psychiatrists to routinely include a sex-function inquiry in the assessment of
      their patients. METHOD: A review of the recent literature was undertaken.
      CONCLUSIONS: Sex is a fundamental quality-of-life issue. Sexual problems are
      extremely prevalent among the general population and even more so among persons
      with psychiatric or medical illness. There are at least 9 reasons why all
      physicians, perhaps psychiatrists especially, should make inquiry into sexual
      behaviours and response a routine part of caring for each patient.

PMID- 15560314
TI  - The persistence of folly: critical examination of dissociative identity disorder.
      Part II. The defence and decline of multiple personality or dissociative identity
      disorder.
AB  - In this second part of our review, we continue to explore the illogical nature of
      the arguments offered to support the concept of dissociative identity disorder
      (DID). We also examine the harm done to patients by DID proponents' diagnostic
      and treatment methods. It is shown that these practices reify the alters and
      thereby iatrogenically encourage patients to behave as if they have multiple
      selves. We next examine the factors that make impossible a reliable diagnosis of
      DID--for example, the unsatisfactory, vague, and elastic definition of "alter
      personality." Because the diagnosis is unreliable, we believe that US and
      Canadian courts cannot responsibly accept testimony in favour of DID. Finally, we
      conclude with a guess about the condition's status over the next 10 years.

PMID- 15560315
TI  - Relation between prenatal maternal mood and anxiety and neonatal health.
AB  - OBJECTIVE: To examine the relation between the mood and anxiety of pregnant,
      psychiatrically treated women and neonatal health outcomes after birth. METHOD:
      We prospectively assessed 46 women treated with psychotropic medications for
      anxiety and depression during pregnancy. We compared measures of maternal mental
      health with infant outcomes, in particular, the outcomes of infants with symptoms
      of poor neonatal adaptation. RESULTS: The mothers of babies who demonstrated poor
      neonatal adaptation reported higher levels of anxiety and depression at study
      entry than did the mothers of healthy babies. This relation was not related to
      the presence or absence of treatment with clonazepam, an anxiolytic used to treat
      symptoms of anxiety. Further, increased psychiatric comorbidity in the mother was
      associated with a greater likelihood of transient symptoms in the newborn.
      CONCLUSIONS: Despite psychiatric treatment, the intensity and degree of comorbid
      symptoms appear to be related to poor transient neonatal health outcome. Our data
      suggest that, in addition to the impact of pharmacologic factors, maternal
      psychiatric status influences infant outcomes.

PMID- 15560316
TI  - Preparing psychiatry residents for the certification exam: a survey of residency
      and exam experiences.
AB  - OBJECTIVE: To determine which methods best prepare psychiatry residents for the
      certification exam, and ultimately for practice, to facilitate appropriate
      residency program curriculum changes. METHOD: We sent an anonymous survey to all
      final year (that is, PGY5) Canadian university-affiliated psychiatry residents,
      regarding frequency and diversity of observed interviews, form of feedback
      delivery, research and other training experiences, self-perception of
      preparedness and knowledge base, and management strategies for exam anxiety 6
      months before and immediately after the certification exam. RESULTS: There was a
      52% response rate. Residents from across Canada identified the following factors
      as enabling successful exam completion: regular mock orals supervised by Royal
      College examiners, clinical experience with exposure to a wide spectrum of
      pathologies, individual and group study time, and appropriate anxiety management.
      Preparation for the oral exam involving sample case vignettes with presentation
      and formulation skills training was considered to be essential but was identified
      as an area of educational and experiential weakness in some programs.
      CONCLUSIONS: To prepare psychiatry residents for successful completion of their
      certification exam, programs should incorporate regular mock orals observed by
      Royal College examiners throughout residency training (not just in PGY2 and
      PGY5). Programs should also incorporate training in case vignettes, training in
      oral exam skills, and teaching of anxiety-management strategies.

PMID- 15560317
TI  - Design and feasibility of a new cognitive-behavioural therapy course using a
      longitudinal interactive format.
AB  - OBJECTIVE: This report describes the design and feasibility of conducting a
      unique longitudinal supervision course incorporating both therapist and patient
      evaluation measures in teaching cognitive-behavioural therapy (CBT) to a group of
      mental health practitioners. METHOD: We designed a 10-session longitudinal
      supervision course to teach CBT by applying key continuing medical education
      (CME) principles. Each session consisted of 30 minutes of didactics and
      demonstrations followed by 90 minutes of group case supervision. Course
      participants were mental health practitioners who treated patients from their own
      practice; most of the patients suffered from a depressive and (or) anxiety
      disorder. We assessed therapists for CBT skill acquisition at the beginning and
      at the end of the course, using the Cognitive Therapy Scale (CTS). We assessed
      patients' symptoms weekly, using the Beck Depression Inventory, the Beck Anxiety
      Inventory, and the Clinical Global Impression scale. RESULTS: A total of 34
      participants enrolled in three 10-session courses. Most participants submitted
      audiotapes for rating at the beginning and end of the course, and most submitted
      patient symptom information. CONCLUSIONS: This course shows promise as an
      effective way to teach complex skills in CBT to mental health providers. In
      limited samples, the course showed clear improvement in therapist adherence to
      CBT and in patients' clinical outcomes. Future research is required to validate
      the potential benefit of this CME intervention for mental health practitioners
      treating patients with mood and anxiety disorders.

PMID- 15560318
TI  - Acceptability and disintegration rates of orally disintegrating risperidone
      tablets in patients with schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: To investigate the disintegration profile, acceptability, and
      tolerability of orally disintegrating risperidone tablets in patients with
      schizophrenia or schizoaffective disorder. METHOD: Ten patients stable for at
      least 10 days on monotherapy with oral risperidone 2 mg to 4 mg taken once daily
      were switched for 7 days to an equivalent dosage of orally disintegrating
      risperidone. Visual assessments for time to initial and complete disintegration
      were collected at each visit. Clinical Global Impression of Severity scores were
      collected at baseline and at the last visit. Patient acceptance of the new
      formulation, rated according to a visual analog scale, was obtained at the last
      visit. RESULTS: All patients maintained stable clinical status. Mean time to
      initial disintegration was 5.1 seconds, SD 0.8, and mean time to complete
      disintegration was 29.4 seconds, SD 18.4. The formulation was rated as very
      acceptable. Adverse events were reported by 5 patients; all were mild.
      CONCLUSION: The orally disintegrating risperidone tablets were well tolerated and
      rated as very acceptable by all patients.

PMID- 15560319
TI  - Mirtazapine for treatment of nausea induced by selective serotonin reuptake
      inhibitors.

PMID- 15560320
TI  - Effects of propofol on electroconvulsive therapy seizure duration.

PMID- 15560321
TI  - Deliberate ingestion of peanut as a suicide attempt.

PMID- 15560322
TI  - Postoperative manic outburst: a case report.

PMID- 15560323
TI  - Road rage: old wine in a new bottle.

PMID- 15560324
TI  - The effect of quetiapine on cannabis use in 8 psychosis patients with drug
      dependency.

PMID- 15560325
TI  - Sex-related developmental differences in the lateralized activation of the
      prefrontal cortex and amygdala during perception of facial affect.
AB  - The lateralization of cognitive abilities is influenced by a number of factors,
      including handedness, sex, and developmental maturation. To date, a small number
      of studies have examined sex differences in the lateralization of cognitive and
      affective functions, and in only few of these have the developmental trajectories
      of these lateralized differences been mapped from childhood through early
      adulthood. In the present study, a cross-sectional design was used with healthy
      children (n=7), adolescents (n= 12), and adults (n= 10) who underwent functional
      magnetic resonance imaging (fMRI) during a task that required perceiving fearful
      faces. Males and females differed in the asymmetry of activation of the amygdala
      and prefrontal cortex across the three age groups. For males, activation within
      the dorsolateral prefrontal cortex was bilateral in children, right lateralized
      in adolescents, and bilateral in adults, whereas females showed a monotonic
      relationship with age, with older females showing more bilateral activation than
      younger ones. In contrast, amygdala activation was similar for both sexes, with
      bilateral activation in children, right-lateralized activation in adolescents,
      and bilateral activation in adults. These results suggest that males and females
      show different patterns of lateralized cortical and subcortical brain activation
      across the period of development from childhood through early adulthood.

PMID- 15560326
TI  - Does augmented feedback from pedometers increase adults' walking behavior?
AB  - This study investigated whether feedback from pedometers motivated adults to
      increase their walking behavior. Participants (n =26) were enrolled in one of two
      8-wk. "Walking for Fitness" classes. The study used a crossover design, such that
      Group 1 wore pedometers for the first 3 weeks (Feedback Condition) and sealed
      "disguised" pedometers for the last 3 weeks (No-feedback Condition). The order of
      feedback was reversed for Group 2. Analysis indicated that (a) neither group
      increased their walking behavior significantly over time and, (b) interactions
      between groups were not significant at Week 3 or 6, indicating that groups did
      not respond differently to feedback from the pedometers. If a motivational effect
      from pedometers exists, it may be small, dissipate before 3 wk., only work in
      combination with goal setting, or only motivate certain types of individuals.

PMID- 15560327
TI  - Expertise in cognitive psychology: testing the hypothesis of long-term working
      memory in a study of soccer players.
AB  - This experiment compared several theories of expertise and exceptional
      performances in cognitive psychology. One current conception assumes that experts
      in a specific domain have developed a long-term working memory, which accounts
      for the difference in memory performance between experts and novices. The
      principal characteristics of this memory are the speed with which processes of
      storage and retrieval function and the existence of retrieval structures that
      allow a temporary activation of the knowledge store in long-term memory. Other
      authors such as Vicente and Wang argue this notion does not account for memory
      performance that is not intrinsic to the domain of expertise. We attempt to
      clarify the two viewpoints and to focus on this debate by testing the hypothesis
      of long-term working memory using soccer as the domain of expertise and by
      comparing the cognitive performance of participants who have different expertise
      (novices, supporters, players, and coaches). 35 male participants were
      administered a new version of the Reading Span test to assess their long-term
      working memory according to two conditions. In the first condition (structured
      condition), the last word of each sentence was related to the soccer domain, and
      these words were related to each other in such a manner that they represented a
      part of the game. In the second condition (unstructured condition), the last word
      of each sentence was related to soccer but these words did not represent part of
      the game. Analysis showed that the sentence span increased as a function of
      expertise for the structured condition but not for the unstructured condition.
      The results were interpreted in the framework of the constraint attunement
      hypothesis proposed by Vicente in 1992 and the long-term working memory
      hypothesis proposed by Ericsson and Kintsch in 1995.

PMID- 15560328
TI  - Possible influence of linguistic musical background on perceptual pitch-matching
      tasks: a pilot study.
AB  - Linguistic background has been identified as important in the perception of
      pitch, particularly between tonal versus nontonal languages. In addition, a link
      between native language and the perception of musical pitch has also been
      established. This pilot study examined the perception of pitch between listeners
      from tonal and nontonal linguistic cultures where two different styles of music
      originate. Listeners were 10 individuals born in China who ranged in age from 25
      to 37 years and had spent on the average 30 mo. in the USA and 10 individuals,
      born on the Indian subcontinent, who ranged in age from 22 to 31 years, and had
      spent an average of 13 mo. in the USA. Listeners from both groups participated in
      two conditions. One condition involved listening to a selection of music
      characteristic of the individual's culture (China, pentatonic scale; Indian
      subcontinent, microtones), and one condition involved no music. All listeners
      within each condition participated in two voice pitch-matching tasks. One task
      involved matching the lowest and highest pitch of tape-recorded voices to a note
      on an electronic keyboard. Another task involved matching the voice pitch of tape
      recorded orally read words to a note on the keyboard. There were no differences
      between the two linguistic groups. Methodological limitations preclude
      generalization but provide the basis for further research.

PMID- 15560329
TI  - Relation between polysomnographic measures during nocturnal sleep and a quotient
      of behavioral development in infants with developmental disabilities.
AB  - Polysomnographic features during nocturnal sleep were investigated in 27 infants
      with developmental disabilities. With the use of a multiple regression analysis,
      78% of the variance of a Development Quotient (DQ) measured by a questionnaire on
      behavioral development for infants was explained by sleep measures. Of 14 sleep
      measures employed in the study, (1) cumulative awakening time during a nocturnal
      sleep time, (2) duration of REM stage, and (3) percentage of REM to total sleep
      time were important in association with the DQ. The findings are consistent with
      the sleep-cognition hypothesis proposed by Espie, et al.

PMID- 15560330
TI  - Singaporean education students' perceptions of knowledge and skills as important
      for teachers.
AB  - This paper examined perceptions of knowledge and skills important for teachers of
      353 Singaporean undergraduate students. They rated higher teaching and nurturing
      skills and gave moderate ratings to theoretical knowledge and research skills.
      There is a need to raise teachers' awareness of educational research and
      theoretical innovation for classroom practice.

PMID- 15560331
TI  - Body-esteem in Swedish 10-year-old children.
AB  - This study examined body-esteem in 10-yr.-old children. The study group comprised
      960 schoolchildren, 515 girls and 445 boys (M age= 10.4, SD=0.5). Analysis showed
      that girls who were overweight had more negative body-esteem on all dimensions
      (weight, appearance, and attribution). The overweight boys had more negative
      perceptions on only two dimensions (weight and appearance). Twice as many girls
      perceived themselves as too fat (20%) as too skinny (10%). Of the girls who
      perceived themselves as fat, only 31% were overweight; similarly only 33% of the
      boys who perceived themselves as fat were overweight. The children's perception
      of their weight seemed as important as their actual weight and was associated
      with their body-esteem in the same way. Although few children had dieted (7% of
      the girls and 5% of the boys), the ones who had dieted had more negative body
      esteem than children who had not dieted.

PMID- 15560332
TI  - Discrimination and production of English vowels by bilingual speakers of Spanish
      and English.
AB  - The goal of this study was to examine whether listeners bilingual in Spanish and
      English would have difficulty in the discrimination of English vowel contrasts.
      An additional goal was to estimate the correlation between their discrimination
      and production of these vowels. Participants (40 bilingual Spanish- and English
      speaking and 40 native monolingual English-speaking college students, 23-36 years
      of age) participated (M age = 25.3 yr., Mdn = 25.0). The discrimination and
      production of English vowels in real and novel words by adult participants
      bilingual in Spanish and English were examined and their discrimination was
      compared with that of 40 native monolingual English-speaking participants.
      Stimuli were presented within triads in an ABX paradigm. Novel words were chosen
      to represent new words when learning a new language and to provide a more valid
      test of discrimination. Bilingual participants' productions of vowels were judged
      by two independent listeners to estimate the correlation between discrimination
      and production. Discrimination accuracy was significantly greater for native
      English-speaking participants than for bilingual participants for vowel contrasts
      and novel words. Significant errors also appeared in the bilingual participants'
      productions of certain vowels. Earlier age of acquisition, absence of
      communication problems, and greater percentage of time devoted to communication
      contributed to greater accuracy in discrimination and production.

PMID- 15560333
TI  - Perceived psychological stress among high school basketball officials.
AB  - The purpose of this study was to survey certified high school basketball
      officials during midseason to assess whether the sources and magnitude of
      perceived psychological stress would be consistent with previous studies of
      officials in other sports. The sources and magnitude of perceived psychological
      stress were measured among 324 high school basketball officials (N=324; 312 men,
      12 women) using a revised version of the Ontario Soccer Officials Survey. The
      mean age was 37.6 yr. (SD= 9.4), and the mean years of basketball refereeing
      experience was 11.7 yr. (SD=8.3). A random sample (N=498) of all basketball
      officials in a midwestern state (N=1,011) was used, and 324 of the surveys were
      returned (65%). The overall variance accounted for with the four factors was
      84.7%. The magnitude of stress for these factors ranged from below mild to
      moderate.

PMID- 15560334
TI  - Generalization of achievement orientations for experiences of success and failure
      in youth sport.
AB  - Studies of achievement orientations in sport have focused on subjective success.
      This study explored the extent to which these orientations generalize to
      subjective failure. 796 youth sport participants ages 9 to 16 years (338 boys,
      458 girls) recalled personal experiences of success and failure. These were then
      categorized as mastery, comparison or social recognition orientations. In 60% of
      cases, participants used the same orientation to interpret success and failure.
      In the middle and oldest groups, such generalization was most frequent for
      mastery orientations in girls but for comparative orientations in boys. In the
      youngest groups, mastery orientations generalized most frequently for each sex.
      Hence achievement orientations generalized across type of experience, but with
      differences by age and sex.

PMID- 15560335
TI  - Body image, figure rating, and body mass index of girls enrolled in health,
      physical education, or athletics classes.
AB  - The aim was to examine associations among body-image, figure rating, and Body
      Mass Index of seventh grade girls who chose health, physical education, or
      athletics classes. Measurements were taken prior to and following the course.
      Class choice was significantly related to body-image satisfaction but not to
      figure rating or Body Mass Index. Research is needed to examine inaccurate self
      perception of fatness in underweight girls, whether there is a higher risk for
      eating disorders for students in athletics and physical education classes,
      whether the curriculum is effective with students in physical education and
      athletics, and why girls who chose the health class began with higher body-image
      satisfaction than those in physical education or athletics, even though their
      Body Mass Index and figure-rating size did not differ.

PMID- 15560336
TI  - Relationships between physical activity and motor skills in middle school
      children.
AB  - The purpose of this study was to examine the relationships between physical
      activity measured as pedometer steps and performance on three motor skill tests.
      A secondary purpose was to determine if middle school children are meeting the
      recommendation for the number of daily steps. A sample (n =217) of 6th, 7th and
      8th grade students participated. Each subject wore a Digi-Walker pedometer for
      three consecutive days. Subjects additionally recorded their pedometer steps in
      two 45 min.-physical education classes. There were strong significant
      correlations between daily steps taken by boys and girls, pedometer steps during
      physical education class and the AAHPERD Passing Test and the Bass Stick Balance.
      Similar correlations were weaker for the Side-Step Agility Test. Multivariate
      analysis of variance was utilized to examine variability of the three skills test
      by sex and year in school. Differences between students in Grades 7 and 8 on the
      AAHPERD Passing Test were significant. In addition, significant differences
      between daily pedometer steps and steps during physical education between Grades
      6 and 7 were observed. Boys and girls had similar means on the AAHPERD Passing
      Test and Bass Stick Balance Test, but not on the Side-Step Agility Test. Scores
      on the three movement skills tested in this study were not strongly related to
      physical activity of the entire sample. Steps taken by middle school children
      appear not to be related to these measures of motor skills.

PMID- 15560337
TI  - Effects of illusory stripes on the Helmholtz illusion.
AB  - This study examined the Helmholtz illusion by using "illusory stripes." A square
      patch is perceived as wider when vertical lines are drawn on it and is perceived
      as taller when horizontal lines are drawn on it, i.e., Helmholtz illusion. With
      vertical lines curved sinusoidally, horizontal "illusory stripes" are perceived;
      and with horizontal lines curved sinusoidally, vertical "illusory stripes" are
      perceived. The purpose of the present study was to test whether the "illusory
      stripes" produce the Helmholtz illusion. We measured the apparent size of a
      square patch filled with sinusoidal lines. Our subjects (N=27) judged the patch
      with horizontal "illusory stripes" taller than the square patch filled with
      vertical straight lines. The subjects also judged the square patch with vertical
      "illusory stripes" wider than the square patch filled with horizontal straight
      lines. These results demonstrate that "illusory stripes" can produce the
      Helmholtz illusion.

PMID- 15560338
TI  - Depth perception of elementary school students with qualitatively evidenced
      locomotor impairments.
AB  - The purpose of the study was to examine differences in depth perception of
      students classified according to their gross locomotor skills. The seven
      qualitative gross locomotor tasks of Ulrich's Test of Gross and Motor Development
      were used to classify 162 students as either motor impaired (n1 =27) or
      nonimpaired (n2= 135). The Howard Dollman Apparatus was used to measure depth
      perception. Analysis showed that the motor-impaired group scored significantly
      lower than the nonimpaired group on depth perception. Discriminant function
      analysis indicated that only the running task separated the students by depth
      perception scores. Subsequent multiple regression analysis confirmed that the
      running task, along with sliding and galloping, were significant predictors of
      the students' perception of the third dimension. Physical educators working with
      students with gross locomotor impairments or low perception of the third
      dimension need to adjust their teaching and offer opportunities for successful
      involvement in physical education classes and sports.

PMID- 15560339
TI  - Correlations among handedness, eyedness, monocular shifts from binocular focal
      point, and nonverbal intelligence in university mathematics students.
AB  - Relationships among hand preference, nonverbal intelligence, and the monocular
      shifts of binocular focal point were studied in 33 men and 12 women university
      mathematics students. Ocular dominance was assessed with the Miles test. The
      monocular shift of binocular focal point for each eye was assessed with a
      modified Miles test. Hand preference was assessed on the Edinburg Handedness
      Inventory. Nonverbal intelligence was assessed with Cattell's Culture Fair
      Intelligence Test. In a prior study, the percentage of left-eye preference had
      been reported to be greater for mathematics students than for nonmathematics
      students. In the present study there were positive correlations between hand
      preference and the sum of the monocular shifts of two eyes. In addition, there
      was a negative correlation between nonverbal intelligence and the sum of the
      monocular shifts of two eyes. As these resultssuggest that the sum of the
      monocular shifts of two eyes may be related to mathematical ability and nonverbal
      intelligence, further research with a larger sample including non-mathematics
      students is needed.

PMID- 15560340
TI  - Sleep quality, sleep propensity and academic performance.
AB  - We examined associations between measures of sleep propensity on the Epworth
      Sleepiness Scale, sleep quality on the Pittsburgh Sleep Quality Index and
      academic performance by GPA and grades in introductory psychology for 414
      students. In the total sample, neither sleep propensity nor sleep quality
      correlated with GPA or introductory psychology grades. However, among students
      carrying a full course load, those reporting poor sleep quality performed less
      well on academic measures than those reporting a better quality of sleep. Further
      research is needed to assess the moderating influence of overall demands of
      daytime functioning on the association between sleep quality and academic
      performance.

PMID- 15560341
TI  - Self-corrected elaboration effects on incidental memory.
AB  - Subjects performed an orienting task involving 3 conditions followed by an
      unexpected free recall test. The conditions were designed to force 3 types of
      corrected elaborations: Generated Correction, Chosen Correction, and No
      Correction. In the Generated Correction condition the subjects were presented
      with a target word (e.g., Baby) and a bizarre sentence frame (e.g., "____drinks
      beer.") and asked to correct the target to a congruous word (e.g., Uncle) to make
      a common sentence. In the Chosen Correction condition, the subjects were
      presented with a target and its bizarre sentence frame and asked to choose one of
      the alternative congruous words (e.g., Uncle, Aunt) to make a common sentence. In
      the No Correction condition, the subjects were presented with a target and its
      bizarre sentence frame and asked to rate the congruity of each target to its
      sentence frame. Generated Correction led to a better performance than Chosen
      Correction and No Correction, but a difference between the last two correction
      types was not found. These results were interpreted as showing that, by
      generating correct information, self-corrected elaboration led to facilitation of
      incidental memory.

PMID- 15560342
TI  - Comparison of the RT3 Research Tracker and Tritrac R3D accelerometers during a
      backpacking expedition by a single subject.
AB  - This study compared the RT3 Research Tracker accelerometer and the Tritrac R3D
      accelerometer in a field setting. A six-day backpacking expedition (122.4 km in
      length) was completed by a single subject in the Grand Canyon National Park,
      Arizona. The overall correlation between the counts of vector magnitude activity
      for the RT3 and R3D was moderate (r =.75, p<.001), with the overall calculated
      bias [mean difference (RT3 minus R3D) and standard deviation of the differences]
      across all six days estimated at 235+/-436 vector magnitude activity counts.
      However, agreement between the instruments is problematic; the RT3 might be 201
      activity counts below or 671 activity counts above the R3D in assessing physical
      activity during backpacking.

PMID- 15560343
TI  - Effect of an interference task on a ball-hitting skill by 6- to 10-yr-old
      children.
AB  - We explored the functionality of interference on a forehand tennis shot among 145
      6- to 10-yr.-old children using the retroactive interference procedure. First,
      the children were asked to execute 10 forehand drives with a small tennis racquet
      (prime test). They were then asked to execute 10 frontal returns (interference
      test). The final probe test was similar to the first test, but children executed
      only 3 forehand drives. Children were assessed using a developmental category for
      the forehand drive skill. Each developmental step reflected a common sequence of
      body configurations exhibited by all individuals and was evaluated point-by
      point. Multivariate analysis showed that boys had higher ratings of developmental
      steps of coordination than girls and that the rated developmental step initially
      increased with age before stabilizing. The developmental steps of coordination
      decreased after the interference task. We also showed that interference
      mechanisms are operative for this gross motor skill in childhood, but no
      interaction was found with age and sex. Post hoc analysis showed that
      developmental steps were not significantly different after the interference task
      for the oldest children, suggesting the onset of the inhibitory process.

PMID- 15560344
TI  - Visual attention in young adulthood after cardiopulmonary resuscitation at birth
      or being born small for gestational age.
AB  - The Posner cue-target paradigm for the study of shifts in visual attention was
      used to assess focused attention and shifts in attention in 43 young adults, 19
      to 28 years of age, who had been in need of cardiopulmonary resuscitation at
      birth because of perinatal asphyxia (n=31) or who were born small for gestational
      age (n= 12). Their performances were compared to that of 18 control subjects. The
      subjects resuscitated at birth were divided into two groups, mild and moderate,
      according to neurological symptoms during the neonatal course. An expected
      significant main effect by block of trials and conditions was found, with general
      decrease in reaction times from Blocks 1 to 5 and with slowest reaction times to
      an invalid cue and fastest to a valid one. No group differences were
      statistically significant, but the moderate asphyxia and the groups small for
      gestational age had longer average reaction times on all test conditions than
      control subjects, implying that those who showed the most severe pre- or neonatal
      complications also were most affected in attentional functions.

PMID- 15560345
TI  - Validity of test score interpretations for three self-concept measures based on
      differing theoretical models.
AB  - Three theoretical models have been proposed to represent self-concept: (a)
      unidimensional; (b) multidimensional; (c) multidimensional hierarchical.
      Inventories have been developed under each of the three competing theoretical
      models; which model best represents self-concept is unclear. Typically, self
      concept construct validation has utilized various approaches including
      correlational, multitrait-multimethod, and factor analytic methods. Another
      method, however, for assessing validity would be to determine the consequences of
      score interpretations using different measures specific to each of the
      theoretical models. This paper examined Messick's notion (1989) of the validity
      of test-score interpretations as applied to three of the most widely used
      measures derived under each of the three different theoretical models of self
      concept. Results suggest that overall multidimensional measures are more
      consistent in classifying individual's self-concept than unidimensional measures.

PMID- 15560346
TI  - Identification with sports teams by fans of women's sports.
AB  - Previous studies on why sports fans identify with a particular team have focused
      on fans of men's sports teams. This study examined why fans favor a particular
      women's sports team. Based on survey responses from 273 self-identified fans of
      women's sports, athletes are most frequently cited as the reason for choosing a
      favorite women's sports team.

PMID- 15560347
TI  - Stress symptoms one year after 9/11/01: a follow-up.
AB  - This study investigated whether stress symptoms related to attention deficit
      previously found for a sample (n= 149) of Chicago-area college students 1 to 5
      weeks after the September 11th attacks were present in a comparable sample (n =
      129) 12 to 14 months later. As hypothesized, the later participants had a
      significantly lower mean score on the scale, Attention Deficit of the Smith
      Stress Symptoms Inventory, than a different group of participants tested
      immediately after the attacks. Mean Attention Deficit scores for groups after one
      year and immediately before September 11th (n=320) did not differ statistically.
      Findings are consistent with the interpretation that elevations in scores on
      Attention Deficit immediately after September 11th were indeed associated with
      the catastrophic attacks and not artifacts of time of examination. Consistent
      with previous research with this inventory, disaster-related traumatic stress
      scores are lower over time, although here no control group was included.

PMID- 15560348
TI  - Factors associated with helplessness among Japanese collegiate swimmers.
AB  - In this study the factors that lead to learned helplessness among Japanese
      collegiate swimmers were examined. Participants were 135 men and 72 women
      swimmers (ages 18 to 22 years). A Sports Attributional Style Scale measuring
      helplessness in performance and daily life was administered, and the participants
      were divided into two groups: those scoring high and low. Analysis indicated that
      (1) there was no significant correlation between helplessness scores and
      performance. (2) The group scoring high on learned helplessness reported a strong
      tendency towards helplessness not only in competitive life but also in daily
      life, which implied the generalization of helplessness. (3) The tendency to
      helplessness in performance was more closely related to the attributional style
      of positive events than negative events. In conclusion, some factors involved in
      helplessness among athletes can be explained by the theory of learned
      helplessness; however, some characteristics of athletes may be better described
      by attributional style in positive events.

PMID- 15560349
TI  - Relative contributions of perceived mattering to parents and friends in
      predicting adolescents' psychological well-being.
AB  - Perceived mattering is the psychological tendency to perceive the self as
      significant to specific other people. The central goal of this study was to
      examine whether adolescents' perceived mattering across social spheres (parents
      and friends) is addtive or compensatory in predicting adolescents' psychological
      well-being. Tests of the relative importance of adolescents' perceived mattering
      to parents and friends for psychological well-being were conducted using data
      from two convenience samples. Study 1 participants were, on the average, 17.5 yr.
      old and living in rural northwestern United States (N=128, 50% male, n=64; 50%
      female, n=64). Study 2 participants, on the average, were 16.9 yr. old, from a
      suburban western Canadian region (N=532, 51.4% male, n=273; 48.6% female, n=259).
      Hierarchical regression analysed with indicators of self-concept and behavioral
      misconduct as dependent variables used perceived mattering to parents and
      perceived mattering to friends and the interaction between these two variables as
      independent variables. Perceived mattering in both social spheres seemed the
      optimal condition for adolescents. Perceived mattering to friends "added" to
      perceived mattering to parents in explaining variance in assessments of
      psychological well-being in both studies.

PMID- 15560350
TI  - Teaching speech sounds to young children using randomly ordered, variably complex
      task sequences.
AB  - Three children, ages 4:8 to 5:11, were taught a speech sound using a randomly
      ordered variably complex task sequence (concurrent treatment), in which practice
      occurred in randomized easy-to-hard tasks. In an AB research design replicated
      across participants, the children quickly advanced to 60% accurate productions of
      the target speech sound and displayed generalization to untaught tasks.

PMID- 15560351
TI  - Relationships between physiological and psychological stress and salivary
      immunoglobulin A among young female gymnasts.
AB  - We investigated whether psychological and physical stress induced by training or
      competition influence the secretory immune system among 12 highly trained young
      female gymnasts. Salivary levels of secretory IgA and cortisol responses to
      gymnastic training session or competition were assessed a total of 10 times,
      immediately before and after two training sessions which had different
      intensities and just before and after a major competition. These parameters were
      also measured on two non-training days. The Brunel Mood Scale was also used to
      assess the gymnasts's overall mood on each test day. IgA:Protein ratio was
      calculated. Significant decreases in this ratio were found after each exercise
      session, related to the physiological and psychological stress induced by
      exercise. Over the 5-mo. training period the presession IgA:Protein ratios were
      unchanged. Gymnasts registered any episodes of upper respiratory tract infection.
      Bouts of exercise induce transitory effects on the immune system in relation to
      the workload and the stress induced by the exercise without any relation to
      increased susceptibility to illness in children.

PMID- 15560352
TI  - Relationships between mood state, time estimation, and selected movement speed.
AB  - We investigated whether different aspects of mood state influence sense of time
      estimation and movement speed. Mood states were measured on the Multiple Mood
      Scale for 142 female undergraduate students, who were then asked to estimate the
      interval of time elapsed between the words "start" and "stop" spoken by a tester.
      Next, the same subjects were told to draw circles inside 1-cm squares printed on
      an A4 size sheet of paper in succession at their freely elected comfortable
      speed. Scores on Concentration (r=-.22, p<.01) and Being Startled (r=-.26, p<.01)
      each correlated significantly and negatively with time estimation, while scores
      on Boredom (r =.17, p <.05) had a significant positive correlation with movement
      speed. These results suggest that different aspects of mood state have some
      association with time estimation and selected movement speed. Values account for
      small common variance.

PMID- 15560353
TI  - Reliability and validity of scores on the Slosson Visual Perceptual Skill
      Screener.
AB  - Psychometric characteristics of the Slosson Visual Perceptual Skill Screener were
      studied using three independent samples of 595 boys and 578 girls ages 5 to 10
      years. Adequate characteristics for item selection were indicated by item
      difficulty (Mdn=.49) and item discrimination (Mdn=.59). Interitem consistency of
      .93 (n1 = 1,045) was recorded for the total scale, while 30-day test-retest
      reliability was .80 (n2=55). Convergent validity was estimated using the Bender
      Visual-Motor Gestalt test (Koppitz developmental scoring system; r = .43, n3=47),
      the Developmental Test of Visuo-motor Integration, Visual Perception subtest (r
      =.62, n3 =73), and the Test of Visual Perceptual Skills-Revised-Nonmotor Total
      Score (r = .63, n2 =59).

PMID- 15560354
TI  - Temporal stability of the sleep disturbance ascribed to worry scale.
AB  - This study examined the test-retest reliability of the Sleep Disturbance Ascribed
      to Worry Scale. College students (N= 116) completed the scale twice over a 1-mo.
      interval. The test-retest correlation was .83, indicating satisfactory temporal
      stability.

PMID- 15560355
TI  - High school, college, and professional school faculty members' perceptions of
      students who are current smokers, former smokers, and nonsmokers.
AB  - A questionnaire rating the descriptions of a hypothetical student smoker, a
      former smoker, and a nonsmoker, as well as personal smoking habits, was
      administered to 35 high school, 34 college, and 24 professional school faculty
      members. Respondents rated smokers more negatively than nonsmokers or former
      smokers. Paired-sample t tests indicated that smokers were rated as less
      intelligent, independent, conscientious, and ambitious and as having poorer
      judgment and being more hostile than the nonsmoking student. In addition, paired
      sample t tests identified only one significant difference out of seven between
      the ratings of the former smoker and the nonsmoker; the former smoker was rated
      less artistically creative than one who had never smoked. High school teachers'
      ratings of students who smoked relative to nonsmokers were more negative than
      those of college and professional school faculty, suggesting that high school
      student smokers might be especially socially penalized for their decision to
      smoke.

PMID- 15560356
TI  - Moral development and form of participation, type of sport, and sport experience.
AB  - The present study investigated aspects of moral development in sport, according
      to the form of participation, type of sport, and sport experience. 510
      participants, 14 to 49 years of age (M=24.9, SD=8.3) who came from organized
      competitive sports included athletes (n=327), referees (n=138), and coaches
      (n=45) in football (n = 161), handball (n = 198), and basketball (n = 150). Years
      of sport experience ranged from 1 to 6, 7 to 14, and 15 to 30 years of
      participation in sports. The Defining Issues Test was given; analysis showed no
      significant differences in development of moral reasoning among participants
      across different types of sports, forms of participation, and years of experience
      in sport.

PMID- 15560357
TI  - Statistical analysis for finger tapping with a periodic external stimulus.
AB  - In this paper we outline an experiment in which seven subjects attempted to tap
      in synchrony with a pacing stimulus with the interstimulus interval that varied
      in a cycle (T,T+dT,T, T-dT) repeating every fourth interval, where T represents
      an unexpected step change of an interstimulus interval. Conditions included three
      levels of T= (400, 500, and 600 msec.) with four levels of dT= 1, 3, 5, and 7% of
      T). The statistical analysis indicated that small changes in T lead to rapid
      matching of the interresponse intervals to the new interstimulus intervals even
      when the variation in the input is not apparent to subjects.

PMID- 15560358
TI  - Recognition accuracy and reaction time of vocal expressions of emotion by African
      American and Euro-American college women.
AB  - This study examined the relationship of racial group membership and vocal
      expressions of emotion. Recognition accuracy and reaction time were examined
      using the Diagnostic Assessment of Nonverbal Accuracy 2 Receptive Paralanguage
      subtests with 18 young Euro-American and African-American women. Participants
      listened to Euro-American children and adults speaking a neutral sentence, and
      identified the emotion as happy, sad, angry, or fearful. Analysis identified a
      significant effect for race on reaction time. Euro-American participants had
      faster mean RT than the African-American women for the recognition of vocal
      expression of emotion portrayed by Euro-Americans. However, no significant
      differences were found in mean accurate identification between the two groups.
      The finding of a significant difference in recognition RT but not in accuracy
      between the stimuli spoken by an adult and a child was unexpected. Both racial
      groups had faster mean RT in response to vocal expression of emotion by children.

PMID- 15560359
TI  - Perceptions of causes of performance-related injuries by music health experts and
      injured violinists.
AB  - Skilled violin and viola players, all of whom had a current performance-related
      musculoskeletal injury, were asked to report their perceptions of contributing
      risk factors, consistent with a participatory ergonomics approach. The 26
      players, age 18 to 60 years, had been playing for a minimum of 10 years and
      averaged three hours of practice per day. In addition, 7 music health experts,
      all with more than 10 years of clinical experience in treating musicians, were
      asked to report on the risk factors for musicians' performance-related injuries.
      A high correlation between the perceptions of these two groups was found, with
      the same top five factors in terms of severity indicated by both groups. Factors
      rated as high risk were primarily intrinsic and related to the manner in which
      respondents practiced, to playing posture, and to flaws in skill technique.

PMID- 15560360
TI  - Endogenous opioids, blood pressure, and diffuse noxious inhibitory controls: a
      preliminary study.
AB  - A 2003 study suggested that there are age differences in diffuse noxious
      inhibitory controls (DNIC), a form of endogenous pain inhibition. The present
      report describes a followup study employing a pharmacological blockade of
      endogenous opioids, i.e., using naloxone, in a small subset (n=6) of healthy
      young volunteers to characterize the opioid-dependence of DNIC, as well as DNIC's
      association with cardiovascular reactivity. Findings suggested that, while opioid
      blockade enhanced cardiovascular reactivity to cold pain, DNIC was not affected
      by administering naloxone. Interestingly, greater cardiovascular responses to
      noxious cold were associated with enhanced DNIC in this small sample. This
      relationship, which did not appear opioid-dependent, supports previous models
      integrating cardiovascular activity with the functioning of pain-modulatory
      systems.

PMID- 15560361
TI  - Using RPE to regulate exercise intensity during a 20-week training program for
      postmenopausal women: a pilot study.
AB  - Feelings of effort sense quantified via the Borg Rating of Perceived Exertion
      (RPE) scale have been validated for regulating exercise intensity. Most studies
      validating RPE for exercise prescription have used young, male subjects and only
      a few exercise sessions. As part of a larger study we examined the accuracy of
      RPE for regulating exercise intensity in a group of postmenopausal women. Six
      women (70.0+/-7.1 yr.) were given a maximal graded exercise test. Target RPEs
      equivalent to 40%, 50% and 60% VO2 max were developed from this test using
      standard techniques. These RPEs were used to regulate intensity during a 20-wk.
      training program. During the initial 5 wk. of training target intensity was
      increased from 40% to 60% VO2 max and exercise duration from 15 to 30 min.
      Accuracy of exercise intensity regulation was determined by comparing the heart
      rate during exercise to a target heart rate equivalent to the desired %VO2 max.
      At Week 2 of training (target 40% VO2 max) the mean intensity produced did not
      differ from target. During Weeks 4 (target 50% VO2 max), 6 and 10 of training
      (target 60% VO2 max) the mean exercise intensity was below target. At Week 20 the
      mean intensity produced was not different from target. This suggests that elderly
      women can accurately use RPE to regulate exercise intensity, but at intensities
      above 40% VO2 max an acclimation period is needed.

PMID- 15560362
TI  - Human figure drawing size and body image in preschool children from a self
      physique perspective.
AB  - To learn about the relationship between size of human figure drawings and the
      physiques of children, we investigated body image characteristics in childhood by
      using the Human Figure Drawing test. Height, weight, Kaup Index (a body mass
      index for children) and Human Figure Drawing traits (vertical height, horizontal
      width, waist size, surface area of head, surface area of the self-drawing) were
      measured for drawings of 122 4- to 6-yr.-old children (62 boys, 60 girls).
      Analysis showed that boys, who are physically larger than girls, produced self
      drawings with somewhat larger surface areas. For vertical height of self-drawings
      of boys, 4-yr.-olds characteristically made taller self-drawings than 5-yr.-olds.
      While we hypothesized that taller children would make vertically taller self
      drawings, we observed a negative relationship between children's physical height
      and the vertical height of the self-drawings. 4-yr.-old boys showed the most
      interest in their own physical height, making taller drawings and in doing so
      gave a clue to an early childhood feature of body image.

PMID- 15560363
TI  - Strength training effects on physical conditioning and instep kick kinematics in
      young amateur soccer players during preseason.
AB  - The purpose of this study was to examine effects of lower limb strength training
      on physical conditioning and kinematic characteristics of instep kicking in 16
      young amateur soccer players who participated in initial and final laboratory
      tests. In addition to their standard preseason soccer program, 8 players
      comprised the experimental group, who performed an 8-wk. strength-training
      program. Maximal and relative isometric force of the lower limbs were
      significantly improved. Moreover, toe and ankle linear velocity during ball
      contact, ball velocity, as well as ankle, knee and hip angular velocities of the
      kicking leg were significantly increased. It is concluded that conditioning and
      kinematic indices of the kicking performance could be improved after strength
      training of the lower limbs.

PMID- 15560364
TI  - Premotor and motor reaction time of educable mentally retarded youths in a
      Taekwondo program.
AB  - This study investigated the educational effect of a Taekwondo program on premotor
      and motor reaction time in high school students who were mentally retarded but
      educable. Subjects were voluntarily recruited from the Special High School for
      the Mentally Retarded in Busan, South Korea. Subjects were divided into a trained
      group (n = 10) and a control group (n = 10) with balanced ages, physical
      conditions, and IQ. Subjects took part in pretests after practicing a Taekwondo
      motion 10 times with a signal presented randomly between 2 and 8 sec. after
      "Ready!" The motion was raising the right knee powerfully enough to crush a pine
      board. Subjects in the trained group took a Taekwondo course three times a week
      for 7 mo. This program was designed for the cognitive and physical
      characteristics of mentally retarded persons. After 7 mo., all subjects underwent
      posttests like the pretests. A four-channel EMG analyzing device (LAXTHA Inc.,
      2001) recorded EMG activity. Analysis of co-variance analyzed the difference of
      mean pre- and posttests for the two groups. For premotor RT, mean performance of
      the groups showed no significant difference, but significant improvement in mean
      motor RT by the trained group (p <.01) was noted.

PMID- 15560365
TI  - Adapting a grid into a microswitch to suit simple hand movements of a child with
      profound multiple disabilities.
AB  - We adapted a grid into a microswitch for the hand movements of a girl with
      profound multiple disabilities who lay on her back. The grid, suspended above the
      girl's face, was equipped with two mercury devices, i.e., small sealed ampoules
      containing a mercury drop and ending with conductive leads. A lateral or forward
      movement of the grid would make the mercury drop of at least one device slide to
      the conductive leads and activate the device. During the intervention,
      activations of the devices, i.e., microswitch activations, produced the
      occurrence of favorite stimuli. Analysis showed that the girl increased the
      frequency of hand movements and microswitch activations during the intervention
      phases compared to the baseline phases (when the favorite stimuli were not
      available). The increase was retained at a 1-mo. postintervention check.

PMID- 15560366
TI  - Coaches' assessment of their coaching efficacy compared to athletes' perceptions.
AB  - This study compared coaches' assessments of their own coaching efficacy with
      their athletes' perceptions of the coaches' efficacy. Coaching efficacy was
      measured with the Coaching Efficacy Scale. Participants were 9 football coaches
      and 76 football players from the same team. Analysis indicated coaches were
      confident in their coaching abilities (range 6.5 to 9.0 on a 9-point scale). For
      7 of the 9 coaches the coaches' ratings of themselves were higher than the
      athletes' ratings. For the other 2 coaches, athletes' ratings of coaches'
      efficacy were higher than the coaches' ratings of themselves. All coaches'
      ratings fell within the 95% confidence interval based on the athletes' ratings of
      the coaches' efficacy. Results are discussed in terms of the interplay between
      athletes and coaches efficacy beliefs and its influence on behavior.

PMID- 15560367
TI  - Construct validity of the self-assessment evaluation form for the Olympic
      Education Training Program in Greece.
AB  - The Professional Development Evaluation Form, developed to evaluate training of
      physical education teachers for the Olympic education program in Greece, was
      administered to 438 physical educators (205 men and 233 women; M age=32.2 yr.,
      SD= 9.1). A confirmatory factor analysis indicated an adequate fit of the
      proposed model.

PMID- 15560368
TI  - Cloning, sequencing and partial characterisation of sorbitol transporter (srlT)
      gene encoding phosphotransferase system, glucitol/sorbitol-specific IIBC
      components of Erwinia herbicola ATCC 21998.
AB  - A DNA fragment of approximately 1500 bp, harbouring the sorbitol transport gene
      (srlT), was amplified from the chromosomal DNA of Erwinia herbicola ATCC 21998 by
      PCR and cloned in Escherichia coli JM109. Degenerate oligonucleotide primers used
      were designed based on the conserved regions in the gene sequences within the gut
      operon of E. coli (Gene Bank accession no. J02708) and the srl operon of Erwinia
      amylovora (Gene Bank accession no. Y14603). The cloned DNA fragment was sequenced
      and found to contain an open reading frame of 1473 nucleotides coding for a
      protein of 491 amino acids, corresponding to a mass of 52410 Da. The nucleotide
      sequence of this ORF was highly homologous to that of the gutA gene of
      Escherichia coli gut operon, the srlE gene of Shigella flexrni and the sorbitol
      transporter gene sequence of Escherichia coli K12 (Gene Bank accession nos.
      J02708, AE016987 and D90892 respectively). The protein sequence showed
      significant homology to that of the phosphotransferase system i.e. the
      glucitol/sorbitol-specific IIBC components of Escherichia coli and Erwinia
      amylovora (P56580, O32522). The cloned DNA fragment was introduced into a pRA90
      vector and the recombinant was used for developing srlT mutants of Erwinia
      herbicola, by homologous recombination. Mutants obtained were unable to grow on
      minimal medium with sorbitol. The insertion of the pRA90 vector inside the srlT
      gene sequence of the mutants was confirmed by DNA-DNA hybridisation.

PMID- 15560369
TI  - Stimulation of transcriptional expression of human UDP-glucuronosyltransferase
      1A1 by dexamethasone.
AB  - Human UDP-glucuronosyltransferase (UGT) 1A1 is only enzyme in the conjugation of
      bilirubin for prevention of hyperbilirubinemia and jaundice. Deletion or mutation
      of the UGT1A1 gene causes Crigler-Najjar syndrome or Gilbert's syndrome. We
      previously reported the functional promoter region for expression of UGT1A1
      [Hepatology Research 9, 152-163 (1997)]. We investigated the influence of some
      drugs on the transient transfection assay of the luciferase reporter gene
      containing the 5'-promoter region -3174/+14 of UGT1A1 in HepG2 cells. Among drugs
      investigated, dexamethasone was the most effective at the range of concentration
      of 10-100 microM, whereas stimulation by beta-estradiol was not found. We also
      could not find stimulation by bilirubin of the endogenous main substrate for
      UGT1A1. Stimulation by dexamethasone was continued for 48 hr. The luciferase
      reporter gene containing the 5'-region of -97/+14 was induced by dexamethasone
      but the gene of the 5'-region -53/+14 was not. The region -97/-53 is essential
      for induction by dexamethasone. This region contains HNF1 element, therefore, we
      speculated that dexamethasone directly and/or indirectly stimulates UGT1A1
      expression through this HNF1 region in the promoter region of UGT1A1. Thus, we
      clarified that UGT1A1 was induced by dexamethasone and the key position was the
      region (-97/-53) in UGT1A1 promoter.

PMID- 15560370
TI  - Mammalian apoptosis-inducing protein, HAP, induces bacterial cell death.
AB  - In attempting to produce the HAP, endoplasmic reticulum (ER) targeted apoptosis
      inducing protein, as a GST-fusion protein we found that the expression of HAP,
      but not GST alone, induced bacterial cell death. The HAP protein inhibited the
      bacterial growth within 30 min after inducting HAP expression. The transmission
      electron microscopic examination revealed that the morphology of the bacterial
      cells expressing hap was changed dramatically: unusually elongated phenotype
      compared with those of controls and finally leading to cell death. The lethality
      of HAP was relieved by the addition of vitamin E as a reducing agent and under
      anaerobic growth conditions. These results suggest that a trace amount of HAP
      induces bacterial cell death and the death is related with reactive oxygen
      species (ROS).

PMID- 15560371
TI  - Identification of a cDNA clone encoding DIP1-binding protein in Drosophila
      melanogaster.
AB  - The Drosophila melanogaster L27a gene encodes a ribosomal protein which is a
      member of the L15 family of ribosomal proteins. D.m. L27a is closely related to
      the mammalian protein that has been found differentially expressed in lung cancer
      tissues and therefore could be involved in the control of cell proliferation such
      as the ribosomal protein S6. Our work elucidates the role of DIP1 which is a
      novel protein that we found in Drosophila. We performed a two-hybrid system assay
      and identified the L27a protein as an interactor of DIP1. The interaction was
      then validated by in vitro binding assays. DIP1, similar to other nuclear
      proteins in eukaryotes, is localized to the nuclear periphery and chromatin
      domain in all nuclei, but disappears at the metaphase. It is possible that in
      D.m. L27a protein, via interaction with DIP1, could be involved in protein
      synthesis as well as in cell cycle regulation.

PMID- 15560372
TI  - Characterization of a cDNA encoding a protein with limited similarity to beta1, 3
      N-acetylglucosaminyltransferase.
AB  - Glycosyltransferases constitute a large group of enzymes that are involved in a
      wide range of functions in all living organisms. By large-scale sequencing
      analysis of a human fetal brain cDNA library, we isolated a novel human putative
      glycosyltransferase gene named beta3GnTL1. Its cDNA is 1372 base pair in length,
      encoding a predicted protein with 361 amino acid residues. The human beta3GnTL1
      is located to chromosome 17q25.3 by comparison of its cDNA with human gemome
      database. RT-PCR result shows the beta3GnTL1 is expressed at various levels in
      most of tissues examined.

PMID- 15560373
TI  - The expression of three desaturase genes of Spirulina platensis in Escherichia
      coli DH5alpha. Heterologous expression of Spirulina-desaturase genes.
AB  - The genes from a cyanobacterium--Spirulina platensis strain C1--that encode the
      acyl-lipid desaturases (desC, desA and desD) involved in gamma-linolenic (GLA)
      synthesis have been successfully expressed for the first time in Escherichia coli
      by employing a pTrcHisA expression system. In this report, the authors describe
      the expression of the three Spirulina N-terminal 6xHis-desaturases as well as the
      functional analysis of these recombinant proteins. The gene products of desC,
      desA and desD have approximate molecular masses of 37, 45, and 47 kDa,
      respectively. Enzymatic activity measurement of these products was carried out in
      vivo to demonstrate that (i) the expressed proteins are in functional form, and
      (ii) the cofactors of the host system can complement the system of Spirulina
      platensis. The study demonstrated that the gene products of desC and desA
      catalyzed the reactions in vivo where the enzyme substrates were provided in
      appropriate concentration. This indicates that the delta9 and delta12 desaturases
      were expressed in the heterologous host in their active form, and that these two
      reactions can be carried out in an E. coli host cell using its cofactors system.
      In contrast, delta6 desaturase activity can be detected only in vitro where
      electron carriers are provided. This suggests that while this enzyme is expressed
      in the heterologous host in its active form, its function in vivo is suppressed,
      as the electron carriers of the host system cannot complement the system of
      Spirulina platensis.

PMID- 15560374
TI  - Cloning and characterization of a human cDNA ACAD10 mapped to chromosome 12q24.1.
AB  - Mitochondrial fatty acid beta-oxidation is an important energy resource for many
      mammal tissues. Acyl-CoA dehydrogenases (ACADs) are a family of flavoproteins
      that are involved in the beta-oxidation of the fatty acyl-CoA derivatives.
      Deficiency of these ACADs can cause metabolic disorders including muscle fatigue,
      hypoglycaemia, hepatic lipidosis and so on. By large scale sequencing, we
      identified a cDNA sequence of 3960 base pairs with a typical acyl-CoA
      dehydrogenase function domain. RT-PCR result shows that it is widely expressed in
      human tissues, especially high in liver, kidney, pancreas and spleen. It is
      hypothesized that this is a novel member of ACADs family.

PMID- 15560375
TI  - Molecular cloning and characterization of a novel human protein phosphatase 2C
      cDNA (PP2C epsilon*).
AB  - We have isolated a novel cDNA from the human fetal brain cDNA library with
      homology to the Mg2+ -dependent serine/threonine protein phosphatase 2C (PP2C)
      family. The cDNA is 3055 bp in length, and the predicted coding region encodes a
      360-amino-acid protein, which shows 99% identity to the PP2C epsilon from rat and
      mouse. Then we term it human PP2C epsilon gene. The gene is mapped to chromosome
      3q26.1 and contains 4 exons. RT-PCR analysis shows that the PP2C epsilon is
      widely expressed in human tissues and the expression levels in heart, placenta,
      lung, liver, kidney, and pancreas are relatively high.

PMID- 15560376
TI  - Steps to reduce the risk of falls.

PMID- 15560377
TI  - [Pathogenesis of beta-lactam-resistant Haemophilus influenzae isolated from
      sputum].
AB  - Haemophlus influenzae persists in the respiratory tract and sometimes causes
      respiratory tract infections. To evaluate the pathogenesis of beta-lactam
      resistant Haemophilus influenzae, we classified 193 Haemophilus influenzae
      strains isolated from sputum of patients with respiratory tract disease in 24
      beta-lactamase positive (BLP) strains, 65 beta-lactamase negative ampicillin
      resistant (BLNAR) strains and 104 beta-lactamase negative ampicillin sensitive
      (BLNAS) strains and reviewed the pathogenesis of the strains. The pathogenesis of
      the strains was evaluated as definite pathogen, presumptive pathogen,
      colonization and contamination. It was judged to be the definite pathogen that
      many bacteria isolated from high quality sputum of the patients with respiratory
      tract infections. Presumptive pathogen was considered to be the bacteria provided
      from the patient with respiratory infections when the quality of the sputum or
      quantity of bacteria did not satisfy superscription basis. We considered the
      bacteria to be colonization or contamination isolated from patients without
      infections. The breakdown of definite pathogen/presumptive
      pathogen/colonization/contamination in each by groups was BLP (8/4/8/4), BLNAR
      (26/14/15/10), BLNAS (36/20/31/17). The ratio of definite or presumptive pathogen
      was 50% in BLP, 62% in BLNAR and 54% in BLNAS and the significant difference was
      not recognized in these. Pathogenesis of beta-lactam-resistant Haemophilus
      influenzae is estimated to be equal with beta-lactam-sensitive Haemophilus
      influenzae.

PMID- 15560378
TI  - [The trend of childhood bacterial meningitis in Japan (2000-2002)].
AB  - We surveyed the epidemiology of bacterial meningitis in pediatrics between July
      2000 and December 2002 in Japan and obtained the following results.: The number
      of cases of bacterial meningitis was 316 (182 boys and 134 girls), which was
      equivalent to 1.1-1.7 children out of 1,000 hospitalized those in pediatrics per
      year. The age-distribution for the infections was the highest under 1 year of age
      and it decreased as the age increased. Haemophilus influenzae was the most common
      pathogen causing the infections, followed by Streptococcus pneumoniae, group B
      streptococcus, and Escherichia coli. Relationship between causing pathogens and
      age-distribution was as follows: group B streptococcus and E. coli were major
      pathogens under 4 months of age and H. influenzae and S. pneumoniae were major
      pathogens over 4 months of age. Susceptibility tests performed at each facility
      demonstrated that 53.7% of H. influenzae isolates and 67.7% of S. pneumoniae
      isolates in 2003 were drug-resistant. As ampicillin and cephem antibiotics are
      effective against GBS, E. coli and Listeria at present, then the combination of
      ampicillin and cephem antibiotics was used as first line antibiotics in many
      facilities under 4 month of age and a combination of carbapenem which showed
      effective against PRSP and cephem which showed effective against H. influenzae is
      first choice against childhood bacterial meningitis over 4 month of age.

PMID- 15560379
TI  - [The prevalence of beta-lactamase negative ampicillin resistant Haemophilus
      influenzae in Mie Prefecture].
AB  - Equivalent MIC breakpoints to detect beta-lactamase negative ampicillin resistant
      Haemophilus influenzae (BLNAR) were controversial. We studied the relationship of
      drug resistance with gene alterations in 74 clinical isolates of H. influenzae.
      Out of 74 isolates, 26 showed MIC of ampicillin (ABPC) > or = 1 microg/ml. All
      isolates, except one, with MIC of ABPC > or = 4 microg/ml were found to produce
      beta-lactamase, while all 19 isolates with MIC of ABPC at 1 or 2 microg/ml were
      non-producing. Twenty-six ABPC resistant isolates were subjected to the analysis
      of genes involved in the drug resistance such as pbp3-1 pbp3-2, and TEM by the
      Haemophilus influenzae gene detection kit (Wakunaga Pharmaceutical Co., Ltd.)
      according to the supplier's instructions. Three (21.4%) of 14 beta-lactamase non
      producing isolates with ABPC-MIC of 1 microg/ml had mutations of pbp3-1 gene,
      while all 5 non-producing isolates with ABPC-MIC of 2 microg/ml showed mutations
      of both pbp3-1 and pbp3-2 genes. Accordingly, it seems appropriate to set ABPC
      MIC > or = 2 microg/ml for detection of BLNAR. In this study, six (8.1%) of 74
      isolates were found to be BLNAR, and all of these six isolates were derived from
      patients of 5 year-old or younger.

PMID- 15560380
TI  - [Legionella pneumonia which occurred in a private whirlpool bath user].
AB  - A 88 year old female with active rheumatoid arthritis treated by low dose of
      prednisolone and methotrexate was admitted to our hospital because of severe
      bilateral pulmonary infiltration and acute respiratory distress syndrome. On
      admission, she had consciousness disturbance and was intubated because of severe
      respiratory failure. We heard from her family of her habit she had taking a
      private whirlpool bath 2 or 3 times everyday. So, we suspected a Legionella
      pneumophila infection. We started intravenous erythromycin (EM) (1,500mg/day) and
      methylprednisolone pulse therapy (1,000mg x 3days) and full controlled mechanical
      ventilation supported with PEEP. Her respiratory failure was gradually improved
      and she was discharged on the 44 the hospital day. Legionella pneumophila
      (serogroup 6) was isolated in her sputum by B-CYE alpha culture. Legionella
      pneumophila (serogroup 6) was isolated in her private whirlpool bath too. Both
      samples revealed the same by genetic analysis with pulse field gel
      electrophoresis (PFGE). This is the first adult case of Legionella pneumophila
      pneumonia infected from a private whirlpool bath confirmed by genetic analysis.
      We should always suspect Legionella pneumonia as one of the severe community
      acquired pneumonia, because Legionella pneumophila were frequently detected among
      various water sources including the private whirlpool bath.

PMID- 15560381
TI  - [A case of pseudomembranous enterocolitis caused by methicillin-resistant
      Staphylococcus aureus].
AB  - A 47-year-old woman was hospitalized because of urinary-tract infection. She was
      treated with antibiotics for 6 days. However, severe watery diarrhea and pyrexia
      developed 6 days after stopping administration of antibiotics. Stool, throat and
      blood cultures were positive for methicillin-resistant Staphylococcus aureus
      (MRSA) and negative for Clostridium difficile DI toxin. In spite of
      administration of VCM, she died of septic shock. At autopsy, macroscopic
      observation revealed a pseudomembrane in the ileum. MRSA enterocolitis can occur
      in patients with antibiotic-related diarrhea, and physicians should be aware of
      its rapid clinical course and possible lethal outcome.

PMID- 15560382
TI  - [A case of primary pulmonary cryptococcosis showing lobar pneumonia on chest X
      ray].
AB  - A 36-year-old male who had been in good health visited our hospital because of
      fever, productive cough and lobar pneumonia of the right lower lobe.
      Bronchoscopic examination revealed pulmonary cryptococcosis. After the initiation
      of fluconazole the pneumonia started to improve, however, it was aggravated after
      the discontinuation of fluconazole because of liver dysfunction induced by it.
      The pulmonary cryptococcosis improved by lobectomy of the right lower lobe. There
      have been few reports of lobar pneumonia caused by primary pulmonary
      cryptococcosis. We report this case with fourteen other cases of primary
      pulmonary cryptococcosis which have been experienced in our hospital.

PMID- 15560383
TI  - [A case of a young woman with tuberculous peritonitis diagnosed owing to high
      value of ADA].
AB  - A 26-year-old woman visited the first hospital due to ascites in August 2003, She
      had continual abdominal pain diagnosed as Irritable bowel disease after a
      gastrointestinal and colon fiberscopy was performed. Chest-abdominal CT scan
      revealed normal chest, massive ascites and swollen ovary. To rule out malignancy,
      surgical biopsy was performed, which brought no significant findings. We focused
      on the high value of Adenosin deaminase (ADA) in ascites and strongly suspected
      tuberculotic peritonitis. Consequently, pathologist confirmed the existence of
      bacterial bodies stained by acid-fast stain after our consultation. Compared with
      the poor diagnostic accuracy of surgical biopsy, the value of ADA in ascites has
      a very high sensitivity and specificity. Considering the high risk of being
      infertile, to begin diagnostic medication of tuberculotic peritonitis is an
      acceptable choice for young women with a high value of ADA in the ascites.

PMID- 15560385
TI  - [Novel experience].

PMID- 15560384
TI  - [Virulence evaluation of Legionella pneumophila environmental isolates by using
      the amoeba-agar method].

PMID- 15560386
TI  - [Efficacy of lidocaine on seizures by intravenous and intravenous-drip infusion].
AB  - We retrospectively studied the efficacy of intravenous and intravenous-drip
      infusion administration of lidocaine on seizures treated in Saitama Children's
      Medical Center during the period of 1997-2002. Thirty eight seizures of 29
      children (12 boys and 17 girls, average age 41.4 months) were treated with
      lidocaine. The overall rate of effectiveness was 53%. The response to lidocaine
      appeared within 5 minutes in all episodes. Good response to lidocaine was noted,
      in 36% of patients with epilepsy, in 72% with CNS infection and in 80% with
      benign infantile convulsions; in 42% with generalized seizures and in 63% with
      partial seizures. Thus there was no significant difference in efficacy among the
      underlying disorders and seizure types. The adverse reaction of SpO2 decrease was
      found in one patient. We conclude that lidocaine can be used as a second-line,
      anti-convulsive drug in status epilepticus based on its prompt effectiveness and
      low risk of side effects.

PMID- 15560387
TI  - [Effects of tizanidine for refractory sleep disturbance in disabled children with
      spastic quadriplegia].
AB  - Tizanidine is a centrally acting alpha-2 adrenoreceptor agonist widely used in
      the treatment of spasticity in patients with cerebral or spinal injury, and it is
      causing drawsiness in some of them. Based on these drug actions, we administered
      tizanidine to 21 spastic quadriplegic children with severe sleep disturbance not
      improved by conventional therapies. All these patients were showing abnormalities
      of both the induction and maintenance of sleep. The dosage of tizanidine was 0.1
      to 0.2 mg/kg/day, divided into two or three doses. If daytime drowsiness was
      severe, tizanidine admistration was restricted to just prior to bedtime. In 13
      patients (61.9%), we found improvement in sleep induction and/or maintenance.
      Moreover, patients' families were satisfied with the treatment. There were no
      detectable side effects except facial pallor in two patients (9.5%) whose
      treatment was discontinued. Severe muscle hypertonia causes severe pain, which
      generates strong sympathetic nerve activity and subsequent sleep disturbance. We
      consider that tizanidine has direct effects on the induction of sleep, and
      promotes muscular relaxation bringing about good sleep. We conclude that
      tizanidine is useful for the treatment of refractory sleep disturbance in spastic
      quadriplegic patients.

PMID- 15560388
TI  - [Bell's palsy in children: analysis of clinical findings and course].
AB  - To evaluate treatment of Bell's palsy (acute idiopathic peripheral facial nerve
      paralysis) of children, the authors analyzed 38 cases (18 females, 20 males) of
      Bell's palsy in children aged below 16 years old. The mean age of all cases was
      6.8 +/- 6.2 years old. All cases resulted in complete recovery within 6 months.
      Clinical score of facial motor functions were adapted to 17 patients who were
      more than 5 years old. They were divided into two groups: early recovery group
      (clinical symptoms recovered within 3 months; 10 cases) and later recover group
      (over 3 months; 7 cases). Clinical scores evaluated in the first week from the
      onset were not significantly different. Steroid therapy was used for 9 patients
      of early group and 6 patient of later group. All patients of this study were
      recovered, thus we could not evaluate effect of steroid therapy for Bell's palsy
      in children. Use of steroid therapy for Bell's palsy needs more concretely
      administration. We consider how the region locates near to the center is an
      important prognostic factor.

PMID- 15560389
TI  - [Impulsive behaviors in attention-deficit/hyperactivity disorder].
AB  - The notion that difficulty in behavioral inhibition is the essential impairment
      of attention-deficit/hyperactivity disorder (AD/HD) has been prevailing. In this
      study, we assessed impulsive behaviors with regard to emotion, rule, and
      inattentiveness, by developing an impulsiveness scale and applying it for 103
      parents of a boy with AD/HD. Exploratory factor analysis (EFA) of 18 items
      identified four primary factors: labeled emotion expression, social rule, rule in
      conversation, and inattentiveness. A covariance structural analysis was performed
      to extract response bias from latent constructs, and the fitness of the model was
      examined. In the finally adopted model on impulsive behaviors, the four factors
      extracted in EFA was explained by two independent second-order latent variables:
      labeled general impulsivity and cognitive impairment. Cognitive impairment
      significantly influenced on inattentiveness only, while general impulsivity on
      all the four factors. Furthermore, the scores of primary four factors were
      compared between two groups of a normal class group (n = 20) and three AD/HD
      subtypes:combined type (n = 37), predominantly hyperactive-impulsive type (n =
      14), and predominantly inattentive type (n = 18). The results suggest differences
      in impulsive behaviors among the AD/HD subtypes.

PMID- 15560390
TI  - [Effect of development and aging on the modified Wisconsin Card Sorting Test in
      normal subjects].
AB  - The Wisconsin card sorting test (WCST) is applied to various types of
      neurological disorders. Since WCST requires the examinee's sustained efforts, it
      is not readily applicable to children with developmental disorders. In order to
      overcome this weakness, Keio version WCST (KWCST) was developed by reducing the
      number of cards from 128 to 48 and presenting them in two steps separated by a
      short pause. During which a brief instruction was given. This study was performed
      to clarify the changes with age in indices of KWCST and to obtain the normative
      value. Three hundred thirty five normal subjects, ranging from 5 to 82 years of
      age were examined. A simple regression analysis showed a significant age-related
      changes. Subjects between the middle thirties and the middle forties showed the
      best score in such indices as the categories achieved, perseverative errors of
      Nelson, difficulties of maintaining set, numbers of response cards until the
      first category achieved, and total errors. Most of the scores were improved in
      the second step across the all age groups, which might have resulted from
      learning during the first step and the instruction provided before the second
      step. KWCST can be performed briefly, and is suitable for cases with attention
      deficit/hyperactivity disorder and pervasive developmental disorder.

PMID- 15560391
TI  - [Quantitative study of brain perfusion patterns of 99mTc-ECD SPECT in children
      with developmental disabilities].
AB  - The aim of this study was to investigate the relationship between developmental
      disabilities and brain perfusion patterns. We performed technetium-99 m
      ethylcysteinate dimer (99m-Tc-ECD) single photon emission computed tomography
      (SPECT) in 30 children with neurological disorders using the Patlak plot method.
      In children without developmental disabilities, the distribution of regional
      cortical perfusion evolved in relation to brain maturation. At one month of age,
      there was a predominant uptake in the perirolandic cortex. Radionuclide uptake in
      both the parietal and occipital cortices became evident by three months. Uptake
      in the temporal and frontal cortex increased by 6 and 11 months, respectively.
      Brain perfusion showed a pattern similar to that of adults by two years of age at
      the latest. In children with developmental disabilities, developmental changes of
      brain perfusion were delayed compared to normally developing children. Brain
      SPECT is a useful tool to assess the brain maturation in children with
      developmental disabilities.

PMID- 15560392
TI  - [Two cases of acute encephalitis/encephalopathy associated with adenovirus type 3
      infection].
AB  - Although adenovirus type 3 is a common pathogen of pediatric infection, there
      have been few reports on encephalitis and encephalopathy caused by this virus. We
      report two cases, one of acute encephalitis and another of transient
      encephalopathy, associated with adenovirus type 3 infection. Case 1, an 11-year
      old boy with unconsciousness and convulsions, was diagnosed as having acute
      encephalitis because adenovirus type 3 was isolated from the cerebrospinal fluid.
      Case 2, a 3-year-old boy with intermittent excitement and hallucinations, was
      diagnosed as having transient encephalopathy. MRI, EEG, and cerebrospinal fluid
      studies were normal. Our cases and previously reported cases exhibit a wide
      clinico-pathological spectrum of the central nervous system involvement by
      adenovirus type 3.

PMID- 15560393
TI  - [Report on the IV Congress of the Russian Scientific Society of
      Gastroenterologists].

PMID- 15560394
TI  - [Selecting variants of drug treatment of non-complicated duodenal ulcer (based on
      a study of results of Rabeprazole efficiency)].
AB  - This article presents considerations currently under discussion about the
      probability of HP participation in the ulcer causation as well as information
      about Rabeprazole efficiency for anti-helicobacter therapy of non-complicated
      duodenal ulcer (as a result of 7-day anti-helicobacter therapy, the healing of
      duodenal bulbs was recorded in 82.6% of cases; HP eradication was recorded in
      86.9% of cases 4 weeks after the termination of the treatment) based on the
      analysis of scientific literature data and personal experience. Considerations
      related to the conduction of a possible study in the field of ulcer therapy that
      is not associated with Helicobacter pylori are presented.

PMID- 15560395
TI  - [The impact of the degree of Helicobacter pylori semination of the mucous coat of
      stomach in patients with duodenal ulcer on the infectious organism's
      eradication].
AB  - The purpose of the study is to discover the dependence of results of HP
      eradication with standard triple schemes on the degree of HP semination of the
      mucous coat of stomach in patients with duodenal ulcer.

PMID- 15560396
TI  - [A study of the immunological status in patients with stomach ulcer during acute
      conditions and remission].
AB  - The interest shown in the functioning of the immunity system at ulcer is mainly
      stipulated by newly emerged methods of diagnosing and treating patients, which
      have broadened our insight into the pathogenesis of the disease. The study of the
      nature of immunological improvements observed in the peripheral blood of patients
      with stomach ulcer enables us to find a differential approach to the correction
      of the inflammatory process.

PMID- 15560397
TI  - [A study of the condition of parodentium in patients with stomach and duodenal
      ulcer].
AB  - The objective of this research was a study of the condition of parodentium
      tissues in patients with ulcer. 51 ulcer patients were studied. As a result of
      complex studies (hemorrhage coefficient, crevicular liquid, papilloalveolar
      marginal index, complex periodontal index and thermometry), apparent inflammatory
      processes were discovered in parodentium tissues. Inflammatory parodentium
      changes do not disappear completely with the complex anti-ulcer therapy that
      forms a basis for the simultaneous application of local therapeutic measures to
      eliminate inflammatory processes in parodentium tissues.

PMID- 15560398
TI  - [Prevalence of celiac disease in patients with chronic diarrhea].
AB  - The objective of this research was to study the frequency of celiac disease in
      patients with chronic diarrhea. The biopsy materials of the small intestine and
      levels of antibodies to alpha-gliadin of class A immunoglobulins (IgA) and tissue
      transglutaminase were studied in 206 patients with chronic diarrhea. Morphologic
      celiac-specific symptoms were discovered in 35 (16.9%) patients. Symptoms of the
      total atrophy were discovered in 28 patients (13.5%); those of subtotal one were
      found in 7 (3.4%) patients. The increase of antibody levels to IgA alpha-gliadin
      and tissue transglutaminase was discovered in all 35 patients. Their average
      level made up 123.7 21.2 units per milliliter and 48.7 11.3 units per milliliter,
      respectively. It was possible to observe the typical celiac form only in 4
      (11.4%) patients; the latent form was found in 30 (85.7%) patients, and the
      torpid (refractory) form was discovered in 1 (2.8%) patient. The frequency of
      celiac disease in patients with chronic diarrhea is equal to 16.9%. Patients with
      the latent form of the disease prevail among patients with celiac disease.
      Immunological screenings with the subsequent morphologic study of the mucous coat
      of the small intestine should be prescribed to all patients with the chronic
      diarrhea syndrome to enable the early diagnostics of celiac disease.

PMID- 15560399
TI  - [Application of Mesim Forte 10000 at chronic pancreatitis].
AB  - There was a study of 30 patients with chronic pancreatitis (CP) to study the
      efficiency of action of Mesim Forte 10000 on the functional state of the pancreas
      and liver at chronic pancreatitis. Patients were given two pills of the drug
      three times a day during three weeks. The pancreatic elastase and contents of
      short chain fatty acids in excrements as well as blood concentration of
      individual fractions of bile acids were investigated before and after the
      treatment. According to this research, such clinical presentations of CP as pain
      syndrome, meteorism and stool frequency were greatly reduced as a result of the
      therapy with the enzymatic drug Mesim Forte 10000. The increase of the level of
      the pancreatic elastase depending on the severity of exocrine pancreatic
      deficiency was determined. At the same time, it was possible to observe the
      correction of a number of biochemical processes in the gastrointestinal tract
      related to the exocrine deficiency. In particular, the treatment of the greater
      part of steatorrhea patients with Mesim Forte 10000 led to apparent changes in
      the metabolic activity of bacterial microflora resulting in the improvement of
      the quantity and quality of fatty acids.

PMID- 15560400
TI  - [Proton pump inhibitors as the basis of anti-helicobacter therapeutic schemes].

PMID- 15560401
TI  - [Some comparative aspects of treating the gastroesophageal reflux disease
      eradication].
AB  - At present proton pump inhibitors have been the most efficient drugs for treating
      the gastroesophageal reflux disease (GERD). Pariet may be selected as a drug for
      treating all forms of GERD as it requires smaller doses and shorter treatment
      period to obtain the clinical and endoscopic remission. Upon the clinical and
      endoscopic remission, patients need a supportive treatment. Different patients
      need various supportive treatment schemes. Our goal comes to the provision of the
      maximum efficiency of the schemes when prescribing the minimum doses of the drug.

PMID- 15560402
TI  - [Endoscopic preventive metabolic hemo- and homeostasis in the treatment of
      ulcerous gastroduodenal bleedings complicated with a severe blood loss and
      hemorrhagic shock].

PMID- 15560403
TI  - [A comparative assessment of the life quality of patients after various surgeries
      because of complicated duodenal ulcer].
AB  - Showings of studying the life quality with the aid of the SF-36 questionnaire can
      be used for assessing long-term results of various types of surgeries at
      complicated duodenal ulcer. Unlike stomach resections, functional surgeries
      provide a higher life quality of patients. Such differences become more apparent
      as time after the surgery passes by.

PMID- 15560404
TI  - [The impact of the type of anesthesia on stress-realizing and stress-limiting
      mechanisms of the immune system in gerontological patients at abdominal
      surgeries].
AB  - Surgical stress resulting from the operative morbidity and narcosis aggravates
      the associated age-related and secondary immunodeficiency of gerontological
      patients at surgeries. Stress hormones have a strong depressing effect on the
      immunity by forming stress immunodeficiency. Not only high blood level determines
      the damaging effect of stress hormones but also the activity of stress-limiting
      mechanisms of the immune system protect it from the damaging effect of stress
      hormones. In this connection, the impact of operative morbidity and anesthetic
      aggression on the activity of stress-realizing and, in particular, stress
      limiting mechanisms plays an important role because of the frequency of
      postoperative complications in gerontological patients namely. We observed
      patients operated on the abdominal cavity by urgent indications with a delay or
      based on a schedule under conditions of epidural anesthesia (45 patients), spinal
      anesthesia (43 patients) and general anesthesia (41 patients). The analysis of
      data obtained shows that different types of anesthesia have different effect on
      the plasmic cortisol level and activity of stress-realizing and stress-limiting
      systems. Thus, in case of epidural anesthesia of gerontological patients it was
      possible to observe the reduction of the high plasmic cortisol level and
      activation of stress-limiting reception of immunocompetent cells contributing to
      the preservation of the immune function. The increased plasmic cortisol level
      accompanied spinal anesthesia applied to such patients. However, it did not
      suppress the stress-limiting reception protecting the immunity against the
      damaging action of cortisol. In case of general anesthesia of gerontological
      patients it was possible to observe the increased blood cortisol level and
      decreased activity of protective stress-limiting receptors contributing to the
      formation of glucocorticoid immunosuppression.

PMID- 15560405
TI  - [Results of the portacaval shunting and suturing of esophageal and stomach
      varicose veins in patients with cirrhosis and portal hypertension (a comparative
      study)].

PMID- 15560406
TI  - [Gradient of serotonergic innervation of internal organs].
AB  - The unidirectional synergistic effect of the vegetative nervous system
      departments was studied at the regulation of the activity of internal organs. It
      was shown that the sympathetic nerve intensification of the vagal stimulation of
      EMA of stomach, urinary bladder, ureters, uteruss, fallopian tubes and deferent
      duct is realized by means of activation of serotonergic fibrae preganglionares
      that transmit the activation to 5-NTS,4 serotonin receptors of intramural ganglia
      that, in their turn, activate 5-NT1,2 serotonin receptors of effector cells.

PMID- 15560407
TI  - [Modern myths of clinical gastroenterology].
AB  - The appropriateness of further wide prevalence of diagnostics of gastroesophageal
      reflux disease, functional non-ulcer dyspepsia and irritable bowel syndrome is
      discussed. All these diseases are believed to be found in 30-50% of adults. It is
      very difficult to find a healthy person taking into account such an approach to
      the problem. As a matter of fact, gastroesophageal disease was invented by
      merging two different diseases: esophagitis and reflux esophagitis plus such a
      prevalent symptom as heartburn. All this leads to the hyperdiagnosis of this
      disease. The irritable bowel syndrome also includes two conditions: that of the
      irritable large intestine and dyskinesia of the small one. They are very
      different. The application of the diagnosis of functional dyspepsia leads to the
      practical disappearance of the diagnosis of chronic gastritis. At that symptoms
      of the dyskinetic form of functional dyspepsia coincide with minor symptoms of
      gastric carcinoma, which can lead to late diagnostics of this oncological
      disease. In this connection, it is necessary to narrow the limits of these
      diseases because their actual prevalence is much lower than that found in medical
      literature.

PMID- 15560408
TI  - [Biliary deficiency and disorders of duodenal digestion].

PMID- 15560409
TI  - Probiotics and mechanisms of their curative action.
AB  - Information about probiotics used for the correction of resident normal colon
      microflora and mechanism of their positive therapeutic actions are presented.
      Probiotics are drugs containing live microbes or substances of microbial origin
      that, when introduced by natural methods, are expected to confer beneficial
      physiologic, biochemical and immune effects to the host through the stabilization
      and optimization of functions of normal microflora. Probiotics containing the
      Bifidobacterium, Lactobacillus, Escherichia, Enterococcus, Asporogenic aerobe
      Bacillus and Saccharomyces boulardii microorganisms are characterized.

PMID- 15560410
TI  - [Some problems of the operated stomach related to the infection of Helicobacter
      pylori].

PMID- 15560411
TI  - The etiology of risk: a preliminary model.
AB  - The purpose of this paper is to describe an approach that links risk-assessment
      and theory-directed research. Here we describe a theoretical underpinning to
      current notions of dynamic risk assessment. The paper has two facets. First, the
      reframing of a number of concepts such as (i). Stable dynamic factors that we
      note would be better described as traits and hence have a grounding in the extant
      general psychological literature on trait theory, (ii). Static risk factors that
      can be viewed as historical markers of the same underlying psychological
      dispositions measured by stable dynamic risk factors; (iii). Acute risk factors
      that are better described as triggering/contextual risk factors (iv). Acute risk
      factors that should be defined as the state expression of traits triggered by
      triggering/contextual risk factors. And second, the description of an etiological
      model of risk- model taking into account the interaction between significant
      learning events (i.e., developmental variables), psychological vulnerabilities
      (i.e., marked by static/historical variables and/or stable dynamic risk factors),
      contextual or triggering factors and their convergence in offense-related acute
      dynamic risk (i.e., acute psychological states).

PMID- 15560412
TI  - Onset, persistence, and versatility of offending among adult males convicted of
      sexual offenses against children.
AB  - Official sexual and nonsexual offense histories and confidential self-report data
      on sexual offending were obtained on 207 adult males serving sentences for sexual
      offenses against children (98 intrafamilial, 72 extrafamilial, and 37 mixed-type
      offenders). The mean self-reported age when offenders first had sexual contact
      with a child was 32.2 years (median = 31 years; range = 10-63 years). The mean
      age at first conviction for any offense was 30.5 years (median = 27 years, range
      = 12-66 years), and the mean age at first conviction for a sexual offense was
      37.3 years (median = 37 years; range = 15-76 years). Sixty-nine percent (n = 143)
      of the combined sample had at least one previous conviction, and 80% of these (n
      = 114) had first been convicted for a nonsexual offense. ANCOVA revealed a
      systematic pattern of onset with first convictions for any offense preceding
      first sexual contact with a child. Taken together, results indicate that, in
      general, adult child molesters (a) begin sexual offending in their 30s, (b) have
      already become involved in nonsexual crime by the time they first have sexual
      contact with a child, (c) are criminally versatile, and (d) vary considerably in
      their persistence with respect to both sexual and nonsexual offending.

PMID- 15560413
TI  - The implicit theories of rapists: what convicted offenders tell us.
AB  - Twenty years of research into sex offenders' cognitive distortions has primarily
      focused on the measurement of distortions rather than on theorizing about the
      underlying structures that are responsible for generating and organizing them.
      Recently T. Ward (2000; T. Ward & T. Keenan, 1999) suggested that offenders have
      underlying causal theories about themselves, their victims, and broader
      categories of people (e.g., women and children), and that these implicit theories
      enable post hoc explanation as well as prediction of people's actions and
      reactions. D. L. L. Polaschek and T. Ward (2002) examined rape-related
      attitudinal scales and constructed and outlined five core implicit theories.
      Here, we examined whether evidence for these five theories was also found in
      offense process descriptions generated from interviews with 37 imprisoned
      rapists. Coding of the descriptions revealed support for all five theories.

PMID- 15560414
TI  - The content of sexual fantasies for sexual offenders.
AB  - Although the phenomenon of sexual fantasy has been extensively researched, little
      contemporary inquiry has investigated the content of sexual fantasy within the
      context of sexual offending. In this study, a qualitative analysis was used to
      develop a descriptive model of the phenomena of sexual fantasy during the offence
      process. Twenty-four adult males convicted of sexual offences provided detailed
      retrospective descriptions of their thoughts, emotions, and behaviors before,
      during, and after their offences. Using Grounded Theory, a model was developed to
      elucidate the content and themes of sexual fantasy for sexual offenders, as well
      as the way fantasy content was used in the process of sexual offending. The
      Sexual Fantasy Content Model (SFCM) comprises of three higher-order (level 1) and
      five second-order (level 2) categories that describe the content of sexual
      fantasy across the offence process. The level 1 categories are general sexual
      fantasy, nonspecific offence fantasy, and offence-specific fantasy, whereas the
      level 2 categories included demographic, behavioral, relational, situational, and
      self-perceptual considerations. The strengths of the SFCM are discussed and its
      clinical implications are reviewed.

PMID- 15560415
TI  - Implicit cognitive distortions and sexual offending.
AB  - This work develops and tests the semantic-motivation hypothesis of sexual
      offenders' implicit cognitions. This hypothesis posits that sexual offenders'
      cognitive distortions emerge at the interface between implicit motivation and
      cognition. The semantic-motivation hypothesis is used to guide the development of
      3 implicit association tests (IATs). These IATs were used to test for the
      existence of 3 expected child sexual offender implicit cognitive distortions in
      child sexual offenders ("children as sexual beings," "uncontrollability of
      sexuality," and "sexual entitlement-bias"). Results showed that child sexual
      offenders had larger IAT effects than did mainstream offenders and male and
      female nonoffenders for the "children as sexual beings" and the
      "uncontrollability of sexuality" implicit theories. Child sexual offenders also
      had a larger IAT effect than male and female nonoffenders for the "sexual
      entitlement-bias" implicit theory. Implications for the semantic-motivation
      hypothesis are discussed.

PMID- 15560416
TI  - Therapeutic jurisprudence and sex offenders: a psycho-legal approach to
      protection.
AB  - Societal response to sex offenders is marked by uncertainty about whether
      punishment or treatment should occur. The distinction between punishment,
      prevention, and protection is useful to determine how best to assess, treat, and
      manage sex offenders within the criminal justice system. Once convicted, both law
      and psychology are concerned with sex offenders changing their behavior in order
      to protect the community. Therapeutic jurisprudence is a legal theory that aims
      to maximize therapeutic effects of the law and minimize anti-therapeutic
      consequences of the law. Therapeutic jurisprudence provides a framework to
      combine legal and psychological processes to balance prevention and protection.
      Legal and correctional practitioners can work together to address both community
      protection and offender protection concerns.

PMID- 15560417
TI  - Reflexivity, reflection, and the change process in offender work.
AB  - This study explores the therapeutic engagement experiences of men who have
      sexually offended against children and who are involved in a prototypical prison
      based group treatment programme. The study examined factors relating to the
      therapeutic engagement of the offender in treatment, and in particular, the
      impact of the "out-of-group" time between sessions. The findings, although
      tentative, suggest that between formal therapy sessions, clients of the programme
      make significant movement either toward or away from engagement in the therapy.
      The implications of these processes with respect to clinical practice and the
      development of offender services are discussed.

PMID- 15560418
TI  - Sex offenders with an intellectual disability.
AB  - It is only in recent years that the myth of the incorrigible and untreatable sex
      offender with an intellectual disability has been seriously questioned. Current
      assessment and treatment approaches in this area assume that such offenders are
      accountable for their actions and treatable with appropriately modified
      techniques. Even though they may be initially hard to engage in the assessment
      and treatment process, the use of simplified approaches that support the day-to
      day reinforcement of treatment concepts is proving to be effective with this
      population.

PMID- 15560419
TI  - Implementation of new requirement under National Patient Safety Goal 3.

PMID- 15560421
TI  - Corrections to 2005 requirements for hospitals.

PMID- 15560422
TI  - Results of advisory panel on USP Chapter 797.

PMID- 15560423
TI  - Modifications to compliance data tables for 2003 National Patient Safety Goals.

PMID- 15560424
TI  - Privatization of Medicare: toward disentitlement and betrayal of a social
      contract.
AB  - An intense political battle is being waged over the future of U.S. Medicare. The
      40-year social contract established with the nation's elderly and disabled is
      seriously threatened. The basic issue is whether Medicare will remain a universal
      entitlement program or be privatized and dismantled as an obligation of
      government. Faced with the growing costs of the Medicare program, changing
      demographics of an aging population, and long-term federal deficits, conservative
      interests are promoting further privatization of the program under the guise of
      increasing beneficiaries' choice and the claimed efficiency of the private
      marketplace. Following a historical overview of past efforts to privatize
      Medicare, this article reviews the track record of private Medicare plans over
      the last 20 years with regard to choice, reliability, cost containment, benefits,
      quality of care, efficiency, public satisfaction, and fraud. In all of these
      areas, privatized Medicare has performed less well than original Medicare. Based
      on the evidence, one has to conclude that privatization of Medicare is
      detrimental to the elderly and disabled, the most vulnerable groups in our
      society, and that the only winners in that transformation are private market
      interests.

PMID- 15560425
TI  - The warp of evidence-based medicine: lessons from Dutch maternity care.
AB  - Most critiques of evidence-based medicine (EBM) focus on the scientific
      shortcomings of the technique. Social scientists are more likely to criticize EBM
      for its ideological biases, a criticism that makes sociological sense but is
      difficult to substantiate. Using evidence from the scientific debate over
      maternity care in the Netherlands--where nearly one-third of births take place at
      home--the author shows that research evidence is the product of a researcher's
      assumptions about the practice in question. In the case of maternity care in the
      Netherlands, ideological differences about the most appropriate way to give birth
      -based in the researcher's clinical experience--give rise to irresolvable
      disagreements about what constitutes evidence and how that evidence is to be
      interpreted. "Evidence" cannot settle scientific disputes in any simple way.
      Rather, it becomes a rhetorical justification for whatever particular groups were
      going to do anyway. Scientific evidence rests on clinical practice, which in turn
      is rooted in structural arrangements and cultural ideas.

PMID- 15560426
TI  - Public involvement in breast cancer research: an analysis and model for future
      research.
AB  - Public involvement in health program planning has been taking place for many
      years, and has provided a precedent for the emergence of public involvement in
      research conducted since the early 1990s. Such involvement is now widely seen in
      breast cancer research, due to the large public concern and major social movement
      activity. This article reviews current practices and general models of public
      involvement in research and constructs a prototype. The authors interviewed
      researchers, program officers, and laypeople in order to understand the
      obstacles, processes, and benefits. They conclude that public involvement has
      major ramifications for the democratization of science and the construction of
      knowledge by teaching lay people about science and sensitizing researchers to
      concerns of the public. There is growing support on the part of scientists and
      government agents for public involvement.

PMID- 15560427
TI  - Recent irregularities in Table II of Morbidity and Mortality Weekly Report.
AB  - Table II of Morbidity and Mortality Weekly Report each week displays the
      cumulative year-to-date provisional number of cases of selected notifiable
      diseases in the United States, by state. Thus comparisons between the same weeks
      for different years can allow a rough rapid tracking of trends. In recent years,
      particularly 2004, the reported provisional cases showed incongruities. As of
      April 16, 2004, for example, no AIDS cases at all appeared in Table II. Responses
      from government public health officials (Centers for Disease Control and
      Prevention (CDC) and State of California) indicate instabilities and problems in
      the public health surveillance and reporting system. Such instabilities and
      problems, if serious and enduring enough, could impair detection of threats to
      public health.

PMID- 15560428
TI  - Harmonization, regulation, and trade: interactions in the pharmaceutical field.
AB  - This article aims to draw attention to the process of harmonization of
      requirements for drug registration (the so-called ICH process) and to examine how
      it may affect access to medicines in developing countries. The ICH process,
      especially when seen in conjunction with the World Trade Organization's Agreement
      on Technical Barriers to Trade, may create additional barriers to would-be
      entrants on the global pharmaceutical market, notably large generic manufacturers
      in developing countries-the very companies that can create credible price
      competition for the innovative industry and, thus, increase access to medicines.
      These barriers could help maintain the status quo by insulating well-established
      companies from competition, thereby forming a further obstacle to lower drug
      prices and to access to medicines, especially in developing countries. Developing
      countries should therefore carefully consider the implications of the positioning
      of ICH standards as global standards, and be vigilant with regard to their
      possible incorporation, whether explicitly or not, in international trade
      agreements.

PMID- 15560429
TI  - Double standards: the multinational asbestos industry and asbestos-related
      disease in South Africa.
AB  - This study documents and contrasts the development of knowledge about asbestos
      related disease (ARD) in South Africa and the United Kingdom. It also contributes
      to the globalization debate by exploring corporate decision-making in a
      multinational industry. Between the 1930s and 1960s, the leading U.K. asbestos
      companies developed a sophisticated knowledge of ARD, though in South Africa,
      where the leading companies such as Turner & Newall and Cape Asbestos owned
      mines, there was little attempt to apply this knowledge. Asbestos mines (and
      their environments) in South Africa were uniquely dusty and ARD was rife. Social
      and political factors in South Africa, especially apartheid, allowed these
      companies to apply double standards, even after 1960 when the much more serious
      hazard of mesothelioma was identified. This shows the need for greater regulation
      of multinationals. Because of the lack of such regulation in the early 1960s, an
      opportunity was lost to prevent the current high morbidity and mortality of ARD
      both in South Africa and worldwide.

PMID- 15560430
TI  - Decentralization of health services: the Kerala People's Campaign.
AB  - The 1996-2001 Kerala People's Campaign for Decentralized Planning has provided
      much new information about the possibilities and potential of decentralizing
      public health and health care services. Analysis of investment patterns of the
      various government levels involved in the campaign, supplemented with case study
      materials, allows for an evaluation of the decentralization project against its
      own stated goals. These included (1) creating a functional division among
      government levels appropriate to the health tasks each level can best perform;
      (2) generating projects that reflect the felt needs of the people, as voiced
      through local participatory assemblies; (3) maintaining or increasing levels of
      equality in health, especially with regard to income, caste, and gender; (4)
      stimulating communities to mobilize voluntary resources to supplement devolved
      public funds; (5) stimulating communities to create innovative programs that
      could become models for others; and (6) making the health services function more
      effectively overall. The analysis supports the conclusion that the campaign
      achieved each of the goals to a large degree. Shortcomings arose from the
      inexperience of many local communities in drafting effective projects as well as
      problems deriving from the fact that some sections of the health bureaucracy
      could not be decentralized. Lessons of the campaign are already being applied to
      new programs in Kerala.

PMID- 15560431
TI  - A case for government ownership of primary care services in New Zealand: weighing
      the arguments.
AB  - Primary care services provide continuing and coordinating care, cater to most
      health care needs, and serve as a point of first contact with the health system.
      This article addresses the issue of government ownership of primary care.
      Ownership confers governance responsibility (ultimate control) for an
      organization, and accountability for its actions. Primary care organizations can
      be classed as government owned and operated or privately owned and operated, the
      latter with or without community governance. The authors address two policy
      questions: Does the ownership form of a primary care organization matter? What
      ownership frameworks should be used to guide policymaking? Arguments for and
      against government ownership are examined from political and economic
      perspectives, informed by a governance framework. Government ownership of primary
      care may solve problems associated with private for-profit ownership that are
      related to lack of control of strategic assets, lack of direct political
      accountability, contracting, and market failure, but it may raise potential
      problems of lack of responsiveness to minority and local needs and capture by
      interest groups. In response to the problems associated with government
      ownership, community-governed private nonprofits have an essential role as a
      vehicle for indigenous self-determination, catering for minority populations,
      experimenting with policy options, and providing public goods particularly for
      minority populations. The authors argue that private organizations that lack
      community governance have a lesser role.

PMID- 15560432
TI  - A review of data on the U.S. health sector: March 2004.
AB  - This report presents information on the U.S. health sector in early 2004. It
      provides data on the insured and uninsured and their access to health care; the
      increasing costs of care; the increasing social and economic inequalities in
      health and health care; and the role of corporate money in health care. The
      author then presents data on the recently passed Medicare prescription drug bill
      and some updates on Medicare HMOs. The article also includes updates on state
      legislative action, recent opinion polls on health care conducted among
      physicians and the general public, and health plans proposed by the presidential
      candidates (as of early 2004).

PMID- 15560433
TI  - The Sachs report: Investing in Health for Economic Development--or increasing the
      size of the crumbs from the rich man's table? Part I.
AB  - The Commission on Macroeconomics and Health report (Sachs report) of 2001 has
      been heralded as inspiring and groundbreaking and is being adopted as the
      blueprint for global health policymaking. This article argues that the report is
      deeply conservative and unoriginal. It encourages medico-technical solutions to
      public health problems; it ignores macroeconomic determinants and other root
      causes of both poor health and poverty; it reverses public health logic and
      history; it is based on a set of flawed assumptions; it reflects one particular
      economic perspective to the exclusion of all others; and it recommends greater
      amounts of charity while preserving the status quo of a deeply unjust and
      irrational international economic order. A set of assumptions deriving from a
      neoliberal approach to health underlies the report. The author proposes an
      alternative set of assumptions deriving from a social justice and human rights
      based approach to health.

PMID- 15560434
TI  - Second thoughts on the flu vaccine.

PMID- 15560435
TI  - A crib-death gene?

PMID- 15560436
TI  - Model simulations for describing water transport in a landfill with bottom ash
      from a municipal solid waste incinerator (MSWI): model validation and scenarios.
AB  - In the present study the water movement in a bottom ash landfill from a municipal
      solid waste incinerator (MSWI) was investigated. The pore regime of such
      landfills consists of macropores (with diameter > 50 microm), which make up about
      two-thirds of the total porosity and micropores. The program MACRO, which
      describes flow through porous media and takes both macro- and micropore flows
      into account, was applied. The model was calibrated with a time series from the
      landfill Riet, near Winterthur in Switzerland. In the present study the model was
      recalibrated at a time series for 1 year. With this scenario the influence of an
      expected reduction or increase of the porosity on leachate behaviour of such
      landfills over a long time (> 100 years) was studied ('long-term behaviour'). It
      has been shown that reliable information about water percolation can only be
      provided by obtaining more information about the hydraulic structure of such
      landfills. In particular, the number of macropores and the porosity exert great
      influence on the water movement.

PMID- 15560437
TI  - Use of life cycle assessment as decision-support tool for water reuse and
      handling of residues at a Danish industrial laundry.
AB  - This analysis presents the results of a life cycle assessment (LCA) carried out
      on six alternative options for the recycling of water at a Danish industrial
      laundry for workwear. The study focuses on the handling and disposal of the wet
      residues generated when wastewater is treated for recycling, and in accounting
      for long-term potential toxicity impacts. The analysed options are a combination
      of two water-upgrading technologies: biofilter and ultrafiltration, and three
      residue disposal alternatives: biogas followed by incineration of sludge at local
      wastewater treatment plant, thermal vitrification treatment for production of
      vitrified sand, and mineralization in a sludge bed. It is concluded from the
      results that with the current Danish environmental policy priorities, the
      environmental impacts of highest priority are the toxicity effects derived from
      the presence of heavy metals in the residues. Heavy metals originate from the
      dirt in the workwear that is washed in the laundry. It is further concluded that
      the studied water treatment technologies satisfy both the need of clean water for
      recycling and simultaneously help controlling a safe disposal of pollutants by
      concentration of the residues. The results of the study also confirm the
      potential of LCA as a decision-support tool for assisting water recycling
      initiatives and for residue handling management. The handling of residues has
      been identified as a stage of the water recycling strategy that bears important
      environmental impacts. This holistic perspective provided by LCA can be used as
      input for the definition of environmental management strategies at an industrial
      laundry, and the prioritization of investments to the environmental profile of
      laundry processes. In this case-study, the results of the LCA are made
      operational by, for example, selecting the water treatment technology which is
      associated wih a safe disposal of the wet residue. It is important to bear in
      mind that such prioritization depends on national boundary conditions. In the
      case study analysed, the boundary conditions steer the weighing of the
      environmental impacts, following the current Danish environmental policy
      priorities.

PMID- 15560438
TI  - Exposure to bioaerosols and noise at a Finnish dry waste treatment plant.
AB  - Repeated measurements were carried out during two different campaigns between
      1998 and 2001 to assess the occupational hygiene at a Finnish dry waste treatment
      plant. The analytical determinations were done in four different places within
      the processing hall of the plant: near a conveyor belt, near a jigger screen,
      near an after-crusher and near a bailer. Measurements were also carried out in a
      coffee room for employees. Concentrations of bacteria, fungi and actinomycetes
      were determined by two methods (six-stage impactor and Camnea method) and levels
      of endotoxins, dust and noise were also investigated. High concentrations of
      microbes and endotoxins and the noise level were found to be a real problem in
      the waste processing hall. Microbe concentrations were highest during management
      of the dry waste fraction. Endotoxin concentrations all exceeded the threshold
      value of 200 EU m(-3) irrespective of the measurement place, with the only
      exception near the after-crusher where the average concentration was always as
      low as 60 EU m(-3). The noise level exceeded the Finnish threshold value of 85
      dBA. Problems were not easily solved through technical modifications and more
      radical improvements are needed. Improvements in reliability are also required in
      the measuring methods before their application in waste treatment plants. In
      particular, a new method of dust collection is recommended.

PMID- 15560439
TI  - Use of mix of clay/solid waste from steel works for civil construction materials.
AB  - The present study focuses on the use of solid waste generated by the steel works
      in Brazil for manufacturing clay-based structural products. The waste sample was
      characterized regarding chemical composition, X-ray diffraction, particle size,
      morphology, specific surface and plastic properties. The waste was added in
      gradual proportions to a kaolinitic clay from zero up to 3 wt.%. Ceramic bodies
      were formed by vacuum extrusion and fired at 950 degrees C. The physical
      mechanical properties (linear shrinkage, water absorption, apparent density and
      flexural strength) of the resulting clay/solid waste mixtures were determined. In
      addition, leaching tests were performed according Brazilian Standards as well as
      a preliminary analysis of gases evolved during the thermal process. It was found
      that the solid waste is formed by irregular particles, ranging in size from 1 to
      500 microm. The test results indicate that solid wastes generated by steel works
      can be used as filler in construction materials, thereby increasing reuse in an
      environmentally safe manner.

PMID- 15560440
TI  - Determination of the initial exothermic reaction of shredded tyres with wire
      content.
AB  - This paper presents the cause of exothermic reactions in shredded tyre with
      exposed wire content in shredded tyre piles. Data indicate that the oxidation of
      exposed steel wires is the exothermic reaction in shredded tyre embankments. This
      would lead to spontaneous combustion. Reaction of the steel with the sulphur or
      the carbon black appears not to be the source of the exothermic. Laboratory tests
      have been conducted to determine the heat transfer properties of the materials
      that compose tyres (i.e., tyre rubber and wires) by using a hot-plate apparatus.
      In addition, one-dimensional heat conduction experiments were conducted to
      compare the flow of heat through the materials while varying the physical and
      environmental conditions. The physical conditions were the size of tyre shred,
      water content, and wire contents. An exothermic reaction occurred when exposed
      wire was present but not when it was absent. A one-dimensional heat transfer
      equation was developed, and parametric studies were conducted to verify the
      laboratory model. Exothermic reaction was found to increase linearly with
      temperature, size and shape of the shredded tyres, density, amount of wire in
      shredded tyres, and water content.

PMID- 15560441
TI  - Removal of ammoniacal nitrogen (N-NH3) from municipal solid waste leachate by
      using activated carbon and limestone.
AB  - The presence of ammoniacal nitrogen (N-NH3) in leachate is one of the problems
      normally faced by landfill operators. Slow leaching of wastes producing nitrogen
      and no significant mechanism for transformation of N-NH3 in the landfills causes
      a high concentration of ammoniacal nitrogen in leachate over a long period of
      time. A literature review showed that the removal of ammoniacal nitrogen from
      leachate was not well documented and to date, there were limited studies in
      Malaysia on this aspect, especially in adsorption treatment. The main objective
      of the present study was to investigate the suitability of activated carbon,
      limestone and a mixture of both materials as a filtering medium, in combination
      with other treatments capable of attenuating ammoniacal nitrogen which is present
      in significant quantity (between 429 and 1909 mg L(-1)) in one of the landfill
      sites in Malaysia. The results of the study show that about 40% of ammoniacal
      nitrogen with concentration of more than 1000 mg L(-1) could be removed either by
      activated carbon or a mixture of carbon with limestone at mixture ratio of 5:35.
      This result shows that limestone is potentially useful as a cost-effective medium
      to replace activated carbon for ammoniacal nitrogen removal at a considerably
      lower cost.

PMID- 15560442
TI  - Processing of copper converter slag for metals reclamation: Part II:
      mineralogical study.
AB  - Chemical and mineralogical characterizations of a copper converter slag, and its
      products obtained by curing with strong sulphuric acid and leaching with hot
      water, were carried out using ore microscopy, scanning electronic microscopy with
      energy dispersive spectrometry, wave-length dispersive X-ray fluorescence
      spectrometry, X-ray diffractometry and chemical phase analysis, which provided
      necessary information to develop a new process for treating such slag and further
      understanding of the chemical and mineralogical changes in the process.

PMID- 15560443
TI  - Foamed lightweight materials made from mixed scrap metal waste powder and sewage
      sludge ash.
AB  - The porous properties and pozzolanic effects of sewage sludge ash (SSA) make it
      possible to produce lightweight materials. This study explored the effects of
      different metallic foaming agents, made from waste aluminium products, on the
      foaming behaviours and engineering characteristics, as well as the microstructure
      of sewage sludge ash foamed lightweight materials. The results indicated that
      aluminium powder and mixed scrap metal waste powder possessed similar chemical
      compositions. After proper pre-treatment, waste aluminium products proved to be
      ideal substitutes for metallic foaming agents. Increasing the amount of mixed
      scrap metal waste by 10-15% compared with aluminium powder would produce a
      similar foaming ratio and compressive strength. The reaction of the metallic
      foaming agents mainly produced pores larger than 10 microm, different from the
      hydration reaction of cement that produced pores smaller than 1 microm mostly. To
      meet the requirements of the lightweight materials characteristics and the
      compressive strength, the amount of SSA could be up to 60-80% of the total
      solids. An adequate amount of aluminium powder is 0.5-0.9% of the total solids.
      Increasing the fineness of the mixed scrap metal waste powder could effectively
      reduce the amount required and improve the foaming ratio.

PMID- 15560444
TI  - Integrated geophysical surveys on waste dumps: evaluation of physical parameters
      to characterize an urban waste dump (four case studies in Italy).
AB  - Geophysical surveys were carried out on different waste dumps to evaluate key
      geometric and physical parameters. Depending on the dump dimensions and physical
      characteristics different geophysical techniques were used. Vertical electrical
      sounding, electrical resistivity tomography, induced polarization and seismic
      refraction techniques were integrated to eliminate the non-uniqueness of
      solutions and for a better understanding of the results. Physical parameters
      inside and outside the dumps were compared. The change of physical parameters
      such as resistivity, chargeability, and P-wave velocity allowed evaluation of
      waste dump geometry, leachate saturation levels, and thickness of waste.
      Furthermore, in illegal dumps, the size and waste type disposed could be
      evaluated. Calculated results were compared with plans and book-keeping from the
      dumps investigated.

PMID- 15560445
TI  - Medical waste management in Trachea region of Turkey: suggested remedial action.
AB  - The main objective of this paper was to analyse the present status of medical
      waste management in the Trachea region of Turkey and subsequently to draw up a
      policy regarded with generation, collection, on-site handling, storage,
      processing, recycling, transportation and safe disposal of medical wastes. This
      paper also presents the results of study about awareness on how to handle expired
      drugs. Initially all health-care establishments in Tekirdag, Edirne and
      Kyrklareli provinces in Trachea region were identified and the amounts of
      hospital wastes generated by each of them were determined. Current medical waste
      management practices, including storage, collection, transportation and disposal,
      in surveyed establishments were identified. Finally, according to results,
      remedial measurements for medical waste management in these establishments were
      suggested. Unfortunately, medical wastes are not given proper attention and these
      wastes are disposed of together with municipal and industrial solid wastes. The
      current disposal method is both a public health and environmental hazard. When
      landfill sites are visited, many scavengers can be seen sorting for recyclable
      materials, a practice which is dangerous for the scavengers. In addition, it was
      found that some staff in health-care establishments are unaware of the hazard of
      medical wastes. It is concluded that a new management system, which consists of
      segregation, material substitution, minimization, sanitary landfilling and
      alternative medical waste treatment methods should be carried out. For the best
      appropriate medical waste management system, health-care establishment employers,
      managers and especially the members of house- keeping divisions should be
      involved in medical waste management practice.

PMID- 15560446
TI  - [Treatment of menorrhagia: drugs or surgery?].

PMID- 15560447
TI  - [Epidemiology of osteoporosis in Finland].

PMID- 15560448
TI  - [Obesity and sleeping disorders].

PMID- 15560449
TI  - [Expected life span, aging population and health problems in Finland and
      elsewhere].

PMID- 15560450
TI  - [Childhood chronic diseases and bone development].

PMID- 15560451
TI  - [Epidemiology, diagnosis and surgical treatment of gastrointestinal carcinoids].

PMID- 15560452
TI  - [Pinch grafting in treatment of leg ulcers].

PMID- 15560453
TI  - [Speech development disorders in children].

PMID- 15560454
TI  - [Food allergies among children].

PMID- 15560455
TI  - [Smoking and attempted suicide among adolescent psychiatric patients].

PMID- 15560456
TI  - [Erectile dysfunction].

PMID- 15560457
TI  - [Otto Makila:Omega I].

PMID- 15560458
TI  - [Tuberculosis as a global problem].

PMID- 15560459
TI  - [What does the genome sequence of tuberculosis bacteria reveal to us?].

PMID- 15560460
TI  - [Modern diagnostics of Mycobacterium tuberculosis].

PMID- 15560461
TI  - [Disease spectrum caused by atypical mycobacteria].

PMID- 15560462
TI  - [Lymphadenitis in the left groin due to Bacillus Calmette-Guerin (BCG)
      vaccination].

PMID- 15560463
TI  - [Central nervous system tuberculosis in children].

PMID- 15560464
TI  - [New form of old disease, tuberculous peritonitis].

PMID- 15560465
TI  - [200 years Carl Freiherr von Rokitansky].

PMID- 15560466
TI  - [Rokitansky and the Vienna Medical School--from the philosophy of nature to
      natural science].
AB  - On February 19th 2004 we celebrated the 200th anniversary of Carl Rokitansky's
      birth. Together with Morgagni and Virchow, Rokitansky paved the way for the
      development of modern pathology. In addition, he was the co-founder of the so
      called Second Vienna Medical School. Rokitansky represents a personality on the
      threshold of the change in medicine from a phenomenological-dominated philosophy
      to an evidence-based science. This jubilee essay aims at outlining this
      development particularly with regard to the Vienna Medical School before and
      after Rokitansky.

PMID- 15560467
TI  - [A life on the threshold].

PMID- 15560468
TI  - [Rokitansky and Virchow--the giants of pathology in disputatio].
AB  - On the occasion of the bicentenary of Carl Rokitanskys birth, I was kindly asked
      to review the relationship between the two great pathologists, Rokitansky and
      Virchow. As Virchow specialist and editor of the first complete edition of his
      work, I found the task of writing about their relationship particularly
      interesting. Although much has written on the subject, I tried to find new points
      to further illuminate their relationship.

PMID- 15560469
TI  - ["Indagandis sedibus et causis morborum"--development of pathophysiology as
      Rokitansky's desiderate].

PMID- 15560470
TI  - [Rokitansky's first description of a spondylocostal dysplasia, dysostosis].
AB  - The bicentenary of Carl Rokitansky's birth prompted us to evaluate his less well
      known work related to osteopathology. Of various articles containing
      humoropathological interpretations of osseous diseases, one work should be
      highlighted. It is, to the best of our knowledge, the first description of a
      spondylocostal dysplasia, re-discovered many years later, precisely described and
      accompanied by an excellent illustration.

PMID- 15560471
TI  - [Carl von Rokitansky: an exhibit on the occasion of his 200th birthday in the
      Vienna Society of Physicians].

PMID- 15560472
TI  - [Reflections of a present-day gynaecologist on the work of Carl Freiherr v.
      Rokitansky in the fields of pathology and anatomy].
AB  - With both its academic disciplines, gynaecology and obstetrics, the classical
      clinical subject of "gynaecology" in a wider sense was established mainly on the
      basis of a normal and, above all, abnormal, pathological morphology. It's a fact
      that the name of Carl Freiherr v. Rokitansky has always been remembered as an
      outstanding personality who established and dominated these fields of medical
      science. He described for the first time cases of endometriosis, strangulation of
      ovarian tumors, tuberculisation in the puerperal uterus, luteinic cysts in cases
      of hydatide moles, external wandering of the ovum, puerperal osteophytes and the
      spondylolisthetic pelvis. He created a linguistically and didactically suitable
      terminology: fibroids, later called fibromyomas, the kyphotic, the skoliotic and
      the coxalgic pelvis. Among the 14 medical terms used in pathological anatomy
      which are connected with the name of Rokitansky, two refer to the fields of
      gynaecology and obstetrics: the Mayer-v. Rokitansky-Kuster(-Hauser) syndrome in
      gynaecology and the Rokitansky spondylolisthetic pelvis in obstetrics.
      Rokitansky's authoritarian way of advocating the theory of Ignaz Philipp
      Semmelweis concerning the aetiology of puerperal fever plays an important part in
      both biographies. The 200th birthday of the founder of modern pathological
      anatomy is reason enough to look at Rokitansky's work from the point of view of
      the present-day gynaecologist.

PMID- 15560473
TI  - [The role of alcohol and/or benzodiazepines in occupational accidents compared to
      accidents due to other causes].
AB  - All patients who were admitted within one year to the Department of Traumatology
      of the Innsbruck University Hospital as a result of an accident were included in
      this epidemiological study: a total of 1611 patients. 18.9% (n = 304) of these
      patients were injured as a result of a work-related accident and the remaining
      81.2% (n = 1307) were involved in accidents due to other causes. Within the group
      of patients involved in work-related accidents, alcohol consumption was more
      frequent in males (13.3%) than in females (1.8%) (p = 0.016) and clearly lower
      than in patients injured by accidents due to other causes. In work--related
      accidents we found a correlation between the educational standard of patients and
      the frequency of alcohol consumption. The mean blood alcohol concentration was
      lower in patients involved in work-related accidents (0.76 +/- 0.58 g/l) compared
      to other injuries (1.63 g/l +/- 0.74 g/l). No correlations were found concerning
      benzodiazepine use and demographic variables and all measured benzodiazepine
      plasma levels were within the therapeutic range.

PMID- 15560474
TI  - Construction and application of a stoichiometric displacement model for retention
      in chiral recognition of molecular imprinting.
AB  - To do an extensive investigation of the chiral recognition mechanism of the
      molecular imprinting technique, two kinds of enantio-selective molecularly
      imprinted polymers (MIPs), N-tert-butoxycarbonyl-L-tryptophan (N-Boc-L-Trp) and N
      tert-butoxycarbonyl-L-tyramine (N-Boc-L-Tyr), were synthesized by photo-induced
      and thermal-induced polymerization, respectively, and were employed as the
      stationary phase in liquid chromatography. A stoichiometric displacement model
      for retention (SDM-R) was successfully constructed and applied to evaluate the
      chiral separation of the MIPs. The simulation results showed that the values of
      ln k' in the proposed SDM-R could be employed to characterize the efficiency of
      the MIP's total separation, and the value of n could be used to denote the space
      effect of the enantiomers interacting with the MIPs when the interaction between
      the solutes and MIPs was a hydrogen-bonding interaction. Further studies showed
      that the suitability of the MIP cavity structure mainly determined the chiral
      recognition ability of the imprinting system, when a strong hydrogen-bond
      competitive solvent was added into the mobile phase.

PMID- 15560475
TI  - Multivariate adaptive regression splines (MARS) in chromatographic quantitative
      structure-retention relationship studies.
AB  - The multivariate adaptive regression splines (MARS) methodology was applied to
      build quantitative structure-retention relationships (QSRRs). The response
      (dependent variable) in the MARS models consisted of the logarithms of the
      extrapolated retention factors (log k(w)) of 83 structurally diverse drugs on a
      Unisphere PBD column, using isocratic elutions at pH 11.7. A set of 266 molecular
      descriptors was used as predictor (independent) variables in the MARS model
      building. The optimal MARS model uses 34 basis functions to describe the
      retention and has acceptable predictive properties for new objects. The molecular
      descriptors included in the model describe hydrophobicity, molecular size,
      complexity, shape and polarisability. Some additional MARS models were created
      using alternative strategies. These include models with log P as the single
      predictor and models obtained with only the three most important molecular
      descriptors. The use of classification and regression trees (CART) as feature
      selection technique for predictor variables used in the MARS model was also
      investigated. Further, it is also studied whether allowing quadratic terms
      instead of interaction terms might lead to better MARS models.

PMID- 15560476
TI  - High-performance liquid chromatography of di- and trisubstituted aromatic
      positional isomers on 1,3-alternate 25,27-dipropoxy-26,28-bis-[3-propyloxy]
      calix[4]arene-bonded silica gel stationary phase.
AB  - A new 1,3-alternate 25,27-dipropoxy-26,28-bis-[3-propyloxy]-calix[4]arene-bonded
      silica gel stationary phase (1,3-Alt CalixPr) has been prepared and used for the
      separation of di- and trisubstituted aromatic positional isomers by HPLC. The
      effect of organic modifier content, pH and column temperature on retention and
      selectivity of the benzene derivatives were studied. The retention mechanism was
      also discussed. The results indicated that the stationary phase behaves like a
      reversed-phase packing. However inclusion, hydrophobic, hydrogen bonding and pi
      pi interactions seem to be involved in separation process.

PMID- 15560477
TI  - Model-based optimization of a preparative ion-exchange step for antibody
      purification.
AB  - A method using a model-based approach to design and optimize an ion-exchange step
      in a protein purification process is proposed for the separation of IgG from a
      mixture containing IgG, BSA and myoglobin. The method consists of three steps. In
      the first step, the model is calibrated against carefully designed experiments.
      The chromatographic model describes the convective and dispersive flow in the
      column, the diffusion in the adsorbent particles, and the protein adsorption
      using Langmuir kinetics with mobile phase modulators (MPM). In the second step,
      the model is validated against a validation experiment and analyzed. In the third
      and final step, the operating conditions are optimized. In the optimization step,
      the loading volume and the elution gradient are optimized with regard to the most
      important costs: the fixed costs and the feed cost. The optimization is achieved
      by maximizing the objective functions productivity (i.e. the production rate for
      a given amount of stationary phase) and product yield (i.e. the fraction of IgG
      recovered in the product stream). All optimization is conducted under the
      constraint of 99% purity of the IgG. The model calibration and the analysis show
      that this purification step is determined mainly by the kinetics, although as
      large a protein as IgG is used in the study. The two different optima resulting
      from this study are a productivity of 2.7 g IgG/(s m3) stationary phase and a
      yield of 90%. This model-based approach also gives information of the robustness
      of the chosen operating conditions. It is shown that the bead diameter could only
      be increased from 15 microm to 35 microm with maximum productivity and a 99%
      purity constraint due to increased diffusion hindrance in larger beads.

PMID- 15560478
TI  - The effects of aromatic substituents on the chromatographic enantioseparation of
      diarylmethyl esters with the whelk-O1 chiral stationary phase.
AB  - Members of a series of diarylmethanols, diarylmethyl pivalates, and diarylmethyl
      acetates (analyte sets 1-26) were enantioresolved with the (S,S)-Whelk-O1 chiral
      stationary phase (CSP). An analogue of the (S,S)-Whelk-O1 selector was combined
      with enantioenriched samples of the various diarylmethyl pivalates and thereby
      used as a chiral solvating agent (CSA) for high field 1H NMR studies. The
      absolute configurations of a number of chiral diarylmethyl pivalates were
      assigned using this approach, and hydrolysis of the pivalates allowed assignment
      of the absolute configurations of the corresponding diarylmethanols.
      Chromatographic, 1H NMR, and X-ray evidence are given in support of a chiral
      recognition model for the enantioresolution of diarylmethyl esters on this CSP.

PMID- 15560479
TI  - Highly sensitive and rapid normal-phase chiral screen using high-performance
      liquid chromatography-atmospheric pressure ionization tandem mass spectrometry
      (HPLC/MS).
AB  - In the last years, there has been an increasing demand on the development of
      quantitative assays for determination of enantiopurity. Herein, we present a
      methodology based on a direct linking of an atmospheric pressure ionization mass
      spectrometer (MS-APCI) with a high-performance liquid chromatography HPLC (DAD)
      system, operated under normal-phase mode and without post-column addition of MS
      compatible solvents, which provides the high specificity/selectivity
      (identification of isomers in complex mixtures) and accuracy (1-2% area level)
      required for daily chiral studies. As result of the success of our screen, the
      preparation of individual enantiomers or the racemic mixture in our Drug
      Discovery Research Laboratories at Lilly, Spain is usually not required.
      Therefore, additional non-valuable synthetic work is eliminated.

PMID- 15560480
TI  - Supported liquid membrane microextraction with high-performance liquid
      chromatography-UV detection for monitoring trace haloacetic acids in water.
AB  - Supported liquid membrane microextraction (SLMME) with high-performance liquid
      chromatography (HPLC)-UV detection has been developed for the extraction,
      preconcentration, and determination of all the nine haloacetic acids (HAAs) in
      water. The HAAs are extracted into a supported liquid membrane, and then back
      extracted into few microliters of an acceptor solution. The extract was directly
      analyzed by HPLC-UV with a 15-min run. Enrichment factors in the range of 300
      3000 were obtained in a 60-min extraction, and detection limits were at low to
      sub-microg/L level with R.S.D. values between 1.5 and 10.8%. The parameters that
      affected analyte enrichment were studied. This approach offers an attractive
      alternative to the current US Environmental Protection Agency standard methods
      for HAA analysis, which require complex sample preparation and derivatization
      prior to analysis by gas chromatography. SLMME can also be used in conjunction
      with other analytical schemes, such as, ion chromatography and capillary
      electrophoresis.

PMID- 15560481
TI  - Preparative isolation and purification of coumarins from Cnidium monnieri (L.)
      Cusson by high-speed counter-current chromatography.
AB  - A high-speed counter-current chromatography (HSCCC) method for separation and
      purification of coumarins from Cnidium monnieri (L.) Cusson was developed by
      using stepwise elution with a pair of two-phase solvent system composed of light
      petroleum-ethyl acetate-methanol-water at volume ratios of 5:5:5:5, 5:5:6:4 and
      5:5:6.5:3.5. Five kinds of coumarins were obtained and yielded 7.6 mg of
      xanthotoxin(I), 7.6 mg of isopimpinellin(II), 9.7 mg of bergapten(III), 60.5 mg
      of imperatorin(IV), 50.6 mg of osthole(V) and 10.2 mg of one unknown compound
      from 150mg crude sample. The purity of these compounds was 95.0%, 99.6%, 99.7%,
      100%, 100% and 98.1%, respectively, as determined by HPLC. Their structures were
      identified by 1H NMR.

PMID- 15560482
TI  - Determination of aliphatic amines in mineral flotation liquors and reagents by
      high-performance liquid chromatography after derivatization with 4-chloro-7
      nitrobenzofurazan.
AB  - The method described here fulfils the need for a suitable analytical method to
      determine the concentrations of single and mixed aliphatic amines in the range
      from hexylamine (C6) to octadecylamine (C18) in flotation test solutions and in
      commercial flotation collectors. Amines do not have a UV-vis spectrum in aqueous
      solution but by reacting an amine-containing solution with 4-chloro-7
      nitrobenzofurazan solution (chloro-NBD), derivatized products (amino-NBDs) are
      formed which have absorbance maxima at 470nm. Excess chloro-NBD and the amino
      NBDs can be separated from each other by high-performance liquid chromatography
      (HPLC) and their concentrations measured with a UV-vis detector. Important
      variables in the derivatization stage are pH, temperature, chloro-NBD
      concentration, and reaction time, all of which interact with each other. A three
      stage statistical procedure was used to determine the optimum conditions. In each
      stage, an 8-test design was used in which a high and low limit was set for each
      variable, and the chromatogram peak area of the derived amino-NBD was measured.
      The optimum derivatization conditions established were pH 8.9, chloro-NBD
      concentration 0.20% (w/v), temperature 70 degrees C, and reaction time 60 min.
      Optimum elution conditions for chromatography were an eluent containing 80% (v/v)
      acetonitrile in aqueous solution containing 40mM acetic acid at pH 4.5. With a
      flow rate of 2.0 ml/min, dodecylamine had a retention time of about 3 min,
      whereas octadecylamine had a retention time of 44 min. Straight-line calibration
      curves were obtained up to at least 200 ppm of amine in solution. The lower limit
      of detection was estimated to be 0.05 microM (10ppb) with a signal to noise ratio
      of 3. No interfering substances were found. The method was successfully applied
      to the analysis of solutions from an actual flotation test and to a solid
      commercial amine.

PMID- 15560483
TI  - Mass spectrometric characterization of peptides derived by peptic cleavage of
      bovine beta-casein.
AB  - This study investigated the digestion of the milk protein beta-casein with pepsin
      under gastro-analogous conditions. Peptide sequences were identified using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry with post
      source decay as well as liquid chromatography-tandem mass spectrometry by means
      of database searching. The new software tool, Mascot Distiller, improved the
      identification rate remarkably. In the case of small peptides, such as di- and
      tri-peptides, which are promising candidates for intestinal absorption and
      possible biological effects, identification was possible only after spectrum
      simulation and manual matching. A list of 41 identified peptides having 2-36
      amino acids is given, and unexpected cleavage sites for pepsin are reported.
      Sequence coverage was 75%.

PMID- 15560484
TI  - Selective and mild adsorption of large proteins on lowly activated immobilized
      metal ion affinity chromatography matrices. Purification of multimeric
      thermophilic enzymes overexpressed in Escherichia coli.
AB  - A strategy to selectively adsorb large proteins on immobilized metal ion affinity
      chromatography supports is presented. It is based on the fact that large proteins
      have a large surface that permits the long distance interaction with groups
      placed quite far apart (very dispersed onto the support surface) in the support,
      therefore, even using lowly activated supports, these proteins may be able to
      yield multiple interactions with the support, which is not possible for smaller
      proteins. This has been shown using a crude extract from Escherichia coli, where
      only large proteins were adsorbed on supports having 0.25 micromol of metallic
      groups/g of support. Then, these lowly activated supports have been used for
      purifying multimeric enzymes from thermophilic organisms (alpha- and beta
      galactosidases from Thermus sp. strain T2) cloned and over-expressed in
      mesophilic ones. A previous heating step of the crude extract destroyed the
      quaternary structure of all multimeric enzymes from the host (E. coli). Thus, the
      only large protein remaining in the supernatant of this heated extract are the
      cloned multimeric thermophilic enzymes, permitting their very simple purification
      by using only one chromatographic step.

PMID- 15560485
TI  - Mass spectrometric determination of acromelic acid A from a new poisonous
      mushroom: Clitocybe amoenolens.
AB  - As Clitocybe acromelalga, the mushroom Clitocybe amoenolens is responsible for
      erythermalgia. Acromelic acids isolated from C. acromelalga have been suspected
      to be to some extend the active principles. The objective was to develop a
      specific and sensitive liquid chromatographic-mass spectrometric method that
      would allow acromelic acid A identification and quantification in mushrooms. The
      method involved a single-step methanol-water extraction followed by a selective
      cleanup of the extract with solid-phase extraction cartridges (strong-anion
      exchange). The chromatographic separation was achieved on a porous graphitic
      carbon column with acetonitrile-water-formic acid as mobile phase. Detection was
      done with a mass analyzer equipped with a TurboIonSpray source, operated in the
      negative ionization mode. Acromelic acid A concentration was determined in dried
      mushroom at around 325 ng/mg in C. amoenolens and 283 ng/mg in C. acromelalga.

PMID- 15560486
TI  - Determination of tetracyclines in ovine milk by high-performance liquid
      chromatography with a coulometric electrode array system.
AB  - A method has been developed to analyze residual tetracyclines (TCs)
      (oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC), methacycline
      (MTC), doxycycline (DC)) in ovine milk, using high-performance liquid
      chromatography (HPLC) with a coulometric electrode array system. The samples were
      pretreated, using liquid-liquid extraction based on hexane. The chromatography
      was performed, using a C18 column (150 mm x 4 mm i.d. and 5 microm) with a mobile
      phase: sodium phosphate monobasic dihydrate (pH 2.2, 0.05 M)-acetonitrile (78:22,
      v/v). The flow rate of mobile phase was kept constantly at 1ml/min. The residues
      were monitored by an ESA electrochemical detector. Potentials of four electrodes
      in series were set at 400, 660, 680 and 700 mV, respectively. The first electrode
      was set to remove those interfering substances that may co-elute with TCs and the
      other three electrodes were used for quantification. The maximal potential of our
      detection was 700 mV. Calibration curve showed good linearity and the detection
      limit of TCs was 12.5, 20, 25, 10 and 25 ng/ml, respectively. Optimization of the
      pH of the mobile phase, the proportion of acetonitrile and the pH of the
      pretreatment were also performed. Recoveries of TCs from spiked samples were more
      than 88% and the relative standard deviations were less than 4.3%. This method
      was reliable, sensitive, economical and suited for routine monitoring of TC
      residues in ovine dairy milk.

PMID- 15560487
TI  - Determination of solid products from the de-polymerization of poly(trimethylene
      terephthalate) in supercritical methanol.
AB  - A method based on high-resolution size-exclusion chromatography (SEC) was
      established to analyze the solid products from the depolymerization of
      poly(trimethylene terephthalate) (PTT) in supercritical methanol. In the
      qualitative analysis, four factors (chromatographic retention time, qualitative
      multi-wavelength ultraviolet spectra, linear internal-insert SEC and qualitative
      IR spectra) were considered. The main solid products from the process were
      dimethyl terephthalate (DMT), methyl-(2-hydroxypropyl) terephthalate (MHPT),
      bis(2-hydroxypropyl) terephthalate (BHPT), methyl-(2-hydroxyethyl) terephthalate
      (MHET), bis(2-hydroxyethyl) terephthalate (BHET), and hydroxyethyl-(2
      hydroxypropyl) terephthalate (HEHPT). It is found that the method is of a high
      resolution among the solid products and has a fine repeatability. In addition,
      the solid products from the de-polymerization of poly(ethylene terephthalate)
      (PET) in similar process were also analyzed by this method. Furthermore, the
      effects of supercritical conditions on the distribution of the products were also
      discussed.

PMID- 15560488
TI  - Separation and characterization of functional poly(n-butyl acrylate) by critical
      liquid chromatography.
AB  - The separation of functional poly(n-butyl acrylate) (PnBA) polymers based on the
      number of end-groups under critical liquid chromatography (LC) conditions has
      been studied using a bare-silica column. The (near-) critical solvent
      compositions for non-, mono-, and difunctional (telechelic) carboxyl-PnBAs were
      determined in normal-phase LC, using mixtures of acetonitrile, acetic (or formic)
      acid, and dichloromethane of varying composition. Some formic or acetic acid had
      to be added to the mobile phase to elute PnBA polymers with carboxyl end-groups.
      The critical solvent compositions obtained were not exactly the same for non-,
      mono-, and difunctional PnBA polymers. These were unusual experimental
      observation, but they were in agreement with theoretic predictions. Nevertheless,
      low-molecular-mass PnBA samples were successfully separated according to the
      carboxyl functionality at (near-) critical conditions. With the aid of mass
      spectrometry (MS), the (near-) critical separation of low-molecular-mass PnBA
      polymers was confirmed to be mainly based on the carboxyl functionality.
      Calibration curves for evaporative light-scattering detection (ELSD) were used
      for quantitative analysis of carboxyl-functional PnBA polymers. The results
      proved that nearly ideal functionalities (average number of carboxyl end-groups
      per molecule up to 1.99) were achieved for telechelic PnBAs prepared by one-step
      reversible addition-fragmentation chain-transfer (RAFT) polymerization of PnBA.

PMID- 15560489
TI  - An efficient new method for extraction, separation and purification of psoralen
      and isopsoralen from Fructus Psoraleae by supercritical fluid extraction and high
      speed counter-current chromatography.
AB  - Psoralen and isopsoralen were extracted from Fructus Psoraleae (Psoralea
      corylitolia L.) by supercritical CO2. The effect of various parameters, i.e.,
      pressure, temperature and sample particle size on yield was investigated with an
      analytical-scale supercritical fluid extraction (SFE) system to find the optimal
      conditions. The process was then scaled up by 50 times with a preparative SFE
      system under the optimized conditions of pressure (26 MPa), temperature (60
      degrees C) and a sample particle size of 40-60 mesh. The yield of the preparative
      SFE was 9.1% and the combined yield of psoralen and isopsoralen was 2.5 mg/g of
      dry seeds. Psoralen and isopsoralen in the extract were separated and purified by
      high-speed counter-current chromatography with a two-phase solvent system
      composed of n-hexane-ethyl acetate-methanol-water (1:0.7:1:0.8, v/v), and the
      fractions were analyzed by HPLC, MS, 1HNMR and 13C NMR. The structures of the
      products were further confirmed by comparison with authentic samples (National
      Institute of the Control of Pharmaceutical and Biological Products, Beijing,
      China).

PMID- 15560490
TI  - Prediction of retention times and efficiency in linear gradient programmed
      pressure analysis on capillary columns.
AB  - A method for the prediction of the retention time and the resolution of
      chromatographic peaks in different experimental conditions by starting from few
      experimental data measured in isothermal and isobaric analyses was published
      previously. In this paper, the same mathematical model was implemented for
      calculating the retention times and the column efficiency in programmed pressure
      runs. Some models originated from the Golay equation and reported in the
      literature are compared, and a new modified equation for the calculation of the
      peak width at half height is proposed. The procedure for the prediction of the
      retention time and the peak width at half height at programmed pressure of the
      carrier gas and different column temperature and linear gradient by using
      retention data of different compounds obtained in few isobaric runs is described.
      The prediction of the retention time and the separation efficiency of compounds
      with different polarity gave good results for the programmed pressure runs with
      linear gradient. The effect of the variation of the initial parameters of the
      experimental analyses and of the mathematical model on the accuracy of the
      prediction has been evaluated.

PMID- 15560491
TI  - Prediction of retention times in linear gradient temperature and pressure
      programmed analysis on capillary columns.
AB  - The simultaneous temperature and inlet pressure programming (TPP) in gas
      chromatographic analysis decreases the retention time and the maximum value of
      temperature required for the elution of high boiling substances. Therefore,
      compounds sensitive to thermal degradation can be better analysed and column
      ageing is reduced. However, the empirical choice of proper analysis conditions
      requires many preliminary runs; this paper describes a procedure for the
      theoretical prediction of retention times in TPP using few preliminary runs
      carried out in isobaric and isothermal conditions. The used program permits the
      prediction of the retention times of the compounds analysed with any different
      TPP run carried out within the temperature and pressure ranges investigated with
      the preliminary runs. The influence of various analytical parameters on the
      accuracy of the prediction values was investigated. The proposed model also
      predicts the relative position in the chromatogram of closely eluting peaks and
      the possible coincidence of retention times or inversion of the elution order
      with changing temperature. It is also possible to foresee the analytical
      conditions, which offer a baseline separation of all of the peaks of the sample.

PMID- 15560492
TI  - Practical aspects of splitless injection of semivolatile compounds in fast gas
      chromatography.
AB  - Possibilities and practical aspects of implementation of splitless injection of
      larger volumes for fast GC purposes utilizing narrow-bore column, hydrogen as
      carrier gas, fast temperature programming under programmed flow conditions and
      commercial instrumentation were searched. As a model sample semivolatile
      compounds of a broad range of volatility and polarity (7 n-alkanes and 19
      pesticides) were chosen. Peak shapes, peak broadening and peak areas and its
      repeatability were evaluated under various experimental set-ups (liner/injection
      technique combinations). Various factors, such as liner design, injection
      technique, retention gap length, compound volatility and polarity, the solvent
      used, initial oven temperature influenced compound focusation and/or maximal
      injection volume. Combination of analytical column (CP-Sil 13 CB 25 m long, 0.15
      mm i.d., film thickness 0.4 microm) with normal-bore retention gap (1 m long,
      0.32 mm i.d.) allowed maximal injection volume 8 microl for 4 mm i.d. liner used
      without any peak distortion when solvent recondensation in the retention gap was
      employed.

PMID- 15560493
TI  - Gas chromatographic properties of common cholesterol and phytosterol oxidation
      products.
AB  - The most common cholesterol and phytosterol oxidation products found in
      foodstuffs or biological matrices are the 7alpha- and 7beta-hydroxysterol, 7
      ketosterol, 5alpha,6alpha- and 5beta,6beta-epoxysterol, and triol derivatives of
      sterols. This study focused on the preparation and purification of such products
      derived from campesterol, stigmasterol and beta-sitosterol. The identity of the
      substances was confirmed by mass spectroscopic analysis. The elution order of a
      complex mixture composed of the 7alpha- and 7beta-hydroxysterol, 7-ketosterol,
      5alpha,6alpha- and 5beta,6beta-epoxysterol, and triol derivatives of cholesterol,
      campesterol, stigmasterol and beta-sitosterol was recorded on an apolar as well
      as a medium-polarity capillary column in relation to two commonly used internal
      standards, i.e. alpha-cholestane and 19-hydroxy cholesterol. Flame-ionization
      detector as well as mass spectrometry response factors were derived from a
      gravimetrically prepared mixture of commercially available cholesterol oxide
      standards. It was proven that the ionization efficiency of cholesterol and
      phytosterol oxides are very similar and that response factors obtained for
      cholesterol oxidation products are also valid for quantitative work regarding
      phytosterol oxidation products.

PMID- 15560494
TI  - Comparison of extraction methods for quantitation of methionine and
      selenomethionine in yeast by species specific isotope dilution gas chromatography
      mass spectrometry.
AB  - Fourteen extraction methods commonly cited in the literature were evaluated for
      the quantitation of methionine (Met) and selenomethionine (SeMet) in a yeast
      candidate certified reference material (CRM). Species specific isotope dilution
      (ID) gas chromatography-mass spectrometry (GC-MS) was utilized to effectively
      compensate for potential errors, such as losses during derivatization and clean
      up steps. Despite different extraction methods, the same derivatization procedure
      using methyl chloroformate was applied with a single exception, which was based
      on digestion with cyanogen bromide with 2% SnCl2 in 0.1 M HCl. Significant
      differences in measured Met and SeMet concentrations were obtained when different
      extraction methods were used. A 4 M methanesulfonic acid reflux digestion was
      found to be the most efficient for both analytes. Digestion with CNBr with 2%
      SnCl2 in 0.1 M HCl for the determination of SeMet showed the second highest
      extraction efficiency. Despite frequent use of enzymatic hydrolysis for the
      extraction of SeMet from yeast, very low extraction efficiencies for both
      analytes were obtained for four of eight tested methods. Among these, the highest
      extraction efficiencies for both analytes were obtained using 20mg pronase and
      10mg lipase with incubation at 37 degrees C for 24 h. However, recoveries
      remained nearly 30 and 50% lower for Met and SeMet, respectively, compared to
      extraction with methanesulfonic acid. Lowest extraction efficiencies for both
      analytes were obtained when HCl or tetramethylammonium hydroxide (TMAH)
      digestions were used. Efficient extraction was also achieved using 200 mg (or 400
      mg) of protease XIV with incubation at 37 degrees C for 72 h (or 24 h).
      Concentrations of 3331+/-45 and 3334+/-39 microg g(-1) (mean and one standard
      deviation, n = 4) for SeMet were obtained using 200 mg (72 h incubation) and 400
      mg (24 h incubation) of protease XIV, respectively, in agreement with a value of
      3404+/-38 microg g(-1) obtained using a methanesulfonic acid reflux.

PMID- 15560495
TI  - Solid-phase extraction-gas chromatography-mass spectrometry using a fullerene
      sorbent for the determination of inorganic mercury(II), methylmercury(I) and
      ethylmercury(I) in surface waters at sub-ng/ml levels.
AB  - A novel, straightforward solid-phase extraction system for the determination of
      inorganic mercury and organomercury compounds in water is proposed. The analytes,
      in a buffer medium at pH 4.5, are sorbed as diethyldithiocarbamate complexes on a
      C60 fullerene column an subsequently eluted and derivatized with sodium tetra-n
      propylborate in ethyl acetate. Following elution, 1 microl of extract is injected
      into a gas chromatograph-mass spectrometer system. The proposed gas
      chromatography-mass spectrometry speciation method exhibits a linear range of 4-1
      ng/ml, and a detection limit of 1.5 ng/l (sample volume, 50 ml). Its
      repeatibility, as relative standard deviation (RSD) (from 11 standards containing
      50 ng/l for each analyte), is ca. 7%. No interferences from metals ions, such as
      Zn2+, Fe3+, Sb3+, As3+, Pb2+, Ni2+, Cu2+, Sn2+, Co2+, Mn2+ and Cd2+ were
      encountered at concentrations 1000 times higher than those of the mercury
      compounds. The method was used for the speciation of inorganic mercury,
      methylmercury and ethylmercury in various types of water including sea and waste
      water.

PMID- 15560496
TI  - Gel permeation chromatography followed by pyrolysis-gas chromatography-mass
      spectrometry via a solvent-evaporative interface.
AB  - The measurement of chemical composition as a function of molecular weight has
      always been a challenge for analytical chemists. In this paper, we present a
      unique way to combine gel permeation chromatography (GPC) with pyrolysis-gas
      chromatography-mass spectrometry (Py-GC-MS) for this purpose. A commercially
      available solvent-evaporative interface, originally designed for GPC-IR
      measurements, was used to deposit the eluent of GPC onto aluminum foil. Small
      strips of aluminum foil were cut and subjected to Py-GC-MS analysis. Compared
      with the GPC-IR measurements, the proposed technique offers the advantage of
      being able to distinguish between structurally similar monomers in a complex
      copolymer. As an example, a copolymer composed of four monomers was analyzed. The
      results clearly demonstrate that this technique can be applied to complex
      polymeric systems to yield information regarding chemical heterogeneity versus
      molecular weight.

PMID- 15560497
TI  - Speciation analysis of mercury by solid-phase microextraction and multicapillary
      gas chromatography hyphenated to inductively coupled plasma-time-of-flight-mass
      spectrometry.
AB  - This paper reports the development of an analytical approach for speciation
      analysis of mercury at ultra-trace levels on the basis of solid-phase
      microextraction and multicapillary gas chromatography hyphenated to inductively
      coupled plasma-time-of-flight mass spectrometry. Headspace solid-phase
      microextraction with a carboxen/polydimethylsyloxane fiber is used for
      extraction/preconcentration of mercury species after derivatization with sodium
      tetraethylborate and subsequent volatilization. Isothermal separation of
      methylmercury (MeHg), inorganic mercury (Hg2+) and propylmercury (PrHg) used as
      internal standard is achieved within a chromatographic run below 45 s without the
      introduction of spectral skew. Method detection limits (3 x standard deviation
      criteria) calculated for 10 successive injections of the analytical reagent blank
      are 0.027 pg g(-1) (as metal) for MeHg and 0.27 pg g(-1) for Hg2+. The
      repeatability (R.S.D., %) is 3.3% for MeHg and 3.8% for Hg2+ for 10 successive
      injections of a standard mixture of 10pg. The method accuracy for MeHg and total
      mercury is validated through the analysis of marine and estuarine sediment
      reference materials. A comparison of the sediment data with those obtained by a
      purge-and-trap injection (PTI) method is also addressed. The analytical procedure
      is illustrated with some results for the ultra-trace level analysis of ice from
      Antarctica for which the accuracy is assessed by spike recovery experiments.

PMID- 15560498
TI  - Analysis of conformational change of human serum albumin using chiral capillary
      electrophoresis.
AB  - The conformational change of human serum albumin (HSA) was studied through its
      binding with basic drug-mexiletine by chiral capillary electrophoresis. The
      effects of the conformational change of HSA resulted from pH, thermal, acute
      vibration, and alcohol on its chiral selectivity to mexiletine were investigated
      in detail. This study offers a simple and complementary method to investigate the
      binding of proteins with drugs and the characteristic of conformational change of
      protein. The method is easy to perform, high speed, low reagent consumption, and
      no modification is required to the commercially available CE instrument.

PMID- 15560499
TI  - Simultaneous determination of six main nucleosides and bases in natural and
      cultured Cordyceps by capillary electrophoresis.
AB  - A simple method is described for simultaneous determination of six main
      nucleosides and bases including adenine, uracil, adenosine, guanosine, uridine
      and inosine in Cordyceps by capillary electrophoresis (CE). Chemometric
      optimization based on central composite design was employed to find the optimum
      resolution. The optimum factor space was defined by three parameters: buffer
      concentration, pH and concentration of acetonitrile as organic modifier.
      Resolution (Rs) was employed to evaluate the response function. A running buffer
      composed of 500 mM boric acid, adjusted pH to 8.6 with sodium hydroxide and 12.2%
      acetonitrile as modifier was found to be the most appropriate for the separation.
      The contents of the six components were determined by using adenosine
      monophosphate as an internal standard. Furthermore, hierarchical clustering
      analysis based on characteristics of 32 peaks in CE profiles from the tested 12
      samples showed that natural and cultured Cordyceps were in different clusters.
      Adenosine and inosine were extracted as markers for discrimination of natural
      Cordyceps. The result of clustering based on the two peaks characteristics was in
      excellent agreement with that based on 32 peaks'. Thus, adenosine and inosine
      could be used as markers for quality control of natural and cultured Cordyceps.

PMID- 15560500
TI  - Short-capillary electrophoresis with electrochemiluminescence detection using
      porous etched joint for fast analysis of lidocaine and ofloxacin.
AB  - Fast analysis of ofloxacin and lidocaine, as bactericide and analgesic or
      anesthetics, is of clinic importance for understanding the patient's medical
      process. This paper presented a high throughput, simple analysis method of
      lidocaine and ofloxacin by capillary electrophoresis coupled with
      electrochemiluminescence (ECL) using porous etched joint. To shorten the analysis
      time and to improve the analytical performance, a capillary with 10 cm in length
      was used as the separation channel. The cyclic voltammograms of Ru(bpy)3(2+) with
      different capillary length at same field strength showed that the porous etched
      joint eliminated the effect of electrophoretic current on the ECL detection.
      Following micro total analysis systems (microTAS), some advantages of which this
      approach has, the fabrication of channel in chip was not needed. Compared with
      capillary electrophoresis with 40-cm-long capillary, the high sample throughput
      and low zone broadening may be the main advantage of the present system. Under
      optimal condition, the detection limits of lidocaine and ofloxacin based on peak
      height were 3.0 x 10(-8) and 5.0 x 10(-7) molL(-1) and a 60 h(-1) of sampling
      frequency was obtained. The precision (R.S.D.) of the migration time and the peak
      height for five replicate injections of a mixture of lidocaine (1.0 x 10(-6)
      molL(-1)) and ofloxacin (4.0 x 10(-6) molL(-1)) were 3.2-3.9% and 4.7-5.3%,
      respectively.

PMID- 15560501
TI  - Further research on iodine speciation in seawater by capillary zone
      electrophoresis with isotachophoresis preconcentration.
AB  - A novel, simple and highly sensitive CE method was developed to determine total
      iodine (TI) in seawater. The method is based on the on-capillary reduction of
      iodine species to iodide by a reductant, introduced into the capillary before
      sample injection, the preconcentration of iodide using isotachophoresis, followed
      by its UV detection. Under optimized conditions for reduction and CE separation,
      the limit of detection for TI (S/N = 3) reached 0.4 microg L(-1) (226 nm). The
      repeatability of migration time and peak area, expressed by relative standard
      deviation, was 0.46 and 1.45%, respectively (n = 19). The correlation factor was
      0.9991 (n = 10) for the concentration range of 12-115 microg I L(-1). The CE
      results obtained for the real seawater analysis agreed with the data of ion
      chromatography. To determine the genuine TI by the proposed method, organic
      iodinated compounds in the sample were treated with H202 and irradiation with UV
      light before analysis.

PMID- 15560502
TI  - High-performance liquid chromatographic determination of alpha-aminonitrile
      enantiomers after derivatization with o-phthalaldehyde and chiral thiols.
AB  - o-Phthalaldehyde in combination with chiral thiols is described as a chiral
      reagent for the resolution of the enantiomers of alpha-H-alpha-aminonitriles and
      alpha-alkyl-alpha-aminonitriles. Separation of the resulting diastereomers was
      carried out by reversed-phase chromatography and the derivatives were detected at
      UV 340 nm. The identity of the diastereomeric derivatives was confirmed by LC-MS.
      Among the chiral thiols tested, N-acetyl-D-penicillamine and beta
      mercaptoisobutyric acid gave the best resolution for the alpha-aminonitriles
      studied. For quantitative enantiomeric excess determination, beta
      mercaptoisobutyric acid was chosen as this thiol could be obtained in high
      enantiomeric purity from a commercial source. The rate of the reaction of various
      alpha-aminonitriles with o-phthalaldehyde and beta-mercaptoisobutyric acid was
      studied. The accuracy of the method was investigated by a comparison of
      theoretical and measured enantiomeric excess.

PMID- 15560503
TI  - On-line sample cleanup and chiral separation of gemifloxacin in a urinary
      solution using chiral crown ether as a chiral selector in microchip
      electrophoresis.
AB  - In chiral capillary electrophoresis of primary amine enantiomers using (+)-18
      crown-6-tetracarboxylic acid (18C6H4) as a chiral selector, the presence of
      alkaline metal ions in the sample solution as well as in the run buffer is
      undesirable due to their strong competitive binding with 18C6H4. A channel
      coupled microchip electrophoresis device was designed to clean up alkaline metal
      ions from a sample matrix for the chiral analysis of amine. In the first channel,
      the metal ions in the sample were monitored by indirect detection using quinine
      as a chromophore and drained to the waste. In the second separation channel,
      gemifloxacin enantiomers, free of the alkaline metal ions, were successfully
      separated using only a small amount of the chiral selector (50 microM 18C6H4).

PMID- 15560504
TI  - Development of an extraction method for the determination of zearalenone in corn
      using less organic solvents.
AB  - A method for the determination of zearalenone in corn has been developed applying
      pressurised liquid extraction (PLE) and using environmentally acceptable and less
      noxious organic solvents. The extracted samples were analysed with liquid
      chromatography coupled to mass spectrometry (LC-MS) equipped with an electrospray
      (ESI) ionisation interface. The optimised extraction mixture was isopropanol and
      an aqueous solution of triethylamine (1%) 50:50 (v/v), which allowed to halve the
      use of organic solvent compared to the method proposed by ISO. When applying the
      optimised method to five different naturally contaminated corn samples the
      obtained concentrations were slightly increased compared to the analysis using
      the previously used extraction solvent (acetonitrile-methanol). The relative
      standard deviation (RSD, n = 3) varied between 4 and 10% depending on the
      concentration level of the target analyte in the test material.

PMID- 15560505
TI  - Toying with science.

PMID- 15560506
TI  - A comparison of auditory and visual apparent motion presented individually and
      with crossmodal moving distractors.
AB  - Unimodal auditory and visual apparent motion (AM) and bimodal audiovisual AM were
      investigated to determine the effects of crossmodal integration on motion
      perception and direction-of-motion discrimination in each modality. To determine
      the optimal stimulus onset asynchrony (SOA) ranges for motion perception and
      direction discrimination, we initially measured unimodal visual and auditory AMs
      using one of four durations (50, 100, 200, or 400 ms) and ten SOAs (40-450 ms).
      In the bimodal conditions, auditory and visual AM were measured in the presence
      of temporally synchronous, spatially displaced distractors that were either
      congruent (moving in the same direction) or conflicting (moving in the opposite
      direction) with respect to target motion. Participants reported whether
      continuous motion was perceived and its direction. With unimodal auditory and
      visual AM, motion perception was affected differently by stimulus duration and
      SOA in the two modalities, while the opposite was observed for direction of
      motion. In the bimodal audiovisual AM condition, discriminating the direction of
      motion was affected only in the case of an auditory target. The perceived
      direction of auditory but not visual AM was reduced to chance levels when the
      crossmodal distractor direction was conflicting. Conversely, motion perception
      was unaffected by the distractor direction and, in some cases, the mere presence
      of a distractor facilitated movement perception.

PMID- 15560507
TI  - Simultaneity constancy.
AB  - Sound and light take different amounts of time to reach their respective
      receptors, to be transduced, and to be transmitted to the cortex. Their
      processing times also vary with factors such as intensity and retinal
      eccentricity. We assessed the capability of subjects to perceive simultaneity
      correctly despite these variations. Temporal asynchronies of up to 200 ms were
      introduced between the components of sound/light pairs. Using the method of
      constant stimuli, seven subjects judged which came first. Distance, and hence the
      times of arrival of paired visual and auditory targets, was varied from 1 to 32
      m. Visual intensity was varied by viewing the target through 1.8 dB attenuating
      glasses, and a retinal eccentricity of 20 degrees was compared to central
      presentation. Despite large differences in reaction times, which varied in a
      predictable way with the stimulus parameters, the timing of sound/light pairings
      judged as simultaneous corresponded to when the light and sound left the source
      simultaneously. Almost complete compensation was found in all conditions tested,
      showing that these substantial but predictable variations in timing can be taken
      into account in creating simultaneity constancy.

PMID- 15560508
TI  - Time-shrinking: the process of unilateral temporal assimilation.
AB  - Our previous research on auditory time perception showed that the duration of
      empty time intervals shorter than about 250 ms can be underestimated hugely if
      they are immediately preceded by shorter time intervals. We named this illusion
      'time-shrinking' (TS). This study comprises four experiments in which the
      preceding interval, t1, was followed by a standard interval, t2. When t1 < or =
      200 ms, and t1 < or = t2, the underestimation of t2 came into view clearly. The
      absolute difference between t2 and t1 was the crucial factor for the illusion to
      appear. The underestimation increased when t2 increased from t1 to t1 + 65 ms,
      stayed at about 45 ms when t2 was between t1 + 65 ms and t1 + 95 ms, and
      disappeared suddenly when t2 exceeded t1 + 95 ms. This pattern of results was
      observed across all values of t1 < or = 200 ms. A model was fit to the data to
      elucidate the underlying process of the illusion. The model states that the
      perceived duration difference between t1 and t2 is reduced by cutting mental
      processing time for t2; in other words, that t2 assimilates to t1.

PMID- 15560509
TI  - The development of distance estimation in optic flow.
AB  - In three experiments we tested the ability of children aged 8 to 12 years and
      adults to locate a target in an optic texture flow projected onto the ground.
      During the exposure phase, a static target (diode) was lit up at 6 m or 8 m on
      the ground in front of the subject. During the pointing phase, the subject was
      asked to indicate the perceived location of the target with a laser pointer as
      soon as the target was switched off. In the first experiment, during both phases
      the optic texture (environment) was either motionless or approaching the subject.
      Results showed that target locations were significantly more underestimated
      within the moving texture than within the still texture. In the second
      experiment, a detailed error analysis showed that the differences of performance
      between children and adults were not due to differences in eye height. Errors can
      be described by a linear fit with the retinal speed of the optic flow surrounding
      the targets. Distance judgments improved from the age of 8 years onwards. In the
      last experiment we found the same kind of results with a receding texture and
      without stimulation in central vision. Results are discussed in terms of
      subject's capacity to compensate for the effect of linear vection produced by the
      optic flow.

PMID- 15560510
TI  - Psychophysics with junctions in real images.
AB  - Junctions, formed at the intersection of image contours, are thought to play an
      important and early role in vision. The interest in junctions can be attributed
      in part to the notion that they are local image features that are easy to detect
      but that nonetheless provide valuable information about important events in the
      world, such as occlusion and transparency. Here I test the notion that there are
      locally defined junctions in real images that might be detected with simple,
      early visual mechanisms. Human observers were used as a tool to measure the
      visual information available in local regions of real images. One set of
      observers was made to label all the points in a set of real images where one edge
      occluded another. A second set of observers was presented with variable-size
      circular subregions of these images, and was asked to judge whether the regions
      were centered on an occlusion point. This task is easy if junctions are visible,
      but I found performance to be poor for small regions, not approaching ceiling
      levels until observers were given fairly large (approximately 50 pixels in
      diameter) regions over which to make the judgment. Control experiments ruled out
      the possibility that the effects are just due to junctions at multiple scales.
      Experiments reported here suggest that, although some junctions in real images
      are locally defined and can be detected with simple mechanisms, a substantial
      fraction necessitate the use of more complex and global processes. This raises
      the possibility that junctions in such cases may not be detected prior to scene
      interpretation.

PMID- 15560511
TI  - Experiments with a hollow mask and a reverspective: top-down influences in the
      inversion effect for 3-D stimuli.
AB  - Earlier psychophysical and physiological studies, obtained mostly with two
      dimensional (2-D) stimuli, provided evidence for the hypothesis that the
      processing of faces differs from that of scenes. We report on our experiments,
      employing realistic three-dimensional (3-D) stimuli of a hollow mask and a scene,
      that offer further evidence for this hypothesis. The stimuli used for both faces
      and scenes were bistable, namely they could elicit either the veridical or an
      illusory volumetric percept. Our results indicate that the illusion is weakened
      when the stimuli are inverted, suggesting the involvement of top down processes.
      This inversion effect is statistically significant for the facial stimulus, but
      the trend did not reach statistical significance for the scene stimulus. These
      results support the hypothesis that configural processing is stronger for the 3-D
      perception of faces than it is for scenes, and extend the conclusions of earlier
      studies on 2-D stimuli.

PMID- 15560512
TI  - Task-dependent changes of the psychophysical motion-tuning functions in the
      course of perceptual learning.
AB  - In some cases, perceptual learning is task-specific. However, task-dependent
      effects of perceptual learning on psychophysical motion-tuning functions have yet
      to be clarified. In the present study, subjects performed motion detection or
      discrimination of the same stimulus over the course of four sessions held on
      separate days. Subjects who performed motion detection showed the most highly
      improved performance on the trained motion directions. However, after
      discrimination training, the highest improvement was not observed at the trained
      directions but shifted away from them. These results can be explained by lateral
      inhibition. Task demands may differentially modulate excitatory and inhibitory
      signals to directions in the vicinity of the trained directions.

PMID- 15560513
TI  - Performance of community-based animal health workers in the delivery of livestock
      health services.
AB  - Since the liberalization of animal health services in Kenya in the early 1990s,
      community-based animal health workers (CBAHWs) have become an important
      alternative animal health delivery channel in the country's marginal areas.
      However, professional veterinary practitioners have questioned the effectiveness
      of CBAHW programmes in animal health service delivery in Kenya. This is partly
      due to lack of information about their performance and partly because CBAHW
      programmes were implemented before the necessary changes in the existing legal,
      policy and institutional frameworks had been made. This study was designed to
      provide such information. In this regard, the productivity of livestock herds
      among farmers who utilized the services of CBAHWs was compared to that of
      livestock belonging to farmers who utilized the services of professional
      veterinarians. The annual live births per mature female (birth ratio) and the
      proportion of young stock to mature females (breeding index) was computed over a
      period of 3 years in cattle and goat herds under care of CBAHWs and professional
      veterinarians. The birth ratios in cattle and goats under CBAHWs were not
      significantly different from those under the care of professional veterinarians
      (p > 0.05). Furthermore, the breeding index of cattle and goats under the two
      categories was not statistically different. Besides the CBAHWs providing clinical
      services, they also created positive externalities through participatory learning
      enjoyed by neighbouring livestock keepers, who later dispensed with their
      services. Policy attention is therefore needed to enhance the participation of
      CBAHWs in animal health service delivery and to appropriately integrate their
      activities into the existing formal animal health delivery system in Kenya.
      Interventions that improve the professional development of these workers, with
      emphasis on areas pertaining to care of young stock, would not only promote the
      sustainability of CBAHW programmes but would also improve livestock productivity
      in the country's marginal areas.

PMID- 15560514
TI  - Evaluation of abattoir inspection for the diagnosis of Mycobacterium bovis
      infection in cattle at Addis Ababa abattoir.
AB  - Detailed postmortem examinations were conducted to evaluate the efficiency of
      meat inspection procedures and to determine the distribution of lesions in
      Mycobacterium bovis-infected cattle. The study involved routine inspection at
      slaughter, collection of tissues for detailed examination in the laboratory, and
      bacteriological examination to identify M. bovis. Additionally, a 10-year (1992-
      2001) meat inspection record was analysed to determine tuberculosis trends in the
      past decade. chi2-Test and simple regression were used to analyse the data. Out
      of 1350 cattle examined, 1.5% were found with tuberculous lesions. Routine
      abattoir inspection detected only 55% of cattle with confirmed lesions. Fifty
      four per cent of tuberculous lesions were found in the lungs and thoracic lymph
      nodes, 23% in the lymph nodes of the head, and the remaining 23% in the
      mesenteric and other lymph nodes of the carcase. M. bovis was additionally
      isolated from an animal that had no gross lesions of tuberculosis. On average,
      the annual rate of whole-carcase condemnation due to generalized tuberculosis was
      0.024% and it has increased annually by 0.34% over the past decade. The rate of
      whole-carcase condemnation indicates a high degree of TB transmission and
      requires immediate attention from both the economic and public health points of
      view. The lower sensitivity of routine abattoir inspection confirms the
      importance of improving necropsy procedures.

PMID- 15560515
TI  - Protein and energy requirements of pre-weaned West African dwarf goats fed
      soyabean diet as a replacement for milk in a tropical environment.
AB  - Twenty-one early-weaned West African dwarf goats weighing between 1.0 and 1.5 kg
      at birth were used to assess the protein and energy requirement of pre-weaned
      West African Dwarf (WAD) goats fed soyabean diet. Three isonitrogenous diets
      (24%) were prepared such that dried whole-milk protein was replaced by corn
      starch and soyabean concentrate protein at 0.0%, 25.0% and 50.0% levels such that
      a 14.5% total solid solution was obtained for each diet. Results indicated that a
      daily digestible energy (expressed as kcal/day/W0.75 kg) intake of 58.2, 63.7,
      98.5 and 114.6 kcal was required for maintenance, while a corresponding value of
      7.37, 4.50, 2.18 and 1.91 kcal was required per day per gram live weight gain by
      the kids at 4, 6, 9 and 13weeks old, respectively. Similarly, a digestible crude
      protein (DCP) intake of 3.59 g/day/W0.75 kg) appeared to be adequate for
      maintenance of the kids between 0 and 13 weeks, while 0.34 g/day/W0.75 kg of DCP
      intake was required per day per gram live weight.

PMID- 15560516
TI  - Superovulatory response and embryo recovery after treatment with different
      gonadotrophins during induced luteal phase in Camelus dromedarius.
AB  - Superovulation, embryo recovery and transfer were attempted in 19 dromedary
      camels of about 6-10 years of age, and having calved at least once.
      Superovulation was done using two commercially available porcine FSH
      preparations, FSH-I (II donors) and FSH-2 (8 donors) during a luteal phase
      created by inducing ovulation with hCG. The superovulatory response was assessed
      by ultrasonography. The embryo recovery was attempted non-surgically in sitting
      position on day 8 and day 7 after first mating in one FSH-1 and one FSH-2 group,
      respectively. Considerable individual variation in response to the superovulatory
      stimulus was observed. No significant difference was observed between the two
      groups in terms of superovulatory response and embryo recovery (p > 0.05). In
      total 30 embryos were recovered from 17 donors (1.51 embryos/donor). Recipients
      were synchronized with donors using hCG. Eight embryos were transferred,
      resulting in two pregnancies and live births.

PMID- 15560517
TI  - The role of bioactive tannins in the postpartum energy retention and productive
      performance of goats browsed in a natural rangeland.
AB  - The role of bioactive tannins in browse in the postpartum performance of goats
      grazed under natural range conditions was studied using 40 yearling Mubende goats
      (20+/-0.32 kg). In a completely randomized design, goats of one group (n = 20)
      received a daily drench of 50 g per goat of polyethylene glycol (PEG) of
      molecular weight 4000 given as a condensed tannin (CT) deactivator, and goats of
      the other group (n = 20) acted as the control (no PEG). Mean birth weights, live
      weight gains, abortion and twinning rates, litter size and tissue energy
      retention were measured. The PEG drench resulted in lower postpartum weight gains
      and tissue energy retention (p < 0.05). Postpartum weekly weight loss per doe was
      0.65 kg in the PEG group and 0.46 kg in the control group, while tissue energy
      loss was 17.7 MJ per goat in the PEG group and 10.23 MJ per goat in the control
      group in the first 8 weeks. Net weight gain was observed in the control group at
      the 11 th week but was delayed in the PEG group (15th week). The PEG group had
      lower birth weights and higher kids mortalities (p <0.05). Selective feeding in
      the Ankole rangeland exposes goats to beneficial concentrations of dietary CT
      with apparent cumulative effects leading to improved postpartum performance of
      does and kids.

PMID- 15560518
TI  - Risk indicators associated with subclinical mastitis in smallholder dairy cows in
      Tanzania.
AB  - Smallholder dairy farmers in Tanzania appear to be unaware of the subclinical
      mastitis situation in their cows. A cross-sectional study was carried out between
      June and September 2002 on smallholder dairy herds in the Dar es Salaam region.
      The study objectives were to establish the prevalence of subclinical mastitis and
      related risk indicators, and to assess their contribution to the occurrence of
      subclinical mastitis. Three field procedures based on the principles of herd
      health and production management were followed: clinical, farm and data
      inspection. The California mastitis test (CMT) was carried out on quarter milk
      samples to determine the prevalence of subclinical mastitis. A total of 182
      lactating cows from 62 herds were investigated. Clinical inspection indicated
      that 3.8% of the lactating cows had clinical mastitis. Subclinical mastitis was
      detected in 90.3% of lactating cows screened. Farm inspection revealed that water
      scarcity, barn size, residual suckling, single udder-towel and dairy labourers as
      the most substantial (p < 0.05) risk indicators. Although most of the risk
      indicators studied were not found to be statistically significantly associated
      with the occurrence of subclinical mastitis, possibly owing to sample size and
      the presence of confounders, the epidemiological need to address such risk
      indicators cannot be overemphasized.

PMID- 15560519
TI  - Evaluation of Gmelina arborea leaves supplemented with grasses (Panicum maximum
      and Pennisetum purpureum) as feed for West African dwarf goats.

PMID- 15560520
TI  - Effect of early weaning, split-weaning and nursery feeding programmes on the
      growth of Landrace x Desi pigs.
AB  - An experiment using 164 crossbred pigs born to 20 first-parity sows was conducted
      to evaluate the growth performance of piglets in four weaning management
      regimens: T1, conventional weaning at 56 days; T2, early weaning at 28 days; T3,
      split-weaning of the heavier half of the litter at day 28, the remaining half
      being weaned at 56 days; and T4, split-weaning of the lighter half of the litter
      at 28 days, with the animals kept on a special nutrient diet up to 56 days, and
      the heavier half being weaned at 56 days. Split-weaning of the lighter half in
      combination with feeding a special nutrient diet resulted in an increase of
      average daily gain of 21% from day 28 to day 140 compared to conventional weaning
      and of 36% compared to early weaning at day 28. Compared to the control (T1), the
      average weights of piglets at the 140th day in groups T4 and T3 were 19.6% and
      6.16%, respectively, higher, whereas that of the T2 was 8% lower. It is concluded
      that feeding a special nutrient diet to lighter pigs is beneficial in overcoming
      the post-weaning lag and enables maximal weight gain.

PMID- 15560521
TI  - Dynamic modelling of a traditional African chicken production system.
AB  - A dynamic stochastic model, SimFlock, was developed with the purpose of
      simulating the dynamics of a traditional African chicken flock at smallholder
      level. The model simulates outputs, e.g. total number of chickens produced, egg
      production and net return after entering flock, or area-specific biological
      parameters. Biological parameters include hatchability, egg production, growth
      and survival of various age groups, full-grown weights as well as some decision
      parameters like farmers' need for meat consumption, and slaughtering and selling
      age of chickens. A simulation job is defined by 'states of nature' (biological
      parameters specified directly or drawn at random from the hyperparameters),
      number of replications and number of days to be simulated. Three simulation jobs
      were selected to demonstrate the use of the model: one with the default settings;
      one with collection of eggs for 20 days; and one in which growth rate was
      increased to double. After simulation, the results of each job were compared in
      relation to total number and weight of chickens produced, egg production and net
      return. SimFlock could be used as a management or extension tool to identify the
      biological parameters of major influence on production. Improvement of these
      parameters will have the largest impact on output.

PMID- 15560522
TI  - Brian A. Croft--a tribute.

PMID- 15560523
TI  - Classifying life-style types of phytoseiid mites: diagnostic traits.
AB  - Several traits are useful for identifying life-style types of predaceous
      phytoseiid mites when either 2 (diet generalist-specialist) or 4 (specialist I
      and II-generalist III and IV) type models [McMurtry J.A. and Croft B.A. 1997.
      Annu. Rev. Entomol. 42: 291-321] are considered. Traits useful for both models
      are developmental time and oviposition rates when feeding on several food types.
      Discriminating for the 2-types model are dorsal shield setae lengths, and intra-
      and inter-specific predation. Another trait useful for both models is feeding
      preferences of adult female phytoseiids on eggs versus larvae of Tetranychus
      urticae Koch. In this paper, we review established and other traits that need
      more study such as mouthpart types, other morphological features, spider mite
      webbing effects, distributions relative to prey-foods, plant-host relationships
      including domatia and sap feeding, density-dependent responses to prey and
      predator-prey ratios required for biological control. Uses of life-style data in
      biological control decision-making are discussed.

PMID- 15560524
TI  - Evaluation of prey-stage preference as an indicator of life-style type in
      phytoseiid mites.
AB  - Discriminant analysis (DA) models were developed and applied to examine the use
      of prey-stage preference (Tetranychus urticae Koch egg versus larval prey) in the
      classification of phytoseiid mites into life-style types. Prey-stage preferences
      and developmental times when preying on T. urticae, and relative ovipositional
      rates on six food categories were determined for four phytoseiid species
      occurring on apple in central and eastern Oregon, USA: Galendromus flumenis
      (Chant), Galendromus occidentalis (Nesbitt), Metaseiulus citri (Garman and
      McGregor) and Typhlodromus caudiglans Schuster. In terms of all three aspects
      studied, the phytoseiid species showed a consistent polarization of G.
      occidentalis < or = G. flumenis < or = T. caudiglans < M. citri. Specifically, G.
      occidentalis ('The Dalles' strain) had a significant preference for eggs, G.
      flumenis had no preference, and T. caudiglans and M. citri had significant
      preferences for larvae; G. occidentalis had the shortest developmental time,
      followed by G. flumenis and T. caudiglans, while M. citri had the longest
      developmental time; and diet breadth was most narrow for G. occidentalis and
      progressively broader from G. flumenis, T. caudiglans through M. citri, which was
      able to sustain oviposition on the broadest range of prey and pollens. Species
      were classified somewhat differently depending on which traits were considered in
      a given DA. Prey-stage preference was not included as an indicator in the
      parsimonious DA model when all species and all traits were considered, but in
      general this trait performed well as an indicator alone (single-trait DA) and
      somewhat improved the classifications of multitrait discriminant analyses.

PMID- 15560525
TI  - Phytoseiid mites on unsprayed apple trees in Oregon, and other western states
      (USA): distributions, life-style types and relevance to commercial orchards.
AB  - In unsprayed apple trees in eastern Oregon, Galendromus flumenis (Chant),
      Galendromus occidentalis (Nesbitt), Typhlodromus caudiglans Schuster and
      Metaseiulus citri (Garman and McGregor) were common phytoseiid mites; common
      plant-feeding mites were the eriophyid, Aculus schlechtendali Nalepa, the brown
      mite, Bryobia rubrioculus (Scheuten) and Eotetranychus spp.; apple rust mites
      seemed to be the primary prey for phytoseiids; the spider mites, Tetranychus
      urticae Koch and Panonychus ulmi (Koch) were scarce except for a few local
      outbreaks; the stigmaeid Zetzellia mali (Ewing) was at 10% of sites and its
      densities were inversely related to phytoseiid densities; phytoseiids were absent
      at some sites, particularly at high elevations where winters are severe. In seven
      Oregon ecoregions, G. flumenis was often at lower elevations in valleys with
      moderate winters; T. caudiglans was often at higher elevations; G. occidentalis
      was often at intermediate elevations, in young trees, and near where pesticides
      were used; it dominated in unsprayed trees only in almost treeless, sage-covered
      areas; M. citri was usually in older apple trees near agriculture. In mixed
      phytoseiid populations, M. citri, a generalist, and G. occidentalis, a
      specialist, occurred more often than expected; G. occidentalis was mostly found
      with T. caudiglans, a generalist; G. flumenis, a generalist, occurred less with
      others, possibly because it competes with both specialists and generalists.
      Analyses of species' distributions with multiple regression and genetic models
      gave explanatory r2s of 0.019-0.318. Of 29 variables, altitude of site, intensity
      of agricultural management, tree age, plant types, and Z. mali levels helped
      explain phytoseiid species presence. In the western USA, G. flumenis dominated in
      middle-southern latitudes; T. caudiglans dominated in the north near the Canadian
      border; G. occidentalis dominated in middle latitudes in parts of Washington,
      Idaho, Montana, and Wyoming; M. citri was at a few sites in these four states.
      Distributional and independent variable data were used to predict species
      presence at sites in Oregon with a 70% success rate. We discuss phytoseiid life
      style types, community dynamics, presence in organic/conventional orchards, and
      trends as more selective IPM methods are used in apple orchards.

PMID- 15560526
TI  - Low-density releases of Neoseiulus fallacis provide for rapid dispersal and
      control of Tetranychus urticae (Acari: Phytoseiidae, Tetranychidae) on apple
      seedlings.
AB  - Releases of Neoseiulus fallacis (Garman) at 1500--6000 per ha when prey were at
      0.1-0.3 per leaf provided seasonal control of Tetranychus urticae Koch (all
      stages) at 1-2 per leaf in an apple seedling rootstock nursery. Predaceous mites
      (all stages) increased to 0.3-0.4 per leaf after releases and predator prey
      ratios of < or = 1:3-7 provided pest regulation thereafter. Such low-density
      releases were thought to be effective because multiple dispersal bouts allowed
      predators to locate widely distributed spider mites (on 2-6% of leaves). A random
      diffusion model simulating predator dispersal (incorporating wind speed and
      direction parameters) adequately explained movement and pest control patterns. An
      upright, dense, uniform planting of apple seedlings was an effective producer and
      recipient for dispersing predators and these attributes seemed to explain why
      biological control was so effective. Low-density releases of N. fallacis for
      control of T. urticae are predicted to be less effective on other crops with less
      prominent profiles and soil coverage.

PMID- 15560527
TI  - Correlation of immunochemical detection of HPV L1 capsid protein in pap smears
      with regression of high-risk HPV positive mild/moderate dysplasia.
AB  - OBJECTIVE: To immunostain Pap smears of high-risk (hr) HPV DNA-positive early
      squamous lesions for detecting HPV L1 protein. STUDY DESIGN: Routinely stained
      archival slides from 84 mild and moderate hrHPV DNA-positive dysplasias were
      immunostained using a panreactive HPV L1 antibody. Follow-up smears were taken
      from women with remission for a mean period of 22.8 months (range, 6-46).
      Conization was done in patients with persistence or progression (3 and 48
      patients, respectively) after a mean time of 12 months (range, 9-48). RESULTS:
      Twenty-nine of 84 smears (34.5%) had positively stained squamous epithelial cell
      nuclei. In 9 of 29 (31%) women progressive disease occurred (2 cervical
      intraepithelial neoplasia [CIN] 2 and 7 CIN 3 lesions on conization) 20 (69%) had
      remission. Of the 55 L1-negative cases, 13 (23.6%) had remission, 42 (76.4%)
      progressed (3 CIN 2, 38 CIN 3, 1 microinvasive carcinoma). The difference in
      follow-up between L1 positive and negative cases was statistically significant
      (chi2 test, p< or =0.001). CONCLUSION: Low and moderate dysplastic squamous
      lesions without immunochemically detectable HPV L1 protein are significantly more
      likely to progress than are L1-positive cases. Immunochemical L1 capsid detection
      in routine Pap smears thus offers prognostic information about early dysplastic
      lesions.

PMID- 15560528
TI  - Differentiation of bone and soft tissues in formalin-fixed, paraffin-embedded
      tissue by using methylene blue/acid fuchsin stain.
AB  - OBJECTIVE: To find a staining method for formalin-fixed, paraffin-embedded tissue
      that would distinguish bone from surrounding soft tissues, including muscle,
      periosteal tissue and bone marrow. STUDY DESIGN: A variety of stains were tested
      and compared with hematoxylin-eosin. The potential value of any given stain was
      evaluated based on its ability to stain bone and soft tissues different colors or
      shades that could be readily identified in photomicrographs. Stains were
      evaluated using both endochondral (tibia) and intramembranous bone (calvaria)
      samples. RESULTS: In contrast to standard hematoxylin-eosin stain, which stains
      both bone and soft tissues pink, the methylene blue/acid fuchsin stain
      demonstrates remarkable contrast between bone and other tissues. Methylene
      blue/acid fuchsin stained bone bright pink and the surrounding soft tissues blue
      purple. CONCLUSION: In addition to the superior staining properties of methylene
      blue/acid fuchsin, other benefits of this stain include its stability, ease of
      use and low cost. This stain has many potential applications in the study of
      erosive bone disease in humans and also in animal models for research.

PMID- 15560529
TI  - Tumor marker measurements of cells in a fine needle used for aspiration cytology.
AB  - OBJECTIVE: To investigate whether the needle washing could yield sufficient cells
      for tumor marker (TM) measurements as an ancillary technique to ensure the
      accuracy of fine needle aspiration cytology (FNAC) of tumors. STUDY DESIGN: After
      obtaining preliminary data that aspirated tumor cells within a 22-gauge needle
      could be collected by washing it with distilled water for TM measurements, we
      studied tumor cell numbers and TM values obtained by washing a 22-gauge needle
      directly after tumor aspiration and another needle after FNAC. RESULTS: Using 8
      resected hepatobiliary and pancreatic carcinomas, the used needles yielded 16.8+/
      10.5 x 10(4) cells per milliliter. Used needles from 6 adenocarcinomas expelled
      479.2+/-406.5 ng/mL of carcinoembryonic antigen, and 6,561.3+/-5,713.1 ng/mL of
      CA 19-9, while the needles from 2 hepatomas showed normal values of those
      markers. CONCLUSION: A needle used for FNAC contains sufficient cells for TM
      measurements, which can be ancillary to the differential diagnosis.

PMID- 15560530
TI  - Evaluation of applying feulgen stain for DNA analysis on destained hematoxylin
      eosin-stained cytologic smears.
AB  - OBJECTIVE: To evaluate the feasibility and reliability of DNA analysis performed
      on the original hematoxylin-eosin (HE)-stained cytologic specimens by destaining
      the slides and restaining with the Feulgen method. STUDY DESIGN: Image cytometric
      analysis of DNA ploidy status was performed in a comparative study on 20
      cytologic preparations from 10 nasopharyngeal carcinomas. Ten smears were stained
      directly by the Feulgen method, and the others were Feulgen stained after HE
      destaining. RESULTS: There was 90% overall concordance in DNA determination and a
      good correlation (r = .97, P < .001) between the DNA indices determined by the 2
      methods. Discordance was probably due to tumor heterogeneity. CONCLUSION: This
      study demonstrated that image cytometric DNA analysis on previously routinely HE
      stained cytologic preparations is feasible and reliable. This method permits
      retrospective studies on archival cytologic material from patients with long term
      follow-up data.

PMID- 15560531
TI  - Diagnostic value of CA 15-3 antibody in detecting metastatic adenocarcinoma.
AB  - OBJECTIVE: To determine the diagnostic value of CA 15-3 in detecting metastatic
      adenocarcinoma in body fluids using PreservCyt solution (Cytyc Corp., Boxborough,
      Massachusetts, U.S.A.) as collection fluid. STUDY DESIGN: Cytospin slides
      prepared from 72 cases with unequivocally benign or malignant diagnosis were
      studied. Of the cases studied, 34 were breast carcinomas, and 17 were benign
      pleural effusions. Slides were stained for CA 15-3 by using the avidin-biotin
      complex method. Cases were evaluated for the presence of membranous or
      cytoplasmic staining. The percentage of cells exhibiting strong staining was
      estimated for both breast carcinoma and all adenocarcinomas as a group. These
      results were compared with CA 15-3 staining exhibited by benign mesothelium.
      RESULTS: Ninety-one percent of the breast cancer cases studied showed a positive
      reaction with CA 15-3, while 6% of the benign mesothelium cases were positive (p
      < 0.01). The sensitivity of CA 15-3 was 91 % for breast carcinoma and 80% for all
      adenocarcinomas. Specificity was 94% for breast carcinoma and for all
      adenocarcinoma. CONCLUSION: CA 15-3 is a sensitive and specific marker for
      diagnosing adenocarcinoma in cytologic specimens using PreservCyt solution as
      collection fluid.

PMID- 15560532
TI  - Bone marrow angiogenesis and proliferation in B-cell chronic lymphocytic
      leukemia.
AB  - OBJECTIVE: To assess angiogenesis and the proliferative activity of bone marrow
      in patients with chronic lymphocytic leukemia (CLL) in relation to the bone
      marrow infiltration pattern. STUDY DESIGN: Bone marrow samples were obtained by
      trephine biopsy from 46 patients with B-cell CLL (B-CLL). Infiltration pattern
      was diffuse in 20 patients and nondiffuse--i.e., nodular, interstitial or mixed-
      in the remaining 26 patients. Ten normal bone marrow samples were used as a
      control group. Studies were carried out by immunohistochemical staining of
      paraffin-embedded bone marrow samples. Angiogenesis was assessed in the zones of
      highest vascular density (hot spots), visualized by the expression of endothelial
      antigen CD34 and expressed as a number of microvessels per high-powerfield (hpf)
      (final magnification, 400x). Proliferative activity was estimated by the
      expression of nuclear protein Ki-67, cyclin A and mean number of nucleolar
      organizer regions (AgNORs). RESULTS: Microvessel density was higher in B-CLL
      marrow than in normal marrow (30.1 and 16.44 per hpf, respectively) and was
      higher in the diffuse than nondiffuse pattern (33.6 and 27.5 per hpf,
      respectively). B-CLL bone marrow also showed higher proliferative activity, as
      assessed by mean number of AgNORs, than did normal marrow (1.52 and 1.25,
      respectively) and a higher mean percentage of cyclin A-positive cells (7.5 and
      6.8, respectively). In contrast, mean Ki-67 expression was similar in B-CLL and
      the control group. Mean AgNORs number, Ki-67 and cyclin A-positive cell
      percentage were significantly higher in B-CLL marrow with a diffuse as compared
      to nondiffuse involvement pattern (AgNORs, 1.75 and 1.35; cyclin A, 9.27% and
      3.95%; Ki-67, 34.9% and 23.3%, respectively). CONCLUSION: Our results indicate
      enhancement of bone marrow angiogenesis in B-CLL and a relationship between
      microvessel density and the bone marrow infiltration pattern. The study points
      also to a possible relationship between the bone marrow infiltration pattern and
      proliferative activity of bone marrow cells.

PMID- 15560533
TI  - Flow cytometric analysis of DNA indices, expression of p53 and multidrug
      resistance genes in multiple myeloma patients.
AB  - OBJECTIVE: To perform a quantitative analysis of DNA ploidy, S-phase fraction %
      (SPF%), p53 and multidrug resistance (MDR) gene expression as independent
      prognostic parameters and to compare these parameters with stage of the disease
      in multiple myeloma (MM) patients. STUDY DESIGN: Peripheral blood bone marrow
      samples were analyzed for DNA ploidy and SPF% using a FACScan flow cytometer
      (Becton Dickinson). Detection of p53 and MDR gene expression was done using
      immunocytochemistry. RESULTS: Aneuploidy was found in 5/48 (10.42%) total myeloma
      patients, all of whom revealed hyperdiploidy. High SPF% was noted in 18/37
      (48.65%) newly diagnosed MM patients and 5/11 (45.45%) follow-up cases of
      myeloma. p53 Gene product was noted in 8/48 (16.66%) myeloma patients, 6 newly
      diagnosed and 2 on follow-up. MDR gene expression was detected in 4/27 (10.81%)
      newly diagnosed patients and in 1/11 (9.09%)follow-up patients. CONCLUSION: All
      myeloma patients with aneuploidy revealed hyperdiploidy. The majority of cases
      with high SPF% were at advanced stages, indicating the prognostic significance of
      SPF%. Although, there was no statistical significance of DNA ploidy, SPF%, p53
      and MDR gene product expression, they are important prognostic parameters. Our
      results can provide baseline data for comparison with future studies since these
      parameters have not been reported earlier from the Indian subcontinent.

PMID- 15560534
TI  - DNA content as a prognostic marker of oral lichen planus with a risk of cancer
      development.
AB  - OBJECTIVE: To assess the presence of aneuploidy in oral lichen planus (OLP) and
      its usefulness as a prognostic marker. STUDY DESIGN: Eighty-one formalin-fixed,
      paraffin-embedded biopsy samples taken from atrophic-erosive OLP from 70 patients
      were studied. Approximately 150 random nuclei in basal and/or parabasal epithelia
      were analyzed with static cytometry. RESULTS: Aneuploidy was detected in 41% of
      samples. OLPs with ulcerations or location in the tongue had significantly higher
      values, respectively, for the 2.5c exceeding rate (ER) (p<0.001 and 0.001) and
      proliferation index (PI) (p = 0.012 and 0.013) than did lesions without
      ulcerations or at other locations. 2.5c ER was significantly higher in dysplastic
      OLP lesions (p < 0.001), and the significant value (p = 0.001)for 2.5c ER
      discriminating DNA aneuploidy was 15.3%. In multivariate analysis only the G2/M
      ER (G2/MER) was a significant independent predictor of developing cancer in OLP
      (OR 2.349, 95% CI 1.39-3.97, p = 0.001). CONCLUSION: Ulcerated atrophic-erosive
      OLPs of the tongue and with dysplasia are at increased risk of cancer
      development. 2.5c ER, PI and G2/MER might be useful in prognosticating the
      increased risk of malignancy in OLP.

PMID- 15560535
TI  - Prognostic value of morphometry in low grade papillary urothelial bladder
      neoplasms.
AB  - OBJECTIVE: To analyze the prognostic value of morphometry in low grade papillary
      urothelial bladder neoplasms (LGPUBNs). STUDY DESIGN: The primary (most common)
      and secondary (second most common) histologic grades were considered in
      accordance with the 1998 World Health Organization/International Society of
      Urological Pathology and the 1999 World Health Organization classifications. With
      the primary grade, 54 cases were papillary urothelial neoplasms of low malignant
      potential (PUNLMPs) and 66 low grade papillary urothelial carcinomas (LGPUCs),
      whereas the secondary grade consisted of 45 PUNLMPs and 75 LGPUCs. To assess the
      proliferative index, an immunohistochemical study was performed. Regarding
      nuclear morphometry, an image analysis system on Feulgen-stained sections was
      utilized in different tumor zones (Zs): Z 1, 100-150 cells from the outer layers
      of the papillae; Z 2, 100-150 cells from the inner layers; and Z 3, 10 largest
      nuclei. In univariate studies, a t test, and Mann-Whitney U test and Kaplan-Meier
      curves were applied, whereas a Cox regression model was used for multivariate
      study of the variables: size, multiplicity, maximum Ki-67 index, mean nuclear
      area (MNA) and SD, mean nuclear perimeter and SD, and roundness factor. RESULTS:
      All 120 cases were followed for a mean of 76.6 months (range, 36-168). In
      univariate studies, many variables showed a significant correlation (p < 0.05)
      with recurrence prediction, relapse-free interval and histologic grade regardless
      of adjuvant therapy. Otherwise, only the MNA of the 10 largest nuclei (threshold,
      52 microm2) and the maximum proliferative index (threshold, 7.9%) appeared as
      independent prognostic markers in the multivariate study. CONCLUSION: In LGPUBNs,
      the independent prognostic value of MNA of the 10 largest nuclei as well as the
      maximum proliferative index indicates the importance of histologic grade
      assessment based on the secondary (second most common) grade.

PMID- 15560536
TI  - High-risk HPV detection by Hybrid Capture and ploidy determination by a computer
      assisted system in cervical biopsies.
AB  - OBJECTIVE: To correlate high-risk HPV (hrHPV) detection by Hybrid Capture II
      (HC2) (Digene, Gaithersburg, Maryland, U.S.A.) with DNA content (ploidy) of
      cervical biopsies analyzed by a computer-assisted system. STUDY DESIGN: Cervical
      biopsies from 54 women examined at Leonor Mendes de Barros Hospital, Sao Paulo,
      as part of the Latin American Screening study during 2002--2003, were tested for
      hrHPV with HC2. All patients had been referred for colposcopic examination due to
      an abnormal cervical cytology. The final diagnosis included 30 cervicitis, 14
      cervical intraepithelial neoplasia (CIN) 1, 5 CIN 2, 4 CIN 3 and 1 squamous cell
      carcinoma (SCC). Five-micrometer sections of each biopsy were stained with
      Feulgen-tionine and evaluated with the CAS 200 System (Becton Dickinson, U.S.A.),
      using the 3.0 software (version 8.1) of the DNA Quantitative Measurement Program
      (Becton Dickinson). Ploidy was evaluated from histograms obtained by analyzing
      atypical nuclei. RESULTS: Of the 30 cervicitis cases, 28 (93.3%) were diploid,
      and hrHPV was detected in 8 (28.5%) of the cases. Two tetraploid cervicitis
      lesions were observed, 1 positive and 1 negative for hrHPV. Among the CIN 1
      lesions, 8 (57.1%) were diploid and 6 (42.8%) aneuploid. Of the latter, 4 (66.6%)
      were negative and 2 (33.3%) positive for hrHPV. Of the 5 CIN 2 lesions, 2 were
      diploid, 2 aneuploid and 1 tetraploid; all were positive for hrHPV. All CIN 3
      lesions and the SCC proved to be aneuploid and positive for hrHPV. CONCLUSION:
      The data suggest that the majority of cervicitis and CIN 1 lesions are diploid
      and negativef or hrHPV. This is in sharp contrast to high grade CIN 2-3 lesions,
      all of which were positive for hrHPV in this study and also aneuploid, consistent
      with their progressive potential.

PMID- 15560537
TI  - [Acute confusional state in hospitalized patients].
AB  - Delirium or acute confusional status (ACS) is a common mental disorder found in
      hospitalized patients. A total of 278 patients were evaluated. Of these, 30
      (10.8%) developed ACS. The patients who developed ACS were 70 years of age or
      older, had history of stroke or dementia, as well as impairment in activities of
      daily living, and required enteral feeding more frequently. The infections and
      hip fracture were the most frequent reasons for hospitalization. The mortality in
      patients with ACS was significantly higher than in patients without ACS.

PMID- 15560538
TI  - [Cardiovascular response to mental and physical stress in hyper-reactive
      normotensive subjects. Beta blockade effect].
AB  - The aim of our study was to evaluate the cardiovascular reactivity in healthy
      normotensive subjects without medication, using mental and physical stress
      techniques: Stroop color word conflict test (SCWCT), anticipatory blood pressure
      response to exercise (ARE) and stress testing (ST). We analized the effects of a
      selective beta 1 betablocker: bisoprolol (B) on cardiovascular reactivity in our
      subjects (s). We studied 42 s, but only 30 (21 females and 9 males) were included
      who were hyperreactives. The mean age was 42.5 years. The higher values of
      systolic (SBP) and diastolic blood pressure (DBP) during the mental stress (MS)
      were taken as a measure of reactivity considering hyperreactive response an
      increase of 30 mm Hg or more and/or 15 mm Hg or more respectively. A prospective,
      randomized and double blind study on the effects of an oral daily doses of B (5
      mg) vs placebo (P) was performed. Statistical analysis was realized with the
      Fisher exact test. In the results, we could observed a lower sensitivity of ARE
      and ST vs SCWCT. The 15 s who recieved P followed hyperreactives but 6 of 15 s
      treated with B were non reactives (p<0.017). B showed a beneficial effect on the
      hyperreactivity in a significant number of s in relation with P and it could be
      useful for the prevention of a future hypertension.

PMID- 15560539
TI  - [Compliance with continuous positive airway pressure therapy in patients with
      sleep apnea/hypopnea syndrome].
AB  - Predictive factors and compliance level were evaluated in a group of patients
      with sleep apnea syndrome under CPAP treatment, assessing side effects and
      equipment condition: silicone interface (SI), mask-conectors (M-C), air tube (AT)
      and head strap (HS). Patients with >3mo treatment were included, clock counter
      reading was registered at the beginning, 2 and 4 mo. Patients were considered
      compliant (C+) when usage was >4h/day and >5day/week. Of 46 patients (male 34;
      age 62 +/- 9years; BMI 33 +/- 7kg/m2; AHI 38 +/- 18/h; time of therapy 2.1 +/-
      1.7years; CPAP 9 +/- 1.4 cmH2O), 34 had a clock counter and 24 (71%) were C+.
      Initial symptoms included: somnolence (65%), snoring (39%), bed-partner witnessed
      apneas (28%). Comparing C+ and C- we didn't find significant difference in age,
      BMI, CPAP pressure, length of therapy, AHI and pre-treatment Epworth
      classification. Referred vs. measured time of use in C+ and C- were 6.6 +/- 1 vs.
      6.1 +/- 1 h/d (p=0.02) and 5.6 +/- 1 vs. 2.4 +/- 1 h/d (p<0.005). Compliant
      patients reported more resolution of somnolence (p<0.005) and nocturia (p<0.05),
      lower post CPAP Epworth (p<0.05), more frequent somnolence as initial symptom
      (p<0.05) and a higher education level (p=0.01). Side effects (SE) (n=45): dry
      mouth 36%, nasal congestion 27%, sleep disruption 11%, CPAP noisy 9%, dry nose,
      rhinorrhea and skin irritation 7%. Twenty seven percent of patients reduced the
      CPAP use because of the SE. Correction strategies included: humidifier, nasal
      steroid, surgery or infiltration of turbinates. Comparing the condition of SI, M
      C, AT and HS between < or =1 vs. >1year of use, we observed a lower percentage of
      fine elements (87 to 44%, 74 to 44%, 83 to 44%, 91 to 78%, respectively). Most
      common defects included stiffness of SI, cracks in SI, M-C and AT, loose
      conexions. The study confirms the importance of objective monitoring in patients
      with CPAP. Side effects and equipment condition require special attention because
      this could affect an effective treatment.

PMID- 15560540
TI  - [Primary osteoporosis risk factors in women from Cordoba, Argentina].
AB  - Risk factors for osteoporosis were evaluated in women from Cordoba, Argentina.
      Female patients that consulted about diagnosis or treatment of osteoporosis from
      January 2000 to June 2002 were included. Secondary osteoporosis patients were
      excluded. Participants were studied using standardized questionnaire, clinical
      examination, biochemical analysis, and dual-energy X-ray absorptiometry (DXA).
      According to lumbar spine DXA results and WHO criterion, we considered 2 groups:
      Osteoporosis (T score < -2.5 standard deviation, SD) and Control (T score > or = 
      2.5 SD). One hundred and fifty five women (Osteoporosis Group: 47; CONTROL GROUP:
      108) were studied. In univariate analysis age, years from menopause, weight,
      smoking duration, estrogen replacement therapy duration, bilateral oophorectomy
      with hysterectomy, alkaline phosphatase levels, and Pouteau-Colles fractures were
      different between both groups. After multivariate analysis, including variables
      that were statistical different in univariate analysis, and considering
      osteoporosis as dependent variable, body weight (Odds Ratio, OR=0.92; CI 95% 0.87
      0.98), alkaline phosphatase (OR=1.01; CI 95% 1.00-1.02), years from menopause
      (OR=1.12; CI 95% 1.05-1.21), and Pouteau-Colles fractures (OR=15.15; CI 95% 1.68
      135.7) were independent risk factors for osteoporosis.

PMID- 15560541
TI  - Trends in pharmacotherapy for chronic airflow limitation in Argentina: 1992-2002.
AB  - Asthma and COPD mortality rates have decreased in Argentina. These trends might
      be the result of the way these conditions are being treated. The number of units
      for prescription and over-the-counter (OTC) drugs used to treat chronic airflow
      limitation in Argentina from 1992 through 2002 were analyzed. Units for drugs to
      treat chronic airflow limitation fell by 45% over the 11-year period (p < 0.0001)
      due to significant reductions for oral beta2-agonists (OBA) (down 73%),
      theophyllines (down 74%), oral steroids (OS) (down 66%) and inhaled short-acting
      beta2-agonists (ISABA) (down 28%). Market share for inhaled steroids (IS)
      increased from 2.6% to 11.7%, for inhaled ipratropium (IP) from 0.35% to 3.7%,
      for the combination of inhaled steroids with short-acting beta2-agonists
      (IS+ISABA) from 7.8% to 13%, and for inhaled IP combined with short-acting beta2
      agonists (IP+ISABA) it increased from 1.7% to 7.3%. Inhaled long-acting beta2
      agonists (ILABA) and leukotriene modifiers (LM) were rarely prescribed. The use
      of more specific inhaled therapies (IS, IP) increased significantly in accordance
      with recommendations for the treatment of asthma and COPD and this may explain
      the reduction in asthma and COPD mortality in Argentina.

PMID- 15560542
TI  - [Clinical, epidemiological and immunological study of patients coinfected with
      HIV and HTLV-1].
AB  - We studied the prevalence of antibodies against HTLV-1 among every HIV-infected
      outpatients assisted in our hospital between January 1st 2000 and June 30th 2003.
      We reviewed the epidemiological data, clinical findings, viral load and CD4 cells
      count, comparing coinfected with non HTLV-1 coinfected. We found a prevalence of
      HTLV-1 infection of 8.1% (23/282); 8.5% (12/141) in men and 7.8% (11/141) in
      women [[OR=0.91 (0.36<OR<2.3) p=0.8]; 12.4% (16/129) among patients users of
      illicit drugs and 4.6% (7/152) among non-users [OR=2.93 (1.09<OR<8.17) p=0.03];
      20.8% (16/77) in injecting drugs users (IDU) and 3.4% (7/205) in non-IDU patients
      [p=0.000006 OR=7.42 (2.71<OR<20.9)]. Ninety six patients (96/282) had history of
      AIDS defining diseases (ADD). No differences in the ADD were found among
      coinfected and no coinfected patients. No patient developed any disease relative
      to HTLV-1. The mean of CD4-cells among HTLV-1 coinfected with history of ADD
      naive patients (n=7) was 211 cells/ml, and 87.9 cells/ml among those not
      coinfected (n=55) [t-test=2.82; p=0.006]. The viral load was similar among every
      investigated group of patients. We found a high prevalence of HTLV-1 infection in
      HIV-infected patients (higher among IDU). The CD4-cell count of patients
      suffering from an AIDS defining disease was higher among HTLV-1/HIV coinfected
      patients than in singly HIV infected, this could show a grade of missfunction of
      CD4-cells in coinfected patients.

PMID- 15560543
TI  - [Non conventional virological markers in HIV-infected patients: T-HIV DNA, 2LTR
      HIV DNA and HIV RNA].
AB  - Highly active antiretroviral therapy (HAART) induces a persistent reduction of
      the plasmatic viremia, contributing to decrease mortality and morbidity of
      infected people with human immunodeficiency virus (HIV). Thus, viral load (VL) is
      the reference method to evaluate therapy effectiveness. However, even in the
      presence of efficient HAART viral eradication was yet not achieved. In this
      study, we analyzed the presence of total HIV DNA (T-HIV DNA), non-integrated DNA
      with 2LTR (2LTR-HIV DNA) and HIV RNA in a group of 55 HIV-positive subjects from
      Rosario City, with different clinical stages, with and without HAART. All markers
      were evaluated by PCR assays optimized in our laboratory that included
      colorimetric detection in microplate. HIV RNA clinical sensitivity was compared
      with a reference test, bDNA, resulting in 74% and 64% respectively, with an 85%
      of agreement. Thus, our HIV RNA assay could be used to monitor patients under
      HAART and at risk of infection. The 2LTR-HIV DNA was 54% positive although it was
      absent in patients with high VL. This marker was considered a labile product
      therefore its presence was associated with recent infection. However, current
      evidences question its stability. Thus, its clinical significance should be
      reconsidered. The absence of 2LTR-HIV DNA in patients with detectable VL may
      relate to the heterogeneity of the sequence used for its detection. T-HIV DNA was
      present in 100% of the samples and could be a relevant remission marker when
      therapies that effectively eradicate the infection became available.

PMID- 15560544
TI  - HBsAg as predictor of outcome in renal transplant patients.
AB  - Chronic liver infections related to hepatitis B and C viruses are a common
      problem in renal transplant patients with a prevalence of 1.5 to 50% in different
      countries. There is no uniform agreement regarding their influence on the
      incidence of acute rejection, graft outcome and survival of renal transplant
      patients. We retrospectively evaluated the influence of antiHBc, antiHCV and
      HBsAg positive status; gender; age over 50 years of age at the time of
      transplantation; pre and postransplantation alaninaminotransferase (ALT)
      elevation; acute rejection; type of graft; number of transplants; and maintenance
      and induction immunosuppression treatment on the incidence of acute rejection and
      both graft and patient survival in the population transplanted in our center
      between 1991 and 1998. The univariate analysis showed that antiHCV, HBsAg and
      antiHBc status, more than one renal transplant and one or more episodes of acute
      rejection were associated with diminished graft survival; and being over the age
      of 50 at the time of transplantation was also associated with diminished patient
      survival. In the multivariate analysis HBsAg positive and one or more episodes of
      rejection were associated with a diminished graft survival, and none of the
      variables studied was associated with diminished patient survival. In conclusion
      antiHCV and HBsAg positive status was associated with an increased risk of losing
      the transplanted kidney, and HBsAg positivity was associated with an increased
      risk of death, but this was not a statistically significant association.

PMID- 15560545
TI  - [Polymorphonuclear leukocytes decrease the immunostimulatry capacity of human
      dendritic cells].
AB  - The aim of this work was to evaluate the ability of polymorphonuclear leukocytes
      (PMNL) to modulate the function of dendritic cells (DCs). Human DCs were used to
      analyze the effect of PMNL on DCs. The allostimulatory proliferation of T cells
      induced by DCs incubated with PMNL was lower (42 +/- 14%, n:8, p<0.05) compared
      with untreated DCs. The decreased proliferation correlated with lower IFNgamma
      production (DCs: 781 +/- 3 pg/ ml; DCs-CS: 343 +/- 178 pg/ml, p<0.05). The same
      effect was observed in an antigen specific assay. However, the effect was not
      observed when PMNL where incubated with mature DCs. Indeed, the effect of PMNL
      was partially reverted with serine proteases inhibitors. Overall, these results
      suggest that PMNL modulates DCs activity by serine proteases.

PMID- 15560546
TI  - [The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy].
AB  - The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy.
      Tuberculoid leprosy patients locally produce Th1 cytokines, while lepromatous
      patients produce Th2 cytokines. Signaling lymphocytic activation molecule (SLAM)
      and the SLAM-associated protein (SAP) participate in the differentiation process
      that leads to the production of specific patterns of cytokines by activated T
      cells. To investigate the SLAM/SAP pathway in M. leprae infection, we determined
      the expression of SAP, IFN-gamma and SLAM RNA messenger in leprosy patients. We
      found a direct correlation of SLAM expression with IFN-gamma expression, whereas
      the expression of SAP was inversely correlated with the expression of both SLAM
      and IFN-gamma. Therefore, our data indicate that SAP might interfere with Th1
      cytokine responses while SLAM expression may contribute to Th1 responses in
      leprosy. This study further suggests that the SLAM/SAP pathway might be a focal
      point for therapeutic modulation of T cell cytokine responses in diseases
      characterized by dysfunctional Th2 responses.

PMID- 15560547
TI  - [Arrhythmogenic right ventricular dysplasia and sick sinus syndrome].
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) involves primarily the right
      ventricle, and should be considered in young patients presenting with syncope,
      ventricular tachycardia, cardiac arrest or in adults patients with congestive
      heart failure. Atrial electrical abnormalities due to ARVD have been rarely
      described. We report a case of ARVD in a 60-year-old man who developed sick sinus
      syndrome during evolution (sinus node recovery time of 6113 mseg). Atrial
      arrhythmias may be explained by gradual replacement of right atrium myocytes by
      adipose tissue.

PMID- 15560548
TI  - [Severe cardiac disease in scleroderma].
AB  - A 36 year-old female with a diagnosis of systemic sclerosis suffered from an
      acute episode of skeletal myositis and refractory heart failure with cardiogenic
      shock. Despite immunosuppressive treatment with high doses of corticosteroids and
      hemodynamic support she died five days after admission. The autopsy showed
      cardiac myocytolysis, myocyte necrosis and contraction band necrosis. There are
      very few reported cases of severe heart failure associated to systemic sclerosis.

PMID- 15560549
TI  - [Treatment of patients with chronic obstructive pulmonary disease (COPD) by
      primary care physicians].
AB  - A number of recommendations for the treatment of chronic obstructive pulmonary
      disease (COPD) present the different therapeutic alternatives according to the
      severity of the condition. It is not entirely clear when the generalist should
      consult the specialist. This can be important particularly when the health care
      system is centered in the role of generalists and lack of clarity may be a factor
      in the deficient use of recommendations. The purpose of this review is to provide
      evidence of the efficacy and effectiveness for therapeutic approaches distilling
      from randomized controlled trials, observational trials and guidelines or meta
      analyses. The emphasis is on the identification of clinical and physiological
      criteria that generalists should use to identify candidates for possible
      consultation with specialists.

PMID- 15560550
TI  - [Adhesion molecules. Their role in cardiovascular physiopathology].
AB  - Adhesion molecules are membrane receptors that mediate several functions related
      to cell traffic, cell-cell interactions, and cell-matrix contact. There are three
      important groups associated to cardiovascular disease: integrins, selectins, and
      the immunoglobulin superfamily. They are involved in the endothelial disfunction
      and activation processes, and are related to the pathogenesis of coronary artery
      disease, reperfusion injury, allograft vasculopathy, myocarditis, hypertrophic
      myocardiopathy, etc. Also, they are related to the mechanism of action of
      statins. Serologic titer of these molecules has diagnostic and predictive value
      on diverse cardiovascular diseases. This review focuses on the functions of
      adhesins and discusses various therapeutic possibilities based on their
      recognition.

PMID- 15560551
TI  - [Medicine, research and education].

PMID- 15560552
TI  - [Orthostatic cephalea].

PMID- 15560553
TI  - [Error in medicine].

PMID- 15560554
TI  - [Thyrotoxicosis and specific prostate antigen].

PMID- 15560555
TI  - Radiofrequency ablation of unresectable hepatic malignancies.
AB  - Since radiation and chemotherapy have little impact on survival and no prospect
      for cure, surgery offers the best potentially option in patients with liver
      tumors. However, a lot of patients with liver tumors is not resectable due to
      stage combined with health problems, or poor liver function reserve. In this
      study, our preliminary clinical reports in patients with unresectable liver
      tumors treatment with RFA have demonstrated radiologic evidence of tumor necrosis
      and complications. Multielectrode, radiofrequency probes were supplied by RITA
      Medical Systems (Mountain View, California). This study involved a total of 28
      liver tumors in 19 patients (including 17 patients with hepatomas and 2 patients
      with metastases). The mean age was 68.9 years old. The size of tumor was more
      than 3 cm in 15 patients. The approaches to the tumor were laparoscopic in 1
      patients and open surgical in 18 patients. Hepatic vascular occlusion was
      combined with RFA in 5 cases. The reasons for unresectable were defined as total
      bilirubin, ICGR 15, cardiopulmonary function and multiplicity. The efficacy of
      this RFA therapy was evaluated by preoperative and follow-up CT scans or tumor
      makers. There tumor necrosis was shown in 15 patients (78.9%). The survival rates
      at the time up to 12 months were 84.2% in 16 patients. The present study has
      demonstrated that the RFA is able to provide a safe and effective means in
      controlling liver tumors.

PMID- 15560556
TI  - [The value of resection in pancreatic cancer: the analysis of an experience of
      180 patients in 10 years].
AB  - Pancreatic cancer (PC) represents one of the most severe malignant diseases, with
      an extremely high mortality rate (80% in the first year following diagnosis). The
      only potentially curative treatment is resection. This report evaluates the last
      10-year experience in surgical resection for pancreatic cancer in the Center of
      General Surgery and Liver Transplantation from the Fundeni Clinical Institute
      (Bucharest--Romania), between 01.01.1995-01.05.2004. From a total of 832 patients
      with pancreatic cancer who were surgically treated, 180 underwent various
      resections (a resecability rate of 21.6%). There were 120 resections for cancer
      of the pancreatic head: 61 Whipple procedures, 10 pilorus preserving
      pancreaticoduodenectomies, 10 pancreaticoduodenectomies associated with complex
      resection, 17 pancreaticoduodenectomies with resection of the portal vein, 15
      pancreaticoduodenectomies with extensive lymphodissection, 2 subtotal
      pancreatectomies and 5 total pancreatectomies; 60 standard splenopancreatectomies
      were performed for cancer of the pancreatic tail. The overall morbidity was 34%-
      61 patients (38 with cancer of the pancreatic head and 23 with pancreatic cancer
      of the tail), with the prevalent complication represented by pancreatic fistula.
      The mortality rate was 6.6%--12 patients (9 with cancer of the pancreatic head
      and 3 with cancer of the tail); there was a continuous decreasing trend from 9.1%
      between 1994-1999 to 1.6% between 2002-2004. In our Center an increasing
      preoccupation for pancreatic surgery, along with an improved surgical experience,
      resulted in a constant raise in the number of patients resected for pancreatic
      cancer, with a low morbidity and mortality rate.

PMID- 15560557
TI  - [Surgical management of clinical problems in children with HIV infection].
AB  - HIV infection is a very actual disease widespread all over the world (40 million
      people), including up to 10 thousand Romanian, are infected with HIV; there are
      950 HIV-infected patients in Oltenia, 450 of them are in our county (Dolj area),
      80% of the HIV-infected persons are children. The authors are studying a group of
      17 cases of HIV-infected children with surgical problems (Acute appendicitis,
      acute cholecystitis, pulmonary and kidney abscess, lymphadenophlegmons, abdominal
      tumours), which have been transferred to our department from the Infectious
      Diseases Clinic, between 1995-2004. The medical records of all patients were
      reviewed: strategies of management, particularity of antiretroviral therapy of
      children, and also strategies of prevention the perioperative HIV transmission.
      The most frequent cases were the lymphadenophleg mons (40%) and chronic abdominal
      pain (25%). The acute abdominal pathology consisted in 2 cases of acute
      appendicitis and 1 case of acute cholecystitis, which were successfully treated.
      The HIV infection remains in actuality, because there is not an efficient
      antiretroviral therapy. Surgeons planning treatment must consider the risks of
      the patient against the potential benefits of surgery.

PMID- 15560558
TI  - [Meckel's diverticulum in laparoscopic era].
AB  - A recent case of a Meckel's diverticulum diagnosed and successfully
      laparoscopically treated, triggered off a retrospective study on a series of 34
      cases with Meckel's diverticulum admitted to the First Surgical Clinic between
      1990-2003. We encountered 12 uncomplicated cases and 22 cases with a large panel
      of complications: 11 intestinal obstructions (volvulus 9, intussusceptions on a
      tumor-2), 9 cases with diverticulitis, 1 gastrointestinal bleeding and 1 case
      with Littre's inguinal hernia. Positive diagnosis was established
      intraoperatively and the surgical treatment was adapted according to the local
      situation (excision of the diverticulum or enterectomy). Out of 12 patients with
      uncomplicated Meckel's diverticulum 8 were subjected to prophylactic excision of
      the diverticulum. In 6 of these microscopic examinations were inclusions of
      gastric mucosa. Laparoscopy is safe, relatively inexpensive and efficient in the
      diagnosis and treatment of Meckel's diverticulum.

PMID- 15560559
TI  - [Laparoscopic management of Meckel's diverticulum].
AB  - We present our observations on two young patients with repeated digestive
      bleeding from hemorrhagic Meckel's diverticulum. In one patient examined by Tc99
      scintigraphy, the hemorrhagic area was shown in the lower abdomen. The
      laparoscopic exploration showed the Meckel's diverticulum at 1 m distance from
      ileocecal angle. Both cases were treated by resection with a vascular stapler
      postoperative evolution was favorable.

PMID- 15560560
TI  - [Ileosigmoid fistula due to an abscess of a periappendicular mass].
AB  - The paper debates the subject of the undiagnosed acute appendicitis. The
      formation of a complex ileosigmoid fistula due to an abscess of the
      periappendicular mass and the three steps peritonitis determined a particular
      approach in solving the case.

PMID- 15560561
TI  - [The megaureter--a possible complication after resected retroperitoneal tumor].
AB  - The authors present a very rare complication of a retroperitoneal tumor
      resection: unilateral iliopelvic segmental megaureter. This condition was
      subsequently complicated with a diffuse peritonitis caused by parietal
      microperforations.

PMID- 15560562
TI  - [False surgical acute abdomen with intermittent acute porphyria].
AB  - This article presents a case of acute intermittent porphyria admitted to the
      Surgery Department of C.F. Craiova Hospital between 18.08.2003-26.08.2003 then
      transferred to the Colentina Hospital in Bucharest for diagnosis confirmation and
      adequate treatment. The purpose of this paper is to bring attention on a rare
      metabolic inherited disease that, due to its non-specific and often noisy
      symptoms and limited possibilities of biochemical, enzymatic and genetic
      diagnosis, could generate potential serious confusions. The presentes case
      illustrates the fact that sometimes the acute attack may be mistaken for an acute
      surgical affection which requires an emergency operation with all the aggravating
      consequences and delay in the real diagnosis. About 1% of acute attacks of
      porphyria may be fatal. Only the drugs known as safe should be prescribed. Basic
      treatment consists in oral and intravenous glucose and hematin administration.

PMID- 15560563
TI  - [Cystic lymphangioma of the adrenal gland].
AB  - Cystic lymphangioma of the adrenal gland is a rare tumor, which is often sub
      clinical. Preoperative diagnosis is difficult. We present a case of a 47 year-old
      female in whom an incidental left cystic mass of 12 cm by 10 cm with no features
      of malignancy was discovered by ultrasound scan. A further computed tomography
      scan confirmed the ultrasound findings. Biochemical screening ruled out a
      secreting adrenal tumor. Because of the size of the cyst, the lesion was resected
      and the diagnosis of benign adrenal cystic lymphangioma was histologically
      confirmed. Computed tomography is the reference examination for delineating the
      topography and extent of the lesion, especially when it is large. Although
      imaging can characterize the cystic nature of a lesion, it sometimes fails to
      establish a specific diagnosis, so surgery or fine needle aspiration should be
      done for a definitive diagnosis. The characteristic features of cystic adrenal
      lymphangioma are discussed together with a review of the recent literature.

PMID- 15560564
TI  - [A rare cause of upper digestive tract bleeding--pancreatic papillary
      adenocarcinoma].
AB  - Authors present a rare case of upper digestive bleeding, the etiology of which is
      represented by a pancreatic papillary adenocarcinoma placed in the body and tail
      of the pancreas, with bleeding through the Oddi's sphincter, which causes
      difficult problems of medical and surgical diagnosis and treatment. The patient
      was known with acute cholecysto-pancreatitis of lithiasic cause, which has been
      surgically cured in 1977, being under treatment in the last years for the
      pancreatic injury which had been chronic pancreatitis and for hyperglycemia. The
      laboratory explorations emphasized a severe anaemia which was identified through
      upper digestive endoscopy (intermittent active bleeding from the major papilla)
      confirmed by echo and CT exam (heterogeneously body tissue of 10/8 cm diameter,
      involving the body and the tail of the pancreas). The medical treatment was
      complex, including proteic, hematologic, acido-basic, balance of hyperglycemia,
      and was followed by the surgical intervention consisting in body and tail
      pancreatico-splenectomy, followed by a postsurgical abscess, which required
      drainage. The surgical evolution was favorable. 6 months after leaving the
      hospital, the patient was admitted to medical diseases clinic with the diagnosis
      of deep right ileofemoral thrombophlebitis, duodenal acute ulcer and acute
      pneumonia of average right lobe, causing difficult problems of medical treatment.
      On this pathologic background, the diabetic failure also appears and the echo
      exam showing multiple secondary hepatic and peritoneal metastatic determinations.
      In medical literature we only met 13 similar communications, problems of
      diagnosis and treatment being very much alike to those presented.

PMID- 15560565
TI  - Inflammatory pseudotumor of the spleen.
AB  - We report a case of a patient with inflammatory pseudotumor (IPT) of the spleen.
      IPTs can appear at many sites and represent rear lesions of uncertain
      etiopathogenesis. Usually they present as mass lesions, so the clinical and
      radiologic features often suggest malignancy. However, the microscopic findings
      are quite characteristic, and the diagnosis can be made readily by identifying
      the reactive nature of the cells. Diagnostic problems can arise when these
      lesions occur in lymphoid organs or the spleen.

PMID- 15560566
TI  - [Percutaneous endoscopic cholangioscopy (percutaneous cholangioscopy)].
AB  - The aim of this paper is to present the percutaneous cholangioscopic method,
      objectives, indications, technique and advantages of this method in exploration
      and treatment of common bile duct disease. Percutaneous cholangioscopy is a
      complementary mini-invasive method, which is associated to classic or
      laparoscopic surgical procedures on common bile duct disorder. This method has
      the main characteristic intraductal approach, which is made via an external
      preformed fistula derived from an anterior surgical open or mini-invasive
      interventional procedures performed on the common bile duct. Percutaneous
      cholangioscopy is very performing in early or differential diagnosis
      determination of common bile duct malignant tumors and is a valuable method for
      mini-invasive intraductal treatment that can be performed by this method,
      avoiding another interventional surgical or endoscopical procedure on common bile
      duct.

PMID- 15560567
TI  - Applying mode-of-action and pharmacokinetic considerations in contemporary cancer
      risk assessments: an example with trichloroethylene.
AB  - The guidelines for carcinogen risk assessment recently proposed by the U.S.
      Environmental Protection Agency (U.S. EPA) provide an increased opportunity for
      the consideration of pharmacokinetic and mechanistic data in the risk assessment
      process. However, the greater flexibility of the new guidelines can also make
      their actual implementation for a particular chemical highly problematic. To
      illuminate the process of performing a cancer risk assessment under the new
      guidelines, the rationale for a state-of-the-science risk assessment for
      trichloroethylene (TCE) is presented. For TCE, there is evidence of increased
      cell proliferation due to receptor interaction or cytotoxicity in every instance
      in which tumors are observed, and most tumors represent an increase in the
      incidence of a commonly observed, species-specific lesion. A physiologically
      based pharmacokinetic (PBPK) model was applied to estimate target tissue doses
      for the three principal animal tumors associated with TCE exposure: liver, lung,
      and kidney. The lowest points of departure (lower bound estimates of the exposure
      associated with 10% tumor incidence) for lifetime human exposure to TCE were
      obtained for mouse liver tumors, assuming a mode of action primarily involving
      the mitogenicity of the metabolite trichloroacetic acid (TCA). The associated
      linear unit risk estimates for mouse liver tumors are 1.5 x 10(-6) for lifetime
      exposure to 1 microg TCE per cubic meter in air and 0.4 x 10(-6) for lifetime
      exposure to 1 microg TCE per liter in drinking water. However, these risk
      estimates ignore the evidence that the human is likely to be much less responsive
      than the mouse to the carcinogenic effects of TCA in the liver and that the
      carcinogenic effects of TCE are unlikely to occur at low environmental exposures.
      Based on consideration of the most plausible carcinogenic modes of action of TCE,
      a margin-of-exposure (MOE) approach would appear to be more appropriate. Applying
      an MOE of 1000, environmental exposures below 66 microg TCE per cubic meter in
      air and 265 microg TCE per liter in drinking water are considered unlikely to
      present a carcinogenic hazard to human health.

PMID- 15560568
TI  - Toxicity of dipyridyl compounds and related compounds.
AB  - Five dipyridyl isomers, 2,2'-, 2,3'-, 2,4'-, 3,3'-, and 4,4'-dipyridyl, are
      products resulting from the pyrolytic degradation of tobacco products and
      degradation of the herbicide paraquat, and therefore may be present in the
      environment. In this article, the toxicological properties of these dipyridyl
      isomers in humans and animals are reviewed. Epidemiological studies suggest that
      cancerous skin lesions in workers involved in the manufacturing of paraquat may
      be associated with exposure to dipyridyl compounds. Experimental animal studies
      suggest that dipyridyl isomers may have several toxicological effects. Three of
      the dipyridyl isomers (the 2,2', 2,4', and 4,4' isomers) appear to be inducers of
      some metabolic enzymes. The 2,2'-dipyridyl isomer, an iron chelator, appears to
      influence vasospasm in primate models of stroke. The cytotoxic effects of 2,2'
      dipyridyl on several leukemia cell lines have been reported, and a potent
      teratogenic effect of 2,2'-dipyridyl has been observed in rats. Based on the
      results of paraquat studies in experimental animal models, it has been proposed
      that paraquat may have deleterious effects on dopaminergic neurons. These
      findings support the epidemiological evidence that paraquat exposure may be
      associated with the development of Parkinson's disease. Studies designed to
      determine an association between paraquat exposure and Parkinson's disease are
      complicated by the possibility that metabolic changes may influence the
      neurotoxicity of paraquat and/or its metabolites. Preliminary unpublished data in
      mice show that 300-mg/kg doses of 2,2'-dipyridyl are neurotoxic, and 300-mg/kg
      doses of 2,4'- and 4,4'-dipyridyls are lethal. These results are consistent with
      earlier studies in Sherman rats using high 2,2'- and 4,4'-dipyridyl doses. New
      studies are needed to further explore the toxicological properties of dipyridyls
      and their potential public health impact.

PMID- 15560569
TI  - [The experience of diagnostic and surgical treatment of Barrett's oesophagus].
AB  - There were analyzed five-year late results of prospective investigation on
      surgical treatment of 23 patients, suffering long-segment Barrett's esophagus
      (BE). Esophagoplasty and esophagocardioplasty was performed in 7 (30.4%) patients
      and total fundoplication in combination with endoscopic ablation of metaplastic
      epithelium--in 16 (69.6%). Excellent and good results marks in 19 (827%) of
      patients, including those with antireflux operation, and satisfactory--in 4
      (17.3%), witnessing high efficacy of surgical treatment in the BE correction.

PMID- 15560570
TI  - [Lipid peroxidation in patients with multiple peptic ulcers in the stomach and
      duodenum].
AB  - Under the observation there were 62 patients with multiple ulcers of a stomach
      and duodenum from 23 till 65 years old, randomized under the sex, age and
      character of pathological process (sizes and localization of peptical ulcers). In
      all patients the parameters of lipids peroxidation were studied. The increase of
      intensity the peroxidation of lipids were revealed, at the expense of
      augmentation in a peripheric blood of the patients of concentration of a final
      metabolite peroxidation of lipids--malon's dialdehyde and intermediate products-
      dien's conjugates. The rising of a parameter hemolysis peroxidation of
      erythrocytes is marked also.

PMID- 15560571
TI  - [Biochemical markers in diagnosis and prognosis of obturative jaundice].
AB  - The results of complex examination and treatment of 175 patients with obturative
      jaundice of different genesis were analyzed Especial attention have been devoted
      to interaction of specific enzymes: aminotransferases, alkali phosphatase and
      gamma-glutamiletranspeptidase. It was established some connection of the activity
      of these enzymes in obturative jaundice and liver functionally-morphologic state.
      This had been confirmed by facts of laboratory investigations date. Comparison of
      these indexes will promote the increase of diagnostic informativity, that can be
      used as one of diagnostic and prognostic criterions.

PMID- 15560572
TI  - [Drainage operation for the infectious pancreonecrosis].
AB  - The prospective investigation a was conduct in 218 patients and retrospective
      ones--in 253 patients. The results of drainage operations in infectious forms of
      pancreonecrosis were studied basic task in preoperative period was adequate
      antibacterial therapy, directed on all microorganisms.

PMID- 15560573
TI  - [The role of enteropathogenic infection, local immunity, and autosensibilisation
      in pathogenesis of acute surgical diseases of peritoneal cavity by the example of
      acute appendicitis].
AB  - The complex of interrelated pathogenic factors in development of postoperative
      suppurative inflammatory complication with abdominal cavity organs lesion was
      studied on the example of an acute appendicitis. It includes enteropathogenic
      microorganisms, insufficiency of local immunity, deficiency of immunoglobulins,
      lysozym. Findings show the possibility in seeking the measures of prevention of
      emergent state, in particular, an acute appendicitis.

PMID- 15560574
TI  - [Pelvic imaging modified by rectum predefecatory distension].
AB  - Computed tomography (CT) rectum imaging limited by anatomy, pathological process
      and CT own characteristics. The ways of image improving are: endorectal scanning,
      myorelaxatives, contrast substances. Rectum and anal canal has oval serrated
      profile without distension on CT and US scans. Purpose is to improve the CT and
      endorectal US scan role in pelvic structure changing disorders operating plan
      estimating.

PMID- 15560575
TI  - [Choice of surgical tactics in patients with multiple trauma and predominant
      injury of hollow abdominal organs, diaphragm, and pancreas].
AB  - The experience of treatment of 67 suffered with predominant injury of hollow
      abdominal organs, diaphragm and pancreas is present. The choice of surgical
      tactics was depend of many factors: time from accident to operation, the severity
      stage of patients, presence of extraabdominal injuries, localization and degree
      of abdominal organ injuries.

PMID- 15560576
TI  - [The volume of surgery on the abdominal cavity organs in patients with associated
      cardiovascular and respiratory system diseases].
AB  - The cardiovascular and respiratory disturbances are the main risk factor in acute
      and chronic surgical deseases of the abdominal cavity organs, including
      oncological. It is limits the possibility and volume of the diagnostics and
      surgical tactics choice. The complicated current of main disease is a risk factor
      of operation perform and the reason of the undertaking inadequate and palliative
      intervention, which significant reduce of the quality of life. Real by risk level
      reductions in surgery is a determination of tissues viability, estimation of
      compensatory reserve sick evidences for determination for operation performance
      including simultaneous and staged.

PMID- 15560577
TI  - [Problems of hemotransfusion from the evidence-based medicine point of view].
AB  - The operational analysis of hospital is conducted on blood transfusion for 5
      years. For this time the main parameters of activity were improved and the
      quantity of blood transfusions has decreased The parameters of activity have not
      worsened. The number of AIDS--carriers was considerably increased, high there is
      still the level of a morbidity by hepatitis B and hepatitis C. Presently blood
      transfusion is equated to transplantation of an organs. From the attitude of
      evidential medicine it is necessary to prune the number of blood transfusions.
      The complications of a blood transfusion have been analyzed. The alternate
      methods of treatment are induced.

PMID- 15560578
TI  - [Surgical tactic in the injury of neck vessels].
AB  - Retrospective analysis of the surgical treatment results in 50 injured persons
      with the damage of the neck vessels in 1998-2003 yrs period was presented.
      Restorational-reconstructive operations were performed in 19 (38%) injured
      persons with the arteries damage, in 10 (20%)--with the veins damage, the
      ligature operations were done, accordingly, in 6 (12%) and in 20 (40%).
      Satisfactory result was noted in 41 (82%) injured persons. Neurological
      complications had occurred in 4 (8%) of patients. Mortality had constituted 10%
      (5 patients died). The principles of surgical treatment of the neck vessels
      damage were stated.

PMID- 15560579
TI  - [Surgical treatment of chronic post-thromboembolic pulmonary hypertension].
AB  - Results of surgical treatment of 9 patients with postembolic chronic pulmonary
      hypertension, to whom thrombendarterectomy of the pulmonary artery branches was
      performed, using artificial blood circulation method, were studied up.
      Indications for conduction of operative treatment, including the heart--lungs
      complex transplantation, were made more precise. The ways of improvement of the
      surgical treatment results in patients, suffering this complication, were
      outlined.

PMID- 15560580
TI  - [Modern tendencies of malignant pleural effusions epidemiology].
AB  - The during 7 years 258 patients with malignant effusion (ME) of different
      ethiology were treated in clinic, that composed 13.8% among all patients with
      pleural effusion. It was discovered the increase of this complication frequence
      in 1.6 time. The main reasons of ME were lung cancer--in 42.6% of observations,
      pleural mezothelioma--in 19.3%, mammary glands cancer--in 6.9%, real reason of ME
      was not found in 13.9%. Aged patients (oldest 60 years) are risk group for
      discovering of ME, for pleural mezothelioma the next ages are risk 30-40 and
      oldest 60 years.

PMID- 15560581
TI  - [Effect of anticoagulants on remote results after surgical treatment of patients
      with colon cancer depending on tumor growth and differentiation].
AB  - The long-term results of radical surgical treatment of the patients with colon
      cancer are shown at usage in the postoperative period calcium nadroparin,
      ticlopidine and unfractionated heparin. At the comparative analysis is
      established, that at application calcium nadroparin, and calcium nadroparin in a
      complex with ticlopidine the increase of an index of a hollow--charge survival
      rate for a miscellaneous degree is marked, depending on a level of
      differentiation and growth form of a swelling.

PMID- 15560582
TI  - [Method of the tissue expanding in surgical treatment of the upper extremity
      deformity].
AB  - Results of surgical treatment of 14 patients suffering the segments deformity and
      the joints contracture of the upper extremity, using the tissue expanding method,
      were analyzed. The latex expanders as well as those, made according to own model
      were applied for the dermotension commitment. The peculiarities and modes of
      operation of the upper extremity tissues expanding were determined. Application
      of the tissues balloon expanding method during elimination of the upper
      extremities deformity and the joints contracture had permitted to achieve in
      immediate period the positive functional and cosmetic results in 83% of
      observations. In the late period good results were noted in 75% of patients and
      satisfactory--in 25%.

PMID- 15560583
TI  - [Experimental substantiation of the method of biological tissue welding in
      surgical hepatology].
AB  - Application of the welding method for biological tissues in hepatobiliary surgery
      was experimentally substantiated. In 14 pigs (25-30 kg body mass) resection of
      one hepatic lobe, using electric welding method, was done. In control group (4
      pigs) the similar operative intervention was accomplished, using conventional
      method. Application of the electric welding method guarantees secure hemostasis
      and cholestasis, do not causes specific pathological changes in the adjacent
      region of affection tissues, speed of restoration of the structures damaged
      exceeds such in application of the suturing method.

PMID- 15560584
TI  - [The method of surgical treatment of perforative pyloroduodenal ulcer].

PMID- 15560585
TI  - [Peptic ulcer of artificial esophagus].

PMID- 15560586
TI  - [The diaphragm injury with the diaphragmal hernia formation].

PMID- 15560587
TI  - [Rare complication after the catheterisation of subclavian vien in child].

PMID- 15560588
TI  - [The application efficacy of immunomodulators in complex of treatment of an acute
      necrotic pancreatitis].
AB  - Analysis of efficacy of the immunomodulators application, thymalin in particular,
      in complex treatment algorhythm in 18 patients with an acute necrotic
      pancreatitis was conducted. Efficacy of immunocorrecting therapy in the immune
      state improvement, purulent-septic complications prophylaxis, the abortive course
      of the disease promotion was established In 12 (66.7) patients the disease
      regression was noted, in 2 (11.1%)--the inflammatory process delineation with
      pancreatic pseudocyst formation was observed, 4 (22.2%) patients were operated
      on. All the patients survived.

PMID- 15560589
TI  - [Change of the cell immunity indexes in patients with multiple gastroduodenal
      ulcers under the influence of surgical treatment].
AB  - There were followed up 62 patients with multiple gastroduodenal ulcers. Before
      the operation in them distinct changes of the cell chain of immunity were
      established: T-lymphopenia, the T-lymphocytes subpopulations dysbalance,
      predominantly with reduction of the circulating T-helpers/inductors (CD4+)
      quantity with preservation on nearly normal and moderately subnormal level of T
      suppressors/killers (CD8+), the immunoregulatory index (CD4/CD8) lowering. The
      quantity of B-lymphocytes (CD22+) was in normal limits or moderately reduced.
      Essential lowering of index of the lymphocytes blasttransformation reaction was
      noted, witnessing inhibition of the T-lymphocytes functional activity occurrence.
      Overall the data obtained have had witnessed the secondary immunodeficiency state
      presence, which deepened after operative intervention performance and was not
      removed as a result of the conventional treatment conduction.

PMID- 15560590
TI  - [Application of meloxicam in scheme of prophylaxis of postoperative complications
      in patients with an acute ileus of tumoral etiology].
AB  - Meloxicam application in complex of prophylactic treatment of patients with
      colonic cancer, complicated by an acute obturation ileus, had promoted the
      lowering of postoperative complications rate, caused by inhibition of the
      inflammation mediators synthesis and connected with him pathologic reactions of
      the systemic inflammatory response syndrome (SIRS).

PMID- 15560591
TI  - [New technology of the operative wound suturing as the purulent-inflammatory
      complications prophylaxis in urgent surgical abdominal diseases].
AB  - New technology of the operative wound suturing was elaborated with performance of
      muscle-aponeurotic suture in 115 patients, operated on for emergent diseases,
      securing lowering of postoperative compications rate from 2.43 to 1.73%.

PMID- 15560592
TI  - [Relaparotomy as effective method of treatment for injured persons with closed
      abdominal trauma complications].
AB  - The retrospective analysis of treatment of 42 patients with the closed abdominal
      trauma, whom the relaparotomy carried out. Principal causes bringing to repeatcd
      operative interventions were separated, and classification of operations
      depending on terms of performance, are allocated. An inclination the basic
      directions as system and local character are allocated.

PMID- 15560593
TI  - [Application of the Decasan at the practice of urgent surgery].
AB  - The results of complex treatment of 37 patients operated on for the various acute
      abdominal surgical diseases were presented. Among them 22 patients for locally
      treated 0.02% antiseptical solution Decametoxin were used. Positively impact
      clinical course of the diseases reducing their purulent and septic morbidity rate
      in particular were evidenced separately in the patients operated on for acute
      necrotic pancreatitis.

PMID- 15560594
TI  - [The risk factors in operative treatment of an acute and chronic surgical
      diseases].
AB  - According to retrospective analysis of the surgical treatment of patients in
      presence of cardial risk factors it was established the absence of alternative
      for surgical intervention while choosing the treatment tactic in 80% of
      observations, in 16%--the necessity for relaparotomy performance. The direct
      cause of death in this patients was cardial insufficiency and coronary blood
      circulation insufficiency, and complications of principal abdominal surgical
      disease. To improve the results of treatment of this severely ill patients it is
      expedient to conduct one-stage and the staged surgical and cardiosurgical
      intervention.

PMID- 15560595
TI  - [Classification of malignant tumors of suprarenal glands].
AB  - The extent of diagnostic possibilities of medical technique, permitting to reveal
      the majority of suprarenal tumors, and the most modem information technologies as
      well demands creation of the suprarenal tumors applicable classification, well
      adopted for physician in practice and also for scientist dealing with analysis of
      the investigation results in these pathology. Taking into account hormonal
      activity of majority of tumors, influencing the patients management tactic, the
      authors propose the insight on suprarenal tumor diagnosis of their own.

PMID- 15560596
TI  - [Application of plasmapheresis in complex of preoperative preparation in patients
      with autoimmune thyroiditis and diffuse toxic goiter].
AB  - The article is devoted to actulal problem of endocrinology and surgery-treatment
      of severe diseases of the thyroid gland. Results of plasmapheresis application in
      complex preoperative preparation in 90 patients, aged from 20 to 60 yrs, in
      severe course of the disease, were adduced. After plasmapheresis preparation
      conduction the reduction of the autoimmune processes in the patients organisms,
      the antibodies titer lowering were noted, witnessing the stable remission
      achievement. Plasmapheresis application in complex of treatment of patients with
      autoimmune thyroiditis and diffuse toxic goiter causes significant positive
      influence on hormonal and immune state.

PMID- 15560597
TI  - [Experience of the complications treatment after operative intervention for the
      thyroid gland cancer].
AB  - In 1998-2003 yrs in the clinic there were treated 360 patients with the thyroid
      gland diseases, 147 (40.8%) of them were operated. In 19 (12.9%) of patients
      various kinds of complications had occurred.

PMID- 15560598
TI  - [Surgical treatment of injured persons with the main blood vessels damage].
AB  - Retrospective analysis of the surgical treatment results of 45 injured persons
      with damage of main blood vessels was presented. Specific operative methods in
      injury of the different type main blood vessels, localized in thoracic and
      abdominal cavities, were depicted. In 35 (77.8%) injured persons good and fair
      results of restoration operations were noted. The lethality rate was 22.2%. The
      tactic of surgical treatment of the main blood vessels injury was presented.

PMID- 15560599
TI  - [Treatment of arterial hypoxemia in early period of traumatic disease].
AB  - Issues of arterial hypoxemia treatment in early period of traumatic disease,
      taking into account modern approaches, adopted in surgery of injuries and
      anesthesy-resuscitation. It is recommended to use the method proposed for the
      arterial oxygen content enhancing in an acute respiratory insufficiency of
      various genesis, including the cases of progressive posttraumatic disease.

PMID- 15560600
TI  - [Surgical classification of the diabetic foot syndrome].
AB  - Surgical classification of the diabetic foot syndrome was proposed, permitting to
      formulate pathogenetic diagnosis with working out in detail the foot pathologic
      process depth and expansion, taking into account the microflora presence in the
      purulent-necrotic affection zone, basing on own experience of treatment of 490
      patients. This permits to formulate tactic and volume of necessary pathogenetic
      surgical and conservative treatment.

PMID- 15560601
TI  - [Differential diagnosis of Raynaud's phenomenon--modern state of the problem].
AB  - Results of examination of 108 patients with the Raynaud's phenomenon were
      analyzed. The differential diagnosis algorhythm for the disease and the syndrome
      as well was elaborated. The leading role of the clinical features and the data of
      the physical examination methods in the diagnosis establishing was proved.
      Diagnostic complex for the functional state investigation of the upper extremity
      microvascular bed was elaborated.

PMID- 15560602
TI  - [Surgical treatment of spontaneous and traumatic pneumothorax].
AB  - The ten-year experience of the regional hospital thoracic department in treatment
      of 723 patients with spontaneous pneumothorax and 678 injured persons, suffering
      complicated thoracic trauma, was summarizd. The tactic and methods of treatment
      of such patients, using modern technologies and endoscopic operations, was
      depicted. Comparative analysis of the different methods efficacy, their results,
      advantages and faults estimation were conducted. Recommendations for application
      of every method of treatment in various clinical situations were adduced.

PMID- 15560603
TI  - [Apparatuses for the wound closure in modern surgical practice].
AB  - The method of the wounds treatment, using apparatuses for their edges
      rapprochement, was elaborated, basing on analysis of clinico-experimental
      investigations conducted. The method was successfully applied for the wounds
      closure after excision of coccygeal channel, the soft tissues abscess and
      phlegmon, postoperative ligature fistula and in temporary closure of laparotomy
      wound in patients with purulent peritonitis.

PMID- 15560604
TI  - [About the necessity of the state policy in editing of the medical text-books in
      conditions of the higher education rebuilding (after the example of the general
      surgery course)].

PMID- 15560605
TI  - [Observation of pulmonary artery fibrosarcoma with clinical signs of pulmonary
      thromboembolism].

PMID- 15560606
TI  - [Intestinal iersiniosis in practice of a surgeon].

PMID- 15560607
TI  - [Modified of Deshane's ligature needle].

PMID- 15560608
TI  - [Observation of esophageal polyp, protruding in oral cavity].

PMID- 15560609
TI  - [Periampullary villous duodenal polyp].

PMID- 15560610
TI  - [Traumatic rupture of rectum with the small intestine anal prolapse].

PMID- 15560611
TI  - [The change or correction of mitral valve in combination with the aortal valve
      change].

PMID- 15560612
TI  - [Surgical treatment of giant intrathoracic goiter].

PMID- 15560613
TI  - Your country needs you ... to vote!

PMID- 15560614
TI  - Helping prevent violence against pregnant women.

PMID- 15560615
TI  - Preventing hypertension. More Americans than ever before have prehypertension or
      high blood pressure.

PMID- 15560616
TI  - Depo Provera increases risk for chlamydial, gonococcal infections.

PMID- 15560617
TI  - Genetic discrimination. Individual protection legislation stalls in Congress.

PMID- 15560618
TI  - Preventing infant death and injury during delivery.

PMID- 15560619
TI  - Update on cholesterol guidelines: more intensive treatment options for higher
      risk patients.

PMID- 15560620
TI  - Can periodontal disease lead to premature delivery? How the mouth affects the
      body.

PMID- 15560621
TI  - Lifelines patient page. How oral care affects your baby's health.

PMID- 15560622
TI  - Operating a comprehensive high-risk breast cancer management program in a
      community hospital setting.

PMID- 15560623
TI  - Obstetric triage & EMTALA regulations. Practice strategies for labor and delivery
      nursing units.

PMID- 15560624
TI  - Improving patient care and safety. Exploring the perinatal risk assessment
      process.

PMID- 15560625
TI  - Days of waiting. Bedrest with a twin pregnancy.

PMID- 15560626
TI  - A bigger piece of the pie. For-profit facilities climb to 16% of all community
      hospitals, as not-for-profits struggle with access to capital, rural challenges.
AB  - The percentage of investor-owned hospitals is at an all-time high, helped in part
      by sales of not-for-profit facilities. Hillcrest HealthCare System's board
      decided to sell 10 of its hospitals after taking a hard look at its finances. "We
      weren't concerned about the short term, but the long term," Don Lorack, left,
      said.

PMID- 15560627
TI  - Another shot at reform. Washington has hope after Calif. defeats Prop. 72.

PMID- 15560628
TI  - Election 2004. The prognosis is a bit mixed.

PMID- 15560629
TI  - Feeling the heat. State hospital associations settle with IRS.

PMID- 15560630
TI  - CMS rejiggers outlier rules.

PMID- 15560631
TI  - Making the leap. When hospitals look to insurers for executive talent.

PMID- 15560632
TI  - Welcome to the club. IOM reports on quality improvement of rural care.

PMID- 15560633
TI  - Quality. Better, but not good enough.

PMID- 15560634
TI  - Done deal. Vista Health to consolidate services, close facility.

PMID- 15560635
TI  - Hospitals. Weighing need against want.

PMID- 15560636
TI  - Responding to an antitrust investigation. When the FTC calls, be sure to get an
      experienced lawyer, cooperate fully and don't be afraid to settle.

PMID- 15560637
TI  - Prescribing a pharmacy benefits manager. The shadowlands of PBMs. Seek out the
      experts to navigate the gray territory of drug-benefits managing.

PMID- 15560638
TI  - Certifying insurance eligibility. Show them the money. Requiring payment upfront
      protects hospitals from getting stuck with the bill.

PMID- 15560639
TI  - Billing the uninsured. Surviving a no-win situation. CMS, HHS offer guidelines,
      direction on how to bill uninsured patients.

PMID- 15560640
TI  - Increasing your Medicaid match. Too much of a good thing? Fine line between
      improving reimbursement and taking advantage of the system.

PMID- 15560641
TI  - Testifying before Congress. The hot seat. When making your case, it's important
      to know the purpose of the hearing.

PMID- 15560642
TI  - Getting hired as a CEO after 50. Making age an asset. Years of experience,
      combined with enthusiasm, can be a winning combination.

PMID- 15560643
TI  - Surviving a no-confidence vote. Communication is key. Keeping everyone informed
      can help an executive win over employees.

PMID- 15560644
TI  - Selling a medical office building. A valuable commodity. Medical office buildings
      offer hospital systems an additional form of revenue.

PMID- 15560645
TI  - Buying a not-for-profit hospital. Slow and steady wins the race. Complementary
      missions can lead to matches made in healthcare heaven.

PMID- 15560646
TI  - Still a priority. Health system needs didn't go away on election day.

PMID- 15560647
TI  - From patients to policies. Why do physicians think they can make the jump from
      running practices to running multibillion-dollar insurance companies?

PMID- 15560648
TI  - First do no harm: get your flu shot!

PMID- 15560649
TI  - Drug diverting patients & prescription monitoring--both sides of the debate.

PMID- 15560650
TI  - Professional liability discussions, Medicaid and elections rule the day.

PMID- 15560651
TI  - Working to fix Medicaid for Iowa.

PMID- 15560652
TI  - Retire? Now? Are you kidding me?

PMID- 15560653
TI  - Vaccinating health care workers for influenza--a real patient safety issue.

PMID- 15560654
TI  - [Should children with familial hypercholesterolemia be treated with statins?].

PMID- 15560655
TI  - ["Sprained ankle" gives emergency room physicians headache. The Ottawa method
      gives guidelines for x-ray examination].

PMID- 15560656
TI  - [ECMO treatment saved life of a young woman with acute pulmonary embolism].
AB  - A 42-year old obese female using contraceptive medication was admitted to the
      emergency room because of sudden onset of dyspnoea and hypoxia. Computed
      tomography showed massive pulmonary emboli. Despite initial treatment with
      thrombolysis her condition deteriorated further and she was referred for acute
      surgery to our clinic. Before putting the patient to sleep extracorporeal
      circulation was instituted with access from the groin. After anaesthesia a median
      sternotomy was performed. With the heart beating, the main pulmonary artery was
      incised and a 9 cm long thrombus was removed. Immediate weaning from the heart
      lung machine was not possible, mainly because of bleeding to the airways. The
      right atrium and the aorta was therefore cannulated and an extracorporeal
      circulation membrane oxygenator (ECMO) was used for three days. The patient
      required several re-entries for bleeding and a tracheotomy during the
      postoperative course. She was fully recovered three months after the operation.

PMID- 15560657
TI  - [Surgery in acute pulmonary embolism can be a life-saving therapeutic
      alternative. A follow up of surgically treated patients].
AB  - Acute pulmonary embolism occurs in about 10,000 people annually in Sweden, in
      more than 1000 of whom it has a fatal outcome. The clinical presentation may vary
      considerably, and a large number of patients with pulmonary embolism are still
      misdiagnosed. Most patients are treated with anticoagulants and some also with
      thrombolysis. During a 40-year period, 1957-1996, 12 patients underwent emergency
      pulmonary embolectomy at the Karolinska Hospital in Stockholm, Sweden. Of these,
      two (17%) died from anoxic brain damage within the first postoperative month.
      Four patients died 15-21 years after surgery. Six patients who were still alive
      at follow-up in 2003 were contacted 7-36 years after the embolectomy and were all
      in good health. In none of them had pulmonary embolism recurred, but two had
      suffered deep venous thrombosis. We conclude that emergency pulmonary embolectomy
      can be a lifesaving procedure, with a good long-term prognosis in patients who
      survive the early perioperative period.

PMID- 15560658
TI  - [Observation for the assessment of acute chest pain is required. Analysis of case
      published in Annals of Internal Medicine and measures relevant for Swedish
      conditions].

PMID- 15560659
TI  - [Alarming tendency of increased number of dropouts in epidemiologic case-control
      studies].

PMID- 15560660
TI  - [Role of medical journals in the shaping of medical knowledge].

PMID- 15560661
TI  - [Care of the mentally disabled mirrors the existing society. Dramatic changes
      during the last decade].

PMID- 15560662
TI  - [The Swedish MS registry points out an important clinical problem: physical and
      psychological fatigue is a main symptom in multiple sclerosis].

PMID- 15560663
TI  - [Peer review of scientific manuscripts should be open and referees' bias should
      be accounted for].

PMID- 15560664
TI  - [Treatment of acute otitis media--our article does not conflict with the
      consensus statement].

PMID- 15560665
TI  - [Needle biopsy in cancer diagnosis--proposal for improved technique].

PMID- 15560666
TI  - [Nuclear energy as a carbon dioxide-free alternative is not mentioned by the
      Physicians against Environment, why?].

PMID- 15560667
TI  - The review process.

PMID- 15560668
TI  - Pulmonary rehabilitation: analysis of a clinical service.
AB  - BACKGROUND AND PURPOSE: There is significant research supporting the role of
      pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD).
      However, less is known about real-life clinical rehabilitation services. Data
      were analysed from a clinical pulmonary rehabilitation service provided in the
      UK, consisting of seven weeks' twice-weekly training and education. METHOD: A
      retrospective study. Baseline measures consisted of activity of daily living,
      mood state, spirometry, exercise tolerance using the Incremental Shuttle Walk
      Test (ISWT) and health status using the St George's Hospital Respiratory
      Questionnaire (SGRQ). Responders to pulmonary rehabilitation were defined as
      those with a mean reduction of four points on the SGRQ and a mean increase of 48
      metres on the ISWT. RESULTS: One hundred and eight patients entered the programme
      and 91 completed it. All outcomes showed statistically and clinically significant
      change after the rehabilitation programme. Responder analysis showed that 37% of
      patients achieved benefits for both the SGRQ and the ISWT. Twenty-eight per cent
      of patients were non-responders for both; 17% benefited for the SGRO only and 14%
      improved their exercise tolerance. Patients with restrictive disease (n = 11)
      showed large mean ISWT score of 98.2 m (Standard deviation (SD) 69.4 m) (p <
      0.01), as did patients with moderate COPD (n = 30), who scored a mean ISWT change
      of 77.3 m (SD 92.0 m) (p < 0.01) and a SGRQ score of -7.6 (SD 13.7) (p < 0.01),
      and those with mild COPD (n = 12), who scored a mean ISWT change of 62.5 m (SD
      87.4 m) (p < 0.01) and a mean SGRQ change of -3. 7 (SD 8.1) (p < 0.01). Patients
      with severe COPD (n = 23) showed a smaller mean change in ISWT of 32.6 m (SD 79.4
      m) and in SGRQ of -2.8 (SD 7.1). However, analysis of variance (ANOVA) showed no
      statistical differences between the groups (p = 0.13). CONCLUSIONS: Clinical
      pulmonary rehabilitation programmes are effective for most patients. However for
      patients with more severe impairment, maximal gains may be harder, or take
      longer, to achieve. Patients with restrictive disease appear to do well, although
      future trials will be needed to test this supposition.

PMID- 15560669
TI  - Making words count: the value of qualitative research.
AB  - In the current climate of evidence-based practice, physiotherapy is urged to
      prove its worth via rigorous scientific research. However, there are concerns
      that limited methodologies are used to explore complex therapeutic issues, and
      that the profession relies too heavily on quantitative research studies to
      provide its evidence base. Qualitative research methods are able to explore the
      complexity of human behaviour and generate deeper understanding of illness
      behaviours and therapeutic interactions. Nevertheless, there is still a sense of
      distrust of qualitative research, related to the challenge of evaluating both the
      quality and usefulness of findings derived through qualitative methods. This
      discussion paper explores these issues. It examines some of the most frequently
      used techniques aimed at ensuring quality and value in qualitative research, such
      as sampling, triangulation, multiple coding, respondent validation and the use of
      audit trails, as well as addressing reflexivity. Because of the pluralistic and
      interactive nature of qualitative inquiry, the criteria used to judge quality
      need to be appropriate to each piece of research and should provide evidence to
      help readers to evaluate the calibre of the study and its relevance to their own
      area of work.

PMID- 15560670
TI  - Cardiovascular profile of adult recipients of chest physiotherapy.

PMID- 15560671
TI  - Time course of 'pusher syndrome' under visual feedback treatment.

PMID- 15560672
TI  - Therapeutic ultrasound as a treatment for chronic sinusitis.

PMID- 15560673
TI  - An individual approach to stroke recovery.

PMID- 15560674
TI  - Evidence based medicine: can we afford it?

PMID- 15560675
TI  - Treatment of dyslipidemia in chronic kidney disease.
AB  - Dyslipidemia is a common feature of various renal diseases. This perturbed lipid
      metabolism results in accelerated atherosclerosis and increased cardiovascular
      morbidity and mortality. Treatment of dyslipidemia, in addition to normalization
      of blood pressure and reduction of proteinuria, could provide additional means to
      retard the progression of chronic renal insufficiency. Possible therapeutic
      approaches include mainly dietary and life-style modifications, selective use of
      some technical components of dialysis systems, and the judicious prescriptions of
      lipid-lowering drugs. Even with relatively normal lipid and lipoprotein profiles
      statin therapy seems to prevent atherogenesis acceleration. A wide range of
      therapeutic interventions, targeting the lipid abnormalities that may develop in
      chronic renal patients and end-stage renal disease (ESRD) are currently
      available, though still without convincing evidence based on long-term
      prospective studies which clearly demonstrate a significant reduction in
      cardiovascular morbidity and mortality of ESRD patients. However, extensive
      investigations, concerning the best long-term therapeutic strategy for this high
      risk population of patients, are still missing.

PMID- 15560676
TI  - Inhibition of the effect of high glucose on the expression of Smad in human
      peritoneal mesothelial cells.
AB  - OBJECTIVE: As high glucose (HG) concentration in peritoneal dialysis (PD)
      solution is thought to contribute to peritoneal fibrosis, and angiotensin II
      receptor blockers (ARBs) may have a key role in preventing fibrosis as they may
      inhibit the TGF-beta1-Smad pathway, the aims of this in vitro study were to
      investigate 1) if HG affects the expression of Smad in human peritoneal
      mesothelial cells (HPMCs) and 2) if ARB (losartan) can inhibit this effect
      METHODS: HPMCs, obtained from non-renal patients undergoing elective abdominal
      surgery, were stimulated by HG solutions with different concentrations (1.5%,
      2.5%, 4.25%) of dextrose and mannitol, and by solutions containing combination
      with dextrose and losartan. The supernatant was assayed for TGF- beta1 by ELISA
      and cells were collected for the analysis of Smad family by RT-PCR and Western
      Blot. RESULTS: 1) HG up-regulated the expression of Smad2 on both gene and
      protein levels, especially in 2.5% and 4.25% dextrose groups (P<0.05), and also
      stimulated the expression of Smad4 in 4.25% dextrose group. However, the
      expression of Smad3 was not affected. 2) High osmolality as such (using mannitol)
      did not affect the TGF-beta1-Smad signaling pathway. 3) Losartan inhibited the
      expression of Smad2 on the gene level but not on the protein level. 4) HG up
      regulated the level of TGF-beta1 with increasing dextrose concentration, while
      losartan partially inhibited this effect of HG on releasing of TGF-beta1.
      CONCLUSION: A high glucose solution up-regulated the expression of Smad2 and
      Smad4, suggesting that the TGF-beta1-Smad pathway could be involved in the
      fibrosis of the peritoneum during PD. As losartan inhibited the expression of
      Smad2 on the gene level and reduced the concentration of TGF-beta1 in our study,
      the results of this in vitro study suggest that the use of angiotensin II
      receptor blockers might represent a possible way to prevent and treat peritoneal
      fibrosis in PD patients. However, further studies in vivo are needed to confirm
      this hypothesis.

PMID- 15560677
TI  - The relationship between inflammatory markers, leptin and adiponectin in chronic
      hemodialysis patients.
AB  - Chronic inflammation is prevalent in dialysis patients. We investigated the
      relationship between inflammation and newly identified adipokines: leptin and
      adiponectin in this population. A total of 129 chronic hemodialysis patients were
      collected. Serum high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6),
      leptin and adiponectin levels were determined as well as other metabolic
      variables. Correlation studies and multiple regression analysis were performed
      among variables. Our results showed that hemodialysis patients had elevated
      levels of inflammatory markers, leptin and adiponectin. Diabetic subjects had
      higher serum CRP and lower albumin levels than non-diabetics. Serum CRP levels
      were positively correlated with IL-6 levels and negatively correlated with
      albumin levels. Serum leptin levels were directly related to CRP levels while
      adiponectin levels were inversely related to CRP levels. A significant negative
      correlation was observed between serum leptin and adiponectin levels. Serum IL-6
      levels were the single independent factor affecting CRP levels. Body mass index
      can predict both serum leptin and adiponectin levels. We conclude that
      hemodialysis patients are at an increased risk of chronic inflammation and
      diabetes patients are even more susceptible to this status. Both serum leptin and
      adiponectin levels are associated with inflammatory markers. As adipose tissue is
      the major secreting site of these adipokines, our results suggest that adipose
      tissue plays an important role in the pathogenesis of chronic inflammation in
      dialysis patients.

PMID- 15560678
TI  - Hepatitis E virus antibodies in hemodialysis patients: an epidemiological survey
      in central Greece.
AB  - Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B
      hepatitis. Transmission is mainly via the fecal-oral route but the possibility of
      an additional parenteric transmission has been raised. Patients undergoing
      chronic hemodialysis (HD) have an increased risk of exposure to blood transmitted
      agents. Previous studies concerning prevalence of antibodies to HEV (anti-HEV)
      among HD patients gave conflicting results. The aim of the study presented here
      was to determine the prevalence of anti-HEV among HD patients of a well-defined
      semi-rural region in central Greece (Thessalia region). All patients (n=351, 234
      males, mean age 60+/-14 years) who were being treated in the HD units of central
      Greece (n=5) during 2001 were tested for anti-HEV antibody. Two commercially
      available specific solid-phase enzyme-linked immunoassays were applied for anti
      HEV detection. Hepatitis B virus markers, antibodies to HCV, HIV and HTLV were
      also screened in all patients by commercially available assays. Serum
      aminotransferase (AST, ALT) levels were measured by spectrophotometry. 17 anti
      HEV-positive patients were found and prevalence was 4.8%, varying from 1.8 - 9.8%
      in the various HD units. Prevalence of HBsAg and anti-HCV was 5.7% (2.9 - 15%)
      and 23.6% (11.5 - 36.2%) respectively. The anti-HEV prevalence was increased
      compared to healthy blood donors in Greece (0.26%, p < 0.01). The highest
      prevalence of anti-HEV was seen at the HD unit of the General Hospital of
      Karditsa (9.8%). Risk factors for anti-HEV antibody were not identified: no
      association was found between anti-HEV positivity and age or sex, duration of HD,
      hepatitis B or C virus infection markers, previously elevated aminotransferase
      levels or history of transfusion. Our investigation of HEV infection in the
      cohort of HD patients in central Greece showed that the prevalence of anti-HEV
      was greater than in healthy blood donors. There was no association to blood borne
      infections (HBV, HCV). The high prevalence of anti-HEV we found in one HD unit
      was probably related to a local infection in the past. However, long-term
      prospective studies are needed in an attempt to identify whether intra-unit
      factors are also responsible for the increased prevalence of serologic markers of
      HEV infection among HD patients.

PMID- 15560679
TI  - Temporary vascular catheters for hemodialysis: a 3-year prospective study.
AB  - BACKGROUND: Temporary hemodialysis catheters are necessary in patients with
      uremia, but complications associated with these catheters represent one of the
      most important sources of morbidity among ESRD patients. There is no general
      agreement about the optimal venous access for insertion of a central venous
      catheter, while risk factors of catheter related complications have not been
      entirely elucidated. METHODS: One hundred and seven consecutive patients who
      required a temporary hemodialysis catheter were prospectively examined. RESULTS:
      Catheters were placed in 107 consecutive patients (66 right jugular (JC), 41
      right femoral (FC)) and maintained in situ for a cumulative total of 2101 days.
      Early complications (puncture site hemorrhage, hematoma formation, artery
      puncture) were infrequent, without clinical sequelae. The main late complication
      was catheter related bacteremia (CRB). There were 16 episodes of CRB (JC-10; FC
      6) and Staphylococcus aureus was the most frequently isolated cause of CRB. The
      mean catheter duration before the onset of CRB was 19.9 and 18.2 days for JC and
      FC, respectively. Duration of catheter use, and the number of hemodialyses
      significantly increased the risk for CRB. Actuarial survival for FC was
      significantly worse than for JC, while Cox proportional hazard models revealed
      that the femoral site, chronic renal failure and kidney transplantation increased
      the risk of catheter failure significantly. CONCLUSION: CRB was the most common
      late complication. Its frequency was similar in JC and FC. The main risk factors
      for development of CRB were duration of catheter use and the number of performed
      dialyses. Cumulative hazard of CRB was significantly magnified 3 weeks after
      insertion for both JC and FC, but actuarial survival with JC was significantly
      longer.

PMID- 15560680
TI  - Mechanical heart valve cavitation: valve specific parameters.
AB  - Several aspects of mechanical heart valve cavitation, in particular of "severe"
      vapor cavitation, have been investigated in order to describe the phenomenon of
      cavitation itself and to classify various mechanical heart valves with respect to
      their tendency to cavitation. Furthermore, following the results of the
      measurements, a model for determination of time-dependent physical properties and
      dynamics of cavitation bubbles, such as size, pressure and temperature was
      developed. In order to classify the cavitation tendency of mechanical valves, a
      pulsatile hydraulic-driven circularly mock loop was used. Besides measurements of
      the relevant hemodynamic parameters, the leaflet velocities of the valves were
      also determined. In addition, numerous high-resolution pressure measurements, in
      particular the pressure drops necessary for the initiation of cavitation (local
      atrial pressure drop), were performed. For the investigation of bubble dynamics,
      a second pulsatile electro-magnetically-driven tester was used. The influence of
      density, viscosity and temperature of the fluid on the onset of cavitation was
      investigated. Cavitation events were recorded with a digital high-speed video
      camera (up to 40,500 frames/sec) for all investigated heart valves and under
      different conditions. A critical local upstream pressure drop (located within the
      model atrium after valve closure) of 450 mmHg was found for all valves as well as
      a valve specific correlation between left ventricular pressure gradient and local
      upstream pressure drop. Also, a valve dependent correlation between left
      ventricular pressure gradient and the local upstream pressure drop was provided.
      Finally, valve specific parameters were found to predict the cavitation tendency
      for a specific heart valve. The implementation of a suitable theoretical model
      allowed conclusions on bubble physics. High pressures (up to 800 bar) and
      temperatures (up to 1,300 degrees C) at bubble collapse have been determined. The
      influence of fluid parameters such as density, viscosity and temperature on the
      onset of cavitation is negligible within physiological range. Critical regions
      for cavitation for all mechanical heart valves were detected. All mechanical
      heart valves investigated show cavitation under different conditions (dp/dt)
      associated with high pressures and temperatures at bubble collapse. Cavitation
      bubble occurrence depends on valve design and location.

PMID- 15560681
TI  - Morphological analysis of in vivo velocity field in the alteration of the
      vasomotor tone.
AB  - Vessel wall remodeling is involved in atherogenesis and in several important
      vascular diseases affecting mainly aged and prosthetic implanted patients. This
      adaptive response to pathological states in arterial hemodynamics strongly
      suggests that flow-derived stresses act as mechanical stimuli to the release of
      endothelium-derived vasoactive factors, leading to vascular alterations. As the
      correlation of intimal hyperplasia (IH) with blood flow alterations in arteries
      has been shown to be significant, and as it is well-known that clinical
      procedures carry a substantial risk of development of vascular disease, the
      relevance of local hemodynamics must be investigated to describe changes in
      compliance matching in prosthetic applications. The aim of our research is to
      investigate the use of principal components analysis, together with varimax
      rotation, in the individuation process of morphological characteristics of real
      time ultrasound in in vivo recordings of blood flow velocities, as provided by
      two different carotid perivascular manipulations. This would be of use in the
      clinical assessment of atherogenesis, hypertension, prosthetic replacement or
      more in general in all applications in which vascular tone may be impaired. Data
      recordings refer to previous animal experiments where the Moncada model was
      investigated by means of an ultrasound profilometer. The present study confirms
      the feasibility of the proposed analysis to follow vascular pathology evolution,
      distiguishing between an in progress and a static situation.

PMID- 15560682
TI  - Development of counterpulsation algorithm for a moving-actuator type pulsatile
      LVAD.
AB  - A pulsatile left ventricular assist device (LVAD) was used to support the aortic
      blood pumping function of an injured left ventricle, and as a result helped its
      recovery. It is important to observe a left ventricle's pumping status and to
      adjust the operating status of a LVAD to reduce the left ventricle's pumping load
      and thus to enhance its recovery. To observe the left ventricle's pumping status,
      an electrocardiogram (ECG) signal is generally used because it is a result of the
      natural heart's blood pumping function. In this paper, we describe the
      development of an ECG based counterpulsation control algorithm that prevents
      simultaneous aortic blood co-pumping by a left ventricle and a moving-actuator
      type pulsatile LVAD and as a result, reduces the natural heart's pumping load. In
      addition, to verify the algorithm's applicability for LVAD control we designed
      three ECG based automatic pump control algorithms that use a developed
      counterpulsation control algorithm. These algorithms control the operating status
      of a LVAD automatically and, at the same time, maintain a counterpulsing status.
      The results of in vitro experiments show that the counterpulsing effect between a
      left ventricle and a LVAD was successfully produced and that the newly designed
      automatic pump control algorithms met their own control purposes with a
      counterpulsing effect.

PMID- 15560683
TI  - Reverse remodeling by net cardioplasty in a model of dilated cardiomyopathy:
      results of an animal study.
AB  - AIM: End-stage heart failure is a growing clinical problem with only a few
      satisfactory therapeutical options. Dilated cardiomyopathy (DCM) is associated
      with a progressive decline in cardiac function. Our hypothesis was to arrest this
      worsening of cardiac function by mechanically containing the dilated heart with a
      special net. METHODS: In 16 pigs (50+/-7 kg) DCM congestive heart failure was
      initiated by rapid ventricular pacing (220 b/m). In series 1 (n=8) a polyester
      net was placed around both ventricles before pacing was induced, whereas in
      series 2 (n=8) ventricular wrapping was performed when DCM was established.
      RESULTS: Comparing hemodynamic data before re-operation of group 11-animals, the
      decrease of CO and dp/dt(max) was significantly lower in series 1 than in series
      2 compared to the baseline values before pacing (CO: series 1:-22.6+/-3.3%,
      series 2:-52.4+/-6.4%, p<0.05; dp/dt: series 1: +16.4+/-2.8%, series 2: -51.5+/
      5.9%, p<0.05). In series 2, after net implantation, we could furthermore show
      that deterioration of the animal stopped and hemodynamic data improved
      significantly in the following 2 weeks (CO: +62.9+/-10.5% and dp/dt +37.0+/
      6.8%). CONCLUSION: Ventricular containment with a polyester net seems to be a
      therapeutic option in cardiac insuffiency caused by ventricular dilation. This
      cardioplasty induced a reverse remodeling of the dilated hearts with a
      significant improvement in diastolic and systolic ventricular function.

PMID- 15560684
TI  - Home care artificial heart monitoring system via internet.
AB  - The availability of a remote management system, which provides both physiological
      related information about the patient and device-related information about the
      implanted device, would be helpful during in vivo experiments or clinical trials
      involving artificial heart implantation. In order to be able to monitor the
      course of the in vivo experiment continuously regardless of the patient's
      location, an internet-based remote monitoring system was developed, which can
      monitor physiological-related information such as pressure (AoP, LAP, RAP, PAP)
      and flow data, as well as device-related information such as current, direction
      and pump operating conditions. The home care artificial heart monitoring system
      which we developed consists of four main components, which are the transcutaneous
      information transmission system (TITS), local monitoring station (LMS), data
      server station (DSS), and client monitoring station (CMS). The device-related
      information and physiological-related information can be transmitted in real time
      from a patient in a remote non-clinical environment to the specialist situated in
      a clinic depending on the current capabilities and availability of the internet.
      The local monitoring station situated at the remote site is composed of a data
      acquisition and preprocessing unit connected to a computer via its RS-232 port,
      and which communicate using a Java-based client-server architecture. The remote
      monitoring system so developed was used during an in vivo experiment of the
      artificial heart implantation for 2 months and performed successfully according
      to design specifications.

PMID- 15560685
TI  - Trends and dynamics of changes in aortic pulse wave velocity over one-year
      observation period in patients treated with peritoneal dialysis.

PMID- 15560686
TI  - Cutaneous plasmacytoma in a hemodialysis patient.
AB  - BACKGROUND: Extramedullary plasma cell dyscrasias are rare. CASE REPORT: We
      report a case of a 56-year-old male Caucasian hemodialysis patient with cutaneous
      plasmacytoma. The diagnosis was made a few months after surgical removal of his
      renal graft due to chronic rejection. Investigations for the presence of an
      associated myeloma were negative. He underwent local radiotherapy with complete
      resolution of the skin lesion. CONCLUSIONS: Nephrologists should be aware that
      the frequency of post-transplant lymphoproliferative disorders is increasing in
      the dialysis population, especially in those previously or currently treated with
      immunosuppressive drugs.

PMID- 15560687
TI  - Prevalence of gestational diabetes mellitus (GDM) in women screened by glucose
      challenge test (GCT) at Maharaj Nakorn Chiang Mai Hospital.
AB  - OBJECTIVE: To assess the prevalence of GDM in GCT screened women at Maharaj
      Nakorn Chiang Mai Hospital. STUDY DESIGN: Retrospective descriptive study.
      SETTING: Department of Obstetric and Gynecology, Maharaj Nakorn Chiang Mai
      Hospital. MATERIAL AND METHOD: One thousand pregnant women who attended the
      antenatal care clinic and delivered at Maharaj Nakorn Chiang Mai Hospital from
      October 2001 to December 2002 were recruited into the study. Glucose challenge
      test (GCT), 50-g glucose oral load with 1-hr plasma glucose measurement, was
      performed in GDM high-risk pregnancies. If GCT was positive, oral glucose
      tolerance test (OGTT), 100-g glucose orally, was done to confirm the final
      diagnosis. All relevant data including demographic information, previous
      obstetric history, risk factors for GDM, GCT and OGTT results and pregnancy
      outcomes were collected for further statistical analysis. MAIN OUTCOME MEASURES:
      Prevalence of GDM in GCT screened women, obstetric complications and pregnancy
      outcomes. RESULTS: There were totally 1000 pregnancies enrolled into the study.
      Despite 451 pregnant women being eligible for GCT only 411 cases were tested with
      164 positive results. 29 cases of GDM were detected with the prevalence of 7.05%.
      (CI 95% = 0.048, 0.099). As a result, the sensitivity, specificity, positive
      predictive value, and negative predictive value of GCT were 100%, 64.66%, 17.68%
      and 0%, respectively. In the GDM group, the common indications for GCT screening
      were advanced maternal age (75.4%), familial diabetic history (22.1%) and
      glycosuria (6.8%). Furthermore, only I case of pregnancy-induced hypertension was
      found with cesarean section, preterm birth, LGA and SGA of 27. 6%, 10.3%, 3.45%
      and 13.79%, respectively. There were 2 cases of pregestational diabetes mellitus
      (PGD; 0.2%) with 40 high-risk pregnancies (4%) without screening. CONCLUSION: The
      selective GCT screening strategy was highly effective and revealed 7.05% of GDM
      prevalence. Its impact on obstetric complication and pregnancy outcome was
      inconclusive due to the small number of studied population. Careful history
      reviewing plays an important role in identifying GDM risk factor for GCT
      screening.

PMID- 15560688
TI  - Immediate complications of laparoscopic tubal sterilization: 11 years of
      experience.
AB  - OBJECTIVE: To evaluate the complications of laparoscopic tubal sterilization.
      METHOD: A retrospective study of laparoscopic tubal sterilization performed at
      Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai, Thailand was
      conducted. The details of the operation, including complications and operation
      time were collected from the operative and family planning registry. RESULTS:
      Between January 1987 and December 1997, 948 cases of laparoscopic tubal
      sterilization were performed as an outpatient setting. The combination of
      intravenous sedation and local anesthesia was employed in all cases. Minor intra
      operative complications were found in 4.6% of cases. The most frequent
      complications were meso-salphingeal and meso-ovarian bleeding. No serious
      complication was found in this study. The mean operation time was 19.3 minutes
      (range 5-75 minutes). CONCLUSION: The present study suggested that out-patient
      laparoscopic tubal sterilization under the combination of intravenous sedation
      and local anesthesia is a convenient and relatively safe procedure.

PMID- 15560689
TI  - Comparison of two different fixed doses of follitropin-beta in controlled ovarian
      hyperstimulation: A prospective randomized, double blind clinical trial.
AB  - A prospective randomized, double blind, single centre study was conducted to
      compare the efficacy, efficiency and clinical side effects of daily fixed dose
      regimen of either 100 IU or 200 IU of recombinant follicle stimulating
      hormone(rFSH) Follitropin beta in down-regulated women undergoing controlled
      ovarian hyperstimulation(COH) for either conventional in vitro fertilization(IVF)
      or intracytoplasmic sperm injection(ICSI). A total of sixty women were randomly
      allocated according to the criteria for the treatment by either 100 IU(n = 30) or
      200 IU (n = 30) of FSH. Although more cycle cancellations due to low response
      were observed in the 100 IU group (n = 9 vs n = 2), two cases of mild and
      moderate ovarian hyperstimulation syndrome were noted in the higher dose group.
      Subjects in the group treated with 200 IU appeared to yield more follicles > 17
      mm (4.4 vs 3.3, p = 0.05) and more oocytes compared to the group treated with 100
      IU (9.2 versus 6.0 oocytes, NS). The total dosage required to develop at least
      three follicles according to the protocol was significantly lower in the group
      treated with 100 IU (1203.33 versus 2106. 67, P < 0.0001). In conclusion, a fixed
      daily dose of 200 IU of rFSH Follitropin beta compared to a fixed daily dose of
      100 IU is more effective in terms of follicles > 17 mm development and the number
      of oocytes retrieved along with a lower cancellation rate, but less efficient as
      indicated by a higher total rFSH dose needed

PMID- 15560690
TI  - The efficacy of cholesterol-lowering action and side effects of garlic enteric
      coated tablets in man.
AB  - The present study aimed at investigating the cholesterol-lowering and side
      effects of garlic enteric coated tablets in comparison with placebo tablets. The
      study is a randomized double-blinded crossover design involving 116 volunteers.
      However, 16 of them did not complete the study. The remaining 100 volunteers were
      divided into two groups: 45 were in the trial group and the remaining 55 in the
      control group. The volunteers in the trial group were asked to take garlic
      tablets in the first three months, placebo in the second three months and
      discontinue all tablets in the last three months, while the volunteers in the
      control group started with three months of placebo followed by three months of
      garlic tablets and ended up with three months of tablets discontinuity. The
      results showed that there were no significant differences in the total serum
      cholesterol levels between the two groups at the end of three months or six
      months of the study. Side effects included headache, itching and complaints of
      garlic smell. No serious side effects relating to liver, kidney functions or
      hematologic side effects were detected

PMID- 15560691
TI  - Study of cisplatin-vinblastine plus amifostine in patients with locally advanced
      or metastatic non-small cell lung cancer.
AB  - OBJECTIVE: To determine whether pretreatment with amifostine would reduce the
      toxicity of cisplatin with no reduction in antitumor efficacy in patients with
      advanced non-small lung cancer PATIENTS AND METHOD: Patients with locally
      advanced or metastatic non-small cell lung cancer, aged less than 75 years, with
      an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 were enrolled
      in the study. Amifostine was administered at a dose of 740 mg/m2 before
      chemotherapy. Then cisplatin at 100 mg/m2 was administered on day 1 and
      vinblastine 5 mg/m2 given on days 1, 8 and 15 in a 28 day cycle. RESULTS: Forty
      one patients were enrolled Baseline characteristics included; a median age of 58
      years (range, 28-72); 23 males and 18 females; performance status of 0 (1
      patient), 1 (38 patients) and 2 (2 patients); stage IIIa (1 patient), stage IIIb
      (10 patients) and stage IV (30 patients). The predominant histology was
      adenocarcinoma (60.97%). A median of 4 cycles (range, 1-6) were administered
      Thirty six cases out of forty one patients were assessable for response. The
      response rate was 38%. All those responding gave partial response. The median
      survival time was 33 weeks. One and two years survival were 23.9% and 9%
      respectively. Grade 3/4 toxicity was primarily hematologic. Grade 3/4 leukopenia
      occurred in 12.4%. Grade 3/4 thrombocytopenia occurred in 1.2%. Anemia grade 3/4
      occurred in 7.5%. The observed grade 3/4 nonhematological toxicities were
      hypertension, hypocalcemia, nausea and vomiting and sensory neuropathy. Other
      toxicities were grade 2 or below. CONCLUSION: This study demonstrated that
      amifostine has the potential to be a broad spectrum cytoprotectant of normal
      tissues from toxicity caused by chemotherapy and no effect on therapeutic outcome
      in lung cancer patients.

PMID- 15560692
TI  - Hiccups and multiple sclerosis.
AB  - Hiccups is a rare and unfamiliar presenting symptom of multiple sclerosis.
      Patients admitted to Ramathibodi Hospital from 1969 to 1992 who had a clinical
      diagnosis of multiple sclerosis were reviewed The presenting symptoms and
      neurological signs were analysed. The clinical features and course of the disease
      of cases who initially presented with intractable hiccups were studied in detail.
      There were 4 cases out of a total of 47 cases (8.5%) who presented with hiccups.
      These patients all had relapse and remission and two of them had a rather
      fulminant course of illness. Therefore, multiple sclerosis should be seriously
      considered as a possible cause of intractable hiccups. It may be of benign or
      malignant form. In the latter, the patients may develop quadriparesis within
      hours or days and respiratory failure may ensue. They usually respond well to
      high dose intravenous corticosteroids especially pulse methylprednisolone.

PMID- 15560693
TI  - Long-term outcome and factors influencing the outcome of thymectomy for
      myasthenia gravis.
AB  - Thymectomy has gained widespread acceptance as a treatment for patients with
      myasthenia gravis (MG). Patients with myasthenia gravis who had undergone
      thymectomy by extended transsternal approach between 1981 and 1987 were
      retrospectively reviewed to evaluate the result of thymectomy, time to remission,
      time to maximum improvement and factors influencing remission after thymectomy.
      There were 128 patients, 45 men and 83 women and the mean ages at the time of
      thymectomy were 35.7 and 32.2 years respectively. After thymectomy, 41.2% of the
      patients were in remission, 53% improved and 5.8% had no response. The remission
      rates at 1, 2, 5 and 10 years after thymectomy were 9%, 17%, 37% and 53%
      respectively and the median time to remission was 9 years. The maximum
      improvement rates at 1, 2, 5 and 10 years after thymectomy were estimated to be
      30%, 40%, 57% and 78% respectively and the median time to maximum improvement was
      3.6 years. Patients with ocular MG, longer duration of symptoms before thymectomy
      and atrophic thymus gland appeared to take longer to achieve remission although
      none of the factors was significantly associated with the time to remission.
      Thymectomy is beneficialfor MG patients with satisfactory remission and
      improvement rates. It is recommended that thymectomy should be advocatedfor these
      patients early in the course of the disease because the duration of the symptoms
      appeared to be the main determinant of the outcome.

PMID- 15560694
TI  - Differentiation of dementia with Lewy bodies, Alzheimer's disease and vascular
      dementia by cardiac 131I-meta-iodobenzylguanidine (MIBG) uptake (preliminary
      report).
AB  - OBJECTIVE: Differentiation of dementia with Lewy bodies (DLB), vascular dementia
      (VAD), and Alzheimer's disease (AD) is difficult in clinical practice. Several
      new techniques have been used for differentiation of various types of dementia.
      Among these techniques 123I-meta-iodobenzylguanidine (MIBG) uptake was reported
      to have benefit in distinguishing DLB from AD. The authors study the role of MIBG
      as a tool for differentiation of DLB, AD and VAD. METHOD: Patients with dementia
      were recruited to the study by DSMIIIR criteria. Diagnosis of each dementia type
      was made by standard clinical criteria. Brain imagings and 131I-MIBG uptake were
      performed in all the studied patients. RESULTS: Five DLB, 3 AD and 3 VAD patients
      were clinically diagnosed. The heart/mediastinum (H/M) ratio in 4 out of 5 in DLB
      was significantly lower than H/M ratio in patients with AD and VAD. AD patients
      had the highest uptake of MIBG MIBG uptake of VAD patients was in the range
      between AD and DLB but the values were close to the AD group. CONCLUSIONS: 131I
      MIBG is helpful in differentiating DLB from AD.

PMID- 15560695
TI  - Early containment of severe acute respiratory syndrome (SARS); experience from
      Bamrasnaradura Institute, Thailand.
AB  - BACKGROUND: On March 11, 2003, a World Health Organization (WHO) physician was
      admitted to Bamrasnaradura Institute, after alerting the world to the dangers of
      severe acute respiratory syndrome (SARS) in Vietnam and developing a fever
      himself. Specimens from the first day of his admission were among the first to
      demonstrate the novel coronavirus, by culture, reverse transcription-polymerase
      chain reaction (RT-PCR), and rising of specific antibody, but proper protective
      measures remained unknown. The authors instituted airborne, droplet and contact
      precautions from the time of admission, and reviewed the efficacy of these
      measures. MATERIAL AND METHOD: A specific unit was set up to care for the
      physician, beginning by roping off an isolated room and using a window fan to
      create negative pressure, and later by constructing a glass-walled antechamber,
      designated changing and decontamination areas, and adding high-efficiency
      particulate air (HEPA) filters. The use of personal protective equipment (PPE)
      was consistently enforced by nurse managers for all the staff and visitors,
      including a minimum of N95 respirators, goggles or face shields, double gowns,
      double gloves, full head and shoe covering, and full Powered Air Purifying
      Respirator (PAPR) for intubation. To assess the adherence to PPE and the
      possibility of transmission to exposed staff a structured questionnaire was
      administered and serum samples tested for SARS coronavirus by enzyme-linked
      immunosorbent assay (ELISA). Exposure was defined as presence on the SARS ward or
      contact with laboratory specimens, and close contact was presence in the
      patient's room. RESULTS: The WHO physician died from respiratory failure on day
      19. 112 of 129 exposed staff completed questionnaires, and the 70 who entered the
      patient's room reported a mean of 42 minutes of exposure (range 6 minutes-23.5
      hours). 100% reported consistent handwashing after exposure, 95% consistently
      used a fit-tested N95 or greater respirator, and 80% were fully compliant with
      strict institutional PPE protocol. No staff developed an illness consistent with
      SARS. Serum samples from 35 close contacts obtained after day 28 had a negative
      result for SARS coronavirus antibody. CONCLUSIONS: Hospitalization of one of the
      earliest SARS patients with documented coronavirus shedding provided multiple
      opportunities for spread to the hospital staff, but strict enforcement of
      conservative infection control recommendations throughout the hospitalization was
      associated with no transmission.

PMID- 15560696
TI  - Rehbein's procedure in 73 cases of Hirschsprung's disease.
AB  - The principle for treatment of Hirschsprung's disease by Rehbein's procedure is
      to remove the aganglionic narrow segment including the dilated sigmoid colon by
      dissection of the upper rectum deep down into the pelvic cavity about 2 cm from
      peritoneal reflection and to elimination of the achalasia of internal anal
      sphincter by vigorous dilatation. Between August 1987 and April 2000, 73 cases of
      Hirschsprung's disease (50 boys and 23 girls) were operated on by Rehbein's
      procedure at the Pediatric Surgical Unit, Ratchaburi Hospital. The age varied
      from 7 months to 10 years. 55 cases showed very good results by daily stool
      evacuation without any help, occasional laxative or enema in 15 cases, giving
      laxative or enema regularly in 2 cases and no adequate bowel evacuation despite
      giving laxative or enema in I case. In conclusion, Rehbein's procedure is
      technically simple and has good results. It should be another treatment of choice
      for Hirschsprung's disease.

PMID- 15560697
TI  - Noninvasive transcutaneous bilirubin as a screening test to identify the need for
      serum bilirubin assessment.
AB  - Hyperbilirubinemia is a common problem in the newborn infant. It can progress to
      develop kernicterus unless intervention is initiated. Severity and decision for
      management are usually based on serum bilirubin (TsB) which needs blood sampling.
      Transcutaneous bilirubin measurement is a noninvasive technique and the result
      correlates closely with TsB. A new transcutaneous bilirubinometer, Minolta
      AirShields Jaundice Meter, JM103, has been introduced The objectives of this
      study were: 1) To evaluate the accuracy of transcutaneous bilirubin (TcB)
      measured by JM 103, when compared to TsB, used clinically in a hospital setting
      (Leica Unistat Bilirubinometer) and 2) To develop a cut-off point of TcB level
      which indicated the need for serum bilirubin assessment. Three hundred and eighty
      eight term and near-term newborn infants with 460 paired TcB-TsB specimens were
      studied from August to November 2003. Birth weight was 3117.57 +/- 424.82 grams.
      TsB ranged from 4 to 19.6 mg/dL (x 10.5, SD 2.46). The correlation coefficient
      between TcB and TsB was significant (r 0.8, p < 0.001). TcB showed a tendency to
      underestimate TsB, with mean difference of 0.7 mg/dL, SD 1.6 mg/dL, and 95%
      confidence interval 0.85 and 0.55 mg/dL. TcB values of 8, 9, 10, 12 mg/dL were
      chosen as cut-off points that indicated the need for blood sampling for TsB
      (corresponded to hour-specific levels of 10, 12, 13 and 15 mg/dL, respectively
      when phototherapy should be initiated). In conclusion, noninvasive TcB assessment
      demonstrates significant accuracy, compared to TsB. It can be used as a screening
      test to identify the need for blood sampling for serum bilirubin level.

PMID- 15560698
TI  - Clinical abnormalities, intervention program, and school attendance of Down
      syndrome children in southern Thailand.
AB  - BACKGROUND: Down syndrome is the most common chromosomal abnormality with an
      incidence of 1:700 livebirths. In southern Thailand, most Down syndrome patients
      are referred to Songklanagarind Hospital for surgical, medical treatment and/or
      stimulation intervention. OBJECTIVE: To study the clinical features and school
      attendance of Down syndrome children. MATERIAL AND METHOD: A total of 295 Down
      syndrome children attended Songklanagarind Hospital. The clinical features of
      Down syndrome, percentage of children receiving the stimulation intervention
      program, and attending school were studied. RESULTS: Congenital heart disease was
      found in 38.6%, gastrointestinal anomalies 16.9%, hematologic malignancy 6.1%,
      and thyroid disorders 11.4%. The mortality rate of Down syndrome children was
      13.2%. Most children (65.6%) received the early stimulation, but only 38.9%
      attended the speech intervention program within the first 2 years of life. Of the
      total 109 Down syndrome children aged over 5 years that are still being followed,
      only 74 (67.9%) attended school. The school attendance was correlated with the
      family income, but not correlated with the level of maternal or paternal
      education. CONCLUSION: Congenital heart disease and gastrointestinal anomalies
      are commonly found in Down syndrome children. Most children received an early
      intervention program, but only 38.9% received speech intervention. In children
      aged >5 years, only 68% attended school, and school attendance was correlated
      with the family income.

PMID- 15560699
TI  - Hemifacial spasm: results of treatment with low dose botulinum toxin injection.
AB  - BACKGROUND: Hemifacial Sapsm (HFS) is a common movement disorder in Thailand.
      Botulinum toxin type A (BTA) is an effective and safe treatment for this
      condition. The success of BTA treatment depends on the experience of the
      clinician. OBJECTIVE: To study the demographic data, efficacy and safety of low
      dose BTA injection in HFS patients. SETTING: The Spastic and Dystonia Clinic,
      Department of Rehabilitation Medicine, King Chulalongkorn Memorial Hospital.
      DESIGN: Open-label, prospective case-series study. PATIENTS: All patients with
      HFS referred for BTA injection from December 1st, 1995 to November 30th, 2003.
      METHOD: Sex, age, side of spasm, onset of symptoms before BTA injection,
      underlying diseases, sites of BTA injection, dose of each BTA treatment, duration
      of response, efficacy, and side-effects were analyzed. 3-5 units of BOTOX were
      intramuscularly injected per site to all muscles that had spasm. After injection,
      a 20-minute cold compression on the first day was followed by 20-minute warm
      compression with massage at each injection site per day for 14 days. RESULTS: A
      total of 112 patients with HFS were treated with 874 BTA treatments. There were
      71 females (63.4%) and 41 males (36.6%). The mean age was 45 years. 75 patients
      (67%) were affected on the left side. Mean duration of symptoms was 3.4 years.
      The sites of injection were orbicularis occuli and orbicularis oris muscles in
      all 874 treatments (100%). The mean dose of all treatments was 25 units. The mean
      initial dose was 30.5 units. The mean dose for subsequent injection was 23 units.
      The mean duration between treatments was 4.7 months. The mean initial duration
      was 3.5 months. The mean duration for subsequent injection was 4.8 months. The
      outcomes of treatment assessed at 4 weeks after injection classified as excellent
      (>80% improvement) were found in 845 treatments (96.7%). Most treatments had no
      complication (91.9%). Ptosis, facial paresis and double vision were mild and
      transient, lasting 1-4 weeks. There were no long-term complications of BTA
      treatment in the present series. CONCLUSION: Low dose BTA injection is an
      effective treatment for hemifacial spasm patients. There was a longer duration of
      response in subsequent injections and a lower complication rate in the present
      study when compared to others.

PMID- 15560700
TI  - Anatomical study of the maxillary artery at the pterygomaxillary fissure in a
      Thai population: its relationship to maxillary osteotomy.
AB  - BACKGROUND: The maxillary artery (MA) and its terminal branches are commonly
      damaged in the maxillary osteotomy, especially during separation of the
      pterygomaxillary junction (PMJ). OBJECTIVE: To evaluate the positional
      relationship between the MA at the pterygomaxillary fissure (PMF) and the PMJ in
      Thais, as well as to measure the diameter of the MA as it enters the
      pterygopalatine fossa (PPF) and the heights of PMJ, maxillary tuberosity and
      posterior maxilla. SUBJECTS AND METHOD: Both sides of 100 Thai adult cadavers (50
      males and 50 females) were examined The mean age of the subjects was 64.5 +/-
      12.8 years. With the lateral infratemporal approach, the branches from the third
      part of the MA, PMJ and posterolateral maxilla were dissected. Measurements taken
      included the following: First, the distance from the most inferior point of the
      PMJ to the most inferior position of the MA as it entered the PPF; second, the
      external diameter of the MA as it entered the PPF; third, vertical heights of the
      PMJ, maxillary tuberosity and posterior maxilla. Means, standard deviations and
      ranges were determined and statistical differences were calculated between sides
      and genders at p < 0. 05. RESULTS: The MA entered the PPF at a mean distance of
      23.5 +/- 2.5 mm above the most inferior point of the PMJ. The mean external
      diameter of the MA as it entered the PPF was 2.8 +/- 0.6 mm. The mean heights of
      the PMJ, maxillary tuberosity and posterior maxilla were 19.5 +/- 2.3 mm, 6.1 +/-
      2.7 mm, and 25.6 +/- 3.3 mm, respectively. There were no differences with respect
      to side and gender, except that the distance from the most inferior point of the
      PMJ to the most inferior position of the MA as it entered the PPF was longer in
      males than in females (p < 0.05). CONCLUSION: The mean location of the MA was
      23.5 mm apart from the most inferior point of the PMJ, therefore, dysjunction of
      the PMJ using an osteotome with a 15-mm cutting edge may be conducted without
      damaging to the MA. When properly placed, the margin of safety from the superior
      cutting edge of the osteotome to the MA is approximately 8 mm in adults.

PMID- 15560701
TI  - Evaluation of enzyme-linked immunosorbent assay and indirect hemagglutination
      assay for detection of leptospiral antibody by using three different antigens.
AB  - Evaluation of enzyme linked immunosorbent assay (ELISA) and indirect
      hemagglutination assay (IHA) for detection of leptospiral antibody were performed
      using three different soluble antigens extracted from Leptospira interrogans
      serovar Bataviae including heat extracted antigen (HEA), sonicated antigen (SA)
      and deoxycholate extracted antigen (DEA). One hundred seventy-eight sera from 85
      confirmed leptospirosis cases and 202 non-leptospirosis cases were examined SA
      IHA showed the highest sensitivity of 98.8% followed by SA-ELISA-IgM and DEA
      ELISA-IgM which showed an equal sensitivity of 97.6%. SA-ELISA-IgM was the most
      specific (96.5%) test followed by DEA-ELISA-IgM and SA-IHA which gave an equal
      specificity of 94.1%. The IgG-ELISA tests were less sensitive and specific than
      the others. These data indicated that the IgG-ELISA tests were not suitable as
      diagnostic tests for acute leptospirosis in humans. Using acute phase sera the
      sensitivity of DEA-ELISA-IgM, SA-ELISA-IgM and HEA-ELISA-IgM were 22.4%, 20.0%
      and 20.0% respectively, while those of the IgG ELISA tests were 32.9%, 17.6% and
      10.6% respectively, the sensitivity of SA-IHA and DEA-IHA were 22.4% and 10.6%
      respectively. In conclusion, both the IgM-ELISA tests using SA and DEA and the
      IHA using SA are not different in diagnosis of human leptospirosis. SA is the
      most suitable antigen for detection of leptospiral antibody by IgM ELISA and IHA.

PMID- 15560702
TI  - Balance disorders in the elderly and the benefit of balance exercise.
AB  - Symptoms of balance disorders including 'unsteadiness', 'dizziness and vertigo'
      are common in the elderly and commonly found in general practice in medicine.
      There are many causes of balance disorders and vary from one person to another.
      Disorder of the internal ear or vestibular end-organ type is one cause.
      Unsteadiness of somato-sensory or proprioception is common in the elderly so is
      degenerative disorder of central control in brain. The elderly are prone to many
      chronic illnesses or disorders which are causes of balance disorder or give rise
      to more rapid degeneration of the central nervous system i.e. high blood
      pressure, diabetes mellitus, heart disease, proprioception and joint problems,
      arthritis and muscular weakness due to lack of good health and exercise. The
      objectives of this research study were to find the etiologies of balance
      disorders and how Balance Exercises and the 'National Health Service' can be of
      benefit in helping to prevent them. 1565 elderly inhabitants (age > or = 60
      years) of 20 communities adjacent to Siriraj Hospital were selected for study.
      Among these, 625 persons had a history of balance disorders. Among those, 256 had
      symptoms during the week selected for examination. The average age was 66 years
      old, women outnumbered men with a ratio of 2.4:1. The common underlying causes
      were hypertension in 32.4%, diabetes mellitus 13.8%, arthritis 8.1%, and heart
      disease 4.4% respectively. All are still taking one or more types of drug. The
      subjects were randomly divided into two groups for the study purpose of
      effectiveness of balance exercise. Group 1 did not perform the head balance
      exercise and Group 2 performed the head balance exercise. Audiometric testing
      showed impaired hearing in 90% of the subjects. The majority slowed hearing loss
      in high frequencies. Testing of middle ear function found 75% of Group 1 to have
      normal middle ear function 77% of Group 2. Brainstem Electrical Response
      Audiometry (BERA) showed normal response latencies of in 96% of group 1 and 94%
      of Group 2. Poor morphology of waveform was found in 12% of Group 1 and 16% of
      Group 2. Doppler sonography for intra-cranial blood flow measurement showed
      abnormal flow of the ICA in 17.6% of group 1 and 20.16% of group 2. Basilar
      arterial abnormal flow was found in 77.6% of Group 1 and 80.6% of Group 2
      respectively. The flow of ICA was improved after 8 weeks in both groups. The
      measurement of balance by Posturography showed 86.7% abnormality in Group 1 and
      83.5% abnormality in Group 2 (and the majority due to inner ear problems but many
      cases had a mixture of joints and CNS problems too). Results of the self
      evaluation (by questionaires) showed the elderly to have symptoms of light
      headedness in 51% and loss of balance in 29%, Vertigo with rotation occurred in
      23.6%. 49% of the symptoms were intermittent, 56.4% experienced a 'fall". On
      questioning about the benefit and performance of Head and Neck Exercises, 82.8%
      found the exercises were easy to perform, 56.4% said the results were very
      beneficial.

PMID- 15560703
TI  - An experience with intubating laryngeal mask airway for difficult airway
      management: report on 38 cases.
AB  - A retrospective study was performed on 38 patients (23 males and 15 females) in
      whom the intubating laryngeal mask airway (ILMA) was used for airway management
      at Srinagarind and Siriraj Hospital in 2003. The patients 'age and weight ranged
      between 12 and 75 years and 40 and 94 kg, respectively. Difficult tracheal
      intubation was suspected before starting general anesthesia in 17 patients,
      whereas it was found difficult after induction of general anesthesia in 21. The
      ILMA was successfully placed in all patients with airway patency classified as
      'good' and 'acceptable' in 36 patients (94.7%), and 'poor' in two. Oxygen
      saturation during intubation was maintained above 95 percent in all patients.
      Tracheal intubation through the ILMA was successful in 34 patients (89.5%), which
      was described as 'easy' in 27 of 34 patients (79.4%). In the remaining 7, 2-5
      attempts were required for successful tracheal intubation. The types of
      endotracheal tubes used were: 1) the pre-formed silicone tube in 55.9 percent, 2)
      the pre-formed flexible tube in 41.2 percent; and, 3) the standard polyvinyl tube
      in 2.9 percent. In the four patients with failed tracheal intubation through the
      ILMA, three were successfully intubated with conventional laryngoscopy and one
      with gum elastic bougie. There were no serious complications following the use of
      the ILMA in these patients. The ILMA proved a safe, very useful and easy to use
      device with a high success rate for difficult airway management.

PMID- 15560704
TI  - Bilateral extraordinary huge, multi-compartmental tuberculous abscesses: a case
      report.
AB  - OBJECTIVE: To illustrate computerized tomography (CT) and magnetic resonance
      imaging (MRI) findings of tuberculous spondylitis with extensive abscess
      collections. METHOD: A review of one patient with tuberculous spondylitis and
      extensive paraspinal, subligamentous, retroperitoneal, and subcutaneous abscesses
      including pertinent history, important physical examination, CT and MR imaging
      findings was performed. RESULT AND CONCLUSION: This case demonstrates multiple
      patterns of tuberculous abscess formation secondary to spinal tuberculosis;
      included are paraspinal, subligamentous, retroperitoneal, and subcutaneous
      locations. The extension of the abscess should be kept in mind when treating a
      patient with tuberculous spondylitis. MR imaging is a modality of choice to
      illustrate full extension of the disease process, which is necessary for
      therapeutic decision making and planning.

PMID- 15560705
TI  - Spinal cord compression and bilateral sensory neural hearing loss: an unusual
      manifestation of neurocysticercosis.
AB  - Neurocysticercosis is the most common parasitic infestation involving the central
      nervous system in tropical countries. Common presentations are seizure,
      meningitis and increased intracranial pressure. The authors report a case of a 52
      year-old woman with racemose neurocysticercosis in the subarachnoid space at the
      cistern of the brain through the lumbar cistern. She presented with progressive
      paraparesis due to spinal cord compression and finally had progressive bilateral
      sensori-neural hearing loss. MRI brain and the whole spinal cord revealed
      numerous rim-enhancing cystic lesions at the basal cistern, prepontine cistern,
      bilateral cerebellopontine angle, internal acoustic canals, intramedullary lesion
      at the 5th cervical spinal level, lumbar cistern lesions and secondary
      syringomyelia at the thoracic spinal cord. The histopathologic examination
      confirmed cysticercosis. After treatment by albendazole and surgical removal, she
      still developed recurrent spinal compression at a higher level and obstructive
      hydrocephalus. Finally, she died from status epilepticus and septic shock.

PMID- 15560706
TI  - The use of clinical practice guideline on hyperbilirubinemia: rule or guideline.

PMID- 15560707
TI  - Medical research ethics in Thailand: what should be the most appropriate
      approach? An analysis based on Western ethical principles.
AB  - An approach to the ethical consideration of medical research in Thailand is
      presented in terms of Western principles. It is argued that at the present time
      the principle of therapeutic beneficence is to be considered a priority over
      respect for autonomy, expressed as informed consent. This approach is especially
      recommended for therapeutic research in an inpatient hospital setting in
      Thailand. Only when valid and effective informed consent processes have been
      developed should respect for autonomy be given more weight in research ethics
      considerations. The discussion is presented within the context of recent
      developments in the field of bioethics and in light of some recent findings in
      informed consent research both in and outside of Thailand.

PMID- 15560708
TI  - Medical ethics: on air.

PMID- 15560710
TI  - The role of magnetic resonance imaging in diagnosis and management of breast
      cancer.
AB  - A review of the literature on the current applications of breast magnetic
      resonance imaging (MRI) indications, their rationale and their place in diagnosis
      and management of breast cancer was given. Contrast-enhanced breast MRI is
      developing as a valuable adjunct to mammography and sonography. Its high
      sensitivity for invasive breast cancer establishes its superiority in evaluation
      of multifocality/multicentricity, tumor response to neoadjuvant chemotherapy,
      detection of recurrence, and staging. Emerging applications include spectroscopy,
      usage of new contrast agents, and MRI-guided interventions, including noninvasive
      treatment of breast cancer. Its potential benefit in screening high-risk women
      has yet to be established with prospective studies, particularly with regard to
      false positive results.

PMID- 15560711
TI  - Multiparametric and multinuclear magnetic resonance imaging of human breast
      cancer: current applications.
AB  - The exploration of novel imaging methods that have the potential to improve
      specificity for the identification of malignancy is still critically needed in
      breast imaging. Changes in physiologic alterations of soft tissue water
      associated with breast cancer can be visualized by magnetic resonance (MR)
      imaging. However, it is unlikely that a single MR parameter can characterize the
      complexity of breast tissue. Techniques such as multiparametric MR imaging,
      proton magnetic resonance spectroscopic (MRSI) imaging, and 23Na sodium MR
      imaging when used in combination provide a comprehensive data set with
      potentially more power to diagnose breast disease than any single measure alone.
      A combination of MR, MRSI, and 23Na sodium MR parameters may be examined in a
      single MR imaging examination, potentially resulting in improved specificity for
      radiologic evaluation of malignancy.

PMID- 15560712
TI  - Determination of grade and receptor status from the primary breast lesion by
      magnetic resonance spectroscopy.
AB  - Magnetic resonance spectra (MRS) from fine needle aspiration biopsies (FNAB) from
      primary breast lesions were analysed using a pattern recognition method,
      Statistical Classification Strategy, to assess tumor grade and oestrogen receptor
      (ER) and progesterone receptor (PgR) status. Grade 1 and 2 breast cancers were
      separated from grade 3 cancers with a sensitivity and specificity of 96% and 95%,
      respectively. The ER status was predicted with a sensitivity of 91% and a
      specificity of 90%, and the PgR status with a sensitivity of 91% and a
      specificity of 86%. These classifiers provide rapid and reliable, computerized
      information and may offer an objective method for determining these prognostic
      indicators simultaneously with the diagnosis of primary pathology and lymph node
      involvement.

PMID- 15560713
TI  - Differentiating surgical from non-surgical lesions using perfusion MR imaging and
      proton MR spectroscopic imaging.
AB  - Advanced MRI techniques, such as MR spectroscopy, diffusion and perfusion MR
      imaging can give important in vivo physiological and metabolic information,
      complementing morphologic findings from conventional MRI in the clinical setting.
      Combining perfusion MRI and MR spectroscopy can help in patients with brain
      masses in who the pre-operative differential diagnosis is unclear. This review
      demonstrates the use of dynamic, susceptibility weighted, contrast-enhanced MR
      imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI) to
      distinguish surgical from non-surgical lesions in the brain. There is overlap in
      the MRI appearance of many enhancing and ring-enhancing lesions such as gliomas,
      metastases, inflammatory lesions, demyelinating lesions, subacute ischemia,
      abscess and some AIDS related lesions. We review examples of histopathologically
      confirmed high-grade glioma, a middle cerebral artery territory infarct, a
      tumefactive demyelinating lesion and a metastasis for which conventional MR
      imaging (MRI) was non-specific and potentially misleading and demonstrate how DSC
      MRI and MRSI features were used to increase the specificity of neurodiagnosis. At
      several institutions, many patients routinely undergo MRI as well as MRSI and DSC
      MRI. Cerebral blood flow (CBF), mean transit time (MTT), and relative cerebral
      blood volume (rCBV) measurements are obtained from regions of maximal perfusion
      as determined from perfusion color overlay maps. Metabolite levels and ratios are
      determined for Choline (Cho), N-Acetyl Aspartate (NAA), Lactate and Lipids (LL).
      Metabolite levels are obtained by measuring the peak heights of each metabolite
      and the ratios are obtained from these measurements for Cho/Cr, Cho/NAA and
      NAA/Cr. Neurosurgical intervention carries substantial morbidity, mortality,
      financial and potential emotional cost to the patient and family. Making a pre
      operative diagnosis allows the neurosurgeon to be confident in the choice of
      treatment plan for the patient and allays considerable patient anxiety. The
      utility of combining clinical findings with multi-parametric information from
      perfusion and spectroscopic MR imaging in differentiating surgical lesions from
      those which do not require surgical intervention is discussed.

PMID- 15560714
TI  - The role of diffusion tensor imaging in establishing the proximity of tumor
      borders to functional brain systems: implications for preoperative risk
      assessments and postoperative outcomes.
AB  - Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to
      directional movements of water molecules, induced by tissue barriers. This
      provides a new form of contrast that allows the identification of functional
      white matter tracts within the brain, and has been proposed as a technique
      suitable for presurgical planning in brain tumor patients. Resection of primary
      brain tumors improves survival, functional performance, and the effectiveness of
      adjuvant therapies, provided that surgically-induced neurological deficits can be
      avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial
      relationships between eloquent white matter and tumor borders, provide
      information essential to preoperative planning, and improve the accuracy of
      surgical risk assessments preoperatively. We present our experience in a series
      of 28 brain tumor patients where the integration of functional magnetic resonance
      imaging (fMRI) and DTI data was used to determine key anatomic spatial
      relationships preoperatively. Twice as many functional systems were localized to
      within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative
      planning, compared to that afforded by fMRI alone. Our results show that the
      combined use of fMRI and DTI can provide a better estimation of the proximity of
      tumor borders to eloquent brain systems sub-serving language, speech, vision,
      motor and premotor functions. Additionally, a low regional complication rate (4%)
      observed in our series suggests that preoperative planning with these combined
      techniques may improve surgical outcomes compared to that previously reported in
      the literature. Larger studies specifically designed to establish the accuracy
      and predictive value of DTI in brain tumor patients are warranted to substantiate
      our preliminary observations.

PMID- 15560715
TI  - Abnormal vessel tortuosity as a marker of treatment response of malignant
      gliomas: preliminary report.
AB  - Despite multiple advances in medical imaging, noninvasive monitoring of
      therapeutic efficacy for malignant gliomas remains problematic. An underutilized
      observation is that malignancy induces characteristic abnormalities of vessel
      shape. These characteristic shape abnormalities affect both capillaries and much
      larger vessels in the tumor vicinity, involve larger vessels prior to sprout
      formation, and are generally not present in hypervascular benign tumors. Vessel
      shape abnormalities associated with malignancy thus may appear independently of
      increase in vessel density. We hypothesize that an automated, computerized
      analysis of vessel shape as defined from high-resolution MRA can provide valuable
      information about tumor activity during the treatment of malignant gliomas. This
      report describes vessel shape properties in 10 malignant gliomas prior to
      treatment, in 2 patients in remission during treatment, and in 2 patients with
      recurrent disease. One subject was scanned multiple times. The method involves an
      automated, statistical analysis of vessel shape within a region of interest for
      each tumor, normalized by the values obtained from the vessels within the same
      region of interest of 34 healthy subjects. Results indicate that untreated tumors
      display statistically significant vessel tortuosity abnormalities. These
      abnormalities involve vessels not only within the tumor margins as defined from
      MR but also vessels in the surrounding tissue. The abnormalities resolve during
      effective treatment and recur with tumor recurrence. We conclude that vessel
      shape analysis could provide an important means of assessing tumor activity.

PMID- 15560716
TI  - Correlation of MR perfusion imaging and vessel tortuosity parameters in
      assessment of intracranial neoplasms.
AB  - Advances in noninvasive imaging techniques such as magnetic resonance perfusion
      imaging have been found useful in grading cerebral neoplasms and have potential
      for significant clinical benefit. The purpose of this study was to determine the
      correlation between tumor vessel tortuosity as measured from vessels extracted
      from magnetic resonance angiograms (MRA) and perfusion parameters of cerebral
      blood flow (CBF) and cerebral blood volume (CBV) in intracranial neoplasms. We
      hypothesized that tumor blood vessel tortuosity measures and perfusion measures
      would be correlated, since both are increased by tumor angiogenesis. 18 patients
      with 19 cerebral neoplasms were evaluated with conventional MR imaging and
      dynamic contrast-enhanced T2-weighted perfusion MR imaging (PWI). Both benign and
      malignant lesions were included, as were hyper- and hypovascular tumors. Regions
      of interest were plotted within the tumor area to locate foci of maximum CBV and
      CBF. CBV and CBF measurements were also recorded in contralateral normal
      appearing white matter to calculate relative CBV (rCBV) and relative CBF (rCBF).
      Vessel tortuosity analyses were conducted upon vessels segmented from MRA images
      of the same patients using two tortuosity descriptors (SOAM and ICM), which have
      previously been demonstrated to have efficacy in separating benign from malignant
      disease. Linear regression analyses were conducted to determine if correlations
      exist between CBV or CBF and the two tortuosity measurements. For the overall set
      of tumors, no significant correlations were found between flow or volume measures
      and the tortuosity measures. However, when the 7 glioblastoma multiforme tumors
      were examined as a subgroup, the following significant correlations were found:
      rCBV and SOAM (R2=0.799), rCBV and ICM (R2=0.214). Our results demonstrate that
      MR perfusion imaging data do not correlate significantly with vessel tortuosity
      parameters as determined from the larger vessels seen by MRA. However, for
      subgroups of a particular tumor type such as GBM, there may be significant
      correlations. It appears that perfusion and tortuosity data may provide
      independently useful data in the assessment of cerebral neoplasms.

PMID- 15560717
TI  - Quantitative pathology in tissue MR spectroscopy based human prostate
      metabolomics.
AB  - At present, the clinical utility of metabolomic profiles of human prostate tissue
      relies on the establishment of correlations between metabolite data and clinical
      measurements, particularly pathological findings. Because metabolomics is a
      quantitative study, its clinical value can be rigorously investigated by
      determining its association with other quantitative measures. The human visual
      assessment of prostate tissue, however, introduces both inter- and intra-observer
      biases that may limit the reliability of its quantitations, and therefore, the
      strength of its correlations with metabolomic profiles. The aim of this study was
      to develop a simple, feasible protocol for the computer-aided image analysis
      (CAIA) of prostate pathology slides in order to achieve quantitative pathology
      from tissue samples, following metabolomic measurement with high-resolution magic
      angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Thirty-eight
      samples from 29 prostatectomy cases were studied with HRMAS MRS. After
      spectroscopy analysis, samples were serial-sectioned, stained and visually
      assessed by pathologists. Cross-sections from these samples were then measured
      with the CAIA protocol. Results showed a two-fold difference between human visual
      assessments of the area percentages of tissue pathologies and CAIA area
      percentages obtained for the same features. Linear correlations were found
      between both metabolites indicative of normal epithelium and those indicative of
      prostate cancer, and the CAIA quantitative results. CAIA based quantitative
      pathology is more reliable than human visual assessment in establishing
      correlations useful for disease diagnosis between prostate pathology and
      metabolite concentrations.

PMID- 15560718
TI  - Resolution and contrast in magnetic resonance electrical impedance tomography
      (MREIT) and its application to cancer imaging.
AB  - It has been reported that the electrical impedance of malignancies could be 20-40
      times lower than healthy tissues and benign formations. Therefore, in vivo
      impedance imaging of suspicious lesions may prove to be helpful in improving the
      sensitivity and specificity of detecting malignant tumors. Several systems have
      been developed to map the conductivity distribution inside a volume of tissue,
      however they suffer from poor spatial resolution because the measurements are
      taken only from surface electrodes. MRI based impedance imaging (MREIT) is a
      novel method, in which weak electrical currents are injected into the tissue and
      the resulting perturbations in the magnetic field are measured using MRI. This
      method has been shown to provide better resolution compared to previous
      techniques of impedance imaging because the measurements are taken from inside
      the object on a uniform grid. Thus, it has the potential to be a useful modality
      that may detect malignancies earlier. Several phantom imaging experiments were
      performed to investigate the spatial resolution and dynamic range of contrast of
      this technique. The method was also applied to a live rat bearing a R3230 AC
      tumor. Tumor location was identified by contrast enhanced imaging.

PMID- 15560719
TI  - Quantitative assessment of percent breast density: analog versus digital
      acquisition.
AB  - Breast density is a moderate risk factor for breast cancer based on quantitative
      measurement of percent breast density from film-screen mammograms. In this study,
      percent breast density was determined using computer-assisted interactive
      thresholding software from sixty consecutive mammograms of women undergoing
      digital screening mammography with a prior film-screen mammogram obtained within
      the last two years. Observations were made regarding discrepancies in density
      readings. Percent breast density was significantly lower for digital mammograms
      (mean 32.2%) compared to analog mammograms (mean 40.3%) (p<0.0001). This was not
      significant for women with less than 20% breast density (range +0.3 to -2.7%),
      but larger differences were seen with increasing density (12.5-14.9% lower for
      >50% density). Differences in density readings between analog and digital
      mammography were largely observed to be due to better recognition of the skin
      line on digital mammograms resulting in inclusion of more subcutaneous fat.
      Difficulties with appropriate recognition of subcutaneous breast tissue and fatty
      tissue near the chest wall were present for both analog and digital mammography.
      In conclusion, percent breast density is significantly lower when the mammogram
      is acquired in digital format compared to film-screen, largely due to better
      recognition of the skin line with resultant inclusion of more subcutaneous fat.
      Breast cancer risk predictions based on computerized assessment of breast density
      may be underestimated when applied to digital mammography.

PMID- 15560720
TI  - Imaging of the ovary.
AB  - Epithelial ovarian cancer has the highest mortality rate among the gynecologic
      cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian
      cancer. Detection before the disease has spread beyond the ovary would
      significantly improve the survival from ovarian cancer, which is currently only
      30% over 5 years, despite extensive efforts to improve the survival. This study
      describes initial investigation of the use of optical technologies to improve the
      outcome for this disease by detecting cancers at an earlier and more treatable
      stage. Women undergoing oophorectomy were recruited for this study. Ovaries were
      harvested for fluorescence spectroscopy, confocal microscopy, and optical
      coherence tomography. Fluorescence spectroscopy showed large diagnostic
      differences between normal and abnormal tissue at 270 and 340 nm excitation.
      Optical coherence tomography was able to image up to 2mm deep into the ovary with
      particular patterns of backscattered intensity observed in normal versus abnormal
      tissue. Fluorescence confocal microscopy was able to visualize sub-cellular
      structures of the surface epithelium and underlying cell layers. Optical imaging
      and/or spectroscopy has the potential to improve the diagnostic capability in the
      ovary, but extended systematic investigations are needed to identify the unique
      signatures of disease. The combination of optical technologies supported by
      modern molecular biology may lead to an instrument that can accurately detect
      early carcinogenesis.

PMID- 15560721
TI  - Characteristic absorbance of nucleic acids in the Mid-IR region as possible
      common biomarkers for diagnosis of malignancy.
AB  - FTIR spectroscopy has been extensively used to understand the differences between
      normal and malignant cells and tissues. In the present study, FTIR
      microspectroscopy was performed on biopsies to evaluate parameters deduced from
      changes in nucleic acid absorbance monitored at various characteristic
      wavenumbers in the Mid-IR region. The data showed that there were differences in
      the spectra of normal and malignant tissues from several organs such as colon,
      cervix, skin and blood with respect to absorbance due to nucleic acids. Similar
      results were observed in the case of cell lines that were transformed to induce
      carcinogenesis. Of the several ratios examined for consistency in differentiating
      cancer and normal tissues, the I(996 cm(-1))/I(966 cm(-1)) showed promise as a
      distinguishing parameter and was comparable to the I(1121 cm(-1))/I(1020 cm(-1))
      ratio reported in many earlier studies. The absorbance of nucleic acids is
      presented with an emphasis on the application of FTIR microspectroscopy for
      diagnosis of malignancy. Our results indicate that usage of nucleic acid
      absorbance yield statistically significant parameters, which could differentiate
      normal and cancerous tissues.

PMID- 15560722
TI  - Helical tomotherapy as a means of delivering accelerated partial breast
      irradiation.
AB  - A novel treatment approach utilizing helical tomotherapy for partial breast
      irradiation for patients with early-stage breast cancer is described. This
      technique may serve as an alternative to high dose-rate (HDR) interstitial
      brachytherapy and standard linac-based approaches. Through helical tomotherapy,
      highly conformal irradiation of target volumes and avoidance of normal sensitive
      structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike
      other linac-based techniques, it provides image-guided adaptive radiotherapy
      along with intensity modulation. A treatment planning CT scan was obtained as
      usual on a post-lumpectomy patient undergoing HDR interstitial breast
      brachytherapy. The patient underwent catheter placement for HDR treatment and was
      positioned prone on a specially designed position-supporting mattress during CT.
      The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm
      margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based
      HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were
      generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and
      chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric
      coverage of the target with helical tomotherapy was conformal and homogeneous.
      "Hot spots" (> or =150% isodose line) were present around implanted dwell
      positions in brachytherapy plan whereas no isodose lines higher than 109% were
      present in the helical tomotherapy plan. Similar dose coverage was achieved for
      lung, pectoralis muscle, heart, chest wall and breast skin with the two methods.
      We also compared our results to that obtained using conventional linac-based
      three dimensional (3D) conformal accelerated partial breast irradiation. Dose
      homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest
      wall dose is less than for either HDR brachytherapy or helical tomotherapy but
      skin and pectoral muscle doses were higher than with the other techniques. Our
      results suggest that helical tomotherapy can serve as an effective means of
      delivering accelerated partial breast irradiation and may offer superior dose
      homogeneity compared to HDR brachytherapy.

PMID- 15560723
TI  - Nanoparticle based systemic gene therapy for lung cancer: molecular mechanisms
      and strategies to suppress nanoparticle-mediated inflammatory response.
AB  - Cancer gene therapy for the treatment of lung cancer has shown promise in the
      laboratory and in Phase I/II clinical trials. However, it is currently limited to
      treating localized tumors due to host-immunity against the gene delivery vector
      and the transgene. Therefore, there is a tremendous effort to develop and test
      alternate gene delivery vectors that are efficient, non-immunogenic, and
      applicable for systemic therapy. One such gene delivery vehicle is the non-viral
      vector, DOTAP:cholesterol (DOTAP:Chol) nanoparticle. Preclinical studies from our
      laboratory has shown that DOTAP:Chol. nanoparticles are effective systemic gene
      delivery vectors that efficiently deliver tumor-suppressor genes to disseminated
      lung tumors. Based on our findings we have recently initiated a Phase-I trial for
      systemic treatment of lung cancer using a novel tumor suppressor gene, FUS1.
      Although DOTAP:Chol. nanoparticles complexed to DNA (DNA-nanoparticles) are
      efficient vectors for systemic therapy, induction of an inflammatory response in
      a dose-dependent fashion has also been observed thereby limiting its use. A
      better understanding of the underlying mechanism for DNA-nanoparticles-mediated
      inflammatory response will allow us to develop strategies to suppress
      inflammation and expand the therapeutic window in treating human cancer. In the
      present study we conducted experiments examining the mechanism of nanoparticle
      mediated inflammatory response in vitro and in vivo. We demonstrate that systemic
      administration of DNA-nanoparticles induced multiple signaling molecules both in
      vitro and in vivo that are associated with inflammation. Use of small molecule
      inhibitors against the signaling molecules resulted in their suppression and
      thereby reduced inflammation without affecting transgene expression. Our results
      provide a rationale to use small molecule inhibitors to suppress nanoparticle
      mediated inflammation when administered systemically. Further development and
      testing will allow us to incorporate this strategy into future clinical trials
      that is based on systemic non-viral vector gene therapy.

PMID- 15560724
TI  - Radiosensitization of murine Ehrlich ascites tumor by a combination of 2-deoxy-D
      glucose and 6-aminonicotinamide.
AB  - Enhanced radiosensitizing effects of a combination of 2-deoxy-D-glucose (2-DG), a
      glycolytic inhibitor and 6-aminonicotinamide (6-AN) an analogue of nicotinamide,
      which inhibits hexose monophosphate shunt (HMP) have been demonstrated in vitro.
      The purpose of the present studies is to investigate in vivo effects of this
      combination in Ehrlich ascites tumor (EAT) bearing mice. EAT tumor was grown in
      Swiss albino strain A mice. Treatment induced growth delay and tumor free animal
      survival were evaluated as parameters of radiation response. Focal irradiation of
      the tumor with a single fraction of 10 Gy induced a moderate delay in tumor
      growth but did not lead to complete regression of the tumor. Intravenous
      administration of either 6-AN or 2-DG immediately before irradiation enhanced
      radiation-induced growth delay with a cure rate of 45%. However, administration
      of a combination of 2-DG (2 g/kg b.wt.) and 6-AN (2 mg/kg b.wt.) immediately
      before irradiation led to complete regression of tumor in 80% animals resulting
      in survival of more than 300 days. A similar response (approximately 80%) was
      observed when 2-DG dose was reduced to 1 g/kg in combination with 6-AN. It is
      concluded that 6-AN enhances the radiosensitizing effects of 2-DG and the
      combination may have potential application in improving radiotherapy of tumors.

PMID- 15560725
TI  - Preventing childhood obesity: a bicycle analogy.

PMID- 15560726
TI  - My experience as NASN School Nurse of the Year.

PMID- 15560727
TI  - Marginalization and school nursing.
AB  - The concept of marginalization was first analyzed by nursing researchers Hall,
      Stevens, and Meleis. Although nursing literature frequently refers to this
      concept when addressing "at risk" groups such as the homeless, gays and lesbians,
      and those infected with HIV/AIDS, the concept can also be applied to nursing.
      Analysis of current school nursing literature and research suggests school
      nursing may be a marginalized specialty, encompassing many of the characteristics
      of marginalization including isolation, role confusion, and barriers to practice.
      School nurses can reduce or eliminate these characteristics by increasing their
      visibility and collaborative opportunities in the educational and nursing
      communities while also providing mentoring opportunities to new school nurses.

PMID- 15560728
TI  - School nurses: a resource for young worker safety.
AB  - On average, 67 youths under age 18 die at work in the United States each year,
      and many more suffer work-related injuries. In 1998, an estimated 77,000 young
      workers suffered work injuries that required treatment in hospital emergency
      rooms. It is estimated that only one third of work-related injuries are seen in
      emergency departments; therefore, the National Institute for Occupational Safety
      and Health (NIOSH) estimates that nearly 230,000 youths suffer work-related
      injuries each year. Through NIOSH's Fatality Assessment and Control Evaluation
      (FACE) program, NIOSH investigators identified poor knowledge of child labor
      laws, lack of safety training and supervision, inappropriate job assignment, and
      lack of employer compliance with labor laws as factors contributing to young
      worker deaths. School nurses serve as a resource to other professionals, parents,
      employers, and students and can help foster safer working conditions for youth by
      providing these groups with young worker safety information.

PMID- 15560729
TI  - Bloodborne infections: should they be disclosed? Is differential treatment
      necessary?
AB  - There are students and staff in many schools with hepatitis B, hepatitis C, or
      HIV infections. Should parents or guardians be expected to disclose students'
      bloodborne infections to school officials? Can infected students play contact
      sports given the increased risk of blood spills? What type of response plan
      should schools develop in the event of a blood spill to protect student health
      and privacy? This article summarizes the policies and approaches that the federal
      government and medical, school nursing, teacher, and parent organizations have
      taken on these issues. It suggests strategies school nurses can employ to protect
      the civil rights, privacy, and health of all students and school staff.

PMID- 15560730
TI  - Effect of full-time versus part-time school nurses on attendance of elementary
      students with asthma.
AB  - Asthma, the most common chronic disease in children today, is the leading cause
      of absenteeism among students. It accounts for nearly 20 million lost school days
      annually. This study examined whether full-time (5 days per week) or part-time (2
      days per week) school nurses would have a differential effect on the frequency of
      absences among elementary school students with asthma. This study found that
      students with asthma who were poor or who were African American and in schools
      with full-time nurses missed significantly fewer days (3 days, or 23% fewer
      missed days) than did their counterparts with asthma in schools with part-time
      nurses.

PMID- 15560731
TI  - Anger expression and blood pressure in adolescents.
AB  - The clinical significance of childhood hypertension is important as elevated
      pressures during childhood are found to follow a progressively increasing track
      into adulthood. Little work has been done to examine the relationship of emotions
      and emotional behavioral factors to the development of hypertension in children.
      Using the Roy Adaptation Model as a guide, this study investigated the
      relationship of anger expression and blood pressure (BP) among adolescents 16-18
      years of age. Participants were 63 urban high school seniors. Measurements
      included the Anger Expression Inventory, a Demographic Questionnaire, and
      measures of systolic and diastolic blood pressure. Analysis revealed significant
      positive relationships between anger expression with blood pressure, and a
      significant inverse relationship between blood pressure and the control of anger
      for girls. No significant relationships between anger expression and blood
      pressure were noted for boys. The majority of students (53%) were found to have
      high normal or hypertensive blood pressure readings, putting them at increased
      cardiovascular risk.

PMID- 15560732
TI  - The health of children in foster care.
AB  - This qualitative study of school nurses describes what the nurses want to do for
      school children in foster care, what they are actually doing, and how the school
      organization affects the provision of care. The study looked at the nurses'
      practice through the lens of the Social Ecological Model of Health, identified
      interventions using the Minnesota Public Health Intervention Model, and analyzed
      the school organization using the Bolman-Deal Model (Bolman & Deal, 1997). A
      purposive sample of nurses was chosen to participate in interviews, and
      observations of their work and a survey on the frequency of their interventions
      was implemented. Interviews were analyzed using a phenomenological approach. Four
      themes derived from the data included structural barriers to client access,
      nonrecognition of the broad determinants of health, isolationism, and lack of
      political power. School nurses are aware of foster children's increased health
      care needs, yet increased services are not provided as a result of a lack of
      organizational support.

PMID- 15560733
TI  - The effects of budget, delegation, and other variables on the future of school
      nursing.
AB  - The purpose of this exploratory research study was to survey Kansas school nurses
      to determine the impact of budget, delegation, and other variables on the future
      of school nursing. Issues of education and certification status, educational
      budget, delegation, school nurse-to-student ratio, number of school buildings
      assigned, Metropolitan Statistical Area, and years of school nursing experience
      were also investigated. The Budget Impact School Nurse Questionnaire online
      survey was used to gather data. Findings revealed that school nurses were well
      prepared academically, but that many school nurses lacked certification. The use
      of UAPs and the future of school nursing were significantly affected by budget
      constraints, delegation, number of buildings assigned, legislative contact, and
      Metropolitan Statistical Area (urban location). Education in delegation and years
      of experience as a school nurse significantly affected opportunities for health
      education. The findings depicted budget, school nurse staffing, delegation, and
      geographic areas as the main variables that have an impact on school nursing.

PMID- 15560734
TI  - Chiari Type 1 malformation and upper airway obstruction in adolescents.

PMID- 15560735
TI  - Lumps, bumps, and things that go itch in your office!

PMID- 15560736
TI  - Unexpected photolysis of the sunscreen octinoxate in the presence of the
      sunscreen avobenzone.
AB  - A major concern raised about photostability studies of sunscreen products is that
      the photodegradation of sunscreens does not readily translate into changes in
      product performance. This study examines the correlation between photochemical
      degradation of sunscreen agents and changes in protection provided by sunscreen
      films. Films of a commercial sunscreen product containing avobenzone, oxybenzone
      and octinoxate were irradiated using a fluorescent UV-A phototherapy lamp with
      additional UV-B blocking filter. Periodically, during irradiation the
      transmittances of the films were measured and samples collected for chemical
      analysis of the sunscreen agents using high-performance liquid chromatography
      techniques. The results show that UV-induced changes in UV transmittance of
      sunscreen films correlate with changes in concentration of sunscreen agents. In a
      parallel experiment, we also irradiated a thin film of the same product in the
      cavity of an electron spin resonance (ESR) spectrometer. We report the
      concomitant photolysis of avobenzone and octinoxate that predominates over
      expected E/Z photoisomerization and that irradiation of a film of this product
      produced free radicals detected by ESR spectroscopy that persisted even after
      exposure had ended.

PMID- 15560737
TI  - In vivo optical analysis of quantitative changes in collagen and elastin during
      arterial remodeling.
AB  - Altered collagen and elastin content correlates closely with remodeling of the
      arterial wall after injury. Optical analytical approaches have been shown to
      detect qualitative changes in plaque composition, but the capacity for detection
      of quantitative changes in arterial collagen and elastin content in vivo is not
      known. We have assessed fluorescence spectroscopy for detection of quantitative
      changes in arterial composition in situ, in rabbit models of angioplasty and
      stent implant. Fluorescence emission intensity (FEI) recorded at sites remote
      from the primary implant site was correlated with immunohistochemical (IH)
      analysis and extracted elastin and collagen. FEI was significantly decreased
      (P<0.05) after treatment with anti-inflammatory agents, and plaque area decreased
      on comparison with saline-treated rabbits after stent implant or angioplasty
      (P<or=0.013). Excellent correlations for FEI with elastin and collagen I, III and
      IV content measured by IH (R2>or=0.961) analysis were detected by multiple
      regression (MR) analysis. Good correlations also were found for FEI with elastin
      and collagen measured by high-performance liquid chromatography; MR analysis
      provided highly predictive values for collagen and elastin (R2>or=0.994).
      Fluorescence spectroscopic analysis detects quantitative compositional changes in
      arterial connective tissue in vivo, demonstrating changes at sites remote from
      primary angioplasty and stent implant sites.

PMID- 15560738
TI  - Alterations in mitochondrial and apoptosis-regulating gene expression in
      photodynamic therapy-resistant variants of HT29 colon carcinoma cells.
AB  - Photodynamic therapy (PDT) is a novel cancer therapy inducing irreversible
      photodamage to tumor tissue via photosensitizer-mediated oxidative cytotoxicity.
      The cellular and molecular responses associated with PDT are only partially
      understood. We have reported previously the generation of several photosensitizer
      specific PDT-resistant cell variants of HT29 human colon adenocarcinoma cells by
      selecting cells from sequential PDT treatment using different photosensitizers.
      In this report, we describe the use of messenger RNA (mRNA) differential display
      to identify genes that were differentially expressed in the parental HT29 cells
      compared with their resistant variants. In comparison with parental HT29 cells,
      mRNA expression was increased in the PDT-resistant cell variants for BNIP3,
      estrogen receptor-binding fragment-associated gene 9, Myh-1c, cytoplasmic dynein
      light chain 1, small membrane protein I and differential dependent protein. In
      contrast, expression in the PDT-resistant variants was downregulated for NNX3,
      human HepG2 3' region Mbol complementary DNA, glutamate dehydrogenase, hepatoma
      derived growth factor and the mitochondrial genes coding for 16S ribosomal RNA
      (rRNA) and nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 4. The
      reduction for mitochondrial 16S rRNA in the PDT-resistant variants was confirmed
      by Northern blotting, and the elevated expression of the proapoptotic BNIP3 in
      the PDT-resistant variants was confirmed by Northern and Western blotting
      analysis. We also examined the expression of some additional apoptosis-regulating
      genes using Western blotting. We show an increased expression of Bcl-2 and heat
      shock protein 27 and a downregulation of Bax in the PDT-resistant variants. In
      addition, the mutant p53 levels in the parental HT29 cells were reduced
      substantially in the PDT-resistant variants. We suggest that the altered
      expression in several mitochondrial and apoptosis-regulating genes contributes to
      PDT resistance.

PMID- 15560739
TI  - Photoreactions of 1,4-Naphthoquinones: effects of substituents and water on the
      intermediates and reactivity.
AB  - The photochemistry of lapachol and other 1,4-naphthoquinone (NQ) derivatives,
      e.g. 2-methoxy-1,4-naphthoquinone (MeONQ), 2-hydroxy-1,4-naphthoquinone (2-HONQ)
      or 5-hydroxy-1,4-naphthoquinone (5-HONQ) and 2-methyl-5-hydroxy-1,4
      naphthoquinone (P-NQ) in solution at room temperature was studied by ultraviolet
      visible spectroscopy after nanosecond laser pulses at 248 nm. The triplet state
      and semiquinone radicals were observed for MeONQ, HONQ and P-NQ, whereas for
      lapachol, intramolecular H-atom and charge transfer processes take place, as in
      the case of vitamin K1. The photoinduced reaction of NQ into HONQ is initiated by
      nucleophilic water addition to the triplet state, and for the secondary
      reactions, a modified mechanism is proposed.

PMID- 15560740
TI  - Molecular beacon probes of photodamage in thymine and uracil oligonucleotides.
AB  - Molecular beacons (MB) are becoming more common as sequence-selective detectors
      of nucleic acids. Although they can easily detect single-base mismatches, they
      have never been used to directly detect DNA or RNA damage. To measure the degree
      of ultraviolet (UV) light damage in oligonucleotides, we report a novel MB
      approach for general detection of photoproducts in UV-irradiated rU17 and dT17
      oligonucleotides. With monochromatic UV light irradiation at ca 280 nm under
      anoxic conditions, the oligonucleotide absorption decays with a single
      exponential time constant of 123+/-1 min for rU17 and with double-exponential
      time constants of 78+/-0.5 min (99%) and 180+/-5 min (0.05%) for dT17
      oligonucleotides. Under the same conditions, the MB fluorescence decays more
      quickly, with single-exponential time constants of 19+/-2 and 26+/-3 min for rU17
      and dT17, respectively. Similar kinetics were observed with broadband UV light
      irradiation of oligonucleotides. The differences in the UV damage kinetics of
      dT17 and rU17 and their detection by absorption and fluorescence techniques will
      be discussed in the context of differential instabilities introduced in the
      nucleic acid-MB duplex by the different photoproducts formed.

PMID- 15560741
TI  - Stability of tin etiopurpurin.
AB  - Formulations of the tin etiopurpurin (SnET2) have been observed to undergo a
      spectral change on storage in dimethylformamide solution. This results in an
      alteration in the action spectrum, with enhanced photodynamic activity at lower
      wavelengths and decreased activity at 660 nm. On the basis of structural
      considerations, a reduced analog of SnET2 was prepared with an absorbance maximum
      at 640 nm. Formation of this product, termed SnET2H(2) relieves steric strain
      inherent in the parent molecule. Nuclear magnetic resonance, spectral and
      photodynamic data are consistent with the formation of SnET2H(2) during SnET2
      storage. Slight modifications in the original synthesis are also reported,
      resulting in improved yields of intermediate products.

PMID- 15560744
TI  - The future of non-human primates as laboratory animals in Great Britain: please
      don't build the Cambridge laboratory!

PMID- 15560745
TI  - A two-centre evaluation of the human organotypic skin explant culture model for
      screening contact allergens.
AB  - Animal models are considered to be the "gold standard" for determining the
      potential contact allergenicity of low molecular weight chemicals. However,
      governmental regulations and ethical considerations limit the use of animals for
      such purposes. There is therefore a need for in vitro alternative models. The
      human organotypic skin explant culture (HOSEC) model is reported to be a
      promising alternative method for the predictive testing of contact allergens. The
      accelerated migration of Langerhans cells from the epidermis upon exposure to
      contact allergens is used to identify chemicals that are potentially capable of
      inducing a delayed-type hypersensitivity. In the study described in this paper,
      the model was further refined, and used, in two independent laboratories, to
      screen 23 low molecular weight compounds of known classification for their
      allergenicity. Each laboratory was able to accurately detect the contact
      allergens, despite small variations in the protocols used. However, the
      classification of dermal irritants, which have often been falsely classified as
      allergens, varied between the two laboratories. Despite the current limitations
      of the HOSEC model, the accuracy of the predictions made (sensitiser or non
      sensitiser) compare favourably with classifications obtained with commonly used
      animal models. The HOSEC model has the potential to be developed further as an in
      vitro alternative to animal models for screening for contact allergens.

PMID- 15560746
TI  - Cryopreservation of organotypic brain spheroid cultures.
AB  - The cryopreservation of hen and rat brain spheroids was investigated. Brain
      spheroid cultures were prepared from 7-day-old hen embryos or 16-day-old rat
      embryos, by using a rotation-mediated culture system. The spheroids were
      cryopreserved in medium containing 5-15% dimethyl sulphoxide (DMSO) and stored in
      liquid nitrogen, by using a two-stage cooling procedure. The results show that
      the viability, as indicated by the total protein content of hen embryo brain
      spheroids at 24 hours, and at 3, 7 and 28 days after thawing, ranged from 45.5%
      to 64.2% of control values. It took 3 days for the post-thaw brain spheroids to
      stabilise, as indicated by their morphology and selected neural markers of
      functionality. These functions were maintained over a 28-day observation period.
      Spheroids cultured for 12-15 days in vitro before cryopreservation survived
      better than those that were cryopreserved after 5-7 days in vitro. The viability
      and biochemical functionality of spheroids after long-term (up to 6 months)
      storage were similar to those following short-term storage. The viability of rat
      brain spheroids cryopreserved in 15% DMSO, as indicated by total protein content,
      at 24 hours, and at 3 or 7 days after thawing, ranged from 23.1% to 32.1% of
      control values. This study shows for the first time that brain spheroids prepared
      from primary tissue can be successfully cryopreserved.

PMID- 15560747
TI  - Microarray assessment of fibronectin, collagen and integrin expression and the
      role of fibronectin-collagen coating in the growth of normal, SV40 T-antigen
      immortalised and malignant human oral keratinocytes.
AB  - Extracellular matrix proteins affect the growth and survival of epithelial
      tissues. Accordingly, surface coating with fibronectin and collagen is a common
      practice for promoting keratinocyte culture. In this study, the expression of
      fibronectin and collagen-related factors, including integrins, by normal (NOK),
      SV40 T-antigen-immortalised (SVpgC2a) and malignant (SqCC/Y1) human oral
      keratinocytes, under standardised, serum-free conditions, was investigated by
      using microarray analysis. Cell growth was also studied in the presence and
      absence of a matrix consisting of human fibronectin and bovine collagen type I
      (FN-COL). Fibronectin transcripts were abundant in all cells, whereas 16 of 29
      collagen chains and 14 of 24 integrin subunits were variably detected. With
      regard to both the expression level and the number of transcripts, higher
      collagen and lower integrin expression was observed in SVpgC2a cells than in NOKs
      and SqCC/Y1 cells. The cell types differed with regard to colony-forming
      efficiency and the rate and kinetics of growth at high cell density. For all cell
      types, FN-COL coating consistently stimulated cell migration, without influencing
      growth in mass culture or clonal density. The results demonstrate the
      transcription of genes associated with the formation and function of fibronectin
      and collagen in oral epithelium, and variably altered expression patterns in
      transformed states, and show that keratinocyte lines can be successfully
      transferred without the stimulus from extracellular FN-COL.

PMID- 15560748
TI  - Carbaryl-induced behavioural and reproductive abnormalities in the earthworm
      Metaphire posthuma: a sensitive model.
AB  - Carbaryl, an N-methyl carbamate insecticide, is used in India to control foliar
      insects, but, due to soil contamination, it also adversely affects non-target
      organisms such as earthworms. This paper deals with the toxic effects of carbaryl
      on the behavioural and reproductive profiles of the earthworm, Metaphire
      posthuma. Locomotion and geotaxis were significantly affected, even after a 20
      minute exposure to 0.125ppm carbaryl. The hatching of cocoons was altered at
      0.5ppm, whereas cocoon production was retarded even at 0.125ppm carbaryl. No
      cocoon production was observed at 2.0ppm carbaryl. Sperm head abnormalities were
      reported even at the lowest test concentration of 0.125ppm. Wavy head
      abnormalities were observed at 0.125ppm carbaryl, whereas at 0.25ppm and 0.5ppm,
      the sperm heads became amorphous and the head nucleus was turned into granules
      deposited within the wavy head. It is concluded that the earthworm could be used
      as an ecosystem model for the initial toxicity testing of environmental
      pollutants.

PMID- 15560749
TI  - The mouse bioassay for diarrhetic shellfish poisoning: a gross misuse of
      laboratory animals and of scientific methodology.
AB  - The UK shellfish industry has recently been affected by the statutory closure of
      several cockle beds, following the detection of samples causing rapid and severe
      reactions in the regulatory approved test for diarrhetic shellfish poisoning
      (DSP) toxins, the mouse bioassay (MBA). It is contended that these so-called
      atypical results are due to procedural artefacts of the MBA; so far, several
      studies have failed to identify their cause. This paper critically assesses the
      development, regulatory use and methodological deficiencies of the MBA. It also
      discusses how testing for DSP toxins could and should have been improved and made
      more humane by applying the Three Rs concept of Reduction, Refinement and
      Replacement, and by the proper validation of the test method used. It is
      concluded that the MBA should not have been developed for the routine screening
      of shellfish samples, as it has a substantially severe endpoint and is not used
      as part of a tiered-testing strategy with non-animal methods. Moreover, during
      the UK monitoring programme for DSP toxins, the assay has been used without an
      optimised and universal protocol, and apparently without due regard to the
      principles of basic scientific methodology. In view of this, the atypical results
      obtained for cockle samples cannot be relied on as evidence of a human health
      hazard. It is recommended that the use of the MBA should be discontinued as soon
      as possible, in favour of other methods, especially those involving non-animal
      techniques. In the short-term, these methods should be based on analytical
      chemical detection systems and the essential availability of the relevant pure
      toxin standards. The lack of any known toxins in samples should be taken as
      evidence of lack of contamination. The suitability of the existing non-animal
      methods needs to be assessed as a matter of urgency. It is crucial that all new
      methods should be properly validated, and that their acceptability for their
      stated purposes should be endorsed by recognised criteria and validation centres,
      before being recommended to, or required by, regulatory agencies. In this way,
      the possibility that scientifically unsuitable methods will once again be used
      for monitoring for the contamination of shellfish with toxins can be avoided.
      This gross misuse of laboratory animals and ill-judged application of science
      should never be allowed to occur again.

PMID- 15560750
TI  - Botulinum toxin testing in animals: the questions remain unanswered.
AB  - Questions are raised concerning the testing of botulinum toxin in animals, and
      the British Government's answers to Parliamentary Questions on this issue are
      reviewed, with an emphasis on the potential for reducing, refining and replacing
      the animal tests, which can involve substantial severity, and on the
      responsibility of the Home Office so see that the Three Rs approach is fully
      applied in this specific case.

PMID- 15560751
TI  - Mode of action of xylogalacturonan hydrolase towards xylogalacturonan and
      xylogalacturonan oligosaccharides.
AB  - XGH (xylogalacturonan hydrolase; GH 28) is an enzyme that is capable of degrading
      XGA (xylogalacturonan), which is a polymer of alpha-D-galacturonic acid, highly
      substituted with beta-D-xylose. XGA is present in cell walls of various plants
      and exudates, such as gum tragacanth. XGA oligosaccharides were derived from an
      XGH digestion of gum tragacanth, then fractionated, and analysed for their sugar
      composition and structure by matrix-assisted laser-desorption ionization-time-of
      flight MS and nanospray MS. Several oligosaccharides from XGA were identified
      with different galacturonic acid/xylose ratios including five oligosaccharide
      isomers. Although XGH can act as an endo-enzyme, product-progression profiling
      showed that the disaccharide GalAXyl was predominantly produced from XGA by XGH,
      which indicated also an exolytic action. The latter was further supported by
      degradation studies of purified oligosaccharide GalA4Xyl3. It was shown that XGH
      acted from the non-reducing end towards the reducing end of this oligosaccharide,
      and showed the processive character of XGH. The results from this study further
      show that although XGH prefers to act between two xylosidated GalA units, it
      tolerates unsubstituted GalA units in its -1 and +1 subsites.

PMID- 15560752
TI  - Cleavage at the stem region releases an active ectodomain of the membrane type 1
      matrix metalloproteinase.
AB  - MT1-MMP (membrane type 1 matrix metalloproteinase) is a membrane-anchored MMP
      that can be shed to the extracellular milieu. In the present study we report the
      primary structure and activity of the major soluble form of MT1-MMP. MS analysis
      of the purified 50-kDa soluble MT1-MMP form shows that the enzyme extends from
      Tyr112 to Val524, indicating that formation of this species requires a
      proteolytic cleavage within the stem region. In agreement, deletion of the entire
      stem region of MT1-MMP inhibited shedding of the 50-kDa species. A recombinant 50
      kDa species (Tyr112-Val524) expressed in cells exhibited enzymatic activity
      against pro-MMP-2 and galectin-3, and thus this species is a competent protease.
      The recombinant 50-kDa soluble form also decreased the level of surface
      associated TIMP-2 (tissue inhibitor of metalloproteinase 2) when administered to
      cells expressing wild-type membrane-anchored MT1-MMP, suggesting that ectodomain
      shedding of MT1-MMP can alter the MMP/TIMP balance on the cell surface. A
      approximately 53-kDa species of MT1-MMP was also isolated from a non-detergent
      extract of human breast carcinoma tissue and was found to lack the cytosolic
      tail, as determined with specific MT1-MMP domain antibodies. Together, these data
      show that MT1-MMP ectodomain shedding is a physiological process that may broaden
      MT1-MMP activity to the pericellular space.

PMID- 15560753
TI  - Inositol phosphoceramide synthase is a regulator of intracellular levels of
      diacylglycerol and ceramide during the G1 to S transition in Saccharomyces
      cerevisiae.
AB  - We recently reported that DAG (diacylglycerol) generated during sphingomyelin
      synthesis plays an important role in protein kinase C activation and cell
      proliferation in Madin-Darby canine kidney cells [Cerbon and Lopez-Sanchez (2003)
      Biochem. J. 373, 917-924]. In yeast cells, IPC (inositol phosphoceramide)
      synthase catalyses the transfer of phosphoinositol from phosphatidylinositol to
      ceramide to form IPC and generates DAG. In the present study, we found that,
      during the G1 to S transition after N2-starvation, there was a significant
      increase in the synthesis of IPC accompanied by a progressive increase (up to 6
      fold) in the level of DAG. The increased DAG levels coincided with decrements in
      ceramide and sphingoid base levels, conditions that are adequate for the
      activation of putative protein kinase C required for the G1 to S transition and
      proliferation of yeast cells. To separate the role of DAG generated during IPC
      synthesis from that originating from other sources, we utilized beta
      chloroalanine and myriocin, inhibitors of serine:palmitoyl-CoA transferase, the
      first committed step in sphingolipid synthesis, to avoid accumulation of
      sphingolipid intermediates. When the synthesis of sphingolipids was inhibited,
      DAG accumulation was significantly decreased and the G1 to S transition was
      blocked; such blockage was avoided by metabolic complementation with
      phytosphingosine. The DAG/ceramide ratio was 0.27 and it changed to 2.0 during
      growth re-initiation, suggesting that the synthesis of phosphosphingolipids could
      act to switch growth arrest (increased ceramide) to a mitogenic signal (increased
      DAG), and that this signalling process is preserved in yeast and mammalian cells.

PMID- 15560754
TI  - Peptide mimotopes of Mycobacterium tuberculosis carbohydrate immunodeterminants.
AB  - Cell-surface saccharides of Mycobacterium tuberculosis appear to be crucial
      factors in tuberculosis pathogenicity and could be useful antigens in
      tuberculosis immunodiagnosis. In the present study, we report the successful
      antigenic and immunogenic mimicry of mannose-containing cell-wall compounds of M.
      tuberculosis by dodecamer peptides identified by phage-display technology. Using
      a rabbit antiserum raised against M. tuberculosis cell-surface saccharides as a
      target for biopanning, peptides with three different consensus sequences were
      identified. Phage-displayed and chemically synthesized peptides bound to the
      anticarbohydrate antiserum. Rabbit antibodies elicited against the peptide
      QEPLMGTVPIRAGGGS recognize the mannosylated M. tuberculosis cell-wall antigens
      arabinomannan and lipoarabinomannan, and the glycosylated recombinant protein
      alanine/proline-rich antigen. Furthermore, antibodies were also able to react
      with mannan from Saccharomyces cerevisiae, but not with phosphatidylinositol
      dimannosides or arabinogalactan from mycobacteria. These results suggest that the
      immunogenic peptide mimics oligomannosidic epitopes. Interestingly, this report
      provides evidence that, in contrast with previously known carbohydrate mimotopes,
      no aromatic residues are necessary in a peptide sequence for mimicking unusual
      glycoconjugates synthesized by mycobacteria. The possible usefulness of the
      identified peptide mimotopes as surrogate reagents for immunodiagnosis and for
      the study of functional roles of the native non-peptide epitopes is discussed.

PMID- 15560755
TI  - Pimecrolimus -- an anti-inflammatory drug targeting the skin.
AB  - Pimecrolimus is the most recent member of calcineurin inhibitors available for
      the therapy for inflammatory skin diseases. It targets T-cells and mast cells and
      inhibits the production and release of cytokines and other inflammatory
      mediators, as well as the expression of signals essential for the activation of
      inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In
      contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic
      cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in
      vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro
      with human skin and by comparison of clinical pharmacokinetic data from patients
      with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus
      and much less than corticosteroids. It, thus, has a lower potential for
      transcutaneous resorption after topical administration, resulting in a lower risk
      of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal
      models of skin inflammation, including a model reflecting neurogenic
      inflammation, but a more favourable balance of anti-inflammatory vs.
      immunosuppressive activity than tacrolimus. Pimecrolimus does not affect
      sensitization in a murine model of allergic contact dermatitis and has a lower
      potency in various models of immunosuppression after systemic administration,
      compared to tacrolimus. In conclusion, the results of preclinical studies show
      that pimecrolimus has a selective pharmacological profile, suited for effective
      and safe treatment for inflammatory skin diseases.

PMID- 15560756
TI  - The macrophage-activating lipopeptide-2 accelerates wound healing in diabetic
      mice.
AB  - Wound healing in healthy individuals proceeds at an optimal rate. However, in
      patients, with -- e.g.-- locally impaired blood flow or diabetes, chronic wounds
      develop and often become infected. Chronic wounds mean a low quality of life for
      the afflicted patients, not to mention enormous costs. Rather than using
      recombinant growth factors to accelerate wound healing, we employed the toll-like
      receptor agonist macrophage-activating lipopeptide-2 (MALP-2) to improve the
      healing of full-thickness excision skin wounds in an animal model with obese,
      diabetic mice. A gene array experiment suggested that MALP-2 stimulates the
      release of various mediators involved in wound healing. Further data to be
      presented in this study will show (i) that MALP-2 is capable of stimulating the
      appearance of the monocyte chemoattractant protein-1 at the wound site, (ii) that
      this leads to increased leucocyte and, in particular, macrophage infiltration and
      (iii) that MALP-2-treated wounds closed 2 weeks earlier than vehicle-treated
      controls. MALP-2, thus, appears to stimulate the early inflammatory process
      needed to set in motion the ensuing consecutive natural steps of wound healing
      resulting in wound closure.

PMID- 15560757
TI  - The maturation-dependent production of interleukin-16 is impaired in monocyte
      derived dendritic cells from atopic dermatitis patients but is restored by
      inflammatory cytokines TNF-alpha and IL-1beta.
AB  - BACKGROUND: Maturation of dendritic cells (DCs) influences important DC functions
      such as production of cytokines. Recently, DCs were identified as a source of
      interleukin-16 (IL-16), a chemotactic factor for DCs themselves, CD4+ T cells,
      and eosinophils. There is evidence that DC-derived IL-16 may contribute to the
      pathogenesis of atopic dermatitis (AD). OBJECTIVE: To investigate the production
      of IL-16 during differentiation of monocytes into DCs in healthy individuals and
      patients with AD. METHODS: IL-16 production was investigated by quantitative real
      time RT-PCR, intracellular cytokine staining, immunoblotting, and ELISA. RESULTS:
      DCs generated from peripheral monocytes by 5-day culture in the presence of IL-4
      and granulocyte/macrophage colony-stimulating factor acquired the capability to
      synthesize, store, and secrete IL-16. Storage and release of IL-16 was further
      enhanced during final DC maturation induced by additional 3-day culture with
      tumor necrosis factor-alpha (TNF-alpha) and monocyte-conditioned medium.
      Maturation, as determined by up-regulation of CD83 and CD86 surface expression,
      and production of IL-16, but not production of IL-10 and IL-12p40 was impaired in
      day 8 DCs derived from AD patients compared to those from healthy donors.
      Stimulation of day 8 DCs from AD patients with TNF-alpha and IL-1beta enhanced
      the expression of CD83 and CD86 and restored the production of IL-16.
      CONCLUSIONS: Signals involved in the activation and maturation of DCs enhance
      their capacity to produce IL-16. Functional abnormalities present in patients
      with AD at the monocyte level may account for impaired maturation and IL-16
      production of monocyte-derived DCs.

PMID- 15560758
TI  - Alpha-MSH reduces the internalization of Staphylococcus aureus and down-regulates
      HSP 70, integrins and cytokine expression in human keratinocyte cell lines.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide predominantly
      produced by the pituitary gland, but it is also generated by many extra-pituitary
      cells including keratinocytes of the skin. This neuropeptide has anti
      inflammatory and antimicrobial effects and probably contributes in innate
      immunity. Staphylococcus aureus is the aetiological agent of a wide range of
      infections in humans. Colonization of human skin by S. aureus is a characteristic
      feature of several skin diseases and is often followed by tissue invasion and
      severe cell damage. The aim of our study was to detect a possible role of alpha
      MSH during the early infection stages in the adhesion and penetration of
      keratinocytes before cell damage. Our data demonstrated that alpha-MSH
      precociously down-regulates the production of integrins such as beta1 and heat
      shock surface protein 70, essential molecules for the entry of S. aureus.
      Moreover, in our experimental model, alpha-MSH induces the down-regulation of the
      pro-inflammatory cytokine expression and of the adhesion molecules in
      keratinocytes activated by S. aureus. Our data suggest that alpha-MSH plays a
      protective role in the skin by reducing infection and the inflammatory process.

PMID- 15560759
TI  - Narrow-band ultraviolet-B stimulates proliferation and migration of cultured
      melanocytes.
AB  - Narrow-band ultraviolet-B (UVB) radiation is an effective treatment for vitiligo
      vulgaris. However, the mechanisms of narrow-band UVB in inducing repigmentation
      of vitiligo lesions are not thoroughly clarified. The purpose of our study was to
      investigate the effects of narrow-band UVB irradiation on melanocyte
      proliferation and migration in vitro. Our results showed that the cell counts as
      well as [3H]thymidine uptake of melanocytes were significantly enhanced by narrow
      band UVB-irradiated keratinocyte supernatants. In these supernatants, a
      significant increase in basic fibroblast growth factor (bFGF) and in endothelin-1
      (ET-1) release was observed. bFGF is a natural mitogen for melanocytes, whereas
      ET-1 can stimulate DNA synthesis in melanocytes. This stimulatory effect of
      melanocyte proliferation by supernatants derived from narrow-band UVB-irradiated
      keratinocytes was significantly reduced by a selective endothelin-B (ET-B)
      receptor antagonist (BQ788), suggesting an essential role of ET-1 on melanocyte
      proliferation. Our results of time-lapse microphotography revealed a stimulatory
      effect of narrow-band UVB irradiation on melanocyte migration. Focal adhesion
      kinase (FAK) plays a pivotal role in cell migration. Phosphorylated FAK
      (p125(FAK)) expression on melanocyte was enhanced by narrow-band UVB irradiation.
      In this study, narrow-band UVB irradiation stimulated a significant increase in
      matrix metalloproteinase-2 (MMP-2) activity in melanocyte supernatants. Narrow
      band UVB-irradiation-induced migration of melanocytes was significantly
      annihilated by the addition of p125(FAK) inhibitor (herbimycin-A) or MMP-2
      inhibitor (GM6001). These results suggest that p125(FAK) and MMP-2 activity play
      important roles in narrow-band UVB-induced migration of melanocytes. Our results
      provide a theoretical basis for the effectiveness of narrow-band UVB irradiation
      in treating vitiligo.

PMID- 15560760
TI  - Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band
      UVB therapy is accompanied by a decrease in the expression of IFN-gamma inducers 
      - IL-12, IL-18 and IL-23.
AB  - Type-1 cytokine-producing T cells are important in the pathogenesis of psoriasis
      vulgaris, for which efficient therapy is provided by means of narrow-band
      ultraviolet-B (NB-UVB). The expression of the type-1 cytokine interferon-gamma
      (IFN-gamma) is regulated by interleukin-12 (IL-12), IL-15, IL-18 and IL-23;
      however, not much is known about the effect of this therapy on the levels of
      these cytokines in lesional psoriatic skin in situ. In this study, we
      investigated the effects of NB-UVB therapy on the expression of IFN-gamma
      inducing cytokines. Ten patients with chronic plaque-type psoriasis selected to
      be treated with NB-UVB therapy were recruited for these experiments and the
      expression of cytokines IL-12, IL-15, IL-18, IL-23 and IFN-gamma in lesional
      psoriatic skin before, during and after therapy was determined with the help of
      immunohistochemistry. Double staining was performed in order to determine the
      cell types expressing these cytokines. The decrease in the psoriasis area and
      severity index was accompanied by a significant decrease in the expression of IFN
      gamma, and concomitantly, significant reduction of IFN-gamma inducers -- IL-12,
      IL-18 and IL-23. Thus, we concluded that the decrease of IFN-gamma expression in
      psoriasis lesions after NB-UVB therapy could be a result of diminished expression
      of IL-12, IL-18 and IL-23 in lesional skin. Therapies targeting these three
      cytokines should, therefore, be considered in the treatment of psoriasis.

PMID- 15560761
TI  - Transcriptional regulation of the 230-kDa bullous pemphigoid antigen gene
      expression by interferon regulatory factor 1 and interferon regulatory factor 2
      in normal human epidermal keratinocytes.
AB  - Interferon regulatory factors (IRFs) are a family of transcriptional factors
      induced by interferon-gamma (IFN-gamma). Recent studies have indicated that the
      deregulation of IRF system in keratinocytes is responsible, at least in part, for
      aberrant proliferation and the differentiation of the psoriatic epidermis.
      Previously, we reported that the expression of 230-kDa bullous pemphigoid antigen
      (BPAG1) gene, which is strictly restricted to basal keratinocytes, is
      transcriptionally suppressed by IFN-gamma, but the contribution of IRFs in such
      suppression is still unclear. In this study, we investigated the role of IRFs in
      the regulation of BPAG1 gene expression. Computer analysis identified IRF1 and
      IRF2 consensus sequences between -135 and -123 on BPAG1 promoter region.
      Transient transfection studies with BPAG1 promoter-luciferase reporter gene
      plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2
      directly down-regulated BPAG1 gene transcription in cultured normal human
      epidermal keratinocytes. Several sets of gel retardation assays with the BPAG1
      IRF binding sequence as a probe indicated that IRF1 and IRF2 could bind to the
      BPAG1-IRF sequence, but some other protein(s), which was induced by IFN-gamma
      stimulation and possessed binding activity to IRF consensus sequence, showed
      preferential binding to the BPAG1-IRF sequence. Our results suggest that IFN
      gamma-IRF system is involved in BPAG1 gene regulation in type-1 helper T-cell
      inflammatory skin conditions, such as psoriasis vulgaris.

PMID- 15560762
TI  - Topical glucocorticoid augments scratching behaviour in dinitrofluorobenzene
      sensitized mice by the induction of substance P.
AB  - Topical glucocorticoid (GC) is commonly applied in atopic dermatitis treatment.
      However, the chronic use of GC may be associated with significant side effects.
      In this study, we investigated whether long-term epicutaneous application of GC
      modulates scratching behaviour in dinitrofluorobenzene (DNFB) contact-sensitized
      mice. After challenge with DNFB, scratching behaviour was increased in DNFB
      sensitized mice treated with GC in contrast to control mice. In addition, reverse
      transcriptase-polymerase chain reaction analysis demonstrated that the expression
      of preprotachykinin-A (PPT-A) mRNA, a precursor of substance P (SP), and
      inducible nitric oxide synthase (iNOS) mRNA in mice, to which GC was applied, was
      only observed. In order to evaluate the factors responsible for the augmented
      scratching behaviour, we injected various cytokines (interleukin-1alpha (IL
      1alpha), IL-2, IL-3 and tumour necrosis factor-alpha (TNF-alpha)) subcutaneously
      into the ear of DNFB contact-sensitized mice before DNFB challenge. Among the
      cytokines, only IL-3 and TNF-alpha significantly increased scratching behaviour
      in DNFB contact dermatitis mice. Furthermore, PPT-A mRNA was only expressed in
      mice pre-injected with IL-3 before challenge, but not in those pre-injected with
      other cytokines. Taken together, our results suggest that topical GC may augment
      the itching sensation in DNFB-sensitized mice through modulation of iNOS and SP
      induced by IL-3.

PMID- 15560763
TI  - The effects of sleep debt and monotonous work on sleepiness and performance
      during a 12-h dayshift.
AB  - The study examined the effects of the amount of preceding sleep and work pace on
      sleepiness and cognitive performance during a 12-h dayshift. Twelve process
      operators (aged 28-56 years) completed a study with four single 12-h dayshifts
      and preceding night sleep in the laboratory. A simulated distillation process
      served as a work task. The 12-h shifts differed from each other in terms of the
      amount of preceding night sleep (23:00-06:30 hours or 2:30-6:30 hours) and work
      pace (slow or fast). All shifts contained four work simulation sessions of 1.5 h,
      and each of them included a 15-min alarm session. Cognitive performance was also
      measured with a 10-choice reaction time test and a mental subtraction test.
      Objective sleepiness was measured with a continuous
      electroencephalography/electro-oculography (EEG/EOG) recording during the work
      periods and with a sleep latency test. Subjective sleepiness at work was measured
      with the Karolinska Sleepiness Scale. Sleep debt increased the proportion of
      EEG/EOG-defined and subjective sleepiness at work, but did not impair work or
      test performance. The fatiguing effect of monotonous work as indicated by EEG/EOG
      defined sleepiness was comparable with the effect of sleep debt. The alarm epochs
      in the middle of monotonous work temporarily decreased EEG/EOG-defined
      sleepiness. Sleep debt or monotonous work did not have a significant effect on
      the results of the sleep latency test. None of the sleepiness or performance
      measures indicated the impairment of a subject's functional capacity at the end
      of the 12-h shift. Our results suggest that monotonous work is at least as
      harmful as moderate sleep debt for alertness at work. The results support the
      view that the last hours of a single 12-h dayshift with frequent pauses are not
      associated with an increase in sleepiness or performance errors.

PMID- 15560764
TI  - Effect of cognitive arousal on sleep latency, somatic and cortical arousal
      following partial sleep deprivation.
AB  - Emerging research has shown that sleepiness, defined as the tendency to fall
      asleep, is not only determined by sleep pressure and time of day, but also by
      physiological and cognitive arousal. In this study we evaluated (i) the impact of
      experimentally induced cognitive arousal on electroencephalogram (EEG) defined
      sleep latency, and subjective, somatic and cortical arousal, and (ii) whether
      experimentally induced cognitive arousal enhances performance on a driving
      simulator test. Twelve healthy sleepers each spent three nights and the following
      day in the sleep laboratory: an adaptation, a cognitive arousal and a neutral
      testing day. In the cognitive arousal condition, a visit of a television camera
      crew took place and subjects were asked to be interviewed. On each testing day, a
      5-min heart rate recording, subjective sleepiness and arousal scales, Multiple
      Sleep Latency Test and a 25-min driving simulator task were scheduled three times
      at 2-h intervals. Experimentally induced cognitive arousal resulted in
      significant increases in objective sleep latency. Significantly elevated levels
      of subjective and somatic arousal--as indexed by a subjective arousal scale and
      heart rate--were also evidenced following cognitive arousal induction. A
      marginally significant trend for increased cortical arousal, measured by EEG beta
      activity, was also found. No effects were found on driving simulator performance.
      These findings support the concept of cognitive arousal as a significant
      component in determining sleep latency. In addition, it was illustrated that
      cognitively induced arousal can provoke increases in somatic and possibly even
      cortical arousal in normal sleepers. However, this was not accompanied by an
      enhanced ability to perform adequately on a driving simulator test.

PMID- 15560765
TI  - Inter- and intra-individual variability in performance near the circadian nadir
      during sleep deprivation.
AB  - The study purpose was to assess inter- and intra-individual variability in
      neurobehavioral function near the circadian nadir during sleep deprivation and
      conduct exploratory factor analyses to assess relationships among alertness and
      performance measures during sleep deprivation. Twenty-five healthy individuals
      (16 females) aged 18-25 years participated. Participants were sleep deprived for
      two nights under controlled laboratory conditions using a modified constant
      routine procedure. A comprehensive battery of neurobehavioral performance tests,
      subjective sleepiness (SSS), and objective alertness (MWT) were assessed.
      Seventeen of the 22 neurobehavioral measures were impaired by sleep deprivation
      (all P < 0.01). The use of multiple neurobehavioral performance measures revealed
      impairments for all individuals during sleep deprivation. However, sleep
      deprivation effects were task dependent within and between individuals. Gender
      contributed minimally to inter-individual variability in performance. Exploratory
      factor analysis reduced the 22 measures to seven independent factors. Our
      findings indicate that no individual was especially vulnerable or resistant to
      the performance impairing effects of sleep deprivation. Instead, inter- and intra
      individual variability in performance during sleep deprivation was task
      dependent. The finding that subjective sleepiness and objective alertness were
      not related to any performance measure during sleep deprivation suggests that
      these measures may assess independent brain functions.

PMID- 15560766
TI  - Incorporation of presleep stimuli into dream contents: evidence for a
      consolidation effect on declarative knowledge during REM sleep?
AB  - Presleep stimuli to be retained for further recall is often incorporated into
      dream contents. To establish whether processing for insertion into dream contents
      may improve consolidation, we compared the retention rate at delayed recall of
      contents resulting from incorporation of presleep sentence-stimuli with those of
      other contents of the same dream experiences. We hypothesized that association
      with a cognitive task of recall facilitates access to recently acquired items of
      declarative knowledge such as presleep stimuli, and triggers the deep elaboration
      of their semantic features, which involves rehearsal. Twelve subjects were given
      a task of delayed recall for three nonsense sentences delivered once a time
      before each of the sleep (re-)onsets over an experimental night. After each
      awakening in rapid eye movement sleep, subjects were asked to report dream
      experience and recall the sentence to be retained. In the morning, after
      spontaneous awakening, subjects were unexpectedly requested to again report their
      dream experiences and to recall the stimuli. Two pairs of judges independently
      identified possible incorporations of the stimuli, and parsed dream reports into
      propositional content units. The proportion of night reports with at least one
      incorporation of the stimulus delivered (i.e. valid incorporations) was higher
      than that of reports with contents similar to a stimulus(-i) not yet delivered
      (forward pseudo-incorporations) or delivered prior to an earlier sleep period
      (backward pseudo-incorporations). The proportion of content units common to night
      and morning reports (considered to be better consolidated) was significantly
      higher for incorporated contents than for other contents, including pseudo
      incorporated contents. Instead, the retention at morning recall of words of
      sentence-stimuli corresponding to incorporated contents was not significantly
      higher than that of other words. The better retention of incorporated contents
      provides a partial confirmation (that is, limited to the output of the
      processing) that a generation effect, which benefits retention of actively
      processed information, is operative during sleep as well as in waking.

PMID- 15560767
TI  - Immediate and delayed incorporations of events into dreams: further replication
      and implications for dream function.
AB  - The incorporation of memories into dreams is characterized by two types of
      temporal effects: the day-residue effect, involving immediate incorporations of
      events from the preceding day, and the dream-lag effect, involving incorporations
      delayed by about a week. This study was designed to replicate these two effects
      while controlling several prior methodological problems and to provide
      preliminary information about potential functions of delayed event
      incorporations. Introductory Psychology students were asked to recall dreams at
      home for 1 week. Subsequently, they were instructed to select a single dream and
      to retrieve past events related to it that arose from one of seven randomly
      determined days prior to the dream (days 1-7). They then rated both their
      confidence in recall of events and the extent of correspondence between events
      and dreams. Judges evaluated qualities of the reported events using scales
      derived from theories about the function of delayed incorporations. Average
      ratings of correspondences between dreams and events were high for predream days
      1 and 2, low for days 3 and 4 and high again for days 5-7, but only for
      participants who rated their confidence in recall of events as high and only for
      females. Delayed incorporations were more likely than immediate incorporations to
      refer to events characterized by interpersonal interactions, spatial locations,
      resolved problems and positive emotions. The findings are consistent with the
      possibility that processes with circaseptan (about 7 days) morphology underlie
      dream incorporation and that these processes subserve the functions of socio
      emotional adaptation and memory consolidation.

PMID- 15560768
TI  - Thermal acclimation of neonates to prolonged cool exposure as regards sleep
      stages.
AB  - The thermal responses of neonates during a cool acclimation period were studied
      with regard to sleep stages. Sleep stages, body temperatures and metabolic rate
      (VO2) were studied for seven neonates nursed in incubators and exposed to a cool
      temperature (thermoneutrality minus 2 degrees C) for 75 h. Each recording session
      lasted 3 h in the morning: firstly under thermoneutral baseline conditions, then
      during the first and last 3-h periods of the cool acclimation and finally during
      the last 3 h of a 24-h recovery period. Sleep structure was modified during the
      initial hours of cool exposure: the percentage of active sleep increased (AS:
      +13%, P = 0.028) at the expense of quiet sleep (QS: -11%, P = 0.043). This
      alteration in sleep structure persisted at the end of the acclimation period.
      Metabolic heat production only increased in the later period of cool acclimation.
      Throughout the cool exposure, VO2 increased more (P = 0.040) in QS (+33%) than in
      AS (+20%) so that by the end of the cool period, VO2 levels were similar in both
      sleep stages. During cool acclimation, the maintenance of homeothermy is related
      not only to a change in sleep organization but also to modifications in the
      thermoregulatory processes in both sleep stages. Considering the importance of
      AS/QS patterns in the neurobehavioral development of neonates, the present
      results could have clinical implications for the thermal management of neonates.

PMID- 15560769
TI  - The relationship between daytime exposure to light and night-time sleep in 6-12
      week-old infants.
AB  - This project investigated the relationship between exposure to light and 24-h
      patterns of sleep and crying in young, healthy, full-term babies living at home
      and following a normal domestic routine. Measures included an ankle worn activity
      monitor, an external light monitor and the Barr Baby Day Diary in which parents
      recorded periods of sleep, crying, feeding and other behaviours at 5-min
      intervals throughout the 24-h period. Fifty-six babies (26 males and 30 females)
      were monitored across three consecutive days at 6, 9 and 12 weeks of age. There
      was an early evening peak in crying which was associated with reduced sleep at 6
      weeks. Across the trials there was a gradual shift towards a greater proportion
      of sleep occurring at night. Sleeping well at 6 weeks was a good indication of
      more night-time sleep at 9 and 12 weeks. Babies who slept well at night were
      exposed to significantly more light in the early afternoon period. These data
      suggest that light in the normal domestic setting influences the development of
      the circadian system.

PMID- 15560770
TI  - Testing thermogenesis as the basis for the evolution of cetacean sleep
      phenomenology.
AB  - Cetacean sleep phenomenology consists of a combination of unihemispheric slow
      wave sleep and a massive reduction in the amount of rapid eye movement sleep.
      Despite various proposals, the selection pressure driving the evolution of this
      combined sleep phenomenology is unknown. It was recently suggested that the need
      to produce heat in the thermally challenging aquatic environment might have been
      the selection pressure. Mechanisms of heat loss and heat production can be
      measured directly or indirectly. The present study was designed to test the
      thermogenetic proposal by recording indirect measurements of heat loss (surface
      area to volume ratio) and heat production (tail-beats per minute). A strong
      correlation was found between these two parameters, such that increases in
      potential heat loss were matched by increases in potential heat production. This
      result suggests that the need to compensate for heat loss can provide an
      evolutionary rationale for the appearance of extant cetacean sleep physiology.

PMID- 15560771
TI  - Sleep quantity, sleep difficulties and their perceived consequences in a
      representative sample of some 2000 British adults.
AB  - Sleep problems and sleep restriction are popular topics of discussion, but few
      representative data are available. We document Britain's sleep based on a
      nationally representative sample of 1997, 16-93 year olds, who participated in
      face-to-face interviews. Fifty-eight per cent of respondents reported sleep
      problems on one or more nights the previous week and 18% reported that the sleep
      they obtained was insufficient on the majority of nights. Sleep durations were
      longest in the youngest participants (16-24 years), who slept on average 1 h
      longer than the 7.04 (SD 1.55) sample average. Sleep duration showed no
      appreciable change beyond middle age. Men and women reported sleeping similar
      amounts but women reported more sleep problems. Men reported sleeping less when
      there were more children in their household. Workers (i.e. employees) reported
      sleeping less on workdays than on non-workdays, but those based at home and those
      not employed did not. Inability to switch off from work was related to sleep
      duration on non-workdays. Across all participants average sleep duration
      exhibited a non-monotonic association with quality of life (i.e. contribution of
      sleep to energy, satisfaction and success in work, home and leisure activities).
      Quality of life was positively associated with sleep duration, for durations up
      to 9 h, but negatively associated with quality of life beyond this. Comparison of
      our data with the US national sleep poll revealed that Britain sleeps as little
      or less, whereas a comparison with data reported 40 years ago revealed no
      statistically reliable reductions. Although we may not sleep less than four
      decades ago, when we report sleeping less we also tend to associate that lack of
      sleep with poor performance and quality of life.

PMID- 15560772
TI  - Daytime variation in performance and tiredness/sleepiness ratings in patients
      with insomnia, narcolepsy, sleep apnea and normal controls.
AB  - Daytime tiredness or sleepiness and deficits in cognitive performance are common
      complaints in sleep disordered patients. Till now there are few studies comparing
      patients from different diagnostic groups of sleep disorders in the same
      experimental protocol. We studied the time course of cognitive functions and
      subjective alertness in a parallel group design with four groups of patients
      [narcolepsy, untreated or treated obstructive sleep apnea (OSA), or
      psychophysiological insomnia] and a control group of subjects without sleep
      complaints. Each group consisted of 10 subjects, matched for age and gender.
      After a night with polysomnography, subjects were studied for 10 h from 08:00
      hours to 18:00 hours at 20 min intervals under standardized environmental
      conditions. Four psychological tests were applied, (1) a critical flicker fusion
      (CFF) test to measure optical fusion threshold (alertness); (2) a paper-and
      pencil visual line tracking test (selective attention); (3) a visual analog scale
      (VAS) for tiredness/sleepiness; and (4) the Tiredness Symptoms Scale (TSS), a 14
      items check list. Each test session lasted for 8 min, followed by a 12 min pause.
      The level and time course of cognitive performance and self-rating data were
      analysed with hierarchical linear mixed effects models. Cognitive tests showed
      decrements in alertness and selective attention in untreated patients with
      insomnia, narcolepsy, and sleep apnea. Narcoleptic patients and untreated OSA had
      a lower CFF threshold than controls, and for narcoleptic patients the time course
      differed from that of all other groups. In the visual tracking test the
      performance of all groups of patients was worse compared with normal controls.
      Self-rated tiredness/sleepiness was significantly more pronounced in the three
      groups of untreated patients than in control subjects.

PMID- 15560773
TI  - Effect of cognitive behavioural therapy for insomnia on sleep architecture and
      sleep EEG power spectra in psychophysiological insomnia.
AB  - There is now an overwhelming preponderance of evidence that cognitive behavioural
      therapy for insomnia (CBT-I) is effective, as effective as sedative hypnotics
      during acute treatment (4-8 weeks), and is more effective in long term (following
      treatment). Although the efficacy of CBT-I in the treatment of chronic insomnia
      is well known, however there is little objective data on the effects of CBT-I on
      sleep architecture and sleep EEG power densities. The present study evaluated,
      first, subjective change in sleep quality and quantity, and secondly the
      modifications occurring in polysomnography and EEG power densities during sleep
      after 8 weeks of CBT-I. Nine free drug patients with psychophysiological
      insomnia, aged 33-62 years (mean age 47 +/- 9.7 years), seven female and two male
      participated in the study. Self-report questionnaires were administered 1 week
      before and 1 week after CBT-I, a sleep diary was completed each day 1 week before
      CBT-I, during CBT-I and 1 week after CBT-I. Subjects underwent two consecutive
      polysomnographic nights before and after CBT-I. Spectral analysis was performed
      the second night following 16 h of controlled wakefulness. After CBT-I, only
      scales assessing insomnia were significantly decreased, stages 2, REM sleep and
      SWS durations were significantly increased. Slow wave activity (SWA) was
      increased and the SWA decay shortened, beta and sigma activity were reduced. In
      conclusion CBT-I improves both subjective and objective sleep quality of sleep.
      CBT-I may enhance sleep pressure and improve homeostatic sleep regulation.

PMID- 15560774
TI  - The clinical spectrum of narcolepsy with cataplexy: a reappraisal.
AB  - In the absence of a golden standard for the diagnosis of narcolepsy, the clinical
      spectrum of disorder remains controversial. The aims of this study were (1) to
      determine frequency and characteristics of sleep-wake symptoms in patients with
      narcolepsy with cataplexy, (2) to compare clinical characteristics with results
      of ancillary tests, and (3) to identify factors that discriminate narcolepsy from
      other conditions with excessive daytime sleepiness (EDS). We prospectively
      studied 57 narcoleptics with cataplexy, 56 patients with non-narcoleptic
      hypersomnia (H), and 40 normal controls (No). Based on suggested and published
      criteria, we differentiated between narcoleptics with definite cataplexy (N) and
      narcoleptics without definite cataplexy (possible cataplexy, NpC). Assessment
      consisted of questionnaires [all patients and controls, including the Ullanlinna
      Narcolepsy Score (UNS)], polysomnography (all patients), multiple sleep latency
      test (MSLT) and human leukocyte antigen typing (in most narcoleptics). A new
      narcolepsy score based on five questions was developed. Data were compared with
      those of 12 hypocretin-deficient narcoleptics (N-hd). There were significant
      differences between N and NpC (including mean sleep latency on MSLT), but none
      between N and N-hd. A score of sleep propensity during active situations (SPAS)
      and the frequency of sleep paralysis/hallucinations at sleep onset, dreams of
      flying, and history of sleep shouting discriminated N from H and No (P < 0.001).
      Cataplexy-like symptoms in H (18%) and No (8%) could be discriminated from 'true'
      cataplexy in N on the basis of topography of motor effects, triggering emotions
      and triggering situations (P < 0.001). Our narcolepsy score had a similar
      sensitivity (96% versus 98%) but a higher specificity (98% versus 56%) than the
      UNS. Analysis of co-occurring symptoms in narcolepsy revealed two symptom
      complexes: EDS, cataplexy, automatic behaviors; and sleep paralysis,
      hallucinations, parasomnias. Low/undetectable cerebrospinal fluid hypocretin-1
      levels and a history of definite cataplexy identify similar subgroups of
      narcoleptics. Specific questions on severity of EDS (SPAS score) and
      characteristics of cataplexy allow the recognition of subgroups of narcoleptics
      and their differentiation from non-narcoleptic EDS patients, including those
      reporting cataplexy-like episodes. The existence of co-occurring symptoms
      supports the hypothesis of a distinct pathophysiology of single narcoleptic
      symptoms.

PMID- 15560775
TI  - Comparison of the maintenance of wakefulness test (MWT) to a modified behavioral
      test (OSLER) in the evaluation of daytime sleepiness.
AB  - The objectives were to evaluate the correlation between sleep onset as defined by
      the Oxford sleep resistance (OSLER) test and by simultaneous
      electroencephalography (EEG) and to determine the correlation between sleep
      latencies measured by the OSLER test and maintenance of wakefulness test (MWT)
      performed on the same day. This was a prospective, cross-sectional study carried
      out in a tertiary-care university-based sleep laboratory. Participants were 11
      consecutive subjects presenting to the sleep center with clinical indications for
      nocturnal polysomnography and MWT. The interventions included MWT and OSLER test.
      Mean sleep latencies for the OSLER and MWT in each subject were closely
      correlated (ICC = 0.94, [Intra-class correlation]P < 0.05). Sleep latency by
      OSLER and simultaneous measurement of EEG also had excellent agreement (ICC =
      0.91) with a bias of -0.97 min. The OSLER test is a practical and reliable tool
      for evaluating daytime sleepiness when compared with the MWT. No obvious
      systematic adaptation was seen during sequential OSLER test performance. Given
      its portability and minimal technical requirements, the OSLER test may be useful
      for large-scale applications in the evaluation of daytime wakefulness and
      vigilance.

PMID- 15560776
TI  - Models and mechanisms of O-O bond activation by cytochrome P450. A critical
      assessment of the potential role of multiple active intermediates in oxidative
      catalysis.
AB  - Cytochrome P450 enzymes promote a number of oxidative biotransformations
      including the hydroxylation of unactivated hydrocarbons. Whereas the long
      standing consensus view of the P450 mechanism implicates a high-valent iron-oxene
      species as the predominant oxidant in the radicalar hydrogen abstraction/oxygen
      rebound pathway, more recent studies on isotope partitioning, product
      rearrangements with 'radical clocks', and the impact of threonine mutagenesis in
      P450s on hydroxylation rates support the notion of the nucleophilic and/or
      electrophilic (hydro)peroxo-iron intermediate(s) to be operative in P450
      catalysis in addition to the electrophilic oxenoid-iron entity; this may
      contribute to the remarkable versatility of P450s in substrate modification.
      Precedent to this mechanistic concept is given by studies with natural and
      synthetic P450 biomimics. While the concept of an alternative electrophilic
      oxidant necessitates C-H hydroxylation to be brought about by a cationic
      insertion process, recent calculations employing density functional theory favour
      a 'two-state reactivity' scenario, implicating the usual ferryl-dependent oxygen
      rebound pathway to proceed via two spin states (doublet and quartet); state
      crossing is thought to be associated with either an insertion or a radicalar
      mechanism. Hence, challenge to future strategies should be to fold the disparate
      and sometimes contradictory data into a harmonized overall picture.

PMID- 15560777
TI  - The Thermoplasma acidophilum Lon protease has a Ser-Lys dyad active site.
AB  - A gene with significant similarity to bacterial Lon proteases was identified
      during the sequencing of the genome of the thermoacidophilic archaeon
      Thermoplasma acidophilum. Protein sequence comparison revealed that Thermoplasma
      Lon protease (TaLon) is more similar to the LonB proteases restricted to Gram
      positive bacteria than to the widely distributed bacterial LonA. However, the
      active site residues of the protease and ATPase domain are highly conserved in
      all Lon proteases. Using site-directed mutagenesis we show here that TaLon and
      EcLon, and probably all other Lon proteases, contain a Ser-Lys dyad active site.
      The TaLon active site mutants were fully assembled and, similar to TaLon wild
      type, displayed an apparent molar mass of 430 kDa upon gelfiltration. This would
      be consistent with a hexameric complex and indeed electron micrographs of TaLon
      revealed ring-shaped particles, although of unknown symmetry. Comparison of the
      ATPase activity of Lon wild-type from Thermoplasma or Escherichia coli with
      respective protease active site mutants revealed differences in Km and V values.
      This suggests that in the course of protein degradation by wild-type Lon the
      protease domain might influence the activity of the ATPase domain.

PMID- 15560778
TI  - Internalization of the human CRF receptor 1 is independent of classical
      phosphorylation sites and of beta-arrestin 1 recruitment.
AB  - The corticotropin releasing factor receptor 1 (CRFR1) belongs to the superfamily
      of G-protein coupled receptors. Though CRF is involved in the aetiology of
      several stress-related disorders, including depression and anxiety, details of
      CRFR1 regulation such as internalization remain uncharacterized. In the present
      study, agonist-induced internalization of CRFR1 in HEK293 cells was visualized by
      confocal microscopy and quantified using the radioligand 125I-labelled sauvagine.
      Recruitment of beta-arrestin 1 in response to receptor activation was
      demonstrated by confocal microscopy. The extent of 125I-labelled sauvagine
      stimulated internalization was significantly impaired by sucrose, indicating the
      involvement of clathrin-coated pits. No effect on the extent of internalization
      was observed in the presence of the second messenger dependent kinase inhibitors
      H-89 and staurosporine, indicating that cAMP-dependent protein kinase and protein
      kinase C are not prerequisites for CRFR1 internalization. Surprisingly, deletion
      of all putative phosphorylation sites in the C-terminal tail, as well as a
      cluster of putative phosphorylation sites in the third intracellular loop, did
      not affect receptor internalization. However, these mutations almost abolished
      the recruitment of beta-arrestin 1 following receptor activation. In conclusion,
      we demonstrate that CRFR1 internalization is independent of phosphorylation sites
      in the C-terminal tail and third intracellular loop, and the degree of beta
      arrestin 1 recruitment.

PMID- 15560779
TI  - An extension to the metabolic control theory taking into account correlations
      between enzyme concentrations.
AB  - The classical metabolic control theory [Kacser, H. & Burns, J.A. (1973) Symp.
      Soc. Exp. Biol.27, 65-104; Heinrich, R. & Rapoport, T. (1974) Eur. J. Biochem.42,
      89-95.] does not take into account experimental evidence for correlations between
      enzyme concentrations in the cell. We investigated the implications of two causes
      of linear correlations: competition between enzymes, which is a mere physical
      adaptation of the cell to the limitation of resources and space, and regulatory
      correlations, which result from the existence of regulatory networks. These
      correlations generate redistribution of enzyme concentrations when the
      concentration of an enzyme varies; this may dramatically alter the flux and
      metabolite concentration curves. In particular, negative correlations cause the
      flux to have a maximum value for a defined distribution of enzyme concentrations.
      Redistribution coefficients of enzyme concentrations allowed us to calculate the
      'combined response coefficient' that quantifies the response of flux or
      metabolite concentration to a perturbation of enzyme concentration.

PMID- 15560780
TI  - Natural-abundance isotope ratio mass spectrometry as a means of evaluating carbon
      redistribution during glucose-citrate cofermentation by Lactococcus lactis.
AB  - The cometabolism of citrate and glucose by growing Lactococcus lactis ssp. lactis
      bv. diacetylactis was studied using a natural-abundance stable isotope technique.
      By a judicious choice of substrates differing slightly in their 13C/12C ratios,
      the simultaneous metabolism of citrate and glucose to a range of compounds was
      analysed. These end-products include lactate, acetate, formate, diacetyl and
      acetoin. All these products have pyruvate as a common intermediate. With the
      objective of estimating the degree to which glucose and citrate metabolism
      through pyruvate may be differentially regulated, the delta13C values of the
      products accumulated over a wide range of concentrations of citrate and glucose
      were compared. It was found that, whereas the relative accumulation of different
      products responds to both the substrate concentration and the ratio between the
      substrates, the delta13C values of the products primarily reflect the
      availability of the two substrates over the entire range examined. It can be
      concluded that in actively growing L. lactis the maintenance of pyruvate
      homeostasis takes precedence over the redox status of the cells as a regulatory
      factor.

PMID- 15560781
TI  - Regulation of phospholipid biosynthesis by phosphatidylinositol transfer protein
      Sec14p and its homologues. A critical role for phosphatidic acid.
AB  - Transcription of yeast phospholipid biosynthesis structural genes, which contain
      an inositol-sensitive upstream activating sequence in their promoters, responds
      to the availability of the soluble precursors inositol and choline and to changes
      in phospholipid metabolism. The INO1 gene is deregulated (derepressed when
      inositol is present) under the conditions of increased phosphatidylcholine
      (PtdCho) turnover, as occurs in the sec14Delta cki1Delta strain (SEC14 encodes
      the major yeast phosphatidylinositol transfer protein; CKI1 encodes choline
      kinase of the cytidine diphosphate choline pathway of PtdCho biosynthesis). Five
      proteins (Sfhp) share sequence homology with phosphatidylinositol transfer
      protein Sec14p. Two (Sfh2p and Sfh4p), when overexpressed largely complement the
      otherwise essential Sec14p requirement concerning growth and secretion. In this
      study, we analysed the ability of Sec14 homologues to correct the defect in
      regulation of phospholipid biosynthesis resulting from defective or missing
      Sec14p. We also analysed how PtdCho turnover relates to the transcriptional
      regulation of phospholipid biosynthesis. The results show that (a) none of the
      Sec14 homologues was able to substitute for Sec14p in its regulatory aspects of
      phospholipid biosynthesis, (b) removal of phospholipase D activity corrected the
      aberrant INO1 gene regulation in yeast strains with otherwise high PtdCho
      turnover, and (c) increased steady-state phosphatidic acid levels correlated with
      derepressed levels of the INO1 gene. Overall, the results support the model in
      which high phosphatidic acid levels lead to derepression of the genes of
      phospholipid biosynthesis [Henry, S.A. & Patton-Vogt, J.L. (1998) Prog. Nucleic
      Acid Res. Mol. Biol.61, 133-179].

PMID- 15560782
TI  - Functional analysis of the basic helix-loop-helix transcription factor DEC1 in
      circadian regulation. Interaction with BMAL1.
AB  - The basic helix-loop-helix transcription factor DEC1 is expressed in a circadian
      manner in the suprachiasmatic nucleus where it seems to play a role in regulating
      the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoter.
      The interaction of DEC1 with BMAL1 has been suggested as one of the molecular
      mechanisms of the suppression [Honma, S., Kawamoto, T., Takagi, Y., Fujimoto, K.,
      Sato, F., Noshiro, M., Kato, Y. & Honma, K. (2002) Nature 419, 841-844]. Deletion
      analysis of DEC1 demonstrated that its N-terminal region, which includes the
      basic helix-loop-helix domain, was essential for both the suppressive activity
      and the interaction with BMAL1, as DEC1 lacking the basic region did not show any
      suppression or interaction. Furthermore, we found that Arg65 in the basic region,
      which is conserved among group B basic helix-loop-helix proteins, was responsible
      for the suppression, for the interaction with BMAL1 and for its binding to CACGTG
      E-boxes. However, substitution of His57 for Ala significantly reduced the E-box
      binding activity of DEC1, although it did not affect the interaction with BMAL1
      or suppression of CLOCK/BMAL1-induced transcription. On the other hand, the basic
      region-deleted DEC1 acted in a dominant-negative manner for DEC1 activity,
      indicating that the basic region was not required for homodimer formation of
      DEC1. Moreover, mutant DEC1 also counteracted DEC2-mediated suppressive activity
      in a dominant-negative manner. The heterodimer formation of DEC1 and DEC2 was
      confirmed by pull-down assay. These findings suggest that the basic region of
      DEC1 participates in the transcriptional regulation through a protein-protein
      interaction with BMAL1 and DNA binding to the E-box.

PMID- 15560783
TI  - Insights into the reaction mechanism of glycosyl hydrolase family 49. Site
      directed mutagenesis and substrate preference of isopullulanase.
AB  - Aspergillus niger isopullulanase (IPU) is the only pullulan-hydrolase in glycosyl
      hydrolase (GH) family 49 and does not hydrolyse dextran at all, while all other
      GH family 49 enzymes are dextran-hydrolysing enzymes. To investigate the common
      catalytic mechanism of GH family 49 enzymes, nine mutants were prepared to
      replace residues conserved among GH family 49 (four Trp, three Asp and two Glu).
      Homology modelling of IPU was also carried out based on the structure of
      Penicillium minioluteum dextranase, and the result showed that Asp353, Glu356,
      Asp372, Asp373 and Trp402, whose substitutions resulted in the reduction of
      activity for both pullulan and panose, were predicted to be located in the
      negatively numbered subsites. Three Asp-mutated enzymes, D353N, D372N and D373N,
      lost their activities, indicating that these residues are candidates for the
      catalytic residues of IPU. The W402F enzyme significantly reduced IPU activity,
      and the Km value was sixfold higher and the k0 value was 500-fold lower than
      those for the wild-type enzyme, suggesting that Trp402 is a residue participating
      in subsite -1. Trp31 and Glu273, whose substitutions caused a decrease in the
      activity for pullulan but not for panose, were predicted to be located in the
      interface between N-terminal and beta-helical domains. The substrate preference
      of the negatively numbered subsites of IPU resembles that of GH family 49
      dextranases. These findings suggest that IPU and the GH family 49 dextranases
      have a similar catalytic mechanism in their negatively numbered subsites in spite
      of the difference of their substrate specificities.

PMID- 15560784
TI  - Molecular evolution of shark and other vertebrate DNases I.
AB  - We purified pancreatic deoxyribonuclease I (DNase I) from the shark Heterodontus
      japonicus using three-step column chromatography. Although its enzymatic
      properties resembled those of other vertebrate DNases I, shark DNase I was unique
      in being a basic protein. Full-length cDNAs encoding the DNases I of two shark
      species, H. japonicus and Triakis scyllia, were constructed from their total
      pancreatic RNAs using RACE. Nucleotide sequence analyses revealed two structural
      alterations unique to shark enzymes: substitution of two Cys residues at
      positions 101 and 104 (which are well conserved in all other vertebrate DNases I)
      and insertion of an additional Thr or Asn residue into an essential Ca(2+)
      binding site. Site-directed mutagenesis of shark DNase I indicated that both of
      these alterations reduced the stability of the enzyme. When the signal sequence
      region of human DNase I (which has a high alpha-helical structure content) was
      replaced with its amphibian, fish and shark counterparts (which have low alpha
      helical structure contents), the activity expressed by the chimeric mutant
      constructs in transfected mammalian cells was approximately half that of the wild
      type enzyme. In contrast, substitution of the human signal sequence region into
      the amphibian, fish and shark enzymes produced higher activity compared with the
      wild-types. The vertebrate DNase I family may have acquired high stability and
      effective expression of the enzyme protein through structural alterations in both
      the mature protein and its signal sequence regions during molecular evolution.

PMID- 15560785
TI  - Regulation of connective tissue growth factor (CTGF/CCN2) gene transcription and
      mRNA stability in smooth muscle cells. Involvement of RhoA GTPase and p38 MAP
      kinase and sensitivity to actin dynamics.
AB  - Connective tissue growth factor (CTGF/CCN2) is an immediate early gene-encoded
      polypeptide modulating cell growth and collagen synthesis. The importance of
      CTGF/CCN2 function is highlighted by its disregulation in fibrotic disorders. In
      this study, we investigated the regulation and signaling pathways that are
      required for various stimuli of intracellular signaling events to induce the
      expression of the endogenous CTGF/CCN2 gene in smooth muscle cells. Incubation
      with the bioactive lysolipid sphingosine 1-phosphate (S1P) produced a threefold
      increase, whereas stimulation with either fetal bovine serum or anisomycin
      induced an even stronger activation (eightfold) of CTGF/CCN2 expression. Using a
      combination of pathway-specific inhibitors and mutant forms of signaling
      molecules, we found that S1P- and fetal bovine serum-induced CTGF/CCN2 expression
      were dependent on both RhoA GTPase and p38 mitogen-activated protein kinase
      transduction pathways, whereas the effects of anisomycin largely involved p38 and
      phosphatidyl inositol 3-kinase signaling mechanisms. However, activation via
      these signaling events was absolutely dependent on actin cytoskeleton integrity.
      In particular, RhoA-dependent regulation of the CTGF/CCN2 gene was concomitant to
      increased polymerization of actin microfilaments resulting in decreased G- to F
      actin ratio and appeared to be achieved at the transcriptional level. The p38
      signaling pathway was RhoA-independent and led to CTGF/CCN2 mRNA stabilization.
      Use of actin-binding drugs showed that the actual physical state of monomeric G
      actin is a critical determinant for CTGF/CCN2 gene induction. These data indicate
      that distinct cytoskeletally based signaling events within the intracellular
      signaling machinery affect either transcriptionally or post-transcriptionally the
      expression of the CTGF/CCN2 gene in smooth muscle cells.

PMID- 15560786
TI  - Role of hydroxyl group and R/S configuration of isostere in binding properties of
      HIV-1 protease inhibitors.
AB  - The crystal structure of the complex between human immunodeficiency virus type 1
      (HIV-1) protease and a peptidomimetic inhibitor of ethyleneamine type has been
      refined to R factor of 0.178 with diffraction limit 2.5 A. The peptidomimetic
      inhibitor Boc-Phe-Psi[CH2CH2NH]-Phe-Glu-Phe-NH2 (denoted here as OE) contains the
      ethyleneamine replacement of the scissile peptide bond. The inhibitor lacks the
      hydroxyl group which is believed to mimic tetrahedral transition state of
      proteolytic reaction and thus is suspected to be necessary for good properties of
      peptidomimetic HIV-1 protease inhibitors. Despite the missing hydroxyl group the
      inhibition constant of OE is 1.53 nm and it remains in the nanomolar range also
      towards several available mutants of HIV-1 protease. The inhibitor was found in
      the active site of protease in an extended conformation with a unique hydrogen
      bond pattern different from hydroxyethylene and hydroxyethylamine inhibitors. The
      isostere nitrogen forms a hydrogen bond to one catalytic aspartate only. The
      other aspartate forms two weak hydrogen bridges to the ethylene group of the
      isostere. A comparison with other inhibitors of this series containing isostere
      hydroxyl group in R or S configuration shows different ways of accommodation of
      inhibitor in the active site. Special attention is devoted to intermolecular
      contacts between neighbouring dimers responsible for mutual protein adhesion and
      for a special conformation of Met46 and Phe53 side chains not expected for free
      protein in water solution.

PMID- 15560787
TI  - Modulation of cyclin D1 and early growth response factor-1 gene expression in
      interleukin-1beta-treated rat smooth muscle cells by n-6 and n-3 polyunsaturated
      fatty acids.
AB  - The proliferation of smooth muscle cells (SMC) is a key event in the development
      of atherosclerosis. In addition to growth factors or cytokines, we have shown
      previously that n-3 polyunsaturated fatty acids (PUFAs) act in opposition to n-6
      PUFAs by modulating various steps of the inflammatory process. We have
      investigated the molecular mechanisms by which the incorporation of the n-6 PUFA,
      arachidonic acid, increases the proliferation of rat SMC treated with interleukin
      1beta, while the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA), elicit no mitogenic response. Incorporation of EPA or DHA into SMC, which
      are then activated by interleukin-1beta to mimic inflammation, decreases promoter
      activity of the cyclin D1 gene and phosphorylation of the retinoblastoma protein.
      Together, our data demonstrate that n-3 effects are dependent on the Ras/Raf
      1/extracellular signal regulated kinase (ERK)/mitogen-activated protein kinase
      pathway, and that down-regulation of the cyclin D1 promoter activity is mediated
      by the specific binding of the early growth response factor-1. Finally, we have
      shown that the incorporation of EPA and DHA also increased the concentration of
      caveolin-1 and caveolin-3 in caveolae, which correlated with n-3 PUFA inhibition
      of SMC proliferation through the mitogen-activated protein kinase pathway. We
      provide evidence indicating that, in contrast to n-6 PUFAs, n-3 PUFAs exert
      antiproliferative effects on SMC through the mitogen-activated protein kinase/ERK
      pathway.

PMID- 15560788
TI  - Context-dependent effects of proline residues on the stability and folding
      pathway of ubiquitin.
AB  - Substitution of trans-proline at three positions in ubiquitin (residues 19, 37
      and 38) produces significant context-dependent effects on protein stability (both
      stabilizing and destabilizing) that reflect changes to a combination of
      parameters including backbone flexibility, hydrophobic interactions, solvent
      accessibility to polar groups and intrinsic backbone conformational preferences.
      Kinetic analysis of the wild-type yeast protein reveals a predominant fast
      folding phase which conforms to an apparent two-state folding model. Temperature
      dependent studies of the refolding rate reveal thermodynamic details of the
      nature of the transition state for folding consistent with hydrophobic collapse
      providing the overall driving force. Bronsted analysis of the refolding and
      unfolding rates of a family of mutants with a variety of side chain substitutions
      for P37 and P38 reveals that the two prolines, which are located in a surface
      loop adjacent to the C terminus of the main alpha-helix (residues 24-33), are not
      significantly structured in the transition state for folding and appear to be
      consolidated into the native structure only late in the folding process. We draw
      a similar conclusion regarding position 19 in the loop connecting the N-terminal
      beta-hairpin to the main alpha-helix. The proline residues of ubiquitin are
      passive spectators in the folding process, but influence protein stability in a
      variety of ways.

PMID- 15560789
TI  - Alternative initiation of transcription of the human presenilin 1 gene in SH-SY5Y
      and SK-N-SH cells. The role of Ets factors in the regulation of presenilin 1.
AB  - We have identified DNA sequences required for the expression of the presenilin 1
      (PS1) gene. A promoter region has been mapped in SK-N-SH cells and includes
      sequences between -118 and +178 flanking the major initiation site (+1). The PS1
      gene is also efficiently transcribed in the SH-SY5Y subclone of SK-N-SH cells.
      However the promoter appears to be utilized in alternative ways in both cell
      types. Sequences both upstream as well as downstream from the initiation site
      mapped in SK-N-SH cells were shown by 5'- and 3'-deletion analysis to play a
      crucial role in both cell lines. However, in SH-SY5Y cells either upstream or
      downstream sequences are sufficient to direct transcription, whereas in SK-N-SH
      cells 5'-deletions past the +1 site eliminate over 95% of transcription. Several
      Ets motifs (GGAA) as well as Sp1 motifs [(G/T)GGCGGRRY] are juxtaposed both
      upstream and downstream from +1. To understand how the promoter may be utilized
      alternatively in different cell types we have examined the effect of point
      mutations in these elements. Altering an Ets motif at -10 eliminates 80% of
      transcription in SK-N-SH cells whereas the same mutation has only a minor effect
      in SH-SY5Y cells. Conversely, mutation of the Ets element at +90, which
      eliminates 70% of transcription in SH-SY5Y cells, has a lesser effect in SK-N-SH
      cells. In both cell types a promoter including mutations at both -10 and +90
      sites loses over 90% transcription activity indicating the crucial importance of
      these two Ets motifs. The effect of Sp1 mutations appears to be similar in both
      cell types. Hence the differential expression in each cell type may be at least
      partially determined by Ets factors and the -10/+90 sites. We have identified
      several Ets factors that recognize specifically the -10 Ets motif by the yeast
      one-hybrid selection including avian erythroblastosis virus E26 oncogene
      homologue 2, Ets-like gene 1, Ets translocation variant 1 and Ets related
      molecule (ERM). We show here that ERM specifically recognizes Ets motifs on the
      PS1 promoter located at -10 as well as downstream at +90, +129 and +165 and
      activates PS1 transcription with promoter fragments containing or not the -10 Ets
      site.

PMID- 15560790
TI  - Three-dimensional structure of a thermostable native cellobiohydrolase, CBH IB,
      and molecular characterization of the cel7 gene from the filamentous fungus,
      Talaromyces emersonii.
AB  - The X-ray structure of native cellobiohydrolase IB (CBH IB) from the filamentous
      fungus Talaromyces emersonii, PDB 1Q9H, was solved to 2.4 A by molecular
      replacement. 1Q9H is a glycoprotein that consists of a large, single domain with
      dimensions of approximately 60 A x 40 A x 50 A and an overall beta-sandwich
      structure, the characteristic fold of Family 7 glycosyl hydrolases (GH7). It is
      the first structure of a native glycoprotein and cellulase from this thermophilic
      eukaryote. The long cellulose-binding tunnel seen in GH7 Cel7A from Trichoderma
      reesei is conserved in 1Q9H, as are the catalytic residues. As a result of
      deletions and other changes in loop regions, the binding and catalytic properties
      of T. emersonii 1Q9H are different. The gene (cel7) encoding CBH IB was isolated
      from T. emersonii and expressed heterologously with an N-terminal polyHis-tag, in
      Escherichia coli. The deduced amino acid sequence of cel7 is homologous to fungal
      cellobiohydrolases in GH7. The recombinant cellobiohydrolase was virtually
      inactive against methylumberiferyl-cellobioside and chloronitrophenyl-lactoside,
      but partial activity could be restored after refolding of the urea-denatured
      enzyme. Profiles of cel7 expression in T. emersonii, investigated by Northern
      blot analysis, revealed that expression is regulated at the transcriptional
      level. Putative regulatory element consensus sequences for cellulase
      transcription factors have been identified in the upstream region of the cel7
      genomic sequence.

PMID- 15560791
TI  - Structural studies of the capsular polysaccharide and lipopolysaccharide O
      antigen of Aeromonas salmonicida strain 80204-1 produced under in vitro and in
      vivo growth conditions.
AB  - Aeromonas salmonicida is a pathogenic aquatic bacterium and the causal agent of
      furunculosis in salmon. In the course of this study, it was found that when grown
      in vitro on tryptic soy agar, A. salmonicida strain 80204-1 produced a capsular
      polysaccharide with the identical structure to that of the lipopolysaccharide O
      chain polysaccharide. A combination of 1D and 2D NMR methods, including a series
      of 1D analogues of 3D experiments, together with capillary electrophoresis
      electrospray MS (CE-ES-MS), compositional and methylation analyses and specific
      modifications was used to determine the structure of these polysaccharides. Both
      polymers were shown to be composed of linear trisaccharide repeating units
      consisting of 2-acetamido-2-deoxy-D-galacturonic acid (GalNAcA), 3-[(N-acetyl-L
      alanyl)amido]-3,6-dideoxy-D-glucose[3-[(N-acetyl-L-alanyl)amido]-3-deoxy-D
      quinovose, Qui3NAlaNAc] and 2-acetamido-2,6-dideoxy-D-glucose (2-acetamido-2
      deoxy-D-quinovose, QuiNAc) and having the following structure: [-->3)-alpha-D
      GalpNAcA-(1-->3)-beta-D-QuipNAc-(1-->4)-beta-D-Quip3NAlaNAc-(1-]n, where GalNAcA
      is partly presented as an amide and AlaNAc represents N-acetyl-L-alanyl group. CE
      ES-MS analysis of CPS and O-chain polysaccharide confirmed that 40% of GalNAcA
      was present in the amide form. Direct CE-ES-MS/MS analysis of in vivo cultured
      cells confirmed the formation of a novel polysaccharide, a structure also formed
      in vitro, which was previously undetectable in bacterial cells grown within
      implants in fish, and in which GalNAcA was fully amidated.

PMID- 15560792
TI  - Crystal structure of heme oxygenase-1 from cyanobacterium Synechocystis sp. PCC
      6803 in complex with heme.
AB  - Heme oxygenase (HO) catalyzes the oxidative degradation of heme utilizing
      molecular oxygen and reducing equivalents. In photosynthetic organisms, HO
      functions in the biosynthesis of such open-chain tetrapyrroles as phyto
      chromobilin and phycobilins, which are involved in the signal transduction for
      light responses and light harvesting for photosynthesis, respectively. We have
      determined the first crystal structure of a HO-1 from a photosynthetic organism,
      Synechocystis sp. PCC 6803 (Syn HO-1), in complex with heme at 2.5 A resolution.
      Heme-Syn HO-1 shares a common folding with other heme-HOs. Although the heme
      pocket of heme-Syn HO-1 is, for the most part, similar to that of mammalian HO-1,
      they differ in such features as the flexibility of the distal helix and
      hydrophobicity. In addition, 2-propanol derived from the crystallization solution
      occupied the hydrophobic cavity, which is proposed to be a CO trapping site in
      rat HO-1 that suppresses product inhibition. Although Syn HO-1 and mammalian HO-1
      are similar in overall structure and amino acid sequence (57% similarity vs.
      human HO-1), their molecular surfaces differ in charge distribution. The surfaces
      of the heme binding sides are both positively charged, but this patch of Syn HO-1
      is narrow compared to that of mammalian HO-1. This feature is suited to the
      selective binding of ferredoxin, the physiological redox partner of Syn HO-1; the
      molecular size of ferredoxin is approximately 10 kDa whereas the size of NADPH
      cytochrome P450 reductase, a reducing partner of mammalian HO-1, is approximately
      77 kDa. A docking model of heme-Syn HO-1 and ferredoxin suggests indirect
      electron transfer from an iron-sulfur cluster in ferredoxin to the heme iron of
      heme-Syn HO-1.

PMID- 15560793
TI  - Surface exposed amino acid differences between mesophilic and thermophilic
      phosphoribosyl diphosphate synthase.
AB  - The amino acid sequence of 5-phospho-alpha-D-ribosyl 1-diphosphate synthase from
      the thermophile Bacillus caldolyticus is 81% identical to the amino acid sequence
      of 5-phospho-alpha-D-ribosyl 1-diphosphate synthase from the mesophile Bacillus
      subtilis. Nevertheless the enzyme from the two organisms possesses very different
      thermal properties. The B. caldolyticus enzyme has optimal activity at 60-65
      degrees C and a half-life of 26 min at 65 degrees C, compared to values of 46
      degrees C and 60 s at 65 degrees C, respectively, for the B. subtilis enzyme.
      Chemical cross-linking shows that both enzymes are hexamers. Vmax is determined
      as 440 micromol.min(-1).mg protein(-1) and Km values for ATP and ribose 5
      phosphate are determined as 310 and 530 microM, respectively, for the B.
      caldolyticus enzyme. The enzyme requires 50 mM Pi as well as free Mg2+ for
      maximal activity. Manganese ion substitutes for Mg2+, but only at 30% of the
      activity obtained with Mg2+. ADP and GDP inhibit the B. caldolyticus enzyme in a
      cooperative fashion with Hill coefficients of 2.9 for ADP and 2.6 for GDP. Ki
      values are determined as 113 and 490 microm for ADP and GDP, respectively. At low
      concentrations ADP inhibition is linearly competitive with respect to ATP. A
      predicted structure of the B. caldolyticus enzyme based on homology modelling
      with the structure of B. subtilis 5-phospho-alpha-D-ribosyl 1-diphosphate
      synthase shows 92% of the amino acid differences to be on solvent exposed
      surfaces in the hexameric structure.

PMID- 15560794
TI  - Functional dissection of a small anaerobically induced bZIP transcription factor
      from tomato.
AB  - A small anaerobically induced tomato transcription factor was isolated from a
      subtractive library. This factor, designated ABZ1 (anaerobic basic leucine
      zipper), is anaerobically induced in fruits, leaves and roots and encodes a
      nuclear localized protein. ABZ1 shares close structural and sequence homology
      with the S-family of small basic leucine zipper (bZIP) transcription factors that
      are implicated in stress response. Nuclear localization of ABZ1 is mediated by
      the basic region and occurs under normoxic conditions. ABZ1 binds to G-box-like
      target sites as a dimer. Binding can be abolished by heterodimerization with a
      truncated protein retaining the leucine zipper but lacking the DNA binding
      domain. The protein binds in a sequence specific manner to the CaMV 35S promoter
      which is down regulated when ABZ1 is coexpressed. This correlates with the
      anaerobic down regulation of the 35S promoter in tomato and tobacco. These
      results may suggest that small bZIP proteins are involved in the negative
      regulation of gene expression under anaerobic conditions.

PMID- 15560795
TI  - Structural determination of the polar glycoglycerolipids from thermophilic
      bacteria Meiothermus taiwanensis.
AB  - The polar glycolipids were isolated from the thermophilic bacteria Meiothermus
      taiwanensis ATCC BAA-400 by ethanol extraction and purified by Sephadex LH-20 and
      silica gel column chromatography. The fatty acid composition of O-acyl groups in
      the glycolipids was obtained by gas chromatography mass spectroscopy analysis on
      their methyl esters derived from methanolysis and was made mainly of C(15:0)
      (34.0%) and C(17:0) (42.3%) fatty acids, with the majority as branched fatty
      acids (over 80%). Removal of O-acyl groups under mild basic conditions provided
      two glycolipids, which differ only in N-acyl substitution on a hexosamine.
      Electrospray mass spectroscopy analysis revealed that one has a C(17:0) N-acyl
      group and the other hydroxy C(17:0) in a ratio of about 1 : 3.5. Furthermore,
      complete de-lipidation with strong base followed by selective N-acetylation
      resulted in a homogeneous tetraglycosyl glycerol. The linkages and configurations
      of the carbohydrate moiety were then elucidated by MS and various NMR analyses.
      Thus, the major glycolipid from M. taiwanensis ATCC BAA-400 was determined with
      the following structure: alpha-Galp(1-6)-beta-Galp(1-6)-beta-GalNAcyl(1,2)-alpha
      Glc(1,1)-Gro diester, where N-acyl is C(17:0) or hydroxy C(17:0) fatty acid and
      the glycerol esters were mainly iso- and anteisobranched C(15:0) and C(17:0).

PMID- 15560796
TI  - Suppression of heat- and polyglutamine-induced cytotoxicity by nonsteroidal anti
      inflammatory drugs.
AB  - We have shown that sodium salicylate activates the heat shock promoter and
      induces the expression of heat shock proteins (hsps), with a concomitant increase
      in the thermotolerance of cells. To determine whether these effects are generally
      displayed by nonsteroidal anti-inflammatory drugs (NSAIDs), we examined the
      effects of a cyclooxygenase inhibitor, indomethacin, and a lipoxygenase
      inhibitor, nordihydroguaiaretic acid. Both inhibitors up-regulated the hsp
      promoter at 37 degrees C through the activation of heat shock factors, and
      increased cellular levels of hsps in mammalian cells, although the degree of the
      expression of hsps and thermotolerance of cells differed depending on the drugs.
      Furthermore, NSAIDs such as sodium salicylate and indomethacin suppressed the
      protein aggregation and apoptosis caused by an expanded polyglutamine tract in a
      cellular model of polyglutamine disease. These findings suggest that NSAIDs
      generally induce the expression of hsps in mammalian cells and may be used for
      the protection of cells against deleterious stressors and neurodegenerative
      diseases.

PMID- 15560797
TI  - Age-related impairment of mitochondrial matrix aconitase and ATP-stimulated
      protease in rat liver and heart.
AB  - Mitochondrial matrix proteins are sensitive to oxidative inactivation, and
      oxidized proteins are known to accumulate during ageing. The Lon protease is
      believed to play an important role in the degradation of oxidized matrix proteins
      such as oxidized aconitase. We reported previously that an age-related
      accumulation of altered proteins occurs in the liver matrix of rats and that the
      ATP-stimulated proteolytic activity, referred as to Lon-like protease activity,
      decreases considerably in 27 month-old rats, whereas no concomitant changes in
      the levels of Lon protein expression occur in the liver. Here, we report that
      this decline is associated with a decrease in the activity of aconitase, an
      essential Krebs' cycle enzyme. Contrary to what we observed in the liver, the ATP
      stimulated protease activity was found to remain constant in the heart
      mitochondrial matrix during ageing, and the levels of expression of the Lon
      protease increased in the older animals in comparison with the younger ones.
      Although the ATP-stimulated protease activity remained practically the same in
      older animals as in younger ones, a decrease in the level of aconitase activity
      was still observed. Altogether, these results indicate that matrix proteins, such
      as the critical enzymes aconitase and Lon protease, are inactivated with ageing
      and that the effects of ageing vary from one organ to another.

PMID- 15560798
TI  - The mechanism of alpha-proton isotope exchange in amino acids catalysed by
      tyrosine phenol-lyase. What is the role of quinonoid intermediates?
AB  - To shed light on the mechanism of isotopic exchange of alpha-protons in amino
      acids catalyzed by pyridoxal phosphate (PLP)-dependent enzymes, we studied the
      kinetics of quinonoid intermediate formation for the reactions of tyrosine phenol
      lyase with L-phenylalanine, L-methionine, and their alpha-deuterated analogues in
      D2O, and we compared the results with the rates of the isotopic exchange under
      the same conditions. We have found that, in the L-phenylalanine reaction, the
      internal return of the alpha-proton is operative, and allowing for its effect,
      the exchange rate is accounted for satisfactorily. Surprisingly, for the reaction
      with L-methionine, the enzymatic isotope exchange went much faster than might be
      predicted from the kinetic data for quinonoid intermediate formation. This result
      allows us to suggest the existence of an alternative, possibly concerted,
      mechanism of alpha-proton exchange.

PMID- 15560799
TI  - Regulation of the actin-myosin interaction by titin.
AB  - Titin is known to interact with actin thin filaments within the I-band region of
      striated muscle sarcomeres. In this study, we have used a titin fragment of 800
      kDa (T800) purified from striated skeletal muscle to measure the effect of this
      interaction on the functional properties of the actin-myosin complex. MALDI-TOF
      MS revealed that T800 contains the entire titin PEVK (Pro, Glu, Val, Lys-rich)
      domain. In the presence of tropomyosin-troponin, T800 increased the sliding
      velocity (both average and maximum values) of actin filaments on heavy-meromyosin
      (HMM)-coated surfaces and dramatically decreased the number of stationary
      filaments. These results were correlated with a 30% reduction in actin-activated
      HMM ATPase activity and with an inhibition of HMM binding to actin N-terminal
      residues as shown by chemical cross-linking. At the same time, T800 did not
      affect the efficiency of the Ca(2+)-controlled on/off switch, nor did it alter
      the overall binding energetics of HMM to actin, as revealed by cosedimentation
      experiments. These data are consistent with a competitive effect of PEVK domain
      containing T800 on the electrostatic contacts at the actin-HMM interface. They
      also suggest that titin may participate in the regulation of the active tension
      generated by the actin-myosin complex.

PMID- 15560800
TI  - Inhibition of pea ferredoxin-NADP(H) reductase by Zn-ferrocyanide.
AB  - Ferredoxin-NADP(H) reductases (FNRs) represent a prototype of enzymes involved in
      numerous metabolic pathways. We found that pea FNR ferricyanide diaphorase
      activity was inhibited by Zn2+ (Ki 1.57 microM). Dichlorophenolindophenol
      diaphorase activity was also inhibited by Zn2+ (Ki 1.80 microM), but the addition
      of ferrocyanide was required, indicating that the inhibitor is an arrangement of
      both ions. Escherichia coli FNR was also inhibited by Zn-ferrocyanide, suggesting
      that inhibition is a consequence of common structural features of these
      flavoenzymes. The inhibitor behaves in a noncompetitive manner for NADPH and for
      artificial electron acceptors. Analysis of the oxidation state of the flavin
      during catalysis in the presence of the inhibitor suggests that the electron
      transfer process between NADPH and the flavin is not significantly altered, and
      that the transfer between the flavin and the second substrate is mainly affected.
      Zn-ferrocyanide interacts with the reductase, probably increasing the
      accessibility of the prosthetic group to the solvent. Ferredoxin reduction was
      also inhibited by Zn-ferrocyanide in a noncompetitive manner, but the observed Ki
      was about nine times higher than those for the diaphorase reactions. The electron
      transfer to Anabaena flavodoxin was not affected by Zn-ferrocyanide. Binding of
      the apoflavodoxin to the reductase was sufficient to overcome the inhibition by
      Zn-ferrocyanide, suggesting that the interaction of FNRs with their proteinaceous
      electron partners may induce a conformational change in the reductase that alters
      or completely prevents the inhibitory effect.

PMID- 15560801
TI  - Symmetric fluoro-substituted diol-based HIV protease inhibitors. Ortho
      fluorinated and meta-fluorinated P1/P1'-benzyloxy side groups significantly
      improve the antiviral activity and preserve binding efficacy.
AB  - HIV-1 protease is a pivotal enzyme in the later stages of the viral life cycle
      which is responsible for the processing and maturation of the virus particle into
      an infectious virion. As such, HIV-1 protease has become an important target for
      the treatment of AIDS, and efficient drugs have been developed. However, negative
      side effects and fast emerging resistance to the current drugs have necessitated
      the development of novel chemical entities in order to exploit different
      pharmacokinetic properties as well as new interaction patterns. We have used X
      ray crystallography to decipher the structure-activity relationship of fluoro
      substitution as a strategy to improve the antiviral activity and the protease
      inhibition of C2-symmetric diol-based inhibitors. In total we present six
      protease-inhibitor complexes at 1.8-2.3 A resolution, which have been
      structurally characterized with respect to their antiviral and inhibitory
      activities, in order to evaluate the effects of different fluoro-substitutions.
      These C2-symmetric inhibitors comprise mono- and difluoro-substituted benzyloxy
      side groups in P1/P1' and indanoleamine side groups in P2/P2'. The ortho- and
      meta-fluorinated P1/P1'-benzyloxy side groups proved to have the most
      cytopathogenic effects compared with the nonsubstituted analog and related C2
      symmetric diol-based inhibitors. The different fluoro-substitutions are well
      accommodated in the protease S1/S1' subsites, as observed by an increase in
      favorable Van der Waals contacts and surface area buried by the inhibitors. These
      data will be used in the development of potent inhibitors with different
      pharmacokinetic profiles towards resistant protease mutants.

PMID- 15560802
TI  - The effectiveness of a toothpaste containing triclosan and polyvinyl-methyl ether
      maleic acid copolymer in improving plaque control and gingival health: a
      systematic review.
AB  - OBJECTIVE: To compare the effectiveness of triclosan/copolymer and fluoride
      dentifrices in improving plaque control and gingival health. SEARCH STRATEGY: We
      searched the Cochrane Controlled Trials Register, MEDLINE (1986 to March 2003)
      and EMBASE (1986 to March 2003). Personal files and the reference lists of all
      articles were checked for further studies. SELECTION CRITERIA: Trials were
      selected if they met the following criteria: random allocation of participants;
      participants were adults with plaque and gingivitis; unsupervised use of
      dentifrices for at least 6 months; and primary outcomes - plaque and gingivitis
      after 6 months. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted information. For each plaque and gingivitis index, the mean differences
      for each study were pooled as weighted mean differences (WMDs) with the
      appropriate 95% confidence intervals (CIs) using the random effect models. MAIN
      RESULTS: Sixteen trials provided data for the meta-analysis. The
      triclosan/copolymer dentifrice significantly improved plaque control compared
      with a fluoride dentifrice, with a WMD of -0.48 (95% CI: -0.64 to -0.32) for the
      Quigley-Hein index and WMD of -0.15 (95% CI: -0.20 to -0.09) for the plaque
      severity index. When compared with a fluoride dentifrice, the triclosan/copolymer
      dentifrice significantly reduced gingivitis with WMDs -0.26 (95% CI: -0.34 to 
      0.18) and -0.12 (95% CI: -0.17 to -0.08) for the Loe and Silness index and
      gingivitis severity index, respectively.

PMID- 15560803
TI  - Methods of detection of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis and Tannerella forsythensis in periodontal microbiology, with special
      emphasis on advanced molecular techniques: a review.
AB  - BACKGROUND: Certain specific bacterial species from the subgingival biofilm have
      demonstrated aetiological relevance in the initiation and progression of
      periodontitis. Among all the bacteria studied, three have shown the highest
      association with destructive periodontal diseases: Actinobacillus
      actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Tannerella
      forsythensis (Tf). Therefore, the relevance of having accurate microbiological
      diagnostic techniques for their identification and quantification is clearly
      justified. AIM: To evaluate critically all scientific information on the
      currently available microbial diagnostic techniques aimed for the identification
      and quantification of Aa, Pg and Tf. SUMMARY: Bacterial culturing has been the
      reference diagnostic technique for many years and, in fact, most of our current
      knowledge on periodontal microbiology derives from cultural data. However, the
      advent of new microbial diagnostics, mostly based on immune and molecular
      technologies, has not only highlighted some of the shortcomings of cultural
      techniques but has also allowed their introduction as easy and available adjunct
      diagnostic tools to be used in clinical research and practice. These
      technologies, mostly polymerase chain reaction (PCR), represent a field of
      continuous development; however, we still lack the ideal diagnostic to study the
      subgingival microflora. Qualitative PCR is still hampered by the limited
      information provided. Quantitative PCR is still in development; however, the
      promising early results reported are still hampered by the high cost and the
      equipment necessary for the processing. CONCLUSION: Quantitative PCR technology
      may have a major role in the near future as an adjunctive diagnostic tool in both
      epidemiological and clinical studies in periodontology. However, culture
      techniques still hold some inherent capabilities, which makes this diagnostic
      tool the current reference standard in periodontal microbiology.

PMID- 15560804
TI  - Subgingival plaque microbiota in Saudi Arabians after use of miswak chewing stick
      and toothbrush.
AB  - BACKGROUND: The chewing stick, the miswak, is used in many developing countries
      as the traditional means for oral hygiene. It is prepared from the roots, twigs
      and stem of Salvadora persica or other alternative local plants. OBJECTIVES: To
      compare the effects of the chewing stick miswak (from S. persica) and toothbrush
      on subgingival plaque microflora among Saudi Arabian individuals. Further, to
      investigate whether components extracted from S. persica may interfere with the
      subgingival plaque micro-organisms. MATERIAL AND METHODS: Fifteen healthy Saudi
      Arabian male volunteers aged 21-36 years were included in a single-blind,
      randomized cross-over study. The participants were taught how to use each device
      properly. Plaque sampling for DNA test was performed at the baseline, 1 week
      after professional tooth cleaning, and after 3 weeks of either miswak or
      toothbrush use. Identification and quantification of microbial species were
      performed by the checkerboard method, using whole genomic, digoxigenin-labelled
      DNA probes. Inhibition zones around miswak were examined on agar plates with
      Actinobacillus actinomycetemcomitans and the leukotoxicity of this bacterium was
      analyzed in a bioassay with macrophages+/-extracts of miswak. RESULTS: Miswak and
      toothbrushing had a similar influence on the levels of the subgingival
      microbiota. However, A. actinomycetemcomitans was significantly more reduced by
      miswak (p<0.05) than by toothbrushing. These results were supported by our in
      vitro results which, indicated that extracts from S. persica might interfere with
      the growth and leukotoxicity of A. actinomycetemcomitans. CONCLUSIONS: In
      contrast to toothbrush use, miswak use significantly reduced the amount of A.
      actinomycetemcomitans in the subgingival plaque.

PMID- 15560805
TI  - Quantitative real-time polymerase chain reaction based on single copy gene
      sequence for detection of periodontal pathogens.
AB  - OBJECTIVE: To develop a method for quantification of Actinobacillus
      actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Tannerella
      forsythensis (Tf) from subgingival plaque samples based on TaqMan real-time
      polymerase chain reaction (PCR) technology. MATERIAL AND METHODS: Bacterial cells
      from these species were obtained after culturing reference strains and were
      counted microscopically. Cellular suspensions in Tris-EDTA buffer were used for
      DNA extraction after boiling for 20 min. Primers for PCR were selected from
      sequences of the LktC (Aa), Arg-gingipain (Pg) and BspA antigen (Tf) genes in
      order to yield amplicons below 100 bp. TaqMan-based real-time PCR was adjusted to
      quantify each species separately. Cycle threshold (C(T)) values were calculated
      for each species according to the initial number of copies. A reliability
      analysis was carried out using intra-class correlation coefficients (ICCs) with a
      two-way random effects model. RESULTS: A high sensitivity and specificity was
      obtained for the detection of the three bacterial species. The TaqMan real-time
      PCR technology yielded a good repeatability in the obtained cycle threshold
      (C(T)) values for each initial number of copies, demonstrating coefficients of
      variation below 5% for each bacteria. The reproducibility of the technique was
      also demonstrated by the high ICCs (>0.98; p<0.00001) obtained for each bacteria
      with and without the addition of subgingival plaque. CONCLUSION: A novel
      diagnostic method based on TaqMan real-time PCR was developed for the
      quantification of Aa, Pg and Tf. It has demonstrated good sensitivity and
      repeatability on pure cultures. Its diagnostic utility should be demonstrated in
      subgingival plaque samples.

PMID- 15560806
TI  - Quantitative real-time polymerase chain reaction versus culture: a comparison
      between two methods for the detection and quantification of Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythensis in
      subgingival plaque samples.
AB  - OBJECTIVE: The purpose of this investigation was to validate a real-time
      quantitative polymerase chain reaction (PCR) assay in identifying and quantifying
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Tannerella
      forsythensis from subgingival plaque samples taken from subjects with different
      periodontal conditions, when compared with conventional cultural procedures.
      PATIENTS AND METHODS: Ninety-two adult subjects participated in this study, 32
      with periodontitis, 30 with gingivitis and 30 healthy. A pooled subgingival
      sample was obtained from every patient. Culturing procedures were carried out
      using standard techniques. For real-time PCR analysis, primers were selected from
      sequences of the LktC (A. actinomycetemcomitans), Arg-gingipain (P. gingivalis)
      and BspA antigen (T. forsythensis) genes. Contingency tables were constructed to
      compare the qualitative results, while quantitative data were evaluated by paired
      t-test. RESULTS: A. actinomycetemcomitans was the least frequently recovered
      species with both techniques. Prevalence of P. gingivalis was low in healthy
      patients, increased in gingivitis and peaked in periodontitis patients. The
      frequency of detection of T. forsythensis showed marked differences between
      culture and PCR, although the same tendency of an increase in prevalence from
      health to gingivitis and to periodontitis was observed with both methods.
      Contingency tables demonstrated a good level of agreement between PCR and culture
      procedures for A. actinomycetemcomitans and P. gingivalis, especially in
      periodontitis patients. P. gingivalis culture counts were significantly higher
      than those obtained by PCR. The opposite was true for T. forsythensis, and
      statistically significant higher counts were obtained by PCR for gingivitis and
      periodontitis patients. CONCLUSION: This study demonstrated a good agreement
      between the quantitative PCR technology and the culture procedure. The high
      sensitivity and specificity of the quantitative PCR technology justify its use in
      epidemiological studies and as an adjunct in clinical diagnosis of periodontal
      patients.

PMID- 15560807
TI  - Scaling and root planing, systemic metronidazole and professional plaque removal
      in the treatment of chronic periodontitis in a Brazilian population. I. clinical
      results.
AB  - OBJECTIVE: The current investigation evaluated the clinical effects of scaling
      and root planing (SRP) alone or in combination with systemic metronidazole and/or
      repeated professional removal of supragingival plaque in subjects with chronic
      periodontitis. METHODS: Fourty-four adult subjects (mean age: 45+/-6 years) with
      periodontitis were randomly assigned to four treatment groups; a control (C,
      n=10) that received SRP and placebo and three test groups treated as follows:
      Test 1 (T1) (n=12) received SRP and metronidazole (400 mg t.i.d., M) for 10 days;
      Test 2 (T2) (n=12) received SRP, weekly professional supragingival plaque removal
      for three months (professional cleaning (PC)) and placebo; and Test 3 (T3) (n=10)
      received SRP, M and PC. Pocket depth (PD), attachment level (AL), bleeding on
      probing (BOP) and presence of visible plaque and suppuration were measured at six
      sites per tooth at baseline and at 90 days post-therapy. Significance of
      differences over time was determined using the Wilcoxon test, and among groups
      using ancova. RESULTS: A reduction in full-mouth mean clinical parameters was
      observed at 90 days after all therapies. Sites with baseline PD<4 mm showed an
      increase in mean PD in the control group and in mean AL in all treatment groups.
      Sites with baseline PD of 4-6 mm in subjects who received PC as part of therapy
      (T2, T3) showed a marked reduction in PD, AL and in the % of sites with BOP.
      Subjects who received metronidazole (T1 and T3) showed the best clinical response
      at sites with an initial PD of >6 mm. The major clinical benefit occurred when
      the combination of SRP, M and PC was used. Group T3 showed the least attachment
      loss in initially shallow pockets. This group also exhibited the greatest
      reduction in the % of sites with BOP and suppuration as well as in mean PD and AL
      at sites with baseline PD>4 mm. CONCLUSION: The data suggest a significant
      clinical benefit in combining SRP, systemic metronidazole and weekly professional
      supragingival plaque removal for the treatment of chronic periodontitis.

PMID- 15560808
TI  - Bone level change at implant-supported fixed partial dentures with and without
      cantilever extension after 5 years in function.
AB  - OBJECTIVE: The aim of this study was to retrospectively analyze whether the
      inclusion of cantilever extensions increased the amount of marginal bone loss at
      free-standing, implant-supported, fixed partial dentures (FPDs) over a 5-year
      period of functional loading. MATERIAL AND METHODS: The patient material
      comprised 45 periodontally treated, partially dentate patients with a total of 50
      free-standing FPDs supported by implants of the Astra Tech System. Following FPD
      placement (baseline) the patients were enrolled in an individually designed
      supportive care program. A set of criteria was collected at baseline to
      characterize the FPDs. The primary outcome variable was change in peri-implant
      bone level from the time of FPD placement to the 5-year follow-up examination.
      The comparison between FPDs with and without cantilevers was performed at three
      levels: FPD level, implant level, and surface level. Bivariate analysis was
      performed by the use of the Mann-Whitney U-test and stepwise regression analysis
      was utilized to evaluate the potential influence of confounding factors on the
      change in peri-implant bone level. RESULTS: The overall mean marginal bone loss
      for the implant-supported FPDs after 5 years in function was 0.4 mm (SD, 0.76).
      The bone level change at FPDs placed in the maxilla was significantly greater
      than that for FPDs in the mandible (0.6 versus 0.2 mm; p<0.05). No statistically
      significant differences were found with regard to peri-implant bone level change
      over the 5 years between FPDs with and without cantilevers at any of the levels
      of comparisons. The multivariate analysis revealed that the variables jaw of
      treatment and smoking had a significant influence on peri-implant bone level
      change on the FPD level, but not on the implant or surface levels. The model
      explained only 10% of the observed variance in the bone level change. CONCLUSION:
      The study failed to demonstrate that the presence of cantilever extensions in an
      FPD had an effect on peri-implant bone loss.

PMID- 15560809
TI  - The plaque-removing efficacy of a finger brush (I-Brush).
AB  - OBJECTIVE: The purpose of the present study was to test the effectiveness of a
      finger toothbrush (I-Brush) in removing plaque compared with a flat-trimmed
      manual toothbrush. MATERIAL AND METHODS: For this study, 37 subjects were
      selected, without previous experience of the use of the I-Brush. Each subject
      received a finger brush (I-Brush), a manual toothbrush (Butler GUM 311), two
      written brushing instructions for both types of brushes, and a brush calendar.
      Subjects were given a period of 3 weeks to become familiar with the two types of
      brushes. During this period, the subjects were instructed to use the two types of
      brushes on alternate days. The brush calendar helped as a reminder and served to
      ensure compliance. No instructions regarding brushing time or frequency of
      brushing were given to the subjects, except that they should conform to their
      usual oral habits. After 3 weeks, all subjects were asked to abstain from oral
      hygiene procedures for 48 h prior to the experiment. In this experiment, the
      amount of dental plaque was scored by a trained examiner. The examiner (N.A.M.R.)
      used the modified Silness & Loe (1964) plaque index at six sites per tooth. After
      scoring, each subject received a new finger brush and a new manual toothbrush.
      The subjects brushed according to a split mouth protocol. Two contra-lateral
      quadrants were chosen randomly and were brushed with one randomly chosen brush
      and the two opposing contra-lateral quadrants with the alternate brush. The
      brushing was performed under supervision in front of a mirror. The available time
      for brushing was 2 min. for the entire dentition. Finally, the remaining plaque
      was scored again. RESULTS: The overall reduction in plaque was 79% for the manual
      toothbrush and 62% for the finger brush. The plaque removing efficacy of the
      finger brush was poorest at the approximal vestibular surfaces (55% plaque
      reduction) compared with the manual toothbrush (77% plaque reduction).
      CONCLUSION: The plaque reduction of the finger brush is not an acceptable
      alternative to the use of a regular manual toothbrush.

PMID- 15560810
TI  - Clinical study to compare the effectiveness of a test whitening toothpaste with a
      commercial whitening toothpaste at inhibiting dental stain.
AB  - AIMS: A single centre, randomised single-blind, three-way crossover study was
      performed, to compare the effect of an experimental test toothpaste with a
      commercially available whitening toothpaste and water control at inhibiting
      extrinsic stain promoted by repeated chlorhexidine/tea rinses. METHODS: This
      study used 23 subjects. During the week before the study the subjects received a
      prophylaxis to remove all staining, plaque and calculus deposits. On the Monday
      of the following week subjects returned to the clinic to receive their rinses and
      to check their dentition was stain free. Under direct supervision at both 09:00
      and 13:00 hours they rinsed with either a toothpaste slurry or water control that
      was repeated daily up to and including the following Thursday. Additionally from
      the Monday to the Thursday each subject rinsed with a 0.2% chlorhexidine
      mouthrinse, immediately followed by a rinse with a warm black tea solution. This
      cycle was repeated hourly eight times throughout the day and on the following
      days until the Friday. Throughout this period volunteers omitted all other forms
      of oral hygiene except rinsing with the chlorhexidine mouthwash. On the Friday
      the level of stain on the teeth and dorsum of tongue was assessed using the
      Lobene stain index for both stain area and intensity. At the end of each trial
      period each subject received a thorough prophylaxis to remove all plaque,
      calculus and staining before starting the second and third period of the study.
      RESULTS: As expected appreciable amounts of extrinsic stain accumulated on the
      teeth over each study period. The amount of stain following use of the
      toothpastes and water control was least with the experimental toothpaste,
      followed by water control and lastly the commercial whitening paste. For all
      sites combined there was evidence that the experimental paste was significantly
      superior to both the commercial paste and water control at reducing stain area
      (p<0.001), a product of stain area and intensity (p<0.001 and 0.05, respectively)
      but not stain intensity (p>0.05). CONCLUSIONS: In this stain-prevention model the
      use of an experimental paste showed a significant reduction in stain accumulation
      on the teeth compared with a (placebo) negative water control and a commercially
      available whitening paste. As such the experimental paste would be expected to be
      of benefit in controlling extrinsic dental staining.

PMID- 15560811
TI  - Healing, post-operative morbidity and patient perception of outcomes following
      regenerative therapy of deep intrabony defects.
AB  - AIM: This prospective multicenter randomized controlled clinical trial was
      designed to compare the clinical outcomes of papilla preservation flap surgery
      with or without the application of enamel matrix derivatives (EMD). This article
      reports on early healing events, post-operative morbidity and patient perceptions
      of the surgical outcomes. MATERIAL AND METHODS: One hundred and seventy-two
      patients with advanced chronic periodontitis and at least one intrabony defect of
      > or =3 mm were recruited in 12 centres in seven countries (European Research
      Group on Periodontology (ERGOPERIO)). Papilla preservation flaps were used to
      obtain access and primary closure. After debridement, and root conditioning, EMD
      was applied in the test subjects, and omitted in the controls. Healing was
      monitored 1, 2, 3, 4, 6 and 12 weeks after surgery. During the first 12 weeks of
      healing, supracrestal soft-tissue density was evaluated with a computer-assisted
      densitometric image analysis system (CADIA) using underexposed radiographs taken
      on a subset of 34 patients. Patient perceptions were evaluated with a
      questionnaire immediately after the procedure, at suture removal 1 week later and
      at 1 year. RESULTS: Subjects reported little intraoperative or post-operative
      pain or discomfort for both test and controls. Twenty-four percent of controls
      and 30% of tests (p=0.64) reported a degree of interference with daily activities
      for an average of 3 and 3.5 days, respectively. Post-surgical edema was noted in
      25% of tests and 28% of controls. Wound dehiscence in the interdental portion of
      the flap was uncommon (14% of tests and 12% of controls at week 1) and of limited
      size. Root sensitivity was the most frequent post-operative adverse event: it
      affected 45% of test and 35% of controls (p=0.55). Up to 6 weeks post
      operatively, soft-tissue densities were significantly higher in subjects treated
      with EMD with respect to controls. One year after completion of the surgery,
      patients reported high levels of satisfaction with the outcomes. The most
      frequently reported benefits included the ability to preserve a tooth/dentition
      and to maintain/improve chewing ability. The cost and need for frequent follow
      ups were cited as significant drawbacks. CONCLUSIONS: This study portrayed the
      early healing events, pain, discomfort and adverse events of papilla preservation
      flap surgery and the 1-year patient perceptions of the benefits and disadvantages
      of periodontal surgery in intrabony defects. Earlier gains in soft-tissue density
      were observed following application of EMD. In terms of patient-centered
      outcomes, however, both procedures performed in a similar manner.

PMID- 15560812
TI  - Dental nomograms for benchmarking based on the study of health in Pomerania data
      set.
AB  - AIM: Benchmarking is a means of setting goals or targets. On an oral health
      level, it denotes retaining more teeth and/or improving the quality of life. The
      goal of this pilot investigation was to assess whether the data generated by a
      population-based study (SHIP 0) can be used as a benchmark data set to
      characterize different practice profiles. MATERIAL AND METHODS: The data
      collected in the population-based study SHIP (n=4310) in eastern Germany were
      used to generate nomograms of tooth loss, attachment loss, and probing depth. The
      nomograms included twelve 5-year age strata (20-79 years) presented as quartiles,
      and additional percentiles of the dental parameters for each age group. Cross
      sectional data from a conventional dental office (n=186) and from a
      periodontology unit (n=130, Greifswald) in the study region as well as
      longitudinal data set of a another periodontology unit (n=135, Kiel) were
      utilized in order to verify whether the given practice profile was accurately
      reflected by the nomogram. RESULTS: In terms of tooth loss, the data from the
      conventional dental office agree with the median from the nomogram. For
      attachment loss and probing depth, some age groups yielded slight but not uniform
      deviations from the median. Cross-sectional data from the periodontology unit
      Greifswald showed attachment loss higher than the median in younger but not in
      older age groups. The probing depth was uniformly less than the median and tended
      toward the 25th percentile with increasing age. The longitudinal data of the Unit
      of Periodontology in Kiel showed a pronounced trend towards higher percentiles of
      residual teeth, meaning that the patients retained more teeth. CONCLUSION: The
      profile of the Pomeranian dental office does not deviate noticeably from the
      population-based nomograms. The higher attachment loss of the Unit of
      Periodontology in Greifswald in younger age strata clearly reflects their
      selection because of periodontal disease; the combination of higher attachment
      loss and decreased probing depth may reflect the success of the treatment. The
      tendency of attachment loss towards the median with increasing age may indicate
      that the Unit of Periodontology in Greifswald does not fulfill its function as a
      special care unit in the older subjects. The longitudinal data set of the Unit of
      Periodontology in Kiel impressively reflects the potential of population-based
      data sets as a means for benchmarking. Thus, nomograms can help to determine the
      practice profile, potentially yielding benefits for the dentist, health insurance
      company, or--as in the case of the special care unit--public health research.

PMID- 15560813
TI  - A methodology using subjective and objective measures to compare plaque
      inhibition by toothpastes.
AB  - OBJECTIVES: Plaque scoring usually employs subjective indices. The aim was to
      compare plaque inhibition of three toothpastes using two objective and one
      subjective measures of plaque. MATERIAL AND METHODS: Formulations were: (1) an
      experimental anti-plaque paste (test); (2) an experimental paste (minus active or
      negative control); and (3) a proprietary anti-plaque toothpaste product (positive
      control). The study was a blind, randomised crossover design using a 4-day, no
      tooth brushing, plaque regrowth model and involving 22 healthy subjects. After
      baseline plaque removal, subjects rinsed twice a day with slurries of the
      allocated paste. On day 5, plaque was scored by index, wet weight and optical
      density of extracted disclosing solution from the plaque (stain intensity).
      RESULTS: All data showed the same pattern. There were highly significant subject
      and treatment effects but not period effects. The positive control was highly
      significantly more effective in plaque control than the test and minus active
      experimental formulations, which in turn were not significantly different from
      each other. There were strong and significant correlations between pairs of
      scoring methods particularly wet weight and stain intensity. CONCLUSION: The use
      of objective methods of plaque alongside conventional subjective indices provided
      convincing evidence for increased discriminatory power in a study comparing
      plaque inhibition by toothpastes.

PMID- 15560814
TI  - Alterations of gene expression in human neutrophils induced by smoking cessation.
AB  - OBJECTIVE: The purpose of the present study was to investigate the effect of
      smoking cessation on the peripheral neutrophil mRNA expression levels for
      inflammatory cytokines, chemokine, growth factor and matrix metalloproteinase
      (MMP). MATERIAL AND METHODS: Sixteen male smokers (aged 22-39 [25.3+/-4.0]
      years), with no clinical signs of periodontal and systemic diseases, were
      recruited. The experiment was performed before (baseline) and at 1, 4 and 8 weeks
      after smoking cessation. The status of smoking and smoking cessation was verified
      by exhaled carbon monoxide (CO) concentration and serum cotinine concentration.
      Neutrophils were isolated from each subjects' peripheral blood, then the cell was
      stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP). The mRNA
      expression levels for interleukin (IL)-1 beta, IL-8, tumor necrosis factor (TNF)
      alpha, vascular endothelial growth factor (VEGF) and MMP-8 were analyzed by
      semiquantitative reverse transcription-polymerase chain reactions. The same
      experiment was performed on 11 non-smoking controls (four female and seven male),
      aged 23-27 (24.4+/-1.2) years. RESULTS: Eleven of 16 smokers successfully
      completed smoking cessation for 8 weeks. At 1 day after smoking cessation, there
      was a statistically significantly lower CO concentration than at baseline
      (p<0.01). Also, cotinine concentration markedly decreased at the second
      measurement, which was taken at 1 week. All of the analyzed mRNA expression
      levels of neutrophils from smokers were statistically significantly lower than
      that in non-smokers (p<0.01: IL-1 beta, IL-8, VEGF; p<0.05: TNF-alpha, MMP-8).
      The MMP-8 mRNA levels were statistically significantly increased at 8 weeks after
      smoking cessation compared with the baseline (p<0.05). Although the other mRNA
      expression levels were also elevated gradually from the baseline, they did not
      reach the statistically significant levels at 8 weeks after smoking cessation.
      CONCLUSION: The results showed that the neutrophil transcript levels in smokers
      were generally lower than those in non-smokers, which could be related to an
      impairment of neutrophils by smoking effects. The significant increase of MMP-8
      mRNA levels were associated with the effects of smoking cessation, while recovery
      of the other mRNA levels seemed to require a bit longer period beyond 8 weeks
      after smoking cessation.

PMID- 15560815
TI  - In vitro studies on controlled-release cellulose acetate films for local delivery
      of chlorhexidine, indomethacin, and meloxicam.
AB  - BACKGROUND: Delivery of medications into periodontal pockets to suppress or
      eradicate the pathogenic microbiota or modulate the inflammatory response,
      thereby limiting periodontal tissue destruction, has attracted significant
      interest with the purpose of effective periodontal treatment. However, no study
      has previously attempted to develop a controlled-release formulation of anti
      inflammatory agents to be used in the field of periodontology. The aim of the
      present study was to examine the in vitro release profile of chlorhexidine
      gluconate, indomethacin, and meloxicam from cellulose acetate films. METHODS:
      Cellulose acetate films containing chlorhexidine gluconate, indomethacin, and
      meloxicam were prepared and cut in a form to fit to the periodontal pocket
      anatomy. The release of active agents was studied in 10 ml artificial saliva at
      37 degrees C. Apparatus Vibrax was used at 150 r.p.m. Determinations were carried
      out spectrophotometrically and the release profiles were plotted as a function of
      time. RESULTS: The formulations showed two different release patterns for a total
      observation period of approximately 120 h. When the formulations of the three
      active agents were compared, the release patterns of meloxicam and chlorhexidine
      gluconate were found to be similar, while the indomethacin-containing formulation
      exhibited the fastest release rate. CONCLUSIONS: As a conclusion, cellulose
      acetate may be a suitable inert material for obtaining a prolonged local release
      of various anti-inflammatory agents like meloxicam. Further in vitro and in vivo
      studies are required before starting clinical applications of these controlled
      release formulations of anti-inflammatory agents.

PMID- 15560816
TI  - The clinical course of chronic periodontitis.
AB  - AIM: The purpose of this study was to assess the long-term influence of gingival
      inflammation on tooth loss. MATERIAL AND METHODS: The data originated from a 26
      year longitudinal study of Norwegian males, who practiced adequate daily oral
      home care and received "state-of-the-art" dental care. The initial examination in
      1969 included 565 individuals aged between 16 and 34 years. Subsequent
      examinations took place in 1971, 1973, 1975, 1981, 1988 and 1995. Thus, the study
      covers the age range of 16-59 years. The teeth were divided into three tooth
      groups (I-III) reflecting the history of inflammation of the surrounding gingiva
      (gingival index (GI) scores) over 26 years: (I) teeth with surrounding gingival
      units scoring a minimum of one site with GI=0 and a maximum of three sites with
      GI=1, (II) teeth with surrounding gingival units scoring a minimum of one site
      with GI=1 and a maximum of three sites with GI=2 over the observation periods and
      (III) teeth with surrounding gingival units always scoring a minimum of GI=2
      (bleeding on probing) at all sites over the observation period. RESULTS: At
      baseline (1969), out of possible 15,820 teeth (565 x 28), 15,383 teeth were
      present. Four hundred and thirty-seven teeth had already been missing for unknown
      reasons. By 1995, 13,159 teeth were reexamined, i.e. over the 26-year observation
      period only 126 (0.95%) teeth were lost. Only 16 (0.28%) of 5793 teeth belonging
      to GI-Severity Group I were lost. In the GI-Severity Group II, however, 78
      (2.28%) out of 3348 teeth were lost, and 13 (11.21%) of 103 teeth with GI
      Severity Group III were lost. Teeth with GI-Severity Group III yielded an odds
      ratio for tooth loss that was 46 times higher than that of teeth with GI-Severity
      Group I, and five times higher than that of teeth with GI-Severity Group II over
      26 years. Furthermore, teeth with the GI-Severity Group II had a nine times
      higher risk for tooth loss than teeth with the GI-Severity Group I. The GI
      Severity Group I retained 99.5% of the teeth after a tooth age of 51 years. The
      GI-Severity Group II retained 93.8% of the teeth after a tooth age of 50 years.
      However, in the GI-Severity Group III, 63.4% of the teeth were retained for a
      tooth age of 47 years. CONCLUSIONS: Teeth surrounded with inflammation-free
      gingival tissues were maintained for a tooth age of 51 years, while teeth
      consistently surrounded with inflamed gingivae yielded a 46-times higher risk to
      be lost. Only two-thirds of such teeth were maintained throughout the 26-year
      observation period. This documents the role of gingival inflammation as a risk
      factor for future tooth loss.

PMID- 15560817
TI  - Comparative effects of different chlorhexidine mouth-rinse formulations on
      volatile sulphur compounds and salivary bacterial counts.
AB  - AIM: To compare five different commercial mouth rinses with chlorhexidine (CHX)
      with respect to their anti-halitosis effect and anti-microbial activity on
      salivary bacterial counts, following a standardised research protocol. And
      secondly, to validate the study model proposed in the evaluation of patients
      suffering from halitosis. PATIENTS AND METHODS: Ten volunteers, with a healthy
      oral status, were enrolled in a double-blind, cross-over design, using sterile
      saline as negative control and five CHX-containing mouth rinses: 0.12% CHX alone
      (CHX+NO), plus alcohol (CHX+ALC), plus 0.05% cetylpiridinium chloride (CHX+CPC),
      plus sodium fluoride (CHX+NaF), and 0.05% CHX plus 0.05% CPC, plus 0.14% zinc
      lactate (CHX+Zn). The levels of whole-mouth volatile sulphur compounds (VSCs)
      were measured by means of a sulphide monitor at baseline, 1 and 5 h after rinsing
      with the assigned product. Baseline measurements also included an organoleptic
      assessment and the recording of the tongue-coating index. Aerobic and anaerobic
      salivary bacterial counts were also obtained by collecting unstimulated saliva
      samples at the same evaluation times, and processed by culturing techniques.
      Analysis of variance was used to evaluate whether significant differences existed
      among groups, at each evaluation point, or in changes between evaluations.
      RESULTS: No significant differences were detected at baseline, with VSC levels
      ranging between 190 and 227 parts per billion (p.p.b.) After rinsing, VSC levels
      were reduced with all products (except saline), after 1 h. Significant
      differences at 1 h were detected (p=0.04), corresponding to a lower amount of
      p.p.b. (109) in (CHX+Zn) as compared with the other groups (except CHX+NO). At 5
      h, VSC levels were lower for CHX+CPC and CHX+Zn (155 and 169, respectively),
      while the other groups showed levels higher than 220 p.p.b. With respect to
      aerobic salivary bacterial counts, CHX+CPC demonstrated the lowest percentage of
      survival (6% after 1 h and 18% after 5 h). For anaerobic bacterial counts, again
      CHX+CPC demonstrated the lowest percentage of survival (10% at 1 h and 23% at 5
      h), together with CHX+ALC (18% of survival at 5 h). However, salivary counts and
      VSCs were only significantly correlated at baseline, but not after treatment.
      CONCLUSION: Important differences can be expected from different CHX
      formulations, in relation to both their anti-halitosis effect and anti-microbial
      activity in saliva. Formulations that combine CHX and CPC achieved the best
      results, and a formulation combining CHX with NaF resulted in the poorest.

PMID- 15560818
TI  - Genomes back-to-back: when sequencing race is a good thing.

PMID- 15560819
TI  - Influence of form IA RubisCO and environmental dissolved inorganic carbon on the
      delta13C of the clam-chemoautotroph symbiosis Solemya velum.
AB  - Many nutritive symbioses between chemoautotrophic bacteria and invertebrates,
      such as Solemya velum, have delta(13)C values of approximately -30 to -35%,
      considerably more depleted than phytoplankton. Most of the chemoautotrophic
      symbionts fix carbon with a form IA ribulose 1,5-bisphosphate carboxylase
      (RubisCO). We hypothesized that this form of RubisCO discriminates against
      (13)CO(2) to a greater extent than other forms. Solemya velum symbiont RubisCO
      was cloned and expressed in Escherichia coli, purified and characterized. Enzyme
      from this recombinant system fixed carbon most rapidly at pH 7.5 and 20-25
      degrees C. Surprisingly, this RubisCO had an epsilon-value (proportional to the
      degree to which the enzyme discriminates against (13)CO(2)) of 24.4 per thousand,
      similar to form IB RubisCOs, and higher than form II RubisCOs. Samples of
      interstitial water from S. velum's habitat were collected to determine whether
      the dissolved inorganic carbon (DIC) could contribute to the negative delta(13)C
      values. Solemya velum habitat DIC was present at high concentrations (up to
      approximately 5 mM) and isotopically depleted, with delta(13)C values as low as
      approximately -6%. Thus environmental DIC, coupled with a high degree of isotopic
      fractionation by symbiont RubisCO likely contribute to the isotopically depleted
      delta(13)C values of S. velum biomass, highlighting the necessity of considering
      factors at all levels (from environmental to enzymatic) in interpreting stable
      isotope ratios.

PMID- 15560820
TI  - Biofilm susceptibility to metal toxicity.
AB  - This study compared bacterial biofilm and planktonic cell susceptibility to metal
      toxicity by evaluating the minimum inhibitory concentration (MIC), the planktonic
      minimum bactericidal concentration (MBC), and minimum biofilm eradication
      concentration (MBEC) using the MBEC device. In total, 17 metal cations and
      oxyanions, chosen to represent groups VIB to VIA of the periodic table, were each
      tested on biofilm and planktonic cultures of Escherichia coli JM109,
      Staphylococcus aureus ATCC 29213, and Pseudomonas aeruginosa ATCC 27853. In
      contrast to control antibiotic assays, where biofilm cultures were 2 to 64 times
      less susceptible to killing than logarithmically growing planktonic bacteria,
      metal compounds killed planktonic and biofilm cultures at the same concentration
      in the vast majority of combinations. Our data indicate that, under the
      conditions reported, growth in a biofilm does not provide resistance to bacteria
      against killing by metal cations or oxyanions.

PMID- 15560821
TI  - Composition of freshwater bacterial communities associated with cyanobacterial
      blooms in four Swedish lakes.
AB  - The diversity of freshwater bacterioplankton communities has not been extensively
      studied despite their key role in foodwebs and the cycling of carbon and
      associated major elements. In order to explore and characterize the composition
      of bacterioplankton associated with cyanobacterial blooms, large 16S rRNA clone
      libraries from four lakes experiencing such blooms were analysed. The four
      libraries contained 1461 clones, of which 559 were prokaryotic sequences of non
      cyanobacterial origin. These clones were classified into 158 operational
      taxonomic units affiliated mainly with bacterial divisions commonly found in
      freshwater systems, e.g. Proteobacteria, Bacteriodetes, Actinobacteria,
      Verrucomicrobia and Planctomycetes. Richness and evenness of non-cyanobacterial
      clones were similar to other clone libraries obtained for freshwater
      bacterioplankton, suggesting that bacterial communities accompanying
      cyanobacterial blooms are as diverse as non-bloom communities. Many of the
      identified operational taxonomic units grouped with known freshwater clusters but
      the libraries also contained novel clusters of bacterial sequences that may be
      characteristic for cyanobacterial blooms. About 25% of the operational taxonomic
      units were detected in more than one lake. Even so, 16S rRNA heterogeneity
      analysis demonstrated large differences in community composition between lakes
      regardless of their similar characteristics and close proximity. Hence even the
      similar environmental conditions created by different cyanobacterial blooms may
      foster very dissimilar bacterial communities, which could indicate that the
      genetic diversity in lake bacteria have been underestimated in the past.

PMID- 15560822
TI  - Isolation and characterization of soybean-associated bacteria and their potential
      for plant growth promotion.
AB  - Endophytic and epiphytic bacteria were isolated from two soybean cultivars
      (Foscarin and Cristalina). Significant differences were observed in bacterial
      population densities in relation to season of isolation, soybean growth phase and
      the tissues from which the isolates were obtained. The isolates were identified
      by partial 16S rDNA sequence analysis, with most of the isolates belonging to the
      Pseudomonaceae, Burkholderiacea and Enterobacteriaceae groups. The potential of
      the isolates for plant growth promotion was evaluated by screening for
      indoleacetic acid (IAA) production and mineral phosphate solubilization; 34% of
      endophytic bacteria produced IAA and 49% were able to solubilize mineral
      phosphate whereas only 21% of epiphytic bacteria produced IAA although 52% were
      able to solubilize mineral phosphate. A high frequency of IAA producing isolates
      occurred in the early ripening Foscarin cultivar whereas a high percentage of
      phosphate solubilizing isolates were obtained from plants in the initial
      development stage (V6). We also found that 60% of endophytic and 69% of epiphytic
      isolates that produced IAA and solubilized mineral phosphate were also able to
      fix nitrogen in vitro. The soybean-associated bacteria showing characteristics
      related to plant growth promotion were identified as belonging to the genera
      Pseudomonas, Ralstonia, Enterobacter, Pantoea and Acinetobacter.

PMID- 15560823
TI  - Phylogenetic characterization of Legionella-like endosymbiotic X-bacteria in
      Amoeba proteus: a proposal for 'Candidatus Legionella jeonii' sp. nov.
AB  - The X-bacteria which initiated organismic association with the D strain of Amoeba
      proteus in 1966 as parasites have changed to obligate endosymbionts on which the
      host depends for survival. Owing to the difficulty in cultivating the bacteria in
      vitro, the identity of X-bacteria has not been determined. As the life cycle of X
      bacteria is similar to that of Legionella spp. in soil amoebae, we applied the
      polymerase chain reaction method with specific primers aimed at Legionella spp.
      for the detection and cloning of 16S rRNA gene. The identity and intracellular
      localization of the endosymbiont were confirmed by the application of a specific
      fluorescently labelled 16S rRNA-targeted probe. In addition we cloned RNA
      polymerase beta-subunit gene (rpoB) of X-bacteria by genomic library tagging. A
      phylogenetic analysis of the 16S rRNA gene placed the bacterium within a unique
      monophyletic group containing all other members of the genus Legionella.
      Phylogeny from rpoB and mip genes further confirmed the taxonomic context of X
      bacteria to be a Legionella sp. In all three phylogenic analyses, X-bacterium was
      placed apart from Legionella-like amoebal pathogens present in soil amoebae.
      Thus, we propose the name 'Candidatus Legionella jeonii' sp. nov. for the
      endosymbiotic X-bacteria in Amoeba proteus.

PMID- 15560824
TI  - Insights into the genomic basis of niche specificity of Pseudomonas putida
      KT2440.
AB  - A major challenge in microbiology is the elucidation of the genetic and
      ecophysiological basis of habitat specificity of microbes. Pseudomonas putida is
      a paradigm of a ubiquitous metabolically versatile soil bacterium. Strain KT2440,
      a safety strain that has become a laboratory workhorse worldwide, has been
      recently sequenced and its genome annotated. By drawing on both published
      information and on original in silico analysis of its genome, we address here the
      question of what genomic features of KT2440 could explain or are consistent with
      its ubiquity, metabolic versatility and adaptability. The genome of KT2440
      exhibits combinations of features characteristic of terrestrial, rhizosphere and
      aquatic bacteria, which thrive in either copiotrophic or oligotrophic habitats,
      and suggests that P. putida has evolved and acquired functions that equip it to
      thrive in diverse, often inhospitable environments, either free-living, or in
      close association with plants. The high diversity of protein families encoded by
      its genome, the large number and variety of small aralogous families, insertion
      elements, repetitive extragenic palindromic sequences, as well as the mosaic
      structure of the genome (with many regions of 'atypical' composition) and the
      multiplicity of mobile elements, reflect a high functional diversity in P. putida
      and are indicative of its evolutionary trajectory and adaptation to the diverse
      habitats in which it thrives. The unusual wealth of determinants for high
      affinity nutrient acquisition systems, mono- and di-oxygenases, oxido-reductases,
      ferredoxins and cytochromes, dehydrogenases, sulfur metabolism proteins, for
      efflux pumps and glutathione-S-transfereases, and for the extensive array of
      extracytoplasmatic function sigma factors, regulators, and stress response
      systems, constitute the genomic basis for the exceptional nutritional versatility
      and opportunism of P. putida , its ubiquity in diverse soil, rhizosphere and
      aquatic systems, and its renowned tolerance of natural and anthropogenic
      stresses. This metabolic diversity is also the basis of the impressive
      evolutionary potential of KT2440, and its utility for the experimental design of
      novel pathways for the catabolism of organic, particularly aromatic, pollutants,
      and its potential for bioremediation of soils contaminated with such compounds as
      well as for its application in the production of high-added value compounds.

PMID- 15560825
TI  - Isolation and cultivation of Walsby's square archaeon.
AB  - In 1980, A. E. Walsby described a square halophilic archaeon. This archaeon is of
      specific interest because of its unique shape and its abundance in hypersaline
      ecosystems, which suggests an important ecophysiological role. Ever since its
      discovery, the isolation and cultivation of 'Walsby's square archaeon' has been a
      holy grail for many microbiologists working on halophiles. Despite their
      abundance and easy recognition by microscopy, all cultivation attempts have
      failed up to now, marking the organism as one of the unculturables. Cultivation
      of the square archaeon is essential to understand their ecophysiological role and
      the nature of their unique morphologically features. Here, we report the
      isolation and cultivation of the enigmatic square archaeon that we propose to
      name Haloquadratum walsbyi. Pure cultures are easily maintained in simple
      artificial hypersaline media. Initial growth experiments revealed a tolerance to
      high concentrations of MgCl(2) (>2 M) in the presence of 3.3 M NaCl. Fresh
      cultures contained extraordinary large cells (>40 x 40 microm) without any
      visible division structures, ranking them among the largest prokaryotes known to
      date. The genome was estimated to contain approximately three million basepairs.

PMID- 15560828
TI  - Inability to relate tooth forms to face shape and gender.
AB  - This study aimed to examine whether there exists a gender-dependent correlation
      between the inverted face shape and that of the upper central incisor as the
      literature often suggests. Standardized portraits and anterior tooth photographs
      of 204 dental students were made. Standardized enlargements of facial outlines
      and of the upper right incisor outlines were traced. They were classified into
      three different shapes: tapered, ovoid and square-shaped. Ten dentists determined
      twice - with an intervening interval of 3 wk - the gender of the students on the
      basis of the anterior tooth photographs. Tooth and face shapes could be
      classified as tapered (25% and 27%, respectively), ovoid (39% and 41%,
      respectively) or square-shaped (36% and 32%, respectively). A significant
      correlation could be shown between face shape and gender, but not between tooth
      shape and gender. The dentists were correct about the gender of the subjects in
      47 to 59% of all cases. The reproducibility of their judgments varied between 54%
      and 77%. The theory that the tooth shape should correspond to the inverted facial
      shape could therefore not be confirmed. In addition it could be shown that the
      participants were not capable of determining a subject's gender from intraoral
      photographs alone.

PMID- 15560829
TI  - Dental trait anxiety and pain sensitivity as predictors of expected and
      experienced pain in stressful dental procedures.
AB  - A prevailing hypothesis suggests that exaggerated pain expectations in dentally
      anxious and pain-sensitive patients might usually be disconfirmed by a lower
      level of pain experienced during treatment. The present study was conducted to
      investigate whether this contention also holds during stressful dental
      procedures. Patients reporting high and low levels of dental fear and of pain
      sensitivity were compared in their expected and experienced pain and in the
      concordance between the two measures. Participants were 97 patients undergoing
      extraction and root canal treatment. The measuring instruments used were the
      Dental Anxiety Scale (DAS), the Pain Sensitivity Index (PSI), affective and
      sensory pain descriptor scales, and a numerical pain-intensity scale. The results
      demonstrated that patients, in general, expected more pain than they subsequently
      experienced. Subjects with a high DAS score both expected and experienced more
      pain than those with a low DAS score. Within the group of subjects with a high
      DAS score, those indicating high pain sensitivity expected and experienced more
      pain than their counterparts; additionally, only those reporting low pain
      sensitivity disconfirmed their high pain expectancies. The results suggest that
      during stressful dental procedures, patients indicating dental anxiety and pain
      sensitivity above median levels are especially at risk of stabilizing exaggerated
      pain expectations and dental fear.

PMID- 15560830
TI  - Influence of drinking method on tooth-surface pH in relation to dental erosion.
AB  - The aim of this investigation was to study the intraoral pH response on tooth
      surfaces in relation to dental erosion during and after drinking a sugar-free
      cola-type soft drink. Six different methods of drinking were tested in a
      randomized order: holding; short-sipping; long-sipping; gulping; nipping; and
      sucking. Two methods of pH measurement were used in two series of individuals. In
      the first series, pH was measured by using the microtouch method in 12 healthy
      adults at three dental erosion-prone sites: 11 palatally; 11 buccally; and at the
      mesiobuccal cusp tip of 16. In the second series, pH was measured by using the
      telemetric method in 6 healthy individuals, producing continuous recordings of pH
      by means of a glass electrode in a specified approximal area. The two series
      showed similar results, although the telemetric method generally recorded larger
      pH falls. Holding the drink in the mouth before swallowing led to the most
      pronounced pH drop, followed by the long-sipping method. Gulping resulted in only
      a small decrease of pH. No differences among the three intraoral sites were found
      when analyzed by using the microtouch method. The conclusion from this study is
      that the drinking method strongly affects tooth-surface pH and thereby the risk
      for dental erosion. It therefore seems appropriate to include advice on the
      method of drinking in dietary counseling related to dental erosion.

PMID- 15560831
TI  - Comparative fluorescence spectroscopy of root caries lesions.
AB  - In this study, the light-emission properties of carious and sound root surfaces
      were investigated under a wide range of excitation wavelengths. Human molar teeth
      with exposed root surfaces containing light- and dark-discolored root caries (n =
      3 of each) were selected. Emission spectra were recorded from carious and
      corresponding sound root surface areas from each tooth by using a fluorescence
      spectrophotometer at excitation wavelengths from 360 nm up to 580 nm, in steps of
      20 nm. The spectra were corrected for fluctuations in detector sensitivity and
      excitation light intensity, and normalized to peak intensity. Excitation spectra
      were recorded for selected emission wavelengths that showed maximum intensity.
      Light- and dark-discolored root surface caries showed distinct fluorescence
      emission bands between 600 and 700 nm that were not present in sound root surface
      areas. These bands were strongest for excitation wavelengths between 390 and 420
      nm. The excitation spectra of root caries revealed maximum excitation at around
      405 nm, which is equivalent to the Soret band of porphyrin compounds. The
      emission spectra of both types of root caries lesions were shifted towards longer
      wavelengths (red shift at half maximum) when compared to the spectra of
      corresponding sound root surfaces. The red shift for dark-discolored root caries
      was higher than for light-discolored lesions at all excitation wavelengths.

PMID- 15560832
TI  - Mechanical properties across hypomineralized/hypoplastic enamel of first
      permanent molar teeth.
AB  - The aims of the present study were to investigate the mechanical properties of
      first permanent molars affected with enamel hypomineralization or hypoplasia, and
      to describe the appearance of these lesions under scanning electron microscopy.
      Eight first permanent molar test teeth and two unaffected premolars (controls)
      were enclosed in resin, then sectioned axially and polished. The hardness and
      modulus of elasticity was determined from a single array of indentations made
      parallel to the amelo-dentinal junction using an Ultra-Micro-Indentation system.
      The teeth were then examined using the scanning electron microscope. The
      mechanical properties of the test teeth in the unaffected cervical region
      (hardness and modulus range, 2.03-4.99 GPa and 50.39-96.87 GPa, respectively)
      were similar to those of the control enamel (hardness and modulus range, 2.71
      4.15 GPa and 62.06-95.77 GPa, respectively). Between the unaffected cervical
      enamel and the hypomineralized region there was a transitional area of 500-600
      microm where the mechanical properties in the experimental teeth decreased
      linearly. The mechanical properties of the hypomineralized region of each
      experimental tooth were significantly lower than those of the control or cervical
      regions (hardness and modulus range, 0.07-1.74 GPa and 3.26-40.96 GPa,
      respectively). The scanning electron microscopy views revealed disorganized
      enamel with poorly demarcated prism boundaries in the affected regions. In
      conclusion, the hardness and modulus of elasticity of hypomineralized enamel in
      first permanent molars is significantly less than in unaffected areas of the same
      tooth. The reason for this is unclear but may be related to the lack of
      organization of the enamel crystals.

PMID- 15560833
TI  - Electron microscopic detection of salivary alpha-amylase in the pellicle formed
      in situ.
AB  - Immunological and biochemical analyses have shown that alpha-amylase is an
      essential component of the acquired pellicle. After adsorption, this enzyme might
      act as a receptor for bacterial adherence. However, data indicating that amylase
      is bound to the pellicle surface in vivo and thus available for adhering bacteria
      are rare. Therefore, the present study focused on alpha-amylase within the
      pellicle formed in situ, using gold-immunolabeling electron microscopic
      techniques. Pellicles were formed by intra-oral exposure of enamel specimens for
      30 and 120 min in six subjects. The results obtained by transmission electron
      microscopy indicate that amylase was randomly distributed in the pellicle layer
      without any preferential localization within the pellicle. Thus, salivary alpha
      amylase might be considered as an important structural component that is even
      involved in the early stages of pellicle formation. The findings of field
      emission in-lens scanning electron microscopy provided evidence that the enzyme
      is located on the pellicle surface. It could be concluded that alpha-amylase
      might act as a receptor for bacterial adherence to the pellicle in vivo.

PMID- 15560834
TI  - Ellipsometry analysis of the in vitro adsorption of tea polyphenols onto salivary
      pellicles.
AB  - The adsorption of components from black tea and of purified tea polyphenols onto
      a whole unstimulated salivary pellicle-like protein layer, formed in vitro on
      hydroxyapatite discs, was studied by in situ ellipsometry. It was found that
      components from black tea and the purified polyphenols epicatechin-3-gallate
      (ECG), epigallocatechin-3-gallate (EGCG) and theaflavin readily adsorbed onto the
      pellicle. Further investigations showed that under the experimental conditions of
      this study, no black tea- or purified polyphenol-modified pellicles were eluted
      by either phosphate buffer or sodium dodecyl sulphate rinses. Therefore, black
      tea and its polyphenol components are indicated to have a profound effect on in
      vitro pellicle modification. Similar effects were observed for tannic acid.

PMID- 15560835
TI  - Do different implant surfaces exposed in the oral cavity of humans show different
      biofilm compositions and activities?
AB  - Osseointegrated dental implants play an important role in restorative dentistry.
      However, plaque accumulation may cause inflammatory reactions around the
      implants, sometimes leading to implant failure. In this in vivo study the
      influence of two physical hard coatings on bacterial adhesion was examined in
      comparison with a pure titanium surface. Thin glass sheets coated with titanium
      nitride (TiN), zirconium nitride (ZrN) or pure titanium were mounted on removable
      intraoral splints in two adults. After 60 h of intraoral exposure, the biofilms
      were analyzed to determine the number of bacteria, the types of bacteria [by
      applying single-strand conformation polymorphism (SSCP analysis) of 16S rRNA
      genes], and whether or not the bacteria were active (by SSCP analysis of 16S
      rRNA). The results showed that bacterial cell counts were higher on the pure
      titanium-coated glass sheets than on the glass sheets coated with TiN or ZrN. The
      lowest number of bacterial cells was present on theZrN-coated glass. However, the
      metabolic activity (RNA fingerprints) of bacteria on TiN- and ZrN-coated glass
      sheets seemed to be lower than the activity of bacteria on the titanium-coated
      surfaces, whereas SSCP fingerprints based on 16S rDNA revealed that the major 16S
      bands are common to all of the fingerprints, independently of the surface
      coating.

PMID- 15560836
TI  - Single species biofilm-forming ability of root canal isolates on gutta-percha
      points.
AB  - The participation of bacterial biofilms in the over-filled gutta-percha points
      associated with refractory periapical periodontitis has recently been reported.
      This study investigated the initial biofilm-forming ability of root canal
      isolates (Enterococcus faecalis, Streptococcus sanguis, Strep. intermedius,
      Strep. pyogenes, Staphylococcus aureus, Fusobacterium nucleatum,
      Propionibacterium acnes, Porphyromonas gingivalis and Prevotella intermedia) on
      gutta-percha points in vitro. Each bacterial strain was suspended in 100% cell
      culture medium or in culture medium containing 4.5, 45 or 90% (vol/vol) serum.
      The bacterial suspensions were then co-incubated anaerobically with gutta-percha
      points for 7 d. The gutta-percha points were processed for scanning electron
      microscopic observation and examined for biofilm presence and thickness. E.
      faecalis, Strep. sanguis, Strep. intermedius, Strep. pyogenes and Staph. aureus
      biofilms were generated on the surfaces of the specimens incubated in culture
      medium supplemented with 45 or 90% (vol/vol) serum. The E. faecalis and Strep.
      sanguis biofilms were significantly thicker than those of Strep. intermedius,
      Strep. pyogenes and Staph. aureus. No biofilms were detected on the specimens
      incubated with F. nucleatum, Prop. acnes, Porph. gingivalis and Prev. intermedia.
      These findings suggest that Gram-positive facultative anaerobes have the ability
      to colonize and form extracellular matrices on gutta-percha points, while serum
      plays a crucial role in biofilm formation.

PMID- 15560837
TI  - Influence of pH and time on organic substance release from a model dental
      composite: a fluorescence spectrophotometry and gas chromatography/mass
      spectrometry analysis.
AB  - In this study we assessed the influence of pH and time on the degradation and
      elution of organic substances from the composite resin material, Z-100. To
      accomplish this, fluorescence spectrophotometry was evaluated as an appropriate
      technique for the identification of six organic substances (methacrylic acid,
      methyl methacrylate, hydroquinone, ethylene glycol dimethacrylate, triethylene
      glycol dimethacrylate and 4,4'-isopropylidenediphenol) that were eluted from
      resin composite material stored for 24 h or 6 months at pH 4.0, 6.0 or 8.0. In
      addition, complementary analyses (solid-phase microextraction/gas
      chromatography/mass spectrometry) were carried out to identify and quantify the
      substances. The main substances leached from the resin composite were methacrylic
      acid, triethylene glycol dimethacrylate and hydroquinone. It was concluded that
      fluorescence spectrophotometry seems to be a suitable, non-destructive technique
      for the qualitative analysis of eluted organic components. Critical combinations
      of time and pH allowed the elution of several organic substances, predominantly
      methacrylic acid, triethylene glycol dimethacrylate and hydroquinone, from the
      model resin composite, Z-100.

PMID- 15560838
TI  - Real-time dimensional change in light-cured composites at various depths using
      laser speckle contrast analysis.
AB  - Laser speckle contrast analysis is an interferometric technique that is used to
      measure the displacement of the rough surface of a specimen. The purpose of this
      study was to present a laser speckle correlation method for monitoring real-time
      dimensional changes of light-cured composites. Uncured composite was condensed
      into a glass tube and irradiated for 30 s with 600 or 200 mW cm(-2). The speckle
      patterns obtained from lateral and bottom composite surfaces were monitored using
      a speckle analyser. The speckle field is recorded in a digital frame and stored
      by image processing system as the carrier of information on the displacement of
      the tested surface. The calculated values were obtained for each pair of adjacent
      patterns and the changes in speckle contrast as a function time were obtained
      from five repeated measurements. The overall magnitude of the speckle contrasts
      decreased soon after the initial light exposure and gradually increased
      thereafter. The speckle contrasts obtained from the bottom surface were smaller
      than those obtained from the lateral surface. This tendency was more pronounced
      when the specimen was irradiated with lower power density. It can be concluded
      that monitoring differential shrinkage at various levels of depth can be achieved
      with this new technique.

PMID- 15560839
TI  - Molecular analyses of the candidate tumor suppressor gene, PLAGL1, in benign and
      malignant salivary gland tumors.
AB  - Deletions affecting the long arm of chromosome 6 are a characteristic feature of
      all major subtypes of malignant salivary gland tumors. Moreover, a subgroup of
      adenoid cystic carcinomas have t(6;9)(q23-25;p21-24) translocations with
      breakpoints located within the commonly deleted region. Here we have examined the
      possible involvement of the candidate tumor suppressor gene, PLAGL1, in these
      deletions and translocations. Northern blot and fluorescence in situ
      hybridization (FISH) analyses of a series of 27 salivary gland tumors revealed no
      significant changes in the gene expression or rearrangements of PLAGL1. FISH
      analysis also demonstrated that the 6q translocation breakpoint in adenoid cystic
      carcinomas with t(6;9) is proximal to the PLAGL1 locus. Collectively, these
      results indicate that PLAGL1 is not likely to be the major target gene of the 6q
      rearrangements in salivary gland tumors.

PMID- 15560840
TI  - Immunoexpression of extracellular matrix proteins in human salivary gland
      development.
AB  - Immunoexpression of the extracellular matrix (ECM) proteins laminin, fibronectin,
      tenascin and types I, III and IV collagen was analyzed in the major and minor
      salivary glands of seven human fetuses at different gestational ages. The results
      showed the presence and localization of laminin, collagen IV and fibronectin
      around glandular structures at all stages of development. Tenascin was only
      detectable around excretory ducts. In the earliest stages of development, type I
      and type III collagen were presented as fine fibers delineating the glandular
      structures and delimiting the extension of the future lobule. As glandular
      development proceeded, the lobule was gradually filled with collagens and
      glandular tissue.

PMID- 15560841
TI  - Public sector reform and demand for human resources for health (HRH).
AB  - This article considers some of the effects of health sector reform on human
      resources for health (HRH) in developing countries and countries in transition by
      examining the effect of fiscal reform and the introduction of decentralisation
      and market mechanisms to the health sector.Fiscal reform results in pressure to
      measure the staff outputs of the health sector. Financial decentralisation often
      leads to hospitals becoming "corporatised" institutions, operating with business
      principles but remaining in the public sector. The introduction of market
      mechanisms often involves the formation of an internal market within the health
      sector and market testing of different functions with the private sector. This
      has immediate implications for the employment of health workers in the public
      sector, because the public sector may reduce its workforce if services are
      purchased from other sectors or may introduce more short-term and temporary
      employment contracts.Decentralisation of budgets and administrative functions can
      affect the health sector, often in negative ways, by reducing resources available
      and confusing lines of accountability for health workers. Governance and
      regulation of health care, when delivered by both public and private providers,
      require new systems of regulation.The increase in private sector provision has
      led health workers to move to the private sector. For those remaining in the
      public sector, there are often worsening working conditions, a lack of employment
      security and dismantling of collective bargaining agreements.Human resource
      development is gradually being recognised as crucial to future reforms and the
      formulation of health policy. New information systems at local and regional level
      will be needed to collect data on human resources. New employment arrangements,
      strengthening organisational culture, training and continuing education will also
      be needed.

PMID- 15560842
TI  - Hysterectomy at a Canadian tertiary care facility: results of a one year
      retrospective review.
AB  - BACKGROUND: The purpose of this study was to investigate the indications for and
      approach to hysterectomy at Kingston General Hospital (KGH), a teaching hospital
      affiliated with Queen's University at Kingston, Ontario. In particular, in light
      of current literature and government standards suggesting the superiority of
      vaginal versus abdominal approaches and a high number of concurrent
      oophorectomies, the aim was to examine the circumstances in which concurrent
      oophorectomies were performed and to compare abdominal and vaginal hysterectomy
      outcomes. METHODS: A retrospective chart audit of 372 consecutive hysterectomies
      performed in 2001 was completed. Data regarding patient characteristics, process
      of care and outcomes were collected. Data were analyzed using descriptive
      statistics, t-tests and linear and logistic regression. RESULTS: Average age was
      48.5 years, mean body mass index (BMI) was 28.6, the mean length of stay (LOS)
      was 5.2 days using an abdominal approach and 3.0 days using a vaginal approach
      without laparoscopy. 14% of hysterectomies were performed vaginally, 5.9% were
      laparoscopically assisted vaginal hysterectomies and the rest were abdominal
      hysterectomies. The most common indication was dysfunctional or abnormal uterine
      bleeding (37%). The average age of those that had an oophorectomy (removal of
      both ovaries) was 50.8 years versus 44.3 years for those that did not (p < .05).
      Factors associated with LOS included surgical approach, age and the number of
      concurrent procedures. CONCLUSIONS: A significant reduction in LOS was found
      using the vaginal approach. Both the patient and the health care system may
      benefit from the tendency towards an increased use of vaginal hysterectomies. The
      audit process demonstrated the usefulness of an on-going review mechanism to
      examine trends associated with common surgical procedures.

PMID- 15560843
TI  - Cost-effectiveness of an intensive group training protocol compared to
      physiotherapy guideline care for sub-acute and chronic low back pain: design of a
      randomised controlled trial with an economic evaluation. [ISRCTN45641649].
AB  - BACKGROUND: Low back pain is a common disorder in western industrialised
      countries and the type of treatments for low back pain vary considerably.
      METHODS: In a randomised controlled trial the cost-effectiveness and cost-utility
      of an intensive group training protocol versus physiotherapy guideline care for
      sub-acute and chronic low back pain patients is evaluated. Patients with back
      pain for longer than 6 weeks who are referred to physiotherapy care by their
      general practitioner or medical specialist are included in the study. The
      intensive group training protocol combines exercise therapy with principles of
      behavioural therapy ("graded activity") and back school. This training protocol
      is compared to physiotherapy care according to the recently published Low Back
      Pain Guidelines of the Royal Dutch College for Physiotherapy. Primary outcome
      measures are general improvement, pain intensity, functional status, work
      absenteeism and quality of life. The direct and indirect costs will be assessed
      using cost diaries. Patients will complete questionnaires at baseline and 6, 13,
      26 and 52 weeks after randomisation. DISCUSSION: No trials are yet available that
      have evaluated the effect of an intensive group training protocol including
      behavioural principles and back school in a primary physiotherapy care setting
      and no data on cost-effectiveness and cost-utility are available.

PMID- 15560844
TI  - The in vitro effect of gefitinib ('Iressa') alone and in combination with
      cytotoxic chemotherapy on human solid tumours.
AB  - BACKGROUND: Activation of the epidermal growth factor receptor (EGFR) triggers
      downstream signaling pathways that regulate many cellular processes involved in
      tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine
      kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1).
      METHODS: In this study we have used a standardised ATP-based tumour
      chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in
      combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin
      and treosulfan) against a variety of solid tumours (n = 86), including breast,
      colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site,
      cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma. The
      IC50 and IC90 were calculated for each single agent or combination. To allow
      comparison between samples the IndexSUM was calculated based on the percentage
      tumour growth inhibition (TGI) at each test drug concentration (TDC). Gefitinib
      was tested at concentrations ranging from 0.0625-2 microM (TDC = 0.446
      microg/ml). This study represents the first use of a TKI in the assay. RESULTS:
      There was heterogeneity in the degree of TGI observed when tumours were tested
      against single agent gefitinib. 7% (6/86) of tumours exhibited considerable
      inhibition, but most showed a more modest response resulting in a low TGI. The
      median IC50 value for single agent gefitinib in all tumours tested was 3.98
      microM. Interestingly, gefitinib had both positive and negative effects when used
      in combination with different cytotoxics. In 59% (45/76) of tumours tested, the
      addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or
      combination (of these, 11% (5/45) had a >50% decrease in their IndexSUM). In 38%
      of tumours (29/76), the TGI was decreased when the combination of gefitinib +
      cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3%
      (2/76) there was no change observed. CONCLUSION: The in vitro model suggests that
      gefitinib may have differential effects in response to concomitant cytotoxic
      chemotherapy with the agents tested during this study. The mechanism involved may
      relate to the effect of TKIs on growth rate versus their effect on the ability of
      the cell to survive the stimulus to apoptosis produced by chemotherapy.

PMID- 15560845
TI  - Human T lymphotropic virus type-1 p30II alters cellular gene expression to
      selectively enhance signaling pathways that activate T lymphocytes.
AB  - BACKGROUND: Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that
      causes adult T-cell leukemia/lymphoma and is implicated in a variety of
      lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory
      genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and
      p30II, which are incompletely defined in the virus life cycle or HTLV-1
      pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the
      ability of the virus to maintain viral loads in vivo. Exogenous expression of
      p30II differentially modulates CREB and Tax-responsive element-mediated
      transcription through its interaction with CREB-binding protein/p300 and
      represses tax/rex RNA nuclear export. RESULTS: Herein, we further characterized
      the role of p30II in regulation of cellular gene expression, using stable p30II
      expression system employing lentiviral vectors to test cellular gene expression
      with Affymetrix U133A arrays, representing approximately 33,000 human genes.
      Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T
      lymphocytes were used to confirm selected gene expression patterns. Our data
      reveals alterations of interrelated pathways of cell proliferation, T-cell
      signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all
      categories, p30II appeared to be an overall repressor of cellular gene
      expression, while selectively increasing the expression of certain key regulatory
      genes. CONCLUSIONS: We are the first to demonstrate that p30II, while repressing
      the expression of many genes, selectively activates key gene pathways involved in
      T-cell signaling/activation. Collectively, our data suggests that this complex
      retrovirus, associated with lymphoproliferative diseases, relies upon accessory
      gene products to modify cellular environment to promote clonal expansion of the
      virus genome and thus maintain proviral loads in vivo.

PMID- 15560846
TI  - Biochemical prevention and treatment of viral infections - a new paradigm in
      medicine for infectious diseases.
AB  - For two centuries, vaccination has been the dominating approach to develop
      prophylaxis against viral infections through immunological prevention. However,
      vaccines are not always possible to make, are ineffective for many viral
      infections, and also carry certain risk for a small, yet significant portion of
      the population. In the recent years, FDA's approval and subsequent market
      acceptance of Synagis, a monoclonal antibody indicated for prevention and
      treatment of respiratory syncytial virus (RSV) has heralded a new era for viral
      infection prevention and treatment. This emerging paradigm, herein designated
      "Biochemical Prevention and Treatment", currently involves two aspects: (1)
      preventing viral entry via passive transfer of specific protein-based anti-viral
      molecules or host cell receptor blockers; (2) inhibiting viral amplification by
      targeting the viral mRNA with anti-sense DNA, ribozyme, or RNA interference
      (RNAi). This article summarizes the current status of this field.

PMID- 15560847
TI  - Prevention of genital herpes in a guinea pig model using a glycoprotein D
      specific single chain antibody as a microbicide.
AB  - BACKGROUND: Genital herpes (GH) is a recurrent sexually transmitted infection
      (STI) that causes significant morbidity and is also the major source of herpes
      simplex virus (HSV) in cases of neonatal herpes. Vaccination is a current goal
      which has had limited success so far in preventing GH and microbicides offer an
      attractive alternative. Treatment of primary disease cannot prevent establishment
      of latent infections and thus, cannot prevent subsequent recurrent disease.
      Recently, many of the molecular events leading to entry of HSV into cells have
      been elucidated, resulting in the description of a number of herpesvirus entry
      mediators (HVEMs) that interact with HSV glycoprotein D (gD) on the surface of
      virions. Described here is a strategy for interrupting the spread of HSV based on
      interfering with these interactions. The hypothesis addressed in the current
      report was that single chain antibody variable fragments (scFv) that interrupt
      associations between gD and HVEMs would not only prevent infection in vitro but
      could also be used as microbicides to interfere with acquisition GH. RESULTS AND
      CONCLUSIONS: Here we show that a scFv derived from a particular hybridoma, DL11,
      not only inhibits infection in vitro but also prevents development of GH in a
      guinea pig model when applied intravaginally in an inert vehicle. Comparison of
      different anti-gD single chain antibodies supported the hypothesis that the
      activity of DL11-scFv is based on its ability to disrupt the associations between
      gD and the two major receptors for HSV, nectin-1 and HveA. Further, the results
      predict that bacterial expression of active single chain antibodies can be
      optimized to manufacture inexpensively a useful microbicidal product active
      against HSV.

PMID- 15560848
TI  - 4-D single particle tracking of synthetic and proteinaceous microspheres reveals
      preferential movement of nuclear particles along chromatin - poor tracks.
AB  - BACKGROUND: The dynamics of nuclear organization, nuclear bodies and RNPs in
      particular has been the focus of many studies. To understand their function,
      knowledge of their spatial nuclear position and temporal translocation is
      essential. Typically, such studies generate a wealth of data that require novel
      methods in image analysis and computational tools to quantitatively track
      particle movement on the background of moving cells and shape changing nuclei.
      RESULTS: We developed a novel 4-D image processing platform (TIKAL) for the work
      with laser scanning and wide field microscopes. TIKAL provides a registration
      software for correcting global movements and local deformations of cells as well
      as 2-D and 3-D tracking software. With this new tool, we studied the dynamics of
      two different types of nuclear particles, namely nuclear bodies made from GFP-NLS
      vimentin and microinjected 0.1 mum - wide polystyrene beads, by live cell time
      lapse microscopy combined with single particle tracking and mobility analysis. We
      now provide a tool for the automatic 3-D analysis of particle movement in
      parallel with the acquisition of chromatin density data. CONCLUSIONS: Kinetic
      analysis revealed 4 modes of movement: confined obstructed, normal diffusion and
      directed motion. Particle tracking on the background of stained chromatin
      revealed that particle movement is directly related to local reorganization of
      chromatin. Further a direct comparison of particle movement in the nucleoplasm
      and the cytoplasm exhibited an entirely different kinetic behaviour of vimentin
      particles in both compartments. The kinetics of nuclear particles were slightly
      affected by depletion of ATP and significantly disturbed by disruption of actin
      and microtubule networks. Moreover, the hydration state of the nucleus had a
      strong impact on the mobility of nuclear bodies since both normal diffusion and
      directed motion were entirely abolished when cells were challenged with 0.6 M
      sorbitol. This effect correlated with the compaction of chromatin. We conclude
      that alteration in chromatin density directly influences the mobility of protein
      assemblies within the nucleus.

PMID- 15560849
TI  - SMAC is expressed de novo in a subset of cervical cancer tumors.
AB  - BACKGROUND: Smac/Diablo is a recently identified protein that is released from
      mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation
      and cell death. In view of its activity it might participate in carcinogenesis.
      In the present study, we analyzed Smac expression in a panel of cervical cancer
      patients. METHODS: We performed semi quantitative RT-PCR on 41 cervical tumor and
      6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17
      stage III; and a control group of 6 samples of normal cervical squamous
      epithelial tissue. RESULTS: Smac mRNA expression was below the detection limit in
      the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical
      cancer biopsies showed detectable levels of this transcript. The samples
      expressing Smac were distributed equally among the stages (5 in stage I, 4 in
      stage II and 4 in stage III) with similar expression levels. We found no
      correlation between the presence of Smac mRNA and histology, menopause, WHO stage
      or disease status. CONCLUSIONS: Smac is expressed de novo in a subset of cervical
      cancer patients, reflecting a possible heterogeneity in the pathways leading to
      cervical cancer. There was no correlation with any clinical variable.

PMID- 15560850
TI  - BAG-1 haplo-insufficiency impairs lung tumorigenesis.
AB  - BACKGROUND: BAG-1 is a multifunctional co-chaperone of heat shock proteins
      (Hsc70/Hsp70) that is expressed in most cells. It interacts with Bcl-2 and Raf
      indicating that it might connect protein folding with other signaling pathways.
      Evidence that BAG-1 expression is frequently altered in human cancers, in
      particular in breast cancer, relative to normal cells has been put forward but
      the notion that overexpression of BAG-1 contributes to poor prognosis in
      tumorigenesis remains controversial. METHODS: We have evaluated the effect of BAG
      1 heterozygosity in mice in a model of non-small-cell lung tumorigenesis with
      histological and molecular methods. We have generated mice heterozygous for BAG
      1, carrying a BAG-1 null allele, that in addition express oncogenic,
      constitutively active C-Raf kinase (SP-C C-Raf BxB) in type II pneumocytes. SP-C
      C-Raf BxB mice develop multifocal adenomas early in adulthood. RESULTS: We show
      that BAG-1 heterozygosity in mice impairs C-Raf oncogene-induced lung adenoma
      growth. Lung tumor initiation was reduced by half in BAG-1 heterozygous SP-C C
      Raf BxB mice compared to their littermates. Tumor area was reduced by 75% in 4
      month lungs of BAG-1 haploinsufficient mice compared to mice with two BAG-1
      copies. Whereas BAG-1 heterozygosity did not affect the rate of cell
      proliferation or signaling through the mitogenic cascade in adenoma cells, it
      increased the rate of apoptosis. CONCLUSION: Reduced BAG-1 expression
      specifically targets tumor cells to apoptosis and impairs tumorigenesis. Our data
      implicate BAG-1 as a key player in oncogenic transformation by Raf and identify
      it as a potential molecular target for cancer treatment.

PMID- 15560858
TI  - Theory of obstetrics: the fetuses-at-risk approach as a causal paradigm.

PMID- 15560851
TI  - cDNA microarray analysis of bovine embryo gene expression profiles during the pre
      implantation period.
AB  - BACKGROUND: After fertilization, embryo development involves differentiation, as
      well as development of the fetal body and extra-embryonic tissues until the
      moment of implantation. During this period various cellular and molecular changes
      take place with a genetic origin, e.g. the elongation of embryonic tissues, cell
      cell contact between the mother and the embryo and placentation. To identify
      genetic profiles and search for new candidate molecules involved during this
      period, embryonic gene expression was analyzed with a custom designed utero
      placental complementary DNA (cDNA) microarray. METHODS: Bovine embryos on days 7,
      14 and 21, extra-embryonic membranes on day 28 and fetuses on days 28 were
      collected to represent early embryo, elongating embryo, pre-implantation embryo,
      post-implantation extra-embryonic membrane and fetus, respectively. Gene
      expression at these different time points was analyzed using our cDNA microarray.
      Two clustering algorithms such as k-means and hierarchical clustering methods
      identified the expression patterns of differentially expressed genes across pre
      implantation period. Novel candidate genes were confirmed by real-time RT-PCR.
      RESULTS: In total, 1,773 individual genes were analyzed by complete k-means
      clustering. Comparison of day 7 and day 14 revealed most genes increased during
      this period, and a small number of genes exhibiting altered expression decreased
      as gestation progressed. Clustering analysis demonstrated that trophoblast-cell
      specific molecules such as placental lactogens (PLs), prolactin-related proteins
      (PRPs), interferon-tau, and adhesion molecules apparently all play pivotal roles
      in the preparation needed for implantation, since their expression was remarkably
      enhanced during the pre-implantation period. The hierarchical clustering analysis
      and RT-PCR data revealed new functional roles for certain known genes (dickkopf
      1, NPM, etc) as well as novel candidate genes (AW464053, AW465434, AW462349,
      AW485575) related to already established trophoblast-specific genes such as PLs
      and PRPs. CONCLUSIONS: A large number of genes in extra-embryonic membrane
      increased up to implantation and these profiles provide information fundamental
      to an understanding of extra-embryonic membrane differentiation and development.
      Genes in significant expression suggest novel molecules in trophoblast
      differentiation.

PMID- 15560859
TI  - Attitudes of women who are currently using or recently stopped estrogen
      replacement therapy with or without progestins: results of the AWARE survey.
AB  - OBJECTIVE: To examine the level of awareness of the findings of the Women's
      Health Initiative (WHI) study among recent users of hormone therapy (HT).
      METHODS: A survey was conducted on Canadian women older than 45 years of age who
      had used either an oral, topical, or vaginal HT within the preceding 3 years.
      Questionnaires were mailed to a random sample of 210 eligible women within an
      academic subspecialty rheumatology/osteoporosis practice between April and June
      2003. Questionnaires were also provided upon request to women attending tertiary
      care multidisciplinary clinics and 6 community pharmacies in Hamilton, Ontario.
      The 98 questions in the survey were either categorical in nature (yes or no
      response) or followed by a Likert scale. Using chi-square and Student t tests,
      the responses of women who used combination estrogen/progestin were compared to
      those who used estrogen alone. RESULTS: Of the 161 women who responded to the
      survey (128 from the osteoporosis practice, 33 from other clinics and
      pharmacies), 102 (63%) had used HT for more than 5 years. Ninety-one of 159
      respondents (57%) discontinued HT, and 63% (57/91) of those stopped using HT
      after publication of the WHI principal findings. Sixty-four percent (33/52) of
      women on combination estrogen/progestin discontinued HT, compared to 50% (46/93)
      who were on estrogen only, and 5 other women who also discontinued HT but did not
      know what type of preparation they had been taking (P = .04 for the difference in
      rates between the 3 groups). Knowledge of the findings of the estrogen/progestin
      arm of the WHI study did not significantly differ among users of different types
      of hormone preparations. Of the women who indicated that they did not know if HT
      affected the risk of WHI-studied medical conditions, 44% (69/156) indicated being
      unaware of HT risks for stroke, 28% (44/157) for hip fracture, 39% (60/155) for
      myocardial infarction, 25% (39/155) for breast cancer, and 48% (73/152) for blood
      clots. Women who had recently taken HT generally did not regret their use of HT.
      CONCLUSION: Although many women discontinued HT following the publication of the
      principal findings of the estrogen/progestin arm of the WHI study, the majority
      of these women lacked a clear understanding of those findings.

PMID- 15560860
TI  - Determinants of breast-feeding and weaning in Alberta, Canada.
AB  - OBJECTIVE: To assess the determinants of breast-feeding initiation and duration
      at the population level in Alberta, Canada. METHODS: Determinants of breast
      feeding were assessed based on data from a sample of 1113 women, who represented
      150,898 fertile women in Alberta, in the second cycle of the National Population
      Health Survey conducted 1996-97. Logistic regression analysis was used to
      estimate the independent effects of various determinants of breast-feeding
      initiation and duration dichotomized at 4 weeks, 8 weeks, 12 weeks, and 6 months
      postpartum. All analyses used analytic weights to take both the average design
      effect and population weights for the complex survey design into account.
      RESULTS: The proportion of breast-feeding initiation was 85.6%. It was observed
      that 71.3% of mothers continued breast-feeding for at least 3 months, and 37.2%
      of mothers breast-fed their infants for more than 6 months. Determinants of
      breast-feeding initiation were marital status, education, maternal smoking
      behaviour, and annual family income. White women and women who were older than 35
      years of age were more likely to continue breast-feeding for longer periods,
      whereas those who smoked during pregnancy were less likely to breast-feed their
      infants for extended periods. The primary reasons for weaning were breast
      problems at less than 1 week, insufficient milk production during weeks 1 to 12,
      and infants who weaned themselves after 3 months. CONCLUSIONS: Smoking cessation
      during pregnancy, adequate treatment of early breast problems, and breast-feeding
      promotion campaigns targeting socioeconomically disadvantaged populations could
      serve to increase breast-feeding in Canada.

PMID- 15560861
TI  - The role of thyroid hormone in trophoblast function, early pregnancy maintenance,
      and fetal neurodevelopment.
AB  - OBJECTIVE: To review the literature on the roles of thyroid hormone in
      trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.
      METHODS: MEDLINE was searched for English-language papers published from 1971 to
      2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy,"
      "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid
      hormone replacement therapy," "thyroid hormone-responsive gene," and
      "trophoblast." RESULTS: Transplacental transfer of thyroid hormone occurs before
      the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and
      iodothyronine deiodinases are present in the placenta and the fetal central
      nervous system early in pregnancy, and thyroid hormone plays a crucial role both
      in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is
      associated with a high rate of spontaneous abortion and long-term
      neuropsychological deficits in children born of hypothyroid mothers. Maternal
      iodine deficiency also causes a wide spectrum of neuropsychological disorders in
      children, ranging from subclinical deficits in cognitive motor and auditory
      functions to hypothyroid-induced cognitive impairment in infants. However, these
      conditions are preventable when iodine supplementation is initiated before the
      second trimester. Although thyroid hormone replacement therapy is effective for
      reducing the adverse effects complicated by maternal hypothyroidism, the
      appropriate dose of thyroid hormone is mandatory in protecting the early stage of
      pregnancy. CONCLUSIONS: Close monitoring of maternal thyroid hormone status and
      ensuring adequate maternal thyroid hormone levels in early pregnancy are of great
      importance to prevent miscarriage and neuropsychological deficits in infants.

PMID- 15560862
TI  - Legal dimensions of adolescent sexuality.
AB  - The ethical and legal obligations with respect to treating a minor can be
      confusing, particularly in the areas of consent to treatment, confidentiality,
      and parental involvement. The clinician must be aware of the appropriate course
      of practice when the patient is an adolescent seeking care for contraception,
      pregnancy, or sexually transmitted infections. This article examines a number of
      ethical and legal issues that arise when providing reproductive and sexual health
      care to an adolescent and offers recommendations for the physician's most
      appropriate courses of action regarding adolescent patients and the age of
      consent to sexual activity, reporting of child abuse, provision of reproductive
      and sexual health care to a minor, assessing an adolescent's capacity to consent
      to treatment, the physician's duty of confidentiality, and the exceptions to the
      rule of confidentiality.

PMID- 15560863
TI  - Methotrexate embryopathy in a surviving intrauterine fetus after presumed
      diagnosis of ectopic pregnancy: case report.
AB  - CASE: A 30-year-old woman with a history of 6 spontaneous first trimester
      abortions and no living children, who had previously been treated for polycystic
      ovarian syndrome, was given methotrexate parenterally for a suspected ectopic
      pregnancy at 5 weeks of amenorrhea. Later, a surviving intrauterine pregnancy was
      noted, and the pregnancy continued. Her baby was delivered with multiple skeletal
      anomalies and ambiguous genitalia. CONCLUSION: Physicians must discuss the
      teratogenicity of methotrexate with their patients before its administration.
      Careful clinical and ultrasound evaluations are recommended before the
      administration of methotrexate to avoid complications in pregnancy and adverse
      birth outcomes.

PMID- 15560864
TI  - Report of the 2003 pan-Canadian forum on cervical cancer prevention and control.
AB  - OBJECTIVE: To develop evidence-based consensus recommendations on the delivery of
      cervical cancer screening, human papillomavirus (HPV) education, HPV testing, and
      the optimal tool for cervical cytology within the Canadian health system.
      PARTICIPANTS: Leading up to a forum held in Ottawa on November 21 and 22, 2003,
      254 registrants reviewed position papers through a Web-based discussion group.
      Experts in program management, clinical practice, epidemiology, public health,
      economics, and women's health, representing 48 organizations, then participated
      in the 2-day forum to develop consensus recommendations. EVIDENCE: Writing groups
      prepared position papers on optimal methods for cervical cytology; education
      concerning HPV; HPV testing in primary screening; HPV testing as a triage tool in
      cytopathology; and delivery mechanisms for cervical screening. Systematic reviews
      were the primary source of evidence supplemented by literature searches.
      CONSENSUS PROCESS: Feedback from Web-based discussions was incorporated into
      consecutive drafts of position papers. At the forum, recommendations and
      supporting evidence were presented, further debated in small-group sessions, and
      discussed in a plenary session. Despite divergent professional mandates and
      opinions, consensus was achieved on 15 recommendations across all areas. Final
      recommendations were posted to the Web for further input and circulated for
      written consensus by participants. CONCLUSIONS: The recommendations cover the use
      of new evidence and technologies in cervical cancer prevention in Canada and
      provide a framework for provision of HPV education, planning the implementation
      of new cervical screening technologies in Canada, the development of evaluation
      plans, and new research areas.

PMID- 15560865
TI  - Evolution of GnRH ligand precursors and GnRH receptors in protochordate and
      vertebrate species.
AB  - Primary structure relationships between GnRH precursors or GnRH receptors have
      received significant attention recently due to rapid DNA sequence determination
      of gene fragments and cDNAs from diverse species. Concepts concerning the
      evolutionary history of the GnRH system and its function in mammals, including
      humans, are likely to be modified as more complete sequence information becomes
      available. Current evidence suggests occurrence of fewer GnRH ligand and GnRH
      receptor genes in mammals compared to protochordates, fish and amphibians. Whilst
      several sequence-related GnRH decapeptide precursors and 2 or 3 separate GnRH
      receptors are encoded within the genomes of protochordates, fish and amphibians,
      only two types of GnRH (GnRH-I and GnRH-II) and two GnRH receptors occur in
      mammals. In addition, fish and mammalian genomes both retain inactive remnants of
      GnRH ligand or GnRH receptor genes. The number of distinct GnRH receptor genes in
      teleosts (at least five complete genes in pufferfish and three in zebrafish)
      partly reflects whole genome duplication during the evolution of this order of
      animals. Three GnRH receptor genes occur in certain frog species, consistent with
      the occurrence of up to three types of prepro-GnRH in amphibians. In contrast,
      only one functional GnRH receptor gene (the type I GnRH receptor) has been
      identified in humans and chimpanzees and a gene encoding a second receptor,
      homologous to a functional monkey receptor (the type II GnRH receptor), is either
      partially or completely silenced in a range of mammalian species (human,
      chimpanzee, sheep, cow, rat, and mouse). Further work is required to determine
      the significance of species-specific differences in the GnRH system to
      reproductive biology. For instance, recent data show that even species as closely
      related as humans and chimpanzees exhibit important organisational changes in the
      genes comprising the GnRH system.

PMID- 15560866
TI  - Seasonal cyclicity of secretogranin-II expression and its modulation by sex
      steroids and GnRH in the female goldfish pituitary.
AB  - The secretory vesicle protein secretogranin-II (SgII), a precursor for the
      bioactive peptide secretoneurin, is expressed at all levels of the goldfish
      reproductive axis, including the hypothalamus, pituitary and ovaries. These
      findings led us to hypothesize that SgII is involved in reproduction and is
      physiologically regulated. We investigated the effects of different sex steroids
      on pituitary SgII expression throughout the seasonal reproductive cycle of the
      female goldfish, as well as the effects of GnRH and testosterone on pituitary
      LHbeta subunit, GH, and SgII expression in sexually recrudescent female fish
      using northern blot analysis. We demonstrated that SgII expression levels vary
      seasonally, with levels being highest in winter and lowest in spring. Sex
      steroids did not alter SgII expression at any of the time periods studied. In
      sexually mature goldfish, injection of a GnRH agonist stimulated the expression
      of LHbeta and SgII specifically in the pars distalis but not the
      neurointermediate lobe of the pituitary. Although testosterone alone did not
      alter the expression of either of these genes, it did abolish the stimulatory
      effects of GnRH on both LHbeta and SgII expression. This represents the first
      study where testosterone is shown to modulate SgII expression in the pituitary.

PMID- 15560867
TI  - The pancreas of the naked mole-rat (Heterocephalus glaber): an ultrastructural
      and immunocytochemical study of the endocrine component of thermoneutral and cold
      acclimated animals.
AB  - Endocrine cell distribution within the islets of Langerhans may vary both between
      species and under different energetically demanding conditions such as cold
      acclimation. The naked mole-rat, Heterocephalus glaber, lacking an effective
      insulatory pelage, is effectively a poikilotherm, yet it shows a typical
      mammalian cold-acclimation response by substantially increasing food intake to
      meet higher energy requirements when housed at lower temperatures. The endocrine
      component of the pancreas of thermoneutral and cold-acclimated naked mole-rats
      was thus characterized using immunocytochemistry and ultrastructural analyses.
      Four distinct endocrine cells were identified: alpha (glucagon-producing), beta
      (insulin-producing), delta (somatostatin-producing), and PP (pancreatic
      polypeptide-producing) cells. Distribution of these cells differed from that of
      other rodents, in that beta cells formed the mantle while alpha cells formed the
      core of the islets. This distribution may contribute to the observed insulin
      insensitivity of this species, as indicated in abnormal responses to glucose
      tolerance tests. Insulin-producing cells, however, were more numerous than
      glucagon-producing cells. This ratio was unchanged with cold acclimation.
      Immunoreactivity of alpha and beta cells was more intense in cold-acclimated than
      in thermoneutral animals, possibly indicative of a change in hormonal production
      in animals housed at a lower temperature.

PMID- 15560868
TI  - Dietary supplementation with arachidonic acid in tilapia (Oreochromis
      mossambicus) reveals physiological effects not mediated by prostaglandins.
AB  - This study aims to clarify the role of the polyunsaturated fatty acid arachidonic
      acid (ArA, 20:4n-6) in the stress response of Mozambique tilapia (Oreochromis
      mossambicus). ArA is converted into eicosanoids, including prostaglandins, which
      can influence the response to stressors. Tilapia, a species able to form ArA from
      its precursor, was supplemented with ArA for 18 days, after which they were
      confined for 5 min. Acetylsalicylic acid (ASA, COX-inhibitor) was subsequently
      administered to distinguish ArA-mediated effects from enhanced prostaglandin E(2)
      (PGE(2)) synthesis. ArA supplemented fish had higher ArA levels in gills and
      kidneys, and these levels were further enhanced after ASA treatment. Levels of
      total monounsaturated and polyunsaturated fatty acids as well as docosahexaenoic
      acid (DHA), eicosapentaenoic acid (EPA), and ArA, were altered 24h after
      confinement, particularly in the kidneys. ArA supplementation had no effect on
      basal cortisol levels, while ArA + ASA reduced basal cortisol levels. ArA + ASA
      augmented the cortisol response to confinement. The combination of ArA + ASA also
      elevated plasma basal prolactin (tPRL)(177) and 3,5,3'-triiodothyronine (T(3))
      levels. Neither ArA nor ASA affected the stress-associated increases in plasma
      glucose and lactate. Na(+), K(+)-ATPase activity in the gills was reduced after
      ArA supplementation and was even further suppressed by subsequent ASA treatment.
      In an additional feeding trial, ArA supplementation enhanced the renal Na(+),
      K(+)-ATPase activity. In vitro, ArA was a potent inhibitor of the Na(+), K(+)
      ATPase activity of gill and kidney homogenates. In contrast, PGE(2) had no effect
      on branchial ATPase, whereas the effect on renal ATPase activity was
      concentration dependent. Modifying the dietary intake of ArA alters the response
      of tilapia to an acute stressor and influences osmoregulatory processes and it is
      unlikely that these effects are due to an enhanced production of prostaglandins.

PMID- 15560869
TI  - Atrial natriuretic factor: localization in the adrenal gland of the lizard
      Podarcis sicula and effects on pituitary-adrenal axis activity.
AB  - The occurrence of atrial natriuretic factor (ANF) immunoreactivity was
      investigated in the adrenal gland of the lizard Podarcis sicula by avidin
      biotinylated peroxidase complex (ABC) immunocytochemical technique: ANF
      immunoreactivity was present in the chromaffin tissue, and was absent in the
      steroidogenic tissue. The role of ANF in the modulation of the pituitary-adrenal
      axis activity was investigated in vivo by intraperitoneal administration of ANF.
      The effects were evaluated by examination of the morphological and morphometrical
      features of the tissues, as well as the plasma levels of adrenocorticotropic
      hormone (ACTH), corticosterone, aldosterone, norepinephrine, and epinephrine. ANF
      (28 microg/100 g body wt) did not affect ACTH plasma levels, that remained almost
      unchanged; in contrast, corticosterone plasma levels increased from 6.45 +/-
      0.070 ng/ml in carrier-injected lizards to 9.69 +/- 0.080 ng/ml 24 h after the
      injection; aldosterone levels decreased from 2.19 +/- 0.010 ng/ml in carrier
      injected specimens to 0.58 +/- 0.003 ng/ml 24 h after the experimental treatment.
      In the chromaffin tissue, an increase in the number of epinephrine cells and a
      decrease in the number of norepinephrine cells were observed, decreasing the
      numeric norepinephrine/epinephrine cell ratio, from 1.4/1 of control specimens to
      0.3/1 24 h after ANF administration. Moreover, norepinephrine plasma levels
      decreased from 998 +/- 4.600 pg/ml in carrier-injected specimens to 321 +/- 2.230
      pg/ml 24 h after ANF administration; epinephrine plasma levels were elevated from
      614 +/- 3.410 pg/ml in carrier-injected specimens to 1672 +/- 10.800 pg/ml 24 h
      after the experimental treatment. The presence of ANF in the adrenal gland
      suggests that, also in reptiles as in other vertebrates, this peptide, locally
      released from the chromaffin cells, may modulate the activity of the adrenal
      gland, probably in a paracrine manner. The effects of ANF on the adrenal gland
      suggest that this peptide may affect reptilian salt and fluid homeostasis.

PMID- 15560870
TI  - Somatostatin receptor subtype 1 and subtype 2 mRNA expression is regulated by
      nutritional state in rainbow trout (Oncorhynchus mykiss).
AB  - Somatostatin receptors (sst) mediate the numerous physiological actions (e.g.,
      aspects of growth, development, and metabolism) of the somatostatin family of
      peptides. In this study, we used rainbow trout (Oncorhynchus mykiss) to establish
      the pattern of sst subtype 1A, 1B, and 2 mRNA expression in selected tissues
      (optic tectum of brain, endocrine pancreas, and liver) and to evaluate
      nutritional regulation of sst expression. Quantitative real-time reverse
      transcription-PCR, sensitive to less than 100 copies, revealed that sst1s and
      sst2 was differentially expressed, both in terms of distribution among the
      tissues of study and in terms of relative abundance within a particular tissue.
      Under normal physiological (fed) conditions, sst1B levels were two times greater
      than those of sst1A in all tissues examined and levels of sst2 were 2-5 times
      greater those of sst1B, except in optic tectum, in which sst1B and sst2 mRNA
      levels appeared equal. Nutritional state modulated the pattern of sst1 and sst2
      mRNAs expression. Fasting for 2 or 6 weeks reduced the expression of sst mRNAs in
      optic tectum; whereas, fasting increased the expression of sst mRNAs in both
      pancreas and liver. Re-feeding animals for 2 weeks following a 4-week fast
      restored mRNA levels to near those in tissues from animals which were fed
      continuously. These findings indicate that the pattern of sst expression in optic
      tectum, pancreas, and liver is regulated by nutritional state.

PMID- 15560871
TI  - Leptin increases T-cell immune response in birds.
AB  - Leptin is a 16 kDa protein hormone that besides being a satiety factor also
      functions as a pleiotropic molecule regulating endocrine and immune functions.
      The aim of this study was to investigate the role of leptin on mitogen stimulated
      T-lymphocyte proliferation in birds. In the first experiment (in vitro),
      peripheral blood was collected from turkeys and lymphocytes were isolated from
      samples. Recombinant chicken leptin was added at concentrations of 0, 10(-9), 10(
      8), 10(-7), and 10(-6) M prior to mitogen stimulation with Concavalin A. BrdU
      incorporation allowed us to detect T-cell proliferation using intracellular
      labeling of nucleic acids. Mitogen activation induced with Concavalin A caused a
      proliferation of T-cells that was positively correlated with the concentration of
      leptin. In the second experiment (in vivo), asian blue quail were fitted with
      osmotic pumps releasing leptin and injected with phytohemagglutinin (PHA) in
      their wing-webs before, during, and after leptin administration. The response to
      mitogen was greater in leptin treated birds during the leptin administration, but
      not before or after. These findings demonstrate that leptin enhances mitogen
      stimulated T-cell proliferation in birds. The results correspond with previous
      reports on mammals.

PMID- 15560872
TI  - Ontogeny of corticotropin-releasing factor and of hypothalamic-pituitary
      interrenal axis responsiveness to stress in tilapia (Oreochromis mossambicus;
      Teleostei).
AB  - The ontogeny of the corticotropin-releasing factor (CRF) system and of the
      ability of the hypothalamic-pituitary-interrenal (HPI) axis to respond to
      stressors (capture or confinement), or to cortisol treatment was investigated in
      tilapia (Oreochromis mossambicus). In 2 days post hatching (dph) larvae, the
      first developmental stage used for immunohistochemistry, CRF-immunoreactivity
      (ir) was observed in the nucleus preopticus (npo), and in two hypothalamic nuclei
      (nlt and nrl). In this stage, CRF- and AVT-ir was found in the neural part of the
      pituitary, and endocrine cells in the pars distalis and pars intermedia contained
      POMC-derived peptides. In the ventral telencephalon, CRF-ir cells were first
      observed 5 dph, whereas projections from these cells into the anterior part of
      the latero-dorsal telencephalon (Dla) from 7 dph onwards. CRF, ACTH, alpha-MSH,
      and cortisol were quantified by radioimmunoassays in homogenates of the anterior
      cranial region of the larvae containing brain, pituitary, and headkidneys. CRF
      contents increased from 43 +/- 3 to 1070 +/- 70 pg/larvae between 5 and 110 dph.
      Larvae of age 5, 12, 24, and 42 dph were captured sequentially from a group. All
      life stages were able to rapidly increase their cortisol content in response to
      this stressor (ANOVA: P < 0.001). Overall, the developmental stage affected
      cortisol content (ANOVA: P < 0.001), but developmental stage did not influence
      the cortisol reaction to stress (ANOVA: P > 0.162). Whole brain CRF content did
      not change during the 20 min stress period and the relationship between CRF
      producing neurons and the initial HPI stress response in early life stages
      remains to be established. Cortisol feeding of 18 and 29 dph larvae for periods
      ranging from 2 to 24 days resulted in elevations of the CRF content (P < 0.003)
      in comparison to controls. In 18 dph larvae cortisol feeding abolished the
      cortisol response to capture stress as observed in control fed larvae (P <
      0.008). We propose that cortisol induced upregulation of CRF takes place in the
      telencephalon and is restricted to a time period during larval development,
      characterised by the absence of glucocortoid receptor (GR) expression in the
      telencephalic Dm region in these larvae. Finally, the stress response to 24 h
      confinement was compared between saltwater adapted and freshwater adapted
      juveniles (age 77 dph). Confinement stress (24 h) affected cortisol and CRF
      content (ANOVA: P < 0.001, P < 0.008, respectively), but not ACTH content.
      Interactions were observed between salinity and confinement regarding cortisol
      and alpha-MSH contents (ANOVA: P < 0.02), but not regarding CRF and ACTH
      contents. The increase in cortisol levels induced by confinement was remarkably
      high in freshwater adapted larvae (five times higher than in saltwater adapted
      larvae). Regarding the cortisol response it is concluded that during and after
      the period of mouth breeding tilapia larvae respond to capture stress in a
      similar fashion (onset and height) as adults. Previously, we reported that the
      initial plasma cortisol response to capture stress in adult tilapia occurred
      independently from changes in plasma ACTH levels. The current finding that also
      brain CRF contents do not alter during the initial cortisol response in larvae
      further indicates that the initial cortisol response in this species may be
      regulated independently from CRF and ACTH.

PMID- 15560873
TI  - Production and characterization of recombinantly derived peptides and antibodies
      for accurate determinations of somatolactin, growth hormone and insulin-like
      growth factor-I in European sea bass (Dicentrarchus labrax).
AB  - A specific radioimmunoassay (RIA) for European sea bass (Dicentrarchus labrax)
      growth hormone (GH) was developed and validated. For this purpose, a stable
      source of GH was produced by means of recombinant DNA technology in a bacteria
      system. The identity of the purified protein (ion exchange chromatography) was
      demonstrated by Western blot and a specific GH antiserum was raised in rabbit. In
      Western blot and RIA system, this antiserum recognized specifically native and
      recombinant GH, and it did not cross-react with fish prolactin (PRL) and
      somatolactin (SL). In a similar way, a specific polyclonal antiserum against the
      now available recombinant European sea bass SL was raised and used in the RIA
      system to a sensitivity of 0.3 ng/ml (90% of binding of tracer). Further,
      European sea bass insulin-like growth factor-I (IGF-I) was cloned and sequenced,
      and its high degree of identity with IGF-I peptides of barramundi, tuna, and
      sparid fish allowed the use of a commercial IGF-I RIA based on barramundi IGF-I
      antiserum. These assay tools assisted for the first time accurate determinations
      of SL and GH-IGF-I axis activity in a fish species of the Moronidae family. Data
      values were compared to those found with gilthead sea bream (Sparus aurata),
      which is currently used as a Mediterranean fish model for growth endocrinology
      studies. As a characteristic feature, the average concentration year round of
      circulating GH in growing mature males of European sea bass was higher than in
      gilthead sea bream. By contrast, the average concentration of circulating SL was
      lower. Concerning to circulating concentration of IGF-I, the measured plasma
      values for a given growth rate were also lower in European sea bass. These
      findings are discussed on the basis of a different energy status that might
      allowed a reduced but more continuous growth in European sea bass.

PMID- 15560874
TI  - Emotion cognition in children and adolescents: introduction to the special issue.

PMID- 15560875
TI  - Understanding the emotional past: relations between parent and child
      contributions in emotionally negative and nonnegative events.
AB  - The past event conversations of 33 mothers with their 3-year-old children (18
      girls and 15 boys) were selected from a larger sample based on their discussion
      of negative events. Negative events included both those that were negative in
      topic and those that contained negative incidents but were otherwise positively
      themed. Within-subjects comparisons were made between the negative events and a
      neutral or positive event. There were few differences in how mothers and their
      children talked about negative and nonnegative events. Children did include more
      interpretations (internal state and causal references) in their negative event
      conversations. For both event types, mothers who talked more about the past
      events had children who reported more. When maternal talkativeness was
      controlled, involving children in the negative event conversations through
      deflecting the conversational turn predicted children's total contributions and
      number of interpretations. Repeating information and requests for information
      while constraining the topic was negatively related to the number of details
      children reported for nonnegative past events. Conversations about minor negative
      experiences demonstrate that mothers can influence children's involvement in
      discussions and understanding of the past.

PMID- 15560876
TI  - Preschoolers' effortful control and negative emotionality, immediate reactions to
      disappointment, and quality of social functioning.
AB  - Relations among effortful control/low negative emotionality, immediate reactions
      in a situation that usually calls for the masking of disappointment (i.e., the
      use of display rules), and social competence/adjustment were investigated for 78
      preschool children (mean age=4.87 years). Parents, teachers, and peers rated
      children on negative emotionality and/or effortful control as well as on social
      competence/adjustment. Children who were rated by parents and teachers as high on
      effortful control/low on negative emotionality expressed fewer immediate
      verbal/gestural indicators of disappointment in the presence of an unfamiliar
      adult and were perceived by their parents, teachers, and peers as socially
      competent and well adjusted. The pattern of findings was consistent with the view
      that children's immediate verbal/gestural reactions to disappointment partially
      mediated the relations between effortful control (as reported by parents) and
      social competence/adjustment.

PMID- 15560877
TI  - Attentional bias toward fear-related stimuli: an investigation with nonselected
      children and adults and children with anxiety disorders.
AB  - Research investigating anxiety-related attentional bias for emotional information
      in anxious and nonanxious children has been equivocal with regard to whether a
      bias for fear-related stimuli is unique to anxious children or is common to
      children in general. Moreover, recent cognitive theories have proposed that an
      attentional bias for objectively threatening stimuli may be common to all
      individuals, with this effect enhanced in anxious individuals. The current study
      investigated whether an attentional bias toward fear-related pictures could be
      found in nonselected children (n=105) and adults (n=47) and whether a sample of
      clinically anxious children (n=23) displayed an attentional bias for fear-related
      pictures over and above that expected for nonselected children. Participants
      completed a dot-probe task that employed fear-related, neutral, and pleasant
      pictures. As expected, both adults and children showed a stronger attentional
      bias toward fear-related pictures than toward pleasant pictures. Consistent with
      some findings in the childhood domain, the extent of the attentional bias toward
      fear-related pictures did not differ significantly between anxious children and
      nonselected children. However, compared with nonselected children, anxious
      children showed a stronger attentional bias overall toward affective picture
      stimuli.

PMID- 15560878
TI  - Adolescents' emotion expectancies regarding aggressive and nonaggressive events:
      connections with behavior problems.
AB  - A total of 50 behaviorally disruptive (conduct-disordered or oppositional defiant
      disordered) adolescents and 50 comparison adolescents assessed how they expected
      to feel following both aggressive and nonaggressive situations. Compared with
      their peers, behaviorally disruptive adolescents expected fewer normative
      emotions and exhibited somewhat more of an anger emphasis in their nonaggressive
      emotion attributions, and they expected to feel happier following acts of
      instrumental/proactive aggression. These patterns of emotion expectancies were
      linked more closely with teacher ratings of adolescents' proactive aggression
      than with ratings of reactive aggression. Regression analyses indicated that both
      nonaggression emotion expectancies and proactive aggression happiness made
      independent contributions to predicting adolescents' externalizing tendencies.
      Discussion focused on the contributions of different types of self-attributed
      emotion expectancies to adolescents' social understanding and behavior.

PMID- 15560879
TI  - Migration, mental health, and human rights.

PMID- 15560880
TI  - Part I--the mental health impacts of migration: the law and its effects failing
      to understand: refugee determination and the traumatized applicant.

PMID- 15560881
TI  - Australia's human rights obligations relating to the mental health of refugee
      children in detention.

PMID- 15560882
TI  - Locations of care: meeting the mental health and social care needs of refugees in
      Europe.

PMID- 15560883
TI  - Part II--movement and stasis: re-reading refugee and migration laws immigration
      mindsets--how our thinking has shaped migration law in Australia.

PMID- 15560884
TI  - The madness of migration: disquiet in the international law relating to refugees.

PMID- 15560885
TI  - Foreigners and the right to justice in the aftermath of 9/11.

PMID- 15560886
TI  - Part III--rights and remedies: the convention against torture alternative asylum
      mechanisms: the convention against torture and other cruel, inhuman or degrading
      treatment or punishment.

PMID- 15560887
TI  - Torturing terrorists after September 11.

PMID- 15560888
TI  - The activities of several detoxication enzymes are differentially induced by
      juices of garden cress, water cress and mustard in human HepG2 cells.
AB  - It has been previously demonstrated in a human-derived hepatoma cell line (HepG2)
      that juices from cruciferous vegetables protect against the genotoxicity caused
      by dietary carcinogens. HepG2 cells possess different enzymes involved in the
      biotransformation of xenobiotics. Therefore, we investigated the effect of
      cruciferous juices on the activities of CYP 1A and several phase II enzymes in
      this cell model. For each experiment, 1 x 10(6) cells were seeded on Petri
      dishes. After 2 days, the juices (0.5-8 microl/ml of culture medium) were added
      for 48 h prior to cell harvesting. The addition of juice from water cress
      (Nasturtium officinalis R. Br) significantly increased the activities of
      ethoxyresorufin-O-deethylase at high doses only and NAD(P)H-quinone reductase in
      a dose-dependent manner (1.8- and 5-fold, respectively). The addition of juice
      from garden cress (Lepidum sativum L.) significantly increased the activities of
      NAD(P)H-quinone reductase and UDP-glucuronosyl-transferase with a maximal effect
      around the dose of 2 microl/ml juice (1.4- and 1.2-fold, respectively) while the
      other enzymes were not altered. Mustard (Sinapis alba L.) juice increased the
      activities of NAD(P)H-quinone reductase (2.6-fold at the dose of 8 microl/ml),
      and N-acetyl-transferase (1.4-fold at the dose of 8 microl/ml) in a dose
      dependent manner while a maximal induction of UDP-glucuronosyl-transferase was
      obtained with a dose of 2 microl/ml (1.8-fold). These observations show that the
      three juices have different induction profiles: only water cress acted as a
      bifunctional inducer by enhancing both phase I and phase II enzymes. As a
      consequence, each juice may preferentially inhibit the genotoxicity of specific
      compounds.

PMID- 15560889
TI  - In vitro metabolism of carbofuran by human, mouse, and rat cytochrome P450 and
      interactions with chlorpyrifos, testosterone, and estradiol.
AB  - Carbofuran is a carbamate pesticide used in agricultural practice throughout the
      world. Its effect as a pesticide is due to its ability to inhibit
      acetylcholinesterase activity. Though carbofuran has a long history of use, there
      is little information available with respect to its metabolic fate and
      disposition in mammals. The present study was designed to investigate the
      comparative in vitro metabolism of carbofuran from human, rat, and mouse liver
      microsomes (HLM, RLM, MLM, respectively), and characterize the specific enzymes
      involved in such metabolism, with particular reference to human metabolism.
      Carbofuran is metabolized by cytochrome P450 (CYP) leading to the production of
      one major ring oxidation metabolite, 3-hydroxycarbofuran, and two minor
      metabolites. The affinity of carbofuran for CYP enzymes involved in the oxidation
      to 3-hydroxycarbofuran is significantly less in HLM (Km=1.950 mM) than in RLM
      (Km=0.210 mM), or MLM (Km=0.550 mM). Intrinsic clearance rate calculations
      indicate that HLM are 14-fold less efficient in the metabolism of carbofuran to 3
      hydroxycarbofuran than RLM or MLM. A screen of 15 major human CYP isoforms for
      metabolic ability with respect to carbofuran metabolism demonstrated that CYP3A4
      is the major isoform responsible for carbofuran oxidation in humans. CYP1A2 and
      2C19 are much less active while other human CYP isoforms have minimal or no
      activity toward carbofuran. In contrast with the human isoforms, members of the
      CYP2C family in rats are likely to have a primary role in carbofuran metabolism.
      Normalization of HLM data with the average levels of each CYP in native HLM,
      indicates that carbofuran metabolism is primarily mediated by CYP3A4 (percent
      total normalized rate (% TNR)=77.5), although CYP1A2 and 2C19 play ancillary
      roles (% TNR=9.0 and 6.0, respectively). This is substantiated by the fact that
      ketoconazole, a specific inhibitor of CYP3A4, is an excellent inhibitor of 3
      hydroxycarbofuran formation in HLM (IC50: 0.31 microM). Chlorpyrifos, an
      irreversible non-competitive inhibitor of CYP3A4, inhibits the formation of 3
      hydroxycarbofuran in HLM (IC50: 39 microM). The use of phenotyped HLM
      demonstrated that individuals with high levels of CYP3A4 have the greatest
      potential to metabolize carbofuran to its major metabolite. The variation in
      carbofuran metabolism among 17 single-donor HLM samples is over 5-fold and the
      best correlation between CYP isoform activity and carbofuran metabolism was
      observed with CYP3A4 (r2=0.96). The interaction of carbofuran and the endogenous
      CYP3A4 substrates, testosterone and estradiol, were also investigated.
      Testosterone metabolism was activated by carbofuran in HLM and CYP3A4, however,
      less activation was observed for carbofuran metabolism by testosterone in HLM and
      CYP3A4. No interactions between carbofuran and estradiol metabolism were
      observed.

PMID- 15560890
TI  - Extracts from cigarette smoke induce DNA damage and cell adhesion molecule
      expression through different pathways.
AB  - Cigarette smoke is a major risk factor for human diseases, such as lung cancer
      and atherosclerosis. The present study was undertaken to investigate the effect
      of non-fractionated water-soluble cigarette smoke extract (NFWS CSE) on DNA
      damage and cellular adhesion molecule expression in human umbilical vein
      endothelial cells (HUVECs). DNA damage and the surface expression of
      intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by the
      use of the comet assay and flow cytometry, respectively. NFWS CSE-induced DNA
      damage in a dose-dependent manner during a 2 h exposure. Pretreatment with
      ascorbic acid or alpha-tocopherol completely inhibited the NFWS CSE-induced DNA
      damage. NFWS CSE exposure also up-regulated the surface expression of ICAM-1 and
      E-selectin in HUVECs. Pretreatment with ascorbic acid or alpha-tocopherol had no
      effect on NFWS CSE-induced E-selectin and ICAM-1 expression. In contrast, the non
      antioxidant metal chelator 1,10-phenanthroline partially suppressed the surface
      expression of ICAM-1 and E-selectin. These results suggest that NFWS CSE exposure
      induces both DNA damage and the surface expression of adhesion molecules in
      HUVECs. However, the molecular mechanism of these effects may be through
      different pathways: reactive oxygen species are involved in NFWS CSE-induced DNA
      damage but have little relation to NFWS CSE-induced E-selectin and ICAM-1
      expression.

PMID- 15560891
TI  - Neo-clerodane diterpenoid, a new metalloprotease snake venom inhibitor from
      Baccharis trimera (Asteraceae): anti-proteolytic and anti-hemorrhagic properties.
AB  - Many plants are used in traditional medicine as active agents against various
      effects induced by snakebite. Few attempts have been made however to identify the
      nature of plant natural products with anti-ophidian properties. Baccharis trimera
      (Less) DC (Asteraceae), known in Brazil as carqueja, has been popularly used to
      treat liver diseases, rheumatism, diabetes, as well as digestive, hepatic and
      renal disorders. The active component was identified as 7alpha-hydroxy-3,13
      clerodadiene-16,15:18,19-diolide, C20H28O5, (clerodane diterpenoid, Bt-CD). We
      report now the anti-proteolytic and anti-hemorrhagic properties against snake
      venoms of a Bt-CD inhibitor from B. trimera. Bt-CD exhibited full inhibition of
      hemorrhage and proteolytic activity caused by Bothrops snake venoms. The
      inhibitor was able to neutralize the hemorrhagic, fibrinogenolytic and
      caseinolytic activities of class P-I and III metalloproteases isolated from B.
      neuwiedi and B. jararacussu venoms. No inhibition of the coagulant activity was
      observed. Bt-CD also partially inhibited the edema induced by other crude venoms,
      metalloproteases, basic and acidic phospholipases A2. To further elucidate the
      inhibitory specificity of Bt-CD against metalloproteases isolated from snake
      venoms, a deeper understanding of its structure and function is necessary.
      Furthermore, the potential use of these inhibitors to complement anti-venom as an
      alternative treatment of snakebite envenomations needs to be evaluated in future
      studies.

PMID- 15560892
TI  - Cd2+ versus Ca2+-produced mitochondrial membrane permeabilization: a proposed
      direct participation of respiratory complexes I and III.
AB  - A comparison of Cd2+ and Ca2+ effects on in vitro rat liver mitochondria function
      and a further study of their interaction were conducted. Similarity and
      distinction in action of rotenone, oligomycin, N-ethylmaleimide, dithiothreitol,
      catalase, dibucaine, ruthenium red, cyclosporin A (CsA), and ADP on Cd2+ and/or
      Ca2+-induced mitochondrial dysfunction were revealed. We found that rotenone
      exerted a strong protective action both against Ca2+ and Cd2+-produced
      mitochondrial membrane permeabilization (MMP). In contrast to Ca2+, catalase and
      dibucaine did not influence on main Cd2+ effects. In NH4NO3 medium N
      ethylmaleimide (NEM) at low concentrations increased markedly Cd2+-produced
      swelling of non-energized mitochondria, whereas it exhibited a partial reversal
      effect following energization. In sucrose medium low [NEM] did not change Cd2+
      produced mitochondrial swelling. High [NEM] promoted synergistic increase of the
      Cd2+-produced swelling in NH4NO3 medium; all above effects were reversed (and
      prevented) by dithiothreitol, DTT. We shown also that when exogenous Ca2+ and Pi
      were simultaneously present in NH4NO3 medium, DTT reversed only partially Cd2+
      produced swelling of succinate plus rotenone-energized mitochondria, while DTT
      recovery action was complete when either Ca2+ or Pi were separately administered
      to the Cd2+-treated mitochondria. Besides, DTT added following a low Cd2+ pulse
      in KCl medium containing exogenous Ca2+ induced a substantial enhancing of
      sustained Cd2+ stimulation of mitochondrial basal respiration and the stimulation
      was CsA-sensitive, while the activation promoted by low [Cd2+] alone was totally
      eliminated by DTT supplement. We observed the similar respiratory activation
      earlier when high concentrations of Cd2+ in the absence of added Ca2+ were used
      but it was completely CsA-insensitive. A possible involvement of respiratory
      chain components, namely complex I (P-site) and complex III (S-site) in Cd2+
      and/or Ca2+-produced MMP was discussed.

PMID- 15560893
TI  - Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage.
AB  - Ethylbenzene is carcinogenic to rats and mice, while it has no mutagenic
      activity. We have investigated whether ethylbenzene undergoes metabolic
      activation, leading to DNA damage. Ethylbenzene was metabolized to 1
      phenylethanol, acetophenone, 2-ethylphenol and 4-ethylphenol by rat liver
      microsomes. Furthermore, 2-ethylphenol and 4-ethylphenol were metabolically
      transformed to ring-dihydroxylated metabolites such as ethylhydroquinone and 4
      ethylcatechol, respectively. Experiment with 32P-labeled DNA fragment revealed
      that both ethylhydroquinone and 4-ethylcatechol caused DNA damage in the presence
      of Cu(II). These dihydroxylated compounds also induced the formation of 8-oxo-7,8
      dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of Cu(II). Catalase,
      methional and Cu(I)-specific chelator, bathocuproine, significantly (P<0.05)
      inhibited oxidative DNA damage, whereas free hydroxyl radical scavenger and
      superoxide dismutase did not. These results suggest that Cu(I) and H2O2 produced
      via oxidation of ethylhydroquinone and 4-ethylcatechol are involved in oxidative
      DNA damage. Addition of an endogenous reductant NADH dramatically enhanced 4
      ethylcatechol-induced oxidative DNA damage, whereas ethylhydroquinone-induced DNA
      damage was slightly enhanced. Enhancing effect of NADH on oxidative DNA damage by
      4-ethylcatechol may be explained by assuming that reactive species are generated
      from the redox cycle. In conclusion, these active dihydroxylated metabolites
      would be involved in the mechanism of carcinogenesis by ethylbenzene.

PMID- 15560894
TI  - Characterization of the B2 receptor and activity of bradykinin analogs in SHP-77
      cell line by Cytosensor microphysiometer.
AB  - The Cytosensor microphysiometer device (Molecular Devices, Sunnyvale, CA) is
      capable of measuring the rate at which cells acidify their environment in
      response to ligand-receptor binding. By measuring the extracellular acidification
      response (ECAR) we characterized some aspects of ligand-B2 receptor interaction
      in SHP-77 cell line. SHP-77 cells maximally acidified their environment within 30
      s after the exposure to bradykinin (BK) or the BK agonist, B9972, with the
      maximum effect seen at a ligands concentration of 1 microM. Fetal bovine serum
      (FBS) modulated the binding of BK or B9972, showing that B9972 is a partial
      agonist. In addition, the binding of BK agonist or antagonist to the B2 receptor
      showed different ECAR and different interaction with other intracellular and
      plasma membrane proteins. Our microphysiometrical results showed that two
      parameters, antagonist binding affinity (pD2) and antagonist potency (pIC50) are
      required to characterize BK antagonist activity for the B2 receptor in the SHP-77
      cell line. The previously used parameter of B2 antagonist activity, pA2, had high
      variation and poor correlation with the inhibition of SHP-77 cell growth in vitro
      and suppression of tumor growth when SHP-77 cells were injected to mice. Our
      results permit us to conclude that BK agonists and antagonists differ in their
      interactions with the B2 receptor and consequently elicit different cell
      responses. Based on our results, we have developed a new microphysiometrical
      assay for analyzing the activity of BK agonists and antagonist in SHP-77 cells,
      which may facilitate the discovery of new potent anticancer drugs.

PMID- 15560895
TI  - New monthly publication.

PMID- 15560896
TI  - Evaluation of healing by gentle touch.
AB  - OBJECTIVES: To evaluate the effectiveness and safety of healing by gentle touch
      in clients attending The Centre for Complementary Care (CCC) in Eskdale, Cumbria.
      STUDY DESIGN: An evaluation of data collected by questionnaire over 6 years.
      METHODS: All clients attending the CCC between 1995 and 2001 were invited to
      participate in this study, and data were collected from 300 subjects with a wide
      range of ailments who received four treatment sessions within 6 weeks. Exclusion
      criteria were: recent treatment at the CCC; failure to complete four treatment
      sessions; and age under 16 years. Outcome measures included comparison of pre-
      and post-treatment levels of physical (pain, disability, immobility, sleep
      disturbances, reliance upon medication, daily activities) and psychological
      (stress, panic, fear, anger, relaxation, coping, depression/anxiety) functioning;
      these were assessed using a questionnaire with visual analogue scales for
      subjective rating of symptoms and the EuroQoL (EQ-5D), a generic state-of-health
      measure. RESULTS: Wilcoxon signed ranks tests showed statistically significant
      improvements in both psychological and physical functioning, particularly in
      stress reduction (median stress levels fell by four points), pain relief (median
      pain ratings fell by two points), increased ability to cope (median improvement
      of three points) and increased general health ratings (median improvement of 20
      points) between study entry and end of treatment (P < 0.0004 for all these
      symptoms). The most substantial improvements were seen in those with the most
      severe symptoms at study entry. No adverse effects of treatment were documented.
      CONCLUSIONS: This audit of treatment outcomes provides evidence consistent with
      the hypothesis that healing, as provided at the CCC, was associated with improved
      psychological and physical functioning in the majority of subjects, and is worthy
      of further evaluation.

PMID- 15560897
TI  - Health departments' implementation of public health's core functions: an
      assessment of health impacts.
AB  - OBJECTIVES: The purpose of this article was to investigate the relationship
      between state health agencies' adherence to the recommendations of the United
      State's Institute of Medicine's (IOM) report, "The Future of Public Health", and
      changes in their populations' health. STUDY DESIGN: Data were abstracted from
      agencies' plans, budgets, annual reports, etc. spanning a 5-year period. A
      comprehensive change in population health measure over the same period was drawn
      from the UnitedHealth Group's annual survey. METHODS: Configurations, based on
      public health core functions, were established using linear regression and
      qualitative comparative analysis. The dependent variable was a holistic measure
      of change in a state population's health status. RESULTS: State agencies that
      most completely adopted a public health model emphasizing assessment, assurance
      and policy development also experienced significant improvements in their
      population health measures. CONCLUSIONS: State agencies that more completely
      adopted the IOM's public health core functions had a concomitant improvement in
      their populations' health statuses. Further research to explore if there is a
      causal link between adoption of the core functions and positive health impacts is
      warranted.

PMID- 15560898
TI  - Specialist public health capacity in England: working in the new primary care
      organizations.
AB  - OBJECTIVES: To determine the capacity and development needs, in relation to key
      areas of competency and skills, of the specialist public health workforce based
      in primary care organizations following the 2001 restructuring of the UK National
      Health Service. STUDY DESIGN: Questionnaire survey to all consultants and
      specialists in public health (including directors of public health) based in
      primary care trusts (PCTs) and strategic health authorities (SHAs) in England.
      RESULTS: Participants reported a high degree of competency. However, skill gaps
      were evident in some areas of public health practice, most notably "developing
      quality and risk management" and in relation to media communication, computing,
      management and leadership. In general, medically qualified individuals were
      weaker on community development than non-medically qualified specialists, and non
      medically qualified specialists were less able to perform tasks that require
      epidemiological or clinical expertise than medically qualified specialists. Less
      than 50% of specialists felt that their links to external organizations,
      including public health networks, were strong. Twenty-nine percent of respondents
      felt professionally isolated and 22% reported inadequate team working within
      their PCT or SHA. Approximately 21% of respondents expressed concerns that they
      did not have access to enough expertise to fulfil their tasks and that their
      skills were not being adequately utilized. CONCLUSIONS: Some important skill gaps
      are evident among the specialist public health workforce although, in general, a
      high degree of competency was reported. This suggests that the capacity deficit
      is a problem of numbers of specialists rather than an overall lack of appropriate
      skills. Professional isolation must be addressed by encouraging greater
      partnership working across teams.

PMID- 15560899
TI  - Mind the gap: developing the PH workforce in the North East and Yorkshire and
      Humber regions: a scoping stakeholder study.
AB  - OBJECTIVES: The aim of this study was to identify key issues around public health
      workforce development in the North of England, considering the gap between need
      and current capacity and the training requirements to deliver the public health
      and health improvement agenda. METHODS: Interviews were carried out with over 50
      professionals in a variety of stakeholder organizations, seeking their views on
      priorities for workforce development and perceived opportunities and threats to
      the development of a good public health workforce. RESULTS: There was general
      recognition of a gap between current public health resources and what is needed
      to meet the public health agenda. Priorities included both increasing capacity at
      the specialist end of public health and raising general public health awareness
      at all levels of public organizations. Major barriers identified to meeting these
      needs included organizational difficulties, professional barriers and shortages
      of appropriate training and resources. Opportunities were seen to be presented by
      the increased amount of joint working and by national and local raising of
      awareness of public health issues. CONCLUSIONS: Across the health sector, local
      authorities, training organizations and voluntary sectors, similar issues and
      expectations were mentioned at both specialist and practitioner levels. However,
      it has not been possible in North East England to translate this finding into
      practical programmes in the absence of nationally identified resources to address
      the issue.

PMID- 15560900
TI  - What do other local providers think of NHS walk-in centres? Results of a postal
      survey.
AB  - OBJECTIVES: To ascertain the views of other providers of primary and emergency
      healthcare services about their local walk-in centre. DESIGN: Postal survey.
      SETTING AND PARTICIPANTS: National Health Service healthcare providers (general
      practitioners (GPs), practice nurses, pharmacists, Accident and Emergency (A and
      E) consultants) working in close proximity to 20 English walk-in centres.
      RESULTS: The overall response rate to the survey was 79% (n = 1591). Nearly one
      third of respondents felt that patient expectations had increased since their
      local walk-in centre opened, although this varied across the different sites.
      Some providers had noticed a reduction in their workload, but 15% claimed that
      workloads had increased since their local walk-in centre opened. There was broad
      agreement that these new centres did address issues of access and that they
      provided appropriate care of a reasonable quality. Communication between walk-in
      centres and other local healthcare providers was an area of considerable concern;
      GPs, in particular, were anxious about the impact of the service on continuity of
      care. There were clear differences of opinion between different types of health
      professional, with doctors tending to be more critical and practice nurses being
      more supportive. CONCLUSION: It has been suggested that healthcare professionals,
      notably GPs, are universally opposed to the concept of walk-in centres. This
      survey shows that opinions were divided, but overall, more local providers were
      in favour of this new service than were opposed to it. There was more support for
      centres co-located with A and E departments than "shop-front"-type facilities,
      but there were concerns that the service offered was too limited. The success or
      otherwise of the walk-in centre initiative will depend, in part, on building good
      relationships between the centres and other local providers. Understanding the
      views of local providers is important for those developing walk-in centres, and
      for those engaged in planning services in the wider health economies where these
      services are placed.

PMID- 15560901
TI  - Gender differences in healthcare utilization and medical indicators among
      patients with diabetes.
AB  - OBJECTIVE: To describe differences in healthcare utilization and health
      indicators of patients with diabetes, according to gender. STUDY DESIGN: A
      population-based outcome study conducted on 21,277 diabetic patients between the
      ages of 45 and 64 years who are members of the second largest health maintenance
      organization in Israel. METHODS: Data on healthcare utilization (process
      indicators) and health problems (outcome indicators) were obtained from
      computerized medical records that are stored routinely by the organization. The
      study period was the year 2002. RESULTS: Significantly (P < 0.05) lower
      healthcare utilization was observed in men compared with women for all indicators
      examined (number of visits to physicians and the performance of urine, lipids and
      creatinine tests). Nonetheless, men showed better health outcomes (lower low
      density lipoprotein cholesterol, triglycerides, HbA1c). CONCLUSIONS: Women who
      suffer from diabetes use more healthcare services and have a higher morbidity
      rate compared with men. Future research should seek to identify the factors
      contributing to this observation, which can potentially make an important
      contribution to the development of disease management strategies that target
      diabetic women.

PMID- 15560902
TI  - Areca quid chewing and methamphetamine use in Taiwanese adolescents.
AB  - The association between areca quid chewing and methamphetamine (MAMP) use in
      Taiwanese adolescents was examined in 200 MAMP users and 400 non-users. Subjects
      were interviewed individually regarding the experience of chewing areca quid and
      the evidence of lifetime areca quid use disorder. The ages at which they
      initially chewed areca quid and used MAMP were also evaluated. The results
      revealed that areca quid chewing and areca quid use disorders were more common in
      both male and female MAMP users than in non-users. Among those who chewed areca
      quid and used MAMP, the mean age at initial MAMP use was older than the mean age
      at initial chewing of areca quid in males but not in females. MAMP users who
      chewed areca quid were subdivided into three groups according to the sequence of
      initial MAMP use and chewing areca quid. Although most males and females started
      chewing areca quid before using MAMP, this pattern was more prevalent in males.
      Adolescent MAMP users need to be educated about deleterious health sequelae
      caused by chewing areca quid. Adolescent areca quid chewers need to be monitored
      for possible progression to MAMP use.

PMID- 15560903
TI  - Lifestyle-related risks: are trends in Europe converging?
AB  - OBJECTIVES: What has become of lifestyle differences in a united Europe, where
      member states become more and more similar on aspects such as welfare systems and
      population dynamics? In this paper, we try to answer the question whether the gap
      in lifestyle-related risk factors in Europe has narrowed over the past 30-40
      years. METHODS: Smoking, alcohol consumption, physical activity, obesity and food
      consumption all have an impact on cancer, cardiovascular disease and other non
      communicable diseases. Databases of Eurostat, OECD (Organisation for Economic Co
      operation and Development) and the World Health Organisation were screened for
      data on lifestyle-related risk factors in the European Union, and a literature
      search was performed for studies that collected international comparable data
      about the selected factors. RESULTS: The gap in European lifestyle has narrowed
      over the past 30-40 years for smoking (women), alcohol consumption and total fat
      intake. For fruit and vegetable consumption, convergence is not occurring. For
      some risk factors, such as smoking and obesity, intranational differences surpass
      the international differences. CONCLUSIONS: The results support the notion of
      convergent lifestyles among Europeans over time. We also found that there is a
      serious lack of reliable data on lifestyle-related risk factors that are suitable
      for international comparison. It is essential to invest in reliable and
      internationally comparable data, obtained according to best evidence, to get more
      insight into real differences regarding risk factors in Europe. The European
      Public Health programme may be an opportunity to realize these goals.

PMID- 15560904
TI  - Chemical incidents: are we ready in the West Midlands? Testing the communication
      arrangements of on-call public health doctors.
AB  - Primary care trusts are responsible for handling major chemical hazards. This
      includes the testing and exercising of plans in a regular and routine manner. The
      Chemical Hazards and Poisons Division (Birmingham), which provides a 24-h, 365
      day resource for the West Midlands region in the UK, undertook an audit to test
      the out-of-hours communication arrangements of public health doctors. The audit
      revealed that there is an urgent need to: (1) review contact details within on
      call packs; (2) ensure that doctors performing on-call duties know, at the very
      least, the names of the primary care trusts/local authorities, county
      councils/other trusts in the area; and (3) ensure a failsafe method for
      contacting the person on call for public health.

PMID- 15560905
TI  - Relationship between economic development and suicide mortality: a global cross
      sectional analysis in an epidemiological transition perspective by Moniruzzaman
      and Andersson (Public Health 118 (5), 346-348).

PMID- 15560907
TI  - Remarks on antipredator behavior and food chain dynamics.
AB  - When consumers feeding on a resource spend time in avoiding high risks of
      predation, the predator functional response declines with predator density. While
      this is well established, less attention has been paid to the dependence of the
      consumer functional response on predator density. Here we show how the separation
      of behavioral and ecological timescales allows one to determine both responses
      starting from an explicit behavioral model. Within the general set-up considered
      in this paper, the two functional responses can tend toward Holling type II
      responses when consumers react only weakly to predation. Thus, the main
      characteristics of the standard Rosenzweig-MacArthur tritrophic food chain
      (logistic resource and Holling type II consumer and predator) remain valid also
      when consumers have weak antipredator behavior. Moreover, through numerical
      analysis, we show that in a particular but interesting case pronounced
      antipredator behaviors stabilize the system.

PMID- 15560908
TI  - Kin selection and coefficients of relatedness in family-structured populations
      with inbreeding.
AB  - We consider family specific fitnesses that depend on mixed strategies of two
      basic phenotypes or behaviours. Pairwise interactions are assumed, but they are
      restricted to occur between sibs. To study the change in frequency of a rare
      mutant allele, we consider two different forms of weak selection, one applied
      through small differences in genotypic values determining individual mixed
      strategies, the other through small differences in viabilities according to the
      behaviours chosen by interacting sibs. Under these two specific forms of weak
      selection, we deduce conditions for initial increase in frequency of a rare
      mutant allele for autosomal genes in the partial selfing model as well as
      autosomal and sex-linked genes in the partial sib-mating model with selection
      before mating or selection after mating. With small differences in mixed
      strategies, we show that conditions for protection of a mutant allele are
      tantamount to conditions for initial increase in frequency obtained in additive
      kin selection models. With particular reference to altruism versus selfishness,
      we provide explicit ranges of values for the selfing or sib-mating rate based on
      a fixed cost-benefit ratio and the dominance scheme that allow the spreading of a
      rare mutant allele into the population. This study confirms that more inbreeding
      does not necessarily promote the evolution of altruism. Under the hypothesis of
      small differences in viabilities, the situation is much more intricate unless an
      additive model is assumed. In general however, conditions for initial increase in
      frequency of a mutant allele can be obtained in terms of fitness effects that
      depend on the genotypes of interacting individuals or their mates and generalized
      conditional coefficients of relatedness according to the inbreeding condition of
      the interacting individuals.

PMID- 15560909
TI  - Rational behavioral response and the transmission of STDs.
AB  - The susceptible-infected (SI) model is extended by allowing for individual
      optimal choices of self-protective actions against infection, where agents differ
      with respect to preferences and costs of self-protection. It is shown that a
      unique endemic equilibrium prevalence exists when the basic reproductive number
      of a STD is strictly greater than unity, and that the disease-free equilibrium is
      the unique steady state equilibrium when the basic reproductive number is less
      than or equal to one. Unlike in models that take individual behavior as given and
      fixed, the endemic equilibrium prevalence need not vary monotonically with
      respect to the basic reproductive number. Specifically, with endogenously
      determined self-protective behavior, a reduction in the basic reproductive number
      may in fact increase the endemic equilibrium prevalence. The global stability of
      the endemic steady state is established for the case of a homogeneous population
      by showing that, for any non-zero initial disease prevalence, there exists an
      equilibrium path which converges to the endemic steady state.

PMID- 15560910
TI  - On the meaning of non-epistatic selection.
AB  - In population genetics, the additive and multiplicative viability models are
      often used for the quantitative description of models in which the genetic
      contributions of several different loci are independent; that is, there is no
      epistasis. Non-epistasis may also be quantitatively defined in terms of measures
      of interaction used widely in statistics. Setting these measures of epistasis to
      zero yields alternative definitions of non-epistasis. We show here that these two
      definitions of non-epistasis are equivalent; that is, in the most general case of
      a multilocus, multiallele system, the additive and multiplicative viability
      models are unique solutions of the additive and multiplicative conditions,
      respectively, for non-epistasis.

PMID- 15560911
TI  - Stoichiometry and food-chain dynamics.
AB  - Traditional models of chemostat systems looking at interactions between predator,
      prey and nutrients have used only a single currency, such as energy or nitrogen.
      In reality, growth of autotrophs and heterotrophs may be limited by various
      elements, e.g. carbon, nitrogen, phosphorous or iron. In this study we develop a
      dynamic energy budget model chemostat which has both carbon and nitrogen as
      currencies, and examine how the dual availability of these elements affects the
      growth of phytoplankton, trophic transfer to zooplankton, and the resulting
      stability of the chemostat ecosystem. Both species have two reserve pools to
      obtain a larger metabolic flexibility with respect to changing external
      environments. Mineral nitrogen and carbon form the base of the food chain, and
      they are supplied at a constant rate. In addition, the biota in the chemostat
      recycle nutrients by means of respiration and excretion, and organic detritus is
      recycled at a fixed rate. We use numerical bifurcation analysis to assess the
      model's dynamic behavior. In the model, phytoplankton is nitrogen limited, and
      nitrogen enrichment can lead to oscillations and multiple stable states.
      Moreover, we found that recycling has a destabilizing effect on the food chain
      due to the increased repletion of mineral nutrients. We found that both carbon
      and nitrogen enrichment stimulate zooplankton growth. Therefore, we conclude that
      the concept of single-element limitation may not be applicable in an ecosystem
      context.

PMID- 15560912
TI  - Competitive coexistence in a dynamic landscape.
AB  - This paper investigates the effect of a dynamic landscape on the persistence of
      many interacting species. We develop a multi-species community model with an
      evolving landscape in which the creation and destruction of habitat are dynamic
      and local in space. Species interactions are also local involving hierarchical
      competitive trade-offs. We show that dynamic landscapes can reverse the trend of
      increasing species richness with higher fragmentation observed in static
      landscapes. The increase in the species-area exponent from a homogeneous to a
      fragmented landscape does not occur when dynamics are turned on. Thus, temporal
      aspects of the processes that generate and destroy habitat appear dominant
      relative to spatial characteristics. We also demonstrate, however, that temporal
      and spatial aspects interact to influence the persistence time of individual
      species, and therefore, rank-abundance curves. Specifically, persistence in the
      model increases in habitats with faster local turnover because of the presence of
      dynamic corridors.

PMID- 15560913
TI  - Asymptotic behavior of joint distributions of characteristics of a pair of
      randomly chosen individuals in discrete-time Fisher-Wright models with mutations
      and drift.
AB  - This is a continuation of the series of articles (C.R. Rao, D.N. Shanbhag (Eds.),
      Handbook of Statistics 19: Stochastic Processes: Theory and Methods, Elsevier
      Science, Amsterdam, 2001 (Chapter 8); Math. Biosci. 175 (2002) 83; Math. Meth.
      Appl. Sci. 26 (2003) 1587; Adv. Appl. Probab. 36 (2004) 57) devoted to a study of
      the interplay between two of the main forces of population genetics, mutations
      and drift, in the Fisher-Wright model. We provide discrete-time versions of
      theorems describing asymptotic behavior of joint distributions of characteristics
      of a pair of individuals in this model; their continuous-time counterparts were
      presented in the previous papers. Furthermore, we show that imbalance index,
      introduced in Kimmel et al. (Genetics 148 (1998) 1921) and King et al. (Mol.
      Biol. Evol. 17(12) (2000) 1895) in the context of continuous-time models, may
      also be used in discrete-time models to detect past population growth.

PMID- 15560914
TI  - Conditional dispersal under kin competition: extension of the Hamilton-May model
      to brood size-dependent dispersal.
AB  - I consider a site-based model with contest competition among siblings, and assume
      that dispersal is conditional on the number of offspring in the natal site.
      Evolutionarily stable populations contain threshold dispersal strategies, which
      retain a certain number of offspring in the natal site and disperse the rest (if
      the actual number of offspring is less than the threshold, then all offspring are
      retained). Due to the discrete nature of the strategy set (the threshold must be
      integer), the ESS may not be unique or may not exist. In the latter case, two
      neighboring threshold strategies coexist in the evolutionarily stable population.
      Dispersal first decreases and then increases as a function of dispersal
      mortality, such that all but one offspring should be dispersed both when
      dispersal mortality is very small or very high. Population-level dispersal
      fractions are often similar to the unconditional ESS, but differ strongly when
      fecundity is small and dispersal mortality is high.

PMID- 15560915
TI  - Polyploid and multilocus extensions of the Wahlund inequality.
AB  - Wahlund's inequality informally states that if a structured and an unstructured
      population have the same allele frequencies at a locus, the structured population
      contains more homozygotes. We show that this inequality holds generally for
      ploidy level P, that is, the structured population has more P-polyhomozygotes.
      Further, for M randomly chosen loci (M >or= 2), the structured population is also
      expected to contain more M-multihomozygotes than an unstructured population with
      the same single-locus homozygosities. The extended inequalities suggest
      multilocus identity coefficients analogous to F(ST). Using microsatellite
      genotypes from human populations, we demonstrate that the multilocus Wahlund
      inequality can explain a positive bias in "identity-in-state excess".

PMID- 15560916
TI  - Proceedings of the 7th International Symposium on Instrumental Analysis.
      September 21-24, 2003. Pecs, Hungary. Symposium dedicated to Professor Stellan
      Hjerten on the occasion of his 75th birthday.

PMID- 15560917
TI  - Enantioseparation of dipeptides and tripeptides by micro-HPLC comparing
      teicoplanin and teicoplanin aglycone as chiral selectors.
AB  - Chiral separation of glycyl- and diastereomeric dipeptides and tripeptides was
      performed by micro-HPLC using macrocyclic antibiotics as chiral selectors.
      Teicoplanin was compared with teicoplanin aglycone (TAG) regarding selectivity,
      efficiency and separation time. The stationary phases are based on teicoplanin
      and TAG chemically bonded to 3.5 mum silica gel. The material was packed into 10
      cm x 1 mm stainless steel microcolumns. Different mobile phases were checked
      using the reversed phase mode. Both teicoplanin and TAG were found to show good
      chiral separation ability for dipeptides. Glycyl-dipeptides were baseline
      resolved and most of the diastereomeric dipeptides and tripeptides were separated
      into their four isomers. In this study, teicoplanin was found to be advantageous
      compared to TAG regarding separation time, although TAG showed the higher
      resolution power. Baseline resolution for some glycyl-dipeptides was obtained
      within 3 min, diastereomeric dipeptides were resolved in 7 min. This method was
      also shown to be applicable for enantiomer purity control.

PMID- 15560918
TI  - Chiral separation of natural and unnatural amino acid derivatives by micro-HPLC
      on a Ristocetin A stationary phase.
AB  - This paper deals with the chiral separation of Fmoc- and Z-derivatives of natural
      and unnatural sulfur containing amino acids by micro-HPLC. The separations were
      carried out in microbore columns packed with a new material based on Ristocetin A
      bonded to 3.5 microm silica gel. The columns were run in the normal phase, polar
      organic mode as well as in the reversed phase mode, whereby best results were
      obtained with the reversed-phase mode using mixtures of triethylamine acetate
      (TEAA) buffer and methanol as mobile phases.

PMID- 15560919
TI  - Determination of 4-amino-m-cresol and 5-amino-o-cresol and metabolites in human
      keratinocytes (HaCaT) by high-performance liquid chromatography with DAD and MS
      detection.
AB  - A multi-step gradient HPLC system combined with DAD and MS detection has been
      developed for the determination of the oxidation hair dyes 4-amino-m-cresol (4
      AC) and 5-amino-o-cresol (5-AC) and their metabolites in the alternative testing
      system human keratinocytes (HaCaT) cell culture. The culture medium induced by 3
      methylcholanthrene (3-MC) was fortified with 4-AC or 5-AC and incubated for 24 h
      at 37 degrees C in order to produce metabolites. After several pre-cleaning
      steps, further cleaning was done by solid-phase extraction using C18 phenyl
      cartridges. Optimizing chromatographic conditions, a hybrid-based RP8 column was
      most suitable for the separation of the metabolites formed in HaCaT. Only one
      conjugation product, the N-acetylated derivative, could be identified for both 4
      AC and 5-AC by LC/DAD/MS. The ionisation technique used for MS analysis was
      Atmospheric Pressure Ionization (API).

PMID- 15560920
TI  - Determination of 4-amino-m-cresol and 5-amino-o-cresol by high performance liquid
      chromatography and fluorescence derivatization using fluorescamine.
AB  - For the determination of two oxidation hair dyes, 4-amino-m-cresol (4-AC) and 5
      amino-o-cresol (5-AC), a sensitive isocratic high performance liquid
      chromatography (HPLC) method using the reversed phase mode was developed. The
      hair dyes were pre-column derivatized with fluorescamine prior to injection.
      Sensitivity could be improved 10-fold for 4-AC and 50-fold for 5-AC by
      fluorescence detection compared to UV detection. The limit of detection was 1
      ng/injection for 4-AC and 100 pg/injection for 5-AC, respectively. For the
      determination of both compounds in aqueous biological matrices in order to
      simulate conditions for penetration studies with pig skin, a solid phase
      extraction procedure using C18 cartridges and acetonitrile (ACN) for elution
      could be developed. Average recovery was 83.4% with a coefficient of variation
      (CV) of 2.64% for intra-day assay and 3.20% for inter-day assay for 5-AC and
      2.89% and 3.41% for 4-AC, respectively.

PMID- 15560921
TI  - HPLC-RIA analysis of steroid hormone profile in a virilizing stromal tumor of the
      ovary.
AB  - The pathological steroid biosynthesis of a virilizing ovarian tumor was examined
      via high performance liquid chromatography-radioimmunoassay (HPLC-RIA)
      determination of the intratissular steroid concentrations. Sex cord-stromal tumor
      of the ovary was obtained surgically from an 18-year-old female patient with
      extremely high androst-4-ene-3,17-dione (4-en-dione) and testosterone (Test)
      blood serum levels. The tissue specimen was extracted with ethyl acetate and the
      extract was then purified on a C18 mini-column with methanol-water eluents.
      Steroids were isolated by reversed-phase HPLC on a C18 silica gel column with
      51%, 55% and 64% v/v methanol-water eluents. Steroids in the collected eluent
      fractions were detected by the radioactivity of tritiated internal standards and
      then quantified by specific RIAs. In the tumor specimen, very high 17alpha
      hydroxyprogesterone (17-OH-Prog; 6300 fmol/g), dehydro-epiandrosterone (2870
      fmol/g), androst-4-ene-3,17-dione (3000 fmol/g), testosterone (5700 fmol/g)
      concentrations, and less progesterone (PROG; 320 fmol/g) and androst-5-ene
      3beta,17beta-diol (5-en-diol; 320 fmol/g), were determined. Tissue levels of
      5alpha-dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha
      diol), 5alpha-androstane-3beta,17beta-diol (3beta-diol), and 17beta-estradiol
      were found to be 71, 20, 28, and 12 fmol/g, respectively. Steroid profile
      analysis verified a pathological steroid biosynthesis in the ovarian tumor and
      suggested that the 17alpha-hydroxylase (17alpha-H), 17,20-lyase (17,20-L), and
      3beta-hydroxysteroid dehydrogenase/Delta5-4-isomerase (Delta5-3beta-HSD)
      activities were particularly elevated in this tumorous tissue. Present data
      demonstrate that the analysis of intratissular steroid profile by a HPLC-RIA
      method may valuably contribute to the steroidal pathophysiology of endocrine
      tumors.

PMID- 15560922
TI  - Determination of diffusion coefficient in gel and in aqueous solutions using
      scanning electrochemical microscopy.
AB  - Diffusion coefficient of different species in different media is an important
      property needed in scientific research and practice. A method taking advantage on
      the special capability of scanning electrochemical microscopy (SECM) is described
      for the easy and accurate measurement of diffusion coefficient. The method is
      based on detecting the concentration-time transients with appropriate
      electrochemical microsensor positioned at the close vicinity of a miniature dose
      source device. At a given time (ti), a small dose of the investigated species is
      introduced. The Deltatmax=(tcmax-ti) value and the distance (d=x+Deltaxn) between
      the source and the detector microelectrode are used for the calculation of D.
      While the original set distance (x) cannot be accurately measured in the
      micrometer scale, the tip travel distance (Deltaxn) of the microscope is well
      defined. Collecting a few Deltatmax-(x+Deltaxn) data pairs, a reliable value of
      the diffusion coefficient can be obtained. The procedure is simple, and no exact
      knowledge of the introduced dose is needed. Two ways of sample dose delivery were
      used: on the one hand, coulometric generation with current-controlled electric
      pulse using micro-disc electrode, and on the other one, pressure ejection of a
      nano-droplet from a glass micropipette. Diffusion coefficient of I2, H2O2,
      [Ru(NH3)6]Cl3 and K3[Fe(CN)6] were measured in solution and in agarose gel phases
      of different composition. The effect of polyelectrolyte ion exchangers on the
      diffusion of the investigated species was checked.

PMID- 15560923
TI  - Unexpected reactivity difference between iodo-alkene moieties of steroids
      possessing remote lactame or cycloalkane structural units: a theoretical
      approach.
AB  - The steroidal ring A possessing cyclohexane vs. delta-valerolactame structures
      shows a 'long-range effect' on the reactivity of the 'iodovinyl' functionality of
      the ring D. The strikingly different reactivity of 17-iodo-16-ene functionality
      of steroids is explained on the basis of the redistribution of kinetic energy of
      the system. The vibrational energy localized on the 'iodovinyl' moiety proved to
      be determinant in the CI bond-breaking process. The appearance of the lactame
      moiety in the ring A supports a redistribution of the kinetic energy on the
      molecule. As a result, a drastic decrease in C-I bond stretching has been
      obtained, which could diminish the C-I bond breaking, and therefore, results in
      decreased reactivity of the iodovinyl moiety in agreement with experimental
      findings.

PMID- 15560924
TI  - MS and NMR investigation of bioactive quinazolones.
AB  - To prepare effective PARP [poly(ADP)-ribose)polymerase-1] inhibitors, starting
      from 2-mercapto-4(3H)-quinazolone (1), several S-alkyl derivatives--2
      alkylsulfanyl-3H-quinazolin-4-ones (2-5, 7-9)--as well as an S-benzyl derivative
      (10) were prepared using a simple alkylation method. Some of them are known
      compounds. Their structure was studied thoroughly by MS and NMR methods.

PMID- 15560925
TI  - Chemometrical classification of pumpkin seed oils using UV-Vis, NIR and FTIR
      spectra.
AB  - The main outcome of this work is elaboration of classification models for edible
      oil samples representing the most widespread brands of Austrian pumpkin seed oil.
      A complete spectral characterisation of the pumpkin seed oil samples by UV-Vis,
      NIR and FTIR spectra was obtained together with their basic sensorial
      classification. Chemometrical processing of the measured data enabled the
      detection of the most important spectral features, which are crucial for
      categorising the oils into two or three classes according to their sensory
      quality evaluated by a panel of experts. The elaborated models thus make it
      possible to predict the category into which a hitherto unclassified oil sample
      belongs--considering classification into either two categories, containing oils
      with overall acceptable scores or oils that were not accepted, or three
      categories, involving oils fulfilling all quality criteria, oils with good scores
      and not accepted oils. This will perspectively facilitate the determination of
      chemical substances responsible for bad taste, odour and colour of the respective
      oil brands, as well as finding substances contributing to the excellent sensorial
      perception of some tested products.

PMID- 15560926
TI  - Analysis of vibrational spectra of some new E- and Z-4-arylidene-3
      isochromanones; Part 2. Isomers and conformers of the 2'-pyrrolyl and 2'
      nitrophenyl derivatives.
AB  - The infrared and Raman spectra of resolved E and Z isomers of some 4-arylidene-3
      isochromanone derivatives were analyzed with the aim of pointing out the
      differences in vibrational behavior of their coexisting stable conformers.
      Quantum mechanical (QM) density functional (DFT/B3LYP/6-31*) and normal
      coordinate calculations were carried out to establish the equilibrium structures
      and to facilitate the interpretation of the vibrational spectra of the 2'
      pyrrolyl and 2'-nitrophenyl derivatives. The frequencies and intensities
      calculated according to the scaled quantum mechanical (SQM) force field method
      were used to simulate the IR and Raman spectra and compare them to the measured
      ones. The results demonstrate that the adopted methodology is capable of treating
      these fairly large polycyclic molecules. The resulting spectral simulations and
      detailed vibrational description can be highly useful in clarifying spectral
      differences brought about by cis-trans isomerism and indicating the extent of
      spectral changes due to further conformational changes of the aryl substituent
      attached to the olefinic C=C bond.

PMID- 15560927
TI  - Determination of lipoic acid in dietary supplement preparations by capillary
      electrophoresis.
AB  - The present study deals with the development of a method for the quantitative
      determination of lipoic acid in a dietary supplement preparation. A rapid
      capillary electrophoretic method is developed using UV detection at 208 nm.
      Although lipoic acid is only weakly UV-absorbing, at this wavelength it could be
      detected with sufficient sensitivity with an LOD and LOQ of 0.8 and 2.5
      microg/ml, respectively. Analysis time was less than 9 min. The compound was
      extracted from tablets with a recovery of 98.3% and a precision of 2.8% RSD.

PMID- 15560928
TI  - Use of ultrabright LEDs for the determination of static and time-resolved
      florescence information of liquid and solid crude oil samples.
AB  - Ultrabright light emitting diodes (LEDs) are an inexpensive alternative to laser
      diodes (LDs) and other short wavelength emitting light sources. They have a high
      stability, a long lifetime, and a very low power consumption. A large number of
      publications are already available for fluorescence applications using this type
      of LEDs. Most of them are describing fluorescence intensity measurements. Only
      some of them are dealing with time-resolved methods, like single photon timing.
      LED modulation fluorometry is a very recent application, which can also be used
      for environmental investigations, like the detection of polycyclic aromatic
      hydrocarbons (PAHs). This article demonstrates the possible application of
      ultrabright LEDs for the time-resolved fluorescence detection of crude oil
      contaminated samples.

PMID- 15560929
TI  - Comparison of effect of selected synthetic chalcone analogues on mitochondrial
      outer membrane determined by fluorescence spectroscopy.
AB  - Effect on mitochondrial outer membrane of six selected synthetic cyclic chalcone
      analogues, E-2-arylmethylene-1-tetralones (2) and E-2-arylmethylene-1
      benzosuberones (3), were investigated by fluorescence spectroscopy. The selected
      compounds represent derivatives with different degree of cytotoxicity against
      murine and human cancer lines. Excitation and emission fluorescence spectra of
      the cyclic chalcone analogues 2 and 3 were recorded in respiration medium
      containing 1 mM succinate. It was found that the ring size as well as the nature
      and location of the aromatic substituents have significant effect on fluorescence
      of the compounds. Interaction of subtoxic concentration of compounds 2 and 3 with
      the outer mitochondrial membrane was investigated by recording their fluorescence
      polarization in the presence of rat liver mitochondria. The most cytotoxic E-2
      (4'-methoxybenzylidene)-1-benzosuberone (3b) was found to display a continuous
      increase of fluorescence polarization signal in the presence of mitochondria--a
      different pattern of interaction with the mitochondrial outer membrane from that
      observed for rest of the investigated compounds.

PMID- 15560930
TI  - Comparative study of turbulent solid-liquid extraction methods for the
      determination of organochlorine pesticides.
AB  - The aim of any extraction method in analytical chemistry is to effectively
      separate the analytes from the matrix with minimal solvent and time required. In
      this study, a comparison of the classical Soxhlet extraction and some new
      turbulent solid-liquid extraction techniques, such as fluidized-bed extraction
      (FBE), modified dive-in fluidized-bed extraction (dive-in FBE), modified dive-in
      Soxhlet extraction (dive-in SE) and dive-in thimble extraction (dive-in TE) for
      the determination of organochlorine pesticides (OCPs) was carried out. The
      turbulent extraction methods were performed by using the fexIKA vario control
      series extractor and by modification of the extraction system to dive-in
      technique, respectively. In addition, FBE and dive-in FBE were operated under the
      same, only for the FBE system established, optimum conditions. For the
      determination of the analytes a selective clean-up of the extracts followed by a
      gas chromatography (GC) method with mass spectrometric detection was used. All
      advanced extraction methods with reduced time and solvent consumption exhibited
      higher extraction efficiency than the standard procedure, Soxhlet extraction.

PMID- 15560931
TI  - Analysis of minor components in olive oil.
AB  - Virgin olive oil is well known for its high content of phenolic substances that
      are thought to have health-promoting properties. These substances also contribute
      to the distinctive taste of the oil. In this study, tyrosol, vanillic acid,
      luteolin, and apigenin were identified and quantified by liquid chromatography
      mass spectrometry (LC-MS). In the seven samples analysed, tyrosol, the most
      abundant, was in the range of 1.4-29 mg/kg, vanillic acid was in the range of
      0.67-4.0 mg/kg, luteolin was in the range of 0.22-7.0 mg/kg, and apigenin was in
      the range of 0.68-1.6 mg/kg. It was also shown that in olive oil, squalene can be
      analysed by using a refractive index detector. In the samples analysed, squalene
      occurred in the range of 3.9-9.6 g/l.

PMID- 15560932
TI  - Acrylamide in Austrian foods.
AB  - Acrylamide is known for its potential health hazards. Recently acrylamide was
      found in starch containing heated foods in high concentrations which lead to the
      assumption that a cancer risk could be associated with the uptake of foods
      containing high amounts of acrylamide. This study focuses on the analysis of
      acrylamide in foods potentially containing this substance which is formed from
      natural ingredients. The highest concentrations were found in potato crisps with
      concentrations of above 1500 ng/g (median: 499 ng/g). Other food groups contained
      lower amounts: cookies with a median of 99 ng/g; crisp bread with a median of 69
      ng/g; breakfast cereals with a median of 0 ng/g; popcorn and rice products with a
      median of 97 ng/g; potato chips with a median of 161 ng/g and coffee with a
      median of 169 ng/g.

PMID- 15560933
TI  - Influence of several Styrian wines on bovine coronary artery contractions induced
      by endogenous agents.
AB  - In the current study, seven Styrian white wine varieties, as well as their
      corresponding grape skin extracts (GSE), were tested for possible antagonistic
      effects on several endogenous vasoconstrictors known to be involved in the
      pathogenesis of cardiovascular diseases via tissue contraction experiments.
      Results were compared to those of Zweigelt, the most cultivated Styrian red wine.
      Bovine coronary artery strips were attached to a force transducer connected to a
      bridge amplifier, and isometric force was recorded on a multipen recorder.
      Preincubation of the vessels with the dealcoholized wines (DAW; 330 microl/ml)
      inhibited the constrictions to histamine and serotonin (5-HT) NO-dependently in
      the range of 5-80% and 30-90%, respectively (Zweigelt 47% and 90%, respectively).
      The corresponding GSE (20 mg/ml) inhibited the coronary constrictions to
      histamine in the range of 40% to 80% (Zweigelt 80%). Additionally, all DAW
      antagonized the contractile responses to the thromboxane-mimetic U46619 and the
      isoprostane 8-iso-PGF2alpha, indicating a nonspecific inhibition. To characterize
      the vasoactive component(s), the Traminer GSE was separated representatively
      using ultrafiltration, solid phase extraction (SPE) on Isolute C18(EC), and
      Isolute SCX-2, as well as column chromatography (CC) on polyamide. The resulting
      fractions were subsequently bioassayed for vasorelaxing activity. Preliminary
      results refer to a very hydrophilic, nonpolyphenolic basic compound with a
      MW<1000 Da. Our findings demonstrate that certain Styrian wines have remarkable
      antagonistic effects on several endogenous agonists in vitro, and that also
      nonpolyphenolic components in grapes may contribute to cardiovascular protection.
      Further separation steps as well as phytochemical and pharmacological
      investigations are in progress.

PMID- 15560934
TI  - Laser Scanning Cytometry for selection of green fluorescent protein transgenic
      mice using small number of blood cells.
AB  - A Laser Scanning Cytometry-based method was developed for identification of
      transgenic mice expressing green fluorescent protein (GFP) using minute amounts
      of peripheral blood. The difference between the autofluorescence of cells not
      expressing GFP and the fluorescence of GFP expressing cells after excitation with
      Ar-ion laser (wavelength 488 nm) and detection of emitted fluorescent light in
      the green channel was high enough for unambiguous identification of the GFP
      expressing mice. The sensitivity of this method was estimated 1:10(4) for
      detection of rare GFP expressing cells under the conditions used. This
      sensitivity should be sufficient for many studies on microchimerism. Because of
      the possibility for relocation of the cells, this method will be particularly
      useful for characterizing the cells with high GFP expression using other markers
      of cell phenotype or conventional morphological analysis.

PMID- 15560935
TI  - Distribution of PACAP-38 in the central nervous system of various species
      determined by a novel radioimmunoassay.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) occurs in two
      molecular forms: PACAP-38 and PACAP-27. Soon after the isolation and chemical
      characterization of PACAP, the first radioimmunoassay (RIA) methods have been
      developed, but it is a still rarely used laboratory technique in the field of
      PACAP research. The aim of the present study was to develop a novel, highly
      specific PACAP-38 assay to investigate the quantitative distribution of PACAP-38
      in the central nervous system of various vertebrate species under the same
      technical and experimental conditions. Different areas of the brain and the
      spinal cord were removed from rats, chickens and fishes and the tissue samples
      were processed for PACAP-38 RIA. Our results indicate that the antiserum used in
      the RIA is C-terminal specific, without affinity for other members of the
      vasoactive intestinal polypeptide (VIP)/secretin/glucagon peptide family. The
      average ID50 value was 48.6+/-3.4 fmol/ml determined in 10 consecutive assays.
      Detection limit for PACAP-38 proved to be 2 fmol/ml. PACAP-38 immunoreactivity
      was present in the examined brain areas of each species studied, with highest
      concentration in the rat diencephalons. High levels of PACAP-38 were also
      detected in the rat telencephalon, followed by spinal cord and brainstem. The
      central nervous system of the fish also contained considerable concentrations of
      PACAP-38, whereas lowest concentrations were measured in the central nervous
      system of the chicken.

PMID- 15560936
TI  - Urinary steroids in young women with eating disorders.
AB  - Urinary steroid components were measured after enzyme hydrolysis and methoxym
      silyl derivatization by capillary gas chromatography in young women with eating
      disorders. Using three internal standards, programmed temperature from 50 to 300
      degrees C and flame ionization detection, on ULTRA-1 capillary column the
      separation of 28 steroid components is possible. Fifteen young women with
      different eating disorders, i.e. anorexia nervosa, bulimia nervosa and
      bulimarexia (aged 16-28 years) and 15 healthy women (aged 22-26 years) collected
      24-h urine. A significant decrease of dehydroepiandrosterone (p<0.05) and a
      significant elevation of the stress marker allo-tetrahydrocorticosterone (p<0.05)
      were observed in the patients with compared to the controls. Among the patients
      two groups were defined due to a significant difference in the content of the
      cortisol metabolites compared to each other and to controls (p<0.01). The results
      confirm the role of dehydroepiandrosterone in eating disorders. The increased
      level of the stress marker allo-tetrahydrocorticosterone refers to the
      involvement of stress in these diseases, but the relevance of hormone alteration
      to the pathophysiology of eating disorders remains to be elucidated. The reason
      of the differences in cortisol metabolites levels in some patients needs further
      investigations.

PMID- 15560937
TI  - Thermal analysis of the human intervertebral disc.
AB  - Intervertebral disc (IVD) degeneration is one of the most common musculuskeletal
      disorders affecting western society. Degeneration alters the morphology and the
      mechanical properties of the discs. According to previous reports, DSC proved to
      be a suitable method for the demonstration of thermal consequences of local as
      well as global conformational changes in the structure of the human
      intervertebral discs. In the present study, a wide spectrum of degenerated IVD
      was examined by DSC. The results suggest that definitive differences exist
      between the stages of disc degeneration in calorimetric measures.

PMID- 15560938
TI  - Earthworm leukocytes kill HeLa, HEp-2, PC-12 and PA317 cells in vitro.
AB  - Earthworm coelomic fluid contains biologically active molecules and leukocytes
      that participate in phagocytosis, encapsulation. Presumably they synthesize and
      secrete several effector modulators of innate immune responses such as
      antibacterial molecules, cytotoxic proteins and cytokines. Several lytic
      molecules have been detected in coelomic fluid previously but it is not yet clear
      which are actually released from the coelomocytes. Our aim was to analyze the
      cytotoxic effects of coelomocytes on mammalian target cells and to provide
      evidence that the lytic factors originate from coelomocytes. Cell-free coelomic
      fluid, supernatants of short-term cultured coelomocytes, and lysates from
      coelomocytes--derived by mechanical and detergent extraction--were used in
      cytotoxicity assays performed on different mammalian standard tumor cell lines
      and mouse fibroblasts. We used native and denaturized (using proteinase K, and
      trypsin digestions, or heat-inactivation) coelomocyte lysates (CCL). The
      viability controls of targeted cells were made by measuring photometrically and
      analyzing by inverted microscopy. According to our results the coelomic fluid,
      the supernatant of cultured coelomocytes, and the CCL significantly decreased
      ratios of living cells compared to controls in a dose-dependent manner. Our
      experiments performed with CCLs suggest that coelomocytes are responsible for the
      productions of cytotoxic components presumably proteins.

PMID- 15560939
TI  - Sodium salicylate inhibits NF-kappaB and induces apoptosis in PC12 cells.
AB  - Sodium salicylate (NaSal) is an effective analgetic and antiinflammatory drug.
      Beside its well-known inhibitory effect on the cyclooxigenase enzymes, it
      influences the activity of other signal transduction proteins including nuclear
      factor kappa B (NF-kappaB) transcription factor. NF-kappaB is found in the
      cytoplasm bound to an inhibitory protein, inhibitory kappa B (IkappaB). After its
      phosphorylation, IkappaB is degraded and the released NF-kappaB translocates into
      the nucleus. Sodium salicylate inhibits the degradation of IkappaB, thus, NF
      kappaB activation cannot occur. According to previous observations, the
      inhibition of this activation can lead to apoptosis. The main goals of this study
      were to demonstrate that inhibition of NF-kappaB by sodium salicylate decreases
      the viability of rat phaeochromocytoma PC12 cells and to investigate the nature
      of cell damage and death. PC12 cells were treated with different concentrations
      of sodium salicylate (1-20 mM). Higher concentrations (10-20 mM) killed PC12
      cells in a dose-dependent manner. The assessments were done by direct cell
      counting in a Burker chamber and by the WST-1 cytotoxicity assay. We also found a
      decreased NF-kappaB activity after sodium salicylate treatment by electrophoretic
      mobility shift assay (EMSA). The cells treated with sodium salicylate were
      undergoing apoptosis as seen on our records obtained by time-lapse
      videomicroscopy as well as shown by DNA fragmentation experiments. The decreased
      DNA binding activity of NF-kappaB indicates that the inhibition of NF-kappaB can
      play a role in these processes.

PMID- 15560940
TI  - Mass spectrometric studies on the coupling model reaction towards alkenyl-aryl
      ketones.
AB  - The palladium catalysed coupling reactions of 1-iodo-cyclohexene have been
      investigated with the aim of the synthesis of model compounds towards unsaturated
      aryl-alkenyl ketones of practical interest in carbonylative Suzuki reaction. In
      addition to the target compounds, the formation of 1-aryl-cyclohexene
      derivatives, 1,1'-bi(cyclohex-1-en-1-yl), 1,2-dicyclohex-1-en-1-yl-ethane-1,2
      dione, dicyclohex-1-en-1-yl-ketone and 1-aryl-2-cyclohexenyl-cyclohexene
      derivatives, as well as their isomerization products, have been observed in
      parallel and consecutive reactions, respectively. The complex reaction mixtures
      have been analysed with GC-MS providing valuable information to the investigation
      of the homogeneous catalytic reaction.

PMID- 15560941
TI  - Assessing problems of organic hydroperoxide-induced chemiluminescence related to
      biological/medical samples.
AB  - The supernatants obtained from mammalian tissue homogenates, blood serum or other
      body fluids, and supplemented with organic hydroperoxide show a multiplicity of
      light-emitting reactions. The low-level chemiluminescence of biological samples
      denotes that after hydroperoxide-induction electronically excited species are
      produced. The light-emission measured by photomultipliers is related to (i) the
      geometrical location of the induced sample, (ii) light gathering capacity of the
      phototubes, and (iii) both the quantity and concentration of samples and
      reactants. The fewest blood contamination of biological samples leads to an
      increased photoemission. The very high sensitivity of light detectors requires
      stable measuring and sampling conditions and peculiarly cautious evaluation of
      the reactions.

PMID- 15560942
TI  - Pre-clinical methods for the determination of insulin sensitivity.
AB  - We compared the hyperinsulinaemic euglycaemic glucose clamping (HEGC) procedure
      and the rapid insulin sensitivity test (RIST) to characterize insulin sensitivity
      in anaesthetized rats. The changes in insulin sensitivity were then supplemented
      with the direct measurement of insulin-stimulated glucose uptake using tissue
      accumulation of radioactive 2-deoxyglucose in skeletal muscle samples obtained
      from animals undergone either procedure. Studies of the recently described
      endogenous insulin sensitizer mechanism termed hepatic insulin sensitizing (HISS)
      mechanism, by the two methods yielded data for evaluation. The HISS mechanism is
      defined as an increase in tissue insulin sensitivity in response to post-prandial
      hepatic release of an undefined substance through a nitrergic pathway. For the
      HEGC method, insulin was infused to attain a stable plasma insulin
      immunoreactivity of 100 microU/ml determined by radioimmunoassay, whereas with
      the RIST method the HISS mechanism was activated by a 50 mg/kg i.v. insulin
      bolus. Euglycaemia was kept constant by means of glucose infusion. With the HEGC
      and the RIST methods, insulin sensitivity was defined as the average rate of
      glucose infusion and the amount of glucose/kg body weight/40 min (RIST index)
      infused to maintain euglycaemia and preinvestigation blood glucose level,
      respectively. During HEGC 16+/-4.2 mg/kg/min glucose was able to maintain
      euglycaemia, which decreased to 8+/-2.9 (p<0.05) after administration of 10 mg/kg
      NG-nitro-L-arginine methyl ester (L-NAME) (i.p.), a NO synthase inhibitor.
      Conversely, the RIST index decreased by 55+/-6.9% (p<0.05) after L-NAME.
      Similarly, 2-deoxyglucose uptake by the gastrocnemius muscle was decreased by
      49.9+/-5.8 (p<0.05) and 52.3+/-7.4% (p<0.05) with the HEGC and the RIST methods,
      respectively. The results show that both the HEGC and the RIST methods
      supplemented with tissue radioactive 2-deoxyglucose uptake determinations are
      appropriate methods to characterize the alteration of insulin sensitivity in
      context of the HISS mechanism.

PMID- 15560943
TI  - Trends in particulate antigen and DNA delivery systems for vaccines.

PMID- 15560944
TI  - Need for new vaccine formulations and potential of particulate antigen and DNA
      delivery systems.

PMID- 15560945
TI  - Immunity in response to particulate antigen-delivery systems.
AB  - Adjuvants and antigen-delivery systems are essential in inducing and modifying
      immune responses, and despite the variety of materials available for such use,
      mechanisms by which they support immunity appear to be little known. A common
      denominator for most antigen-delivery systems is their particulate nature.
      Together with a certain depot effect, it is the particulate nature that primarily
      decides whether the antigen-delivery system will be successful in inducing an
      immune response. If this first requirement is fulfilled, the chemical composition
      of the vaccine decides which type of immune response will develop, e.g. which
      isotype of antibodies the B cells will produce, and which cytokines the T cells
      will secrete, and can be controlled by combining the antigen with
      immunomodulatory or co-stimulatory molecules. It is our goal to provide an
      overview of the cellular and molecular factors involved in the induction of
      immunity and how such factors may influence the potency of an adjuvant or a
      vaccine. Such factors should then be implemented in the design of new vaccines or
      in tuning the properties of existing vaccines in order to reach the properties
      that are necessary for successful vaccination.

PMID- 15560946
TI  - Formulation aspects of biodegradable polymeric microspheres for antigen delivery.
AB  - Biodegradable microspheres (MS) have proven to be very useful antigen delivery
      systems that are ingested by immunocompetent cells and provide prolonged antigen
      release and lasting immunity thanks to sustained release of the microencapsulated
      material. This review provides an applicable summary of different formulation
      routes for the purpose of producing safe, qualified and efficacious products of
      microencapsulated peptide and protein antigens. We have brought to attention,
      with case examples, not only the most common means of improving the quality of
      microsphere formulations, i.e., the use of stabilising additives, but also less
      commonly known and applied approaches, e.g., ion pairing, novel polymer systems,
      solid-state and other innovative microencapsulation methods.

PMID- 15560947
TI  - DNA-loaded biodegradable microparticles as vaccine delivery systems and their
      interaction with dendritic cells.
AB  - This paper provides a review of the role of dendritic cells (DC) in microparticle
      mediated immune response and the advantages of associating DNA to microparticles
      in order to increase the potency of DNA vaccination in vivo. To begin with,
      different methods for the preparation of DNA-loaded microparticle with
      poly(lactide) (PLA)/poly(lactide-co-glycolide) (PLGA) polymers are presented.
      Further, the effects of DNA-loaded microparticles on DC in vitro are extensively
      examined including transfection and stimulation of DC, a key feature of the
      immune response. Finally, in vivo tracking of DNA-loaded microparticles and
      induction of immune responses upon DNA-loaded microparticle administration in
      different animal models and with various routes of administration are reviewed.

PMID- 15560948
TI  - Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable
      delivery of vaccine antigens.
AB  - Injectable biodegradable polymeric particles (usually microspheres) represent an
      exciting approach to control the release of vaccine antigens to reduce the number
      of doses in the immunization schedule and optimize the desired immune response
      via selective targeting of antigen to antigen presenting cells. After the first
      couple of decades of their study, much progress has been made towards the
      clinical use of antigen-loaded microspheres. Poly(lactide-co-glycolic acids)
      (PLGAs) have been studied most commonly for this purpose because of their proven
      safety record and established use in marketed products for controlled delivery of
      several peptide drugs. PLGA microspheres have many desirable features relative to
      standard aluminum-based adjuvants, including the microspheres' ability to induce
      cell-mediated immunity, a necessary requirement for emergent vaccines against HIV
      and cancer. This review examines several impediments to PLGA microparticle
      development, such as PLGA-encapsulated antigen instability and deficiency of
      animal models in predicting human response, and describes new trends in
      overcoming these important issues. PLGA microparticles have displayed
      unprecedented versatility and safety to accomplish release of one or multiple
      antigens of varying physical-chemical characteristics and immunologic
      requirements, and have now met numerous critical benchmarks in development of
      long-lasting immunity after a single injected dose.

PMID- 15560949
TI  - Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA
      delivery.
AB  - Biodegradable polymer and particulate carriers have been shown to be of
      considerable potential for the delivery of peptides, proteins and DNA in animal
      models. In the context of vaccine delivery to the upper and lower respiratory
      tracts, the use of mucoadhesive agents offers a strategy for the facilitation of
      increased residence time and increased vaccine efficacy. Additional concerns
      addressed here include the potential of uptake of vaccine formulations by the
      primary olfactory nerves in the nasal cavity, effective delivery to the lung,
      strategies to maximise the immunopotentiation of candidate vaccine formulations,
      as well as the evaluation of animal models and interpretation of engendered
      immune responses in terms of antigen-specific antibody production. Experimental
      data are presented that demonstrate the potential of muco- and bioadhesive agents
      in combination with liposomes for intranasal (i.n.) delivery of tetanus toxoid in
      mice. A delivery system utilising chitosan for the formulation of microspheres by
      the spray-drying method is described and assessed for intranasal vaccine
      delivery, and porous particles with potential for pulmonary administration are
      also outlined.

PMID- 15560950
TI  - Exploiting receptor biology for oral vaccination with biodegradable particulates.
AB  - The effective delivery of antigens via the oral route is an extremely desirable
      goal. Mucosal delivery of antigens stimulates mucosal and systemic immunity
      without affecting maternal antibodies and reduces the need for sterile needles or
      trained personnel. To date, there are very few commercially available oral
      vaccines and despite numerous reports in the scientific literature to show the
      success of biodegradable antigen carriers, none of these have achieved commercial
      status. Nevertheless, many studies have shown the great potential of
      biodegradable antigen carriers for oral vaccination in preclinical studies, but a
      more rational approach may be to specifically target antigen-loaded biodegradable
      microspheres to cells in the mucosal immune system which transport and process
      antigens for T cell recognition. Modern cell and molecular biology techniques
      have unearthed a wealth of information regarding important receptors involved in
      the capture of luminal antigens by microfold or membranous (M) cells and
      receptors on dendritic cells (DCs) which may allow future targeting of antigens
      to specific DC phenotypes, thus directing the immune response appropriately. In
      this review, we consider the use of currently available biodegradable antigen
      carriers and speculate on how these may be improved to more efficiently target
      mucosal effector sites.

PMID- 15560951
TI  - Virosomes for antigen and DNA delivery.
AB  - Specific targeting and delivery as well as the display of antigens on the surface
      of professional antigen-presenting cells (APCs) are key issues in the design and
      development of new-generation vaccines aimed at the induction of both humoral and
      cell-mediated immunity. Prophylactic vaccination against infectious diseases in
      general aims at the induction of humoral immune responses to prevent infection.
      This humoral immune response is mediated by antibody-producing B cells. On the
      other hand, therapeutic immunisation against virally infected cells and tumour
      cells requires the induction of cytotoxic T lymphocytes (CTLs) that can
      specifically recognise and lyse infected cells or transformed tumour cells. The
      induction of Major Histocompatibility Complex (MHC) class I restricted CTL
      activity is optimally achieved by synthesis of antigens within APCs, for example,
      after immunisation with live attenuated virus. However, immunisation with live
      vaccines bears the risk of causing disease. Therefore, alternative vaccine
      delivery systems, which enable introduction of nonreplicating antigen into the
      MHC class I presentation pathway, are sought. Furthermore, for the induction of
      effective humoral and cellular responses, MHC class II restricted activation of T
      helper cells (Th cells) is required. Among other delivery systems, as described
      in this theme issue of Advanced Drug Delivery Reviews, virosomes seem ideally
      suited for delivery of antigens into both MHC pathways. In this review, we will
      focus on the use of virosomes as carrier vehicles for the intracellular delivery
      of protein antigens and DNA, and the induction of a cellular immune response
      against encapsulated protein antigens and proteins expressed by virosome
      associated plasmids.

PMID- 15560952
TI  - ISCOMATRIX adjuvant for antigen delivery.
AB  - The immunostimulating complex, referred to as 'iscom', was first described by
      Morein et al. in 1984 as a novel structure for antigenic presentation of membrane
      proteins from enveloped viruses with potent immunomodulatory capability . Since
      this discovery, many vaccines have been tested in animal models showing the
      induction of both humoral and cellular immune responses . The ISCOMATRIX adjuvant
      is essentially the same structure as the iscom but without the incorporated
      antigen . Antigens can be formulated with the ISCOMATRIX adjuvant to produce
      ISCOMATRIX vaccines that can provide the same antigen presentation and
      immunomodulatory properties as the iscom but with much broader application as
      they are not limited to hydrophobic membrane proteins. Various ISCOMATRIX
      vaccines have been tested in animal models and more recently in human clinical
      trials . These studies have shown that the ISCOMATRIX adjuvant is safe and
      induces both humoral and cellular immune responses. The ability of the ISCOMATRIX
      adjuvant to induce these broad immune responses is due to the combination of
      antigen presentation by both MHC class I and class II pathways, and the powerful
      immunomodulatory capability of the saponin. Additionally, the ISCOMATRIX adjuvant
      is simple to manufacture and can be combined with a wide range of antigens making
      it suitable for the development of novel human vaccines.

PMID- 15560953
TI  - PLGA microspheres for improved antigen delivery to dendritic cells as cellular
      vaccines.
AB  - Dendritic cells (DC) are currently employed as cellular vaccines in clinical
      trials of tumor immunotherapy. In most trials, peptide epitopes derived from
      tumor antigens are being exogenously loaded onto human DC for binding to MHC
      class I molecules. While this is a convenient method, it suffers from the
      drawback that the persistence of class I/peptide complexes on the cell surface is
      in the order of a few hours. This drawback limits the success of vaccination. We
      have investigated biodegradable poly(D,L-lactide-co-glycolide) microspheres (PLGA
      MS) as delivery tools for antigen loading of human monocyte-derived DC (hMoDC).
      Immature hMoDC readily take up PLGA-MS and present epitopes from encapsulated
      proteins or peptides both on MHC class I and class II. Interestingly, antigen
      presentation by hMoDC was markedly prolonged when hMoDC were charged with PLGA-MS
      encapsulated as opposed to soluble antigens. The properties of hMoDC with respect
      to migration, cytokine secretion, survival and allostimulation were not adversely
      affected by the uptake of PLGA-MS. In this article, we will review the properties
      of PLGA-MS as an adjuvant and summarize recent data on their potential for
      antigen delivery to dendritic cells.

PMID- 15560954
TI  - Schizophrenia, epigenetics and ligand-activated nuclear receptors: a framework
      for chromatin therapeutics.
AB  - Covalent modifications of DNA and its surrounding chromatin constitute an
      essential and powerful regulatory mechanism for gene transcription. Epigenetics
      is the study of this regulatory system. There is now strong albeit indirect
      evidence that epigenetic mechanisms contribute to the pathophysiology of
      schizophrenia. Furthermore, the discovery that valproic acid, a widely used
      psychotropic, has powerful epigenetic effects in clinically relevant
      concentrations suggests new therapeutic possibilities, i.e., drugs that act on
      chromatin structure. Fortunately, many proteins engaged in these processes,
      particularly chromatin remodeling, are accessible to pharmacological agents that
      have a high likelihood of crossing the blood brain barrier. This review will
      first summarize the essentials of the epigenetic regulatory system, then address
      the molecular evidence for altered epigenetic mechanisms in schizophrenia, and
      finally focus on the retinoic acid family of ligand-activated nuclear
      transcription factors as a likely system for new drug development in the
      management of schizophrenia-related symptoms.

PMID- 15560955
TI  - Volume of the cingulate and outcome in schizophrenia.
AB  - BACKGROUND: Previous studies indicated that schizophrenia patients have reduced
      frontal volumes in comparison with normal, but among schizophrenics, reduced
      volumes of the posterior (temporal, parietal and occipital) cortex were
      associated with poor outcome. We examined whether this pattern is seen within the
      anteroposterior arch of the cingulate gyrus. METHODS: MR images were acquired in
      37 schizophrenia patients (Kraepelinian, n = 13; non-Kraepelinian, n = 24) and 37
      controls, and CSF, gray and white matter volumes in individual Brodmann's areas
      (BA) of the cingulate arch (areas 25, 24, 23, 31, 30, 29) were assessed and
      examined in relation to outcome. RESULTS: Schizophrenia patients had significant
      gray matter reductions in the absolute (mm(3)) volume of Brodmann's area 24 in
      anterior cingulate and, when corrected for brain size, in the whole cingulate and
      retrosplenial (areas 29-30) cortex. White matter volumes were increased in right
      posterior cingulate (area 31). Schizophrenia patients also showed abnormal
      lateralization of white matter volumes in retrosplenial cortex (area 30) and had
      lower correlations between frontal and anterior cingulate regions than controls.
      Poor-outcome subgroup exhibited significant bilateral gray matter deficits in
      posterior cingulate and retrosplenial cortices compared to good-outcome patients,
      while no white matter increases in these areas were seen. CONCLUSIONS: Poor
      outcome was associated with gray matter deficits in posterior cingulate while
      compensatory white matter increases in dorsal posterior regions may be related to
      better outcome. Possible consequences of this may include thought disorder,
      disturbance of consciousness, treatment resistance, and cognitive decline
      indicative of a dementing process as a superimposed or inherent part of this
      schizophrenia subtype.

PMID- 15560956
TI  - GABAergic dysfunction in schizophrenia and mood disorders as reflected by
      decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins
      in cerebellum.
AB  - BACKGROUND: Glutamic acid decarboxylase (GAD) is the rate limiting enzyme
      responsible for conversion of glutamate to gamma-aminobutyric acid (GABA)
      regulating levels of glutamate and GABA in the mammalian brain. Reelin is an
      extracellular matrix protein that helps in normal lamination of the embryonic
      brain and subserves synaptic plasticity in adult brain. Both GAD and Reelin are
      colocalized to the same GABAergic interneurons in several brain sites. We
      hypothesized that levels of GAD and Reelin would be altered in cerebellum of
      subjects with schizophrenia and mood disorders differentially vs. controls.
      METHODS: We employed SDS-PAGE and Western blotting to measure levels of GAD
      isomers 65 and 67 kDa and Reelin isoforms 410-, 330- and 180-kDa proteins as well
      as beta-actin in cerebellum of subjects with schizophrenia, bipolar disorder and
      major depression vs. controls (N = 15 per group). RESULTS: GAD 65- and 67-kDa
      levels were decreased significantly in bipolar, depressed and schizophrenic
      subjects (p < 0.05) vs. controls. Reelin 410- and 180-kDa proteins decreased
      significantly (p < 0.05) in bipolar subjects vs. controls. Reelin 180 kDa was
      decreased significantly (p < 0.05) in schizophrenics vs. controls. beta-Actin
      levels did not vary significantly between groups. There were no significant
      effects of confounding variables on levels of various proteins. CONCLUSION: This
      study demonstrates for the first time significant deficits in GABAergic markers
      Reelin and GAD 65 and 67 proteins in bipolar subjects and global deficits in the
      latter proteins in schizophrenia and mood disorders, accounting for the reported
      alterations in CSF/plasma levels of glutamate and GABA in these disorders.

PMID- 15560957
TI  - A forced five-dimensional factor analysis and concurrent validity of the Positive
      and Negative Syndrome Scale in Mexican schizophrenic patients.
AB  - The heterogeneity of schizophrenic symptomatology is well documented. The
      positive-negative distinction is limited to cover the entire spectrum of
      schizophrenic psychopathology in order to describe the various clinical aspects
      of the disorder. METHOD: We recruited 150 schizophrenic patients between May 2002
      and September 2003. Diagnoses were based on a structured clinical interview. The
      Positive and Negative Syndrome Scale (PANSS) was used to evaluate general
      psychopathology and symptom severity. For the concurrent validity of the
      pentagonal model of the PANSS, the BPRS, the CDSS, the OAS and the MMSE were
      used. RESULTS: The forced five-factor principal-component analysis explained
      53.4% of the total variance. There were significant correlations between the
      clinical rating scales and the five components of the PANSS. DISCUSSION: Our data
      support a pentagonal model underlying the multidimensional schizophrenic
      symptomatology as assessed by the PANSS. The five-factor structure of the PANSS
      in Mexican schizophrenic patients enables further elucidation of the various
      clinical aspects of schizophrenia.

PMID- 15560958
TI  - Plasma clozapine concentration coefficients of variation in a long-term study.
AB  - Kurz et al. conducted the first study of the intra-individual variability of
      clozapine plasma concentrations but did not take into account the effect of
      smoking and co-medication. As patients were receiving varying doses, Kurz et al.
      standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients,
      the mean coefficient of variation (CV) was 53% (S.D. = 21). In this new study,
      plasma clozapine and norclozapine concentrations were measured every 2 weeks in
      47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind
      clozapine trials under controlled conditions (stable smoking, limited co
      medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day,
      the respective mean CVs for plasma clozapine concentrations were 23% (S.D. = 14),
      19% (S.D.= 11) and 18% (S.D. = 8). For the combined concentrations of clozapine
      and norclozapine, the respective mean CVs were 20% (S.D. = 13), 16% (S.D. = 9)
      and 15% (S.D. = 7). Under 100 mg/day, the mean CV for clozapine concentrations
      was significantly higher for heavy smokers than non-heavy smokers (32%, S.D. = 3
      vs. 19%, S.D. = 8) (p = 0.03). Studies of CVs in other environments are needed.
      Clozapine CVs may be important in order to understand the importance of
      variations around the therapeutic range and to interpret drug interactions above
      the usual noise of measuring plasma concentrations.

PMID- 15560959
TI  - Thinking within the spectrum: schizophrenic thought disorder in six Danish
      pedigrees.
AB  - Formal thought disorder (FTD), a major symptom of schizophrenia, is known to
      aggregate in families. Our aim was to examine the specificity of FTD in the
      schizophrenia spectrum disorders and the hypothesized linear aggregation of FTD
      within pedigrees. Six individuals with a diagnosis of schizophrenia were
      identified in the Copenhagen High-Risk study and each pedigree was centered on
      one of the six original schizophrenic probands' nuclear families. The 329
      pedigree members in the study were considered at risk for schizophrenia spectrum
      disorders because most were genetically related to the originating schizophrenic
      probands. The participants were administered the Copenhagen Interview of
      Functional Illness to determine diagnoses and the Thought Disorder Index (TDI)
      was used to assess FTD. Individuals with a schizophrenia diagnosis had higher
      global levels of FTD, exhibited more severe types of FTD, and had a qualitatively
      different type of FTD than did participants with other diagnoses or no mental
      illness. Individuals with Cluster A diagnoses exhibited more FTD and FTD similar
      in quality to participants with schizophrenia. These results support the
      construct of a spectrum of schizophrenia conditions. There was a generally high
      level of FTD in the pedigrees, in part due to assortative mating in this sample.
      However, there was no apparent pattern of linear aggregation of FTD within the
      families.

PMID- 15560960
TI  - Childhood laterality and adult schizophrenia spectrum disorders: a prospective
      investigation.
AB  - Left or mixed-handedness, footedness, and eye dominance are thought to indicate
      abnormalities in lateralization related to schizophrenia. Increased left or mixed
      dominance in schizophrenia suggests possible hemispheric abnormalities associated
      with the disorder. A related body of research suggests that some indications of
      lateralization abnormalities may be evident prior to the onset of schizophrenia,
      suggesting that disruptions in lateralization are inherent to the developmental
      course of the disorder. We attempted to replicate and extend upon findings
      indicating differences in lateralization between children who later developed a
      schizophrenia spectrum disorder (n = 26) and those who did not develop a
      schizophrenia spectrum disorder (n = 216), among a high-risk and control,
      longitudinal sample. The rate of left or mixed-footedness, eye dominance, and any
      anomalous lateralization, but not handedness, discriminated between those who
      developed schizophrenia spectrum disorders and those who did not. Left or mixed
      laterality appears to signal neurological disruption relevant to the development
      of schizophrenia spectrum disorders.

PMID- 15560961
TI  - Incidence and clinical correlates of aggression and violence at presentation in
      patients with first episode psychosis.
AB  - This study aimed to identify the incidence and clinical correlates of aggression
      and violence in first episode psychosis. We prospectively recruited subjects with
      a first episode of DSM-psychosis presenting from a geographically defined
      catchment area to a secondary referral psychiatric service over a four-year
      period (n = 157). We used the Modified Overt Aggression Scale to retrospectively
      assess aggression (a hostile or destructive mental attitude, including verbal
      aggression, physical aggression and/or violence) and violence (the exercise of
      physical force), blind to diagnosis. One in three patients with psychosis was
      aggressive at the time of presentation. One patient in 14 engaged in violence
      that caused, or was likely to cause, injury to other people. Aggression was
      independently associated with drug misuse (odds ratio (OR) 2.80, 95% confidence
      interval 1.12-6.99) and involuntary admission status (OR = 3.62, 95% CI 1.45
      9.01). Violence in the week prior to presentation was associated with drug misuse
      (OR = 2.75, CI 1.04-7.24) and involuntary admission status (OR = 3.21, CI 1.21
      8.50). Violence in the week following presentation was associated with poor
      insight (OR 2.97, CI 1.03-8.56) and pre-contact violence (OR 3,82, CI 1.34
      10.88). In patients with schizophrenia, violence in the week following
      presentation was associated with drug misuse (OR = 7.81, CI 1.33-45.95) and high
      psychopathology scores (OR = 20.59, CI 1.66-254.96). Overall, despite a high rate
      of verbal aggression, physical violence towards other people is uncommon in
      individuals presenting with first episode psychosis.

PMID- 15560962
TI  - Intact visual latent inhibition in schizophrenia patients in a within-subject
      paradigm.
AB  - People are normally slower to learn a CS-UCS association if they first experience
      the CS without the UCS. This normal slowing, termed "latent inhibition" (LI), is
      reported by some to be absent in schizophrenia patients. Our previous studies
      detected generalized learning deficits but not LI deficits in schizophrenia
      patients, using between-subject auditory and visual LI paradigms. To understand
      our divergent results, we developed a within-subject visual LI paradigm that
      detects LI in normal male subjects that we previously reported to be disrupted by
      acute treatment with dopamine agonists. In the present study, we verified the
      ability of this dopamine-sensitive within-subject LI paradigm to detect LI among
      both male and female normal control subjects, and then used this paradigm to
      assess LI in schizophrenia patients. Among normals, LI exhibited no sex
      differences or menstrual cyclicity. Compared to normals, schizophrenia patients
      exhibited learning deficits with both preexposed (PE) and non-preexposed (NPE)
      stimuli. Despite these generalized deficits, both acutely hospitalized patients
      and stable outpatients with schizophrenia exhibited robust LI, as evidenced by
      significantly faster learning with NPE than PE stimuli. LI deficits in
      schizophrenia may be paradigm-specific and are not detected by a paradigm that we
      previously reported to be sensitive to disruption by dopamine agonists.

PMID- 15560963
TI  - The relationship between visual-perception and attention in Chinese with
      schizophrenia.
AB  - Previous studies suggest possible visual-perceptual deficits associated with
      schizophrenia, and co-existing impairments in attention and visual-perceptual
      function in people with schizophrenia. This study examines if people with
      schizophrenia show visual-perceptual difficulty and whether different components
      of attention, namely sustained attention, selective attention, switching
      attention and attentional control processing, relate to the visual-perceptual
      function of people with schizophrenia differently. A total of 94 participants
      voluntarily participated in this study: 47 of them were diagnosed with
      schizophrenia and 47 were normal controls. Visual-perceptual abilities were
      measured by the Hooper Visual Organization Test (HVOT) for visual organization
      ability and the Judgment of Line Orientation Test (JLOT) for spatial perception
      and orientation. Tests for measuring different components of attention were also
      administered. We observed that our clinical participants performed significantly
      poorer in both the HVOT and the JLOT. We further noticed that nonverbal
      intelligence had a significant influence on our participants' performance in
      these two administered tests. Regarding the relationship between attention and
      visual-perceptual function, our findings indicated that such a relationship
      existed only among our clinical participants, not the normal controls. The
      attention control process significantly predicted the performance in the HVOT and
      switching attention efficiency significantly predicted the performance in the
      JLOT.

PMID- 15560964
TI  - Multisensory integration of emotional faces and voices in schizophrenics.
AB  - In their natural environment, organisms receive information through multiple
      sensory channels and these inputs from different sensory systems are routinely
      combined into integrated percepts. Previously, we reported that in a population
      of schizophrenics, deficits in audiovisual integration were observed for complex
      stimuli (auditory and visual syllables), but not for more simple ones (beeps and
      light flashes). Here, we investigated multisensory integration of emotional
      information in a group of schizophrenic patients. In Experiment 1, we found a
      reduced effect of an emotional voice on the categorization of a facial
      expression. In Experiment 2, the reverse test situation was presented, and, here,
      we observed an exaggerated effect of a face expression on the categorization of
      an emotional voice. Results are discussed in the light of current models of
      multisensory integration and their relevance for schizophrenia.

PMID- 15560965
TI  - Dermatoglyphic anomalies in psychometrically identified schizotypic young adults.
AB  - Dermatoglyphic anomalies are hypothesized to indicate disruptions in the second
      trimester of prenatal development, a time period that appears to be critical in
      the etiology of schizophrenia. The present study examined the presence of
      dermatoglyphic anomalies in psychometrically identified schizotypic young adults
      (n = 51) and control participants (n = 63) selected based upon their scores on
      the Perceptual Aberration [J. Abnorm. Psychology 87 (1978) 399] and Magical
      Ideation Scales [J. Consult. Clin. Psychol. 51 (1983) 215]. It was hypothesized
      that schizotypic participants would exhibit higher rates of dermatoglyphic
      anomalies than control participants. The Perceptual Aberration-Magical Ideation
      group exhibited lower total and absolute finger ridge counts and less complex
      pattern types than control participants--findings consistent with anomalies
      reported in patients with schizophrenia. These findings encourage future
      examination of these anomalies in individuals at-risk for schizophrenia and
      related disorders.

PMID- 15560966
TI  - Schizophrenia patients demonstrate a distinctive pattern of decision-making
      impairment on the Iowa Gambling Task.
AB  - Although dorsolateral prefrontal cortex (DLPFC) abnormalities in schizophrenia
      are well established, several lines of evidence suggest the orbitofrontal cortex
      (OFC) may also be dysfunctional in this disorder. We examined the performance of
      schizophrenia patients and nonpatient controls on the Iowa Gambling Task
      [Cognition 50 (1994) 7], a decision-making task sensitive to OFC damage that
      involves a series of selections from four decks of cards that vary in their
      reward/punishment profiles. Patients also completed neuropsychological tests
      assessing DLPFC functions and clinical symptom assessments. The schizophrenic
      patients demonstrated a pattern of impaired performance that differed both from
      healthy controls and from the "non-conservative" pattern typically found in
      patients with OFC lesions. The patients selected from the two card decks that had
      low frequency and high magnitude punishments significantly more often than the
      decks with high frequency and low magnitude punishments. Performance on the task
      was not strongly related to tests sensitive to DLPFC dysfunction but was
      correlated with negative symptoms. Results suggest that individuals with
      schizophrenia display a pattern of compromised decision-making that is somewhat
      distinct from that found in OFC lesion patients and that may be linked to certain
      clinical symptoms.

PMID- 15560967
TI  - Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy of glutamatergic drugs, acting agonistically
      on the N-methyl-D-aspartate (NMDA) or the non-NMDA receptors, in schizophrenia.
      METHOD: All relevant randomized controlled trials of glutamatergic drugs for
      schizophrenia were obtained from the Cochrane Schizophrenia Group's Register of
      Trials without any language or year limitations. Trials were classified according
      to their methodological quality. For binary and continuous data, relative risks
      and weighted (WMD) or standardized mean differences (SMD) were calculated,
      respectively. RESULTS: Eighteen short-term trials with 343 randomized patients
      were included in the meta-analysis. In all of these trials, glycine, D-serine, D
      cycloserine or ampakine CX516 was used to augment antipsychotics. NMDA receptor
      co-agonists glycine and D-serine are effective in reducing negative symptoms (N =
      132, fixed effect model SMD = -0.66, 95% CI -1.02 to -0.29, p = 0.0004) of
      schizophrenia, the magnitude of the effect is moderate. D-Cycloserine, a partial
      agonist of NMDA receptors, is less effective towards negative symptoms (N = 119,
      fixed effect model SMD = -0.11, 95% CI -0.48 to 0.25, p = 0.6). Positive symptoms
      fail to respond to glutamatergic medication. Available derived data on cognitive
      functioning do not indicate a significant effect of glycine or D-serine (N = 80,
      random effect model WMD = -2.79, 95% CI -6.17 to 0.60, p = 0.11). CONCLUSIONS: In
      the current limited data set, a moderate amelioration of negative symptoms of
      schizophrenia was found, but no other statistically significant beneficial
      effects on symptoms of schizophrenia.

PMID- 15560968
TI  - NMDA hypofunction in the posterior cingulate as a model for schizophrenia: an
      exploratory ketamine administration study in fMRI.
AB  - BACKGROUND: Based on animal data, NMDA receptor hypofunction has been suggested
      as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction
      affects several corticolimbic brain regions, of which the posterior cingulate
      seems to be the most sensitive. However, empirical support for a crucial role of
      posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms
      is still missing in humans. We therefore conducted an fMRI study using the NMDA
      antagonist ketamine in healthy human subjects during episodic memory retrieval,
      which is supposed to activate the posterior cingulate. METHODS: We investigated
      16 healthy subjects which were assigned to either placebo (n = 7; saline) or
      ketamine (n = 9; 0.6 mg/kg/h) group in a double-blind study design. All subjects
      received their infusion while performing an episodic memory retrieval task in the
      scanner. Immediately after the fMRI session, psychopathological effects of
      ketamine were measured using the Altered States of Consciousness Questionnaire.
      RESULTS: The placebo group showed BOLD signal increases in the posterior and
      anterior cingulate during retrieval. Signal increases were significantly lower in
      the ketamine group. Lower signal increases in the posterior cingulate correlated
      significantly with positive (i.e. psychosis-like) symptoms induced by ketamine.
      CONCLUSION: The present study for the first time demonstrates a relationship
      between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like)
      symptoms in humans. Confirming findings from animal studies, it supports the
      hypothesis of a pathophysiological role of NMDA receptor hypofunction in the
      posterior cingulate in schizophrenia.

PMID- 15560969
TI  - Long-acting risperidone vs. placebo in the treatment of hospital inpatients with
      schizophrenia.
AB  - Maintenance treatment regimens for patients with schizophrenia are often
      suboptimal. Partial adherence and outright noncompliance are associated with
      symptom recurrence and increased likelihood of rehospitalization. Long-acting
      conventional neuroleptics have limited efficacy and are associated with treatment
      limiting adverse events, while oral atypical antipsychotics have not improved
      adherence substantially. A long-acting formulation of risperidone, an atypical
      antipsychotic with proven efficacy, has been developed. Introduction of long
      acting injectable treatment may be appropriate during inpatient hospitalization,
      when consequences of relapse are most evident. To support this intervention, a
      subanalysis of patients who were inpatients at study initiation was conducted
      from a 12-week, double-blind, placebo-controlled long-acting risperidone study (N
      = 214). Long-acting risperidone was associated with a significant reduction in
      total Positive and Negative Syndrome Scale (PANSS) score (mean change +/-
      standard error [S.E.] at endpoint: long-acting risperidone, -9.27 +/- 1.44, n =
      133; placebo, 0.72 +/- 2.59, n = 41; P < 0.001), and a significantly higher rate
      of treatment response, defined as > or = 20% reduction in total PANSS score (50%
      vs. 27%, P < 0.05). Significantly more long-acting risperidone patients had
      endpoint Clinical Global Impressions (CGI) assessments of not ill, very mild or
      mild (32% vs. 5%; P < 0.01). Long-acting risperidone was well tolerated. Long
      acting risperidone initiated during inpatient treatment may be an important
      strategy in improving long-term outcomes among patients with schizophrenia.

PMID- 15560970
TI  - Association of plasma apolipoproteins D with RBC membrane arachidonic acid levels
      in schizophrenia.
AB  - Apolipoprotein D (apoD) is a member of the lipocalin superfamily of transporter
      proteins that bind small hydrophobic molecules, including arachidonic acid (AA).
      The ability of apoD to bind AA implicates it in pathways associated with membrane
      phospholipid signal transduction and metabolism. Recent findings of an increased
      expression of apoD in the mouse brain after clozapine treatment suggested a role
      for apoD in the pharmacological action of clozapine. Moreover, clozapine has been
      shown to increase membrane AA levels in RBC phospholipids from schizophrenic
      patients. ApoD levels have also been shown to be elevated in the CNS of subjects
      with chronic schizophrenia, a disorder associated with AA dysfunction. In this
      study, we examined whether plasma apoD levels are related to red blood cell
      membrane AA contents in the first-episode neuroleptic-naive schizophrenic (FENNS)
      patients. Plasma apoD levels as measured by enzyme-linked immunosorbent assay
      (ELISA) were not significantly different (F = 0.51, df = 2,86, p = 0.60) among
      healthy controls (n = 36), FENNS patients (n = 33) and patients with other
      psychiatric disorders (n = 19). However, plasma apoD levels were significantly
      correlated with RBC-AA (p = 0.0022) and docosapentaenoic acid (p = 0.0008) in
      FENNS patients. There are several known mechanisms that can lead to the type of
      membrane fatty acid defects that have been identified in schizophrenia. Whether
      plasma apoD alone is a major determinant of reduced RBC membrane AA levels in
      FENNS patients remains to be determined, although these preliminary data appear
      not to support this premise. Taken together with other in vitro studies, however,
      the present data support the view that an increased expression of apoD such as
      induced by atypical neuroleptic drug, may facilitate incorporation of AA into
      membrane phospholipids by its selective binding to AA.

PMID- 15560971
TI  - Mitochondrial genes and schizophrenia.

PMID- 15560972
TI  - Genes in families: attitudes toward genetic testing for schizophrenia.

PMID- 15560973
TI  - Mutation analysis of ARVCF gene on chromosome 22q11 as a candidate for a
      schizophrenia gene.

PMID- 15560974
TI  - The contribution of a modified transactional model to the adaptation of
      schizophrenics living in the city of Montreal.

PMID- 15560975
TI  - Pharmaceutical biotechnology.

PMID- 15560976
TI  - Modified vaccinia virus Ankara as antigen delivery system: how can we best use
      its potential?
AB  - Safety-tested modified vaccinia virus Ankara (MVA) has been established as a
      potent vector system for the development of candidate recombinant vaccines. The
      versatility of the vector system was recently demonstrated by the rapid
      production of experimental MVA vaccines for immunization against severe acute
      respiratory syndrome associated coronavirus. Promising results were also obtained
      in the delivery of Epstein-Barr virus or human cytomegalovirus antigens and from
      the clinical testing of MVA vectors for vaccination against immunodeficiency
      virus, papilloma virus, Plasmodium falciparum or melanoma. Moreover, MVA is
      considered to be a prime candidate vaccine for safer protection against
      orthopoxvirus infections. Thus, vector development to challenge dilemmas in
      vaccinology or immunization against poxvirus bio-threat seems possible, yet the
      right choice should be made for a most beneficial use.

PMID- 15560977
TI  - Virus-like particles as vaccines and vessels for the delivery of small molecules.
AB  - Virus-like particles (VLPs) structurally mimic the viral capsid and have
      therefore been extensively, and quite successfully, used as vaccine and viral
      serology reagents. The ability of VLPs to include nucleic acids and small
      molecules has also made them novel vessels for gene and drug delivery. The
      regular, repetitive surface of VLPs has been exploited as a template for
      nanoscale synthesis. Recent progress has been made in the development of several
      virus models.

PMID- 15560978
TI  - Liposomes and virosomes as delivery systems for antigens, nucleic acids and
      drugs.
AB  - Lipid-based vesicles are a very promising approach to treat diseases such as
      cancer, chronic infections and auto-immunity. Modern drug encapsulation methods
      allow efficient packing of therapeutic substances inside liposomes, thereby
      reducing the systemic toxicity of the drugs. Specific targeting can enhance the
      therapeutic effect of the drugs through their accumulation at the diseased site.
      In the vaccine field, the integration of functional viral envelope proteins into
      liposomes has led to an antigen carrier and delivery system termed a virosome, a
      clinically proven vaccine platform for subunit vaccines with an excellent
      immunogenicity and tolerability profile.

PMID- 15560979
TI  - Bacterial ghosts--biological particles as delivery systems for antigens, nucleic
      acids and drugs.
AB  - Despite the exponential rate of discovery of new antigens and DNA vaccines
      resulting from modern molecular biology and proteomics, the lack of effective
      delivery technology is a major limiting factor in their application. The
      bacterial ghost system represents a platform technology for antigen, nucleic acid
      and drug delivery. Bacterial ghosts have significant advantages over other
      engineered biological delivery particles, owing to their intrinsic cellular and
      tissue tropic abilities, ease of production and the fact that they can be stored
      and processed without the need for refrigeration. These particles have found both
      veterinary and medical applications for the vaccination and treatment of tumors
      and various infectious diseases.

PMID- 15560980
TI  - Targeting split vaccines to the endosome improves vaccination.
AB  - Compared to 'live' vaccines, the immunogenicity of 'split' vaccines based on
      recombinant antigen (Ag) is poor, presumably because exogeneous recombinant Ag
      fails to efficiently access the major histocompatibility complex (MHC) class I
      processing pathway needed for 'cross-presentation'. Here we discuss recent
      evidence that targeting ligands of the Toll-like receptor 9 together with
      proteinaceous Ag to the endosome of dendritic cells conveys immunogenicity to Ag
      similar in magnitude to 'live' vaccines that produce Ag. Enforced endocytosis of
      Ag together with the adjuvant effect of Toll-like receptor 9 ligands might be key
      for the efficient cross-presentation of exogeneous Ag as well as for effective
      cross-priming of MHC class I restricted CD8 T effector cells.

PMID- 15560981
TI  - Nonstructural HIV proteins as targets for prophylactic or therapeutic vaccines.
AB  - By the end of 2004, more than 20 HIV-1 vaccine candidates will have entered
      clinical testing in at least 30 trials worldwide. Almost half of these vaccines
      include nonstructural HIV-1 gene products. This represents an important
      innovation in the HIV vaccine field, because until 9 years ago not even
      preclinical testing in small animal models had been carried out with such
      immunogens. This review briefly discusses the experimental evidence that provides
      the rationale for the use of nonstructural HIV-1 gene products as vaccine
      antigens, and summarizes the current status and the future development of these
      novel vaccines.

PMID- 15560982
TI  - Tumour necrosis factor alpha as a therapeutic target for immune-mediated
      inflammatory diseases.
AB  - Preclinical studies have identified and validated tumour necrosis factor alpha
      (TNFalpha) as a key disease molecule and therapeutic target for immunotherapeutic
      intervention in many immune-mediated inflammatory diseases. Clinical indications
      include rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and
      psoriasis. Recent clinical findings indicate that many chronic inflammatory
      disorders share certain pathogenic pathways, whereas others are limited to
      particular disease phenotypes. Better understanding of these pathogenic pathways
      will inform the development of new therapeutic approaches leading to more
      complete and sustained disease remissions.

PMID- 15560983
TI  - Technology for high-throughput screens: the present and future using zebrafish.
AB  - The zebrafish is a popular vertebrate model organism with similar organ systems
      and gene sequences to humans. Zebrafish embryos are optically transparent
      enabling organ visualisation, which can be complemented with gene expression
      analysis at the transcript and protein levels. Furthermore, zebrafish can be
      treated with small molecules and drugs in a microtitre plate format for high
      throughput analysis and for the identification and validation of drugs. High
      throughput methodologies for use in zebrafish include phenotype-based
      visualisation, transcript studies using low-density DNA microarrays and proteomic
      analysis. These technologies offer significant whole-organism biological value in
      the drug discovery and drug development pipeline.

PMID- 15560984
TI  - Be inspired -- chemical and functional diversity of new natural product born
      structures.

PMID- 15560985
TI  - Small-molecule natural products: new structures, new activities.
AB  - A wide variety of novel small-molecule natural products has recently been
      reported. These compounds were isolated from marine and terrestrial sources, and
      from a variety of animals, plants and microorganisms. With the breadth of
      diversity represented in these bioactive small molecules, the future of natural
      product drug discovery looks bright.

PMID- 15560986
TI  - Natural products as a hunting ground for combinatorial chemistry.
AB  - Natural products have a long history of success as biologically active leads for
      therapeutic agents. The ability to prepare analogues and to discover structure
      activity relationships is necessary to truly harness the potential of natural
      products. Recently, combinatorial chemistry has risen to this challenge, and even
      fairly complex natural products can be targeted for parallel synthesis. Academic
      and industrial efforts have employed natural products from the peptide, alkaloid,
      polyketide, and terpenoid and steroid classes in combinatorial chemistry
      approaches for the production of medicinally important compounds.

PMID- 15560987
TI  - Chemical diversity through biotransformations.
AB  - Diversity constitutes an intrinsic property of biosynthesis. This inherent
      property can be exploited and successfully applied in organic synthesis. Recent
      advances have been made in many areas, including the use of multifunctional
      enzymes and catalytic promiscuity, the synthesis of diverse products from a
      single substrate, the use of different biotransformations to make one product,
      and the use of in vivo biotransformations.

PMID- 15560988
TI  - Exploiting natural peptide diversity: novel research tools and drug leads.
AB  - During the course of evolution, nature has developed a vast number of peptides in
      all living and past species that display an exceeding diversity of structure and
      biological effects, such as hormonal and enzyme-controlling activity,
      communication between cells, and participation in host defence. Sensitive mass
      spectrometric technologies have been introduced and facilitate access to new
      natural peptides, even in trace amounts, and allow the quantitative determination
      of the peptide status of cells, organs and whole organisms (peptidomics). Among
      the large number of new biologically active peptides identified from an
      increasing variety of natural sources, regulators of ion channels,
      chemoattractants, protease inhibitors, metabolism-related hormones, cytotoxins,
      and antimicrobials have been found. These novel peptides serve as research tools
      and have potential as diagnostic biomarkers and for the development of peptide
      and peptidometic drugs.

PMID- 15560989
TI  - Novel forms of chemical protein diversity -- in nature and in the laboratory.
AB  - Novel chemical variants of proteins have been found in nature, including potent
      'microprotein' natural products and folded protein molecules that contain a
      cyclic polypeptide chain. Researchers have used chemical synthesis and genetic
      methods to make these proteins and more: protein catenanes, neoglycoproteins, and
      artificial protein molecules with novel architectures or made from novel building
      blocks. De novo design has taken a big step forward with the accurate design and
      construction of proteins with complex molecular structure. A variety of non-coded
      amino acids and other building blocks has been used to make increasingly
      sophisticated protein molecular devices for use as biosensors and for the study
      of signal transduction inside living cells.

PMID- 15560990
TI  - Carbohydrate diversity: synthesis of glycoconjugates and complex carbohydrates.
AB  - The fundamental role of glycoconjugates in many biological processes is now well
      appreciated and has intensified the development of innovative and improved
      synthetic strategies. All areas of synthetic methodology have seen major advances
      and many complex, highly branched carbohydrates and glycoproteins have been
      prepared using solution- and/or solid-phase approaches. The development of an
      automated oligosaccharide synthesizer provides rapid access to biologically
      relevant compounds. These chemical approaches help to produce sufficient
      quantities of defined oligosaccharides for biological studies. Synthetic
      chemistry also supports an improved understanding of glycobiology and will
      eventually result in the discovery of new therapeutics.

PMID- 15560991
TI  - Calcifying fibrous pseudotumor of the pleura.
AB  - Calcifying fibrous pseudotumor is an uncommon benign lesion that has unique
      histologic features. We report a case of calcifying fibrous pseudotumor of the
      pleura occurring in a 31-year-old woman. A computed tomographic scan revealed a
      pleural mass in the right anterior costophrenic angle. The excised mass was well
      circumscribed, nonencapsulated, solid, and firm. The tumor showed dense
      hyalinized collagenous tissue interspersed with spindle cells, psammomatous
      calcifications, and a predominantly lymphoplasmocytic infiltrate. Most spindle
      cells were diffusely positive for vimentin, focally positive for CD34, and
      negative for desmins, smooth muscle actin, S-100 protein, and anaplastic lymphoma
      kinase-1.

PMID- 15560992
TI  - Severe argatroban-induced coagulopathy in a patient with a history of heparin
      induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia is a serious complication of heparin therapy,
      and it remains a therapeutic challenge in the subset of patients requiring
      cardiopulmonary bypass. Alternative anticoagulation strategies include lepirudin,
      danaparoid, bivalirudin, and argatroban, or a combination of unfractionated
      heparin with a platelet antagonist. Argatroban is eliminated by a hepatic route,
      making it a practical option for patients with renal insufficiency. However, the
      lack of an effective antidote poses a significant problem. We present a patient
      with a history of heparin-induced thrombocytopenia with thrombosis who underwent
      a redo aortic valve replacement. Although the level of anticoagulation achieved
      with argatroban was initially adequate, its persistence after the completion of
      cardiopulmonary bypass proved to be life threatening.

PMID- 15560993
TI  - Use of the Alfieri edge-to-edge technique to eliminate left ventricular outflow
      tract obstruction caused by mitral systolic anterior motion.
AB  - A 68-year-old woman with concentric left ventricular hypertrophy, prosthetic
      valve endocarditis with aortic root abscess, and sepsis had aortic root
      replacement with an aortic allograft. On weaning from cardiopulmonary bypass, she
      had hemodynamic instability caused by systolic anterior motion of the mitral
      valve, which resulted in a left ventricular outflow tract obstruction; the peak
      pressure gradient across the left ventricular outflow tract was 130 mm Hg, and
      there was moderately severe (3+) mitral regurgitation. After reinstitution of
      cardiopulmonary bypass, a central Alfieri edge-to-edge stitch was placed between
      the anterior and posterior leaflets of the mitral valve. This reduced the
      gradient across the left ventricular outflow tract to 10 mm Hg and eliminated the
      mitral regurgitation, which enabled successful separation from cardiopulmonary
      bypass.

PMID- 15560994
TI  - Saccular aneurysm of the superior vena cava detected by computed tomography and
      successfully treated with surgery.
AB  - Vascular lesions must be considered in the differential diagnosis of mediastinal
      masses. Systemic venous aneurysms are an extremely rare cause of dilatation of
      the mediastinal shadow on plain chest roentgenograms. We describe what we believe
      to be the 10th case in the literature of a saccular aneurysm of the superior vena
      cava, which was detected by computed tomography in a 59-year-old woman and was
      successfully treated with surgery.

PMID- 15560995
TI  - Cardiac varix in relation to right atrial free wall presenting as a mass
      compressing the right atrium and mimicking a pericardial cyst.
AB  - Cardiac varix is a rare entity. It is generally small and is in relation to the
      interatrial septum, often mistaken as cardiac myxoma. A 19-year-old girl, on
      evaluation of respiratory infection, was found to have a mass compressing the
      right atrium. Computed tomographic scan and magnetic resonance imaging suggested
      a differential diagnosis of pericardial cyst or hydatid cyst. Peroperatively, a
      large (8 x 6.5 x 5.5 cm) cystic lesion in relation to the right atrial free wall
      was found. The histopathology of the resected mass revealed it to be a cardiac
      varix. The case is notable for its large size and its location in relation to the
      right atrial free wall.

PMID- 15560996
TI  - Long-term survival after resection of primary adenoid cystic and squamous cell
      carcinoma of the trachea and carina.
AB  - BACKGROUND: Tracheal resection for primary carcinoma may extend survival. We
      evaluated survival after surgical resection or palliative therapy to identify
      prognostic factors. METHODS: We conducted a retrospective study of patients
      diagnosed with primary adenoid cystic carcinoma (ACC) or squamous cell carcinoma
      (SCC) of the trachea between 1962 and 2002. Laryngotracheal, tracheal, or carinal
      resection was performed when distant metastasis and invasion of adjacent
      mediastinal structures were absent and tumor length permitted. Radiotherapy was
      administered after operation (54 Gy), except in superficial tumors, or as
      palliation (60 Gy). RESULTS: Of 270 patients with ACC or SCC (135 each), 191
      (71%) were resected. Seventy-nine were not resected due to tumor length (67%),
      regional extent (24%), distant metastasis (7%), or other reasons (2%). Overall
      operative mortality was 7.3% (14/191) and improved each decade from 21% to 3%.
      Tumor in airway margins was present in 40% (17/191) of resected patients (ACC 59%
      versus SCC 18%) and lymph node metastasis in 19.4% (37/191). Overall 5- and 10
      year survival in resected ACC was 52% and 29% (unresectable 33% and 10%) and in
      resected SCC 39% and 18% (unresectable 7.3% and 4.9%). Multivariate analysis of
      long-term survival found statistically significant associations with complete
      resection (p < 0.05), negative airway margins (p < 0.05), and adenoid cystic
      histology (p < 0.001), but not with tumor length, lymph node status, or type of
      resection. CONCLUSIONS: Locoregional, not distant, disease determines
      resectability in primary tracheal carcinoma. Resection of trachea or carina is
      associated with long-term survival superior to palliative therapy, particularly
      for patients with complete resection, negative airway margins, and ACC.

PMID- 15560997
TI  - Medium-term follow-up after deployment of ultraflex expandable metallic stents to
      manage endobronchial pathology.
AB  - BACKGROUND: Between March 1997 and March 2004 we deployed 80 Ultraflex metallic
      expandable stents (Boston Scientific, Waterson, MA) in 69 patients under direct
      vision using rigid bronchoscopy. We report our medium- to long-term experience in
      patients for whom these stents were deployed. METHODS: To date 15 patients have
      been followed for more than 1 year (median 41 months, range 12 to 83 months)
      after stent deployment. Indications for stenting in these patients were neoplasia
      (5), stricture (5), airway malacia (1), iatrogenic tracheal tear (1), and
      compression from an aortic aneurysm (1), a right interrupted aortic arch (1), and
      a right brachiocephalic artery aneurysm with tracheomalacia (1). Ten tracheal
      stents (9 covered, 1 uncovered) and 10 bronchial stents (8 uncovered, 2 covered)
      were inserted, and 5 patients received two stents. RESULTS: Five of these
      patients experienced no long-term problems. Complications included troublesome
      halitosis (5), which was difficult to treat despite various antibiotic regimes;
      granulation tissue formation above and below the stent that was successfully
      treated with low-power Nd:YAG laser therapy (7); and metal fatigue (1). We did
      not encounter stent migration. CONCLUSIONS: We conclude that Ultraflex expandable
      metallic stents have an important role in the management of selected patients
      with diverse endobronchial pathologies and are well tolerated in the long-term.
      Although associated granulation tissue can be successfully treated with Nd:YAG
      laser, halitosis can be a difficult problem to address.

PMID- 15560998
TI  - Repeat FDG-PET after neoadjuvant therapy is a predictor of pathologic response in
      patients with non-small cell lung cancer.
AB  - BACKGROUND: Repeat positron emission tomography (PET) with 18F-fluorodeoxyglucose
      (FDG) and chest computed tomography (CT) are used to assess the effectiveness of
      chemoradiotherapy in patients with non-small cell lung cancer (NSCLC); however,
      the change in the standardized uptake values (SUV) has not been correlated with
      the pathologic change of the primary tumor. METHODS: This is a retrospective
      cohort study of a prospective database of 56 patients who had NSCLC, FDG-PET, and
      chest CT scans both before and after neoadjuvant therapy, followed by complete
      resection of their cancer. Maximum SUVs (maxSUV) and tumor size were measured,
      and the percentage of change was compared with the percentage of nonviable tumor
      cells. The primary objective was to measure the degree of correlation between
      these values. RESULTS: The change in the maxSUV has a near linear relationship to
      the percent of nonviable tumor cells in the resected tumors. FDG-PET's maxSUV is
      better correlated to pathology than the change in size on CT scan (r2 = 0.75, r2
      = 0.03, p < 0.001). When the maxSUV decreased by 80% or more, a complete
      pathologic response could be predicted with a sensitivity of 90%, specificity of
      100%, and accuracy of 96%. CONCLUSIONS: The change in maxSUV on FDG-PET scan
      after neoadjuvant therapy holds a near linear relationship with pathologic
      response. It is a more accurate predictor than the change of size on CT scan.
      When the maxSUV decreases by 80% or more it is likely that the patient is a
      complete responder irrespective of cell type, neoadjuvant treatment, or the final
      absolute maxSUV. These findings may help guide treatment strategies.

PMID- 15561000
TI  - Accuracy of helical CT in the detection of pulmonary metastases: is
      intraoperative palpation still necessary?
AB  - BACKGROUND: Pulmonary metastasectomy is well accepted in patients with isolated
      metastases from an extrathoracic malignancy. The standard approach involves
      careful intraoperative palpation of the lungs because more metastases are
      frequently found than were seen by preoperative conventional computed tomography
      (CT). Helical CT detects more nodules than conventional CT, raising the question
      of whether palpation of the lungs is still necessary if helical CT is used.
      METHODS: Retrospective review was done of medical records of patients undergoing
      metastasectomy with curative intent at the University of North Carolina (UNC)
      from 1999 to 2003. During this time at UNC, helical CT was routinely performed
      using a standardized technique, and all metastasectomy patients underwent manual
      lung palpation. The primary outcome measure of this study was whether malignant
      nodules (palpated, resected, and proven histologically) were reliably detected
      preoperatively by helical CT. RESULTS: Thirty-four patients were identified who
      underwent 41 cases of pulmonary metastasectomy with lung palpation. Our analysis
      revealed that in 22% (9/41), more malignant nodules were found intraoperatively
      than were detected by helical CT. Of 88 malignant intraparenchymal nodules, 69
      were detected by helical CT (sensitivity 78%). Subset analyses of tumor
      histology, disease-free interval, the presence of a single lesion versus multiple
      lesions, the interval between the CT and metastasectomy, and the size of the
      largest lesion were unable to identify a cohort in which lung palpation was no
      longer needed after preoperative helical CT. CONCLUSIONS: Despite the advent of
      helical CT, palpation of the lung is necessary if the goal is to resect all
      detectable disease.

PMID- 15561001
TI  - Isolated lung perfusion with melphalan for resectable lung metastases: a phase I
      clinical trial.
AB  - BACKGROUND: Current 5-year survival after complete resection of pulmonary
      metastases is 20% to 40%, and many patients develop intrathoracic recurrences.
      Isolated lung perfusion is an experimental technique to deliver high-dose
      chemotherapy to the lung without systemic exposure. A phase I trial of isolated
      lung perfusion with melphalan (MN) combined with pulmonary metastasectomy for
      resectable lung metastases was conducted to define the dose-limiting toxicity and
      maximum tolerated dose. METHODS: From May 2001 to August 2003, 16 patients
      underwent isolated lung perfusion with MN, followed by surgical resection of lung
      metastases. Patients were treated with increasing MN doses (15, 30, 45, and 60
      mg). For each dose level, normothermia (37 degrees C) and hyperthermia (42
      degrees C) were evaluated (n = 3 per level). Serum samples were obtained during
      the procedure. Pulmonary, hematologic, and nonhematologic toxicities were
      recorded. The primary tumor was colorectal in 7 patients, renal in 5, sarcoma in
      3, and salivary gland in 1. Isolated lung perfusion was performed unilaterally in
      11 patients, and staged bilaterally in 5. RESULTS: In total, 21 procedures of
      isolated lung perfusion with complete metastasectomy were performed without
      technical difficulties. Operative mortality was 0%, and no systemic toxicity was
      encountered. Grade 3 pulmonary toxicity developed at a dose of 60 mg of MN at 37
      degrees C in 2 of 3 patients at this dose, terminating the trial. CONCLUSIONS:
      Isolated lung perfusion with MN combined with pulmonary metastasectomy is
      feasible. Dose-limiting toxicity occurred at a dose of 60 mg of MN at 37 degrees
      C, and the maximum tolerated dose was set at 45 mg of MN at 42 degrees C.

PMID- 15561002
TI  - Clinicopathological analysis of pulmonary sclerosing hemangioma.
AB  - BACKGROUND: Sclerosing hemangiomas of the lung are uncommon tumors and are
      thought to be benign. However, the histogenesis and clinicopathological features
      of these tumors have not been elucidated. METHODS: We analyzed the
      clinicopathological features of 26 sclerosing hemangiomas. The immunoreactivity
      for Ki-67 and p53 of sclerosing hemangiomas was determined and compared with that
      of pathological stage 1 pulmonary papillary adenocarcinomas. RESULTS: The
      patients of sclerosing hemangioma were predominantly female. Eighteen patients
      were detected as a result of routine medical examinations and 15 were nonsmokers.
      Seven patients underwent tumor enucleation, 10 underwent a wedge resection, and 9
      underwent a lobectomy. The mean tumor size was 2.2 cm (range 1 to 5 cm).
      Pathological findings demonstrated a papillary pattern in 23 cases, sclerotic
      pattern in 26 cases, hemorrhagic pattern in 22 cases and a solid pattern in 25
      cases. Twenty-five cases had an excellent prognosis with no evidence of
      recurrence following surgery. However, 1 patient who had undergone a wedge
      resection developed a local recurrence and required an additional wedge
      resection. The Ki-67 labeling index of sclerosing hemangiomas was significantly
      lower than that of adenocarcinomas, whereas the Ki-67 labeling index of the
      recurrent case was 0.4%. No significant immunohistochemical staining for p53 was
      observed in sclerosing hemangioma cases. CONCLUSIONS: Sclerosing hemangioma
      exhibits various histologic findings. Although we experienced one case with a
      recurrent tumor, sclerosing hemangiomas did not exhibit malignant behavior.

PMID- 15561003
TI  - Endobronchial gene transfer of soluble type I interleukin-1 receptor ameliorates
      lung graft ischemia-reperfusion injury.
AB  - BACKGROUND: Soluble type I interleukin-1 receptor is a competitive inhibitor of
      interleukin-1 and may reduce its proinflammatory actions. The objective of this
      experiment was to demonstrate that endobronchial gene transfer of soluble type I
      interleukin-1 receptor IgG to donor lung grafts reduces posttransplant ischemia
      reperfusion injury. METHODS: All experiments utilized an orthotopic left lung
      isograft transplant model. Donors were divided into three groups (n = 6 each) for
      endobronchial transfection: group I received 2 x 10(7) plaque-forming units of
      adenovirus encoding soluble type I interleukin-1 receptor IgG; group II received
      2 x 10(7) plaque-forming units of nonfunctional control adenovirus encoding beta
      galactosidase; and group III received 0.1 mL of saline. Left lungs were harvested
      24 hours after transfection and stored for 18 hours before transplantation. Graft
      function was assessed 24 hours after reperfusion using three measurements:
      isolated graft oxygenation, wet-to-dry lung weight ratio, and tissue
      myeloperoxidase activity. Transgene expression of soluble type I interleukin-1
      receptor IgG was also evaluated using enzyme-linked immunosorbent assay and
      immunohistochemistry. RESULTS: Isolated graft arterial oxygenation was
      significantly improved in group I compared with groups II and III (281.8 +/-
      134.8 versus 115.7 +/- 121.5 and 88.0 +/- 58.9 mm Hg, p = 0.0197 and p = 0.0081,
      respectively). Myeloperoxidase activity was also significantly reduced in group I
      compared with groups II and III (0.083 +/- 0.044 versus 0.155 +/- 0.043 and 0.212
      +/- 0.079 optical density units per minute per milligram protein, p = 0.0485 and
      p = 0.0016, respectively). Expression of soluble type I interleukin-1 receptor
      IgG was detected only in lungs from group I. CONCLUSIONS: Endobronchial gene
      transfer of soluble type I interleukin-1 receptor IgG to donor lung grafts
      subjected to prolonged cold ischemia ameliorates ischemia-reperfusion injury by
      improving graft oxygenation and reducing lung edema and neutrophil sequestration.

PMID- 15561004
TI  - Recovery of chronic renal impairment with sirolimus after lung transplantation.
AB  - BACKGROUND: Standard immunosuppression after lung transplantation includes
      calcineurin inhibitors, azathioprine, and steroids. Calcineurin inhibitor
      administration is associated with an increased renal impairment. Sirolimus shows
      no renal toxicity and could be used in selected patients. METHODS: We have
      prospectively administered sirolimus as an alternative to calcineurin inhibitors
      in 15 lung transplantation recipients with persistent drug nephrotoxicity. Eight
      patients had also bronchiolitis obliterans syndrome. The mean serum creatinine
      and azotemia were 2.7 +/- 1.1 mg/dL and 111 +/- 39 mg/dL. After starting
      sirolimus, azathioprine was reduced to 50%-25% of baseline, calcineurin
      inhibitors were gradually reduced and eventually stopped, and steroids were
      maintained stable. Patients started sirolimus with 2 to 5 mg/d orally;
      adjustments were made according to trough levels (4 to 12 ng/mL for combined
      sirolimus + calcineurin inhibitors; 12 to 20 ng/mL as monotherapy), toxicity, and
      perceived efficacy. Patients were monitored for renal and graft function and
      clinical status. RESULTS: A significant creatinine decrease was observed after 6
      months of treatment (p < 0.02); azotemia decreased after 1 month and remained
      stable (p < 0.01). Pulmonary function tests did not show any significant
      modification from before sirolimus baseline in patients without bronchiolitis
      obliterans syndrome. There were eight infectious complications and 10 episodes of
      toxicity (4 dermatitis, 2 epistaxis, 1 headache, 1 diarrhea, 1 nausea, 1
      laryngeal cancer). Moderate leukocytopenia (n = 3) and hypertriglyceridemia (n =
      6) responded to dose reduction. One patient was lost to follow-up. Three patients
      died of complications related to bronchiolitis obliterans. One patient underwent
      transplantation again. CONCLUSIONS: Sirolimus administration allows amelioration
      of renal function with a relatively low morbidity and is useful for chronic renal
      impairment rescue after lung transplantation.

PMID- 15561005
TI  - Bone marrow micrometastases and markers of angiogenesis in esophageal cancer.
AB  - BACKGROUND: Tumor angiogenesis is critical for metastasis development. The
      detection of bone marrow micrometastases may indicate a metastatic phenotype. We
      aim to establish if the detection of bone marrow micrometastases associates with
      elevated markers of angiogenesis and adverse histopathologic features of
      esophageal cancer. METHODS: Bone marrow aspirates from 49 patients with
      esophageal cancer were assessed and assigned to be positive or negative for
      micrometastases. Routine histologic assessment of the primary tumor was also
      undertaken. Circulating and tumor levels of the angiogenic cytokine vascular
      endothelial growth factor were determined in plasma and tumor homogenate.
      Intratumor microvessel density was evaluated by counting anti-CD34 positive
      neovessels. RESULTS: Twenty-two patients were positive for bone marrow
      micrometastases (44.9%). The detection of micrometastases was associated with
      advanced T stage (T3/4 vs T1/2; p = 0.023), circumferential margin involvement (p
      = 0.002) and lymphovascular invasion (p = 0.024). Plasma vascular endothelial
      growth factor was significantly more elevated in micrometastatic-positive
      patients than in those without micrometastases (p = 0.018). No difference was
      noted in tumor vascular endothelial growth factor expression. For adenocarcinomas
      alone, intratumor microvessel density was significantly higher in micrometastatic
      positive cases (p = 0.03). This was not the case for squamous cell carcinomas.
      CONCLUSIONS: The detection of bone marrow micrometastases is associated with
      esophageal tumors of advanced T stage and specifically for adenocarcinomas with
      tumor vascularity. Plasma vascular endothelial growth factor is elevated in
      micrometastatic positive cases and might be derived from sources other than the
      primary tumor.

PMID- 15561007
TI  - Outcome of right ventricle-to-pulmonary artery shunt in first-stage palliation of
      hypoplastic left heart syndrome: a multi-institutional study.
AB  - BACKGROUND: To evaluate the developing surgical technique of a modified Norwood
      procedure using a right ventricle-to-pulmonary artery shunt, we analyzed data
      obtained from 73 infants who underwent first-stage palliation for hypoplastic
      left heart syndrome between 1998 to 2002 at three centers in Japan. METHODS:
      Procedures performed included an aortopulmonary neoaortic reconstruction and a
      nonvalved polytetrafluoroethylene shunt between a small right ventriculotomy and
      a distal stump of the main pulmonary artery. The size of the shunt used was 4 mm
      in 6 patients, 5 mm in 41, and 6 mm in 26. Continuous cerebral perfusion was used
      in all patients and an additional descending aortic perfusion was used in 39.
      Postoperative management was basically the same as that for infants undergoing
      other types of operations. RESULTS: There were 61 hospital survivors (84%),
      including 5 of 6 patients weighing less than 2 kg, with 8 late deaths. Risk
      factors for hospital mortality include preoperative treatment without ventilatory
      support and surgeon's experience (first 10 cases). Three patients underwent a
      primary Fontan operation at 5, 9, and 10 months of age, with one late death.
      Forty-one patients underwent the bidirectional Glenn shunt after a mean interval
      of 6.9 months, and 19 of them completed the Fontan operation at median age of 2.1
      years. Overall survivals were 65% at 1 year and 63% at 2 years. CONCLUSIONS:
      Improved survival for patients after first-stage palliation of hypoplastic left
      heart syndrome is reproducible for many centers by an application of the modified
      Norwood procedure with the right ventricle-to-pulmonary artery shunt.

PMID- 15561008
TI  - Right ventricle to pulmonary artery conduit reduces interim mortality after stage
      1 Norwood for hypoplastic left heart syndrome.
AB  - BACKGROUND: Despite significant improvement in survival after stage 1 Norwood,
      interim mortality before the second-stage operation remains significant. On the
      basis of reports of improved circulatory stability associated with the use of a
      right ventricle to pulmonary artery conduit, the difference between two
      physiologically different sources of pulmonary blood flow on interim mortality
      was investigated. METHODS: Data collection of 96 consecutive hospital survivors
      after stage 1 Norwood surgery was undertaken. The source of pulmonary blood flow
      was a modified right Blalock-Taussig shunt in 46 (BTS) and a right ventricle to
      pulmonary artery conduit in 50 patients. The same follow-up protocol was used in
      both groups. Data analysis was performed to identify variables associated with
      interim mortality. RESULTS: Analysis of patient-related and procedure-related
      variables revealed no differences in age, weight, diagnosis, presence of aortic
      atresia, lowest perioperative pH, duration of cardiopulmonary bypass, circulatory
      arrest, length of mechanical ventilation, or hospital stay at the time of stage 1
      Norwood between groups. Respiratory rate and systolic blood pressure were the
      only differences detected between groups at the time of discharge. Interim
      mortality was higher in the Blalock-Taussig shunt group. Statistical analysis
      identified aortic atresia, a modified Blalock-Taussig shunt, and the presence of
      perioperative dysrhythmias to be associated with interim mortality. CONCLUSIONS:
      The use of a right ventricle to pulmonary artery shunt decreases the incidence of
      interim mortality among hospital survivors after stage 1 Norwood for hypoplastic
      left heart syndrome. Aortic atresia, the use of a modified Blalock-Taussig shunt,
      and perioperative dysrhythmias are independently associated with a higher
      mortality before superior cavopulmonary connection.

PMID- 15561009
TI  - Midterm ventricular performance after Norwood procedure with right ventricular
      pulmonary artery conduit.
AB  - BACKGROUND: Midterm and long-term results of patients who underwent a Norwood
      procedure with a right ventricular-pulmonary artery conduit remain unclear. This
      study aimed to compare the midterm ventricular performance of the Norwood
      procedure with right ventricular-pulmonary artery conduit and the Norwood
      procedure with systemic-pulmonary shunt. METHODS: Twenty-one patients who
      underwent both a bidirectional Glenn procedure and a total cavopulmonary
      connection after Norwood palliation at Fukuoka Children's Hospital Medical Center
      were divided into two groups: the systemic-pulmonary shunt group (n = 11) and the
      right ventricular-pulmonary artery conduit group (n = 10). End-systolic elastance
      (contractility), effective arterial elastance (afterload), and ventriculoarterial
      coupling and the ratio of stroke work and pressure-volume area (ventricular
      efficiency) were measured on the basis of cardiac catheterization data before the
      bidirectional Glenn procedure, before and after the total cavopulmonary
      connection, and at approximately 1 year after total cavopulmonary connection.
      RESULTS: After bidirectional Glenn procedure and total cavopulmonary connection,
      end-systolic elastance of the right ventricular-pulmonary artery conduit group
      was lower than that of the systemic-pulmonary shunt group, whereas effective
      arterial elastance of the right ventricular-pulmonary artery conduit group was
      lower than that of the systemic-pulmonary shunt group. Consequently, there was no
      difference in ventricular efficiency in both groups 1 year after total
      cavopulmonary connection. CONCLUSIONS: The midterm ventricular performance of the
      right ventricular-pulmonary artery conduit group was comparable with the systemic
      pulmonary shunt group in terms of ventricular efficiency. However, after
      bidirectional Glenn procedure and total cavopulmonary connection, contractility
      in patients who underwent a Norwood procedure with a right ventricular-pulmonary
      artery conduit was inferior to that of patients who underwent a Norwood procedure
      with a systemic-pulmonary shunt.

PMID- 15561011
TI  - Risk factors for readmission after neonatal cardiac surgery.
AB  - BACKGROUND: Repeat hospitalizations place a significant burden on health care
      resources. Factors predisposing infants to unplanned hospital readmission after
      congenital heart surgery are unknown. METHODS: This is a single-center, case
      control study. Cases were rehospitalized or died within 30 days of discharge
      following an arterial switch operation (ASO) or Norwood procedure (NP) between
      1992 and 2002. Controls underwent an ASO or NP between 1992 and 2002, and were
      neither readmitted nor died within 30 days of discharge. Patients and controls
      were matched by gender, year of birth, and procedure. Potential risk factors
      examined included indices of medical status at the time of discharge,
      determinants of access to health care, and provider characteristics. RESULTS:
      Forty-eight patients were readmitted; 19 of 498 (3.8%) following an ASO and 29 of
      254 (11.4%) after a NP (p < 0.001). Six infants died within 30 days of discharge;
      1 after an ASO and 5 after a NP. In multivariate analysis, predictors of
      readmission or death were: residual hemodynamic problem(s) (odds ratio [OR] 4.10
      [1.18, 14.3], p = 0.026); an intensive care unit stay greater than 7 days (OR
      5.17 [1.12, 23.9] p = 0.035) (ASO); residual hemodynamic problem(s) (OR 5.84
      [1.98, 17.2], p = 0.001); and establishment of full oral intake less than 2 days
      before discharge (OR 5.83 [1.83, 18.6], p = 0.003) (NP). Combining both groups,
      living in a low income Zip Code (< 30,000 dollars/annum) was associated with a
      lower likelihood of readmission (OR 0.25 [0.07, 0.85], p = 0.027). CONCLUSIONS:
      Residual hemodynamic problem(s) predispose to hospital readmission after the ASO
      and NP. Low socioeconomic status may reduce the likelihood of readmission even
      when problems arise.

PMID- 15561013
TI  - New onset arrhythmias after the extracardiac conduit Fontan operation compared
      with the intraatrial lateral tunnel procedure: early and midterm results.
AB  - BACKGROUND: Arrhythmias are one of the main causes of postoperative morbidity
      superseding Fontan operations. Comparative data on the incidence of sinus node
      dysfunction after the extracardiac Fontan operation (ECFO) and the intraatrial
      lateral tunnel Fontan operation (LTFO) are very limited and controversial. The
      aim of this study was to evaluate whether ECFO decreases the risk of
      postoperative arrhythmias compared with LTFO. METHODS: Seventy-four consecutive
      patients received either an LTFO (n = 29, 5 recordings in 1992 to 9 recordings in
      1997) or an ECFO (n = 45, 11 recordings in 1995 to 5 recordings in 2001). The
      rhythm was documented preoperatively and postoperatively with standard
      electrocardiogram (ECG) recording and ECG monitoring. During follow-up all
      patients had 2-8 (median 3) standard ECG recordings per year. Additionally 45
      patients (65%) had a Holter ECG at least once a year. RESULTS: Median follow-up
      post-ECFO was 4.4 years (1.6-7.2) and post-LTFO it was 7.9 years (5.4-11.1).
      There were 5 early deaths (3 LTFO, 2 ECFO) and 1 late death (LTFO) (total
      mortality 8%). Sinus rhythm persisted in 37 ECFO patients (86%) as compared with
      13 LTFO patients (50%) (p < 0.001). The incidence of new onset supraventricular
      tachyarrhythmias (SVTs) post-ECFO compared with LTFO was lower: 5 patients (11%)
      versus 11 patients (38%) early postoperatively (p < 0.001) and none versus 7
      patients (27%) during follow-up (p < 0.001), respectively. Early postoperatively
      10 LTFO patients (34%) and another 3 patients during follow-up required permanent
      pacemaker implantation due to bradyarrhythmias, but none of the ECFO patients
      required this. CONCLUSIONS: Our data suggest that ECFO decreases the incidence of
      postoperative new onset arrhythmias during early and midterm follow-up compared
      with LTFO.

PMID- 15561015
TI  - Primary repair for aortic arch obstruction associated with ventricular septal
      defect.
AB  - BACKGROUND: The aim of the present study was to evaluate the current outcome and
      reoperation rate after applying a one-stage correction strategy for interrupted
      aortic arch (IAA) with ventricular septal defect (VSD) and also for aortic
      coarctation and hypoplastic aortic arch (CoA-HyAA) with VSD beginning September
      1999. METHODS: Twenty-four consecutive patients with IAA (n = 12) or CoA-HyAA (n
      = 12) with VSD underwent early one-stage correction. Patients' mean age was 12
      days (range, 2 to 188); mean weight was 3.6 kg (range, 2.1 to 7.3), 6 patients
      were less than 2.5 kg. Three IAA were type A, 5 type B1, 3 type B2, and 1 type C.
      Associated anomalies included a large VSD in all, left ventricular outlet tract
      obstruction in 5, transposition of the great arteries, aortopulmonary window,
      persistent truncus arteriosus, and double-outlet right ventricle in 1 patient.
      Selective brain perfusion through innominate artery and selective coronary
      perfusion through aortic root during aortic arch reconstruction was used in all
      patients. Mean follow-up was 2.2 +/- 0.9 years. RESULTS: There was no early, no
      late mortality, and no postoperative neurologic complications. Mean crossclamp
      duration was 72 +/- 32 minutes, lowest temperature 22.8 +/- 4 degrees C and
      selective brain and coronary perfusion duration was 34 +/- 13 minutes. Eighteen
      patients required delayed sternal closure at 1.7 days postoperatively. New
      perioperative management reduced the overall morbidity. Four patients after IAA
      plus VSD repair developed aortic arch restenosis and were successfully treated by
      balloon dilatation. One patient with d-TGA underwent right ventricular outflow
      tract reconstruction of right ventricular outlet tract obstruction 7 months after
      the initial repair. Pressure gradients across the anastomosis at most recent
      follow up were less than 10 mm Hg. All patients are asymptomatic and are
      developing normally. CONCLUSIONS: One-stage complete correction is feasible in
      newborns with aortic arch obstruction with VSD. Complex cardiac anatomy presents
      no additional risk for the procedure. The early one-stage correction yields
      excellent surgical results and good functional outcome.

PMID- 15561017
TI  - Interim mortality in pulmonary atresia with intact ventricular septum.
AB  - BACKGROUND: Recent work has focused attention on interim mortality (death after
      hospital discharge and before second-stage surgery) in hypoplastic left heart
      syndrome. This study investigates interim mortality in infants undergoing
      systemic-to-pulmonary artery shunts for pulmonary atresia with intact ventricular
      septum. METHODS: At two centers in 11 years (January 1991 through December 2001),
      35 infants underwent placement of shunts for palliation of pulmonary atresia with
      intact septum. Patients were identified from the cardiology database at each
      institution, and data were collected retrospectively. The infants were classified
      into two groups, with and without severe right ventricular hypoplasia, based on
      the initial surgical plan (Fontan or two-ventricle repair). RESULTS: The mean age
      and weight of the infants were 9 days and 3.1 kg. The right ventricle was
      severely hypoplastic in 22 of 35 infants. Hospital death occurred in 2 patients
      (9.1%), 1 with severe right ventricular hypoplasia. The remaining 33 patients
      form the study population. There were a total of 5 deaths (15%) after discharge
      and before second-stage operation, all in patients with severe right ventricular
      hypoplasia. Two patients, 1 with hypoplastic right ventricle, died after second
      stage operation. CONCLUSIONS: These data confirm a significant incidence of
      interim death in infants with pulmonary atresia and hypoplastic right ventricle.
      The interim mortality rate in the current two-institution study of infants with
      pulmonary atresia with intact ventricular septum is similar to that in
      hypoplastic left heart syndrome if all patients are considered (15%), and is
      somewhat higher (24%) than that for hypoplastic left heart syndrome if only
      patients with severe right ventricular hypoplasia are considered. This rate of
      interim death must be considered when different treatment options (such as shunt
      or transplant) are contemplated.

PMID- 15561019
TI  - Impaired endothelial function of the umbilical artery after fetal cardiac bypass.
AB  - BACKGROUND: Recently, endothelial dysfunction as a result of fetal cardiac bypass
      has been reported. Here, the effect of fetal cardiac bypass on the endothelial
      function of the umbilical artery was investigated by a tension study. METHODS:
      Fourteen fetal lambs were divided into a control group (n = 7) and a pump group
      (n = 7). In the pump group, cardiac bypass was maintained for 30 minutes using a
      low-volume priming circuit with a centrifugal pump. Hemodynamic measurements and
      blood gas analyses were performed before, during, and 30 and 60 minutes after
      cardiac bypass. The umbilical artery was harvested 60 minutes after cessation of
      cardiac bypass. Endothelium-dependent relaxation (bradykinin, calcium ionophore
      A23187) and endothelium-independent relaxation (sodium nitroprusside) were
      measured after smooth muscle contraction by 60 mmol/L potassium or serotonin and
      compared between the two groups. RESULTS: The umbilical artery flow and aortic
      pressure of the fetus were significantly decreased at 30 and 60 minutes after
      cardiac bypass. Hypoxia and hypercapnia were recognized during and after cardiac
      bypass. Metabolic acidosis progressed during and after cardiac bypass.
      Endothelium-dependent relaxation was impaired in the pump group compared with the
      control group (bradykinin: 43.6% +/- 6.4% in the control group, 18.9% +/- 2.5% in
      the pump group, p < 0.01; A23187: 37.8% +/- 4.6% in the control group, 19.6% +/-
      3.9% in the pump group, p < 0.01). Meanwhile, endothelium-independent relaxation
      was preserved in both groups. CONCLUSIONS: Fetal cardiac bypass caused
      endothelial dysfunction of the umbilical artery and hemodynamic deterioration as
      a result of metabolic acidosis. Prevention of endothelial damage and metabolic
      acidosis could be the main target for successful fetal cardiac surgery.

PMID- 15561021
TI  - The effect of bilateral internal thoracic artery grafting on survival during 20
      postoperative years.
AB  - BACKGROUND: To compare survival of patients receiving bilateral internal thoracic
      artery grafts and single internal thoracic artery grafts more than 20
      postoperative years, assess magnitude of benefit, and identify predictors of
      benefit. METHODS: From cohorts of 8123 patients receiving single internal
      thoracic artery grafts and 2001 receiving bilateral internal thoracic artery
      grafts during primary isolated bypass operations for multivessel coronary disease
      between 1971 and 1989, we identified 1152 propensity-matched pairs. Mean follow
      up of survivors was 16.5 years, with 51 patients followed for 20 years or more.
      Hazard function methodology was used to identify risk factors for mortality,
      compare survival, and assess magnitude of benefit. RESULTS: Comparison of the
      matched pairs showed survival of the bilateral internal thoracic artery and
      single internal thoracic artery groups at 7, 10, 15, and 20 years was 89% versus
      87%, 81% versus 78%, 67% versus 58%, and 50% versus 37%, respectively (p <
      0.0001). Divergence of bilateral internal thoracic artery and single internal
      thoracic artery hazard function curves continued to widen through 20
      postoperative years. At 20 years, bilateral internal thoracic artery grafting was
      predicted to produce worse survival in 2.8% of patients, a survival advantage of
      less than 5% in 12.9%, greater than 10% in 52%, and greater than 15% in 7.6%.
      Combinations of cardiac and noncardiac descriptors were used to define higher and
      lower risk patient subsets. Advanced age, abnormal left ventricular function and
      noncardiac risk factors decreased overall survival but the incremental benefit of
      bilateral internal thoracic artery grafting persisted. CONCLUSIONS: Bilateral
      internal thoracic artery grafting produces improved survival compared with single
      internal thoracic artery grafting during the second postoperative decade, and the
      magnitude of that benefit increases through 20 postoperative years.

PMID- 15561022
TI  - Outcomes after usage of a quality initiative program for off-pump coronary artery
      bypass surgery: a comparison with on-pump surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) may be associated with
      improved outcomes when compared with on-pump coronary artery bypass. This study
      evaluates the use of a system for access and stabilization (SAS) with a coronary
      stabilizer as well as a clinical effectiveness quality initiative (CEQI) process
      regarding outcomes. This included the development of an expanded heart care team
      as well as standardization and refinement of perioperative care at The Lankenau
      Hospital (TLH). Our aim was to evaluate morbidity and mortality of on-pump
      coronary artery bypass grafting (CABG) compared with OPCAB surgery using SAS in
      addition to a CEQI initiative. METHODS: A retrospective consecutive cohort study
      using the Society of Thoracic Surgery (STS) National Database was conducted.
      Three cohorts were analyzed: pre-SAS (December 1, 1999-August 31, 2000); use of
      SAS only (September 1, 2000-April 30, 2001), and the use of SAS + CEQI process
      (May 1, 2001-September 30, 2002). Morbidity and mortality for all on-pump CABG
      procedures performed over the time period of December 1, 1999-September 30, 2002
      were compared with the SAS and SAS + CEQI groups only. RESULTS: One-thousand two
      hundred sixty-seven procedures were performed; 405 on-pump CABGs, 90 OPCABs pre
      SAS, and 772 OPCABs with SAS, of which 552 were in the SAS + CEQI group.
      Statistically mortality was significantly lower in the SAS + CEQI vs the on-pump
      group (0.7% vs 3.0%, p < 0.01). The percentage of patients with prolonged
      ventilation was significantly lower statistically in the SAS + CEQI vs the on
      pump group (4.2% vs 9.7%, p < 0.01). Statistically the length of stay was
      significantly lower in both SAS groups compared with the on-pump group (p <
      0.01). CONCLUSIONS: OPCAB surgery using SAS in conjunction with a CEQI initiative
      improves outcomes for patients compared with on-pump CABG surgery.

PMID- 15561024
TI  - Development of a score to predict the need for coronary artery bypass graft
      surgery in patients with non-ST segment elevation acute coronary syndromes.
AB  - BACKGROUND: Our ability to identify surgical candidates before angiography is
      limited. Early identification of surgical patients would improve preoperative
      management and ultimately postoperative outcomes. The objective of this study was
      to determine whether surgical candidates could be identified before coronary
      angiography using simple clinical variables. METHODS: The study population was
      comprised of 688 patients admitted to a tertiary hospital because of non-ST
      segment elevation acute coronary syndromes. Stepwise logistic regression analysis
      was performed to identify predictors of surgery. A test cohort (50.2%) was used
      to generate the model and a validation cohort (49.8%) was used for independent
      validation of the proposed score. RESULTS: Three variables independently
      predicted the indication for bypass surgery: the absolute thrombolysis in
      myocardial infarction (TIMI) risk score (odds ratio [OR] = 2.34 for each unit
      increase in the score, 95% confidence interval [CI] = 1.89-2.89, p < 0.001), the
      presence of peripheral vascular disease (PVD) (OR = 4.08, CI = 1.48-11.24, p =
      0.006), and the presence of congestive heart failure (CHF) on admission (OR =
      2.57, CI = 1.08-6.81, p = 0.03). A simplified score that spans from 0-10 was
      developed based on the logistic regression model. The score adds two points to
      the TIMI score if PVD is present and one point if CHF is present. The area under
      the receiver-operating-characteristic (ROC) curve of the proposed score for
      predicting surgery was 0.80 +/- 0.02. CONCLUSIONS: The score we have proposed and
      validated can be used to predict the likelihood of bypass surgery before coronary
      angiography and may assist the clinician to tailor preoperative medical therapy.

PMID- 15561026
TI  - Factors associated with presence of ascending aortic atherosclerosis in CABG
      patients.
AB  - BACKGROUND: The indication for epiaortic scanning during coronary artery
      operation is still a matter of debate. Whether this test should be carried out
      selectively or on a routine basis is unclear. The aim of this study was to
      determine factors that predict the presence of atherosclerotic ascending aortic
      wall thickening in patients undergoing coronary artery bypass grafting (CABG).
      METHODS: A total of 500 CABG patients underwent epiaortic scanning using a high
      frequency linear ultrasonic probe. Maximum ascending aortic wall thickness was
      measured and correlated with patient-related variables. RESULTS: Maximum
      ascending aortic wall thickness significantly correlated with age (p < 0.001),
      preoperative creatinine level (p = 0.004), European system for cardiac operative
      risk evaluation (EuroSCORE, p < 0.001), and maximum descending aortic wall
      thickness (p < 0.001). Body mass index and left ventricular ejection fraction
      showed no correlation with maximum ascending aortic wall thickness. Of the
      categorical variables, hypertension (p = 0.02), unstable angina (p = 0.04),
      chronic obstructive pulmonary disease (p = 0.02), cerebrovascular disease (p <
      0.001), and peripheral vascular disease (p < 0.001) were associated with
      increased ascending aortic wall thickness whereas sex, diabetes, acute cases, and
      previous cardiac operation were not. Multivariate analysis revealed maximum
      descending aortic wall thickness (p < 0.001), cerebrovascular disease (p = 0.03),
      and peripheral vascular disease (p = 0.04) as independent variables significantly
      associated with maximum ascending aortic wall thickness. CONCLUSIONS: If
      epiaortic scanning is not carried out routinely for detection of ascending aortic
      arteriosclerosis it should at least be performed in patients with old age,
      hypertension, unstable angina, chronic obstructive pulmonary disease,
      cerebrovascular disease, peripheral vascular disease, elevated creatinine levels,
      higher EuroSCOREs, and increased wall thickness of the descending aorta.

PMID- 15561028
TI  - Early and mid-term outcome of anastomosis of gastroepiploic artery to left
      coronary artery.
AB  - BACKGROUND: The performance of a bypass made to the left coronary artery using
      the gastroepiploic artery was examined. METHODS: Sixty-nine cases of bypass
      operation in which the gastroepiploic artery had been anastomosed to the left
      coronary artery at least 3 years prior were examined. All cases were performed by
      the same surgeon during the period from April 1989 to April 2000. Performance
      immediately after the operation and performance at least 3 years after the
      operation were examined on the basis of graft patency rate. RESULTS: Graft
      patency rates in cases with an anastomosis to the left anterior descending
      coronary artery and cases with an anastomosis to the circumflex artery were
      favorable immediately after the operation, at 96.0% (24 of 25) and 100% (18 of
      18), respectively. However, over the mid-term, the patency rate dropped to 58.8%
      (10 of 17) in cases with an anastomosis to the left anterior descending artery,
      and two cases of cardiogenic sudden deaths occurred during the course of follow
      up. The graft patency rate in cases with an anastomosis to the circumflex artery,
      on the other hand, remained favorable, at 93.3% (14 of 15). In a sequential
      bypass grafting through the right coronary artery, the graft between the left
      anterior descending coronary artery and the right coronary artery was closed, and
      the graft patency rate between the right coronary artery and the circumflex
      artery was 71.4% (10 of 14). CONCLUSIONS: The mid-term patency rate was poor for
      cases in which the gastroepiploic artery had been anastomosed to the left
      anterior descending coronary artery, which suggests that the procedure should be
      avoided. On the other hand, the patency rate was relatively favorable when the
      gastroepiploic artery had been anastomosed to the circumflex artery.

PMID- 15561030
TI  - Concomitant carotid endarterectomy and coronary bypass surgery: outcome of on
      pump and off-pump techniques.
AB  - BACKGROUND: There continues to be a dilemma regarding the best means of surgical
      management of significant carotid artery disease in patients requiring coronary
      artery bypass surgery. A combined approach of coronary artery bypass and carotid
      endarterectomy has shown good results in patients with concomitant carotid and
      coronary artery disease. We reviewed our results of coronary artery surgery using
      conventional cardiopulmonary bypass or off-pump techniques and carotid
      endarterectomy done as a combined procedure. METHODS: Between January 1996 and
      June 2002, 358 patients underwent concomitant coronary artery bypass and carotid
      endarterectomy. There were 140 males (84.3%) and 26 females (15.7%) in group I.
      Group II consisted of 158 males (82.3%) and 34 females (17.7%). One hundred sixty
      six patients (group I) were done off pump whereas in 192 patients (group II), the
      procedure was done using conventional cardiopulmonary bypass. Carotid
      endarterectomy was performed before coronary artery bypass surgery in both
      groups. RESULTS: The average number of grafts were 3.4 +/- 0.8 with average
      operative time of 4.2 +/- 0.4 hours in group I, and 3.3 +/- 0.8 graft with
      operative time of 5.3 +/- 1.2 hours in group II (p = 0.239 and p < 0.001,
      respectively). There were 2 deaths (1.2%) in group I and 3 deaths (1.6%) in group
      II (p = 0.870). No patient from group I and 1 patient (0.5%) from group II had
      postoperative stroke (p = 0.941). Mean hospital stay was 9.0 +/- 1.2 days in
      group I and 11.2 +/- 1.7 days in group II (p < 0.001). At mean follow-up of 2.8
      +/- 0.9 years in group I, 2 patients (1.2%) had late death due to cardiac failure
      and contralateral carotid endarterectomy was done in 2 patients (1.2%). Group II
      had mean follow-up of 2.4 +/- 0.6 years, during which 4 patients (2.1%) had late
      death and contralateral carotid endarterectomy was done in 3 patients (1.6%).
      Late stroke was seen in 1 patient (0.6%) from group I and 2 patients (1.0%) from
      group II. CONCLUSIONS: Concomitant carotid endarterectomy and coronary artery
      bypass is a safe and effective procedure in patients with significant coronary
      and carotid artery disease. Equally good results can be reproduced using
      cardiopulmonary bypass or off-pump techniques for coronary artery surgery, with
      low morbidity, mortality, and good long-term results.

PMID- 15561032
TI  - Off-pump coronary artery bypass grafting in patients with renal dysfunction.
AB  - BACKGROUND: Renal dysfunction is a predictor of increased morbidity and mortality
      after coronary artery bypass grafting, whether it is dialysis-dependent or not.
      Several studies have shown the efficacy of off-pump technique in reducing
      morbidity and mortality in patients with renal dysfunction. However, the actual
      effect of renal dysfunction in off-pump coronary artery bypass grafting has not
      been well understood. METHODS: We conducted a retrospective review of 402
      consecutive patients undergoing off-pump coronary artery bypass grafting from
      April 2001 to June 2003. Sixty-eight patients had chronic renal dysfunction
      (group A); 19 patients were dialysis-dependent; 334 patients had normal renal
      function (group B). Operative variables, morbidity, and mortality were compared
      between the two groups. Furthermore, multivariable analysis was performed to
      identify predictors for short-term survival. RESULTS: Preoperative
      characteristics were similar in the two groups. Blood transfusion rate was higher
      in group A than group B (57.4% and 25.7%, respectively; p < 0.001). In-hospital
      mortality was similar (1.5% and 1.2% in group A and B, respectively; p = 0.853).
      Multivariable analysis revealed that unstable angina, low ejection fraction,
      peripheral vascular disease and redo surgery are significant risk factors for
      poor early result of off-pump coronary artery bypass grafting. CONCLUSIONS: Early
      outcomes of off-pump coronary artery bypass grafting in patients with renal
      dysfunction were comparable to those in patients with normal renal function.
      Renal dysfunction is not a predictor of poor early outcomes after off-pump
      coronary artery bypass grafting.

PMID- 15561033
TI  - Routine use of bilateral skeletonized internal thoracic artery grafts in middle
      aged diabetic patients.
AB  - BACKGROUND: The purpose of this study was to determine whether middle-aged
      diabetic patients aged less than 70 years could have routine use of bilateral
      skeletonized internal thoracic artery grafting without an increased surgical
      risk. METHODS: Between January 1997 and December 2003, 712 consecutive patients
      aged less than 70 years underwent bilateral internal thoracic artery grafting.
      Among these, 164 were diabetic and underwent bilateral internal thoracic artery
      grafting without other preoperative selection than age. The postoperative results
      of these 164 nonselected consecutive diabetic patients were compared to these of
      the 548 nondiabetic patients. RESULTS: The operative mortality rate was 4.3% (7
      patients) in the diabetic group and 2.4% (13 patients) in the nondiabetic group
      (p = not significant [NS]). Deep sternal wound infection was observed in 2
      patients (1.1%) in the diabetic group and in 6 patients (1.2%) in the nondiabetic
      group (p = NS). There were no significant difference in the morbidity rate
      between the two groups except for renal failure without dialysis (6.7% in the
      diabetic group vs 2.0% in the nondiabetic group, p < 0.01). CONCLUSIONS: Routine
      use of bilateral internal thoracic artery grafting was performed in nonselected
      middle-aged diabetic patients without increased morbidity. The low rate of deep
      wound infections could be related to the skeletonized technique of internal
      thoracic artery harvesting.

PMID- 15561034
TI  - Flow in coronary bypass conduits on-pump and off-pump.
AB  - BACKGROUND: The purpose of the study was to measure the blood flow in coronary
      artery bypass grafting conduits on-pump and off-pump and to estimate the total
      conduit flow. METHODS: In a 3.5-year period, 120 patients having coronary artery
      bypass grafting on-pump and 97 patients having coronary artery bypass grafting
      off-pump with the left internal mammary artery anastomosed to the left anterior
      descending artery and saphenous vein grafts to the remaining diseased coronary
      arteries were included in the study. Flow in the bypass conduits was measured
      with the transit-time method. RESULTS: In men the left internal mammary artery
      flow (mean +/- standard error of the mean) was 33.7 +/- 2.0 mL/min on-pump and
      34.4 +/- 2.9 off-pump (p > 0.05). In women the left internal mammary artery flow
      was 29.4 +/- 3.0 mL/min on-pump and 22.8 +/- 1.9 mL/min off-pump (p > 0.05). In
      men the vein graft flow per anastomosis was 30.4 +/- 1.3 mL/min on-pump and 37.8
      +/- 5.4 mL/min off-pump (p > 0.05). In women the vein graft flow per anastomosis
      was 28.0 +/- 2.9 mL/min on-pump and 23.2 +/- 2.9 mL/min off-pump (p > 0.05).
      Consistently in women, the mean conduit flows were numerically lower than in men.
      In patients undergoing coronary artery bypass grafting on-pump the total conduit
      flows (left internal mammary artery plus vein grafts) were 131.4 +/- 2.5 mL/min
      in men and 108.4 +/- 3.2 mL/min in women. CONCLUSIONS: There were no major
      differences in conduit flow on-pump versus off-pump. Conventional coronary artery
      bypass grafting on-pump may restore up to approximately half of the normal
      resting coronary artery blood flow (250 mL/min).

PMID- 15561035
TI  - Hemodynamic changes during posterior vessel off-pump coronary artery bypass:
      comparison between deep pericardial sutures and vacuum-assisted apical suction
      device.
AB  - BACKGROUND: Displacement of the heart to expose posterior vessels during off-pump
      coronary artery bypass may cause hemodynamic derangement. The aims of this study
      were (1) to elucidate the hemodynamic changes during off-pump coronary artery
      bypass for the obtuse marginal branch (OM) of the left circumflex artery; and (2)
      to compare the hemodynamic changes caused by a deep pericardial suture technique
      with those caused by a vacuum-assisted apical suction device for displacement of
      the heart. METHODS: Hemodynamic changes during posterior vessel off-pump coronary
      artery bypass were studied in a prospective randomized manner. A deep pericardial
      suture technique (group 1, n = 10) or a vacuum-assisted apical suction device
      (group 2, n = 10) was used to facilitate the exposure of the OM. Hemodynamic
      variables such as cardiac index, stroke volume index (SVI), mean arterial
      pressure, mean pulmonary artery pressure, central venous pressure, pulmonary
      capillary wedge pressure, heart rate, systemic vascular resistance, pulmonary
      vascular resistance, left ventricular stroke work index, and right ventricular
      stroke work index were monitored during off-pump coronary artery bypass.
      Hemodynamic data were obtained before revascularization of the left anterior
      descending coronary artery at a baseline (T0), 3 minutes after heart displacement
      for revascularization of OM (T1), 3 minutes after the beginning of OM grafting
      (T2), and 3 minutes after the completion of OM grafting and heart repositioning
      (T3). RESULTS: There were no significant differences in the baseline hemodynamic
      variables (T0) between the two groups. In group 1, SVI, cardiac index, left
      ventricular stroke work index, and right ventricular stroke work index decreased
      significantly, and central venous pressure and pulmonary capillary wedge pressure
      increased significantly, during displacement of the heart (T1, p < 0.05). In
      group 2, SVI decreased significantly, and central venous pressure, pulmonary
      capillary wedge pressure, and mean pulmonary artery pressure increased
      significantly during displacement of the heart (T1, p < 0.05). The percent
      changes of cardiac index, SVI, and right ventricular stroke work index during OM
      grafting (T2) in comparison with baseline values (T0) were significantly larger
      in group 1 than in group 2 (cardiac index, 73% +/- 12% versus 90% +/- 11%; SVI,
      69% +/- 12% versus 86% +/- 8%; right ventricular stroke work index, 30% +/- 17%
      versus 71% +/- 25%, in groups 1 versus 2, respectively; p < 0.05). CONCLUSIONS:
      Displacement of the heart using either a deep pericardial suture technique or a
      vacuum-assisted apical suction device caused a significant decrease in SVI. The
      hemodynamic changes during OM grafting were smaller when using a vacuum-assisted
      apical suction device.

PMID- 15561036
TI  - Annular geometry and motion in human ischemic mitral regurgitation: novel
      assessment with three-dimensional echocardiography and computer reconstruction.
AB  - BACKGROUND: Annular geometry and motion in functional ischemic mitral
      regurgitation are incompletely understood. Three-dimensional echocardiography
      demonstrates saddle-shaped annular geometry, but standard methodology does not
      enable quantification of annular motion. Therefore, a novel technique using three
      dimensional echocardiography and computer software was used to characterize
      alterations in mitral annular geometry and motion in patients with ischemic
      mitral regurgitation. METHODS: We developed a computer program to reconstruct the
      mitral annulus based on spatial coordinates from three-dimensional
      echocardiography. Data were obtained at end-diastole and end-systole in 7
      patients with ischemic mitral regurgitation and 5 normal control subjects. Mitral
      annular motion was quantified by calculating the displacement area of the annulus
      between end-diastole and end-systole. RESULTS: Comparison of ischemic mitral
      regurgitation and control patients revealed differences in annular geometry and
      motion at end-diastole. Annular perimeter was greater in ischemic mitral
      regurgitation patients (10.7 +/- 0.7 cm versus 8.6 +/- 0.2 cm in control group; p
      < 0.03), with increased intertrigonal distance in ischemic mitral regurgitation
      patients (2.8 +/- 0.3 cm versus 2.1 +/- 0.1 cm; p < 0.06). These changes resulted
      in increased annular orifice area in ischemic mitral regurgitation patients (9.1
      +/- 1.2 cm2 versus 5.7 +/- 0.3 cm2; p < 0.03). Ischemic mitral regurgitation
      patients had altered annular motion, with reduced movement of the posterior
      annulus (5.4 +/- 0.7 cm2 versus 8.7 +/- 1.1 cm2; p < 0.03). CONCLUSIONS: Computer
      analysis of data obtained from three-dimensional echocardiography demonstrates
      altered annular geometry and motion in patients with ischemic mitral
      regurgitation. Patients with ischemic mitral regurgitation have annular
      dilatation, with an increase in anterior and posterior annular perimeters; this
      is accompanied by an increase in the intertrigonal distance and restriction of
      annular motion.

PMID- 15561038
TI  - Tricuspid valve repair: an old disease, a modern experience.
AB  - BACKGROUND: We review our experience in patients who required surgical correction
      of tricuspid valve disease with concomitant disease of the mitral or aortic
      valve, or both, operated on between 1987 and 1999. METHODS: We studied 232
      consecutive patients (mean age, 59.8 years) followed for a mean of 6.8 years
      (range, 2 to 12 years). All patients were investigated by means of Doppler
      echocardiography, with hemodynamic studies in 135. Median tricuspid insufficiency
      was 3+. The cause was rheumatic heart disease in 186 patients and degenerative in
      46. All patients underwent suture annuloplasty (De Vega or segmental) at the time
      of mitral or aortic valve surgery. Tricuspid lesions were functional in 128
      patients and organic in 104. RESULTS: The hospital and late mortality rates were
      8.1% and 23.3%, respectively. These figures were independent of the type of
      annuloplasty performed. Predictors of hospital mortality were biologic
      prosthesis, renal insufficiency, time of cardiopulmonary bypass, and use of
      inotropic drugs. Predictors of late mortality were age older than 60 years, left
      ventricular ejection fraction less than 0.50, and New York Heart Association
      functional class IV. At 12 years, the actuarial survival rate was 50.5% +/- 6.1%,
      and the actuarial curve free from reoperation 75.7% +/- 7.3%. The actuarial curve
      for freedom from valve-related complication was 39.0% +/- 6.3% at 11 years.
      CONCLUSIONS: Despite the use of modern technologic advances in the diagnosis and
      treatment of valvular hear disease, tricuspid insufficiency continues to be a
      poor prognostic factor in patients with concomitant disease of the mitral or
      aortic valve, or both.

PMID- 15561040
TI  - Long-term results of aortic valve replacement with the St. Jude Toronto stentless
      porcine valve.
AB  - BACKGROUND: Long-term survival and freedom from valve-related events of the St.
      Jude Toronto stentless porcine valve (SPV) are unknown. The aim of this study was
      to investigate late clinical outcomes after aortic valve replacement with the
      Toronto SPV. METHODS: Between 1992 and 2000, 200 patients (131 males, 69 females)
      underwent aortic valve replacement with the Toronto SPV. Mean patient age at
      implantation was 64.6 +/- 10.9 years (range 33 to 82 years). At the time of
      operation, 32%, 51%, and 17% of patients were in New York Heart Association class
      I/II, III, and IV, respectively. Aortic stenosis, aortic insufficiency, and
      combined lesions were present in 64%, 13.5%, and 22.5% of patients
      preoperatively. Concomitant coronary artery bypass grafting was performed in
      34.5% of patients. RESULTS: Perioperative mortality occurred in 2.5% (5/200) of
      patients. There were 31 late deaths. Actuarial survival at 5 and 10 years was
      89.2% and 68.0%, respectively. There was no significant difference in overall
      actuarial survival between isolated valve patients and valve plus coronary artery
      bypass grafting patients, 71% versus 62% respectively, p = 0.85. Actuarial
      freedom from valve reoperation at 5 and 10 years was 97.6% and 79.9%,
      respectively. Actuarial freedom from structural valve deterioration was 98.8% at
      5 years and declined to 77.9% at 10 years. Freedom from structural valve
      deterioration was poorer in patients with preoperative aortic insufficiency or
      bicuspid disease. Actuarial freedom from embolic events and endocarditis at 10
      years were 94.6% and 95.9%, respectively. CONCLUSIONS: Although early clinical
      results were excellent, a significant increase in hazard for structural valve
      deterioration occurred in late follow-up.

PMID- 15561041
TI  - Biomatrix/polymer composite material for heart valve tissue engineering.
AB  - BACKGROUND: Decellularized extracellular matrix has been suggested as a scaffold
      for heart valve tissue engineering or direct implantation. However, cell removal
      impairs the physical properties of the valve structure and exposes bare collagen
      fibers that are highly thrombogenic. Matrix/polymer hybrid valves with improved
      biological and mechanical characteristics may be advantageous. METHODS: Porcine
      aortic valves were decellularized enzymatically and impregnated with
      biodegradable poly(hydroxybutyrate) by a stepwise solvent exchange process.
      Biocompatibility was tested in vitro using cell proliferation and coagulation
      assays. Proinflammatory activity was assessed in vivo by implantation of
      matrix/polymer patches in the rabbit aorta. Biomechanic valve properties and
      fluid dynamics were tested in a pressure/flow-controlled pulse duplicating
      system. Matrix/polymer hybrid valves were implanted in pulmonary and aortic
      position in sheep. RESULTS: Biocompatibility assays indicated that human blood
      vessel cells survive and proliferate on matrix/polymer hybrid tissue. In vitro
      activation of cellular and plasmatic coagulation cascades was lower than with
      uncoated control tissue. After implantation in the rabbit aorta, matrix/polymer
      hybrid patches healed well, with complete endothelialization, mild leukocyte
      infiltration, and less calcification than control tissue. Matrix/polymer hybrid
      tissue had superior tensile strength and suture retention strength, and hybrid
      valves showed good fluid dynamic performance. The two valves in aortic position
      performed well, with complete endothelialization and limited inflammatory cell
      invasion after 12 weeks. Of the two valves in pulmonary position, one failed.
      CONCLUSIONS: Matrix/polymer hybrid tissue valves have good biological and
      biomechanic characteristics and may provide superior replacement valves.

PMID- 15561042
TI  - Umbilical cord blood derived endothelial progenitor cells for tissue engineering
      of vascular grafts.
AB  - BACKGROUND: A substantial limitation regarding present pediatric cardiac surgery
      is the lack of appropriate materials for the repair of congenital defects. To
      address this shortcoming, tissue engineering is a scientific field that aims at
      in vitro fabrication of living autologous grafts with the capacity of growth,
      repair, and regeneration. Here we focused on tissue engineered vascular grafts
      using human umbilical cord blood derived endothelial progenitor cells (EPCs), as
      a noninvasive cell source for pediatric applications. METHODS: EPCs were isolated
      from 20 ml fresh human umbilical cord blood by Ficoll gradient centrifugation and
      cultured in endothelial basal medium containing growth factors. After
      proliferation and differentiation cells were analyzed by immunohistochemistry and
      seeded onto three-dimensional (3D) biodegradable vascular scaffolds (porosity >
      95%, n = 22). Twenty-four hours after seeding the vascular grafts were positioned
      into a pulse-duplicator-in vitro system and grown for 48 hours under biomimetic
      conditions. A second group was grown 6 days statically and an additional 6 days
      biomimetically. Controls were cultured statically. Analysis of the grafts
      included immunohistochemistry, histology, and scanning electron microscopy.
      RESULTS: Preseeding differentiated EPCs indicated constant endothelial phenotypes
      including acetylated low-density lipoprotein, cluster of differentiation 31, von
      Willebrand factor, and endothelial nitric oxide synthetase. Seeded EPCs
      established favorable cell-to-polymer attachment and proliferation into the 3D
      tubular scaffolds. Both conditioned and static cellular constructs demonstrated
      positive staining for cluster of differentiation 31, von Willebrand factor, and
      expression of endothelial nitric oxide synthase. CONCLUSIONS: Human umbilical
      cord derived EPCs indicated exceptional growth characteristics used for tissue
      engineering of vascular grafts. These cells demonstrated a constant endothelial
      phenotype and related functional features. Based on these results EPCs seem to be
      a promising autologous cell source with regard to cardiovascular tissue
      engineering, particularly for the repair of congenital defects.

PMID- 15561043
TI  - Aortic dissection after previous cardiovascular surgery.
AB  - BACKGROUND: Risk of repairing aortic dissection after previous cardiovascular
      surgery has not been described clearly. This study assesses early and late
      outcomes of such reoperations. METHODS: From January 1, 1990, to January 1, 2002,
      108 patients with prior cardiovascular surgery (isolated coronary artery bypass
      grafting, 51%; isolated valve surgery, 21%; aortic aneurysm repair, 24%; and
      combinations of these in the remainder) underwent reoperation for aortic
      dissection (emergency operation for acute dissection in 24%). Mean age was 63 +/-
      13 years, and 85% were men. The interval since prior surgery ranged from 10 days
      to 22 years (median, 3.8 years). This was the third operation for 8%. Ascending
      aortic repair with or without aortic arch or descending aortic repair was
      performed in 40%, aortic valve replacement (n = 15) or repair (n = 17) with
      ascending aortic repair in 30%, aortic root replacement with or without aortic
      arch or descending aortic repair in 30%, and aortic arch with or without
      descending aortic repair in 1%. Circulatory arrest was used in 78%, with
      retrograde brain perfusion in 58%. RESULTS: Hospital mortality was 6%, stroke 4%,
      renal failure 2%, and respiratory failure 7%. Survival at 30 days and 1, 3, 5,
      and 7 years was 93%, 85%, 74%, 63%, and 53%, respectively. Aortic reoperation was
      performed in 7 patients, with freedom from this event at 30 days and 1, 3, 5, and
      7 years of 98%, 95%, 93%, 91%, and 89%., respectively CONCLUSIONS: Aortic
      dissection after cardiovascular surgery is rare and can be managed with
      acceptable operative risks and good long-term survival. Need for subsequent
      aortic reoperation is uncommon.

PMID- 15561045
TI  - Increased tissue microarray matrix metalloproteinase expression favors
      proteolysis in thoracic aortic aneurysms and dissections.
AB  - BACKGROUND: Little information is available regarding the role of matrix
      metalloproteinases (MMPs) in thoracic aortic aneurysms and dissections. We
      applied tissue microarray analysis to determine MMP profiles in a large group of
      surgically resected thoracic aneurysms and dissections. METHODS: Specimens from
      47 patients undergoing a variety of surgical procedures for thoracic aneurysm (n
      = 30) and dissection (n = 17) were included. Expression of MMP-1, MMP-2, and MMP
      9 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were assessed
      by aortic tissue microarray immunostaining. Matrix metalloproteinase and TIMP
      expression in aortic tissue was compared with seven control aortic specimens,
      free of any vascular disease. RESULTS: Expression of MMP-1 and MMP-9 was
      significantly increased in aneurysm and aortic dissection patients compared with
      control specimens (p < 0.05). Expression of TIMP-2 was significantly increased in
      the entire patient group, compared with control specimens (p < 0.05). Aortic
      dissection patients had higher MMP-2 and MMP-9 expression than aortic aneurysm
      patients in areas of disease. Compared with control patients, the MMP-9 to TIMP-1
      ratio (a relative index of proteolytic state) was increased in both the aortic
      aneurysm and dissection groups (p < 0.05). CONCLUSIONS: The increased MMP
      expression in aortic aneurysms and dissections indicates a metamorphosis in the
      aneurysm wall toward increased proteolysis compared with the normal aorta.
      Furthermore, we find even higher MMP-2 and MMP-9 presence in aortic dissection.
      In both aneurysms and dissections, this transformation to a proteolytic state
      likely plays an important pathophysiologic role in the development and
      progression of the aortic disease. The recognition of this pathophysiologic
      mechanism raises the potential for drug therapy to interrupt the cascade of
      events.

PMID- 15561047
TI  - Long-term outcome of type B aortic intramural hematoma: comparison with classic
      aortic dissection treated by the same therapeutic strategy.
AB  - BACKGROUND: The long-term clinical course and therapeutic strategy of patients
      with type B aortic intramural hematoma (IMH) are not completely known. The
      purpose of this study was to clarify long-term prognosis of patients with type B
      IMH by comparison with type B classic aortic dissection (AD). METHODS: Clinical
      data were compared retrospectively between 37 patients with acute type B IMH (IMH
      group) and 69 patients with acute type B AD (AD group). Our therapeutic strategy
      for all patients was medical therapy with frequent follow-up imaging studies and
      timed surgical repair in cases with progression. RESULTS: Initially, medical
      therapy was selected for 104 of 106 (98%) patients. In two patients of the AD
      group, immediate surgical treatment was performed because of aortic rupture. As
      for complications, no significant difference was seen between the two groups.
      There was no significant difference in the incidence of the total number of
      deaths; early death, late death, or causes of deaths. The actuarial survival
      rates for the IMH group at 1, 2, 5, and 10 years were 97 +/- 3, 97 +/- 3, 85 +/-
      9, and 85 +/- 9%, respectively; the values were 96 +/- 1, 96 +/- 1, 89 +/- 4, and
      71 +/- 9%, for the AD group. The actuarial survival rates of the two groups were
      not significantly different from each other (p = 0.398). CONCLUSIONS: Patients
      with type B IMH have similar long-term prognosis to patients with type B AD.
      Medical therapy with frequent follow-up imaging studies and timed surgical repair
      in cases with progression can be a rational therapeutic strategy in patients with
      type B IMH.

PMID- 15561048
TI  - Septal myectomy results in regression of left ventricular hypertrophy in patients
      with hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized
      by ventricular hypertrophy that occurs in the absence of predisposing
      cardiovascular stimuli; approximately one quarter of patients with HCM will have
      left ventricular (LV) outflow tract obstruction. Transaortic septal myectomy
      relieves outflow gradients and improves symptoms, but the effect of operation on
      ventricular hypertrophy is not well defined. METHODS: We reviewed 60 patients who
      underwent septal myectomy for obstructive HCM; all had complete two-dimensional
      and Doppler studies including calculation of LV mass and LV mass index before
      operation and after dismissal. RESULTS: Before myectomy the mean LV outflow
      gradient was 67 +/- 44 mm Hg, and at dismissal the mean LV outflow gradient was
      12 +/- 13 mm Hg (p < 0.004). We found a significant decrease in the LV mass and
      LV mass index that occurred early after operation and persisted beyond 2 years
      follow-up. The early decrease in LV mass was greatest in patients younger than 50
      years, but patients of all ages benefited from extended septal myectomy with
      decrease in LV hypertrophy. CONCLUSIONS: Transaortic septal myectomy results in
      significant decreases in LV mass and LV mass index. This favorable remodeling
      occurs early after operation and persists beyond 2 years. Whether the regression
      of LV mass continues to decrease or stabilize over time is unclear.

PMID- 15561049
TI  - Left ventricular assist device performance with long-term circulatory support:
      lessons from the REMATCH trial.
AB  - BACKGROUND: Left ventricular assist device (LVAD) failure and malfunction rates
      are critical gauges for establishing LVADs as a long-term therapy for end-stage
      heart failure patients. These device performance measures, however, have been
      inadequately characterized in the bridge-to-transplantation literature. METHODS:
      REMATCH is a randomized trial that compares optimal medical management with LVAD
      implantation for patients with end-stage heart failure. An independent committee
      adjudicated patient outcomes. The primary endpoint--survival--was analyzed by
      intention to treat using the log-rank statistic. Frequency of event occurrence
      was analyzed by Poisson regression. The time to first event was analyzed by the
      product limit method. Device performance was disaggregated into confirmed
      malfunctions and system failures. The latter were events in which patients could
      not be rescued with backup circulatory support measures. RESULTS: The 1-year
      survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients
      versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate
      was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for
      medical patients. System failure was 0.13 per patient per year and the confirmed
      LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year
      and 37% at 2 years. CONCLUSIONS: Despite the observed rates of device malfunction
      and replacement, LVAD implantation confers clinically significant improvement
      with regard to survival as compared with medical management. Device modifications
      and innovations for infection management exhibit great promise of improving
      device performance in the near future.

PMID- 15561050
TI  - A closed perfusion system with heparin coating and centrifugal pump improves
      cardiopulmonary bypass biocompatibility in elderly patients.
AB  - BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory and hemostatic
      activation, which may contribute to postoperative complications. Our aim was to
      compare the inflammatory response, coagulation, and fibrinolytic activation
      between two different perfusion systems: one theoretically more biocompatible
      with a closed-circuit, complete heparin coating, and a centrifugal pump, and one
      conventional system with uncoated circuit, roller pump, and a hard-shell venous
      reservoir. METHODS: Forty-one elderly patients (mean age, 73 +/- 1 years, 66%
      men) undergoing coronary artery bypass grafting or aortic valve replacement were
      included in a prospective, randomized study. Plasma concentrations of complement
      factors (C3a, C4d, Bb, and sC5b-9), proinflammatory cytokines (tumor necrosis
      factor-alpha, interleukin-6, and interleukin-8), granulocyte degradation products
      (polymorphonuclear elastase), and markers of coagulation (thrombin-antithrombin)
      and fibrinolysis (D-dimer, tissue plasminogen activator antigen and tissue
      plasminogen activator-plasminogen activator inhibitor-1 complex) were measured
      preoperatively, at bypass during rewarming (35 degrees C), 60 minutes after
      bypass, and on day 1 after surgery. RESULTS: The mean concentrations of C3a (
      39%; p = 0.008), Bb (-38%; p < 0.001), sC5b-9 (-70%; p < 0.001), interleukin-8 (
      60%; p = 0.009), polymorphonuclear-elastase (-55%; p < 0.003), and tissue
      plasminogen activator antigen (-51%; p = 0.012) were all significantly lower in
      the biocompatible group during rewarming. Sixty minutes after bypass, the mean
      concentrations of sC5b-9 (-39%; p = 0.006) and polymorphonuclear-elastase (-55%;
      p < 0.001) were lower in the biocompatible group. CONCLUSIONS: The results
      suggest that a closed perfusion system with a heparin-coated circuit and a
      centrifugal pump may improve cardiopulmonary bypass biocompatibility in elderly
      cardiac surgery patients in comparison with a conventional system.

PMID- 15561052
TI  - A prospective randomized study to evaluate the effect of leukodepletion on the
      rate of alveolar production of exhaled nitric oxide during cardiopulmonary
      bypass.
AB  - BACKGROUND: Cardiopulmonary bypass is associated with a whole body inflammatory
      reaction. Exhaled nitric oxide increases in inflammatory lung conditions (eg,
      asthma) in proportion to the severity of inflammation, and has been proposed as a
      marker of pulmonary inflammation during cardiopulmonary bypass. This study
      evaluated the effect of arterial line leukocyte depletion during cardiopulmonary
      bypass on the rate of alveolar production of exhaled nitric oxide. METHODS: One
      hundred and ten patients with normal respiratory function, undergoing first time
      coronary artery bypass grafting, were randomized to two groups. Fifty-five
      patients had an arterial line leukocyte-depleting filter and 55 controls had a
      standard arterial line filter. Nitric oxide was sampled through an endotracheal
      Teflon tube after median sternotomy, but before cardiopulmonary bypass and 30
      minutes after cardiopulmonary bypass, using a real time chemiluminescence
      analyzer, during the phase of the alveolar plateau. RESULTS: There were no
      significant differences in the precardiopulmonary bypass values of exhaled nitric
      oxide between the control (2.92 +/- 1.51 ppb/s) and the leukodepletion group
      (3.11 +/- 1.53 ppb/s) (p = 0.4). After cardiopulmonary bypass, the rate of
      alveolar production of exhaled nitric oxide increased in both groups, being,
      however, significantly higher in the control group (4.68 +/- 1.89 vs 3.72 +/-
      1.33 ppb/s) (p = 0.02). CONCLUSIONS: Continuous arterial line leukocyte-depletion
      significantly reduces the rate of alveolar production of exhaled nitric oxide
      after cardiopulmonary bypass. Changes in the rate of alveolar production of
      exhaled nitric oxide may be used as a marker of pulmonary inflammation in
      coronary artery surgery.

PMID- 15561053
TI  - Method and value of digital recording of operations for congenital heart disease.
AB  - PURPOSE: We describe the methods we have used to employ digital video techniques
      in the teaching of surgery for congenital heart disease. DESCRIPTION: This paper
      describes the hardware and software required to initiate and utilize digital
      video in surgery for congenital heart defects. Images are collected through a
      headlight camera and stored on standard digital-video camera tape. Tapes are
      catalogued using a purpose built database, linked to the hospital data system,
      and employing the European Pediatric Codes coding system for diagnostic and
      procedural coding. This permits keyword as well as patient-based searches. Master
      tapes are then digitally edited using proprietary software to create for example
      teaching tapes or to explain the operation to the family of the patient.
      EVALUATION: Eighty percent of the procedures performed by one surgeon (M.J.E.)
      during the last year have been recorded in this way. CONCLUSIONS: A working
      digital archive of pediatric cardiac surgical procedures has been created.
      Database links to hospital systems create the opportunity for linking full,
      visual records of procedures to be retained in an electronic patient record.

PMID- 15561055
TI  - Replacement of the aortic valve and ascending aorta with an extended root
      stentless xenograft.
AB  - PURPOSE: We present an early series to determine the technical feasibility of
      simultaneous aortic valve and complete ascending aortic replacement using a
      longer stentless aortic xenograft, harvested with an extended root. DESCRIPTION:
      The stentless xenograft valved conduits commercially available are too short for
      complete ascending aorta replacement, and usually a prosthetic tube graft is
      required distally. EVALUATION: To avoid this extra prosthetic conduit distally a
      number of stentless aortic xenografts with extended conduit were obtained from a
      supplier (Medtronic Inc). They were inserted in 6 elderly patients (67.8 +/- 7.1
      years) who all required aortic valve and ascending aorta replacements owing to
      pathologic dilation. CONCLUSIONS: In all cases an extra prosthetic conduit was
      avoided, and the length of the available biological conduit comfortably allowed
      total ascending aortic replacement without tension. The advantages therefore were
      one less suture line, cost saving regarding the prosthetic conduit, shorter cross
      clamping time, and possibly shorter time spent on hemostasis.

PMID- 15561057
TI  - Metachronous and synchronous lung tumors: five malignant lung pathologies in 1
      patient during 7 years.
AB  - We present the case of a 70-year-old man who previously had a left upper
      lobectomy for nonsmall cell lung carcinoma that subsequently developed into small
      cell carcinoma, which was successfully treated, and finally he had a right upper
      lobectomy that revealed three synchronous lung malignancies. We were unable to
      find a previous case report with a total of five separate lung malignancies with
      a combination of metachronous and synchronous tumors. This case demonstrates the
      importance of screening after the diagnosis and treatment of lung carcinoma.

PMID- 15561058
TI  - Successful removal of bovine pericardium by bronchoscope after lung volume
      reduction surgery.
AB  - We report on a patient in whom, 10 months after lung volume reduction surgery,
      bovine material visibly migrated to the bronchial lumen. In this particular case,
      bronchoscopic treatment was successful. The patient remained well 12 months after
      such treatment. The report also suggests that the alternative use of absorbable
      material will reduce later postoperative complications.

PMID- 15561059
TI  - Combined blunt aortic and bronchial injury.
AB  - We report the case of a 29-year-old man with left blunt chest trauma resulting in
      an intimal tear of the proximal descending aorta, for which he underwent
      successful thoracic endovascular graft stenting. He subsequently developed
      progressive left lung collapse, and bronchoscopy revealed left bronchial
      disruption. A left thoracotomy with end-to-end anastomosis of the left bronchus
      was performed successfully. The literature from 6 other similar cases of
      concomitant aortic and bronchial injuries was reviewed.

PMID- 15561060
TI  - Acute postoperative shingles after thoracic sympathectomy for hyperhidrosis.
AB  - Shingles secondary to reactivation of a previous varicella-zoster virus infection
      has been reported to develop within surgical wounds and after trauma. We report
      the case of a 17-year-old girl with history of chicken pox in childhood who had
      acute postoperative shingles develop along the T3-T4 dermatomes after thoracic
      sympathectomy for hyperhidrosis. The possible causes and precipitating factors
      are discussed.

PMID- 15561061
TI  - Anterior mediastinal presentation of a giant angiomyolipoma.
AB  - Angiomyolipomas are benign, solitary, noninvasive lesions that most often arise
      in the kidney. Extrarenal manifestations of these tumors include the skin,
      oropharynx, the abdominal wall, retroperitoneum, gastrointestinal tract, heart,
      lung, liver, uterus, penis, and spinal cord. We report a patient with a giant
      angiomyolipoma located in the anterior mediastinum. We believe this is the
      seventh reported case of mediastinal angiomyolipoma and the largest reported by
      size. It is the second reported lesion to arise in the anterior mediastinum.
      Distinction from other pulmonary or thoracic masses relies on the appreciation of
      the unique and characteristic histologic features of these mediastinal
      angiomyolipomas. We conclude that, although rare, angiomyolipoma should be
      considered in the differential diagnosis of a mediastinal tumor.

PMID- 15561062
TI  - Leiomyoma of an accessory tracheal bronchus.
AB  - We present a rare case of leiomyoma arising in an accessory right bronchus in a
      55-year-old man who had been treated for bronchial asthma. Diagnosis was
      established on the results of bronchoscopic biopsy. An emergency operation was
      performed because the patient had begun to complain of severe dyspnea. The tumor
      was completely removed by electrocautery with a wire snare by rigid bronchoscopy.
      Postoperative bronchoscopic findings revealed a tracheal bronchus arising above
      the carina, and the root of the tumor existed in the orifice of the branch. Final
      histology revealed a leiomyoma.

PMID- 15561063
TI  - Video-assisted bronchial stump reinforcement with an intercostal muscle flap.
AB  - For lobectomy patients at considerable risk of developing a postoperative
      bronchopleural fistula, the bronchial stump reinforcement with an intercostal
      muscle flap is sometimes performed. This procedure usually requires a standard
      thoracotomy, even if video-assisted thoracoscopic surgery (VATS) is better for
      the patient. Our patient was a 76-year-old male with lung cancer and severe
      diabetes mellitus. He underwent lobectomy and systematic nodal dissection
      combined with bronchial stump reinforcement using an intercostal muscle flap,
      performed as a VATS procedure. No postoperative complications were observed. This
      procedure is applicable to patients who are candidates for VATS lobectomy.

PMID- 15561064
TI  - Cardiopulmonary bypass with bivalirudin in type II heparin-induced
      thrombocytopenia.
AB  - Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia
      poses significant challenges. Inadequate pharmacokinetic profiles, monitoring,
      reversibility, and availability often limit alternative anticoagulation
      strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently
      approved for use in patients undergoing percutaneous coronary interventions. Its
      unique properties, including a relatively short half-life, an anticoagulation
      effect that closely correlates with activated clotting time, and an alternate
      metabolic pathway for elimination, make bivalirudin an attractive agent for
      cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia.
      We report our experience using bivalirudin in 2 patients undergoing coronary
      artery bypass grafting.

PMID- 15561065
TI  - Coronary ostial stenosis after aortic valve replacement, revisited.
AB  - Coronary artery occlusive disease that develops after an uncomplicated aortic
      valve replacement is well recognized. We present a case that required two further
      coronary operations and two salvage angioplasty procedures for a continuing
      fibrotic process in the ascending aorta. The literature and pathology are
      reviewed.

PMID- 15561066
TI  - Mitral valve aneurysm with infective endocarditis.
AB  - A case of mitral valve aneurysm associated with infective endocarditis is
      reported. Two-dimensional echocardiography revealed a saccular structure in the
      anterior leaflet that bulged into the left atrium throughout the cardiac cycle.
      During operation, the vegetation on the commissure of the right and left aortic
      leaflet and a 3-mm perforation on the noncoronary leaflet were found. The mitral
      valve and aortic valve were replaced with mechanical prosthesis. Pathology of the
      excised valves showed inflammation. For this patient, we considered that the
      infected aortic regurgitant jet striking the ventricular surface of the anterior
      mitral leaflet could be the mechanism of the leaflet aneurysm.

PMID- 15561067
TI  - Aorto-right atrial fistula caused by type A aortic dissection.
AB  - We present a rare surgical case of aorto-right atrial fistula caused by type A
      aortic dissection in an 85-year-old man. Complaints included progressive general
      fatigue and anorexia caused by right side heart failure. However, there were no
      symptoms attributable to onset of the aortic dissection. A diagnosis of aorto
      right atrial fistula was made from intraoperative transesophageal
      echocardiography. Total aortic arch replacement concomitant with direct closure
      of the fistula was performed successfully.

PMID- 15561068
TI  - Ischemic esophageal necrosis secondary to traumatic aortic transection.
AB  - Esophageal necrosis with perforation secondary to traumatic aortic transection is
      extremely rare but usually fatal. A 47-year-old man complained of sudden
      swallowing difficulty 6 days after blunt trauma. Computed tomography showed a
      ruptured aorta and the midesophagus shifted to the right side with luminal
      obliteration because of the ruptured aorta. After primary repair of the partially
      transected aorta, unexpected mediastinitis because of esophageal perforation was
      noted. Upper endoscopy showed midesophageal ulceration, necrosis, and
      perforation. Biopsy samples were consistent with ischemia. The possibility of
      direct esophageal trauma or intraoperative esophageal injury was ruled out.
      Esophageal exclusion with thoracoscopic decortication and multiple antibiotics
      were ineffective, and the patient eventually died. Ischemic esophageal necrosis
      caused by mechanical compression can occur in a traumatic aortic transection.
      Dysphagia, when present with radiologic signs, indicates a displaced and
      compressed esophagus. In spite of aggressive surgical and medical treatment for a
      perforated esophagus, the prognosis remains poor.

PMID- 15561069
TI  - Long-term survival with acquired ventricular septal defect after myocardial
      infarction.
AB  - Acquired ventricular septal defects (VSD) are rare and devastating complications
      after myocardial infarction. The long-term prognosis with medical therapy is
      extremely poor. We report on a patient who developed progressive heart failure
      within 3 months after myocardial infarction due to an unknown VSD. The left
      ventricular function was severely impaired. After diagnosing VSD by
      echocardiography, surgical occlusion was performed. In addition, a biventricular
      pacemaker was applied using epicardial leads. The patient recovered almost
      completely 6 weeks postoperative. Beside hemodynamic changes, biventricular
      pacing is potentially sufficient to improve the postoperative outcome of patients
      with severe heart failure in these conditions.

PMID- 15561070
TI  - Double intramural coronary arteries in D-transposition of the great arteries.
AB  - We report a rare case of D-transposition of the great arteries with intramural
      origin of both the left and right coronary arteries. The patient underwent a
      successful arterial switch operation at 7 days of life with an uneventful
      postoperative course. Regardless of challenging coronary anatomy, the arterial
      switch operation remains the optimal approach for repair of the transposition of
      the great arteries in the neonate.

PMID- 15561071
TI  - Direct aortic interposition of anomalous left anterior descending coronary artery
      without cardiopulmonary bypass.
AB  - An anomalous origin of the left anterior descending (LAD) coronary artery arising
      from the pulmonary artery is a congenital malformation rarely described in
      adults. We describe the case of a 42-year-old man with this malformation who
      underwent an interposition of the LAD coronary artery to the ascending aorta with
      an off-pump technique. The clinical presentation, angiographic findings, and
      surgical treatment are discussed.

PMID- 15561072
TI  - Three-dimensional demonstration of total anomalous pulmonary venous return with
      contrast-enhanced magnetic resonance angiography.
AB  - A newborn male was hospitalized for a heart murmur and severe cyanosis after his
      birth. Echocardiography showed an abnormal vein crossing below the diaphragm;
      total anomalous pulmonary venous return (TAPVR, Darling type III) was suspected.
      A contrast-enhanced 3-dimensional magnetic resonance angiography (MRA) was
      performed on the 6th day after his birth to assess pulmonary vein stenosis. The
      MRA was obtained with a 1.5-T superconducting imager (Signa Horizon LX EchoSpeed,
      with 8.3 operating system software; GE Medical Systems, Milwaukee, WI) and a 4
      channel phased array coil for the brain to optimize signal detection with the
      image sequence from a fast-spoiled gradient-echo (fast-SPGR) with fat
      suppression. Contrast medium (gadopentetate dimeglumine, 0.1 mmol/kg, Magnevist,
      Schering, Berlin, Germany), 0.6 mL, was administered at 0.2 mL/sec using a power
      injector.

PMID- 15561073
TI  - Ruptured left coronary sinus of valsalva aneurysm into the left ventricle.

PMID- 15561074
TI  - Fixation of silicone stents in the subglottic trachea: preventing stent migration
      using a fixation apparatus.
AB  - Silicone stents are widely used to treat benign or malignant airway stenosis.
      However, since straight silicone stents placed into the subglottic trachea to
      treat stenosis display a high risk of migration, novel approaches are required.
      The present report outlines our method of external fixation for silicone stents
      in the subglottic trachea. This technique utilizes a fixation apparatus, is
      readily performed, and may help to overcome the hesitation seen in placing
      silicone stents for subglottic tracheal stenosis.

PMID- 15561075
TI  - Minimizing foreign material in the reconstruction of infected complex
      annuloaortic disruption.
AB  - For repairing disrupted ventriculoaortic continuity caused by complicated aortic
      root infection, my colleagues and I simply approximate it without any patch
      material to decrease the possible risk of recurrence of infection. After massive
      and aggressive debridement of the infected tissue, all discontinuities or abscess
      cavities were excluded by using interrupted sutures to anchor a new valve
      substitute in 13 patients. Only 1 patient died of uncontrolled sepsis. During the
      follow-up period (mean, 21.5 months) all 12 survivors have done well, without any
      evidence of paravalvular leakage or recurrent infections.

PMID- 15561076
TI  - Improvement of coronary artery fistula surgery by intraoperative imaging.
AB  - Complete surgical closure of coronary artery fistulas may be difficult because of
      complex anatomy and often multiple sites of origin. This study therefore assessed
      whether intraoperative fistula imaging would contribute to and improve the final
      surgical result. Seven adult patients underwent operation for coronary
      arteriovenous fistula during a 10-year period. In all 4 patients who had image
      guidance, the operation was guided by immediate imaging to achieve complete and
      persistent closure. In contrast, 2 of 3 patients who underwent operation without
      image guidance had residual left-to-right shunts at follow-up. Image guidance was
      helpful and increased the success rate of surgical closure of coronary artery
      fistulas.

PMID- 15561077
TI  - Distal aortic perfusion during aortic arch reconstruction: another tool for the
      aortic surgeon.
AB  - Complex aortic arch reconstruction remains one of the greatest challenges facing
      cardiothoracic surgeons today. Deep hypothermic circulatory arrest is the most
      common technique for open arch replacement. Either antegrade or retrograde
      cerebral perfusion is often utilized in an attempt to decrease neurologic
      complications. In addition to cerebral perfusion, we have employed continuous
      perfusion of the thoracic aorta to minimize spinal cord, visceral, and lower
      extremity ischemia. This approach does not significantly increase the complexity
      of the operative procedure while reducing the ischemic time of critical areas,
      which may lead to improved patient outcomes.

PMID- 15561078
TI  - Percutaneous valve replacement: current state and future prospects.
AB  - Percutaneous valve implantation is the development of a foldable heart valve that
      can be mounted on an expandable stent delivered percutaneously through standard
      catheter-based techniques and implanted within a diseased valve annulus. In cases
      with severe aortic stenosis, the diseased valve has to be pre-dilated. To perform
      a true replacement the diseased valve has to be ablated and removed. In this
      article, we review the development of percutaneous valve replacement technology
      and discuss future prospects in this field.

PMID- 15561080
TI  - Time to move beyond retrospective analyses for thymic neoplasms and conduct a
      prospective multi-institutional clinical trial.

PMID- 15561082
TI  - Argatroban as a heparin substitute in cases of heparin-induced thrombocytopenia.

PMID- 15561083
TI  - Neurological dysfunction in elderly patients undergoing coronary artery bypass
      operation.

PMID- 15561084
TI  - Fenestration in extracardiac-conduit Fontan operation.

PMID- 15561086
TI  - Interatrial septal defect at lowest part of the septum.

PMID- 15561089
TI  - Additional uses of stabilization devices in cardiac surgery.

PMID- 15561090
TI  - Delayed paraplegia after thoracic and thoracoabdominal aneurysm repair: timing of
      reinsertion of spinal drain.

PMID- 15561091
TI  - Alternative mitral valve ring.

PMID- 15561093
TI  - Annulus sizing in aortic remodeling procedure.

PMID- 15561096
TI  - Connexin43 synthesis, phosphorylation, and degradation in regulation of transient
      inhibition of gap junction intercellular communication by the phorbol ester TPA
      in rat liver epithelial cells.
AB  - The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces transient
      inhibition of gap junction intercellular communication (GJIC) in several cell
      types. The initial block in GJIC has been attributed to protein kinase C (PKC)
      mediated phosphorylation of connexin gap junction proteins, including connexin43
      (Cx43). Restoration of GJIC, associated with normalization of the Cx43
      phosphorylation status, has been ascribed to different events, including
      dephosphorylation of Cx43 and de novo synthesis of Cx43 or other, non-gap
      junctional, proteins. The data presented suggest that restoration of GJIC during
      continuous TPA exposure in normal and transformed rat liver epithelial cells is
      dependent on synthesis of Cx43 protein, as well as the transport of already
      synthesized Cx43 from intracellular pools to the plasma membrane. Reactivation of
      inactivated Cx43 by dephosphorylation does not appear to be involved in the
      recovery of GJIC. Both PKC and MAP kinase is involved in TPA-induced degradation
      of Cx43 and inhibition of GJIC. We show that coincubation of TPA with the protein
      synthesis inhibitor cycloheximide or the transcription inhibitor actinomycin D
      results in synergistic enhancement of the level of activated ERK1/2. Together,
      the present data highlight Cx43 degradation and synthesis as critical
      determinants in TPA-induced modifications of cell-cell communication via gap
      junctions.

PMID- 15561097
TI  - The use of non-physiological conditions to isolate fetal cells from maternal
      blood.
AB  - Fetal cells are always present in maternal blood starting in the first trimester
      of pregnancy, however a rapid, simple, and consistent procedure for their
      isolation for prenatal non-invasive genetic investigation is still lacking.
      Sensitivity and recovery of fetal cells is jeopardized by the minute amount of
      circulating fetal cells and their loss during the enrichment procedure. We report
      here a single-step approach to isolate fetal cells from maternal blood which
      relies on the use of non-physiological conditions to modify cell densities before
      their separation in a density gradient and in a newly developed cell separation
      device. Isolated fetal cells have been investigated using cytochemistry, Soret
      band absorption microscopy, monoclonal antibodies for epsilon- and gamma-chain
      Hb, monoclonal antibody for i-antigen, and by fluorescence in situ hybridization
      (FISH). Fetal cells were always detected in all 105 maternal blood samples
      investigated and fetal aneuploidies were correctly diagnosed by FISH, in a pilot
      study of pathological pregnancies, in fetal cells isolated from maternal blood
      obtained either before or after invasive procedure.

PMID- 15561098
TI  - Differential impact of diverse anticancer chemotherapeutics on the Cdc25A
      degradation checkpoint pathway.
AB  - When exposed to DNA-damaging insults such as ionizing radiation (IR) or
      ultraviolet light (UV), mammalian cells activate checkpoint pathways to halt cell
      cycle progression or induce cell death. Here we examined the ability of five
      commonly used anticancer drugs with different mechanisms of action to activate
      the Chk1/Chk2-Cdc25A-CDK2/cyclin E cell cycle checkpoint pathway, previously
      shown to be induced by IR or UV. Whereas exposure of human cells to topoisomerase
      inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h)
      activation of the pathway including degradation of the Cdc25A phosphatase and
      inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this
      checkpoint even after a prolonged treatment. Unexpectedly, although the
      alkylating agent cisplatin also induced degradation of Cdc25A (albeit delayed,
      after 8-12 h), cyclin E/CDK2 activity was elevated and DNA synthesis continued, a
      phenomena that correlated with increased E2F1 protein levels and consequently
      enhanced expression of cyclin E. These results reveal a differential impact of
      various classes of anticancer chemotherapeutics on the Cdc25A-degradation
      pathway, and indicate that the kinetics of checkpoint induction, and the relative
      balance of key components within the DNA damage response network may dictate
      whether the treated cells arrest their cell cycle progression.

PMID- 15561099
TI  - CAPON expression in skeletal muscle is regulated by position, repair, NOS
      activity, and dystrophy.
AB  - In skeletal muscle, the localization of nNOS is destabilized in the absence of
      dystrophin, which impacts muscle function and satellite cell activation. In
      neurons, the adaptor protein, carboxy-terminal PDZ ligand of nNOS (CAPON),
      regulates the distribution of neuronal nitric oxide synthase (nNOS), which
      produces the key signaling molecule nitric oxide (NO). While a CAPON-like gene is
      known to compensate functionally for a dystrophic phenotype in muscle of
      Caenorhabditis elegans, CAPON expression has not been reported for mammalian
      muscle. Here, CAPON expression was identified in mouse muscle using Northern and
      Western blotting and in situ hybridization in combination with immunostaining for
      laminin. CAPON RNA was expressed in developing normal and dystrophic muscles near
      fiber junctions with tendons, and levels increased from 1 to 3 weeks. In
      regenerating normal muscle and also in dystrophic muscles in the mdx mouse, CAPON
      transcripts were prominent in satellite cells and new myotubes. Expression of
      CAPON RNA increased in diaphragm muscle of normal and mdx mice after treatment
      with L-arginine, the NOS substrate. Both CAPON and utrophin protein levels
      increased in dystrophic quadriceps muscle after treatment with the steroid
      deflazacort plus L-arginine, known to reduce the dystrophic phenotype. The
      identification of CAPON transcripts and protein in mammalian muscle and responses
      to L-arginine suggest CAPON may have a functional role in stabilizing neuronal
      NOS in skeletal muscle in the cytoskeletal complex associated with
      dystrophin/utrophin, with possible applications to therapy for human muscular
      dystrophy.

PMID- 15561100
TI  - Nuclear RNAs confined to a reticular compartment between chromosome territories.
AB  - RNA polymerase II transcripts are confined to nuclear compartments. A detailed
      analysis of the nuclear topology of RNA from individual genes was performed for
      transcripts from the marker gene coding for chloramphenicol acetyltransferase,
      expressed at a high level from the HTLV-1 LTR promoter. The construct was
      transfected into A293 cells where the RNA was organized as an extensive reticular
      network. We also studied the RNA distribution from combinations of neighboring
      HIV and bacterial resistance genes that co-integrated within the genome of COS-7
      cells-revealing spherical or track-like accumulations of RNA that were
      extensively branched. There were many nuclei with distinct but overlapping RNA
      accumulations. Since the coding genes localized at the overlapping points, the
      RNAs are synthesized at a common region and diverge. The correlation between the
      frequency of the separation of the transcripts and the physical distance of the
      respective genes suggests a subcompartmentalization in the microenvironment of
      genes on the basis of geometric parameters. Thus, the more distant the genes are
      on the same chromosome, the more likely they are confined to separated
      subcompartments of an extensive reticular system. Co-delineation of the RNA
      transcripts with Cajal bodies and chromosome territories indicated the
      organization of nuclear RNA transcripts in a reticular interchromosome domain
      compartment.

PMID- 15561101
TI  - Galig, a novel cell death gene that encodes a mitochondrial protein promoting
      cytochrome c release.
AB  - Galectin-3 internal gene (Galig) was recently identified as an internal gene
      transcribed from the second intron of the human galectin-3 gene that is
      implicated in cell growth, cell differentiation, and cancer development. In this
      study, we show that galig expression causes morphological alterations in human
      cells, such as cell shrinkage, cytoplasm vacuolization, nuclei condensation, and
      ultimately cell death. These alterations were associated with extramitochondrial
      release of cytochrome c, a known cell death effector. Furthermore, Bcl-xL co
      transfection significantly reduced the release of cytochrome c induced by galig
      expression, suggesting a common pathway between the cytotoxic activity of galig
      and the anti-apoptotic activity of Bcl-xL. This antagonism was not observed upon
      co-transfection of Bcl-2 and galig. Galig encodes a mitochondrial-targeted
      protein named mitogaligin. Structure-activity relationship studies showed that
      the mitochondrial addressing of mitogaligin relies on an internal sequence that
      is required and sufficient for the release of cytochrome c and cell death upon
      cell transfection. Moreover, incubation of isolated mitochondria with peptides
      derived from mitogaligin induces cytochrome c release. Altogether, these results
      show that galig is a novel cell death gene encoding mitogaligin, a protein
      promoting cytochrome c release upon direct interaction with the mitochondria.

PMID- 15561102
TI  - Repressed E-cadherin expression in the lower crypt of human small intestine: a
      cell marker of functional relevance.
AB  - In epithelia, abnormal expression of E-cadherin is related to pathologies
      involving a loss of cell polarization and/or differentiation. However, recent
      observations suggest that E-cadherin could also be repressed under physiological
      conditions, such as in some epithelial stem cell lineages. In the present work,
      we have analyzed E-cadherin expression in human intestinal epithelial cell
      progenitors and investigated its potential role. E-cadherin expression was
      analyzed along the crypt-villus axis by immunofluorescence on cryosections of
      small intestine. E-cadherin was found to be differentially expressed, being
      significantly weaker in the cells located at the bottom of the crypts.
      Surprisingly, neither the E-cadherin protein nor transcript were detected in a
      normal human intestinal epithelial (HIEC) crypt cell model isolated in our
      laboratory, whereas other E-cadherin-related components such as catenins and APC
      were present. Forced expression of E-cadherin in HIEC cells increased membrane
      associated beta-catenin and was accompanied by the appearance of junction-like
      structures at the cell-cell interface. Functionally, cell kinetics and p21Cip
      levels were found to be altered in the E-cadherin expressing HIEC cells as
      compared to controls. Furthermore, a significant reduction of the migration
      abilities and an increase in sensitivity to anoikis were also observed. These
      results suggest that down-regulated expression of E-cadherin is a human
      intestinal crypt base cell-related feature that appears to be of functional
      relevance for the maintenance of the progenitor cell population.

PMID- 15561103
TI  - Proteasomes are tightly associated to myofibrils in mature skeletal muscle.
AB  - Proteasomes are the major actors of nonlysosomal cytoplasmic protein degradation.
      In particular, these large protein complexes (about 2500 kDa) are considered to
      be responsible for muscular degradation during skeletal muscle atrophy. Despite
      their unusual and important size, they are widely described as soluble and mobile
      in the cytoplasm. In mature skeletal muscle, we have previously observed a
      sarcomeric distribution of proteasomes, as revealed by the distribution of
      alpha1/p27K, a subunit of the 20S core-particle (prosome) of proteasome. Here, we
      extend these observations at the electron microscopic level in vivo. We also show
      that this sarcomeric pattern is dependent of the extension of the sarcomere.
      Using isolated myofibrils, we demonstrate that proteasomes are still attached to
      the myofibrils after the isolation procedure, and reproduce the observations made
      in vivo. In addition, the extraction of actin by gelsolin largely removes
      proteasomes from isolated myofibrils, but some of them are held in place after
      this extraction, showing a sarcomeric disposition in the absence of any
      detectable actin, and suggesting the existence of another molecular partner for
      these interactions. From these results, we conclude that most of detectable 20S
      proteasomes in skeletal muscle cells is tightly attached to the myofibrils.

PMID- 15561104
TI  - When, where and how the bridge breaks: anaphase bridge breakage plays a crucial
      role in gene amplification and HSR generation.
AB  - Amplified genes are frequently localized on extrachromosomal double minutes (DMs)
      or in chromosomal homogeneously staining regions (HSRs). We previously showed
      that a plasmid bearing a mammalian replication initiation region could
      efficiently generate DMs and HSRs after transfection into human tumor cell lines.
      The Breakage-Fusion-Bridge (BFB) cycle model, a classical model that explains how
      HSRs form, could also be used to explain how the transfected plasmids generate
      HSRs. The BFB cycle model involves anaphase bridge formation due to the presence
      of dicentric chromosomes, followed by the breakage of the bridge. In this study,
      we used our plasmid-based model system to analyze how anaphase bridges break
      during mitosis. Dual-color fluorescence in situ hybridization analyses revealed
      that anaphase bridges were most frequently severed in their middle irrespective
      of their lengths, which suggests that a structurally fragile site exists in the
      middle of the anaphase bridge. Breakage of the chromosomal bridges occurred prior
      to nuclear membrane reformation and the completion of cytokinesis, which
      indicates that mechanical tension rather than cytokinesis is primarily
      responsible for severing anaphase bridges. Time-lapse observation of living cells
      revealed that the bridges rapidly shrink after being severed. If HSR length was
      extended too far, the bridge could no longer be resolved and became tangled
      depending on the tension. The unbroken bridge appeared to inhibit the completion
      of cytokinesis. These observations strongly suggest that anaphase bridges are
      highly elastic and that the length of the spindle axis determines the maximal HSR
      length.

PMID- 15561105
TI  - The cyclooxygenase inhibitor indomethacin modulates gene expression and represses
      the extracellular matrix protein laminin gamma1 in human glioblastoma cells.
AB  - The induction of cyclooxygenase-2 (COX-2) expression is associated with more
      aggressive gliomas and poor survival. Nonsteroidal anti-inflammatory drugs
      (NSAIDs) inhibit COX activity and have antitumorigenic properties. In this
      report, our initial aim was to determine if indomethacin would alter gene
      expression as measured by suppression subtractive hybridization (SSH). Three up
      regulated and four down-regulated genes by indomethacin treatment were
      identified. Laminin gamma1, an extracellular matrix molecule, was the most
      significantly repressed gene. The repression of laminin gamma1 by indomethacin
      was confirmed by Northern and Western blot analyses and occurred in a
      concentration- and time-dependent manner at the protein level. Among several
      NSAIDs tested, only sulindac sulfide and indomethacin suppressed laminin gamma1
      protein expression, and this repression was observed in both COX-expressing and 
      deficient cell lines, suggesting that laminin gamma1 repression by COX inhibitors
      was independent of COX. Indomethacin, at a concentration that represses laminin
      gamma1, inhibited glioblastoma cell invasion that was partially restored with
      additional human laminin protein containing gamma1 chain. The repression of
      laminin gamma1 by NSAIDs may be related to attenuation of invasion of brain
      tumors. These findings are important in understanding the chemopreventive
      activity of some NSAIDs and could be relevant for designing therapeutic
      strategies against glioblastoma.

PMID- 15561106
TI  - The proto-oncogene Fgr regulates cell migration and this requires its plasma
      membrane localization.
AB  - Fgr participates in integrin signaling in myeloid leukocytes. To examine the role
      of its specific domains in regulating cell migration, we expressed various Fgr
      molecules in COS-7 cells. Full-length, membrane-bound Fgr, but not an N-terminal
      truncation mutant that distributed to an intracellular compartment, increased
      cell migration on fibronectin and enhanced phosphorylation of the p85 subunit of
      phosphatidylinositol 3-kinase (PI3K), cortactin and focal adhesion kinase (FAK)
      at Y397 and Y576. Fgr increased Rac GTP loading, and phosphorylation of the Rac
      GEF Vav2, and bound to a protein complex formed by the Rho inhibitor p190RhoGAP
      and FAK, increasing p190RhoGAP phosphorylation, in a manner absolutely dependent
      on membrane localization. A kinase-defective truncation mutant of Fgr increased
      cell migration, albeit to a much lower extent than full-length Fgr, and was found
      to associate with the plasma membrane, to activate Rac and to form complexes with
      p190RhoGAP/FAK. Formation of complexes between p190RhoGAP, Fgr, and the FAK
      related protein Pyk2 were also detected in murine macrophages. These findings
      suggest that the proto-oncogene Fgr regulates cell migration impinging on a
      signaling pathway implicating FAK/Pyk2 and leading to activation of Rac and the
      Rho inhibitor p190RhoGAP.

PMID- 15561107
TI  - Common and cell type-specific responses of human cells to mitochondrial
      dysfunction.
AB  - In yeast, mitochondrial dysfunction activates a specific pathway, termed
      retrograde regulation, which alters the expression of specific nuclear genes and
      results in increased replicative life span. In mammalian cells, the specific
      nuclear genes induced in response to loss of mitochondrial function are less well
      defined. This study characterizes responses in nuclear gene expression to loss of
      mitochondrial DNA sequences in three different human cell types: T143B, an
      osteosarcoma-derived cell line; ARPE19, a retinal pigment epithelium cell line;
      and GMO6225, a fibroblast cell population from an individual with Kearns-Sayre
      syndrome (KSS). Quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) was used to measure gene expression of a selection of
      glycolysis, TCA cycle, mitochondrial, peroxisomal, extracellular matrix, stress
      response, and regulatory genes. Gene expression changes that were common to all
      three cell types included up-regulation of GCK (glucokinase), CS (citrate
      synthase), HOX1 (heme oxygenase 1), CKMT2 (mitochondrial creatine kinase 2), MYC
      (v-myc myelocytomatosis viral oncogene homolog), and WRN (Werner syndrome
      helicase), and down-regulation of FBP1 (fructose-1, 6-bisphosphatase 1) and
      COL4A1 (collagen, type IV, alpha 1). RNA interference experiments show that
      induction of MYC is important in rho0 cells for the up-regulation of glycolysis.
      In addition, a variety of cell type-specific gene changes was detected and most
      likely depended upon the differentiated functions of the individual cell types.
      These expression changes may help explain the response of different tissues to
      the loss of mitochondrial function due to aging or disease.

PMID- 15561108
TI  - Distinct roles of EGF repeats for the Notch signaling system.
AB  - Notch is a single-pass transmembrane receptor that mediates cell fate choice in
      various species and developmental contexts. The Notch signal is transduced by its
      intracellular domain, which acts as a transcriptional activator, and is released
      from the plasma membrane by proteolytic cleavages. This process is initiated by
      intercellular association of the epidermal growth factor (EGF) repeats between
      Notch and the DSL (Delta, Serrate, Lag-2) ligands but the detailed mechanism is
      yet to be clarified. Here we demonstrate that Notch1 can form homodimers, which
      is achieved by its EGF motifs. The Notch1 dimer formation increased in response
      to ligand presentation and HES1 promoter was stimulated, implying that receptor
      homodimerization is an important initial step in Notch signal transduction. EGF
      motifs also serve as a protection against proteases, including TNF-alpha
      converting enzyme, which prevents Notch1 from ligand-independent activation.
      Multiple functions of the Notch EGF motifs, such as the prevention of
      constitutive activation, reciprocal interaction with the ligands and lateral
      interaction for homodimerization, appear to constitute crucial elements of the
      Notch signaling system.

PMID- 15561109
TI  - Growth factors.

PMID- 15561110
TI  - Acute compartment syndrome of the limb.
AB  - In this review the aetiology, clinical signs, diagnosis and therapy of the acute
      compartment syndrome of the limb is discussed. It is a limb- and untreated life
      threatening emergency. For good results, early detection is necessary. It is
      important to educate those taking care of patients of risk, especially in the
      early symptoms and signs. In uncooperative, unconscious and sedated patients
      pressure monitoring is recommended. The critical level of the absolute
      intracompartmental pressure is unclear. It is recommended to use a delta p
      pressure of 30 mm Hg. Below this pressure in the presence of clinical signs a
      fasciotomy of all compartments is the treatment of choice.

PMID- 15561111
TI  - Trauma in rural Kenya.
AB  - BACKGROUND: Trauma in Africa is an increasingly significant problem. The aims of
      this study were to document the epidemiology and clinical management of trauma in
      a rural Kenyan hospital and from this to highlight important areas for the
      medical training of doctors managing trauma in similar situations. METHODS:
      Prospective audit of 202 consecutive trauma patients admitted to Kijabe Hospital.
      RESULTS: The mean patient age was 31, 77% were males. The median Injury Severity
      Score (ISS) was nine. The median distance to hospital was 60 km, with a 9 h delay
      in presentation. Injury mechanisms included road traffic accidents 52%, fall 22%,
      assaults 13% and burns 6%. The main injuries were limb fractures, soft tissue
      injuries, head injury and haemo/pneumothorax. Common interventions included
      fracture management, wound debridement, chest drain insertion, blood transfusion
      and skin grafting. The overall mortality rate was 3.5%. CONCLUSION: With
      appropriate resources and training, good trauma outcomes are possible. The
      importance of access to hospital care and orthopaedic training are highlighted.

PMID- 15561112
TI  - Animal-related injury in an urban New Zealand population.
AB  - The contribution of animals to injury in urban populations is not well described.
      We reviewed our trauma admissions for animal-related injury to identify animals
      involved, risk factors and patterns of injury. Eight thousand nine hundred and
      fifty-four patients were admitted for trauma during the study period. One hundred
      and sixty-seven injuries were due to animals (1.9%). Horses were involved in 86%
      and dogs in 10% of injuries. Most horse riders were injured in falls. Factors
      associated with increased risk included being young, female and riding for
      leisure. Body regions most commonly injured were the head and both upper and
      lower extremities. Patterns of injury were identified. Horse-related injury is a
      significant source of traumatic injury in an identifiable at-risk subgroup of our
      urban population. High rates of head injury and low rates of helmet use suggest a
      more effective strategy to encourage use of protective headgear is needed.
      Further efforts aimed at injury prevention must include an improvement in skill
      and knowledge of horsemanship, particularly in the at-risk group of young female
      amateur riders. Mechanistic patterns of injury and body-region markers identified
      in this study may assist early recognition of severe and occult injuries in these
      patients.

PMID- 15561113
TI  - Population-based prediction of trauma volumes at a Level 1 trauma centre.
AB  - OBJECTIVE: With an ageing US population, the demographics of traumatic injuries
      are being significantly altered. Census projections predict that the number of
      Americans over age 65 will double in the next 20 years. We used stochastic
      methods to forecast trauma admissions in order to predict the effects of such
      demographic changes at our trauma centre. METHODS: Age- and sex-related rates of
      traumatic admission were determined using population statistics and trauma
      registry data from 1994 to 1999. These rates were then projected from 2000 to
      2025 based on both the Lee-Carter and random walk with drift methods. Stochastic
      population projections were made and paired with the projected trauma rates,
      allowing estimation of total trauma volume. RESULTS: Trauma rates were predicted
      to increase for most age groups. Trauma admissions are predicted to increase 57%
      by 2024. By 2019, 50% of trauma admissions will be 60 or older. CONCLUSIONS: Our
      trauma volume is expected to increase 57% by 2024, an increase of 2% per year.
      More of this volume will consist of elderly patients, potentially requiring
      increased health-care resources.

PMID- 15561114
TI  - A corrective osteotomy for post-traumatic malrotation and shortening of the
      femur.
AB  - Malrotation following femoral nailing is problematic. We describe a new one-stage
      technique which utilises three components; a cortico-periosteal sleeve, a
      "dialled-in"correction of rotation and a peg-shaped osteotomy. Seven patients
      were treated. The mean correction of malrotation was within 5 degrees of the
      normal side and the mean correction of length was within 8 mm of the normal side.
      Clinical union was achieved on average by 6 months (range 4-8 months). The only
      complication was locking screw breakage in one case. The cortico-periosteal
      sleeve avoids the need for bone graft, surgery is facilitated by the use of
      "dialled-in" correction of rotation and a peg to correct length.

PMID- 15561115
TI  - Technique and considerations when using external fixation as a standard treatment
      of femoral fractures in children.
AB  - Femoral fractures in children can be treated effectively and with a low
      complication rate by using external fixation. However, as with most treatment
      modalities there is a learning curve to be considered. The aim of this paper is
      to report "tricks" and different considerations that we have learned to be of
      value based on experience gained during a prospective and consecutive study of 98
      femoral fractures in children aged 3-15 years. Our experience is based on the use
      of a unilateral fixator with the option to apply axial dynamisation. Traction
      prior to operation is not needed if the child is operated on within 24h. During
      surgery a traction table will prevent significant malrotation and facilitate
      reduction prior to insertion of the pins. Four 4 or 5mm pins are sufficient for
      adequate stability in children. Transverse skin incisions are preferable for pin
      insertion as the scars become smaller and the soft tissue irritation during
      activity is less when compared with longitudinal incisions. Unrestricted weight
      bearing can be allowed. A nihilistic approach to pin site care with daily showers
      is as effective as more aggressive treatment with local antiseptics. Pin
      infections can occur but are mild and can be treated locally or with a short
      period of antibiotics taken orally. Pin-loosening and deep infections are very
      uncommon. By using external fixation, malunion, overgrowth or delayed union can
      almost be avoided completely. Re-fractures are rare and occur only after
      significant trauma. Treatment time is relatively short. No physiotherapy or
      further protection of the leg is necessary during or after healing.

PMID- 15561116
TI  - Evaluation of the long intra-medullary hip screw.
AB  - There have been many publications about second generation femoral nails, such as
      the Russell-Taylor nail (Smith & Nephew Richards, Memphis, TN, USA) and Long
      Gamma Nail (Howmedica, Rutherford, NJ, USA), but little work has been published
      on the Long Intra-medullary Hip Screw (IMHS, Smith & Nephew). We set out to
      evaluate the effectiveness of the Long IMHS as a device for the fixation of
      proximal femoral fractures. We retrospectively reviewed 30 patients who had a
      Long IMHS inserted for a sub-trochanteric or proximal femoral fracture. Of the 30
      patients, three had died and six were lost to follow up, leaving 21, whom we
      reviewed. Of the 21 patients reviewed the mean age was 67 years and the mean
      follow up was 31 weeks. Mean time to union was 15.65 weeks, with one non-union.
      There were three superficial wound infections. In one patient there was loosening
      of the distal locking screws, requiring removal and there was one case of intra
      operative femoral shaft fracture. We conclude that, the Long IMHS is an effective
      device for the treatment of sub-trochanteric and proximal femoral fractures with
      a high rate of union achieved and a low complication rate.

PMID- 15561117
TI  - Compensation for rotational malalignment after intramedullary nailing for femoral
      shaft fractures. An analysis by plantar pressure measurements during gait.
AB  - INTRODUCTION: Even though rotational malalignment due to a femoral shaft fracture
      leads to clinical complaints, a large number of patients may have none of
      significance. The ability to compensate may play a role. The purpose of this
      study is to give insight into aspects of compensatory gait of patients with a
      femoral malrotation and the relation with clinical complaints. METHODS: In a
      cross-sectional laboratory setting, foot-progression angles (FPA) during gait
      were measured using a foot scan device. Results were related to CT determined
      femoral torsion and clinical complaints. RESULTS: Patients with external (EMR) or
      internal malrotation (IMR) showed differences in foot-progression angles
      (DeltaFPA) in the same direction of their malrotation. Compared to IMR patients,
      EMR patients appeared to compensate less for their malrotation. No statistically
      significant differences were detected between these groups for absolute and
      relative compensation. EMR patients scored worse at the Oxford 12-item and WOMAC
      score and experienced more problems executing demanding activities than do
      patients without malrotation. Correlations were found between Oxford 12-item and
      WOMAC score and relative compensation. CONCLUSIONS: Femoral torsion and the FPA
      are strongly related. All patients compensate towards normal values of FPA at
      their fractured side. Patients who are less able to compensate have more physical
      complaints. EMR patients tend to have more complaints and difficulty
      compensating.

PMID- 15561118
TI  - Comparison of autogenous and allogenous posterior cruciate ligament
      reconstructions of the knee.
AB  - This prospective clinical study was performed to compare the functional results
      and clinical outcomes of 32 autogenous and 23 allogenous posterior cruciate
      ligament (PCL) reconstructions with an average follow-up of 34 months. Both
      groups showed similar age, gender and follow-up time. The indications for surgery
      included knees with functional disability due to pain and instability from high
      energy PCL injury with failure of conservative treatments. Arthroscopic single
      bundle PCL reconstruction was performed with a similar technique in both groups
      with the exception of graft selection. All patients received the same
      postoperative rehabilitation. The evaluation parameters included functional
      assessment, ligament laxity, functional score, kinematics evaluation and
      radiographic examination. Autogenous and allogenous PCL reconstructions showed
      comparable functional results and clinical outcomes. No statistically significant
      difference was noted in ligament laxity and radiographic changes between the two
      groups. Complications were more prevalent with autogenous grafts. In conclusion,
      autogenous and allogenous tendon grafts are equally effective in PCL
      reconstruction.

PMID- 15561119
TI  - Osteochondral autografts transfer for post-traumatic osteochondral defect of the
      knee-2 to 5 years follow-up.
AB  - The treatment of post-traumatic osteochondral defects of the weight-bearing
      surface of the knee in young active patients remains a significant challenge. We
      report the results of an osteochondral autograft transfer (OAT) in 18 patients
      (mean age 29 years) with post-traumatic focal osteochondral defects of the knee.
      Sixteen lesions were over the femoral condyle and two were over the tibial
      plateau. The average size of the lesion was 4.1 cm(2) (from 2.25 to 6 cm(2)), and
      the subchondral bone involved no more than 1 cm in depth. Osteochondral grafts
      were harvested from the non-weight-bearing area of the femoral condyle. Ten
      patients also had concomitant surgical procedures. The average follow-up was 42
      months (from 24 to 64 months). All patients were evaluated by Lysholm and Tegner
      activity scores and plain radiographs. Nine patients had MRI, eight patients had
      second-look arthroscopy and two had a biopsy. Sixteen patients (89%) had good to
      excellent results, while two patients with lesion over the tibial surface had
      fair results. The biopsy revealed survival of hyaline cartilage. For small to
      medium osteochondral lesion over the femoral condyle of the knee in selected
      patients, osteochondral autografting yielded promising short to mid-term results.

PMID- 15561120
TI  - Arthroscopic single- versus double-bundle posterior cruciate ligament
      reconstructions using hamstring autograft.
AB  - This prospective study compared the clinical results of single- and double-bundle
      posterior cruciate ligament (PCL) reconstruction with a minimum follow-up of 2
      years. There were 35 patients including 19 single- and 16 double-bundle posterior
      cruciate ligament reconstructions using hamstring autograft. The average age was
      29.4 +/- 13.6 years versus 28.2 +/- 10.4 years; and the average follow-up was
      41.0 +/- 13.1 months versus 28.1 +/- 4.2 months for single- and double-bundle
      reconstruction, respectively. The indication for surgery was functional
      disability of the knee due to pain and instability as the result of high-energy
      PCL injury. The evaluation parameters included functional assessment, ligament
      laxity, functional score and radiographs of the knee. The results showed no
      significant difference in functional assessment, ligament laxity, functional
      score and radiographic changes of the knee between the two techniques. The rate
      of overall satisfaction with the operation was comparable from patient and
      surgeon perspectives. Contrary to many recent reports, the results of this study
      showed that single- and double-bundle PCL reconstruction using hamstring
      autograft produced comparable clinical results in medium-term follow-up. The
      difference between single- and double-bundle PCL reconstruction, if any, can be
      concluded only with long-term results and larger number of patients.

PMID- 15561121
TI  - Delayed development of complete heart block after a blunt chest trauma.

PMID- 15561122
TI  - Pneumonitis following grease gun injury.
AB  - Grease gun trauma often involves subcutaneous injection of the grease because of
      the high pressures required for its industrial application. The case is presented
      of a man who developed a pneumonitis shortly after sustaining a grease gun
      injury, with injection of grease into his upper thigh associated with significant
      vascular damage. Pneumonitis has not previously been reported with this type of
      injury, and is likely to represent a systemic reaction to the local inflammatory
      response. Management of these injuries should incorporate early debridement with
      anticipation of underlying vascular trauma, and also an awareness of the
      potential systemic complications.

PMID- 15561123
TI  - Delayed presentation of superior mesenteric artery rupture following blunt
      trauma.

PMID- 15561124
TI  - Delayed displacement of a paediatric atlas fracture through the synchondrosis
      after minor trauma.

PMID- 15561125
TI  - Zone III sacral fractures--two case reports.

PMID- 15561126
TI  - The pen is mightier than the sword.

PMID- 15561127
TI  - Regeneration of a segmental bone defect after acute osteomyelitis due to an
      animal bite.

PMID- 15561128
TI  - "Failure" of forearm intramedullary elastic nails.
AB  - Elastic nails are an established modality for treating forearm fractures in
      children. These nails are usually removed 6-9 months after surgery as refracture
      may occur in 10% of cases if the nails removed earlier. We report a case of
      refracture of the forearm bones with elastic nails in situ, 5 months after the
      original fractures. The fracture was angulated approximately 80 degrees with the
      apex pointing anteriorly. Closed reduction was difficult and resulted in breakage
      of the ulnar nail. The authors describe the details and outline the management of
      this unreported complication.

PMID- 15561129
TI  - Extraction of the broken intramedullary femoral nail--an innovative technique.

PMID- 15561130
TI  - Broken guide wire with intrapelvic protrusion: a technique for removal.

PMID- 15561131
TI  - A case of osteomyelitis following flexible nailing of a femoral shaft fracture in
      an 11 years old.

PMID- 15561132
TI  - Fixed flexion deformity of the knee following femoral physeal fracture: the
      Inverted Cyclops lesion.
AB  - An adolescent inter-condylar fracture of the distal femur was treated with
      percutaneous cancellous screws and an above-knee plaster. The subsequent fixed
      flexion deformity of the knee was initially considered to be due to soft tissue
      capsular scarring and adhesions but arthroscopic assessment of the joint
      identified an "Inverted Cyclops" lesion. This consisted of excess callus and
      fibrous tissue arising from the femoral notch. Arthroscopic excision of this
      tissue cured the deformity.

PMID- 15561133
TI  - Fracture of the proximal tibia following Elmslie-Trillat osteotomy: a report of
      two cases.

PMID- 15561134
TI  - Applying the Kapandji technique for a distal tibial fracture in a 15 year old.

PMID- 15561135
TI  - Fracture of the posterior process of talus.
AB  - Fracture of posterior process of talus is quite rare, but is associated with
      significant morbidity as it involves two articular surfaces. We report two such
      cases in which open reduction and internal fixation were done with good
      functional results. One of the cases had a concomitant medial malleolus fracture
      which to the best of our knowledge has not been reported so far.

PMID- 15561136
TI  - Divergent anticodon recognition in contrasting glutamyl-tRNA synthetases.
AB  - The pathogenic bacterium Helicobacter pylori utilizes two essential glutamyl-tRNA
      synthetases (GluRS1 and GluRS2). These two enzymes are closely related in
      evolution and yet they aminoacylate contrasting tRNAs. GluRS1 is a canonical
      discriminating GluRS (D-GluRS) that biosynthesizes Glu-tRNA(Glu) and cannot make
      Glu-tRNA(Gln). In contrast, GluRS2 is non-canonical as it is only essential for
      the production of misacylated Glu-tRNA(Gln). The co-existence and evident
      divergence of these two enzymes was capitalized upon to directly examine how
      GluRS2 acquired tRNA(Gln) specificity. One key feature that distinguishes
      tRNA(Glu) from tRNA(Gln) is the third position in the anticodon of each tRNA (C36
      versus G36, respectively). By comparing sequence alignments of different GluRSs,
      including GluRS1s and GluRS2s, to the crystal structure of the Thermus
      thermophilus D-GluRS:tRNA(Glu) complex, a divergent pattern of conservation in
      enzymes that aminoacylate tRNA(Glu)versus those specific for tRNA(Gln) emerged
      and was experimentally validated. In particular, when an arginine conserved in
      discriminating GluRSs and GluRS1s was inserted into Hp GluRS2 (Glu334Arg GluRS2),
      the catalytic efficiency of the mutant enzyme (k(cat)/K(Mapp)) was reduced by
      approximately one order of magnitude towards tRNA(Gln). However, this mutation
      did not introduce activity towards tRNA(Glu). In contrast, disruption of a
      glycine that is conserved in all GluRS2s but not in other GluRSs (Gly417Thr
      GluRS2) generated a mutant GluRS2 with weak activity towards tRNA(Glu1). Synergy
      between these two mutations was observed in the double mutant
      (Glu334Arg/Gly417Thr GluRS2), which specifically and more robustly aminoacylates
      tRNA(Glu1) instead of tRNA(Gln). As GluRS1 and GluRS2 are related by an apparent
      gene duplication event, these results demonstrate that we can experimentally map
      critical evolutionary events in the emergence of new tRNA specificities.

PMID- 15561137
TI  - Crystal structure of mouse triggering receptor expressed on myeloid cells 1 (TREM
      1) at 1.76 A.
AB  - Triggering receptor expressed on myeloid cells (TREM) 1 is an activating receptor
      expressed on myeloid cells whose ligand(s) remain elusive. TREM-1 stimulation
      activates neutrophils and monocytes and induces the secretion of pro-inflammatory
      molecules, which amplifies the Toll-like receptor-initiated responses to invading
      pathogens. In addition, TREM-1 mediates the septic shock pathway, and thus
      represents a potential therapeutic target. We report the crystal structure of the
      mouse TREM-1 extracellular domain at 1.76A resolution. The mouse extracellular
      domain is monomeric, consistent with our previous human TREM-1 structure, and
      strongly supports the contention that the globular TREM-1 head is a monomer
      contrary to proposals of a symmetric dimer.

PMID- 15561138
TI  - A family of anti-sigma70 proteins in T4-type phages and bacteria that are similar
      to AsiA, a Transcription inhibitor and co-activator of bacteriophage T4.
AB  - Anti-sigma70 factors interact with sigma70 proteins, the specificity subunits of
      prokaryotic RNA polymerase. The bacteriophage T4 anti-sigma70 protein, AsiA,
      binds tightly to regions 4.1 and 4.2 of the sigma70 subunit of Escherichia coli
      RNA polymerase and inhibits transcription from sigma70 promoters that require
      recognition of the canonical sigma70 -35 DNA sequence. In the presence of the T4
      transcription activator MotA, AsiA also functions as a co-activator of
      transcription from T4 middle promoters, which retain the canonical sigma70 -10
      consensus sequence but have a MotA box sequence centered at -30 rather than the
      sigma70 -35 sequence. The E.coli anti-sigma70 protein Rsd also interacts with
      region 4.2 of sigma70 and inhibits transcription from sigma70 promoters. Our
      sequence comparisons of T4 AsiA with Rsd, with the predicted AsiA orthologs of
      the T4-type phages RB69, 44RR, KVP40, and Aeh1, and with AlgQ, a regulator of
      alginate production in Pseudomonas aeruginosa indicate that these proteins share
      conserved amino acid residues at positions known to be important for the binding
      of T4 AsiA to sigma70 region 4. We show that, like T4 AsiA, Rsd binds to sigma70
      in a native protein gel and, as with T4 AsiA, a L18S substitution in Rsd disrupts
      this complex. Previous work has assigned sigma70 amino acid F563, within region
      4.1, as a critical determinant for AsiA binding. This residue is also involved in
      the binding of sigma70 to the beta-flap of core, suggesting that AsiA inhibits
      transcription by disrupting the interaction between sigma70 region 4.1 and the
      beta-flap. We find that as with T4 AsiA, the interaction of KVP40 AsiA, Rsd, or
      AlgQ with sigma70 region 4 is diminished by the substitution F563Y. We also
      demonstrate that like T4 AsiA and Rsd, KVP40 AsiA inhibits transcription from
      sigma70-dependent promoters. We speculate that the phage AsiA orthologs, Rsd, and
      AlgQ are members of a related family in T4-type phage and bacteria, which
      interact similarly with primary sigma factors. In addition, we show that even
      though a clear MotA ortholog has not been identified in the KVP40 genome and the
      phage genome appears to lack typical middle promoter sequences, KVP40 AsiA
      activates transcription from T4 middle promoters in the presence of T4 MotA. We
      speculate that KVP40 encodes a protein that is dissimilar in sequence, but
      functionally equivalent, to T4 MotA.

PMID- 15561139
TI  - Analysis of void volumes in proteins and application to stability of the p53
      tumour suppressor protein.
AB  - We have developed a new method for the analysis of voids in proteins (defined as
      empty cavities not accessible to solvent). This method combines analysis of
      individual discrete voids with analysis of packing quality. While these are
      different aspects of the same effect, they have traditionally been analysed using
      different approaches. The method has been applied to the calculation of total
      void volume and maximum void size in a non-redundant set of protein domains and
      has been used to examine correlations between thermal stability and void size.
      The tumour-suppressor protein p53 has then been compared with the non-redundant
      data set to determine whether its low thermal stability results from poor
      packing. We found that p53 has average packing, but the detrimental effects of
      some previously unexplained mutations to p53 observed in cancer can be explained
      by the creation of unusually large voids.

PMID- 15561140
TI  - Cycling of the Sm-like protein Hfq on the DsrA small regulatory RNA.
AB  - Small RNAs (sRNAs) regulate bacterial genes involved in environmental adaptation.
      This RNA regulation requires Hfq, a bacterial Sm-like protein that stabilizes
      sRNAs and enhances RNA-RNA interactions. To understand the mechanism of target
      recognition by sRNAs, we investigated the interactions between Hfq, the sRNA
      DsrA, and its regulatory target rpoS mRNA, which encodes the stress response
      sigma factor. Nuclease footprinting revealed that Hfq recognized multiple sites
      in rpoS mRNA without significantly perturbing secondary structure in the 5'
      leader that inhibits translation initiation. Base-pairing with DsrA, however,
      made the rpoS ribosome binding site fully accessible, as predicted by genetic
      data. Hfq bound DsrA four times more tightly than the DsrA.rpoS RNA complex in
      gel mobility-shift assays. Consequently, Hfq is displaced rapidly from its high
      affinity binding site on DsrA by conformational changes in DsrA, when DsrA base
      pairs with rpoS mRNA. Hfq accelerated DsrA.rpoS RNA association and stabilized
      the RNA complex up to twofold. Hybridization of DsrA and rpoS mRNA was optimal
      when Hfq occupied its primary binding site on free DsrA, but was inhibited when
      Hfq associated with the DsrA.rpoS RNA complex. We conclude that recognition of
      rpoS mRNA is stimulated by binding of Hfq to free DsrA sRNA, followed by release
      of Hfq from the sRNA.mRNA complex.

PMID- 15561141
TI  - Diversity of base-pair conformations and their occurrence in rRNA structure and
      RNA structural motifs.
AB  - In addition to the canonical base-pairs comprising the standard Watson-Crick (C:G
      and U:A) and wobble U:G conformations, an analysis of the base-pair types and
      conformations in the rRNAs in the high-resolution crystal structures of the
      Thermus thermophilus 30S and Haloarcula marismortui 50S ribosomal subunits has
      identified a wide variety of non-canonical base-pair types and conformations.
      However, the existing nomenclatures do not describe all of the observed non
      canonical conformations or describe them with some ambiguity. Thus, a
      standardized system is required to classify all of these non-canonical
      conformations appropriately. Here, we propose a new, simple and systematic
      nomenclature that unambiguously classifies base-pair conformations occurring in
      base-pairs, base-triples and base-quadruples that are associated with secondary
      and tertiary interactions. This system is based on the topological arrangement of
      the two bases and glycosidic bonds in a given base-pair. Base-pairs in the
      internal positions of regular secondary structure helices usually form with
      canonical base-pair groups (C:G, U:A, and U:G) and canonical conformations (C:G
      WC, U:A WC, and U:G Wb). In contrast, non-helical base-pairs outside of regular
      structure helices usually have non-canonical base-pair groups and conformations.
      In addition, many non-helical base-pairs are involved in RNA motifs that form a
      defined set of non-canonical conformations. Thus, each rare non-canonical
      conformation may be functionally and structurally important. Finally, the
      topology-based isostericity of base-pair conformations can rationalize base-pair
      exchanges in the evolution of RNA molecules.

PMID- 15561142
TI  - The heterodimeric primase of the hyperthermophilic archaeon Sulfolobus
      solfataricus possesses DNA and RNA primase, polymerase and 3'-terminal
      nucleotidyl transferase activities.
AB  - A eukaryotic-type primase was identified in the crenarchaeon Sulfolobus
      solfataricus. The two-subunit DNA-dependent primase, termed PriSL, was purified
      following co-expression of the subunits in Escherichia coli and its activity was
      characterised. PriSL was capable of utilising both ribonucleotides and
      deoxyribonucleotides for primer synthesis in the presence of natural, or
      synthetic, single-stranded DNA. A broad distribution of products was detected,
      ranging from dinucleotides to DNA molecules in excess of 7 kb and RNA up to 1 kb
      in length. However, PriSL had a significantly higher affinity for ribonucleotides
      than for deoxyribonucleotides. Using site-directed mutagenesis, two aspartate
      residues crucial for nucleic acid synthesis and residues important for the
      binding of free nucleotides were identified. In addition to the primase and
      polymerase activities, we reveal that the primase possesses a template
      independent 3'-terminal nucleotidyl transferase activity.

PMID- 15561143
TI  - ATP-dependent translocation of proteins along single-stranded DNA: models and
      methods of analysis of pre-steady state kinetics.
AB  - Processive DNA helicases are able to translocate along single-stranded DNA
      (ssDNA) with biased directionality in a nucleoside triphosphate-dependent
      reaction, although translocation is not generally sufficient for helicase
      activity. An understanding of the mechanism of protein translocation along ssDNA
      requires pre-steady state transient kinetic experiments. Although ensemble
      experimental approaches have been developed recently for the study of
      translocation of proteins along DNA, quantitative analysis of the complete time
      courses from these experiments, which is needed to obtain quantitative estimates
      of translocation kinetic parameters (rate constants, processivity, step sizes and
      ATP coupling) has been lacking. We discuss three ensemble transient kinetic
      experiments that can be used to study protein translocation along ssDNA, along
      with the advantages and limitations of each approach. We further describe methods
      to analyze the complete kinetic time-courses obtained from such experiments
      performed with a series of ssDNA lengths under "single-round" conditions (i.e. in
      the absence of re-binding of dissociated protein to DNA). These analysis methods
      utilize a sequential "n-step" model for protein translocation along ssDNA and
      enable quantitative determinations of the rate constant, processivity and step
      size for translocation through global non-linear least-squares fitting of the
      full time-courses.

PMID- 15561144
TI  - Mechanism of ATP-dependent translocation of E.coli UvrD monomers along single
      stranded DNA.
AB  - Escherichia coli UvrD protein is a 3' to 5' SF1 DNA helicase involved in methyl
      directed mismatch repair and nucleotide excision repair of DNA. Using stopped
      flow methods we have examined the kinetic mechanism of translocation of UvrD
      monomers along single-stranded DNA (ssDNA) in vitro by monitoring the transient
      kinetics of arrival of protein at the 5'-end of the ssDNA. Arrival at the 5'-end
      was monitored by the effect of protein on the fluorescence intensity of
      fluorophores (Cy3 or fluorescein) attached to the 5'-end of a series of
      oligodeoxythymidylates varying in length from 16 to 124 nt. We find that UvrD
      monomers are capable of ATP-dependent translocation along ssDNA with a biased 3'
      to 5' directionality. Global non-linear least-squares analysis of the full
      kinetic time-courses in the presence of a protein trap to prevent rebinding of
      free protein to the DNA using the methods described in the accompanying paper
      enabled us to obtain quantitative estimates of the kinetic parameters for
      translocation. We find that UvrD monomers translocate in discrete steps with an
      average kinetic step-size, m=3.68(+/-0.03) nt step(-1), a translocation rate
      constant, kt=51.3(+/-0.6) steps s(-1), (macroscopic translocation rate,
      mkt=189.0(+/-0.7) nt s(-1)), with a processivity corresponding to an average
      translocation distance of 2400(+/-600) nt before dissociation (10 mM Tris-HCl (pH
      8.3), 20 mM NaCl, 20% (v/v) glycerol, 25 degrees C). However, in spite of its
      ability to translocate rapidly and efficiently along ssDNA, a UvrD monomer is
      unable to unwind even an 18 bp duplex in vitro. DNA helicase activity in vitro
      requires a UvrD dimer that unwinds DNA with a similar kinetic step-size of 4-5 bp
      step(-1), but an approximately threefold slower unwinding rate of 68(+/-9) bp s(
      1) under the same solution conditions, indicating that DNA unwinding activity
      requires more than the ability to simply translocate directionally along ss-DNA.

PMID- 15561145
TI  - Changes in the structure of DNA molecules and the amount of DNA per plastid
      during chloroplast development in maize.
AB  - We examined the DNA from chloroplasts obtained from different tissues of juvenile
      maize seedlings (from eight to 16 days old) and adult plants (50-58 days old).
      During plastid development, we found a striking progression from complex
      multigenomic DNA molecules to simple subgenomic molecules. The decrease in
      molecular size and complexity of the DNA paralleled a progressive decrease in DNA
      content per plastid. Most surprising, we were unable to detect DNA of any size in
      most chloroplasts from mature leaves, long before the onset of leaf senescence.
      Thus, the DNA content per plastid is not constant but varies during development
      from hundreds of genome copies in the proplastid to undetectable levels in the
      mature chloroplast. This loss of DNA from isolated, mature chloroplasts was
      monitored by three independent methods: staining intact chloroplasts with 4',6
      diamidino-2-phenylindole (DAPI); staining at the single-molecule level with
      ethidium bromide after exhaustive deproteinization of lysed chloroplasts; and
      blot-hybridization after standard DNA isolation procedures. We propose a
      mechanism for the production of multigenomic chloroplast chromosomes that begins
      at paired DNA replication origins on linear molecules to generate a head-to-tail
      linear concatemer, followed by recombination-dependent replication.

PMID- 15561146
TI  - A domain interaction map based on phylogenetic profiling.
AB  - Phylogenetic profiling is a well established method for predicting functional
      relations and physical interactions between proteins. We present a new method for
      finding such relations based on phylogenetic profiling of conserved domains
      rather than proteins, avoiding computationally expensive all versus all sequence
      comparisons among genomes. The resulting domain interaction map (DIMA) can be
      explored directly or mapped to a genome of interest. We demonstrate that the
      performance of DIMA is comparable to that of classical phylogenetic profiling and
      its predictions often yield information that cannot be detected by profiling of
      entire protein chains. We provide a list of novel domain associations predicted
      by our method.

PMID- 15561147
TI  - Human deoxycytidine kinase as a deoxyribonucleoside phosphorylase.
AB  - Human deoxycytidine kinase (dCK) is a key enzyme in the 5'-phosphorylation of
      purine and pyrimidine deoxynucleosides with deoxycytidine as the most efficient
      substrate. The ability of dCK to degrade 2'-deoxyribonucleosides to free
      nucleobases and 2-deoxy-alpha-d-ribofuranose-1-phosphate was demonstrated by 1H
      31P correlation spectroscopy and by isotope enzyme kinetic methods. The reaction
      depended on inorganic phosphate, and dCK showed maximum cleavage activity between
      pH 7 and pH 8. In this pH range, [HPO4(2-)] is the dominant phosphate species,
      most likely being the phosphate donor. All natural deoxyribonucleosides could be
      cleaved and the Vmax of the phosphorylytic reaction compared to the kinase
      reaction was about 2-10%. The formation of free nucleobases occurred only with
      reduced dCK, because the reaction was highly dependent on the presence of
      reducing agents such as dithiotreitol. Thus, recombinant dCK can act as a
      phosphorylase, similar to the nucleoside phosphorylase family of enzymes. This
      catalytic activity is important for the design of in vitro experiments with dCK,
      such as crystallization and NMR spectroscopy.

PMID- 15561148
TI  - Structural bases of the redox-dependent conformational switch in the serpin PAI
      2.
AB  - Depending on the redox-status, the serpin plasminogen activator inhibitor type 2
      (PAI-2) can exist in either a stable monomeric or polymerogenic form. The latter
      form, which spontaneously forms loop-sheet polymers, has an open beta-sheet A and
      is stabilized by a disulfide bond between C79 (in the CD-loop) and C161 (at the
      bottom of PAI-2). Reduction of this bond results in a closing of the beta-sheet A
      and converts PAI-2 to a stable monomeric form. Here we show that the stable
      monomeric and polymerogenic forms of PAI-2 are fully interconvertible, depending
      on redox-status of the environment. Our intramolecular distance measurements
      indicate that the CD-loop folds mainly on one side of the stable monomeric form
      of the inhibitor. However, the loop can translocate about 54A to the bottom of
      PAI-2 so that the C79-C161 disulfide bond can form under oxidizing conditions. We
      show also that the redox-active C79 can form a disulfide-link to the matrix
      protein vitronectin, suggesting that vitronectin can stabilize active PAI-2 in
      extracellular compartments. PAI-2 is therefore a rare example of a redox
      sensitive protein for which the activity and polymerization ability are regulated
      by reversible disulfide bond formation leading to major translocation of a loop
      and significant conformational changes in the molecule.

PMID- 15561149
TI  - Solution structure of ribosomal protein L16 from Thermus thermophilus HB8.
AB  - Ribosomal protein L16 is an essential component of the bacterial ribosome. It
      organizes the architecture of aminoacyl tRNA binding site in the ribosome 50S
      subunit. The three-dimensional structure of L16 from Thermus thermophilus HB8 was
      determined by NMR. In solution, L16 forms an alpha+beta sandwich structure
      combined with two additional beta sheets located at the loop regions connecting
      the two layers. The terminal regions and a central loop region did not show any
      specific secondary structure. The structured part of L16 could be superimposed
      well on the C(alpha) model of L16 determined in the crystal structure of the
      ribosome 50S subunit. By overlaying the L16 solution structure onto the
      coordinates of the ribosome crystal structure, we constructed the combined model
      that represents the ribosome-bound state of L16 in the detailed structure. The
      model showed that L16 possesses residues in contact with helices 38, 39, 42, 43
      and 89 of 23S rRNA and helix 4 of 5S rRNA. This suggests its broad effect on the
      ribosome architecture. Comparison of L16 with the L10e protein, which is the
      archaeal counterpart, showed that they share a common fold, but differ in some
      regions of functional importance, especially in the N-terminal region. All known
      mutation sites in L16 that confer resistance to avilamycin and evernimicin were
      positioned so that their side-chains were exposed to solvent in the internal
      cavity of the ribosome. This suggests the direct participation of L16 as a part
      of the binding site for antibiotics.

PMID- 15561150
TI  - Interdomain contact regions and angles between adjacent short consensus repeat
      domains.
AB  - The short consensus repeat domain (SCR, complement control protein module, sushi
      domain) is a structural unit found in multiple adjacent copies in more than 40
      human proteins. Each bead-like domain is composed of approximately 60 residues
      and the adjacent domains are connected in a head-to-tail fashion with linkers
      that consist of two to 12 amino acid residues. Based on experimentally determined
      structures the neighbouring SCR domains interact with each other at the so-called
      hinge or interdomain contact region. The functions mediated by the SCR domains
      have been studied using mutagenesis but the possible effects of the mutations on
      the hinge regions and interdomain angles have not been analysed. In this study,
      the linker and three loops in conserved locations were found to be responsible
      for the interdomain contact regions of all the solved experimental structures.
      The interdomain contact regions were identified in sequences of 140 human SCR
      domain pairs, and distinct hydrophobic and charge features were found in
      different subsets of SCR proteins and functional domains. To compare the possible
      associations of the interdomain contact region characteristics to the interdomain
      orientations all the experimentally solved SCR structures were subjected to a
      uniform calculation of tilt, twist, and skew angles that define the interdomain
      orientation. The twist and skew angles were found to have a linear correlation
      and the spatial location of one loop of the N-terminal domain (N#1) was found to
      have an effect on the skew angle. Thus, we describe location of the interdomain
      contact regions in primary structures of SCR domains and report that the
      orientation of adjacent SCR domains is not random and depends partially on the
      interdomain contact regions. On the basis of these results, mutations within the
      interdomain contact regions and subsequent loss-of-function effects caused by
      changes in the interdomain orientation can be avoided in mutagenesis studies.

PMID- 15561151
TI  - The outer membrane usher forms a twin-pore secretion complex.
AB  - The PapC usher is an outer membrane protein required for assembly and secretion
      of P pili in uropathogenic Escherichia coli. P pilus biogenesis occurs by the
      chaperone/usher pathway, a terminal branch of the general secretory pathway.
      Periplasmic chaperone-subunit complexes target to the PapC usher for fiber
      assembly and secretion through the usher to the cell surface. The molecular
      details of pilus biogenesis at the usher, and protein secretion across the outer
      membrane in general, are unclear. We studied the structure and oligomeric state
      of PapC by gel filtration, dynamic light scattering, and electron microscopy and
      image analysis. Two-dimensional crystals of wild-type PapC and a C-terminal
      deletion mutant of PapC were produced by reconstituting detergent purified usher
      into E.coli lipids. PapC formed a dimer both in detergent solution and in the
      phospholipid bilayer. Cryo-electron microscopy revealed that the usher forms a
      twin-pore complex. Removal of the C-terminal domain did not change the basic
      shape of the PapC molecule, but altered the dimeric association of the usher,
      suggesting that the C terminus forms part of the dimerization interface. The
      overall molecular size (11 nm), pore size (2 nm), and twin-pore configuration of
      PapC resemble that of the Tom40 complex, a mitochondrial outer membrane protein
      translocase.

PMID- 15561152
TI  - A new lectin family with structure similarity to actinoporins revealed by the
      crystal structure of Xerocomus chrysenteron lectin XCL.
AB  - A newly defined family of fungal lectins displays no significant sequence
      similarity to any protein in the databases. These proteins, made of about 140
      amino acid residues, have sequence identities ranging from 38% to 65% and share
      binding specificity to N-acetyl galactosamine. One member of this family, the
      lectin XCL from Xerocomus chrysenteron, induces drastic changes in the actin
      cytoskeleton after sugar binding at the cell surface and internalization, and has
      potent insecticidal activity. The crystal structure of XCL to 1.4 A resolution
      reveals the architecture of this new lectin family. The fold of the protein is
      not related to any of the several lectin folds documented so far. Unexpectedly,
      the structure similarity is significant with actinoporins, a family of pore
      forming toxins. The specific structural features and sequence signatures in each
      protein family suggest a potential sugar binding site in XCL and a possible
      evolutionary relationship between these proteins. Finally, the tetrameric
      assembly of XCL reveals a complex network of protomer-protomer interfaces and
      generates a large, hydrated cavity of 1000 A3, which may become accessible to
      larger solutes after a small conformational change of the protein.

PMID- 15561154
TI  - Adolescents in transition of adult care: why the concern?
AB  - This article has described issues associated with transition planning for youth
      with CHD. A number of approaches have been described to address the needs of this
      growing number of youth with CHD. Transition to adulthood has been and will
      continue to be a significant clinical concern as the adult survival rate
      increases. Health care professionals who are involved in transition planning will
      be focused on the health-related concerns of the transfer to an ACHD,
      insurability, and long-term CHD management, as well as issues related to
      employment, education, social relationships, and independent living. Successful
      transitioning is dependent on long-term planning,. youth-centered approaches,
      service coordination, and referral to adult agencies. As youth, families, adult
      survivors, and experts have discovered, long-term survival means more than the
      physical aspects of CHD.

PMID- 15561155
TI  - Health care transition in congenital heart disease: the providers' view point.
AB  - Unfortunately, despite recommendations for educational training of ACHD health
      care providers and the goal to create regional ACHD centers, current needs still
      far outweigh appropriate available services. From a practical standpoint, we will
      need to work from our current models of health care delivery, which vary because
      of geographic and institutional issues and the availability of appropriate
      resources, toward the ideal goal of regional ACHD centers. Successful transition
      of adolescents and adults with CHD requires collaboration and planning between
      the pediatric health care team and the ACHD health care team. Good communication
      and an atmosphere of mutual respect are essential. All members of the ACHD health
      care team need to be committed to improving the process of transition for the
      adolescent and adult with CHD. The advanced practice nurse (CNS or ARNP) from
      both the pediatric program and the adult program are often key players in this
      process. As ACHD health care providers, we must work toward decreasing barriers
      to care and become organized advocates for our patients. Ultimately, our goal is
      not only to provide a smooth transition from one model of care to another, it is
      to create a health care delivery system that will maximize the lifelong potential
      and function of adults with congenital heart disease.

PMID- 15561156
TI  - Health care transitions for adolescents with congenital heart disease: patient
      and family perspectives.
AB  - Advances in medical management and surgical treatment have improved the longevity
      and quality of life for patients with CHD. However, meeting the health care needs
      of this growing population has not kept pace with the advances in technology.
      Adolescents with CHD are caught between both childhood and adulthood and
      pediatric and adult cardiology. As health care providers develop strategies to
      meet the special health care transition needs of this group, patient and family
      perspectives must be understood and included in the transition plan if one is to
      develop meaningful interventions. Assessment and recognition of the developmental
      changes occurring for both adolescents and their families and the impact of
      chronic illness on these changes are critical if transition is to be successful.
      Expectations,individual biases, and negative stereotypes need to be recognized
      and reframed if one is to establish an empathetic, positive, and trusting
      relationship with patients and their families. Greater sensitivity also needs to
      be given to the shifting roles, responsibilities, and inherent losses that occur
      with transition. Nurses have a key role in guiding patients and families toward
      adult, independent self-care by helping them identify and use their talents and
      resources as they move toward achieving their goals and dreams for the future.

PMID- 15561157
TI  - Transitional care issues influencing access to health care: employability and
      insurability.
AB  - Addressing the issues of employability and insurability remains a challenge for
      young adults with CHD, their parents, and health care professionals who care for
      this patient group. Because of their chronic condition, these young persons
      require ongoing access to health care, throughout their adult lives. Because most
      individuals obtain insurance through their place of employment (unless it is
      obtained under a spouse's policy), adolescents with CHD should begin to look
      carefully at career options that are compatible with their interests and their
      physical abilities. If it is more appropriate, assistance with referral to
      vocational rehabilitation programs may be given. Finally, guidance should include
      how to avoid issues of discrimination during a job interview and when working at
      one's place of employment. Legislation now supports many workers as long as they
      can carry out the job for which they were hired. With the continuing rise in cost
      of health care and health insurance coverage, young persons with CHD must
      understand the high importance of maintaining health care coverage for their
      chronic health condition, usually through a group plan in their place of
      employment. Current legislation supports supplemental coverage and portability of
      coverage when changing jobs, which minimizes or eliminates waiting periods for
      pre-existing conditions. Suggestions for ongoing health care are included not
      only for care by a cardiologist but noncardiac care, including a primary care
      practitioner, dental care, and obstetric-gynecologic care. With the size and life
      expectancy of this patient group growing each year, the issues of employability
      and insurability must continually be addressed by health care professionals in
      conjunction with government policy makers and insurance representatives. As
      additional long-term survival data become available on the natural history of
      CHD, it is hoped that insurance requirements will be modified to afford this
      group the insurance coverage needed to obtain adequate medical and financial
      security, with facilitated access to appropriate, high quality, and affordable
      health care.

PMID- 15561158
TI  - Educational and behavioral issues in transitioning from pediatric cardiology to
      adult-centered health care.
AB  - It is assumed that when they begin growing up, a child with congenital heart
      disease will take personal responsibility for his or her care. For this purpose,
      patients need sufficient knowledge on the heart defect, treatment,and measures to
      prevent complications. However, empirical studies indicated that the levels of
      knowledge and understanding of both parents and children with congenital heart
      disease are poor. Therefore, sound patient education is imperative, particularly
      when patients are transitioned from pediatric cardiology to adult congenital
      cardiology. In this respect, the focus of communication shifts from the parent to
      the young patient; moreover, education should be tailored according to the
      developmental level of the patient. Issues that should typically be covered by
      educational programs for adolescents with congenital heart disease are
      information on the heart defect, treatment, endocarditis, sexuality and
      reproduction, sports, employability and insurability, and cardiovascular risk
      factor. International guidelines indicate that advanced practice nurses are key
      in developing and implementing patient education programs during the transition
      from pediatric cardiology to adult-centered health care.

PMID- 15561159
TI  - Contraception for the adolescent and young adult with congenital heart disease.
AB  - Increasing numbers of females born with congenital heart disease are reaching
      childbearing age. Practitioners involved in the management of the adolescents or
      adults must be aware not only of the risks of pregnancy associated with varying
      types of CHD but with other issues involving the reproductive cycle to provide
      appropriate care, counseling, and education.

PMID- 15561160
TI  - Psychosocial issues affecting adults with congenital heart disease: one patient's
      perspective.
AB  - This article addresses a number of psychosocial issues that advance practice
      nurses and other health care providers should be aware of when working with
      patients who have congenital heart disease. If not properly addressed,
      particularly during adolescence, these issues can have a strong impact on a
      person's medical care and over-all quality of life. This article includes
      information from medical literature, conversations with adult patients, and my
      own experiences as both a patient with congenital heart disease and as a clinical
      social worker.

PMID- 15561162
TI  - Hypertension: a review for clinicians.
AB  - Despite the existence of a variety of consistent hypertension guidelines,the
      issue of inadequate management of the condition persists. The challenge for
      health care professionals is not only to understand and adopt the guidelines but
      also to take a holistic approach to patient care. In addition, clinicians need to
      encourage adherence to medication protocols, which will hopefully lead to an
      overall reduction in morbidity and mortality associated with hypertension. It is
      the clinician's professional responsibility to be cognizant of the emerging
      research on vasoactive substances as new drugs are being developed that will
      effect endothelial receptors. It is important that clinicians are trained
      appropriately in blood pressure measurement and risk factor identification and
      intervention.

PMID- 15561163
TI  - What's new in acute coronary syndrome?
AB  - Patients presenting with ACS are an exciting challenge for health care providers.
      It has been documented that hospitals that carry out evidence-based therapies
      related to ACS have reduced mortality rates and better outcomes in general. The
      use of evidence-based practices has been shown to be more difficult in women, the
      elderly, and nonwhite patients. This suggests that there are opportunities to
      make more substantial improvements in outcomes for these groups of individuals.
      There is a tremendous need to use the knowledge gained in treating patients with
      ACS. Surprisingly little is known about why health care professionals do not
      institute therapies that are based on quality evidence. What could the quality
      outcomes such as mortality rate be for ACS persons if there were widespread use
      of the knowledge already in the literature regarding the care of ACS clients?

PMID- 15561164
TI  - Nursing care of the client requiring percutaneous coronary intervention.
AB  - The scope of interventions for a wide variety of cardiac conditions and the
      research basis for practice are continuing to expand at a phenomenal rate. Nurses
      need to be actively engaged in all phases of the research process,to address
      ongoing questions of interest to continually improve client care. New research
      findings, building on an understanding of the foundations for interventional
      cardiology practice, are key to providing the highest quality of nursing care for
      this unique client population.

PMID- 15561165
TI  - Neurohormones and heart failure.
AB  - The management of several neurohormonal pathways is crucial to treating the
      progression of HF, in addition to improving the quality of life for patients
      diagnosed with HF. Stimulation of the sympathetic and retin-angiogensin
      aldosterone systems begins the initial and primary neurohormonal stimulation
      associated with the progression of this disease. However, it is becoming
      increasingly evident that other systems, including the cellular immune,
      endothelin-NO pathway, kallikrein-kinin system, the arachidonic acid cascade, and
      the natriuretic peptides need to be considered by clinicians when treating HF.
      Once treated solely with nitrates, diuretics, and morphine, the management of HF
      is becoming a more complex and intricate balancing act among several
      interdependent neurohormonal systems. Understanding the complex nature and proper
      management of these systems are crucial if patients with HF are to enjoy a better
      quality of life and experience an improvement in their symptoms. Current
      recommendations for the treatment and management of HF use several medications,
      which affect multiple neurohormonal pathways. The Heart Failure Society of
      America and the American Heart Association both recommend in their recent
      guidelines for management of HF the use of beta-adrenergic receptor blockers
      (beta-blockers), loop diuretics, digitalis glycosides(digoxin), ACE-I, aldactone
      antagonists (spironolactone), and in selected instances, ARBs and the combination
      of hydralazine and isosorbide dinitrate. No discussion of HF is complete without
      mention of the larger challenges associated with the management of HF. It is a
      complex syndrome that requires a multidisciplinary approach with expertise in
      nutrition, exercise, pharmacology, education, and the basic pathophysiology of
      complex neurohormonal systems. Patients with uncompensated HF are frightened,
      vulnerable, and require frequent medication adjustments as well as substantial
      time dedicated to counseling, physical assessment, and innovative educational
      programs for them and their families. In fact, a majority of hospital
      readmissions for HF occur because of patients' dietary indiscretions, medication
      noncompliance, or ignorance about when to call their health providers. The
      management of HF represents a careful balancing act between powerful
      neurohormonal pathways and medications but also between the basics of diet,
      exercise, educating both family and patient, and most importantly, caring.

PMID- 15561166
TI  - Management of cardiovascular disease in the elderly: a review of the Canadian
      Cardiovascular Society Consensus Conference.
AB  - Although Joan and Edward are fictitious characters, it is very likely we have
      encountered or will encounter patients with similar health concerns and daily
      life issues. As the population ages and our lifestyles continue to promote the
      development of cardiovascular disease, there is an increasing need to focus on
      the best ways to deal with this looming crisis. The CCS recognizes this pressing
      concern. The publication of the 2002 Consensus Conference assists all
      practitioners to work with their elderly patients to manage their heart disease
      most effectively. The CCS also recognizes the need for additional research.
      Throughout the document there is a continuous call for further study of best
      practice in the management and treatment of older adults with cardiovascular
      disease-stay tuned.

PMID- 15561167
TI  - Management and prevention of cardiovascular disease in women.
AB  - Cardiovascular disease, including coronary artery disease, hypertension, and
      stroke, is the number one killer of men and women in the United States and
      Canada. In the United States, cardiovascular disease accounts for more deaths in
      women, compared with men, every year since 1984. Unfortunately, many women are
      unaware of their risk for developing cardiovascular disease. This article reviews
      the statistics of this disease, identifies the risk factors, and reviews the
      evidence-based guidelines for prevention of cardiovascular disease in women.

PMID- 15561169
TI  - Frontiers in fetal cardiovascular disease.
AB  - This article reviews the state of the art in prenatal cardiovascular imaging, the
      elucidation of regional vascular flow patterns in the developing fetus and what
      can be learned from these flow patterns, the new clinical practice systems being
      that are being implemented to deal with the fetal patient and its family, and the
      prospects for fetal surgery.

PMID- 15561170
TI  - Fetal interventions for cardiac defects.
AB  - This article focuses on the current status of in utero catheter interventions for
      congenital heart disease. The discussion of fetal interventions for cardiac
      defects briefly reviews the evolution of approaches to congenital heart disease
      and issues surrounding the prenatal detection of cardiac defects, the rationale
      for fetal intervention, and optional candidates for the procedures. Finally, the
      technical aspects and procedural considerations are reviewed.

PMID- 15561171
TI  - The physiology of cardiac auscultation.
AB  - Cardiac auscultation remains a critical component of the pediatric examination
      and is the primary method of diagnosis for the common innocent murmurs of
      childhood. This article outlines the significance of auscultation and defines the
      skills important for the diagnosis and recognition of common cardiac murmurs in
      childhood. The origin of heart sounds and murmurs is reviewed, and an approach to
      pediatric murmur evaluation is presented. The seven innocent murmurs of childhood
      and adolescence are reviewed in detail. Further diagnostic evaluation and
      referral depends the clinician's confidence and experience in recognizing and
      correctly characterizing these murmurs.

PMID- 15561172
TI  - Evaluation of the child with an arrhythmia.
AB  - Several recent technologic innovations will expand the therapeutic alternatives
      available to children with arrhythmia. Despite these advances, the management of
      these patients still requires a solid foundation of clinical skill and judgment.
      The primary care pediatric practitioner is often the first one to recognize the
      symptoms and signs of an arrhythmia. Careful assessment of the history, physical
      examination, and electrocardiogram is necessary for making the correct diagnosis.

PMID- 15561173
TI  - Chest pain in children and adolescents.
AB  - The focus of this article is to explore chest pain in children and adolescents.
      Common causes of chest pain and the approach to its evaluation are reviewed.
      Special emphasis is given to the cardiac causes of pediatric chest pain and how
      it can be differentiated from more common benign etiologies.

PMID- 15561174
TI  - Exercise testing in pediatrics.
AB  - This article discusses exercise physiology and its application in the pediatric
      population. This article discusses exercise physiology and its application in the
      pediatric population. The authors briefly review the normal physiologic response
      to exercise. They then discuss populations in which exercise testing is most
      useful, the indications and contraindications for graded exercise, and the usual
      parameters that are measured during testing. Finally, the authors review some of
      the recent data on exercise performance in specific pediatric populations.

PMID- 15561175
TI  - Pediatric interventional catheterization: reasonable expectations and outcomes.
AB  - This article considers the role transcatheter therapy plays in the treatment of
      each major type of congenital heart lesion. The focus is on the clinical
      ramifications of the interventions rather than their technical aspects.

PMID- 15561176
TI  - Newborn heart surgery: reasonable expectations and outcomes.
AB  - This article discusses the necessity for standards for reasonable expectations
      and outcomes for neonatal treatment of congenital heart disease and the databases
      that allow such standards to be measured and to be compared among treatment
      centers.

PMID- 15561177
TI  - Academic performance and behavioral difficulties after neonatal and infant heart
      surgery.
AB  - Although advances in medical and surgical arenas have allowed the ability to
      "mend" children born with congenital heart disease, the increasing number of
      survivors has created a growing cohort of children with potential academic
      difficulties. This article reviews the current understanding of the midterm
      neurologic outcomes of children who underwent neonatal and infant cardiac
      surgery. Lesions including transposition of great arteries, tetralogy of Fallot,
      hypoplastic left heart syndrome, total anomalous pulmonary venous connection, and
      single ventricle lesions requiring Fontan palliation or cardiac transplantation
      are discussed.

PMID- 15561178
TI  - Training pediatric residents to evaluate congenital heart disease in the current
      era.
AB  - Working with young pediatricians to create an exciting educational environment in
      which to learn cardiology remains a challenge for all of us. Numerous forces
      impact our efforts, making the process of training residents to evaluate and
      treat congenital heart disease in the current era a dynamic and, at times,
      difficult endeavor. This article considers the changes that have occurred in the
      medical school graduate who chooses pediatrics and subsequently pediatric
      cardiology as a career; explores the changes in the graduate medical training
      guidelines, requirements, and restrictions that have been put into place within
      the last several years; and discusses the seemingly constant advances in
      scientific understanding and technology that shape our field and move us forward
      as a discipline.

PMID- 15561179
TI  - Sudden death in children and adolescents.
AB  - This article focuses on sudden unexpected cardiac death (SCD) in children and
      adolescents. The authors discuss the epidemiology of SCD in children and
      adolescents, its incidence and etiologies, and strategies for prevention. Because
      most of the episodes of SCD or sudden cardiac arrest in children and adolescents
      occur in asymptomatic individuals unknown to have an underlying abnormality
      before their "event," the issues in this article primarily focus on this group of
      individuals.

PMID- 15561180
TI  - The current epidemic of childhood obesity and its implications for future
      coronary heart disease.
AB  - This article acquaints readers with the data sources documenting the dramatic
      increases of overweight and obesity in the United States in the past 40 years,
      explains the reference standards for ascertaining measures of overweight in
      adults and children, and cites evidence that establishes obesity as a risk factor
      for premature death. Also reviewed are reports documenting recent increases in
      the frequency of type 2 diabetes mellitus and glucose intolerance and selected
      reports emanating from four longitudinal studies performed in large populations
      of adults, children, and adolescents linking excessive adiposity to coronary
      heart disease risk factors. A brief discussion of the challenges that
      pediatricians and other primary care health providers face in helping to diminish
      the prevalence of obesity and its attendant health problems is presented.

PMID- 15561181
TI  - Fetal and childhood onset of adult cardiovascular diseases.
AB  - Childhood onset of adult cardiovascular disease has become a significant public
      health problem. Whether genetic, environmental, or fetal influences are the
      primary culprits in the epidemic of the cardiovascular disease seen today remains
      unknown. The benefits of an overall physically active lifestyle that includes
      weight control, lower blood pressure, avoidance of tobacco use, and consistent
      exercise are clear and can impact the overall health of children and adolescents.
      Physicians who care for children and adolescents must begin to incorporate
      screening of adult cardiovascular disorders into their practice. Better
      understanding of the etiology of these disease states will bring with it enhanced
      preventive and targeted therapies.

PMID- 15561182
TI  - The genetic contribution to congenital heart disease.
AB  - This article reviews the more recent findings on the genetic basis of congenital
      cardiovascular disease and highlights the clinical applications of these
      discoveries.

PMID- 15561183
TI  - Transitioning the young adult with congenital heart disease for life-long medical
      care.
AB  - Guidelines for the successful orchestration of transitioning of the adolescent
      and young and older adult patient with congenital heart disease to a health care
      system appropriate for their long-term congenital heart disease care and
      counseling appear necessary to improve patient and family confidence, education,
      therapy, life quality, and survival outcomes. Schema for care organization and
      delivery for adult patients with congenital heart disease remain primitive and
      largely unimplemented. The presence of a strong central care oversight
      organization and the establishment of a multi-institutional database to assist in
      assessment of care outcomes and guidelines appears requisite to these needs and
      for the establishment of transitioning guidelines for these patients as they
      assume a greater and deeper shared control of their futures with their
      caregivers.

PMID- 15561184
TI  - A cyanobacterial protein with similarity to phytochelatin synthases catalyzes the
      conversion of glutathione to gamma-glutamylcysteine and lacks phytochelatin
      synthase activity.
AB  - Phytochelatins are glutathione-derived, non-translationally synthesized peptides
      essential for cadmium and arsenic detoxification in plant, fungal and nematode
      model systems. Recent sequencing programs have revealed the existence of
      phytochelatin synthase-related genes in a wide range of organisms that have not
      been reported yet to produce phytochelatins. Among those are several
      cyanobacteria. We have studied one of the encoded proteins (alr0975 from Nostoc
      sp. strain PCC 7120) and demonstrate here that it does not possess phytochelatin
      synthase activity. Instead, this protein catalyzes the conversion of glutathione
      to gamma-glutamylcysteine. The thiol spectrum of yeast cells expressing alr0975
      shows the disappearance of glutathione and the formation of a compound that by LC
      MSMS analysis was unequivocally identified as gamma-glutamylcysteine. Purified
      recombinant protein catalyzes the respective reaction. Unlike phytochelatin
      synthesis, the conversion of glutathione to gamma-glutamylcysteine is not
      dependent on activation by metal cations. No evidence was found for the
      accumulation of phytochelatins in cyanobacteria even after prolonged exposure to
      toxic Cd2+ concentrations. Expression of alr0975 was detected in Nostoc sp. cells
      with an antiserum raised against the protein. No indication for a responsiveness
      of expression to toxic metal exposure was found. Taken together, these data
      provide further evidence for possible additional functions of phytochelatin
      synthase-related proteins in glutathione metabolism and provide a lead as to the
      evolutionary history of phytochelatin synthesis.

PMID- 15561185
TI  - NMR-based metabonomic study of transgenic maize.
AB  - The aim of this research was to verify the possibility of identifying and
      classifying maize seeds obtained from transgenic plants, in different classes
      according to the modification, on the basis of the concerted variation in
      metabolite levels detected by NMR spectra. It was possible to recognise the
      discriminant metabolites of transgenic samples as well as to classify non-a
      priori defined samples of maize. It is important to underline that the obtained
      results are useful to point out the metabolic consequences of a specific genic
      modification on a plant, without using a targeted analysis of the different
      metabolites, in fact it was possible to classify the seeds also without the
      complete assignment of the spectra. The analysis was performed by applying
      multivariate techniques (principal component analysis and partial least squares
      discriminant analysis) to NMR data.

PMID- 15561186
TI  - Oxidation of 8'-hydroxy abscisic acid in Black Mexican Sweet maize cell
      suspension cultures.
AB  - In a biotransformation study to prepare deuterium labelled phaseic acid (PA) from
      deuterated abscisic acid (ABA), the product contained fewer deuterium atoms than
      expected. Thus, spectroscopic data of isolated deuterated PA prepared from
      biotransformation of (+)-5,8',8',8'-d4-ABA in maize (Zea mays L. cv. Black
      Mexican Sweet) cell suspension cultures showed 83% deuterium incorporation at the
      8'-exo position. Also, metabolism studies of (+)-4,5-d2-ABA in maize resulted in
      the isolation of deuterium labelled ABA derivatives, namely PA, dihydrophaseic
      acid (DPA), 4'-O-beta-D-glucopyranosylDPA, 8'-hydroxyPA, 8'-hydroxyDPA and 8'
      oxoDPA, as deduced from spectroscopic methods. These combined results suggested
      the presence of an aldehyde intermediate which is either: (a) reduced to 8'
      hydroxyABA and cyclized to PA, or (b) is hydrated and cyclized to 8'-hydroxyPA or
      (c) is further oxidized to the acid and cyclized to 8'-oxoPA. The chemical
      synthesis of this intermediate, as well as its biotransformation in maize cell
      cultures is presented.

PMID- 15561187
TI  - Analysis of volatiles from black pine (Pinus nigra): significance of wounding and
      egg deposition by a herbivorous sawfly.
AB  - The composition of headspace volatiles of black pine (Pinus nigra) was analysed
      by coupled gas chromatography-mass spectrometry (GC-MS). It has been shown in a
      previous study that egg deposition of the sawfly Diprion pini on P. sylvestris
      induces a quantitative change of the pine volatile blend . Chrysonotomyia
      ruforum, an egg parasitoid of D. pini, is known to be attracted by volatiles from
      egg-carrying P. sylvestris, but not by odour from egg-laden P. nigra. Therefore,
      the present study focused on the question whether also P. nigra as another host
      plant of this sawfly responds to egg deposition by change of its volatile blend.
      The headspace of untreated, egg-carrying, and artificially wounded P. nigra twigs
      were compared. The artificial damage inflicted to the twigs mimicked the damage
      by the sawfly female prior to egg deposition. Thirty five mainly terpenoid
      compounds that were identified in more than 50% of the egg-carrying P. nigra
      twigs could also be detected in the headspace of untreated and artificially
      wounded twigs. Quantitative differences of the blends of volatiles from
      differently treated P. nigra twigs were compared by multivariate data analyses.
      PLS-DA (projection to latent structures-discriminant analysis) revealed that
      blends of volatiles from differently treated P. nigra differed significantly.
      When comparing volatiles from egg-carrying and artificially wounded P. nigra with
      respective P. sylvestris samples, qualitative and quantitative differences were
      detected. The differences in volatile composition of P. nigra and P. sylvestris
      are discussed with special respect to the egg parasitoid's response to odours of
      egg-carrying pine twigs.

PMID- 15561188
TI  - Comparison of an inducible oxidative burst in free-living and symbiotic
      dinoflagellates reveals properties of the pseudopterosins.
AB  - An oxidative burst in free-living and symbiotic dinoflagellates induced by
      physical stress is defined and characterized. The oxidative burst occurred within
      1 min of physical injury caused by short pulses of low frequency sonic sound (20
      kHz, 10 s pulses). The quantities of reactive oxygen species were measured using
      a spectrofluorometric assay and standardized to hydrogen peroxide. Using
      pharmacological probes, the oxidative burst was found to contain upwards of 95%
      hydrogen peroxide and was believed to be of enzymatic origin. Symbiotic
      dinoflagellates of the genus Symbiodinium sp. isolated from the gorgonian coral
      Pseudopterogorgia elisabethae produced a burst that was less than 33% of the
      magnitude of the oxidative burst in Symbiodinium sp. isolated from
      Pseudopterogorgia americana and less than 2% of the magnitude of the oxidative
      burst in the related free-living dinoflagellate, Heterocapsa pygmaea. We recently
      reported that Symbiodinium sp. from Pseudopterogorgia elisabethae contain high
      levels of the unique diterpene metabolites, the pseudopterosins, not found in the
      free-living Heterocapsa pygmaea and Symbiodinium sp. isolated from
      Pseudopterogorgia americana. Pseudopterosins completely blocked the inducible
      oxidative burst when applied exogenously to these two dinoflagellate species.
      Preliminary evidence is presented that raises the possibility that the mechanism
      could involve inhibition of G-protein activation among many possibilities. These
      data are the first description of an inducible oxidative burst in
      dinoflagellates. The significance of the comparative oxidative burst in free
      living and symbiotic dinoflagellates is discussed and the potential natural role
      of the pseudopterosins is postulated.

PMID- 15561189
TI  - Azoxyglycoside content and beta-glycosidase activities in leaves of various
      cycads.
AB  - Azoxyglycoside contents in leaves of 32 cycad species belonging to 10 cycad
      genera and the seeds of 4 Encephalartos species were analyzed by HPLC with a YMC
      PA03 amide column. Azoxyglycosides were detected in mature leaves of 14 cycad
      species including 2 Bowenia, 2 Lepidozamia, 1 Microcycas, and 1 Stangeria
      species, but not in mature leaves of 18 other cycad species; 2 of 3 Ceratozamia,
      1 of 3 Cycas, 3 of 3 Dioon, 10 of 11 Encephalartos, 1 of 3 Macrozamia and 1 of 3
      Zamia species analyzed. The ratios of beta-glycosidase activity toward cycasin
      and macrozamin in extracts from the leaves of 9 species belonging to 9 genera
      were measured. The hydrolysis of cycasin was higher in the leaf extracts of Cycas
      revoluta, Bowenia spectabilis, Stangeria eriopus and Ceratozamia mexicana,
      whereas in Lepidozamia hopei, the hydrolysis levels of cycasin and macrozamin
      were similar. On the other hand, activity toward macrozamin was higher in Dioon
      edule, Encephalartos villosus, Macrozamia miquelii and Zamia fischeri. The
      hydrolytic activities in most species were estimated to be sufficient for the
      release of methylazoxymethanol in leaves analogous to the cyanogenesis of
      cyanogenic plants. Therefore, hydrolysis of azoxyglycosides by endogenous
      glycosidase in leaves seems to occur by accidental injury of leaves. However, in
      M. miquelii leaf extract, hydrolytic activity toward macrozamin was high and the
      activity toward cycasin was very low, though only cycasin was found in the leaves
      of this species.

PMID- 15561190
TI  - Antibacterial and resistance modifying activity of Rosmarinus officinalis.
AB  - As part of a project to characterise plant-derived natural products that modulate
      bacterial multidrug resistance (MDR), bioassay-guided fractionation of a
      chloroform extract of the aerial parts of Rosmarinus officinalis led to the
      characterisation of the known abietane diterpenes carnosic acid (1), carnosol (2)
      and 12-methoxy-trans-carnosic acid. Additionally, a new diterpene, the cis A/B
      ring junction isomer of 12-methoxy-trans-carnosic acid, 12-methoxy-cis-carnosic
      acid (5), was isolated. The major components were assessed for their
      antibacterial activities against strains of Staphylococcus aureus possessing
      efflux mechanisms of resistance. Minimum inhibitory concentrations ranged from 16
      to 64 microg/ml. Incorporation of 1 and 2 into the growth medium at 10 microg/ml
      caused a 32- and 16-fold potentiation of the activity of erythromycin against an
      erythromycin effluxing strain, respectively. Compound 1 was evaluated against a
      strain of S. aureus possessing the NorA multidrug efflux pump and was shown to
      inhibit ethidium bromide efflux with an IC50 of 50 microM, but this activity is
      likely to be related to the inhibition of a pump(s) other than NorA. The
      antibacterial and efflux inhibitory activities of these natural products make
      them interesting potential targets for synthesis.

PMID- 15561191
TI  - Globoidnan A: a lignan from Eucalyptus globoidea inhibits HIV integrase.
AB  - An HTS campaign aimed at the identification of inhibitors of HIV integrase showed
      that the methanol extract from the buds of a Eucalyptus globoidea was active.
      Bioassay guided fractionation of this extract resulted in the purification and
      structural elucidation of the lignan, globoidnan A (1) as the only compound in
      the extract responsible for the inhibition of HIV integrase. The compound was
      found to inhibit the combined 3' processing and strand transfer activity of HIV
      integrase with an IC50=0.64 microM.

PMID- 15561192
TI  - The content of indigo precursors in Isatis tinctoria leaves--a comparative study
      of selected accessions and post-harvest treatments.
AB  - We recently clarified the nature of indigo precursors in woad (Isatis tinctoria
      L.), by identifying the major indoxyl glycoside as isatan A (indoxyl-3-O-(6'-O
      malonyl-beta-D-ribohexo-3-ulopyranoside)), and by correcting the structure of the
      related isatan B (indoxyl-3-O-beta-D-ribohexo-3-ulopyranoside). A quantitative
      densitometric assay for isatans A and B, and indican, was established and
      validated. HPTLC separation on silica gel was followed by densitometric analysis
      of indigoid pigments formed after treatment with dilute acid or base. The
      seasonal variation of indoxyl glycosides in woad leaves was investigated with
      first-year plants (rosette stage) of five defined I. tinctoria L. and one I.
      indigotica L. accessions. Isatan A content reached up to 7.6% of dry weight in I.
      tinctoria, and up to 21.8% in I. indigotica. The influence of various post
      harvest treatments was studied. High concentrations of isatans A and B were found
      in freeze-dried leaf samples, whereas the content of indican was lowest.
      Conventional drying at ambient or 40 degrees C led to complete disappearance of
      isatans A and B. The concentration of indican, in contrast, was 3- to 5-fold
      higher in leaf samples submitted to drying at ambient and 40 degrees C,
      respectively.

PMID- 15561193
TI  - Regiospecific oxygenation of alkenones in the benthic haptophyte Chrysotila
      lamellosa Anand HAP 17.
AB  - Two groups of previously unidentified C37-C39 epoxyalkenones and alkenediones
      were detected in late stationary phase cultures of the haptophyte microalga
      Chrysotila lamellosa. The formation of these compounds is attributed to the
      involvement of enzymatic processes acting specifically on the C-21 or C-22
      allylic carbon and the omega15 double bond of methyl and ethyl alkenones
      respectively. Thus, the epoxyalkenones appear to be derivatives of alkenones
      where the omega15 double bond is oxidized to the epoxide. These epoxyalkenones
      disappear as the cells age to be replaced by a series of alkenediones. The
      structures of these compounds indicate that they are derivatives of methyl and
      ethyl alkenones with an additional carbonyl group on the C-21 or C-22 carbon
      respectively and without the omega15 double bond. We propose that these compounds
      are formed by an initial regiospecific lipoxygenase-catalyzed peroxidation of
      methyl and ethyl alkenones on their C-21 or C-22 allylic carbon, respectively.
      Lipohydroperoxidase-catalyzed homolytic cleavage of the O-O bond could then
      result in the formation of conjugated ketones which may then undergo a saturation
      reaction to form the diketones identified. This work demonstrates that alkenones
      can be degraded by enzymatic reactions in senescent cells, and by implication
      this could also occur in the natural environment.

PMID- 15561194
TI  - Monoterpenoids and their glycosides from the leaf of thyme.
AB  - From the polar portion of the methanol extract of thyme (leaf of Thymus vulgaris;
      Labiatae), which has been used as an important stomachic, carminative, a
      component of prepared cough tea, and a spice, seven monoterpenoid glycosides were
      isolated together with two known monoterpenoids and three known monoterpenoid
      glucosides. Structures of the seven monoterpenoid glycosides were determined by
      spectral analysis.

PMID- 15561195
TI  - Analysis of clinical variables of donors and recipients with respect to short
      term graft outcome in human liver transplantation.
AB  - Donor and recipient factors are closely associated with graft survival after
      orthotopic liver transplantation (OLT). This study was performed to analyze
      clinical characteristics of recipients and donors, which affect 30-day graft loss
      after OLT. MATERIALS AND METHODS: One hundred eighty-six livers from heart
      beating donors were accepted between May 1997 and June 1998 at the University of
      Pittsburgh Medical Center. Donor variables that were analyzed included age, sex,
      cold ischemia time (CIT), warm ischemia time (WIT), imported versus local
      procurement, cardiopulmonary arrest, serum sodium level, and dopamine dose. The
      recipient characteristics included native liver disease and UNOS status. Two
      sided Fisher exact test and stepwise logistic regression were used for univariate
      and multivariate analyses. P-values < .05 were considered statistically
      significant. RESULTS: Twenty-eight grafts (15.1%) were lost within 30 days of
      OLT. The following factors were found to adversely affect graft survival: donor
      sodium > 155 mEq/L (P = .002); CIT > 12 hours (P = .002); WIT > 45 minutes (P =
      .002); and imported liver graft (P = .048). Logistic regression revealed that
      donor sodium (odds ratio, 3.03; 95% CI, 1.05 to 8.74), CIT (OR 1.20; 95% CI 1.05
      to 1.38), WIT (OR 1.06; 95% CI 1.01 to 1.09) were independent predictors of early
      graft loss. CONCLUSION: Donor hypernatremia as well as warm and cold ischemia
      times independently affect graft outcomes in the early postoperative period after
      OLT. Avoidance of long preservation and correction of donor sodium level are
      recommended to optimize results and survival in OLT.

PMID- 15561196
TI  - Usefulness of the prognostic score for donor safety in living donor liver
      transplantation.
AB  - This study sought to determine whether a prognostic score is a useful indicator
      of donor safety using 13 consecutive donors enrolled for liver transplantation.
      The donor operations were right hepatic lobectomies (n = 10) and left hepatic
      lobectomies (n = 3). The postoperative maximal level of serum total bilirubin was
      used to assess the magnitude of surgical stress. Variables such as donor age,
      percentage of liver resection (PLR), indocyanine green 15-minute retention rate
      (ICGR15), operative blood loss, operation time, prognostic score and graft weight
      were evaluated as predictors of the magnitude of surgical stress. The PLR and
      prognostic score (PS) were calculated according to the following formulae: PLR
      (%) = 100*Graft weight (g)/standard liver volume of the donor (mL); PS = -84.6 +
      0.933*PLR (%) +1.11*ICGR15 (%) +0.999*age (years); Standard liver volume (mL) =
      706.2*body surface area (m2) + 2.39. No serious complications occurred after the
      donor operations. Maximal bilirubin ranged from 1.9 to 10.9 mg/dL. There were no
      mortalities, although there were two morbidities, bile leakage and prolonged
      liver dysfunction. Postoperative hyperbilirubinemia was observed in two donors
      and in one Gilbert's syndrome donor. Linear regression analysis of each variable
      indicated poor correlations between those variables and maximal bilirubin.
      However, close correlations were seen between maximal bilirubin and both donor
      age and PS except for the three patients who showed postoperative
      hyperbilirubinemia. In these uneventful donors, statistical formulae were
      obtained as follows: maximal bilirubin (PMB) = 0.271 + 0.056*donor age
      (correlation coefficient 0.612, P < .008), PMB = 1.541 + 0.059*PS (correlation
      coefficient 0.597, P < .009). In conclusion, PS is useful to predict maximal
      bilirubin and to ensure donor safety.

PMID- 15561197
TI  - The challenge of finding donors for living donor liver transplantation in Saudi
      Arabia.
AB  - INTRODUCTION: Organ shortage remains the main limiting factor for expanding liver
      transplantation (LT) in Saudi Arabia. Therefore, living donor liver
      transplantation (LDLT) was recently undertaken by our team at King Faisal
      Specialist Hospital and Research Center (KFSH&RC), in an effort to meet the
      increasing demand for LT in Saudi Arabia. OBJECTIVE: Analysis of donors assessed
      for LDLT at KFSH&RC. METHODS: Between September 2002 and May 2003, 39 potential
      donors were assessed for LDLT. First- or second-degree relationship to the
      recipient was an essential precondition. Assessment included biochemical testing,
      radiological studies (computed tomography: magnetic resonance angiography,
      magnetic resonance cholangiography), and thorough psychosocial analysis. Liver
      biopsy and hepatic angiogram was performed in some but not all donors. RESULTS:
      Male:female ratio was 28:11. Median age was 27 (18 to 34). Of 39 potential
      donors, only three underwent LDLT. The remaining 36 were rejected for different
      reasons including: psychosocial in 8 (20.5%), fatty liver in 7 (17.9%), recipient
      issues in 6 (15.4%), refusal after initial approval in 3 (7.7%), unfavorable
      anatomy in 2 (5.1%), inadequate liver volume in 2 (5.1%), abnormal liver
      functions in 2 (5.1%), hepatitis C virus in 2 (5.1%), liver pathology in 1
      (2.6%), and other medical concerns in remaining 3 donors (7.7%). CONCLUSION: In
      Saudi Arabia, donor availability as well as recipient characteristics may limit
      the value of LDLT in overcoming organ shortage. Therefore, efforts should be
      directed to improve the number and quality of available cadaveric organs. Until
      then, LDLT may be the only way forward to save patients from dying on the waiting
      list.

PMID- 15561198
TI  - Complications of liver donation for living related liver transplantation.
AB  - Living related liver transplantation (LRLT) has gained popularity, especially in
      Asian countries as the primary mode of liver transplantation. LRLT, however,
      carries the inherent problem of potential donor harm. In view of reports of donor
      deaths and significant donor morbidity (as high as 67%), we examined donor
      complication rates in our LRLT program. All sixteen LRLT donors between February
      2000 and January 2003 were retrospectively analyzed. The 16 donors (13 men, 3
      women) of mean age 30 years (range, 18-49 years) included 5 donations from
      siblings, 2 from parents, and 9 from offsprings. The portion of liver donated was
      L hepatectomy (n = 4) R hepatectomy (n = 7), and Modified Extended R hepatectomy
      (n = 5) with the weight of resected liver being 618.9 g (range, 380-1000). The
      mean blood loss was 936 mL (range, 400-1900 mL), but only 2 donors required
      transfusion of banked blood. The mean intensive care unitstay was 1.06 days
      (range, 1-2 days) and the mean hospital stay was 9.12 days (range, 7-14 days).
      There was no case of reoperation and no mortality. There was no biliary or
      vascular complication. Four of 16 (25%) donors had a minor morbidity; 2 of 16
      (12.5%) had a morbidity requiring intervention. In conclusion, with meticulous
      preoperative, intraoperative, and postoperative management, successful LRLT can
      be performed with minimal donor morbidities.

PMID- 15561199
TI  - Liver transplantation for acute hepatic failure.
AB  - INTRODUCTION: The mortality rate of acute hepatic failure (AHF) with conservative
      treatment is 40% to 90%, depending on the etiology. Hepatitis B infection is the
      major cause of AHF in Asia. In this study, we examined the role of liver
      transplantation for adult patients with AHF. METHODS: Sixteen patients with AHF
      received liver transplants in the past 6 years. Eight patients received cadaveric
      donor and another 8 living-related donor grafts. Fifteen patients suffered from
      hepatitis B-related disease and 1 had drug-induced AHF. Extracorporeal charcoal
      hemoperfusion was used as a bridge to liver transplantation in the first 2
      patients and plasma exchange was used in the following patients. RESULTS: One
      patient died 1 month after the operation due to primary nonfunction. The other 15
      patients are alive with good graft function at 2 months to 6 years follow-up. The
      success rate is 94%. Postoperative complications included infection in 10
      patients (62.5%), acute rejection in 4 patients (25%), and biliary complication
      in 2 patients (12.5%). No neurological complications were noted. CONCLUSION:
      Liver transplantation is the most effective treatment for patients with AHF.
      Living donors may be considered due to the organ shortage and the critical
      patient disease.

PMID- 15561200
TI  - Auxiliary partial orthotopic liver transplantation in the treatment of acute
      liver failure: a case report.
AB  - A successful experience with auxiliary partial orthotopic liver transplantation
      (APOLT) for acute liver failure is reported in a 29-year-old woman who
      experienced jaundice, generalized erythema for 7 days, and decreased mentation
      for 3 days. Two months prior, she suffered pulmonary tuberculosis, being
      currently treated with antituberculous medications, which caused the fulminant
      hepatic failure. We decided to perform APOLT based on two facts. The first was
      the possibility that the diseased native liver may recover sufficiently to
      withdraw the immunosuppressants. Second, the pulmonary tuberculosis may have been
      worsened by immunosuppression. We removed the extended lateral section of the
      recipient for the graft. The left hepatic vein of the extended left lateral graft
      was anastomosed to the left hepatic vein of the recipient. The left portal vein
      of the graft was anastomosed to the left portal vein of the recipient. The right
      portal vein of the recipient was left without any manipulation. A duct-to-duct
      anastomosis was performed. On postoperative day 3, antituberculous medications
      were started. On the postoperative day 37, she was discharged without any
      problems. On the postoperative day 120, she showed no event of rejection, and her
      pulmonary symptoms improved. We performed the operation without transection of
      the portal branch to the native liver, but no functional competition has been
      discovered.

PMID- 15561201
TI  - Successful listing of patients for liver transplant was related to participation
      of referring doctor in the transplant program.
AB  - INTRODUCTION: Experience with liver transplantation is limited in many parts of
      Asia. Therefore, patients from nontransplant centers may not be referred in a
      timely fashion for transplants. Our aim was to evaluate the pattern of referral
      for liver transplantation and their outcomes in Singapore. METHODS: Consecutive
      patients referred from 1990 to 2001 were reviewed. Patients from any hospital in
      Singapore (or the region) could be referred to the program. They were discussed
      at the weekly meetings. Appropriate patients were placed on the waiting list.
      "Pending" indicated that the disease was early or there were unsettled medical or
      social issues. Unsuitable patients were "rejected" for transplant. RESULTS: There
      were 385 patients referred over a 12-year period. Hepatitis B cirrhosis and
      hepatocellular carcinoma (HCC) were the most common indications among adults,
      whereas biliary atresia was the most common for children. Pediatric patients were
      more likely than adult patients to be listed for transplant (53/76 vs 106/309, P
      < .001). Patients referred by regular attendees of the program were more likely
      to be accepted than nonattendees (38% vs 25%, P = .04). "Disease too early",
      "advanced HCC", and "refusal by family members" were the most common reasons for
      rejection. CONCLUSION: Members of the Liver Transplant Program were more likely
      to refer suitable patients for transplant at the appropriate time. Better
      interaction between gastroenterologists inside and outside the transplant program
      would help to improve the timing of referrals for liver transplantation, and
      hence, patient survival.

PMID- 15561202
TI  - Do patients with acute liver failure have a better chance to receive liver
      grafting?
AB  - OBJECTIVE: Patients with acute hepatic failure (AHF) were always given first
      priority on the transplant waiting list. We investigated whether AHF patients
      will deprive other patients on the waiting list of the chance of liver
      transplantation (LTx). METHODS AND RESULTS: From January 1999 to March 2003, a
      total of 423 patients were on the transplant waiting list at the National Taiwan
      University Hospital. Sixty-five of the patients had AHF caused by hepatitis-B
      related disease (HBV, n = 52, 80%), Wilson disease (n = 3, 4.6%), drug-induced
      AHF (n = 3, 4.6%), and other causes (n = 7, 10.8%).Thirty-three patients died and
      16 survived by medical treatment. Two received LTx abroad and 14 underwent LTx at
      our hospital (7 living-related; 7 cadaver). A total of 140 patients died while
      waiting for a transplant during the period studied. Of them, 107 were among 358
      non-AHF patients (30%), and time-to-death interval was 133 +/- 175 days (median:
      62); 33 were among 65 AHF patients (51%); time to death was 19 +/- 28 days
      (median: 8). There were 35 cadaver donor livers available during the period; 28
      of 358 non-AHF patients (7.8%), and 7 of 65 AHF patients (10.7%) received
      cadaveric LTx. Their waiting time totaled 342 +/- 316 and 12 +/- 9 days,
      respectively (P < .0001). CONCLUSION: Most AHF patients died unless they received
      liver grafts. Even with a higher priority assigned to them, AHF patients still
      have little chance to get a cadaver donor liver in Taiwan, and non-AHF patients
      have an even slimmer chance. Therefore, we need to encourage liver donation from
      living-related donors.

PMID- 15561203
TI  - Inferior mesenteric venous left renal vein shunting for decompression of
      excessive portal hypertension in adult living related liver transplantation.
AB  - In the present study, we investigated the effect of decompression of excessive
      portal hypertension by inferior mesenteric venous (IMV) left renal vein shunting
      in 7 cirrhotic patients with esophago-gastric varices and 2 patients who
      underwent adult living related donor liver transplantation (ALRDLT). The portal
      pressure remarkably decreased after shunting in all patients with esophago
      gastric varices (388 +/- 42 mm H2O vs. 247 +/- 57 mm H2O; P < .05). It also
      decreased after a shunt operation in patients who had undergone liver
      transplantation. We report that the excessive shear stress by portal hypertension
      after small-for-size LRDLT induces a liver injury and the decompression of portal
      hypertension by splenic arterial ligation or splenectomy prevents postoperative
      liver injury following massive hepatectomy and small-for-size LRDLT. Our present
      studies suggested that IMV left renal vein shunting might prevent postoperative
      liver injury by partial decompression of excessive portal hypertension following
      small-for-size LRDLT.

PMID- 15561204
TI  - Living related liver transplantation for biliary atresia with portopulmonary
      hypertension: case report.
AB  - Portopulmonary hypertension is a complication of end-stage liver disease that
      adversely affects the outcome of liver transplantation (LT). We report a case of
      living related LT who developed severe pulmonary hypertension during and after
      LT. This 16-year-old girl suffered from biliary atresia, having undergone a
      portoenterostomy at 60 days of age, at the time of discovery of liver cirrhosis.
      She had been admitted to a local hospital several times for episodes of
      esophageal variceal bleeding. Neither dyspnea nor cyanosis was discerned until
      LT. Although pulmonary hypertension (PH) was disclosed by echocardiogram upon
      preoperative evaluation, we did not consider this a contraindication for LT,
      because the PH was mild. She underwent living LT from her father (graft
      volume/recipient body weight ratio: 0.99%). After induction of anesthesia for LT,
      a pulmonary flotation catheterization showed severe PH (>40 mm Hg). The pulmonary
      artery pressure continued to be elevated during surgery, although it was possible
      that her severe scoliosis affected the data. Hyperbilirubinemia was observed
      after LT, despite good liver function tests. On postoperative day 12, a portal
      vein thrombosis was detected requiring emergency thrombectomy and splenectomy.
      Her general condition worsened after the second surgery. She died due to
      cardiopulmonary failure. Autopsy showed marked hypertrophy of the right ventricle
      with intimal thickening in the pulmonary artery. In this case, the underestimated
      PH might have resulted in the unfortunate outcome. Before LT, PH should be
      carefully evaluated by measures including invasive assessment.

PMID- 15561205
TI  - Safety of hepatectomy for living donors as evaluated using asialoscintigraphy.
AB  - In the living donor operation, accurate estimation of hepatic functional reserve
      is essential. Technetium-99m-galactosyl-human serum albumin (GSA) is a liver
      scintigraphy agent that binds to asialoglycoprotein receptors. We evaluated the
      preoperative assessment of the safety of an elective hepatectomy using GSA liver
      scintigraphy in 152 patients. GSA scintigraphy was performed after intravenous
      injection of GSA. The maximal removal rate of GSA (GSA-Rmax) was calculated using
      a radiopharmacokinetic model. We determined the areas for resection
      preoperatively depending on the operative procedures and calculated the local GSA
      Rmax in the predicted residual liver (GSA-RL). A significant correlation was
      obtained between the GSA-Rmax and the 15-minute retention rate of indocyanine
      green. With sub- and monosegmentectomy, 2 patients had postoperative hepatic
      failure; in those 2 patients, the GSA-RL was 0.127 and 0.133, respectively, but
      these patients recovered well. Among those having di- and tri-segmentectomy, 5
      patients experienced postoperative hepatic failure, in all subjects the GSA-RL
      was <0.15. Two patients died of postoperative liver failure 1 to 2 months after
      the operation. We concluded that GSA-RL is useful to select the procedure for
      hepatectomy in living donors and that GSA-RL should be >0.15 (mg/min/50 kg body
      weight) to avoid postoperative hepatic failure.

PMID- 15561206
TI  - Eighteen living related liver transplants for Wilson's disease: a single-center.
AB  - The aim of this study was to review our experience with living related liver
      transplantation (LRLT) for Wilson's disease. From January 2001 to July 2003 LRLT
      were performed in 18 patients with Wilson's disease, seven of whom had neurologic
      complications. The mean age of the patients was 13.5 +/- 2.3 years (range 6 to
      20). Before transplantation all recipients displayed low serum ceruloplasmin
      levels (mean value = 118.4 +/- 32.6 mg/L). The serum ceruloplasmin levels
      increased to an average of 236.8 +/- 38.5 mg/L after LRLT at the latest
      evaluation, which ranged between 2 and 32 months after transplantation. A marked
      reduction in urinary copper excretion was observed in all recipients after
      transplantation. All recipients are alive and remain well. None have developed
      signs of recurrent Wilson's disease after a mean follow-up of 18.2 +/- 9.4 months
      (range 2 to 32 months). The donors were 17 mothers and one father of mean age
      34.0 +/- 3.0 years (range 30 to 45 years). The serum ceruloplasmin levels were
      within normal limits in all donors (mean 226 +/- 27.8 mg/L). Two donors had
      biliary leakage and percutaneous drainage Grafts included four right lobes
      without the hepatic middle vein and 14 left lobe grafts with the middle vein.
      LRLT is a curative procedure for Wilson's disease presenting with fulminant
      hepatic failure and the others with end-stage hepatic insufficiency. After liver
      transplantation, the serum ceruloplasmin level increases to the normal range,
      urinary copper excretion decreases, and neurological manifestations improve to
      various extents.

PMID- 15561207
TI  - Intraoperative blood lactate level as an early predictor of initial graft
      function in human living donor liver transplantation.
AB  - This study was performed to investigate whether intraoperative changes in blood
      lactate levels after hepatic allograft reperfusion reflect initial graft function
      in living donor liver transplantation (LDLT). PATIENTS AND METHODS: From 1994 to
      2003, 15 of LDLT cases were divided into two groups based on the intraoperative
      blood lactate levels. Group A consisted of seven recipients whose new liver
      grafts started to consume lactate immediately after portal perfusion. Group B
      consisted of the remaining eight recipients whose intraoperative blood lactate
      values showed no change or an elevation for 2 hours after graft
      revascularization. RESULTS: All Group A patients survived, whereas three out of
      eight patients in Group B died of infection and portal vein thrombosis within 3
      months after LDLT. There was no significant difference in preoperative donor and
      recipient laboratory data. The recipient age and body size in Group B were
      significantly higher than those in Group A, indicating that Group B consisted of
      small-for-size liver transplant cases. Serum total bilirubin concentrations in
      Group B were significantly higher than Group A from postoperative day 5 to 23,
      whereas postoperative liver enzyme levels and prothrombin time were similar
      between the two groups. CONCLUSION: The change in intraoperative blood lactate
      after hepatic allograft reperfusion served as an accurate predictor of initial
      graft function which was associated with graft size in human LDLT.

PMID- 15561208
TI  - Surgical complications and outcome of living related liver transplantation.
AB  - INTRODUCTION: Living donor liver transplantation (LDLT) is now widely performed
      for patients to resolve the critical shortage of organs from cadavers. Despite
      rapid implementation and expansion of the procedure, both outcome and
      complication analyses of LDLT are still incomplete. OBJECTIVES: To analyze the
      outcome of LDLT, with particular reference to complications of those in need of
      surgical or radiological intervention. METHODS: Forty-eight LDLTs performed at
      National Taiwan University Hospital between December 1997 and April 2003 were
      reviewed retrospectively. RESULTS: Forty-two (87.5%) patients survived the
      operation. The 1-year graft and patient survival rate was 81.5%. Seventeen of the
      48 LDLT patients had at least one postoperative complication, which needed
      surgical or radiological intervention. The complications included bile leakage (n
      = 3), biliary stricture (n = 4), internal bleeding (n = 7), intra-abdominal
      abscess (n = 2), liver abscess (n = 1), hepatic artery thrombosis (n = 2),
      duodenal ulcer bleeding (n = 1), jejunal perforation (n = 1), adhesion ileus (n =
      1), and intracranial hemorrhage (n = 1). Nine of the 17 patients with
      complications died. In contrast, only 2 of the other 31 patients died. Seven of
      the mortalities were related to the complications. All survivors received only
      one definite intervention early after the complications were diagnosed. However,
      the others received an average of 1.71 +/- 0.95 (0 to 3) interventions.
      CONCLUSIONS: Complications requiring surgical or radiological treatment caused
      major mortality of LDLT. Early and definite treatment of these complications is
      important to improve the patient's outcome.

PMID- 15561209
TI  - Hepatic vein anastomotic stricture after living donor liver transplantation.
AB  - This report discusses the pathophysiology of and therapeutic methods to address
      hepatic vein anastomotic stricture after living donor liver transplantation
      (LDLT). From 1994 to 2002, our 15 LDLTs using the lateral segments or left lobes
      included four recipients who experienced 28 occurrences of this complication
      after the operation. The period between LDLT and the first stricture was 4.0 +/-
      1.2 months. The age of the affected recipients (31.0 +/- 8.2 years) was
      significantly higher than that of the nonaffected patients (7.0 +/- 4.1 years, P
      < .05). Graft liver/standard liver volume ratio was 39.1% +/- 3.8% in the former
      and 77.9% +/- 12.7% in the latter cases (P < .05). Initial symptoms of stricture
      were ascites (42.9%), abdominal distention (42.9%), liver enzyme elevation
      (10.7%), and gastrointestinal bleeding (3.6%). In addition, 14 of 28 stricture
      cases (50%) showed increased blood trough levels of tacrolimus. Doppler
      ultrasonography was used for diagnosis, and balloon dilatations performed in all
      stricture patients, thereby hepatic significantly reducing venous blood pressure
      from 33.5 +/- 1.7 to 20.3 +/- 1.5 cmH2O. All patients finally resolved the
      strictures after several treatments. The stricture after LDLT was associated with
      small-for-size grafts, suggesting that liver regeneration may lead to anatomical
      changes and strictures. Since tacrolimus is metabolized by the liver, its blood
      trough level is one initial symptoms of stricture. Balloon dilatation was useful
      and safe as the treatment, while problems have been reported after stent
      insertion in the hepatic vein.

PMID- 15561210
TI  - Factors affecting graft survival after living donor liver transplantation.
AB  - Living donor liver transplantation (LDLT) has been considered as an alternative
      option to resolve the shortage of cadaveric donor organs, despite the ethical
      aspects of the donor procedure. The objective of this study was to analyze the
      risk factors affecting graft survival in LDLT. From June 1996 to December 2002,
      141 patients who underwent LDLT were retrospectively analyzed. Graft survival
      rates were 82.5%, 80%, 77.3%, and 77.3% at 6 months, 1 year, 3 years, and 5
      years, respectively. The factors influencing graft survival in univariate
      analysis were graft-to-recipient body weight ratio (GRWR) less than 0.8% (P =
      .0009), intraoperative transfusion of more than six packed RBC units in addition
      to the use of cell saver amounts (P = .0001), left lobe grafts in adults causing
      small-for-size situations (P = .0135), and donor age (P = .0472). The
      multivariate analysis demonstrated that GRWR less than 0.8% (P = .002) and
      intraoperative transfusion of more than six packed RBC units (P = .014) were
      independent factors that decreased graft survival rates. The graft selection of
      greater than 0.8% of GRWR and reduction of intraoperative RBC transfusion improve
      graft survival.

PMID- 15561211
TI  - Functional hepatic regeneration following hepatectomy using galactosyl-human
      serum albumin liver scintigraphy.
AB  - In extended hepatectomy and liver transplantation, accurate estimation of
      functional hepatic regeneration is more important than volumetric regeneration.
      We investigated the usefulness of measuring the functional hepatic volume by 99m
      technetium galactosyl-human serum albumin scintigraphy (GSA). Extended
      hepatectomy was performed in 32 patients. These patients were divided into
      subgroups with or without chronic hepatitis or cirrhosis. Functional hepatic
      volume GSA scintigraphy (GSA-LV) and determination of hepatic volume by CT (CT
      LV) measurements were performed preoperatively, at 2 and 4 weeks and at 3 and 6
      months after surgery. The preoperative GSA-LV values were significantly
      correlated with the hepatocyte volume and the 15-minute retention rate of
      indocyanine green (ICGR15). Similarly, the hepatocyte volume correlated well with
      the CT-LV and ICGR15. However, the CT-LV correlated only with the ICGR15.
      Recovery of the GSA-LV was delayed, and about 90% of the volumetric and
      functional regeneration was observed within 6 months after the hepatectomy. In
      contrast, the CT-LV in patients with normal liver remnants returned to
      approximately 90% of the initial volume within 1 month after the hepatectomy,
      whereas patients with injured livers regeneration showed gradual recovery to
      approximately 80% of the preoperative value by 6 months after hepatectomy. We
      conclude that measurement of functional hepatic volume using the GSA-LV is useful
      to evaluate hepatic function based on hepatocyte volume.

PMID- 15561212
TI  - Interpostion vein graft in living donor liver transplantation.
AB  - In adult-to-adult living donor liver transplantation (LDLT), right lobe grafts
      without a middle hepatic vein can cause hepatic congestion and disturbance of
      venous drainage. To solve this problem, various types of interposition vein graft
      have been used. OBJECTIVES: We used various types of interposition vein grafts
      for drainage of the paramedian portion of the right lobe in living donor liver
      transplantation. METHODS: From June 1996 to June 2003, 37 of 176 patients (128
      adults, 48 pediatric) who underwent LDLT received vein grafts for drainage of
      segments V, VIII, or the inferior portion of the right lobe. RESULTS: In 36 adult
      cases the reconstruction included the inferior mesenteric vein of the donor (n =
      14); cadaveric iliac vein stored at cold (4 degrees C) temperature (n = 5);
      cryopreserved (-180 degrees C) cadaveric iliac vein (n = 10); cryopreserved
      cadaveric iliac artery (n = 1 case); donor ovarian vein (n = 1); recipient
      umbilical vein (n = 3); recipient saphenous vein (n = 1); recipient left portal
      vein (n = 1); recipient left hepatic vein (n = 1). In a pediatric case with
      malignant hemangioendothelioma that encased and compressed the inferior vena
      cava, we used an interposition vein graft to replace the inferior vena cava.
      CONCLUSION: Various types of interposition vein grafts can be used in living
      donor liver transplantation. Cryopreserved cadaveric iliac vein and artery are
      useful to solve these drainage problems.

PMID- 15561213
TI  - Indications for hepatic vein reconstruction in living donor liver transplantation
      of right liver grafts.
AB  - BACKGROUND: To overcome problems arising from a graft of insufficient size, right
      liver grafts have been used extensively for adult-to-adult living donor liver
      transplantation (LDLT). However, there are reports of severe congestion in the
      anterior segment of the graft after transplantation. CASE REPORTS: Right liver
      transplantation without the middle hepatic vein was performed in six cases. In
      the second and third cases, the inferior right hepatic vein was reconstructed
      because it was thick (whereas the middle hepatic vein was not). Abdominal CT
      revealed congestive infarction of the anterior segment in the second case and of
      the posterior segment in the third. It was suspected that the former resulted
      from the lack of an middle hepatic vein, and the latter from obstruction of the
      reconstructed inferior right hepatic vein. Both patients died without improvement
      in liver function. Accordingly, in the fifth case, the middle hepatic vein was
      reconstructed. The postoperative course of this case was uneventful. Doppler
      ultrasonography showed profuse blood flow in the interposition graft. In the
      sixth case, the middle hepatic vein was not reconstructed because of technical
      difficulties. Although abdominal CT showed a congestive area in the anterior
      segment, the patient recovered uneventfully, probably because the volume of
      functional graft was sufficient even without the congestive area. CONCLUSION:
      When the color becomes dark in more than half of the surface of the anterior
      segment following clamping of middle hepatic vein tributaries and the hepatic
      artery, the middle hepatic vein should be reconstructed. When the diameter of the
      inferior right hepatic vein is more than 5 mm, its reconstruction is also
      recommended.

PMID- 15561214
TI  - Portal vein arterialization for liver transplantation with extensive
      portomesenteric vein thrombosis: a case report.
AB  - We report herein a case of extensive thrombosis of portal venous system including
      mesenteric vein in a 70-year-old man who suffered from end-stage post-hepatitis C
      cirrhosis and who underwent orthotopic liver transplantation. There was no way to
      divert portal blood flow to the new liver because such an extensive thrombosis of
      portomesenteric venous system. There are some case reports of portocaval
      hemitransposition with some success but high mortality. We decided to arterialize
      the portal vein of the liver allograft with the recipient hepatic artery and the
      donor hepatic artery was anastomosed to the supraceliac aorta. He recovered
      slowly from the operation. At 1 year after the transplantation, he is doing well
      with perfect liver function tests. This case challenges our belief that portal
      blood flow is essential for the liver because of hepatotrophic factors.

PMID- 15561215
TI  - Successful case of adult ABO-incompatible liver transplantation: beneficial
      effects of intrahepatic artery infusion therapy: a case report.
AB  - BACKGROUND: In Japan ABO-incompatible liver transplantation has been done on >100
      occasions up to 2003. However, <30% are cases involving adults. The difficultly
      of ABO-incompatible liver transplantation is associated with the high frequency
      of humoral rejection and local disseminated intravascular coagulation (DIC),
      leading to many postoperative complications. We report a successful case of adult
      ABO-incompatible liver transplantation with the use of an intrahepatic artery
      infusion. METHODS: A 36-year-old man with Wilson disease, underwent living donor
      liver transplantation from an ABO-incompatible donor. The immunosuppressive
      therapy included multiple perioperative plasmaphereses, splenectomy, and
      treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and
      blood level of tacrolimus were the same as in ABO-compatible cases. In addition
      to these therapies, we administered an intrahepatic arterial infusion with
      prostaglandin (PG) E1 alone. RESULTS: After perioperative plasmapheresis and
      cyclophosphamide, antidonor blood group antibody titers remained undiluted and
      without vascular complications throughout the postoperative course, but there was
      a tendency for bleeding that continued for 10 days after transplantation. On
      postoperative day 10, a reexploration was performed for intraabdominal bleeding.
      During another operation on postoperative day 59 a biloma was found and drained.
      The patient has now survived for 120 days after transplantation with normal liver
      function. CONCLUSIONS: Beneficial effect of intrahepatic artery infusion with
      PGE1 seems to be useful in adult ABO-incompatible liver transplantation.

PMID- 15561216
TI  - Small-for-size graft in adult living-donor liver transplantation.
AB  - In the era of living donor liver transplantation (LDLT), graft size is related to
      recipient prognosis. This study was performed to compare the clinical outcomes
      according to the graft-to-recipient weight ratio (GRWR) in adult LDLT. Seventy
      nine adult patients who had undergone LDLT between June 1997 and June 2002 were
      retrospectively analyzed. The patients were divided into two groups according to
      the GRWR (group I, GRWR < 0.8%, n = 11; group II, GRWR > or = 0.8%, n = 68). The
      mean follow-up period was 19.4 (range 1 to 48) months. The recipients were 62 men
      (78.5%) and 17 women (21.5%) of mean age 45.2 (range 18 to 63) years. The overall
      patient survival rates were 74.7% at 1 year and 70.7% at 2 years. The patient
      survival rate in group I was 54.6% at 1 year and 40.9% at 2 years, whereas that
      in group II was 77.9% at 1 year and 75.3% at 2 years, showing a significant
      difference (P = .03). There were no significant differences in postoperative
      total bilirubin, transaminase enzyme level, prothrombin time (INR), portal vein
      flow on Doppler sonography, amount of ascites through the drain, complications,
      or acute rejection rates between the two groups. In conclusion, the minimum
      acceptable graft size in an adult-to-adult LDLT is GRWR of 0.8%. This study
      suggests that careful postoperative management and/or technical modifications
      during surgery are necessary, because small-for-size grafts (GRWR < 0.8%) result
      in lower patient survival rates.

PMID- 15561217
TI  - Critical graft size and functional recovery in living donor liver
      transplantation.
AB  - With a high prevalence of chronic hepatitis B and a low cadaveric organ donation
      rate, living donor liver transplantation (LDLT) remains the only option for many
      patients in Hong Kong. In such cases, the liver graft volume is smaller owing to
      a partial liver graft; therefore, a problem of small-for-size grafts often
      occurs. Between September 1999 and April 2003, 25 cadaveric, 16 living related,
      and 1 auto-LTs were performed at our center. The outcomes of LDLT were analyzed
      to assess the critical graft size and functional recovery. Among the 16 LDLT
      recipients (mean age, 44.4 +/- 14.4 years; mean weight, 61.9 +/- 11.4 kg), 1
      patient received a graft from a donor left lobe (weight, 400 g) in an auxillary
      partial orthotopic LT (APOLT), 12 received right lobes, and 3 received left
      lobes. Besides the APOLT case, the overall graft/recipient weight ratio (GRWR)
      for the 15 LDLTs was 1.11 (0.76 to 1.75). The GRWR in the 25 cadaveric LTs was
      1.92 (1.05 to 3.69) (P < .001). Among the 12 successful LDLTs, there were 5
      (41.7%) cases of small-for-size graft syndrome: 3 of 3 (100%) in GRWR < or =
      0.8%; 5 of 6 (83.3%) in GRWR < 1%; and 0 of 6 with GRWR > 1%. The initial post-LT
      graft function parameters were significantly higher among the LDLT group:
      International normalized ratio (INR), 1.42 vs 1.24, P = .03; alanine
      aminotransferase (ALT, 387 vs 201 IU/L, P = .005, and bilirubin, 170 vs 48
      micromol/L, P < .001 as compared to the cadaveric transplant group). Small-for
      size graft syndrome can be avoided if GRWR > 1%, but often occurs when GRWR <
      0.8%. Graft function in LDLT recovers more slowly than in cadaveric liver
      transplant.

PMID- 15561218
TI  - Primary immunosuppression regimen of rapid steroid withdrawal after living
      related liver transplantation: a single-center experience.
AB  - AIM: Corticosteroids have been considered the mainstay of immunosuppressive
      therapy after liver transplantation. However, the side effects of long-term
      steroid use such as diabetes, infections, and bone disease, including growth
      retardation in children, are serious problems. Our immunosuppression regimen
      includes FK506 and steroid withdrawal by 30 days after transplantation. The aim
      of this study was to determine the outcomes of liver transplant, using this
      immunosuppressive regimen. PATIENTS: Fifteen primary liver transplant recipients
      were performed between January 1994 and May 2003 and data were reviewed
      retrospectively. Eight pediatric and four adult recipients, who had survived more
      than 3 months after transplantation, were included in this sample. The
      immunosuppressive regimen consisted of FK 506 (Prograf), initially at doses of
      0.03 mg/kg, with dose adjustments to achieve daily trough levels of approximately
      10 to 12 ng/mL, and predonisone, initially at 4 mg/kg/d, with a taper and
      cessation by 30 days when the graft was stable. RESULTS: All recipients were
      successfully withdrawn by 30 days. Acute rejection episodes occurred in three
      patients, no patient was diagnosed with chronic rejection. The acute rejection
      free rate at 5 year was 74.1%. No recipient had diabetes, serious infections or
      bone disease. CONCLUSION: Our primary immunosuppressive regimen of rapid steroid
      withdrawal is safe with regard to acute and chronic rejection with benefits upon
      steroid-related side effects.

PMID- 15561219
TI  - Case of living donor liver transplantation in a patient with biliary atresia
      combined with situs inversus.
AB  - Until recently, situs inversus was considered to be an absolute contraindication
      for liver transplantation. However, recent reports have suggested that situs
      inversus should not be considered a contraindication. This study presents a
      successful living donor liver transplantation performed in a 4-month-old male
      infant with biliary atresia and situs inversus. The surgical findings revealed
      abdominal situs inversus with polysplenia and an absent retrohepatic inferior
      vena cava and intestinal malrotation.

PMID- 15561220
TI  - The survival and value of liver transplantation for liver carcinoma: a single
      center experience.
AB  - Liver transplantation for liver carcinoma with cirrhosis is a treatment still in
      dispute. The objectives were to summarize the survival and cost of 50 liver
      transplant cases performed for liver carcinoma over nearly 3 years. METHODS: We
      performed 138 liver transplants from January 1999 to February 2002. There were 50
      cases (36.2%) of liver carcinoma with HBV cirrhosis, which were divided into
      three stages based on the tumor pathology: Stage 1 cases showed a single mass (<
      or = 5 cm), 4 cases; Stage 2, a single mass > 5 cm or intrahepatic multiple
      masses without PV cancer embolus, 32 cases; and Stage 3: tumor invasion of the PV
      or perihepatic lymph nodes or organs, 14 cases. All patients received three to
      six courses of chemotherapy postoperatively. RESULTS: All four cases of stage 1
      survived > 1 year; one of them is at 3 years with good liver function and tumor
      free. The mean half-year medical cost was $27.100 +/- 108 in stage 1. The half
      year survival and medical costs were 62.5% and $31,500 +/- 260 in stage 2 and
      15.0% and $35,500 +/- 134 in stage 3. CONCLUSION: Liver transplantation is an
      effective treatment for early-stage liver carcinoma, that achieves good medical
      and economic results, but should be limited to advanced liver cancer.

PMID- 15561221
TI  - Multimodality tumor control and living donor transplantation for unresectable
      hepatocellular carcinoma.
AB  - Liver transplantation (LT) is an acceptable mode of treatment for selected
      patients with unresectable hepatocellular carcinoma (HCC). However, due to the
      scarcity of cadaveric donor organs, it is considered desirable for patients to
      opt for living donor liver transplantation (LDLT) or, for those not being
      transplanted soon, to have some form of tumor control therapy. Such an approach
      in our program is analyzed and reported. At our institution, 42 LTs were
      performed between October 1999 and April 2003. Of these, 18 recipients (15 men, 3
      women) had 27 HCC. The average number and size of HCC was 1.59 (1 to 4) and 2.31
      (0.2 to 6.5) cm, respectively. Thirteen (72%) patients were transplanted
      primarily for the HCC, whereas five (28%) others were incidental HCC cases. Seven
      patients (5 LRLT, 2 cadaveric LT) were transplanted soon after listing, and thus
      did not require tumor control therapy. Six patients waited for 11 (6 to 19)
      months before LT. Three patients underwent microwave coagulation therapy, and one
      had additional alcohol injections. One patient received the novel PIAF
      (cisplatin, interferon, adriamycin, and 5-FU) chemotherapy regimen followed by
      selective internal irradiation (SIR) treatment. One patient received conformal
      radiation therapy and another received SIR treatment before LT. Besides 2
      postoperative deaths, the remaining 16 patients have been well, with a mean
      follow-up of 20.4 (3.6 to 41.2) months. In conclusion, for patients with
      unresectable HCC, in areas with poor cadaveric donor rate, living donation should
      be the first option. If a suitable live donor is not available, aggressive
      multimodality therapy is recommended while waiting for cadaveric LT.

PMID- 15561222
TI  - Can we expand the Milan criteria for hepatocellular carcinoma in living donor
      liver transplantation?
AB  - INTRODUCTION: The Milan criteria, namely, tumors 5 cm or less in diameter in
      patients with single hepatocellular carcinoma (HCC), no more than 3 tumor
      nodules, and each 3 cm or less in diameter in patients with multiple tumors, are
      accepted for cadaveric liver allocation. However, in living donor liver
      transplantation (LDLT), graft donation may only depend on the donor's intention.
      The aim of this study was to elucidate the feasibility of Milan criteria in LDLT.
      MATERIALS AND METHODS: From January 2001 to December 2002, 46 cases of liver
      transplantation (LT) for HCC included 5 hospital mortalities and 3 cadaveric
      transplantations, all of which were excluded. We classified the patients into
      Group I cases that met the Milan criteria and Group II cases that did not meet
      the Milan criteria. The analyses examined tumor-related risk factors affecting
      recurrence and survival, such as tumor size, number of tumor nodules, and
      presence of microvascular and macrovascular invasion. RESULTS: Twenty-one cases
      belonged to Group I and 17 to Group II. There was no significant difference in
      the recurrence or survival rates between Groups I and II. The risk factors
      affecting recurrence were macrovascular invasion and tumor size (5 cm). The
      number of tumor nodules and microvascular invasion did not appear to affect
      recurrence. The risk factor affecting survival was macrovascular invasion.
      CONCLUSION: We suggest that in selected cases the Milan criteria could be
      extended to increase the number of tumor nodules as long as the HCC were small
      and did not macrovascular invasion.

PMID- 15561223
TI  - Liver transplantation for patients with hepatocellular carcinoma.
AB  - BACKGROUND: Liver transplantation (LT) has been advocated as a salvage treatment
      for unresectable hepatocellular carcinoma (HCC). Selection criteria still need to
      be developed in Taiwan. OBJECTIVES: The purpose of our study was to assess the
      clinical findings and outcome of cirrhotic patients with HCC undergoing liver
      transplantation. METHODS: Our study consisted of 13 HCC patients who underwent
      liver transplantation during October 1996 to March 2003. The medical records and
      pathologic reports were analyzed retrospectively. RESULTS: Overall survival rates
      at 1 and 3 years were 86% and 61%, respectively. HCC recurrences occurred in
      three patients, one of whom is still alive with HCC recurrence 2 years after LT.
      The other two patients died of HCC recurrence 1 and 2 years after LT,
      respectively. Pretransplant alpha-fetoprotein (AFP) levels of >200 ng/mL were
      noted in all three patients with HCC recurrence. In contrast, only one of the ten
      patients without HCC recurrence had pretransplant AFP >200 ng/mL (P = .003). Four
      patients did not meet Milan criteria, two of whom had HCC recurrence. However,
      the other two patients with microscopic vascular invasion survived and were free
      of HCC. The only one patient, who had histologic grade 4 HCC, died of recurrence,
      although his tumor was AJCC stage 1. CONCLUSIONS: High AFP level is a risk factor
      for HCC recurrence after LT. In addition to Milan criteria, histologic tumor
      grading should be considered in patient selection. Microscopic vascular invasion
      may not affect the outcome of the patients with early HCC.

PMID- 15561224
TI  - Clinicopathological features of incidental hepatocellular carcinoma in liver
      transplantation.
AB  - The incidence of detecting hepatocellular carcinoma (HCC) in a removed recipient
      liver after a liver transplant is not rare. The clinical features are expected to
      be different from the preoperatively diagnosed HCC. The aim of this study was to
      evaluate the clinicopathological features of incidental HCC. This study
      retrospectively analyzed five cases of incidental HCC among 51 liver transplant
      cases of HCC operated from September 1996 to February 2002. The proportion of an
      incidental HCC was 9.8%. The mean age was 46.2 years with a higher prevalence in
      may (80%, four cases). The alpha-fetoprotein level was normal or mildly elevated.
      HBsAg was positive in all cases. Imaging studies revealed regenerative or
      dysplastic nodules, or no specific lesion. The pathological findings demonstrated
      a mean size of 1.16 cm, multiplicity in three cases (60%), no microvascular
      invasion, and Edmonson grade I (60%) and II (40%). There was no recurrence of the
      HCC. However, two patients died due to an intracranial hemorrhage and a graft
      failure, respectively. In conclusion, incidentally found HCC showed less invasive
      pathological features and a better prognosis.

PMID- 15561225
TI  - The significance of transarterial embolization for advanced hepatocellular
      carcinoma in liver transplantation.
AB  - INTRODUCTION: Transarterial embolization (TAE) is the treatment of choice for
      advanced HCC to control or even induce tumor shrinkage. The aim of this study was
      to evaluate the effect of pretransplantation TAE for treatment of advanced HCC.
      MATERIAL AND METHODS: From 1996 to 2002, we studied 12 cirrhotic patients with
      HCC, including six who met and six who exceeded the Milan criteria. All patients
      had sufficient hepatic function to undergo TAE. Liver transplantations were
      performed subsequently and they were followed prospectively for a median of 22
      months (range = 12 to 53 months). RESULTS: The explanted livers from the 12
      patients who had undergone TAE were noted to have extensive tumor necrosis. The
      pathological specimens at LT showed downstaging of the HCC, which allowed those
      six patients to meet the Milan criteria. The overall 1- and 2-year survival rates
      were 92% and 73%, respectively. The overall 1- and 2-year disease-free survival
      rates were 92% and 73%, respectively. One death unrelated to liver disease at 2
      years after LT was noted in the downgraded group. One patient of the initially
      eligible group developed lung metastasis at 6 months and died at 12 months after
      LT. CONCLUSION: TAE is effective to downstage advanced HCC and reduce the dropout
      rate on the LT waiting list. Pre-LT TAE may be considered as a better therapeutic
      strategy for patients with advanced HCC.

PMID- 15561226
TI  - Living related donor liver transplantation for primary sclerosing cholangitis
      with hepatocellular carcinoma and Crohn's disease: a case report.
AB  - INTRODUCTION: Primary sclerosing cholangitis (PSC) is a premalignant condition
      associated with a risk of developing cholangiocarcinoma in 10% to 20% of
      patients. However, the prevalence of hepatocellular carcinoma (HCC) in patients
      with PSC is estimated to be only 2%. In addition, PSC often occurs in association
      with inflammatory bowel disease. Ulcerative colitis occurs in 60% of PSC patients
      and Crohn's disease occurs in about 10%. We diagnosed a patient as having PSC
      with HCC and concomitant Crohn's disease prior to living related donor liver
      transplantation (LRDLT). PATIENTS AND METHODS: A 63-year-old woman was diagnosed
      as having PSC with solitary HCC. Preoperative liver condition was Child-Pugh
      grade C. Colonoscopic findings showed an active longitudinal ulcer in the
      terminal ileum and clinically diagnosed Crohn's disease. The medical treatment
      was 5'-aminosalicylates. She received a left lobe graft from her daughter. The
      immunosuppressants were tacrolimus and azathioprine, which was changed to
      predonisolone because of leukopenia and moderate acute cellular rejection, after
      which the postoperative course was uneventful. Colonoscopic findings revealed
      disappearance of the longitudinal ulcer in the terminal ileum at 15 months after
      LRDLT. There was no evidence of PSC or HCC recurrence. CONCLUSIONS: Generally,
      PSC with HCC is rare with a poor prognosis; however, LRDLT may be a treatments
      option although the patient with PSC had a combined HCC. Moreover,
      aminosalicylates together with the immunosuppressants may be effective for the
      clinical management of concomitant Crohn's disease.

PMID- 15561227
TI  - Surveillance of perioperative infections after adult living donor liver
      transplantation.
AB  - AIM: This study was conducted to clarify the management of perioperative
      infectious complications after adult living donor liver transplantation (LDLT).
      PATIENTS AND METHODS: Fourteen adult LDLT patients were enrolled in this study.
      We examined the occurrence of infectious complications in these cases and the
      relationships of infectious complications to UNOS status and MELD score.
      Surveillance culture and immunoserologic analyses were performed. From the
      results of these analyses, we made a diagram of infection surveillance using a
      matrix of time and sampling site. Using the diagram, we chose sensitive
      antibiotics as soon as possible. RESULTS: The infection site and its pathogen
      were able to be detected in four (28.5%) patients, all of whom had MRSA
      infections, together with lung aspergillosis in one case, pseudomonas pneumonia
      in another, and both in another. Two patients died of lung aspergillosis.
      Bacteria detected in the airway tended to spread to other sites during the
      postoperative period. In all four patients in whom infectious diseases were
      detected, and in a fifth patient in whom the site of infection was not known, the
      UNOS status was 1. The MELD score was calculated in eight patients, six of whom
      had high MELD scores (>20). CONCLUSION: Most cases were manageable by choosing
      and changing antibiotics and antifungal drugs according to the results of
      surveillance cultures twice a week. However, aspergillosis had an extremely poor
      prognosis. Patients with a high MELD score or low UNOS status, or both, showed
      poor prognosis; and in them, multiple drug resistance bacteria caused severe
      perioperative infectious complications.

PMID- 15561228
TI  - Impact of severe acute respiratory syndrome on liver transplantation service.
AB  - Severe acute respiratory syndrome (SARS) struck 1755 patients in Hong Kong and
      developed into a global health crisis. Although the World Health Organization and
      national health authorities are sparing no effort to contain the disease and to
      find a cure for the potentially deadly infection, SARS has an impact on our liver
      transplantation (LTx) program. Before the SARS outbreak, an average of 1 LTx was
      performed per month in our center. For 6 months since the outbreak, there had
      been no LTx performed. The intensive care unit had to be dedicated to patients
      with SARS. Two of the LTx team members were struck by SARS. A survey conducted
      among LTx recipients and their family members (n = 45) demonstrated symptoms of
      anxiety and stress in all. Some LTx recipients were treated at the Emergency
      Department for suspected SARS, which were later confirmed to be false alarms.
      Many LTx patients were too frightened to come back for follow-up. A new strain of
      coronavirus was identified as the causative agent. The origin of this virus is
      uncertain but the probability of zoonoses is being seriously discussed. Not only
      are immunosuppressed patients exposed to higher risk of infection, but also the
      waiting list mortality is also expected to increase. The SARS outbreak has
      demonstrated the vulnerability of an organ transplantation service and reminds us
      of the fearful possibility of zoonoses in future xeno-transplantation.

PMID- 15561229
TI  - Rapid progressive hepatitis C after liver transplantation: a case report.
AB  - A 56-year-old man on hemodialysis for 3 years because of chronic renal failure
      underwent living related donor liver transplantation (LRDLT) and splenectomy
      using the right hepatic lobe for liver cirrhosis type C (genotype 1b) with
      hepatocellular carcinoma. At 69 postoperative days (POD), he displayed a high
      fever and his blood transaminase and total bilirubin were increased. Based on
      finding in his liver biopsy, we diagnosed rapid recurrence of progressive
      hepatitis C after LRDLT, so we administered IFNbeta. Thereafter his liver
      function returned to normal and his HCV-mRNA decreased to 1200 kcopy/mL. We
      inferred that hemodialysis and splenectomy decreased his immunity, allowing
      rapidly progressive hepatitis C recurrence after LRDLT.

PMID- 15561230
TI  - A case of laryngeal posttransplantation lymphoproliferative disease.
AB  - The development of posttransplant lymphoproliferative disease (PTLD) is strongly
      linked to infection with the Epstein-Barr virus (EBV), immunosuppression-state,
      the type of allograft, and EBV-seronegativity. A 18-month-old girl who had
      undergone living donor liver transplantation using the left lateral segment from
      her father was treated with tacrolimus and corticosteroid as an immunosuppressant
      regimen. She was readmitted 3 months after the transplant to evaluate the
      etiology of dyspnea and abdominal fullness as well as a decreased urine volume.
      She was diagnosed as an anastomotic stenosis of the hepatic vein for which she
      underwent balloon angioplasty. The treatment was repeated at postoperative month
      5, 8, and 11. As postoperative 6 months, the result of the serological EBV-CA
      (IgG/IgM) was positive. In postoperative month 10, the EBV PCR serologic test
      become positive, and a laryngeal biopsy revealed PTLD. She was treated with
      acyclovir and gangyclovir as well as reduced immunosuppression. We report herein
      a rare case of laryngeal PTLD in a patient who had undergone living donor liver
      transplant with paternal allograft.

PMID- 15561231
TI  - Posttransplantation lymphoproliferative disorder in pediatric liver
      transplantation.
AB  - INTRODUCTION: The aim of this study was to evaluate the clinical features of risk
      factors for posttransplantation lymphoproliferative disorder (PTLD) in pediatric
      liver transplantation. MATERIALS AND METHODS: Between June 1996 and June 2002,
      among 41 pediatric patients who underwent liver transplantation, 7 died in the
      postoperative period. Thirty-five patients, including 1 patient who died of PTLD,
      were reviewed. Based on the serology results, patients were divided into a high
      risk group (EBV-naive recipients of EBV-positive grafts) and a low-risk group
      (patients other than those in the high-risk group). RESULTS: Five of 41 patients
      (12.2%) developed PTLD. All of them belonged to the high-risk group. The
      incidence of PTLD in the high-risk group was 31.3% (5 of 16). The mean duration
      between operation and diagnosis for PTLD was 9.8 months. Primary EBV infection
      developed at a median of 6 months after transplantation. Three of 5 patients
      developed rejection before the diagnosis of PTLD. One patient was diagnosed with
      laryngeal and gastrointestinal PTLD, whereas the other 4 had gastrointestinal
      PTLD. They experienced the following symptoms and signs: anemia (100%),
      hypoalbuminemia (100%), fever (80%), diarrhea (80%), gastrointestinal bleeding
      (80%), and anorexia (60%). CONCLUSION: The common features of PTLD development
      were as follows: (1) EBV-positive donors placed into EBV-naive recipients, (2)
      primary EBV infection approximately 6 months after transplantation, (3) young
      age, 1 year old at operation, and (4) requirement for intensive
      posttransplantation immunosuppression.

PMID- 15561232
TI  - Absence of impact of donor hepatic steatosis and posttransplantation lamivudine
      resistance in a patient with chronic hepatitis B.
AB  - A patient with chronic hepatitis B underwent liver transplantation for end-stage
      cirrhosis. The donor liver graft had moderate steatosis and fibrosis. He was
      placed on lamivudine for hepatitis B prophylaxis but developed viral relapse due
      to emergence of a lamivudine-resistant mutant at week 72 posttransplantation.
      Results of liver biochemistry were normal liver histology revealed minimal
      steatosis and inflammation at weeks 151 and 128, respectively. This report
      illustrates that the use of a steatotic donor liver and the emergence of
      lamivudine resistance posttransplantation are not necessarily associated with
      significant graft damage. A marginal donor graft can be considered due to the
      donor shortage. Lamivudine monoprophylaxis for hepatitis B virus-related liver
      diseases post liver transplantation can be used in areas where hepatitis B
      immunoglobulin is not affordable.

PMID- 15561233
TI  - Prevention of de novo hepatitis B infection from HbcAb-positive donors in living
      donor liver transplantation.
AB  - Hepatitis B virus (HBV) prophylaxis is necessary to prevent de novo hepatitis B
      infection from HbcAb-positive donors. However, which protocol is more effective
      is somewhat controversial. Also, it is uncertain whether it is necessary to
      administer HBV prophylaxis for HbsAb-positive recipients. This study attempted to
      determine whether it is necessary to administer HBV prophylaxis for HbsAb
      positive patients and to evaluate the efficacy of an HBIG monotherapy protocol.
      From May 1996 to July 2001, among 128 donors examined for HbcAb, 58 donors
      (45.3%) were HbcAb-positive. Eighteen HbcAb-positive grafts were transplanted to
      HbsAg-negative recipients. The 4 patients who died of unrelated causes were
      excluded from this study. Of 14 study cases, 12 recipients were HbsAb-positive,
      and 2 were HbsAb-naive. Prior to late 1998, we used HBV vaccination only for de
      novo infection prophylaxis. However, starting from December 1998, HBIG was
      administered from the time of the liver transplantation regardless of HBsAb
      positivity. The overall rate of de novo HBV infections from HbcAb-positive donors
      was 21.4% (3 of 14). All 3 recipients without HBIG prophylaxis presented with de
      novo HBV infections. Two were HbsAb-positive preoperatively. No de novo HBV
      infections occurred among recipients with HBIG prophylaxis. Therefore, it is
      essential to administer HBV prophylaxis even for vaccinated HbsAb-positive
      patients. HBIG monotherapy is effective to prevent de novo hepatitis B infections
      from HbcAb-positive donors in living donor liver transplantation.

PMID- 15561234
TI  - Adefovir dipivoxil as the rescue therapy for lamivudine-resistant hepatitis B
      post liver transplant.
AB  - INTRODUCTION: Complications of hepatitis B virus (HBV) infection are among the
      most common indications for liver transplant in many parts of Asia. However, none
      of the current posttransplant hepatitis B prophylaxis strategies, namely,
      lamivudine, hepatitis B immunoglobulin monotherapy, or combination therapy, is
      ideal. Our aim was to evaluate the use of adefovir dipivoxil (ADV) as a rescue
      therapy for posttransplant HBV patients who developed lamivudine resistance.
      METHODS: Twenty-two consecutive patients with HBV-related liver disease, who
      underwent first liver transplants from 1995 to 2002, received HBV prophylaxis
      with indefinite lamivudine with substitution of ADV for patients who developed
      drug resistance and clinical deterioration, defined as persistent elevation of
      transaminases or histologic deterioration. RESULTS: Sixteen patients (73%) were
      alive at their last follow-up and six (38%) had developed hepatitis B recurrence
      at a median of 46 (range 9 to 74) months posttransplant. Two with persistently
      normal transaminases and normal liver histology at 3 and 42 months postrecurrence
      have been continued on lamivudine. Four showed clinical deterioration and
      received ADV for a median of 24 months; all displayed normalization of
      transaminases and a 2 to 5 log drop in HBV DNA titers. Three had paired biopsies
      before and after substitution of ADV with two showing improvement and one stable
      appearance. The median serum creatinine value increased slightly from 126 to 138
      micromol/L (P = 0.72). CONCLUSION: ADV is an effective rescue therapy for
      patients with lamivudine-resistant hepatitis B post-liver transplant. Further
      studies are needed to ascertain the optimal posttransplant hepatitis B
      prophylaxis.

PMID- 15561235
TI  - Prevention of hepatitis B virus reinfection after orthotopic liver
      transplantation.
AB  - OBJECTIVE: We discuss the prevention of hepatitis B virus reinfection following
      orthotopic liver transplantation. METHODS: Sixty-eight cases of chronic fulminant
      hepatitis B, the end stage of liver cirrhosis and liver carcinoma complicated
      with HBV cirrhosis, were given antiviral drugs pre- and posttransplantation to
      prevent hepatitis B virus reinfection. Lamivudine was administered to two cases
      and lamivudine + HBIG to 63 cases. Adefovir + HBIG was administered to three
      cases. The serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical
      examinations were performed. RESULTS: One of two cases given lamivudine developed
      reinfection with serum HBSAg, HbeAb, HBcAb, HBV DNA, and positive and liver
      biopsy immunohistochemistry showing HBSAg phenotype. Two of the 63 cases given
      lamivudine + HBIG developed reinfection with serum HBSAg, HBeAb, HBcAb positive
      and liver biopsy immunohistochemistry showing HBSAg phenotype. The serum HBV DNA
      was positive in one of the two cases. Three cases given adefovir developed no
      reinfection with HBV. CONCLUSION: Orthotopic liver transplantation is an
      effective treatment for HBV infection; lamivudine + HBIG or adefovir + HBIG
      prevent hepatitis B virus reinfection.

PMID- 15561236
TI  - Incidence and risk factors of renal dysfunction after liver transplantation in
      Korea.
AB  - Renal dysfunction, one of the most common complications after liver
      transplantation, influences patient outcomes. Little is known, however, about it
      in Korea. The aims of this study were to determine the incidence and to identify
      the risk factors for renal dysfunction after liver transplantation. Sixty-two
      patients who survived over 6 months after transplantation were enrolled. Renal
      function was classified by creatinine clearance (Ccr, mL/min), which was
      estimated using the Cockcroft-Gault formula. Twenty-seven patients (44%) showed
      mild renal dysfunction (60 < or = Ccr < 90), and 27 patients (44%), moderate
      dysfunction (30 < or = Ccr < 60). The others were found to have normal function
      (Ccr > or = 90). None displayed severe dysfunction (Ccr < 30). Compared to a
      control group (Ccr > or = 60), the renal dysfunction group showed lower
      preoperative Ccr (91 +/- 28.6, 63 +/- 21.9, respectively, P < .01) and lower Ccr
      at 3 months after transplantation (72 +/- 17.1, 49 +/- 14.6, respectively, P <
      .05). Age, sex, immunosuppressive drug usage, serum tacrolimus levels, and the
      frequency of postoperative acute renal failure did not affect the postoperative
      renal dysfunction. Twenty-six patients received mycophenolate mofetil while
      reducing the dose of calcineurin inhibitors because of compromised renal
      function. With mycophenolate mofetil treatment, the renal function seemed to
      improve, although the difference was not statistically significant (P = .057).
      These data demonstrate that renal dysfunction is common after liver
      transplantation and that preoperative renal function is the important factor
      predicting postoperative renal dysfunction.

PMID- 15561237
TI  - Decreased proteinuria following liver transplantation in a patient with type C
      liver cirrhosis complicated with nephrotic syndrome: a case report.
AB  - Type C liver cirrhosis is often associated with a nephrotic syndrome secondary to
      membranoproliferative glomerulonephritis. Liver transplantation in such patients
      may sometimes worsen viremia, causing renal dysfunction upon the introduction of
      immunosuppressive drugs. We present a case of a patient whose proteinuria
      decreased after liver transplantation. The patient was a 49-year-old male who had
      been followed due to chronic hepatitis type C from 1984. From 1999 he was
      diagnosed as having nephrotic syndrome. We performed a living related liver
      transplant on August 21, 2001. An intraoperative renal biopsy revealed the
      histology to show membranoproliferative glomerulonephritis. The volume of
      proteinuria was 2 to 11 g/day before surgery. After surgery it varied from 6 to
      10 g/day, gradually decreasing to 1 to 2 g/day. One of the causes of reduced
      proteinuria may be alleviation of membranoproliferative glomerulonephritis by
      immunosuppression. But from the view that the recovery of the renal function
      followed the recovery of liver function, the major effect may have been
      alleviated hepatorenal syndrome.

PMID- 15561238
TI  - Renal impairment and diabetes mellitus after liver transplant.
AB  - INTRODUCTION: One of the major concerns in liver transplant patients who survive
      past 1 year posttransplant is the development of chronic diseases. AIM: We
      studied two important clinical conditions that can have a chronic course-renal
      impairment and diabetes mellitus-among long-term liver transplant survivors.
      METHODS: All adult patients transplanted and followed for at least 1 year were
      evaluated for clinical status, blood tests, and imaging studies. The occurrence
      and development of renal impairment, defined as a serum creatinine above 125
      micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were
      evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean
      age at transplant of 50 years had a mean follow-up duration of 45 months. The
      incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3
      years. This disorder was associated with pretransplant renal impairment and with
      a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6%
      with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment
      appears to be a potential long-term problem. Although this relates to
      pretransplant conditions, longer follow-up is required to examine whether
      posttransplant factors contribute to its progression.

PMID- 15561239
TI  - Acute renal failure after cadaveric related liver transplantation.
AB  - Acute renal failure (ARF) is a frequent medical complication after liver
      transplantation (LT). We analyzed cadaveric related liver transplant recipients
      who had developed ARF early in the postoperative course. Between January 1982 and
      August 2003, a total of 67 patients underwent cadaveric related LT. Their mean
      age was 28.64 years at LT. The 67 recipients had the following indications:
      biliary atresia (n = 17), Wilson's disease (n = 15), hepatitis B-related liver
      cirrhosis (n = 14), hepatitis C-related liver cirrhosis (n = 4), primary biliary
      cirrhosis (n = 4), hepatitis B-related liver cirrhosis with hepatoma (n = 3),
      hepatitis C-related liver cirrhosis with hepatoma (n = 2), Budd-Chiari syndrome
      (n = 2), neonatal hepatitis (n = 1), choledochus cyst (n = 1), autoimmune
      cirrhosis (n = 1), neuroendocrine tumor (n = 1), and hemangioendothelioma (n =
      1). Forty-nine patients received cyclosporine (CsA), azathioprine, and steroids
      and 18, a combination with tacrolimus (FK506). Eight (11.94%) patients developed
      ARF at a mean time of 17.25 days after LT. The mean peak serum creatinine was
      2.24 mg%. Four of these patients had a diagnosis of hepatitis B-related liver
      cirrhosis; two, hepatitis C-related liver cirrhosis; one, primary biliary
      cirrhosis; and one, hepatitis B-related liver cirrhosis with hepatoma. The ARF
      etiology was multifactorial for the majority of patients. Eight ARF patients had
      a history of liver cirrhosis, which may be a risk factor for intraoperative ARF.
      ARF treatment included fluid replacement, decreased or altered immunosuppressive
      agents, avoiding exposure to nephrotoxic drugs, and adjusting antibiotic dosages.
      The majority of patients returned to normal renal function at 1 to 3 weeks after
      the diagnosis of ARF. No patient required dialysis and/or experienced a
      mortality. We conclude that the incidence of ARF is relatively low and with good
      outcomes. ARF etiology was multifactorial for the majority of patients, but eight
      patients had a history of liver cirrhosis, which may be a risk factor for
      intraoperative ARF. We suggest that in the early postoperative period of LT cases
      diagnosis and treatment of ARF are important.

PMID- 15561240
TI  - Persistent thrombocytopenia in liver transplant patients.
AB  - INTRODUCTION: The occurrence of thrombocytopenia in the perioperative period
      after a liver transplant is not uncommon. However, there are few studies on
      persistent thrombocytopenia during the longer follow up period of patients after
      liver transplantation. We examined the prevalence of and contributing factors to
      persistent thrombocytopenia beyond 1 year post-liver transplantation. METHODS: We
      analyzed adult patients followed for at least 1 year posttransplant with full
      blood counts and abdominal scans, as well as clinical notes. RESULTS: The 35
      patients of mean age at transplant of 50 years and showed a mean follow-up of
      about 4 years showed a prevalence of persistent thrombocytopenia at 12 months of
      54% and at 3 years of 25%. Factors that were associated with persistent
      thrombocytopenia were pretransplant variceal bleeding, splenomegaly, and
      thrombocytopenia at 3 and 6 months posttransplant. After multivariate analysis
      only the latter represented independent factors for persistent thrombocytopenia
      at 1 and 3 years posttransplant, respectively. CONCLUSION: Persistent
      thrombocytopenia improved over time posttransplant; no bleeding problem was
      observed among the affected cases.

PMID- 15561241
TI  - Revealing the cause of cryptogenic cirrhosis by posttransplant liver biopsy.
AB  - INTRODUCTION: Because of the tendency for preexisting diseases to recur following
      liver transplantation, studying the course of patients who were transplanted for
      their cryptogenic cirrhosis may reveal features of the original cause. We
      examined the clinicopathological posttransplant progression of patients
      transplanted due to cryptogenic cirrhosis with emphasis on the detection of
      posttransplant steatosis and steatohepatitis. METHODS: The data on all patients
      transplanted for cryptogenic cirrhosis and their routine 1-year posttransplant
      liver biopsies were compared to a control group of a randomized sample of
      patients transplanted for other indications matched for length of follow-up. The
      posttransplant histological diagnosis was based on the latest available biopsy.
      RESULTS: Among 1710 patients, 39 present with cryptogenic etiology survived at
      least 1 year after transplantation. The control group consisted of 78 patients.
      The mean ages of the two groups were 50.7 and 49.3 years and the mean follow-up
      periods 6.2 and 5.7 years, both of which were similar. There was a significantly
      greater prevalence of posttransplant steatosis and steatohepatitis among the
      cryptogenic group (37.5 vs 16.7%, P = .048). The difference in patients with at
      least moderate steatosis was more pronounced (18.8 vs 3.3%, P = .035). Half of
      these cases progressed to fibrosis and cirrhosis after 48 months. CONCLUSIONS:
      This study found a greater incidence of allograft steatosis and steatohepatitis
      among patients transplanted for cryptogenic cirrhosis compared with a control
      group. A significant proportion of these patients developed a picture resembling
      nonalcoholic steatohepatitis, which progressed to fibrosis and cirrhosis.

PMID- 15561242
TI  - Early postoperative complications in recipients of living donor liver
      transplantation.
AB  - PURPOSE: Complications are common in the early postoperative period after living
      donor liver transplantation (LDLT). The aims of this analysis were to describe
      and identify risk factors for early postoperative complications. METHODS: Between
      June 1994 and June 2003, 140 consecutive LDLT patients were divided into 3
      groups: group I was small infants <9 kg (n = 30); group II, pediatric patients (n
      = 63); and group III, adult patients (n = 47). The complications within 3 months
      after operation were analyzed. RESULTS: The mortality rate was 1.4%. Surgical
      complications requiring relaparotomy occurred in 7.9% of patients. Intraoperative
      portal vein thrombosis requiring immediate thrombectomy, which occurred in 10
      patients, was significantly more frequent in the small infant group (23.1% vs
      3.2% vs 2.1%; P < .01). Acute hepatic artery thrombosis that occurred in 2
      patients was remedied successfully using operative rearterilization. Hepatic
      outflow obstruction requiring radiological interventions developed in 5 subjects.
      Medical complications included the following: pulmonary (14.3%), renal (19.3%),
      bacteremia (10.7%), cytomegalovirus infection (9.3%), and drain-related
      infections (20.7%). The incidence of hospital-acquired renal insufficiency was
      significantly higher in adult patients (3.3% vs 14.3% vs 36.2%; P < .01). There
      was no significant difference in the incidence of acute cellular rejection
      between members of the 3 groups (10.0% vs 17.5% vs 17%; P = .63). CONCLUSIONS:
      Sophisticated postoperative care with multiple disciplinary involvements may
      achieve a low early mortality rate in LDLT. Small infants weighing <9 kg may
      carry a greater risk of intraoperative portal vein thrombosis. Pulmonary
      complications and renal function impairments were the most troublesome in
      pediatric and adult recipients, respectively.

PMID- 15561243
TI  - Hepatic venous stenosis in partial liver graft transplantation detected by color
      Doppler ultrasound before and after radiological interventional management.
AB  - Hepatic outflow insufficiency remains one of the major complications causing
      postoperative graft failure especially among partial liver graft transplantations
      (PLT) including living donor liver transplantation (LDLT), reduced size liver
      transplantation (RLT), and split liver transplantation (SLT). These procedures
      are different from the whole liver graft transplantations (OLT), which include
      multiple vascular anastomoses. Color Doppler ultrasound (CDUS) was used to
      evaluate the hepatic venous outflow from grafts before and after radiological
      interventional management and to document treatment effects. From June 1994 to
      March 2003, our 136 cases of PLTs included 131 LDLTs, two RLTs, and three SLTs.
      Seven cases (six children and one adult) showed postoperative hepatic vein
      outflow obstruction and persistent massive ascites, as detected by color Doppler
      ultrasound (CDUS) and confirmed by interventional angiography. The CDUS showed a
      monophasic flat waveform with a relatively low hepatic vein average peak velocity
      (Va) in all cases (mean 11 cm/s). Successful interventional procedures included
      balloon dilatation in three cases and metallic stent replacement in four cases.
      CDUS was used with guidance during the procedure to confirm restoration of normal
      hepatic vein flow with a multiphasic waveform and an objective increase of
      average flow velocity (high to average 66 cm/s). Ascites disappeared dramatically
      after the procedure. In conclusion CDUS is the prime modality to diagnose and
      document a treatment response.

PMID- 15561244
TI  - Efficacy of double-filtration plasmapheretic cross-circulation with a high
      permeability membrane using canine harvested liver in porcine fulminant hepatic
      failure model.
AB  - INTRODUCTION: The use of bioartificial liver devices requires. A sufficient liver
      cell mass to provide adequate metabolic support, reduction of xenogeneic immune
      reactions, and avoidance of viral transmission. We have developed a
      plasmapheresis system using a semipermeable membrane combined with canine whole
      liver perfusion (PMCWLP). In this study, we investigated the efficacy of our
      system in a porcine fulminant hepatic failure (FHF) model. METHODS: The porcine
      FHF model was established by intraportal administration of alpha-amanitin (0.1
      mg/kg) and lipopolysaccharide (1 microg/kg). Nine hours after drug injection,
      xenogenic perfusion treatment was performed twice within 6 hours (n = 5). As the
      plasmapheresis device, we used a hollow-fiber module with cellulose diacetate
      porous fibers (pore size, 0.05 microm, surface area, 2 m2). The canine whole
      liver was perfused with modified Krebs solution, which is commonly used in many
      laboratories, containing albumin (2 g/dL) and glucose (300 mg/dL). Control pigs
      (n = 10), had the circuit not connected to the whole canine liver. RESULTS: The
      survival of FHF pigs was significantly increased by the treatment (58.9 +/- 21.8
      hour) compared with the controls (22.3 +/- 8.1 hour). Mean blood ammonia levels
      and intracranial pressure during treatment were significantly lower compared with
      control groups. CONCLUSION: Treatment of FHF pigs with the system significantly
      increased survival time, suggesting that this method may have applications as a
      clinical liver assist device.

PMID- 15561245
TI  - In vitro evaluation of cross-circulation system using semipermeable membrane
      combined with whole liver perfusion.
AB  - INTRODUCTION: Many types of isolated hepatocytes-based bioartificial liver have
      been developed. However, to maintain hepatocyte-specific functions for a long
      period is still a significant challenge. The possibilities of rejection or viral
      transmission still remain as untackled obstacles. We developed a cross
      circulation system, using a semipermeable membrane combined with whole liver
      perfusion. Detoxifying functions of the extracorporeal porcine liver and
      molecular movements across the membrane were evaluated in vitro. METHODS: The
      hollow-fiber module has a molecular cutoff of 100 kD. A spiked solution
      containing 500 mL low molecular dextran solution spiked with 12 mg ammonium
      chloride, 500 mg D-galactose, and 300 mg lidocaine, which mimicked a patient, was
      recirculated through the inner fiber space. The extracorporeal liver perfusion
      circuit consisted of an extra-fiber spaces. A reservoir containing 1000 mL
      healthy pig plasma, a membrane oxygenator, and a porcine whole liver. Both
      circuits circulated in the opposite direction for 6 hours. RESULT: In 6 hours,
      47.3% +/- 10.2% of ammonia, 89.5% +/- 1.7% of D-galactose, and 95.5% +/- 1.0% of
      lidocaine were eliminated from the circuits; 66.5 +/- 11.1 mg of urea were
      produced at the same time. Oxygen consumption was maintained between 0.248 and
      0.259 mL/100 g liver/min for 6 hours. Movement of IgM was completely blocked by
      the 100-kD membrane, whereas albumin was freely transferred from the reservoir to
      the intrafiber space. CONCLUSION: The perfusion experiments showed the
      possibility of using a whole liver with oxygenated plasma perfusion in a
      bioartificial liver system in vitro.

PMID- 15561246
TI  - Partial hepatectomy and subsequent radiation facilitates engraftment of mouse
      embryonic stem cells in the liver.
AB  - For liver-targeted regenerative medicine, embryonic stem (ES) cell-derived
      hepatocyte-like cells proffer great expectation. In vitro exposure to a
      combination of various growth factors, such as hepatocyte growth factor and
      fibroblast growth factor-4, as well as cytokines, leads to differentiation of ES
      cells into hepatocyte-like cells. We sought to determine the in vivo environment
      that allowed engraftment of ES cells transplanted to the liver. Thus, we examined
      the effect of partial hepatectomy (50%) (PHT) and subsequent radiation (RT) of
      the male Balb/c mouse host liver on ES cell engraftment. ES cells (5 x 10(6))
      derived from 129Sv mice were transplanted into the residual liver. The controls
      were ES cells transplanted into a normal liver. Bromo-deoxy-residine (BrdU)
      uptake was performed to evaluate the effect of hepatectomy and RT on hepatocyte
      regeneration. Mouse ES cells engrafted, forming teratomas in the normal liver
      without showing any mononuclear infiltration. A liver modified by PHT and RT
      facilitated engraftment of mouse ES cells compared with a normal liver. Hepatic
      RT significantly suppressed hepatocytic uptake of BrdU.

PMID- 15561247
TI  - Usefulness of artificial liver support for pretransplant patients with fulminant
      hepatic failure.
AB  - This study assessed the usefulness of artificial liver support (ALS) for
      pretransplant patients with fulminant hepatic failure (FHF). Five patients (age
      14 to 52 years, 3 men and 2 women) with FHF who were being prepared for living
      donor liver transplantation (LDLTx) were enrolled in this study. ALS included
      plasma exchange, using 40 to 50 units of fresh frozen plasma per session, and
      high-flow hemodiafiltration, using a high-performance polysulfone membrane.
      Variables such as circulatory and respiratory function, coma grade, and
      neurologic disorders were evaluated. Although systolic and diastolic blood
      pressures showed no statistical differences between pre-ALS and post-ALS, the
      difference in heart rates was statistically significant. After ALS initiation in
      the pre-LDLTx period, one of the three patients who needed mechanical ventilation
      was weaned from it. After LDLTx, all patients recovered neurologically; no
      neurologic disorder was observed. These results suggested that ALS could predict
      neurologic status after LDLTx. The difference in coma grades also achieved
      statistical significance. Our study indicates that short-term ALS is useful for
      improving circulatory and respiratory function prior to liver transplantation, as
      well as for predicting posttransplantation neurologic status. Although some
      patients recover by ALS alone, the survival rate of ALS-only patients is less
      than 50%. ALS prolongs intensive treatment, thus increasing both the risk of
      infection and the medical costs. Further investigation to determine a precise
      marker for liver regeneration will be needed to establish a consensus on the
      indications for long-term ALS. We conclude that ALS is useful to improve
      circulatory and respiratory functions among pretransplant patients, and to
      predict neurologic status after LDLTx.

PMID- 15561248
TI  - Changes in serum LECT 2 levels during the early period of liver regeneration
      after adult living related donor liver transplantation.
AB  - We investigated changes in serum leukocyte cell-derived chemotaxin2 (LECT2)
      levels between donors and recipients in the early period during liver
      regeneration following adult living related donor liver transplantation (LRDLT).
      Five recipients (three women, two men; 37.0 +/- 15.8 years old), all of whom had
      end-stage liver failure, underwent LRDLT from healthy five donors (two women,
      three men; 41.6 +/- 14.3 years old) between June 2000 and February 2001. FK506
      and methylprednisolone were used as immunosuppressants for recipients. Serum
      LECT2 levels decreased immediately after both the hepatectomy in all donors and
      the implantation of liver graft in all recipients. Donors showed a nadir at 3 to
      12 hours, increasing at 24 to 48 hours. The nadir in recipients occurred several
      hours after the donors. The serum LECT2 levels of donors were significantly
      higher than those of recipients on day 5 (9.5 +/- 5.9 ng/mL vs 3.1 +/- 2.2 ng/mL,
      P = .04) and on day 7 (9.3 +/- 3.8 ng/mL vs 3.5 +/- 1.1 ng/mL, P = .04). Serum
      GPT and GOT levels were inversely proportionate to the serum LECT2 levels. The
      present studies suggest that LECT2 participates in liver regeneration and injury
      following hepatectomy.

PMID- 15561249
TI  - Serum LECT2 level as a prognostic indicator in acute liver failure.
AB  - In the present study, we investigated the relationship between serum leukocyte
      cell-derived chemotaxin2 (LECT2) levels and liver function in patients with acute
      liver failure, and its use as a prognostic indicator. We studied six acute liver
      failure patients (two women, four men; 49.8 +/- 20.7 years old) admitted to our
      hospital in 2002. These patients had diagnoses of fulminant hepatitis due to
      acute liver failure (1) from congestive heart failure; (2) from portal venous
      gas, and (3) from postoperative disseminated intravascular coagulation (DIC). We
      measured serum LECT2, GOT, and GPT levels, the last two being inversely
      proportionate to the serum LECT2 levels. When the serum GPT levels peaked, the
      serum LECT2 levels were the lowest. When the liver function recovered, serum
      LECT2 levels increased. Three of four patients died due to liver failure, one to
      congestive heart failure. Maximum serum LECT2 levels among the expired group were
      significantly lower than those among the alive group (0.96 +/- 0.8 ng/mL vs 12.9
      +/- 4.3 ng/mL). Serum LECT2 levels may be a prognostic indicator of recovery from
      liver failure. The present study suggests that in clinical medicine LECT2
      participates in regeneration after injury of hepatocytes.

PMID- 15561250
TI  - Analysis of heart donation for cardiac transplantation at the National Taiwan
      University Hospital: fifteen-year cases review.
AB  - The demand for organ transplantation is disparate to the supply of organ donors.
      The organ shortage is a limitation for transplantation. This study analyzed the
      status of heart donors at the National Taiwan University Hospital (NTUH) from
      July 1987 through November 2001 using registry records. One hundred ninety-four
      total heart donors yielded about 25 donors per year in the late era (years of
      1995-2001). The majority of heart donors were men (78.4%) of O blood type (46.9%)
      with a mean age of 29.8 (SD = 11.9) years. Though head injury was the main source
      of heart donors (78.4%), cerebrovascular accident patients have increased (15%)
      since 1995. However, the number of donors from head injury decreased in the year
      of 1997, when Taiwan passed a law to force motorcycle drivers to wear safety
      helmets. The average interval from brain death to donation was 75.4 (SD = 71.2)
      hours. One hundred fifty-six (80.4%) of the 194 donor hearts came from outside
      hospitals. However, the majority of heart transplantations (166 cases, 85.6%)
      were done at the NTUH. Implementing a program for a smooth donation and organ
      procurement processes should provide better donor management in cardiac
      transplantation.

PMID- 15561251
TI  - Influence of UNOS status on chance of heart transplantation and posttransplant
      survival.
AB  - This study was designed to compare the chance of heart transplantation (HTx) and
      survival among patients in different UNOS statuses in Taiwan. METHODS AND
      RESULTS: From 1996 to 2002, among 203 patients on the heart transplant waiting
      list, 127 patients had undergone HTx up to December 2002 with 71 dead while
      waiting, and 5 still alive without transplantation. This study included those 198
      patients who had either undergone HTx or who died. At the time of registry, 40
      patients were at status IA, 57 at IB, and 101 at II. Nineteen (47.5%) of 40
      status IA patients underwent HTx with a mean waiting time of 92 +/- 116 days and
      median waiting time of 35 days. The 1-month survival was 84%, and 1-year survival
      was 58%. Seven (64.9%) of 57 status IB patients underwent HTx with a mean waiting
      time of 85 +/- 100 days and a median waiting time of 40 days. Both 1-month and 1
      year survivals were 92%. Seventy-one (70.3%) patients among 101 status II
      patients underwent HTx. Their mean waiting time was 134 +/- 135 days and median
      waiting time was 86 days. Their 1-month survival was 95%, and 1-year survival was
      85%. CONCLUSION: Although UNOS status IA patients had a shorter waiting time,
      their chance to undergo HTx was lower than those in either status IB or status
      II. The UNOS status IA heart-waiting patients showed lower posttransplant 1-month
      and 1-year survival rates.

PMID- 15561252
TI  - Heart transplantation using donors positive for hepatitis.
AB  - From May 1994 to September 2003, 177 hearts were procured for heart
      transplantation (HTx) from donors ranging in age from 1 year 2 months to 66 years
      5 months (mean = 30 years). All donors and recipients received serologic tests
      for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), and hepatitis C
      virus antibody (anti-HCV). Thirty-two donors were HBsAg-positive and another four
      were anti-HCV-positive. Two HBsAg-positive donors were transplanted to patients
      with no previous evidence of hepatitis. After HTx, one received hepatitis B
      immunoglobulin prophylaxis and no hepatitis was noted during a 5 years follow-up.
      The other seroconverted at 4 months after HTx, requiring lamivudine treatment.
      Another four HBsAg-positive donors were transplanted to HBsAg-positive
      recipients. All four recipients had hepatitis flare-ups requiring lamivudine
      treatment. The other 26 HBsAg-positive donors were transplanted to anti-HBs
      positive recipients. None suffered from hepatitis. Among the four patients
      receiving anti-HCV-positive hearts, seroconversion was noted in one recipient at
      26 months. This patient never had clinical hepatitis before he died of allograft
      rejection at 3 years after HTx. The other three recipients remain anti-HCV
      negative during follow-up of 80, 50, and 46 months. It was concluded the
      hepatitis B- or C-positive donors could be used as heart donors for status 1
      patients. Donors with positive HBsAg may be transplanted to anti-HBs-positive
      recipients with no HBV infection.

PMID- 15561253
TI  - Heart transplantation at Cheng Hsin General Hospital in Taiwan: 15-year
      experience.
AB  - Heart transplantation (HTx) in Taiwan, which started in 1987, now includes more
      than 500 cases. From July 1988 to September 2003, we performed 215 cases of
      orthotopic HTx in 164 male and 51 female recipients of mean age of 47.3 +/- 14.3
      years, (range 2.7 to 74.9 years). The leading etiologies were dilated
      cardiomyopathy (CMP), 68.5%; ischemic CMP, 20.2%; and valvular CMP, 4.2%. The
      actuarial survival rates at 1, 5, and 10 years are 88.3%, 77.1%, and 57.2%,
      respectively. We performed the first case of HTx in Asia after bridging for 14
      days with an indigenous total artificial heart (TAH; the Phoenix-7 model); we
      performed the first case of infant HTx without blood transfusion and also the
      first case of autotransplantation of heart for repair of a left ventricular
      rupture after a mitral valve replacement. These cases were all successful with
      the longest surviving HTx recipient in Asia. We have used the biatrial
      anastomosis technique in all cases. We discovered familial CMP due to
      mitochondrial defects in two pediatric cases. Because of the scarcity of donor
      hearts, we have used size-mismatched hearts as well as suboptimal and hepatitis
      positive donor hearts, all with satisfactory outcomes. Our experience has shown
      comparable results to Western programs, with efficacy and cost-effectiveness. We
      find the technique of biatrial anastomosis for orthotopic HTx to result in a low
      incidence of tricuspid regurgitation and conduction anomalies. The use of
      suboptimal and size-mismatched donor hearts is also promising.

PMID- 15561254
TI  - Heart transplantation in the patient under ventricular assist complicated with
      device-related infection.
AB  - Ventricular assist devices (VAD) have benefited patients with end-stage heart
      failure as a bridge to heart transplantation (HTx). We present our experience of
      HTx in the presence of device-related infection (DRI) including driveline exit
      site with pocket infections. From May 1996 to April 2003, mechanical circulatory
      support with the HeartMate VAD was performed in eight patients, and with the
      Thoratec VAD in seven patients. Although 151 patients underwent HTx during that
      period, only 8 of the 15 patients had suitable donors and underwent orthotopic
      HTx. Six of the eight patients developed DRI. Their ages ranged from 18 to 59
      years (mean = 36 +/- 14 years). The duration of VAD support ranged from 8 to 287
      days (mean = 125 +/- 117 days). The general condition and cardiac function
      improved gradually under VAD support. At the time of HTx, all six male patients
      were suffering from DRI. The causative microorganisms were Acinetobacter
      baumannii (n = 3) methicillin-resistant Staphylococcus aureus (n = 2), and
      Enterococcus faecium (n = 1). All patients underwent successful HTx, and were
      discharged in good condition. It is concluded that under the coverage of
      appropriate antibiotics, HTx can be successfully performed for the patients for
      VAD support with DRI. It is important to prevent the spread of infection during
      HTx. Adequate debridement and drainage of the infected materials prevents
      postoperative wound infections.

PMID- 15561255
TI  - Heart transplant coronary artery disease in Chinese recipients.
AB  - BACKGROUND: Transplant coronary artery disease is the principle limiting factor
      for long-term survival of heart transplantation (HTx) recipients. We reviewed our
      data to assess the incidence of this disorder among Chinese HTx recipients and to
      compare it with the results of Western studies. MATERIAL AND METHODS: From July
      1988 to May 2002, 182 patients received 184 orthotopic HTx. One hundred sixty
      three recipients survived for at least 1 year with available SPECT scans or
      coronary angiogram studies. The data set included donor characteristics,
      recipient characteristics, active cytomegalovirus (CMV) infection rate, rejection
      episodes, immunosuppressants, and human leukocyte antigen (HLA) mismatches.
      RESULTS: Surgical mortality in our program was 4.3% and the actuarial freedom
      from coronary artery disease at 1, 3, and 5 years was 99%, 95%, and 92%,
      respectively. Angiogram results were stratified into coronary artery disease (n =
      15) or absence of the disorder (n = 148) groups. Only older donor age showed
      statistical significance between the groups. Compared with the Western series,
      the present data show higher actuarial survival rates and freedom from coronary
      artery disease. There were statistically significant differences in regard to
      graft ischemia time, proportion of male recipients, ischemic heart disease,
      rejection episodes during the first year, and incidence of CMV infection.
      CONCLUSIONS: SPECT scan can detect coronary artery disease before there is
      significant stenosis of the coronary artery with acceptable survival rates.
      Chinese HTx recipients show a lower incidence of the disorder, lower rates of
      ischemia heart disease, lower proportion of male gender, lower incidence of CMV
      infection, fewer rejection episodes during the first year, and less ischemic time
      than Western recipients, which maybe the contributing factors to their better
      survival.

PMID- 15561256
TI  - Efficacy and safety of tacrolimus versus cyclosporine microemulsion in primary
      cardiac transplant recipients: 6-month results in Taiwan.
AB  - INTRODUCTION: This study compared the efficacy and safety of a tacrolimus (TAC)
      based with a cyclosporine (CsA)microemulsion-based immunosuppressive regimen in
      primary cardiac transplantation. METHODS: Heart recipients were randomly assigned
      to receive either TAC or CsA regimen after sequential induction with rabbit anti
      thymoglobulin. Endomyocardial biopsies were performed at weeks 1, 2, 3, and 4 and
      months 2, 3, and 6. RESULTS: Among 21 adult patients (TAC, 11; CsA, 10) in this
      study, patient survival rates were 100% in both groups at the end of 6 months.
      One patient (9%) in the TAC group experienced acute rejection (ISHLT > or = 1B)
      versus 6 patients (60%) in the CsA group (P = .02). The effects on hematology,
      biochemistry, cytomegalovirus infection, and hemodynamics were similar in both
      groups except for better lipid profiles in the TAC group. There were no
      significant differences in severe adverse events. CONCLUSION: The TAC-based
      regimen had a lower risk of acute rejection compared with CsA in heart transplant
      recipients. The safety profiles were similar in both groups. Therefore, TAC is an
      alternative to CsA as a primary maintenance immunosuppressant in heart
      transplantation.

PMID- 15561257
TI  - Therapeutic drug monitoring of tacrolimus in cardiac transplant recipients: a
      comparison with cyclosporine neoral.
AB  - This study compares the pharmacokinetics of tacrolimus (TAC) and cyclosporine
      Neoral (CsA) in cardiac transplant recipients. METHODS: Twenty-six de novo
      cardiac recipients were prospectively and randomly assigned to receive oral TAC-
      or CsA-based regimens after 5 to 6 days of rabbit antithymocyte globulin
      induction. Blood samples were collected at 0 (before the dose) and 0.5, 1, 2, 3,
      4, 6, 8, 10, as well as 12 hours after drug administration. The pharmacokinetics
      of the first dose (PK-1) and at steady state (PK-S, 1 month after
      transplantation) were analyzed. RESULTS: Comparing the AUC per milligram dose,
      there was no significant difference between PK-1 and PK-S among TAC (46.0 +/-
      24.3 ng x h/mg x mL versus 69.0 +/- 43.9 ng x h/mg x mL, P = .15 by paired t
      test), but a significant difference in CsA (25.2 +/- 11.4 ng x h/mg x mL versus
      45.4 +/- 12.9 ng x h/mg x mL, P = .0005 by paired t-test). This means better TAC
      absorption in the early post-heart transplant period. Using a single-point blood
      level to predict AUC, TAC showed a significantly higher correlation than CsA at
      all corresponding sampling times. Besides, C12 in both PK-1 and PK-S of TAC
      displayed good correlations to the AUC (r2 = .895, P = .00 in PK-1 and r2 = .81,
      P = .00 in PK-S). The TAC trough level was accurate enough to predict the AUC.
      CONCLUSION: The pharmacokinetic profile of TAC is more reliable than that of CsA
      in the early post-heart transplant period. A high correlation of trough blood
      levels with AUC omits the requirement for a multiple sampling strategy to more
      accurately measure AUC as is needed with CsA.

PMID- 15561258
TI  - Therapeutic drug monitoring of tacrolimus in early stage after heart
      transplantation.
AB  - INTRODUCTION: Little is known about the pharmacokinetic (PK) profiles of
      tacrolimus (Tac) within the first week after heart transplantation (HT) in
      adults. Our objective was to investigate the PK profiles of Tac in early after
      HT. METHODS: Twenty-three adult HT patients received Tac as primary
      immunosuppression. Tac was administered orally at a starting dosage of 0.10
      mg/kg/d. The Tac dosages were adjusted to a target range of 10 to 20 ng/mL during
      the first 1 month after HT. The PK profiles were analyzed immediately after the
      first dose (PK1; n = 14), at day 3 (PK2; n = 10), and at day 7 (PK3; n = 8) to
      assess the relationships between PK parameters and acute rejection rates.
      RESULTS: The correlation between Tac trough levels and Tac-AUCs were r = .95 PK1;
      r = .82, PK2; and r = .88, PK3. When AUC(0-12h) was controlled in the range from
      150 to 300 ng x h/mL (10 to 20 ng/mL trough levels), 17 of 18 patients (94.4%)
      did not show evidence of significant rejection (72.2% grade 0, 16.7% 1A, and 5.5%
      grade 1B). One patient displayed a grade 2 biopsy score (5.5%). Mean AUC(0-12h)
      values of Tac were significantly lower among patients who experienced acute
      rejection than those who remained rejection-free (89 vs 217 ng x h/mL, P = .023).
      CONCLUSION: The initial trough levels are good indicators of systemic exposure.
      To reduce the risk of rejection and renal toxicity, the trough levels should be
      controlled in range from 10 to 20 ng/mL in early stage after HT.

PMID- 15561259
TI  - A limited sampling strategy for the estimation of 12-hour cyclosporine neoral
      area under the curve in Chinese cardiac transplant recipients.
AB  - INTRODUCTION: This study determined the accuracy of a limited sampling strategy
      to predict the 12-hour cyclosporine neoral (CsA) area-under-the-curve (AUC) to
      provide a practical method for more accurate therapeutic drug monitoring (TDM) of
      CsA in Chinese heart transplant recipients. METHODS: Blood samples were collected
      at 0 (before the dose), and 0.5, 1, 2, 3, 4, 6, 8, 10, as well as 12 hours after
      CsA oral administration in 13 de novo heart recipients receiving oral CsA bid
      after rabbit antithymoglobulin sequential immuno-induction. Pharmacokinetics were
      analyzed for the first dose (PK-1) and the steady state dose (PK-2, 1 month after
      transplantation). The limited sampling strategies included single-point, 2-point,
      and 3-point prediction of AUC using multiple linear regression analyses. RESULTS:
      Comparing the AUC/mg dose, PK-1 was much lower than PK-2 (25.2 +/- 11.4 ng x h/mg
      x mL vs 45.4 +/- 12.9 ng x h/mg x mL; P = .0005 using paired t test). The
      correlations of each single-point blood level of PK-1 with the AUC were lower
      than those of the corresponding sampling time in PK-2. In the PK-2 study, C4 had
      the best correlation (r2 = 0.732; P = .00) as a single-point to predict AUC, but
      the 2-point C2 + C12 had a higher correlation (r2 = 0.937; P = .00). Among the 3
      point combinations, C2 + C4 + C12 showen the best prediction (r2 = 0.982; P =
      .00) of the AUC in PK-2. CONCLUSION: The bioavailability of CsA was lower in PK-1
      than in PK-2. At steady state, we recommend C2 + C12 to predict AUC because it is
      accurate and not labor-intensive.

PMID- 15561260
TI  - Cyclosporine C2 monitoring is superior to C0 in predicting acute cellular
      rejection in heart transplant recipients in Taiwan.
AB  - The cyclosporine (CsA) blood concentration at 2 hours postdose (C2) has been
      shown to be better than trough level (C0) to predict acute cellular rejection
      (ACR) in solid organ transplantations. We tried to assess the superiority of C2
      monitoring to C0 in heart transplantation (HTx). Prospective data were collected
      from the HTx recipients from November 1991 to April 2003. The 100 patients
      surviving longer than 3 months after HTx, provided 237 sample sets, with ACR
      graded by endomyocardial biopsy (EMB) and concurrent C0 and C2 levels. ACR was
      defined as International Society of Heart and Lung Transplantation (ISHLT) grade
      lb or higher. Nonparametric methods, logistic regression model, and receiver
      operating characteristic (ROC) analysis were used. There was no significant
      demographic heterogeneity between ACR and non-ACR groups. C2 was significantly
      lower in ACR than non-ACR groups (P = .0192) whereas C0 showed no significant
      difference. In the logistic regression model, C2 was a significant predictor
      against ACR (P = .026, odds ratio = 0.76 per 100 ng/mL), but C0 was not. ROC
      analysis showed that C2 of 600 ng/mL might provide the optimal cut-off point,
      with a sensitivity of 51.23% and a specificity of 71.43%, but C0 did not show
      this association. In conclusion, C2 monitoring is superior to C0 for predicting
      ACR in HTx. ACR should be suspected when the C2 value is below 600 ng/mL.

PMID- 15561261
TI  - Various clinical presentations of tuberculosis in heart transplant recipients.
AB  - The purpose of this study was to clarify the various clinical presentations,
      incidence, and complications associated with tuberculosis (TB), as well as
      patient survival in heart transplantation (HTx) recipients. A retrospective
      review of 177 case records of HTx recipients from May 1989 to April 2003 were
      evaluated for their clinical course, diagnostic procedures, treatment, and
      survival. TB was diagnosed by culture. TB was proven in five (2.8%) patients.
      There were three pulmonary lesions and two extrapulmonary lesions. TB was
      diagnosed at 3.5 to 85 months after HTx. Pulmonary lesions were detected by
      cultures of sputum, bronchoalveolar lavage, or pleural effusion. For
      extrapulmonay lesions, one subject had neck lymphadenopathy shown by biopsy and
      culture to be TB; another suffered from swelling of the finger joints which upon
      culture of the aspirate proved to be TB. Treatment consisted of isoniazid (INH),
      rifampin (RIF), ethambutol, pyrazinamide, streptomycin (STR), ciprofloxacin
      (Ciproxin), and levofloxacin (Cravit). During the use of RIF, the daily dosage of
      cyclosporine (CsA) or tacrolimus was increased to maintain appropriate levels.
      Because of severe hepatotoxicity and interference with CsA, RIF was withdrawn and
      STR given in the last three patients. In addition, ciprofloxacin was given in the
      patient with miliary TB. Levofloxacin was given to the other two patients. All
      patients survived the TB infection under treatment with at least three drugs.
      There were five clinical presentations of TB in our HTx recipients. Because of
      the high incidence of hepatitis and severe drug interaction with CsA or
      tacrolimus on RIF treatment, avoiding the use of RIF but treatment with at least
      three drugs is recommended.

PMID- 15561262
TI  - A precious experience of lobar transplantation in a teenager with end-stage
      chronic hypersensitivity pneumonia: case report.
AB  - Pulmonary fibrosis inevitably develops in patients with chronic hypersensitivity
      pneumonia (CHP). Lobar transplantation may be a viable option for pediatric and
      small adult patients with end-stage CHP and life-threatening respiratory
      decompensation. We describe a 16-year-old girl experiencing end-stage pigeon
      breeder's hypersensitivity pneumonia with right heart failure, who received left
      allograft lobar transplantation and had an uneventful convalescent course for 1
      year after transplantation. Histopathologically the excised native lung revealed
      diffuse infiltration of lung parenchyma by CD3+ and CD8+ cells with an absence of
      CD4+ cells, whereas T-lymphocyte subsets analysis revealed no abnormalities in
      the blood. This finding is consistent with the contribution of a local type IV
      immune reaction to the pathogenesis. In addition, the observation of specific
      cellular distribution of bronchus-associated lymphoid tissue suggests that
      chronic antigenic stimulation and /or inflammation in CHP may cause bronchus
      associated lymphoid tissue development, which is likely to play an important role
      in the mucosal immune response of this disease.

PMID- 15561263
TI  - Comparison of canine single and sequential bilateral lung transplant model for
      lung preservation study.
AB  - The purpose of this study was to compare canine sequential bilateral lung
      transplantation (SBLT) with left single lung transplant (LSLT) models. After 24
      hours of lung preservation with low potassium/dextran glucose (LPDG) solution,
      seven SBLT procedures were performed using mongrel dogs. The comparative group
      including nine cases of LSLT. After completion of each transplant, the dogs were
      maintained on a ventilator for 3 hours. Thereafter serial hemodynamics were
      evaluated with recipients with chest X-ray, computed tomography, and lung
      perfusion scan checked at 2 hours after transplantation. Pathological evaluations
      were also performed. Five of seven SBLT successfully completed the whole
      assessment, all LSLT survived. In SBLT, pulmonary arterial pressure and pulmonary
      vascular resistance were significantly elevated, but recovered 3 hours after
      reperfusion. The ultrastructural aspects of alveolae and pulmonary artery
      endothelium showed a reversible mild injury 24 hours after lung preservation and
      reperfusion. The present study suggests that the canine SBLT model using LPDG
      solution provides an excellent preservation effect and is more physiological as
      the dog is completely dependent on the function of the transplanted lung.

PMID- 15561264
TI  - Complete replacement of tracheal epithelia by the host promotes spontaneous
      acceptance of orthotopic tracheal allografts in rats.
AB  - BACKGROUND: Tracheal immunogenicity has been controversial. Although replacement
      of allotracheal epithelia by the host epithelia has been reported in rat
      orthotopic tracheal grafting, the immunological effect of epithelial replacement
      is still uncertain. METHODS: We performed orthotopic tracheal grafting of nine
      cartilage rings in the following groups: 1, Lewis --> Lewis (n = 30); 2, ACI -->
      DA (n = 25); 3, Lewis --> F344 (n = 23); 4-A, DA --> Lewis (n = 41); 4-B, DA -->
      Lewis with tacrolimus therapy (1 mg/kg/d for 10 days) starting from the day of
      the operation (n = 31); 4-C, retransplantation of DA allografts to secondary
      naive Lewis rats 10 or 15 days after primary grafting (n = 11); 4-D, DA --> Lewis
      with tacrolimus therapy starting from postoperative day 10 (n = 6). Survival
      times and histopathology were assessed. Epithelial replacement was evaluated by
      immunohistochemistry. RESULTS: All rats survived in groups 1, 2, and 3. Even in
      the fully histoincompatible group 4-A, survival ratio on day 120 was 15%.
      Epithelial replacement was in progress on day 10 in this group. However, all
      tacrolimus-treated rats died by day 54 and epithelial replacement did not occur
      on days 30 and 50 in group 4-B. In group 4-C, retransplantation after complete
      epithelial replacement increased the long-surviving rats. In group 4-D, all rats
      receiving tacrolimus therapy after complete epithelial replacement survived over
      120 days. CONCLUSIONS: These results suggest that complete replacement of
      tracheal epithelia by the host promotes spontaneous acceptance of orthotopic
      tracheal allografts in rats.

PMID- 15561265
TI  - Relationship between immunological rejection and matrix GLA protein in
      cryopreserved vascular allografts.
AB  - INTRODUCTION: Cryopreserved tissue allografts used for cardiovascular diseases
      become calcified as a late complication after transplantation, probably caused by
      immunological rejection. Recent attention has been focused on the inhibitory
      effect of matrix Gla protein (MGP) on ectopic vascular calcification, but the
      behavior of MGP in cryopreserved allografts is uncertain. In this study we
      examined the relationship between immunological rejection and MGP in
      cryopreserved rat aortic grafts after transplantation. METHODS: Cryopreserved rat
      aortae were isografted or allografted intraperitoneally. Fresh isografts were
      also tested. The grafts were retrieved 9 days after transplantation and the
      intragraft MGP mRNA was measured by a real-time quantitative PCR method. The
      effect of daily administration of FK506 on MGP mRNA levels in cryopreserved
      isografts and allografts after transplantation was also evaluated. RESULTS: There
      was no significant difference in intragraft MGP mRNA levels between fresh and
      cryopreserved isografts 9 days after transplantation. MGP expression levels in
      cryopreserved allografts were significantly lower as compared to those in
      cryopreserved isografts (P < .01). Daily administration of FK506 enhanced
      intragraft MGP mRNA (ninefold) in cryopreserved allografts (P < .01), but not in
      cryopreserved isografts. CONCLUSIONS: Immunological rejection is likely to
      inhibit MGP expression in cryopreserved vascular allografts, resulting in late
      onset calcification.

PMID- 15561266
TI  - CD8 T cell of donor splenocyte mixed with bone marrow cells is more effective
      than CD4 T cell for induction of donor-specific tolerance in sublethally
      irradiated mice.
AB  - BACKGROUND: We previously demonstrated that even a low dose of bone marrow cells
      (BMCs) established donor-specific tolerance if mixed with splenocytes (SPLCs). In
      this study, T-cell subsets CD4 (CD4SP) and CD8 (CD8SP) of donor SPLCs were
      investigated for their contribution to the enhancement of BMC engraftment leading
      to donor-specific tolerance in sublethally irradiated mice. METHODS: Sublethally
      irradiated C57BL/6 recipient mice were intravenously injected BMCs mixing with
      CD4SP or CD8SP harvested from BALB/c donor mice. The degree of chimerism in the
      peripheral blood lymphocytes (PBLs) and in the SPLCs was analyzed using FACS,
      mixed lymphocyte reaction, and skin graft transplantation 3 months after
      injection. RESULTS: Recipients injected with 3 x 10(6) donor BMCs admixed with 10
      x 10(6) donor CD8SP established chimerism. However, recipients injected with the
      same dose of BMCs admixed with 5 x 10(6) CD4SP, 10 x 10(6) CD4SP, and 5 x 10(6)
      CD8SP did not established chimerism. CD8SP contained 44% of Ly6A/E (Stem Cell
      Antigen-1 (Sca-1))-positive cells based on FACS analysis, whereas only 6% of
      CD4SP were positive for Ly6A/E. MLR supernates of donor SPLCs chimeric mice using
      admixture with CD8SP dominated by Th2 cytokines. In contrast, mixting with MLR
      supernates from failed chimera showed dominant Th1 cytokines. CONCLUSIONS: CD8SP
      seems to make a major contribution to enhance BMC engraftment and induce donor
      specific tolerance. Ly6A/E (Sca-1)-positive cells need to be further investigated
      for their contribution to the establishment of chimerism.

PMID- 15561267
TI  - Ability of donor splenocytes with costimulation blockade to induce mixed
      hematopoietic chimerism and transplantation tolerance.
AB  - We reported stable mixed chimerism and specific tolerance to a fully allogeneic
      graft after a minimally myelosuppressive regimen including costimulation blockade
      (CB), donor bone marrow cells (BMC), and busulfan (Bu), a chemotherapeutic
      conditioning agent that makes niches for engraftment of BMC. For clinical
      application, the strategy may have the limitation of the number of donor BMC when
      a deceased donor offers transplants to multiple recipients. Herein, we examined
      whether donor splenocytes can serve as an alternative source to induce mixed
      chimerism and tolerance. When a C57BL/6 (H-2b) recipient was treated with CB
      (CTLA4-Ig and anti-CD154 mAb, on days 0, 2, 4, 6) and donor BALB/c (H-2d) BMC (2
      x 10(7) cells on day 0) in the absence of Bu, survival of BALB/c skin graft was
      remarkably prolonged but not indefinite (median survival time [MST]: 138 days).
      The recipients never showed durable chimerism. When the recipient was treated
      with CB and donor splenocytes ([DST] 2 x 10(7) cells on day 0), survival was not
      indefinite either (MST: 114 days). When the dose of DST was increased to 2 x
      10(8) cells, survival was further prolonged; two of six recipients had indefinite
      survival (MST: 132 days). Moreover, one recipient showed a low level of
      chimerism. When treated with CB, donor DST (2 x 10(7) cells on day 0) and Bu (20
      mg/kg, day -1), six of seven recipients showed a stable, high level of chimerism
      and enjoyed tolerance of skin allografts. DST combined with CB and Bu may be an
      alternative source of hematopoietic stem cells to induce mixed chimerism and
      transplantation tolerance in our model.

PMID- 15561268
TI  - Changes in expression of T-cell activation-related molecules and cytokines during
      tolerance induction in an allogeneic skin transplantation murine model.
AB  - Bone marrow transplantation after treatment with busulfan and costimulatory
      blockade with monoclonal antibodies (mAb) cytotoxic T lymphocyte antigen 4
      (CTLA4)-Ig and anti-CD154 mAb or two-signal blockade using anti-CD45RB and anti
      CD154 mAb are nonmyeloablative treatment regimens for allogeneic transplantation.
      There may be differences in the mechanisms of donor cell engraftment and reactive
      cell deletion by which these regimens induce donor-specific tolerance. Therefore,
      this study was performed to investigate changes in T cells and cytokines during
      tolerance induction toward allogeneic skin grafts. BALB/c and C57BL/6 mice were
      used as donors and recipients, respectively. Skin and bone marrow
      transplantations were performed and busulfan was administered. Three groups were
      treated with mAb as follows: group 1, anti-CD154 mAb; group 2, anti-CD154 plus
      anti-CD45RB mAb; and group 3, anti-CD154 mAb plus CTLA4-Ig. The proportions of
      CD4+ or CD8+ T cells and the expression of CD45RB isoforms on splenocytes were
      measured using flow cytometry and the production of cytokines by CD4+ T cells
      using enzyme-linked immunosorbent assay. Group 2 showed a significant reduction
      in the proportions of CD8+ T cells and CD45RB high isoforms compared with groups
      1 and 3. The levels of interleukin (IL)-2 and IL-4 in group 2 were lower and
      higher than those of groups 1 and 3, respectively. In conclusion, the combined
      use of anti-CD154 and anti-CD45RB mAb decreases the CD8+ T-cell population and
      the expression of CD45RB, resulting in a Th2 cytokine profile, which may be a
      characteristic mechanism leading to donor cell engraftment and reactive cell
      deletion for donor-specific tolerance.

PMID- 15561269
TI  - Prolongation of skin allograft survival by combined feeding of donor spleen cells
      and cyclosporine in mice.
AB  - BACKGROUND: Oral immune tolerance is a method for inducing donor-specific
      immunotolerance and prolonging graft survival. OBJECTIVES: We studied the effect
      of feeding donor spleen cells in combination with cyclosporine (CsA) on skin
      allograft survival in mice. METHODS: Tail skins from BALB/c (H-2d) female mice
      were transplanted onto C57BL/6 (H-2b) female mice. The animals were divided into
      four groups, each with eight mice: group I, untreated controls; group II, treated
      with spleen cells; group III, treated with CsA; and group IV, treated with spleen
      cells and CsA. All grafts were inspected daily. Rejection was diagnosed when the
      graft loss was >80% to 90%. The immune responses of C57BL/6 toward donor mice
      were examined by delayed-type hypersensitivity (DTH). RESULTS: Survival times of
      allogeneic skin grafts in groups I, II, III, and IV were 9.9 +/- 0.6, 13.1 +/-
      0.6, 14.7 +/- 0.9, and 20.0 +/- 0.7 days, respectively. When compared with group
      I, the survival times of groups II, III, and IV were prolonged significantly (P <
      .01). The survival time for group IV was prolonged significantly compared with
      groups II and III (P < .01). The DTH responses of group IV were decreased
      significantly in contrast to groups II and III (P < .01). CONCLUSIONS: Feeding
      donor spleen cells prolonged the survival of skin allografts in mice; combination
      with CsA led to further prolongation of skin allograft survival.

PMID- 15561270
TI  - Fibronectin suppresses apoptosis and protects mice from endotoxic shock.
AB  - Multiple-organ failure related to septicemia is a common cause of early mortality
      after liver transplantation. Endotoxemia following living donor hepatectomy may
      be a cause of postoperative death. Plasma fibronectin (Fn) exerts a broad range
      of biological effects on cellular adhesion, motility, differentiation, apoptosis,
      hemostasis, wound healing, reticuloendothelial system function, and ischemic
      injury. We studied the therapeutic effect of plasma Fn in mice after an
      intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (GalN).
      Female Balb/c mice received simultaneous intraperitoneal injection of LPS (50
      microg/kg) and GalN (400 mg/kg). Thirty minutes prior to GalN/LPS administration,
      plasma Fn or bovine serum albumin was given intravenously. A single
      administration of plasma Fn (500 mg/kg) protected in dose-dependent fashion
      against lethal shock after GalN/LPS challenge. Plasma Fn significantly reduced
      the serum tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 levels
      and significantly increased the serum interleukin-10 levels after GalN/LPS
      administration. Furthermore, plasma Fn significantly inhibited liver necrosis at
      9 hours after GalN/LPS injection. The fraction of apoptotic-positive cells in
      these plasma Fn-treated mice was significantly lower than in the control group.
      These results support the protective treatment of endotoxin-induced liver injury
      by plasma Fn.

PMID- 15561271
TI  - Allogeneic T-cell apoptosis induced by interleukin-10-modified dendritic cells: a
      mechanism of prolongation of intestine allograft survival?
AB  - BACKGROUND: Genetic modification of donor dendritic cells (DC) is a potential
      therapy for allograft rejection. We hypothesized that in vitro interleukin-10
      (IL)-10-transfected DC (DC-IL-10) may induce allogeneic T-cell apoptosis,
      resulting in prolonged allograft survival rat small intestine. METHODS: Myeloid
      DC from Wistar-Furth rats (RT-1u) were propagated with rrGM-CSFand rrIL-4,then
      genetically modified to express the hIL-10 gene. Secretion of IL-10 was
      quantitated by enzyme-linked immunosorbent assay (ELISA). Allogeneic T cells from
      Lewis (LEW; RT-1(l)) at proliferative responses were determined by MTT assay in
      primary mixed leukocyte reactions. We then used a combination of DNA agarose gel
      electrophoresis, acridine orange staining, and Annexin V/propridium iodide assays
      to examine apoptosis of allogeneic T cells exposed to DC-IL-10. Then 5 x 10(6)
      donor-derived DC-IL-10 or untransduced DC were injected intravenously 7 days
      before small intestine transplantation (WF-->LEW). RESULTS: DC-IL-10 showed
      pronounced impairment of T-cell allostimulatory activity. Apoptotic T cells were
      detected in the DC-IL-10 group. Flow cytometry counting at 72 hours showed 45.1%
      apoptotic T cells in response to DC-IL-10, whereas the untransduced group did not
      undergo significant apoptosis (P < .01). DC-IL-10 pretreated recipients showed
      moderate prolongation of allograft survival compared with controls (20.7 +/- 6.0
      days vs 7.5 +/- 2.2 days, P < .01). CONCLUSIONS: DC-IL-10 induced allogeneic T
      cell hyporesponsiveness in vitro, possibly due to apoptosis. DC-IL-10 pretreated
      recipients displayed prolonged intestinal allograft survival rates.

PMID- 15561272
TI  - Antioxidant supplementation may improve renal transplant function: a preliminary
      report.
AB  - Dysfunction of the renal graft may not only be due to rejection but also other
      causes such as ischemia and reperfusion injury and calcineurin inhibitor
      nephrotoxicity. Antioxidant free radical scavengers may decrease oxidative stress
      and lipid peroxidation. Previous animal studies suggest that vitamins C (ascorbic
      acid) and E (alpha-tocopherol) are both strong antioxidants, that decrease
      oxidative stress caused by ischemia-reperfusion injury and calcineurin inhibitor
      nephrotoxicity. But there have been only limited reports about clinical efficacy.
      We report five cases supplemented with vitamin C (500 mg per day), vitamin E (500
      mg per day), or both. After a 1- to 3-month prescription, the serum creatinine
      level decreased more than 20% from the original value. Interestingly, one patient
      had this experience: he ceased vitamin E for 1 month due to noncompliance. The
      serum creatinine level increased more than 50%. When he took vitamin E again, his
      serum creatinine level declined and returned to the previous level. From our
      limited experience, antioxidant supplementation with vitamin C or E may improve
      renal transplant function, especially in grafts donated from marginal donors.

PMID- 15561273
TI  - Expression of lectin-like oxidized low-density lipoprotein receptor-1 in
      allografted hearts.
AB  - The pathogenesis of posttransplant coronary artery disease, which is thought to
      be a major form of chronic rejection after cardiac transplantation, is not fully
      understood. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) on
      endothelial cells induces reduction of NO release and up-regulation of adhesion
      molecules, thereby contributing to the development of vascular atherosclerosis.
      Herein, we investigated the expression of LOX-1 mRNA in murine allografted hearts
      that develop diffuse coronary obstruction. Allogeneic (C57BL/6 to BALB/c) and
      syngeneic (C57BL/6 to C57BL/6) heterotopic cardiac transplants were removed the
      10th posttransplant day. LOX-1 mRNA expression was measured by RT-PCR. The
      heartbeat of the allografts gradually weakened and was almost stopped on day 10,
      whereas syngeneic hearts continued to pulsate throughout the experiment.
      Histologically, allografts showed fibrous luminal narrowing of the coronary
      arteries with severe mononuclear cell infiltration. In contrast, the vascular
      architecture of syngeneic grafts was almost normal. Marked increase in LOX-1 mRNA
      expression was observed only in allografts. The results indicate that alloimmune
      responses induce up-regulation of LOX-1 mRNA in transplanted hearts. Increased
      LOX-1 may be involved in the progression of obstructive vascular changes.

PMID- 15561274
TI  - Time course of gene expression after the injection of adenoviral vectors
      containing CTLA4IG gene.
AB  - INTRODUCTION: In vivo gene transfection using a recombinant adenoviral vector
      leads to diminished gene expression in a time-dependent manner that disappears
      within 4 weeks. CTLA4Ig blocks CD28-mediated costimulatory signal, and inhibits
      immune responses. We investigated the duration of transgene expression after
      administration of adenoviral vector containing CTLA4Ig gene (AdCTLA4Ig). METHODS:
      We injected 1 x 10(9) plaque forming units (pfu) of AdCTLA4Ig into rats (n = 7)
      via the tail vein. Thereafter, the blood samples were collected for assay of
      serum CTLA4Ig levels using enzyme-linked immunosorbent assay. RESULTS: The
      CTLA4Ig level reached the maximum (range, 65-86 microg/mL; average, 75 microg/mL)
      on days 3 to 5 after injection. Detectable levels of CTLA4Ig were observed up to
      49 days. When we injected AdCTLA4Ig in combination with FTY720 administration,
      the maximum levels were higher and the detectable levels persisted longer.
      CONCLUSIONS: Because directly injected adenoviral transgene expression had been
      reported to disappear between 21 to 30 days, we conclude that AdCTLA4Ig inhibits
      the immune response and prolongs the transgene (CTLA4Ig gene) expression. Some
      additional immunosuppressants, like FTY720, may be useful to enhance AdCTLA4Ig
      effects.

PMID- 15561275
TI  - Syenergistic effect of 15-deoxyspergualin with costimulation blockade on
      alloimmune response.
AB  - INTRODUCTION: A virally induced alloreactive memory seems to represent a potent
      barrier to tolerance induction but the combination of 15-deoxyspergualin (DSG),
      an inhibitor of NFkB translocation, with costimulation blockade (CB)-based
      chimerism as an induction regimen can overcome a preformed anti-donor memory
      response. In this study, we investigate the ability of DSG with CB to inhibit a
      naive alloimmune responses. METHODS: A BALB/c (H-2d) skin or heart was
      transplanted into a C57BL/6 (H-2b) recipient treated with anti-CD154 mAb (MR1;
      500 mcg/d on days 0, 2, 4, 6) alone, DSG (5 mg/kg/d, days 0 to 7) alone, or both
      agents. Proliferation of alloreactive T cells after each treatment was also
      examined using a graft-versus-host disease (GvHD) model using the fluorescent dye
      CFSE. RESULTS: Treatment with DSG alone induced prolonged survival of the cardiac
      allografts (median survival time [MST]: 97.5 days). MR1 alone induced indefinite
      survival of cardiac allografts, although at 150 days after transplantation, the
      histology showed changes characteristic of chronic rejection, including
      interstitial fibrosis, infiltration of mononuclear cells, and intimal hyperplasia
      in coronary vessels. Combined treatment with DSG and MR1 induced donor-specific
      unresponsiveness in all recipients, graft histology showed only minimal
      infiltration. Treatment with DSG and MR1 also significantly prolonged the
      survival of skin allografts (MST: 31 days) compared with that of DSG or MR1 alone
      (MST: 17 and 14 days, respectively). In the GvHD model assessed with CFSE, the
      combined treatment was the more effective to suppress proliferation of
      alloreactive T cells while DSG alone inhibited proliferation more than MR1 alone.
      CONCLUSION: DSG potentiates anti-CD154 therapy to suppress the alloimmune
      response.

PMID- 15561276
TI  - Prolonged heart allograft survival resulted from donor-specific T-cell
      sequestering and removal by selective splenectomy in mice.
AB  - INTRODUCTION: Selective splenectomy when donor antigen-specific activated T cells
      are sequestered in the recipient spleen may prolong allograft survival because of
      removal of all of these T cells. OBJECTIVES: We investigated the effect on
      cardiac allograft survival in mice by means of removal of activated specific T
      cells by splenectomy. METHODS: Donor (Balb/c) spleen cells were injected into
      primed allogeneic recipients (C57BL/6). Selective recipient splenectomy and donor
      type cervical heart grafting in Balb/c to C57BL/6 from mice were examined at 0,
      24, 48, and 72 hours after donor spleen cell infusion. RESULTS: Control C57BL/6
      mice rejected Balb/c heart grafts at 6.86 +/- 0.19 days. Delayed heart grafting
      plus splenectomy at 24 or 48 hours after donor-type spleen cell infusion
      significantly prolonged heart allograft survival (24 hours: 15.86 +/- 3.44 days,
      P < .001; 48 hours: 21.71 +/- 5.22 days, P < .001, respectively). However, 72
      hour delayed heart grafting plus splenectomy failed to prevent acute rejection
      (72 hours: 9.57 +/- 2.51 days, P > .01). Immunohistochemistry showed, at 24 to 48
      hours after donor antigen infusion, the recipient spleens characterized by an
      obvious increase in CD4+ CD8+ T cells in periateriolar lymphoid sheaths, marginal
      zones, and red pulp compared with the 72-hour group. CONCLUSIONS: Transient
      accumulation of donor-specific activated T cells in the spleen of recipients
      provide an opportunity to remove all of these T cells by a surgical procedure. As
      the largest immune organ the spleen is the main place where T cells are activated
      and regenerated. At 24 or 48 hours when donor-specific T cells were sequestered
      in the spleen after donor antigen stimulation, selective recipient splenectomy
      was able to remove the T cells and prolong was allograft survival. Refinement of
      this protocol may eventually warrant clinical application.

PMID- 15561277
TI  - Rat model of orthotopic gastric transplantation.
AB  - INTRODUCTION: We tried to find a better surgical procedure of reconstruction
      after total gastrectomy. Seventy rats were operated to establish a model of
      orthotopic gastric transplantations which may also be important for abdominal
      multivisceral transplantation. OBJECTIVE: To establish a rat model of orthotopic
      gastric transplantation. METHODS: In the donor operation; after the spleen was
      resected and the proper hepatic artery ligated, the stomach was infused with cold
      (0 degrees C to 4 degrees C) sodium lactate Ringer's solution via the aorta. The
      stomach was resected with its peripheral blood vessels-the celiac trunk, the left
      gastric artery, the splenic artery, the common hepatic artery, the gastroepiploic
      artery, and the portal vein. In the recipient operation; after the stomach and
      the spleen were resected, the donor stomach was implanted. An end-to-side
      anastomosis was performed for the portal veins. After the end-to-end anastomosis
      between the donor celiac trunk and the recipient left gastric artery, the blood
      flow was opened. Then the anastomoses of the duodenum, and donor cardia to the
      recipient esophagus were performed in end-to-end style. RESULTS: Thirty five
      operations were performed, in which the success rate in the last 20 cases was 80%
      (16/20). The average operative time was 2.35 hours. The longest survival time was
      over 3 months. CONCLUSION: A rat model of orthotopic gastric transplantation was
      successfully established and provides a method to study abdominal multivisceral
      transplantation. It also provides a new way for reconstruction after the total
      gastrectomy.

PMID- 15561278
TI  - A study of the relationship between the graft length, site, and rejection in
      small bowel transplantation.

PMID- 15561279
TI  - Effects of FTY720 on rat lymphoid organs.
AB  - INTRODUCTION: In this study, we examined the in vivo effect of FTY720 on rat
      thymus and spleen. MATERIALS AND METHODS: Inbred male Lewis (RT-I(l)) rats, 5
      weeks-old, received FTY720 (0.1, 1, or 10 mg/kg) by intramuscular injection into
      1 of 4 limbs daily for 7 days. The rats were humanely killed at 1, 3, 5, or 7
      days after starting administration of FTY720. The thymus and spleen were obtained
      for hematoxylin and eosin (HE) as well as immunoperoxidase staining using the
      antibodies OX8 (CD8), W3/25 (CD4), and OX6 (major histocompatibility complex
      class II). RESULTS: HE staining revealed marked atrophy in the cortical region of
      the thymus among rats administered FTY720 at the dose of 10 mg/kg. The atrophy
      extended to the whole cortex. On day 7 of administration of FTY 720 (10 mg/kg),
      the medulla of the thymus showed relative expansion due to cells accumulation.
      Also, the spleens of FTY720-treated rats revealed an obvious reduction in the T
      cell-dependent areas around the central artery. In conclusion, the
      immunosuppressive effect of FTY720 may be due to an inhibitory effect on T-cell
      emigration from the thymus to the periphery.

PMID- 15561280
TI  - A new method to immortalize primary cultured rat hepatocytes.
AB  - BACKGROUND: In conventional methods of establishing hepatocyte cell lines, the
      immortalizing gene alone is introduced into hepatocytes. We designed a new method
      in which not only the immortalizing gene, the simian virus-40 large T-antigen (SV
      40 Tag) gene, but also a drug-resistant gene, under the control of an albumin
      enhancer/promoter, were introduced into hepatocytes to efficiently obtain
      immortalized hepatocyte cell lines. METHODS: The plasmid pAPUR contains the
      puromycin-resistant gene under the control of an albumin enhancer/promoter, and
      the pSVTag contains the early region of SV-40 enhancer/promoter and the SV-40 Tag
      gene. Both pAPUR and pSVTag were transferred into isolated rat hepatocytes by
      electroporation. After these cells were cultured on a collagen-coated dish for 24
      hours, puromycin selection was started. Expression levels of albumin, alpha
      fetoprotein (AFP), SV-40 Tag, and cytokeratin 19 (CK 19) in the transformed cells
      were evaluated by western analysis, immunocytochemical staining, and RT PCR.
      RESULTS: Approximately 3 weeks after transfection, five or six colonies appeared
      on the dish. Twenty strains were obtained by cloning these cells. All strains
      that were similar to immature hepatocytes expressed albumin and SV-40 Tag,
      although CK 19 was not detected. AFP expression was detected in 33% of these
      strains. CONCLUSIONS: All clones cotransfected by pAPUR and pSVTag expressed
      albumin. Our new method may be useful to establish hepatocyte cell lines.

PMID- 15561281
TI  - The viability and function of cryopreserved hepatocyte spheroids with different
      cryopreservation solutions.
AB  - We sought to evaluate the viability and function of cryopreserved hepatocyte
      spheroids using different cryopreservation solutions in order to elucidate the
      efficiency of cryopreservation. Hepatocytes isolated from a Sprague-Dawley rat
      were formed into spheroids by 24 hours of rotational culture. The spheroids were
      cryopreserved using a programmed linear freezer in a liquid nitrogen tank for 24
      hours in four different cryopreservation solutions: UW solution (UW), William E
      media (WE), fetal bovine serum (FBS), and a mixture (MIX). After thawing, they
      were cultured for 4 days. With each hepatocyte spheroid, the viability using the
      MTT assay and hepatocyte-specific functions, such as ammonia clearance, urea
      nitrogen synthesis, and albumin secretion, were analyzed. The viabilities of
      cryopreserved hepatocyte spheroids were 64.8% +/- 10.2% (UW), 33.2% +/- 9.7%
      (WE), 69.3% +/- 8.7% (FBS), and 48.4% +/- 15.5% (MIX). Ammonia clearance of
      spheroids cyropreserved in UW solution was 0.93 +/- 0.13 mmol/L per well per day,
      which was not significantly different from freshly cultured spheroids. From the
      aspect of urea nitrogen synthesis, spheroids cryopreserved with UW, FBS, and MIX
      solution were not significantly different from freshly cultured spheroids. The
      amount of albumin secretion by the UW cryopreserved spheroids was significantly
      greater than that of other cryopreserved spheroids. Cryopreserved hepatocyte
      spheroids in UW solution were not significantly different from freshly cultured
      spheroids with respect to viability and function. UW solution was superior to
      other cryopreservation solutions for viability and functions.

PMID- 15561282
TI  - Sustained release of vascular endothelial growth factor from calcium-induced
      alginate hydrogels reinforced by heparin and chitosan.
AB  - A possible alternative for immunosuppression is a microencapsulation technique
      using hydrogels, which have been utilized for cell immobilization and drug
      delivery systems. Angiogenesis is crucial for delivery of the metabolic products
      to the host tissues as well as to supply oxygen and nutrients to cells. The local
      delivery of angiogenic growth factors, such as VEGF and basic FGF, has been
      recently studied to enhance angiogenesis on peripheral tissue of graft. In this
      study, we evaluated sustained VEGF release with a model using hydrogels coated
      with chitosan and heparin in vitro. We fabricated calcium alginate gels and
      chitosan-coated calcium alginate gels. Heparinized chitosan-coated calcium
      induced alginate hydrogel beads were prepared by soaking chitosan-coated calcium
      alginate gels in heparin solution. We compared the stability and VEGF release
      manner between three kinds of hydrogels. To compare the stability, 5 mL of each
      hydrogel was incubated with 20 mL PBS under the rotational culture. Compression
      forces were measured using a rheometer. The amount of VEGF released from the gels
      was measured by ELISA. The heparin-coated chitosan alginate hydrogels showed the
      highest surface stability among the three hydrogels. VEGF from the heparinized
      gel was released in sustained manner up to 10 days in vitro. Chitosan-coated
      alginate gels released 90% of loaded VEGF within 5 days. These results suggest
      that local delivery of VEGF using a heparinized hydrogel may provide a long-term
      supply of angiogenic growth factor that might induce new vessel formation in
      vivo.

PMID- 15561283
TI  - A new source of hepatocytes for transplantation.
AB  - INTRODUCTION: The most effective treatment for acute or chronic liver failure is
      orthotopic liver transplantation. Worldwide there is a shortage of organs for
      transplantation. This shortage has called for research into new treatments for
      management of patients with liver failure. One such treatment is hepatocyte
      transplantation. During liver resections considerable amounts of normal liver are
      unavoidably resected. We aim to harvest these hepatocytes and to filter the tumor
      cells from them to provide a source for transplantation. MATERIALS AND METHODS:
      After liver resection, the largest vessel at the resected liver edge was
      identified and cannulated. Seglen's two-stage technique of perfusing the liver
      with EDTA and collagenase was performed to harvest the hepatocytes. Ep-CAM Ags
      are consistently present on the surface of epithelial cells and in particular in
      colorectal cancer cells. Therefore, MOC31 antibodies (selective Abs for Ep-CAM)
      attached to magnetic beads were used to target the tumor cells. These tumor cells
      are selectively removed using a magnet. CEA staining was then used to ensure the
      hepatocyte collection was tumor cell free. Five million hepatocytes were rosetted
      with one million HT29 CRC cells to assess the immunomagnetic filtration
      technique. RESULTS: The hepatocyte harvesting resulted in 864,000 viable
      hepatocytes to be harvested per gram of liver. Histochemical staining using CEA
      demonstrated 75% of the HT29 cells in the hepatocyte collection were removed
      after one use of magnetic beads. CONCLUSION: We have demonstrated the successful
      initial stages of harvesting tumor-free hepatocytes from liver resected for
      malignancy.

PMID- 15561284
TI  - Extracellular matrix component cotransplantation prolongs survival of
      heterotopically transplanted human hepatocytes in mice.

PMID- 15561285
TI  - A study of HLA-G1 protection of porcine endothelial cells against human NK cell
      cytotoxicity.
AB  - Human natural killer (NK) cells, which can directly lyse porcine endothelial
      cells, play an important role in xenotransplantation. HLA-G is a nonclassical
      major histocompatibility complex (MHC) class I molecules that has been implicated
      in protecting susceptible target cells from lysis by NK cells. The objective was
      to study the effect of protecting porcine endothelial cells transfected with HLA
      G1 from human NK cell lysis. METHODS: The recombinant expression vector pcDNA3
      HLA-G1 was transfected into primary cultured porcine aortic endothelial cells
      (PAECs) by lipofection. Surface expression of HLA-G1 in transected PAECs was
      confirmed by an immunofluoresence technique. Peripheral blood mononuclear cells
      (PBMC) and NK cell line (NK92) were used as NK effects cells with pcDNA3-HLA-G1
      transfected PAECs as targets in a MTT method using pcDNA3 transfection as a
      negative control. RESULTS: Expression of HLA-G1 on PAECs conferred significant
      protection against NK-mediated lysis. The rate of NK92 cytotoxicity was reduced
      to 41.5% +/- 14.0% from 75.3% +/- 10.5% in the control group (P < .01). Similarly
      the rate of the PBMC cytotoxicity among different donors (n = 7) was reduced to
      45.4% +/- 12.1% in contrast to 74.6% +/- 11.2% in the control group (P < .05).
      CONCLUSIONS: HLA-G1 molecules can directly protect xenogeneic PAECs against
      attack by human NK cells. These results indicate that the expression of HLA-G1 on
      the porcine cell surface may provide a new approach to overcome NK-mediated
      immunity to xenografts.

PMID- 15561286
TI  - The novel molecule porcine OSR1 up-regulated expression on porcine endothelial
      cell by human peripheral blood mononuclear cell activation.
AB  - INTRODUCTION: Clinical xenotransplantation is being considered to overcome the
      shortage of human organ donors. In our previous studies, using human-anti-porcine
      xenogeneic mixed mononuclear cell-endothelial cell cultures with the suppression
      subtractive hybridization method, we obtained a subtracted cDNA library that
      included about 300 clones corresponding to up-regulated genes. One porcine
      sequence showed 81% identity with the human oxidative-stress responsive 1 (OSR1)
      molecule. The objective of this study was to confirm the gene up-regulation and
      obtain the full-length sequences. METHODS: The full-length gene was cloned
      through the technique of rapid amplification of cDNA ends (RACE). The other
      methods included bioinformatics analysis and RT-PCR. RESULTS: RT-PCR confirmed
      that the gene was up-regulated upon the interactions of human peripheral blood
      mononuclear cells (PBMCs) and porcine endothelial cells. By SMART RACE technique,
      we obtained the full-length cDNA of porcine OSR1. The gene is 4333 bp. The open
      read frame of 1590 bp encodes 529 amino acid residues. GenBank accession number
      is AY271356. The gene shows 92.8% nucleotide identity and 95.5% amino acid
      identity with human OSR1. CONCLUSION: We obtained the full-length cDNA of porcine
      OSR1. It was up-regulated on porcine endothelial cells following activation by
      human PBMCs. We succeeded in constructing a pcDNA-pOSR1 recombinant eukaryotic
      cell expression vector, the function of which is the subject as our ongoing work.

PMID- 15561287
TI  - Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac
      xenotransplantation.
AB  - BACKGROUND: CTLA4 immunoglobulin (CTLA4 Ig), which binds with high affinity to B7
      1 and B7-2, interrupts T-cell activation by inhibiting the costimulatory signal.
      CTLA4Ig has been used to achieve antigen-specific tolerance induction in cardiac
      allografts. On the other hand, we have shown that short-term administration of
      deoxyspergualin (DSG) and daily cyclosporine (CsA) induces long-term survival of
      cardiac xenotransplants. We hypothesized that the combination therapy of DSG and
      adenovirus-mediated CTLA4IgG might induce long-term, survival or tolerance in
      cardiac xenotransplantation. OBJECTIVES: Syrian hamster hearts were transplanted
      heterotopically into Lewis rats. We compared the survival time and
      immunopathology of the following five groups: (1) no treatment; (2) DSG (5 mg/kg
      per day intramuscularly [IM], days -1 to +7) alone; (3) CsA (15 mg/kg per day IM,
      day 0 to rejection) plus DSG; (4) AdexLacZ (LacZ-adenovirus 1 x 10(9) (PFU
      intravenously [IV], day -7) plus DSG; and (5) AdexCTLA4IgG (CTLA4IgG-adenovirus 1
      x 10(9) PFU IV, day -7) plus DSG. RESULTS: The survival times were: (1) no
      treatment, 3.7 days; (2) DSG alone, 12.4 days; (3) CyA plus DSG, >100 days; (4)
      AdexLacZ plus DSG, 11.0 days; and (5) AdexCTLA4IgG plus DSG, 23.6 days.
      Adenovirus-mediated CTLA4IgG therapy with DSG prolonged survival time
      significantly compared with DSG alone or AdexLacZ plus DSG, but CTLA4IgG therapy
      was not as effective as CsA. Immunopathology showed the deposition of C3 and IgM
      on the endothelium in the AdexCTLA4IgG plus DSG group. CONCLUSIONS: We showed
      that the effectiveness of adenovirus-mediated CTLA4IgG gene therapy in cardiac
      xenotransplantation in less than that of CsA. Combination therapy with inhibition
      of the B7/CD28 constimulatory signal and DSG administration might not be
      sufficient for long-term survival or tolerance in cardiac xenotransplantation.

PMID- 15561288
TI  - Pathogenesis and pathology of delayed xenograft rejection in pig-to-rhesus monkey
      cardiac transplantation.
AB  - It has been recognized that delayed xenograft rejection (DXR) is the major
      barrier to the acceptance of xenotransplantation after overcoming hyperacute
      rejection. OBJECTIVES: This study sought to investigate the pathogenesis and
      pathology of delayed xenograft rejection following pig-to-rhesus monkey heart
      xenotransplantation. METHODS: Heterotopic xenogeneic heart transplants in the
      abdominal cavity were performed using piglet donors to four monkey recipients.
      Complete complement depletion was achieved in the recipients with repetitive
      doses of high-activity cobra venom factor (Y-CVF). The recipients were
      immunosuppressed with a combination of cyclosporine, cyclophosphamide, and
      steroids. Sera were analyzed for C3 and C4 levels and complement activity and
      anti-pig endothelial xenoantibody. The grafts were examined histopathologically
      and immunohistochemically for C3, C4;C5b-9, IgM, IgG, tumor necrosis factor-alpha
      (TNF-alpha), intercellular adhesion molecule-1(ICAM-1), CD57(NK cells), CD68
      (macrophages), CD4, and CD8. RESULTS: Xenografts survived 8, 10, 13, and 13 days
      respectively, all developing DXR. Venous thrombosis was the outstanding feature
      within DXR xenografts, complicated by interstitial edema, local hemorrhage,
      myocardial necrosis, and mild to moderate cellular infiltration. The serum C3
      levels and complement activity decreased to almost 0 from the day of
      transplantation due to treatment with Y-CVF. The C4 level began to decrease 2 to
      4 days before the cardiac xenografts lost their function. Anti-pig endothelial
      xenoantibody also decreased after transplantation, slightly increasing during
      DXR. All rejected xenografts showed C3, C4, C5b-9, IgG, and IgM deposits to
      various degrees. Large numbers of macrophages (50% of total leukocytes)
      infiltrated the entire xenograft with a few natural killer cells (8% to 10%), as
      well as some CD4+ T cells (15%) and CD8+ T cells (25%). Upregulation of ICAM-1 on
      graft endothelial cells and TNF-alpha in the interstitium were also demonstrated
      in the rejected heart. CONCLUSION: Both humoral and cell-mediated immunologic
      reactions may play important roles in the pathogenesis of DXR. Besides C3, C4,
      C5b-9, IgM, and IgG destroying the xenograft, NK cells, macrophages, and CD4+ and
      CD8+ T cells may further aggravate the development of DXR.

PMID- 15561289
TI  - The study of new SLA classical molecules in inbreeding Chinese Wuzhishan pig.
AB  - The pig may be used as an alternative organ donor source in the future. The
      Wuzhishan miniature pig (WZSP) is a Chinese inbred mini pig with the highest
      inbreeding coefficient and has been used in many biologic experiments. We studied
      the classical MHC molecules of WZSP to confirm its pure gene background and to
      provide information for xenotransplantation. METHODS: The classical class I (P1
      and P14) and class II (DQA, DQB, DRA, and DRB) molecules were studied using RT
      PCR. The products were cloned into a pGEM-T vector, respectively, sequenced and
      compared with related data for homology analysis. RESULTS: WZSP is highly
      homologous (>90%) with NIH miniature swine for class I and class II molecules
      amino acids in alpha-3 domain responsible for the binding of human T-cell CD8
      were largely conserved; only two critical residues were altered. The critical
      residues of class I molecules recognized by human natural killer (NK) cells were
      completely different from humans. Furthermore, new class II molecules were
      homologous (>70%) with the Chinese south population in amino acids. The amino
      acids for binding to human CD4 were identical in DRB and showed only two
      differences in DRA. CONCLUSIONS: WZSP bears new alleles in porcine MHC-relevant
      loci. We might alter residues of class I molecules to avoid killing by human NK
      cells. The striking similarities of DRB would make WZSP less likely in compatible
      in xeno-rejection. We can also alter the two residues of the DRA sequence to make
      WZSP a better model for xenotransplant research in China.

PMID- 15561290
TI  - Screening and analysis of porcine endogenous retrovirus in Chinese Banna minipig
      inbred line.
AB  - Pigs have been the most likely animal as the source of cells, tissues, and organs
      for xenotransplantation. But the use of pigs in xenotransplantation is associated
      with the risk of porcine endogenous retrovirus (PERV) transmission. Previous
      studies have identified that the proviruses are integrated into the genome of
      normal pigs and that virus particles released from the porcine cells can infect
      human cells in vitro. As a unique inbred pig, Banna minipig inbred (BMI) has a
      huge potential value for xenotransplantation and medical research. It has been
      the focal experimental animal for pig-to-human xenotransplantation in China, due
      to its clear genetic background and tiny individual differences. To evaluate
      whether the potential risk of PERV exists in inbred pigs, a series of screening
      experiments were performed herein. The results of PCR with primers specific for
      gag, pol, and env showed that proviruses existed in the genome of BMI, and the
      PERV subtypes were PERV-A and PERV-B. PERV mRNA was expressed functionally in
      BMI. Positive results of an RT assay identified that PERV in BMI had potential
      infectivity, but the concentration of PERV reverse transcriptase in BMI was
      almost 20 times lower than that of HIV. These results suggested that gag, pol and
      env genes of PERV were not lost during inbreeding, which created favorable
      conditions to produce viral particles that could possibly infect human cells in
      xenotransplantation.

PMID- 15561291
TI  - Study of renal function matching between Banna Minipig Inbred line and human.
AB  - Pigs have been thought to be ideal candidates for xenotransplant donors. However
      besides the immunological barrier, physiological and pharmacokinetic
      comparabilities of kidney function between donor animals and humans are important
      factors for successful xenotransplantation. As a unique large inbred animal,
      Banna Minipig Inbred (BMI) has been reported to be a potential large animal
      suitable for xenotransplantation. However, its physical and pharmacokinetic
      compatibilities with humans have not been documented. The purpose of this
      investigation was to measure renal routine function, glomerular filtration rate
      (GFR), renal blood flow (ERPF), and drug metabolism to evaluate comparability to
      humans. The results suggested that the renal function of BMI was similar to that
      of humans to eliminate nonprotein nitrogenous end products of metabolism.
      Pharmacokinetics of p-aminohippurate (PAH) and inulin--the most widely used
      methods to assess ERPF and GFR--showed that BMI showed lower values than humans
      for GFR, but similar function to humans in ERPF. The pharmacokinetics of
      cefazolin; a widely used model drug to study kidney drug metabolizing capacity,
      showed greater overall renal drug elimination of BMI than of humans. These
      results suggested that BMI did show comparable data to human renal function.

PMID- 15561292
TI  - Activation of human coagulation system by liver-derived clotting factors of Banna
      minipig inbred line.
AB  - The liver synthesizes most of the coagulation factors that play a major role in
      arresting hemorrhage. Matching hepatic coagulation factors is an important
      premise in successful xenotransplantation. As a unique inbred pig, the Banna
      minipig inbred (BMI) animals have a huge potential value for pig-to-human
      xenotransplantation, due to its clear genetic background and tiny interindividual
      differences. Whether the coagulation factors synthesized by porcine liver can
      trigger human clotting pathways has not been reported. This study focused on the
      activities of BMI coagulant factors synthesized exclusively by the liver to
      activate human clotting pathways. In these experiments we prepared coagulant
      factors II, V, VII, X, and XII synthesized exclusively by liver from BMI and
      humans. The factors were used in common correction tests, added to the
      corresponding factor-deficient human plasma to determine prothrombin times or
      activated partial thromboplastin time, thereby calculating BMI and human
      coagulant factor activities. BMI clotting factors XII, VII, and X triggered human
      intrinsic, extrinsic, and common pathways, respectively. BMI clotting factors II,
      V, VII, X, and XII activities were 3.2-, 3.7-, 4.7-, 2.9-, and 4.5-fold as potent
      as those from humans.

PMID- 15561293
TI  - Study of hepatic function matching between Banna minipig inbred and humans.
AB  - As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig
      to-human xenotransplantation due to its clear genetic background and minor
      interindividual differences. Previous studies of BMI have focused on
      immunological barriers between BMI and humans. However, a comparison of liver
      function between donor animals and humans is an essential premise for successful
      xenotransplantation. In this study, we investigated routine hepatic functions,
      protein electrophoresis, and drug metabolism to compare capacity of liver
      synthesis, metabolism, and drainage between BMI and humans. The results showed no
      significant differences in the concentrations of albumin and globulin synthesized
      in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI
      were higher than those in humans, and levels of total bilirubin and direct
      reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance
      of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16
      times greater than that by humans, with a mean residual time of antipyrine in
      BMI, one-tenth of that in human. These findings suggested that BMI livers are
      similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in
      bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have
      stronger functions compared with those of humans. No incompatibility was
      identified in hepatic function between BMI and humans.

PMID- 15561294
TI  - Phylogenetic analysis of porcine endogenous retrovirus variation in three Chinese
      pigs.
AB  - PCR amplification was performed on genomic DNA extracted from peripheral blood
      lymphocytes of three species of Chinese pigs (Banna minipig inbreed [BMI], Wu-Zhi
      Shan pig [WZSP], and Nei jiang pig [NJP]), using primers corresponding to the
      highly conserved regions of polymerase (pol) gene. Extracted PCR products were
      then cloned in a pGEM-T vector. Phylogenetic analysis of the nucleotide sequences
      of BMI-PERV, NJJP-PERV, and WZSP-PERV revealed them to be a novel category of
      PERV. In comparison to other type C retrovirus and lentivirus, their amino acid
      sequenced show about 30% to 57.7% identities. Our previous research demonstrated
      that PERV in the three pigs was highly expressed. It appears likely that
      functional loci encoding these novel PERV sequences exist, but this remains to be
      established. The novel sequences described in this report will allow such
      investigations to be actively pursued.

PMID- 15561295
TI  - Evolving transplant options for multiple myeloma: autologous and nonmyeloablative
      allogenic.
AB  - High-dose chemotherapy supported by a single autologous hemopoietic stem cell
      transplant is considered by many to be the "standard of care" for suitable newly
      diagnosed patients with multiple myeloma. The majority of myeloma patients,
      however, still die from their disease. Approaches to improve response and overall
      survival rates include tandem autologous transplants, nonmyeloablative allogenic
      transplants, and posttransplant maintenance and immunotherapy strategies. Support
      for tandem autologous transplantation comes from single-center studies as well as
      the recently reported large IMF94 trial that demonstrated a statistically
      significant increase in both event-free and overall survival for the double
      transplant arm. A number of subsequent, but as yet less mature, studies have been
      presented recently. Although there is some support for the conclusions of the
      IMF94 trial, the exact place of this therapy is yet to be resolved. Reduced
      intensity allogeneic transplantation has been proposed as an alternative to
      conventional allogenic transplantation as a means of reducing the high transplant
      related morbidity and mortality of the latter procedure while still retaining the
      advantages of the allogeneic graft. Preliminary reports suggest a reduction of
      acute transplant-related complications, although graft-versus-host disease
      remains a significant issue. Finally, a variety of posttransplant strategies and
      novel therapeutic agents are in active development.

PMID- 15561296
TI  - Stem cell research and transplantation: science leading ethics.
AB  - One of the most exciting developments in the biological sciences in the past
      decade has been the discovery and characterization of human embryonic stem cells
      (ESCs). The interest to transplanters is the potential applications of stem cells
      in regenerative medicine (RM), which may involve tissue engineering, genetic
      engineering, and other techniques to repair, replace, or regenerate failing
      tissues and organs. There is little controversy surrounding human adult stem
      cells. However, human ESCs are surrounded by a number of ethical controversies,
      the extent of which is partly dependent on their source. Those derived from
      currently existing embryonic stem cell lines are less controversial than those
      derived from "excess" embryos from in vitro fertilization (IVF) clinics, while
      ESCs derived from IVF embryos specifically created for the purpose are not
      acceptable to many people arguing from religious and other moral perspectives.
      Somatic cell nuclear transfer, or therapeutic cloning, must be distinguished from
      reproductive cloning. It holds the most promise for regenerative medicine. ESCs
      can also be derived from gonadal ridges of aborted fetuses. The transplant
      community must strive to uphold societal values in its effort to find remedies
      for their ailing patients and address the perennial problem of organ shortage.
      Transplanters also have a responsibility to engage the public in their efforts to
      gain public understanding and support, and policy makers must take into account
      public opinion. Only in this way can we realize the great potential of stem cell
      research for organ transplantation.

PMID- 15561297
TI  - Xenogeneic embryonic stem cell-derived cardiomyocyte transplantation.
AB  - PURPOSE: The purpose of this study was to investigate the survival of xenogeneic
      embryonic stem cell (ES cell)-derived cardiomyocytes transplanted into the normal
      myocardium. MATERIAL AND METHODS: Undifferentiated mouse ES cells carrying the
      enhanced green fluorescent protein (EGFP) were cultured in hanging drops and then
      plated onto dishes. These cells were identified as cardiomyocytes by the
      expression of cardiac-specific genes, recording of action potential, and
      immunostaining with anti-sarcomeric myosin antibody. Donor cells were injected
      into the normal myocardium, with cyclosporine administered daily. One week after
      the transplantation, we investigated donor cell survival by examining EGFP
      expression, hematoxylin and eosin staining, and immunostaining with anti
      sarcomeric myosin antibody. RESULTS: In vitro donor cells derived from ES cells
      expressed myosin light chain-2v and alpha-myosin heavy chain genes, had action
      potentials of a ventricular myocyte type, and were stained by anti-sarcomeric
      myosin antibody. In vivo 1 week after transplantation, EGFP-expressed cells were
      detected in the cell transplanted area. No lymphocytic infiltration was observed
      around these cells. CONCLUSIONS: ES cell-derived cardiomyocytes survived in the
      normal myocardium after the transplantation, even in a discordant xenogeneic
      transplantation model. These results indicate that cell transplantation using
      cardiomyocytes derived from ES cells, even if xenogeneic represents an attractive
      strategy for treating heart disease.

PMID- 15561298
TI  - Hematopoietic stem cell transplantation for beta-thalassemia major: experience in
      south of Iran.
AB  - INTRODUCTION: Allogeneic stem cell transplantation as a curative treatment for
      thalassemia major was established in Shiraz in 1993. In this article we describe
      our results of 10 years experience with allogeneic bone marrow transplantation
      for thalassemia major. METHODS: From June 1993 to January 2003, 112 cases of beta
      thalassemia major underwent allogeneic marrow transplantation from HLA-identical
      or one antigen-mismatched related donors. Conditioning chemotherapy included
      busulfan (14 to 15 mg/kg), cyclophosphamide (200 mg/kg), and antithymocyte
      globulin (ATG; 40 mg/kg). Prophylaxis for graft-versus-host disease consisted of
      cyclosporine, prednisolone, and methotrexate. RESULTS: One hundred twelve
      patients with a diagnosis of beta-thalassemia major underwent allogeneic marrow
      transplantation during this period. The mean age of the patients was 9.5 years
      with the range of 2 to 20 years. The distribution of cases according to the
      Lucarelli classification were: 27 cases class I, 38 cases class II, and 47 cases
      class III. Eighty-seven of 112 patients (77.6%) with diagnosis of beta
      thalassemia major are living with full engraftment at a median follow-up of 6
      years (range 2 to 119 months). CONCLUSION: Allogeneic bone marrow transplantation
      has changed the outcome of disease dramatically. According to our results stem
      cell transplantation is the treatment of choice for class I and II (Lucarelli
      risk groups). Also, we recommend transplantation as a curative method for
      treatment of class III beta-thalassemic patients.

PMID- 15561299
TI  - Differential expression of natural killer cell receptors (CD94/NKG2A) on T cells
      by the stimulation of G-CSF-mobilized peripheral blood mononuclear cells with
      anti-CD3 monoclonal antibody and cytokines: a study in stem cell donors.
AB  - We investigated the expression of the inhibitory NKR (CD94/NKG2A) of the G-CSF
      mobilized peripheral blood mononuclear cells (G-PBMC) on T cells after
      stimulation for 7 days by immobilized anti-CD3 monoclonal antibody (mAb) with or
      without cytokines. We demonstrated increased expression of CD94/NKG2A on
      CD3+/CD8+ T cells. Also, addition of IL-12 induced significantly more CD94/NKG2A
      expression than addition of IL-15: CD94+CD3+/NKG2A+CD3+; 43.8 +/- 11.6%/33.7 +/-
      11.4% by IL-12 versus 32.8 +/- 13.2%/21.3 +/- 9.6% by IL-15, respectively (n = 9,
      P < .05). However, >90% purified CD94+ cells CD94+ obtained from IL-15-treated G
      PBMC by magnetic cell sorting (MACS) exhibited higher cytolytic (CTL) activity
      against K562 cells than that from IL-12-treated G-PBMC: E:T = 20:1, 40.7 +/-
      18.4% vs 15.1 +/- 5.2% (n = 5, P < .05). Therefore, the cytokine effects on
      inhibitory NKR expression on T cells and CTL activity are differently regulated.
      Based on these findings, it may be possible to establish the effective strategy
      to expand inhibitory NKR-expressing T cells with CTL activity for cell therapy.

PMID- 15561300
TI  - The efficiency of muscle contraction.
AB  - When a muscle contracts and shortens against a load, it performs work. The
      performance of work is fuelled by the expenditure of metabolic energy, more
      properly quantified as enthalpy (i.e., heat plus work). The ratio of work
      performed to enthalpy produced provides one measure of efficiency. However, if
      the primary interest is in the efficiency of the actomyosin cross-bridges, then
      the metabolic overheads associated with basal metabolism and excitation
      contraction coupling, together with those of subsequent metabolic recovery
      process, must be subtracted from the total heat and work observed. By comparing
      the cross-bridge work component of the remainder to the Gibbs free energy of
      hydrolysis of ATP, a measure of thermodynamic efficiency is achieved. We describe
      and quantify this partitioning process, providing estimates of the efficiencies
      of selected steps, while discussing the errors that can arise in the process of
      quantification. The dependence of efficiency on animal species, fibre-type,
      temperature, and contractile velocity is considered. The effect of contractile
      velocity on energetics is further examined using a two-state, Huxley-style,
      mathematical model of cross-bridge cycling that incorporates filament compliance.
      Simulations suggest only a modest effect of filament compliance on peak
      efficiency, but progressively larger gains (vis-a-vis the rigid filament case) as
      contractile velocity approaches Vmax. This effect is attributed primarily to a
      reduction in the component of energy loss arising from detachment of cross-bridge
      heads at non-zero strain.

PMID- 15561301
TI  - Axonal excitability revisited.
AB  - The original papers of Hodgkin and Huxley (J. Physiol. 116 (1952a) 449, J.
      Physiol. 116 (1952b) 473, J. Physiol. 116 (1952c) 497, J. Physiol. 117 (1952d)
      500) have provided a benchmark in our understanding of cellular excitability. Not
      surprisingly, their model of the membrane action potential (AP) requires
      revisions even for the squid giant axon, the preparation for which it was
      originally formulated. The mechanisms they proposed for the voltage-gated
      potassium and sodium ion currents, IK, and INa, respectively, have been
      superceded by more recent formulations that more accurately describe voltage
      clamp measurements of these components. Moreover, the current-voltage relation
      for IK has a non-linear dependence upon driving force that is well described by
      the Goldman-Hodgkin-Katz (GHK) relation, rather than the linear dependence on
      driving force found by Hodgkin and Huxley. Furthermore, accumulation of potassium
      ions in the extracellular space adjacent to the axolemma appears to be
      significant even during a single AP. This paper describes the influence of these
      various modifications in their model on the mathematically reconstructed AP. The
      GHK and K+ accumulation results alter the shape of the AP, whereas the
      modifications in IK and INa gating have surprisingly little effect. Perhaps the
      most significant change in their model concerns the amplitude of INa, which they
      appear to have overestimated by a factor of two. This modification together with
      the GHK and the K+ accumulation results largely remove the discrepancies between
      membrane excitability of the squid giant axon and the Hodgkin and Huxley (J.
      Physiol. 117 (1952d) 500) model previously described (Clay, J. Neurophysiol. 80
      (1998) 903).

PMID- 15561302
TI  - Pore-forming protein toxins: from structure to function.
AB  - Pore-forming protein toxins (PFTs) are one of Nature's most potent biological
      weapons. An essential feature of their toxicity is the remarkable property that
      PFTs can exist either in a stable water-soluble state or as an integral membrane
      pore. In order to convert from the water-soluble to the membrane state, the toxin
      must undergo large conformational changes. There are now more than a dozen PFTs
      for which crystal structures have been determined and the nature of the
      conformational changes they must undergo is beginning to be understood. Although
      they differ markedly in their primary, secondary, tertiary and quaternary
      structures, nearly all can be classified into one of two families based on the
      types of pores they are thought to form: alpha-PFTs or beta-PFTs. Recent work
      suggests a number of common features in the mechanism of membrane insertion may
      exist for each class.

PMID- 15561303
TI  - Poly(ADP-ribose) polymerases: homology, structural domains and functions. Novel
      therapeutical applications.
AB  - Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes, which show
      differences in structure, cellular location and functions. However, all these
      enzymes possess poly(ADP-ribosyl)ation activity. Overactivation of PARP enzymes
      has been implicated in the pathogenesis of several diseases, including stroke,
      myocardial infarction, diabetes, shock, neurodegenerative disorder and allergy.
      The best studied of these enzymes (PARP-1) is involved in the cellular response
      to DNA damage so that in the event of irreparable DNA damage overactivation of
      PARP-1 leads to necrotic cell death. Inhibitors of PARP-1 activity in combination
      with DNA-binding antitumor drugs may constitute a suitable strategy in cancer
      chemotherapy. In addition, PARP inhibitors may be also useful to restore cellular
      functions in several pathophysiological states and diseases. This review gives an
      update of the state-of-the-art concerning PARP enzymes and their exploitation as
      pharmacological targets in several illnesses.

PMID- 15561304
TI  - The use of whole genome amplification in the study of human disease.
AB  - The availability of large amounts of genomic DNA is of critical importance for
      many of the molecular biology assays used in the analysis of human disease.
      However, since the amount of patient tissue available is often limited and as
      particular foci of interest may consist of only a few hundred cells, the yield of
      DNA is often insufficient for extensive analysis. To address this problem,
      several whole genome amplification (WGA) methodologies have been developed.
      Initial WGA approaches were based on the polymerase chain reaction (PCR).
      However, recent reports have described the use of non-PCR-based linear
      amplification protocols for WGA. Using these methods, it is possible to generate
      microgram quantities of DNA starting with as little as 1mg of genomic DNA. This
      review will provide an overview of WGA approaches and summarize some of the uses
      for amplified DNA in various high-throughput genetic applications.

PMID- 15561305
TI  - Pakistani adolescents' coping with stress: effect of loss of a parent and gender
      of adolescents.
AB  - The present study examined the effect of parental loss and gender of adolescents
      on their coping with stress. Sample included those adolescents who had either of
      their parents died (N = 40) and those having both living parents (N = 40). It was
      hypothesized that adolescents with one parent alive would differ in their ways of
      coping with stress compared to those who have both living parents. It was also
      hypothesized that there would be gender differences in adolescents' coping.
      Coping Strategies Questionnaire (CSQ, Kausar, 1996) was used to assess
      adolescents' coping. Data was analysed using t-test and multivariate analysis of
      variance (MANOVA). Analyses showed that avoidance-focused coping was the most
      frequently used and active distractive coping was the least frequently used
      strategy by the adolescents. Adolescents with both living parents employed more
      active distractive and religious-focused coping compared to those with one parent
      alive. Girls employed significantly more strategies to cope with stress compared
      to boys. Results also revealed interactive effect of parental loss and gender on
      coping strategies used by adolescents. The findings suggest that death of either
      of the parents and gender of the adolescent is important determinants of the ways
      adolescents deal with stress.

PMID- 15561306
TI  - Suicidal ideation and attempts in adolescents: associations with depression and
      six domains of self-esteem.
AB  - This study aimed to disentangle the influence of depression and self-esteem on
      suicidal behaviour in adolescence. Grades 8 and 11 students in Cape Town, South
      Africa (n = 939) completed questionnaires assessing suicidal ideation and
      behaviour, depression, and self-esteem with respect to family, peers, school,
      sports/athletics, body image and global self-worth. Data were analysed using a
      series of multinomial logistic regression models adjusted for gender, grade, race
      and the sampling strategy. Results indicated that depression and low self-esteem
      in the family context were independently associated with suicide ideation and
      attempts. Moreover, low family self-esteem significantly differentiated suicide
      attempters from ideators. Screening for depression and low self-esteem in the
      family context is discussed as a possible strategy for helping to identify
      adolescents at risk for suicide attempts.

PMID- 15561307
TI  - How adolescents construct their future: the effect of loneliness on future
      orientation.
AB  - This study examined the effect of loneliness, gender, and two dimensions of
      prospective life domains on adolescent future orientation. Future orientation was
      studied in four prospective domains: social relations, marriage and family,
      higher education and work and career. These domains are described in terms of two
      dimensions: theme (relational vs. instrumental) and distance (near vs. distant
      future). Data collected from Israeli Jewish adolescents (11th graders) were
      analysed by repeated measures ANOVAs and ANCOVAs (covariate: depressive
      experiences) for seven future orientation variables: value, expectance, control
      (motivational variables), hopes, fears (cognitive representation variables),
      exploration, commitment (behavioural variables). As predicted, lonely adolescents
      scored lower than socially embedded adolescents on future orientation variables
      applied to the relational and near future domains and lonely boys scored lower
      than lonely girls. However, effects were found only on the three future
      orientation motivational variables and not on the cognitive representation and
      behavioural variables. Contrary to prediction controlling for the effect of
      depressive experiences did not reduce the effect of loneliness on the future
      orientation variables, but reduced the tendency of adolescents to score higher on
      all future orientation variables in the instrumental than in the relational
      prospective domains. The contribution of these findings to the understanding of
      adolescent loneliness and future orientation was discussed and directions for
      future research were suggested.

PMID- 15561308
TI  - Differentiation and test anxiety in adolescents.
AB  - The study tested several propositions about an important construct in Bowen's
      (Family Therapy in Clinical Practice, Aronson, New York, 1978; Family Evaluation,
      Norton, New York, 1988) theory of differentiation, using an Israeli sample of
      adolescents to examine relationships between differentiation of self, family
      differentiation, test anxiety, trait anxiety and cognitive performance. The main
      findings were that family differentiation (specifically, adolescents'
      relationships with their mothers) was negatively correlated with levels of test
      and trait anxiety and positively correlated with cognitive performance. All
      scales of differentiation of self, particularly emotional reactivity and I
      position, were negatively correlated with both types of anxiety. Results suggest
      that differentiation is a meaningful construct for Israeli adolescents, and that
      less differentiated adolescents may be at risk for high levels of test anxiety
      and low levels of cognitive performance. Treatment of test-anxious adolescents
      therefore requires consideration of possible difficulties in individuating and
      differentiating from their families of origin.

PMID- 15561309
TI  - Parenting and adolescent self-regulation.
AB  - This study examined the relationship between adolescents' academic and non
      academic self-regulation (SR), authoritative parenting (as demonstrated by high
      levels of Involvement, Strictness, and Autonomy Granting), and parent self
      efficacy in four areas. Participants were 214 Australian high school students and
      their parents. There was a moderate correlation (r = 0.63) between academic and
      non-academic SR. Adolescents and their parents differed significantly in their
      perceptions of parenting behaviours, with parents rating themselves higher than
      their children on Involvement, Autonomy Granting, and Strictness behaviours. A
      model of the relationships between the constructs was developed showing a strong
      path from parent self-efficacy to both academic and non-academic SR via high
      parental Involvement (as perceived by adolescents). Strict parenting and the
      granting by parents of psychological autonomy to their adolescent children did
      not appear to be important in the development of young people's self-regulatory
      behaviours.

PMID- 15561310
TI  - Development and validation of a depression scale for Asian adolescents.
AB  - Items covering both core and culture-specific facets of depression were generated
      based on literature review and clinical experience. They were modified following
      focus group discussions with depressed adolescents and adolescents in the
      community. The newly constructed Asian Adolescent Depression Scale (AADS) was
      administered to a clinical and a community sample of adolescents together with
      other rating scales. The AADS comprised 4 factors (negative self-evaluation,
      negative affect, cognitive inefficiency and lack of motivation) and demonstrated
      sound psychometric properties. Negative socially oriented self-evaluation and
      cognitive inefficiency were important in Singaporean adolescents'
      conceptualization of depression and are likely to be Asian culture-specific
      dimensions.

PMID- 15561311
TI  - Retrospective and prospective cognitions in adolescents: anxiety, depression, and
      positive and negative affect.
AB  - Research with anxious and depressed adults has suggested that anxiety is related
      to an increased anticipation of both negative memories and negative expectancies
      whereas depression is related to a reduction in positive memories and
      expectancies. The present study examined whether anxiety and depression in 123
      school-aged adolescents would show the same pattern. Small groups completed a
      memory and future thinking task in which they were asked to generate future and
      past, positive and negative events. Adolescents with higher levels of depression
      and those with higher levels of anxiety reported significantly more negative
      events relative to controls, but neither group generated fewer positive events.
      The results provide support for the involvement of cognitions in mood disturbance
      although do not support the idea that these cognitions are different in anxiety
      and depression.

PMID- 15561312
TI  - Pathways to self-esteem in late adolescence: the role of parent and peer
      attachment, empathy, and social behaviours.
AB  - The goal of this study was to examine both the direct and indirect relations of
      parent and peer attachment with self-esteem and to examine the potential
      mediating roles of empathy and social behaviour. 246 college students (M age =
      18.6 years, S.D. = 1.61) completed self-report measures of parent and peer
      attachment, empathy, social behaviour, and self-esteem. Structural equation
      modelling revealed that parental attachment had mostly direct effects on self
      esteem. Among females, the links between peer attachment and self-esteem,
      however, were entirely mediated by empathy and prosocial behaviour. The findings
      from this study suggest that although close supportive relationships with parents
      and peers are related to adolescent self-esteem, these links are complex.

PMID- 15561313
TI  - Leisure activities and problem behaviours among Hungarian youth.
AB  - We examined leisure behaviours and the relationships between leisure and a
      variety of problem behaviours in a sample of 1422 Hungarian adolescents (age
      range: 14-19). Findings from multivariate analyses suggest that some aspects of
      adolescent leisure, such as family or conventional activities, act as protective
      factors against problem behaviours, while peer-oriented activities or commercial
      types of leisure contribute to greater risk for problem behaviours. We also found
      that the same leisure activities explained problem behaviours for both males and
      females. The study suggests that the relationships between leisure activities and
      problem behaviours are highly similar as found among Western youth.

PMID- 15561314
TI  - Perceptions of child support and sexual activity of adolescent males.
AB  - Using the 1995 new cohort of the National Survey of Adolescent Males, this paper
      examines the association between perceptions of child support and adolescent
      males' sexual activity. The results indicate that adolescent males who expect the
      chance of being required to pay child support is high if one becomes a non
      resident father or who has a family member who paid child support before are more
      likely to have the same female sexual partner and less likely to have had two or
      more female partners. Additionally, expectations of being required to pay child
      support and history of a family member paying child support are positively
      associated with contraceptive use, especially for Black adolescents.

PMID- 15561315
TI  - Adolescent drug trafficking trends in the United Kingdom--a 10-year retrospective
      analysis.
AB  - This paper reports data from HM Customs and Excise (HMCE) of recorded cases of
      adolescent drug trafficking through all sea and air points of entry into the UK
      over a 10-year period (May 1992-May 2002). We report the characteristics of 38
      cases of mixed gender and nationality ranging in age between 13 and 18 years who
      have been apprehended by HMCE due to the illegal importation of drugs.
      Highlighted is an increasing trend in UK national male and female adolescents
      being apprehended for drug trafficking. Of particular note is the observation
      that more young adolescent females were apprehended importing large consignments
      of Class A substances than their male counterparts.

PMID- 15561316
TI  - Five years of progress for International Journal of Cardiology.

PMID- 15561317
TI  - Role of angiotensin receptor blockers in patients with left ventricular
      dysfunction: lessons from CHARM and VALIANT.
AB  - The role of angiotensin receptor blockers (ARBs) in patients with left
      ventricular dysfunction has changed after the VALIANT and CHARM trials. CHARM
      proved that candesartan is a good alternative for patients with chronic heart
      failure who cannot tolerate ACE-inhibitors. Moreover, VALIANT demonstrated non
      inferiority of valsartan compared to captopril in patients after an acute
      myocardial infarction. The add-on effects of an ARB on top of an ACE-inhibitor
      are somewhat less pronounced, although a reduction in the number of
      hospitalizations for heart failure seems a consistent finding.

PMID- 15561318
TI  - Reversible myocardial dysfunction: basics and evaluation.
AB  - Large areas of non-functional but viable myocardium with reversible dysfunction
      are commonly seen in patients with acute myocardial infarction. Both reperfusion
      of acutely ischemic myocardium and chronic myocardial ischemia may produce a
      reversible forms of ventricular dysfunction. The two main conditions that lead to
      reversible myocardial dysfunction are stunned myocardium and hibernating
      myocardium. Myocardial stunning represents post-ischemic myocardial dysfunction
      that persists despite restoration of normal flow, with gradual return of
      contractile function. Hibernating myocardium is a state of persistently impaired
      myocardial function at rest due to reduced coronary blood flow owing to residual
      stenosis that can be restored toward normal by revascularization. The success of
      the revascularization procedures depends on the presence of amount of
      dysfunctional but viable myocardium. The basics and evaluation of reversible
      myocardial dysfunction are reviewed.

PMID- 15561319
TI  - Optimal management of hyperlipidemia in primary prevention of cardiovascular
      disease.
AB  - Cardiovascular disease (CVD) in the developed countries continues to grow at an
      epidemic proportion. There are a significant number of young adults with no
      clinical evidence of CVD, but who have two or more risk factors that predispose
      them to CV events and death. Many of these risk factors are modifiable, and by
      controlling these factors, the CVD burden can be decreased significantly. Recent
      statistics have shown that, if all major forms of CVD were eliminated, the life
      expectancy would rise by almost 7 years. Hence it is imperative that primary
      prevention efforts should be initiated at a young age to avert decades of
      unattended risk factors. Hyperlipidemia has been linked to CVD almost a century
      ago. Since then various clinical trials have not only supported this link, but
      have also shown the CV benefits in aggressively treating patients with
      hyperlipidemia. In this generation, we have various therapeutic agents that are
      capable of reducing the elevated lipid levels. With drugs like statins, we are
      able to reduce the risk of CVD by about 30% and avoid major adverse events. Newer
      drugs are being researched and introduced in the treatment of hyperlipidemia in
      humans. These can be used in combination therapy resulting in optimal levels of
      lipids. The new National Cholesterol Education Program (NCEP)/Adult Treatment
      Panel III (ATP III) guidelines have come as a wake-up call to clinicians about
      primary prevention of CVD through strict lipid management and multifaceted risk
      management approach in the prevention of CVD.

PMID- 15561320
TI  - Clinical and pharmacological significance of alpha2-adrenoceptor polymorphisms in
      cardiovascular diseases.
AB  - The alpha2-adrenoceptors (alpha2-ARs) are receptors for endogenous catecholamines
      (norepinephrine and epinephrine) that mediate a number of physiological and
      pharmacological responses such as hypotension and sedation. Three distinct
      subtypes, denoted alpha2A-, alpha2B- and alpha2C-AR, have been characterized and
      cloned. Employment of mutation screening in the study of human populations from
      various ethnic backgrounds has shown that alpha2-AR genes are polymorphic. The
      functional and biochemical consequences of these polymorphisms have been analyzed
      by expressing the wild-type receptors and their respective genetic variants in
      heterologous systems such as CHO and COS-7 cells. Changes include alteration in G
      protein coupling and in agonist-promoted receptor phosphorylation and
      desensitization. Case-control and population-based studies have shown clinical
      association with cardiovascular risk. Further investigation of the genetic
      variants in specialized cells and transgenic animals will provide the molecular
      basis of cardiovascular disease and may reveal alpha2-AR variants as potential
      targets for selective pharmacological interventions.

PMID- 15561321
TI  - Diverse effects of Ace inhibitors and angiotensin II receptor antagonists on
      prevention of cardiac hypertrophy and collagen distribution in spontaneously
      hypertensive rats.
AB  - This study has compared the effects of two structurally different angiotensin
      converting enzyme inhibitors (ACEis) such as zofenopril (Zof, with sulfhydrylic
      group) and lisinopril (Lis, with carboxylic group) and an angiotensin II AT(1)
      receptor antagonist (losartan, Los) on the prevention of cardiac hypertrophy and
      collagen distribution in spontaneously hypertensive rats (SHRs). The SHRs were
      untreated or received: Zof (10 mg/kg/day), Lis (10 mg/kg/day) or Los (20
      mg/kg/day) in drinking water starting at 4 weeks of age. At 8, 16 and 24 weeks of
      age, 8 rats/group were sacrificed for determination of blood pressure, cardiac
      hypertrophy and collagen distribution. All treatments significantly decreased
      blood pressure and cardiac indices, expressed as the ventricles to body weight
      ratio, both variables being significantly correlated. Total ventricular collagen
      content was similarly decreased in all treated groups. Zof significantly
      increased the expression of collagen type III and normalized the collagen type
      I/III ratio. These results suggest that the effects of these drugs on different
      types of collagen are independent from angiotensin II formation. Similar findings
      obtained with captopril seem to indicate that the antioxidant sulfhydrylic group
      of these ACEis can play a role in the distribution of collagen during cardiac
      hypertrophy.

PMID- 15561322
TI  - Regression of left ventricular hypertrophy and improvement of diastolic function
      in hypertensive patients treated with telmisartan.
AB  - OBJECTIVES: The study was designed to test whether or not the angiotensin II
      receptor blocker telmisartan brings about regression of left ventricular (LV)
      concentric hypertrophy and whether or not these changes are associated with
      improved diastolic filling. METHODS: An echocardiographic follow-up study was
      performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mmHg,
      diastolic blood pressure [DBP] >90 mmHg) and mild-to-moderate LV hypertrophy (LV
      mass index related to body surface area [LVMI] 117-150 g/m2 for men and 105-150
      g/m2 for women) treated with telmisartan monotherapy 40-80 mg once daily for 1
      year. Blood pressure, LVMI, left atrial (LA) volumes, and diastolic function were
      determined at baseline and after 3, 6, 9, and 12 months of treatment. Blood
      pressure was also monitored at all visits. Diastolic function was assessed by
      examination of transmitral inflow and pulmonary vein flow patterns. RESULTS:
      Telmisartan reduced blood pressure; after 12 months, the mean+/-S.D. SBP and DBP
      were reduced from 144+/-10 to 126+/-8 mmHg (p<0.001) and from 98+/-8 to 86+/-7
      mmHg (p<0.001), respectively. The LVMI was decreased from 119+/-7 to 109+/-3 g/m2
      (p<0.001) after 12 months' telmisartan treatment. All patients had diastolic
      dysfunction at baseline. After 12 months' telmisartan treatment, a normal pattern
      of transmitral inflow was present in 21% of patients. The regression of LV
      hypertrophy observed after 12 months was associated with increased peak early
      diastolic velocity/peak late diastolic velocity ratio from 0.60+/-0.18 to 0.83+/
      0.20 (p<0.001), shortened isovolumic relaxation time (IVRT) from 110+/-13 to
      105+/-13 ms (p<0.001), and decreased deceleration time from 229+/-30 to 215+/-28
      ms (p=0.002). Univariate analysis showed that shortened IVRT was related to a
      reduction in the LVMI and LA maximal and minimal volumes. In the multivariate
      analysis, the reduction in LVMI and the reduction in LA maximal and minimal
      volumes were independently associated with IVRT reduction. CONCLUSIONS:
      Telmisartan 40-80 mg is effective in LV hypertrophy regression in hypertensive
      patients. The reduction in LVMI due to telmisartan monotherapy was associated
      with a significant improvement of diastolic filling parameters and with a
      significant reduction of LA volumes.

PMID- 15561323
TI  - Absence of ST elevation in ECG leads V7, V8, V9 in ischaemia of non-occlusive
      aetiologies.
AB  - BACKGROUND AND OBJECTIVE: Occlusion of the circumflex coronary artery may present
      with either ST elevation typical of inferior or lateral myocardial infarction, ST
      depression or a normal 12-lead electrocardiogram (ECG). In patients presenting
      with ST depression, concomitant ST elevation in the posterior leads V7, V8 and V9
      is believed to reflect ST-elevation myocardial infarction of the posterior wall.
      However, to be confident of this diagnosis, it is necessary to know that
      posterior ST depression does not occur in acute subendocardial ischaemia. METHODS
      AND RESULTS: We have prospectively recorded leads V7, V8 and V9 simultaneously
      with the standard 12-lead ECG in patients who underwent treadmill stress test.
      Group A consists of 35 patients who showed ischaemic praecordial ST depression in
      their 12-lead ECGs during treadmill stress test and subsequent angiographic
      documentation of significant coronary artery disease. Group B consists of 35
      subjects who showed normal ECG findings during treadmill stress test. In none of
      the Group A or B patients was there ST elevation in leads V7, V8 or V9 either at
      rest or at peak exercise. ST depression was seen in 69% in V7, 31% in V8 and 11%
      in V9 in the Group A patients at peak exercise. CONCLUSION: ST elevation in leads
      V7, V8 and V9 is uncommon in patients presenting with subendocardial ischaemia.
      Therefore, in patients presenting with acute chest pain and ST depression in the
      12-lead ECG, concomitant posterior ST elevation may be a reliable indicator of ST
      elevation posterior MI. This is likely due to circumflex artery occlusion and may
      require thrombolytic therapy.

PMID- 15561324
TI  - Quantitative assessment of infarct size in vivo by myocardial contrast
      echocardiography in a murine acute myocardial infarction model.
AB  - BACKGROUND: In vivo measurement of the infarct size in a small animal model is
      still challenging. The purpose of this study was to evaluate the feasibility of
      quantitative assessment of infarct size by myocardial contrast echocardiography
      (MCE) in the acute myocardial infarction (AMI) model of the rat. METHODS: In 32
      Sprague-Dawley rats with AMI, we measured total myocardial area (TMA) and infarct
      area (IA) of the rats by MCE study (MCE method). They were compared with those of
      postmortem heart measured by planimetry after histochemical staining with
      triphenyl tetrazolium chloride solution (TTC method). Simple TTC staining was
      done in 13 rats (Group 1). To reduce the postmortem change, continuous aortic and
      left ventricular (LV) pressure was loaded during TTC staining in 19 rats (Group
      2). RESULTS: The TMA, IA, and IA/TMA ratio measured by the MCE method were 38.4+/
      3.4 mm2, 18.3+/-0.8 mm2, and 0.37+/-0.02 in Group 1, and 43.7+/-1.8 mm2, 15.8+/
      1.1 mm2, and 0.37+/-0.02 Group 2, respectively. Those measured by the TTC method
      were 66.1+/-2.2 mm2, 29.3+/-1.1 mm2, and 0.44+/-0.01 in Group 1, and 65.9+/-2.5
      mm2, 26.5+/-1.7 mm2, and 0.40+/-0.02 in Group 2, and 65.9+/-2.5 mm2, 26.5+/-1.7
      mm2, and 0.44+/-0.02 in Group 2, respectively. Compared with the TTC method, the
      MCE method underestimated the TMA and IA in both groups (p<0.001). There was no
      difference in TMA and IA between the two groups in both methods. IA/TMA ratio
      showed significant correlation between the two methods in both groups (r=0.85,
      p<0.001). CONCLUSION: The IA/TMA ratio measured by the MCE method may be useful
      for in vivo estimation of the myocardial infarct size in the AMI model of the
      rat.

PMID- 15561325
TI  - Paroxysmal atrioventricular block: clinical experience with 20 patients.
AB  - BACKGROUND: Paroxysmal atrioventricular (AV) block is an ill-defined entity,
      previously described in sporadic cases in association with vasovagal reaction,
      coronary angiography and distal conduction disease. METHODS: We describe 20
      patients (10 women) aged 26 to 80 years with symptomatic paroxysmal AV block.
      RESULTS: Eight patients had ischemic heart disease-three with dilated
      cardiomyopathy, and two with co-existing carotid sinus hypersensitivity. Eight
      were taking chronic AV blockers. In five patients, the paroxysmal AV block
      occurred during a vagal reaction, in one during migranotic headaches, in one
      following aortic valve replacement and in one while recovering from acute
      myocardial infarction. The events lasted between 2.2 and 36 s. In 10 patients,
      the QRS configuration on the electrocardiogram was wide. Immediate treatment
      consisted of intravenous atropine and fluid supplements in two patients,
      discontinuation of the AV blocking agents in four, and the insertion of a
      temporary pacemaker in eight. Seventeen patients required a permanent pacemaker.
      CONCLUSIONS: Paroxysmal AV block is an underestimated clinical entity related to
      vagal reaction, AV blocking drugs and distal conduction disease. Most of our
      patients eventually required implantation of a permanent pacemaker.

PMID- 15561326
TI  - Circadian variation of QTc dispersion in children with vasovagal syncope.
AB  - AIMS: To assess the validity of QTc dispersion to cardiac autonomic nervous
      function status. METHOD AND RESULTS: Prospective comparisons of QTc dispersion
      measurements in 77 neurally mediated cardiac syncope (NMCS) patients (29 boys, 48
      girls, mean age 13.4+/-0.78) were evaluated. Head-up tilt test (HUT) was positive
      in 38 patients and negative in 39 patients. QTc dispersion was significantly
      higher early morning and late night in HUT-positive group compared with HUT
      negative group (p<0.001). Although there was a circadian rhythm in HUT-positive
      group, there was no change on the QTc dispersion within a day in the HUT-negative
      group. QTc dispersion in the HUT-positive group was high in accordance with their
      high sympathetic nervous stimulation. Moreover, QTc dispersion was higher during
      late night and early morning than the rest of the day. CONCLUSION: These results
      may explain why the HUT-positive patients usually have their syncope attacks
      early in the morning. Additionally, we can use QTc dispersion measurement as a
      new noninvasive electrocardiographic test to evaluate cardiac sympathetic nervous
      system in NMCS.

PMID- 15561327
TI  - Implementation of guidelines for management of heart failure in heart failure
      clinic: effects beyond pharmacological treatment.
AB  - BACKGROUND: Patients with heart failure have scarce knowledge of their condition
      and frequently report poor quality of life. In spite of numerous studies showing
      improvement of survival and reduction in hospitalizations, several
      epidemiological studies showed that substantial proportion of patients are not
      receiving appropriate treatment. Intensive multidisciplinary approach can improve
      management of the patients with heart failure. AIM: To assess the efficacy of
      intensive patient management in heart failure clinic with respect to patient
      knowledge, pharmacological management, and quality of life. METHODS: From
      outpatients, visiting the heart failure clinic in period form March 2002 to March
      2003, we prospectively enrolled patients with heart failure due to systolic
      dysfunction. Patient knowledge about their condition was assessed by a knowledge
      questionnaire. Data on their clinical characteristics, diagnostic and
      pharmacological management were analyzed. Quality of life was assessed with
      Minnesota Living with Heart Failure Questionnaire (MLHFQ). Patients rated their
      quality of life and heath on a seven-category descriptive scale from 1 (best) to
      7 (worst). Data are shown as mean (S.D.). RESULTS: In this period we treated 50
      patients (33 men), aged 67 (12) years. Patient knowledge about their condition
      improved after two visits to heart failure clinic (4.8 (1.5) vs. 7.3 (1.4),
      p<0.001). More patients were treated with beta blockers (40% vs. 84%, p<0.001)
      while there was a positive trend for treatment with angiotensin-converting enzyme
      inhibitors (94% vs. 98%) and spironolactone (54% vs. 70%). Equivalent mean daily
      dose of enalapril (11.0 (11.0) mg to 16.7 (8.7) mg, p<0.001) and carvedilol (13.0
      (11.5) mg to 32.1 (18.2) mg, p<0.001) increased. Out-patient management was
      associated with improvement of MLHFQ score (47 (18) vs. 34 (16)), NYHA class (2.9
      (0.4) vs. 2.5 (0.7)), quality of life score (5.3 (1.1) vs. 3.7 (1.0)), and health
      score (5.1 (1.1) vs. 3.7 (1.1)) (p<0.001 for all). CONCLUSIONS: Intensive
      management in heart failure clinic can be effective for translation of guidelines
      into clinical practice. It also improves patient's knowledge and quality of life
      as well as reduces the hospitalizations in heart failure patients.

PMID- 15561328
TI  - How reliable is electrocardiography in differentiating transmural from non
      transmural myocardial infarction? A study with contrast magnetic resonance
      imaging as gold standard.
AB  - Cardiovascular magnetic resonance (CMR) using contrast enhancement allows exact
      determination of the site and transmural extent of myocardial infarction (MI). We
      evaluated whether 12-lead electrocardiography can differentiate transmural from
      non-transmural MI or determine the site of MI by comparing the findings with
      those of contrast-enhanced CMR. A total of 27 patients (59.5+/-12.9 years) with a
      history of MI (6.4+/-2.9 months) underwent CMR (Magnetom, Siemens, Erlangen,
      Germany). Cine images were acquired in the horizontal and vertical long axes and
      short axis by TrueFISP. Contrast-enhanced CMR images were acquired in the same
      axes by segmented FLASH 15 min after administration of gadolinium-DTPA (0.15
      mmol/kg). This showed the MI to be transmural in 11 patients and non-transmural
      in 16. An electrocardiogram (ECG) was recorded in all patients before CMR. T-wave
      alterations, descending ST-depression, pathological Q-waves and absent R waves
      were more frequent in non-transmural MI than transmural MI, as defined by
      contrast-enhanced CMR (p> or =0.618). However, none of the differences were
      statistically significant. R-wave reduction, q waves and horizontal ST-depression
      were more frequent in transmural than in non-transmural MI (p> or =0.157). Again,
      the differences were not significant. The sensitivity of the ECG for MI
      localization was highest in inferior infarctions (85.71%), the specificity was
      highest in anterior infarctions (100%), the best positive predictive value (80%)
      was achieved for anterolateral infarctions, and the best negative predictive
      value for lateral infarctions (95.83%). Transmural and non-transmural MI cannot
      be differentiated by ECG. The ECG is most accurate in detecting anterolateral MI.

PMID- 15561329
TI  - Secular trends and seasonality in first-time hospitalization for acute myocardial
      infarction--a Danish population-based study.
AB  - BACKGROUND: The incidence of acute myocardial infarction has declined in several
      Western countries during the last decades. The incidence and mortality of acute
      myocardial infarction follow a seasonal pattern. We examined if changes in the
      incidence of acute myocardial infarction were associated with any changes in
      seasonality. METHODS: The study was based on 17,989 patients hospitalized with
      first-time acute myocardial infarction identified in the Hospital Discharge
      Registry of the County of North Jutland, Denmark, from 1 January 1983 to 31
      December 1999. The seasonality of acute myocardial infarction was estimated using
      a Poisson regression model. RESULTS: The incidence rate decreased by 3.2% (95%
      confidence interval: 2.7-3.3%) annually. Hospitalizations followed different
      seasonal patterns depending on age, but not on gender. In the <59-year-old group,
      the seasonal pattern was dominated by a broad spring peak (April/May) and a minor
      autumn peak. With increasing age, the spring peak decreased while the autumn peak
      increased and moved towards December. A seasonal pattern dominated by one peak
      (December) and one trough (August) was found in the > or =80-year-old category.
      The shape and extent of these seasonal patterns remained stable throughout the
      study period despite the decline in hospitalizations for acute myocardial
      infarction. CONCLUSION: Hospitalizations for first-time acute myocardial
      infarction decreased from 1983 to 1999, but the seasonal pattern remained stable
      over time.

PMID- 15561330
TI  - High-sensitivity C-reactive protein concentration in a healthy Brazilian
      population.
AB  - BACKGROUND: The use of serum high-sensitivity C-reactive protein (hs-CRP) for
      cardiovascular risk profiling requires knowledge of the distribution in different
      populations. We studied serum hs-CRP in a healthy Brazilian population, with no
      evidence of heart disease, relative to gender and smoking status as well as other
      clinical and laboratory variables. METHODS: 684 healthy Brazilian individuals,
      aged 14-74 years (mean 40.6 years), 295 men (43.1%) and 389 women (56.9%), were
      enrolled between July 1998 and July 2001. The relationship between the log
      transformed hs-CRP, stratified by gender and smoking status (non-smokers,
      smokers), and clinical and laboratory variables were analyzed using the Spearman
      correlation coefficient and multiple linear regression. RESULTS: In a multiple
      linear regression model age (beta=1.0069, p=0.03), body mass index (BMI)
      (beta=1.0093, p<0.01), total cholesterol/HDL cholesterol ratio (TC/HDL-C)
      (beta=1.1015, p<0.01) and heart rate (beta=1.0139, p<0.01) were independently
      correlated with hs-CRP. Stratification according to gender and smoking was able
      to disclose different interactions between these variables and hs-CRP. Variables
      significantly correlated in each stratum were as follows: in smoker men, age
      (beta=1.0236, p=0.04) and TC/HDL-C (beta=1.2065, p<0.01); in non-smoker men, BMI
      (beta=1.0786, p<0.01) and TC/HDL-C (beta=1.1397, p=0.01); in smoker women, BMI
      (beta=1.1006, p=0.03); and in non-smoker women, BMI (beta=1.0873, p<0.01), TC/HDL
      C (beta=1.1405, p=0.01) and heart rate (beta=1.0165, p=0.02). CONCLUSIONS: The
      clinical and laboratory variables studied influenced the concentration of hs-CRP
      according to gender and smoking. In assessing the risk of cardiovascular events
      in relation to serum hs-CRP level, stratification by gender and smoking status is
      indicated.

PMID- 15561331
TI  - Endothelial microparticles correlate with high-risk angiographic lesions in acute
      coronary syndromes.
AB  - BACKGROUND: Endothelial Microparticles (EMP) are small fragments of endothelial
      cell membrane shed during apoptosis or activation. Our group has previously
      reported elevations of EMP in patients with coronary artery disease (CAD),
      thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis
      (MS), and severe hypertension (HTN). In the present study, we evaluate the
      possible relationship between EMP levels and the angiographic severity and
      characteristics of coronary obstructive lesions. METHODS: We studied a total of
      43 patients undergoing coronary angiography. Fifteen had presented with acute
      myocardial infarction (MI), 20 with unstable anginas (UA), 5 with stable angina
      (SA) and 3 with congestive heart failure. Coronary angiography was reviewed and
      coronary lesions were classified using the Ambrose classification. Coronary
      stenoses were classified as high and low risk. High-risk included lesions with
      eccentric appearance (type II), presence of thrombi, or multiple irregularities.
      Low-risk lesions were defined as concentric or type I. Lesions were also analyzed
      by degree of stenosis and history of acute coronary syndrome (ACS). EMP in plasma
      was assayed by flow cytometry. RESULTS: EMP in eccentric type II or multiple
      irregular lesions (high-risk) were 2.5-fold higher than in type I or concentric
      (low-risk) lesions, p<0.05. Lesions with thrombi had three-fold higher EMP than
      those without (p=0.05). Mild stenosis (>20%-<45%) had three-fold higher EMP than
      more severe (>45%), and five-fold higher than those without stenosis (p<0.01).
      Among patients with type II lesions, those with first ACS episode had four-fold
      higher EMP levels than those with recurrent ACS (p<0.01). CONCLUSION: High EMP
      was associated with high-risk angiographic lesions including eccentric type II,
      multiple irregular, and lesions with thrombi. Mild to moderate stenosis was
      associated with higher EMP levels than severe stenosis. EMP may be a useful
      marker in detecting endothelial injury and risk of ACS as defined by angiography.

PMID- 15561332
TI  - Planar myocardial perfusion imaging for evaluation of patients with acute chest
      pain.
AB  - BACKGROUND: Rest single-photon emission computed tomographic (SPECT) perfusion
      imaging identifies acute myocardial ischemia in patients with chest pain in the
      emergency department; however, the costs are high and radioisotopic services are
      usually not available 24 h a day. Planar imaging through a portable gamma camera
      may be useful in this setting. However, planar imaging might be associated with
      less predictive values in comparison with a gated SPECT imaging. We sought to
      evaluate rest planar myocardial perfusion imaging for evaluation and triage of
      patients with suspected acute cardiac ischemia. METHODS: Patients within 6 h of
      chest pain onset and nondiagnostic electrocardiograms (ECGs) underwent planar
      myocardial perfusion imaging. Studies showing perfusion defects were considered
      suggestive of acute coronary syndromes. The results of planar scintigraphy were
      compared with the clinical diagnosis and outcomes. All patients were followed up
      and monitored for the occurrence of major cardiac events 120 days after hospital
      discharge. RESULTS: 71 patients underwent scintigraphy. Twenty-one (30%) patients
      had acute coronary syndromes, 15 (21%) had major cardiac events (8 had myocardial
      infarction and 7 underwent myocardial revascularization). Planar scintigraphy
      demonstrated perfusion defects in 21 patients, 16 (76%) patients with acute
      coronary syndromes, 12 (80%) patients who had major cardiac events and in 7 (88%)
      patients with myocardial infarction. The negative predictive value of planar
      scintigraphy was 90% for diagnosis of acute coronary syndromes and 94% for
      detecting major cardiac events. CONCLUSION: Early planar myocardial perfusion
      imaging allowed rapid and accurate risk stratification of emergency departments
      patients with possible myocardial ischemia and nondiagnostic ECGs.

PMID- 15561333
TI  - Insulin resistance increases circulating malondialdehyde-modified LDL and impairs
      endothelial function in healthy young men.
AB  - BACKGROUND: Endothelial dysfunction is regarded as an early feature of
      atherosclerosis. Both LDL oxidation and insulin resistance play important roles
      in the pathogenesis of atherosclerosis. Recent studies have demonstrated a
      significant association between oxidized LDL and insulin resistance. METHODS: We
      investigated relationships between insulin resistance, circulating
      malondialdehyde-modified (MDA)-LDL, and endothelial function in 36 healthy young
      men. Insulin sensitivity was estimated according to homeostasis model assessment
      of insulin resistance (HOMA-IR); we defined subjects with values of at least 2.5
      as an insulin resistant (n=12) and those with values below 2.5 as insulin
      sensitive (n=24). We evaluated endothelial function by flow-mediated vasodilation
      (FMD) of brachial artery during reactive hyperemia, using high-resolution
      ultrasound. We also measured serum MDA-LDL by a sandwich enzyme-linked
      immunosorbent assay. RESULTS: MDA-LDL was significantly higher (146+/-46 vs.
      101+/-32 IU/l, P=0.002) and FMD was significantly lower (3.94+/-1.53 vs. 5.59+/
      1.62 %, P=0.002) in the insulin-resistant group than in the insulin-sensitive
      group. The resistant group showed a significant inverse correlation between MDA
      LDL and FMD (r=-0.675, P=0.016), while the sensitive group did not (r=0.163, NS).
      By multivariate regression analysis, MDA-LDL and age were determinants of FMD
      (R2=0.766) in the insulin-resistant group, while no variable determined FMD in
      the sensitive group. Nitroglycerin-induced endotheliumindependent dilation was
      similar in both groups. CONCLUSIONS: These results suggest that the production of
      circulating MDA-LDL may be accelerated by insulin resistance, thus impairing
      endothelial function even in healthy young men.

PMID- 15561334
TI  - Low variation and high reproducibility in plaque volume with intravascular
      ultrasound.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) has several advantages compared to
      angiography when evaluating coronary atherosclerosis in the vessel wall. METHODS:
      The accuracy, reproducibility, and short-time spontaneous variation in volume of
      vessel, plaque and lumen were studied by electrocardiographic-gated three
      dimensional (3D) IVUS in 20 male patients with ischaemic heart disease (IHD).
      RESULTS: The study lesions were angiographically insignificant, with a length of
      the analysed segment on 11.4+/-5.9 mm. At baseline the mean minimal lumen
      diameter was 2.41+/-0.59 mm, minimal lumen area 4.82+/-2.38 mm2, and maximal
      plaque burden 65.61+/-9.57%. Mean reference diameter was 3.1+/-0.6 mm. No
      significant changes were observed in volumes of total vessel, lumen or plaque.
      The coefficient of variation (CV) for two volume measurements at baseline was:
      vessel 0.8%, plaque 1.3%, and lumen 1.4%. For measurements recorded at baseline
      and after 12.6+/-1.5 weeks, CV was respectively 3.5%, 3.3% and 6.6%.
      Reproducibility and interobserver and intraobserver variation showed very high
      correlations. A linear correlation was present in percent changes over 12.6+/-1.5
      weeks between vessel volume and lumen volume (r=0.804; p<0.001) and between
      percent changes in plaque volume and vessel volume (r=0.581; p=0.007). No
      correlation was found between changes in plaque volume and lumen volume (r=0.015;
      p=0.950). CONCLUSION: ECG-gated 3D IVUS is a highly reproducible method when
      applied on coronary artery atherosclerosis. CV for lumen volume over 12.6+/-1.5
      weeks is twice that of plaque volume indicating the superiority of the 3D IVUS
      compared to coronary angiography (CAG).

PMID- 15561335
TI  - Elastic properties of the ascending aorta in young children after successful
      coarctoplasty in infancy.
AB  - BACKGROUND: Based on the hypothesis that vascular dysfunction in the ascending
      aorta can cause morbidity, we undertook this study on the elastic properties of
      ascending aorta and left ventricular (LV) function in young children who received
      coarctoplasty in early infancy. METHODS: Blood pressures (BP) in the right arm
      and ascending aortic internal diameters determined by M-mode ultrasound at rest
      and after exercise were measured in 25 patients (mean age, 6.4+/-3 years) and 22
      control subjects (mean age, 5.8+/-2.4 years). Ascending aortic stiffness index
      and distensibility were calculated using BP measurements and ascending aortic
      internal diameters. In addition, LV parameters (systolic and diastolic function,
      mass index) were evaluated. RESULTS: Compared with control subjects, patients had
      increased stiffness index (at rest: 4.87+/-1.94 versus 3.57+/-1.19, P=0.021;
      after exercise: 4.33+/-1.91 versus 3.2+/-1.26, P=0.034) and decreased
      distensibility (at rest: 6.90+/-3.15 versus 8.72+/-2.77, P=0.02; after exercise:
      5.69+/-2.39 versus 7.88+/-3.44 cm2 dyn(-1) 10(-6), P=0.023). BP and LV parameters
      showed no consistent differences between the two groups. In patients,
      distensibility was significantly correlated with systolic BP (at rest: P=0.008;
      after exercise: P=0.014) and pulse pressure (at rest: P=0.013; after exercise:
      P=0.001). CONCLUSIONS: This study suggests that vasculopathy of ascending aorta
      is possible in some young children despite early correction. However, long-term
      tracking study is needed to clarify the significance of the study.

PMID- 15561336
TI  - Mortality from hypertrophic cardiomyopathy in England and Wales: clinical and
      screening implications.
AB  - OBJECTIVES: Hypertrophic cardiomyopathy is considered a relatively common cause
      of death in the young. Screening for the disorder has been advocated, but its
      potential value cannot be assessed because the number of deaths in asymptomatic
      cases in the general population has not been investigated. We determined the
      annual number of deaths (and death rates) from hypertrophic cardiomyopathy in
      England and Wales according to age, sex and the presence or absence of symptoms
      so that an affected individual's risk of dying from the disorder and the
      implications of screening could be assessed. METHODS: Ascertainment of all deaths
      from hypertrophic cardiomyopathy over a 3-year period (1996-1998), using death
      certification data from the Office of National Statistics. Deaths in people
      without symptoms were identified from coroner's reports and correspondence with
      pathologists who conducted the necropsies. RESULTS: There were 184 deaths per
      year from hypertrophic cardiomyopathy in England and Wales (about 15% of all
      deaths from cardiomyopathy) of which one third (65) were in people without
      symptoms. Most (110) of the 184 deaths each year were in people over age 55.
      Under age 55 there were only 37 deaths each year in asymptomatic people, out of
      an estimated 60,000 people with the disorder in the population. Of the 37 deaths,
      14 (20%) occurred in relation to physical activity and 2 after competitive sport.
      CONCLUSIONS: In young people without symptoms hypertrophic cardiomyopathy is
      fairly common (1 in 500) but it rarely causes death; the case-fatality rate is
      about 6 per 10,000 per year. Current risk estimates from the study of patients in
      tertiary referral centers or general hospital clinics (420 and 110 deaths per
      10,000 per year, respectively) are not applicable to asymptomatic people in the
      general population; such people, if incidentally identified can be reassured of
      their low risk of death. Screening would not be worthwhile unless a satisfactory
      test becomes available that can detect those few cases likely to die.

PMID- 15561337
TI  - Influence of ovariectomy and 17beta-estradiol treatment on insulin sensitivity,
      lipid metabolism and post-ischemic cardiac function.
AB  - The purpose of this study was to test whether the insulin sensitivity, lipid
      metabolism and the susceptibility of the heart to ischemia/reperfusion injury are
      modulated by the chronic estrogen status. Rats were ovariectomized (OVX), not
      ovariectomized (sham) or ovariectomized and treated with subcutaneous 17 
      estradiol (30 mug/kg/day, OVX+E2) (n=14-17 per group). Within 3 months after
      operation, body weight, the serum levels of estrogen, glucose, insulin, total
      cholesterol (T-chol), HDL-chol, LDL-cholesterol (LDL-chol), triglycerides (TG)
      and lipoprotein a (Lp(a)) were monitored. Three months after operation, hearts of
      partial rats (n=6-8 per group) were isolated and allowed an initial 20-min
      stabilization period, and then cardiac function was recorded and creatine kinase
      (CK) release in the coronary effluent was measured after 4 h of hypothermic
      ischemia in isolated rat hearts. The experimental results showed that from 2
      weeks after ovariectomy to the end of the study, body weights of OVX were
      significantly higher compared with the other two groups (p<0.05). On weeks 5 and
      9, insulin level of OVX was significantly higher than that of the other two
      groups (p<0.05), whereas it was not different among the three groups on weeks 12
      and 13 (p>0.05). Blood glucose on week 13 was significantly higher in OVX
      (p<0.05). Consequently, Insulin Sensitivity Index (ISI) of OVX was lower than
      that of the other two groups on weeks 5 and 9 (p<0.05), but not on weeks 12 and
      13. Serum values for T-chol, HDL-chol and LDL-chol were not significantly
      different among the three groups within the observing period. On week 13, TG
      level in ovariectomized group was significantly lower than in the sham- and E2
      treated groups (p<0.05). Compared with sham, Lp(a) level was slight increased in
      OVX rats (p<0.05), while it was further increased in E2-treated rats (p<0.05).
      Cardiac function (left ventricular pressure (LVP) and +/-dp/dtmax) of hearts
      removed from OVX rats was depressed, and CK release was markedly increased
      (p<0.05). However, treatment with E2 significantly improved cardiac function, as
      shown by increasing left ventricular pressure,+dp/dtmax and -dp/dtmax, and
      decreased CK release. In conclusion, chronic E2 treatment has some beneficial
      effects on cardiovascular disease (CVD), which come from the results of
      improvement of insulin sensitivity and post-ischemia cardiac function. However,
      the mechanism did not include changes in lipids and lipoproteins. The change in
      Lp(a) level shows that estrogen does not confer cardiovascular protection and may
      increase the risk of stroke.

PMID- 15561338
TI  - Utility of event loop recorders for the management of arrhythmias in young
      ambulatory patients.
AB  - We evaluated the diagnostic yield of event loop recorders in ambulatory patients
      referred for palpitations, dizziness or syncopal events and in whom a previous
      Holter recording was not diagnostic. A total of 96 patients were studied, 50
      (52%) were men and 46 (48%) were women with a mean age of 37+/-10 years. Mean
      duration of the recording was 5.2+/-2.3 days. During the recording period, 24 of
      the 96 patients (25%) remained asymptomatic. Automatic recordings revealed
      significant arrhythmias in four (16.7%) patients, which included two (8.3%) cases
      of atrial fibrillation, one (4.2%) non-sustained ventricular tachycardia (VT) and
      one (4.2%) second degree atrio-ventricular (AV) block. The manual function of the
      recorder was used by 72 (75%) patients while they were symptomatic. Palpitations
      were the most common symptom, which corresponded most frequently to normal sinus
      rhythm (43.1%), followed by sinus tachycardia (16.7%). An arrhythmic substrate
      was found in 29 (40.3%) patients, including 13 (18.1%) with isolated ectopic
      beats of supraventricular and/or ventricular origin, 14 (19.4%) with
      supraventricular tachycardia (SVT) and 2 (2.8%) with second degree AV block. The
      data of our study showed that the ambulatory use of an event loop recorder in
      young patients during a mean period of 5 days was highly useful to elucidate the
      potential cause of their symptoms. The particular use of the manually triggered
      function during symptoms allowed to establish a clear correlation between
      symptoms and arrhythmic events including sinus tachycardia in 75% of patients.

PMID- 15561339
TI  - Prevalence of right ventricular dysplasia-cardiomyopathy in a non-referral
      hospital.
AB  - In a cardiological department of a non-referral hospital responsible for 80,000
      inhabitants with 2500 in-hospital patients and 1500 out-hospital patients per
      year, the prevalence, symptoms and prognosis of arrhythmogenic right ventricular
      dysplasia-cardiomyopathy (ARVD/C) were examined retrospectively. From 1997 to
      2002, ARVD/C was diagnosed in 35 females and 45 males (overall prevalence 1 in
      1000 inhabitants) with a mean age of 45.6 years. Symptoms were chest pain (80%),
      palpitations (60%) and syncopes (30%), and clinical findings were repetitive
      ventricular premature beats (50%), supraventricular arrhythmias (30%),
      ventricular tachycardia (20%), aborted sudden death due to ventricular
      fibrillation (1%), right heart failure (4%), biventricular heart failure (1%) and
      high grade AV nodal block (4%). Endomyocardial biopsies were not performed.
      Aborted sudden death occurred in only one patient (0.3%) before the diagnosis was
      made, annual heart failure rate was 1%. No deaths appeared in a follow-up of 1-5
      (mean 2.4) years with clinical assessment as the basis of diagnosis. The
      prevalence of ARVD/C is much higher and the prognosis better than expected from
      results of reference centers.

PMID- 15561340
TI  - Impaired baroreflex as a cause of chronotropic incompetence during exercise via
      autonomic mechanism in patients with heart disease.
AB  - PURPOSE: It is thought that the mechanisms responsible for impaired chronotropic
      response to exercise are related to disturbance of cardiovascular autonomic
      regulation such as the baroreflex. However, it is still unclear whether the
      baroreflex mechanisms modulate heart rate (HR) responses to exercise via vagal
      and/or sympathetic alteration. We therefore investigated the effects of
      baroreflex sensitivity (BRS) on the exercise HR response in the early phase of
      vagal deactivation and in the later phase of sympathetic excitation via metabolic
      stimulation. METHODS: Twenty-four patients (18 males and 6 females, age 59+/-9
      years) with heart disease underwent symptom-limited treadmill exercise testing
      according to the Bruce protocol, and BRS was measured utilizing the phenylephrine
      method. Subjects were grouped by their resting BRS value: 12 with normal BRS (>
      or =6 ms/mmHg) and 12 with depressed BRS (<6 ms/mmHg). The HR response to
      exercise was assessed using two parameters: the increment in HR during exercise
      and the ratio of HR response to the metabolic reserve (chronotropic index).
      RESULTS: (1) In the patients with depressed BRS, the HR responses within 1 min
      after the start of exercise and from 1 min to peak exercise were attenuated
      compared with those having a normal BRS (15+/-8 vs. 24+/-8 bpm and 36+/-9 vs.
      47+/-15 bpm, respectively). (2) The chronotropic index in the patients with
      depressed BRS was lower than in those with normal BRS (0.50+/-0.14 vs. 0.64+/
      0.08). CONCLUSION: These findings suggest that impaired BRS modulates both the
      parasympathetic influence in early exercise and sympathetic effects in the later
      phase on HR response to exercise.

PMID- 15561341
TI  - Lasting impact on health-related quality of life after a first myocardial
      infarction.
AB  - AIMS: To investigate if the previously reported lack of recovery in Health
      Related Quality of Life (HRQOL), in myocardial infarction, patients, would be
      long lasting. METHODS: Of 72 consecutive patients (19% women) with a mean age of
      59 years, 65 consented to participate in a follow-up 1 and 2 years after their
      first myocardial infarction. HRQOL was assessed by self-administered
      questionnaires (SF-36, Cardiac Health Profile and Zung Depression Inventory).
      RESULTS: For the age group <59 years, there was no statistically significant
      recovery in SF-36 Mental Component Summary scores over time. There were
      improvements in Physical Component Summary scores, from baseline to 12 and to 24
      months (p=0.006 and p<0.001, respectively) and from 6 to 24 months (p=0.044).
      This group reached community norms in Physical Component Summary scores after 2
      years but scored significantly below norms in Mental Component Summary scores
      throughout with an effect size of -0.5 (CI -0.88 to -0.14) at 2 years. In
      patients > or =59 years, no changes took place after 6 months. At 2 years,
      factors Emotional and Social Functioning in the Cardiac Health Profile showed
      statistically significant differences between groups (p=0.03 and p=0.05,
      respectively) demonstrating poorer quality of life in the age group <59 years.
      CONCLUSIONS: In younger patients, a clinically important poorer effect on Health
      Related Quality of life is still present 2 years after an acute myocardial
      infarction.

PMID- 15561342
TI  - Reduction of morbidity by immunoadsorption therapy in patients with dilated
      cardiomyopathy.
AB  - BACKGROUND: In patients with dilated cardiomyopathy (DCM) and severe congestive
      heart failure, immunoadsorption (IA) and subsequent IgG substitution leads to an
      acute and prolonged hemodynamic improvement. Goal of this study was to
      investigate the long-term effect of immunoadsorption on morbidity. METHODS: In a
      retrospective analysis of 34 patients (17 patients who have received
      immunoadsorption therapy and 17 control patients) were included. Inclusion
      criteria were DCM, left ventricular ejection fraction less than 35%, NYHA classes
      II-III. The average time after immunoadsorption was 3.0 years (median 2.3 years).
      Both groups did not differ concerning sex, age, duration of disease, medication,
      baseline ejection fraction and NYHA class. RESULTS: In patients who have received
      immunoadsorption (IA) the days of hospitalisation for congestive heart failure
      per year could be significantly reduced in contrast to the control patients (17.2
      days prior to IA, 4.3 days after IA). Even if the procedural days for
      immunoadsorption were included there was still a significant reduction of
      hospitalisation if IA therapy was longer than 2.5 years ago. The days of
      hospitalisation increased gradually with time during the follow up period. IA
      induced an acute increase in EF (19.8-25.7%, p<0.01 vs. baseline). CONCLUSION: IA
      not only leads to an acute hemodynamic improvement in patients with DCM but may
      also reduce morbidity in these patients during the next 3 years.

PMID- 15561343
TI  - Limited utility of the subcostal view for the echocardiographic evaluation of
      left ventricular mass in epidemiological studies of older persons.
AB  - BACKGROUND: Epidemiological estimates of left ventricular mass are based on
      echocardiographic imaging from the parasternal view, which is often unavailable
      in subjects with obesity or lung disease. This study was undertaken to assess
      whether the subcostal view is a valid alternative to estimate left ventricular
      mass in an unselected older population. METHODS: In a cross-sectional study of
      all the residents in Dicomano, Italy, aged > or =65 years, echocardiography was
      performed with a systematic attempt to obtain both the parastermal and the
      subcostal views. RESULTS: The parasternal view was missing in 73/614
      participants, 48 of whom were imaged from the subcostal view. In participants
      imaged from both views, the subcostal view underestimated left ventricular cavity
      dimension and, consequently, left ventricular mass [79.7 (1.3) vs. 93.3 (1.5)
      g/m2; p<0.001]. Furthermore, the subcostal view was only 25% sensitive for the
      diagnosis of hypertrophy. Several multivariate regression models, developed in an
      equation development subgroup and tested in a validation subgroup, failed to
      correct the prediction of left ventricular mass based on measures taken from the
      subcostal view, also after inclusion of demographic, anthropometric, and
      spirometric covariates. CONCLUSIONS: In unselected older persons, the subcostal
      view does not improve the accuracy of echocardiographic estimation of left
      ventricular mass, which remains biased in epidemiological studies.

PMID- 15561344
TI  - Immunoadsorption in idiopathic dilated cardiomyopathy, a 3-year follow-up.
AB  - OBJECTIVE: Recent studies have shown that immunoadsorption (IA) leads to
      improvements in left ventricular function and in functional status in selected
      patients with idiopathic dilated cardiomyopathy (DCM) and circulating
      autoantibodiesautoantibod. Most of the few studies dealing with this topic
      describe only short-term results. The aim of this study was to ascertain the
      prolonged effects of IA over a period of 3 years. MATERIALS AND METHODS: Our
      study included nine patients with circulating beta1-adrenoreceptor antibodies who
      suffered from idiopathic DCM (left ventricular ejection fraction <30%). IA was
      performed using an adsorber against immunoglobulins (Ig Therasorb, Baxter).
      During therapy and after 3 months, hemodynamic parameters were monitored using a
      Swan-Ganz thermodilution catheter. All patients were monitored under clinical and
      echographical examinations over a period of at least 3 years. RESULTS: During IA
      hemodynamic measurements show increases in both cardiac and stroke volume index
      (from 2.0 (S.E.M. 0.16) to 3.0 (S.E.M. 0.32) l min(-1) m(-2), and from 26.1
      (S.E.M. 2.63) to 38.9 (S.E.M. 3.56) ml/m2, respectively). Hemodynamic
      stabilization was observed after the following 3 months (CI 2.6 (S.E.M. 0.14) l
      min(-1) m(-2), SVI 37.9 (S.E.M. 2.14) ml/m2). After 36 months five patients were
      still alive. Antibody titers increased in patients who deteriorated. The five
      patients who are still alive show an increase in left ventricular ejection
      fraction and no significant increase in antibody titers. CONCLUSION:
      Immunoadsorption may improve short-term hemodynamics as well as long-term follow
      up of patients with severe idiopathic dilated cardiomyopathy. Increase in
      antibody titers is accompanied by deterioration of cardiovascular function.

PMID- 15561345
TI  - Influence of valve prosthesis type on the recovery of ventricular dysfunction and
      subendocardial ischaemia following valve replacement for aortic stenosis.
AB  - BACKGROUND: Long-standing aortic stenosis (AS) causes significant progressive
      left ventricular (LV) dysfunction and may result in subendocardial ischaemia.
      Following aortic valve surgery, LV function may improve and this may be
      accompanied by reversal of ischaemia. There is debate about the differential
      effects of valve substitutes. METHODS: We studied 33 patients with significant AS
      and impaired LV systolic function. Patients underwent trans-thoracic Doppler
      echocardiography and 12-lead electrocardiography pre-operatively, prior to
      discharge from hospital and at 2.5 (range 1.5-3) years follow-up. RESULTS: Twenty
      patients received a stentless valve and 13 a stented valve. No patient had
      significant aortic regurgitation, other valvular disease or coronary artery
      disease. LV fractional shortening (FS) increased from 19+/-6% to 26+/-7% post
      operatively and to 33+/-12% at follow-up in the stentless group (p<0.001). In the
      stented group, no significant change was seen in the post-operative FS, although
      it improved at follow-up and at this point did not differ from the stentless
      group. LV mass fell from 338+/-72 to 265+/-64 g post-operatively and to 170+/-77
      g at follow-up (p<0.001) in the stentless group, whereas in the stented group a
      significant fall was seen only at follow-up (329+/-51 g pre-operatively, 304+/-68
      g post-operatively, 166+/-28 g at follow-up, p=0.01). LV free wall excursion
      increased from 0.8+/-0.3 to 1.1+/-0.4 cm (p=0.05) and to 1.4+/-0.3 cm (p=0.02
      compared with pre-operative values) in the stentless group. In the stented group,
      values were 1.0+/-0.4, 1.0+/-0.3 and 1.3+/-0.2 cm (p=0.05 compared with pre
      operative) at the three time points, respectively. QRS duration fell from 113+/
      36 ms pre-operatively to 99+/-12 ms at follow-up in the stentless group and from
      117+/-28 to 99+/-19 ms in the stented group, p=0.01 for both comparisons. QT
      interval fell from 385+/-54 ms pre-operatively to 366+/-39 ms at follow-up
      (p=0.04) in the stentless group with no significant change in the stented group
      (387+/-52 and 375+/-33 ms, p=0.24). There was reversal of LV strain pattern in 11
      (55%) of the stentless group and 6 (46%) of the stented group and normalisation
      of the inverted U wave in two thirds of patients. CONCLUSION: In patients with AS
      and severe LV dysfunction, there is a more rapid improvement in LV function
      following aortic valve replacement with a stentless prosthesis. Improvements in
      those receiving stented valves appear delayed, although there were no differences
      between the groups in LV function or mass at follow-up. Normalisation of LV free
      wall systolic behaviour, narrowing of the QRS complex and a reduction in the QT
      interval suggest that AS is associated with subendocardial ischaemia that
      reverses following valve replacement.

PMID- 15561346
TI  - Inflammation markers and erythrocyte sedimentation rate but not metabolic
      syndrome factor score predict coronary heart disease in high socioeconomic class
      males: the HDDRISC study.
AB  - OBJECTIVE: To evaluate prediction of coronary heart disease (CHD) by quantitative
      measures of the metabolic syndrome and inflammation in a cohort of high socio
      economic status males. METHODS: Incident CHD was identified in a cohort of 649
      male participants in a company health programme during a mean follow-up of 10.6
      years. Using factor analysis, metabolic syndrome and sub-clinical inflammation
      scores were derived from baseline measurements, which included an oral glucose
      tolerance test-derived measure of insulin resistance. Factor scores were then
      included as predictor variables in a Cox regression analysis of incident CHD.
      RESULTS: Forty-two cases of definite CHD were identified on follow-up. The
      conventional risk factors, cigarette smoking, blood pressure, total cholesterol
      and low HDL cholesterol were clearly distinguished as significant predictors of
      incident CHD. Erythrocyte sedimentation rate was also an independent predictor
      (coefficient 0.0480, z score 2.39, p=0.017). The metabolic syndrome factor
      included insulin resistance, body mass index, serum triglycerides, glucose
      tolerance, serum uric acid and fasting plasma glucose. The inflammation factor
      included serum globulin, blood leukocyte count, low albumin, haemoglobin and
      cholesterol, but not erythrocyte sedimentation rate. The inflammation factor
      score was a significant predictor of CHD (coefficient 0.4601, z score 2.43,
      p=0.015) but the metabolic syndrome factor was not (coefficient 0.2488, z score
      1.24, p=0.2). CONCLUSIONS: Erythrocyte sedimentation rate and a factor analysis
      derived measure of sub-clinical inflammation were important in the development of
      CHD in this relatively low-risk group, but neither metabolic syndrome factor
      score nor its individual components predicted CHD.

PMID- 15561347
TI  - Differentiation of dendritic cells in monocyte cultures isolated from patients
      with unstable angina.
AB  - OBJECTIVE: Dendritic cells (DC) stimulate T-cell proliferation and activation in
      the course of adaptive immunity. Its role in unstable coronary plaque in humans
      is unknown. So we investigated the functional role of DC in patients with
      unstable angina pectoris (US) using human monocyte-derived DC. METHODS: Twenty
      milliliters of blood was drawn from the femoral artery of 20 patients, who
      underwent coronary angiography. Ten patients with a diagnosis of US and 10
      patients with normal CAG were included in the observation and control groups,
      respectively. The mononuclear cells were separated from the peripheral blood and
      cultured in RPMI1640 with supplement of rh GM-CSF and rh IL-4 to induce DC. The
      shape and ultrastructure of DC was analyzed with electronic microscopy. The
      phenotype of DC was analyzed with FACS and the alloantigen presenting capacity of
      DC was evaluated by mixed lymphocyte reaction (MLR). The levels of cytokines in
      allogenic DC/T cell cultures were assayed by ELISA. RESULTS: The expression rate
      of CD86 in patients with US was 30.8+/-3.3%, which was obviously higher than that
      of normal DC (19.4+/-3.0%), P<0.001. The capacity of proliferation of patients DC
      to induce allogenic T cells (OD 1.82+/-1.29), which was obviously higher than
      that of the normal DC (OD 0.81+/-0.41), P<0.005. TNF-alpha (40.05+/-7.15 pg/ml),
      IL-1beta (19.01+/-1.39 pg/ml) and IL-6 (40.80+/-16.04 pg/ml), produced during MLR
      were higher in patients with US than that of normal patients 7.85+/-1.10, 12.18+/
      1.93 and 19.55+/-0.7, respectively, P<0.05. IL-10 (10.94+/-0.56 pg/ml) produced
      during MLR was lower in patients with US than that of normal patients (16.63+/
      3.40 pg/ml), P<0.05. CONCLUSION: Our results suggest that the function of DC in
      patients with US is increased and these activated effects of DC may play a
      primary role in the immune process of plaque rupture.

PMID- 15561348
TI  - Transient complete atrioventricular block after cladribine administration.

PMID- 15561349
TI  - Exercise induced atrio-ventricular (AV) block: important but uncommon phenomenon.

PMID- 15561350
TI  - Anomalous origin of the left coronary artery from the main pulmonary artery
      detected on echocardiographic screening study of newborns.

PMID- 15561351
TI  - Endothelialization of ASD devices for transcatheter closure: possibility or
      reality?

PMID- 15561352
TI  - MRI intra-aortic navigation.

PMID- 15561353
TI  - Questionable dysfunction of a dual-Chamber pacemaker in a 17-year-old female:
      differential diagnoses of missing ventricular beats.
AB  - The case of a 17-year-old female who had been implanted a dual-chamber DDD
      pacemaker because of third-degree atrioventricular block is reported. There is a
      history of continued dizziness and even occasional syncopes. At heart rates of
      111/min to 124/min, 24-h Holter electrocardiography revealed isolated missing
      ventricular beats in an otherwise continuous atrially sensed and triggered,
      ventricularly paced rhythm. Differential diagnoses of a putative pacemaker
      dysfunction are presented, comprising 2:1-block at maximum programmed heart rate,
      intermittent lead fracture, anti-pacemaker-mediated tachycardia algorithm,
      ventricular oversensing, P wave signal undersensing, and atrial oversensing.

PMID- 15561354
TI  - One hundred cases of peripartum cardiomyopathy... and counting: what is going on?

PMID- 15561355
TI  - Pulmonary valve staphylococcal endocarditis in a nondrug addict with alcoholic
      cirrhosis.

PMID- 15561356
TI  - Two cases of giant aneurysm in coronary-pulmonary artery fistula associated with
      atherosclerotic change.
AB  - Giant sacclar aneurysm in a coronary-pulmonary artery fistula is extremely rare.
      In this article, we presented two cases of giant aneurysms in coronary-pulmonary
      artery fistula with atherosclerosis.

PMID- 15561357
TI  - The relation between His bundle and the first septal perforating artery:
      implications for percutaneous transluminal septal myocardial ablation.
AB  - The present study shows that in about 12.4% of subjects the first septal artery
      (FSA) is very near from the His bundle. Routine measurement of His-FSA distance
      during percutaneous transluminal septal myocardial ablation (PTSMA) procedure
      might be helpful to stratify which patient would be at higher risk of developing
      complete AV block.

PMID- 15561358
TI  - Vented gaseous deflagrations modelling of hinged inertial vent covers.
AB  - The model of explosion pressure build up in enclosures with inertial vent covers
      and the CINDY code implementing the model are validated against experiments by
      Hochst and Leuckel (1998) in a 50 m3 vessel with a pair of ceiling-mounted
      upwards-opening hinged doors in a 'butterfly' configuration with surface
      densities of 73 and 124 kg/m2 under conditions of initially quiescent and
      turbulent mixtures. The model and the code are further validated against an
      experiment by Zalosh (1978) in a 33.5 m3 room-like enclosure with a pair of wall
      mounted rectangular doors, in a parallel configuration, each hinged at its bottom
      edge with a surface density of 23.1 kg/m2 and initially quiescent mixture. A
      formula for the torque acting upon a rotating venting door is derived under
      conditions of vent cover jet formation. The vent cover jet effect decreases the
      torque three times compared to an elementary approach valid at the start of vent
      cover movement. It is demonstrated that, similar to translating vent covers, the
      vent cover jet effect is crucial for prediction of interdependent vent cover
      displacement in time and pressure transients.

PMID- 15561359
TI  - Hazard assessment of substances produced from the accidental heating of chemical
      compounds.
AB  - Accidental events concerning process industries can affect not only the staff
      working in, but also the environment and people living next to the factory. For
      this reason a regulation is imposed by the European Community to prevent
      accidents that could represent a risk for the population and the environment. In
      particular, Directive 96/82/CE, the so-called 'Seveso II directive', requests a
      risk analysis involving also the hazardous materials generated in accidental
      events. Therefore, it is necessary to develop simple and economic procedure to
      foresee the hazardous materials that can be produced in the case of major
      accidents, among which the accidental heating of a chemical due to a fire or a
      runaway reaction is one of the most frequent. The procedure proposed in this work
      is based on evolved gas analysis methodology that consists in coupling two
      instruments: a thermogravimetric analyzer or a flash pyrolyzer, that are employed
      to simulate accident conditions, and a FTIR spectrometer that can be used to
      detect the evolved gas composition. More than 40 materials have been examined in
      various accident scenarios and the obtained data have been statistically analyzed
      in order to identify meaningful correlations between the presence of a chemical
      group in the molecule of a chemical and the presence of a given hazardous species
      in the fume produced.

PMID- 15561360
TI  - An evaluation of arsenic release from monolithic solids using a modified semi
      dynamic leaching test.
AB  - Quicklime and quicklime-fly ash-based stabilization/solidification (S/S)
      effectiveness was evaluated by performing semi-dynamic leaching tests (American
      Nuclear Society 16.1). Artificial soil samples, contaminated with arsenic
      trioxide (As2O3) as well as field soil samples contaminated with arsenic (As)
      were tested. The artificial soils were prepared by mixing amounts of kaolinite or
      montmorillonite with fine quartz sand. The S/S effectiveness was evaluated by
      measuring effective diffusion coefficients (De) and leachability indices (LX).
      Treatment was most effective in kaolinite-based artificial soils treated with
      quicklime and in quicklime-fly ash treated field soils. The experimental results
      indicate that De values were lowered as a result of S/S treatment. Upon treatment
      LX values were higher than 9, suggesting that S/S treated soils are acceptable
      for "controlled utilization". Based on a model developed by de Groot and van der
      Sloot [G.J. de Groot, H.A. van der Sloot, in: T.M. Gilliam, C.C. Wiles (Eds.),
      Stabilization and Solidification of Hazardous, Radioactive, and Mixed Wastes,
      vol. 2, ASTM STP 1123, ASTM, PA, 1992, p. 149], the leaching mechanism for all of
      the treated soils was found to be controlled by diffusion. The effect of soluble
      silica (Si) on As leachability was also evaluated. When soluble Si concentration
      was less than 1 ppm, As leachability was the lowest. The controlling mechanism of
      As immobilization whether sorption, precipitation, or inclusion was also
      evaluated. It was determined that precipitation was the dominant mechanism.

PMID- 15561361
TI  - Degradation of chlorpyrifos contaminated soil by bioslurry reactor operated in
      sequencing batch mode: bioprocess monitoring.
AB  - Bioslurry reactor (SS-SBR) was studied for the degradation of chlorpyrifos
      contaminated soil using native mixed microflora, by adopting sequencing batch
      mode (anoxic-aerobic-anoxic) operation. Reactor operation was monitored for a
      total cycle period of 72 h consisting of 3 h of FILL, 64 h REACT, 2 h of SETTLE,
      and 3 h of DECANT with chlorpyrifos concentrations of 3000 micrpg/g, 6000
      microg/g and 12000 microg/g. At 3000 microg/g of chlorpyrifos concentration, 91%
      was degraded after 72 h of the cycle period, whereas in the case of 6000 microg/g
      of chlorpyrifos, 82.5% was degraded. However, for 12000 microg/g of chlorpyrifos,
      only 14.5% degradation was observed. The degradation rate was rapid at lower
      substrate concentration and 12000 microg/g of substrate concentration was found
      to be inhibitory. Chlorpyrifos removal rate was slow during the initial phase of
      the sequence operation. Half-life of chlorpyrifos degradation (t0.5) was
      estimated to be 6.3 h for 3000 microg/g of substrate, 17.5 h for 6000 microg/g
      and 732.2 h for 12000 microg/g. Process performance was assessed by monitoring
      chlorpyrifos concentration and biochemical process parameters viz., pH, oxidation
      and reduction potential (ORP), dissolved oxygen (DO), oxygen consumption rate
      (OCR) and microbial count (CFU) during sequence operation. From the experimental
      data obtained it can be concluded that the rate-limiting step with the bioslurry
      phase reactor in the process of chlorpyrifos degradation may be attributed to the
      concentration of substrate present in either soil or liquid phase. Periodic
      operations (SBR) by varying individual components of substrate with time in each
      process step place micro-organisms under nutritional changes from feast to famine
      and maintains a wide distribution in the population of micro-organisms resulting
      in high uptake of the substrate in the bioslurry reactor.

PMID- 15561362
TI  - Oxidation of cyanide in aqueous solution by chemical and photochemical process.
AB  - Cyanide waste is found predominantly in industrial effluents generated from
      metallurgical operations. The toxicity of cyanide creates serious environmental
      problems. In this paper, oxidation of cyanide in aqueous solution was
      investigated using chemical and photochemical process. Chemical oxidation was
      studied at room temperature using H2O2 as oxidant and Cu2+ as catalyst.
      Photochemical oxidation was studied in an annular type batch photoreactor of 1l
      capacity using 25 W low-pressure (81.7% transmission at 254 nm wavelength)
      ultraviolet (UV) lamp along with H2O2 as oxidant. The effect of Cu2+ catalysis
      was also studied. It was observed that in absence of UV source, the degradation
      of cyanide by H2O2 alone was very slow, whereas copper ions accelerated the rate
      of reaction thereby acting as catalyst. Copper formed a complex with cyanide ion,
      i.e. tetracyanocuprate which had greater affinity for H2O2. Cyanate hydrolysis
      was also favoured by copper ions. As Cu2+ ion concentration was increased, rate
      of degradation also increased. Photochemical oxidation by H2O2 and Cu2+ was found
      to be the best system for cyanide degradation. CN- (100 mg/l) was degraded to non
      detectable level in 9 min at pH 10.0 with optimum H2O2 dose of 35.5 mM and Cu2+
      dose of 19 mg/l. Reaction kinetics of cyanide oxidation was found to be pseudo
      first order and the rate constant has been determined for different processes.

PMID- 15561363
TI  - Coagulation-flocculation-decantation of dye house effluents: concentrated
      effluents.
AB  - The treatment and valorization (recycling of water and mineral salts) of dyeing
      effluents constitutes a major economic and environmental issue. Cotton dyeing
      using reactive dyes is actually the most polluting in terms of discharge. In
      order to treat and valorize the effluent from a dyeing process using reactive
      dyes, the firm Clariant and the LPPE have developed and patented a process
      allowing the recovery of most of the water and salts present in the effluent and
      also of a concentrate containing the hydrolyzed reactive dyes and the highly
      concentrated auxiliaries. This paper describes the coagulation-flocculation
      decantation process used to optimize water recovery from the concentrate.
      Coagulants and flocculants are used in the industry for the treatment of
      effluents produced by the synthesis of dyes in general (acid, disperse,
      reactive). Although the settling velocity is relatively low, the results show
      that it is possible to recycle a great volume of water using a small decanter
      area, since the concentrate flow rate is low. These effluents are substantially
      discolored, it possible to envisage recycling them.

PMID- 15561364
TI  - Stabilisation of heavy metal containing dusts by reaction with phosphoric acid:
      study of the reactivity of fly ash.
AB  - Water-washed fly ash was reacted with phosphoric acid in order to transform
      available heavy metals into insoluble metal phosphate compounds. The temperature,
      pH and concentration of free phosphate were monitored during the first 80 min of
      reaction. Phosphoric acid reacted rapidly with second order kinetics and an
      apparent rate constant of 0.015 l/(mol s m2). Analysis of the evolution of the
      concentrations of other major elements of fly ash shows that the reaction follows
      a dissolution-precipitation type mechanism. The solubility of trace heavy metals
      tends to increase at low pH values. Various heat and mass transfer coefficients
      are derived and help understand the phosphate stabilisation procedure and design
      industrial reactors for this purpose. Calcium phosphates are formed which can
      trap heavy metals in a stable apatite mineral structure.

PMID- 15561365
TI  - Treatment of silica effluents: ultrafiltration or coagulation-decantation.
AB  - In the electronics industry, the preparation of silicon plates generates
      effluents that contain a great amount of colloidal silica. Two processes-
      decantation and ultrafiltration--are studied with in view the treatment of the
      effluents released by the firm Rockwood Electronic Materials. The feasibility of
      each of the two processes is studied separately and their operating parameters
      optimized. Both processes allow the recovery of a great proportion of the initial
      effluent (over 89%) as transparent and colorless water that can be reused at the
      start of a line. In view of the results and of the compared advantages and
      disadvantages of the two processes, ultrafiltration will be selected for the
      industrial unit.

PMID- 15561366
TI  - The containment of oil spills in unconsolidated granular porous media using
      xanthan/Cr(III) and xanthan/Al(III) gels.
AB  - The gelation in situ of aqueous solutions of the biopolymer xanthan gum may be a
      method for temporarily containing oil spills in soil whilst the remediation
      procedure is planned and accomplished. The gelling reaction has been carried out
      using as crosslinking agents either Cr(III) or Al(III) cations. By using Cr(III)
      the gelation time, which has been measured for a range of xanthan and/or Cr(III)
      concentrations, is of the order of the hour. On the contrary, the gelation by
      means of Al(III) cations takes place at quite low pH and is instantaneous.
      Therefore, depending on the crosslinker adopted, rather different techniques must
      be used for generating the gel structure in situ. The gels have proven to be
      suitable for the containment of water and of many hydrocarbons without loosing
      their strength even for a long period of time. The rheological properties of
      xanthan aqueous solutions evidence a shear-thinning behaviour that is most
      favourable for the application. Theoretical considerations have permitted the
      establishment of the mobility conditions of xanthan solutions in porous media
      before the gelation, and the estimation of a suitable injection pressure. The
      experiments for investigating the mobility of xanthan solutions in porous media,
      and for simulating the containment of an oil spill, have been done using packed
      beds of uniformly sized spherical glass beads, in glass columns. The glass
      assembly made it possible to visualize the evolution of the phenomena of
      interest.

PMID- 15561367
TI  - Stabilized leachates: sequential coagulation-flocculation + chemical oxidation
      process.
AB  - The combined sedimentation-chemical oxidation treatment of medium-stabilized
      landfill leachates has been investigated. The sequence of stages implemented was:
      (a) coagulation-flocculation by pH decrease (pH 2) to acidic conditions (COD
      removal approximately 25% related to COD0 approximately 7500 ppm); (b)
      coagulation-flocculation by Fe(III) addition (0.01 M) at pH 3.5 (COD removal
      approximately 40% related to COD of supernatant after step (a); (c) Fenton
      (Fe(III) = 0.01 M; H2O2 = 1.0 M) oxidation (COD removal approximately 80% related
      to COD of supernatant after step (a); and (d) coagulation-flocculation of
      Fenton's effluent at pH 3.5 (COD removal approximately 90% related to COD of
      supernatant after step (a). The use of Kynch theory allows for the design of
      clarifiers based on the amount of solids fed. For a general example of 1000 m3
      day(-1) of a feeding stream, clarifier area values of 286,111 and 231 m2 were
      calculated for compacting indices of 3.7, 2.67 and 2.83 corresponding to the
      first, second and third consecutive sedimentation processes, respectively, (steps
      (a), (b) and (d)).

PMID- 15561368
TI  - Red mud addition in the raw meal for the production of Portland cement clinker.
AB  - The aim of the present research work was to investigate the possibility of adding
      red mud, an alkaline leaching waste, which is obtained from bauxite during the
      Bayer process for alumina production, in the raw meal for the production of
      Portland cement clinker. For that reason, two samples of raw meals were prepared:
      one with ordinary raw materials, as a reference sample ((PC)Ref), and another
      with 3.5% red mud ((PC)R/M). The effect on the reactivity of the raw mix was
      evaluated on the basis of the unreacted lime content in samples sintered at 1350,
      1400 and 1450 degrees C. Subsequently, the clinkers were produced by sintering
      the two raw meals at 1450 degrees C. The results of chemical and mineralogical
      analyses as well as the microscopic examination showed that the use of the red
      mud did not affect the mineralogical characteristics of the so produced Portland
      cement clinker. Furthermore, both clinkers were tested by determining the
      grindability, setting time, compressive strength and expansibility. The hydration
      products were examined by XRD analysis at 2, 7, 28 and 90 days. The results of
      the physico-mechanical tests showed that the addition of the red mud did not
      negatively affect the quality of the produced cement.

PMID- 15561369
TI  - Kinetic study of the thermal dehydration of borogypsum.
AB  - In Turkey, a large amount of borogypsum waste is discharged by the economically
      important boric acid industry. Calcination of this waste provides a promising
      technique not only for recovering an economic value but also for reducing its
      environmental impact. The aim of this work is to study the thermal behavior of
      borogypsum, which contains gypsum crystals, boron oxide and some impurities under
      nonisothermal conditions in air atmosphere by using thermogravimetry and
      differential thermal analysis techniques (TG-DTA). Experiments were carried out
      at temperatures ranging from ambient to 773 K at different heating rates. The
      temperatures of conversion from gypsum to hemihydrate and anhydrite states were
      determined. Various methods were used to analyze the TG and DTA data for
      determination of reaction kinetics. The activation energy and frequency factor
      were calculated for dehydration of borogypsum. Activation energy values of the
      main dehydration reaction of borogypsum were calculated to be approximately 95
      114 kJ mol(-1).

PMID- 15561370
TI  - Recovery of EDTA from complex solution using Cu(II) as precipitant and Cu(II)
      subsequent removal by electrolysis.
AB  - Ethylendiaminetetraacetate (EDTA) is a chelating agent widely used in industry
      and agriculture. Resistant to chemical and biological degradation EDTA represents
      a serious ecological problem. In order to avoid the outlet into the environment a
      new method of EDTA recycling has been proposed. The method involves substituting
      of the metal ions in EDTA complexes by Cu(II) and formation of an insoluble
      Cu2EDTA.4H2O compound at the excess of Cu(II) ions in weakly acidic solutions.
      Cu(II) ions substitute such metal ions as Ni(II), Zn(II), Co(II), Cd(II), Ca(II)
      and Mg(II). After treatment of the precipitate with water only, acidic or
      alkaline solutions the copper from the suspension formed can be removed by
      electrolysis. The highest current efficiency under galvanostatic conditions is in
      alkaline solutions, however, the highest yield of EDTA recovery is in acidic
      solutions. FT-IR investigations and chemical analysis of the precipitate formed
      have shown that in acidic and in alkaline solutions, H4EDTA and Na2H2EDTA.2H2O
      were formed, respectively. Electrolysis in acidic solutions gives the best
      results, i.e. the formed H4EDTA contains the highest amount of EDTA (95%) and the
      lowest amount of copper (0.01%).

PMID- 15561371
TI  - Biosorption of cesium by native and chemically modified biomass of marine algae:
      introduce the new biosorbents for biotechnology applications.
AB  - Biosorption batch experiments were conducted to determine the cesium binding
      ability of native biomass and chemically modified biosorbents derived from marine
      algae, namely ferrocyanide algal sorbents type 1 and type 2 (FASs1 and FASs2).
      The applicability of the Langmuir and Freundlich isotherms for representation of
      the experimental data was investigated. The cesium sorption performances of the
      various types of sorbents were compared using the maximum capacities (qmax
      values) obtained from fitting the Langmuir isotherm to the values calculated from
      the sorption experiments, which FASs type 1 and type 2 showed better sorption
      performances for cesium. FASs1 and FASs2 derived from formaldehyde and
      glutaraldehyde crosslinked Padina australis exhibited lower sorption capacities
      than those prepared from the non-crosslinked one. Most of the cesium ions were
      bound to FASs1, derived from Sargassum glaucescens and P. australis, in < 2 min
      and equilibrium reached within the first 30 min of contact. Biosorption of cesium
      by FASs1 derived from P. australis and Cystoseria indica was constantly occurred
      at a wide range of pH, between 1 and 10, and the highest removal took place at pH
      4. The presence of sodium and potassium at 0.5 and 1mM did not inhibit cesium
      biosorption by algae biomass. The maximum cesium uptake was acquired using the
      large particles of FAS2 originated from S. glaucescens (2-4 mm). Desorption of
      cesium from the metal-laden FASs1 (from P. australis, S. glaucescens and Dictyota
      indica) was completely achieved applying 0.5 and 1 M NaOH and KOH, although the
      cesium sorption capacity of the biosorbents (from C. indica and S. glaucescens)
      decreased by 46-51% after 9 sorption-desorption cycles.

PMID- 15561372
TI  - Sorption of acid red 57 from aqueous solution onto sepiolite.
AB  - Sepiolite, a highly porous mineral, is becoming widely used as an alternative
      material in areas where sorptive, catalytic and rheological applications are
      required. High ion exchange capacity and high surface area and more importantly
      its relatively cheap price make it an attractive adsorbent. In this study, the
      adsorption of acid red 57 by natural mesoporous sepiolite has been examined in
      order to measure the ability of this mineral to remove coloured textile dyes from
      wastewater. For this purpose, a series of batch adsorption tests of acid red 57
      from aqueous sepiolite solutions have been systematically investigated as a
      function of parameters such as pH, ionic strength and temperature. Adsorption
      equilibrium was reached within 1h. The removal of acid red 57 decreases with pH
      from 3 to 9 and temperature from 25 to 55 degrees C, whereas it increases with
      ionic strength from 0 to 0.5 mol L(-1). Adsorption isotherms of acid red on
      sepiolite were determined and correlated with common isotherm equations such as
      Langmuir and Freundlich models. It was found that the Langmuir model appears to
      fit the isotherm data better than the Freundlich model. The physical properties
      of this adsorbent were consistent with the parameters obtained from the isotherm
      equations. Approximately, 21.49% weight loss was observed. The surface area value
      of sepiolite was 342 m2 g(-1) at 105 degrees C, and it increased to 357 m2 g(-1)
      at 200 degrees C. Further increase in temperature caused channel plugging and
      crystal structure deformation, as a result the surface area values showed a
      decrease with temperature. The data obtained from adsorption isotherms at
      different temperatures have been used to calculate some thermodynamic quantities
      such as the Gibbs energy, heat and entropy of adsorption. The thermodynamic data
      indicate that acid red 57 adsorption onto sepiolite is characterized by physical
      adsorption. The dimensionless separation factor (RL) have shown that sepiolite
      can be used for removal of acid red 57 from aqueous solutions. The sorption
      capacity of the sepiolite is comparable to the other available adsorbents, and it
      is quite cheaper.

PMID- 15561373
TI  - Atomization of liquids in a Pease-Anthony Venturi scrubber. Part II. Droplet
      dispersion.
AB  - Droplet distribution is of fundamental importance to the performance of a Venturi
      scrubber. Ensuring good liquid distribution can increase performance at minimal
      liquid usage. In this study, droplet dispersion in a rectangular Pease-Anthony
      Venturi scrubber, operating horizontally, was examined both theoretically and
      experimentally. The Venturi throat cross-section was 24 mm x 35 mm, and the
      throat length varied from 63 to 140 mm. Liquid was injected through a single
      orifice (1.0 mm diameter) on the throat wall. This arrangement allowed the study
      of the influence of jet penetration on droplet distribution. Gas velocity at the
      throat was 58.3 and 74.6 m/s, and the liquid flow rate was 286, 559 and 853
      ml/min. A probe with a 2.7 mm internal diameter was used to isokinetically remove
      liquid from several positions inside the equipment. It was possible to study
      liquid distribution close to the injection point. A new model for droplet
      dispersion, which incorporates the new description of the jet atomization process
      developed by the present authors in the first article of this series, is proposed
      and evaluated. The model predicted well the experimental data.

PMID- 15561374
TI  - Biological treatability of raw and ozonated penicillin formulation effluent.
AB  - In the present study, oxidative pre-treatment of pharmaceutical wastewater
      originating from the formulation of the penicillin Sultamycillin Tosylate
      Diydrate via ozonation at varying pH and ozone feed rates was investigated.
      Biological treatability studies were performed with a synthetic wastewater alone
      and supplemented with raw and ozonated penicillin formulation effluents. The
      highest COD (34%) and TOC (24%) removal efficiencies were obtained at pH 11.0,
      whereas the BOD5 value increased from 16 mg l(-1) to 128 mg l(-1) after 40 min of
      ozonation, corresponding to an applied ozone dose of 1670 mg l(-1) and 33%
      relative ozone absorption. The studies showed that no degradation of raw
      penicillin fraction (30% of total COD) occurred, and degradation of the synthetic
      wastewater being completely treatable without penicillin addition, was inhibited
      by 7%. Upon 40 min ozonation, the synthetic wastewater could be completely
      oxidized and at the same time 35% of ozonated penicillin wastewater removal was
      obtained. Respirometric studies were conducted in parallel and produced results
      indicating a 22% decrease in the total oxygen consumption rate established for
      raw penicillin formulation effluent compared to the results obtained from the
      aerobic batch reactor. No inhibition of the synthetic fraction was observed for
      the 40 min-ozonated penicillin formulation effluent, biodegradability of the 60
      min-ozonated penicillin effluent decreased possibly due to recalcitrant oxidation
      product accumulation. The modeling study provided experimental support and
      information on inhibition kinetics in activated sludge model no. 3 (ASM3) by
      means of respirometric tests for the first time.

PMID- 15561375
TI  - Use of poultry litter for biodegradation of soil contaminated with 2,4- and 2,6
      dinitrotoluene.
AB  - Pseudomonas sp. and Pseudomonas putida can utilize dinitrotoluene (DNT) as N
      source after the enzymatic removal of nitro groups from the aromatic ring.
      Addition of nutrients is known to stimulate the biodegradation process. Poultry
      litter has consortia of microorganisms (including Pseudomonas) along with many
      nutrients. The objective of this research was to study the biodegradation of 2,4-
      and 2,6-DNT contaminated soil (from Badger Army Ammunition Plant) using poultry
      litter. Complete biodegradation of both 2,4- and 2,6-DNT in the soil was observed
      after 1-day interaction with poultry litter. No degradation was observed using
      autoclaved litter.

PMID- 15561376
TI  - Discogenic pain.

PMID- 15561377
TI  - Control of inflammatory pain by chemokine-mediated recruitment of opioid
      containing polymorphonuclear cells.
AB  - Opioid-containing leukocytes can counteract inflammatory hyperalgesia. Under
      stress or after local injection of corticotropin releasing factor (CRF), opioid
      peptides are released from leukocytes, bind to opioid receptors on peripheral
      sensory neurons and mediate antinociception. Since polymorphonuclear cells (PMN)
      are the predominant opioid-containing leukocyte subpopulation in early
      inflammation, we hypothesized that PMN and their recruitment by chemokines are
      important for peripheral opioid-mediated antinociception at this stage. Rats were
      intraplantarly injected with complete Freund's adjuvant (CFA). Using flow
      cytometry, immunohistochemistry, and ELISA, leukocyte subpopulations, chemokine
      receptor (CXCR2) expression on opioid-containing leukocytes and the CXCR2 ligands
      keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2)
      and cytokine-induced neutrophil chemoattractant-2 (CINC-2) were quantified. Paw
      pressure threshold (PPT) was determined before and after intraplantar and
      subcutaneous injection of CRF with or without naloxone. PMN depletion was
      achieved by intravenous injection of an antiserum. Chemokines were blocked by
      intraplantar injection of anti-MIP-2 and/or anti-KC antiserum. We found that at 2
      h post CFA (i) intraplantar but not subcutaneous injection of CRF produced dose
      dependent and naloxone-reversible antinociception (P<0.05, ANOVA). (ii) Opioid
      containing leukocytes in the paw and CRF-induced antinociception were reduced
      after PMN depletion (P<0.05, t-test). (iii) Opioid-containing leukocytes mostly
      expressed CXCR2. MIP-2 and KC, but not CINC-2 were detectable in inflamed but not
      in noninflamed tissue (P<0.05, ANOVA). (iv) Combined but not single blockade of
      MIP-2 and KC reduced the number of opioid-containing leukocytes and peripheral
      opioid-mediated antinociception (P<0.05, t-test; P>0.05, ANOVA). In summary, in
      early inflammation peripheral opioid-mediated antinociception is critically
      dependent on PMN and their recruitment by CXCR2 chemokines.

PMID- 15561378
TI  - Pavlovian conditioning of muscular responses in chronic pain patients: central
      and peripheral correlates.
AB  - A differential conditioning design using an aversive slide as conditioned
      stimulus (CS(+)) that was followed by an intracutaneous electric stimulus to the
      left index finger as unconditioned stimulus (US) and a pleasant slide that was
      not followed by shock (CS(-)) were used to test the hypothesis of enhanced
      aversive conditioning of muscular responses in chronic back pain patients (CBP).
      Heart rate, skin conductance levels, and integrated surface electromyograms (EMG)
      from the left and right m. flexor digitorum, the right m. trapezius, and
      bilaterally from the m. orbicularis oculi were recorded. The electroencephalogram
      (EEG) was measured from nine electrode positions. The CBP patients showed an
      enhanced muscular response of the left forearm (where the US was applied) to the
      CS(+) already in the preconditioning phase. During acquisition both the left
      forearm and the right trapezius of the patients but not the controls displayed
      enhanced muscular responding to the CS(+). During extinction the CBP patients'
      muscular responses to both CS(+) and CS(-) were elevated. The contingent negative
      variation of the EEG differentiated between CS(+) and CS(-) in the healthy
      controls but not the chronic pain patients. These data confirm the hypothesis of
      enhanced muscular responding in chronic pain patients and suggest a dissociation
      of muscular and central processes during aversive conditioning in the patients
      that might contribute to the chronicity problem.

PMID- 15561379
TI  - Gender is a confounding factor in pain trials: women report more pain than men
      after arthroscopic surgery.
AB  - A gender difference in the incidence of acute pain may be a confounder in
      analgesic trials. We have tested the hypothesis that the incidence of acute pain
      after knee arthroscopic procedures is greater in women than men. We performed
      three RCTs on intra-articular analgesics in which no postoperative analgesia was
      given until the need for such treatment was documented by scoring moderate-to
      severe pain on a verbal rating scale (VRS 0-4; n=219), and a 0-100 mm visual
      analogue pain scale (VAS) within 2 h postoperatively. All trials were performed
      with an intra-articular catheter technique. The design allowed us to study the
      natural course of pain after arthroscopic surgery until analgesia was required.
      Women reported more pain of at least moderate intensity than men (84 vs 57%;
      P<0.0001), indicating that being female is a risk factor for early postoperative
      pain (RR 1.47, 95% confidence interval from 1.23 to 1.74). The VAS score
      corresponding to moderate and severe pain is similar in men and women. Only short
      acting anaesthetics were given in order to minimise carry-over effects. Since
      previous trials on arthroscopic analgesics neither measured baseline pain nor
      stratified for gender, a difference between treatment groups could result from an
      uneven distribution regarding these factors. Our findings have major implications
      for the interpretation of previously published trials on intra-articular
      analgesia.

PMID- 15561380
TI  - Development and validation of the Pain Treatment Satisfaction Scale (PTSS): a
      patient satisfaction questionnaire for use in patients with chronic or acute
      pain.
AB  - The purpose of this study was to develop and validate a measure of patient
      satisfaction for patients receiving treatment for either acute or chronic pain:
      the Pain Treatment Satisfaction Scale (PTSS). Development of the initial
      questionnaire included a comprehensive literature review and interviews with
      patients, physicians and nurses in the United States, Italy and France. After
      initial items were created, psychometric validation was run on responses from 111
      acute pain and 89 chronic pain patients in the United States. Analyses included
      principal components factor analysis tests of reliability, clinical validity and
      confounding. The hypothesized structure of the questionnaire was supported by
      statistical analyses, and seven overlapping or inconsistent items were removed.
      The multi-item domains of the final PTSS included 39 items grouped in five
      dimensions: information (5 items); medical care (8 items); impact of current pain
      medication (8 items); satisfaction with pain medication which included the two
      subscales medication characteristics (3 items) and efficacy (3 items); and side
      effects (12 items). Internal consistency reliability coefficients were good
      (ranging from 0.83 to 0.92). The test-retest reliability coefficients (ranging
      from 0.67 to 0.81) were good for all dimensions except medication characteristics
      (0.55). All dimensions except medical care discriminated well according to pain
      severity. The satisfaction with efficacy dimension, hypothesized to change in the
      acute pain population, indicated good preliminary responsiveness properties
      (effect size 0.37; P<0.001). The PTSS is a valid, comprehensive instrument to
      assess satisfaction with treatment of pain based on independent modules that have
      demonstrated satisfactory psychometric performance.

PMID- 15561381
TI  - The annual incidence and course of neck pain in the general population: a
      population-based cohort study.
AB  - Although neck pain is a common source of disability, little is known about its
      incidence and course. We conducted a population-based cohort study of 1100
      randomly selected Saskatchewan adults to determine the annual incidence of neck
      pain and describe its course. Subjects were initially surveyed by mail in
      September 1995 and followed-up 6 and 12 months later. The age and gender
      standardized annual incidence of neck pain is 14.6% (95% confidence interval:
      11.3, 17.9). Each year, 0.6% (95% confidence interval: 0.0-1.1) of the population
      develops disabling neck pain. The annual rate of resolution of neck pain is 36.6%
      (95% confidence interval: 32.7, 40.5) and another 32.7% (95% confidence interval:
      25.5, 39.9) report improvement. Among subjects with prevalent neck pain at
      baseline, 37.3% (95% confidence interval: 33.4, 41.2) report persistent problems
      and 9.9% (95% confidence interval: 7.4, 12.5) experience an aggravation during
      follow-up. Finally, 22.8% (95% confidence interval: 16.4, 29.3) of those with
      prevalent neck pain at baseline report a recurrent episode. Women are more likely
      than men to develop neck pain (incidence rate ratio=1.67, 95% confidence interval
      1.08-2.60); more likely to suffer from persistent neck problems (incidence rate
      ratio=1.19, 95% confidence interval 1.03-1.38) and less likely to experience
      resolution (incidence rate ratio=0.75, 95% confidence interval 0.63-0.88). Neck
      pain is a disabling condition with a course marked by periods of remission and
      exacerbation. Contrary to prior belief, most individuals with neck pain do not
      experience complete resolution of their symptoms and disability.

PMID- 15561382
TI  - Laboratory pain perception and clinical pain in post-menopausal women and age
      matched men with osteoarthritis: relationship to pain coping and hormonal status.
AB  - The present study examined relationships between pain coping, hormone replacement
      therapy, and laboratory and clinical pain reports in post-menopausal women and
      age-matched men with osteoarthritis. Assessment of nociceptive flexion reflex
      threshold was followed by an assessment of electrocutaneous pain threshold and
      tolerance. Participants rated their arthritis pain using the Arthritis Impact
      Measurement Scales. To assess pain coping, participants completed measures of
      emotion-focused coping, problem-focused coping, and pain catastrophizing. Results
      indicated that women were more likely than men to report using emotion-focused
      pain strategies, and that emotion-focused coping was associated with more
      arthritic pain and lower electrocutaneous pain tolerance. Correlations between
      coping measures and pain reports revealed that catastrophizing was associated
      with greater arthritis pain and lower pain threshold and tolerance levels.
      However, catastrophizing was not related to nociceptive flexion reflex threshold,
      suggesting that the observed relationship between catastrophizing and subjective
      pain does not rely on elevated nociceptive input. A comparison of men (n=58),
      post-menopausal women receiving hormone replacement therapy (n=32), and post
      menopausal women not receiving hormone replacement therapy (n=42) revealed no
      significant group differences in arthritis pain, electrocutaneous pain threshold
      or tolerance, or nociceptive flexion reflex threshold. Thus, older adults with
      osteoarthritis do not exhibit the pattern of sex differences in response to
      experimental pain procedures observed in prior studies, possibly due to the
      development of disease-related changes in pain coping strategies. Accordingly,
      individual differences in clinical and experimental pain may be better predicted
      by pain coping than by sex or hormonal differences.

PMID- 15561383
TI  - Acceptance of the unpleasant reality of chronic pain: effects upon attention to
      pain and engagement with daily activities.
AB  - This paper investigates whether acceptance was related to less attention to pain,
      and to more engagement with daily activities. The results of two studies are
      reported. In a first cross-sectional study, 501 chronic pain patients completed
      self-report instruments on pain severity, attention to pain and acceptance. In a
      second diary study, 62 patients with chronic pain reported pain intensity,
      attention to pain and characteristics of goal-directed behaviour 8 times a day
      using an experience sampling method. Acceptance was measured using a self-report
      instrument. It was found that acceptance was related to less attention to pain
      (study 1 and study 2), more engagement with daily activities, a higher motivation
      to complete activities and a better efficacy to perform daily activities (study
      2). Results are discussed in terms of how a positive life despite pain may be
      preserved by a flexible adjustment of personal goals to current limitations and
      adversities.

PMID- 15561384
TI  - Randomised trial of long term effect of acupuncture for shoulder pain.
AB  - The objective of the study is to compare the efficacy of electro-acupuncture with
      placebo-acupuncture for the treatment of shoulder pain. This study comprised of a
      prospective, randomized, placebo controlled trial, with independent evaluator set
      in a Public primary care clinic in Spain. The participants are patients aged from
      25 to 83 years with shoulder pain. Patients were randomly allocated to two
      treatments over eight weeks, with electro-acupuncture or skin non-penetrating
      placebo-acupuncture, both able to take diclofenac if needed for intense pain.
      Primary outcome measure was the difference between groups in pain intensity
      (visual analogue scale-VAS). Secondary outcomes were differences between groups
      in pain intensity measured by Lattinen index, in range of motion (goniometer),
      functional ability (SPADI), quality of life (COOP-WONCA charts), NSAIDS intake,
      credibility (Borkoveck and Nau scale) and global satisfaction (10 points analogue
      scale). Assessments were performed before, during and three and six months after
      treatment. At six month follow-up after treatment the acupuncture group showed a
      significantly greater improvement in pain intensity compared with the control
      group [VAS mean difference 2.0 (95% CI 1.2-2.9)]. The acupuncture group had
      consistently better results in every secondary outcome measure than the control
      group. Acupuncture is an effective long-term treatment for patients with shoulder
      pain (from soft tissues lesions) in a primary care setting.

PMID- 15561385
TI  - Efficacy of two cannabis based medicinal extracts for relief of central
      neuropathic pain from brachial plexus avulsion: results of a randomised
      controlled trial.
AB  - The objective was to investigate the effectiveness of cannabis-based medicines
      for treatment of chronic pain associated with brachial plexus root avulsion. This
      condition is an excellent human model of central neuropathic pain as it
      represents an unusually homogenous group in terms of anatomical location of
      injury, pain descriptions and patient demographics. Forty-eight patients with at
      least one avulsed root and baseline pain score of four or more on an 11-point
      ordinate scale participated in a randomised, double-blind, placebo-controlled,
      three period crossover study. All patients had intractable symptoms regardless of
      current analgesic therapy. Patients entered a baseline period of 2 weeks,
      followed by three, 2-week treatment periods during each of which they received
      one of three oromucosal spray preparations. These were placebo and two whole
      plant extracts of Cannabis sativa L.: GW-1000-02 (Sativex), containing
      Delta(9)tetrahydrocannabinol (THC):cannabidiol (CBD) in an approximate 1:1 ratio
      and GW-2000-02, containing primarily THC. The primary outcome measure was the
      mean pain severity score during the last 7 days of treatment. Secondary outcome
      measures included pain related quality of life assessments. The primary outcome
      measure failed to fall by the two points defined in our hypothesis. However, both
      this measure and measures of sleep showed statistically significant improvements.
      The study medications were generally well tolerated with the majority of adverse
      events, including intoxication type reactions, being mild to moderate in severity
      and resolving spontaneously. Studies of longer duration in neuropathic pain are
      required to confirm a clinically relevant, improvement in the treatment of this
      condition.

PMID- 15561386
TI  - The association between pain and disability.
AB  - A clearer understanding of how pain intensity relates to disability could have
      important implications for pain treatment goals and definitions of treatment
      success. The objectives of this study were to determine the optimal pain
      intensity rating (0-10 scale) cutpoints for discriminating disability levels
      among individuals with work-related carpal tunnel syndrome (CTS) and low back
      (LB) injuries, whether these cutpoints differed for these conditions and for
      different disability measures, and whether the relationship between pain
      intensity and disability was linear in each injury group. Approximately 3 weeks
      after filing work injury claims, 2183 workers (1059 CTS; 1124 LB) who still had
      pain completed pain and disability measures. In the LB group, pain intensity
      rating categories of 1-4, 5-6, and 7-10 optimally discriminated disability levels
      for all four disability measures examined. In the CTS group, no pain intensity
      rating categorization scheme proved superior across all disability measures. For
      all disability measures examined, the relationship between pain intensity and
      disability level was linear in the CTS group, but nonlinear in the LB group.
      Among study participants with work-related back injuries, when pain level was 1
      4, a decrease in pain of more than 1-point corresponded to clinically meaningful
      improvement in functioning, but when pain was rated as 5-10, a 2-point decrease
      was necessary for clinically meaningful improvement in functioning. The findings
      indicate that classifying numerical pain ratings into categories corresponding to
      levels of disability may be useful in establishing treatment goals, but that
      classification schemes must be validated separately for different pain
      conditions.

PMID- 15561387
TI  - In vivo recruitment by painful stimuli of AMPA receptor subunits to the plasma
      membrane of spinal cord neurons.
AB  - The persistent increase in pain sensitivity observed after injury, known as
      hyperalgesia, depends on synaptic plasticity in the pain pathway, particularly in
      the spinal cord. Several potential mechanisms have been proposed, including post
      synaptic exocytosis of the AMPA subclass of glutamate receptors (AMPA-R), which
      is known to play a critical role in synaptic plasticity in the hippocampus. AMPA
      R trafficking has been described in spinal neurons in culture but it is unknown
      if it can also occur in spinal neurons in vivo, or if it can be induced by
      natural painful stimulation. Here we have induced referred mechanical
      hyperalgesia in vivo by intracolonic instillation of capsaicin in mice and have
      observed a recruitment of GluR1 AMPA-R subunits to neuronal plasma membranes in
      the lumbar spinal cord. Intracolonic capsaicin induced a rapid (10 min) increase
      in GluR1, but not GluR2/3 in the synaptosomal membrane fraction which lasted at
      least 3 h and a decrease in GluR1 subunit in the cytosolic fraction. Capsaicin
      treatment also provoked CaMKII activation and pre-treatment with a specific
      CaMKII inhibitor prevented the GluR1 trafficking. Brefeldin-A, an antibiotic that
      inhibits exocytosis of proteins, not only prevented GluR1 trafficking to the
      membrane but also inhibited referred hyperalgesia in capsaicin-treated mice. Our
      results show that delivery of GluR1 AMPA receptor subunits to the cell membrane
      through a CaMKII activity-dependent exocytotic regulated pathway contributes to
      the development of hyperalgesia after a painful stimulus. We conclude that AMPA-R
      trafficking contributes to the synaptic strengthening induced in the pain pathway
      by natural stimulation.

PMID- 15561388
TI  - Increase in muscle nociceptive substances and anaerobic metabolism in patients
      with trapezius myalgia: microdialysis in rest and during exercise.
AB  - Local metabolic changes are suggested to be involved in muscle pain development
      in humans. Nineteen women with chronic work-related trapezius myalgia (TM) and 20
      healthy female controls (CON) were studied during baseline rest, 20 min
      repetitive low-force exercise, and 120 min recovery. Interstitial serotonin (5
      HT), glutamate, lactate, pyruvate, and blood flow were determined by
      microdialysis in the trapezius muscle. Baseline pressure pain threshold (PPT) was
      lower (143+/-18 (TM) vs. 269+/-17 (CON)kPa) (mean+/-SEM), pain intensity (visual
      analogue scale, VAS) higher (33+/-5 vs. 2+/-1mm), muscle 5-HT higher (22.9+/-6.7
      vs. 3.8+/-1.3 nmol/l), and glutamate higher (47+/-3 vs. 36+/-4 micromol/l) in TM
      than in CON (all P<0.05), whereas muscle blood flow was similar in groups.
      Furthermore, muscle pyruvate was higher (180+/-15 vs. 135+/-12 micromol/l) and
      lactate higher (4.4+/-0.3 vs. 3.1+/-0.3 mmol/l) in TM than in CON (P<0.001). In
      response to exercise, VAS and glutamate increased in both TM and CON (all
      P<0.05). In TM only, lactate and pyruvate increased significantly (P<0.02),
      whereas blood flow increased to similar levels in both groups. During the initial
      20 min recovery period, blood flow remained increased in TM (P<0.005) whereas it
      decreased to baseline levels in CON. In conclusion, patients with chronic work
      related TM have increased levels of muscle 5-HT and glutamate that were
      correlated to pain intensity (r=0.55, P<0.001) and PPT (r=-0.47, P<0.001),
      respectively. In addition, TM was associated with increased anaerobic metabolism,
      whereas a normal rise in blood flow was seen with exercise. These findings
      indicate that peripheral nociceptive processes are active in work-related TM.

PMID- 15561389
TI  - Electronic diary assessment of pain-related fear, attention to pain, and pain
      intensity in chronic low back pain patients.
AB  - The present study investigated the relationships between pain-related fear,
      attention to pain, and pain intensity in daily life in patients with chronic low
      back pain. An experience sampling methodology was used in which electronic diary
      data were collected by means of palmtop computers from 40 chronic low back pain
      patients who were followed for one week. Attention to pain was hypothesized to
      mediate the relation between pain-related fear and pain intensity. Further, pain
      related fear as a trait characteristic was expected to moderate the relation
      between attention to pain and pain intensity. Multi-level analysis was used for
      all analyses. Although the tested mediation models yielded statistically
      significant mediation effects, the sizes of these effects were relatively small
      and clinically irrelevant. Instead, results suggested that pain-related fear and
      attention to pain independently predicted pain intensity. No evidence for
      moderation of the relation between attention to pain and pain intensity by pain
      related fear as a trait characteristic was found. Implications of the results
      from this study are discussed and suggestions for future research are provided.

PMID- 15561390
TI  - Fear-avoidance beliefs and distress in relation to disability in acute and
      chronic low back pain.
AB  - Patients with chronic low back pain (LBP) frequently demonstrate high scores for
      fear-avoidance beliefs and distress. We need better knowledge about fear
      avoidance beliefs and distress in early stages of LBP. The objectives of this
      study were to compare the level of fear-avoidance beliefs and distress in
      patients with acute LBP to patients with chronic LBP, and to assess the
      relationship of fear-avoidance beliefs and distress to disability in acute and
      chronic LBP. Two different back pain groups including 123 patients with acute and
      233 patients with chronic LBP were studied. Main outcome measures were Oswestry
      Disability Index and work loss. The scores for fear-avoidance beliefs and
      distress in patients with acute LBP were significantly lower than among patients
      with chronic LBP. The results of the multivariate regression analyses, adjusting
      for sociodemographic, pain and clinical variables, demonstrated that whereas fear
      avoidance beliefs for physical activity and distress were significantly
      associated with the Oswestry Disability Index, fear-avoidance beliefs for work
      and distress were significantly associated with work loss. The associations
      showed the same pattern in acute and chronic LBP. In addition, several of the
      pain and clinical variables were significantly associated with the Oswestry
      Disability Index and fingertip-floor distance was associated with work loss. In
      conclusion, fear-avoidance beliefs and distress influence pain-related disability
      both in early acute and long-term chronic LBP. The results replicate previous
      reports on the association between pain experience, fear-avoidance beliefs,
      distress, and disability in chronic LBP, and extend the findings to patients at
      an early stage of acute LBP.

PMID- 15561391
TI  - Effects of diffuse noxious inhibitory controls on temporal summation of the RIII
      reflex in humans.
AB  - The aim of this study was to investigate the effects of diffuse noxious
      inhibitory controls (DNICs) on the temporal summation of the nociceptive flexion
      reflex (RIII reflex) in humans. Recordings were obtained from 36 healthy adults
      (16 M, 20 F), and the area and temporal summation threshold (TST) of the RIII
      reflex were measured. The subjective intensity of the painful sensation was rated
      on an 11-point visual analogue scale (VAS). Neurophysiological and VAS
      measurements were recorded after activation of DNICs by means of the cold pressor
      test (CPT), which involved immersing the hand in cold water (2-4 degrees C). A
      slight significant lower TST was found in the females versus the males. In all
      the subjects, the CPT induced a significant TST increase and RIII area reduction
      compared with the control session. The VAS results paralleled those of the RIII
      reflex area and TST. During the CPT, a significant difference in the percentage
      TST increase emerged between females and males, being lower in the former.
      Similarly, we found a significantly lower percentage reduction of the RIII area
      in women than in men during the CPT. To summarize, activation of DNICs through
      the CPT significantly increased the TST of the RIII reflex in healthy subjects.
      This inhibitory effect was gender-specific. Whereas other findings are based on
      psychophysical evaluations, the results of this experimental study provide an
      objective neurophysiological demonstration that DNICs attenuate temporal
      summation in humans and confirm the presence of significant differences in pain
      modulation mechanisms between men and women.

PMID- 15561392
TI  - The effects of acute and chronic restraint stress on activation of ERK in the
      rostral ventromedial medulla and locus coeruleus.
AB  - Extracellular signal-regulated kinase (ERK) is a key molecule in numerous
      cellular and physiological processes in the CNS. Exposure to stressors causes
      substantial effects on the perception and response to pain. The rostral
      ventromedial medulla (RVM) and the locus coeruleus (LC) play crucial roles in
      descending pain modulation system. In the present study, the activation of ERK in
      the RVM and the LC in rats following acute and chronic restraint stress was
      examined in order to characterize the mechanisms underlying stress induced
      analgesic and hyperalgesic responses. Rats were stressed by restraint 6h daily
      for 3 weeks. The acute and chronic restraint stresses produced analgesic and
      hyperalgesic reactions, respectively, to thermal stimuli applied to the tail. The
      phospho-ERK-immunoreactive (p-ERK-IR) neurons were observed in the nucleus raphe
      magnus (NRM), nucleus reticularis gigantocellularis pars alpha (GiA) and LC. In
      the RVM, the number of p-ERK-IR neurons per section in the 3-week restraint rats
      (14.3+/-1.2) was significantly higher than that in the control rats (8.9+/-0.7)
      [P<0.01]. About 75% of p-ERK-IR neurons in the RVM in the 3-week restraint rats
      were serotonergic neurons. Protein levels of tryptophan hydroxylase were
      significantly increased in the RVM region in the 3-week restraint rats. On the
      other hand, the chronic restraint stress significantly decreased p-ERK-IR in the
      LC [P<0.05]. These findings suggest that chronic restraint stress-induced
      activation of ERK in the RVM and the suppression in the LC may be involved in the
      modulation of the pain threshold by chronic stress.

PMID- 15561393
TI  - Opioids in chronic non-cancer pain: systematic review of efficacy and safety.
AB  - Opioids are used increasingly for chronic non-cancer pain. Controversy exists
      about their effectiveness and safety with long-term use. We analysed available
      randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and
      safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994)
      and Medline, EMBASE and the Cochrane Library were searched until September 2003.
      Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo
      in chronic non-cancer pain. Double-blind studies reporting on pain intensity
      outcomes using validated pain scales were included. Fifteen randomised placebo
      controlled trials were included. Four investigations with 120 patients studied
      intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids
      with placebo for four days to eight weeks. Six of the 15 included trials had an
      open label follow-up of 6-24 months. The mean decrease in pain intensity in most
      studies was at least 30% with opioids and was comparable in neuropathic and
      musculoskeletal pain. About 80% of patients experienced at least one adverse
      event, with constipation (41%), nausea (32%) and somnolence (29%) being most
      common. Only 44% of 388 patients on open label treatments were still on opioids
      after therapy for between 7 and 24 months. The short-term efficacy of opioids was
      good in both neuropathic and musculoskeletal pain conditions. However, only a
      minority of patients in these studies went on to long-term management with
      opioids. The small number of selected patients and the short follow-ups do not
      allow conclusions concerning problems such as tolerance and addiction.

PMID- 15561394
TI  - The effectiveness of physiotherapy and manipulation in patients with tension-type
      headache: a systematic review.
AB  - The study design is a systematic review of randomised clinical trials (RCTs). The
      objectives of the present study are to assess the effectiveness of physiotherapy
      and (spinal) manipulation in patients with tension-type headache (TTH). No
      systematic review exists concerning the effectiveness of physiotherapy and
      (spinal) manipulation primarily focussing on TTH. Literature was searched using a
      computerised search of MEDLINE, EMBASE and the Cochrane library. Only RCTs
      including physiotherapy and/or (spinal) manipulation used in the treatment of TTH
      in adults were selected. Two reviewers independently assessed the methodological
      quality of the RCTs using the Delphi-list. A study was considered of high quality
      if it satisfied at least six points on the methodological quality list. Twelve
      publications met the inclusion criteria, including three dual or overlapping
      publications resulting in eight studies included. These studies showed a large
      variety of interventions, such as chiropractic spinal manipulation, connective
      tissue manipulation or physiotherapy. Only two studies were considered to be of
      high quality, but showed inconsistent results. Because of clinical heterogeneity
      and poor methodological quality in many studies, it appeared to be not possible
      to draw valid conclusions. Therefore, we conclude that there is insufficient
      evidence to either support or refute the effectiveness of physiotherapy and
      (spinal) manipulation in patients with TTH.

PMID- 15561395
TI  - Management of occupational back injuries: differences among African Americans and
      Caucasians.
AB  - This study examined differences in the case management of occupational low back
      injuries in a large, racially diverse population of Workers' Compensation
      claimants in Missouri. Participants were African Americans (N=580) and non
      Hispanic whites (N=892) who had filed occupational injury claims that were
      settled over an 18-month period. Telephone interview data were gathered regarding
      diagnoses, legal representation, demographics, and socioeconomic status. The
      Missouri Division of Workers' Compensation also provided information on medical
      and temporary disability expenditures, claim duration, final disability ratings,
      and settlement awards. Simultaneous-entry, hierarchical multiple and logistic
      regression analyses showed significant and substantial effects for injury-related
      variables, socioeconomic status, and race across all Workers' Compensation
      variables. Differences remained for both injury and African Americans and lower
      socioeconomic status workers after controlling for injury, and for African
      Americans after controlling for both injury and socioeconomic status. Because
      Workers' Compensation mandates equal access to treatment and disability
      reimbursement for all injured workers, the differences observed in this study may
      reflect sociocultural biases in disability management among healthcare providers.

PMID- 15561396
TI  - Social networks and pain interference with daily activities in middle and old
      age.
AB  - Social networks have emerged as important in the development and progression of
      disability in aging cohorts. We have previously reported that pain that
      interferes with daily activities is common and increases incrementally from
      middle age into later life. The current study has investigated whether pain
      interference in this age group is related to social network characteristics. 5215
      community-dwelling adults aged 50 years and over participating in the North
      Staffordshire Osteoarthritis Project (NorStOP) and identified as currently
      experiencing pain formed the sample for the present analysis. Questions on pain
      related interference and the number and frequency of contact with children, close
      relatives, close friends, and confidant were included in the baseline postal
      questionnaire. The number and frequency of contact for most social ties declined
      with age. Being widowed (Age-adjusted OR: 1.30; 95%CI: 1.10, 1.54), the absence
      of close friends (2.07; 1.64, 2.63), and the absence of close relatives for women
      (2.24; 1.66, 3.04) were associated with increased likelihood of pain interference
      with daily activities. The absence of children was linked to lower levels of pain
      interference (0.76; 0.64, 0.91). The associations with close friends and children
      were reduced but remained significant after adjusting for sociodemographic
      factors. The association with close friends became non-significant after
      adjusting for depression suggesting this may form part of the pathway linking
      close friends networks and pain interference. Pain-related interference shows
      similar associations with social networks as all-cause disability and may benefit
      similarly from a public health perspective.

PMID- 15561397
TI  - Spinal cord stimulation in a patient with persistent oesophageal pain.
AB  - This study describes a man with a long history of oesophageal pain that led to
      inability to swallow food and drink. Over a period of 8 years, he had multiple
      oesophageal operations that were unsuccessful. He presented, to the pain
      management team, with persistent oesophageal pain and required jejunostomy tube
      feeding to maintain nutrition. Conservative pain management strategies failed.
      Spinal cord stimulation (SCS) was suggested, and after counseling, an electrode
      was placed in the high thoracic region. Stimulation covered the area of the chest
      pain. He achieved immediate reduced pain on swallowing water. A permanent system
      was implanted. In this case, SCS resulted in a significant improvement in pain on
      swallowing liquids. The patient can now also eat certain foods occasionally and
      enjoy the social aspect of eating; this was impossible previously. He feels that
      SCS has been worthwhile. The authors discuss the rationale for this treatment.
      The decision was based on the use of SCS for refractory angina, and the idea that
      the neural mechanisms that generate both these pain states may be similar.

PMID- 15561398
TI  - Comment on: Familial aggregation of depression in fibromyalgia: a community-based
      test of alternative hypotheses, Raphael et al., Pain 110 (2004) 449-460.

PMID- 15561400
TI  - Letter to the editor regarding He et al., "Effect of acupuncture treatment on
      chronic neck and shoulder pain in sedentary female workers: a 6-month and 3-year
      follow-up study" (Pain 109:299-307).

PMID- 15561402
TI  - Towards a molecular understanding of water homeostasis in the brain.

PMID- 15561403
TI  - Water homeostasis in the brain: basic concepts.
AB  - The mammalian CNS is separated from the blood by tight junctions, collectively
      termed the blood-brain barrier (BBB). This imposes unique features of solvent and
      water movement into and out of the CNS. The basic equations for water fluxes
      driven by osmotic gradients are presented. The anatomy of the BBB and the
      physiology of the transport processes for cerebrospinal fluid production,
      extracellular fluid production and intercellular water and solute transport are
      then described. A quantitative analysis of the need for aquaporin-based water
      movements to accompany the known rates of CSF production is also presented.
      Finally, the mechanisms and roles of cellular and vasogenic edema in the CNS,
      especially in relation to aquaporins, are described.

PMID- 15561404
TI  - Extrasynaptic volume transmission and diffusion parameters of the extracellular
      space.
AB  - Extrasynaptic communication between neurons or neurons and glia is mediated by
      the diffusion of neuroactive substances in the volume of the extracellular space
      (ECS). The size and irregular geometry of the diffusion channels in the ECS
      substantially differ not only around individual cells but also in different CNS
      regions and thus affect and direct the movement of various neuroactive substances
      in the ECS. Diffusion in the CNS is therefore not only inhomogeneous, but often
      also anisotropic. The diffusion parameters in adult mammals (including humans),
      ECS volume fraction alpha (alpha=ECS volume/total tissue volume) and tortuosity
      lambda (lambda(2)=free/apparent diffusion coefficient), are typically 0.20-0.25
      and 1.5-1.6, respectively, and as such hinder the diffusion of neuroactive
      substances and water. These diffusion parameters modulate neuronal signaling,
      neuron-glia communication and extrasynaptic "volume" transmission. A significant
      decrease in ECS volume fraction and an increase in diffusion barriers
      (tortuosity) occur during neuronal activity and pathological states. The changes
      are often related to cell swelling, cell loss, astrogliosis, the rearrangement of
      neuronal and astrocytic processes and changes in the extracellular matrix. They
      are also altered during physiological states such as development, lactation and
      aging. Plastic changes in ECS volume, tortuosity and anisotropy significantly
      affect neuron-glia communication, the spatial relation of glial processes toward
      synapses, glutamate or GABA "spillover" and synaptic crosstalk. The various
      changes in tissue diffusivity occurring during many pathological states are
      important for diagnosis, drug delivery and treatment.

PMID- 15561405
TI  - The neurobiology of glia in the context of water and ion homeostasis.
AB  - Astrocytes are highly complex cells that respond to a variety of external
      stimulations. One of the chief functions of astrocytes is to optimize the
      interstitial space for synaptic transmission by tight control of water and ionic
      homeostasis. Several lines of work have, over the past decade, expanded the role
      of astrocytes and it is now clear that astrocytes are active participants in the
      tri-partite synapse and modulate synaptic activity in hippocampus, cortex, and
      hypothalamus. Thus, the emerging concept of astrocytes includes both supportive
      functions as well as active modulation of neuronal output. Glutamate plays a
      central role in astrocytic-neuronal interactions. This excitatory amino acid is
      cleared from the neuronal synapses by astrocytes via glutamate transporters, and
      is converted into glutamine, which is released and in turn taken up by neurons.
      Furthermore, metabotropic glutamate receptor activation on astrocytes triggers
      via increases in cytosolic Ca(2+) a variety of responses. For example, calcium
      dependent glutamate release from the astrocytes modulates the activity of both
      excitatory and inhibitory synapses. In vivo studies have identified the
      astrocytic end-foot processes enveloping the vessel walls as the center for
      astrocytic Ca(2+) signaling and it is possible that Ca(2+) signaling events in
      the cellular component of the blood-brain barrier are instrumental in modulation
      of local blood flow as well as substrate transport. The hormonal regulation of
      water and ionic homeostasis is achieved by the opposing effects of vasopressin
      and atrial natriuretic peptide on astroglial water and chloride uptake. In
      conjuncture, the brain appears to have a distinct astrocytic perivascular system,
      involving several potassium channels as well as aquaporin 4, a membrane water
      channel, which has been localized to astrocytic endfeet and mediate water fluxes
      within the brain. The multitask functions of astrocytes are essential for higher
      brain function. One of the major challenges for future studies is to link
      receptor-mediated signaling events in astrocytes to their roles in metabolism,
      ion, and water homeostasis.

PMID- 15561406
TI  - From finch to fish to man: role of aquaporins in body fluid and brain water
      regulation.
AB  - Charles Darwin, in his Origin of the Species, noted that different species of
      finches on the Galapagos Islands had adapted their beak size based on where they
      sought their food. Homer Smith, in his book From Fish to Philosopher, discussed
      the evolution of the nephron from a single conduit in salt water vertebrates, to
      nephrons with large glomerular capillaries and proximal and distal tubules in
      fresh water vertebrates, to smaller glomerular capillaries in amphibians, to
      nephrons with loops of Henle to allow for urinary concentration and dilution in
      mammals. The kidney with its million nephrons has emerged as the vital organ for
      regulating body fluid composition and volume. With the recent discovery of
      aquaporin water channels, our understanding of volume regulation has been greatly
      enhanced. This article reviews current knowledge regarding: 1) the unifying
      hypothesis of body fluid volume regulation; 2) brain aquaporins and their role in
      pathophysiologic states; and 3) function and regulation of renal aquaporins in
      the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

PMID- 15561407
TI  - Aquaporin-4 in the central nervous system: cellular and subcellular distribution
      and coexpression with KIR4.1.
AB  - Aquaporin-4 (AQP4) is the predominant water channel in the neuropil of the
      central nervous system. It is expressed primarily in astrocytes, but also occurs
      in ependymocytes and endothelial cells. A striking feature of AQP4 expression is
      its polarized distribution in brain astrocytes and retinal Muller cells. Thus,
      immunogold analyses have revealed an enrichment of AQP4 in endfeet membranes in
      contact with brain microvessels or subarachnoidal space and a low but significant
      concentration in non-endfeet membranes, including those astrocyte membranes that
      ensheath glutamate synapses. The subcellular compartmentation of AQP4 mimics that
      of the potassium channel Kir4.1, which is implicated in spatial buffering of
      K(+). We propose that AQP4 works in concert with Kir4.1 and the electrogenic
      bicarbonate transporter NBC and that water flux through AQP4 contributes to the
      activity dependent volume changes of the extracellular space. Such volume changes
      are important as they affect the extracellular solute concentrations and
      electrical fields, and hence neuronal excitability. We conclude that AQP4
      mediated water flux represents an integral element of brain volume and ion
      homeostasis.

PMID- 15561409
TI  - The role of aquaporin-4 in the blood-brain barrier development and integrity:
      studies in animal and cell culture models.
AB  - Aquaporin-4 (AQP4) is the major water channel expressed in brain perivascular
      astrocyte processes. Although the role of AQP4 in brain edema has been
      extensively investigated, little information exists regarding its functional role
      at the blood-brain barrier (BBB). The purpose of this work is to integrate
      previous and recent data regarding AQP4 expression during BBB formation and
      depending on BBB integrity, using several experimental models. Results from
      studies on the chick optic tectum, a well-established model of BBB development,
      and the effect of lipopolysaccharide on the BBB integrity and on perivascular
      AQP4 expression have been analyzed and discussed. Moreover, data on the BBB
      structure and AQP4 expression in murine models of Duchenne muscular dystrophy are
      reviewed. In particular, published results obtained from mdx(3cv) mice have been
      analyzed together with new data obtained from mdx mice in which all the
      dystrophin isoforms including DP71 are strongly reduced. Finally, the role of the
      endothelial component on AQP4 cellular expression and distribution has been
      investigated using rat primary astrocytes and brain capillary endothelial cell co
      cultures as an in vitro model of BBB.

PMID- 15561408
TI  - Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with
      models of AQP4 lattice assembly.
AB  - Each day, approximately 0.5-0.9 l of water diffuses through (primarily) aquaporin
      1 (AQP1) channels in the human choroid plexus, into the cerebrospinal fluid of
      the brain ventricles and spinal cord central canal, through the ependymal cell
      lining, and into the parenchyma of the CNS. Additional water is also derived from
      metabolism of glucose within the CNS parenchyma. To maintain osmotic homeostasis,
      an equivalent amount of water exits the CNS parenchyma by diffusion into
      interstitial capillaries and into the subarachnoid space that surrounds the brain
      and spinal cord. Most of that efflux is through AQP4 water channels concentrated
      in astrocyte endfeet that surround capillaries and form the glia limitans. This
      report extends the ultrastructural and immunocytochemical characterizations of
      the crystalline aggregates of intramembrane proteins that comprise the AQP4
      "square arrays" of astrocyte and ependymocyte plasma membranes. We elaborate on
      recent demonstrations in Chinese hamster ovary cells of the effects on AQP4 array
      assembly resulting from separate vs. combined expression of M1 and M23 AQP4,
      which are two alternatively spliced variants of the AQP4 gene. Using improved
      shadowing methods, we demonstrate sub-molecular cross-bridges that link the
      constituent intramembrane particles (IMPs) into regular square lattices of AQP4
      arrays. We show that the AQP4 core particle is 4.5 nm in diameter, which appears
      to be too small to accommodate four monomeric proteins in a tetrameric IMP.
      Several structural models are considered that incorporate freeze-fracture data
      for submolecular "cross-bridges" linking IMPs into the classical square lattices
      that characterize, in particular, naturally occurring AQP4.

PMID- 15561410
TI  - Regulation of brain aquaporins.
AB  - Emerging evidence suggests that brain aquaporins (AQP) play important roles for
      the dynamic regulation of brain water homeostasis and for the regulation of
      cerebrospinal fluid production. This review deals with the short- and long-term
      regulation of AQP4 and AQP9, both expressed in astrocytes, and of AQP1, expressed
      in the choroid plexus. AQP1 and 4 have in other cell types been shown to be
      regulated by phosphorylation. Phosphorylation affects the gating of AQP4 and the
      trafficking and insertion into membrane of AQP1. Mercury inhibits the water
      permeability of AQP1 and AQP9, but not AQP4. The permeability of AQP4 is
      increased by lead. AQP4 is also regulated by protein-protein interaction. The
      assembly between AQP4 and syntrophin is required for the proper localization of
      AQP4 in the astrocyte plasma membrane that faces capillaries. There is evidence
      from studies on peripheral tissues that steroid hormones regulate the expression
      of AQP1, AQP4 and AQP9. There is also evidence that the expression of AQP1 can be
      regulated by ubiquitination, and that osmolality can regulate the expression of
      AQP1, AQP4 and AQP9. Further insight into the mechanisms by which brain AQPs are
      regulated will be of utmost clinical importance, since perturbed water flow via
      brain AQPs has been implicated in many neurological diseases and since, in brain
      edema, water flow via AQP4 may have a harmful effect.

PMID- 15561411
TI  - Molecular mechanisms of cerebrospinal fluid production.
AB  - The epithelial cells of the choroid plexuses secrete cerebrospinal fluid (CSF),
      by a process which involves the transport of Na(+), Cl(-) and HCO(3)(-) from the
      blood to the ventricles of the brain. The unidirectional transport of ions is
      achieved due to the polarity of the epithelium, i.e. the ion transport proteins
      in the blood-facing (basolateral) membrane are different to those in the
      ventricular (apical) membrane. The movement of ions creates an osmotic gradient
      which drives the secretion of H(2)O. A variety of methods (e.g. isotope flux
      studies, electrophysiological, RT-PCR, in situ hybridization and
      immunocytochemistry) have been used to determine the expression of ion
      transporters and channels in the choroid plexus epithelium. Most of these
      transporters have now been localized to specific membranes. For example, Na(+)
      K(+)ATPase, K(+) channels and Na(+)-2Cl(-)-K(+) cotransporters are expressed in
      the apical membrane. By contrast the basolateral membrane contains Cl(-)- HCO(3)
      exchangers, a variety of Na(+) coupled HCO(3)(-) transporters and K(+)-Cl(-)
      cotransporters. Aquaporin 1 mediates water transport at the apical membrane, but
      the route across the basolateral membrane is unknown. A model of CSF secretion by
      the mammalian choroid plexus is proposed which accommodates these proteins. The
      model also explains the mechanisms by which K(+) is transported from the CSF to
      the blood.

PMID- 15561412
TI  - Distribution and possible roles of aquaporin 9 in the brain.
AB  - Aquaporin 9 (AQP9) is a member of the aquaporin channel family involved in water
      flux through plasma membranes and exhibits the distinct feature of being also
      permeable to monocarboxylates, such as lactate, and various solutes, including
      glycerol, carbamides, purines, pyrimidines, and urea. AQP9 is constitutively
      expressed at high levels in the liver. In the brain under physiological
      conditions, AQP9 was first observed in tanycytes, and then in astrocytes. Only
      recently, its expression was also shown in neurons. Neurons expressing AQP9 are
      catecholaminergic and glucose sensitive. The expression of neuronal AQP9 can be
      negatively regulated by insulin and in diabetic animals an increase in AQP9
      expression is observed in the catecholaminergic nuclei of the hindbrain, similar
      to the regulation of AQP9 by insulin in the liver. Furthermore, after transient
      brain ischemia, AQP9 expression is increased in astrocytes and its regulation may
      implicate the MAP-kinase pathways stimulated in such pathological conditions.
      Despite these new data, the exact role of AQP9 in the brain is still unclear.
      However, we may hypothesize that AQP9 is implicated in brain energy metabolism,
      as a neutral solute channel. AQP9 could facilitate the diffusion of lactate from
      the astrocyte to the neuron. In glucose sensitive neurons, diffusion of lactate
      and glycerol could stimulate these neurons in a similar manner to glucose and
      could regulate the energy balance. In pathological conditions, induction of AQP9
      in astrocytes could participate in the clearance of excess lactate in the
      extracellular space. These hypotheses concerning the function of brain AQP9 are
      still speculative and open new areas of investigation.

PMID- 15561413
TI  - New insights into water transport and edema in the central nervous system from
      phenotype analysis of aquaporin-4 null mice.
AB  - Aquaporin-4 (AQP4) is the major water channel in the CNS. Its expression at fluid
      tissue barriers (blood-brain and brain-cerebrospinal fluid barriers) throughout
      the brain and spinal cord suggests a role in water transport under normal and
      pathological conditions. Phenotype studies of transgenic mice lacking AQP4 have
      provided evidence for a role of AQP4 in cerebral water balance and neural signal
      transduction. Primary cultures of astrocytes from AQP4-null mice have greatly
      reduced osmotic water permeability compared with wild-type astrocytes, indicating
      that AQP4 is the principal water channel in these cells. AQP4-null mice have
      reduced brain swelling and improved neurological outcome following water
      intoxication and focal cerebral ischemia, establishing a role of AQP4 in the
      development of cytotoxic (cellular) cerebral edema. In contrast, brain swelling
      and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid
      leak) edema caused by freeze-injury and brain tumor, probably due to impaired
      AQP4-dependent brain water clearance. AQP4-null mice also have markedly reduced
      acoustic brainstem response potentials and significantly increased seizure
      threshold in response to chemical convulsants, implicating AQP4 in modulation of
      neural signal transduction. Pharmacological modulation of AQP4 function may thus
      provide a novel therapeutic strategy for the treatment of stroke, tumor
      associated edema, epilepsy, traumatic brain injury, and other disorders of the
      CNS associated with altered brain water balance.

PMID- 15561414
TI  - Studies of mdx mice.
AB  - Cerebral water accumulation-clinically denoted as brain edema-is a potentially
      life threatening complication of almost every intracranial neuropathological
      state. The molecular membrane water channel aquaporin-4 (AQP4) has been shown to
      be present at the blood-brain barrier (BBB) where it plays pivotal role in the
      transport of water between the tissue water compartments of the brain.
      Accumulating evidence indicates that the blockade of AQP4 function at the BBB
      would be a new therapeutic approach to the treatment and prevention of brain
      swelling. The cytoskeletal protein dystrophin has been shown to be involved in
      the maintenance of the polarized expression of AQP4 at the BBB. In order to
      further elucidate the mechanisms responsible for the highly polarized AQP4
      expression, we studied brain tissue water accumulation during induction of brain
      edema in dystrophin-null transgenic mice (mdx-bgeo) and control mice.
      Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null
      brains revealed a dramatic reduction of AQP4 in astroglial end-feet surrounding
      capillaries (BBB) and at the glia limitans (cerebrospinal fluid-brain interface).
      The AQP4 protein is mislocalized, because immunoblotting showed that the total
      AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection
      of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water
      compartments were assessed by diffusion-weighted MRI (DWI) with determination of
      the apparent diffusion coefficient (ADC). In dystrophin-null mice and control
      mice, ADC gradually decreased by 5-6% from baseline levels during the first 35
      min, indicating the initial phase of intracellular water accumulation is similar
      in the two groups. At this point, the control mice sustained an abrupt, rapid
      decline in ADC to 58%+/-2.2% of the baseline at 52.5 min, and all of the animals
      were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained
      a similar decline in ADC to 55%+/-3.4% at 66.5 min, when all of the mice were
      dead. These results demonstrate that dystrophin is necessary for polarized
      distribution of AQP4 protein in brain where facilitated movements of water occur
      across the BBB and cerebrospinal fluid-brain interface. Moreover, these results
      predict that interference with the subcellular localization of AQP4 may have
      therapeutic potential for delaying the onset of impending brain edema.

PMID- 15561415
TI  - Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the
      physiology and pathophysiology of water transport.
AB  - Astrocytes show an enrichment of aquaporin-4 (AQP4) in those parts of the plasma
      membrane that are apposed to pial or perivascular basal laminae. This observation
      begged the following questions: 1, What are the molecular mechanisms that are
      responsible for the site specific anchoring of AQP4? 2, What are the
      physiological and pathophysiological roles of the AQP4 pools at these specialized
      membrane domains? Recent studies suggest that the site specific anchoring depends
      on the dystrophin complex. Further, alpha-syntrophin (a member of the dystrophin
      complex) is required to maintain a polarized expression of AQP4 in the
      perivascular membranes. Hence transgenic mice deficient in alpha-syntrophin
      provided a model where the perivascular pool of AQP4 could be removed for
      assessment of its functional roles. Data suggest that the perivascular pool of
      AQP4 plays a role in edema formation and that this pool (through its serial
      coupling with the AQP4 pools in other astrocyte membranes) is involved in K(+)
      siphoning. In the cerebral cortex, the astrocyte membrane domain contacting the
      pial basal lamina differs from the perivascular membrane domain in regard to the
      mechanisms for AQP anchoring. Thus deletion of alpha-syntrophin causes only a 50%
      loss of AQP4 from the former membrane (compared with a 90% loss in the latter),
      pointing to the existence of additional anchoring proteins. We will also discuss
      the subcellular distribution and anchoring of AQP4 in the other cell types that
      express this protein: endothelial cells, ependymal cells, and the specialized
      astrocytes of the osmosensitive organs.

PMID- 15561416
TI  - Molecular mechanisms of brain tumor edema.
AB  - Despite their diverse histological types, most brain tumours cause brain oedema,
      which is a significant cause of patient morbidity and mortality. Brain tumour
      oedema occurs when plasma-like fluid enters the brain extracellular space through
      impaired capillary endothelial tight junctions in tumours. Under-expression of
      the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular
      abnormalities responsible for the increased permeability of tumour endothelial
      tight junctions. Recent evidence suggests that the membrane water channel protein
      aquaporin-4 (AQP4) also plays a role in brain tumour oedema. AQP4-deficient mice
      show remarkably altered brain water balance after various insults, including
      brain tumour implantation. AQP4 expression is strongly upregulated around
      malignant human brain tumours in association with reduced extracellular volume,
      which may restrict the flow of extracellular fluid from the tumour bed into the
      brain parenchyma. Elimination of excess fluid leaking into brain parenchyma
      requires passage across three AQP4-rich barriers: a) the glia limitans externa,
      b) the glia limitans interna/ependyma, and c) the blood-brain barrier. Modulation
      of the expression and/or function of endothelial tight junction proteins and
      aquaporins may provide novel therapeutic options for reducing brain tumour
      oedema.

PMID- 15561417
TI  - Edema and brain trauma.
AB  - Brain edema leading to an expansion of brain volume has a crucial impact on
      morbidity and mortality following traumatic brain injury (TBI) as it increases
      intracranial pressure, impairs cerebral perfusion and oxygenation, and
      contributes to additional ischemic injuries. Classically, two major types of
      traumatic brain edema exist: "vasogenic" due to blood-brain barrier (BBB)
      disruption resulting in extracellular water accumulation and "cytotoxic/cellular"
      due to sustained intracellular water collection. A third type, "osmotic" brain
      edema is caused by osmotic imbalances between blood and tissue. Rarely after TBI
      do we encounter a "hydrocephalic edema/interstitial" brain edema related to an
      obstruction of cerebrospinal fluid outflow. Following TBI, various mediators are
      released which enhance vasogenic and/or cytotoxic brain edema. These include
      glutamate, lactate, H(+), K(+), Ca(2+), nitric oxide, arachidonic acid and its
      metabolites, free oxygen radicals, histamine, and kinins. Thus, avoiding cerebral
      anaerobic metabolism and acidosis is beneficial to control lactate and H(+), but
      no compound inhibiting mediators/mediator channels showed beneficial results in
      conducted clinical trials, despite successful experimental studies. Hence, anti
      edematous therapy in TBI patients is still symptomatic and rather non-specific
      (e.g. mannitol infusion, controlled hyperventilation). For many years, vasogenic
      brain edema was accepted as the prevalent edema type following TBI. The
      development of mechanical TBI models ("weight drop," "fluid percussion injury,"
      and "controlled cortical impact injury") and the use of magnetic resonance
      imaging, however, revealed that "cytotoxic" edema is of decisive
      pathophysiological importance following TBI as it develops early and persists
      while BBB integrity is gradually restored. These findings suggest that cytotoxic
      and vasogenic brain edema are two entities which can be targeted simultaneously
      or according to their temporal prevalence.

PMID- 15561418
TI  - Water transport in the brain: role of cotransporters.
AB  - It is generally accepted that cotransporters transport water in addition to their
      normal substrates, although the precise mechanism is debated; both active and
      passive modes of transport have been suggested. The magnitude of the water flux
      mediated by cotransporters may well be significant: both the number of
      cotransporters per cell and the unit water permeability are high. For example,
      the Na(+)-glutamate cotransporter (EAAT1) has a unit water permeability one tenth
      of that of aquaporin (AQP) 1. Cotransporters are widely distributed in the brain
      and participate in several vital functions: inorganic ions are transported by
      K(+)-Cl(-) and Na(+)-K(+)-Cl(-) cotransporters, neurotransmitters are reabsorbed
      from the synaptic cleft by Na(+)-dependent cotransporters located on glial cells
      and neurons, and metabolites such as lactate are removed from the extracellular
      space by means of H(+)-lactate cotransporters. We have previously determined
      water transport capacities for these cotransporters in model systems (Xenopus
      oocytes, cell cultures, and in vitro preparations), and will discuss their role
      in water homeostasis of the astroglial cell under both normo- and
      pathophysiologal situations. Astroglia is a polarized cell with EAAT localized at
      the end facing the neuropil while the end abutting the circulation is rich in
      AQP4. The water transport properties of EAAT suggest a new model for volume
      homeostasis of the extracellular space during neural activity.

PMID- 15561420
TI  - Some certainty for the "zone of uncertainty"? Exploring the function of the zona
      incerta.
AB  - The zona incerta (ZI), first described over a century ago by Auguste Forel as a
      "region of which nothing certain can be said," forms a collection of cells that
      derives from the diencephalon. To this day, we are still not certain of the
      precise function of this "zone of uncertainty" although many have been proposed,
      from controlling visceral activity to shifting attention and from influencing
      arousal to maintaining posture and locomotion. In this review, I shall outline
      the recent advances in the understanding of the structure, connectivity and
      functions of the ZI. I will then focus on a possible and often neglected global
      role for the ZI, one that links its diverse functions together. In particular, I
      aim to highlight the idea that the ZI forms a primal center of the diencephalon
      for generating direct responses (visceral, arousal, attention and/or posture
      locomotion) to a given sensory (somatic and/or visceral) stimulus. With this
      global role in mind, I will then address recent results indicating that abnormal
      ZI activity manifests in clinical symptoms of Parkinson disease.

PMID- 15561419
TI  - Potassium buffering in the central nervous system.
AB  - Rapid changes in extracellular K+ concentration ([K+](o)) in the mammalian CNS
      are counteracted by simple passive diffusion as well as by cellular mechanisms of
      K+ clearance. Buffering of [K+](o) can occur via glial or neuronal uptake of K+
      ions through transporters or K+-selective channels. The best studied mechanism
      for [K+](o) buffering in the brain is called K+ spatial buffering, wherein the
      glial syncytium disperses local extracellular K+ increases by transferring K+
      ions from sites of elevated [K+](o) to those with lower [K+](o). In recent years,
      K+ spatial buffering has been implicated or directly demonstrated by a variety of
      experimental approaches including electrophysiological and optical methods. A
      specialized form of spatial buffering named K+ siphoning takes place in the
      vertebrate retina, where glial Muller cells express inwardly rectifying K+
      channels (Kir channels) positioned in the membrane domains near to the vitreous
      humor and blood vessels. This highly compartmentalized distribution of Kir
      channels in retinal glia directs K+ ions from the synaptic layers to the vitreous
      humor and blood vessels. Here, we review the principal mechanisms of [K+](o)
      buffering in the CNS and recent molecular studies on the structure and functions
      of glial Kir channels. We also discuss intriguing new data that suggest a close
      physical and functional relationship between Kir and water channels in glial
      cells.

PMID- 15561421
TI  - Fear learning transiently impairs hippocampal cell proliferation.
AB  - We sought to determine whether contextual fear conditioning, a hippocampal
      dependent task, would affect neurogenesis in the dentate gyrus of the
      hippocampus, and if so, to identify which aspect of the training experience
      accounts for the change. The immediate shock deficit paradigm was used, together
      with bromodeoxyuridine immunohistochemistry, to isolate the contribution of
      different aspects of contextual fear conditioning to neurogenesis. Contextual
      fear learning caused a 33% decrease in the number of proliferating cells that was
      anatomically restricted to the dentate gyrus with no change in cell survival or
      differentiation. This attenuation was not related to exposure to the conditioned
      stimulus alone, the footshock unconditioned stimulus alone, or the expression of
      fear to the context after training. Instead, the effect of context conditioning
      on cell proliferation appears to be specifically due to the formation of an
      association between the context and shock during training, an amygdala dependent
      function.

PMID- 15561422
TI  - Role of the orbital cortex and of the serotonergic system in a rat model of
      obsessive compulsive disorder.
AB  - The serotonergic system and the orbitofrontal cortex have been consistently
      implicated in the pathophysiology of obsessive compulsive disorder. Yet, the
      relations between these two systems and the ways they interact in producing
      obsessions and compulsions are poorly understood. The present study tested the
      hypothesis that pathology of the orbitofrontal cortex leads to a dysregulation of
      the serotonergic system which is manifested in compulsive behavior, using a new
      rat model of this disorder. In the model, 'compulsive' behavior is induced by
      attenuating a signal indicating that a lever-press response was effective in
      producing food. We found that lesion to the rat orbital cortex led to a selective
      increase in compulsive lever-pressing that was prevented by the serotonin re
      uptake inhibitor, paroxetine, and was paralleled by an increase in the density of
      the striatal serotonin transporter, assessed using high affinity [3H]imipramine
      binding. These results suggest that the serotonergic system is involved in
      orbital lesion-induced compulsivity, and provide a possible account for the
      observed association between obsessions and compulsions and dysfunction of the
      orbitofrontal cortex and of the serotonergic system in obsessive compulsive
      disorder.

PMID- 15561423
TI  - Antennal tactile learning in the honeybee: effect of nicotinic antagonists on
      memory dynamics.
AB  - Restrained worker honeybees (Apis mellifera L.) are able to learn to associate
      antennal-scanning of a metal plate with a sucrose reinforcement delivered to the
      mouthparts. Learning occurs reliably in a single association of the two sensory
      stimuli. The involvement of nicotinic pathways in memory formation and retrieval
      processes was tested by injecting, into the whole brain through the median
      ocellus, either mecamylamine (0.6 microg per bee) or alpha-bungarotoxin (2.4 ng
      per bee). Saline served as a control. Mecamylamine injected 10 min before the
      retrieval test impairs the retention level tested 3 h and 24 h after single- or
      multi-trial learning. Retrieval tests performed at various times after the
      injection show that the blocking effect of mecamylamine lasts about 1 h. The drug
      has no effect on the reconsolidation or extinction processes. Mecamylamine
      injected 10 min before conditioning impairs single-trial learning but has no
      effect on five-trial learning and on the consolidation process. By contrast,
      alpha-bungarotoxin only impairs the formation of long-term memory (24 h) induced
      by the five-trial learning and has no effect on medium-term memory (3 h), on
      single-trial learning or on the retrieval process. Hence, owing to previous data,
      at least two kinds of nicotinic receptors seem to be involved in honeybee memory,
      an alpha-bungarotoxin-sensitive and an alpha-bungarotoxin-insensitive receptor.
      Our results extend to antennal mechanosensory conditioning the role of the
      cholinergic system that we had previously described for olfactory conditioning in
      the honeybee. Moreover, we describe here in this insect a pharmacological
      dissociation between alpha-bungarotoxin sensitive long-term memory and alpha
      bungarotoxin insensitive medium-term memory, the last one being affected by
      mecamylamine.

PMID- 15561424
TI  - Lengthening of G2/mitosis in cortical precursors from mice lacking beta-amyloid
      precursor protein.
AB  - The beta-amyloid precursor protein (APP) is expressed within the nervous system,
      even at the earliest stages of embryonic development when cell growth and
      proliferation is particularly important. In order to study the function of APP at
      these early developmental stages, we have studied the development of the cerebral
      cortex in both wild type and App-/- mutant mice. Here, we demonstrate that APP
      mRNA is expressed in cortical precursor cells and that APP protein is
      concentrated within their apical domains during interphase. However, during
      mitosis, APP re-localizes to the peripheral space surrounding the metaphase
      plate. In APP-deficient cortical precursors, the duration of mitosis is increased
      and a higher proportion of cortical precursor cells contained nuclei in late G2.
      We conclude that during cortical development APP plays a role in controlling cell
      cycle progression, particularly affecting G2 and mitosis. These observations may
      have important implications for our understanding of how APP influences the
      progression of Alzheimer's disease, since degenerating cortical neurons have been
      shown to up-regulate cell cycle markers and re-enter the mitotic cycle before
      dying.

PMID- 15561425
TI  - Immunohistochemical localization of the amino acid transporter SNAT2 in the rat
      brain.
AB  - SNAT2 is a neutral amino acid carrier that belongs to the system A family. Since
      its function in the nervous system remains unclear, we have analyzed its
      distribution in the rat CNS using specific antisera. Although SNAT2 is expressed
      widely in the CNS, it is enriched in the spinal cord and the brainstem nuclei,
      especially those of the auditory system. At the cellular level, SNAT2 was
      preferentially located in neuronal cell bodies and processes, although it was
      also strongly expressed in the meninges and ependyma. In astrocytes, the
      localization of SNAT2 was more restricted since it was intensely expressed in the
      perivascular end-feet, glia limitans, cerebellar astrocytes and Bergmann glia,
      but it was less intense in astrocytes of the cerebral parenchyma. Among neurons,
      the primary sensory neurons of the mesencephalic trigeminal nucleus appeared to
      be those that most strongly express SNAT2, but many other neurons, including
      cortical pyramidal cells and their dendrites were also intensely stained. In
      several regions the transporter was detected in axons, especially in the
      brainstem, and its presence in both dendrites and axons was confirmed by confocal
      microscopy and ultrastructural studies. However, while SNAT2 was observed in the
      large principal dendrites and the small distal dendrites, it was only found in
      axonal shafts and was excluded from terminals. Some glutamatergic neurons were
      among the more intensely labeled cells whereas SNAT2 was not detected on
      GABAergic neurons. The expression of SNAT2 partially coincides with that reported
      for SNAT1, especially in glutamatergic neurons. Hence, both proteins could
      fulfill complementary roles in replenishing glutamate pools and be differentially
      regulated under different physiological conditions. They also seem to co-localize
      in non-neuronal cells probably contributing to amino acid fluxes through the
      blood-brain barrier.

PMID- 15561426
TI  - In vivo neurogenesis in the dorsal vagal complex of the adult rat brainstem.
AB  - The dorsal vagal complex (DVC) encompasses the nucleus tractus solitarii (NTS),
      the dorsal motor nucleus of the vagus nerve (DMX) and the area postrema (AP),
      that altogether provide the major integrative center for the mammalian autonomic
      nervous system. The adult rat DVC has been reported to contain afferent-dependent
      concentration of the plasticity-promoting polysialylated form of neural cell
      adhesion molecule [J Neurosci 21 (2001) 4721; Eur J Neurosci 14 (2001) 1194].
      This prompted us to assess the occurrence of neurogenesis in the DVC of adult
      rats. Cumulative in vivo labeling of cell proliferation with i.p.
      bromodeoxyuridine (BrdU) injections was combined with phenotypic markers and
      confocal microscopy on serial brainstem sections throughout the DVC extent. In
      basal condition, sparse BrdU+ nuclei were selectively detected in the DVC
      according to a discrete and reproducible pattern. Some of them were found to
      colocalize with the neuronal markers doublecortin, HuC/D, or neuronal-specific
      antigen (NeuN), demonstrating that neurogenesis does occur within the DVC of
      adult rat. In the NTS, 10% of the BrdU+ nuclei were also NeuN+. A comparable
      proportion of astrogliogenesis was found in the DVC. Nestin immunohistochemistry
      yielded a highly specific labeling pattern at the border between AP and NTS.
      These data may relate to the neural stem cells that have been reported in the
      floor of the IVth ventricle [J Neurosci 16 (1996) 7599]. In order to assess a
      possible modulation of neurogenesis by afferent input in vivo, unilateral
      vagotomy was performed prior to cumulative BrdU treatment. Such DVC
      deafferentation triggered a large increase of BrdU incorporation in the
      ipsilateral DVC, which was associated with microglial proliferation in the DMX
      and with increased genesis of neurons and astrocytes in the NTS. These findings
      establish DVC as a novel model of adult neurogenesis that is reactive to
      deafferentation.

PMID- 15561427
TI  - The fast detection of rare auditory feature conjunctions in the human brain as
      revealed by cortical gamma-band electroencephalogram.
AB  - Natural environments typically contain temporal scatters of sounds emitted from
      multiple sources. The sounds may often physically stand out from one another in
      their conjoined rather than simple features. This poses a particular challenge
      for the brain to detect which of these sounds are rare and, therefore,
      potentially important for survival. We recorded gamma-band (32-40 Hz)
      electroencephalographic (EEG) oscillations from the scalp of adult humans who
      passively listened to a repeated tone carrying frequent and rare conjunctions of
      its frequency and intensity. EEG oscillations that this tone induced, rather than
      evoked, differed in amplitude between the two conjunction types within the 56-ms
      analysis window from tone onset. Our finding suggests that, perhaps with the
      support of its non-phase-locked synchrony in the gamma band, the human brain is
      able to detect rare sounds as feature conjunctions very rapidly.

PMID- 15561428
TI  - Glial cell line-derived neurotrophic factor (GDNF) is required for
      differentiation of pontine noradrenergic neurons and patterning of central
      respiratory output.
AB  - Genetic mutations affecting signaling by glial cell line-derived neurotrophic
      factor (GDNF) perturb development of breathing in mice and are associated with
      congenital central hypoventilation syndrome in humans. However, the role of GDNF
      in development of brainstem neurons that control breathing is largely unknown.
      The present study demonstrates that genetic loss of GDNF decreases the number of
      tyrosine hydroxylase (TH) neurons in the pontine A5 noradrenergic cell group, a
      major source of inhibitory input to the medullary respiratory pattern generator.
      This phenotype is associated with a significant increase in the frequency of
      central respiratory output recorded from the fetal medulla-spinal cord in vitro.
      In dissociate cultures of the A5 region from rat embryos, GDNF increases TH cell
      number and neurite growth without affecting total neuronal survival or
      proliferation of TH neurons. These effects of GDNF are inhibited by function
      blocking antibodies against endogenous brain-derived neurotrophic factor (BDNF),
      indicating that GDNF requires BDNF as a cofactor to stimulate differentiation of
      A5 neurons. Our findings demonstrate that GDNF is required for development of
      pontine noradrenergic neurons in vivo and indicate that defects in the A5 cell
      group may contribute to the effects of genetic disruption of GDNF signaling on
      respiratory control.

PMID- 15561429
TI  - Development of the norepinephrine transporter in the rat CNS.
AB  - The norepinephrine transporter (NET) plays a major role in regulating the actions
      of norepinephrine by removing norepinephrine from the synapse. Many studies
      suggest norepinephrine plays an important role in regulating development of the
      CNS, pointing to NET as an important factor in this process. We examined the
      ontogeny of NET expression in rat brain at 5, 10, 15, 20 and 25 days postnatally
      (PND) and in adults, using quantitative autoradiography with [3H]nisoxetine as
      ligand. At PND 5 and 10 most forebrain areas had low NET expression (1-2 fmol/mg
      tissue). By PND 15 most forebrain areas increased NET expression approximately
      five-fold compared with PND 10, levels generally similar to those found in the
      adult brain. In contrast, NET development in the brainstem exhibited elevated
      densities at PND 5, 10 and 20 that decreased in the adult. The locus coeruleus,
      in particular, had very high NET expression in the early postnatal period that
      decreased dramatically in the adult brain. These data illustrate a dynamic
      ontogenic profile for NET, characterized by developmental increases in forebrain
      structures and contrasting decreases in the brainstem. The early postnatal
      expression of NET in brainstem and the subsequent decrease or loss of NET
      expression with maturation suggest an important role for this transporter and for
      norepinephrine in the development of many brain regions. These studies also have
      important implications for use of drugs targeting the noradrenergic system in
      children and adolescents, such as antidepressants and drugs of abuse.

PMID- 15561430
TI  - Afferent subcortical connections into the motor cortical larynx area in the
      rhesus monkey.
AB  - In three rhesus monkeys (Macaca mulatta), the inferior motor cortex was explored
      by electrical stimulation for sites yielding vocal fold adduction. The retrograde
      tracer wheat germ-agglutinin-conjugated horseradish peroxidase was injected into
      the effective sites. Within the forebrain, retrogradely labeled cells were found
      in the claustrum, basal nucleus of Meynert, substantia innominata, extended
      amygdala, lateral and posterior hypothalamic area, field H of Forel, and a number
      of thalamic nuclei with the strongest labeling in the nuclei ventralis lateralis,
      ventralis posteromedialis, including its parvocellular part, medialis dorsalis
      and centrum medianum, and weaker labeling in the nuclei ventralis anterior,
      ventralis posterolateralis, intermediodorsalis, paracentralis, parafascicularis
      and pulvinaris anterior. In the midbrain, labeling was found in the deep
      mesencephalic nucleus, ventral tegmental area, and substantia nigra. In the lower
      brainstem, labeled cells were found in the pontine reticular formation, median
      and dorsal raphe nuclei, medial parabrachial nucleus, and locus coeruleus. The
      findings are discussed in terms of the possible role of these structures in
      voluntary vocal control.

PMID- 15561431
TI  - Afferent cortical connections of the motor cortical larynx area in the rhesus
      monkey.
AB  - The present study describes the cortical input into the motor cortical larynx
      area. The retrograde tracer horseradish peroxidase-conjugated wheat germ
      agglutinin was injected into the electrophysiologically identified motor cortical
      larynx area in three rhesus monkeys (Macaca mulatta). Retrogradely labeled cells
      were found in the surrounding premotor cortex (areas 6V and 6D), primary motor
      cortex (area 4), primary somatosensory cortex (areas 3, 1 and 2), anterior and
      posterior secondary somatosensory cortex and the probable homologue of Broca's
      area (areas 44 and 45); furthermore, labeling was found in the supplementary
      motor area, anterior and posterior cingulate cortex (areas 24 and 23), prefrontal
      and orbital frontal cortex (areas 8A, 46V, 47/12L, 47/12O, 13), agranular,
      dysgranular and granular insula as well as in the cortex within the upper bank of
      the middle third of the superior temporal sulcus (area TPO). The majority of
      these regions are reciprocally connected with the motor cortical larynx area
      [Brain Res 949 (2000) 23]. The laryngeal motor cortical input is discussed in
      relation to the connections of other motor cortical areas and its role in vocal
      control.

PMID- 15561432
TI  - Ultrastructural evidence that androgen receptors are located at extranuclear
      sites in the rat hippocampal formation.
AB  - Like estrogens in female rats, androgens can affect dendritic spine density in
      the CA1 subfield of the male rat hippocampus [J Neurosci 23:1588 (2003)].
      Previous light microscopic studies have shown that androgen receptors (ARs) are
      present in the nuclei of CA1 pyramidal cells. However, androgens may also exert
      their effects through rapid non-genomic mechanisms, possibly by binding to
      membranes. Thus, to investigate whether ARs are at potential extranuclear sites
      of ARs, antibodies to ARs were localized by light and electron microscopy in the
      male rat hippocampal formation. By light microscopy, AR immunoreactivity (-ir)
      was found in CA1 pyramidal cell nuclei and in disperse, punctate processes that
      were most dense in the pyramidal cell layer. Additionally, diffuse AR-ir was
      found in the mossy fiber pathway. Ultrastructural analysis revealed AR-ir at
      several extranuclear sites in all hippocampal subregions. AR-ir was found in
      dendritic spines, many arising from pyramidal and granule cell dendrites. AR-ir
      was associated with clusters of small, synaptic vesicles within preterminal axons
      and axon terminals. Labeled preterminal axons were most prominent in stratum
      lucidum of the CA3 region. AR-containing terminals formed asymmetric synapses or
      did not form synaptic junctions in the plane of section analyzed. AR-ir also was
      detected in astrocytic profiles, many of which apposed terminals synapsing on
      unlabeled dendritic spines or formed gap junctions with other AR-labeled or
      unlabeled astrocytes. Collectively, these results suggest that ARs may serve as
      both a genomic and non-genomic transducer of androgen action in the hippocampal
      formation.

PMID- 15561433
TI  - Indirect projections from the suprachiasmatic nucleus to major arousal-promoting
      cell groups in rat: implications for the circadian control of behavioural state.
AB  - The circadian clock housed in the suprachiasmatic nucleus (SCN) controls various
      circadian rhythms including daily sleep-wake cycles. Using dual tract-tracing, we
      recently showed that the medial preoptic area (MPA), subparaventricular zone
      (SPVZ) and dorsomedial hypothalamic nucleus (DMH) are well positioned to relay
      SCN output to two key sleep-promoting nuclei, namely, the ventrolateral and
      median preoptic nuclei. The present study examined the possibility that these
      three nuclei may link the SCN with wake-regulatory neuronal groups. Biotinylated
      dextran-amine with or without cholera toxin B subunit was injected into selected
      main targets of SCN efferents; the retrograde labeling in the SCN was previously
      analyzed. Here, anterograde labeling was analyzed in immunohistochemically
      identified cholinergic, orexin/hypocretin-containing and aminergic cell groups.
      Tracer injections into the MPA, SPVZ and DMH resulted in moderate to dense
      anterograde labeling of varicose fibers in the orexin field and the
      tuberomammillary nucleus. The locus coeruleus, particularly the dendritic field,
      contained moderate anterograde labeling from the MPA and DMH. The ventral
      tegmental area, dorsal raphe nucleus, and laterodorsal tegmental nucleus all
      showed moderate anterograde labeling from the DMH. The substantia innominata
      showed moderate anterograde labeling from the MPA. These results suggest that the
      MPA, SPVZ and DMH are possible relay nuclei for indirect SCN projections not only
      to sleep-promoting preoptic nuclei as previously shown, but also to wake
      regulatory cell groups throughout the brain. In the absence of major direct SCN
      projections to most of these sleep/wake-regulatory regions, indirect neuronal
      pathways probably play an important role in the circadian control of sleep-wake
      cycles and other physiological functions.

PMID- 15561434
TI  - Synaptic targets of calretinin-containing axon terminals in macaque monkey
      prefrontal cortex.
AB  - The coordinated activity of specific populations of pyramidal cells and GABA
      containing, local circuit neurons in the primate prefrontal cortex (PFC) appears
      to be critical for working memory. Different subclasses of GABA-containing
      neurons can be distinguished by their content of the calcium-binding proteins
      parvalbumin (PV) and calretinin (CR). The postsynaptic targets of PV-containing
      cells have been well characterized in the primate PFC, but the postsynaptic
      targets of CR-containing neurons in this cortical region remain unknown. In the
      present study, we used immuno-electron microscopy to examine the synaptic type
      and postsynaptic targets of CR-immunoreactive (IR) axon terminals in the
      superficial and deep layers of macaque monkey PFC. Labeled axon terminals formed
      both symmetric and asymmetric synapses. Within the superficial layers, 93% of the
      synapses formed by CR-IR were symmetric, whereas in the deep layers the labeled
      axon terminals forming synapses were more evenly divided between symmetric (57%)
      and asymmetric (43%). The primary postsynaptic target of these two populations of
      CR-IR axon terminals also differed; unlabeled dendritic shafts were the
      predominant target of the symmetric synapses, whereas dendritic spines were the
      most common target of the asymmetric synapses. In addition, the mean cross
      sectional area of the terminals forming asymmetric synapses was significantly
      larger than that of the terminals forming symmetric synapses. The presence of CR
      IR asymmetric synapses suggested that they might arise from neurons that do not
      utilize GABA; indeed, dual-label fluorescent immunocytochemistry revealed that a
      subpopulation (23%) of CR-containing neurons in monkey PFC were not GABA-IR.
      These findings indicate that the synaptology of CR-containing neurons is more
      heterogeneous than that of PV-containing cells and suggests that the
      contributions of CR-containing neurons to cognitive processes mediated by the PFC
      may be more diverse.

PMID- 15561435
TI  - Alterations in glutamatergic and gabaergic ion channel activity in hippocampal
      neurons following exposure to the abused inhalant toluene.
AB  - Toluene, a representative member of the large class of abused inhalants,
      decreases neuronal activity and depresses behavior in both animals and humans.
      The sites of action of toluene are not completely known but recent studies
      suggest that ion channels that regulate neuronal excitability may be particularly
      sensitive. Previous studies with recombinant receptors showed that toluene
      decreases currents carried by N-methyl-D-aspartate (NMDA)-glutamate receptors
      without affecting those gated by non-NMDA receptors. In addition, toluene
      increases currents generated by GABA and glycine receptors. In the present study,
      primary cultures of rat hippocampal neurons were used to investigate the effects
      of acute and chronic toluene exposure on native excitatory and inhibitory ligand
      gated ion channels. Toluene dose-dependently inhibited NMDA-mediated currents
      (IC50 1.5 mM) but had no effect on responses evoked by the non-NMDA agonist
      kainic acid. Prolonged treatment of neurons with toluene (1 mM; 4 days) increased
      whole-cell responses to exogenously applied NMDA, reduced those evoked by GABA
      but did not alter responses generated by kainic acid. Immunoblot analysis
      revealed that prolonged toluene exposure increased levels of NR2A and NR2B NMDA
      receptor subunits with no change in NR1. Immunohistochemical analysis with
      confocal imaging showed that toluene-treated neurons had significant increases in
      the density of NR1 subunits as compared with control neurons. Toluene exposure
      increased the amplitude of synaptic NMDA currents and decreased those activated
      by GABA. The results from this study suggest that toluene induces compensatory
      responses in the functional expression of ion channels that regulate neuronal
      excitability.

PMID- 15561436
TI  - The linoleic acid derivative FR236924 facilitates hippocampal synaptic
      transmission by enhancing activity of presynaptic alpha7 acetylcholine receptors
      on the glutamatergic terminals.
AB  - The present study aimed at understanding the effect of FR236924, a newly
      synthesized linoleic acid derivative with cyclopropane rings instead of cis
      double bonds, on hippocampal synaptic transmission in both the in vitro and in
      vivo systems. FR236924 increased the rate of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid receptor-mediated miniature excitatory postsynaptic
      currents, without affecting the amplitude, triggered by nicotine in CA1 pyramidal
      neurons of rat hippocampal slices, that is inhibited by GF109203X, a selective
      protein kinase C (PKC) inhibitor or alpha-bungarotoxin, an inhibitor of alpha7
      acetylcholine (ACh) receptors. FR236924 stimulated glutamate release from rat
      hippocampal slices and in the hippocampus of freely behaving rats, and the effect
      was also inhibited by GF109203X or alpha-bungarotoxin. FR236924 induced a
      transient huge potentiation followed by a long-lasting potentiation in the slope
      of field excitatory postsynaptic potentials recorded from the CA1 region of rat
      hippocampal slices, and the latter effect was blocked by GF109203X or alpha
      bungarotoxin. Likewise, the compound persistently facilitated hippocampal
      synaptic transmission in the CA1 region of the intact rat hippocampus. It is
      concluded from these results that FR236924 stimulates glutamate release by
      functionally targeting presynaptic alpha7 ACh receptors on the glutamatergic
      terminals under the influence of PKC, responsible for the facilitatory action on
      hippocampal synaptic transmission. This may provide evidence for a link between
      cis-unsaturated free fatty acids and presynaptic alpha7 ACh receptors in
      hippocampal synaptic plasticity.

PMID- 15561437
TI  - Evidence for a selective prefrontal cortical GABA(B) receptor-mediated inhibition
      of glutamate release in the ventral tegmental area: a dual probe microdialysis
      study in the awake rat.
AB  - Glutamate-containing pyramidal neurons in the medial prefrontal cortex (mPfc)
      project to the ventral tegmental area (VTA) where they synapse on
      mesocorticolimbic dopamine containing cell bodies and GABA interneurons. In the
      present study we employed dual probe microdialysis in intact conscious rat brain
      to investigate the effects of intra-mPfc perfusion with a depolarising
      concentration of potassium chloride (KCl) (100 mM, 20 min) alone and in the
      presence of local GABA(A) and GABA(B) receptor blockade on VTA glutamate release.
      Intra-mPfc KCl transiently increased VTA glutamate release (+71.48+/-14.29%, 20
      min). Intra-mPfc perfusion with a concentration of the GABA(A) receptor
      antagonist bicuculline (10 microM, 120 min) did not influence the intra-mPfc KCl
      induced increase in VTA glutamate release (+102.35+/-33.61%, 20 min). In
      contrast, intra-mPfc perfusion with a concentration of the GABA(B) receptor
      antagonist CGP35348 (100 microM, 120 min) which when given alone did not
      influence basal glutamate levels in the VTA was associated with an enhanced KCl
      induced stimulation of VTA glutamate release (+375.19+/-89.69%, 40 min).
      Furthermore, this enhancement was reversed in the presence of the selective
      GABA(B) receptor agonist baclofen (10 microM, 120 min). The present findings
      suggest a key role for the prefrontal cortex in the regulation of glutamate
      release in the VTA. Furthermore, we demonstrate a selective cortical GABA(B)
      receptor-mediated inhibition of glutamate transmission in the VTA. These findings
      may be important in the context of abnormalities in amino acid neurotransmission
      at the network level in schizophrenia.

PMID- 15561438
TI  - TRPV2, a capsaicin receptor homologue, is expressed predominantly in the
      neurotrophin-3-dependent subpopulation of primary sensory neurons.
AB  - TRPV2, a member of transient receptor potential ion channels, responds to high
      threshold noxious heat, but neither to capsaicin nor to proton. Although TRPV2 is
      expressed in medium- to large-sized dorsal root ganglion (DRG) neurons with
      myelinated fibers in adult rodents, little is known about the neurotrophin
      dependence of TRPV2-positive neurons in the developing and adult DRGs of mice. In
      the present study, using immunohistochemistry, we found that TRPV2 was first
      expressed in DRG neurons at embryonic day (E) 11.5, when neither TRPV1 nor TRPM8
      was detected yet. Double-immunofluorescence staining revealed that tyrosine
      kinase receptor C (TrkC) was expressed in most of TRPV2-positive DRG neurons at
      E11.5 and E13.5. In addition, the percentage of TRPV2-positive neurons in the
      total DRG neurons at E13.5 reached the same as that of adulthood. In adult DRGs,
      TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons,
      respectively. These results suggest that TRPV2 is expressed predominantly in the
      NT-3-dependent subpopulation of DRG neurons throughout development and in adult
      mice.

PMID- 15561439
TI  - Co-expression patterns of the neuropeptides vasoactive intestinal peptide and
      cholecystokinin with the transduction molecules alpha-gustducin and T1R2 in rat
      taste receptor cells.
AB  - Taste receptor cells are primary sensory receptors utilized by the nervous system
      to detect the presence of gustatory stimuli in the oral cavity. These cells are
      particularly heterogeneous and may be divided into various subtypes based on
      morphological, histochemical, or physiological criteria. One example is the
      heterogeneous expression of neuropeptides, such as cholecystokinin and vasoactive
      intestinal polypeptide. These peptides are hypothesized to participate in the
      transduction processes. To pursue examination of this hypothesis, this study
      explored the relationship of peptide expression with two important and mostly non
      overlapping transductive elements--the taste-specific G protein gustducin,
      involved in bitter and sweet transduction cascades, and the seven transmembrane
      taste receptor T1R2, hypothesized to respond to sweet compounds. Double labeling
      experiments were performed on taste buds of the posterior rat tongue combining
      immunocytochemistry for peptide expression and in situ hybridization experiments
      for either gustducin or T1R2 expression. Additionally, vasoactive intestinal
      peptide (VIP)-expression in posterior taste receptor cells was confirmed using
      the technique of RT-PCR. More than half (56%) of the CCK-expressing taste
      receptor cells co-expressed alpha-gustducin mRNA whereas far fewer (15%) co
      expressed T1R2 mRNA. A majority of VIP-expressing taste receptor cells co
      expressed alpha-gustducin mRNA (60%) whereas only 19% of these cells co-expressed
      T1R2 mRNA. More remarkable was the observation that these two peptides displayed
      almost identical expression patterns with these signal transduction molecules,
      suggesting that peptides are not randomly expressed with relation to signal
      transduction molecules. This observation supports the hypothesis that peptides
      may play roles in transduction. Further physiological exploration will be
      required to elucidate the nature of these roles.

PMID- 15561440
TI  - Frequency bands and spatiotemporal dynamics of beta burst stimulation induced
      afterdischarges in hippocampus in vivo.
AB  - Temporal and spatial characteristics of hippocampal neuronal network activation
      are modified during epileptiform afterdischarges. We developed a beta burst
      stimulation protocol to investigate subregional variations and substrates of
      rhythmic population spike discharges in vivo in urethane anesthetized Wistar rat
      hippocampus with a 14-electrode recording array and extracellular single
      electrode recordings. Our 64 pulse beta burst stimulation protocol was
      constructed from electrical pulses delivered at intervals corresponding to beta
      (14-25 Hz), Delta (2 Hz), and slow (0.5 Hz) frequencies. In each experiment these
      interleaved pulses were all repeated four times with unchanged intervals.
      Stimulation of either perforant path or fimbria fornix induced a prolonged
      afterdischarge pattern peaking at 200 Hz fast, 20 Hz beta, and 2 Hz Delta
      frequencies. Analysis of variance confirmed that the response pattern of the
      discharges remained constant regardless of the stimulation beta frequency. Within
      the afterdischarge the fast frequencies were restricted to independent
      hippocampal subfields whereas beta and slow frequencies correlated across the
      subfields. Current source density (CSD) analysis revealed that the original
      signal propagation through subfields of the hippocampus was compromised during
      the beta burst stimulation induced afterdischarge. In addition, the CSD profile
      of the epileptiform afterdischarge was consistently similar across the different
      experiments. Time-frequency analysis revealed that the beta frequency
      afterdischarge was initiated and terminated at higher gamma (30-80 Hz)
      frequencies. However, the alterations in the CSD profile of the hippocampus
      coincided with the beta frequency dominated discharges. We propose that
      hippocampal epileptiform activity at fast, beta and Delta frequencies represents
      coupled oscillators at respectively increasing spatial scales in the hippocampal
      neuronal network in vivo.

PMID- 15561441
TI  - Polysynaptic olfactory pathway to the ipsi- and contralateral entorhinal cortex
      mediated via the hippocampus.
AB  - Interactions between olfactory cortices and the hippocampus support sensory
      discrimination and spatial learning functions. The olfactory input accesses the
      hippocampal formation via a polysynaptic pathway mediated by the lateral and
      rostral entorhinal cortex (EC). We recently demonstrated that following
      repetitive stimulation of the lateral olfactory tract (LOT) at 2-8 Hz, a delayed
      response (onset at circa 60 ms) was evoked in the caudal portion of the EC,
      identified as medial EC, that does not receive a direct olfactory input. By
      performing simultaneous laminar profile analysis in the EC and in different
      hippocampal subfields, we conclusively demonstrate that the delayed EC response
      evoked by repetitive ipsilateral LOT stimulation is headed by the sequential
      activation of the dentate gyrus and the CA3/CA1 subfields in the septal and
      temporal hippocampus. Repetitive stimulation of the contralateral LOT also
      induced an EC response that peaked at 76.28+/-2.42 ms (n=15). Current source
      density analysis and time-delay analysis of simultaneous field potential laminar
      profiles performed from the EC and from DG, CA3 and CA1 hippocampal subfields
      suggested that the contralateral EC response is mainly carried by an
      intrahippocampal CA3-CA3 commissural pathway. Contralateral LOT stimulation also
      induced a later EC component (delay >100 ms) generated in the superficial layers,
      mediated either by local associative interactions or by extrahippocampal
      circuits. The opportunity to activate the ipsi- and contralateral olfactory
      pathways in the same experiment and to record field potentials profiles
      simultaneously in different structures of both hemispheres in the isolated guinea
      pig brain confirms that this preparation is unique and is particularly suitable
      for investigating the system physiology of the limbic region. The present study
      demonstrates that patterned stimulation of the olfactory input that mimics
      sniffing patterns during odor discrimination induces a diffuse activation of both
      ipsi- and contralateral hippocampi and ECs. The findings contribute to the
      understanding the physiological mechanisms that underlie associative interactions
      between olfactory and non-olfactory cortical inputs converging into the mesial
      temporal region.

PMID- 15561442
TI  - Neural correlates of social odor recognition and the representation of individual
      distinctive social odors within entorhinal cortex and ventral subiculum.
AB  - Recognition of individual conspecifics is important for social behavior and
      requires the formation of memories for individually distinctive social signals.
      Individual recognition is often mediated by olfactory cues in mammals, especially
      nocturnal rodents such as golden hamsters. In hamsters, this form of recognition
      requires main olfactory system input to the lateral entorhinal cortex (LEnt).
      Here, we tested whether neurons in LEnt and the nearby ventral subiculum (VS)
      would show cellular correlates of this natural form of recognition memory. Two
      hundred ninety single neurons were recorded from both superficial (SE) and deep
      layers of LEnt (DE) and VS while male hamsters investigated volatile odorants
      from female vaginal secretions. Many neurons encoded differences between female's
      odors with many discriminating between odors from different individual females
      but not between different odor samples from the same female. Other neurons
      discriminated between odor samples from one female and generalized across
      collections from other females. LEnt and VS neurons showed enhanced or suppressed
      cellular activity during investigation of previously presented odors and in
      response to novel odors. A majority of SE neurons decreased firing to odor
      repetition and increased activity to novel odors. In contrast, DE neurons often
      showed suppressed activity in response to novel odors. Thus, neurons in LEnt and
      VS of male hamsters encode information that is critical for the identification
      and recognition of individual females by odor cues. This study reveals cellular
      mechanisms in LEnt and VS that may mediate a natural form of recognition memory
      in hamsters. These neuronal responses were similar to those observed in rats and
      monkeys during performance in standard recognition memory tasks. Consequently,
      the present data extend our understanding of the cellular basis for recognition
      memory and suggest that individual recognition requires similar neural mechanisms
      as those employed in laboratory tests of recognition memory.

PMID- 15561444
TI  - Perception of drug addiction among Turkish university students: causes, cures,
      and attitudes.
AB  - In this paper, university students' beliefs about different causes of drug
      addiction and cures for it were investigated. Principal component analysis (PCA)
      with Causes of Drug Abuse Scale (CADAS) revealed four components: problems and
      coping, sensation seeking, social environment, and disposition. PCA with Cures
      for Drug Abuse Scale (CUDAS) produced four components: help seeking and
      avoidance, self-change, social activity, and change. Separate MANOVAs were
      performed and significant gender differences were found between two of CADAS' and
      three of CUDAS' components. Analysis on attitude scale revealed gender and drug
      main effects and an interaction effect. Men had more positive attitudes toward
      "drug" vignette. The most negative attitudes were found toward "heroin" vignette
      and the most positive attitudes were found toward the "cannabis" vignette.
      Results indicated that those who has known a drug user had more positive
      attitudes.

PMID- 15561443
TI  - Active medullary control of atonia in week-old rats.
AB  - Muscle atonia is a central feature of adult REM sleep which has recently been
      demonstrated to be a component of sleep in rats as young as 2 days of age (P2).
      The neural generation of atonia, which depends on mesopontine and medullary
      structures, is not fully understood in adults and has never been described in
      infants. In the present experiments we used electrical stimulation in
      decerebrated pups to identify an inhibitory area within the medial medulla of P7
      10 rats. Muscle tone inhibition was consistently found on or near the midline
      within the ventromedial medulla, dorsal to the inferior olive, in an area that
      includes the nucleus gigantocellularis, nucleus paramedianus, and raphe obscurus.
      Chemical infusions in the same region revealed inhibitory responses to quisqualic
      acid but not to carbachol or corticotropin-releasing factor. Next, extracellular
      recordings within the medullary inhibitory area revealed neurons with atonia-on
      profiles; tone-on neurons were also found, typically at more lateral sites.
      Finally, in non-decerebrated pups, chemical lesions within the inhibitory area
      resulted in significant reductions in atonia durations, as well as decoupling of
      atonia from a second component of infant sleep, myoclonic twitching;
      specifically, twitches occasionally occurred during periods of high muscle tone,
      a condition reminiscent of "REM without atonia" as described in adults. In
      summary, we document the existence of an area within the ventromedial medulla of
      infant rats that (i) causes atonia when stimulated; (ii) contains units that
      exhibit atonia-related discharge profiles during sleep-wake cycling; and (iii)
      when lesioned, results in the partial loss of atonia and decoupling of the
      components of sleep. All together, these findings demonstrate that muscle atonia
      is actively regulated very early in ontogeny.

PMID- 15561445
TI  - Effects of different nicotine replacement therapies on postcessation
      psychological responses.
AB  - Transdermal nicotine patch (TN) and nicotine nasal spray (NS) are both
      efficacious forms of smoking cessation treatment, but have different
      pharmacokinetic properties and modes of action. To understand better
      psychological responses to treatment, we investigated the effects of TN versus NS
      on positive affect, negative affect, and withdrawal symptoms during treatment.
      Participants were randomly assigned to receive TN (n=172) or NS (n=163) plus
      seven sessions of behavioral counseling, and completed self-report questionnaires
      at pretreatment and during treatment. TN participants, but not NS participants,
      reported significant increases in positive affect during treatment. Increases in
      negative affect and withdrawal were observed, independent of treatment. Only
      changes in negative affect predicted relapse by the end of the treatment phase.
      These findings indicate that, although TN may enhance positive affect for smokers
      in treatment compared with NS, only changes in negative affect predict treatment
      outcome.

PMID- 15561446
TI  - Decreased substance use following increases in alternative behaviors: a
      preliminary investigation.
AB  - Research derived from behavioral economic theories has demonstrated reciprocal
      links between substance use and engagement in substance-free activities. The
      current study used an experimental manipulation to further investigate the
      relationship between substance use and substance-free behaviors in a nonclinical
      sample of 133 young adults. Participants completed surveys on substance use and
      engagement in specific substance-free behaviors (exercise and creative behaviors)
      on two occasions separated by a 28-day interval. During the 4 weeks separating
      assessments, the 105 participants who reported recent substance use were randomly
      assigned to one of three experimental conditions with corresponding behavioral
      instructions: substance use reduction (SR), activity increase (AI), and a no
      change control. Participants assigned to both the SR and AI conditions reported a
      significant decrease in their substance use behavior. These results are
      consistent with previous studies in demonstrating that decreases in substance use
      can be achieved by increasing engagement in substance-free behaviors.

PMID- 15561447
TI  - The Significant Other Checklist: measuring the problems experienced by family
      members of drug users.
AB  - Historically, much attention has been given to the multifaceted problems
      experienced by drug abusers. Recently, greater attention has been given to the
      family members of drug abusers, but unfortunately, most of this attention has
      focused on family relationships and has overlooked the problems experienced by
      family members of drug users (DUs). To date, there is no psychometrically sound,
      multidimensional assessment tool available to systematically assess the economic,
      behavioral, and psychological problems encountered by these family members. This
      study presents the findings associated with the initial measurement development
      phase of such an assessment tool. The initial results are promising, suggesting
      that the Significant Other Checklist (a) has reasonable initial subscale
      reliability estimates, (b) assesses problem domains that are relevant to family
      members of DUs, and (c) is able to identify important group similarities and
      differences among family members of DUs.

PMID- 15561448
TI  - Applicability of the Fagerstrom Test for Nicotine Dependence in smokers with
      schizophrenia.
AB  - Up to 90% of individuals with schizophrenia smoke cigarettes, and many show signs
      of heavy dependence. Although the severity of nicotine dependence is often
      measured by the six-item Fagerstrom Test for Nicotine Dependence (FTND), this
      measure, in its current form, may not be as appropriate in this population--or in
      others who's smoking is regulated by others--as in the general population due to
      differences in smoking patterns, living arrangements, and daily routines. These
      factors may produce an underestimate of nicotine dependence, which may have
      clinical implications for successful medical detoxification if the FTND scores
      are used to guide the dosage of nicotine replacement medication. Data indicate
      poor internal consistency reliability (alpha=.4581) and a factor pattern lacking
      simple structure (i.e., two nonmeaningful factors/components with substantial
      cross loadings) when administered to smokers with schizophrenia. Specific
      examples of problematic items and how these may contribute to an underestimate of
      tobacco dependence severity are discussed, as well as ways to modify the FTND to
      be more appropriate for this population.

PMID- 15561449
TI  - A placebo controlled randomized trial of the effects of phenylpropanolamine and
      nicotine gum on cessation rates and postcessation weight gain in women.
AB  - With smoking prevalence rates beginning to decline, studies designed to promote
      cessation in more challenging populations, like weight-concerned smokers, warrant
      attention. This study assessed the efficacy of two forms of pharmacotherapy
      [nicotine and phenylpropanolamine (PPA) gums] in addition to a 13-week cognitive
      behavioral smoking cessation program targeted for women. Participants were 439
      females who met rigorous screening criteria and were randomized to one of the
      three treatment intervention groups (PPA gum, nicotine gum, or placebo gum). All
      participants attended a 13-week cognitive behavioral smoking cessation program
      and were given specific instructions on gum chewing. At posttest (13 weeks), and
      6- and 12-month follow-ups, body weight and point prevalence abstinence were
      assessed. Analyses to determine potential differences between treatment groups on
      weight change and cessation rates were performed. Results indicated that neither
      change in body weight nor cessation rates significantly differed between groups.
      Attendance to sessions did appear to consistently increase the likelihood of
      quitting smoking at posttest and at each of the follow-ups. These results suggest
      that although the pharmacological interventions had no effect on cessation rates
      and postcessation weight gain, the behavioral component of the intervention was
      effective in increasing the odds of quitting smoking in weight-concerned women.
      Future efforts should focus on increasing adherence to behavioral program
      components, particularly session attendance.

PMID- 15561450
TI  - Childhood IQ, smoking, and cognitive change from age 11 to 64 years.
AB  - We investigated whether smoking is a risk factor for relative cognitive decline
      from age 11 to 64 years. The potentially confounding effects of childhood IQ,
      occupational status, level of education, presence of heart disease, hypertension,
      and lung function were examined. Subjects were nondemented and living
      independently. They were all born in 1936, had been participants in the same
      Scottish national IQ survey in 1947, and were reexamined at age about 64 years in
      2000-2002. Current smokers and nonsmokers had significantly different mental test
      scores at age 64. This difference remained after adjustment for childhood IQ.
      Multiple linear regression identified childhood IQ, level of education,
      occupational code, lung function, and smoking history as significant independent
      predictors of mental function at age 64. In this sample, smoking makes a small
      (<1% variance) independent negative contribution to cognitive aging.

PMID- 15561451
TI  - Differential effects of MDMA, cocaine, and cannabis use severity on distinctive
      components of the executive functions in polysubstance users: a multiple
      regression analysis.
AB  - Executive functioning impairments have been demonstrated following consumption of
      drugs of abuse. These executive impairments could play an important role on the
      development of the addictive process and rehabilitation of substance abusers.
      Recent neuropsychological models of executive functioning assume a multicomponent
      organization of these processes, suggesting different functions could contribute
      differentially to performance on executive tasks. The aim of this study was to
      analyze the relationship between severity of consumption of different drugs and
      neuropsychological performance on tasks sensitive to impairment in the executive
      subprocesses of working memory, response inhibition, cognitive flexibility, and
      abstract reasoning. Instruments sensitive to impairment in these four components
      were administered to 38 polysubstance abusers along with a severity of drug
      consumption interview. Multiple regression analyses were used. Results showed a
      differential impact of severity of MDMA abuse on working memory and abstract
      reasoning indices, of cocaine severity on an inhibitory control index and of
      cannabis on a cognitive flexibility index. Metabolic reorganization of monoamine
      frontal-subcortical pathways after drug exposure are proposed as possible
      explanations for these impairments.

PMID- 15561452
TI  - The criteria for causation of alcohol in violent injuries based on emergency room
      data from six countries.
AB  - This paper is based on data using similar methods collected from patients at 30
      emergency rooms (ERs) in six countries. These data were analyzed with the goal of
      determining whether alcohol is a likely cause of violence through an application
      of criteria outlined by Bradford Hill. Analyses were conducted by comparing
      various measures of alcohol involvement in violent versus accidental injuries.
      The results supported temporal sequence of events and specificity. The odds
      ratios of violent versus accidental injury for a blood alcohol concentration
      (BAC) over 80 mg% were significant for each country, ranging from 2.77 for Mexico
      to 9.45 for Canada, which supports both the strength of associations and the
      consistency of findings. No third variables were found from the logistic
      regression analysis that better explain the relationships between alcohol and
      violence. A significant dose-response relationship between BAC level and violence
      was also found. All analyses conducted point to a causal role of alcohol in
      injuries related to violence.

PMID- 15561453
TI  - Cognitive versus behavioral treatment of concurrent alcohol dependence and
      agoraphobia: a pilot study.
AB  - With the growing awareness of the prevalence of anxiety disorders among alcohol
      abusers there is a need for effective cognitive--behavioral treatments (CBTs).
      This study is a pilot investigation comparing two treatments for concurrent
      alcohol dependence and panic disorder with agoraphobia. A 10-session behavioral
      treatment (BT), consisting of five sessions treating alcohol dependence and five
      sessions treating panic disorder with agoraphobia, was compared to a 10-session
      cognitive treatment (CT) that addressed the dysfunctional cognitions mediating
      the alcohol problem and anxiety symptoms. There were no group differences in
      frequency or quantity of alcohol consumption or in anxiety symptoms posttreatment
      or at a 1-year follow-up in a sample of 14 subjects who completed the study. Both
      groups showed within-group improvements on measures of both alcohol and anxiety
      symptomatology. Approximately one-third of the subjects made clinically relevant
      gains on both alcohol and anxiety symptoms. A brief BT for concurrent alcohol
      dependence and agoraphobia appears encouraging.

PMID- 15561454
TI  - Incorporating social anxiety into a model of college student problematic
      drinking.
AB  - College problem drinking and social anxiety are significant public health
      concerns with highly negative consequences. College students are faced with a
      variety of novel social situations and situations encouraging alcohol
      consumption. The current study involved developing a path model of college
      problem drinking, including social anxiety, in 316 college students referred to
      an alcohol intervention due to a campus alcohol violation. Contrary to
      hypotheses, social anxiety generally had an inverse relationship with problem
      drinking. As expected, perceived drinking norms had important positive, direct
      effects on drinking variables. However, the results generally did not support the
      hypotheses regarding the mediating or moderating function of the valuations of
      expected effects and provided little support for the mediating function of
      alcohol expectancies in the relations among social anxiety and alcohol variables.
      Therefore, it seems that the influence of peers may be more important for college
      students than alcohol expectancies and valuations of alcohol's effects are.
      College students appear to be a unique population in respect to social anxiety
      and problem drinking. The implications of these results for college prevention
      and intervention programs were discussed.

PMID- 15561455
TI  - Do school surroundings matter? Alcohol outlet density, perception of adolescent
      drinking in public, and adolescent alcohol use.
AB  - The aim of the present study was to investigate the relationship between alcohol
      outlet density, perception of adolescent drinking in public (both assessed at the
      school level), and adolescent drinking and drunkenness at individual level.
      Hierarchical linear regression models were calculated based on data from 1194
      ninth graders in Switzerland (mean age=15.3, S.D.=0.7) and their schoolmasters
      (n=61). Apart from the positive main effects, the results reveal a negative
      interaction of alcohol outlet density and perception of adolescent drinking in
      public in predicting individual alcohol use among adolescents. In regions with a
      high density of shops, it appears that the schoolmasters' perception reflects the
      general drinking norm of the area where the school is located rather than the
      actual drinking level of adolescents. More research is needed, particularly in
      Europe and among adolescent populations, to reach a better understanding of
      school level predictors of adolescent alcohol use.

PMID- 15561456
TI  - Motivation for change in alcohol dependent outpatients from Brazil.
AB  - The general aim of this study was to investigate the reliability and factor
      structure of the stages of change readiness and treatment eagerness scale
      (SOCRATES) in 326 outpatients with alcohol dependence. The questionnaire was
      translated and cross-culturally adapted into Portuguese and back-translated to
      English. The confirmatory factor analysis showed that two correlated factors
      provided the best fit for the data.

PMID- 15561457
TI  - Factors associated with former smokers among female adolescents in rural
      Virginia.
AB  - We examined multiple ecological factors (individual, family, peer, school, and
      community) associated with female adolescent former smokers (FS), current smokers
      (CS), and never smokers (NS) in a sample of 2029 seventh to twelfth grade girls
      living in a rural area of Virginia. We were particularly interesting in examining
      variables related to FS. Compared to CS, FS reported lower levels of delinquency,
      less coping by taking drugs, less availability of cigarettes, and less alcohol
      and marijuana use. They also reported less depression, fewer suicidal thoughts,
      and fewer suicide attempts than CS. FS reported spending more time in community
      clubs, had higher self-esteem, obtained higher grades, had more parental
      monitoring, more parent attachment, and more school attachment than CS.
      Logistical regression analysis predicting current or former smoking status
      revealed significant effects on coping by taking drugs, alcohol use, depression,
      grades, parental monitoring, and perceived availability of cigarettes. The
      findings have implications for smoking intervention programs with adolescent
      girls in rural areas.

PMID- 15561458
TI  - Tobacco-reporting validity in an epidemiological drug-use survey.
AB  - We compared responses to questions about tobacco use and passive exposure to
      smoking with biological tests for cotinine in order to estimate tobacco-reporting
      validity in an epidemiological survey on drug use. Respondents identified via
      multistage sampling (n=627) completed household surveys that were administered
      using an Audio Computer-Assisted Self-Interview (ACASI) procedure. Following the
      survey, respondents were asked to participate in drug testing. Saliva (oral
      fluid) was used to screen for the presence of cotinine, a major metabolite of
      tobacco. Hair, urine, and oral fluid testing were used to detect the presence of
      illicit drugs such as amphetamines, cocaine, heroin, and marijuana. While
      underreporting of tobacco was relatively rare, estimates from this recent study
      suggest that it may be increasing over time. Even after adjusting for passive
      exposure, self-report sensitivity estimates were still well below the 90% level
      suggested in prior reviews. Underreporting of marijuana and race/ethnicity showed
      a strong association with underreporting of tobacco use, suggesting that factors
      associated with the underreporting of illicit substance use parallel those
      associated with the underreporting of tobacco use.

PMID- 15561459
TI  - Compulsive behavior in tobacco users.
AB  - Addictions have been associated with compulsive behaviors, which serve to reduce
      emotional distress. Tobacco use has been associated with increased adverse moods
      such as anxiety. Nicotine has established anxiolytic effects through modulation
      of central neurotransmitters, including monoamines. Both obsessive-compulsive
      behaviors and tobacco use have both been associated with dysfunction in
      orbitofrontal-subcortical circuits. This study demonstrated greater intensity of
      compulsive behaviors (as measured by the Yale-Brown Obsessive Compulsive Scale [Y
      BOCS]) in tobacco users compared to nonusers, which was not due to demographic
      influences or use of other psychoactive drugs. Both the frequency of tobacco use
      and level of overall emotional distress correlated positively with the severity
      of compulsive symptoms. The results are consistent with tobacco use as a form of
      self-medicating compulsive symptoms, likely through monoamine modulation of
      orbitofrontal-subcortical circuits.

PMID- 15561460
TI  - French general practitioners' prescribing high-dosage buprenorphine maintenance
      treatment: is the existing training (good) enough?
AB  - In France, since 1996, any general practitioner (GP) can prescribe high-dosage
      buprenorphine maintenance treatment (BMT) for opioid-dependent patients. The
      health authorities initially provided mandatory specific training, but since
      1998, such training is only delivered by specialized networks and the
      pharmaceutical industry. Among a random sample of GPs from southeastern France
      (N=345), we found that many untrained GPs, as well as a significant minority of
      trained GPs, were likely to prescribe an ineffective dosage of buprenorphine or a
      potentially dangerous treatment (BMT+a short half-life benzodiazepine). These
      results highlight the necessity to edit clear guidelines, especially concerning
      situations of polyaddiction and psychiatric comorbidity, and to extend and
      improve BMT training in France with a renewed involvement of health authorities
      for quality control of such training. They even suggest that GPs' participation
      to specialized training sessions should become a mandatory prerequisite for
      prescribing BMT.

PMID- 15561461
TI  - The effects of chronic nicotine and alcohol use on neurocognitive function.
AB  - Despite the extensive literatures on the independent effects of chronic nicotine
      and alcohol use on neurocognition, little is known about their combined impact.
      The purpose of this paper was to examine the effects of chronic nicotine and
      alcohol use on neurocognition in participants who took part in Project MATCH, a
      study of the efficacies of three behavioral treatments for adults diagnosed with
      alcohol abuse or dependence. Multiple regression and ANCOVA analyses were
      conducted to determine the relationship between lifetime weeks of tobacco use and
      years of alcohol use problems and neuropsychological test performance. Results
      showed that although years of chronic alcohol use was significantly inversely
      related to neuropsychological test scores, and chronic nicotine use showed an
      additive effect, substance use accounted for little variance in
      neuropsychological functioning. These findings suggest that some protective
      factors may have helped to attenuate the impact of chronic substance use on
      neurocognition. The importance of considering individual differences in such
      research is highlighted. Additional studies on the combined effects of chronic
      nicotine and alcohol use on neuropsychological function are warranted.

PMID- 15561462
TI  - Impact factor rises again.

PMID- 15561463
TI  - Partial behavioral compensation is revealed in balance tasked mutant mice lacking
      otoconia.
AB  - We describe for the first time behavioral tests which show that mammals with
      congenital absence of otoconia can learn a motor task that normally relies on
      gravity perception. The mouse mutation tilted (tlt) occurs in the otopetrin 1
      gene (Otop1(tlt/tlt)) and eliminates an essential component necessary for the
      formation of otoconia. Our data show that even in the absence of otoconia, tlt
      mutant mice, like normal mice, learn to cross a bar suspended between two boxes
      and, with practice, improve their speed of crossing. Despite this learned
      compensatory skills, tlt mutant mice show balance impairments, such as falling
      from the bar, not observed in wild type (WT) or heterozygous (het) Otop1(+/)(tlt)
      littermates. The tlt mutant mice also use their tail as additional support, a
      behavior that is rarely exhibited in the control littermates. Interestingly, the
      Otop1(+/)(tlt) heterozygous littermates show in many aspects an intermediate
      phenotype between wild type and tlt mutant mice, suggestive of a gene dosage
      effect. Overall, these data support the notion that mammals can use other otic
      and extraotic receptors such as semicircular canals and limb proprioreceptors,
      respectively, to compensate for the absence of otoconia-mediated gravity
      perception in a balance task.

PMID- 15561464
TI  - Chronic stress and social housing differentially affect neurogenesis in male and
      female rats.
AB  - Stress plays an important role in the development of affective disorders. Women
      show a higher prevalence for these disorders than men. The course of a depression
      is thought to be positively influenced by social support. We have used a chronic
      stress model in which rats received foot-shocks daily for 3 weeks. Since rats are
      social animals we hypothesised that 'social support' might reduce the adverse
      effects of chronic stress. To test this hypothesis, male and female rats were
      housed individually or socially in unisex groups of four rats. The proliferation
      marker bromodeoxyuridine (BrdU) was injected 2 weeks before the sacrifice to
      investigate if stress and social housing influenced the survival of proliferating
      cells in the dentate gyrus (DG). To investigate changes in proliferation, another
      group of rats was sacrificed the day after the last BrdU injection. Stress
      significantly decreased BrdU labelling in individually housed males and not
      significantly in socially housed males. In individually housed females stress
      increased BrdU labelling, which was prevented by social housing. The increase
      found in females is most likely caused by differences in survival rate, since
      cell proliferation was not affected by stress or housing conditions. These
      results indicate that social support can affect neurogenesis in both female and
      male rats, however in a different way.

PMID- 15561465
TI  - Role of nicotinic acetylcholine receptors in the regulation of kainic acid
      induced hippocampal cell death in mice.
AB  - Kainic acid (KA) is a well-known excitatory, neurotoxic substance. In mice,
      morphological damage of hippocampus induced by KA administered
      intracerebroventricularly (i.c.v.) was markedly concentrated on the CA3 pyramidal
      neurons. In the present study, the possible role of nicotinic acetylcholine
      receptors (nAchRs) in hippocampal cell death induced by KA (0.1 microg)
      administered i.c.v. was examined. Methyllycaconitine (MC; nAchRs antagonist, 20
      microg) attenuated KA-induced CA3 pyramidal cell death. KA increased
      immunoreactivities (IRs) of phorylated extracellular signal-regulated kinase (p
      ERK; at 30 min), p-CaMK II (at 30 min), c-Fos (at 2 h), c-Jun (at 2 h), glial
      fibrillary acidic protein (GFAP at 1 day), and the complement receptor type 3 (OX
      42; at 1 day) in hippocampal area. MC attenuated selectively KA-induced p-CaMK
      II, GFAP and OX-42 IR in the hippocampal CA3 region. Our results suggest that p
      CaMK II may play as an important regulator responsible for the hippocampal cell
      death induced by KA administered i.c.v. in mice. Reactive astrocytes, which was
      meant by GFAP IR, and activated microglia, which was meant by OX-42 IR, may be a
      good indicator for measuring the cell death in hippocampal regions by KA-induced
      excitotoxicity. Furthermore, it is implicated that niconitic receptors appear to
      be involved in hippocampal CA3 pyramidal cell death induced by KA administered
      i.c.v. in mice.

PMID- 15561466
TI  - Influence of sweet tasting solutions on opioid withdrawal.
AB  - The effect of the ingestion of palatable fluids on the suppression of opioid
      withdrawals in the opioid-dependent rats was studied. Physical dependence was
      induced by administration of morphine over a period of 6 days. Withdrawals were
      precipitated with naloxone (1 mg/kg, s.c.) 4 h after the last morphine injection
      on the 6th day. Test drugs (10-30% sucrose solution) were given orally for 2 h
      prior to naloxone-induced withdrawal in 14 h water deprived rats. Somatic signs
      of withdrawals were scored by using the global Gellert-Holtzman rating scale.
      Animals pretreated with low doses of sucrose solution (10-15%) did not produce
      any effect on the global withdrawal scale whereas a significant decrease on the
      global withdrawal scores was observed at higher doses of sucrose solution (20
      30%) as compared to the controls. All the individual behavioral signs of
      withdrawals were significantly suppressed in a dose-related manner at higher
      doses of sucrose solutions whereas minimal suppression was observed for facial
      fasciculation/teeth chattering. These findings provide support that ingestion of
      high concentrations of sucrose solutions for shorter duration may activate the
      endogenous opioid system and appears to have an important role in modifying
      morphine withdrawals.

PMID- 15561467
TI  - Supraspinal and systemic administration of the nicotinic-cholinergic agonist (+/
      )-epibatidine has inhibitory effects on C-fiber reflexes in the rat.
AB  - This study assessed the effects of the nicotinic agonist (+/-)-epibatidine (EPIB)
      on the C-fiber flexor reflex in the anesthetized rat. Electrical stimulation of
      the hindpaw produces a long latency (> 150 ms) C-fiber mediated electromyographic
      (EMG) burst in hindlimb flexor muscles. EPIB (0.01, 0.03 micromol/kg, i.p.)
      significantly reduced (p < 0.05) C-fiber -related EMG activity by 46 and 64%,
      respectively. This effect was similar to that produced by the opioid morphine
      (21.0 micromol/kg, i.p.) and the NMDA receptor antagonist MK-801 (3.0
      micromol/kg, i.p.). Nicotinic receptor blockade with the antagonists mecamylamine
      (5.0 micromol/kg, i.p.) and chlorisondamine (23.0 nmol/rat,
      intracerebroventricular) attenuated the effects of systemic EPIB on the C-fiber
      reflex. EPIB injection (0.04 nmol/rat) into the nucleus raphe magnus
      significantly decreased C-fiber EMG activity by 67%, suggesting a supraspinal
      site of action. In contrast, EPIB (0.6 nmol/rat) administered into the lumbar
      spinal cord significantly increased the C-fiber reflex by 117%. In summary,
      systemic and supraspinal EPIB exerted an inhibitory effect on central pain
      transmitting pathways, while a stimulatory effect is elicited in the spinal cord.
      The inhibitory effects are consistent with the reported analgesic properties of
      EPIB. The excitatory effect may be related to the reported algogenic responses
      when EPIB is administered intrathecally.

PMID- 15561468
TI  - Effects of topiramate on oral dyskinesia induced by reserpine.
AB  - Recently, we have described the antidyskinetic property of the GABA mimetic drug
      valproic acid on reserpine-induced oral dyskinesia, an animal model that has been
      related to tardive as well as acute dyskinesias, which are associated with
      important neuropathologies. The present study investigates the effects of
      different doses of the GABA mimetic anticonvulsant topiramate on the
      manifestation of reserpine-induced orofacial dyskinesia. Female EPM-M1 mice
      received two injections of control solution or of 0.5 mg/kg reserpine separated
      by 48 h. Twenty-four hours after the second reserpine or control solution
      injection, animals were acutely treated with control solution or topiramate (1,
      3, 10 or 30 mg/kg) and were observed for quantification of oral dyskinesia or
      general activity in an open-field. In order to verify the effects of topiramate
      per se on oral dyskinesia or general activity, female EPM-M1 mice were acutely
      treated with control solution or 1, 3, 10 or 30 mg/kg topiramate and observed for
      quantification of oral dyskinesia and general activity. The highest dose of
      topiramate completely abolished the manifestation of reserpine-induced oral
      dyskinesia whereas the doses of 3 and 10 mg/kg significantly attenuated it. None
      of the doses of the anticonvulsant modified spontaneous locomotion frequency or
      oral movements, whereas spontaneous rearing frequency was decreased by 3, 10 and
      30 mg/kg topiramate. The highest dose of topiramate did not modify general
      activity in reserpine-treated mice. These results support the potential
      therapeutic use of topiramate in the treatment of oral dyskinesias.

PMID- 15561469
TI  - Effects of age on reserpine-induced orofacial dyskinesia and possible protection
      of diphenyl diselenide.
AB  - Acute reserpine administration produces persistent oral dyskinesia in rats, an
      alleged animal model of tardive dyskinesia. The pathophysiology of the syndrome
      remains unclear, but experimental evidence suggests that neurodegeneration in the
      basal ganglia caused by oxidative stress plays a pivotal role in TD development.
      In this paper, the authors examined whether diphenyl diselenide, an
      organochalcogen with antioxidant properties, changes the behavioral and
      neurochemical effect of acute reserpine administration in old rats. The basal
      vacuous chewing movements (VCMs) and facial twitching (FT) duration was higher in
      old rats (15 months of age), when compared with adult rats (3 months of age;
      0.01). Basal thiobarbituric acid-reactive species (TBARS) levels were increased
      only in the cortex of old rats, when compared to adult animals (p < .05).
      Reserpine injection (1mg/kg, s.c. for 3 days every other day) caused a
      significant increase on the tongue protusion (TP) frequency (p < .01) and facial
      twitching duration (p < .01) in old rats. Diphenyl diselenide (10 mg/kg, i.p. for
      4 days, starting the day before reserpine) reversed only reserpine-induced TP
      increase (p < .01). Reserpine caused a significant increase in striatal TBARS
      levels (p < .01) and diselenide reversed (p < .01) the effect of reserpine on
      TBARS levels in the striatum. In subcortical parts, isolated reserpine or
      diselenide administration significantly increased (p < .01) the levels of TBARS,
      while simultaneous treatment with reserpine and diselenide reverted this effect
      (p < .01). The results of the present study confirmed the effects of age on
      orofacial dyskinesia. Diphenyl diselenide, an organochalcogen with antioxidant
      properties, showed modest effects on reserpine-induced orofacial dyskinesia.
      However, additional studies are still necessary to establish whether this
      compound can be considered an effective antioxidant in other models of
      neurotoxicity.

PMID- 15561470
TI  - Rapid differentiation of NT2 cells in Sertoli-NT2 cell tissue constructs grown in
      the rotating wall bioreactor.
AB  - Cell replacement therapy is of great interest as a long-term treatment of
      neurodegenerative diseases such as Parkinson's disease (PD). We have previously
      shown that Sertoli cells (SC) provide neurotrophic support to transplants of
      dopaminergic fetal neurons and NT2N neurons, derived from the human clonal
      precursors cell line NTera2/D1 (NT2), which differentiate into dopaminergic NT2N
      neurons when exposed to retinoic acid. We have created SC-NT2 cell tissue
      constructs cultured in the high aspect ratio vessel (HARV) rotating wall
      bioreactor. Sertoli cells, NT2, and SC plus NT2 cells combined in starting ratios
      of 1:1, 1:2, 1:4 and 1:8 were cultured in the HARV in DMEM with 10% fetal bovine
      serum and 1% growth factor reduced Matrigel for 3 days, without retinoic acid.
      Conventional, non-HARV, cultures grown in the same culture medium were used as
      controls. The presence of tyrosine hydroxylase (TH) was assessed in all culture
      conditions. Sertoli-neuron-aggregated-cell (SNAC) tissue constructs grown at
      starting ratios of 1:1 to 1:4 contained a significant amount of TH after 3 days
      of culture in the HARV. No TH was detected in SC HARV cultures, or SC, NT2 or SC
      NT2 conventional co-cultures. Quantitative stereology of immunolabled 1:4 SNAC
      revealed that approximately 9% of NT2 cells differentiate into TH-positive (TH+)
      NT2N neurons after 3 days of culture in the HARV, without retinoic acid. SNAC
      tissue constructs also released dopamine (DA) when stimulated with KCl,
      suggesting that TH-positive NT2N neurons in the SNAC adopted a functional
      dopaminergic phenotype. SNAC tissue constructs may be an important source of
      dopaminergic neurons for neuronal transplantation.

PMID- 15561471
TI  - Gastric antisecretory effects of synthetic cannabinoids after central or
      peripheral administration in the rat.
AB  - Previous studies have revealed that cannabinoid (CB)-receptor agonists inhibit
      gastric acid secretion stimulated by indirectly acting agents, but not by
      histamine. Aiming to investigate whether central or peripheral mechanisms are
      involved, the effects of the synthetic CB-receptor agonists WIN55,212-2 and HU
      210, administered either intracerebroventricularly (i.c.v.) or intravenously
      (i.v.) to the anaesthetized rat with lumen-perfused stomach, against gastric acid
      secretion induced by pentagastrin were tested. Injected i.c.v., both WIN55,212-2
      (50 and 100 microg/kg) and HU-210 (25, 50 and 100 microg/kg) were ineffective on
      either basal secretion or acid output induced by pentagastrin (7.7 microg/kg,
      i.v.). By contrast, i.v. injections of WIN55,212-2 (100 and 1000 microg/kg) or HU
      210 (10-100 microg/kg) significantly inhibited pentagastrin-induced acid
      secretion, maximal reductions being 75.70 and 82.24% for WIN55,212-2 and HU-210,
      respectively. The gastric antisecretory effect of HU-210 was prevented by
      administration of the selective CB(1)-receptor antagonist SR141716A (1000
      microg/kg, i.v.). These results show that CB(1)-receptors mediating inhibition of
      gastric acid secretion in the rat are mainly peripherally located.

PMID- 15561472
TI  - Accelerometric measurement of involuntary movements during pallidal deep brain
      stimulation of patients with generalized dystonia.
AB  - Accelerometric activity during rest and posture was quantified in the upper
      dominant limb of 14 patients with primary or secondary dystonia and five healthy
      control subjects. Data were recorded before and after bilateral implantation of
      the stimulating electrodes in the Globus Pallidus internus. Clinical evaluation
      was based on the Burke-Marsden-Fahn's Dystonia Rating Scale (BMFDRS). For the
      patient group, I(t), the integral (i.e. area) of the acceleration power spectrum
      over the total frequency range (0.6-16 Hz) decreased as the clinical state of the
      patients improved following deep brain stimulation (p < 0.01) during rest and
      posture. Ten days after surgery, there were no I(t) differences between control
      subjects and patients (p > 0.05). A significant correlation was found between the
      global BMFDRS scores and I(t) for rest (p < 0.01) but not for posture. No
      significant correlation was found between I(t) and a partial BMFDRS score for the
      right arm for rest or posture. The integral I(t) provides a valid indicator of
      the motor activity generated by the arm of the patient but further analyses are
      needed to monitor patients' progress not only during their hospitalization but
      also after they are released from the hospital, and to understand why this
      measure does not correlate with partial BMFDRS scores.

PMID- 15561473
TI  - Racial differences in trajectories of cigarette use.
AB  - This study examined racial differences in developmental trajectories of cigarette
      smoking from childhood into young adulthood. We used data from the Pittsburgh
      Youth Study, a prospective, longitudinal study of high-risk males. We developed
      trajectories of cigarette smoking from age 10 through age 25. Models were
      estimated separately for African-Americans (N = 562) and Whites (N = 421) because
      preliminary analyses indicated that there were significant racial differences in
      onset, levels and patterns of cigarette use. Three trajectory groups emerged for
      both races: nonsmokers, light/occasional smokers and heavy/regular smokers.
      Significantly more Whites were in the heavy/regular smoker group and more African
      Americans were in the nonsmoker group. White compared to African-American
      heavy/regular smokers began smoking earlier and reached higher mean quantities of
      cigarettes per day. In addition, there were racial differences in the timing and
      rapidity of the development of regular smoking over time. Race remained a
      significant predictor of cigarette use even after controls for socioeconomic
      status. Overall, the results indicate that developmental trends in smoking differ
      by race and that cigarette smoking remains more prevalent and more frequent for
      White than African-American males, at least through young adulthood.

PMID- 15561474
TI  - HIV risk behaviors and alcohol intoxication among injection drug users in Puerto
      Rico.
AB  - This paper reports results of an analysis of the association between alcohol
      intoxication and injection and sexual HIV risk behaviors among 557 Hispanic
      heroin and cocaine injectors, not in treatment, who were recruited in poor
      communities in Puerto Rico. Subjects were part of a longitudinal prevention
      intervention study aimed at reducing drug use and HIV risk behaviors.
      Participants reported a high prevalence of co-occurring conditions, particularly
      symptoms of severe depression (52%) and severe anxiety (37%), measured by Beck's
      Depression Index and Beck's Anxiety Index, respectively. Alcohol intoxication
      during the last 30 days was reported by 18% of participants. Associations were
      found between alcohol intoxication and both injection and sexual risk behaviors.
      In the bivariate analysis, subjects reporting alcohol intoxication were more
      likely to inject three or more times per day, pool money to buy drugs, share
      needles, and share cotton. They were also significantly more likely to have a
      casual or paying sex partner and to have unprotected sex with these partners.
      After adjustment, sharing needles and cotton, having sex with a paying partner or
      casual partner, and exchanging sex for money or drugs were significantly related
      to alcohol intoxication. HIV prevention programs, to be effective, must address
      alcohol intoxication and its relation to injection and sexual risk behaviors as a
      central issue in HIV prevention among drug injectors.

PMID- 15561475
TI  - How much do Manhattan-arrestees spend on drugs?
AB  - INTRODUCTION: Information about individuals' drug expenses can indicate much
      about the size of drug markets, the financial burden of use, drug-related crime,
      and potential challenges for treatment. Most often, expenses have been estimated
      holistically by asking respondents to report how much they spent. In 2000, the
      Arrestee Drug Abuse Monitoring (ADAM) program introduced an advanced
      questionnaire using a series of highly specific questions like, "how much cash
      did you pay for crack that last time you bought it?" METHODS: This paper
      describes a procedure for estimating arrestees' drug expenses with the new ADAM
      questionnaire, discusses pitfalls in interpretation, presents findings for 2979
      ADAM-Manhattan respondents interviewed 2000-2002, examines covariates of drug
      expense, and compares the 2000-2002 findings with those obtained from 2256
      respondents interviewed 1998-1999 with the previous questionnaire. RESULTS: Among
      2000-2002 arrestees, median drug expense in the past 30 days varied widely with
      frequency of use and drug-user type. Infrequent marijuana-only users spent as
      little as $5, daily marijuana-only users spent about $600. Arrestees that used
      both heroin and cocaine spent over $1000. Estimates with the 1998-1999 data were
      about half as large. DISCUSSION: ADAM's new drug market questions may greatly
      advance the quality of estimates of drug expenses. However, further research is
      needed to better establish the estimator's accuracy.

PMID- 15561476
TI  - Shaping smoking cessation using percentile schedules.
AB  - Behavioral interventions that provide incentives contingent upon abstinence are
      effective addiction treatments. Nevertheless, these treatments often fail for
      individuals whose recent behaviors are very different from those reinforced.
      These hard-to-treat individuals may require shaping to achieve abstinence. We
      used percentile schedules to shape smokers' delivery of breath samples indicative
      of recent smoking abstinence (breath carbon monoxide (BCO) <4 ppm). Percentile
      schedules deliver incentives to current behaviors proximal to the target.
      Participants (N = 102) were assigned to treatments delivering incentives for
      breath COs at or below the 10th, 30th, 50th, or 70th percentile of recent breath
      COs. Each condition effectively ensured contact with available contingencies, and
      resulted in BCO <4 ppm in >90% of the 30th, 50th and 70th percentile groups
      versus 63% in the 10th percentile. The 30th, 50th and 70th percentiles were
      especially effective in a sub-sample of hard-to-treat participants who did not
      deliver a breath CO <4 ppm during an initial abstinence test or during a nine
      visit baseline period, suggesting the value of shaping for this important sub
      sample.

PMID- 15561477
TI  - Neurophysiology of motor function following cannabis discontinuation in chronic
      cannabis smokers: an fMRI study.
AB  - The objective of this study was to identify the differences in cerebral
      activation between chronic cannabis smokers and controls in response to finger
      sequencing. We hypothesized that attentional areas related to motor function as
      well as primary and supplementary motor cortices would show diminished activation
      in chronic cannabis smokers. Nine cannabis smokers and 16 controls were included
      in these analyses. Scanning was performed on a GE 1.5T scanner. Echo planar
      images and high-resolution MR images were acquired. The challenge paradigm
      included left and right finger sequencing. Group differences in cerebral
      activation were examined for Brodmann areas (BA) 4, 6, 24, and 32 using ROI
      analyses in SPM. Cannabis users, tested within 4-36 h of discontinuation,
      exhibited significantly less activation than controls in BA 24 and 32 bilaterally
      during right- and left-sided sequencing and for BA 6 in all tasks except for left
      sided sequencing in the left hemisphere. There were no statistically significant
      differences for BA 4. None of these regional activations correlated with urinary
      cannabis concentration and verbal IQ for smokers. These results suggest that
      recently abstinent chronic cannabis smokers produce reduced activation in motor
      cortical areas in response to finger sequencing compared to controls.

PMID- 15561478
TI  - Alcohol use among university students in Lebanon: prevalence, trends and
      covariates. The IDRAC University Substance Use Monitoring Study (1991 and 1999).
AB  - The practical inexistence of research on alcohol use among university students in
      Lebanon and other Arab countries spurred us at IDRAC to initiate a university
      based substance use monitoring study, so far conducted in two phases (1991 and
      1999), to assess the prevalence, patterns, trends, and factors associated with
      the use and abuse of alcohol (and other substances). In both phases, the sample
      was a stratified cluster, representing 25% (N = 1850) of the student population
      of two major universities in Lebanon. The rates of lifetime alcohol use and
      problem use have increased from 1991 to 1999, the increase being higher in
      younger cohorts and in females. Belief in God and practice of that belief,
      irrespective of the students' religion, were associated with less frequent
      experimentation with alcohol. Although more Christians ever drank alcohol, once
      users, university students (irrespective of their religion) had the same rates of
      alcohol problem use and dependence. Several other covariates concordant with the
      international literature were also delineated such as students' anti-social
      behavior, and family and peer environment.

PMID- 15561479
TI  - Smoking, nicotine dependence and psychiatric comorbidity--a population-based
      study including smoking cessation after three years.
AB  - BACKGROUND: Evidence suggests that nicotine-dependent smokers are at increased
      risk for psychiatric comorbidity but general population data that included the
      number of nicotine dependence and withdrawal symptoms according to DSM-IV, the
      Fagerstrom Test for Nicotine Dependence (FTND), somatoform disorders and the
      number of psychiatric diagnoses are rare. The goal of the present study was to
      analyse relationships of smoking and nicotine dependence with psychiatric disease
      and whether psychiatric disease predicts the sustaining of smoking after three
      years. METHODS: Cohort study with a random adult population sample in a northern
      German region (N = 4075) including a baseline measurement of ever daily smokers
      aged 18-64 (n = 2458), a first follow-up of the current smokers at baseline (n =
      1552) after 30 months and a second follow-up after 36 months. Measures included
      DSM-IV diagnoses by the Composite International Diagnostic Interview, FTND,
      smoking cessation by interview. RESULTS: Current daily smokers showed higher odds
      of a substance use disorder other than nicotine dependence compared with never
      smokers (odds ratio, OR, 4.6; confidence interval, CI, 2.9-7.2), affective (OR
      1.8; CI 1.4-2.5), anxiety (OR 1.6; CI 1.2-2.0) or somatoform disorder (OR 1.4; CI
      1.0-1.8). DSM-IV nicotine dependence and the FTND were positively related with
      the number of psychiatric diagnoses. Psychiatric comorbidity did not predict the
      maintenance of smoking or quitting. CONCLUSIONS: Findings of increased rates of
      mental disorders among smokers and nicotine-dependent smokers in the adult
      general population are supported by this study. The number of nicotine dependence
      and withdrawal symptoms are related to mental disorders. In addition, somatoform
      disorders show relationships with smoking similar to relationships with
      depressive or anxiety disorders. The intention to stop smoking should be
      proactively supported among these comorbid patients.

PMID- 15561480
TI  - The acute and sub-acute effects of 'ecstasy' (MDMA) on processing of facial
      expressions: preliminary findings.
AB  - RATIONALE: There is evidence that serotonergic processes may modulate the
      processing of fearful facial expressions. It is therefore possible that the
      recreational drug 'ecstasy' (MDMA), which has marked serotonergic effects, may
      affect people's ability to recognise human facial expressions portraying fear.
      OBJECTIVE: The present study therefore aimed to determine whether ecstasy users
      differed from controls in fear recognition at two time points: shortly after
      taking the drug and a few days later. METHODS: Sixteen ecstasy users and 21
      controls were compared on a facial expression recognition task involving the 6
      basic emotions (happiness, surprise, sadness, anger, fear and disgust) and on
      self-ratings of mood on the night of drug use (day 0) and 4 days later (day 4).
      RESULTS: In recognising fearful facial expressions, ecstasy users were more
      accurate than controls on day 0 but less accurate than them on day 4 when
      compared with their overall ability to recognise other basic emotions. Accuracy
      of fear recognition on day 4 was negatively correlated with both years of ecstasy
      use and number of ecstasy tablets taken on a typical session. On self-rated
      aggression scales, ecstasy users scored lower than controls on day 0 and higher
      on day 4. CONCLUSIONS: These results support the notion that 5-HT plays a role in
      modulating the recognition of fearful facial expressions. Increased accuracy of
      fear recognition may relate to 5-HT release following ecstasy use on day 0, and
      decreased accuracy may reflect subsequent depletion of 5-HT mid-week.

PMID- 15561481
TI  - Recognition of a dopamine replacement therapy dependence syndrome in Parkinson's
      disease: a pilot study.
AB  - Patients with Parkinson's disease may use Dopamine Replacement Therapy (DRT) in
      excess of therapeutic need. We investigate whether a group of 10 patients with
      Parkinson's disease, provisionally diagnosed with "Hedonistic Homeostatic
      Dysregulation" because of their excessive use of DRT, met established operational
      psychiatric criteria for substance dependence, compared with 10 patients with
      Parkinson's disease compliant with prescribed DRT. Using a semi-structured
      questionnaire designed to distinguish between adaptive therapeutic dependence on
      DRT and a maladaptive pathological pattern of DRT use, in conjunction with the
      SCID-1, we found that seven of the patients deemed by their treating physicians
      to be misusing DRT fulfilled operational criteria for maladaptive dependence in
      contrast to none of the compliant group. The majority experienced dysphoric
      "withdrawal" symptoms in the "off" state and increased their dose of DRT in an
      effort to control their mood. They also continued to use high doses of DRT
      despite disabling dyskinesias and social difficulties. This study provides
      preliminary evidence that some patients with Parkinson's disease may become
      maladaptively dependent on DRT. This finding has both clinical relevance for the
      treatment of PD and further implicates dopaminergic pathways in the genesis of
      substance dependence.

PMID- 15561482
TI  - Preliminary evidence of an association between childhood abuse and cannabis
      dependence among African American first-episode schizophrenia-spectrum disorder
      patients.
AB  - Cannabis dependence is a prevalent comorbid substance use disorder among patients
      early in the course of a schizophrenia-spectrum disorder. Determining risk
      factors for substance abuse may be helpful in designing interventions to reduce
      the psychosocial morbidity associated with substance abuse among this population.
      This study aimed to determine whether or not African American, socially
      disadvantaged, first-episode schizophrenia-spectrum patients with cannabis
      dependence experienced greater levels of childhood abuse and neglect compared to
      similar patients without comorbid cannabis dependence. Among 29 eligible
      patients, 18 participated in this pilot study. First-episode patients with
      comorbid cannabis dependence (n = 8) reported significantly greater childhood
      physical and sexual abuse compared to those without comorbid cannabis dependence
      (n = 10). This represents preliminary evidence of an association between
      childhood maltreatment and cannabis dependence among this especially vulnerable
      population. Childhood physical and sexual abuse may be a risk factor for the
      initiation of cannabis dependence and other substance use disorders in the early
      course of schizophrenia.

PMID- 15561483
TI  - A tube-fed liquid formula diet containing dietary fiber increased stool weight in
      bed-ridden elderly patients.
AB  - OBJECTIVE: The number of bedridden elderly patients who need a liquid diet has
      been increasing. We evaluated the usefulness of a tube-fed liquid diet containing
      cellulose and oligosaccharide for elderly bedridden patients. METHODS: Twenty-two
      elderly bedridden patients were given a liquid diet containing cellulose and
      lafinose for 4 wk. Parameters associated with blood and stool weight were
      measured during this period. RESULTS: Stool weight increased by 32.0 g in men and
      8.8 g in women at 2 wk and remained at these weights up to 4 wk (P < 0.05 before
      and after 2 wk, 3 wk, and 4 wk in men, and P < 0.05 before and after 3 wk in
      women). Body weight increased in men (0.5 kg) and women (0.7 kg) 15 d after
      starting the diet and then remained at these values up to 29 d thereafter, and
      statistically significant differences were not seen. There were no changes in
      nutritional parameters such as total protein. CONCLUSION: No significant changes
      were observed in the general condition of elderly patients, with the exception of
      a positive increase in fecal weight, by 30-d supplementation of a liquid diet
      containing cellulose and lafinose.

PMID- 15561484
TI  - Postgastrectomy polyneuropathy with thiamine deficiency is identical to beriberi
      neuropathy.
AB  - OBJECTIVE: We assessed whether postgastrectomy polyneuropathy associated with
      thiamine deficiency is clinicopathologically identical to beriberi neuropathy,
      including a biochemical determination of thiamine status. METHODS:
      Clinicopathologic features of 17 patients who had postgastrectomy polyneuropathy
      with thiamine deficiency were compared with those of 11 patients who had thiamine
      deficiency neuropathy caused by dietary imbalance. RESULTS: The typical
      presentation for the two etiologies was as a symmetric sensorimotor
      polyneuropathy predominantly involving the lower limbs. A variety of clinical
      features, including neuropathic symptoms, progression, and coexistence of heart
      failure or Wernicke's encephalopathy, was seen similarly in both conditions. In
      both groups, the main electrophysiologic findings were those of axonal
      neuropathy, most prominently in the lower limbs. Sural nerve biopsy specimens
      also indicated axonal degeneration in both groups. Subperineurial edema was
      commonly observed. CONCLUSION: This study showed that thiamine-deficiency
      neuropathies due to gastrectomy and dietary imbalance are identical despite
      variability in their clinicopathologic features and suggested that thiamine
      deficiency can be a major cause of postgastrectomy polyneuropathy.

PMID- 15561485
TI  - Omega-3 fatty acids and selenium as coronary heart disease risk modifying factors
      in Asian Indian and Chinese males.
AB  - OBJECTIVE: Asian Indian men are reported to have a higher incidence of coronary
      heart disease than men of other ethnic groups worldwide. Among the many
      hypotheses, one possible risk factor may be related to their dietary habits. This
      study estimated the plasma concentrations of fatty acids, antioxidant vitamins,
      and selenium in Indians and Chinese of Singapore. METHODS: The study population
      consisted of 145 Indian men and 147 Chinese men ages 26 to 79 y from a cross
      sectional survey, the National University of Singapore Heart Study. RESULTS: Our
      findings indicated that Indians had lower plasma concentrations of docosahexanoic
      acid (3.07% versus 3.54%, P < 0.001), alpha-linolenic acid (0.48% versus 0.57%, P
      < 0.001), and total omega-3 fatty acids (4.71% versus 5.27%, P < 0.001) than did
      the Chinese. Arachidonic acid was higher in Indians (4.83%) than in the Chinese
      (4.51%, P = 0.007). The ratio of omega-3 acid to omega-6 fatty acid was also
      lower in Indians (0.15) than in the Chinese (0.16, P = 0.007). There were no
      significant differences in the concentrations of monounsaturated fatty acids, but
      saturated fatty acids were higher in Indians (39.17%) than in the Chinese
      (38.28%, P < 0.001). Analysis of vitamins A, C, and E showed no significant
      differences between Indians (0.67, 5.72, and 13.04 mg/L, respectively) and
      Chinese (0.68, 6.48, and 12.71 mg/L, respectively); however, serum concentration
      of selenium in Indians (117.49 microg/L) was significantly lower than in the
      Chinese (126.72 microg/L, P < 0.001). CONCLUSION: The results suggest that lower
      plasma concentrations of omega-3 fatty acids and selenium and higher
      concentrations of arachidonic acid and saturated fatty acids in Indians may
      reflect lower intakes of marine foods and, as a consequence, higher
      susceptibility to coronary heart disease.

PMID- 15561486
TI  - Methylenetetrahydrofolate reductase polymorphism determines the plasma
      homocysteine-lowering effect of large-dose folic acid supplementation in patients
      with cardiovascular disease.
AB  - OBJECTIVE: The polymorphism of the gene encoding methylenetetrahydrofolate
      reductase (MTHFR) and folic acid nutritional status play important roles in
      atherosclerosis. The present study investigated the total homocysteine-lowering
      effect of folic acid in response to the MTHFR genotype in patients who have
      cardiovascular disease. METHODS: Twenty-three patients who had cardiovascular
      disease (ages 44 to 88 y) were supplemented with 5 mg of folic acid/d for 8 wk.
      Blood samples were collected before and after supplementation for the measurement
      of folic acid. The presence of the 677C-->T mutation was assessed by polymerase
      chain reaction followed by restriction enzyme analysis. RESULTS: After the 8 wk
      of folic acid supplementation, plasma total homocysteine decreased 40% in
      patients who had the TT genotype, 23% in those who had the CT genotype, 10% in
      those who had the CC genotype, and 27% in carriers of the T allele. The plasma
      total homocysteine-lowering effect of folic acid was significant only in patients
      who had the CT genotype and in carriers of the T allele. CONCLUSIONS: The MTHFR
      polymorphism may be involved in the total homocysteine-lowering effect of folic
      acid in patients who have cardiovascular disease.

PMID- 15561487
TI  - Bioavailability of cellobiose by tolerance test and breath hydrogen excretion in
      humans.
AB  - OBJECTIVE: Prebiotic substances have the property of intestinal fermentation.
      Cellobiose has a beta-1,4 linkage, so it is resistant to hydrolysis by human
      small intestinal disaccharidase and, hence, reaches the colon undigested. Until
      this study, it was unclear whether cellobiose has fermentability or
      bioavailability. The objectives of this study were to clarify whether cellobiose
      is fermented in the large intestine and to estimate the available energy from
      cellobiose intake by using tolerance tests and breath hydrogen tests in healthy
      female subjects. METHODS: Ten healthy young women (20.5 +/- 2.1 y) who did not
      develop diarrhea after ingesting 30 g of cellobiose in a previous experiment were
      recruited. Tolerance tests and breath hydrogen tests for 25 g of cellobiose or
      glucose were carried out at least 2 wk apart. Blood samples were collected before
      and at 30-min intervals up to 3 h after ingestion. Breath gas samples were
      collected simultaneously before and at 30-min intervals up to 6 h after ingestion
      of cellobiose or glucose. Blood glucose and insulin levels and the concentration
      of breath hydrogen were analyzed. RESULTS: When 25 g of cellobiose was ingested,
      there was no increase in blood glucose or insulin secretion, but these markers
      increased remarkably with glucose ingestion. The excretion of breath hydrogen gas
      after cellobiose ingestion was significantly greater than that after glucose
      ingestion. CONCLUSIONS: Orally ingested cellobiose was well fermented in human
      large intestine, and its available energy was estimated to be about 2 kcal/g.

PMID- 15561488
TI  - Ethanol washing does not attenuate the hypocholesterolemic potential of soy
      protein.
AB  - OBJECTIVE: A feeding study in rats investigated the principal active component
      for the hypocholesterolemic effect of soy protein isolate (SPI) by comparing the
      effect before and after ethanol washing. METHODS: Five-week-old male Sprague
      Dawley rats were fed cholesterol-enriched AIN-93G diets containing 20% casein
      (CAS), 20% SPI, 20% ethanol-washed SPI (EWS), 18.4% EWS plus 1.6% ethanol extract
      (EE), or 20% CAS plus 1.6% EE for 2 wk. RESULTS: Plasma cholesterol
      concentrations in rats fed EWS and SPI were comparable and were significantly
      lower than those in rats fed CAS. The addition of EE to EWS and CAS did not
      influence plasma cholesterol level. Fecal steroid excretion of the three SPI
      groups was higher than that of the two CAS groups. The addition of EE to EWS and
      CAS showed a tendency to increase acidic steroid and decrease neutral steroid.
      CONCLUSIONS: In this experiment which used identifiable protein preparations, a
      significant fraction of the cholesterol-lowering effect of SPI in rats was
      attributed to its protein component but not to the ethanol-extractable minor
      constituents including isoflavones.

PMID- 15561489
TI  - Histidine supplementation suppresses food intake and fat accumulation in rats.
AB  - OBJECTIVE: Histamine, a derivative of histidine, decreases food intake and body
      fat by activation of histamine neurons. Our objective was to clarify the effect
      of dietary histidine, in particular, on food intake and/or body fat accumulation
      in rats. METHODS: Male Wistar rats were assigned to one of four groups after
      acclimation and allowed free access to diets containing 20% casein (0%
      histidine), 20% casein plus 1.0% histidine, 20% casein plus 2.5% histidine, or
      20% casein plus 5% histidine for 8 d. RESULTS: Food intake and body weight were
      recorded daily and compared between groups. During the experimental period, food
      intake decreased according to the increases in dietary histidine. There was a
      negative and significant (P < 0.01) correlation between dietary histidine (grams
      per 8 d) and retroperitoneal fat pad (grams per 100 g of body weight). Uncoupling
      protein-1 mRNA in brown adipose tissue increased with increases in dietary
      histidine. CONCLUSION: Our results indicate that dietary histidine suppresses
      food intake and fat accumulation in rats.

PMID- 15561490
TI  - Itaconate reduces visceral fat by inhibiting fructose 2,6-bisphosphate synthesis
      in rat liver.
AB  - OBJECTIVE: Itaconate is an analog of phosphoenolpyruvate, which is an inhibitor
      of fructose-6-phosphate 2-kinase (F6P2Kinase), an enzyme that synthesizes
      fructose 2,6-bisphosphate (F26BP). Carbohydrates ingested are preferentially used
      for glycogen synthesis in the liver and muscles, and excess carbohydrates are
      metabolized by glycolysis in the liver and used for fatty acid synthesis. We
      hypothesized that itaconate is incorporated into liver cells and suppresses fat
      synthesis by inhibiting liver glycolysis at the step of phosphofructokinase,
      which is activated by F26BP. METHODS: Rats were allowed to eat ad libitum for 3
      wk or, in separate experiments, to limit food intake by pair feeding. One group
      was given drinking water (control group) and the other group was given a 10 g/L
      itaconate solution (itaconate group). We measured body weight gain, visceral fat
      accumulation, and F6P2Kinase activity. RESULTS: Body weight gain in the itaconate
      group was lower than that in the control group (P < 0.05). In the dietary
      controlled rats, there was no difference in body weight increase between groups,
      but visceral fat content (P < 0.01), plasma free fatty acid, and triacylglycerol
      levels (P < 0.05) were lower in the itaconate group than in the control group.
      Further, itaconate decreased the F26BP level (P < 0.05) in vivo and partly
      inhibited rat liver-type F6P2Kinase in vitro. CONCLUSIONS: These results indicate
      that itaconate, which is a decarboxylate and resembles phosphoenolpyruvate, is
      incorporated into liver cells and suppresses glycolysis by decreasing the level
      of F26BP, resulting in decreased visceral fat.

PMID- 15561491
TI  - Effects of fiber intake on the blood pressure, lipids, and heart rate in Goto
      Kakizaki rats.
AB  - OBJECTIVE: The prevalence of hypertension in individuals with diabetes mellitus
      is higher than that in individuals without diabetes mellitus. High fiber intake
      decreases blood glucose and lipids levels. This study investigated the effects of
      cereal fiber intake on systolic and diastolic blood pressures in a rat model of
      type 2 diabetes mellitus. METHODS: Thirty male Goto Kakizaki rats were randomly
      assigned to one of three groups. Each group was fed a barley diet, a white rice
      diet, or cornstarch diet. The rats were pair fed for 16 wk. Systolic and
      diastolic blood pressures were measured once every 4 wk by the photoelectric
      oscillometric tail-cuff method without anesthesia. RESULTS: The barley diet
      significantly decreased systolic blood pressure from week 12 and decreased the
      plasma levels of total cholesterol, triacylglycerol, and low-density lipoprotein
      cholesterol. There were significant positive correlations between plasma lipids
      levels and systolic blood pressure. CONCLUSIONS: High fiber intake has beneficial
      effects on systolic blood pressure and blood lipids levels and suggests that
      fiber intake should be increased in individuals who have diabetes mellitus to
      prevent complications.

PMID- 15561492
TI  - Effect of conjugated linoleic acid isomers on insulin resistance and mRNA levels
      of genes regulating energy metabolism in high-fat-fed rats.
AB  - OBJECTIVE: We investigated the effects of specific conjugated linoleic acid (CLA)
      isomers on glucose metabolism and insulin resistance and on mRNA levels of genes
      important in glucose and lipid metabolism. METHODS: Sprague-Dawley rats were fed
      for 8 wk on a high-fat diet (45% kcal from fat) or one of three CLA-supplemented
      diets (1% CLA) containing differing isomers of CLA, including a mixture of CLAs
      (CLA mix), cis-9, trans-11-CLA (C9,T11-CLA), or trans-10, cis-12-CLA (T10,C12
      CLA). RESULTS: Compared with the high-fat group, all the CLA groups had enhanced
      glucose tolerance. Insulin resistance index was significantly lower in the CLA
      treated groups. No significant difference could be observed in the level of serum
      lipids between groups and in the activities of phosphoenolpyruvate carboxylase,
      glucose-6-phosphatase, and glucokinase. However, C9,T11-CLA and T10,C12-CLA
      significantly increased acyl coenzyme A oxidase mRNA in skeletal muscle. In
      addition, C9,T11-CLA increased hepatic acyl coenzyme A oxidase mRNA and skeletal
      muscle uncoupling protein-2 mRNA. The CLA mix showed intermediate effects on the
      levels of these genes. CONCLUSIONS: The addition of all types of CLA to Sprague
      Dawley rats fed a high-fat diet can decrease insulin resistance. Possible
      mechanisms are increased fat oxidation and energy expenditure by increasing acyl
      coenzyme A oxidase and uncoupling protein-2 mRNA in the liver and/or skeletal
      muscle.

PMID- 15561493
TI  - Failure to gain weight on long-term parenteral nutrition attributed to tri
      iodothyronine thyrotoxicosis.
AB  - We describe the case of a 49-y-old female patient on long-term parenteral
      nutrition after abdominal surgery who failed to gain weight despite nutritional
      provision in excess of theoretical requirements. On investigation, she was found
      to have a negative nitrogen balance (-5.9 g) and to have a tri-iodothyronine
      thyrotoxicosis but without many of the typical clinical features of
      hyperthyroidism. The patient also had mild hypercalcemia and hyperphosphatemia,
      which resolved fully after mobilization and treatment of the thyrotoxicosis. A
      derangement of the liver function tests was observed, which worsened
      progressively during parenteral nutrition but resolved promptly at its
      discontinuation. This case illustrates the importance of carrying out appropriate
      investigations including all thyroid function tests on patients who fail to gain
      weight on nutritional support.

PMID- 15561494
TI  - Lack of association between dyslipidemia and insulin resistance in HIV-infected
      persons treated with highly active antiretroviral therapy.
AB  - OBJECTIVE: Highly active antiretroviral therapy has been implicated in the
      development of metabolic toxicities, including insulin resistance. Because it is
      "clinically silent," insulin resistance is often undetected, thus precluding the
      initiation of treatments that may prevent progression to frank diabetes. Previous
      studies have documented associations between dyslipidemic profiles and insulin
      resistance in patients who do not have the human immunodeficiency virus (HIV).
      Therefore, we explored whether serum lipids, parameters that are routinely
      measured in patients who have HIV or the acquired immunodeficiency syndrome,
      could be used to facilitate the identification of insulin resistance in patients
      infected with HIV. METHODS: Thirty-three adult patients who had clinically stable
      HIV infection and treated with highly active antiretroviral therapy fasted
      overnight and underwent phlebotomy to measure the following parameters: insulin
      levels, blood glucose, triacylglycerols, high-density lipoprotein cholesterol,
      low-density lipoprotein cholesterol, and total cholesterol. RESULTS: Of the 33
      participants, 15 had dyslipidemia, defined according to Adult Treatment Panel
      (ATP) III criteria, and 18 did not have dyslipidemia. The two groups did not
      differ significantly with respect to mean fasting insulin levels (P = 0.68). Only
      two participants had insulin levels that were higher than the laboratory
      reference range. No significant correlations were found between fasting insulin
      levels and any lipid parameters. CONCLUSIONS: Serum lipids are not predictive of
      fasting insulin levels in adult patients who are treated with highly active
      antiretroviral therapy. The findings are limited by the low prevalence of insulin
      resistance in the study sample and the small sample size.

PMID- 15561495
TI  - Relationship between stimulus complexity and neuronal activity in the
      inferotemporal cortex of the macaque monkey.
AB  - The single-unit activity of 217 cells was recorded from the inferotemporal cortex
      (IT) of two awake macaque monkeys while they performed a fixation task. The
      stimuli were coloured geometrical shapes or coloured representations of natural
      or artificial objects. To determine whether the stimuli could be separated into
      groups on the basis on neuronal population behaviour, the responses to the images
      were analysed by factor analysis and cluster analysis. It was a common result of
      each analysis that, on the basis of neuronal responses, the stimulus set could be
      separated into two groups, despite the lack of difference in mean response rate
      to them. Similar groups were formed when only the first half of the responses was
      analysed. The results suggest a differential coding of the images of simple
      geometrical shapes and of the images of complex, real (photographic) objects. We
      found significant differences between the two stimulus groups in physical
      features, other than size or luminance. Our results suggest that the same neurone
      population might respond differently to simple and complex images in the first
      150 ms of their responses. The differences might be attributed to "non-obvious"
      physical features of the stimuli, such as the amount of internal lines in the
      images, colourfulness and the length of perimeter of the stimuli.

PMID- 15561496
TI  - Flexibility in spatial and non-spatial feature grouping: an event-related
      potentials study.
AB  - Early perceptual grouping was studied using 256-channels event-related potentials
      in a choice response task. The task involved the detection of a triangle
      configuration of Gabor patches among patches of different spatial frequencies.
      The influence of two task-irrelevant factors was compared. One was the spatial
      proximity relation between the target patches and the other their relative
      orientation, a non-spatial relationship. Non-spatial effects were predominant in
      early peaks N64 and P100 in the occipital areas, and were reduced in size for
      later peaks. Spatial effects started from N180 in the occipital areas and
      continued in P250 and P430 in the central areas, increasing in size with time.
      These findings constitute a case of reversal of the usual order of spatial and
      non-spatial feature processing, illustrating that the flexibility in the early
      visual system may be greater than previously assumed.

PMID- 15561497
TI  - Retinotopic organization of visual mental images as revealed by functional
      magnetic resonance imaging.
AB  - In this study, we used event-related functional magnetic resonance imaging to
      investigate whether visual mental images retinotopically activate early visual
      cortex. Six participants were instructed to visualize or view horizontally or
      vertically oriented flashing bow-tie shaped stimuli. When compared to baseline,
      imagery globally activated Area V1. When the activation evoked by the stimuli at
      the different orientations was directly compared, distinct spatial activation
      patterns were obtained for each orientation in most participants. Not only was
      the topography of the activation patterns from imagery similar to the topography
      obtained with a corresponding visual perception task, but it closely matched the
      individual cortical representation of either the horizontal or the vertical
      visual field meridians. These findings strongly support that visual imagery and
      perception share low-level anatomical substrate and functional processes. Binding
      of spatial features is suggested as one possible mechanism.

PMID- 15561498
TI  - Recalibration of temporal order perception by exposure to audio-visual
      asynchrony.
AB  - The perception of simultaneity between auditory and visual information is of
      crucial importance for maintaining a coordinated representation of a multisensory
      event. Here we show that the perceptual system is able to adaptively recalibrate
      itself to audio-visual temporal asynchronies. Participants were exposed to a
      train of sounds and light flashes with a constant time lag ranging from -200
      (sound first) to +200 ms (light first). Following this exposure, a temporal order
      judgement (TOJ) task was performed in which a sound and light were presented with
      a stimulus onset asynchrony (SOA) chosen from 11 values between -240 and +240 ms.
      Participants either judged whether the sound or the light was presented first, or
      whether the sound and light were presented simultaneously or successively. The
      point of subjective simultaneity (PSS) was, in both cases, shifted in the
      direction of the exposure lag, indicative of recalibration.

PMID- 15561499
TI  - Memory structures for encoding and retrieving a piece of music: an ERP
      investigation.
AB  - This study examined behavioral and neural correlates of expert musical memory,
      specifically the hypothesis that particular bars within a complex piece of music
      would serve as structural markers for encoding to and retrieval from memory. Six
      pianists were asked to learn and memorize a set prelude by J.S. Bach for
      performance, and to identify bars that they employed for structuring the prelude
      into component sections. Following performance from memory, the participants took
      part in a visual recognition memory task, in which single bars from the prelude
      had to be distinguished from matched new bars. During the recognition task, the
      electroencephalogram (EEG) was recorded, and event-related potentials (ERPs) from
      correctly identified prelude stimulus trials were averaged according to their
      hypothesized status into "structural" and "nonstructural" bars. The results
      showed that correct identification of structural bars was significantly faster
      (and tended to display higher accuracy) than recognition of non-structural ones.
      In addition, recognition of structural bars was associated with a significantly
      greater negative ERP peak of 300-400 ms latency and a right centro-parietal scalp
      distribution. This mid-latency negativity appears to index processing of stimuli
      that served as cues for encoding and retrieval of a complex semantic structure,
      and is qualitatively and conceptually different from other previously identified
      recognition memory ERPs (such as the "old/new" effect), as well as from the
      classic N400 ERP. The data support existing theories of expert memory and music
      cognition.

PMID- 15561500
TI  - Reinforcement learning and decision making in monkeys during a competitive game.
AB  - Animals living in a dynamic environment must adjust their decision-making
      strategies through experience. To gain insights into the neural basis of such
      adaptive decision-making processes, we trained monkeys to play a competitive game
      against a computer in an oculomotor free-choice task. The animal selected one of
      two visual targets in each trial and was rewarded only when it selected the same
      target as the computer opponent. To determine how the animal's decision-making
      strategy can be affected by the opponent's strategy, the computer opponent was
      programmed with three different algorithms that exploited different aspects of
      the animal's choice and reward history. When the computer selected its targets
      randomly with equal probabilities, animals selected one of the targets more
      often, violating the prediction of probability matching, and their choices were
      systematically influenced by the choice history of the two players. When the
      computer exploited only the animal's choice history but not its reward history,
      animal's choice became more independent of its own choice history but was still
      related to the choice history of the opponent. This bias was substantially
      reduced, but not completely eliminated, when the computer used the choice history
      of both players in making its predictions. These biases were consistent with the
      predictions of reinforcement learning, suggesting that the animals sought optimal
      decision-making strategies using reinforcement learning algorithms.

PMID- 15561501
TI  - Quantitative EEG analysis for assessment to 'plan' a task in amyotrophic lateral
      sclerosis patients: a study of executive functions (planning) in ALS patients.
AB  - An attempt has been made to study the ability of patients with amyotrophic
      lateral sclerosis (ALS) to 'plan' a task. Electroencephalogram (EEG) data
      corresponding to 'planning of a movement task' is analyzed in comparison with a
      normal relaxed state. The study was conducted on 12 patients with ALS (6 males, 3
      females, mean age 46.75 years) and on same number of controls (10 males, 2
      females, mean age 48.75 years) to evaluate a difference in the ability to 'plan'
      a movement task between them. Patients with ALS were divided in two groups
      defined by unclear/clear speech. It has been observed that patients with ALS
      having unclear speech (Group I) showed considerable reduction (p<0.0001) in
      'planning' a movement task, whereas patients with ALS having clear speech (Group
      II) showed no deficit in 'planning' a movement task (p=0.0577), both in
      comparison with age-matched controls. Apart from supporting the earlier reports
      of a possible extended neuronal degeneration across wide area of the frontal
      lobes, the findings reveal a possible reduction in planning, an executive
      function of the prefrontal cortex of brain, and also reveal that speech
      impairment may be associated with cognitive deficits in patients with ALS.

PMID- 15561502
TI  - Gait-dependent motor memory facilitation in covert movement execution.
AB  - In the current study, we examined whether sensorimotor information stored in
      short-term memory may influence the temporal features between overt and covert
      execution of human locomotor movements and, furthermore, to examine to what
      extent such influence may depend on the ongoing gait activity. The subjects
      (n=20) who participated in the experiment were separated in two groups and
      instructed to walk (overt execution) or imagine walking (covert execution) along
      three locomotor paths: horizontal, uphill and downhill. The subjects of the first
      group, labeled in block, performed all the covert trials before executing the
      corresponding overt trials, while the subjects of the second group, labeled in
      serial, alternated between overt and covert movements. The overt and covert
      durations were recorded by means of an electronic stopwatch. We found high
      temporal similarities between overt and covert execution for both groups and for
      all the locomotor paths. Nevertheless, the execution of imagined movements was
      more variable compared to their actual counterparts. In addition, timing
      variability of covert movements was smaller for the group in serial compared to
      the group in block. This decrease in timing variability was larger for the
      horizontal walking compared to uphill or downhill locomotion. Furthermore, linear
      regression analysis performed on the data of the group in serial showed close
      temporal relationships between each successive overt and covert execution. These
      relationships were stronger when walking along the horizontal vs. sloped paths.
      Therefore, our results on timing variability provide evidence for gait-dependent
      motor memory facilitation in covert movement execution. We propose that gait
      dependent contribution of sensory feedback information to movement regulation may
      account for these findings.

PMID- 15561503
TI  - Excitotoxic lesions of the medial striatum delay extinction of a reinforcement
      color discrimination operant task in domestic chicks; a functional role of reward
      anticipation.
AB  - To reveal the functional roles of the striatum, we examined the effects of
      excitotoxic lesions to the bilateral medial striatum (mSt) and nucleus accumbens
      (Ac) in a food reinforcement color discrimination operant task. With a food
      reward as reinforcement, 1-week-old domestic chicks were trained to peck
      selectively at red and yellow beads (S+) and not to peck at a blue bead (S-).
      Those chicks then received either lesions or sham operations and were tested in
      extinction training sessions, during which yellow turned out to be nonrewarding
      (S-), whereas red and blue remained unchanged. To further examine the effects on
      postoperant noninstrumental aspects of behavior, we also measured the "waiting
      time", during which chicks stayed at the empty feeder after pecking at yellow.
      Although the lesioned chicks showed significantly higher error rates in the
      nonrewarding yellow trials, their postoperant waiting time gradually decreased
      similarly to the sham controls. Furthermore, the lesioned chicks waited
      significantly longer than the controls, even from the first extinction block. In
      the blue trials, both lesioned and sham chicks consistently refrained from
      pecking, indicating that the delayed extinction was not due to a general
      disinhibition of pecking. Similarly, no effects were found in the novel training
      sessions, suggesting that the lesions had selective effects on the extinction of
      a learned operant. These results suggest that a neural representation of memory
      based reward anticipation in the mSt/Ac could contribute to the anticipation
      error required for extinction.

PMID- 15561504
TI  - Changing patterns of brain activation during category learning revealed by
      functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) was used to investigate neural
      changes as a function of category learning in normals (n=8). Subjects were
      trained to classify patterns of dots into four categories over 4 consecutive
      days. fMRI monitored the changes that occurred during learning prior to training
      and then following each training session. During fMRI, subjects determined
      whether two patterns of dots were members of the same category. The behavioral
      changes that occurred as a result of the training were observed as increases in
      response accuracy within shortened response times. fMRI illustrated initial
      increases in volumes of activation distributed across the known visuospatial
      processing networks. The regions affected by learning were identified as those
      involved in the planning and execution of eye movements (frontal and
      supplementary eye fields, FEF and SEF), spatial attention (superior and inferior
      parietal lobules, SPL and IPL) and visual processing (primary, secondary, and
      tertiary visual cortices). The volumes of activation then decreased as training
      progressed further. Of the two proposed mechanisms for learning, that of
      strengthened connectivity on a given network and that of selection of different
      networks, our data supports the former.

PMID- 15561505
TI  - Impaired spatial learning after hypergravity exposure in rats.
AB  - Most astronauts experience spatial disorientation after exposure to
      weightlessness, indicating that constant gravity is utilized as a stable external
      reference during spatial cognition. We attempted to elucidate the role of
      constant gravity in spatial learning using a radial arm maze test on rats housed
      in a hypergravity environment (HG) produced by a centrifuge device. Male Wistar
      rats were kept in 2G linear acceleration for 2 weeks before the spatial learning
      task, which lasted for 10 days. The control rats were placed close to the
      centrifuge device but not exposed to hypergravity. Spatial learning was evaluated
      by the accuracy and the re-entry rate, which were the rate of correct arm entries
      and the rate of entries into the arms that they had already visited,
      respectively. Locomotor activity was measured by number of entries per minute.
      The number of baits the animal took per minute was also measured. The results
      showed that accuracy was significantly inferior and the re-entry rate was
      significantly higher in the HG rats than in the controls, suggesting that animals
      use a constant gravity as a stable external reference in spatial learning.
      However, these differences disappeared at 5 days later, indicating that the HG
      rats learned the spatial task more rapidly than the controls. Locomotor activity
      was higher in the HG rats and there was no difference in number of baits per
      minute between the HG and control animals. In conclusion, if one sensory cue
      necessary for spatial cognition is disturbed by gravity change, animals can
      subsidize with other sensory cues such as proprioceptive and motor efference copy
      signals through increased locomotor activities.

PMID- 15561506
TI  - Poor insight in traumatic brain injury mediated by impaired error processing?
      Evidence from electrodermal activity.
AB  - Impaired deficit awareness is common following traumatic brain injury (TBI) and
      is a major obstacle to rehabilitation. We have previously confirmed the presence
      of impaired error awareness in TBI using a highly discriminating go/no-go
      procedure. In the present study, we extend this work to try to identify more
      closely the nature of the error awareness deficit using measures of electrodermal
      activity (EDA). Sixteen participants with TBI and sixteen age-, sex-, and
      education-matched controls performed the Sustained Attention to Response Task
      (SART), while EDA was recorded. TBI detected significantly fewer errors compared
      to controls. EDA was significantly attenuated for TBI participants even to errors
      of which they were aware; error detection rates and EDA amplitude were also
      correlated. These findings suggest that poor insight following TBI may result, in
      part, from impaired error processing abilities.

PMID- 15561507
TI  - An event-related potential study of two kinds of source judgment errors.
AB  - The neural correlates of source judgment errors for confusable and nonconfusable
      source-item pairings were investigated. At study, subjects were presented with a
      series of lists of word pairs. Word pairs belonging to the same list were formed
      by pairing one of two associated words with different associates of an unstudied
      theme word (e.g., ship-frost, captain-chilly, ship-freeze, captain-frigid, etc.,
      in one list; wife-pane, husband-glass, wife-curtain, husband-sill, etc., in
      another list). At test, subjects discriminated 'Old pairs' (e.g., ship-frost)
      from 'Intra' rearranged pairs (e.g., ship-chilly), 'Inter' rearranged pairs
      (e.g., ship-pane), and 'Old-New' pairs (e.g., ship-bulb). Event-related
      potentials (ERPs) were recorded for each class of test item. Similar proportions
      of 'yes' responses to Old and Intra rearranged pairs were observed, but the false
      alarm rate for Inter rearranged pairs was markedly lower. ERPs elicited by
      correctly classified Old pairs and false alarms to Intra rearranged pairs were
      indistinguishable and exhibited 'left parietal' and 'right frontal' effects,
      characteristic of recollection-based recognition. ERPs for false alarms to Inter
      rearranged pairs did not show these effects. It is concluded that source judgment
      errors for confusable source-item pairings are mediated by the same processes
      that support correct source judgments. Such errors reflect recollection of gist
      information which is nondiagnostic with respect to source.

PMID- 15561508
TI  - Professor Ulrich Zwiener (1942-2004)-a tribute to ISP founding member.

PMID- 15561509
TI  - Some categories of general pathology and biology: health, disease, homeostasis,
      sanogenesis, adaptation, immunity New approaches and notions.

PMID- 15561510
TI  - Bile acids in physico-chemical host defence.
AB  - The discovery of the physico-chemical host defence is closely connected with the
      endotoxin research. It is well known that the toxic effects of endotoxins under
      experimental conditions can be induced only when they are administered
      parenterally. However, in naturally occurring entero-endotoxemic diseases (e.g.
      septic and various shocks, etc.), the endotoxin is absorbed from the intestinal
      tract. The cause and mode of translocation have been unknown. The generally used
      experimental shock models differ from natural diseases only in the mode by which
      endotoxin enters the blood circulation. If the common bile duct of rats was
      chronically canulated (bile-deprived animals) orally administered endotoxin was
      absorbed from the intestinal tract into blood circulation and provoked endotoxin
      shock. This translocation of endotoxins and the consequent shock can be prevented
      by sodium deoxycholate or natural biles. The bile acids split the endotoxin
      macromolecule into atoxic fragments. A similar detoxifying detergent action plays
      a significant role in host defence against infectious agents with outer
      lipoprotein structure (e.g. so-called 'big' viruses). This defence mechanism of
      macroorganisms based on the detergent activity of bile acids (end-products of the
      cholesterol metabolism) is called as physico-chemical defence system. Therefore,
      bile deficiency and the consequent endotoxemia are important components in the
      pathogenesis of certain diseases (e.g. sepsis, intestinal syndrome of radiation
      disease, hepato-renal syndrome, parvovirus infection, herpes, psoriasis,
      atherosclerosis, etc.). Bile acids may be used for the prevention and/or therapy
      of the above mentioned clinical conditions.

PMID- 15561511
TI  - CD26/DPPIV and response to hepatitis B vaccination.
AB  - The prevention of hepatitis B is important, since it is responsible for
      significant morbidity and mortality around the world. Unfortunately, hepatitis B
      vaccine does not always induce protective immunity. The lack of immune response
      to vaccine (non-responders) can depend on individual characteristics. The
      objective of this study was to correlate the CD26/DPPIV cellular expression and
      DPPIV serum activity with HBV vaccine response and its possible role as an
      indicator of immune competence acquisition. We also determined the cellular
      expression of CD3, CD19, CD56 and CD25 in peripheral blood T lymphocytes. Blood
      samples were obtained from 28 healthy human volunteers who were enrolled with a
      vaccination program. There were "responders" (RM = 13) and "non-responders" (NRM
      = 15), after vaccination. The lymphocyte populations were identified by flow
      cytometry. DPPIV serum activity was measured fluorimetrically. CD26 expression in
      responders (55.9 +/- 7.7%) versus in non-responders (51.9 +/- 7.0%) did not show
      a significant difference. The DPPIV serum activity in responders compared to in
      non-responder subgroup (59.9 +/- 8.4/50.3 +/- 10.6U/L) showed, however, a
      significant difference (P < 0.05). The expression of CD3, CD19 and CD56 on
      peripheral lymphocytes was similar between responders and non-responders. The
      expression of CD3CD26 (52.2 +/- 8.6%) and CD3CD25 (10.9 +/- 3.8%) in responders
      versus the expression of CD3CD26 (48.0 +/- 5.7%) and CD3CD25 (8 +/- 4.6%) in non
      responders did not show statistically significant difference. CD25 referred as a
      marker of T lymphocyte activation was increased in responders (15.8 +/- 4.5%)
      versus in non-responders (10.1 +/- 4.8%), showing a significant difference (P =
      0.003). It was, however, impossible to demonstrate an increase in CD3CD25 and
      CD3CD26 in the responder subgroup. This suggests that different lymphocyte
      subsets other than T cells are implicated in the response to hepatitis B
      vaccination.

PMID- 15561512
TI  - Mechanical stretch induces matrix metalloproteinase 1 production in human hepatic
      stellate cells.
AB  - In increasing portal blood flow, hepatic stellate cells (HSC) may be lengthened
      in response to mechanical stretch stimulation and their function may be changed.
      However, little is known about the influence of mechanical stretch on hepatic
      stellate cells. We examined production of matrix metalloproteinases (MMP), tissue
      inhibitors of metalloproteinases (TIMP), and extracellular matrix by hepatic
      stellate cells to investigate the relationship between mechanical stretch and
      hepatic fibrosis. LI90 cells, human hepatic stellate cells, were stretched
      cyclically using the Flexer cell strain unit. Concentrations of MMP1, MMP2,
      TIMP1, TIMP2, type I collagen C-telopeptide (1CTP), procollagen III propeptide
      (PIIIP), and hyaluronic acid in culture supernatants were determined. MMP1, MMP2,
      and TIMP1 mRNA expression was measured by reverse transcription-polymerase chain
      reaction (RT-PCR). In stretched LI90 cells, concentration of MMP1 showed an
      increase relative to unstretched cells, but concentrations of MMP2, TIMPl, and
      TIMP2 showed a decrease. MMP1/TIMP1 ratio and MMP1 mRNA expression showed an
      increase in stretched cells. Our finding suggested that in the early phase of
      portal hypertension, hepatic stellate cells increase production of MMPl and
      decrease production of TIMP1 and TIMP2, activated by mechanical stretch.

PMID- 15561513
TI  - Obstructive sleep apnea and ageing Myotonometry demonstrates changes in the soft
      palate and tongue while awake.
AB  - Upper airway dilator muscles are important in the pathogenesis of obstructive
      sleep apnea syndrome (OSAS). The present study compares changes of tissue
      properties between the soft palate and tongue in different age groups of apnea
      patients and healthy subjects. Materials and methods: OSAS patients diagnosed by
      polysomnography (15 patients - aged 30-70 years; 10 patients - aged 18-29 years)
      and healthy volunteers (10 subjects - aged 30-70 years; 10 patients - aged 18-29
      years) participated in the study. Computerized endopharyngeal myotonometry was
      used to measure the biomechanical properties - stiffness and elasticity of the
      soft palate [M. Veldi, V. Vasar, A. Vain, T. Hion, M. Kull, Computerized
      endopharyngeal myotonometry (CEM): a new method to evaluate the tissue tone of
      the soft palate in patients with obstructive sleep apnea syndrome, J. Sleep Res.
      9 (2000) 279-284; M. Veldi, V. Vasar, T. Hion, M. Kull, A. Vain, Ageing, soft
      palate tone and sleep-related breathing disorders, Clin. Physiol. 21 (2001) 358
      364] and lingual tissues [M. Veldi, V. Vasar, T. Hion, A. Vain, M. Kull,
      Myotonometry demonstrates changes of lingual musculature in obstructive sleep
      apnea, Eur. Arch. Otorhinolaryngol. 259 (2002) 108-112; M. Veldi, V. Vasar, T.
      Hion, A. Vain, M. Kull, Myotonometry demonstrates changes of soft palate and
      genioglossal muscle in obstructive sleep apnea, Sleep Med. 4 (Suppl. 1) (2003)
      S49] during wakefulness. Results: We did not find any statistical differences in
      tissue properties between the soft palate and the tongue tissues, either
      stiffness or elasticity, in young non-snorers and young patients of apnea (P >
      0.05). The stiffness of the soft palate of middle-aged apnea patients was
      increased compared with the tongue (P < 0.001). The elasticity of tongue of
      middle-aged patients of apnea was decreased compared with the soft palate (P <
      0.001). Conclusions: The biomechanical properties of the soft palate and the
      tongue undergo different changes in the case of snoring and upper airway
      obstruction and ageing.

PMID- 15561514
TI  - Antioxidant effects of alpha-, gamma- and succinate-tocopherols in guinea pig
      retina during ischemia-reperfusion injury.
AB  - The purpose of this study is to investigate the efficacy of alpha-tocopherol
      (AT), gamma-tocopherol (GT) and d-alpha-tocopherol polyethylene glycol 1000
      succinate (TPGS) in preventing the retinal injury followed by ischemia
      reperfusion (IR). The eyes of 40 adult male guinea pigs were used in the study.
      The guinea pigs were divided into five groups of eight rats each. First and
      second groups were used as control and IR groups, respectively. Third, fourth and
      fifth groups received subcutaneously AT, GT and TPGS, respectively. Treatment
      with each vitamin was performed before 5min of ischemia with reperfusion at 6h
      intervals for three times. Retinal ischemia was induced for 90min, then followed
      by reperfusion for 24h. The animals were killed at 24h of reperfusion. Lipid
      peroxidation (LP) and glutathione (GSH) levels were measured in right retinas by
      using a spectrofluorometer. Retinal GSH levels were found significantly lower (p
      < 0.002) in the IR group than in control group and there was a significant
      increase in the LP levels in IR group (p < 0.001). The decrease of GSH and
      increase of LP levels in the IR animals were significantly (p < 0.05 and 0.001)
      improved by the administration of the Vitamin E forms. When compared to GT group,
      there were no significant differences in LP levels in AT and TPGS groups.
      However, LP level in AT group was significantly (p < 0.01) lower than in the TPGS
      group. The GSH levels were higher (p < 0.001) in AT and TPGS groups than in IR
      group. Therefore, modulator effect of AT and GT were greater than that of TPGS.
      In conclusion, present data demonstrate that there is an increase in the LP in
      the retina of IR-induced animals and a decrease in the GSH levels. However,
      subcutaneous AT, GT and TPGS were effective in preventing retinal injury followed
      by ischemia-reperfusion. The subcutaneous AT may play a role in treating IR
      injury.

PMID- 15561515
TI  - Examining sites of interface between CAM and conventional health care: extending
      the sociological gaze.

PMID- 15561516
TI  - Treatment of patients with chronic headaches in a hospital for traditional
      Chinese medicine in Germany. A randomised, waiting list controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of a clinical treatment program with
      traditional Chinese medicine for migraine and tension-type headache. METHODS:
      Ninety-one patients with migraine, episodic or chronic tension-type headache
      according to the criteria of the International Headache Society were randomised
      into an experimental or a waiting list control group. Patients in the
      experimental group were treated 4 weeks in a hospital for traditional Chinese
      medicine after a baseline period of one month. Patients in the waiting list group
      continued their previous headache treatment. Main outcome measure was the
      difference in the number of days with headache of at least moderate intensity
      during baseline (month 1) and month 7. RESULTS: The difference in the number of
      days with headache of at least moderate intensity was 5.6 (S.D., 6.1) days in the
      experimental group and 1.2 (S.D., 4.5) days in the waiting list group (P <0.001).
      A reduction of more than 50% in headache days was observed in 52% of the patients
      in the experimental group and 16% in the waiting list group. Patients with
      migraine and a combination of migraine and episodic tension-type headaches
      improved more than patients with other headaches. CONCLUSION: The results of this
      study indicate that treatment in the hospital for traditional Chinese medicine in
      Kotzting is associated with lasting improvements in the majority of patients.

PMID- 15561517
TI  - The role of the state in the social inclusion of complementary and alternative
      medical occupations.
AB  - OBJECTIVE: To examine the views of government spokespersons regarding the efforts
      of five complementary and alternative medicine (CAM) groups (chiropractic,
      traditional Chinese medicine/acupuncture, naturopathy, homeopathy and Reiki) to
      take their place in the formal health care system. DESIGN: In this small scale,
      exploratory study, we conducted in-depth interviews with 10 key government
      officials at the federal (5), provincial (4) and municipal (1) levels. We used
      qualitative techniques such as constant comparison to describe and explain their
      responses to three main questions: (1) What should be the role of the state in
      the professionalization of CAM? (2) Is there a legitimate place for CAM groups in
      the formal health care system? and (3) Should CAM services be integrated with
      conventional medical care? SETTING: Ontario, Canada. RESULTS: The findings
      identify a fundamental tension between the various levels of government. Their
      mandate to protect the public comes into conflict with the obligation to respond
      to consumer pressure for CAM. Safety, efficacy and cost-containment were the
      chief explanations given for the government's slowness to catch up to consumers.
      They also mentioned fears of rising health care costs and the lack of cohesion
      among and between CAM groups as barriers to legitimacy and integration.
      CONCLUSION: Realizing the professional aspirations of CAM practitioners will
      depend on the outcome of a political contest between the public, the state and
      the established health care professions.

PMID- 15561518
TI  - Disclosure of CAM use to medical practitioners: a review of qualitative and
      quantitative studies.
AB  - BACKGROUND: Many people use complementary or alternative medicine (CAM). It is
      estimated that over 50% of patients that require health care use CAM either in
      conjunction with, or separate from, conventional health care. Despite the popular
      use of CAM, patients do not always inform their conventional medicine health
      carers of their CAM use. The medical practitioner is in most cases the first
      health care professional a person contacts concerning a health care matter, and
      needs to have a full history of a health problem to understand and provide
      optimum care. This literature review aims to provide an understanding of the
      degree to which patients disclose their use of CAM to their medical
      practitioners, and their reasons for not doing so. METHOD: A comprehensive
      literature search identified 12 studies published between 1993 and 2002 that
      examined what percentage of consumers did not disclose to their medical
      practitioners their use of CAM, and their reasons for not doing so. RESULTS: The
      rate of non-disclosure of those using CAM is as high as 77% in some studies. The
      main reasons patients provided for not disclosing their use of CAM to their
      medical practitioners were concerns about a negative response by the
      practitioners, the belief that the practitioner did not need to know about their
      CAM use, and the fact that the practitioner did not ask. DISCUSSION: The pre
      conceptions patients have that influence their non-disclosure may be based on
      three issues. First, beliefs and concerns that influence their decision-making,
      second personal experiences in their consultations with medical practitioners,
      and third, the desire for more control over their health care. Medical
      practitioners need to acknowledge the concerns and beliefs of patients in making
      their health care decisions, and work with patients so that the use of CAM is
      acknowledged and the patients' needs, beliefs and concerns respected.

PMID- 15561519
TI  - Determinants of complementary alternative medicine (CAM) use.
AB  - OBJECTIVE: The aim of this study was to describe the pattern of use of
      complementary alternative medicine (CAM) and identify the determinants of CAM use
      in a multi-ethnic Swedish primary health care practice population. METHODS: A
      questionnaire was handed out to 1433 patients aged 16 years and above who visited
      the Jordbro Health Centre (JHC) in Stockholm, Sweden, between 14 January and 30
      June 2002. The results were linked to computerised medical records. RESULTS:
      Seventeen percent of respondents had consulted a CAM provider during the
      preceding year and many patients had consulted several types of CAM providers.
      The most frequently CAM used was massage, followed by acupuncture, chiropractic
      and naprapathy. In the logistic regression, when adjusting for the influence of
      possible confounders, chronic disease and physical activity were the most
      important predictors of consultations with CAM providers. Users of CAM had had a
      higher number of consultations with medical professionals than had non-users of
      alternative medicine. CONCLUSIONS: In our study population CAM, defined here as
      "manual therapy", was used in addition to traditional therapies and was related
      to high use of health care services. Chronic disease and physical activity were
      significantly and independently related to use of CAM.

PMID- 15561520
TI  - The use of simplified constitutional indications for self-prescription of
      homeopathic medicine.
AB  - OBJECTIVES: To develop simplified constitutional indications for homeopathic
      medicines so that parents of children with recurrent upper respiratory tract
      infection (URTI) could choose homeopathic medicines for their children more
      "accurately", and to subsequently evaluate if these choices match the
      prescriptions of trained homeopaths. DESIGN AND SETTING: To initially select the
      most commonly used homeopathic medicines for URTI, data from a survey of 1097
      patients visiting 80 different Norwegian homeopaths were used. A simplified
      constitutional indication was then developed for the three homeopathic medicines
      most frequently prescribed for recurrent URTI and otitis media. The
      constitutional indications were developed by a group of five homeopaths and were
      then sent to 20 homeopaths for further evaluation. To evaluate the parents'
      choice of homeopathic medicines compared to the prescription by trained
      homeopaths, a group of 11 randomly selected homeopaths were asked to participate.
      They recruited parents of 70 child patients. RESULT: By using simplified
      constitutional indications for the three most commonly prescribed remedies,
      Calcarea carb, Pulsatilla and Sulphur, parents were able to choose the same
      homeopathic medicine as homeopaths' prescribed for 55% (95% CI 43-67) of children
      with URTI. There was excellent agreement between parents' choice and homeopaths'
      prescription for the three medicines (Kappa of 0.77, p<0.001). CONCLUSION:
      Simplified constitutional indications can be used to improve the quality of the
      choice of homeopathic medicines purchased over the counter (OTC) for self
      treatment.

PMID- 15561521
TI  - An approach to educating family practice residents and family physicians about
      complementary and alternative medicine.
AB  - Complementary and alternative medicine (CAM) in the context of medical education
      is a controversial topic among the medical community. With the increased
      popularity of complementary and alternative medicine, medical educators are faced
      with the need of educating physicians so they would become competent to
      communicate with patients about CAM. As academic medicine shows more interest in
      CAM, it is critical to develop initiatives to overcome physicians' attitudinal
      barriers toward CAM and develop an instruction strategy that can address these
      needs. An approach to educate family practice residents and family physicians
      about CAM is described in this article. This patient-centered teaching approach
      hinges on the belief that CAM and family medicine are closely related. It
      espouses utilizing critical thinking and basing decisions on evidence-based
      material. The course covered four main topics in CAM: herbal medicine,
      traditional Chinese medicine (TCM), homeopathy and complementary nutrition. The
      course had limited objectives of exposing physicians to the common methods in CAM
      and providing sufficient information, so physicians could provide their patients
      with an informed, safe and balanced advice. The instructions emphasized the
      importance of improving physician-patient relationship and enriching the
      participant both professionally and personally. Results of our study revealed
      that after the course physicians' referral to CAM became more selective, at the
      same time, their personal use of CAM also increased. This reflects the increased
      value of CAM in the physicians' own healthcare, as well as their improved
      knowledge of appropriate referral patterns. Most importantly, the course
      increased the physicians' awareness of the psychosocial aspect of clinical
      problems encountered in family practice and, through the close observation of CAM
      in practice, gave them an additional viewpoint to better understand the patient
      doctor relationship.

PMID- 15561522
TI  - Introduction to the research methods in CAM series.
AB  - There is increasing awareness of a need for rigorous research into complementary
      and alternative medicine, but as yet, limited guidance has been given to
      researchers, practitioners and students as to the range and scope of the various
      methodologies available and how existing methods can be modified for CAM
      research. This research methods series provides an outline of the main methods
      for researching CAM-related issues, including clinical trials, cross-sectional
      studies and qualitative methodologies. Drawing on the experiences of a range of
      experts in CAM research, each article in this series addresses the scope and
      strengths of a particular methodological approach. This series aims to convey the
      basis and objectives of particular methodologies within the context of CAM
      research, and thus, each paper will draw on actual examples of CAM research. It
      is intended to be of value both to inexperienced researchers and to those who are
      more experienced but are looking to broaden their range of knowledge. In this
      introduction, we outline some of the fundamental concepts for researching CAM,
      providing an overall sense of where each methodological approach outlined in this
      series fits in the 'order of things'. We outline different design strategies, the
      philosophical differences underpinning particular approaches to collecting data,
      and the issue of bias in research design and analysis.

PMID- 15561523
TI  - Conversation analysis.
AB  - Conversation analysis (CA) is well established as a means of exploring the
      interactional detail of conventional healthcare encounters. It is also becoming
      increasingly popular in action to CAM. This article outlines the main features of
      CA, how it can be used in a CAM context, and the type of information it can be
      expected to reveal. Examples of original CA data obtained from CAM consultations
      are presented to illustrate the CA method.

PMID- 15561524
TI  - Pragmatic clinical trials.
AB  - Both pragmatic and explanatory randomised controlled trials have a useful role to
      play in the evaluation of health care interventions. In this descriptive article,
      the key steps in conducting a pragmatic trial are described. The strengths and
      limitations of pragmatic trials are also discussed. The main strength of
      pragmatic trials is that they can evaluate a therapy as it is used in normal
      practice. Comparisons are made between pragmatic and explanatory trials, on the
      understanding that trials may have aspects to them that make the trial more of a
      hybrid. A case is made for the appropriate use and relevance of pragmatic trials
      in the evaluation of alternative and complementary medicine.

PMID- 15561525
TI  - Naturopathic and Western herbal medicine practice in Australia--a workforce
      survey.

PMID- 15561527
TI  - Intraoperative MRI developments.

PMID- 15561528
TI  - Basic principles of magnetic resonance imaging.
AB  - We have come full circle from spinning quarks to 3D medical images. The bulk of
      MRI is now performed using slice-selective gradients, during which RF energy is
      applied to excite the hydrogen nuclei. By stepping a phase-encoding gradient
      during each TR and using a frequency-encoding gradient as the data are sampled,
      the 3D human object can be reduced to many individual points or voxels. By
      acquiring multiple slices at once, the time efficiency of imaging can be vastly
      improved. Many newer strategies use variations of this technique to acquire
      multiple lines of data during a single echo, enshrining spin warp imaging as the
      most important method of signal acquisition for MRI.

PMID- 15561529
TI  - Quasi-real-time neurosurgery support by MRI processing via grid computing.
AB  - One problem of providing time-critical medical services over the grid is always
      its dependency on the Internet. It cannot be assumed that transfer ofa certain
      amount of data over the Internet is always achieved during a specified period.
      Such a requirement cannot be fulfilled by the infrastructure of the Web. There is
      always the risk of a network delay or even an overload. Because of this, another
      goal of this project is the evaluation of grid services versus the use of local
      services. A further point for future research related to the chain has to deal
      with the optimization approach for the linear registration step. Because the
      optimization uses the downhill simplex algorithm in a nine-dimensional search
      space, the number of iterations needed to find the optimum can vary dramatically.
      This makes linear registration the most unpredictable step of the chain in terms
      of execution time. It cannot be assured that the global optimum is found.
      Additional work has to be done in validating the registration accuracy, including
      the examination of the influence of intensity variations between intraoperative
      images as well as the influence of tumor resection and the presence of the opened
      skull versus the closed skull in the fluid-based registration.

PMID- 15561530
TI  - Functional MRI localizing in the cerebellum.
AB  - Mapping of cerebellar function by functional MRI now enables us not only to re
      establish older anatomic findings of somatotopic representations but to gain new
      insights in the function of the cerebellum and its intimate relations of cerebral
      regions to serving sensorimotor function, sensory discrimination, and cognitive
      processing. Consequently, it will change our understanding of neurologic and
      psychologic failures in patients with inborn errors or neurodegenerative diseases
      or after neurosurgical procedures.

PMID- 15561531
TI  - Proton magnetic resonance spectroscopic imaging in brain tumor diagnosis.
AB  - The current state of standard tumor diagnostics using contrast-enhanced MRI and
      biopsy is assessed in this review, and the progress of proton magnetic resonance
      spectroscopy (MRS) over the last 15 years is discussed. We summarize MRS basics
      and describe a typical magnetic resonance session for noninvasive routine tumor
      diagnostics at 1.5 T, including two-dimensional magnetic resonance spectroscopic
      imaging (MRSI). The results that can be obtained from such procedures are
      illustrated with clinical examples. Attention is turned to cutting-edge
      methodologic and clinical research at 3 T, with examples using high-resolution or
      very short echo-time three-dimensional MRSI. The current status and limitations
      in proton MRSI are discussed, and we look to the potential of faster data
      collection and even higher field strength.

PMID- 15561532
TI  - Diffusion tensor magnetic resonance imaging of brain tumors.
AB  - DTI seems to offer the possibility of adding important information to presurgical
      planning. Although experience is limited, DTI seems to provide useful local
      information about the structures near the tumor, and this seems to be useful in
      planning. In the future, DTI may provide an improved way to monitor
      intraoperative surgical procedures as well as their complications. Furthermore,
      evaluation of the response to treatment with chemotherapy and radiation therapy
      might also be possible. Although DTI has some limitations, its active
      investigation and further study are clearly warranted.

PMID- 15561533
TI  - A low-field intraoperative MRI system for glioma surgery: is it worthwhile?
AB  - As intraoperative MRI expands its presence, its use will undoubtedly increase in
      glioma surgery. The foregoing discussion makes it clear that its benefits are
      unsurpassed by any other existing system. Because of their radiographic
      characteristics and gross appearance, gliomas are particularly suited for
      intraoperative MRI-guided surgery. It enables us to localize gliomas and define
      tumor margins precisely when, during surgery, the difference between tumor and
      brain is not easy to discern. The images generated during surgery serve as a
      detailed and updated map within which navigation is performed with utmost
      precision. Its significance is further highlighted when dealing with tumors in
      eloquent areas of the brain, where uncertainties over the location of tumor in
      relation to important brain structures can hinder the removal of tumor. By
      providing accurate positional information and in conjunction with cortical
      mapping techniques, intraoperative MRI enhances the confidence of the surgeon to
      go forward with resection or to stop when reaching important cortex. It allows us
      to perform the resection to the desired limit without causing injury to nearby
      important structures, thereby preventing postoperative neurologic deficits. The
      tracking system guides us in targeting each minute part of the tumor with
      unprecedented accuracy, and the ability to update images makes possible the
      constant evaluation of the progress of surgery. This near-real-time imaging can
      eliminate the errors brought about by the brain shifting that occurs throughout
      surgery. It also serves the important purpose of verifying the presence and
      position of any remaining tumor in the operative field. By means of sequential
      imaging, additional resection can be performed on any remaining tumor until
      imaging shows completion. The unwanted occurrence of finding residual tumor on a
      postoperative scan is thus practically eliminated. As a result, the surgical goal
      of complete or optimal resection can be achieved without any guesswork.
      Ultimately, what this means for the glioma patient is increased likelihood of
      longer survival brought about by a more thorough tumor resection. Intraoperative
      MRI addresses many of the surgical challenges posed by gliomas. As it becomes
      more available, there will come a point when the prevailing persuasion will be
      that some poorly defined tumors near eloquent cortex should not be operated on
      without intraoperative MRI. In the final analysis, not only is intraoperative MRI
      worthwhile but it will, in all likelihood, become a standard of care for many
      glioma cases.

PMID- 15561534
TI  - Intraoperative magnetic resonance imaging at 0.12 T: is it enough?
AB  - Low magnetic field strength MRI provides the anatomic information needed for
      intracranial procedures in which intraoperative imaging is needed. Stereotactic
      accuracy is proven. The distinct advantage of this technologic approach is that
      it allows the neurosurgical team to operate an iMRI system with minimal
      disruption to the OR routine. Technical improvements are likely to increase the
      power and versatility of low field strength iMRI. Logic dictates that ergonomics
      and economics will make this the iMRI technique desired by most neurosurgeons.

PMID- 15561535
TI  - Adaptation of a standard low-field (0.3-T) system to the operating room: focus on
      pituitary adenomas.
AB  - iMRI is a reliable and safe tool to monitor the extent of resection and to avoid
      complications in the transsphenoidal surgical approach for pituitary tumors. The
      best indication for its application in transsphenoidal surgery is for patients
      with pituitary macroadenomas with suprasellar extension. The low-field 0.3-T
      magnet has a diagnostic imaging quality that provides surgeons with good
      intraoperative detail of the anatomic relations in the sellar region. In our
      experience, iMRI provided a distinct benefit in planned STR for invasive
      macroadenomas that compress the optic chiasm and in planned GTR for noninvasive
      tumors. The iMRI design adopted at our center includes important features, such
      as the use of ferromagnetic surgical instruments, elimination of patient
      transportation, and capability as a shared resource, that allow multipurpose
      diagnostic use and increased cost-effectiveness.

PMID- 15561536
TI  - 1.5 T: spectroscopy-supported brain biopsy.
AB  - The technique for performing brain biopsy has evolved significantly over the last
      three decades. Intraoperative MRI guidance has enhanced the diagnostic rate for
      brain biopsy by now allowing neurosurgeons to compensate for brain shift while
      performing the procedure in near-real time. The development of a trajectory guide
      enables the neurosurgeon to determine a safe and accurate path for intraoperative
      MRI-guided brain biopsy and to secure the position of the needle within the
      target tissue. Magnetic resonance spectroscopy (MRS) has been used to help
      distinguish recurrent brain tumor from the effect of previous treatments by
      measuring specific metabolites within the area of concern. Combining the use of a
      trajectory guide with MRS should enhance the diagnostic yield for MRI-guided
      brain biopsy.

PMID- 15561537
TI  - Epilepsy surgery with intraoperative MRI at 1.5 T.
AB  - Despite the infancy of iMRI in epilepsy surgery and the paucity of literature on
      this topic, some conclusions may be reached. Although iMRI is a useful adjunct
      during epilepsy procedures, a randomized control trial is necessary to determine
      its true impact.

PMID- 15561538
TI  - 1.5 T: intraoperative imaging beyond standard anatomic imaging.
AB  - Intraoperative high-field MRI with integrated microscope-based neuronavigation is
      a safe and reliable technique providing immediate intraoperative quality control.
      Major indications are pituitary tumor, glioma, and epilepsy surgery.
      Intraoperative high-field MRI provides intraoperative anatomic images at high
      quality that are up to the standard of pre- and postoperative neuroradiologic
      imaging. Compared with previous low-field MRI systems used for intraoperative
      imaging, not only is the image quality is clearly superior but the imaging
      spectrum is much wider and the intraoperative work flow is improved. Furthermore,
      high-field MRI offers various modalities beyond standard anatomic imaging, such
      as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI.

PMID- 15561539
TI  - Future perspectives for intraoperative MRI.
AB  - MRI-guided neurosurgery not only represents a technical challenge but a
      transformation from conventional hand-eye coordination to interactive
      navigational operations. In the future, multimodality-based images will be merged
      into a single model, in which anatomy and pathologic changes are at once
      distinguished and integrated into the same intuitive framework. The long-term
      goals of improving surgical procedures and attendant outcomes, reducing costs,
      and achieving broad use can be achieved with a three-pronged approach: 1.
      Improving the presentation of preoperative and real-time intraoperative image
      information 2. Integrating imaging and treatment-related technology into therapy
      delivery systems 3. Testing the clinical utility of image guidance in surgery The
      recent focus in technology development is on improving our ability to understand
      and apply medical images and imaging systems. Areas of active research include
      image processing, model-based image analysis, model deformation, real-time
      registration, real-time 3D (so-called "four-dimensional") imaging, and the
      integration and presentation of image and sensing information in the operating
      room. Key elements of the technical matrix also include visualization and display
      platforms and related software for information and display, model-based image
      understanding, the use of computing clusters to speed computation (ie, algorithms
      with partitioned computation to optimize performance), and advanced devices and
      systems for 3D device tracking (navigation). Current clinical applications are
      successfully incorporating real-time and/or continuously up-dated image-based
      information for direct intra-operative visualization. In addition to using
      traditional imaging systems during surgery, we foresee optimized use of molecular
      marker technology, direct measures of tissue characterization (ie, optical
      measurements and/or imaging), and integration of the next generation of surgical
      and therapy devices (including image-guided robotic systems). Although we expect
      the primary clinical thrusts of MRI-guided therapy to remain in neurosurgery,
      with the possible addition of other areas like orthopedic, head, neck, and spine
      surgery, we also anticipate increased use of image-guided focal thermal ablative
      methods (eg, laser, RF, cryoablation, high-intensity focused ultrasound). By
      validating the effectiveness of MRI-guided therapy in specific clinical
      procedures while refining the technology that serves as its underpinning at the
      same time, we expect many neurosurgeons will eventually embrace MRI as their
      intraoperative imaging choice. Clearly, intraoperative MRI offers several
      palpable advantages. Most important among these are improved medical outcomes,
      shorter hospitalization, and better and faster procedures with fewer
      complications. Certain economic and practical barriers also impede the large
      scale use of intraoperative MRI. Although there has been a concerted technical
      effort to increase the benefit/cost ratio by gathering more accurate information,
      designing more localized and less invasive treatment devices, and developing
      better methods to orient and position therapy end-effectors, further research is
      needed. Indeed, the drive to improve and upgrade technology is ongoing.
      Specifically, in the context of the real-time representation of the patient's
      anatomy, we have improved the quality and utility of the information presented to
      the surgeon, which, in turn, contributes to more successful surgical outcomes. We
      can also expect improvements in intraoperative imaging systems as well as
      increased use of nonimaging sensors and robotics to facilitate more widespread
      use of intraoperative MRI.

PMID- 15561542
TI  - What the rehabilitation professional and the consumer need to know.
AB  - Many people with disabilities from early in life (eg, cerebral palsy,spinal cord
      injury, and polio) are beginning to live into middle and late life. Recent
      evidence indicates that these individuals often do not age in a typical manner. A
      large proportion of these people develop new medical, functional, and support
      problems by the time they reach their late 40s and early 50s. This article
      reviews many of those changes and points to some ways to help intervene. Changes
      in rehabilitation education and programs need to begin to incorporate these
      recent findings.

PMID- 15561543
TI  - Age-related changes in muscles and joints.
AB  - Aging muscle and joint changes can have a tremendous impact on the functionality
      of elderly people with and without disabilities. Studies in animal models have
      shown some potentially beneficial interventions (eg, gene therapy). Further
      research is needed to ascertain their benefits in humans. A better understanding
      of mechanisms by which skeletal muscle and joint changes take place in a
      geriatric population will be helpful to find reasonable ways to prevent age
      related change and improve disability. Although some agents have been reported to
      have significant positive effects, further studies are needed to determine long
      term side effects. More information is needed with respect to the changes in
      muscles and joints in various disabilities.

PMID- 15561544
TI  - Exercise and physical activity in persons aging with a physical disability.
AB  - The relationship between physical functioning and physical activity isa
      reciprocal one; physical functioning provides the individual with the capability
      to engage in physical activities, and physical activity helps to maintain and in
      some cases improve physical functioning. This reciprocal relationship, coupled
      with the high prevalence of physical inactivity among persons aging with a
      disability, has profound implications for rehabilitation practice, especially in
      evaluating intermediate and long-term outcomes of clinical practice. For
      rehabilitation to play a role in the long-term maintenance and enhancement of
      physical functioning among persons with disabilities, increasing participation in
      various types of physical activity in the community must be part of the recovery
      and maintenance continuum. There is also a critical need to identify specific
      doses of physical activity for specific disabilities and secondary conditions.
      HMOs and other health insurers will require evidence-based outcomes before
      establishing reimbursement procedures for physical activity programs for persons
      aging with a physical disability.

PMID- 15561545
TI  - Practical considerations in the assessment and treatment of pain in adults with
      physical disabilities.
AB  - Adults aging with physical disabilities experience a variety of pain disorders
      that affect their functionality and QOL. It is important that clinicians caring
      for this population be knowledgeable about this common symptom and be able to
      perform a thorough history and physical examination. In addition, it is
      imperative to have a good working knowledge of the strengths and limitations of
      the treatments available.

PMID- 15561546
TI  - Fatigue in the elderly population.
AB  - Fatigue in the elderly population is a complex phenomenon. Although a number of
      factors contributing to the fatigue have been identified, its basic mechanism
      remains elusive. Additional research on prevalence, identification, diagnosis,
      severity of fatigue, and associated factors and the role of exercise as an
      effective treatment modality could lead to a better understanding of the causal
      factors.

PMID- 15561547
TI  - Falls in the elderly population.
AB  - Falls among elderly persons remain a difficult problem with few easy solutions.
      Falls are symptomatic of underlying clinical deficits, and a multidisciplinary
      approach is essential in identifying the risk factors and appropriate treatments
      for these patients. Patients with chronic medical conditions, such as spinal cord
      injury, traumatic brain injury, and amputations, possess additional unique risk
      factors that must be addressed. Interventions include treatment of potentially
      reversible medical conditions such as B12 and vitamin D deficiencies and home
      modifications,balance and exercise training programs, medication modification,
      hip protectors, and monitoring devices. Physicians, patients, family members, and
      caretakers should be reminded that minimizing falls risk requires persistence,
      patience, and dedication. Progress may not be noted overnight, but adherence to
      recommendations correcting intrinsic and extrinsic factors can help to minimize
      falls and their potentially devastating complications.

PMID- 15561548
TI  - Aging with spinal cord injury.
AB  - The years after SCI may be associated with acceleration of the aging process
      because of diminished physiologic reserves and increased demands on functioning
      body systems. Clinicians with expertise in the treatment and prevention of SCI
      specific secondary complications need to collaborate with gerontologists and
      primary care specialists and need to invest in the training of future physicians
      to ensure a continuum of accessible, cost-effective, and high-quality care that
      meets the changing needs of the SCI population. Managed care payers often do not
      adequately cover long-term disability needs to prevent secondary SCI-specific
      complications. In this era of increasing accountability, evidence-based clinical
      practice guidelines are needed to document scientific evidence and professional
      consensus to effectively diagnose, treat, and manage clinical conditions; to
      reduce unnecessary testing and procedures; and to improve patient outcomes.
      Longitudinal research is needed to minimize cohort effects that contribute to
      misinterpretation of cross-sectional findings as representative of long-term
      changes in health and functioning. However, longitudinal studies confound
      chronologic age, time since injury, and environmental change. Thus, time
      sequential research, which controls for such confounding effects, is essential,
      as is research on the effects of gender,culture, and ethnicity. If we consider
      how much progress has been made over the past 50 years with respect to SCI
      mortality related to infectious disease, we can expect to achieve even greater
      progress against the effects of aging in the next 50 years. Recent developments
      in molecular biology regarding growth and neuro-trophic factors are bringing us
      closer to the goal of repairing the damaged spinal cord. The challenge remains
      for rehabilitation professionals to provide the most comprehensive and holistic
      approach to long-term follow-up, with an emphasis on health promotion and disease
      prevention, to postpone functional decline and enhance QOL.

PMID- 15561549
TI  - The impact of age on traumatic brain injury.
AB  - Older individuals with TBI differ from younger adults with TBI in several ways,
      including their incidence rates, etiology of injury, nature of complications,
      lengths of hospitalization, functional outcomes, and mortality. Despite the
      greater likelihood of poorer functional outcomes, older adults with TBI often
      achieve good functional outcomes and can live in community settings after
      receiving appropriate rehabilitation services, although at higher costs and
      longer hospitalizations than younger individuals. The future of rehabilitation
      care for elderly patients after TBI is uncertain due to financial limitations
      associated with the implementation of the PPS payment system by CMS. Little is
      known regarding the long-term impact of TBI on individuals as they age, but this
      is an important issue as the population ages.

PMID- 15561550
TI  - The geriatric amputee.
AB  - There are special aspects of aging with an amputation and with being elderly at
      the time of an amputation. Older adults who have undergone amputation have many
      issues to contend with, including comorbidities that affect postoperative care
      and rehabilitation, general deconditioning and loss of mobility (especially if
      the onset of rehabilitation is delayed), and lack of social support upon
      returning to the community. These problems are compounded by a lack of knowledge
      about caring for the residual limb and prosthesis, maintenance of general health,
      and management of comorbid conditions. People who have sustained an amputation at
      an early age and who are ambulatory may find increasing difficulties as they age.
      Acquired chronic disease occurs more frequently as people age. These conditions
      can adversely affect function after amputation. Prosthetic designs may need
      modification because certain components may become more difficult to use. The
      prevention of a (second) amputation results in saving a limb and preserving self
      image and independent function. Considering the emotional and economic cost of
      amputation and lifelong management of a prosthesis, it is worth the time and
      effort to practice preventive measures. Should amputation become necessary,
      careful patient assessment, compassionate management, and communication among the
      team members results in a more favorable outcome. Including the physiatrist early
      in the clinical course makes this process easier.

PMID- 15561551
TI  - Aging in polio.
AB  - For a disease that was "conquered" some 40 years ago with the onset of effective
      vaccination, the issues of long-term survivors of paralytic polio as they age
      continue to present challenges to rehabilitation specialists. Aging with polio is
      a definition of PPS. There are over a million patients with PPS in the United
      States. Management has to include the appropriate use of exercises, appropriate
      bracing and support, and, in the case of bulbar and respiratory symptoms, the
      appropriate use of speech therapy services and ventilatory support. There are no
      prospective randomized trials studying the treatment of weakness and fatigue in
      PPS. Pharmacologic interventions are limited at this time but include
      anticholinergics for muscle weakness and dopaminergic agents or amantadine to
      control central fatigue. The pathophysiology of aging with polio is consistent
      with neuronal loss and denervation lying at the heart of the developing disorder,
      whereas the central nervous system components of the fatigue syndrome may be
      related to central changes with neuronal loss in the basal ganglia and reticular
      activating system. Many of the survivors of the polio epidemics are in their
      later retirement years, and their needs will increase as they have other
      disabilities due to natural aging. Sensitivity to some of the special issues in
      PPS may help to avoid complications. Polio is an active infection in the third
      world. Although great strides have been made, the disease is endemic in eight
      nations and is threatening to spread. The lessons learned in treating PPS now
      will be useful in years to come as these individuals age and manifest PPS in the
      future.

PMID- 15561552
TI  - Aging with multiple sclerosis.
AB  - The chronic and progressive nature of MS may be overwhelming to the patient and
      the family. It is vital for the clinician to develop a system of periodic
      evaluations and interventions that monitor the disease and address the effects on
      the patient's physical, psychologic, social, and vocational functioning. MS
      patients are susceptible to other diseases of aging, such as stroke, cancer,
      heart disease, and diabetes, and need to be evaluated and treated for these
      conditions. Obtaining appropriate routine medical care may become difficult in
      less mobile patients because many clinicians' offices are unable to accommodate
      handicapped patients. Careful coordination and referral to handicap-accessible
      centers may be required to ensure adequate treatment. Nearly half of MS patients
      die from complications of their disease. Other major causes of mortality are
      malignancy (16%), suicide (15%), and myocardial infarction (11%). Age-appropriate
      cancer screenings and cardiac evaluation are necessary. Depression is an
      important factor in geriatric MS patients despite the fact that most MS patients
      have an easier time adjusting to the aging process than the general population.
      There are many unanswered questions for the older MS population due to the
      paucity of research, but future studies may rectify this situation. Although
      there is no cure for MS, the clinician can play a key role in helping the patient
      and family adapt to the illness and improve their quality of life. Resources are
      available for the clinician, the patient, and family members.

PMID- 15561553
TI  - Aging with cerebral palsy.
AB  - Before the mid-twentieth century, few people with CP survived to adulthood. Now,
      65% to 90% of children with CP survive. Because of improvements in intensive care
      techniques leading to the increased survival of very low-birth-weight infants and
      the increased longevity of the general population, there are a large number of
      disabled adults requiring medical care. Adults with CP have medical and social
      issues that are unique to them. Although there is an increasing awareness of the
      rights of people with disabilities, there is more work to be done particularly as
      relates to the cost and availability of adaptive equipment and exercise. In
      recent years, more attention has been given to studying the needs of this growing
      part of the population. However, much remains to be investigated to improve the
      quality of life for these patients.

PMID- 15561554
TI  - Aging with cardiopulmonary disease: the rehab perspective.
AB  - Cardiac disease is a leading cause of disability. This article reviews the
      epidemiology, pathophysiology, and risk factors for coronary heart disease. We
      explore the latest research in risk stratification, exercise training, and
      screening for cardiac rehabilitation in the elderly patient. The rehabilitation
      specialist will see how this select population differs in their medical and
      rehabilitative needs.

PMID- 15561555
TI  - Delivery of rehabilitation services to people aging with a disability.
AB  - The disabled elderly population continues to grow. Systems of care for the
      disabled elderly are vast, ranging from inpatient facilities to outpatient
      programs and home programs. Recent advances in technology allow us to reach
      patients in their homes through telemedicine. Support services within the
      community are growing, and case managers are becoming more necessary as it
      becomes more difficult to navigate the health care system. As providers of
      rehabilitative services, we must help our patients find the most appropriate
      setting to receive care. As the focus continues to shift from inpatient to
      outpatient care and to home services, we must approach health care in a dynamic
      fashion and with flexibility. We must be advocates for our patients and their
      caretakers. Significant research questions remain, and health care policy
      requires development. As the population ages and the disabled elderly population
      become a focus of fiscal experts, we must look to provide the most cost-effective
      yet functionally productive health care. We may shift from focusing on functional
      performance in a therapy gym or inpatient rehabilitation unit to functional
      performance at home. We must focus on IADL and QOL indicators and must strive to
      find ways to provide efficient, cost-effective care. Medicaid, Medicare, and
      third-party insurers offer various options. The VHA offers additional benefit to
      those who are eligible. Advocacy groups such as the American Association of
      Retired Persons struggle to meet its members' needs and concerns while generating
      income to provide education and other resources. We must work to promote the
      strengths of the elderly population by addressing preventive strategies while
      maintaining functional independence.

PMID- 15561556
TI  - The role of rehabilitation medicine and palliative care in the treatment of
      patients with end-stage disease.
AB  - Rehabilitation medicine and palliative care share many common goals. They strive
      to maximize physical function and emotional well-being to the highest extent
      possible given the nature of the underlying disease process. Many patients with
      end-stage disease experience symptoms and functional losses that diminish their
      quality of life. This article outlines the benefits that active rehabilitation
      therapy can provide to patients in the terminal stages of their disease and some
      of the ethical and practical issues faced in the planning and provision of this
      care.

PMID- 15561557
TI  - Basics of elder law and legal liabilities of negligence and malpractice for
      physicians as they apply to individuals with disabilities.
AB  - This article provides information regarding the issues that physicians face when
      dealing with elderly patients with cognitive deficits. It includes a discussion
      of basic legal terms and concepts that medical personnel should understand,
      various difficulties encountered by patients and families in crisis situations,
      and how the legal system deals with these issues. It concludes with a general
      discussion of the legal liabilities of negligence and malpractice.

PMID- 15561558
TI  - The immune response of white shrimp Litopenaeus vannamei and its susceptibility
      to Vibrio alginolyticus at different salinity levels.
AB  - White shrimp Litopenaeus vannamei held in 25 per thousand seawater were injected
      with TSB-grown Vibrio alginolyticus (1 x 10(4) cfu shrimp(-1)), and then
      transferred to 5, 15, 25 (control) and 35 per thousand. Over 24-96 h, the
      mortality of V. alginolyticus-injected shrimp held in 5 per thousand and 15 per
      thousand was significantly higher than that of shrimp held in 25 per thousand and
      35 per thousand, and the mortality of V. alginolyticus-injected shrimp held in 5
      per thousand was the highest. Shrimp held in 25 per thousand and then transferred
      to 5, 15, 25 (control) and 35 per thousand were examined for THC (total haemocyte
      count), phenoloxidase activity, respiratory burst, superoxide dismutase (SOD)
      activity, phagocytic activity and clearance efficiency to V. alginolyticus after
      12-72 h. The THC, phenoloxidase activity, respiratory burst, SOD activity,
      phagocytic activity and clearance efficiency decreased significantly for the
      shrimp held in 5 and 15 per thousand after 12 h. It is concluded that the shrimp
      transferred from 25 per thousand to low salinity levels (5 and 15 per thousand)
      had reduced immune ability and decreased resistance against V. alginolyticus
      infection.

PMID- 15561559
TI  - Preferential induction of apoptosis in the rainbow trout macrophage cell line,
      RTS11, by actinomycin D, cycloheximide and double stranded RNA.
AB  - The rainbow trout macrophage cell line RTS11 was found to be considerably more
      sensitive than rainbow trout fibroblast (RTG-2) and Chinook salmon epithelial
      (CHSE-214) cell lines to killing by macromolecular synthesis inhibitors,
      actinomycin D (AMD) and cycloheximide (CHX), a synthetic double stranded RNA
      (dsRNA), polyinosinic:polycytidylic acid (poly IC), and combinations of poly IC
      with AMD or CHX. Exposures of 24-30 h to AMD or CHX alone killed RTS11, but not
      CHSE-214 and RTG-2, in basal medium, L-15, with or without fetal bovine serum
      (FBS) supplementation. A two-week exposure to poly IC killed RTS11 in L-15,
      whereas RTG-2 and CHSE-214 remained viable. At concentrations that caused very
      little or no cell death, CHX or AMD pretreatments or co-treatments sensitized
      RTS11 to poly IC, causing death within 30 h. In all cases death was by apoptosis
      as judged by two criteria. H33258 staining revealed a fragmented nuclear
      morphology, and genomic degradation into oligonucleosomal fragments was seen with
      agarose gel electrophoresis. With AMD- or CHX-induced death, killing seemed
      caspase-independent as the pan caspase inhibitor, z-VAD-fmk, failed to block
      killing. By contrast, z-VAD-fmk almost completely abrogated killing by co
      treatments of poly IC and low concentrations of AMD or CHX, suggesting caspase
      dependence. Killing by both types of treatments was blocked by 2 aminopurine (2
      AP), which suggests the involvement of dsRNA-dependent protein kinase (PKR). The
      sensitizing of RTS11 to poly IC killing by AMD or CHX could be explained by a
      decrease in the level of a short-lived anti-apoptotic protein(s) and/or by the
      triggering of a ribotoxic stress.

PMID- 15561560
TI  - Molecular cloning and characterisation of a pattern recognition molecule,
      lipopolysaccharide- and beta-1,3-glucan binding protein (LGBP) from the white
      shrimp Litopenaeus vannamei.
AB  - A lipopolysaccharide- and beta-1,3-glucan binding protein (LGBP) cDNA was cloned
      from the haemocyte and hepatopancreas of white shrimp Litopenaeus vannamei using
      oligonucleotide primers and RT-PCR. Both 3'- and 5'-regions were isolated by
      rapid amplification of cDNA end RACE method. Analysis of nucleotide sequence
      revealed that the cDNA clone has an open reading frame of 1101 bp encoding a
      protein of 367 amino acids including a 17 amino acid signal peptide. The
      calculated molecular mass of the mature proteins (350 amino acids) is 39.92 kDa
      with an estimated pI of 4.37. Two putative integrin binding motifs (cell adhesion
      site), RGD (Arg-Gly-Asp) and a potential recognition motif for beta- (1-->3)
      linkage of polysaccharides were observed in the LGBP. Sequence comparison showed
      that LGBP deduced amino acid of L. vannamei has an overall similarity of 95%, 92%
      and 61% to that of blue shrimp Litopenaeus stylirostris LGBP, tiger shrimp
      Penaeus monodon BGBP and crayfish Pacifastacus leniusculus LGBP, respectively.
      Quantitative real-time RT-PCR analysis showed that LGBP transcript in haemocyte
      of L. vannamei increased in 3- and 6-h post Vibrio alginolyticus injection.

PMID- 15561561
TI  - Short- and long-term effects of a dietary yeast beta-glucan (Macrogard) and
      alginic acid (Ergosan) preparation on immune response in sea bass (Dicentrarchus
      labrax).
AB  - The present study investigated the immunomodulatory activity of Ergosan, an algal
      extract containing alginic acid, and Macrogard, a yeast extract containing beta
      glucans, on innate and specific immunity in sea bass (Dicentrarchus labrax). Four
      cycles of experimental feeding using normal fish feed formulation (control group)
      supplemented with Ergosan (0.5%) or Macrogard (0.1%) were performed at 60-day
      intervals (15 days of treatment+45 days of suspension). Serum complement,
      lysozyme, total proteins and heat shock protein (HSP) concentrations were
      measured at 15, 30 and 45 days from the end of the first 15-day feeding cycle
      (short term) and 45 days after the end of each feeding cycle over a 35-week
      period (long term). The percentage of B- and T-lymphocytes in peripheral blood
      leucocytes and gut were measured over long-term trial. Significant elevation (P <
      0.05) in serum complement activity occurred in sea bass fed with alginic acid and
      glucans, at 15 days from the end of first cycle of treatment. Significant
      elevation (P < 0.05) in serum lysozyme, gill and liver HSP concentration were
      observed in the same experimental groups at 30 days from the end of treatment,
      whereas a significant increase (P < 0.05) of complement activity was only
      observed in fish that received an Ergosan diet. At 45 days from the end of
      treatment, complement, lysozyme and HSP concentration did not differ among
      groups. Over the long-term period, no significant differences were observed in
      innate and specific immune parameters, survival, growth performances and
      conversion index in treated and control fish. A dramatic decrease of both innate
      and acquired immune parameters was observed during the winter season in all
      groups, followed by a partial recovery when water temperature increased.
      Reduction in complement and lysozyme activities was significatively correlated (p
      < 0.01) to water temperature variation. The results suggested the potential of
      alginic acid and beta-glucans to activate some innate immune responses in sea
      bass, and particularly under conditions of immunodepression related to
      environmental stress.

PMID- 15561562
TI  - Stimulation of immunity in Indian major carp Catla catla with herbal feed
      ingredients.
AB  - Catla catla, catla (150 +/- 20 g) were fed a diet containing seed of Achyranthes
      aspera (0.5%) and control diet without A. aspera for four weeks prior to and
      after ip injection with chicken erythrocytes. Fish were sampled for four
      consecutive weeks after immunization. Hemagglutination antibody titers were
      significantly higher in the test group of fishes compared with the control group.
      Serum globulin levels were significantly (P(t-test) < 0.05) higher in the test
      group than control group on days 14 and 21. Anti-trypsin activity due to total
      serum protease inhibitors and alpha1-antiprotease was also significantly (P(t
      test) < 0.05) higher in the test group of fishes than the control. RNA/DNA ratio
      of spleen and kidney was also significantly (P(t-test) < 0.05) higher in test
      group than the control group. All these results confirm that A. aspera enhances
      the immunity of catla.

PMID- 15561563
TI  - Molecular cloning and expression analysis of rainbow trout (Oncorhynchus mykiss)
      interleukin-10 cDNAs.

PMID- 15561564
TI  - Molecular cloning of alpha2- macroglobulin in sea scallop Chlamys farreri
      (Bivalvia, Mollusca).

PMID- 15561565
TI  - Quo vadis: part 1.

PMID- 15561566
TI  - Quo vadis: part 2.

PMID- 15561567
TI  - Assessment of intra- and interobserver variability of pulmonary vein measurements
      from CT angiography.
AB  - RATIONALE AND OBJECTIVES: Pulmonary vein (PV) stenosis is a common complication
      after radiofrequency ablation for atrial fibrillation. This study investigated
      the intra- and interobserver variability and precision of PV ostial measurements
      from three-dimensional computed tomography angiography. MATERIALS AND METHODS:
      Four observers measured the maximum and minimum diameters, as well as area, of
      the four PVs of seven patients who underwent a three-dimensional computed
      tomography scan before radiofrequency ablation. Each observer performed two sets
      of measurements. The intra- and interobserver variability of the measurements was
      calculated using analysis of variance. RESULTS: Intraobserver variability was
      approximately two times lower than interobserver variability in measurements of
      diameter and area. The standard error of the measurement (SEM), SEM(intra) and
      SEM(inter), were lower for the mean diameter than the maximum diameter. The
      minimum detectable changes in diameters, DeltaD(intra) and DeltaD(inter), and
      area, DeltaA(intra) and DeltaA(inter), demonstrated the same statistical trend as
      the corresponding SEM for each of the four veins. Both DeltaD(intra) and
      DeltaD(inter) and DeltaA(intra) and DeltaA(inter) were smaller than the
      corresponding lower bounds of the 95% confidence interval for 50% diameter
      reduction and 75% area reduction. The direct results of DeltaA(intra) and
      DeltaA(inter) for each of the four veins were consistently less than DeltaA's
      calculated from the corresponding DeltaD(intra) and DeltaD(inter). CONCLUSION: PV
      ostial measurements are less variable when made by a single observer than by
      multiple observers, and mean diameter measurements are more precise than a
      single, maximum diameter measurement. Both diameter and area measurements are
      capable of quantifying the mild PV stenosis. Furthermore, area can be measured
      with greater precision than mean diameter and should be used in PV ostium caliber
      determination.

PMID- 15561568
TI  - Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium
      employing doses with equal X-ray attenuation in renal arteriography: an
      experimental study in pigs.
AB  - RATIONALE AND OBJECTIVES: To investigate in a unilaterally nephrectomized porcine
      model whether gadolinium contrast media (Gd-CM) are less nephrotoxic than iodine
      media (I-CM) in x-ray arteriography of a kidney made temporarily ischemic by
      arterial balloon occlusion. MATERIALS AND METHODS: In a noncrossover design, 3 mL
      of each test solution were injected in eight pigs (mean weight 19 kg) at a rate
      of 20 mL/min into the right renal artery at the start of a 10-minute period of
      ischemia. In group 1 (40 pigs) we injected 0.5 M gadopentetate, 0.5 M
      gadodiamide, 0.5 M iohexol (190 mg I/mL), 0.18 M iohexol (70 mg I/mL; with an x
      ray attenuation equal to that of 0.5 M Gd-CM at 80 kV), and saline. In group 2
      (24 pigs), we tested 0.18 M iohexol with ischemia and saline with and without
      ischemia. Gd- and iodine contrast media functioned as markers of glomerular
      filtration rate (GFR). When saline was tested, a low dose of iohexol (3 mL per
      pig; 300 mg I/mL) was injected as GFR marker intravenously in group 1 and into
      the renal artery in group 2. The plasma half-life elimination times of the CM 1-3
      hours after injection were used to compare the effects of the different test
      solutions on GFR. Longer half-life means lower GFR. RESULTS: Group 1: median
      plasma half-life elimination time of the GFR marker was 3 340 minutes after
      injection of 0.5 M gadopentetate, 256 after 0.5 M gadodiamide, 179 after 0.5 M
      iohexol, 143 after 0.18 M iohexol, and 133 minutes after saline. All differences
      except that between 0.18 M iohexol and saline were statistically significant (P <
      .01). Group 2: median plasma half-life was 174 minutes after 0.18 M iohexol with
      ischemia, 196 minutes after saline with ischemia, and 195 minutes after saline
      without ischemia. There were no significant differences between the test
      solutions in group 2 (P > .05). CONCLUSION: In pigs, 0.5 M Gd-CM were more
      nephrotoxic than both equal-attenuating (70 mg I/mL) and equimolar (190 mg I/mL)
      concentrations of the I-CM iohexol. These results do not support the "off-label"
      use of Gd-CM for renal x-ray arteriography in man instead of commercially
      available concentrations of iodine contrast media at 140, 150 and 180 mg I/mL or
      diluted to 70 mg I/mL.

PMID- 15561569
TI  - Autofluorescence spectroscopy in whole organs with a mobile detector system.
AB  - RATIONALE AND OBJECTIVES: Autofluorescence can be exploited to obtain
      spectroscopic information about tissues or organs in a noninvasive fashion. The
      knowledge of normal organ patterns is a prerequisite for subsequent
      characterization of pathological states, eg, inflammation or tumors. Therefore,
      the aim of this study was to investigate the autofluorescence properties of
      healthy organs in mice. MATERIALS AND METHODS: Organs from C57Bl/6 mice were
      removed in toto and stored in physiologic sodium chloride solution on ice (non
      perfused specimens). Investigations were performed with a custom-made mobile
      fluorescence detector. Excitation-emission matrices (EEMs) were measured in
      selected organs (bladder, brain, kidney, liver, and spleen) (n = 5). Afterwards,
      single-emission spectra were obtained in selected organs (bladder, colon, brain,
      kidney, liver, and spleen) and peak fluorescence signal intensities were
      calculated (n = 9). RESULTS: EEMs showed that excitation at wavelengths from 300
      310 nm (emission spectra in all samples of bladder and brain; probably caused by
      collagen/elastin) and from 350-360 nm (emission spectra in all samples with the
      exception of spleen; probably caused by NAD(P)H) seem to be best suited for
      autofluorescence measurements in organs. The single-emission spectra measurements
      were noticeably different in terms of occurrence (yes/no response) and intensity
      of fluorescence emission peaks in different organs. CONCLUSION: Combined
      autofluorescence measurements of collagen/elastin (for structural information)
      and NAD(P)H (for functional information) allow conclusions about the target
      organs. Therefore, autofluorescence measurements seem to be a diagnostic tool
      feasible for characterization of tissue.

PMID- 15561570
TI  - Completion of colorectal cancer screening in women attending screening
      mammography.
AB  - RATIONALE AND OBJECTIVES: The American Cancer Society (ACS) and the United States
      Preventive Services Task Force (USPSTF) recommend colorectal cancer (CRC)
      screening to begin at age 50 in individuals at average risk for CRC. To estimate
      rate at which women eligible for CRC screening at the time of screening
      mammography attendance later completed in CRC screening, we retrospectively
      evaluated CRC screening utilization in women who underwent screening mammography
      at our institution. MATERIALS AND METHODS: We retrospectively identified 3357
      women between the ages of 50 to 75 who received screening mammography in 1998 at
      a single academic medical center using the institution's Radiology Information
      System (RIS). Additional information collected from the institution's Health
      System Data Warehouse and the Radiology department's mammography quality
      assurance data included mammography results, Breast Imaging Reporting and
      Database System (BI-RADS) classification of mammography findings, recommendation
      for screening mammography follow-up, insurance status, and CRC screening
      utilization after screening mammography. After excluding women who were current
      with CRC screening at the time of mammography, we determined the proportion of
      eligible women who completed CRC screening after mammography. Age, insurance
      type, BI-RADS code, and recommendation code were evaluated as potential
      predictors of CRC screening completion in eligible women. RESULTS: Of the 3357
      women between the ages of 50 and 75 who received screening mammography in 1998,
      only 414 (12.3%) were current with CRC screening at the time of screening
      mammography. Of the remaining 2943 women who were eligible for CRC screening at
      the time of screening mammography, 142 (4.8%) subsequently completed CRC
      screening. Average time to completion of CRC screening after screening
      mammography is 35.4 months (range, 0.27-64.9). Managed care insurance was the
      only significant predictor of CRC screening completion after screening
      mammography in eligible women after adjusting for other variables (adjusted OR
      1.73, 95% CI 1.21-2.47, P < .0001). Neither BI-RADS classification nor
      postmammography recommendations were significantly associated with CRC screening
      completion. CONCLUSIONS: Prevalence studies have demonstrated that women who were
      compliant with screening mammography were more compliant with CRC screening. Our
      data suggest that despite this increased compliance, overall incidence of CRC
      screening is low in the screening mammography population.

PMID- 15561571
TI  - Clinical evaluation of a new digitizing device for improved film mammography.
AB  - RATIONALE AND OBJECTIVES: The study was designed to evaluate a new digitizing
      device, the iView (Maxxvision, LLC, Gainesville, FL), which aims to replace the
      magnifying glass in mammography with real-time film digitization, display, and
      processing. MATERIALS AND METHODS: A receiver operating characteristic (ROC)
      experiment was performed with 5 certified mammographers and 114 mammograms that
      were read with and without the iView. A satisfaction survey was also conducted on
      the system's features and usefulness. RESULTS: Data analysis suggested that (1)
      Cancer sensitivity could improve with the use of the iView system. ROC area
      differences showed improvements from 2% to 24% although these were not always
      statistically significant. At a false positive rate of 0.2, the true positive
      rate increased up to 60% depending on the set of cases and the observer's
      experience. (2) Specificity could also be improved. At a true positive rate of
      0.9, the false positive rate decreased by as much as 55%. (3) Most observers felt
      more confident in their decisions when using the iView, although the prototype's
      ergonomic problems did not allow full utilization of its capabilities.
      CONCLUSION: Our pilot clinical study showed that the iView has the potential to
      improve mammogram interpretation. In addition, the system could broaden the
      applicability of electronic information and provide wider access to digital
      technology through a relatively simple and cost-effective approach. Observers
      recommended several improvements in the ergonomics and default display of the
      system that are currently implemented by the company. A larger clinical study of
      the improved system is necessary to clearly demonstrate its clinical value for
      mammography.

PMID- 15561572
TI  - MR and fluorescent imaging of low-density lipoprotein receptors.
AB  - RATIONALE AND OBJECTIVES: Over-expression of low-density lipoprotein receptors
      (LDLRs) occurs in many types of malignancies and is related to the requirement
      for lipids for rapid proliferation of the tumors. On the other hand, LDLRs that
      are unable to bind LDL are found on hepatocytes of patients with familial
      hypercholesterolemia (FH), a genetic disease that leads to premature
      atherosclerosis and death. The highly selective binding of LDL to LDLR makes
      these particles ideal carriers of therapeutic and diagnostic contrast agents into
      the targeted cells. The objectives of this paper are to examine whether a
      prototype contrast agent (PTIR267) with dual detection properties is suitable for
      labeling of LDL particles for in vivo detection of LDLR by magnetic resonance
      imaging (MRI) and for in vitro monitoring of cellular localization by confocal
      fluorescence microscopy. MATERIALS AND METHODS: PTIR267 is a lipophilic GdDTPA
      derivative conjugated to a fluorescent dye. The conjugated dye molecule makes the
      probe sufficiently water soluble to allow labeling of LDL by a brief incubation
      of LDL with PTIR267 dissolved in PBS at 37 degrees C (mole ratio LDL: PTIR267 =
      0.09:1). The molar relaxivity of PTIR267 in saline is 26 mM(-1)s(-1). Specific
      LDLR-mediated uptake of PTIR267-labeled LDL was demonstrated in vitro by confocal
      fluorescence imaging of B16 melanoma cells using confocal fluorescence imaging.
      In vivo uptake of PTIR267-labeled LDL by a subcutaneously implanted B16 melanoma
      in mice leads to 30% decrease in longitudinal relaxation time (T(1)) in the
      tumor. In vivo uptake of PTIR267-labeled LDL leads to 70% decrease in T(1) in a
      normal C57BL/6 mouse liver; however, in the liver of LDL receptor gene knockout
      (LDLr-/-) mice with C57BL/6 background, only 12% decrease in T(1) is observed.
      CONCLUSIONS: The dual fluorescence and MR imaging properties of PTIR267, combined
      with the ease of LDL labeling, suggest that it will be a useful tool for
      optimization of LDLR-targeted cancer diagnosis or therapy and for monitoring the
      efficacy of gene therapy of FH.

PMID- 15561573
TI  - Power estimation for the Dorfman-Berbaum-Metz method.
AB  - RATIONALE AND OBJECTIVES: The authors describe how to perform power and sample
      size computations for the Dorfman-Berbaum-Metz method for analyzing multireader
      receiver operating characteristic (ROC) studies when data from a pilot study or
      from a previous study similar to the planned study are available. MATERIALS AND
      METHODS: Power and sample size computations are described in a step-by-step
      procedure. RESULTS: To illustrate the power computation method we treat 2 studies
      that did not show a significant difference between modalities as pilot studies
      for planning future studies. For the future studies we plan to compare the
      modalities with respect to the mean of the treatment-reader area under the curve
      (AUC) estimates. We show how to estimate the reader and case sample sizes for
      each future study to have 80% power to detect a specified difference in modality
      AUCs. CONCLUSIONS: Application of the power and sample size computation procedure
      for the Dorfman-Berbaum-Metz method is straightforward. For a given effect size
      there will be several different reader and case sample size combinations that
      yield the desired power. It is important that the pilot study or previous study
      used for the computations be comparable to the planned study with respect to the
      modalities, reader expertise, case selection, and ratio of normal to abnormal
      cases.

PMID- 15561574
TI  - A primer on molecular biology for imagers IX. How to become a "molecular imager".

PMID- 15561575
TI  - Lung biopsy with a 12-gauge cutting needle is possible using an insertion sheath
      in animal models.
AB  - RATIONALE AND OBJECTIVES: The volume of lung tumor core biopsy specimens has been
      restricted because of concerns for complications such as bleeding and air
      leakage. In this animal experiment, we investigated the possibility of larger
      bore biopsies through the peripheral lung parenchyma. MATERIALS AND METHODS: Lung
      biopsy was done in male domestic pigs (n= 4) under thoracotomy. A single biopsy
      using a 12-gauge cutting biopsy needle was done with sheath (sheath group, eight
      biopsies) or without sheath (nonsheath group, eight biopsies). After biopsy,
      bleeding time, bleeding amount, and positive airway pressure causing air leakage
      from the insertion site was compared between groups (Mann-Whitney U test). To
      observe long-term effects in closed-chest animals, percutaneous lung biopsy with
      the use of a sheath was carried out percutaneously in male beagles (n = 9). The
      animals were observed for 3 weeks. RESULTS: In the pigs (sheath group) after
      biopsy, bleeding flowed through the sheath and formed a sheath-molded fibrin plug
      that secured the insertion site. Bleeding time and amount decreased significantly
      in the sheath group compared with the nonsheath group (115 +/- 108 versus 295 +/-
      150 seconds, P = .018, and 37 +/- 41 versus 98 +/- 72 grams, P= .027,
      respectively). Air leakage pressure was significantly higher in the sheath group
      compared with the nonsheath group (37 +/- 6 versus 18 +/- 5 cmH2O, P = .001). In
      the beagles, no complications such as pneumothorax, hemothorax, or airway
      bleeding was apparent. CONCLUSION: Although we have not evaluated lung tumor
      biopsy per se, lung tumor biopsy with a 12-gauge cutting needle may be possible
      with a use of a sheath.

PMID- 15561576
TI  - Sagittal reformations of volumetric inspiratory and expiratory high-resolution CT
      of the lung.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to determine whether
      sagittal reformations of volumetric high-resolution computed tomography (CT)
      provide additional information in evaluating lung abnormalities compared to axial
      high-resolution CT images. MATERIALS AND METHODS: Twenty-two consecutive patients
      who underwent combined inspiratory and expiratory volumetric high-resolution CT
      from May to July 2003 were studied. Using end-inspiratory and end-expiratory
      sagittal reformatted images, respiratory motion artifacts were evaluated at
      upper, middle, and lower lung areas bilaterally. Diaphragmatic motion artifacts
      were evaluated bilaterally. The detection of major and minor fissures was
      assessed. Additional findings on sagittal reformations were graded using a three
      point scale: grade 1 = no additional findings; grade 2 = additional findings of
      no diagnostic significance; grade 3 = additional findings of diagnostic
      significance. RESULTS: Respiratory motion artifacts were either imperceptible or
      present but not diagnostically limiting except for one case, in which
      diagnostically limiting image degradation was noted in the bilateral lower lung
      areas. Diaphragmatic motion artifacts were frequently present: 95% (21/22) at end
      inspiration, and 86% (19/22) at end-expiration; however, diagnostically limiting
      artifacts were observed in only two cases. The grading of additional findings on
      sagittal reformatted images was statistically significant (grade 1, n = 13; grade
      2, n = 7; grade 3, n = 2; median, 1; P = .004) compared to axial images.
      Additional findings included relationship between mass/nodules and
      fissure/pleura/pericardium (grade 2, n = 4; grade 3, n = 2), distribution of
      interstitial abnormalities of the lung (grade 2, n = 2), and diaphragmatic
      eventration (grade 2, n = 1). CONCLUSION: Sagittal reformatted images of
      volumetric high-resolution CT provided additional information compared to
      volumetric axial images alone with statistical significance.

PMID- 15561577
TI  - Rapid wireless transmission of head CT images to a personal digital assistant for
      remote consultation.
AB  - RATIONALE AND OBJECTIVES: We describe a simple technique for transmission of a
      complete set of cranial computed tomography (CT) images to a commercially
      available wireless personal digital assistant (PDA) for remote teleradiology
      consultation. MATERIALS AND METHODS: A complete set of images from the head CT of
      a trauma patient with subdural hematoma (19 images) was captured from a picture
      archiving and communication system and transmitted wirelessly as an e-mail
      attachment after being compressed. The images were retrieved, decompressed, and
      reviewed using commercially available software and a PDA with cellular phone
      capability. RESULTS: A complete head CT was transmitted to a remote radiologist's
      wireless PDA for consultation. The entire procedure (including image capture,
      transmission, and review) took approximately 11.5 minutes. CONCLUSION: Using the
      technique described in this article the wireless PDA may function as a robust
      medium for facilitating care of brain trauma patients by allowing rapid access to
      trauma radiologists or neurosurgeons.

PMID- 15561578
TI  - Quantification of clinical consultations in academic emergency radiology.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to quantify the impact of
      clinical consultation on the workload of an academic emergency radiology section.
      MATERIALS AND METHODS: Data from a 7-day audit (24 h/d) of the number and length
      of clinical consultations was expressed as the mean number of consultations per
      24 hours and consultation minutes per 24 hours. Consultations performed on images
      acquired from outside institutions were noted. The attending radiologist
      consultation fraction was defined as the attending consultation minutes per 24
      hours divided by the number of minutes of attending coverage per 24 hours. Using
      annualized work relative value units per full-time employee (wRVU/FTE) over the 7
      days, the consultation value unit per full-time employee (CVU/FTE) was defined
      and calculated as the consultation fraction multiplied by the annual wRVU/FTE.
      RESULTS: For the attending radiologists, the consultation fraction was 0.13 and
      the CVU/FTE was 1216. Twenty-two percent of the total consultation minutes were
      spent on studies performed outside our institution. CONCLUSIONS: Clinical
      consultation represents a significant portion of the workload in academic
      emergency radiology. The consultation fraction describes the fraction of the
      radiologist's time spent in consultation, and the CVU/FTE expresses the workload
      of clinical consultations in terms of wRVU/FTE, the factor used most commonly to
      determine the academic radiologist's productivity and staffing.

PMID- 15561579
TI  - Quantification of clinical consultations in academic emergency radiology:
      Counterpoint.

PMID- 15561580
TI  - Reinventing the apprenticeship: the hot seat in the digital era.
AB  - RATIONALE AND OBJECTIVES: Describe new interactive digital teaching methods for
      medical student education in radiology and evaluate student responses. MATERIALS
      AND METHODS: Third- and fourth-year medical students on radiology clerkship were
      taught using either film-based "hot seat" format, digital "hot seat," or didactic
      slide-based format. Digital hot seat included direct projection of full
      resolution images and use of digital tablet for annotation. Students completed
      surveys commenting on each method. RESULTS: Before 2003-2004, comments were
      available from general course surveys. Only positive responses were made
      regarding digital hot seat format. Dedicated surveys of teaching methods since
      July 2003 (23 students) showed 100% gave high ratings to digital hot seat methods
      (1 or 2 on a scale from 1 to 5), citing easier visibility of findings and ability
      to draw on images as positive features. Fifty-two percent rated film hot seat
      method <3, with limited visibility as the main complaint. Didactic slide teaching
      was rated <3 by 74%. Eighty-three percent chose digital hot seat as their
      favorite format overall. CONCLUSIONS: Students overwhelmingly favor digital hot
      seat teaching over film-based or didactic slide presentations. Digital hot seat
      methods preserve the best features of case-based interactive teaching while
      improving visibility of findings.

PMID- 15561581
TI  - Management education during radiology residency: development of an educational
      practice.
AB  - The practice of radiology has dramatically increased in complexity, largely due
      to three broad influences. These include the proliferation of imaging
      technologies, the economic pressures to limit healthcare costs, and the
      increasingly intrusive role of third parties (whether payors, regulators, or
      government) in everyday healthcare transactions. Practicing radiologists have
      been adapting to these technologic and socioeconomic changes and will continue to
      do so by managing the quality and scope of their professional services, the
      workflow of radiology operations, and the economic viability of their practices.
      It is likely that radiology practices would benefit from the presence of one or
      more radiologists with managerial training and skills. In this article, it is
      proposed that management education for radiologists may actually be initiated
      during residency; the value and the experiences with such an educational practice
      are described.

PMID- 15561582
TI  - Regulation of cell-cell adhesion.

PMID- 15561583
TI  - Regulation of cell-cell adhesion during Dictyostelium development.
AB  - During development of Dictyostelium, four adhesion systems have been identified
      and adherens junction-like structures have been discovered in the fruiting body.
      The temporal and spatial expression of cell adhesion molecules (CAMs) is under
      stringent developmental control, corresponding to major shifts in morphological
      complexity. Genetic manipulations, including over-expression and knockout
      mutations, of the adhesion genes, cadA (encoding DdCAD-1), csaA (gp80) and lagC
      (gp150), have shed light on new roles for cell adhesion molecules in aggregate
      size regulation, cell-type proportioning, cell differentiation and cell sorting.
      As cell-cell interactions remain highly dynamic within cell streams and
      aggregates, mechanisms must exist to facilitate the rapid assembly and
      disassembly of adhesion complexes. Studies on gp80 have led to a model for the
      rapid assembly of adhesion complexes via lipid rafts.

PMID- 15561584
TI  - Roles and modes of action of nectins in cell-cell adhesion.
AB  - Nectins are Ca(2+)-independent immunoglobulin (Ig)-like cell-cell adhesion
      molecules (CAMs), which comprise a family consisting of four members. Each nectin
      homophilically and heterophilically trans-interacts and causes cell-cell
      adhesion. Biochemical, cell biological, and knockout mice studies have revealed
      that nectins play important roles in formation of many types of cell-cell
      junctions and cell-cell contacts, including cadherin-based adherens junctions
      (AJs) and synapses. Mode of action of nectins in the formation of AJs has
      extensively been investigated. Nectins form initial cell-cell adhesion and
      recruit E-cadherin to the nectin-based cell-cell adhesion sites. In addition,
      nectins induce activation of Cdc42 and Rac small G proteins, which eventually
      enhances the formation of cadherin-based AJs through the reorganization of the
      actin cytoskeleton. Nectins furthermore heterophilically trans-interact with
      nectin-like molecules (Necls), other Ig-like CAMs, and assist or modify their
      various functions, such as cell adhesion, migration, and proliferation. We
      describe here the roles and modes of action of nectins as CAMs.

PMID- 15561585
TI  - Regulation of cadherin stability and turnover by p120ctn: implications in disease
      and cancer.
AB  - The strength of cadherin based cell-cell adhesion is modulated by signaling
      events that control the amount of cadherin present at the cell surface, and the
      clustering of cadherins into strong adhesive junctions. p120ctn has been
      indirectly implicated in clustering for some time, but it now appears that its
      main function is to regulate cadherin turnover. Forced p120 downregulation (e.g.,
      by siRNA targeting) results in a striking dose-dependant loss of endogenous
      cadherins, indicating that p120 is essential for cadherin stability. These data
      challenge some important paradigms and suggest novel interpretations of existing
      data. For example, most of the effects of DN-cadherin expression can be accounted
      for by sequestration of p120. Thus, DN-cadherins phenocopy p120-downregulation,
      and a significant literature exists already that suggests consequences of p120
      deficiency in disease and cancer. Moreover, p120 downregulation occurs frequently
      in essentially all of the major carcinoma types. Thus, it is possible that the
      classic observation of E-cadherin-deficiency in metastatic cancer may in some
      cases be due to p120 downregulation rather than better understood mechanisms
      acting at the level of E-cadherin transcription.

PMID- 15561586
TI  - Regulation of desmosome assembly and adhesion.
AB  - Desmosomes are highly organized intercellular junctions that provide mechanical
      integrity to tissues by anchoring intermediate filaments to sites of strong
      adhesion. Transcriptional regulation of desmosomal cadherins specifies their
      expression pattern and assembly into junctions of distinct composition, thus
      tailoring desmosome functions in adhesion and morphogenesis within different
      cells and complex tissues. Desmosome assembly and disassembly are regulated post
      translationally by calcium, kinase/phosphatase activity, proteolytic processing,
      and cross talk with adherens junctions. Post-translational events also govern the
      level of non-junctional forms of plakoglobin and plakophilins. These armadillo
      proteins participate in various nuclear functions, in some cases transducing
      signals regulating cell growth and differentiation.

PMID- 15561587
TI  - Phagocytosis, an alternative model system for the study of cell adhesion.
AB  - Cell adhesion encompasses a variety of cell-cell and cell-matrix adhesive
      interactions. Whereas ligation of most adhesion receptors activate Rho-family GTP
      binding proteins and the subsequent reorganization of the actin cytoskeleton, the
      molecular mechanisms involved remain poorly understood. Because phagocytosis is a
      spatially restricted adhesion process, it represents a simplified model system to
      investigate the spatio-temporal regulation of the signalling pathways that link
      surface adhesion receptors, small GTPases and the actin cytoskeleton. This review
      highlights some of the similarities between the formation and maintenance of
      adhesive contacts and phagocytic uptake and discusses why the study of
      phagocytosis can help understand more complex adhesion processes.

PMID- 15561589
TI  - Integrative bioinformatics for functional genome annotation: trawling for G
      protein-coupled receptors.
AB  - G protein-coupled receptors (GPCR) are amongst the best studied and most
      functionally diverse types of cell-surface protein. The importance of GPCRs as
      mediates or cell function and organismal developmental underlies their
      involvement in key physiological roles and their prominence as targets for
      pharmacological therapeutics. In this review, we highlight the requirement for
      integrated protocols which underline the different perspectives offered by
      different sequence analysis methods. BLAST and FastA offer broad brush strokes.
      Motif-based search methods add the fine detail. Structural modelling offers
      another perspective which allows us to elucidate the physicochemical properties
      that underlie ligand binding. Together, these different views provide a more
      informative and a more detailed picture of GPCR structure and function. Many
      GPCRs remain orphan receptors with no identified ligand, yet as computer-driven
      functional genomics starts to elaborate their functions, a new understanding of
      their roles in cell and developmental biology will follow.

PMID- 15561590
TI  - Design and analysis of experiments with high throughput biological assay data.
AB  - The design and analysis of experiments using gene expression microarrays is a
      topic of considerable current research, and work is beginning to appear on the
      analysis of proteomics and metabolomics data by mass spectrometry and NMR
      spectroscopy. The literature in this area is evolving rapidly, and commercial
      software for analysis of array or proteomics data is rarely up to date, and is
      essentially nonexistent for metabolomics data. In this paper, I review some of
      the issues that should concern any biologists planning to use such high
      throughput biological assay data in an experimental investigation. Technical
      details are kept to a minimum, and may be found in the referenced literature, as
      well as in the many excellent papers which space limitations prevent my
      describing. There are usually a number of viable options for design and analysis
      of such experiments, but unfortunately, there are even more non-viable ones that
      have been used even in the published literature. This is an area in which up-to
      date knowledge of the literature is indispensable for efficient and effective
      design and analysis of these experiments. In general, we concentrate on
      relatively simple analyses, often focusing on identifying differentially
      expressed genes and the comparable issues in mass spectrometry and NMR
      spectroscopy (consistent differences in peak heights or areas for example).
      Complex multivariate and pattern recognition methods also need much attention,
      but the issues we describe in this paper must be dealt with first. The literature
      on analysis of proteomics and metabolomics data is as yet sparse, so the main
      focus of this paper will be on methods devised for analysis of gene expression
      data that generalize to proteomics and metabolomics, with some specific comments
      near the end on analysis of metabolomics data by mass spectrometry and NMR
      spectroscopy.

PMID- 15561591
TI  - Identification and analysis of cis-regulatory elements in development using
      comparative genomics with the pufferfish, Fugu rubripes.
AB  - The control of vertebrate development is facilitated by cis-regulatory sequences
      hardwired into the genome. Given that many developmental processes are strikingly
      similar across all backboned animals, it is reasonable to expect these sequences
      to be conserved at the nucleotide level, their potential for mutation being
      constrained by their function. Comparison between the genomes of highly divergent
      organisms allows such sequences to be identified and some of the most successful
      approaches have compared regions from the pufferfish, Fugu rubripes, with its
      distant mammalian relatives, rodents and humans. This review describes progress
      made in this kind of comparison, from small regions of individual genes, to whole
      genome alignments.

PMID- 15561592
TI  - Bioinformatics: harvesting information for plant and crop science.
AB  - Bioinformatics is an integral aspect of plant and crop science research.
      Developments in data management and analytical software are reviewed with an
      emphasis on applications in functional genomics. This includes information
      resources for Arabidopsis and crop species, and tools available for analysis and
      visualisation of comparative genomic data. Approaches used to explore
      relationships between plant genes and expressed sequences are compared, including
      use of ontologies. The impact of bioinformatics in forward and reverse genetics
      is described, together with the potential from data mining. The role of
      bioinformatics is explored in the wider context of plant and crop science.

PMID- 15561593
TI  - [Management of soft tissue sarcomas in first isolated local recurrence: a
      retrospective study of 83 cases].
AB  - PURPOSE: To analyse the management and clinical outcome of patients treated for a
      first isolated local recurrence of soft tissue sarcoma (trunk or extremities) and
      to identify prognosis factors. PATIENTS AND MATERIAL: This is a retrospective
      study of 83 adult patients treated between 1980 and 1999. Mean tumor size was 6
      cm. Most sarcomas were located in extremities (N =74), were deep (N =60), and
      proximal (N =53). Thirty involved nerves or vessels. Histologic subtypes were
      mainly grade 2 (42%) or 3 (36%) histocytofibrosarcomas (49%) and liposarcomas
      (20%). Surgical treatment of recurrences consisted in wide excision (32 cases),
      marginal resection (46 cases), five patients requiring amputation. Final results
      were R0 (N =33), R1 (N =47) or R2 (N =3) resection. Beside surgery, six patients
      received neoadjuvant and seven others adjuvant chemotherapy. Twenty-three
      patients received postoperative external beam radiotherapy (EBRT) (mean dose 55
      Gy) and 26 interstitial (192)Ir low dose rate brachytherapy (BCT) (mean dose 45
      Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re
      irradiated. RESULTS: Mean follow up was 59 months. Thirty-seven (45%) tumors
      relapsed, 62% locally as first event. Nineteen patients developed secondary
      distant metastases. Multivariate analysis showed only tumour depth (P =0.05) and
      re-resection for primary R1 resection for the recurrence (P =0.018) being
      independent prognosis factors for tumour control, radiotherapy (EBRT and/or BCT)
      being significant in univariate analysis (P =0.05). Overall survival rate was 73,
      54, and 47% at respectively 3, 5 and 10 years, and was 65, 35 and 32% after a
      further local recurrence. Multivariate analysis showed trunk (P =0.0001) or
      inferior extremity locations (P =0.023), symptomatic (P =0.001), high grade (P
      =0.01), deep (P = 0.01) tumours, and the occurrence of a further local failure (P
      =0.004) as unfavourable characteristics for overall survival. CONCLUSION: Because
      of the high relapse rate in this series, a first isolated local recurrence of STS
      increases mainly the risk of a subsequent local relapse. Quality of local
      treatment for the first local relapse is decisive. When a conservative treatment
      is feasible, it should combine surgical resection and radiotherapy, brachytherapy
      being the best suited in previously irradiated patients. Efforts have to be
      pursued to increase quality of the treatment of primary tumours, at best
      performed in centers that have expertise in this field.

PMID- 15561594
TI  - Conservative treatment of early glottic carcinomas with exclusive radiotherapy.
AB  - BACKGROUND: Early glottic carcinomas can be treated with radiotherapy or surgery
      with similar local control rates but with better functional results with
      radiotherapy. The aim of this study was to analyze the results of our experience
      of exclusive radiotherapy. PATIENTS AND METHODS: From 1975 to 2001, 155 patients
      with Tis, T1 and T2 glottic carcinomas were treated with exclusive radiotherapy.
      Prognostic factors of survival, local control and larynx-preservation rates were
      analyzed in uni and multivariate analyses. RESULTS: Median prescribed dose was 65
      Gy in 44 days. Overall survival was 75% for the whole group, 75% for Tis, 85% for
      T1a, 72% for T1b, 59% for T2. Specific survival was 88% for the whole group, 75%
      for Tis, 94% for T1a, 90% for T1b, 69% for T2. Disease-free survival was 68% for
      the whole group, 75% for Tis, 77% for T1a, 51% for T1b, 58% for T2. Laryngeal
      preservation rate was 85% (133/155). Twenty-nine (29/155, 18%) patients developed
      a local relapse within 31 months. Out of the 10/86 (12%) T1a-Tis relapses, 7/10
      patients underwent total laryngectomy and 79/86 larynx were preserved (92%). Out
      of the 8/22 (36%) T1b relapses, 4/8 patients underwent total laryngectomy. Out of
      the 11/47 (23%) T2 relapses, 8/11 patients underwent total laryngectomy.
      Increased overall treatment time, tumor stage, sub-glottis extension were
      associated with poorer local control. Second malignancies remain a major problem
      in the outcome of this population. CONCLUSION: Radiotherapy remains an efficient
      option in the treatment of early glottic carcinomas providing a high local
      control rate with excellent functional results in laryngectomy-free patients.
      This strategy should be discussed according to the tumor stage, feasibility of
      conservative surgery and patient's preferences.

PMID- 15561595
TI  - The influence of small bowel motion on both a conventional three-field and
      intensity modulated radiation therapy (IMRT) for rectal cancer.
AB  - PURPOSE: To investigate the reduction of irradiated small bowel volume with
      intensity modulated radiation therapy (IMRT) planning in rectal cancer and to
      asses the variability of the irradiated small bowel in the conventional planning
      as in the IMRT planning (IMPlan) by obtaining weekly CT scans. PATIENTS AND
      MATERIALS: Twelve patients with rectal cancer had treatment planning CT scans of
      the pelvis with small bowel contrast obtained for planning and once a week during
      treatment (65 CT scans total). The scans were registered using the bony
      structures. The clinical target volume (CTV), small bowel, large bowel and
      bladder were outlined on each slice. The first CT scan was used for IMPlan and
      conventional three-field planning (ConPlan), which were then applied to the CT
      scans obtained during therapy. RESULTS: The median value among patients of the
      mean volume over a patient's scan of small bowel irradiated > or =95% was 112 cm3
      (standard deviation (SD): 31 cm3) for the ConPlan and 42 cm3 (SD: 17 cm3) for the
      IMPlan. The median total bladder volume was 148 cm3 (SD: 130 cm3). There was a
      good correlation between the volume of irradiated small bowel and the bladder
      volume for IMPlan with <50 cm3 irradiated small bowel and ConPlan with <150 cm3
      (p = 0.002). CONCLUSION: The use of IMRT led to a potentially clinically
      meaningful reduction in the volume of small bowel irradiated, even when
      accounting for small bowel motion. A full bladder was of greatest benefit in
      individuals with the smallest volume of small bowel in the treatment field.

PMID- 15561596
TI  - [Dosimetric validation of compensator for their use in clinical routine, in
      conformation radiotherapy].
AB  - PURPOSE: The aim of this work was to establish the acquisition, calculation and
      3D compensator manufacturing optimum parameters. This methodology is based on
      virtual simulation and 3D dosimetry. MATERIALS AND METHODS: The material used is
      a helicoidal CT (PQ 5000-Marconi), a virtual simulation system (AcQsim version 4
      Marconi), a Treatment Planning System (Dosigray), a linear accelerator Saturne 43
      (Varian, CGR), an automated milling system for compensator filters (Autimo 2.5 D
      HEK), a water tank phantom (wellhofer) and an homogeneous phantom with simple
      patterns in order to simulate the obliquity surface of patient body. The
      compensator was composed by granulate tin because this material ensures a good
      profile modulation. The compensation plane has been calculated at 80% to dose
      profile. The compensator thickness profile has been calculated with different
      acquisition (slice thickness, pitch factor), calculation (attenuation
      coefficient, bixel) and fabrication parameters (drill diameter, specification of
      milling system). RESULTS: After this preliminary study, we have defined the
      optimum parameters for the compensator realization. We have observed that the
      slice thickness, bixel size and drill diameter are the parameters that mainly
      affect the profiles homogeneity. The choice of parameters with smaller dimensions
      S = 3 mm; B = 3 mm, F = 3 mm, improve the profiles homogeneity. Though, for
      manufacture times compatible with the clinical routine, the selected parameters
      are S = 5 mm, B = 6 mm and F = 6 mm. Compensator can be used for any type of
      Linac. However, one must pay attention on their realization and their positioning
      on the beam central axis.

PMID- 15561597
TI  - [Biomodulation of transcriptional factor NF-kappa B by ionizing radiation].
AB  - NF-kappaB (Nuclear Factor-kappaB) was described for the first time in 1986 as a
      nuclear protein binding to the kappa immunoglobulin-light chain enhancer. Since
      then, NF-kappaB has emerged as an ubiquitous factor involved in the regulation of
      numerous important processes as diverse as immune and inflammatory responses,
      apoptosis and cell proliferation. These last two properties explain the
      implication of NF-kappaB in the tumorigenic process as well as the promise of a
      targeted therapeutic intervention. This review focuses on the current knowledge
      on NF-kappaB regulation and discusses the therapeutic potential of targeting NF
      kappaB in cancer in particular during radiotherapy.

PMID- 15561598
TI  - [Clinical practice guidelines: 2004 Standards, Options and Recommendations for
      the management of patient with adenocarcinoma of the stomach--radiotherapy].
AB  - CONTEXT: "The Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of French Cancer Centers
      (FNCLCC), the 20 French regional cancer centers, and specialists from French
      Public Universities, General Hospitals and Private Clinics. The main objective is
      the development of clinical practice guidelines to improve the quality of health
      care and the outcome of cancer patients. OBJECTIVES: To elaborate clinical
      practice guidelines for patients with stomach adenocarcinoma. These
      recommendations cover the diagnosis, treatment and follow-up of these tumors.
      METHODS: The methodology is based on a literature review and critical appraisal
      by a multidisciplinary group of experts, with feedback from specialists in cancer
      care delivery. The Standards, Options and Recommendations are thus based on the
      best available evidence and expert agreement. RESULTS: Adjuvant radiation therapy
      alone is not a standard treatment for patients with stomach adenocarcinoma.
      Adjuvant concomitant chemoradiotherapy is not a standard treatment for patients
      with stage II or III stomach adenocarcinoma R0, with Dl or D2 lymphadenectomy who
      have undergone surgery. Following surgical resection, adjuvant concomitant
      chemoradiotherapy should be proposed to patients without denutrition with a
      lymphadenectomy < Dl (fewer than 15 lymph nodes examined) and those with T3
      and/or N+ tumours following the protocol used in the MacDonald trials (SWOG-9008)
      (Level of evidence B1). Adjuvant concomitant chemoradiotherapy can be
      administered to patients without denutrition with DI or D2 lymphadenectomy and
      with involvement of regional lymph nodes (N2 or N3).

PMID- 15561599
TI  - Nerve growth factor involvement in the visual system: implications in allergic
      and neurodegenerative diseases.
AB  - The purpose of this review is to outline the main role of nerve growth factor
      (NGF) in the visual system and particularly in the ocular surface in
      physiological and pathological conditions. The present review of experimental and
      clinical studies will highlight old and recent strategies for treating ocular
      surface and tear disorders with NGF.

PMID- 15561600
TI  - The role of ephrins and Eph receptors in cancer.
AB  - Eph receptors are the largest receptor tyrosine kinase family of transmembrane
      proteins with an extracellular domain capable of recognizing signals from the
      cells' environment and influencing cell-cell interaction and cell migration.
      Ephrins are the ligands to Eph receptors and stimulate bi-directional signaling
      of the Eph/ephrin axis. Eph receptor and ephrin overexpression can result in
      tumorigenesis as related to tumor growth and survival and is associated with
      angiogenesis and metastasis in many types of human cancer. Recent data suggest
      that Eph/ephrin signaling could play an important role in the development of
      novel inhibition strategies and cancer treatments to potentially target this
      receptor tyrosine kinase and/or its ligand. A deeper understanding of the
      molecular basis for normal versus defective cell-cell interaction through the
      Eph/ephrin axis will enable the potential development of novel cancer treatments.
      This review emphasizes the biology of Eph/ephrin as well as the potential for
      novel targeted therapy through this pathway.

PMID- 15561601
TI  - STATs as critical mediators of signal transduction and transcription: lessons
      learned from STAT5.
AB  - Signal transducers and activators of transcription (Stats) comprise a family of
      seven transcription factors that are activated by a variety of cytokines,
      hormones and growth factors. Stats are activated through tyrosine
      phosphorylation, mainly by Jak kinases, that lead to their dimerization, nuclear
      translocation and regulation of target gene expression. Stat5 was originally
      identified as a transcription factor that regulates the beta-casein gene in
      response to prolactin (PRL), but Stat5 is activated also by several other
      cytokines and growth factors. The molecular mechanisms that underlie Stat5
      mediated transcription involve interactions and cooperation with sequence
      specific transcription factors and transcriptional coregulators. Our studies
      identified p100 protein as a coactivator for Stat5, and suggest the existence of
      a positive regulatory loop in PRL-induced transcription, where PRL stabilizes
      p100 protein, which in turn can cooperate with Stat5 in transcriptional
      activation. Suppressors of cytokine signaling (SOCS) proteins are important
      negative regulators of Stats. A target gene for Stat5, the serine/threonine
      kinase Pim-1, was found to cooperate with SOCS-1 and SOCS-3 to inhibit Stat5
      activity suggesting that Pim-1 together with SOCS-1 and SOCS-3 are components of
      a negative feedback mechanism that allows Stat5 to regulate its own activation.

PMID- 15561602
TI  - The molecular triad OPG/RANK/RANKL: involvement in the orchestration of
      pathophysiological bone remodeling.
AB  - The past decade has seen an explosion in the field of bone biology. The area of
      bone biology over this period of time has been marked by a number of key
      discoveries that have opened up entirely new areas for investigation. The recent
      identification of the receptor activator of nuclear factor kappaB ligand (RANKL),
      its cognate receptor RANK, and its decoy receptor osteoprotegerin (OPG) has led
      to a new molecular perspective on osteoclast biology and bone homeostasis.
      Specifically, the interaction between RANKL and RANK has been shown to be
      required for osteoclast differentiation. The third protagonist, OPG, acts as a
      soluble receptor antagonist for RANKL that prevents it from binding to and
      activating RANK. Any dysregulation of their respective expression leads to
      pathological conditions such as bone tumor-associated osteolysis, immune disease,
      or cardiovascular pathology. In this context, the OPG/RANK/RANKL triad opens
      novel therapeutic areas in diseases characterized by excessive bone resorption.
      The present article is an update and extension of an earlier review published by
      Kwan Tat et al. [Kwan Tat S, Padrines M, Theoleyre S, Heymann D, Fortun Y. IL-6,
      RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology.
      Cytokine Growth Factor Rev 2004;15:49-60].

PMID- 15561604
TI  - Tunable diode laser spectrometer for pulsed supersonic jets: application to
      weakly-bound complexes and clusters.
AB  - The design and operation of an apparatus for studying infrared spectra of weakly
      bound complexes is described in detail. A pulsed supersonic jet expansion is
      probed using a tunable Pb-salt diode laser spectrometer operated in a rapid-scan
      mode. The jet may be fitted with either pinhole or slit shaped nozzles, the
      former giving lower effective rotational temperatures, and the latter giving
      sharper spectral lines. Notable features of the apparatus include use of a
      toroidal multi-pass mirror system to give over 100 passes of the laser through
      the supersonic jet, use of the normal laser controller for laser sweeping during
      both setup and data acquisition, and use of a simple semi-automated wavenumber
      calibration procedure. Performance of the apparatus is illustrated with observed
      spectra of the van der Waals complex He-OCS, and the seeded helium clusters He(N)
      OCS and He(N)-CO.

PMID- 15561605
TI  - DFB laser diodes in the wavelength range from 760 nm to 2.5 microm.
AB  - We present a novel device technology to produce DFB laser diodes which are
      suitable for tunable diode laser spectroscopy. The new technological approach
      employs lateral metal distributed feedback (DFB) gratings in close proximity to
      the laser ridge which results in single mode emission with high spectral purity
      and output powers as required for most spectroscopic applications. Over the
      entire wavelength range from the visible (760 nm) up to the near-infrared (2.5
      microm) single mode emission can be obtained for devices based on different
      semiconductor systems such as GaAs, InP and GaSb. Typical side mode suppression
      ratios are better than 35 dB for cw-room temperature operation and narrow
      linewidths ensure high spectroscopic resolution.

PMID- 15561606
TI  - Line profile study with tunable diode laser spectrometers.
AB  - In this paper, we present the different theoretical line profiles, which can be
      used to describe a shape of molecular transitions in dilute gases: the Voigt,
      Galatry, Rautian and speed dependence models. We discuss their limitations and
      their advantages, and present for illustration different comparisons of model
      results with experimental data obtained with several diode laser spectrometers
      suitable for precise line shape measurements.

PMID- 15561607
TI  - Ammonia monitoring at trace level using photoacoustic spectroscopy in industrial
      and environmental applications.
AB  - An ammonia traces analyser based on photoacoustic spectroscopy is described. The
      system uses a CO(2) laser and a properly designed resonant photoacoustic cell to
      achieve ammonia detection at sub-parts-per-billion (ppb) level. The instrument
      features unattended automatic on-line monitoring of ammonia with a detection
      limit of 0.1 ppb. Interferences from atmospheric CO(2) and H(2)O are efficiently
      suppressed by a careful selection of the laser wavelength and a compensation of
      the water vapour signal made with a high-precision hygrometer. The cell design
      enables continuous measurement at high flow rates (up to 5 l/min), which
      guarantees a fast response time of the system for the monitoring of ammonia, a
      sticky polar molecule that adheres to most surfaces. Various examples of
      applications of the instrument in the semiconductor industry and for atmospheric
      pollution monitoring are presented. They demonstrate the excellent performances
      of the system and its suitability for these applications.

PMID- 15561608
TI  - VCSEL based detection of water vapor near 940nm.
AB  - A vertical-cavity surface-emitting laser (VCSEL) was used to study the absorption
      spectrum of water vapor in the 940nm region. Measurements were performed in
      ambient air at room temperature and in a hydrogen-oxygen flame over the
      temperature range of 1500-1800K. Several rotational absorption lines within the
      2v1 + v3 vibrational band were measured. The absorption spectra were well
      resolved, which demonstrates the feasibility of VCSEL-based spectroscopic
      measurements of water vapor at room and high-temperature in this spectral region.
      The results were in good agreement with the values obtained from the HITRAN-96
      database.

PMID- 15561609
TI  - Near-infrared diode laser spectroscopy of free radicals.
AB  - Spectroscopic results on the radicals HCSi, CCO, and FeC obtained by studying in
      detail energy level structures using 0.8 microm diode laser system are reported.
      Of these radicals, the CCO radical was investigated mainly using Fabry-Perot type
      diode lasers with inconvenient mode gaps in the early stage of our near-infrared
      diode laser spectroscopic study of free radicals, and on the other hand, the FeC
      and HCSi radicals were studied using an external cavity diode laser. For the FeC
      radical, which is an interesting radical composed of an iron atom having 3d
      electrons, information on spin-orbit interaction between the triplet electronic
      ground state and a low-lying singlet electronic excited state is reported
      somewhat in detail. For the HCSi and CCO radicals, spectral particularities
      produced by a Renner-Teller interaction and a spin-orbit interaction are
      described for their high-resolution spectroscopic interest.

PMID- 15561610
TI  - Preliminary results of heterodyne detection with quantum-cascade lasers in the 9
      microm region.
AB  - In this paper, we describe recent results in mid-infrared heterodyne detection
      using quantum-cascade (QC) lasers as local oscillator (LO). In the 9 microm
      range, the heterodyne detection technique was first developed with CO(2) lasers
      and then with Pb-salt diode lasers. Quantum-cascade lasers are promising high
      quality tunable mid-infrared sources. We developed a quantum-cascade laser based
      heterodyne spectrometer. Atmospheric absorption spectra of ozone are presented.

PMID- 15561611
TI  - A compact NIR fiber-optic diode laser spectrometer for CO and CO(2): analysis of
      observed 2f wavelength modulation spectroscopy line shapes.
AB  - A compact fiber-optic diode laser spectrometer for the measurement of CO and
      CO(2) gas concentrations in the near infrared around 1580 nm is described. By use
      of a balanced receiver to suppress diode laser intensity noise a sensitivity of
      6.4 x 10(-7) at 1 Hz system bandwidth was achieved. At a reduced pressure of 80
      hPa this equals to a detection limit of 5.1 ppm CO and 9.1 ppm CO(2) with 1m
      absorption path length. The observed line shapes of the 2f wavelength modulation
      spectroscopy (WMS) scheme are analyzed theoretically and experimentally. Accurate
      measurements of magnitude and phase of the diode laser frequency and intensity
      modulation responses were found critically for modeling the observed line shapes.
      In situ measurements of gas dissociation processes inside of a medium-power
      carbon dioxide laser are presented as an application example.

PMID- 15561612
TI  - Absolute line intensity measurements of hot bands for carbonyl sulfide at 12
      microm.
AB  - Using diode-laser spectroscopy, the intensities of 58 lines of the v(1) + v(1/2) 
      v(1/2) band and 36 lines of the 2v(1) - v(1) band of OCS have been measured. The
      corresponding band strengths S(0)(v) and the vibrational transition dipoles
      micro(v) have been derived through least squares fitting of these individual
      intensities. The band strengths values have been determined with a precision
      better than 2.5%.

PMID- 15561613
TI  - Real-time monitoring of Yb vapor density using an extended cavity violet diode
      laser.
AB  - Based on laser absorption spectroscopy (LAS), we developed a vapor density
      monitor for controlling the vaporization rate of Yb using a tunable diode laser.
      The laser source consisted of an extended cavity violet diode laser which has an
      emission wavelength of 398.8 nm coincident with the Yb absorption transition
      line, 6s(2) 1S(0)-6s6p 1P(1). The light emitted from the diode laser was
      transmitted across an atomic vapor column generated by heating the Yb metal,
      while the laser frequency was scanned across the atomic transition line. By
      comparing the amount of incident light to the amount of light transmitted after
      the light passed through the vapor column, the vapor density was determined using
      the Beer's law. From the experimental results, we demonstrated that the diode
      laser-based LAS operated successfully for the real-time monitoring of the Yb
      vapor density.

PMID- 15561614
TI  - Infrared diode laser absorption spectroscopy of C(2)H(2) and C(2)H(6) in
      capacitively coupled methane RF discharges.
AB  - Low-temperature RF discharges with methane as feed gas are widely used for the
      deposition of hydrogenated films. The film properties depend strongly on the
      chemical composition and therefore two of the main stable products in this kind
      of discharge, namely ethane (C(2)H(6)) and acetylene (C(2)H(2)), have been
      measured for the understanding of the reaction kinetics in the plasma. An
      absorption spectrometer has been built up for the investigation of the
      concentrations of these as a function of the input power and the flow rate. The
      time scales for reaching steady state after the discharge is switched on and the
      depletion time scale after the plasma is switched off have been determined.
      Assuming the recombination of CH(3) molecules to be the only production mechanism
      for C(2)H(6) and using a simplified rate equation, the measured densities of
      C(2)H(6) can be reproduced very well by analytical fitting curves.

PMID- 15561615
TI  - Line frequency shift measurements by diode-laser spectroscopy for CH(3)D-Xe.
AB  - The pressure-induced Xe shifting and broadening coefficients for five lines of
      12CH(3)D in the nu(3) band near 7.5 microm have been measured using a tunable
      diode-laser spectrometer. The frequency shift was determined from the
      simultaneous record of the Xe-broadened line and the same line of pure CH(3)D at
      low pressure. Comparisons are made with the results of theoretical calculations
      based on a semiclassical model involving the atom-atom Lennard-Jones (LJ)
      potential.

PMID- 15561616
TI  - High precision measurements of atmospheric nitrous oxide and methane using
      thermoelectrically cooled mid-infrared quantum cascade lasers and detectors.
AB  - A compact, fast response, mid-infrared absorption spectrometer using
      thermoelectrically (TE) cooled pulsed quantum cascade (QC) lasers and TE
      detectors has been developed to demonstrate the applicability of QC lasers for
      high precision measurements of nitrous oxide and methane in the earth's
      atmosphere. Reduced pressure extractive sampling with a 56 m path length, 0.5 l
      volume, multiple pass absorption cell allows a time response of <0.1s which is
      suitable for eddy correlation flux measurements for these gases. Precision of 0.3
      ppb (rms, 1s averaging time) or 0.1% of the ambient concentration for N(2)O (4
      ppb or 0.2% of ambient for CH(4)), has been demonstrated using QC lasers at 4.5
      microm (7.9 microm for CH(4)), corresponding to an absorbance precision of 4 x
      10(-5) Hz(-1/2) (8 x 10(-5) Hz(-1/2) for CH(4)). Stabilization of the temperature
      of the optical bench and the pulse electronics results in a minimum Allan
      variance corresponding to 0.06 ppb for N(2)O with an averaging time of 100 s (0.7
      ppb with an averaging time of 200 s for CH(4)). The instrument is capable of long
      term, unattended, continuous operation without cryogenic cooling of either laser
      or detector.

PMID- 15561617
TI  - Tunable single-frequency diode laser at wavelength lambda = 1.645 microm for
      methane concentration measurements.
AB  - This paper deals with the development of a novel single-frequency tunable diode
      laser with fiber-optic output for gas-analysis applications. The approach we
      propose is a convenient, simple and cheap solution for spectroscopy of single
      absorption lines of any gases having absorption bands in the optical fiber
      transparency window (0.7 microm/1.7 microm). The presence of fiber-optic output
      is an additional advantage for remote sensing applications. The laser operation
      is demonstrated as applied to R7 line of 2 nu(3) methane absorption band at
      lambda = 1.645 microm. The mode-hop-free tuning range of 35 GHz (1.2 cm(-1)) has
      been achieved.

PMID- 15561618
TI  - Tunable optically pumped lead-chalcogenide mid-infrared emitters on Si
      substrates.
AB  - Two types of novel lead-chalcogenide mid-IR emitters grown by molecular beam
      epitaxy (MBE) on Si or BaF(2) substrates are described:PbSe/PbEuSe edge emitting
      double heterostructure (DH) and quantum well (QW) lasers are pumped optically
      with low-cost III-V laser-diodes. They emit in the 3-6 microm range with powers
      up to 200 mW. Tuning is performed by temperature change and/or mechanically if
      bars with slightly tapered composition are used. A "wavelength transformer", a
      PbSe/PbEuSe active resonant cavity with top and bottom Bragg mirror transforms
      the incoming 0.8 microm pump radiation to e.g. 4.2 microm wavelength. It operates
      at room temperature, width and value of the emission line is determined by
      design.

PMID- 15561619
TI  - Concentration measurements of ozone in the 1200-300ppbv range: an intercomparison
      between the BNM ultraviolet standard and infrared methods.
AB  - Simultaneous ultraviolet (UV) and infrared (IR) measurements of ozone
      concentration in air in the 1200-300 ppbv range have been performed using the
      ultraviolet absorption in the Hartley band at 0.2537 microm and the infrared
      absorption of a doublet at 9.507 microm in the nu(3) vibration-rotation band.
      Infrared concentration measurements were achieved using the tunable diode laser
      spectrometer of LPMA in Paris with interferometric control of the emitted
      wavelength while the UV concentration measurements were performed with the 49PS
      Megatec ozone generator of the Bureau National de Metrologie (BNM). The
      simultaneous recording of spectra of a reference cell filled with pure distilled
      ozone and of a low concentration mixture inside a long absorbing path Herriott
      cell allows to carry out infrared concentration measurements with an accuracy of
      the same order as the ultraviolet ones and provides the instrumental parameters
      of the spectrometer corresponding to each concentration measurement, which
      reduces systematic errors. Within the respective absolute uncertainties proper to
      the two techniques, no systematic discrepancy was evidenced between the IR and
      the UV measurements. The ozone ultraviolet absorption coefficient value
      determined by Hearn (308.3 +/- 4 cm(-1)atm(-1)) and used by the BNM and the
      National Institute of Standards and Technology (NIST) is confirmed by the present
      work.

PMID- 15561620
TI  - Near-infrared tunable diode laser spectrometer for the remote sensing of vehicle
      emissions.
AB  - A near-infrared diode laser-based spectrometer has been designed and built for
      the remote sensing of vehicle emissions. It detects carbon monoxide and carbon
      dioxide absorptions around 1580 nm and can provide the ratio CO/CO(2) for vehicle
      exhaust studies. The system is battery powered and is designed to sit
      unobtrusively at the side of the road. The optics and electronics of the system
      is described and preliminary results are presented from field trials. Extensions
      to the spectrometer in terms of sensitivity by detection of the more intense
      first overtone of carbon monoxide around 2320 nm are described, in addition to
      further work on other species of interest.

PMID- 15561621
TI  - Plasma-chemical CO(2) decomposition in a non-self-sustained discharge with a
      controlled electronic component of plasma.
AB  - Carbon dioxide decomposition in a non-self-sustained discharge was studied by the
      methods of diode laser spectroscopy and mass-spectrometry. It was shown that the
      effective control of the mechanism of a plasmachemical reaction is possible by
      varying the parameter E/N. This allowed us to reduce the energy cost of
      dissociation CO(2) by more than on an order of magnitude as compared to the
      dissociation process in a self-sustained glow discharge.

PMID- 15561622
TI  - In situ sensing of the middle atmosphere with balloonborne near-infrared laser
      diodes.
AB  - Since 1997, two near-infrared laser diode sensors have been developed with the
      support of the CNES, the French space agency, to provide in situ data of H(2)O,
      CH(4) and CO(2) in the middle atmosphere. The realized instruments were flown
      from stratospheric balloons within the framework of European campaigns for the
      study of stratospheric ozone and water vapor and were involved in the validation
      of the ODIN and ENVISAT satellites. In this paper, we describe the developed
      laser probing technique, we report atmospheric measurements and finally we
      discuss future perspectives, particularly the in situ laser sensing of the lower
      atmosphere of Mars and the implication of the laser hygrometers in balloon
      campaigns at mid-latitudes and tropical regions to investigate the sources and
      sinks of stratospheric H(2)O.

PMID- 15561623
TI  - Diode laser spectroscopy of ammonia and ethylene overtones.
AB  - Some overtone absorption lines of ammonia and ethylene have been examined by
      using a tunable diode laser (TDL) spectrometer in the region around 12,650 and
      11,800 cm(-1), respectively. The spectrometer sources are commercially available
      double heterostructure InGaAlAs and AlGaAs TDLs operating in the "free-running"
      mode. The high resolving power ( approximately 10(7) ) of the spectrometer
      permitted the detection and the study of the line positions of such molecules
      with a precision better than 0.01 cm(-1). In order to maximize the signal to
      noise ratio and to extract the necessary informations either on the line width
      and on the line position for the detected molecular resonances, the wavelength
      modulation spectroscopy (WMS) along with the second harmonic detection techniques
      have been applied. For this purpose, the fitting procedure took into account the
      instrumental effects and the amplitude modulation (AM) always associated with the
      frequency modulation (FM) of these type of sources. This technique permitted also
      the measurement of the collisional-broadening and -shifting coefficients by
      different buffer gases at room temperature.

PMID- 15561624
TI  - X-ray studies and time-resolved photoluminescence on optically pumped antimonide
      based midinfrared type-II lasers.
AB  - We report on high-resolution X-ray diffraction and time-resolved
      photoluminescence (TR-PL) studies of antimonide-based midinfrared (MIR) type-II
      laser samples. A structural characterization taking into account asymmetrical
      strain, layer tilting, and relaxation enables an accurate determination of the
      average lattice constant of the active region and the composition of the cladding
      layers. By designing the antimonide-to-arsenide interfaces, we achieve exact
      lattice matching of the active region to the substrate. Non-radiative
      recombination processes are investigated with time-resolved photoluminescence.
      The samples are also characterized under optically pumped laser operation. By an
      examination of the time-integrated and time-resolved amplified spontaneous
      emission (TR-ASE), we investigate the modal gain and gain dynamics. The variable
      stripe length method is combined with the TR-PL approach. Compared to the time
      integrated gain spectra the spectral dependence of the maximum and minimum time
      resolved gain shows a broad plateau. The full width half maximum (FWHM) of the TR
      ASE pulse is 5.5 +/- 0.5 ps. Thus, short pulses in this range should be
      achievable upon laser operation. The active regions of the laser structures
      investigated here are promising subunits of type-II quantum cascade lasers.

PMID- 15561625
TI  - Element selective detection of molecular species applying chromatographic
      techniques and diode laser atomic absorption spectrometry.
AB  - Tunable diode laser atomic absorption spectroscopy (DLAAS) combined with
      separation techniques and atomization in plasmas and flames is presented as a
      powerful method for analysis of molecular species. The analytical figures of
      merit of the technique are demonstrated by the measurement of Cr(VI) and Mn
      compounds, as well as molecular species including halogen atoms, hydrogen, carbon
      and sulfur.

PMID- 15561626
TI  - Diode laser spectroscopy of the nu(8) band of the SF(5)Cl molecule.
AB  - Diode laser spectra of SF(5)Cl have been recorded in the nu(8) band region at a
      temperature of ca. 240 K, a pressure of 0.25 mbar and an instrumental bandwidth
      of ca. 0.001 cm(-1). Four regions have been studied: a first one in the P-branch
      (906.849-907.687 cm(-1)), a second one in the Q-branch (910.407-910.944 cm(-1)),
      and two other ones in the R-branch (913.957-914.556 and 917.853-918.705 cm(-1) ).
      The whole nu(1)/nu(8) dyad of SF(5)35Cl has been previously recorded in the group
      of Professor H. Burger in Wuppertal, thanks to a Fourier transform infrared
      spectrometer. These data have thus been combined with our diode laser ones in the
      aim of refining the analysis. We used an effective Hamiltonian developed up to
      the fourth order and a set of programs called C(4nu)TDS. One thousand three
      hundred and forty-six transitions for nu(1), 495 (FTIR: 351; diode laser: 144)
      transitions for nu(8), and 406 ground state combination differences have been
      assigned and fitted. A global fit has been obtained with a rms of 0.00081 cm(-1)
      for the nu(1) band, 0.0012 cm(-1) for the FTIR data of the nu(8) band, 0.00055
      cm(-1) for the diode laser data of this same band, and 0.00064 cm(-1) for the
      ground state. It appears that more data (for instance, using a supersonic jet)
      are still necessary to obtain a completely satisfactory analysis of the nu(8)
      region.

PMID- 15561627
TI  - Diode laser wavelength modulated spectroscopy of I(2) at 675 nm.
AB  - A free-running diode laser has been used to examine the spectrum of 127I(2) near
      675 nm using wavelength modulation spectroscopy. Twelve transitions have been
      observed in the region between 14818.0 and 14819.3 cm(-1), all of which are
      accounted for by previously published constants. Changes in quadrupole coupling
      constants, DeltaeQq, have been determined for all lines. Pressure broadening and
      shift coefficients have been determined for two unblended lines for broadening by
      air, argon, and water vapor.

PMID- 15561628
TI  - Determination of molecular parameters for 1,3-butadiene and propylene using
      infrared tunable diode laser absorption spectroscopy.
AB  - A technique has been developed for the determination of molecular parameters,
      including infrared absorption line positions, strengths, and nitrogen-broadened
      half-widths for 1,3-butadiene (C(4)H(6)) and propylene (C(3)H(6)). The parameters
      for these two molecules are required for quantitation using Tunable Diode Laser
      Absorption Spectroscopy (TDLAS). These molecules have populations of highly
      overlapping infrared absorption lines in their room temperature spectra. The
      technique reported here provides a procedure for estimating the molecular
      parameters for these overlapping absorption lines from quantitative reference
      spectra taken with the TDLAS instrument at different pressures and
      concentrations. The system was developed for the quantitation of gaseous
      constituents in a single puff of cigarette smoke and this paper will describe the
      procedure and some of the factors that influence the accuracy of quantitation for
      1,3-butadiene, including the approach taken to minimize the adverse effects of
      the absorption due to propylene in the same spectral region.

PMID- 15561629
TI  - Application of antimonide diode lasers in photoacoustic spectroscopy.
AB  - First investigations of photoacoustic (PA) spectroscopy (PAS) of methane using an
      antimonide semiconductor laser are reported. The laser fabrication is made in two
      steps. The structure is firstly grown by molecular beam epitaxy, then a metallic
      distributed-feedback (DFB) grating is processed. The laser operates at 2371.6 nm
      in continuous wave and at room temperature. It demonstrates single-mode emission
      with typical tuning coefficients of 0.04 nm mA(-1) and 0.2 nm K(-1). PA detection
      of methane was performed by coupling this laser into a radial PA cell. A
      detection limit of 20 ppm has been achieved in a preliminary configuration that
      was not optimised for the laser characteristics.

PMID- 15561630
TI  - Quad quantum cascade laser spectrometer with dual gas cells for the simultaneous
      analysis of mainstream and sidestream cigarette smoke.
AB  - A compact, fast response, infrared spectrometer using four pulsed quantum cascade
      (QC) lasers has been applied to the analysis of gases in mainstream (MS) and
      sidestream (SS) cigarette smoke. QC lasers have many advantages over the
      traditional lead-salt tunable diode lasers, including near room temperature
      operation with thermoelectric cooling and single mode operation with improved
      long-term stability. The new instrument uses two 36 m, 0.3 l multiple pass
      absorption gas cells to obtain a time response of 0.1s for the MS smoke system
      and 0.4s for the SS smoke system. The concentrations of ammonia, ethylene, nitric
      oxide, and carbon dioxide for three different reference cigarettes were measured
      simultaneously in MS and SS smoke. A data rate of 20Hz provides sufficient
      resolution to determine the concentration profiles during each 2s puff in the MS
      smoke. Concentration profiles before, during and after the puffs also have been
      observed for these smoke constituents in SS smoke. Also, simultaneous
      measurements of CO(2) from a non-dispersive infrared (NDIR) analyzer are obtained
      for both MS and SS smoke. In addition, during this work, nitrous oxide was
      detected in both the MS and SS smoke for all reference cigarettes studied.

PMID- 15561631
TI  - Multi-gas sensing based on photoacoustic spectroscopy using tunable laser diodes.
AB  - Multi-hydrogenated compounds detection based on photoacoustic (PA) spectroscopy
      is reported. Three near-infrared semiconductor lasers are used with a resonant PA
      cell operated in its first longitudinal mode to monitor methane, water vapour and
      hydrogen chloride in the parts per million range. The design of our cell results
      from simulations performed in order to optimise its performances. Influence of
      the buffer gas on the PA signal has also been analysed, both theoretically and
      experimentally. A reduction of the PA signal of almost one order of magnitude has
      been observed between N(2) and He, which demonstrates the importance of the
      buffer gas in PA spectroscopy. Finally, detection limits of 0.5 ppm of CH(4) and
      3 ppm of HCl has been achieved experimentally in nitrogen and an H(2)O
      sensitivity of 0.2 ppm has been estimated.

PMID- 15561632
TI  - Stabilization, injection and control of quantum cascade lasers, and their
      application to chemical sensing in the infrared.
AB  - Quantum cascade lasers (QCLs) are a relatively new type of semiconductor laser
      operating in the mid- to long-wave infrared. These monopolar multilayered quantum
      well structures can be fabricated to operate anywhere between 3.5 and 20 microm,
      which includes the molecular fingerprint region of the infrared. This makes them
      an ideal choice for infrared chemical sensing, a topic of great interest at
      present. Frequency stabilization and injection locking increase the utility of
      QCLs. We present results of locking QCLs to optical cavities, achieving relative
      linewidths down to 5.6 Hz. We report injection locking of one distributed
      feedback grating QCL with light from a similar QCL, demonstrating capture ranges
      of up to +/-500 MHz, and suppression of amplitude modulation by up to 49 dB. We
      also present various cavity-enhanced chemical sensors employing the frequency
      stabilization techniques developed, including the resonant sideband technique
      known as NICE-OHMS. Sensitivities of 9.7 x 10(-11) cm(-1) Hz(-1/2) have been
      achieved in pure nitrous oxide.

PMID- 15561633
TI  - Photo-acoustic measurements of gas and aerosol absorption with diode lasers.
AB  - The results of designing multipurpose high-sensitive photo-acoustic (PA)
      detectors and their application to high-resolution diode laser spectroscopy of
      molecular gases, gas analysis, and aerosol absorption measurements are summarized
      in this paper. The hardware and software of the diode laser spectrometer with a
      Helmholtz resonant PA detector providing an absorption sensitivity limit of
      better than 10(-7)Wm(-1)Hz(-1/2) are described. A procedure is proposed for an
      experiment involving the measurements of the rotational structure of hot
      vibrational bands of molecules. The results of the application of the nonresonant
      PA cell with temporal resolution of signals to measurements of weak nonresonant
      absorption of gases and soot aerosols are presented, and the possibility of
      creating a broad-band PA laser diode aerosol-meter is discussed.

PMID- 15561634
TI  - Development of a stabilized low temperature infrared absorption cell for use in
      low temperature and collisional cooling experiments.
AB  - We have constructed a stabilized low temperature infrared absorption cell cooled
      by an open cycle refrigerator, which can run with liquid nitrogen from 250 to 80K
      or with liquid helium from 80K to a few kelvin. Several CO infrared spectra were
      recorded at low temperature using a tunable diode laser spectrometer. These
      spectra were analyzed taking into account the detailed effects of collisions on
      the line profile when the pressure increases. We also recorded spectra at very
      low pressure to accurately model the diode laser emission. Spectra of the R(2)
      line in the fundamental band of 13CO cooled by collisions with helium buffer gas
      at 10.5K and at pressures near 1 Torr have been recorded. The He-pressure
      broadening parameter (gamma(0) = 0.3 cm(-1) atm(-1)) has been derived from the
      simultaneous analysis of four spectra at different pressures.

PMID- 15561636
TI  - The role of exercise for weight loss and maintenance.
AB  - Exercise provides a means of increasing energy expenditure and may help adjust
      energy balance for weight loss and maintenance. At least 30 minutes a day of
      moderate intensity aerobic exercise per day is recommended for weight loss and
      maintenance but greater amounts appear to increase the magnitude of weight loss
      and maintenance. Resistance training has recently been shown to have positive
      effects on body composition but does not typically show significant decreases in
      weight. Regardless of weight loss, both aerobic exercise and resistance training
      have been shown to diminish risk factors for cardiovascular disease and diabetes.
      Since exercise is only effective if sustained, behavioural strategies such as
      self-monitoring, goal setting, social support, etc. are used to help individuals
      start and maintain exercise programs and show improved results compared to
      exercise programs without behavioural strategies. The available evidence
      indicates that exercise is an important component of weight loss and perhaps the
      best predictor of weight maintenance.

PMID- 15561637
TI  - Is there an optimal macronutrient mix for weight loss and weight maintenance?
AB  - Low carbohydrate diets are gaining popularity, however there is no clear
      consensus regarding their safety and efficacy for weight loss. Proponents of
      these diet plans advocate dramatic reductions in carbohydrate intake to combat
      insulin resistance and hyperinsulinaemia, which they claim are responsible for
      obesity. There are no long-term studies that directly compare the weight loss
      potential of low versus higher carbohydrate diets. Evidence from randomized
      controlled trials suggests that low carbohydrate diets may enable short-term
      weight loss by facilitating reduced energy intakes, however poor dietary
      compliance may prevent long-term success. Unbalanced nutrient profiles may
      increase the risk of adverse health consequences in adherents. Low carbohydrate
      diets should not be recommended at this time due to a lack of adequate long-term
      follow up data. Successful weight loss occurs through the creation of a sustained
      energy deficit, and should be achieved through a combination of exercise and a
      nutritionally balanced and varied diet.

PMID- 15561638
TI  - Modern, new pharmacotherapy for obesity. A gastrointestinal approach.

PMID- 15561639
TI  - Psychological aspects of eating disorders.
AB  - Eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder)
      are regarded as psychiatric syndromes that have some relationship to obesity.
      This review describes current clinical and scientific knowledge concerning the
      clinical descriptions of these disorders, etiology of each disorder, diagnostic
      signs, and treatment approaches that have been found to be efficacious. Anorexia
      nervosa is a very serious eating disorder that is associated with severe medical
      complications. Anorexia nervosa is very difficult to successfully treat, even
      when intensive inpatient methods are used. Bulimia nervosa and binge eating
      disorder are typically less severe eating disorders and are more easily treated
      using outpatient therapy. Pharmacotherapy has not been found to be an effective
      treatment for anorexia nervosa, but it has been used successfully with bulimia
      nervosa and binge eating disorder. Psychotherapy approaches have been
      successfully employed for all three eating disorders. The review concludes with
      an integrative perspective that illustrates the similarities and differences of
      the eating disorders and obesity.

PMID- 15561640
TI  - Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH):
      diagnosis and clinical course.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing
      fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion
      arises because of abnormal aminotransferases or a bright liver on abdominal
      ultrasound. It should be suspected during evaluation of associated conditions as
      obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other
      potential causes of liver disease and may include a liver biopsy, the only method
      able to confirm features of necroinflammation and fibrosis that define NASH and
      its prognostic implications. Indeed, the presence of necroinflammation has been
      associated with a significant risk of progression to cirrhosis and eventually
      hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been
      associated with an increased risk of liver fibrosis and progression to cirrhosis.
      Given the high prevalence of NAFLD, general measures of life-style changes,
      focusing on exercise, diet, and total alcohol abstinence, should be implemented
      before a liver biopsy is considered.

PMID- 15561641
TI  - Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH):
      treatment.
AB  - Non-alcoholic fatty liver disease is now recognized as a cause of potentially
      progressive liver damage, posing patients at risk of advanced liver failure.
      Unfortunately, the natural history of disease is only partly known, the disease
      is slowly progressive and therapeutic outcomes are difficult to define. These
      factors have limited therapeutic trials to pilot studies, and very few randomized
      controlled studies are available. The concept that insulin-resistance, coupled
      with oxidative stress, may be the underlying mechanism responsible for fat
      accumulation and disease progression points to insulin-sensitizing agents
      (metformin, thiazolidinediones) as the most promising drugs. They proved
      effective in reducing enzyme levels in the short period, but very limited
      information is available on liver histology, not to say progression to liver cell
      failure. Large, long-term, placebo-controlled randomized studies are eagerly
      awaited. Outside controlled studies, nutritional counselling and physical
      exercise aimed at moderate weight loss remain the basis of any therapeutic
      intervention.

PMID- 15561642
TI  - The relation between body mass and gastro-oesophageal reflux.
AB  - Obesity has, among physicians, since long been considered to cause gastro
      oesophageal reflux. The evidence in support of this belief has been scarce,
      however. During the last few years some population-based studies have addressed
      this clinically important issue. These studies demonstrated a clear and dose
      dependent association between increasing degrees of overweight and gastro
      oesophageal reflux. The mechanisms by which obesity causes reflux are unknown,
      although there is some limited data suggesting that hiatal hernia may be the
      causal link between obesity and reflux. Moreover, some evidence has been
      presented showing that obesity is clearly a stronger risk factor among women than
      among men, and that the relation between overweight and reflux is substantially
      augmented by postmenopausal hormone therapy. The data so far available point in
      the direction of oestrogens, the activity of which is strengthened by increasing
      body mass, being responsible for this effect. If the results are repeated in
      future studies, postmenopausal therapy might be avoided among obese females
      suffering from severe reflux. Weight-reduction seems to reduce the risk of
      symptomatic gastro-oesophageal reflux disease, indicating that such strategy
      might be a useful tool in the treatment of reflux.

PMID- 15561643
TI  - Obesity: epidemiology and clinical aspects.
AB  - At the beginning of the 21st Century, obesity has become the leading metabolic
      disease in the World. So much so, that the World Health Organisation refers to
      obesity as the global epidemic. In fact, obesity is a common disease affecting
      not only affluent societies but also developing countries. Currently 300 million
      people can be considered as obese and, due to the rising trend in obesity
      prevalence, this figure could double by year 2025 if no action is taken against
      this threat. In terms of health impairment, the importance of obesity lies in the
      fact that, besides being a disease in itself, it is a risk for many other
      diseases, mainly from the metabolic and cardiovascular area. Among these, type 2
      diabetes, dyslipemia, hyperuricemia, arterial hypertension and cardiovascular
      disease are the most frequent. Also, respiratory diseases such as obesity
      hypoventilation syndrome and obstructive sleep apnoea syndrome are strongly
      associated with obesity.

PMID- 15561644
TI  - Obesity: surgical options.
AB  - Conservative treatment has been shown in long-term studies to be ineffective in
      morbid obesity. Surgical treatments break down into restrictive, malabsorptive,
      combined restrictive and malabsorptive or motility-reducing procedures.
      Laparascopic implantation of an adjustable gastric band is an efficient
      restrictive measure for treating the majority of patients with this condition.
      The adjustable gastric band enables weight loss and food intake to be adapted to
      the individual patient's need. Eighty percent to 90% of these patients can expect
      to lose 55-70% of their excess weight. Vertical banded gastroplasty is losing
      ground among the restrictive options. Preliminary experiences are encouraging but
      the long term results are disappointing when assessed by the standard criteria.
      Gastric bypass is gaining ground in Europe and a standard procedure in USA. This
      operation is estimated to give 70-80% excess weight loss and provide better
      quality of life than restrictive procedures. The biliopancreatic diversion with
      duodenal switch combines a sleeve gastrectomy with a duodenoileal switch to
      achieve maximum weight loss. Consistent excess weight loss between 70 and 80% is
      achieved with acceptable decreased long-term nutritional complications. The
      laparoscopic approach to this procedure has successfully created a surgical
      technique with optimum benefit and minimal morbidity, especially in the super
      obese patient. Intra-gastric stimulation is the least invasive surgical procedure
      at present. However, the excess weight loss is lowest with this method at only
      32% in the first 2 years after the operation. Provided safety recommendations are
      observed, laparoscopic operations for obesity are fairly low-risk. The mortality
      rate in centres with experienced staff is less than 0.3%. Surgical treatment for
      obesity has proved that it is the best and most effective means of preventing the
      life-threatening complications and serious degenerative problems associated with
      morbid obesity. There is no one operation that is effective for all patients.

PMID- 15561645
TI  - Risk of gastrointestinal malignancies and mechanisms of cancer development with
      obesity and its treatment.
AB  - Gastrointestinal malignancies may be associated with obesity, defined
      specifically by increased body-mass index, and based largely on environmental
      factors rather than genetics. In particular, there seems to be a definite
      increase in the incidence of both oesophageal and colorectal cancer. Mechanisms
      associated with obesity include a particular metabolic state characterized by
      hyperinsulinemia, or insulin resistance, along with elevated serum leptin. Leptin
      is derived from adipocytes and appears to play a role in the regulation of
      ghrelin, a peptide derived from the stomach and small intestine that stimulates
      appetite and weight gain. In addition to these metabolic changes, there are other
      anatomical alterations that may indirectly predispose to cancer, including the
      predisposition of obesity to gastroesophageal reflux and, possibly, oesophageal
      cancer. Other mechanisms may involve adipocyte-derived cytokines, or adipokines,
      that may serve as signalling devices in the pathogenesis of cancer. Finally,
      pharmacologic and surgical avenues available for treatment of obesity, including
      lipase inhibitors and gastric or jejuno-ileal bypass procedures may set the stage
      for subsequent gastric or intestinal tract cancer.

PMID- 15561647
TI  - Gabapentin: a pooled analysis of adverse events from three clinical trials in
      patients with postherpetic neuralgia.
AB  - BACKGROUND: Gabapentin has been shown to be well tolerated and effective in the
      management of the pain associated with postherpetic neuralgia (PHN). It is
      assumed that adverse events occurring with gabapentin are dose related, their
      frequency and severity increasing with increasing doses. OBJECTIVE: The aim of
      this study was to assess the dose dependence of adverse events with gabapentin by
      determining the relationship between increasing doses of gabapentin and the onset
      and/or worsening of adverse events in patients with PHN. METHODS: Data were
      pooled from 3 randomized, double-blind, placebo-controlled, parallel-group
      studies of gabapentin that focused on or included patients with PHN. Gabapentin
      was initiated at 300 mg/d and titrated to maintenance doses of 1800 to 3600 mg/d
      by day 12 to 24. The analysis of adverse events was based on 3 distinct groups:
      patients who received gabapentin <1800 mg/d, those who received gabapentin
      >or=1800 mg/d, and those who received placebo. Patients who were given higher
      doses of gabapentin had already received lower doses. An adverse event was
      recorded at the dose of its first onset and recorded again if its severity
      worsened at a higher dose. RESULTS: This study included data from 603 patients
      with PHN: 358 patients (196 [54.7%] women, 162 [45.3%] men; mean [SD] age, 72.3
      [10.3] years) received gabapentin, and 245 (133 [54.3%] women, 112 [45.7%] men;
      mean [SD] age, 73.3 [10.7] years) received placebo. The 3 most common adverse
      events were dizziness, somnolence, and peripheral edema. Patients receiving
      gabapentin >or=1800 mg/d had a higher incidence of peripheral edema (7.5%) than
      those receiving gabapentin <1800 mg/d (1.4%) or placebo (1.6%) (P<0.002,
      gabapentin >or=1800 mg/d vs placebo). In contrast, the incidence of dizziness and
      somnolence was not higher in patients receiving gabapentin >or=1800 mg/d compared
      with those in the other groups. Compared with placebo recipients, patients
      receiving gabapentin <1800 mg/d reported a significantly greater frequency of
      dizziness (20.2% gabapentin <1800 mg/d vs 7.4% placebo; P<0.002) and somnolence
      (14.9% vs 5.8%, respectively; P=0.005). However, at >or=1800 mg/d, rates of
      dizziness (9.7%) and somnolence (6.9%) were comparable to those with placebo.
      Discontinuation rates were comparable between patients receiving gabapentin and
      those receiving placebo. CONCLUSIONS: In this pooled analysis of adverse-event
      data from 3 clinical trials in patients with PHN, the incidence of peripheral
      edema was increased when gabapentin was titrated to >or=1800 mg/d. Dizziness and
      somnolence, the other most commonly occurring adverse events, were transient and
      did not occur more frequently or worsen with titration to >or=1800 mg/d. Based on
      these findings, it does not appear that safety concerns should limit titration of
      gabapentin to achieve optimal efficacy.

PMID- 15561648
TI  - Use of potentially inappropriate pain-related medications in older adults with
      painful neuropathic disorders.
AB  - BACKGROUND: Although older adults with painful neuropathic disorders (PNDs) would
      appear to be at elevated risk for receiving potentially inappropriate pain
      related medications, the extent of such drug use in this population is unknown.
      OBJECTIVE: The goal of this study was to assess the use of potentially
      inappropriate pain-related medications among patients with PNDs aged >or=65
      years. METHODS: Using a large, integrated US health insurance database, we
      identified all persons aged >or=65 years with >or=2 medical encounters involving
      diagnoses of PNDs during calendar year 2000. Patients with <30 days of continuous
      eligibility for health benefits during the study year were excluded from the
      sample. Use of potentially inappropriate pain-related medications (as defined by
      the 1997 Beers criteria) was then examined based on information contained in paid
      pharmacy claims for all remaining patients. RESULTS: We identified 22,668
      patients with PNDs aged >or=65 years (mean [SD] age, 73.9 [6.0] years; 58.6%
      female). Almost one half (11,233 [49.6%]) of patients received >or=1 potentially
      inappropriate pain-related medication, including propoxyphene (26.7%) and
      amitriptyline (10.2%). Women were more likely than men to receive these
      medications (54.2% vs 43.0%, respectively; P<0.01), and use increased with age
      (47.6%, 51.8%, and 52.8% in those aged 65-74 years, 75-84 years, and >or=85
      years, respectively; overall comparison, P<0.01). Among patients with only 1 PND,
      the use of potentially inappropriate medications was highest among those with
      postherpetic neuralgia (70.1%). CONCLUSIONS: Use of potentially inappropriate
      pain-related medications among older adults with PNDs is common. Further research
      is needed to ascertain whether the benefits of these agents outweigh their risks
      in this population.

PMID- 15561649
TI  - Use of gastrointestinal preventive therapy among elderly persons receiving
      antiarthritic agents in Nova Scotia, Canada.
AB  - BACKGROUND: Two different strategies, referred to as gastrointestinal (GI)
      preventive therapy (GIPT), have been recommended for high-risk patients to
      prevent GI complications associated with antiarthritic therapy with nonsteroidal
      anti-inflammatory drugs (NSAIDs): (1) use of a gastroprotective agent (GPA) along
      with the NSAID or (2) use of a cyclooxygenase-2-selective inhibitor (COX-2SI).
      The COX-2SIs rofecoxib and celecoxib have been shown to be as effective as
      traditional NSAADs for pain relief, but with an improved GI safety profile.
      OBJECTIVE: The purpose of this study was to examine the utilization of GIPT by
      elderly persons in Nova Scotia who were taking antiarthritic medications and to
      identify the factors associated with their use of GIPT. METHODS: A retrospective,
      cross-sectional study was conducted using administrative data from the Nova
      Scotia Seniors' Pharmacare Program database. Study participants were aged >or=65
      years and had filled a prescription for a COX-2SI, a traditional NSAID, or high
      dose aspirin at some point between January 1, 2001 and August 31, 2002. Subjects
      with at least 1 risk factor (as defined by our study) who received GIPT were
      classified as receiving appropriate therapy. Subjects with risk factors who did
      not receive GIPT were classified as potential underutilizers of GIPT. Subjects
      without risk factors who received GIPT were classified as potential overutilizers
      of GIPT. Descriptive statistics were presented, and factors independently
      associated with receiving GIPT were assessed using logistic regression. RESULTS:
      The study included 14,587 seniors: 3647 used COX-2SIs, 9412 used traditional
      NSAIDs alone, and 1528 used traditional NSAADs plus a GPA. Subjects were
      predominantly female (age range, 65-74 years). In subjects with at least 1 risk
      factor, 63% were classified as potential underutilizers of GIPT. Thirty-three
      percent of subjects with no risk factors were classified as potential
      overutilizers of GIPT. Factors significantly associated with receiving a GIPT
      included Female gender, annual income >$50,000, urban residence, age >or=75
      years, GI complication in the previous year, and concomitant use of warfarin or
      corticosteroids. CONCLUSION: Potential under utilization of GIPT in this subject
      population was more prevalent than potential overutilization of GIPT. Although
      all hypothesized risk factors were significantly associated with receiving GIPT,
      physician education on GI risk factors might improve prescribing of GIPT for
      elderly persons in Nova Scotia.

PMID- 15561650
TI  - Clinical efficacy, tolerability, and cost savings associated with the use of open
      label metronidazole plus ceftriaxone once daily compared with
      ticarcillin/clavulanate every 6 hours as empiric treatment for diabetic lower
      extremity infections in older males.
AB  - BACKGROUND: Patients with diabetes mellitus, particularly those with poor glucose
      control, commonly experience various medical complications related to the disease
      (eg, renal impairment, decreased peripheral vascular circulation, suppressed
      immune function). Infections of the lower extremities can range from superficial
      cellulitis to ulcerative, deep soft-tissue infections to osteomyelitis that
      necessitates some degree of amputation. OBJECTIVE: This study compared the
      efficacy, tolerability, and cost differences associated with the use of
      metronidazole plus ceftriaxone (MTZ/CTX) given once daily with those of
      ticarcillin/clavulanate potassium (T/C) given every 6 hours in hospitalized older
      males with diabetic lower-extremity infections. METHODS: This prospective, open
      label study was conducted at a Veterans Affairs Medical Center. Male patients
      with diabetes and a lower-extremity infection were randomized to receive MTZ/CTX
      1 g once daily or T/C 3.1 g every 6 hours. Treatment success was determined at 96
      hours or on discontinuation of antibiotic. Success was measured in terms of body
      temperature <38.3 degrees C (100.6 degrees F), normalization of the finger-stick
      blood sugar concentration, improvement in wound staging, or a white blood cell
      count <10,000 cells/mm3. Medication acquisition costs per treatment arm were
      calculated and compared. RESULTS: Seventy patients were enrolled in the study (36
      MTZ/CTX, 34 T/C). The study population had a mean (SD) age of 63.8 (10.8) years,
      a duration of diabetes of 12.4 (9.1) years, 0.5 (0.7) diabetes-related
      comorbidities, and an initial creatinine clearance of 67.1 (26.0) mL/min. There
      were no significant differences between groups at randomization. At 96 hours,
      treatment success was achieved in 31 (86%) patients in the MTZ/CTX group,
      compared with 28 (82%) patients in the T/C group (P=NS). Twenty-six patients were
      considered successfully treated on the final day of therapy in both the MTZ/CTX
      group (72%) and the T/C group (76%) (P=NS). There were no significant differences
      in primary or secondary measures of success between the 2 groups. No single or
      multiple baseline factors predicted treatment success or failure. No patient
      experienced adverse events considered related to study medication. MTZ/CTX was
      associated with savings of $61.06 per hospital admission, or $2198.05 for all
      patients who received this combination. CONCLUSION: In this population of older
      males, once-daily MTZ/CTX was as well tolerated and effective as T/C in the
      treatment of diabetic lower-extremity infections and was associated with reduced
      institutional costs.

PMID- 15561651
TI  - Medication error reporting in long term care.
AB  - BACKGROUND: Medication errors are common causes of medical error in the long-term
      care (LTC) setting. Despite their frequency and potential clinical impact, most
      medication errors in LTC facilities remain unreported. Before better reporting
      systems can be developed to reduce clinically significant medication errors, it
      is necessary to understand how current medication error reporting systems
      function. OBJECTIVE: This study describes the medication use and medication error
      reporting processes, and characterizes the knowledge, attitudes, and beliefs
      about medication errors of the nursing staff at a single LTC facility. METHODS:
      Three methods were used to characterize the medication use and medication error
      reporting processes and the nursing staff's perceptions about such errors. First,
      key elements and basic processes were defined through observation and semi
      structured interviews. Second, medication error reports were reviewed and
      summarized over a 21-month period. Third, nursing facility staff were surveyed
      about their knowledge, attitudes, and beliefs concerning medication errors.
      RESULTS: The medication use process in the LTC setting is similar to that
      employed in the acute care setting, consisting of 5 steps: prescribing,
      documenting, dispensing, administering, and monitoring. In the facility studied,
      an average of 4.7 medication error reports were submitted per month. Staff felt
      that half of all medication errors were identified and communicated informally
      through change-of-shift reports rather than through medication error reports.
      Most staff (85%) believed that disciplinary action was taken against the person
      who committed an error. CONCLUSIONS: The medication error policies and processes
      of the LTC facility studied were associated with a low frequency of formal
      reporting, a narrow perspective on the sources of error, and concerns about
      disciplinary action. Research is needed to better identify errors, develop
      interventions that broaden the monitoring perspective to include all health care
      professionals, reduce the work of reporting, standardize the information
      collected, and create an institutional atmosphere of participation rather than
      punishment.

PMID- 15561652
TI  - Intracerebral hemorrhage associated with use of an imported medication.
AB  - INTRODUCTION: The importation of medications is strongly discouraged in the
      United States. However, with the cost of prescription medications on the rise, an
      increasing number of patients are seeking alternative ways of obtaining drugs.
      Although medication errors involving imported drugs have been described in the
      literature, there is little available information on the prevalence of such
      problems. CASE SUMMARY: A 74-year-old woman who had been taking warfarin therapy
      for >2 years presented to the emergency department with new-onset headache. She
      was found to have a small subdural hematoma on computed tomography and a
      prothrombin time >120 seconds. Warfarin was stopped and anticoagulation was
      corrected with fresh frozen plasma. At follow-up testing, the international
      normalized ratio (INR) continued to be >2 despite vitamin K therapy and the
      patient's insistence that she had discontinued warfarin. Further evaluation by a
      hematologist detected warfarin in the blood. Subsequent inspection of her
      medications revealed unmarked white tablets labeled "phenytoin" that had been
      dispensed by a pharmacy in another country. The INR normalized after these
      tablets were discarded and a new prescription for phenytoin was started.
      DISCUSSION: Application of the Naranjo scale to this case suggested a high
      likelihood of an adverse drug reaction (ADR). Potential causes of the ADR
      included the placement of warfarin in a bottle mislabeled "phenytoin" and
      contamination of phenytoin with warfarin. CONCLUSIONS: Obtaining medications from
      pharmacies in or by mail order from other countries means that patients miss the
      opportunity to ask questions and receive counseling from a pharmacist. Physicians
      and pharmacists should inspect patients' medications to ensure product legitimacy
      and confirm that the indications, dispensing, and labeling are accurate.

PMID- 15561655
TI  - Making a difference.

PMID- 15561656
TI  - Limited obstetric ultrasound examinations: competency and cost.

PMID- 15561657
TI  - Mothers' decisions to change from formula to mothers' milk for very-low-birth
      weight infants.
AB  - OBJECTIVE: The purpose of this study was to examine maternal decisions about
      providing milk for a very-low-birth-weight (VLBW) infant, when the initial
      maternal intent was to formula-feed. DESIGN: Using prospective, purposive
      sampling, semistructured interviews were conducted with 21 of 23 eligible mothers
      over a 9-month period. Audio-recorded data were transcribed verbatim, coded,
      categorized, and subjected to dimensional analysis. SETTING: The study took place
      in a 52-bed, tertiary urban neonatal intensive-care unit. PATIENTS/PARTICIPANTS:
      Mean maternal age was 26.5 years (range = 18-38), and mean infant birth weight
      and gestational age were 705.4 g (range = 504-1,310), and 25.8 weeks (range = 23
      33), respectively. Of the 21 mothers, 76% were African American or Latina; 62%
      were low income. MAIN OUTCOME MEASURES: We evaluated mothers' initial reasons for
      selecting formula and changing the decision to provide their milk, whether they
      were made to feel guilty or coerced, the processes of establishing and
      maintaining lactation, and breastfeeding outcomes at 1-month postbirth. RESULTS:
      Mothers initially chose formula because they had no breastfeeding role models and
      were fearful of pain and lifestyle modifications. They changed this decision
      after the nurse or physician talked with them about the health benefits for their
      infant. Of the 21 women, all denied feeling pressured, coerced, or guilty about
      the decision change, and all identified rewards to themselves and their infants.
      All mothers provided milk for greater than or equal to 30 days, 19 went on to
      feed at breast, and 2 became certified breastfeeding peer counselors for the Rush
      Mothers' Milk Club. CONCLUSION: These findings underscore the role of nurses and
      physicians in providing evidence-based information about mothers' milk and
      indicate that sharing this knowledge does not make mothers of VLBW infants feel
      pressured, coerced, or guilty.

PMID- 15561658
TI  - Tub bathing versus traditional sponge bathing for the newborn.
AB  - OBJECTIVE: To compare selected effects of tub bathing versus traditional sponge
      bathing in healthy, term newborns and their mothers' ratings of pleasure and
      confidence with the bath. DESIGN: Randomized controlled study. SETTING: The
      maternity unit of an eastern Canadian hospital. PARTICIPANTS: One hundred two
      mother-baby pairs were randomly assigned to an experimental tub bath or a sponge
      bath control group. INTERVENTIONS: Fifty-one newborns were tub bathed and 51
      sponge bathed according to the study protocols for their initial and one
      additional bath. MAIN OUTCOME MEASURES: (a) Newborn temperature stability was
      assessed by recording axillary temperatures pre- and postbath, (b) umbilical cord
      healing was identified by daily observations and infection control surveillance,
      (c) infant contentment was quantified by applying the Brazelton Neonatal
      Behavioral Assessment Scale, and (d) maternal pleasure with the bath and
      confidence with bathing at discharge were self-rated on a 5-point scale. RESULTS:
      Tub-bathed babies experienced significantly less temperature loss (t = 4.79, p =
      .00) and were significantly more content (t = -6.48, p = .00) than were those who
      were sponge bathed. No differences in cord healing scores were found. Mothers of
      tub bathed babies rated their pleasure with the bath significantly higher than
      did mothers of sponge bathed babies (t = 4.15, p = .00). No differences in
      maternal confidence were noted. CONCLUSIONS: Tub bathing is a safe and
      pleasurable alternative to sponge bathing in healthy, term newborns.

PMID- 15561659
TI  - Reevaluation of Friedman's Labor Curve: a pilot study.
AB  - OBJECTIVE: To reevaluate the average length of each phase/stage of labor for
      multiparous and primiparous women in North America who received no regional
      anesthesia or oxytocin augmentation or induction, to describe a range of labor
      lengths associated with good childbirth outcomes, and to determine if there is a
      consensus among labor and delivery nurse managers responding to the survey
      regarding the need to revise Friedman's Labor Curve. DESIGN: This pilot study
      used a descriptive and anonymous cross-sectional survey design. Surveys were
      mailed to 500 maternity care agencies in the United States, Canada, and Mexico
      with a return rate of 17.8% (n = 89). Each participating agency was asked to
      submit five patient cases to be included in the analysis. SAMPLE AND SETTING: The
      sample of patient cases (n = 419) was drawn from randomly selected maternity care
      agencies throughout North America representing all sizes of agencies and
      geographic locations. The cases submitted for analysis represented women 14 to 44
      years of age with varying ethnicities who received no regional anesthesia or
      oxytocin augmentation or induction. Twenty-three percent of the women in the
      sample (n = 97) were primigravidas. RESULTS: The average length of labor for
      primiparous and multiparous women today is similar to the average length of labor
      described by Friedman in 1954. However, a wider range of "normal" was found in
      cases included in the current study. Primiparous women remained in the first
      stage of labor for up to 26 hours and the second stage of labor up to 8 hours
      with no adverse effects to mother or infant. Multiparous women remained in the
      first stage of labor for up to 23 hours and the second stage of labor for up to
      4.5 hours with good birth outcomes. In addition, 87.6% of nurse managers
      responding to the survey believed that Friedman's Labor Curve should be revised
      to meet the needs of current patient populations, technological advances, and
      nursing responsibilities. CONCLUSIONS: This study suggests that the parameters to
      determine if a labor is progressing satisfactorily may need to be expanded. With
      the availability of technology to assess maternal and fetal well-being, labor
      should be allowed to progress past the rigid 2-hour time limit for the second
      stage of labor artificially imposed on women in some childbirth settings. More
      emphasis should be placed on the nursing assessment techniques used to reassure
      the family and health care practitioners that labor is progressing safely and the
      nursing interventions that may have an impact on the length of each stage of
      labor.

PMID- 15561660
TI  - Refugee women's reproductive health in early resettlement.
AB  - OBJECTIVE: To describe reproductive health needs and screening rates for breast
      and cervical cancer for newly arrived (less than 90 days) refugee women in the
      United States. DESIGN: A retrospective study of existing medical charts from 1996
      to 2000. SETTING: Refugee health screening clinic, central Texas. PATIENTS:
      Refugee women (n = 283) newly arrived in the United States from Cuba (31.1%),
      Bosnia (26.1%), Vietnam (24.7%), and other countries (18.0%); age range = 18 to
      74 years, mean age = 34.4 years. MAIN OUTCOME MEASURES: Frequency of reproductive
      health problems and breast and cervical cancer screening rates. RESULTS: Twenty
      five percent of women in the sample were pregnant or had a reproductive health
      problem. A significant percentage older than 40 (86%) had never had a mammogram
      when compared to American women of the same age (33%). Only 24% reported having
      had a Pap test within the previous 3 years. CONCLUSIONS: The risk of not
      receiving adequate reproductive health care is higher among newly arrived refugee
      women compared to nonrefugee women in the United States. For refugee women to
      enjoy optimum health, their individual needs and health care system issues must
      be addressed.

PMID- 15561661
TI  - Postpartum emotional distress in mothers with multiple sclerosis.
AB  - OBJECTIVE: To determine the impact of multiple sclerosis (MS)-related symptoms
      and both received social support and perceived deficits in social support on
      emotional distress in mothers with MS at 1, 3, and 6 months postpartum. DESIGN:
      Longitudinal correlation descriptive study. SETTING: Community-residing women in
      North America. PARTICIPANTS: Convenience sample of 174 postpartum mothers with
      MS. METHOD: Mothers completed the MS-Related Symptom Scale and Postpartum Support
      Questionnaire at 1, 3, and 6 months postpartum. Bivariate correlations and
      hierarchical regression analyses determined relationships between the dependent
      variable, emotional distress, and independent variables: participant
      characteristics, MS-related symptoms, and social support. RESULTS: The authors
      found moderately strong positive correlations between MS-related symptoms and
      emotional distress at each assessment. Significant negative correlations existed
      between received social support and emotional distress at 1 month but not at 3
      and 6 months. Significant positive correlations existed between MS-related
      symptoms and social support deficits at each assessment. Explained variance in
      emotional distress across the three assessments ranged between 2% and 4% for
      participant characteristics, 49% and 60% for MS-related symptoms, 2% and 7% for
      social support, and 57% and 66% for total variance. CONCLUSION: MS-related
      symptoms created considerable emotional distress in mothers that was minimally
      alleviated by the support given them. In fact, many needed more support than they
      received.

PMID- 15561662
TI  - Effects of spirituality and psychosocial well-being on health risk behaviors in
      Appalachian pregnant women.
AB  - OBJECTIVE: To determine the relationships of spirituality and psychosocial well
      being to health risk behaviors in pregnant Appalachian women. METHOD: Descriptive
      study of 120 women between 16 and 28 weeks of pregnancy. The instruments used
      were the Spiritual Perspective Scale and religiosity items from the Jarel Well
      Being Scale. Psychosocial well-being was measured by the Prenatal Psychosocial
      Profile. Four items measured health risk behaviors. RESULTS: Higher levels of
      spirituality (spiritual perspective and religiosity) were significantly
      correlated with greater satisfaction with social support, higher levels of self
      esteem, and decreased levels of smoking. Sociodemographic, psychosocial, and
      spiritual variables explained 25% of the variance in frequency of smoking, and in
      the logistic regression analysis, psychosocial stress was the only variable that
      significantly predicted substance use. CONCLUSION: Higher levels of spirituality
      and lower levels of stress are associated with decreased health risk behaviors
      among pregnant women from Appalachia. Increasing spiritual resources and
      decreasing stress during pregnancy offer the potential to improve health
      promotion efforts in pregnancy with women from Appalachia.

PMID- 15561663
TI  - Childbirth experiences of professional Chinese Canadian women.
AB  - OBJECTIVE: To explore the connections between culture and expectations
      surrounding the childbirth experience for professional Chinese Canadian women.
      DESIGN: Descriptive and qualitative, using ethnographic interview. SETTING: Women
      were recruited from a community health care center in metropolitan Toronto.
      PARTICIPANTS: Six professional Chinese Canadian women who had experienced at
      least one childbirth. RESULTS: The respondents described adherence to many
      traditional values, beliefs, and practices throughout the pregnancy and
      childbirth experience. However, some practices were modified to address
      functioning in a context that could not support full expression of cultural
      traditions. Recent immigration to Canada was associated with less adherence to
      traditional Chinese rituals and beliefs. CONCLUSION: Nurses cannot make
      assumptions about who will use traditional cultural practices or about the
      circumstances in which they are relevant. Nurses need to be aware of cultural
      expectations so they can provide culturally competent care, but they should also
      be aware of how to engage in discussions to clarify individual patient
      priorities.

PMID- 15561664
TI  - Nurses' views on their role in genetics.
AB  - OBJECTIVE: To determine the views of nurses about their roles in genetics.
      DESIGN: A descriptive study. SETTING: Two university hospitals in Ankara, Turkey.
      PARTICIPANTS: From a population of 1,717 nurses, 313 were selected by using the
      stratified random sampling method. Two hundred seventy nurses agreed to
      participate. MAIN OUTCOME MEASURE: Nurses' viewpoints on their role in genetics.
      RESULTS: Nurses defined their roles in genetics as gathering family history,
      providing information about a genetic test including its duration and risks, and
      providing counseling and psychological support. More graduates of baccalaureate
      degree nursing programs were in favor of nurses' roles in genetics than were
      graduates of lower educational level. Nurses reported that their knowledge of
      basic genetics is insufficient and that they need additional training. The
      majority of nurses were not aware of the possible risks and harms of genetic
      information for the individual, suggesting a very important point of ethical
      lack. CONCLUSION: The results of this study demonstrate a need for educational
      preparation for nurses in both genetics and ethics. Nurses could assume their
      potential roles if their educational needs were met.

PMID- 15561665
TI  - Impact of prior perinatal loss on subsequent pregnancies.
AB  - OBJECTIVE: To evaluate the influence of previous perinatal loss on depressive
      symptoms, pregnancy-specific anxiety, and prenatal attachment for parents during
      subsequent pregnancies. DESIGN: Cross-sectional, survey design. PARTICIPANTS:
      Forty expectant couples who experienced a prior perinatal loss. MEASURES:
      Influence of loss (Impact of Event Scale [IES]), depressive symptoms (Center for
      Epidemiologic Studies-Depression Scale [CES-D]), pregnancy-specific anxiety
      (Pregnancy Outcome Questionnaire [POQ]), and prenatal attachment (Prenatal
      Attachment Inventory [PAI]). RESULTS: Mothers reported higher levels of
      depressive symptoms, pregnancy-specific anxiety, and prenatal attachment than
      fathers did. Forty-five percent of mothers and 23% of fathers had CES-D scores
      greater than or equal to 16 indicating high risk for depression. Eighty-eight
      percent of mothers and 90% of fathers reported elevated stress related to the
      prior loss (IES scores greater than or equal to 19). The impact of the previous
      perinatal loss was moderately correlated with depressive symptoms as well as
      pregnancy-specific anxiety. There was no relationship between the psychological
      distress in pregnancy after perinatal loss and prenatal attachment. CONCLUSIONS:
      The extent to which the impact of the prior loss increased parents' stress in the
      current pregnancy influenced their psychological distress. These findings should
      heighten awareness of the mixture of hope and fear expectant parents experience
      during pregnancies subsequent to perinatal loss.

PMID- 15561666
TI  - Grief, anxiety, stillbirth, and perinatal problems: healing with kangaroo care.
AB  - A young, anxious mother's first pregnancy was eclamptic, her placenta was
      underperfused, and her son was stillborn. She carried grief, guilt, anxiety, and
      hypervigilance into her next preeclamptic pregnancy, birth (of her small-for
      dates son), and early postpartum period. When breastfeeding difficulties
      developed, the authors intervened with three consecutive (skin-to-skin)
      breastfeedings. During the first skin-to-skin breastfeeding, the mother stopped
      crying, shared self-disparaging emotions, and then began relaxing and "taking-in"
      her new baby. Breastfeeding continues at 1 year.

PMID- 15561667
TI  - Positive pregnancy outcomes in Mexican immigrants: what can we learn?
AB  - OBJECTIVE: To provide an integrated review of the literature of potential
      explanations for better than expected pregnancy outcomes in Mexican immigrants,
      focusing on socioeconomics, social support, desirability of pregnancy, nutrition,
      substance use, religion, acculturation, and prenatal care. DATA SOURCES:
      Computerized searches of MEDLINE and CINAHL databases, as well as reference lists
      from published articles on low birth weight and prematurity in immigrants and
      acculturation in immigrants from January 1989 to December 2002. Search terms were
      Mexican immigrant women, childbearing, and pregnancy outcome, and only English
      language articles were reviewed. STUDY SELECTION: Literature was selected from
      refereed publications in the areas of nursing, medicine, public health, family,
      and sociology. DATA EXTRACTION: Data were extracted using keywords pertinent to
      pregnancy outcome in Mexican immigrants. DATA SYNTHESIS: Despite having many of
      the risk factors for poor pregnancy outcomes, Mexican immigrants have superior
      birth outcomes when compared to U.S.-born women. Social support, familism,
      healthy diet, limited use of cigarettes and alcohol, and religion may play a role
      in improved outcomes. The superior outcomes diminish with the process of
      acculturation as the individual adapts to her new culture. CONCLUSIONS: Low birth
      weight and prematurity are public health concerns in the United States. Through
      further study of the factors that lead to superior birth outcomes among Mexican
      immigrant women, rates of low birth weight and prematurity in the United States
      may be reduced.

PMID- 15561668
TI  - Nutrition in women and newborns.

PMID- 15561669
TI  - Increasing activity to reduce obesity in adolescent girls: a research review.
AB  - OBJECTIVE: To provide a systematic review of physical activity intervention
      research conducted with adolescent girls (12-19 years of age and/or in middle or
      high school) in the United States and Canada during the past two decades. DATA
      SOURCES: Published articles in English were identified in searches using MEDLINE,
      Cumulative Index to Nursing and Allied Health Literature, PsycLIT, EMBASE,
      Science Citation Index, and the Cochrane Controlled Trials Register, with the
      keywords adolescent health, obesity, physical activity, and exercise, between the
      dates of May 1980 and November 2003. STUDY SELECTION: Research studies with
      interventions that started within the adolescent time period. Only 7 studies met
      the inclusion criteria. DATA EXTRACTION: The publication year, sample
      description, study design, interventions used, and outcomes were extracted from
      each study. DATA SYNTHESIS: The 7 studies were published between 1989 and 2003,
      included girls and boys in the overall sample (no studies with girl-only
      samples), used randomized controlled trial or quasi-experimental designs, and
      included multicomponent interventions. Body mass index, fitness levels, exercise,
      and weight were measured as outcomes. CONCLUSIONS: Although the results were not
      consistent across studies, they suggest that school-based, multicomponent
      interventions that were also designed to decrease sedentary behavior were
      effective in increasing physical activity in adolescent girls. Future research
      should focus on determinants of long-term adherence and the duration and
      intensity of interventions necessary to prevent obesity in adolescent girls.

PMID- 15561670
TI  - Prenatal nutrition and birth outcomes.
AB  - The complex relationship between maternal nutritional and birth outcomes
      emphasizes the need for consistent and thorough assessments of women's diet
      throughout pregnancy and individualized nutritional education to promote positive
      birth outcomes. The purpose of this article is to examine the influence of
      prenatal nutrition on birth outcomes, describe research on the effects of macro-
      and micronutrients on birth outcomes, and discuss strategies for monitoring diet
      and implementing nutrition education during pregnancy.

PMID- 15561671
TI  - Obesity and nutrition in women throughout adulthood.
AB  - Nutritional challenges are particularly relevant to women. Almost 62% of women
      are overweight; of these women, 33% are obese. The incidence of obesity is even
      greater in non-Hispanic Black and Mexican American women. Women who are
      overweight or obese experience a greater number of adverse health outcomes,
      including an increased incidence of cardiovascular disease and breast and colon
      cancer. Dietary patterns influence health outcomes, with a heart-healthy pattern
      having the most positive health outcomes. Health care providers should encourage
      women to consume a diet high in fruits and vegetables and low in total and
      saturated fats.

PMID- 15561672
TI  - Proventriculitis in broiler chickens: immunohistochemical characterization of the
      lymphocytes infiltrating the proventricular glands.
AB  - Broiler chickens with transmissible proventriculitis have severe lymphocytic
      infiltration of the proventricular glands. The distribution of T cells and B
      cells in these infiltrates was studied histopathologically, and their identity
      was confirmed immunohistochemically (CD3, CD4, CD8, and B cells). To reproduce
      this disease, 1-day-old commercial boilers were orally gavaged with homogenized
      proventriculi from broilers with proventriculitis. Resulting lesions were
      examined at both acute (7 days postinoculation [i]) and chronic (14 and 21 dpi)
      time points. Lymphocytic infiltrates in the proventricular glands and the mucosal
      lamina propria were present at all time points and were most prominent and
      demarcated at 14 dpi. T and B lymphocytes were present during acute and chronic
      proventriculitis, but their distribution varied within the glands. Lymphocytic
      infiltrates in the proventricular glands and in the lamina propria were
      predominantly CD3+T cells, and most of these were also CD8+. B cells and CD4+ T
      cells formed aggregates in chronic proventriculitis. Thus, both cell-mediated and
      humoral immune responses are induced during transmissible proventriculitis, and
      the cell-mediated immune response is morphologically greater.

PMID- 15561673
TI  - Gene regulation in hematopoiesis: new lessons from thalassemia.
AB  - Over the past fifty years, many advances in our understanding of the general
      principles controlling gene expression during hematopoiesis have come from
      studying the synthesis of hemoglobin. Discovering how the alpha and beta globin
      genes are normally regulated and documenting the effects of inherited mutations
      which cause thalassemia have played a major role in establishing our current
      understanding of how genes are switched on or off in hematopoietic cells.
      Previously, nearly all mutations causing thalassemia have been found in or around
      the globin loci, but rare inherited and acquired trans-acting mutations are being
      found with increasing frequency. Such mutations have demonstrated new mechanisms
      underlying human genetic disease. Furthermore, they are revealing new pathways in
      the regulation of globin gene expression which, in turn, may eventually open up
      new avenues for improving the management of patients with common types of
      thalassemia.

PMID- 15561674
TI  - Thalassemia.
AB  - New developments in the epidemiology, treatment and prognosis of thalassemia have
      dramatically altered the approach to the care of affected patients, and these
      developments are likely to have an even greater impact in the next few years.
      Demographic changes have required an awareness and understanding of the unique
      features of thalassemia disorders that were previously uncommon in North America
      but are now seen more frequently in children and recognized more consistently in
      adults. New methods for measuring tissue iron accumulation and new drugs to
      remove excessive iron are advancing two of the most challenging areas in the
      management of thalassemia as well as other transfusion-dependent disorders.
      Improved survival of patients with thalassemia has given new importance to adult
      complications such as endocrinopathies and hepatitis that have a major impact on
      the quality of life. This chapter describes how these changes are redefining the
      clinical management of thalassemia. In Section I, Dr. Renzo Galanello describes
      recent advances in iron chelation therapy. Several new chelators are either
      licensed in some countries, are in clinical trials or are in the late stages of
      preclinical development. Some of these iron chelators, such as deferiprone (DFP)
      and ICL670, are orally active. Others, such as hydroxybenzyl-ethylenediamine
      diacetic acid (HBED) and starch deferoxamine, require parenteral administration
      but may be effective with less frequent administration than is currently required
      for deferoxamine. Chelation therapy employing two chelators offers the
      possibility of more effective removal of iron without compromising safety or
      compliance. Other strategies for chelation therapy may take advantage of the
      ability of particular chelators to remove iron from specific target organs such
      as the heart and the liver. In Section II, Dr. Dudley Pennell addresses cardiac
      iron overload, the most frequent cause of death from chronic transfusion therapy.
      The cardiac complications related to excessive iron may result from long-term
      iron deposition in vulnerable areas or may be due to the more immediate effects
      of nontransferrin-bound iron. Cardiac disease is reversible in some patients with
      intensive iron chelation therapy, but identification of cardiac problems prior to
      the onset of serious arrhythmias or congestive heart failure has proven
      difficult. New methods using magnetic resonance imaging (MRI) have recently been
      developed to assess cardiac iron loading, and studies suggest a clinically useful
      relationship between the results using these techniques and critical measures of
      cardiac function. Measurements such as T2* may help guide chelation therapy in
      individual patients and may also enhance the assessment of new chelators in
      clinical trials. The use of MRI-based technology also holds promise for wider
      application of non-invasive assessment of cardiac iron in the management of
      patients with thalassemia. In Section III, Dr. Melody Cunningham describes some
      of the important complications of thalassemia that are emerging as patients
      survive into adulthood. Hepatitis C infection is present in the majority of
      patients older than 25 years. However, antiviral therapy in patients with
      thalassemia has been held back by the absence of large clinical trials and
      concern about ribavirin-induced hemolysis. More aggressive approaches to the
      treatment of hepatitis C may be particularly valuable because of the additive
      risks for cirrhosis and hepatocellular carcinoma that are posed by infection and
      iron overload. Thrombosis is recognized with increasing frequency as a
      significant complication of thalassemia major and thalassemia intermedia, and
      pulmonary hypertension is now the focus of intense study. Risk factors for
      thrombosis such as splenectomy are being identified and new approaches to
      anticoagulation are being initiated. Pregnancies in women with thalassemia are
      increasingly common with and without hormonal therapy, and require a better
      understanding of the risks of iron overload and cardiac disease in the mother and
      exposure of the fetus to iron chelators. In Section IV, Dr. Elliott Vichinsky
      describes the dramatic changes in the epidemiology of thalassemia in North
      America. Hemoglobin E-beta thalassemia is seen with increasing frequency and
      poses a particular challenge because of the wide variability in clinical
      severity. Some affected patients may require little or no intervention, while
      others need chronic transfusion therapy and may be appropriate candidates for
      hematopoietic stem cell transplantation. Enhancers of fetal hemoglobin production
      may have a unique role in Hb E-beta thalassemia since a modest increase in
      hemoglobin level may confer substantial clinical benefits. Alpha thalassemia is
      also being recognized with increasing frequency in North America, and newborn
      screening for Hemoglobin Barts in some states is leading to early detection of Hb
      H disease and Hb H Constant Spring. New data clarify the importance of
      distinguishing these two disorders because of the increased severity associated
      with Hb H Constant Spring. The use of intrauterine transfusions to sustain the
      viability of fetuses with homozygous alpha thalassemia has created a new
      population of patients with severe thalassemia and has raised new and complex
      issues in genetic counseling for parents with alpha thalassemia trait.

PMID- 15561675
TI  - Sickle cell disease.
AB  - Much progress has been made during the past several decades in gaining
      understanding about the natural history of sickle cell disease and management
      approaches aimed at treating or even preventing certain disease complications.
      The characterization of the human genome now offers the opportunity to understand
      relationships regarding how gene polymorphisms as well as how environmental
      factors affect the sickle cell disease phenotype, i.e., the individual patient's
      overall clinical severity as well as their specific organ function. This chapter
      explores some of these recent advances in knowledge. In Section I, Dr. Michael
      DeBaun characterizes the problem of silent stroke in sickle cell disease,
      comparing and contrasting its clinical and neuroimaging features with overt
      stroke. Combined, these events affect virtually 40% of children with sickle cell
      anemia. New understanding of risk factors, associated clinical findings, and
      imaging technologies are impacting substantially on treatment options. The
      appreciable cognitive dysfunction and other sequelae of silent infarct demand
      more effective treatments and ultimate prevention. In Section II, Dr. Charles
      Quinn addresses the conundrum of why some patients with sickle cell disease do
      well whereas others fare poorly. Some risk factors have been known for years,
      based upon careful study of hundreds of patients by the Cooperative Study for
      Sickle Cell Disease and investigators studying the Jamaican newborn cohort. Other
      prognostic measures have only recently been defined. Dr. Quinn devotes special
      attention to stroke and chest syndrome as organ-related complications but also
      describes attempts to measure overall disease severity and to predict survival.
      Recently, investigators have attempted to predict factors responsible for early
      mortality in children and following onset of pulmonary hypertension in adults. In
      Section III, Dr. Martin Steinberg reviews pharmacologic approaches to sickle cell
      disease and the rationale for their use. In addition to the inhibition of
      hemoglobin S polymerization, newer targets have been defined during the past one
      to two decades. These include the erythrocyte membrane, changes in the red cell
      intracellular content (especially loss of water), endothelial injury, and free
      radical production. Hydroxyurea treatment attracted the greatest interest, but
      many uncertainties remain about its long-term benefits and toxicities. Newer
      "anti-sickling" agents such as decitabine and short-chain fatty acids also
      receive attention. Prevention of red cell dehydration, "anti-endothelial"
      therapy, and marshalling the potentially beneficial effects of nitric oxide are
      other new and exciting approaches.

PMID- 15561676
TI  - Immune-mediated hemolytic anemia.
AB  - Hemolytic anemia due to immune function is one of the major causes of acquired
      hemolytic anemia. In recent years, as more is known about the immune system,
      these entities have become better understood and their treatment improved. In
      this section, we will discuss three areas in which this progress has been
      apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the
      pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the
      biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked
      proteins on the cell surface) to the clinical manifestations, particularly
      hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the
      disorder in the face of marrow dysfunction insofar as it is known. His major
      emphasis is on innovative therapies that are designed to decrease the
      effectiveness of complement activation, since the lack of cellular modulation of
      this system is the primary cause of the pathology of the disease. He recounts his
      considerable experience with a humanized monoclonal antibody against C5, which
      has a remarkable effect in controlling the manifestations of the disease. Other
      means of controlling the action of complement include replacing the missing
      modulatory proteins on the cell surface; these studies are not as developed as
      the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry,
      genetics, and function of the Fc gamma receptors and their role in the
      pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic
      purpura due to IgG antibodies. He outlines the complex varieties of these
      molecules, showing how they vary in genetic origin and in function. These
      variations can be related to three-dimensional topography, which is known in some
      detail. Liganding IgG results in the transduction of a signal through the
      tyrosine-based activation motif and Syk signaling. The role of these receptors in
      the pathogenesis of hematological diseases due to IgG antibodies is outlined and
      the potential of therapy of these diseases by regulation of these receptors is
      discussed. In Section III, Dr. Wendell Rosse discusses the forms of autoimmune
      hemolytic anemia characterized by antibodies that react preferentially in the
      cold-cold agglutinin disease and paroxysmal cold hemoglobinuria (PCH). The former
      is due to IgM antibodies with a common but particular structure that reacts
      primarily with carbohydrate or carbohydrate-containing antigens, an interaction
      that is diminished at body temperature. PCH is a less common but probably
      underdiagnosed illness due to an IgG antibody reacting with a carbohydrate
      antigen; improved techniques for the diagnosis of PCH are described. Therapy for
      the two disorders differs somewhat because of the differences in isotype of the
      antibody. Since the hemolysis in both is primarily due to complement activation,
      the potential role of its control, as by the monoclonal antibody described by Dr.
      Hillmen, is discussed.

PMID- 15561677
TI  - Congenital and acquired neutropenia.
AB  - Our understanding of the pathogenesis of congenital and acquired neutropenia is
      rapidly evolving. New ground-breaking observations have identified the genes
      responsible for many of the congenital neutropenia syndromes and are also
      providing new insights into normal neutrophil commitment and differentiation.
      Acquired neutropenia remains a poorly understood syndrome, although new insights
      into its pathogenesis are also emerging, especially with regard to subsets of
      immune neutropenia. In Section I, Dr. Marshall Horwitz reviews the current
      understanding of the genetic basis, molecular pathology, and approaches to
      treatment of congenital neutropenia and cyclic hematopoiesis. Mutations in the
      ELA2 gene, which encodes for neutrophil elastase, cause cyclic hematopoiesis.
      ELA2 mutations are also the most common cause of congenital neutropenia, where
      their presence may equate with a more severe clinical course and higher frequency
      of leukemic progression. Emerging evidence indicates interrelatedness with
      Hermansky Pudlak syndrome and other disorders of neutrophil and platelet
      granules. In Section II, Dr. Nancy Berliner presents an overview of the clinical
      approach to the evaluation and treatment of acquired neutropenia. This includes a
      review of the pathogenesis of primary and secondary immune neutropenia, drug
      induced neutropenia, and non-immune chronic idiopathic neutropenia of adults.
      Studies used to evaluate patients for potential immune neutropenia are reviewed.
      Management issues, especially the use of granulocyte colony-stimulating factor (G
      CSF), are discussed. In Section III, Dr. Thomas Loughran, Jr., reviews the
      pathogenesis and clinical manifestations of large granular lymphocyte (LGL)
      leukemia. Possible mechanisms of neutropenia are discussed. In particular,
      discussion focuses on the relationship between LGL leukemia, rheumatoid disease,
      and Felty's syndrome, and the complex interplay of defects in neutrophil
      production, distribution, destruction, and apoptosis that underly the development
      of neutropenia in those syndromes.

PMID- 15561678
TI  - The molecular basis of leukemia.
AB  - Major strides have been made in our understanding of the molecular basis of adult
      and pediatric leukemias. More than one hundred disease alleles have been
      identified and characterized in cell culture and murine models of leukemia. In
      some instances, molecularly targeted therapies have been developed based on these
      insights that are currently in clinical trials, such as small molecule inhibitors
      of FLT3. In addition, it has recently been appreciated that, as with normal
      hematopoiesis, there is a hierarchical organization among leukemic cells that
      includes a rare population of leukemic stem cells that have properties of self
      renewal. Understanding the characteristics of these leukemic stem cells may
      provide new insights into leukemia therapies that target self-renewal pathways.
      In Section I, Dr. Craig Jordan reviews the data that supports the existence of a
      "leukemia stem cell." He provides an overview of the functional properties of
      leukemic stem cells, their relationship to hematopoietic stem cells, and the
      relevance of leukemic stem cells in other human malignancies including solid
      tumors. He briefly discusses what is known of the pathways that regulate
      properties of self-renewal. Dr. Gary Gilliland provides an overview of the
      genetics of adult leukemias in Section II and ongoing genome-wide strategies for
      discovery of new disease alleles. He describes the clinical and therapeutic
      implications of these findings and provides examples of bench-to-bedside
      translation of molecularly targeted therapies for AML, including the use of FLT3
      inhibitors. In Section III, Dr. Carolyn Felix reviews recent advances in our
      understanding of the genetics and therapy of pediatric leukemias. She provides an
      overview of leukemias that are common in pediatric malignancies but rarely
      observed in adults, including the TEL-AML1 (ETV6-RUNX1) fusion associated with
      pediatric B-cell ALL, the OTT-MAL fusion associated with infant megakaryoblastic
      leukemia, PTPN11 mutations in juvenile myelomonocytic leukemia, and MLL fusion
      genes in leukemogenesis, among others.

PMID- 15561679
TI  - Acute myeloid leukemia.
AB  - Advances in our understanding of the pathophysiology of acute myeloid leukemia
      (AML) have not yet led to major improvements in disease-free and overall survival
      of adults with this disease. Only about one-third of those between ages 18-60 who
      are diagnosed with AML can be cured; disease-free survival is rare and current
      therapy devastating in older adults. In this chapter, challenges in the
      management of the adult with AML are discussed, including ongoing questions
      concerning the optimal choice of induction and postremission therapy such as the
      rationale for and role of allogeneic and autologous stem cell transplantation in
      a variety of settings, the special considerations pertaining to the older
      patient, and the development of new, so-called targeted therapies. In Section I,
      Dr. Richard Stone reviews state-of the-art therapy in AML in the era of change
      from a morphological to a genetically based classification system. Questions
      being addressed in ongoing randomized cooperative group trials include
      anthracycline dose during induction, the efficacy of drug-resistance modulators,
      and the utility of pro-apoptotic agents such as the anti-bcl-2 antisense
      oligonucloetide. Developmental therapeutics in AML include drug resistance
      modulation, anti-angiogenic strategies, immunotherapy, and signal transduction
      active agents, particularly the farnesyl transferase inhibitors as well as those
      molecules that inhibit the FLT3 tyrosine kinase, activated via mutation in 30% of
      patients. In Section II Dr. Margaret O'Donnell discusses the role of stem cell
      transplantation in AML. Several advances including expanded donor pools, the
      movement toward peripheral blood stem cell collection, newer immunosuppressive
      drugs and antifungals, and particularly the advent of nonmyeloablative transplant
      have made the allogeneic option more viable. The subset-specific role for high
      dose chemotherapy with autologous stem cell support and/or for allogeneic
      transplant in AML patients in first remission is outlined. Although preconceived
      notions about the role of transplant abound, the clinical data supporting a risk
      adapted approach are covered. Finally, guidance concerning the use of
      nonmyeloablative or reduced-intensity allogeneic transplantation is provided. In
      Section III Dr. Mikkael Sekeres reviews the approach to the older patient with
      AML. Unique biological and therapeutic considerations make AML in this age group
      a vastly different disease than that in younger adults. The outcome data,
      including the role of specific anthracylines, hematopoietic growth factors, and
      drug-resistance modulators, are summarized. Communicating with older adults with
      AML and their families regarding selection of the optimal treatment strategy,
      often a stark choice between induction chemotherapy and palliative care, is
      covered.

PMID- 15561680
TI  - Childhood and adolescent lymphoid and myeloid leukemia.
AB  - Remarkable progress has been made in the past decade in the treatment and in the
      understanding of the biology of childhood lymphoid and myeloid leukemias. With
      contemporary improved risk assessment, chemotherapy, hematopoietic stem cell
      transplantation and supportive care, approximately 80% of children with newly
      diagnosed acute lymphoblastic leukemia and 50% of those with myeloid neoplasm can
      be cured to date. Current emphasis is placed not only on increased cure rate but
      also on improved quality of life. In Section I, Dr. Ching-Hon Pui describes
      certain clinical and biologic features that still have prognostic and therapeutic
      relevance in the context of contemporary treatment programs. He emphasizes that
      treatment failure in some patients is not due to intrinsic drug resistance of
      leukemic cells but is rather caused by suboptimal drug dosing due to host
      compliance, pharmacodynamics, and pharmacogenetics. Hence, measurement of minimal
      residual disease, which accounts for both the genetic (primary and secondary)
      features of leukemic lymphoblasts and pharmacogenomic variables of the host, is
      the most reliable prognostic indicator. Finally, he contends that with optimal
      risk-directed systemic and intrathecal therapy, cranial irradiation may be
      omitted in all patients, regardless of the presenting features. In Section II,
      Dr. Martin Schrappe performs detailed analyses of the prognostic impact of
      presenting age, leukocyte count, sex, immunophenotype, genetic abnormality, early
      treatment response, and in vitro drug sensitivity/resistance in childhood acute
      lymphoblastic leukemia, based on the large database of the Berlin-Frankfurt
      Munster consortium. He also succinctly summarizes the important treatment
      components resulting in the improved outcome of children and young adolescents
      with this disease. He describes the treatment approach that led to the improved
      outcome of adolescent patients, a finding that may be applied to young adults in
      the second and third decade of life. Finally, he believes that treatment
      reduction under well-controlled clinical trials is feasible in a subgroup of
      patients with excellent early treatment response as evidenced by minimal residual
      disease measurement during induction and consolidation therapy. In Section III,
      Dr. Raul Ribeiro describes distinct morphologic and genetic subtypes of acute
      myeloid leukemia. The finding of essentially identical gene expression profiling
      by DNA microarray in certain specific genetic subtypes of childhood and adult
      acute myeloid leukemia suggests a shared leukemogenesis. He then describes the
      principles of treatment as well as the efficacy and toxicity of various forms of
      postremission therapy, emphasizing the need of tailoring therapy to both the
      disease and the age of the patient. Early results suggest that minimal residual
      disease measurement can also improve the risk assessment in acute myeloid
      leukemia, and that cranial irradiation can be omitted even in those with central
      nervous-system leukemia at diagnosis. In Section IV, Dr. Charlotte Niemeyer
      describes a new classification of myelodysplastic and myeloproliferative diseases
      in childhood, which has greatly facilitated the diagnosis of myelodysplastic
      syndromes and juvenile myelomonocytic leukemia. The recent discovery of somatic
      mutations in PTPN11 has improved the understanding of the pathobiology and the
      diagnosis of juvenile myelomonocytic leukemia. Together with the findings of
      mutations in RAS and NF1 in the other patients, she suggests that pathological
      activation of RAS-dependent pathways plays a central role in the leukemogenesis
      of this disease. She then describes the various treatment approaches for both
      juvenile myelomonocytic leukemia and myelodysplastic syndromes in the US and
      Europe, emphasizing the differences between childhood and adult cases for the
      latter group of diseases. She also raises some controversial issues regarding
      treatment that will require well-controlled international clinical trials to
      address.

PMID- 15561681
TI  - Chronic myelogenous leukemia and myeloproliferative disease.
AB  - In Section I, Dr. Stephen O'Brien reviews the latest data on the clinical use of
      imatinib (STI571, Gleevec, Glivec) in CML. His review focuses on the use of
      imatinib in newly diagnosed chronic phase patients and summarizes cytogenetic and
      molecular response data, as well as use of the agent at high doses and in
      combination with other drugs. A brief summary of the prospective international
      Phase III studies that are currently ongoing is also provided, and the issues of
      resistance and definition of suboptimal therapeutic response are also covered.
      Finally, therapeutic decision-making and treatment strategy are considered. In
      Section II, Dr. Ayalew Tefferi considers the latest developments in the biology
      and therapy of myeloid metaplasia/myelofibrosis. Dr. Tefferi covers what is
      currently understood of the biology of the disease and reviews established
      therapies for the condition as well as novel agents that are being used in
      clinical trials. The development of optimal management strategies for the disease
      is considered. In Section III, Dr. Peter Valent reviews the classification of
      mast cell proliferative disorders and covers the clinical and pathological
      presentation of this group of neoplasms. He reviews the state-of-the-art
      regarding the molecular biology of mastocytosis along with diagnostic criteria
      and novel treatment concepts.

PMID- 15561682
TI  - Chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is one of the most commonly diagnosed
      leukemias managed by practicing hematologists. For many years patients with CLL
      have been viewed as similar, with a long natural history and only marginally
      effective therapies that rarely yielded complete responses. Recently, several
      important observations related to the biologic significance of V(H) mutational
      status and associated ZAP-70 overexpression, disrupted p53 function, and
      chromosomal aberrations have led to the ability to identify patients at high risk
      for early disease progression and inferior survival. Concurrent with these
      investigations, several treatments including the nucleoside analogues, monoclonal
      antibodies rituximab and alemtuzumab have been introduced. Combination of these
      therapies in clinical trials has led to high complete and overall response rates
      when applied as initial therapy for symptomatic CLL. Thus, the complexity of
      initial risk stratification of CLL and treatment has increased significantly.
      Furthermore, when these initial therapies do not work, approach of the CLL
      patient with fludarabine-refractory disease can be quite challenging. This
      session will describe the natural history of a CLL patient with emphasis on
      important decision junctures at different time points in the disease. In Section
      I, Dr. Stephan Stilgenbauer focuses on the discussion that occurs with CLL
      patients at their initial evaluation. This includes a review of the diagnostic
      criteria for CLL and prognostic factors utilized to predict the natural history
      of the disease. The later discussion of risk stratification focuses on molecular
      and genomic aberrations that predict rapid progression, poor response to therapy,
      and inferior survival. Ongoing and future efforts examining early intervention
      strategies in high risk CLL are reviewed. In Section II, Drs. Ian Flinn and Jesus
      G. Berdeja focus on the discussion of CLL patients when symptomatic disease has
      developed. This includes an updated review of monotherapy trials with nucleoside
      analogs and recent trials that have combined these with monoclonal antibodies
      and/or alternative chemotherapy agents. Appropriate application of more
      aggressive therapies such as autologous and allogeneic immunotherapy and less
      aggressive treatments for appropriate CLL patient candidates are discussed. In
      Section III, Dr. John Byrd focuses on the discussion that occurs with CLL
      patients whose disease is refractory to fludarabine. The application of genetic
      risk stratification in choosing therapy for this subset of patients is reviewed.
      Available data with conventional combination based therapies and monoclonal
      antibodies are discussed. Finally, alternative promising investigational
      therapies including new antibodies, kinase inhibitors (CDK, PDK1/AKT, PKC) and
      alternative targeted therapies (DNA methyltransferase inhibitors, histone
      deacetylase inhibitors, etc.) are reviewed with an emphasis on the most promising
      agents for this patient population.

PMID- 15561683
TI  - Hodgkin's lymphoma: evolving concepts with implications for practice.
AB  - Hodgkin's lymphoma is a unique neoplasm of B lymphocytes. Recent data provide new
      understandings of the pathogenesis and options for staging and therapy of the
      disease. Three specific topics are addressed in this chapter. In Section I, Dr.
      Richard Ambinder reviews implications of the relationship of Epstein-Barr virus
      (EBV) and Hodgkin's lymphoma. This relation includes varying geographic
      epidemiologic associations, including varying associations with the clinical
      syndrome of infectious mononucleosis. There are plausible mechanisms, including
      processes initiated by viral proteins, by which EBV might lead to tumorigenesis.
      These mechanisms include promotion of genetic instability and alteration of
      normal processes of apoptosis. In addition to an epidemiologic association and
      potential role in pathogenesis, viral antigens may pose theoretical targets for
      anti-cancer therapies, including vaccination. In Section II, Dr. Sigrid
      Stroobants describes the potential role of positron emission tomographic (PET)
      scanning. By assessing differences in the metabolic activities of cancer cells,
      PET scanning may be superior to computerized tomographic scanning, which is
      limited to showing structural anatomical abnormalities. In patients with
      Hodgkin's and non-Hodgkin's lymphoma, PET scanning has been tested as an initial
      staging tool, to assess the rate of therapeutic response from a prognostic
      perspective, and to differentiate residual tumor from fibrotic masses in patients
      who have completed therapy. Particularly in assessing the nature of a residual
      mass seen with other post-therapeutic imaging modalities, PET scanning may
      provide unique information; very high negative predictive values have been
      reported. However, before this technology can be recommended for incorporation
      into standard management, properly conducted prospective trials are required to
      better evaluate the clinical utility of PET with respect to eventual patient
      outcomes. In Section III, Dr. Ralph Meyer reviews current data regarding the
      management of patients with limited-stage Hodgkin's lymphoma. Over the past
      decade, standard treatment has evolved to consist of combined-modality therapy
      that includes an abbreviated course of chemotherapy and involved-field radiation.
      As this therapy continues to include radiation therapy, patients will remain at
      risk of long-term toxicities that include the development of second cancers and
      cardiovascular events. These "late-effects" now account for more deaths than
      those attributed to progressive Hodgkin's lymphoma. Comparative data testing the
      role of chemotherapy alone are now available and demonstrate that omission of
      radiation therapy results in small but statistically significant reduction in
      disease control, but no detectable differences in overall survival. Further
      follow-up will clarify whether chemotherapy alone is the preferred treatment
      option; at present patients should be informed of the trade-offs involved in
      choosing between this option and combined modality therapy.

PMID- 15561684
TI  - Low-grade lymphoma.
AB  - Folicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma,
      shows considerable heterogeneity in its clinical behavior, representative of a
      biology that appears increasingly complex and diverse. As our knowledge of the
      molecular basis of FL increases, we strive for an integration between the bench
      and clinic that yields treatments based on our scientific understanding and
      biomarkers that allow us to prescribe treatment rationally. In Section I, Dr.
      Randy Gascoyne describes the histologic, cytogenetic and biologic features of FL
      that underlie its clinical variability. Key aspects of the pathologic diagnosis
      of FL that have particular relevance to the clinician are highlighted. A proposed
      model for follicular lymphomagenesis and diffuse large B cell lymphoma
      transformation has emerged and continues to evolve as the molecular story
      unfolds. A biologic basis for clinical outcome in FL also appears to be
      forthcoming. In Section II, Dr. Jane Winter addresses the complex process of
      selecting among the many treatment options for patients with FL. Previously a
      simple matter of deciding between oral or intravenous alkylators, clinicians and
      patients must now struggle to choose among vastly different approaches ranging
      from "watch and wait" to stem cell transplantation. The introduction of rituximab
      and radioimmunoconjugates is changing the treatment paradigm, but the optimal
      approach to integrating these and other new agents remains to be determined. At
      every decision point, the best approach is always a clinical trial. In Section
      III, Dr. Koen Van Besien provides a well-documented update on outcomes associated
      with autologous and allogeneic stem cell transplantation for FL. The results of
      trials of autologous stem cell transplantation in first remission and recent data
      supporting a role for graft purging are discussed. Based on the premise that a
      graft-versus-lymphoma effect is operative in FL, reduced-intensity allogeneic
      transplantation is the preferred approach in many cases, and recently reported
      results are summarized. Criteria for patient selection and the optimal role of
      transplantation in the overall therapeutic plan for the patient with FL are
      presented.

PMID- 15561685
TI  - Diffuse aggressive lymphoma.
AB  - The aggressive non-Hodgkin's lymphomas can be cured in more than half of the
      cases. However, there has been great variation in the results reported from
      individual clinical Phase II trials. This variation in result can be attributed
      to unrecognized heterogeneity in this group of diseases. Recent clinical and
      molecular studies have enabled us to define more homogenous population in which
      new therapies can be studied. For patients with advanced stages of diffuse large
      B cell lymphoma, a new standard of therapy exists. For patients with localized
      aggressive non-Hodgkin's lymphomas, heterogeneity in patient selection prevents
      us from defining a new standard of care. Finally, in mantle cell lymphoma, new
      opportunities in drug discovery may permit advances in the treatment of this
      uniformly fatal malignancy. In Section I, Dr. Richard Fisher reviews the
      development of combination chemotherapy for patients with advanced stage diffuse
      large B cell lymphoma. Because of great heterogeneity in patients enrolled in
      Phase II studies, large randomized Phase III studies were required in the 1980s
      to define CHOP has the standard of care. This heterogeneity has now been defined
      carefully in the international prognostic factor index and more recently by gene
      array studies. It will now need to be incorporated prospectively into studies or
      retrospectively analyzed to understand clinical trial results. The addition of
      rituximab to CHOP has now been demonstrated to improve survival in two large
      Phase III studies in elderly patients. A recently presented study in younger
      patients suggests a similar benefit. Thus CHOP/rituximab has become the
      established standard of care for all patients with advanced stage diffuse large B
      cell lymphoma. Other concepts being evaluated to further improve on these results
      include: dose intensification; initial treatment with chemotherapy plus
      allogeneic stem cell transplantation; and infusional chemotherapy. Finally, the
      status of the treatment for relapsed patients will be defined. In Section II, Dr.
      Thomas Miller defines the treatment for limited stage aggressive non-Hodgkin's
      lymphoma. Randomized trials have demonstrated the critical importance of initial
      chemotherapy for treatment of these patients. The amount of chemotherapy given
      needs to be increased for patients with bulky tumors. In most circumstances
      radiotherapy after the completion of chemotherapy has been shown to be
      advantageous. A modification of the international prognostic factor index for
      patients with early stage disease is presented to permit comparisons among
      different populations. Recently reported early-stage studies need to be analyzed
      in terms of the heterogeneity of the patients involved to understand the reported
      results. The addition of monoclonal antibodies, as well as radioimmunotherapy,
      are being tested in an effort to improve on the results for the poor prognosis
      patients. In Section III, Dr. Owen O'Connor describes the pathology
      immunophenotype and natural history of mantle cell lymphoma. Conventional
      treatment strategies with combination chemotherapy achieved objective responses
      in approximately half of the patients but no significant impact on survival. The
      addition to rituximab to CHOP chemotherapy or other treatment strategies appears
      to improve the remission rate; however, no major changes in survival have also
      been reported. Excellent single institution results have been reported with
      HyperCVAD plus rituximab regimen, which is currently being tested in a national
      cooperative group trial. The most excitement in this field currently relates to
      the variety of new agents which appear to have significant activity in relapsed
      patients with mantle cell lymphoma. This includes the proteosome inhibitor,
      bortezomib, which is shown to have approximately a 50% response rate with some
      CRs and reasonable durability in early single institution Phase II studies.
      Larger national multi-center trials are ongoing. In addition, agents such as
      thalidomide, flavopiridol, and piroxantrone will be reviewed.

PMID- 15561686
TI  - Multiple myeloma.
AB  - High-dose therapy with stem cell transplantation (SCT) and novel targeted
      therapies (thalidomide, its more potent analogues, and bortezomib) represent two
      approaches for overcoming resistance of multiple myeloma (MM) cells to
      conventional therapies. While it is now clear that dose-intensification improves
      the outcome in younger patients, long-term remissions are obtained in a minority
      of patients. Therefore, the impact of novel agents as part of front-line therapy
      is the objective of ongoing trials. Gene expression profiling (GEP) will help to
      improve the management of MM not only by identifying prognostic subgroups but
      also by defining molecular pathways that are associated with these subgroups and
      that are possible targets for future therapies. In Section I, Dr. John
      Shaughnessy describes recent data obtained with GEP of CD138-purified plasma
      cells from patients with MM. His group has already shown that overexpression of
      the Wnt signaling inhibitor DKK1 by MM plasma cells blocks osteoblast
      differentiation and contributes to the development of osteolytic bone lesions.
      Recent data allow identification of four subgroups of MM in which GEP is highly
      correlated not only with different clinical characteristics and outcome but also
      with different cytogenetic abnormalities. In addition, abnormal expression of
      only three genes (RAN, ZHX-2, CHC1L) is associated with rapid relapses. In the
      context of intensive therapy with tandem autotransplantations, this model appears
      to be more powerful than current prognostic models based on standard biologic
      variables and cytogenetics. Understanding why the dysregulation of these three
      genes is associated with a more aggressive behavior of the disease will help to
      define new therapeutic strategies. In Section II, Dr. Jean-Luc Harousseau
      presents recent results achieved with tandem autologous SCT (ASCT) and with
      reduced intensity conditioning (RIC) allogeneic SCT. ASCT is now considered as
      the standard of care in patients up to 65 years of age. The IFM (Intergroupe
      Francophone du Myelome) has recently shown that double ASCT is superior to single
      ASCT. Current results of three other randomized trials confirm that double ASCT
      is superior, at least in terms of event-free survival. However, patients with
      poor prognostic features do poorly even after tandem ASCT. Strategies to further
      improve the outcome of ASCT include more intensive therapies and the use of novel
      agents such as thalidomide and immunomodulatory analogs (IMiDs) or bortezomib.
      Results of allogeneic SCT remain disappointing in MM even with T cell-depleted
      grafts. Preliminary results of a strategy combining ASCT to reduce tumor burden
      and RIC allogeneic SCT are encouraging, although the follow-up is still short.
      However, again, patients with chromosome 13 deletions have poor results with RIC.
      Longer follow-up of ongoing multicentric studies will help to clarify the
      indications of RIC. In Section III, Dr. Paul Richardson summarizes current
      knowledge of novel targeted therapies in MM. A better understanding of
      interactions between MM cells and bone marrow stromal cells and of the signaling
      cascades whereby cytokines mediate proliferation, survival, drug resistance and
      migration of MM cells provide the rationale for testing novel agents in
      relapsed/refractory MM. Increased angiogenesis coupled with the known anti
      angiogenesis activity of thalidomide justified its use in refractory MM. The
      remarkable responses initially achieved prompted a number of clinical studies in
      different indications and the development of more potent IMIDs. Among them CC
      5013 (Revlimid) has been tested in Phase I/II studies and a randomized Phase III
      study has just been completed. Blockade of NF-kappa B using the proteasome
      inhibitor bortezomib (Velcade) may mediate anti-MM activity by inhibiting
      interleukin (IL)-6 production in stromal cells and other mechanisms of action
      have been shown in preclinical studies. Based on the promising results of the
      Phase II trial, a large randomized trial of bortezomib versus dexamethasone has
      been completed. Studies of bortezomib combined with other drugs are ongoing.
      Arsenic trioxide has a number of properties showing that it targets MM cells
      interacting with the microenvironment. Clinical studies are ongoing as well.
      Other agents in MM have already been or will probably be translated soon from the
      bench to the bedside.

PMID- 15561687
TI  - Amyloidosis and Waldenstrom's macroglobulinemia.
AB  - Primary systemic amyloidosis is an immunoglobulin light chain disorder that is
      1/5th as common as multiple myeloma. Amyloidosis is regularly seen in the
      practice of a hematologist and has recently undergone major advances in terms of
      the ability to evaluate responses as well as new therapeutic options that were
      not available when this topic was covered as an education session at the American
      Society of Hematology meeting 5 years ago. Waldenstrom macroglobulinemia (WM) is
      rarer than amyloidosis (1500 per year WM versus 3000 per year amyloid in the US),
      and recent consensus panels have established the definition of the disease, the
      diagnostic criteria, criteria for initiation of therapy and a new classification
      scheme. In this session, new developments in amyloid and macroglobulinemia, from
      suspicion of the diagnosis to treatment, are covered. In Section I, Dr. Morie
      Gertz answers four specific questions: (1) When should amyloidosis be suspected?
      (2) How does one heighten ones index of suspicion for amyloid? (3) How is the
      diagnosis confirmed and the type classified as primary? (4) What is the prognosis
      and how is it accurately assessed? Recent findings on cardiac biomarkers,
      presenting features and use of the free light chain assay are reviewed. Staging
      for amyloid and recently proposed criteria of response and progression are
      covered. In Section II, Dr. Giampaolo Merlini comprehensively reviews therapy of
      amyloidosis from the use of standard melphalan/prednisone to the recently
      described standard dose therapies including dexamethasone,
      thalidomide/dexamethasone, melphalan/dexamethasone and IV
      melphalan/dexamethasone. An extensive discussion of the role of high-dose therapy
      with stem cell reconstitution follows and includes patient selection, predictors
      of immediate morbidity and mortality, and survival expectation. Finally, a
      therapeutic strategy is proposed. In Section III, Drs. Steven Treon and Giampaolo
      Merlini review the most current information on WM. The consensus panel results
      and recommendations of the clinical pathologic definition of WM, the prognostic
      markers and the indications to initiate therapy in WM, the uniform response
      criteria in WM and available treatments for the disease are reviewed. Drs. Treon
      and Merlini cover recently published treatment protocols that use rituximab,
      purine nucleoside analogs, and alkylating agents. The current data on
      thalidomide, alpha interferon, and high-dose therapy are also covered.

PMID- 15561688
TI  - Atypical cellular disorders.
AB  - Some immunologic diseases are characterized by profound loss or primary
      dysfunction of a given population of cells. The atypical cellular disorders
      discussed here all bear some similarities in that abnormal proliferations of
      lymphocytes and macrophages or dendritic cells result in lymphadenopathy, skin
      rashes, bone lesions and infiltrations of nearly any other organ system. What are
      the similarities and the differences between Langerhans cell histiocytosis (LCH),
      sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease,
      and Castleman's disease (CD)? Studies on LCH have some advantages since it was
      described before the others, and organized clinical trials have been done since
      the 1980s. The understanding of SHML benefited from a registry maintained by Drs.
      Rosai and Dorfman. CD was described fifty years ago and for one subtype has the
      most clearly defined etiology (HHV-8 infection) of the three atypical cellular
      disorders discussed here. In Section I, Dr. Kenneth McClain examines the
      unanswered question of whether LCH is a malignant clonal disorder or an
      inflammatory response triggered by aberrant cytokine expression or a virus.
      Advocates of the malignant proliferation theory rest their case primarily on the
      following two points: Clonality of the CD1a+ Langerhans cells was demonstrated by
      analysis of the human androgen receptor in patients with single bone lesions (Low
      Risk) or multisystem disease including spleen, liver, bone marrow, or lung (High
      Risk). Although no consistent chromosomal abnormalities have been reported, loss
      of heterozygosity (LOH) has been defined by comparative genomic hybridization.
      Those in the "inflammatory response" camp note that non-clonal proliferation of
      Langerhans cells in adult pulmonary LCH also have LOH by the same method. The
      pathologic cells have not been successfully grown in culture or immune-deficient
      mice and don't have a "malignant" morphology. While the basic scientific
      arguments continue, important advances in the treatment of LCH have been made by
      international collaborations of the Histiocyte Society. Risk groups have been
      clearly defined and the response to therapy after the initial 6 weeks is known to
      be the strongest prognostic variable for outcome. In Section II, Dr. Yasodha
      Natkunam reviews the features of SHML, which most often presents as painless
      cervical lymphadenopathy, although many patients can have extranodal involvement
      as well. These sites include the skin, respiratory tract, bone, lung,
      gastrointestinal tract, and brain. The diagnosis rests on finding intact
      lymphocytes in the cytoplasm of activated macrophages as well as accumulation of
      mature plasma cells. Hemolytic or non-hemolytic anemias, hypergammaglobulinemia,
      and elevated erythrocyte sedimentatin rate (ESR) are often found with SHML. An
      intriguing finding of human herpesvirus (HHV)-6 viral proteins in SHML has been
      reported in several patients, but needs further study. SHML associated with
      lymphoproliferations triggered by defects in apoptosis are discussed since this
      mechanism may provide a clue to the etiology. Therapy for SHML varies greatly in
      reported case series. Many patients have spontaneous regression or resolution
      after surgical removal of isolated node groups. Others with systemic involvement
      may benefit from chemotherapy, but no clinical trials have been done. In Section
      III, Dr. Steven Swerdlow clarifies key features of the four types of CD.
      Localized cases are divided into the hyaline vascular type and plasma cell type.
      Both are usually cured by surgical excision and have symptoms mainly of a mass
      lesion, although the latter often also has constitutional symptoms. The two types
      are distinguished largely by the nature of the follicles and the number of
      interfollicular plasma cells. Interleukin (IL)-6 expression is increased in the
      plasma cell type. Multicentric CD of the plasmablastic type is most often found
      in HIV-positive patients with coincident HHV-8 infection. Many have lymphomas or
      Kaposi sarcomas. Other cases of multicentric CD are also most like the plasma
      cell type, however, with disseminated disease and constitutional symptoms. A wide
      variety of anti-neoplastic drugs, radiation therapy, anti-IL-6 and rituximab or
      atlizumab have been used with varying success in patients with multicentric CD.
      Clinical trials are needed for SHML and CD and registration of adult and
      pediatric patients on current LCH trials are encouraged.

PMID- 15561689
TI  - Myelodysplastic syndromes.
AB  - The development of new therapeutic strategies for myelodysplastic syndromes (MDS)
      has gained new momentum fueled by improved characterization of the disease's
      natural history and biology and by the recent US Food and Drug Administration
      (FDA) approval of the first agent with an indication for MDS. By integrating
      morphologic and cytogenetic features with greater discriminatory power, the World
      Health Organization (WHO) has refined the classification of these stem cell
      malignancies and enhanced its prognostic utility. Recognition that the malignant
      phenotype, which characterizes MDS, may arise from mechanistically diverse
      biological processes has raised new awareness that treatment strategies must be
      tailored to the pathobiology of the disease. Therapeutics targeting chromatin
      structure, angiogenesis and the microenvironment that nurtures the MDS phenotype
      have demonstrated remarkable activity and offer an opportunity to alter the
      natural history of the disease. This chapter provides an overview of recent
      developments in the characterization of MDS from the microscope to the laboratory
      and the translation of these findings into promising therapeutics. In Section I,
      Dr. James Vardiman reviews the cytogenetic abnormalities that characterize MDS,
      their clinical and pathologic significance, and the application of the WHO
      classification. In Section II, Dr. Alan List reviews treatment goals driven by
      prognostic variables and biological features of the disease that have led to
      promising small molecule, selective therapeutics. In Section III, Dr. Jean-Pierre
      Issa provides an overview of epigenetic events regulating gene expression, which
      may be exploited therapeutically by chromatin remodeling agents. In Section IV,
      Dr. Theo DeWitte discusses new developments in hematopoietic stem cell
      transplantation, including reduced-intensity and myeloablative approaches.

PMID- 15561690
TI  - Marrow failure.
AB  - New discoveries in cell biology, molecular biology and genetics have unveiled
      some of the pathophysiological mysteries of some of the bone marrow failure
      syndromes. Many of these discoveries have revealed why these syndromes show so
      much clinical overlap and some hold the potential for influencing the development
      of new therapies. In children and adults with pancytopenia and hypoplastic bone
      marrows proper differential diagnosis requires that some attention be directed
      toward defining molecular and cellular pathogenetic mechanisms because, once
      identified, some of these mechanisms will clearly suggest rational therapeutic
      approaches, treatment options that should be avoided, or both. In Section I, Drs.
      Jeffrey Lipton and Grover Bagby review the approach to diagnosis and management
      of patients with the inherited bone marrow failure syndromes, Fanconi anemia,
      dyskeratosis congenita, Diamond-Blackfan anemia, and the Shwachman-Diamond
      syndrome. Extraordinary progress has been made in identifying the genes bearing
      pathogenetically relevant mutations in these disorders, but slower progress has
      been made in defining the precise functions of the proteins these genes encode in
      normal cells, in part because it is increasingly obvious that the proteins are
      multifunctional. In practice, it is clear that in patients with dyskeratosis
      congenita and Fanconi anemia, the diagnosis must be considered not only in
      children but in adults as well. In Section II, Dr. Elaine Sloand outlines a very
      practical and evidence-based approach to diagnosis and management of acquired
      hypoplastic states emphasizing overlap between non-clonal and clonal
      hematopoiesis is such conditions. The pathogenesis of T lymphocyte-mediated
      marrow failure is presented as a clear-cut rationale for use of immunosuppressive
      therapy and stem cell transplantation. Practical management of patients with
      refractory disease with and without evidence of clonal evolution (either
      paroxysmal nocturnal hemoglobinuria [PNH] or myelodysplasia [MDS]) is presented.
      In Section III, the challenge of hypoplastic MDS is reviewed by Dr. Charles
      Schiffer. After reviewing the most up-to-date classification scheme, therapeutic
      options are reviewed, focusing largely on agents that have most recently shown
      some promising activity, including DNA demethylating agents, thalidomide and
      CC5013, arsenic trioxide, and immunosuppressive therapy. Here are also outlined
      the rationale and the indications for choosing allogeneic bone marrow
      transplantation, the only therapy with known curative potential.

PMID- 15561691
TI  - Immunotherapeutic approaches for hematologic malignancies.
AB  - The immune system has two complementary arms: one is older and seemingly more
      primitive, called the innate immune system, found in both plants and animals. The
      second (already many millions of years old!) is the adaptive or antigen-specific
      immune system, limited to vertebrate animals. The human innate immune system has
      many cellular elements that include granulocytes, monocytes, macrophages, natural
      killer (NK) cells, mast cells, eosinophils, and basophils. Receptors for these
      cells are non-clonal, fixed in the genome, requiring no rearrangement, and
      recognize conserved molecular patterns that are specific to pathogens. The
      adaptive immune system (B cells and T cells) have receptors with great variation,
      able to recognize an almost an unlimited number of highly specific pathogens
      through rearrangement of receptor gene segments, and can also provide
      immunological memory so critical for vaccination. As the immune system has
      evolved to recognize non-self, malignant transformation of self can likely escape
      immune surveillance with relative ease. Contributors to this chapter are
      utilizing distinct components of either the innate or adaptive immune system that
      recognize non-self, in combination with what we know about differences between
      malignant and normal self, in an effort to develop novel and effective
      immunologic approaches against hematologic malignancies. In Section I, Dr. Andrea
      Velardi reviews the benefits of NK cell alloreactivity in mismatched
      hematopoietic transplantation, provides updates on current clinical trials, and
      discusses further therapeutic perspectives emerging from murine bone marrow
      transplant models. In Section II, Dr. David Scheinberg reviews novel leukemic
      antigens being targeted by humanized monoclonal antibodies as well as mechanisms
      by which antibody-mediated cytotoxicity occurs in vivo. In Section III, Dr. Ivan
      Borrello reviews vaccine and adoptive T cell immunotherapy in the treatment of
      hematologic malignancies. Specifically, he discusses the various vaccine
      approaches used as well as strategies aimed at augmenting the tumor specificity
      of T cell therapies.

PMID- 15561692
TI  - Stem cell transplantation (cord blood transplants).
AB  - Allogeneic stem cell transplantation is an accepted treatment modality for
      selected malignant and non-malignant diseases. However, the ability to identify
      suitably matched related or unrelated donors can be difficult in some patients.
      Alternative sources of stem cells such as cord blood provide a readily available
      graft for such patients. Data accumulated over the past several years have
      demonstrated that the use of cord blood is an accepted source of stem cells for
      pediatric patients. Since the cell numbers of hematopoietic progenitors in cord
      blood is limited and the collection can occur only in a single occasion, its use
      in adult patients can be more problematic. Here, new developments in the use of
      cord blood for adults and studies aimed at expansion of cord blood cells and
      immune reconstitution are described. In Section I, Dr. Nelson Chao describes the
      early data in cord blood transplantation in adult patients. The patient outcomes
      are reviewed and analyzed for various factors such as cell dose, HLA typing, and
      patient selection that could have contributed to the final outcome of these adult
      patients. Myeloablative as well as nonmyeloablative approaches are presented.
      Discussion of the various benefits and risks are presented. More recent data from
      multiple single institutions as well as larger registry data comparisons are also
      provided. Analyses of these studies suggest methods to improve on the outcome.
      These newer data should lead to a logical progression in the use of cord blood
      cells in adult patients. In Section II, Dr. Stephen Emerson describes the
      historical efforts associated with expansion of hematopoietic stem cells,
      specifically with cord blood cells. These efforts to expand cord blood cells
      continue with novel methods. Moreover, a better understanding of stem cell
      biology and signaling is critical if we are to be able to effectively expand
      these cells for clinical use. An alternative, more direct, approach to expanding
      stem cells could be achieved by specific genetic pathways known or believed to
      support primitive HSC proliferation such as Notch-1 receptor activation, Wnt/LEF
      1 pathway induction, telomerase or the Homeobox (Hox) gene products. The clinical
      experience with the use of expanded cord blood cells is also discussed. In
      Section III, Dr. Kenneth Weinberg describes immune reconstitution or lack thereof
      following cord blood transplantation. One of the hallmarks of successful
      hematopoietic stem cell transplantation is the ability to fully reconstitute the
      immune system of the recipient. Thus, the relationship between stem cell source
      and the development of T lymphocyte functions required for protection of the
      recipient from infection will be described, and cord blood recipients will be
      compared with those receiving other sources of stem cells. T cell development is
      described in detail, tracking from prethymic to postthymic lymphocytes with
      specific attention to umbilical cord blood as the source of stem cells. Moreover,
      a discussion of the placenta as a special microenvironment for umbilical cord
      blood is presented. Strategies to overcome the immunological defects are
      presented to improve the outcome of these recipients.

PMID- 15561693
TI  - Supportive care.
AB  - To optimize treatment outcomes for hematologic malignancies, minimizing the
      consequences of treatment complications requires as much skill as the choice of
      the treatment itself. Myelosuppression and immunosuppression are frequent
      complications and have potentially serious infectious consequences. Invasive
      fungal infections and infections from respiratory viruses are increasing in
      frequency and have life-threatening potential. Damage to vital organs, especially
      the liver, is another important concern. In this chapter, the scope of invasive
      fungal and respiratory viral infections, recent insights into the pathogenesis of
      hepatic sinusoidal injury, and recent developments that impact prevention and
      treatment approaches for these complications are described. In Section I, Dr.
      John Wingard describes the advantages and disadvantages of various treatment
      options for invasive infections by the two chief fungal pathogens, Candida and
      Aspergillus. Adjunctive therapies and practical considerations that clinicians
      should weigh in choosing one or another of the various agents are discussed. The
      studies that have evaluated antifungal prophylaxis and empirical treatment
      strategies are reviewed. Finally, new approaches such as combination therapy, new
      diagnostics, and efforts to bolster host immunity are considered. In Section II,
      Dr. W. Garrett Nichols describes the epidemiology of community-acquired
      respiratory viruses (CRV) in patients with hematologic malignancies. Risk
      factors, clinical syndromes, and possible indirect effects of CRV infections are
      discussed. Treatment and prevention options are reviewed. In Section III, Dr.
      George McDonald describes sinusoidal obstruction syndrome (once known as hepatic
      veno-occlusive disease). Recent insights into pathogenesis are described.
      Diagnostic criteria and the advantages and disadvantages of various diagnostic
      methods are reviewed and prognosis is considered. Prevention and treatment
      options are discussed.

PMID- 15561694
TI  - Congenital and acquired thrombocytopenia.
AB  - The diagnosis and management of thrombocytopenia is a growing component in the
      practice of hematology. The frequency with which hematologists are called in
      consultation for thrombocytopenia continues to increase with the advent of
      routine automated platelet determinations and the introduction of new
      medications. For most patients, such as those with inherited and auto-immune
      thrombocytopenia, emphasis is focused on efforts to treat or forestall bleeding
      without excess drug-induced toxicity or burden to the patient. However, in
      disorders such as heparin-induced thrombocytopenia (HIT), avoidance of thrombotic
      complications is the key to management. In this chapter, we provide the pediatric
      and adult hematologist with new insights into the pathogenesis and recognition of
      congenital inherited thrombocytopenias (CTP), a hitherto difficult to comprehend
      constellation of clinical entities. We also highlight new approaches to the
      diagnosis and treatment of two of the more common thrombocytopenic conditions
      encountered in practice, autoimmune or idiopathic thrombocytopenic purpura (ITP)
      and HIT. In Section I, Dr. James Bussel discusses CTPs and their distinction from
      childhood ITP. He emphasizes the clinical features that enable the pediatrician
      and hematologist to suspect the diagnosis of CTP and those that are of use to
      subcategorize the various entities, where possible. He also emphasizes newer
      molecular markers that afford definitive diagnosis in some cases and provide
      insight into platelet production. This section highlights the characteristic
      associated findings and differences in the natural history and approaches to
      management of the various entities. In Section II, Dr. Robert McMillan discusses
      adult chronic ITP. He revisits the utility of platelet antibody determination in
      diagnosis and review new insights into pathogenesis. The role of Helicobacter
      pylori infection and the timing of splenectomy in the management of acute and
      emergent ITP are examined. New insights into the natural history of ITP post
      splenectomy and management strategies for patients with severe, chronic,
      refractory ITP are discussed. In Section III, Dr. James Zehnder updates us on
      HIT. He emphasizes new insights into the clinical presentation and pathogenesis
      of this condition. He critically reviews the utility of laboratory testing for
      heparin-dependent antibodies. Recent studies on the use of direct thrombin
      inhibitors are examined and the management of cardiopulmonary bypass surgery in
      patients with HIT is discussed.

PMID- 15561695
TI  - Recent advances in thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic
      hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis
      that causes variable degrees of tissue ischemia and infarction. Intravascular
      coagulation is not a prominent feature of the disorder. Plasma exchange can
      induce remissions in approximately 80% of patients with idiopathic TTP, but
      patients have a much worse prognosis when thrombotic microangiopathy is
      associated with cancer, certain drugs, infections, or tissue transplantation.
      Recently, acquired autoimmune deficiency of a plasma metalloprotease named
      ADAMTS13 was shown to cause many cases of idiopathic TTP. This review describes
      our current understanding of how to use this knowledge clinically. In Section I,
      Dr. Joel Moake describes the presentation of thrombotic microangiopathy,
      emphasizing the pathophysiology of idiopathic TTP. Platelets adhere to ultra
      large (or "unusually large") von Willebrand factor (ULVWF) multimers that are
      immobilized in exposed subendothelial connective tissue and secreted into the
      circulation in long "strings" from stimulated endothelial cells. ADAMTS13 cleaves
      ULVWF multimers within growing platelet aggregates under flowing conditions, and
      this normally limits platelet thrombus formation. If ADAMTS13 is absent, either
      congenitally or due to acquired autoantibodies, platelet-rich microvascular
      thrombosis proceeds unchecked and TTP ensues. Plasma exchange is effective
      therapy for idiopathic TTP, probably because it replenishes the deficient
      ADAMTS13 and removes some of the pathogenic autoantibodies and endothelial
      stimulating cytokines. Some patients have a type of thrombotic microangiopathy
      after transplantation/chemotherapy but do not have severe ADAMTS13 deficiency.
      The pathogenesis of their disease must differ but remains poorly understood. In
      Section II, Dr. Toshiyuki Miyata describes recent advances in assay methods that
      should facilitate routine laboratory testing of ADAMTS13 for patients with
      thrombotic microangiopathy. ADAMTS13 cleaves a single Tyr-Met bond in domain A2
      of the VWF subunit. ADAMTS13 assays based on the cleavage of plasma VWF multimers
      have been used extensively but require considerable time and expertise to
      perform. A recombinant substrate containing 73 amino acid residues of VWF domain
      A2 has been devised that allows short incubation times and rapid product
      detection by gel electrophoresis or immunoassay. These results should encourage
      the development of even simpler assays that can be performed in most clinical
      laboratories. In Section III, Dr. James George provides an update on the long
      term prospective study of thrombotic microangiopathy in the Oklahoma TTP-HUS
      Registry. At presentation, the clinical distinction between idiopathic TTP,
      various forms of secondary thrombotic microangiopathy, and even Shiga toxin
      associated hemolytic uremic syndrome (HUS) can be problematic because the
      symptoms and laboratory findings often overlap. Consequently, plasma exchange
      usually is administered to any patient with thrombotic microangiopathy if there
      is doubt about the cause. The role of ADAMTS13 testing in choosing therapy
      remains uncertain, but the results do appear to have prognostic significance.
      Severe ADAMTS13 deficiency is specific for idiopathic TTP and identifies a
      subgroup with a high likelihood of response to plasma exchange, and high-titer
      ADAMTS13 inhibitors correlate strongly with a high risk of relapsing disease.
      Patients with normal ADAMTS13 activity have a much worse prognosis, although many
      factors probably contribute to this difference. Longitudinal study of these
      patients will continue to clarify the relationship of ADAMTS13 deficiency to the
      clinical course of thrombotic microangiopathy.

PMID- 15561696
TI  - Thrombophilia and new anticoagulant drugs.
AB  - Venous thromboembolism, which includes deep vein thrombosis and pulmonary
      embolism, is the result of an imbalance among procoagulant, anticoagulant and
      profibrinolytic processes. This imbalance reflects a complex interplay between
      genetic and environmental or acquired risk factors. Genetic thrombophilic defects
      influence the risk of a first episode of thrombosis. How these defects influence
      the risk of recurrence in patients whose first episode of venous thromboembolism
      was unprovoked is less certain. Thus, when anticoagulants are stopped, patients
      with unprovoked venous thromboembolism have a risk of recurrence of at least 7%
      to 10% per year, even in the absence of an underlying thrombophilic defect.
      Consequently, there is a trend toward longer durations of anticoagulation therapy
      for these patients, which is problematic given the limitation of existing
      anticoagulants. This chapter provides an overview of the thrombophilic defects
      and how they influence the risk of venous thromboembolism. The chapter also
      details advances in anticoagulant therapy, focusing on new inhibitors of factor
      Xa and thrombin. In Section I, Dr. Saskia Middeldorp describes the various
      thrombophilic defects and reviews their relative importance in the pathogenesis
      of a first episode of venous thromboembolism. She then discusses the influence of
      these defects on the risk of recurrent thrombotic events in patients with
      unprovoked venous thromboembolism and in those whose thrombosis occurred in
      association with a known risk factor, such as surgery. In Section II, Dr. William
      Geerts reviews the pharmacology of new parenteral and oral factor Xa inhibitors
      and describes the results of the Phase II and III clinical trials with these
      agents. He then provides perspective on the potential advantages and drawbacks of
      these drugs for the prevention and treatment of venous thromboembolism. In
      Section III, Dr. John Heit focuses on direct thrombin inhibitors. He discusses
      their mechanism of action and compares and contrasts their pharmacological
      profiles prior to describing the results of Phase II and III clinical trials. Dr.
      Heit then provides perspective on the potential advantages and limitations of
      these drugs relative to existing anticoagulants.

PMID- 15561697
TI  - Deep venous thrombosis.
AB  - Venous thromboembolism (VTE), manifested as either deep venous thrombosis (DVT)
      or pulmonary embolism (PE), is an extremely common medical problem, occurring
      either in isolation or as a complication of other diseases or procedures. Yet,
      despite its frequency, much remains to be learned regarding the pathogenic
      mechanisms that initiate VTE, about tailoring its treatment to the individual
      with her/his specific set of risk factors for recurrence, and about its medical
      management when associated with specific disease entities, such as cancer. These
      three topics are addressed in this chapter. In Section I, Drs. Lopez and Conde
      discuss the mechanisms by which venous thrombi may be initiated on the vessel
      wall in the absence of anatomically overt vessel wall injury. The authors propose
      a model whereby tissue factor (TF)-bearing microvesicles that arise from cells of
      monocyte/macrophage lineage can fuse with activated endothelial cells in regions
      of vessel activation or inflammation and initiate blood coagulation. Key
      components of this model include docking of the microvesicles to the stimulated
      endothelium through P-selectin glycoprotein ligand-1 on their surfaces binding to
      either P-selectin or E-selectin on the endothelium, and the role of hypoxia
      during blood stasis in initiating local endothelial activation. Elevations in the
      levels of TF-bearing microvesicles associated with inflammatory conditions would
      help to explain the increased risk of thrombosis associated with infections and
      inflammatory states such as inflammatory bowel disease. In Section II, Dr. Clive
      Kearon discusses the risk factors for recurrent thrombosis and strategies for
      determining length of therapy and tailoring specific therapies through risk
      stratification. Those patients who experience VTE in association with a major
      reversible risk factor such as surgery are much less likely to experience a
      recurrence when anticoagulation is discontinued than are patients with a
      persistent risk factor, such as thrombophilia or cancer unresponsive to therapy.
      Those with a minor reversible risk factor, such as prolonged air travel, have an
      intermediate risk of recurrence after discontinuance of anticoagulant therapy.
      The author provides an algorithm for using risk assessment as a means of
      determining the length and type of therapy to be used to minimize the rate of
      recurrence while simultaneously diminishing the risk of bleeding associated with
      anticoagulation. In Section III, Dr. Agnes Lee updates the topic of VTE
      associated with malignancy. Patients with cancer make up approximately 20% of
      those presenting with first time VTE, and the presence of VTE forebodes a much
      poorer prognosis for patients with cancer, likely because of the morbidity
      associated with VTE itself and because VTE may herald a more aggressive cancer.
      Recent evidence indicates that low-molecular weight heparins (LMWHs) improve
      survival in patients with advanced cancer through mechanisms beyond their effect
      as anticoagulants. Because of their improved efficacy and safety and potential
      anti-neoplastic effect, the LMWHs have become the anticoagulants of choice for
      treating VTE associated with cancer.

PMID- 15561698
TI  - Joint ASH and AABB educational session.
AB  - In the vein-to-vein flow of blood from donor to patient, the role of the
      transfusion medicine specialist has become increasingly centered at the bedside.
      Three clinically centered issues in blood safety and in blood conservation are
      presented in this chapter. In Section I, Dr. Patricia Hewitt presents the
      epidemiologic and clinical evidence regarding new variant Creutzfeldt-Jakob
      disease (nvCJD) in the UK and its relevance to transfusion medicine. Lessons
      learned from the responses by the National Blood Service to this crisis are
      discussed, particularly in the context of recent evidence of a case of vCJD
      transmission by blood transfusion and a second case of apparent transmission of
      abnormal prion protein without development of clinical illness. In Section II,
      Dr. Christopher Silliman and his colleagues summarize recent knowledge gained
      regarding transfusion-related acute lung injury (TRALI), which is now the leading
      cause of transfusion-related mortality. Two different etiologies have been
      proposed: a single antibody-medicated event, involving anti-HLA Class I and Class
      II, or anti-granulocyte antibodies; and a two-event model, which includes the
      clinical condition of the patient resulting in pulmonary endothelial activation
      and neutrophil sequestration. The second event is the transfusion of a biologic
      response modifier (lipids or antibodies) in the blood component that activates
      primed neutrophils. Prevention, clinical treatment, and proposed definition of
      TRALI are discussed. In Section III, Dr. Lawrence Goodnough and colleagues
      present a transfusion medicine service approach to the utilization of recombinant
      factor VIIa (rFVIIa) in non-approved clinical settings. rFVIIa has a potential
      role as a hemostatic intervention in a variety of clinical settings, yet few
      clinical trials have been completed to date to guide indications for its use. The
      policies presented here are those in place at the authors' medical center, and
      will undergo periodic review and revision as relevant new information and data
      are generated.

PMID- 15561699
TI  - Hematology grants workshop.
AB  - Obtaining research funding is of utmost importance for academic hematologists,
      especially those engaged in basic science research. Several funding mechanisms
      are available to researchers working in the fields of Hematology and/or Oncology.
      This chapter will discuss various issues relating to applications for National
      Institutes of Health (NIH) R01 grants, the classic funding mechanism for
      investigator-initiated research. It will also discuss other opportunities for
      funding from other government agencies, including the Department of Veterans
      Affairs and the Department of Defense. We will also provide a summary of the
      process by which NIH R01 applications are reviewed and some guidelines and tips
      for the successful writing of R01 grants or their equivalents from other
      agencies.

PMID- 15561700
TI  - Characterizing the sphingolipid signaling pathway that remediates defects
      associated with loss of the yeast amphiphysin-like orthologs, Rvs161p and
      Rvs167p.
AB  - Loss of function of either the RVS161 or RVS167 Saccharomyces cerevisiae
      amphiphysin-like gene confers similar growth phenotypes that can be suppressed by
      mutations in sphingolipid biosynthesis. We performed a yeast two-hybrid screen
      using Rvs161p as bait to uncover proteins involved in this sphingolipid-dependent
      suppressor pathway. In the process, we have demonstrated a direct physical
      interaction between Rvs167p and the two-hybrid interacting proteins, Acf2p,
      Gdh3p, and Ybr108wp, while also elucidating the Rvs167p amino acid domains to
      which these proteins bind. By using subcellular fractionation, we demonstrate
      that Rvs167p, Ybr108wp, Gdh3p, and Acf2p all localize to Rvs161p-containing lipid
      rafts, thus placing them within a single compartment that should facilitate their
      interactions. Moreover, our results suggest that Acf2p and Gdh3p functions are
      needed for suppressor pathway activity. To determine pathway mechanisms further,
      we examined the localization of Rvs167p in suppressor mutants. These studies
      reveal roles for Rvs161p and the very long chain fatty acid elongase, Sur4p, in
      the localization and/or stability of Rvs167p. Previous yeast studies showed that
      rvs defects could be suppressed by changes in sphingolipid metabolism brought
      about by deleting SUR4 (Desfarges, L., Durrens, P., Juguelin, H., Cassagne, C.,
      Bonneu, M., and Aigle, M. (1993) Yeast 9, 267-277). Using rvs167 sur4 and rvs161
      sur4 double null cells as models to study suppressor pathway activity, we
      demonstrate that loss of SUR4 does not remediate the steady-state actin
      cytoskeletal defects of rvs167 or rvs161 cells. Moreover, suppressor activity
      does not require the function of the actin-binding protein, Abp1p, or Sla1p, a
      protein that is thought to regulate assembly of the cortical actin cytoskeleton.
      Based on our results, we suggest that sphingolipid-dependent suppression of rvs
      defects may not work entirely through regulating changes in actin organization.

PMID- 15561701
TI  - Novel function of androgen receptor-associated protein 55/Hic-5 as a negative
      regulator of Smad3 signaling.
AB  - Androgen receptor-associated protein 55 (ARA55/Hic-5) belongs to the LIM protein
      superfamily and is featured by three or four N-terminal LD motifs and four C
      terminal zinc finger-like LIM domains. Both LD motifs and LIM domains can serve
      as protein-protein interaction interfaces. Recently, we found that enforced
      expression of ARA55 inhibits transforming growth factor-beta-mediated up
      regulation of Smad binding element-luciferase reporter activity in NRP-154 and
      NRP-152 rat prostate and LNCaP human prostate cell lines. Moreover, ARA55 also
      inhibits the induction of Smad-binding element 4-luciferase and 3TP-luciferase (a
      plasminogen activator inhibitor-1 (PAI-1) promoter construct) reporters by
      constitutively active (CA)-Smad3 in these cell lines. Co-immunoprecipitation
      studies suggest an interaction between ARA55 and either CA-Smad3 or wild-type
      Smad3 in HEK293 cells that occurs through the MH2 domain of Smad3 and the C
      terminus of ARA55 with wild-type Smad3 having stronger affinity than CA-Smad3 to
      ARA55. Glutathione S-transferase pull-down assays demonstrate that this
      interaction can occur in a cell-free system. These results are consistent with
      the luciferase data showing that the C terminus of ARA55 is critical for
      suppression of Smad3 activity. Furthermore, using a mammalian two-hybrid system,
      we confirmed that ARA55 interacts with the MH2 domain of Smad3 and suppresses CA
      Smad3-induced transcriptional responses. In conclusion, these results support
      that ARA55 selectively intercepts transforming growth factor-beta signaling
      through an interaction of the LIM domain of ARA55 with the MH2 domain of Smad3.

PMID- 15561702
TI  - Nitric oxide inhibition of homocysteine-induced human endothelial cell apoptosis
      by down-regulation of p53-dependent Noxa expression through the formation of S
      nitrosohomocysteine.
AB  - Hyperhomocysteinemia is believed to induce endothelial dysfunction and promote
      atherosclerosis; however, the pathogenic mechanism has not been clearly
      elucidated. In this study, we examined the molecular mechanism by which
      homocysteine (HCy) causes endothelial cell apoptosis and by which nitric oxide
      (NO) affects HCy-induced apoptosis. Our data demonstrated that HCy caused caspase
      dependent apoptosis in cultured human umbilical vein endothelial cells, as
      determined by cell viability, nuclear condensation, and caspase-3 activation and
      activity. These apoptotic characteristics were correlated with reactive oxygen
      species (ROS) production, lipid peroxidation, p53 and Noxa expression, and
      mitochondrial cytochrome c release following HCy treatment. HCy also induced p53
      and Noxa expression and apoptosis in endothelial cells from wild type mice but
      not in the p53-deficient cells. The NO donor S-nitroso-N-acetylpenicillamine,
      adenoviral transfer of inducible NO synthase gene, and antioxidants (alpha
      tocopherol and superoxide dismutase plus catalase) but not oxidized SNAP, 8-Br
      cGMP, nitrite, and nitrate, suppressed ROS production, p53-dependent Noxa
      expression, and apoptosis induced by HCy. The cytotoxic effect of HCy was
      decreased by small interfering RNA-mediated suppression of Noxa expression,
      indicating that Noxa up-regulation plays an important role in HCy-induced
      endothelial cell apoptosis. Overexpression of inducible NO synthase increased the
      formation of S-nitroso-HCy, which was inhibited by the NO synthase inhibitor N
      monomethyl-l-arginine. Moreover, S-nitroso-HCy did not increase ROS generation,
      p53-dependent Noxa expression, and apoptosis. These results suggest that up
      regulation of p53-dependent Noxa expression may play an important role in the
      pathogenesis of atherosclerosis induced by HCy and that an increase in vascular
      NO production may prevent HCy-induced endothelial dysfunction by S-nitrosylation.

PMID- 15561703
TI  - A carboxypeptidase inhibitor from the tick Rhipicephalus bursa: isolation, cDNA
      cloning, recombinant expression, and characterization.
AB  - A novel proteinaceous metallo-carboxypeptidase inhibitor, named tick
      carboxypeptidase inhibitor (TCI), was isolated from the ixodid tick Rhipicephalus
      bursa and N-terminally sequenced. The complete cDNA encoding this protein was
      cloned from tick mRNA by reverse transcription-PCR and rapid amplification of
      cDNA ends techniques. The full-length TCI cDNA contains an open reading frame
      coding for a precursor protein of 97 amino acid residues that consists of a
      predicted signal peptide of 22 residues and of mature TCI, a 75-residue cysteine
      rich protein (12 Cys). The deduced amino acid sequence shows no homology to other
      known proteins; the C terminus, however, resembles those of other protein metallo
      carboxypeptidase inhibitors, suggesting a common mechanism of inhibition.
      Recombinant TCI expressed in Escherichia coli is fully functional and inhibits
      carboxypeptidases of the A/B subfamily with equilibrium dissociation constants in
      the nanomolar range. Structural analyses by circular dichroism and nuclear
      magnetic resonance indicate that TCI is a protein strongly constrained by
      disulfide bonds, unusually stable over a wide pH range and highly resistant to
      denaturing conditions. As a tight binding inhibitor of plasma carboxypeptidase B,
      also known as thrombin-activatable fibrinolysis inhibitor, recombinant TCI
      stimulates fibrinolysis in vitro and thus may have potential for applications to
      prevent or treat thrombotic disorders.

PMID- 15561704
TI  - Phosphorylation-independent beta-arrestin translocation and internalization of
      leukotriene B4 receptors.
AB  - Leukotriene B4 (LTB4) activates the G-protein-coupled receptor leukotriene B4
      receptor 1 (BLT1) to mediate a diverse array of cellular responses in leukocytes
      including chemotaxis, calcium mobilization, degranulation, and gene expression.
      To determine the role of phosphorylation in BLT1 regulation, we generated mutants
      of BLT1 in which all of the serine/threonine residues in the C-tail are converted
      to alanine or to aspartate/glutamate. These mutants expressed in rat basophilic
      leukemia RBL-2H3 cells bound LTB4 with similar affinity and activated all of the
      known functional activities of BLT1, albeit at different levels. The conversion
      of phosphorylation sites to alanine resulted in enhanced G-protein-mediated
      activities, whereas conversion to aspartate/glutamate resulted in reduced
      responses and a right shift in dose response, indicating that receptor
      phosphorylation is a critical regulator of G-protein-mediated pathways.
      Surprisingly, translocation of beta-arrestin and receptor internalization was
      completely independent of BLT1 phosphorylation. Real-time analysis of beta
      arrestin translocation and receptor internalization using digital fluorescence
      video microscopy in cells expressing a red fluorescent protein labeled BLT1 and a
      green fluorescent protein-tagged beta-arrestin confirmed phosphorylation
      independent beta-arrestin translocation and internalization of BLT1. In beta
      arrestin-deficient mouse embryo fibroblasts, the BLT1 receptors failed to display
      endosomal localization upon stimulation. In these cells, co-expression of beta
      arrestin-green fluorescent protein with BLT1-red fluorescent protein resulted in
      co-localization of BLT1 and beta-arrestin upon activation. Thus, receptor
      phosphorylation-dependent mechanisms regulate G-protein-mediated pathways;
      however, phosphorylation-independent mechanisms regulate beta-arrestin
      association and internalization of BLT1.

PMID- 15561705
TI  - Post-translational amino acid isomerization: a functionally important D-amino
      acid in an excitatory peptide.
AB  - The post-translational modification of an L- to a D-amino acid has been
      documented in relatively few gene products, mostly in small peptides under 10
      amino acids in length. In this report, we demonstrate that a 46-amino acid
      polypeptide toxin has one D-phenylalanine at position 44, and that the
      epimerization from an L-Phe to a D-Phe has a dramatic effect on the excitatory
      effects of the peptide. In one electrophysiological assay carried out, the D-Phe
      containing peptide was extremely potent, whereas the unmodified polypeptide had
      no biological activity, demonstrating that the chirality of the post
      translationally modified amino acid is functionally significant. The peptide
      toxin analyzed, r11a, belongs to the I-gene superfamily of conotoxins that has
      four disulfide cross-links. The D-Phe in r11a is at the third amino acid from the
      C terminus, the same relative position from the C-terminal end as the d-amino
      acid in omega-agatoxin TK from a spider, an unrelated peptide. Thus, although
      post-translational amino acid isomerization appears to have no strong specificity
      for the chemical nature of the amino acid side chain, the few peptides where this
      modification has been established suggest that there may be favored positions
      near the N or C terminus that are preferential sites for isomerization to a D
      amino acid.

PMID- 15561706
TI  - DNA polymerase beta and flap endonuclease 1 enzymatic specificities sustain DNA
      synthesis for long patch base excision repair.
AB  - DNA polymerase beta (pol beta) and flap endonuclease 1 (FEN1) are key players in
      pol beta-mediated long-patch base excision repair (LP-BER). It was proposed that
      this type of LP-BER is accomplished through FEN1 removal of a 2- to 11-nucleotide
      flap created by pol beta strand displacement DNA synthesis. To understand how
      these enzymes might cooperate during LP-BER, we characterized purified human pol
      beta DNA synthesis by utilizing various BER intermediates, including single
      nucleotide-gapped DNA, nicked DNA, and nicked DNA with various lengths of flaps
      all with a 5'-terminal tetrahydrofuran (THF) residue. We observed that nicked DNA
      and nicked-THF flap DNA were poor substrates for pol beta-mediated DNA synthesis;
      yet, DNA synthesis was strongly stimulated by purified human FEN1. FEN1 did not
      improve pol beta substrate binding. FEN1 cleavage activity was required for the
      stimulation, suggesting that FEN1 removed a barrier to pol beta DNA synthesis. In
      addition, FEN1 cleavage on both nicked and nicked-THF flap DNA resulted in a one
      nucleotide gapped DNA molecule that was an ideal substrate for pol beta. This
      study demonstrates that pol beta cooperates with FEN1 to remove DNA damage via a
      "Hit and Run" mechanism, involving alternating short gap production by FEN1 and
      gap filling by pol beta, rather than through coordinated formation and removal of
      a strand-displaced flap.

PMID- 15561707
TI  - Molecular characterization, expression, and in vivo analysis of LmexCht1: the
      chitinase of the human pathogen, Leishmania mexicana.
AB  - Chitinases have been implicated to be of importance in the life cycle development
      and transmission of a variety of parasitic organisms. Using a molecular approach,
      we identified and characterized the structure of a single copy LmexCht1-chitinase
      gene from the primitive trypanosomatid pathogen of humans, Leishmania mexicana.
      The LmexCht1 encodes an approximately 50 kDa protein, with well conserved
      substrate binding and catalytic domains characteristic of members of the
      chitinase-18 protein family. Further, we showed that LmexCht1 mRNA is
      constitutively expressed by both the insect vector (i.e. promastigote) and
      mammalian (i.e. amastigote) life cycle developmental forms of this protozoan
      parasite. Interestingly, however, amastigotes were found to secrete/release
      approximately >2-4-fold higher levels of chitinase activity during their growth
      in vitro than promastigotes. Moreover, a homologous episomal expression system
      was devised and used to express an epitope-tagged LmexCht1 chimeric construct in
      these parasites. Expression of the LmexCht1 chimera was verified in these
      transfectants by reverse transcription-PCR, Western blots, and indirect
      immunofluorescence analyses. Further, results of coupled
      immunoprecipitation/enzyme activity experiments demonstrated that the LmexCht1
      chimeric protein was secreted/released by these transfected L. mexicana parasites
      and that it possessed functional chitinase enzyme activity. Such transfectants
      were also evaluated for their infectivity both in human macrophages in vitro and
      in two different strains of mice. Results of those experiments demonstrated that
      the LmexCht1 transfectants survived significantly better in human macrophages and
      also produced significantly larger lesions in mice than control parasites. Taken
      together, our results indicate that the LmexCht1-chimera afforded a definitive
      survival advantage to the parasite within these mammalian hosts. Thus, the
      LmexCht1 could potentially represent a new virulence determinant in the mammalian
      phase of this important human pathogen.

PMID- 15561708
TI  - Characterization of the NifS-like domain of ABA3 from Arabidopsis thaliana
      provides insight into the mechanism of molybdenum cofactor sulfuration.
AB  - The molybdenum cofactor sulfurase ABA3 from Arabidopsis thaliana specifically
      regulates the activity of the molybdenum enzymes aldehyde oxidase and xanthine
      dehydrogenase by converting their molybdenum cofactor from the desulfo-form into
      the sulfo-form. ABA3 is a two-domain protein with an NH2-terminal domain sharing
      significant similarities to NifS proteins that catalyze the decomposition of l
      cysteine to l-alanine and elemental sulfur for iron-sulfur cluster synthesis.
      Although different in its physiological function, the mechanism of ABA3 for
      sulfur mobilization was found to be similar to NifS proteins. The protein binds a
      pyridoxal phosphate cofactor and a substrate-derived persulfide intermediate, and
      site-directed mutagenesis of strictly conserved binding sites for the cofactor
      and the persulfide demonstrated that they are essential for molybdenum cofactor
      sulfurase activity. In vitro, the NifS-like domain of ABA3 activates aldehyde
      oxidase and xanthine dehydrogenase in the absence of the C-terminal domain, but
      in vivo, the C-terminal domain is required for proper activation of both target
      enzymes. In addition to its cysteine desulfurase activity, ABA3-NifS also
      exhibits selenocysteine lyase activity. Although l-selenocysteine is unlikely to
      be a natural substrate for ABA3, it is decomposed more efficiently than l
      cysteine. Besides mitochondrial AtNFS1 and plastidial AtNFS2, which are both
      proposed to be involved in iron-sulfur cluster formation, ABA3 is proposed to be
      a third and cytosolic NifS-like cysteine desulfurase in A. thaliana. However, the
      sulfur transferase activity of ABA3 is used for post-translational activation of
      molybdenum enzymes rather than for iron-sulfur cluster assembly.

PMID- 15561709
TI  - A relaxed discrimination of 2'-O-methyl-GTP relative to GTP between de novo and
      Elongative RNA synthesis by the hepatitis C RNA-dependent RNA polymerase NS5B.
AB  - Several nucleotide analogues have been described as inhibitors of NS5B, the
      essential viral RNA-dependent RNA polymerase of hepatitis C virus. However, their
      precise mode of action remains poorly defined at the molecular level, much like
      the different steps of de novo initiation of viral RNA synthesis. Here, we show
      that before elongation, de novo RNA synthesis is made of at least two distinct
      kinetic phases, the creation of the first phosphodiester bond being the most
      efficient nucleotide incorporation event. We have studied 2'-O-methyl-GTP as an
      inhibitor of NS5B-directed RNA synthesis. As a nucleotide competitor of GTP in
      RNA synthesis, 2'-O-methyl-GTP is able to act as a chain terminator and inhibit
      RNA synthesis. Relative to GTP, we find that this analogue is strongly
      discriminated against at the initiation step ( approximately 150-fold) compared
      with approximately 2-fold at the elongation step. Interestingly, discrimination
      of the 2'-O-methyl-GTP at initiation is suppressed in a variant NS5B deleted in a
      subdomain critical for initiation (the "flap," encompassing amino acids 443-454),
      but not in P495L NS5B, which shows a selective alteration of transition from
      initiation to elongation. Our results demonstrate that the conformational change
      occurring between initiation and elongation is dependent on the allosteric GTP
      binding site and relaxes nucleotide selectivity. RNA elongation may represent the
      most probable target of 2'-modified nucleotide analogues, because it is more
      permissive to inhibition than initiation.

PMID- 15561710
TI  - Acceleration of glutathione efflux and inhibition of gamma-glutamyltranspeptidase
      sensitize metastatic B16 melanoma cells to endothelium-induced cytotoxicity.
AB  - Highly metastatic B16 melanoma (B16M)-F10 cells, as compared with the low
      metastatic B16M-F1 line, have higher GSH content and preferentially overexpress
      BCL-2. In addition to its anti-apoptotic properties, BCL-2 inhibits efflux of GSH
      from B16M-F10 cells and thereby may facilitate metastatic cell resistance against
      endothelium-induced oxidative/nitrosative stress. Thus, we investigated in B16M
      F10 cells which molecular mechanisms channel GSH release and whether their
      modulation may influence metastatic activity. GSH efflux was abolished in
      multidrug resistance protein 1 knock-out (MRP-/-1) B16M-F10 transfected with the
      Bcl-2 gene or in MRP-/-1 B16M-F10 cells incubated with l-methionine, which
      indicates that GSH release from B16M-F10 cells is channeled through MRP1 and a
      BCL-2-dependent system (likely related to an l-methionine-sensitive GSH carrier
      previously detected in hepatocytes). The BCL-2-dependent system was identified as
      the cystic fibrosis transmembrane conductance regulator, since monoclonal
      antibodies against this ion channel or H-89 (a protein kinase A-selective
      inhibitor)-induced inhibition of cystic fibrosis transmembrane conductance
      regulator gene expression completely blocked the BCL-2-sensitive GSH release. By
      using a perifusion system that mimics in vivo conditions, we found that GSH
      depletion in metastatic cells can be achieved by using Bcl-2 antisense
      oligodeoxynucleotide- and verapamil (an MRP1 activator)-induced acceleration of
      GSH efflux, in combination with acivicin-induced inhibition of gamma
      glutamyltranspeptidase (which limits GSH synthesis by preventing cysteine
      generation from extracellular GSH). When applied under in vivo conditions, this
      strategy increased tumor cytotoxicity (up to approximately 90%) during B16M-F10
      cell adhesion to the hepatic sinusoidal endothelium.

PMID- 15561711
TI  - Identification of a novel partner of duox: EFP1, a thioredoxin-related protein.
AB  - H(2)O(2) is a crucial substrate of thyroproxidase (TPO) to iodinate thyroglobulin
      and synthesize thyroid hormones in thyroid. ThOX proteins (thyroid oxidase) also
      called Duox are believed to be responsible for H(2)O(2) generation. Duoxs
      expressed in transfected cells do not generate an active system, nor permit their
      membrane localization suggesting that other proteins are required to fulfill
      these functions. In this study, we demonstrate interactions of Duoxs with TPO and
      with p22(phox) without any effect on Duox activity. By yeast two-hybrid method
      using EF-hand fragment of dog Duox1 as the bait we have isolated EFP1 (EF-hand
      binding protein 1), one partner of Duoxs that belongs to the thioredoxin-related
      protein family. EFP1 shares moderate similarities with other members of
      thioredoxin-related proteins, but the characteristic active site and the folding
      structures are well conserved. EFP1 can be co-immunoprecipitated with Duoxs in
      transfected COS cells as well as in primary cultured human thyrocytes. It
      interacts also with TPO but not thyroglobulin. Immunofluorescence studies show
      that EFP1 and Duox proteins are co-localized inside the transfected cells,
      suggesting that EFP1 is not sufficient to induce either the expression of Duox at
      the plasma membrane or to permit H(2)O(2) production. EFP1 and Duox mRNA share
      similar distribution in nine different tissues. These results suggest that EFP1
      could be one of the partners in the assembly of the multiprotein complex
      constituting the thyroid H(2)O(2) generating system but is certainly not
      sufficient to permit H(2)O(2) generation.

PMID- 15561712
TI  - Collagenous transmembrane proteins: recent insights into biology and pathology.

PMID- 15561713
TI  - NF-kappaB- and C/EBPbeta-driven interleukin-1beta gene expression and PAK1
      mediated caspase-1 activation play essential roles in interleukin-1beta release
      from Helicobacter pylori lipopolysaccharide-stimulated macrophages.
AB  - Helicobacter pylori is a Gram-negative microaerophilic bacterium that causes
      chronic gastritis, peptic ulcer, and gastric carcinoma. Interleukin-1beta (IL
      1beta) is one of the potent proinflammatory cytokines elicited by H. pylori
      infection. We have evaluated the role of H. pylori lipopolysaccharide (LPS) as
      one of the mediators of IL-1beta release and dissected the signaling pathways
      leading to LPS-induced IL-1beta secretion. We demonstrate that both the NF-kappaB
      and the C/EBPbeta-binding elements of the IL-1beta promoter drive LPS-induced IL
      1beta gene expression. NF-kappaB activation requires the classical TLR4-initiated
      signaling cascade leading to IkappaB phosphorylation as well as PI-3K/Rac1/p21
      activated kinase (PAK) 1 signaling, whereas C/EBPbeta activation requires PI
      3K/Akt/p38 mitogen-activated protein (MAP) kinase signaling. We observed a direct
      interaction between activated p38 MAP kinase and C/EBPbeta, suggesting that p38
      MAPK is the immediate upstream kinase responsible for activating C/EBPbeta. Most
      important, we observed a role of Rac1/PAK1 signaling in activation of caspase-1,
      which is necessary for maturation of pro-IL-1beta. H. pylori LPS induced direct
      interaction between PAK1 and caspase-1, which was inhibited in cells transfected
      with dominant-negative Rac1. PAK1 immunoprecipitated from lysates of H. pylori
      LPS-challenged cells was able to phosphorylate recombinant caspase-1, but not its
      S376A mutant. LPS-induced caspase-1 activation was abrogated in cells transfected
      with caspase-1(S376A). Taken together, these results suggested a role of PAK1
      induced phosphorylation of caspase-1 at Ser376 in activation of caspase-1. To the
      best of our knowledge our studies show for the first time that LPS-induced
      Rac1/PAK1 signaling leading to caspase-1 phosphorylation is crucial for caspase-1
      activation. These studies also provide detailed insight into the regulation of IL
      1beta gene expression by H. pylori LPS and are particularly important in the
      light of the observations that IL-1beta gene polymorphisms are associated with
      increased risk of H. pylori-associated gastric cancer.

PMID- 15561714
TI  - The leukocyte integrin gene CD11d is repressed by gut-enriched Kruppel-like
      factor 4 in myeloid cells.
AB  - The myeloid-specific leukocyte integrin CD11d encodes the alphaD subunit for the
      alphaDbeta2 receptor. A yeast one-hybrid screen showed that a longer isoform of
      gut-enriched Kruppel-like factor 4 (GKLF) we term GKLFa interacts with the CD11d
      promoter. Purified GST-GKLFa protein was shown to bind within the -61 to -44
      region that overlaps a binding site for the CD11d transcriptional activators Sp1
      and transforming growth factor beta-inducible early gene-1 (TIEG1). Transfection
      of GKLF/GKLFa in myeloid cells reduced CD11d promoter activity, whereas, down
      regulation of GKLF/GKLFa with small interfering RNAs led to up-regulation of
      CD11d expression. Differentiation of myeloid cells with phorbol ester led to
      activation of the CD11d promoter and reduced occupancy of the promoter by
      GKLF/GKLFa but an increased occupancy by TIEG1 in vivo. Binding of GKLF/GKLFa,
      Sp1, and TIEG1 to the CD11d promoter in vivo is dependent on their zinc finger
      DNA binding domains. GKLFa physically associates with the histone deacetylases
      (HDAC) 1 and 2, and both HDACs are bound to the CD11d promoter in vivo but
      released after exposure of myeloid cells to phorbol ester suggesting that
      GKLF/GKLFa recruits HDACs to effect repression.

PMID- 15561715
TI  - Multiple roles for the T7 promoter nontemplate strand during transcription
      initiation and polymerase release.
AB  - Transcription initiation begins with recruitment of an RNA polymerase to a
      promoter. Polymerase-promoter interactions are retained until the nascent RNA is
      extended to 8-12 nucleotides. It has been proposed that accumulation of "strain"
      in the transcription complex and RNA displacement of promoter-polymerase
      interactions contribute to releasing the polymerase from the promoter, and it has
      been further speculated that too strong a promoter interaction can inhibit the
      release step, whereas a weak interaction may facilitate release. We examined the
      effects of partial deletion of the nontemplate strand on release of T7 RNA
      polymerase from the T7 promoter. T7 polymerase will initiate from such partially
      single-stranded promoters but binds them with higher affinity than duplex
      promoters. We found that release on partially single-stranded promoters is
      strongly inhibited. The inhibition of release is not due to an indirect effect on
      transcription complex structure or loss of specific polymerase-nontemplate strand
      interactions, because release on partially single-stranded templates is recovered
      if the interaction with the promoter is weakened by a promoter base substitution.
      This same substitution also appears to allow the polymerase to escape more
      readily from a duplex promoter. Our results further suggest that template
      nontemplate strand reannealing drives dissociation of abortive transcripts during
      initial transcription and that loss of interactions with either the nontemplate
      strand or duplex DNA downstream of the RNA lead to increased transcription
      complex slippage during initiation.

PMID- 15561716
TI  - Inositol diphosphate signaling regulates telomere length.
AB  - Activation of phospholipase C-dependent inositol polyphosphate signaling pathways
      generates distinct messengers derived from inositol 1,4,5-trisphosphate that
      control gene expression and mRNA export. Here we report the regulation of
      telomere length by production of a diphosphorylinositol tetrakisphosphate, PP
      IP4, synthesized by the KCS1 gene product. Loss of PP-IP4 production results in
      lengthening of telomeres, whereas overproduction leads to their shortening. This
      effect requires the presence of Tel1, the yeast homologue of ATM, the protein
      mutated in the human disease ataxia telangiectasia. Our data provide in vivo
      evidence of a regulatory link between inositol polyphosphate signaling and the
      checkpoint kinase family and describe a third nuclear process modulated by
      phospholipase C activation.

PMID- 15561717
TI  - The putative malate/lactate dehydrogenase from Pseudomonas putida is an NADPH
      dependent delta1-piperideine-2-carboxylate/delta1-pyrroline-2-carboxylate
      reductase involved in the catabolism of D-lysine and D-proline.
AB  - A Pseudomonas putida ATCC12633 gene, dpkA, encoding a putative protein annotated
      as malate/L-lactate dehydrogenase in various sequence data bases was disrupted by
      homologous recombination. The resultant dpkA(-) mutant was deprived of the
      ability to use D-lysine and also D-proline as a sole carbon source. The dpkA gene
      was cloned and overexpressed in Escherichia coli, and the gene product was
      characterized. The enzyme showed neither malate dehydrogenase nor lactate
      dehydrogenase activity but catalyzed the NADPH-dependent reduction of such cyclic
      imines as Delta(1)-piperideine-2-carboxylate and Delta(1)-pyrroline-2-carboxylate
      to form L-pipecolate and L-proline, respectively. NADH also served as a hydrogen
      donor for both substrates, although the reaction rates were less than 1% of those
      with NADPH. The reverse reactions were also catalyzed by the enzyme but at much
      lower rates. Thus, the enzyme has dual metabolic functions, and we named the
      enzyme Delta(1)-piperideine-2-carboxylate/Delta(1)-pyrroline-2-carboxylate
      reductase, the first member of a novel subclass in a large family of NAD(P)
      dependent oxidoreductases.

PMID- 15561718
TI  - Systematic identification and analysis of mammalian small ubiquitin-like modifier
      substrates.
AB  - Small ubiquitin-like modifier (SUMO) regulates diverse cellular processes through
      its reversible, covalent attachment to target proteins. Many SUMO substrates are
      involved in transcription and chromatin structure. Sumoylation appears to
      regulate the functions of target proteins by changing their subcellular
      localization, increasing their stability, and/or mediating their binding to other
      proteins. Using an in vitro expression cloning approach, we have identified 40
      human SUMO1 substrates. The spectrum of human SUMO1 substrates identified in our
      screen suggests general roles of sumoylation in transcription, chromosome
      structure, and RNA processing. We have validated the sumoylation of 24 substrates
      in living cells. Analysis of this panel of SUMO substrates leads to the following
      observations. 1) Sumoylation is more efficient in vitro than in living cells.
      Polysumoylation occurs on several substrates in vitro. 2) SUMO isopeptidases have
      little substrate specificity. 3) The SUMO ligases, PIAS1 and PIASxbeta, have
      broader substrate specificities than does PIASy. 4) Although SUMO1 and SUMO2 are
      equally efficiently conjugated to a given substrate in vitro, SUMO1 conjugation
      is more efficient in vivo. 5) Most SUMO substrates localize to the nucleus, and
      sumoylation does not generally affect their subcellular localization. Therefore,
      sumoylation appears to regulate the functions of its substrates through multiple,
      context-dependent mechanisms.

PMID- 15561719
TI  - Human THAP7 is a chromatin-associated, histone tail-binding protein that
      represses transcription via recruitment of HDAC3 and nuclear hormone receptor
      corepressor.
AB  - The identities of signal transducer proteins that integrate histone
      hypoacetylation and transcriptional repression are largely unknown. Here we
      demonstrate that THAP7, an uncharacterized member of the recently identified THAP
      (Thanatos-associated protein) family of proteins, is ubiquitously expressed,
      associates with chromatin, and represses transcription. THAP7 binds
      preferentially to hypoacetylated (un-, mono-, and diacetylated) histone H4 tails
      in vitro via its C-terminal 77 amino acids. Deletion of this domain, or treatment
      of cells with the histone deacetylase inhibitor TSA, which leads to histone
      hyperacetylation, partially disrupts THAP7/chromatin association in living cells.
      THAP7 coimmunoprecipitates with histone deacetylase 3 (HDAC3) and the nuclear
      hormone receptor corepressor (NCoR) and represses transcription as a Gal4 fusion
      protein. Chromatin immunoprecipitation assays demonstrate that these corepressors
      are recruited to promoters in a THAP7 dependent manner and promote histone H3
      hypoacetylation. The conserved THAP domain is a key determinant for full HDAC3
      association in vitro, and both the THAP domain and the histone interaction domain
      are important for the repressive properties of THAP7. Full repression mediated by
      THAP7 is also dependent on NCoR expression. We hypothesize that THAP7 is a dual
      function repressor protein that actively targets deacetylation of histone H3
      necessary to establish transcriptional repression and functions as a signal
      transducer of the repressive mark of hypoacetylated histone H4. This is the first
      demonstration of the transcriptional regulatory properties of a human THAP domain
      protein, and a critical identification of a potential transducer of the
      repressive signal of hypoacetylated histone H4 in higher eukaryotes.

PMID- 15561720
TI  - Mitochondrial O2*- and H2O2 mediate glucose deprivation-induced stress in human
      cancer cells.
AB  - The hypothesis that glucose deprivation-induced cytotoxicity in transformed human
      cells is mediated by mitochondrial O2*- and H2O2 was first tested by exposing
      glucose-deprived SV40-transformed human fibroblasts (GM00637G) to electron
      transport chain blockers (ETCBs) known to increase mitochondrial O2*- and H2O2
      production (antimycin A (AntA), myxothiazol (Myx), or rotenone (Rot)). Glucose
      deprivation (2-8 h) in the presence of ETCBs enhanced parameters indicative of
      oxidative stress (i.e. GSSG and steady-state levels of oxygen-centered radicals)
      as well as cytotoxicity. Glucose deprivation in the presence of AntA also
      significantly enhanced cytotoxicity and parameters indicative of oxidative stress
      in several different human cancer cell lines (PC-3, DU145, MDA-MB231, and HT-29).
      In addition, human osteosarcoma cells lacking functional mitochondrial electron
      transport chains (rho0) were resistant to glucose deprivation-induced
      cytotoxicity and oxidative stress in the presence of AntA. In the absence of
      ETCBs, aminotriazole-mediated inactivation of catalase in PC-3 cells demonstrated
      increases in intracellular steady-state levels of H2O2 during glucose
      deprivation. Finally, in the absence of ETCBs, overexpression of manganese
      containing superoxide dismutase and/or mitochondrial targeted catalase using
      adenoviral vectors significantly protected PC-3 cells from toxicity and oxidative
      stress induced by glucose deprivation with expression of both enzymes providing
      greater protection than was seen with either alone. Overall, these findings
      strongly support the hypothesis that mitochondrial O2*- and H2O2 significantly
      contribute to glucose deprivation-induced cytotoxicity and metabolic oxidative
      stress in human cancer cells.

PMID- 15561721
TI  - Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits
      high density lipoprotein binding and selective lipid uptake.
AB  - Serum amyloid A is an acute phase protein that is carried in the plasma largely
      as an apolipoprotein of high density lipoprotein (HDL). In this study we
      investigated whether SAA is a ligand for the HDL receptor, scavenger receptor
      class B type I (SR-BI), and how SAA may influence SR-BI-mediated HDL binding and
      selective cholesteryl ester uptake. Studies using Chinese hamster ovary cells
      expressing SR-BI showed that (125)I-labeled SAA, both in lipid-free form and in
      reconstituted HDL particles, functions as a high affinity ligand for SR-BI. SAA
      also bound with high affinity to the hepatocyte cell line, HepG2. Alexa-labeled
      SAA was shown by fluorescence confocal microscopy to be internalized by cells in
      a SR-BI-dependent manner. To assess how SAA association with HDL influences HDL
      interaction with SR-BI, SAA-containing HDL was isolated from mice overexpressing
      SAA through adenoviral gene transfer. SAA presence on HDL had little effect on
      HDL binding to SR-BI but decreased (30-50%) selective cholesteryl ester uptake.
      Lipid-free SAA, unlike lipid-free apoA-I, was an effective inhibitor of both SR
      BI-dependent binding and selective cholesteryl ester uptake of HDL. We have
      concluded that SR-BI plays a key role in SAA metabolism through its ability to
      interact with and internalize SAA and, further, that SAA influences HDL
      cholesterol metabolism through its inhibitory effects on SR-BI-mediated selective
      lipid uptake.

PMID- 15561722
TI  - Accumulation of free ADP-ribose from mitochondria mediates oxidative stress
      induced gating of TRPM2 cation channels.
AB  - TRPM2 is a member of the transient receptor potential melastatin-related (TRPM)
      family of cation channels, which possesses both ion channel and ADP-ribose
      hydrolase functions. TRPM2 has been shown to gate in response to oxidative and
      nitrosative stresses, but the mechanism through which TRPM2 gating is induced by
      these types of stimuli is not clear. Here we show through structure-guided
      mutagenesis that TRPM2 gating by ADP-ribose and both oxidative and nitrosative
      stresses requires an intact ADP-ribose binding cleft in the C-terminal nudix
      domain. We also show that oxidative/nitrosative stress-induced gating can be
      inhibited by pharmacological reagents predicted to inhibit NAD hydrolysis to ADP
      ribose and by suppression of ADP-ribose accumulation by cytosolic or
      mitochondrial overexpression of an enzyme that specifically hydrolyzes ADP
      ribose. Overall, our data are most consistent with a model of oxidative and
      nitrosative stress-induced TRPM2 activation in which mitochondria are induced to
      produce free ADP-ribose and release it to the cytosol, where its subsequent
      accumulation induces TRPM2 gating via interaction within a binding cleft in the C
      terminal NUDT9-H domain of TRPM2.

PMID- 15561723
TI  - Exposure to hypoxia rapidly induces mitochondrial channel activity within a
      living synapse.
AB  - One of the earliest effects of hypoxia on neuronal function is to produce a run
      down of synaptic transmission, and more prolonged hypoxia results in neuronal
      death. An increase in the permeability of the outer mitochondrial membrane,
      controlled by BCL-2 family proteins, occurs in response to stimuli that trigger
      cell death. By patch clamping mitochondrial membranes inside the presynaptic
      terminal of a squid giant synapse, we have now found that several minutes of
      hypoxia trigger the opening of large multiconductance channels. The channel
      activity is induced concurrently with the attenuation of synaptic responses that
      occurs under hypoxic conditions. Hypoxia-induced channels are inhibited by NADH,
      an agent that inhibits large conductance channels produced by a pro-apoptotic
      fragment of BCL-xL in these synaptic mitochondria. The appearance of hypoxia
      induced channels was also prevented by the caspase/cysteine protease inhibitor
      benzyloxycarbonyl-VAD-fluoromethyl ketone (Z-VAD-fmk), which inhibits proteolysis
      of BCL-xL during hypoxia. Both NADH and Z-VAD-fmk reduced significantly the rate
      of decline of synaptic responses during hypoxia. Our results indicate that an
      increase in outer mitochondrial channel activity is a very early event in the
      response of neurons to hypoxia and suggest that this increase in activity may
      contribute to the decline in synaptic function during hypoxia.

PMID- 15561724
TI  - NDPK2 as a signal transducer in the phytochrome-mediated light signaling.
AB  - Nucleoside-diphosphate kinase (NDPK) 2 in Arabidopsis has been identified as a
      phytochrome-interacting protein by using the C-terminal domain of phytochrome A
      (PhyA) as the bait in yeast two-hybrid screening. The far-red light-absorbing
      form of phytochrome (Pfr) A stimulates NDPK2 gamma-phosphate exchange activity in
      vitro. To better understand the multiple functions of NDPK and its role in
      phytochrome-mediated signaling, we characterized the interaction between
      phytochrome and NDPK2. Domain studies revealed that PER-ARNT-SIM domain A in the
      C-terminal domain of phytochrome is the binding site for NDPK2. Additionally,
      phytochrome recognizes both the NDPK2 C-terminal fragment and the NDPK2 hexameric
      structure to fulfill its binding. To illustrate the mechanism of how the Pfr form
      of phytochrome stimulates NDPK2, His-197-surrounding residue mutants were made
      and tested. Results suggested that the H-bonding with His-197 inside the
      nucleotide-binding pocket is critical for NDPK2 functioning. The pH dependence
      profiles of NDPK2 indicated that mutants with different activities from the wild
      type have different pK(a) values of His-197 and that NDPK2 hyperactive mutants
      possess lower pK(a) values. Because a lower pK(a) value of His-197 accelerates
      NDPK2 autophosphorylation and the phospho-transfer between the phosphorylated
      NDPK2 and its kinase substrate, we concluded that the Pfr form of phytochrome
      stimulates NDPK2 by lowering the pK(a) value of His-197.

PMID- 15561725
TI  - C-terminal ECFP fusion impairs synaptotagmin 1 function: crowding out
      synaptotagmin 1.
AB  - To allow the monitoring of synaptotagmin 1 trafficking in vivo, we generated
      transgenic mice expressing a synaptotagmin 1-enhanced cyan fluorescent protein
      (ECFP) fusion protein under control of the Thy1 promoter. Transgenic
      synaptotagmin 1-ECFP is expressed throughout the brain where it localizes to
      synapses and marks synapses in vivo. However, when we crossed transgenic
      synaptotagmin 1-ECFP mice with synaptotagmin 1 knock-out mice, we detected no
      rescue of survival or function. Furthermore, viral overexpression of
      synaptotagmin 1-ECFP in synaptotagmin 1-deficient neurons failed to restore
      normal Ca2+-triggered release, whereas overexpression of wild type synaptotagmin
      1 did so efficiently. To determine whether synaptotagmin 1-ECFP is non-functional
      because the ECFP-fusion interferes with its biochemical activities, we measured
      Ca2+-independent binding of synaptotagmin 1-ECFP to SNARE complexes, and Ca2+
      dependent binding of synaptotagmin 1-ECFP to phospholipids and to itself.
      Although the apparent Ca2+ affinity of synaptotagmin 1-ECFP was decreased
      compared with wild type synaptotagmin 1, we observed no major changes in Ca2+
      dependent or -independent activities, indicating that the non-functionality of
      the synaptotagmin 1-ECFP fusion protein was not because of inactivation of its
      biochemical properties. These data suggest that synaptotagmin 1-ECFP is suitable
      for monitoring synaptic vesicle traffic in vivo because the synaptotagmin 1-ECFP
      marks synaptic vesicles without participating in exocytosis. In addition, the
      data demonstrate that synaptotagmin 1 function requires a free C terminus,
      possibly because of spatial constraints at the release sites.

PMID- 15561726
TI  - Mouse p56 blocks a distinct function of eukaryotic initiation factor 3 in
      translation initiation.
AB  - Members of the p56 family of mammalian proteins are strongly induced in virus
      infected cells and in cells treated with interferons or double-stranded RNA.
      Previously, we have reported that human p56 inhibits initiation of translation by
      binding to the "e" subunit of eukaryotic initiation factor 3 (eIF3) and
      subsequently interfering with the eIF3/eIF2.GTP.Met-tRNAi (ternary complex)
      interaction. Here we report that mouse p56 also interferes with eIF3 functions
      and inhibits translation. However, the murine protein binds to the "c" subunit,
      not the "e" subunit, of eIF3. Consequently, it has only a marginal effect on
      eIF3.ternary complex interaction. Instead, the major inhibitory effect of mouse
      p56 is manifested at a different step of translation initiation, namely the
      binding of eIF4F to the 40 S ribosomal subunit.eIF3.ternary complex. Thus, mouse
      and human p56 proteins block different functions of eIF3 by binding to its
      different subunits.

PMID- 15561727
TI  - Retrograde plastid redox signals in the expression of nuclear genes for
      chloroplast proteins of Arabidopsis thaliana.
AB  - Excitation imbalances between photosystem I and II generate redox signals in the
      thylakoid membrane of higher plants which induce acclimatory changes in the
      structure of the photosynthetic apparatus. They affect the accumulation of
      reaction center and light-harvesting proteins as well as chlorophylls a and b. In
      Arabidopsis thaliana the re-adjustment of photosystem stoichiometry is mainly
      mediated by changes in the number of photosystem I complexes, which are
      accompanied by corresponding changes in transcripts for plastid reaction center
      genes. Because chloroplast protein complexes contain also many nuclear encoded
      components we analyzed the impact of such photosynthetic redox signals on nuclear
      genes. Light shift experiments combined with application of the electron
      transport inhibitor 3-(3',4'-dichlorophenyl)-1,1'-dimethyl urea have been
      performed to induce defined redox signals in the thylakoid membrane. Using DNA
      macroarrays we assessed the impact of such redox signals on the expression of
      nuclear genes for chloroplast proteins. In addition, studies on mutants with
      lesions in cytosolic photoreceptors or in chloroplast-to-nucleus communication
      indicate that the defective components in the mutants are not essential for the
      perception and/or transduction of light-induced redox signals. A stable redox
      state of glutathione suggest that neither glutathione itself nor reactive oxygen
      species are involved in the observed regulation events pointing to the thylakoid
      membrane as the main origin of the regulatory pathways. Our data indicate a
      distinct role of photosynthetic redox signals in the cellular network regulating
      plant gene expression. These redox signals appear to act independently and/or
      above of cytosolic photoreceptor or known chloroplast-to-nucleus communication
      avenues.

PMID- 15561728
TI  - Characterization of gel-separated glycoproteins using two-step proteolytic
      digestion combined with sequential microcolumns and mass spectrometry.
AB  - Protein glycosylation can be vital for changing the function or physiochemical
      properties of a protein. Abnormal glycosylation can lead to protein malfunction,
      resulting in severe diseases. Therefore, it is important to develop techniques
      for characterization of such modifications in proteins at a sensitivity level
      comparable with state-of-the-art proteomics. Whereas techniques exist for
      characterization of high abundance glycoproteins, no single method is presently
      capable of providing information on both site occupancy and glycan structure on a
      single band excised from an electrophoretic gel. We present a new technique that
      allows characterization of low amounts of glycoproteins separated by gel
      electrophoresis. The method takes advantage of sequential specific and
      nonspecific enzymatic treatment followed by selective purification and
      characterization of the glycopeptides using graphite powder microcolumns in
      combination with mass spectrometry. The method is faster and more sensitive than
      previous approaches and is compatible with proteomic studies.

PMID- 15561729
TI  - Proteome analysis of the human mitotic spindle.
AB  - The accurate distribution of sister chromatids during cell division is crucial
      for the generation of two cells with the same complement of genetic information.
      A highly dynamic microtubule-based structure, the mitotic spindle, carries out
      the physical separation of the chromosomes to opposite poles of the cells and,
      moreover, determines the cell division cleavage plane. In animal cells, the
      spindle comprises microtubules that radiate from the microtubule organizing
      centers, the centrosomes, and interact with kinetochores on the chromosomes.
      Malfunctioning of the spindle can lead to chromosome missegregation and hence
      result in aneuploidy, a hallmark of most human cancers. Despite major progress in
      deciphering the temporal and spatial regulation of the mitotic spindle, its
      composition and function are not fully understood. A more complete inventory of
      spindle components would therefore constitute an important advance. Here we
      describe the purification of human mitotic spindles and their analysis by MS/MS.
      We identified 151 proteins previously known to associate with the spindle
      apparatus, centrosomes, and/or kinetochores and 644 other proteins, including 154
      uncharacterized components that did not show obvious homologies to known proteins
      and did not contain motifs indicative of a particular localization. Of these
      uncharacterized proteins, 17 were tagged and localized in transfected mitotic
      cells, resulting in the identification of six genuine spindle components
      (KIAA0008, CdcA8, KIAA1187, FLJ12649, FLJ90806, and C20Orf129). This study
      illustrates the strength of a proteomic approach for the analysis of isolated
      human spindles and identifies several novel spindle components for future
      functional studies.

PMID- 15561730
TI  - Congenital anomaly surveillance in England--ascertainment deficiencies in the
      national system.
AB  - OBJECTIVE: Firstly, to assess the completeness of ascertainment in the National
      Congenital Anomaly System (NCAS), the basis for congenital anomaly surveillance
      in England and Wales, and its variation by defect, geographical area, and
      socioeconomic deprivation. Secondly, to assess the impact of the lack of data on
      pregnancies terminated because of fetal anomaly. DESIGN: Comparison of the NCAS
      with four local congenital anomaly registers in England. SETTING: Four regions in
      England covering some 109,000 annual births. PARTICIPANTS: Cases of congenital
      anomalies registered in the NCAS (live births and stillbirths) and independently
      registered in the four local registers (live births, stillbirths, fetal losses
      from 20 weeks' gestation, and pregnancies terminated after prenatal diagnosis of
      fetal anomaly). MAIN OUTCOME MEASURE: The ratio of cases identified by the
      national register to those in local registry files, calculated for different
      specified anomalies, for whole registry areas, and for hospital catchment areas
      within registry boundaries. RESULTS: Ascertainment by the NCAS (compared with
      data from local registers, from which terminations of pregnancy were removed) was
      40% (34% for chromosomal anomalies and 42% for non-chromosomal anomalies) and
      varied markedly by defect, by local register, and by hospital catchment area, but
      not by area deprivation. When terminations of pregnancy were included in the
      register data, ascertainment by NCAS was 27% (19% for chromosomal anomalies and
      31% for non-chromosomal anomalies), and the geographical variation was of a
      similar magnitude. CONCLUSION: The surveillance of congenital anomalies in
      England is currently inadequate because ascertainment to the national register is
      low and non-uniform and because no data exist on termination of pregnancy
      resulting from prenatal diagnosis of fetal anomaly.

PMID- 15561731
TI  - Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in
      osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials.
AB  - OBJECTIVE: To estimate the analgesic efficacy of non-steroidal anti-inflammatory
      drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in
      patients with osteoarthritis of the knee. DESIGN: Systematic review and meta
      analysis of randomised placebo controlled trials. STUDIES REVIEWED: 23 trials
      including 10 845 patients, median age of 62.5 years. 7807 patients received
      adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline
      pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average
      duration of symptoms was 8.2 years. MAIN OUTCOME MEASURE: Change in overall
      intensity of pain. RESULTS: Methodological quality of trials was acceptable, but
      13 trials excluded patients before randomisation if they did not respond to
      NSAIDs. One trial provided long term data for pain that showed no significant
      effect of NSAIDs compared with placebo at one to four years. The pooled
      difference for pain on visual analogue scale in all included trials was 10.1 mm
      (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13
      weeks. The results were heterogeneous, and the effect size for pain reduction was
      0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude
      non-responders to NSAID treatment the results were homogeneous, with an effect
      size for pain reduction of 0.23 (0.15 to 0.31). CONCLUSION: NSAIDs can reduce
      short term pain in osteoarthritis of the knee slightly better than placebo, but
      the current analysis does not support long term use of NSAIDs for this condition.
      As serious adverse effects are associated with oral NSAIDs, only limited use can
      be recommended.

PMID- 15561732
TI  - Concealment of drugs in food and beverages in nursing homes: cross sectional
      study.
AB  - OBJECTIVE: To examine the practice of concealing drugs in patients' foodstuff in
      nursing homes. DESIGN: Cross sectional study with data collected by structured
      interview. SETTING: All five health regions in Norway. PARTICIPANTS: Professional
      carers of 1362 patients in 160 regular nursing home units and 564 patients in 90
      special care units for people with dementia. MAIN OUTCOME MEASURES: Frequency of
      concealment of drugs; who decided to conceal the drugs; how this practice was
      documented in the patients' records; and what types of drugs were given this way.
      RESULTS: 11% of the patients in regular nursing home units and 17% of the
      patients in special care units for people with dementia received drugs mixed in
      their food or beverages at least once during seven days. In 95% of cases, drugs
      were routinely mixed in the food or beverages. The practice was documented in
      patients' records in 40% (96/241) of cases. The covert administration of drugs
      was more often documented when the physician took the decision to hide the drugs
      in the patient's foodstuff (57%; 27/47) than when the person who made the
      decision was unknown or not recorded (23%; 7/30). Patients who got drugs covertly
      more often received antiepileptics, antipsychotics, and anxiolytics compared with
      patients who were given their drugs openly. CONCLUSIONS: The covert
      administration of drugs is common in Norwegian nursing homes. Routines for such
      practice are arbitrary, and the practice is poorly documented in the patients'
      records.

PMID- 15561733
TI  - Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in
      first births: prospective study.
AB  - OBJECTIVE: To investigate the relation of diastolic blood pressure in pregnancy
      with birth weight and perinatal mortality. DESIGN: Prospective study. SETTING: 15
      maternity units in one London health region, 1988-2000. PARTICIPANTS: 210 814
      first singleton births of babies weighing more than 200 g among mothers with no
      hypertension before 20 weeks' gestation and without proteinuria, delivering
      between 24 and 43 weeks' gestation. MAIN OUTCOME MEASURES: Birth weight and
      perinatal mortality. RESULTS: The mean (SD) birth weight of babies born to
      mothers with no hypertension before 20 weeks' gestation or proteinuria was 3282 g
      (545 g) and there were 1335 perinatal deaths, compared with 94 perinatal deaths
      among women with proteinuria or a history of hypertension. Diastolic blood
      pressure at booking for antenatal checks was progressively higher from weeks 34
      to 40 of gestation. The birth weight of babies being delivered after 34 weeks was
      highest for highest recorded maternal diastolic blood pressures of between 70 and
      80 mm Hg and lower for blood pressures outside this range. Both low and high
      diastolic blood pressures were associated with statistically significantly higher
      perinatal mortality. Using a linear quadratic model, 94 of 825 (11.4%) perinatal
      deaths could be attributed to mothers having blood pressure differing from the
      optimal blood pressure (82.7 mm Hg) predicted by the fitted model. Most of these
      excess deaths occurred with blood pressures below the optimal value. CONCLUSIONS:
      Both low and high diastolic blood pressures in women during pregnancy are
      associated with small babies and high perinatal mortality.

PMID- 15561734
TI  - Localized scleroderma is an autoimmune disorder.
AB  - OBJECTIVES: There have been many studies suggesting that localized scleroderma
      has a strong autoimmune background, although the lesions are usually limited to
      the skin and subcutaneous tissue. Here we summarize previous data on the
      autoimmunity of localized scleroderma, mostly published in the last two decades,
      because there has not been a review paper summarizing autoimmunity in this
      disorder. METHODS: We classified the previous reports into three categories:
      antinuclear antibodies; cytokine and soluble receptors; and cell adhesion
      molecules and cell surface molecules. In each category, we introduce the
      important investigations. RESULTS: High frequencies of antinuclear antibodies,
      detected by the indirect immunofluorescence method using cultured cells, are
      confirmed by many groups. The major autoantigens have been revealed to be
      histones. Recently, anti-topoisomerase II alpha antibody has been found to be
      detected highly frequently in localized scleroderma, while anti-topoisomerase I
      antibody, which is highly specific for systemic sclerosis, has not been detected
      in any case of localized scleroderma. In other studies, elevated serum cytokines
      and cell adhesion molecules suggest the immunoactivation of localized
      scleroderma. CONCLUSIONS: Many previous studies conclude that localized
      scleroderma involves autoimmune abnormalities and is one of the organ-specific
      autoimmune disorders targeting mainly skin, although the types of autoimmune
      abnormality are different from systemic sclerosis.

PMID- 15561735
TI  - Screening for pulmonary hypertension in systemic sclerosis: the longitudinal
      development of tricuspid gradient in 227 consecutive patients, 1992-2001.
AB  - OBJECTIVE: To evaluate the longitudinal development of the tricuspid gradient
      (TG) for screening for pulmonary arterial hypertension (PAH) in systemic
      sclerosis (SSc). METHODS: Doppler echocardiography was performed 506 times in
      order to estimate TG in 227 consecutive patients with SSc. The value of
      biochemical markers for predicting TG levels and development was assessed through
      analyses of pro-brain natriuretic peptide (proBNP), calcitonin-gene related
      peptide, thrombomodulin and von Willebrand factor in 76 patients with a
      borderline increase in TG, defined as TG 24-38 mmHg, and for the purpose of
      comparison also in 10 patients with a normal TG (< 23 mmHg) and in 10 patients
      with increased TG (TG > 38 mmHg). RESULTS: TG > 23 mmHg was found in 102 patients
      (44.9%) at the first assessment point and in 139 patients (61.2%) respectively,
      cumulatively at follow-up. TG values > 33 mmHg were measured in 24 patients
      (10.6%) initially and in 38 patients (16.7%) cumulatively in a subsequent
      assessment. Age and the presence of interstitial lung disease (ILD) were
      associated with more frequent occurrence of TG > 23 and > 33 mmHg initially and
      at follow-up, but were not associated with progression rate. The change in TG
      (mean +/- S.D.) was 1.34 +/- 4.55 mmHg/yr. ProBNP correlated to TG. CONCLUSION:
      An increased TG, indicating possible PAH, is common and progressive in SSc. Age
      and ILD increase the risk of increased TG. Patients with or without ILD have
      similar progression of TG. ProBNP has potential as an adjunct to TG in selecting
      patients eligible for invasive treatment.

PMID- 15561736
TI  - Anti-TNF-alpha therapies: they are all the same (aren't they?).

PMID- 15561737
TI  - Long-term efficacy and safety of etanercept after readministration in patients
      with active ankylosing spondylitis.
AB  - OBJECTIVES: Treatment of ankylosing spondylitis (AS) with the tumour necrosis
      factor alpha (TNF-alpha) receptor fusion protein etanercept has shown efficacy in
      patients with active disease in randomized controlled trials (RCTs) for limited
      periods. The objective of the study was to assess the long-term efficacy and
      safety of etanercept over 1 yr, including discontinuation and readministration.
      METHODS: In this 54-week open observational study, 26 AS patients received 25 mg
      etanercept subcutaneously twice weekly after several months of discontinuation
      following a 6-month RCT with the same agent. All patients who developed high
      disease activity after cessation of etanercept, defined as a Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) > or = 4 and pain > or = 4 on a
      numerical rating scale, entered the study. Standard assessment tools, such as the
      Bath Ankylosing Spondylitis functional index (BASFI), were used. An intention-to
      treat (ITT) and a completer analysis were performed. The results were compared
      with the baseline values of the open study. RESULTS: Out of the initial 30
      patients, 26 (87%) were eligible for the open extension study after a mean of
      about 27 weeks. At week 54, 23/26 patients (88%) were still on treatment with
      etanercept. The ITT analysis showed that 58% (95% confidence interval 39-74%) of
      the patients achieved a 50% improvement of BASDAI at week 54. According to the
      Assessments in Ankylosing Spondylitis working group criteria, 8/26 patients (31%)
      were in partial remission at week 54. Function, metrology and quality of life
      improved significantly. Only one patient had a serious adverse event that
      resulted in discontinuation. CONCLUSIONS: This study shows that treatment with
      etanercept is efficacious and safe after readministration over 1 yr in patients
      with active AS not taking DMARDs or steroids.

PMID- 15561738
TI  - The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to
      pathogenesis of rheumatoid arthritis.
AB  - OBJECTIVE: The gene for peptidylarginine deiminase 4 (PADI4) has been found to be
      closely associated with rheumatoid arthritis (RA). Peptidylarginine deiminase
      (PADI) catalyses the post-translational modification of peptidylarginine to
      citrulline, a reaction known as citrullination. PADI extracted from rabbit muscle
      has been reported to citrullinate antithrombin, a principal plasma inhibitor of
      thrombin. Thrombin is known to induce angiogenesis, fibrin formation and
      inflammation, the primary events of the RA joint. Here, we investigate whether
      human PADI4 can inhibit antithrombin by catalysing antithrombin citrullination
      and how the enzyme is involved in RA pathogenesis. METHODS: Antithrombin was
      incubated with recombinant PADI4 protein, and the inactivation of antithrombin
      was determined by reduction of its thrombin-inhibiting activity. Citrullination
      of antithrombin was detected by western blotting and enzyme-linked immunosorbent
      assay (ELISA). In addition, the citrullination level, activity and concentration
      of antithrombin in RA plasma were investigated by sandwich ELISA. RESULTS:
      Incubation of antithrombin with PADI4 resulted in loss of thrombin-inhibitory
      activity and in citrullination of antithrombin. RA plasma showed higher levels of
      citrullinated antithrombin than controls with non-arthritis disease and healthy
      individuals. CONCLUSION: The results indicate that PADI4 could inactivate
      antithrombin through citrullination. The abnormal expression or activation of
      PADI4 in RA synovium is suggested to be responsible for the high level of
      citrullinated antithrombin in RA plasma. Local inhibition of antithrombin
      activity in RA synovium might lead to the excessive angiogenesis, fibrin
      deposition and inflammation of the tissue.

PMID- 15561739
TI  - Cataracts in retired actinide-exposed radiation workers.
AB  - Radiation-induced cataracts are predominantly of the posterior sub-capsular (PSC)
      type, whereas about 90% of age-related cataracts are of other types. Retired
      workers, likely to have transuranic body burdens, from three DOE-supported
      installations were questioned regarding their eye-care history and asked for
      permission to contact their eye-care providers regarding any cataracts. In 97
      cases with lifetime exposure records 20 cases (20.6%) were reported to have PSC
      cataracts. However, of 24 individuals with recorded lifetime doses of 200-600
      mSv, nine (37.5%) had PSC cataracts, compared with 15.1% of 73 cases with doses
      of less than 200 mSv. This difference is statistically significant at the 5%
      level.

PMID- 15561740
TI  - Uranium isotopes in public drinking water and dose assessment for man in Poland.
AB  - 238U, 234U and 235U were determined in tap water from municipal water pipes that
      drew their supply from surface water or ground water in various locations in
      Poland. Average activity concentrations of 238U, 234U and 235U in tap water from
      surface water were 9.6 +/- 7.1, 12.8 +/- 9.7 and 0.41 +/- 0.31 Bq m(-3),
      respectively, whereas from ground water they were 4.5 +/- 6.0, 5.7 +/- 6.9 and
      0.19 +/- 0.27 Bq m(-3), respectively. Activity concentrations of 234U were higher
      than 238U. Ratios of 234U/238U ranged from 1.07 to 2.60, indicating the lack of
      equilibrium between these isotopes. The average 235U/238U ratio was 0.043 +/-
      0.008, being close to 0.046 for natural uranium. Average annual intake with water
      and food was 7.6 +/- 5.1 Bq for 238U and 9.5 +/- 6.6 Bq for 234U. Annual
      committed effective doses calculated from these intakes for adults were 0.34 +/-
      0.23 and 0.47 +/- 0.32 microSv, respectively; 235U contributed to the total dose
      from the uranium isotopes by about 2%.

PMID- 15561741
TI  - Comparative analysis of the in and ex situ determination of environmental
      radiation and dosimetry levels.
AB  - A method is proposed to determine the activities of natural and artificial gamma
      emitting radionuclides in soils using in situ spectrometry that is validated with
      conventional low-background laboratory gamma spectrometry. From the two sets of
      results, the dose-equivalent rate levels in the environment were reproduced and
      we are thus able to determine the principal components of those levels.

PMID- 15561742
TI  - Radon monitor calibration using NIST radon emanation standards: steady flow
      method.
AB  - The National Institute of Standards and Technology (NIST) polyethylene
      encapsulated 226Ra/222Rn emanation (PERE) standards (old SRM 4968 and new SRMs
      4971, 4972, and 4973) provide precise radon emanation rate, certified to a high
      degree of accuracy (approximately to 2%). Two new SRM 4973 standards containing
      totally 1036 Bq (0.028 microCi) of 226Ra, emanate 0.114 Bq (3.08 pCi) of 222Rn
      per min. Air passing over such sources at a flow rate of 1 l min(-1) will have a
      radon concentration of 114 Bq m(-3) (3.08 pCi l(-1)). This paper describes a
      practical calibration system and the actual calibration verification data
      obtained at different flow rates, for E-PERM passive radon monitors, Femto-Tech
      and Alpha Guard Continuous Radon Monitors. The use of such an affordable and easy
      to use system by the manufacturers and users of radon measurement devices will
      bring uniform standards with traceability to a NIST standard source and is
      considered an important step in standardising radon measurement methods.

PMID- 15561743
TI  - Messenger RNA expression of target genes in the urinary sediment of patients with
      chronic kidney diseases.
AB  - BACKGROUND: The degree of renal scarring in kidney biopsy is an important
      prognostic factor in patients with chronic kidney diseases. We hypothesize that
      gene expression in the urinary sediment reflects the degree of renal damage.
      METHODS: We studied 29 patients with chronic kidney disease who underwent kidney
      biopsy (12 immunoglobulin-A nephropathy and 17 glomerulosclerosis) and 10 healthy
      controls. The mRNA expressions of a panel of target genes in urinary sediment
      were measured by real-time quantitative polymerase chain reaction. The results
      were compared with the degree of histological damage and renal function decline.
      RESULTS: There were significant differences in the urinary expression of
      transforming growth factor-beta (TGF-beta), monocyte chemotactic protein-1 (MCP
      1) and collagen IV between disease groups and controls. Urinary TGF-beta mRNA
      expression correlated significantly with estimated glomerular filtration rate (r
      = -0.412, P = 0.029) and the degree of tubulointerstitial scarring (r = 0.418, P
      = 0.024). Urinary MCP-1 expression correlated with the degree of
      glomerulosclerosis (r = 0.450, P = 0.014), but not tubulointerstitial scarring.
      Urinary MCP-1 expression correlated with its corresponding level by enzyme-linked
      immunosorbent assay (ELISA) (r = 0.650, P<0.001), but TGF-beta expression did not
      correlate with its ELISA level. Urinary TGF-beta gene expression correlated with
      its intra-renal expression in glomeruli (r = 0.701, P<0.001) and
      tubulointerstitium (r = 0.573, P = 0.001) by immunohistochemistry, while urinary
      MCP-1 gene expression correlated with its staining in glomeruli (r = 0.576, P =
      0.001) but not tubulointerstitium. After 12 months, there was a significant
      inverse correlation between the rate of renal function decline and urinary
      expression of connective tissue growth factor (r = -0.471, P = 0.010) and
      collagen I (r = -0.399, P = 0.032), but not TGF-beta or MCP-1. CONCLUSIONS:
      Amongst the target genes examined, the mRNA expression of TGF-beta in urinary
      sediment correlated with renal function, the degree of histological damage and
      intra-renal level in patients with chronic kidney diseases. Measurement of TGF
      beta mRNA expression in urine may be a useful non-invasive tool for assessing the
      severity of renal damage in patients with chronic kidney diseases.

PMID- 15561744
TI  - Pirfenidone and candesartan ameliorate morphological damage in mild chronic anti
      GBM nephritis in rats.
AB  - BACKGROUND: The antifibrotic substance pirfenidone and the angiotensin II type I
      receptor antagonist candesartan cilexetil, given alone and in combination, were
      tested in rats with chronic anti-glomerular basement membrane glomerulonephritis
      (anti-GBM GN). METHODS: Male Wistar rats with anti-GBM GN were treated for 8
      weeks with candesartan (4 mg/kg body weight/day), pirfenidone (500 mg/kg body
      weight/day) or a combination of both drugs. One GN group received no treatment
      and untreated non-GN-rats were used as controls. Blood pressure and urinary
      protein excretion were measured after 3 and 7 weeks. Kidney histology was
      complemented by ultrastructural investigation and by quantification of collagen
      Ialpha mRNA. RESULTS: The percentage of glomeruli with adsorption droplets in
      podocytes correlated well with the amount of proteinuria (r = 0.873, P<0.01) and
      was significantly lowered in rats treated with candesartan (8.3 vs GN 24.6%),
      pirfenidone (9.8%) and combined treatment (2.6%, P<0.05 vs candesartan alone). A
      comparable lowering was seen for segmental sclerosis (GN 11%, candesartan 0.7%,
      P<0.05 vs GN, pirfenidone 1.8%, P = 0.09 vs GN, candesartan/pirfenidone 0.1%,
      P>0.5 vs candesartan alone). Cortical collagen Ialpha mRNA expression was
      significantly decreased in all treatment groups. Ultrastructural investigation
      showed an amelioration of basement membrane alterations and podocyte damage in
      the treatment groups. Candesartan caused significant blood pressure reduction and
      the effect was significantly enhanced by combination therapy after 3 weeks. Rats
      treated with pirfenidone showed blood pressure values similar to control rats.
      CONCLUSION: Pirfenidone has a beneficial effect on morphological changes in anti
      GBM GN comparable with candesartan although with a trend to slightly better
      results with candesartan treatment. Moreover, our results suggest an additive
      effect of combination treatment.

PMID- 15561745
TI  - Birth defects in children conceived by ICSI compared with children conceived by
      other IVF-methods; a meta-analysis.
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a method of assisted
      reproductive technology that involves the selection of a single sperm cell and
      the manual injection of this cell into the egg. The lack of relevant experimental
      studies, the nature of the technology involving non-natural selection of the
      fertilizing sperm, and possible damage to the egg have caused concern that ICSI
      could increase the risk of birth defects. Data from available cohort studies
      comparing ICSI with standard in vitro fertilization (IVF) should be combined to
      evaluate the risks involved with ICSI. METHODS: We reviewed more than 2500 titles
      and abstracts containing keywords related to ICSI and identified 22 scientific
      articles with data on birth defects among ICSI-births. A total of four peer
      reviewed, non-overlapping prospective cohort studies provided reliable and
      comparable data on birth defects both for children conceived by ICSI and children
      conceived by standard IVF. These studies included a total of 5395 children born
      after ICSI. RESULTS: The pooled estimate of the risk of a major birth defect was
      a 1.12-fold increase after ICSI when compared with standard IVF (risk ratio =
      1.12, 95% confidence interval (CI): 0.97-1.28, P = 0.12). There was no marked
      heterogeneity of risk ratios between these studies (P = 0.10). We found no
      significantly increased risks after ICSI for any of the categories cardiovascular
      defects, musculoskeletal defects, hypospadias, neural tube defects, or oral
      clefts. CONCLUSIONS: Our analysis does not indicate that the ICSI-procedure
      represents significant additional risks of major birth defects in addition to the
      risk involved in standard IVF. The data was limited, particularly on risks of
      specific categories of defects.

PMID- 15561746
TI  - Regression analysis of trends in mortality from hepatocellular carcinoma in
      Japan, 1972-2001.
AB  - BACKGROUND: In Japan, higher mortality rates from hepatocellular carcinoma (HCC)
      have been observed than in any other industrialized country and the reported
      numbers of deaths due to HCC have increased significantly in recent years. We
      assessed whether there was a real increase in mortality from HCC and which
      factors contributed to the recent increasing trends of the number of deaths from
      HCC. METHODS: Poisson regression models were used to analyse panel data for the
      period 1972-2001. RESULTS: In both sexes, age-standardized mortality rates from
      HCC increased significantly over the past three decades. Among males the annual
      percentage increase in age-adjusted mortality rates was approximately 1-3% during
      the period 1972-96. On the other hand, female mortality trends were less clear.
      The estimated birth cohort effects suggested that there was a peak in the
      mortality risk among the cohorts born during the period 1927-36, which
      corresponded to those aged between 50-64 years during the period 1987-96. This
      was the period when a large increase of both age-specific mortality rates among
      older age groups and age-standardized mortality rates were observed particularly
      among males. CONCLUSIONS: This study shows that an upward trend of mortality from
      HCC in Japan was primarily due to the effects among birth cohorts born around
      1930, which are consistent with the pattern of past exposure to hepatitis C
      virus. The cohort effects have contributed to a large increase in mortality from
      HCC in recent years and the number of deaths from HCC is expected to increase by
      2010-15.

PMID- 15561747
TI  - Baseline self-perceived risk of HIV infection independently predicts the rate of
      HIV seroconversion in a prospective cohort of injection drug users.
AB  - BACKGROUND: The identification of individuals at the highest risk of human
      immunodeficiency virus (HIV) infection is critical for targeting prevention
      strategies. We evaluated self-perceived risk of HIV infection and rates of
      subsequent HIV seroconversion among a prospective cohort study of injection drug
      users (IDUs). METHODS: We performed an analysis of the time to HIV infection
      among 994 baseline HIV negative IDUs enrolled in the Vancouver injection drug
      users study (VIDUS). IDUs were stratified based on their baseline self-perceived
      risk of HIV seroconversion (higher than others vs same or lower). Kaplan-Meier
      methods were used to estimate cumulative HIV incidence rates and Cox regression
      was used to determine adjusted relative hazards for HIV seroconversion. RESULTS:
      At the end of 24 months after enrolment into the cohort, the cumulative HIV
      incidence rate was significantly elevated among the 5.9% of the sample who
      perceived their risk for HIV infection to be higher at baseline (26.6% vs 7.8%
      log-rank P < 0.001). In a Cox model that adjusted for all variables that were
      associated with the time to HIV infection in univariate analyses, a higher
      baseline self-perceived risk of acquiring HIV infection (relative hazard RH: 2.48
      [95% Confidence interval (CI): 1.51, 4.10]; P = 0.004) remained independently
      associated with time to HIV seroconversion. CONCLUSIONS: IDUs' perception of
      their risk for HIV seroconversion upon enrolment into a prospective cohort study
      was strongly and independently associated with the subsequent rate of HIV
      seroconversion. Since this risk marker remained independently associated with HIV
      seroconversion, even after adjustment for time-updated risk behaviours, our
      findings have major implications that may aid outreach workers in their efforts
      to identify IDUs who should be targeted with prevention efforts.

PMID- 15561748
TI  - Parental pregnancy intention and early childhood stunting: findings from Bolivia.
AB  - BACKGROUND: This study examined the impact of maternally reported pregnancy
      intention, differentiating unwanted and mistimed pregnancies, on the prevalence
      of early childhood stunting. Additionally, it examined the influence of paternal
      pregnancy intention status. METHODS: Data were collected from a nationally
      representative sample of women and men interviewed in the 1998 Bolivia
      Demographic and Health Survey. The sample was restricted to lastborn, singleton
      children younger than 36 months who had complete anthropometric information.
      Multivariable logistic regression examined the association between pregnancy
      intention and stunting. RESULTS: Children from unwanted and mistimed pregnancies
      comprised 33% and 21% of the sample, respectively. Approximately 29% of the
      maternally unwanted children were stunted as compared to 19% among intended and
      19% among mistimed children. Children 12-35 months (toddlers) from mistimed
      pregnancies (adjusted prevalence risk ratio [PR(adj)] 1.33, 95% confidence
      interval [CI]: 1.03-1.72) and unwanted pregnancies (PR(adj) 1.28, 95% CI: 1.04
      1.56) were at about a 30% greater risk for stunting than children from intended
      pregnancies. Infants and toddlers with both parents reporting them as unwanted
      had an increased risk of being stunted as compared with children both of whose
      parents intended the pregnancy. No association was found for infants less than 12
      months. CONCLUSIONS: Reducing unintended pregnancies in Bolivia may decrease the
      prevalence of childhood growth stunting. Children born to parents reporting
      mistimed or unwanted pregnancies should be monitored for growth stunting, and
      appropriate interventions should be developed. Measurement of paternal pregnancy
      intention status is valuable in pregnancy intention studies.

PMID- 15561749
TI  - Evaluation of protective equipment for prevention of injuries in rugby union.
AB  - BACKGROUND: Rugby union has a high rate of injury. The increased use of
      protective equipment may help mitigate these injuries. This study investigated
      the injury prevention effectiveness of the protective equipment used in rugby
      union. METHODS: A cohort of 304 rugby players in Dunedin, New Zealand was
      followed weekly during the 1993 club season to assess protective equipment use,
      participation in rugby, and injury outcomes. Generalized Poisson regression was
      used to model the rate of injury while adjusting for covariates such as level of
      competition, playing position, and injury history. RESULTS: The use of
      mouthguards appeared to lower the risk of orofacial injury [rate ratio (RR) =
      0.56, 95% confidence interval (CI): 0.07-4.63], and padded headgear tended to
      prevent damage to the scalp and ears (RR = 0.59, 95% CI: 0.19-1.86). Support
      sleeves tended to reduce the risk of sprains and strains (RR = 0.58, 95% CI: 0.26
      1.27). The risk of concussion was not lessened by the use of padded headgear (RR
      = 1.13, 95% CI: 0.40-3.16) or mouthguards (RR = 1.62, 95% CI: 0.51-5.11). There
      was no evidence of protective effects for any other equipment item (taping,
      shinguards, and grease). CONCLUSIONS: The protective equipment used in rugby
      union has limited effectiveness in preventing injuries. The results are
      supportive, however, of a role for mouthguards and padded headgear in preventing
      orofacial and scalp injuries, respectively, and for support sleeves in preventing
      sprains and strains.

PMID- 15561750
TI  - The shape of the relationship between income and self-assessed health: an
      international study.
AB  - BACKGROUND: The relationship between income and health is usually thought to be
      curvilinear, but previous studies have yielded inconsistent results. We therefore
      examined the shape of the relationship between household equivalent income and
      self-assessed health in seven European countries. METHODS: Data were obtained
      from nationally representative health, level of living, or similar surveys in
      Belgium, Denmark, England, Finland, France, The Netherlands, and Norway and
      applied to men and women aged 25 years and older in the 1990s. Smooth
      nonparametric curves were fitted to the data, as well as a spline regression
      function with three linear pieces connected by two knots. RESULTS: A higher
      household equivalent income is associated with better self-assessed health among
      men and women in all countries, particularly in the middle-income range. In the
      higher income ranges, the relationship is generally curvilinear and characterized
      by less improvement in self-assessed health per unit of rising income. In the
      lowest income ranges, the relationship is found to be curvilinear in four
      countries (Belgium, Finland, The Netherlands, and Norway), where the usual
      deterioration of health associated with lower incomes levels off or even reverses
      into an improvement. CONCLUSIONS: Further research is necessary to investigate
      the background of differences between countries in the shape of the relationship
      between income and self-assessed health, and should focus on both methodological
      and substantive explanations. Assuming causality, the results of our study lend
      some support to the notion of decreasing marginal health returns of a unit
      increase in income at the higher income ranges.

PMID- 15561751
TI  - MORGAM (an international pooling of cardiovascular cohorts).

PMID- 15561752
TI  - Causes of death among human immunodeficiency virus (HIV)-infected adults in the
      era of potent antiretroviral therapy: emerging role of hepatitis and cancers,
      persistent role of AIDS.
AB  - BACKGROUND: In the era of highly active antiretroviral therapy (HAART) mortality
      has decreased substantially among human immunodeficiency virus (HIV)-infected
      people with access to HAART, but there are concerns regarding co-morbidities and
      adverse effects of HAART, which may impair vital prognosis. The Mortality 2000
      study examined the causes of death in HIV-infected adults at a national level in
      France in the year 2000. METHODS: All French hospital wards known to be involved
      in the management of HIV infection were asked to notify prospectively the deaths
      that occurred in 2000 among HIV-infected adults. The causes of death were
      documented using a standardized questionnaire. RESULTS: The 185 participating
      wards notified 964 deaths. The main underlying causes of death were AIDS-related
      (47%, non-Hodgkin's lymphoma: 23%), viral hepatitis (11%, hepatitis C: 9%,
      hepatitis B: 2%), cancer not related to AIDS or hepatitis (11%), cardiovascular
      disease (7%), bacterial infections (6%), suicide (4%), and adverse effect of
      antiretroviral treatments (1%). Among AIDS-related deaths, HIV infection had been
      diagnosed recently in 20%. Smoking was recorded in 72% of cancer-related deaths
      and alcohol consumption in 54% of hepatitis-related deaths. Among non-HIV related
      deaths between 25 and 64 years, the proportion of infectious diseases (including
      HCV and HBV-related deaths) was higher in HIV-infected adults than in the general
      population. CONCLUSIONS: Improved strategies for detecting HIV infection before
      AIDS-defining complications occur are needed in the era of HAART. The prevention
      of non-AIDS related cancers, especially lung cancer, the management of non
      Hodgkin's lymphoma, and of viral hepatitis are also important priorities.

PMID- 15561753
TI  - Investigating patient exclusion bias in meta-analysis.
AB  - BACKGROUND: Trial investigators frequently exclude patients from trial analyses
      which may bias estimates of the effect of treatment. Combining these estimates in
      a meta-analysis could aggregate any such biases. METHODS: To investigate how
      excluding patients from trials can affect the results of both trials and meta
      analyses, we used 14 meta-analyses of individual patient data (IPD) that
      addressed therapeutic questions in cancer. These included 133 randomized
      controlled trials (RCT) and 21 905 patients. We explored whether exclusions were
      related to trial characteristics and categorized the reasons for exclusions. For
      each RCT and meta-analysis, we compared results of an intention-to-treat analysis
      of all randomized patients with an analysis based on those patients included in
      the investigators' analysis. RESULTS: In all, 92 trials (69%) excluded between
      0.3 and 38% of patients randomized. Trials excluding patients tended to be older
      and larger than those that did not. Most patients were excluded because of
      ineligibility or protocol violations. Exclusions varied substantially by meta
      analysis, more patients tending to be excluded from the treatment arm. Comparing
      trial analyses there was no clear indication that exclusion of patients altered
      the results more in favour of either treatment or control. However, comparing
      meta-analysis results, there was a tendency for those based on 'included'
      patients to favour the research treatment (P = 0.03). Inconsistency of trial
      results was often increased as a result of the investigators' exclusions.
      CONCLUSIONS: Trials, systematic reviews, and meta-analyses may be prone to bias
      associated with post-randomization exclusion of patients. Wherever possible, the
      level of such exclusions should be taken into account when assessing the
      potential for bias in trials, systematic reviews, and meta-analyses. Ideally,
      trials, systematic reviews, and meta-analyses should be based on all randomized
      patients.

PMID- 15561754
TI  - Cause-specific mortality differences across socioeconomic position of
      municipalities in Japan, 1973-1977 and 1993-1998: increased importance of injury
      and suicide in inequality for ages under 75.
AB  - BACKGROUND: Socioeconomic inequality in health has been a major concern in public
      health. This study examined socioeconomic inequality in regional mortality and
      the impact on inequality by cause of deaths in 1973-1977 and 1993-1998 using
      municipal statistics in Japan. METHODS: The municipalities across the country (N
      = 3244 in 1973-1977 and 3334 in 1993-1998) were classified into quintiles
      according to the index of socioeconomic position (SEP) obtained by principal
      component analysis of municipal indicators related to income and education.
      Mortality gradient by SEP for selected major causes of death in the population
      aged 0-74 years was examined using standardized mortality ratio by quintile and
      rate ratio of mortality across quintiles. As a measure of cause-specific impact
      on inequality, the number of excess deaths from each cause in the lower four SEP
      quintiles compared with the highest quintile was calculated. RESULTS: Mortality
      gradient by SEP and excess deaths in the lower SEP quintiles due to injury and
      suicide markedly increased from 1973-1977 to 1993-1998 for both males and
      females. In contrast, stroke, especially cerebral haemorrhage, showed a decrease
      in mortality gradient and excess deaths. For females in 1993-1998, a negative
      gradient of mortality by SEP was found, and cancer contributed the higher all
      cause mortality in the higher SEP quintile. CONCLUSIONS: The relative importance
      of socioeconomic inequality in regional mortality of stroke decreased, while that
      of injury and suicide increased. The prevention of injury and suicide, in
      addition to stroke, in socioeconomically disadvantaged regions, and cancer in
      urban areas with higher SEP should be given priority.

PMID- 15561755
TI  - Benefits of routine immunizations on childhood survival in Tari, Southern
      Highlands Province, Papua New Guinea.
AB  - BACKGROUND: Non-specific beneficial as well as deleterious effects of childhood
      immunizations have been reported in areas of high mortality. This study aimed to
      determine the effects of diphtheria-tetanus-whole-cell-pertussis (DTP), BCG,
      hepatitis B, and measles vaccines on mortality in the highlands of Papua New
      Guinea (PNG). METHODS: Demographic events for children born in 1989-1994 who were
      under monthly demographic surveillance in Tari were recorded from birth until age
      2 years, out-migration, death, or the end of the study period. Data on BCG,
      hepatitis B, DTP, measles and pneumococcal polysaccharide vaccination were
      collected monthly from clinic records. To allow for different characteristics of
      immunized and non-immunized children, analysis included conditioning on a
      propensity score for vaccination, adjusting for differences in children's
      background characteristics. RESULTS: In all, 101/3502 children (3%) who had at
      least one vaccine died between ages 29 days and 24 months were compared to
      112/546 (21%) who had none. BCG was associated with lower mortality in the 1-5
      month age group (hazard ratio [HR] = 0.17, 95% CI: 0.09, 0.34), measles vaccine
      with lower mortality at age 6-11 months (HR = 0.42, 95% CI: 0.17, 1.01), and
      pneumococcal polysaccharide vaccine with lower mortality at age 12-23 months (HR
      = 0.42, 95% CI: 0.19, 0.93). One or more doses of DTP was associated with lower
      overall mortality (HR = 0.27, 95% CI: 0.16, 0.44), particularly in the 1-5 month
      age group (HR = 0.19, 95% CI: 0.10, 0.34), and also in those who had had prior
      BCG (HR = 0.45, 95% CI: 0.22, 0.91). CONCLUSION: Routine immunizations are
      effective in reducing overall mortality in young children in an area of high
      mortality. In particular, DTP, whether considered separately or in addition to
      BCG, was associated with a lowering of overall mortality, in contrast to findings
      reported from Guinea-Bissau.

PMID- 15561756
TI  - Impaired interleukin-8- and GROalpha-induced phosphorylation of extracellular
      signal-regulated kinase result in decreased migration of neutrophils from
      patients with myelodysplasia.
AB  - Patients with myelodysplasia suffer from recurrent bacterial infections as a
      result of differentiation defects of the myeloid lineage and a disturbed
      functioning of neutrophilic granulocytes. Important physiological activators of
      neutrophils are the cytokines interleukin-8/CXC chemokine ligand 8 (IL-8/CXCL8),
      which activates CXC chemokine receptor 1 and 2 (CXCR1 and CXCR2), and growth
      related oncogene (GROalpha)/CXCL1, which stimulates only CXCR2. In this study, we
      show that migration toward IL-8/GROalpha gradients is decreased in
      myelodysplastic syndrome (MDS) neutrophils compared with healthy donors. We
      investigated the signal transduction pathways involved in IL-8/GROalpha-induced
      migration and showed that specific inhibitors for extracellular signal-regulated
      kinase (ERK)1/2 and phosphatidylinositol-3 kinase (PI-3K) abrogated neutrophil
      migration toward IL-8/GROalpha. In accordance with these results, we subsequently
      showed that IL-8/GROalpha-stimulated activation of ERK1/2 was substantially
      diminished in MDS neutrophils. Activation of the PI-3K downstream target protein
      kinase B/Akt was disturbed in MDS neutrophils when cells were activated with IL-8
      but normal upon GROalpha stimulation. IL-8 stimulation resulted in higher
      migratory behavior and ERK1/2 activation than GROalpha stimulation, suggesting a
      greater importance of CXCR1. We then investigated IL-8-induced activation of the
      small GTPase Rac implicated in ERK1/2-dependent migration and found that it was
      less efficient in neutrophils from MDS patients compared with healthy donors. In
      contrast, IL-8 triggered a normal activation of the GTPases Ras and Ral,
      indicating that the observed defects were not a result of a general disturbance
      in CXCR1/2 signaling. In conclusion, our results demonstrate a disturbed CXCR1-
      and CXCR2-induced neutrophil chemotaxis in MDS patients, which might be the
      consequence of decreased Rac-ERK1/2 and PI-3K activation within these cells.

PMID- 15561757
TI  - Targeting brain stem centers of cardiovascular control using adenoviral vectors:
      impact of promoters on transgene expression.
AB  - Adenoviral vectors (AVV) are widely used as tools for exploring gene function in
      studies of the central autonomic control, but the cellular specificity of the
      promoters commonly used in these vectors has not been studied. We evaluated AVV
      with four "wide-spectrum" promoters, human cytomegalovirus promoter (HCMV),
      synapsin-1 promoter (Syn1), tubulin-alpha1 promoter (Talpha1), and neuron
      specific enolase (NSE) for their ability to express enhanced green fluorescent
      protein (EGFP) within the dorsal vagal complex and the adjacent brain stem. They
      were compared with the PRSx8 promoter, specifically designed to target
      catecholaminergic neurons. AdHCMVEGFP, AdSyn1EGFP-WHE (woodchuck hepatitis
      enhancer element), AdTalpha1EGFP, and AdNSEEGFP were unable to drive expression
      of EGFP in dopamine beta-hydroxylase-immunoreactive neurons of the A2 cell group,
      although the adjacent dorsal vagal motonucleus and especially hypoglossal
      motoneurons did express high levels of EGFP. AdPRSx8EGFP efficiently drove EGFP
      expression in the A2 cell group but also in choline acetyltransferase-positive
      vagal motoneurons. However, catecholaminergic neurons could be selectively and
      efficiently transduced via a retrograde route by injecting the vector into their
      target areas. Thus AVV with "wide-spectrum" promoters have strikingly different
      activity in the diverse cellular populations within brain stem cardiovascular
      control centers. The PRSx8 promoter is a valuable tool for the study of the role
      of catecholaminergic neurons.

PMID- 15561758
TI  - Sex-specific effects of dual ET-1/ANG II receptor (Dear) variants in Dahl salt
      sensitive/resistant hypertension rat model.
AB  - Essential (polygenic) hypertension is a complex genetic disorder that remains a
      major risk factor for cardiovascular disease despite clinical advances,
      reiterating the need to elucidate molecular genetic mechanisms. Elucidation of
      susceptibility genes remains a challenge, however. Blood pressure (BP) regulatory
      pathways through angiotensin II (ANG II) and endothelin-1 (ET-1) receptor systems
      comprise a priori candidate susceptibility pathways. Here we report that the dual
      ET-1/ANG II receptor gene (Dear) is structurally and functionally distinct
      between Dahl salt-sensitive, hypertensive (S) and salt-resistant, normotensive
      (R) rats. The Dahl S S44/M74 variant is identical to the previously reported Dear
      cDNA with equivalent affinities for both ET-1 and ANG II, in contrast to Dahl R
      S44P/M74T variant, which exhibits absent ANG II binding but effective ET-1
      binding. The S44P substitution localizes to the ANG II-binding domain predicted
      by the molecular recognition theory, providing compelling support of this theory.
      The Dear gene maps to rat chromosome 2 and cosegregates with BP in female F2(RxS)
      intercross rats with highly significant linkage (LOD 3.61) accounting for 14% of
      BP variance, but not in male F2(RxS) intercross rats. Altogether, the data
      suggest the hypothesis that modification of the critical balance between ANG II
      and ET-1 systems through variant Dear contributes to hypertension susceptibility
      in female F2(RxS) intercross rats. Further investigations are necessary to
      corroborate genetic linkage through congenic rat studies, to investigate putative
      gene interactions, and to show causality by transgenesis and/or intervention.
      More importantly, the data reiterate the importance of sex-specific factors in
      hypertension susceptibility.

PMID- 15561759
TI  - Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases.
AB  - Blood vessels and blood cells are under continuous fluid shear. Studies on
      vascular endothelium and smooth muscle cells have shown the importance of this
      mechanical stress in cell signal transduction, gene expression, vascular
      remodeling, and cell survival. However, in circulating leukocytes, shear-induced
      signal transduction has not been investigated. Here we examine in vivo and in
      vitro the control of pseudopods in leukocytes under the influence of fluid shear
      stress and the role of the Rho family small GTPases. We used a combination of HL
      60 cells differentiated into neutrophils (1.4% dimethyl sulfoxide for 5 days) and
      fresh leukocytes from Rac knockout mice. The cells responded to shear stress (5
      dyn/cm2) with retraction of pseudopods and reduction of their projected cell
      area. The Rac1 and Rac2 activities were decreased by fluid shear in a time- and
      magnitude-dependent manner, whereas the Cdc42 activity remained unchanged (up to
      5 dyn/cm2). The Rho activity was transiently increased and recovered to static
      levels after 10 min of shear exposure (5 dyn/cm2). Inhibition of either Rac1 or
      Rac2 slightly but significantly diminished the fluid shear response. Transfection
      with Rac1-positive mutant enhanced the pseudopod formation during shear.
      Leukocytes from Rac1-null and Rac2-null mice had an ability to form pseudopods in
      response to platelet-activating factor but did not respond to fluid shear in
      vitro. Leukocytes in wild-type mice retracted pseudopods after physiological
      shear exposure, whereas cells in Rac1-null mice showed no retraction during equal
      shear. On leukocytes from Rac2-null mice, however, fluid shear exerted a biphasic
      effect. Leukocytes with extended pseudopods slightly decreased in length, whereas
      initially round cells increased in length after shear application. The disruption
      of Rac activity made leukocytes nonresponsive to fluid shear, induced cell
      adhesion and microvascular stasis, and decreased microvascular density. These
      results suggest that deactivation of Rac activity by fluid shear plays an
      important role in stable circulation of leukocytes.

PMID- 15561760
TI  - Plasticity of TRPC expression in arterial smooth muscle: correlation with store
      operated Ca2+ entry.
AB  - Loss of the smooth muscle contractile phenotype is critical in atherosclerosis
      and in restenosis after angioplasty, but its early signals are incompletely
      understood. In this study, we have explored the role of transient receptor
      potential canonical (TRPC) proteins, which have been suggested to mediate store
      operated Ca2+ entry (SOCE). Contractility of rat cerebral arteries in organ
      culture is preserved for several days, whereas SOCE is increased. In correlation
      with this increase is that nifedipine-insensitive whole cell current, activated
      by depletion of intracellular Ca2+ stores, was increased by 50% in cells isolated
      from arteries cultured for 3 days. TRPC1 and TRPC6 mRNA were more than fivefold
      increased in cells isolated after organ culture, whereas TRPC3 was decreased.
      Immunofluorescent staining and/or Western blotting of arteries and isolated cells
      showed upregulation of TRPC1 and TRPC6 proteins during organ culture. In intact
      arteries, TRPC4 expression correlated with the amount of endothelium present.
      Ca2+ addition after store depletion caused a contraction in cultured, but not in
      freshly dissected, arteries. A polyclonal TRPC1 antibody directed against an
      extracellular epitope inhibited this contraction by approximately 50%. To
      investigate the basis of the TRPC upregulation and assess its possible clinical
      significance, segments of human internal mammary artery were organ cultured for
      24 h and then exposed to balloon dilatation in vitro, followed by further
      culturing for up to 48 h. After dilatation, TRPC1 and TRPC6 mRNA were
      progressively increased compared with undilated control segments. The results of
      this study indicate that vascular injury enhances plasticity in TRPC expression,
      that TRPC expression correlates with cellular Ca2+ handling, and that TRPC1 is a
      subunit of upregulated store-operated Ca2+ channels.

PMID- 15561761
TI  - Monocrotaline pyrrole-induced endothelial cell megalocytosis involves a Golgi
      blockade mechanism.
AB  - Pyrrolizidine alkaloids initiate disease in the lung (pulmonary hypertension),
      liver (veno-occlusive disease and cirrhosis), and kidneys (afferent arteriolar
      block and mesangiolysis) by inducing a megalocytotic phenotype in target
      endothelial and parenchymal cells. A "hit-and-run" type of exposure to the
      bioactive pyrrolizidine results, within 2-3 days, in enlarged cells with large
      nuclei and enlarged Golgi and endoplasmic reticulum, while the cells remain in
      G2/M block. In the present study, we recapitulated monocrotaline pyrrole (MCTP)
      induced megalocytosis in cultures of bovine pulmonary arterial endothelial cells
      (PAEC), human Hep3B hepatocytes, human type II-like alveolar epithelial cells
      (A549), and human pulmonary arterial smooth muscle cells (PASMC) and investigated
      the subcellular mechanism involved. There was an inverse relationship between
      reduction in caveolin (Cav)-1 levels and stimulation of promitogenic STAT3 and
      ERK1/2 cell signaling. In megalocytotic PAEC, the Golgi scaffolding protein GM130
      was shifted from membranes with heavy density to those with a lighter density.
      This lighter Golgi fraction was enriched for hypo-oligomeric Cav-1, indicating
      dysfunctional trafficking of cargo. Immunofluorescence imaging studies confirmed
      the trapping of Cav-1 in a GM130-positive Golgi compartment. There was an
      increase in Ser25 phosphorylation of GM130 (typically a prelude to Golgi
      fragmentation and mitosis) and increased association between pGM130, cdc2 kinase,
      and Cav-1. Nevertheless, megalocytotic MCTP-treated cells showed reduced entry
      into mitosis upon stimulation with 2-methoxyestradiol (2-ME), reduced 2-ME
      induced Golgi fragmentation, and a slowing of Golgi reassembly after nocodazole
      induced fragmentation. These data suggest that a disruption of the trafficking
      and mitosis sensor functions of the Golgi may represent the subcellular mechanism
      leading to MCTP-induced megalocytosis ("the Golgi blockade hypothesis").

PMID- 15561762
TI  - Nitric oxide-induced persistent inhibition and nitrosylation of active site
      cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial
      cells.
AB  - Persistent inhibition of cytochrome-c oxidase, a terminal enzyme of the
      mitochondrial electron transport chain, by excessive nitric oxide (NO) derived
      from inflammation, polluted air, and tobacco smoke contributes to enhanced
      oxidant production and programmed cell death or apoptosis of lung cells. We
      sought to determine whether the long-term exposure of pulmonary artery
      endothelial cells (PAEC) to pathophysiological concentrations of NO causes
      persistent inhibition of complex IV through redox modification of its key
      cysteine residues located in a putative NO-sensitive motif. Prolonged exposure of
      porcine PAEC to 1 mM 2,2'-(hydroxynitrosohydrazino)-bis-ethanamine (NOC-18; slow
      releasing NO donor, equivalent to 1-5 microM NO) resulted in a gradual,
      persistent inhibition of complex IV concomitant with a reduction in ratios of
      mitochondrial GSH and GSSG. Overexpression of thioredoxin in mitochondria of PAEC
      attenuated NO-induced loss of complex IV activities, suggesting redox regulation
      of complex IV activity. Sequence analysis of complex IV subunits revealed a novel
      putative NO-sensitive motif in subunit II (S2). There are only two cysteine
      residues in porcine complex IV S2, located in the putative motif.
      Immunoprecipitation and Western blot analysis and "biotin switch" assay
      demonstrated that exposure of PAEC to 1 mM NOC-18 increased S-nitrosylation of
      complex IV S2 by 200%. Site-directed mutagenesis of these two cysteines of
      complex IV S2 attenuated NO-increased nitrosylation of complex IV S2. These
      results demonstrate for the first time that NO nitrosylates active site cysteines
      of complex IV, which is associated with persistent inhibition of complex IV. NO
      inhibition of complex IV via nitrosylation of NO-sensitive cysteine residues can
      be a novel upstream event in NO-complex IV signaling for NO toxicity in lung
      endothelial cells.

PMID- 15561763
TI  - Analysis of the LKB1-STRAD-MO25 complex.
AB  - Mutations in the LKB1 tumour suppressor threonine kinase cause the inherited
      Peutz-Jeghers cancer syndrome and are also observed in some sporadic cancers.
      Recent work indicates that LKB1 exerts effects on metabolism, polarity and
      proliferation by phosphorylating and activating protein kinases belonging to the
      AMPK subfamily. In vivo, LKB1 forms a complex with STRAD, an inactive
      pseudokinase, and MO25, an armadillo repeat scaffolding-like protein. Binding of
      LKB1 to STRAD-MO25 activates LKB1 and re-localises it from the nucleus to the
      cytoplasm. To learn more about the inherent properties of the LKB1-STRAD-MO25
      complex, we first investigated the activity of 34 point mutants of LKB1 found in
      human cancers and their ability to interact with STRAD and MO25. Interestingly,
      12 of these mutants failed to interact with STRAD-MO25. Performing mutagenesis
      analysis, we defined two binding sites located on opposite surfaces of MO25alpha,
      which are required for the assembly of MO25alpha into a complex with STRADalpha
      and LKB1. In addition, we demonstrate that LKB1 does not require phosphorylation
      of its own T-loop to be activated by STRADalpha-MO25alpha, and discuss the
      possibility that this unusual mechanism of regulation arises from LKB1
      functioning as an upstream kinase. Finally, we establish that STRADalpha, despite
      being catalytically inactive, is still capable of binding ATP with high affinity,
      but that this is not required for activation of LKB1. Taken together, our
      findings reinforce the functional importance of the binding of LKB1 to STRAD, and
      provide a greater understanding of the mechanism by which LKB1 is regulated and
      activated through its interaction with STRAD and MO25.

PMID- 15561764
TI  - Multiple mechanisms regulate NuMA dynamics at spindle poles.
AB  - The large coiled-coil protein NuMA plays an essential role in organizing
      microtubule minus ends at spindle poles in vertebrate cells. Here, we use both in
      vivo and in vitro methods to examine NuMA dynamics at mitotic spindle poles.
      Using fluorescence recovery after photobleaching, we show that an exogenously
      expressed green-fluorescent-protein/NuMA fusion undergoes continuous exchange
      between soluble and spindle-associated pools in living cells. These dynamics
      require cellular energy and display an average half-time for fluorescence
      recovery of approximately 3 minutes. To explore how NuMA dynamics at spindle
      poles is regulated, we exploited the association of NuMA with microtubule asters
      formed in mammalian mitotic extracts. Using a monoclonal antibody specific for
      human NuMA, we followed the fate of human NuMA associated with microtubule asters
      upon dilution with a hamster mitotic extract. Consistent with in vivo data, this
      assay shows that NuMA can be displaced from the core of pre-assembled asters into
      the soluble pool. The half-time of NuMA displacement from asters under these
      conditions is approximately 5 minutes. Using this assay, we show that protein
      kinase activity and the NuMA-binding protein LGN regulate the dynamic exchange of
      NuMA on microtubule asters. Thus, the dynamic properties of NuMA are regulated by
      multiple mechanisms including protein phosphorylation and binding to the LGN
      protein, and the rate of exchange between soluble and microtubule-associated
      pools suggests that NuMA associates with an insoluble matrix at spindle poles.

PMID- 15561765
TI  - Degradation of APCcdc20 and APCcdh1 substrates during the second meiotic division
      in mouse eggs.
AB  - Metaphase II-arrested mouse eggs are stimulated to complete meiosis by sperm
      induced Ca2+ spiking. The Ca2+ signal causes activation of the E3 ligase anaphase
      promoting complex/cyclosome (APC), leading to the destruction of key proteins
      necessary for meiotic exit. We show, using western blots of mouse eggs, the
      presence of both APC activators cdc20 and cdh1, which target D-box and D-box/KEN
      box substrates, respectively, for proteolysis. We decided to examine the temporal
      activation of APCcdc20 and APCcdh1 by coupling APC substrates to GFP and
      examining their destruction in real-time following release from second meiotic
      division arrest. D-box substrates were degraded quickly after the initiation of
      sperm-induced Ca2+ spiking, such that their degradation was complete by the time
      of second polar body extrusion. By contrast, KEN-box-containing substrates were
      degraded when CDK1 activity was low, during the period between polar body
      extrusion and pronucleus formation. This observation of apparent APCcdh1 activity
      in meiosis II based on destruction of exogenous GFP-coupled substrates was then
      confirmed by observing destruction of endogenous APCcdh1 substrates. These data
      are consistent with a model of initial APCcdc20 activation on sperm-induced
      activation, followed by APCcdh1 activation after second polar body extrusion.
      Interestingly, therefore, we propose that mammalian eggs undergo meiosis II with
      both APCcdc20 and APCcdh1, whereas eggs of other species so far described have
      APCcdc20 activity only.

PMID- 15561766
TI  - TNFalpha induces sequential activation of Cdc42- and p38/p53-dependent pathways
      that antagonistically regulate filopodia formation.
AB  - Cell migration is an essential function in various physiological processes,
      including tissue repair and tumour invasion. Repair of tissue damage requires the
      recruitment of fibroblasts to sites of tissue injury, which is mediated in part
      by the cytokine tumour necrosis factor alpha (TNFalpha). As dynamic
      rearrangements of actin cytoskeleton control cell locomotion, this implicates
      that TNFalpha is a potent coordinator of cellular actin changes. We have
      investigated the role of TNFalpha in regulating the cortical actin-containing
      structures essential for cell locomotion called filopodia. Kinetic analysis of
      TNFalpha-treated mouse embryonic fibroblasts (MEFs) revealed a dual effect on
      filopodia formation: a rapid and transient induction mediated by Cdc42 GTPase
      that is then counteracted by a subsequent sustained inhibition requiring
      activation of the mitogen-activated protein kinase p38 but not Cdc42 activity.
      This inhibition also involves the tumour suppressor p53, given that it is
      activated in response to TNFalpha following the same time course as the decrease
      of filopodia formation. This functional activation of p53, measured by
      transcription induction of its target p21WAF1(p21), is also associated with p38
      kinase-dependent phosphorylation of p53 at serine 18. Furthermore, TNFalpha did
      not inhibit filopodia formation in MEFs treated with the transcription inhibitor
      actinomycin D, in p53-deficient MEFs, or MEFs expressing p53 mutants H273 or
      H175, which supports a role for the transcriptional activity of p53 in mediating
      TNFalpha-dependent filopodia inhibition. Our data delineate a novel inhibitory
      pathway in which TNFalpha prevents filopodia formation and cell migration through
      the activation of the mitogen-activated protein kinase (MAPK) p38, which in turn
      activates p53. This shows that TNFalpha on its own initiates antagonistic signals
      that modulate events linked to cell migration.

PMID- 15561767
TI  - AtRabF2b (Ara7) acts on the vacuolar trafficking pathway in tobacco leaf
      epidermal cells.
AB  - Rab GTPases are universal key regulators of intracellular secretory trafficking
      events. In particular, Rab 5 homologues have been implicated in endocytic events
      and in the vacuolar pathway. In this study, we investigate the location and
      function of a member of this family, AtRabF2b (Ara7) in tobacco (Nicotiana
      tabacum) leaf epidermal cells using a live cell imaging approach. Fluorescent
      tagged AtRabF2b[wt] localized to the prevacuolar compartment and Golgi apparatus,
      as determined by coexpression studies with fluorescent markers for these
      compartments. Mutations that impair AtRabF2b function also alter the subcellular
      location of the GTPase. In addition, coexpression studies of the protein with the
      vacuole-targeted aleurain-green fluorescent protein (GFP) and rescue experiments
      with wild-type AtRabF2b indicate that the dominant-negative mutant of AtRabF2b
      causes the vacuolar marker to be secreted to the apoplast. Our results indicate a
      clear role of AtRabF2b in the vacuolar trafficking pathway.

PMID- 15561768
TI  - Intracellular processing and activation of membrane type 1 matrix metalloprotease
      depends on its partitioning into lipid domains.
AB  - The integral membrane type 1 matrix metalloprotease (MT1-MMP) is a pivotal
      protease in a number of physiological and pathological processes and confers both
      non-tumorigenic and tumorigenic cell lines with a specific growth advantage in a
      three-dimensional matrix. Here we show that, in a melanoma cell line, the
      majority (80%) of MT1-MMP is sorted to detergent-resistant membrane fractions;
      however, it is only the detergent-soluble fraction (20%) of MT1-MMP that
      undergoes intracellular processing to the mature form. Also, this processed MT1
      MMP is the sole form responsible for ECM degradation in vitro. Finally, furin
      dependent processing of MT1-MMP is shown to occur intracellularly after exit from
      the Golgi apparatus and prior to its arrival at the plasma membrane. It is thus
      proposed that the association of MT1-MMP with different membrane subdomains might
      be crucial in the control of its different activities: for instance in cell
      migration and invasion and other less defined ones such as MT1-MMP-dependent
      signaling pathways.

PMID- 15561769
TI  - Sorting nexin 5 is localized to a subdomain of the early endosomes and is
      recruited to the plasma membrane following EGF stimulation.
AB  - Sorting nexins are a large family of proteins that contain the phosphoinositide
      binding Phox homology (PX) domain. A number of sorting nexins are known to bind
      to PtdIns3P, which mediates their localization to membranes of the endocytic
      pathway. We show here that sorting nexin 5 (SNX5) can be recruited to two
      distinct membrane compartments. In non-stimulated cells, the PX domain was
      independently targeted to endosomal structures and colocalized with full-length
      SNX5. The membrane binding of the PX domain was inhibited by the PI 3-kinase
      inhibitor, wortmannin. Although SNX5 colocalized with a fluid-phase marker and
      was found predominantly within a PtdIns3P-rich endosomal domain, very little
      colocalization was observed between SNX5 and the PtdIns3P-binding protein, EEA1.
      Using liposome-based binding assays, we have shown that the PX domain of SNX5
      interacts not only with PtdIns3P but also with PtdIns3,4P2. In response to EGF
      stimulation, either the SNX5-PX domain or full-length SNX5 was rapidly recruited
      to the plasma membrane. The localization of SNX1, which does not bind
      PtdIns3,4P2, was unaffected by EGF signalling. Therefore, SNX5 is localized to a
      subdomain of the early endosome distinct from EEA1 and, following EGF stimulation
      and elevation of PtdIns3,4P2, is also transiently recruited to the plasma
      membrane. These results indicate that SNX5 may have functions not only associated
      with endosomal sorting but also with the phosphoinositide-signalling pathway.

PMID- 15561770
TI  - A role for the small GTPase Rab21 in the early endocytic pathway.
AB  - Rab proteins comprise a family of monomeric GTPases that control cellular
      membrane traffic. Rab21 is a poorly characterised member with no known function.
      Human Rab21 cDNA from K562 cells was subcloned into GFP expression vectors to
      generate Rab21 and Rab21 mutants defective in either GTP hydrolysis (Rab21 Q78L)
      or binding (Rab21 T33N) for transfection studies in HeLa cells. Confocal
      fluorescence microscopy and ultrastructural studies revealed Rab21 to be
      predominantly localised to the early endocytic pathway, on vesicles containing
      earlyendosomal antigen 1 EEA1, transferrin receptor and internalised ligands.
      EEA1 was localised to enlarged endosomes in Rab21 wild-type expressing cells but
      the GTP hydrolysis and GDP binding mutants had unique phenotypes labelling
      tubular reticular structures and the trans-Golgi network, respectively. Early
      endosome localisation for Rab21 was confirmed in a hepatoma cell line that
      allowed analysis of the subcellular distribution of the endogenous protein.
      Comparison of the localisation of Rab21 with other Rabs revealed extensive
      colocalisation with early endocytic variants Rab4, Rab5, Rab17 and Rab22 but much
      less overlap with those associated with late endosomes, recycling endosomes and
      the early secretory pathway. Cells expressing Rab21 T33N had defects in
      endocytosis of transferrin and epidermal growth factor and failed to effectively
      deliver the latter ligand to late endosomes and lysosomes for degradation.
      Collectively, our data provide the first characterisation of Rab21 function in
      early endosome dynamics.

PMID- 15561771
TI  - The spatial pattern of atrial cardiomyocyte calcium signalling modulates
      contraction.
AB  - We examined the regulation of calcium signalling in atrial cardiomyocytes during
      excitation-contraction coupling, and how changes in the distribution of calcium
      impacts on contractility. Under control conditions, calcium transients originated
      in subsarcolemmal locations and showed local regeneration through activation of
      calcium-induced calcium release from ryanodine receptors. Despite functional
      ryanodine receptors being expressed at regular (approximately 2 microm) intervals
      throughout atrial myocytes, the subsarcolemmal calcium signal did not spread in a
      fully regenerative manner through the interior of a cell. Rather, there was a
      diminishing centripetal propagation of calcium. The lack of regeneration was due
      to mitochondria and SERCA pumps preventing the inward movement of calcium.
      Inhibiting these calcium buffering mechanisms allowed the globalisation of action
      potential-evoked responses. In addition, physiological positive inotropic agents,
      such as endothelin-1 and beta-adrenergic agonists, as well as enhanced calcium
      current, calcium store loading and inositol 1,4,5-trisphosphate infusion also led
      to regenerative global responses. The consequence of globalising calcium signals
      was a significant increase in cellular contraction. These data indicate how
      calcium signals and their consequences are determined by the interplay of
      multiple subcellular calcium management systems.

PMID- 15561772
TI  - Truncating APC mutations have dominant effects on proliferation, spindle
      checkpoint control, survival and chromosome stability.
AB  - The majority of human tumour cells are aneuploid owing to an underlying
      chromosome instability phenotype. While the genetic lesions that cause chromosome
      instability remain undefined, mouse ES cells harbouring homozygous adenomatous
      polyposis coli (APC) mutations are frequently tetraploid. In addition, colon
      cancer cells with APC mutations have weakened kinetochore-microtubule
      interactions. Furthermore, mitotic spindles assembled in APC-depleted Xenopus egg
      extracts are aberrant. Therefore, to determine whether APC mutations can initiate
      chromosome instability in human cells, we expressed N-terminal APC fragments in
      HCT-116 cells, a near diploid colon cancer cell line with two wild-type APC
      alleles. We show that cells expressing N-APC mutants exit mitosis prematurely in
      the presence of spindle toxins, consistent with a spindle checkpoint defect. In
      addition, N-APC cells show enhanced survival following prolonged spindle damage.
      In contrast to controls, the N-APC survivors frequently contain dicentric
      chromosomes and then go on to become highly aneuploid. These observations suggest
      that truncating APC mutations can exert dominant effects which in turn can
      initiate chromosome instability. As such, APC mutation not only compromises
      tumour suppressor function but may also have oncogenic properties. We suggest
      therefore that the initial APC mutation acts as a 'double whammy', destabilising
      the genome and setting the stage for deregulated proliferation upon loss of the
      second APC allele.

PMID- 15561773
TI  - Function of Rho GTPases in embryonic blood cell migration in Drosophila.
AB  - Hemocyte development in the Drosophila embryo is a genetic model to study blood
      cell differentiation, cell migration and phagocytosis. Macrophages, which make up
      the majority of embryonic hemocytes, migrate extensively as individual cells on
      basement membrane-covered surfaces. The molecular mechanisms that contribute to
      this migration process are currently not well understood. We report the
      generation, by P element replacement, of two Gal4 lines that drive expression of
      UAS-controlled target genes during early (gcm-Gal4) or late (Coll-Gal4) stages of
      macrophage migration. gcm-Gal4 is used for live imaging analysis showing that
      macrophages extend large, dynamic lamellipodia as their main protrusions as well
      as filopodia. We use both Gal4 lines to express dominantnegative and
      constitutively active isoforms of the Rho GTPases Rac1, Cdc42, Rho1 and RhoL in
      macrophages, and complement these experiments by analyzing embryos mutant for Rho
      GTPases. Our findings suggest that Rac1 and Rac2 act redundantly in controlling
      migration and lamellipodia formation in Drosophila macrophages, and that the
      third Drosophila Rac gene, Mtl, makes no significant contribution to macrophage
      migration. Cdc42 appears not to be required within macrophages but in other
      tissues of the embryo to guide macrophages to the ventral trunk region. No
      evidence was found for a requirement of Rho1 or RhoL in macrophage migration.
      Finally, to estimate the number of genes whose zygotic expression is required for
      macrophage migration we analyzed 208 chromosomal deletions that cover most of the
      Drosophila genome. We find eight deletions that cause defects in macrophage
      migration suggesting the existence of approximately ten zygotic genes essential
      for macrophage migration.

PMID- 15561774
TI  - Multiple regions contribute to membrane targeting of Rab GTPases.
AB  - Small GTPases of the Rab family are key regulators of membrane trafficking. Each
      Rab shows a characteristic subcellular distribution, and may serve as an
      important determinant of organelle identity. The molecular mechanisms responsible
      for targeting Rabs to specific intracellular compartments, however, remain poorly
      understood. The divergent C-terminal hypervariable region was postulated to
      contain Rab targeting information. We generated a series of hybrid Rab proteins
      by exchanging the hypervariable domains of Rab1a, Rab2a, Rab5a, Rab7 and Rab27a,
      and analysed their subcellular localisations. We found that the various hybrid
      proteins retained their targeting to the parent organelle and were functionally
      active. We conclude that the hypervariable region does not contain a general Rab
      targeting signal. Furthermore, we identified other regions within the RabF and
      RabSF motifs that are required for specific targeting of Rab27a to secretory
      granules or melanosomes, and Rab5a to endosomes. We observed only partial overlap
      between targeting-determining regions in the Rab proteins examined, suggesting
      that Rab recruitment may be complex and at least partially Rab-specific.
      Mutations in these targeting-determining regions induced localisation to the ER,
      an observation that further strengthens our previous finding that ER/Golgi
      membranes serve as the default location for Rabs that have lost targeting
      information.

PMID- 15561775
TI  - SRK2C, a SNF1-related protein kinase 2, improves drought tolerance by controlling
      stress-responsive gene expression in Arabidopsis thaliana.
AB  - Protein phosphorylation/dephosphorylation are major signaling events induced by
      osmotic stress in higher plants. Here, we showed that a SNF1-related protein
      kinase 2 (SnRK2), SRK2C, is an osmotic-stress-activated protein kinase in
      Arabidopsis thaliana that can significantly impact drought tolerance of
      Arabidopsis plants. Knockout mutants of SRK2C exhibited drought hypersensitivity
      in their roots, suggesting that SRK2C is a positive regulator of drought
      tolerance in Arabidopsis roots. Additionally, transgenic plants with CaMV35S
      promoter::SRK2C-GFP displayed higher overall drought tolerance than control
      plants. Whereas stomatal regulation in 35S::SRK2C-GFP plants was not altered,
      microarray analysis revealed that their drought tolerance coincided with up
      regulation of many stress-responsive genes, for example, RD29A, COR15A, and
      DREB1A/CBF3. From these results, we concluded that SRK2C is capable of mediating
      signals initiated during drought stress, resulting in appropriate gene
      expression. Our present study reveals new insights around signal output from
      osmotic-stress-activated SnRK2 protein kinase as well as supporting feasibility
      of manipulating SnRK2 toward improving plant osmotic-stress tolerance.

PMID- 15561776
TI  - SRC regulates actin dynamics and invasion of malignant glial cells in three
      dimensions.
AB  - Malignant glioma is the major brain tumor in adults and has a poor prognosis. The
      failure to control invasive cell subpopulations may be the key reason for local
      glioma recurrence after radical tumor resection and may contribute substantially
      to the failure of the other treatment modalities such as radiation therapy and
      chemotherapy. As a model for this invasion, we have implanted spheroids from a
      human glioma cell line (U251) in three-dimensional collagen type I matrices,
      which these cells readily invade. We first observed that the Src family kinase
      specific pharmacologic inhibitors PP2 and SU6656 significantly inhibited the
      invasion of the cells in this assay. We confirmed this result by showing that
      expression of two inhibitors of Src family function, dominant-negative-Src and
      CSK, also suppressed glioma cell invasion. To characterize this effect at the
      level of the cytoskeleton, we used fluorescent time-lapse microscopy on U251
      cells stably expressing a YFP-actin construct and observed a rapid change in
      actin dynamics following addition of PP2 in both two-dimensional and three
      dimensional cultures. In monolayer cultures, PP2 caused the disappearance of
      peripheral membrane ruffles within minutes. In three-dimensional cultures, PP2
      induced the loss of actin bursting at the leading tip of the invadopodium. The
      inhibition of Src family activity is thus a potential therapeutic approach to
      treat highly invasive malignant glioma.

PMID- 15561777
TI  - HER-2/neu overexpression increases the viable hypoxic cell population within
      solid tumors without causing changes in tumor vascularization.
AB  - The effects of HER-2/neu overexpression on the tumor microenvironment in an
      aggressive breast cancer xenograft model were investigated. These studies focused
      on tumors derived following the subcutaneous injection of MDA-MB-435/LCC6 cells
      transfected with human c-erbB2 (LCC6(HER-2)) into SCID-Rag2M mice. LCC6(HER-2)
      tumors were more viable (H&E-stained tumor sections) than isogenic vector control
      tumors (LCC6(Vector)). Correspondingly, a 2.7-fold increase in trypan blue
      excluding cells (P = 0.00056) and a 4.8-fold increase in clonogenic cells (P =
      0.00146) were noted in cell suspensions derived from disaggregated LCC6(HER-2)
      versus LCC6(Vector) tumors. Tumor sections stained with the antibody detecting 2
      (2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5), a
      marker of hypoxia, showed a greater fraction of hypoxic tissue in LCC6(HER-2)
      tumors compared with control tumors. Flow cytometric analyses based on viable
      tumor cells (DNA content >/= 2N) in cell suspensions from disaggregated tumors
      confirmed that there were significantly more EF5-positive cells (i.e., hypoxic)
      in LCC6(HER-2) than in LCC6(Vector) tumors (16.41 +/- 8.1% and 5.96 +/- 4.1%,
      respectively; P = 0.0015). Protein levels of phosphorylated (Ser(536)) nuclear
      factor-kappaB p65 were significantly elevated in LCC6(HER-2) tumors (P =
      0.00048), and a trend in increased hypoxia-inducible factor-1alpha protein levels
      was observed in LCC6(HER-2) compared with LCC6(Vector) tumors. Despite the
      substantial viable hypoxic cell fraction and a 1.7-fold increase of vascular
      endothelial growth factor protein (P = 0.05) in LCC6(HER-2) tumors, no
      significant differences were found (P > 0.05) between LCC6(HER-2) and
      LCC6(Vector) vasculature (CD31 staining and Hoechst 33342 perfusion). These
      results suggest that HER-2/neu overexpression may be linked with overall
      increased tumor viability and a significant increase in the population of viable
      hypoxic cells, which is not due to differences in tumor vascularization.

PMID- 15561778
TI  - Bcl-2 overexpression leads to increases in suppressor of cytokine signaling-3
      expression in B cells and de novo follicular lymphoma.
AB  - The t(14;18)(q32;q21), resulting in deregulated expression of B-cell
      leukemia/lymphoma-2 (Bcl-2), represents the genetic hallmark in human follicular
      lymphomas. Substantial evidence supports the hypothesis that the t(14;18) and Bcl
      2 overexpression are necessary but not solely responsible for neoplastic
      transformation and require cooperating genetic derangements for neoplastic
      transformation to occur. To investigate genes that cooperate with Bcl-2 to
      influence cellular signaling pathways important for neoplastic transformation, we
      used oligonucleotide microarrays to determine differential gene expression
      patterns in CD19+ B cells isolated from Emu-Bcl-2 transgenic mice and wild-type
      littermate control mice. Fifty-seven genes were induced and 94 genes were
      repressed by > or =2-fold in Emu-Bcl-2 transgenic mice (P < 0.05). The suppressor
      of cytokine signaling-3 (SOCS3) gene was found to be overexpressed 5-fold in B
      cells from Emu-Bcl-2 transgenic mice. Overexpression of Bcl-2 in both mouse
      embryo fibroblast-1 and hematopoietic cell lines resulted in induction of SOCS3
      protein, suggesting a Bcl-2-associated mechanism underlying SOCS3 induction.
      Immunohistochemistry with SOCS3 antisera on tissue from a cohort of patients with
      de novo follicular lymphoma revealed marked overexpression of SOCS3 protein that,
      within the follicular center cell region, was limited to neoplastic follicular
      lymphoma cells and colocalized with Bcl-2 expression in 9 of 12 de novo
      follicular lymphoma cases examined. In contrast, SOCS3 protein expression was not
      detected in the follicular center cell region of benign hyperplastic tonsil
      tissue. These data suggest that Bcl-2 overexpression leads to the induction of
      activated signal transducer and activator of transcription 3 (STAT3) and to the
      induction of SOCS3, which may contribute to the pathogenesis of follicular
      lymphoma.

PMID- 15561779
TI  - Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo
      model of spontaneous metastatic breast cancer.
AB  - Cyclooxygenase-2 (COX-2) inhibitors are rapidly emerging as a new generation of
      therapeutic drug in combination with chemotherapy or radiation therapy for the
      treatment of cancer. The mechanisms underlying its antitumor effects are not
      fully understood and more thorough preclinical trials are needed to determine if
      COX-2 inhibition represents a useful approach for prevention and/or treatment of
      breast cancer. The purpose of this study was to evaluate the growth inhibitory
      mechanism of a highly selective COX-2 inhibitor, celecoxib, in an in vivo
      oncogenic mouse model of spontaneous breast cancer that resembles human disease.
      The oncogenic mice carry the polyoma middle T antigen driven by the mouse mammary
      tumor virus promoter and develop primary adenocarcinomas of the breast. Results
      show that oral administration of celecoxib caused significant reduction in
      mammary tumor burden associated with increased tumor cell apoptosis and decreased
      proliferation in vivo. In vivo apoptosis correlated with significant decrease in
      activation of protein kinase B/Akt, a cell survival signaling kinase, with
      increased expression of the proapoptotic protein Bax and decreased expression of
      the antiapoptotic protein Bcl-2. In addition, celecoxib treatment reduced levels
      of proangiogenic factor (vascular endothelial growth factor), suggesting a role
      of celecoxib in suppression of angiogenesis in this model. Results from these
      preclinical studies will form the basis for assessing the feasibility of
      celecoxib therapy alone or in combination with conventional therapies for
      treatment and/or prevention of breast cancer.

PMID- 15561780
TI  - Transforming potential of alternatively spliced variants of fibroblast growth
      factor receptor 2 in human mammary epithelial cells.
AB  - A breast cancer cell line developed in our laboratory (SUM-52PE) has a 12-fold
      amplification and high-level overexpression of the oncogene fibroblast growth
      factor receptor 2 (FGFR2). Previously, nine different alternatively spliced FGFR2
      variants were isolated from this cell line. Overexpression of two variants that
      differ only in their carboxyl termini (C1 and C3) has been successfully
      accomplished in the immortalized human mammary epithelial cell line H16N2. FGFR2
      expression led to the activation of the mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase signaling cascades. Phosphorylation of the adapter
      protein FGF receptor substrate 2 is much more robust in the cells expressing the
      C3 variant of FGFR2 compared with the C1 variant. H16N2 cells expressing the full
      length FGFR2 with the C1 or C3 carboxyl terminus were tested for their ability to
      grow under epidermal growth factor (EGF)-independent conditions, in soft agar,
      and for their ability to invade naturally occurring basement membranes and
      compared with the parental SUM-52PE cell line. All three cell lines grew under
      EGF-independent conditions and all were inhibited by the FGFR family specific
      inhibitor PD173074. The full-length FGFR2-C1 and FGFR2-C3 variants grew robustly
      in soft agar similar to the parental cell line SUM-52PE. However, cells
      expressing the C3 variant formed large colonies in agar in both insulin-free and
      EGF-free medium, whereas the cells expressing the C1 variant required insulin for
      growth. Soft agar growth was also inhibited by PD173074. Because SUM-52PE was
      developed from a metastatic breast carcinoma, the FGFR2-overexpressing cell lines
      were assessed for their ability to invade sea urchin embryo cell membranes. H16N2
      cells expressing the C1 carboxyl terminus failed to invade sea urchin embryo cell
      membranes. By contrast, FGFR2-C3-expressing cells were as invasive as the SUM-52
      breast cancer cells and erbB-2-overexpressing H16N2 cells. These results indicate
      that FGFR2 is a transforming oncogene in human mammary epithelial cells when
      expressed to levels similar to that found in breast cancer cells with FGFR2 gene
      amplification. Furthermore, the results suggest that different splice variants
      have differing transforming activities and that signaling from variants
      expressing the C3 carboxyl terminus results in more autonomous signaling, cell
      growth, and invasion.

PMID- 15561781
TI  - Exogenous fibroblast growth factors maintain viability, promote proliferation,
      and suppress GADD45alpha and GAS6 transcript content of prostate cancer cells
      genetically modified to lack endogenous FGF-2.
AB  - Understanding processes regulating prostate cancer cell survival is critical to
      management of advanced disease. We used prostate cancer cell transfectants
      genetically modified to be deficient in either endogenous fibroblast growth
      factor (FGF-1) or endogenous FGF-2 to examine FGF maintenance of transfectant
      survival and proliferation and FGF-2-regulated expression of transfectant growth
      arrest DNA damage (GADD) and growth arrest sequences (GAS) family genes (known
      modulators of cell cycle progression and survival) and the AS3 gene (an androgen
      modulated effector of prostate cell proliferation). When propagated in the
      absence of exogenous FGFs, FGF-2-deficient transfectants undergo exponential
      death, whereas FGF-1-deficient transfectants proliferate. Exogenous FGF-1, FGF-2,
      FGF-7, or FGF-8 promote survival and proliferation of FGF-2-deficient
      transfectants and enhance FGF-1-deficient transfectant proliferation.
      Transfectants express FGF receptor FGFR1, FGFR2(IIIb), FGFR2(IIIc), and FGFR3
      transcripts, findings consistent with the effects of exogenous FGFs. FGF-2
      deficient transfectants express high levels of AS3, GADD45alpha, GADD45gamma,
      GAS8, and GAS11 transcripts and moderate levels of GADD153, GAS2, GAS3, and GAS6
      transcripts and lack demonstrable GAS1 or GAS5 transcripts. FGF withdrawal
      mediated death of FGF-2-deficient transfectants did not significantly affect cell
      AS3, GADD153, GADD45gamma, GAS2, GAS3, GAS7, GAS8, or GAS11 transcript content,
      whereas GADD45alpha and GAS6 transcript content was elevated. These studies
      establish that endogenous FGF-2 dominantly regulates prostate cancer cell
      survival and proliferation and that exogenous FGFs may assume this function in
      the absence of endogenous FGF-2. Additionally, we provide the first evidence that
      FGFs regulate prostate GADD45alpha and GAS6 transcript content. The latter
      observations suggest that GADD45alpha and GAS6 proteins may be effectors of
      processes that regulate prostate cancer cell survival. Additional studies are
      required to examine this possibility in detail.

PMID- 15561783
TI  - Achievable steps toward building a National Health Information infrastructure in
      the United States.
AB  - Consensus is growing that a health care information and communication
      infrastructure is one key to fixing the crisis in the United States in health
      care quality, cost, and access. The National Health Information Infrastructure
      (NHII) is an initiative of the Department of Health and Human Services receiving
      bipartisan support. There are many possible courses toward its objective.
      Decision makers need to reflect carefully on which approaches are likely to work
      on a large enough scale to have the intended beneficial national impacts and
      which are better left to smaller projects within the boundaries of health care
      organizations. This report provides a primer for use by informatics professionals
      as they explain aspects of that dividing line to policy makers and to health care
      leaders and front-line providers. It then identifies short-term, intermediate,
      and long-term steps that might be taken by the NHII initiative.

PMID- 15561782
TI  - Promoting health literacy.
AB  - This report reviews some of the extensive literature in health literacy, much of
      it focused on the intersection of low literacy and the understanding of basic
      health care information. Several articles describe methods for assessing health
      literacy as well as methods for assessing the readability of texts, although
      generally these latter have not been developed with health materials in mind.
      Other studies have looked more closely at the mismatch between patients' literacy
      levels and the readability of materials intended for use by those patients. A
      number of studies have investigated the phenomenon of literacy from the
      perspective of patients' interactions in the health care setting, the
      disenfranchisement of some patients because of their low literacy skills, the
      difficulty some patients have in navigating the health care system, the quality
      of the communication between doctors and their patients including the cultural
      overlay of such exchanges, and ultimately the effect of low literacy on health
      outcomes. Finally, the impact of new information technologies has been studied by
      a number of investigators. There remain many opportunities for conducting further
      research to gain a better understanding of the complex interactions between
      general literacy, health literacy, information technologies, and the existing
      health care infrastructure.

PMID- 15561784
TI  - Accuracy of references in five biomedical informatics journals.
AB  - OBJECTIVE: To determine the rate and type of errors in biomedical informatics
      journal article references. METHODS: References in articles from the first 2004
      issues of five biomedical informatics journals, Journal of the American Medical
      Informatics Association, Journal of Biomedical Informatics, International Journal
      of Medical Informatics, Methods of Information in Medicine, and Artificial
      Intelligence in Medicine were compared with MEDLINE for journal, authors, title,
      year, volume, and page number accuracy. If discrepancies were identified, the
      reference was compared with the original publication. Two reviewers independently
      evaluated each reference. RESULTS: The five journal issues contained 37 articles.
      Among the 656 eligible references, 225 (34.3%) included at least one error. Among
      the 225 references, 311 errors were identified. One or more errors were found in
      the bibliography of 31 (84%) of the 37 articles. The reference error rates by
      journal ranged from 22.1% to 40.7%. Most errors (39.0%) occurred in the author
      element, followed by the journal (31.2%), title (17.7%), page (7.4%), year
      (3.5%), and volume (1.3%) information. CONCLUSION: The study identified a
      considerable error rate in the references of five biomedical informatics
      journals. Authors are responsible for the accuracy of references and should more
      carefully check them, possibly using informatics-based assistance.

PMID- 15561785
TI  - Communities' readiness for health information exchange: the National Landscape in
      2004.
AB  - BACKGROUND: The Secretary of Health and Human Services recently released a report
      calling for the nation to create a national health information network (NHIN)
      that would interconnect Regional Health Information Organizations (RHIOs). These
      RHIOs, which others have called Local or Regional Health Information
      Infrastructures (LHII), would in turn interconnect local as well as national
      health information resources. Little data exist about the activities taking place
      in communities to create LHIIs. APPROACH: The authors analyzed data that
      communities submitted in response to a request for capabilities issued by the
      Foundation for eHealth as part of their Connecting Communities for Better Health
      program using descriptive statistics and subjective evaluation. IMPRESSION: The
      authors analyzed data from 134 responses from communities in 42 states and the
      District of Columbia. Communities are enthusiastic about moving forward with
      health information exchange to create LHIIs to improve the efficiency, quality,
      and safety of care. They have identified significant local sources of investment
      and plan to use some clinical data standards but not as broadly as was expected.
      The communities have not yet developed the specific technical approaches or the
      sustainable business models that will be required. Many communities are
      interested in creating an LHII and are developing the leadership commitment
      needed to translate that interest into an operational reality. Clinical
      information standards can be incorporated into a community's plans as often as
      they need to be. Communities have to overcome funding issues, develop deeper
      understanding of the technical and organizational issues, and aggressively share
      their learning to succeed within their community and to help other communities
      succeed.

PMID- 15561786
TI  - Use of e-Health services between 1999 and 2002: a growing digital divide.
AB  - OBJECTIVE: To evaluate the patterns of e-Health use over a four-year period and
      the characteristics of users. DESIGN: Longitudinal, population-based study (1999
      2002) of members of a prepaid integrated delivery system. Available e-Health
      services included ordering prescription drug refills, scheduling appointments,
      and asking medical questions. MEASUREMENTS: Rates of known access to e-Health
      services, and of e-Health use each quarter. RESULTS: The number of members with
      known e-Health access increased from 51,336 (1.6%) in 1999 to 324,522 (9.3%), in
      2002. The percentage of households in which at least one person in the household
      had access increased from 2.7% to 14.1%. Among the subjects with known access,
      the percentage of subjects that used e-Health at least once increased from 25.7%
      in 1999 to 36.2% in 2002. In the multivariate analysis, subjects who had a low
      expected clinical need, were nonwhite, or lived in low socioeconomic status (SES)
      neighborhoods were less likely to have used e-Health services in 2002.
      Disparities by race/ethnicity and SES persisted after controlling for access to e
      Health and widened over time. CONCLUSION: Access to and use of e-Health services
      are growing rapidly. Use of these services appears to be greatest among persons
      with more medical need. The majority of subjects, however, do not use any e
      Health services. More research is needed to determine potential reasons for
      disparities in e-Health use by race/ethnicity and SES as well as the implications
      of these disparities on clinical outcomes.

PMID- 15561787
TI  - Server-based approach to web visualization of integrated three-dimensional brain
      imaging data.
AB  - The authors describe a client-server approach to three-dimensional (3-D)
      visualization of neuroimaging data, which enables researchers to visualize,
      manipulate, and analyze large brain imaging datasets over the Internet. All
      computationally intensive tasks are done by a graphics server that loads and
      processes image volumes and 3-D models, renders 3-D scenes, and sends the
      renderings back to the client. The authors discuss the system architecture and
      implementation and give several examples of client applications that allow
      visualization and analysis of integrated language map data from single and
      multiple patients.

PMID- 15561788
TI  - Validation of a discharge summary term search method to detect adverse events.
AB  - OBJECTIVE: Adverse events are poor health outcomes caused by medical care.
      Measuring them is necessary for quality improvements, but current detection
      methods are inadequate. We performed this study to validate a previously derived
      method of adverse event detection using term searching in physician-dictated
      discharge summaries. DESIGN: This was a retrospective, chart review study of a
      random sample of 245 adult medicine and surgery patients admitted to a
      multicampus academic medical center in 2002. MEASUREMENTS: The authors used a
      commercially available search engine to scan discharge summaries for the presence
      of 104 terms that potentially indicate an adverse event. Summaries with any of
      these terms were reviewed by a physician to determine the term's context. Screen
      positive summaries had a term that was contextually indicative of an adverse
      event. We used a two-stage chart review as the gold standard to determine the
      true presence or absence of an adverse event. RESULTS: The average patient age
      was 62 years (standard deviation 18.6) and 55% were admitted to a medical
      service. By gold standard criteria, 48 of 245 patients had an adverse event. Term
      searching classified 27 cases with an adverse event, with 11 true positives; 218
      cases were classified as not having an adverse event, with 181 true negatives.
      The sensitivity, specificity, and positive and negative predictive values were
      0.23 (95% confidence interval [CI]=0.11-0.35), 0.92 (95% CI=0.88-0.96), 0.41 (95%
      CI=0.25-0.59), and 0.83 (95% CI=95% 0.77-0.97), respectively. CONCLUSION:
      Although the sensitivity of the method is low, its high specificity means that
      the method could be used to replace expensive manual chart reviews by nurses.

PMID- 15561789
TI  - Text categorization models for high-quality article retrieval in internal
      medicine.
AB  - OBJECTIVE Finding the best scientific evidence that applies to a patient problem
      is becoming exceedingly difficult due to the exponential growth of medical
      publications. The objective of this study was to apply machine learning
      techniques to automatically identify high-quality, content-specific articles for
      one time period in internal medicine and compare their performance with previous
      Boolean-based PubMed clinical query filters of Haynes et al. DESIGN The selection
      criteria of the ACP Journal Club for articles in internal medicine were the basis
      for identifying high-quality articles in the areas of etiology, prognosis,
      diagnosis, and treatment. Naive Bayes, a specialized AdaBoost algorithm, and
      linear and polynomial support vector machines were applied to identify these
      articles. MEASUREMENTS The machine learning models were compared in each category
      with each other and with the clinical query filters using area under the receiver
      operating characteristic curves, 11-point average recall precision, and a
      sensitivity/specificity match method. RESULTS In most categories, the data
      induced models have better or comparable sensitivity, specificity, and precision
      than the clinical query filters. The polynomial support vector machine models
      perform the best among all learning methods in ranking the articles as evaluated
      by area under the receiver operating curve and 11-point average recall precision.
      CONCLUSION This research shows that, using machine learning methods, it is
      possible to automatically build models for retrieving high-quality, content
      specific articles using inclusion or citation by the ACP Journal Club as a gold
      standard in a given time period in internal medicine that perform better than the
      1994 PubMed clinical query filters.

PMID- 15561790
TI  - A statistical approach to scanning the biomedical literature for pharmacogenetics
      knowledge.
AB  - OBJECTIVE: Biomedical databases summarize current scientific knowledge, but they
      generally require years of laborious curation effort to build, focusing on
      identifying pertinent literature and data in the voluminous biomedical
      literature. It is difficult to manually extract useful information embedded in
      the large volumes of literature, and automated intelligent text analysis tools
      are becoming increasingly essential to assist in these curation activities. The
      goal of the authors was to develop an automated method to identify articles in
      Medline citations that contain pharmacogenetics data pertaining to gene-drug
      relationships. DESIGN: The authors built and evaluated several candidate
      statistical models that characterize pharmacogenetics articles in terms of word
      usage and the profile of Medical Subject Headings (MeSH) used in those articles.
      The best-performing model was used to scan the entire Medline article database
      (11 million articles) to identify candidate pharmacogenetics articles. RESULTS: A
      sampling of the articles identified from scanning Medline was reviewed by a
      pharmacologist to assess the precision of the method. The authors' approach
      identified 4,892 pharmacogenetics articles in the literature with 92% precision.
      Their automated method took a fraction of the time to acquire these articles
      compared with the time expected to be taken to accumulate them manually. The
      authors have built a Web resource
      (http://pharmdemo.stanford.edu/pharmdb/main.spy) to provide access to their
      results. CONCLUSION: A statistical classification approach can screen the primary
      literature to pharmacogenetics articles with high precision. Such methods may
      assist curators in acquiring pertinent literature in building biomedical
      databases.

PMID- 15561791
TI  - Using Petri Net tools to study properties and dynamics of biological systems.
AB  - Petri Nets (PNs) and their extensions are promising methods for modeling and
      simulating biological systems. We surveyed PN formalisms and tools and compared
      them based on their mathematical capabilities as well as by their appropriateness
      to represent typical biological processes. We measured the ability of these tools
      to model specific features of biological systems and answer a set of biological
      questions that we defined. We found that different tools are required to provide
      all capabilities that we assessed. We created software to translate a generic PN
      model into most of the formalisms and tools discussed. We have also made
      available three models and suggest that a library of such models would catalyze
      progress in qualitative modeling via PNs. Development and wide adoption of common
      formats would enable researchers to share models and use different tools to
      analyze them without the need to convert to proprietary formats.

PMID- 15561792
TI  - Answering physicians' clinical questions: obstacles and potential solutions.
AB  - OBJECTIVE: To identify the most frequent obstacles preventing physicians from
      answering their patient-care questions and the most requested improvements to
      clinical information resources. DESIGN: Qualitative analysis of questions asked
      by 48 randomly selected generalist physicians during ambulatory care.
      MEASUREMENTS: Frequency of reported obstacles to answering patient-care questions
      and recommendations from physicians for improving clinical information resources.
      RESULTS: The physicians asked 1,062 questions but pursued answers to only 585
      (55%). The most commonly reported obstacle to the pursuit of an answer was the
      physician's doubt that an answer existed (52 questions, 11%). Among pursued
      questions, the most common obstacle was the failure of the selected resource to
      provide an answer (153 questions, 26%). During audiotaped interviews, physicians
      made 80 recommendations for improving clinical information resources. For
      example, they requested comprehensive resources that answer questions likely to
      occur in practice with emphasis on treatment and bottom-line advice. They asked
      for help in locating information quickly by using lists, tables, bolded
      subheadings, and algorithms and by avoiding lengthy, uninterrupted prose.
      CONCLUSION: Physicians do not seek answers to many of their questions, often
      suspecting a lack of usable information. When they do seek answers, they often
      cannot find the information they need. Clinical resource developers could use the
      recommendations made by practicing physicians to provide resources that are more
      useful for answering clinical questions.

PMID- 15561793
TI  - Frequency of laboratory test utilization in the intensive care unit and its
      implications for large-scale data collection efforts.
AB  - OBJECTIVE: Mapping local use names to standardized nomenclatures such as LOINC
      (Logical Observation Identifiers Names and Codes) is a time-consuming task when
      done retrospectively or during the configuration of new information systems. The
      author sought to identify a subset of intensive care unit (ICU) laboratory tests,
      which, because of their frequency of use, should be the focus of efforts to
      standardize test names in ICU information systems. DESIGN: The author reviewed
      the ordering practices in medical, surgical, and pediatric ICUs within a large
      university teaching hospital to identify the subset of laboratory tests that
      represented the majority of tests performed in these settings. The author
      compared the results of his findings with the laboratory tests required to
      complete several of the most frequently used ICU acuity scoring systems. RESULTS:
      It was found that between 104 and 202 tests and profiles represented 99% of all
      testing in the three ICUs. All the laboratory studies needed for six commonly
      used ICU scoring systems fell into the top 21 laboratory studies and profiles
      performed in each ICU. CONCLUSION: The author identified a small subset of the
      LOINC database that should be the focus of efforts to standardize test names in
      ICU information systems. Mapping this subset of laboratory tests and profiles to
      LOINC vocabulary will simplify the process of collecting data for large-scale
      databases such as ICU scoring systems and the configuration of new ICU
      information systems.

PMID- 15561794
TI  - Creating the web-based intensive care unit safety reporting system.
AB  - In an effort to improve patient safety, researchers at the Johns Hopkins
      University designed and implemented a comprehensive Web-based Intensive Care Unit
      Safety Reporting System (ICUSRS). The ICUSRS collects data about adverse events
      and near misses from all staff in the ICU. This report reflects data on 854
      reports from 18 diverse ICUs across the United States. Reporting is voluntary,
      and data collected is confidential, with patient, provider, and reporter
      information deidentified. Preliminary data include system factors reported,
      degree of patient harm, reporting times, and evaluations of the system.
      Qualitative and quantitative data are reported back to the ICU site study teams
      and frontline staff through monthly reports, case discussions, and a quarterly
      newsletter.

PMID- 15561795
TI  - Use of a computerized guideline for glucose regulation in the intensive care unit
      improved both guideline adherence and glucose regulation.
AB  - OBJECTIVE: To measure the impact of a computerized guideline for glucose
      regulation in an ICU. DESIGN: A randomized, controlled trial with an off-on-off
      design. METHODS: We implemented a glucose regulation guideline in an intensive
      care unit in paper form during the first study period. During the second period,
      the guideline was randomly applied in either paper or computerized form. In the
      third period, the guideline was available only in paper form. MEASUREMENTS AND
      RESULTS: We analyzed data for 484 patients. During the intervention period, the
      control group included 54 patients and the computerized intervention group
      included 66 patients. The two guideline-related outcome measures consisted of
      compliance with: (a) glucose measurement timing recommendations and (b) insulin
      dose advice. We measured clinical impact as the proportion of time that glucose
      levels fell within target range. In the first (paper-based) study period, 29.0%
      of samples occurred with optimal timing; during the second period, this increased
      to 35.5% for paper-based and to 40.2% for computerized protocols. The third study
      period timeliness scores reverted to the first period rates. Late (suboptimal)
      sampling occurred for 66% of glucose measurements in the first study period, for
      42% of paper-based and 28% of computer-based protocol samples in the second
      period, and for 50.0% of samples in the third study period. In the first study
      period, insulin-dosing guideline compliance was 56.3%; in the second period, it
      was 64.2% for paper-based and 77.3% for computer-based protocols, and it fell to
      42.4% in the third period. For the second study period, the time that a patient's
      glucose values fell within target range improved for both the control (52.9%) and
      the computerized groups (54.2%) compared with the first study period (44.3%) and
      the third period (42.3%). CONCLUSION: Implementing a computerized version of a
      guideline significantly improved timeliness of measurements and glucose level
      regulation for critically ill patients compared with implementing a paper-based
      version of the guideline.

PMID- 15561796
TI  - A Tyr-W-MIF-1 analog containing D-Pro2 acts as a selective mu2-opioid receptor
      antagonist in the mouse.
AB  - The antagonistic properties of Tyr-d-Pro-Trp-Gly-NH(2) (d-Pro(2)-Tyr-W-MIF-1), a
      Tyr-Pro-Trp-Gly-NH(2)(Tyr-W-MIF-1) analog, on the antinociception induced by the
      mu-opioid receptor agonists Tyr-W-MIF-1, [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]
      enkephalin (DAMGO), Tyr-Pro-Trp-Phe-NH(2) (endomorphin-1), and Tyr-Pro-Phe-Phe
      NH(2) (endomorphin-2) were studied in the mouse paw-withdrawal test. d-Pro(2)-Tyr
      W-MIF-1 injected intrathecally (i.t.) had no apparent effect on the thermal
      nociceptive threshold. d-Pro(2)-Tyr-W-MIF-1 (0.1-0.4 nmol) coadministered i.t.
      showed a dose-dependent attenuation of the antinociception induced by Tyr-W-MIF-1
      without affecting endomorphin- or DAMGO-induced antinociception. However, higher
      doses of d-Pro(2)-Tyr-W-MIF-1 (0.8-1.2 nmol) significantly attenuated endomorphin
      1- or DAMGO-induced antinociception, whereas the antinociception induced by
      endomorphin-2 was still not affected by d-Pro(2)-Tyr-W-MIF-1. Pretreatment i.t.
      with various doses of naloxonazine, a mu(1)-opioid receptor antagonist,
      attenuated the antinociception induced by Tyr-W-MIF-1, endomorphin-1, endomorphin
      2, or DAMGO. Judging from the ID(50) values for naloxonazine against the
      antinociception induced by the mu-opioid receptor agonists, the antinociceptive
      effect of Tyr-W-MIF-1 is extremely less sensitive to naloxonazine than those of
      endomorphin-1 or DAMGO. In contrast, endomorphin-2-induced antinociception is
      extremely sensitive to naloxonazine. The present results clearly suggest that d
      Pro(2)-Tyr-W-MIF-1 is the selective antagonist to be identified for the mu(2)
      opioid receptor in the mouse spinal cord. d-Pro(2)-Tyr-W-MIF-1 may also
      discriminate between Tyr-W-MIF-1-induced antinociception and the antinociception
      induced by endomorphin-1 or DAMGO, all of which show a preference for the mu(2)
      opioid receptor in the spinal cord.

PMID- 15561797
TI  - Differences in tail vascular bed reactivity in rats with and without heart
      failure following myocardial infarction.
AB  - Myocardial infarction (MI) was induced in rats by coronary ligation to compare
      changes in vascular reactivity from animals that developed heart failure (InfHF)
      with those that did not (Inf). Infarct size was similar in both groups. In vitro
      preparations of tail vascular bed were used to investigate the vascular responses
      to acetylcholine, sodium nitroprusside, and phenylephrine. Acetylcholine-induced
      relaxation was impaired in the Inf group (53 +/- 2%, n = 6) when compared with
      Sham (80 +/- 2%, n = 6, P < 0.05). The maximal response (E(max)) to phenylephrine
      increased in the Inf group (423 +/- 10 mm Hg, n = 9, P < 0.01) and decreased in
      InfHF (279 +/- 10 mm Hg, n = 7, P < 0.05) when compared with Sham (319 +/- 11 mm
      Hg, n = 8). Regardless of endothelial integrity, E(max) to phenylephrine
      increased in the Inf, nitro-l-arginine methyl ester, and indomethacin groups. An
      increased release of a prostanoid vasodilator was detected in the Inf group.
      Differently, the InfHF group presented a reduction of the E(max) to phenylephrine
      and an increment of nitric oxide release. This study demonstrates that MI without
      heart failure impairs endothelium-dependent relaxation and increases the
      reactivity to phenylephrine. This increase seems to involve a muscular component.
      The endothelium participates with an increased release of a vasodilator
      prostanoid, possibly to compensate the increased smooth muscle response. When
      heart failure follows MI, the reactivity to phenylephrine decreases, possibly due
      to an increased nitric oxide release.

PMID- 15561798
TI  - Induction of nitric oxide production by the cytostatic macrolide apicularen A
      [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14
      dihydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)
      (9CI)] and possible role of nitric oxide in apicularen A-induced apoptosis in RAW
      264.7 cells.
AB  - We previously reported that apicularen A [2,4-heptadienamide, N-[(1E)-3
      [(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14 dihydroxy-1-oxo-5,9-epoxy-1H-2
      benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)], a highly cytostatic
      macrolide isolated from the myxobacterial genus Chondromyces, induces apoptosis
      in the mouse leukemic monocyte cell line RAW 264.7. To analyze the action
      mechanism of apicularen A for the induction of apoptosis, effects of apicularen A
      on nitric oxide (NO) production in RAW 264.7 cells were examined. It was
      demonstrated that apicularen A at 10 and 100 nM induced nitrite production,
      whereas apicularen B [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-7-[[2
      (acetylamino)-2-deoxy-beta-d-glucopyranosyl]oxy]-3,4,5,6,7,8,9,10-octahydro-14
      hydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)
      (9CI)], an N-acetyl-glucosamine glycoside of apicularen A, had no effect at 100
      nM. The apicularen A-induced nitrite production was accompanied by an increase in
      the level of inducible nitric-oxide synthase (iNOS) and its mRNA and was
      suppressed by the NOS inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA). In
      addition, apicularen A activated nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1) and decreased the level of IkappaB-alpha and increased that of
      phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, the apicularen A
      induced nitrite production was suppressed by the NF-kappaB inhibitor Bay 11-7082
      [(E)-3-(4-methylphenylsulfonyl)-2-propenenitrile] and the JNK inhibitor SP600125
      [anthra[1,9-cd]pyrazol-6(2H)-one]. These findings suggested that apicularen A
      activates NF-kappaB and AP-1, thus triggering the expression of iNOS mRNA and
      iNOS protein and induces NO production. Finally, apicularen A decreased cell
      growth and survival and cell viability and disrupted the mitochondrial membrane
      potential. The addition of l-NMMA partially recovered the apicularen A-induced
      decrease in cell growth and survival and cell viability and the disruption of
      mitochondrial membrane potential. These findings suggested that NO produced by
      apicularen A treatment participate partially in the apicularen A-induced
      apoptosis in RAW 264.7 cells.

PMID- 15561799
TI  - The molecular-genetic basis of functional hyperandrogenism and the polycystic
      ovary syndrome.
AB  - The genetic mechanisms underlying functional hyperandrogenism and the polycystic
      ovary syndrome (PCOS) remain largely unknown. Given the large number of genetic
      variants found in association with these disorders, the emerging picture is that
      of a complex multigenic trait in which environmental influences play an important
      role in the expression of the hyperandrogenic phenotype. Among others, genomic
      variants in genes related to the regulation of androgen biosynthesis and
      function, insulin resistance, and the metabolic syndrome, and proinflammatory
      genotypes may be involved in the genetic predisposition to functional
      hyperandrogenism and PCOS. The elucidation of the molecular genetic basis of
      these disorders has been burdened by the heterogeneity in the diagnostic criteria
      used to define PCOS, the limited sample size of the studies conducted to date,
      and the lack of precision in the identification of ethnic and environmental
      factors that trigger the development of hyperandrogenic disorders. Progress in
      this area requires adequately sized multicenter collaborative studies after
      standardization of the diagnostic criteria used to classify hyperandrogenic
      patients, in whom modifying environmental factors such as ethnicity, diet, and
      lifestyle are identified with precision. In addition to classic molecular genetic
      techniques such as linkage analysis in the form of a whole-genome scan and large
      case-control studies, promising genomic and proteomic approaches will be
      paramount to our understanding of the pathogenesis of functional hyperandrogenism
      and PCOS, allowing a more precise prevention, diagnosis, and treatment of these
      prevalent disorders.

PMID- 15561800
TI  - Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their
      receptors in humans.
AB  - In human beings, two forms of GnRH, termed GnRH-I and GnRH-II, encoded by
      separate genes have been identified. Although these hormones share comparable
      cDNA and genomic structures, their tissue distribution and regulation of gene
      expression are significantly dissimilar. The actions of GnRH are mediated by the
      GnRH receptor, which belongs to a member of the rhodopsin-like G protein-coupled
      receptor superfamily. However, to date, only one conventional GnRH receptor
      subtype (type I GnRH receptor) uniquely lacking a carboxyl-terminal tail has been
      found in the human body. Studies on the transcriptional regulation of the human
      GnRH receptor gene have indicated that tissue-specific gene expression is
      mediated by differential promoter usage in various cell types. Functionally,
      there is growing evidence showing that both GnRH-I and GnRH-II are potentially
      important autocrine and/or paracrine regulators in some extrapituitary
      compartments. Recent cloning of a second GnRH receptor subtype (type II GnRH
      receptor) in nonhuman primates revealed that it is structurally and functionally
      distinct from the mammalian type I receptor. However, the human type II receptor
      gene homolog carries a frameshift and a premature stop codon, suggesting that a
      full-length type II receptor does not exist in humans.

PMID- 15561801
TI  - Nuclear hormone receptor coregulator: role in hormone action, metabolism, growth,
      and development.
AB  - Nuclear hormone receptor coregulator (NRC) (also referred to as activating signal
      cointegrator-2, thyroid hormone receptor-binding protein, peroxisome proliferator
      activating receptor-interacting protein, and 250-kDa receptor associated protein)
      belongs to a growing class of nuclear cofactors widely known as coregulators or
      coactivators that are necessary for transcriptional activation of target genes.
      The NRC gene is also amplified and overexpressed in breast, colon, and lung
      cancers. NRC is a 2063-amino acid protein that harbors a potent N-terminal
      activation domain (AD1) and a second more centrally located activation domain
      (AD2) that is rich in Glu and Pro. Near AD2 is a receptor-interacting domain
      containing an LxxLL motif (LxxLL-1), which interacts with a wide variety of
      ligand-bound nuclear hormone receptors with high affinity. A second LxxLL motif
      (LxxLL-2) located in the C-terminal region of NRC is more restricted in its
      nuclear hormone receptor specificity. The intrinsic activation potential of NRC
      is regulated by a C-terminal serine, threonine, leucine-regulatory domain. The
      potential role of NRC as a cointegrator is suggested by its ability to enhance
      transcriptional activation of a wide variety of transcription factors and from
      its in vivo association with a number of known transcriptional regulators
      including CBP/p300. Recent studies in mice indicate that deletion of both NRC
      alleles leads to embryonic lethality resulting from general growth retardation
      coupled with developmental defects in the heart, liver, brain, and placenta. NRC(
      /-) mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the
      importance of NRC as a prosurvival and antiapoptotic gene. Studies with 129S6
      NRC(+/-) mice indicate that NRC is a pleiotropic regulator that is involved in
      growth, development, reproduction, metabolism, and wound healing.

PMID- 15561802
TI  - Steroid sulfatase: molecular biology, regulation, and inhibition.
AB  - Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl
      steroid sulfates and therefore has a pivotal role in regulating the formation of
      biologically active steroids. The enzyme is widely distributed throughout the
      body, and its action is implicated in physiological processes and pathological
      conditions. The crystal structure of the enzyme has been resolved, but relatively
      little is known about what regulates its expression or activity. Research into
      the control and inhibition of this enzyme has been stimulated by its important
      role in supporting the growth of hormone-dependent tumors of the breast and
      prostate. STS is responsible for the hydrolysis of estrone sulfate and
      dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone,
      respectively, both of which can be converted to steroids with estrogenic
      properties (i.e., estradiol and androstenediol) that can stimulate tumor growth.
      STS expression is increased in breast tumors and has prognostic significance. The
      role of STS in supporting tumor growth prompted the development of potent STS
      inhibitors. Several steroidal and nonsteroidal STS inhibitors are now available,
      with the irreversible type of inhibitor having a phenol sulfamate ester as its
      active pharmacophore. One such inhibitor, 667 COUMATE, has now entered a phase I
      trial in postmenopausal women with breast cancer. The skin is also an important
      site of STS activity, and deficiency of this enzyme is associated with X-linked
      ichthyosis. STS may also be involved in regulating part of the immune response
      and some aspects of cognitive function. The development of potent STS inhibitors
      will allow investigation of the role of this enzyme in physiological and
      pathological processes.

PMID- 15561803
TI  - Molecular endocrinology and physiology of the aging central nervous system.
AB  - Aging is associated with a progressive decline in physical and cognitive
      functions. The impact of age-dependent endocrine changes regulated by the central
      nervous system on the dynamics of neuronal behavior, neurodegeneration,
      cognition, biological rhythms, sexual behavior, and metabolism are reviewed. We
      also briefly review how functional deficits associated with increases in
      glucocorticoids and cytokines and declining production of sex steroids, GH, and
      IGF are likely exacerbated by age-dependent molecular misreading and alterations
      in components of signal transduction pathways and transcription factors.

PMID- 15561804
TI  - Ductal lavage and risk assessment of breast cancer.
AB  - Following recent advances in breast cancer chemoprevention, much emphasis has
      been placed on risk assessment to evaluate whether women at increased risk for
      developing breast cancer should proceed with breast cancer risk reduction
      strategies. The currently available risk-reduction approaches include screening,
      chemoprevention, and preventive surgeries. Breast cancer arises from the
      epithelial linings of the ductal system, and it is believed that hyperplasia and
      atypical hyperplasia represent early changes in the breast carcinogenesis
      process. The ductal lavage procedure offers a minimally invasive method to obtain
      breast epithelial cells from the ductal system for cytopathologic analysis to
      provide individualized risk assessment. This paper reviews breast cancer risk
      factors, with an emphasis on cytological atypia and the role of ductal lavage in
      breast cancer risk assessment.

PMID- 15561805
TI  - Prognostic and predictive factors in early-stage breast cancer.
AB  - Breast cancer is the most common malignancy among American women. Due to
      increased screening, the majority of patients present with early-stage breast
      cancer. The Oxford Overview Analysis demonstrates that adjuvant hormonal therapy
      and polychemotherapy reduce the risk of recurrence and death from breast cancer.
      Adjuvant systemic therapy, however, has associated risks and it would be useful
      to be able to optimally select patients most likely to benefit. The purpose of
      adjuvant systemic therapy is to eradicate distant micrometastatic deposits. It is
      essential therefore to be able to estimate an individual patient's risk of
      harboring clinically silent micrometastatic disease using established prognostic
      factors. It is also beneficial to be able to select the optimal adjuvant therapy
      for an individual patient based on established predictive factors. It is standard
      practice to administer systemic therapy to all patients with lymph node-positive
      disease. However, there are clearly differences among node-positive women that
      may warrant a more aggressive therapeutic approach. Furthermore, there are many
      node-negative women who would also benefit from adjuvant systemic therapy.
      Prognostic factors therefore must be differentiated from predictive factors. A
      prognostic factor is any measurement available at the time of surgery that
      correlates with disease-free or overall survival in the absence of systemic
      adjuvant therapy and, as a result, is able to correlate with the natural history
      of the disease. In contrast, a predictive factor is any measurement associated
      with response to a given therapy. Some factors, such as hormone receptors and
      HER2/neu overexpression, are both prognostic and predictive.

PMID- 15561806
TI  - Facts and controversies in systemic treatment of metastatic breast cancer.
AB  - The management of metastatic breast cancer remains an important and controversial
      issue. The systemic therapy, comprising endocrine, cytotoxic and biological
      agents, can be administered sequentially or in combination. Few drugs or
      combinations provide a significant improvement in survival and, therefore, in the
      great majority of cases, treatment is given with a palliative intent. With the
      exception of first-line therapy, for which general agreement exists, currently
      there is no consensual standard of care. This review will summarize the current
      knowledge and outline the controversial issues related to systemic therapy of
      metastatic breast cancer, with emphasis on treatment tailoring. The potential
      role of tumor molecular profile(s) in the selection of patients that could
      benefit the most from each strategy/agent will be discussed.

PMID- 15561807
TI  - The role of PET scan in diagnosis, staging, and management of non-small cell lung
      cancer.
AB  - Positron emission tomography (PET) is now an important cancer imaging tool, both
      for diagnosis and staging, as well as offering prognostic information based on
      response. This report attempts to comprehensively review the value of PET in the
      locoregional and distant staging of non-small cell lung cancer (NSCLC),
      illustrate the potential effects on patient management, and give a short overview
      of newer applications. PET sets the gold standard in the evaluation of an
      indeterminate solitary pulmonary nodule or mass, where PET has proven to be
      significantly more accurate than computed tomography (CT) in the distinction
      between benign and malignant lesions. In the evaluation of metastatic spread to
      locoregional lymph nodes, PET is significantly more accurate than CT, so that
      invasive surgical staging may be omitted in many patients with negative
      mediastinal PET images. In patients with positive mediastinal PET images,
      invasive surgical staging remains mandatory because of the possibility of false
      positive findings due to inflammatory nodes or granulomatous disorders. In the
      search for metastatic spread, PET is a useful adjunct to conventional imaging.
      This may be due to the finding of unexpected metastatic lesions or due to
      exclusion of malignancy in lesions that are equivocal on standard imaging.
      However, at this time, PET does not replace conventional imaging. Large-scale
      randomized studies are currently examining whether PET staging will actually
      improve the appearance of lung cancer outcome.

PMID- 15561808
TI  - Carcinoma of unknown primary site: sequential treatment with
      paclitaxel/carboplatin/etoposide and gemcitabine/irinotecan: a Minnie Pearl
      Cancer Research Network phase II trial.
AB  - PURPOSE: To evaluate the efficacy and toxicity of the sequential administration
      of paclitaxel (Taxol; Bristol-Myers Squibb; Princeton, NJ), carboplatin
      (Paraplatin; Bristol-Myers Squibb), and oral etoposide (VePesid; Bristol-Myers
      Squibb) followed by gemcitabine (Gemzar; Eli Lilly; Indianapolis, IN) and
      irinotecan (Campostar; Pfizer Pharmaceuticals; New York, NY) in the first-line
      treatment of patients with carcinoma of unknown primary site. PATIENTS AND
      METHODS: One hundred thirty-two patients were treated with sequential combination
      chemotherapy for a maximum of six cycles. All patients had relatively poor
      prognostic features. Fifty-nine patients had well-differentiated adenocarcinoma,
      73 patients had poorly differentiated carcinoma, and 121 patients had performance
      status scores of 0 or 1. RESULTS: Thirty-three (30%) of 111 assessable patients
      (95% confidence interval 27%-33%) had objective responses to treatment (26
      partial responses, seven complete responses). The combination of gemcitabine and
      irinotecan was associated with significantly less toxicity than the triple-drug
      regimen and improved the responses in several patients (10%). The response rates
      were similar in the two major histologic tumor types, but were lower for patients
      with liver-dominant tumors (13%) and higher for patients with lymph-node-dominant
      tumors (50%). The median progression-free survival time, median survival time,
      and actuarial survival rates at 1 and 2 years were 5.7 months, 9.1 months, 35%,
      and 16%, respectively. CONCLUSIONS: Sequential combination chemotherapy with
      paclitaxel/carboplatin/oral etoposide and gemcitabine/irinotecan is an active
      treatment for patients with carcinoma of unknown primary site, but overall
      toxicities are greater than those seen with other combinations of new drugs and
      survival appears similar to that observed in 264 other patients treated in our
      four previous phase II trials. A better understanding of the biology of these
      heterogeneous tumors will likely lead to improved therapy for these patients.

PMID- 15561809
TI  - The past decade of experience with isolated hepatic perfusion.
AB  - Metastatic or primary unresectable cancers confined to the liver are the sole or
      life-limiting component of disease for many patients with colorectal cancer,
      ocular melanoma, neuroendocrine tumors, or primary colangio- or hepatocellular
      carcinomas. Regional treatment strategies including infusional chemotherapy and
      local ablative therapy are under investigation, but have limitations with respect
      to the clinical conditions under which they can be employed. Isolated hepatic
      perfusion (IHP) was first clinically applied over 40 years ago, but because of
      its technical complexity, the attendant potential morbidity, and the lack of
      documented efficacy, it has not enjoyed consistent or widespread evaluation. In
      light of the antitumor activity with isolated limb perfusion with tumor necrosis
      factor (TNF) and melphalan in patients with unresectable extremity sarcoma or in
      transit melanoma, this regimen has been administered via IHP at several centers
      worldwide for patients with unresectable liver cancers. IHP with TNF and
      melphalan can result in significant regression of advanced refractory cancers
      from multiple histologies confined to the liver. Patient selection is important
      to ensure good results with minimal morbidity and mortality. Work to define the
      appropriate clinical groups is ongoing at many clinical centers.

PMID- 15561810
TI  - A meta-analysis of the timing of chest irradiation in the combined modality
      treatment of limited-stage small cell lung cancer.
AB  - The objective of this study was to determine whether initial combined
      chemoradiation results in superior 1-, 2-, and 3-year survivals in the treatment
      of limited-stage small cell lung cancer versus sequential or split-course
      therapy. Using a prospective meta-analysis protocol outlining study inclusion
      criteria, literature search strategy, and statistical procedures, data from all
      available randomized controlled trials addressing the above-noted objective were
      pooled using a fixed effects model (Peto). Results were expressed as summary odds
      ratios (ORp), and statistical tests for data heterogeneity were performed prior
      to calculation of ORps. Odds ratios greater than 1.0 favored the experimental arm
      versus control (i.e., early chest irradiation). If statistical heterogeneity was
      demonstrated, sensitivity analyses were performed by previously described methods
      to evaluate possible sources of heterogeneity across the included studies.
      Pooling data from eight randomized controlled trials enrolling over 1,500
      patients showed that early integration of chest radiotherapy with systemic
      chemotherapy increases overall survival by 34%-216%, depending on the end point
      of interest. Etoposide (E) plus cisplatin (P) in conjunction with chest
      irradiation appears to offer the greatest increase in survival versus delayed or
      split-course radiation therapy and non-EP-containing drug schedules. The
      available randomized trial data support early concurrent chest radiotherapy and
      systemic chemotherapy in the form of E and P in the management of limited-stage
      small cell lung cancer.

PMID- 15561811
TI  - Granisetron: an update on its clinical use in the management of nausea and
      vomiting.
AB  - Nausea and vomiting are typical side effects of cytotoxic therapy and some
      surgical procedures. These symptoms can represent a major therapeutic challenge
      and, if inadequately controlled by antiemetic treatment, will result in increased
      mortality, morbidity, and health care costs. However, the management of nausea
      and vomiting has improved greatly in recent years following the introduction of
      the 5-HT3-receptor antagonists, known as 'setrons.' In light of recent
      developments in antiemetic care, including the approval of the first neurokinin-1
      receptor antagonist aprepitant (Emend; Merck and Company, Inc.; West Point, PA)
      and a new 5-HT3 receptor antagonist palonosetron (Aloxi; MGI Pharma; Minneapolis,
      MN), this article provides an update on the clinical experience gained with the 5
      HT3-receptor antagonist granisetron (Kytril; Roche Laboratories, Inc.; Nutley,
      NJ) for the management of chemotherapy-induced, radiation-induced, and
      postoperative nausea and vomiting, and also reviews its use in special patient
      populations. Granisetron is a potent and highly selective 5-HT3-receptor
      antagonist that has little or no affinity for other receptors, a characteristic
      that is thought to underlie the favorable side-effect and safety profiles of this
      agent. Extensive clinical trial data have shown granisetron to be an effective
      and well-tolerated agent for the treatment of nausea and vomiting in the oncology
      and surgical settings. Granisetron has also been shown to be effective and well
      tolerated in special populations, such as patients refractory to antiemetic
      treatment, patients with hepatic or renal impairment, and children. Data also
      suggest that its safety profile and minimal potential for drug-drug interactions
      would make it an antiemetic agent of choice for elderly cancer patients.

PMID- 15561812
TI  - Safety and pain palliation of zoledronic acid in patients with breast cancer,
      prostate cancer, or multiple myeloma who previously received bisphosphonate
      therapy.
AB  - An open-label study conducted in community centers assessed the safety of
      zoledronic acid 4 mg intravenously over 15 minutes every 3-4 weeks as treatment
      of bone metastases in patients with multiple myeloma, breast cancer, or prostate
      cancer with and without previous bisphosphonate exposure. Adverse events (AEs),
      pain, and quality-of-life (QOL) scores were recorded, and serum creatinine (SCr)
      levels were measured before each infusion. Of 638 patients, 415 patients (65%)
      had received prior bisphosphonate therapy. Fatigue, nausea, and arthralgia were
      the most frequent AEs. Nausea was more common in bisphosphonate-naive patients.
      SCr levels increased notably in 6.6% of patients: 7.7% of patients who received
      prior bisphosphonate therapy and 4.5% of bisphosphonate-naive patients. Treatment
      was delayed because of SCr-level increases in 1.4% of patients with prior
      bisphosphonate exposure and 0.4% of bisphosphonate-naive patients. SCr-level
      increases and treatment delays did not correlate with duration of prior
      bisphosphonate therapy. There was a trend towards more treatment discontinuations
      in patients with prior bisphosphonate exposure compared with bisphosphonate-naive
      patients. Pain scores decreased from baseline; total QOL scores remained
      constant. The results of this study suggest that, with proper SCr-level
      monitoring, cancer patients with bone metastases who have previously received
      intravenous bisphosphonate treatment can be safely converted to zoledronic acid
      therapy.

PMID- 15561813
TI  - A randomized comparison of every-2-week darbepoetin alfa and weekly epoetin alfa
      for the treatment of chemotherapy-induced anemia in patients with breast, lung,
      or gynecologic cancer.
AB  - An important clinical question is the relative efficacy of the most common
      dosages of darbepoetin alfa (Aranesp; Amgen Inc.; Thousand Oaks, CA) 200 microg
      every 2 weeks (Q2W) and epoetin alfa (Procrit; Ortho Biotech Products, LP;
      Raritan, NJ) 40,000 U weekly (QW) for the treatment of chemotherapy-induced
      anemia. We designed three concurrent randomized, open-label, multicenter,
      identical trials (with the exception of tumor type criteria of breast,
      gynecologic, or lung cancer) of darbepoetin alfa and epoetin alfa in patients
      with chemotherapy-induced anemia to validate the Patient Satisfaction
      Questionnaire for Anemia (PSQ-An) treatment tool and to compare the efficacies
      and safety profiles of these two agents. In each trial, patients were randomized
      1:1 to receive either darbepoetin alfa at a dose of 200 microg Q2W or epoetin
      alfa at a dose of 40,000 U QW for up to 16 weeks. The PSQ-An was assessed for
      validity, feasibility, and reliability. Secondary clinical endpoints were
      analyzed using the primary analysis set. Both individual trial analyses and a
      protocol-specified combined analysis of data from all three trials were
      conducted. Overall, 312 patients (157 darbepoetin alfa; 155 epoetin alfa) were
      randomized and received study drug. Baseline characteristics were similar in both
      treatment groups in each trial and overall. The PSQ-An was valid, feasible, and
      reliable. In general, no difference between treatment groups was observed for
      hemoglobin- and transfusion-based endpoints in each individual trial or in the
      combined analysis. From exploratory analyses, achievement and maintenance of a
      hemoglobin target range (11-13 g/dl) were similar in both groups. No differences
      in safety were observed. With the PSQ-An, formal comparisons of the impact of
      anemia therapies on patients and caregivers can be made in future prospective
      studies. Further, darbepoetin alfa (200 microg Q2W) and epoetin alfa (40,000 U
      QW) appear to achieve comparable clinical and hematologic outcomes.

PMID- 15561814
TI  - Cancer as metaphor.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at
      MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and
      advancing compassionate health care delivery, which provides hope to the patient
      and support to caregivers and encourages the healing process. The center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers, and gain insight and support from fellow staff members.
      Metaphors illuminate complex issues and can paint a thousand words. However,
      fundamental to individual and collective expression, they are also capable of
      creating or perpetuating stereotypes, and stigma. In oncology, the military
      metaphor is perhaps the most prominent, with the high profile of the "War on
      Cancer," and the imperative for patients to have a fighting spirit. Balancing the
      instinct to fight with words of healing and acceptance remains a challenge. The
      history of the military metaphor and how the humanities have illuminated cancer
      as a metaphor are reviewed. The advantages and disadvantages of the use of this
      metaphor are discussed, as well as the use of other metaphors in the psychosocial
      dynamic of care.

PMID- 15561815
TI  - The molecular perspective: morphine.

PMID- 15561816
TI  - "The patient failed chemotherapy" ...an expunged phrase.

PMID- 15561817
TI  - A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results
      in sensitivity to drugs targeting eukaryotic topoisomerase II.
AB  - Fluoroquinolones are broad-spectrum antimicrobial agents that target type II
      topoisomerases. Many fluoroquinolones are highly specific for bacterial type II
      topoisomerases and act against both DNA gyrase and topoisomerase IV. In
      Escherichia coli, mutations causing quinolone resistance are often found in the
      gene that encodes the A subunit of DNA gyrase. One common site for resistance
      conferring mutations alters Ser83, and mutations to Leu or Trp result in high
      levels of resistance to fluoroquinolones. In the present study we demonstrate
      that the mutation of Ser83 to Trp in DNA gyrase (Gyr(S83W)) also results in
      sensitivity to agents that are potent inhibitors of eukaryotic topoisomerase II
      but that are normally inactive against prokaryotic enzymes. Epipodophyllotoxins,
      such as etoposide, teniposide and amino-azatoxin, inhibited the DNA supercoiling
      activity of Gyr(S83W), and the enzyme caused elevated levels of DNA cleavage in
      the presence of these agents. The DNA sequence preference for Gyr(S83W)-induced
      cleavage sites in the presence of etoposide was similar to that seen with
      eukaryotic type II topoisomerases. Introduction of the Gyr(S83W) mutation in E.
      coli strain RFM443-242 by site-directed mutagenesis sensitized it to
      epipodophyllotoxins and amino-azatoxin. Our results demonstrate that sensitivity
      to agents that target topoisomerase II is conserved between prokaryotic and
      eukaryotic enzymes, suggesting that drug interaction domains are also well
      conserved and likely occur in domains important for the biochemical activities of
      the enzymes.

PMID- 15561818
TI  - CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1.
AB  - Overexpression of CDR1, an efflux pump, is one of the major mechanisms
      contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed
      and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene
      could be used as the reporter to monitor the activity of the CDR1 promoter.
      Overexpression of CaNDT80, the C. albicans homolog of S. cerevisiae NDT80,
      increases the beta-galactosidase activity of the CDR1 p-lacZ construct in S.
      cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1
      expression by antifungal agents in C. albicans. Consistently, the Candt80/Candt80
      mutant is also more susceptible to antifungal drugs than the wild-type strain.
      Thus, the gene for CaNdt80 may be the first gene among the regulatory factors
      involved in drug resistance in C. albicans whose function has been identified.

PMID- 15561819
TI  - Intranasal interleukin-12 treatment promotes antimicrobial clearance and survival
      in pulmonary Francisella tularensis subsp. novicida infection.
AB  - Francisella tularensis is a highly virulent facultative intracellular bacterium
      and is considered a potential biological warfare agent. Inhalation tularemia can
      lead to the development of bronchopneumonia, which is frequently fatal without
      medical intervention. Treatment strategies that directly target the respiratory
      mucosa may extend the efficacy of therapy, particularly for the medical
      management of acute aerosol exposure. To this end, we describe an intranasal
      (i.n.) strategy for the treatment of pulmonary Francisella infection in mice that
      uses a combinatorial approach with the conventional antibiotic gentamicin and
      interleukin 12 (IL-12). The i.n. administration of IL-12 alone promoted bacterial
      clearance and extended the time to death but did not prevent mortality against
      lethal pulmonary challenge with Francisella tularensis subsp. novicida. However,
      i.n. treatment with gentamicin and IL-12 therapeutically at 8 and 24 h after
      challenge markedly enhanced the rate of survival (70 to 100%) against pulmonary
      infection compared to the rates of survival for animals treated with antibiotic
      alone (17%) or IL-12 alone (0%). A delay in combinatorial therapy over a span of
      4 days progressively decreased the efficacy of this treatment regimen. This
      combinatorial treatment was shown to be highly dependent upon the induction of
      endogenous gamma interferon and may also involve the activation of natural killer
      cells. Together, these findings suggest that IL-12 may be a potent adjunct for
      chemotherapy to enhance drug effectiveness against pulmonary Francisella
      infection.

PMID- 15561820
TI  - In vitro evaluation of the effectiveness of the macrolide rokitamycin and
      chlorpromazine against Acanthamoeba castellanii.
AB  - The present study demonstrates the in vitro effectiveness of the macrolide
      rokitamycin and the phenothiazine compound chlorpromazine against Acanthamoeba
      castellanii. Growth curve evaluations revealed that both drugs inhibit
      trophozoite growth in dose- and time-dependent ways. The effects of both drugs
      when they were used at the MICs at which 100% of isolates are inhibited were
      amoebistatic, but at higher doses they were amoebicidal as well as cysticidal.
      Experiments showed that when rokitamycin was associated with chlorpromazine or
      amphotericin B, rokitamycin enhanced their activities. Furthermore, low doses of
      rokitamycin and chlorpromazine, alone or in combination, blocked the cytopathic
      effect of A. castellanii against WKD cells derived from the human cornea. These
      results may have important significance in the development of new anti
      Acanthamoeba compounds.

PMID- 15561821
TI  - TEM-121, a novel complex mutant of TEM-type beta-lactamase from Enterobacter
      aerogenes.
AB  - Enterobacter aerogenes clinical isolate LOR was resistant to penicillins and
      ceftazidime but susceptible to cefuroxime, cephalothin, cefoxitin, cefotaxime,
      ceftriaxone, and cefepime. PCR and cloning experiments from this strain
      identified a novel TEM-type beta-lactamase (TEM-121) differing by five amino acid
      substitutions from beta-lactamase TEM-2 (Glu104Lys, Arg164Ser, Ala237Thr,
      Glu240Lys, and Arg244Ser) and by only one amino acid change from the extended
      spectrum beta-lactamase (ESBL) TEM-24 (Arg244Ser), with the last substitution
      also being identified in the inhibitor-resistant beta-lactamase IRT-2. Kinetic
      parameters indicated that TEM-121 hydrolyzed ceftazidime and aztreonam (like TEM
      24) and was inhibited weakly by clavulanic acid and strongly by tazobactam. Thus,
      TEM-121 is a novel complex mutant TEM beta-lactamase (CMT-4) combining the
      kinetic properties of an ESBL and an inhibitor-resistant TEM enzyme.

PMID- 15561822
TI  - PnuC and the utilization of the nicotinamide riboside analog 3-aminopyridine in
      Haemophilus influenzae.
AB  - The utilization pathway for the uptake of NAD and nicotinamide riboside was
      previously characterized for Haemophilus influenzae. We now report on the
      cellular location, topology, and substrate specificity of PnuC. pnuC of H.
      influenzae is only distantly related to pnuC of Escherichia coli and Salmonella
      enterica serovar Typhimurium. When E. coli PnuC was expressed in an H. influenzae
      pnuC mutant, it was able to take up only nicotinamide riboside and not
      nicotinamide mononucleotide. Therefore, we postulated that PnuC transporters in
      general possess specificity for nicotinamide riboside. Earlier studies showed
      that 3-aminopyridine derivatives (e.g., 3-aminopyridine adenine dinucleotide) are
      inhibitory for H. influenzae growth. By testing characterized strains with
      mutations in the NAD utilization pathway, we show that 3-aminopyridine riboside
      is inhibitory to H. influenzae and is taken up by the NAD-processing and
      nicotinamide riboside route. 3-Aminopyridine riboside is utilized effectively in
      a pnuC+ background. In addition, we demonstrate that 3-aminopyridine adenine
      dinucleotide resynthesis is produced by NadR. 3-Aminopyridine riboside-resistant
      H. influenzae isolates were characterized, and mutations in nadR could be
      detected. We also tested other species of the family Pasteurellaceae, Pasteurella
      multocida and Actinobacillus actinomycetemcomitans, and found that 3
      aminopyridine riboside does not act as a growth inhibitor; hence, 3-aminopyridine
      riboside represents an anti-infective agent with a very narrow host range.

PMID- 15561823
TI  - Potent and long-acting dimeric inhibitors of influenza virus neuraminidase are
      effective at a once-weekly dosing regimen.
AB  - Dimeric derivatives (compounds 7 to 9) of the influenza virus neuraminidase
      inhibitor zanamivir (compound 2), which have linking groups of 14 to 18 atoms in
      length, are approximately 100-fold more potent inhibitors of influenza virus
      replication in vitro and in vivo than zanamivir. The observed optimum linker
      length of 18 to 22 A, together with observations that the dimers cause
      aggregation of isolated neuraminidase tetramers and whole virus, indicate that
      the dimers benefit from multivalent binding via intertetramer and intervirion
      linkages. The outstanding long-lasting protective activities shown by compounds 8
      and 9 in mouse influenza infectivity experiments and the extremely long residence
      times observed in the lungs of rats suggest that a single low dose of a dimer
      would provide effective treatment and prophylaxis for influenza virus infections.

PMID- 15561824
TI  - Rapid, simple in vivo screen for new drugs active against Mycobacterium
      tuberculosis.
AB  - We evaluated the use of a simple and easy-to-obtain potential marker of
      tuberculosis (TB) drug efficacy, body weight, and correlated weight loss or gain
      with the number of CFU of Mycobacterium tuberculosis in lungs and spleens of
      infected mice. C3H mice were infected intravenously with 10(6) CFU of virulent M.
      tuberculosis H37Rv, and body weight was evaluated for several weeks after
      infection. At day 20, infected untreated mice consistently lost more than 25% of
      their body weight. Chemotherapy with selected orally active anti-TB drugs was
      initiated 7 days following infection and continued for 13 days. Drugs that were
      administered daily by gavage included isoniazid (INH), ethambutol (EMB), rifampin
      (RIF), and moxifloxacin (MXF). At the most effective doses, each of these drugs
      inhibited bacterial growth and abolished infection-induced body weight loss.
      Chemotherapy with 1/10 the standard dose of INH determined in accepted long-term
      murine models of TB also prevented body weight loss, while chemotherapy with 1/10
      the standard dose of RIF did not. With only 2 weeks of chemotherapy, we observed
      a good reverse correlation between CFU in lung or spleen and body weight of mice.
      The simple measurement of weight in TB-infected drug-treated mice required only a
      weight balance, and go/no-go drug efficacy data was available on day 20 without
      the necessity of prolonged drug treatment and long (3 weeks or more) in vitro
      culture times to obtain organ CFU values.

PMID- 15561825
TI  - Detection of CTX-M-type beta-lactamase genes in fecal Escherichia coli isolates
      from healthy children in Bolivia and Peru.
AB  - A survey was carried out from August to November 2002 to evaluate the
      antimicrobial susceptibilities of fecal Escherichia coli isolates from 3,208
      healthy children from four different urban areas of Latin America, two in Bolivia
      (Camiri and Villa Montes) and two in Peru (Yurimaguas and Moyobamba). Ceftriaxone
      resistant E. coli isolates were detected in four children, one from each of the
      areas sampled. The isolates exhibited a multidrug-resistant phenotype, including
      resistance to oxyimino-cephalosporins and aztreonam, and the MICs of ceftazidime
      for the isolates were lower than those of cefotaxime. By PCR and sequencing, the
      bla(CTX-M-2) determinant was detected in three isolates and the bla(CTX-M-15)
      determinant was detected in one isolate (from Peru). The CTX-M-2-producing
      isolates belonged to three different phylogenetic groups (groups A, B2, and D),
      while the CTX-M-15-producing isolate belonged to phylogenetic group D. The
      bla(CTX-M-2) determinants were transferable to E. coli by conjugation, while
      conjugative transfer of the bla(CTX-M-15) determinant was not detectable.
      Plasmids harboring the bla(CTX-M-2) determinant exhibited similar restriction
      profiles, and in all of them the gene was located on a 2.2-kb PstI fragment,
      suggesting a genetic environment similar to that present in In35 and InS21. The
      findings of the present study confirm the widespread distribution of CTX-M-type
      beta-lactamases and underscore the role that commensal E. coli isolates could
      play as a potential reservoir of these clinically relevant resistance
      determinants. This is the first report of CTX-M-type enzymes in Bolivia and Peru
      and also the first report of the detection of CTX-M-15 in Latin America.

PMID- 15561826
TI  - Comparative in vitro activities of linezolid, telithromycin, clarithromycin,
      levofloxacin, moxifloxacin, and four conventional antimycobacterial drugs against
      Mycobacterium kansasii.
AB  - Mycobacterium kansasii is one of the most pathogenic and frequent nontuberculous
      mycobacteria isolated from humans. Patients with adverse drug reactions,
      resistant isolates, or suboptimal response require alternative treatment
      regimens. One hundred forty-eight consecutive clinical isolates of M. kansasii
      were tested for antimicrobial susceptibilities by the BACTEC 460 system (NCCLS)
      with two different inoculation protocols, one conventional and one alternative.
      In the alternative protocol, the inoculum 12B vial was incubated until the growth
      index was between 250 and 500. Four conventional antimycobacterial drugs
      (isoniazid, rifampin, streptomycin, and ethambutol) were studied with standard
      critical concentrations. The in vitro activities of linezolid, telithromycin,
      clarithromycin, levofloxacin, and moxifloxacin were determined by measuring
      radiometric MICs. All isolates tested were identified as M. kansasii genotype I
      and were resistant to isoniazid at a concentration of 0.4 mug/ml. One hundred
      twenty isolates (81.1%) were inhibited by 1 microg of isoniazid per ml. A high
      level of resistance to isoniazid (>10 microg/ml) was observed in six isolates
      (4.1%). Only five strains (3.4%) were resistant to rifampin (>1 microg/ml). All
      isolates studied were susceptible to streptomycin and ethambutol. The MICs at
      which 90% of the isolates were inhibited (in micrograms per milliliter) were as
      follows: linezolid, 1 (range, < or =0.25 to 2); telithromycin, >16 (range, 4 to
      >16); clarithromycin, 0.5 (range, < or =0.03 to 1); levofloxacin, 0.12 (range,
      0.12 to 0.25); and moxifloxacin, 0.06 (range, < or =0.06 to 0.12). The
      susceptibility testing results with both inoculation protocols showed perfect
      correlation. In conclusion, all M. kansasii isolates showed decreased
      susceptibility to isoniazid, but resistance to rifampin was infrequent.
      Quinolones, especially moxifloxacin, were the most active antimicrobial agents
      tested, followed by clarithromycin. Linezolid also showed good activity against
      these microorganisms, but telithromycin's in vitro activity was poor.

PMID- 15561827
TI  - Penicillin-binding protein 2 is essential for expression of high-level vancomycin
      resistance and cell wall synthesis in vancomycin-resistant Staphylococcus aureus
      carrying the enterococcal vanA gene complex.
AB  - A combination of biochemical and genetic experiments were performed in order to
      better understand the mechanism of expression of high-level vancomycin resistance
      in Staphylococcus aureus. The transcription of pbp2 of the highly vancomycin- and
      oxacillin-resistant strain COLVA200 and its mutant derivative with inactivated
      mecA were put under the control of an inducible promoter, and the dependence of
      oxacillin and vancomycin resistance and cell wall composition on the
      concentration of the isopropyl-beta-D-thiogalactopyranoside inducer was
      determined. The results indicate that mecA--the genetic determinant of oxacillin
      resistance--while essential for oxacillin resistance, is not involved with the
      expression of vancomycin resistance. Penicillin binding protein 2A, the protein
      product of mecA, appears to be unable to utilize the depsipeptide cell wall
      precursor produced in the vancomycin-resistant cells for transpeptidation. The
      key penicillin binding protein essential for vancomycin resistance and for the
      synthesis of the abnormally structured cell walls characteristic of vancomycin
      resistant S. aureus (A. Severin, K. Tabei, F. Tenover, M. Chung, N. Clarke, and
      A. Tomasz, J. Biol. Chem. 279:3398-3407, 2004) is penicillin binding protein 2.

PMID- 15561828
TI  - Bloodstream infections due to extended-spectrum beta-lactamase-producing
      Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and
      treatment outcome, with special emphasis on antimicrobial therapy.
AB  - This study was conducted to evaluate risk factors for mortality and treatment
      outcome of bloodstream infections due to extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production
      in stored K. pneumoniae and E. coli blood isolates from Jan 1998 to Dec 2002 was
      phenotypically determined according to NCCLS guidelines and/or the double-disk
      synergy test. A total of 133 patients with ESBL-EK bacteremia, including 66
      patients with ESBL-producing K. pneumoniae and 67 with ESBL-producing E. coli,
      were enrolled. The overall 30-day mortality rate was 25.6% (34 of 133).
      Independent risk factors for mortality were severe sepsis, peritonitis,
      neutropenia, increasing Acute Physiology and Chronic Health Evaluation II score,
      and administration of broad-spectrum cephalosporin as definitive antimicrobial
      therapy (P < 0.05 for each of these risk factors). In 117 of the 133 patients,
      excluding 16 patients who died within 3 days after blood culture sample
      acquisition, the 30-day mortality rates according to definitive antibiotics were
      as follows: carbapenem, 12.9% (8 of 62); ciprofloxacin, 10.3% (3 of 29); and
      others, such as cephalosporin or an aminoglycoside, 26.9% (7 of 26). When
      patients who received appropriate definitive antibiotics, such as carbapenem or
      ciprofloxacin, were evaluated, mortality in patients receiving inappropriate
      empirical antimicrobial therapy was found not to be significantly higher than
      mortality in those receiving appropriate empirical antimicrobial therapy (18.9
      versus 15.5%; P = 0.666). Carbapenem and ciprofloxacin were the most effective
      antibiotics in antimicrobial therapy for ESBL-EK bacteremia. A delay in
      appropriate definitive antimicrobial therapy was not associated with higher
      mortality if antimicrobial therapy was adjusted appropriately according to the
      susceptibility results. Our data suggest that more prudent use of carbapenem as
      empirical antibiotic may be reasonable.

PMID- 15561829
TI  - Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in
      mice.
AB  - It has been documented that sucralfate, a basic aluminum salt, enhances the
      efficacies of antibiotics against Helicobacter pylori, resulting in eradication
      rates comparable to those associated with the use of proton pump inhibitors.
      However, its mechanism of action remains unclear. The aim of the present study
      was to investigate sucralfate's ability to complement antibiotic treatment of H.
      pylori infection in vivo. Four weeks following induced H. pylori infection,
      clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6
      mice for 5 days, both with and without sucralfate or lansoprazole. When
      sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory
      doses for the treatment of H. pylori infection, the bacterial clearance rates
      were comparable to those achieved by treatment with lansoprazole plus those
      antibiotics. The results of pharmacokinetic studies showed that lansoprazole
      delayed gastric clearance and accelerated the absorption of CAM, whereas
      sucralfate suppressed both gastric clearance and absorption. AMPC was
      undetectable in all samples. Scanning electron microscopy with a microscope to
      which a energy dispersive spectrometer was attached revealed that aluminum
      containing aggregated substances coated the mucosa surrounding H. pylori in mice
      receiving sucralfate plus antibiotics, whereas the gastric surface and pits where
      H. pylori had attached were clearly visible in mice receiving lansoprazole plus
      antibiotics. The addition of sucralfate to the antibiotic suspension resulted in
      a more viscous mixture that bound to the H. pylori-infected mucosa and that
      inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate
      delays gastric clearance of CAM and physically captures H. pylori through the
      creation of an adherent mucus, which leads to bacterial clearance.

PMID- 15561830
TI  - In vitro and in vivo activities of novel 6-methylidene penems as beta-lactamase
      inhibitors.
AB  - Novel penem molecules with heterocycle substitutions at the 6 position via a
      methylidene linkage were investigated for their activities and efficacy as beta
      lactamase inhibitors. The concentrations of these molecules that resulted in 50%
      inhibition of enzyme activity were 0.4 to 3.1 nM for the TEM-1 enzyme, 7.8 to 72
      nM for Imi-1, 1.5 to 4.8 nM for AmpC, and 14 to 260 nM for a CcrA metalloenzyme.
      All the inhibitors were more stable than imipenem against hydrolysis by hog and
      human dehydropeptidases. Piperacillin was combined with a constant 4-microg/ml
      concentration of each inhibitor for MIC determinations. The combinations reduced
      piperacillin MICs by 2- to 32-fold for extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli and Klebsiella pneumoniae strains. The MICs for
      piperacillin-resistant (MIC of piperacillin, >64 microg/ml) strains of
      Enterobacter spp., Citrobacter spp., and Serratia spp. were reduced to the level
      of susceptibility (MIC of piperacillin, < or =16 microg/ml) when the drug was
      combined with 4, 2, or 1 microg of these penem inhibitors/ml. Protection against
      acute lethal bacterial infections with class A and C beta-lactamase- and ESBL
      producing organisms in mice was also demonstrated with piperacillin plus
      inhibitor. Median effective doses were reduced by approximately two- to eightfold
      compared to those of piperacillin alone when the drug was combined with the
      various inhibitors at a 4:1 ratio. Pharmacokinetic analysis after intravenous
      administration of the various inhibitors showed mean residence times of 0.1 to
      0.5 h, clearance rates of 15 to 81 ml/min/kg, and volumes of distribution between
      0.4 and 2.5 liters/kg. The novel methylidene penem molecules inhibit both class A
      and class C enzymes and warrant further investigation for potential as
      therapeutic agents when used in combination with a beta-lactam antibiotic.

PMID- 15561831
TI  - Pharmacokinetics and pharmacodynamics of intravenous levofloxacin at 750
      milligrams and various doses of metronidazole in healthy adult subjects.
AB  - The purpose of this investigation was to evaluate the steady-state
      pharmacokinetics, pharmacodynamics, and safety of intravenous levofloxacin at 750
      mg administered once daily combined with three different dosages of intravenous
      metronidazole (500 mg every 8 h [q8h], 1,000 mg q24h, and 1,500 mg q24h).
      Eighteen healthy adult subjects received all three combinations in a randomized,
      crossover fashion. Serial blood and urine samples were collected on the third day
      of each study period. The 24-h areas under the inhibitory (AUIC(0-24)) and
      bactericidal (AUBC(0-24)) curves of these three combination regimens were
      determined against clinical isolates of Bacteroides fragilis, Bacteroides
      thetaiotaomicron, Peptostreptococcus asaccharolyticus, and Escherichia coli. The
      mean concentrations of levofloxacin were not different between study periods and
      were similar to those previously published. The mean (+/- standard deviation)
      areas under the metronidazole plasma concentration-time curve (AUC(0-24)) for
      1,500-mg q24h (338 +/- 105 mg.h/liter) and 500-mg q8h (356 +/- 68 mg.h/liter)
      regimens were not different (P > 0.05), but both were significantly higher than
      the 1,000-mg q24h AUC(0-24) (P < 0.05, 227 +/- 57 mg.h/liter). Mean (+/- standard
      deviation) total body clearance and renal clearance values were similar among the
      500-mg q8h, 1,000-mg q24, and 1,500-mg q24h regimens (62 +/- 7, 67 +/- 13, and 67
      +/- 14 and 11 +/- 3, 12 +/- 2, and 12 +/- 5 ml/min/1.73 m2, respectively).
      Levofloxacin at 750 mg q24h plus metronidazole at 500 mg q8h or 1,500 mg q24h
      resulted in similar AUIC(0-24) and AUBC(0-24) values with one exception: the
      AUIC(0-24) for the 1,500-mg q24h regimen against B. thetaiotamicron was
      significantly higher (P < 0.05) than those of the other regimens. Overall, the
      combination of levofloxacin at 750 mg once daily and metronidazole at 500 mg q8h
      or 1,500 mg q24h appeared to have greater AUIC(0-24) and AUBC(0-24) values than
      did the 1,000-mg q24h regimen. All combination regimens of levofloxacin and
      metronidazole were well tolerated, and no serious drug-related adverse effects
      were reported. The pharmacokinetic, safety, and pharmacodynamic data from our
      study suggest that a once-daily regimen of intravenous levofloxacin at 750 mg and
      metronidazole at 1,500 mg warrants further clinical investigation.

PMID- 15561832
TI  - National surveillance of antimicrobial resistance in Pseudomonas aeruginosa
      isolates obtained from intensive care unit patients from 1993 to 2002.
AB  - Nosocomial infections caused by Pseudomonas aeruginosa in critically ill patients
      are often difficult to treat due to resistance to multiple antimicrobials. The
      purpose of this study was to evaluate antimicrobial resistance among P.
      aeruginosa isolates from intensive care unit patients in the United States from
      1993 to 2002 by using the Intensive Care Unit Surveillance Study database. Over
      the 10-year period, susceptibility of 13,999 nonduplicate isolates of P.
      aeruginosa was analyzed. From 1993 to 2002, nationwide increases in antimicrobial
      resistance were greatest for ciprofloxacin, imipenem, tobramycin, and aztreonam.
      Rates of multidrug resistance (resistance to > or =3 of the following drugs:
      ceftazidime, ciprofloxacin, tobramycin, and imipenem) increased from 4% in 1993
      to 14% in 2002. The lowest dual resistance rates were observed between
      aminoglycosides or fluoroquinolones with piperacillin-tazobactam while the
      highest were for those that included beta-lactams and ciprofloxacin. Ongoing
      surveillance studies are crucial in monitoring antimicrobial susceptibility
      patterns and selecting empirical treatment regimens.

PMID- 15561833
TI  - Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse
      transcriptase confer resistance to nucleoside and nonnucleoside analogs and
      impair virus replication.
AB  - The frequencies of multidrug resistance-associated mutations at codons 145, 151,
      and 69 of the human immunodeficiency virus (HIV) reverse transcriptase (RT) gene
      in strains from a group of 3,595 highly active antiretroviral therapy (HAART)
      experienced patients were 0.22, 2.36, and 0.86%, respectively. Several amino acid
      substitutions different from the recently reported Gln145Met change (S. Paolucci,
      F. Baldanti, M. Tinelli, G. Maga, and G. Gerna, AIDS 17:924-927, 2003) were
      detected at position 145. Thus, amino acid substitutions selected at position 145
      were introduced into the wild-type HIV type 1 (HIV-1) RT gene by site-directed
      mutagenesis, and recombinant HIV strains were assayed for their drug
      susceptibilities. Only Met and Leu substitutions at position 145 of the HIV-1 RT
      conferred multidrug resistance, while other amino acid changes did not. Lower
      levels of replication of the Gln145Met recombinant strain compared with those of
      both Gln151Met and wild-type recombinant strains were observed. In in vitro
      inhibition assays, expression and purification of the recombinant Gln145Met HIV-1
      RT revealed a strong loss of catalytic efficiency of the mutated enzyme, as well
      as significant resistance to both zidovudine and efavirenz. Specific amino acid
      substitutions in the HIV RT nucleotide-binding pocket might affect both
      antiretroviral drug recognition and binding and decrease the level of virus
      replication, possibly by interfering with the enzyme activity. This finding may
      explain the lower frequency of Gln145Met/Leu mutations observed compared with the
      frequencies of Gln151Met/Leu mutations and the insertion at position 69 in HAART
      experienced patients.

PMID- 15561834
TI  - Amoxicillin-clavulanate therapy increases childhood nasal colonization by
      methicillin-susceptible Staphylococcus aureus strains producing high levels of
      penicillinase.
AB  - We examined factors associated with penicillinase production by nasal carriage
      Staphylococcus aureus strains in 648 children aged 3 to 6 years attending 20
      randomly sampled playschools. The children were prospectively monitored for drug
      use and medical events for 6 months and were then screened for S. aureus
      carriage. Isolates were tested for their susceptibility to penicillin G and
      methicillin, and penicillinase production by methicillin-susceptible, penicillin
      resistant strains was quantified. S. aureus was isolated from 166 children
      (25.6%). Exposure to amoxicillin-clavulanate during the previous 3 months was
      associated with higher penicillinase production by penicillin-resistant,
      methicillin-susceptible strains (odds ratio, 3.6; P = 0.03). These results
      suggest that use of the amoxicillin-clavulanate combination could induce a herd
      selection process of S. aureus strains producing higher levels of penicillinase.

PMID- 15561835
TI  - Characterization and molecular analysis of macrolide-resistant Mycoplasma
      pneumoniae clinical isolates obtained in Japan.
AB  - In recent years, Mycoplasma pneumoniae strains that are clinically resistant to
      macrolide antibiotics have occasionally been encountered in Japan. Of 76 strains
      of M. pneumoniae isolated in three different areas in Japan during 2000 to 2003,
      13 strains were erythromycin (ERY) resistant. Of these 13 strains, 12 were highly
      ERY resistant (MIC, > or =256 microg/ml) and 1 was weakly resistant (MIC, 8
      microg/ml). Nucleotide sequencing of domains II and V of 23S rRNA and ribosomal
      proteins L4 and L22, which are associated with ERY resistance, showed that 10
      strains had an A-to-G transition at position 2063 (corresponding to 2058 in
      Escherichia coli numbering), 1 strain showed A-to-C transversion at position
      2063, 1 strain showed an A-to-G transition at position 2064, and the weakly ERY
      resistant strain showed C-to-G transversion at position 2617 (corresponding to
      2611 in E. coli numbering) of domain V. Domain II and ribosomal proteins L4 and
      L22 were not involved in the ERY resistance of these clinical M. pneumoniae
      strains. In addition, by using our established restriction fragment length
      polymorphism technique to detect point mutations of PCR products for domain V of
      the 23S rRNA gene of M. pneumoniae, we found that 23 (24%) of 94 PCR-positive
      oral samples taken from children with respiratory infections showed A2063G
      mutation. These results suggest that ERY-resistant M. pneumoniae infection is not
      unusual in Japan.

PMID- 15561836
TI  - Pharmacokinetics and effects of ribavirin following intraventricular
      administration for treatment of subacute sclerosing panencephalitis.
AB  - Ribavirin is a broad-spectrum antiviral drug with inhibitory activity against
      many RNA viruses, including measles virus. Five patients with subacute sclerosing
      panencephalitis (SSPE) were treated with ribavirin by intraventricular
      administration. Although there were transient side effects attributed to
      ribavirin, such as drowsiness, headache, lip and gingival swelling, and
      conjunctival hyperemia, intraventricular ribavirin therapy was generally safe and
      well tolerated. The cerebrospinal fluid (CSF) ribavirin concentration decreased,
      as described by a monoexponential function, after a single intraventricular dose.
      There was considerable interindividual variability, however, in the peak level
      and half-life. We aimed to adjust the individual dose and frequency of
      intraventricular administration based on the peak level and half-life of
      ribavirin in the CSF in order to maintain the CSF ribavirin concentration at the
      target level. Clinical effectiveness (significant neurologic improvement and/or a
      significant decrease in titers of hemagglutination inhibition antibodies against
      measles virus in CSF) was observed for four of five patients. For these four
      patients, CSF ribavirin concentrations were maintained at a level at which SSPE
      virus replication was almost completely inhibited in vitro and in vivo, whereas
      the concentration was lower in the patient without clinical improvement. These
      results suggest that intraventricular administration of ribavirin is effective
      against SSPE if the CSF ribavirin concentration is maintained at a high level.
      Intraventricular ribavirin therapy should be pursued further for its potential
      use for patients with SSPE and might be applied in the treatment of patients with
      encephalitis caused by other RNA viruses.

PMID- 15561837
TI  - Metabolism of the anti-hepatitis C virus nucleoside beta-D-N4-hydroxycytidine in
      different liver cells.
AB  - Beta-D-N4-hydroxycytidine (NHC) was found to have selective anti-hepatitis C
      virus (HCV) activity in the HCV replicon system (clone A). The intracellular
      metabolism of tritiated NHC was investigated in the HCV replicon system, Huh-7
      cells, HepG2 cells, and primary human hepatocytes. Incubation of cells with 10
      microM radiolabeled NHC demonstrated extensive and rapid phosphorylation in all
      liver cells. Besides the 5'-mono, -di-, and -triphosphate metabolites of NHC,
      other metabolites were characterized. These included cytidine and uridine mono-,
      di-, and triphosphates. UTP was the predominant early metabolite in Huh-7 cells
      and primary human hepatocytes, suggesting deamination of NHC as the primary
      catabolic pathway. The intracellular half-lives of radiolabeled NHC-triphosphate
      and of CTP and UTP derived from NHC incubation in Huh-7 cells were calculated to
      be 3.0 +/- 1.3, 10.4 +/- 3.3, and 13.2 +/- 3.5 h (means +/- standard deviations),
      respectively. Studies using monkey and human whole blood demonstrated more-rapid
      deamination and oxidation in monkey cells than in human cells, suggesting that
      NHC may not persist long enough in plasma to be delivered to liver cells.

PMID- 15561838
TI  - Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation
      of natural resistance to trimethoprim.
AB  - Bacillus anthracis is reported to be naturally resistant to trimethoprim (TMP), a
      drug that inhibits dihydrofolate reductase (DHFR), a key enzyme in the folate
      pathway. A microdilution broth assay established that the MIC of TMP for B.
      anthracis Sterne is >2,048 but < or =4,096 microg/ml. A putative DHFR sequence
      was amplified from B. anthracis Sterne genomic DNA. The PCR product was cloned
      into the Invitrogen pCRT7/CT-TOPO vector, followed by transformation into
      Escherichia coli TOP10F' chemically competent cells. Plasmid DNA from a clone
      showing the correct construct with a thrombin cleavage site attached downstream
      from the terminus of the cloned PCR product was transformed into E. coli BL21
      Star (DE3)pLysS competent cells for expression of the six-histidine-tagged fusion
      protein and purification on a His-Bind resin column. Functionality of the
      purified Sterne recombinant DHFR (Sterne rDHFR) was confirmed in an established
      enzyme assay. The 50% inhibitory concentrations of TMP and methotrexate for the
      Sterne rDHFR were found to be 77,233 and 12.2 nM, respectively. TMP resistance
      was observed with E. coli BL21 Star (DE3)pLysS competent cells transformed with
      the Sterne DHFR gene. Alignment of the amino acid sequence of the Sterne DHFR
      gene revealed 100% homology with various virulent strains of B. anthracis. These
      results confirm the natural resistance of B. anthracis to TMP and clarify that
      the resistance is correlated to a lack of selectivity for the chromosomally
      encoded gene product. These findings will assist in the development of narrow
      spectrum antimicrobial agents for treatment of anthrax.

PMID- 15561839
TI  - Pharmacokinetics of telithromycin in plasma and soft tissues after single-dose
      administration to healthy volunteers.
AB  - By use of microdialysis we assessed the concentrations of telithromycin in muscle
      and adipose tissue to test its ability to penetrate soft tissues. The ratios of
      the area under the concentration-versus-time curve from 0 to 24 h to the MIC
      indicated that free concentrations of telithromycin in tissue and plasma might be
      effective against Streptococcus pyogenes but not against staphylococci and human
      and animal bite pathogens.

PMID- 15561840
TI  - Molecular characterization of a beta-lactamase gene, blaGIM-1, encoding a new
      subclass of metallo-beta-lactamase.
AB  - As part of the SENTRY Antimicrobial Surveillance Program in 2002, five multidrug
      resistant Pseudomonas aeruginosa clinical isolates were detected with metallo
      beta-lactamase (MbetaL) activity. The isolates were recovered from different
      patients in a medical center located in Dusseldorf, Germany. The resistant
      determinant was isolated amplifying the region between the integrase and the
      aacA4 gene cassette. Sequencing revealed a novel MbetaL gene, designated bla(GIM
      1). Additional analysis showed that GIM-1, comprising 250 amino acids and with a
      pI value of 5.4, differs in its primary sequence from that described for IMP,
      VIM, and SPM-1 enzymes by 39 to 43%, 28 to 31%, and 28%, respectively. The enzyme
      possesses unique amino acids within the major consensus sequence (HXHXD) of the
      MbetaL family. Kinetics analysis revealed that GIM-1 has no clear preference for
      any substrate and did not hydrolyze azlocillin, aztreonam, and the serine-beta
      lactamase inhibitors. bla(GIM-1) was found on a 22-kb nontransferable plasmid.
      The new MbetaL gene was embedded in the first position of a 6-kb class 1
      integron, In77, with distinct features, including an aacA4 cassette downstream of
      the MbetaL gene that appeared to be truncated with bla(GIM-1). The aacA4 was
      followed by an aadA1 gene cassette that was interrupted by a copy of the IS1394.
      This integron also carried an oxacillinase gene, bla(OXA-2), before the 3'-CS
      region. GIM-1 appears to be a unique MbetaL, which is located in a distinct
      integron structure, and represents the fourth subclass of mobile MbetaL enzymes
      to be characterized.

PMID- 15561841
TI  - A radio frequency electric current enhances antibiotic efficacy against bacterial
      biofilms.
AB  - Bacterial biofilms are notably resistant to antibiotic prophylaxis. The
      concentration of antibiotic necessary to significantly reduce the number of
      bacteria in the biofilm matrix can be several hundred times the MIC for the same
      bacteria in a planktonic phase. It has been observed that the addition of a weak
      continuous direct electric current to the liquid surrounding the biofilm can
      dramatically increase the efficacy of the antibiotic. This phenomenon, known as
      the bioelectric effect, has only been partially elucidated, and it is not certain
      that the electrical parameters are optimal. We confirm here the bioelectric
      effect for Escherichia coli biofilms treated with gentamicin and with
      oxytetracycline, and we report a new bioelectric effect with a radio frequency
      alternating electric current (10 MHz) instead of the usual direct current. None
      of the proposed explanations (transport of ions within the biofilm, production of
      additional biocides by electrolysis, etc.) of the direct current bioelectric
      effect are applicable to the radio frequency bioelectric effect. We suggest that
      this new phenomenon may be due to a specific action of the radio frequency
      electromagnetic field upon the polar parts of the molecules forming the biofilm
      matrix.

PMID- 15561842
TI  - Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin,
      vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin,
      in an in vitro pharmacodynamic model.
AB  - We evaluated the impact of high (9.5 log10 CFU/g) and moderate (5.5 log10 CFU/g)
      inocula of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and
      MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and
      daptomycin, alone and in combination with gentamicin in an in vitro
      pharmacodynamic model with simulated endocardial vegetations over 72 h. Human
      therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and
      gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only),
      vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01)
      bactericidal (99.9% kill) activities (decreases of 3.34 +/- 1.1, 3.28 +/- 0.4,
      and 3.34 +/- 0.8 log10 CFU/g, respectively). Bactericidal activity was
      demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin.
      Linezolid demonstrated bacteriostatic activity over the course of the study
      period. At a high inoculum, daptomycin exhibited bactericidal activity against
      both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 +/- 0.10 log10 CFU/g).
      Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not
      achieve bactericidal activity throughout the 72-h experiment. The addition of
      gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and
      48 h for nafcillin (MSSA only) (P = 0.01). The addition of gentamicin did not
      improve the activity of vancomycin or linezolid for either isolate for the 72-h
      period. Overall, high-inoculum Staphylococcus aureus had a significant impact on
      the activities of nafcillin and vancomycin. In contrast, daptomycin was affected
      minimally and linezolid was not affected by inoculum.

PMID- 15561843
TI  - Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived
      proteinases.
AB  - Cathelicidin LL-37 is one of the few human bactericidal peptides with potent
      antistaphylococcal activity. In this study we examined the susceptibility of LL
      37 to proteolytic degradation by two major proteinases produced by Staphylococcus
      aureus, a metalloproteinase (aureolysin) and a glutamylendopeptidase (V8
      protease). We found that aureolysin cleaved and inactivated LL-37 in a time- and
      concentration-dependent manner. Analysis of the generated fragments by mass
      spectroscopy revealed that the initial cleavage of LL-37 by aureolysin occurred
      between the Arg19-Ile20, Arg23-Ile24, and Leu31-Val32 peptide bonds, instantly
      annihilating the antibacterial activity of LL-37. In contrast, the V8 proteinase
      hydrolyzed efficiently only the Glu16-Phe17 peptide bond, rendering the C
      terminal fragment refractory to further degradation. This fragment (termed LL-17
      37) displayed antibacterial activity against S. aureus at a molar level similar
      to that of the full-length LL-37 peptide, indicating that the antibacterial
      activity of LL-37 resides in the C-terminal region. In keeping with LL-37
      degradation by aureolysin, S. aureus strains that produce significant amounts of
      this metalloprotease were found to be less susceptible to LL-17-37 than strains
      expressing no aureolysin activity. Taken together, these data suggest that
      aureolysin production by S. aureus contributes to the resistance of this pathogen
      to the innate immune system of humans mediated by LL-37.

PMID- 15561844
TI  - TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor
      active against nonnucleoside reverse transcriptase inhibitor-resistant human
      immunodeficiency virus type 1.
AB  - Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent inhibitors of
      human immunodeficiency virus type 1 (HIV-1); however, currently marketed NNRTIs
      rapidly select resistant virus, and cross-resistance within the class is
      extensive. A parallel screening strategy was applied to test candidates from a
      series of diarylpyrimidines against wild-type and resistant HIV strains carrying
      clinically relevant mutations. Serum protein binding and metabolic stability were
      addressed early in the selection process. The emerging clinical candidate,
      TMC125, was highly active against wild-type HIV-1 (50% effective concentration
      [EC50] = 1.4 to 4.8 nM) and showed some activity against HIV-2 (EC50 = 3.5
      microM). TMC125 also inhibited a series of HIV-1 group M subtypes and circulating
      recombinant forms and a group O virus. Incubation of TMC125 with human liver
      microsomal fractions suggested good metabolic stability (15% decrease in drug
      concentration and 7% decrease in antiviral activity after 120 min). Although
      TMC125 is highly protein bound, its antiviral effect was not reduced by the
      presence of 45 mg of human serum albumin/ml, 1 mg of alpha1-acid glycoprotein/ml,
      or 50% human serum. In an initial screen for activity against a panel of 25
      viruses carrying single and double reverse transcriptase amino acid substitutions
      associated with NNRTI resistance, the EC50 of TMC125 was <5 nM for 19 viruses,
      including the double mutants K101E+K103N and K103N+Y181C. TMC125 also retained
      activity (EC50 < 100 nM) against 97% of 1,081 recent clinically derived
      recombinant viruses resistant to at least one of the currently marketed NNRTIs.
      TMC125 is a potent next generation NNRTI, with the potential for use in
      individuals infected with NNRTI-resistant virus.

PMID- 15561845
TI  - Clinically relevant interpretation of genotype and relationship to plasma drug
      concentrations for resistance to saquinavir-ritonavir in human immunodeficiency
      virus type 1 protease inhibitor-experienced patients.
AB  - It has been shown that virological protease inhibitor (PI) resistance mutations
      present at the initiation of saquinavir (SQV) plus ritonavir (RTV) therapy in PI
      experienced patients are the strongest predictors of virological response. But
      most of the current resistance algorithms are adapted for unboosted SQV regimens.
      We applied a stepwise methodology for the development and validation of a
      clinically relevant genotypic resistance score for an SQV (800 mg twice per day
      [b.i.d.]) plus RTV (100 mg b.i.d.)-containing regimen. PI-experienced patients
      treated by this regimen achieved a human immunodeficiency virus plasma viral load
      (VL) of <200 copies/ml at months 3 to 5 for 41.7% of subjects. Adjusted in a
      multivariate analysis, taking into account all the confounding factors, such as
      the nucleoside used, five mutations were combined in a resistance score
      associated with a reduced virological response to an SQV-plus-RTV regimen: L24I,
      I62V, V82A/F/T/S, I84V, and L90IM. Patients with isolates harboring 0 to 1
      mutation among the score achieved -2.20 log10 and -1.23 log10 copies/ml of VL
      reduction, respectively, while it was -0.27 log10 copies/ml for those with at
      least two mutations, classifying the isolates as "no evidence of resistance" (0
      or 1 mutation) or "resistance " (> or =2 mutations). The minimum concentration in
      plasma (Cmin) of SQV alone was not associated with the virological response.
      However, the combination of the SQV Cmin and the genotypic score, expressed as
      the genotypic inhibitory quotient, was predictive of the virological response,
      suggesting that the interpretation of SQV concentrations in plasma should be done
      only in the context of the resistance index provided by viral genotype for PI
      experienced patients.

PMID- 15561846
TI  - Integron carrying a novel metallo-beta-lactamase gene, blaIMP-16, and a fused
      form of aminoglycoside-resistant gene aac(6')-30/aac(6')-Ib': report from the
      SENTRY Antimicrobial Surveillance Program.
AB  - Since January 2002 Pseudomonas sp. strains resistant to carbapenems and
      ceftazidime have been routinely screened as part of the SENTRY Antimicrobial
      Surveillance Program for metallo-beta-lactamase production, and their resistance
      determinants have been analyzed. Pseudomonas aeruginosa index strain 101-4704,
      which harbors a novel bla(IMP) variant, bla(IMP-16), was isolated in April 2002
      from a 60-year-old man in Brasilia, Brazil. bla(IMP-16) was found on the
      chromosome of the P. aeruginosa index strain, and the deduced amino acid sequence
      (IMP-16) showed the greatest identities to IMP-11 (90.3%) and IMP-8 (89.5%).
      Sequence analysis revealed that bla(IMP-16) was associated with a class 1
      integron, which also encoded aminoglycoside-modifying enzymes. Downstream of
      bla(IMP-16) resided an open reading frame, which consisted of a new
      aminoglycoside-modifying gene, namely, aac(6')-30, which was fused with aac(6')
      Ib'. The amino acid sequence of the aac(6')-30 putative protein showed the most
      identity (52.7%) to the sequence of AAC(6')-29b described previously. The fourth
      gene cassette constituted aadA1. The steady-state kinetics of IMP-16 demonstrated
      that the enzyme preferred cephalosporins and carbapenems to penicillins. The main
      functional difference observed among the kinetic values for IMP-16 compared to
      those for other IMPs was a lack of cefoxitin hydrolysis and a lower kcat/Km value
      for imipenem (0.36 microM(-1) . s(-1)). This report further emphasizes the spread
      of metallo-beta-lactamase genes and their close association with various
      aminoglycoside resistance genes.

PMID- 15561847
TI  - Chalcomycin biosynthesis gene cluster from Streptomyces bikiniensis: novel
      features of an unusual ketolide produced through expression of the chm polyketide
      synthase in Streptomyces fradiae.
AB  - Chalcomycin, a 16-membered macrolide antibiotic made by the bacterium
      Streptomyces bikiniensis, contains a 2,3-trans double bond and the neutral sugar
      D-chalcose in place of the amino sugar mycaminose found in most other 16-membered
      macrolides. Degenerate polyketide synthase (PKS)-specific primers were used to
      amplify DNA fragments from S. bikiniensis with very high identity to a unique
      ketosynthase domain of the tylosin PKS. The resulting amplimers were used to
      identify two overlapping cosmids encompassing the chm PKS. Sequencing revealed a
      contiguous segment of >60 kb carrying 25 putative genes for biosynthesis of the
      polyketide backbone, the two deoxysugars, and enzymes involved in modification of
      precursors of chalcomycin or resistance to it. The chm PKS lacks the
      ketoreductase and dehydratase domains in the seventh module expected to produce
      the 2,3-double bond in chalcomycin. Expression of PKS in the heterologous host
      Streptomyces fradiae, from which the tyl genes encoding the PKS had been removed,
      resulted in production of at least one novel compound, characterized as a 3-keto
      16-membered macrolactone in equilibrium with its 3-trans enol tautomer and
      containing the sugar mycaminose at the C-5 position, in agreement with the
      structure predicted on the basis of the domain organization of the chm PKS. The
      production of a 3-keto macrolide from the chm PKS indicates that a discrete set
      of enzymes is responsible for the introduction of the 2,3-trans double bond in
      chalcomycin. From comparisons of the open reading frames to sequences in
      databases, a pathway for the synthesis of nucleoside diphosphate-D-chalcose was
      proposed.

PMID- 15561848
TI  - n-6 polyunsaturated fatty acids enhance the activities of ceftazidime and
      amikacin in experimental sepsis caused by multidrug-resistant Pseudomonas
      aeruginosa.
AB  - Recent in vitro and ex vivo studies disclosed an enhancement of the activity of
      antimicrobials on multidrug-resistant Pseudomonas aeruginosa by n-6
      polyunsaturated fatty acids (PUFAS); therefore their effect was evaluated in
      experimental sepsis in 60 rabbits. Solutions of gamma-linolenic acid (GLA) and
      arachidonic acid (AA) were administered intravenously with ceftazidime and
      amikacin in rabbits with sepsis caused by one multidrug-resistant isolate.
      Therapy was started after bacterial challenge in five groups comprising 12
      animals in each group: A, normal saline; B, antimicrobials; C, 99% ethanol and
      antimicrobials; D, GLA and antimicrobials; and E, AA and antimicrobials. Blood
      was sampled for the estimation of levels of endotoxins in serum
      (lipopolysaccharide), leukocytes, tumor necrosis factor alpha (TNF-alpha) and
      antimicrobials. Animals were sacrificed 210 min after bacterial challenge for
      tissue cultures. All animals had considerable endotoxemia and evolved leukopenia.
      The number of viable cells in blood, lung, and mesenteric lymph nodes was
      significantly reduced in groups D and E compared to that in other groups. Levels
      of antimicrobials in serum were inadequate to achieve bacterial killing due to
      the level of resistance. n-6 PUFAs did not influence TNF-alpha. It is concluded
      that intravenous coadministration of n-6 PUFAs and antimicrobials enhanced
      antimicrobial bacterial killing in experimental sepsis caused by multidrug
      resistant P. aeruginosa.

PMID- 15561849
TI  - Pharmacodynamic profiling of piperacillin in the presence of tazobactam in
      patients through the use of population pharmacokinetic models and Monte Carlo
      simulation.
AB  - The primary objectives of this analysis were to determine which pharmacokinetic
      model most accurately describes the elimination pathways for piperacillin in the
      presence of tazobactam through population pharmacokinetic modeling and to
      characterize its pharmacodynamic profile. Once the optimal pharmacokinetic model
      was identified, Monte Carlo simulation of 10,000 subjects with ADAPT II was
      performed to estimate the probability of attaining a target free-piperacillin
      concentration greater than the MIC for 50% of the dosing interval for 3.375 g
      every 6 h or every 4 h given as a 0.5-h infusion at each MIC between 0.25 and 32
      microg/ml. In the population pharmacokinetic analysis, measurements of bias and
      precision, observed-predicted plots, and r2 values were highly acceptable for all
      three models and all three models were appropriate candidates for the Monte Carlo
      simulation evaluation. Visual comparison of the distribution of the piperacillin
      concentrations at the pharmacodynamic endpoint--h 3 concentrations of a 6-h
      dosing interval--between the simulated populations and raw data revealed that the
      linear model was most reflective of the raw data at the pharmacodynamic endpoint,
      and the linear model was therefore selected for the target attainment analysis.
      In the target attainment analysis, administration of 3 g of piperacillin every 6
      h resulted in a robust target attainment rate that exceeded 95% for MICs of < or
      =8 mg/liter. The 4-h piperacillin administration interval had a superior
      pharmacodynamic profile and provided target attainment rates exceeding 95% for
      MICs of < or =16 mg/liter. This study indicates that piperacillin-tazobactam
      should have utility for empirical therapy of hospital-onset infections.

PMID- 15561850
TI  - Antibacterial activity of a competence-stimulating peptide in experimental sepsis
      caused by Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer
      autoinducer peptide pheromone (competence-stimulating peptide [CSP]) for the
      control of competence for genetic transformation. Due to previous work linking
      CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect
      on virulence. Our data demonstrate a significant increase in the rates of
      survival of mice, reductions of blood S. pneumoniae counts, and prolonged times
      to death for mice treated with CSP. In vitro the dose of CSP used in the animal
      model produced a transitory inhibition of growth. When a mutant with a mutation
      in the CSP sensor histidine kinase was assayed, no bacteriostatic phenotype was
      detected in vitro and no change in disease outcome was observed in vivo. The data
      demonstrate that CSP, which induces in vitro a temporary growth arrest through
      stimulation of its cognate histidine kinase receptor, is able to block systemic
      disease in mice. This therapeutic effect is novel, in that the drug-like effect
      is obtained by stimulation, rather than inhibition, of a bacterial drug target.

PMID- 15561851
TI  - Evolution of ciprofloxacin-resistant Staphylococcus aureus in in vitro
      pharmacokinetic environments.
AB  - The development of novel antibacterial agents is decreasing despite increasing
      resistance to presently available agents among common pathogens. Insights into
      relationships between pharmacodynamics and resistance may provide ways to
      optimize the use of existing agents. The evolution of resistance was examined in
      two ciprofloxacin-susceptible Staphylococcus aureus strains exposed to in vitro
      simulated clinical and experimental ciprofloxacin pharmacokinetic profiles for 96
      h. As the average steady-state concentration (C(avg ss)) increased, the rate of
      killing approached a maximum, and the rate of regrowth decreased. The enrichment
      of subpopulations with mutations in grlA and low-level ciprofloxacin resistance
      also varied depending on the pharmacokinetic environment. A regimen producing
      values for C(avg ss) slightly above the MIC selected resistant variants with grlA
      mutations that did not evolve to higher levels of resistance. Clinical regimens
      which provided values for C(avg ss) intermediate to the MIC and mutant prevention
      concentration (MPC) resulted in the emergence of subpopulations with gyrA
      mutations and higher levels of resistance. A regimen producing values for C(avg
      ss) close to the MPC selected grlA mutants, but the appearance of subpopulations
      with higher levels of resistance was diminished. A regimen designed to maintain
      ciprofloxacin concentrations entirely above the MPC appeared to eradicate low
      level resistant variants in the inoculum and prevent the emergence of higher
      levels of resistance. There was no relationship between the time that
      ciprofloxacin concentrations remained between the MIC and the MPC and the degree
      of resistance or the presence or type of ciprofloxacin-resistance mutations that
      appeared in grlA or gyrA. Regimens designed to eradicate low-level resistant
      variants in S. aureus populations may prevent the emergence of higher levels of
      fluoroquinolone resistance.

PMID- 15561852
TI  - Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models
      for cytomegalovirus infections.
AB  - We reported previously that purine 2-(hydroxymethyl)methylenecyclopropane analogs
      have good activity against cytomegalovirus infection. A second-generation analog,
      (Z)-9-[[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl]guanine (ZSM-I-62,
      cyclopropavir [CPV]), has particularly good activity against murine and human
      cytomegaloviruses (MCMV and HCMV) in vitro. To determine the oral activity of
      this compound in vivo, BALB/c or severe combined immunodeficient (SCID) mice
      infected with MCMV and two models using SCID mice implanted with human fetal
      tissue and subsequently infected with HCMV were used. In MCMV-infected normal
      mice, CPV at 10 mg/kg of body weight was highly effective in preventing mortality
      when administered at 24, 48, or 72 h post-viral inoculation and reduced titers of
      virus in tissues of SCID mice by 2 to 5 log10. In one HCMV model, human fetal
      retinal tissue was implanted into the anterior chamber of the mouse eye and
      inoculated with the Toledo strain of HCMV, and in the second, human fetal thymus
      and liver tissues were implanted under the kidney capsule of mice and then
      inoculated with HCMV. In general, replication of HCMV in both types of implant
      tissue increased from 7 through 21 to 28 days and then gradually decreased to
      undetectable levels by 8 weeks postinfection. Oral treatment with 45 or 15 mg of
      CPV/kg initiated 24 h after infection was highly effective in reducing
      replication to undetectable levels in both models and was generally more
      effective than ganciclovir. These data indicate that the methylenecyclopropane
      analog, CPV, was highly efficacious in these four animal models and should be
      evaluated for use in HCMV infections in humans.

PMID- 15561853
TI  - Antistaphylococcal activity of WCK 771, a tricyclic fluoroquinolone, in animal
      infection models.
AB  - WCK 771, the arginine salt of S-(-)-nadifloxacin, was evaluated in animal models
      of staphylococcal infection and in vitro. For 302 methicillin-susceptible strains
      the MIC at which 50% of isolates are inhibited (MIC50) and the MIC90 of WCK 771
      were 0.03 and 0.03 microg/ml, respectively, and for 198 methicillin-resistant
      strains the MIC50 and the MIC90 were 0.5 and 1.0 microg/ml, respectively. All
      methicillin-susceptible staphylococci were quinolone susceptible, and almost all
      methicillin-resistant staphylococci were quinolone resistant. WCK 771 was more
      potent than moxifloxacin, trovafloxacin, levofloxacin, and ciprofloxacin and had
      potency comparable to that of clinafloxacin. Only WCK 771 and clinafloxacin
      demonstrated strong potencies against vancomycin-intermediate Staphylococcus
      aureus strains (MICs = 1 microg/ml). WCK 771 is not a substrate of the NorA pump,
      as evident from the lack of an effect of reserpine on the MICs and similar
      protective doses against infections caused by efflux-positive and -negative
      staphylococci. WCK 771 was effective by both the oral and the subcutaneous routes
      in mice infected intraperitoneally with quinolone-susceptible methicillin
      susceptible S. aureus (MSSA) strains. For infections caused by quinolone
      resistant methicillin-resistant S. aureus (MRSA) strains, the activity of WCK 771
      administered subcutaneously was superior to those of trovafloxacin and
      sparfloxacin, with a 50% effective dose range of 27.8 to 46.8 mg/kg of body
      weight. The activity of WCK 771 was superior to those of moxifloxacin,
      vancomycin, and linezolid in a mouse cellulitis model of infection caused by one
      MSSA and two MRSA strains, with effective doses of 2.5 and 5 mg/kg for the MSSA
      strain and 10-fold higher effective doses for MRSA strains. WCK 771, like
      vancomycin and linezolid, eradicated MRSA from mouse liver, spleen, kidney, and
      lung when it was administered subcutaneously at a dose of 50 mg/kg for four
      doses. These studies have demonstrated the effectiveness of WCK 771, administered
      orally and parenterally, for the treatment of diverse staphylococcal infections
      in mice, including those caused by quinolone-resistant strains.

PMID- 15561854
TI  - Derivatives of a vancomycin-resistant Staphylococcus aureus strain isolated at
      Hershey Medical Center.
AB  - Antimicrobial susceptibilities and genetic relatedness of the vancomycin
      resistant Staphylococcus aureus strain (VRSA) isolated at Hershey, Pa. (VRSA
      Hershey), and its vancomycin-susceptible and high-level-resistant derivatives
      were studied and compared to 32 methicillin-resistant S. aureus strains (MRSA)
      isolated from patients and medical staff in contact with the VRSA patient.
      Derivatives of VRSA were obtained by subculturing six VRSA colonies from the
      original culture with or without vancomycin. Ten days of drug-free subculture
      caused the loss of vanA in two vancomycin-susceptible derivatives for which
      vancomycin MICs were 1 to 4 microg/ml. Multistep selection of three VRSA clones
      with vancomycin for 10 days increased vancomycin MICs from 32 to 1,024 to 2,048
      microg/ml. MICs of teicoplanin, dalbavancin, and oritavancin were also increased
      from 4, 0.5, and 0.12 to 64, 1, and 32 microg/ml, respectively. Pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing analysis indicated that
      VRSA Hershey was the vanA-acquired variety of a common MRSA clone in our hospital
      with sequence type 5 (ST5). Three of five vancomycin-intermediate S. aureus
      strains tested from geographically different areas were also ST5, and the
      Michigan VRSA was ST371, a one-allele variant of ST5. Derivatives of VRSA Hershey
      had differences in PFGE profiles and the size of SmaI fragment that carries the
      vanA gene cluster, indicating instability of this cluster in VRSA Hershey.
      However induction with vancomycin increased glycopeptide MICs and stabilized the
      resistance.

PMID- 15561855
TI  - Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with
      community-acquired respiratory tract infections.
AB  - Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone
      currently under study for the treatment of community-acquired respiratory tract
      infections. This analysis assessed garenoxacin population pharmacokinetics and
      exposure-response relationships for safety (adverse effects [AE]) and
      antimicrobial activity (clinical cure and bacteriologic eradication of
      Streptococcus pneumoniae and the grouping of Haemophilus influenzae, Haemophilus
      parainfluenzae, and Moraxella catarrhalis). Data were obtained from three phase
      II clinical trials of garenoxacin administered orally as 400 mg once daily for 5
      to 10 days for the treatment of community-acquired pneumonia, acute exacerbation
      of chronic bronchitis, and sinusitis. Samples were taken from each patient before
      drug administration, 2 h following administration of the first dose, and on the
      day 3 to 5 visit. Individual Bayesian estimates of the fu (fraction unbound), the
      Cmax, and the fu for the area under the concentration-time curve from 0 to 24 h
      (fu AUC(0-24)) were calculated as measurements of drug exposure by using an ex
      vivo assessment of average protein binding. Regression analysis was performed to
      examine the following relationships: treatment-emergent AE incidence and AUC(0
      24), Cmax, or patient factors; clinical response or bacterial eradication and
      drug exposure (fu Cmax/MIC, fu AUC(0-24)/MIC, and other exposure covariates); or
      disease and patient factors. Garenoxacin pharmacokinetics were described by a one
      compartment model with first-order absorption and elimination. Clearance was
      dependent on creatinine clearance, ideal body weight, age, obesity, and
      concomitant use of pseudoephedrine. The volume of distribution was dependent on
      weight and gender. Patients with mild or moderate renal dysfunction had, on
      average, approximately a 16 or 26% decrease in clearance, respectively, compared
      to patients of the same gender and obesity classification with normal renal
      function. AE occurrence was not related to garenoxacin exposure. Overall,
      clinical cure and bacterial eradication rates were 91 and 90%, respectively, for
      S. pneumoniae and 93 and 92%, respectively, for the grouping of H. influenzae, H.
      parainfluenzae, and M. catarrhalis. The fu AUC(0-24)/MIC ratios were high (>90%
      were >200), and none of the pharmacokinetic-pharmacodynamic exposure measurements
      indexed to the MIC or other factors were significant predictors of clinical or
      bacteriologic response. Garenoxacin clearance was primarily related to creatinine
      clearance and ideal body weight. Although garenoxacin exposure was approximately
      25% higher for patients with moderate renal dysfunction, this increase does not
      appear to be clinically significant as exposures in this patient population were
      not significant predictors of AE occurrence. Garenoxacin exposures were at the
      upper end of the exposure-response curves for measurements of antimicrobial
      activity, suggesting that 400 mg of garenoxacin once daily is a safe and adequate
      dose for the treatment of the specified community-acquired respiratory tract
      infections.

PMID- 15561856
TI  - Biochemical characterization of the THIN-B metallo-beta-lactamase of
      Janthinobacterium lividum.
AB  - The THIN-B metallo-beta-lactamase, a subclass B3 enzyme produced by the
      environmental species Janthinobacterium lividum, was overproduced in Escherichia
      coli by means of a T7-based expression system. The enzyme was purified (>95%) by
      two ion-exchange chromatography steps and subjected to biochemical analysis. The
      native THIN-B enzyme is a monomeric protein of 31 kDa. It exhibits the highest
      catalytic efficiencies with carbapenem substrates and cephalosporins, except for
      cephaloridine, which acts as a poor inactivator. Individual rate constants for
      inactivation by chelators were measured, suggesting that inactivation occurred by
      a mechanism involving formation of a ternary complex.

PMID- 15561857
TI  - Combination of a hepatitis C virus NS3-NS4A protease inhibitor and alpha
      interferon synergistically inhibits viral RNA replication and facilitates viral
      RNA clearance in replicon cells.
AB  - The present standard of care for hepatitis C virus (HCV) infection is pegylated
      alpha interferon (IFN-alpha) in combination with ribavirin. However, specific
      antivirals such as HCV NS3-NS4A protease inhibitors are now in clinical
      development, and these agents can potentially be used in combination with the
      present treatments. Therefore, it is important to investigate the potential
      benefits or adverse effects of these new combinations by using available in vitro
      HCV culture systems first. In the present study we demonstrate that the
      combination of a specific HCV NS3-NS4A protease inhibitor and IFN-alpha
      synergistically inhibits HCV RNA replication in replicon cells, with little or no
      increase in cytotoxicity. Furthermore, the benefit of the combination was
      sustained over time, such that a greater than 3-log reduction in HCV RNA levels
      was achieved following 9 days of treatment. The viral RNA appeared to be cleared
      from the replicon cells after 14 days of treatment, and no viral RNA rebound was
      observed upon withdrawal of the inhibitors. In each case, the antiviral effects
      obtained with higher concentrations of either the protease inhibitor alone or IFN
      alpha alone can be achieved by a combination of both agents at lower
      concentrations, which may potentially reduce the risk of possible adverse effects
      associated with high doses of either agent.

PMID- 15561858
TI  - Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A
      beta-lactamase, KPC-3, in a New York Medical Center.
AB  - From April 2000 to April 2001, 24 patients in intensive care units at Tisch
      Hospital, New York, N.Y., were infected or colonized by carbapenem-resistant
      Klebsiella pneumoniae. Pulsed-field gel electrophoresis identified a predominant
      outbreak strain, but other resistant strains were also recovered. Three
      representatives of the outbreak strain from separate patients were studied in
      detail. All were resistant or had reduced susceptibility to imipenem, meropenem,
      ceftazidime, piperacillin-tazobactam, and gentamicin but remained fully
      susceptible to tetracycline. PCR amplified a blaKPC allele encoding a novel
      variant, KPC-3, with a His(272)-->Tyr substitution not found in KPC-2; other
      carbapenemase genes were absent. In the outbreak strain, KPC-3 was encoded by a
      75-kb plasmid, which was transferred in vitro by electroporation and conjugation.
      The isolates lacked the OmpK35 porin but expressed OmpK36, implying reduced
      permeability as a cofactor in resistance. This is the third KPC carbapenem
      hydrolyzing beta-lactamase variant to have been reported in members of the
      Enterobacteriaceae, with others reported from the East Coast of the United
      States. Although producers of these enzymes remain rare, the progress of this
      enzyme group merits monitoring.

PMID- 15561859
TI  - Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects
      susceptibility to moenomycin, as well as vancomycin, gentamicin, and
      antimicrobial peptides, in Staphylococcus aureus.
AB  - An association between moenomycin resistance and vancomycin intermediate
      resistance in Staphylococcus aureus was demonstrated previously. Thus, to
      elucidate the mechanism of vancomycin intermediate resistance, we searched for
      factors contributing to moenomycin resistance. Random Tn551 insertional
      mutagenesis of methicillin-resistant S. aureus strain COL yielded three mutants
      with decreased susceptibilities to moenomycin. Correspondingly, these mutants
      also exhibited slightly decreased susceptibilities to vancomycin. Genetic
      analysis revealed that two of the mutants had Tn551 insertions in the fmtC (mprF)
      gene, which is associated with the synthesis of lysyl-phosphatidylglycerol. The
      third Tn551 insertion was located in the lysC gene, which is involved in the
      biosynthesis of lysine from aspartic acid. Consequently, mutations in both of
      these loci reduced the lysyl-phosphatidylglycerol content in the cell membrane,
      giving it a more negative net charge. The positively charged antibiotic
      gentamicin and cationic antimicrobial peptides such as beta-defensins and CAP18
      were more effective against the mutants. The levels of moenomycin and vancomycin
      binding to intact cells was also greater in the mutants than in the wild type,
      while the binding affinity was not altered when cells boiled in sodium dodecyl
      sulfate were used, indicating that both agents had higher affinities for the
      negatively charged membranes of the mutants. Therefore, the membrane charge of S.
      aureus appears to influence the efficacies of moenomycin, vancomycin, and other
      cationic antimicrobial agents.

PMID- 15561860
TI  - Liposomal nystatin in patients with invasive aspergillosis refractory to or
      intolerant of amphotericin B.
AB  - We assessed the activity and safety of liposomal nystatin, a broad-spectrum
      antifungal agent, for invasive aspergillosis in patients refractory to or
      intolerant of amphotericin B. Thirty-three patients were enrolled, received at
      least one dose of the study drug, and were evaluable for safety. Twenty-six
      patients had confirmed probable or definite aspergillosis and were fully
      eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic
      stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory
      to previous amphotericin B (92.3%). The median duration of previous amphotericin
      B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3
      cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4
      mg/kg of body weight/day. Twenty-five patients were evaluable for response: a
      complete response was achieved for one patient, and a partial response was
      achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence
      interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during
      therapy or within 1 month after the end of therapy. The primary cause of death
      was invasive aspergillosis for nine patients and underlying malignancy for eight
      patients. The most frequent side effects included chills, shivering, and fever,
      leading to discontinuation of therapy for two patients. Grade 1 decline in renal
      function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13
      (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy
      of invasive aspergillosis. Infusion-related adverse events have been observed
      frequently.

PMID- 15561861
TI  - Novel nonnucleoside inhibitor of hepatitis C virus RNA-dependent RNA polymerase.
AB  - A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA
      polymerase (RdRp), [(1R)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4
      b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput
      screening followed by chemical optimization. HCV-371 displayed broad inhibitory
      activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations
      ranging from 0.3 to 1.8 microM for 90% of the isolates derived from HCV genotypes
      1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human
      polymerases, including mitochondrial DNA polymerase gamma, and other unrelated
      viral polymerases, demonstrating its specificity for the HCV polymerase. A single
      administration of HCV-371 to cells containing the HCV subgenomic replicon for 3
      days resulted in a dose-dependent reduction of the steady-state levels of viral
      RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log10
      reduction in the HCV RNA level. In comparison, multiple treatments with a similar
      inhibitory dose of alpha interferon resulted in a 2-log10 reduction of the viral
      RNA level. In addition, treatment of cells with a combination of HCV-371 and
      pegylated alpha interferon resulted in an additive antiviral activity. Within the
      effective antiviral concentrations of HCV-371, there was no effect on cell
      viability and metabolism. The intracellular antiviral specificity of HCV-371 was
      demonstrated by its lack of activity in cells infected with several DNA or RNA
      viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an
      apparent dissociation constant of 150 nM, leading to high selectivity and lack of
      cytotoxicity in the antiviral assays.

PMID- 15561862
TI  - Evaluation of antibiotic susceptibilities of Ehrlichia canis, Ehrlichia
      chaffeensis, and Anaplasma phagocytophilum by real-time PCR.
AB  - We determined MICs of antibiotics against Anaplasma phagocytophilum, Ehrlichia
      chaffeensis, and Ehrlichia canis by real-time quantitative PCR. The doubling
      times of the organisms were established: 19 h for E. chaffeensis, 26 h for A.
      phagocytophilum, and 28 h for E. canis. In comparison to the reference method for
      determining sensitivities, which uses Diff-Quick staining, our PCR assay was very
      sensitive and specific. We confirmed that doxycycline and rifampin are highly
      active against these bacteria and found variable susceptibilities to
      fluoroquinolones; A. phagocytophilum was susceptible, but E. canis and E.
      chaffeensis were only partly susceptible. Beta-lactam compounds, cotrimoxazole,
      macrolide compounds, and telithromycin showed no activity against any of the
      three organisms. Thiamphenicol was found to be more active than chloramphenicol.
      For the first time, we showed that these three species have numerous point
      mutations in their 23S RNA genes, with those at positions 754, 2057, 2058, 2059,
      and 2611 (Escherichia coli numbering) known to confer resistance to macrolide
      compounds in other bacteria. The role of each of these mutations in resistance to
      these drugs should be investigated in the future. Our study confirms previous
      reports that quantitative PCR is a reliable method for determining antibiotic
      susceptibility; therefore, it might be useful for screening new drugs.

PMID- 15561863
TI  - Molecular and kinetic comparison of the novel extended-spectrum beta-lactamases
      CTX-M-25 and CTX-M-26.
AB  - CTX-M-25 is a novel extended-spectrum beta-lactamase isolated from a single
      Canadian Escherichia coli isolate. Susceptibility testing demonstrated that this
      enzyme confers resistance to both cefotaxime and ceftazidime, but the level of
      resistance was reduced with the addition of beta-lactamase inhibitors. The
      bla(CTX-M-25) gene was detected on a 111-kb plasmid. It is a member of the CTX-M
      8 group and has the closest amino acid identity (99%; three amino acid
      substitutions) with CTX-M-26. The bla(CTX-M-26) gene was detected on a 100-kb
      plasmid isolated from a Klebsiella pneumoniae strain from the United Kingdom, and
      plasmid profiling revealed that it showed some homology to the bla(CTX-M-25)
      harboring plasmid. Both CTX-M genes were located downstream of ISEcp1, although
      the copy upstream of bla(CTX-M-25) was disrupted by IS50-A. Comparative kinetic
      studies of recombinant CTX-M-25 and CTX-M-26 enzymes showed that CTX-M-25 has a
      higher level of ceftazidime hydrolysis (kcat values, 33 and 0.005 s(-1) for CTX-M
      25 and CTX-M-26, respectively).

PMID- 15561864
TI  - Pharmacokinetics in animals and humans of a first-in-class peptide deformylase
      inhibitor.
AB  - BB-83698, a potent and selective inhibitor of peptide deformylase, was the first
      compound of this novel antibacterial class to progress to clinical trials. Single
      and/or multiple-dose studies with doses ranging from 10 to 50 mg of BB-83698/kg
      of body weight were done with mice, rats, and dogs. Intravenous pharmacokinetics
      were characterized by low to moderate clearances and moderate volumes of
      distribution for all species. In dogs, but not in rodents, central nervous system
      (CNS) effects were dose limiting for intravenously administered BB-83698 and were
      suspected to be related to a high maximum concentration of the agent in plasma
      (Cmax) rather than to total systemic exposure. Controlled infusion studies with
      dogs demonstrated that CNS effects could be avoided without compromising systemic
      exposure by reducing the Cmax. A randomized, double-blind, placebo-controlled,
      five-way-crossover, single-dose-escalation, phase I study to explore the safety,
      tolerability, and pharmacokinetics of intravenous BB-83698 at doses ranging from
      10 to 475 mg was performed with healthy male volunteers. Systemic exposures were
      generally in linear relationships with administered doses in animals and humans.
      Pharmacokinetics were consistent, predictable, and exhibited good allometric
      scaling among all species (r2 >0.98). Moreover, BB-83698 dosing in humans
      proceeded to a predicted efficacious exposure (the area under the concentration
      time curve/MIC ratio, up to 184) without any clinically significant adverse
      effects.

PMID- 15561865
TI  - Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year
      period in patients from Seoul, South Korea.
AB  - Recently, the development of antibiotic resistance emerged as a significant
      clinical problem in the eradication of Helicobacter pylori. We investigated the
      MICs of antibiotics for 135 H. pylori isolates from adults in Seoul, South Korea,
      over the past 16 years. The MICs of amoxicillin, clarithromycin, metronidazole,
      tetracycline, azithromycin, and ciprofloxacin increased from 1987 to 2003. Rates
      of primary resistance to clarithromycin increased from 2.8% in 1994 to 13.8% in
      2003. The A2144G mutation was frequently observed in the 23S rRNA gene in
      clarithromycin-resistant isolates. The increase in resistance to clarithromycin
      seems to result in a decrease in eradication efficacy for H. pylori. These
      results suggest that the MICs of several antibiotics for H. pylori have increased
      over the past 16 years in Seoul.

PMID- 15561866
TI  - Atovaquone maintenance therapy prevents reactivation of toxoplasmic encephalitis
      in a murine model of reactivated toxoplasmosis.
AB  - Acute therapy with pyrimethamine plus sulfadiazine is the treatment of choice for
      reactivated toxoplasmic encephalitis (TE). Acute therapy is followed by lifelong
      maintenance therapy (secondary prophylaxis) with the same drugs at lower dosages.
      The use of pyrimethamine plus sulfadiazine is hampered by severe side effects
      including allergic reactions and hematotoxicity. Alternative treatment regimens
      with pyrimethamine plus clindamycin or other antiparasitic drugs are less
      efficacious. Atovaquone nanosuspensions show excellent therapeutic effects for
      "acute" intravenous (i.v.) treatment of reactivated TE in a murine model. In the
      present study, the therapeutic efficacy of atovaquone for oral "maintenance"
      therapy was investigated. Mice with a targeted mutation in the interferon
      regulatory factor 8 gene were latently infected with Toxoplasma gondii, developed
      reactivated TE, and received acute i.v. therapy with atovaquone nanosuspensions.
      Mice were then treated orally with atovaquone suspension or other antiparasitic
      drugs to prevent relapse of TE. Maintenance therapy with atovaquone at daily
      doses of 50 or 100 mg/kg (body weight) protected mice against reactivated TE and
      death. This maintenance treatment was superior to standard therapy with
      pyrimethamine plus sulfadiazine. The latter combination was superior to the
      combination of pyrimethamine plus clindamycin. Inflammatory changes in the brain
      parenchyma and meninges, as well as parasite numbers, in the brains of mice
      confirmed the therapeutic efficacy of atovaquone for maintenance therapy.
      Atovaquone was detectable in sera, brains, livers, and lungs of infected mice by
      high-performance liquid chromatography and/or mass spectrometry. In conclusion,
      atovaquone appears to be superior to the standard maintenance therapy regimens in
      a murine model of reactivated TE. The therapeutic efficacy of atovaquone for
      maintenance therapy against TE should be further investigated in clinical trials.

PMID- 15561867
TI  - Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic
      anti-influenza virus effects in MDCK cells.
AB  - There is insufficient information about combination therapy with approved anti
      influenza agents. We tested combinations that paired a neuraminidase (NA)
      inhibitor (zanamivir, oseltamivir carboxylate, or peramivir) with rimantadine
      against infection of MDCK cells with H1N1 and H3N2 subtypes of influenza A virus
      and characterized their mode of interaction. When reduction of extracellular
      virus was analyzed by individual regression models and three-dimensional
      representations of the data, all three combinations showed additive and
      synergistic effects with no cytotoxicity. Maximum synergy against A/New
      Caledonia/20/99 (H1N1) virus infection was observed with <2.5 microM rimantadine
      paired with low concentrations of NA inhibitors. All combinations reduced the
      extracellular yield of A/Panama/2007/99 (H3N2) influenza virus synergistically.
      However, our findings were different for the cell-associated virus yield. At some
      drug concentrations, the yield of cell-associated virus was inhibited
      antagonistically. Therefore, the method of analysis can be a crucial factor in
      evaluating the interactions of drugs with different mechanisms. We hypothesize
      that assays based on cell-associated virus yield may underestimate the efficacies
      of drug combinations that include an NA inhibitor. Taken together, our results
      suggest that regimens that combine NA inhibitors and rimantadine exert
      synergistic anti-influenza effects in vitro. These findings provide baseline
      information for therapeutic testing of the drug combinations in vivo.

PMID- 15561868
TI  - Association of a novel human immunodeficiency virus type 1 protease substrate
      cleft mutation, L23I, with protease inhibitor therapy and in vitro drug
      resistance.
AB  - We observed a previously uncharacterized mutation in the protease substrate
      cleft, L23I, in 31 of 4,303 persons undergoing human immunodeficiency virus type
      1 genotypic resistance testing. In combination with V82I, L23I was associated
      with a sevenfold reduction in nelfinavir susceptibility and a decrease in
      replication capacity. In combination with other drug resistance mutations, L23I
      was associated with multidrug resistance and a compensatory increase in
      replication capacity.

PMID- 15561869
TI  - Polymorphism in plasmodium falciparum drug transporter proteins and reversal of
      in vitro chloroquine resistance by a 9,10-dihydroethanoanthracene derivative.
AB  - BG958 reverses resistance in chloroquine-resistant isolates from different
      countries. Five mutations in the Plasmodium falciparum crt (pfcrt) gene resulting
      in the amino acid changes K76T, M74I, N75E, A220S, and R371I are systematically
      identified in resistance-reversed Asian, African, and Brazilian parasites which
      possess the pfcrt (CIET) haplotype. In combination with BG958, the activity of
      chloroquine is increased in parasites with the N86Y mutation in pfmdr1.

PMID- 15561870
TI  - Beta-lactamase gene expression in a penicillin-resistant Bacillus anthracis
      strain.
AB  - Expression of the bla1 and bla2 genes in an archetypal Bacillus anthracis strain
      is insufficient for penicillin resistance. In a penicillin-resistant clinical
      isolate, both genes are highly transcribed, but bla1 is the major contributor to
      high-level resistance to ampicillin. Differential expression of the bla genes is
      dependent upon strain background.

PMID- 15561871
TI  - Glucocorticoids increase in vitro and in vivo activities of antibiotics against
      Chlamydophila pneumoniae.
AB  - The in vitro and in vivo antichlamydial activities of dexamethasone and
      beclomethasone alone and in combination with an antibiotic were tested. In vitro,
      dexamethasone and beclomethasone decreased the number of inclusion-forming units
      versus the control number (P < 0.001). The combination of glucocorticoids with
      azithromycin, telithromycin, or levofloxacin was more active than antibiotics
      used alone (P < 0.001). The combination, tested in a murine Chlamydophila
      pneumoniae infection model, produced similar results.

PMID- 15561872
TI  - VanE-type vancomycin-resistant Enterococcus faecalis clinical isolates from
      Australia.
AB  - Three distinct Enterococcus faecalis VanE-type isolates-BM4574, BM4575, and
      BM4576-obtained in Australia were studied. Expression of the resistance genes was
      constitutive in BM4575, probably due to a 2-bp deletion into the vanSE gene, and
      inducible in BM4574 and BM4576. Transcription analysis of the vanE operons
      suggested that the five genes were cotranscribed from an initiation site located
      25 bp upstream from the ATG start codon of vanE.

PMID- 15561873
TI  - PCR-restriction fragment length polymorphism assay for detection of gyrA
      mutations associated with fluoroquinolone resistance in Campylobacter coli.
AB  - A fragment of the gyrA gene was sequenced from 34 isolates of Campylobacter coli,
      including 23 isolates resistant to ciprofloxacin. All ciprofloxacin-resistant
      isolates examined by DNA sequencing carried a point mutation at position Thr-86
      on the gyrA gene product, involving the replacement of Thr-86 by Ile. A combined
      PCR-restriction fragment length polymorphism technique using RsaI was developed
      to detect this mutation.

PMID- 15561874
TI  - Effects of a number of classes of 50S inhibitors on stop codon readthrough during
      protein synthesis.
AB  - The effect of a number of antibiotics on stop codon readthrough during protein
      synthesis in Escherichia coli was examined. Inhibitors which bind close to the
      entrance of the peptide exit tunnel on the 50S ribosomal subunit promote
      substantial levels of readthrough, presumably by disrupting the mechanism of
      peptide release.

PMID- 15561875
TI  - Antimycoplasmal activity of hydroxytyrosol.
AB  - The aim of this study was to investigate the in vitro antimycoplasmal activity of
      hydroxytyrosol. Twenty strains of Mycoplasma hominis, three strains of Mycoplasma
      fermentans, and one strain of Mycoplasma pneumoniae were used. For M. pneumoniae,
      M. hominis, and M. fermentans, the MICs were 0.5, 0.03 (for 90% of the strains
      tested), and 0.25 microg/ml, respectively.

PMID- 15561876
TI  - Chromosome-encoded CTX-M-3 from Kluyvera ascorbata: a possible origin of plasmid
      borne CTX-M-1-derived cefotaximases.
AB  - A gene identical to plasmid-borne bla(CTX-M-3) is present in the chromosome of
      one Kluyvera ascorbata strain. It is associated with a structure including an
      inverted repeat right and an open reading frame 477-like gene probably involved
      in the mobilization of bla(CTX-M-3). Two other K. ascorbata strains rendered the
      previously described bla(KLUA-9) gene.

PMID- 15561877
TI  - In vitro activities of OPT-80 and comparator drugs against intestinal bacteria.
AB  - The activities of OPT-80 against 453 intestinal bacteria were compared with those
      of seven other drugs. OPT-80 showed good activity against most clostridia,
      staphylococci, and enterococci, but streptococci, aerobic and facultative gram
      negative rods, anaerobic gram-negative rods, and Clostridium ramosum were
      resistant. Poor activity against anaerobic gram-negative rods may maintain
      colonization resistance.

PMID- 15561878
TI  - Antimicrobial susceptibility of Bordetella bronchiseptica isolates from porcine
      respiratory tract infections.
AB  - MICs for 349 Bordetella bronchiseptica isolates from respiratory tract infections
      of swine were determined by broth microdilution. The lowest MIC at which 90% of
      isolates tested are inhibited (MIC90) was that of tetracycline and enrofloxacin
      (0.5 microg/ml), whereas the highest MIC90s were those of tilmicosin and
      cephalothin (32 microg/ml) as well as streptomycin (256 microg/ml).

PMID- 15561879
TI  - A subinhibitory concentration of clarithromycin inhibits Mycobacterium avium
      biofilm formation.
AB  - Mycobacterium avium causes disseminated infection in immunosuppressed individuals
      and lung infection in patients with chronic lung diseases. M. avium forms biofilm
      in the environment and possibly in human airways. Antibiotics with activity
      against the bacterium could inhibit biofilm formation. Clarithromycin inhibits
      biofilm formation but has no activity against established biofilm.

PMID- 15561880
TI  - Need for early antifungal treatment confirmed in experimental disseminated
      Candida albicans infection.
AB  - Groups of mice infected intravenously with Candida albicans were treated
      intraperitoneally with amphotericin B, caspofungin, or fluconazole, starting at
      intervals before and after challenge. Survival was longest and tissue burdens
      were most reduced with early treatment, and survival times fell proportionately
      as treatment was delayed, reinforcing clinical recommendations for the earliest
      possible initiation of antifungal therapy.

PMID- 15561881
TI  - Members of the genera Paenibacillus and Rhodococcus harbor genes homologous to
      enterococcal glycopeptide resistance genes vanA and vanB.
AB  - Genes homologous to enterococcal glycopeptide resistance genes vanA and vanB were
      found in glycopeptide-resistant Paenibacillus and Rhodococcus strains from soil.
      The putative D-Ala:D-Lac ligase genes in Paenibacillus thiaminolyticus PT-2B1 and
      Paenibacillus apiarius PA-B2B were closely related to vanA (92 and 87%) and
      flanked by genes homologous to vanH and vanX in vanA operons.

PMID- 15561882
TI  - The synthetic N-terminal peptide of human lactoferrin, hLF(1-11), is highly
      effective against experimental infection caused by multidrug-resistant
      Acinetobacter baumannii.
AB  - The lactoferrin-derived peptide hLF(1-11), but not its control peptide, was
      highly effective against five multidrug-resistant Acinetobacter baumannii strains
      in vitro (3 to 4 log reduction) and against four of these strains in an
      experimental infection in mice (2 to 3 log reduction). Therefore, this peptide is
      a promising candidate as a novel agent against infections with multidrug
      resistant A. baumannii.

PMID- 15561883
TI  - In vitro interactions between antifungals and immunosuppressants against
      Aspergillus fumigatus isolates from transplant and nontransplant patients.
AB  - We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus
      clinical isolates (6 transplant recipients and 6 nontransplant patients) with
      three antifungal agents (amphotericin B, voriconazole, and caspofungin) and three
      immunosuppressants (FK506, cyclosporine, and rapamycin). We were not able to
      detect a difference in calcineurin inhibitor antifungal activity against isolates
      from transplant recipients and nontransplant patients.

PMID- 15561884
TI  - Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility
      to vancomycin.
AB  - To investigate the prevalence of Staphylococcus aureus with reduced
      susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains
      in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12
      Asian countries were screened by using brain heart infusion agar plates
      containing 4 mg of vancomycin per liter. The presence of strains that were
      heterointermediately resistant to vancomycin (hVISA) was confirmed by population
      analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58
      isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea,
      Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither
      vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates
      were found among MRSA isolates from Asian countries in this survey.

PMID- 15561885
TI  - First detection of a carbapenem-hydrolyzing metalloenzyme in an
      Enterobacteriaceae isolate in France.

PMID- 15561887
TI  - Roles of vascular endothelial growth factor receptor 3 signaling in
      differentiation of mouse embryonic stem cell-derived vascular progenitor cells
      into endothelial cells.
AB  - Vascular endothelial growth factor receptor 2 (VEGFR2/Flk-1)-positive cells
      derived from embryonic stem (ES) cells serve as vascular progenitors, which
      differentiate into endothelial cells (ECs) in the presence of VEGF-A. VEGFR3/Flt
      4 (fms-like tyrosine kinase 4) signaling is known to be important for the
      development of lymphatic endothelial cells (LECs). To elucidate the roles of
      VEGFR3 signaling in the differentiation of vascular progenitor cells into ECs, we
      introduced various types of VEGFR3 cDNAs into mouse ES cells. VEGF-C, a ligand
      for VEGFR2 and VEGFR3, stimulated the endothelial differentiation of the VEGFR2+
      cells transfected with the VEGFR3 cDNA but not those transfected with kinase
      negative mutants of VEGFR3. The VEGFR3-transfected ECs exhibited high expression
      levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), one of the
      markers of LECs, and showed efficient binding of hyaluronan. VEGF-C(C152S), which
      is able to activate VEGFR3 but not VEGFR2, failed to induce the endothelial
      differentiation of mock- and VEGFR3-transfected VEGFR2(+) cells, suggesting the
      essential role of VEGFR2 signaling for endothelial differentiation. Furthermore,
      kinase-negative mutants of VEGFR3 prevented the VEGF-C-mediated endothelial
      differentiation of the vascular progenitor cells. Thus, VEGFR2 signaling is
      required for the endothelial differentiation of mouse ES cells induced by VEGF-C,
      and VEGFR3 signaling may confer lymphatic endothelial-like phenotypes to ECs.

PMID- 15561888
TI  - Different isoforms of BSAP regulate expression of AID in normal and chronic
      lymphocytic leukemia B cells.
AB  - Activation-induced cytidine deaminase (AID) is key to initiating somatic
      hypermutation (SHM) and class switch recombination (CSR), but its mode of action
      and regulation remains unclear. Since Pax-5 and Id-2 transcription factors play
      an opposing role in AID regulation, we have studied the expression of Pax-5, Id
      2, and prdm-1 genes in 54 chronic lymphocytic leukemia (CLL) B cells. In 21
      cases, presence of AID is constantly associated with high expression of the
      complete form of the Pax-5 gene (Pax-5a) and lower expression of the Id-2 and
      prdm-1 transcripts. In 33 cases, the absence of AID expression and CSR is
      associated with a reduction of Pax-5a and the appearance of a spliced form with a
      deletion in exon 8 (Pax-5/Delta-Ex8). Stimulation with CD40L+interleukin 4 (IL-4)
      induces CSR, the presence of AID transcripts, up-regulation of Pax-5a and down
      regulation of Pax-5/Delta-Ex8, and Id-2 and prdm-1 transcripts. Pax-5a and Pax
      5/Delta-Ex8 are translated into 2 isoforms of the B-cell-specific activator
      protein (BSAP) and both are able to bind the AID-promoter region. Overall, these
      results suggest that Pax-5/Delta-Ex8 could play an important role in the control
      of its own transcription and indirectly in AID expression and CSR.

PMID- 15561889
TI  - A novel NF-kappaB inhibitor, IMD-0354, suppresses neoplastic proliferation of
      human mast cells with constitutively activated c-kit receptors.
AB  - Constitutive phosphorylation of c-kit tyrosine kinase is the major cause of
      factor-independent proliferation of mast cells. Recently available tyrosine
      kinase inhibitors have shown marked activity against mast cell lines that carry
      wild-type c-kit, and some, but not others, carry mutant c-kit. Here we clearly
      demonstrated that a novel NF-kappaB inhibitor, IMD-0354, restrained factor
      independent proliferation of mast cells with c-kit mutations but not of normal
      mast cells. In HMC-1 cells with the Asp816Val and Val560Gly mutations, we found
      that NF-kappaB was constitutively activated without exogenous stimulation. When
      the DNA-binding activity of NF-kappaB was inhibited by treatment with IMD-0354,
      cell proliferation was completely suppressed. We detected the expression of
      cyclin D2, D3, and E in HMC-1 cells and observed that cyclin D3 expression was
      dramatically decreased by treatment with IMD-0354. Abolishing protein kinase C or
      phosphatidylinositol 3 kinase pathways also inhibited NF-kappaB translocation to
      the nucleus, indicating the involvement of these signaling cascades in NF-kappaB
      activation in HMC-1 cells. Our findings indicated that autophosphorylated c-kit
      receptors induced NF-kappaB activation, resulting in the up-regulation of cyclin
      D3 expression and cell cycle progression. The observations from the current study
      suggest a therapeutic potential, in systemic mastocytosis, for compounds that
      interfere with NF-kappaB signaling.

PMID- 15561890
TI  - Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of
      patients with multiple myeloma.
AB  - Multiple myeloma (MM) is one of the most common hematologic malignancies. Despite
      extensive therapeutical approaches, cures remain rare exceptions. An important
      issue for future immunologic treatments is the characterization of appropriate
      tumor-associated antigens. Recently, a highly glycosylated mucin MUC1 was
      detected on a majority of multiple myeloma cell lines. We analyzed bone marrow
      and peripheral blood of 68 patients with HLA-A2-positive myeloma for the presence
      and functional activity of CD8 T cells specific for the MUC1-derived peptide
      LLLLTVLTV. Forty-four percent of the patients with MM contained elevated
      frequencies of MUC1-specific CD8 T cells in freshly isolated samples from
      peripheral blood (PB) or bone marrow (BM) compared with corresponding samples
      from healthy donors. BM-residing T cells possessed a higher functional capacity
      upon specific reactivation than PB-derived T cells with regard to interferon
      gamma (IFN-gamma) secretion, perforin production, and cytotoxicity.

PMID- 15561893
TI  - Brain. Editorial.

PMID- 15561891
TI  - Skin denervation in type 2 diabetes: correlations with diabetic duration and
      functional impairments--a comment.

PMID- 15561895
TI  - Inhibiting leukocyte recruitment to the brain by IVIg: is it relevant to the
      treatment of demyelinating CNS disorders?

PMID- 15561896
TI  - Impact of treatment on islet function in type 2 diabetes.

PMID- 15561897
TI  - Toward linking structure with function in ATP-sensitive K+ channels.
AB  - Advances in understanding the overall structural features of inward rectifiers
      and ATP-binding cassette (ABC) transporters are providing novel insight into the
      architecture of ATP-sensitive K+ channels (KATP channels) (KIR6.0/SUR)4. The
      structure of the K(IR) pore has been modeled on bacterial K+ channels, while the
      lipid-A exporter, MsbA, provides a template for the MDR-like core of sulfonylurea
      receptor (SUR)-1. TMD0, an NH2-terminal bundle of five alpha-helices found in
      SURs, binds to and activates KIR6.0. The adjacent cytoplasmic L0 linker serves a
      dual function, acting as a tether to link the MDR-like core to the KIR6.2/TMD0
      complex and exerting bidirectional control over channel gating via interactions
      with the NH2-terminus of the KIR. Homology modeling of the SUR1 core offers the
      possibility of defining the glibenclamide/sulfonylurea binding pocket. Consistent
      with 30-year-old studies on the pharmacology of hypoglycemic agents, the pocket
      is bipartite. Elements of the COOH-terminal half of the core recognize a
      hydrophobic group in glibenclamide, adjacent to the sulfonylurea moiety, to
      provide selectivity for SUR1, while the benzamido group appears to be in
      proximity to L0 and the KIR NH2-terminus.

PMID- 15561898
TI  - Metabolic regulation of the pancreatic beta-cell ATP-sensitive K+ channel: a pas
      de deux.
AB  - Closure of ATP-sensitive K+ channels (KATP channels) is a key step in glucose
      stimulated insulin secretion. The precise mechanism(s) by which glucose
      metabolism regulates KATP channel activity, however, remains controversial. It is
      widely believed that the principal determinants are the intracellular
      concentrations of the metabolic ligands, ATP and ADP, which have opposing actions
      on KATP channels, with ATP closing and MgADP opening the channel. However, the
      sensitivity of the channel to these nucleotides in the intact cell, and their
      relative contribution to the regulation of channel activity, remains unclear. The
      precise role of phosphoinositides and long-chain acyl-CoA esters, which are
      capable of modulating the channel ATP sensitivity, is also uncertain.
      Furthermore, it is still a matter of debate whether it is changes in the
      concentration of ATP, of MgADP, or of other agents, which couples glucose
      metabolism to KATP channel activity. In this article, we review current knowledge
      of the metabolic regulation of the KATP channel and provide evidence that MgADP
      (or MgATP hydrolysis), acting at the regulatory subunit of the channel, shifts
      the ATP concentration-response curve into a range in which the channel pore can
      respond to dynamic changes in cytosolic ATP. This metabolic pas de deux
      orchestrates the pivotal role of ATP in metabolic regulation of the KATP channel.

PMID- 15561899
TI  - Identification of a functionally important negatively charged residue within the
      second catalytic site of the SUR1 nucleotide-binding domains.
AB  - The ATP-sensitive K+ channel (KATP channel) couples glucose metabolism to insulin
      secretion in pancreatic beta-cells. It is comprised of sulfonylurea receptor
      (SUR)-1 and Kir6.2 proteins. Binding of Mg nucleotides to the nucleotide-binding
      domains (NBDs) of SUR1 stimulates channel opening and leads to membrane
      hyperpolarization and inhibition of insulin secretion. To elucidate the
      structural basis of this regulation, we constructed a molecular model of the NBDs
      of SUR1, based on the crystal structures of mammalian proteins that belong to the
      same family of ATP-binding cassette transporter proteins. This model is a dimer
      in which there are two nucleotide-binding sites, each of which contains residues
      from NBD1 as well as from NBD2. It makes the novel prediction that residue D860
      in NBD1 helps coordinate Mg nucleotides at site 2. We tested this prediction
      experimentally and found that, unlike wild-type channels, channels containing the
      SUR1-D860A mutation were not activated by MgADP in either the presence or absence
      of MgATP. Our model should be useful for designing experiments aimed at
      elucidating the relationship between the structure and function of the KATP
      channel.

PMID- 15561900
TI  - Effect of two amino acids in TM17 of Sulfonylurea receptor SUR1 on the binding of
      ATP-sensitive K+ channel modulators.
AB  - The sulfonylurea receptor (SUR) is the important regulatory subunit of ATP
      sensitive K+ channels. It is an ATP-binding cassette protein comprising 17
      transmembrane helices. SUR is endowed with binding sites for channel blockers
      like the antidiabetic sulfonylurea glibenclamide and for the chemically very
      heterogeneous channel openers. SUR1, the typical pancreatic SUR isoform, shows
      much higher affinity for glibenclamide but considerably lower affinity for most
      openers than SUR2. In radioligand binding assays, we investigated the role of two
      amino acids, T1285 and M1289, located in transmembrane helix (TM)-17, in opener
      binding to SUR1. These amino acids were exchanged for the corresponding amino
      acids of SUR2. In competition experiments using [3H]glibenclamide as radioligand,
      SUR1(T1285L, M1289T) showed much higher affinity toward the cyanoguanidine
      openers pinacidil and P1075 than SUR1 wild type. The affinity for the
      thioformamide aprikalim was also markedly increased. In contrast, the affinity
      for the benzopyrans rilmakalim and levcromakalim was unaffected; however, the
      amount of displaced [3H]glibenclamide binding was nearly doubled. The binding
      properties of the opener diazoxide and the blocker glibenclamide were unchanged.
      In conclusion, mutation of two amino acids in TM17 of SUR1, especially of M1289,
      leads to class-specific effects on opener binding by increasing opener affinity
      or by changing allosteric coupling between opener and glibenclamide binding.

PMID- 15561901
TI  - Glucose dependence of imidazoline-induced insulin secretion: different
      characteristics of two ATP-Sensitive K+ channel-blocking compounds.
AB  - The glucose dependence of the insulinotropic action of KATP channel-blocking
      imidazoline compounds was investigated. Administration of 100 micromol/l
      phentolamine, but not 100 micromol/l efaroxan, markedly increased insulin
      secretion of freshly isolated mouse islets when the perifusion medium contained 5
      mmol/l glucose. When the glucose concentration was raised to 10 mmol/l in the
      continued presence of either imidazoline, a clear potentiation of secretion
      occurred as compared with 10 mmol/l glucose alone. In the presence of efaroxan, a
      brisk first-phase-like increase was followed by a sustained phase, whereas a more
      gradual increase resulted in the presence of phentolamine. Administration of 100
      micromol/l phentolamine was somewhat more effective than 100 micromol/l efaroxan
      to inhibit KATP channel activity in intact cultured beta-cells (reduction by 96
      vs. 83%). Both compounds were similarly effective to depolarize the beta-cells.
      When measured by the perforated patch-technique, the depolarization by efaroxan
      was often oscillatory, whereas that by phentolamine was sustained. In perifused
      cultured islets, both compounds increased the cytosolic calcium concentration
      ([Ca2+]c) in the presence of 5 and 10 mmol/l glucose. Efaroxan induced large
      amplitude oscillations of [Ca2+]c, whereas phentolamine induced a sustained
      increase. It appears that a KATP channel block by imidazolines is not
      incompatible with a glucose-selective enhancement of insulin secretion. The
      glucose selectivity of efaroxan may involve an inhibitory effect distal to
      [Ca2+]c increase and/or the generation of [Ca2+]c oscillations.

PMID- 15561902
TI  - Desensitization of insulin secretion by depolarizing insulin secretagogues.
AB  - Prolonged stimulation of insulin secretion by depolarization and Ca2+ influx
      regularly leads to a reversible state of decreased secretory responsiveness to
      nutrient and nonnutrient stimuli. This state is termed "desensitization." The
      onset of desensitization may occur within 1 h of exposure to depolarizing
      stimuli. Desensitization by exposure to sulfonylureas, imidazolines, or quinine
      produces a marked cross-desensitization against other ATP-sensitive K+ channel
      (KATP channel)-blocking secretagogues. However, desensitized beta-cells do not
      necessarily show changes in KATP channel activity or Ca2+ handling. Care has to
      be taken to distinguish desensitization-induced changes in signaling from effects
      due to the persisting presence of secretagogues. The desensitization by
      depolarizing secretagogues is mostly accompanied by a reduced content of
      immunoreactive insulin and a marked reduction of secretory granules in the beta
      cells. In vitro recovery from a desensitization by the imidazoline efaroxan was
      nearly complete after 4 h. At this time point the depletion of the granule
      content was partially reversed. Apparently, recovery from desensitization affects
      the whole lifespan of a granule from biogenesis to exocytosis. There is, however,
      no direct relation between the beta-cell granule content and the secretory
      responsiveness. Even though a prolonged exposure of isolated islets to
      depolarizing secretagogues is often associated with the occurrence of
      ultrastructural damage to beta-cells, we could not find a cogent link between
      depolarization and Ca2+ influx and apoptotic or necrotic beta-cell death.

PMID- 15561903
TI  - Kinetics-effect relations of insulin-releasing drugs in patients with type 2
      diabetes: brief overview.
AB  - Sulfonylureas and glinides have similar mechanisms of action but differ in
      receptor affinity and binding sites and in absorption and elimination rates. This
      promotes differences in potency, rate of onset, and duration of action. While
      prominent in single-dose studies, these differences have less importance during
      long-term sulfonylurea treatment: at ordinary dosages, rapid- and short-acting
      (glipizide) and slow- and long-acting (glyburide) sulfonylureas maintained
      continuously effective plasma levels and similar 24-h glucose control. Moreover,
      there was no difference in patient outcome between the first-generation
      sulfonylurea chlorpropamide and the second-generation glyburide in the U.K.
      Prospective Diabetes Study. However, the risk of long-lasting and hence dangerous
      hypoglycemia is higher with these two long-acting sulfonylureas. Conversely, this
      risk should be low with the short-acting glinides, but seemingly at the expense
      of less effective glucose control. The most important kinetics-effect relations
      are that hyperglycemia delays sulfonylurea absorption and that the sulfonylurea
      dose-response curve is bell shaped; continuous sulfonylurea exposure over a
      certain level (e.g., 10 mg glipizide) impairs rather than improves insulin and
      glucose responses to sulfonylurea (downregulation). Accordingly, a vicious circle
      may be established: unrelenting hyperglycemia may promote sulfonylurea dose
      increase, which increases hyperglycemia, promoting further dose increase and
      eventually therapeutic failure.

PMID- 15561904
TI  - The impact of ATP-sensitive K+ channel subtype selectivity of insulin
      secretagogues for the coronary vasculature and the myocardium.
AB  - Insulin secretagogues (sulfonylureas and glinides) increase insulin secretion by
      closing the ATP-sensitive K+ channel (KATP channel) in the pancreatic beta-cell
      membrane. KATP channels subserve important functions also in the heart. First,
      KATP channels in coronary myocytes contribute to the control of coronary blood
      flow at rest and in hypoxia. Second, KATP channels in the sarcolemma of
      cardiomyocytes (sarcKATP channels) are required for adaptation of the heart to
      stress. In addition, the opening of sarcKATP channels and of KATP channels in the
      inner membrane of mitochondria (mitoKATP channels) plays a central role in
      ischemic preconditioning. Opening of sarcKATP channels also underlies the ST
      segment elevation of the electrocardiogram, the primary diagnostic tool for
      initiation of lysis therapy in acute myocardial infarction. Therefore, inhibition
      of cardiovascular KATP channels by insulin secretagogues is considered to
      increase cardiovascular risk. Electrophysiological experiments have shown that
      the secretagogues differ in their selectivity for the pancreatic over the
      cardiovascular KATP channels, being either highly selective (approximately
      1,000x; short sulfonylureas such as nateglinide and mitiglinide), moderately
      selective (10-20x; long sulfonylureas such as glibenclamide [glyburide]), or
      essentially nonselective (<2x; repaglinide). New binding studies presented here
      give broadly similar results. In clinical studies, these differences are not yet
      taken into account. The hypothesis that the in vitro selectivity of the insulin
      secretagogues is of importance for the cardiovascular outcome of diabetic
      patients with coronary artery disease needs to be tested.

PMID- 15561905
TI  - Five stages of evolving beta-cell dysfunction during progression to diabetes.
AB  - This article proposes five stages in the progression of diabetes, each of which
      is characterized by different changes in beta-cell mass, phenotype, and function.
      Stage 1 is compensation: insulin secretion increases to maintain normoglycemia in
      the face of insulin resistance and/or decreasing beta-cell mass. This stage is
      characterized by maintenance of differentiated function with intact acute glucose
      stimulated insulin secretion (GSIS). Stage 2 occurs when glucose levels start to
      rise, reaching approximately 5.0-6.5 mmol/l; this is a stable state of beta-cell
      adaptation with loss of beta-cell mass and disruption of function as evidenced by
      diminished GSIS and beta-cell dedifferentiation. Stage 3 is a transient unstable
      period of early decompensation in which glucose levels rise relatively rapidly to
      the frank diabetes of stage 4, which is characterized as stable decompensation
      with more severe beta-cell dedifferentiation. Finally, stage 5 is characterized
      by severe decompensation representing a profound reduction in beta-cell mass with
      progression to ketosis. Movement across stages 1-4 can be in either direction.
      For example, individuals with treated type 2 diabetes can move from stage 4 to
      stage 1 or stage 2. For type 1 diabetes, as remission develops, progression from
      stage 4 to stage 2 is typically found. Delineation of these stages provides
      insight into the pathophysiology of both progression and remission of diabetes.

PMID- 15561906
TI  - Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+
      channel, predisposes to catecholamine-induced ventricular dysrhythmia.
AB  - Metabolic-sensing ATP-sensitive K+ channels (KATP channels) adjust membrane
      excitability to match cellular energetic demand. In the heart, KATP channel
      activity has been linked to homeostatic shortening of the action potential under
      stress, yet the requirement of channel function in securing cardiac electrical
      stability is only partially understood. Here, upon catecholamine challenge,
      disruption of KATP channels, by genetic deletion of the pore-forming Kir6.2
      subunit, produced defective cardiac action potential shortening, predisposing the
      myocardium to early afterdepolarizations. This deficit in repolarization reserve,
      demonstrated in Kir6.2-knockout hearts, translated into a high risk for induction
      of triggered activity and ventricular dysrhythmia. Thus, intact KATP channel
      function is mandatory for adequate repolarization under sympathetic stress
      providing electrical tolerance against triggered arrhythmia.

PMID- 15561907
TI  - ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise
      training, resulting in cardiac deficits.
AB  - Exercise training elicits a metabolic and cardiovascular response that underlies
      fitness. The molecular mechanisms that orchestrate this adaptive response and
      secure the wide-ranging gains of a regimented exercise program are poorly
      understood. Formed through association of the Kir6.2 pore and the sulfonylurea
      receptor, the stress-responsive ATP-sensitive K(+) channels (K(ATP) channels),
      with their metabolic-sensing capability and broad tissue expression, are
      potential candidates for integrating the systemic adaptive response to repetitive
      exercise. Here, the responses of mice lacking functional Kir6.2-containing K(ATP)
      channels (Kir6.2-KO) were compared with wild-type controls following a 28-day
      endurance swimming protocol. While chronic aquatic training resulted in lighter,
      leaner, and fitter wild-type animals, the Kir6.2-KO manifested less augmentation
      in exercise capacity and lacked metabolic improvement in body fat composition and
      glycemic handling with myocellular defects. Moreover, the repetitive stress of
      swimming unmasked a survival disadvantage in the Kir6.2-KO, associated with
      pathologic calcium-dependent structural damage in the heart and impaired cardiac
      performance. Thus, Kir6.2-containing K(ATP) channel activity is required for
      attainment of the physiologic benefits of exercise training without injury.

PMID- 15561908
TI  - Roles of ATP-sensitive K+ channels as metabolic sensors: studies of Kir6.x null
      mice.
AB  - ATP-sensitive K+ channels (KATP channels) are present in various tissues,
      including pancreatic beta-cells, heart, skeletal muscles, vascular smooth
      muscles, and brain. KATP channels are hetero-octameric proteins composed of
      inwardly rectifying K+ channel (Kir6.x) and sulfonylurea receptor (SUR) subunits.
      Different combinations of Kir6.x and SUR subunits comprise KATP channels with
      distinct electrophysiological and pharmacological properties. Recent studies of
      genetically engineered mice have provided insight into the physiological and
      pathophysiological roles of Kir6.x-containing KATP channels. Analysis of Kir6.2
      null mice has shown that Kir6.2/SUR1 channels in pancreatic beta-cells and the
      hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia
      induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are
      involved in glucose uptake in skeletal muscles. Kir6.2-containing KATP channels
      in brain also are involved in protection from hypoxia-induced generalized
      seizure. In cardiovascular tissues, Kir6.1-containing KATP channels are involved
      in regulation of vascular tonus. In addition, the Kir6.1 null mouse is a model of
      Prinzmetal angina in humans. Our studies of Kir6.2 null and Kir6.1 null mice
      reveal that KATP channels are critical metabolic sensors in acute metabolic
      changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.

PMID- 15561909
TI  - ATP-sensitive K+ channel-dependent regulation of glucagon release and electrical
      activity by glucose in wild-type and SUR1-/- mouse alpha-cells.
AB  - Patch-clamp recordings and glucagon release measurements were combined to
      determine the role of plasma membrane ATP-sensitive K+ channels (KATP channels)
      in the control of glucagon secretion from mouse pancreatic alpha-cells. In wild
      type mouse islets, glucose produced a concentration-dependent (half-maximal
      inhibitory concentration [IC50]=2.5 mmol/l) reduction of glucagon release.
      Maximum inhibition (approximately 50%) was attained at glucose concentrations >5
      mmol/l. The sulfonylureas tolbutamide (100 micromol/l) and glibenclamide (100
      nmol/l) inhibited glucagon secretion to the same extent as a maximally inhibitory
      concentration of glucose. In mice lacking functional KATP channels (SUR1-/-),
      glucagon secretion in the absence of glucose was lower than that observed in wild
      type islets and both glucose (0-20 mmol/l) and the sulfonylureas failed to
      inhibit glucagon secretion. Membrane potential recordings revealed that alpha
      cells generate action potentials in the absence of glucose. Addition of glucose
      depolarized the alpha-cell by approximately 7 mV and reduced spike height by 30%
      Application of tolbutamide likewise depolarized the alpha-cell (approximately 17
      mV) and reduced action potential amplitude (43%). Whereas insulin secretion
      increased monotonically with increasing external K+ concentrations (threshold 25
      mmol/l), glucagon secretion was paradoxically suppressed at intermediate
      concentrations (5.6-15 mmol/l), and stimulation was first detectable at >25
      mmol/l K+. In alpha-cells isolated from SUR1-/- mice, both tolbutamide and
      glucose failed to produce membrane depolarization. These effects correlated with
      the presence of a small (0.13 nS) sulfonylurea-sensitive conductance in wild-type
      but not in SUR1-/- alpha-cells. Recordings of the free cytoplasmic Ca2+
      concentration ([Ca2+]i) revealed that, whereas glucose lowered [Ca2+]i to the
      same extent as application of tolbutamide, the Na+ channel blocker tetrodotoxin,
      or the Ca2+ channel blocker Co2+ in wild-type alpha-cells, the sugar was far less
      effective on [Ca2+]i in SUR1-/- alpha-cells. We conclude that the KATP channel is
      involved in the control of glucagon secretion by regulating the membrane
      potential in the alpha-cell in a way reminiscent of that previously documented in
      insulin-releasing beta-cells. However, because alpha-cells possess a different
      complement of voltage-gated ion channels involved in action potential generation
      than the beta-cell, moderate membrane depolarization in alpha-cells is associated
      with reduced rather than increased electrical activity and secretion.

PMID- 15561910
TI  - Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of
      type 2 diabetes.
AB  - The incretin effect denominates the phenomenon that oral glucose elicits a higher
      insulin response than does intravenous glucose. The two hormones responsible for
      the incretin effect, glucose-dependent insulinotropic hormone (GIP) and glucagon
      like peptide-1 (GLP-1), are secreted after oral glucose loads and augment insulin
      secretion in response to hyperglycemia. In patients with type 2 diabetes, the
      incretin effect is reduced, and there is a moderate degree of GLP-1
      hyposecretion. However, the insulinotropic response to GLP-1 is well maintained
      in type 2 diabetes. GIP is secreted normally or hypersecreted in type 2 diabetes;
      however, the responsiveness of the endocrine pancreas to GIP is greatly reduced.
      In approximately 50% of first-degree relatives of patients with type 2 diabetes,
      similarly reduced insulinotropic responses toward exogenous GIP can be observed,
      without significantly changed secretion of GIP or GLP-1 after oral glucose. This
      opens the possibility that a reduced responsiveness to GIP is an early step in
      the pathogenesis of type 2 diabetes. On the other hand, this provides a basis to
      use incretin hormones, especially GLP-1 and its derivatives, to replace a
      deficiency in incretin-mediated insulin secretion in the treatment of type 2
      diabetes.

PMID- 15561911
TI  - The incretin approach for diabetes treatment: modulation of islet hormone release
      by GLP-1 agonism.
AB  - Glucagon-like peptide (GLP)-1 is a gut hormone that stimulates insulin secretion,
      gene expression, and beta-cell growth. Together with the related hormone glucose
      dependent insulinotropic polypeptide (GIP), it is responsible for the incretin
      effect, the augmentation of insulin secretion after oral as opposed to
      intravenous administration of glucose. Type 2 diabetic patients typically have
      little or no incretin-mediated augmentation of insulin secretion. This is due to
      decreased secretion of GLP-1 and loss of the insulinotropic effects of GIP. GLP
      1, however, retains insulinotropic effects, and the hormone effectively improves
      metabolism in patients with type 2 diabetes. Continuous subcutaneous
      administration greatly improved glucose profiles and lowered body weight and
      HbA1c levels. Further, free fatty acid levels were lowered, insulin resistance
      was improved, and beta-cell performance was greatly improved. The natural peptide
      is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV), but resistant
      analogs as well as inhibitors of DPP IV are now under development, and both
      approaches have shown remarkable efficacy in experimental and clinical studies.

PMID- 15561912
TI  - Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor
      desensitization in vitro but does not attenuate GLP-1R-dependent glucose
      homeostasis in vivo.
AB  - Glucagon-like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion
      and inhibits food intake, gastric emptying, and glucagon secretion, actions that
      promote reduction of fasting and postprandial glycemia in subjects with type 2
      diabetes. The rapid degradation of native GLP-1 has engendered interest in more
      stable longer-acting GLP-1 receptor agonists such as exendin-4 (Ex-4); however,
      the potential consequences of sustained GLP-1 receptor activation leading to
      receptor desensitization has not been extensively studied. We have now examined a
      range of GLP-1 receptor-dependent responses following treatment with Ex-4 using
      INS-1 cells in vitro and both wild-type control and MT-Ex-4 transgenic mice in
      vivo. Although both GLP-1 and Ex-4 acutely desensitized GLP-1 receptor-dependent
      cAMP accumulation in INS-1 cells, Ex-4 produced more sustained receptor
      desensitization, relative to GLP-1, in both acute (5-120 min) and chronic (24-72
      h) experiments. PMA (4-phorbol 12-myristate 13-acetate) but not glucagon, glucose
      dependent insulinotropic polypeptide (GIP), or epinephrine produced heterologous
      desensitization in vitro. MT-Ex-4 transgenic mice exhibited a reduced glycemic
      response to oral but not intraperitoneal glucose challenge following acute Ex-4
      administration. In contrast, no differences in glycemic excursion or plasma
      insulin were observed after 1 week of twice-daily Ex-4 administration to wild
      type versus MT-Ex-4 mice. Similarly, the levels of insulin, pdx-1, and GLP-1
      receptor mRNA transcripts were comparable in wild-type and MT-Ex-4 transgenic
      mice after 1 week of Ex-4 administration. However, repeated Ex-4 administration
      significantly reduced food intake in MT-Ex-4 but not in wild-type mice. These
      findings illustrate that although Ex-4 is more potent than native GLP-1 in
      producing GLP-1 receptor desensitization in vitro, chronic exposure to Ex-4 in
      normal or transgenic mice is not associated with significant downregulation of
      GLP-1 receptor-dependent responses coupled to glucose homeostasis in vivo.

PMID- 15561913
TI  - The high-fat diet-fed mouse: a model for studying mechanisms and treatment of
      impaired glucose tolerance and type 2 diabetes.
AB  - This study characterizes the high-fat diet-fed mouse as a model for impaired
      glucose tolerance (IGT) and type 2 diabetes. Female C57BL/6J mice were fed a high
      fat diet (58% energy by fat) or a normal diet (11% fat). Body weight was higher
      in mice fed the high-fat diet already after the first week, due to higher dietary
      intake in combination with lower metabolic efficiency. Circulating glucose
      increased after 1 week on high-fat diet and remained elevated at a level of
      approximately 1 mmol/l throughout the 12-month study period. In contrast,
      circulating insulin increased progressively by time. Intravenous glucose
      challenge revealed a severely compromised insulin response in association with
      marked glucose intolerance already after 1 week. To illustrate the usefulness of
      this model for the development of new treatment, mice were fed an orally active
      inhibitor of dipeptidyl peptidase-IV (LAF237) in the drinking water (0.3 mg/ml)
      for 4 weeks. This normalized glucose tolerance, as judged by an oral glucose
      tolerance test, in association with augmented insulin secretion. We conclude that
      the high-fat diet-fed C57BL/6J mouse model is a robust model for IGT and early
      type 2 diabetes, which may be used for studies on pathophysiology and development
      of new treatment.

PMID- 15561914
TI  - Suppression of Beta-cell secretion by somatostatin does not fully reverse the
      disproportionate proinsulinemia of type 2 diabetes.
AB  - Disproportionate hyperproinsulinemia is a feature of beta-cell dysfunction in
      type 2 diabetes. It has been hypothesized that this abnormality represents an
      intrinsic abnormality of the beta-cell and/or may result from an increase in beta
      cell secretory demand. To address this, six patients with type 2 diabetes and six
      age- and BMI-matched normal subjects received a combined 3-h insulin and
      somatostatin clamp to decrease beta-cell secretory demand. An arginine
      stimulation test was performed before and at the end of the clamp to measure beta
      cell peptide release. In keeping with the reduction in secretory demand, C
      peptide levels were suppressed by 60-80% during the clamp, as were proinsulin
      (PI) levels. The arginine-stimulated PI/C-peptide ratio decreased in the diabetic
      subjects from 4.4 +/- 1.5% before to 1.8 +/- 0.5% after the clamp (P < 0.01).
      This latter ratio was similar to that observed in the normal subjects before the
      somatostatin infusion (1.5 +/- 0.3%). In the normal subjects, after the clamp the
      PI/C-peptide ratio had decreased to 0.8 +/- 0.3% (P <0.01). Thus, the postclamp
      PI/C-peptide ratio in the subjects with type 2 diabetes was elevated compared
      with that in the normal subjects (P <0.05). Based on these observations, while
      relief of secretory demand on beta-cells by somatostatin decreases the
      disproportionate elevation in PI levels in patients with type 2 diabetes, the
      failure to normalize this measure suggests that an intrinsic abnormality of beta
      cell function exists in subjects with type 2 diabetes that may be aggravated by
      increased secretory demand.

PMID- 15561915
TI  - Stimulation of insulin secretion by intravenous bolus injection and continuous
      infusion of gastric inhibitory polypeptide in patients with type 2 diabetes and
      healthy control subjects.
AB  - A reduced insulinotropic effect of gastric inhibitory polypeptide (GIP) is a
      characteristic of patients with type 2 diabetes. It was the aim of this study to
      determine the response of insulin secretion to different GIP doses administered
      by intravenous bolus injection and via continuous infusion in both healthy
      subjects and patients with type 2 diabetes. Eight patients with type 2 diabetes
      and eight healthy subjects participated in a 240-min hyperglycemic clamp (140
      mg/dl) with intravenous infusion of placebo, GIP at a low dose, and GIP at a high
      dose, each administered continuously over 60 min. Boluses of placebo, 20 pmol
      GIP/kg, and 80 pmol GIP/kg were injected intravenously at 0, 60, and 120 min,
      respectively. Capillary and venous blood was drawn for glucose, insulin, C
      peptide, and GIP. Plasma insulin and C-peptide concentrations were lower in
      patients than in control subjects during all infusion periods. GIP bolus
      administration evoked a significant increase in plasma insulin levels in both
      patients with type 2 diabetes and healthy subjects. In contrast, the continuous
      GIP infusion led to a weak increase in insulin secretion in both healthy subjects
      and type 2 diabetic patients. The dose-response relationship for the increase in
      insulin secretion after GIP bolus administration was similar in both groups,
      although at different degrees of beta-cell function. The stimulation of insulin
      secretion by GIP is stronger after its bolus administration than during
      continuous infusion. Even though the insulin secretory capacity is generally
      impaired in patients with type 2 diabetes, the relative sensitivity of insulin
      secretion to a bolus administration of GIP is almost preserved. Therefore, the
      existence of a specific GIP receptor defect in type 2 diabetes appears unlikely.

PMID- 15561916
TI  - Signaling elements involved in the metabolic regulation of mTOR by nutrients,
      incretins, and growth factors in islets.
AB  - Mammalian target of rapamycin (mTOR) is a protein kinase that integrates signals
      from mitogens and the nutrients, glucose and amino acids, to regulate cellular
      growth and proliferation. Previous findings demonstrated that glucose robustly
      activates mTOR in an amino acid-dependent manner in rodent and human islets.
      Furthermore, activation of mTOR by glucose significantly increases rodent islet
      DNA synthesis that is abolished by rapamycin. Glucagon-like peptide-1 (GLP-1)
      agonists, through the production of cAMP, have been shown to enhance glucose
      dependent proinsulin biosynthesis and secretion and to stimulate cellular growth
      and proliferation. The objective of this study was to determine if the glucose
      dependent and cAMP-mediated mechanism by which GLP-1 agonists enhance beta-cell
      growth and proliferation is mediated, in part, through mTOR. Our studies
      demonstrated that forskolin-generated cAMP resulted in activation of mTOR at
      basal glucose concentrations as assessed by phosphorylation of S6K1, a downstream
      effector of mTOR. Conversely, an adenylyl cyclase inhibitor partially blocked
      glucose-induced S6K1 phosphorylation. Furthermore, the GLP-1 receptor agonist,
      Exenatide, dose-dependently enhanced phosphorylation of S6K1 at an intermediate
      glucose concentration (8 mmol/l) in a rapamycin-sensitive manner. To determine
      the mechanism responsible for this potentiation of mTOR, the effects of intra-
      and extracellular Ca2+ were examined. Glyburide, an inhibitor of ATP-sensitive K+
      channels (K(ATP) channels), provided partial activation of mTOR at basal glucose
      concentrations due to the influx of extracellular Ca2+, and diazoxide, an
      activator of KATP channels, resulted in partial inhibition of S6K1
      phosphorylation by 20 mmol/l glucose. Furthermore, Exenatide or forskolin
      reversed the inhibition by diazoxide, probably through mobilization of
      intracellular Ca2+ stores by cAMP. BAPTA, a chelator of intracellular Ca2+,
      resulted in inhibition of glucose-stimulated S6K1 phosphorylation due to a
      reduction in cytosolic Ca2+ concentrations. Selective blockade of glucose
      stimulated Ca2+ influx unmasked a protein kinase A (PKA)-sensitive component
      involved in the mobilization of intracellular Ca2+ stores, as revealed with the
      PKA inhibitor H-89. Overall, these studies support our hypothesis that incretin
      derived cAMP participates in the metabolic activation of mTOR by mobilizing
      intracellular Ca2+ stores that upregulate mitochondrial dehydrogenases and result
      in enhanced ATP production. ATP can then modulate KATP channels, serve as a
      substrate for adenylyl cyclase, and possibly directly regulate mTOR activation.

PMID- 15561917
TI  - Amylin agonists: a novel approach in the treatment of diabetes.
AB  - Amylin is a peptide hormone that is cosecreted with insulin from the pancreatic
      beta-cell and is thus deficient in diabetic people. It inhibits glucagon
      secretion, delays gastric emptying, and acts as a satiety agent. Amylin
      replacement could therefore possibly improve glycemic control in some people with
      diabetes. However, human amylin exhibits physicochemical properties predisposing
      the peptide hormone to aggregate and form amyloid fibers, which may play a part
      in beta-cell destruction in type 2 diabetes. This obviously makes it unsuitable
      for pharmacological use. A stable analog, pramlintide, which has actions and
      pharmacokinetic and pharmacodynamic properties similar to the native peptide, has
      been developed. The efficacy and safety of pramlintide administration has been
      tested in a vast number of clinical trials. Approximately 5,000 insulin-treated
      patients have received pramlintide and approximately 250 for > or =2 years. The
      aims of this review are to 1) briefly describe actions of amylin as demonstrated
      in animal and human models and 2) primarily review results from clinical trials
      with the amylin analog pramlintide.

PMID- 15561918
TI  - beta-cell function in obesity: effects of weight loss.
AB  - In nondiabetic subjects, obesity is associated with a modest expansion of beta
      cell mass, possibly amounting-according to the best available estimates-to 10-30%
      for each 10 kg of weight excess. Whether age of onset and duration of obesity,
      recent changes in body weight, and body fat distribution have any effect on beta
      cell mass in humans is unknown. Both fasting insulin secretion and the total
      insulin response to oral glucose have the following characteristics: 1) they
      increase with BMI in an approximately linear fashion, 2) both fat-free and fat
      mass are significant positive correlates, and 3) BMI exerts a positive effect
      separate from that of insulin resistance (i.e., obesity may be a state of primary
      insulin hypersecretion). The mechanisms are currently unknown, though chronic
      small increments in plasma glucose may play a role. In contrast, dynamic
      properties of beta-cell function, such as glucose sensitivity (i.e., dose
      response function), rate sensitivity, and potentiation, do not appear to be
      substantially altered by the presence of obesity, body fat distribution, or
      insulin resistance as long as glucose tolerance is maintained. Weight loss, by
      diet or restrictive bariatric surgery, is associated with consensual decrements
      in insulin resistance and insulin hypersecretion. The latter, however, seems to
      be more persistent, suggesting that the postobese state may reproduce the primary
      insulin hypersecretion of the obese state. Malabsorptive bariatric surgery, in
      contrast, normalizes insulin sensitivity and abolishes insulin hypersecretion
      even before achievement of ideal body weight. Lipid-triggered messages from the
      gastrointestinal tract to the insulin target tissues and endocrine pancreas are
      the subject of intense investigation.

PMID- 15561919
TI  - Prevention of type 2 diabetes: insulin resistance and beta-cell function.
AB  - Type 2 diabetes is increasing worldwide in epidemic proportions. Its associated
      morbidity and mortality is imposing a major burden on the health care system.
      Based on a better understanding of the pathophysiology of glucose intolerance,
      clinical trials on the prevention of diabetes have been performed. It has now
      been demonstrated that diet and exercise, metformin, acarbose, and troglitazone
      can prevent or at least delay the development of diabetes in subjects with
      impaired glucose tolerance (IGT). It is now generally accepted that insulin
      resistance and beta-cell dysfunction are major factors involved in the
      development of diabetes. The relative contribution of insulin resistance versus
      beta-cell dysfunction on the pathogenesis of diabetes has aroused much debate.
      These two processes should be studied in relation to one another: their
      relationship is best described as hyperbolic in nature. When this relationship is
      taken into consideration, it becomes evident that subjects at risk of developing
      type 2 diabetes have beta-cell dysfunction before they develop glucose
      intolerance. Insulin resistance may be mostly explained by the presence of
      obesity and accelerate the progression to diabetes in subjects with the
      propensity to beta-cell failure. By the time hyperglycemia occurs, impairment in
      both insulin sensitivity and insulin secretion are present. There are still few
      data on insulin sensitivity and insulin secretion from the trials on the
      prevention of diabetes. The few data that we do have suggest that most
      interventions mostly have an effect on insulin resistance. By reducing insulin
      resistance, they protect and preserve the beta-cell function. No intervention has
      yet shown any direct effect on beta-cell function.

PMID- 15561920
TI  - Intensive integrated therapy of type 2 diabetes: implications for long-term
      prognosis.
AB  - The macro- and microvascular burden of type 2 diabetes is well established. A
      number of recent single risk factor intervention trials targeting hyperglycemia,
      dyslipidemia, hypertension, procoagulation, microalbumuria, and existing
      cardiovascular disorders have, however, shown major beneficial effects on long
      term outcome. The results from these studies are anticipated to change the future
      management of type 2 diabetes, and most of the updated national guidelines for
      the treatment of type 2 diabetes recommend a multipronged approach driven by
      ambitious treatment targets. The outcome of this intensive integrated therapy
      has, however, only been investigated in a few studies of patients with type 2
      diabetes. One of these trials, the Steno-2 Study, showed that intensive
      intervention for an average of 7.8 years cuts cardiovascular events as well as
      nephropathy, retinopathy, and autonomic neuropathy by about half when compared
      with a conventional multifactorial treatment. The challenge for now is to ensure
      that the trial experiences are widely adopted in daily clinical practice.

PMID- 15561921
TI  - Pathways in beta-cell stimulus-secretion coupling as targets for therapeutic
      insulin secretagogues.
AB  - Physiologically, insulin secretion is subject to a dual, hierarchal control by
      triggering and amplifying pathways. By closing ATP-sensitive K+ channels (KATP
      channels) in the plasma membrane, glucose and other metabolized nutrients
      depolarize beta-cells, stimulate Ca2+ influx, and increase the cytosolic
      concentration of free Ca2+ ([Ca2+]i), which constitutes the indispensable
      triggering signal to induce exocytosis of insulin granules. The increase in beta
      cell metabolism also generates amplifying signals that augment the efficacy of
      Ca2+ on the exocytotic machinery. Stimulatory hormones and neurotransmitters
      modestly increase the triggering signal and strongly activate amplifying pathways
      biochemically distinct from that set into operation by nutrients. Many drugs can
      increase insulin secretion in vitro, but only few have a therapeutic potential.
      This review identifies six major pathways or sites of stimulus-secretion coupling
      that could be aimed by potential insulin-secreting drugs and describes several
      strategies to reach these targets. It also discusses whether these perspectives
      are realistic or theoretical only. These six possible beta-cell targets are 1)
      stimulation of metabolism, 2) increase of [Ca2+]i by closure of K+ ATP channels,
      3) increase of [Ca2+]i by other means, 4) stimulation of amplifying pathways, 5)
      action on membrane receptors, and 6) action on nuclear receptors. The theoretical
      risk of inappropriate insulin secretion and, hence, of hypoglycemia linked to
      these different approaches is also envisaged.

PMID- 15561922
TI  - Integration of ATP, cAMP, and Ca2+ signals in insulin granule exocytosis.
AB  - Intracellular ATP, cAMP, and Ca2+ are major signals involved in the regulation of
      insulin secretion in the pancreatic beta-cell. We recently found that the ATP
      sensitive K+ channel (KATP channel) as an ATP sensor, cAMP-GEFII as a cAMP
      sensor, Piccolo as a Ca2+ sensor, and L-type voltage-dependent Ca2+ channel
      (VDCC) can interact with each other. In the present study, we examined the
      effects of cAMP and ATP on the interaction of cAMP-GEFII and sulfonylurea
      receptor-1 (SUR1). Interaction of cAMP-GEFII with SUR1 was inhibited by the cAMP
      analog 8-bromo-cAMP but not by ATP, and the inhibition by 8-bromo-cAMP persisted
      in the presence of ATP. In addition, SUR1, cAMP-GEFII, and Piccolo could form a
      complex. Piccolo also interacted with the alpha1 1.2 subunit of VDCC in a Ca2+
      independent manner. These data suggest that the interactions of the KATP channel,
      cAMP-GEFII, Piccolo, and L-type VDCC are regulated by intracellular signals such
      as cAMP and Ca2+ and that the ATP, cAMP, and Ca2+ signals are integrated at a
      specialized region of pancreatic beta-cells.

PMID- 15561923
TI  - Metabolic syndrome and robustness tradeoffs.
AB  - The metabolic syndrome is a highly complex breakdown of normal physiology
      characterized by obesity, insulin resistance, hyperlipidemia, and hypertension.
      Type 2 diabetes is a major manifestation of this syndrome, although increased
      risk for cardiovascular disease (CVD) often precedes the onset of frank clinical
      diabetes. Prevention and cure for this disease constellation is of major
      importance to world health. Because the metabolic syndrome affects multiple
      interacting organ systems (i.e., it is a systemic disease), a systems-level
      analysis of disease evolution is essential for both complete elucidation of its
      pathophysiology and improved approaches to therapy. The goal of this review is to
      provide a perspective on systems-level approaches to metabolic syndrome, with
      particular emphasis on type 2 diabetes. We consider that metabolic syndromes take
      over inherent dynamics of our body that ensure robustness against unstable food
      supply and pathogenic infections, and lead to chronic inflammation that
      ultimately results in CVD. This exemplifies how trade-offs between robustness
      against common perturbations (unstable food and infections) and fragility against
      unusual perturbations (high-energy content foods and low-energy utilization
      lifestyle) is exploited to form chronic diseases. Possible therapeutic approaches
      that target fragility of emergent robustness of the disease state have been
      discussed. A detailed molecular interaction map for adipocyte, hepatocyte,
      skeletal muscle cell, and pancreatic beta-cell cross-talk in the metabolic
      syndrome can be viewed at http://www.systems-biology.org/001/003.html.

PMID- 15561924
TI  - P2Y purinergic potentiation of glucose-induced insulin secretion and pancreatic
      beta-cell metabolism.
AB  - Purine nucleotides and their analogs increase insulin secretion through
      activation of pancreatic beta-cell P2Y receptors. The present study aimed at
      determining the role of glucose metabolism in the response to P2Y agonists and
      whether ATP-activated K+ channels (KATP channels) are involved in this response.
      The experiments were performed in the rat isolated pancreas, perfused with a
      Krebs-bicarbonate buffer supplemented with 2 g/l bovine serum albumin under
      dynamic glucose conditions from 5 mmol/l baseline to 11 mmol/l. ADPbetaS (0.5
      micromol/l) was selected as a stable and selective P2Y agonist. This compound,
      ineffective on the 5 mmol/l glucose background, induced a significant threefold
      increase in insulin release triggered by the glucose challenge. The effect of
      ADPbetaS was markedly reduced (P <0.001) in the presence of an inhibitor of
      glucose metabolism. In addition to glucose, the ADP analog also amplified the
      beta-cell insulin response to 15 mmol/l methyl pyruvate (P <0.05), but it was
      ineffective on the insulin response to 2.5 mmol/l methyl succinate. A
      nonmetabolic stimulus was applied using tolbutamide (185 micromol/l). Insulin
      secretion induced by the KATP channel blocker was strongly reinforced by ADPbetaS
      (P <0.001), which prompted us to check a possible interplay of KATP channels in
      the effect of ADPbetaS. In the presence of diazoxide 250 micromol/l and 21 mmol/l
      KCl, ADPbetaS still amplified the second phase of glucose-induced insulin
      secretion (P <0.001). We conclude that P2Y receptor activation is able to promote
      insulin secretion through a mechanism, involving beta-cell metabolism and a rise
      in intracellular calcium; this effect does not result from a direct inhibitory
      effect on KATP channels.

PMID- 15561925
TI  - AMP-activated protein kinase: a new beta-cell glucose sensor?: Regulation by
      amino acids and calcium ions.
AB  - Stimulation of AMP-activated protein kinase (AMPK) in skeletal muscle and liver
      is seen as an exciting prospect for the treatment of type 2 diabetes. However, we
      have recently demonstrated that changes in AMPK activity accompany the exposure
      of pancreatic islet beta-cells to elevated glucose concentrations and may be
      involved in the activation of insulin secretion. Here, we discuss this hypothesis
      and explore the potential role of changes in AMPK activity in the actions of
      other secretagogues. Amino acids decreased AMPK activity in MIN6 beta-cells with
      an order of potency for inhibition: arg=leu < gln= leu + glu < glucose, which was
      closely correlated with the stimulation of insulin release (r2=0.76). By
      contrast, increases in intracellular Ca2+ concentration provoked by cell
      depolarization with KCl activated AMPK in the face of increased free
      intracellular ATP concentrations. Elevation of intracellular cAMP levels with
      isobutylmethylxanthine or forskolin had no effect on AMPK activity. We conclude
      that metabolizable amino acids regulate AMPK in the beta-cell via increases in
      the cytosolic ATP/AMP ratio and via phosphorylation by the upstream kinase LKB1.
      Intracellular Ca2+ ions may activate AMPK by calmodulin kinase 1 kinase-mediated
      phosphorylation. The latter may act as a novel feedback mechanism to inhibit
      excessive insulin secretion under some circumstances.

PMID- 15561926
TI  - Liver X receptor activation stimulates insulin secretion via modulation of
      glucose and lipid metabolism in pancreatic beta-cells.
AB  - Liver X receptors (LXRs) alpha and beta, transcription factors of a nuclear
      hormone receptor family, are expressed in pancreatic islets as well as glucagon
      secreting and insulin-secreting cell lines. Culture of pancreatic islets or
      insulin-secreting MIN6 cells with a LXR specific agonist T0901317 caused an
      increase in glucose-dependent insulin secretion and islet insulin content. The
      stimulatory effect of T0901317 on insulin secretion was observed only after >72 h
      of islet culture with the compound. In MIN6 cells, T0901317 increased protein
      expression of lipogenic enzymes, fatty acid synthase, and acetyl-CoA carboxylase.
      LXR activation also produced an increase in glucokinase protein and pyruvate
      carboxylase (PC) activity levels. The PC inhibitor phenylacetic acid abolished
      the increase in insulin secretion in cells treated with T0901317. The results
      suggest that LXRs can control insulin secretion and biosynthesis via regulation
      of glucose and lipid metabolism in pancreatic beta-cells.

PMID- 15561927
TI  - Effect of PPAR-gamma activation and inhibition on glucose-stimulated insulin
      release in INS-1e cells.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma is expressed in human
      beta-cells and in the rat beta-cell line INS-1. Previous studies have suggested
      that PPAR-gamma agonism (e.g., thiazolidinediones) enhances glucose-stimulated
      insulin secretion (GSIS) from islets or INS-1 cells. We tested the direct effect
      on insulin release by INS-1e of a PPAR-gamma agonist (Ro4389679-000-001 at 0.2
      and 0.4 micromol/l) and a PPAR-gamma antagonist (SR202 at 0.2 and 0.4 mmol/l).
      Cells were incubated in 11 mmol/l glucose for 96 h and then challenged with 3.3,
      7.5, 11.0, and 20.0 mmol/l glucose for 1 h. Under these control conditions,
      insulin concentrations in the medium rose from 19 +/- 4 ng/ml (mean +/- SE) to 82
      +/- 5, 107 +/- 11, and 103 +/- 10 ng/ml (P <0.0001 by ANOVA). Preincubation for
      48 h with the PPAR-gamma agonist potentiated GSIS (to 154 +/- 14 and 156 +/- 12
      ng/ml at 20 mmol/l glucose, P <0.01). Cell insulin content was not altered by
      either acute glucose challenge or PPAR-gamma agonist coincubation. Preincubation
      for 48 h with SR202 at the higher dose caused a 30% inhibition of GSIS, with no
      change in cell insulin contents. When cells were preincubated with 11 mmol/l
      glucose plus 1 mmol/l oleate, GSIS was significantly potentiated (by 30%, P
      <0.0001); adding Ro4389679-000-001 or SR202 to these preincubations reduced GSIS
      to the respective levels seen in the absence of oleate (P <0.0001 for both
      effects). In conclusion, INS-1e cells display a PPAR-gamma tone that is
      symmetrically modulated and competitively stimulated by oleate.

PMID- 15561928
TI  - Impact of adenoviral transduction with SREBP1c or AMPK on pancreatic islet gene
      expression profile: analysis with oligonucleotide microarrays.
AB  - Accumulation of triglyceride in islets may contribute to the loss of glucose
      stimulated insulin secretion (GSIS) in some forms of type 2 diabetes (Diraison et
      al., Biochem J 373:769-778, 2004). Here, we use adenoviral vectors and
      oligonucleotide microarrays to determine the effects of the forced expression of
      SREBP1c on the gene expression profile of rat islets. Sterol regulatory element
      binding protein-1c (SREBP1c) overexpression led to highly significant (P <0.1
      with respect to null adenovirus) changes in the expression of 1,238 genes or
      expressed sequence tags, of which 1,180 (95.3%) were upregulated. By contrast,
      overexpression of constitutively active AMP-activated protein kinase (AMPK),
      expected to promote lipolysis, altered the expression of 752 genes, of which 702
      (93%) were upregulated. To identify specific targets for SREBP1c or AMPK, we
      eliminated messages that were 1) affected in the same direction by the expression
      of either protein, 2) changed by less than twofold, or 3) failed a positive false
      discovery test; 206 SREBP1c-regulated genes (195; 95% upregulated) and 48 AMPK
      regulated genes (33; 69% upregulated) remained. As expected, SREBP1c-induced
      genes included those involved in cholesterol (6), fatty acid (3), and eicosanoid
      synthesis. Interestingly, somatostatin receptor (sstr1) expression was increased
      by SREBP1c, whereas AMPK induced the expression of peptide YY, the early
      endocrine pancreas marker.

PMID- 15561929
TI  - Beta-cell-targeted expression of a dominant-negative mutant of hepatocyte nuclear
      factor-1alpha in mice: diabetes model with beta-cell dysfunction partially
      rescued by nonglucose secretagogues.
AB  - We studied islet function in mice with beta-cell-targeted expression of a
      dominant-negative mutant of hepatocyte nuclear factor (HNF)-1alpha. At age 2-3
      months, anesthetized transgenic and wild-type male mice underwent an intravenous
      glucose (1 g/kg) tolerance test (IVGTT). It was found that transgenic mice had an
      abolished insulin response in association with severe glucose intolerance. In
      other tests, the 5-min insulin response to intravenous arginine was impaired by
      79% (P=0.032) and the 15-min insulin response to gastric glucose was suppressed
      by 97% (P=0.006). In islets incubated for 60 min, the insulin response to glucose
      (3.3-22.2 mmol/l) was impaired by >80% in transgenic mice. In contrast, insulin
      responses to nonglucose secretagogues were only partially suppressed (to GLP-1
      [100 nmol/l] by 40%, to carbachol [1 micromol/l] by 20%, and to palmitate [0.5
      mmol/l] by 15%), whereas the response to depolarization by KCl (50 mmol/l) was
      not reduced. Finally, the IVGTT data insulin sensitivity in transgenic mice was
      not significantly different from that of wild-type mice. Thus, mice with targeted
      suppression of beta-cell HNF-1alpha represent a good diabetes model exhibiting
      severely impaired insulin secretion after glucose with marked glucose
      intolerance. In contrast, the insulin responses to nonglucose stimuli are not
      suppressed when the islet insulin content is taken into account.

PMID- 15561930
TI  - The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of
      insulin signaling in pancreatic beta-cells.
AB  - Defects in insulin secretion, resulting from loss of function or destruction of
      pancreatic beta-cells, trigger diabetes. Interleukin (IL)-1beta is a
      proinflammatory cytokine that is involved in type 1 and type 2 diabetes
      development and impairs beta-cell survival and function. Because effective
      insulin signaling is required for the optimal beta-cell function, we assessed the
      effect of IL-1beta on the insulin pathway in a rat pancreatic beta-cell line. We
      show that IL-1beta decreases insulin-induced tyrosine phosphorylation of the
      insulin receptor (IR) and insulin receptor substrate (IRS) proteins as well as
      phosphatidylinositol 3-kinase (PI3K) activation, and that this action is not due
      to the IL-1beta-dependent nitric oxide (NO) production in RINm5F cells. We next
      analyzed if suppressor of cytokine signaling (SOCS)-3, which can be induced by
      multiple cytokines and which we identified as an insulin action inhibitor, was
      implicated in the IL-1beta inhibitory effect on insulin signaling in these cells.
      We show that IL-1beta increases SOCS-3 expression and induces SOCS-3/IR complex
      formation in RINm5F cells. Moreover, we find that ectopically expressed SOCS-3
      associates with the IR and reduces insulin-dependent IR autophosphorylation and
      IRS/PI3K pathway in a way comparable to IL-1beta treatment in RINm5F cells. We
      propose that IL-1beta decreases insulin action in beta-cells through the
      induction of SOCS-3 expression, and that this effect potentially alters insulin
      induced beta-cell survival.

PMID- 15561931
TI  - Age-dependent influences on the origins of autoimmune diabetes: evidence and
      implications.

PMID- 15561932
TI  - Exercise-induced changes in insulin and glucagon are not required for enhanced
      hepatic glucose uptake after exercise but influence the fate of glucose within
      the liver.
AB  - To test whether pancreatic hormonal changes that occur during exercise are
      necessary for the postexercise enhancement of insulin-stimulated net hepatic
      glucose uptake, chronically catheterized dogs were exercised on a treadmill or
      rested for 150 min. At the onset of exercise, somatostatin was infused into a
      peripheral vein, and insulin and glucagon were infused in the portal vein to
      maintain basal levels (EX-Basal) or simulate the response to exercise (EX-Sim).
      Glucose was infused as needed to maintain euglycemia during exercise. After
      exercise or rest, somatostatin infusion was continued in exercised dogs and
      initiated in dogs that had remained sedentary. In addition, basal glucagon,
      glucose, and insulin were infused in the portal vein for 150 min to create a
      hyperinsulinemic-hyperglycemic clamp in EX-Basal, EX-Sim, and sedentary dogs.
      Steady-state measurements were made during the final 50 min of the clamp. During
      exercise, net hepatic glucose output (mg x kg(-1) x min(-1)) rose in EX-Sim (7.6
      +/- 2.8) but not EX-Basal (1.9 +/- 0.3) dogs. During the hyperinsulinemic
      hyperglycemic clamp that followed either exercise or rest, net hepatic glucose
      uptake (mg x kg(-1) x min(-1)) was elevated in both EX-Basal (4.0 +/- 0.7) and EX
      Sim (4.6 +/- 0.5) dogs compared with sedentary dogs (2.0 +/- 0.3). Despite this
      elevation in net hepatic glucose uptake after exercise, glucose incorporation
      into hepatic glycogen, determined using [3-3H]glucose, was not different in EX
      Basal and sedentary dogs, but was 50 +/- 30% greater in EX-Sim dogs. Exercise
      induced changes in insulin and glucagon, and consequent glycogen depletion, are
      not required for the increase in net hepatic glucose uptake after exercise but
      result in a greater fraction of the glucose consumed by the liver being directed
      to glycogen.

PMID- 15561933
TI  - Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes.
AB  - Decreased skeletal muscle glucose disposal and increased endogenous glucose
      production (EGP) contribute to postprandial hyperglycemia in type 2 diabetes, but
      the contribution of hepatic glycogen metabolism remains uncertain. Hepatic
      glycogen metabolism and EGP were monitored in type 2 diabetic patients and
      nondiabetic volunteer control subjects (CON) after mixed meal ingestion and
      during hyperglycemic-hyperinsulinemic-somatostatin clamps applying 13C nuclear
      magnetic resonance spectroscopy (NMRS) and variable infusion dual-tracer
      technique. Hepatocellular lipid (HCL) content was quantified by 1H NMRS. Before
      dinner, hepatic glycogen was lower in type 2 diabetic patients (227 +/- 6 vs.
      CON: 275 +/- 10 mmol/l liver, P < 0.001). After meal ingestion, net synthetic
      rates were 0.76 +/- 0.16 (type 2 diabetic patients) and 1.36 +/- 0.15 mg x kg(-1)
      x min(-1) (CON, P < 0.02), resulting in peak concentrations of 283 +/- 15 and 360
      +/- 11 mmol/l liver. Postprandial rates of EGP were approximately 0.3 mg x kg(-1)
      x min(-1) (30-170 min; P < 0.05 vs. CON) higher in type 2 diabetic patients.
      Under clamp conditions, type 2 diabetic patients featured approximately 54% lower
      (P < 0.03) net hepatic glycogen synthesis and approximately 0.5 mg x kg(-1) x
      min(-1) higher (P < 0.02) EGP. Hepatic glucose storage negatively correlated with
      HCL content (R = -0.602, P < 0.05). Type 2 diabetic patients exhibit 1) reduction
      of postprandial hepatic glycogen synthesis, 2) temporarily impaired suppression
      of EGP, and 3) no normalization of these defects by controlled hyperglycemic
      hyperinsulinemia. Thus, impaired insulin sensitivity and/or chronic
      glucolipotoxicity in addition to the effects of an altered insulin-to-glucagon
      ratio or increased free fatty acids accounts for defective hepatic glycogen
      metabolism in type 2 diabetic patients.

PMID- 15561934
TI  - Hepatic PTP-1B expression regulates the assembly and secretion of apolipoprotein
      B-containing lipoproteins: evidence from protein tyrosine phosphatase-1B
      overexpression, knockout, and RNAi studies.
AB  - Protein tyrosine phosphatase-1B (PTP-1B) plays an important role in regulation of
      insulin signal transduction, and modulation of PTP-1B expression seems to have a
      profound effect on insulin sensitivity and diet-induced weight gain. The
      molecular link between PTP-1B expression and metabolic dyslipidemia, a major
      complication of insulin resistance, was investigated in the present study using
      PTP-1B knockout mice as well as overexpression and suppression of PTP-1B. Chronic
      fructose feeding resulted in a significant increase in plasma VLDL in wild-type
      mice but not in PTP-1B knockout mice. Lipoprotein profile analysis of plasma from
      PTP-1B knockout mice revealed a significant reduction in apolipoprotein B
      (apoB100) lipoproteins, associated with reduced hepatic apoB100 secretion from
      isolated primary hepatocytes. In addition, treatment of cultured hepatoma cells
      with PTP-1B siRNA reduced PTP-1B mass by an average of 41% and was associated
      with a 53% decrease in secretion of metabolically labeled apoB100. Conversely,
      adenoviral-mediated overexpression of PTP-1B in HepG2 cells downregulated the
      phosphorylation of insulin receptor and insulin receptor substrate-1 and caused
      increases in cellular and secreted apoB100 as a result of increased intracellular
      apoB100 stability. Collectively, these findings suggest that PTP-1B expression
      level is a key determinant of hepatic lipoprotein secretion, and its
      overexpression in the liver can be sufficient to induce VLDL overproduction and
      the transition to a metabolic dyslipidemic state.

PMID- 15561935
TI  - LRb-STAT3 signaling is required for the neuroendocrine regulation of energy
      expenditure by leptin.
AB  - Secretion of leptin from adipose tissue communicates body energy status to the
      neuroendocrine system by activating the long form of the leptin receptor (LRb).
      Lack of leptin or LRb (as in db/db mice) results in obesity that stems from the
      combined effects of hyperphagia and decreased energy expenditure. We have
      previously generated mice in which LRb is replaced with a mutant LRb (LRbS1138)
      that specifically disrupts LRb-->STAT3 (signal transducer and activator of
      transcription-3) signaling; mice homozygous for this mutant (s/s) display
      increased feeding and are obese. We have now examined energy expenditure in s/s
      and db/db mice. Consistent with the increased lean body mass of s/s animals,
      locomotor activity and acute cold tolerance (partly a measure of shivering
      thermogenesis) in s/s mice were modestly but significantly improved compared with
      db/db mice, although they were decreased compared with wild-type mice. Total and
      resting metabolic rates were similarly depressed in s/s and db/db mice, however.
      Indeed, s/s and db/db mice display similar reductions in thyroid function and
      brown adipose tissue expression of uncoupling protein-1, which is regulated by
      sympathetic nervous system (SNS) tone. Thus, the LRb-->STAT3 signal is central to
      both the control of energy expenditure by leptin and the neuroendocrine
      regulation of the SNS and the thyroid axis.

PMID- 15561936
TI  - The alpha2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in
      skeletal muscle and is responsive to glucose loading.
AB  - The 5'AMP-activated protein kinase (AMPK) is a potential antidiabetic drug
      target. Here we show that the pharmacological activation of AMPK by 5
      aminoimidazole-1-beta-4-carboxamide ribofuranoside (AICAR) leads to inactivation
      of glycogen synthase (GS) and phosphorylation of GS at Ser 7 (site 2). In muscle
      of mice with targeted deletion of the alpha2-AMPK gene, phosphorylation of GS
      site 2 was decreased under basal conditions and unchanged by AICAR treatment. In
      contrast, in alpha1-AMPK knockout mice, the response to AICAR was normal. Fuel
      surplus (glucose loading) decreased AMPK activation by AICAR, but the
      phosphorylation of the downstream targets acetyl-CoA carboxylase-beta and GS was
      normal. Fractionation studies suggest that this suppression of AMPK activation
      was not a direct consequence of AMPK association with membranes or glycogen,
      because AMPK was phosphorylated to a greater extent in response to AICAR in the
      membrane/glycogen fraction than in the cytosolic fraction. Thus, the downstream
      action of AMPK in response to AICAR was unaffected by glucose loading, whereas
      the action of the kinase upstream of AMPK, as judged by AMPK phosphorylation, was
      decreased. The fact that alpha2-AMPK is a GS kinase that inactivates GS while
      simultaneously activating glucose transport suggests that a balanced view on the
      suitability for AMPK as an antidiabetic drug target should be taken.

PMID- 15561937
TI  - G-protein signaling participates in the development of diabetic cardiomyopathy.
AB  - Diabetic patients develop a cardiomyopathy that consists of ventricular
      hypertrophy and diastolic dysfunction. Although the pathogenesis of this
      condition is poorly understood, previous studies implicated abnormal G-protein
      activation. In this work, mice with cardiac overexpression of the transcription
      factor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) were
      examined as a model of diabetic cardiomyopathy. PPAR-alpha transgenic mice
      develop spontaneous cardiac hypertrophy, contractile dysfunction, and "fetal"
      gene induction. We examined the role of abnormal G-protein activation in the
      pathogenesis of cardiac dysfunction by crossing PPAR-alpha mice with transgenic
      mice with cardiac-specific overexpression of regulator of G-protein signaling
      subtype 4 (RGS4), a GTPase activating protein for Gq and Gi. Generation of
      compound transgenic mice demonstrated that cardiac RGS4 overexpression
      ameliorated the cardiomyopathic phenotype that occurred as a result of PPAR-alpha
      overexpression without affecting the metabolic abnormalities seen in these
      hearts. Next, transgenic mice with increased or decreased cardiac Gq signaling
      were made diabetic by injection with streptozotocin (STZ). RGS4 transgenic mice
      were resistant to STZ-induced cardiac fetal gene induction. Transgenic mice with
      cardiac-specific expression of mutant Galphaq, Galphaq-G188S, that is resistant
      to RGS protein action were sensitized to the development of STZ-induced cardiac
      fetal gene induction and bradycardia. These results establish that Gq-mediated
      signaling plays a critical role in the pathogenesis of diabetic cardiomyopathy.

PMID- 15561938
TI  - Pancreatic polypeptide is involved in the regulation of body weight in pima
      Indian male subjects.
AB  - Pancreatic polypeptide (PP) is released from the pancreas in response to a meal.
      In humans, low-circulating PP levels have been observed in obesity, and
      administration of pharmacological doses of PP has been shown to decrease food
      intake. The aim of the present study was to investigate whether low circulating
      PP is associated with weight gain in Pima Indians. Plasma PP concentrations were
      measured after an overnight fast and 30 min after a standardized mixed meal in 33
      nondiabetic male subjects who had a follow-up visit 4.9 +/- 2.5 years later.
      Cross-sectionally, fasting and postprandial PP levels were negatively associated
      with body size and adiposity. Prospectively, the change in PP response to the
      meal was negatively associated with the change in body weight (r = -0.53, P =
      0.002). In contrast, a high fasting PP level was positively associated with
      change in body weight (r = 0.45, P = 0.009). In conclusion, our results provide
      evidence that, even within the physiological range, PP contributes to the
      regulation of energy balance in humans. However this contribution appears to be
      more complex than anticipated because of the opposite effect of fasting and
      postprandial PP on the risk of future weight gain.

PMID- 15561939
TI  - Fibroblast growth factor 1: a key regulator of human adipogenesis.
AB  - Obesity, with its related problems, is recognized as the fastest growing disease
      epidemic facing the world, yet we still have limited insight into the regulation
      of adipose tissue mass in humans. We have previously shown that adipose-derived
      microvascular endothelial cells (MVECs) secrete a factor(s) that increases
      proliferation of human preadipocytes. We now demonstrate that coculture of human
      preadipocytes with MVECs significantly increases preadipocyte differentiation,
      evidenced by dramatically increased triacylglycerol accumulation and glycerol-3
      phosphate dehydrogenase activity compared with controls. Subsequent analysis
      identified fibroblast growth factor (FGF)-1 as an adipogenic factor produced by
      MVECs. Expression of FGF-1 was demonstrated in MVECs but not in preadipocytes,
      while preadipocytes were shown to express FGF receptors 1-4. The proliferative
      effect of MVECs on human preadipocytes was blocked using a neutralizing antibody
      specific for FGF-1. Pharmacological inhibition of FGF-1 signaling at multiple
      steps inhibits preadipocyte replication and differentiation, supporting the key
      adipogenic role of FGF-1. We also show that 3T3-L1 cells, a highly efficient
      murine model of adipogenesis, express FGF-1 and, unlike human preadipocytes,
      display no increased differentiation potential in response to exogenous FGF-1.
      Conversely, FGF-1-treated human preadipocytes proliferate rapidly and
      differentiate with high efficiency in a manner characteristic of 3T3-L1 cells. We
      therefore suggest that FGF-1 is a key human adipogenic factor, and these data
      expand our understanding of human fat tissue growth and have significant
      potential for development of novel therapeutic strategies in the prevention and
      management of human obesity.

PMID- 15561940
TI  - Islet graft assessment in the Edmonton Protocol: implications for predicting long
      term clinical outcome.
AB  - The success of the Edmonton Protocol for islet transplantation has provided new
      hope in the treatment of type 1 diabetes. This study reports on the assessment of
      83 human islet grafts transplanted using the Edmonton Protocol since 1999.
      Cellular composition, as assessed by immunohistochemistry, showed a lower islet
      purity (approximately 40%) than has been reported in previous studies using
      dithizone staining to quantitate islet equivalents. Furthermore, grafts were
      found to contain substantial populations of exocrine and ductal tissue. Total
      cellular insulin transplanted was 8,097.6 +/- 3,164.4 microg/patient, and was
      significantly lower in bottom gradient layer grafts than top gradient layer or
      whole/combined grafts (P < 0.0005). A static incubation test for islet function
      gave a stimulation index of 3-4, although this measure did not correlate with
      posttransplant metabolic outcome. Furthermore, we confirmed a previously reported
      trend in which donor age affects islet yield and purity. It is important to note
      that a significant positive correlation was observed between the number of islet
      progenitor (ductal-epithelial) cells transplanted and long-term metabolic success
      as assessed an by intravenous glucose tolerance test at approximately 2 years
      posttransplant. In summary, careful assessment of islet graft composition is
      needed in a clinical transplantation program to accurately estimate islet purity
      and assess the contribution of other cell types present, such as islet progenitor
      cells.

PMID- 15561941
TI  - Absence of lymph nodes in NOD mice treated with lymphotoxin-beta receptor
      immunoglobulin protects from diabetes.
AB  - Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-beta receptor
      immunoglobulin fusion protein (LTbetaR-Ig) or control human immunoglobulin on
      days embryonic day 11 (E11) and E14, and offspring were followed for the
      development of anti-beta-cell antibodies, islet pathology, and hyperglycemia. The
      development of anti-beta-cell surface antibodies was abrogated in treated mice
      compared with controls. Autopsy examination of the mice at 30 weeks of age
      revealed normal development of secondary lymphoid structures in the control
      animals; however, mice treated with LTbetaR-Ig had no axillary, inguinal,
      popliteal, or peripancreatic lymph nodes. Histological examination of the
      pancreata of the control mice revealed a severe and destructive mononuclear
      cellular infiltrate in the islets, whereas the islets of the LTbetaR-Ig-treated
      mice were devoid of any insulitis. None of the LTbetaR-Ig-treated mice (n = 22)
      developed diabetes; in contrast, 80% of the control mice (n = 46) developed
      diabetes at 1 year of age. The LTbetaR-Ig-treated mice did not contain
      diabetogenic T-cells. However, the treated mice developed diabetes upon
      inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune
      diabetes, secondary lymphoid structures, most likely the peripancreatic lymph
      nodes, were essential for the development of pathologic anti-beta-cell
      autoimmunity.

PMID- 15561942
TI  - Characterization of mice doubly transgenic for parathyroid hormone-related
      protein and murine placental lactogen: a novel role for placental lactogen in
      pancreatic beta-cell survival.
AB  - Transgenic overexpression of either parathyroid hormone-related peptide (PTHrP)
      or mouse placental lactogen type 1 (mPL1) in pancreatic beta-cells, using the rat
      insulin II promoter (RIP), results in islet hyperplasia either through prolonged
      beta-cell survival or through increased beta-cell proliferation and hypertrophy,
      respectively. For determining whether the two proteins might exert complementary,
      additive, or synergistic effects on islet mass and function when simultaneously
      overexpressed in beta-cells in vivo, RIP-PTHrP and RIP-mPL1 mice were crossed to
      generate mice doubly transgenic for PTHrP and mPL1. These double-transgenic mice
      displayed marked islet hyperplasia (threefold), hypoglycemia, increased beta-cell
      proliferation (threefold), and resistance to the diabetogenic and cytotoxic
      effects of streptozotocin compared with their normal siblings. Although the
      phenotype of the double-transgenic mice was neither additive nor synergistic
      relative to their single-transgenic counterparts, it was indeed complementary,
      yielding the maximal salutary phenotypic features of both individual transgenes.
      Finally, mPL1, for the first time, was shown to exert a protective effect on the
      survival of beta-cells, placing it among the few proteins that can improve
      function and proliferation and prolong the survival of beta-cells. Placental
      lactogen 1 is an attractive target for future therapeutic strategies in diabetes.

PMID- 15561943
TI  - Pancreatic-specific inactivation of IGF-I gene causes enlarged pancreatic islets
      and significant resistance to diabetes.
AB  - The dogma that IGF-I stimulates pancreatic islet growth has been challenged by
      combinational targeting of IGF or IGF-IR (IGF receptor) genes as well as beta
      cell-specific IGF-IR gene deficiency, which caused no defect in islet cell
      growth. To assess the physiological role of locally produced IGF-I, we have
      developed pancreatic-specific IGF-I gene deficiency (PID) by crossing Pdx1-Cre
      and IGF-I/loxP mice. PID mice are normal except for decreased blood glucose level
      and a 2.3-fold enlarged islet cell mass. When challenged with low doses of
      streptozotocin, control mice developed hyperglycemia after 6 days that was
      maintained at high levels for at least 2 months. In contrast, PID mice only
      exhibited marginal hyperglycemia after 12 days, maintained throughout the
      experiment. Fifteen days after streptozotocin, PID mice demonstrated
      significantly higher levels of insulin production. Furthermore, streptozotocin
      induced beta-cell apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL]
      assay) was significantly prevented in PID mice. Finally, PID mice exhibited a
      delayed onset of type 2 diabetes induced by a high-fat diet, accompanied by super
      enlarged pancreatic islets, increased insulin mRNA levels, and preserved
      sensitivity to insulin. Our results suggest that locally produced IGF-I within
      the pancreas inhibits islet cell growth; its deficiency provides a protective
      environment to the beta-cells and potential in combating diabetes.

PMID- 15561944
TI  - Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating
      Ca2+ signaling in beta-cells: implication in the glycemic control in rodents.
AB  - Ghrelin, isolated from the human and rat stomach, is the endogenous ligand for
      the growth hormone (GH) secretagogue receptor, which is expressed in a variety of
      tissues, including the pancreatic islets. It has been shown that low plasma
      ghrelin levels correlates with elevated fasting insulin levels and type 2
      diabetes. Here we show a physiological role of endogenous ghrelin in the
      regulation of insulin release and blood glucose in rodents. Acylated ghrelin, the
      active form of the peptide, was detected in the pancreatic islets. Counteraction
      of endogenous ghrelin by intraperitoneal injection of specific GH secretagogue
      receptor antagonists markedly lowered fasting glucose concentrations, attenuated
      plasma glucose elevation, and enhanced insulin responses during the glucose
      tolerance test (GTT). Conversely, intraperitoneal exogenous ghrelin GH
      independently elevated fasting glucose concentrations, enhanced plasma glucose
      elevation, and attenuated insulin responses during GTT. Neither GH secretagogue
      receptor antagonist nor ghrelin affected the profiles of the insulin tolerance
      test. In isolated islets, GH secretagogue receptor blockade and antiserum against
      acylated ghrelin markedly enhanced glucose-induced increases in insulin release
      and intracellular Ca2+ concentration ([Ca2+]i), whereas ghrelin at a relatively
      high concentration (10 nmol/l) suppressed insulin release. In single beta-cells,
      ghrelin attenuated glucose-induced first-phase and oscillatory [Ca2+]i increases
      via the GH secretagogue receptor and in a pertussis toxin-sensitive manner.
      Ghrelin also increased tetraethylammonium-sensitive delayed outward K+ currents
      in single beta-cells. These findings reveal that endogenous ghrelin in islets
      acts on beta-cells to restrict glucose-induced insulin release at least partly
      via attenuation of Ca2+ signaling, and that this insulinostatic action may be
      implicated in the upward control of blood glucose. This function of ghrelin,
      together with inducing GH release and feeding, suggests that ghrelin underlies
      the integrative regulation of energy homeostasis.

PMID- 15561945
TI  - Massive augmentation of stimulated insulin secretion induced by fatty acid-free
      BSA in rat pancreatic islets.
AB  - Incubation of rat pancreatic islets for 4-6 h with 100 micromol/l fatty acid-free
      BSA induced a 3- to 10-fold enhancement of insulin release to a subsequent
      challenge with 16.7 mmol/l glucose, without changing the typical biphasic pattern
      of the response. A similar enhancement was observed with other stimuli, such as
      leucine, depolarizing concentrations of KCl and tolbutamide, pointing to a
      general phenomenon and common mechanism for the augmentation. Norepinephrine
      completely blocked the stimulated response. The protein kinase C (PKC) inhibitor
      Ro 31-8220, which acts at the ATP-binding site and inhibits all PKC isoforms,
      strongly inhibited the enhancement of a subsequent glucose challenge when present
      during the BSA pretreatment period. In contrast, Go 6976, an inhibitor of
      conventional PKC isoforms, was without effect, even at the high concentration of
      1 micromol/l. Preincubation with calphostin C, which competes for the
      diacylglycerol (DAG)-binding site, therefore inhibiting conventional, novel, and
      PKC isoforms of the PKD type, completely abolished the enhancing effect of the
      BSA but did not affect secretion in islets treated with 10 micromol/l fatty acid
      free BSA. We conclude that the remarkable enhancement of insulin release is due
      to a change in glucose signaling and activation of a novel PKC isoform or a DAG
      binding protein.

PMID- 15561946
TI  - Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive
      K+ channels.
AB  - ATP-sensitive K+ channels (K(ATP) channels) control electrical activity in beta
      cells and therefore are key players in excitation-secretion coupling. Partial
      suppression of beta-cell K(ATP) channels in transgenic (AAA) mice causes
      hypersecretion of insulin and enhanced glucose tolerance, whereas complete
      suppression of these channels in Kir6.2 knockout (KO) mice leads to
      hyperexcitability, but mild glucose intolerance. To test the interplay of
      hyperexcitability and dietary stress, we subjected AAA and KO mice to a high-fat
      diet. After 3 months on the diet, both AAA and KO mice converted to an
      undersecreting and markedly glucose-intolerant phenotype. Although Kir6.2 is
      expressed in multiple tissues, its primary functional consequence in both AAA and
      KO mice is enhanced beta-cell electrical activity. The results of our study
      provide evidence that, when combined with dietary stress, this hyperexcitability
      is a causal diabetic factor. We propose an "inverse U" model for the response to
      enhanced beta-cell excitability: the expected initial hypersecretion can progress
      to undersecretion and glucose-intolerance, either spontaneously or in response to
      dietary stress.

PMID- 15561947
TI  - High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic
      cells into functional insulin-producing cells.
AB  - Pdx1 has been shown to convert hepatocytes into both exocrine and endocrine
      pancreatic cells in mice, but it fails to selectively convert hepatocytes into
      pure insulin-producing cells (IPCs). The molecular mechanisms underlying the
      transdifferentiation remain unclear. In this study, we generated a stably
      transfected rat hepatic cell line named WB-1 that expresses an active form of
      Pdx1 along with a reporter gene, RIP-eGFP. Our results demonstrate that Pdx1
      induces the expression of multiple genes related to endocrine pancreas
      development and islet function in these liver cells. We do not however find any
      expression of the late-stage genes (Pax4, Pax6, Isl-1, and MafA) related to beta
      cell development, and the cells do not secrete insulin upon the glucose
      challenge. Yet when WB-1 cells are transplanted into diabetic NOD-scid mice,
      these genes become activated and hyperglycemia is completely reversed. Detailed
      comparison of gene expression profiles between pre- and posttransplanted WB-1
      cells demonstrates that the WB-1 cells have similar properties as that seen in
      pancreatic beta-cells. In addition, in vitro culture in high-glucose medium is
      sufficient to induce complete maturation of WB-1 cells into functional IPCs. In
      summary, we find that Pdx1-VP16 is able to selectively convert hepatic cells into
      pancreatic endocrine precursor cells. However, complete transdifferentiation into
      functional IPCs requires additional external factors, including high glucose or
      hyperglycemia. Thus, transdifferentiation of hepatocytes into functional IPCs may
      serve as a viable therapeutic option for patients with type 1 diabetes.

PMID- 15561948
TI  - Stimulation of insulin release by glucose is associated with an increase in the
      number of docked granules in the beta-cells of rat pancreatic islets.
AB  - Electron microscopy and quantitative stereological techniques were used to study
      the dynamics of the docked granule pool in the rat pancreatic beta-cell. The mean
      number of granules per beta-cell was 11,136. After equilibration in RPMI
      containing 5.6 mmol/l glucose, 6.4% of the granules (approximately 700) were
      docked at the plasma membrane (also measured as [means +/- SE] 4.3 +/- 0.6 docked
      granules per 10 microm of plasma membrane at the perimeter of the cell sections).
      After a 40-min exposure to 16.7 mmol/l glucose, 10.2% of the granules
      (approximately 1,060) were docked (6.4 +/- 0.8 granules per 10 microm of plasma
      membrane). Thus, the docked pool increased by 50% during stimulation with
      glucose. Islets were also exposed to 16.7 mmol/l glucose in the absence or
      presence of 10 micromol/l nitrendipine. In the absence and presence of
      nitrendipine, there were 6.1 +/- 0.7 and 6.3 +/- 0.6 granules per 10 microm of
      membrane, respectively. Thus, glucose increased granule docking independently of
      increased [Ca2+]i and exocytosis. The data suggest a limit to the number of
      docking sites. As the rate of docking exceeded the rate of exocytosis, docking is
      not rate limiting for insulin release. Only with extremely high release rates,
      glucose stimulation after a 4-h incubation with a high concentration of fatty
      acid-free BSA, was the docked granule pool reduced in size.

PMID- 15561949
TI  - Insulin stimulates and diabetes inhibits O-linked N-acetylglucosamine transferase
      and O-glycosylation of Sp1.
AB  - Insulin stimulates both the biosynthesis of transcription factor Sp1 and its O
      linked N-acetylglucosaminylation (O-GlcNAcylation), which promotes nuclear
      localization of Sp1 and its ability to transactivate calmodulin (CaM) gene
      transcription. To investigate this further, we incubated H-411E liver cells with
      insulin (10,000 microU/ml) and quantified the subcellular distribution of O
      GlcNAc transferase (OGT) and O-GlcNAc-modified Sp1. We also examined the
      phosphorylation of Sp1 using both Western blot and incorporation of 32P into Sp1.
      The results demonstrate that insulin, but not glucagon, stimulates OGT synthesis
      and enhances cytosolic staining of OGT (histochemical). Insulin increases O
      GlcNAc-Sp1, which peaks at 30 min, followed by decline at 4 h. In contrast,
      insulin initiates phosphorylation of Sp1 early, followed by a continued increase
      in phosphorylated Sp1 (PO4-Sp1) at 4 h. A reciprocal relationship between O
      GlcNAc-Sp1 and PO4-Sp1 was observed. To explore the pathophysiological relevance,
      we localized OGT in liver sections from streptozotocin (STZ)-induced diabetic
      rats. We observed that staining of OGT in STZ-induced diabetic rat liver is
      clearly diminished, but it was substantially restored after 6 days of insulin
      treatment. We conclude that insulin stimulates CaM gene transcription via a
      dynamic interplay between O-glycosylation and phosphorylation of Sp1 that
      modulates stability, mobility, subcellular compartmentalization, and activity.

PMID- 15561950
TI  - Phenotypic characteristics of GAD antibody-positive recently diagnosed patients
      with type 2 diabetes in North America and Europe.
AB  - A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes
      Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in
      recently diagnosed drug-naive patients with type 2 diabetes that allows for the
      evaluation of GAD positivity in the context of anthropometric and biochemical
      characteristics. Of the 4,134 subjects enrolled in ADOPT for whom GAD status was
      obtained, 174 (4.2%) were GAD positive, with the prevalence of GAD antibodies
      being similar in North America (4.7%) and Europe (3.7%). Although BMI and age
      were similar, GAD-positive patients had a lower fasting insulin level, compatible
      with them being more insulin sensitive. The lower fasting insulin concentration
      was accompanied by a decreased early insulin response to oral glucose. However,
      when this insulin response was corrected for the degree of insulin sensitivity,
      GAD-positive and -negative patients had similar beta-cell function. Consistent
      with the difference in insulin sensitivity, GAD-positive patients had higher HDL
      cholesterol and lower triglyceride levels. In the GAD-positive individuals, the
      prevalence of the metabolic syndrome as defined by NCEP ATP III (National
      Cholesterol Education Program Adult Treatment Panel III) was also lower (74.1 vs.
      83.7%, P = 0.0009). These phenotypic differences may underlie a potential
      difference in the natural history of hyperglycemia and its clinical outcomes.

PMID- 15561951
TI  - Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db
      mouse heart.
AB  - Although it is known that insulin-dependent (type 1) diabetes results in
      depressed contractile performance associated with diminished sarcoendoplasmic
      reticular Ca2+-ATPase (SERCA2a) activity, findings in insulin-resistant (type 2)
      diabetes suggest a less clear association. The db/db insulin-resistant mouse
      model exhibits decreased cardiac performance both in situ and in isolated ex vivo
      working hearts. In this study, contractile performance and calcium transients
      were measured in Langendorff-perfused hearts and isolated cardiac myocytes.
      Diabetic (db/db) mouse hearts demonstrated decreased rates of contraction,
      relaxation, and pressure development. Calcium transients from isolated myocytes
      revealed significantly lower diastolic and systolic levels of calcium in diabetic
      hearts. Furthermore, the decay rate of the calcium transient was significantly
      reduced in diabetic myocytes, suggesting a diminished capacity for cytosolic
      calcium removal not associated with a change in sodium-calcium exchanger
      activity. Calcium leakage from the sarcoplasmic reticulum (SR) measured using
      tetracaine was significantly increased in diabetic myocytes. Western blot
      analysis indicated only a small decrease in SERCA2a expression in diabetic mice,
      but a large increase in phospholamban expression. Expression of the ryanodine
      receptor did not differ between groups. In conclusion, the decreased contractile
      function observed in the db/db diabetic mouse model appears to be related to
      decreased calcium handling by the SR.

PMID- 15561952
TI  - Palmitate-induced interleukin-6 expression in human coronary artery endothelial
      cells.
AB  - Obesity-linked insulin resistance is associated with chronic inflammation and
      cardiovascular complications. Free fatty acids (FFAs) are prominent candidates
      for the molecular link between these disorders. In this study, we determined
      whether FFAs contribute to vascular inflammation via induction of interleukin
      (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth
      muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our
      findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6
      receptor mRNA expression was very low in these cells. Palmitate, but not
      linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P <
      0.001) and, to a less relevant extent, in CASMCs (P < 0.01). gp130 remained
      unaffected. As to potency, palmitate was comparable with the IL-6-inducer IL
      1beta. To substantiate our in vitro data, we examined the plasma FFA pattern in
      54 healthy human subjects and studied the relation of individual FFAs with plasma
      IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs,
      even after adjusting for body fat (r = 0.33, P < 0.05) and total FFAs (r = 0.29,
      P < 0.05). We show here that the common plasma FFA palmitate induces high levels
      of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This
      points to a potential contribution of palmitate to vascular inflammation.

PMID- 15561953
TI  - Hyperlipidemia in concert with hyperglycemia stimulates the proliferation of
      macrophages in atherosclerotic lesions: potential role of glucose-oxidized LDL.
AB  - Hyperglycemia and hyperlipidemia are important risk factors for diabetes
      accelerated atherosclerosis. Macrophage proliferation has been implicated in the
      progression of atherosclerosis. We therefore investigated the effects of
      hyperglycemia and hyperlipidemia on macrophage proliferation in murine
      atherosclerotic lesions and isolated primary macrophages. Hyperglycemic LDL
      receptor-deficient mice that were fed a cholesterol-free diet for 12 weeks did
      not have elevated cholesterol levels compared with nondiabetic mice, and there
      was no evidence of increased macrophage proliferation in atherosclerotic lesions.
      Moreover, elevated glucose levels did not increase proliferation of isolated
      mouse peritoneal macrophages. In contrast, hyperglycemic LDL receptor-deficient
      mice that were fed a cholesterol-rich diet showed increased cholesterol levels
      concomitant with macrophage proliferation in atherosclerotic lesions. Glucose
      promoted lipid and protein oxidation of LDL in vitro. Glucose-oxidized LDL
      resulted in phosphorylation of extracellular signal-regulated kinase and protein
      kinase B/Akt and stimulated proliferation of isolated macrophages. The mitogenic
      effect of glucose-oxidized LDL was mediated by CD36 and by extracellular signal
      regulated kinase activation induced by protein kinase C-dependent and
      phosphatidylinositol 3-kinase-dependent pathways. Thus, hyperglycemia is not
      sufficient to stimulate macrophage proliferation in lesions of atherosclerosis or
      in isolated macrophages. A combination of hyperglycemia and hyperlipidemia,
      however, stimulates macrophage proliferation by a pathway that may involve the
      glucose-dependent oxidation of LDL.

PMID- 15561954
TI  - Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and
      function.
AB  - Hyperglycemia and hypoxia are suggested to play essential pathophysiological
      roles in the complications of diabetes, which may result from a defective
      response of the tissues to low oxygen tension. In this study, we show that in
      primary dermal fibroblasts and endothelial cells, hyperglycemia interferes with
      the function of hypoxia-inducible factor-1 (HIF-1), a transcription factor that
      is essential for adaptive responses of the cell to hypoxia. Experiments using
      proteasomal and prolyl hydroxylases inhibitors indicate that hyperglycemia
      inhibits hypoxia-induced stabilization of HIF-1alpha protein levels against
      degradation and suggest that mechanisms in addition to proline hydroxylation may
      be involved. This effect of hyperglycemia was dose dependent and correlates with
      a lower transcription activation potency of HIF-1alpha, as assessed by transient
      hypoxia-inducible reporter gene assay. Regulation of HIF-1alpha function by
      hyperglycemia could be mimicked by mannitol, suggesting hyperosmolarity as one
      critical parameter. The interference of hyperglycemia with hypoxia-dependent
      stabilization of HIF-1alpha protein levels was confirmed in vivo, where only very
      low levels of HIF-1alpha protein could be detected in diabetic wounds, as
      compared with chronic venous ulcers. In conclusion, our data demonstrate that
      hyperglycemia impairs hypoxia-dependent protection of HIF-1alpha against
      proteasomal degradation and suggest a mechanism by which diabetes interferes with
      cellular responses to hypoxia.

PMID- 15561955
TI  - Effect of long-term administration of alpha-lipoic acid on retinal capillary cell
      death and the development of retinopathy in diabetic rats.
AB  - Oxidative stress is increased in the retina in diabetes, and it is considered to
      play an important role in the development of retinopathy. alpha-Lipoic acid, a
      thiol antioxidant, has been shown to have beneficial effects on polyneuropathy
      and on the parameters of oxidative stress in various tissues, including nerve,
      kidney, and retina. The purpose of this study was to examine the effect of alpha
      lipoic acid on retinal capillary cell apoptosis and the development of pathology
      in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving
      diets supplemented with or without alpha-lipoic acid (400 mg/kg) for 11 months of
      diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick
      end labeling) and formation of acellular capillaries were investigated in the
      trypsin-digested retinal microvessels. The effect of alpha-lipoic acid
      administration on retinal 8-hydroxy-2'deoxyguanosine (8-OHdG) and nitrotyrosine
      levels was determined by enzyme-linked immunosorbent assay. alpha-Lipoic acid
      administration for the entire duration of diabetes inhibited capillary cell
      apoptosis and the number of acellular capillaries in the retina, despite similar
      severity of hyperglycemia in the two diabetic groups (with and without alpha
      lipoic acid). Retinal 8-OHdG and nitrotyrosine levels were increased by over
      twofold and 70%, respectively, in diabetes, and alpha-lipoic acid administration
      inhibited these increases. Our results demonstrate that the long-term
      administration of alpha-lipoic acid has beneficial effects on the development of
      diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA
      and nitrotyrosine in the retina. alpha-Lipoic acid supplementation represents an
      achievable adjunct therapy to help prevent vision loss in diabetic patients.

PMID- 15561956
TI  - Effects of polyol pathway hyperactivity on protein kinase C activity, nociceptive
      peptide expression, and neuronal structure in dorsal root ganglia in diabetic
      mice.
AB  - We explored the specific impact of polyol pathway hyperactivity on dorsal root
      ganglia (DRG) using transgenic mice that overexpress human aldose reductase
      because DRG changes are crucial for the development of diabetic sensory
      neuropathy. Littermate mice served as controls. Half of the animals were made
      diabetic by streptozotocin injection and followed for 12 weeks. After diabetes
      onset, diabetic transgenic mice showed a significant elevation of pain sensation
      threshold after transient decrease and marked slowing of motor and sensory nerve
      conduction at the end of the study, while these changes were modest in diabetic
      littermate mice. Protein kinase C (PKC) activities were markedly reduced in
      diabetic transgenic mice, and the changes were associated with reduced expression
      of membrane PKC-alpha isoform that was translocated to cytosol. Membrane PKC
      betaII isoform expression was contrariwise increased. Calcitonin gene-related
      peptide-and substance P-positive neurons were reduced in diabetic transgenic mice
      and less severely so in diabetic littermate mice. Morphometric analysis disclosed
      neuronal atrophy only in diabetic transgenic mice. Treatment with an aldose
      reductase inhibitor (fidarestat 4 mg x kg(-1) x day(-1), orally) corrected all of
      the changes detected in diabetic transgenic mice. These findings underscore the
      pathogenic role of aldose reductase in diabetic sensory neuropathy through the
      altered cellular signaling and peptide expressions in DRG neurons.

PMID- 15561957
TI  - Development of late-stage diabetic nephropathy in OVE26 diabetic mice.
AB  - OVE26 mice are a transgenic model of severe early-onset type 1 diabetes. These
      mice develop diabetes within the first weeks of life and can survive well over a
      year with no insulin treatment, and they maintain near normal body weight. To
      determine whether OVE26 mice provide a valuable model of chronic diabetic
      nephropathy (DN), OVE26 diabetic mice were compared with their nondiabetic
      littermates for functional and structural characteristics of DN. OVE26 mice
      exhibited pronounced polyuria and significant albuminuria by 2 months of age (305
      microg/24 h in OVE26 vs. 20 microg/24 h in controls). Albumin excretion rate
      increased progressively with age and exceeded 15,000 microg/24 h at 9 months of
      age. The profound loss of albumin led to hypoalbuminemia in some diabetic
      animals. Albuminuria coincided with an elevation in blood pressure as measured by
      tail cuff. The glomerular filtration rate (GFR) in OVE26 mice measured using
      fluorescein isothiocynate inulin clearance demonstrated that GFR increased
      significantly from 2 to 3 months of age and then decreased significantly from 5
      to 9 months. GFR in 9-month-old diabetic mice was significantly lower than that
      of 9-month-old control mice. The decline in GFR coincided with a significant
      increase in renal vascular resistance. Structural studies showed an almost
      twofold increase in kidney weight between 2 and 5 months. Diabetic mice also
      showed progressively enlarged glomeruli and expanded mesangium with diffuse and
      nodular expansion of mesangial matrix. Tubulointerstitial fibrosis was also
      observed in these mice. Glomerular basement membrane was thickened in OVE26 mice.
      In summary, OVE26 mice demonstrate that most of the characteristics of human DN
      can be produced by chronic hyperglycemia in a murine model. This model will be
      useful for improved understanding and treatment of DN.

PMID- 15561958
TI  - Metformin prevents the development of acute lipid-induced insulin resistance in
      the rat through altered hepatic signaling mechanisms.
AB  - Metformin reduces the incidence of progression to type 2 diabetes in humans with
      obesity or impaired glucose tolerance. We used an animal model to investigate
      whether metformin could prevent acute lipid-induced insulin resistance and the
      mechanisms involved. Metformin or vehicle was administered to rats daily for 1
      week. Rats were studied basally, after 3.75 h of intralipid-heparin or glycerol
      infusion, or after 5 h of infusion with a hyperinsulinemic-euglycemic clamp
      between 3 and 5 h. Metformin had no effect on plasma triacylglycerol or
      nonesterified fatty acid concentrations and did not alter glucose turnover or
      gluconeogenic enzyme mRNA after lipid infusion. However, metformin normalized
      hepatic glucose output and increased liver glycogen during lipid infusion and
      clamp. Basal liver (but not muscle or fat) AMP-activated protein kinase activity
      was increased by metformin (by 310%; P < 0.01), associated with increased
      phosphorylation of acetyl CoA carboxylase. Postclamp liver but not muscle
      phosphorylated/total Akt protein was increased, whereas basal c-Jun NH2-terminal
      kinase-1 and -2 protein expression were reduced (by 39 and 53%, respectively; P <
      0.05). Metformin also increased hepatic basal IkappaBalpha levels (by 260%; P <
      0.001) but had no effect on tyrosine phosphorylation or expression of insulin
      receptor substrate-1 (IRS-1). In summary, metformin opposes the development of
      acute lipid-induced insulin resistance in the liver through alterations in
      multiple signaling pathways.

PMID- 15561959
TI  - A novel glucagon receptor antagonist inhibits glucagon-mediated biological
      effects.
AB  - Glucagon maintains glucose homeostasis during the fasting state by promoting
      hepatic gluconeogenesis and glycogenolysis. Hyperglucagonemia and/or an elevated
      glucagon-to-insulin ratio have been reported in diabetic patients and animals.
      Antagonizing the glucagon receptor is expected to result in reduced hepatic
      glucose overproduction, leading to overall glycemic control. Here we report the
      discovery and characterization of compound 1 (Cpd 1), a compound that inhibits
      binding of 125I-labeled glucagon to the human glucagon receptor with a half
      maximal inhibitory concentration value of 181 +/- 10 nmol/l. In CHO cells
      overexpressing the human glucagon receptor, Cpd 1 increased the half-maximal
      effect for glucagon stimulation of adenylyl cyclase with a KDB of 81 +/- 11
      nmol/l. In addition, Cpd 1 blocked glucagon-mediated glycogenolysis in primary
      human hepatocytes. In contrast, a structurally related analog (Cpd 2) was not
      effective in blocking glucagon-mediated biological effects. Real-time measurement
      of glycogen synthesis and breakdown in perfused mouse liver showed that Cpd 1 is
      capable of blocking glucagon-induced glycogenolysis in a dosage-dependent manner.
      Finally, when dosed in humanized mice, Cpd 1 blocked the rise of glucose levels
      observed after intraperitoneal administration of exogenous glucagon. Taken
      together, these data suggest that Cpd 1 is a potent glucagon receptor antagonist
      that has the capability to block the effects of glucagon in vivo.

PMID- 15561960
TI  - Genetic determinants of energy expenditure and insulin resistance in diet-induced
      obesity in mice.
AB  - Diet-induced obesity is the primary determinant of the current epidemic of
      diabetes. We have explored the role of genetics in this phenomenon, using C57Bl/6
      (B6), 129S6/SvEvTac (129), and intercross (B6 x 129)F2 mice on a low- or high-fat
      diet. Over an 18-week period, B6 and F2 mice gained more weight, had higher
      levels of insulin and leptin, and showed greater glucose intolerance than 129
      mice, despite lower food intake. By contrast, metabolic rate and diet-induced
      thermogenesis were significantly higher in the 129 mice. Genome-wide scans
      identified several quantitative trait loci, including a quantitative trait locus
      that was linked with hyperinsulinemia/insulin resistance on chromosome 14 in a
      region similar to that seen in mice with genetically induced insulin resistance.
      Microarray analysis indicated significant changes in expression levels between B6
      and 129 mice in the identified chromosomal area of Wnt5a and protein kinase
      Cdelta (PKCdelta). Thus, caloric efficiency, i.e., the "thrifty gene," is a
      dominant-acting genetic determinant of diet-induced obesity in mice and can be
      linked to a locus on chromosome 14, including genes linked to adipose development
      and insulin sensitivity.

PMID- 15561961
TI  - Heterogeneity in the magnitude of the insulin gene effect on HLA risk in type 1
      diabetes.
AB  - There is still uncertainty concerning the joint action of the two established
      type 1 diabetes susceptibility loci, the HLA class II DQB1 and DRB1 genes (IDDM1)
      and the insulin gene (INS) promoter (IDDM2). Some previous studies reported
      independence, whereas others suggested heterogeneity in the relative effects of
      the genotypes at these disease loci. In this study, we have assessed the combined
      effects of the HLA-DQB1/DRB1 and INS genotypes in 944 type 1 diabetic patients
      and 1,023 control subjects, all from Sardinia. Genotype variation at INS
      significantly influenced disease susceptibility in all HLA genotype risk
      categories. However, there was a significant heterogeneity (P = 2.4 x 10(-4)) in
      the distribution of the INS genotypes in patients with different HLA genotypes.
      The INS predisposing genotype was less frequent (74.9%) in high-risk HLA genotype
      positive patients than in those with HLA intermediate-risk (86.1%) and low-risk
      (84.8%) categories. Gene-gene interaction modeling led to rejection of the
      additive model, whereas a multiplicative model showed a better, albeit still
      partial, fit to the observed data. These genetic results are consistent with an
      interaction between the protein products of the HLA and INS alleles, in which
      both the affinity of the various HLA class II molecules for a preproinsulin
      derived peptide and the levels of this peptide in the thymus act jointly as key
      regulators of type 1 diabetes autoimmunity.

PMID- 15561962
TI  - Polymorphism in the calsequestrin 1 (CASQ1) gene on chromosome 1q21 is associated
      with type 2 diabetes in the old order Amish.
AB  - Calsequestrin (CASQ)1 is involved in intracellular storage and release of
      calcium, a process that has been shown to mediate glucose transport in muscle.
      Its gene, CASQ1, is encoded on chromosome 1q21, a region that has been linked to
      type 2 diabetes in the Amish and several other populations. We screened all 11
      exons, exon-intron junctions, and the proximal regulatory region of CASQ1 for
      mutations. We detected four novel single nucleotide polymorphisms (SNPs) (-1470C-
      >T, -1456delG, -1366insG, and 593C-->T). Ten informative SNPs within CASQ1 were
      genotyped in Amish subjects with type 2 diabetes (n = 145), impaired glucose
      tolerance (n = 148), and normal glucose tolerance (n = 358). Rs2275703 and
      rs617698 in introns 4 and 2 were significantly associated with type 2 diabetes (P
      = 0.008 and 0.04, respectively); three other SNPs showed borderline evidence for
      association to type 2 diabetes (P = 0.076-0.093). Furthermore, in nondiabetic
      subjects (n = 754), both rs2275703 and rs617698 were significantly associated
      with glucose area under the curve during an oral glucose tolerance test (P =
      0.035 and 0.013, respectively). Haplotype analysis suggested that no haplotype
      could explain these associations better than rs2275703. These findings, coupled
      with similar findings in Utah Caucasians, suggest that sequence variation in
      CASQ1 may influence risk of type 2 diabetes.

PMID- 15561963
TI  - Calsquestrin 1 (CASQ1) gene polymorphisms under chromosome 1q21 linkage peak are
      associated with type 2 diabetes in Northern European Caucasians.
AB  - Genome-wide scans in multiple populations have identified chromosome 1q21-q24 as
      one susceptibility region for type 2 diabetes. To map the susceptibility genes,
      we first placed a dense single nucleotide polymorphism (SNP) map across the
      linked region. We identified two SNPs that showed strong associations, and both
      mapped to within intron 2 of the calsequestrin 1 (CASQ1) gene. We tested the
      hypothesis that sequence variation in or near CASQ1 contributed to type 2
      diabetes susceptibility in Northern European Caucasians by identifying additional
      SNPs from the public database and by screening the CASQ1 gene for additional
      variation. In addition to 15 known SNPs in this region, we found 8 new SNPs, 3 of
      which were in exons. A single rare nonsynonymous SNP in exon 11 (A348V) was not
      associated with type 2 diabetes. The associated SNPs were localized to the region
      between -1,404 in the 5' flanking region and 2,949 in intron 2 (P = 0.002 to P =
      0.034). No SNP 3' to intron 2, including the adjacent gene PEA15, showed an
      association. The strongest associations were restricted to individuals of
      Northern European ancestry ascertained in Utah. A six-marker haplotype was also
      associated with type 2 diabetes (P = 0.008), but neither transmission
      disequilibrium test nor family-based association studies were significant for the
      most strongly associated SNP in intron 2 (SNP CASQ2312). An independent
      association of SNPs in introns 2 and 4 with type 2 diabetes is reported in Amish
      families with linkage to chromosome 1q21-q24. Our findings suggest that noncoding
      SNPs in CASQ1 alter diabetes susceptibility, either by a direct effect on CASQ1
      gene expression or perhaps by regulating a nearby gene such as PEA15.

PMID- 15561964
TI  - Linkage analysis of diabetes status among hypertensive families: the Hypertension
      Genetic Epidemiology Network study.
AB  - Type 2 diabetes susceptibility is determined by multiple genetic and
      environmental factors. Genome-wide linkage scans have localized common regions,
      possibly harboring susceptibility genes on chromosomes 1, 2, 12, and 20.
      Variability in linkage findings underscores the probable genetic heterogeneity of
      type 2 diabetes. Thus, we conducted a genome scan of diabetes status using
      maximum likelihood methods that model affection status by a liability threshold
      model. Hypertensive sibships and their offspring and/or parents in the
      Hypertension Genetic Epidemiology Network study were recruited from five field
      centers. The diabetes phenotype was derived using the World Health Organization
      criteria and adjusted for race/study center, age, age2, sex, and with and without
      percent body fat. In total, 567 diabetic participants were identified in 437
      families. Variance component linkage analysis was performed among 1,545
      Caucasians and 1,608 African Americans using race-specific marker allele
      frequencies. We detected a quantitative trait loci (QTLs) influencing diabetes
      variance (logarithm of odds = 3.4) on chromosome 22, which overlaps a positive
      type 2 diabetes finding among Canadian Oji-Cree Indians. We also observed
      suggestive evidence for linkage on chromosomes 1, 2, 5, 8, 14, 17, and 19. The
      identification and replication of type 2 diabetes QTLs will bring us closer to
      the detection of functional genes that influence diabetes susceptibility.

PMID- 15561965
TI  - Association testing in 9,000 people fails to confirm the association of the
      insulin receptor substrate-1 G972R polymorphism with type 2 diabetes.
AB  - The insulin receptor substrate (IRS)-1 is an important component of the insulin
      signal transduction cascade. Several reports suggest that a Gly-->Arg change in
      codon 972 is associated with type 2 diabetes and related traits, and a recent
      meta-analysis reported a modest but nominally significant association with type 2
      diabetes (odds ratio [OR] 1.25 in favor of carriers of the Arg allele [95% CI
      1.05-1.48). To test the reproducibility of the model in a recent meta-analysis,
      we examined genotype-phenotype correlation in three large Caucasian samples (not
      previously reported for this variant) totaling 9,000 individuals (estimated to
      have >95% power to obtain a P < 0.05 for the OR of 1.25 estimated in the meta
      analysis). In our combined sample, comprising 4,279 case and 3,532 control
      subjects, as well as 1,189 siblings discordant for type 2 diabetes, G972R was not
      associated with type 2 diabetes (OR 0.96 [0.84-1.10], P = 0.60). Genotype at
      G972R had no significant effect on various measures of insulin secretion or
      insulin resistance in a set of Scandinavian samples in whom we had detailed
      phenotypic data. In contrast, the well-documented associations of peroxisome
      proliferator-activated receptor gamma P12A and Kir6.2 E23K with type 2 diabetes
      are both robustly observed in these 9,000 subjects, including an additional
      (previously unpublished) confirmation of Kir6.2 E23K and type 2 diabetes in the
      Polish and North American samples (combined OR 1.15 [1.05-1.26], P = 0.001).
      Despite genotyping 9,000 people and >95% power to reproduce the estimated OR from
      the recent meta-analysis, we were unable to replicate the association of the IRS
      1 G972R polymorphism with type 2 diabetes.

PMID- 15561966
TI  - Association studies of insulin receptor substrate 1 gene (IRS1) variants in type
      2 diabetes samples enriched for family history and early age of onset.
AB  - The gene encoding insulin receptor substrate-1 (IRS1) represents a strong
      biological candidate for a contributory role in type 2 diabetes susceptibility.
      Indeed, functional studies have implicated the G971R variant, and a recent meta
      analysis of 27 association studies suggested that carriage of 971R was associated
      with a 25% increase in disease risk. However, this association has not been
      evaluated in large samples. The present study genotyped the P512A and G971R IRS1
      variants in 971 U.K. type 2 diabetic subjects ascertained for strong family
      history and/or early onset, as well as 1,257 control subjects matched by
      ethnicity. There was no evidence for association with type 2 diabetes for either
      variant. (For example, the odds ratio [OR] for carriage of 971R was 1.11 [95% CI
      0.86-1.44, P = 0.44]) An updated meta-analysis (31 studies: 5,104 case and 7,418
      control subjects) remained significant for the G971R association (P = 0.025),
      albeit with a diminished OR (1.15 [95% CI 1.02-1.31]). Additional studies of IRS1
      variation will be required to obtain a robust estimate of the overall
      contribution of IRS1 variation to type 2 diabetes susceptibility, but the current
      study suggests that previous studies have overestimated the magnitude of this
      effect.

PMID- 15561967
TI  - Mapping non-class II H2-linked loci for type 1 diabetes in nonobese diabetic
      mice.
AB  - Major histocompatibility complex (MHC) plays a largely predominant role in the
      genetic predisposition to type 1 diabetes, in both humans and rodents. While
      class II loci have long been recognized as essential, they do not fully explain
      the MHC-linked genetic component of type 1 diabetes. In the present study, using
      new NOD congenic strains harboring defined chromosomal segments from C57BL/6
      mice, we circumscribed three distinct loci influencing murine type 1 diabetes and
      tightly linked to but separated from the class II region. Our findings might
      guide the search for additional HLA-linked loci in human type 1 diabetes.

PMID- 15561968
TI  - Quantitative trait loci for obesity- and diabetes-related traits and their
      dietary responses to high-fat feeding in LGXSM recombinant inbred mouse strains.
AB  - Genetic variation in response to high-fat diets is important in understanding the
      recent secular trends that have led to increases in obesity and type 2 diabetes.
      The examination of quantitative trait loci (QTLs) for both obesity- and diabetes
      related traits and their responses to a high-fat diet can be effectively
      addressed in mouse model systems, including LGXSM recombinant inbred (RI) mouse
      strains. A wide range of obesity- and diabetes-related traits were measured in
      animals from 16 RI strains with 8 animals of each sex fed a high- or low-fat diet
      from each strain. Marker associations were measured at 506 microsatellite markers
      spread throughout the mouse genome using a nested ANOVA. Locations with
      significant effects on the traits themselves and/or trait dietary responses were
      identified after correction for multiple comparisons by limiting the false
      detection rate. Nonsyntenic associations of marker genotypes were common at QTL
      locations so that the significant results were limited to loci still significant
      in multiple QTL models. We discovered 91 QTLs at 39 locations. Many of these
      locations (n = 31) also showed genetic effects on dietary response, typically
      because the loci produced significantly larger effects on the high-fat diet. Fat
      depot weights, leptin levels, and body weight at necropsy tended to map to the
      same locations and were responsible for a majority of the dietary response QTLs.
      Basal glucose levels and the response to glucose challenge mapped together in
      locations distinct from those affecting obesity. These QTL locations form a panel
      for further research and fine mapping of loci affecting obesity- and diabetes
      related traits and their responses to high-fat feeding.

PMID- 15561969
TI  - Polymorphisms in both promoters of hepatocyte nuclear factor 4-alpha are
      associated with type 2 diabetes in the Amish.
AB  - Hepatocyte nuclear factor 4-alpha (HNF4A) is a transcription factor located on
      chromosome 20q13 that regulates expression of genes involved in glucose
      metabolism and homeostasis. Recently, two groups independently identified single
      nucleotide polymorphism (SNPs) in an alternate upstream promoter (P2) of HNF4A
      that were associated with type 2 diabetes in Ashkenazi Jews and Finns. We
      genotyped haplotype-tagging SNPs (htSNPs) across the two promoter regions and the
      coding region of HNF4A in individuals with type 2 diabetes (n = 137), impaired
      glucose tolerance (IGT) (n = 139), and normal glucose tolerance (n = 342) from
      the Amish Family Diabetes Study (AFDS) to test for association with type 2
      diabetes. In the P1 promoter region, we observed a significant association
      between the A allele of rs2425640 and type 2 diabetes (odds ratio [OR] 1.60, P =
      0.03). Furthermore, the mean age of type 2 diabetes onset was, on average, 5.1
      years earlier in those with the AA or GA genotype at SNP rs2425640 than in those
      with the GG genotype (57.8 vs. 62.9 years, P = 0.011). In the P2 promoter, the
      htSNP rs1884614 showed borderline association with both type 2 diabetes (OR 1.40,
      P = 0.09) and the combined type 2 diabetes/IGT trait (1.35, P = 0.07). In an
      expanded set of 698 nondiabetic AFDS subjects, we found association between
      rs1884614 and glucose area under the curve during an oral glucose tolerance test
      (additive model, P = 0.022; dominant model, P = 0.010). The results of this study
      provide evidence that variants in both the P1 and P2 promoters of HNF4A increase
      risk for typical type 2 diabetes.

PMID- 15561970
TI  - Variation in the interleukin-6 receptor gene associates with type 2 diabetes in
      Danish whites.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of
      various human diseases such as type 2 diabetes and obesity. IL-6 signals via a
      heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6
      receptor [IL6R]) and a signal transducing subunit (gp130). The IL6R gene maps to
      an important candidate locus for type 2 diabetes on chromosome 1q21. An Asp358Ala
      polymorphism of the IL6R has been reported to associate with obesity in Pima
      Indians. We investigated the Asp358Ala polymorphism in relation to type 2
      diabetes, obesity, and other pre-diabetic quantitative traits among Danish
      whites. By applying a recessive genetic model in a case-control study of 1,349
      type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a
      significant difference in genotype distribution (P = 0.008) and in allele
      frequency (Ala-allele 38.3% [95% CI 36.5-40.1] in diabetic subjects vs. 41.2%
      [40.2-42.2] in control subjects; P = 0.007). The odds ratio for the Asp/Asp
      carriers versus Ala/Ala carriers was 1.38 (1.09-1.71). Among 4,251 middle-aged
      glucose-tolerant subjects, the Asp358Ala polymorphism was not associated with
      estimates of obesity, post-oral glucose tolerance test serum insulin release, or
      the homeostasis model assessment of insulin resistance index. In conclusion, the
      Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish
      whites.

PMID- 15561971
TI  - Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue
      protection: role of macrophages.
AB  - The role of monocytes/macrophages in the pathogenesis of ischemia-reperfusion
      injury (IRI) is unknown. We sought to determine whether activation of macrophage
      adenosine 2A (A(2A)) receptors (A(2A)Rs) mediates tissue protection. We subjected
      C57Bl/6 mice infused with clodronate [dichloromethylene bisphosphonate
      (Cl(2)MBP)] to IRI (32 min of ischemia followed by 24 h of reperfusion) to
      deplete them of macrophages. IRI induced an elevation of plasma creatinine that
      was reduced with Cl(2)MBP (26% of control). Adoptive transfer of murine RAW 264.7
      cells reconstituted injury, an effect blocked significantly by A(2A) agonists
      (27% of plasma creatinine from mice reconstituted with macrophages). Macrophages
      subjected to A(2A) knockout by small interfering RNA were adoptively transferred
      to macrophage-depleted mice and reconstituted injury (110% of control mice);
      however, the increase in plasma creatinine was blocked by A(2A) agonists (20% of
      vehicle treatment). Finally, the A(2A) agonist effect on IRI was blocked in
      macrophage-depleted A(2A)-knockout mice reconstituted with wild-type RAW 264.7
      cells. RNase protection assays 24 h after IRI demonstrated that macrophages are
      required for IL-6 and TGF-beta mRNA induction. However, A(2A) agonist-mediated
      tissue protection is independent of IL-6 and TGF-beta mRNA. We conclude that the
      full extent of IRI requires macrophages and that A(2A) agonist-mediated tissue
      protection is independent of activation of macrophage A(2A)Rs.

PMID- 15561972
TI  - Biotin uptake by human proximal tubular epithelial cells: cellular and molecular
      aspects.
AB  - Cellular and molecular regulation of renal biotin uptake in humans is not well
      defined. The contribution of the human Na(+)-dependent multivitamin transporter
      (hSMVT) to carrier-mediated biotin uptake by human proximal tubular epithelial
      cells is not clear. The aim of this study was to address these issues, with the
      human-derived proximal tubular epithelial HK-2 cells used as a model. First, we
      characterized the mechanism of biotin uptake by these cells and obtained evidence
      for involvement of an Na(+)-, temperature-, and energy-dependent carrier-mediated
      uptake system. This system was inhibited by the biotin structural analog
      desthiobiotin, pantothenic acid, and lipoate. These findings suggest involvement
      of the hSMVT system in the uptake process. This was confirmed by demonstrating
      that the hSMVT system is expressed in HK-2 cells at the protein and mRNA levels
      and by selective silencing of the hSMVT gene with the use of gene-specific small
      interfering RNAs, which led to specific and significant inhibition of carrier
      mediated biotin uptake. Of the two recently cloned promoters of the hSMVT gene,
      promoter 1 was more active than promoter 2 in these cells. Pretreatment of HK-2
      cells with modulators of PKC- and Ca(2+)/calmodulin-mediated pathways (but not
      those that modulate PKA-, protein tyrosine kinase-, or nitric oxide-mediated
      pathways) led to significant alterations in biotin uptake. Maintaining the HK-2
      cells in a biotin-deficient growth medium led to a marked upregulation in biotin
      transport, which was associated with an increase in hSMVT protein and RNA levels
      and an increase in activity of the hSMVT promoters. These results demonstrate
      that biotin uptake by human renal epithelial cells occurs via the hSMVT system
      and that the process is regulated by intracellular PKC- and Ca(2+)/calmodulin
      mediated pathways. The uptake process appears to be adaptively regulated by
      extracellular biotin level, which involves transcriptional regulatory
      mechanism(s).

PMID- 15561973
TI  - Substrate specificity of the human renal sodium dicarboxylate cotransporter,
      hNaDC-3, under voltage-clamp conditions.
AB  - Proximal tubule cells extract dicarboxylates from filtrate and blood, using
      cotransporters located in the brush border [sodium dicarboxylate cotransporter
      (NaDC-1)] and basolateral cell membrane (NaDC-3). We expressed the human NaDC-3
      (hNaDC-3) in Xenopus laevis oocytes and characterized it by the two-electrode
      voltage-clamp technique. At -60 mV, succinate (4 carbons) and glutarate (5
      carbons) generated inward currents due to translocation of three sodium ions and
      one divalent dicarboxylate, whereas oxalate (2 carbons) and malonate (3 carbons)
      did not. The cis-dicarboxylate maleate produced currents smaller in magnitude,
      whereas the trans-dicarboxylate fumarate generated currents similar to succinate.
      The substituted succinate derivatives, malate, 2,2- and 2,3-dimethylsuccinate,
      and 2,3-dimercaptosuccinate elicited inward currents, whereas aspartate and
      guanidinosuccinate showed hardly detectable currents. The C-5 dicarboxylates
      glutarate and alpha-ketoglutarate produced larger currents than succinate;
      glutamate and folate failed to cause inward currents. Kinetic analysis revealed,
      at -60 mV, K(0.5) values of 25 +/- 12 microM for succinate and 45 +/- 13 microM
      for alpha-ketoglutarate, values close to the plasma concentration of these
      compounds. For both compounds, the K(0.5) was independent of voltage, whereas the
      maximal current increased with hyperpolarization. As opposed to the rat and
      flounder orthologs, hNaDC-3 was hardly inhibited by lithium concentrations up to
      5 mM. In the absence of sodium, however, lithium can mediate succinate-dependent
      currents. The narrow substrate specificity prevents interaction of drugs with
      dicarboxylate-like structure with hNaDC-3 and ensures sufficient support of the
      proximal tubule cells with alpha-ketoglutarate for anion secretion via organic
      anion transporter 1 or 3.

PMID- 15561974
TI  - EphA2: expression in the renal medulla and regulation by hypertonicity and urea
      stress in vitro and in vivo.
AB  - EphA2, a member of the large family of Eph receptor tyrosine kinases, is highly
      expressed in epithelial tissue and has been implicated in cell-cell and cell
      matrix interactions, as well as cell growth and survival. Expression of EphA2
      mRNA and protein was markedly upregulated by both hypertonic stress and by
      elevated urea concentrations in cells derived from the murine inner medullary
      collecting duct. This upregulation likely required transactivation of the
      epidermal growth factor (EGF) receptor tyrosine kinase and metalloproteinase
      dependent ectodomain cleavage of an EGF receptor ligand, based on pharmacological
      inhibitor studies. A human EphA2 promoter fragment spanning nucleotides -4030 to
      +21 relative to the putative EphA2 transcriptional start site was responsive to
      tonicity but insensitive to urea. A promoter fragment spanning -1890 to +128
      recapitulated both tonicity- and urea-dependent upregulation of expression,
      consistent with transcriptional activation. Neither the bona fide p53 response
      element at approximately -1.5 kb nor a pair of putative TonE elements at
      approximately -3 kb conferred the tonicity responsiveness. EphA2 mRNA and protein
      were expressed at low levels in rat renal cortex but at high levels in the
      collecting ducts of the renal medulla and papilla. Water deprivation in rats
      increased EphA2 expression in renal papilla, whereas dietary supplementation with
      20% urea increased EphA2 expression in outer medulla. These data indicate that
      transcription and expression of the EphA2 receptor tyrosine kinase are regulated
      by tonicity and urea in vitro and suggest that this phenomenon is also operative
      in vivo. Renal medullary EphA2 expression may represent an adaptive response to
      medullary hypertonicity or urea exposure.

PMID- 15561975
TI  - Protease-activated receptor stimulation activates a Ca2+-independent
      phospholipase A2 in bladder microvascular endothelial cells.
AB  - Increased mast cell numbers and mast cell activation represent one of the
      prevalent etiologic theories for interstitial cystitis, an inflammatory condition
      in the bladder. This study was designed primarily to determine whether increased
      mast cell tryptase in the bladder wall may play a role in activating bladder
      endothelial cell phospholipase A(2) (PLA(2)), leading to increased inflammatory
      phospholipid metabolite accumulation, which may propagate the inflammatory
      process. We stimulated human bladder microvascular endothelial cells with
      thrombin or tryptase and measured the activation of PLA(2) and the production of
      multiple membrane phospholipid-derived inflammatory mediators. Thrombin and
      tryptase stimulation resulted in activation of a Ca(2+)-independent PLA(2),
      leading to increased release of arachidonic acid and prostacyclin and increased
      production of platelet-activating factor. These responses were blocked completely
      by pretreatment of human bladder microvascular endothelial cells with the Ca(2+)
      independent PLA(2)-selective inhibitor bromoenol lactone. The combination of
      increased prostacyclin and platelet-activating factor in the bladder circulation
      may result in vasodilation and increased polymorphonuclear leukocyte adherence to
      the endothelium and may facilitate recruitment of polymorphonuclear leukocytes to
      the bladder wall of patients with interstitial cystitis.

PMID- 15561976
TI  - Stimulation of soluble guanylyl cyclase inhibits mesangial cell proliferation and
      matrix accumulation in experimental glomerulonephritis.
AB  - To date, no specific treatment is established in mesangial proliferative
      glomerulonephritis in humans. Specific stimulation of soluble guanylyl cyclase
      (sGC), an enzyme catalyzing the synthesis of cGMP from GTP, can be achieved by
      the novel pyrazolopyridine derivative BAY 41-2272. The effect of sGC stimulation
      via BAY 41-2272 on mesangial proliferation was assessed in vivo using a mesangial
      proliferative glomerulonephritis model in rats (anti-Thy1 model). Renal biopsies,
      as well as glomerular isolates, urine samples, and blood samples were compared in
      BAY 41-2272- and placebo-treated groups during anti-Thy1 nephritis. The sGC
      beta(1)-subunit is upregulated during anti-Thy1 nephritis and mainly confined to
      mesangial areas by immunohistochemistry. Specific therapeutic sGC stimulation
      during anti-Thy1 nephritis in vivo was achieved via BAY 41-2272 treatment as
      demonstrated by increased glomerular cGMP levels causing inhibition of mesangial
      proliferation, glomerular matrix accumulation, and proteinuria compared with
      placebo-treated animals. sGC is tightly regulated in glomeruli during
      experimental glomerulonephritis. Considering its beneficial antiproliferative,
      antifibrotic, and antiproteinuric effect in experimental glomerulonephritis, the
      therapeutic stimulation of sGC could become a promising future goal in mesangial
      proliferative glomerulonephritis in humans.

PMID- 15561977
TI  - Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the
      isolated, perfused rat kidney.
AB  - Heme oxygenase-1 (HO-1) is induced as an adaptive and protective response to
      tissue injury. HO-1 degrades heme into carbon monoxide (CO) and biliverdin; the
      latter is then converted to bilirubin. These reaction products have powerful
      antiapoptotic and antioxidant effects. Manipulation of the HO-1 system by
      administration of micromolar doses of exogenous CO or bilirubin has been
      performed in several organ systems, but the dose-related effects of these
      reaction products have not been investigated in the kidney. The purpose of this
      study was to evaluate the efficacy and dose-related protective effects of 1 or 10
      muM bilirubin flush before a 20-min period of warm ischemia. In an effort to
      minimize interactions with other chemical messengers or organ systems, we elected
      to use an isolated, perfused rat kidney model with an acellular, oxygenated
      perfusate. Using this model, we demonstrated that bilirubin treatment resulted in
      significant improvements in renal vascular resistance, urine output, glomerular
      filtration rate, tubular function, and mitochondrial integrity after ischemia
      reperfusion injury (IRI). Beneficial effects on organ viability were achieved
      most consistently with a dose of 10 muM bilirubin. We conclude that the
      protective effects of HO-1 activity during IRI in the kidney are mediated, at
      least in part, by bilirubin and that pretreatment with micromolar doses of
      bilirubin may offer a simple and inexpensive method to improve renal function
      after IRI.

PMID- 15561978
TI  - Internalization of renal type IIc Na-Pi cotransporter in response to a high
      phosphate diet.
AB  - Dietary phosphate levels regulate the renal brush-border type IIa Na-Pi
      cotransporter. Another Na-Pi cotransporter, type IIc, colocalizes with type IIa
      Na-Pi cotransporter in the apical membrane of renal proximal tubular cells. The
      goal of the present study was to determine whether dietary phosphate levels also
      rapidly regulate the type IIc Na-Pi cotransporter. Type IIa and type IIc
      transporter protein levels were increased in rats chronically fed a low-Pi diet
      compared with those fed a normal-Pi diet. Two hours after beginning a high-Pi
      diet, type IIa transporter levels were decreased, whereas type IIc protein levels
      remained unchanged. Western blot analysis of brush-border membrane prepared 4 h
      after beginning a high-Pi diet showed a significant reduction in type IIc
      transporter protein levels, and immunohistochemistry showed translocation of the
      type IIc-immunoreactive signal from the entire brush border to subapical
      membrane. Membrane fractionation studies revealed a decrease in apical membrane
      type IIc protein without changes in total cortical type IIc protein, which is
      compatible with redistribution of type IIc protein from the apical membrane to
      the dense membrane fraction. The microtubule-disrupting reagent colchicine
      prevented this reduction in apical type IIc transporter at the apical membrane
      but had no effect on type IIa transporter levels. These data suggest that the
      type IIc Na-Pi cotransporter level is rapidly regulated by rapid adaptation to
      dietary Pi in a microtubule-dependent manner. Furthermore, the mechanisms of the
      internalization of the type IIc transporter are distinct from those of the type
      IIa transporter.

PMID- 15561979
TI  - The Jak-STAT pathway stimulated by interferon alpha or interferon beta.
AB  - Type I interferons, such as interferon alpha and interferon beta (IFN-alpha and
      beta), signal through a Janus kinase (Jak) to signal transduction and activator
      of transcription (STAT) pathway to stimulate gene expression. In response to
      ligand binding, the receptors dimerize, Jaks phosphorylate STAT1 and STAT2, which
      then dimerize and interact with a third transcriptional regulator IFN regulatory
      factor 9 (IRF9) to stimulate gene expression. IFN-alpha is the main innate
      antiviral cytokine and is essential for effective immune response to viral
      infection. The animation shows activation of STAT-responsive gene expression in
      response to type I IFNs.

PMID- 15561980
TI  - The Jak-STAT pathway stimulated by interferon gamma.
AB  - Different cytokines stimulate the Janus kinase (Jak) and signal transducer and
      activator of transcription (STAT) pathway. Interferon gamma (IFN-gamma) is a type
      II interferon that triggers antiviral and adaptive immune responses through a Jak
      STAT signaling pathway. These pathways involve a similar paradigm whereby
      cytokine binding to the receptor activates the Jaks, which phosphorylate STATs
      leading to their dimerization, translocation to the nucleus, and activation of
      their transcription factor activity. The animation shows binding of IFN-gamma and
      dimerization of the receptors, activation of Jak1 and Jak2, and phosphorylation
      of STAT1 leading to dimerization, translocation to the nucleus, and stimulation
      of target gene transcription.

PMID- 15561981
TI  - The Jak-STAT pathway stimulated by interleukin 6.
AB  - Signal transducer and activator of transcription 3 (STAT3) is widely expressed
      and activated by a variety of growth-regulating signals as well as diverse
      cytokines that use gp130 signaling receptors. STAT3 is critical for embryonic
      development and stem cell biology, as well as inflammation, growth regulation,
      and multiple immune regulatory and homeostatic functions. The animation shows
      activation of STAT3 in response to interleukin 6 (IL6), a cytokine involved in
      triggering inflammation.

PMID- 15561982
TI  - Differential distribution of allelic variants in cytokine genes among African
      Americans and White Americans.
AB  - Racial disparities in health are largely unexplained. Because many diseases
      causing premature mortality among African Americans are mediated by the immune
      system, the authors explored the race-specific distribution of allelic variants
      in cytokine genes known to stimulate inflammation. The authors studied women
      seeking prenatal care and delivering singletons in uncomplicated first births at
      a US hospital in 1997-2001. A total of 179 African-American women and 396 White
      women were evaluated for functionally relevant allelic variants in cytokine
      genes. African-American women were significantly more likely to carry allelic
      variants known to up-regulate proinflammatory cytokines; odds ratios increased
      with allele dose. Odds ratios for African Americans versus Whites in genotypes up
      regulating proinflammatory interleukin (IL) 1 (IL1A-4845G/G, IL1A-889T/T, IL1B
      3957C/C, and IL1B-511A/A) ranged from 2.1 to 4.9. The proinflammatory cytokine
      interleukin-6 IL6-174 G/G genotype was 36.5 times (95% confidence interval (CI):
      8.8, 151.9) more common among African Americans. Genotypes known to down-regulate
      the antiinflammatory interleukin-10 (IL10-819 T/T and IL10-1082 A/A) were
      elevated 3.5-fold (95% CI: 1.8, 6.6) and 2.8-fold (95% CI: 1.6, 4.9) in African
      Americans. Cytokine genotypes found to be more common in African-American women
      were consistently those that up-regulate inflammation.

PMID- 15561983
TI  - Higher bone mineral density in rural compared with urban dwellers: the NOREPOS
      study.
AB  - Norway has a very high incidence of osteoporotic fractures, with substantial
      regional differences in fracture incidence. The present study evaluated whether
      there are differences in bone mineral density (BMD) between regions in Norway
      with differences in fracture incidence. The authors used data collected in four
      large, population-based, multipurpose studies performed in four regions of Norway
      during 1994-2001. Distal forearm BMD was measured by single energy x-ray
      absorptiometry in 10,667 participants aged 40-75 years. Cross-calibration was
      performed by using the European Forearm Phantom. Mean distal forearm BMD was
      lower in the urban populations of Tromso, Oslo, and Bergen compared with the
      rural county of Nord-Trondelag, whereas there was no difference between the rural
      part of Tromso and Nord-Trondelag. For women, body mass index explained some of
      these differences. The prevalence of low BMD (z score < or = -1) in Oslo, Bergen,
      and urban Tromso, compared with Nord-Trondelag, was 1.6-1.7 times higher in men
      and 1.5-2.0 times higher in women, whereas no significant difference was found
      between rural Tromso and Nord-Trondelag. In this study, higher BMD was found in
      rural compared with urban areas of Norway, which might help explain the
      differences in fracture incidence. There was no apparent north-south gradient in
      BMD.

PMID- 15561984
TI  - Triggering of ventricular tachycardia by meteorologic and emotional stress:
      protective effect of beta-blockers and anxiolytics in men and elderly.
AB  - A circadian pattern with a morning peak and the triggering role of emotional
      stress have been suggested for ventricular arrhythmias. After controlling for
      participant baseline characteristics and medication used, the authors studied the
      association of emotional upset, physical activity, and meteorologic parameters
      with occurrence of ventricular tachycardia (VT) in 457 Croatian participants aged
      11-88 years consecutively assigned to undergo continuous 24-hour Holter
      monitoring. In 2001, multivariate analysis of possible VT precipitators was
      performed separately for men, women, those aged <65 years, and those aged >64
      years. A U-shaped pattern of wind speed (either very weak or very strong), rising
      relative air moisture, falling atmospheric pressure, and emotional upset were
      independent predictors of VT episodes in all participant subgroups. Positive
      association of VT with higher atmospheric temperature or pressure was observed in
      women and elderly. After adjustment for external triggers, a circadian variation
      in VT episodes persisted in women (p = 0.01) and those aged <65 years (p <
      0.0001) only. A protective effect of beta-blockers and anxiolytics was especially
      apparent for men and elderly, as well as an adverse effect of digitalis in women.
      Results suggest that meteorologic and emotional stress could be considered
      external triggers of VT, with age- and sex-dependent susceptibility.

PMID- 15561985
TI  - An ecologic study of prostate-specific antigen screening and prostate cancer
      mortality in nine geographic areas of the United States.
AB  - Ecologic studies of cancer screening examine cancer mortality rates in relation
      to use of population screening. These studies can be confounded by treatment
      patterns or influenced by choice of outcome and time horizon. Interpretation can
      be complicated by uncertainty about when mortality differences might be expected.
      The authors examined these issues in an ecologic analysis of prostate-specific
      antigen (PSA) screening and prostate cancer mortality across nine cancer
      registries in the United States. Results suggested a weak trend for areas with
      greater PSA screening rates to have greater declines in prostate cancer
      mortality; however, the magnitude of this trend varied considerably with the time
      horizon and outcome measure. A computer model was used to determine whether
      divergence of mortality declines would be expected under an assumption of a
      clinically significant survival benefit due to screening. Given a mean lead time
      of 5 years, the model projected that differences in mortality between high- and
      low-use areas should be apparent by 1999 in the absence of other factors
      affecting mortality. The authors concluded that modest differences in PSA
      screening rates across areas, together with additional sources of variation,
      could have produced a negative ecologic result. Ecologic analyses of the
      effectiveness of PSA testing should be interpreted with caution.

PMID- 15561986
TI  - A case-control study of ovarian cancer in relation to infertility and the use of
      ovulation-inducing drugs.
AB  - The authors conducted a population-based, case-control study among women aged 35
      54 years to assess the influence of infertility and use of ovulation-inducing
      drugs on ovarian cancer risk. The study was conducted from 1994 to 1998 in three
      regions (metropolitan Atlanta, Georgia, Detroit, Michigan, and Seattle,
      Washington) and included 378 cases and 1,637 controls. Data were obtained through
      in-person interviews, and analysis was conducted using unconditional logistic
      regression. Among parous women, the authors observed no association of cancer
      risk with a history of infertility, medical evaluation for infertility, specific
      types of infertility, or use of ovulation-inducing drugs. Among nulliparous
      women, risk was increased among women with a history of infertility (odds ratio =
      1.6, 95% confidence interval: 1.0, 2.6), particularly when infertility first
      became manifest relatively late in reproductive life (for first infertility at >
      or =30 years of age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.5); risk
      was not associated with medical evaluation for infertility, specific types of
      infertility, or use of ovulation-inducing drugs. Findings were similar when
      borderline and invasive epithelial tumors were considered separately. While the
      results of this study support the hypothesis that a subset of nulliparous women
      who experience infertility may be at increased risk of ovarian cancer, the
      reasons for this increase in risk remain unclear.

PMID- 15561987
TI  - Job stress and breast cancer risk: the nurses' health study.
AB  - Workers tend to perceive certain features of their jobs as harmful to health and
      are alert to associations between job stress and health outcomes, but few
      observational studies have evaluated the role of job stress in carcinogenesis.
      The authors prospectively assessed the association between job strain, measured
      by Karasek and Theorell's job content questionnaire in four categories (low
      strain, active, passive, and high strain), and breast cancer risk among
      participants in the Nurses' Health Study. A total of 37,562 US female registered
      nurses were followed for up to 8 years (1992-2000), and 1,030 cases of invasive
      breast cancer were ascertained during that period. All participants were still in
      the workforce at baseline and completed the job content questionnaire. Adjusted
      for age, reproductive history, and other breast cancer risk factors, the
      multivariate relative risks of breast cancer, in comparison with women who worked
      in low-strain jobs, were 0.83 (95% confidence interval (CI): 0.69, 0.99) for
      women in active jobs, 0.87 (95% CI: 0.73, 1.04) for women in high-strain jobs,
      and 0.90 (95% CI: 0.76, 1.06) for women in passive jobs. Findings from this study
      indicate that job stress is not related to any increase in breast cancer risk.

PMID- 15561988
TI  - Association of body composition and weight history with breast cancer prognostic
      markers: divergent pattern for Hispanic and non-Hispanic White women.
AB  - Body composition and weight gain are breast cancer risk factors that may
      influence prognosis. The Health, Eating, Activity, and Lifestyle Study was
      designed to evaluate the relations of body composition, weight history, hormones,
      and lifestyle factors to prognosis for women with breast cancer. In the cross
      sectional analysis of this cohort study specific to 150 Hispanic and 466 non
      Hispanic White women in New Mexico diagnosed between 1996 and 1999, the authors
      hypothesized that obesity measures are associated with baseline prognostic
      markers and that these associations are modified by ethnicity. Ethnic-stratified
      multiple logistic regression analyses showed divergent results for a tumor size
      of 1.0 cm or more and, to a lesser extent, positive lymph node status. Among
      Hispanics, the highest quartile for body mass index (29.5 vs. <22.5 kg/m2: odds
      ratio (OR) = 0.16, 95% confidence interval (CI): 0.03, 0.84) and for waist
      circumference (> or =95.0 vs. <78.5 cm: OR = 0.09, 95% CI: 0.01, 0.78) was
      significantly associated with a reduced tumor size. In contrast, for overweight
      and obese non-Hispanic White women, there was an increased association with
      obesity-related measures, particularly striking for the highest quartile of waist
      circumference (OR = 2.76, 95% CI: 1.45, 5.26). These findings suggest that
      Hispanics may have a different breast cancer phenotype than non-Hispanic Whites,
      which associates differently with body composition and weight history.

PMID- 15561989
TI  - Food consumption by children and the risk of childhood acute leukemia.
AB  - The possible relation between child's early diet and risk of childhood leukemia
      has remained largely unexplored. The authors' objective was to determine what
      particular foods consumed early in life (first 2 years) are associated with risk
      of childhood leukemia in a 1995-2002 case-control study of a diverse California
      population. Dietary data were obtained from a questionnaire administered to the
      child's caregiver. Conditional logistic regression was used to analyze 328 case
      control sets matched on age, sex, Hispanic status, and maternal race. Regular
      consumption of oranges/bananas (odds ratio = 0.49, 95% confidence interval: 0.26,
      0.94) and orange juice (odds ratio = 0.54, 95% confidence interval: 0.31, 0.94)
      during the first 2 years of life was associated with a reduction in risk of
      childhood leukemia diagnosed between the ages of 2 and 14 years. Restricting the
      analysis to leukemia diagnosed between the ages of 2 and 5 years reflected a
      similar pattern of reduced risk. No association between eating hot dogs/lunch
      meats and risk of leukemia was found. These results suggest that fruits or fruit
      juices that contain vitamin C and/or potassium may reduce the risk of childhood
      leukemia, especially if they are consumed on a regular basis during the first 2
      years of life.

PMID- 15561990
TI  - Occupational exposures and asthma in 14,000 adults from the general population.
AB  - The association of asthma with occupational exposures was studied in 14,151
      adults, aged 25-59 years, from the general population of the 1975 French
      Pollution Atmospherique et Affections Respiratoires Chroniques (PAARC) Survey.
      Associations of asthma with specific jobs, such as personal care workers,
      waiters, and stock clerks, were observed, with age-, sex-, and smoking-adjusted
      odds ratios between 1.5 and 1.7. Exposures to 18 asthmagenic agents (low and high
      molecular weight and mixed environment) were estimated by an asthma-specific job
      exposure matrix. Risks associated with asthma increased when subjects with
      imprecise estimates of exposure were excluded. Risks increased further with
      increasing specificity of the definition of asthma when considering jobs or
      specific agents, such as industrial cleaning agents, latex, flour, highly
      reactive chemicals, and textiles. For example, for industrial cleaning agents,
      odds ratios increased from 1.55 (95% confidence interval (CI): 1.08, 2.23) for
      "ever asthma," to 2.17 (95% CI: 1.41, 3.34) for asthma onset after age 14 years,
      to 2.35 (95% CI: 1.38, 4.00) for asthma onset after beginning current job, and to
      2.51 (95% CI: 1.33, 4.75) for asthma with airflow limitation. Results underlined
      the importance of the specificity of exposure and asthma definitions and
      indicated a deleterious role of occupational exposure on asthma, especially for
      cleaning agents.

PMID- 15561991
TI  - Intervention-related bias in reporting of food intake by fifth-grade children
      participating in an obesity prevention study.
AB  - Data collected as part of Pathways, a school-based trial for the primary
      prevention of obesity in American Indian children conducted between 1997 and
      2000, were analyzed to examine possible intervention-related bias in food
      reporting. The authors hypothesized that children in the intervention schools may
      have systematically underreported their dietary intake relative to children in
      the control schools. Nutrient intake estimates for lunch derived from record
      assisted 24-hour dietary recalls were compared with intake estimates from
      observed lunch intakes. Reported nutrient intakes were included in regression
      analyses as the dependent variables; observed intake, intervention condition, and
      age were included as independent variables. Results indicated that, among
      females, intervention condition was a significant predictor of reported energy,
      fat, and saturated fatty acid intakes. Independently of observed intake, reported
      lunch energy intake among females in the intervention schools was 66.8 calories
      lower than reported intake among females in the control schools (p = 0.03). These
      findings suggest that investigators should consider bias in reporting of dietary
      intake by intervention condition when conducting diet-focused intervention
      studies. Specifically, enhancing measures that rely on self-reports with
      objective measures of dietary intake would help investigators to evaluate whether
      differential reporting by treatment group has occurred.

PMID- 15561992
TI  - Evaluation of measures of urinary albumin excretion in epidemiologic studies.
AB  - Twenty-four-hour urinary albumin excretion (UAE) is considered the gold standard
      for determining albumin level in epidemiologic studies, but this measure is
      inconvenient and often unavailable. Simpler alternatives include the
      albumin:creatinine ratio (ACR) and urinary albumin concentration (UAC) obtained
      from a single sample. The authors assessed the strengths and weaknesses of ACR
      and UAC as alternatives to UAE using albumin measurements from two 24-hour urine
      samples collected in 1996-1999 from 4,678 participants aged 40-59 years in the
      International Study of Macronutrients and Blood Pressure (17 population samples
      from four countries). The authors compared ACR and UAC with regard to
      correlations with UAE, daily within-person variability, and associations with
      known predictors of UAE. Rank-order correlations of ACR with UAE were 0.949 and
      0.942 for men and women, respectively, versus 0.881 and 0.816 for UAC. Mean
      within-person coefficients of variation were 34.0-40.0% for the three measures,
      with the smallest values being observed for UAC. Average correlations with blood
      pressure were similar for UAE, ACR, and UAC, but the correlation with body mass
      index was lower for ACR (0.118 for ACR and 0.188 for UAC vs. 0.211 for UAE)
      because of high correlation between body mass index and creatinine level. Thus,
      UAC and ACR are acceptable alternatives to the more complex UAE, and the simpler
      UAC may be preferable to ACR in some respects.

PMID- 15561993
TI  - Re: "Application of a new statistical method to derive dietary patterns in
      nutritional epidemiology".

PMID- 15561994
TI  - Re: "Changes in body weight and body fat distribution as risk factors for
      clinical diabetes in US men".

PMID- 15561995
TI  - Systematic analysis of bicistronic reporter assay data.
AB  - Bicistronic reporter assay systems have become a mainstay of molecular biology.
      While the assays themselves encompass a broad range of diverse and unrelated
      experimental protocols, the numerical data garnered from these experiments often
      have similar statistical properties. In general, a primary dataset measures the
      paired expression of two internally controlled reporter genes. The expression
      ratio of these two genes is then normalized to an external control reporter. The
      end result is a 'ratio of ratios' that is inherently sensitive to propagation of
      the error contributed by each of the respective numerical components. The
      statistical analysis of this data therefore requires careful handling in order to
      control for the propagation of error and its potentially misleading effects. A
      careful survey of the literature found no consistent method for the statistical
      analysis of data generated from these important and informative assay systems. In
      this report, we present a detailed statistical framework for the systematic
      analysis of data obtained from bicistronic reporter assay systems. Specifically,
      a dual luciferase reporter assay was employed to measure the efficiency of four
      programmed -1 frameshift signals. These frameshift signals originate from the L-A
      virus, the SARS-associated Coronavirus and computationally identified frameshift
      signals from two Saccharomyces cerevisiae genes. Furthermore, these statistical
      methods were applied to prove that the effects of anisomycin on programmed -1
      frameshifting are statistically significant. A set of Microsoft Excel
      spreadsheets, which can be used as templates for data generated by dual reporter
      assay systems, and an online tutorial are available at our website
      (http://dinmanlab.umd.edu/statistics). These spreadsheets could be easily adapted
      to any bicistronic reporter assay system.

PMID- 15561996
TI  - Bigenic Cre/loxP, puDeltatk conditional genetic ablation.
AB  - Genetic ablation experiments are used to resolve problems regarding cell lineages
      and the in vivo function of certain groups of cells. We describe a two-component
      conditional ablation technology using a mouse carrying an X-linked puDeltatk
      transgene, which is only activated in cells expressing Cre. Ablation of the Cre
      expressing cells can be temporally regulated by the time of ganciclovir (GCV)
      administration. This strategy was demonstrated using a Col2Cre transgenic line.
      Differentiating chondrocytes in bigenic animals could be ablated at different
      developmental stages resulting in disorganized growth plates and dwarfism.
      Macrocephaly, macroglossia and umbilical hernia were also observed in ablated
      18.5 dpc embryos. Crosses between the puDeltatk selector transgenic line and
      existing cre lines will facilitate numerous temporally regulated tissue-specific
      ablation experiments.

PMID- 15561997
TI  - Protein-mediated error correction for de novo DNA synthesis.
AB  - The availability of inexpensive, on demand synthetic DNA has enabled numerous
      powerful applications in biotechnology, in turn driving considerable present
      interest in the de novo synthesis of increasingly longer DNA constructs. The
      synthesis of DNA from oligonucleotides into products even as large as small viral
      genomes has been accomplished. Despite such achievements, the costs and time
      required to generate such long constructs has, to date, precluded gene-length
      (and longer) DNA synthesis from being an everyday research tool in the same
      manner as PCR and DNA sequencing. A critical barrier to low-cost, high-throughput
      de novo DNA synthesis is the frequency at which errors pervade the final product.
      Here, we employ a DNA mismatch-binding protein, MutS (from Thermus aquaticus) to
      remove failure products from synthetic genes. This method reduced errors by >15
      fold relative to conventional gene synthesis techniques, yielding DNA with one
      error per 10 000 base pairs. The approach is general, scalable and can be
      iterated multiple times for greater fidelity. Reductions in both costs and time
      required are demonstrated for the synthesis of a 2.5 kb gene.

PMID- 15561998
TI  - Mining SAGE data allows large-scale, sensitive screening of antisense transcript
      expression.
AB  - As a growing number of complementary transcripts, susceptible to exert various
      regulatory functions, are being found in eukaryotes, high throughput analytical
      methods are needed to investigate their expression in multiple biological
      samples. Serial Analysis of Gene Expression (SAGE), based on the enumeration of
      directionally reliable short cDNA sequences (tags), is capable of revealing
      antisense transcripts. We initially detected them by observing tags that mapped
      on to the reverse complement of known mRNAs. The presence of such tags in
      individual SAGE libraries suggested that SAGE datasets contain latent information
      on antisense transcripts. We raised a collection of virtual tags for mining these
      data. Tag pairs were assembled by searching for complementarities between 24-nt
      long sequences centered on the potential SAGE-anchoring sites of well-annotated
      human expressed sequences. An analysis of their presence in a large collection of
      published SAGE libraries revealed transcripts expressed at high levels from both
      strands of two adjacent, oppositely oriented, transcription units. In other
      cases, the respective transcripts of such cis-oriented genes displayed a mutually
      exclusive expression pattern or were co-expressed in a small number of libraries.
      Other tag pairs revealed overlapping transcripts of trans-encoded unique genes.
      Finally, we isolated a group of tags shared by multiple transcripts. Most of them
      mapped on to retroelements, essentially represented in humans by Alu sequences
      inserted in opposite orientations in the 3'UTR of otherwise different mRNAs.
      Registering these tags in separate files makes possible computational searches
      focused on unique sense-antisense pairs. The method developed in the present work
      shows that SAGE datasets constitute a major resource of rapidly investigating
      with high sensitivity the expression of antisense transcripts, so that a single
      tag may be detected in one library when screening a large number of biological
      samples.

PMID- 15561999
TI  - Genomewide linkage searches for Mendelian disease loci can be efficiently
      conducted using high-density SNP genotyping arrays.
AB  - Genomewide linkage searches aimed at identifying disease susceptibility loci are
      generally conducted using 300-400 microsatellite markers. Genotyping bi-allelic
      single nucleotide polymorphisms (SNPs) provides an alternative strategy. The
      availability of dense SNP maps coupled with recent technological developments in
      highly paralleled SNP genotyping makes it practical to now consider the use of
      these markers for whole-genome genetic linkage analyses. Here, we report the
      findings from three successful genomewide linkage analyses of families
      segregating autosomal recessively inherited neonatal diabetes, craniosynostosis
      and dominantly inherited renal dysplasia using the Affymetrix 10K SNP array. A
      single locus was identified for each disease state, two of which are novel. The
      performance of the SNP array, both in terms of efficiency and precision,
      indicates that such platforms will become the dominant technology for performing
      genomewide linkage searches.

PMID- 15562000
TI  - In situ imaging and isolation of proteins using dsDNA oligonucleotides.
AB  - As proteomics initiatives mature, the need will arise for the multiple
      visualization of proteins and supramolecular complexes within their true context,
      in situ. Single-stranded DNA and RNA aptamers can be used for low resolution
      imaging of cellular receptors and cytoplasmic proteins by light microscopy (LM).
      These techniques, however, cannot be applied to the imaging of nuclear antigens
      as these single-stranded aptamers bind endogenous RNA and DNA with high affinity.
      To overcome this problem, we have developed a novel method for the in situ
      detection of proteins using double-stranded DNA oligonucleotides. To demonstrate
      this system we have utilized the prokaryotic DNA-binding proteins LacI and TetR
      as peptide tags to image fusion proteins in situ using dsDNA oligonucleotides
      encoding either the Lac or Tet operator. Using fluorescent and fluorogold dsDNA
      oligonucleotides, we localized within the nucleus a TetR-PML fusion protein
      within promyelocytic leukaemia protein (PML) bodies by LM and a LacI-SC35 fusion
      protein within nuclear speckles by correlative light and electron microscopy
      (LM/EM). Isolation of LacI-SC35 was also accomplished by using biotinylated dsDNA
      and streptavidin sepharose. The use of dsDNA oligonucleotides should complement
      existing aptamer in situ detection techniques by allowing the multiple detection
      and localization of nuclear proteins in situ and at high resolution.

PMID- 15562001
TI  - The impact of SNPs on the interpretation of SAGE and MPSS experimental data.
AB  - Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature
      Sequencing (MPSS) are powerful techniques for gene expression analysis. A crucial
      step in analyzing SAGE and MPSS data is the assignment of experimentally obtained
      tags to a known transcript. However, tag to transcript assignment is not a
      straightforward process since alternative tags for a given transcript can also be
      experimentally obtained. Here, we have evaluated the impact of Single Nucleotide
      Polymorphisms (SNPs) on the generation of alternative SAGE and MPSS tags. This
      was achieved through the construction of a reference database of SNP-associated
      alternative tags, which has been integrated with SAGE Genie. A total of 2020 SNP
      associated alternative tags were catalogued in our reference database and at
      least one SNP-associated alternative tag was observed for approximately 8.6% of
      all known human genes. A significant fraction (61.9%) of these alternative tags
      matched a list of experimentally obtained tags, validating their existence. In
      addition, the origin of four out of five SNP-associated alternative MPSS tags was
      experimentally confirmed through the use of the GLGI-MPSS protocol (Generation of
      Long cDNA fragments for Gene Identification). The availability of our SNP
      associated alternative tag database will certainly improve the interpretation of
      SAGE and MPSS experiments.

PMID- 15562002
TI  - The preferential binding of histone H1 to DNA scaffold-associated regions is
      determined by its C-terminal domain.
AB  - Histone H1 preferentially binds and aggregates scaffold-associated regions (SARs)
      via the numerous homopolymeric oligo(dA).oligo(dT) tracts present within these
      sequences. Here we show that the mammalian somatic subtypes H1a,b,c,d,e and H1
      degrees and the male germline-specific subtype H1t, all preferentially bind to
      the Drosophila histone SAR. Experiments with the isolated domains show that
      whilst the C-terminal domain maintains strong and preferential binding, the N
      terminal and globular domains show weak binding and poor specificity for the SAR.
      The preferential binding of SAR by the H1 molecule thus appears to be determined
      by its highly basic C-terminal domain. Salmine, a typical fish protamine, which
      could have its evolutionary origin in histone H1, also shows preferential binding
      to the SAR. The interaction of distamycin, a minor groove binder with high
      affinity for homopolymeric oligo(dA).oligo(dT) tracts, abolishes preferential
      binding of the C-terminal domain of histone H1 and protamine to the SAR,
      suggesting the involvement of the DNA minor groove in the interaction.

PMID- 15562003
TI  - RNA aptamers selected against the receptor activator of NF-kappaB acquire general
      affinity to proteins of the tumor necrosis factor receptor family.
AB  - The receptor activator of NF-kappaB (RANK) is a member of the tumor necrosis
      factor (TNF) receptor family and acts to cause osteoclastgenesis through the
      interaction with its ligand, RANKL. We isolated RNA aptamers with high affinity
      to human RANK by SELEX. Sequence and mutational analysis revealed that the
      selected RNAs form a G-quartet conformation that is crucial for binding to RANK.
      When the aptamer binding to RANK was challenged by RANKL, there was no
      competition between the aptamer and RANKL. Instead, the formation of a ternary
      complex, aptamer-RANK-RANKL, was detected by a spin down assay and by BIAcore
      surface plasmon resonance analysis. Moreover, the selected aptamer efficiently
      bound to other TNF receptor family proteins, such as TRAIL-R2, CD30, NGFR as well
      as osteoprotegerin, a decoy receptor for RANK. These results suggest that the
      selected aptamer recognizes not the ligand-binding site, but rather a common
      structure conserved in the TNF receptor family proteins.

PMID- 15562004
TI  - Type II restriction endonuclease R.KpnI is a member of the HNH nuclease
      superfamily.
AB  - The restriction endonuclease (REase) R.KpnI is an orthodox Type IIP enzyme, which
      binds to DNA in the absence of metal ions and cleaves the DNA sequence 5'-GGTAC-
      C-3' in the presence of Mg2+ as shown generating 3' four base overhangs.
      Bioinformatics analysis reveals that R.KpnI contains a betabetaalpha-Me-finger
      fold, which is characteristic of many HNH-superfamily endonucleases, including
      homing endonuclease I-HmuI, structure-specific T4 endonuclease VII, colicin E9,
      sequence non-specific Serratia nuclease and sequence-specific homing endonuclease
      I-PpoI. According to our homology model of R.KpnI, D148, H149 and Q175 correspond
      to the critical D, H and N or H residues of the HNH nucleases. Substitutions of
      these three conserved residues lead to the loss of the DNA cleavage activity by
      R.KpnI, confirming their importance. The mutant Q175E fails to bind DNA at the
      standard conditions, although the DNA binding and cleavage can be rescued at pH
      6.0, indicating a role for Q175 in DNA binding and cleavage. Our study provides
      the first experimental evidence for a Type IIP REase that does not belong to the
      PD...D/EXK superfamily of nucleases, instead is a member of the HNH superfamily.

PMID- 15562005
TI  - Preferential accessibility to specific genomic loci for the repair of double
      strand breaks in human cells.
AB  - The dynamic organization of the human genome in the nucleus is gaining
      recognition as a determining factor in its functional regulation. In order to be
      expressed, replicated or repaired, a genomic locus has to be present at the right
      place at the right time. In the present study, we have investigated the choice of
      a double-strand break (DSB) repair partner for a given genomic loci in an ATM
      deficient human fibroblast cell line. We found that partner choice is restricted
      such that a given genomic locus preferentially uses certain sites in the genome
      to repair itself. These preferential sites can be in the vicinity of the damage
      site or megabases away or on other chromosomes entirely, while potential sites
      closer to the break along the length of the chromosome can be ignored. Moreover,
      there can be more than a 10-fold difference in usage between repair sites located
      only 10 kb apart. Interestingly, arms of a given chromosome are less accessible
      to one another than to other chromosomes. Altogether, these results indicate that
      the accessibility between genomic sites in the human genome during DSB repair is
      specific and conserved in a cell population.

PMID- 15562006
TI  - The relative flexibility of B-DNA and A-RNA duplexes: database analysis.
AB  - An extensive analysis of structural databases is carried out to investigate the
      relative flexibility of B-DNA and A-RNA duplexes in crystal form. Our results
      show that the general anisotropic concept of flexibility is not very useful to
      compare the deformability of B-DNA and A-RNA duplexes, since the flexibility
      patterns of B-DNA and A-RNA are quite different. In other words, 'flexibility' is
      a dangerous word for describing macromolecules, unless it is clearly defined. A
      few soft essential movements explain most of the natural flexibility of A-RNA,
      whereas many are necessary for B-DNA. Essential movements occurring in naked B
      DNAs are identical to those necessary to deform DNA in DNA-protein complexes,
      which suggest that evolution has designed DNA-protein complexes so that B-DNA is
      deformed according to its natural tendency. DNA is generally more flexible, but
      for some distortions A-RNA is easier to deform. Local stiffness constants
      obtained for naked B-DNAs and DNA complexes are very close, demonstrating that
      global distortions in DNA necessary for binding to proteins are the result of the
      addition of small concerted deformations at the base-pair level. Finally, it is
      worth noting that in general the picture of the relative deformability of A-RNA
      and DNA derived from database analysis agrees very well with that derived from
      state of the art molecular dynamics (MD) simulations.

PMID- 15562007
TI  - The influence of androgen deprivation therapy on metabolism in patients with
      prostate cancer.
AB  - The effects of androgen deprivation therapy (ADT) include not only suppression of
      tumor growth, but also adverse effects on various bodily functions. The aim of
      this study was to determine the metabolic effects of ADT in patients with
      nonmetastatic prostate cancer. Forty-nine men with prostate cancer were treated
      with ADT before beginning radical therapy for 6 months. Body weight, peripheral
      red blood cell counts, hemoglobin, hematocrit, fasting blood sugar, serum total
      cholesterol, blood urea nitrogen, uric acid, compensated calcium, inorganic
      phosphorus, bone-specific alkaline phosphatase, urinary deoxypyridinoline, and
      radial bone density determined using dual energy x-ray absorptiometry were
      examined before and 6 months after ADT treatment. Body weight (P = 0.037) and the
      levels of fasting blood sugar (P = 0.014), serum total cholesterol (P = 0.017),
      blood urea nitrogen (P = 0.030), compensated calcium (P < 0.001), inorganic
      phosphorus (P < 0.001), bone-specific alkaline phosphatase (P < 0.001), and
      compensated urinary deoxypyridinoline (P < 0.001) increased significantly.
      Peripheral red blood cell counts (P < 0.001), hemoglobin level (P < 0.001),
      hematocrit (P < 0.001), uric acid (P < 0.001), and radial bone density (P =
      0.023) decreased significantly. These effects of ADT on various bodily functions
      warrant systematic study in clinical trials. We should be aware of the far
      reaching consequences of ADT and incorporate strategies for preventing and
      managing adverse effects into routine practice.

PMID- 15562008
TI  - Molecular screening and association analyses of the interleukin 6 receptor gene
      variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity.
AB  - IL-6 levels and polymorphisms have been implicated in type 2 diabetes mellitus
      (T2DM) and insulin resistance. The IL-6 receptor (IL-6R) comprises two subunits,
      IL-6R and gp130, of which IL-6R confers specificity to IL-6 action and is located
      in a region of replicated linkage to T2DM on chromosome 1q21. We screened this
      gene for variation in Northern European Caucasian and African-American ethnic
      groups. We identified 11 variants with a minor allele frequency over 5%,
      including two amino acid changes (D358A and V385I) and four variants in the 3'
      untranslated region. No variant was associated with obesity or measures of
      insulin sensitivity, but two single nucleotide polymorphisms in the 3'
      untranslated region showed a trend to an association with T2DM in all Caucasians,
      and three single nucleotide polymorphisms, including D358A, showed a trend (P <
      0.06) to an association with T2DM among the subset of Northern European
      Caucasians. Variant V385I was unique to African-Americans and was significantly
      associated with diabetes and diabetic nephropathy (P < 0.05). Among individuals
      heterozygous for the four variants in the transcribed sequence, one allele was
      significantly overrepresented, thus suggesting the existence of a regulatory
      variant controlling mRNA stability or expression. IL-6R is not likely to explain
      the linkage to diabetes in this region, but our work supports a minor role of
      variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA
      levels and possibly levels of soluble IL-6R.

PMID- 15562009
TI  - Genotype-phenotype correlations in children with congenital hyperinsulinism due
      to recessive mutations of the adenosine triphosphate-sensitive potassium channel
      genes.
AB  - Congenital hyperinsulinism (HI) is most commonly caused by recessive mutations of
      the pancreatic beta-cell ATP-sensitive potassium channel (K(ATP)), encoded by two
      genes on chromosome 11p, SUR1 and Kir6.2. The two mutations that have been best
      studied, SUR1 g3992-9a and SUR1 delF1388, are null mutations yielding
      nonfunctional channels and are characterized by nonresponsiveness to diazoxide, a
      channel agonist, and absence of acute insulin responses (AIRs) to tolbutamide, a
      channel antagonist, or leucine. To examine phenotypes of other K(ATP) mutations,
      we measured AIRs to calcium, leucine, glucose, and tolbutamide in infants with
      recessive SUR1 or Kir6.2 mutations expressed as diffuse HI (n = 8) or focal HI (n
      = 14). Of the 24 total mutations, at least seven showed evidence of residual
      K(ATP) channel function. This included positive AIR to both tolbutamide and
      leucine in diffuse HI cases or positive AIR to leucine in focal HI cases. One
      patient with partial K(ATP) function also responded to treatment with the channel
      agonist, diazoxide. Six of the seven patients with partial defects had amino acid
      substitutions or insertions; whereas, the other patient was compound heterozygous
      for two premature stop codons. These results indicate that some K(ATP) mutations
      can yield partially functioning channels, including cases of hyperinsulinism that
      are fully responsive to diazoxide therapy.

PMID- 15562010
TI  - Single injections of vascular endothelial growth factor trap block ovulation in
      the macaque and produce a prolonged, dose-related suppression of ovarian
      function.
AB  - Follicular development is associated with intense angiogenesis and increased
      permeability of blood vessels under the control of locally produced angiogenic
      factors such as vascular endothelial growth factor (VEGF). The aim of the present
      study was to evaluate the effects of transient inhibition of VEGF on pituitary
      ovarian function in the macaque. Animals were given a single, iv injection of a
      potent, receptor-based VEGF antagonist, the VEGF Trap. VEGF Trap was given at a
      dose of 4, 1, or 0.25 mg/kg in the midfollicular phase or at 1.0 mg/kg in the
      late follicular phase. Controls were treated with vehicle or a control protein,
      recombinant human Fc (1 mg/kg). Blood samples were collected once daily for 12 d
      after injection, and three times per week thereafter until normal ovulatory
      cycles had resumed. The VEGF Trap produced a rapid suppression of estradiol and
      inhibin B concentrations at all doses tested, followed by a marked and sustained
      increase in LH and FSH. Ovulation and formation of a functional corpus luteum, as
      evidenced by increased serum progesterone levels, failed to occur at the
      anticipated time. Normal ovarian activity resumed when plasma concentrations of
      unbound VEGF Trap fell below about 1 mg/liter. When treatment was initiated in
      the midfollicular phase, control macaques ovulated 7.2 +/- 0.4 d later, but
      ovulation was delayed in a dose-dependent manner by VEGF Trap, occurring 23 +/-
      0.7, 30 +/- 1.4, and 43 +/- 0.8 d after injection of 0.25, 1, or 4 mg/kg,
      respectively. Thus, the VEGF Trap exerts a potent, dose-dependent, but reversible
      inhibitory effect on ovarian function.

PMID- 15562011
TI  - Aurora B overexpression associates with the thyroid carcinoma undifferentiated
      phenotype and is required for thyroid carcinoma cell proliferation.
AB  - Alterations in chromosome number (aneuploidy) are common in human neoplasias.
      Loss of mitotic regulation is believed to induce aneuploidy in cancer cells and
      act as a driving force during the malignant progression. The serine/theronine
      protein kinases of aurora family genes play a critical role in the regulation of
      key cell cycle processes. Aurora B mediates chromosome segregation by ensuring
      orientation of sister chromatids and overexpression of Aurora B in diploid human
      cells NHDF (normal human diploid fibroblast) induces multinuclearity. We analyzed
      Aurora B expression in human thyroid carcinomas. Cell lines originating from
      different histotypes showed an increase in Aurora B expression.
      Immunohistochemical analysis of archive samples showed a high expression of
      Aurora B in anaplastic thyroid carcinomas; conversely, Aurora B expression was
      not detectable in normal thyroid tissue. Real-time PCR analysis confirmed a
      strong expression of Aurora B in anaplastic thyroid carcinomas. The block of
      Aurora B expression induced by RNA interference or by using an inhibitor of
      Aurora kinase activity significantly reduced the growth of thyroid anaplastic
      carcinoma cells.

PMID- 15562012
TI  - Polyol concentrations in the fluid compartments of the human conceptus during the
      first trimester of pregnancy: maintenance of redox potential in a low oxygen
      environment.
AB  - Polyols are sugar alcohols formed by the reduction of aldoses and ketoses.
      Production is favored under conditions of low oxygenation, when it may provide an
      alternative means to production of lactate for regulating the oxidation-reduction
      balance of pyridine nucleotides. Polyols also act as important organic osmolytes
      and as precursors of cell membrane components. We measured free sugar and polyol
      concentrations in matched samples of maternal serum, intervillous fluid, coelomic
      fluid, and amniotic fluid from normal human pregnancies at 5-12 wk gestational
      age. The concentrations of fructose, inositol, sorbitol, erythritol, and ribitol
      were significantly higher in coelomic and amniotic fluids than in maternal serum,
      but the reverse was the case for glucose and glycerol. Intervillous fluid
      concentrations of inositol, mannitol, and sorbitol were also significantly higher
      than those in maternal serum. These results demonstrate that the polyol pathway,
      considered vestigial in adult tissues, is highly active in the human conceptus
      during early pregnancy. The pathway may serve to maintain ATP concentrations and
      cellular redox potential while the embryo develops in a low oxygen environment.
      Polyols may also play important physiological roles in development of the human
      conceptus, possibly drawing water and solutes across the placenta and expanding
      the gestational sac.

PMID- 15562013
TI  - Bone mineral density in childhood survivors of acute lymphoblastic leukemia
      treated without cranial irradiation.
AB  - Adult survivors of childhood acute lymphoblastic leukemia (ALL) whose treatment
      included cranial irradiation (XRT) have reduced bone mineral density (BMD). Fifty
      three survivors of ALL (aged 6-17 yr; 22 males and 31 females), who had completed
      their treatment without XRT, at least 1 yr previously, and 187 (5-19 yr; 86 males
      and 101 females) healthy controls were examined with dual energy x-ray
      absorptiometry of the total body and L1-L4 vertebrae and peripheral quantitative
      computer tomography at the distal and midradial sites. The total body and lumbar
      spine BMDs did not differ between the ALL survivors and controls. Distal radial
      trabecular BMD (difference, -0.080 mg/cm(3); 95% confidence interval, -0.139 to 
      0.020; P = 0.009), but not total BMD (difference, -0.006 mg/cm(3); confidence
      interval, -0.051 to 0.039; P = 0.80), was lower in ALL survivors compared with
      controls. At the midradial site, both endosteal (11% larger; P = 0.0001) and
      periosteal (4% larger; P = 0.001) circumferences were greater, and cortical
      thickness was thinner by 6% (P = 0.006) in the ALL subjects, leading to an
      increase in the axial moment of inertia in the ALL subjects (difference, 13%; P =
      0.008). In conclusion, BMD, except at the radius, is normal in childhood
      survivors of ALL treated without XRT. At the midradial site, we speculate that
      ALL or its treatment resulted in endosteal bone loss and cortical bone thinning,
      but the axial moment of inertia and, hence, strength was maintained as a result
      of bone gain at the periosteal surface.

PMID- 15562014
TI  - Human lymphocyte-synthesized melatonin is involved in the regulation of the
      interleukin-2/interleukin-2 receptor system.
AB  - Since melatonin was first isolated in 1958 up to the last few years, this
      substance was considered a hormone exclusive to the pineal gland. Although
      melatonin has lately been identified in a large number of extrapineal sites, its
      potential biological actions have not yet been studied. This paper shows that
      human lymphocyte-synthesized melatonin plays a crucial role modulating IL-2/IL-2
      receptor system because when blocking melatonin biosynthesis by the tryptophan
      hydroxylase inhibitor, parachlorophenylalanine, both IL-2 and IL-2 receptor
      levels fell, restoring them by adding exogenous melatonin. Moreover, we
      demonstrated that this endogenous melatonin interfered with the exogenous
      melatonin effect on IL-2 production. Melatonin exerted these effects by a
      receptor-mediated action mechanism because both IL-2 and IL-2 receptor
      expressions significantly decreased when lymphocytes were incubated in the
      presence of the specific membrane and/or nuclear melatonin receptor antagonists,
      luzindole, and/or CGP 55644, respectively. Finally, we made the real significance
      of the membrane melatonin receptors in this process clear, so prostaglandin E(2)
      induced inhibition on IL-2 production increased when we blocked the membrane
      receptors using luzindole. In conclusion, these data show that endogenous
      melatonin is an essential part for an accurate response of human lymphocytes
      through the modulation of IL-2/IL-2 receptor system.

PMID- 15562015
TI  - Lack of effect of calcium intake on the 25-hydroxyvitamin d response to oral
      vitamin D3.
AB  - This study was conducted to examine the effect of calcium intake on the rise in
      serum 25-hydroxyvitamin D [25(OH)D] levels in response to supplemental vitamin
      D(3). Fifty-two healthy older men and women were randomly assigned to take
      calcium (500 mg twice daily with meals) or placebo tablets for 90 d between
      October 1 and the end of March. All participants were placed on 800 IU/d (20
      microg/d) vitamin D(3). Serum 25(OH)D measurements were made at baseline and on d
      30, 60, and 90. The mean baseline 25(OH)D values were 19.2 +/- 6.4 ng/ml (47.9 +/
      15.9 nmol/liter) in the calcium group and 19.6 +/- 6.7 ng/ml (49.1 +/- 16.7
      nmol/liter) in the control group (P = 0.808). The difference in pattern of change
      in 25(OH)D was not statistically significant (group by time interaction, P =
      0.651); the calcium group increased 6.5 +/- 5.9 ng/ml (16.2 +/- 14.8 nmol/liter;
      P < 0.001), and the control group increased 6.6 +/- 7.0 ng/ml (16.6 +/- 17.4
      nmol/liter; P < 0.001). The 95% confidence interval for difference in mean
      increase, calcium vs. control, was -3.8 +/- 3.5 ng/ml (-9.6, 8.7) nmol/liter. In
      older men and women, the level of calcium intake, within the range of 500-1500
      mg/d, does not have an important effect on the rise in serum 25(OH)D that occurs
      in response to 800 IU (20 microg)/d vitamin D(3).

PMID- 15562016
TI  - Octreotide (long-acting release formulation) treatment in patients with graves'
      orbitopathy: clinical results of a four-month, randomized, placebo-controlled,
      double-blind study.
AB  - There are few effective, safe modalities for the management of Graves'
      ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease.
      Somatostatin analogs inhibit lymphocyte proliferation and activation, and
      accumulate in the orbital tissue of patients with GO. A double-blind, placebo
      controlled study of a long-acting somatostatin analog [16 wk of long-acting
      release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients
      with mild active GO with the aim of preventing deterioration and precluding the
      need for more aggressive therapeutic modalities, such as glucocorticoids or
      radiotherapy. No treatment effect was observed for the primary end point (a
      composite parameter defining the outcome as either success or failure on the
      basis of changes in class/grade of the severity index and Clinical Activity Scale
      of GO). The Clinical Activity Scale score was reduced for patients treated with
      octreotide-LAR, but without any significant difference with respect to patients
      receiving placebo. However, octreotide-LAR significantly reduced proptosis (as
      measured by exophthalmometry). This was associated with nonsignificant
      differences in favor of octreotide-LAR in a series of proptosis-related
      parameters: class III grade, opening of the upper eyelid, the difference in
      ocular pressure between primary position and upgaze, and extraocular muscle
      involvement. By magnetic resonance imaging evaluation the extraocular muscle
      volumes appeared reduced, but nonsignificantly. No significant correlation
      between the initial uptake of the somatostatin analog indium-labeled and the
      response to treatment was observed. One patient in the octreotide-LAR group
      developed gallstones. In this study, octreotide-LAR did not seem suitable to
      mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis,
      one of the most debilitating symptoms of GO. Additional studies are warranted to
      define the benefit to risk ratio of the somatostatin analogs in this indication.

PMID- 15562017
TI  - Relationship of estradiol and inhibin to the follicle-stimulating hormone
      variability in hypergonadotropic hypogonadism or premature ovarian failure.
AB  - Recent studies have demonstrated the presence of ovarian follicular development
      in up to 78% of women with premature ovarian failure (POF). The purpose of this
      study was to examine the control of FSH by estradiol and inhibin secretion from
      these follicles. Weekly blood samples were collected in conjunction with
      assessment of ovarian follicle development by ultrasound for at least 12 wk in 49
      subjects with POF. Results were compared with those of 44 normal cycling women.
      Ovulatory cycles occurred in 24 subjects (49%) with POF. These ovulatory cycles
      were characterized by higher FSH and lower inhibin B and inhibin A levels,
      whereas estradiol levels were higher compared with those in normal women.
      Follicles developed in the absence of ovulation in 18 women (37%) with POF,
      whereas the ovaries were inactive in seven women (14%). FSH levels were lower in
      POF women with ovulatory or anovulatory follicle development compared with levels
      in women with inactive ovaries. These findings demonstrate that ovulatory cycles
      in women with POF are characterized by a persistent elevation in FSH compared
      with levels in normal cycling women. The association of increased FSH with lower
      levels of inhibin B and inhibin A, but higher estradiol levels provides
      additional evidence for an important physiological role of the inhibins in the
      negative feedback control of FSH. These data also demonstrate the variability in
      FSH levels as a function of underlying follicular development in women with POF.

PMID- 15562018
TI  - Human sperm express cannabinoid receptor Cb1, the activation of which inhibits
      motility, acrosome reaction, and mitochondrial function.
AB  - Cannabinoids and endocannabinoids negatively influence sperm functions. These
      substances have been demonstrated in many mammalian tissues, including male and
      female reproductive tracts, and previous studies have shown the presence of
      functional receptors for cannabinoids in human sperm. The present study, by means
      of RT-PCR and Western blot techniques, demonstrates that human sperm express the
      CB(1), but not CB(2), cannabinoid receptor (CB-R) subtype located in the head and
      middle piece of the sperm. The activation of this receptor by anandamide reduces
      sperm motility and inhibits capacitation-induced acrosome reaction. Activation of
      the CB(1)-R did not induce any variation in sperm intracellular calcium
      concentrations, but produced a rapid plasma membrane hyperpolarization that was
      reduced by the K(+) channel blocker tetraethylammonium. The effects of anandamide
      on human sperm motility were dependent on the reduction of sperm mitochondrial
      activity as determined by rhodamine 123 fluorescence. The specificity of
      anandamide effects in human sperm were confirmed by the effects of the CB(1)-R
      antagonist SR141716. These findings provide additional evidence that human sperm
      express functional CB(1)-R, the activation of which negatively influences
      important sperm functions, and suggest a possible role for the cannabinoid system
      in the pathogenesis of some forms of male infertility.

PMID- 15562019
TI  - The insulin gene variable number tandem repeat and risk of type 2 diabetes in a
      population-based sample of families and unrelated men and women.
AB  - Abnormalities in insulin regulation are central to the pathogenesis of type 2
      diabetes. We assessed variation in the insulin gene variable number tandem repeat
      (INS VNTR) minisatellite (using the -23Hph1 A/T single nucleotide polymorphism)
      as a risk factor for 92 cases of incident type 2 diabetes in 883 unrelated
      Framingham Heart Study (FHS) subjects and in a separate sample of 698 members of
      282 FHS nuclear families with 62 diabetes cases. In the unrelated sample, the 
      23Hph1 TT genotype frequency was 8.0% and was associated with a diabetes hazard
      ratio of 1.89 [95% confidence interval (CI), 1.01-3.52; P = 0.045] compared with
      the AA genotype using diabetes age of onset as the time failure variable in a
      proportional hazards model adjusted for age, offspring sex, body mass index,
      parental diabetes, and sex by parental diabetes interactions. In sex-stratified
      analyses, TT increased risk for diabetes in women (hazard ratio, 4.25; 95% CI,
      1.76-10.3), but not men (hazard ratio, 1.01; 95% CI, 0.39-2.60). Using a family
      based association test to assess transmission disequilibrium in the sample of
      related subjects, the age- and sex-adjusted z-score for diabetes associated with
      the T allele was 2.07 (P = 0.04), and a family-based association test using age
      of onset in a proportional hazards model was also statistically significant (P =
      0.03), indicating that increased risk of diabetes was not attributable to
      population admixture. These data support the hypothesis that the INS VNTR is a
      genetic risk factor for type 2 diabetes, with the TT genotype accounting for
      about 6.6% of cases in the FHS population.

PMID- 15562020
TI  - Older men are as responsive as young men to the anabolic effects of graded doses
      of testosterone on the skeletal muscle.
AB  - Although testosterone levels and muscle mass decline with age, many older men
      have serum testosterone level in the normal range, leading to speculation about
      whether older men are less sensitive to testosterone. We determined the
      responsiveness of androgen-dependent outcomes to graded testosterone doses in
      older men and compared it to that in young men. The participants in this
      randomized, double-blind trial were 60 ambulatory, healthy, older men, 60-75 yr
      of age, who had normal serum testosterone levels. Their responses to graded doses
      of testosterone were compared with previous data in 61 men, 19-35 yr old. The
      participants received a long-acting GnRH agonist to suppress endogenous
      testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate
      weekly for 20 wk. Fat-free mass, fat mass, muscle strength, sexual function,
      mood, visuospatial cognition, hormone levels, and safety measures were evaluated
      before, during, and after treatment. Of 60 older men who were randomized, 52
      completed the study. After adjusting for testosterone dose, changes in serum
      total testosterone (change, -6.8, -1.9, +16.1, +49.5, and +101.9 nmol/liter at
      25, 50, 125, 300, and 600 mg/wk, respectively) and hemoglobin (change, -3.6,
      +9.9, +20.9, +12.6, and +29.4 g/liter at 25, 50, 125, 300, and 600 mg/wk,
      respectively) levels were dose-related in older men and significantly greater in
      older men than young men (each P < 0.0001). The changes in FFM (-0.3, +1.7, +4.2,
      +5.6, and +7.3 kg, respectively, in five ascending dose groups) and muscle
      strength in older men were correlated with testosterone dose and concentrations
      and were not significantly different in young and older men. Changes in fat mass
      correlated inversely with testosterone dose (r = -0.54; P < 0.001) and were
      significantly different in young vs. older men (P < 0.0001); young men receiving
      25- and 50-mg doses gained more fat mass than older men (P < 0.0001). Mood and
      visuospatial cognition did not change significantly in either group. Frequency of
      hematocrit greater than 54%, leg edema, and prostate events were numerically
      higher in older men than in young men. Older men are as responsive as young men
      to testosterone's anabolic effects; however, older men have lower testosterone
      clearance rates, higher increments in hemoglobin, and a higher frequency of
      adverse effects. Although substantial gains in muscle mass and strength can be
      realized in older men with supraphysiological testosterone doses, these high
      doses are associated with a high frequency of adverse effects. The best trade-off
      was achieved with a testosterone dose (125 mg) that was associated with high
      normal testosterone levels, low frequency of adverse events, and significant
      gains in fat-free mass and muscle strength.

PMID- 15562021
TI  - Risk of second brain tumor after conservative surgery and radiotherapy for
      pituitary adenoma: update after an additional 10 years.
AB  - We assessed the risk of second brain tumors in a cohort of patients with
      pituitary adenoma treated with conservative surgery and external beam
      radiotherapy. Four hundred and twenty-six patients (United Kingdom residents)
      with pituitary adenomas received radiotherapy at the Royal Marsden Hospital (RMH)
      between 1962 and 1994. They were followed up for 5749 person-years. The
      cumulative incidence of second intracranial tumors and systemic malignancy was
      compared with population incidence rates through the Thames Cancer Registry and
      the National Health Service Central Register (previously OPCS) to record death
      and the potential causes. Eleven patients developed a second brain tumor,
      including five meningiomas, four high grade astrocytomas, one meningeal sarcoma,
      and one primitive neuroectodermal tumor. The cumulative risk of second brain
      tumors was 2.0% [95% confidence interval (CI), 0.9-4.4%] at 10 yr and 2.4% (95%
      CI, 1.2-5.0%) at 20 yr, measured from the date of radiotherapy. The relative risk
      of second brain tumor compared with the incidence in the normal population was
      10.5 (95% CI, 4.3-16.7). The relative risk was 7.0 for neuroepithelial and 24.3
      for meningeal tumors. The relative risks were 24.2 (95% CI, 4.8-43.5), 2.9 (95%
      CI, 0-8.5), and 28.6 (95% CI, 0.6-56.6) during the intervals 5-9, 10-19, and more
      than 20 yr after radiotherapy (four cases occurred >20 yr after treatment). There
      was no evidence of excess risk of second systemic malignancy. An additional 10-yr
      update confirmed our previous report of an increased risk of second brain tumors
      in patients with pituitary adenoma treated with surgery and radiotherapy. The
      2.4% risk at 20 yr remains low and should not preclude the use of radiotherapy as
      an effective treatment option. However, an increased risk of second brain tumors
      continues beyond 20 and 30 yr after treatment.

PMID- 15562022
TI  - Marked reutilization of free fatty acids during activated lipolysis in human
      skeletal muscle.
AB  - Release of glycerol and free fatty acids (FFA) was investigated in human skeletal
      muscle strips. In the basal state, glycerol and FFA were released at almost
      equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor
      agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol
      release, whereas FFA release was unaffected. Basal and isoprenaline-induced
      glycerol release correlated positively with the age of the donors (r = 0.5, P <
      0.005) but not with their body mass index (P > or = 0.4). Biochemical experiments
      with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in
      the cytosol and mitochondrial fraction and that it constituted the common long
      and active form of the protein. Electron microscopy studies in rat skeletal
      muscle using labeled highly specific HSL antibodies verified the cytosolic
      location of HSL and, furthermore, indicated an accumulation of HSL-adjoining
      mitochondria. These results suggest that FFA produced in myocytes during
      catecholamine-induced lipolysis are retained by the muscle and, therefore by
      inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by
      HSL located in the cytosol as well as near the mitochondria may facilitate
      mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases
      during aging and may be independent of total body fat.

PMID- 15562023
TI  - The common -866G/A polymorphism in the promoter region of the UCP-2 gene is
      associated with reduced risk of type 2 diabetes in Caucasians from Italy.
AB  - Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important
      role in linking obesity to type 2 diabetes (T2D). Previous studies of the role of
      the UCP2 promoter -866G/A single nucleotide polymorphisms (SNP) in T2D have given
      opposite results. We tested the distribution of the -866G/A SNP in 746 T2D
      patients and 327 healthy unrelated Caucasians from Italy. We also tested for an
      effect of the P12A variant of the peroxisomal proliferator-activated receptor
      gamma 2 (PPAR gamma 2) gene on diabetes risk given by the UCP2 SNP. Compared with
      -866G/G carriers, a progressively reduced (P = 0.01) risk of T2D was observed in 
      866G/A and -866A/A subjects, with the latter showing an approximately 50% risk
      reduction [odd ratio (OR), 0.51; 95% confidence interval (CI), 0.3-0.8; P =
      0.003]. Conversely, the -866G/G genotype was associated with increased risk (OR,
      1.31; 95% CI, 1.01-1.71). Overall, the population risk attributable to the UCP2 
      866G/G genotype was about 12%. After stratifying for the PPAR gamma 2
      polymorphism, the increased risk conferred by the UCP2 G/G genotype was still
      evident among P12/P12 homozygous subjects (n = 801; OR, 1.38; 95% CI, 1.04-1.83),
      but seemed to disappear among the X12/A12 subjects (i.e. P12/A12 heterozygous or
      A12/A12 homozygous subjects; n = 137; OR, 0.87; 95% CI, 0.40-1.91). Whether this
      apparent difference is entirely due to the different number of carriers of the
      two PPAR gamma 2 genotypes is a likely possibility that deserves deeper
      investigation. In conclusion, in our population, the -866G/A SNP is associated
      with T2D. Additional studies in larger samples are needed to investigate the
      possibility of a concomitant effect of modifier genes such as PPAR gamma 2.

PMID- 15562024
TI  - Progesterone increases tissue factor gene expression, procoagulant activity, and
      invasion in the breast cancer cell line ZR-75-1.
AB  - Progesterone in hormonal preparations increases the incidence of breast cancer.
      Tissue factor (TF), the initiator of the extrinsic coagulation pathway, is
      associated with metastasis in a wide variety of cancers. We demonstrate herein
      that TF mRNA and protein are up-regulated by progesterone in the breast cancer
      cell line ZR-75. Epidermal growth factor, also associated with increased breast
      cancer risk, did not regulate TF. The increase in TF is both rapid and transient;
      increasing after 6 h, reaching a maximum at 24 h, before decreasing to basal
      levels at 72 h. Sucrose gradient experiments demonstrated that TF is located in
      the heavy fraction of the plasma membrane, although caveolin-1 is not expressed
      in ZR-75. To understand the physiological implications of an increase in TF, we
      performed coagulation and invasion assays. An increase in TF corresponded to an
      increase in procoagulant activity. Furthermore, progesterone increased the
      invasion of ZR-75 cells through a matrigel, an effect that was blocked by an
      antibody against TF. Because TF expression is associated with an enhanced risk of
      metastasis, we postulate that the progesterone-dependent up-regulation of TF
      provides a survival advantage to burgeoning breast cancer cells and may
      contribute to the increased risk of cancer associated with combined hormone
      replacement therapy.

PMID- 15562025
TI  - Circulating activators of peroxisome proliferator-activated receptors are reduced
      in preeclamptic pregnancy.
AB  - We previously described activators of peroxisome proliferator-activated receptor
      gamma (PPAR gamma) in the serum of pregnant women. We have also characterized
      this activating component by using a hexane-extracted serum fraction to examine
      PPAR activator levels in normal and preeclamptic (PE) pregnancies. In this study
      we report that the pregnancy PPAR activator is present in similar concentrations
      in serum and plasma. We also found that the activating fractions from pregnancy
      sera stimulate not only PPAR gamma, but also PPAR alpha, and are capable of
      inhibiting the production of inflammatory cytokines, consistent with known PPAR
      ligands. In experiments comparing extracts from normal and PE patients, we found
      that extracts from women with severe PE showed a reduced level of PPAR activation
      compared with extracts from normal pregnant women. This reduction was more
      pronounced for PPAR gamma than PPAR alpha activation. Finally, this reduction in
      circulating PPAR activator was observed weeks and sometimes months before the
      clinical diagnosis of PE. Based on these results, we conclude that PPAR
      activation is reduced in preeclamptic pregnancy before the onset of maternal
      symptoms. We speculate that endogenous regulators of PPAR play a role in maternal
      metabolism and immune function in normal and pathological pregnancies.

PMID- 15562026
TI  - Heparin-binding epidermal growth factor and its receptors mediate decidualization
      and potentiate survival of human endometrial stromal cells.
AB  - Heparin-binding epidermal growth factor (HB-EGF) has pleiotropic biological
      functions in many tissues, including those of the female reproductive tract. It
      facilitates embryo development and mediates implantation and is thought to have a
      function in endometrial receptivity and maturation. The mature HB-EGF molecule
      manifests its activity as either a soluble factor (sol-HB-EGF) or a transmembrane
      precursor (tm-HB-EGF) and can bind two receptors, EGFR and ErbB4/HER4. In this
      study, we identify factors that modulate expression of HB-EGF, EGFR, and ErbB4 in
      endometrial stromal cells in vitro. We demonstrate that levels of sol- and tm-HB
      EGF, EGFR, and ErbB4 are increased by cAMP, a potent inducer of decidualization
      of the endometrial stroma. We also show that production of sol- and tm-HB-EGF is
      differentially modulated by TNF alpha and TGF beta. Our data suggest that HB-EGF
      has a function in endometrial maturation in mediating decidualization and
      attenuating TNF alpha- and TGF beta-induced apoptosis of endometrial stromal
      cells.

PMID- 15562027
TI  - Thyroid hormone receptor expression in the human hypothalamus and anterior
      pituitary.
AB  - In the present study, we describe for the first time the distribution of thyroid
      hormone receptor (TR) isoforms in the human postmortem hypothalamus and anterior
      pituitary using immunocytochemistry. We used a set of polyclonal antisera raised
      against the specific isoforms of the human TR. The distribution of TR alpha 1,
      alpha 2, beta 1, and beta 2 was studied in consecutive sections of six
      hypothalami and pituitaries. Staining intensity showed strong interindividual
      variation but was consistently present in the infundibular nucleus,
      paraventricular nucleus, and supraoptic nucleus. In addition, strong TR
      immunoreactivity was observed in the anterior pituitary. Neuropeptide Y and
      proopiomelanocortin mRNA-positive cells in the infundibular nucleus, which were
      studied in three other hypothalami, appeared not to express TRs, and thus, the
      neurons expressing TRs in the human mediobasal hypothalamus remain to be
      characterized.

PMID- 15562028
TI  - Fibroblast growth factor 7: an inhibitor of phosphate transport derived from
      oncogenic osteomalacia-causing tumors.
AB  - Oncogenic osteomalacia (OO), a tumor-associated phosphate-wasting syndrome,
      provides an opportunity to identify regulators of renal phosphate homeostasis. We
      established cultures from OO-associated tumors. Conditioned medium from these
      cultures inhibited phosphate uptake in renal tubular epithelial cells. We then
      compared RNA from tumor-derived cultures expressing inhibitory activity with RNA
      from tumor-derived cultures in which inhibitory activity was not evident and
      identified candidate mRNAs specifically expressed by cultures inhibiting renal
      phosphate transport. Testing of identified candidates revealed that one protein,
      fibroblast growth factor 7 (FGF7), was a potent and direct inhibitor of phosphate
      uptake in vitro. A neutralizing monoclonal antibody to FGF7 reversed FGF7
      dependent phosphate transport inhibition and inhibitory activity in conditioned
      medium from tumor cell cultures. Immunoassay revealed abundant FGF7 in inhibitory
      conditioned medium and minimal amounts in nonconditioned medium or conditioned
      medium with no phosphate transport inhibitory activity. Furthermore, only small
      amounts of FGF23 were present in inhibitory conditioned medium, comparable to
      concentrations found in conditioned medium with no phosphate transport inhibitory
      activity. Thus, FGF7 was specifically identified when selecting for in vitro
      phosphate transport inhibitory activity of tumor-derived cultures and was
      confirmed as a potent inhibitor of phosphate transport. Finally, FGF7 message was
      confirmed in PCR products of mRNA extracted from fragments of each tumor. Members
      of the FGF family (other than FGF23) are expressed by OO-associated tumors and
      may play a role in mediating this syndrome.

PMID- 15562029
TI  - Differential role of progesterone receptor isoforms in the transcriptional
      regulation of human gonadotropin-releasing hormone I (GnRH I) receptor, GnRH I,
      and GnRH II.
AB  - Hypothalamic GnRH is a decapeptide that plays a pivotal role in mammalian
      reproduction by stimulating the synthesis and secretion of gonadotropins via
      binding to the GnRH receptor on the pituitary gonadotropins. It is hypothesized
      that sex steroids may regulate GnRH I (a classical form of GnRH), GnRH II (a
      second form of GnRH), and GnRH I receptor (GnRHRI) at the transcriptional level
      in target tissues. Thus, in the present study a role for progesterone (P4) in the
      regulation of GnRH I, GnRH II, and GnRHRI was investigated using a human neuronal
      medulloblastoma cell line (TE671) as an in vitro model. The cells were
      transfected with human GnRHRI promoter-luciferase constructs, and promoter
      activities were analyzed after P4 treatment by luciferase and beta-galactosidase
      assay. The mRNA levels of GnRH I and GnRH II were analyzed by RT-PCR. Treatment
      of TE671 cells with P4 resulted in a decrease in GnRHRI promoter activity
      compared with the control level in a dose- and time-dependent manner. Cotreatment
      of these cells with RU486, an antagonist of P4, reversed P4-induced inhibition of
      GnRHRI promoter activity, suggesting that the P4 effect is mediated by P4
      receptor (PR). In the cells transfected with a full-length of PR A- or PR B
      expressing vector, overexpression of PR A increased the sensitivity toward P4 in
      an inhibition of GnRHRI promoter, whereas PR B increased transcriptional activity
      of GnRHRI promoter in the presence of P4. However, PR B itself did not act as a
      transcriptional activator of GnRHRI promoter. Because TE671 cells have been
      recently demonstrated to express and synthesize two forms of GnRHs, we also
      investigated the regulation of GnRH mRNAs by P4. In the present study, P4
      increased GnRH I mRNA levels in a time- and dose-dependent manner. This
      stimulatory effect of P4 in the regulation of GnRH I mRNAs was significantly
      attenuated by RU486, whereas no significant difference in the expression level of
      GnRH II was observed with P4 or RU496. Interestingly, although the expression
      level of PR B was low compared with that of PR A, P4 action on the GnRH I gene
      was mediated by PR B. In conclusion, these results indicate that P4 is a potent
      regulator of GnRHRI at the transcriptional level as well as GnRH I mRNA. This
      distinct effect of P4 on the GnRH system may be derived from different pathways
      through PR A or PR B.

PMID- 15562030
TI  - Neonatal lethal osteochondrodysplasia with low serum levels of alkaline
      phosphatase and osteocalcin.
AB  - Neonatal lethal skeletal dysplasias are rare and typically involve thoracic
      malformations and severe limb shortening. We report on a newborn boy manifesting
      an osteochondrodysplasia associated with fatal respiratory insufficiency who had
      normal lung volumes and extremity lengths. His disorder featured aberrant
      skeletal patterning and defective ossification including a severely osteopenic
      skull, apparent absence of clavicles, and clefting of the mandible and vertebrae.
      Serum alkaline phosphatase and osteocalcin levels were markedly low. Biochemical
      studies suggested parathyroid insufficiency probably from critical illness.
      Histopathology at autopsy excluded impaired mineralization of skeletal matrix,
      but endochondral bone formation appeared disorganized with growth plate
      clustering of chondrocytes in hypertrophic zones and in zones of provisional
      calcification. Parathyroid glands were not found. Despite features of two
      distinctive heritable entities, hypophosphatasia and cleidocranial dysplasia, the
      cumulative findings did not match either condition, and no mutations were found
      in either the tissue nonspecific ALP isoenzyme or core-binding factor genes,
      respectively, or in the genes encoding osteocalcin or the osteoblast
      transcription factor osterix. This patient could represent the extreme of
      cleidocranial dysplasia (a disorder not always associated with structural
      mutation in core-binding factor A1), but more likely he defines a unique
      osteochondrodysplasia disrupting both intramembranous and endochondral bone
      formation.

PMID- 15562031
TI  - Diabetes induces p66shc gene expression in human peripheral blood mononuclear
      cells: relationship to oxidative stress.
AB  - Oxidative stress plays a role in cardiovascular dysfunction. This is of interest
      in diabetes, a clinical condition characterized by oxidative stress and increased
      prevalence of cardiovascular disease. The role of p66(shc) in oxidative stress
      related response has been demonstrated by resistance to and reduction of
      oxidative stress and prolonged lifespan in p66(shc-/-) mice. In this study we
      assess p66(shc) gene expression in peripheral blood mononuclear cells (PBM) from
      type 2 diabetic patients and healthy subjects. The p66(shc) mRNA level was
      assessed using RT-PCR with two sets of primers mapping for different p66(shc)
      regions. p66(shc) is expressed in both monocytes and lymphocytes. The level of
      p66(shc) mRNA was significantly higher in type 2 diabetic patients compared with
      controls (0.38 +/- 0.07 densitometric units vs. 0.13 +/- 0.08; P < 0.0001). In
      addition, total plasma 8-isoprostane levels, a marker of oxidative stress, were
      higher in type 2 diabetics (0.72 +/- 0.04 ng/ml) than in normal subjects (0.43 +/
      0.04, P < 0.001) and were significantly correlated to the p66(shc) mRNA level in
      PBM from type 2 diabetics (r(2) = 0.47; P = 0.0284). In conclusion, diabetes
      induces p66(shc) gene expression in circulating PBM; this up-regulation in
      expression is significantly associated with markers of oxidative stress. p66(shc)
      gene expression in PBM may represent a useful tool to investigate the oxidative
      stress involved in the pathogenesis of long-term diabetic complications.

PMID- 15562032
TI  - Type I interferons modulate the expression of thyroid peroxidase, sodium/iodide
      symporter, and thyroglobulin genes in primary human thyrocyte cultures.
AB  - We evaluated in primary human thyrocyte cultures the effect of interferon (IFN)
      alpha and -beta on the expression of thyroid peroxidase (TPO), sodium/iodide
      symporter (NIS), and thyroglobulin (Tg) as well as T(4) release. Human thyrocyte
      cultures were carried out with fresh normal thyroid tissue. Gene and protein
      expression of Tg, TPO, and NIS were assessed by RT-PCR and Western blot analysis
      after 24, 48, and 72 h of treatment with TSH alone (10 mIU/ml) and in combination
      with IFN alpha or -beta (10(4) U/ml). IFN inhibited the TSH-stimulated gene
      expression of Tg, TPO, and NIS in a time-dependent manner without significant
      differences between IFN alpha and -beta. Moreover, the addition of both type I
      IFNs clearly reduced the TSH-stimulated protein expression of Tg, TPO, and NIS
      after 72 h of exposure. Finally, this down-regulation was associated with a
      reduction of T(4) release by almost 50%. In conclusion, our study shows that both
      IFN alpha and -beta down-regulate the TSH-stimulated expression of Tg, TPO, and
      NIS as well as T(4) release. Indeed, the development of hypothyroidism during
      type I IFN therapy may be related, at least in part, to an abnormal expression
      and function of key proteins involved in iodine uptake and organification.

PMID- 15562033
TI  - Circulating fatty acids, non-high density lipoprotein cholesterol, and insulin
      infused fat oxidation acutely influence whole body insulin sensitivity in
      nondiabetic men.
AB  - Circulating lipids and tissue lipid depots predict insulin sensitivity.
      Associations between fat oxidation and insulin sensitivity are variable. We
      examined whether circulating lipids and fat oxidation independently influence
      insulin sensitivity. We also examined interrelationships among circulating
      lipids, fat oxidation, and tissue lipid depots. Fifty-nine nondiabetic males
      (age, 45.4 +/- 2 yr; body mass index, 29.1 +/- 0.5 kg/m(2)) had fasting
      circulating nonesterified fatty acids (NEFAs) and lipids measured, euglycemic
      hyperinsulinemic clamp for whole body insulin sensitivity [glucose infusion rate
      (GIR)], substrate oxidation, body composition (determined by dual energy x-ray
      absorptiometry), and skeletal muscle triglyceride (SMT) measurements. GIR
      inversely correlated with fasting NEFAs (r = -0.47; P = 0.0002), insulin-infused
      NEFAs (n = 38; r = -0.62; P < 0.0001), low-density lipoprotein cholesterol (r = 
      0.50; P < 0.0001), non-high-density lipoprotein cholesterol (r = -0.52; P <
      0.0001), basal fat oxidation (r = -0.32; P = 0.03), insulin-infused fat oxidation
      (r = -0.40; P = 0.02), SMT (r = -0.28; P < 0.05), and central fat (percentage; r
      = -0.59; P < 0.0001). NEFA levels correlated with central fat, but not with total
      body fat or SMT. Multiple regression analysis showed non-high-density lipoprotein
      cholesterol, fasting NEFAs, insulin-infused fat oxidation, and central fat to
      independently predict GIR, accounting for approximately 60% of the variance.
      Circulating fatty acids, although closely correlated with central fat,
      independently predict insulin sensitivity. Insulin-infused fat oxidation
      independently predicts insulin sensitivity across a wide range of adiposity.
      Therefore, lipolytic regulation as well as amount of central fat are important in
      modulating insulin sensitivity.

PMID- 15562034
TI  - Insulin resistance is associated with impaired nitric oxide synthase activity in
      skeletal muscle of type 2 diabetic subjects.
AB  - Type 2 diabetes is an insulin-resistant state characterized by hyperinsulinemia
      and accelerated atherosclerosis. In vitro and in vivo studies in rodents have
      suggested that nitric oxide generation plays an important role in glucose
      transport and insulin action. We determined nitric oxide synthase (NOS) activity
      in skeletal muscle of 10 type 2 diabetic (hemoglobin A(1C) = 6.8 +/- 0.1%) and 11
      control subjects under basal conditions and during an 80 mU/m(2).min euglycemic
      insulin clamp performed with vastus lateralis muscle biopsies before and after 4
      h of insulin. In diabetics, insulin-stimulated glucose disposal (Rd) was reduced
      by 50%, compared with controls (5.4 +/- 0.3 vs. 10.4 +/- 0.5 mg/kg.min, P <
      0.01). Basal NOS activity was markedly reduced in the diabetic group (101 +/- 33
      vs. 457 +/- 164 pmol/min.mg protein, P < 0.05). In response to insulin, NOS
      activity increased 2.5-fold in controls after 4 h (934 +/- 282 pmol/min.mg
      protein, P < 0.05 vs. basal), whereas insulin failed to stimulate NOS activity in
      diabetics (86 +/- 28 pmol/min.mg protein, P = NS from basal). Basal NOS protein
      content in muscle was similar in controls and diabetics and did not change
      following insulin. In controls, insulin-stimulated NOS activity correlated
      inversely with fasting plasma insulin concentration (r = -0.58, P = 0.05) and
      positively with Rd (r = 0.71, P = 0.03). In control and diabetic groups
      collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.52, P =
      0.02). We conclude that basal and insulin-stimulated muscle NOS activity is
      impaired in well-controlled type 2 diabetic subjects, and the defect in insulin
      stimulated NOS activity correlates closely with the severity of insulin
      resistance. These results suggest that impaired NOS activity may play an
      important role in the insulin resistance in type 2 diabetic individuals.

PMID- 15562035
TI  - Pacemaker misinformation in the perioperative period: programming around the
      problem.

PMID- 15562036
TI  - Percutaneous radiofrequency trigeminal rhizotomy in a patient with an implanted
      cardiac pacemaker.
AB  - Percutaneous radiofrequency ablation is a frequently used treatment for
      trigeminal neuralgia. Radiofrequency is another potential source of
      electromagnetic interference to implanted cardiac pacemakers. Our patient had a
      permanent pacemaker and underwent the procedure without incident.

PMID- 15562037
TI  - The effect of dilution on plasma coagulation kinetics determined by
      thrombelastography is dependent on antithrombin activity and mode of activation.
AB  - Hemodilution-associated hypercoagulability has been the focus of several
      investigations because significant morbidity and mortality have been associated
      with perioperative thrombophilia. Because most investigations implicate
      imbalances in procoagulant/anticoagulant activity as the etiology of hemodilution
      associated hypercoagulability, we determined the effects of dilution on
      coagulation kinetics and clot strength with thrombelastography (TEG(R)). Control
      plasma (+/-celite activation) and antithrombin (AT)-deficient (<10% activity)
      plasma were diluted 0%, 10%, 20%, and 30% with saline. TEG(R) variables measured
      included time to clot initiation (reaction time, R), speed of clot propagation
      (angle, alpha), and clot strength (amplitude, A; or shear elastic modulus, G).
      Dilution of control plasma (10%-30%) resulted in a significant (P < 0.05) 16%
      decrease in R values, no change in alpha values, and decrease in A and G values.
      AT-deficient plasma had significantly smaller R values compared with control, and
      dilution did not change R values in AT-deficient plasma. Celite activation
      eliminated dilution-associated changes in R values in control plasma but resulted
      in linear decreases (R(2) = 0.88-0.96, P < 0.0001) in alpha, A, and G in response
      to dilution. Thus, our data indirectly support the concept that decreases in AT
      activity cause dilution-mediated hypercoagulability in plasma. Finally, celite
      activation permits quantification of dilution with TEG.

PMID- 15562038
TI  - The effect of hemopure on coagulation in clinically relevant concentrations.
AB  - Hemopure is a new colloidal blood substitute that may influence coagulation. We
      designed this study to examine the influence of this product on in vitro
      coagulation of whole blood by using the thrombelastograph (TEG). Blood samples
      from 20 volunteers were obtained. Hemopure was added to blood samples to obtain
      0.5, 1, and 2 g/dL mixtures of Hemopure in blood. Control consisted of an
      undiluted sample and, for comparison, two samples diluted with volumes of
      lactated Ringer's solution (LR) equivalent to the two higher Hemopure dilutions.
      TEG with Hemopure at a concentration of 2 g/dL showed significantly shorter
      reaction and clot formation k times and an increased alpha angle compared with
      control. LR dilution with equivalent volume to 2 g/dL Hemopure solution also
      resulted in significantly shorter reaction and k times, as well as an increased
      alpha angle. Coagulation in samples with Hemopure at concentrations of 0.5 and 1
      mg/dL did not vary significantly from control. Maximum amplitude did not vary
      significantly from control in any samples. The effect of Hemopure on TEG measures
      of coagulation is not significantly different from that of LR at clinically
      relevant concentrations.

PMID- 15562039
TI  - The response to activated protein C after cardiopulmonary bypass: impact of
      factor V leiden.
AB  - Activated protein C (aPC) resistance is a recognized hypercoagulable phenotype
      that is associated with increased risk for thrombosis in multiple clinical
      settings. Factor V Leiden (FVL) represents a specific inherited cause of aPC
      resistance, but the perioperative thrombotic risk of FVL is unclear. In this
      investigation, we sought to quantify whether cardiopulmonary bypass produces
      alterations in aPC resistance in FVL carriers and noncarrier controls, testing
      the hypothesis that FVL is associated with a relatively hypercoagulable
      postoperative state. Two-hundred-five adult cardiac surgery patients were
      prospectively enrolled into a genetic registry whose purpose was to study the
      impact of genetic variables on clinical outcomes. For this study, 8 subjects
      heterozygous for FVL were identified (group L), as well as 2 control groups:
      group MC, matched controls, 18 matched subjects without FVL; and group UC,
      unmatched controls, 11 consecutive subjects without FVL. Plasma was sampled at
      the beginning of surgery, 10 min after protamine administration, and on
      postoperative day 1, and assayed for resistance to aPC (normal aPC ratio is
      >2.0). Both MC and UC groups exhibited normal aPC ratio at baseline (2.40 and
      2.36, respectively), which increased significantly (to 2.76 and 2.75, P = 0.007
      and 0.021, respectively) on postoperative day 1, indicating increased
      postoperative sensitivity to aPC. Conversely, group L subjects exhibited aPC
      resistance at baseline (aPC ratio 1.80), and did not change significantly
      postoperatively (P = 0.867). Patients without FVL therefore show laboratory
      evidence consistent with relative protection from postoperative thrombosis,
      whereas FVL carriers do not. These findings provide mechanistic support for
      previous speculations of increased postoperative thrombotic risk associated with
      FVL.

PMID- 15562040
TI  - Fenoldopam mesylate and renal function in patients undergoing liver
      transplantation: a randomized, controlled pilot trial.
AB  - To test the relative effects on serum creatinine (CRE), blood urea nitrogen
      (BUN), and urine output of small-dose dopamine and fenoldopam in patients
      undergoing liver transplantation, we randomized 43 patients to 1 of 2 continuous
      infusions over 48 h, starting with anesthesia induction: fenoldopam, 0.1 microg .
      kg(-1) . min(-1) or dopamine, 2 microg . kg(-1) . min(-1). We used predetermined
      hemodynamic and intravascular volume goals (intrathoracic blood volume index 800
      1000 mL/m(2), extravascular lung water index <7 mL/kg) to manage patients with an
      algorithm for use of mannitol and furosemide to maintain urine output >1 mL . kg(
      1) . h(-1). At postoperative day 3, the median CRE increase was 0.2 mg/dL
      (interquartile range [IQR] -0.2-0.5) with fenoldopam and 0.5 mg/dL (IQR 0.3-0.9,
      P = 0.004) in the dopamine group. The BUN increase was median 2 mg/dL (IQR -2-8)
      versus 8.5 mg/dL (IQR 5-12, P = 0.01), respectively, with fenoldopam versus
      dopamine. Urine output was similar; however, significantly fewer fenoldopam
      patients required furosemide compared with dopamine patients (median 1 [IQR 0-3]
      versus 3 [IQR 2-4], respectively, P = 0.003). The hemodynamic effects of dopamine
      and fenoldopam were similar. Compared with dopamine, in the setting of liver
      transplantation, fenoldopam is associated with better CRE and BUN values.

PMID- 15562041
TI  - Bronchoscopic lung volume reduction in patients with severe emphysema: anesthetic
      management.
AB  - Bronchoscopic lung volume reduction is a novel approach to the treatment of
      severe emphysema. Its objective is to achieve the same improvements in lung
      function and exercise tolerance as lung volume reduction surgery while avoiding
      the surgical morbidity and mortality. We describe the anesthetic experience in a
      series of seven patients who underwent a total of eight procedures (one patient
      underwent a second procedure on the contralateral side). The technique used was
      one of total IV anesthesia using remifentanil and propofol, with a ventilatory
      strategy aimed at avoiding gas trapping and dynamic hyperinflation. To achieve
      this pressure, limited ventilation with a prolonged expiratory phase was provided
      by a Draeger Evita 2 ventilator. This technique resulted in intraoperative
      hypercapnia (Paco(2) 6.75 kPa) compared with baseline values (median Paco(2) 5.1
      kPa; P < 0.05), but 2 h postoperatively the arterial partial pressure of CO(2)
      was returning to baseline (median Paco(2) 5.6 kPa; P < 0.01 compared with
      intraoperative data). There were no deaths or admissions to the intensive care
      unit after the procedure. One patient developed a pneumothorax that required
      drainage, three patients had acute exacerbations of chronic obstructive pulmonary
      disease, and one patient developed a cough that resolved spontaneously. Total
      hospital stay did not exceed 5 days for any of these patients.

PMID- 15562042
TI  - The effects of halothane, isoflurane, and sevoflurane on Ca2+ current and
      transient outward K+ current in subendocardial and subepicardial myocytes from
      the rat left ventricle.
AB  - Halothane, isoflurane, and sevoflurane abbreviate ventricular action potential
      duration (APD), and for halothane this effect is greater in the subendocardium
      than in the subepicardium. In this study we investigated mechanisms underlying
      the regional effects of these anesthetics on APD. The effect of 0.6 mM halothane,
      isoflurane, and sevoflurane on the action potential, L-type Ca(2+) current,
      transient outward K(+) current (I(to)), and steady-state current was recorded in
      rat left ventricular subendocardial and subepicardial myocytes. Halothane and
      isoflurane (but not sevoflurane) reduced APD significantly (P < 0.05), more in
      subendocardial than subepicardial myocytes. Peak L-type Ca(2+) current did not
      differ between regions and, compared with control, was reduced significantly in
      both regions by 40% (P < 0.001), 20% (P < 0.001), and 12% (P < 0.01) by
      halothane, isoflurane, and sevoflurane, respectively. I(to) was greater in
      subepicardial (3.95 +/- 0.29 nA) than subendocardial (1.12 +/- 0.05 nA) myocytes.
      In subepicardial myocytes, peak I(to) was reduced significantly by halothane (P <
      0.01) and isoflurane (P < 0.05) (by 8% and 7%, respectively) but was unaffected
      by sevoflurane. No significant reduction of I(to) was observed in subendocardial
      myocytes with the three anesthetics. The steady-state current was increased
      significantly (P < 0.05), but the extent of this increase did not differ between
      the two regions or among the three anesthetics. Therefore, greater inhibition of
      I(to) in subepicardial than subendocardial myocytes by halothane and isoflurane
      could underlie their transmural effects on APD.

PMID- 15562043
TI  - Transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion
      related mortality. It is characterized by injury to the alveolar-capillary
      membrane precipitated by transfusion factors, antibodies, and/or inflammatory
      mediators, in a susceptible host. In the absence of a specific test, TRALI is
      defined clinically as a syndrome of acute lung injury that develops during or
      within 6 h of transfusion. The absence of left atrial hypertension and large
      protein content of edema fluid may help differentiate TRALI from hydrostatic
      pulmonary edema. The treatment is supportive. The blood bank needs to be notified
      promptly so that an appropriate workup and prevention are initiated in a timely
      manner.

PMID- 15562044
TI  - The anterior jugular venous system: variability and clinical impact.
AB  - The anterior jugular venous system, with its interconnections to the subclavian
      and deep jugular veins, provides a collateral venous network across the midline
      of the neck area, which is especially important in unilateral occlusion of an
      innominate vein. We illustrate the variability of this system and its clinical
      impact on catheterization by three cases of landmark-guided central venous
      cannulation. Case 1: Cannulation of the left internal jugular vein with a central
      venous catheter and of the left innominate vein (LIV) with a pulmonary artery
      catheter resulted in correctly positioned catheter tips. However, these catheters
      were actually not placed in the innominate vein but coursed through the jugular
      venous arch. Case 2: Cannulation of the left subclavian vein was complicated by
      resistance of guidewire advancement at 13 cm. Occlusion of the LIV and
      enlargement of the jugular venous arch were present. Case 3: Insertion of a
      pulmonary artery catheter and a central venous catheter through the LIV. The
      pulmonary artery catheter was correctly placed. The tip of the central venous
      catheter was mistakenly positioned in the left anterior jugular vein. We describe
      the normal anatomy of the anterior jugular venous system and its role as a major
      collateral. Correct placement of central venous catheters may be possible via the
      anterior jugular venous system. Conversely, central venous catheters
      malpositioned in the anterior jugular vein can increase the risk for
      complications and should be removed.

PMID- 15562045
TI  - The development and validation of a risk score to predict the probability of
      postoperative vomiting in pediatric patients.
AB  - Risk scores to predict the occurrence of postoperative vomiting (PV) or nausea
      and vomiting that were developed for adult patients do not fit for children,
      because several risk factors are difficult to assess or are usually not
      applicable in pediatric patients (e.g., smoking status). Thus, in the present
      study, we sought to develop and to validate a simple score to predict PV in
      children (POVOC-score). Development and validation of the new score was based on
      data from 4 independent institutions of 1257 children (aged 0-14 yr) undergoing
      various types of surgery under general anesthesia without antiemetic prophylaxis.
      Preoperatively, several potential risk factors were recorded. Postoperatively,
      the occurrence of PV was observed for up to 24 h. The dataset was randomly split
      into an evaluation set (n = 657) that was analyzed using a forward logistic
      regression technique and a validation set (n = 600) that was used to confirm the
      accuracy of prediction by means of the area under a receiver operating
      characteristic curve. Four independent risk factors for PV were identified in the
      final analysis: duration of surgery >/=30 min, age >/=3 yr, strabismus surgery,
      and a positive history of PV in the children or PV/postoperative nausea and
      vomiting in relatives (mother, father, or siblings). The incidence of PV was 9%,
      10%, 30%, 55%, and 70% for 0, 1, 2, 3, and 4 risk factors observed. Using these
      incidences as cut-off values in the validation dataset, the area under the
      receiver operating characteristic curve was 0.72 (95% confidence interval: 0.68
      0.77). Our data suggest that PV can be predicted with an acceptable accuracy
      using a four-item simplified risk score.

PMID- 15562046
TI  - The effects of chin lift and jaw thrust while in the lateral position on stridor
      score in anesthetized children with adenotonsillar hypertrophy.
AB  - Obstruction of the upper airway is a major challenge for anesthesiologists
      administering general anesthesia in spontaneously breathing patients, especially
      in pediatric anesthesia with adenotonsillar hypertrophy. Lateral positioning is a
      simple treatment for obstructive sleep apnea and also decreases collapsibility of
      the pharynx in anesthetized adults with obstructive sleep apnea. In this study,
      we examined the effects of body position shifting and common airway maneuvers,
      such as chin lift and jaw thrust, on airway patency (stridor score) in
      anesthetized children scheduled for adenotonsillectomy. Thirty children aged 1-10
      yr were anesthetized with sevoflurane. During spontaneous breathing of 5%
      sevoflurane, stridor score was recorded. After baseline recording, chin lift and
      jaw thrust were performed on patients in both the supine and the lateral
      decubitus positions. Chin lift and jaw thrust improved the stridor score.
      Furthermore, lateral positioning dramatically enhanced the effects of these
      airway maneuvers on airway patency. Jaw thrust combined with lateral positioning
      provided easy airway management for the anesthesiologists. We conclude that
      lateral positioning combined with airway maneuvers significantly improved airway
      patency compared with the airway maneuvers alone for patients in the supine
      position.

PMID- 15562047
TI  - An evaluation of a noninvasive cardiac output measurement using partial carbon
      dioxide rebreathing in children.
AB  - Cardiac output (CO) is an important hemodynamic measure that helps to guide the
      therapy of critically ill patients. Invasive CO assessment in infants and
      children is often avoided because of the inherent risks. A noninvasive CO monitor
      that uses partial rebreathing has been recently developed to determine CO via the
      Fick principle for carbon dioxide. There have been no clinical studies confirming
      its accuracy in pediatric patients. This is a prospective observational study of
      37 children <12 yr of age who underwent cardiac catheterization. Under general
      anesthesia via an endotracheal tube without a leak, we made multiple CO
      measurements using thermodilution and compared them with noninvasively determined
      CO measurements. Paired measurements were analyzed for bias, precision, and
      correlation via Bland-Altman plot and linear regression. Noninvasive measurements
      showed a linear correlation with thermodilution CO assessment with an r value of
      0.83 (P < 0.03). Bland-Altman analysis yielded a bias of -0.27 L/min and a
      precision +/-1.49 L/min. Cardiac index measurements demonstrated a decreased r
      value of 0.67 (P = 0.15) and a bias of -0.18 L . min(-1) . m(-2) and precision of
      +/-2.13 L . min(-1) . m(-2). Differences between partial rebreathing measurements
      and thermodilution measurements were largest in children with a body surface area
      of </=0.6 m(2) ventilated with tidal volumes <300 mL. Based on these findings,
      noninvasive CO measurement using partial rebreathing may be clinically acceptable
      in children with >0.6 m(2) body surface area and >300 mL tidal volume.

PMID- 15562048
TI  - Preoperative anxiety and emergence delirium and postoperative maladaptive
      behaviors.
AB  - Based on previous studies, we hypothesized that the clinical phenomena of
      preoperative anxiety, emergence delirium, and postoperative maladaptive
      behavioral changes were closely related. We examined this issue using data
      obtained by our laboratory over the past 6 years. Only children who underwent
      surgery and general anesthesia using sevoflurane/O(2)/N(2)O and who did not
      receive midazolam were recruited. Children's anxiety was assessed preoperatively
      with the modified Yale Preoperative Anxiety Scale (mYPAS), emergence delirium was
      assessed in the postanesthesia care unit, and behavioral changes were assessed
      with the Post Hospital Behavior Questionnaire (PHBQ) on postoperative days 1, 2,
      3, 7, and 14. Regression analysis showed that the odds of having marked symptoms
      of emergence delirium increased by 10% for each increment of 10 points in the
      child's state anxiety score (mYPAS). The odds ratio of having new-onset
      postoperative maladaptive behavior changes was 1.43 for children with marked
      emergence status as compared with children with no symptoms of emergence
      delirium. A 10-point increase in state anxiety scores led to a 12.5% increase in
      the odds that the child would have a new-onset maladaptive behavioral change
      after the surgery. This finding is highly significant to practicing clinicians,
      who can now predict the development of adverse postoperative phenomena, such as
      emergence delirium and postoperative behavioral changes, based on levels of
      preoperative anxiety.

PMID- 15562049
TI  - A model for educational simulation of infant cardiovascular physiology.
AB  - Full-body patient simulators provide the technology and the environment necessary
      for excellent clinical education while eliminating risk to the patient. The
      extension of simulator-based training into management of basic and critical
      situations in complex patient populations is natural. We describe the derivation
      of an infant cardiovascular model through the redefinition of a complete set of
      parameters for an existing adult model. Specifically, we document a stepwise
      parameter estimation process, explicit simplifying assumptions, and sources for
      these parameters. The simulated vital signs are within the target hemodynamic
      variables, and the simulated systemic arterial pressure wave form and left
      ventricular pressure volume loop are realistic. The system reacts appropriately
      to blood loss, and incorporation of aortic stenosis is straightforward. This
      infant cardiovascular model can form the basis for screen-based educational
      simulations. The model is also an essential step in attaining a full-body, model
      driven infant simulator.

PMID- 15562050
TI  - Anesthetic concerns for robot-assisted laparoscopy in an infant.
AB  - A 2-mo-old infant with biliary atresia was scheduled for laparoscopic Kasai with
      robot assistance. Before surgery, a practice trial maneuvering the cumbersome
      robotic equipment was performed to ensure rapid access to the patient in case of
      emergency. IV access, tracheal intubation, and arterial line placement followed
      inhaled anesthesia induction with sevoflurane. Robotic setup took 53 min and
      severely limited patient access. No adverse events occurred during the procedure
      requiring the removal of the robotic equipment, and the patient was discharged
      after a stable postoperative recovery. Advance preparation is required to
      maximize patient safety during robotic surgery.

PMID- 15562051
TI  - A comparison of selective spinal anesthesia with hyperbaric bupivacaine and
      general anesthesia with desflurane for outpatient knee arthroscopy.
AB  - In this randomized and controlled trial, 64 adult ambulatory knee arthroscopy
      patients received either selective spinal anesthesia (SSA) with 4 mg of
      hyperbaric bupivacaine or general anesthesia (GA) with desflurane. We conducted
      the study to determine whether SSA with small-dose bupivacaine provides equal
      fast-tracking possibilities, a shorter stay in the postanesthesia care unit, and
      earlier discharge home compared with GA with desflurane. Patients with a high
      risk for postoperative nausea and vomiting received prophylaxis in the GA group.
      No difference was seen in the fast-tracking possibilities or time in the
      postanesthesia care unit between the groups. Home readiness was achieved after
      114 (31-174) and 129 (28-245) min (NS) in the SSA and GA groups, respectively. In
      the hospital, the pain scores were significantly (P < 0.001) lower in the SSA
      group compared with the GA group and the need for postoperative opioids was
      significantly (P = 0.008) larger after GA. The incidence of postoperative nausea
      and vomiting was 0% versus 19% in the SSA and GA groups (P = 0.024),
      respectively. We conclude that for outpatients undergoing knee arthroscopy, SSA
      with hyperbaric bupivacaine provides equal recovery times with less frequent side
      effects compared with GA with desflurane.

PMID- 15562052
TI  - Postoperative confusion increases in elderly long-term benzodiazepine users.
AB  - We investigated the relationship between postoperative confusion and duration of
      benzodiazepine exposure, preoperative anxiety, depressive state, and cognitive
      function in elderly patients regularly taking benzodiazepines. We studied 328
      patients ranging in age from 65 to 80 yr who underwent orthopedic surgery.
      Information on benzodiazepine use was obtained by face-to-face interview and
      visual assessment of the patient's medicine chest. Postoperative confusion was
      assessed by using a confusion-assessment method. The patients were divided into
      two groups: those who regularly took benzodiazepines and those who did not. Fifty
      seven (17%) of 328 patients were treated with benzodiazepines. There were no
      significant differences in preoperative Mini-Mental State (MMS) scores, anxiety
      scores, or depression scores between benzodiazepine users and nonusers.
      Postoperative confusion occurred in 15 (26%) of 57 benzodiazepine users and in 34
      (13%) of 271 nonusers (P < 0.01). The patients who had a score <23 on the MMS
      were 5 (9%) of 57 benzodiazepine users and 8 (3%) of 271 nonusers (P < 0.05).
      Postoperative confusion occurred in 13 (35%) of 37 long-term benzodiazepine users
      (daily use for >1 yr) and in 2 (10%) of 20 short-term users (daily use for <1
      yr). The incidence of postoperative confusion was significantly more frequent in
      long-term than in short-term benzodiazepine users or nonusers of benzodiazepines.
      The patients who developed a score <23 on the MMS were 5 (14%) of 37 long-term
      benzodiazepine users and 0 (0%) of 20 short-term benzodiazepine users. In
      conclusion, the incidence of postoperative confusion was significantly more
      frequent in long-term benzodiazepine users.

PMID- 15562053
TI  - The postoperative blood-sparing efficacy of oral versus intravenous tranexamic
      acid after total knee replacement.
AB  - To assess the blood-sparing efficacy of tranexamic acid (TA) administered orally
      or via a variable IV infusion, 80 healthy patients undergoing elective total knee
      replacement were studied according to a prospective, controlled, randomized,
      single-blinded study design. Patients were allocated to one of four treatment
      groups. In group TA-long, 30 min before deflation of the limb tourniquet, an IV
      bolus dose of TA 15 mg/kg was administered over 30 min. Thereafter, a constant IV
      infusion of 10 mg . kg(-1) . h(-1) was administered until 12 h after final
      deflation of the limb tourniquet. In group TA-short, a similar regimen was
      followed; however, the constant IV infusion was discontinued 2 h after final
      deflation of the limb tourniquet (time of discharge from the postanesthesia care
      unit). Thereafter, oral TA 1 g was administered after 6 and 12 h. In group TA
      oral, 60 min before surgery an oral dose of TA 1 g was administered. After
      surgery, a similar dose of TA was administered every 6 h for the next 18 h. In
      the control group, TA was not administered. At patient discharge, postoperative
      allogeneic blood administration was significantly more in group Control when
      compared with each of the three TA treatment groups. Because oral drug
      administration is simple and does not require specific infusion equipment, the
      authors suggest that oral TA is a superior blood-sparing strategy compared with
      IV drug administration.

PMID- 15562054
TI  - The effect of epidural bupivacaine on induction and maintenance doses of propofol
      (evaluated by bispectral index) and maintenance doses of fentanyl and vecuronium.
AB  - The growing interest in combining local and general anesthesia has led to studies
      investigating possible interactions between general anesthesia and local
      anesthetics administered via spinal, epidural, IV, or IM routes. However, no
      study has evaluated the effect of local anesthetics on all three components of
      balanced anesthesia, i.e., hypnosis, analgesia, and muscle relaxation. In this
      prospective, randomized, double-blind study, we investigated the effect of
      epidural bupivacaine on the dose requirement of propofol (as evaluated by using
      the bispectral index [BIS]), fentanyl, and vecuronium for general anesthesia.
      This study consisted of 30 adults, ASA physical status I and II, undergoing
      Whipple's pancreaticoduodenectomy for periampullary carcinoma lasting >4 h. An
      epidural catheter was placed between T9-10. Depending on the group allocation, 10
      mL of the study drug was administered as a bolus followed by an infusion at 6
      mL/h via the epidural catheter. Patients were divided into 2 groups of 15 each.
      Patients in the control group received epidural normal saline whereas those in
      the bupivacaine group received epidural bupivacaine 0.1%. Induction of anesthesia
      was performed with IV fentanyl 2 mug/kg and propofol titrated to achieve BIS
      between 40-50. Endotracheal intubation was facilitated by the IV administration
      of vecuronium 0.1 mg/kg and patient's lungs were ventilated with 66% nitrous
      oxide in oxygen. After intubation, infusion of propofol 1% was titrated to
      maintain BIS between 40-50. Inadequate analgesia was defined as an increase in
      systolic blood pressure and/or heart rate by >20% of baseline values in response
      to surgical stimulus and was treated with bolus fentanyl 0.5 mug/kg.
      Neuromuscular monitoring was used to assess the need for additional doses of
      vecuronium. Data were analyzed by using the Student's t-test and P </= 0.05 was
      considered significant. The requirement of propofol for induction and maintenance
      of anesthesia in the bupivacaine group was 1.3 +/- 0.3 mg/kg and 2.4 +/- 0.9 mg .
      kg(-1) . h(-1), respectively, compared with 2.4 +/- 0.6 mg/kg and 4.4 +/- 1.6 mg
      . kg(-1) . h(-1) observed in the control group (P < 0.05). Significant reduction
      was also observed in the requirement of vecuronium and fentanyl during
      maintenance in the bupivacaine group (P < 0.05). We conclude that epidural
      bupivacaine given before induction of anesthesia reduces the requirement of
      propofol, fentanyl, and vecuronium during general anesthesia.

PMID- 15562055
TI  - The inotropic and lusitropic effects of ketamine in isolated human atrial
      myocardium: the effect of adrenoceptor blockade.
AB  - We studied the direct myocardial effects of racemic ketamine, in the presence of
      alpha- and beta-adrenoceptor blockade, on isolated human right atrial myocardium.
      Isometric force of contraction (FoC), its first derivative with time (+dF/dt),
      the contraction relaxation coupling parameter R2 = (+dF/dt) / (-dF/dt), and time
      to half relaxation (T(1/2)) were recorded before and after addition of 10(-6),
      10(-5) and 10(-4) M racemic ketamine alone and in the presence of alpha
      adrenoceptor blockade (phentolamine 10(-6) M) and beta-adrenoceptor blockade
      (propranolol at 10(-6) M). Ketamine had a moderate positive inotropic effect at
      10(-5) M (FoC, 104% +/- 5% of baseline value; P = 0.03) and 10(-4) M (FoC, 107%
      +/- 11% of baseline value; P = 0.09). Racemic ketamine had a negative inotropic
      effect in the presence of propranolol (FoC, ketamine 10(-6) M, 77% +/- 11%;
      ketamine 10(-5) M, 63% +/- 16%; ketamine 10(-4) M, 62% +/- 17% of baseline; P <
      0.001) but not phentolamine (FoC, ketamine at 10(-6) M, 94% +/- 6%; ketamine 10(
      5) M, 96% +/- 5%; and ketamine 10(-4) M, 98% +/- 15% of baseline). Ketamine
      decreased T(1/2) (ketamine 10(-5) M, 94% +/- 3% of baseline value; P < 0.001 and
      ketamine 10(-4) M, 90% +/- 9% of baseline value; P = 0.007) but did not modify
      R2. In human right atrial myocardium, racemic ketamine induced a moderate
      positive inotropic effect and hastened isometric relaxation. In the presence of
      beta-adrenoceptor blockade it induced a direct negative inotropic effect.

PMID- 15562056
TI  - Intravenous lidocaine suppresses fentanyl-induced coughing: a double-blind,
      prospective, randomized placebo-controlled study.
AB  - IV lidocaine is effective in suppressing the cough reflex of tracheal intubation,
      extubation, bronchography, bronchoscopy, and laryngoscopy. We investigated this
      effect of lidocaine on fentanyl-induced cough in 502 patients of ASA physical
      status I and II scheduled for elective surgery. The patients were assigned to 2
      equal groups to receive either lidocaine 1.5 mg/kg or placebo (0.9% saline) over
      5 s 1 min before the administration of fentanyl 3 mug/kg in a randomized and
      double-blind fashion. Coughs were classified as coughing and graded as mild (1
      2), moderate (3-4), or severe (5 or more). The results of the study suggest that
      IV lidocaine 1.5 mg/kg, when administered 1 min before fentanyl, is significantly
      effective in suppressing fentanyl-induced cough compared to placebo (0.9% saline)
      (218 versus 165 patients) (P < 0.002) but without affecting the severity of cough
      (P > 0.05).

PMID- 15562057
TI  - Pain on injection: a double-blind comparison of propofol with lidocaine
      pretreatment versus propofol formulated with long- and medium-chain
      triglycerides.
AB  - The incidence of pain on injection of propofol has been reported to be 70%. A new
      propofol formulation with a 10% emulsion of long- and medium-chain triglycerides
      (LCT/MCT) is associated with less pain on injection. Our goal was to compare the
      effect of propofol-LCT/MCT on the incidence of pain versus propofol with
      lidocaine 40 mg IV pretreatment injected as a Bier's block. Two hundred healthy
      women scheduled for ambulatory gynecological procedures were allocated to 1 of 2
      groups in a randomized double-blind fashion. Group LIDO received lidocaine 2% 2
      mL injected with a tourniquet 1 min before propofol 1% 2 mg/kg IV; group LCT/MCT
      received NaCl 0.9% 2 mL with tourniquet 1 min before propofol-LCT/MCT 1% 2 mg/kg
      IV. Spontaneous verbal expressions of pain, movement of hand, frowning, and
      moaning during the injection were recorded. The incidence and severity of pain
      were assessed 30 min and 6 h after surgery. Recall of pain was considered with a
      visual analog scale (VAS) score >1, and pain was graded as VAS 0-10. More women
      reported spontaneous verbal expression of pain with propofol-LCT/MCT (47% versus
      24%; P = 0.0014; relative risk 1.61 [95% confidence interval, 1.22-2.13]). Among
      women with a painful injection, there was no difference after surgery regarding
      the intensity of pain or recall of pain. In contrast to previous reports, we
      found that propofol-LCT/MCT resulted in a more frequent incidence of pain than
      propofol 1% with IV lidocaine pretreatment. This may be due to the diversity of
      pain definitions used in studies or to the lack of premedication in our study.

PMID- 15562058
TI  - The hemodynamic effects of ephedrine on the onset time of rocuronium in pigs.
AB  - Several studies have found a correlation between the onset time of muscle
      relaxants, cardiac index, and muscle blood flow. Ephedrine increases these
      hemodynamic variables and shortens onset time of rocuronium in humans. Our aim in
      this animal study was to determine the effect of ephedrine on the onset time of
      rocuronium, cardiac index, and muscle blood flow after administration of
      thiopental. At predefined measuring points, mean arterial blood pressure and
      cardiac index were measured invasively and onset time was determined
      mechanomyographically. Twenty-four pigs were randomly assigned to three groups.
      Group I received etomidate and subsequently rocuronium (2 x 95% effective dose).
      Instead of etomidate, Group II received thiopental. In Group III, ephedrine 100
      mug/kg was given before thiopental; additionally, muscle blood flow was measured
      (fluorescent microspheres). Although there were differences in hemodynamics
      between Groups I and II, this was not reflected in different onset times of
      rocuronium. In Group III, ephedrine compensated the thiopental-induced decrease
      of mean arterial blood pressure, cardiac index, and muscle blood flow, but no
      significant shortening of onset time (Group I: 74 +/- 21 s; Group II: 71 +/- 24;
      Group III: 69 +/- 22 s) was found. Our results demonstrated that ephedrine
      related increases in cardiac index and blood flow did not shorten onset time of
      rocuronium in healthy pigs.

PMID- 15562059
TI  - Apoptosis is not enhanced in primary mixed neuronal/glial cultures protected by
      isoflurane against N-methyl-D-aspartate excitotoxicity.
AB  - Volatile anesthetics reduce acute excitotoxic cell death in primary
      neuronal/glial cultures. We hypothesized that cells protected by isoflurane
      against N-methyl-d-aspartate (NMDA)-induced necrosis would instead become
      apoptotic. Primary mixed neuronal/glial cultures prepared from fetal rat brain
      were exposed to dissolved isoflurane (0 mM, 0.4 mM [1.8 minimum alveolar
      anesthetic concentration], or 1.6 mM [7 minimum alveolar anesthetic
      concentration]) and NMDA (0 or 100 microM) at 37 degrees C for 30 min.
      Dizocilpine (10 microM) plus 100 microM NMDA served as a positive control.
      Necrosis and apoptosis were assessed at 24 and/or 48 h after exposure by using
      Hoechst/propidium iodide staining, terminal-deoxynucleotidyl transferase end-nick
      labeling, DNA fragmentation enzyme-linked immunoabsorbence, and caspase-3
      activity assays. NMDA increased the number of necrotic cells. Isoflurane (1.6 mM)
      and dizocilpine partially reduced cellular necrosis but did not increase the
      number of morphologically apoptotic or apoptotic-like cells resulting from
      exposure to 100 microM NMDA at 24 h. At 48 h, no evidence was found to indicate
      that cells protected by isoflurane had become apoptotic or apoptotic-like.
      However, cells protected by dizocilpine against necrosis showed evidence of
      caspase-3-mediated apoptosis. These in vitro data do not support the hypothesis
      that isoflurane protection against acute excitotoxic necrosis results in
      apoptosis.

PMID- 15562060
TI  - Potent activation of the human tandem pore domain K channel TRESK with clinical
      concentrations of volatile anesthetics.
AB  - The tandem pore domain K channel family mediates background K currents present in
      excitable cells. Currents passed by certain members of the family are enhanced by
      volatile anesthetics, thus suggesting a novel mechanism of anesthesia. The newest
      member of the family, termed TRESK (TWIK [tandem pore domain weak inward
      rectifying channel]-related spinal cord K channel), has not been studied for
      anesthetic sensitivity. We isolated the coding sequence for TRESK from human
      spinal cord RNA and functionally expressed it in Xenopus oocytes and transfected
      COS-7 cells. With both whole-cell voltage-clamp and patch-clamp recording, TRESK
      currents increased up to three-fold by clinical concentrations of isoflurane,
      halothane, sevoflurane, and desflurane. Nonanesthetics (nonimmobilizers) had no
      effect on TRESK. Various IV anesthetics, including etomidate, thiopental, and
      propofol, have a minimal effect on TRESK currents. Amide and ester local
      anesthetics inhibit TRESK in a concentration-dependent manner but at
      concentrations generally larger than those that inhibit other tandem pore domain
      K channels. We also determined that TRESK is found not only in spinal cord, but
      also in human brain RNA. These results identify TRESK as a target of volatile
      anesthetics and suggest a role for this background K channel in mediating the
      effects of inhaled anesthetics in the central nervous system.

PMID- 15562061
TI  - Sevoflurane decreases bispectral index values more than does halothane at equal
      MAC multiples.
AB  - At the minimum alveolar concentration (MAC) of inhaled anesthetics, 50% of
      subjects move in response to noxious stimulation. Similarly, at MAC-awake, 50% of
      subjects respond appropriately to command. The bispectral index (BIS) nominally
      measures the effect of anesthetics on wakefulness or consciousness. We postulated
      that the use of halothane with a larger MAC-awake/MAC ratio than sevoflurane
      would produce higher BIS values at comparable levels of MAC. We studied 33
      unpremedicated patients anesthetized by inhalation, 18 with sevoflurane and 15
      with halothane. We measured BIS before and during anesthesia at 1 MAC, both
      before and after tracheal intubation facilitated by fentanyl and rocuronium and
      then at 1.5 MAC. BIS measurements were made after meeting steady-state
      conditions. No surgery was performed during this study. BIS values in awake
      patients did not differ between the sevoflurane and halothane groups (96 +/- 2
      and 96 +/- 2, mean +/- sd, respectively). At 1 MAC without and with neuromuscular
      blockade and at 1.5 MAC, BIS values for patients anesthetized with halothane (54
      +/- 7, 56 +/- 7, and 49 +/- 7, respectively) exceeded those for patients
      anesthetized with sevoflurane (34 +/- 6, 34 +/- 6, and 29 +/- 5, respectively) (P
      < 0.0001). This finding adds to other evidence indicating that BIS is drug
      specific.

PMID- 15562062
TI  - Measuring depth of sedation with auditory evoked potentials during controlled
      infusion of propofol and remifentanil in healthy volunteers.
AB  - Avoiding excessively deep levels of sedation is a major problem in intensive care
      patients. We studied whether clinically relevant levels of sedation can be
      objectively assessed using long latency auditory evoked potentials. We measured
      the auditory evoked potentials at 100 ms after the stimulus (N100) in 10 healthy
      volunteers during stepwise increasing, clinically relevant levels of sedation
      (Ramsay score [RS] 2-4). The volunteers were studied on three separate occasions
      and received an infusion of either propofol or a combination of propofol and
      remifentanil. Effects of remifentanil infusion alone were tested during target
      controlled infusion (target plasma concentrations: 1, 2, and 3 ng/mL).
      Remifentanil did not affect evoked potential amplitudes and latencies. During
      both propofol-induced and propofol/remifentanil-induced sedation, the N100
      amplitude decreased similarly without an effect on the latencies as the level of
      sedation increased from Ramsay score 2 to Ramsay score 4 (P < 0.01). At the same
      clinical level of sedation, propofol plasma concentrations were larger when
      sedation was achieved by propofol alone (propofol versus propofol/remifentanil,
      RS 3: 2.12 mug/mL +/- 0.51 versus 1.32 +/- 0.43, P < 0.01; RS 4: 3.37 +/- 0.47
      versus 1.86 +/- 0.34, P < 0.01). Our results suggest that long latency auditory
      evoked potentials provide an objective electrophysiological analog to the
      clinical assessment of sedation independent of the sedation regime used.

PMID- 15562063
TI  - The use of high-fidelity human patient simulation and the introduction of new
      anesthesia delivery systems.
AB  - New anesthesia delivery systems are becoming increasingly complex. Although
      equipment is involved in a large proportion of intraoperative anesthesia problems
      (most also involving human error), the current methods of introducing new
      equipment into clinical practice have not been well studied. We designed a
      randomized, controlled, prospective study to investigate an alternative method of
      introducing new anesthesia equipment. Fifteen anesthesiology trainees were
      randomized to either the standard introduction to a Drager Fabius GS anesthesia
      delivery machine plus simulated clinical use of the new machine in a high
      fidelity human patient simulator (HPS) (Group 1) or to the standard introduction
      alone (Group 2). We used a questionnaire to seek their opinion on the new
      equipment, and responses showed that both groups were comparable in their
      reported confidence to use the new equipment safely. All trainees were then
      tested in two simulated anesthetic crises with the new machine. Performance was
      analyzed in terms of time to resolve the emergency, by using analysis of videos
      by an independent rater. Group 1 resolved both crises significantly faster. HPS
      allowed us to detect design features that were common sources of error.

PMID- 15562064
TI  - Conductive heat exchange with a gel-coated circulating water mattress.
AB  - The use of forced-air warming is associated with costs for the disposable
      blankets. As an alternative method, we studied heat transfer with a reusable gel
      coated circulating water mattress placed under the back in eight healthy
      volunteers. Heat flux was measured with six calibrated heat flux transducers.
      Additionally, mattress temperature, skin temperature, and core temperature were
      measured. Water temperature was set to 25 degrees C, 30 degrees C, 35 degrees C,
      and 41 degrees C. Heat transfer was calculated by multiplying heat flux by
      contact area. Mattress temperature, skin temperature, and heat flux were used to
      determine the heat exchange coefficient for conduction. Heat flux and water
      temperature were related by the following equation: heat flux = 10.3 x water
      temperature - 374 (r(2) = 0.98). The heat exchange coefficient for conduction was
      121 W . m(-2) . degrees C(-1). The maximal heat transfer with the gel-coated
      circulating water mattress was 18.4 +/- 3.3 W. Because of the small effect on the
      heat balance of the body, a gel-coated circulating water mattress placed only on
      the back cannot replace a forced-air warming system.

PMID- 15562065
TI  - A comparison of postoperative pain control in patients after right lobe donor
      hepatectomy and major hepatic resection for tumor.
AB  - After initiating a living donor liver transplant program at our institution, we
      observed that donor patients experienced significant postoperative pain despite
      the use of thoracic patient-controlled epidural analgesia (PCEA) infusion
      catheters. We retrospectively compared patients who underwent right lobe donor
      hepatectomy (RLDH, n = 15) with patients who had undergone major hepatic
      resection for tumor (MHRT, n = 15) to elucidate the cause for this observation.
      All patients had preoperative thoracic epidural catheters placed, and both groups
      had similar surgical exposure. Demographic information, intraoperative variables,
      intensity of postoperative pain by visual analog pain score (VAPS), side effects,
      total number of requested and delivered PCEA doses, and the total amount of
      bupivacaine (mg) and volume (mL) of PCEA solution administered through 48 h
      postoperatively were collected and analyzed. The RLDH group had a significantly
      longer surgical duration than did the MHRT group. The RLDH group patients had
      higher postoperative pain scores (P = 0.034), and were 2.76 (1.12-6.82, 95% CI)
      times more likely to have pain than those patients in the MHRT group. There was
      no significant difference between patient groups for the amount of bupivacaine
      and volume of PCEA solution administered. These observations may be explained, in
      part, by the longer duration of surgery in the RLDH group. The possible role of
      preemptive analgesia via PCEA infusion and better perioperative teaching of PCEA
      use are discussed; these may lead to improved early postoperative pain control in
      RLDH patients.

PMID- 15562066
TI  - The intravenous ketamine test: a predictive response tool for oral
      dextromethorphan treatment in neuropathic pain.
AB  - IV infusion tests performed to predict subsequent response to oral analgesics are
      an increasingly popular method used to enhance medical care and conserve
      resources. Because no infusion test is completely accurate, the potential
      benefits of these tests must be weighed against the frustration and waste in
      resources encountered with false-positive results, and the failure to use a
      potentially beneficial treatment with false-negative results. In recent years,
      drugs that act antagonistically at N-methyl-d-aspartate receptors have been shown
      to be valuable adjuncts in the treatment of pain. To determine the predictive
      value of small-dose (0.1 mg/kg) IV ketamine on an oral dextromethorphan (DX)
      treatment regimen, we analyzed the analgesic response to these drugs in 25
      patients at 2 tertiary care military treatment facilities, institutions at which
      DX is not readily accessible. When >/=50% response for both drugs was used as the
      outcome measure for success, the positive predictive value of the ketamine test
      was 64%, the negative predictive value 73%, and the observed agreement 68%.
      However, when >/=67% relief with ketamine was used as an outcome measure (as
      determined by a receiver operating characteristic curve), the positive predictive
      value was 90%, the negative predictive value 80%, and the observed agreement
      increased to 84%. Based on these results, we conclude that an IV ketamine test
      may be useful in predicting response to oral DX. More research is needed to
      determine the ideal candidates for such a test, and the optimal dose and cutoff
      value for the response to ketamine.

PMID- 15562067
TI  - Epidural blood patch and acute varicella.
AB  - We present the case of a 38-yr-old woman who required an epidural blood patch in
      the context of acute varicella (chickenpox). The unique risks in this case
      include the possible triggering of central nervous system complications after the
      introduction of viremic blood into the epidural or intrathecal space. However,
      the risk was believed to be acceptable because the patient was receiving
      antiviral coverage. She enjoyed complete relief of her headache but experienced
      transient back and leg pain. Leptomeningeal irritation caused by acute varicella
      infection may put patients at increased risk for pain after epidural blood patch.

PMID- 15562068
TI  - Intrinsic spinal cord catheter placement: implications of new intractable pain in
      a patient with a spinal cord injury.
AB  - We present a case of new intractable flank pain after intrathecal infusion system
      placement in a 45-yr-old man with a history of a T12 spinal cord injury with
      dysesthetic leg pain. Pain after intrathecal infusion system placement was
      evaluated by magnetic resonance imaging and the catheter was found to be
      intraparenchymal. The patient was treated by cessation of infusion and surgical
      removal of the system. Before surgical removal, the pump was turned off and the
      patient's flank pain resolved. Increased vigilance is warranted when caring for
      paraplegic patients. When new pain persists, intrathecal medication tapering
      should be considered.

PMID- 15562069
TI  - Anesthesiologists, general surgeons, and tobacco interventions in the
      perioperative period.
AB  - Surgery presents an opportunity for interventions in cigarette smokers that will
      facilitate abstinence from tobacco. However, little attention has been paid to
      the role of anesthesiologists and surgeons in addressing tobacco use. To
      determine the practices and attitudes of these physicians regarding this issue,
      we sent a postal mail survey to a national random sampling of anesthesiologists
      and general surgeons engaged in active practice within the United States (1000 in
      each group). Response rates were 33% and 31% for anesthesiologists and surgeons,
      respectively. More than 90% of both groups almost always ask their patients about
      tobacco use, and almost all respondents believed that surgical patients should
      maintain abstinence after surgery. Most believed that it was their responsibility
      to advise their patients to quit smoking, but only 30% of anesthesiologists and
      58% of surgeons routinely do so. Nonetheless, approximately 70% of both groups
      would be willing to spend an extra 5 min before surgery to help their patients
      quit. Barriers to intervention included a lack of training regarding intervention
      techniques, a perceived lack of effective interventions, and insufficient time to
      intervene. Intervention opportunities are not exploited consistently in the
      surgical population; educational efforts directed at physicians in surgical
      specialties are indicated.

PMID- 15562070
TI  - Risk factors assessment of the difficult airway: an italian survey of 1956
      patients.
AB  - Over the last decade, there has been a heightened awareness and an increase in
      the amount of literature being published on recognition and prediction of the
      difficult airway. During the preoperative evaluation of the airway, a thorough
      history and physical specifically related to the airway should be performed.
      Various measurements of anatomic features and noninvasive clinical tests can be
      performed to enhance this assessment. In this study we correlated the Mallampati
      modified score and several other indexes with the laryngoscopic view to identify
      anatomical and clinical risk factors related to the difficult airway. We
      prospectively collected data on 1956 consecutive patients scheduled to receive
      general anesthesia requiring endotracheal intubation for elective surgery. The
      Mallampati classification versus the Cormack-Lehane (C-L) linear correlation
      index was 0.904. A Mallampati Class 3 correlated with a C-L Grade 2 (0.94),
      whereas a Mallampati Class 4 correlated with a C-L Grade 3 (0.85) and a C-L Grade
      4 (0.80). Operator evaluation, performed by a simplified tracheal intubation
      difficulty scale, showed a linear correlation of 0.96 compared with the C-L
      groups. Although there is a correlation between oropharyngeal volume and
      difficult intubation, the Mallampati score by itself is insufficient for
      predicting difficult endotracheal intubation.

PMID- 15562071
TI  - A comparison of changes in cardiac preload variables during graded hypovolemia
      and hypervolemia in mechanically ventilated dogs.
AB  - We developed an online monitoring system to measure systolic blood pressure
      variation (SPV) and its down (dDown) and up components, along with pulse pressure
      variation (dPP). Using the system, we compared different cardiac preload
      indicators-such as stroke volume variation (SVV) and corrected flow time (FTc)
      along with central venous pressure and pulmonary artery occlusion pressure in
      mechanically-ventilated dogs during normovolemia, graded hypovolemia (-200 and 
      350 mL), and hypervolemia (+200 and +350 mL). We simultaneously measured these
      preload indicators along with global hemodynamic variables and investigated their
      validity and limitations to access preload changes. SPV increased from 4.8 +/-
      1.4 mm Hg at baseline to 11.2 +/- 1.8 mm Hg during hypovolemia (-350 mL), but it
      did not change significantly during hypervolemia. Similar changes were observed
      with dDown, dPP, and SVV. FTc, conversely, increased during hypervolemia but
      remained unchanged during hypovolemia. The results of this study indicate that
      SPV, dDown, dPP, and SVV are useful indicators of hypovolemia, but not of
      hypervolemia. Conversely, hypovolemia could not be detected reliably by FTc, but
      it does reflect blood volume changes during hypervolemia. Although SPV, dDown,
      and dPP measurements require no additional invasion and cost beyond arterial
      cannulation, their limits must be kept in mind for the monitoring of blood volume
      status in mechanically-ventilated patients.

PMID- 15562072
TI  - Ventricular fibrillation median frequency may not be useful for monitoring during
      cardiac arrest treated with endothelin-1 or epinephrine.
AB  - In this study, we evaluated whether median fibrillation frequency (MF) and mean
      fibrillation amplitude (AMP) reflect coronary perfusion pressure (CoPP) and
      predict successful defibrillation. MF, AMP, and CoPP were measured during
      prolonged ventricular fibrillation (VF) cardiac arrest and resuscitation in pigs.
      After 5 min of VF, cardiopulmonary resuscitation was started. At 10 min, the pigs
      received randomly a single dose of endothelin-1 50 mug (n = 7), 100 mug (n = 7),
      or 200 mug (n = 5), or repeated doses of epinephrine 0.04 mg/kg (n = 6), or
      saline (n = 6) every 3 min. At 25 min, the pigs were defibrillated to achieve
      restoration of spontaneous circulation (ROSC). In a nonparametric spectral
      analysis of the individual MF versus CoPP and AMP versus CoPP curves, we found no
      link between the different curves in different animals or therapies. No
      difference was found in MF in pigs with ROSC (n = 8) compared with animals not
      achieving ROSC (n = 23) immediately before defibrillation (P = 0.85). Our data
      suggest that, in prolonged VF cardiac arrest, MF and AMP might not be useful
      tools to reflect myocardial perfusion.

PMID- 15562073
TI  - A novel method to assess platelet inhibition by eptifibatide with
      thrombelastograph.
AB  - We examined a novel method to detect platelet inhibition with thrombelastography
      (TEG). We hypothesized that this method would be suitable for monitoring the
      antiplatelet effects of eptifibatide (Integrilin). Whole blood from healthy
      volunteers was anticoagulated with 3.2% citrate or unfractionated heparin (7
      IU/mL). For the platelet aggregation test, both citrate and heparinized samples
      were spiked with increasing concentrations of eptifibatide (0, 0.2, 0.4, 0.8,
      1.6, and 4 microg/mL). Conventional kaolin TEG was performed with citrated
      samples, and batroxobin-modified TEG was performed with heparinized samples,
      which were spiked with eptifibatide at concentrations of 0, 0.4, 0.8, 1.6, 4, 8,
      and 24 microg/mL. Adenosine 5'-diphosphate-induced platelet aggregation was
      reduced to 6.4% +/- 2.9% (citrate) and 10.3% +/- 4.8% (heparin) with eptifibatide
      at the concentration of 4 mug/mL. The kaolin TEG showed a decrease in maximum
      amplitude (MA) only at the eptifibatide concentration of 24 mug/mL and no change
      in alpha angle, whereas with the batroxobin-based TEG, the difference in MA and
      alpha angle was observed at concentrations >/=0.8 microg/mL. Additionally, the
      time to achieve maximum MA was much shorter for batroxobin TEG than for kaolin
      TEG. We conclude that the batroxobin-modified TEG is a sensitive method that
      detects platelet inhibition induced by eptifibatide.

PMID- 15562074
TI  - Increased carboxyhemoglobin in a patient with a large retroperitoneal hematoma.
AB  - In humans, the sole endogenous source of carbon monoxide is heme degradation. We
      report the development of prolonged carboxyhemoglobinemia in a critically ill
      mechanically ventilated patient who required massive transfusion because of
      retroperitoneal hemorrhage secondary to pheochromocytoma. After the transfusion
      of 27 U of packed red blood cells, the maximum carboxyhemoglobin level was 6.4%.
      Although ventilation was controlled with a fraction of inspired oxygen of 0.35
      0.5 and external drainage of blood occurred, the concentration of
      carboxyhemoglobin remained at 1.7%-5.6% for days. Red blood cells for transfusion
      may be contaminated with carbon monoxide and may have carboxyhemoglobin levels of
      up to 12%; this may also have contributed to carboxyhemoglobinemia in our
      patient. If significantly increased concentrations of carboxyhemoglobin develop,
      therapy to decrease the concentration of carboxyhemoglobin (such as fraction of
      inspired oxygen of 1.0 and/or minute ventilation or hyperbaric oxygen) or removal
      of the source should be considered.

PMID- 15562075
TI  - Hepatic hydrothorax in the absence of ascites: respiratory failure in a cirrhotic
      patient.
AB  - The frequency of hepatic hydrothorax in cirrhotic patients is reported to be
      approximately 5%. The pleural effusion is predominantly right-sided (85% of
      cases) but may be bilateral. Although most often accompanied by significant
      ascites, it can occur in its absence. We report a case of a right-sided acute
      hepatic hydrothorax as a result of residual motor blockade during anesthesia
      recovery and without previous evidence of clinical ascites. This complication
      should be considered by the anesthesiologist in every cirrhotic patient, with or
      without clinical evidence of ascites.

PMID- 15562076
TI  - Is intrathecal magnesium sulfate safe and protective against ischemic spinal cord
      injury in rabbits?
AB  - We performed three sets of experiments to investigate the safety of intrathecal
      magnesium and to determine its optimal dose for protection, if any, against
      ischemic spinal cord injury in rabbits. First, we examined neurotoxicity of 0.3,
      1, 2, or 3 mg/kg of magnesium sulfate (n = 6 each). Significant sensory
      dysfunction was observed in the 3-mg/kg group 7 days after administration. Motor
      dysfunction was found in two rabbits in both the 2- and 3-mg/kg groups. The area
      of destruction in laminae V-VII was observed in one, two, and one rabbit in the 1
      , 2-, and 3-mg/kg groups, respectively. Second, we investigated the temporal
      profile (6 h, 48 h, and 96 h [n = 3 each]) of histopathologic changes after 3
      mg/kg of magnesium sulfate and confirmed similar changes in the rabbits with
      motor dysfunction at 48 and 96 h. Third, we evaluated the effects of 0.3 mg/kg or
      1 mg/kg of magnesium sulfate or saline (n = 6 each) administered before ischemia
      on hindlimb motor function and histopathology after spinal cord ischemia (15
      min). Magnesium did not improve neurologic or histopathologic outcome 96 h after
      reperfusion. The results indicate that intrathecal magnesium has a risk of
      neurotoxicity and shows no evidence of protective effects against ischemic spinal
      cord injury.

PMID- 15562077
TI  - Acute adrenal insufficiency after large-dose glucocorticoids for spinal cord
      injury.
AB  - A 24- to 48-h course of large-dose glucocorticoid therapy is often used in the
      acute management of spinal cord injury. We describe a patient who developed
      adrenal insufficiency (AI) after this protocol. Although a definitive causal
      relationship between the steroids and AI was not established, their temporal
      association and the exclusion of other possible etiologies led us to postulate
      that AI was a complication of the steroid protocol. Clinicians should, therefore,
      consider AI in patients with spinal cord injury receiving glucocorticoids, a
      population in whom it may otherwise go undiagnosed and untreated.

PMID- 15562078
TI  - Iatrogenic arteriovenous fistula during lumbar microdiscectomy.
AB  - Vascular lacerations, arteriovenous fistulae, and pseudoaneurysms are rare, but
      potentially life threatening, complications of lumbar disk surgery. These
      iatrogenic vascular injuries may present with significant hypotension during the
      perioperative period. Early diagnosis and surgical repair may decrease morbidity
      and mortality. We discuss perioperative implications of postdiscectomy vascular
      injuries in this report.

PMID- 15562079
TI  - Using heart rate variability to stratify risk of obstetric patients undergoing
      spinal anesthesia.
AB  - In this study, we evaluated whether point correlation dimension (PD2), a measure
      of heart rate variability, can predict hypotension accompanying spinal anesthesia
      for cesarean delivery. After the administration of spinal anesthesia with
      bupivacaine, hypotension was defined as systolic blood pressure </=75% of
      baseline within 20 min of intrathecal injection. Using the median prespinal PD2
      (3.90) to form 2 groups, LO and HI, all 11 hypotensive patients were in the LO
      group, and all 11 patients without hypotension were in the HI group. Baseline
      heart rate in the LO group was 95 bpm (10.2 sd), versus 81 bpm (9.6 sd) in the HI
      group. PD2 shows promise as a predictor of hypotension in pregnant women
      receiving spinal anesthesia.

PMID- 15562080
TI  - Determining minimum alveolar anesthetic concentration of halothane in rats: the
      effect of incremental change in halothane concentration and number of crossovers.
AB  - Computer simulations for the technique of estimating minimum alveolar anesthetic
      concentration (MAC) in patients (quantal design) suggest that incremental
      concentration changes and the number of crossovers affect MAC. We hypothesized
      that these variables may also apply to estimating MAC in rats (bracketing
      design). This study tested that hypothesis and also examined whether these
      variables might mask differences in MAC between groups in which MAC might be
      expected to differ (pregnant [P] versus nonpregnant [NP]). There were 2 cohorts
      (n = 27 and n = 30 rats). Each cohort included NP females, females in early P,
      and females in late P. MAC was tested by using an incremental concentration
      change of 0.20% and one within-subject crossover in the first cohort and by using
      an increment size of 0.10% and four crossovers in the second cohort. MAC was
      statistically significantly increased in the three groups in the second cohort
      (NP, 1.16 +/- 0.12; early P, 1.14 +/- 0.10; late P, 1.07 +/- 0.10; mean +/- sd)
      compared with values in the three comparable groups in the first cohort (NP, 0.95
      +/- 0.06; early P, 1.01 +/- 0.09; late P, 0.93 +/- 0.13). Values did not differ
      among groups within each cohort. Post hoc simulations indicated that up to 36% of
      the difference between cohorts was due to increment size, with the balance due to
      experimental factors. Our findings confirmed the hypothesis that increment size
      affects estimates of MAC when a bracketing design is used.

PMID- 15562081
TI  - Paramedian lumbar epidural catheter insertion with patients in the sitting
      position is equally successful in the flexed and unflexed spine.
AB  - Positioning for placement of an epidural catheter can be quite painful for
      patients with lower limb injuries. We randomly allocated 50 patients scheduled
      for surgery after lower limb injuries for placement of a lumbar epidural catheter
      in the sitting position with the back in the neutral unflexed position by either
      the midline or paramedian approach. If the approach failed after two attempts,
      patients were placed in a flexed-spine position, and the procedure was attempted
      again. Technical difficulties and complications were recorded. In 17 patients in
      the midline group, and 1 patient in the paramedian group, it was not possible to
      insert the needle initially, and a flexed-spine position was required (P < 0.05).
      The incidences of resistance to catheter insertion (eight versus one),
      paresthesia (seven versus zero), and appearance of blood in the catheter (six
      versus zero) were significantly more frequent in the midline compared with the
      paramedian approach. The midline group also experienced more discomfort than the
      paramedian group. We conclude that, with the patient sitting with an unflexed
      spine, it is usually possible to insert an epidural catheter with the paramedian
      approach.

PMID- 15562082
TI  - Cervical epidural anesthesia for combined neck and upper extremity procedure: a
      pilot study.
AB  - In a prospective pilot study, we evaluated the possibility of performing a total
      parathyroidectomy with parathyroid gland implantation into the forearm (a
      combined neck and upper extremity procedure) under cervical epidural anesthesia
      (CEA) at C6-7 level using ropivacaine. The indication for CEA was the patient's
      choice or a previous procedure on the neck with unilateral vocal cord paralysis.
      Anesthesia was induced by 10 mL of 0.75% ropivacaine plus 10 mug of sufentanil in
      2 mL. Block onset time, success rate, analgesia, sensory block extent, changes in
      respiratory and hemodynamic variables, complications, and length of hospital stay
      were assessed. All 15 procedures were successfully performed under CEA. Sensory
      block was registered in the range C2-T10, with a lower median of T3. The upper
      margin of sensory block was C2 in all patients. Of the respiratory variables, the
      only significant decrease was observed in forced vital capacity; none of the
      patients developed clinically significant respiratory insufficiency. We conclude
      that combined procedures involving the neck and upper limbs can be performed
      using CEA with ropivacaine. CEA allows verbal communication with patients and
      early detection of vocal cord paralysis.

PMID- 15562083
TI  - Single-injection paravertebral block before general anesthesia enhances analgesia
      after breast cancer surgery with and without associated lymph node biopsy.
AB  - Paravertebral block (PVB) seems to decrease postoperative pain and postoperative
      nausea and vomiting (PONV) after breast surgery, but the studies have not been
      placebo controlled. We studied 60 patients scheduled for breast cancer surgery
      randomly given single-injection PVB at T3 with bupivacaine 5 mg/mL (1.5 mg/kg) or
      saline before general anesthesia. The patient and attending investigators were
      blinded; the PVB or the sham block was performed behind a curtain by an
      anesthesiologist not involved in the study. The patients given PVB with
      bupivacaine needed 40% less IV opioid medication (primary outcome variable) in
      the postanesthesia care unit, had a longer latency to the first opioid dose, and
      had less pain at rest after 24 h than the control patients (P < 0.01). They also
      had less PONV in the postanesthesia care unit (P < 0.05), were less sedated until
      90 min (P < 0.05), and performed better in the digit symbol substitution test at
      90 min and the ocular coordination test 60-120 min after surgery (P < 0.05). The
      average peak bupivacaine plasma concentration was 750 ng/mL. One patient had
      bilateral convulsions immediately after bupivacaine injection. We conclude that
      PVB before general anesthesia for breast cancer surgery reduced postoperative
      pain, opioid consumption, and occurrence of PONV and improved recovery from
      anesthesia.

PMID- 15562084
TI  - The mechanical properties of continuous spinal small-bore catheters.
AB  - Continuous spinal anesthesia (CSA) has a nearly 100-yr history. In situations of
      difficult removal of a CSA small-bore catheter, mechanical properties of the
      different catheters might be important, because breakage could occur. We compared
      5 different CSA small-bore catheters, 22- to 28-gauge from 3 manufacturers, for
      tensile strength, tensile stress, distension, and yield strength. Maximal tensile
      strength is the force applied before breakage of the catheter. The material
      characteristics of different CSA small-bore catheters for maximal tensile
      strength were: 22-gauge = 29.56 +/- 1.56 (mean +/- sd) Newton (N), 24-gauge =
      16.77 +/- 1.61 N, 25-gauge = 9.20 +/- 0.48 N, 27-gauge = 4.61 +/- 0.25 N, 28
      gauge = 5.07 +/- 0.59 N at room temperature. A strong correlation between maximal
      tensile strength and the outer diameter (r = 0.957, P < 0.001) and maximal
      tensile strength and the wall thickness (r = 0.9, P < 0.001) was observed.
      Although extrapolation from experimental studies to clinical routine should be
      made with care, our data suggest that catheters with higher-strength
      characteristics may reduce the risk of catheter breakage in patients, although
      clinical correlations are lacking.

PMID- 15562085
TI  - Emergence and recovery characteristics of desflurane versus sevoflurane in
      morbidly obese adult surgical patients: a prospective, randomized study.
AB  - We compared postoperative recovery after desflurane (n = 25) versus sevoflurane
      (n = 25) anesthesia in morbidly obese adults (body mass index >/=35) who
      underwent gastrointestinal bypass surgery via an open laparotomy. After
      premedication with midazolam and metoclopramide 1 h before surgery, epidural
      catheter placement, induction of anesthesia with fentanyl and propofol, and
      tracheal intubation facilitated with succinylcholine, anesthesia was maintained
      with age-adjusted 1 minimum alveolar concentration (MAC) desflurane or
      sevoflurane. Fentanyl IV, morphine or local anesthetics epidurally, and
      vasoactive drugs as needed were used to maintain arterial blood pressure at +/
      20% of baseline value and to keep bispectral index of the electroencephalogram
      values between 40 to 60 U. Although patients were anesthetized with desflurane
      for a longer time (261 +/- 50 min versus 234 +/- 37 min, mean +/- sd; P < 0.05,
      desflurane versus sevoflurane, respectively) and for more MAC-hours (4.2 +/- 0.9
      h versus 3.7 +/- 0.8 h; P < 0.05), significantly earlier recovery of response to
      command and tracheal extubation occurred in patients given desflurane than in
      patients given sevoflurane. The modified Aldrete score was greater in desflurane
      anesthetized patients on admission to the postanesthesia care unit (PACU) (P =
      0.01) but not at discharge (P = 0.47). On admission to PACU, patients given
      desflurane had higher oxygen saturations (97.0% +/- 2.4%) than patients given
      sevoflurane (94.8% +/- 4.4%, P = 0.035). Overall, the incidence of postoperative
      nausea and vomiting and the use of antiemetics did not differ between the two
      anesthetic groups. We conclude that morbidly obese adult patients who underwent
      major abdominal surgery in a prospective, randomized study awoke significantly
      faster after desflurane than after sevoflurane anesthesia and the patients
      anesthetized with desflurane had higher oxygen saturation on entry to the PACU.

PMID- 15562086
TI  - The volume kinetics of acetated Ringer's solution during laparoscopic
      cholecystectomy.
AB  - We studied the distribution and elimination of an IV infusion of 20 mL/kg of
      acetated Ringer's solution (approximately 1500 mL) over 60 min in 12 women
      undergoing laparoscopic cholecystectomy. A plasma dilution of 4.2% developed
      during the induction of general anesthesia, even though fluid was withheld. The
      additional plasma dilution induced by the subsequent volume expansion was
      slightly larger than expected from previous volunteer experiments and averaged
      18%. The diuretic response to intravascular fluid administration was small, and
      only 20% of the infused fluid had been excreted 4 h later. Volume kinetic
      analysis showed that the IV fluid expanded a central body fluid space by 3.2 L.
      The clearance constants for distribution and elimination averaged 115 mL/min and
      6.8 mL/min, respectively. These data represent a half-life of the fluid in the
      patients that is 17 times longer (median, 4.5 h) than the half-life of the plasma
      dilution (16 min), indicating a strong tendency to the formation of peripheral
      edema. A nomogram based on the kinetic variables suggests that infusion rates
      should be relatively rapid early on during surgery but slower later. This
      strategy creates a constant plasma dilution at any desired level without causing
      undue peripheral accumulation of fluid.

PMID- 15562087
TI  - Venous oxygen embolism produced by injection of hydrogen peroxide into an
      enterocutaneous fistula.
AB  - We report a venous oxygen embolism that occurred in a 66-yr-old man after 60 mL
      of 3% hydrogen peroxide was injected into a perianal fistula intraoperatively to
      locate its internal opening. The diagnosis was made after detecting hypoxemia,
      decreased end-tidal carbon dioxide tension, systemic hypotension, increased
      central venous pressure, and a new heart murmur. The patient recovered quickly
      and had no long-term sequelae. Oxygen embolism is a potentially fatal
      complication that can develop when hydrogen peroxide is used near venous spaces,
      and clinicians should be aware of the potential dangers when using this seemingly
      innocuous chemical.

PMID- 15562088
TI  - Venous air embolism during transurethral resection of the prostate.
AB  - Venous air embolism during transurethral surgery is a rare event. There have been
      case reports in the anesthesia and urology literature of fatal air embolism
      during transurethral prostate resection and transurethral incision of the bladder
      neck. We present a case of nonfatal venous air embolism during transurethral
      prostate resection in which incorrect assembly of the bladder irrigation
      resectoscope-drain system led to a rapid entrainment of air into the open venous
      channels of the prostate bed.

PMID- 15562089
TI  - Hypertensive crisis in a patient undergoing percutaneous radiofrequency ablation
      of an adrenal mass under general anesthesia.
AB  - Radiofrequency ablation (RFA) is an effective therapeutic intervention for a
      variety of neoplastic lesions. Many of these procedures are conducted with
      patients under general anesthesia. Although RFA is associated with infrequent
      complications, it is not without risk. Injury to adjacent normal structures is a
      major concern during RFA of cancerous lesions. Unintended injury to normal
      adrenal tissue during RFA of adrenal tumors can lead to hypertensive crisis, a
      potentially catastrophic complication. Hemodynamic consequences of RFA of primary
      or metastatic adrenal masses have not been reported. We report a case of
      hypertensive crisis (249/140 mm Hg), tachycardia, and ventricular arrhythmia in
      an 82-yr-old woman undergoing RFA of renal cell carcinoma metastatic to the
      adrenal gland. Anesthesiologists should be aware of this potentially catastrophic
      complication. Direct-acting vasodilators and short-acting beta(1)-adrenergic
      antagonists should be immediately available, and intraarterial blood pressure
      monitoring should be seriously considered when providing care for patients
      undergoing RFA of an adrenal mass.

PMID- 15562091
TI  - The use of pulse oximeter functional testers in evaluating Spo2 accuracy.

PMID- 15562092
TI  - Can organophosphates facilitate acute tongue necrosis?

PMID- 15562093
TI  - Bleeding diathesis due to failed antagonism of heparin: successful treatment with
      recombinant factor VIIa.

PMID- 15562094
TI  - Hypertensive encephalopathy mimicking postdural puncture headache in a parturient
      beyond the edge of reproductive age.

PMID- 15562095
TI  - Difficult airway in obstetric using Ilma-Fastrach.

PMID- 15562096
TI  - Pin-pricks and pins' tricks: a new method to reduce pin-prick pain of
      intramuscular and subcutaneous injections.

PMID- 15562097
TI  - The supraclavicular block with a nerve stimulator: where is the needle tip, that
      is the question.

PMID- 15562098
TI  - The change of difficult intubation with growth in a patient with treacher Collins
      syndrome.

PMID- 15562099
TI  - Lipid, not propofol, treats bupivacaine overdose.

PMID- 15562100
TI  - Does modafinil improve recovery?

PMID- 15562101
TI  - Omentum through the vulva as first sign of a uterine rupture.

PMID- 15562102
TI  - Intubating laryngeal mask airway in lateral position.

PMID- 15562103
TI  - Postoperative analgesia and recovery after open and laparoscopic prostatectomy.

PMID- 15562104
TI  - Hyperbaric oxygen therapy and pain management in a child with continuous
      infraclavicular brachial plexus block.

PMID- 15562105
TI  - MRI of the upper airway and McCoy-balloon laryngoscopy with left molar approach
      in a patient with arthrogryposis multiplex congenita and previous unsuccessful
      endotracheal intubation.

PMID- 15562106
TI  - Prick testing for neuromuscular blocking drugs.

PMID- 15562107
TI  - Should CO2 laser jet ventilation be abandoned?

PMID- 15562108
TI  - Growing role for umbilical cord blood.

PMID- 15562109
TI  - Medical books from the cradle delight in a digital age.

PMID- 15562117
TI  - Systolic hypertension in elderly persons.

PMID- 15562118
TI  - Systolic hypertension in elderly persons.

PMID- 15562119
TI  - Erectile dysfunction in obese men.

PMID- 15562120
TI  - Erectile dysfunction in obese men.

PMID- 15562121
TI  - Erectile dysfunction in obese men.

PMID- 15562122
TI  - WHO survey of prevalence of mental health disorders.

PMID- 15562123
TI  - Erectile dysfunction in obese men.

PMID- 15562124
TI  - Association between antibiotic sales and public campaigns for their appropriate
      use.

PMID- 15562125
TI  - Obesity and the risk of new-onset atrial fibrillation.
AB  - CONTEXT: Obesity is associated with atrial enlargement and ventricular diastolic
      dysfunction, both known predictors of atrial fibrillation (AF). However, it is
      unclear whether obesity is a risk factor for AF. OBJECTIVE: To examine the
      association between body mass index (BMI) and the risk of developing AF. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective, community-based observational cohort in
      Framingham, Mass. We studied 5282 participants (mean age, 57 [SD, 13] years; 2898
      women [55%]) without baseline AF (electrocardiographic AF or arterial flutter).
      Body mass index (calculated as weight in kilograms divided by square of height in
      meters) was evaluated as both a continuous and a categorical variable (normal
      defined as <25.0; overweight, 25.0 to <30.0; and obese, > or =30.0). In addition
      to adjusting for clinical confounders by multivariable techniques, we also
      examined models including echocardiographic left atrial diameter to examine
      whether the influence of obesity was mediated by changes in left atrial
      dimensions. MAIN OUTCOME MEASURE: Association between BMI or BMI category and
      risk of developing new-onset AF. RESULTS: During a mean follow-up of 13.7 years,
      526 participants (234 women) developed AF. Age-adjusted incidence rates for AF
      increased across the 3 BMI categories in men (9.7, 10.7, and 14.3 per 1000 person
      years) and women (5.1, 8.6, and 9.9 per 1000 person-years). In multivariable
      models adjusted for cardiovascular risk factors and interim myocardial infarction
      or heart failure, a 4% increase in AF risk per 1-unit increase in BMI was
      observed in men (95% confidence interval [CI], 1%-7%; P = .02) and in women (95%
      CI, 1%-7%; P = .009). Adjusted hazard ratios for AF associated with obesity were
      1.52 (95% CI, 1.09-2.13; P = .02) and 1.46 (95% CI, 1.03-2.07; P = .03) for men
      and women, respectively, compared with individuals with normal BMI. After
      adjustment for echocardiographic left atrial diameter in addition to clinical
      risk factors, BMI was no longer associated with AF risk (adjusted hazard ratios
      per 1-unit increase in BMI, 1.00 [95% CI, 0.97-1.04], P = .84 in men; 0.99 [95%
      CI, 0.96-1.02], P = .56 in women). CONCLUSIONS: Obesity is an important,
      potentially modifiable risk factor for AF. The excess risk of AF associated with
      obesity appears to be mediated by left atrial dilatation. These prospective data
      raise the possibility that interventions to promote normal weight may reduce the
      population burden of AF.

PMID- 15562126
TI  - Guillain-Barre syndrome following influenza vaccination.
AB  - CONTEXT: An unexplained increase in the risk of Guillain-Barre syndrome (GBS)
      occurred among recipients of the swine influenza vaccine in 1976-1977. Guillain
      Barre syndrome remains the most frequent neurological condition reported after
      influenza vaccination to the Vaccine Adverse Events Reporting System (VAERS)
      since its inception in 1990. OBJECTIVE: To evaluate trends of reports to VAERS of
      GBS following influenza vaccination in adults. DESIGN, SETTING, AND PARTICIPANTS:
      VAERS is the US national spontaneous reporting system for adverse events
      following vaccination. Reports of GBS in persons 18 years or older following
      influenza vaccination were evaluated for each influenza season from July 1, 1990,
      through June 30, 2003. The number of people vaccinated was estimated from the
      National Health Interview Survey and US census data. Beginning in 1994, active
      follow-up was conducted to verify GBS diagnosis and obtain other clinical
      details. MAIN OUTCOME MEASURE: Reporting rates of GBS following influenza
      vaccination over time. RESULTS: From July 1990 through June 2003, VAERS received
      501 reports of GBS following influenza vaccination in adults. The median onset
      interval (13 days) was longer than that of non-GBS reports of adverse events
      after influenza vaccine (1 day) (P<.001). The annual reporting rate decreased 4
      fold from a high of 0.17 per 100,000 vaccinees in 1993-1994 to 0.04 in 2002-2003
      (P<.001). A GBS diagnosis was confirmed in 82% of reports. Preceding illness
      within 4 weeks of vaccination was identified in 24% of reported cases.
      CONCLUSIONS: From 1990 to 2003, VAERS reporting rates of GBS after influenza
      vaccination decreased. The long onset interval and low prevalence of other
      preexisting illnesses are consistent with a possible causal association between
      GBS and influenza vaccine. These findings require additional research, which can
      lead to a fuller understanding of the causes of GBS and its possible relationship
      with influenza vaccine.

PMID- 15562127
TI  - Effects of a low-glycemic load diet on resting energy expenditure and heart
      disease risk factors during weight loss.
AB  - CONTEXT: Weight loss elicits physiological adaptations relating to energy intake
      and expenditure that antagonize ongoing weight loss. OBJECTIVE: To test whether
      dietary composition affects the physiological adaptations to weight loss, as
      assessed by resting energy expenditure. DESIGN, STUDY, AND PARTICIPANTS: A
      randomized parallel-design study of 39 overweight or obese young adults aged 18
      to 40 years who received an energy-restricted diet, either low-glycemic load or
      low-fat. Participants were studied in the General Clinical Research Centers of
      the Brigham and Women's Hospital and the Children's Hospital, Boston, Mass,
      before and after 10% weight loss. The study was conducted from January 4, 2001,
      to May 6, 2003. MAIN OUTCOME MEASURES: Resting energy expenditure measured in the
      fasting state by indirect calorimetry, body composition by dual-energy x-ray
      absorptiometry, cardiovascular disease risk factors, and self-reported hunger.
      RESULTS: Resting energy expenditure decreased less with the low-glycemic load
      diet than with the low-fat diet, expressed in absolute terms (mean [SE], 96 [24]
      vs 176 [27] kcal/d; P = .04) or as a proportion (5.9% [1.5%] vs 10.6% [1.7%]; P =
      .05). Participants receiving the low-glycemic load diet reported less hunger than
      those receiving the low-fat diet (P = .04). Insulin resistance (P = .01), serum
      triglycerides (P = .01), C-reactive protein (P = .03), and blood pressure (P =
      .07 for both systolic and diastolic) improved more with the low-glycemic load
      diet. Changes in body composition (fat and lean mass) in both groups were very
      similar (P = .85 and P = .45, respectively). CONCLUSIONS: Changes in dietary
      composition within prevailing norms can affect physiological adaptations that
      defend body weight. Reduction in glycemic load may aid in the prevention or
      treatment of obesity, cardiovascular disease, and diabetes mellitus.

PMID- 15562128
TI  - Effectiveness of a mass immunization campaign using serogroup C meningococcal
      conjugate vaccine.
AB  - CONTEXT: Meningococcal polysaccharide vaccines are of limited effectiveness. New
      protein-polysaccharide conjugate vaccines have yet to be evaluated in field
      conditions. OBJECTIVE: To assess the effectiveness of a serogroup C conjugate
      meningococcal vaccine in an outbreak setting. DESIGN, SETTING, AND PARTICIPANTS:
      Population-based observational study of cases of invasive serogroup C
      meningococcal disease from 1996 through 2002 in Quebec identified from the
      provincial registry of notifiable diseases and from the provincial reference
      laboratory. In 2001, a mass immunization campaign with a conjugate vaccine was
      conducted to control an emerging epidemic. The number of vaccinated individuals
      was extracted from meningococcal immunization registries. MAIN OUTCOME MEASURES:
      Incidence of invasive meningococcal disease before and 1 year after the campaign
      in vaccinated and unvaccinated individuals. RESULTS: Vaccination coverage of
      those 2 months to 20 years was 82.1%. After the campaign, the number of cases of
      serogroup C disease decreased from 58 in 2001 to 27 in 2002, and the incidence
      from 7.8 per million to 3.6 per million. Vaccine effectiveness was found to be
      96.8% (95% confidence interval, 75.0%-99.9%). There was no observed increase in
      the incidence of the other serogroups. CONCLUSION: The new conjugate vaccine was
      effective in controlling an emerging epidemic of serogroup C meningococcal
      disease, as well as providing short-term protection across a wide age range.

PMID- 15562129
TI  - Trends in cardiovascular complications of diabetes.
AB  - CONTEXT: Despite reductions in cardiovascular disease (CVD) mortality over the
      past few decades, it is unclear whether adults with and without diabetes have
      experienced similar declines in CVD risk. OBJECTIVE: To determine whether adults
      with and without diabetes experienced similar declines in incident CVD in 1950
      1995. DESIGN, SETTING, AND PARTICIPANTS: Participants aged 45-64 years from the
      Framingham Heart Study original and offspring cohorts who attended examinations
      in 1950-1966 ("earlier" time period; 4118 participants, 113 with diabetes) and
      1977-1995 ("later" time period; 4063 participants, 317 with diabetes). Incidence
      rates of CVD among those with and without diabetes were compared between the
      earlier and later periods. MAIN OUTCOME MEASURES: Myocardial infarction, coronary
      heart disease death, and stroke. RESULTS: Among participants with diabetes, the
      age- and sex-adjusted CVD incidence rate was 286.4 per 10,000 person-years in the
      earlier period and 146.9 per 10,000 in the later period, a 49.3% (95% confidence
      interval [CI], 16.7%-69.4%) decline. Among participants without diabetes, the age
      and sex-adjusted incidence rate was 84.6 per 10,000 person-years in the earlier
      period and 54.3 per 10,000 person-years in the later period, a 35.4% (95% CI,
      25.3%-45.4%) decline. Hazard ratios for diabetes as a predictor of incident CVD
      were not different in the earlier vs later periods. CONCLUSIONS: We report a 50%
      reduction in the rate of incident CVD events among adults with diabetes, although
      the absolute risk of CVD is 2-fold greater than among persons without diabetes.
      Adults with and without diabetes have benefited similarly during the decline in
      CVD rates over the last several decades. More aggressive treatment of CVD risk
      factors and further research on diabetes-specific factors contributing to CVD
      risk are needed to further reduce the high absolute risk of CVD still experienced
      by persons with diabetes.

PMID- 15562130
TI  - Ownership and use of tissue specimens for research.
AB  - Academic and industrial scientists have sharply increased their demand for
      properly prepared and clinically annotated tissue samples that yield valuable
      insights into the origins and expressions of human disease. Historically,
      research on human tissue samples has been relatively unencumbered by federal
      regulations and occurred without delineation of ownership rights to the
      specimens, patient data, or research products. As regulations have become
      increasingly restrictive, and because clear ownership interests have never been
      established, the presumed right of researchers and institutions to collect, use,
      and dispose of specimens and their associated patient data has remained undefined
      and occasionally contentious. Recent examination of these issues by a US federal
      court resulted in a ruling that individuals do not retain rights of ownership or
      control of biological materials contributed for research, regardless of whether
      commercial benefit accrues. This article examines the legal, regulatory, and
      ethical framework within which human tissue research is currently conducted. We
      contend that because the benefits of medical knowledge derived from tissue
      research potentially accrue to all individuals and future generations (rather
      than a single recipient), society may justify an expansive use of these valuable
      resources for future studies.

PMID- 15562131
TI  - A 69-year-old woman with left main coronary artery disease.

PMID- 15562132
TI  - A 15-month-old child with recurrent otitis media, 2 years later.

PMID- 15562133
TI  - Shared medical decision making: problems, process, progress.

PMID- 15562134
TI  - Obesity and atrial fibrillation: is one epidemic feeding the other?

PMID- 15562135
TI  - JAMA patient page. Coronary artery disease.

PMID- 15562136
TI  - Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting.
AB  - OBJECTIVE: To evaluate the safety and efficacy of aprepitant in the prevention of
      acute and delayed chemotherapy-induced nausea and vomiting (CINV). DATA SOURCES:
      MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using
      the following search terms: aprepitant, Emend, substance P, neurokinin-1,
      chemotherapy, nausea, vomiting, L-754,030, and MK-869. STUDY SELECTION AND DATA
      EXTRACTION: Large, randomized Phase II and III clinical trials examining the use
      of aprepitant for CINV, as well as all published drug interaction studies with
      aprepitant, were included and reviewed. Data lacking in published trials were
      supplemented with the manufacturer product information. DATA SYNTHESIS: The
      pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on
      the results of published clinical trials, aprepitant appears to augment the
      effects of corticosteroids and 5-HT3 antagonists when given prior to highly
      emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most
      benefit in the prevention of delayed CINV and in preventing emesis rather than
      nausea. Data in pediatric patients, patients undergoing stem-cell
      transplantation, and those receiving multiple-day or moderately emetogenic
      chemotherapy are lacking. Common adverse effects are limited to hiccups,
      asthenia, and diarrhea. More serious but rare adverse effects include
      neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and
      inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted.
      CONCLUSIONS: Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5
      HT3 antagonist appears to provide improved efficacy in the prevention of emesis
      in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism
      of action and demonstrated efficacy in this combination, aprepitant should be
      considered for formulary addition.

PMID- 15562137
TI  - Implications of pharmaceutical industry funding on clinical research.
AB  - This commentary explores the influence of industry funding and offers suggestions
      for overcoming some of the problems. First, it is difficult to obtain funding
      from some sources for research with limited commercial value. Second, lack of
      communication among researchers can impede scientific progress. Stopping research
      before meaningful results are available is another area of concern. Next,
      suppressed or delayed publication of data may bias the results of meta-analyses,
      resulting in incorrect risk-benefit profiles for drugs. Finally, commercially
      funded clinical research is more likely to yield positive results than when
      funding comes from other sources. Possible solutions are explored.

PMID- 15562138
TI  - Acute rhabdomyolysis associated with ofloxacin/levofloxacin therapy.
AB  - OBJECTIVE: To report a case of ofloxacin/levofloxacin-induced rhabdomyolysis and
      to compare other reported cases from the literature. CASE SUMMARY: A 19-year-old
      male patient developed ofloxacin/levofloxacin-induced rhabdomyolysis during
      admission for periorbital cellulitis. Symptoms of myalgia, weakness, and swelling
      of the arms developed after 3 days of treatment with ofloxacin 800 mg/day.
      Laboratory analysis confirmed the presence of urine myoglobin (381.2 microg/L)
      and a marked increase in serum myoglobin (590.8 microg/L), along with marked
      elevations in serum creatine kinase (up to 16 546 IU/L). DISCUSSION: In addition
      to ruling out other possible etiologic factors one by one, we assessed the
      probability of ofloxacin/levofloxacin-induced rhabdomyolysis by observing the
      close time relationship between drug administration and the development of
      symptoms/signs, as well as the close time relationship between drug withdrawal
      and the disappearance of symptoms/signs. An objective causality assessment by use
      of the Naranjo probability scale revealed that the adverse drug reaction was
      probable. CONCLUSIONS: Although ofloxacin/levofloxacin-induced rhabdomyolysis
      appears to be rare, patients with muscle pain, swelling, or weakness during
      therapy should be closely monitored for this adverse effect.

PMID- 15562139
TI  - Use of macrolides and tetracyclines for chronic inflammatory diseases.
AB  - OBJECTIVE: To review the efficacy of macrolides and tetracyclines in several
      chronic inflammatory conditions. DATA SOURCES: Searches of MEDLINE (1966-March
      2004) and an extensive bibliography search were undertaken. Key terms included
      acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis,
      rosacea, and rheumatoid arthritis. STUDY SELECTION AND DATA EXTRACTION: Data were
      obtained primarily from randomized placebo-controlled trials upon which key
      recommendations are based. DATA SYNTHESIS: Antibiotics are often prescribed for
      months or even years for treatment of chronic inflammatory conditions such as
      acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis,
      rosacea, and rheumatoid arthritis. Randomized controlled trials have shown that
      azithromycin is useful in the management of cystic fibrosis and the tetracyclines
      are beneficial in the management of rheumatoid arthritis, acne, blepharitis, and
      periodontitis. Several large, randomized controlled trials have failed to show
      any benefit of macrolides in the secondary prevention of cardiovascular disease.
      No randomized placebo-controlled clinical trials have been performed to assess
      the efficacy of macrolides or tetracyclines in patients with rosacea.
      CONCLUSIONS: The use of tetracyclines and macrolides for rosacea is based
      primarily on anecdotal reports or open-label trials. Limited clinical trials
      support the use of tetracyclines or macrolides in acne, blepharitis,
      periodontitis, rheumatoid arthritis, and cystic fibrosis. Trials to date do not
      support the use of antibiotics for secondary prevention of cardiovascular
      disease.

PMID- 15562140
TI  - Use of selective serotonin-reuptake inhibitors in the treatment of depression in
      adults with HIV.
AB  - OBJECTIVE: To review the safety and efficacy of selective serotonin-reuptake
      inhibitors (SSRIs) for the treatment of depression in adults with HIV. DATA
      SOURCES: We searched Pre-MEDLINE and MEDLINE (1966-May 2004) using terms
      including generic names of antidepressants and antiretrovirals, depression, HIV,
      and acquired immunodeficiency syndrome. All English-language articles were
      included in this review. DATA SYNTHESIS: SSRIs may be effective and better
      tolerated than tricyclic antidepressants in HIV-positive adults. SSRIs did not
      appear to affect CD4+ cell counts. CONCLUSIONS: Controlled trials comparing SSRIs
      are lacking; thus, it is difficult to determine whether one SSRI is more
      efficacious than another. It appears that most SSRIs may be used in HIV-positive
      adults. If drug-drug interactions are a concern, sertraline, citalopram, and
      possibly escitalopram may be considered.

PMID- 15562141
TI  - Incretin mimetics as emerging treatments for type 2 diabetes.
AB  - OBJECTIVE: To review the physiology, pharmacology, and clinical efficacy of
      glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide
      in clinical studies. DATA SOURCES: Primary literature obtained via MEDLINE (1966
      April 2004) and International Pharmaceutical Abstracts (1970-April 2004)
      searches; abstracts obtained from meeting sources and manufacturers. STUDY
      SELECTION AND DATA EXTRACTION: All English-language studies and abstracts
      evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with
      type 2 diabetes were reviewed. Data from animal studies were also included if
      human data were not available. Primary and review articles related to the
      physiology, development, and evaluation of GLP-1s were reviewed. DATA SYNTHESIS:
      GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin
      mimetics that have been shown in human studies to be an effective treatment to
      improve glycemic control in patients with type 2 diabetes. Mechanisms by which
      these compounds improve glycemic control include enhancing glucose-dependent
      pancreatic secretion of insulin in response to nutrient intake, inhibiting
      glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1
      has been shown to promote pancreatic progenitor cell differentiation and improve
      beta-cell function and lifespan. Reported adverse effects of exenatide and
      liraglutide include nausea, vomiting, and transient headache, as well as
      increased risk of hypoglycemia when used with sulfonylureas. CONCLUSIONS:
      Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic
      control for patients with type 2 diabetes through unique mechanisms not available
      with current pharmaceutical products. Ongoing Phase III studies will help to
      further position these compounds as treatment options for patients with type 2
      diabetes.

PMID- 15562142
TI  - Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and
      chronic bronchial infection with Pseudomonas aeruginosa.
AB  - BACKGROUND: Non-cystic fibrosis (CF) patients with bronchiectasis usually develop
      chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to
      worsening lung function and increased morbidity and mortality. OBJECTIVE: To
      determine whether direct aerosol delivery of tobramycin to the lower airways may
      control infection and produce only low systemic toxicity. METHODS: A double
      blind, placebo-controlled crossover trial involving 30 patients was conducted to
      determine the clinical effectiveness and safety of 6-month tobramycin inhalation
      therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice
      daily in 2 cycles, each for 6 months, with a one-month washout period. The number
      of exacerbations, number of hospital admissions, number of hospital admission
      days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity,
      density of PA in sputum, emergence of bacterial resistance, and emergence of
      other opportunistic bacteria were recorded. RESULTS: The number of admissions and
      days of admission (mean +/- SD) during the tobramycin period (0.15 +/- 0.37 and
      2.05 +/- 5.03) were lower than those during the placebo period (0.75 +/-1.16 and
      12.65 +/- 21.8) (p < 0.047). A decrease in PA density in sputum was associated
      with tobramycin administration in the analysis of the first 6-month cycle (p =
      0.038). No significant differences were observed in the number of exacerbations,
      antibiotic use, pulmonary function, and quality of life. The emergence of
      bacterial resistance and other bacteria did not differ between the 2 periods of
      study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not
      with detectable ototoxicity or nephrotoxicity. CONCLUSIONS: Aerosol
      administration of high-dose tobramycin in non-CF bronchiectatic patients for
      endobronchial infection with PA appears to be safe and decreases the risk of
      hospitalization and PA density in sputum. Nevertheless, pulmonary function and
      quality of life are not improved, and the risk of bronchospasm is appreciable.

PMID- 15562143
TI  - Pharmacologic prevention or delay of type 2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the current data on pharmacologic interventions intended
      to prevent or delay the onset of type 2 diabetes mellitus. DATA SOURCES: Searches
      of MEDLINE (1966-July 2002) and an extensive manual review of journals were
      performed using the key search terms diabetes mellitus, metformin, acarbose,
      troglitazone, orlistat, nateglinide, risk reduction, and prevention. STUDY
      SELECTION AND DATA EXTRACTION: All articles identified from the data sources were
      evaluated, and all information deemed relevant was included for this review.
      Randomized controlled trials and meta-analyses were included if the primary
      outcome measure was prevention of diabetes and/or change in the rate of
      progression to diabetes. DATA SYNTHESIS: Type 2 diabetes mellitus is a growing
      epidemic. Major risk factors include obesity, impaired glucose tolerance, and
      impaired fasting glucose. Complications of diabetes result in significant
      morbidity and mortality and are a substantial public health issue. Four
      randomized, blinded, controlled trials have assessed the efficacy of different
      medications, including metformin, troglitazone, acarbose, and orlistat, at
      decreasing the risk of progression to diabetes in patients at risk for developing
      diabetes. All of these agents decreased the risk of progression to diabetes.
      CONCLUSIONS: Metformin, troglitazone, acarbose, and orlistat have been shown to
      decrease the risk of progression to diabetes in patients at risk for developing
      diabetes. Other questions that address issues such as identifying target
      populations, cost-effectiveness, and screening strategies must be answered to
      more fully define the place of pharmacologic therapy to prevent or delay
      diabetes.

PMID- 15562144
TI  - Multiple complications and withdrawal syndrome associated with
      quetiapine/venlafaxine intoxication.
AB  - OBJECTIVE: To report a case of quetiapine/venlafaxine intoxication associated
      with multiple complications and to review their possible relationship with these
      2 drugs. CASE SUMMARY: A 53-year-old white man was admitted to the hospital for
      loss of consciousness secondary to voluntary intoxication with venlafaxine and
      quetiapine. Several complications were attributable to this intoxication
      including seizures, prolonged coma, respiratory depression, neuroleptic malignant
      syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal
      syndrome. DISCUSSION: Quetiapine could be responsible for the neuroleptic
      malignant syndrome presented in this case. Moreover, venlafaxine intoxication,
      fever, autonomic instability, and myoclonus presented serotonin syndrome as a
      differential diagnosis. Potential causes of seizures and prolongation of the QRS
      and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine
      withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics
      of drug elimination in the context of intoxication. CONCLUSIONS: Clinicians
      should be aware of possible complications following intoxication with atypical
      antipsychotics and anti-depressants, including protracted altered mental status.

PMID- 15562145
TI  - Traumatic tear of tibialis anterior during a Gaelic football game: a case report.
AB  - Reports of traumatic injury to the anterior lower leg muscles are scarce, with
      only a handful of reports of traumatic injury to the tibialis anterior. A
      database search of Medline, Cinhal, and Sports Discus only revealed three such
      cases, and they did not result from a direct sporting injury. This report
      documents the case of a traumatic rupture of tibialis anterior muscle in a young
      female Gaelic football player. It details the surgical repair and management of
      tibialis anterior muscle and the physiotherapy rehabilitation to full function.

PMID- 15562146
TI  - Unusual stress fractures of the proximal phalanx of the great toe: a report of
      two cases.
AB  - Stress fractures of the toes are rare. Most reported fractures of the proximal
      phalanx of the great toe have been associated with halux valgus deformity. Two
      cases are presented that illustrate several unique features of this rare injury
      which have not been reported before. One of the cases went on to non-union,
      requiring bone grafting and internal fixation.

PMID- 15562147
TI  - Paraplegia secondary to fracture-subluxation of the thoracic spine sustained
      playing rugby union football.
AB  - Fractures of the spinal column during rugby matches of all codes are rare but
      catastrophic, especially when associated with spinal cord injury. The cervical
      spine is vulnerable during trauma to the head and neck in contact sports. Spinal
      injuries reported during rugby matches have almost exclusively involved the
      cervical region, often with neurological sequelae. This is the first reported
      case of paraplegia caused by a fracture-dislocation of the thoracic spine
      resulting from a low velocity rugby union injury.

PMID- 15562148
TI  - Bridging osteophyte of the anterosuperior sacroiliac joint as a cause of lumbar
      back pain.
AB  - A case report is presented of a patient with an anterosuperior osteophytic bone
      bridge of the sacroiliac joint causing lumbar back pain. After prolonged
      physiotherapy, the bone bridge was excised, with complete resolution of the
      symptoms. Excision should only be considered in cases of symptomatic sacroiliac
      joint pain that does not respond to rehabilitation programmes and conservative
      treatment.

PMID- 15562149
TI  - Unusual cause of wrist pain in a golfer.
AB  - Wrist injury is common in golfers and normally occurs at the impact of the club
      with the ball. The unusual case is reported of a low handicap golfer with wrist
      pain aggravated by the putting stroke. The condition was resolved with treatment.
      The likely mechanism for the injury is discussed.

PMID- 15562150
TI  - Half pipe snowboarding: an (un)forgettable experience or an increasing risk for
      head injury?
AB  - The case is presented of a professional half pipe snowboarder with a large post
      traumatic subdural haematoma, which allowed close to normal functioning and
      socialisation. It is an example of a potentially life threatening sports injury
      in an increasingly commercialised and popular winter sport. It highlights that a
      knowledge of injury patterns and a high level of suspicion should be maintained
      in the treatment of snowboarding injuries.

PMID- 15562151
TI  - Pulmonary oedema precipitated by cold water swimming.
AB  - The case is reported of a physically fit man, who, while training for a
      triathlon, developed pulmonary oedema secondary to swimming in cold water.
      Pulmonary oedema is usually caused by a combination of exercise and cold water,
      resulting in an increase in cardiac preload and after load, which causes an
      increase in pulmonary capillary pressure. Most cases improve spontaneously and
      quickly with no recurrence of symptoms.

PMID- 15562152
TI  - Endurance exercise and the production of growth hormone and haematopoietic
      factors in patients with anaemia.
AB  - BACKGROUND: Physical activity has been shown to stimulate haematopoiesis in
      patients with anaemia due to chronic renal failure or haematological
      malignancies. OBJECTIVE: To evaluate the effect of moderate exercise on the
      production of haematopoietically active factors. METHODS: Ten patients (four men
      and six women, mean (SD) age 51 (10) years) with a haemoglobin concentration
      under 130 g/l (men) or 120 g/l (women) carried out five three minute exercise
      bouts at an intensity of 80% of the maximal heart rate, corresponding to a
      lactate concentration of 3 (0.5) mmol/l. Patients rested for three minutes
      between bouts. The concentrations of interleukin 6, stem cell factor, granulocyte
      monocyte colony stimulating factor, granulocyte colony stimulating factor,
      erythropoietin, and growth hormone (GH) were evaluated before and in the eight
      hours after exercise. RESULTS: GH had risen significantly 15 minutes after
      exercise (1.1 (1.3) v 2.7 (2.8) ng/ml; p<0.05). No change in the concentration of
      the other cytokines and growth factors was observed in the eight hours after
      exercise. CONCLUSIONS: In patients with anaemia, submaximal exercise does not
      affect the concentration of haematopoietically active cytokines. However, it
      leads to an increased concentration of GH. This may be responsible for the
      improved haematopoiesis observed after an exercise programme in patients with
      chronic diseases.

PMID- 15562153
TI  - Soleus accessorius, an anomalous muscle in a young athlete: case report and
      analysis of the literature.
AB  - The soleus accessory muscle is a rare anatomical variation. It usually appears as
      a soft tissue mass and may be mistaken for a tumour or an inflammatory lesion.
      The differential diagnoses include ganglion, lipoma, haemangioma, synovioma, and
      sarcoma. This is a report of such a muscle mass in the leg of a young athlete
      with 16 years follow up. A review of the English literature on this subject is
      also presented.

PMID- 15562154
TI  - Pursuing the dream.

PMID- 15562155
TI  - Why we should allow performance enhancing drugs in sport.

PMID- 15562156
TI  - Sudden death risk in older athletes: increasing the denominator.

PMID- 15562157
TI  - Reactive oxygen species and tendinopathy: do they matter?

PMID- 15562158
TI  - Cyriax physiotherapy for tennis elbow/lateral epicondylitis.
AB  - Tennis elbow or lateral epicondylitis is one of the most common lesions of the
      arm with a well defined clinical presentation, which significantly impacts on the
      community. Many treatment approaches have been proposed to manage this condition.
      One is Cyriax physiotherapy. The effectiveness and reported effects of this
      intervention are reviewed.

PMID- 15562159
TI  - Blood borne infections in sport: risks of transmission, methods of prevention,
      and recommendations for hepatitis B vaccination.
AB  - Athletes are at risk of blood borne infections through bleeding injuries or
      injection of drugs with contaminated syringes. Prevention should focus on
      reducing non-sport associated risky behaviour, as well as dealing appropriately
      with bleeding injuries. The risk of transmission of hepatitis B virus is
      particularly high in athletes in contact and collision sports, those who live in
      or travel to endemic regions, injecting drug abusers, and those who practice
      first aid when there is no healthcare practitioner available. It is recommended
      that such athletes, and also adolescent athletes, should be vaccinated against
      the virus as a routine.

PMID- 15562160
TI  - Perception of Nigerian athletes of the use of mouth guards to prevent the
      stresses of sports injury.
AB  - OBJECTIVE: The perception of Nigerian athletes of the use of mouth guards to
      prevent the stresses of sports injuries was examined using psychological,
      sociological, and physical stress variables. METHODS: The descriptive survey
      research design was used in this study. Participants (n = 333) were selected
      using the purposive random sampling technique and data were collected using the 4
      point Likert type instrument. The coefficient alpha was used to determine the
      reliability of the instrument with r = 0.79 for psychological, r = 0.66 for
      physical, and r = 0.74 for sociological stress. RESULTS: The result reveals that
      female athletes perceived the use of mouth guards as being more important to
      prevent the stresses of sports injuries than male athletes, while athletes who
      had used mouth guards for longer periods also perceived them as being more
      important to prevent the stresses of sports injuries compared to those who had
      used them less. The result also revealed a significant difference (p<0.05) among
      the various sport groups as independent variables on the psychological and
      physical stress variables. Scheffe post hoc analysis was used to identify the
      group where significant difference was found. CONCLUSIONS: The study concluded
      that since the impact of injury is perceived to affect the cognitive function of
      athletes, athletes should be educated on the use of mouth guards in order to
      reduce the incidence of oral and dental injuries to the barest minimum.

PMID- 15562161
TI  - Mechanisms of head injuries in elite football.
AB  - OBJECTIVES: The aim of this study was to describe, using video analysis, the
      mechanisms of head injuries and of incidents with a high risk of head injury in
      elite football. METHODS: Videotapes and injury information were collected
      prospectively for 313 of the 409 matches played in the Norwegian (2000 season)
      and Icelandic (1999 and 2000 season) professional leagues. Video recordings of
      incidents where a player appeared to be hit in the head and the match was
      consequently interrupted by the referee were analysed and cross referenced with
      reports of acute time loss injuries from the team medical staff. RESULTS: The
      video analysis revealed 192 incidents (18.8 per 1000 player hours). Of the 297
      acute injuries reported, 17 (6%) were head injuries, which corresponds to an
      incidence of 1.7 per 1000 player hours (concussion incidence 0.5 per 1000 player
      hours). The most common playing action was a heading duel with 112 cases (58%).
      The body part that hit the injured player's head was the elbow/arm/hand in 79
      cases (41%), the head in 62 cases (32%), and the foot in 25 cases (13%). In 67 of
      the elbow/arm/hand impacts, the upper arm of the player causing the incident was
      at or above shoulder level, and the arm use was considered to be active in 61
      incidents (77%) and intentional in 16 incidents (20%). CONCLUSIONS: This study
      suggests that video analysis provides detailed information about the mechanisms
      for head injuries in football. The most frequent injury mechanism was elbow to
      head contact, followed by head to head contact in heading duels. In the majority
      of the elbow to head incidents, the elbow was used actively at or above shoulder
      level, and stricter rule enforcement or even changes in the laws of the game
      concerning elbow use should perhaps be considered, in order to reduce the risk of
      head injury.

PMID- 15562162
TI  - Skeletal muscle pathology in endurance athletes with acquired training
      intolerance.
AB  - BACKGROUND: It is well established that prolonged, exhaustive endurance exercise
      is capable of inducing skeletal muscle damage and temporary impairment of muscle
      function. Although skeletal muscle has a remarkable capacity for repair and
      adaptation, this may be limited, ultimately resulting in an accumulation of
      chronic skeletal muscle pathology. Case studies have alluded to an association
      between long term, high volume endurance training and racing, acquired training
      intolerance, and chronic skeletal muscle pathology. OBJECTIVE: To systematically
      compare the skeletal muscle structural and ultrastructural status of endurance
      athletes with acquired training intolerance (ATI group) with asymptomatic
      endurance athletes matched for age and years of endurance training (CON group).
      METHODS: Histological and electron microscopic analyses were carried out on a
      biopsy sample of the vastus lateralis from 18 ATI and 17 CON endurance athletes.
      The presence of structural and ultrastructural disruptions was compared between
      the two groups of athletes. RESULTS: Significantly more athletes in the ATI group
      than in the CON group presented with fibre size variation (15 v 6; p = 0.006),
      internal nuclei (9 v 2; p = 0.03), and z disc streaming (6 v 0; p = 0.02).
      CONCLUSIONS: There is an association between increased skeletal muscle
      disruptions and acquired training intolerance in endurance athletes. Further
      studies are required to determine the nature of this association and the possible
      mechanisms involved.

PMID- 15562163
TI  - Abnormally high serum ferritin levels among professional road cyclists.
AB  - BACKGROUND: An international, longitudinal medical follow up examination of male
      professional road cyclists revealed excessively elevated serum ferritin levels.
      OBJECTIVE: To evaluate the importance of elevated ferritin values among
      professional cyclists, their relationship with age and nationality, and their
      evolution over 3 years. METHODS: Over 1000 serum ferritin values were collected.
      Other parameters were included in order to exclude conditions which might have
      increased ferritin levels without changing body iron stores. RESULTS: In 1999,
      over 45% of riders displayed ferritin values above 300 ng/ml and one fourth
      levels over 500 ng/ml. These percentages had decreased to 27% and 9%,
      respectively, 3 years later, while the overall average, which was above the
      normal limits in 1999, had decreased by 33% in 3 years. Older cyclists had higher
      ferritin values than younger cyclists. There was also a relationship between
      ferritin levels and the nationality of the cyclists. Analysis of 714 riders in
      2000 and 2002 showed only a slight and insignificant decrease in the mean
      ferritin value although those with initially elevated iron stores had a much
      greater decrease. CONCLUSION: Professional road cyclists used excessive iron
      supplementation leading to high serum ferritin levels correlating with increased
      body iron stores. Although the situation progressively improved over 3 years, it
      remains worrying as increased body iron stores are related to health
      complications. Therefore, prevention in addition to the fight against doping
      should be a main goal of the UCI. Aggressive therapy for athletes with excessive
      ferritin values should be carried out at or before the end of their careers.

PMID- 15562164
TI  - Histology of the fascial-periosteal interface in lower limb chronic deep
      posterior compartment syndrome.
AB  - OBJECTIVE: To describe the histological features of the fascial-periosteal
      interface at the medial tibial border of patients surgically treated for chronic
      deep posterior compartment syndrome and to make statistical comparisons with
      control tissue. METHODS: Nineteen subjects and 11 controls were recruited.
      Subject tissue was obtained at operation, and control tissue from autopsy cases.
      Tissue samples underwent histological preparation and then examination by an
      independent pathologist. Samples were analysed with regard to six histological
      variables: fibroblastic activity, chronic inflammatory cells, vascularity,
      collagen regularity, mononuclear cells, and ground substance. Collagen regularity
      was measured with respect to collagen density, fibre arrangement, orientation,
      and spacing. The observed changes were graded from 1 to 4 in terms of
      abnormality. Mann-Whitney U test, Spearman correlation coefficients, and
      intraobserver reliability scores were used. RESULTS: With regard to collagen
      arrangement, control tissue showed greater degrees of irregularity than subject
      tissue (p = 0.01). Subjects with a symptom duration of greater than 12 months (as
      opposed to less than 12 months) showed greater degrees of collagen irregularity
      (p = 0.043). Vascular changes approached significance (p = 0.077). With regard to
      the amount of fibrocyte activity, chronic inflammatory cell activity, mononuclear
      cells, or ground substance, there were no significant differences between
      controls and subjects. Good correlation was seen in scores measuring chronic
      inflammatory cell activity and mononuclear cells (r = 0.649), and moderate
      correlation was seen between fibrocyte activity and vascular changes (r = 0.574).
      Intraobserver reliability scores were good for chronic inflammatory cell activity
      and moderate for vascular changes, but were poor for collagen and fibrocyte
      variables. Individual cases showed varying degrees of fibrocyte activity, chronic
      inflammatory cellular infiltration, vascular abnormalities, and collagen fibre
      disruption. CONCLUSIONS: Statistical analysis showed no histological differences
      at the fascial-periosteal interface in cases of chronic deep posterior
      compartment syndrome, except for collagen, which showed less irregularity in
      subject samples. The latter may indicate a remodelling process, and this is
      supported by greater collagen irregularity in subjects with longer duration of
      symptoms.

PMID- 15562165
TI  - Weight changes, medical complications, and performance during an Ironman
      triathlon.
AB  - BACKGROUND: Subjects exercising without fluid ingestion in desert heat terminated
      exercise when the total loss in body weight exceeded 7%. It is not known if
      athletes competing in cooler conditions with free access to fluid terminate
      exercise at similar levels of weight loss. OBJECTIVES: To determine any
      associations between percentage weight losses during a 224 km Ironman triathlon,
      serum sodium concentrations and rectal temperatures after the race, and
      prevalence of medical diagnoses. METHODS: Athletes competing in the 2000 and 2001
      South African Ironman triathlon were weighed on the day of registration and again
      immediately before and immediately after the race. Blood pressure and serum
      sodium concentrations were measured at registration and immediately after the
      race. Rectal temperatures were also measured after the race, at which time all
      athletes were medically examined. Athletes were assigned to one of three groups
      according to percentage weight loss during the race. RESULTS: Body weight was
      significantly (p<0.0001) reduced after the race in all three groups. Serum sodium
      concentrations were significantly (p<0.001) higher in athletes with the greatest
      percentage weight loss. Rectal temperatures were the same in all groups, with
      only a weak inverse association between temperature and percentage weight loss.
      There were no significant differences in diagnostic indices of high weight loss
      or incidence of medical diagnoses between groups. CONCLUSIONS: Large changes in
      body weight during a triathlon were not associated with a greater prevalence of
      medical complications or higher rectal temperatures but were associated with
      higher serum sodium concentrations.

PMID- 15562167
TI  - Sensory level electrical muscle stimulation: effect on markers of muscle injury.
AB  - BACKGROUND: Monophasic high voltage stimulation (MHVS) is widely prescribed for
      the treatment of inflammation associated with muscle injury. However, limited
      scientific evidence exists to support its purported benefits in humans.
      OBJECTIVE: To examine the efficacy of early initiation of MHVS treatment after
      muscle injury. METHODS: In a randomised, cross over design, 14 men performed
      repetitive eccentric contractions of the elbow flexor muscles followed by either
      MHVS or control treatment. MHVS treatments were applied five minutes and 3, 6,
      24, 48, 72, 96, and 120 hours after eccentric contractions. RESULTS: MHVS
      resulted in a significant reduction (p<0.05) in delayed onset muscle soreness 24
      hours after eccentric exercise compared with controls. Elbow extension was
      significantly increased immediately after administration of MHVS compared with
      controls. No significant differences were observed between MHVS treatment and
      controls for maximal isometric strength, flexed arm angle, or arm volume.
      CONCLUSIONS: Early and frequent application of MHVS may provide transient relief
      from delayed onset muscle soreness and short term improvements in range of motion
      after injurious exercise. However, MHVS treatment may not enhance recovery after
      muscle injury because of lack of improvements in strength and active range of
      motion.

PMID- 15562168
TI  - Inspiratory resistive loading improves cycling capacity: a placebo controlled
      trial.
AB  - BACKGROUND: Respiratory muscle training has been shown to improve both its
      strength and endurance. The effect of these improvements on whole-body exercise
      performance remains controversial. OBJECTIVE: To assess the effect of a 10 week
      inspiratory resistive loading (IRL) intervention on respiratory muscle
      performance and whole-body exercise endurance. METHODS: Fifteen apparently
      healthy subjects (10 men, 5 women) were randomly allocated to one of three
      groups. One group underwent IRL set at 80% of maximum inspiratory pressure with
      ever decreasing work/rest ratios until task failure, for three days a week for 10
      weeks (IRL group). A second placebo group performed the same training procedure
      but with a minimal resistance (PLA group). IRL and placebo training were
      performed at rest. The remaining five control subjects performed no IRL during
      the 10 week study period (CON group). Cycling endurance capacity at 75% VO(2)peak
      was measured before and after the intervention. RESULTS: After the 10 week IRL
      intervention, respiratory muscle strength (maximum inspiratory pressure) and
      endurance (sum of sustained maximum inspiratory pressure) had significantly
      improved (by 34% and 38% respectively). An increase in diaphragm thickness was
      also observed. These improvements translated into a 36% increase in cycling time
      to exhaustion at 75% VO(2)peak. During cycling trials, heart rate, ventilation,
      and rating of perceived exertion were attenuated in the IRL group. No changes
      were observed for the PLA or CON group either in the time to exhaustion or
      cardiorespiratory response to the same intensity of exercise. CONCLUSION: Ten
      weeks of IRL attenuated the heart rate, ventilatory, and perceptual response to
      constant workload exercise, and improved the cycling time to exhaustion.
      Familiarisation was not a factor and the placebo effect was minimal.

PMID- 15562169
TI  - Comparing spondylolysis in cricketers and soccer players.
AB  - OBJECTIVE: To determine whether the location of spondylolysis in the lumbar spine
      of athletes differs with biomechanical factors. METHODS: Single photon emission
      computerised tomography and reverse gantry computerised tomography were used to
      investigate 42 cricketers and 28 soccer players with activity related low back
      pain. Sites of increased scintigraphic uptake in the posterior elements of the
      lumbar spine and complete or incomplete fracture in the pars interarticularis
      were compared for these two sports. RESULTS: Thirty seven (90.4%) cricketers and
      23 (82.1%) soccer players studied had sites of increased uptake. In cricketers,
      these sites were on the left of the neural arch of 49 lumbar vertebrae and on the
      right of 33 vertebrae. In soccer players there was a significantly different
      proportion, with 17 sites on the left and 28 on the right (difference of 22.0%;
      95% confidence interval (CI) 0.04 to 0.38). Lower lumbar levels showed increased
      scintigraphic uptake more frequently than did higher levels, although the trend
      was reversed at L3 and L4 in soccer. Forty spondylolyses were identified in the
      lumbar vertebrae of the cricketers and 35 spondylolyses in the soccer players.
      These comprised 26 complete and 14 incomplete fractures in the cricketers, and 25
      complete and 10 incomplete fractures in the soccer players. Similar numbers of
      incomplete fractures were found either side of the neural arch in soccer players,
      but there were more incomplete fractures in the left pars (14) than in the right
      (2) in cricketers. The proportion of incomplete fractures either side of the
      neural arch was significantly different between cricket players and soccer
      players (difference of 37.5%; 95% CI 0.02 to 0.65). Most complete fractures were
      at L5 (66.7%) and more were found at L3 (15.7%) than L4 (6.9%). However,
      incomplete fractures were more evenly spread though the lower three lumbar levels
      with 41.7% at L5, 37.5% at L4, and 20.8% at L3. CONCLUSIONS: Fast bowling in
      cricket is associated with pars interarticularis bone stress response and with
      development of incomplete stress fractures that occur more frequently on the left
      than the right. Playing soccer is associated with a more symmetrical distribution
      of bone stress response, including stress fracturing. Within cricketers,
      unilateral spondylolyses tend to arise on the contralateral side to the bowling
      arm.

PMID- 15562171
TI  - Reductions in pre-season training loads reduce training injury rates in rugby
      league players.
AB  - OBJECTIVES: To investigate if reductions in pre-season training loads reduced the
      incidence of training injuries in rugby league players, and to determine if the
      reductions in training loads compromised the improvements in physical fitness
      obtained during the pre-season preparation period. METHODS: A total of 220 sub
      elite rugby league players participated in this 3 year prospective study. Players
      underwent measurements of speed, muscular power, and maximal aerobic power before
      and after three 4 month (December to March) pre-season preparation periods (2001
      2003). A periodised skills and conditioning program was implemented, with
      training loads progressively increased in the general preparatory phase of the
      season (December to February) and reduced slightly in March in preparation for
      the competitive phase of the season. Training loads were calculated by
      multiplying the training session intensity by the duration of the training
      session. Following the initial season (2001), training loads were reduced through
      reductions in training duration (2002) and training intensity (2003). The
      incidence of injury was prospectively recorded over the three pre-season periods.
      RESULTS: The training loads for the 2002 and 2003 pre-season periods were
      significantly lower (p<0.001) than those in 2001. The incidence of injury was
      significantly higher in the 2001 pre-season than the 2002 and 2003 pre-season
      periods. The increases in maximal aerobic power progressively improved across the
      three seasons with a 62-88% probability that the 2002 and 2003 pre-season
      improvements in maximal aerobic power were of greater physiological significance
      than the 2001 pre-season improvements in maximal aerobic power. CONCLUSIONS:
      These findings demonstrate that reductions in pre-season training loads reduce
      training injury rates in rugby league players and result in greater improvements
      in maximal aerobic power.

PMID- 15562172
TI  - Sports related maxillofacial injuries: the first maxillofacial trauma database in
      Switzerland.
AB  - BACKGROUND: With the increase in the amount of medical data handled by emergency
      units, advances in computerisation have become necessary. New computer technology
      should have a major influence on accident analysis and prevention and the quality
      of research in the future. OBJECTIVES: To investigate the occurrence of sports
      related maxillofacial injuries using a newly installed relational database. To
      establish the first sports trauma database in Switzerland. METHODS: The Qualicare
      databank was used to prospectively review 57 248 case histories of patients
      treated in the Department of Emergency Medicine between January 2000 and December
      2002. Pre-defined key words were used to collect data on sports related
      maxillofacial injuries. RESULTS: A total of 750 patients with maxillofacial
      injuries were identified. Ninety (12%) were sports related maxillofacial
      fractures. Most (27%) were sustained during skiing and snowboarding, 22% during
      team sports such as soccer or ice hockey, and 21% were from cycling accidents.
      Sixty eight per cent of the cyclists, 50% of the ice hockey players and soccer
      players, and 48% of the skiers and snowboarders had isolated fractures of the
      midface. Fractures of the mandible were noted predominantly in contact sports.
      CONCLUSIONS: Computerisation of trauma and emergency units and the introduction
      of customised software can significantly reduce the workload of researchers and
      doctors. The effective use of new computer technology should have a considerable
      influence on research and the quality of future prospective and retrospective
      studies.

PMID- 15562174
TI  - Three year follow up of a self certification system for the assessment of fitness
      to dive in Scotland.
AB  - BACKGROUND: The need for routine medical examinations of sport divers in the
      Scottish Sub-Aqua Club (Scot-SAC) was revised in March 2000, and a new system
      using a self administered screening questionnaire was developed to allow divers
      to be assessed when necessary by doctors with diving medicine experience.
      OBJECTIVE: To assess the effect of the new medical system on medical referee
      workload, diver exclusion rates, and diving incident frequency. METHODS: All
      divers were required to complete a questionnaire to screen for conditions that
      might affect fitness to dive. Divers answering "Yes" to any of the questions had
      their medical background assessed by a diving doctor, and, if necessary, received
      a clinical examination or investigation. The rate of diver exclusions based on
      the questionnaire response was recorded in conjunction with analysis of the
      incident reports. RESULTS: The number of forms requiring review by diving doctors
      increased from 1.2% to 5.7% (p<0.0001, 95% confidence interval (CI) -0.06 to 
      0.03) in the year after the introduction of the new medical system and gradually
      increased in subsequent years to 7.7% (p<0.0001, 95% CI -0.08 to -0.05). The
      number of divers failing to be certified fit to dive increased slightly from 0.7%
      to 1.0% after one year (p = 0.26, 95% CI -0.01 to 0.00) and subsequently to 2.0%
      (p = 0.0003, 95% CI 0.02 to -0.01) after three years. Most divers were certified
      fit to dive on the basis of the questionnaire alone, and only 0.9% required
      objective investigation (such as exercise testing or echocardiography). Analysis
      of the incidents during three years of follow up confirmed that no incident
      occurred because of an undetected pre-existing medical condition. Two incidents
      involved divers with hypertension, but both had received medical examinations and
      investigation based on their responses to the questionnaire. CONCLUSION: The new
      self administered questionnaire system appears to be an effective screening tool
      for the detection of divers requiring detailed assessment by doctors with diving
      medicine experience.

PMID- 15562176
TI  - Patellar tendinosis as an adaptive process: a new hypothesis.
AB  - BACKGROUND: Patellar tendinosis (PT), or "jumper's knee" is a common condition in
      athletes participating in jumping sports, and is characterised by proximal
      patellar tendon pain and focal tenderness to palpation. Hypoechoic lesions
      observed in the proximal patellar tendon associated with the tendinosis are
      typically described as being a result of degenerative change or "failed healing".
      We propose a new model for the development of the hypoechoic lesion observed in
      PT, in which the aetiology is an adaptive response to differential forces within
      the tendon. METHODS: We assessed the clinical, histopathological, and
      biomechanical literature surrounding the patellar tendon and integrated this with
      research into the response of tendons to differential forces. RESULTS AND
      CONCLUSIONS: We propose that the hypoechoic lesion commonly described in PT is
      the result of adaptation or partial adaptation of the proximal patellar tendon to
      a compressive load. We postulate that the biomechanics of the patellar-patellar
      tendon interface creates this compressive environment. Secondary failure of the
      surrounding tensile adapted tendon tissue may result in tissue overload and
      failure, with resultant stimulation of nociceptors. We believe that this
      "adaptive model" of patellar tendinosis is consistent with the clinical and
      histological findings.

PMID- 15562177
TI  - Improving golf performance with a warm up conditioning programme.
AB  - OBJECTIVES: To determine whether a golf specific warm up programme (both
      immediately prior to play and after performing it five times a week for 5 weeks)
      improved performance in 10 male golfers compared with 10 controls matched for
      age, sex, and handicap. METHODS: Twenty male golfers were matched for age (+/-2
      years) and handicap (+/-1 stroke). Club head speed was assessed by two
      dimensional video analysis in a laboratory setting. In week 1, all golfers
      performed 10 strokes. In weeks 2 and 7, the controls underwent the same procedure
      as in week 1. The exercise group performed the golf specific warm up followed by
      their 10 strokes. Between weeks 2 and 7, the exercise group performed the
      specially designed warm up five times a week for 5 weeks. RESULTS: The mean club
      head speeds of the exercise group improved at each testing week. Between weeks 1
      and 2, golfers in the exercise group improved their club head speed on average by
      3-6 m/s (12.8%), and between weeks 1 and 7, they increased their club head speeds
      by 7-10 m/s (24.0%). With the exception of one golfer whose club head speed
      varied by 1.7 m/s, the mean club head speeds of the golfers in the control group
      hardly varied over the testing period (range: 0.3-0.8 m/s). A significant
      difference (p = 0.029) was found between the mean club head speeds of the
      exercise and control groups over the duration of the study, and a significant
      interaction over time (p<0.001) was also found. CONCLUSIONS: This study has shown
      that golfers' performances will be significantly improved by undertaking a golf
      specific warm up programme compared with not performing the warm up.

PMID- 15562178
TI  - Effective ways of restoring muscular imbalances of the rotator cuff muscle group:
      a comparative study of various training methods.
AB  - BACKGROUND: Many studies have compared different training methods for improving
      muscular performance, but more investigations need to be directed to the
      restoration of muscular imbalances. OBJECTIVE: To determine the most effective
      training for altering strength ratios in the shoulder rotator cuff. METHODS:
      Forty eight physical education students were randomly assigned to four groups (12
      per group): (a) experimental group who carried out multijoint dynamic resistance
      training for shoulder internal and external rotation movement (pull ups or lat
      pull downs, overhead press, reverse pull ups, push ups) (MJDR group); (b)
      experimental group who exercised the same muscle group using dumbbells weighing 2
      kg (isolated group); (c) experimental group who followed an isokinetic
      strengthening programme for the rotator cuff muscle group (isokinetic group); (d)
      control group who had no strength training. Testing was performed in the supine
      position with the glenohumeral joint in 90 degrees of abduction in the coronal
      plane, with a range of motion of 0-90 degrees of external rotation and 0-65
      degrees of internal rotation at angular velocities of 60, 120, and 180 degrees
      /s. The test procedure was performed before and after the exercise period of six
      weeks. RESULTS: One way analysis of variance found no differences between the
      groups for the initial tests. Analysis of variance with repeated measures showed
      that the strength ratios in all the experimental groups had altered after the
      exercise period, with the isokinetic group showing the most significant
      improvement. CONCLUSIONS: Isokinetic strengthening is the most effective method
      of altering strength ratios of the rotator cuff muscle.

PMID- 15562179
TI  - Exercise following a sport induced concussion.
AB  - OBJECTIVE: To determine if an athlete's capacity to perform exercise is impaired
      following concussion and whether this would be reflected by an altered heart rate
      response. METHODS: Of the 14 concussed athletes, nine missed playing time as a
      direct result of their concussion and five did not. The concussed athletes
      performed an exercise protocol on a cycle ergometer within 72 hours of being
      asymptomatic at rest and a second test at 5 days following the previous
      assessment. Matched controls (n = 14) were tested using the same time line. The
      exercise protocol consisted of a 2 minute warm up, 10 minute, low-moderate
      intensity, steady state exercise session, and a high intensity interval protocol.
      The interval protocol consisted of a 40 second high intensity bout, followed by a
      40 second rest period. This protocol continued until the participant had reached
      volitional fatigue. RESULTS: The number of exercise bouts completed was not
      significantly different from their matched controls. However, concussed athletes
      who missed playing time had a significantly higher heart rate during the steady
      state exercise session. During this same period, they also exhibited a greater
      rise in heart rate over time. CONCLUSION: These findings indicate that exercise
      capacity is unaffected in concussed athletes who are asymptomatic at rest.
      However, their heart rate response to submaximal exercise is increased.

PMID- 15562180
TI  - An evaluation of differences in hip external rotation strength and range of
      motion between female dancers and non-dancers.
AB  - OBJECTIVES: To evaluate the differences in hip external rotation (ER) strength
      and inner, outer, and total hip ER range of motion (ROM) between dancers and non
      dancers and between left and right sides in each group. METHODS: Seventy one
      subjects (34 dancers and 37 non-dancers) volunteered for this study. The strength
      (truncated range average torque (TRAT), work, and angle specific torque (AST)) of
      the hip external rotator muscle group, through the full available active hip ER
      ROM, was evaluated using concentric isokinetic (30 degrees /s) testing on a
      KinCom dynamometer. Adjustment for lean body mass (LBM) was made for comparison
      of strength between groups. A two way repeated analysis of covariance was used to
      compare strength between groups. A two way repeated analysis of variance was used
      to compare strength between sides and ROM between groups and sides. Bonferroni
      correction was made for multiple analyses, and significance was accepted at
      p<or=0.05. RESULTS: AST at 0 degrees , 20 degrees , 30 degrees , and 40 degrees
      of hip ER was greater in the dancers than the non-dancers (p<or=0.022). TRAT,
      work, AST(0 degrees ), AST(20 degrees ), and AST(30 degrees ) of hip ER were all
      greater on the right side than the left (p = 0.007) in both groups. Dancers had
      greater inner ER ROM (p = 0.013) and less outer ER ROM than non-dancers
      (p<or=0.001). There was no difference in total ER ROM between groups (p = 0.133).
      The right side had greater inner ER (p<or=0.001) and total ER ROM (p<or=0.001)
      than the left in both groups. CONCLUSIONS: Ballet dancers have greater inner
      range, angle specific strength and inner range ER ROM, demonstrated by a shift in
      the dancers' strength curves. This shift in the strength curve towards the inner
      range of hip ER may be an adaptive training response.

PMID- 15562181
TI  - A simple multistage field test for the prediction of anaerobic capacity in female
      games players.
AB  - OBJECTIVE: To establish the validity of a 15 m multistage shuttle run test (MSRT)
      as a predictor of anaerobic capacity (expressed as mean power output (MPO) from
      the 30 second Wingate anaerobic test (WAnT)) in female university standard games
      players. METHODS: Data came from three phases using a total of 72 players (mean
      (SD) age 20.3 (1.5) years, body mass 64.9 (8.8) kg, and stature 1.67 (0.04) m).
      The repeatability of the MSRT was assessed in phase 1 by applying 95% limits of
      agreement (LoA) to the test and retest results from a random sample of 20
      players. In phase 2, linear relations between MPO and performance on the MSRT
      were investigated in a random sample of 36 players. As a result, a calibration
      model (Y = a + bX) was developed and cross validated in phase 3, in which the
      remaining 36 players performed both the WAnT and the MSRT. Time (seconds) to
      volitional exhaustion/disqualification from the MSRT was substituted into the
      calibration model from which MPO was predicted. The agreement between MPO
      predicted and MPO measured from the WAnT was quantified using LoA. RESULTS:
      Insignificant bias between repeat applications of the MSRT (mean(diff) (SD(diff))
      = 1.0 (3.5) seconds (4 (14) m), t = 1.23, p = 0.230) was found from phase 1. Data
      were homoscedastic (r = 0.061, p = 0.799) with LoA +/- 6.9 seconds (+/- 27 m). In
      phase 2 the strongest correlation was between MPO (W/kg(0.67)) and time to
      volitional exhaustion/disqualification on the MSRT; r = 0.715 (r(2) = 51.1%, p =
      0.0005). As a result, the calibration model developed was: MPO (W/kg(0.67)) =
      12.5 + (0.2 x time (seconds)) with a standard error of prediction of 2.1
      W/kg(0.67). The cross validation in phase 3 showed insignificant bias between
      measured and predicted MPO (mean(diff) (SD(diff)) = 0.3 (2.8) W/kg(0.67), t =
      0.75, p = 0.460). Data were homoscedastic (r = 0.05, p = 0.774) with LoA +/- 5.5
      W/kg(0.67). CONCLUSIONS: The MSRT requires minimal equipment and training of
      assessors, and it is easy to perform. In the population studied, it provides
      scores that are repeatable, and anaerobic capacity (MPO) can be successfully
      predicted from its performance. It would seem therefore to be a useful field
      based test for use by female games players, their coaches, and support
      scientists.

PMID- 15562182
TI  - Sodium ingestion and the prevention of hyponatraemia during exercise.

PMID- 15562184
TI  - Including walnuts in a low-fat/modified-fat diet improves HDL cholesterol-to
      total cholesterol ratios in patients with type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to examine the effect of a moderate-fat diet
      inclusive of walnuts on blood lipid profiles in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: This was a parallel randomized controlled trial
      comparing three dietary advice groups each with 30% energy as fat: low fat,
      modified low fat, and modified low fat inclusive of 30 g of walnuts per day.
      Fifty-eight men and women, mean age 59.3 +/- 8.1 years, started the trial.
      Dietary advice was given at baseline with monthly follow-up and fortnightly phone
      calls for support. Body weight, percent body fat, blood lipids, HbA1c, total
      antioxidant capacity, and erythrocyte fatty acid levels were measured at 0, 3,
      and 6 months. Data were assessed by repeated-measures ANOVA with an intention-to
      treat model. RESULTS: The walnut group achieved a significantly greater increase
      in HDL cholesterol-to-total cholesterol ratio (P=0.049) and HDL (P=0.046) than
      the two other treatment groups. A 10% reduction in LDL cholesterol was also
      achieved in the walnut group, reflecting a significant effect by group (P=0.032)
      and time (P=0.036). There were no significant differences between groups for
      changes in body weight, percent body fat, total antioxidant capacity, or HbA1c
      levels. The higher dietary polyunsaturated fat-to-saturated fat ratio and intakes
      of omega-3 fatty acids in the walnut group were confirmed by erythrocyte
      biomarkers of dietary intake. CONCLUSIONS: Structured "whole of diet" advice that
      included 30 g of walnuts/day delivering substantial amounts of polyunsaturated
      fatty acid improved the lipid profile of patients with type 2 diabetes.

PMID- 15562183
TI  - Evidence for complex system integration and dynamic neural regulation of skeletal
      muscle recruitment during exercise in humans.
AB  - A model is proposed in which the development of physical exhaustion is a relative
      rather than an absolute event and the sensation of fatigue is the sensory
      representation of the underlying neural integrative processes. Furthermore,
      activity is controlled as part of a pacing strategy involving active neural
      calculations in a "governor" region of the brain, which integrates internal
      sensory signals and information from the environment to produce a
      homoeostatically acceptable exercise intensity. The end point of the exercise
      bout is the controlling variable. This is an example of a complex, non-linear,
      dynamic system in which physiological systems interact to regulate activity
      before, during, and after the exercise bout.

PMID- 15562185
TI  - Diet, growth, and the risk for type 1 diabetes in childhood: a matched case
      referent study.
AB  - OBJECTIVE: To study the association between type 1 diabetes risk and previous
      intake of energy, accounting for body size and previous intake of nutrients and
      foods, accounting for the energy intake. RESEARCH DESIGN AND METHODS: We
      conducted an incident population-based case-referent study in Stockholm, Sweden,
      including 99 of 100 eligible 7- to 14-year-old diabetic children and 180 of 200
      age-, sex-, and area-matched referent children identified through the Swedish
      population register. Average daily energy and nutrient intake 1 year before
      diabetes diagnosis/interview was estimated using the food frequency questionnaire
      with assessment of consumed food amounts. Mean SD scores of growth measurements
      taken during the last 4 years before the diagnosis were used. Odds ratios (ORs)
      were calculated by conditional logistic regression. RESULTS: Average intake of
      energy, carbohydrate, fat, and protein was significantly higher among the case
      subjects as well as mean weight-for-age SD score. Higher energy intake and weight
      for-age were both associated with increased diabetes risk after adjustment for
      each other: OR (95% CI) for medium and high levels of energy intake were 1.33
      (0.52-3.42) and 5.23 (1.67-16.38), respectively, and for weight-for-age were 3.20
      (1.30-7.88) and 3.09 (1.16-8.22), respectively. High intake of carbohydrates,
      especially disaccharides and sucrose, increased diabetes risk. CONCLUSIONS:
      Higher energy intake and larger body size were independently associated with
      increased diabetes risk. Of the different nutrients, higher intake of
      carbohydrates, particularly disaccharides and sucrose, increased the risk.
      Lifestyle habits leading to higher energy intake and more rapid growth in
      childhood may contribute to the increase of childhood-onset type 1 diabetes by
      different mechanisms.

PMID- 15562186
TI  - Diabetes incidence in 0- to 14-year age-group in Italy: a 10-year prospective
      study.
AB  - OBJECTIVE: The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group
      was established to coordinate the registries of type 1 diabetes in Italy. This
      report is based on 3,606 children younger than 15 years diagnosed with type 1
      diabetes and prospectively registered during 1990-1999 by nine centers, covering
      >35% of the Italian population. RESEARCH DESIGN AND METHODS: Registries were
      pooled in four geographic macro-areas: north, central, south, and insular. The
      completeness of registration was assessed by the capture-recapture method.
      Poisson regression analysis was used to evaluate temporal trend in incidence.
      RESULTS: Large variations in incidence were confirmed not only between Sardegna
      and the mainland but also among peninsular areas. In Sardegna, there was an
      excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence
      showed average increases of 3.6% (P <0.001) and 3.7% (P <0.001) per year in
      peninsular Italy and in Sardegna, respectively. Significant increases in
      incidence rates were found in boys aged 10-14 years (6.7%, 95% CI 0.5-13.3) and
      in girls aged 5-9 years (6.6%, 0.5-13.1) living in the southern area. The
      incidence rate also increased in boys aged 10-14 years (5.0%, 0.3-10) and in
      girls aged 0-4 years (4.9%, 0.8-9.1) living in Sardegna. CONCLUSIONS: Italy is a
      country with large geographical variations in incidence rates of type 1 diabetes.
      However, the rates are evenly increasing both in the mainland and Sardegna,
      suggesting that similar environmental factors are operating over populations that
      have different genetic backgrounds.

PMID- 15562187
TI  - Diagnosis of type 2 diabetes at an older age: effect on mortality in men and
      women.
AB  - OBJECTIVE: To compare the mortality of people who were diagnosed with type 2
      diabetes over 65 years of age with that of nondiabetic individuals. RESEARCH
      DESIGN AND METHODS: Using a population-based diabetes information system for an
      observational cohort study in Tayside, Scotland, people who were diagnosed with
      type 2 diabetes over the age of 65 years between 1993 and 2002 were identified.
      Nondiabetic comparators, matched for age and sex, were identified from the
      nondiabetic population. The two cohorts were followed up for mortality and
      cardiovascular mortality according to death certification records. RESULTS: There
      were 3,594 people with type 2 diabetes (48% male) and 7,188 matched comparators
      identified in the study. Over a mean follow-up period of 4.6 +/- 2.9 years for
      3,594 people with type 2 diabetes and 7,188 comparators, 909 (25.3%) patients in
      the diabetic cohort and 1,651 (23.0%) in the nondiabetic cohort died. The
      adjusted relative risk for mortality in the diabetic cohort compared with the
      nondiabetic cohort was 1.06 (95% CI 0.94-1.19) for men and 1.29 (1.15-1.45) for
      women. Cardiovascular deaths accounted for 49.4% of the deaths in people with and
      45.2% in those without diabetes (adjusted relative risk 1.01 [0.93-1.10]).
      CONCLUSIONS: Men diagnosed with type 2 diabetes over the age of 65 years have no
      excess mortality compared with their nondiabetic counterparts, a finding that was
      not replicated for women.

PMID- 15562188
TI  - Clinical outcomes and adherence to medications measured by claims data in
      patients with diabetes.
AB  - OBJECTIVE: Although poor medication adherence may contribute to inadequate
      diabetes control, ways to feasibly measure adherence in routine clinical practice
      have yet to be established. The present study was conducted to determine whether
      pharmacy claims-based measures of medication adherence are associated with
      clinical outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS: The
      study setting was a large, integrated delivery and financial system serving the
      residents of southeastern Michigan. The study population consisted of 677
      randomly selected patients aged > or =18 years with a diagnosis of diabetes,
      hypercholesterolemia, and hypertension and who filled at least one prescription
      for either an antidiabetic, lipid-lowering, or antihypertensive drug in each of
      the 3 study years (1999-2001). The main outcome measures were HbA1c, LDL
      cholesterol levels, and blood pressure. RESULTS: Nonadherent patients had both
      statistically and clinically worse outcomes than adherent patients. Even after
      adjusting for demographic and clinical characteristics, nonadherence was
      significantly associated with HbA1c and LDL cholesterol levels. A 10% increase in
      nonadherence to metformin and statins was associated with an increase of 0.14% in
      HbA1c and an increase of 4.9 mg/dl in LDL cholesterol levels. Nonadherence to ACE
      inhibitors was not significantly associated with blood pressure. CONCLUSIONS:
      Claims-based measures of medication adherence are associated with clinical
      outcomes in patients with diabetes and may therefore prove to be useful in
      clinical practice. More research is needed on methods to introduce claims-based
      adherence measurements into routine clinical practice and how to use these
      measurements to effectively improve adherence and health outcomes in chronic care
      management.

PMID- 15562189
TI  - Trends in the prevalence and ratio of diagnosed to undiagnosed diabetes according
      to obesity levels in the U.S.
AB  - OBJECTIVE: To examine trends in the prevalence of diagnosed and undiagnosed
      diabetes and the proportion of total cases previously diagnosed, according to
      obesity status in the U.S. over the past 40 years. RESEARCH DESIGN AND METHODS:
      We assembled data from five consecutive cross-sectional national surveys:
      National Health Examination Survey I (1960-1962), National Health and Nutrition
      Examination Survey (NHANES) I (1971-1974), NHANES II (1976-1980), NHANES III
      (1988-1994), and NHANES 1999-2000. Diagnosed diabetes was ascertained, and height
      and weight were measured in adults aged 20-74 years in all surveys. In NHANES II,
      NHANES III, and NHANES 1999-2000, a fasting glucose level > or =126 mg/dl was
      used to identify cases among individuals not reporting diabetes. Design-based
      analyses and Bayesian models estimate the probability that prevalence of diabetes
      increased within four BMI groups (<25, 25-29, 30-34, and > or =35 kg/m2).
      RESULTS: In the U.S. population aged 20-74 years between 1976-1980 and 1999-2000,
      significant increases in the prevalence of diagnosed diabetes (3.3-5.8%,
      probability >99.9%) were accompanied by nonsignificant increases in undiagnosed
      diabetes (2.0-2.4%, 66.6%). This resulted in an increase in total diabetes (5.3
      8.2%, >99.9%) and a modest nonsignificant increase in the proportion of cases
      that were diagnosed (62-70%, 62.4%). However, these trends varied considerably by
      BMI level. In individuals with BMI > or =35 kg/m2, diagnosed diabetes increased
      markedly (from 4.9% in 1960, to 8.6% during 1976-1980, to 15.1% in 1999-2000;
      probability >99.9%), whereas undiagnosed diabetes declined considerably (12.5%
      during 1976-1980 to 3.2% in 1999-2000, probability of increase 4.5%) Therefore,
      the proportion of total diabetes cases that were diagnosed increased from 41 to
      83% (probability 99.9%) among individuals with BMI > or =35 kg/m2. By comparison,
      changes in prevalence within BMI strata <35 kg/m2 were modest and there was no
      increase in the percent of total cases that were diagnosed. CONCLUSIONS: National
      surveys over the last several decades have found large increases in diagnosed
      diabetes, particularly in overweight and obese individuals, but this has been
      accompanied by large decreases in undiagnosed diabetes only among individuals
      with BMI > or =35 kg/m2. This suggests that improvements in diabetes awareness
      and detection are most prominent among this subgroup.

PMID- 15562190
TI  - Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health
      and Nutrition Examination Survey.
AB  - OBJECTIVE: To determine the association between serum 25-hydroxyvitamin D (25OHD)
      and diabetes risk and whether it varies by ethnicity. RESEARCH DESIGN AND
      METHODS: We performed an analysis of data from participants who attended the
      morning examination of the Third National Health and Nutrition Examination Survey
      (1988-1994), a cross-sectional survey of a nationally representative sample of
      the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were
      available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic
      blacks, and 1,726 Mexican Americans) aged > or =20 years with fasting and/or 2-h
      plasma glucose and serum insulin measurements. RESULTS: Adjusting for sex, age,
      BMI, leisure activity, and quarter of year, ethnicity-specific odds ratios (ORs)
      for diabetes (fasting glucose > or =7.0 mmol/l) varied inversely across quartiles
      of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11-0.60] for non-Hispanic
      whites and 0.17 [0.08-0.37] for Mexican Americans) in the highest vitamin D
      quartile (25OHD > or =81.0 nmol/l) compared with the lowest 25OHD (< or =43.9
      nmol/l). This inverse association was not observed in non-Hispanic blacks.
      Homeostasis model assessment of insulin resistance (log e) was inversely
      associated with serum 25OHD in Mexican Americans (P=0.0024) and non-Hispanic
      whites (P=0.058) but not non-Hispanic blacks (P=0.93), adjusting for confounders.
      CONCLUSIONS: These results show an inverse association between vitamin D status
      and diabetes, possibly involving insulin resistance, in non-Hispanic whites and
      Mexican Americans. The lack of an inverse association in non-Hispanic blacks may
      reflect decreased sensitivity to vitamin D and/or related hormones such as the
      parathyroid hormone.

PMID- 15562191
TI  - Outcomes in type 1 diabetic pregnancies: a nationwide, population-based study.
AB  - OBJECTIVE: The aim of this study was to compare pregnancy outcomes in type 1
      diabetic pregnancies with the background population. RESEARCH DESIGN AND METHODS:
      This nationwide prospective multicenter study took place in eight Danish centers
      treating pregnant women with type 1 diabetes during 1993-1999. A total of 990
      women with 1,218 pregnancies and delivery after 24 weeks (n=1,215) or early
      termination due to severe congenital malformations (n=3) were included. Data were
      collected prospectively by one to three caregivers in each center and reported to
      a central registry. RESULTS: The perinatal mortality rate was 3.1% in type 1
      diabetic pregnancies compared with 0.75% in the background population (RR 4.1
      [95% CI 2.9-5.6]), and the stillbirth rate was 2.1% compared with 0.45 (4.7 [3.2
      7.0]). The congenital malformation rate was 5.0% in the study population and 2.8%
      (1.7 [1.3-2.2]) in the background population. Six of the perinatal deaths (16%)
      were related to congenital malformations. Only 34% of women performed daily home
      monitoring of blood glucose at conception, and 58% received preconceptional
      guidance. Pregnancies with serious adverse outcomes (perinatal death and/or
      congenital malformations) were characterized by higher HbA1c values before and
      during pregnancy and a lesser degree of maternal self-care and preconceptional
      guidance. Women who performed daily self-monitoring of blood glucose at any time
      during pregnancy had lower HbA1c values than women who did not measure their
      daily profile. Likewise, daily self-monitoring was associated with a reduction in
      serious adverse outcomes. The caesarean section rate was 55.9 and 12.6%,
      respectively, and the risk of preterm delivery was 41.7 and 6.0%, respectively.
      CONCLUSIONS: Type 1 diabetic pregnancies are still complicated by considerably
      higher rates of severe perinatal complications compared with the background
      population, and women with poor self-care are at the highest risk. Adequate
      glycemic control using daily glucose monitoring before and during pregnancy is a
      crucial step toward reaching the goals of the St. Vincent declaration.

PMID- 15562192
TI  - Factors associated with preterm delivery in women with type 1 diabetes: a cohort
      study.
AB  - OBJECTIVE: The reported rate of preterm delivery in women with type 1 diabetes
      ranges from 22 to 45%, but the reasons are unclear. The purpose of this study was
      to identify factors associated with preterm delivery in these women. RESEARCH
      DESIGN AND METHODS: We studied the influence of maternal and diabetes-related
      factors on the occurrence of preterm delivery in 168 single pregnancies occurring
      in 127 women with type 1 diabetes. Women with spontaneous or indicated preterm
      delivery were compared with those who delivered after 37 weeks of gestation using
      polytomous logistic regression. RESULTS: The overall rate of preterm delivery was
      24%, fivefold higher than the French prematurity rate in single pregnancy.
      Preterm delivery was spontaneous in 9% and indicated in 15%. HbA1c > or =7% at
      delivery was associated with spontaneous preterm delivery (odds ratio [OR] 5.3
      [95% CI 1.1-26.8]). Nulliparity (12.0 [2.3-64.1]), progression of nephropathy
      (7.7 [1.3-46.9]), preeclampsia (12.0 [3.1-47.1]), and HbA1c > or =7% (7.5 [1.5
      37.9]) at delivery were all associated with indicated preterm delivery. Preterm
      delivery was associated with significant neonatal morbidity as the risks for
      neonatal hypoglycemia and respiratory distress syndrome were increased by three-
      to sixfold compared with the reference group. CONCLUSIONS: The rate of preterm
      delivery remains high in women with type 1 diabetes. Different factors were
      associated with spontaneous and indicated preterm delivery, respectively. Because
      poor glycemic control was a risk factor for both outcomes, part of preterm
      delivery might be preventable.

PMID- 15562193
TI  - End-stage renal disease-associated managed care costs among patients with and
      without diabetes.
AB  - OBJECTIVE: To examine the direct costs of care before and after onset of end
      stage renal disease (ESRD) for patients with and without diabetes based on
      analyses of retrospective healthcare claims data. RESEARCH DESIGN AND METHODS:
      Patients with onset of ESRD between January 1998 though June 2002 were identified
      based on use of dialysis, renal transplantation, or other ESRD-related services.
      Continuous health plan enrollment > or =12 months before and > or =1 month after
      ESRD onset was required. The costs calculated include both observed and adjusted
      estimates; the latter were calculated using generalized linear models,
      controlling for demographic and clinical characteristics, "onset" period, and
      duration of follow-up. Analyses focus on the diabetic ESRD patient and include a
      comparison with ESRD patients without diabetes. RESULTS: The study included 2,020
      patients with diabetes and 2,170 without diabetes; 63% of patients were >50 years
      of age. Average costs were relatively stable before ESRD ($1,535 to $4,357 for
      diabetes, $1,082 to $2,447 for no diabetes) but more than doubled in the month
      preceding onset ($9,152 and $8,211, respectively). Postonset, average monthly per
      patient costs escalated sharply in the 1st month ($26,507 and $26,789), declined
      steadily through month 6, and remained flat but elevated thereafter. Adjusted
      annual costs per patient pre- and postonset of ESRD were significantly higher for
      diabetes (P <0.0001); annual costs were 69% ($38,041 vs. $22,538) and 79%
      ($96,014 vs. $53,653) higher pre- and postonset, respectively. CONCLUSIONS: The
      economic burden of ESRD in the year after onset is substantial, particularly
      among patients with diabetes.

PMID- 15562194
TI  - Blood glucose and risk of cardiovascular disease in the Asia Pacific region.
AB  - OBJECTIVE: To assess the shape and strength of the association between usual
      blood glucose and cardiovascular disease (CVD) in Asian and Australasian cohorts
      and to determine the impact of adjusting for other determinants of CVD risk and
      excluding people with diabetes. RESEARCH DESIGN AND METHODS: Relative risk
      estimates and 95% CIs were calculated from Cox models, stratified by sex and
      cohort, and adjusted for age at risk on individual participant data from 17
      cohort studies. Repeat measurements of blood glucose were used to adjust for
      regression dilution bias. RESULTS: Fasting blood glucose data were available for
      237,468 participants, and during approximately 1.2 million person-years of follow
      up, there were 1,661 stroke and 816 ischemic heart disease (IHD) events. Data
      were also available on 27,996 participants with nonfasting glucose measurements.
      Continuous positive associations were demonstrated between usual fasting glucose
      and the risks of CVD down to at least 4.9 mmol/l. Overall, each 1 mmol/l lower
      usual fasting glucose was associated with a 21% (95% CI 18-24%) lower risk of
      total stroke and a 23% (19-27%) lower risk of total IHD. The associations were
      similar in men and women, across age-groups, and in Asian compared with
      Australasian (Australia and New Zealand) populations. Adjusting for potential
      confounders or removing those with diabetes as baseline did not substantially
      affect the associations. Associations for nonfasting glucose were weaker than
      those with fasting glucose. CONCLUSIONS: Fasting blood glucose is an important
      determinant of CVD burden, with considerable potential benefit of usual blood
      glucose lowering down to levels of at least 4.9 mmol/l.

PMID- 15562195
TI  - Peripheral arterial disease, diabetes, and mortality.
AB  - OBJECTIVE: The aims of this study were to provide estimates of 1) the risk of
      mortality for individuals with both diabetes and peripheral arterial disease
      (PAD) relative to that for individuals with either condition alone and 2) the
      association between PAD progression and mortality for individuals with diabetes,
      PAD, and both conditions. RESEARCH DESIGN AND METHODS: This longitudinal cohort
      study was conducted in Rochester, Minnesota. Local residents age 50-70 years with
      a prior diagnosis of PAD and/or diabetes were identified from the Mayo Clinic
      diagnostic registry and invited to a baseline examination (1977-1978). Those who
      met inclusion criteria were assessed for PAD progression at 2 and 4 years and
      followed for vital status through 31 December 1999. RESULTS: The numbers who met
      criteria for PAD, diabetes, and both conditions at baseline were 149, 238, and
      186, respectively. Within each group, observed survival was less than expected (P
      <0.001). The adjusted risk of death for both conditions was 2.2 times that for
      PAD alone. Among the 449 who returned at 4 years, the risk of subsequent death
      was greater for those whose PAD had progressed; among individuals with diabetes
      alone at baseline, 100% (17 of 17) who met criteria for PAD progression were dead
      by 31 December 1999 compared with 62% (111 of 178) of those who had not met
      criteria (adjusted relative hazard 2.29 [95% CI 1.30-4.02], P=0.004). The
      increased mortality associated with PAD progression was significant only for
      individuals with diabetes (alone or with PAD). CONCLUSIONS: Diabetes is a risk
      factor for both PAD and PAD-associated mortality, emphasizing the critical need
      to detect and monitor PAD in diabetic patients.

PMID- 15562196
TI  - Family and disease management in African-American patients with type 2 diabetes.
AB  - OBJECTIVE: The aim of this project is to specify features of family life that are
      associated with disease management in African Americans with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: A total of 159 African-American patients with type 2
      diabetes were assessed on three domains of family life (structure/organization,
      world view, and emotion management) and three key dimensions of disease
      management (morale, management behaviors, and glucose regulation). Analyses
      assessed the associations of family factors with disease management. RESULTS:
      Multivariate tests for the main effects of three family variables were
      significantly related to the block of disease management variables for morale
      (F=3.82; df=12,363; P <0.0001) and behavior (2.12; 9,329; P <0.03). Structural
      togetherness in families was positively related to diabetes quality of life
      (DQOL)-Satisfaction (P <0.01). High family coherence, a world view that life is
      meaningful and manageable, was positively associated with general health (P
      <0.05) and DQOL-Impact (P <0.05) and negatively associated with depressive
      symptoms (P <0.001). Emotion management, marked by unresolved family conflict
      about diabetes, was related to more depressive symptoms (P <0.001), lower DQOL
      Satisfaction (P <0.01), and lower DQOL-Impact (P <0.001). No family measures were
      related to HbA1c levels. CONCLUSIONS: The family domain of emotion management
      demonstrates the strongest associations with diabetes management in African
      American patients, followed by family beliefs. Patient morale is the aspect of
      disease management that seems most related to family context.

PMID- 15562197
TI  - Depressive symptoms, insulin resistance, and risk of diabetes in women at
      midlife.
AB  - OBJECTIVE: To examine depression and 3-year change in insulin resistance and risk
      of diabetes and whether associations vary by race. RESEARCH DESIGN AND METHODS:
      We analyzed data from 2,662 Caucasian, African-American, Hispanic, Japanese
      American, and Chinese-American women without a history of diabetes from the Study
      of Women's Health Across the Nation. We estimated regression coefficients and
      odds ratios to determine whether depression (Center for Epidemiological Studies
      Depression Scale score > or =16) predicted increases in homeostasis model
      assessment of insulin resistance (HOMA-IR) and greater risk of incident diabetes,
      respectively, over 3 years. RESULTS: Mean baseline HOMA-IR was 1.31 (SD 0.86) and
      increased 0.05 units per year for all women (P <0.0001). A total of 97 incident
      cases of diabetes occurred. Depression was associated with absolute levels of
      HOMA-IR (P <0.04) but was unrelated to changes in HOMA-IR; associations did not
      vary by race. The association between depression and HOMA-IR was eliminated after
      adjustment for central adiposity (P=0.85). Depression predicted a 1.66-fold
      greater risk of diabetes (P <0.03), which became nonsignificant after adjustment
      for central adiposity (P=0.12). We also observed a depression-by-race interaction
      (P <0.05) in analyses limited to Caucasians and African Americans, the only
      groups with enough diabetes cases to reliably test this interaction. Race
      stratified models showed that depression predicted 2.56-fold greater risk of
      diabetes in African Americans only, after risk factor adjustment (P=0.008).
      CONCLUSIONS: Depression is associated with higher HOMA-IR values and incident
      diabetes in middle-aged women. These associations are mediated largely through
      central adiposity. However, African-American women with depression experience
      increased risk of diabetes independent of central adiposity and other risk
      factors.

PMID- 15562198
TI  - The impact of the Micro-Lightguide O2C for the quantification of tissue ischemia
      in diabetic foot ulcers.
AB  - OBJECTIVE: Tissue oxygen supply is crucial for wound healing. Especially in
      diabetic foot lesions, the chances for healing are mainly dependent on the
      presence or absence of ischemia. This study investigates the impact of the tissue
      O2 analysis system "O2C" for noninvasive quantification of tissue oxygenation in
      diabetic foot ulcer patients. RESEARCH DESIGN AND METHODS: O2C assessed relative
      blood flow (flow), flow velocity (velo), and hemoglobin concentration (rHb) and
      hemoglobin oxygenation (SO2) at 2 and 6 mm depth (means +/- SE). 1) Measurements
      were performed on intact skin of the forefoot and forearm of 20 healthy
      volunteers on 2 consecutive days. 2) Parameters were assessed on intact skin of
      the forefoot of diabetic foot ulcer patients (n=14). 3) Measurements were
      performed directly at the wound site in diabetic patients (n = 14). RESULTS: 1)
      Flow, velo, rHb, and SO2 at 2 and 6 mm depth were not significantly different
      when measured at 2 consecutive days. 2) There were no significant differences
      between diabetic subjects and healthy volunteers. Only flow in 6 mm depth was
      significantly higher in diabetic subjects (75 +/- 13 vs. 51 +/- 0.4 arbitrary
      units [AU], P <0.05). When diabetic foot ulcer patients were split into healers
      and nonhealers, initial readings of SO2 at 2 mm (32 +/- 6 vs. 44 +/- 3%, P <0.05)
      and flow in 6 mm (28 +/- 1 vs. 51 +/- 0.6 AU, P <0.05) were significantly reduced
      in nonhealers compared with control subjects, whereas in healers flow in 6 mm (70
      +/- 0.6 vs. 51 +/- 0.6 AU, P <0.05) was significantly higher than that in control
      subjects. 3) Initial SO2, rHb, flow, and velo were significantly lower in
      nonhealing compared with healing wounds. CONCLUSIONS: O2C is a new reliable and
      valid method for noninvasive measurement of tissue oxygenation and microvascular
      blood flow in patients with diabetic foot ulcers.

PMID- 15562199
TI  - Dose-response effect of a single administration of oral hexyl-insulin
      monoconjugate 2 in healthy nondiabetic subjects.
AB  - OBJECTIVE: 1) To evaluate the effect of a single oral dose of hexyl-insulin
      monoconjugate 2 (HIM2) on the rate of whole-body glucose disposal (Rd) and
      endogenous glucose production (EGP) in healthy nondiabetic subjects, 2) to
      examine the reproducibility of HIM2 on glucose metabolism, and 3) to compare the
      results obtained with HIM2 with those using a bioequivalent dose of subcutaneous
      lispro insulin. RESEARCH DESIGN AND METHODS: Six healthy subjects ([means +/- SE]
      aged 31 +/- 5 years and BMI 23.1 +/- 3.9 kg/m2) participated in four studies
      performed in random order on separate days. Subjects ingested a single dose of
      HIM2 (0.125, 0.5, and 0.75 mg/kg) or received subcutaneous lispro insulin (0.1
      units/kg). Studies were performed with [3-3H]glucose, and plasma glucose
      concentration was maintained at basal levels for 4 h with the euglycemic clamp
      technique. After 6 weeks, subjects participated in two repeat studies to examine
      the reproducibility of HIM2 (0.5 mg/kg) and lispro insulin (0.1 units/kg).
      RESULTS: Fasting plasma insulin (7 muU/ml) increased to a maximum of 102, 321,
      and 561 muU/ml at 60 min after all three HIM2 doses (0.125, 0.5, and 0.75 mg/kg,
      respectively). A dose-related decrease in basal EGP was observed as the HIM2
      dosage was increased from 0 to 0.125 to 0.5 mg/kg (P <0.05 vs. each preceding
      dose). Suppression of EGP was similar with the 0.5- and 0.75-mg/kg HIM2 doses. A
      dose-related stimulation of basal Rd was observed as the HIM2 dosage was
      increased from 0 to 0.125 to 0.5 (P <0.05 vs. each preceding dose) to 0.75 mg/kg
      (P <0.10 vs. preceding dose). Rd (0-240 min) was increased by 0.5 mg/kg oral HIM2
      to a value similar to 0.1 units/kg lispro insulin. The 0.125-mg/kg HIM2 dose
      reduced EGP (0-240 min) to a value that was similar to 0.1 units/kg lispro
      insulin. The variability in the effect of HIM2 and lispro on Rd (25 +/- 7 vs. 27
      +/- 1%, respectively) and on suppression of EGP (19 +/- 1 vs. 19 +/- 0.7%,
      respectively) was similar. CONCLUSIONS: Oral HIM2 suppresses EGP and increases
      tissue Rd in a dose-dependent manner. The effects of HIM2 on EGP and Rd persisted
      at 240 min, even though plasma insulin concentration had returned to basal
      levels. Oral HIM2 may provide an effective and reproducible means of controlling
      postprandial plasma glucose excursions in diabetic patients.

PMID- 15562200
TI  - Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in
      metformin-treated patients with type 2 diabetes.
AB  - OBJECTIVE: To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV
      inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing
      metformin treatment. RESEARCH DESIGN AND METHODS: We conducted a 12-week,
      randomized, double-blind, placebo-controlled trial in 107 patients with type 2
      diabetes with a 40-week extension in those completing the core study and
      agreeing, together with the investigator, to extend treatment to 1 year. Placebo
      (n=51) or LAF237 (50 mg once daily, n=56) was added to ongoing metformin
      treatment (1,500-3,000 mg/day). HbA1c and fasting plasma glucose (FPG) were
      measured periodically, and standardized meal tests were performed at baseline,
      week 12, and week 52. RESULTS: In patients randomized to LAF237, baseline HbA1c
      averaged 7.7 +/- 0.1% and decreased at week 12 (Delta=-0.6 +/- 0.1%), whereas
      HbA1c did not change from a baseline of 7.9 +/- 0.1% in patients given placebo
      (between-group difference in DeltaHbA1c=-0.7 +/- 0.1%, P <0.0001). Mean prandial
      glucose and FPG were significantly reduced in patients receiving LAF237 versus
      placebo by 2.2 +/- 0.4 mmol/l (P <0.0001) and 1.2 +/- 0.4 mmol/l (P=0.0057),
      respectively, but plasma insulin levels were not affected. At end point of the
      extension, the between-group differences in change in mean prandial glucose,
      insulin, and FPG were -2.4 +/- 0.6 mmol/l (P=0.0001), 40 +/- 16 pmol/l
      (P=0.0153), and -1.1 +/- 0.5 mmol/l (P=0.0312), respectively. HbA1c did not
      change from week 12 to week 52 in LAF237-treated patients (n=42) but increased in
      participants given placebo (n=29). The between-group difference in DeltaHbA1c
      after 1 year was -1.1 +/- 0.2% (P <0.0001). CONCLUSIONS: Data from this study
      demonstrate that LAF237 effectively prevents deterioration of glycemic control
      when added to metformin monotherapy in type 2 diabetes.

PMID- 15562201
TI  - Continuous glucose monitoring and the reality of metabolic control in preschool
      children with type 1 diabetes.
AB  - OBJECTIVE: To determine using the MiniMed continuous glucose monitoring system
      (CGMS) 1) whether twice-daily insulin injection therapy achieves adequate control
      in preschool children with type 1 diabetes and 2) whether the CGMS is more
      informative than self-monitoring of blood glucose (SMBG) regarding glucose
      control and well tolerated by preschool children and their families. RESEARCH
      DESIGN AND METHODS: Ten children <6 years of age with type 1 diabetes were
      monitored twice using the CGMS. The distribution of glucose values was analyzed,
      particularly the frequency, duration, and distribution of hypoglycemia. We
      analyzed the accuracy of the CGMS in detecting hypoglycemia as well as the
      clinical relevance of the difference between CGMS and SMBG values. RESULTS:
      Although hypoglycemia was more frequent during the night (0.8 nighttime episodes
      . subject(-1) . 24 h(-1) vs. 0.3 daytime episodes . subject(-1) . 24 h(-1)), the
      difference did not reach statistical significance (P=0.07). However, nighttime
      episodes lasted longer than daytime episodes (1.2 vs. 0.2 h . subject(-1) . 24 h(
      1), P=0.006). Hypoglycemia accounted for 7% and normoglycemia for 24%, while
      hyperglycemia occurred 64% of the time, with postprandial hyperglycemia being an
      almost universal feature (94 +/- 7% of all postmeal values). The CGMS correlated
      well with SMBG without significant clinical discrepancy. The CGMS sensitivity to
      detect hypoglycemia was 70% with a specificity of 99%; however, the CGMS detected
      twice as many total episodes as SMBG (82 vs. 40). CONCLUSIONS: Twice-daily
      insulin injection rarely achieves control in preschool children with type 1
      diabetes. The CGMS is well tolerated by patients and has the advantage of
      revealing daily glucose trends missed by SMBG.

PMID- 15562202
TI  - Two-year statin therapy does not alter the progression of intima-media thickness
      in patients with type 2 diabetes without manifest cardiovascular disease.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the most important cause of mortality
      in patients with type 2 diabetes. We aimed to determine the effect of statin
      therapy versus placebo on the progression of carotid intima-media thickness (IMT)
      in type 2 diabetic patients without manifest CVD. RESEARCH DESIGN AND METHODS: A
      randomized, placebo-controlled, double-blind clinical trial was performed in 250
      patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or
      placebo daily. In August 2001, when cerivastatin was withdrawn from the market,
      0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the
      study. The primary end point was the change of mean common carotid IMT, as
      measured by B-mode ultrasound, over 2 years. RESULTS: Common carotid IMT at
      baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and
      did not change significantly after 2 years. There was no significant difference
      in IMT change in any carotid segment between the groups. LDL cholesterol was
      reduced by 25% in the statin group and increased by 8% in the placebo group (P
      <0.001). Cardiovascular events occurred in 12 patients in the placebo group and
      two patients in the statin group (P=0.006). CONCLUSIONS: There was no effect of 2
      years' statin therapy on carotid IMT in type 2 diabetic subjects. The natural
      history of IMT in our patients was milder than anticipated. In contrast, we
      observed a significantly lower cardiovascular event rate on statin therapy.
      Prognostic tools other than IMT should be explored in this patient group.

PMID- 15562203
TI  - Association between urinary albumin excretion and serum dehydroepiandrosterone
      sulfate concentration in male patients with type 2 diabetes: a possible link
      between urinary albumin excretion and cardiovascular disease.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of mortality and
      morbidity in patients with type 2 diabetes. Both elevated urinary albumin
      excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are
      associated with increased CVD mortality. This raises the possibility of DHEA as a
      causal intermediate linking urinary albumin excretion to CVD. RESEARCH DESIGN AND
      METHODS: Relationships of urinary albumin excretion to serum DHEA sulfate (DHEA
      S) concentration and to major cardiovascular risk factors, including blood
      pressure, serum lipid concentration, glycemic control (HbA1c), and BMI, were
      investigated in 357 consecutive men with type 2 diabetes. RESULTS: Serum DHEA-S
      concentrations were lower in patients with macroalbuminuria (866.5 +/- 523.8
      ng/ml, P <0.0001) and in those with microalbuminuria (1,014.4 +/- 525.3 ng/ml,
      P=0.0006) than in patients with normoalbuminuria (1,232.6 +/- 542.4 ng/ml). Serum
      DHEA-S concentration correlated inversely with log (urinary albumin excretion)
      (r=-0.227, P <0.0001). Multiple regression analysis demonstrated that duration of
      diabetes (beta=0.147, P=0.0075), HbA1c (beta=0.156, P=0.0048), BMI (beta=0.194,
      P=0.0007), systolic blood pressure (beta=0.195, P=0.0005), and serum DHEA-S
      concentration (beta=-0.192, P=0.0010) were independent determinants of log
      (urinary albumin excretion). CONCLUSIONS: Serum DHEA-S concentration, which
      correlated inversely with degree of urinary albumin excretion, may contribute to
      the link between elevated urinary albumin excretion and higher CVD mortality in
      male patients with type 2 diabetes.

PMID- 15562204
TI  - Gender difference in the impact of type 2 diabetes on coronary heart disease
      risk.
AB  - OBJECTIVE: To explain the stronger effect of type 2 diabetes on the risk of
      coronary heart disease (CHD) in women compared with men. RESEARCH DESIGN AND
      METHODS: The study population consisted of 1,296 nondiabetic subjects and 835
      type 2 diabetic subjects aged 45-64 years without cardiovascular disease. The end
      points were CHD death and a major CHD event (CHD death or nonfatal myocardial
      infarction). The follow-up time was 13 years. RESULTS: Major CHD event rate per
      1,000 person-years was 11.6 in nondiabetic men, 1.8 in nondiabetic women, 36.3 in
      diabetic men, and 31.6 in diabetic women. The diabetes-related hazard ratio for a
      major CHD event from the Cox model, adjusted for age and area of residence, was
      2.9 (95% CI 2.2-3.9) in men and 14.4 (8.4-24.5) in women, and after further
      adjustment for cardiovascular risk factors, 2.8 (2.0-3.7) and 9.5 (5.5-16.9),
      respectively. The burden of conventional risk factors in the presence of diabetes
      was greater in women than in men at baseline. Prospectively, elevated blood
      pressure, low HDL cholesterol, and high triglycerides contributed to diabetes
      related CHD risk more in women than in men. However, after adjusting for
      conventional risk factors, a substantial proportion of diabetes-related CHD risk
      remained unexplained in both genders. CONCLUSIONS: The stronger effect of type 2
      diabetes on the risk of CHD in women compared with men was in part explained by a
      heavier risk factor burden and a greater effect of blood pressure and atherogenic
      dyslipidemia in diabetic women.

PMID- 15562205
TI  - Noninvasive angiography and assessment of left ventricular function using
      multislice computed tomography in patients with type 2 diabetes.
AB  - OBJECTIVE: Early identification of coronary artery disease (CAD) in patients with
      diabetes is important because these patients are at increased risk for CAD and
      have worse outcome than nondiabetic patients after CAD is diagnosed. Recently,
      noninvasive coronary angiography and assessment of left ventricular function has
      been demonstrated with multislice computed tomography (MSCT). The purpose of the
      present study was to validate this approach in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: MSCT was performed in 30 patients with confirmed
      type 2 diabetes. From the MSCT images, coronary artery stenoses (> or =50%
      luminal narrowing) and left ventricular function (left ventricular ejection
      fraction, regional wall motion) were evaluated and compared with results of
      conventional angiography and two-dimensional echocardiography. RESULTS: Two
      hundred twenty of 256 coronary artery segments (86%) were interpretable with
      MSCT. In these segments, sensitivity and specificity for detection of coronary
      artery stenoses were 95%. Including the uninterpretable segments, sensitivity and
      specificity were 81 and 82%, respectively. Bland-Altman analysis in the
      comparison of left ventricular ejection fractions demonstrated a mean difference
      of -0.48 +/- 3.8% for MSCT and echocardiography, which was not significantly
      different from 0. Agreement between the two modalities for assessment of regional
      contractile function was excellent (91%, kappa statistic 0.81). CONCLUSIONS:
      Accurate noninvasive evaluation of both the coronary arteries and left
      ventricular function with MSCT is feasible in patients with type 2 diabetes. This
      noninvasive approach may allow optimal identification of high-risk patients.

PMID- 15562206
TI  - Radial artery tonometry demonstrates arterial stiffness in children with type 1
      diabetes.
AB  - OBJECTIVE: To determine if children with type 1 diabetes have increased arterial
      stiffness by estimating augmentation index with the simple noninvasive technique
      of radial artery tonometry. RESEARCH DESIGN AND METHODS: We studied 98 type 1
      diabetic children and 57 healthy control subjects, ages 10-18 years, matched for
      age, sex, race, and BMI, generating 43 matched pairs. Radial artery tonometry was
      performed, and blood was collected for analysis of fasting lipids, HbA1c,
      glucose, and cytokines in all children. RESULTS: Children with diabetes had a
      significantly higher augmentation index corrected to a heart rate of 75 (AI75)
      than their matched control subjects. Mean AI75 in type 1 diabetic subjects was
      1.11 +/- 10.15 versus -3.32 +/- 10.36 in control subjects. The case-control
      difference was 5.20 +/- 11.02 (P=0.0031). CONCLUSIONS: Children with type 1
      diabetes have increased arterial stiffness compared with healthy control
      subjects. Radial artery tonometry is a simple noninvasive technique that could be
      added to the armamentarium of tests used to provide cardiovascular risk
      stratification in children with type 1 diabetes.

PMID- 15562207
TI  - Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in
      diabetes: implications for cardiovascular risk and effects of multifactorial
      intervention.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and
      Ang-2 are mediators of angiogenesis. More recent data suggest that the balance
      between these growth factors may affect vascular endothelial integrity. Because
      diabetes is closely associated with endothelial perturbation, we studied plasma
      levels of these angiogenic growth factors in patients with diabetes; their
      relationship with glycemia, inflammation, and endothelial damage/dysfunction; and
      the effect of intensified cardiovascular risk management. RESEARCH DESIGN AND
      METHODS: We measured plasma VEGF, Ang-1, and Ang-2 alongside plasma von
      Willebrand factor (vWf) and urine albumin-to-creatinine ratio (marking
      endothelial damage/dysfunction) and interleukin (IL)-6 in 94 patients (38 with
      overt cardiovascular disease [CVD]) with diabetes and 34 normal control subjects.
      RESULTS: Plasma vWf (P=0.009), IL-6 (P <0.001), VEGF (P=0.001), and Ang-2
      (P=0.001), but not Ang-1 (P=0.635), were higher in diabetic patients with and
      without CVD than in control subjects. On multivariate analysis, HbA1c was an
      independent predictor of plasma VEGF (P=0.032) and Ang-2 (P=0.015). Of the 94
      patients, a subgroup of 33 patients with and 31 patients without CVD participated
      in a year of intensified cardiovascular risk management. HbA1c and LDL
      cholesterol reduced significantly with treatment, along with associated
      reductions in plasma vWf and VEGF in both groups (P <0.001). Ang-2 decreased (P
      <0.001) only in patients without CVD. There were no significant changes in plasma
      IL-6 levels in both groups. CONCLUSIONS: Plasma Ang-2 (but not Ang-1), like VEGF
      levels, are selectively elevated in patients with diabetes and are associated
      with indexes of endothelial damage/dysfunction, regardless of vascular disease.
      Intensive multifactorial intervention is associated with reductions in plasma
      VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an
      improved vascular profile with treatment.

PMID- 15562208
TI  - Decreased plasma lipoprotein lipase in hypoadiponectinemia: an association
      independent of systemic inflammation and insulin resistance.
AB  - OBJECTIVE: Adiponectin is a plasma protein expressed in adipose tissue.
      Hypoadiponectinemia is associated with low HDL cholesterol and high plasma
      triglycerides, which also characterize lipoprotein lipase (LPL) deficiency
      syndromes. Recently, dramatically increased LPL activity was reported in mice
      overexpressing adiponectin. We therefore speculated that adiponectin may directly
      affect LPL in humans. RESEARCH DESIGN AND METHODS: We measured plasma adiponectin
      and postheparin LPL in 206 nondiabetic men and in a second group of 110 patients
      with type 2 diabetes. Parameters were correlated with markers of systemic
      inflammation (C-reactive protein [CRP]) and insulin resistance (homeostatis model
      assessment of insulin resistance [HOMA-IR]). RESULTS: Nondiabetic subjects with
      decreased plasma adiponectin had lower LPL activity (r=0.42, P <0.0001). This
      association of plasma adiponectin with LPL activity was confirmed in the second
      group of patients with type 2 diabetes (r=0.37, P <0.0001). Multivariate analysis
      revealed that adiponectin was the strongest factor influencing LPL activity,
      accounting for 23% of the variation in LPL activity in nondiabetic subjects and
      for 26% of the variation in LPL activity in type 2 diabetic patients. These
      associations were independent of plasma CRP and HOMA-IR. CONCLUSIONS: These
      results demonstrate an association of decreased postheparin LPL activity with low
      plasma adiponectin that is independent of systemic inflammation and insulin
      resistance. Therefore, LPL may represent a link between low adiponectin levels
      and dyslipidemia in both nondiabetic individuals and patients with type 2
      diabetes.

PMID- 15562209
TI  - The LDIflare: a novel test of C-fiber function demonstrates early neuropathy in
      type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to evaluate a novel method for assessing the
      axon reflex and to determine its value in detecting neuropathy in type 2
      diabetes. RESEARCH DESIGN AND METHODS: The neurogenic flare response to
      nociceptive stimuli is mediated by an axon reflex involving small unmyelinated C
      fibers. We developed a method to assess this reflex involving skin heating to 44
      degrees C to evoke the flare followed by scanning the site using a laser Doppler
      imager (LDI) to measure the area; we termed this method LDIflare. To confirm its
      neurogenic nature, we examined the LDIflare in eight healthy subjects before and
      after topical administration of anesthesia. We used this technique to detect C
      fiber neuropathy in people with type 2 diabetes. A total of 36 subjects were
      studied: 12 subjects with neuropathy (group DN), 12 subjects without neuropathy
      (group DC), and 12 age- and sex-matched control subjects (group NC). For
      comparison, small-fiber function was also assessed using the Computer Aided
      Sensory Evaluator-IV (CASE IV) (WR Medical Electronics, Stillwater, MN). RESULTS:
      In the eight healthy control subjects, LDIflare was markedly reduced after
      topical administration of anesthesia (1.62 [1.45-1.72] vs. 5.2 cm2 [3.9-5.9], P
      <0.0001), confirming its neurogenic nature. Similarly, in neuropathic subjects,
      LDIflare was significantly smaller compared with normal and diabetic control
      subjects (LDIflare area: DN 1.3 cm2 [0.9-1.8], NC 5.5 cm2 [3.9-5.8], and DC 2.8
      cm2 [2.5-3.8]; P <0.0001 and P=0.01, respectively). The group without neuropathy
      (DC) also demonstrated a reduced flare compared with the NC group (P=0.01). In
      contrast, C-fiber function assessed by evaluating the quantitative thermal
      thresholds (CASE IV) did not detect a difference between the latter two groups.
      CONCLUSIONS: This study confirms the neurogenic nature of the LDIflare and
      clearly demonstrates loss of C-fiber function in neuropathic subjects with type 2
      diabetes. Moreover, it demonstrates C-fiber dysfunction before its detection by
      other currently available methods, including CASE IV. The LDIflare seems to be a
      simple objective method to detect early neuropathy and may be of value in
      assessing therapeutic interventions aimed at preventing or reversing C-fiber
      dysfunction.

PMID- 15562210
TI  - Sympathetic and parasympathetic neuropathy are frequent in both type 1 and type 2
      diabetic patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the frequency of sympathetic
      versus parasympathetic neuropathy among type 1 and type 2 diabetic patients.
      RESEARCH DESIGN AND METHODS: There were 43 patients with type 1 and 17 with type
      2 diabetes who were investigated. Sympathetic nerve function was assessed by
      measurement of the vasoconstriction (VAC) index by laser Doppler perfusion
      imaging of a locally heated finger followed by indirect cooling. Parasympathetic
      nerve function was assessed by R-R interval variation during deep breathing as
      measured by the expiration/inspiration (E/I) ratio. Results were expressed as age
      corrected z scores in SD; VAC index >1.64 SD and E/I ratio <-1.64 SD were
      considered abnormal. RESULTS: VAC index was abnormal in 40% with type 1 and 41%
      with type 2 diabetes, whereas the E/I ratio was abnormal in 42% with type 1 and
      65% with type 2 diabetes. There was a clear association between VAC index and E/I
      ratio among type 1 (rs=0.525; P=0.0002) but not among type 2 (rs=0.10) diabetic
      patients. Among type 2 diabetic patients, the degree of dysfunction was most
      severe regarding parasympathetic function (P=0.0167). CONCLUSIONS: Sympathetic
      and parasympathetic neuropathy were frequent in both type 1 and type 2 diabetic
      patients. However, there was a difference between the two types of diabetes.
      Sympathetic and parasympathetic nerve functions correlated in type 1 but not in
      type 2 diabetic patients. The explanation for this discrepancy might be that
      parasympathetic nerve function was most severely affected among type 2 diabetic
      patients.

PMID- 15562211
TI  - Autonomic symptoms and diabetic neuropathy: a population-based study.
AB  - OBJECTIVE: The prevalence of autonomic symptoms and deficits in certain systems
      is known, but a comprehensive autonomic symptom profile in diabetes is not
      available. We aimed to estimate this using a laboratory evaluation of autonomic
      function and a validated self-report measure of autonomic symptoms in patients
      and matched control subjects from the population-based Rochester Diabetic
      Neuropathy Study. RESEARCH DESIGN AND METHODS: Participants included 231 patients
      with diabetes (type 1, n=83; type 2, n=148) and 245 healthy age-matched control
      subjects. We assessed symptoms using a validated self-report instrument
      (Autonomic Symptom Profile) and evaluated the severity and distribution of
      autonomic deficits (cardiovagal, sudomotor, adrenergic) with the objective,
      laboratory-based Composite Autonomic Severity Score (CASS). RESULTS: Autonomic
      symptoms were present more commonly in type 1 than in type 2 diabetes, with
      symptoms of orthostatic intolerance, secretomotor, urinary control, diarrhea, and
      sleep disturbance and pupillomotor, vasomotor, and erectile dysfunction
      significantly increased over healthy control subjects in type 2 diabetic
      patients. The prevalence of autonomic impairment was 54% in type 1 and 73% in
      type 2 diabetic patients. Severity of autonomic failure was mild overall (mean
      CASS 2.3; maximum 10), with orthostatic hypotension occurring in 8.4 and 7.4% of
      type 1 and 2 diabetic patients, respectively. Fourteen percent of patients had a
      CASS > or =5, indicating moderate to severe generalized autonomic failure. The
      correlation of symptoms with autonomic deficits (CASS) was better in type 1 than
      type 2 diabetic subjects and was weak overall. CONCLUSIONS: These findings
      indicate that autonomic symptoms and deficits are common in diabetes, but mild in
      severity, and that the correlation between symptom scores and deficits is overall
      weak in mild diabetic neuropathy, emphasizing the need to separately evaluate
      autonomic symptoms.

PMID- 15562212
TI  - Visceral and central abdominal fat and anthropometry in relation to diabetes in
      Asian Indians.
AB  - OBJECTIVE: The objective of the study was to examine body fat distribution using
      computed tomography (CT), dual-energy X-ray absorptiometry (DEXA), and
      anthropometry in relation to type 2 diabetes in urban Asian Indians. RESEARCH
      DESIGN AND METHODS: This is a case-control study of 82 type 2 diabetic and 82 age
      and sex-matched nondiabetic subjects from the Chennai Urban Rural Epidemiology
      Study, an ongoing epidemiological study in southern India. Visceral,
      subcutaneous, and total abdominal fat were measured using CT, while DEXA was used
      to measure central abdominal and total body fat. Anthropometric measures included
      BMI, waist circumference, sagittal abdominal diameter (SAD), and waist-to-hip
      ratio. RESULTS: Visceral and central abdominal fat showed a strong correlation
      with each other (P <0.0001), and kappa analysis revealed a fairly good agreement
      between tertiles of visceral and central abdominal fat (kappa=0.44, P <0.0001).
      Diabetic subjects had significantly higher visceral (P=0.005) and central
      abdominal (P=0.011) fat compared with nondiabetic subjects. Waist circumference
      and SAD showed a strong correlation with visceral (P <0.01) and central abdominal
      (P <0.0001) fat in both diabetic and nondiabetic subjects. Logistic regression
      analysis revealed visceral (odds ratio [OR] 1.011, P=0.004) and central abdominal
      (OR 1.001, P=0.013) fat to be associated with diabetes, even after adjusting for
      age and sex. CONCLUSIONS: Visceral and central abdominal fat showed a strong
      association with type 2 diabetes. Both measures correlated well with each other
      and with waist circumference and SAD in diabetic and nondiabetic urban Asian
      Indians.

PMID- 15562213
TI  - Alcohol consumption and the prevalence of the Metabolic Syndrome in the US.: a
      cross-sectional analysis of data from the Third National Health and Nutrition
      Examination Survey.
AB  - OBJECTIVE: The aim of this study was to examine the relations of alcohol
      consumption to the prevalence of the metabolic syndrome and its components in the
      U.S. population. RESEARCH DESIGN AND METHODS: We performed a cross-sectional
      analysis on data from 8,125 participants from the Third National Health and
      Nutrition Examination Survey who were evaluated for each component of the
      metabolic syndrome, using the National Cholesterol Education Program criteria,
      fasting insulin, and alcohol consumption. Current alcohol consumption was defined
      as > or =1 alcoholic drink per month. RESULTS: After adjustment for age, sex,
      race/ethnicity, education, income, tobacco use, physical activity, and diet,
      subjects who consumed 1-19 and > or =20 drinks of alcohol per month had odds
      ratios (ORs) for the prevalence of the metabolic syndrome of 0.65 and 0.34,
      respectively (P <0.05 for all), compared with current nondrinkers. These findings
      were particularly noteworthy for beer and wine drinkers. The association of > or
      =20 alcoholic drinks per month with the prevalence of the metabolic syndrome was
      consistent across ethnicities but was most striking in white men and women (ORs
      0.35 and 0.22, respectively; P <0.05). Alcohol consumption was significantly and
      inversely associated with the prevalence of the following three components of the
      metabolic syndrome: low serum HDL cholesterol, elevated serum triglycerides, high
      waist circumference, as well as hyperinsulinemia (P <0.05 for all). CONCLUSIONS:
      Mild to moderate alcohol consumption is associated with a lower prevalence of the
      metabolic syndrome, with a favorable influence on lipids, waist circumference,
      and fasting insulin. This association was strongest among whites and among beer
      and wine drinkers.

PMID- 15562214
TI  - Association between inflammation and insulin resistance in U.S. nondiabetic
      adults: results from the Third National Health and Nutrition Examination Survey.
AB  - Clinical and epidemiological data indicate that inflammation may be associated
      with insulin resistance. We examined the association between inflammatory
      markers, such as ferritin, uric acid, white cell counts, fibrinogen, and C
      reactive protein, and insulin resistance among 5,959 adults, aged > or =20 years
      and without diabetes (fasting glucose <126 mg/dl and not taking diabetes
      medication), who participated in the Third National Health and Nutrition
      Examination Survey. Insulin resistance was calculated using the homeostasis model
      assessment (HOMA). Levels of ferritin, uric acid, white cell counts, fibrinogen,
      and C-reactive protein were significantly higher in individuals with a higher
      HOMA of insulin resistance (HOMA-IR). After adjustment for age, sex, race,
      education, physical inactivity, current and former smoking, alcohol intake, use
      of nonsteroidal anti-inflammatory drugs, systolic blood pressure, BMI, waist
      circumference, serum total cholesterol, and triglycerides, a 1-SD higher ferritin
      (126.1 ng/ml), uric acid (1.4 mg/dl), white blood cell count (2.2 x 10(9)/l), and
      fibrinogen (80.6 mg/dl) was associated with a 0.10 (95% CI 0.03-0.17, P=0.004),
      0.16 (0.08-0.24, P <0.001), 0.16 (0.09-0.22, P <0.001), and 0.12 (0.05-0.18,
      P=0.001) higher HOMA-IR, respectively. Clinically elevated C-reactive protein (>
      or =1.0 mg/dl) was associated with a 0.63 (0.23-1.04, P=0.003) higher HOMA-IR.
      These findings indicate that elevated levels of inflammatory markers are
      positively and independently associated with insulin resistance. Further studies
      should examine the potential causal effect of inflammation on insulin resistance.

PMID- 15562215
TI  - Prospective association between lung function and the incidence of diabetes:
      findings from the National Health and Nutrition Examination Survey Epidemiologic
      Follow-up Study.
AB  - OBJECTIVE: To determine whether impaired pulmonary function is a significant
      predictor of the incidence of diabetes. RESEARCH DESIGN AND METHODS: Using data
      from the National Health and Nutrition Examination Survey Epidemiologic Follow-Up
      Study, a cohort study of a representative sample of U.S. adults, we examined the
      prospective associations between pulmonary function and incidence of diabetes.
      Our analyses included 4,830 U.S. men and women aged 25-74 years who had a
      baseline interview and examination (including spirometry) from 1971 through 1975
      and were followed through 1992-1993. Incident diabetes (n=443) was based on self-
      or proxy reports, hospitalization, or death certificates. RESULTS: After multiple
      adjustment, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC),
      percentage of predicted FEV1, and percentage of predicted FVC were significantly
      and inversely associated with the incidence of diabetes, but the ratio of FEV1 to
      FVC was not. Obstructive lung disease (defined by the Global Initiative for
      Chronic Obstructive Lung Disease classification) was not significantly associated
      with the incidence of diabetes, but restrictive lung disease was (hazard
      ratio=1.45, 95% CI 1.04-2.03). The association did not differ significantly by
      smoking status. CONCLUSIONS: Although several prospective studies have found that
      impaired pulmonary function may increase the risk for developing diabetes,
      additional research is needed to better understand these relationships and their
      possible implications.

PMID- 15562216
TI  - C-reactive protein levels following acute myocardial infarction: effect of
      insulin infusion and tight glycemic control.

PMID- 15562217
TI  - Sex differences in quality of health care related to ischemic heart disease
      prevention in patients with diabetes: the translating research into action for
      Diabetes (TRIAD) study, 2000-2001.

PMID- 15562218
TI  - World Health Organization-defined metabolic syndrome is a better predictor of
      coronary calcium than the adult treatment panel III criteria in American men aged
      40-49 years.

PMID- 15562219
TI  - Association of health literacy with self-management behavior in patients with
      diabetes.

PMID- 15562220
TI  - Improving quality of care in diabetes through a comprehensive pharmacist-based
      disease management program.

PMID- 15562221
TI  - Prevalence of known diabetes and antidiabetic therapy between 1984/1985 and
      1999/2001 in southern Germany.

PMID- 15562222
TI  - Effects of 8 weeks of flexibility and resistance training in older adults with
      type 2 diabetes.

PMID- 15562223
TI  - Effects of coffee consumption on fasting blood glucose and insulin
      concentrations: randomized controlled trials in healthy volunteers.

PMID- 15562224
TI  - A prospective study of fruit and vegetable intake and the risk of type 2 diabetes
      in women.

PMID- 15562225
TI  - Obesity is associated with larger arterial diameters in Caucasian and African
      American young adults.

PMID- 15562226
TI  - Overweight and components of the metabolic syndrome in college students.

PMID- 15562227
TI  - Prevalence of the metabolic syndrome among adult New Zealanders of Polynesian and
      European descent.

PMID- 15562228
TI  - 2004 presidential address: the sheep, the ostrich, the ant, diabetes, and the
      tragedy of the common.

PMID- 15562229
TI  - Dyslipidemia and the metabolic syndrome.

PMID- 15562230
TI  - Insulin, glycemic control, and C-reactive protein during myocardial infarction.

PMID- 15562231
TI  - Syzygium cumini (L.) Skeels in the treatment of type 2 diabetes: results of a
      randomized, double-blind, double-dummy, controlled trial.

PMID- 15562232
TI  - Primary prevention of type 2 diabetes through nutritional counseling.

PMID- 15562233
TI  - ADHD: a diabetic hyperglycemic dilemma.

PMID- 15562234
TI  - Pioglitazone treatment of insulin resistance in a patient with Werner's syndrome.

PMID- 15562235
TI  - Continuous subcutaneous insulin infusion in older patients with type 1 diabetes.

PMID- 15562236
TI  - A Korean patient with fulminant autoantibody-negative type 1 diabetes.

PMID- 15562237
TI  - Effectiveness of diabetic therapeutic footwear in preventing reulceration:
      response to Maciejewski et al.

PMID- 15562238
TI  - The American Cancer Society, American Diabetes Association, and American Heart
      Association joint statement on preventing cancer, cardiovascular disease, and
      diabetes: where are the social determinants?

PMID- 15562241
TI  - Comparative roles of microvascular and nerve function in foot ulceration in type
      2 diabetes: response to Krishnan et al.

PMID- 15562243
TI  - Real world effectiveness of rosiglitazone added to maximal (tolerated) doses of
      metformin and a sulphonylurea agent: response to Roy et al.

PMID- 15562245
TI  - Variability in activity may precede diabetic foot ulceration: response to
      Armstrong et al.

PMID- 15562246
TI  - Expression and secretion of inflammation-related adipokines by human adipocytes
      differentiated in culture: integrated response to TNF-alpha.
AB  - The expression profile of a series of adipokine genes linked to inflammation has
      been examined by quantitative PCR during the differentiation of human
      preadipocytes to adipocytes in primary culture, together with the integrated
      effects of TNF-alpha on the expression of these adipokines in the differentiated
      adipocytes. Expression of the genes encoding adiponectin, leptin, and haptoglobin
      was highly differentiation dependent, the mRNA being undetectable
      predifferentiation with the level peaking 9-15 days postdifferentiation. Although
      angiotensinogen (AGT) and monocyte chemoattractant protein-1 (MCP-1) were both
      expressed before differentiation, the mRNA level increased markedly on
      differentiation. The expression of nerve growth factor (NGF) and plasminogen
      activator inhibitor-1 (PAI-1) fell after differentiation, whereas that of TNF
      alpha and IL-6 changed little. Measurement of adiponectin, leptin, MCP-1, and NGF
      in the medium by ELISA showed that the protein secretion pattern paralleled
      cellular mRNA levels. Treatment of differentiated human adipocytes with TNF-alpha
      (5 or 100 ng/ml for 24 h) significantly decreased the level of adiponectin, AGT,
      and haptoglobin mRNA (by 2- to 4-fold), whereas that of leptin and PAI-1 was
      unchanged. In contrast, TNF-alpha induced substantial increases in IL-6, TNF
      alpha, metallothionein, MCP-1, and NGF mRNAs, the largest increase being with MCP
      1 (14.5-fold). MCP-1 and NGF secretion increased 8- to 10-fold with TNF-alpha,
      whereas leptin and adiponectin did not change. These results demonstrate that
      there are major quantitative changes in adipokine gene expression during
      differentiation of human adipocytes and that TNF-alpha has a pleiotropic effect
      on inflammation-related adipokine production, the synthesis of MCP-1 and NGF
      being highly induced by the cytokine.

PMID- 15562247
TI  - Adipose tissue gene expression profiling reveals distinct molecular pathways that
      define visceral adiposity in offspring of maternal protein-restricted rats.
AB  - There is increasing evidence that poor early growth confers an increased risk of
      type 2 diabetes, hypertension, and other features of the metabolic syndrome in
      later life. We hypothesized that this may result from poor nutrition during early
      life exerting permanent effects on the structure and function of key metabolic
      organ systems. To study the long-term impact of early-life undernutrition on
      susceptibility to visceral adiposity, we used a rat model of maternal protein
      restriction (MPR) in which dams were fed a low-protein diet (containing 8%
      instead of 20% protein in control diet) throughout pregnancy and lactation. MPR
      offspring were born smaller than controls (offspring of dams on control diet) and
      in adulthood developed visceral adiposity. We compared the pattern of gene
      expression in visceral adipose tissue (VAT) between MPR offspring and controls
      with Affymetrix rat expression arrays. Of the total number of genes and expressed
      sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT.
      We identified 650 transcripts as differentially expressed > or =1.5-fold in the
      VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of
      genes involved in carbohydrate, lipid, and protein metabolism. A number of genes
      involved in adipocyte differentiation, angiogenesis, and extracellular matrix
      remodeling were also upregulated. However, in marked contrast to other rodent
      models of obesity, the expression of a large number of genes associated with
      inflammation was reduced in this rat model. Thus visceral adiposity in this early
      life programmed rat model is marked by dynamic changes in the transcriptional
      profile of VAT. Our data provide new insights into the molecular mechanisms that
      underlie the early-life programming of visceral adiposity.

PMID- 15562248
TI  - Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to
      immune activation and functional capacity.
AB  - Chronic heart failure is characterized by changes in skeletal muscle that
      contribute to physical disability. Most studies to date have investigated defects
      in skeletal muscle oxidative capacity. In contrast, less is known about how heart
      failure affects myofibrillar protein metabolism. Thus we examined the effect of
      heart failure on skeletal muscle myofibrillar protein metabolism, with a specific
      emphasis on changes in myosin heavy chain (MHC) protein content, synthesis, and
      isoform distribution in 10 patients with heart failure (63 +/- 3 yr) and 11
      controls (70 +/- 3 yr). In addition, we examined the relationship of MHC protein
      metabolism to inflammatory markers and physical function. Although MHC and actin
      protein content did not differ between groups, MHC protein content decreased with
      increasing disease severity in heart failure patients (r = -0.748, P < 0.02),
      whereas actin protein content was not related to disease severity. No difference
      in MHC protein synthesis was found between groups, and MHC protein synthesis
      rates were not related to disease severity. There were, however, relationships
      between C-reactive protein and both MHC protein synthesis (r = -0.442, P = 0.05)
      and the ratio of MHC to mixed muscle protein synthesis (r = -0.493, P < 0.03).
      Heart failure patients showed reduced relative amounts of MHC I (P < 0.05) and a
      trend toward increased MHC IIx (P = 0.06). In regression analyses, decreased MHC
      protein content was related to decreased exercise capacity and muscle strength in
      heart failure patients. Our results demonstrate that heart failure affects both
      the quantity and isoform distribution of skeletal muscle MHC protein. The fact
      that MHC protein content was related to both exercise capacity and muscle
      strength further suggests that quantitative alterations in MHC protein may have
      functional significance.

PMID- 15562249
TI  - Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating
      serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle.
AB  - Stearoyl-CoA desaturase (SCD) has recently been shown to be a critical control
      point of lipid partitioning and body weight regulation. Lack of SCD1 function
      significantly increases insulin sensitivity in skeletal muscles and corrects the
      hypometabolic phenotype of leptin-deficient ob/ob mice, indicating the direct
      antilipotoxic action of SCD1 deficiency. The mechanism underlying the metabolic
      effects of SCD1 mutation is currently unknown. Here we show that SCD1 deficiency
      reduced the total ceramide content in oxidative skeletal muscles (soleus and red
      gastrocnemius) by approximately 40%. The mRNA levels and activity of serine
      palmitoyltransferase (SPT), a key enzyme in ceramide synthesis, as well as the
      incorporation of [14C]palmitate into ceramide were decreased by approximately 50%
      in red muscles of SCD1-/- mice. The content of fatty acyl-CoAs, which contribute
      to de novo ceramide synthesis, was also reduced. The activity and mRNA levels of
      carnitine palmitoyltransferase I (CPT I) and the rate of beta-oxidation were
      increased in oxidative muscles of SCD1-/- mice. Furthermore, SCD1 deficiency
      increased phosphorylation of AMP-activated protein kinase (AMPK), suggesting that
      AMPK activation may be partially responsible for the increased fatty acid
      oxidation and decreased ceramide synthesis in red muscles of SCD1-/- mice. SCD1
      deficiency also reduced SPT activity and ceramide content and increased AMPK
      phosphorylation and CPT I activity in muscles of ob/ob mice. Taken together,
      these results indicate that SCD1 deficiency reduces ceramide synthesis by
      decreasing SPT expression and increasing the rate of beta-oxidation in oxidative
      muscles.

PMID- 15562250
TI  - Abdominal adipose tissue cytokine gene expression: relationship to obesity and
      metabolic risk factors.
AB  - Adipose tissue is a major source of inflammatory and thrombotic cytokines. This
      study investigated the relationship of abdominal subcutaneous adipose tissue
      cytokine gene expression to body composition, fat distribution, and metabolic
      risk during obesity. We determined body composition, abdominal fat distribution,
      plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF
      alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/-
      0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15)
      also underwent an OGTT. In all women, visceral fat volume was negatively related
      to leptin (r = -0.46, P < 0.05) and tended to be negatively related to
      adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women,
      fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA
      index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression;
      fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin
      (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression;
      and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin
      area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene
      expression. Also, adiponectin gene expression was significantly lower in women
      with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/-
      0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous
      adipose tissue expression of inflammatory cytokines is a potential mechanism
      linking obesity with its metabolic comorbidities.

PMID- 15562251
TI  - Combined ingestion of protein and free leucine with carbohydrate increases
      postexercise muscle protein synthesis in vivo in male subjects.
AB  - The present study was designed to determine postexercise muscle protein synthesis
      and whole body protein balance following the combined ingestion of carbohydrate
      with or without protein and/or free leucine. Eight male subjects were randomly
      assigned to three trials in which they consumed drinks containing either
      carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein,
      and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed,
      continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples
      and muscle biopsies collected to assess fractional synthetic rate (FSR) in the
      vastus lateralis muscle as well as whole body protein turnover during 6 h of
      postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu
      compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%,
      respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole
      body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials
      compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu
      trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial.
      Protein balance was negative during recovery in the CHO trial but positive in the
      CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein
      balance was significantly greater compared with values observed in the CHO+PRO
      and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of
      postexercise recovery, was significantly greater in the CHO+PRO+Leu trial
      compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h,
      respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial
      (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine
      stimulates muscle protein synthesis and optimizes whole body protein balance
      compared with the intake of carbohydrate only.

PMID- 15562252
TI  - Long-term calorie restriction reduces proton leak and hydrogen peroxide
      production in liver mitochondria.
AB  - Calorie restriction (CR) without malnutrition increases maximal life span in
      diverse species. It has been proposed that reduction in energy expenditure and
      reactive oxygen species (ROS) production could be a mechanism for life span
      extension with CR. As a step toward testing this theory, mitochondrial proton
      leak, H2O2 production, and markers of oxidative stress were measured in liver
      from FBNF1 rats fed control or 40% CR diets for 12 or 18 mo. CR was initiated at
      6 mo of age. Proton leak kinetics curves, generated from simultaneous measures of
      oxygen consumption and membrane potential, indicated a decrease in proton leak
      after 18 mo of CR, while only a trend toward a proton leak decrease was observed
      after 12 mo. Significant shifts in phosphorylation and substrate oxidation curves
      also occurred with CR; however, these changes occurred in concert with the proton
      leak changes. Metabolic control analysis indicated no difference in the overall
      pattern of control of the oxidative phosphorylation system between control and CR
      animals. At 12 mo, no significant differences were observed between groups for
      H2O2 production or markers of oxidative stress. However, at 18 mo, protein
      carbonyl content was lower in CR animals, as was H2O2 production when
      mitochondria were respiring on either succinate alone or pyruvate plus malate in
      the presence of rotenone. These results indicate that long-term CR lowers
      mitochondrial proton leak and H2O2 production, and this is consistent with the
      idea that CR may act by decreasing energy expenditure and ROS production.

PMID- 15562253
TI  - Differing mechanisms of hepatic glucose overproduction in triiodothyronine
      treated rats vs. Zucker diabetic fatty rats by NMR analysis of plasma glucose.
AB  - The metabolic mechanism of hepatic glucose overproduction was investigated in
      3,3'-5-triiodo-l-thyronine (T3)-treated rats and Zucker diabetic fatty (ZDF) rats
      (fa/fa) after a 24-h fast. 2H2O and [U-13C3]propionate were administered
      intraperitoneally, and [3,4-13C2]glucose was administered as a primed infusion
      for 90 min under ketamine-xylazine anesthesia. 13C NMR analysis of monoacetone
      glucose derived from plasma glucose indicated that hepatic glucose production was
      twofold higher in both T3-treated rats and ZDF rats compared with controls, yet
      the sources of glucose overproduction differed significantly in the two models by
      2H NMR analysis. In T3-treated rats, the hepatic glycogen content and hence the
      contribution of glycogenolysis to glucose production was essentially zero; in
      this case, excess glucose production was due to a dramatic increase in
      gluconeogenesis from TCA cycle intermediates. 13C NMR analysis also revealed
      increased phosphoenolpyruvate carboxykinase flux (4x), increased pyruvate cycling
      flux (4x), and increased TCA flux (5x) in T3-treated animals. ZDF rats had
      substantial glycogen stores after a 24-h fast, and consequently nearly 50% of
      plasma glucose originated from glycogenolysis; other fluxes related to the TCA
      cycle were not different from controls. The differing mechanisms of excess
      glucose production in these models were easily distinguished by integrated 2H and
      13C NMR analysis of plasma glucose.

PMID- 15562254
TI  - USP19 is a ubiquitin-specific protease regulated in rat skeletal muscle during
      catabolic states.
AB  - Ubiquitin-dependent proteolysis is activated in skeletal muscle atrophying in
      response to various catabolic stimuli. Previous studies have demonstrated
      activation of ubiquitin conjugation. Because ubiquitination can also be regulated
      by deubiquitinating enzymes, we used degenerate oligonucleotides derived from
      conserved sequences in the ubiquitin-specific protease (UBP) family of
      deubiquitinating enzymes in RT-PCR with skeletal muscle RNA to amplify putative
      deubiquitinating enzymes. We identified USP19, a 150-kDa deubiquitinating enzyme
      that is widely expressed in various tissues including skeletal muscle. Expression
      of USP19 mRNA increased by approximately 30-200% in rat skeletal muscle
      atrophying in response to fasting, streptozotocin-induced diabetes, dexamethasone
      treatment, and cancer. Increased mRNA levels during fasting returned to normal
      with refeeding, but 1 day later than the normalization of rates of proteolysis
      and coincided instead with recovery of muscle mass. Indeed, in all catabolic
      treatments, USP19 mRNA was inversely correlated with muscle mass and provided an
      index of muscle mass that may be useful in many pathological conditions, using
      small human muscle biopsies. The increased expression of this deubiquitinating
      enzyme under conditions of increased proteolysis suggests that it may play a role
      in regeneration of free ubiquitin either coincident with or after proteasome
      mediated degradation of substrates. USP19 may also be involved in
      posttranslational processing of polyubiquitin produced de novo in response to
      induction of the polyubiquitin genes seen under these conditions.
      Deubiquitinating enzymes thus appear involved in muscle wasting and implicate a
      widening web of regulation of genes in the ubiquitin system in this process.

PMID- 15562255
TI  - Reduced PDX-1 expression impairs islet response to insulin resistance and worsens
      glucose homeostasis.
AB  - In type 2 diabetes mellitus, insulin resistance and an inadequate pancreatic beta
      cell response to the demands of insulin resistance lead to impaired insulin
      secretion and hyperglycemia. Pancreatic duodenal homeodomain-1 (PDX-1), a
      transcription factor required for normal pancreatic development, also plays a key
      role in normal insulin secretion by islets. To investigate the role of PDX-1 in
      islet compensation for insulin resistance, we examined glucose disposal, insulin
      secretion, and islet cell mass in mice of four different genotypes: wild-type
      mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired
      insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting
      in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/
      ;PDX-1+/-). The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged
      glucose clearance. GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but
      failed to increase their beta-cell insulin content. These results indicate that
      PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the
      beta-cell's compensatory response to insulin resistance, impairs glucose
      homeostasis, and may contribute to the pathogenesis of type 2 diabetes.

PMID- 15562256
TI  - Differential expression of mu-opioid receptor gene in CXBK and B6 mice by Sp1.
AB  - It is well known that there are individual differences in the sensitivity to
      analgesics. The CXBK mice are characterized by reduced sensitivity to morphine
      and by partial deficiency in mu-opioid receptor (MOR) expression. The sequences
      of MOR genes in CXBK and B6 mice are identical in their coding regions but differ
      at 5'-untranslated region (UTR) nucleotide -202 (C nucleotide in CXBK, but A
      nucleotide in B6). In this report, we identified an Sp1 element (-211 to -204)
      immediately before the polymorphic nucleotide. In electrophoretic mobility shift
      assay, nuclear protein binding to the B6-Sp1 sequence was more efficient than to
      the CXBK-Sp1 sequence, and anti-Sp1 but not anti-CREB antibody interfered with
      the formation of the DNA-protein complex. In MOR-expressing cell lines SH-SY5Y,
      P19, and PC12, B6 MOR promoter possessed high transcription activity than the
      CXBK promoter, and Sp1 inhibitor PDTC reduced the promoter activities. In SL2
      cells that lack endogenous Sp1 expression, B6 and CXBK MOR promoters demonstrated
      equal activity, whereas overexpression of Sp1 in SL2 cells enhanced B6 MOR
      promoter activity better than the CXBK promoter. Together, the A-to-C change at
      MOR 5'-UTR decreases Sp1 binding and MOR gene transcription, which could underlie
      the reduced morphine expression in CXBK mice.

PMID- 15562257
TI  - State-dependent mibefradil block of Na+ channels.
AB  - Mibefradil is a T-type Ca2+ channel antagonist with reported cross-reactivity
      with other classes of ion channels, including K+, Cl-, and Na+ channels. Using
      whole-cell voltage clamp, we examined mibefradil block of four Na+ channel
      isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4
      (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve). Mibefradil
      blocked Nav1.5 in a use/frequency-dependent manner, indicating preferential
      binding to states visited during depolarization. Mibefradil blocked currents of
      all Na+ channel isoforms with similar affinity and a dependence on holding
      potential, and drug off-rate was slowed at depolarized potentials (k(off) was
      0.024/s at -130 mV and 0.007/s at -100 mV for Nav1.5). We further probed the
      interaction of mibefradil with inactivated Nav1.5 channels. Neither the degree
      nor the time course of block was dependent on the stimulus duration, which
      dramatically changed the residency time of channels in the fast-inactivated
      state. In addition, inhibiting the binding of the fast inactivation lid (Nav1.5
      ICM + MTSET) did not alter mibefradil block, confirming that the drug does not
      preferentially interact with the fast-inactivated state. We also tested whether
      mibefradil interacted with slow-inactivated state(s). When selectively applied to
      channels after inducing slow inactivation with a 60-s pulse to -10 mV, mibefradil
      (1 microM) produced 45% fractional block in Nav1.5 and greater block (88%) in an
      isoform (Nav1.4) that slow-inactivates more completely. Our results suggest that
      mibefradil blocks Na+ channels in a state-dependent manner that does not depend
      on fast inactivation but probably involves interaction with one or more slow
      inactivated state(s).

PMID- 15562258
TI  - Abortion surveillance--United States, 2001.
AB  - PROBLEM/CONDITION: CDC began abortion surveillance in 1969 to document the number
      and characteristics of women obtaining legal induced abortions. REPORTING PERIOD
      COVERED: This report summarizes and describes data voluntarily reported to CDC
      regarding legal induced abortions obtained in the United States in 2001.
      DESCRIPTION OF SYSTEM: For each year since 1969, CDC has compiled abortion data
      by state or area of occurrence. During 1973-1997, data were received from or
      estimated for 52 reporting areas in the United States: 50 states, the District of
      Columbia, and New York City. In 1998 and 1999, CDC compiled abortion data from 48
      reporting areas. Alaska, California, New Hampshire, and Oklahoma did not report,
      and data for these states were not estimated. In 2000 and 2001, Oklahoma again
      reported these data, increasing the number of reporting areas to 49. RESULTS: A
      total of 853,485 legal induced abortions were reported to CDC for 2001 from 49
      reporting areas, representing a 0.5% decrease from the 857,475 legal induced
      abortions reported by the same 49 reporting areas for 2000. The abortion ratio,
      defined as the number of abortions per 1,000 live births, was 246 in 2001,
      compared with 245 reported for 2000. This represents a 0.4% increase in the
      abortion ratio. The abortion rate was 16 per 1,000 women aged 15-44 years for
      2001, the same as for 2000. For both the 48 and 49 reporting areas, the abortion
      rate remained relatively constant during 1997-2001. The highest percentages of
      reported abortions were for women who were unmarried (82%), white (55%) and aged
      <25 years (52%). Of all abortions for which gestational age was reported, 59%
      were performed at < or =8 weeks' gestation and 88% at <13 weeks. From 1992 (when
      detailed data regarding early abortions were first collected) through 2001,
      steady increases have occurred in the percentage of abortions performed at < or
      =6 weeks' gestation. A limited number of abortions were obtained at >15 weeks'
      gestation, including 4.3% at 16-20 weeks and 1.4% at > or =21 weeks. A total of
      35 reporting areas submitted data stating that they performed medical
      (nonsurgical) procedures, making up 2.9% of all reported procedures from the 45
      areas with adequate reporting on type of procedure. In 2000 (the most recent year
      for which data are available), 11 women died as a result of complications from
      known legal induced abortion. No deaths were associated with known illegal
      abortion. INTERPRETATION: During 1990-1997, the number of legal induced abortions
      gradually declined. When the same 48 reporting areas are compared, the number of
      abortions decreased during 1996-2001. In 2000 and 2001, even with one additional
      reporting state, the number of abortions declined slightly. In 2000, as in
      previous years, deaths related to legal induced abortions occurred rarely (less
      than one death per 100,000 abortions). PUBLIC HEALTH ACTION: Abortion
      surveillance in the United States continues to provide the data necessary for
      examining trends in numbers and characteristics of women who obtain legal induced
      abortions and to increase understanding of this pregnancy outcome. Policymakers
      and program planners use these data to improve the health and well-being of women
      and infants.

PMID- 15562259
TI  - Detection of ischemia and new insight into left ventricular physiology by strain
      Doppler and tissue velocity imaging: assessment during coronary bypass operation
      of the beating heart.
AB  - BACKGROUND AND OBJECTIVES: Detection of myocardial ischemia in humans by strain
      Doppler and tissue velocity imaging was validated in a novel, experimentally
      designed study model during coronary bypass operation of the beating heart.
      METHODS: Assessment of ischemia was made with an opened chest and pericardium
      inherent in the operative procedure. Longitudinal strain and tissue velocity of
      interventricular septal regions were measured by transesophageal echocardiography
      during occlusion of the left anterior descending coronary artery (LAD). RESULTS:
      Unexpectedly, baseline velocities demonstrated that the apical and basal septum
      moved toward each other during systole. This occurred when the apex was dislodged
      from the pericardial sac to obtain access to the LAD, without any change in
      strain. The preceding motion of all septal regions toward the apex was
      reestablished after the heart was repositioned within the pericardium. In 16
      patients with antegrade LAD flow, strain Doppler detected ischemia during LAD
      occlusion by disclosing systolic lengthening of the apical septum ( P <.01) and
      reduced shortening of the mid septum ( P <.05). The location and degree of
      ischemic changes coincided with the concomitant deterioration of wall motion.
      Tissue velocity changed in the basal and mid septum ( P <.05) but not in the
      apical region, explained by tethering effects and the distinctive motion pattern
      at baseline. There was no evidence of ischemia by invasive hemodynamic measures.
      In 7 patients with retrograde LAD flow, there were no significant changes in
      strain or tissue velocity measurements during LAD occlusion. CONCLUSIONS: Strain
      by Doppler is a sensitive means for detecting myocardial ischemia, also capable
      of correctly localizing the ischemia, as opposed to tissue velocity assessment.
      However, velocity measurements provided new physiological information by
      disclosing the normal longitudinal motion of the heart to be dependent on the
      pericardial sac enveloping the apex, irrespective of the structural integrity of
      the pericardium.

PMID- 15562260
TI  - Assessment of regional myocardial strain by a novel automated tracking system
      from digital image files.
AB  - Myocardial strain imaging by Doppler tissue echocardiography is a useful method
      to quantify regional left ventricular function. However, this method has a
      problem of its Doppler angle dependency. We attempted to quantify myocardial
      strain by a newly developed automated tracking system from digital image files.
      In 6 anesthetized open-chest dogs, a pair of ultrasonic crystals was implanted at
      the inner site and outer site of the left ventricular wall to measure myocardial
      radial strain. B-mode echocardiographic images and trajectories of crystals were
      recorded simultaneously. Three conditions were examined by intravenous infusion
      of dobutamine. We used a pattern matching algorithm, which allowed us to track
      objects from one frame to the next. In 18 image sequences obtained in the 6 dogs,
      there was an excellent correlation in maximal myocardial strain between the two
      methods ( r = 0.92, P < .0001). Thus, this system is a promising tool to provide
      automated quantification of regional myocardial strain.

PMID- 15562261
TI  - Both systolic and diastolic dysfunction characterize nonischemic inhibition of
      myocardial energy metabolism: an experimental strain rate echocardiographic
      study.
AB  - BACKGROUND: Ischemia is primarily a metabolic event. However, regional functional
      changes can be affected by structural alterations. We developed an experimental
      model of sole myocardial energy metabolism inhibition and characterized the
      resulting regional dysfunction. METHODS: In 12 pigs, we regionally inhibited
      creatine kinase (CK) and, consequently, myocyte high-energy phosphate transfer by
      intracoronary administration of iodoacetamide. Myocardial biopsies for CK
      activity and structural analyses and strain rate (SR) echocardiography scans were
      obtained at baseline and 60 minutes after iodoacetamide administration. Plasma
      levels of the CK isoenzyme MB and troponin I were assessed to determine possible
      myocardial damage. RESULTS: CK activity in the iodoacetamide-perfused myocardium
      decreased to 0.5% of the original value and was accompanied by a reduction in
      peak systolic SR ( P < .0001), end-systolic strain ( P < .0001), and peak SRs of
      myocardial early and late filling waves ( P < .0001). Microscopy showed
      contracture without sarcomere disruption. Plasma levels of CK isoenzyme MB and
      troponin I did not change. CONCLUSIONS: Regional inhibition of myocyte energetics
      leads to both systolic and diastolic dysfunction by SR echocardiography, but the
      presence of a residual phosphotransfer protects microstructural integrity.

PMID- 15562262
TI  - Myocardial systolic synchrony measured by Doppler tissue imaging as a role of
      predictor of left ventricular ejection fraction improvement in severe congestive
      heart failure.
AB  - BACKGROUND: The recovery of left ventricular ejection fraction (LVEF) appears to
      be prognostic of survival in congestive heart failure (CHF). The aim of our study
      was to evaluate which parameters appear to predict LVEF improvement in CHF.
      METHODS: In all, 85 patients (age 64 +/- 12 years) with CHF and LVEF <35% were
      enrolled. Doppler tissue imaging was performed on 5 basal and 5 midsegments to
      assess the time from R wave to peak systolic velocity (Ts). The standard
      deviation (SD) of Ts was an indicator of systolics synchrony. After at least 3
      months of intensive medical therapy with beta-blocker and angiotensin-converting
      enzyme inhibitors, follow-up echocardiography was performed. By the change in
      LVEF, we divided patients into group I (<5%, n = 47) and group II (>/=5%, n =
      38). RESULTS: Baseline clinical and echocardiographic parameters were similar in
      both groups. There was negative correlation between SD of Ts and change of LVEF (
      r = -0.43, P < .001). The multivariate analysis shows that SD of Ts and dose of
      beta-blocker were independent predictors of LVEF improvement. CONCLUSION:
      Myocardial systolic synchrony measured by Doppler tissue imaging is a predictor
      for LVEF improvement in severe CHF independently from QRS duration, cause of CHF,
      baseline LVEF, and chamber dimension.

PMID- 15562263
TI  - A new Doppler tissue ratio to revisit systole: the pre-ejectional isovolumic to
      ejectional velocity ratio-application to aging.
AB  - Most diagnostic applications of Doppler tissue echocardiography rely on peak (Pk)
      velocity (V) values of single variables or myocardial V gradient. Whereas age
      related changes in diastolic V are well-known, previous Doppler tissue
      echocardiography studies of systolic function showed no age effect for pre
      ejectional (Ej) isovolumic (PEI) and Ej inward wall motion Pk V. In addition to
      myocardial V gradient, ratios were calculated between PEI and Ej Pk V, and mean V
      averaged over systole (PEI/Ej V ratios) at each layer of the posterior wall using
      M-mode color on two control groups: A (27 +/- 5 years) and B (54 +/- 10 years).
      The only changes were for PEI/Ej V ratios (mean V endocardial 21 +/- 7% vs 34 +/-
      20%, P = .01; mean V epicardial 27 +/- 8% vs 40 +/- 18%, P = .006; Pk epicardial
      V 21 +/- 10% vs 30 +/- 16%, P = .04 for groups A and B, respectively).
      Correlation versus age were r = 0.52 and P = .005 (mean V endocardial), r = 0.50
      and P = .007 (mean V epicardial), and r = 0.32 and P = .03 (Pk epicardial V).
      PEI/Ej V ratios and mean V studied in separate layers showed that the new
      systolic approach had advantages over single variable or Pk V to study age
      related changes.

PMID- 15562264
TI  - Measurement of the Tei index: a comparison of M-mode and pulse Doppler methods.
AB  - BACKGROUND: The Tei index is a useful echocardiographic measure of ventricular
      function in adults and children. Most studies have used pulse or tissue Doppler
      imaging to calculate this index. M-mode, with its higher frame rate and sharp
      deflections, may be an accurate method of calculating the Tei index. METHODS: M
      mode and pulse Doppler (PD) measurement of the Tei index were performed in 68
      children. The mitral closure to opening time ("a") and ejection time ("b")
      intervals for calculating the Tei index were measured by M-mode and PD methods.
      RESULTS: Both M-mode and PD were found to be reproducible methods of calculating
      the Tei index. There was a close correlation between measurements of the "a" and
      "b" intervals by M-mode and PD, with less variability with M-mode than with PD.
      CONCLUSION: M-mode is a simple, reproducible echocardiographic alternative method
      for calculating the Tei index in children and has a lower variance than PD.

PMID- 15562265
TI  - Assessment of propagation velocity by contrast echocardiography for
      standardization of color Doppler propagation velocity measurements.
AB  - BACKGROUND: Color Doppler propagation velocity (Vp) (color-Vp) has not yet been
      standardized, although it should be able to specifically reflect the
      intraventricular movements of left ventricular (LV) inflow. Because contrast
      echocardiography can depict a specified flow, we used this modality to
      standardize measurements of color-Vp of LV inflow. METHODS: We performed contrast
      echocardiographic examinations in 100 patients (70 men, 30 women; age 53 +/- 12
      years). Four types of color-Vp were measured: by the flow wave front method and
      by aliasing method using 3 aliasing velocity levels based on the peak velocity of
      early diastolic flow of transmitral flow. We also determined contrast
      echocardiographic Vp by M-mode imaging of LV inflow (contrast-Vp). RESULTS:
      Contrast-Vp and all 4 types of color-Vp could be compared in 86 patients.
      Contrast-Vp was significantly lower than color-Vp ( P < .01), except for color-Vp
      measured at the aliasing level 50% > peak velocity of early diastolic flow >/=
      40% (color-Vp 40). A close relationship was observed between contrast-Vp and
      color-Vp 40 ( r = 0.801, P < .0001). Contrast-Vp and color-Vp 40 showed high
      ability to detect abnormal transmitral flow patterns according to receiver
      operating characteristics curves (area under curve for contrast-Vp, 0.94; for
      color-Vp 40, 0.90). CONCLUSIONS: Our results should be useful in standardization
      of color-Vp measurement to specifically reflect propagation of the fluid elements
      derived from LV inflow, with ability to distinguish LV filling abnormalities.

PMID- 15562266
TI  - Adenosine triphosphate stress myocardial contrast echocardiography detects
      coronary artery stenosis with greater sensitivity than wall-motion abnormality
      measurements.
AB  - BACKGROUND: Although stress myocardial contrast echocardiography (MCE) can be
      used to detect coronary stenosis, its efficacy relative to other methods, such as
      detection of wall-motion abnormalities, remains unknown. Thus, the goal of this
      study was to compare the sensitivity of MCE versus wall-motion abnormality
      detection in the assessment of coronary artery stenosis. METHOD: Nine dogs with
      severe but nonflow limiting stenosis in the circumflex coronary artery underwent
      evaluation with real-time MCE along the short-axis view during infusion of
      Optison. The equation of y = a (1 - e -betat ) + c, which fits the replenishment
      curve of MCE, was calculated in the midseptum (normal region) and in the lateral
      wall (ischemic region) before and during adenosine triphosphate infusion. Wall
      motion abnormalities were also evaluated by visual assessment and by measurement
      of wall thickening. RESULTS: Area under the receiver operating characteristic
      curve in beta- and A x beta-value, and percent wall thickening, was 0.963, 0.963,
      and 0.889, respectively, indicating that the diagnostic accuracy for detecting
      the coronary artery stenosis by real-time MCE was higher than that by the wall
      motion assessment. CONCLUSION: Real-time MCE has higher sensitivity in detecting
      coronary stenosis during adenosine triphosphate stress test when compared with
      wall-motion assessment.

PMID- 15562267
TI  - Effect of acute hyperhomocysteinemia on coronary flow reserve in healthy adults.
AB  - BACKGROUND: B-mode ultrasound studies indicate that hyperhomocysteinemia is
      associated with preclinical structural and functional arterial abnormalities.
      This study was designed to evaluate the effect of elevated plasma homocysteine
      levels on coronary flow reserve (CFR). METHODS: A total of 20 healthy subjects
      aged 41 +/- 7 years were studied on 2 separate days, a week apart, before and
      after methionine load (100 mg/kg of body weight) or placebo in a double-blind
      crossover study. At each visit, homocysteine levels were measured by high
      performance liquid chromatography and CFR was determined by transthoracic Doppler
      echocardiography. RESULTS: After methionine load, plasma homocysteine increased
      from 10.7 +/- 2.8 mumol/L to 30.4 +/- 5.1 mumol/L ( P < .0001) and CFR decreased
      from 3.0 +/- 0.4 to 2.3 +/- 0.3 ( P < .001). CFR was inversely related to
      postload homocysteine levels ( r = -0.21, P = .02). After placebo, there was no
      change in CFR. CONCLUSION: In asymptomatic adults, acute hyperhomocysteinemia is
      associated with a significant reduction in CFR.

PMID- 15562268
TI  - Effect of chamber capacitance on Doppler flow pattern across restrictive defects
      in obligatory atrial-level shunts.
AB  - The right atrium has a significantly higher capacitance than the left atrium, and
      this may affect the Doppler flow pattern across an atrial septal defect (ASD) in
      unilateral atrioventricular (AV) valve atresia. This Doppler flow pattern is
      often used to assess ASD adequacy in this setting. We studied the effect of
      atrial capacitance and ASD size on the trans-ASD Doppler flow pattern in an in
      vivo flow model of alternate left or right AV valve atresia (LAVVA and RAVVA). We
      assessed trans-ASD Doppler flow patterns using the max/min velocity ratio and
      mean interatrial pressure gradients (PGs). In both models, ASD flow rate
      correlated with mean trans-ASD PG, but for similar flow rates the slope was
      higher in the LAVVA model. In LAVVA, a persistent PG was consistently observed,
      with low max/min ratio (median, 1.46; range, 1.03-3.13), whereas in RAVVA, phasic
      flow was common (median, 8.0; range, 2.8-20). Because atrial capacitance affects
      mean PG and Doppler flow pattern across the ASD, we propose that the assessment
      of ASD adequacy in RAVVA should not rely on Doppler findings.

PMID- 15562269
TI  - Assessment of intracardiac anomalies in two adults with Ivemark's syndrome.
AB  - Ivemark's syndrome consists of intracardiac anomalies, abnormal lobation of the
      lungs, and abdominal heterotaxy. A frequent intracardiac anomaly seen in
      Ivemark's syndrome is a common atrium, which is associated with left-to-right
      shunting. The increased blood flow and resistance within the pulmonary
      vasculature creates pulmonary hypertension and eventual reversal of the shunt
      physiology. In the absence of additional cyanotic malformations, survival into
      adulthood without prior surgical septation of the common atrium depends on the
      extent of pulmonary hypertension and intracardiac right-to-left shunting. We
      present two patients with a common atrium in the setting of Ivemark's syndrome
      who survived into adulthood without prior operation. Two-dimensional
      echocardiography assessed their intracardiac structures. One patient had right
      atrial isomerism manifested by asplenia and a common atrium, into which the
      hepatic veins drained directly, and the other patient had left atrial isomerism
      manifested by polysplenia, a common atrium, and a ventricular septal defect with
      a single atrioventricular valve. Neither patient had additional cyanotic
      malformations, including obstruction to pulmonary venous return, transposition of
      the great vessels, or pulmonic valve stenosis. The 2-dimensional echocardiogram
      guides the clinician to refer patients for surgical septation of the common
      atrium before the right-to-left shunt physiology predominates. The medical and
      surgical treatment of these patients is discussed.

PMID- 15562270
TI  - A low-cost digital filing system for echocardiography data with MPEG4 compression
      and its application to remote diagnosis.
AB  - The high cost of digital echocardiographs and the large size of data files hinder
      the adoption of remote diagnosis of digitized echocardiography data. We have
      developed a low-cost digital filing system for echocardiography data. In this
      system, data from a conventional analog echocardiograph are captured using a
      personal computer (PC) equipped with an analog-to-digital converter board. Motion
      picture data are promptly compressed using a moving pictures expert group (MPEG)
      4 codec. The digitized data with preliminary reports obtained in a rural hospital
      are then sent to cardiologists at distant urban general hospitals via the
      internet. The cardiologists can evaluate the data using widely available movie
      viewing software (Windows Media Player). The diagnostic accuracy of this double
      check system was confirmed by comparison with ordinary super-VHS videotapes. We
      have demonstrated that digitization of echocardiography data from a conventional
      analog echocardiograph and MPEG 4 compression can be performed using an ordinary
      PC-based system, and that this system enables highly efficient digital storage
      and remote diagnosis at low cost.

PMID- 15562271
TI  - Echocardiographic evaluation of left superior vena cava to the left atrium.
AB  - We report two cases of left superior vena cava draining directly to the left
      atrium in the absence of complex congenital heart disease. This is a rare finding
      causing a decrease in patient oxygen saturations. The location and diagnosis of
      this systemic venous anomaly requires diligence on the part of the cardiac
      sonographer, who should be able to identify the structure during the course of a
      thorough echocardiographic examination. Both adult and pediatric cardiac
      sonographers should be alerted to the possible presence of this vessel. Once the
      vessel has been successfully identified, repair and follow-up are relatively
      simple with positive patient prognosis.

PMID- 15562272
TI  - The use of M-mode echocardiography to identify the true lumen in aortic
      dissection.

PMID- 15562273
TI  - Cardiac lipoma: a rare cause of right-to-left interatrial shunt with normal
      pulmonary artery pressure.
AB  - Cardiac lipomas are rare tumors. They usually remain asymptomatic for a long time
      and cause angina, arrhythmia, dysfunction of the ventricles or valves, and
      peripheral embolization during the later stages of development. There is little
      or no information about right-to-left interatrial shunt with normal pulmonary
      artery pressure, produced as a consequence of the infiltration of the atrial
      septum, the right atrial wall, and the myocardium because of the presence of fat
      in patients with platypnea-orthodeoxia syndrome. We present a patient with this
      syndrome who was identified through transesophageal echocardiography. The study
      showed a massive right-to-left shunt without pulmonary hypertension, produced by
      an important cardiac infiltration of adipose tissue that created a narrow passage
      in the right atrium, and a redirection of the flow to a patent foramen ovale,
      explaining the pathophysiology of the syndrome.

PMID- 15562274
TI  - Coronary artery fistula presenting as bacterial endocarditis.
AB  - Coronary artery fistula is often considered to be a benign and rare congenital
      anomaly. It is usually an incidental finding encountered during routine cardiac
      catheterization. We report a case of a patient presenting with endocarditis
      involving a large coronary artery fistula connecting an aneurysmal circumflex
      coronary artery to the coronary sinus. The diagnosis was initially made by
      echocardiography and confirmed by cardiac catheterization. In addition, we
      briefly discuss the literature on management of this coronary anomaly.

PMID- 15562275
TI  - Idiopathic sinus of Valsalva to right atrial fistula: an unusual origin of right
      sided heart failure.

PMID- 15562276
TI  - Thrombosed right coronary artery aneurysm presenting as a myocardial mass.
AB  - A coronary artery aneurysm is defined as coronary dilatation that exceeds the
      diameter of normal adjacent artery segments, or is 1.5 times the diameter of the
      largest coronary artery. Coronary artery aneurysms are rare with an incidence of
      between 1.5% to 5%. The aneurysm is caused by destruction of the vessel media,
      thinning of the arterial wall, increased wall stress, and progressive dilatation
      of a segment of the coronary artery. The most common cause is atherosclerotic
      coronary artery disease. These aneurysms occasionally rupture but more commonly
      develop thrombus and hematoma leading to the appearance of the presence of an
      intramyocardial mass. We present the case of a 60-year-old man with hypertension
      who presented with a mass that was identified initially by transthoracic
      echocardiography in the setting of an inferior wall myocardial infarction, which
      was later recognized to be a thrombosed right coronary artery aneurysm.

PMID- 15562280
TI  - Possible role of USP26 in patients with severely impaired spermatogenesis.
AB  - The ubiquitin-specific protease 26 (USP26) gene is an X-linked gene specifically
      expressed in testis tissue. This gene is therefore a potential infertility gene.
      In order to analyse its possible involvement in spermatogenesis and infertility,
      42 patients with Sertoli cell-only syndrome were analysed for mutations in this
      gene. We found four patients with exactly the same three changes of the
      nucleotide and therefore also amino acid sequence. These patients showed 370
      371insACA, 494T>C and 1423C>T causing T123-124ins, L165S and H475Y, respectively.
      These changes were not found in 10 control samples. Furthermore, two
      polymorphisms were observed which do not alter the amino-acid sequence. A
      restriction analysis that can make a distinction between a T and a C, at position
      494, was set up in order to examine more patient and control samples. Another 69
      patients with Sertoli cell-only syndrome, 32 patients with maturation arrest and
      142 control samples were analysed using this method. None of the control samples
      or patients with maturation arrest featured the change at position 494. However,
      four more patients with Sertoli cell-only syndrome were identified with the three
      alterations. The frequency of alterations in this group is therefore 7.2%
      (8/111). One of the patients had a deletion of the long arm of the Y chromosome,
      while another patient had a varicocoele. These results indicate that these
      alterations might be involved in male infertility or might increase the risk of
      male infertility.

PMID- 15562281
TI  - A neurological phenotype in nail patella syndrome (NPS) patients illuminated by
      studies of murine Lmx1b expression.
AB  - Nail patella syndrome (NPS) is an autosomal dominant disorder affecting
      development of the limb, kidney and eye. NPS is the result of heterozygous loss
      of-function mutations in the LIM-homeodomain transcription factor, LMX1B. Recent
      studies suggest that the NPS phenotype may be more extensive than recognized
      previously including neurologic and neurobehavioral aspects. To determine whether
      these findings correlated with the expression of Lmx1b during development, an
      internal ribosomal entry site-LacZ reporter was inserted into the 3'UTR of the
      endogenous murine gene. The pattern of Lmx1b expression during the development of
      the limb, eye and kidney correlates with the NPS phenotype. Additional sites of
      expression were observed in the central nervous system (CNS). The effects of the
      absence of Lmx1b in the CNS were determined in lmx1b-/- mice by histology and
      immunocytochemistry. Lmx1b is required for the differentiation and migration of
      neurons within the dorsal spinal cord. The inability of afferent sensory neurons
      to migrate into the dorsal horn is entirely consistent with diminished pain
      responses in NPS patients.

PMID- 15562282
TI  - FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene.
AB  - We describe a new member of the human Factor H protein family, termed Factor H
      related protein 4A (FHR-4A). The corresponding cDNA sequence was isolated and
      encodes a secreted protein of 559 amino acids, with a predicted molecular weight
      of 63.2 kDa. Apparently, this novel cDNA is derived from the human FHR-4 gene.
      Genetic analysis shows that the human FHR-4 gene is composed of 10 coding exons,
      and two distinct mRNA transcripts are derived from this gene by alternative
      splicing. The short FHR-4B form represents a truncated variant and encodes a
      secreted protein of five domains (previously termed FHR-4). The long transcript
      encodes the novel FHR-4A protein that is composed of nine complement control
      protein (CCP) domains. A unique feature of FHR-4A is the tandem arrangement of
      four CCP domains forming a 'natural dimer' of the short isoform. The FHR-4A
      protein is identified in human plasma as a 86 kDa protein. The difference between
      the predicted and observed molecular masses is explained by glycosylation.
      Comparison of the deduced protein sequence of FHR-4A with peptides from a 86 kDa
      apolipoprotein described by us earlier suggests that the long form, FHR-4A,
      represents this apoprotein. In summary, FHR-4A is a new Factor H-related protein
      with a unique domain composition, that is, an internal duplication of four CCP
      domains. To our knowledge, FHR-4A provides the first evidence for alternative
      splicing among Factor H-related genes.

PMID- 15562283
TI  - Novel length variant of the polypyrimidine tract within the splice acceptor site
      in intron 8 of the CFTR gene: consequences for genetic testing using standard
      assays.

PMID- 15562284
TI  - Is group selection necessary to explain social adaptations in microorganisms?

PMID- 15562285
TI  - Genetic isolation between two sympatric host plant races of the European corn
      borer, Ostrinia nubilalis Hubner. II: assortative mating and host-plant
      preferences for oviposition.
AB  - The European corn borer, Ostrinia nubilalis Hubner, colonized maize (Zea mays L.)
      after its introduction into Europe about 500 years ago and is now considered one
      of the main pests of this crop. In northern France, two sympatric host races have
      been described: one feeding on maize and the other on mugwort (Artemisia vulgaris
      L.) and hop (Humulus lupulus L.). In a previous study, we showed that mating
      between the two races may be impeded by differences in the timing of moth
      emergence and in the composition of the sex pheromone produced by the females. In
      this study, we further investigated the genetic isolation of these two races
      using strains from the maize (Z strain) and mugwort (E strain) races selected for
      diagnostic alleles at two allozyme loci. In a cage containing maize and mugwort
      plants and located in natural conditions, mating between individuals of the same
      strain occurred more often than mating between males and females of the E and Z
      strains. In particular, we obtained no evidence for crosses between Z females and
      E males. We also found that females of the Z strain laid their eggs almost
      exclusively on maize, whereas females of the E strain laid their eggs
      preferentially, but not exclusively, on mugwort. These results suggest that the
      genetic differentiation between the two host races may also be favored by host
      plant preference, one of the first steps toward sympatric speciation.

PMID- 15562286
TI  - Effects of gibberellin mutations on tolerance to apical meristem damage in
      Arabidopsis thaliana.
AB  - To examine the role of gibberellin hormones (GAs) in tolerance to apical meristem
      damage (AMD), we characterized the reaction norms of several GA-deficient and
      insensitive mutants of Arabidopsis thaliana in response to AMD and compared them
      to those of the wild type, Landsberg, from which they were derived. We included
      'natural' genotypes of A. thaliana--accessions with shorter lab histories--in
      order to evaluate how representative Landsberg is of other genotypes. The GA
      mutations did not alter the level of tolerance to AMD, which was consistent with
      equal compensation for all genotypes. Generally, the reaction norms to AMD did
      not differ among the GA mutants themselves, or between the GA mutants and
      Landsberg. The GA mutations did affect the overall phenotypes of the plants, but
      these effects were not simply related to whether the mutation was early or late
      in the biochemical pathways. The GA-insensitive mutant was phenotypically
      different from the GA-deficient mutants and from Landsberg. The natural
      populations differed significantly from Landsberg, particularly in attributes
      related to size and inflorescence production, one more example of the need for
      researchers to be careful when generalizing the results of studies based upon
      laboratory strains. Our results indicate that early-flowering genotypes of A.
      thaliana can be remarkably tolerant to AMD, and that GA deficiency/insensitivity
      does not hinder tolerance to AMD, at least in this genetic background. Moreover,
      we confirm that mutations at regulatory loci can have noncatastrophic effects on
      fitness, as recently found by other investigators.

PMID- 15562287
TI  - Multiple infections and diversity of cytoplasmic incompatibility in a
      haplodiploid species.
AB  - Cytoplasmic incompatibility (CI) is a sperm-egg incompatibility commonly induced
      by the intracellular endosymbiont bacterium Wolbachia that, in diploid species,
      results in embryo mortality. In haplodiploid species, two types of CI exist
      depending on whether the incompatible fertilized eggs develop into males (male
      development (MD)) or abort (female mortality (FM)). CI allows multiple infections
      to be maintained in host populations, and thus allows interactions to occur
      between co-infecting strains. In Leptopilina heterotoma, three Wolbachia strains
      coexist naturally (wLhet1, wLhet2, wLhet3). When these three strains are all
      present, they induce a CI of FM type, whereas wLhet1 alone expresses a CI
      phenotype intermediate between MD and FM. Here, we compare CI effects in crosses
      involving insect lines sharing the same nuclear background, but harboring
      different mixtures of strains. Mating experiments showed that: (i) wLhet2 and
      wLhet3 also induce an intermediate CI when acting alone, and show a bidirectional
      incompatibility; (ii) there is no interaction between the co-infecting strains in
      CI expression; (iii) the diversity of Wolbachia present within a male host
      influences the expression of CI: an increase in the number of strains is
      correlated with a decrease in the proportion of the MD type, which is also
      correlated with an increase in bacterial density. All these data suggest that the
      CI of FM type results from a stronger effect than the MD type, which conflicts
      with the conventional hypotheses used to explain CI diversity in haplodiploids,
      and could provide some new information about CI mechanisms in insects.

PMID- 15562288
TI  - Karyotypic diversity and evolution of Loricariidae (Pisces, Siluriformes).
AB  - We present cytogenetic analyses of four fish species, belonging to four
      Loricariidae subfamilies: Neoplecostomus microps (Neoplecostominae) with 2n=54
      chromosomes, Harttia loricariformis (Loricariinae) with 2n=56 chromosomes,
      Hypostomus affinis (Hypostominae) with 2n=66 chromosomes and Upsilodus sp.
      (Upsilodinae), with 2n=96 chromosomes. In addition to karyotypes, data on the
      location of 18s rDNA sites are presented, derived from indirect (silver nitrate
      impregnation) and direct (FISH) methods. There is only one pair of nucleolar
      organizing regions (NORs) per species, except in H. affinis. Diversity and NOR
      macrokaryotypic evolution in the species analyzed are discussed in relation to
      the evolution of the Loricariidae as a whole. In addition, a revision of the
      cytogenetic data available for this family is presented.

PMID- 15562289
TI  - Inbreeding depression in self-incompatible and self-compatible populations of
      Leavenworthia alabamica.
AB  - Inbreeding depression is one of the leading factors preventing the evolution of
      self-fertilization in plants. In populations where self-fertilization evolves,
      theory suggests that natural selection against partially recessive deleterious
      alleles will reduce inbreeding depression. The purpose of this study was to
      evaluate this hypothesis by comparing the magnitude of inbreeding depression in
      self-incompatible and self-compatible populations of Leavenworthia alabamica.
      Within-population crosses were conducted to compare the quantity and quality of
      offspring produced by outcrossing and self-fertilization. These progeny were
      grown in a common greenhouse and inbreeding depression was measured in
      germination, survival, biomass, transition rate to flowering, flower number,
      petal length, pollen grains/anther, pollen viability, and ovule number. In
      comparison to outcrossing, self-fertilization led to the production of fewer and
      smaller seeds within self-incompatible populations. Moreover, inbreeding
      depression was observed in eight of 11 offspring traits within self-incompatible
      populations of L. alabamica. In contrast, there was significant inbreeding
      depression only in flower number within self-compatible populations. The results
      of this study are consistent with the idea that self-fertilization selectively
      removes partially recessive deleterious alleles causing inbreeding depression in
      natural plant populations. However, in plant species such as L. alabamica where
      self-compatibility may evolve in small populations following long-distance
      dispersal, declines in inbreeding depression may also be facilitated by genetic
      drift.

PMID- 15562290
TI  - Breast milk and lipid intake distributions for assessing cumulative exposure and
      risk.
AB  - Breast milk consumption is the primary route of infant exposure to certain
      lipophilic toxicants that have accumulated over decades in maternal adipose
      tissue, as well as to less persistent toxicants from maternal exposure during
      lactation. Such infant exposures occur at a time of rapid growth and development
      when susceptibility to certain toxicants can be greatest. Breast milk and lipid
      intake rates are presented for the 0-6 and 0-12 month age periods for infants fed
      according to the American Academy of Pediatrics' current recommendations
      (exclusive breast-feeding for 0-6 months and continued breast-feeding to 12
      months). Intake rates are normalized to infant bodyweight to account for the
      covariance of consumption and bodyweight. Frequency distributions describe the
      population variability in intake. For age 0-12 months, daily average milk intake
      is 100.7 +/- 22.7 g/kg day (mean +/- SD), with a 95th percentile of 153.5 g/kg
      day. Breast milk intake distributions are also developed for infants exclusively
      breast-fed (no significant calories from non-breast milk sources) over their
      first year, and for the entire (nursing and non-nursing) infant population. For
      short-term exposures, intake can be derived from the regression equation
      presented here. Lipid intake estimated assuming a 4% lipid content (current risk
      assessment practice) is compared and found comparable to that derived from
      measured lipid content. The national trend of increased breast-feeding found in
      surveys further supports including the breast milk pathway in risk assessment.

PMID- 15562291
TI  - Adoption of an official ISEA glossary.
AB  - The International Society for Exposure Analysis (ISEA) and its Nomenclature
      Committee have been involved since the mid-1990s in an intermittent but ongoing
      effort to develop an official ISEA glossary. Several related activities have
      stimulated greater interest and discussion nationally and internationally on a
      common exposure language. Among these activities are a 1997 Journal of Exposure
      Analysis and Environmental Epidemiology feature article on exposure and dose
      definitions and a 1999-initiated project of the International Programme on
      Chemical Safety (IPCS) (WHO/ILO/UNEP) to confront terminology issues hindering
      harmonization in the area of exposure assessment. Recently, the ISEA members
      voted in support of adopting the IPCS glossary as the official ISEA glossary, and
      the ISEA Executive Board agreed to accept this recommendation. In this feature
      article, we (1) describe the process through which the ISEA adopted the IPCS
      glossary as the official ISEA glossary, (2) present the joint IPCS/ISEA glossary
      of terms and their definitions, and (3) discuss plans for how the glossary can be
      used by ISEA and updated over time by ISEA and IPCS. The glossary is intended to
      be a living document that reflects the latest usage and maintains international
      harmonization of exposure terminology that can be practically applied to improve
      communication in exposure and related fields.

PMID- 15562292
TI  - Disruption of brain white matter microstructure by excessive intracellular and
      extracellular fluid in alcoholism: evidence from diffusion tensor imaging.
AB  - Magnetic resonance diffusion tensor imaging (DTI) has revealed the disruption of
      brain white matter microstructure in normal aging and alcoholism undetectable
      with conventional structural MR imaging. The metrics of DTI can be useful in
      establishing the nature of the observed microstructural aberrations. Abnormally
      low fractional anisotropy (FA), a measure of diffusion orientation and coherence,
      may result from increased intracellular or extracellular fluid, which would be
      reflected in complementary high apparent diffusion coefficients (bulk mean
      diffusivity) and low FA, or from disorganization of fiber structure, which would
      be reflected in low FA but with a lack of the inverse FA and diffusivity
      relationship. To test these competing possibilities, we examined 15 alcoholic men
      and 31 control men with DTI to quantify diffusivity in the genu and splenium of
      the corpus callosum and centrum semiovale. In addition to the previously observed
      FA deficits in all the three brain regions, the alcoholics had abnormally high
      white matter diffusivity values in the genu and centrum. Further, inverse
      correlations between FA and diffusivity were significant in the genu (r=-0.52,
      p<0.05) and centrum (r=-0.92, p=0.0001). Multiple regression analyses examining
      diffusivity and age as predictors of FA identified diffusivity as a significant
      unique contributor to FA in both regions. These results suggest that decreased
      orientational coherence of brain white matter in alcoholism is attributable, at
      least in part, to the accumulation of intracellular and extracellular fluid in
      excess of that occurring in aging, and that the differential influence of these
      fluid compartments can vary across brain regions.

PMID- 15562293
TI  - Dopamine D3 receptor ligands block nicotine-induced conditioned place preferences
      through a mechanism that does not involve discriminative-stimulus or
      antidepressant-like effects.
AB  - Environmental stimuli previously paired with drug taking appear to play a
      critical role in nicotine dependence. Converging anatomical, pharmacological, and
      behavioral evidence implicates dopamine D3 receptors (D3Rs) in the mechanisms
      underlying stimulus-controlled drug-seeking behavior. This study assessed the
      effects of BP 897, a D3R partial agonist and ST 198, a D3R antagonist, on
      nicotine-induced conditioned place preferences (CPPs), used as a measure of drug
      seeking behavior, on food-maintained responding and on discrimination performance
      under a two-lever-choice nicotine discrimination procedure. BP 897 and ST 198
      both blocked the expression of nicotine-induced CPP at doses selective for D3R.
      They had no effect on locomotor activity in the CPP apparatus and no significant
      effect on nicotine discrimination performance or food-maintained responding under
      the discrimination procedure. Involvement of antidepressant actions in the
      effects of BP 897 and ST 198 on CPP is unlikely, since we found no effect of D3R
      blockade with BP 897 or genetic depletion of D3Rs in a forced swimming test, used
      as a behavioral test for antidepressant activity. This suggests that D3R ligands
      reduce the motivational effects of nicotine by a mechanism distinct from those of
      nicotine replacement therapy and bupropion, the two currently used aids for
      smoking cessation in humans. These findings support the use of D3R ligands as
      aids for smoking cessation and indicate that their effects would be selective for
      those rewarding or reinforcing effects of nicotine that contribute to the
      maintenance of tobacco-smoking behavior, without affecting subjective responses
      to nicotine or producing any antidepressant-like effects.

PMID- 15562294
TI  - Activation of TRPV1 in the VTA excites dopaminergic neurons and increases
      chemical- and noxious-induced dopamine release in the nucleus accumbens.
AB  - Dopamine (DA)-containing neurons of the ventral tegmental area (VTA) provide
      dopaminergic input to the nucleus accumbens and to the prefrontal cortex within
      the mesolimbic pathway. In the present study, we combined electrophysiological
      recordings and microdialysis techniques to investigate the function of transient
      receptor potential vanilloid 1 (TRPV1) channel in the VTA. In brain slices,
      application of the TRPV1 receptor agonist capsaicin increased the firing rate of
      rat dopamine neurons and in a proportion of tested cells (44%) it also induced a
      bursting behavior. The effects of capsaicin were concentration dependent. The
      increase in neuronal firing was dependent on enhanced glutamatergic transmission
      since it was blocked by the superfusion of the ionotropic glutamate antagonists,
      CNQX and AP5. Interestingly, microinjection of capsaicin into the VTA and noxious
      tail stimulation transiently enhanced dopamine release into the nucleus
      accumbens. Both the in vitro and in vivo effects were mediated by TRPV1
      activation in the VTA since they were reduced by co-perfusion of the selective
      TRPV1 receptor antagonist iodoresineferatoxin. Our data suggest a novel role for
      TRPV1 channels in the mesencephalon of rat, namely activation of the DA system
      following a peripheral noxious stimulation.

PMID- 15562295
TI  - Chronic lithium administration to rats selectively modifies 5-HT2A/2C receptor
      mediated brain signaling via arachidonic acid.
AB  - The effects of chronic lithium administration on regional brain incorporation
      coefficients k* of arachidonic acid (AA), a marker of phospholipase A2 (PLA2)
      activation, were determined in unanesthetized rats administered i.p. saline or 1
      mg/kg i.p. (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride
      (DOI), a 5-HT2A/2C receptor agonist. After injecting [1-(14)C]AA intravenously,
      k* (brain radioactivity/integrated plasma radioactivity) was measured in each of
      94 brain regions by quantitative autoradiography. Studies were performed in rats
      fed a LiCl or a control diet for 6 weeks. In the control diet rats, DOI
      significantly increased k* in widespread brain areas containing 5-HT2A/2C
      receptors. In the LiCl-fed rats, the significant positive k* response to DOI did
      not differ from that in control diet rats in most brain regions, except in
      auditory and visual areas, where the response was absent. LiCl did not change the
      head turning response to DOI seen in control rats. In summary, LiCl feeding
      blocked PLA2-mediated signal involving AA in response to DOI in visual and
      auditory regions, but not generally elsewhere. These selective effects may be
      related to lithium's therapeutic efficacy in patients with bipolar disorder,
      particularly its ability to ameliorate hallucinations in that disease.

PMID- 15562296
TI  - Bilateral lesions of the habenula induce attentional disturbances in rats.
AB  - The habenular nuclear complex is a major influence on brainstem cell groups that
      influence attention, but its role in attentional performance has not previously
      been explored. The present study investigated how habenula lesions affect
      attentional function as assessed by the 5-choice serial reaction time task (5
      CSRTT) in male Lister-Hooded rats. Rats were pretrained in the 5-CSRTT before
      receiving discrete bilateral lesions of the habenula or a sham procedure. In test
      sessions immediately following recovery from surgery, lesioned rats showed a
      marked increase in premature responding. Over the course of testing this increase
      of premature responding declined in magnitude. In contrast, choice accuracy
      showed no impairment during the earliest postsurgery test sessions but
      progressively deteriorated over the course of testing. These opposite time
      courses strongly imply that different mechanisms mediate these two effects of the
      habenula lesion. Differential effects of drug treatment on these effects further
      supported this view. Thus, D-amphetamine (0.2 mg/kg s.c.) increased premature
      responding without affecting choice accuracy. On the other hand, haloperidol
      (0.01-0.03 mg/kg i.p.) decreased premature responding without significantly
      affecting choice accuracy. The results are consistent with the view that elevated
      premature responding in habenula-lesioned animals is mediated by increased
      dopaminergic activity, whereas impaired choice accuracy is not. Implications of
      these findings for the hypothesis that habenula dysfunction is involved in
      cognitive symptoms of schizophrenia are discussed.

PMID- 15562297
TI  - The effect of clozapine on extracellular dopamine levels in the shell subregion
      of the rat nucleus accumbens is reversed following chronic administration:
      comparison with a selective 5-HT(2C) receptor antagonist.
AB  - The clinical onset of both the therapeutic and side effects of antipsychotic
      drugs can take days/weeks to develop. Therefore, it is likely that adaptive
      changes in neurotransmission of key systems may only manifest upon chronic
      administration. Thus, using in vivo microdialysis we have evaluated the acute and
      chronic (21 days) effects of the atypical antipsychotic clozapine on nucleus
      accumbens (NAcc) dopamine (DA) output in the rat. Clozapine (10 mg/kg p.o.)
      produced an acute 60% increase in extracellular levels of DA in the shell but not
      the core subregion of the NAcc. This clozapine-induced effect was also apparent
      on day 8 (59% increase) of chronic administration. However, on day 22 (following
      21 days chronic administration), clozapine-induced a significant decrease in
      extracellular DA levels (44% decrease). Since clozapine possesses significant
      affinity for the 5-HT(2C) receptor these clozapine-induced effects were compared
      to those of SB-243213, a selective 5-HT(2C) receptor antagonist. SB-243213 (10
      mg/kg p.o.) had no effect on NAcc DA levels either acutely or following 21 days
      chronic administration. These data demonstrate that the atypical neuroleptic
      clozapine is more effective at eliciting changes in the shell vs the core
      subregion of the NAcc. In contrast, chronic treatment produces a time-dependent
      reduction in clozapine-induced DA efflux in the shell subregion. This selective
      temporal change in dopaminergic neurotransmission may be associated with the
      delayed therapeutic onset of antipsychotic activity. However, since SB-243213 had
      no effect on DA levels in the NAcc, it is likely that 5-HT(2C) receptor
      antagonism alone is not the mechanism by which clozapine exerts is actions.

PMID- 15562298
TI  - Synthesis, Purification and Crystallization of Guanine-rich RNA Oligonucleotides.
AB  - Guanine-rich RNA oligonucleotides display many novel structural motifs in recent
      crystal structures. Here we describe the procedures of the chemical synthesis and
      the purification of such RNA molecules that are suitable for X-ray
      crystallographic studies. Modifications of the previous purification methods
      allow us to obtain better yields in shorter time. We also provide 24 screening
      conditions that are very effective in crystallization of the guanine-rich RNA
      oligonucleotides. Optimal crystallization conditions are usually achieved by
      adjustment of the concentration of the metal ions and pH of the buffer. Crystals
      obtained by this method usually diffract to high resolution.

PMID- 15562299
TI  - Effects of Seizures on Autonomic and Cardiovascular Function.
AB  - Parial and generalized seizures often affect autonomic function during seizures
      as well as during the interictal and postictal periods. Activation or inhibition
      of areas in the central autonomic network can cause cardiovascular,
      gastrointestinal, cutaneous, pupillary, urinary, and genital manifestations.
      Autonomic dysfunction during or after seizures may cause cardiac and pulmonary
      changes that contribute to sudden unexplained death in epilepsy.

PMID- 15562300
TI  - Epilepsy Surgery: Are You Ever out of the Woods?

PMID- 15562301
TI  - Refractory Familial TLE Responds Favorably to Surgical Intervention.

PMID- 15562302
TI  - Do Immediate Postoperative Seizures Predict Surgical Failure After Frontal Lobe
      Epilepsy Surgery?

PMID- 15562303
TI  - EEG 24/7: The Use of Emergency EEG to Diagnose Status Epilepticus.

PMID- 15562304
TI  - Distinguishing Lateral Temporal Neocortical and Mesial Temporal Lobe Epilepsy.

PMID- 15562305
TI  - Thalamic Dysfunction in Idiopathic Generalized Epilepsy: New Findings of Old
      News.

PMID- 15562306
TI  - What Valproate Does and Doesn't Do.

PMID- 15562307
TI  - Losigamone: Another Novel Drug for Partial Seizures.

PMID- 15562308
TI  - Inherited Channelopathies Associated with Epilepsy.
AB  - Ion channels are critical for neuronal excitability and provide important targets
      for anticonvulsant drugs. In the past few years, several monogenetic epilepsies
      have been linked to mutations in genes encoding either voltage-gated or ligand
      gated channels. The recognition that certain epilepsy syndromes are
      "channelopathies" initiates a new era in understanding the molecular
      pathophysiology of seizure disorders. This review summarizes recent advances
      related to this exciting area of investigation.

PMID- 15562309
TI  - Hyperpolarization-activated Cation Channels in Human and Experimental Epilepsy:
      Do They Play a Role in Epileptogenesis?

PMID- 15562310
TI  - Brain Inflammation and Seizures.

PMID- 15562311
TI  - Endocannabinoid Effects on Febrile Seizures: Not Just a Toke(n) Mechanism.

PMID- 15562312
TI  - Denervation and Reinnervation of Amygdaloid Neurons in Drug-refractory Temporal
      Lobe Epilepsy.

PMID- 15562313
TI  - Gap Junctions in Epileptogenesis: Chicken or Egg?

PMID- 15562314
TI  - A Second Gene for Lafora Disease.

PMID- 15562315
TI  - In silico reconstitution of Listeria propulsion exhibits nano-saltation.
AB  - To understand how the actin-polymerization-mediated movements in cells emerge
      from myriad individual protein-protein interactions, we developed a computational
      model of Listeria monocytogenes propulsion that explicitly simulates a large
      number of monomer-scale biochemical and mechanical interactions. The literature
      on actin networks and L. monocytogenes motility provides the foundation for a
      realistic mathematical/computer simulation, because most of the key rate
      constants governing actin network dynamics have been measured. We use a cluster
      of 80 Linux processors and our own suite of simulation and analysis software to
      characterize salient features of bacterial motion. Our "in silico reconstitution"
      produces qualitatively realistic bacterial motion with regard to speed and
      persistence of motion and actin tail morphology. The model also produces smaller
      scale emergent behavior; we demonstrate how the observed nano-saltatory motion of
      L. monocytogenes,in which runs punctuate pauses, can emerge from a cooperative
      binding and breaking of attachments between actin filaments and the bacterium. We
      describe our modeling methodology in detail, as it is likely to be useful for
      understanding any subcellular system in which the dynamics of many simple
      interactions lead to complex emergent behavior, e.g., lamellipodia and filopodia
      extension, cellular organization, and cytokinesis.

PMID- 15562316
TI  - Secreted Bacterial Effectors and Host-Produced Eiger/TNF Drive Death in
      aSalmonella-Infected Fruit Fly.
AB  - Death by infection is often as much due to the host's reaction as it is to the
      direct result of microbial action. Here we identify genes in both the host and
      microbe that are involved in the pathogenesis of infection and disease in
      Drosophila melanogaster challenged with Salmonella enterica serovartyphimurium
      (S. typhimurium). We demonstrate that wild-typeS. typhimurium causes a lethal
      systemic infection when injected into the hemocoel of D. melanogaster. Deletion
      of the gene encoding the secreted bacterial effect or Salmonella leucine-rich
      (PslrP)changes an acute and lethal infection to one that is persistent and less
      deadly. We propose a model in which Salmonella secreted effectors stimulate the
      fly and thus cause an immune response that is damaging both to the bacteria and,
      subsequently, to the host. In support of this model, we show that mutations in
      the fly gene eiger, a TNF homolog, delay the lethality of Salmonella infection.
      These results suggest that S. typhimurium-infected flies die from a condition
      that resembles TNF-induced metabolic collapse in vertebrates. This idea provides
      us with a new model to study shock-like biology in a genetically manipulable
      host. In addition, it allows us to study the difference in pathways followed by a
      microbe when producing an acute or persistent infection.

PMID- 15562317
TI  - Modern humans did not admix with Neanderthals during their range expansion into
      Europe.
AB  - The process by which the Neanderthals were replaced by modern humans between
      42,000 and 30,000 before present is still intriguing. Although no Neanderthal
      mitochondrial DNA (mtDNA) lineage is found to date among several thousands of
      Europeans and in seven early modern Europeans, interbreeding rates as high as 25%
      could not be excluded between the two subspecies. In this study, we introduce a
      realistic model of the range expansion of early modern humans into Europe, and of
      their competition and potential admixture with local Neanderthals. Under this
      scenario, which explicitly models the dynamics of Neanderthals' replacement, we
      estimate that maximum interbreeding rates between the two populations should have
      been smaller than 0.1%. We indeed show that the absence of Neanderthal mtDNA
      sequences in Europe is compatible with at most 120 admixture events between the
      two populations despite a likely cohabitation time of more than 12,000 y. This
      extremely low number strongly suggests an almost complete sterility between
      Neanderthal females and modern human males, implying that the two populations
      were probably distinct biological species.

PMID- 15562318
TI  - Patterns of intron gain and loss in fungi.
AB  - Little is known about the patterns of intron gain and loss or the relative
      contributions of these two processes to gene evolution. To investigate the
      dynamics of intron evolution, we analyzed orthologous genes from four filamentous
      fungal genomes and determined the pattern of intron conservation. We developed a
      probabilistic model to estimate the most likely rates of intron gain and loss
      giving rise to these observed conservation patterns. Our data reveal the
      surprising importance of intron gain. Between about 150 and 250 gains and between
      150 and 350 losses were inferred in each lineage. We discuss one gene in
      particular (encoding 1-phosphoribosyl-5-pyrophosphate synthetase) that displays
      an unusually high rate of intron gain in multiple lineages. It has been
      recognized that introns are biased towards the 5' ends of genes in intron-poor
      genomes but are evenly distributed in intron-rich genomes. Current models
      attribute this bias to 3' intron loss through a poly-adenosine-primed reverse
      transcription mechanism. Contrary to standard models, we find no increased
      frequency of intron loss toward the 3' ends of genes. Thus, recent intron
      dynamics do not support a model whereby 5' intron positional bias is generated
      solely by 3'-biased intron loss.

PMID- 15562319
TI  - A transcriptional profile of aging in the human kidney.
AB  - In this study, we found 985 genes that change expression in the cortex and the
      medulla of the kidney with age. Some of the genes whose transcripts increase in
      abundance with age are known to be specifically expressed in immune cells,
      suggesting that immune surveillance or inflammation increases with age. The age
      regulated genes show a similar aging profile in the cortex and the medulla,
      suggesting a common underlying mechanism for aging. Expression profiles of these
      age-regulated genes mark not only age, but also the relative health and
      physiology of the kidney in older individuals. Finally, the set of aging
      regulated kidney genes suggests specific mechanisms and pathways that may play a
      role in kidney degeneration with age.

PMID- 15562320
TI  - Drosophila spastin regulates synaptic microtubule networks and is required for
      normal motor function.
AB  - The most common form of human autosomal dominant hereditary spastic paraplegia
      (AD-HSP) is caused by mutations in the SPG4 (spastin) gene, which encodes an AAA
      ATPase closely related in sequence to the microtubule-severing protein Katanin.
      Patients with AD-HSP exhibit degeneration of the distal regions of the longest
      axons in the spinal cord. Loss-of-function mutations in the Drosophila spastin
      gene produce larval neuromuscular junction (NMJ) phenotypes. NMJ synaptic boutons
      in spastin mutants are more numerous and more clustered than in wild-type, and
      transmitter release is impaired. spastin-null adult flies have severe movement
      defects. They do not fly or jump, they climb poorly, and they have short
      lifespans. spastin hypomorphs have weaker behavioral phenotypes. Overexpression
      of Spastin erases the muscle microtubule network. This gain-of-function phenotype
      is consistent with the hypothesis that Spastin has microtubule-severing activity,
      and implies that spastin loss-of-function mutants should have an increased number
      of microtubules. Surprisingly, however, we observed the opposite phenotype: in
      spastin-null mutants, there are fewer microtubule bundles within the NMJ,
      especially in its distal boutons. The Drosophila NMJ is a glutamatergic synapse
      that resembles excitatory synapses in the mammalian spinal cord, so the reduction
      of organized presynaptic microtubules that we observe in spastin mutants may be
      relevant to an understanding of human Spastin's role in maintenance of axon
      terminals in the spinal cord.

PMID- 15562322
TI  - A taxpayer-funded clinical trials registry and results database.

PMID- 15562321
TI  - Replication of Norovirus in cell culture reveals a tropism for dendritic cells
      and macrophages.
AB  - Noroviruses are understudied because these important enteric pathogens have not
      been cultured to date. We found that the norovirus murine norovirus 1 (MNV-1)
      infects macrophage-like cells in vivo and replicates in cultured primary
      dendritic cells and macrophages. MNV-1 growth was inhibited by the interferon
      alphabeta receptor and STAT-1, and was associated with extensive rearrangements
      of intracellular membranes. An amino acid substitution in the capsid protein of
      serially passaged MNV-1 was associated with virulence attenuation in vivo. This
      is the first report of replication of a norovirus in cell culture. The capacity
      of MNV-1 to replicate in a STAT-1-regulated fashion and the unexpected tropism of
      a norovirus for cells of the hematopoietic lineage provide important insights
      into norovirus biology.

PMID- 15562323
TI  - Reflections on the withdrawal of rofecoxib.

PMID- 15562324
TI  - Analysis of spatial and temporal evolution of vegetation cover in the Spanish
      Central Pyrenees: role of human management.
AB  - A vegetation cover increase has been identified at global scales using satellite
      images and vegetation indices. This fact is usually explained by global climatic
      change processes such as CO(2) and temperature increases. Nevertheless, although
      these causes can be important, the role of socioeconomic transformations must be
      considered in some places, since in several areas of Northern Hemisphere an
      important change in management practices has been detected. Rural depopulation
      and land abandonment have reactivated the natural vegetation regeneration
      processes. This work analyses the vegetation evolution in the central Spanish
      Pyrenees from 1982 to 2000. The analysis has been done by using calibrated-NDVI
      temporal series from NOAA-AVHRR images. A positive and significant trend in NDVI
      data has been identified from 1982 to 2000 coinciding with a temperature increase
      in the study area. However, the spatial differences in magnitude and the sign of
      NDVI trends are significant. The role of land management changes in the 20th
      century is considered as a hypothesis to explain the spatial differences in NDVI
      trends. The role of land-cover and human land-uses on this process has been
      analyzed. The highest increment of NDVI is detected in lands affected by
      abandonment and human extensification. The importance of management changes in
      vegetation growth is discussed, and we indicate that although climate has great
      importance in vegetal evolution, land-management changes can not be neglected in
      our study area.

PMID- 15562325
TI  - Phage Display Technologies - SMi Conference. 23-24 January 2002, London, UK.
AB  - This fairly small meeting, with about 50 attendees, covered all areas of antibody
      engineering from basic technologies to applications in both therapeutic and
      diagnostic areas. Despite the fact that nearly all speakers came from commercial
      organizations, the data presented were solid and highly informative. While new
      technologies, such as yeast or ribosome display, are integrating into the drug
      discovery process, vaccine technology looks like a promising alternative to human
      antibody therapy. New advances in the field, especially in technology, are
      primarily governed by the tight intellectual property situation.

PMID- 15562326
TI  - Macrolides, azalides, streptogramins, ketolides and oxazolidinones - sixth annual
      international conference. 24-25 January 2002, Bologna, Italy.

PMID- 15562327
TI  - Clinical gene therapy - first international conference. 24-26 January 2002,
      Groningen, the Netherlands.
AB  - The first International Conference on Clinical Gene Therapy focused primarily on
      gene therapy for cardiovascular disorders, genetic diseases (hemophilia, cystic
      fibrosis) and cancer, with particular emphasis on clinical trials and advanced
      preclinical studies. Recent improvements in vector technologies led to the first
      demonstration that gene therapy could cure a disease in a clinically relevant
      animal model of hemophilia. This significant progress at the preclinical level,
      using both viral and non-viral vectors, paved the way for phase I clinical trials
      in patients suffering from hemophilia A. The first report on hemophilia A gene
      therapy using a non-viral ex vivo approach was encouraging and revealed modest
      improvements in clinical endpoints. The status of clinical gene therapy for the
      treatment of peripheral limb and myocardial ischemia by therapeutic angiogenesis
      was highlighted as showing an apparent increase in collateral development and
      reduced limb or myocardial ischemia in some patients. Gene therapy for cystic
      fibrosis turned out to be a much tougher nut to crack than initially assumed, and
      the hopes for, and hurdles faced by, gene therapy approaches for this disease
      were discussed. Phase III clinical trials using retroviral-based suicide gene
      therapy for cancer revealed no significant therapeutic benefit in patients
      suffering from glioblastoma multiforme. Nevertheless, new and promising
      approaches for cancer gene therapy are being developed that rely on the use of
      targetable vectors and conditionally replicating vectors that replicate
      specifically in cancer cells; this may overcome some of the bottlenecks of cancer
      gene therapy by improving therapeutic efficacy. Although few diseases have been
      treated effectively by gene therapy so far, the stage appears set for new and
      significant advances in clinical trials.

PMID- 15562328
TI  - Target molecules - design, optimization and production. The Knud Lind Larsen
      Symposium. 25-26 January 2002, Copenhagen, Denmark.
AB  - The Knud Lind Larsen Symposium, sponsored by the Danish Academy of Technical
      Sciences, was held on 25-26 January in Copenhagen, Denmark. A diverse line-up of
      lecturers presented research on target molecules, those molecules intended for
      particular applications such as binding to biological or synthetic receptors or
      as materials or catalysts. The symposium was well attended and highly
      interactive. Of interest to those involved in drug discovery were lectures on
      histone deacetylase inhibitors, which are being investigated as anticancer
      agents, second generation non-nucleoside reverse transcriptase inhibitors based
      on Sustiva (efavirenz), and a phage display approach to new insulin mimetics.

PMID- 15562329
TI  - Proteolytic enzymes as therapeutic targets - Keystone Symposium. 3-8 February
      2002, Keystone, CO, USA.
AB  - The Keystone Symposium 'Proteolytic Enzymes as Therapeutic Targets' was attended
      by approximately 150 scientists. Around two-thirds of the participants consisted
      of representatives from pharmaceutical companies, but representatives from
      academic institutes dominated the list of speakers. The meeting attracted
      scientists from many different fields, including biochemistry, molecular biology,
      structural biology, pharmacology, chemistry, and bioinformatics. The science
      ranged from the discovery and characterization of novel proteinases to the
      development and clinical trials of proteinase inhibitors and was presented as
      posters or in oral sessions. The discussions following the oral presentations
      were always very animated, but hardly ever heated. Although there were a few new
      drugs being presented, the real highlight was the enormous potential of recently
      discovered proteinases as new therapeutic targets. Both pharmaceutical companies
      and academic institutes are investing in programs to integrate the avalanche of
      new information coming from functional genomics, proteomics and structural
      information to create a platform for applied proteinase technology.

PMID- 15562330
TI  - Proteolytic Enzymes as Therapeutic Targets - Keystone Symposium. Targeting ICE
      and ACE. 3-8 February 2002, Keystone, CA, USA.
AB  - The meeting covered a diverse range of topics, from therapeutic design of
      inhibitors of human proteases involved in disease, to the discovery of novel
      protease targets in infectious organisms. Various techniques were described,
      including the bioinformatics-based scanning of genomes for novel enzymes that
      might be linked to disease or virulence. In addition, crystal structures of well
      known proteases were presented. The key focus however, was on designing
      inhibitors of proteolytic enzymes and their use in controlling disease processes
      mediated by proteases. Inhibitors described ranged from naturally occurring novel
      peptides such as Ascaris pepsin inhibitor, to trials with finely tuned
      peptidomimetics inhibiting human peptidases (interleukin converting enzyme; ICE
      and angiotensin converting enzyme; ACE) and rhinovirus 3C protease
      (antirhinovirus therapeutics; Pfizer Inc). The meeting also included
      presentations on the development of new techniques for detecting and analyzing
      protease activities such as luminescent protease assays, in vivo imaging of
      protease activity, surface plasmon resonance and novel peptide library screening
      methods.

PMID- 15562332
TI  - Anti-cancer treatment - 12th International Congress. Third Interactive
      Gastrointestinal Oncology Meeting. 4-7 February 2002, Paris, France.

PMID- 15562331
TI  - Anti-cancer treatment - 12th International Congress. 4-7 February 2002, Paris,
      France.
AB  - The 12th International Congress on Anti-Cancer Treatment (ICACT), endorsed by the
      American Society of Clinical Oncology, was held in Paris, France. Led by Gabriel
      Hortbagyi (MD Anderson Cancer Center, USA) and David Khayat (Hopital de la Pitie
      Salpetriere, France), the meeting was well organized and attended by several
      thousand participants from many countries. The list of members forming the
      Scientific Committee included well-known international experts whose involvement
      was reflected in the scientific excellence of the presentations.

PMID- 15562333
TI  - Membrane Channels: pores for Thought? - SCI Conference. 5 February 2002, London,
      UK.

PMID- 15562334
TI  - Rethinking the pathogenesis of asthma - Keystone Symposium. 8-13 February 2002,
      Santa Fe, NM, USA.
AB  - This Keystone meeting entitled 'Rethinking the Pathogenesis of Asthma' was held
      at Santa Fe, USA. Numerous topics were discussed, including the pathogenesis of
      asthma, from the perspective of better understanding the contribution of the
      immune system and the impact of environmental factors on the development of
      allergic diseases, and current research and new trends in immunotherapy to
      prevent and treat asthma. Of particular relevance to novel drug development was a
      session entitled 'Novel therapeutic approaches' co-chaired by Achsah D Keegan
      (American Red Cross, USA) and Arthur M Krieg (Coley Pharmaceutical Group, USA),
      in which the results of several clinical trial studies on potential new asthma
      therapies were presented.

PMID- 15562335
TI  - Proteomics and the Proteome - IBC's Fifth Annual Conference. 18-20 February,
      Geneva, Switzerland.
AB  - The complexity of humans lies in their proteins, not genes. Although a number of
      technologies are currently employed to analyze protein complexity, no single
      proteomics technology is adequate. Varying concentrations and wide dynamic range
      are among the major challenges in protein analyses. On average, each protein has
      the ability to exist in more than five different forms in a cell, thus, novel
      concepts in target discovery that are compliant with this 'isoform world' require
      development.

PMID- 15562336
TI  - Treatment for diabetic nephropathy - a review of the recent patent literature.
AB  - Diabetic nephropathy is now the leading cause of end-stage renal disease in the
      Western world. Renal disease develops secondary to long-standing hyperglycemia
      and hemodynamic alterations, which activate a common pathway that ultimately
      leads to the renal damage. Current strategies to treat diabetic nephropathy
      include optimization of glycemic control and treatment of glomerular and systemic
      hypertension. Although these strategies can slow the progression of proteinuria
      and decline in renal function, diabetic nephropathy remains a huge clinical
      problem. It is anticipated that future treatment modalities for preventing and
      treating diabetic nephropathy will involve drugs that modulate common
      pathogenetic pathways, possibly acting to inhibit both metabolic and
      hemodynamically induced forms of renal injury. These include inhibitors of growth
      factor and cytokine release or action, and inhibitors of intracellular second
      messengers. Although most of these agents have only been investigated in vitro,
      in animal experiments, or in relatively short-term human studies, these studies
      suggest that therapeutic strategies which involve a multifactorial approach may
      be more successful in the treatment of diabetic kidney disease than drugs which
      influence only one pathway.

PMID- 15562337
TI  - HMG-CoA reductase inhibitors - a review of the recent patent literature.
AB  - Statins are very potent inhibitors of HMG-CoA reductase, the rate-limiting enzyme
      in cholesterol biosynthesis at the mevalonate level. Today there is an increasing
      tendency to treat hypercholesterolemia aggressively, hence, the greater use of
      statins worldwide. The pleiotropic effect of statins is well documented.
      Examination of the patent literature reveals that in the past year pharmaceutical
      companies continued to be very active in this area. Accumulated knowledge of the
      actions of statins shows that they may be involved in many more processes than
      originally anticipated. Hence, in addition to 'old' indications
      (hypercholesterolemia, hyperlipidemia and atherosclerosis) many patent
      applications published in 2001 attempted to cover combination therapies, widening
      indications for statins to almost all known diseases. Many of the 'new' claims
      are not well substantiated and biological data are absent. Based on the magnitude
      of cardiovascular disease and aging population globally this area of drug
      discovery will continue to be an important area of research for all
      pharmaceutical companies.

PMID- 15562338
TI  - Indisetron Kyorin.
AB  - Indisetron is a 5-HT(3)/5-HT(4)antagonist under development by Nisshin Flour
      Milling and Kyorin as a potential treatment for emesis [158420], [248538]. By
      January 2000, phase III trials had commenced for this indication [352077].

PMID- 15562339
TI  - Propiram Shire.
AB  - Shire is developing propiram (Dirame, under license from Bayer), a non-addictive
      analgesic for the relief of moderate-to-severe pain. It is intended for the
      management of cancer pain, traumatic and post-surgical pain, and pain associated
      with dental surgery and childbirth [201830]. Propiram is effective for the
      treatment of mild-to-moderate pain and is more active than codeine, while showing
      no addictive potential. In July 2001, Shire confirmed that the product was
      undergoing phase III trials and anticipated launch in its first market to take
      place in 2003 [317541], [415823]. In June 2001, ABN AMRO predicted launch in 2003
      with sales of $16 million in 2003 rising to $24 million in 2005 [422762].

PMID- 15562340
TI  - [Does co-operation research provide approaches to explain the changes in the
      German hospital market?].
AB  - The German hospital market faces an extensive process of consolidation. In this
      change hospitals consider cooperation as one possibility to improve
      competitiveness. AIM: To investigate explanations of changes in the German
      hospital market by theoretical approaches of cooperation research. METHOD: The
      aims and mechanism of the theories, their relevance in terms of contents and
      their potential for empirical tests were used as criteria to assess the
      approaches, with current and future trends in the German hospital market
      providing the framework. Based on literature review, six theoretical approaches
      were investigated: industrial organization, transaction cost theory, game theory,
      resource dependency, institutional theory, and co-operative investment and
      finance theory. In addition, the data needed to empirically test the theories
      were specified. RESULTS: As a general problem, some of the theoretical approaches
      set a perfect market as a precondition. This precondition is not met by the
      heavily regulated German hospital market. Given the current regulations and the
      assessment criteria, industrial organization as well as resource-dependency and
      institutional theory approaches showed the highest potential to explain various
      aspects of the changes in the hospital market. CONCLUSION: So far, none of the
      approaches investigated provides a comprehensive and empirically tested
      explanation of the changes in the German hospital market. However, some of the
      approaches provide a theoretical background for part of the changes. As this
      dynamic market is economically of high significance, there is a need for further
      development and empirical testing of relevant theoretical approaches.

PMID- 15562341
TI  - [Me-too pharmaceuticals -- marketing-strategies of drug producers and drug
      purchasers. Example: non-ionic contrast media].
AB  - In the context of increasing economic pressure upon on hospital budgets, it is
      inevitable that central and standardized purchasing of pharmaceuticals must be
      considered. It was the aim of this assessment to analyse the many different non
      ionic contrast media/CM products on the actual "clinical relevance of the
      differences" in order to give advice for a more concerted purchasing of CM. The
      assessment was commissioned by a large scale Austrian hospital cooperation; it
      can be regarded as the beginning of a broad strategy against the many new, only
      rarely innovative, but nevertheless patent-protected pharmaceuticals. Eight
      different non-ionic contrast media - used in routine care - were compared for
      their physico-chemical characteristics: osmolality, nephrotoxicity, viscosity,
      hydrophilicity and electric charge. In a systematic review 193 publications were
      analysed. RESULT: The examined CM show similar pharmacokinetic and -dynamic
      attributes, and no differences of clinical relevance. An optimisation of
      purchasing pharmaceuticals by standardisation of the range of products takes
      place in the context of common strategies of producers and buying agents in
      marketing-economies. The strategies of the pharmaceutical industry (patent
      protection of me-too drugs, high-price-policy, extensive marketing of up to 40 %
      of revenue) and the counter-strategies of the central hospital purchasers (market
      concentration, drug commissions, institutional measures to disentangle interests)
      are presented - exemplified by contrast media - in this article.

PMID- 15562342
TI  - [A validated questionnaire for measuring patient satisfaction in general and
      specialist ambulatory medical care: the Qualiskope-A].
AB  - PURPOSE: To develop a reliable and valid questionnaire to measure patient
      satisfaction in ambulatory care, enabling a detailed analysis of the determinants
      of patient satisfaction that is applicable in GP and specialist outpatient care.
      DESIGN: Questionnaire with 27 single items subdivided into four categories:
      "professional competence", "physician-patient interaction", "information", and
      "practice organisation". Survey of 3,487 patients in 123 medical practices. 1,151
      patients were in specialist care and 2,336 patients in general medical care.
      RESULTS: Qualiskope-A is a reliable and valid instrument for measuring patient
      satisfaction in ambulatory care. All item-total correlations for single items
      were greater than r = 0.40. Coefficients for Cronbach's alpha for the four
      dimensions ranged between 0.87 and 0.94. CONCLUSIONS: The increasing political
      importance of patients' attitudes and satisfaction for the development of policy
      measures to ensure and improve the quality of care is beyond doubt. To make sure
      that the measurement of patient satisfaction does not only serve to meet
      regulatory requirements but helps to improve the quality of care and provides
      reliable data for health services research, a high standard is required for the
      questionnaires to be used. The Qualiskope-A and only few other instruments meet
      this high standard.

PMID- 15562343
TI  - [Preventive home visits to the elderly: systematic review of available evidence].
AB  - The aim of preventive home visits to elderly persons is to reduce mortality, to
      avoid admissions to nursing homes and hospitals and to improve the functional
      status and general wellbeing of the elderly. Preventive home visits are rarely a
      standard service in national health care systems. For over 20 years, controlled
      randomized studies have been carried out to test their effectiveness. This
      systematic review evaluates the evidence available on preventive home visits for
      elderly persons in the context of considerations relating to the incorporation of
      such a service into the German health care system. Three current systematic
      reviews (two of them meta-analyses) were identified in a systematic literature
      survey. They consider a total of 26 studies, most of them RCTs. A further three
      original controlled studies were identified and evaluated. The original studies
      were very heterogeneous with respect to goals, target groups, intensity and
      duration of the home visit programme and with respect to the individuals
      performing the study (number, profession, qualifications and cooperation). This
      makes it more difficult to perform a pooled overall evaluation. It was possible
      to consider mortality, admissions to nursing homes, functional status and
      psychosocial status as relevant target parameters. The systematic reviews arrive
      at different assessments of effectiveness. A quantitative, across-studies
      evaluation demonstrated that preventive home visits to elderly persons were
      effective both in studies with selected and with unselected inclusion of
      participants. The second meta-analysis did not confirm this result. Effectiveness
      here was only demonstrated using stratified analyses which investigated a large
      number of home visits, the performance of a multidimensional assessment with
      follow-up visits and the average age and morbidity of participants as relevant
      influencing factors. However no factor exerted an influence over more than one of
      the investigated target parameters. The findings thus constitute very unspecific
      evidence of effectiveness with largely unclear determinants of success.
      Preventive home visit programmes have been tested in various health systems.
      Results from controlled (randomised) German studies have not been published to
      date. The results of studies from other countries have only limited applicability
      to the conditions in the German health care system because the opportunities for,
      and extent of, economical and effective improvement in the preventive care of the
      elderly depend on the standard of care existing in the individual country. The
      additional value of screening depends on the empirical level of care and not on a
      given standard. At present the introduction of home visits in Germany cannot be
      recommended beyond studies. However there appear to be sufficient reasons for
      controlled studies in Germany which should be carried out in a coordinated way
      with mutual agreement on concepts.

PMID- 15562344
TI  - [Aspects of the legal concession and its procedures concerning the commitment of
      juveniles to safe custody institutions in youth welfare care according to German
      (section sign) 1631 b BGB -- an Inquiry into 101 cases of adolescent psychiatric
      expertise].
AB  - OBJECTIVES: Legal procedures concerning the legal concession of juveniles to safe
      custody care in youth welfare according to German section sign 1631 b BGB were to
      be examined. METHOD: 101 cases of adolescent psychiatric expertise were
      retrospectively examined. RESULTS: Legal procedures were unsatisfactory. A
      guardian ("Verfahrenspfleger" according to German law) was usually not named
      (79.2 %), especially not in cases of juveniles under 14 years of age (94 %) who
      cannot take part in the procedure on their own right, and not in cases of
      foreigners (89 %). In a number of cases the adolescence psychiatrist did not
      agree with statement of the youth welfare office regarding the juvenile
      confinement. In cases where the expert's counsel was a "process diagnosis"
      evaluating the juvenile's concrete ability to cooperate and to accept alternative
      forms of placement, closed commitment could be reduced significantly. Experts did
      not precisely term of commitment in a number of cases (15.9 %). CONCLUSIONS:
      Legal procedures concerning the legal commitment of juveniles to safe custody
      care in youth welfare institutions are partly unsatisfactory, especially
      according to the juvenile's rights regarding the legal procedure and the ways,
      how these rights are safeguarded.

PMID- 15562345
TI  - [Quality indicators for ambulatory health education programme for overweight and
      obese children and adolescents].
AB  - BACKGROUND: In Germany, 9 to 12 % of all children between five and seven years of
      age have been shown to be overweight at school entry; 2.5 to 3.5 % of them are
      obese. Therapeutic intervention for obese children and adolescents is considered
      to be indicated especially in cases where an increased body mass index (BMI) is
      accompanied by a disease the effective treatment of which requires weight loss.
      Furthermore, the child and its family must be willing to actively change their
      habits. OBJECTIVE: A multitude of health care providers have begun to offer
      multidisciplinary group programme for prevention and treatment of obesity to
      affected individuals and their families. The Medical Service of the Statutory
      Health Insurance (MDK) has therefore developed a list of quality and assessment
      criteria for such programme. METHODS: A systematic search for information in
      international and national publications was performed using standard methodology
      of evidence-based medicine. Data were extracted and assessed according to pre
      defined criteria taking into consideration previously published clinical
      guidelines and opinions of expert panels. RESULTS: Nearly all available studies
      were of low internal validity and mostly of poor methodological quality.
      Therefore, no binding recommendations for the design of health education
      programme for overweight and obese children and adolescents can be given.
      Potentially successful intervention should combine the following 4 modules:
      nutrition, physical activity, change of eating habits, physical activity habits
      and life style using methods of behavioural therapy, and involvement of parents.
      Such combinations may have the potential to reduce or stabilise the BMI at least
      during a defined period of time. In younger children, the beneficial effect will
      be more pronounced if the parents are actively involved. CONCLUSION: Up to now
      informative studies have not reliably shown that the effect of ambulatory health
      education programmes for overweight and obese children and adolescents and their
      parents may last for more than one or two years. Therefore, a controlled clinical
      trial determining the long-term effectiveness of such programme is imperative.
      The decision whether a defined programmes should be included in such a study
      could be taken on the basis of the quality indicators and assessment criteria
      described here.

PMID- 15562346
TI  - [Prevalence of caries, fissure sealants and filling materials among German
      children and children of migrants].
AB  - The aim of this study was to collect information on dental health and dental care
      of German children and children of migrants for planning oral health promotion in
      the Rems-Murr-district. To meet this aim all first and fourth degree children in
      primary and special schools were examined. The dmft- and DMFT-Index, the number
      of fissure sealants, the filling material used and the children's nationality
      were recorded. The dmft of 6- and 7-year-olds was 1.50 among Germans, 4.61 among
      German migrants from Russia, 4.02 among Turks, 4.05 among children from former
      Yugoslavia, 2.35 among Italians, 1.95 among Greeks and 3.76 among children of
      other nationalities. At the age of 9 to 10 years Germans had an average of 0.31,
      German migrants from Russia 0.77, Turks 1.19, children from former Yugoslavia
      1.32, Italians 0.64, Greeks 0.69 and children of other nationalities 0.57 DMF
      teeth. In both age groups the proportion of caries-free children was highest
      among Germans and lowest among Turks. Also, more migrants than Germans were
      referred to a dentist for caries treatment. Compared to the Germans fewer
      migrants had at least one tooth sealed. The proportion of amalgam fillings to the
      total number of fillings was higher among 9- and 10-year-olds of Turkish, Italian
      or Yugoslavian origin than among other nationalities. The results of this study
      show that further development of oral health promotion programmes for children
      and parents with Turkish and Russian cultural background has the top-most
      priority.

PMID- 15562347
TI  - [Secondary individual prevention and rehabilitation in female hairdressers
      suffering from skin diseases].
AB  - The risk of contracting occupational skin diseases is highest in hairdressers. A
      job-specific secondary prevention programme was created to enable hairdressers to
      stay on the job despite their skin problems. The effect of this prevention
      programme on both, the severity of skin disorders and the hairdressers' behaviour
      regarding skin protection are evaluated in this paper. Between 1997 and 2002 a
      total of 2437 hairdressers participated in the programme. Complete data for the
      evaluation are available for 635 hairdressers (26 %). This selection is partly
      due to the fact that the evaluation is restricted to certain regions in Germany.
      The percentage of hairdressers with severe skin symptoms dropped from 49 % at the
      start of the rehabilitation programme to 11 % after completion of the programme.
      The proportion of hairdressers using gloves and applying skin care doubled.
      Therefore the rehabilitation programme appears to be successful regarding the
      ability of hairdressers to cope with skin problems.

PMID- 15562348
TI  - ["Loss of perspective is my disease" -- subjective feelings of long-term
      unemployed].
AB  - BACKGROUND: Nowadays job loss implies the risk of long-term unemployment
      particularly in former East Germany. Many physical, psychological and social
      problems are associated with unemployment. However, health of long-term
      unemployed may not decrease continually, but may be subject to fluctuations
      according to different phases of unemployment and short-term work. METHODS: This
      expectation was examined by structured interviews with long-term unemployed (10
      men and women) working in temporary job-creating-schemes (ABM). We asked for
      determinants of health and subjectively perceived associations between health and
      employment as well as for conditions of life and work. RESULTS: The employees
      were on average 55 years old and more than 7 years without work before joining
      the ABM. Psychosocial complaints such as depression, sleep disorders or
      nervousness appeared after approximately three months of unemployment. Subjective
      health improved during job-creating-schemes, depending on specific work
      conditions, but deteriorate at its end again. Most of the ABM-employees don't
      have any perspective of future employment. CONCLUSIONS: The well-known
      association between unemployment and health was confirmed. Furthermore, the study
      gave new insights into psychological strains of long-term unemployed and
      subjective work loads during ABM. Future prospects were proved to be an important
      determinant of health ('lack of perspective is my illness'). From this measures
      of health promotion for long-term unemployed within ABM companies and other
      institutions can be derived.

PMID- 15562349
TI  - [Diseases of the orbit--the role of the ophthalmologist as network coordinator].

PMID- 15562350
TI  - [Diseases of the orbit--an interdisciplinary challenge!].

PMID- 15562351
TI  - [The methodology and accuracy of MRI-based orbital volume calculations].
AB  - OBJECTIVE: The aim of the present work was to establish a method for orbital
      volume calculation based on MR scanning data for the sake of better radiation
      hygiene. MATERIALS AND METHODS: The orbital volumes of 35 ophthalmologically
      healthy children were calculated on the basis of MRI scans. After data transfer
      to a separate workstation, volumetric analysis was carried out by two independent
      radiologists using semi-automated software. The accuracy of the calculated values
      was compared with orbital volumes measured by anatomic preparations and given in
      studies by various authors. RESULTS: Volume calculation was possible in all
      patients using MRI data. There is an acceptable agreement with the presented
      anatomic facts and the measured values of Bentheley. In the Wilcoxon test there
      was not a big difference between the courses of the values (p = 0.507).
      CONCLUSION: Even though we can obtain a better image of the bizarre structure of
      the bony orbits with CT, MR-based volumetry of the orbit is a reliable method and
      is not burdened by radiation exposure. It can thus be an important condition for
      the planning and the controlling of modern therapeutic concepts in treating
      anophthalmos and microphthalmos.

PMID- 15562352
TI  - [Orbital volume in congenital clinical anophthalmos].
AB  - INTRODUCTION: The purpose of this study is to report orbital volume measurement
      results in patients with congenital clinical anophthalmia before and after
      therapy and to compare them with normal values. PATIENTS AND METHOD: Normal
      values were obtained from 35 healthy children (22 boys, 13 girls; aged 3 month to
      7 years) in whom MRI was done for non-ophthalmological reasons. 18 patients with
      congenital anophthalmos could be included, 9 with bilateral, 8 with unilateral
      disease and 1 microphthalmos. 6 of them had MRI follow-up (more than one
      examination). RESULTS: Orbital volume at birth is 7 ml and it increases with age:
      Orbital volume = 7.701 x age (month) (0.2484) ml. It is around 14.2 ml at the age
      1 year, 17 ml with 2 years and reaches 23 ml with 7 years. In unilateral clinical
      anophthalmos orbital volume is 35 to 58 % compared with the healthy side and 31
      to 65 % compared with the normal values. In bilateral cases the volume is 43 to
      70 % of the normal value. During treatment it develops in parallel to the normal
      values. CONCLUSIONS: The normal values measured by our group are in accordance
      with the only published study by Bentley . MRI orbital volumetry is a reliable
      method without using radiation. It allows us to quantify the bony asymmetry and
      is suitable for therapy control when using orbital expanders. The congenital
      missing eye might be the most important reason why the orbit does not develop in
      the normal way to a normal size. Self-inflating high, hydrophilic hydrogel
      expanders do not seem to be able to compensate this, in spite of the fact that
      they work very well to prepare the socket for a prosthesis.

PMID- 15562353
TI  - [Treatment of carotid cavernous fistulas].
AB  - The diagnosis and treatment of carotid cavernous fistulas (CCF) is an
      interdisciplinary challenge for both ophthalmologists and interventional
      neuroradiologists. According to the clinical signs and symptoms the tentative
      diagnosis is made by the ophthalmologist. It is the task of the neuroradiologist
      to ascertain this diagnosis by intra-arterial angiography. If a fistula is
      suspected this invasive diagnostic procedure is indispensable, not only to
      establish the diagnosis but also to classify those types of fistula with an
      unfavourable spontaneous course possibly resulting in intracranial haemorrhage.
      The indication for therapy is based on the clinical symptoms and the angiographic
      findings. In a number of cases no therapy is required. Since a fistula may change
      over time, these patients have to be under close ophthalmological surveillance.
      In many patients a conservative therapeutic approach with manual compression of
      the carotid artery is sufficient as a fIrst step. Invasive treatment is performed
      via the endovascular approach in almost all cases. Direct CCF are predominantly
      treated transarterially with detachable balloons and/or coils. Recently,
      intracranial stents have been used increasingly. The embolisation of indirect CCF
      is most effective using the transvenous access with coils. There are several
      approaches to the cavernous sinus. The interventional occlusion of CCF is
      nowadays a very effective treatment associated with a comparatively high cure
      rate and low incidence of complications. By close cooperation between
      ophthalmologists and neuroradiologists the patients can be protected against
      visual loss, the development of a secondary glaucoma, and, most importantly,
      against intracranial haemorrhage.

PMID- 15562354
TI  - [Radiotherapy for Graves' ophthalmopathy].
AB  - Graves' ophthalmopathy (GO) is the most frequent extrathyroidal manifestation of
      Graves' disease, an autoimmune disorder of the thyroid, whereas the precise
      pathogenesis still remains unclear. In Hashimoto's thyroiditis the occurrence of
      proptosis is an extremely rare event. The therapy for middle and severe courses
      of GO shows in partly disappointing results, although several therapy modalities
      are possible (glucocorticoid therapy, radiotherapy, antithyroid drug treatment,
      surgery). All these therapies lead in only 40 - 70 % to an improvement of the
      pathogenic symptoms. An intensive interdisciplinary cooperation is necessary to
      satisfy the requirements for the treatment of Graves' ophthalmopathy. As a
      consequence of the very different results of the few of clinical studies that
      were accomplished with reference to this topic, treatment by radiotherapy in the
      management of the disease is presently controversially discussed. In the German
      speaking countries the radiotherapy is, however, firmly established as a therapy
      option in the treatment of the moderate disease classes (class 2-5 according to
      NO SPECS), especially if diplopia is present. This article describes the
      sequences, dosages and fractionation schemes as well as the risks and side
      effects of the radiotherapy. Altogether, radiotherapy is assessed as an effective
      and sure method. The administration of glucocorticoids can take place before the
      beginning of or during the radiotherapy. For the success of treatment the correct
      selection of patients who may possibly profit from a radiotherapy is absolutely
      essential. By realising that GO proceeds normally over a period of 2-5 years,
      which is followed by a period of fibrotic alteration, the application of the
      radiotherapy in the early, active phase is indispensable. A precise explanation
      for the effects of radiotherapy in treatment of the GO does not exist at present.
      The determination of the most effective irradiation doses was made from
      retrospectively evaluated collectives. Recently the results of a national survey
      of all German RT departments were published, initiated by the working group of
      the DEGRO (German Society of Radiooncology). In the most of the German
      radiooncology departments irradiation with 8 to 10 x 1.8-2.0 Gy 5 x weekly to 16
      or 20 Gy is standard. Two recently published prospective German studies pointed
      out the equivalence of the effectiveness of a short therapy in low dose ranges up
      to 2.4 Gy as well as of a low proportioned irradiation during a longer period in
      relation to a standard therapy with 20 Gy. That is why at the moment it is not
      possible to give a definite recommendation with reference to dosages or the
      fractionation schemes. In 2003 the first European group (European Group on Graves
      ' Orbitopathy Experience -- EUGOGO) was founded for pursuing investigations of GO
      in multi-centric studies, mainly to improve therapy results.

PMID- 15562355
TI  - [Orbital decompression in graves disease: indications, techniques, results and
      complications].
AB  - BACKGROUND: The surgical rehabilitation of patients with Graves disease involves
      orbital decompression and various lid and extraocular muscle procedures. METHODS:
      We have reviewed the literature and include a presentation of our own results.
      RESULTS: The indications for orbital decompression include not only functional
      reasons (optic neuropathy, keratopathy, glaucoma, pain) but also aesthetic and
      psychosocial reasons without visual problems. Current techniques for orbital
      decompression (bone versus fat removal) are described and discussed. Results
      demonstrating a mean reduction of proptosis (4 - 6 mm) and complications (mainly
      diplopia in 3 - 12 %) are presented for coronal and transconjunctival approaches
      and compared with other methods. CONCLUSION: Current techniques of orbital
      decompression are effective and safe and are therefore increasingly used not only
      for functional but also for aesthetic or "rehabilitative" indications.

PMID- 15562356
TI  - [Indications and surgical technique of the endonasal decompression of the optic
      nerve from an HNO medical viewpoint].
AB  - BACKGROUND: Acute and chronic progressive compression of the optic nerve is
      mostly caused by tumors and trauma. Special knowledge about the
      pathophysiological mechanisms of the nerve injury is necessary in all clinical
      disciplines managing optic nerve neuropathy. Hence, the technique, the
      indications and limitations of the endonasal endoscopic decompression procedure
      of the optic nerve will be described from an otolaryngological point of view.
      METHODS: On the basis of our own experience and the international literature, the
      indications and limitations of the endonasal-endoscopic approach for optic nerve
      decompression are described and critically reviewed. CONCLUSIONS: The management
      of optic nerve neuropathy, especially in cases of severe trauma, remains
      controversial. Because the data of the present clinical trials are mostly not
      evidence based, an efficient transfer of relevant guidelines or recommendations
      into the clinical practice is difficult. Therefore, the indication for optic
      nerve decompression surgery, especially in traumatic optic nerve neuropathy, must
      be individualized.

PMID- 15562357
TI  - [Treatment of eyelid retraction in Grave's disease by recession of the levator
      complex].
AB  - BACKGROUND: The chronic stage in Grave's orbitopathy is characterised by fibrotic
      changes within the orbital soft tissues, especially the extraocular muscles.
      Retraction of the eyelids is a common clinical feature of this phenomenon. To
      solve this problem several techniques for lengthening the upper eyelid have been
      described with variable rates of success. In this report we describe our modified
      Harvey's technique for the correction of upper eyelid retraction which includes a
      complete recession of the Muller's muscle/levator complex from the tarsal plate
      without the interposition of a spacer. Finally only the skin and the superficial
      orbicularis muscle are sutured. We also report about our results with this
      procedure. METHODS: 8 patients (1 male, 7 female) with lid retraction in Grave's
      ophthalmopathy were recorded who had undergone the modified lengthening technique
      by an external approach between 2001 and 2004. Four patients underwent a
      bilateral procedure and 1 patient showed a significant under-correction,
      necessitating reoperation. So a total of 13 procedures were included in this
      follow-up study. Beside the common ophthalmological examination, special interest
      was put in the difference of the two eyelid apertures in primary position pre-
      and postoperatively. RESULTS: Within a follow-up period of at least 3 months we
      recorded an averaged lengthening of the upper eyelid of 3.1 mm. The difference of
      the two eyelid apertures in primary position improved from 2.2 mm preoperatively
      to 1.0 mm postoperatively. Only 1 patient needed reoperation because of a
      significant under-correction. There were no late over-corrections observed.
      CONCLUSIONS: The modified Harvey's technique to lengthen the upper eyelid is a
      safe and effective method to reduce upper eyelid retraction in Grave's disease.
      An eventually required orbital decompression or extraocular muscle surgery has to
      be done before the lid surgery.

PMID- 15562358
TI  - [Strabismus surgery in Grave's disease--dose-effect relationships and functional
      results].
AB  - BACKGROUND: Strabismus in thyroid ophthalmopathy is based on a loss of the
      contractility and distensibility of the external ocular muscles. Different
      therapeutic approaches are available, such as recession after pre-. or
      intraoperative measurement, adjustable sutures, antagonist resection, or
      contralateral synergist faden-operation. PATIENTS AND METHODS: 26 patients with
      strabismus in thyroid ophthalmopathy were operated between 2000 and 2003. All
      patients were examined preoperatively, then 1 day and 3 - 6 months (maximum 36
      months) postoperatively. Before proceeding with surgery, we waited at least 6
      months after stabilization of ocular alignment and normalization of thyroid
      chemistry. RESULTS: Preoperative vertical deviation was 10-44 PD (mean 22), 3
      months postoperatively it was 2-10 PD (mean 1.5). Recession of the fibrotic
      muscle leads to reproducible results: 3.98 +/- 0.52 PD vertical deviation/mm for
      the inferior rectus. In the case of a large preoperative deviation a correction
      should be expected, which might not be sufficient in the first few days or weeks;
      a second operation should not be carried out before 3 months. 7 patients were
      operated twice, 1 patient need three operations. 4 patients (preop. 0) achieved
      no double vision at all; 15 patients (preop. 1) had no double vision in the
      primary and reading positions; 3 patients (preop. 0) had no double vision with a
      maximum of 5 PD; 1 patient (preop. 7) had double vision in the primary or reading
      position even with prisms; and 2 patients (preop. 17) had double vision in every
      position. CONCLUSIONS: We advocate that recession of the restricted inferior or
      internal rectus muscle is precise, safe and effective in patients with thyroid
      ophthalmopathy. The recessed muscle should be fixed directly at the sclera to
      avoid late over-correction through a slipped muscle. The success rate in terms of
      binocular single vision was 76 % and 88 % with prisms added.

PMID- 15562359
TI  - [Potentially fatal orbital disorder].
AB  - Fulminant processes of the orbit can cause considerable diagnostic difficulties
      with regards to the clinical, radiological and microbiological appearance. Rhino
      orbito-cerebral mucormycosis is a rare but, when untreated, fatal orbital disease
      capable of destructive infiltration of soft tissue and bone. It occurs preferably
      in the ill adjusted diabetic or in the course of an immunodeficiency. The
      following case report describes a leukaemia patient developing a severe rhino
      orbito-cerebral mucormycosis which was initially not recognised. Since untreated
      mucormycosis is fatal, an aggressive surgical approach with excision of the whole
      necrotic area is necessary even if the diagnosis cannot be confirmed with
      certainty.

PMID- 15562360
TI  - [Management of periorbital and orbital infections].
AB  - BACKGROUND: Infections of the orbit and of the periorbital region are not
      uncommon. Even today they constitute a serious problem, in spite of modern
      antibiotic treatment, with a potential risk of lethal complications. Orbital
      infections are most prevalent in children and adolescents. The acute orbit has
      many causes, but the most frequent is an occurrence secondary to acute
      rhinosinusitis. PATIENTS AND METHODS: Based on clinical cases, different causes
      and the present state of diagnosis are presented. The discussion deals with
      therapeutic strategies depending on the stage according to the current
      classification of orbital inflammation. CONCLUSIONS: Orbital and periorbital
      inflammations represent a demanding challenge for interdisciplinary cooperation
      between ophthalmologists, ENT specialists and radiologists. In some cases
      maxillofacial surgeons and neurosurgeons have to be included as well. Accurate
      diagnosis and treatment may lead to the resolution of the infection and avoid
      ocular sequel or endocranial complications as well as a fatal outcome.

PMID- 15562361
TI  - [Erdheim-Chester disease as differential diagnosis in bilateral exophthalmos].
AB  - This report describes the case of a patient who had symmetrical exophthalmos,
      periorbital xanthelasmas and reduced vision. Next to Wegener's granulomatosis the
      differential diagnosis of Erdheim-Chester disease is discussed. It concerns a
      rare systemic histiocytosis of unknown etiology. Above all, the skeleton system
      with symmetrical long bone osteosclerosis is affected. Manifestations in the area
      of the orbit have seldom been reported with bilateral retrobulbar infiltrations,
      exophthalmos, diplopia, compression of the optic nerve and periorbital
      xanthelasmas.

PMID- 15562362
TI  - [Orbital manifestation of microscopic polyangiitis (mPA)--presentation of
      clinical cases].
AB  - BACKGROUND: Microscopic polyangiitis (mPA) is one of the ANCA-associated primary
      systemic vasculitides. It is defined as necrotic vasculitis without granuloma
      development and without minimal immuno-depots in situ. The clinical picture is
      characterised by destruction of the small vessels with the main manifestations in
      the upper and lower respiratory tract, in the lungs and kidneys. The eye
      manifestations were noted yet not so often. PATIENT: There were 2 clinical cases,
      aged 5-12 years, with primary eye manifestations of the mPA. The initial oedema
      and the reddening of the lid area were common to all the patients. The diagnostic
      excisions of the inflammatory tumour of the anterior orbital area have shown
      histologically vasculitis of the small vessels. mPA was diagnosed by clinical and
      immunological parameters, including the examination of the respiratory tract and
      kidneys. CONCLUSIONS: In inflammatory orbital pseudotumour, diagnostic excision
      and evaluation of the immunological parameters are useful for the exclusion of a
      systemic vasculitis. Proper examinations must be performed to determine other
      possible organ manifestations. Prognosis is characterised by the severity of
      kidney involvement. Early immunosuppressive therapy is crucially important for
      survival prognosis.

PMID- 15562363
TI  - [Surgery of craniofacial deformities].
AB  - Most craniofacial abnormalities are craniosynostoses due to premature fusion of
      one or more craniofacial sutures. The typical cranial deformities result from
      growth inhibition perpendicular to the affected sutures. Functional impairment is
      caused either directly by the pathological growth pattern or indirectly by the
      increased intracranial pressure. Craniosynostosis is frequently accompanied by
      dysmorphia or dystopia of the orbits, resulting in possible functional problems.
      The indications for operation are to increase the intracranial volume and to
      correct aesthetic impairments. The planning of the surgical procedures has to
      consider the orbital problems. This review describes the different disease
      patterns of premature craniosynostosis and specific surgical approaches for their
      correction.

PMID- 15562364
TI  - [Experiences with a new plate-like implant system (Ti-Epiplating System) for
      rehabilitation of orbital and midfacial defects].
AB  - BACKGROUND: Since Tjellstrom introduced in 1977 percutaneous osseointegration,
      the importance of osseointegrated implants has increased in the head and neck
      region. Implants and craniofacial surgery technology have been permanently
      improved and the use of extraoral osseointegration has expanded considerably. The
      surgical reconstruction of the exenterated orbit provides often only poor
      aesthetic results. Therefore the rehabilitation of complex midfacial structures
      is an indication for osseointegrated retained facial prostheses. METHODS AND
      MATERIAL: The international literature has been reviewed concerning the topic of
      osseointegration for the retention of orbital and midfacial prostheses. A new
      plate-like implant system is introduced. We report about our experiences with the
      "Ti-Epiplating System". DISCUSSION: The "Ti-Epiplating System" is available since
      2001. For every location in the head and neck there exists a specially shaped
      plate. The "Ti-Epiplating System" is fixed subperiostally with normal bone
      screws, the same as used in traumatology. In cases of extended resections with
      less bone substance left, the application is simplified. The osseointegration
      time is reduced to a minimum of 6 weeks. Postoperative radiation is possible.
      CONCLUSION: The improved application of the "Ti-Epiplating System" is beneficial
      in the reconstruction of extended craniofacial defects with osseointegrated
      implants.

PMID- 15562365
TI  - [Materials used in reconstructive surgery of the orbit].
AB  - Orbital traumas and tumour operations may cause defects the operative management
      of which sets high requirements on the surgeon. For covering defects, transplants
      or implants are available. There is a risk of inflammation due to the free
      contact of the implants to the cavity of the inner nose or the sinus. Today,
      implants made from titanium, porous polyethylene, PDS (poly-p-dioxanon) foils,
      and ceramic materials are preferred. Alternatively, autogenous transplants can be
      used. These are immunologically harmless but they are of only limited
      availability. Moreover, a second operation for taking the transplants with
      creation of a donor defect is necessary.

PMID- 15562366
TI  - Cytotoxic T-lymphocyte responses to canarypox vector-based HIV vaccines in HIV
      seronegative individuals: a meta-analysis of published studies.
AB  - PURPOSE: A successful prophylactic HIV vaccine will probably require neutralizing
      antibodies and vigorous CTL (CD8+ T-cytotoxic lymphocyte) responses. Canarypox
      vector-based HIV vaccines (ALVAC-HIV) have been gaining momentum as promising HIV
      vaccine candidates because of their ability to elicit CTL responses. This
      quantitative meta-analysis was undertaken to determine a summary estimate of CTL
      responses to ALVAC-HIV vaccines in HIV-1 seronegative volunteers and to identify
      reasons for differences among studies in the estimated effects on CTL responses.
      METHOD: After a literature search and data abstraction, eight randomized, double
      blind, placebo-controlled studies were selected for meta-analysis. Stratified and
      random effects meta-regression analyses were performed to search for response
      differences among studies. RESULTS: Of the various study characteristics, the
      number of immunizations and the vaccine dose were associated with the likelihood
      of developing CTL responses. It was not possible to distinguish the effect of
      either the number of immunizations or the vaccine dose on CTL responses because
      these two study characteristics were highly associated with each other.
      CONCLUSION: More trials are warranted to determine the ideal dose/immunization
      schedule that would elicit maximal CTL responses.

PMID- 15562367
TI  - Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis.
AB  - PURPOSE: To evaluate the effects of alendronate, vitamin D, and calcium
      supplementation on bone metabolism and bone mineral density (BMD) in both HIV
      infected men and women treated with highly active antiretroviral therapy (HAART).
      METHOD: We performed a 52-week prospective, multicenter, randomized, open-label
      clinical trial. Eligible participants were on stable HAART and had BMD values at
      the femoral neck or lumbar spine that corresponded to a t score less than -1.
      Patients were randomized to receive alendronate 70 mg weekly or no alendronate;
      calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study
      recipients. Primary endpoint of the study was the change in bone metabolism
      evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline
      phosphatase; the secondary endpoint was BMD variation. RESULTS: 18 patients were
      randomized to the alendronate and 23 to the no-alendronate group (controls). The
      alendronate-treatment group compared to controls had a significant decrease in
      serum N-telopeptides, 1914 +/- 1433.4 vs. 3967 +/- 1650.5 pM/L (p = .005) after 1
      year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs.
      3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD
      decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control
      group (p = .04). No between-groups differences for BMD were found (Delta lumbar
      BMD 0.0351 +/- 0.0406 in cases and 0.0356 +/- 0.073 in controls [p = .977], Delta
      femoral-BMD -0.085 +/- 0.160 in cases and -0.100 +/- 0.165 in controls [p =
      .795]). CONCLUSION: Alendronate plus vitamin D and calcium was effective in
      reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral
      BMD decrease after 52 weeks compared to treatment with vitamin D and calcium
      alone in patients on HAART with osteopenia/osteoporosis.

PMID- 15562368
TI  - Higher rates of viral suppression with nonnucleoside reverse transcriptase
      inhibitors compared to single protease inhibitors are not explained by better
      adherence.
AB  - BACKGROUND: Although evidence suggests that antiretroviral (ARV) regimens
      containing nonnucleoside reverse transcriptase inhibitors (NNRTIs) are superior
      to single-protease inhibitor (PI)-based regimens at suppressing viral load, it is
      unclear how much of the improved viral suppression is due to intrinsic drug
      potency versus higher levels of adherence to simpler regimens. We therefore
      examined adherence and viral suppression in NNRTI and single-PI regimens in a
      cohort of largely ARV-experienced participants by using objective measures of
      adherence. METHOD: Participants were recruited from the Research on Access to
      Care in the Homeless (REACH) Cohort and were included in the study if they were
      on single-PI-based or NNRTI-based highly active antiretroviral therapy (HAART)
      regimens for at least 3 months prior to study entry. Adherence was measured by
      unannounced pill counts at the participant's usual place of residence. The
      primary outcome was suppression of HIV viral RNA to <50 copies/mL. RESULTS: Among
      109 individuals who were followed for a median of 8.7 months, the odds of
      virologic suppression were approximately 8 times higher (p < .01) for
      participants on NNRTI-based regimens (n = 53) compared with those using single-PI
      based regimens (n = 56) when controlling for adherence, as well as other
      potential confounders in a multivariable analysis. The only other independent
      predictors of viral suppression in multivariable modeling were ARV adherence (p <
      .01), CD4 nadir (p = .02), and continuous months on current regimen prior to the
      start of adherence monitoring (p < .01). There was no significant difference in
      adherence by unannounced pill counts in participants receiving NNRTI- versus
      single-PI-containing regimens. CONCLUSION: A higher proportion of individuals
      using NNRTI-based regimens had viral suppression when compared to those taking
      single-PI-containing regimens, and this association was not confounded by higher
      levels of adherence. These results suggest that improved viral suppression on
      NNRTI regimens compared to single-PI regimens is more closely associated with
      regimen potency than higher levels of adherence.

PMID- 15562369
TI  - Pharmacokinetics of antiretrovirals administered to HIV-infected children via
      gastrostomy tube.
AB  - BACKGROUND: Surgical placement of a gastrostomy tube (g-tube) directly into a
      patient's gastrointestinal system to support antiretroviral administration is
      occasionally used to increase adherence in HIV-infected children. Absorption and
      distribution characteristics of antiretrovirals after g-tube administration,
      however, are unknown. The goal of this pilot study was to describe the
      pharmacokinetic characteristics of protease inhibitors (PIs) and nonnucleoside
      reverse transcriptase inhibitors (NNRTIs) when administered to HIV-infected
      children via g-tube. METHOD: Nine HIV-infected children who were receiving a PI-
      or NNRTI-containing regimen via g-tube were enrolled. All antiretrovirals
      (excluding efavirenz) were administered under direct observation for the
      pharmacokinetic evaluation. Blood samples were collected at predose and at 1, 2,
      4, 8, and 12 hours postdose. Antiretroviral concentrations were measured in
      plasma using high performance liquid chromatography with ultraviolet detection.
      RESULTS: Systemic exposure of PIs and NNRTIs in our 9 patients was similar to
      data from historical oral administration controls. Due to likely drug
      interactions, LPV exposure was decreased and one patient had low exposure of all
      antiretrovirals. When doses were increased, adequate exposure was attained.
      CONCLUSION: This pilot study suggests that administration of most PIs and NNRTIs
      by a g-tube to HIV-infected children provides systemic exposure comparable with
      that achieved after oral administration.

PMID- 15562370
TI  - Cost-effectiveness of lopinavir/ritonavir versus nelfinavir as the first-line
      highly active antiretroviral therapy regimen for HIV infection.
AB  - PURPOSE: Selecting the optimal treatment regimen for antiviral-naive patients may
      be difficult, given the concern about the antiviral activity, the development of
      drug resistance, and the increase in drug costs. This study evaluates the costs
      and effectiveness of using lopinavir/ritonavir (LPV/r) vs. nelfinavir (NFV), both
      coadministered with stavudine and lamivudine, as the first HAART regimen in
      treating HIV patients, based on the results from the published clinical trial M98
      863. METHOD: A Markov model was developed using a combination of viral load (VL)
      and CD4 count as surrogate markers to define health states. VL and CD4 count data
      from the 48-week analysis of the clinical trial were used as measures of effect.
      The impact of resistance difference between NFV and LPV/r was also examined.
      RESULTS: Over the first 5 years, the model estimated that LPV/r could save $3,461
      USD per patient in total HIV care costs compared with NFV. If the resistance
      advantage of LPV/r was taken into account, the cost savings by LPV/r increased to
      $5,546 USD. For longer term projection, without considering the resistance
      difference, the incremental cost-effectiveness ratio (CER) for LPV/r vs. NFV was
      $6,653 USD per quality-adjusted life-year (QALY). This CER compares favorably to
      therapies for HIV disease and for common drug treatments for other conditions and
      is well within accepted thresholds for health policy makers. CONCLUSION: When
      treatment options are being considered, this study suggests that use of LPV/r in
      the first antiretroviral regimen, as compared to NFV, is cost-effective based on
      improved efficacy and resistance.

PMID- 15562371
TI  - Highlights from the 13th International Symposium on HIV and Emerging Infectious
      Diseases (ISHEID).

PMID- 15562372
TI  - Oral presentation abstracts from the 13th International Symposium on HIV and
      Emerging Infectious Diseases (ISHEID). June 3-5, 2004. Toulon, France.

PMID- 15562373
TI  - Circulating levels of IL-7 but not IL-15, IGF-1, and TGF-beta are elevated during
      primary HIV-1 infection.

PMID- 15562374
TI  - Homocysteine, glycine betaine, and N,N-dimethylglycine in patients attending a
      lipid clinic.
AB  - We recruited nondiabetic subjects (n = 158) attending a lipid disorders clinic, a
      subset of whom (n = 46) had established cardiovascular disease. Glycine betaine,
      N,N-dimethylglycine, and carnitine were measured in fasting plasma and urine
      samples. The concentrations and excretions were related to known cardiovascular
      risk factors in multivariate regression models. The relationships between
      homocysteine and plasma and urinary glycine betaine were highly significant (P <
      .002), comparable with the known relationships with folate and plasma creatinine.
      The regression coefficient for plasma glycine betaine was consistently
      approximately -0.1 in 5 different regression models (3 best-subsets and forward
      and backward stepwise regression models) for predicting homocysteine using 23
      variables. Plasma glycine betaine was higher in males than in females, and the
      difference was associated with a difference in percentage of body fat. Its
      concentration included a constant factor of approximately 20 micromol/L that was
      independent of any of the variables investigated here. In the total group, body
      fat, homocysteine, and carnitine were significant predictors of plasma glycine
      betaine. Carnitine, an important betaine that is involved in lipid metabolism
      positively correlated with both homocysteine and glycine betaine. In our sample,
      the urinary excretion of glycine betaine was outside the reference range in 14 of
      the 158 subjects and the betaine fractional clearances were above the reference
      range in 23 subjects. Fractional clearance correlated strongly with plasma
      homocysteine (r = 0.50), and this relationship may be stronger in patients with
      known vascular disease. Urinary loss of glycine betaine may contribute to
      hyperhomocysteinemia and the development of cardiovascular disease.

PMID- 15562375
TI  - Human chorionic gonadotropin therapy in adolescent boys with constitutional
      delayed puberty vs those with beta-thalassemia major.
AB  - We studied 12 adolescent boys with beta-thalassemia major and delayed puberty
      (age, 15.8 +/- 1 years) with Tanner I sexual development treated with a long-term
      low-transfusion regimen. Ten nonthalassemic adolescents (> 14 years) with
      constitutional delay of growth and puberty (CDGP) served as controls. Auxologic
      parameters and testicular size were measured, and bone age was determined.
      Measurement of basal gonadotropin (luteinizing hormone [LH] and follicle
      stimulating hormone [FSH]) and testosterone (T) levels taken at 8 am revealed
      prepubertal levels in both groups of patients. Human chorionic gonadotropin (hCG,
      2500 U/m(2)) was injected intramuscularly twice weekly for 6 months, and
      anthropometric data, testicular diameter, and serum T concentrations were
      remeasured after 1 and 6 months. The testicular diameter after 6 month of hCG
      therapy was significantly correlated with the testicular diameter and T level
      after 1 month of therapy (r = 0.93 and 0.39, respectively, P < .01). After 6
      months of hCG therapy, the mean growth velocity (GV) increased from 4.1 to 8.6
      cm/y in thalassemic patients and from 4.6 to 10.3 cm/y in those with CDGP during
      hCG therapy. In thalassemic boys, the mean T concentration increased from 0.93 to
      2.7 nmol/L (mean increase = 1.8 nmol/L) vs an increase from 0.47 to 4.81 nmol/L
      (mean increase = 4.32 nmol/L) in those with CDGP. All adolescents with CDGP, but
      only 7 the 12 thalassemic adolescents, had T secretion above 2 nmol/L after 6
      months of hCG therapy and maintained their growth and pubertal development for a
      year after stopping hCG. The 5 thalassemic patients with defective T secretion
      after hCG therapy had significantly higher ferritin level (1985 +/- 658 ng/mL) vs
      the other 7 patients (1100 +/- 425 ng/mL). These findings denoted significant
      testicular dysfunction in those patients with higher iron overload (testicular
      siderosis). Statural GV was significantly correlated with insulin-like growth
      factor 1 (IGF-1) concentrations and testicular diameter after hCG therapy (r =
      0.5 and 0.43 respectively, P < .001). In summary, hCG therapy was effective in
      treating 7 of 12 (58%) of thalassemic adolescents with delayed puberty. In the
      rest of patients (5/12, 46%) with significantly higher iron overload, hCG therapy
      failed to stimulate testicular growth and adequate T. Proper iron chelation
      appears to protect against testicular dysfunction. In the first group of
      patients, hCG therapy can be used for the treatment of their hypogonadism,
      whereas T replacement remains the therapy of choice for the second group.

PMID- 15562376
TI  - Effect of pioglitazone on body composition and energy expenditure: a randomized
      controlled trial.
AB  - BACKGROUND: Several clinical studies have demonstrated that body weight increases
      after treatment with thiazolidinediones (TZDs). Prior studies have demonstrated
      an increase in insulin-stimulated lipid storage in adipose tissue. Some, but not
      all, studies demonstrate reductions in visceral adipose tissue. Changes in body
      weight are the result of changes in energy intake, energy expenditure, or both.
      OBJECTIVES: Based on these findings, the primary aim of this study was to
      evaluate the effect of TZDs on visceral, subcutaneous, and total body fat.
      Secondary aims were to determine the effects of pioglitazone on (a) energy
      expenditure, (b) hunger and satiety, (c) blood lipids, and (d) the role of
      insulinemia/sulfonylurea usage on weight gain in patients with type 2 diabetes.
      SUBJECTS AND METHODS: We performed a randomized, double-blind, placebo-controlled
      trial in 48 men and women with type 2 diabetes who had not previously received
      treatment with TZDs. Patients were treated for 24 weeks with 45 mg/d of
      pioglitazone or a matching placebo. Body composition was measured by dual-energy
      x-ray absorptiometry. Visceral and subcutaneous fat were measured by computed
      tomography. Resting metabolic rate and thermogenic response to a test meal were
      measured by indirect calorimetry before and after a standardized meal. Hunger and
      satiety were measured with visual analog scales before and after the same test
      meal. Blood was collected for the measurement of fasting glucose and insulin
      levels, hemoglobin A 1c levels, and lipid content. RESULTS: Pioglitazone
      treatment resulted in a decrease in hemoglobin A(1c) level by 0.96 +/- 1.1% vs
      0.11 +/- 0.8% in the placebo group (P < .005). Body weight and fat increased
      steadily in the patients treated with pioglitazone during the 6 months of the
      study (+3.9 +/- 3.1 kg at 6 months in pioglitazone-treated patients vs -0.8 +/-
      3.4 kg in the placebo-treated patients). Subcutaneous fat in the trunk, arms, and
      legs were all increased in the pioglitazone-treated group. Visceral fat did not
      change significantly in either group. Neither resting metabolic rate nor the
      thermogenic responses to a meal were altered by pioglitazone. Subjective measures
      of hunger (visual analog scale) did not change with pioglitazone treatment.
      Triglycerides fell in the pioglitazone-treated group (-58.5 +/- 124 mg/dL, P <
      .003). Neither the prior use of sulfonylureas nor the level of insulinemia before
      treatment was a predictor of weight or fat change. CONCLUSION: Pioglitazone
      increased subcutaneous body fat, but not visceral fat. There was no measurable
      effect on energy expenditure or hunger/satiety. In contrast to the placebo
      treated patient with diabetes, weight gain occurs in the face of falling
      hemoglobin A(1c) and triglyceride levels.

PMID- 15562377
TI  - C-reactive protein levels and prevalence of chronic infections in subjects with
      hypoalphalipoproteinemia.
AB  - Low levels of high-density lipoprotein cholesterol (HDL-C) show a consistent
      relationship with the development of atherosclerosis. The underlying mechanisms
      are not well understood, but recent studies in subjects with primary
      hypoalphalipoproteinemia suggest that this could represent a proinflammatory
      condition. To better assess the link between HDL-C levels and C-reactive protein
      levels and the possible role of chronic infections as putative mediators of this
      relationship, we studied a population sample with nonselected causes of
      hypoalphalipoproteinemia. Eighty-six consecutive patients with HDL-C levels below
      40 mg/dL who attend our lipid clinic and 86 control subjects with normal
      concentrations matched for gender, age, smoking habit, and weight were included
      in the study. Mean HDL-C levels were 34 +/- 3.9 and 55.4 +/- 8.8 mg/dL for
      subjects with hypoalphalipoproteinemia and control subjects, respectively. C
      reactive protein concentrations were increased in case patients as compared with
      control subjects (2.13 +/- 2.0 vs 1.52 +/- 1.8 mg/L; P = .025). The prevalence of
      herpes simplex virus type 1, cytomegalovirus, Chlamydia pneumoniae , and
      Helicobacter pylori infections did not differ between the 2 groups. Although a
      possible confounding variable could be a degree of insulin resistance within the
      group of patients with low HDL-C levels, our results indicate that C-reactive
      protein levels are increased in subjects with nonselected
      hypoalphalipoproteinemia and that chronic infections do not appear to mediate
      this relationship.

PMID- 15562378
TI  - Effect of high plant sterol-enriched diet and cholesterol absorption inhibitor,
      SCH 58235, on plant sterol absorption and plasma concentrations in
      hypercholesterolemic wild-type Kyoto rats.
AB  - BACKGROUND AND AIMS: Plant sterols are widely distributed in human diet but are
      poorly absorbed so that their plasma levels are very low. However, when fed in
      large amounts, they lower plasma cholesterol levels by interfering with
      cholesterol absorption. We have studied the effect of 4 weeks of feeding a chow
      diet supplemented with 1% plant sterols [brassicasterol (6.3%), campesterol
      (28.5%), stigmasterol (15.6%) and sitosterol (49.6%)], with or without SCH 58235
      (a derivative of ezetimibe), 30 mg/kg per day, known to suppress intestinal
      cholesterol absorption, on plasma, tissue, biliary, and fecal sterols in Wistar
      and wild-type Kyoto (WKY) rats, and their metabolism by intestinal bacteria.
      METHODS: After 2 weeks of feeding control or experimental diet, rats were given
      [3alpha-(3)H]sitosterol intravenously and [4-(14)C]sitosterol by mouth, and blood
      was collected after 1, 2, 3, and 5 days after labeling to determine sitosterol
      absorption. Feces were collected during the last 3 days and freeze dried. At the
      end of feeding, bile fistulas were created in 3 rats of each strain and bile was
      collected for 1 hour. All rats were then sacrificed and plasma and liver were
      collected for sterol measurements and activities of hepatic HMG-CoA reductase,
      cholesterol 7alpha-hydroxylase, and cholesterol 27-hydroxylase. RESULTS: Wild
      type Kyoto rats were hypercholesterolemic compared to Wistar rats and had
      increased plant sterols in the plasma. Plasma cholesterol tended to be lower in
      WKY rats after feeding with plant sterol-enriched diet whereas plant sterol
      levels rose to approximately 31% of plasma sterols in WKY and 14% in Wistar rats.
      However, brassicasterol and stigmasterol, with a double bond at C-22, constituted
      less than 3.5% of total plasma plant sterols. After feeding, biliary plant
      sterols increased 2.25-fold in Wistar and 1.5-fold in WKY rats, suggesting less
      hepatic clearance in WKY rats. SCH 58235 feeding significantly increased plasma
      as well as biliary cholesterol levels in both the untreated and plant sterol-fed
      WKY rats, and the plasma plant sterols showed a tendency to increase but did not
      reach significant level. Intestinal bacteria in both rat strains metabolized all
      plant sterols to mainly the 5beta-H-stanols. However, the C-22 double bond was
      stable to bacterial degradation. Intestinal absorption of sitosterol and
      cholesterol was increased 1.5- and 1.3-fold, respectively, in the WKY rats as
      compared to the Wistar rats, and plant sterol feeding lowered absorption of these
      sterols in both strains. Absorption of both these sterols was also lowered in SCH
      58235-treated rats in both strains and was further lowered when SCH 58235 and
      plant sterols were simultaneously fed. The activity of the rate-limiting enzyme,
      HMG-CoA reductase, was increased 1.57-fold in Wistar rats and 1.27-fold in WKY
      rats that were fed plant sterols as compared to untreated rats. CONCLUSIONS: (1)
      Plant sterol absorption was increased whereas hepatic elimination of all sterols
      was diminished in WKY rats accounting for elevated cholesterol and plant sterol
      levels. (2) The 1% plant sterol-enriched diet tended to lower plasma cholesterol
      levels whereas SCH 58235 feeding significantly increased plasma cholesterol
      levels in the WKY rats. (3) Intestinal absorption of sterols with C-22 double
      bond is diminished and the side-chain double bond is resistant to intestinal
      bacteria.

PMID- 15562379
TI  - Circulating osteoprotegerin levels are associated with age, waist-to-hip ratio,
      serum total cholesterol, and low-density lipoprotein cholesterol levels in
      healthy Korean women.
AB  - Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy
      receptor for the receptor activator of nuclear factor I masculine B ligand.
      Osteoprotegerin has been shown to be an important inhibitor of osteoclastogenesis
      and arterial calcification in animal models. Recently, OPG has been proposed as a
      link molecule between osteoporosis and arterial calcification, but the
      relationship between circulating OPG levels and cardiovascular disease in human
      populations is unclear. Thus, the aim of this study was to investigate the
      relationship between circulating OPG levels and cardiovascular risk factors in
      healthy Korean women. The subjects were 286 women aged 37 to 73 (mean +/- SD,
      51.5 +/- 6.9 years). We examined blood pressure, body mass index, and waist-to
      hip ratio. Serum concentrations of OPG were determined by enzyme-linked
      immunosorbent assay. Fasting plasma glucose levels, serum lipid profiles, insulin
      levels, and serum follicle-stimulating hormone (FSH) levels were determined by
      standard methods and homeostasis model assessment of insulin resistance was
      calculated. We observed a significant association between serum OPG levels and
      age, waist-to-hip ratio, total cholesterol, low-density lipoprotein cholesterol,
      and FSH levels (P < .05). Among the metabolic components, the older, obese, and
      hypercholsterolemic subjects had higher serum OPG levels (P < .05). However, no
      significant relationship was found between serum OPG levels and blood pressure
      and fasting plasma glucose levels. We found that mean serum OPG levels were about
      11% greater in postmenopausal women (mean +/- SD, 1358.5 +/- 380.0 pg/mL) than in
      premenopausal women (mean +/- SD, 1228.8 +/- 407.7 pg/mL, P < .001). In multiple
      regression analysis with OPG as the dependent variable, serum FSH and low-density
      lipoprotein cholesterol levels were the significant predictor for serum OPG level
      (R(2) = 0.051, P < .05). In conclusion, our results show that circulating OPG
      levels are partly associated with cardiovascular risk factors and menopausal
      status in healthy Korean women. Out findings suggest that OPG may be an important
      paracrine factor of cardiovascular disease in the female population.

PMID- 15562380
TI  - Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and
      usefulness of pioglitazone for its treatment.
AB  - Here we demonstrate 2 patients who showed marked hyperglycemia after androgen
      deprivation therapy for prostate cancer and the efficacy of the thiazolidinedione
      pioglitazone on their glycemic control. Case 1 was a 61-year-old man diagnosed
      with prostate cancer who had type 2 diabetes mellitus for 7 years. His glycemic
      control had been good for the previous 5 years because of diet therapy and
      acarbose administration. He was given the gonadotropin-releasing hormone agonist
      leuprolide acetate and the androgen receptor antagonist flutamide for the
      treatment of prostate cancer. After the second injection of leuprolide acetate,
      fasting glucose and hemoglobin A1c (HbA1c) levels were found to be markedly
      elevated (22.8 mmol/L and 10.5%, respectively). Case 2 was an 81-year-old man
      whose fasting glucose and HbA1c had been normal 10 months ago. He was injected
      with leuprolide acetate for the treatment of prostate cancer. Six months after
      starting the leuprolide treatment, the patient complained of thirst and weight
      loss and was diagnosed with diabetes mellitus with a fasting glucose of 19.4
      mmol/L and HbA1c of 9.9%. The correct homeostasis model assessment evaluation
      indexes for pancreatic beta-cell function (HOMA-%beta )A and for insulin
      sensitivity (HOMA-%S) were reduced in these 2 patients compared with control men.
      Their serum testosterone and 17beta -estradiol concentrations were depressed.
      After improvement of hyperglycemia by insulin treatment, their glycemic control
      remained good after treatment with pioglitazone without use of insulin. The
      values of HOMA-%beta and HOMA-%S increased to control ranges. Insulin resistance
      after the androgen-deprivation therapy might lead to marked hyperglycemia in
      these patients.

PMID- 15562381
TI  - Adiponectin and glucose production in patients infected with Plasmodium
      falciparum.
AB  - Infections are often complicated by an increase in glucose production due to
      stimulation of the secretion of glucose counter-regulatory hormones and
      cytokines. Adiponectin, a fat-derived hormone with insulin-sensitizing
      properties, could play a regulatory role in the degree of stimulation of glucose
      production by the infectious agent. Therefore, we investigated the possible
      correlation between glucose production and plasma adiponectin levels in 25
      subjects: 7 patients with cerebral malaria, 6 with uncomplicated malaria, and 12
      matched controls. Glucose production was significantly higher in patients with
      malaria compared to healthy controls (P < .001). Adiponectin levels were not
      different between the patients with malaria and the control group. However,
      patients with cerebral malaria had significantly higher values for adiponectin
      than the patients with uncomplicated malaria (P < .005). Glucose production and
      gluconeogenesis were positively correlated to plasma adiponectin in the patients
      (r = 0.835, P < .001 and r = 0.846, P < .001, respectively), whereas these
      correlations were absent in the controls (r = -0.329, NS and r = -0.028, NS,
      respectively). In conclusion, adiponectin levels were not different between
      patients with malaria and their matched controls. However, patients infected with
      Plasmodium falciparum who have higher glucose production also have higher
      adiponectin levels. In healthy subjects such a correlation was not found. As
      adiponectin is known to inhibit glucose production, stimulation of adiponectin
      secretion during infection could be intended to restrain the glucose production
      stimulating properties of hormones and cytokines secreted during infection.

PMID- 15562382
TI  - Effects of diacylglycerol administration on serum triacylglycerol in a patient
      homozygous for complete lipoprotein lipase deletion.
AB  - We investigated postprandial and long-term effects of dietary diacylglycerol
      (DAG) on serum triacylglycerol (TAG) levels in a 34-year-old man homozygous for
      complete lipoprotein lipase deletion (LPL deletion). In study 1, Three different
      oils (DAG, TAG, or medium-chain fatty acid TAG [MCT]) were ingested to examine
      differences in the postprandial serum TAG response. Postprandial serum TAG levels
      after DAG oil ingestion were lower than those after TAG oil ingestion and similar
      to those after MCT oil ingestion. In study 2, the patient was allowed to ingest
      ordinary cooking oil for 2 months and then DAG oil (containing 80% DAG; target,
      20 g/d) for the next 3 months. During the test period, serum TAG levels were
      measured and dietary evaluations were performed every month. The patient was
      provided with dietary instruction and consultation at each clinical visit. Serum
      TAG levels were 1939 to 2525 mg/dL when he used ordinary cooking oil, 1926 to
      1173 mg/dL when he used ordinary cooking oil together with DAG oil, and 749 mg/dL
      when he used DAG oil alone. The TAG intake decreased from 86.9 to 43.0 g and the
      DAG intake increased from 0.9 to 12.4 g during the study period. Subsequently, 45
      g DAG oil (equivalent to 36 g DAG) per day was consumed, and the serum TAG level
      increased to 2195 mg/dL. Although there was a positive correlation between the
      TAG intake and serum TAG levels during the period of DAG oil use (P < .01, y =
      33.7x - 583.1), there was no such correlation between DAG oil intake and serum
      TAG levels. These results suggested that substitution of 12.0 g/d DAG (equivalent
      to 15 g DAG oil) for TAG oil had the same effect as reducing TAG oil consumption
      for controlling the serum TAG levels in an LPL-depleted patient with
      hypertriglyceridemia. In conclusion, the results of study 1 and study 2
      demonstrate that DAG oil might be replaced by MCT oil as cooking oil for those
      with LPL deletion.

PMID- 15562383
TI  - Does the type of hormone replacement therapy affect lipoprotein (a),
      homocysteine, and C-reactive protein levels in postmenopausal women?
AB  - BACKGROUND: The results of studies evaluating the effect of hormone replacement
      therapy (HRT) on the cardiovascular risk raise many controversies. This may be
      related to both the type of treatment used and the disregard of additional risk
      factors. OBJECTIVE: The objective of the study was to evaluate the effect of
      natural estrogens taken transdermally and synthetic estrogens taken orally on the
      concentrations of lipoprotein (a) [Lp(a)], homocysteine, and C-reactive protein
      (CRP) in healthy women in the early postmenopausal period. Material The study was
      conducted on 61 healthy women with average age of 52.3 +/- 4.1 years, in the
      postmenopausal period, who were randomly assigned to 3 groups depending on the
      type and route of administration of the products. Group I (n = 24) was
      administered transdermal estrogens (micronized 17beta-estradiol; Systen, Janssen
      Cilag, Switzerland) and progesterone in the second phase of the cycle. Group II
      (n = 21) was administered oral hormones (Cyclo-Menorette). Group III (n = 16),
      serving as a control, included women taking placebo in the form of patches. In
      each group, therapeutic cycles took 22 days and were followed by a treatment-free
      interval of 7 to 10 days for a 3-month period. RESULTS: After 3 months of
      treatment, Lp(a) and homocysteine levels were not significantly different from
      the baseline, irrespective of the route of administration of estrogens or
      placebo. Both forms of HRT used indicate significant difference in changes of CRP
      concentration during 3 months of administration (analysis of variance P = .0356).
      CRP concentration values increased in the group of women using oral HRT from 1.22
      to 2.68 mg/L. In the group of women using oral therapy, significantly more cases
      (61%) of increase in CRP concentration compared with 39% in the transdermal HRT
      group (chi(2) P = .015) were observed. CONCLUSIONS: On the basis of our
      observations, it appears that in women in the early postmenopausal stage with
      normal initial concentrations of Lp(a) and homocystein, the form of therapy used
      has no influence on values of these parameters. The 2 forms of HRT therapy differ
      in effect, which is expressed as a change in CRP concentration. A tendency to
      increase CRP values when using oral HRT is observed, while such an effect is not
      observed in case of transdermal therapy after 3 months.

PMID- 15562384
TI  - Effect of repaglinide and gliclazide on postprandial control of endogenous
      glucose production.
AB  - The effect of repaglinide and gliclazide on postmeal suppression of endogenous
      glucose production (EGP) has been studied using a variable-rate tracer
      methodology. Groups of age-, sex-, and weight-matched type 2 diabetic subjects
      randomized to gliclazide or repaglinide were studied after ingesting a standard
      mixed meal (550 kcal; 67% carbohydrate, 19% fat, 14% protein). Plasma glucose
      profiles were similar in each group and markedly different from that of a
      nondiabetic control group. Endogenous glucose production was similar basally
      (3.01 +/- 0.30 vs 3.06 +/- 0.19 mg/kg per minute, gliclazide and repaglinide,
      respectively). After glucose ingestion, EGP declined rapidly in both the groups
      until 30 minutes and the greatest suppression was reached earlier in the
      repaglinide group [0.88 mg/kg per minute at 120 minutes vs 0.77 mg/kg per minute
      at 210 minutes in gliclazide group (P < .05); median time, 85 vs 195 minutes,
      respectively (P < .05)]. The area under the curve (30-150) for EGP was
      significantly greater in the gliclazide group than in the nondiabetic control
      group (109 +/- 11 vs 198 +/- 22 mg/kg per min 2 ; P > .02) but not significantly
      different in the repaglinide group (153 +/- 25 mg/kg per min 2 ; P = .17).
      Repaglinide has minimal physiological advantage over gliclazide, but both
      therapies for type 2 diabetes fall far short of correcting the endocrine and
      metabolic abnormalities.

PMID- 15562385
TI  - Effects of alendronate on bone mineral density and bone metabolic markers in
      postmenopausal asthmatic women treated with inhaled corticosteroids.
AB  - We have recently shown that long-term use of inhaled corticosteroids decreases
      bone mineral density (BMD) of the lumbar spine in postmenopausal asthmatic women.
      The present study aimed to evaluate the efficacy of alendronate in comparison
      with that of alfacalcidol (1-alpha-hydroxyvitamin D(3)) for the treatment of BMD
      reduction in postmenopausal asthmatic patients who had inhaled corticosteroid
      therapy without regular use of systemic corticosteroids. Twenty-eight
      postmenopausal asthmatic patients with BMD T score of -1.0 or less were
      randomized to receive alendronate (5 mg/d) or alfacalcidol (1 microg/d). Bone
      mineral density was determined at baseline and 12 months after the treatment, and
      biochemical markers of bone metabolism were measured at baseline and after 6 and
      12 months of treatment. The mean (+/-SD) BMD values at the lumbar spine, the
      total hip, and the Ward's triangle significantly increased by 4.9 +/- 4.5% (P =
      .0005), 2.4 +/- 2.2% (P = .0005), and 3.6 +/- 5.2% (P = .02) at 12 months in the
      alendronate group, whereas the corresponding values did not significantly change
      in the alfacalcidol group. In the alendronate group, urinary N-telopeptide (NTx),
      serum osteocalcin, and serum alkaline phosphatase concentrations significantly
      decreased, and serum intact parathyroid (PTH) level significantly increased, from
      baseline at both 6 and 12 months. In the alfacalcidol group, urinary NTx showed
      modest but significant decrease, although the extent of the change was smaller
      than that in the alendronate group. We concluded that alendronate was effective
      to improve reduced BMD in postmenopausal asthmatic patients on inhaled
      corticosteroid therapy through the mechanism of inhibiting bone resorption.

PMID- 15562386
TI  - Racial difference in circulating sex hormone-binding globulin levels in
      prepubertal boys.
AB  - Racial differences in disease risk (eg, osteoporosis, metabolic cardiovascular
      syndrome, and prostate cancer) may arise partly on a hormonal basis. While
      reports of racial differences in gonadal steroid hormone levels in middle-aged
      men have produced conflicting results, there is evidence that high sex hormone
      binding globulin (SHBG) and estradiol levels are more common among young adult
      African American men than white men. To determine whether this difference relates
      to pituitary-testicular functioning or to other factors, we conducted a cross
      sectional study of 47 healthy prepubertal African American and white boys aged 5
      to 9 years at the time of their annual school physical examination. Height,
      weight, blood pressure, waist and hip circumference, and Tanner staging were
      determined, and a fasting blood sample was obtained. The African Americans
      studied were slightly older than the whites (mean +/- SD, 82.4 +/- 15.0 vs 70.5
      +/- 10.3 months, P = .003). African Americans were also slightly taller and
      heavier and had a lower waist-to-hip ratio, but these differences could be
      explained by the difference in age. Mean SHBG levels were 25% higher (P = .15) in
      African Americans than in whites (197 +/- 104 vs 157 +/- 79 nmol/L), and when
      adjusted for age, values were 46 nmol/L higher among African Americans. The fifth
      quintile for SHBG (values > 245 nmol/L) included 1 (4.2%) of 24 whites and 8
      (35%) of 23 African Americans studied (P = .003). There was no significant
      correlation between age, body mass index, waist circumference, or fasting insulin
      and SHBG. Total testosterone, the free androgen index, and dehydroepiandrosterone
      increased with age in both groups, but after adjusting for age, no racial
      differences were found. Estradiol, estrone, and inhibin B levels, as well as
      systolic and diastolic blood pressures, were also comparable in both groups. We
      conclude that high levels of SHBG are more common among African American than in
      white boys and hypothesize that this difference and its effect on the ratio
      between bound and free steroid hormones may contribute to racial differences in
      disease risk in adult men.

PMID- 15562387
TI  - Endurance training-induced changes in the insulin response to oral glucose are
      associated with the peroxisome proliferator-activated receptor-gamma2 Pro12Ala
      genotype in men but not in women.
AB  - The present study sought to investigate, in sedentary men and women, (a) whether
      a common functional gene variant (peroxisome proliferator-activated receptor
      gamma2 [PPARgamma2] Pro12Ala) predicts insulin action and (b) whether
      improvements in insulin action in response to endurance exercise training are
      associated with PPARgamma2 Pro12Ala. Sedentary, 50- to 75-year-old men and women
      (N = 73) were genotyped and underwent oral glucose tolerance tests (OGTTs) before
      and after 6 months of endurance training. At baseline, men heterozygous for the
      Pro12Ala variant had a greater OGTT insulin area under the curve (AUC) as
      compared with Pro12 homozygous men (P = .009). Endurance training resulted in a
      significantly greater improvement in insulin AUC in Pro12Ala heterozygous men as
      compared with Pro12 homozygous men (P = .003) despite no genotype-specific
      differences with respect to training-induced changes in body weight, body mass
      index, and percent body fat. No differences between genotype groups were present
      at baseline or in response to training in women. Training did not alter the OGTT
      glucose AUC for the group as a whole, and the baseline, final, and change in
      glucose AUC were not dependent on PPARgamma2 genotype and/or sex. In conclusion,
      these findings suggest that sedentary men with the PPARgamma2 Pro12Ala variant
      have lower insulin action on glucose disposal as compared with their
      counterparts. However, these men are particularly responsive with respect to the
      magnitude of endurance training-induced improvement in insulin action.

PMID- 15562388
TI  - Effect of antibiotics as cholesterol-lowering agents.
AB  - Antibiotics were once proposed as hypercholesterolemic agents although the
      mechanism is unclear, despite broad implications, including providing an
      alternative approach to cholesterol reduction, with potential relevance for
      current trials of antibiotics to reduce cardiovascular disease, and possible
      confounding of routine diagnostic cholesterol measurements. The effect on serum
      lipids of antibiotics against aerobes and anaerobes, together with possible
      mechanisms, was therefore explored. Twenty-two men and women took antibiotics for
      10 days (either ciprofloxacin for 13 subjects or metronidazole for 10 subjects),
      with 10 days control in random order separated by 2-week washout periods.
      Subjects maintained low-fat diets throughout the study. Blood samples and blood
      pressure were obtained on days 0 and 10 of each phase with 3-day fecal
      collections and 12-hour breath gas collections at the end of each phase. The
      results indicated that metronidazole markedly reduced low-density lipoprotein
      cholesterol (-14.0 +/- 4.0%, P = .006), oxidized low-density lipoprotein (-23.0
      +/- 5.1%, P = .002), and the apolipoprotein B/A-I ratio (-18.0 +/- 2.8%, P <
      .001), whereas the reduction with ciprofloxacin was less pronounced
      (apolipoprotein B/A-I, -5.0 +/- 1.8%, P = .017). Neither antibiotic altered C
      reactive protein or blood pressure. The low-density lipoprotein cholesterol
      reduction related to an increase in bifidobacteria (r = -0.46, P = .029), but not
      to markers of colonic fermentation. We conclude that antibiotics can reduce serum
      lipids acutely. These effects may confound diagnostic measurements but indicate
      possible links between colonic microflora and blood lipids and the need to study
      ways of altering colonic microflora by nonantibiotic means as a potential
      therapeutic option.

PMID- 15562389
TI  - Metformin-diet benefits in women with polycystic ovary syndrome in the bottom and
      top quintiles for insulin resistance.
AB  - We prospectively assessed whether metabolic and menstrual benefits of metformin
      diet were equally realized in women with polycystic ovary syndrome (PCOS),
      categorized by pretreatment top (n = 32) and bottom (n = 35) quintile homeostasis
      model assessment insulin resistance (IR). Effects of metformin (2.55 g/d) and
      diet (6300-8400 J/d [1500-2000 cal/d], 26% protein, 44% carbohydrate) were
      prospectively assessed for 12 months. Pretreatment, the bottom and top insulin
      resistant quintile groups differed by median weight (84 vs 121 kg), insulin (7.8
      vs 40.5 I(1/4) U/mL), IR (1.62 vs 9.28), homeostasis model assessment insulin
      secretion (131 vs 416), glucose (82 vs 98 mg/dL), sex hormone-binding globulin
      (40 vs 15 nmol/L), (all P < .0001), free androgen index (2.76 vs 10.8) ( P <
      .001), triglyceride (92 vs 131 mg/dL), high-density lipoprotein (46 vs 39 mg/dL),
      systolic blood pressure (116 vs 128 mm Hg), and diastolic blood pressure (76 vs
      84 mm Hg), (all P < .01). After 12 months on metformin-diet, weight fell by 7% in
      both insulin-resistant groups (P < .0001), insulin, IR, and insulin secretion
      fell in the top insulin-resistant group by 60%, 64%, and 39% (all P < .0001),
      with smaller reductions in the bottom insulin-resistant group of 18%, 13% (P >
      .05 for both), and 22% (P < .01), respectively. The free androgen index fell 39%
      (P > .01) in the top insulin-resistant group. The pretreatment percentage of
      expected menses in the top insulin-resistant quintile (26 +/- 39%) was 1.6 times
      less than in the bottom insulin-resistant quintile (41 +/- 38%) (P = .026). Over
      the 12-month treatment period, the percentage of spontaneous regular normal
      menses increased to 72 +/- 27% in the top insulin-resistant quintile group (P <
      .0001) and to 77 +/- 31% in the bottom quintile group (P < .0001), with no group
      difference (P = .33). Metformin-diet metabolic effects were much more marked in
      women in the top vs the bottom quintile for IR. Women with PCOS in the bottom
      insulin-resistant quintile, conventionally thought not to respond optimally to
      metformin-diet, nevertheless experience significant metabolic and menstrual
      benefits. Metformin-diet should benefit most women with PCOS, even those with
      normal serum insulin, without IR.

PMID- 15562390
TI  - Differential regulation of atrial natriuretic peptide- and adrenergic receptor
      dependent lipolytic pathways in human adipose tissue.
AB  - The aim of the study was to investigate the regulation affecting the recently
      described atrial natriuretic peptide (ANP)-dependent lipolytic pathway in
      comparison with the adrenergic lipolytic cascade. We studied in vivo the effect
      of a euglycemic-hyperinsulinemic clamp on the changes occurring in the
      extracellular glycerol concentration (EGC) of subcutaneous adipose tissue (SCAT)
      during ANP or epinephrine perfusion in a microdialysis probe. Homologous
      desensitization and the incidence of hyperinsulinemia on the ANP- and
      catecholaminergic-dependent control of lipolysis were also investigated in vitro
      on fat cells from SCAT. When perfused in SCAT, epinephrine and ANP promoted an
      increase in EGC; the EGC increase was significantly lower during the clamp. The
      reduction of epinephrine-induced lipolysis was limited (18%) when phentolamine
      (an alpha(2)-adrenergic receptor [AR] antagonist) was perfused together with
      epinephrine. Unlike the effect of epinephrine, the response to ANP observed
      during the second perfusion was reduced by 32%. The increase in extracellular
      guanosine 3',5' -cyclic monophosphate concentration, which reflects ANP activity,
      was also reduced during the second perfusion. Desensitization of the lipolytic
      effects of ANP was observed in vitro after a 2-hour period of recovery, while the
      effects of alpha(2)-AR agonist or of epinephrine were unchanged. Insulin was
      without any effect on ANP-induced lipolysis and alpha(2)-AR-mediated
      antilipolysis, while it reduced beta-AR-induced lipolysis. The ANP-dependent
      lipolytic pathway undergoes desensitization in vitro and in situ. Insulin had no
      inhibitory effect on either ANP- or alpha(2)-AR-dependent pathways, while it
      counteracted the beta-AR pathway.

PMID- 15562391
TI  - High lipoprotein lipase activity increases insulin sensitivity in transgenic
      rabbits.
AB  - Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of
      triglyceride-rich lipoproteins and plays an important role in glucose metabolism.
      To examine the hypothesis that increased LPL activity may alter insulin
      sensitivity, we investigated glucose metabolism and insulin sensitivity in
      transgenic (Tg) rabbits expressing the human LPL gene under the control of a I(2)
      -actin promoter. An intravenous glucose tolerance test showed that the plasma
      glucose clearance rate was not significantly different between Tg and non-Tg
      rabbits; however, the area under the curve for insulin and free fatty acids in Tg
      rabbits was significantly reduced compared with that of non-Tg rabbits (P < .05).
      Using the intravenous insulin tolerance test, we found that the area of under the
      curve of glucose of Tg rabbits was also significantly reduced (P < .01).
      Furthermore, euglycemic-hyperinsulinemic clamp test revealed that the mean
      glucose infusion rate in Tg rabbits was significantly higher than in non-Tg
      rabbits (P < .05). These results demonstrate that systemic overexpression of LPL
      increases whole-body insulin sensitivity and genetic manipulation of LPL genes
      may be a potential target for the treatment of diabetic patients.

PMID- 15562392
TI  - Apolipoprotein E polymorphism in Vietnamese children and its relationship to
      plasma lipid and lipoprotein levels.
AB  - We investigated the frequency of apolipoprotein E (apoE) polymorphism and the
      effect of apoE polymorphism on plasma lipid and lipoprotein levels under
      different nutritional statuses in Vietnamese children living in urban and rural
      areas. Three hundred and forty-eight girls (aged 7 to 9 years) were randomly
      selected from urban and rural areas in southern Vietnam. Their apoE genotypes
      were analyzed by an Invader assay, and the plasma lipid and lipoprotein levels
      were determined by enzymatic methods using fasting blood samples. Dietary intake
      and anthropometry of children were also measured. The frequency of the allele
      epsilon 2 and epsilon 4 of the Vietnamese girls was 0.09 and 0.12, respectively.
      The levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol
      (TC) of the allele epsilon 2 carriers were significantly lower than those of the
      allele epsilon 3 carriers (P < .0001) in both the urban and rural groups. In
      contrast, the allele epsilon 4 carriers tended to show a higher LDL-C level than
      the allele epsilon 3 carriers, especially in subjects with a higher fat intake in
      urban area. The allele epsilon 2 carriers had the same high-density lipoprotein
      cholesterol (HDL-C) and triglyceride (TG) level as the allele epsilon 3 carriers,
      but the allele epsilon 4 carriers with a higher fat intake living in urban areas
      had lower HDL-C and higher TG level than allele epsilon 3 carriers. In
      conclusion, our findings showed that the LDL-C lowering effect of allele epsilon
      2 was independent of the nutritional status, while allele epsilon 4 tended to
      lower HDL-C and increase the LDL-C level in a high-fat intake population.
      Therefore, the plasma lipid profiles of apoE epsilon 4 carriers may be a risk
      factor of atherogenesis in Vietnamese, who tend to have a westernized eating
      habit.

PMID- 15562393
TI  - Comparative evaluation of simple indices of insulin resistance.
AB  - Various surrogate methods for the quantification of insulin sensitivity have been
      proposed. A comparative evaluation is lacking and is relevant for the
      standardization of investigative methods and comparability of results. The aims
      of the study were to perform a comparative validation of fasting insulin,
      homeostasis model assessment (HOMA), Quantitative Insulin Sensitivity Check Index
      (QUICKI), and revised-QUICKI (R-QUICKI) against minimal model derived estimates
      of insulin sensitivity (SI(MM)) in nondiabetic people and to carry out a
      comparative evaluation of the ability of these indices as means for the
      identification of individuals with the metabolic syndrome (MS) on a population
      basis. We used 2 data sets defined as "validation sample" and "prevalence
      sample". Validation sample: a total of 162 healthy men and women aged 30 to 65
      years were studied by frequently sampled intravenous glucose tolerance test
      (FSIVGTT). SI(MM) was calculated with the Minmod program. Prevalence sample: a
      total of 2,731 nondiabetic men and women aged 35 to 65 years were studied. In
      both samples, anthropometry, blood pressure, fasting glucose, insulin,
      triglycerides, high-density lipoprotein (HDL) cholesterol, and free fatty acid
      (FFA) were measured. HOMA, QUICKI, and R-QUICKI were calculated. The MS was
      defined according to the Adult Treatment Panel III. Validation sample: insulin,
      HOMA, QUICKI, and R-QUICKI significantly correlated with SI(MM) (r = -0,53, 
      0.52, 0.41, 0.33; all P < .001). The finding was confirmed in obese (body mass
      index [BMI] > or =25 kg/m(2)), but in the normal weight, the correlation
      coefficient for QUICKI was significantly smaller than for the other indices.
      Receiver operator characteristic (ROC) curve analysis performed with SI(MM) below
      or above the lowest 25th percentile (ie, insulin resistance yes, no) as the
      outcome variable and each of the 4 indices as the test variable showed no
      significant differences in the areas under the curve. Prevalence sample:
      prevalence of the MS progressively increased across quartiles of insulin
      resistance as evaluated by any of the 4 indices, with no significant differences
      between them. The novel indices QUICKI and R-QUICKI do not perform better than
      HOMA and fasting insulin as surrogate measures of insulin resistance or means for
      the identification of people with MS in the general population.

PMID- 15562394
TI  - Functional characterization of mutant CYP17 genes isolated from a 17 alpha
      hydroxylase/17,20-lyase-deficient patient.
AB  - CYP17 has a dual enzymatic activity that is necessary for steroid hormone
      biosynthesis. It catalyzes the 17 alpha-hydroxylation of progesterone or
      pregnenolone and also removes an acetyl moiety of hydroxy-progesterone or
      hydroxypregnenolone by its 17,20-lyase activity to produce androstenedione or
      dehydroepiandrosterone (DHEA), respectively. We previously isolated a compound
      heterozygous mutant of CYP17 from a Korean female patient: 1-base deletion and 1
      base transversion mutation at 1 allele and 3-base deletion mutation at the other
      allele. Here we tested the functional activities of these 2 mutant CYP17 alleles
      using a transfection analysis in COS-1 cells with radiolabeled substrates and
      thin layer chromatography. Both mutant CYP17 genes lost not only 17 alpha
      hydroxylation activity, but also 17,20-lyase activity in this assay system. This
      nonfunctional nature of 2 mutant CYP17 genes explains the clinical manifestation
      of a patient who had 17 alpha-hydroxylase deficiency.

PMID- 15562395
TI  - Antidiabetic and adipogenic properties in a newly synthesized thiazolidine
      derivative, FPFS-410.
AB  - We report here a newly synthesized cyanoimino-oxothiazolidine derivative, FPFS
      410, which has properties to ameliorate both hyperglycemia and dyslipidemia.
      Treatment of genetically obese-diabetic db/db mice with FPFS-410 markedly
      ameliorates severe hyperglycemia and hypertriglyceridemia. Although the
      oxothiazolidine ring of FPFS-410 shares a structural similarity with other
      thiazolidinedione derivatives, reporter assays showed that FPFS-410 was much less
      potent to activate peroxisome proliferators-activated receptor gamma (PPAR gamma)
      as compared with pioglitazone. When 3T3-L1 preadipocytes were treated with FPFS
      410, intracellular accumulation of lipids was facilitated in a similar fashion to
      pioglitazone. Moreover, treatment with FPFS-410 throughout the differentiation
      course resulted in a significant increase in glucose transport. These results
      suggest that FPFS-410 may provide a useful therapeutic candidate for diabetes
      mellitus and dyslipidemia.

PMID- 15562396
TI  - Effects of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala
      polymorphism on body fat distribution in female Korean subjects.
AB  - The effects of peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2)
      Pro12Ala (P12A) polymorphism on body mass index (BMI) and type 2 diabetes are
      well documented; however, until now, only a few studies have evaluated the
      effects of this polymorphism on body fat distribution. This study was conducted
      to elucidate the effects of this polymorphism on computed tomography (CT)
      measured body fat distribution and other obesity-related parameters in Korean
      female subjects. The frequencies of PPAR gamma 2 genotypes were: PP type, 93.0%;
      PA type, 6.8%; and AA type, 0.2%. The frequency of the A allele was 0.035. Body
      weight (P = .012), BMI (P = .012), and waist-to-hip ratio (WHR) (P = .001) were
      significantly higher in subjects with PA/AA compared with subjects with PP. When
      body composition was analyzed by bioimpedance analysis, lean body mass and body
      water content were similar between the 2 groups. However, body fat mass (P =
      .003) and body fat percent (P = .025) were significantly higher in subjects with
      PA/AA compared with subjects with PP. Among overweight subjects with BMI of
      greater than 25, PA/AA was associated with significantly higher abdominal
      subcutaneous fat (P = .000), abdominal visceral fat (P = .031), and subcutaneous
      upper and lower thigh adipose tissue (P = .010 and .013). However, among lean
      subjects with BMI of less than 25, no significant differences associated with
      PPAR gamma 2 genotype were found, suggesting that the fat-accumulating effects of
      the PA/AA genotype were evident only among overweight subjects, but not among
      lean subjects. When serum lipid profiles, glucose, and liver function indicators
      were compared among overweight subjects, no significant difference associated
      with PPAR gamma 2 genotype was found. Changes in body weight, BMI, WHR, and body
      fat mass were measured among overweight subjects who finished a 1-month weight
      lose program of a hypocaloric diet and exercise; no significant differences
      associated with PPAR gamma 2 genotype were found. The results of this study
      suggest that the PPAR gamma 2 PA/AA genotype is associated with increased
      subcutaneous and visceral fat areas in overweight Korean female subjects, but
      does not significantly affect serum biochemical parameters and outcomes of weight
      loss programs.

PMID- 15562397
TI  - Relationship of intracellular magnesium of cord blood platelets to birth weight.
AB  - Magnesium (Mg(2+)) has an important role in insulin action, and insulin
      stimulates Mg(2+) uptake in insulin-sensitive tissues. Impaired biologic
      responses to insulin are referred to as insulin resistance. Diabetic patients and
      obese subjects are reported to have intracellular magnesium ([Mg(2+)](i))
      deficiency. Many epidemiologic studies have disclosed that restricted fetal
      growth has been associated with increased risk of insulin resistance in adult
      life. We studied the relationship of [Mg(2+)](i) in cord blood platelets to birth
      weight. The subjects were 19 infants who were small for gestational age (SGA) and
      45 who were appropriate for gestational age (AGA). By using a fluorescent probe,
      mag-fura-2, we examined the basal and insulin-stimulated [Mg(2+)](i) of platelets
      in the cord blood. Cord plasma insulin-like growth factor-1 (IGF-1)and leptin
      levels were determined with the use of enzyme-linked immunosorbent assay (ELISA).
      Birth weight was correlated with cord plasma IGF-1 (P < .001) and leptin (P <
      .005). Mean basal [Mg(2+)](i), but not plasma Mg(2+), was lower in the SGA than
      in the AGA group (291 +/- 149 micromol/L v 468 +/- 132 micromol/L, P < .001). The
      basal [Mg(2+)](i) was significantly correlated with the birth weight (P < .001)
      as well as birth length (P < .001). At 60 seconds after stimulation with insulin,
      there was no significant difference in stimulated [Mg(2+)](i) between the SGA and
      AGA groups. Although the SGA group had low [Mg(2+)](i), the platelets had good
      potentiality to compensate for low [Mg(2+)](i). [Mg(2+)](i) reflects the extent
      of fetal growth. Decreased [Mg(2+)](i) in SGA might underlie the initial
      pathophysiologic events leading to insulin resistance.

PMID- 15562398
TI  - Pro12Ala substitution in peroxisome proliferator-activated receptor gamma 2 is
      associated with low adiponectin concentrations in young Japanese men.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to
      play an important role in adipocyte differentiation. A Pro12Ala substitution in
      PPAR gamma 2 has been reported to decrease receptor activity in vitro and to be
      associated with a decreased risk of type 2 diabetes in the general population.
      Recently, a PPAR response element (PPRE) was identified in the adiponectin
      promoter, suggesting that decreased PPAR gamma activity may lead to lower
      adiponectin levels. In the present study, serum adiponectin concentrations and
      the PPAR gamma Pro12Ala polymorphism were analyzed to determine whether this
      polymorphism is associated with lower serum adiponectin concentrations in young
      healthy Japanese subjects. Serum adiponectin concentrations were significantly
      lower in men with than in those without the Ala12 allele, whereas body mass index
      (BMI), homeostasis model assessment (HOMA)-beta, HOMA-IR, the insulin sensitivity
      index during oral glucose tolerance test (ISI [composite]), and serum leptin did
      not differ significantly between subjects with and without the Ala12 allele.
      Stepwise regression demonstrated BMI and the Ala12 allele to be independent
      predictors of serum adiponectin concentrations in men. In conclusion, the
      Pro12Ala substitution in PPAR gamma 2 may reduce serum adiponectin concentrations
      in young Japanese men.

PMID- 15562399
TI  - Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin
      secretion in high-risk African Americans with impaired glucose tolerance test and
      type 2 diabetes.
AB  - We examined the metabolic effects of rosiglitazone therapy on glucose control,
      insulin sensitivity, insulin secretion, and adiponectin in first-degree relatives
      of African Americans with type 2 diabetes (DM) with impaired glucose tolerance
      (IGT) and DM for 3 months. The study was comprised of 12 first-degree relatives
      with IGT, 17 newly diagnosed DM, and 19 healthy relatives with normal glucose
      tolerance (NGT). Oral glucose tolerance test (OGTT) was performed before and
      after 3 months of rosiglitazone therapy (4 to 8 mg/d) in patients with IGT and
      DM. Serum glucose, insulin, C-peptide, and adiponectin levels were measured
      before and 2 hours during OGTT in the NGT and patients with IGT and DM. Insulin
      resistance index (HOMA-IR) and beta-cell function (HOMA-%B) were calculated in
      each subject using homeostasis model assessment (HOMA). Rosglitazone improved the
      overall glycemic control in the IGT and DM groups. Following rosiglitazone, the
      beta-cell secretion remained unchanged, while HOMR-IR was reduced in DM by 30%
      (4.12 +/- 1.95 v 6.33 +/- 3.54, P < .05) and the IGT group (3.78 +/- 2.45 v 4.81
      +/- 3.49, P = not significant [NS]). Mean plasma adiponectin levels were
      significantly (P < .05) lower in the DM (6.74 +/- 1.95 microg/mL) when compared
      with the NGT group(9.61 +/- 5.09). Rosiglitazone significantly (P < .001)
      increased adiponectin levels by 2-fold in patients with IGT (22.2 +/- 10.97
      microg/mL) and 2.5-fold greater in DM (15.68 +/- 8.23 microg/mL) at 3 months when
      compared with the 0 month. We conclude that adiponectin could play a significant
      role (1) in the pathogenesis of IGT and DM and (2) the beneficial metabolic
      effects of thiazolidinediones (TZDs) in high-risk African American patients.

PMID- 15562400
TI  - Partial leptin restoration increases hypothalamic-pituitary-adrenal activity
      while diminishing weight loss and hyperphagia in streptozotocin diabetic rats.
AB  - Chronic leptin administration at pharmacologic doses normalizes food intake and
      body weight in streptozotocin (STZ)-diabetic rats. We examined the metabolic
      effects of acute partial physiological leptin restoration in STZ-diabetic rats by
      using subcutaneous osmotic mini pumps. Groups: (1) Rats infused with vehicle
      (DV); (2) rats infused with recombinant murine methionine leptin (DL) at 4.5
      microg . (kg body weight . d)(-1); (3)pair-fed rats (DP) given a food ration
      matching that consumed by the DL group. A fourth group of nondiabetic, normal (N)
      rats was also studied to assess normal metabolic efficiency, hypothalamic
      pituitary-adrenal (HPA) activity and sympathoadrenal activity. Following leptin
      infusion, food consumption by DL rats was significantly lower than in DV rats.
      Paradoxically, despite a similar food intake to that of the DP group, which
      demonstrated a 40% reduction in body mass, DL rats increased their initial body
      weight by approximately 20% (P < .05). Plasma corticosterone and ACTH
      concentrations were elevated by 2-fold to 3-fold in DL versus N, DP, and DV rats.
      In the pars distalis, glucocorticoid receptor (GR) mRNA levels were significantly
      higher in DL and DP rats compared with N and DV rats. Our results suggest that
      partial restoration of physiologic leptin: (1) successfully reduces hyperphagia
      while allowing body weight gain in STZ-diabetic rats; (2) increases
      corticosterone levels in STZ-diabetic rats, which may in turn counteract the
      anorexic effects of diabetes; and (3) is associated with increased pituitary GR
      mRNA levels, despite elevated corticosterone levels, suggesting that leptin may
      interfere with the negative feedback regulation of the HPA axis.

PMID- 15562401
TI  - Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin
      like growth factor-binding protein-3 protease, and growth hormone-binding protein
      in lipodystrophic human immunodeficiency virus-infected patients.
AB  - Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired
      growth hormone (GH) secretion. It remains to be elucidated whether insulin-like
      growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH
      binding protein (GHBP) are abnormal in HIV-lipodystrophy. These parameters were
      measured in overnight fasting serum samples from 16 Caucasian males with HIV
      lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy
      (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral
      therapy. In LIPO, abdominal fat mass and insulin concentration were increased
      (>90%, P < .01) and insulin sensitivity (Log10ISI(composite)) was decreased (
      50%, P < .001). Total and free IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease were
      similar between groups (all P > .5), whereas, in LIPO, IGFBP-1 and IGFBP-2 were
      reduced (-36%, P < .05 and -50%, P < .01). In pooled groups, total IGF-I, free
      IGF-I, total IGF-II, and IGFBP-3, respectively, correlated inversely with age
      (all P < .01). In pooled groups, IGFBP-1 and IGFBP-2 correlated positively with
      insulin sensitivity (age-adjusted all P < .05). IGFBP-3 protease correlated with
      free IGF-I in pooled groups (r(p) = 0.47, P < .02), and in LIPO (r(p) = 0.71, P <
      .007) controlling for age, total IGF-I, and IGFBP-3. GHBP was increased, whereas
      GH was decreased in LIPO (all P < .05). GH correlated inversely with GHBP in
      pooled groups (P < .05). Taken together the similar IGFs and IGFBP-3
      concentrations between study groups, including suppressed GH, and increased GHBP
      in LIPO, argue against GH resistance of GH-sensitive tissues in LIPO compared
      with NONLIPO; however, this notion awaits examination in dose-response studies.
      Furthermore, our data suggest that IGFBP-3 protease is a significant regulator of
      bioactive IGF-I in HIV-lipodystrophy.

PMID- 15562402
TI  - Relationship between obesity, smoking, and the endogenous nitric oxide synthase
      inhibitor, asymmetric dimethylarginine.
AB  - We investigated the levels of asymmetric dimethylarginine (ADMA), an important
      endogenous inhibitor of nitric oxide (NO), as related to metabolic risk factors
      known to contribute to atherosclerotic disease. Dimethylarginines were analysed
      in a cross-sectional study of 563 elderly high-risk men (70 +/- 6 years). ADMA
      and the l-arginine/ADMA (l-arg/ADMA) ratio were highly significantly correlated
      with several metabolic risk factors. However, only the association with body mass
      index (BMI) remained significant after adjustment for inter-related variables.
      When analyzing the results according to being overweight or not, ADMA levels were
      independently significantly higher (P = .05) and the L-arg/ADMA ratios were
      significantly lower (P < .008) in individuals with high BMI (> or =26 kg/m(2),
      median value) as compared with subjects with low BMI. ADMA levels were
      furthermore significantly lower (P = .037) and L-arginine and the l-arg/ADMA
      ratios were significantly higher (P = .004 and P = .001, respectively) in smokers
      compared with nonsmokers, the latter being independent of other risk factors. The
      strong relationship found between BMI and plasma levels of ADMA and the l
      arg/ADMA ratio indicate a link to endothelial dysfunction in overweight subjects.
      The beneficial dimethylarginine profile observed in smokers in this elderly
      population is not easily explainable and should be further investigated.

PMID- 15562403
TI  - A general method for the synthesis of bastaranes and isobastaranes: first total
      synthesis of bastadins 5, 10, 12, 16, 20, and 21.
AB  - A general strategy for the synthesis of twenty naturally occurring bastadins (all
      but bastadin 3) is presented. A key retrosynthetic disconnection of the two amide
      bonds, common in all target molecules, bisects the macrocyclic core into two
      diaryl ether fragments, an alpha,omega-diamine (western part) and an alpha,omega
      dicarboxylic acid (eastern part). Efficient preparation of the synthetically
      challenging o-mono or dibromo-substituted diaryl ether linkages was achieved
      employing the diaryl iodonium salt method. Regarding the western part, variations
      of the aliphatic chain were more efficiently secured by the preparation of two
      different alpha,omega-aminonitrile moieties. Cobalt boride mediated reduction of
      the nitrile functionality established the required diamines and, at the same
      time, provided the necessary variation of the aromatic-ring bromination pattern.
      Regarding the eastern part, two different dicarboxyl precursors had to be
      prepared in order to accommodate bromination-pattern variations. Coupling and
      subsequent macrolactamization of different combinations of these key
      intermediates may lead at will to any member of this family of marine natural
      products. Four bastaranes (bastadins 5, 10, 12 and 16) and two isobastaranes
      (bastadins 20 and 21) were synthesized as a demonstration of the flexibility and
      efficiency of the approach presented.

PMID- 15562404
TI  - The role of physical environment on molecular electromechanical switching.
AB  - The influences of different physical environments on the thermodynamics
      associated with one key step in the switching mechanism for a pair of bistable
      catenanes and a pair of bistable rotaxanes have been investigated systematically.
      The two bistable catenanes are comprised of a cyclobis(paraquat-p-phenylene)
      (CBPQT4+) ring, or its diazapyrenium-containing analogue, that are interlocked
      with a macrocyclic polyether component that incorporates the strong
      tetrathiafulvalene (TTF) donor unit and the weaker 1,5-dioxynaphthalene (DNP)
      donor unit. The two bistable rotaxanes are comprised of a CBPQT4+ ring,
      interlocked with a dumbbell component in which one incorporates TTF and DNP
      units, whereas the other incorporates a monopyrrolotetrathiafulvalene (MPTTF)
      donor and a DNP unit. Two consecutive cycles of a variable scan rate cyclic
      voltammogram (10-1500 mV s(-1)) performed on all of the bistable switches
      (approximately 1 mM) in MeCN electrolyte solutions (0.1 M tetrabutylammonium
      hexafluorophosphate) across a range of temperatures (258-303 K) were recorded in
      a temperature-controlled electrochemical cell. The second cycle showed different
      intensities of the two features that were observed in the first cycle when the
      cyclic voltammetry was recorded at fast scan rates and low temperatures. The
      first oxidation peak increases in intensity, concomitant with a decrease in the
      intensity of the second oxidation peak. This variation changed systematically
      with scan rate and temperature and has been assigned to the molecular mechanical
      movements within the catenanes and rotaxanes of the CBPQT4+ ring from the DNP to
      the TTF unit. The intensities of each peak were assigned to the populations of
      each co-conformation, and the scan-rate variation of each population was analyzed
      to obtain kinetic and thermodynamic data for the movement of the CBPQT4+ ring.
      The Gibbs free energy of activation at 298 K for the thermally activated movement
      was calculated to be 16.2 kcal mol(-1) for the rotaxane, and 16.7 and 19.2 kcal
      mol(-1) for the bipyridinium- and diazapyrenium-based bistable catenanes,
      respectively. These values differ from those obtained for the shuttling and
      circumrotational motions of degenerate rotaxanes and catenanes, respectively,
      indicating that the detailed chemical structure influences the rates of movement.
      In all cases, when the same bistable compounds were characterized in an
      electrolyte gel, the molecular mechanical motion slowed down significantly,
      concomitant with an increase in the activation barriers by more than 2 kcal mol(
      1). Irrespective of the environment--solution, self-assembled monolayer or solid
      state polymer gel--and of the molecular structure--rotaxane or catenane--a single
      and generic switching mechanism is observed for all bistable molecules.

PMID- 15562405
TI  - Increased blood-brain barrier permeability with thymidine phosphorylase
      deficiency.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive
      multisystemic disorder caused by thymidine phosphorylase deficiency. Whereas the
      pathomechanism of the secondary mitochondrial dysfunction has been extensively
      studied, that of the leukoencephalopathy has not been elucidated. We hypothesized
      that the white matter hyperintensities on T2-weighted magnetic resonance images
      reflect disturbance of blood-brain barrier function. Albumin immunohistochemistry
      disclosed quantitative (p < 0.01) and qualitative differences between the
      mitochondrial neurogastrointestinal encephalomyopathy and control brains,
      indicating that loss of thymidine phosphorylase function impairs the integrity of
      the blood-brain barrier.

PMID- 15562406
TI  - Verbal selective learning after traumatic brain injury in children.
AB  - Selective learning (SL), the ability to select items to learn from among other
      items, engages cognitive control, which is purportedly mediated by the frontal
      cortex and its circuitry. Using incentive-based auditory word recall and
      expository discourse tasks, we studied the efficiency of SL in children ages 6 to
      16 years who had sustained severe traumatic brain injury (TBI) at least 1 year
      earlier. We hypothesized that SL would be compromised by severe TBI. Results
      indicated that children with severe TBI performed significantly worse than age
      matched typically developing children on word- and discourse-level measures of SL
      efficiency with no significant group differences in number of items recalled from
      auditory word lists or declarative facts. We conclude that severe TBI disrupts
      incentive-based cognitive control processes, possibly due to involvement of
      frontal neural networks.

PMID- 15562408
TI  - Friedreich ataxia in carriers of unstable borderline GAA triplet-repeat alleles.
AB  - Friedreich ataxia patients are homozygous for expanded GAA triplet-repeats
      containing 66 to 1,700 triplets. We report two patients with delayed-onset,
      hyperreflexia and gradually progressive disease. Both were heterozygous for large
      expansions and also carried alleles with 44 and 66 triplet-repeats, respectively.
      Due to somatic instability, 15% (GAA-44) and 75% (GAA-66) of cells contained
      alleles with >/=66 triplet-repeats, constituting a plausible mechanism for their
      mild phenotype. A sibling with a stable GAA-37 allele and a large expansion was
      clinically normal. Instability of borderline alleles confers a risk for
      Friedreich ataxia, and the range of pathogenic alleles is broader than previously
      recognized.

PMID- 15562409
TI  - Reorganization in congenital hemiparesis acquired at different gestational ages.
AB  - It is well established that the reorganizational potential of the developing
      human brain is superior to that of the adult brain, but whether age-dependent
      differences exist already in the prenatal and perinatal period is not known. We
      have studied sensorimotor reorganization in 34 patients with congenital
      hemiparesis (age range, 5-27 years), using transcranial magnetic stimulation and
      functional magnetic resonance imaging during simple hand movements. Underlying
      pathologies were brain malformations (first and second trimester lesions; n =
      10), periventricular brain lesions (early third trimester lesions; n = 12), and
      middle cerebral artery infarctions (late third trimester lesions; n = 12). Of
      this cohort, eight patients with malformations and all patients with
      periventricular lesions have been published previously. In all three groups of
      pathologies, transcranial magnetic stimulation identified patients in whom the
      paretic hand was controlled via ipsilateral corticospinal projections from the
      contralesional hemisphere (n = 16). In these patients, the motor dysfunction of
      the paretic hand correlated significantly with the timing period of the
      underlying brain lesion. This demonstrates that the efficacy of reorganization
      with ipsilateral corticospinal tracts indeed decreases during pregnancy.

PMID- 15562411
TI  - Astrocyte specific viral strains in HIV dementia.
AB  - We molecularly characterized human immunodeficiency virus type 1 (HIV-1) present
      in pure populations of astrocytes, macrophages, and multinucleated giant cells
      isolated using laser capture microdissection from brain tissue of two patients
      who died with HIV-associated dementia. The V3 region of the HIV-1 envelope (env)
      gene was amplified from the pure-cell populations, and multiple clones were
      sequenced. In both patients, the V3 env sequences were distinct in astrocytes
      compared with neighboring macrophages or multinucleated giant cells and were
      characteristic of CCR5-using (R5) HIV-1. These results demonstrate cell-specific
      compartmentalization of distinct R5-like viral strains in the central nervous
      system microenvironment.

PMID- 15562412
TI  - Beneficial effect of erythropoietin on experimental allergic encephalomyelitis.
AB  - We have known for a long time that erythropoietin signaling plays a key role in
      bone marrow erythrocyte proliferation. However, recent studies have indicated
      that erythropoietin also may have protective effects on the nervous system. This
      unexpected role remains incompletely characterized. To investigate the potential
      neuroprotective role of erythropoietin in the central nervous system, we assessed
      its effects on a well-characterized autoimmune demyelinating model of multiple
      sclerosis-myelin oligodendrocyte glycoprotein-induced experimental autoimmune
      encephalomyelitis (EAE) in the mouse. We found that erythropoietin administered
      intravenously for 14 days after the onset of symptoms reduced both disease
      severity and duration of maximum impairment at dose levels as low as 50U/kg (p <
      0.001). We assessed the neuropathology of diseased spinal cords and found that
      erythropoietin-treated EAE animals had reduced axonal damage, inflammatory cell
      infiltration and demyelination, and diminished blood-brain barrier leakage when
      compared with saline-treated EAE controls. Moreover, the pronounced upregulation
      of spinal cord major histocompatibility complex (MHC) class II expression found
      in saline-treated EAE was significantly reduced in erythropoietin-treated
      animals, a finding we replicated in vitro, using microglial cultures. The notion
      that short-term erythropoietin therapy might be of clinical benefit in human
      autoimmune demyelinating diseases needs investigation.

PMID- 15562413
TI  - Learning to read without a left occipital lobe: right-hemispheric shift of visual
      word form area.
AB  - Using anatomical and functional magnetic resonance imaging, we studied the
      pattern of brain lateralization during spoken and written language tasks, in an
      11-year-old girl who underwent a left occipitotemporal resection for a Sturge
      Weber angioma at the age of 4 years, that is, after the development of speech but
      before the acquisition of reading. We observed a selective and successful shift
      to the right hemisphere of the visual component of reading, particularly the
      Visual Word Form Area, whereas the verbal components remained strongly left
      lateralized. This emphasizes the potential utility of a precise functional and
      developmental cartography of language for the surgical treatment of focal brain
      lesions in children.

PMID- 15562414
TI  - Selective loss of regulatory T cells in thymomas.
AB  - Myasthenia gravis (MG) is the prime autoimmune manifestation of thymomas. We
      investigated the generation of T cells with a regulatory phenotype (T(R)) in
      thymomas with and without associated MG. In patients with MG(+) thymomas,
      maturation and export of T(R) cells but not of other T-cell subsets was
      significantly reduced. We conclude that imbalance between effector and regulatory
      T cells in thymomas may be involved in modulation of onset and/or severity of MG.

PMID- 15562415
TI  - Successful management of cataplexy with intravenous immunoglobulins at narcolepsy
      onset.
AB  - Hypocretin/orexin deficiency appears to be a consistent feature of narcolepsy
      with a putative autoimmune mechanism involved. We treated four hypocretin/orexin
      deficient narcolepsy patients with intravenous immunoglobulins and assessed the
      efficacy by repeated polysomnographies and questionnaires. Three patients
      received the treatment within a few months after acute onset of narcolepsy. A
      clear improvement in the frequency and severity of cataplexy was obtained with a
      benefic effect up to 7 months without any anticataplectics drugs at follow-up.
      Our findings point to the importance of early diagnosis of narcolepsy, which once
      treated quickly may modify its long-term outlook.

PMID- 15562417
TI  - Versatile self-complexing compounds based on covalently linked donor-acceptor
      cyclophanes.
AB  - A range of covalently linked donor-acceptor compounds which contain 1) a
      hydroquinone (HQ) unit, 2) a 1,5-dioxynaphthalene (DNP) ring system, or 3) a
      tetrathiafulvalene (TTF) unit as the pi-donor, and 4) cyclobis(paraquat-p
      phenylene) (CBPQT(4+)) as the pi-accepting tetracationic cyclophane were prepared
      and shown to operate as simple molecular machines. The pi-donating arms can be
      included inside the cyclophane in an intramolecular fashion by virtue of
      stabilizing noncovalent bonding interactions. What amounts to self
      complexing/decomplexing equilibria were shown to be highly temperature dependent
      when the pi-donating arm contains either an HQ or DNP moiety. The thermodynamic
      parameters associated with the equilibria have been unraveled by using variable
      temperature (1)H NMR spectroscopy. The negative DeltaH degrees and DeltaS degrees
      values account for the fact that the "uncomplexed" conformation becomes the
      dominant species, since the entropy gain associated with the decomplexation
      process overcomes the enthalpy loss resulting from the breaking of the donor
      acceptor interactions. The arm's in-and-out movements with respect to the linked
      cyclophanes can be arrested by installing a bulky substituent at the end of the
      arm. In the case of compounds carrying a DNP ring system in their side arm, two
      diastereoisomeric, self-complexing conformations are observed below 272 K in
      hexadeuterioacetone. By contrast, control over the TTF-containing arm's movement
      is more or less ineffective through the thermally sensitive equilibrium although
      it can be realized by chemical and electrochemical ways as a result of TTF's
      excellent redox properties. Such self-complexing compounds could find
      applications as thermo- and electroswitches. In addition, the thermochromism
      associated with the arm's movement could lead to some of the compounds finding
      uses as imaging and sensing materials.

PMID- 15562418
TI  - Medical errors: the perspective of the insurer.
AB  - Errors in medicine have a significant impact upon the cost of health insurance in
      the United States. These errors may reflect a range of errors ranging from
      ineffective or futile care to inappropriate medical judgments to coding errors.
      These may be unintentional, but underlying all of these error-types is a failure
      of process stemming back to physician training. The commercial industries that
      pay for health insurance may be demanding a process approach and accountability
      structures in return for continued funding of health care services.

PMID- 15562425
TI  - Bilateral limbic diffusion abnormalities in unilateral temporal lobe epilepsy.
AB  - Diffusion tensor magnetic resonance imaging can acquire quantitative information
      on the microstructural integrity of white matter structures and depict brain
      connectivity in vivo based on the behavior of water diffusion. Diffusion tensor
      imaging-derived tractography has been used for virtual dissection of the fornix
      and cingulum in healthy subjects, but not in patients with temporal lobe epilepsy
      (TLE). Eight patients with medically intractable TLE and unilateral mesial
      temporal sclerosis and nine healthy control subjects were imaged using diffusion
      tensor imaging. Fiber tracking was performed to delineate the fornix and
      cingulum, which were quantitatively analyzed. Bilateral symmetrical reduction in
      fractional anisotropy was observed in the fornix of patients with TLE, together
      with an increase in water mobility perpendicular to the axis of the fibers. The
      findings in the cingulum are similar to those of the fornix with the exception of
      significantly increased bulk diffusivity in the latter. We observed strikingly
      symmetrical bilateral abnormalities of axonal integrity in the fornix and
      cingulum in a series of patients with unilateral mesial temporal sclerosis. Our
      findings suggest that TLE with unilateral mesial temporal sclerosis is associated
      with bilateral limbic system pathology.

PMID- 15562426
TI  - Joint multi-population analysis for genetic linkage of bipolar disorder or
      "wellness" to chromosome 4p.
AB  - To test the hypothesis that the same genetic loci confer susceptibility to, or
      protection from, disease in different populations, and that a combined analysis
      would improve the map resolution of a common susceptibility locus, we analyzed
      data from three studies that had reported linkage to bipolar disorder in a small
      region on chromosome 4p. Data sets comprised phenotypic information and genetic
      marker data on Scottish, Danish, and USA extended pedigrees. Across the three
      data sets, 913 individuals appeared in the pedigrees, 462 were classified, either
      as unaffected (323) or affected (139) with unipolar or bipolar disorder. A
      consensus linkage map was created from 14 microsatellite markers in a 33 cM
      region. Phenotypic and genetic data were analyzed using a variance component (VC)
      and allele sharing method. All previously reported elevated test statistics in
      the region were confirmed with one or both analysis methods, indicating the
      presence of one or more susceptibility genes to bipolar disorder in the three
      populations in the studied chromosome segment. When the results from both the VC
      and allele sharing method were considered, there was strong evidence for a
      susceptibility locus in the data from Scotland, some evidence in the data from
      Denmark and relatively less evidence in the data from the USA. The test
      statistics from the Scottish data set dominated the test statistics from the
      other studies, and no improved map resolution for a putative genetic locus
      underlying susceptibility in all three studies was obtained. Studies reporting
      linkage to the same region require careful scrutiny and preferably joint or meta
      analysis on the same basis in order to ensure that the results are truly
      comparable.

PMID- 15562428
TI  - High tumor necrosis factor-alpha [corrected] levels in cerebrospinal fluid of
      cobalamin-deficient patients.
AB  - We studied 14 patients with neurological manifestations of subacute combined
      degeneration (SCD) and 40 control patients not cobalamin (Cbl)-deficient. The
      cerebrospinal fluid (CSF) markers of Cbl deficiency (Cbl and total homocysteine
      [tHCYS] levels) and the CSF levels of tumor necrosis factor (TNF)-alpha and
      epidermal growth factor (EGF) were measured. Significantly higher levels of tHCYS
      and TNF-alpha, and significantly lower levels of Cbl and EGF were found in the
      SCD patients. In human CSF, as in human serum and the rat central nervous system,
      decreased Cbl concentrations are concomitant with an increase in TNF-alpha and a
      decrease in EGF-levels. Ann Neurol 2004;56:886-890.

PMID- 15562429
TI  - In vivo detection of microglial activation in frontotemporal dementia.
AB  - Using positron emission tomography and [(11)C](R)-PK11195, a marker of
      "peripheral benzodiazepine sites" that is upregulated on activated microglia
      during progressive tissue pathology, we show increased binding of [(11)C](R)
      PK11195 in frontotemporal lobar degeneration in the typically affected
      frontotemporal brain regions. This implies the presence of an active glial
      response reflecting progressive neuronal degeneration. It also suggests that
      increased [(11)C](R)-PK11195 binding, previously demonstrated for Alzheimer's
      disease, may occur independently from increased amyloid plaque formation, given
      that it is not a characteristic feature of frontotemporal lobar degeneration.

PMID- 15562430
TI  - Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis
      type 1, and Down's syndrome.
AB  - Blood gene expression profiling has been applied to a variety of hematological
      malignancies, autoimmune disorders, and infectious diseases. This study applies
      this approach to genetic diseases without obvious blood phenotypes. Three genetic
      diseases including tuberous sclerosis complex 2, neurofibromatosis type 1, and
      Down's syndrome were compared with a group of healthy controls. RNA from whole
      blood was surveyed using Affymetrix U133A arrays. Each disease was associated
      with a unique gene expression pattern in blood that can be accurately
      distinguished by a classifier. Genes on chromosome 21 were overexpressed in
      Down's syndrome, and genes controlling cell cycle and proliferation were
      associated with tuberous sclerosis complex type 2 or neurofibromatosis type 1. A
      subset of genes involved in cardiac development or remodeling were overexpressed
      in patients with Down's syndrome and congenital heart defects. These findings
      suggest that blood gene expression profiling on a broader basis might be useful
      for genetic disease screening/diagnosis and might help elucidate mechanisms and
      pathways that lead to genotype-phenotype differences.

PMID- 15562431
TI  - Hypoperfusion without stroke alters motor activation in the opposite hemisphere.
AB  - To specifically investigate the effect that large-vessel disease may have on
      cortical reorganization, we used functional magnetic resonance imaging to study
      patients with unilateral hemispheric hypoperfusion and impaired vasomotor
      reactivity from critical internal carotid or middle cerebral artery disease but
      without stroke. We hypothesized that when these patients used the hand
      contralateral to the hypoperfused hemisphere they would show unique activation in
      motor-related areas of the normally perfused hemisphere, that is, ipsilateral
      activation. We found that normal performance of two motor tasks was associated
      with increased ipsilateral hemispheric activation in the patients compared with
      age-matched controls. In addition, although task difficulty had an effect on
      ipsilateral activation, the increased ipsilateral activation seen in patients was
      not dependent on task difficulty. Our findings demonstrate that hemodynamic
      compromise alone is sufficient to cause atypical ipsilateral activation. This
      activation may serve to maintain normal motor performance.

PMID- 15562433
TI  - Brain lumps and bumps: a neural risk for autism.

PMID- 15562434
TI  - Striking PrPsc heterogeneity in inherited prion diseases with the D178N mutation.

PMID- 15562437
TI  - NAD+ as a metabolic link between DNA damage and cell death.
AB  - DNA damage occurs in ischemia, excitotoxicity, inflammation, and other disorders
      that affect the central nervous system (CNS). Extensive DNA damage triggers cell
      death and in the mature CNS, this occurs primarily through activation of the
      poly(ADP-ribose) polymerase-1 (PARP-1) cell death pathway. PARP-1 is an abundant
      nuclear enzyme that, when activated by DNA damage, consumes nicotinamide adenine
      dinucleotide (NAD)+ to form poly(ADP-ribose) on acceptor proteins. The mechanisms
      by which PARP-1 activation leads to cell death are not understood fully. We used
      mouse astrocyte cultures to explore the bioenergetic effects of NAD+ depletion by
      PARP-1 and the role of NAD+ depletion in this cell death program. PARP-1
      activation was induced by the DNA alkylating agent, N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), using medium in which glucose was the only exogenous
      energy substrate. PARP-1 activation led to a rapid but incomplete depletion of
      astrocyte NAD+, a near-complete block in glycolysis, and eventual cell death.
      Repletion of intracellular NAD+ restored glycolytic function and prevented cell
      death. The addition of non-glucose substrates to the medium, pyruvate, glutamate,
      or glutamine, also prevented astrocyte death after PARP-1 activation. These
      studies suggest PARP-1 activation leads to rapid depletion of the cytosolic but
      not the mitochondrial NAD+ pool. Depletion of the cytosolic NAD+ pool renders the
      cells unable to utilize glucose as a metabolic substrate. Under conditions where
      glucose is the only available metabolic substrate, this leads to cell death. This
      cell death pathway is particularly germane to brain because glucose is normally
      the only metabolic substrate that is transported rapidly across the blood-brain
      barrier.

PMID- 15562436
TI  - Pyruvate dehydrogenase complex: metabolic link to ischemic brain injury and
      target of oxidative stress.
AB  - The mammalian pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix
      enzyme complex (greater than 7 million Daltons) that catalyzes the oxidative
      decarboxylation of pyruvate to form acetyl CoA, nicotinamide adenine dinucleotide
      (the reduced form, NADH), and CO(2). This reaction constitutes the bridge between
      anaerobic and aerobic cerebral energy metabolism. PDHC enzyme activity and
      immunoreactivity are lost in selectively vulnerable neurons after cerebral
      ischemia and reperfusion. Evidence from experiments carried out in vitro suggests
      that reperfusion-dependent loss of activity is caused by oxidative protein
      modifications. Impaired enzyme activity may explain the reduced cerebral glucose
      and oxygen consumption that occurs after cerebral ischemia. This hypothesis is
      supported by the hyperoxidation of mitochondrial electron transport chain
      components and NAD(H) that occurs during reperfusion, indicating that NADH
      production, rather than utilization, is rate limiting. Additional support comes
      from the findings that immediate postischemic administration of acetyl-L
      carnitine both reduces brain lactate/pyruvate ratios and improves neurologic
      outcome after cardiac arrest in animals. As acetyl-L-carnitine is converted to
      acetyl CoA, the product of the PDHC reaction, it follows that impaired production
      of NADH is due to reduced activity of either PDHC or one or more steps in
      glycolysis. Impaired cerebral energy metabolism and PDHC activity are associated
      also with neurodegenerative disorders including Alzheimer's disease and Wernicke
      Korsakoff syndrome, suggesting that this enzyme is an important link in the
      pathophysiology of both acute brain injury and chronic neurodegeneration.

PMID- 15562438
TI  - Futile cycling of lactate through the plasma membrane of C6 glioma cells as
      detected by (13C, 2H) NMR.
AB  - We report a novel ((13)C, (2)H) nuclear magnetic resonance (NMR) procedure to
      investigate lactate recycling through the monocarboxylate transporter of the
      plasma membrane of cells in culture. C6 glioma cells were incubated with [3
      (13)C]lactate in Krebs-Henseleit Buffer containing 50% (2)H(2)O (vol/vol) for up
      to 30 hr. (13)C NMR analysis of aliquots progressively taken from the medium,
      showed: (1) a linearly decreasing singlet at approximately 20.85 parts per
      million (ppm; -0.119 micromol/mg protein/hr) derived from the methyl carbon of [3
      (13)C]lactate; and (2) an exponentially increasing shifted singlet at
      approximately 20.74 ppm (0.227 micromol/ mg protein/hr) from the methyl carbon of
      [3-(13)C, 2-(2)H]lactate. The shifted singlet appears because during its transit
      through the cytosol, [3-(13)C]lactate generates [3-(13)C, 2-(2)H]lactate in the
      lactate dehydrogenase (LDH) equilibrium, which may return to the incubation
      medium through the reversible monocarboxylate carrier. The methyl group of [3
      (13)C, 2-(2)H]lactate is shifted -0.11 ppm with respect to that of [3
      (13)C]lactate, making it possible to distinguish between both molecules by (13)C
      NMR. During incubations with 2.5 mM [1-(13)C]glucose and 3.98 mM [U
      (13)C(3)]lactate or with 2.5 mM [1-(13)C]glucose and 3.93 mM [2-(13)C]pyruvate,
      C2-deuterated lactate was produced only from [1-(13)C]glucose or [U
      (13)C(3)]lactate, revealing that this deuteration process is redox sensitive.
      When [1-(13)C]glucose and [U-(13)C(3)]lactate were used as substrates, no
      significant [3-(13)C]lactate production from [1-(13)C]glucose was detected,
      suggesting that glycolytic lactate production may be stopped under the high
      lactate concentrations prevailing under mild hypoxic or ischemic episodes or
      during cerebral activation.

PMID- 15562439
TI  - Pentylenetetrazole affects metabolism of astrocytes in culture.
AB  - Cortical and cerebellar astrocytes were cultured in medium containing
      pentylenetetrazole (PTZ), a gamma-aminobutyric acid (GABA)(A) receptor
      antagonist, for 3 weeks (up to 6 mM) or 2 hr (10 mM). Cells were incubated in
      medium containing [U-(13)C]glutamate (0.5 mM) and unlabeled glucose (3 mM) for 2
      hr and cell extracts and media were analyzed by (13)C magnetic resonance (MR)
      spectroscopy and high-performance liquid chromatography (HPLC). When cerebellar
      astrocytes were incubated with PTZ for 2 hr, the amount of glucose removed from
      the medium and glucose and [U-(13)C]glutamate oxidation were decreased.
      Metabolism in cortical astrocytes was affected only slightly; amounts of
      glutathione and aspartate were decreased. When cerebellar and cortical cells were
      cultured in the presence of PTZ for 3 weeks, the amount of glucose removed from
      the medium and lactate formed were increased, indicating increased glycolytic
      activity. Despite the increased intracellular [U-(13)C]glutamate concentration in
      both types of astrocytes cultured with PTZ, labeled glutamine and glutathione
      were unchanged, indicating intracellular compartmentation. The amount of cellular
      protein was decreased at 6 mM PTZ for cerebellar astrocytes and 1 mM for cortical
      astrocytes, indicating a differential sensitivity to the effects of PTZ. In
      conclusion, mitochondrial metabolism and glycolysis were decreased by short-term
      incubation with PTZ in cerebellar astrocytes, whereas long-term incubation
      affected both types of astrocytes, leading to increased glycolysis.

PMID- 15562440
TI  - In vitro hepatic differentiation of human mesenchymal stem cells.
AB  - This study examined whether mesenchymal stem cells (MSCs), which are stem cells
      originated from embryonic mesoderm, are able to differentiate into functional
      hepatocyte-like cells in vitro. MSCs were isolated from human bone marrow and
      umbilical cord blood, and the surface phenotype and the mesodermal multilineage
      differentiation potentials of these cells were characterized and tested. To
      effectively induce hepatic differentiation, we designed a novel 2-step protocol
      with the use of hepatocyte growth factor and oncostatin M. After 4 weeks of
      induction, cuboidal morphology, which is characteristic of hepatocytes, was
      observed, and cells also expressed marker genes specific of liver cells in a time
      dependent manner. Differentiated cells further demonstrated in vitro functions
      characteristic of liver cells, including albumin production, glycogen storage,
      urea secretion, uptake of low-density lipoprotein, and phenobarbital-inducible
      cytochrome P450 activity. In conclusion, human MSCs from different sources are
      able to differentiate into functional hepatocyte-like cells and, hence, may serve
      as a cell source for tissue engineering and cell therapy of hepatic tissues.
      Furthermore, the broad differentiation potential of MSCs indicates that a
      revision of the definition may be required.

PMID- 15562441
TI  - Transcription factor HNF-6/OC-1 inhibits the stimulation of the HNF-3alpha/Foxa1
      gene by TGF-beta in mouse liver.
AB  - A network of liver-enriched transcription factors controls differentiation and
      morphogenesis of the liver. These factors interact via direct, feedback, and
      autoregulatory loops. Previous work has suggested that hepatocyte nuclear factor
      (HNF)-6/OC-1 and HNF-3alpha/FoxA1 participate coordinately in this hepatic
      network. We investigated how HNF-6 controls the expression of Foxa1. We observed
      that Foxa1 expression was upregulated in the liver of Hnf6(-/-) mouse embryos and
      in bipotential mouse embryonic liver (BMEL) cell lines derived from embryonic
      Hnf6(-/-) liver, suggesting that HNF-6 inhibits the expression of Foxa1. Because
      no evidence for a direct repression of Foxa1 by HNF-6 was found, we postulated
      the existence of an indirect mechanism. We found that the expression of a
      mediator and targets of the transforming growth factor beta (TGF-beta) signaling
      was increased both in Hnf6(-/-) liver and in Hnf6(-/-) BMEL cell lines. Using
      these cell lines, we demonstrated that TGF-beta signaling was increased in the
      absence of HNF-6, and that this resulted from upregulation of TGF-beta receptor
      II expression. We also found that TGF-beta can stimulate the expression of Foxa1
      in Hnf6(+/+) cells and that inhibition of TGF-beta signaling in Hnf6(-/-) cells
      down-regulates the expression of Foxa1. In conclusion, we propose that Foxa1
      upregulation in the absence of HNF-6 results from increased TGF-beta signaling
      via increased expression of the TGF-beta receptor II. We further conclude that
      HNF-6 inhibits Foxa1 by inhibiting the activity of the TGF-beta signaling
      pathway. This identifies a new mechanism of interaction between liver-enriched
      transcription factors whereby one factor indirectly controls another by
      modulating the activity of a signaling pathway.

PMID- 15562442
TI  - Application of a novel quadrupole linear ion trap mass spectrometer to study the
      metabolism of 6-aminobutylphthalide in rat brains.

PMID- 15562443
TI  - Determination of iron in calcium-rich samples by tungsten boat furnace
      vaporization with inductively coupled plasma mass spectrometry using calcium(II)
      ion as a chemical modifier.

PMID- 15562444
TI  - Electron ionization mass spectrometric study of 1,4-dihydro-4-substituted 2,6
      dimethyl-3,5-bis(alkoxycarbonyl)pyridines.
AB  - Using the accurate masses obtained from a time-of-flight instrument and the
      tandem mass spectrometric (MS/MS) data from an ion trap instrument, electron
      ionization mass spectra of a series of 1,4-dihydro-4-substituted 2,6-dimethyl-3,5
      bis(alkoxycarbonyl)pyridines are reported and rationalized. Two sets of
      fragmentation pathways are proposed. One involves the formation of fragment ions
      containing the 1,4-dihydropyridine structure, and the other of ions containing a
      pyridine ring.

PMID- 15562445
TI  - Coupling of fully automated chip electrospray to Fourier transform ion cyclotron
      resonance mass spectrometry for high-performance glycoscreening and sequencing.
AB  - The NanoMate robot has been coupled to a Fourier transform ion cyclotron
      resonance (FTICR) mass spectrometer at 9.4 T and implemented for the first time
      for complex carbohydrate analysis. It was optimized in the negative ion mode to
      achieve automated sample delivery on the chip along with increased sensitivity,
      ultra-high resolution and accurate mass determination. A novel bracket has been
      designed to allow a reliable mounting of the NanoMate to the Apollo electrospray
      ionization (ESI) source of an APEX II instrument. The notably higher efficiency
      of ionization for compositional mapping of complex mixtures and feasibility for
      fragmentation analysis of components by sustained off-resonance irradiation
      collision-induced tandem mass spectrometry (SORI-CID MS2) has been demonstrated
      on a glycoconjugate mixture containing O-glycosylated sialylated peptides from
      urine of a patient suffering from a hereditary N-acetylhexosaminidase deficiency
      (Schindler's disease), previously analyzed by capillary-based nanoESI-FTICRMS,
      and of a healthy control person. Due to its potential to generate highly charged
      ionic species, reduce the in-source fragmentation, increase sensitivity,
      reproducibility and ionization efficiency, along with the ability to generate a
      sustained and constant electrospray, this method can be considered as a new
      platform for advanced glycomics.

PMID- 15562446
TI  - Carbohydrate metabolism in the central nervous system of the megalobulimus
      oblongus snail during anoxia exposure and post-anoxia recovery.
AB  - The effects of anoxic exposure and the post-anoxia aerobic recovery period on
      carbohydrate metabolism in the central nervous system (CNS) of the land snail
      Megalobulimus oblongus, an anoxia-tolerant land gastropod, were studied. The
      snails were exposed to anoxia for periods of 1.5, 3, 6, 12, 18, or 24 hr. In
      order to study the post-anoxia recovery phase, snails exposed to a 3-hr period of
      anoxia were returned to aerobic conditions for 1.5, 3, 6, or 15 hr. Glycogen and
      glucose concentrations in the CNS, hemolymph glucose concentration, and glycogen
      phosphorylase (active form, GPa) activity in the CNS were analyzed. Anoxia does
      not significantly affect the concentration of CNS glucose but induces
      hyperglycemia and a reduction of CNS GPa activity. The glycogen concentration was
      decreased at 12 hr of anoxia; however, by 18 and 24 hr in anoxia, the glycogen
      content was not significantly different from basal control values. During the
      post-anoxia period, the reduction in GPa activity and the increased hemolymph
      glucose concentration induced by anoxia returned to control values. These results
      suggest that the CNS of M. oblongus may use hemolymph glucose to fulfill the
      metabolic demands during anoxia. However, the hypothesis of tissue metabolic
      arrest cannot be excluded.

PMID- 15562447
TI  - Stomach remodeling-associated changes of H+/K+-ATPase beta subunit expression in
      Xenopus laevis and H+/K+-ATPase-dependent acid secretion in tadpole stomach.
AB  - Through subtractive hybridization, H+/K+-ATPase beta subunit mRNA, highly
      expressed in the larval stomach of Xenopus laevis, was isolated. In situ
      hybridization demonstrated that the H+/K+-ATPase beta subunit mRNA was
      exclusively expressed in manicotto gland cells of the larval stomach, not in any
      other cell. Northern blot analysis showed that metamorphosis-associated changes
      of the H+/K+-ATPase beta subunit mRNA expression in the stomach were
      characterized by high expression in tadpoles, a considerably lower expression in
      metamorphosing tadpoles, and a re-increase of expression in froglets. Further in
      situ hybridization showed that the decrease of expression correlated with the
      degeneration of larval type epithelium in the manicotto gland, while the re
      increase correlated with the differentiation of oxynticopeptic cells of the adult
      type stomach. Moreover, the H+/K+-ATPase beta subunit mRNA was expressed in adult
      epithelial primordia. Such changes were found in thyroid hormone-induced
      precocious metamorphosis. Based on studies using this ATPase as well as xP1 and
      PgC (pepsinogen C) as molecular markers, this study discusses a probable cell
      lineage involved in metamorphosis-associated stomach remodeling. The pH of
      luminal contents of the larval stomach was found to be lower than 2. In addition,
      the pH of an isolated stomach changed from 7.2 to lower than 4 after incubation
      in Ringer's solution, suggesting acid production from the larval stomach. This is
      the first demonstration of the H+/K+-ATPase-mediated acid production and
      secretion in the larval stomach of Xenopus laevis.

PMID- 15562448
TI  - Modulation of adenyl cyclase activity in the gills of Tapes philippinarum.
AB  - Adenyl cyclase (AC) plays a pivotal role in cell signaling. The AC system of
      bivalves has received little attention so far, and our study has been addressed
      to the characterization of AC properties in the gills of T. philippinarum. The
      enzyme showed a Km value of 0.77 mM for ATP in the presence of 5 mM Mg2+; in the
      absence of agonists, it was poorly affected by GTP, while it was stimulated by
      GTPgammaS and GppNHp up to 14-fold and 4-fold, respectively. Similarly to other
      invertebrates, the enzyme activity was scarcely stimulated by forskolin. The
      receptor agonist serotonin (5-HT) significantly stimulated the AC activity, and
      the pharmacological profile of the 5-HT receptor/s was as follows: (+)butaclamol
      > dihydroergocryptine > methysergide > prazosin > yohimbine. The AC activity was
      assessed in vitro in the presence of tributyltin chloride and HgCl2, which
      reduced the AC activity only at the highest dose tested (10-100 microM). Our data
      indicate the presence of a membrane-bound AC in gill membranes of T.
      philippinarum, coupled to Gs proteins and to a specific class of 5-HT receptors.
      Such receptors show a pharmacological profile slightly different from that
      reported for 5-HT invertebrate receptors cloned so far.

PMID- 15562449
TI  - Olfaction and the homing ability of pigeons raised in a tropical area in Brazil.
AB  - Several workers have investigated the effect of anosmia on pigeon navigation in
      different geographical locations because it has been suggested that homing
      behavior is based on different cues, such as olfactory cues, the Earth's magnetic
      field or infrasound, and that in the absence of one cue another would be used. In
      this situation, no cue is universally indispensable, including olfactory ones. In
      order to extend such observations to a novel biome, we observed the behaviour of
      192 young inexperienced birds raised in southeastern Brazil, a tropical area
      where olfactory tests had never been run before. The birds were released from
      eight symmetrically distributed sites 17 to 44 km from the loft. Half of these
      birds (experimentals) had been made temporarily anosmic by washing their
      olfactory mucosae with 4% solution of ZnSO4 the day before release, while
      controls were treated with Ringer solution. The results of release tests showed
      that anosmia totally impaired the navigational performance of experimental birds,
      which were unable to home from sites at relatively short distances from home (34
      44 km) and whose pooled initial bearings produced a (negative) homeward component
      not significantly different from 0. Homing performance of controls was
      significantly better, and their pooled vanishing bearings had a significant
      homeward component, in spite of much scatter in individual releases. We conclude
      that pigeon homing in the study area depends on olfactory information, even
      though local environmental conditions in the interior of the State of Sao Paulo,
      as in several other parts of the world, do not appear to be as favorable as Italy
      for the development of efficient olfactory navigation.

PMID- 15562450
TI  - Effect of salinity on expression of branchial ion transporters in striped bass
      (Morone saxatilis).
AB  - The time course of osmoregulatory adjustments and expressional changes of three
      key ion transporters in the gill were investigated in the striped bass during
      salinity acclimations. In three experiments, fish were transferred from fresh
      water (FW) to seawater (SW), from SW to FW, and from 15-ppt brackish water (BW)
      to either FW or SW, respectively. Each transfer induced minor deflections in
      serum [Na+] and muscle water content, both being corrected rapidly (24 hr).
      Transfer from FW to SW increased gill Na+,K+-ATPase activity and Na+,K+,2Cl- co
      transporter expression after 3 days. Abundance of Na+,K+-ATPase alpha-subunit
      mRNA and protein was unchanged. Changes in Na+,K+,2Cl- co-transporter protein
      were preceded by increased mRNA expression after 24 hr. Expression of V-type H+
      ATPase mRNA decreased after 3 days. Transfer from SW to FW induced no change in
      expression of gill Na+,K+-ATPase. However, Na+,K+,2Cl- co-transporter mRNA and
      protein levels decreased after 24 hr and 7 days, respectively. Expression of H+
      ATPase mRNA increased in response to FW after 7 days. In BW fish transferred to
      FW and SW, gill Na+,K+-ATPase activity was stimulated by both challenges,
      suggesting both a hyper- and a hypo-osmoregulatory response of the enzyme.
      Acclimation of striped bass to SW occurs on a rapid time scale. This seems partly
      to rely on the relative high abundance of gill Na+,K+-ATPase and Na+,K+,2Cl- co
      transporter in FW fish. In a separate study, we found a smaller response to SW in
      expression of these ion transport proteins in striped bass when compared with the
      less euryhaline brown trout. In both FW and SW, NEM-sensitive gill H+-ATPase
      activity was negligible in striped bass and approximately 10-fold higher in brown
      trout. This suggests that in striped bass Na+-uptake in FW may rely more on a
      relatively high abundance/activity of Na+,K+-ATPase compared to trout, where H+
      ATPase is critical for establishing a thermodynamically favorable gradient for
      Na+-uptake.

PMID- 15562451
TI  - Effects of exercise on plasma catecholamine levels in the toad, Bufo paracnemis:
      role of the adrenals and neural control.
AB  - Resting plasma epinephrine (E) and norepinephrine (N) concentrations for intact
      toads (Bufo paracnemis) were 5.57+/-1.0 and 0.88+/-0.38 ng/ml, respectively.
      Exercise induced a significant increase in heart rate, blood pressure and plasma
      epinephrine (about 4.3 times), whereas norepinephrine remained unchanged. The
      resting [E]/[N] ratio was 6.3 and increased to 32.9 during exercise. Adrenal
      denervation did not alter the basal plasma catecholamine or norepinephrine levels
      after exercise, but prevented the increase in epinephrine during exercise,
      suggesting that in the intact toad this increase is due to adrenal secretion
      whereas resting norepinephrine may be liberated by extra-adrenal chromaffin
      tissues. This also suggests that the adrenal glands can release selectively the
      two catecholamines. The increases in heart rate and blood pressure in denervated
      toads were not significantly different from those of intact animals, suggesting
      that during exercise the sympathetic nerves play the main role in inducing
      cardiovascular responses. Spinal transection induced a significant increase in
      basal norepinephrine levels, which remained elevated after exercise. Since spinal
      toads are unable to perform spontaneous movements it is possible that this
      increase may be caused by this stressful condition. The increases in heart rate
      and blood pressure observed in spinal toads during exercise may be due to direct
      mechanical effects of venous return on the heart.

PMID- 15562452
TI  - Endocrine response to fasting in the overwintering captive raccoon dog
      (Nyctereutes procyonoides).
AB  - The raccoon dog (Nyctereutes procyonoides) is an omnivorous canid utilizing the
      passive wintering strategy in the boreal climate. Farmed raccoon dogs (n=12) were
      randomly assigned into two study groups on 26 November 2003. Between 3 December
      2003 and 27 January 2004, half of the animals were fasted for 8 weeks and plasma
      weight-regulatory hormone concentrations determined on 26 November and 30
      December 2003 and on 27 January 2004. The plasma peptide YY, ghrelin, and growth
      hormone (GH) concentrations increased due to food deprivation, while the T4 and
      Acrp30 concentrations decreased. Furthermore, the plasma GH concentrations were
      higher in the fasted raccoon dogs than in the fed animals, which had higher
      plasma insulin, glucagon, and T4 concentrations. However, fasting had no effect
      on the plasma leptin concentrations. The results confirm previous findings with
      unchanged leptin levels in fasting carnivores. Increased GH levels probably
      contribute to increased lipolysis and mobilization of fat stores. Ghrelin can
      also enhance lipolysis by increasing the GH levels. The decreased levels of T4
      may reduce the metabolic rate. The plasma dopamine concentrations decreased due
      to fasting unlike observed previously in rats. Together with the unaffected
      adrenaline, noradrenaline, and cortisol concentrations, this suggests that food
      deprivation in winter does not cause stress to the raccoon dog but is an integral
      part of its natural life history.

PMID- 15562453
TI  - Production and progeny testing of androgenetic rosy barb Puntius conchonius.
AB  - Protocol for androgenetic cloning of the rosy barb, Puntius conchonius, with
      contrasting gray and golden strains is described. At the intensity of 4.2 W/m2,
      UV irradiation for 3.0 min inactivates the maternal genome in eggs of the gray
      barb. Following activation by the golden barb sperm, 24-min old eggs are shocked
      at 41 degrees C for 2 min to restore diploidy. Maternal genomic inactivation is
      confirmed by the (i) golden body color, (ii) karyotyping, and (iii) progeny
      testing of F1-F3 progenies. Estimates of stage-specific mortality of haploid and
      diploid androgenotes indicate no change in the time scale or developmental
      sequence, when sperm of related strain is used for activation, and when haploid
      genome regulates the development. Survival of androgenetic clones remains
      constant for the F1, F2, and F3 progenies and is about 15% and 7% at hatching and
      sexual maturity, respectively. Homozygosity of the androgenotes is shown to
      inflict greater mortality. Between F1 and F3 generations, the heterozygosity of
      the androgenetic clone is decreased, as evidenced by reduction in size hierarchy.
      Though the reproductive performance of the F1, F2, and F3 supermales is superior
      to the normal ones, the realized fecundity remains equal around 80 progenies per
      brood. The 92 crosses involving 16 supermales and 10 normal dams yield 75-100%
      male progenies, confirming the possible operation of XXfemale symbol:XYmale
      symbol sex determination system. The frequency of unexpected occurrence of female
      progenies is about 8%, the causes for which are discussed.

PMID- 15562454
TI  - Medication errors in pediatrics--the octopus evading defeat.
AB  - Medication errors have come to the forefront in healthcare and oversight
      organizations as well as to the public over the past several years. There has
      been an increasing focus on this area of patient care requiring more intensive
      evaluation and intervention to prevent these errors. Although it is difficult to
      ascertain the true occurrence of medication errors, they may occur as frequently
      as once in every 20 orders. Children are at higher risk for medication errors and
      adverse drug events for numerous reasons. Not only is there great variability in
      weight and body surface area in this population, there is also significant
      differences in the pharmacokinetics and pharmacodynamics of many medications when
      compared to adults. In addition, our knowledge of pharmacogenetics and phenotypic
      ontogeny must be applied. Sources of medication errors are identified, and
      specific examples and solutions to improve medication use in children are
      provided. It is critical to have 1) personnel trained in pediatrics to prescribe,
      prepare, dispense and administer medications, 2) a quality review system in place
      to review drug use and medication errors, and 3) to implement computerized
      physician order entry with decision support and other tools in the next decade to
      improve pharmacologic therapy for pediatric patients.

PMID- 15562455
TI  - Balloon crush: new tool in bifurcation treatment armamentarium.

PMID- 15562456
TI  - Nature and prevention of errors in anesthesiology.

PMID- 15562457
TI  - Errors in laparoscopic surgery.
AB  - Laparoscopic surgery is the most significant advancement in the field of surgery
      over the past 15 years. This minimal access approach has been widely embraced and
      adopted to many common operations. Demonstrated benefits include decreased post
      operative pain, shorter lengths of in-patient hospitalization, increased patient
      acceptance, and a more rapid return to gainful employment. With its ever-growing
      popularity, it has become fertile ground for civil litigation, ranking along with
      birth injuries and failure to diagnose cancer. A brief synopsis of the history of
      its evolution is presented along with general and specific comments concerning
      potential errors as they relate to specific common operations which are commonly
      done utilizing this technique.

PMID- 15562458
TI  - AD lesions and infarcts in demented and non-demented Japanese-American men.
AB  - Neocortical neuritic plaques and neurofibrillary tangles are hallmark
      neuropathological lesions of dementia. Concomitant cerebrovascular lesions
      increase dementia severity in patients meeting neuropathological criteria for
      Alzheimer's disease and contribute to cognitive impairment in persons with mild
      entorhinal Alzheimer lesions. This study investigates whether individuals with
      sparse neocortical neuritic plaques experience increased odds of crossing the
      threshold to clinical dementia when they have coexistent cerebrovascular lesions.
      Dementia examinations were given to 3,734 men during the 1991-1993 Honolulu-Asia
      Aging Study examination and to 2,603 men during the 1994-1996 examination. Lesion
      quantification was done without clinical data. Among 333 autopsied men, 120 had
      dementia, 115 had marginal results, and 98 had normal cognition. In men with
      neurofibrillary tangles, dementia frequency increased with increasing neuritic
      plaque density, and increased further in the presence of cerebrovascular lesions.
      The association was strongest in men with sparse neuritic plaques (1-3/mm(2))
      where dementia frequency more than doubled with coexistent cerebrovascular
      lesions (45 vs 20%). Among all dementia cases, 24% were linked to cerebrovascular
      lesions. Findings suggest cerebrovascular lesions are associated with a marked
      excess of dementia in cases with low neuritic plaque frequency. Prevention of
      cerebrovascular lesions may be critically important in preserving late-life
      cognitive function.

PMID- 15562459
TI  - Another look at medical error.
AB  - Medical error continues to be a topic of discussion. Blaming the physician or
      nurse for error is too simplistic and may serve to blur larger system problems
      from being identified and addressed. This article considers recent history of
      assignment of errors from a quality assurance perspective, multiple paths which
      result in error, reviewing the 1999 Institute of Medicine report and looking
      beyond the numbers to issues that can only be assigned to systems.

PMID- 15562460
TI  - Medical errors: a challenge to all physicians.

PMID- 15562461
TI  - Commentary on the professional career of John S. Spratt, Jr., MD, MPH.

PMID- 15562462
TI  - Errors in pathology and laboratory medicine: consequences and prevention.
AB  - Reducing errors and improving quality are an integral part of Pathology and
      Laboratory Medicine. The rate of errors is reviewed for the pre-analytical,
      analytical, and post-analytical phases for a specimen. The quality systems in
      place in pathology today are identified and compared with benchmarks for quality.
      The types and frequency of errors and quality systems are reviewed for surgical
      pathology, cytopathology, clinical chemistry, hematology, microbiology, molecular
      biology, and transfusion medicine. Seven recommendations are made to reduce
      errors in future for Pathology and Laboratory Medicine.

PMID- 15562463
TI  - Role of the pharmacist in reducing medication errors.

PMID- 15562464
TI  - A systems approach to error prevention in medicine.
AB  - Minimization of medical errors is at the core of all clinical medical practices.
      The first tenet of care is to do no harm. The enormous complexity of modern
      medical care has made error detection and management extremely difficult.
      Traditional deterministic methods of solving the "error issue" cannot cope with
      the huge number of potential errors that are possible. Systems thinking and
      approach to error reduction provides a different avenue for tackling this
      challenging dilemma. The intent of this article is to introduce a systems view of
      medical errors and to explain how it can provide new insights about dealing with
      massively complex organizations such as the healthcare system. Important features
      include an understanding of system relationships, sources of error, human
      components, optimization versus perfection in systems and the interrelationships
      between human and system processes.

PMID- 15562465
TI  - The psychology of error in relation to medical practice.
AB  - There is a broad effort underway to reduce the frequency of medical error. This
      effort will be facilitated by understanding the causes of human error and the
      methods that serve to reduce it in settings comparable to medical practice. To
      serve this end, this article is a review of cognitive psychology as it relates to
      the origins of human error and an application of that material to issues that
      arise in medical practice.

PMID- 15562466
TI  - 4 T actively detunable transmit/receive transverse electromagnetic coil and 4
      channel receive-only phased array for (1)H human brain studies.
AB  - The design and construction of a 4 T transverse electromagnetic (TEM)
      transmit/receive head coil and a four-channel phased array receive-only RF system
      are described. To enable both high-resolution imaging of the entire brain and
      high-resolution spectroscopic imaging, active PIN diode decoupling was used in
      both the TEM resonator and each surface coil in the array. This configuration
      allows for both transmission and reception from the volume coil as well as
      reception from the phased array. The surface coils were decoupled by overlapping
      the coils and using preamplifier decoupling. Since at high frequencies
      construction of a lumped element matching quarter wavelength transformer, an
      important component of the preamplifier decoupling, becomes difficult, a
      transmission line approach was used. The system was tested and compared to a TEM
      volume transmit/receive head coil. A four- to sixfold improvement in signal-to
      noise ratio from the sensitive volume of the array was achieved.

PMID- 15562468
TI  - Reduction of magnetic field inhomogeneity artifacts in echo planar imaging with
      SENSE and GESEPI at high field.
AB  - Geometric distortion, signal-loss, and image-blurring artifacts in echo planar
      imaging (EPI) are caused by frequency shifts and T(2)(*) relaxation distortion of
      the MR signal along the k-space trajectory due to magnetic field inhomogeneities.
      The EPI geometric-distortion artifact associated with frequency shift can be
      reduced with parallel imaging techniques such as SENSE, while the signal-loss and
      blurring artifacts remain. The gradient-echo slice excitation profile imaging
      (GESEPI) method has been shown to be successful in restoring tissue T(2)(*)
      relaxation characteristics and is therefore effective in reducing signal-loss and
      image-blurring artifacts at a cost of increased acquisition time. The SENSE and
      GESEPI methods are complementary in artifact reduction. Combining these two
      techniques produces a method capable of reducing all three types of EPI artifacts
      while maintaining rapid acquisition time.

PMID- 15562469
TI  - In vivo quantification of T1rho using a multislice spin-lock pulse sequence.
AB  - A multislice spin-lock (MS-SL) pulse sequence is implemented on a clinical
      scanner to acquire multiple images with spin-lock-generated contrast of the knee
      joints of six healthy human subjects. The MS-SL sequence produces images with
      T1rho contrast with an additional factor of intrinsic T2rho weighting, which
      hinders direct measurement of T1rho. A method is presented to compensate the MS
      SL-generated data with regard to T2rho in an effort to accurately calculate
      multislice T1rho maps in a feasible experimental time. The T2rho-compensated
      multislice T1rho maps produced errors in the measurement of T1rho in healthy
      patellar cartilage of approximately 5% compared to the gold standard measurement
      of T1rho acquired with single-slice spin-lock pulse sequence. The MS-SL sequence
      has potential as an important clinical tool for the acquisition of multislice
      T1rho-weighted images and/or quantitative multislice T1rho maps.

PMID- 15562470
TI  - Partial-volume effect on ischemic tissue-fate delineation using quantitative
      perfusion and diffusion imaging on a rat stroke model.
AB  - Partial-volume effects (PVE) in stroke imaging could hinder proper delineation of
      normal, ischemic, and at-risk tissues. Cerebral-blood-flow (CBF) and apparent
      diffusion coefficient (ADC) were measured at high and low resolution (HR = 128 x
      128, LR = 64 x 64) in focal ischemia in rats during the acute phase. The data
      were evaluated for PVE on ischemic tissue classification on a pixel-by-pixel
      basis and the misclassified pixels were quantified as ischemia progressed. The
      main drawbacks of high-resolution imaging are reduced temporal resolution and/or
      signal-to-noise ratio. The high- versus low-resolution scatterplots and
      histograms of pixels along the normal-abnormal boundaries in the ADC and CBF maps
      showed marked ischemia-related PVE. By comparison with the homologous regions in
      the contralateral normal hemisphere, the effect of increased noise and intrinsic
      tissue heterogeneity due to high resolution could be distinguished from ischemia
      related PVE. Degrading the high-resolution (128 x 128) data to a 64 x 64 or 32 x
      32 matrix increased the severity of PVE. Zero-filling of low-resolution (64 x 64)
      data to 128 x 128 also increased PVE. It was concluded that PVE: (1)
      misclassified substantial pixels along the normal-abnormal boundaries, (2)
      overestimated abnormal volumes at the expense of mostly "at-risk" and some
      "normal" tissues, (3) were more severe at the early time points postischemia, and
      (4) confounded the interpretation of the operationally defined ischemic penumbra.

PMID- 15562471
TI  - Improving the segmentation of therapy-induced leukoencephalopathy in children
      with acute lymphoblastic leukemia using a priori information and a gradient
      magnitude threshold.
AB  - Reliably quantifying therapy-induced leukoencephalopathy is a challenging task
      due to the similarity between its MR properties and those of normal tissues.
      Multispectral MR images were analyzed for 15 children treated for acute
      lymphoblastic leukemia. Three different analysis techniques were compared to
      examine improvements in the segmentation accuracy of leukoencephalopathy versus
      manual tracings by two experienced observers. The original technique used a white
      matter mask based on the segmentation of the first serial examination of each
      patient and no a priori information. The modified techniques combine spatially
      normalized a priori maps as input and a gradient magnitude threshold. The second
      technique used a 2D threshold, while the third algorithm utilized a 3D threshold.
      MR images were segmented with a Kohonen self-organizing map for all three
      algorithms. Kappa values were compared for the three techniques to each observer
      and statistically significant improvements were seen between the original and
      third algorithms (Observer 1: 0.651, 0.744, P = 0.015; Observer 2: 0.603, 0.699,
      P = 0.024). More accurate and reliable quantification reduces the amount of
      variance in MR measures and facilitates clinical trials to determine the clinical
      significance of leukoencephalopathy in this vulnerable population.

PMID- 15562472
TI  - Measurement and correction of respiration-induced B0 variations in breast 1H MRS
      at 4 Tesla.
AB  - Respiratory motion is well known to cause artifacts in magnetic resonance
      spectroscopy (MRS). In MRS of the breast, the dominant artifact is not due to
      motion of the breast itself, but rather it is produced by B0 field distortions
      associated with respiratory motion of tissues in the chest and abdomen. This
      susceptibility artifact has been reported to occur in the brain, but it is more
      apparent in the breast due to the anatomic proximity of the lungs. In the breast,
      these B0 distortions cause shot-to-shot frequency shifts, which vary an average
      of 24 Hz during a typical 1H MRS scan at 4 T. This variation can be corrected
      retrospectively by frequency shifting individual spectra prior to averaging. If
      not corrected, these shifts reduce spectral resolution and increase peak fitting
      errors. This work demonstrates the artifact, describes a method for correcting
      it, and evaluates its impact on quantitative spectroscopy. When the artifact is
      not corrected, quantification errors increase by an average of 28%, which
      dramatically impacts the ability to measure metabolite resonances at low signal
      to-noise ratios.

PMID- 15562473
TI  - Evaluation of variable line-shape models and prior information in automated 1H
      spectroscopic imaging analysis.
AB  - Analysis of in vivo short TE 1H spectra is complicated by broad baseline signal
      contributions and resonance line-shape distortions. Although the assumptions of
      ideal metabolite resonance line-shapes and slowly varying baseline signals can be
      used to separate these signals, the presence of broad or asymmetric line-shapes
      can invalidate this model. More complex line-shape models are computationally
      expensive or difficult to constrain, particularly for the low signal-to-noise
      commonly found for in vivo MR spectroscopic imaging applications. In this study,
      two time-domain models for fitting variable spectral line-shapes are examined,
      one using B-splines and another using summed sinusoids. The methods were verified
      using both phantom and human data, and Monte Carlo simulations were used to
      evaluate variations in calculated metabolite amplitudes due to interactions
      between the baseline and line-shape estimations. Additional studies investigated
      the use of prior line-shape information, obtained from either a water MRSI
      measurement or calculations from B(0) maps, to determine parameter starting
      values or optimization constraints. Both line-shape models showed the ability to
      fit the variety of line-shapes present in both the phantom and human MRSI data,
      with similar or improved accuracy over a Gaussian line-shape model; however, this
      improvement resulted in only minor improvement for the high-SNR phantom data and
      moderate improvements in regions with asymmetry for the fitted in vivo metabolite
      images. The use of prior line-shape information was of most benefit when applied
      toward setting optimization constraints but was of limited benefit when used to
      define initial starting values.

PMID- 15562474
TI  - MRI of transplanted pancreatic islets.
AB  - A promising treatment method for type 1 diabetes mellitus is transplantation of
      pancreatic islets containing beta-cells. The aim of this study was to develop an
      MR technique to monitor the distribution and fate of transplanted pancreatic
      islets in an animal model. Twenty-five hundred purified and magnetically labeled
      islets were transplanted through the portal vein into the liver of experimental
      rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic
      islets were clearly visualized in the liver in both diabetic and healthy rats as
      hypointense areas on T2*-weighted MR images during the entire measurement period.
      Transmission electron microscopy confirmed the presence of iron-oxide
      nanoparticles inside the cells of the pancreatic islets. A significant decrease
      in blood glucose levels in diabetic rats was observed; normal glycemia was
      reached 1 week after transplantation. This study, therefore, represents a
      promising step toward possible clinical application in human medicine.

PMID- 15562475
TI  - Imaging therapeutic response in human bone marrow using rapid whole-body MRI.
AB  - Whole-body imaging of therapeutic response in human bone marrow was achieved
      without introduced contrast agents using diffusion-weighted echo-planar magnetic
      resonance imaging of physiologic water. Bone marrow disease was identified
      relative to the strong overlying signals from water and lipids in other anatomy
      through selective excitation of the water resonance and generation of image
      contrast that was dependent upon differential nuclear relaxation times and self
      diffusion coefficients. Three-dimensional displays were generated to aid image
      interpretation. The geometric distortion inherent in echo-planar imaging
      techniques was minimized through the acquisition of multiple axial slices at up
      to 12 anatomic stations over the entire body. Examples presented include the
      evaluation of therapeutic response in bone marrow during cytotoxic therapy for
      leukemia and metastatic prostate cancer and during cytokine administration for
      marrow mobilization prior to stem cell harvest.

PMID- 15562476
TI  - Triple contrast technique for black blood imaging with double inversion
      preparation.
AB  - This work reports on the development of a pulse sequence to simultaneously
      acquire proton density, T(1), and T(2) weighted images in a single magnetization
      prepared fast spin echo acquisition. The technique is based upon the application
      of a magnetization preparation consisting of a global inversion followed by slice
      selective 180 degrees and 90 degrees pulses to prepare the signal of specific
      slices. Slices are acquired in an interleaved manner with time delays appropriate
      for the desired image contrasts. Data acquisition is repeated for all
      combinations of slice interleaving covering the region of interest until images
      from all slice locations have been acquired with all desired image contrasts. The
      multiple image contrasts obtained with this technique should be useful in
      applications where discrimination between different types of tissue components is
      desired, such as in the analysis of plaque in cervical carotid artery disease.

PMID- 15562477
TI  - Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation
      information during brain activation.
AB  - Simultaneous acquisition of complementary functional hemodynamic indices
      reflecting different aspects of brain activity would be a valuable tool for
      functional brain-imaging studies offering enhanced detection power and improved
      data interpretation. As such, a new MRI technique is presented that is able to
      achieve concurrent acquisition of three hemodynamic images based primarily on the
      changes of cerebral blood volume, blood flow, and blood oxygenation,
      respectively, associated with brain activation. Specifically, an inversion
      recovery pulse sequence has been designed to measure VASO (vascular space
      occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation
      level-dependent) signals in a single scan. The MR signal characteristics in this
      sequence were analyzed, and image parameters were optimized for the simultaneous
      acquisition of these functional images. The feasibility and efficacy of the new
      technique were assessed by brain activation experiments with visual stimulation
      paradigms. Experiments on healthy volunteers showed that this technique provided
      efficient image acquisition, and thus higher contrast-to-noise ratio per unit
      time, compared with conventional techniques collecting these functional images
      separately. In addition, it was demonstrated that the proposed technique was able
      to be utilized in event-related functional MRI experiments, with potential
      advantages of obtaining accurate transient information of the activation-induced
      hemodynamic responses.

PMID- 15562478
TI  - Hyperpolarized (3)He MRI of mouse lung.
AB  - Hyperpolarized (3)He images of mouse lung are presented. Ventilation images and
      measurements of (3)He apparent diffusion coefficient (ADC) are reported in
      healthy mice, and preliminary studies of emphysema and lung cancer in mice are
      described using these techniques. The design and operation of an electronically
      controlled small-animal ventilator to deliver the hyperpolarized gas and control
      animal respiration are described. Images are acquired using an asymmetric
      gradient echo imaging method to enhance the signal-to-noise ratio of the rapidly
      diffusing (3)He. In mice with elastase-induced emphysema, the whole-lung average
      ADC is greater by approximately 25%, a statistically significant difference,
      compared to healthy animals. By contrast, mice exposed to cigarette smoke for up
      to 12 months reveal no statistically relevant increases in ADC, although
      emphysema was not confirmed in these mice. A study of lung cancer (melanoma) in
      mice is also presented. While tumors are shown to cause substantial ventilation
      defects in the lung, these defects appear confined to the cancerous regions and
      do not extend to large-scale regions of the lung distal to the tumors.

PMID- 15562479
TI  - Rapid measurement of pulse wave velocity via multisite flow displacement.
AB  - A MR method is presented for measuring pulse wave velocity (PWV) and its
      application to assessing stiffness in the human thoracic aorta. This one
      dimensional (1D) flow displacement method applies a single RF comb excitation to
      the vessel, followed by an oscillating frequency encoding gradient, each
      oscillation providing a 1D projection of the vessel, enabling one to track fluid
      motion. The currently implemented sequence excites nine slices within a 20-cm
      length of vessel and has a temporal resolution of 2.03 msec and a total
      acquisition time of 140 msec. Offline-reconstructed position-versus-time plots
      show curvilinear flow displacement trajectories corresponding to fluid motion at
      each of the excitation positions. The PWV can be reliably calculated by curve
      fitting these trajectories to a model. In vitro studies using compliant tubes
      demonstrate no significant difference between results obtained using this method
      and those directly obtained using pressure transducers. Compared to another MR
      method previously developed in our laboratory, the proposed method displays
      improved temporal resolution and enhanced ability to extract PWV from vessels
      exhibiting low peak flow velocity. Preliminary data suggest that this method is
      feasible for in vivo application and may provide a more accurate estimation of
      aortic wave velocity among subjects exhibiting low peak flow velocity, such as
      the elderly or those with impaired cardiac function.

PMID- 15562480
TI  - Gradient field switching as a source for artifacts in MR imaging of metallic
      stents.
AB  - Metallic implants, such as stents, have long been a concern in magnetic resonance
      imaging (MRI). In addition to safety issues, they are commonly associated with
      image artifacts. The mechanisms of radiofrequency- (RF) and susceptibility
      induced artifacts have been thoroughly investigated. However, gradient-switching
      induced artifacts have not been analyzed. In this study it was demonstrated that
      gradient switching may be a source of artifacts in metallic stent MR imaging.
      These artifacts differ from those caused by the RF pulse. A theoretical
      explanation is provided as well.

PMID- 15562481
TI  - Quantitative "magnetic resonance immunohistochemistry" with ligand-targeted (19)F
      nanoparticles.
AB  - Unstable atherosclerotic plaques exhibit microdeposits of fibrin that may
      indicate the potential for a future rupture. However, current methods for
      evaluating the stage of an atherosclerotic lesion only involve characterizing the
      level of vessel stenosis, without delineating which lesions are beginning to
      rupture. Previous work has shown that fibrin-targeted, liquid perfluorocarbon
      nanoparticles, which carry a high payload of gadolinium, have a high sensitivity
      and specificity for detecting fibrin with clinical (1)H MRI. In this work, the
      perfluorocarbon content of the targeted nanoparticles is exploited for the
      purposes of (19)F imaging and spectroscopy to demonstrate a method for
      quantifiable molecular imaging of fibrin in vitro at 4.7 T. Additionally, the
      quantity of bound nanoparticles formulated with different perfluorocarbon species
      was calculated using spectroscopy. Results indicate that the high degree of
      nanoparticle binding to fibrin clots and the lack of background (19)F signal
      allow accurate quantification using spectroscopy at 4.7 T, as corroborated with
      proton relaxation rate measurements at 1.5 T and trace element (gadolinium)
      analysis. Finally, the extension of these techniques to a clinically relevant
      application, the evaluation of the fibrin burden within an ex vivo human carotid
      endarterectomy sample, demonstrates the potential use of these particles for
      uniquely identifying unstable atherosclerotic lesions in vivo.

PMID- 15562482
TI  - New approaches to receiver operating characteristic methods in functional
      magnetic resonance imaging with real data using repeated trials.
AB  - Receiver operating characteristic (ROC) methods are useful tools for evaluating
      the sensitivity and specificity of various postprocessing algorithms used in fMRI
      data analysis. New ROC methods using real fMRI data are proposed that improve a
      previously introduced method by Le and Hu (Le and Hu, NMR Biomed 1997;10:160
      164). The proposed methods provide more accurate means of estimating the true ROC
      curve from real data and thereby aid in the comparative evaluation of a wide
      range of postprocessing tools in fMRI. The mathematical relationships between
      different ROC curves are explored for a comparison of different ROC methods.
      Examples using real and simulated data are provided to illustrate the ideas
      involved.

PMID- 15562483
TI  - Novel double contrast MRI technique for intramyocardial detection of
      percutaneously transplanted autologous cells.
AB  - Bone marrow cells (BMC) labeled with iron particles can be injected into the
      heart and detected with MRI. Improvement in conspicuity of labelled cells would
      be advantageous. This study examined if double contrast with iron oxide and Gd
      DTPA enhances cell MRI after transvascular transplantation in myocardial
      infarction. Ten pigs with week-old myocardial infarction had transvascular peri
      infarct delivery of microspheres alone (Group I, n = 3) or mixed with iron
      labeled BMCs (Group II, n = 7). Gradient-echo MRI before and 1 min after systemic
      Gd-DTPA administration produced regions of interest with hypoenhancement that
      were compared to contralateral regions for contrast-to-noise (CNR) and signal-to
      noise (SNR) ratios. All hearts were harvested for gross and microscopic analysis.
      Areas of focal hypoenhancement corresponding to the BMCs were detected in the
      myocardium in Group II. Early after administration of Gd-DTPA CNR increased from
      17.58 +/- 8.5 to 27.25 +/- 15.8 (P < 0.05) and SNR from 24.87 +/- 9.6 to 35.08 +/
      15.5 (P < 0.05). There was no hypoenhancement in Group I. Tissue examination
      confirmed presence of iron-containing cells and microspheres in corresponding
      segments of the heart. The distribution of microspheres was similar between the
      groups. Double contrast with cellular iron and Gd-DTPA in surrounding myocardium
      resulted in improved cell localization by MRI.

PMID- 15562484
TI  - Fast Spiral two-point Dixon technique using block regional off-resonance
      correction.
AB  - The Spiral two-point Dixon (Spiral 2PD) technique has recently been proposed as a
      method for unambiguous water-fat decomposition in spiral imaging. It also
      corrects for off-resonance blurring artifacts using only two data sets. In the
      Spiral 2PD technique, several predetermined off-resonance frequencies are tested
      to both separate water and fat signals and deblur the decomposed images.
      Unfortunately, the algorithm is computationally quite intensive since the range
      of tested frequencies must be set sufficiently large to span the full range of
      anticipated B(0) variation over the scanned objects. The block regional off
      resonance correction (BRORC) algorithm corrects for off-resonance blurring
      artifacts block by block through the reconstructed image and usually provides
      several times higher computational efficiency than the conventional frequency
      segmented off-resonance correction algorithm. This work shows that both water-fat
      decomposition and blurring artifact correction can be performed block by block
      using two spiral images with different TEs and that this new technique (BRORC
      Spiral2PD technique) significantly improves the computational efficiency of other
      Spiral 2PD algorithms, opening new opportunities for spiral imaging.

PMID- 15562485
TI  - POCSENSE: POCS-based reconstruction for sensitivity encoded magnetic resonance
      imaging.
AB  - A novel method for iterative reconstruction of images from undersampled MRI data
      acquired by multiple receiver coil systems is presented. Based on Projection onto
      Convex Sets (POCS) formalism, the method for SENSitivity Encoded data
      reconstruction (POCSENSE) can be readily modified to include various linear and
      nonlinear reconstruction constraints. Such constraints may be beneficial for
      reconstructing highly and overcritically undersampled data sets to improve image
      quality. POCSENSE is conceptually simple and numerically efficient and can
      reconstruct images from data sampled on arbitrary k-space trajectories. The
      applicability of POCSENSE for image reconstruction with nonlinear constraining
      was demonstrated using a wide range of simulated and real MRI data.

PMID- 15562486
TI  - Harmonic phase MR tagging for direct quantification of Lagrangian strain in rat
      hearts after myocardial infarction.
AB  - The utility of harmonic phase (HARP) analysis was recently demonstrated in humans
      and large animals as a technique for rapid and automatic analysis of tagged
      magnetic resonance images. In the current study, the applicability and accuracy
      of HARP analysis for automatic strain quantification in small animals were
      investigated. A validation study was performed on seven postinfarct rats and
      seven age-matched controls. A method for direct computation of 2D Lagrangian
      strain fields from spatial derivatives of HARP images was also developed in this
      paper. The results of HARP analysis were evaluated by comparison with those of
      homogeneous strain analysis employing finite element method and manual tag
      tracking. Both methods were validated with simulated digital images. Compared to
      conventional homogeneous strain analysis, HARP analysis yielded similar results
      in the assessment of regional strain patterns in both control and infarct rats.
      Both methods detected a reduction in maximal stretch and shortening in infarct
      rats. Our results suggest that HARP analysis can also be applied to quantify
      alterations in regional myocardial wall motion in small animals.

PMID- 15562487
TI  - Experimental application of thermosensitive paramagnetic liposomes for monitoring
      magnetic resonance imaging guided thermal ablation.
AB  - The use of a liposomal paramagnetic agent with a T(1)-relaxivity that increases
      markedly at temperatures above the phase transition temperature (T(m)) of the
      liposomal membrane was evaluated during magnetic resonance imaging (MRI) guided
      hyperthermia ablation. A neodymium-yttrium aluminum garnet (Nd-YAG) laser unit
      and a radiofrequency ablation system were used for tissue ablation in eight
      rabbit livers in vivo. One ablation was made in each animal prior to
      administration of the liposomal agent. Liposomes with a T(m) of 57 degrees C
      containing gadodiamide (GdDTPA-BMA) were injected iv, and two additional
      ablations were performed. T(1)-weighted scans were performed in heated tissue,
      after tissue temperature had normalized, and 15-20 min after normalization of
      tissue temperature. Increase in signal intensity (DeltaSI) for ablations prior to
      injection of the agent was 13.0% (SD = 5.7) for the laser group and 9.1% (SD =
      7.9) for the radiofrequency group. Signal intensity after administration of the
      agent unrelated to heating was not statistically significant (DeltaSI = 1.4%, P =
      0.35). For ablations made after injection of the agent, a significant increase
      was found in the laser (DeltaSI = 34.5%, SD = 11.9) and radiofrequency group
      (DeltaSI = 21.6%, SD = 22.7). The persistent signal enhancement found in areas
      exposed to a temperature above the threshold temperature above T(m) allows
      thermal monitoring of MRI guided thermal ablation.

PMID- 15562488
TI  - Interscan registration using navigator echoes.
AB  - A common problem in clinical MRI is anatomic misalignment of imaging slices
      across successive examinations. This unnecessarily complicates the radiologic
      assessment of anatomic change over time on serial MRI studies. To address this
      problem, spherical navigator echoes, which can detect rigid body motion in all
      six degrees of freedom, were used to guide spatial location and orientation
      adjustments to an exam prescription to match the reference frame of images
      acquired in an earlier exam. An initial linear navigator echo is also necessary
      to effect coarse Z translation adjustments prior to fine six degrees of freedom
      adjustment with a spherical navigator echo. Results of this technique are
      presented for head image volumes of five volunteers. Each volunteer was imaged on
      two scanners. In all cases, the reference frame adjustments provided by the
      navigator echoes substantially improved the alignment of the latter exam and
      performed well compared to retrospective image-based registration.

PMID- 15562489
TI  - Exogenous contrast agent improves sensitivity of gradient-echo functional
      magnetic resonance imaging at 9.4 T.
AB  - Relative to common clinical magnetic field strengths, higher fields benefit
      functional brain imaging both by providing additional signal for high-resolution
      applications and by improving the sensitivity of endogenous contrast due to the
      blood oxygen level dependent (BOLD) mechanism, which has limited detection power
      at low magnetic fields relative to the use of exogenous contrast agent. This
      study evaluates the utility of iron oxide contrast agent for gradient echo
      functional MRI at 9.4 T in rodents using cocaine and methylphenidate as stimuli.
      Relative to the BOLD method, the use of high iron doses and short echo times
      provided a roughly twofold global increase in functional sensitivity, while also
      suppressing large vessel signal and reducing susceptibility artifacts.
      Furthermore, MRI measurements of the functional percentage change in cerebral
      blood volume (CBV) showed excellent agreement with results obtained at much lower
      magnetic field strengths, demonstrating that MRI estimates of this quantity are
      roughly independent of magnetic field when appropriate techniques are employed.
      The derived field dependencies for relative sensitivity and MRI estimates of the
      percentage change in CBV suggest that the benefits provided by exogenous agents
      will persist even at much higher magnetic fields than 9.4 T.

PMID- 15562490
TI  - B factor dependence of the temporal characteristics of brain activation using
      dynamic apparent diffusion coefficient contrast.
AB  - Functional MRI studies to date have been generally performed using the blood
      oxygenation level dependent (BOLD) contrast mechanism. Recently, it has been
      proposed that dynamic change in the apparent diffusion coefficient (ADC),
      measured using intravoxel incoherent motion (IVIM) weighting, can be used as a
      robust functional contrast mechanism. Based on the differences in the timing
      characteristics compared to the BOLD activation, the ADC contrast can be
      selectively sensitized to upstream vascular pools (e.g., arterial networks). In
      this study we further investigated the timing characteristics of the functional
      ADC contrast using multiple degrees of IVIM weighting. It was found that the time
      course in the high b factor range lagged behind that of the low b factor range,
      indicating that the low b factor ADC contrast included contributions from the
      larger and faster moving arteries, and the smaller arterioles and capillaries
      downstream were reflected in the high b factor changes. These changes help
      confirm the arterial origin of the ADC contrast and offer a direction to improve
      the localization of activity to small vessel networks.

PMID- 15562491
TI  - Brain perfusion territory imaging applying oblique-plane arterial spin labeling
      with a standard send/receive head coil.
AB  - A new method for the selective spin labeling of left- or right-sided supplying
      arteries of the brain without the need for additional RF coils is demonstrated. A
      clinical 1.5 T scanner was used. The spatial selectivity of the labeling process
      is based on the limited coverage of the excitation field of a standard
      send/receive head coil together with an oblique positioning of the labeling
      plane. A computer simulation was used to optimize key labeling parameters under
      the condition of laminar flow. The validity of the computer model results was
      confirmed by MRI measurements with a flow model. For human studies, a double
      inversion continuous arterial spin labeling (CASL) sequence was modified to allow
      for arbitrary positioning of the labeling plane. The obtained perfusion-weighted
      images showed a clear delineation of the perfusion territories of the selected
      arteries in the anterior circulation of the brain and good gray/white matter
      contrast.

PMID- 15562492
TI  - New approach for correcting distortions in echo planar imaging.
AB  - A new method is described that can correct the distortions due to multiple off
      resonance effects in echo planar imaging, including those caused by B(0) field
      inhomogeneities, eddy currents, and gradient waveform imperfections. The proposed
      method uses a phase encoded acquisition and is as effective as the method of Chen
      and Wyricz (Chen and Wyricz, Magn Reson Med 1999;41:1206-1213) in correcting for
      distortions. Unlike Chen and Wyricz's approach, this new method works directly in
      distorted space and requires fewer scans. It also avoids the difficulties of
      phase unwrapping inherent in field mapping methods. Results using this new method
      with phantoms and human head scans at 3.0 T demonstrate the efficacy of the
      method in correcting distortions in both spin echo echo planar imaging (EPI) and
      gradient echo EPI.

PMID- 15562493
TI  - Self-navigated interleaved spiral (SNAILS): application to high-resolution
      diffusion tensor imaging.
AB  - A fat-saturated twice-refocused spin echo sequence was implemented on a GE Signa
      1.5-T whole-body system for diffusion-weighted imaging. Data were acquired using
      an analytically designed interleaved variable-density (VD) spiral readout
      trajectory. This flexible design algorithm allowed real-time prescription on the
      scanner. Each interleaf of the VD spiral oversampled the center of k-space. The
      oversampling provided an inherent motion compensation capability. The resultant
      diffusion-weighted images showed good quality without any retrospective motion
      correction. An iterated motion correction algorithm was developed to further
      reduce the signal cancellation artifact caused by motion-induced phase error. In
      this algorithm, a low-resolution phase map was estimated using the oversampled
      data in the center of k-space in order to correct for phase error in image space.
      In vivo diffusion tensor imaging (DTI) studies were performed on the brains of
      healthy volunteers. High-quality isotropic diffusion-weighted images, trace maps,
      and FA maps from axial, sagittal, and coronal slices were obtained using a VD
      spiral readout trajectory with matrix size 256 x 256. To our knowledge, this was
      also the first time in vivo 512 x 512 DTI results were reported.

PMID- 15562494
TI  - MRI measurement of hepatic magnetic susceptibility-phantom validation and normal
      subject studies.
AB  - A magnetic resonance (MR) imaging method with the potential for assessing hepatic
      iron overload from measurements of hepatic magnetic susceptibility in vivo is
      described. Using the blood in the portal and hepatic veins as an internal
      reference, this technique uses the orientation dependence of signal phase to
      measure the susceptibility of the liver parenchyma. Computer simulations were
      done to investigate the requirements on spatial resolution and contrast ratio
      between the vessels and the background liver tissue for data acquisition.
      Validation studies were conducted using tube-embedded gel phantoms doped with
      iron-dextran from 0 to 10 mg Fe/mL to mimic healthy and iron-overloaded livers.
      The phantom measurements were conducted without motion and flow, under
      respiration-like oscillatory motion, and with flow. Studies on six normal human
      subjects demonstrated excellent reproducibility and precision. All images were
      collected at 1.5 T using a 3D T(1)-weighted turbo field echo sequence for inflow
      MR angiographies with full flow compensation and capable of cardiac
      synchronization, navigator gating, and motion correction.

PMID- 15562495
TI  - Q-ball imaging.
AB  - Magnetic resonance diffusion tensor imaging (DTI) provides a powerful tool for
      mapping neural histoarchitecture in vivo. However, DTI can only resolve a single
      fiber orientation within each imaging voxel due to the constraints of the tensor
      model. For example, DTI cannot resolve fibers crossing, bending, or twisting
      within an individual voxel. Intravoxel fiber crossing can be resolved using q
      space diffusion imaging, but q-space imaging requires large pulsed field
      gradients and time-intensive sampling. It is also possible to resolve intravoxel
      fiber crossing using mixture model decomposition of the high angular resolution
      diffusion imaging (HARDI) signal, but mixture modeling requires a model of the
      underlying diffusion process.Recently, it has been shown that the HARDI signal
      can be reconstructed model-independently using a spherical tomographic inversion
      called the Funk-Radon transform, also known as the spherical Radon transform. The
      resulting imaging method, termed q-ball imaging, can resolve multiple intravoxel
      fiber orientations and does not require any assumptions on the diffusion process
      such as Gaussianity or multi-Gaussianity. The present paper reviews the theory of
      q-ball imaging and describes a simple linear matrix formulation for the q-ball
      reconstruction based on spherical radial basis function interpolation. Open
      aspects of the q-ball reconstruction algorithm are discussed.

PMID- 15562496
TI  - In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance
      imaging in transgenic mice without a contrast agent.
AB  - One of the cardinal pathologic features of Alzheimer's disease (AD) is the
      formation of senile, or amyloid, plaques. Transgenic mice have been developed
      that express one or more of the genes responsible for familial AD in humans.
      Doubly transgenic mice develop "human-like" plaques, providing a mechanism to
      study amyloid plaque biology in a controlled manner. Imaging of labeled plaques
      has been accomplished with other modalities, but only MRI has sufficient spatial
      and contrast resolution to visualize individual plaques noninvasively. Methods to
      optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a
      spin echo sequence based on adiabatic pulses are described. Preliminary results
      indicate that a spin echo acquisition more accurately reflects plaque size, while
      a T2* weighted gradient echo sequence reflects plaque iron content, not plaque
      size. In vivo MRI-ex vivo MRI-in vitro histologic correlations are provided.
      Histologically verified plaques as small as 50 microm in diameter were visualized
      in living animals. To our knowledge this work represents the first demonstration
      of noninvasive in vivo visualization of individual AD plaques without the use of
      a contrast agent.

PMID- 15562497
TI  - Comparison of arterial spin labeling and first-pass dynamic contrast-enhanced MR
      imaging in the assessment of pulmonary perfusion in humans: the inflow spin
      tracer saturation effect.
AB  - The flow-sensitive alternating inversion recovery (FAIR) and the first-pass
      dynamic contrast-enhanced MR imaging (CE-MRI) techniques have both been shown to
      be effective in the assessment of human pulmonary perfusion. However, no
      comprehensive comparison of the measurements by these two methods has been
      reported. In this study, healthy adults were recruited, with FAIR and CE-MRI
      performed for an estimation of the relative pulmonary blood flow (rPBF). Regions
      of interest were encircled from the right and left lungs, with right-to-left rPBF
      ratios calculated. Results indicated that, on posterior coronal slices, the rPBF
      ratios obtained with the FAIR technique agreed well with CE-MRI measurements
      (mean difference = -0.02, intraclass correlation coefficient RI = 0.78, 95%
      confidence interval = [0.67, 0.86]). On middle coronal slices, however, FAIR
      showed a substantially lower rPBF by up to 43% in the right lung compared with CE
      MRI (mean difference = -0.38, RI = 0.34, 95% confidence interval = [-0.09,
      0.68]). The location-dependent discrepancy between measurements by FAIR and CE
      MRI methods is attributed to tracer saturation effects of arterial inflow when
      the middle coronal slice contains the in-plane-oriented right pulmonary artery,
      whereas the left lung rPBF is less affected due to oblique orientation of the
      left pulmonary artery. Intrasequence comparison on additional subjects using FAIR
      at different slice orientations supported the above hypothesis. It is concluded
      that FAIR imaging for pulmonary perfusion in the coronal plane provides
      equivalent rPBF information with CE-MRI only in the absence of tracer saturation
      effects; hence, FAIR should be carefully exercised to avoid misleading
      interpretations.

PMID- 15562499
TI  - T2rho-weighted contrast in MR images of the human brain.
AB  - In this work, the feasibility of using T2rho weighting as an MR contrast
      mechanism is evaluated. Axial images of a human brain were acquired using a
      single-slice spin-lock T2rho-weighted pulse sequence and compared to analogous T2
      weighted images of the same slice. The contrast between white matter and gray
      matter in T2rho-weighted images was approximately 40% greater than that from T2
      weighted data. These preliminary data suggest that the novel contrast mechanism
      of T2rho can be used to yield high-contrast T2-like images.

PMID- 15562500
TI  - Shell growth and chamber formation of aquarium-reared Nautilus pompilius
      (Mollusca, Cephalopoda) by X-ray analysis.
AB  - Observations on the growth rate of aquarium maintained Nautilus pompilius in
      different developmental stages, i.e. juveniles (shell length about 8.75 cm), late
      juveniles (approximately 10 cm), and early adolescent (approximately 13.5 cm),
      indicate that this species is fully grown at an age of 7.3-8 years. The age
      calculations are based on two different computations: (1) the measurement of the
      increase of the shell length per day and (2) the formation of new septa in time
      intervals of 150+/-5 days, as demonstrated by X-ray analyses. After N. pompilius
      hatches, its shell grows about 139 mm to reach full growth and approximately 28
      septa are formed. With an increase of the shell length of 0.052 mm per day, it
      takes about 2,673 days (7.3 years) to reach maturity. Provided that the process
      of chamber formation follows an exponential function, these computations result
      in approximately 2,925 days (8 years) to reach full maturity. Supposing that N.
      pompilius may live for several years after onset of maturity like Nautilus
      belauensis, the total life span for this species may exceed 11-12 years.

PMID- 15562501
TI  - Cerebral pyruvate carboxylase flux is unaltered during bicuculline-seizures.
AB  - Glutamine synthesis in the astroglia reflects the sum of neurotransmitter cycling
      (glutamate and gamma-aminobutyric acid [GABA]) and de novo synthesis
      (anaplerosis), the latter catalyzed by pyruvate carboxylase. Previous studies
      have shown that the glutamate plus GABA cycling flux is correlated strongly with
      neuronal activity; however, the relationship between pyruvate carboxylase flux
      and neuronal activity is not known. In this study, pyruvate carboxylase flux was
      assessed during intravenous infusion of [2-(13)C]glucose using localized (1)H
      [(13)C] NMR spectroscopy at 7 Tesla in vivo in halothane-anesthetized and
      ventilated adult Wistar rats during 85 min of bicuculline-induced seizures (1
      mg/kg, intravenously) and in nontreated controls. During seizures, concentrations
      of lactate, alanine, glutamine, GABA, and succinate increased whereas glutamate
      and aspartate decreased such that the decrease in glutamate plus aspartate
      equaled the increase in glutamine plus GABA. Pyruvate carboxylase flux was
      assessed by the sum of [2-(13)C] and [3-(13)C] of glutamine and glutamate
      (Glx(2+3)) labeling during [2-(13)C]glucose infusion. During seizures the initial
      rate of Glx(2+3) synthesis (0.069 +/- 0.013 micromol/g/min) was not significantly
      different (P = 0.68) from that of the controls (0.059 +/- 0.010 micromol/g/min),
      indicating that anaplerotic flow through pyruvate carboxylase was unaltered.
      Intense neuronal activation of seizures did not seem to increase anaplerosis
      through pyruvate carboxylase, despite the substantial increase in neuronal
      activity and glutamate/glutamine cycling shown in a previous study (Patel et al.,
      2004b).

PMID- 15562502
TI  - Burkitt lymphoma in a child with Joubert syndrome.
AB  - Joubert syndrome is a rare disorder, characterized by hypoplasia, or aplasia of
      the cerebellar vermis, hypotonia, ataxia, and psychomotor retardation. The
      molecular basis underlying the disease is still unknown. There are various
      syndromes, which are associated with malignancies. Previously known associations
      between Joubert syndrome and tumors, are benign soft tissue tumors of the tongue
      and laryngeal lymphangioma. This report describes a 17-year-old boy known with
      Joubert syndrome, who was diagnosed with Burkitt lymphoma. The boy received
      chemotherapy, which successfully induced complete remission.

PMID- 15562503
TI  - Genital structures in the entelegyne widow spider Latrodectus revivensis
      (Arachnida; Araneae; Theridiidae) indicate a low ability for cryptic female
      choice by sperm manipulation.
AB  - The female genital structures of the entelegyne spider Latrodectus revivensis are
      described using semithin sections and scanning electron microscopy. Apart from
      the tactile hairs overhanging the opening of the atrium, the contact zones of the
      female epigynum are devoid of any sensilla, indicating that the female does not
      discriminate in favor or against males due to their genital size or stimulation
      through copulatory courtship. The dumb-bell shape and the spatial separation of
      the entrance and the exit of the paired spermathecae suggest that they are
      functionally of the conduit type. Not described for other entelegyne spiders so
      far, the small fertilization ducts originating from the spermathecae of each side
      lead to a common fertilization duct that connects the spermathecae to the uterus
      externus. During oviposition, it is most likely that spermatozoa are
      indiscriminately sucked out of the spermathecal lumina by the low pressure
      produced by the contraction of the muscle extending from the epigynal plate to
      the common fertilization duct. As no greater amounts of secretion are produced by
      the female during oviposition, and no activated sperm are present within the
      female genital tract, the secretion produced by the spermathecal epithelium does
      not serve in displacement or (selective) activation of spermatozoa. These
      findings suggest that female L. revivensis are not able to exert cryptic female
      choice by selectively choosing spermatozoa of certain males.

PMID- 15562504
TI  - Phenotype of cerebellar glutamatergic neurons is altered in stargazer mutant mice
      lacking brain-derived neurotrophic factor mRNA expression.
AB  - Brain-derived neurotrophic factor (BDNF) influences neuronal survival,
      differentiation, and maturation. More recently, its role in synapse formation and
      plasticity has also emerged. In the cerebellum of the spontaneous recessive
      mutant mouse stargazer (stg) there is a specific and pronounced deficit in BDNF
      mRNA expression. BDNF protein levels in the cerebellum as a whole are reduced by
      70%, while in the granule cells (GCs) there is a selective and near total
      reduction in BDNF mRNA expression. Recently, we published data demonstrating that
      inhibitory neurons in the cerebella of stgs have significantly reduced levels
      (approximately 50%) of gamma-aminobutyric acid (GABA) and fewer, smaller
      inhibitory synapses compared to wildtype (WT) controls. Our current
      investigations indicate that the stargazer mutation has an even more pronounced
      effect on the phenotype of glutamatergic neurons in the cerebellum. There is a
      profound decrease in the levels of glutamate-immunoreactivity (up to 77%) in stg
      compared to WT controls. The distribution profile of presynaptic vesicles is also
      markedly different: stgs have proportionally fewer docked vesicles and fewer
      vesicles located adjacent to the active zone ready to dock than WTs. Furthermore,
      the thickness of the postsynaptic density (PSD) at mossy fiber-granule cell (MF
      GC) and parallel fiber-Purkinje cell (PF-PC) synapses is severely reduced (up to
      33% less than WT controls). The number and length of excitatory synapses,
      however, appear to be relatively unchanged. It is possible that at least some of
      theses changes in phenotype are directly attributable to the lack of BDNF in the
      cerebellum of the stg mutant.

PMID- 15562505
TI  - Morphometric and anatomic study of the forelimb of the dog.
AB  - The object of this study was to obtain the anatomic and morphometric data
      required for biomechanical analyses of the forelimb in dogs. Following the
      euthanasia of four healthy, adult, crossbred dogs, 44 muscles of the right
      forelimb were identified and meticulously removed. Morphometric data for all
      muscles were collected and physiologic cross-sectional areas (PCSA) and
      architectural indices (AI) were calculated. The coordinates of the origin and
      insertion of each muscle were determined using orthogonal, right-handed
      coordinate systems embedded in the scapula, humerus, and radius-ulna. The PCSA
      and AI were calculated for all the muscles and coordinates for the origins and
      insertions of these muscles were determined. Results provide the morphometric and
      anatomic data necessary for three-dimensional biomechanical studies of the
      forelimb in dogs.

PMID- 15562506
TI  - Activation of the parabrachio-amygdaloid pathway by immune challenge or spinal
      nociceptive input: a quantitative study in the rat using Fos immunohistochemistry
      and retrograde tract tracing.
AB  - Peripheral nociceptive stimulation results in activation of neurons in the
      pontine parabrachial nucleus (PB) of rats. Electrophysiological studies have
      suggested that noxiously activated PB neurons project to the amygdala,
      constituting a potential pathway for emotional aspects of pain. In the present
      study we examined this hypothesis by combining retrograde tract tracing with Fos
      immunohistochemistry. Cholera toxin subunit B was injected into the amygdala of
      rats. After a minimum of 48 hours the rats were given a subcutaneous injection of
      100 microl of 5% formalin into one hindpaw and killed 60-90 minutes later. A
      dense aggregation of retrogradely labeled neurons was seen in the external
      lateral PB. Fos-expressing neurons were present preferentially in the central,
      dorsal, and superior lateral subnuclei as well as in the lateral crescent area,
      as described previously. There was little overlap between the retrogradely
      labeled and Fos-expressing populations and double-labeled neurons were rare. In
      contrast, systemic immune challenge by intravenous injection of bacterial wall
      lipopolysaccharide resulted in a Fos expression that overlapped the retrograde
      labeling in the external lateral PB, and many double-labeled neurons were seen.
      While these data provide direct functional anatomical evidence that nociceptive
      information from the hindlimb is relayed to the amygdala via the parabrachial
      nucleus, the number of parabrachio-amygdaloid neurons involved is small.
      Considering the widespread activation of parabrachio-amygdaloid neurons by a
      variety of visceral and humoral stimuli, the parabrachio-amygdaloid pathway thus
      appears to be more involved in the mediation of information related to viscerally
      and humorally elicited activity than in transmission of spinal nociceptive
      inputs.

PMID- 15562507
TI  - Evolutionary conservation of the egr-1 immediate-early gene response in a
      teleost.
AB  - Immediate-early gene expression is a key part of a neuron's response to
      behaviorally relevant stimuli and, as a result, localization of immediate-early
      gene expression can be a useful marker for neural activity. We characterized the
      immediate-early gene egr-1 (also called zif268, NGFI-A, krox-24, ZENK) in the
      teleost Astatotilapia (Haplochromis) burtoni. We compared the A. burtoni egr-1
      predicted protein sequence to that of other vertebrates, characterized its gene
      expression time course, and localized its induced expression throughout the
      brain. The A. burtoni egr-1 predicted protein shared putative functional domains
      with egr-1 of other vertebrates and shared 81% sequence similarity with zebrafish
      and 66% with mouse. We identified distinct mammalian and teleost inserts rich in
      serine residues within one activation domain, suggesting convergent responses to
      selection pressures to increase the number of serine residues in this region.
      Functionally, we found that A. burtoni egr-1 gene expression peaked near 30
      minutes after pharmacological stimulation and thereby displayed the transient
      expression above basal levels characteristic of egr-1 expression in birds and
      mammals. Finally, we observed distinct patterns of egr-1 gene induction in the
      brain by natural and pharmacological stimuli. Unstimulated males had very low
      expression levels of egr-1, whereas males stimulated by their normal environment
      showed higher levels of expression specific to particular brain regions. Males
      injected with a glutamate receptor agonist also had region-specific induction of
      egr-1 expression. We conclude that the egr-1 immediate-early gene response is
      evolutionarily conserved and will, therefore, be useful for identifying
      functional neural responses in nontraditional model species.

PMID- 15562508
TI  - Retrograde double-labeling study of common afferent projections to the dorsal
      raphe and the nuclear core of the locus coeruleus in the rat.
AB  - Common afferent projections to the dorsal raphe (DR) and locus coeruleus (LC)
      nuclei were analyzed in the rat by making paired injections of retrograde
      tracers, gold-conjugated and inactivated wheatgerm agglutinin-horseradish
      peroxidase (WGA-apo-HRP-gold) and Fluorogold (FG), into the DR and the nuclear
      core of the LC. Our results demonstrate that the largest number of double-labeled
      neurons was located at various preoptic regions including medial preoptic area,
      lateral preoptic nucleus, and ventrolateral preoptic nucleus. The majority of
      labeled cells were also observed at the lateral hypothalamus, where the number of
      labeled cells was comparable to that of neurons at the medial preoptic area or
      lateral preoptic nucleus. A few double-labeled cells were observed at various
      hypothalamic regions including anterior, medial tuberal, posterior, and arcuate
      nuclei, as well as mesencephalic areas including substantia nigra compacta and
      ventrolateral/lateral periaqueductal gray matter. Cells were also observed at
      prelimbic/infralimbic prefrontal cortices, diagonal band of Broca, bed nucleus of
      stria terminalis, and pontine/medullary regions including various raphe nuclei,
      Barrington's nucleus, gigantocellularis, paragigantocellularis, prepositus
      hypoglossi, subcoeruleus, and dorsomedial tegmental area. Although
      electrophysiological studies need to be performed, a large number of double
      labeled neurons located at preoptic regions as well as lateral hypothalamus might
      have their major role in simultaneous control over these monoaminergic nuclei as
      a means of influencing various sleep and arousal states of the animal. Double
      labeled cells at the other locations might be positioned to influence a variety
      of other functions such as analgesia, cognition, and stress responses.

PMID- 15562509
TI  - Morphological identification of ganglion cells expressing the alpha subunit of
      type II calmodulin-dependent protein kinase in the macaque retina.
AB  - Expression of the alpha subunit of type II calmodulin-dependent protein kinase
      (alphaCamKII) distinguishes the koniocellular neurons of the primate lateral
      geniculate nucleus (LGN) from the primary parvo- and magnocellular neurons, but
      whether the same neurochemical signature distinguishes the retinal ganglion cells
      providing them input is not known. We find that, in the retina, alphaCamKII
      expression also differentiates two primary groups of ganglion cell, both
      characterized by broad, sparsely branching dendritic trees and cell bodies
      intermediate in size between the parvo- and magnocellular-projecting ganglion
      cells. Cells in the first group have three or four primary dendrites, a thick
      axon, and a rounded cell body and likely are made up of multiple types. In
      contrast, ganglion cells in the second group demonstrate a highly regular
      morphology, with strictly two primary dendrites and a thinner axon emanating from
      a smaller, elliptical cell body. This cell resembles the "large sparse" ganglion
      cell identified by others in retrograde labeling from the LGN and represents
      about 2% of all ganglion cells. In the optic nerve, alphaCamKII+ axons are also
      intermediate in size and form a bimodal distribution, correlating with the axonal
      sizes of the two groups of ganglion cell. For the LGN, we describe a group of
      alphaCamKII+ axon terminals with morphology consistent with terminals from
      retinal ganglion cells. These terminals form long, filamentous contacts with
      alphaCamKII+ relay cells and increase in frequency from the dorsal to the ventral
      koniocellular regions. Our results indicate that ganglion cells expressing
      alphaCamKII represent multiple projections to the brain, at least one of which
      provides input to one or more koniocellular regions of the LGN.

PMID- 15562510
TI  - Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia.
AB  - Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the
      brainstem neurons is diagnostic for Parkinson's disease, whereas if this process
      also occurs in the cortical neurons, it is considered pathognomonic for dementia
      with Lewy bodies. However, the link between alpha-synuclein incorporation into
      inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified.
      Another important issue of the pathogenetic puzzle is to understand where alpha
      synuclein pathology begins and how it progresses in the brain. To study this, we
      collected all cases from autopsy material (N = 904) that had alpha-synuclein
      pathology in the dorsal motor nucleus of vagus, substantia nigra, and/or basal
      forebrain nuclei. In this way, our study has a unique design because the
      selection of material is entirely based on the presence of alpha-synuclein
      pathology regardless of clinical phenotype. Retrospective clinical assessment
      then showed that only 32 (30%) of 106 alpha-synuclein-positive cases were
      diagnosed with a neurodegenerative disorder. The distribution or load of alpha
      synuclein pathology did not permit a dependable postmortem diagnosis of
      extrapyramidal symptoms or cognitive impairment. Some neurologically unimpaired
      cases had a reasonable burden of alpha-synuclein pathology in both brainstem and
      cortical areas, suggesting that alpha-synuclein-positive structures are not
      definite markers of neuronal dysfunction.

PMID- 15562511
TI  - Organization of hypocretin/orexin efferents to locus coeruleus and basal
      forebrain arousal-related structures.
AB  - Hypocretin/orexin neurons give rise to an extensive projection system, portions
      of which innervate multiple regions associated with the regulation of behavioral
      state. These regions include the locus coeruleus, medial septal area, medial
      preoptic area, and substantia innominata. Evidence indicates that hypocretin
      modulates behavioral state via actions within each of these terminal fields. To
      understand better the circuitry underlying hypocretin-dependent modulation of
      behavioral state, the present study characterized the degree to which there
      exists: 1) lateralization of hypocretin efferents to basal forebrain and
      brainstem arousal-related regions, 2) topographic organization of basal forebrain
      and brainstem-projecting hypocretin neurons, and 3) collateralization of
      individual hypocretin neurons to these arousal-related terminal fields. These
      studies utilized combined immunohistochemical identification of hypocretin
      neurons with single or double retrograde tracing from the locus coeruleus, medial
      preoptic area, medial septal area, and substantia innominata. Results indicate
      that approximately 80% of hypocretin efferents to basal forebrain regions project
      ipsilaterally, whereas projections to the locus coeruleus are more bilateral
      (65%). There was a slight preference for basal forebrain-projecting hypocretin
      neurons to be distributed within the medial half of the hypocretin cell group. In
      contrast, hypocretin neurons projecting to the locus coeruleus were located
      primarily within the dorsal half of the hypocretin cell group. Finally, a large
      proportion of hypocretin neurons appear to project simultaneously to at least two
      of the examined terminal fields. These latter observations suggest coordinated
      actions of hypocretin across multiple arousal-related regions.

PMID- 15562512
TI  - Crystal structure of the conserved hypothetical protein MPN330 (GI: 1674200) from
      Mycoplasma pneumoniae.

PMID- 15562513
TI  - An alphaTropomyosin mutation alters dimer preference in nemaline myopathy.
AB  - Nemaline myopathy is a human neuromuscular disorder associated with muscle
      weakness, Z-line accumulations (rods), and myofibrillar disorganization. Disease
      causing mutations have been identified in genes encoding muscle thin filament
      proteins: actin, nebulin, slow troponin T, betaTropomyosin, and
      alphaTropomyosin(slow). Skeletal muscle expresses three tropomyosin (Tm) isoforms
      from separate genes: alphaTm(fast)(alphaTm, TPM1), betaTm (TPM2), and
      alphaTm(slow) (gammaTm, TPM3). In this article, we show that the level of betaTm,
      but not alphaTm(fast) protein, is reduced in human patients with mutations in
      alphaTm(slow) and in a transgenic mouse model of alphaTm(slow)(Met9Arg) nemaline
      myopathy. A postnatal time course of Tm expression in muscles of the mice
      indicated that the onset of alphaTm(slow)(Met9Arg) expression coincides with the
      decline of betaTm. Reduction of betaTm levels is independent of the degree of
      pathology (rods) within a muscle and is detected before the onset of muscle
      weakness. Thus, reduction in the level of betaTm represents an early clinical
      diagnostic marker for alphaTm(slow)-based mutations. Examinations of tropomyosin
      dimer formation using either recombinant proteins or sarcomeric extracts show
      that the mutation reduces the formation of the preferred alpha/beta heterodimer.
      We suggest this perturbation of tropomyosin isoform levels and dimer preference
      alters sarcomeric thin filament dynamics and contributes to muscle weakness in
      nemaline myopathy.

PMID- 15562514
TI  - Food fortification with folic acid and rate of multiple births, 1994-2000.
AB  - BACKGROUND: Since fortification of cereal grain products with synthetic folic
      acid (FA) became mandatory in January 1998, women in the United States who have
      become pregnant have been exposed to a higher level of FA than women who became
      pregnant previously. Some studies have suggested that increased FA consumption
      might increase the risk of multiple gestation pregnancies. METHODS: Women who had
      a live birth in Kaiser Foundation Health Plan hospitals from January 1, 1994
      through December 31, 2000; all multiple births; and the use of ovulation-inducing
      drugs were ascertained from electronic databases. Medical records of a sample of
      women with multiple births who did not use ovulation-inducing drugs were reviewed
      to determine whether they used assisted reproductive technology. Exposure to FA
      fortified foods was based on date of delivery. RESULTS: The rate of multiple
      births increased from 13.6 to 14.8 per 1000 live births from 1994 through 2000.
      The percentage of women who had a multiple birth and who filled a prescription
      for an ovulation-inducing drug in the 12 months before delivery increased from a
      low of 6.6% in 1994 to a high of 14.9% in 2000. After excluding women using
      ovulation-inducing drugs, the increased rate of multiple births was no longer
      observed. CONCLUSIONS: While the rates of multiple births have increased since FA
      fortification became mandatory, this increase can be explained by the increased
      use of ovulation-inducing drugs. Our findings show no relationship between food
      fortification with FA and the rates of multiple births in this large, managed
      health care population.

PMID- 15562515
TI  - A generalized affine gap model significantly improves protein sequence alignment
      accuracy.
AB  - Sequence alignment underpins common tasks in molecular biology, including genome
      annotation, molecular phylogenetics, and homology modeling. Fundamental to
      sequence alignment is the placement of gaps, which represent character insertions
      or deletions. We assessed the ability of a generalized affine gap cost model to
      reliably detect remote protein homology and to produce high-quality alignments.
      Generalized affine gap alignment with optimal gap parameters performed as well as
      the traditional affine gap model in remote homology detection. Evaluation of
      alignment quality showed that the generalized affine model aligns fewer residue
      pairs than the traditional affine model but achieves significantly higher per
      residue accuracy. We conclude that generalized affine gap costs should be used
      when alignment accuracy carries more importance than aligned sequence length.

PMID- 15562516
TI  - Interaction interfaces of protein domains are not topologically equivalent across
      families within superfamilies: Implications for metabolic and signaling pathways.
AB  - Using a data set of aligned protein domain superfamilies of known three
      dimensional structure, we compared the location of interdomain interfaces on the
      tertiary folds between members of distantly related protein domain superfamilies.
      The data set analyzed is comprised of interdomain interfaces, with domains
      occurring within a polypeptide chain and those between two polypeptide chains. We
      observe that, in general, the interfaces between protein domains are formed
      entirely in different locations on the tertiary folds in such pairs. This
      variation in the location of interface happens in protein domains involved in a
      wide range of functions, such as enzymes, adapters, and domains that bind protein
      ligands, or cofactors. While basic biochemical functionality is preserved at the
      domain superfamily level, the effect of biochemical function on protein
      assemblies is different in these protein domains related by superfamily. The
      divergence between proteins, in most cases, is coupled with domain recruitment,
      with different modes of interaction with the recruited domain. This is in
      complete contrast to the observation that in closely related homologous protein
      domains, almost always the interaction interfaces are topologically equivalent.
      In a small subset of interacting domains within proteins related by remote
      homology, we observe that the relative positioning of domains with respect to one
      another is preserved. Based on the analysis of multidomain proteins of known or
      unknown structure, we suggest that variation in protein-protein interactions in
      members within a superfamily could serve as diverging points in otherwise
      parallel metabolic or signaling pathways. We discuss a few representative cases
      of diverging pathways involving domains in a superfamily.

PMID- 15562517
TI  - Protonation of trimipramine salts of maleate, mesylate and hydrochloride observed
      by 1H, 13C and 15N NMR spectroscopy.
AB  - Protonation of the tricyclic antidepressant drug trimipramine with maleic acid,
      methanesulfonic acid and hydrochloric acid was studied using 1H, 13C and 15N NMR
      spectroscopy at natural abundance. The effect of counter ions on the protonation
      was compared under identical conditions of solvent, concentration and temperature
      using homonuclear and heteronuclear one- and two-dimensional experiments.
      Differential protonation of the terminal tertiary amine nitrogen is determined
      from the indirect spin-spin couplings, chemical shifts, 13C relaxation data and
      variable-temperature experiments. In the maleate salt, only one of the acidic
      protons is involved in protonation, the other being associated with the anion
      moiety. 15N chemical shifts of the protonated nitrogens are nearly linearly
      related to the pK(a) of the constituent acid.

PMID- 15562518
TI  - Total assignment of 1H and 13C NMR spectra of the alkaloid 3,3-diisopentenyl-N
      methyl-2,4-quinoldione and novel reaction derivatives.
AB  - One- and two-dimensional NMR experiments were used for the unambiguous assignment
      of the 1H and 13C NMR chemical shifts of 3,3-diisopentenyl-N-methyl-2,4
      quinoldione and five novel reaction derivatives.

PMID- 15562519
TI  - A molecular dynamics study of the structural stability of HIV-1 protease under
      physiological conditions: the role of Na+ ions in stabilizing the active site.
AB  - HIV-1 protease is most active under weakly acidic conditions (pH 3.5-6.5), when
      the catalytic Asp25 and Asp25' residues share 1 proton. At neutral pH, this
      proton is lost and the stability of the structure is reduced. Here we present an
      investigation of the effect of pH on the dynamics of HIV-1 protease using MD
      simulation techniques. MD simulations of the solvated HIV-1 protease with the
      Asp25/25' residues monoprotonated and deprotonated have been performed. In
      addition we investigated the effect of the inclusion of Na(+) and Cl(-) ions to
      mimic physiological salt conditions. The simulations of the monoprotonated form
      and deprotonated form including Na(+) show very similar behavior. In both cases
      the protein remained stable in the compact, "self-blocked" conformation in which
      the active site is blocked by the tips of the flaps. In the deprotonated system a
      Na(+) ion binds tightly to the catalytic dyad shielding the repulsion between the
      COO(-) groups. Ab initio calculations also suggest the geometry of the active
      site with the Na(+) bound closely resembles that of the monoprotonated case. In
      the simulations of the deprotonated form (without Na(+) ions), a water molecule
      bound between the Asp25 Asp25' side-chains. This disrupted the dimerization
      interface and eventually led to a fully open conformation.

PMID- 15562520
TI  - NMR spectroscopic analysis of lotusine.
AB  - Lotusine, a soluble alkaloid, is one of the major constituents of the Chinese
      medicine Lotus Plumule, and has antihypertension and antibacterial activity. In
      order to confirm the structures reported in the literature by explicit 1H and 13C
      assignments, we applied a series of NMR experiments including 1H-1H COSY, HSQC
      and HMBC.

PMID- 15562522
TI  - HUPO (Human Proteome Organization) 3rd Annual World Congress. Beijing, China,
      October 25-27, 2004.

PMID- 15562521
TI  - Design of a data model for developing laboratory information management and
      analysis systems for protein production.
AB  - Data management has emerged as one of the central issues in the high-throughput
      processes of taking a protein target sequence through to a protein sample. To
      simplify this task, and following extensive consultation with the international
      structural genomics community, we describe here a model of the data related to
      protein production. The model is suitable for both large and small facilities for
      use in tracking samples, experiments, and results through the many procedures
      involved. The model is described in Unified Modeling Language (UML). In addition,
      we present relational database schemas derived from the UML. These relational
      schemas are already in use in a number of data management projects.

PMID- 15562523
TI  - Abstracts of the British Geriatrics Society Spring Meeting. 6-8 April 2004,
      Northern Ireland.

PMID- 15562524
TI  - Abstracts of the American Society of Hematology 46th Annual Meeting. December 4
      7, 2004, San Diego, California, USA.

PMID- 15562525
TI  - Abstracts of the American Society of Hematology 46th Annual Meeting. December 4
      7, 2004, San Diego, California, USA.

PMID- 15562526
TI  - Abstracts of the 3rd Annual AACR International Conference: Frontiers in Cancer
      Prevention Research. October 16-20, 2004, Seattle, Washington, USA.

PMID- 15562527
TI  - New classes of HIV inhibitors raise promise for future treatments. HIV experts
      discuss the most intriguing research.
AB  - From CCR5 inhibitors to tweaking the body's immune response, new possibilities
      exist for HIV treatment, and researchers say they are optimistic that many of
      these will be effective warriors against HIV disease.

PMID- 15562528
TI  - Assembly inhibitors offer hope for future treatment. Researchers explain their
      work in this area.
AB  - Early research into what are being called assembly inhibitors may offer a
      nontraditional approach a new line of defense against HIV in decades to come.

PMID- 15562529
TI  - Study finds depression higher among inpatients. Motor functioning problems also
      may play role.
AB  - Researchers in New Orleans found that depression is one of the key differences
      between HIV patients who need hospitalization and those who don't.

PMID- 15562530
TI  - Attention HIV doctors: you're doing a good job. Study finds racial differences in
      responses.
AB  - HIV patients surveyed about their medical care report overall satisfaction,
      including those who say they have gotten worse, a new study says.

PMID- 15562531
TI  - Access to affordable drugs hinges on competition. Study notes lowest prices in
      India, South Africa.
AB  - A new study finds that developing nations with greater market competition for
      antiretrovirals and more generic producers tend to have cheaper antiretroviral
      drugs available through the private sector.

PMID- 15562532
TI  - Internet use for dating tied to sexual risk taking. Nearly 1 in 5 surveyed have
      looked for dates on-line.
AB  - Using the Internet to find sex partners is common among the general population,
      and not just about homosexuals, researchers have found.

PMID- 15562533
TI  - Breast-feeding guidelines: an implementation puzzle. Experts say there is no easy
      solution.
AB  - The WHO is attempting to provide guidance in the thorny dilemma faced by many HIV
      positive women: should they breast-feed and risk transmission to their infant, or
      should they use substitute nutrition which may place their infant at greater risk
      of dying within the first year?

PMID- 15562534
TI  - Programs aim to reduce MTCT in poor nations. Here's a look at what can and is
      being done.
AB  - A number of programs have developed strategies for reducing the risk among women
      in poor nations who face the breast-feeding vs. substitute nutrition quandary.

PMID- 15562535
TI  - HCV rates outpacing HIV in NYC, study finds. New IDUs had greatest HCV burden.
AB  - New York investigators have found, to their surprise, that high incidence of HCV
      did not necessarily mean high rates of HIV. The findings show that people who
      have started injecting drugs have a higher HCV rate.

PMID- 15562536
TI  - Flu vaccine. Vaccine shortage threatens HIV-positive.

PMID- 15562537
TI  - Election. Debates show top officials ill-advised about U.S. AIDS epidemic.

PMID- 15562539
TI  - Disclosure. Threat of disclosing man's serostatus unacceptable behavior.

PMID- 15562538
TI  - New Medicare guidelines fail to protect those with HIV/AIDS.

PMID- 15562540
TI  - Unwarranted exposure to AIDS insufficient to prevail in claim.

PMID- 15562541
TI  - Election. Cheney acknowledges economic threat posed by HIV/AIDS in debate.

PMID- 15562542
TI  - Discrimination. Lambda: doctor's failure to treat HIV-positive patient illegal.

PMID- 15562543
TI  - Immigration. Doctor who certified immigrants as HIV-negative sentenced.

PMID- 15562544
TI  - Custody. Termination of HIV-positive mother's parental rights affirmed.

PMID- 15562545
TI  - Insurance. False allegation of preexisting HIV backfires on insurer.

PMID- 15562546
TI  - Disability. Officer who contracted HIV through bite is granted benefits.

PMID- 15562547
TI  - Jails. Fear of HIV transmission is costly to man who bit deputy.

PMID- 15562548
TI  - Disease prevention. Texas officials sue HIV-positive woman to compel treatment.

PMID- 15562549
TI  - National Latino AIDS awareness day aims to reduce HIV rates.

PMID- 15562550
TI  - [Spondylocostal dysostosis: a rare genetic disease].
AB  - Spondylocostal dysostoses represent a group of very rare genetic disorders,
      characterised by vertebral and costal segmentation defects, sometimes accompanied
      by visceral malformations. The major gene involved is DLL3, on chromosome 19. A
      mutation may lead to a somitogenesis defect, with segmentation defect of axial
      skeleton and deformations. Depending on the nature of the mutation of DLL3,
      spondylocostal dysostosis is transmitted as an autosomal dominant (less severe)
      or autosomal recessive trait (often more severe, but non lethal). Spondylocostal
      dysostoses must not to be confused with the Jarcho-Levin spondylothoracic
      dysostosis, a severe, autosomal recessive syndrome. Its most typical aspect is
      the crab-like appearance of the rib cage leading to major respiratory disorders.
      Death, due to respiratory insufficiency, usually occurs before the age of two,
      most often during the first few months. At this time, guidelines for treatment do
      not exist. We report a case of spondylocostal dysosotosis in a patient born to
      consanguineous turkish parents, and review the clinical and genetic data on that
      group of skeletal disorders.

PMID- 15562551
TI  - Improved borate method for the rapid distinction of glucosamine and galactosamine
      in an exopolysaccharide produced by Citrobacter sp.
AB  - An improved borate method for the quantitative distinction of glucosamine (GlcN)
      and galactosamine (GalN) in a mixture is presented which is based on the Elson
      Morgan method with addition of sodium borate to differentiate colour formation by
      the two hexosamines. The r2 value and maximum deviation of the method based on
      calculations derived in this study were 0.9979 and 5.1 %, respectively. Using
      this method, the GlcN/GalN ratio in an exopolysaccharide (EPS) produced by
      Citrobacter sp. was found to change with time during the production process, with
      a maximum value at 9.8:1.

PMID- 15562552
TI  - Bronchioloalveolar carcinoma masquerading as pneumonia.
AB  - Bronchioloalveolar carcinoma (BAC) is a relatively rare adenocarcinoma that
      typically arises in the lung periphery and grows along alveolar walls, without
      destroying the lung parenchyma. It is often multicentric and may arise from a
      previously stable scar. Because the parenchyma is preserved and because BAC may
      arise simultaneously in multiple lobes, the chest radiograph and symptoms (cough,
      chest pain, and sputum production) may be indistinguishable from pneumonia or
      other noninfectious inflammatory processes (eg, hypersensitivity pneumonitis or
      bronchiolitis obliterans). The clinician should suspect BAC if what otherwise
      appears to be pneumonia lacks fever or leukocytosis or does not respond to
      antibiotics. BAC accounts for 2.6-4.3 % of all lung cancers. On a radiograph, BAC
      often appears as a solitary nodule, but may also appear as a patchy, lobar or
      multilobar infiltrates, often with air bronchograms indistinguishable from
      pneumonia. Positron-emission tomography does not help distinguish BAC from
      pneumonia. Among BAC patients, 62% present without symptoms and with only an
      abnormal radiograph, whereas 38% present with symptoms of cough, chest pain, and
      sputum production. Bronchoscopy is usually normal. Preoperative diagnosis with
      transbronchial biopsy, bronchoscopic cytology examination, or expectorated sputum
      cytology is more common with the diffuse or multicentric forms. Cure depends on
      complete resection. A trial of antibiotics and reassessment of clinical findings
      is a reasonable approach, but biopsy or cytology is the only means of ruling in
      malignancy and ruling out other etiologies, so biopsy should always be considered
      when a presumed pneumonia does not respond to antibiotics. I saw a 61-year-old
      man whose initial diagnosis was pneumonia. He took a 10-day course of oral
      azithromycin, but his symptoms and chest radiograph were unchanged. A tomogram
      showed interstitial prominence and peripheral air-space disease in the right
      upper and lower lobes. Transbronchial biopsy of the right upper lobe showed Clara
      cells, with substantial atypia and various nuclear-cytoplasmic ratios. The
      underlying pulmonary architecture was preserved and no invasive component was
      seen. The diagnosis was changed to nonmucinous BAC. Pneumonectomy was successful
      and he was cancer-free for about 10 months, after which the cancer returned and
      from which he eventually died.

PMID- 15562553
TI  - Transtracheal oxygen: not exactly a "novel" technology.

PMID- 15562554
TI  - Medical devices; clinical chemistry and clinical toxicology devices;
      classification of newborn screening test systems for amino acids, free carnitine,
      and acylcarnitines using tandem mass spectrometry. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying newborn screening test
      systems for amino acids, free carnitine, and acylcarnitines using tandem mass
      spectrometry into class II (special controls). The special control that will
      apply to the device is the guidance document entitled "Class II Special Controls
      Guidance Document: Newborn Screening Test Systems for Amino Acids, Free
      Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry." The agency is
      taking this action in response to a petition submitted under the Federal Food,
      Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of
      1976, the Safe Medical Devices Act of 1990, the Food and Drug Administration
      Modernization Act of 1997, and the Medical Device User Fee and Modernization Act
      of 2002. The agency is classifying the device into class II (special controls) in
      order to provide a reasonable assurance of safety and effectiveness of the
      device. Elsewhere in this issue of the Federal Register, FDA is publishing a
      notice of availability of a guidance document that is the special control for
      this device.

PMID- 15562555
TI  - Current good tissue practice for human cell, tissue, and cellular and tissue
      based product establishments; inspection and enforcement. Final rule.
AB  - The Food and Drug Administration (FDA) is requiring human cell, tissue, and
      cellular and tissue-based product (HCT/P) establishments to follow current good
      tissue practice (CGTP), which governs the methods used in, and the facilities and
      controls used for, the manufacture of HCT/Ps; recordkeeping; and the
      establishment of a quality program. The agency is also issuing new regulations
      pertaining to labeling, reporting, inspections, and enforcement that will apply
      to manufacturers of those HCT/Ps regulated solely under the authority of the
      Public Health Service Act (PHS Act), and not as drugs, devices, and/or biological
      products. The agency's actions are intended to improve protection of the public
      health while keeping regulatory burden to a minimum, which in turn would
      encourage significant innovation.

PMID- 15562556
TI  - Ability of lymphoscintigraphy to direct sentinel node biopsy in the clinically NO
      check for patients with head and neck squamous cell carcinoma; a prospective
      study (preliminary results).
AB  - Detection of metastasis involvement of lymph nodes is essential for management
      and prognostic evaluation in most cancer cases. The success of lymphatic mapping
      depends on identifying the sentinel lymph node(s) draining the primary tumour. In
      this preliminary study we prospectively evaluated the feasibility of sentinel
      node radio localisation in head and neck squamous cell carcinoma N0 stage to gain
      insight as to whether the sentinel lymph node (SLN) could be prognostic of
      regional metastasis disease or not. In 14 patients with squamous cell carcinoma
      of the head and neck region preoperative lymphoscintigraphy (LSG) mapping of the
      tumour was performed after subcutaneous injection of 22 to 30 MBq of Tc99m
      labelled sulfur colloid. SLN was detected and localised by LSG in all patients
      with a gamma camera and a hand-held gamma probe. All the patients underwent
      surgery SLN and cervical nodes dissection. Six SLNs for five patients revealed
      occult metastasis disease. No skip metastasis were found in the 9 necks with
      negative SLN analysis. The results of this preliminary study are encouraging.
      They showed that SLN in squamous cell carcinoma of the head and neck N0 is
      accurately feasible and could predict the presence of occult metastasis.
      Nevertheless, more data are needed to validate these results.

PMID- 15562557
TI  - Modulation of Growth Factor response in brain tumors by complex carbohydrates.
AB  - It is well established that growth factors and their receptors are overexpressed
      in brain tumors and play a key role in tumor cell proliferation. Glycoconjugate
      molecules expressed at the plasma membrane of mammalian cells have been also
      reported to be associated with tumor progression. Growth factor receptors and
      glycoconjugate molecules are able to interact with each other and this
      interaction usually results in modulation of growth factor receptor mediated
      signaling and the biological function of the cell. This review addresses the
      expression of both growth factor receptors and glycoconjugates molecules in the
      brain and brain tumors. The mechanism by which these two entities interact with
      each other and the consequences of their interaction on the biological function
      of tumor cell are also discussed. Glycoconjugate molecules seems to act more
      specifically on growth factor receptor signaling pathways than most of tyrosine
      kinase inhibitors. The use of glycoconjugates or their derivatives may represent
      a new approach to modulate the proliferative behavior of tumors that overexpress
      growth factor receptors such as brain tumors.

PMID- 15562558
TI  - The analysis of correlations between drug resistance and clinical/laboratory
      measures found in a group of children with all treated by ALL-BFM 90 protocol.
AB  - This study was designed to assess the predictive value of an MTT (3-[4,5
      dimethylthiazol-2,5-diphenyl] tetrazolium bromide) in vitro assay for the
      evaluation of leukemic cell resistance/sensitivity to cytotoxic drugs, and to
      compare these results with clinical and laboratory parameters in cases of
      childhood acute lymphoblastic leukemia (ALL).The chemoresistance of leukemic
      cells was ascertained by means of an MTT assay in 32 previously untreated
      children with ALL. The children were treated using the protocol ALL-BFM 90.
      Statistical correlations were made between in vitro drug resistance to anti
      cancer drugs: prednisolone (PRED), vincristine (VCR),daunorubicin (DNR),
      etoposide (VP-16) and cytosine arabinoside (ARA-C) and in vivo clinical and
      laboratory parameters: age, sex, risk factor (RF), leukocytes (WBC)and absolute
      number of blast cells (BC) at diagnosis (BC0), BC at day 8 (BC8), the percentage
      of blast cells in bone marrow at day 15 (BM15) and at day 33 (BM33),and leukocyte
      surface antigens CD3, CD4, CD5, CD8, CD10, CD19, CD20, HLADR.

PMID- 15562559
TI  - Cryopreservation with hydroxyethylstarch (HES) + dimethylsulfoxide (DMSO) gives
      better results than DMSO alone.
AB  - This study compares the cryopreservation of PBSC by means of HES 3% + DMSO 5% ina
      mechanical freezer with the cryopreservation of PBSC by means of DMSO 10% in an
      automated rate controlled freezer. The cells harvested from the same patient were
      divided in two equal parts and frozen according to both methods. Cryopreservation
      with HES +DMSO is better than DMSO alone in terms of viability (p<0.001) and
      Granulocyte Macrophage Colony Forming Unit (GM-CFU) activity (p<0.05). The
      freezing curves differ essentially in the slope down after the surfusion peak.
      However, surfusion peaks are similar in both conditions. The relevance of
      mechanical freezing is the saving of time and the safety of such a procedure.

PMID- 15562560
TI  - 4-methylthio 2-oxobutanoate transaminase: a specific target for antiproliferative
      agents.
AB  - We have previously shown that the addition of 4-methylthio-2-oxobutanoate (MTOB)
      to cultures of methionine dependent neoplastic cells which lack endogenous MTOB
      restores their capacity to grow in the absence of exogenous methionine.
      Transition state inhibitors of the MTOB transaminase,responsible for the
      transamination of MTOB to methionine, had also been designed and selected for
      their capacity to inhibit the proliferation of methionine dependent neoplastic
      cells but not that of normal cells in culture. We now show that the transition
      state analogue : L-methionine ethyl esterpyridoxal(MEEP) with a structure
      corresponding to the oxo acid receptor covalently linked to pyridoxamine and the
      amine donor analogue: D-aspartate beta hydroxamate (D-AH) are efficient
      inhibitors of MTOB transaminase. [3H] MEEP uptake into transformed HeLa cells is
      similar to that in normal MRC5 cells, yet growth inhibition is seem in the
      transformed but not in the normal cells.MEEP irreversibly inhibits the activity
      of this enzyme when added to HeLa cells in culture but not that of the purified
      rat liver enzyme, probably due to pyridoxal phosphate already bound in the active
      site. On the contrary, D-AH is a noncompetitive reversible inhibitor of the
      purified rat liver enzyme in vitro and also inhibits intracellular HeLa MTOB
      transaminase. Furthermore, in HeLa cells both inhibitors induce DNA strand breaks
      typical of apoptotic cell death. These results provide evidence that MTOB
      transaminase is a potential target for antiproliferative agents which could
      selectively affect methionine-dependent neoplastic cells. The transition state
      intermediale : MEEP as an amine acceptor analogue was found to be 20 fold more
      effective than D-AH as the amine donor analogue in inducing apoptosis.

PMID- 15562561
TI  - Stochastic modeling of the tumor volume assessment and growth patterns in
      hepatocellular carcinoma.
AB  - The growth pattern of hepatocellular carcinoma (HCC) arising from cirrhosis is
      variable and depends on the degree of differentiation and vascularization.
      Because growth is not constant in the natural history of HCC, prediction of
      subsequent growth rate based on tumor volume doubling time and correlation with
      histological and ultrasonographical characteristics at the moment of initial
      diagnosis are usually unreliable. The aim of our study was to assess the growth
      patterns of HCC with the aid of stochastic modeling. Thus, we included in our
      study 27 patients with histologically proven HCC, which had multiple (more than
      three)follow-up ultrasound studies in a six months interval. The patients did not
      receive any treatment during the observation period. HCC was visualized by
      computer aided ultrasound imaging, obtaining both the primary size quantification
      and the edge-detection enhancement. By a bi-cubic B-spline interpolation of
      points on the edges (3-D Bezier approximation) we approximated the surfaces
      shapes, and using the hit or miss Monte Carlo method we accurately estimate the
      tumor volume. Starting from the previous tumor volumes time series recorded
      during the first six months of evolution we applied both a linear, exponential
      and logarithmic smoothing to forecast the future size of the HCC tumor in the
      next six months. Our conclusion was that a dynamic forecasting model of HCC
      volumes could be very accurate for the assessment of tumor volume doubling time
      usually obtained by two discrete volume measurements of the tumor.

PMID- 15562562
TI  - Diffuse medulla oblongata and pontine gliomas in childhood. A review of 37 cases.
AB  - From 1975 to 1997, thirty seven newly diagnosed children aged 2 mos. to 14.3
      years with diffuse medulla oblongata or pontine tumours were referred to the
      Centre Leon Berard. Surgical biopsies were performed in 9 patients. All but one
      received radiation therapy. The mean dose of radiation was 53 Gy. Thirty two
      received chemotherapy. All patients died, one from related toxicity, and the rest
      from progressive disease. Relapses always occurred in the radiotherapy field.
      Medulla oblongata and pontine tumours would appear to have the worst outcome of
      all brain stem gliomas and should be separately analysed.

PMID- 15562563
TI  - Homophilic anchorage of brain-hexokinase to mitochondria-porins revealed by
      specific-peptide antibody cross recognition.
AB  - In brain tumors the main source of energy is from glycolysis, which is initiated
      by hexokinase 1 (HK1), an enzyme bound to the mitochondrial porin. Disruption of
      HK binding greatly affects tumor cell survival. Little is known about the
      acceptor site of HK1. Therefore, a polyclonal antibody (Pab) directed to
      MIAAQLLAYYFTELK (MK) peptide, corresponding to the 15-amino acids of the N
      terminal sequence of brain HK1 was obtained. Anti MK antibody (aMK-Pab)bound
      specifically to HK as shown by ELISA. The aMK-Pab binding to MK peptide was
      antibody-concentration dependent and was completely abolished by its
      preincubation with the peptide at 6 x 10-8 M. The aMK-Pab recognized cytosolic HK
      (cHK) and HK solubilized (sHK)from rat-brain mitochondrial preparations, but not
      the yeast HK which does not have the MK sequence. An anti-brain HK Pab (aHK-Pab)
      directed to purified HK recognized the MK peptide; aHK-Pab bound to MK and this
      binding was inhibited by preincubation of the antibody with the MK peptide. It
      was previously demonstrated that brain HK anchors to mitochondria porins, also
      designated as voltage dependent-anion channels (VDAC) via the MK sequence. A
      specific anti-VDAC antibody (aVDAC-Pab) which specifically bound the N and C
      terminal sequences of VDACwas found to bind to c-HK, sHK and MK-coated wells and
      this binding was abolished by aVDACPabpreincubation with MK peptide. These data
      suggest that the three Pabs cross-react with an epitope present in HK and VDAC,
      and which was presented in the MK peptide. Comparison of alignment of HK or VDAC
      sequences, available in the protein data bank (PDB), did not allow putative
      homologues responsible for the cross-reaction to be identified, suggesting that
      the epitope is conformational. This, added to inhibition of mitochondria-isolated
      HK binding by the MK peptide,suggests that there is an homophilic-type
      interaction between HK and porin, through a peptidic structure represented at
      least in part in the MK peptide.

PMID- 15562564
TI  - Does the primary Lung Cancer rate increase among females?
AB  - Lung cancer is still the most frequently seen malignancy among males where as
      females are less affected. Recently the lung cancer prevalence has been reported
      to increase among females in parallel to the increment in cigarette consumption.
      In our 2 clinic 11.2% (44 cases) of 393 primary lung cancer cases between 1993
      1997 were female. We evaluated the demographical characteristics and yearly
      distribution of our female patients. Mean age was 64+/-12.1 and 18.2% of the
      patients were smokers. The main complaints were dyspnoea (59%), chest pain (57%),
      fatigue (47%), cough (45%)and sputum production (32%). The cell type distribution
      rates were as follows;adenocarcinoma 45.4%, squamous cell cancer 29.5%, small
      cell cancer 20.5% and large cell cancer 4.6%. The diagnostic methods used were
      sputum cytology (27.3%),transbronchial biopsy and lavage (38.6%), thoracocentesis
      and pleural biopsy (15.8%),transthoracic fine needle aspiration (13,6%) and open
      lung biopsy (4.7%). As a result,we found a low percentage of smokers but a high
      rate of adenocarcinomas among our female patients.

PMID- 15562565
TI  - Comparison between hospitalized and screening controls in studies assessing
      breast cancer risk.
AB  - BACKGROUND: In case-control studies, selection of an appropriate group of
      controls is a critical step which may affect the outcome of the analysis.
      METHODS: We studied the differences in reproductive, lifestyle, and
      anthropometric variables between controls from a hospital-based study and
      controls from a screening clinic. Odds ratios for breast cancer were calculated
      using the two types of controls, and the impact on the resulting odds ratio was
      studied. RESULTS: Some interesting differences in odds ratios obtained with the
      two sets of controls were found. Among premenopausal screening subjects, the odds
      ratio for breast cancer did not change across quartiles of body mass,while among
      hospital subjects, the risk of breast cancer significantly decreased with
      increasing body mass. For liquor and beer consumption, a three-fold increase in
      breast cancer risk was observed among premenopausal hospital subjects, whereas no
      association was found among screening subjects. Among postmenopausal women, a
      significant decrease in breast cancer risk with ovariectomy was only observed in
      the hospital-based study. CONCLUSIONS: Our results suggest that in examining the
      association between body mass, alcohol consumption, or ovariectomy and breast
      cancer risk, the choice of control group used should be carefully considered.

PMID- 15562566
TI  - [Study of prevention and health education of obesity in China].

PMID- 15562567
TI  - Selection of patients for liver transplantation in 1997 and beyond.
AB  - Liver transplantation is now accepted as the standard surgical-medical treatment
      for end-stage liver disease, as well as replacement therapy for certain inborn
      errors of metabolism. While improvements in surgical methods and new
      immunosuppressive agents have improved survival, there remains a chronic shortage
      of available donor organs. This article offers guidelines for the physician,
      discussing indications for liver transplantation, controversial selection issues,
      contraindications, and finally, the future of liver transplantation.

PMID- 15562568
TI  - The role of prognostic models in the timing of liver transplantation. Application
      in cholestatic liver diseases.
AB  - Prognostic models have been developed for patients with primary biliary cirrhosis
      and primary sclerosing cholangitis to predict survival without transplantation.
      In patients undergoing liver transplantation, these models have been used in
      assessing postoperative mortality and morbidity. Recent data suggest that
      preoperative recipient physiology, such as impaired functional status or renal
      insufficiency, is the most important determinant of transplant outcome. Survival,
      quality of life, morbidities and resource use are the key variables to be
      considered in the timing of transplantation.

PMID- 15562569
TI  - Allocation of livers for liver transplantation: ethics and politics.
AB  - The supply of livers for transplantation is not adequate for the number of
      patients waiting for liver transplantation. The allocation and distribution of
      the limited supply of livers is hotly debated at the United Network for Organ
      Sharing. The principles of medical utility and justice must be balanced in an
      equitable distribution scheme. Excellent local liver transplant centers should be
      available to all patients.

PMID- 15562570
TI  - Contracting for services: liver transplantation in the era of mismanaged care.
AB  - It is no secret that the health care environment today is motivated by the
      underlying, largely economic impetus of managed care. This is particularly
      evident within the organ transplantation community, where third party payers hope
      to minimize their financial risk by relying more and more on "centers of
      excellence" networks to provide high-quality transplant services in an
      economically efficient manner. The burgeoning interest in the economics of liver
      transplantation raises a number of complex, yet important, issues to which
      transplant professionals should lend serious thought. This article addresses
      these issues by offering an elementary guide to contract negotiations with third
      party payers. Among other things, the article: (1) discusses several methods by
      which third party payers avert and shift risk to transplant programs; (2)
      emphasizes the importance and identifies the limitations of actuaries and other
      consulting; (3) demonstrates, with examples, how comparative analyses of existing
      data sources, both public and proprietary, can assist rational decision-making.

PMID- 15562571
TI  - Liver transplantation for alcoholic liver disease: selection and outcome.
AB  - There is clear consensus that patients with alcoholic cirrhosis should be
      considerated for liver transplantation, barring complicating medical or
      psychosocial problems. Short-term and long-term survival rates are comparable to
      patients receiving transplants for other conditions, and the relapse rate to
      alcohol use averages 15%, with troublesome drinking seen uncommonly. To date, no
      nationally accepted selection criteria have been established and proved effective
      in predicting long-term sobriety and compliance. To maximize the outcome of liver
      transplantation in patients with alcoholic liver disease, an approach to the
      selection of candidates is outlined herewith. 1. Minimum pretransplant sobriety
      period of 6 months. 2. Assessment of overall psychosocial support and stress. 3.
      Assessment of comorbid psychiatric conditions that may impair ability to comply
      with the transplant protocol during and after transplantation. 4. Assessment of
      past and present compliance with medical treatment. 5. Acceptance of problem with
      alcohol and willingness to sign an alcohol contract. 6. Willingness to
      participate in alcohol rehabilitation treatment program. 7. Willingness to
      participate in liver support groups to improve understanding of the condition and
      obtain social support. 8. Willingness to undergo random toxicology screening to
      assess compliance with sobriety.

PMID- 15562572
TI  - Prophylaxis and treatment strategies for chronic viral hepatitis in liver
      transplant patients.
AB  - This article highlights the importance of hepatotropic viruses as pathogens in
      patients undergoing liver transplantation, their contribution to morbidity and
      mortality after transplantation, and the approach to treatment of these pathogens
      when they cause disease. Although many advances have been made in the management
      of viral hepatitis in the transplant setting, there remain unanswered questions
      about the long-term natural history of the disease. An understanding of the
      pathogenesis of infection in the setting of transplantation is emerging slowly
      but requires further investigation. New approaches to treating disease in
      patients with either HBV or HCV infection are under development and will likely
      focus on the use of combinations of antiviral and immunomodulatory agents.

PMID- 15562573
TI  - Liver transplantation for hemochromatosis, Wilson's disease, and other metabolic
      disorders.
AB  - Liver transplantation provides an effective means for replacing a failing liver,
      in addition to correcting the underlying abnormality in many metabolic disorders.
      Results of liver transplantation for metabolic diseases have been generally
      encouraging, with the exception of hereditary hemochromatosis, in which
      infectious and cardiac complications appear to increase post-transplant
      mortality. Better pretransplant diagnosis of hemochromatosis, utilizing the
      recently identified putative gene, may help reduce post-transplant complications.
      In metabolic diseases, improved understanding of the underlying genetic and
      molecular defects will lead to advances in medical therapy and perhaps a
      decreased need for liver transplantation. NTBC therapy for hereditary tyrosinemia
      and purified glucocerebroside therapy for Gaucher disease are two such examples.
      The prospects of gene therapy are being actively pursued for many metabolic
      diseases, such as CF, hemophilia, and familial hypercholesterolemia. Until such
      investigation leads directly to clinical practice, however, liver transplantation
      remains an effective option for therapy for a wide range of metabolic diseases.

PMID- 15562574
TI  - Current and future treatment modalities for hepatocellular carcinoma.
AB  - This article reviews recent innovations in the treatment of Hepatocellular
      carcinoma (HCC), which, although a common malignancy, has often proved difficult
      to diagnose and treat effectively. The epidemiology and natural history of HCC
      are discussed, as well as treatments such as hepatic resection, liver
      transplantation, and cryosurgery, among others.

PMID- 15562575
TI  - Current status and outcome of pediatric liver transplantation.
AB  - In this article the diagnostic indications for hepatic transplantation are
      addressed in detail. The outcome of liver transplantation is also examined,
      including the impact of the following factors on survival: age and weight at
      transplantation, type of liver disease, and size of liver allograft, including
      living related transplantation. Morbidity and quality of life after
      transplantation are other aspects reviewed in this chapter.

PMID- 15562576
TI  - Cyclosporine and tacrolimus: the mainstay of immunosuppressive therapy for solid
      organ transplantation.
AB  - Orthotopic liver transplant is the only cure for end stage liver disease.
      Enormous progress has been made in the fields of graft and patient survival since
      the introduction of cyclosporine and tacrolimus. Scientists involved in basic and
      clinical research have dedicated their efforts to understanding the mechanisms of
      action and the side effects of these medications with the goal of finding the
      perfect balance between the well-being of the patient and the avoidance of
      rejection. A great deal of work has been done and now we can propose a variety of
      treatments suitable to different clinical scenarios. The introduction of new
      medications will offer even more options for the treatment of rejection in liver
      transplant patients.

PMID- 15562577
TI  - Cytomegalovirus infection in the liver transplant recipient. Epidemiology,
      pathogenesis, and clinical management.
AB  - The effects of cytomegalovirus (CMV) on the liver transplant patient can be
      divided into two general categories: the direct infectious disease effects (e.g.
      CMV mononucleosis, hepatitis, pneumonitis, GI infection) and the indirect effects
      that are mediated by cytokines elaborated as a consequence of the infection.
      These indirect effects include an immunosuppressive effect that contributes to
      the development of superinfection with fungi, bacteria, and Pneumocystis carinii;
      a role in the pathogenesis of allograft injury; and a role in the development of
      post-transplant lymphoproliferative disease. The two key steps in the
      pathogenesis of CMV infection-reactivation of the virus from latency and systemic
      spread-are modulated by the immunosuppressive therapy administered. New antiviral
      programs, primarily those involving ganciclovir, have resulted in considerable
      progress in the prevention and treatment of CMV disease among liver transplant
      recipients.

PMID- 15562578
TI  - Epstein-Barr virus lymphoproliferative disorders after liver transplantation.
AB  - Post-transplant lymphoproliferative disorders (PTLD) represent a spectrum of
      histological and immunological abnormalities, ranging from benign polyclonal B
      cell hyperplasia to monoclonal malignant lymphoma. The important role of Epstein
      Barr virus (EBV) in PTLD in liver transplant patients, particularly in pediatric
      recipients, is reviewed. Understanding the risks of EBV infection, the clinical
      presentations and diagnosis of PTLD, and its pathophysiology are crucial to the
      management of these disorders. Current treatment methods have resulted in better
      outcomes of these disorders, which in the past were uniformly fatal.

PMID- 15562579
TI  - Reproductive function after liver transplantation.
AB  - Successful pregnancy outcomes are possible after liver transplantation. Although
      there are risks to the mother and fetus, there has not been an increased
      incidence of malformations noted in the newborn of liver recipients. Close,
      coordinated care involving the hepatologist, surgeon, and high-risk obstetrician
      is essential to ensure a favorable outcome. Immunosuppression peripartum should
      be maintained at appropriate levels. Of note, a small subset of recipients may
      suffer worsened graft function during pregnancy. Recurrent liver disease,
      especially viral hepatitis, and CMV infection appear to pose significant risks to
      mother and offspring, respectively, although the magnitude of the risks is
      unknown. It therefore would seem prudent to consider pregnancy only in female
      liver recipients who have passed at least 1 year with stable graft function. In
      addition, new immunosuppressive regimens further add to the lack of information
      regarding pregnancy safety. The NTPR is an ongoing database to collect
      information and pregnancy outcomes. That information should be helpful in
      counseling recipients and in pregnancy management.

PMID- 15562580
TI  - Orthodontics and its discontents.

PMID- 15562581
TI  - Effects of maxillary distraction osteogenesis on the upper-airway size and nasal
      resistance in subjects with cleft lip and palate.
AB  - OBJECTIVES: To investigate the short- and long-term effects of maxillary
      distraction osteogenesis (DOG) on the upper-airway size and nasal resistance in
      nine patients with cleft lip and palate (CLP). STUDY DESIGN: Changes in the upper
      airway size were measured by using lateral cephalometric radiographs taken
      immediately before and after DOG, and 1 year later. Nasal resistance was measured
      with a rhinomanometer. An analysis of variance was used to establish statistical
      significance. Spearman correlation coefficient was used to evaluate the
      relationship between changes in the cross-sectional area of the upper airway and
      nasal resistance in association with DOG. RESULTS: Immediately after DOG, the
      anteroposterior dimension of the superior part of the upper airway was
      significantly increased (p < 0.01) and nasal resistance was significantly
      decreased (p < 0.05). Moreover, the cross-sectional area of the total upper
      airway was significantly increased (p < 0.01). There was a significant
      correlation between the increase in the upper-airway cross-sectional area and the
      reduction in nasal resistance (p < 0.05). The upper-airway size was significantly
      augmented (p < 0.05) and nasal resistance was significantly reduced (p < 0.05) at
      1 year after DOG compared with immediately before DOG. CONCLUSION: An increase in
      the upper-airway size and a reduction in nasal resistance occurred after
      maxillary DOG in patients with CLP, and these changes were stable after 1 year.

PMID- 15562582
TI  - The feasibility of measuring three-dimensional facial morphology in children.
AB  - OBJECTIVE: An investigation to determine the feasibility of measuring soft tissue
      morphology in children using a three-dimensional laser-scanning device. DESIGN:
      Prospective clinical trial. SETTING AND SAMPLE POPULATION: University of Wales,
      College of Medicine and one secondary school in the South Wales region. Sixty
      live subjects (30 adults, 30 children) were recruited in the study. EXPERIMENTAL
      VARIABLES: Laser scanned images of the subjects were obtained under a
      reproducible and controlled environment with two Minolta Vivid 900 (Osaka, Japan)
      optical laser-scanning devices assembled as a stereo-pair. A set of left and
      right scanned images was taken for each subject and each scan took an average of
      2.5 s. These scanned images were processed and merged to form a composite three
      dimensional soft tissue reproduction of the subjects using commercially available
      reverse modelling software. OUTCOME MEASURE: The shell deviations between left
      and right scan of each patient were recorded and analysed for differences. These
      differences determined whether the subjects could remain still during the time of
      the scans. RESULTS: The results showed that the mean differences between shell
      deviations for the adult scans and children scans were 0.25 +/- 0.09 and 0.30 +/-
      0.09 mm, respectively. Paired t-tests showed that the mean error between subject
      groups was 0.05 +/- 0.15 mm indicating that there was no difference between the
      two subject groups (p = 0.18). CONCLUSION: The technique as described is
      clinically reproducible for children and adults and can be used for studies
      assessing facial changes due to growth or clinical intervention.

PMID- 15562583
TI  - The efficacy of a fluoride varnish in reducing enamel demineralization adjacent
      to orthodontic brackets: an in vitro study.
AB  - OBJECTIVES: To test the hypothesis that fluoride varnish is effective in reducing
      demineralization (white spot) lesions adjacent to bonded orthodontic brackets.
      DESIGN: Two similar samples of extracted bovine incisors, with bonded orthodontic
      brackets, were separated into an experimental group (fluoride varnish was
      applied) and control group (no fluoride varnish) to examine the preventive
      effects of fluoride varnish. SETTING AND SAMPLE POPULATION: The dental clinic of
      the State University of Maringa--UEM (Maringa, Parana, Brazil). Thirty-eight
      extracted bovine incisors with bonded orthodontic brackets. EXPERIMENTAL
      VARIABLE: Fluoride varnish was applied topically to half of the sample of
      extracted bovine teeth. No varnish was applied to the other half. OUTCOME
      MEASURE: The depths of enamel demineralization (white spot) lesions were measured
      from polarized light microscopy images using image analysis software. RESULTS:
      The teeth in both the experimental and control groups had been exposed to a
      cariogenic environment twice a day for 35 days. Those teeth that had been treated
      with two applications of fluoride varnish (one at the outset and another 15 days
      later) demonstrated about 38% less mean lesion depth than teeth where no varnish
      had been applied. CONCLUSION: Orthodontists may wish to consider the application
      of fluoride varnish during fixed orthodontic therapy to help reduce the
      development of enamel white spot lesions.

PMID- 15562584
TI  - The influence of jaw innervation on the dental maturation pattern in the
      mandible.
AB  - OBJECTIVES: To explore the relationship between mandibular dental maturation and
      the pattern of jaw innervation. SETTING AND SAMPLE POPULATION: The sample
      included 365 panoramic radiographs taken in the period 1965-1969 in a Danish
      municipality. DESIGN: For assessing dental maturity, the seven left mandibular
      teeth (M2, M1, P2, P1, C, I2, I1) were given a dental maturity score according to
      a method introduced by Demirjian. Spearman correlation coefficients between the
      maturity score of an index tooth (one of each teeth) and the maturity score of
      the 6 other teeth was calculated and illustrated. RESULTS: All the correlation
      coefficients were larger than 0.5 indicating a rather high level of association
      between the development of mandibular teeth in the same individual. Thus,
      associations between the pattern of dental maturation and jaw innervation were
      not obvious. CONCLUSION: When the correlation between the dental maturity stages
      was analysed, no significant relation was found between dental maturation and jaw
      innervation in the mandible. This is interesting considering the results
      presented in a recent study, which showed that the clinical observed tooth
      eruption was closely related to the pattern of jaw innervation. Those authors
      suggested that the factors influencing the eruption might be associated with jaw
      innervation. In our study, the stepwise dental maturation process, however, is
      not equally associated with jaw innervation.

PMID- 15562585
TI  - Abnormal craniofacial development and expression patterns of extracellular matrix
      components in transgenic Del1 mice harboring a deletion mutation in the type II
      collagen gene.
AB  - OBJECTIVE: To analyze the effect of a type II collagen mutation on craniofacial
      development in transgenic Del1 mice. DESIGN: Samples from homozygous (+/+) and
      heterozygous (+/-) transgenic Del1 mice harboring mutations in the type II
      collagen gene as well as non-transgenic (-/-) littermates were collected at days
      12.5, 14.5, 16.5 and 18.5 of gestation. The cartilaginous and bony elements of
      the craniofacial skeleton were analyzed after staining with alcian blue, alizarin
      red S and von Kossa. The expression patterns of type II, IX and X collagens and
      aggrecan were analyzed by immunohistochemistry and in situ hybridization.
      RESULTS: Several abnormalities were observed in the craniofacial skeleton of
      transgenic Del1 mice. These include an overall retardation of chondrogenesis and
      osteogenesis in Del1 +/+ mice, and to a lesser extent also in Del1+/- mice.
      Characteristic findings in Del1 +/+ mice included a reduced anterioposterior
      length, a smaller size of the mandible, a palatal cleft and a downward bending
      snout. We also detected retarded ossification of calvarial bones in Del1 +/+ and
      +/- mice when compared with Del1 -/- mice. A surprising finding was the presence
      of both type II and X collagens and their mRNAs in the periosteum of the cranial
      base. CONCLUSION: The present study confirms the important role of type II
      collagen mutation in craniofacial development and growth. In addition to
      affecting endochondral ossification, the type II collagen mutation also disturbs
      intramembranous ossification in the developing craniofacial skeleton.

PMID- 15562586
TI  - Inhibition of human embryonic palatal mesenchymal cell cycle by secalonic acid D:
      a probable mechanism of its cleft palate induction.
AB  - OBJECTIVE: To assess the mechanism(s) of cleft palate induction by secalonic acid
      D (SAD) in human embryonic palatal mesenchymal (HEPM) cells and compare them with
      those evaluated in the murine embryonic palate. DESIGN: Effect of SAD on HEPM
      cell proliferation was studied by obtaining dose response curves for cell
      numbers, uptake of 3H-thymidine and the expression of proliferating cell nuclear
      antigen (PCNA). Effects of SAD on cell cycle were assessed by flowcytometry. Cell
      labeling with 3H-glucosamine and immunoblot analysis were conducted to study SAD
      effects on the synthesis of glycosaminogycans (GAG) and the expression of
      fibronectin and tenascin, respectively. RESULTS: SAD induced a concentration
      dependent decrease in HEPM cell number and 3H-thymidine uptake beginning at 0.1
      microg of SAD/ml. Expression of PCNA and progression of cell cycle from G1 to S
      phase were inhibited following SAD exposure. Cell viability was significantly
      reduced only at 7.5 microg/ml of SAD or higher indicating that the reduction in
      cell numbers by SAD at lower concentrations is likely due to reduced
      proliferation and at higher concentrations due to both reduced proliferation and
      cell death. Synthesis of extra cellular matrix components (GAGs, fibronectin or
      tenascin) by HEPM cells, however, was not inhibited by SAD. CONCLUSION: The
      results of these studies confirmed those of our previous studies with mice and
      the MEPM cells that SAD may induce cleft palate by reducing numbers of palatal
      mesenchymal cells by inhibition of their proliferation thereby leading to a
      reduction in the size of the developing palate shelves.

PMID- 15562587
TI  - Prevalence of temporomandibular joint dysfunction in Ehlers-Danlos syndromes.

PMID- 15562588
TI  - The myxozoan fauna of spottail shiner in the Great Lakes basin: membership,
      richness, and geographical distribution.
AB  - Spottail shiner (Notropis hudsonius) from localities in each of the Great Lakes
      plus some nearby waterbodies, i.e., the St. Lawrence River, and the Chester
      River, Maryland, were examined for myxozoan parasites. A total of 10 species was
      found, including 7 histozoic (Myxobolus sp.; M. algonquinensis Xiao and Desser,
      1997; M. bartai Salim and Desser, 2000; M. xiaoi Salim and Desser, 2000; M.
      fanthami Landsberg and Lom, 1991; M. hendricksoni Mitchell, Seymour, and Gamble,
      1985; Thelohanellus notatus Mavor, 1916) and 3 coelozoic (Chloromyxum sp.,
      Zschokkella sp., Sphaerospora sp.) representatives. Infracommunity richness
      varied from 0 to 5 species per fish; mean infracommunity richness varied from 0
      to 2.5 species. Component community richness varied from 0 to 7. Significant
      positive correlations were observed between mean and maximum infracommunity
      richness and component community richness. Similarly, maximum prevalence of each
      species at any 1 site was positively correlated with geographic range as measured
      by number of localities where a parasite species was encountered. Individual
      species occurred independently of each other. Representative histozoic and
      coelozoic species displayed similarly widespread distributions from Wisconsin to
      Maryland, but overall, histozoic species were dominant members within component
      communities. The study concludes that, under the present taxonomic paradigm,
      species parasitizing spottail shiner appear to be part of a larger network that
      cycles, in varying degrees, through certain other cyprinid and catostomid fish.
      The challenge of future research is to determine whether each parasite species
      constitutes single or multiple genetically isolated populations.

PMID- 15562589
TI  - Population structure of Anisakis simplex (Nematoda) in harbor porpoises Phocoena
      phocoena off Denmark.
AB  - The population structure and habitat selection of Anisakis simplex in 35 harbor
      porpoises off Denmark are described. The nematodes were collected from the
      stomach and duodenal ampulla and were categorized as third-stage larvae, fourth
      stage larvae, subadults, and adults. The porpoises harbored 8,043 specimens of A.
      simplex. The proportion of adults and subadults increased with infrapopulation
      size. The number of development stages across infrapopulations covaried
      significantly (Kendall's test of concordance). Concordance was higher in hosts
      with the highest intensities than in those with low and medium intensities. All
      stages occurred mainly in the forestomach, but this trend was stronger for the
      adults. Adult and subadult sex ratios did not depart significantly from 1:1. Our
      data suggested that recruitment and duration of each stage were the main factors
      accounting for infrapopulation structure. The preference of A. simplex for the
      forestomach conformed with previous studies, but the narrower distribution of
      adults relative to other stages might indicate a strategy to enhance mating
      opportunities. Information on sex ratios of A. simplex is scarce and
      contradictory. We suggest that the discrepancies might partly reflect differences
      in categorization criteria and statistical methods.

PMID- 15562590
TI  - Effects of host sociality on ectoparasite population biology.
AB  - Theory predicts a positive relationship between parasite infection intensity and
      host density. However, this generalization is complicated in natural systems by
      differences in life history among parasite taxa, e.g., transmissibility.
      Accordingly, predictions relating host density to parasite load should be
      specific to each parasite taxon. To illustrate this, we studied parasites that
      differed greatly in life history in the context of the Galapagos hawk's (Buteo
      galapagoensis) variably cooperative mating system. Two louse (Phthiraptera)
      species were collected: Colpocephalum turbinatum (Amblycera), with 53 host
      species, and Degeeriella regalis (Ischnocera), with 10 host species, although B.
      galapagoensis was the only known Galapagos host. Sixty territorial adult male
      hawks from 26 groups of 1-6 males were quantitatively sampled for lice. Average
      abundance and intensity of C. turbinatum but not D. regalis were significantly
      larger in large groups of hawks than small groups. Males from the same
      polyandrous group harbored significantly correlated abundances of C. turbinatum
      but not D. regalis. Prevalence, average abundance, and intensity of C. turbinatum
      were significantly higher than D. regalis. These are the first results to
      demonstrate significant differences in a suite of population responses between
      these louse suborders in the context of host sociality.

PMID- 15562591
TI  - Aspects of the ecology and natural history of Paraergasilus rylovi (Copepoda,
      Ergasilidae) parasitic in unionids of Finland.
AB  - The distribution of Paraergasilus rylovi in 17 populations of unionids was
      investigated. In 1 unionid population, the parasite was studied regarding host
      age, size, sex, and the reproductive period (occurrence of egg sacs). Results
      from pooled material from the years 1987--1989 and 1996 (southern Finland, 11
      populations) indicated that Anodonta piscinalis (n = 1,359) is the main host
      (total mean prevalence 71% and intensity +/-SE of infection 16.4+/-0.6).
      Pseudanodonta complanata (n = 106) was infected occasionally (3% and 1.3+/-0.3),
      whereas Unio pictorum (n = 108) and U. tumidus (n = 17) were not infected.
      Results from 17 A. piscinalis populations showed that P. rylovi occurs in
      southern Finland but not in northern Finland. In A. piscinalis, the mean
      intensity of infection was higher in lake populations than in river populations.
      Both host age and length had a negative relationship with the intensity of P.
      rylovi infection. Host sex did not affect the intensity of infection. Egg sacs of
      P. rylovi were found from June to August. There was a tendency for higher
      intensities of infection in autumn. Infection by the digenean Rhipidocotyle
      fennica had no effect on the intensity of P. rylovi infection.

PMID- 15562592
TI  - New Wolbachia endosymbionts from Nearctic and Neotropical fleas (Siphonaptera).
AB  - Several species of fleas (Siphonaptera), ectoparasites of mammals and birds, have
      recently been shown to harbor species of Wolbachia. Here, we extend this data set
      to 20 more species of Siphonaptera (Rhopalopsyllidae, Stephanocircidae,
      Pulicidae, Ceratophyllidae, Ctenophthalmidae, Ischnopsyllidae, Leptopsyllidae,
      and Malacopsyllidae) from sylvatic populations throughout the Nearctic and
      Neotropical regions. Using polymerase chain reaction, we targeted the Wolbachia
      16S ribosomal DNA (rDNA) gene. Applying maximum parsimony- and maximum likelihood
      based algorithms, as well as statistical parsimony, we conducted a phylogenetic
      analysis of Wolbachia 16S rDNA to evaluate its position within the known
      Wolbachia spp. The analysis recovered the siphonapteran Wolbachia 16S rDNA
      sequences as a monophyletic group and shows multiple haplotype connections
      between the Neotropical and Nearctic Wolbachia strains of fleas.

PMID- 15562593
TI  - A third species of Hypoderma (Diptera: Oestridae) affecting cattle and yaks in
      China: molecular and morphological evidence.
AB  - Cattle and yak hypodermosis in China is caused by Hypoderma bovis and H.
      lineatum, with a prevalence reaching up to 98-100% of the animals and maximum
      intensities exceeding 400 warbles for each animal. A third species, H. sinense,
      is also considered by Chinese researchers to affect livestock. The molecular
      characterization of the most variable region of the mitochondrial cytochrome
      oxidase I gene and of the ribosomal 28S gene has been performed for the third
      stage larvae collected from cattle and yaks in China and identified (on the basis
      of the spinulation on the ventral side of the 10th segment) as H. bovis, H.
      lineatum, and H. sinense. Amplicons were digested with the HinfI and BfaI
      restriction enzymes, which provided diagnostic profiles to simultaneously
      differentiate the 3 Hypoderma species. Third-stage larvae of H. sinense were also
      examined by scanning electron microscopy, which revealed proper morphological
      characteristics different from those of H. bovis and H. lineatum. The molecular
      and morphological evidence herein reported support the existence of a third
      species of Hypoderma affecting cattle and yaks in China, and the results provide
      new tools for unequivocal identification of this species and present key
      components for the evaluation of its endogenous cycle and pathogenicity in
      animals and humans.

PMID- 15562594
TI  - Duplaccessorius andinus n. gen., n. sp. (Dactylogyridae: Ancyrocephalinae) from
      the gills of Percichthys trucha (Perciformes: Percichthyidae) in Patagonia,
      Argentina.
AB  - During a parasitological survey of Patagonian freshwater fishes, specimens of a
      new species of Monogenea were collected from the gills of Percichthys trucha
      (Perciformes: Percichthyidae). This species is described as the only member of a
      newly proposed genus of Ancyrocephalinae. Duplaccessorius n. gen.
      (Dactylogyridae, Ancyrocephalinae) is characterized by hooks with 2 subunits,
      gonads in tandem, a coiled male copulatory organ with counterclockwise rings, an
      accessory piece formed by 2 distinct parts, and a nonsclerotized sinistrolateral
      vagina with a funnel shape vestibule. Duplaccessorius andinus n. sp. infects the
      gills of P. trucha (Cuvier and Valenciennes, 1840) from Andean Patagonian lakes,
      being the first species of Ancyrocephalinae described from a South American
      percichthyid.

PMID- 15562595
TI  - African trypanosome interactions with an in vitro model of the human blood-brain
      barrier.
AB  - The neurological manifestations of sleeping sickness in man are attributed to the
      penetration of the blood-brain barrier (BBB) and invasion of the central nervous
      system by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense.
      However, how African trypanosomes cross the BBB remains an unresolved issue. We
      have examined the traversal of African trypanosomes across the human BBB using an
      in vitro BBB model system constructed of human brain microvascular endothelial
      cells (BMECs) grown on Costar Transwell inserts. Human-infective T. b. gambiense
      strain IL 1852 was found to cross human BMECs far more readily than the animal
      infective Trypanosoma brucei brucei strains 427 and TREU 927. Tsetse fly
      infective procyclic trypomastigotes did not cross the human BMECs either alone or
      when coincubated with bloodstreamform T. b. gambiense. After overnight
      incubation, the integrity of the human BMEC monolayer measured by
      transendothelial electrical resistance was maintained on the inserts relative to
      the controls when the endothelial cells were incubated with T. b. brucei.
      However, decreases in electrical resistance were observed when the BMEC-coated
      inserts were incubated with T. b. gambiense. Light and electron microscopy
      studies revealed that T. b. gambiense initially bind at or near intercellular
      junctions before crossing the BBB paracellularly. This is the first demonstration
      of paracellular traversal of African trypanosomes across the BBB. Further studies
      are required to determine the mechanism of BBB traversal by these parasites at
      the cellular and molecular level.

PMID- 15562596
TI  - Microbial adhesion of Cryptosporidium parvum sporozoites: purification of an
      inhibitory lipid from bovine mucosa.
AB  - Cryptosporidium parvum is a protozoan pathogen of humans and livestock worldwide.
      Its ability to infect a wide range of species raises questions as to the
      involvement of a specific host cell receptor for parasite-host recognition. To
      investigate the mechanism of parasite-host cell recognition, we have developed an
      in vitro cell suspension binding assay to investigate adhesion of C. parvum
      sporozoites to host cells. Morphologic features of binding events observed with
      this assay were identical to those described in natural infections.
      Glycoconjugates, Madin Darby bovine kidney (MDBK) cell fractions, and plasma
      membrane vesicles (PMVs) were screened for their ability to block binding of
      sporozoites to MDBK cells. Mucins, MDBK cell fractions, and PMVs exhibited dose
      dependent inhibition of sporozoite binding. The major inhibitory fraction from
      MDBK cells was found to be insoluble in aqueous medium, nonsaponifiable, and
      lacking carbohydrate moieties, nitrogen, and phosphorus. Its inhibitory effect
      was resistant to heat, protease digestion, and glycosidase treatment, suggesting
      that the inhibitory activity is a lipid or a lipid-like component. The inhibitory
      activity was purified from MDBK cells, and in larger amounts from bovine small
      intestinal mucosa, by organic solvent extraction, semipreparative high-pressure
      liquid chromatography, and preparative high-performance thin-layer
      chromatography. Biochemical analyses, thin-layer chromatography staining
      techniques, mass spectrometry, and elemental analysis were used to partially
      characterize the purified lipid. These results indicate that a host intestinal
      lipid(s) or a lipid-like component(s) may play an important role in the early
      stages of host cell invasion by C. parvum.

PMID- 15562597
TI  - The mitochondrial genome of Biomphalaria glabrata (Gastropoda: Basommatophora),
      intermediate host of Schistosoma mansoni.
AB  - The complete mitochondrial (Mt) genome of the gastropod Biomphalaria glabrata, a
      major intermediate host for the human parasite Schistosoma mansoni, was
      sequenced. The circular genome, the first determined from a basommatophoran
      snail, is AT rich (74.6%) and the smallest Mt genome (13,670 nucleotides [nt])
      characterized from mollusks to date. Sequences from 2 B. glabrata strains, M-line
      and 1742, differed by only 18 nt. Phylogenetic analysis of 16S and ND1 sequences
      confirmed the Brazilian ancestry of both B. glabrata strains. Gene predictions
      indicated 22 transfer RNA, 12S and 16S ribosomal RNA (rRNA), and 13 protein
      encoding genes, as is typical for metazoans. Of the mollusk Mt genomes currently
      known, the gene order was most similar to that of stylommatophoran gastropods,
      concordant with the monophyly of pulmonate gastropods. Screening of GenBank
      (expressed sequence tags database [dbEST]) with the Mt sequence identified 108
      entries from B. glabrata as Mt-derived sequences, including 12S and 16S rRNA
      sequences. Moreover, 11 sequences originating from the Mt genome of B. glabrata
      were identified among EST entries ascribed to intramolluskan stages of S.
      mansoni. The availability of this Mt sequence will facilitate further molecular
      investigations into the biology of Biomphalaria sp. and interactions between this
      intermediate host and intramolluskan stages of S. mansoni.

PMID- 15562598
TI  - Evidence of p-glycoprotein sequence diversity in cyathostomins.
AB  - P-glycoproteins (Pgps) are adenosine triphosphate-binding transporter proteins
      thought to be associated with multi-drug resistance in mammals and protozoans and
      have been suggested to be involved in the mechanism of ivermectin (IVM)
      resistance in Haemonchus contortus. Until now, resistance to IVM has not been
      reported in cyathostomins in horses in spite of its widespread and frequent use.
      Reasons for this might be differences in the molecular mechanism of the
      development of resistance. Based on this hypothesis, the present study was
      carried out to find homologues of Pgp in cyathostomins. A 416-bp polymerase chain
      reaction (PCR) product was generated using complementary DNA (cDNA) of
      Cylicocyclus elongatus and Cylicocyclus insigne and degenerate primers, located
      in the conserved Pgp nucleotide-binding domains. Resulting PCR products showed
      interspecific nucleotide and amino acid sequence identities of 73.3 and 76.8%,
      respectively. Specific primers were designed based on the Cc. elongatus sequence,
      and a PCR product of 268-bp was amplified from cDNA of single adults of
      Cylicocyclus radiatus, Cc. insigne, Cylicocyclus nassatus, Cc. elongatus,
      Cylicostephanus hybridus (2 individuals), Cylicostephanus goldi, Cyathostomum
      pateratum, Cyathostomum coronatum, and Cyathostomum catinatum. Two clusters of
      sequences were found representing 2 different internucleotide-binding domains
      (IBDs). A further distinct IBD is represented by the 416-bp PCR product of Cc.
      insigne. Therefore, a total of 3 clearly different sequences of the IBD were
      cloned and sequenced, suggesting that at least 2 Pgp genes exist in
      cyathostomins.

PMID- 15562599
TI  - Gene organization and expression of the divalent cation transporter Nramp in the
      protistan parasite Perkinsus marinus.
AB  - Trophozoites of the protistan parasite Perkinsus marinus reside and proliferate
      inside phagosomelike structures of hemocytes from the host, the eastern oyster
      Crassostrea virginica. In a murine model, it has been proposed that the outcome
      of intracellular parasite-host interactions is determined, at least in part, by
      the activity of the host's divalent cation transporter natural resistance
      associated macrophage protein 1 (Nramp1). Although nucleotide sequences from
      members of the Nramp family in protozoan parasites have recently become available
      in public databases, little is known about their molecular, structural, and
      functional aspects that may relate to the parasite's survival of intracellular
      killing by the host. The complementary DNA (cDNA) sequence of the Nramp from P.
      marinus (PmNramp) was obtained by polymerase chain reaction amplification with
      degenerated primers, followed by rapid amplification of cDNA ends. The 2,082-bp
      cDNA sequence encoded a predicted protein of 558 amino acids. PmNramp is a single
      copy gene composed of 7 exons and 6 short introns (44-61 bp) with the canonical
      splicing signal (GT/AG). A phylogenetic analysis indicates that P. marinus and
      apicomplexan Nramp genes derive from a common "archetype" Nramp ancestor.
      However, the apicomplexan Nramps are highly divergent from the P. marinus
      sequence and the rest of the archetype Nramp group. Preliminary studies suggest
      that expression of PmNramp in in vitro-cultured P. marinus trophozoites is
      modulated by metals and by exogenous oxidative stress.

PMID- 15562600
TI  - Tissue distribution and molecular characterization of chicken isolates of
      Toxoplasma gondii from Peru.
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator
      of the prevalence of T. gondii oocysts in the soil because chickens feed from the
      ground. The prevalence of T. gondii antibodies in sera of 50 free-range chickens
      (Gallus domesticus) from Peru was 26% on the basis of the modified agglutination
      test (MAT). Hearts, pectoral muscles, and brains of seropositive (MAT > or =1:5)
      chickens were bioassayed individually in mice. Tissues from the remaining 37
      seronegative chickens were pooled and fed to 2 T. gondii-free cats. Feces of cats
      were examined for oocysts; they did not shed oocysts. Toxoplasma gondii was
      isolated from the hearts of 10 seropositive chickens but not from their brains
      and pectoral muscles. Genotyping of these isolates using the SAG2 locus indicated
      that 7 isolates were type I and 3 were type III. Six of the 7 type-I isolates
      were avirulent for mice, which was unusual because type-I isolates are considered
      virulent for mice. The T. gondii isolates were from chickens from different
      properties that were at least 200 m apart. Thus, each isolate is likely to be
      different. This is the first report of isolation of T. gondii from chickens from
      Peru.

PMID- 15562601
TI  - Villus epithelial injury induced by infection with the nematode Nippostrongylus
      brasiliensis is associated with upregulation of granzyme B.
AB  - Intestinal parasite infections induce thymus-dependent villus atrophy, but the
      effector mechanisms directly responsible for the development of villus atrophy
      are not thoroughly understood. In this study, we analyzed the expression of
      cytotoxic factors or ligands in athymic nude rnu/rnu rats and their littermate
      euthymic rnu/+ rats infected with the nematode Nippostrongylus brasiliensis.
      Morphometric analyses showed that partial villus atrophy developed 10 days after
      infection in euthymic but not in athymic rats, whereas crypt hyperplasia occurred
      in both types of animal. Reverse transcription-polymerase chain reaction analyses
      of the isolated jejunal epithelial fraction showed that the development of villus
      atrophy in euthymic rats was positively correlated with an increase of granzyme B
      transcript levels but not with Fas ligand or tumor necrosis factor-alpha
      expression. In addition, the number of granzyme B-immunoreactive cells was
      increased significantly in euthymic rat villus epithelium and the propria mucosa
      after infection. The CD8+ cell number did not change significantly. Collectively,
      these findings showed that significant increases in the number of cells that
      express the cytotoxic factor granzyme B occur in the nematode-infected small
      intestine of immunocompetent hosts. The type of cells that express granzyme B and
      their role in the progression of enteropathy remain to be elucidated.

PMID- 15562602
TI  - Antigenic evaluation of a recombinant baculovirus-expressed Sarcocystis neurona
      SAG1 antigen.
AB  - Sarcocystis neurona is the primary parasite associated with equine protozoal
      myeloencephalitis (EPM). This is a commonly diagnosed neurological disorder in
      the Americas that infects the central nervous system of horses. Current serologic
      assays utilize culture-derived parasites as antigen. This method requires large
      numbers of parasites to be grown in culture, which is labor intensive and time
      consuming. Also, a culture-derived whole-parasite preparation contains conserved
      antigens that could cross-react with antibodies against other Sarcocystis species
      and members of Sarcocystidae such as Neospora spp., Hammondia spp., and
      Toxoplasma gondii. Therefore, there is a need to develop an improved method for
      the detection of S. neurona-specific antibodies. The sera of infected horses
      react strongly to surface antigen 1 (SnSAG1), an approximately 29-kDa protein, in
      immunoblot analysis, suggesting that it is an immunodominant antigen. The SnSAG1
      gene of S. neurona was cloned, and recombinant S. neurona SAG1 protein (rSnSAG1
      Bac) was expressed with the use of a baculovirus system. By immunoblot analysis,
      the rSnSAG1-Bac antigen detected antibodies to S. neurona from naturally infected
      and experimentally inoculated equids, cats, rabbit, mice, and skunk. This is the
      first report of a baculovirus-expressed recombinant S. neurona antigen being used
      to detect anti-S. neurona antibodies in a variety of host species.

PMID- 15562603
TI  - Identification of transcripts generated during the response of resistant
      Biomphalaria glabrata to Schistosoma mansoni infection using suppression
      subtractive hybridization.
AB  - Suppression subtractive hybridization (SSH) was used to construct a complementary
      DNA library enriched for transcripts more abundantly expressed in the resistant
      BS90 strain of Biomphalaria glabrata at 12 hr postinfection with Schistosoma
      mansoni as compared with the susceptible M-line strain under the same
      circumstances. One hundred and twelve clones of the library were sequenced,
      yielding 88 unique SSH-expressed sequence tags (ESTs). Differential expression
      screening indicated that 22 of the 88 unique transcripts were strong candidates
      for differential expression in the BS90 strain relative to the M-line strain.
      Analysis of a subset of 4 transcripts using quantitative reverse transcriptase
      polymerase chain reaction (qPCR) substantially supports the patterns obtained
      using the differential expression screen. Furthermore, the qPCR results revealed
      that gene upregulation in resistant snails, downregulation in susceptible snails,
      and differences in constitutive gene expression can all account for differential
      expression during the defense responses of resistant and susceptible snails. The
      majority (71.6%) of the SSH-ESTs recovered consisted of novel sequences not
      identified by sequence similarity to known genes. This work complements previous
      efforts to elucidate the genetic components underlying a successful response to
      S. mansoni by B. glabrata and identifies a series of transcripts deserving
      additional study in comparing susceptible and resistant snails.

PMID- 15562604
TI  - Parasites of native and nonnative fishes of the Little Colorado River, Grand
      Canyon, Arizona.
AB  - A 2-yr, seasonal, parasitological study of 1,435 fish, belonging to 4 species of
      native fishes and 7 species of nonnative fishes from the lower Little Colorado
      River (LCR) and tributary creeks, Grand Canyon, Arizona, yielded 17 species of
      parasites. These comprised 1 myxozoan (Henneguya exilis), 2 copepods (Ergasilus
      arthrosis and Lernaea cyprinacea), 1 acarine (Oribatida gen. sp.), 1 piscicolid
      leech (Myzobdella lugubris), 4 monogeneans (Gyrodactylus hoffmani, Gyrodactylus
      sp., Dactylogyrus extensus, and Ligictaluridus floridanus), 4 nematodes
      (Contracaecum sp., Eustrongylides sp., Rhabdochona sp., and Truttaedacnitis
      truttae), 3 cestodes (Bothriocephalus acheilognathi, Corallobothrium fimbriatum,
      and Megathylacoides giganteum), and 2 trematodes (Ornithodiplostomum sp. and
      Posthodiplostomum sp.). Rhabdochona sp. was the only adult parasite native to the
      LCR. Infection intensities of Ornithodiplostomum sp. and B. acheilognathi were
      positively correlated with length of the humpback chub Gila cypha. Adult
      helminths showed a high degree of host specificity, except B. acheilognathi,
      which was recovered from all fish species examined but was most abundant in
      cyprinids. Abundance of B. acheilognathi in the humpback chub was highest in the
      fall and lowest in the summer in both reaches of the LCR. There was no major
      taxonomic difference in parasite assemblages between the 2 different reaches of
      the river (LC1 and LC2). Parasite community diversity was very similar in
      humpback chub, regardless of sampling site or time. The parasite fauna of the LCR
      is numerically dominated by B. acheilognathi and metacercariae of
      Ornithodiplostomum sp. The richest and most diverse component community occurred
      in a nonnative species, the channel catfish Ictalurus punctatus, but
      infracommunity species richness was highest in a native host, humpback chub.

PMID- 15562605
TI  - Survival of Toxoplasma gondii oocysts in Eastern oysters (Crassostrea virginica).
AB  - Toxoplasma gondii has recently been recognized to be widely prevalent in the
      marine environment. It has previously been determined that Eastern oysters
      (Crassostrea virginica) can remove sporulated T. gondii oocysts from seawater and
      that oocysts retain their infectivity for mice. This study examined the long-term
      survival of T. gondii oocysts in oysters and examined how efficient oysters were
      at removing oocysts from seawater. Oysters in 76-L aquaria (15 oysters per
      aquarium) were exposed to 1 x 10(6) oocysts for 24 hr and examined at intervals
      up to 85 days postexposure (PE). Ninety percent (9 of 10) of these oysters were
      positive on day 1 PE using mouse bioassay. Tissue cysts were observed in 1 of 2
      mice fed tissue from oysters exposed 21 days previously. Toxoplasma gondii
      antibodies were found in 2 of 3 mice fed oysters that had been exposed 85 days
      previously. In another study, groups of 10 oysters in 76-L aquaria were exposed
      to 1 x 10(5), 5 x 10(4), or 1 x 10(4) sporulated T. gondii oocysts for 24 hr and
      then processed for bioassay in mice. All oysters exposed to 1 x 10(5) oocysts
      were infected, and 60% of oysters exposed to 5 x 10(4) oocysts were positive when
      fed to mice. The studies with exposure to 1 x 10(4) oocysts were repeated twice,
      and 10 and 25% of oysters were positive when fed to mice. These studies indicate
      that T. gondii can survive for several months in oysters and that oysters can
      readily remove T. gondii oocysts from seawater. Infected filter feeders may serve
      as a source of T. gondii for marine mammals and possibly humans.

PMID- 15562606
TI  - Helminth communities of the lesser sandeel Ammodytes tobianus L. off the west
      coast of Ireland.
AB  - The helminth parasites present in 412 lesser sandeels (Ammodytes tobianus) taken
      from June 1996 to May 1997 from the Aran Islands on the west coast of Ireland
      were examined. Ten helminth parasite species were recorded, and more than 92% of
      the sandeels were infected with at least 1 helminth species. Seven of the species
      were digeneans, including Brachyphallus crenatus, Hemiurus communis, Derogenes
      varicus, Lecithaster gibbosus, Opechona bacillaris, Cryptocotyle lingua, and
      Galactosomum lacteum; 2 nematodes, including Hysterothylacium sp. and
      Contracaecum sp.; and 1 cestode, Scolex pleuronectis. Three of the 7 digenean
      species were either larvae or immature. Only 2 species, the digeneans G. lacteum
      and H. communis, had prevalences greater than 50%. The dominant species was G.
      lacteum, accounting for 67% of all parasites present. The relationship between
      spawned groups, host length, and season versus the abundance, prevalence, species
      richness, and the total number of parasites in the infracommunities was
      investigated. No difference was found between the parasite communities of the 2
      spawning races of the host population. Mean abundance and prevalence of the
      different parasite species showed seasonal variation. Numbers of parasite species
      and numbers of parasites increased with fish length. The role of A. tobianus as
      an intermediate host for helminths was assessed; it was determined that most were
      infectious to birds or mammals, with the majority of the parasite species being
      autogenic (infectious to fish). The mean number of parasites per fish was nearly
      a quarter of the value recorded for A. tobianus in the North Sea, where a much
      higher intensity of infection was recorded.

PMID- 15562607
TI  - Functional characterization of an LCCL-lectin domain containing protein family in
      Plasmodium berghei.
AB  - Using bioinformatic, proteomic, immunofluorescence, and genetic cross methods, we
      have functionally characterized a family of putative parasite ligands as
      potential mediators of cell-cell interactions. We name these proteins the Limulus
      clotting factor C, Coch-5b2, and Lgl1 (LCCL)-lectin adhesive-like protein (LAP)
      family. We demonstrate that this family is conserved amongst Plasmodium spp. It
      possesses a unique arrangement of adhesive protein domains normally associated
      with extracellular proteins. The proteins are expressed predominantly, though not
      exclusively, in the mosquito stages of the life cycle. We test the hypothesis
      that these proteins are surface proteins with 1 member of this gene family, lap1,
      and provide evidence that it is expressed on the surface of Plasmodium berghei
      sporozoites. Finally, through genetic crosses of wild-type Pblap1+ and transgenic
      Pblap1- parasites, we show that the null phenotype previously reported for
      sporozoite development in a Pblap1- mutant can be rescued within a heterokaryotic
      oocyst and that infectious Pblap1 sporozoites can be formed. The mutant is not
      rescued by coparasitization of mosquitoes with a mixture Pblap1+ and Pblap1-
      homokaryotic oocysts.

PMID- 15562608
TI  - New species of Cinclotaenia macy, 1973 (Cyclophyllidea: Dilepididae) from Cinclus
      leucocephalus tschudi (Passeriformes: Cinclidae) in Bolivia.
AB  - Two new species of Cinclotaenia (Cyclophyllidea: Dilepididae) are described from
      the small intestine of Cinclus leucocephalus (Aves: Passeriformes: Cinclidae)
      collected in the Yungas region of Bolivia. Cinclotaenia minuta n. sp. is
      characterized by possessing a minute strobila with a maximum body length of 1.58
      mm, consisting of 5-10 proglottids, 19-22 rostellar hooks with lengths from 16 to
      17 microm, 12-17 testes per proglottid, and eggs forming packets without
      filaments. Cinclotaenia boliviensis n. sp. has bandlike strobila with a length up
      to 26 mm with 67-74 proglittids, 22 rostellar hooks with length 39-42 microm, 43
      68 testes, and eggs forming packets possessing long filaments. The systematic
      position in Cinclotaenia of cestodes lacking filaments on the egg packets is
      confirmed. This is the first record of species of Cinclotaenia in dippers from
      Bolivia and also the first report of cestodes from Cinclus sp. in the Neotropical
      Region.

PMID- 15562609
TI  - Phylogeny for species of Haemonchus (Nematoda: Trichostrongyloidea):
      considerations of their evolutionary history and global biogeography among
      Camelidae and Pecora (Artiodactyla).
AB  - Phylogenetic analysis of 25 morphological characters among the 12 species of
      Haemonchus resulted in 1 most parsimonious tree (60 steps; consistency index =
      0.67, retention index = 0.80). Monophyly for Haemonchus was diagnosed by 3
      unequivocal synapomorphies, including the asymmetric origin of the dorsal ray,
      relative size of the ventral rays, and the presence of a barb on each spicule
      tip. Species of Haemonchus have complex histories with respect to host and
      geographic associations: (1) origins in Africa with basal diversification in
      antelopes (H. krugeri, H. lawrencei, H. dinniki, H. horaki), (2) independent
      events of colonization for those species in Caprini and Bovinae (H. contortus, H.
      placei, H. bedfordi, H. similis), (3) colonization and development of core host
      associations within Camelidae (H. longistipes) and among Antilopinae,
      Tragelaphini, and Giraffidae (H. mitchelli, H. okapiae, H. vegliai), and (4)
      geographically widespread species that are represented only by those that have
      been translocated with domestic stock. The North American fauna is characterized
      by 3 introduced and exotic species, H. placei, H. contortus, H. similis, which
      emphasizes the importance of continued documentation of faunal diversity in the
      context of predictive foundations derived from phylogenetic studies. Satellite
      associations for species of Haemonchus, particularly among Cervidae and Camelidae
      in the Neotropics and Cervidae, Antilocapridae, and possibly wild Caprinae in the
      Nearctic, have been a consequence of introductions and exchange of parasites at
      historical interfaces for managed and natural ecosystems. Such distributions are
      emblematic of the overriding significance of anthropogenic factors as
      determinants of the global distributions for pathogenic parasites in domestic and
      wild ruminants.

PMID- 15562610
TI  - A new pentastomid from the black vulture.
AB  - This article describes a new pentastomid species from the abdominal air sacs of a
      black vulture (Aegypius monachus Linnaeus, 1766) from central Spain. The
      parasite's morphological characteristics (as shown by light and scanning electron
      microscopy) suggest that it should be classified in the new genus. It is the
      third pentastomid species described in birds and the first for the Accipitridae.
      The mouth is almost terminal, there are 2 pairs of hooks behind the mouth, and
      the genital pore is immediately posterior to these structures, placing the new
      species within the Cephalobaenida. The anterior and posterior hooks are similar
      in size and are flanked by parapodial lob. Cuticular tubercles are absent, false
      annulations can be seen, and the parasite's eggs have 2 layers.

PMID- 15562611
TI  - Metaparasitylenchus hypothenemi n. sp. (Nematoda: Allantonematidae), a parasite
      of the coffee berry borer, Hypothenemus hampei (Curculionidae: Scolytinae).
AB  - Metaparasitylenchus hypothenemi n. sp. (Nematoda: Allantonematidae) is described
      from the coffee berry borer, Hypothenemus hampei (Ferrari) (Curculionidae:
      Scolytinae), in Chiapas, Mexico. This species differs from other members of the
      genus by its small size, annulated cuticle, lateral fields with 3 ridges, free
      living stages with an excretory pore located between the pharyngeal gland
      orifices, a distinct stylet with basal swellings in free-living females, a
      postvulval uterine extension, a thin stylet lacking basal swellings in males, 2
      separate spicules, a gubernaculum, and a peloderan bursa. Parasitic females are
      white, with a straight or slightly curved body and are ovoviviparous. Third-stage
      juveniles emerge from parasitized beetles and molt twice before reaching the
      adult stage. Because the coffee berry borer is the most important pest of coffee
      throughout the world and this parasite partially or completely sterilizes female
      beetles, it is worthy of further investigation as a potential biological control
      agent.

PMID- 15562612
TI  - Molecular phylogeny of the Haplosporidia based on two independent gene sequences.
AB  - The phylogenetic position of the Haplosporidia has confounded taxonomists for
      more than a century because of the unique morphology of these parasites. We
      collected DNA sequence data for small subunit (SSU) ribosomal RNA and actin genes
      from haplosporidians and other protists for conducting molecular phylogenetic
      analyses to help elucidate relationships of taxa within the group, as well as
      placement of this group among Eukaryota. Analyses were conducted using DNA
      sequence data from more than 100 eukaryotic taxa with various combinations of
      data sets including nucleotide sequence data for each gene separately and
      combined, as well as SSU ribosomal DNA data combined with translated actin amino
      acids. In almost all analyses, the Haplosporidia was sister to the Cercozoa with
      moderate bootstrap and jackknife support. Analysis with actin amino acid
      sequences alone grouped haplosporidians with the foraminiferans and cercozoans.
      The haplosporidians Minchinia and Urosporidium were found to be monophyletic,
      whereas Haplosporidium was paraphyletic. "Microcell" parasites, Bonamia spp. and
      Mikrocytos roughleyi, were sister to Minchinia, the most derived genus, with
      Haplosporidium falling between the "microcells" and the more basal Urosporidium.
      Two recently discovered parasites, one from abalone in New Zealand and another
      from spot prawns in British Columbia, fell at the base of the Haplosporidia with
      very strong support, indicating a taxonomic affinity to this group.

PMID- 15562613
TI  - Phylogenetic analysis on genera of Corallobothriinae (Cestoda: Proteocephalidea)
      from North American ictalurid fishes, using partial sequences of the 28s
      ribosomal gene.
AB  - Partial sequences of the 28S rDNA (ribosomal gene) were obtained from a total of
      11 populations of 5 species (in 3 genera) of North American corallobothriine
      proteocephalideans. These included Corallobothrium fimbriatum (3 populations),
      Corallobothrium parafimbriatum (1 population), Corallotaenia minutia (1
      population), Megathylacoides giganteum (2 populations), and Megathylacoides
      lamothei (4 populations). These sequences were used in a phylogenetic analysis to
      test the monophyly of Corallobothriinae and to investigate the interrelationships
      of the North American species. The results indicate that Corallobothriinae, as
      conventionally understood, is not monophyletic and that only the North American
      corallobothriines, parasites of ictalurid catfishes, form a monophyletic group.
      Corallobothrium parafimbriatum is sister taxon to a clade that includes
      Corallotaenia intermedia and C. minutia and not to its congener C. fimbriatum.
      Also, M. giganteum from Mexico appears to be more closely related to M. lamothei
      than to its conspecific in Canada. This and the amount of sequence divergence
      indicate possible cryptic speciation in its endemic host, the Lerma catfish,
      Ictalurus dugesi.

PMID- 15562614
TI  - Auriculostoma astyanace n. gen., n. sp. (Digenea: Allocreadiidae), from the
      banded astyanax, Astyanax fasciatus (Characiformes: Characidae), from Nicaragua,
      with a reevaluation of neotropical Crepidostomum spp.
AB  - Auriculostoma n. gen. (Trematoda: Allocreadiidae) is proposed for Auriculostoma
      astyanace n. sp. from the intestine of the characid fish Astyanax fasciatus in
      the Atlantic coastal drainages of Nicaragua. The new genus differs from all
      papillose allocreadiid genera, except Bunoderella, in possessing 2 pairs of
      muscular oral papillae (instead of 1 or 3), of which the ventrolateral pair is
      moderately developed and the dorsolateral papillae are long and auricular.
      Auriculostoma differs from Bunoderella Schell, 1964, in having lateral vitelline
      follicles, completely separated or confluent only in the posttesticular region, a
      uterus limited to the pretesticular region or with a few eggs at the level of the
      testes, and a long cirrus sac that overlaps the acetabulum or usually reaches
      posteriorly to the ovarian level. Three other allocreadiid species, all from
      South American freshwater fishes and each of which had previously been placed in
      Crepidostomum, are transferred to Auriculostoma based on the presence of the
      diagnostic muscular oral papillae. These include Crepidostomum platense Szidat,
      1954, C. macrorchis Szidat, 1954, and C. stenopteri Mane-Garzon and Gascon, 1973.
      Diagnostic features for Auriculostoma also include mainly pretesticular uterus,
      lateral vitellaria with variation in posttesticular confluence, and tandem
      testes. The genus appears to be typically associated with neotropical siluriforms
      (catfishes) and characiforms (tetras).

PMID- 15562615
TI  - Two species of Synhimantus (dispharynx) railliet, Henry and Sisoff, 1912
      (Nematoda: Acuarioidea: Acuariidae), in passerine birds from the Area de
      Conservacion Guanacaste, Costa Rica.
AB  - Members of 2 species of Synhimantus (Dispharynx) live under the lining of the
      gizzard in passerine birds from the Area de Conservacion Guanacaste, Costa Rica.
      Synhimantus (Dispharynx) nasuta (Rudolphi, 1819) occurs in Thraupis episcopus,
      Turdus grayi, Caryothraustes poliogaster, Platyrinchus cancrominus, Ramphocaenus
      melanurus, Vermivora peregrina, and Geothlypis poliocephala. A single male, in
      Turdus grayi, apparently representing a new species, distinguishable from all
      other species of Synhimantus (Dispharynx) by having similar shaped left and right
      spicules, is described but not named.

PMID- 15562616
TI  - The effects of parasite-derived immune-suppressive factors on the cellular innate
      immune and autoimmune responses of Drosophila melanogaster.
AB  - Immune-suppressive factors (ISFs) introduced into larvae of Drosophila
      melanogaster during infection by virulent endoparasitic wasps effectively block
      the innate immune response mediated by blood cells (hemocytes) but have little
      influence on the autoimmune response made by a tumor strain in which the blood
      cells manifest a similar response but instead target and destroy endogenous
      tissues. Quantitative hemocyte analyses indicate that ISFs interfere with the
      immune effector responses downstream of nonself recognition, hemocyte activation
      and differentiation, because these responses were manifested by tumor hosts, in
      which the parasitoids developed. The data suggest that once activated to
      encapsulate aberrant tissues, the target specificity of the autoimmune-activated
      hemocytes, and the genetic program underlying tumor formation, cannot be blocked
      by parasitoid-derived ISFs, which effectively inhibit identical hemocyte-mediated
      responses during parasitization.

PMID- 15562617
TI  - Quantification of Leishmania infantum parasites in tissue biopsies by real-time
      polymerase chain reaction and polymerase chain reaction-enzyme-linked
      immunosorbent assay.
AB  - Most of the experimental studies of Leishmania spp. infection require the
      determination of the parasite load in different tissues. Quantification of
      parasites by microscopy is not very sensitive and is time consuming, whereas
      culture microtitrations remain laborious and can be jeopardized by microbial
      contamination. The aim of this study was to quantify Leishmania infantum
      parasites by real-time polymerase chain reaction (PCR) using specific DNA TaqMan
      probes and to compare the efficacy of detection of this technique with a PCR
      enzyme-linked immunosorbent assay (ELISA). For this purpose, spleen and liver
      samples from L. infantum-infected mice were collected during a 3-mo longitudinal
      study and analyzed by both methods. PCR-ELISA failed to quantify Leishmania spp.
      DNA in samples with very low or very high numbers of parasites. Real-time PCR was
      more sensitive than PCR-ELISA, detecting down to a single parasite, and enabled
      the parasite quantification over a wide, 5-log range. In summary, this study
      developed a method for absolute quantification of L. infantum parasites in
      infected organs using real-time TaqMan PCR.

PMID- 15562618
TI  - Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human
      monocyte DNA topoisomerases I and II by antimonial drugs and classical
      antitopoisomerase agents.
AB  - We have compared the inhibitor sensitivities of DNA topoisomerase I (TOPI) from
      Leishmania donovani promastigotes and TOPs I and II of human monocytes using
      pentavalent and trivalent antimonials (SbV, SbIII) and classical TOP inhibitors.
      Bis-benzimidazoles (Hoechst-33258 and -33342) were potent inhibitors of both
      parasite and human TOPI, but Hoechst-33342 was markedly less cytotoxic to
      promastigotes than to monocytes in vitro. Leishmania donovani was also
      considerably less sensitive than monocytes to camptothecin, both at enzyme and
      cellular levels. Sodium stibogluconate (SSG) was the only antimonial to inhibit
      TOPI, exhibiting a significant (P < 0.05) 3-fold greater potency against the L.
      donovani enzyme but showed low cytotoxicities against intact promastigotes. The
      SbV meglumine antimoniate failed to inhibit TOPI and showed negligible
      cytotoxicities, whereas SbIII drugs were lethal to parasites and monocytes yet
      poor inhibitors of TOPI. Monocyte TOPII was inhibited by bis-benzimidazoles and
      insensitive to antimonials and camptothecin. The disparity between the high
      leishmanicidal activity and low anti-TOPI potency of SbIII indicates that in vivo
      targeting of L. donovani TOPI by the reductive pathway of antimonial activation
      is improbable. Nevertheless, the potent direct inhibition of TOPI by SSG and the
      differential interactions of camptothecin with L. donovani and human TOPI support
      the possibility of developing parasite-specific derivatives.

PMID- 15562619
TI  - Alternative mechanism of Eimeria bovis sporozoites to invade cells in vitro by
      breaching the plasma membrane.
AB  - In vitro Eimeria bovis sporozoites invade a wide range of cell types, and in the
      case of bovine cells, they may develop to first-generation schizonts. Often,
      however, they subsequently leave their host cell to invade a new one, which seems
      contrary to the classical way of infecting a cell by forming a parasitophorous
      vacuole. Using a standard, "cell wound assay," we show that E. bovis can invade
      bovine endothelial cells by breaching the plasma membrane and may again leave the
      surviving cell. Eimeria bovis sporozoites also infected VERO and HT29 cells but
      obviously without damaging the plasma membrane. The same held true when bovine
      endothelial cells were exposed to tachyzoites of Toxoplasma gondii and Neospora
      caninum. According to a literature report dealing with Plasmodium yoelii
      sporozoites, breaching the membrane of certain host cells may be a common
      phenomenon for coccidian sporozoites but may not be for merozoites.

PMID- 15562621
TI  - Observations on myiasis by the calliphorids, Bufolucilia silvarum and Bufolucilia
      elongata, in wood frogs, Rana sylvatica, from southeastern Wisconsin.
AB  - Larvae of certain species of blowflies (Calliphoridae) can cause myiasis in frogs
      and toads, but there are few reports from North American amphibians. Of these,
      most are from toads (bufonids). In this study, we observe primary myiasis in a
      population of juvenile wood frogs, Rana sylvatica, collected on 22-23 August
      2003, from southeastern Wisconsin and compare our observations with previous
      studies on myiasis from toads. Two (5%) of 39 frogs were infected by the blow fly
      Bufolucilia silvarum, with an intensity of 28 and 31, whereas 1 (2.5%) of 39
      frogs was infected by the blow fly Bufolucilia elongata with an intensity of 14.
      We found that (1) B. silvarum lay eggs on healthy wood frogs, (2) eggs hatch,
      with first-instar maggots penetrating under the skin, (3) maggots develop to
      mature third instars within 13-16 hr of egg hatching, (4) maggots kill the host
      within 7-47 hr of egg hatching, and (5) maggots consume the entire frog carcass
      reducing it to bones within 42-59 hr of egg hatching. Our observations on the
      time of death and how quickly carcasses of wood frogs were consumed by these
      maggots compared with previous studies on toads suggest that finding infected
      juvenile wood frogs may be uncommon. Therefore, myiasis by these flies on wood
      frogs and other small terrestrial anurans may be a phenomenon that is much more
      common than is currently observed. This is the first report of B. silvarum and B.
      elongata causing myiasis in wood frogs.

PMID- 15562620
TI  - A focus of human infection by Haplorchis taichui (Trematoda: Heterophyidae) in
      the southern Philippines.
AB  - We report an exceptionally high rate of infection by Haplorchis taichui
      (Nishigori, 1924) in human populations on Mindanao Island, southern Philippines.
      This intestinal fluke is seldom encountered, and this is the first report of high
      prevalence of infection (36%) in humans by H. taichui in the Philippines. The
      likely source of haplorchine infection has been linked to consumption of raw or
      undercooked freshwater fish containing infective metacercariae. The most common
      clinical symptoms appeared as upper abdominal discomfort or pain and borborygmi.
      Praziquantel (75 mg/kg divided in 3 doses in 1 day) was a well-tolerated and
      effective treatment for infection by H. taichui.

PMID- 15562622
TI  - Biologic and molecular characteristics of Toxoplasma gondii isolates from striped
      skunk (Mephitis mephitis), Canada goose (Branta canadensis), black-winged lory
      (Eos cyanogenia), and cats (Felis catus).
AB  - Toxoplasma gondii isolates can be grouped into 3 genetic lineages. Type I
      isolates are considered virulent to outbred mice, whereas Type II and III
      isolates are not. In the present report, viable T. gondii was isolated for the
      first time from striped skunk (Mephitis mephitis), Canada goose (Branta
      canadensis), and black-winged lory (Eos cyanogenia). For the isolation of T.
      gondii, tissues were bioassayed in mice, and genotyping was based on the SAG2
      locus. Toxoplasma gondii was isolated from 3 of 6 skunks, 1 of 4 Canada geese,
      and 2 of 2 feral cats (Felis catus) from Mississippi. All donor animals were
      asymptomatic. Viable T. gondii was also isolated from 5 of 5 lories that had died
      of acute toxoplasmosis in an aviary in South Carolina. Genotypes of T. gondii
      isolates were Type III (all skunks, lories, and the goose) and Type II (both
      cats). All 5 Type III isolates from birds and 2 of the 3 isolates from skunks
      were mouse virulent.

PMID- 15562623
TI  - Molecular and biological characterization of Hammondia heydorni-like oocysts from
      a dog fed hearts from naturally infected white-tailed deer (Odocoileus
      Virginianus).
AB  - Neospora caninum and Hammondia heydorni are morphologically and phylogenetically
      related coccidians that are found in dogs. Although there is serological evidence
      of N. caninum infection in the white-tailed deer (Odocoileus virginianus), the
      parasite has not been yet isolated from the tissues of this host. In an attempt
      to isolate N. caninum from deer, hearts from 4 deer with antibodies to N. caninum
      were fed to 2 dogs. One of these dogs shed unsporulated oocysts 12-14 microm in
      diameter. Sporulated oocysts were not infective to Mongolian gerbils (Meriones
      ungulatus), and DNA isolated from these oocysts was not amplified using N.
      caninum-specific primers. However, positive amplification with the H. heydorni
      specific first internal transcribed spacer (ITS-1) primers and common
      toxoplasmatiid ITS-1 primers confirmed the presence of H. heydorni DNA in the
      samples. The oocysts were considered to be H. heydorni on the basis of their
      morphology, biology, and molecular characteristics. This is the first record of a
      H. heydorni-like parasite in the white-tailed deer.

PMID- 15562624
TI  - Ingestion of Cryptosporidium oocysts by Caenorhabditis elegans.
AB  - Cryptosporidium parvum has been associated with outbreaks of human illness by
      consumption of contaminated water, fresh fruits, and vegetables. Free-living
      nematodes may play a role in pathogen transmission in the environment.
      Caenorhabditis elegans is a free-living soil nematode that has been extensively
      studied and serves as a good model to study possible transmission of C. parvum
      oocysts that may come into contact with produce before harvest. The objective of
      this study was to determine whether C. elegans could serve as a potential
      mechanical vector for transport of infectious C. parvum and Cyclospora
      cayetanensis in agricultural settings and whether C. elegans could ingest,
      excrete, and protect oocysts from desiccation. Seventy to 85% of worms ingested
      between 0 and 500 oocysts after 1 and 2 hr incubation with oocysts. Most of the
      nematodes ingested between 101 and 200 oocysts after 2 hr. Intact oocysts and
      empty shells were excreted by nematodes. Infectivity was determined by the
      neonatal assay with different treatments of worms (intact or homogenized) or
      oocysts or both. Adult C. elegans containing C. parvum kept in water were
      infective for mice. In conclusion, C. elegans adults can ingest and excrete C.
      parvum oocysts. Caenorhabditis elegans containing C. parvum oocysts can infect
      mice but does not seem to protect oocysts from extreme desiccation at 23 C
      incubation of a day or longer. Cyclospora oocysts were not ingested by C.
      elegans. The role of free-living nematodes in produce contamination needs to be
      further examined.

PMID- 15562625
TI  - Protection of calves against cryptosporiosis by oral inoculation with gamma
      irradiated Cryptosporidium parvum oocysts.
AB  - The purpose of this study was to determine whether gamma-irradiated
      Cryptosporidium parvum oocysts could elicit protective immunity against
      cryptosporidiosis in dairy calves. Cryptosporidium parvum Iowa strain oocysts (1
      x 10(6) per inoculation) were exposed to various levels of gamma irradiation (350
      500 Gy) and inoculated into 1-day-old dairy calves. The calves were examined
      daily for clinical signs of cryptosporidiosis, and fecal samples were processed
      for the presence of C. parvum oocysts. At 21 days of age, the calves were
      challenged by oral inoculation with 1 x 10(5) C. parvum oocysts and examined
      daily for oocyst shedding and clinical cryptosporidiosis. Calves that were
      inoculated with C. parvum oocysts exposed to 350-375 Gy shed C. parvum oocysts in
      feces. Higher irradiation doses (450 or 500 Gy) prevented oocyst development, but
      the calves remained susceptible to C. parvum challenge infection. Cryptosporidium
      parvum oocysts exposed to 400 Gy were incapable of any measurable development but
      retained the capacity to elicit a protective response against C. parvum
      challenge. These findings indicate that it may be possible to protect calves
      against cryptosporidiosis by inoculation with C. parvum oocysts exposed to 400-Gy
      gamma irradiation.

PMID- 15562626
TI  - Evaluation of the presence of a thapsigargin-sensitive calcium store in
      trypanosomatids using Trypanosoma evansi as a model.
AB  - Ca2+ plays an important role in the regulation of several important activities in
      different trypanosomatids. These parasites possess a Ca2+ transport system in the
      endoplasmic reticulum (ER) involved in Ca2+ homeostasis, which has been reported
      to be insensitive to thapsigargin, a classical inhibitor of the sarcoplasmic-ER
      Ca2+ adenosine triphosphatase (ATPase) (SERCA) in most eukaryotic cells. However,
      currently there is a controversy regarding the existence of a thapsigargin
      sensitive ER Ca2+ store in these parasites. Therefore, we decided to explore the
      effect of this inhibitor using different methodological approaches. First, we
      selected Trypanosoma evansi as a parasite model to warrant the homogeneity of the
      population because this parasite has only a single life cycle, i.e., bloodstream
      form trypomastigotes. Second, we compared the thapsigargin effect on Ca2+
      homeostasis by spectrophotometrical Ca2+ measurements using 3 different
      approaches: whole-cell populations, cells that have been permeabilized by
      treatment with digitonin, and intact single cells. Our results demonstrate that a
      low concentration of thapsigargin induces Ca2+ release from intracellular Ca2+
      stores in this parasite, which can be observed independently of the method used.
      Furthermore, the addition of thapsigargin before or after nigericin did not
      abolish its effect, showing that thapsigargin acts specifically on the ER. In
      conclusion, our results indicate the presence of a nonmitochondrial thapsigargin
      sensitive Ca2+ store in T. evansi.

PMID- 15562627
TI  - Exogenous nucleosides are required for the morphogenesis of the human filarial
      parasite Brugia malayi.
AB  - The nematode parasites Wuchereria bancrofti, Brugia malayi, and B. timori cause a
      human disease known as lymphatic filariasis, which afflicts approximately 120
      million people worldwide. The parasites enter the human host from the mosquito as
      L3 or infective larvae and subsequently differentiate through 2 molts. In this
      communication, I report that B. malayi and B. pahangi depend on an exogenous
      source of at least 1 purine and 1 pyrimidine nucleoside to complete the L3 to L4
      molt. The requirement for exogenous nucleosides opens the door for possible
      chemotherapeutic intervention.

PMID- 15562628
TI  - Observations on the leech Placobdella ornata feeding from bony tissues of
      turtles.
AB  - The leech Placobdella ornata was observed feeding from the blood sinuses of the
      plastron and carapace bones of Chelydra serpentina and Chrysemys picta. Evidence
      of successful feeding included blood upwelling from the point of attachment and
      gastric ceca of the leeches freshly filled with blood after removal. There was an
      apparent preference for the sulci between scales of the shell.

PMID- 15562629
TI  - Trypanosoma brucei: unexpected azide sensitivity of bloodstream forms.
AB  - Bloodstream forms of Trypanosoma brucei lack cytochromes and are, therefore,
      insensitive to cyanide. Azide is a toxic anion that bears chemical and biological
      properties in common with cyanide and may act in a similar way by inhibition of
      cytochrome c oxidase. It was, therefore, surprising to find that bloodstream
      forms of T. brucei are sensitive to azide; growth is reduced by 50% with 0.1 mM
      azide. So far, the only enzyme known in bloodstream forms of T. brucei to be
      sensitive to azide is the iron-containing superoxide dismutase. However, because
      the activity of the superoxide dismutase was not affected in parasites incubated
      for 16 hr with 0.5 mM azide (a concentration at which no cell proliferates), the
      toxic action of azide cannot be due to inhibition of this enzyme. These results
      indicate that the general toxicity of azide is different from that of cyanide.

PMID- 15562630
TI  - Identification of the copepod intermediate host of the introduced broad fish
      tapeworm, Diphyllobothrium latum, in Southern Chile.
AB  - The broad fish tapeworm, Diphyllobothrium latum, is an exotic species in both
      Chile and Argentina, and until now, its copepod host has remained unknown in
      South American waters. The objective of this study was to identify calanoid
      copepod species that may be intermediate hosts for D. latum in Lake Panguipulli,
      Chile. In this lake, the highest levels of infection by this tapeworm occur in
      the introduced rainbow trout, Oncorhynchus mykiss. Of the 2 calanoid copepods
      found in Lake Panguipulli, Diaptomus diabolicus and Boeckella gracilipes, only D.
      diabolicus became infected on experimental exposure to coracidia. Prevalence
      (mean intensity) of experimental infection in adult copepods was 73.2% (2.8
      procercoids per host). Diaptomus diabolicus has been demonstrated to be a new
      intermediate host; this is the first record of a copepod host for D. latum in
      South America.

PMID- 15562631
TI  - Alteration of antibodies against the fifth-stage larvae and changes in brain
      magnetic resonance images in experimentally infected rabbits with Angiostrongylus
      cantonensis.
AB  - Magnetic resonance (MR) imaging has been suggested to be helpful in delineating
      the lesions during the acute phase of angiostrongyliasis caused by
      Angiostrongylus cantonensis. In this study, antibody titers in serum samples of 3
      rabbits were determined by enzyme-linked immunosorbent assay, and brain MR images
      were obtained from 6 rabbits. The antibody titer elevated rapidly in the first 4
      wk postinfection (PI) before reaching a plateau. However, suspicious changes in
      brain MR images near the left lateral ventricle and hippocampus were found only
      in 1 rabbit on day 28 PI. These findings indicate that immunologic responses in
      the central nervous system at the early stage of angiostrongyliasis are not
      sufficient to be observed by image studies.

PMID- 15562632
TI  - Possible association between passive smoking and lower exhaled nitric oxide in
      asthmatic children.
AB  - In adults, both active and passive smoking reduce levels of exhaled nitric oxide
      (eNO); however, to date, passive exposure to environmental tobacco smoke (ETS)
      has not been shown to affect eNO in children. The authors recruited 174 asthmatic
      children (96 male, 78 female) and 79 nonasthmatic controls (46 male, 33 female)
      from a group of children aged 5 to 14 yr who attended a children's hospital for
      an outpatient visit or elective surgery. Each subject's exposure to ETS was
      ascertained by questionnaire, and their eNO levels were measured. Asthmatic
      children had higher eNO levels (ppb) than nonasthmatic children (p = 0.04), and
      asthmatic children exposed to ETS had significantly lower eNO levels than
      unexposed children (p = 0.005). Exposure to ETS did not alter eNO levels in
      nonasthmatic children (p = 0.4). Results of the study suggest that ETS exposure
      is associated with lower eNO levels among childhood asthmatics. Consequently, ETS
      exposure may need to be considered when physicians interpret eNO levels in
      asthmatic children. Further study of the effects of ETS on eNO levels is
      recommended.

PMID- 15562633
TI  - Air pollution and hospital admissions for ischemic heart diseases among
      individuals 64+ years of age residing in Seoul, Korea.
AB  - There is increased evidence that air pollution may be associated with
      cardiovascular disease. The authors' prior investigations on the association
      between air pollution exposure and stroke mortality led to the current study,
      which was conducted to assess the effects of ambient air pollution on ischemic
      cardiovascular diseases among the elderly population (i.e., males and females 64+
      yr of age) in Seoul, Korea. The authors estimated the relative risks of
      hospitalization associated with an interquartile range (IQR) increase in
      pollution concentrations; a generalized additive Poisson model was used to
      conduct a time-series analysis of the counts. The concentrations of ambient air
      pollutants were lower than the current recommendations for air quality in Korea.
      The estimated relative risks of hospitalization associated with an IQR were 1.05
      (95% confidence interval [CI] = 1.01, 1.10) for particulate matter less than or
      equal to 10 microm in diameter (PM10) (IQR = 40.4 microg/m3); 1.10 (95% CI =
      1.05, 1.15) for ozone (IQR = 21.7 ppb); 1.08 (95% CI = 1.03, 1.14) for nitrogen
      dioxide (IQR = 14.6 ppb); 1.07 (95% CI = 1.01, 1.13) for carbon monoxide (IQR =
      1.0 ppm); and 0.95 (95% CI = 0.90, 1.01) for sulfur dioxide (IQR = 4.4 ppb). The
      authors observed that sulfur dioxide was a significant risk factor for ischemic
      heart disease-related hospital admissions during the summer months (i.e., June,
      July, and August) (relative risk = 1.32; 95% CI = 1.08, 1.62). Hospital
      admissions for ischemic heart diseases were associated significantly with daily
      variations in levels of ambient air pollutants. These findings may provide new
      insights into the possible pathologic mechanisms involving air pollutants, and
      they support the hypothesis that the elderly appear to be at particular risk from
      the effects of air pollution, at pollutant levels lower than the standards
      commonly adopted by many countries.

PMID- 15562634
TI  - Relationship between concentration of pyrene and aerosol size distribution in
      traffic exhausts in Taipei, Taiwan.
AB  - Variations in pyrene concentrations in motor-vehicle emissions were assessed on
      the basis of aerodynamic particle size and by the type of vehicle (i.e., car,
      truck, or bus) that passed through a Taipei, Taiwan, highway toll station.
      Airborne particles were collected with 8-stage cascade samplers equipped with 34
      mm polyvinyl chloride filters and located in the breathing zones of toll-station
      workers. The authors used gas chromatography/mass spectrometry to analyze 22
      polycyclic aromatic hydrocarbons that were collected. The absolute concentration
      of pyrene was highest in the fine-particle emission fraction for trucks, buses,
      and passenger cars; however, fine particles in truck and bus exhausts contained
      higher pyrene concentrations than the corresponding size fraction of particles
      emitted from passenger cars. Truck and bus emissions contained a higher
      concentration of pyrene than car emissions because trucks and buses produced
      greater amounts of fine and coarse particles, and their fine particles contained
      higher concentrations of pyrene.

PMID- 15562635
TI  - Symptoms of mothers and infants related to total volatile organic compounds in
      household products.
AB  - The authors sought to determine whether reported symptoms of mothers and infants
      were associated significantly with the use of household products that raised
      indoor levels of total volatile organic compounds (TVOCs). Data collected from
      170 homes within the Avon Longitudinal Study of Parents and Children (ALSPAC: a
      large birth cohort of more than 10,000) had determined which household products
      were associated with the highest levels of TVOCs. The latter data were collected
      over a period that approximated 6 mo of pregnancy and the infants' first 6 mo of
      life. This paper presents (a) the mothers' self-reports of the use of these
      products in their homes and (b) self-reported medical symptoms of mothers and
      infants postnatally. Higher TVOC levels were associated with air freshener and
      aerosol use. Infant diarrhea and earache were statistically significantly
      associated with air freshener use, and diarrhea and vomiting were significantly
      associated with aerosol use. Headache experienced by mothers 8 mo after birth was
      significantly associated with the use of air fresheners and aerosols; maternal
      depression was significantly associated with the use of air fresheners. The
      results of the study suggest a link between the use of products that raise indoor
      levels of TVOCs and an increased risk of certain symptoms among infants and their
      mothers.

PMID- 15562636
TI  - Mortality among a cohort of female farm residents in New York State.
AB  - A retrospective cohort study of mortality among 6,405 female farm residents who
      were New York Farm Bureau members, or spouses or relatives of members, was
      conducted from 1980 through 1993. Similar to previous findings for male farmers,
      the cohort experienced significantly lower mortality rates for all causes
      combined (including malignant neoplasms and cardiovascular disease), compared
      with rural nonfarm female residents. These findings suggest that farmers and farm
      residents of both genders have favorable habits with respect to several lifestyle
      factors. The results of this study were consistent with those from other studies
      of farm populations worldwide.

PMID- 15562637
TI  - Evidence for increased risks of preterm delivery in a population residing near a
      freeway in Taiwan.
AB  - Traffic emissions are a major source of air pollution in urban areas. The results
      of recent studies have suggested that air pollution may be related to adverse
      pregnancy outcomes such as low birth weight and preterm delivery. The authors
      investigated the association between traffic-related air pollution and preterm
      deliveries. The study group included all first-parity singleton live births that
      occurred during 1992-1997 to women who lived in a zone along the Zhong-Shan
      Freeway in Taiwan (N = 6,251). The zone was defined as areas 1,500-m wide on
      either side of the freeway; it was located in the San-Ming, Nan-Tzu, Chienchen,
      and Linya wards-all of which are residential areas in East Kaohsiung. The
      prevalence of deliveries of preterm birth infants was significantly higher among
      mothers who lived within 500 m of the freeway than among mothers who resided 500
      1,500 m from the freeway. In their analysis, the authors controlled for several
      confounders (e.g., maternal age, season, marital status, maternal education,
      infant gender). The adjusted odds ratio was 1.30 (95% confidence interval = 1.03,
      1.65) for delivery of preterm infants born to mothers who lived within 500 m of
      the freeway. Such data provide additional support for the hypothesis that air
      pollution can affect the outcome of pregnancy.

PMID- 15562638
TI  - Use of instrumental neutron activation analysis to determine concentrations of
      multiple trace elements in human organs.
AB  - AInasmuch as the availability of suitable analytical specimens may be limited,
      the defining of normal concentrations or ranges of trace elements in human organs
      is problematic. Little is known about whether various parts of an organ, or of
      bilateral organs, differ in their concentrations of trace elements. In this
      study, the authors determined the distribution of trace elements in different
      portions of human organs, and between the right and left lung and kidney, with
      instrumental neutron activation analysis (INAA). By setting the variance limit at
      less than 20%, they determined that trace elements were similar in 7 of the 9
      organs tested (the exceptions being kidney and lung). Trace element
      concentrations found in the right lung were very different from those found in
      the left lung. Some trace elements varied in concentration according to the part
      or laterality of the organ tested.

PMID- 15562639
TI  - Asbestos exposure and antineutrophil cytoplasmic Antibody (ANCA) positivity.
AB  - The authors used indirect immunofluorescence to examine the association of
      antineutrophil cytoplasmic antibodies (ANCAs) with exposure to asbestos among 61
      asbestos-exposed patients (mean exposure = 24.6 yr) and 39 nonexposed controls.
      ANCA positivity was detected significantly more frequently (p = 0.034) in the
      asbestos-exposed group (21.3%) than in the control group (5.1%). ANCA-associated
      diseases did not occur more frequently among subjects exposed previously to
      asbestos than among unexposed controls. These findings confirmed that exposure to
      asbestos is another occupational factor, as is silica exposure, that is
      associated with ANCA positivity. The influence of asbestos appears stronger than
      that of silica because ANCA positivity was found among subjects who had histories
      of exposure to asbestos but who did not exhibit typical radiographic signs of
      asbestosis on their chest x-rays. Additional stimuli may be necessary to induce
      systemic vasculitis in asbestos-exposed persons.

PMID- 15562640
TI  - [Study on the characteristics of apoptosis in the condyles of osteoarthritic
      temporomandibular joints].
AB  - OBJECTIVE: To study the characteristics of apoptosis in the condyles of
      osteoarthritic temporomandibular joints, and investigate its role in the
      pathogenesis of the disease. METHODS: Temporomandibular joint osteoarthrosis
      model of rabbits was created by partial resection of joint disc. The animal
      models were sacrificed in the 15th day, the 1st month, the 2nd month, the 3rd
      month, the 4th month, the 5th month, and the 6th month chronologically. Then the
      pathological condyles were sectioned and detected with TUNEL method to
      investigate the apoptosis within the tissue. RESULTS: In the reactive repairing
      state of osteoarthrosis, the apoptosis cells mainly located in the superficial
      fibrous layer of articular cartilage. With the remodeling of articular cartilage
      and bone, the apoptosis cells gradually appeared in the proliferating layer,
      especially in the "clusters of chondrocytes". Accompanied with the severe damage
      and loss of articular cartilage, the phenomena of apoptosis decreased in the
      lower zone of cartilage and increased in the hypertrophic and calcified zone.
      CONCLUSION: There were abundant phenomena of apoptosis within the condylar
      cartilage of osteoarthritic temporomandibular joint. Abnormal proliferation and
      abundant apoptosis would disturb the regulation mechanism in the cartilage matrix
      and lead to the osteoarthrosis.

PMID- 15562641
TI  - [Intervention effect of an inducible nitric oxide synthase inhibitor on
      carcinogenesis of hamster cheek pouch carcinoma].
AB  - OBJECTIVE: To observe the expression changes of VEGF, iNOS and the level of MVD
      and NO during the evolution of Golden hamster cheek pouch carcinogenesis. To
      study the effect of NO in carcinogenesis in the pouch of hamster, and to
      investigate the effect of NOS inhibitor L-NAME in interfering with
      carcinogenesis. METHODS: 90 golden hamsters were divided into three groups: 40 in
      experiment group, 40 in control group and 10 in blank group. DMBA was painted on
      hamster's cheek pouch in experiment and control group, L-NAME was given to
      hamster in experiment group at the dose of 0.02 ml/g. Hamsters were killed at 6,
      9, 12 and 16th weeks, respectively. The blank group was killed at the 16th week.
      SABC immunohistochemistry assay was used to detect the expression of iNOS, VEGF
      and factor VIII-related antigen. MVD was measured. The level of NO was measured
      by Spectrophotometry. RESULTS: The difference between control group and
      experiment group at the 12th week and 16th week was observed. The difference of
      positive expression rate of iNOS in all group was significant and difference
      between blank group and control group was significant. The difference of positive
      expression rate of VEGF in all group was significant and difference between blank
      group and control group at the 12th and 16th week was significant; there was
      significant difference in every group MVD from the 6th week control group to the
      16th week control. There were significant difference among the control group,
      except the 6th week of experiment and control group. CONCLUSION: There is an
      increased expression of iNOS and the level of NO, as well MVD during the
      evolution of Golden hamster cheek pouch carcinogenesis from slightly dysplasia to
      invasive carcinoma. NO plays an important role during the evolution of
      carcinogenesis, and iNOS inhibitor L-NAME can inhibit the carcinogenesis.

PMID- 15562642
TI  - [An experimental study on PLGA carrier for oral tissue engineered mucosa by
      subcutaneous implantation in rabbits].
AB  - OBJECTIVE: To look for the best carrier for cultivating oral tissue engineered
      mucosa. METHODS: A series of membrane of scaffold materials of polycleclide-co
      plycoclide (PLGA) were studied on their weight and biocompatibility after they
      had been implanted subcutaneously in rabbits for 1, 2, 3, 4 weeks respectively.
      RESULTS: PLGA I , II, III degraded completely in rabbits after 2, 3, 4 weeks
      respectively. The other PLGA membrane degraded about 50% after 4 weeks.
      Histologically, the reactions of PLGA I, II, III with surrounding tissues were
      normal and membranes had a good biocompatibility. CONCLUSION: The biodegrading
      rate of PLGA II is suitable for clinic practice. PLGA II was a promising carrier
      for oral tissue-engineered mucosa due to its excellent biocompatibility and
      biodegrading rate.

PMID- 15562643
TI  - [Insulin-like growth factor-II and basic fibroblast growth factor affect
      periodontal ligament cells expressing osteoprotegerin in vitro].
AB  - OBJECTIVE: This study was carried out to investigate the effects of insulin-like
      growth factor-II (IGF-II) and basic fibroblast growth factor (bFGF) on
      osteoprotegerin (OPG) secretion of periodontal ligament cells (PDLCs). METHODS:
      Healthy human premolars extracted for orthodontic reasons from 12-14 years old
      donators were obtained, and periodontal tissues were collected and cultured to
      obtain PDL cells. Primary or first passage PDLCs were cloned by means of limited
      dilutions. PDLCs with osteoblastic phenotypes were characterized as follows:
      Alkaline phosphatase activity, collagen III production and bone-like nodules
      formation. IGF-II and bFGF were added into culture media and their effects on
      PDLCs proliferation and OPG secretion were observed. The OPG concentrations in
      cell culture supernatants were detected by sandwich ELISA. Living cell numbers
      were demonstrated by MTT test. The average levels of OPG secretion by a single
      cell were calculated by dividing OPG concentration with MTT-test result. RESULTS:
      Both IGF-II and bFGF upregulated the mtt values (P < 0.05), but ICF-II
      downregulated the opg/mtt values (P < 0.05), whereas bFGF had no significant
      effect on opg/mtt values (P > 0.05). CONCLUSION: IGF-II enhances the
      proliferation of PDL cells but prohibits OPG secretion. Although bFGF has the
      same effect on the proliferation of PDL cells, it has no effect on OPG secretion.
      Before cytokines were used to enhance periodontal regeneration, their effects on
      local bone balance should also be studied.

PMID- 15562644
TI  - [The effects of growth hormone on rabbit's mandibular condylar chondrocytes
      proliferation and secretion in vitro].
AB  - OBJECTIVE: To study the effect of growth hormone (GH) on the proliferation and
      type II collagen secretion of chondrocytes of mandibular condyle in rabbit in
      vitro. METHODS: Flow cytometry (FCM) and immunohistochemical technique were
      employed to observe the possible changes. RESULTS: (1) The exogenic GH can
      enhance the proliferation and synthesis of DNA of the chondrocytes of mandibular
      condyle in rabbit in vitro. The suitable concentration of GH is 10 microg/ml. The
      synthesis of DNA reaches the highest level after 12 hours, while the
      proliferation index (PI) hits the highest after 24 hours. (2) GH (10 microg/ml)
      can stimulate the secretion of type II collagen of the chondrocytes. CONCLUSION:
      The exogenic GH can enhance the proliferation, the synthesis of DNA and the
      secretion of type II collagen of the chondrocytes of mandibular condyle in rabbit
      in vitro.

PMID- 15562645
TI  - [Studies on the transfection of umbilical endothelia with catalytic subunit of
      telomerase].
AB  - OBJECTIVE: To investigate the variety of proliferating ability of umbilical
      endothelia (UE) transfected by plasmid pBABE-HYGR-hTERT. METHODS: UE was
      identified from two aspects: morphology and CD34 labeling technique. The plasmid
      was obtained and identified by alkali splitting and gel electrophoresis.
      Liposomes were used to transfect UE. RT-PCR based telomeric repeat amplification
      protocol (TRAP) assay was used to measure the telomerase activity of endothelia.
      RESULTS: UE arranged as "cobblestone" and were positive of CD34 labeling.
      Endothelia transfected by pBABE-HYGR-hTERT(HC) had an raised absorbance of 0.889.
      The shape of growth curve of HC was similar to UE. But the absorbance of MTT test
      and the amount of HC were prior to UE at every measuring time and the amount of
      HC increased four times within 8 days (P < 0.05). CONCLUSION: The transfection of
      pBABE-HYGRO-hTERT had greatly improved the proliferating abilities and activated
      the telomerase of UE.

PMID- 15562646
TI  - [Biological effects of tetracycline on cultured human periodontal fibroblasts].
AB  - OBJECTIVE: To explore the biological effects of tetracycline on cultured human
      periodontal ligament fibroblasts (HPDLFs). METHODS: Increasing concentrations of
      tetracycline (1, 5, 20, 100, 500, 2500 microg/ml) were added to the medium of
      cultured HPDLFs, respectively. After co-incubated for 2 days, cell morphology was
      observed under reverse microscope, meanwhile, cell proliferation activity was
      assayed using MTT, the total amount of protein was detected with Coumassie Bright
      Blue method and DNA synthesis was measured by 3H-TdR. RESULTS: Over a
      concentration range of 1 to 100 microg/ml, cells demonstrated a normal
      appearance, spindle or fusiform shaped. Moreover, at a concentration range of 20
      to 100 microg/ml, tetracycline significantly enhanced the proliferating activity
      and biosynthesis of HPDLFs (P < 0.01). However, higher concentration (2500
      microg/ml) not only changed cell morphology, but also significantly inhibited
      cellular activity. CONCLUSION: The results suggested that proper doses of
      tetracycline could promote proliferation and biosynthesis of HPDLFs while higher
      concentrations of tetracycline had cytotoxic effect.

PMID- 15562647
TI  - [Changes of profile prominence in borderline cases with extraction and non
      extraction orthodontic treatment].
AB  - OBJECTIVE: To compare the treatment effect on the prominence of profile in
      borderline cases between extraction and non-extraction treatment. METHODS: The
      sample consisting of 33 borderline cases based on the judgment of 5 orthodontic
      specialists was divided into three groups according to the treatment way selected
      by the doctor in charge of the case. Three groups comprised 12 non-extraction
      cases, 13 four first premolars extraction cases and 8 four second premolars
      extraction cases. Structure superimposition was used to measure landmarks
      displacements which reflect the change of profile prominence before and after
      orthodontic treatment using pretreatment FH plane as a frame of reference.
      RESULTS: Only the prominence of upper and lower incisors showed statistically
      significance between the extraction and non-extraction treatments. There was no
      statistically significant difference between the extraction of four first
      premolars and second premolars. CONCLUSION: The main effect of extraction vs. non
      extraction on profile of borderline cases is the prominence of upper and lower
      incisors, while their influences on upper and lower base bone and soft-tissue
      profile are not obvious.

PMID- 15562648
TI  - [Determination and analysis of masticatory performance of nonfree-end removable
      partial denture].
AB  - OBJECTIVE: The purpose of this study was to evaluate the changes of masticatory
      performance of the cases wearing dentures and relative factors. METHODS: The
      changes of masticatory performance of the cases wearing dentures were studied
      before and after wearing by using the light absorption method and peanuts as test
      food. RESULTS: The mastication performance of the experimental groups was
      predominantly lower than that of the control groups. The masticatory performance
      was gradually improved with wearing denture period increasing. Factors relating
      to the masticatory performance were age, number of occlusal units lost and the
      kind of denture, and the number of chewing etc. CONCLUSION: The mastication
      performance of the experimental groups was dominantly lower than that of the
      control groups, but gradually improved with wearing denture period increasing.
      Varied factors affect the masticatory performance of experimental groups.

PMID- 15562649
TI  - [Anesthetic efficacy of 2% mepivacaine in conservative dentistry].
AB  - OBJECTIVE: To determine the efficacy of 2% mepivacaine in conservative dentistry.
      METHODS: The patients who needed cavity preparation or access to pulp chamber
      received local infiltration with 2% mepivacaine. Anesthesia time, anesthetic
      efficacy and cardiovascular system influences were assessed. 3% lidocaine with
      epinephrine served as control. RESULTS: In experiment group, the anesthesia
      effects were quicker and anesthesia duration was longer than that in control
      group. Doctors highly appreciated the anesthetic efficacy. Two groups did not
      show any evident change in blood pressure and heart rate. CONCLUSION: 2%
      mepivacaine is a safe and efficacious local anesthetic drug in conservative
      dentistry.

PMID- 15562650
TI  - [Study on reference value of healthy teeth mobility of youth].
AB  - OBJECTIVE: This study aimed to establish the reference value range of healthy
      teeth mobility in Chinese youth. METHODS: 200 right side teeth of Han nationality
      of Chinese youths were measured so as to get the range of the parameters.
      RESULTS: All parameters of 14 teeth were achieved. The parameter of TM in
      mandibular incisor was the highest and in mandibular first molar lowest.
      CONCLUSION: It is very significant to get and quantify the healthy teeth's
      parameter range. Because they can be served as the healthy contrast when dentists
      diagnose the mobility. It also reflects the fact that lower the TM parameter is,
      firmer the tooth will be.

PMID- 15562651
TI  - [The survey of prosthetic treatment in the elderly].
AB  - OBJECTIVE: To acquire teeth and prosthetic conditions of the elderly. METHODS:
      1166 patients of over 60 years old had been given prosthetic treatment, and the
      teeth conditions were analyzed. RESULTS: The average number of missing teeth was
      10.25. The maxillary missing teeth were more than mandibular ones. The rate of
      missing teeth were as follows: maxillary teeth > mandibular teeth; molars >
      bicuspids > incisors > cuspid. 1120 cases were treated with removable dentures.
      59% of the removable partial dentures had free-end saddles. 46 cases were treated
      with fixed bridges. CONCLUSION: The characteristics of prosthetic patients in the
      elderly were as follows: a large number of missing teeth and free-end missing
      teeth, attrition of resident teeth, food impaction, existing-residual root and
      loosen teeth. Removable denture was the main method of the prosthetic therapy for
      the elderly patients. Fixed bridge was used when the patient condition was good.
      The cuspid, treated residual root and the third molar should be used for the
      retention and support of the prosthesis.

PMID- 15562652
TI  - [Clinical multi-manifestation, diagnosis and treatment of non-Hodgkin's lymphoma
      in oral, maxillofacial and cervical regions].
AB  - OBJECTIVE: To investigate the clinical multimanifestation, diagnosis and
      treatment of non-Hodgkin's lymphoma in oral, maxillofacial and cervical regions.
      METHODS: 58 cases of non-Hodgkin's lymphoma in oral, maxillofacial and cervical
      regions were retrospected in this study. RESULTS: The manifestation of 58 cases
      was complicated. Non-Hodgkin's lymphoma treatment was synthetical therapy or
      chemical therapy. CONCLUSION: Non-Hodgkin's lymphoma in oral, maxillofacial and
      cervical regions had multi-manifestation and higher malignant. The final
      diagnosis relied on pathological examination. Both of sythetical therapy and
      chemical therapy were effective to non-Hodgkin's lymphoma in oral, maxillofacial
      and cervical regions.

PMID- 15562653
TI  - [Short-term follow-up study of Cercon all-ceramic crowns and bridges].
AB  - OBJECTIVE: Cercon all-ceramic system was applied clinically for the first time to
      make all-ceramic crowns and bridges for the patients. The objective of this study
      was to evaluate the short-term follow-up results of this new system from both
      technical and clinical aspects. METHODS: 15 units of Cercon all-ceramic crowns
      and bridges were fabricated and applied to 5 patients, all the cases were
      followed at 1, 3, 6 and 12 months' periods after cementation of the restorations.
      RESULTS: Cercon all-ceramic system demonstrate natural and esthetical appearance.
      No fracture, broken and color change were found. CONCLUSION: The reliability of
      all-ceramic crowns and bridges made from Cercon system was greatly improved due
      to the strengthening effects of the zirconia copings and substructures, and the
      indication of this system can be extended to long span posterior bridges. In
      addition, the better esthetics compared to PFM technique makes it a comparatively
      ideal all-ceramic system for crowns and bridges.

PMID- 15562654
TI  - [Comparison of fracture resistance of pulpless teeth restored with fiber
      reinforced composite posts and three kinds of resin core material].
AB  - OBJECTIVE: To compare the fracture resistances of pulpless teeth restored with
      FRC (Fiber Reinforced Composite) posts and three kinds of resin core material.
      METHODS: A total of 42 recently extracted upper incisors were randomly divided
      into 3 groups. Group A was restored with prefabricated glass-fiber posts and
      Artglass polymer core; group B with prefabricated glass-fiber posts and Charisma
      composite resin core; and group C with prefabricated glass-fiber posts and AB
      composite resin core. In every group, the core material was processed by hot
      press and non hot-press respectively. The posts size and shape were identical in
      the 3 groups. All teeth were fully covered with polycarbonate resin crowns.
      Fracture resistance was measured by applying point force at 130 degrees to the
      long axis of the teeth on an universal testing machine. RESULTS: Mean fracture
      threshold was 505.4 N +/- 42.0 N and 564.1 N +/- 41.7 N in group A, 411.3 N +/-
      23.3 N and 315.3 N +/- 19.1 N in group B and 358.4 N +/- 36.1 N and 423.4 N +/-
      47.5 N in group C. In all groups, there was no posts fracture and polycarbonate
      resin crowns fragmentation. CONCLUSION: The composite restoration of FRC posts
      combined with resin core and resin crown can improve the fracture resistance of
      the pulpless roots. The strength of resin core material can be increased by hot
      press methods.

PMID- 15562655
TI  - [Treatment effects with expansion and multiloop edgewise arch wire technique on
      skeletal class III malocclusion with mandibular deviation].
AB  - OBJECTIVE: The purpose of this study is to evaluate the methods of treatment on
      Class III malocclusion with mandibular deviations, and clarify the principles of
      expansion and multiloop edgewise arch wire technique. METHODS: 8 skeletal class
      III with mandibular deviations patients were selected (male 3, female 5, aged 12
      18). They were all corrected with maxillary expansion and multiloop edgewise arch
      wire technique. RESULTS: In all cases, molar relationships were class I, the
      overbite and the overjet were normal, and the upper and lower midline were
      harmony. CONCLUSION: Mild and moderate skeletal class III with mandibular
      deviation can be corrected successfully by maxillary expansion and multiloop
      edgewise arch wire technique.

PMID- 15562656
TI  - [Changes of cranio-facial hard tissue after orthodontic treatment in bimaxillary
      protrusive patients].
AB  - OBJECTIVE: The aim of this study is to investigate the changes of hard tissue
      profile in anterior-posterior and vertical direction in bimaxillary protrusion
      patients after orthodontic treatment. METHODS: A total of 24 bimaxillary
      protrusion patients (male 8, female 16), aged from 11.2 to 29.0 (average 16.9
      years old), were selected to be treated with standard edgewise technique
      consisted of 4 first premolars extraction. Cephalometrics were taken before and
      after treatment. The changes of hard tissue profile were studied using the
      computer-aid X-ray cephalometric analysis. RESULTS: 1. The length of the
      maxillary and the mandible increased significantly, but the anterior-posterior
      relationship of the maxillary and the mandible did not change significantly. 2.
      The anterior and posterior facial height increased significantly, but the ratio
      of anterior and posterior facial height and the angle of MP-FH which reflected
      the inclination of the mandible plane did not change significantly. 3. The height
      of the upper and lower first molar increased significantly along with the
      increase of the anterior and posterior facial height. 4. The height of the upper
      incisors increased significantly, but the height of the lower incisors decreased
      significantly. CONCLUSION: The anchorage in anterior-posterior and vertical
      direction were controlled preferably, the patients did not manifest
      disadvantageous vertical growth trend.

PMID- 15562657
TI  - [Using moire interferometre in the study of porcelain-fused-metal interfacial
      fracture mechanics].
AB  - OBJECTIVE: To evaluate the usage of moire interferometre in porcelain-fused-metal
      interfacial fracture mechanics. METHODS: Raster was produced on the surface of
      samples with different thickness of porcelain and metal in 5 groups. The stripes
      of u field and v field under different load were collected. Then the rupture
      tenacity Jc was calculated and the extensions of flaws were observed. RESULTS:
      Stress concentration appeared around the flaws under load conditions. The stripe
      became denser under more load. The rupture tenacity Jc and the direction of flaw
      extension of each group were different. CONCLUSION: Moire interferometre can be
      used in the study of porcelain-fused-metal interfacial fracture mechanics and to
      prognosticate the direction of flaw extension.

PMID- 15562658
TI  - [Investigation on the association of interleukin-1 genotype polymorphism with
      chronic periodontitis].
AB  - OBJECTIVE: To examine the distribution of IL-1 genotypes among the people with
      Han nationality of different periodontal health status and to evaluate if there
      is an association between the genotype of IL-1 and the severity of periodontitis.
      METHODS: 271 subjects of Han nationality were selected, among them there were 182
      cases of chronic periodontitis and 89 subjects of periodontal healthy control.
      Full periodontal examinations were taken including full-mouth clinical attachment
      loss measurements, probing depths and bleeding on probing. DNA samples were
      obtained with buccal swabbing technique and were further analyzed for IL-1
      genotype polymorphisms using PCR-RFLP-based method. RESULTS: The results showed a
      significant increase in the frequency of IL-1A-889/Nco I allele 2, IL-1B +
      3953/Taq I allele 2, IL-1B-511/Ava I allele 2, IL-1A-889 plus IL-1B-511 allele 2
      and IL-1B + 3953 plus IL-1B-511 allele 2 in patients with severe chronic
      periodontitis as compared with periodontally healthy controls. CONCLUSION:
      Findings from this study bring into question the usefulness of the genotypes of
      allele 2 of IL-1A-889, IL-1B-511 and IL-1B + 3953 as a method for determining the
      susceptibility of Chinese patients to chronic periodontitis. There is a possible
      role of IL-1 gene polymorphisms in the susceptibility to chronic periodontitis
      for some patients.

PMID- 15562659
TI  - [Recombinant human bone morphogenetic protein-2 transform NIH3T3 fibroblast to
      osteo-like cells].
AB  - OBJECTIVE: To examine the effect of recombinant human bone morphogenetic protein
      2 (rhBMP-2) on NIH3T3 cells. METHODS: The NIH3T3 cells were cultured in DMEM with
      50 microg/L rhBMP-2. The proliferation ability, alkaline phosphatase (ALP)
      activity and osteocalcin (OC) quantity of NIH3T3 cells were investigated.
      RESULTS: The cells showed decreased proliferation ability but enhanced ALP
      activity and OC quantity. CONCLUSION: 50 microg/L rhBMP-2 can transform NIH3T3
      fibroblasts to osteo-like cells.

PMID- 15562660
TI  - [Typing human papilloma virus (HPV) infection in the warts of oral mucosa from
      HIV-positive patients].
AB  - OBJECTIVE: To detect and type human papilloma virus (HPV) in the warts of oral
      mucosa from HIV-positive patients, and better understand the biological
      characters of these oral warts. METHODS: Polymerase chain reaction (PCR) was used
      to detect and type HPV infection by consensus HPV primers Gp5+/Gp6+ and specific
      HPV primers (HPV6/11, 16, 18, 31, 33) in 34 cases of oral mucosa warts from HIV
      positive patients. RESULTS: The HPV infection rate was 88.2% by consensus HPV
      primers Gp5+/Gp6+; the HPV infection rate of HPV6/11, 16, 18, 31 was respectively
      47.06%, 11.67%; 2.94%, and 5.88% by specific HPV primers. CONCLUSION: Most
      lesions of oral warts from HIV-positive patients are associated with the
      infection of HPV. The low risk HPV6/11 infection is more common than the high
      risk HPV16, 18, 31.

PMID- 15562661
TI  - [Relationship between condylar marrow signal abnormalities and temporomandibular
      joint internal derangement].
AB  - OBJECTIVE: To investigate the relationship between condylar marrow signal
      abnormalities and temporomandibular joint internal derangement (TMJID). METHODS:
      Oblique sagittal T1 weighted MR imaging at closed and open mouth and Oblique
      sagittal T2 weighted MR imaging at closed mouth were obtained from 88 joints of
      44 patients suffering from TMD. Condylar marrow signal abnormalities were
      reviewed and classified into bone marrow edema pattern (hypointense T1,
      hyperintense T2), sclerosis pattern (hypointense T1 and hypointense T2) and
      combined edema and sclerosis pattern. RESULTS: Of 88 joints, 13 (14.8%) joints
      showed condylar marrow signal abnomalities, among which 11 belonged to edema
      pattern and, 1 was sclerosis pattern and the other was the combined patten. Of 13
      joints with condylar marrow signal abnomalities, 11 (84.6%) had TMJID. Of 75
      joints with normal marrow signal, 25 (33.3%) joints had TMJID. There was
      significant correlation between condylar marrow signal abnormalities and TMJID (P
      < 0.05). CONCLUSION: Disc displacement is one of the factors inducing condylar
      marrow signal abnormalities. The pathological process from disc displacement to
      osteonecrosis requires further study.

PMID- 15562662
TI  - [Experimental study on guiding bone regeneration with bovine pericardium
      membrane].
AB  - OBJECTIVE: To explore the feasibility of bovine pericardium used as a material
      for guiding bone regeneration. METHODS: 1 cm x 1 cm x 0.5 cm defects were created
      on both buccal sides of the mandibles of 11 dogs. One side was covered with
      Glutaraldehyde (GA) cross-linking bovine pericardium; no membrane covered side
      was used as control. The animals were sacrificed in 2 weeks, 4 weeks, 8 weeks and
      16 weeks after operation to observe the repair of the bone defects. RESULTS: (1)
      Wounds healed well in 10 dogs. Meanwhile, wounds in dogs of 16 weeks group healed
      badly and severe inflammatory response was found in bovine pericardium treated
      area. (2) The pericardium can be maintained in vivo for 16 weeks without
      absorption, there were only mild inflammatory cells invading. (3) The bone
      defects covered with bovine pericardium repaired better than control groups
      significantly. CONCLUSION: (1) GA bovine pericardium have the effect on guiding
      bone regeneration in the repair of dog experimental bone defects and it is
      possible that the bovine pericardium will be used as a new kind of GBR material;
      (2) GA bovine pericardium has good biocompatibility.

PMID- 15562663
TI  - [Experimental study on the microcosmic changes of compressed premaxillary suture
      with laser scanning confocal microscopy].
AB  - OBJECTIVE: The aim of this experiment is to know whether active orthopedic
      appliance is rationale to do presurgical treatment and seek some regularities.
      METHODS: Laser scanning confocal microscopy and triple fluorochrome labeling in
      bone were used to observe and study detailed changes occurred in compressed
      suture systematically. RESULTS: Widened suture and broken fibres between the
      adjoining bones was observed at the 3rd week postoperatively. At the 3rd week
      hyperplasia of organic tissue components was also seen. At the 6 and 9th week
      there were no apparent differences among all groups no matter whether in control
      group or experimental groups. CONCLUSION: Retarding injury of compressed suture
      and surrounding tissue hyperplasia exists. With growth and development wounded
      suture will gradually assimilate to control group structurally and functionally.

PMID- 15562664
TI  - Pathophysiology of portal hypertension.
AB  - Portal hypertension is a common clinical syndrome associated with chronic liver
      diseases, and is characterized by a pathological increase in portal pressure that
      leads to the formation of portosystemic collaterals resulting in shunting of
      portal blood into the systemic circulation. The increase in portal pressure is
      due to an increase in vascular resistance and an elevated portal blood flow. The
      site of increased resistance is variable, and dependent upon the disease process.
      The site of relative obstruction may be prehepatic, hepatic, or posthepatic.
      There are several intrahepatic lesions that lead to increased resistance. Some of
      these lesions are irreversible, like fibrosis, regenerating nodules, and
      capillarization of the space of Disse; however, there is a functional component,
      increased vascular tone, which contributes to increased intrahepatic resistance
      and is potentially reversible. Another important factor contributing to the
      increased portal pressure is elevated portal blood flow. Peripheral
      vasodilatation initiates the classical profile of decreased systemic resistance,
      expanded plasma volume, elevated splanchnic blood flow, and elevated cardiac
      index, which characterize the hyperdynamic circulatory state. This hyperdynamic
      circulation is responsible for various complications of portal hypertension.

PMID- 15562665
TI  - New concepts in the pathogenesis of portal hypertension: hepatic wounding and
      stellate cell contractility.
AB  - The pathogenesis of portal hypertension is multifactorial, and appears to result
      from interplay between fixed and dynamically modulable elements; the stellate
      cell is a newly recognized example of the latter. This perisinusoidal, pericyte
      like cell has contractile features that are most prominent after liver injury,
      concomitant with their activation. These data imply an exaggerated contractile
      phenotype in the cirrhotic liver. This cell may contribute to increased
      intrahepatic portal hypertension via perisinusoidal constriction of the sinusoid
      or by contraction of fibrous extracellular matrix rich in type I collagen with
      concomitant disruption of lobular architecture. Endothelins and NO play a major
      role in the modulation of stellate cell contractility, and are therefore
      important in the pathogenesis of intrahepatic portal hypertension. These new data
      provide potential areas for therapeutic intervention in this clinical entity.

PMID- 15562666
TI  - Natural history of portal hypertension.
AB  - A rise in pressure in the portal vein is a frequent occurrence in patients with
      cirrhosis. One common manifestation affecting at least 50% of cirrhosis patients
      is the development of gastroesophageal varices and portal hypertensive
      gastropathy. Bleeding from gastric or esophageal varices will occur in
      approximately 1/4 of cirrhotic patients with an associated high mortality. Large
      esophageal varices that have red color signs and isolated gastric varices in the
      fundus of the stomach are most likely to hemorrhage. The greatest risk of
      bleeding is during the first year following the index endoscopy. Once varices
      have bled they are almost certain to rebleed in the absence of therapy.
      Similarly, severe portal hypertensive gastropathy is likely to cause chronic
      blood loss. Knowledge of the natural history of gastroesophageal varices allows
      for the development of effective treatment strategies.

PMID- 15562667
TI  - Cost assessments in the management of variceal bleeding.
AB  - This article defines and reviews the methods for economic cost assessments in the
      management of variceal hemorrhage. It also presents and discusses the results of
      cost-benefit, cost-effectiveness, and cost assessment studies on the management
      of variceal hemorrhage and proposes future directions for additional studies.

PMID- 15562668
TI  - Pharmacologic therapy of portal hypertension and variceal hemorrhage.
AB  - Patients with large esophageal varices who are deemed compliant and have no
      contraindications to beta-blocker therapy should be started on nonselective beta
      adrenergic blockers (Fig. 5). The dose should be titrated to a 25% decrease in
      resting heart rate, a resting heart rate of 55 to 60 beats per minute, or
      development of symptoms, in which case the dose should be decreased until the
      patient's symptoms abate. If available, measurements of the HVPG at baseline and
      3 months can be very helpful in ascertaining the response to treatment and in
      making the appropriate adjustments (e.g., adding a second drug). Sclerotherapy or
      endoscopic variceal ligation are the preferred therapies for treatment of acute
      esophageal variceal bleeding. Concomitant use of vasoactive drugs can supplement
      endoscopic treatment. They offer the advantage of early administration as soon as
      the diagnosis is suspected while awaiting endoscopy. Unlike endoscopic treatment,
      they decrease portal pressure and are the only established treatment for
      nonvariceal sources of bleeding related to portal hypertension. Once the index
      bleed is controlled, the patient should be started on treatment to reduce the
      high risk of recurrent variceal hemorrhage (Fig. 6). For patients with well
      compensated cirrhosis, pharmacologic therapy may be desirable. For less compliant
      patients or patients with decompensated cirrhosis, an endoscopic technique, such
      as variceal ligation, may be preferable. Combinations of pharmacologic agents or
      pharmacologic agents and endoscopic procedures may offer hope for better control,
      but their efficacy needs to be demonstrated in RCTs. For patients who rebleed
      despite maximal pharmacologic or endoscopic therapy, a TIPS procedure, surgically
      created shunt, or liver transplantation should be considered, with the decision
      based on the patient's condition and the local availability of these options.

PMID- 15562669
TI  - Sclerotherapy versus banding in the treatment of variceal bleeding.
AB  - Endoscopic sclerotherapy has been the mainstay in the management of esophageal
      variceal bleeding to control acute bleeding and decrease recurrent bleeding.
      Endoscopic variceal ligation is a new technique that is equally effective in the
      control of acute bleeding but achieves obliteration of varices in fewer treatment
      sessions with presumably less cost, results in a lower rebleeding rate, has fewer
      complications, and is associated with reduced mortality. Combination therapy with
      both endoscopic variceal ligation and endoscopic sclerotherapy appears to have no
      clear advantage over variceal ligation alone. On the basis of the results of a
      number of trials comparing sclerotherapy with band ligation, endoscopic variceal
      ligation has evolved to be the preferred first line modality for the endoscopic
      treatment of variceal bleeding.

PMID- 15562670
TI  - The role of the transjugular intrahepatic portal-systemic shunt in the management
      of variceal bleeding.
AB  - For patients who present with variceal bleeding refractory to endoscopic and
      pharmacologic methods, TIPS is a new and effective therapy. Stents are used in
      selected patients with decompensated liver disease and those who anticipate liver
      transplantation within 6 to 12 months. Surveillance of TIPS with ultrasound, with
      or without venography, is recommended to diagnose and treat stenosis or occlusion
      before variceal hemorrhage recurs. Hepatic encephalopathy may develop in a subset
      of patients, but it is usually well controlled with conservative measures. Child
      Pugh and APACHE scores are predictive of patient survival after TIPS. Randomized
      controlled trials will be necessary to assess whether TIPS is useful, safe, and
      cost effective for the management of variceal bleeding in patients with end stage
      liver disease.

PMID- 15562671
TI  - The role of surgery in the treatment of portal hypertension.
AB  - The role of surgery in the treatment of portal hypertension continues to evolve.
      Pharmacologic and endoscopic therapies are the primary treatment modalities for
      the prophylaxis and treatment of variceal bleeding and ascites. Failure of these
      therapies is the indication for invasive intervention such as TIPS, surgical
      shunt, or devascularization. Distal splenoreal shunting provides selective
      variceal decompression with less encephalopathy and accelerated hepatic failure
      than portal decompression. Liver transplantation remains the treatment of choice
      for patients with poor hepatic function.

PMID- 15562672
TI  - The role of liver transplantation in the management of portal hypertension.
AB  - Liver transplantation is the treatment of choice for end stage liver disease and
      not a treatment specifically for portal hypertension. A patient with
      complications of portal hypertension must be evaluated for the presence,
      etiology, and severity of liver disease to determine the most appropriate
      therapy. In a Child's Class A patient, who would not be a liver transplant
      candidate for two to three years, surgical shunts may be indicated. Shunt
      surgery, however, does not address the underlying liver disease. Liver
      transplantation is reserved for the patient with complications of cirrhosis (such
      as ascites, encephalopathy, malnutrition, intractable pruritus, and variceal
      hemorrhage) for whom no other form of therapy exists.

PMID- 15562673
TI  - A commonsense approach to variceal bleeding.
AB  - A cirrhotic patient with large varices and red color signs at endoscopy, and a
      portal pressure greater than 12 mmHg, has a high risk of bleeding from those
      varices in the near future. Prophylactic therapy with a nonselective beta
      adrenergic blocking drug or long acting nitroglycerin reduces the risk of
      developing the first bleed and increases life expectancy. The acute variceal
      bleed requires prompt resuscitation with volume replacement, early initiation of
      vasoactive drugs (octreotide, somatosatin, or vasopressin plus nitroglycerin) to
      reduce portal pressure and decrease splanchnic flow, and early diagnostic
      endoscopy to determine the cause of bleeding. Variceal banding or sclerotherapy
      is successful in controlling the acute bleed in up to 90% of cases. Beta
      adrenergic blocker therapy should be instituted once the bleed has been
      controlled and banding/sclerotherapy continued until the varices have been
      obliterated. In the patient with recalcitrant or recurrent bleeding, TIPS,
      selective shunt surgery, or liver transplantation may be options depending on the
      specifics of the particular case.

PMID- 15562674
TI  - Pathophysiology, complications, and treatment of ascites.
AB  - In the past few years, there have been important advances in the field of
      pathogenesis and management of ascites and spontaneous bacterial peritonitis in
      cirrhosis. A new pathogenic theory of ascites and renal dysfunction in cirrhosis
      has been presented, and previously ill-defined conditions, such as refractory
      ascites and hepatorenal syndrome, have been defined precisely. The reintroduction
      of therapeutic paracentesis has modified markedly the way in which patients
      hospitalized for ascites are treated. The use of potent and safe antibiotics has
      improved the resolution rate and survival of patients with spontaneous bacterial
      peritonitis, and the use of oral antibiotics will simplify the management of this
      condition in the near future. Finally, prophylactic antibiotic regimens represent
      a major step forward in the prevention of spontaneous bacterial peritonitis in
      subsets of cirrhotic patients with a great risk of developing this complication.

PMID- 15562675
TI  - Portal systemic encephalopathy.
AB  - The goal of this article is to update the status of Portal systemic
      encephalopathy (PSE) in the light of new data. First, PSE is the context of other
      types of hepatic encephalopathy. Subsequently, current views of the pathogenesis
      of the disorder are discussed, followed by an analysis of therapeutic options.
      Diagnosis will not be considered, as no major new developments have recently been
      documented in this area.

PMID- 15562676
TI  - The hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrome occurs in subjects with chronic liver disease and/or
      portal hypertension who develop intrapulmonary vasodilation resulting in arterial
      deoxygenation. Clinical and basic science studies investigating the
      pathophysiology of HPS are presented. A diagnostic algorithm is provided using
      contrast echocardiography, the lung perfusion scan, and pulmonary angiography.
      Medical therapy and experience with liver transplantation are reviewed.

PMID- 15562677
TI  - Portal hypertension in children.
AB  - This chapter reviews the common causes of portal hypertension in children. It
      specifies how the treatment strategy for portal hypertension in patients without
      significant hepatic dysfunction differs from the management of children with
      cirrhosis. It describes the application of newer treatment modalities such as
      TIPS and partial splenic embolization in children and reviews the current
      recommendations for surgical intervention in these patients.

PMID- 15562678
TI  - Noncirrhotic portal hypertension.
AB  - This article reviews the different conditions leading to noncirrhotic
      intrahepatic portal hypertension, describes the related vascular lesions, and
      provides a review of the clinical characteristics, diagnosis, and treatment
      options available. Diseases associated with noncirrhotic portal hypertension are
      also specifically discussed.

PMID- 15562679
TI  - Effects of genetic drift on variance components under a general model of
      epistasis.
AB  - We analyze the changes in the mean and variance components of a quantitative
      trait caused by changes in allele frequencies, concentrating on the effects of
      genetic drift. We use a general representation of epistasis and dominance that
      allows an arbitrary relation between genotype and phenotype for any number of
      diallelic loci. We assume initial and final Hardy-Weinberg and linkage
      equilibrium in our analyses of drift-induced changes. Random drift generates
      transient linkage disequilibria that cause correlations between allele frequency
      fluctuations at different loci. However, we show that these have negligible
      effects, at least for interactions among small numbers of loci. Our analyses are
      based on diffusion approximations that summarize the effects of drift in terms of
      F, the inbreeding coefficient, interpreted as the expected proportional decrease
      in heterozygosity at each locus. For haploids, the variance of the trait mean
      after a population bottleneck is var(delta(z)) = sigma(n)k=1 FkV(A(k)), where n
      is the number of loci contributing to the trait variance, V(A(1)) = V(A) is the
      additive genetic variance, and V(A(k)) is the kth-order additive epistatic
      variance. The expected additive genetic variance after the bottleneck, denoted
      (V*(A)), is closely related to var(delta(z)); (V*(A)) = (1 - F) sigma(n)k=1 kFk
      1V(A(k)). Thus, epistasis inflates the expected additive variance above V(A)(1 -
      F), the expectation under additivity. For haploids (and diploids without
      dominance), the expected value of every variance component is inflated by the
      existence of higher order interactions (e.g., third-order epistasis inflates
      (V*(AA. This is not true in general with diploidy, because dominance alone can
      reduce (V*(A)) below V(A)(1 - F) (e.g., when dominant alleles are rare). Without
      dominance, diploidy produces simple expressions: var(delta(z)) = sigma(n)k=1
      (2F)kV(A(k)) and (V(A)) = (1 - F) sigma(n)k=1 k(2F)k-1V(A(k)). With dominance
      (and even without epistasis), var(delta(z)) and (V*(A)) no longer depend solely
      on the variance components in the base population. For small F, the expected
      additive variance simplifies to (V*(A)) approximately equal to (1 - F)V(A) +
      4FV(AA) + 2FV(D) + 2FC(AD), where C(AD) is a sum of two terms describing
      covariances between additive effects and dominance and additive X dominance
      interactions. Whether population bottlenecks lead to expected increases in
      additive variance depends primarily on the ratio of nonadditive to additive
      genetic variance in the base population, but dominance precludes simple
      predictions based solely on variance components. We illustrate these results
      using a model in which genotypic values are drawn at random, allowing extreme and
      erratic epistatic interactions. Although our analyses clarify the conditions
      under which drift is expected to increase V(A), we question the evolutionary
      importance of such increases.

PMID- 15562680
TI  - Comparing strengths of directional selection: how strong is strong?
AB  - The fundamental equation in evolutionary quantitative genetics, the Lande
      equation, describes the response to directional selection as a product of the
      additive genetic variance and the selection gradient of trait value on relative
      fitness. Comparisons of both genetic variances and selection gradients across
      traits or populations require standardization, as both are scale dependent. The
      Lande equation can be standardized in two ways. Standardizing by the variance of
      the selected trait yields the response in units of standard deviation as the
      product of the heritability and the variance-standardized selection gradient.
      This standardization conflates selection and variation because the phenotypic
      variance is a function of the genetic variance. Alternatively, one can
      standardize the Lande equation using the trait mean, yielding the proportional
      response to selection as the product of the squared coefficient of additive
      genetic variance and the mean-standardized selection gradient. Mean-standardized
      selection gradients are particularly useful for summarizing the strength of
      selection because the mean-standardized gradient for fitness itself is one, a
      convenient benchmark for strong selection. We review published estimates of
      directional selection in natural populations using mean-standardized selection
      gradients. Only 38 published studies provided all the necessary information for
      calculation of mean-standardized gradients. The median absolute value of
      multivariate mean-standardized gradients shows that selection is on average 54%
      as strong as selection on fitness. Correcting for the upward bias introduced by
      taking absolute values lowers the median to 31%, still very strong selection.
      Such large estimates clearly cannot be representative of selection on all traits.
      Some possible sources of overestimation of the strength of selection include
      confounding environmental and genotypic effects on fitness, the use of fitness
      components as proxies for fitness, and biases in publication or choice of traits
      to study.

PMID- 15562681
TI  - Habitat selection, acoustic adaptation, and the evolution of reproductive
      isolation.
AB  - We examined barriers to gene flow in a hybrid zone of two subspecies of the song
      sparrow (Melospiza melodia). We focused on how mating signals and mate choice
      changed along an environmental gradient and gathered data on the morphology,
      genetics, ecology, and behavior across the zone. Melospiza m. heermanni of the
      Pacific slope of California and M. m. fallax of the Sonoran Desert, each distinct
      in plumage, meet across a steep environmental gradient in southeastern
      California. Although both subspecies occur in riparian habitat, their occupied
      habitat differs structurally, the former subspecies occurring in areas with
      denser understory and greater vertical heterogeneity. Song elements varied
      concomitantly, as predicted by the acoustic adaptation hypothesis, with heermanni
      having lower-pitched, more widely spaced elements. Females of both subspecies
      responded more strongly to homotypic than heterotypic song, and addition of
      subspecific plumage cues increased response if song was homotypic but not if
      heterotypic. Females thus assess multiple male traits, weighing song more
      heavily. Males of both subspecies showed significantly greater agonistic response
      to homotypic song. Microsatellite variation is correlated significantly with
      plumage variation across the zone and suggests limited gene flow between the
      taxa. The association of song and plumage with the environment and in turn with
      assortative mating suggests a means by which reproductive isolation may evolve or
      be maintained in hybrid zones.

PMID- 15562682
TI  - Evolution of Wolbachia cytoplasmic incompatibility types.
AB  - The success of obligate endosymbiotic Wolbachia infections in insects is due in
      part to cytoplasmic incompatibility (CI), whereby Wolbachia bacteria manipulate
      host reproduction to promote their invasion and persistence within insect
      populations. The observed diversity of CI types raises the question of what the
      evolutionary pathways are by which a new CI type can evolve from an ancestral
      type. Prior evolutionary models assume that Wolbachia exists within a host
      individual as a clonal infection. While endosymbiotic theory predicts a general
      trend toward clonality, Wolbachia provides an exception in which there is
      selection to maintain diversity. Here, evolutionary trajectories are discussed
      that assume that a novel Wolbachia variant will co-exist with the original
      infection type within a host individual as a superinfection. Relative to prior
      models, this assumption relaxes requirements and allows additional pathways for
      the evolution of novel CI types. In addition to describing changes in the
      Wolbachia infection frequency associated with the hypothesized evolutionary
      events, the predicted impact of novel CI variants on the host population is also
      described. This impact, resulting from discordant evolutionary interests of
      symbiont and host, is discussed as a possible cause of Wolbachia loss from the
      host population or host population extinction. The latter is also discussed as
      the basis for an applied strategy for the suppression of insect pest populations.
      Model predictions are discussed relative to a recently published Wolbachia genome
      sequence and prior characterization of CI in naturally and artificially infected
      insects.

PMID- 15562683
TI  - Intra-individual coexistence of a Wolbachia strain required for host oogenesis
      with two strains inducing cytoplasmic incompatibility in the wasp Asobara tabida.
AB  - Cytoplasmically inherited symbiotic Wolbachia bacteria are known to induce a
      diversity of phenotypes on their numerous arthropod hosts including cytoplasmic
      incompatibility, male-killing, thelytokous parthenogenesis, and feminization. In
      the wasp Asobara tabida (Braconidae), in which all individuals harbor three
      genotypic Wolbachia strains (wAtab1, wAtab2 and wAtab3), the presence of
      Wolbachia is required for insect oogenesis. To elucidate the phenotype of each
      Wolbachia strain on host reproduction, especially on oogenesis, we established
      lines of A. tabida harboring different combinations of these three bacterial
      strains. We found that wAtab3 is essential for wasp oogenesis, whereas the two
      other strains, wAtabl and wAtab2, seem incapable to act on this function.
      Furthermore, interline crosses showed that strains wAtab1 and wAtab2 induce
      partial (about 78%) cytoplasmic incompatibility of the female mortality type.
      These results support the idea that bacterial genotype is a major factor
      determining the phenotype induced by Wolbachia on A. tabida hosts. We discuss the
      implications of these findings for current hypotheses regarding the evolutionary
      mechanisms by which females of A. tabida have become dependent on Wolbachia for
      oogenesis.

PMID- 15562684
TI  - Speciation in Hawaiian angiosperm lineages: cause, consequence, and mode.
AB  - The biota of Hawaiian Islands is derived entirely from long distance dispersal,
      often followed by in situ speciation. Species descended from each colonist
      constitute monophyletic lineages that have diverged to varying degrees under
      similar spatial and temporal constraints. We partitioned the Hawaiian angiosperm
      flora into lineages and assessed morphological, ecological, and biogeographic
      characteristics to examine their relationships to variation in species number
      (S). Lineages with external bird dispersal (through adhesion) were significantly
      more species-rich than those with abiotic dispersal, but only weakly more species
      rich than lineages with internal bird dispersal (involving fleshy fruits).
      Pollination mode and growth form (woody vs. herbaceous) had no significant effect
      on S, in contrast to studies of angiosperm families. S relates positively to the
      geographic and ecological range size of whole lineages, but negatively to local
      abundance and mean range sizes of constituent species. Species-rich lineages
      represent a large proportion of major adaptive shifts, although this appears to
      be an artifact of having more species. Examination of 52 sister species pairs in
      numerous lineages provides evidence for allopatric (including peripheral
      isolates) and parapatric (ecological) modes, with 15 cases of each. Although
      postspeciational dispersal may obscure these modes in many of the remaining
      cases, instances of sympatric and hybrid speciation are also discussed. Because
      speciation is both a consequence and a cause of ecological and biogeographic
      traits, speciation mode may be integral to relationships between traits. We
      discuss the role of speciation in shaping the regional species pool.

PMID- 15562685
TI  - Cospeciation analysis of an obligate pollination mutualism: have Glochidion trees
      (Euphorbiaceae) and pollinating Epicephala moths (Gracillariidae) diversified in
      parallel?
AB  - Species-specific obligate pollination mutualism between Glochidion trees
      (Euphorbiaceae) and Epicephala moths (Gracillariidae) involves a large number of
      interacting species and resembles the classically known fig-fig wasp and yucca
      yucca moth associations. To assess the extent of parallel cladogenesis in
      Glochidion-Epicephala association, we reconstruct phylogenetic relationships of
      18 species of Glochidion using nuclear ribosomal DNA sequences (internal and
      external transcribed spacers) and those of the corresponding 18 Epicephala
      species using mitochondrial (the cytochrome oxidase subunit I gene) and nuclear
      DNA sequences (the arginine kinase and elongation factor-1alpha genes). Based on
      the obtained phylogenies, we determine whether Glochidion and Epicephala have
      undergone parallel diversification using several different methods for
      investigating the level of cospeciation between phylogenies. These tests indicate
      that there is generally a greater degree of correlation between Glochidion and
      Epicephala phylogenies than expected in a random association, but the results are
      sensitive to selection of different phylogenetic hypotheses and analytical
      methods for evaluating cospeciation. Perfect congruence between phylogenies is
      not found in this association, which likely resulted from host shift by the
      moths. The observed significant discrepancy between Glochidion and Epicephala
      phylogenies implies that the one-to-one specificity between the plants and moths
      has been maintained through a complex speciation process or that there is an
      underestimated diversity of association between Glochidion trees and Epicephala
      moths.

PMID- 15562686
TI  - Multiple origin of viviparity in Southeast Asian gastropods (Cerithioidea:
      Pachychilidae) and its evolutionary implications.
AB  - This study aims at a better understanding of the evolutionary significance of
      viviparity in some freshwater gastropods. We use a phylogeny based on partial
      sequences of the mitochondrial 16S gene of representatives of the limnetic and
      pantropical Pachychilidae to infer the relationships within this particular group
      of cerithioideans and the evolution of reproductive strategies. The phylogeny
      presented herein implies a new systematization and suggests that viviparity has
      appeared three times among the Pachychilidae. This is supported by the finding of
      very distinct reproductive morphologies in different lineages of viviparous taxa
      that are exclusively found in Southeast Asia. Based on the observation that
      oviparity is the ancestral character state in this freshwater family, we conclude
      that viviparity has evolved subsequent to the exploration of freshwater. We
      present data showing that all Pachychilidae produce considerably larger but fewer
      egg capsules compared to most marine snails. In other studies on freshwater
      gastropods, this has been discussed as an adaptation to freshwater environments.
      In this context we hypothesize that the increased parental investment involved in
      the enlargement of eggs in concert with the reduction of clutch sizes was the
      driving factor that ultimately lead to the evolution of viviparity in the Asian
      taxa. Consequently, although not directly correlated with the colonization of the
      new adaptive zone, viviparity is strongly favored by other consequences of this
      step. Hence, we hypothesize that the production of large eggs, which is
      necessitated by the exploration of freshwater, represents a preadaptation
      existing in those ancestors from which viviparous pachychilid lineages eventually
      evolved in Southeast Asia.

PMID- 15562687
TI  - Speciation and diversity on tropical rocky shores: a global phylogeny of snails
      of the genus Echinolittorina.
AB  - A phylogenetic approach to the origin and maintenance of species diversity
      ideally requires the sampling of all species within a clade, confirmation that
      they are evolutionarily distinct entities, and knowledge of their geographical
      distributions. In the marine tropics such studies have mostly been of fish and
      reef-associated organisms, usually with high dispersal. In contrast, snails of
      the genus Echinolittorina (Littorinidae) are restricted to rocky shores, have a
      four-week pelagic development (and recorded dispersal up to 1400 km), and show
      different evolutionary patterns. We present a complete molecular phylogeny of
      Echinolittorina, derived from Bayesian analysis of sequences from nuclear 28S
      rRNA and mitochondrial 12S rRNA and COI genes (nodal support indicated by
      posterior probabilities, maximum likelihood, and neighbor-joining bootstrap).
      This consists of 59 evolutionarily significant units (ESUs), including all 50
      known taxonomic species. The 26 ESUs found in the Indo-West Pacific region form a
      single clade, whereas the eastern Pacific and Atlantic species are basal. The
      earliest fossil occurred in the Tethys during the middle Eocene and we suggest
      that the Indo-West Pacific clade has been isolated since closure of the Tethyan
      seaway in the early Miocene. The geographical distributions of all species (based
      on more than 3700 locality records) appear to be circumscribed by barriers of low
      temperature, unsuitable sedimentary habitat, stretches of open water exceeding
      about 1400 km, and differences in oceanographic conditions on the continuum
      between oceanic and continental. The geographical ranges of sister species show
      little or no overlap, indicating that the speciation mode is predominantly
      allopatric. Furthermore, range expansion following speciation appears to have
      been limited, because a high degree of allopatry is maintained through three to
      five branching points of the phylogeny. This may be explained by infrequent long
      distance colonization, habitat specialization on the oceanic/continental
      gradient, and perhaps by interspecific competition. In the eastern Pacific plus
      Atlantic we identify five cases of divergence on either side of the Isthmus of
      Panama, but our estimates of their ages pre-date the emergence of the Isthmus.
      There are three examples of sister relationships between species in the western
      Atlantic and eastern Atlantic, all resulting from dispersal to the east. Within
      the Indo-West Pacific, we find no geographical pattern of speciation events;
      narrowly endemic species of recent origin are present in both peripheral and
      central parts of the region. Evidence from estimated divergence times of sister
      species, and from a plot of the number of lineages over time, suggest that there
      has been no acceleration of diversification during the glacio-eustatic cycles of
      the Plio-Pleistocene. In comparison with reefal organisms, species of
      Echinolittorina on rocky shores may be less susceptible to extinction or
      isolation during sea-level fluctuations. The species richness of Echinolittorina
      in the classical biogeographic provinces conforms to the common pattern of
      highest diversity (11 species) in the central "East Indies Triangle" of the Indo
      West Pacific, with a subsidiary focus in the eastern Pacific and western
      Atlantic, and lowest diversity in the eastern Atlantic. The diversity focus in
      the East Indies Triangle is produced by a mosaic of restricted allopatric species
      and overlap of a few widespread ones, and is the result of habitat specialization
      rather than historical vicariance. This study emphasizes the plurality of
      biogeographic histories and speciation patterns in the marine tropics.

PMID- 15562688
TI  - Evolution of ant-cultivar specialization and cultivar switching in Apterostigma
      fungus-growing ants.
AB  - Almost all of the more than 200 species of fungus-growing ants (Formicidae:
      Attini) cultivate litter-decomposing fungi in the family Lepiotaceae
      (Basidiomycota: Agaricales). The single exception to this rule is a subgroup of
      ant species within the lower attine genus Apterostigma, which cultivate
      pterulaceous fungi distantly related to the Lepiotaceae. Comparison of cultivar
      and ant phylogenies suggests that a switch from lepiotaceous to pterulaceous
      fungiculture occurred only once in the history of the fungus-growing ants. This
      unique switch occurred after the origin of the genus Apterostigma, such that the
      basal Apterostigma lineages retained the ancestral attine condition of
      lepiotaceous fungiculture, and none of the Apterostigma lineages in the
      monophyletic group of pterulaceous fungiculturists are known to have reverted
      back to lepiotaceous fungiculture. The origin of pterulaceous fungiculture in
      attine ants may have involved a unique transition from the ancestral cultivation
      of litter-decomposing lepiotaceous fungi to the cultivation of wood-decomposing
      pterulaceous fungi. Phylogenetic analyses further indicate that distantly related
      Apterostigma ant species sometimes cultivate the same cultivar lineage,
      indicating evolutionarily frequent, and possibly ongoing, exchanges of fungal
      cultivars between Apterostigma ant species. The pterulaceous cultivars form two
      sister clades, and different Apterostigma ant lineages are invariably associated
      with, and thus specialized on, only one of the two cultivar clades. However,
      within clades Apterostigma ant species are able to switch between fungi. This
      pattern of broad specialization by attine ants on defined cultivar clades,
      coupled with flexible switching between fungi within cultivar clades, is also
      found in other attine lineages and appears to be a general phenomenon of
      fungicultural evolution in all fungus-growing ants.

PMID- 15562689
TI  - Testing the out-of-Florida hypothesis on the origin of cheating in the yucca
      yucca moth mutualism.
AB  - Mutualistic interactions can be exploited by cheaters that take the rewards
      offered by mutualists without providing services in return. The evolution of
      cheater species from mutualist ancestors is thought to be possible under
      particular ecological conditions. Here we provide a test of the first explicit
      model of the transition from mutualism to antagonism. We used the obligate
      pollination mutualism between yuccas and yucca moths to examine the origins of a
      nonpollinating cheater moth, Tegeticula intermedia, and its pollinating sister
      species, T. cassandra. Based on geographic distribution and ecological factors
      affecting the pollinators, previous research had indicated that the cheaters
      evolved in Florida as a result of sympatry of T. cassandra and another pollinator
      species. We used mitochondrial DNA (mtDNA) sequences and amplified fragment
      length polymorphism (AFLP) data to investigate the phylogeographic history of the
      pollinator-cheater sister pair and to test whether the cheaters arose in Florida.
      Contrary to predictions, phylogenetic and population genetic analyses suggested
      that the cheaters evolved in the western United States and subsequently spread
      eastward. Western populations of cheaters had the most ancestral haplotypes and
      the highest genetic diversity, and there was also significant genetic structure
      associated with a geographic split between eastern and western populations. In
      comparison, there was evidence for weak genetic structure between northern and
      southern pollinator populations, suggesting a long history in Florida. The
      western origin of the cheaters indicated that the pollinators have more recently
      become restricted to the southeastern United States. This was supported by AFLP
      analyses that indicated that the pollinators were more closely related to the
      western cheaters than they were to geographically proximate cheaters in the east.
      Shared mtDNA between pollinators and eastern cheaters suggested hybridization,
      possibly in a secondary contact zone. The results negate the out-of-Florida
      hypothesis and reveal instead a long, complex, and disparate history for the
      pollinator-cheater sister pair.

PMID- 15562690
TI  - Costs of an induced immune response on sexual display and longevity in field
      crickets.
AB  - Immune system activation may benefit hosts by generating resistance to parasites.
      However, natural resources are usually limited, causing a trade-off between the
      investment in immunity and that in other life-history or sexually selected
      traits. Despite its importance for the evolution of host defense, state-dependent
      fitness costs of immunity received little attention under natural conditions. In
      a field experiment we manipulated the nutritional condition of male field
      crickets Gryllus campestris and subsequently investigated the effect of an
      induced immune response through inoculation of bacterial lipopolysaccharides.
      Immune system activation caused a condition-dependent reduction in body
      condition, which was proportional to the condition-gain during the preceding food
      supplementation period. Independent of nutritional condition, the immune insult
      induced an enduring reduction in daily calling rate, whereas control-injected
      males fully regained their baseline level of sexual signaling following a
      temporary decline. Since daily calling rate affects female mate choice under
      natural conditions, this suggests a decline in male mating success as a cost of
      induced immunity. Food supplementation enhanced male life span, whereas the
      immune insult reduced longevity, independent of nutritional status. Thus, immune
      system activation ultimately curtails male fitness due to a combined decline in
      sexual display and life span. Our field study thus indicates a key role for
      fitness costs of induced immunity in the evolution of host defense. In
      particular, costs expressed in sexually selected traits might warrant the honest
      advertisement of male health status, thus representing an important mechanism in
      parasite-mediated sexual selection.

PMID- 15562691
TI  - From micro- to macroevolution through quantitative genetic variation: positive
      evidence from field crickets.
AB  - Quantitative genetics has been introduced to evolutionary biologists with the
      suggestion that microevolution could be directly linked to macroevolutionary
      patterns using, among other parameters, the additive genetic variance/ covariance
      matrix (G) which is a statistical representation of genetic constraints to
      evolution. However, little is known concerning the rate and pattern of evolution
      of G in nature, and it is uncertain whether the constraining effect of G is
      important over evolutionary time scales. To address these issues, seven species
      of field crickets from the genera Gryllus and Teleogryllus were reared in the
      laboratory, and quantitative genetic parameters for morphological traits were
      estimated from each of them using a nested full-sibling family design. We used
      three statistical approaches (T method, Flury hierarchy, and Mantel test) to
      compare G matrices or genetic correlation matrices in a phylogenetic framework.
      Results showed that G matrices were generally similar across species, with
      occasional differences between some species. We suggest that G has evolved at a
      low rate, a conclusion strengthened by the consideration that part of the
      observed across-species variation in G can be explained by the effect of a
      genotype by environment interaction. The observed pattern of G matrix variation
      between species could not be predicted by either morphological trait values or
      phylogeny. The constraint hypothesis was tested by comparing the multivariate
      orientation of the reconstructed ancestral G matrix to the orientation of the
      across-species divergence matrix (D matrix, based on mean trait values). The D
      matrix mainly revealed divergence in size and, to a much smaller extent, in a
      shape component related to the ovipositor length. This pattern of species
      divergence was found to be predictable from the ancestral G matrix in agreement
      with the expectation of the constraint hypothesis. Overall, these results suggest
      that the G matrix seems to have an influence on species divergence, and that
      macroevolution can be predicted, at least qualitatively, from quantitative
      genetic theory. Alternative explanations are discussed.

PMID- 15562692
TI  - Predator-driven phenotypic diversification in Gambusia affinis.
AB  - Predation is heterogeneously distributed across space and time, and is presumed
      to represent a major source of evolutionary diversification. In fishes, fast
      starts--sudden, high-energy swimming bursts--are often important in avoiding
      capture during a predator strike. Thus, in the presence of predators, we might
      expect evolution of morphological features that facilitate increased fast-start
      speed. We tested this hypothesis using populations of western mosquitofish
      (Gambusia affinis) that differed in level of predation by piscivorous fish. Body
      morphology of G. affinis males, females, and juveniles diverged in a consistent
      manner between predatory environments. Fish collected from predator populations
      exhibited a larger caudal region, smaller head, more elongate body, and a
      posterior, ventral position of the eye relative to fish from predator-free
      populations. Divergence in body shape largely matched a priori predictions based
      on biomechanical principles, and was evident across space (multiple populations)
      and time (multiple years). We measured maximum burst-swimming speed for male
      mosquitofish and found that individuals from predator populations produced faster
      bursts than fish from predator-free populations (about 20% faster). Biomechanical
      models of fish swimming and intrapopulation morphology-speed correlations
      suggested that body shape differences were largely responsible for enhanced
      locomotor performance in fish from predator populations. Morphological
      differences also persisted in offspring raised in a common laboratory
      environment, suggesting a heritable component to the observed morphological
      divergence. Taken together, these results strongly support the hypothesis that
      divergent selection between predator regimes has produced the observed phenotypic
      differences among populations of G. affinis. Based on biomechanical principles
      and recent findings in other species, it appears that the general
      ecomorphological model described in this paper will apply for many aquatic taxa,
      and provide insight into the role of predators in shaping the body form of prey
      organisms.

PMID- 15562693
TI  - How much of the variation in adaptive divergence can be explained by gene flow?
      An evaluation using lake-stream stickleback pairs.
AB  - How much of the variation in adaptive divergence can be explained by gene flow?
      The answer to this question should objectively reveal whether gene flow generally
      places a substantial constraint on evolutionary diversification. We studied
      multiple independent lake-stream population pairs of threespine stickleback
      (Gasterosteus aculeatus). For each pair, we quantified adaptive divergence based
      on morphological traits that have a genetic basis and are subject to divergent
      selection. We then estimated gene flow based on variation at five unlinked
      microsatellite loci. We found a consistent and significant pattern for
      morphological divergence to be positively correlated with genetic divergence and
      negatively correlated with gene flow. Statistical significance and the amount of
      variation explained varied within and among traits: 36.1-74.1% for body depth and
      11.8-51.7% for gill raker number. Variation within each trait was the result of
      differences among methods for estimating genetic divergence and gene flow.
      Variation among traits likely reflects different strengths of divergent
      selection. We conclude that gene flow has a substantial effect on adaptive
      divergence in nature but that the magnitude of this effect varies among traits.
      An alternative explanation is that cause and effect are reversed: adaptive
      divergence is instead constraining gene flow. This effect seems relatively
      unimportant for our system because genetic divergence and gene flow were not
      correlated with ecologically relevant habitat features of lakes (surface area) or
      streams (width, depth, flow, canopy openness).

PMID- 15562694
TI  - Reconstruction of parental microsatellite genotypes reveals female polyandry and
      philopatry in the lemon shark, Negaprion brevirostris.
AB  - Because sharks possess an unusual suite of reproductive characteristics,
      including internal fertilization, sperm storage, relatively low fecundity, and
      reproductive modes that range from oviparity to viviparity, they can provide
      important insight into the evolution of mating systems and sexual selection. Yet,
      to date, few studies have characterized behavioral and genetic mating systems in
      natural populations of sharks or other elasmobranchs. In this study, highly
      polymorphic microsatellite loci were used to examine breeding biology of a large
      coastal shark, the lemon shark, Negaprion brevirostris, at a tropical lagoon
      nursery. Over six years, 910 lemon sharks were sampled and genotyped. Young were
      assigned into sibling groups that were then used to reconstruct genotypes of
      unsampled adults. We assigned 707 of 735 young sharks to one of 45 female
      genotypes (96.2%), and 485 (66.0%) were assigned to a male genotype. Adult female
      sharks consistently returned to Bimini on a biennial cycle to give birth. Over
      86% of litters had multiple sires. Such high levels of polyandry raise the
      possibility that polyandry evolved in viviparous sharks to reduce genetic
      incompatibilities between mother and embryos. We did not find a relationship
      between relatedness of mates and the number of offspring produced, indicating
      that inbreeding avoidance was probably not driving pre- or postcopulatory mate
      choice. Adult male sharks rarely sired more than one litter at Bimini and may
      mate over a broader geographic area.

PMID- 15562695
TI  - Contrasting patterns of quantitative and neutral genetic variation in locally
      adapted populations of the natterjack toad, Bufo calamita.
AB  - The relative importance of natural selection and genetic drift in determining
      patterns of phenotypic diversity observed in nature is still unclear. The
      natterjack toad (Bufo calamita) is one of a few amphibian species capable of
      breeding in saline ponds, even though water salinity represents a considerable
      stress for them. Results from two common-garden experiments showed a pattern of
      geographic variation in embryonic salinity tolerance among populations from
      either fresh or brackish environments, consistent with the hypothesis of local
      adaptation. Full-sib analysis showed increased variation in survival among
      sibships within population for all populations as osmotic stress was increased
      (broad-sense heritability increased as salinity raised). Nevertheless, toads
      native to the brackish water environment had the highest overall survival under
      brackish conditions. Levels of population genetic differentiation for salinity
      tolerance were higher than those of neutral genetic differentiation, the latter
      obtained through the analysis of eight microsatellite loci. Microsatellite
      markers also revealed little population differentiation, lack of an isolation-by
      distance pattern, and moderate gene flow connecting the populations. Therefore,
      environmental stress tolerance appears to have evolved in absence of geographic
      isolation, and consequently we reject the null hypothesis of neutral
      differentiation.

PMID- 15562696
TI  - Constraints on the morphological evolution of marsupial shoulder girdles.
AB  - Throughout their evolutionary histories, marsupial mammals have been
      taxonomically and morphologically less diverse than their sister taxa the
      placentals. Because of this, it has been proposed that the evolution of
      marsupials has been constrained by the functional requirements of their mode of
      reproduction. Marsupials give birth after short gestation times to immature
      neonates that immediately crawl, under the power of their precociously developed
      shoulder girdles, to the teat where they attach and complete their early
      development. Using a novel approach incorporating adult and embryological
      morphological data, this study is the first to both: (1) statistically support
      adult patterns of morphological divergence consistent with the constraint
      hypothesis, and (2) identify ontogenetic patterns of morphological change that
      demonstrate that the constraint was responsible, at least in part, for their
      formation. As predicted by the marsupial constraint, the shoulder girdles of
      adult marsupials are less diverse than those of adult placentals, and adult
      marsupial scapulae are less morphologically diverse than adult marsupial pelves.
      Furthermore, marsupials that complete an extensive crawl to the teat are
      restricted to a common pattern of ontogenetic scapular shape change, strongly
      supporting the hypothesis that the morphological development of the marsupial
      scapula has been limited evolutionarily by its obligate role in the crawl to the
      teat. Because this study establishes that ontogenetic and evolutionary
      morphological change is correlated within mammalian scapulae, it is probable that
      the marsupial constraint also restricted the morphological divergence of the
      scapula over evolutionary time by limiting ontogenetic change in the scapula.
      These findings, coupled with the importance of the shoulder girdle in mammalian
      locomotor specialization, support the conclusion that the low morphological
      diversity of marsupial forms over evolutionary time could be directly due to the
      constraint on marsupial morphological evolution caused by the functional
      requirements of the crawl to the teat.

PMID- 15562697
TI  - Offspring quality in relation to excess flowers in Pultenaea gunnii (Fabaceae).
AB  - The wider choice hypothesis suggests that hermaphroditic plants increase their
      female fitness by producing excess flowers, exposing more ovaries to the scrutiny
      of selective abortion, and thereby increasing the offspring quality obtained from
      the best, which escape abortion. Selective discrimination of fruit maturation has
      been well documented in many angiosperm species, but there has been no
      examination of how offspring quality varies in relation to the number of excess
      flowers. This relation must be positive over the entire range of excess flower
      number for the wider choice mechanism to be the selective force behind the
      evolution of very large excess floral displays. I examined offspring quality in
      relation to natural variation in nonfruiting flowers in 72 plants of Pultenaea
      gunnii, an Australian bush pea. Maximum seed mass and maximum seedling height at
      30 days growth showed a nonlinear, saturating relation to excess flower number
      that is consistent with a theoretical model of wider choice. But the strongly
      diminishing marginal benefits of excess flowers in this relation make it unlikely
      that wider choice plays a major role in the evolution of floral display size in
      this species.

PMID- 15562698
TI  - Genetic correlation between melanization and antibacterial immune responses in a
      natural population of the malaria vector Anopheles gambiae.
AB  - The immune system of invertebrates can mount different responses, including
      melanotic encapsulation and several antibacterial defense mechanisms. Variation
      of the efficacies of these responses is generally considered to be a product of
      the evolutionary pressure on each response due to infection by parasites.
      However, potential interactions and trade-offs among the different responses of
      the immune system could constrain the evolutionary potential of each response. In
      a natural population of the mosquito Anopheles gambiae, we measured the genetic
      association between the melanization response and an antibacterial response in
      two environmental qualities (well-fed and undernourished larvae). In both
      environments the two immune responses were positively genetically correlated: in
      full-sib families that were most likely to melanize a bead, injected bacteria
      were most likely to be cleared. Thus, our data do not support the idea of a trade
      off among different outcomes of the invertebrate immune system, but rather that
      some families are overall immunologically superior to others.

PMID- 15562699
TI  - To what extent do different types of sex ratio distorters interfere?
AB  - Within the Diptera, two different selfish genetic elements are known to cause the
      production of female-biased sex ratios: maternally inherited bacteria that kill
      male zygotes (male-killers), and X chromosomes causing the degeneration of Y
      bearing sperm in males (meiotic drive). We here develop a mathematical model for
      the dynamics of these two sex-ratio distorters where they co-occur. We show that
      X chromosome meiotic drive elements can be expected to substantially lower the
      equilibrium frequency of male-killers and can even lead to their extinction.
      Conversely, male-killers can also decrease the equilibrium frequency of X drivers
      and cause their extinction. Thus, we predict that there will be some
      complementarity in the incidence of X chromosome meiotic drive and male-killing
      in natural populations, with a lower than expected number of species bearing both
      elements.

PMID- 15562700
TI  - [The disease and its control on zingiberaceous plants in South China Botanical
      Garden].
AB  - The common diseases on the zingiberaceous plants and their occurrence and damage
      as well as control have been investigated in the ginger garden of South China
      Botanical Garden recently. The results show that 2 bacterial and 13 fungous
      diseases are common. To control them effectively, cultural methods such as
      selecting loose, fertile soil as planting field with good drainage and proper
      shade; applying healthy and vigor seeds, seedlings and rhizomes for propagation;
      regulating plant density; fertilizing reasonably, practicing in rotation;
      irrigating moderately; sanitizing the field opportunity are mostly recommended.
      The application of chemical and biological pesticides to protect the beneficial
      organisms is also stressed.

PMID- 15562701
TI  - [Study on the relativity between cultivated varieties and quality of Radix
      Glehniae].
AB  - OBJECTIVE: To study the relation between different cultivated varieties and
      quality of Radix Glehniae. METHODS: Polysaccharide, imperatorin and extractives
      in different varieties were detected according to document and Chinese
      Pharmacopeia. RESULTS: Each content of soluble carbohydrate, rough
      polysaccharide, total carbohydrate, water extractives and alcohol extractives in
      Baitiao is significantly higher than that in other two varieties (P < 0. 05). The
      content of imperatorin is highest in Dahongpao P < 0.05). CONCLUSION: It is more
      effective for Baitiao to restrain humor immunity,cell immunity and the overgrowth
      of T and B cells. Dahongpao is dominani as sedative, spasmolytic and abti
      asthmatic.

PMID- 15562702
TI  - [Medicinal plant resources in habitation of Yugu nationality].
AB  - The medicinal plant resources in habitation of Yugu nationality at Gansu Province
      were investigated by on-the-spot investigation, visitation and collecting
      specimens. This paper reported the distributions of 31 main species and 12
      distinctive medicinal plants. The references of further exploitation and
      utilization were supplied.

PMID- 15562703
TI  - [Direct identification of Retinervus Citri Reticulatae from its confused species
      by FTIR].
AB  - In this paper, direct and accurate identification of Retinervus Citri Reticulatae
      and its confused species has studied. The IR of Retinervus Citri Reticulatae and
      its confused species were obtained by Fourier Transform Infrared Spectrum
      directly. Obvious characteristics for its identification in FTIR were revealed,
      which can be used to identify Retinervus Citri Reticulatae and its confused
      Reticulatae and its confused species were directly, fastly and accurately
      identificated by FTIR.

PMID- 15562704
TI  - [Studies on chemical constituents of Salvia roborowskii Maxim].
AB  - OBJECTIVE: To study the chemical constituents from Salvia roborowskii Maxim.
      METHODS: Chromatography and spectroscopic analysis were employed to isolate and
      elucidate the chemical constituents in the plant. RESULTS: Six compounds were
      isolated and elucidated as lupeol (I), 11 beta-hydroxy-lupeol(II),3 beta-acetyl
      11 beta-hydroxy-lupeol(III), ursolic acid (IV), beta-sitosterol(V), daucosterol
      (VI). CONCLUSION: I approximately VI were isolated from this plant for the first
      time.

PMID- 15562705
TI  - [Studies on chemical constituents of Caesalpinia decapetala (Roth) Alston].
AB  - OBJECTIVE: To study the chemical constituents from Caesalpinia decapetala (Roth)
      Alston. METHODS: Chromatography and spectroscopic analysis were employed to
      isolate and elucidate the chemical constituents in the plant. RESULTS: Seven
      compounds were isolated and elucidated as lupeol acetate(I), lupeol(II), oleanoic
      acid(III), pentacosanoic acid 2,3-dihydroxypropyl ester(IV), 1-(26
      hydroxyhexacosanoyl)-glycerol(V), stigmasterol(VI), beta-sitosterol(VI).
      CONCLUSION: I approximattely VII were isolated from this plant for the first
      time.

PMID- 15562706
TI  - [The effect of Kadsura heteroclita on the cultured hippocampal neurons].
AB  - OBJECTIVE: The effects of different concentration Kadsura heteroclita extract
      (HS2) on the growth of newborn rat hippocampal neurons were observed by means of
      dissociated cell culture. METHODS: The newborn rat hippocampal neurons were
      cultured with different level HS2. The convert phase microscope was used to
      analyse the number and the length of neurites, as well as the maximum diameter of
      hippocampal neurons soma. The survival neurons count and LDH assay were carried
      out to investigate the effect of HS2 on the growth and development of neurons in
      different culture time. RESULTS: After 36h, the number and the length of neurites
      of 1 mg/ml HS2 group were increased and the maximum diameter of hippocampal
      neurons soma did not change. The 0.2 mg/ml HS2 group did not show statistical
      difference as compared with the control group, while 8 mg/ml HS2 inhibited
      notably the growth of neurons. The number of survival neurons of 1 mg/ml HS2
      group was more than that of the control group, and the LDH activity of 1 mg/ml
      HS2 group was lower in different culture time. CONCLUSION: This study suggested
      that suitable dose HS2 can promote the growth and development of hippocampal
      neurons.

PMID- 15562707
TI  - [Effects of genistein on proliferation and differentiation of cultured
      osteoblasts in vitro].
AB  - OBJECTIVE: To study the effects of genistein on proliferation and differentiation
      of cultured osteoblasts in vitro. METHODS: MTT and PNPP were used separately to
      observe the proliferation and the activity of ALP of osteoblasts cultured in
      vitro with different concentration genistein for different incubation periods.
      Protein was measured by Lowry method. RESULTS: It was found that genistein had
      the effects on promoting proliferation of osteoblasts cultured for 24 h and 48 h
      at concentration ranging from 1 x 10(-9) mol/L to 1 x 0(-5) mol/L. The activity
      of ALP was stimulated by genistein at concentration ranging from 1 x 10(-7) mol/L
      to 1 x 10(-5) mol/L after 72 h incubation. CONCLUSION: Genistein has the effects
      on stimulating the proliferation and differentiation of cultured osteoblasts in
      vitro.

PMID- 15562708
TI  - [Study on antiradiation effect of panaxatriol].
AB  - OBJECTIVE: To study antiradiation effect of panaxatriol (PT) and to provide an
      experiment basis for developing relative radiation-resistant skin care products.
      METHODS: Mice were treated with PT or normal saline (the control group) before X
      ray irradiation and were to observe the number of chromosme aberrations killed 3
      hours after irradiation. The chromosome samples of bone marrow cells were
      prepared and chromatid mutation as well as aberrant cells. RESULTS: PT can reduce
      the frequency of chromatid mutative induced by X-ray. Antiradiation effect was
      positively correlated with the dose of PT and the duration of drug, and
      negatively correlated with the dose of X-rays. CONCLUSION: PT has significant
      antiradiation effect.

PMID- 15562709
TI  - [Bone mineral density and biomechanical effects of Chinese herbal drug
      Yanhuogubao on experimental osteoporosis in rats].
AB  - OBJECTIVE: To explore bone mineral density and biomechanical effects of Chinese
      herbal drug Yanhuogubao on steroid hormone-induced osteoporosis in rats. METHODS:
      Male, 3-month-old Sprague-Dawley rats were randomly divided into 4 groups (n =
      7), the basal group, the age control group, the hormone group (4.5 mg/kg
      prednisone acetate, twice a week) and Yanhuogubao (1.5 g/kg/d) group. The bone
      mineral densities and the mechanical characters measurements of femurs and 5th
      lumbar vertebrae in every group were made by using DEXA and SWD-10 electronic
      universal material testing machine. RESULTS: The bone mineral densities on femora
      and 5th lumbar vertebrae in hormone group decreased, and the loads imposed on the
      femoral trunk in three-point bending test decreased by 17.1% (P < 0.05), though
      the rest parameters tended to decrease in comparison with control group. In the
      meantime, Yanhuogubao can prevent prednisone acetate-induced the bone mineral
      densities and mechanical characters of femurs and lumbar vertebrae in rats from
      decline, compared with hormone group. CONCLUSION: When steroid hormone was used
      for a long time, the bone mineral densities and mechanical characters of femora
      and 5th lumbar vertebrae in the rats would be led to decrease, on the contrary,
      Yanhuogubao could arrest the decline of bone mineral densities and mechanical
      characters of rat skeleton.

PMID- 15562710
TI  - [Study on TLC profile of Pheretima aspergillum and Pheretima (Dilong) injection].
AB  - A set of characteristics (profiles) of Pheretima aspergillum and Pheretima
      (Dilong) injection were obtained from thin layer chromatography. It provides
      scientific method for identification and quality evaluation of Pheretima
      aspergillum and Pheretima (Dilong) injection.

PMID- 15562711
TI  - [Optimizing the ultrasonic extraction of tannin in Elaeagnus angustifolia L. by
      uniform design].
AB  - The influences of ultrasonic frequency and ultrasonic time on the extraction rate
      of Tannin in Elaeagnus angustifolia L. were studied. The optimizing had been got.
      Results showed that the ultrasonic extraction method of Tannin in Elaeagnus
      angustifolia L. could save time, improve extraction rates, and need not be hot.
      Compared with traditional extraction, the ultrasonic extraction method is a good
      way.

PMID- 15562712
TI  - [The clinical study on Dan Shao Tang in treating simple hematuria of masked
      nephritis of deficiency of Yin with damp-heat symptom].
AB  - OBJECTIVE: To explore the effect of Dan Shao Tang (DST) in treating simple
      hematuria of masked nephritis of deficiency of Yin with damp-heat symptom.
      METHODS: Sixty patients of simple hematuria of masked nephritis of deficiency of
      Yin with damp-heat symptom were divided into two groups in random, 35 patients in
      treatment group were treated with Dan Shao Tang and westen medicine, and 25
      patients in control group were treated only with western medicine. The effect,
      change of hematuria and immunity index of the two groups were observed three
      months later. RESULTS: The total efficiency of treatment group (65.71%) is better
      than that of control group (36%). Treatment group is obviously better than
      control group on decreasing hematuria and improving immune function. CONCLUSION:
      Dan Shao Tang is effective to treatment on simple hematuria of masked nephritis
      of dificiency of Yin with damp-heat symptom effectively.

PMID- 15562713
TI  - [Isozymes variations among the germplasm resources of Houttuynia in Sichuan].
AB  - The peroxidase and esterase isozymes of the germplasm resources of Houttuynia in
      Sichuan were analyzed. The results showed that it existed plentiful isozymes
      variations among the germplasm resources of Houttuynia in Sichuan. The cultivated
      populations had the same isozymes band types as the wild ones. There were 6
      different types of peroxidase isozymes bands and 10 different esterase isozymes
      band totally. Each peroxidase band type was composed of 4 to 6 bands, and
      esterase isozymes had 5 to 8 bands. There was no significant difference between
      Houttuynia cordata and Houttuynia emeiensis populations in their isozymes bands
      types. The results also showed that the number of peroxidase isozymes bands in
      northern areas was somewhat higher than that in southern areas. However, esterase
      isozymes band types had no geographic differences.

PMID- 15562714
TI  - [Effects of various organic fertilizers on growth and mineral nutrient absorption
      of Morindar officinalis].
AB  - OBJECTIVE: To study the effects of various organic fertilizers on the growth and
      the mineral nutrient absorption of Morindar officinalis. METHOD: The growing
      character and the mineral nutrition contents were determined with conventional
      assay methods. RESULT: The influences of four kinds of fertilizers on the
      bionomics and nutrient absorption of M. officinalis successively were: biotic
      organic fertilizer A > biotic organic fertilizer C > biotic organic fertilizer B
      > farm manure. CONCLUSION: Different kinds of organic fertilizers could
      facilitate the growth and the mineral nutrient absorption of M. officinalis.
      Increasing the fertilizer amount of germ manure could promote the absorption of
      mineral nutrients and the accumulation of dry matters in plants.

PMID- 15562715
TI  - [Morphological and histological study on Pteris multifida].
AB  - The thesis studies on the pharmacognostical characteristics of Pteris multifida
      were carried out in this paper. The blade has special vein-like cell. The stomas
      in dorsal epidermis are regular. The petiol has V-shaped amphicribral bundles.
      The rhizome has 6-8 meristeles. The triangle-form spore has tumor-shaped or
      pellet-shaped decorations on its surface.

PMID- 15562716
TI  - [To identify human and sheep placentas by FT-IR and RP-HPLC techniques].
AB  - Placenta has a long history of being Chinese traditional medicine. The quality
      control methods used nowadays in the markets were mainly based on the amino acid
      content of the placenta. However, it is hard to distinguish human placenta from
      sheep placenta with these methods. In this paper, a novel method was established
      employing FT-IR and RP-HPLC techniques. This method can distinguish human
      placenta from sheep placenta and may help to improve quality control of placenta
      in the markets.

PMID- 15562717
TI  - [Chromatographic identification of a compound similar to ferulic acid in the
      decoction of Herb Leonuri].
AB  - OBJECTIVE: To identify whether there is ferulic acid in decoction of Herb
      Leonuri. METHODS: By TLC and HPLC. RESULTS: The chromatogram of the sample showed
      a dark brown fluorescent spot at the same Rf value of ferulic acid in TLC
      identification test. The retention time of a peak in the HPLC of the sample
      corresponded to that of ferulic acid. CONCLUSION: There is a compound which is
      very similar to ferulic acid in the decoction of Herb Leonuri.

PMID- 15562718
TI  - [Determination of hypoxanthine and xanthine in hippocampus by HPLC method].
AB  - OBJECTIVE: A method was established for the determination of hypoxanthine and
      xanthine in Hippocampus by HPLC. METHODS: The HPLC system consisted of a Kromasil
      C18 column (250 mm x 4.6 mm, 5 microm) with methanol-water (2:98, V/V) as the
      mobile phase. The wavelength of detection was 254 nm. RESULTS: The linear range
      of hypoxanthine and xanthine were 29.0-464.0 ng (r = 0.99996) and 24.5-392.0 ng
      (r = 0.9995) respectively. The average recovery of hypoxanthine was 100.73%, RSD
      = 1.31% (n = 6). The average recovery of xanthine was 100.54%, RSD = 1.14% (n =
      6). CONCLUSION: This method is convenient and the result is accurate. It can be
      used for quality control of Hippocampus.

PMID- 15562719
TI  - [The extraction and effects on mouse lymphocyte proliferation of immunoregulation
      components from Lysimachia hemsleyana].
AB  - OBJECTIVE: To study the effects of extracted fractions from the whole plants of
      Lysimachia hemsleyana Maxim on the proliferation ability of lymphocytes in mice
      in vitro. METHODS: We extracted the components by using of ethanol, ether from
      petroleum, chloroform, ethyl acetate and n-butanol, successively then study them
      on the proliferation of lymphocytes in mice. RESULTS: The n-butanol fraction
      obviously inhibited the proliferation of spleen lymphocytes induced by LPS,
      bilaterally regulated the T lymphocyte proliferation induced by ConA. The
      chloroform fraction markedly enhanced the lymphocytes proliferation induced by
      ConA or LPS. CONCLUSION: The results suggested that n-butanol fraction and
      chloroform fraction from Lysimachia hemsleyana possibly maybe have
      immunoregulation effects.

PMID- 15562720
TI  - [Effect of tongbiling on the expression of MCP-1 mRNA of synovial cells in rats
      with adjuvant arthritis].
AB  - OBJECTIVE: To study the effect of tongbiling, a complex preparation of Chinese
      traditional medicine, on the expression of MCP-1 mRNA of synovial cells in rats
      with adjuvant arthritis. METHOD: The expression level of MCP-1 mRNA in
      synoviocytes from rats with adjuvant arthritis was assayed by the method of RT
      PCR. RESULT: The amounts of MCP-1 mRNA expression in synoviocytes from rats with
      adjuvant arthritis were distinctly decreased by tongbiling. It suggested that
      tongbiling had inhibition effect on rheumatoid arthritis by a down regulation for
      the expression of MCP-1 mRNA in the inflamed synoviocytes.

PMID- 15562721
TI  - [The effects of twenty-one traditional Chinese medicines on tyrosinase].
AB  - OBJECTIVE: To study the effects of 21 kinds of traditional Chinese medicines on
      tyrosinase. METHODS: The catalytic reactive velocity of tyrosinase was determined
      by vision spectrophotometry so as to evaluate the upregulation of traditional
      Chinese medicines extracts. RESULTS: 21 time-curves of catalytic reaction of
      tyrosinase were obtained. CONCLUSION: 13 kinds of traditional Chinese medicines
      extracts in vitro showed a upregulation to tyrosinase activity (P < 0.01).
      Scutellaria baicalensis and Cremastra appendiculata showed a better upregulation
      to tyrosinase activity.

PMID- 15562722
TI  - [Effect of the extract from Peristrophe roxburghiana on hemorheology in rats].
AB  - OBJECTIVE: To observe the effect of extract from Peristrophe roxburghiana (EPR)
      on the hemorheology and thrombosis in rats. METHODS: To study the hemorheology by
      adrenaline and ice-water stimulant and to observe thrombosis by the carotid and
      jugular bypath. RESULTS: EPR could effectively decrease many hemorheologic
      parameters in hypostasis rats and reduce the wet weight of thrombosis.
      CONCLUSIONS: EPR can improve the hemorheological parameters and inhibit the
      formation of thrombosis.

PMID- 15562723
TI  - [An experimental study on treatment of osteoarthritis with herbal compound
      capsule].
AB  - OBJECTIVE: To observe the effect of herbal compound capsule on knee arthritis.
      METHOD: Right knee arthritis model was established by knotting right femoral
      vein, so as to observe drug action. RESULTS: Compared with model group, herbal
      compound capsule could reduce intraosseous pressure, cardiac whole blood
      viscosity, plasma viscosity and concentration of nitric oxide, and inhibit
      degenerative changes of arthral cartilage. CONCLUSION: The herbal compound
      capsule can inhibit experimental osteoarthritis.

PMID- 15562724
TI  - [The effects of Radix Puerariae decoction on levels of antibody and interleukin-2
      in mice].
AB  - OBJECTIVE: To study the effects of Radix Puerariae on immune response. METHOD:
      Decoction of Radix Puerariae was administrated to mice (i.g.), and then sheep red
      blood cell (SRBC) and ovalbumin were used as antigens. Levels of anti-SRBC, anti
      ovalbumin antibodies and serum interleukin-2 (IL-2) were determined. RESULT:
      Levels of anti-SRBC, anti-ovalbumin antibodies were higher in experimental group
      than that in control group (P < 0.05), while concertrations of IL-2 showed no
      significant difference. CONCLUSION: Decoction of Radix Puerariae can promote the
      formation of antibody.

PMID- 15562725
TI  - [Determination of tetrandine content in tetrandine microsphere].
AB  - OBJECTIVE: To determine the contents of tetrandine in tetrandine microsphere for
      the quality control of the preparation. METHOD: Tetradine in microsphere was
      determined by spectrophotometry of standard curve. RESULT: The content of
      tetrandine was 44.5% +/- 0.26% (n=3). CONCLUSION: The method was simple, rapid
      and accurate.

PMID- 15562726
TI  - [Study concept of traditional Chinese medicine quality standards].
AB  - Chinese medicinal materials quality was controlled mainly by modern analytic
      approach, secondly by traditional identification method, popularizing based on
      improvement. Chinese medicine prepared slice quality was controlled mainly by
      traditional identification method, secondly by modern analytic approach,
      improving based on popularization.

PMID- 15562727
TI  - Prevalence of mental retardation among children in Saudi Arabia.
AB  - This survey determined the prevalence and regional distribution of mental
      retardation among children in Saudi Arabia. Data were analysed from a population
      based national survey conducted during 1996-99, in which 60,630 children aged up
      to 18 years were screened using IQ tests and questionnaires completed by
      physicians. The prevalence of mental retardation was 8.9 per 1000 children, a
      rate similar to that reported in other countries. Moderate or severe retardation
      was classified in 70.9% of these children. Of the mentally retarded children in
      the 0-18 years age range, 83.2% were not attending school. Special educational
      programmes are needed to improve the quality of life of mentally retarded
      children.

PMID- 15562728
TI  - Relationship between depression and non-adherence to anticoagulant therapy after
      valve replacement.
AB  - Management of anticoagulant therapy after mechanical valve replacement is
      difficult in developing countries because of patient non-adherence. The effect of
      depression on adherence to drug therapy and to a clinic visit schedule was
      evaluated for 62 patients who received prostheses. All were prescribed a once-per
      day regimen of warfarin and were scheduled for three appointments at the
      anticoagulant clinic for dose adjustment at 3-week intervals. According to the
      Center for Epidemiological Studies Depression Scale, 22 were depressed. Non
      depressed patients were more compliant than depressed patients; adherence was
      inversely correlated with depression scores. While depression had no relationship
      with age, sex and cardiac symptoms, there was a relationship with anxiety and
      poor social support.

PMID- 15562729
TI  - Psychiatric disorders among adolescent Jordanian returnees from Kuwait during the
      1991 Gulf War.
AB  - Adolescent Jordanian returnees from Kuwait during the 1991 Gulf War were expected
      to have elevated rates of psychiatric disorders, therefore their mental health
      status was examined. We evaluated 1376 newly enrolled students in two public
      universities in northern Jordan using an Arabic translation of the self
      administered General Health Questionnaire. The overall rate of psychiatric
      disorders among the study sample was 23.3%; the rate among adolescent returnees
      (30.8%) was significantly higher than among other adolescents (22.4%). Although
      psychiatric disorders were generally common among Jordanian adolescents, the
      exposure of Jordanian children in Kuwait to the Gulf War was still detrimental to
      their mental health status as adolescents.

PMID- 15562730
TI  - Determination of cadmium, lead, copper and zinc in Yemeni khat by anodic
      stripping voltammetry.
AB  - Trace element concentrations in khat were investigated as they can disturb trace
      element levels in the body. Cadmium (Cd), lead (Pb), copper (Cu) and zinc (Zn)
      levels in khat and 6 leafy vegetables commonly consumed in the Republic of Yemen
      were determined by differential pulse anodic stripping voltammetry after wet
      digestion of the organic matter. Khat had significantly higher concentrations of
      Cu and Zn than did the leafy vegetables, but similar amounts of Cd and Pb. The
      average daily intake of khat consumers of Cd, Pb, Cu and Zn from khat only was
      estimated to be 2.0-10.2 microg/day, 23.6-118.0 microg/day, 530-2654 microg/day
      and 662-3311 microg/day respectively. Although high, these values were within
      Food and Agriculture Organization/World Health Organization tolerance limits.

PMID- 15562731
TI  - Cytogenetic profile of Down syndrome in Alexandria, Egypt.
AB  - During 1992-2001, 673 Down syndrome patients were referred to the Department of
      Human Genetics in Alexandria. Regular (free) trisomy 21 constituted 95.4% of
      cases; Robertsonian translocation 2.7%; and mosaicism 0.7%. In 8 cases, regular
      trisomy 21 was associated with structural or numerical chromosome anomalies.
      Translocation was parentally inherited for 33.3% of cases and maternal
      transmission was twice as common as paternal. Two translocated Down syndrome
      fetuses were diagnosed prenatally in a t(14;21) carrier mother. Mean maternal age
      was high in regular trisomy 21 (38.2 years) but not in translocation (25.3
      years). There was an excess of males in all groups except the mosaic group where
      the male:female ratio was 0.67. Cytogenetic investigations assist in patient
      management and family counselling.

PMID- 15562732
TI  - Frequency of haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency
      in Basra.
AB  - Basra, southern Iraq, was mapped for haemoglobinopathies and glucose-6-phosphate
      dehydrogenase (G6PD) deficiency. Of 1064 couples aged 14-60 years recruited from
      the Public Health Laboratory, 49 had beta-thalassaemia trait, 69 had sickle-cell
      trait, 2 had haemoglobin D trait, 2 had haemoglobin C trait and 1 had high
      persistent fetal haemoglobin. Carriers of major beta-globin disorders comprised
      11.48%. G6PD deficiency was detected in 133 individuals (12.5%). Only 10 couples
      (0.94%) were at risk of having children affected with either sickle-cell disease
      or beta-thalassaemia major. These defects constitute a real health problem and
      necessitate a management plan and public health education for early diagnosis and
      therapy.

PMID- 15562733
TI  - Prevalence of endocrine complications in beta-thalassaemia major in the Islamic
      Republic of Iran.
AB  - To identify the prevalence of endocrine dysfunction in Iranians with beta
      thalassaemia, we assessed thyroid, parathyroid, pancreatic and adrenal function
      in 150 beta-thalassaemic patients aged 10-22 years at the Paediatrics Unit,
      Shiraz University of Medical Sciences. Primary hypothyroidism was found in 6.0%
      of patients (mean age: 14.6 +/- 1.9 years), hypoparathyroidism in 7.3% (14.5 +/-
      3.2 years), type 1 diabetes mellitus in 7.3% (13.9 +/- 2.8 years) and adrenal
      insufficiency in 1 patient. The relatively high frequency of endocrine
      dysfunction found in our study may be a result of poor disease control and
      management in early life when irreversible tissue damage occurs due to iron
      overload. These findings reinforce the importance of regular follow-up of
      patients with beta-thalassaemia major for early detection and management of
      associated complications.

PMID- 15562734
TI  - Essential fatty acid status in infants and children with chronic liver disease.
AB  - The relationship between essential fatty acid (EFA) status and degree of
      hyperbilirubinaemia and oxidant stress in infants and children with chronic liver
      diseases was evaluated. Thirty patients with chronic cholestasis and 30 with
      liver cirrhosis were examined; 30 healthy subjects served as controls. Patient
      groups had significant decreases in EFAs and significant elevation of total
      bilirubin. Levels of thiobarbituric acid reactive substances were significantly
      raised and were significantly inversely correlated to decreased EFA levels. There
      were also significant decreases in retinol, alpha-tocopherol and alpha
      tocopherol/total lipids ratio, which had significant positive correlations with
      decreased EFA levels. Infants and children with chronic liver diseases have a
      high risk of EFA deficiency correlated with progressive elevation of serum
      bilirubin and progressive deterioration of oxidant status.

PMID- 15562735
TI  - Clustering of cardiovascular risk factors among obese urban schoolchildren in
      Sousse, Tunisia.
AB  - Against a background of increasing obesity among Tunisians, we conducted a
      transversal survey of 1569 children aged 13-19 years selected by multistage
      cluster sampling to evaluate the prevalence of obesity and clustering of
      cardiovascular risk factors among obese schoolchildren in the urban area of
      Sousse. Obese children were found to have higher blood pressure, higher
      triglyceride levels and lower high-density lipoprotein cholesterol levels than
      children of normal weight. In both genders, the mean height and weight across all
      age groups was significantly higher in urban than in rural children. Our study
      indicates that obesity and the adverse effects of being over the ideal body
      weight are no longer limited to industrialized countries.

PMID- 15562736
TI  - Smoking among secondary-school boys in Bahrain: prevalence and risk factors.
AB  - To determine the prevalence of smoking among male secondary school students in
      Bahrain and to identify their risk factors for smoking, we surveyed a random
      sample of students by questionnaire. The prevalence of smoking was 26.6%, 25.5%
      and 25.4% among first-year, second-year and third-year students respectively.
      Cigarettes (21.0%), water-pipes (13.0%) and cigars (1.6%) were popular. Smokers
      and non-smokers had similar socioeconomic profiles, but differed in degree of
      disapproval of smoking shown by close contacts and whether close contacts were
      smokers. The prevalence of smoking among male secondary-school students in
      Bahrain did not decline despite intense anti-smoking efforts in the last decade,
      perhaps indicating the effectiveness of tobacco advertising and promotions that
      target youth.

PMID- 15562737
TI  - [Knowledge, attitudes and behaviours of women towards breast cancer screening].
AB  - The objective of this study was to describe knowledge, attitudes and behaviour of
      women towards breast cancer screening methods in two regions of north Tunisia.
      Thus 936 women from Ariana (urban region) and 993 women from Zaghouan (rural
      region) were selected and answered a questionnaire on their perception of the
      gravity of breast cancer, the vulnerability of women, the efficacy of screening
      and their use of screening. The use of screening was significantly more frequent
      in Ariana for both clinical breast examination and mammography, but screening use
      was modest. This low use of breast cancer screening contrasts with a positive
      attitude to breast cancer screening methods. The factors positively associated
      with use of screening were urban residence, age between 35 and 49 years,
      educational level and the perception that cancer treatment had advanced in
      Tunisia.

PMID- 15562738
TI  - Patterns of belief and use of traditional remedies by diabetic patients in Mecca,
      Saudi Arabia.
AB  - A sample of 1039 diabetic patients in Saudi Arabia was interviewed using a
      structured questionnaire about belief in traditional herbal remedies. The
      relationship of belief scores to sociodemographic and diabetes-related variables
      was assessed using chi-square tests. The study showed that 15.6% of the sample
      believed that traditional medicines were safe and effective and 25.8% that they
      might be beneficial. One-third of patients were using traditional remedies. A
      statistically significant relationship was shown between belief in traditional
      medicines and variables such as female sex, positive family history of diabetes,
      duration of diabetes and compliance with diet. However, there was no relationship
      with other compliance variables or with glucose and weight control. Efforts
      should be made to enhance diabetic education among patients on the basis of
      evidence-based practice.

PMID- 15562739
TI  - New method for the fixation of the endotracheal tube in patients with facial
      hair.
AB  - A problem faced by anaesthetists in Islamic countries is the unwillingness of
      patients to shave their facial hair. Adhesive tapes may not adequately secure an
      endotracheal tube in these patients, and a cotton band around the neck may cause
      obstruction of the venous return. A new device, a synthetic leather mask, was
      compared with the two other methods in a randomized trial on 900 patients
      undergoing general anaesthesia. No displacement of the endotracheal tube,
      pressure on the neck veins, or skin reaction were observed in the mask group
      compared with the adhesive tape and the cotton band groups. The mask can be
      reused, autoclaved and made in several sizes, prevents allergies to adhesive tape
      and is suitable for laryngoscopy, suctioning and inserting the oral airway.

PMID- 15562740
TI  - Pain tracker diagnostic instrument: effect on patients' satisfaction with their
      interactions with the primary care physician.
AB  - In a randomized trial, the pain tracker instrument was evaluated as a diagnostic
      screening tool and for its effect on patients' satisfaction with their
      interactions with the primary care physician. The instrument form was filled in
      by the physician after asking the study patients about symptoms. Control (n = 53)
      and study patients (n = 49) were interviewed and the instrument's effect was
      analysed from responses to 15 statements. The pain tracker group were
      significantly more satisfied with the physician relationship than were controls
      (mean satisfaction score 85 +/- 8 versus 61 +/- 9). A direct linear correlation
      was found between patients' assessment of the visit and overall satisfaction (r =
      0.86). The pain tracker can be an important component in history taking and a
      useful diagnostic screening tool in pain presentations.

PMID- 15562741
TI  - Prevalence of iodine deficiency disorders in the United Arab Emirates measured by
      raised TSH levels.
AB  - The United Arab Emirates National Screening Programme for Congenital
      Hypothyroidism was established in January 1998. The programme measures neonatal
      thyroid-stimulating hormone (TSH) levels of blood samples collected on filter
      paper on day 5 by heel prick. The prevalence of raised TSH levels (> 5 microU/mL
      whole blood) during 1998 and 1999 was used to evaluate the degree of iodine
      deficiency disorders (IDD) in the population in different regions. The ratio of
      TSH profile in the present study and goitre rate in schools in a 1994 study were
      discrepant, although there was good correlation between the ratio of TSH profile
      and urinary iodine. The prevalence of raised TSH levels was < 3% in the Emirates
      overall, which is normal, and IDD varied from mild to normal problems in
      different regions.

PMID- 15562742
TI  - [Food intake during and outside Ramadan].
AB  - We explored the effect of fasting in the month of Ramadan on the dietary pattern
      of a group of 130 healthy adults. During Ramadan, there was an increase in total
      energy intake, as a result of protein and lipid intake but not carbohydrate
      intake compared to the diet througout the rest of the year, in both students and
      parents. The meal eaten after sunset was an important contributor to calories
      (65%), lipids (74%), proteins (71%) and carbohydrates (56%). These findings show
      the eating behaviour during Ramadan may contribute to improved nutritional status
      of people at risk of nutritional deficiency.

PMID- 15562743
TI  - Effect of natural starters used for sourdough bread in Morocco on phytate
      biodegradation.
AB  - Phytase activity was studied in natural sourdough bread starters to determine
      physicochemical characteristics (phytic acid hydrolysis, dough rising capacity
      and pH) in the flour and during sourdough fermentation. Fermentation
      microorganisms (yeasts and lactic acid bacteria) were also characterized. Results
      showed a decrease of phytic acid in sourdoughs started with traditional starters,
      and wide variation in phytase activity. Microorganism counts were high at the end
      of fermentation, indicating higher fermenting activity of the starters. Yeast
      populations showed wide variation and lactic acid bacteria had high counts in the
      fermentation. Phytase activity was demonstrated in starter cultures made of
      lactic acid bacteria and yeast isolates, the most interesting of which were
      Saccharomyces cerevisiae combined with Lactobacillus plantarum and Leuconostoc
      mesenteroides.

PMID- 15562744
TI  - Prevalence of rubella antibodies among schoolgirls in Sana'a, Republic of Yemen.
AB  - To determine the prevalence of rubella antibodies and age of exposure to rubella
      among Yemeni schoolgirls, we studied the sera samples of 323 female students (age
      range 11-21 years; mean age 16.26 +/- 1.89 years) drawn from three schools in
      Sana'a. All samples were screened for rubella IgG antibodies using enzyme linked
      immunosorbent assay and, if negative, for IgM in order to exclude the possibility
      of recent exposure. Of 323 sera, 296 (91.64%) were positive for rubella IgG. All
      IgG negative sera were also IgM negative. Comparable antibody prevalence was
      observed in all age groups. The prevalence of rubella IgG among Yemeni
      schoolgirls is high, with most becoming immune between the ages of 11 and 21
      years. Although the age of exposure seems to be < or = 13 years, further
      investigation is needed to confirm this.

PMID- 15562745
TI  - Effect of gender on reporting of MMR adverse events in Saudi Arabia.
AB  - We evaluated the safety of a measles-mumps-rubella (MMR) immunization campaign
      for Saudi children (age range: 6-13 years) and gender differences in reporting
      post-MMR adverse events. After vaccinations were administered, we monitored 160
      schools for 14 days and 19 hospitals in the 8 cities under study for 10 weeks.
      Incidence rates were: all MMR adverse events, 26.5/10,000 MMR vaccines
      (significantly higher in females than males); Urabe strain aseptic meningitis,
      1.0/295,000; fever, 40.2/10,000 (females) and 0.9/10,000 (males); and parotitis,
      5.4/10,000 (females) and 0.9/10,000 (males). Combined MMR vaccine containing the
      Urabe mumps strain was safe for children aged 6-13 years. Gender differences
      regarding reactogenicity were evident and should be considered when designing
      future studies.

PMID- 15562746
TI  - First report of Escherichia coli O157 among Iraqi children.
AB  - We determined the prevalence of enterohaemorrhagic Escherichia coli, especially
      E. coli O157, and other enteropathogens among 200 children with bloody diarrhoea
      and 100 age-matched controls at two Baghdad hospitals. Bacterial and parasitic
      agents were found in 39.5% and 28.5% of cases, respectively; no pathogen was
      detected in 32%. E. coli O157 was identified in 11.5% and more than one pathogen
      was found in 15.5% of cases. The most common pathogens were enteropathogenic E.
      coli (EPEC) (5%); E. coli other than E. coli O157 or EPEC (15%); Entamoeba
      histolytica (25%) and Giardia lamblia (3.5%). All isolates of E. coli O157:H7
      were sensitive to cephalexin, ciprofloxacin, gentamicin and nalidixic acid and
      resistant to erythromycin, polymyxin B and vancomycin. Resistance to 6 or more
      antimicrobial agents was common (50% of isolates).

PMID- 15562747
TI  - Helicobacter pylori and rosacea.
AB  - Recent reports have suggested an increased prevalence of Helicobacter pylori
      infection in patients with rosacea, with some evidence of dermatological
      improvement in patients treated with antibiotics for this infection. Our study
      investigates the prevalence of H. pylori infection in rosacea patients in Kerman.
      Serological examination was done for 29 patients with classical identification of
      rosacea using the enzyme-linked immunosorbent assay IgG antibody method.
      Comparison of antibody titres with those of a control group revealed that the
      prevalence of positive serological tests for H. pylori was significantly higher
      in the test group. This supports the suggestion of some form of relationship
      between rosacea and H. pylori infection, though further investigations with
      larger sample sizes are required for a definite conclusion.

PMID- 15562748
TI  - Beta-haemolytic streptococci in acute pharyngitis.
AB  - To determine the role and importance of beta-haemolytic streptococci in acute
      pharyngitis and its relative susceptibility to antibiotics, we cultured samples
      from 143 patients (age range: 3-72 years) who presented over a 5-month period in
      2001 at three primary health care centres in Sousse, Tunisia. The cultures
      yielded 80 beta-haemolytic streptococci (59 group A streptococci and 21 non-group
      A streptococci). All strains were susceptible to benzylpenicillin, amoxicillin,
      chloramphenicol, rifampicin and pristinamycin. Susceptibility was variable in
      erythromycin, tetracycline, fosfomycin, telithromycin and levofloxacin. Minimum
      inhibitory concentrations were determined by E-test for penicillin, erythromycin
      and levofloxacin. Our results confirm that penicillin is still the reference
      treatment for acute pharyngitis. However, to minimize the potential for
      complications arising from its use, continued vigilance is required.

PMID- 15562749
TI  - Prevalence of antibody to Brucella species in butchers, slaughterers and others.
AB  - Brucellosis is being reported with increasing frequency in the Islamic Republic
      of Iran. Serum antibodies in high-risk and general populations help to define cut
      off levels and can be used as a simple and rapid diagnostic tests in infected
      areas. We performed the rose Bengal test (RBT), serum agglutination test (SAT)
      and 2-mercaptoethanol (2ME) titre determination on 415 healthy individuals
      including butchers, slaughterers and others. Positive results were found by RBT,
      SAT titre (1:80) and 2ME titre > or = 1:20 in slaughterers (10%, 20% and 6%
      respectively), butchers (6%, 4% and 1% respectively) and the general population
      (1%, 2% and < 1% respectively). A single SAT titre > or = 1:80 in the presence of
      2ME titre > or = 1:20 can be diagnostic in this region.

PMID- 15562750
TI  - Use of thermonuclease testing to identify Staphylococcus aureus by direct
      examination of blood cultures.
AB  - Blood cultures submitted to the Clinical Microbiology Laboratory, Queen Alia
      Military Hospital, Amman during 1999-2001 were examined to evaluate
      thermonuclease testing for identifying Staphylococcus aureus in blood culture
      broths growing gram-positive cocci. Of 170 cultures studied, 129 yielded gram
      positive staphylococci and 41 yielded other gram-positive cocci. Toluidine blue
      deoxynucleic acid agar plates were used to test for thermonuclease activity.
      Standard tube coagulase tests were performed on the isolates. Direct detection of
      thermonuclease activity in 76 blood culture broths containing gram-positive
      staphylococci showed 100% correlation with subsequent tube coagulase tests. The
      thermonuclease test provides a fast, specific and reliable confirmation of S.
      aureus bacteraemia by direct examination of blood culture broths that contain
      gram-positive cocci. This allows for timely, optimal antibiotic therapy.

PMID- 15562751
TI  - Evaluation of the community-oriented medical education in two medical schools in
      Sudan.
AB  - An evaluation was made of the extent and impact of community-oriented medical
      education in the Khartoum and Gezira medical schools in the Sudan. Competency of
      graduates 3-7 years after graduation and health indicators of the provinces of
      both medical schools were examined. Gezira had a more community-oriented
      curriculum although it was deficient in other aspects. The degree of partnership
      of both schools with the Ministry of Health and the community was weak and the
      schools' research programmes had no community orientation. Graduates had similar
      profiles of job satisfaction, community service, knowledge, attitudes and self
      learning. Although Gezira had more emphasis on community medical education,
      graduates of both schools adapted themselves to the environment dictated by the
      health care delivery system and cultural values.

PMID- 15562752
TI  - Validity of using bovine teeth as a substitute for human counterparts in adhesive
      tests.
AB  - Shear and tensile bond strengths of 40 human and 40 bovine teeth were compared.
      Teeth were randomly assigned to group I, which received light-cured composite
      resin, or group II, which received light-cured resin-reinforced glass ionomer
      cement. The groups were subdivided for shear and tensile bond strength tests,
      which were conducted on a universal testing machine installed to a computer
      transducer. Statistical analysis revealed a highly significant difference between
      shear and tensile bond strengths of human and bovine enamel; however, regression
      prediction equations support the use of bovine teeth as a reliable substitute to
      human counterparts in bonding studies of orthodontic adhesion.

PMID- 15562753
TI  - Bone infection.
AB  - Osteomyelitis, or bone infection, affects all age groups and develops from
      various sources including haematogenously from distant infection foci, from
      external sources such as post-operative or post-traumatic wound infections and
      from adjoining soft tissue infections. Staphylococcus aureus, Streptococcus
      pyogenes and Haemophilus influenzae are the most common pathogens of
      haematogenous osteomyelitis. Aerobic and facultative gram-negative bacteria have
      emerged as significant pathogens in some types of osteomyelitis while anaerobic
      bacteria are increasingly recognized as potential pathogens in non-haematogenous
      osteomyelitis. The emergence of antibiotic resistance is of increasing concern,
      although improvements in radiologic imaging, antibiotic treatment and heightened
      awareness have led to earlier detection such that long-term sequelae and
      morbidity are now primarily due to delays in diagnosis and inadequate treatment.

PMID- 15562754
TI  - Psychosis in a patient with Usher syndrome: a case report.
AB  - The present report is the case of a 26-year-old man, born with Usher syndrome.
      The patient had had a significant hearing impairment since birth and had
      developed retinitis pigmentosa. He had originally been diagnosed with a
      depressive disorder and treated with antidepressants, with no subsequent
      improvement in his mental state. Following a deterioration in his mental state he
      was admitted for reassessment at the Queen Elizabeth Psychiatric Hospital,
      Birmingham, and antidepressants were stopped. It subsequently became apparent
      from observations, interviews with the patient and information from the patient's
      carers and relatives that he had a psychotic illness. Treatment was started with
      the antipsychotic drug risperidone, after which he showed significant
      improvement. The association between Usher syndrome and psychosis is discussed.

PMID- 15562755
TI  - Disease prevention.

PMID- 15562756
TI  - [Nano-ESI-MS/MS identification on differentiation-associated proteins in M1 mouse
      myeloid leukemia cells induced by IL-6].
AB  - OBJECTIVE: To identify two differentiation-associated proteins induced by rhIL-6
      in M1 mouse myeloid leukemia cells. METHODS: Protein spots were excised from 2-D
      gels and digested in-gel with trypsin. The trypsin lysis products were first
      analyzed by matrix-assisted laser desorption/ionization-time of flight-mass
      spectrometry (MALDI-TOF-MS) through peptide mass fingerprinting and then
      performed peptide sequencing by nano-electrospray ionization mass
      spectrometry/mass spectrometry (nano-ESI-MS/MS). The database search was finished
      with the Mascot search engine (http://www.matrixscience.co.uk) using the data
      processed through MaxEnt3 and MasSeq. RESULTS: The two proteins were not revealed
      by peptide mass fingerprint using MALDI-TOF-MS, while they were respectively
      identified as Destrin and Putative protein after the sequence of their trypic
      peptides were obtained by the nano-ESI-MS/MS techniques. CONCLUSION: Nano-ESI
      MS/MS technique can successfully identify the two differentiation-associated
      proteins induced by rhIL-6 and has great advantage in protein analysis.

PMID- 15562757
TI  - [BAY11-7082 and Lactacystein in CD154-induced NF-kappaB activation].
AB  - OBJECTIVE: To investigate the inhibition mechanisms of BAY11-7082 (IkappaB-alpha
      phosphorylation inhibitor) and Lactacystein (proteosome inhibitor) in CD154
      induced NF-kappaB activation. METHODS: We used recombinant CD154 to stimulate
      EBV/LMP1 negative Ramos B cell and observed the effects of BAY11-7082 and
      Lactacystein in CD154-induced NF-kappaB luciferase activation, phosphorylation
      and degradation of IkappaB-alpha, phosphorylation of p65, and nuclear
      translocation of NF-kappaB subunits upon CD154 stimulation. RESULTS: Both BAY11
      7082 and Lactacystein abrogated CD154-induced NF-kappaB luciferase activation in
      Ramos cells. While CD154-induced phosphorylation of p65, phosphorylation and
      degradation of IkappaB-alpha, and nuclear translocation of p50, p65, and c-Rel
      were all blocked by BAY11-7082; Lactacystein only inhibited degradation of
      IkappaB-alpha and p65 nuclear translocation. CONCLUSION: BAY11-7082 and
      Lactacystein inhibit CD154-induced NF-kappaB activation through different
      mechanisms.

PMID- 15562758
TI  - [Role of PD153035 in the induction of apoptosis of XG-1 myeloma cell line].
AB  - OBJECTIVE: To study the role of epidermal growth factor receptor (EGFR) in the
      proliferation and survival of human myeloma cells. METHODS: The inhibitor of
      EGFR, PD153035, was used to block the signal transduction of EGFR. The
      proliferation and apoptosis of myeloma cell line, XG-1, were detected by 3H-TCR
      incorporation assay and Annexin V staining analysis, respectively. The
      phosphatation of STAT3, the key activate signal to the myeloma cell
      proliferation, was detected with Western blot. RESULTS: PD153035 decreased the
      proliferation of XG-1 and induced an obvious apoptosis in XG-1. The phosphatation
      of STAT3 induced by HB-EGF but not by IL-6 was blocked by PD153035. CONCLUSION:
      The proliferation and survival of myeloma cells may be suppressed by PD153035 due
      to the blockage of phosphatation of STAT3 induced by the activation of EGFR.

PMID- 15562759
TI  - [Preparation, identification, and analysis on tissue chips of polyclonal anti
      peptide antibody to chemokine-like factor 1].
AB  - OBJECTIVE: To prepare the polyclonal anti-peptide antibody against chemokine-like
      factor1 (CKLF1) and apply it to the expression and functional studies of CKLF1.
      METHODS: CKLF1 was analyzed with bioinformatics methods. The 16 amino acids
      sequence peptide was selected from CKLF1 C terminal end. Antibody was raised by
      immunizing rabbits with the peptide conjugated to keyhole limpet hemocyanin
      (KLH). RESULTS: A high titer polycolonal antibody was obtained from the rabbit
      against the peptide. ELISA analysis proved that the titer of rabbit serum against
      anti-peptide of CKLF1 was up to 10(-4). Western blot analysis revealed that it
      could react not only with recombinant CKLF1 expressed in a cell-Free Protein
      Biosynthesis System and Drosophila S2 cells, but also recognize the endogenous
      CKLFs in the tissue array. Positive staining was detected in the normal bronchial
      cartilage, gastric mucosa, and gastric smooth muscle tissues. Normal rectum and
      well-differentiated rectal carcinoma showed strong positive staining, but the
      poor-differentiated rectal carcinoma samples revealed negative staining.
      CONCLUSION: The anti-peptide antibody can specifically recognize CKLFs and may be
      a useful reagent for the detection of CKLF1.

PMID- 15562760
TI  - [Prediction and identification of autoepitopes of PDC-E2 specific CD8+ CTL in
      primary biliary cirrhosis patients].
AB  - OBJECTIVE: To identify autoepitopes of E2 subunit of pyruvate dehydrogenase
      complex (PDC-E2) specific CD8+ CTL in primary biliary cirrhosis (PBC) patients.
      METHODS: An online database SYFPEITHI was applied to predict HLA-A*0201
      restricted epitopes which located in PDC-E2 30-50 aa and 150-190 aa where B-cell
      epitopes clustered with CD4+ T-cell epitopes. T2 cell line reconstitution and
      stabilization assay, induction of specific CTL lines from peripheral blood
      mononuclear cells (PBMCs) of patients with PBC and cytotoxicity of peptides
      induced CTL were performed to screen the epitopes from those candidates. RESULTS:
      Five potential epitopes were predicted by database. Of the 5 candidates, two
      peptides 159-167 aa and 165-174 aa, with highly binding activity to HLA-A*0201
      molecules, could stimulate PBMCs from most HLA-A*0201 positive PBC patients to
      proliferate and peptide-induced CTL lines showed specific cytotoxicity.
      CONCLUSION: Peptides of KLSEGDLLA (159-167 aa) and LLAEIETDKA (165-174 aa) in the
      inner lipoyl domain of PDC-E2 are HLA-A*0201 restricted CD8+ CTL immunodominant
      epitopes in PBC.

PMID- 15562761
TI  - [Genetic association between interleukins gene polymorphisms with primary biliary
      cirrhosis in Chinese population].
AB  - OBJECTIVE: To determine the relationship between polymorphisms in the genes
      encoding IL-1, IL-6, and IL-10 with primary biliary cirrhosis (PBC) in Chinese
      population. METHODS: Whole-blood samples were taken from 77 patients with PBC and
      160 healthy controls. DNA was extracted and the polymorphisms at positions IL-1
      +3953, IL-1RN intron 2, IL-6 -174, and IL-10 -1082, -819, and -592 were
      determined by using sequence-specific polymerase chain reaction (SSP) or
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: The frequency of IL-1RN1,1 allele in PBC group was significantly higher
      than in control group (90.9% vs 79.4%, P=0.026), and the frequency of IL-1RN1,2
      in PBC group was significantly lower than in control group (6.5% vs 18.8%,
      P=0.013). There was no significant difference in the frequence of IL-1RN*2 allele
      between PBC group and control group (P=0.06). Of the 77 patients with PBC, 4
      patients were IL-6 -174GC, 73 were IL-6 174GG. All the 160 health controls are IL
      6 -174GG (P=0.0036). The frequence of IL-6 -174C allele in PBC group was
      significantly higher than that in control group (P=0.0038). No significant
      differences of polymorphisms for IL-1 +3953 and IL-10 (-1082, -819 and -592) were
      found between PBC group and control group. CONCLUSION: The polymorphisms of IL
      1RN and IL-6 -174G/C appear to be associated with PBC, and the polymorphisms of
      IL-1 +3953 and IL-10 promoter gene are not associated with PBC in a Chinese
      population.

PMID- 15562762
TI  - [Regulation of Fc receptor expression by immune complexes on neutrophils and U937
      cells].
AB  - OBJECTIVE: To study the regulation of Fc receptor expression by immune complexes
      (ICs) on neutrophils and U937 cells. METHODS: IgA ICs, IgG1 ICs, IgG2 ICs, IgG3
      ICs, IgG4 ICs, and IgM ICs were incubated with neutrophils or U937 cells for 1 h.
      Then their surface Fc receptors were stained by anti-Fc gammaR I, anti-Fc gammaR
      II , anti-Fc gammaR III, and anti-Fc alphaR I monoclonal antibodies and analyzed
      by fluorescent activated cell sorting (FACS). RESULTS: IgG1 ICs and IgG3 ICs up
      regulated Fc gammaR II and Fc gammaR III on U937 cells, Fc gammaR I and Fc alphaR
      I on neutrophils. Almost all ICs down-regulated Fc gammaR II on neutrophils.
      CONCLUSIONS: ICs can regulate Fc receptor expression on neutrophils and U937
      cells, among which IgG1 ICs and IgG3 ICs are most effective.

PMID- 15562763
TI  - [Cloning and expression of a homologue of human macrophage migration inhibitory
      factor from P. falciparum 3D7].
AB  - OBJECTIVE: To clone and express a homologue of human macrophage migration
      inhibitory factor (MIF) from P. falciparum 3D7--PfMIF. METHODS: The nucleotide
      sequence of PfMIF was found through blast P. falciparum genomic sequence
      databases with the amino acid sequence of human MIF (HuMIF). RT-PCR, DNA
      sequencing, and bioinformatics analysis were used for the cloning of Pfmif gene.
      The recombinant protein was expressed in E. coli and purified through the
      affinity column. RESULTS: The full length of Pfmif gene was cloned and sequenced.
      It was composed of 351 nucleotides and encoded 116 amino acids with the typical
      characteristic of MIF family. The recombinant protein was successfully expressed
      and purified. CONCLUSIONS: The Pfmif gene and recombinant protein were
      successfully isolated and PfMIF was preliminarily identified as a novel member of
      MIF family.

PMID- 15562764
TI  - [Effects of nitric oxide on mitochondrial permeability transition and cytochrome
      C of human hepatocellular carcinoma cell lines].
AB  - OBJECTIVE: To investigate the effects of nitric oxide on mitochondrial
      permeability and cytochrome C (cyt C) of human hepatocellular carcinoma cell
      lines. METHODS: NO-mediated apoptosis in human hepatocellular carcinoma cell
      lines SMMC-7721 and HepG2 was investigated by flow cytometry. The growth and
      proliferation of human hepatocellular carcinoma cell lines SMMC-7721 and HepG2
      were evaluted by MTT assay. Mitochondrial transmembrane potential was analyzed by
      flow cytometry with double staining of Rh123 and PI, and cytoplasmid cyt C was
      measured by Western blot. The cells were preincubate with cyclosporin A or GSH
      synthesis blocker BSO to explore their effect on the results of the above
      experiments. RESULTS: NO donor sodium nitroprusside (SNP) induced apoptosis in
      human hepatocellular carcinoma cell lines SMMC-7721 and HepG2 and resulted in the
      decrease of the mitochondrial transmembrane potential and the increase of the
      amount of cytoplasmid cyt C in time-dependent manner. Cyclosporin A (CsA)
      specific inhibitor of the mitochondrial permeability transition pore could
      partially prevent the decrease of delta psi m and the release of cyt C. In
      contrast, GSH synthesis blocker BSO promoted the decrease of delta psi m and the
      release of cyt C. CONCLUSIONS: NO may induce apoptosis in human hepatocellular
      carcinoma cell lines SMMC-7721 and HepG2 by decreasing delta psi m, opening the
      mitochondrial permeability transition pore, and releasing the cyt C.

PMID- 15562765
TI  - [Chemotherapeutic drugs enhanced rsTRAIL tumoricidal activity].
AB  - OBJECTIVE: To explore the role and mechanisms of chemotherapeutic drugs in TRAIL
      induced cell death. METHODS: Tumoricidal activities of the chemotherapeutic drugs
      and/or rsTRAIL in 13 strains of tumor cell lines were evaluated by MTS-PMS assay
      and flow cytometry. DR5 expression in the cells was observed by Western blot.
      RESULTS: The apoptosis of human promyelocytic leukemia cells HL-60, liver cancer
      cells BEL-7402, T-acute lymphoblastic leukemia cells Jurkat, and myeloid leukemia
      cells K562 treated with rsTRAIL at 0.5 microg/ml were 53.20%, 52.20%, 51.54%,
      52.70%, and 41.00%, respectively, while that of the embryonal spleen cells 293
      was 24.00%. However, the apoptosis percentages of lung cancer cells anti 973,
      breast cancer cells MCF-7, Chinese hamster ovarian cancer cells COS-7,
      neuroglialoma cells U251, neuroblastoma cells SH-SY5Y, glioma cells BT-325, rat
      pheochromocytoma cells PC12, and mouse adrenal epithelial cells NIH3T3 were all
      less than 10% under the same conditions. The sensitivity of central neuron cells
      of SH-SY5Y, PC-12, U251, BT3251, and human embryonal spleen cells 293, which were
      not sensitive to rsTRAIL challenges, increased remarkably after treatment with
      CHX, CP, and 8-CA at sub-toxic doses plus rsTRAIL at 0.5 microg/ml. The
      expressions of DR5 were up-regulated and kept pace with the onset of apoptosis in
      the BEL-7402 liver cancer cells. CONCLUSION: The chemotherapeutic drugs including
      CHX, CP, and 8-CA at sub-toxic doses can enhance antitumor activity of rsTRAIL.

PMID- 15562766
TI  - [Screening, cloning, and analyzing for hSNF5 binding proteins in human fetal
      brain].
AB  - OBJECTIVE: To identify novel binding proteins of hSNF5, a subunit of chromatin
      remodeling complex in human fetal brain. METHODS: The yeast two-hybrid system was
      used for this study. Positive cDNA clones were sequenced. Sequence homology and
      putative functional domains were analyzed and compared with databank. RESULTS:
      Nine positive clones obtained were analyzed, among which the sequence of one
      clone was 97% homologous to the 3' mRNA of a hypothetical protein FLJ20643, while
      other four clones were related to protein coding sequences existed in the
      GenBank. The rest four clones were not in frame with any known protein coding
      sequence. CONCLUSIONS: Clones encoding for hSNF5 binding protein exists in cDNA
      library of human brain. These proteins may recruit chromatin remodeling complex
      via hSNF5 to modulate the transcription of their target gene and the related cell
      functions.

PMID- 15562767
TI  - [Heat shock induced transcription of hsp90alpha gene on chromatin template].
AB  - OBJECTIVE: A CAT reporter plasmid (pBLCAT3alpha1) driven by the promoter of
      hsp90alpha was in vitro assembled into chromatin to investigate the transcription
      activity of the reporter gene upon heat shock. METHODS: A competitive RT-PCR
      based technique was used to quantify the promoter activity of hsp90alpha gene on
      chromatin or naked DNA templates in vitro. RESULTS: The in vitro transcription
      efficiency was first optimized by using different amounts of whole cell extracts
      from heat shock-treated HeLa cells. In vitro chromatin assembly was carried out
      with purified components of chromatin assembly associated factors, core histones
      and CAT reporter gene driven by the promoter of hsp90alpha gene. Results showed
      that chromatin formation repressed the in vitro transcription of the gene.
      CONCLUSION: The heat shock induced transcription of hsp90alpha gene on chromatin
      template is more efficient than that on naked DNA in vitro.

PMID- 15562768
TI  - [Genetic analysis of 17 biallelic markers on Y chromosome in 3 Chinese ethnic
      group populations].
AB  - OBJECTIVE: To study the genetic polymorphism of Y chromosome in different Chinese
      ethnic group populations. METHODS: Genotypes of 17 biallelic markers located in
      the nonrecombining portion of the Y chromosome in 76 men from 3 Chinese ethnic
      group populations (Han in Shandong, Bai in Yunnan, and Tu in Qinghai) were
      examined with polymerase chain reaction (PCR) and allelic-specific PCR (ASPCR).
      Their haplotypes made of these 17 binary markers were constructed. The principle
      component (PC) analysis was conducted based on the haplotype frequency
      distribution among these 3 and other 15 published Chinese ethnic group
      populations. RESULTS: The diversities of M50, M110, M103, M88, M3, and M7 were
      not found in these 3 populations. The frequencies of YAP+ were 23.8%, 6.7%, and
      4% respectively in Tu, Bai, and Shandong Han. Eleven haplotypes were found in 3
      populations--7 haplotypes (H1, H3, H5, H6, H8, H9, and H11) in Shandong Han
      (Han.SD), 8 haplotypes (H1, H2, H3, H5, H6, H8, H11, and H16) in Tu, and 9
      haplotypes (H1, H3, H4, H5, H6, H8, H9, H11, and H13) in Bai. The predominant
      haplotypes were H1, H3, H5, H6, H8, and H11. According to PC analysis, Bai was
      close to Northern Han; Shandong Han, Southern Han (Han.S), Bai and Yunnan Tibetan
      clustered together; and Tu was close to Yi, Hui and Manchurian. CONCLUSIONS:
      Shandong Han may have had genetic exchanges with southern populations in China.
      It has been confirmed that some gene components of Han had flowed into Bai's gene
      pool. Gene flowed from Central Asia had impacted Chinese western populations.

PMID- 15562769
TI  - [Establishment of immortalized cell line BLTR-4 and primary identification of its
      biological character].
AB  - OBJECTIVE: To establish immortalized cell line from the urothelium of the urinary
      bladder and identify the characteristics of the cell line. METHODS: Human
      papillomavirus 16 (HPV-16) plasmid was used to transfect urothelium of infant
      urinary bladder in vitro with the help of Fugene-6, and this plasmid contained E6
      and E7 genes of HPV-16. We also identified the existence of HPV-16 E6 and E7
      genes and the biological characteristics of the cell line by PCR,
      immunohistochemistry, and the biology identification. RESULTS: BLTR-4 cell line,
      produced from the transfection of HPV-16K plasmid, was a cell line from
      urothelium with the expression of HPV-16 E6 and E7 genes. It had been cultured
      more than 70 passages, and the characteristics of growth was similar to the
      immortalized cell line as reported. CONCLUSIONS: BLTR-4 cell line is an
      immortalized cell line from urothelium of the urinary bladder, which contains HPV
      16 E6 and E7 genes. BLTR-4 cell line is a good experimental model to investigate
      the relationship of the infection of high risk HPV and transitional cell
      carcinoma (TCC) in vitro.

PMID- 15562770
TI  - [Polymorphisms on 15 STR loci of Han population in Yan'an].
AB  - OBJECTIVE: To investigate the polymorphisms of 15 STR loci of Han population in
      Yan'an. METHODS: Blood samples were obtained from 100 unrelated Han individuals
      in Yan'an. DNA templates were screened by AmpF/STR Identifiler kit and
      ABI3100Avant DNA analyzer. RESULTS: The allele frequencies of 15 STR loci ranged
      from 0.005 to 0.550, and the genotype frequencies ranged from 0.010 to 0.310. The
      combined match probability was 2.5x10(-17) and combined EPP was 0.999999999.
      CONCLUSIONS: The 15 STR loci used in this study were highly polymorphic in Han
      population in Yan'an and suitable for population study and forensic cases in this
      region.

PMID- 15562771
TI  - [Immunogenicity of mutant and wild HPV16 DNA vaccines].
AB  - OBJECTIVE: To evaluate the efficacy of mutation of human papillomavirus 16
      (HPV16) E7 in two zinc-binding motifs on HPV16 E7 C terminus on antigen-specific
      immunity. METHODS: pcDNA3.1/16E7 and pcDNA3.1/ME7 were successfully constructed
      by inserting the E7 (ME7) into pcDNA3.1 BamH I, EcoR I cut sites. After
      intramuscular injection with pcDNA3.1, pcDNA3.1/16E7, and pcDNA3.1/16ME7 on
      C57BL/6 mice, splenocytes from vaccinated mice was isolated. After have been
      stimulated with E7-specific peptide, interferon gamma (IFN-gamma), interleukin 2
      (IL-2), and cytotoxic T lymphocyte (CTL) were detected by ELISA, Eli-spot, and
      LDH assay respectively; splenocytes without E7 peptide stimulation were used as
      control group. RESULTS: Splenocytes from mice vaccinated with pcDNA/ME7,
      stimulated with E7 peptide, generated significantly larger number of E7-specific
      IL-2 compared with pcDNA3.1/16E7, pcDNA3.1, and control group. The E7-specific IL
      2 generated in pcDNA-ME7 group was 5-fold of that of pcDNA3.1/16E7, and the
      difference was statistically significant (P < 0.05). Splenocytes from mice
      vaccinated with pcDNA/ME7 and stimulated with E7 peptide, generated significantly
      larger number of E7-specific IFN-gamma compared with other vaccines. pcDNA-ME7
      generated a 2-fold increase in the number of E7-specific IFN-gamma compared with
      wild-type E7 and the difference was statistically significant (P < 0.05). The
      highest CTL activity in mice vaccinated with pcDNA/ME7 at an E:T ratio of 45:1
      was achieved compared with mice vaccinated with other vaccines. The percents of
      specific lysis generated by pcDNA3.1/ME7, pcDNA3.1/E7, pcDNA3.1, and without
      vaccination were of (28.7+/-1.2) %, (55+/-2.2) %, (12.5+/-2.0) %, and (11.5+/
      1.2) % respectively, and significant difference existed between the former and
      the latter two groups (P < 0.05). However, no significant difference was found
      among all the groups without specific E7 peptide stimulation (P > 0.05).
      CONCLUSIONS: The mutation of zinc-binding motifs on HPV16 E7 C terminus may
      greatly enhance the immunogenicity.

PMID- 15562772
TI  - [Correlation between DNA load of human papillomavirus and recurrence of condyloma
      acuminata].
AB  - OBJECTIVE: To determine the correlation between DNA load of human papillomavirus
      (HPV) and recurrence of condyloma acuminata (CA). METHODS: The HPV6/11 and
      HPV16/18 DNA load of 31 cases of primary CA and 32 cases of recurrent CA were
      detected by real-time fluorogenic quantitative PCR. RESULTS: Among the 63 CA
      patients, 62 cases were HPV6/11 DNA positive. The positive rate was 98.4%. The
      ranges of HPV6/11 DNA load in primary and recurrent CA were 1.4x10(3)-6.7x10(7)
      copies/ml and 1.2x10(4)-3.6x10(8) copies/ml respectively. Of 62 cases with
      HPV6/11 DNA positive, 7 cases were HPV16/18 DNA positive (11.3%). The ranges of
      HPV16/18 DNA load in primary and recurrent CA were 1.9x10(3)-1.6x10(4) copies/ml
      and 1.4x10(5)-1.7x10(7) copies/ml respectively. The HPV6/11 and HPV16/18 DNA load
      in recurrent CA were higher than in primary CA (P < 0.05). The DNA load of
      HPV6/11 was positively correlated with times of recurrence and course of disease
      (r=0.37 and 0.30 respectively). CONCLUSION: Certain correlation exists between
      DNA load of HPV and recurrence of CA.

PMID- 15562773
TI  - [Construction and identification of recombinant firefly luciferase reporter
      plasmid pGL2-PEPCK-Luc].
AB  - OBJECTIVE: To evaluate in vitro regulation of phosphoenolpyruvate carboxykinase
      (PEPCK) gene promoter on gene transcription, and construct luciferase reporter
      plasmid pGL2-PEPCK-Luc. METHODS: A 550 bp fragment of PEPCK promoter cut from
      plasmid pPEPCK-int was inserted into transitional vector PBS-SK to construct a
      transition plasmid PBS-PEPCK. Then the recombinant luciferase reporter plasmid
      pGL2-PEPCK-Luc was cloned. RESULTS: Restriction enzymes and nucleotide sequence
      conformed that the coupling site of recombinant plasmid was correct without base
      mutation and deletion, and the sequence inserted was the same as data of
      GeneBank. The luciferase could be expressed in hepatoma cell transfected by pGL2
      PEPCK-Luc. CONCLUSION: Established a new means to study transcriptional
      regulation of PEPCK promoter.

PMID- 15562774
TI  - [Effects of phytoestrogen alpha-zearalanol on normal human breast].
AB  - OBJECTIVE: To study the effects of phytoestrogen alpha-zearalanol (alpha-ZAL) on
      normal human breast. METHODS: Ten specimens of normal human breast tissues were
      subcutaneously implanted into 30 athymic nude mice aged 9-10 weeks, one for 3
      mice. These mice were then randomly divided into three groups: control group
      (without hormone treatment, n = 10), 1 mg/kg alpha-ZAL group (n = 10), and 5
      mg/kg alpha-ZAL group (n = 10). All breast tissues were taken out 6 weeks later.
      Immunohistochemistry was used to determine the protein expressions of
      proliferating cell nuclear antigen (PCNA), inhibiting apoptosis gene Bcl-2,
      estrogen receptor (ER), and progesterone receptor (PR). Reverse transcription
      polymerase chain reaction (RT-PCR) was used to measure the expression levels of
      estrogen sulfotransferase (EST) mRNA and bridging integrator protein-1 (BIN1)
      mRNA. Morphological features of grafts before and after treatment were also
      observed. RESULTS: Alpha-ZAL had no significant effects on Bcl-2, PCNA, ER, and
      PR expression of mammary epithelial cells in graft specimens. Alpha-ZAL
      upregulated BIN1 mRNA expression in grafts, but had no significant effect on
      ESTmRNA expression. CONCLUSIONS: Alpha-ZAL does not affect the morphology,
      proliferating, and apoptosis of epithelial cells in normal human breast tissues
      implanted into nude mice, but it may increase the gene expression of tumor
      inhibiting BIN1, suggesting that alpha-ZAL may have potential proteotive effect
      on normal human breast.

PMID- 15562775
TI  - [Effect of combined continued hormone replacement therapy on knee osteoarthritis
      symptom of postmenopausal women].
AB  - OBJECTIVE: To study the effect of combined continued estrogen and progestin
      replacement therapy on knee osteoarthritis (OA) symptoms of postmenopausal women.
      METHODS: Sixty-four postmenopausal women with radiological knee OA and symptoms
      aged 45-75 were divided into treatment group and control group. They were given
      estradiol velerate (E2V) 1.0 mg/d and medroxyprogestetone acetate (MPA) 2 mg/d
      (treatment group) or placebo (control group) for 6 months. Calcium 400 mg/d were
      given to all cases. Then 0-100 mm visual analon scale (VAS) was used to evaluate
      the severity of knee pain at baseline and after 1, 3, 6 month of treatment.
      RESULTS: Significant differences on pain at night and tenderness around knee were
      seen in the treatment group compared with the control group after 1 months of
      treatment (P = 0.036 and 0.035, respectively). The improvement of pain at night,
      during walk and morning stiffness between the two groups showed significant
      difference after 6 months (P = 0.026, 0.027, and 0.011, respectively).
      CONCLUSION: Combined estrogen and progestin replacement therapy can relieve the
      knee OA symptoms of postmenopausal women.

PMID- 15562776
TI  - [Imaging diagnosis and interventional therapy of transplant renal artery
      stenosis].
AB  - OBJECTIVE: To discuss the diagnostic methods of transplant renal artery stenosis
      (TRAS) and clinical outcome following percutaneous transluminal angioplasty.
      METHODS: Of 24 patients with TRAS screened by color Doppler ultrasound and
      confirmed with digital subtraction angiography, balloon angioplasty was performed
      in 19 patients, and 5 patients received stent implantation, including 2 cases of
      recurrent stenosis. RESULTS: Technical success was achieved in all procedures
      with no serious complications. The blood pressure and serum creatinine levels of
      all patients were remarkably decreased (P < 0.01). Renal functions of the two
      patients with restenosis were significantly improved after intra-arterial
      stenting. CONCLUSIONS: Doppler ultrasonography is useful in the screening and
      follow-up of TRAS and arteriography is still the definite diagnostic method.
      Percutaneous transluminal angioplasty and stenting are safe and effective
      procedures to treat TRAS.

PMID- 15562777
TI  - [Imaging diagnosis for fatty liver: a systematic review].
AB  - OBJECTIVE: To systematically assess imaging diagnostic tests for fatty liver and
      provide a decision-making basis for clinical diagnosis and screening. METHODS:
      Electronic searches were conducted on the Chinese Biomedical Database, PubMed,
      and EMBASE, combining with manually searching of Chinese literature. All searches
      were completed until November 2002. All studies which evaluated imaging
      diagnostic test of human fatty liver were included. Data of diagnostic accuracy
      in the included studies were extracted, and methodological quality of the studies
      was assessed independently by two reviewers according to the established quality
      standard. Quantitative analysis or qualitative description were performed based
      on available data. RESULTS: Of 13 studies that met the eligibility criteria, 10
      studies evaluated the diagnostic accuracy of B-mode ultrasound, 3 studies
      evaluated contrast-enhanced (helical) CT. To assess 7 diagnostic test studies for
      fatty liver that used liver biopsy as reference test: the pooled sensitivity of B
      mode ultrasound was 0.89 (95% confidence interval 0.87-0.92), specificity was
      0.94 (95% confidence interval 0.92-0.96) and the Q value was 0.90 by adjusted
      SROC method. To assess 2 diagnostic test studies for fatty liver that used CT as
      reference test: the pooled sensitivity, specificity, and Q value were 0.92 (95%
      confidence interval 0.89-0.96), 0.88 (95% confidence interval 0.84-0.92), and
      0.90 respectively by adjusted SROC method. CONCLUSIONS: B-mode ultrasound method
      can be regarded as an effective method for fatty liver diagnosis and screening.
      The methodologic quality of diagnostic test needs to be improved.

PMID- 15562778
TI  - [Signal transduction and biological characteristics of EB virus-encoded latent
      membrane protein 1 and its correlation with CD40].
AB  - The oncogenic Epstein-Barr virus (EBV) -encoded latent membrane protein 1 (LMP1)
      enables this virus's long-term survival within the cells of immune system. Mean
      while, LMP1 also plays a critical role for the transformation of resting B cells
      by EBV. It initiates the activation of signalling pathways, such as NF-kappaB,
      mitogen-activated protein kinase (MAPK), and JAK/STAT cascade by adaptor proteins
      including the tumor necrosis factor (TNF) receptor associated factors (TRAFs) and
      the TNF receptor associated death domain protein (TRADD). It increases the
      expression of adhesion molecules LFA-1, ICAM-1, and costimulatory molecule B7-1
      of B cells, and regulates the antibody and cytokine secreted by B cells. LMP1 and
      CD40 have many common properties in signal transduction. Both of them co-localize
      in lipid rafts for signal transduction. Considering its close relationship with
      CD40, the research on LMP1 has become a hot spot in the immunology field.

PMID- 15562779
TI  - [Bowel preparation before colorectal surgery: from intestinal mucosal barrier].
AB  - The routine bowel preparation before colorectal surgery usually includes
      mechanical and medicine preparations, with the original purpose of reducing
      complications such as anastomosis leakage, wound, and abdominal infections. Many
      domestic hospitals are still employing the methods of three-day bowel
      preparation, while in the West, the way of this preparation has dramatically
      changed. In last decade, one-day preparation has been widely accepted
      internationally, with two major medications of sodium phosphate and polyethylene
      glycol frequently used in the clinic. It has also been indicated that excessive
      mechanical and medicinal bowel preparations exert harmful effects on the combined
      intestinal barrier, and may result in various complications. A few reports have
      suggested to omit the mechanical bowel preparation before surgery, which is still
      under controversy, however, well-designed clinical trials are needed to readjust
      and regulate the duration and intensity of bowel preparation before colorectal
      surgery in China.

PMID- 15562780
TI  - [Nutritional depletion in chronic obstructive pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is one of the major diseases
      worldwide. Nutritional depletion is a common problem in COPD patients and also an
      independant predictor of survival in these patients. Many data are helpful for
      determining nutritional depletion, including anthropometric measurement,
      laboratory markers, body composition analysis (fat-free mass and lean mass), and
      body weight. The mechanism of nutritional depletion in patients with COPD is
      still uncertain. It may be associated with energy/metabolism imbalance, tissue
      hypoxia, systemic inflammation, and leptin/orexin disorders. In patients with
      nutritional depletion, growth hormone and testosterone can be used for
      nutritional therapy in addition to nutrition supplementation.

PMID- 15562781
TI  - [The HIV vaccine].
AB  - The development of a vaccine that can prevent infection by the human
      immunodeficiency virus or the Acquired Immunodeficiency Syndrome has remained
      elusive despite 20 years of scientific effort. This review analyzes the reasons
      that the development of a vaccine has been so difficult, and proposes a plan to
      work towards an immunological approach to investigating the best vaccine
      candidates in the first world in individuals who are already infected, before
      taking the most promising vaccines to the developing world to attempt to prevent
      infection and disease.

PMID- 15562782
TI  - [Effect of dibutyl phthalate on the biochemical enzymes and lipid peroxidation in
      rat testes].
AB  - OBJECTIVE: To explore the effect of dibutyl phthalate (DBP) on the biochemical
      enzymes and lipid peroxidation in rats. METHODS: Healthy 6-week old male Sprague
      Dawley rats were randomly divided into 4 groups with 16 in each. DBP dissolved in
      peanut oil was administered by gavage at dosages of 0, 250, 500 and 1000 mg/(kg x
      d). After 2- and 4-week DBP exposure, 8 rats in each group were killed, with
      certain organs selected and weighed. The activities of biochemical enzymes and
      glutathione peroxidase (GSH-Px) and the levels of glutathione (GSH) in the serum
      and testis homogenate were determined respectively. RESULTS: DBP induced a rise
      in the liver organ body weight ratio, but a fall in the testis organ body weight
      ratio, and it was significant in the highest exposure group compared with the
      control after either 2-week or 4-week treatment (P < 0.01). After 2-week DBP
      exposure, GSHPx activities in the serum and GSH levels in the testis homogenate
      showed a decreasing tendency, but GSHPx activities increased markedly in the
      testis homogenate (P < 0.05). After 4-week DBP exposure, while alkaline
      phosphatase (ALP) activities in the serum revealed an increasing tendency,
      sorbitol dehydrogenase (SDH) activities were inhibited significantly in both the
      serum and the testis homogenate at the dosage of 1000 mg/(kg x d) compared with
      the control group (P < 0.01). Furthermore, GSH contents in the serum were also
      affected at this dose (P < 0.05). CONCLUSION: The results indicate that DBP
      administration strongly affects the liver and the testis organ body weight
      ratios. Lipid peroxidation is one possible toxic mechanism caused by DBP. SDH may
      be one of the most sensitive toxic indices when exposed to DBP.

PMID- 15562783
TI  - [Quality analysis of the primary semen samples from 512 donors].
AB  - OBJECTIVE: To evaluate the semen quality of the donors. METHODS: The semen
      parameters of the primary samples of 512 donors were examined following the World
      Health Organization (WHO) guide and computer-aided sperm analysis (CASA, product
      by Harmilton Thorne) system. RESULTS: Of the 246 (246/512, 48%) donors with
      potential fertility, only 146 (146/512, 28.5%) came up to the semen standard set
      by the Chinese Ministry of Health, while 266 (266/512, 52%) were below the WHO
      reference values of semen parameters. CONCLUSION: Repeat semen analyses may
      increase the success rate in screening semen donors. The semen quality of the
      donors suggests that it is necessary to pay more attention to male reproductive
      health.

PMID- 15562784
TI  - [Treatment option for unexplained primary infertility following failed
      intrauterine insemination].
AB  - OBJECTIVE: To determine an optimal insemination technique for unexplained
      infertility patients undergoing IVF or ICSI following failed intrauterine
      insemination (IUI). METHODS: Sixty-five cycles of 61 patients with failed IUI
      were divided into four groups: Group A (37 cycles of IVF), Group B (19 cycles of
      ICSI), Group C (4 cycles of IVF and ICSI: half and half), Group D (5 cycles of
      ICSI after failed IVF). The conventional IVF cycles were defined as Group E (37
      cycles), and the conventional ICSI cycles defined as Group F (24 cycles). The
      fertilization rate, completely failed fertilization rate, high quality embryo
      rate, clinical pregnancy rate and the implantation rate were compared among all
      the groups. RESULTS: There were statistically significant differences in the
      fertilization rate, completely failed fertilization rate between Groups A and E
      (55.4% vs 72.8%, P < 0.05; 21.6% vs 0%, P < 0.005), and Groups A and B (55.4% vs
      68.4%, P < 0.05; 21.6% vs 0%, P < 0.01). In Group D, there was statistically
      significant difference in the fertilization rate between IVF cycles and ICSI
      cycles (12.2% vs 74.2%, P < 0.005). CONCLUSION: The present study demonstrates
      that there may be 20% of totally failed fertilization in IVF cycles with
      unexplained primary infertility following failed IUI, and ICSI treatment can
      increase fertilization rate and avoid complete fertilization failure.

PMID- 15562785
TI  - [IL-8 and TNF-alpha in prostatic secretions as indications in evaluating chronic
      prostatitis].
AB  - OBJECTIVE: To investigate the significance of the determination of IL-8 and TNF
      alpha in prostatic secretions in the evaluation of chronic prostatitis. METHODS:
      IL-8 and TNF-alpha levels in EPS were evaluated by ELISA in 90 men: controls (n =
      12), CBP (n = 12), CPPS IIIA (n=38), CPPS IIIB (n=28). And the difference was
      analyzed between CBP or CPPS IIIA and CPPS IIIB or controls. RESULTS: IL-8 and
      TNF-alpha levels in EPS were higher in men with CBP [(10967.5 +/- 3477.7) pg/ml,
      (84.1 +/- 54.7) pg/ml] or CPPS IIIA [(9268.4 +/- 2034.6) pg/ml and (32.6 +/-
      18.6) pg/ml], but lower in men with CPPS IIIB [(2726.1 +/- 277.5) pg/ml, (12.6 +/
      7.1) pg/ml] or controls [(2800.0 +/- 320.2) pg/ml and (12.9 +/- 10.1) pg/ml]
      respectively. There was significant difference between CBP or CPPS IIIA and CPPS
      IIIB or controls (P < 0.01). CONCLUSION: IL-8 and TNF-alpha are elevated in the
      EPS of the men with CBP and CPPS IIIA, and provide a novel means for the
      identification and characterization of chronic nonbacterial prostatitis/chronic
      pelvic pain syndrome. The cut-points for IL-8 and TNF-alpha to discriminate CBP
      or CPPS IIIA from CPPS IIIB or controls need further investigation.

PMID- 15562786
TI  - [Analysis of the diagnostic criteria of bladder outlet obstruction in benign
      prostatic hyperplasia].
AB  - OBJECTIVE: To analyze the value of the diagnostic criteria for bladder outlet
      obstruction in benign prostatic hyperplasia (BPH). METHODS: A total of 358
      patients with BPH were divided into 3 grades according to fibrous
      urethrocystoscopy information on the severity of obstructions, which were
      classified as Grade 1 (slight), Grade 2 (moderate), and Grade 3 (severe). By
      Schafer's graph they were divided into 7 grades, represented by 0 to VI. We
      analyzed the volume of prostate, maximum flow rate (Qmax), residual urine volume,
      International Prostatic Symptom Score (IPSS) and detrusor instability.
      Statistical analysis ANOVA (analysis of variance) was made, spearman correlation
      evaluated and the coefficient of determination measured. RESULTS: Of all the
      patients, 27 were classified as Grade 1, 236 as Grade 2 and 95 as Grade 3. Eighty
      four patients had detrusor instability. The volumes of the prostate ranged from
      16 ml to 145 ml, averaging (47.04 +/- 15.61) ml. The mean maximum flow rate was
      (10.02 +/- 2.12) ml/min and the mean residual urine volume was (84.06 +/- 36.50)
      ml. With the increase of the severity of obstruction, the volume of the prostate
      increased (F = 4.216, P < 0.05), IPSS rose (F = 8.408, P < 0.001), the maximum
      flow rate decreased (F = 22.43, P < 0.001), the residual urine volume rose (F =
      163.232, P < 0.001), the incidence of detrusor instability increased (F = 23.637,
      P < 0.001) and Schafer's grades were elevated (F = 202.897, P < 0.001). The
      volume of the prostate, the maximum flow rate (Qmax), residual urine volume, IPSS
      detrusor instability and Schafer's grades were all correlated significantly with
      the severity of the obstruction. The correlation index and coefficient of
      determination were r = 0.29, R2 = 0.08; r = 0.35, R2 = 0.12; r = -0.69, R2 =
      0.47; r = 0.60, R2 = 0.36; r = 0.33, R2 = 0.11; r = 0.72, R2 = 0.52;
      respectively. The correlation between the urethrocystoscopy information and
      Schafer's graph on the severity of the obstruction were the best criteria of all.
      CONCLUSION: The severity of the obstruction at urethrocystoscopy correlates well
      with that at urodynamic investigation. Such criteria could improve the
      sensitivity and specificity of the diagnosis of bladder outlet obstruction.

PMID- 15562787
TI  - [Effect of electrovaporization on the prostate and its surrounding tissues].
AB  - OBJECTIVE: Transurethral electrovaporization of the prostate (TVP) for benign
      prostatic hyperplasia (BPH) has proven to be efficacious with lower morbidity
      than transurethral resection of the prostate (TURP) on clinical studies. However,
      no histopathologic data are available to support the clinical findings in human
      studies. The following study was done using a canine model in an effort to
      evaluate these histopathologic changes. METHODS: Nine canines received antegrade
      electrovaporization or resection of the prostate, via an open cystoma, using
      Storz series resectoscope and video equipment. The dogs were sacrificed and their
      prostates harvested at 0 week (immediately after operation), 1 week or 5 weeks
      after electrovaporization or resection. The prostates were evaluated grossly as
      well as histologically for cavitary defects and depth of necrosis. RESULTS:
      Prostate examination revealed superficial necrosis (less than 1.8 mm deep) at 0
      week following the 270 watts operation, and less than 3 mm deep necrosis with
      acute inflammation and focal hemorrhage at 1 week. The depths of necrosis were
      less than 1.3 mm and 2.2 mm at 0 week and 1 week after the 180 W
      electrovaporizion. And the 120 W resection resulted in necrosis 1.1 mm and 1.6 mm
      deep at most, which was localized in the vaporized prostate only, with no
      histopathologic change in the surrounding tissues. Epithelial stratification was
      underway by the fifth week, but with inflammation. CONCLUSION: TVP in the canine
      model showed only shallow necrosis at the site of the vaporization. These data
      provide a histopathologic rationale for the minimal morbidity and efficacious
      nature of this technique demonstrated in clinical studies.

PMID- 15562788
TI  - [Outcome of intracytoplasmic injection of epididymal and testicular sperm
      obtained from azoospermic patients].
AB  - OBJECTIVE: To review the treatment results of intracytoplasmic injection of
      epididymal and testicular sperm obtained from 50 azoospermic patients from
      January 2003 to May 2004. METHODS: Sperm was retrieved by percutaneous epididymal
      sperm aspiration (PESA) or testicular sperm extraction (TESE) and
      intracytoplasmic sperm injection (ICSI) was performed. The rates of successful
      sperm retrieval, fertilization, implantation and pregnancy were analysed and
      evaluated. RESULTS: In the PESA, TESE and ejaculation groups, the number of M II
      oocytes suitable for ICSI were 286, 360 and 1569 respectively. The difference of
      fertilization rates among the three groups was not significant (74.8%, 75.2% vs
      77.5%, P>0.05). No difference was seen in the implantation and clinical pregnancy
      rates of the TESE group from the ejaculation group (29.87% vs 29.54%; 48.15% vs
      52.60%, P>0.05). However the implantation and clinical pregnancy rates were
      higher in the PESA group compared with the TESE and ejaculation groups (50.85% vs
      29.87%, 29.54%; 68% vs 48.15%, 52.60%, P<0.05). In the PESA group, 17 clinical
      pregnancies were achieved including 9 ongoing pregnancies, and 6 live deliveries
      and 2 miscarriages. While in the TESE group, 13 clinical pregnancies were
      achieved including 4 ongoing pregnancies, 7 live deliveries and 2 miscarriages.
      CONCLUSION: ICSI with PESA and TESE is an effective method to treat azoospermia.

PMID- 15562789
TI  - [Quality evaluation of three different sperm counting chambers].
AB  - OBJECTIVE: Semen evaluation is the most important laboratory test for assessing
      male fertility. However, lack of strict quality control (QC) for semen analyses
      in hospital andrology laboratories makes it difficult and meaningless to compare
      semen data between different laboratories. This paper reports a comparative study
      on the accuracy of the Hemacytometer (Qiujing Inc., Shanghai, China), Makler
      (Sefi-Medical Instrument, Haifa, Israel), and Cell-VU (Millennium Sciences Inc.,
      New York, USA) chambers for sperm counting. METHODS: Both low [(18 +/- 2.5) x
      10(6)/ml] and high [(35 +/- 5) x 10(6)/ml] pre-calibrated standard latex bead
      solutions (Hamilton Thorne Biosciences, USA) were used as the quality control
      solution to perform counts on the three different counting chambers. Bead counts
      for the three different chambers were compared, and variability within the
      chambers determined for standard solutions at low and high concentrations of
      latex beads, respectively. RESULTS: Mean bead concentrations for the Cell-VU,
      Hemacytometer and Makler chambers were (37.63 +/- 4.89), (42.74 +/- 4.98) and
      (53.52 +/- 6.67) x 10(6)/ml respectively for a standard solution containing (35
      +/- 5) x 10(6) beads/ml, and (18.22 +/- 1.77), (20.48 +/- 1.56), (24.97 +/- 4.75)
      x 10(6)/ml respectively for a standard solution containing (18 +/- 2.5) x 10(6)
      beads/ml. Mean bead concentrations for the Cell-VU chamber were consistently
      similar and close to the standard pre-calibrated bead solutions, while those for
      both the Hemacytometer and the Makler chambers were significantly overestimated
      (P < 0.001). The average coefficients of variation for the Cell-VU chamber were
      7.51% for a higher concentration of the standard solution containing (36 +/- 5) x
      10(6) beads/ml and 1.22% for a lower concentration of the standard solution
      containing (18 +/- 2.5) x 10(6) beads/ml, while the mean variation rates of the
      Hemacytometer and Makler chambers were 22.11% and 13.78% for a standard solution
      containing (36 +/- 5) x 10(6) beads/ml, and 52.91% and 38.72% for a standard
      solution containing (18 +/- 2.5) x 10(6) beads/ ml, respectively. CONCLUSION:
      Semen analysis is one of the most important tests for male fertility evaluation,
      but the data obtained from commercially available counting chambers may differ
      markedly in accuracy and reliability. Results from this comparative study
      demonstrated that the Cell-VU chamber exhibits significantly more accurate and
      less variable results than those of the Hemacytometer and Makler chambers. To
      ensure the best possible evaluations and accurate diagnoses, we therefore
      recommend that Cell-VU be used as the standard counting chamber for routine semen
      analyses in andrology laboratories.

PMID- 15562790
TI  - [Effects of xinxibao on sperm quality in oligoasthenozoospermic men].
AB  - OBJECTIVE: To evaluate the effects of zinc and selenium on the sperm quality of
      oligoasthenozoospermic men. METHODS: Thirty-four cases of oligoasthenozoospermia
      were treated with Xinxibao (Zinc & Selenium Tablet) three times a day and five
      tablets at a time for ninety days in succession. The seminal routine analysis was
      performed by computer-assisted sperm analysis (CASA) at the end of each month.
      RESULTS: The sperm quality was improved significantly sixty days and ninety days
      after treatment. Five cases (14.7%) showed remarkable effect, 25 (73.5%)
      improved, and 4 (11.8%) did not respond. CONCLUSION: Zinc and selenium can
      significantly improve the sperm quality of oligoasthenozoospermic men.

PMID- 15562791
TI  - [Influence of androgen deprivation therapy on bone mineral density in men with
      prostate cancer].
AB  - OBJECTIVE: To determine the influence of androgen deprivation therapy (ADT) on
      bone mineral density (BMD) in men with prostate cancer. METHODS: Forty-nine men
      with prostate cancer underwent BMD determination and then were classified into
      two groups: non-ADT group (21 cases), who were about to receive ADT, and ADT
      group (28 cases), who had received ADT for more than 1 year. BMD was determined
      by dual energy X-ray absorptiometry (DEXA) in the lumbar spine (L2-4) and femoral
      neck in all the patients. The Age-Matched Z scores were used as the reference
      standard for controlling the difference of age, sex and weight. RESULTS: Thirteen
      (62%) of the non-ADT group and 23 (82%) of the ADT group fulfilled the BMD
      criteria for osteopenia or osteoporosis. Z scores for the Age-Matched control in
      the lumbar spine and femoral neck were -(0.9 +/- 0.7) and -(0.6 +/- 0.5) in the
      non-ADT group, and -(1.8 +/- 1.1) and -(1.6 +/- 1.0) in the ADT group,
      respectively (P<0.01). The men of the ADT group had significantly lower BMD in
      the lumbar spine and femoral neck than those of the non-ADT group. CONCLUSION:
      Pre-existing osteopenia and osteoporosis are common in men with prostate cancer
      before ADT. ADT is significantly associated with the loss of BMD and the
      evaluation of BMD is necessary before ADT for men with prostate cancer.

PMID- 15562792
TI  - [A pilot study of photon therapy for benign prostate hyperplasia (a report of 30
      cases)].
AB  - OBJECTIVE: To investigate the clinical efficacy and safety of photon therapy for
      benign prostate hyperplasia (BPH). METHODS: Thirty patients with severe BPH
      received brachytherapy of prostate photon treatment system irradiation for one
      month, with the active area of the applicator located in the rectum, and at a
      dosage of 726-810 cGy. International prostate symptom score (IPSS), quality of
      life (QOL), volume of prostate gland, maximum flow rate (Qmax), and residual
      urine were evaluated before and after the treatment. RESULTS: After one-month
      treatment, 18 cases remarkably improved, 9 slightly improved and 3 had no
      response. There was significant improvement in IPSS, QOL, volume of prostate
      gland, Qmax and residual urine (P<0.01, except Qmax P = 0.038). CONCLUSION:
      Prostate photon treatment system can be used as a safe, effective, micro
      invasive, convenient and economical therapy for severe BPH, especially applicable
      to older and weaker patients.

PMID- 15562793
TI  - [Diabetic damage to male reproduction and its mechanism].
AB  - Diabetes is a metabolic disease caused by complicated factors, and its damage to
      the male reproductive system is threatening men's health. This article reviews
      the pathophysiological changes in the diabetes-damaged male reproductive system
      and the mechanism of these changes. Oxidative stress induced by hyperglycemia
      plays an important role in working damage to the reproductive system of diabetic
      males, for which some anti-oxidative substances may prove to be an effective
      cure.

PMID- 15562794
TI  - [Psychological factors and male reproductive health].
AB  - Reproductive health is a focus of the 21st century medical sciences. Researches
      on the correlation between psychological factors and male reproductive health may
      help discover the rules of the development of male diseases. This paper analyzes
      the social root-cause of the adverse psychological factors of men, discusses how
      psychological factors affect male reproductive health, and proposes some remedial
      measures for related psychological problems.

PMID- 15562795
TI  - [Congenital absence of the vas deferens].
AB  - Congenital absence of the vas deferens (CAVD) is an important factor that
      contributes to obstructive azoospermia and male infertility. The etiology of CAVD
      is associated with the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene and defects in the Wolffian duct, and frequently complicated by renal
      agenesis and other urogenital abnormalities. Physical examination may reveal
      nonpalpable scrotal vas deferentia, while vasography intrinsic vasal absence.
      Ultrasound and computerized tomography (CT) can rule out the abnormalities of the
      upper urinary tracts and the seminal vesicles. Although it is difficult to cure
      the disease, it is now possible for CAVD patients to father children with the
      help of assisted reproductive technology (ART). The present review is focused on
      the etiology, diagnosis and treatment of CAVD.

PMID- 15562796
TI  - [System review of the Chinese medicine bushenhuoxue for treating benign prostatic
      hyperplasia].
AB  - OBJECTIVE: To make a system review of the effects of Bushenhuoxue (kidney
      tonifying and blood-activating prescription), a category of compound Chinese
      medicines, on benign prostatic hyperplasia (BPH) and its side effects. METHODS:
      All the research articles about Chinese medicines treating BPH from January 1978
      to February 2003 were retrieved using the methods of international evidence-based
      medicine (EBM), and their qualities were evaluated based on JADAD standard and
      concealment of research allocation. Then the included articles went through META
      analysis with Revman 4.2 software. RESULTS: The efficacy of Bushenhuoxue on BPH
      was better than Qianliekang but not statistically different from finasteride. The
      combined use of Bushenhuoxue with surgery had no statistical difference from mere
      surgical treatment. Four articles reported the side effects of this compound
      Chinese medicine including upset and pain in the abdomen, nausea, diarrhea and
      dryness of the nose. CONCLUSION: Massive, multi-center and randomized controlled
      clinical trials should be conducted to find out more effective methods for
      treating BPH with Chinese medicines based on the improvement of measurable
      symptom evaluation method and for evaluating their side effects.

PMID- 15562797
TI  - [Cardiovascular safety of vardenafil].
AB  - Vardenafil is a new type of PDE5 inhibitor (PDE5I) with great inhibiting
      potential on PDE5 (IC50: 0.01 nmol/L) for enhancing erectile function.
      International and domestic clinical studies showed it to be safe and effective in
      treating ED with mild temporary side effects such as headache, dizziness,
      flushing and rhinitis. In this paper we reviewed the cardiovascular safety of
      vardenafil. Studies showed that clinical dosage of vardenafil could decrease the
      systematic arterial blood pressure mildly (< 10 mmHg) , however, it did not
      interact in a potentially hazardous way with antihypertensive or antianginal
      therapy, with the exception of organic nitrates. Vardenafil slightly prolonged
      the QT interval (QTc) in cardiac repolarization, but with no evidence to prove
      that it could cause arrhythmia in clinical studies. The rates and categories of
      cardiovascular adverse events of vardenafil therapy were not significantly
      different from placebo in 5 clinical trials. Present studies demonstrated that
      clinical dosage of vardenafil appeared generally well tolerated in most patients
      with chronic and stable cardiovascular disease and it was an ideal drug for the
      first line treatment of ED.

PMID- 15562798
TI  - [Vardenafil for the treatment of erectile dysfunction in men with diabetes].
AB  - The prevalence of erectile dysfunction (ED) is higher in diabete patients than in
      non-diabete men. Moreover, the treatment of ED is more challenging in men with
      diabetes. Vardenafil, a novel and highly selective phosphodiesterase 5 inhibitor,
      is the first line therapy for the broad ED population. Recent large-scale
      clinical trials indicated that vardenafil improved erectile function in ED men
      with diabetes regardless of the baseline ED severity and plasma HbA1c levels, and
      it was generally well tolerated.

PMID- 15562799
TI  - Germ-line engineering and late-onset diseases: the ethics of self-evolution.
AB  - While some claim that germ-line engineering is a definite possibility, the law in
      Israel and in most countries states that it should be avoided. This paper
      suggests that using GLE in order to 'self-evolve' (when it becomes safe) is not
      only inevitable but also morally justified. This paper argues that, The great
      achievements of healthcare during the last century, enabling longer life, have
      made almost everyone prey to late-onset diseases. The conundrum of healthcare
      allocation is worsening, partly due to late-onset dysfunctional genes that have
      escaped the barriers of natural selection, Trying to free future generations from
      late-onset diseases (such as Alzheimer's for instance) may be considered as
      'eugenics' but, if pursued freely and justly, is a noble goal. We will be
      affecting future generations whether or not we use GLE. By definition, GLE might
      be reversible; it follows therefore that GLE may not necessarily represent the
      dramatic change inserted in the germ line forever--as is usually suggested.
      Reproductive freedom and justice are paramount in this scenario. These values are
      not necessarily incompatible if the right policies are in place.

PMID- 15562800
TI  - Quarantine after an international biological weapons attack: medical and public
      health requirements for containment.
AB  - The world now faces the dreadful possibility of biological weapons attacks by
      terrorists. Healthcare systems would have to cope with such emergencies should
      all preemptive measures fail. Information gained from the Global Mercury exercise
      and the SARS outbreak has shown that containing an outbreak at the start is more
      effective than reacting to it once it has spread and that containment should be
      treated both nationally and internationally. On the national level this entails
      developing rapid and effective methods to detect and identify infected cases, and
      implementing isolation and control measures to lower the risk of further
      transmission of the disease while assuring the safety of medical teams and
      laboratory workers. Strategic contingency plans should incorporate well-defined
      procedures for hospitalization and isolation of patients, providing regional
      backup of medical personnel and equipment and maintaining close cooperation
      between the various bodies in the healthcare system. Quarantine is an effective
      containment measure, especially if voluntarily imposed. Modern communication
      systems can help by sending professional teams timely instructions and providing
      the public with information to reduce panic and stress during quarantine
      procedures. Informing the public poses a dilemma: finding a balance between
      giving advance warning of an imminent epidemic outbreak and ascertaining the
      likelihood of its occurrence. Containment of international bioterrorist attacks
      depends entirely on close international cooperation to implement national and
      international strategic contingency plans with free exchange of information and
      recognition of procedures.

PMID- 15562801
TI  - The professionalism movement.

PMID- 15562802
TI  - Off-pump coronary artery bypass grafting: single center experience with 1,000
      consecutive patients.
AB  - BACKGROUND: Advances in surgical techniques and retractor-stabilizer devices
      allowing access to all coronary segments have resulted in increased interest in
      off-pump coronary artery bypass. The residual motion in the anastomotic site and
      potential hemodynamic derangements, however, render this operation technically
      more demanding. OBJECTIVES: To evaluate the OPCAB experience in a single Israeli
      center. METHODS: Between 2000 and 2003 in our institution, 1,000 patients
      underwent off-pump operations. Patients were grouped by the type of procedure,
      i.e., minimally invasive direct coronary artery bypass or mid-sternotomy OPCAB.
      RESULTS: One hundred MIDCAB operations were performed. Of the 900 OPCAB, 767
      patients received multiple grafts with an average of 2.6 +/- 0.6 grafts per
      patient (range 2-4) and the remaining patients underwent single grafting during
      hybrid or emergency procedures. In the multiple-graft OPCAB group, complete
      revascularization was achieved in 96%. Multiple arterial conduits were used in
      76% of the patients, and total arterial revascularization without aortic
      manipulation, using T-graft (35%) or in situ configurations, was performed in
      61%. The respective rates for early mortality, myocardial infarction and stroke
      in the MIDCAB were 1%, 0% and 2%, and 2%, 1.3% and 0.9% in the multiple-vessel
      OPCAB groups. Multivariate analysis identified renal dysfunction (odds ratio
      11.5, confidence interval 3.02-43.8; P < 0.0001) and emergency operation (OR
      8.74, CL 1.99-38.3; P = 0.004) as predictors of mortality. The proportion of off
      pump procedures increased from 9% prior to the study period to 59%. CONCLUSIONS:
      The use of OPCAB does not compromise the ability to achieve complete myocardial
      revascularization. Our procedure of choice is OPCAB using arterial conduits,
      preferably the 'no-touch' aorta technique.

PMID- 15562803
TI  - Diverse presentations of cardiac rupture following acute myocardial infarction.
AB  - BACKGROUND: Cardiac rupture is a rare but ominous complication of myocardial
      infarction. OBJECTIVES: To study the clinical presentation, medical course,
      outcome and echocardiographic predictors of patients with myocardial rupture.
      METHODS: We evaluated 15 consecutive patients with cardiac rupture during a 4
      year period in our department. The current report explores the presence of
      potential risk factors, timing, relation to the thrombolysis, coronary
      interventions and outcome. RESULTS: The index event in all patients was first ST
      elevation myocardial infarction. In seven patients rupture occurred in the first
      24 hours. Pericardial effusion on admission with a clot was present in three
      patients. Five patients received thrombolytic therapy. Only three patients
      underwent coronary angioplasty, but in one case it was performed late and in two
      patients the culprit artery could not be opened. Six patients reached the
      operating room, of whom three survived. CONCLUSIONS: The lack of early mechanical
      reperfusion in acute myocardial infarction and thrombolytic therapy are risk
      factors for cardiac rupture. Pericardial effusion on admission and evidence of a
      clot are echocardiographic indicators of cardiac rupture and should alert the
      medical team to further assess the possibility of cardiac rupture.

PMID- 15562804
TI  - Endoscopic orbital decompression for Graves' ophthalmopathy.
AB  - BACKGROUND: In patients with Graves' ophthalmopathy, orbital decompression
      surgery is indicated for compressive optic neuropathy, severe corneal exposure,
      or for cosmetic deformity due to proptosis. Traditionally this has been performed
      through a transantral approach, but the associated complication rate is high.
      More recently, endoscopic orbital decompression has been performed successfully
      with significantly fewer postoperative complications. OBJECTIVE: To report our
      experience of endoscopic orbital decompression in patients with severe Graves'
      ophthalmopathy. METHODS: Three patients (five eyes) underwent endoscopic orbital
      decompression for Graves' ophthalmopathy at Soroka Medical Center between the
      years 2000 and 2002. The indications for surgery were compressive optic
      neuropathy in three eyes, severe corneal exposure in one eye, and severe
      proptosis not cosmetically acceptable for the patient in one case. An intranasal
      endoscopic approach with the removal of the medial orbital wall and medial part
      of the floor was performed. RESULTS: In all five eyes an average reduction of 5
      mm in proptosis was achieved. Soon after surgery, visual acuity improved in the
      three cases with compressive optic neuropathy, and exposure keratopathy and
      cosmetic appearance also improved. The diplopia remained unchanged. No
      complications were observed postoperatively. CONCLUSIONS: Endoscopic orbital
      decompression with removal of the medial orbital wall and medial part of the
      floor in the five reported eyes was an effective and safe procedure for treatment
      of severe Graves' ophthalmopathy. A close collaboration between ophthalmologists
      and otorhinolaryngologists skilled in endoscopic sinus surgery is crucial for the
      correct management of these patients.

PMID- 15562805
TI  - Occult constipation: a common cause of recurrent abdominal pain in childhood.
AB  - BACKGROUND: An estimated 10% of all children are subject to recurrent attacks of
      abdominal pain of unknown origin. When no organic cause is found, the working
      diagnosis is usually functional abdominal pain. OBJECTIVES: To investigate the
      possible causative role of occult constipation. METHODS: We defined occult
      constipation as the absence of complaints of constipation on initial medical
      history or of symptoms to indicate the presence of constipation. The diagnosis
      was made by rectal examination and/or plain abdominal X-ray. RESULTS: Occult
      constipation was found to be the cause of RAP in 42.6% of children examined.
      Treatment consisted of paraffin oil and phosphate enema. In 82.84% of cases the
      abdominal pain subsided considerably or disappeared within 2 weeks to 3 months of
      treatment. On telephone interview of the parents at 1-1.5 years after discharge,
      96.5% reported that both the abdominal pain and constipation had subsided or
      disappeared. CONCLUSIONS: Occult constipation can be easily identified and
      treated in a large number of children with RAP who were diagnosed as having
      functional abdominal pain.

PMID- 15562806
TI  - Opinion survey of analgesia for abdominal pain in Israeli emergency departments.
AB  - BACKGROUND: The long-standing and ongoing controversy regarding administration of
      analgesia to patients with acute abdominal pain prior to final diagnosis has not
      yet been resolved, despite considerable research. Consequently, wide variations
      in clinical practice exist. OBJECTIVES: To determine the motives, attitudes and
      practices of emergency physicians, internists and surgeons in Israeli emergency
      departments regarding the administration of analgesia before diagnosis in
      patients with acute abdominal pain. METHODS: Questionnaires were completed by 122
      physicians in 21 EDs throughout Israel and the replies were analyzed. RESULTS:
      Most EDs did not have a clear policy on analgesia for undifferentiated abdominal
      pain, according to 65% of the responders. More internists (75%) than surgeons
      (54%) (P = 0.02) and more emergency physicians (81%) than all other physicians
      (60%) (P = 0.05) held this opinion. Most respondents (64%) supported
      administration of analgesia pre-diagnostically. Support for analgesia was
      significantly stronger among internists (75%) compared to surgeons (52%) (P =
      0.03). Despite this wide support, most respondents (68%) indicated that analgesia
      was rarely or never given prediagnostically and, when it was, more surgeons (58%)
      than other physicians made that decision. Most internists (73%) and all surgeons
      reported that patients receive analgesia only after being examined by surgeons.
      Time allocated to the ED (part or full-time) significantly (P = 0.02) influenced
      decision-making, with 51% of part-time physicians vs. 25% of full-time opposing
      prompt administration of analgesia. Opinions on who should decide were divided
      according to medical specialty, with surgeons and internists almost opposed, as
      well as by physician age and percent of his/her time spent working in the ED.
      More surgeons than internists (P = 0.0005) reported that analgesia sometimes
      interfered with making a diagnosis. Most physicians (90%) stated that opiates
      impede diagnosis to some extent. However, 58% of them supported the
      administration of opiates, more or less frequently. Intramuscular diclofenac was
      the most preferred analgesic, followed by intravenous morphine and pethidine;
      individual preferences extended beyond the list of actually administered drugs.
      CONCLUSIONS: There is no consensus on the administration of analgesia for
      undiagnosed acute abdominal pain in EDs in Israel. Physicians' attitudes are
      influenced by training, experience, and percent of personal time allocated to
      work in the ED.

PMID- 15562807
TI  - Obstructive sleep apnea syndrome: the diagnostic strategy dilemma.
AB  - Obstructive sleep apnea syndrome is a major public health hazard affecting 2-4%
      of the adult population; only 10% of these patients are recognized by healthcare
      providers. In the last decade the number of referrals for polysomnography
      increased threefold in Israel, compared to 12-fold worldwide, and is expected to
      increase even more in the coming years. This constant demand for PSG studies is
      beyond the current capacity of sleep laboratories, thus preventing diagnosis for
      most patients with suspected OSAS. In the current review, we examine problems
      facing decision-makers on how to treat the increasing flood of patients
      presenting with symptoms suggestive of sleep-disordered breathing. We evaluate
      the cost-effectiveness of current technologies for OSA diagnosis, i.e.,
      laboratory versus at-home technologies. We conclude that no current alternative
      exists to the use of PSG for OSA diagnosis. When at-home technologies are
      suggested for OSAS diagnosis, data should be provided on factors influencing its
      cost-effectiveness, e.g., accuracy rates of diagnosis, relative cost of human
      resources, and case-mix of patients tested. Since PSG remains the gold standard
      for diagnosis of OSAS, in Israel resources should be allocated to increasing the
      volume of beds for PSG studies in order to increase access to diagnosis and
      treatment, which in turn provides better quality of life, saves scarce resources
      of the healthcare system, prevents unnecessary accidents and increases workers'
      productivity.

PMID- 15562808
TI  - Cigarette smoke effects on salivary antioxidants and oral cancer--novel concepts.

PMID- 15562809
TI  - Prospects of off-pump coronary bypass surgery--an unsettled issue.

PMID- 15562810
TI  - Recurrent abdominal pain in children: is constipation an issue?

PMID- 15562811
TI  - Management of patients with obstructive sleep apnea: which way to go?

PMID- 15562812
TI  - Bleeding from the ductus parotideus following parotidectomy.

PMID- 15562813
TI  - Brunner's gland hamartoma of the duodenum (Brunneroma).

PMID- 15562814
TI  - Plasmacytoma of the pancreas.

PMID- 15562815
TI  - Giant hemangioma of the adrenal.

PMID- 15562816
TI  - How to best manage a patient with renal artery stenosis?

PMID- 15562817
TI  - Balloon angioplasty for renal atherosclerotic disease: absolutely yes.

PMID- 15562818
TI  - Atherosclerotic renal artery stenosis: there is no obvious reason to dilate.

PMID- 15562819
TI  - Simple imaging technique for fitting a below the knee first-time prosthesis.

PMID- 15562820
TI  - Circulating IGF-1 and its role in cancer: lessons from the IGF-1 gene deletion
      (LID) mouse.
AB  - Recent epidemiological studies have suggested a statistical connection between
      serum IGF-1 levels in the upper quartile of the normal range and the relative
      risk of developing certain cancers. Our studies have focused on mouse models
      where circulating IGF-1 levels are reduced, while tissue expression of IGF-1 is
      normal. These mice show a lower risk for the development of colon and breast
      cancers and metastases when compared with control mice, and lend support to the
      hypothesis that circulating IGF-1 may be linked to cancer cell growth.

PMID- 15562821
TI  - Physiology of the IGF system.
AB  - The insulin-like growth factors (IGFs) comprise a complex regulation system with
      two growth factors, cell-surface receptors, 6 specific high affinity IGF binding
      proteins (IGFBP1-6), IGFBP-proteases, as well as other IGFBP-interacting
      molecules. Although the IGFs and their signalling receptor closely resemble the
      peptide hormone (after which they were named) and its cell receptor; their modus
      operandi is very different from that of traditional peptide hormones. The IGFs
      are not stored within cells of a specific tissue but are present at very high
      levels throughout the body. They circulate at total concentrations approximately
      1000 times higher than that of most peptide hormones and although tissue levels
      are somewhat lower, they are still present in vast excess compared to that
      required for maximal cellular stimulation. These high levels are maintained due
      to their association with the IGFBPs, which dramatically slow their clearance.
      The IGFBPs bind the IGFs with greater affinity than their cell surface receptors,
      enabling them to tightly control tissue activity. The IGFBP proteases modify the
      IGFBPs, lowering the affinity with which they bind IGFs. In the tissues the IGFs
      are important regulators of cell survival, growth, metabolism and differentiated
      function; the complex system confers specificity on these actions.

PMID- 15562822
TI  - Molecular basis of insulin action.
AB  - Insulin signalling at target tissues results in a large array of biological
      responses. These events are essential for normal growth and development, and for
      normal homeostasis of glucose, fat and protein metabolism. Elucidating the
      intracellular events following activation of the insulin receptor and the
      interactions between the insulin and IGF-1 signalling systems has been the main
      focus of a large number of investigators, and for excellent reasons. Improved
      understanding of the signalling pathways involved in insulin action and the
      impact of IGF-1 on these processes could lead to a better understanding of the
      pathophysiology of insulin resistance associated with obesity and type 2 diabetes
      and the identification of key molecules that could lead to newer and more
      effective therapeutic agents for treating these common disorders that are already
      an uprising epidemic of the 21st century. This chapter will summarize our current
      understanding of the molecular basis of insulin action, beginning with outlining
      key elements that constitute the insulin signalling pathways. Then, impairments
      in insulin signalling pathways and new paradigms regarding the molecular basis of
      insulin and IGF-1 resistance will be analysed.

PMID- 15562823
TI  - IGF-1 and insulin as growth hormones.
AB  - IGF-1 generated in the liver is the anabolic effector and linear growth promoting
      hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in
      states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts,
      and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1
      receptor blocking. In a positive way, daily IGF-1 administration to stunted
      patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1
      acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces
      organ and tissue growth; its absence causing organomicria. Insulin shares a
      common ancestry with IGF-1 and with 45% amino acid homology, as well as very
      close relationships in the structure of its receptors and post-receptor cascade,
      also acts as a growth hormone. It has protein anabolic activity and stimulates
      IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with
      hyperinsulinism, with or without pituitary GH, have an accelerated growth rate
      and skeletal maturation; so do babies with macrosomia. Whether the insulin growth
      effect is direct, or mediated by IGF-1 or leptin is controversial.

PMID- 15562824
TI  - Insulin-like growth factors and neoplasia.
AB  - Prospective studies suggest that individuals with circulating levels of insulin
      like growth factor 1 (IGF-1) at the high end of the normal range are at increased
      risk for several common cancers. Further data implicate IGF-1 and hyperinsulinism
      as candidate mediators of the effects of body size on cancer risk and prognosis.
      Ongoing research seeks to confirm these findings, to clarify the underlying
      physiology, and to assess their relevance to patterns of cancer incidence. In
      vivo models have not only provided data consistent with the epidemiological
      observations, but also suggest that IGF-1 signalling stimulates growth of
      established cancers. This has led to the development of novel IGF-I receptor
      targeting therapies which have impressive antineoplastic activity in experimental
      systems.

PMID- 15562825
TI  - Loss of IGF2 imprinting: mechanisms and consequences.
AB  - Although the leading dogma for the origin of the diversity in cancer cell
      subpopulations is based on a stepwise selection and accumulation of genetic
      changes that allow uncontrollable malignant growth, there is an emerging
      understanding that the variability of heritable phenotypes in cancer and cancer
      prone cells may also involve epigenetic mechanisms. This is exemplified by the
      unscheduled activation of the normally repressed maternal IGF2 allele in a wide
      range of human cancers. The notion that this so-called loss of imprinting (LOI)
      provides a proliferative advantage by increasing the levels of the IGF-2 ligand
      available to its receptors is supported by the overgrowth symptoms of neonatal
      mice, which has been genetically manipulated to express Igf2 biallelically.
      Although the mechanisms underlying IGF2 LOI in human cancer remains unknown, it
      is likely to directly or indirectly involve the H19 imprinting control region
      (ICR). This stretch of 2 kb sequence just upstream of the H19 promoter functions
      to block enhancer-Igf2 promoter communications by means of a DNA methylation
      sensitive chromatin insulator. We discuss here the possibility that pathological
      mechanisms leading to IGF2 LOI use different strategies with the neutralization
      of the H19 ICR insulator function as a common denominator.

PMID- 15562826
TI  - Insulin and IGF-1 receptor trafficking and signalling.
AB  - Receptor-mediated endocytosis governs the entry of receptors inside the cells. In
      the case of signalling receptors, e.g. tyrosine kinase receptors, the process is
      ligand-dependent and includes a series of surface events which determines the
      specificity of the internalization process and the activation of distinct signal
      transduction pathways. Tyrosine kinase receptors, e.g. the insulin/IGF-1
      receptors, are initially located outside the internalization gates (the clathrin
      coated pits) and concentrated on thin digitations of the cell surface: the
      microvilli. In the case of the insulin receptor, specific motifs of the beta
      subunit are responsible for anchoring the receptor to microvilli. However, the
      molecular mechanisms by which this motif mediates this anchoring are poorly
      understood and necessitate further studies. In particular, the association of
      insulin receptors with cytoskeletal elements or specific lipidic domains
      concentrated on microvilli (e.g. lipid rafts) are under investigation as these
      interactions may provide the appropriate environment for the transduction of the
      insulin metabolic effects. Upon ligand binding, activated insulin receptors
      complexed to insulin are released from microvilli, segregate in clathrin-coated
      pits and enter the cells. In endosomes, insulin is uncoupled from its receptor
      and recycles back to the cell surface, whereas the hormone is degraded in
      lysosomes thus terminating the wave of signalling. These steps participate in the
      biological activity of the hormone via: (1) a regulation of cell sensitivity to
      the hormone through a fine tuning of the number of surface receptors; (2)
      termination of the signalling by intracellular degradation of the ligands; and
      (3) giving the receptors access to plasma membrane domains and intracellular
      compartments from which distinct signalling pathways originate. Current studies
      are designed to compare the behaviour of IGF-1 receptors to that of insulin
      receptors to establish whether different localization on the plasma membrane,
      trafficking pathways and/or kinetics of signalling might explain the different
      biological activities of these two receptors.

PMID- 15562827
TI  - The mTOR/S6K signalling pathway: the role of the TSC1/2 tumour suppressor complex
      and the proto-oncogene Rheb.
AB  - Gene deletion studies in mice and in Drosophila have shown that the 40S ribosomal
      protein S6 Kinases, dS6K in Drosophila and S6K1 and S6K2 in mice are important
      regulators of cell growth in response to insulin stimulation and nutrition
      availability. Here we chiefly focus on dS6k and S6K1, whose activities are
      regulated by an upstream kinase termed the mammalian target of rapamycin (mTOR,
      or dTOR in Drosophila). Our understanding of the mechanisms regulating the
      mTOR/S6K1-signalling pathway will be fundamental in determining the mechanisms
      which control cell growth in response to insulin signalling. Recent findings from
      this laboratory and others suggests that the tumour suppressor complex made of
      two proteins TSC1/hamartin and TSC2/tuberin, acts as a negative regulator of
      mTOR/S6K1 signalling. Mutations in either TSC1 or TSC2 are genetically linked to
      tuberous sclerosis complex (TSC) syndrome, which can lead to severe pathological
      consequences, including mental retardation, epilepsy and autism, as well as
      cardiac, pulmonary and renal failure. Despite a large number of initial reports
      on the TSC1/TSC2 complex, and the finding that its activity is regulated by
      protein kinase B (PKB), the direct target of the TSC1/TSC2 inhibitory complex was
      unknown until recently. Since TSC2 has a GTPase-activating domain, or GAP-like
      sequence, others and we searched for a small GTP binding protein, which may serve
      as the target of TSC1/TSC2 inhibitory complex. In our case we took advantage of a
      genome wide screen in Drosophila for effectors of cell growth and in parallel
      searched for a small GTPase whose activity is up-regulated in TSC2-deficient
      cells. The identified gene was a member of the Ras family of GTPases termed Ras
      homologue enriched in brain or Rheb. Here we review recent findings demonstrating
      that the TSC1/TSC2 inhibitory complex normally acts on Rheb to mediate mTOR/S6K1
      signalling.

PMID- 15562828
TI  - Structural biology of insulin and IGF-1 receptors.
AB  - The insulin and IGF-1 receptors are members of the superfamily of receptor
      tyrosine kinases (RTKs). Many of these have been implicated in human cancers due
      to amplification, overexpression or somatic mutations of the gene. Congenital
      mutations of the RTKs are implicated in a growing number of inherited syndromes.
      Unlike most RTKs that are single-chain monomeric transmembrane polypeptides, the
      insulin and IGF-1 receptors are dimers made of two extracellular alpha subunits
      and two transmembrane beta subunits containing the tyrosine kinase domain. The
      alpha subunits contain the ligand binding sites, of which at least three
      subdomains have been mapped by photoaffinity cross-linking, alanine-scanning
      mutagenesis or minimized receptor constructs. All RTKs are dimeric or oligomeric
      in the ligand-activated form, a mechanism that allows for transphosphorylation of
      the kinase domains and triggers the signalling cascade. The residues of insulin
      involved in receptor binding have been mapped by alanine-scanning mutagenesis.
      They form at least two major epitopes that partially overlap with the dimer- and
      hexamer-forming surfaces of the insulin molecule, and we propose that insulin is
      using those surfaces to cross-link the receptor alpha subunits. This mechanism
      provides a structural basis for negative cooperativity in binding, and probably
      also operates in the IGF-receptor interaction.

PMID- 15562829
TI  - Genetic blockade of the insulin-like growth factor 1 receptor for human
      malignancy.
AB  - Growth factor receptor signals, including insulin-like growth factor (IGF)-1
      receptor (IGF-1R), are required for carcinogenesis and tumour progression in many
      human malignancies. The concept of targeting specific tumorigenic receptors has
      been validated by successful clinical application of multiple new drugs,
      including trastuzumab and gefitinib. In this paper, we review strategies of the
      genetic blockade of IGF-1/IGF-1R that validate this receptor as a promising
      anticancer target. Adenoviruses efficiently transduce malignant epithelial cells
      in culture and are useful for such target validation and potentially also as
      clinical therapeutics. To block IGF-1R signalling, we constructed adenoviruses
      expressing antisense IGF-1R and two truncated IGF-1R (482 and 950 amino acids
      long, IGF-1R/482st and IGF-1R/950st, respectively) that function as dominant
      negative inhibitors (IGF-1R/dn). The truncated receptors were also cloned into
      tetracycline regulated expression vectors to study the effects of modulating this
      pathway without the use of viral vectors. Blocking for IGF-1R suppressed
      tumorigenicity both in vitro and invivo and effectively blocked both IGF-1 and
      IGF-2-induced activation of Akt-1. IGF-1R/dn expression increased radiation- and
      chemotherapy-induced apoptosis and these combination therapies with chemotherapy
      were very effective against tumours in mice. In an intraperitoneal dissemination
      mouse model, blockade of IGF-IR reduced dissemination and prolonged survival
      times. IGF-1R/482st was more effective than IGF-IR/950st due to its bystander
      effect. These studies confirm the validity of IGF-1R as a therapeutic target and
      genetic blockade as a potential strategy for several malignancies, including
      lung, colon and pancreatic carcinoma.

PMID- 15562830
TI  - IGF-1 and prostate cancer.
AB  - By virtue of their potent proliferative and anti-apoptotic effects, the insulin
      like growth factors (IGFs) have been the subject of long-term scrutiny for their
      role in tumorigenesis. With regard to prostate cancer in particular, IGF-1 has
      been shown to stimulate the proliferation of human prostate epithelial cells in
      culture and to be necessary for normal growth and development of the rat and
      mouse prostate. Epidemiological studies have established a link between high
      circulating serum IGF-1 levels and the risk of later developing advanced prostate
      cancer, and overexpression of IGF-1 in the prostate basal epithelial layer of
      transgenic mice results in prostate adenocarcinoma that is similar to human
      disease. Thus, IGF-1 action appears to be important for prostate cancer
      initiation. On the other hand, decreased IGF action, subsequent to the down
      regulation of IGF-1 receptor expression, is associated with advanced, metastatic
      disease. This decrease in IGF-1 receptor may confer a survival advantage to
      prostate cancer cells that have entered the circulation by making them resistant
      to the differentiative effects of IGF-1 at metastatic sites such as bone. The
      molecular mechanisms that effect IGF-1 receptor down-regulation appear to involve
      novel oncogenic functions of the Wilms' tumour suppressor, as well as novel
      actions of the androgen receptor.

PMID- 15562831
TI  - IGF-1 and breast cancer.
AB  - While there have been significant improvements in breast cancer therapy over the
      last few decades, the fact that metastatic breast cancer remains incurable as
      well as the finding that adjuvant therapy reduces the breast cancer death hazard
      ratio by about 30% only underlines the need for novel therapeutic strategies.
      Currently, there is much interest in 'targeting therapy' for different
      malignancies. The majority of breast cancers harbour the insulin-like growth
      factor (IGF)-1 receptor, and IGF-1 has been found to be one of the most potent
      mitogens to breast cancer cells in vitro. Recent findings that the level of IGF-1
      predicts subsequent risk of breast cancer in premenopausal patients further
      underlines the potential biological importance of this growth factor to the
      disease. While endocrine treatment with anti-oestrogens as well as progestins
      have been found to interact with the IGF system in vivo, the extent of these
      effects on antitumour action remains poorly understood. This paper discusses
      current strategies and results aiming at targeting IGF-1 as therapy for breast
      cancer.

PMID- 15562832
TI  - IGFBPs and cancer.
AB  - The proposed insulin-like growth factor binding protein (IGFBP) superfamily are a
      group of secreted proteins that are structurally, functionally and evolutionarily
      related, and include six IGFBPs and over 10 IGFBP-related proteins. The IGFBPs
      have high affinities for insulin-like growth factors (IGFs), thereby modulating
      the mitogenic, anti-apoptotic and metabolic actions of IGFs. In addition, IGFBPs,
      particularly IGFBP-3, also have IGF-independent, anti-proliferative and pro
      apoptotic functions. The IGFBPs are, in turn, modulated by proteolysis.
      Epidemiological data correlating serum IGF/IGFBP levels with the risk of several
      human cancers suggest a possible protective role for IGFBP-3. In vitro studies
      suggest that the potential protective effects of IGFBP-3 involve both IGF
      dependent and IGF-independent mechanisms. Further studies are necessary to
      demonstrate whether the ability of IGFBPs to inhibit the proliferation of cancer
      cells under in vitro conditions has significant clinical implications.

PMID- 15562833
TI  - The IGF receptor as anticancer treatment target.
AB  - The type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed by many
      tumours and mediates proliferation, motility and apoptosis protection. Tumour
      growth and metastasis can be blocked by agents that inhibit IGF-1R expression or
      function, suggesting the IGF-1R as a promising treatment target. We showed that
      antisense-IGF-1R expression in melanoma cells leads to enhanced radiosensitivity
      and impaired activation of ATM, required for DNA double-strand break repair.
      Antisense and dominant negative strategies also enhance tumour cell
      chemosensitivity, and remarkably, immune protection can be induced by tumour
      cells killed in vivo by IGF-1R-antisense. However, antisense agents cause only
      modest IGF1R down-regulation, and can affect the insulin receptor. Specificity is
      an important issue for development of both kinase inhibitors and molecular
      reagents. Using an array-based screen to identify accessible regions of IGF1R
      mRNA, we designed small interfering RNAs (siRNAs) that induce potent IGF1R gene
      silencing without affecting the insulin receptor. These siRNAs block IGF
      signalling, enhance radio- and chemosensitivity, and show genuine therapeutic
      potential. The clinical efficacy of IGF-1R targeting will be determined by key
      factors including the role of the receptor in established tumours, the potency of
      inhibition achieved in vivo, and the extent to which other signalling pathways
      compensate for IGF-1R loss.

PMID- 15562834
TI  - Nutrition, insulin, IGF-1 metabolism and cancer risk: a summary of
      epidemiological evidence.
AB  - A Western lifestyle--characterized by low physical activity, and high dietary
      intake, animal protein, saturated fats and rapidly digestible carbohydrates--is
      associated with increased risks of many cancers. It has been postulated that, at
      least in part, these increases may be mediated by alterations in the metabolism
      of insulin and insulin-like growth factors (IGFs), related to nutritional
      lifestyle. Insulin regulates energy metabolism and increases the bio-activity of
      IGF-1 by enhancing its synthesis and by decreasing several of its binding
      proteins (IGFBP-1 and 2). Insulin and IGF-1 both stimulate anabolic processes as
      a function of available energy and elementary substrates (e.g. amino acids). The
      anabolic signals by insulin or IGF-1 can promote tumour development by inhibiting
      apoptosis, and by stimulating cell proliferation. Epidemiological evidence is
      accumulating and suggests that the risk of cancers of the colon, pancreas,
      endometrium, breast and prostate are related to circulating levels of insulin,
      IGF-1, or both. Nutritional energy balance, macronutrient composition of the diet
      and physical activity levels appear to be major determinants of IGF-1
      bioactivity.

PMID- 15562835
TI  - Retroactive indexing: the apotheosis of a laboratory bulletin?

PMID- 15562836
TI  - The key that opened the door: 50 years of open heart surgery.

PMID- 15562837
TI  - Reflections on the history of coronary surgery.

PMID- 15562838
TI  - Off-pump bypass surgery: the early experience, 1969-1985.
AB  - This is a review of 733 patients who underwent off-pump bypass surgery of the
      right coronary artery and left anterior descending coronary artery between 1969
      and 1985. Two hundred sixty-four patients underwent single bypass of the left
      anterior descending coronary artery, and 79 patients underwent single bypass of
      the right coronary artery. Both the left anterior descending and right coronary
      arteries were bypassed in 390 patients. In contrast to the present-day use of
      mechanical devices to stabilize the target vessel, a 4-suture surgical technique
      was used for this purpose. This technique, which we illustrate, proved less
      cumbersome and made the graft anastomosis easy to perform. Our early experience
      (1969 through 1972) in operating on 199 patients resulted in an operative
      mortality rate of 4.5% (9/199). From 1973 through 1985, improved patient
      selection and use of the left internal thoracic artery as the conduit of choice
      for bypass of the left anterior descending coronary artery reduced the operative
      mortality rate for 534 patients to 1.3% (7/534). Routine postoperative angiograms
      were not performed; therefore, the graft patency rate is not available. However,
      an ongoing 34-year follow-up study of the 264 patients who underwent a single
      left anterior descending bypass showed the saphenous vein graft to be open in
      64.3% (18/28) patients and the left internal thoracic graft in 92.2% (59/64) of
      patients studied. Seventy-four of the 264 patients in this study were still alive
      in 2003.

PMID- 15562839
TI  - Catheter-based transendocardial delivery of autologous bone-marrow-derived
      mononuclear cells in patients listed for heart transplantation.
AB  - Growing evidence suggests that transplantation of autologous bone-marrow
      mononuclear cells (ABMMNCs) can improve the perfusion and contractile function of
      ischemic myocardium. This procedure could potentially benefit transplant
      candidates awaiting a donor heart. To study the safety and feasibility of ABMMNC
      injection, we performed a prospective, nonrandomized, open-label study in 5 heart
      transplant candidates with severe ischemic heart failure. Each patient underwent
      baseline single-photon emission computed tomography, a ramp treadmill protocol, 2
      dimensional echocardiography, 24-hour Holter monitoring, and signal-averaged
      electrocardiography, which were repeated at 2 and 6 months. Transendocardial
      delivery of ABMMNCs was done with the aid of electromechanical mapping to
      identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 cc
      each. There were no deaths, significant arrhythmias, or other major
      complications. The ABMMNC injection reduced the amount of ischemic myocardium
      (not statistically significant). More important, exercise test results improved
      significantly. Myocardial volume oxygen consumption increased from 10.6 +/- 3
      mL/kg/min (baseline) to 16.3 +/- 7 mL/kg/min (2 months) and 23 +/- 7 mL/kg/min (6
      months) (P = 0.0091). In 4 of the 5 cases, this was such an improvement that the
      patients were no longer eligible for cardiac transplantation. In addition,
      metabolic equivalents improved from 3.03 +/- 0.66 (baseline) to 4.65 +/- 1.99 (2
      months) and 6.5 +/- 2.0 (6 months) (P = 0.0092). In conclusion, ABMMNC injections
      were performed safely and resulted in improved exercise capacity. This technique
      may hold promise as an alternative to medical management in patients with severe
      ischemic heart failure who are ineligible for conventional revascularization.

PMID- 15562840
TI  - Closure of atrial septal defects in children: surgery versus Amplatzer device
      implantation.
AB  - We prospectively compared closure and complication rates in 91 children with
      secundum atrial septal defects: 44 (mean age, 8.1 +/- 4.7 years) were treated
      surgically and 47 (mean age, 10.1 +/- 4.9 years) were treated by percutaneous
      Amplatzer septal occluder Complications were classified as mild, moderate, or
      severe. The closure rate was similar in the 2 groups: 42/44 children (95.5%) in
      the surgical group versus 46/47 patients in the device group (97.5%). Mild
      complications were observed in 17/44 patients in the surgical group vs 2/47 in
      the device group; moderate, 11/44 in the surgical vs 1/47 in the device group;
      and severe, 2/44 in the surgical group vs none in the device group. Blood
      products were administered to 18 patients in the surgical group and to 1 patient
      in the device group (P < 0.001). Transcatheter closure of secundum atrial septal
      defects with the Amplatzer device has the advantage of fewer complications,
      shorter hospitalization, and reduced need of blood products. Nonetheless, the
      surgeon's ability to close any atrial septal defect regardless of its size or
      location remains an important advantage of surgery.

PMID- 15562841
TI  - Coronary artery bypass grafting in patients with dialysis-dependent renal
      failure.
AB  - Myocardial infarction and other cardiovascular events constitute the leading
      causes of death in dialysis-dependent, end-stage renal disease patients. Due to
      growth in the elderly population, the number of uremic patients who need surgical
      revascularization is likely to increase. Whether or not coronary artery bypass
      grafting is safe for patients on long-term dialysis remains a great concern. We
      retrospectively reviewed all cases of elective or urgent isolated coronary artery
      bypass grafting in our hospital, from 1 January 1998 through 31 March 2003, and
      identified 23 consecutive patients with dialysis-dependent renal disease (Group
      D). Twenty-two of them were on hemodialysis, and 1 was on peritoneal dialysis;
      the mean duration of dialysis was 19.2 +/- 22.5 months. We chose 69 matched non
      dialysis patients who underwent bypass grafting in 2001 to serve as our control
      group (ND). Preoperative, operative, and postoperative data on these patients
      were compared. Group D consisted of 14 men and 9 women with a mean age of 63.8 +/
      9.9 years, and the mean number of distal anastomoses was 3.5 +/- 1.2. There were
      no significant differences between the 2 groups in preoperative factors,
      intubation time, intensive care unit stay, major complications, and 30-day
      mortality. However, uremic patients had a greater tendency to bleed, longer
      postoperative hospital stays, and more late deaths. We conclude that under a well
      prepared dialysis program and meticulous perioperative management, coronary
      artery bypass grafting can be performed in dialysis-dependent patients, with
      increased but acceptable perioperative morbidity and mortality risks.

PMID- 15562842
TI  - Transmyocardial laser revascularization as an adjunct to coronary artery bypass
      grafting: a randomized, multicenter study with 4-year follow-up.
AB  - We evaluated transmyocardial laser revascularization (TMLR) with coronary artery
      bypass grafting (CABG) versus CABG alone for severe coronary artery disease
      involving 21 myocardial region unsuited for CABG. At 4 centers, 44 consecutive
      patients were randomized for CABG+TMLR (n = 23) or CABG alone (n = 21). Operative
      and in-hospital mortality and morbidity rates were monitored. Clinical status was
      evaluated at hospital discharge, 1 year, and 4 years. Success was characterized
      by relief of angina and freedom from repeat revascularization and death.
      Preoperatively, 20 patients (47%) were at high risk. The CABG technique, number
      of grafts, and target vessels were similar in both groups. Patients undergoing
      CABG+TMLR received 25 +/- 11 laser channels. Their < or = 30-day mortality was
      13% (3/23) compared with 28% (6/21) after CABG alone (P = 0.21). There were no
      significant intergroup differences in the number of intraoperative or in-hospital
      adverse events. The follow-up period was 50.3 +/- 17.8 months for CABG alone and
      48.1 +/- 16.8 months for CABG+TMLR. Both groups had substantially improved angina
      and functional status at 1 and 4 years, with no significant differences in
      cumulative 4-year mortality. The incidence of repeat revascularization was 24%
      after CABG alone versus none after CABG+TMLR (P < 0.05). The 4-year event-free
      survival rate was 14% versus 39%, respectively (P < 0.064). In conclusion,
      CABG+TMLR appears safe and poses no additional threat for high-risk patients.
      Improved overall success and repeat revascularization rates may be due to better
      perfusion of ischemic areas not amenable to bypass. Further studies are warranted
      to determine whether these trends are indeed significant.

PMID- 15562843
TI  - Is posterior leaflet extension and associated commissurotomy effective in
      rheumatic mitral valve disease? Long-term outcome.
AB  - In this prospective study, the long-term effect of posterior leaflet extension
      with glutaraldehyde-preserved autologous pericardium and associated mitral valve
      commissurotomy was investigated in patients with mixed mitral valve disease of
      rheumatic origin. Mitral commissurotomy and posterior leaflet extension using a
      pericardial patch were performed in 25 patients from 1 January 1994 through 31
      December 1995 for mixed mitral valve disease. Preoperatively, no patient had
      chordal rupture or papillary muscle dysfunction. Four patients had left atrial
      thrombosis. The mean age was 35.7 +/- 15.4 years. Associated procedures were
      tricuspid annuloplasty in 4 patients, aortic annuloplasty in 3, aortic and
      tricuspid annuloplasty in 1, and aortic homograft replacement in 1. There were no
      early deaths. One patient died 2 years after surgery due to noncardiac causes.
      Mitral valve area increased from 1.53 +/- 0.63 cm2 to 2 +/- 0.33 cm2 (P = 0. 09),
      and left atrial diameter decreased from 5.8 +/- 1 cm to 4.86 +/- 1.27 cm (P =
      0.07) after 6.1 +/- 0.7 years (range, 5.5 to 71 years). Mitral insufficiency was
      reduced significantly, from grade 2.65 +/- 0.9 to grade 1.2 +/- 0.9 (P = 0.007).
      Functional capacity improved in all patients (New York Heart Association
      functional class, 3 +/- 0.58 preoperatively vs 1.44 +/- 0.82 postoperatively; P =
      0.001). Three patients required reoperation and valve replacement. This type of
      reconstruction may be a good alternative for patients who are not able to use
      anticoagulant therapy. Long-term results of this technique are acceptable;
      however, the risk of reoperation is an important disadvantage in these young
      patients.

PMID- 15562844
TI  - Long-term results of cusp-level chordal shortening for anterior mitral leaflet
      prolapse.
AB  - The technique and early results of cusp-level chordal shortening for isolated
      anterior mitral leaflet prolapse in rheumatic mitral regurgitation were presented
      by us earlier. Here we present our experience from January 1989 through December
      2000. Two hundred twenty-six patients underwent this procedure. The mean age was
      18 +/- 7.22 years. Preoperatively, 38 (16.8%) patients were in New York Heart
      Association functional class 11, 160 (70.8%) were in class IIl, and 28 (12.4%)
      were in class IV. All patients underwent chordal shortening at the cusp level. In
      addition, 8 patients (3.5%) underwent chordal transfer, and 4 patients (1.8%)
      received neochordae. Two hundred twenty-one (97.8%) patients underwent posterior
      annuloplasty using a C-shaped polytetrafluoroethylene collar. In 85 (37.6%)
      patients, cuspal thinning was also performed. Early mortality was 3.5% (8
      patients). Follow-up ranged from 1 to 144 months (mean, 53.02 +/- 31.10 months)
      and was 94% complete. In 68% of survivors, there was no or trivial mitral
      regurgitation. Ten patients required reoperation. There were 8 late deaths.
      Actuarial survival, mitral regurgitation-free survival, and event-free survival
      were 93.3% +/- 1.7%, 41.8% +/- 8.4%, and 73.6% +/- 6.6%, respectively. Among the
      210 survivors, 159 (75.7%) were in New York Heart Association class I, 26 (12.4%)
      were in class II, 22 (10.5%) were in class III, and 3 (1.4%) were in class IV. We
      conclude that cusp-level chordal shortening for isolated anterior mitral leaflet
      prolapse is an effective procedure for correction of anterior mitral leaflet
      prolapse.

PMID- 15562845
TI  - The predictive value of mitral leaflet motion and thickness index scores on early
      restenosis after mitral balloon valvuloplasty.
AB  - The purpose of this study was to investigate whether there is any association
      between mitral leaflet motion (LMI) and leaflet thickness index (LTI) scores and
      the rate of restenosis 3 months after successful mitral balloon valvuloplasty.
      The study population consisted of 46 patients with symptomatic rheumatic mitral
      stenosis who underwent balloon valvuloplasty (37 women, 9 men; mean age, 36 +/- 9
      years). Two-dimensional and Doppler echocardiography were performed in all
      patients on the day before, immediately after, and 3 months after valvuloplasty.
      The severity of restriction of leaflet motion and the severity of leaflet
      thickening were classified into grades of mild (a score of 0), moderate (a score
      of 1), and severe (a score of 2). Subvalvular disease and commissural involvement
      were homogeneous in all patients. Before and immediately after mitral balloon
      valvuloplasty, there were no significant differences in mitral valve area among
      the groups with different LMI and LTI scores. However, at 3 months after
      valvuloplasty, reduction in mitral valve area was more significant in patients
      who had higher pre-procedural LMI and LTI scores (P < 0.05). The rates of early
      restenosis were 0 with a total score of 0, 14.2% with a total score of 1-2, and
      32% with a total score of 3. In conclusion, quantitative assessment of LMI and
      LTI scores by 2-dimensional echocardiography may be helpful in predicting early
      restenosis after mitral balloon valvuloplasty. Early reduction in mitral valve
      area is significant in patients who have higher total LMI and LTI scores.

PMID- 15562846
TI  - The role of surgical intervention in the management of atrial fibrillation.

PMID- 15562847
TI  - Kugel's artery: an anatomical and angiographic study using a new technique.
AB  - In this study, we tried to resolve the confusion in the literature regarding the
      existence and course of Kugel's artery. With the aid of a new technique, we
      studied 100 human hearts ex vivo by radiography and by direct observation through
      dissection, to demonstrate anatomical and postmortem angiographic findings of
      Kugel's artery. Kugel's artery was found in only 6 hearts out of 100 (6%). It
      originated from the proximal left circumflex artery and ended in the right
      coronary artery in 2 cases; from the right coronary artery and ended in the same
      artery in 2 cases; from the left circumflex artery and ended in the same artery
      in 1 case; and from the right coronary artery through the sinus node artery,
      ending in the left circumflex artery, in 1 case. In all 100 hearts, an
      anastomotic network of small atrial branches was found in the same area (lower
      portion of the interatrial septum), connecting the large vessels indirectly.
      Branches of the sinus node artery in all hearts, and of the atrioventricular node
      artery in 66 hearts, participated in this network. Our procedure showed the
      detailed course of Kugel's artery and its course independent from the
      atrioventricular node artery and from the anastomotic network. In conclusion, in
      all cases an anastomotic network of small atrial branches courses through the
      lower interatrial septum and connects indirectly the proximal and distal ends of
      the larger coronary arteries. Kugel's artery provides an additional direct
      arterial anastomosis in the same area in 6% of the hearts.

PMID- 15562848
TI  - Myocardial Ischemia caused by a coronary anomaly: left circumflex coronary artery
      arising from right sinus of valsalva.
AB  - We present the case of a patient in whom a previously undetected anomalous origin
      of the circumflex coronary artery caused myocardial ischemia and led to positive
      myocardial scintigraphic results. Subsequent coronary angiography showed that the
      left circumflex coronary artery arose from the right coronary ostium-an anomaly
      that has been associated with chest discomfort-without atherosclerotic lesions.
      The peripheral distribution of the left circumflex artery was normal. We describe
      the clinical and angiographic findings in our patient and discuss the
      relationship between coronary artery anomalies and ischemia.

PMID- 15562849
TI  - A casual versus causal relationship in coronary artery anomalies :a question of
      method.

PMID- 15562850
TI  - Novel Left Ventricular Assist System II.
AB  - The pump's outflow connector of the Novel Left Ventricular Assist System I (Novel
      LVAS I) has been redesigned to be sutured to the infrarenal abdominal aorta
      either as a procedure of choice (due to its simplicity) or as an alternative in
      the presence of an unhealthy descending thoracic aorta. The implantation of the
      Novel Left Ventricular Assist System II (Novel LVAS II) requires only a single
      passage of the pump's inflow connector through the diaphragm. Of still greater
      importance, the Novel LVAS II enables a considerably shorter (20- or 22-mm)
      Dacron vascular graft as the outflow connector to the abdominal infrarenal aorta.
      The electrocardiogram-synchronized Novel LVAS II possibly ensures the most
      effective approach to the perfusion of visceral organs and kidneys, while
      avoiding both excessive mechanical stress on the blood and anatomical and
      functional damage to the native left ventricle.

PMID- 15562851
TI  - Hybrid endovascular and off-pump open surgical treatment for synchronous
      aneurysms of the aortic arch, brachiocephalictrunk, and abdominal aorta.
AB  - A 71-year-old patient was admitted for synchronous aneurysms of the aortic arch,
      brachiocephalic trunk, and juxtarenal abdominal aorta involving the iliac
      arteries. The patient first underwent open surgical repair of the juxtarenal
      abdominal aortic aneurysm by means of aorto-bifemoral bypass. Three months later,
      he underwent off-pump surgical repair of the aneurysm of the brachiocephalic
      trunk and bypass grafting from the ascending aorta to the brachiocephalic trunk
      and the left common carotid artery, followed by successful exclusion of the
      aneurysm of the aortic arch by deployment of a Zenith TX1 custom-made endograft,
      inserted through a limb of the aorto-bifemoral graft. Combined endovascular and
      open surgical treatment is an appealing new alternative to open surgical repair
      for complex aortic diseases. Debranching of the aortic arch enables endovascular
      grafting in this area, thereby avoiding cardiopulmonary bypass and circulatory
      arrest. Staged and simultaneous procedures should be considered for the treatment
      of complex aortic diseases even in poor-risk patients; however due to the
      investigative characteristics of these procedures, patient selection and
      postoperative follow-up should be carried out with utmost attention.

PMID- 15562852
TI  - An abdominal left ventricular assist device (ALVAD): perspectives and prospects.
      1974.

PMID- 15562853
TI  - Replacement of a Bjork-Shiley Delrin aortic valve still functioning after 25
      years.
AB  - We report the case of a patient who had undergone implantation of a Bjork-Shiley
      Delrin valve in the aortic position 25 years earlier and who now presented with
      severe mitral stenosis. The patient underwent mitral valve replacement and aortic
      valve re-replacement. We review the justification for prophylactic replacement of
      Bjork-Shiley Delrin heart valves.

PMID- 15562854
TI  - Composite graft endocarditis: repair with a mechanical prosthesis.
AB  - We report the case of a 64-year-old man who developed a mediastinal
      pseudoaneurysm due to severe endocarditis, 2 years after aortic root replacement
      with a prosthetic composite graft containing a mechanical valve. After a short
      period of stabilization and antibiotic therapy, the patient underwent surgery.
      The coronary buttons and the sewing ring of the composite graft were found to be
      detached from the graft and the annulus, respectively. Re-replacement with a
      prosthetic composite graft (Dacron graft with a mechanical valve) by the Cabrol
      procedure was performed. Although the homograft is considered by many surgeons to
      be the best graft for aortic root replacement, the synthetic composite graft can
      also be used to treat composite graft endocarditis successfully. The technical
      aspects of homograft versus synthetic aortic root replacement in patients with
      endocarditis are discussed briefly.

PMID- 15562855
TI  - Large mediastinal teratoma originating from the aortic adventitia.
AB  - Many mediastinal tumors do not cause local symptoms, so they are discovered
      incidentally upon thoracic imaging. We present the case of a patient who had a
      large, mature, cystic, mediastinal teratoma. The primary tumor arose from the
      ascending aortic adventitia and was in a highly unusual location-the medial
      mediastinum. The teratoma, which was diagnosed in our patient on thoracic
      computed tomography for follow-up evaluation of empyema, was resected completely.
      To our knowledge, such a teratoma, arising from the adventitia of the ascending
      aorta in the medial mediastinum, has not previously been reported in the English
      medical literature. We review diagnostic methods and therapeutic approaches to
      such mediastinal tumors. We conclude that surgical resection is the method of
      choice for treating these tumors, because it enables radical therapy and tissue
      diagnosis after extirpation.

PMID- 15562856
TI  - Epicardial mesothelial cyst located over the left anterior descending coronary
      artery.
AB  - We report the 5th case of pericardial cyst found to originate from epicardium. A
      30-year-old woman with a history of rheumatic fever underwent open-heart surgery
      for severe aortic and mitral insufficiency. A cyst located over the left anterior
      descending coronary artery was detected during surgery. Excision of the cyst was
      performed with the patient on cardiopulmonary bypass, to avoid injury to the
      artery. Histologic examination showed the cyst to be lined by a single layer of
      benign mesothelial cells, which was consistent with a diagnosis of epicardial
      mesothelial cyst.

PMID- 15562857
TI  - Mitral valve reoperation through the left atrial appendage in a patient with
      mesocardia.
AB  - We report the case of a patient with mesocardia, mitral restenosis, and mitral
      regurgitation. He had undergone an open mitral valvotomy 4 years earlier and,
      therefore, presented us with a problematic approach to the mitral valve. In such
      cases, access to the mitral valve is almost impossible due to the position of the
      valve, which is more posterior and to the left of a normal valve, and due to
      adhesions from the previous surgery We approached the mitral valve through the
      left atrial appendage and replaced the mitral valve with a mechanical prosthesis.

PMID- 15562858
TI  - Pseudoaneurysm and aortobronchial fistula after aortic coarctation repair by
      patch aortoplasty.
AB  - Pseudoaneurysm and aortobronchial fistula are very rare complications of aortic
      coarctation repair by means of patch aortoplasty, and are usually fatal if not
      treated surgically. A 26-year-old man with recent-onset massive hemoptysis had
      undergone aortic coarctation repair by means of Dacron patch aortoplasty at the
      age of 10 in our hospital. Computed tomography of the chest showed a descending
      aortic pseudoaneurysm. Left heart bypass was used for distal perfusion while the
      patient underwent graft interposition. Lung parenchyma around the fistula was
      repaired, and the patient was discharged after an uneventful postoperative
      course. When hemoptysis occurs in a patient with a history of thoracic aortic
      surgery, aortobronchial fistula should be suspected. Close follow-up is mandatory
      for patients who have undergone coarctation repair.

PMID- 15562859
TI  - Echocardiographic diagnosis of aortic valve papillary fibroelastoma.

PMID- 15562860
TI  - Isolated large right atrial myxoma manifested by syncope.

PMID- 15562861
TI  - Magnetic resonance imaging of a pulmonary autograft in the mitral position.

PMID- 15562862
TI  - A rare consequence of uncorrected atrial septal defect: diffuse pulmonary artery
      aneurysms.

PMID- 15562863
TI  - Resolution of an anastomotic aortic pseudoaneurysm 4 years after endovascular
      treatment.

PMID- 15562864
TI  - A sempiternal chest tube?

PMID- 15562865
TI  - In pursuit of an eponym.

PMID- 15562866
TI  - In pursuit of an eponym.

PMID- 15562867
TI  - The mythology of antioxidant therapy.

PMID- 15562868
TI  - Bovine milk allergenicity.
AB  - OBJECTIVE: To provide updated data on the characteristics (eg, structure,
      function, stability) of the main milk proteins identified as allergens and on the
      characterization of their epitopes. DATA SOURCES: Basic literature and the most
      relevant original recent publications on clinical and epidemiologic aspects of
      milk allergy and the biochemistry and immunochemistry of milk proteins. STUDY
      SELECTION: The expert opinion of the author was used to select the relevant data
      for the review. RESULTS: Most milk proteins, even proteins present at low
      concentrations, are potential allergens. Epitopes on milk proteins are both
      conformational and linear epitopes, widely spread throughout the protein
      molecules. They may be short fragments, located in hydrophobic parts of the
      molecule, that comprise highly conserved sequences responsible for IgE cross
      reactivity with corresponding milk proteins of other mammals, including humans.
      Those sequential epitopes have also been proposed as good markers of persistent
      allergy to milk proteins and may be of particular clinical significance.
      CONCLUSIONS: No specific structure or function is associated with allergenicity
      of milk proteins. Due to the great variability and heterogeneity of the human IgE
      response, no single allergen or particular structure can account for a major part
      of milk allergenicity. Furthermore, the available evidence is not sufficient to
      establish an intake threshold below which allergic reactions are not triggered or
      to predict reliably the effect of food processing on allergenic potential of milk
      proteins.

PMID- 15562869
TI  - Peanut allergenicity.
AB  - OBJECTIVE: To provide the reader with a relevant review of the structure and
      allergenicity of the major peanut allergens, while also exploring predictors of
      clinical reactivity to peanuts, the natural history of peanut allergy, and novel
      therapeutic strategies for peanut hypersensitivity. DATA SOURCES: A PubMed search
      for the years 1980 to 2004 was performed using the following search terms: peanut
      allergy, food allergy, anaphylaxis, peanut allergen structure, and peanut
      immunotherapy. STUDY SELECTION: Articles highlighting major advances in the study
      of peanut allergy were selected for further review. RESULTS: Peanut allergy is
      the most serious of the hypersensitivity reactions to foods due to its
      persistence and high risk of severe anaphylaxis. The major peanut allergens and
      their associated immunodominant IgE-binding epitopes have been characterized.
      Definition of these allergens has lead to an increased understanding of the
      peanut-specific immunologic response and improved predictors of clinical
      reactivity to peanuts. An understanding of these mechanisms is vital for the
      eventual development of safe and effective immunotherapy for peanut allergic
      patients. Novel therapeutic and diagnostic approaches are being developed for
      patients with peanut hypersensitivity. CONCLUSIONS: Improved understanding of the
      molecular structure of the major peanut allergens and the peanut-specific immune
      response has lead to significant diagnostic and therapeutic advances in the study
      of peanut allergy.

PMID- 15562870
TI  - Genetic modification of food allergens.
AB  - OBJECTIVE: To review allergen risk evaluation for genetically modified foods and
      our ability to predict protein allergenicity, methods that are being used to
      develop foods with reduced allergenic activity, and clinical aspects relative to
      assessing potentially allergic patients. DATA SOURCES: Information was identified
      using the MEDLINE database for governmental, international, and industry
      organizations that have considered possible unintended health effects such as
      food allergy and how they can be avoided. DATA SELECTION: The author's knowledge
      of the field was used to select articles for inclusion in this review. RESULTS:
      Organizations have created a decision process that has generally been successful
      in avoiding development of products that cause allergic reactions. Since some
      proteins expressed do not have any history of human exposure, risk evaluation may
      be more of a challenge for them. Biotechnology has also been used to try to
      develop foods with reduced allergenicity, and in future years such products
      should yield safer foods. CONCLUSIONS: Allergy risk evaluation for known
      allergens and genetically modified foods appears to be reasonable and provides
      assurance of food safety. Allergenicity evaluation of novel proteins is a more
      complicated process that needs to be and will be improved as our knowledge of
      food allergens increases. Biotechnology can be used to produce safer and
      healthier foods; for example, allergenicity of some foods may be reduced through
      biotechnology. The role of the health care professional in assessing allergic
      reactions to genetically modified foods is essential and should play a greater
      role in the interaction of consumers, industry, and regulators.

PMID- 15562871
TI  - Gastrointestinal immunopathology and food allergy.
AB  - OBJECTIVE: To review the current data that support the pivotal function of the
      gastrointestinal immune system in health and disease and its critical role in the
      pathogenesis of a wide variety of clinical disorders associated with food allergy
      (FA). DATA SOURCES: Internet-based literature search and our own data. STUDY
      SELECTION: The studies included in this review were selected based on the expert
      opinion of the authors. RESULTS: In contrast to the beneficial expressions of
      gastrointestinal-associated lymphoid tissue, which are seen with relevance to
      newer methods of delivery of vaccines directly applied to the gastrointestinal
      mucosal surfaces (eg, oral poliovirus, rotavirus, Salmonella typhi vaccines), the
      adverse consequences of a mucosal immune response gone astray are evidenced in
      many diseases such as FA. A classification of clinical disorders associated with
      FA based on classic mechanisms of immunologic injury is presented, which includes
      the following: (1) IgE-mediated, (2) non-IgE-mediated, and (3) mixed IgE- and non
      IgE-mediated disorders. Our study of immunologic disturbance in patients with non
      IgE FA revealed a pattern of increased CD4+ and decreased TH1 cell counts in
      peripheral blood mononuclear cells in contrast to patients with celiac disease,
      where a pattern of increased CD8+ and TH1 cell counts in peripheral blood
      mononuclear cells and increased CD8+ cell counts was seen. CONCLUSIONS: The
      gastrointestinal immune response thus plays a pivotal role in maintaining
      protective immunity in health and a critical role in the pathogenesis of a wide
      variety of clinical disorders associated with FA.

PMID- 15562872
TI  - Current and potential uses of probiotics.
AB  - OBJECTIVE: To present data that support the current and potential use of
      probiotics in treating or preventing allergic disorders of the gastrointestinal
      tract and other disorders. DATA SOURCES: Case reports, double-blind studies, and
      animal studies were reviewed. STUDY SELECTION: Studies were selected based on the
      expert opinion of the authors. CONCLUSIONS: Well-designed research studies
      suggest that supplementary consumption of certain probiotic strains may
      temporarily alter the intestinal microflora of infants and children to produce a
      beneficial effect. However, generalization of probiotic effects must not be made
      and critical scientific evaluation must be used in directing patients to select
      the appropriate probiotic.

PMID- 15562873
TI  - Clinical tolerance of processed foods.
AB  - OBJECTIVE: To review the effects of technological processing on selected foods of
      relevance to childhood allergy from the viewpoints of reduced allergenicity,
      contamination of processed foods by allergens introduced during processing, and
      ad hoc technologies to produce reduced hypoallergenic products. DATA SOURCES: We
      searched the literature (PubMed/MEDLINE) for articles published between January
      1994 and April 2004 using the following keywords: food allergy AND process* OR
      heat* OR cooking OR toleran*. STUDY SELECTION: We drew on our collective clinical
      and biological experience to restrict retrieved studies to those of more frequent
      relevance to a hospital allergy practice. RESULTS: Comparatively few clinical
      studies address the modification of allergenicity of food through cooking or
      processing. Dairy foods are largely unaffected by processing and may be
      contaminated by, or themselves become, hidden allergens. Hypoallergenic formulas
      based on milk, soy, or rice and homogenized beef are successful applications of
      allergenicity reduction via technological processing. Egg, fish, condiments, and
      vegetables all carry heat-resistant allergens and should also be considered
      contaminants. Cereals and bakery products are generally well tolerated, but their
      allergenicity may be enhanced by processing; the case of rice is still open.
      Peanut allergens are stable, and the evidence is scant that thermal processing
      affects the allergenicity of soybean and soy hydrolysates. The debate is ongoing
      about the tolerance of vegetable oils. CONCLUSIONS: It is too early to
      systematize clinical studies based on single procedures. Processing affects
      antigenicity, but this does not always translate into safety recommendations.
      Industrial processing is liable to contamination, and monitoring and labeling are
      industry priorities. Clinicians should evaluate foods by as complete a workup as
      possible before recommending processed foods.

PMID- 15562874
TI  - Food allergy in schools: concerns for allergists, pediatricians, parents, and
      school staff.
AB  - OBJECTIVE: To examine the most effective ways to manage allergic reactions in
      schools. DATA SOURCES: The Food Allergy & Anaphylaxis Network Web site and
      federal laws. STUDY SELECTION: The author's expert opinion was used to select
      information for inclusion in this article. RESULTS: Most schools do not have a
      full-time nurse; therefore, school staff should be trained to identify and
      minimize risks and handle a food allergy reaction if one occurs. A delay in
      administration of epinephrine is believed to be a factor in some food allergy
      induced fatal anaphylaxis episodes in schools. All schools should develop a plan
      for recognizing and quickly treating a food allergy reaction. The plan should be
      custom made for each student, with information and guidance from the child's
      physician, and updated as the child matures. The school's policy for handling an
      allergic emergency should be reviewed and practiced regularly so that everyone
      knows what to do as quickly as possible. CONCLUSIONS: Managing food allergies in
      schools requires a team effort among the child's parents, school staff, and the
      child's physician.

PMID- 15562875
TI  - American cockroach.

PMID- 15562876
TI  - Sublingual swallow immunotherapy in the new world.

PMID- 15562877
TI  - Weaving a blanket to protect the entire airway: the goal of comprehensive
      therapy.

PMID- 15562878
TI  - Assessment of asthma control and severity.
AB  - OBJECTIVE: To provide a conceptual framework for defining severity and control in
      asthma, to describe recent advances in measuring asthma control, and to discuss
      the role of severity and control in asthma disease management. DATA SOURCES:
      MEDLINE was searched for relevant English-language articles published between
      1998 and July 2003. Additional sources included key references cited in these
      articles, national and international guidelines for the diagnosis and management
      of asthma, and the author's personal bibliography. STUDY SELECTION: All studies
      that reported on the development and validation of formal measures of asthma
      control, as well as the few editorials that focused on the distinction between
      asthma severity and control, were included. The author's professional judgment
      was used to select for illustrative purposes from among the many purported
      measures of asthma severity in the literature. RESULTS: Although several
      standardized measures of asthma control exist, no direct comparisons of the
      performance and properties of these control measures have been published. The
      available instruments appear more similar than dissimilar. All share the common
      trait of assessing multiple aspects of asthma control, which is believed to
      provide better discrimination than a single measure. CONCLUSIONS: Asthma control
      is different from asthma severity and may be useful as a clinical vital sign for
      patients with asthma. Ultimately, no one measure may be better than any of the
      others or the optimal measure may depend on the intended use of the scale.

PMID- 15562879
TI  - Swollen uvula in an 18-year-old man with hypogammaglobulinemia.

PMID- 15562880
TI  - Canadian trial of sublingual swallow immunotherapy for ragweed
      rhinoconjunctivitis.
AB  - BACKGROUND: Sublingual swallow immunotherapy has been increasingly recognized as
      a safe and efficacious alternative to parenteral specific immunotherapy.
      OBJECTIVE: To determine the safety and efficacy of sublingual swallow
      immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting
      just before and continuing through the ragweed pollen season. METHODS: This
      randomized, double-blind, placebo-controlled study was performed in children and
      adults with a documented history of allergic rhinoconjunctivitis during ragweed
      season at 9 Canadian allergy centers. Active treatment was standardized extract
      of ragweed allergen administered as sublingual swallow drops at increasing doses
      starting shortly before the pollen season and maintenance doses continued daily
      during the season. Primary efficacy variables were symptom and medication scores,
      and secondary variables included global evaluation of efficacy and immunologic
      measurements. RESULTS: Eighty-three patients were included in the safety
      analysis; 76 patients were included in the intent-to-treat analysis. Nine placebo
      recipients and 1 treatment recipient withdrew for lack of efficacy (P = .004).
      Nine patients in the treatment group withdrew because of adverse events, none
      serious (P = .003). Investigator evaluation of efficacy showed that significantly
      more patients improved and fewer deteriorated in the treatment group vs the
      placebo group (P = .047). Ragweed IgE and IgG4 levels increased significantly in
      treatment recipients vs placebo users (P < .001). Sneezing and nasal pruritus
      approached significant improvement in the treatment group vs the placebo group (P
      = .09 and .06, respectively). Quebec City experienced low pollen counts.
      Excluding Quebec City, significant improvement was seen for these 2 symptoms (P =
      .04). CONCLUSION: Sublingual swallow immunotherapy seems to be safe and
      efficacious for ragweed rhinoconjunctivitis even when started immediately before
      the ragweed pollen season.

PMID- 15562882
TI  - Inhalation technique and variables associated with misuse of conventional metered
      dose inhalers and newer dry powder inhalers in experienced adults.
AB  - BACKGROUND: Pressurized metered-dose inhalers (pMDIs) are often poorly used, but
      little information is available concerning use of the newer dry powder inhalers
      (DPIs). OBJECTIVE: To estimate the inhalation technique and variables associated
      with the misuse of pMDIs and newer DPIs in clinical practice. METHODS: A
      multicenter, observational survey was used to evaluate the inhalation technique
      in 1,404 experienced outpatients aged 15 to 88 years affected mostly by asthma
      (47%) and chronic obstructive pulmonary disease (39%). A total of 1,056 patients
      were using pMDIs, 190 in conjunction with a large volume spacer (LVS); regarding
      DPIs, 230 patients were using the Aerolizer Inhaler, 524 were using the
      Turbuhaler, and 475 were using the Diskus. In each center, a trained observer
      recorded patients' inhalation techniques for each inhaler used against a
      standardized step-by-step checklist. RESULTS: Twenty-four percent and 3% of
      patients used pMDIs poorly, alone or with an add-on LVS, respectively. Failure to
      correctly perform essential steps for reliable lung delivery with the Aerolizer
      Inhaler, Turbuhaler, and Diskus was found in 17%, 23%, and 24% of patients,
      respectively. There was no difference in most variables correlated with poor
      inhalation between patients using pMDIs and those using DPIs. CONCLUSIONS: The
      use of DPIs is associated with a similar percentage of inadequate inhalation
      technique as the use of pMDIs in clinical practice. The addition of an LVS to a
      pMDI and education from health care personnel, rather than simply changing
      inhalers, represent the best strategies for minimizing poor inhalation technique.

PMID- 15562881
TI  - Protective effect of montelukast on lower and upper respiratory tract responses
      to short-term cat allergen exposure.
AB  - BACKGROUND: Challenge with short-term exposure to airborne cat allergen in
      sensitized patients produces pulmonary function changes and rhinitis symptoms.
      OBJECTIVE: To determine the benefit of montelukast, 10 mg, for patients with
      concomitant asthma and allergic rhinitis as demonstrated by protection against
      both lower and upper airway responses to cat allergen challenge. METHODS: This
      randomized, crossover study treated patients with montelukast vs placebo during
      two 2-week, double-blind treatment periods, separated by a 1-week washout period.
      After each treatment period, patients underwent a 60-minute or less exposure to
      high levels of airborne cat allergen. Lower and upper airway responses were
      measured by spirometry and symptom scores. RESULTS: Of 52 patients with data from
      both treatment arms, 79% of patients taking montelukast and 67% taking placebo
      were exposed to the full 60-minute allergen challenge. Montelukast provided
      significant (P < or = .001) protection against allergen challenge in the lower
      airway coprimary end point of area under the curve during challenge (AUC0-60min)
      for percentage decrease in forced expiratory volume in 1 second: mean of 10.5%
      per hour and 14.7% per hour for montelukast and placebo, respectively. Although
      the effect on the overall nasal symptoms score (NSS) coprimary end point of AUC0
      60min was not statistically significance (P = .12), nasal congestion during the
      challenge and NSS during recovery showed statistically significant (P = .048)
      protection by montelukast. Additional analyses of simultaneous lower and upper
      airway responses showed that more patients taking montelukast (22, 43%) vs
      placebo (13, 26%) were protected from both asthma and rhinitis (P = .02), with an
      odds ratio of 2.24 (95% CI, 1.16-4.32) in favor of montelukast. CONCLUSIONS:
      Montelukast has a protective effect against both lower and upper airway responses
      during exposure to high levels of cat allergen.

PMID- 15562883
TI  - Respiratory repercussions in adults with a history of infantile bronchiolitis.
AB  - BACKGROUND: Viral bronchiolitis in infancy has been identified in previous
      studies as a potential precursor to the development of lower respiratory tract
      illness in later childhood and beyond. OBJECTIVE: To evaluate the long-term
      respiratory repercussions of acute infantile viral bronchiolitis. METHODS: We
      studied 71 individuals aged 19 to 24 years with a history of a viral
      bronchiolitis in infancy and 32 controls. All participants underwent the
      following evaluation: medical history, forced spirometry, methacholine challenge,
      and skin prick testing. RESULTS: The bronchiolitis group had a higher prevalence
      of respiratory symptoms (P = .03) and bronchial hyperresponsiveness (P = .003)
      than controls. The bronchiolitis group also had a lower peak expiratory flow rate
      (P = .02). Skin prick test responses were similar in both groups. CONCLUSIONS:
      The findings from this study support and extend those from previous studies by
      suggesting that viral bronchiolitis may be a predisposing factor for lower
      respiratorytract problems in young adulthood.

PMID- 15562884
TI  - Addition of ibuprofen to pseudoephedrine and chlorpheniramine in the treatment of
      seasonal allergic rhinitis.
AB  - BACKGROUND: Patients with seasonal allergic rhinitis experience many nasal and
      concomitant nonnasal symptoms. Many patients also experience headaches and facial
      pain, pressure, or discomfort. Standard over-the-counter therapy with
      antihistamines and nasal decongestants often does not completely relieve all
      symptoms associated with allergic rhinitis. OBJECTIVE: To establish the
      contribution of ibuprofen when used with pseudoephedrine and chlorpheniramine, a
      standard over-the-counter regimen, to relieve the symptoms of seasonal allergic
      rhinitis. METHODS: In this 7-day, multicenter, randomized, placebo-controlled,
      double-blind, double-dummy, parallel-group trial, qualified subjects were
      randomly assigned to 1 of 4 treatment groups that received combined
      ibuprofen/pseudoephedrine/chlorpheniramine (200/30/2 mg or 400/60/4 mg), combined
      pseudoephedrine/chlorpheniramine (30/2 mg), or placebo. Therapy began when the
      subject experienced a minimum of moderate allergy-associated pain, and it
      continued 3 times a day for 7 consecutive days. RESULTS: Mean pain intensity
      reduction in both ibuprofen/pseudoephedrine/chlorpheniramine treatment groups was
      40% greater than in the placebo group and 33% greater than in the
      pseudoephedrine/chlorpheniramine treatment group (P < .001). Mean changes from
      baseline in total and nonpain symptom scores for both
      ibuprofen/pseudoephedrine/chlorpheniramine doses were significantly greater than
      for placebo (P < .001) and pseudoephedrine/chlorpheniramine (P < .001-.05) but
      were not different from each other. Ibuprofen enhanced the chlorpheniramine and
      pseudoephedrine effects, resulting in incremental 33% to 34% pain relief and 17%
      to 22% allergy symptom relief compared with pseudoephedrine/chlorpheniramine.
      CONCLUSIONS: In both doses of the triple combination, ibuprofen added to the
      effects of chlorpheniramine and pseudoephedrine, resulting in superior relief of
      pain and all nonpain allergy symptoms compared with
      pseudoephedrine/chlorpheniramine treatment. Furthermore, the superior efficacy of
      the lower dose of the triple combination allowed for a decrease in the incidence
      of adverse effects.

PMID- 15562885
TI  - An evaluation of the ocular drying effects of 2 systemic antihistamines:
      loratadine and cetirizine hydrochloride.
AB  - BACKGROUND: Systemic antihistamines, such as loratadine and cetrizine
      hydrochloride, have proven efficacious in the control of many allergic
      conditions; however, patients complain about their drying effects. OBJECTIVE: To
      investigate the ocular drying effects of loratadine and cetirizine hydrochloride
      in individuals with normal ocular health exposed to a controlled adverse
      environment (CAE). METHODS: Eighteen individuals completed a randomized, double
      masked study. Participants were evaluated in a CAE (a chamber that regulates
      humidity, temperature, airflow, and visual tasking) at baseline and after taking
      10 mg of either loratadine or cetirizine hydrochloride daily for 4 days.
      Keratitis, conjunctival staining, and tear film break-up time (TFBUT) were
      examined before and after a 45-minute CAE exposure. Participant-reported ocular
      discomfort was recorded every 5 minutes during CAE challenge. RESULTS: After 4
      days, use of loratadine yielded a mean increase of 0.75 points (107%) in
      keratitis (P < .001), a mean increase of 1.35 points (133%) in conjunctival
      staining (P < .001), a mean decrease of 1.38 seconds (33.7%) in TFBUT (P < .001),
      and a mean increase of 0.32 points (24.8%) in ocular discomfort (P = .05) vs
      baseline. After 4 days, use of cetirizine hydrochloride yielded a mean increase
      of 0.57 points (60%) in keratitis (P < .001), a mean increase of 0.7 points
      (49.7%) in conjunctival staining (P = .005), and a mean decrease of 0.76 seconds
      (19.6%) in TFBUT (P = .05) vs baseline. Loratadine was shown to induce 93%
      greater conjunctival staining after 4 days of use and CAE exposure vs cetirizine
      hydrochloride (P = .04). CONCLUSIONS: Loratadine and cetirizine hydrochloride
      induced signs and symptoms associated with ocular dryness, including increased
      corneal and conjunctival staining, decreased TFBUT, and increased ocular
      discomfort in healthy individuals. Loratadine induced significantly more
      conjunctival staining than cetirizine hydrochloride.

PMID- 15562886
TI  - Identification of preschool children with asthma from low-income families in Los
      Angeles, CA.
AB  - BACKGROUND: Few studies have addressed asthma screening in the preschool age
      group. Early asthma recognition and intervention in preschool children may reduce
      costs related to unscheduled medical care and missed school and work. OBJECTIVE:
      To facilitate an early recognition and referral process for asthma in a preschool
      education program in Los Angeles, CA. METHODS: We administered a 7-question
      survey to parents and guardians of children aged 12 months to 6 years in the
      prekindergarten program of a large school district in Southern California.
      English and Spanish survey questions addressed health care use, school
      absenteeism, and asthma symptoms. Postsurvey reports to parents recommended
      clinical evaluation of children who had probable asthma. RESULTS: Of the 609
      surveys returned from 8 centers (> or = 80% survey return rate), 12% were
      positive for probable asthma and only 5.4% of these cases had been previously
      diagnosed. Of the 12% found to have a high probability of asthma, 3 independent
      factors were associated with a lower likelihood of prior asthma diagnosis:
      Hispanic descent; Spanish speaking; and medicine use 2 or more times per week for
      symptoms such as cough, chest tightness, trouble breathing, or wheezing. Symptoms
      at play, during the day, and at night were noted in 35% to 44% of the
      preschoolers. Cough was the most frequently reported symptom (71.9%, n = 424).
      CONCLUSIONS: A school-based screening process in an early education program can
      help identify preschool children with a high probability of asthma and offer a
      basis for early recognition and intervention.

PMID- 15562887
TI  - Measuring asthma disparities in Hispanics: adherence to the national guidelines
      for asthma treatment in emergency departments in Puerto Rico.
AB  - BACKGROUND: Puerto Rico has the highest prevalence of asthma in the United
      States. Currently, there are no data on actual care given to asthmatic patients.
      OBJECTIVE: To determine the prevalence of documented adherence to the 1997
      National Asthma Education Prevention Program guidelines regarding care given in
      emergency departments (EDs) in Ponce, Puerto Rico. METHODS: A case series was
      conducted using 6,002 ED records with a physician-based diagnosis of asthma for
      1999 through 2001. RESULTS: A history of asthma attack was documented in 82.0% of
      the cases and in all age groups. In-home beta-agonist use was recorded in only
      5.7% of the medical records. Documentation of previous admissions to the ED and
      the intensive care unit were found in 3.5% and 0.33% of the records,
      respectively. Nocturnal symptoms before the ED visit were found in only 6.4% of
      the records, and asthma treatment at home was found in 39.9%. Accessory muscle
      retraction was documented in 99.1% of the cases, and oxygen saturation was found
      in 23.2%. Treatment with nebulized beta-agonist was found in 72.1% of the
      records, and intravenous or oral corticosteroid use was found in 84.1%. Follow-up
      appointments were detected in 64.8% of the cases, and referrals to specialists
      were given in only 5.3%. Rate ratios between our data and those of other
      researchers indicate that there are geographical differences in compliance with
      the guidelines. CONCLUSION: Of the variables tested, only one had acceptable
      levels of compliance, as evidenced in the patient's records, indicating that
      there are alarming differences in ED evaluation and treatment compared with the
      1997 National Asthma Education Prevention Program guidelines.

PMID- 15562888
TI  - Assessing thymopoiesis in patients with common variable immunodeficiency as
      measured by T-cell receptor excision circles.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is one of the most common
      primary immune deficiencies. The immunologic hallmark of CVID is failure of B
      cell differentiation and impaired secretion of immunoglobulins. However, there is
      mounting evidence of accompanying T-cell dysregulation, which could be due to
      abnormal thymic function because the thymus plays a crucial role in T-cell
      development. Recently, it was shown that the human thymus remains functional well
      into adulthood. Current data show that the level of T-cell receptor excision
      circles (TRECs) correlates well with active thymopoiesis. OBJECTIVE: To determine
      whether thymic dysfunction contributes to the pathogenesis of CVID. METHODS: We
      evaluated 15 patients, aged 19 to 65 years, previously diagnosed as having CVID.
      Genomic DNA was isolated from peripheral blood mononuclear cells of each patient.
      Thymic output was evaluated by measuring coding joint TRECs in the total T-cell
      population using real-time polymerase chain reaction. RESULTS: Results were
      compared with known age-matched reference values. The median TREC level in
      patients with CVID (82,034 copies/microg of DNA) was significantly higher than
      that in the healthy cohort (43,000 copies/microg of DNA) (P < .001). In examining
      the relationship between TREC levels and age, we noted that TREC levels
      significantly declined faster with age in patients with CVID vs the healthy
      cohort. CONCLUSIONS: In these patients, thymic dysregulation may be a factor in
      CVID, with an accelerated rate of TREC loss with age compared with healthy
      adults.

PMID- 15562889
TI  - Role of 90K protein in asthma and TH2-type cytokine expression.
AB  - BACKGROUND: The 90K protein (mac-2 binding protein) is a member of the macrophage
      scavenger receptor cysteine-rich domain superfamily. Although systemic levels of
      90K protein have been correlated with inflammation in many diseases, its role in
      asthma is unknown. OBJECTIVE: To determine whether asthma is associated with
      changes in the local and systemic expression of 90K protein and whether 90K
      protein affects the TH2 cytokine profile that is a hallmark of asthma. METHODS:
      The 90K protein levels were measured in the systemic circulation of 69
      individuals with asthma and 68 controls and in the bronchoalveolar lavage fluid
      of 9 controls and 7 atopic asthmatic patients before and after segmental allergen
      challenge. The effects of 90K protein on interleukin 4 (IL-4), IL-5, IL-13, and
      IL-6 production at protein and transcriptional levels in cultured human
      peripheral blood mononuclear cells were determined. RESULTS: Plasma
      concentrations of 90K protein were higher in asthmatic individuals vs controls (P
      = .002), were higher in the bronchoalveolar lavage fluid of asthmatic patients vs
      controls (P < .01), and increased after segmental allergen challenge in atopic
      asthmatic patients (P < .03). Increasing concentrations of 90K protein resulted
      in significantly reduced IL-4, IL-5, and IL-13 concentrations and increased IL-6
      concentrations in the supernatants of cultured peripheral blood mononuclear cells
      (P < .05). Reverse transcriptase-polymerase chain reaction studies showed
      parallel changes in the transcription of these cytokines. CONCLUSIONS: Local and
      systemic concentrations of 90K protein are increased in asthma. Its inhibitory
      effect on TH2 cytokine transcription suggests that increased 90K protein
      expression is an attempt to limit the ongoing inflammation in asthma.

PMID- 15562890
TI  - Identification of allergens in the venom of the common striped scorpion.
AB  - BACKGROUND: The common striped scorpion, Centruroides vittatus, is endemic to the
      southwestern United States and causes thousands of human stings annually.
      Immediate hypersensitivity reactions to C. vittatus venom have been reported.
      OBJECTIVES: To identify specific IgE in 11 patients with immediate
      hypersensitivity to C. vittatus and to characterize the allergens present in the
      venom. METHODS: Skin testing to dialyzed, filtered venom was performed in 5
      patients. Immunoglobulin E immunoblots to whole milked venom was accomplished
      with serum samples from 8 patients. Enzymatic properties of whole venom were also
      determined. RESULTS: C. vittatus venom was found to contain 150 microg/microL of
      protein. Four of 5 patients tested had positive skin test reactions to the
      purified venom extract, with no late reactions. In all 8 patients, sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis demonstrated multiple proteins, 9 of
      which were identified as allergens on IgE immunoblots, ranging in size from 30 to
      170 kD. Enzymatic activity was found to include phospholipase A, alkaline
      phosphatase, esterase, esterase lipase, and acid phosphatase. CONCLUSIONS: C.
      vittatus envenomation may result in immediate hypersensitivity reactions in
      susceptible individuals. Venom specific IgE can be identified by using skin tests
      and IgE immunoblots. The allergens identified in these patients had molecular
      weights distinct from those of known scorpion neurotoxins. A safe and effective
      skin testing extract can be prepared from dialyzed pure venom and may lead to the
      widespread ability to diagnose C. vittatus venom allergy.

PMID- 15562891
TI  - The E237G polymorphism of the high-affinity IgE receptor beta chain and asthma.
AB  - BACKGROUND: The beta chain of high-affinity IgE receptor (FcepsilonRI beta) has
      been proposed as a candidate gene for asthma and atopic diseases. OBJECTIVES: To
      determine the prevalence of the E237G polymorphism of the FcepsilonRI beta gene
      and to investigate its association with asthma and total IgE levels in 3 Asian
      populations. METHODS: A total of 291 asthmatic patients (141 Chinese, 68 Malay,
      and 82 Indian) and 355 asymptomatic blood donors (157 Chinese, 100 Malay, and 98
      Indian) were recruited. The E237G genotype was determined by allele-specific
      polymerase chain reaction. Total serum IgE level was measured by enzyme-linked
      immunosorbent assay. RESULTS: The G allele was more common in Chinese controls
      (17.9%) than in Malay (11.5%) (P = .05) and Indian (9.2%) (P = .01) controls.
      Genotypes with the G allele were more prevalent in asthmatic patients in the
      Chinese population (odds ratio, 1.97; 95% confidence interval, 1.05-3.77; P =
      .04). CONCLUSIONS: There were interethnic differences in the frequencies of the G
      variant among Chinese, Malay, and Indian populations. The E237G polymorphism of
      FcsRI beta may be a risk factor for asthma in the Chinese population.

PMID- 15562892
TI  - Analysis of recurrences in 322 Tis, T1, or T2 glottic carcinomas treated by
      carbon dioxide laser.
AB  - An endoscopic approach to early glottic carcinoma is considered a sound treatment
      for both previously untreated lesions and selected recurrent lesions. Between
      January 1988 and December 2000, we treated 322 patients by CO2 laser at a single
      institution; 37 had Tis, 191 T1a, 55 T1b, and 39 T2 lesions (mean follow-up, 77
      months; range, 6 to 180 months). Kaplan-Meier curves showed a 5-year overall
      survival rate of 88%, a determinate survival rate of 99%, a disease-free survival
      rate of 81%, a rate of ultimate local control with laser alone of 91%, and a
      laryngeal preservation rate of 97%. Univariate and multivariate analysis showed
      that the only factor that statistically affected endoscopic control was lateral
      extension of the tumor with involvement of the bottom of the ventricle (hazard
      risk ratio, 4.0; 95% confidence interval, 1.71 to 9.35). The 58 recurrences were
      classified according to their location compared with the site of the primary
      tumor as follows: 14 in the same area (group A), 27 in adjacent subsites with
      superficial spreading or multifocal distribution (group B), and 17 in adjacent
      sites by submucosal diffusion to the visceral spaces, cartilaginous framework, or
      extralaryngeal tissues (group C). For each group, we analyzed the rate of
      patients who underwent salvage by endoscopic or open neck procedures and the rate
      of laryngeal preservation. Recurrences in groups A and B were endoscopically
      treated in 86% and 74% of cases, respectively. By contrast, in group C no patient
      was endoscopically cured, and there was a low laryngeal preservation rate (47%).
      The pathways of spread in recurrent carcinoma are therefore the single most
      important factor in predicting its endoscopic curability.

PMID- 15562893
TI  - Serial office-based intralesional injection of cidofovir in adult-onset recurrent
      respiratory papillomatosis.
AB  - Intralesional injection of cidofovir is used in the treatment of recurrent
      respiratory papillomatosis as an adjuvant therapy after microsurgical excision
      and CO2 laser therapy. This is conventionally done in the operating room with the
      patient under general anesthesia. We report our experience with 5 patients with
      adult-onset recurrent respiratory papillomatosis who were treated with
      intralesional injections of cidofovir after recurrence of their papillomatosis.
      These injections were given monthly in the office without the use of general
      anesthesia. Before cidofovir injection, all patients required repeated CO2 laser
      treatments at intervals of less than 5 months. We injected 7.5 mg/mL of cidofovir
      transorally into the papillomas under office telescopic control. These injections
      were given monthly for 3 consecutive months. The patients were then followed up
      for 2 to 10 months after therapy to monitor the size of the papillomas. In all 5
      patients, partial remission of the laryngeal papillomatosis was noted during the
      follow-up period. Their need for repeat microsurgery was delayed, and their vocal
      function improved. Intralesional injection of cidofovir in an office setting
      appears to be safe and effective. It might be more convenient and cost-effective
      than performing the same procedure in the operating room with the patient under
      general anesthesia.

PMID- 15562894
TI  - Flexible bronchoscopic removal of a distal bronchial foreign body with
      cinefluoroscopic guidance.
AB  - A 15-year-old girl presented to the emergency department with cough and bloody
      sputum. A chest radiograph demonstrated a radiopaque foreign body (a tongue stud)
      in the right lower lobe. Rigid and flexible bronchoscopy failed to localize the
      foreign body. Under fluoroscopic guidance, the foreign body was identified in a
      right lower lobe distal bronchus; it could be visualized from a distance with a
      3.5-mm flexible bronchoscope. An endobronchial biopsy forceps was passed through
      the suction port of the bronchoscope, but the view of the foreign body was
      obstructed by the biopsy forceps. The bronchoscope could not be advanced closer
      to the foreign body, because its diameter was greater than that of the bronchus.
      Under cinefluoroscopic guidance, the endobronchial biopsy forceps was then used
      to remove the foreign body. A chest radiograph obtained after removal was normal.
      The patient was discharged home the following day. Removal of distal bronchial
      foreign bodies can be challenging, because the bronchial diameter may preclude
      the advancement of the bronchoscope. Cinefluoroscopy is a relatively safe
      therapeutic adjunct that may avert the need for thoracotomy.

PMID- 15562895
TI  - Effect of acid and pepsin on gene expression in laryngeal fibroblasts.
AB  - The aim of this study was to determine changes that momentary low pH with or
      without pepsin causes in gene expression in laryngeal fibroblasts. Cell cultures
      were established from human false vocal fold (FVF) and postcricoidal (PC)
      mucosae. Using a real-time polymerase chain reaction, we analyzed messenger RNA
      gene expression of growth factors (transforming growth factor beta1, vascular
      endothelial growth factor, fibroblast growth factor 2), matrix metalloproteinases
      (MMP-1, MMP-2), and decorin in normal media, pH 4 media, and pH 5 media with and
      without pepsin. The FVF fibroblast gene expression differed substantially from
      the PC fibroblast gene expression. No significant interaction effects for acid
      and pepsin were found in the FVF culture, but in PC cultures we found a
      significant overexpression interaction effect for vascular endothelial growth
      factor, fibroblast growth factor 2, MMP-1, MMP-2, and decorin. These results
      imply that PC tissue is more sensitive than FVF tissue to the noxious effects of
      gastric contents. Furthermore, there appears to be a synergistic effect for acid
      and pepsin exposure in the posterior larynx.

PMID- 15562896
TI  - Anatomic and functional long-term results of canal wall-down mastoidectomy.
AB  - The objective of this study was to evaluate, over the long-term, the anatomic and
      functional outcome of canal wall-down mastoidectomy performed for chronic otitis
      media with cholesteatoma and chronic otomastoiditis resistant to all conservative
      treatment. The study was made through a retrospective review of 338 cases of
      consecutive primary canal wall-down mastoidectomies performed between 1974 and
      1998. Included were 259 cases with sufficient data. In all cases, functional
      reconstruction was performed at the same time as the mastoidectomy. Demographic
      and clinical data were collected from each file. From the clinical data, the
      surgical techniques, complications, the number of follow-up visits necessary to
      ensure cavity cleanliness, details of care provided over the period 1 to 24 years
      (mean, 7 years) after the operation, and audiometric data from admission and from
      the latest postoperative follow-up were retained. Canal wall-down mastoidectomies
      were followed up an average of 10 times during the first 6 months after
      operation, twice a year over the 6-year period following surgery, and less than
      twice a year beyond the 6-year period. Care was dispensed for meatal stenosis,
      scars, infections, polyps, and beads of cholesteatoma. Surgical revisions were
      performed because of residual or recurrent cholesteatoma in 6.1% of the cases,
      because of perforation of the tympanic membrane in 7.3% of the cases, and to
      improve hearing in 12.2% of the cases. At the last consultation, 1 to 24 years
      after surgery, cavities were found to be dry and self-cleaning in 95% of the
      cases, and still humid, with otorrhea, in 5% of the cases. Over the long-term,
      the hearing threshold remained unchanged in 41.3% of the cases. It was improved
      after surgery by 10 to 19 dB in 15.4% of the cases, by 20 to 29 dB in 11.5% of
      the cases, and by more than 29 dB in 3.8% of the cases. The hearing threshold was
      thus improved or at least remained unchanged in 72.0% of cases. Hearing losses
      occurred in 28% of the cases: by 10 to 19 dB in 11.9%, by 20 to 29 dB in 6.5%,
      and by more than 29 dB in 9.2% of the cases. A sensorineural hearing loss of more
      than 60 dB at all frequencies occurred immediately after the operation in 2 cases
      (0.7%). There was 1 case of facial paralysis (0.3%). Four patients (1.5%)
      complained of persistent vertigo. Canal wall-down mastoidectomy is an adequate
      treatment for chronic otitis with cholesteatoma or chronic otomastoiditis. The
      anatomic and functional results are satisfactory, and the rate of complications
      is acceptably low. A tympanoplasty can be performed simultaneously. Thus, for the
      large majority of patients, only a single intervention is required; however, a
      small minority can benefit from a revision tympanoplasty. In order to obtain
      these results, both the patient and the surgeon should engage in a long-term
      follow-up.

PMID- 15562897
TI  - A new electromyographic definition of laryngeal synkinesis.
AB  - Laryngeal synkinesis involves the misdirected reinnervation of an injured
      recurrent laryngeal nerve to vocal fold abductor and adductor musculature. The
      resultant laryngeal dyscoordination can cause vocal fold immobility and airway
      compromise. Although this entity is sometimes considered in the differential
      diagnosis, it is only demonstrable with laryngeal electromyography (EMG). We
      propose a new EMG definition of synkinesis to assist in its identification during
      workup of vocal fold immobility. A retrospective chart review from 1992 to 1997
      in the Voice Disorders Clinic identified 10 patients with laryngeal synkinesis.
      Five patients had bilateral immobility, and 5 had unilateral immobility.
      Monopolar EMG was performed on all patients. Fine-wire EMG was performed when
      monopolar EMG did not elucidate the cause of the immobility. The EMG studies
      revealed synkinetic reinnervation in all subjects. On the basis of the EMG
      results, 7 of the 10 patients were treated with botulinum toxin to weaken the
      undesired reinnervation. Three of the 7 patients had benefit from this therapy.
      Laryngeal synkinesis should be considered as part of the differential diagnosis
      of vocal fold immobility. Awake laryngeal EMG is the only method to demonstrate
      synkinesis of the larynx. The diagnosis of synkinesis is clinically significant
      in cases of immobility to identify patients who might benefit from botulinum
      toxin therapy. Additionally, the presence of synkinesis in cases of unilateral
      immobility may be a contraindication to laryngeal reinnervation procedures. The
      benefit of botulinum toxin therapy is likely greater in the treatment of
      bilateral as opposed to unilateral immobility.

PMID- 15562898
TI  - Preserved otoacoustic emissions in postparotitis profound unilateral hearing
      loss: a case report.
AB  - We report a case of a profound unilateral sensorineural hearing loss following
      epidemic parotitis, with good response of otoacoustic emissions. The patient was
      a 12-year-old girl who had developed a unilateral hearing impairment 2 weeks
      after the onset of mumps. Pure tone audiometry confirmed a profound left
      sensorineural hearing loss. The affected ear showed an absence of auditory brain
      stem responses, whereas transient evoked otoacoustic emissions and distortion
      product otoacoustic emissions were preserved. Epidemic parotitis virus is likely
      responsible for an impairment of inner hair cells, primary afferent fibers or
      their synapses, or a combination of these areas, and it does not seem to have a
      specific tropism for cochlear outer hair cells. Further follow-up will be
      necessary to differentiate the present case from auditory neuropathy.

PMID- 15562899
TI  - Effect of daily cod liver oil and a multivitamin-mineral supplement with selenium
      on upper respiratory tract pediatric visits by young, inner-city, Latino
      children: randomized pediatric sites.
AB  - We studied the effect of daily supplementation with lemon-flavored cod liver oil
      and a children's multivitamin-mineral supplement containing selenium on the
      number of pediatric visits by young, inner-city, Latino children from late autumn
      of 2002 through early spring of 2003. Two private pediatric offices with similar
      demographics, located 1.1 miles apart in upper Manhattan, New York City, were
      randomized to a supplementation site and a medical records control site. Ninety
      four children (47 at each site), 6 months to 5 years of age, were enrolled. The
      mean age of the supplementation group was 2.03 years (SD, +/- 1.04 years); that
      of the control group was 2.08 years (SD, +/- 1.10 years). Children > or = 1 year
      of age in the supplementation group received 1 teaspoon of lemon-flavored cod
      liver oil per day and one half-tablet of a children's multivitamin-mineral; the
      starting dose was halved for children < 1 year of age. The supplements were given
      from enrollment through May 1, 2003. The primary outcome measure was the number
      of upper respiratory tract pediatric visits during the follow-up/supplementation
      period. The supplementation group had a statistically significant decrease in the
      mean number of upper respiratory tract visits over time (p = .042; r = 0.893; y =
      0.602 - 0.002x); the medical records control group had no change in this
      parameter (p = .999; r = 0.0006; y = 0.259 + 1.43 x 10(-6)x). The supplements
      were well tolerated; per parental report, 70% of children completed the 5- to 6
      month course of cod liver oil. Use of these nutritional supplements was
      acceptable to the inner-city Latino families and their young children, and was
      associated with a decrease in upper respiratory tract pediatric visits over time;
      this approach therefore deserves further research and attention.

PMID- 15562900
TI  - Effect of antimicrobial therapy with amoxicillin and cefprozil on bacterial
      interference and beta-lactamase production in the adenoids.
AB  - To compare the effects on the bacterial flora of the adenoids of antimicrobial
      therapy with amoxicillin or cefprozil, we enrolled in a prospective randomized
      study 60 children scheduled for elective adenoidectomy because of recurrent
      otitis media. They were randomized before surgery into 3 groups of 20 patients
      each: a no-therapy group, and groups with 10 days of either amoxicillin or
      cefprozil therapy. Core adenoid materials were quantitatively cultured for
      aerobic and facultative bacteria. The in vitro ability of alpha-hemolytic
      streptococci (AHS) to inhibit the growth of non-type B Haemophilus influenzae and
      Streptococcus pneumoniae was determined. The number of organisms in adenoids
      obtained from patients treated with either antibiotic was reduced as compared to
      that in adenoids from controls. However, in patients treated with amoxicillin, a
      significant decline in the number of AHS, and an increase (in Staphylococcus
      aureus) or no change in the number of other beta-lactamase-producing bacteria
      (BLPB) was noted. In contrast, in those treated with cefprozil, no change was
      noted in the frequency of recovery of AHS, and the number of BLPB decreased.
      Interfering AHS were more often recovered in patients treated with cefprozil. We
      conclude that the adenoids contain more interfering AHS after therapy with a
      second-generation oral cephalosporin (cefprozil) than after amoxicillin therapy.
      This study suggests a potential beneficial effect of using an antimicrobial that
      selectively spares interfering AHS while inhibiting BLPB.

PMID- 15562901
TI  - Middle ear pressure in patients with dizziness.
AB  - The middle ear pressure was analyzed in 112 patients with dizziness. In 37
      patients with Meniere's disease, the middle ear pressure on the low-pressure side
      was significantly lower, the middle ear pressure difference (between the high and
      low sides) was significantly larger, and the maximum compliance on the low
      compliance side was significantly lower than in normal volunteers. The middle ear
      pressure difference was significantly larger during periods of dizziness or
      recurrent dizziness than at the time of remission. In patients with Meniere's
      disease, a middle ear pressure difference of more than 50 decapascals was
      significantly more common among those with abnormal blood gas levels than among
      those with normal blood gas levels. In 27 patients with cervical vertigo and 15
      patients with vertebrobasilar insufficiency, the middle ear pressure difference
      was also significantly larger than in normal volunteers. These results suggest
      that the middle ear pressure difference might be closely related to dizziness in
      Meniere's disease and less closely related in cervical vertigo or vertebrobasilar
      insufficiency. The middle ear pressure difference might also be related to
      abnormal blood gas levels in patients with dizziness.

PMID- 15562902
TI  - Cochlear implants and health status: a comparison with other hearing-impaired
      patients.
AB  - Eighty-four adult cochlear implant (CI) users were compared with 3 other groups
      of severely to profoundly hearing impaired adults concerning quality of life
      (QOL): 1) 19 CI candidates who were accepted as candidates for implantation, but
      who were not operated on; 2) 16 CI candidates whose impairment was not severe
      enough for implantation; and 3) 60 users of acoustic hearing aids. Generic and
      disease-specific QOL questionnaires were used. The CI group scored significantly
      better than the CI candidates who met the criteria for implantation, but who were
      not operated on, on 2 of 6 categories of a disease-specific QOL measure. The CI
      patients had significantly less anxiety and depression than the unoperated CI
      candidates who met the criteria for implantation. Validation and reliability
      testing of 2 disease-specific QOL measures were performed by factor analyses.

PMID- 15562903
TI  - Audiological characteristics of some affected members of a Dutch DFNA13/COL11A2
      family.
AB  - Members of a Dutch DFNA13/COL11A2 family were evaluated with pure tone
      audiometry, stapedial reflexes, otoacoustic emissions, loudness scaling,
      difference limen for frequency, gap detection, and speech perception in quiet and
      noise. The tone audiometry showed a predominant loss for the low and middle
      frequencies, with only a few otoacoustic emissions at thresholds better than 25
      dB hearing level. The stapedial reflexes appeared elevated, and loudness growth
      curves were shifted parallel to those for normal-hearing subjects, indicating a
      shift of the dynamic range toward higher presentation levels. The data for the
      difference limen for frequency, gap detection, and speech perception in noise
      fell within the (near-)normal range. Despite elevated thresholds, all
      suprathreshold functions showed fairly normal properties, suggesting an
      attenuation of signal energy in the cochlea with limited degradation of the
      cochlea's signal analyzing capabilities. The effect of DFNA13/COL11A2 may thus be
      characterized as a cochlear conductive loss.

PMID- 15562904
TI  - Elevated expression of cyclooxygenase-2 in adenocarcinoma of the parotid gland:
      insights into malignant transformation of pleomorphic adenoma.
AB  - Pleomorphic adenoma, the most common type of tumor of the parotid gland, may
      transform into a malignant tumor. In the current study, we investigated whether
      the expression of cyclooxygenase-2 (COX-2) is elevated in adenocarcinoma as
      compared to pleomorphic adenoma. Ten pleomorphic adenomas and 10 adenocarcinomas
      were examined. The tumor specimens were immunohistochemically stained with
      antibodies against COX-2 and Ki-67. The labeling indices of COX-2 in pleomorphic
      adenoma and adenocarcinoma were 6.0% +/- 4.1% and 16.1% +/- 4.6%, respectively,
      and those of Ki-67 in pleomorphic adenoma and adenocarcinoma were 0.77% +/- 0.62%
      and 6.9% +/- 6.6%, respectively. The labeling indices of both COX-2 and Ki-67
      were significantly greater (p < .001) in adenocarcinoma than in pleomorphic
      adenoma. Together with the biological effects of COX-2, these results suggest
      that overexpression of COX-2 plays a crucial role in the pathogenesis of
      malignant transformation of pleomorphic adenoma in the parotid gland.

PMID- 15562905
TI  - New approach for implantable hearing aids: a feasibility study.
AB  - The objective of this study was to test the feasibility of a new kind of
      implantable hearing device based on a cerebrospinal fluid hydroacoustic pathway
      by which sound waves are conducted from the dura mater to the inner ear by
      cerebrospinal fluid. In this prospective animal study, a piezoelectric bimorph
      was implanted into 2 guinea pigs and 1 dog between the skull bone and the dura at
      the parietal area. The bimorph was connected transdermally by wires to a click
      generator. The auditory brain stem response was recorded after stimulation of the
      piezoelectric device by the click generator. In the 3 animals, the auditory brain
      stem response could be recorded in response to a stimulus intensity of 135 dB
      peak equivalent (pe) sound pressure level (SPL; instrument setting),
      corresponding to 3.8 V activating the device. The auditory brain stem response
      disappeared during white noise masking, proving that the origin of the response
      was in the inner ear. The threshold was 125 and 115 dB pe SPL in the 2 guinea
      pigs and 135 dB pe SPL in the dog (instrument setting). We conclude that
      transmission of sound waves by a cerebrospinal fluid hydroacoustic pathway to the
      inner ear is possible. Such a device would have advantages over more traditional
      implantable hearing devices: it would not be necessary to couple it to the
      ossicular chain, and it could be used in patients with infected middle ears.

PMID- 15562906
TI  - Analysis of antigens targeted by circulating IgG and IgA antibodies in patients
      with mucous membrane pemphigoid predominantly affecting the oral cavity.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) includes a range of variants
      frequently having oral, particularly gingival, lesions. It has been suggested
      that MMP exclusively involving the oral cavity could be a distinct subset, but
      the immunological status of patients with predominantly oral lesions has received
      little attention. METHODS: Indirect immunofluorescence (IIF) on normal human skin
      and normal human salt-split skin (SSS) as a substrate and immunoblotting on
      extracts of human keratinocyte cultures and normal human skin were carried out in
      28 consecutive patients with MMP predominantly affecting the gingiva. RESULTS:
      There was no significant difference between frequency of positive SSS-IIF among
      patients with exclusive oral lesions (42%) and with MMP not restricted to the
      oral cavity (78%) (P = 0.114). By immunoblotting, IgG of 13 sera (46%) reacted
      with the 180 kD bullous pemphigoid antigen (BPAg2), six (21%) reacted with the
      230 kD bullous pemphigoid antigen (BPAg1), and two (7%) reacted with an antigen
      of 200 kD. IgA of three sera (11%) reacted with BPAg2 and three (11%) reacted
      with BPAg1. There was no significant difference between frequency of positive
      immunoblotting among patients with exclusive oral lesions (68%) and with MMP not
      restricted to the oral cavity (67%) (P = 1.00). CONCLUSIONS: Most of the MMP sera
      contain IgG and IgA antibodies to the two major bullous pemphigoid antigens,
      independent of clinical presentation. Thus, in the majority of cases, patients
      with exclusively gingival pemphigoid lesions do not appear to have a distinct
      variety of mucous membrane pemphigoid.

PMID- 15562907
TI  - Clinical evaluation of demineralized freeze-dried bone allograft and enamel
      matrix derivative versus enamel matrix derivative alone for the treatment of
      periodontal osseous defects in humans.
AB  - BACKGROUND: A recent study suggests that the addition of enamel matrix derivative
      to demineralized freeze-dried bone allograft may enhance osseoinduction. The
      purpose of this study was to evaluate the use of demineralized freeze-dried bone
      allograft (DFDBA) in combination with enamel matrix derivative (EMD + DFDBA)
      compared to enamel matrix derivative (EMD) alone in the treatment of human
      intrabony periodontal defects. METHODS: Forty patients with a total of 67 sites
      (intrabony defect > or = 3 mm deep) were selected to participate in this single
      masked, parallel design, randomized, controlled clinical trial. Each subject
      received either EMD alone (34 sites) or in combination with DFDBA (33 sites).
      Soft tissue measurements included probing depth (PD), clinical attachment level
      (CAL), and recession. Hard tissue measurements included defect depth, alveolar
      crestal resorption, and defect morphology. Following 6 months of healing, all
      soft tissue measurements were repeated. Forty-nine sites (EMD + DFDBA = 26 sites,
      EMD alone = 23 sites) were surgically reentered. Statistical analyses were
      performed using unpaired and paired Student t tests. RESULTS: Analyses showed a
      significant improvement in soft tissue parameters for both treatment groups (P <
      0.001) as compared to preoperative measurements. There were no statistical
      differences between treatment groups. The probing depth reduction (PDR) for the
      EMD + DFDBA was 3.6 +/- 0.2 mm, while the EMD alone had a PDR of 4.0 +/- 0.3 mm.
      The CAL gain for the EMD + DFDBA group was 3.0 +/- 0.3 mm and 3.2 +/- 0.3 mm for
      the EMD alone group. The mean value for bone fill in the EMD + DFDBA group was
      3.7 +/- 0.2 mm (74.9%), while the EMD alone group demonstrated a mean bone fill
      of 2.6 +/- 0.4 mm (55.3%). While there were no significant differences between
      the two treatments with regards to soft tissue measurements, the combination of
      EMD + DFDBA therapy yielded statistically significant improvements in bone fill,
      crestal resorption, and percentage of sites gaining greater than 50% and 90% bone
      fill when compared to EMD alone (P < 0.001). CONCLUSION: The results of this
      study indicate that there may be an enhancement of hard tissue parameters when
      enamel matrix derivative is added to demineralized freeze-dried bone allograft.

PMID- 15562908
TI  - Effects of intravenous midazolam and diazepam on patient response, percentage of
      oxygen saturation, and hemodynamic factors during periodontal surgery.
AB  - BACKGROUND: The purpose of this double-masked study was to evaluate effects of
      intravenous sedation (IVS) using midazolam or diazepam during periodontal
      procedures on patient recall, psychomotor response, oxygen saturation, and
      hemodynamic factors. METHODS: Seventeen patients received either two or three
      scheduled periodontal surgeries under IVS with midazolam, diazepam, or placebo
      control. Patients were monitored throughout the procedure for hemodynamic
      variables, percent oxygen saturation, level of recall of common objects presented
      at baseline, and psychomotor function via the perceptual speed test (PST).
      RESULTS: Fifteen patients completed the study with average titrated dosages of
      3.3 and 12.1 mg for midazolam and diazepam, respectively. Within the limitations
      of the study, there were few differences observed between the drugs with regard
      to hemodynamic variables, oxygen saturation, and overall percentage of objects
      recalled by patients sedated with either drug. However, midazolam was found to
      cause a greater incidence of amnesia lasting up to 30 minutes when compared to
      placebo. Patients on diazepam required an average of 15 minutes longer to recover
      accuracy as measured by the PST. CONCLUSIONS: The results suggest that diazepam
      and midazolam each may have advantages for IVS. In procedures lasting over 45
      minutes, diazepam appears to be more clinically advantageous including a wider
      margin of safety during titration and gradual recovery. Midazolam may be used for
      shorter procedures for faster onset of action, predictable amnesic effects, and
      relatively rapid recovery.

PMID- 15562909
TI  - Efficacy of antibiotics against periodontopathogenic bacteria within epithelial
      cells: an in vitro study.
AB  - BACKGROUND: Periodontopathogenic bacteria can invade and survive within
      epithelial cells, but susceptibility of intracellular infection to antibiotics
      used in periodontitis treatment has not been studied to date. METHODS: KB cells
      were infected by Actinobacillus actinomycetemcomitans, strain NCTC 9710;
      Porphyromonas gingivalis, strains ATCC 33277 and JH16-1; or Streptococcus
      constellatus, strain J012b. After 2, 4, and 12 hours the bactericidal effect of
      antibiotics (clindamycin, doxycycline, metronidazole, and moxifloxacin) on
      intracellular microorganisms was tested at a concentration up to the 100-fold
      minimum inhibitory concentration (MIC) determined separately on planktonic
      bacteria. RESULTS: The P. gingivalis strains differed in their invasiveness and
      ATCC 33277 was 100-fold more invasive than JH16-1. Doxycycline and clindamycin at
      a concentration 10-fold MIC had no effect, but P. gingivalis intercellular
      infection was significantly reduced by metronidazole at 10-fold MIC after 2 and 4
      hours. Moxifloxacin was effective, but a 100-fold MIC concentration was necessary
      to reduce P. gingivalis strains intracellular growth to 7% of the control. Other
      bacterial species grown inside the KB cells were more susceptible to antibiotics.
      Clindamycin at 10-fold MIC reduced the number of intracellular S. constellatus
      after 4 and 12 hours. This bacterium was eliminated by moxifloxacin at 50-fold
      MIC. Intracellular A. actinomycetemcomitans was killed by 10-fold MIC of
      doxycycline and moxifloxacin after 4 hours incubation. CONCLUSIONS: Moxifloxacin
      was the most efficient antibiotic to treat intracellular infection. However,
      taking into account the MIC values and the levels of antibiotics in gingival
      fluid, elimination of intracellular bacteria by antibiotics alone seems to be
      questionable.

PMID- 15562910
TI  - Effect of the interleukin-1 genotype on outcomes of regenerative periodontal
      therapy with bone replacement grafts.
AB  - BACKGROUND: Previous studies have shown an association between a specific
      genotype for the inflammatory cytokine interleukin (IL)-1 and the severity of
      periodontal disease. The purpose of this study was to evaluate the effect of the
      IL-1 genotype on the outcomes of periodontal surgical regenerative treatment with
      bone replacement grafts. METHODS: Forty-four patients with interproximal
      intrabony defects were treated with bone replacement grafts. Probing depths (PD)
      and clinical attachment levels (CAL) were measured before treatment and at least
      9 months post-treatment. Whole-mouth plaque index (WMPI) and bleeding index
      (WMBI) were recorded as well. All patients were tested for the IL-1 genotype.
      RESULTS: Thirteen (29.55%) of the patients were IL-1 genotype positive. There was
      no statistically significant difference between the genotype-positive and
      genotype-negative groups regarding age, smoking status, gender, WMPI, and WMBI.
      There was no significant difference in PD or CAL between the genotype-positive
      and genotype-negative groups at baseline. Genotype-positive patients had a
      smaller reduction in probing depth (1.86 mm versus 2.13 mm) and a greater gain of
      clinical attachment (1.20 mm versus 0.65 mm). These differences were not
      statistically significant (P = 0.70, P = 0.40). Multivariate regression analysis
      showed that presurgical PD significantly influenced post-surgical PD and CAL, and
      only WMPI significantly influenced CAL. CONCLUSION: In this study, there was no
      evidence that the IL-1 genotype influences the clinical treatment outcomes of
      regenerative periodontal therapy with bone replacement grafts.

PMID- 15562911
TI  - Killing of periodontopathogenic bacteria by photodynamic therapy.
AB  - BACKGROUND: The aim of this study was to evaluate a new approach for killing
      periodontopathogenic bacteria using photodynamic therapy (PDT). METHODS: In this
      study, we investigated the photosensitizers chlorin e6, BLC 1010, and BLC 1014 by
      three different methods for their effect in PDT on the viability of
      periodontopathogenic bacterial species. The methods included examination of
      inhibition zones on agar plates, determination of colony-forming units (CFU), and
      the use of a bacterial viability kit. RESULTS: Using the CFU method, we were able
      to demonstrate that the anaerobic bacteria Porphyromonas gingivalis,
      Fusobacterium nucleatum, and Capnocytophaga gingivalis can be photoinactivated
      completely by illumination with an intensity of 5.3 J/cm2 in the presence of 10
      microM chlorin e6 and 10 microM BLC 1010. With the photosensitizers chlorin e6
      and BLC 1010, we were able to induce zones of inhibition on agar plates. BLC 1014
      failed to produce a zone of inhibition. The results of the bacterial viability
      test also showed that the photosensitizer BLC 1014 provides the lowest
      photodynamic effect in comparison to the others. CONCLUSION: The data collected
      to date suggest that photodynamic therapy with chlorin e6 and BLC 1010 is
      advantageous for suppressing periodontopathogenic bacteria.

PMID- 15562912
TI  - A 6-month comparative clinical study of a conventional and a new surgical
      approach for root coverage with acellular dermal matrix.
AB  - BACKGROUND: The acellular dermal matrix graft (ADMG) has become widely used in
      periodontal surgeries as a substitute for the subepithelial connective tissue
      graft (SCTG). These grafts exhibit different healing processes due to their
      distinct cellular and vascular structures. Therefore the surgical technique
      primarily developed for the autograft may not be adequate for the allograft. This
      study compared the clinical results of two surgical techniques--the
      "conventional" and a modified procedure--for the treatment of localized gingival
      recessions with the ADMG. METHODS: A total of 32 bilateral Miller Class I or II
      gingival recessions were selected and randomly assigned to test and control
      groups. The control group received the SCTG and the test group the modified
      surgical technique. Probing depth (PD), relative clinical attachment level
      (RCAL), gingival recession (GR), and width of keratinized tissue (KT) were
      measured 2 weeks prior to surgery and 6 months post-surgery. RESULTS: Both
      procedures improved all the evaluated parameters after 6 months. Comparisons
      between the groups by Mann-Whitney rank sum test revealed no statistically
      significant differences in terms of CAL gain, PD reduction, and increase in KT
      from baseline to 6-month evaluation. However, there was a statistically
      significant greater reduction of GR favoring the modified technique (P = 0.002).
      The percentage of root coverage was 79% for the test group and 63.9% for the
      control group. CONCLUSION: We conclude that the modified technique is more
      suitable for root coverage procedures with the ADMG since it had statistically
      significant better clinical results compared to the traditional technique.

PMID- 15562913
TI  - Enamel matrix derivative and guided tissue regeneration in the treatment of
      dehiscence-type defects: a histomorphometric study in dogs.
AB  - BACKGROUND: The goal of this investigation was to histologically and
      histometrically evaluate the healing process of dehiscence-type defects treated
      by enamel matrix derivative (EMD) and/or guided tissue regeneration (GTR).
      METHODS: Seven mongrel dogs were used. Buccal osseous dehiscences were surgically
      created on the mesial roots of the mandibular third and fourth premolars. The
      defects were exposed to plaque accumulation for 3 months. After this period, the
      defects were randomly assigned to one of the treatments: open flap debridement
      (OFD), enamel matrix derivative (EMD), GTR with bioabsorbable membrane (GTR), and
      the combination of both procedures (EMD + GTR). After 4 months of healing, the
      dogs were sacrificed and the blocks were processed. The histometric parameters
      evaluated included gingival recession, epithelial length, connective tissue
      adaptation, new cementum, and new bone. RESULTS: A superior length of new
      cementum was observed in the sites treated by EMD (3.7 mm) and EMD + GTR (3.8 mm)
      in comparison with OFD (2.4 mm) (P < 0.05). No statistically significant
      differences were found in the remaining histometric parameters. CONCLUSIONS:
      Within the limits of this study, it can be concluded that EMD alone or in
      combination with GTR barriers may effectively promote new cementum formation. The
      combination of both therapies may not provide additional benefits.

PMID- 15562914
TI  - Effect of recombinant human bone morphogenetic protein-4 dose on bone formation
      in a rat calvarial defect model.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) are being evaluated for
      periodontal and bone regenerative therapy. The objective of this study was to
      evaluate the effect of recombinant human bone morphogenetic protein-4 (rhBMP-4)
      dose on local bone formation in a rat calvaria defect model. METHODS: Calvarial,
      8 mm diameter, critical-size osteotomy defects were created in 140 male Sprague
      Dawley rats. Seven groups of 20 animals each received either 1) rhBMP-4 (2.5
      microg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP-4 (5
      microg)/ACS, 3) rhBMP-4 (2.5 microg) in a beta-tricalcium phosphate (beta-TCP)
      carrier, 4) rhBMP-4 (5 microg)/beta-TCP, 5) ACS or 6) beta-TCP carrier controls,
      or 7) a sham-surgery control, and were evaluated by histologic and histometric
      parameters following a 2- or 8-week healing interval (10 animals/group/healing
      interval). RESULTS: Surgical implantation of rhBMP-4/ACS and rhBMP-4/beta-TCP
      resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose
      range examined, rhBMP-4 did not exhibit an appreciable dose-dependent response.
      Defect closure was not significantly different between the rhBMP-4/ACS and rhBMP
      4/beta-TCP groups. New bone area of the rhBMP-4/ beta-TCP group was significantly
      greater than that of the rhBMP-4/ ACS group; however, bone density in the rhBMP
      4/ACS group was significantly greater than that in the rhBMP-4/beta-TCP group at
      8 weeks (P < 0.05). CONCLUSIONS: rhBMP-4 combined with ACS or beta-TCP has a
      significant potential to induce bone formation in the rat calvaria defect model.
      Within the selected rhBMP-4 dose range and observation interval, there appeared
      to be no meaningful differences in bone formation.

PMID- 15562915
TI  - The relationship between Porphyromonas gingivalis infection and local and
      systemic factors in children.
AB  - BACKGROUND: Porphyromonas gingivalis (P. gingivalis) is a major pathogen related
      to periodontitis. There are few reports on the prevalence and effect of P.
      gingivalis in children. The purpose of the present study was to describe in
      children the level of DNA-P gingivalis in subgingival plaque and the IgG serum
      reactivity to P. gingivalis (IgG-Pg), and examine their relationship to
      demographic, systemic, and oral variables. METHODS: Thirty-four children, aged
      1.83 to 13.42 years, were included in the study; 16 with no systemic disease and
      18 with systemic conditions. The demographic data for caries incidence, plaque
      and gingival indices, probing depth, and alveolar bone height were recorded. The
      IgG-Pg and DNA-Pg levels were determined by enzyme-linked immunosorbent assay and
      DNA-DNA hybridization, respectively. The relationships between the IgG-Pg and DNA
      Pg values to the demographics, oral parameters, and systemic conditions were
      examined. RESULTS: IgG-Pg was evident in 53% of the children and DNA-Pg in 47%.
      IgG-Pg values significantly correlated positively with age, plaque index, and
      bone height. DNA-Pg values had statistically significant positive correlations
      with age. IgG-Pg and DNA-Pg values correlated with probing depth among children
      with systemic diseases. Neither the IgG-Pg nor the DNA-Pg values had a
      significant correlation to systemic conditions. Multiple regression analyses
      indicated that only age remained significantly related to IgG-Pg and DNA-Pg
      values. CONCLUSIONS: P. gingivalis can be found in significant levels in the
      plaque of young children and elicits an immune reaction that increases with age
      and may be related to incipient signs of periodontal disease. Plaque DNA-Pg and
      serum IgG-Pg levels correlate significantly.

PMID- 15562916
TI  - Gingival recession: epidemiology and risk indicators in a representative urban
      Brazilian population.
AB  - BACKGROUND: Gingival recession is a common manifestation of periodontal disease,
      but it is also associated with other risk factors. A few studies have
      investigated the epidemiology and risk factors of this condition. This study
      describes the epidemiology of gingival recession in a representative, urban
      Brazilian population and assesses various risk indicators. METHODS: A
      representative sample of 1,460 subjects was selected using a multi-stage,
      probability, cluster sampling strategy. The subjects were interviewed using a
      structured questionnaire and had a full-mouth clinical examination in a mobile
      examination center. RESULTS: More than half (51.6%) and 22.0% of the individuals
      and 17.0% and 5.8% of teeth per individual showed gingival recession > or = 3 mm
      and > or = 5 mm, respectively. The prevalence, extent, and severity of recession
      correlated with age. Recession showed a nonlinear relationship with age, with 25
      to 50 year olds showing the highest level of recession. Males aged > or = 30
      years showed significantly higher prevalence and extent of gingival recession
      than females. The percentage of teeth with recession was significantly higher in
      the lower socioeconomic groups irrespective of age, and in subjects > or = 30
      years of age with irregular dental care than in subjects with regular care. Using
      a multivariable model, cigarette smoking and presence of supragingival calculus
      were the factors most significantly associated with localized and generalized
      recession, whereas gender, dental visits, and socioeconomic status were not
      significant risk indicators. CONCLUSIONS: The high level of gingival recession in
      this Brazilian population may be primarily related to destructive periodontal
      disease and is significantly associated with a high level of supragingival dental
      calculus and cigarette smoking. Population-based programs aimed at the prevention
      of periodontal diseases may reduce the prevalence of severe gingival recession in
      this and similar populations.

PMID- 15562917
TI  - Effectiveness of adjunctive low-dose doxycycline therapy on clinical parameters
      and gingival crevicular fluid laminin-5 gamma2 chain levels in chronic
      periodontitis.
AB  - BACKGROUND: Laminin-5 (Ln-5) is involved in the apical migration of epithelial
      cells during the development of periodontal pockets. Low-dose doxycycline (LDD)
      can therapeutically modulate the host response with its non-antimicrobial
      properties. In the present randomized, double-blind, placebo-controlled, parallel
      arm study, the effectiveness of LDD in combination with non-surgical periodontal
      therapy on gingival crevicular fluid (GCF) Ln-5 gamma2 chain fragment levels and
      clinical parameters in patients with chronic periodontitis was examined over a 12
      month period. METHODS: GCF samples were collected and clinical parameters
      including probing depth (PD), clinical attachment level, gingival index (GI), and
      plaque index were recorded. Thirty chronic periodontitis patients were randomized
      either to low-dose doxcycline or placebo groups. LDD group received doxycycline
      (20 mg, b.i.d.) for 3 months plus scaling and root planing (SRP), while placebo
      group was given placebo capsules b.i.d. for 3 months plus SRP. The patients were
      evaluated every 3 months during the 12-month study period. All clinical
      parameters and GCF sampling were repeated at each visit. GCF Ln-5 gamma2 chain
      fragment levels were determined by Western immunoblotting using specific antibody
      and quantitated by computerized image analysis. Friedman test was used for
      intragroup comparisons followed by Wilcoxon signed rank test to analyze
      significance of changes over time. The Mann-Whitney test was used to determine
      differences between both LDD and placebo groups. RESULTS: Both groups revealed
      significant improvements in all clinical parameters over the 12-month period (P <
      0.0125). LDD group showed a significantly greater reduction in the mean PD scores
      at 9 and 12 months and in the mean GI scores at all time points than the placebo
      group (P < 0.05). In the LDD group, GCF Ln-5 gamma2 chain fragment levels were
      significantly reduced at 3 months (P < 0.0125) and then slightly increased during
      the rest of the study period. In the placebo group, GCF 45 and 70 kDa Ln-5 gamma2
      chain fragments tended to decrease at 3 months compared to baseline, but did not
      reach significance; these levels continued to increase throughout the remainder
      of the study period. GCF Ln-5 gamma2 chain fragment levels in LDD group were
      significantly lower than those of the placebo group during the study period (P <
      0.05). CONCLUSIONS: The present data indicate that LDD therapy in combination
      with SRP therapy can reduce GCF Ln-5 gamma2 chain fragment levels and improve
      clinical periodontal parameters in patients with chronic periodontitis. Since
      matrix metalloproteinases (MMP)-mediated fragmentation of laminin-5 can
      contribute to pocket formation by stimulating epithelial cell migration, the
      reduction of Ln-5 gamma2 chain fragment levels could provide a new mechanism by
      which LDD, adjunctive to SRP, inhibits periodontal disease more effectively than
      SRP alone. Thus, these results provide extended and additional information about
      the effectiveness of the LDD therapy as an adjunct to non-surgical periodontal
      therapy in the long-term management of periodontal disease.

PMID- 15562918
TI  - Localized gingival recessions treated with the original envelope technique: a
      report of 50 consecutive patients.
AB  - BACKGROUND: The surgical techniques used to treat gingival recession have changed
      considerably in the last 50 years. The envelope technique described nearly 20
      years ago still offers an excellent alternative for the problem of recession. The
      purpose of this retrospective study is to show the results of 115 recession sites
      treated in 50 patients using the envelope technique. METHODS: One hundred-fifteen
      consecutive procedures were performed in 50 patients in a private practice in the
      last 5 years using the envelope technique. Briefly, the teeth are scaled, a split
      thickness flap is performed around the recession, a subepithelial connective
      tissue graft is harvested from the palate and placed over the recession, and
      sutured with 6-0 silk. Four cases representing different types of recession will
      be reviewed and all cases will be analyzed. RESULTS: In general, this surgical
      method provided excellent root coverage and an increased amount of keratinized
      gingiva. The complete root coverage mean was 85%, 65%, and 16% for recession
      Class I, II, and IV, respectively. CONCLUSION: The cases support the use of the
      envelope technique to treat different types of single and multiple recessions.

PMID- 15562919
TI  - Implant survival in periodontally compromised patients.
AB  - BACKGROUND: Relatively little is known on the long-term prognosis of implants
      inserted in partially edentulous, periodontally compromised patients. METHODS: A
      total of 258 conventional implants, 57 two-stage and 201 one-stage implants,
      which were inserted in 32 and 108 patients, respectively, between June 1988 and
      June 2002 were followed with respect to their survival, as well as the
      periodontal parameters bone loss, probing depth, and bleeding on probing. All
      patients were periodontally compromised who had undergone periodontal surgery and
      were considered able to maintain a high standard of oral hygiene. RESULTS: The 5
      year survival rates were 97% and 94%, respectively, for the two- and the one
      stage implants. The 10-year survival rate remained high at 97% for the two-stage
      implants, but had dropped to 78% for the one-stage implants. Smoking, short
      implant length, and insertion during the later period (1995-2002) were found to
      be associated with an increased failure rate. CONCLUSIONS: Implants placed in
      patients with a history of periodontitis have a 5-year survival similar to that
      observed for implants installed in non-diseased persons. Although the 10-year
      survival of the one-stage implants was somewhat lower than has been observed for
      non-diseased patients, implant placement remains a good treatment alternative
      also for periodontally compromised patients.

PMID- 15562920
TI  - Morbidity and economic complications following mucogingival surgery in a
      hemophiliac HIV-infected patient: a case report.
AB  - BACKGROUND: This report describes the surgical treatment of a gingival recession
      in a hemophiliac HIV-infected patient. To our knowledge, mucogingival surgery has
      not been described previously in these patients. METHODS: Under the supervision
      of the patient's hematologist, a subepithelial connective tissue graft procedure
      was carried out to treat the recession. The treatment was performed after
      substitution therapy with factor VIII concentrate, supported by local
      antifibrinolytic treatment with epsilonaminocaproic acid. RESULTS: One week after
      surgery, the grafted zone showed a normal healing, but an area of necrosis
      appeared at the donor palatal site with spontaneous bleeding. The administration
      of factor VIII concentrate had to be prolonged to arrest the hemorrhage. In
      total, 44,500 units of factor VIII concentrate were used, the cost of which
      reached around $20,000. After 1 month the donor site had re-epithelialized by
      secondary intention. The root coverage was around 85% successful. CONCLUSIONS:
      Because of the surgical risk and the high economic cost in the use of the factor
      VIII concentrate, we do not recommend performing mucogingival surgery in HIV
      infected hemophiliacs unless it is absolutely necessary. Prevention and early
      treatment must be the goal in the management of these patients.

PMID- 15562921
TI  - Submental cutaneous sinus tract as a result of progressive peri-implantitis: a
      case report.
AB  - BACKGROUND: The aim of the present case report was to define diagnosis and
      treatment options of a submental cutaneous sinus tract as a result of a
      progressive peri-implantitis around mandibular dental implants in a patient with
      a history of oral squamous cell carcinoma. METHODS: Before the removal of the
      submental fistula, a panoramic radiograph and a computed tomography of the head
      and neck were assessed to identify the implants responsible for the cutaneous
      sinus tract and to exclude the presence of a tumor recurrence and lymph node
      metastases. The involved implants were removed, as there was a communication
      along them between the oral cavity and the cutaneous sinus tract resulting from
      progressive peri-implantitis. A histological examination of the excised fistula
      was carried out. RESULTS: The histological examination excluded a recurrence of
      the oral squamous cell carcinoma. The fistula completely consisted of granulation
      tissue without epithelialization. After affected implants were removed, the wound
      healing was uneventful. CONCLUSIONS: A panoramic radiograph is mandatory to
      identify the involved implants. Computed tomography, and excision of the fistula
      and a histological examination should be performed only in patients with a
      history of oral squamous cell carcinoma. Since the cutaneous sinus tract showed
      no epithelialization, it healed spontaneously after the removal of the
      responsible implants. Because of the large bony defect caused by progressive peri
      implantitis leading to a communication of the oral cavity with the cutaneous
      sinus tract, more conservative treatment options with preservation of the
      implants could not be adopted in the present case.

PMID- 15562922
TI  - Drug-associated gingival enlargement.

PMID- 15562923
TI  - Does mild pulmonary stenosis progress during childhood: a study of its natural
      course.

PMID- 15562924
TI  - Reperfusion of myocardium does not necessarily equate with epicardial coronary
      artery blood flow.

PMID- 15562925
TI  - Anticoagulation for atrial fibrillation: underutilization in a Brazilian tertiary
      outpatient clinic.
AB  - Despite a clear benefit of anticoagulation in patients with atrial fibrillation
      for the prevention of stroke, treatment rates are disappointingly low in clinical
      practice in the industrialized countries. This survey demonstrates similar rates
      in a Brazilian tertiary outpatient clinic, with only 55% of patients at high risk
      receiving dose-adjusted warfarin. Poor patient education and health care system
      limitations are considered important barriers. Strategies to improve treatment
      rates should target specific problems at each location.

PMID- 15562926
TI  - Limiting brain and lung damage after coronary artery bypass grafting: an
      alternative to conventional coronary artery bypass graft.
AB  - The development of coronary artery bypass graft (CABG) for the treatment of
      coronary heart disease has resulted in reduced morbidity and mortality compared
      with medical therapy. Even with the rapid development of improved percutaneous
      interventions, CABG remains an important approach for treating patients with
      advanced coronary heart disease. However, recent studies and commentary reporting
      an alarmingly high incidence of subtle, cognitive decline following CABG have
      generated questions about whether these adverse outcomes could be lessened. Even
      after considerable study, there is no consensus as to the cause of brain and lung
      injury after CABG and cardiopulmonary bypass, nor an agreed upon, mechanistic
      approach to study its prevention. The potential causes of these adverse outcomes
      and a simple approach are described, involving the use of the cannulae,
      biventricular pulsatile flow pump, and a blood substitute to optimize the
      perfusion of brain and alveolar cells, minimize systemic microembolization, and
      limit post-CABG cognitive decline.

PMID- 15562927
TI  - Utilization of low-profile intra-aortic balloon catheters inserted by the
      sheathless technique in acute cardiac patients: clinical efficacy with a very low
      complication rate.
AB  - Initial intra-aortic balloon pump (IABP) catheters were of large caliber and
      their utilization resulted in a high incidence of complications, including limb
      ischemia, bleeding and thrombosis, peripheral neurologic sequelae, and infection.
      Despite eventual decrease in the size of IABP catheters, the complication rate
      has remained high. HYPOTHESIS: The study was undertaken to determine whether use
      of recently available low-profile IABP catheters would result in a lower
      incidence of vascular and bleeding complications. METHODS: We prospectively
      evaluated the incidence of complications when consecutively using the low-profile
      (8F) IABP catheter inserted mostly sheathlessly in 161 acute cardiac patients
      between January 1, 2000 and April, 2003. RESULTS: Complications encountered
      included mild transient limb ischemia in two patients (1.2%), minor bleeding
      episodes in four patients (2.4%), one major puncture site bleeding (0.6%), and a
      pseudoaneurysm treated percutaneously in two patients (1.2%). Two patients (1.2%)
      suffered limb ischemia due to embolization or local thrombosis requiring vascular
      intervention. These complications were milder and their incidence remarkably
      lower than those reported previously when IABP catheters larger than 8F were
      used. CONCLUSION: Utilization of low-profile IABP 8F catheters in a sheathless
      technique entails an exceedingly low complication rate despite an acute
      presentation, intense anticoagulant and antiaggregant therapy, frequent
      comorbidity, advanced age, severe coronary disease, and reduced cardiac function
      in a large proportion of treated patients.

PMID- 15562928
TI  - Protruding left atrial myxoma presented with congestive heart failure and
      transient ischemic attack.

PMID- 15562929
TI  - Role of N-acetylcysteine in prevention of contrast-induced nephropathy after
      cardiovascular procedures: a meta-analysis.
AB  - BACKGROUND: Contrast-induced nephropathy is one of the common causes of acute
      renal insufficiency after cardiovascular procedures. HYPOTHESIS: The objective of
      this paper was to analyze the published data on the usefulness of N
      acetylcysteine in the prevention of contrast-induced nephropathy after these
      procedures. METHODS: Trials were selected if they were prospective, randomized,
      controlled, had selected patients with impaired renal function, used low
      osmolality, nonionic contrast media intra-arterially, administered a total of
      four doses of N-acetylcysteine in addition to intravenous saline hydration, and
      had contrast-induced nephropathy as their primary outcome. Contrast-induced
      nephropathy was defined as an increase in serum creatinine concentration by >0.5
      mg/dl or a 25% increase above baseline at or within 48 h post procedure. Meta
      analysis was performed using the Fisher's Combined Test with a measure of effect
      size. The magnitude of the N-acetylcysteine effect was estimated using random
      effects models. Homogeneity was evaluated using the chi-square test of
      homogeneity and standard Q statistic. Reporting bias was explored by the
      Rosenthal method. RESULTS: The Fisher's Combined Test was significant at p <
      0.005 in favor of N-acetylcysteine. The size of the N-acetylcysteine effect was
      to reduce contrast-induced nephropathy by 20%. There was a 62% relative risk
      reduction in contrast-induced nephropathy with N-acetylcysteine using a fixed
      effects model, and a 70% relative risk reduction using the random-effects model.
      In addition, we found that 27 unpublished trials showing no effects of N
      acetylcysteine would exist to overturn the combined significance of p < 0.005 of
      the five trials in our meta-analysis. CONCLUSION: Oral administration of N
      acetylcysteine in addition to intravenous saline hydration has a beneficial
      effect in the prevention of contrast-induced nephropathy after cardiovascular
      procedures in patients with impaired renal function.

PMID- 15562930
TI  - Long-term outcome after senning operation for transposition of the great
      arteries.
AB  - BACKGROUND: The Senning operation for transposition of the great arteries (TGA)
      was first introduced by Senning in 1959 and was revived by Quaegebeur et al. in
      the late 1970s, thus becoming the intervention of choice for the correction of
      TGA in many centers. HYPOTHESIS: The purpose of this study was to evaluate the
      long-term follow-up of a group of patients undergoing surgery with the Senning
      procedure for TGA. METHODS: From November 1978 to November 1987, 73 consecutive
      patients underwent the Senning operation. The 70 survivors had an average follow
      up of 19 years (16-25 years). RESULTS: (1) Cardiac rhythm: with time there was a
      progressive decrease in stable sinus rhythm (60% after 20 years) and a
      progressive increase of supraventricular tachyarrhythmias requiring therapy (10%
      after 20 years). (2) Right ventricular function: 20% of the patients had reduced
      ejection fraction. (3) Late mortality: in the last 12 years of follow-up years
      there were two sudden deaths (2.8%). (4) Functional status: 80% of patients were
      in NYHA class I, 17% in class II, and 3% in class III. CONCLUSIONS: Our results
      confirm that the patients who undergo the Senning procedure have a progressive
      loss of sinus rhythm, an increase in active arrhythmias, and other important
      adverse outcomes such as late sudden death and a decrease in right ventricular
      function; however, most patients (93% in our series) are alive and in good
      functional status.

PMID- 15562931
TI  - Prospective validation of a quantitative method for differentiating ischemic
      versus nonischemic cardiomyopathy by technetium-99m sestamibi myocardial
      perfusion single-photon emission computed tomography.
AB  - BACKGROUND: Myocardial perfusion single-photon emission computed tomography
      (SPECT) permits assessment of stress perfusion and resting left ventricular (LV)
      function. Quantitative analysis of perfusion patterns among patients with LV
      dysfunction offers an opportunity for developing criteria to differentiate
      ischemic from nonischemic cardiomyopathy. HYPOTHESIS: Quantitative assessment of
      SPECT may allow differentiation between ischemic and nonischemic cardiomyopathy.
      METHODS: We evaluated 144 patients with LV ejection fraction < or =40%, divided
      into 63 patients with nonischemic and 81 with ischemic cardiomyopathy. Mean
      relative myocardial counts were obtained for regions drawn over defect and normal
      zones on rest and stress polar perfusion maps. RESULTS: Multivariate logistic
      regression analysis of significant univariate SPECT predictors of ischemic
      cardiomyopathy revealed that the stress defect severity ratio (SDSR) was the best
      predictor of ischemic cardiomyopathy (p < 0.0001). By receiver operator
      characteristic (ROC) curve analysis, an SDSR of < or =45% optimized prediction of
      ischemic cardiomyopathy (sensitivity 81%, specificity 96%). An SDSR of < or =45%
      occurred in 65 of 81 (80%) patients with ischemic cardiomyopathy, but in only 3
      of the 63 (4%) patients with nonischemic cardiomyopathy (p < 0.0001). Applying
      the < or =45% SDSR threshold to a prospective group of 89 patients yielded a
      somewhat lower sensitivity (60%), but retained high specificity (91%) for
      identifying ischemic cardiomyopathy (p = NS vs. retrospective group).
      CONCLUSIONS: Presence of a severe and extensive stress perfusion defect is a
      hallmark of ischemic cardiomyopathy. By contrast, a mild stress perfusion defect
      (SDSR of >45%) is commonly present among patients with ischemic and nonischemic
      cardiomyopathy. An SDSR of < or =45% is a reproducible specific marker for
      identifying the presence of ischemic cardiomyopathy.

PMID- 15562932
TI  - Impact of left ventricular diastolic function on exercise capacity in patients
      with chronic mitral regurgitation: an exercise echocardiography study.
AB  - BACKGROUND: Mitral regurgitation (MR) is known as one of the most frequent causes
      of heart failure and sudden death. In spite of increasing prevalence of MR, there
      have been no available data on cardiac determinants of exercise capacity in
      patients with chronic MR. HYPOTHESIS: This study aimed to investigate cardiac
      determinants of exercise capacity in patients with chronic MR. METHODS: We
      consecutively enrolled 32 patients (11 men, mean age: 44 +/- 14 years) who had
      greater than moderate MR with normal left ventricular (LV) systolic function (LV
      ejection fraction >50%). Conventional echocardiographic indices and parameters
      measured by Doppler tissue imaging at septal side of mitral annulus were obtained
      before exercise. Mitral regurgitation fraction, forward stroke volume, pulmonary
      venous flow velocities, and systolic pulmonary artery pressure (sPAP) were also
      obtained with standard methods. RESULTS: Left ventricular ejection fraction was
      61 +/- 6% and MR fraction was 48 +/- 13%. All patients finished a symptom-limited
      treadmill exercise test with a peak heart rate of >85% of predicted maximum heart
      rate. Mean exercise time was 9.95 +/- 2.17 min, corresponding to 11 +/- 2
      metabolic equivalents. Among pre-exercise echocardiographic variables, only early
      diastolic mitral annulus velocity (E') and pulmonary venous reversal flow
      velocity (PVa) showed a significant correlation with exercise time (r = 0.44, p =
      0.011, and r = -0.40, p = 0.040, respectively), which persisted after
      multivariate analysis (p = 0.011 and 0.038, respectively). Other parameters such
      as systolic mitral annulus velocity, resting and postexercise sPAP, forward
      stroke volume, LV size, LV ejection fraction, left atrial size, and regurgitant
      fraction showed no significant correlation. CONCLUSIONS: Left ventricular
      diastolic function is an important determinant of exercise capacity in patients
      with chronic MR. Both E' and PVa, accepted surrogate estimates for LV diastolic
      function, may be useful for identifying patients with chronic MR and with poor
      exercise capacity.

PMID- 15562933
TI  - Relationship of carotid intima-media thickness, pulse wave velocity, and ankle
      brachial index to the severity of coronary artery atherosclerosis.
AB  - BACKGROUND: Carotid intima-media thickness (IMT), pulse wave velocity (PWV), and
      the ankle brachial index (ABI) are widely used noninvasive modalities for
      evaluating atherosclerosis. HYPOTHESIS: The aim of this study was to determine
      the relationship of carotid IMT, PWV, and ABI with the severity of coronary
      artery disease (CAD), expressed as the Gensini score, and the presence of
      coronary risk factors. METHODS: We examined 205 consecutive patients (mean age 65
      +/- 12 years) who were clinically suspected of having CAD and were scheduled to
      undergo coronary angiography. Carotid intima-media thickness, brachial-ankle PWV
      (baPWV), and ABI were measured in all subjects before they underwent coronary
      angiography. RESULTS: Of the 205 patients, 124 patients were diagnosed as having
      CAD based on the presence of >50% stenosis in a major coronary artery; the
      remaining 81 patients did not have CAD. A relatively good correlation was
      obtained between carotid IMT and the Gensini score (R = 0.411, p < 0.0001),
      whereas baPWV correlated only weakly with the Gensini score (R = 0.203, p =
      0.0035), and ABI did not correlate with it. A multiple regression analysis
      revealed that the Gensini score correlated significantly and independently with
      age, male gender, and carotid IMT. CONCLUSIONS: Of the three noninvasive methods,
      carotid IMT may be more useful for determining coronary artery atherosclerosis
      than baPWV or ABI.

PMID- 15562934
TI  - Hemodynamic significance of heart rate in neurally mediated syncope.
AB  - BACKGROUND: Vasovagal and vasodepressor syncope are used interchangeably in the
      literature to describe the common faint syndrome, now collectively named neurally
      mediated syncope. The significance of heart rate (HR) in these reflex-induced
      reactions remains unclear. HYPOTHESIS: The study was undertaken to investigate
      the hemodynamic significance of HR in tilt-induced neurally mediated syncope.
      METHODS: In all, 113 patients with syncope of unknown etiology were studied by
      head-up tilt test with invasive hemodynamic monitoring. Thirty-five patients (15
      women, 20 men, age range 21 to 72 years) developed syncope and were enrolled for
      analysis. The hemodynamic data were compared between patients who developed
      bradycardia (vasovagal group, n = 15) and those without bradycardia
      (vasodepressor group, n = 20). RESULTS: The baseline hemodynamic data (mean +/-
      standard deviation) and the hemodynamic responses after 10-min headup tilt were
      similar between patients in the vasovagal and vasodepressor groups. During
      syncope, patients with vasovagal reaction developed hypotension and paradoxical
      bradycardia (HR = 52.4 +/- 5.9 beats/min), while patients with vasodepressor
      reaction developed a precipitous drop in arterial blood pressure with
      inappropriate HR (105 +/- 21 beats/min) compensation. Patients with vasovagal
      syncope manifested a significantly lower cardiac index and a significantly higher
      systemic vascular resistance index than patients with vasodepressor syncope (1.47
      +/- 0.29 vs. 1.97 +/- 0.41 1/min/m2, p < 0.001 and 2098 +/- 615 vs. 1573 +/- 353
      dynes x s x cm(-5) x m2, p < 0.003, respectively). A positive correlation existed
      between HR and cardiac index (r = 0.44, p = 0.008) during syncope in the patients
      studied. CONCLUSIONS: These findings suggest that the hemodynamic characteristics
      of vasovagal and vasodepressor reactions are different, and that HR plays a
      significant role in neurally mediated syncope.

PMID- 15562935
TI  - An oxidized low-density lipoprotein receptor gene variant is inversely associated
      with the severity of coronary artery disease.
AB  - BACKGROUND: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX
      1) is the major receptor of oxidized LDL in endothelial cells. The expression of
      LOX-1 was shown to be upregulated in atherosclerotic lesions. Recently, LOX-1
      gene polymorphism (G501C) was reported to be associated with myocardial
      infarction (MI). HYPOTHESIS: Our study was undertaken to elucidate the
      association between this polymorphism and coronary artery disease (CAD). METHODS:
      We evaluated LOX-1 gene polymorphism using Invader assay in 586 patients
      undergoing coronary angiography. RESULTS: Study patients were categorized into
      three groups: normal/minimal stenosis (< or =25%) (n = 128); mild stenosis (26
      50%) (n = 39); and significant stenosis (>50%) (n = 419). Of the 419 patients
      with significant stenosis, 163 had single-vessel, 165 had double-vessel, and 91
      had triple-vessel disease. Myocardial infarction was present in 171 patients. The
      frequency of LOX- 1 gene variants (C/C or C/G) was lower in patients with
      significant than in those with normal/minimal stenosis (36 vs. 49%, p < 0.01).
      The frequency of LOX-1 gene variants did not differ between patients with and
      without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such
      variants was found depending on the severity of CAD: 49% in normal/minimal
      stenosis, 41% in mild stenosis, 39% in single-vessel, 35% in double-vessel, and
      32% in triple-vessel disease. Multivariate analysis demonstrated LOX-1 gene
      variants to be inversely associated with the presence of significant stenosis
      (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). CONCLUSIONS: The LOX-1
      gene variants at 501 were found to be inversely associated with the severity of
      CAD. This polymorphism may be modifying the severity of CAD.

PMID- 15562936
TI  - The incremental value of troponin-I testing in patients with intermediate risk
      unstable angina.
AB  - BACKGROUND: Classification of patients with unstable angina (UA) by Agency for
      Health Care Policy and Research (AHCPR) guidelines in the emergency department
      reliably stratifies risk of death or myocardial infarction (MI) for triage to
      outpatient evaluation (low-risk), hospitalization (high-risk), or additional
      testing (intermediate-risk). Cardiac troponin-I elevation may identify patients
      at higher risk, but the incremental value may vary with AHCPR clinical risk.
      HYPOTHESIS: The objective of this study was to determine whether cardiac troponin
      I had any additional value beyond triage based upon history, physical
      examination, and electrocardiogram, in the evaluation of patients with UA.
      METHODS: In all, 212 consecutive patients with UA and normal serum creatine
      kinase (CK)-MB levels and elevated troponin-I were risk stratified by AHCPR
      guidelines to evaluate the incremental value of adding routine troponin-I
      measurements to our current model for risk stratification. RESULTS: Primary
      events (death/nonfatal MI) occurred in 35% of high-risk, 15% of intermediate
      risk, and 0% of low-risk patients (p < 0.001 by chi-square for trend). High
      troponin-I (> or =2.0 ng/dl) occurred in 48% of high-risk, 21% of intermediate
      risk, and 19% of low-risk patients. The remaining patients in each risk group had
      indeterminate troponin-I levels (> or =0.4 < 2 ng/dl). Of those with high
      troponin-I, a primary event occurred in 36, 42, and 0% in the respective high-,
      intermediate-, and low-risk groups (p < 0.001). High troponin-I levels
      corresponded with a statistically significant increased rate of primary events
      only in patients at AHCPR intermediate risk: 42.4 vs. 7.3%, p < 0.001.
      CONCLUSION: The AHCPR guidelines risk stratify patients with UA. High troponin-I
      adds significant (p < 0.001) prognostic value in the patients at AHCPR
      intermediate risk and should be evaluated further in larger trials of such
      patients.

PMID- 15562937
TI  - The "ribbon sign" of aortic coarctation.

PMID- 15562938
TI  - Prognostic value of heterogeneity of ventricular repolarization in survivors of
      acute myocardial infarction.
AB  - BACKGROUND: The expansion of indications for implantation of cardioverter
      defibrillators (ICD) has enhanced the need for risk stratification of patients
      post myocardial infarction (MI), while the improved treatment of acute MI has
      decreased mortality and diminished the prognostic power of traditional risk
      variables. HYPOTHESIS: Increased heterogeneity of ventricular repolarization
      quantified by TCRT (total cosine R-to-T, angular difference between spatial QRS
      and T loops, decreased with increase in repolarization heterogeneity) is an
      independent predictor of mortality in patients post MI. METHODS: Left ventricular
      ejection fraction (EF), QRS duration on signal-averaged ECG, number of
      ventricular ectopic beats (VE)/h, heart rate variability (HRV) triangular index,
      heart rate turbulence slope on 24-h Holter recording, and TCRT were analyzed in
      334 survivors of acute MI followed up for 41 +/- 20 months. RESULTS: In
      multivariate analysis, EF < 35% (relative risk [RR] 2.3, 95% confidence interval
      [CI] 1.1-4.7, p = 0.023), VE > 10/h (RR 2.2, CI 1.0-4.6, p = 0.044), HRV < 20 U
      (RR 2.2, CI 1.1-4.5, p = 0.032), and TCRT < -0.896 (RR 4.3, CI 2.2-8.5, p =
      0.00001) were independent predictors of cardiac mortality (11%). Independent
      predictors of arrhythmic mortality (5%) were VE, HRV, and TCRT (RR 5.8, CI 2.1
      15.6, p = 0.0004). Cardiac and arrhythmic mortality of patients with both EF <35%
      and TCRT < -0.896 were >60 and >30%, respectively, compared with 17 and 7% in
      those with only EF <35% or TCRT < -0.896. CONCLUSION: Decreased TCRT, which
      reflects increased repolarization heterogeneity, is a strong and independent
      predictor of cardiac and arrhythmic death in patients post MI.

PMID- 15562939
TI  - Otto Frank and the fascination of high-tech cardiac physiology.

PMID- 15562940
TI  - Twelve-month sealant retention in a school-based program using a self-etching
      primer/adhesive.
AB  - OBJECTIVES: Very little independent research has been done on the new self
      etching primer/adhesives in dentistry. A recent clinical study compared two
      sealant application techniques involving self-etching primer adhesives and the
      traditional phosphoric acid etch. The purpose of this study was to compare these
      two techniques in an Iowa school-based sealant program. METHODS: Twelve-month
      sealant retention data on 208 students from the Des Moines, Iowa, school-based
      sealant program were analyzed retrospectively. RESULTS: Sealant retention
      reported at the person level showed that 60 percent of the students who received
      sealants at the five schools had to be recalled at one year to have one or more
      surfaces resealed. A logistic regression model at the person level demonstrated
      that the phosphoric acid technique was six times as likely to have retention of
      all the sealed tooth surfaces as those sealed with Prompt-L-Pop. CONCLUSIONS: In
      this study, many students had to be recalled to the chair 12 months after sealant
      application due to incomplete retention. Though sealants were retained in larger
      numbers with phosphoric acid, overall sealant retention at the tooth level was
      lower than previously published for clinical studies and school-based programs.
      Examining retention data at the person level, however, allows program
      administrators to plan resources more effectively and reevaluate sealant protocol
      to ensure as few children return for sealant reapplication.

PMID- 15562941
TI  - Seasonal variation in fluoride intake: the Iowa fluoride study.
AB  - OBJECTIVES: Although patterns of fluid intake change seasonally, little is known
      about how fluoride intake varies by season. Since even short-term increases in
      fluoride intake could potentially lead to more dental fluorosis, it is valuable
      to assess the degree of seasonal variation to determine if it increases fluoride
      intake to levels that could be considered a concern in young children. METHODS:
      Questionnaires were mailed periodically to participants in the Iowa Fluoride
      Study beginning at 6 weeks of age and continuing for a number of years. Parents
      recorded the date; child's weight; estimates of the amounts of water and other
      beverages that their child consumed per week; the type and amount of any fluoride
      supplements used; and the type, amount, and frequency of dentifrice used, with an
      estimate of the proportion of dentifrice that was swallowed. Documented water
      fluoride levels from municipal sources and assay of individual sources were
      linked to water intake amounts. Total fluoride intake per kg body weight was
      estimated from water, other beverages, fluoride supplements, and ingested
      dentifrice. Generalized linear models compared temperature-related and seasonal
      effects after adjusting for the child's age. RESULTS: Separate analyses for ages
      0-12 months and 12-72 months showed different results. Children younger than 12
      months of age did not exhibit significant seasonal or temperature-related
      variation in any of the components of fluoride intake. Children aged 12-72 months
      had higher fluoride intake (mg F/kg bw) from beverages in summer (P<.05), and
      fluoride intake from beverages increased with monthly temperature (P<.001).
      CONCLUSIONS: Fluoride intake from beverages for children aged 12-72 months is
      slightly higher in the summer and increases with mean monthly temperature.
      Fluoride intake from supplements and dentifrice did not change significantly with
      either season or temperature.

PMID- 15562942
TI  - Enamel fluorosis prevalence after a 7-year interruption in water fluoridation in
      Jau, Sao Paulo, Brazil.
AB  - OBJECTIVES: This paper analyzes the impact of a 7-year interruption in water
      fluoridation on the prevalence of enamel fluorosis in Jau, state of Sao Paulo,
      Brazil. METHODS: Fluorosis prevalence (TF index) was evaluated in permanent
      maxillary central incisors of children (9-14 years old) that were 36 (n=81;
      cohort -36), 27 (n=81; cohort -27), and 18 months old (+/-1 month; n=89; cohort 
      18) in October 1991, when the breakstarted, and 18months old(+/-1 month;n=70;
      cohort 18) after that date. Children brushed their teeth prior to examination,
      which was conducted under natural light by three calibrated examiners (agreement
      87.8-93.8%, kappa 0.72-0.85). RESULTS: The fluorosis prevalence (TF> or =1) was
      7.41 percent, 3.70 percent, 7.87 percent, and 18.57 percent, respectively, for
      cohorts -36, -27, -18, and 18. The difference between cohort 18 and the other
      groups was statistically significant (Kruskall-Wallis test, P=.05). CONCLUSIONS:
      These results suggest that the fluoridated water is not an important risk factor
      for enamel fluorosis, since the prevalence of enamel fluorosis was low in the
      cohorts -36, -27, and -18 when fluoridated water was used.

PMID- 15562943
TI  - The association between tooth loss and coronary heart disease in men and women.
AB  - OBJECTIVES: This paper evaluates the relation of tooth loss to incidence of
      coronary heart disease in two large cohort studies. METHODS: Participants
      included 41,407 men and 58,974 women free of any cardiovascular diseases at
      baseline. We recorded 1,654 incident coronary heart disease events (562 fatal
      events) among men during 12 years of follow-up and 544 events (158 fatal events)
      among women during 6 years of follow-up. RESULTS: After controlling for important
      cardiovascular risk factors, compared to men with 25-32 teeth at baseline, men
      with 0-10 teeth had a significantly higher risk of coronary heart disease
      (relative risk [RR]= 1.36; 95 percent confidence interval [CI]=1.11, 1.67). The
      relative risk increased to 1.79 (95% CI=1.34, 2.40) when limited to fatal events.
      Women with 0-10 teeth were also at increased risk of coronary heart disease
      compared to women with 25-32 teeth (RR=1.64; 95% CI=1.31, 2.05). The association
      was similar for fatal events (RR= 1.65; 95% CI=1.11, 2.46). The association
      between number of teeth and incidence of coronary heart disease was similar
      between men with and without a history of periodontal disease, and there was no
      significant association between tooth loss during follow-up and coronary heart
      disease. CONCLUSIONS: This study showed a significant association between number
      of teeth at baseline and risk of coronary heart disease and the mechanisms to
      explain this association should be further clarified.

PMID- 15562944
TI  - Routine dental visits are associated with tooth retention in Brazilian adults:
      the Pro-Saude study.
AB  - OBJECTIVE: This study investigates the effect of routine visits for dental check
      up on tooth loss. METHODS: In a cross-sectional study of university employees,
      the Rio de Janeiro Pro-Saude Study, tooth loss was measured as the reported
      number of missing teeth and routine dental visit as the reported pattern and
      frequency of visits to the dentist. RESULTS: Data were obtained from 4,030
      individuals (91% of eligible subjects). Odds ratio of excessive tooth loss
      ("many" or "all" teeth lost) was 2.20 (95% confidence interval [CI]=1.79, 2.72)
      for subjects who reported visiting the dentist only when in trouble and 1.17 (95%
      CI=0.90, 1.51) for subjects who reported visiting for routine dental checks every
      two years or less frequently, compared with those who reported visiting for
      dental checks at least annually, after controlling for age, sex, education,
      income, race, smoking, and diet. CONCLUSIONS: There was a positive effect of
      routine visits for dental check-up on maintaining teeth. This effect was the same
      for one year and two years or longer intervals between check-ups.

PMID- 15562945
TI  - Use of preexisting radiographs for assessing periodontal disease in epidemiologic
      studies.
AB  - OBJECTIVES: This study evaluates the feasibility of obtaining preexisting dental
      radiographs by mail, the validity of assessing alveolar bone loss from posterior
      radiographs compared to full mouth, and the validity of alveolar bone loss
      assessed from radiographs taken at different times. METHODS: This investigation
      uses data obtained for a study evaluating associations between oral conditions,
      blood biomarkers, and coronary heart disease within two large cohorts: the
      Nurses' Health Study and the Health Professionals Follow-up Study. If consenting
      participants had dental radiographs, we requested these radiographs from their
      dentists. Some dentists returned multiple sets of radiographs, which enabled us
      to conduct this study. A calibrated periodontist read all radiographs with good
      intraexaminer reliability (r=0.91). We compared posterior radiographs to full
      mouth (n=121 sets), as well as radiographs taken at different times (mean
      difference of 5 years) (n=102 pairs). RESULTS: Of the 812 participants, 81
      percent consented and 66 percent provided radiographs. Posterior radiographs
      underestimated periodontitis (> or =1 site with > or =5 mm alveolar bone loss)
      prevalence by 6 percent (53.7% vs 57.0%) compared to full mouth, with sensitivity
      of 0.94 (95% confidence interval [CI]=0.86, 0.98) and specificity of 1. Spearman
      correlation coefficients comparing mean alveolar bone loss were 0.70 for anterior
      versus posterior teeth (mean difference=0.48), 0.92 for posterior teeth versus
      full mouth (mean difference=0.25), and 0.78 for pairs of radiographs taken at
      different times (mean difference=0.01). The kappa statistic was 0.70 comparing
      radiographs taken within 5 years and 0.29 when the period extended beyond 5
      years. CONCLUSION: Preexisting radiographs are feasible for use in epidemiologic
      studies and provide valid assessments of periodontal disease.

PMID- 15562946
TI  - Coverage and quality of oral cancer information in selected popular press: May
      1998 to July 2003.
AB  - OBJECTIVES: A 1998 study demonstrated a lack of coverage about oral cancer in the
      popular press between April 1987 and April 1997. Since that study, several oral
      cancer-related activities took place, many of which could have increased the
      media's attention to oral cancer. Therefore, this study analyzed coverage and
      quality of oral cancer information in selected popular press between May 1998 and
      July 2003. METHODS: Articles from magazines and newspapers were retrieved from
      three databases and were analyzed by specific topics and subtopics for adequacy
      of content and accuracy of information. Articles were categorized as either
      "primarily oral cancer-related" or "primarily tobacco-related." RESULTS: Sixty
      articles were identified, 39 of which were included in the analysis (14
      magazines; 25 newspapers). Seventeen articles were "primarily oral cancer
      related," and 22 were "primarily tobacco-related." Seventy-two percent of the
      articles mentioned at least one risk factor for oral cancer, the most common
      being tobacco use (69%). Far fewer articles noted alcohol (10%) or the combined
      use of tobacco and alcohol (5%) as risk factors. Only 8 percent of the articles
      recommended an oral cancer examination. CONCLUSION: Despite local and limited
      national efforts and activities aimed at increasing public awareness of oral
      cancer, the popular press coverage of those activities was minimal or
      nonexistent.

PMID- 15562947
TI  - Maintenance of optimal fluoride levels in public water systems.
AB  - OBJECTIVE: This study examines the quality of water fluoridation in public water
      supplies. METHODS: An assessment of daily fluoride levels among all communities
      that fluoridate their public water supplies in New Hampshire was conducted from
      January 1, 2000, through June 30, 2002. Results were compared against
      recommendations from the Centers for Disease Control and Prevention. RESULTS: The
      fluoride concentration was less than the recommended minimum value on 42.0
      percent of days, within the accepted control range on 49.8 percent of days, and
      above the recommended maximum value on 1.0 percent of days. On 7.1 percent of
      days, a fluoride concentration was not determined. Only 2 (18.2%) of 11 public
      water supplies maintained the fluoride concentration in the optimal range > or
      =80 percent of the days. CONCLUSIONS: For public water supplies in New Hampshire
      that fluoridate, suboptimal levels are the most common problem. Water systems
      need to better maintain recommended fluoride levels if communities are to realize
      the full benefits of fluoridation.

PMID- 15562948
TI  - Past and present geographic location as oral health markers among older adults.
AB  - OBJECTIVES: This study evaluated the association between oral health status of
      community-dwelling elderly adults visiting day health centers in Israel and
      geographic living location. METHODS: Oral status was assessed through clinical
      examination, with additional data obtained using a questionnaire addressing
      demographic characteristics, dental utilization, and perceived oral health needs.
      RESULTS: A representative sample of 338 subjects was examined. Fifty-four percent
      of the sample was edentulous. Higher rates of edentulism were found among
      subjects living in urban areas compared to subjects living in rural areas
      (P<.01). More edentate subjects were found among European immigrants than among
      immigrants from North Africa or subjects born in Israel (P<.01). Among dentate
      subjects, the mean number of remaining teeth was 10.4. The mean periodontal loss
      of attachment was 5.8 mm. Less than 10 percent had mean attachment loss <4 mm.
      Among subjects living in rural areas, mean attachment loss was higher than among
      those living in urban areas (P=.05). The mean DF score was 1.9. Forty-seven
      percent had at least one tooth with untreated caries. Subjects living in urban
      areas tended to utilize dental services more than subjects living in rural areas
      (P<.01). CONCLUSION: Results indicate that present (urban or rural) and past
      (country of origin) geographic location represented a significant oral health
      risk marker. The implementation of a comprehensive program for this target
      population was clearly indicated.

PMID- 15562949
TI  - Pediatricians' perception about the use of antibiotics and dental caries--a
      preliminary study.
AB  - OBJECTIVES: This study aimed to evaluate pediatricians' perception about the use
      of antibiotics and dental caries. METHODS: One hundred pretested questionnaires
      containing open and closed questions were distributed to pediatricians from
      public hospitals in Rio de Janeiro, Brazil. RESULTS: The response rate was 60
      percent. Considering the respondents, 73.3 percent frequently prescribed
      antibiotics, oral administration being the chosen mode (93.3%). Antibiotics were
      pointed out as being very sweet substances by 53.3 percent of the pediatricians.
      However, the same percentage did not know what sweetener was responsible for the
      sweet flavor, and just 40.6 percent recommended oral hygiene after the medicine's
      intake. Among the pediatricians, 56.7 percent related the use of antibiotics to
      the occurrence of dental effects, and 40 percent thought that antibiotics could
      cause a defect of tooth structure. Only one pediatrician (3.2%) associated the
      presence of fermentable carbohydrates in the composition of these medicines with
      dental caries. CONCLUSIONS: Pediatricians in this study did not perceive the
      correct relationship between the presence of fermentable carbohydrates in
      antibiotics and dental caries. Many of them believed these medicines promoted a
      defect of tooth structure favoring the development of dental caries. Further
      studies with a larger sample are necessary.

PMID- 15562950
TI  - Defective interleukin-2 production and interleukin-2 receptor expression in
      pulmonary tuberculosis.
AB  - The evolution of Mycobacterium tuberculosis as an intracellular pathogen has led
      to a complex relationship between it and its host, the human mononuclear
      phagocyte. The products of M. tuberculosis-specific T lymphocytes are essential
      for macrophage activation for intracellular mycobacterial killing. However,
      dysfunction cell-mediated immune response to infection with M. tuberculosis may
      contribute to progressive primary infection or reactivation of endogenous foci of
      mycobacteria. Th1 cells produce IL-2, which is essential for proper cellular
      immunity. The aim of this study was to identify the variation in IL-2 activity
      and soluble IL-2 receptor (IL-2 R) in peripheral blood lymphocyte in patients
      suffering with pulmonary tuberculosis. A significant decrease in IL-2 and IL-2
      receptor level was observed in patients with pulmonary tuberculosis when compared
      to normal controls. Our results suggested that patients with pulmonary
      tuberculosis had a defect in IL-2 production. Better understanding of these
      interactions will allow the development of increasingly specific immune-based
      interventions for prevention and treatment of tuberculosis.

PMID- 15562951
TI  - Evaluation of A newly developed DOT-ELISA kit for the diagnosis of human
      brucellosis.
AB  - A new dot-ELISA kit for detection of Brucella antibodies in human sera was
      developed and compared with that of serum agglutination test, Rose Bengal plate
      test, rapid slide agglutination and Coomb's antiglobulin test. Following testing
      of 120 human sera from suspected patients of occupational risk, 25 gave positive
      reaction in Rose Bengal plate test, 25 in rapid slide agglutination test, 26 in
      serum agglutination test, 27 in Coomb's antiglobulin test and 28 in dot-ELISA
      kit. Dot-ELISA kit picked up more positive than any other Serological test,
      indicating its superiority over the other laboratory tests for the diagnosis of
      brucellosis.

PMID- 15562952
TI  - Drug resistance in tuberculosis in Delhi: a 2 year profile (2001--2002).
AB  - 234 isolates of Mycobacterium tuberculosis obtained from 1000 suspected cases of
      tuberculosis reporting at National Institute of Communicable Disease, Delhi for
      laboratory investigation between Jan 2001 to August 2002 were subjected to
      invitro drug sensitivity test against the first line drugs (Isoniazid,
      Streptomycin, Rifampicin, Ethambutol and Thiacetazone) by proportion method using
      Lowenstein Jensen (LJ) media. Out of 234 isolates of Mycobacterium tuberculosis,
      142 were from cases of untreated tuberculosis, whereas only 92 isolates were from
      treated cases of tuberculosis. An initial drug resistance of 21.83% was seen
      against INH, 9.85% against Streptomycin, 15.49% against Rifampicin, 4.22% against
      ethambutol and 2.11% to thiacetazone. Multidrug resistance (MDR-i.e. Resistance
      to both INH and Rifampicin) was seen in 11.97% of isolates. 4(2.8%) isolates were
      found to be resistant to all drugs tested. A much higher level of acquired
      resistance was seen the figures being 61.95% for INH, 53.36% for rifampicin,
      35.86% for streptomycin, 20.65% for ethambutol and 10.86% for thiacetazone. Avery
      high acquired MDR to the tune of 42.39% was seen. 24(26%) isolates were found to
      be resistant to all drugs tested. No significant difference were observed in the
      drug resistance pattern between pulmonary and extrapulmonary cases of
      tuberculosis in both initial and acquired drug resistance category.

PMID- 15562953
TI  - Prevalence of initial drug resistance to M. tuberculosis in new sputum positive
      RNTCP patients.
AB  - There is an increased prevalence of drug resistant M. tuberculosis strains and of
      these, multi drug resistant organisms are of particular concern. With the
      implementation of Revised National Tuberculosis Control Programme (RNTCP) allover
      the state of Delhi, Initial drug resistance (IDR) to Isoniazid and Rifampicin
      assumes great importance and needs to be monitored on a regular basis. We
      undertook to study the IDR against the first line essential drugs i.e. Isoniazid
      (H), Rifampicin (R), Ethambutol (E) and Streptomycin (S) from April 1999 to March
      2000 in newly diagnosed sputum positive cases of pulmonary tuberculosis attending
      TB clinics under RNTCP in Delhi. A total of 157 consecutive new smear positive
      patients attending TB clinics under RNTCP were taken into the study. All sputum
      samples were subjected to culture and drug sensitivity tests on LJ medium after
      decontamination of samples by Petroff's method. Resistance was expressed as the
      percentage of colonies that grow on critical concentration of the drugs. To
      determine the proportion of resistance, the number of colonies on the control and
      the number of colonies on the drug medium were determined. A total of 94.77%
      samples were sensitive to the four first line essential drugs and IDR to any drug
      was 5.22%. The resistance to Rifampicin alone was nil but the resistance to
      Isoniazid alone was 2.24%. Combined resistance to both Rifampicin and Isoniazid
      was 2.98 %. The incidence of resistance to first line drugs in tuberculosis is
      not very high among new sputum positive patients attending TB clinics under
      RNTCP.

PMID- 15562954
TI  - A study of HIV/STD infections amongst commercial sex workers in Kolkata (India).
      Part-I: some socio-demographic features of commercial sex workers.
AB  - A community-based survey of Human Immunodeficiency Virus (HIV) and sexually
      transmitted diseases (STD) was carried out among commercial sex worker's (CSW) in
      different red light areas of Kolkata. By multistage random sampling technique 867
      female sex workers (FSW) studied who were belonging to Sonagachi 77.28%,
      Metiabruz 14.07%, Rampurgali and Khidderpore 8.65% red light areas. Among sex
      workers surveyed 58.94% were Hindu and 33.33% Muslims. There were 22.07% CSW of
      foreign origin, out of which 17.99% from Bangladesh and 4.04% from Nepal.
      Majority of CSW 74.28% were under thirty years of age. The lowest age was 13
      years and mean age was 26.55 years. There were 22.26% sex workers under twenty
      years and 6.92% above forty years of age. About 79.0% of sex workers were
      illiterate. The average number of clients visiting each sex workers was 2.67,
      with a range between 1 to 8 clients per day. The average duration for which sex
      workers remain in the trade was 6 to 7 years. Around 60.09% sex workers were in
      the trade for five years, while 2.64% were for more than twenty years. Average
      monthly income of sex workers was around Rs. 500-1000. History of pregnancy was
      present in 84.66% with one child in 24.91 % to maximum eight in 0.23% sex
      workers. The mean number of pregnancies was 1.9 per female sex workers. About
      36.2% had history of abortion and 65.51 % had living children.

PMID- 15562955
TI  - Laboratory studies on the predatory potential of dragon-fly nymphs on mosquito
      larvae.
AB  - Biocontrol potential of dragonfly nymph, Brachythemis contaminata Fabricius
      against the larvae of Anopheles stephensi, Culex. quinquefasciatus and Aedes
      aegypti was studied under laboratory conditions. It was found that dragonfly
      nymph had highest predation efficacy against An. stephensi followed by Cx.
      quinquefasciatus and Ae. aegypti. Feeding rate increased with decrease in prey
      size/stage. Analysis of data indicated that dragonfly nymphs have good predatory
      potential and can be used as a biological control agent for control of mosquito
      breeding.

PMID- 15562956
TI  - Increasing prevalence of antibiotic resistance and multi drug resistance among
      uropathogens.
AB  - A study was conducted to examine the prevalence of antibiotic resistance in the
      strains of bacteria isolated from patients with suspected urinary tract
      infection. A total of 348 bacterial isolates were grown from semi quantitative
      urine culture and were of significant bacteriuria. The antibiotic susceptibility
      testing was performed on Muller-Hinton agar by disc diffusion method according to
      the standard criteria of the National Committee for Clinical Laboratory
      Standards, Antibiotic susceptibility testing revealed a high prevalence of
      resistance to ampicillin (55.4%) followed by nitrofurantoin (45.4%), gentamicin
      (45.1%), amikacin (41.4%) and co-trimoxazole (30.5%). E. coli and Klebsiella
      pneumonia showed 78.8 % and 75.3 % resistance to three or more drugs
      respectively. Cefotaxime (87.1%) appeared to be the most active antibiotic
      against the majority of isolates, followed by Norfloxacin (83.3%).

PMID- 15562957
TI  - Is education a determinant of knowledge about malaria among Indian tribal
      population?
AB  - Malaria is a major public health problem in tribal villages of India, where 8% of
      the country's population lives. Literacy level among tribal population is very
      low. This study aims to examine the relation between education status and
      knowledge about malaria among Indian tribal communities. 125 randomly selected
      tribal respondents from one tribal village each of 17 states were administered a
      close ended questionnaire by trained interviewers to assess their knowledge about
      various aspects of malaria. Effect of educational status on the level of
      knowledge was analyzed using chi square test. Stratified analysis was performed
      using Mantel Haenszel chi square test to eliminate gender bias. 2125
      respondents', randomly selected from 17 tribal villages in as many states,
      findings were analyzed. Fifty seven percent male and 72% female respondents were
      illiterate. Only 2% respondents had college level education. Educated females
      were more knowledgeable than their male counterparts. Mantel Haenszel chi square
      analysis showed that educated respondents were more knowledgeable than the
      illiterates, after adjusting for sex of respondents. However, there was gross
      lack of knowledge regarding diagnosis and treatment of malaria and use of
      insecticides irrespective of gender and educational status. Improvement in
      literacy status of tribal population will help in increasing awareness about
      malaria. Opportunities for disseminating information about various aspects of
      malaria should be utilized during treatment of malaria cases by health workers.

PMID- 15562958
TI  - Susceptibility status of Japanese encephalitis vectors in Kurnool and
      Mehboobnagar districts of Andhra Pradesh, India.
AB  - An entomological survey in Kurnool and Mahboobnagar districts of Andhra Pradesh
      state, India was undertaken in January, 2002 to find out vector population of
      Japanese Encephalitis and their susceptibility status to different insecticides.
      Five Culicine species viz. of Cx. tritaeniorhynchus, Cx. vishnui, Cx.
      pseudovishnui, Cx. bitaeniorhynchus, Cx. gelidus were captured during the survey.
      Another suspected vectors Anopheles subpictus and An. hyrcanus were also
      prevalent in the study villages. The larval population showed a high degree of
      resistance to Fenthion and Temephos. The test mortality to DDT ranged between 75%
      and 90%. The mortality of Cx. tritaeniorhynchus, Cx vishnui and An. subpictus
      ranged from 85% to 95%. Cx. tritaeniorhynchus is susceptible to Deltamethrin and
      Cyfluthrin. Cx. vishnui showed 80 % and 85% mortality to DDT and Malathion
      respectively.

PMID- 15562959
TI  - Bacteriological study of bottled drinking water marketed in Mangalore.
AB  - Bottled water is generally accepted as safe for consumption. However, its
      potability is uncertain. Ninety samples of Six national and 3 local brands
      marketed in Mangalore City were studied. Seven of these were ISI certified.
      Bacteriological analysis of these samples were carried out for viable count,
      presumtive coliform count by multiple tube method, confirmed Esch. coli count by
      Eijkman test and specific intestinal pathogens, such as Salmonella, Shigella and
      Vibrios. Thirty out of 90 samples though free from coliforms, had viable count
      much higher than specified by Bureau of Indian Standard. Three samples of one of
      the brands which is ISI not certified had Esch. coli with most probable number
      18/100 ml and Salmonella typhimurium. It is concluded that bottled water can not
      be taken for granted to be safe.

PMID- 15562960
TI  - Effectiveness of training on the knowledge about HIV/AIDS amongst group "D"
      workers in Delhi.

PMID- 15562961
TI  - Resistant coagulase negative staphylococci from clinical specimen in and around
      Solapur (South Maharashtra).

PMID- 15562962
TI  - Potency evaluation of TOPV in West Bengal and three other states of eastern zone,
      during 1996--1998.

PMID- 15562963
TI  - Infestation of Enterobius vermicularis in the nasal mucosa of a 12 yr old boy--a
      case report.

PMID- 15562964
TI  - [A new N-acyl derivative of (S)-cysteine for quantitative determination of
      enantiomers of amino compounds by HPLC method with a precolumn modification with
      o-phthalaldehyde].
AB  - N-Phenylacetyl-(R)-phenylglycyl-(S)-cysteine (NPPC) was used for the
      determination of enantiomers of primary amines by rpHPLC with a precolumn
      modification with o-phthalaldehyde. NPPC was compared with the classic SH reagent
      N-acetyl-(S)-cysteine (NAC) in the analysis of stereomers of nonfunctionalized
      amines and amino alcohols. After the NAC modification, the resulting
      diastereomeric isoindoles were difficult to separate by HPLC, and satisfactory
      resolution was achieved only for some aliphatic amino alcohols. The use of NPPC
      improved the chromatographic analysis of stereomeric amino alcohols and, in
      addition, allowed the enantiomeric analysis of the nonfunctionalized amines.
      Similarity between the side radicals of the amino component and the thiol reagent
      favored the diastereomer separation. This method was used for determination of
      the absolute concentration of individual enantiomers of amines in the course of
      stereoselective enzymatic reactions. The optically active NPPC was prepared with
      a high yield by a chemoenzymatic synthesis based on a regioselective acylation of
      the (S)-cysteine amino group in aqueous medium by the action of penicillin
      acylase. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562965
TI  - [Structure-function relationship between analogues of the antibacterial peptide
      indolicidin. I. Synthesis and biological activity of analogues with increased
      amphipathicity and elevated net positive charge of the molecule].
AB  - The antibacterial peptide indolicidin and a number of its analogues were obtained
      by solid phase synthesis. An optimized method of the synthesis using the Boc
      strategy was suggested. It was shown that the therapeutic index of indolicidin
      analogues increased with a decrease in the total positive charge of the molecule
      and its amphipathicity; i.e., the hemolytic activity of analogues within the
      range of concentrations examined was practically absent, while the antibacterial
      activity was preserved. The English version of the paper: Russian Journal of
      Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562966
TI  - [A new crystal form of the Fab fragment of a monoclonal antibody to human
      interleukin-2: the three-dimensional structure at 2.7 A resolution].
AB  - The three-dimensional structure of the antigen-binding fragment of a monoclonal
      antibody to human interleukin-2 in a new crystal form (space group P2(1)2(1)2(1);
      unit cell parameters: a = 42.82, b = 90.68, and c = 139.82 A) was determined by
      the X-ray molecular replacement method at the resolution of 2.7 A. The protein
      folding and the stereochemistry of its antigen-binding site were comparatively
      analyzed. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562967
TI  - [The influence of local changes in the temperature-dependent conformational
      mobility of thioredoxins on their thermostability].
AB  - For the development of a method for the prediction of single point mutations
      substantially affecting protein thermostability, we studied the effect of the
      E85R and R82E mutations on the thermostability of thioredoxins from Escherichia
      coli (Trx) and Bacillus acidocaldarius (BacTrx), respectively. The basic method
      of investigation was the molecular dynamics simulation of 3D protein models in a
      particular solvent at different temperatures (300 and 373 K). Some thermolabile
      regions in Trx, BacTrx, and their mutants were revealed by analyzing the
      temperature effect on the molecular dynamics of the protein molecule. The effect
      of single point mutations on the temperature changes of the protein conformation
      mobility in several thermolabile regions was found. The results of the
      calculations are in accord with the experimental data indicating that the
      mutation E85R increases Trx thermostability, whereas the mutation R82E decreases
      BacTrx thermostability. The thermostability of these proteins was revealed to
      depend on ionic interactions between the thermolabile regions. The single point
      mutations change the parameters of these interactions and make them more
      favorable in the E85R-Trx mutant and less favorable in the R82E-BacTrx mutant.
      The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004,
      vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562968
TI  - [Recombinant thymosin alpha1].
AB  - An artificial gene encoding thymosin alpha1 was obtained by the chemoenzymatic
      synthesis and cloned into Escherichia coli. An expressing recombinant plasmid
      containing the hybrid protein gene, which encodes amino acid sequences of
      thymosin alpha1 and the Saccharomyces cerevisiae intein Sce VMA, was constructed.
      The expression of the hybrid protein from the resulting hybrid gene in E. coli,
      the properties of the resulting hybrid protein, and the conditions for its
      nonenzymatic cleavage to thymosin alpha1 were studied. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also
      http: // www.maik.ru.

PMID- 15562969
TI  - [Polymethylene derivatives of nucleic bases with omega-functional groups. III. N
      [7-(2-oxocyclohexyl)-7-oxoheptyl]-substituted pyrimidines].
AB  - New polymethylene derivatives of nucleic bases containing a beta-dioxo function
      at the omega-position were synthesized by alkylation of uracil, thymine, and
      cytosine with 1-(7-chloroheptanoyl)cyclohexan-2-one, and their physicochemical
      properties were studied. The English version of the paper: Russian Journal of
      Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562970
TI  - [The tissue-specific methylation of human-specific endogenous retroviral long
      terminal repeats].
AB  - A possible involvement of retroelements in the epigenetic regulation of human
      gene expression was considered by the example of methylation of long terminal
      repeats (LTRs) of the human endogenous retrovirus family K (HERV-K). The
      methylation status of six HERV-K LTRs was determined in various gene-enriched
      regions of the human genome. The methylation of four LTRs was shown to be tissue
      specific. Our results correlated with published data on the tissue-specific
      changes in the expression level of human genes adjacent to the LTRs under study.
      The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004,
      vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562971
TI  - [The structure and specific features of the cDNA expression of the human gene
      MRPL37].
AB  - A 147-bp cDNA fragment was isolated from human lymphocytes activated with
      concanavalin A using the method of direct selection. A complete copy of the
      selected gene having total homology with the mitochondrial ribosomal gene MRPL37
      was obtained by the RACE (rapid amplification of cDNA ends) technique. The MRPL37
      gene was localized on human chromosome 1 using a DNA panel composed of somatic
      cellular human-hamster hybrids. The Northern blotting and RT-PCR (reverse
      transcription-polymerase chain reaction) demonstrated that the RNA of the human
      MRPL37 gene is widely represented in the lymphoma populations of Raji B cells and
      MT4 T cells, as well as in pancreas, liver, and lung embryonic fibroblasts WI-38
      and LEH. The highest expression level of the MRPL37 mouse homologue was found in
      the cells of skeletal muscles, the heart, and organs of reproductive system: the
      uterus, ovaries, and testicles. A comparative analysis of the MRPL37 amino acid
      sequence with those of proteins represented in the Fasta33 and GenBank databases
      showed a homologous region in MRPL37 and PDCD9 (programmed cell death 9, MPRS30)
      proteins. The chicken homologue of PDCD9 is interesting because its
      overexpression causes apoptosis of the mouse fibroblasts C3H10T1/2. The existence
      of a common domain indicates possible similar functional peculiarities of the
      PDCD9 and MRPL37 genes and may imply the MRPL37 involvement in the process of
      apoptosis. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562972
TI  - [Synthesis of the alkyl-type glycerolipids with functional groups in their polar
      domain].
AB  - A number of alkyl glycerolipids with short-chain substituents at the C2 atom of
      glycerol and functional groups (carboxy and amino) in the polar head were
      synthesized. Cationic alkyl glycerolipids with a hydroxyl function in the
      hydrophilic moiety were also obtained. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: //
      www.maik.ru.

PMID- 15562973
TI  - [Fluorescent-labeled lipophilic analogues of serotonin, dopamine, and
      acetylcholine: synthesis, mass spectrometry, and biological activity].
AB  - 4,4-Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl derivatives
      of serotonin, dopamine, choline, and N,N-dimethylaminoethanol, with the
      fluorescence maximum at 512 nm (lambda(exc) 470 nm), and 4,4-difluoro-5,7
      diphenyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl derivatives of choline and
      N,N-dimethylaminoethanol, with the fluorescence maximum at 554 nm (lambda(exc)
      470 nm), were synthesized. These compounds yield protonated molecular ions of
      100% intensity upon mass spectrometry with electrospray ionization at atmospheric
      pressure. The fragmentation of molecular ions under the conditions of secondary
      mass spectrometry mainly proceeds through the elimination of hydrogen fluoride
      from the fluorescent core of the molecules. Experiments on sea urchin Lytechinus
      variegatus embryos and larvae showed that these compounds easily penetrate into
      the cells and are accumulated in the cytoplasm. They do not differ in their
      biological activity from similar derivatives of arachidonic acid described
      previously and are agonists of serotonin or acetylcholine or antagonists of
      nicotinic acetylcholine receptors. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: //
      www.maik.ru.

PMID- 15562974
TI  - [Synthesis and chemical transformations of N-hydroxy- and N
      hydroxyalkylcycloimides of chlorin p6].
AB  - Two series of chlorin p6 13,15-cycloimides that differ in their substituents at
      the nitrogen atom of the additional six-membered ring were synthesized. The
      compounds of the first series have a hydroxyl, alkoxyl, or acyloxy group at the
      13,15-cycloimide nitrogen and those of the second series, residues of aliphatic
      alcohols. The cycloimides synthesized are satisfactorily stable and display an
      intensive light absorption maximum at 710-718 nm. Treatment of the cycloimides
      with sodium periodate in the presence of osmium tetroxide and with the Vilsmeier
      reagent resulted in the formation of 3-formyl- and 3-(2-formylvinyl)derivatives,
      respectively. The conversion of vinyl into formyl group or 2-formylvinyl group
      leads to an additional bathochromic shift of the long-wave maximum by 30 nm on an
      average. An extra hydroxy group was introduced at position 18 of the macrocycle
      to increase the cycloimide hydrophilicity. The English version of the paper:
      Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: //
      www.maik.ru.

PMID- 15562975
TI  - [Synthesis of cationic amphiphiles on the basis of deoxycholic acid].
AB  - Cationic derivatives of deoxycholic acid with N,N-dimethylenediamine, epsilon
      aminocaproic acid, and pyridine as polar heads were synthesized. The cationic
      groups were linked to 3alpha- and 12alpha-hydroxy groups of the steroid moiety
      through ester or urethane bonds. Liposomal formulations of the compounds
      synthesized may be used for gene delivery in cells. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also
      http: //www.maik.ru.

PMID- 15562976
TI  - [Inhibition of the peroxidase-catalyzed oxidation of chromogenic substrates by
      alkyl-substituted diphenols].
AB  - A comparative kinetic study of the peroxidase oxidation of three chromogenic
      substrates--2,2'-azino-bis(3-ethyl-2,3-dihydrobenzothiazoline-6-sulfonic acid), o
      phenylenediamine (PDA), and 3,3',5,5'-tetramethylbenzidine--inhibited by
      trimethylhydroquinone and six tert-butylated pyrocatechols (InH) was carried out
      at 20 degrees C in 0.015 M phosphate-citrate buffer (pH 6.0) containing organic
      cosolvents (0-10% ethanol or DMF). The inhibitors were quantitatively
      characterized by the inhibition constants (Ki), the duration of the lag period in
      the oxidation product formation (delta tau), and the stoichiometric coefficient
      of inhibition that specifies the number of radicals terminated by one InH
      molecule (f). The inhibition could be competitive, noncompetitive, mixed, or
      uncompetitive, which depended on the nature and structure of the chromogenic
      substrate-diatomic phenol pair. Various substrate-diatomic phenol pairs exhibited
      Ki values within the range of 11-240 microM and f values from 0.7 to 2.6. The
      absence of a lag period was characteristic of oxidation of the substituted o
      phenylenediamine-substituted pyrocatechol. The total kinetic parameters and
      properties of the components allowed us to suggest six chromogenic substrate
      substituted diatomic phenol pairs for use in test systems for the determination
      of antioxidant activity in human body fluids, natural biological preparations,
      and food. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

PMID- 15562977
TI  - [The effect of 15-ketosterol analogues with a 5,6-dimethylhept-3-en-2-yl chain at
      C17 on cholesterol metabolism in Hep G2 hepatoma cells].
AB  - The effect on cholesterol metabolism in Hep G2 hepatoma cells was studied for new
      analogues of 15-ketosterol [3beta-hydroxy-5alpha-cholest-8(14)-en-15-one] (I):
      (24S)-3beta-hydroxy-24-methyl-5alpha-cholesta-8(14),22-diene-15-one (II), (24S)
      3alpha-hydroxy-24-methyl-5-alpha-cholesta-8(14),22-diene-15-one (III), and (24S)
      24-methyl-5alpha-cholesta-8(14),22-diene-3,15-dione (IV). Analogues (I) and (II)
      were found to be equally effective inhibitors of cholesterol biosynthesis after a
      3-h incubation with Hep G2 cells; however, (II) produced a stronger inhibitory
      effect after a 24-h incubation or after an incubation of cells preliminarily
      treated with the inhibitor in a medium containing no ketosterol. The ability of
      ketosterols to inhibit cholesterol biosynthesis decreased in the order (II) >
      (IV) > (III). Ketosterol (II) inhibited, whereas ketosterol (III) stimulated the
      biosynthesis of cholesteryl esters. (IV) stimulated the biosynthesis of
      cholesteryl esters at a concentration of 1-10 microM and exerted no marked effect
      at a concentration of 30 microM. These results indicate that delta8(14)-15
      ketosterols containing a modified side chain are of interest as regulators of
      cholesterol metabolism in liver cells. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: //
      www.maik.ru.

PMID- 15562978
TI  - [Synthesis from tigogenin and antituberculosis activity of some of the
      derivatives of 5alpha-ketosteroid hydrazones].
AB  - Isonicotinoylhydrazones and thiosemicarbazones of some 5alpha-ketosteroids were
      synthesized from tigogenin, and their structures were confirmed by NMR and IR
      spectroscopy and mass spectrometry. Their antimycobacterial activities were
      studied, and it was shown that some of the synthesized isonicotinoylhydrazones
      exhibit a high antituberculosis activity. The English version of the paper:
      Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: //
      www.maik.ru.

PMID- 15562979
TI  - [Stabilization of G x C-containing DNA duplexes by polyamides with parallel
      orientation in the minor groove].
AB  - The polyamides based on 4-amino-1-methylpyrrol-2-carboxylic acid, 4-amino-1
      methylimidazole-2-carboxylic acid, and beta-alanine that stabilize
      oligonucleotide duplexes consisting of G x C pairs through parallel packing in
      the minor groove were studied. The initial duplex TTGCGCp x GCGCAA melts at 28
      degrees C; the TTGCGCp[NH(CH2)3COPyIm betaImNH(CH2)3NH(CH3)2][NH(CH2)3COIm
      betaImPyNH(CH2)3N(CH3)2] x GCGCAA duplex (bisphosphoramidate with parallel
      orientation of ligands, where Py, Im, and beta are the residues of 1-methyl-4
      aminopyrrol-2-carboxylic and 1-methyl-4-aminoimidazole-2-carboxylic acids and
      beta-alanine, respectively), at 48 degrees C; and the TTGCGCp[NH(CH2)3COIm
      betaImPyNH(CH2)3COIm betaImPyNH(CH2)3N(CH3)2] x GCGCAA duplex (a hairpin
      structure with antiparallel orientation), at 56 degrees C. The English version of
      the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see
      also http: // www.maik.ru.

PMID- 15562980
TI  - BAEPs averaging analysis using autoregressive modelling.
AB  - OBJECTIVE: The present paper introduces a new perspective on the classical
      ensemble averaging which can be useful to analyse the Brainstem Auditory Evoked
      Potentials (BAEPs). The analysis of the dynamics, related to the BAEP, is
      performed directly after its acquisition from the electroencephalogram (EEG).
      METHODS: The method primarily consists of dynamically modelling the averaged
      potential, obtained during the acquisition mode. Each averaging of signal at a
      given instant is considered as an autoregressive (AR) process. RESULTS: It has
      been shown that the predicting error power of AR modelling can be useful to
      provide an efficient tool to analyse the BAEPs. It has also been shown that the
      method is capable of taking the non-stationarities of both the BAEP and the EEG
      into account. CONCLUSION: In order to validate our approach, the proposed
      technique has been implemented for both simulated and real signals. This approach
      can also be employed in the context of estimating other evoked potentials and
      shows rich promise for potential clinical applications in future.

PMID- 15562981
TI  - Direct-current injury: electrochemical aspects.
AB  - Direct-current injuries have occurred to anesthetized patients connected to
      battery-operated medical devices. This study was designed to document the effects
      of direct current applied to two electrodes on a tissue surrogate (round steak)
      at room temperature. Direct current from a 9 V source was applied to a pair of
      stainless steel electrodes (1.6 cm diameter) spaced 4.3 cm center-to-center.
      Current flowed for 5 min increments at the first electrode site, 10 min at the
      second, 15 min at the third, etc. until at the last site, the current flowed for
      30 min. In all, 63 measurements were made with the pair of electrodes, which were
      changed if they became corroded. Lesion appearance, lesion size, pH and
      resistance were measured. It was found that the pH under the negative electrode
      became strongly alkaline (pH > 12) and acidic (pH < 5.0) under the positive
      electrode. The lesion under the negative electrode was red with a dark purplish
      ring that identified the electrode perimeter. The lesion under the positive
      electrode was more uniform and gray in appearance. The largest increase in lesion
      diameter occurred in the first 5 min. In all cases the resistance decreased with
      the passage of time. At the start of each experiment, both electrodes were shiny.
      At the end of each experiment the electrodes were different in appearance. The
      negative electrode retained its original shiny appearance but the positive
      electrode was pitted and dull in appearance, reflecting the different chemical
      reactions at each site. The lesions under the negative electrodes were more
      severe, indicating that alkali is more damaging than the acid environment that
      was produced electrolytically.

PMID- 15562982
TI  - N100 auditory potential and electroencephalogram discriminate propofol-induced
      sedation levels.
AB  - OBJECTIVE: In the present study, we evaluated the electroencephalogram (EEG) and
      auditory N100 potential (N100) before and during propofol-induced sedation. The
      aim was to test whether using EEG and N100 the level of sedation may be
      evaluated. METHODS: Twenty-nine cardiac surgery patients were studied. The EEG
      signal and the N100 potential were recorded at awake one day before the cardiac
      operation and two times after the operation, when the clinical level of
      postoperative propofol sedation was considered deep (Ramsay Score 6) and moderate
      (Ramsay Score 4). Discriminant analysis was used to select those spectral EEG
      and/or N100 variables which would predict the correct level of sedation best. The
      final classification was based on canonical discriminant functions and
      Mahalanobis' distance. RESULTS: The spectral EEG variables (slow/fast-ratio,
      delta, and beta2 powers) predicted the correct level of sedation with 81%
      (canonical discriminant functions) and 80% (Mahalanobis' distance) accuracy.
      Similarly, the N100 (amplitude, latency, and the first principal component)
      predicted the correct level of sedation with 91% and 92% accuracy, and the
      combination of the EEG and N100 with 96% and 93% accuracy. CONCLUSIONS: Our
      findings suggest that the combined use of EEG and N100 may help to differentiate
      the propofol-induced sedation levels, and thus be a useful compliment to clinical
      sedation scales.

PMID- 15562983
TI  - Increased tidal volume variability in children is a better marker of opioid
      induced respiratory depression than decreased respiratory rate.
AB  - OBJECTIVE: During opioid administration, decreasing respiratory rate is typically
      used as a predictor of respiratory depression. Prior to opioid-induced apnea,
      progressively irregular breathing patterns have been noticed. We hypothesize that
      opioid administration to children will increase tidal volume variability
      (TV(var)) and that this will be a better predictor of respiratory depression than
      a decrease in respiratory rate. METHODS: We recruited 32 children aged 2-8 years
      scheduled to undergo surgery. During spontaneous ventilation, flow rates and
      respiratory rates were continuously recorded, while remifentanil was infused at
      stepwise increasing doses each lasting 10 min. The infusion was continued until
      the patient showed signs of respiratory depression. Flow data from each dose was
      used to calculate tidal volumes, from which TV(var) was calculated. The
      respiratory rate and TV(var) during the last (D(last)), second to last (D-2), and
      third to last (D-3), administered doses were compared to those during baseline
      (fourth to last dose). We chose a threshold of TV(var) increase and compared it
      to a decrease in respiratory rate below 10 breaths per min as predictors of
      respiratory depression. RESULTS: Compared to baseline, the TV(var) increased by
      336% and 668% during D(-2) and D(last), respectively, whereas respiratory rate
      decreased by 14.3%, 31.7%, and 55.5% during D(-3), D(-2), and D(last),
      respectively. A threshold increase in TV(var) of 150% over baseline correctly
      predicted respiratory depression in 41% of patients, compared to a drop in
      respiratory rate correctly predicting 22% of patients. CONCLUSIONS: TV(var)
      increases as children approach opioid-induced respiratory depression. This is a
      more useful predictor of respiratory depression than a fall in respiratory rate
      because the TV(var) increase is 10 times the drop in respiratory rate. A TV(var)
      increase also correctly predicts respiratory depression twice as often as
      decreased respiratory rate and is independent of age-related alterations in
      physiologic respiratory rates.

PMID- 15562984
TI  - The influence of larger subcutaneous blood vessels on pulse oximetry.
AB  - OBJECTIVE: Recent studies have renewed interest in reflectance pulse oximetry,
      specifically for monitoring the patient's forehead. Blood circulation on the
      forehead immediately above the eyebrow is fed by arteries that branch from the
      internal carotid artery and lack the vasoconstrictor response present in more
      peripheral regions. Some investigators question, however, the reliability of
      monitoring SpO2 on the forehead due to prior reported inaccurate readings with
      reflectance sensors. The present study evaluates pulse oximetry accuracy when
      reflectance sensors are placed over potentially pulsing or moving larger arterial
      vessels, or over more homogeneous microvasculature devoid of larger subcutaneous
      vessels. METHODS. Ten healthy adult volunteers were fitted with reflectance pulse
      oximetry sensors and exposed to a controlled desaturation to 70%. Sensors were
      placed immediately above the left and right eyebrows as well as over the temple.
      Additionally, numerical modeling was used to simulate light signals and photon
      migration through a homogeneous tissue bed with an added static or dynamic
      artery. RESULTS: Sensors placed above the eyebrows tracked one another with
      significantly better accuracy than when comparing temple with the brow placement
      (RMS of the Differences = 1.12% vs. 4.24%, respectively). Photon migration
      simulations indicate that the detected light bypasses the interior of larger
      vessels, while vessel presence affects the red and IR light pulse amplitudes
      independent of SaO2. CONCLUSIONS: Placement of reflectance pulse oximetry sensors
      directly over larger cardio-synchronously pulsing or moving vasculature can
      significantly degrade SpO2 reading accuracy. Reflectance sensors placed low on
      the forehead directly over the eyebrow and slightly lateral to the iris appear to
      avoid such vasculature and provide consistent and accurate estimates of SaO2.

PMID- 15562985
TI  - A novel approach to measure cardiac output noninvasively: a comparison with the
      thermodilution method on critical care patients.
AB  - OBJECTIVE: To compare the accuracy and reliability of cardiac output (CO)
      measurement by a Noninvasive Hemodynamic Analyzer (NHA) to the thermodilution
      cardiac output (COTD) technique in ICU patients of cardiac condition. METHOD: ICU
      retrospective data collected in a 700-bed university-affiliated regional medical
      center. The data results from 203 patients who required invasive hemodynamic
      monitoring for clinical and/or surgical management. RESULTS: The ranges of the
      two CO measurements were: CO(TD) = 2.06 to 8.8 l/min and CO(NHA) = 2.06 to 8.46
      l/min, respectively. The Mean and SD of CO(NHA) = 4.819 l/min +/- 1.053 was near
      to CO(TD) = 4.902 l/min +/- 1.421. Variance was better for CO(NHA) = 1.110 l/min
      compared to CO(TD) = 1.421 l/min. Median of CO(NHA) showed 4.813 l/min and CO(TD)
      = 4.660 l/min. Bias was 0.083 l/min with 95% Confidence Interval (Precision): 
      0.26 to 0.040, and 95% Limits of Agreement was between -1.661 to 1.827 l/min.
      CONCLUSIONS: The results of this retrospective study indicate that the CO(NHA)
      technique may be a promising screening method. Additional studies are needed to
      explore its diagnostic trending capability. This noninvasive CO technique has
      been proven to be clinically accurate and may be applicable for telemedicine
      applications.

PMID- 15562986
TI  - Facilitated assessment of unconsciousness from morphologic changes in the
      bilateral posterior tibial nerve cortical somatosensory evoked potential under
      total intravenous propofol anesthesia during spine surgery.
AB  - OBJECTIVE: To describe a unique morphologic feature of the bilateral posterior
      tibial nerve cortical somatosensory evoked potential, the S-wave, which varies
      systematically with propofol infusion rate and which appears to be useful in
      guiding adequate propofol concentration levels during spine surgery. METHODS: Two
      illustrative cases were selected from a pool of 15,000 pediatric and adult
      patients (ages 8-85 years) who were undergoing corrective spine surgery in
      operating rooms of university and community hospitals. Anesthesia was maintained
      with a continuous intravenous infusion of propofol (125-225 microg/kg/min) along
      with intermittent boluses of narcotic and midazolam (1.0-2.0 mg) as needed.
      Characteristic metamorphosis of the bilateral posterior tibial nerve cortical
      somatosensory evoked potential, highlighted by the emergence of an additional
      middle-latency component labeled the S-wave, served as a neurophysiological
      marker of "light" propofol anesthesia prompting elevation of propofol infusion
      rate or bolus injection. RESULTS: The S-wave was routinely abolished with
      increased propofol infusion rate or bolus injection. In all instances increased
      propofol concentration levels produced a characteristic morphologic change in the
      posterior tibial nerve cortical somatosensory evoked potential consistent with a
      return to adequate anesthetic depth. Selected cases presented herein compare the
      S-wave technique to BIS and illustrate the usefulness of the S-wave in
      identifying inadequate depth of propofol anesthesia. CONCLUSIONS: The bilateral
      posterior tibial nerve cortical somatosensory evoked potential changes its
      morphology in predictable fashion with decreased depth of propofol anesthesia,
      allowing for anticipation of imminent anesthetic "lightening." It serves as a
      useful cross-check to Bispectral Index (BIS) or other "level of consciousness"
      EEG-based algorithms for monitoring depth of propofol anesthesia during prolonged
      corrective spine surgery.

PMID- 15562987
TI  - A Java applet for multiple linked visualization of protein structure and
      sequence.
AB  - The amount of biological data available from experimental techniques is huge, and
      rapidly expanding. The ability to make sense of this vast amount of data requires
      that we make correlations between distinct biological disciplines using
      visualization techniques to highlight the critical information. This article
      describes the visualization techniques of dynamic data brushing, view context
      maintenance, fisheye sequence view, and a magic lens that have been developed to
      display protein structure and sequence information.

PMID- 15562988
TI  - Molecular modelling prediction of ligand binding site flexibility.
AB  - We have investigated the efficacy of generating multiple sidechain conformations
      using a rotamer library in order to find the experimentally observed ligand
      binding site conformation of a protein in the presence of a bound ligand. We made
      use of a recently published algorithm that performs an exhaustive conformational
      search using a rotamer library to enumerate all possible sidechain conformations
      in a binding site. This approach was applied to a dataset of proteins whose
      structures were determined by X-ray and NMR methods. All chosen proteins had two
      or more structures, generally involving different bound ligands. By taking one of
      these structures as a reference, we were able in most cases to successfully
      reproduce the experimentally determined conformations of the other structures, as
      well as to suggest alternative low-energy conformations of the binding site. In
      those few cases where this procedure failed, we observed that the bound ligand
      had induced a high-energy conformation of the binding site. These results suggest
      that for most proteins that exhibit limited backbone motion, ligands tend to bind
      to low energy conformations of their binding sites. Our results also reveal that
      it is possible in most cases to use a rotamer search-based approach to predict
      alternative low-energy protein binding site conformations that can be used by
      different ligands. This opens the possibility of incorporating alternative
      binding site conformations to improve the efficacy of docking and structure-based
      drug design algorithms.

PMID- 15562989
TI  - Scoring protein-protein docked structures based on the balance and tightness of
      binding.
AB  - One main issue in protein-protein docking is to filter or score the putative
      docked structures. Unlike many popular scoring functions that are based on
      geometric and energetic complementarity, we present a set of scoring functions
      that are based on the consideration of local balance and tightness of binding of
      the docked structures. These scoring functions include the force and moment
      acting on one component (ligand) imposed by the other (receptor) and the second
      order spatial derivatives of protein-protein interaction potential. The scoring
      functions were applied to the docked structures of 19 test targets including
      enzyme/inhibitor, antibody/antigen and other classes of protein complexes. The
      results indicate that these scoring functions are also discriminative for the
      near-native conformation. For some cases, such as antibody/antigen, they show
      more discriminative efficiency than some other scoring functions, such as
      desolvation free energy (deltaG(des)) based on pairwise atom-atom contact energy
      (ACE). The correlation analyses between present scoring functions and the
      energetic functions also show that there is no clear correlation between them;
      therefore, the present scoring functions are not essentially the same as energy
      functions.

PMID- 15562990
TI  - PLASS: protein-ligand affinity statistical score--a knowledge-based force-field
      model of interaction derived from the PDB.
AB  - We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise
      potential of mean-force for rapid estimation of the binding affinity of a ligand
      molecule to a protein active site. This scoring function is derived from the
      frequency of occurrence of atom-type pairs in crystallographic complexes taken
      from the Protein Data Bank (PDB). Statistical distributions are converted into
      distance-dependent contributions to the Gibbs free interaction energy for 10
      atomic types using the Boltzmann hypothesis, with only one adjustable parameter.
      For a representative set of 72 protein-ligand structures, PLASS scores correlate
      well with the experimentally measured dissociation constants: a correlation
      coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results
      from our novel treatment of the volume correction term, which takes into account
      the inhomogeneous properties of the protein-ligand complexes. PLASS is able to
      rank reliably the affinity of complexes which have as much diversity as in the
      PDB.

PMID- 15562991
TI  - ProteinShop: a tool for interactive protein manipulation and steering.
AB  - We describe ProteinShop, a new visualization tool that streamlines and simplifies
      the process of determining optimal protein folds. ProteinShop may be used at
      different stages of a protein structure prediction process. First, it can create
      protein configurations containing secondary structures specified by the user.
      Second, it can interactively manipulate protein fragments to achieve desired
      folds by adjusting the dihedral angles of selected coil regions using an Inverse
      Kinematics method. Last, it serves as a visual framework to monitor and steer a
      protein structure prediction process that may be running on a remote machine.
      ProteinShop was used to create initial configurations for a protein structure
      prediction method developed by a team that competed in CASP5. ProteinShop's use
      accelerated the process of generating initial configurations, reducing the time
      required from days to hours. This paper describes the structure of ProteinShop
      and discusses its main features.

PMID- 15562992
TI  - Docking and scoring of metallo-beta-lactamases inhibitors.
AB  - The performance of the AutoDock, GOLD and FlexX docking programs was evaluated
      for docking of dicarboxylic acid inhibitors into metallo-beta-lactamases (MBLs).
      GOLD provided the best overall performance, with RMSDs between experimental and
      docked structures of 1.8-2.6 A and a good correlation between the experimentally
      determined MBL-inhibitor affinities and the GOLD scores. GOLD was selected for a
      test including a broad spectrum of inhibitors for which experimental MBL
      inhibitor binding affinities are available. This study revealed that (1) for most
      compound classes (dicarboxylic acids, tetrazoles, sulfonylhydrazones, and peptide
      like compounds) there is a good correlation between the experimentally determined
      MBL-inhibitor affinities and the GOLD scores, (2) the correlation only holds
      within a given class, that is, scores of compounds from different classes cannot
      be directly compared, (3) for some compound classes (e.g. small sulphur
      compounds) there is no direct correlation between the experimentally determined
      MBL-inhibitor affinities and the GOLD scores. Using partial least squares
      methods, a model with R2 = 0.82 and Q2 = 0.78 for the training set was obtained
      based on the GOLD score and descriptors associated with binding of the IMP-1
      inhibitors to the enzyme. The external Q2 for the test set is 0.73. This final
      model for prediction of IMP-1 MBL-inhibitor affinity handled all known classes of
      MBL-inhibitors, except small sulphur compounds.

PMID- 15562993
TI  - Definition, objectives, and evaluation of natural attenuation.
AB  - Natural attenuation offers large benefits to owners and managers of contaminated
      sites, but often raises strong objections from those who live and work near a
      site and are asked to assume most of the long-term risks. Part of the controversy
      comes about because published definitions of natural attenuation do not identify
      a realistic end-point objective, and they also are ambiguous about the naturally
      occurring processes that can achieve the objective. According to guidance from
      the U.S. National Research Council (NRC 2000), destruction and strong
      immobilization are the naturally occurring processes that achieve a realistic
      objective: containing the contaminant relatively nears its source, thereby
      minimizing exposure risks. The strategy for obtaining solid evidence that the
      objective is being achieved requires measurements that establish a cause-and
      effect relationship between contaminant loss and a destruction or strong
      immobilization reaction. The cause-and-effect relationship is best documented
      with reaction footprints, which typically are concentration changes in reactants
      or products of the destruction or immobilization reaction. MTBE presents a
      contemporary example in which footprint evidence for biodegradation is especially
      crucial, since aerobic biodegradation of MTBE requires special conditions not
      present at all sites: a high availability of dissolved oxygen and bacteria
      expressing particular oxygenase enzymes.

PMID- 15562994
TI  - Challenges in monitoring the natural attenuation of spatially variable plumes.
AB  - Monitored natural attenuation may be applied as a risk-based remediation strategy
      if it can be established that contaminants are or will be reduced to some
      acceptable level at or before a compliance point. Contaminant attenuation is
      often attributed to intrinsic biodegradation, which in some circumstances may
      occur only at the plume fringes where electron acceptors from the surrounding
      uncontaminated zones mix by dispersion and diffusion with the plume. However, due
      to the common spatial and temporal variability exhibited by many plumes, the
      centreline monitoring approaches advocated in many natural attenuation protocols
      may be unable to detect natural attenuation occurring primarily by fringe
      processes. Snapshot data from a multilevel sampling well transect across an MTBE
      plume at Vandenberg Air Force Base, CA, USA, illustrate the difficulty of
      centreline monitoring and the challenge of providing sufficient detail to detect
      attenuation processes that may be occurring primarily at plume fringes. In a
      study of a phenols plume in Wolverhampton, UK, high-resolution multilevel wells
      demonstrated that the key biodegradation processes were restricted spatially to
      the upper fringe of the plume and were rate-limited by transverse dispersion and
      diffusion of electron acceptors into the plume. Thus the overall extent of
      biodegradation was considerably less than suggested by a plume-scale analysis of
      total electron acceptor and contaminant budgets. These examples indicate that
      more robust and cost-effective MNA assessments can be obtained using monitoring
      strategies that focus on the location of key biodegradation processes.

PMID- 15562995
TI  - Monitored natural attenuation of chlorinated solvents: assessment of potential
      and limitations.
AB  - Chlorinated solvent contaminations in groundwater and soil are a widespread
      problem. Their remediation either by active and/or passive measures is
      complicated though, due to their characteristic features of long plumes and
      DNAPL. In this study Monitored Natural Attenuation (MNA) is evaluated regarding
      its applicability to remediate chlorinated solvent sites. At first a short
      overview of legal requirements is given, by whose means the efficiency of MNA is
      supposed to be demonstrated and assessed. Thereby the focus is set on the
      circumstances in the United States and Germany, as in the first MNA is applied as
      remediation option, whereas in the latter implementation and definition of MNA is
      under discussion. Based on criteria given by several German guidelines
      investigation methods and suitable parameters are discussed with the objective to
      evaluate their potential and limitations to demonstrate MNA at a chlorinated
      solvent site. Regarding the description of source location/inventory and source
      emission the legal requirements cannot be accomplished mainly because of missing
      methods. With regard to the characterization of plume migration, and evaluation
      of the efficiency of NA processes the combination of hydrogeochemical data and
      model approaches can accomplish most of the legal requirements. Applicability of
      microbiological and isotope methods is limited which is also reflected by
      evaluation of field studies, where these methods have been used at less than 10%
      of the sites. With regard to chlorinated solvents current German guidelines
      should be modified to enable the feasible application of MNA as an alternative or
      additional remediation option.

PMID- 15562996
TI  - Long-term sustainability of reductive dechlorination reactions at chlorinated
      solvents sites.
AB  - The sustainability of biodegradation reactions is of interest at Type 1
      chlorinated solvent sites where monitored natural attenuation is being considered
      as a remedial alternative. Type 1 chlorinated solvent sites are sites undergoing
      reductive dechlorination where anthropogenic substrates (such as landfill
      leachate or fermentable organics in the waste materials) ferment to produce
      hydrogen, a key electron donor. A framework is provided that classifies Type 1
      chlorinated solvent sites based on the relative amounts and the depletion rates
      of the electron donors and the electron acceptors (i.e., chlorinated solvents).
      Expressions are presented for estimating the total electron donor demand due to
      the presence of solvents and competing electron acceptors such as dissolved
      oxygen, nitrate, and sulfate. Finally, a database of 13 chlorinated solvent sites
      was analyzed to estimate the median and maximum mass discharge rate for dissolved
      oxygen, nitrate, and sulfate flowing into chlorinated solvent plumes. These
      values were then used to calculate the amount of hydrogen equivalents and
      potential for lost perchloroethylene (PCE) biodegradation represented by the
      inflow of these competing electron acceptors. The median and maximum mass of PCE
      biodegradation lost due to competing electron acceptors, assuming 100%
      efficiency, was 226 and 4621 kg year(-1), respectively.

PMID- 15562997
TI  - Complete biological dehalogenation of chlorinated ethylenes in sulfate containing
      groundwater.
AB  - The ability of dehalogenating bacteria to compete with sulfate reducing bacteria
      for electron donor was studied in microcosms that simulated groundwater
      contaminated with both chlorinated ethylenes and fuel hydrocarbon compounds.
      Results demonstrate that reductive dehalogenation of perchloroethylene to
      ethylene can proceed in the presence of > 100 mg l(-1) sulfate. The hydrogen
      concentration, which was 2.5 nM in the presence of approximately 150 mg l(-1)
      sulfate and in the absence of chlorinated compounds, decreased to 0.7 nM during
      the dechlorination of trichloroethylene and increased to 1.6 nM during the
      dechlorination of cis-dichloroethylene and vinyl chloride. With only sediment
      associated donor ("historical" donor) present, dechlorination of
      trichloroethylene proceeded slowly to ethylene (on a time scale of several
      years). Addition of toluene, a model hydrocarbon compound, stimulated
      dechlorination indirectly. Toluene degradation was rapid and linked to sulfate
      utilization, and presumably formed fermentable substrates that served as hydrogen
      donors. Dehalogenation was inhibited in soil free microcosms containing 5 mM
      sulfide, but inhibition was not observed when either aquifer sediment or 5 mM
      ferrous chloride was added.

PMID- 15562998
TI  - Modeling intrinsic bioremediation for interpret observable biogeochemical
      footprints of BTEX biodegradation: the need for fermentation and abiotic chemical
      processes.
AB  - The intrinsic bioremediation of BTEX must be documented by the stoichiometric
      consumption and production of several other compounds, called 'footprints' of the
      biodegradation reaction. Although footprints of BTEX biodegradation are easy to
      identify from reaction stoichiometry, they can be confounded by the stepwise
      nature of the biodegradation reactions and by several abiotic chemical reactions
      that also produce or consume the footprints. In order to track the footprints for
      BTEX biodegradation, the following reactions need to be considered explicitly:
      (1) fermentation and methanogenesis as separate processes, (2) precipitation and
      dissolution of calcite, (3) precipitation and dissolution of amorphous iron
      monosulfide (FeS), (4) conversion of FeS into the thermodynamically stable pyrite
      (FeS2) with loss of sulfide and abiotic formation of H2, and (5) reductive
      dissolution of solid iron(III) by oxidation of sulfide. We critically review the
      research that underlies why these mechanisms must be included and how to describe
      them quantitatively. A companion manuscript develops and applies a mathematical
      model that includes these reactions.

PMID- 15562999
TI  - Formulation of the CBC-model for modelling the contaminants and footprints in
      natural attenuation of BTEX.
AB  - This paper provides the details of the Coupled Biological and Chemical (CBC)
      model for representing in situ bioremediation of BTEX. The CBC model contains
      novel features that allow it to comprehensively track the footprints of BTEX
      bioremediation, even when the fate of those footprints is confounded by abiotic
      reactions and complex interactions among different kinds of microorganisms. To
      achieve this comprehensive tracking of all the footprints, the CBC model contains
      important new biological features and key abiotic reactions. The biological
      module of the CBC-model includes these important new aspects: (1) it separates
      BTEX fermentation from methanogenesis, (2) it explicitly includes biomass as a
      sink for electrons and carbon, (3) it has different growth rates for each biomass
      type, and (4) it includes inhibition of the different reactions by other electron
      acceptors and by sulfide toxicants. The chemical module of the CBC-model includes
      abiotic reactions that affect the footprints of the biological reactions. In
      particular, the chemical module describes the precipitation/dissolution of CaCO3,
      Fe2O3, FeS, FeS2, and S degrees. The kinetics for the precipitation/dissolution
      reactions follow the critical review in Maurer & Rittmann (2004).

PMID- 15563000
TI  - Modeling natural attenuation of chlorinated ethenes under spatially varying redox
      conditions.
AB  - A three-dimensional model for the transport and reductive dechlorination of
      chlorinated ethenes in ground-water systems with variable redox conditions is
      demonstrated and applied to a pilot test for accelerated natural attenuation of
      trichloroethene (TCE). The rate and extent of biotransformation of TCE and
      chlorinated progeny is controlled by the dominant terminal electron accepting
      process (TEAP) that is simulated over space and time. The solute transport code,
      Sequential Electron Acceptor Model, 3D-transport, (SEAM3D) which simulates
      aerobic and sequential anaerobic biodegradation of organic carbon, is modified to
      implement the equations. Results of a generic model for TCE transport in ground
      water systems with different redox conditions demonstrate that the degree of
      chlorinated ethene attenuation is influenced by background concentrations of
      aqueous- and solid-phase electron acceptors, but that model results are sensitive
      to other input parameters (inhibition coefficients, maximum rate of reductive
      dechlorination, biomass concentrations, and ground-water velocity). Simulation
      results of enhanced in situ bioremediation using dissolved organic carbon as a
      reducing agent show that spatial and temporal changes in the dominant TEAP and
      the subsequent rate of reductive dechlorination are adequately represented with
      the model. Initial concentrations of Fe(III) and the dechlorinating microbial
      population influence the simulated time lag observed during the pilot test.

PMID- 15563001
TI  - Evaluation of exploration and monitoring methods for verification of natural
      attenuation using the virtual aquifer approach.
AB  - Though natural attenuation (NA) is increasingly considered as a remediation
      technology, the methods for proper identification and quantification of NA are
      still under discussion. Here the "Virtual Aquifer" approach is used to
      demonstrate problems which may arise during measurement of concentrations in
      observation wells and for interpolation of locally measured concentrations in
      contaminated heterogeneous aquifers. The misinterpretation of measured
      concentrations complicates the identification and quantification of natural
      attenuation processes. The "Virtual Aquifer" approach accepts the plume simulated
      with a numerical model for a heterogeneous aquifer as "virtual reality". This
      virtual plume is investigated in the model with conventional methods like
      observations wells. The results of the investigation can be compared to the
      virtual "reality", evaluating the monitoring method. Locally determined
      concentrations are interpolated using various interpolation methods and different
      monitoring set-ups. The interpolation results are compared to the simulated plume
      to evaluate the quality of interpolation. This evaluation is not possible in
      nature, since concentrations in a heterogeneous aquifer are never known in
      detail.

PMID- 15563002
TI  - Legal aspects of natural attenuation in Germany.
AB  - The legal aspects of Natural Attenuation are multifarious. Therefore, the
      specific legal situation in Germany shall be described in the following as an
      example of the classification of NA in an European country. Additionally, a short
      reference to the international dimension of NA is included at the end. The
      article is meant to introduce the reader to the ongoing legal discussion in
      Germany. A comprehensive legal examination will be part of the final report of
      the so-called 'KORA' project (Natural Attenuation: Retention and Degradation
      Processes Reducing Contaminations in Groundwater and Soil) funded by the German
      Federal Ministry of Education and Research. The authors participate in this
      project as coordinator for legal affairs. The final report is expected in 2006.

PMID- 15563003
TI  - Biodegradation of PCE and TCE in landfill leachate predicted from concentrations
      of molecular hydrogen: a case study.
AB  - The Refuse Hideaway Landfill (23-acre) received municipal, commercial, and
      industrial waste between 1974 and 1988. It was designed as a "natural
      attenuation" landfill and no provision was made to collect and treat contaminated
      water. Natural biological degradation through sequential reductive dechlorination
      had been an important mechanism for natural attenuation at the site. We used the
      concentration of hydrogen to forecast whether reductive dechlorination would
      continue over time at particular locations in the plume. Based on published
      literature, reductive dechlorination and natural attenuation of PCE, TCE, and cis
      DCE can be expected in the aquifer if the concentration of molecular hydrogen in
      monitoring wells are adequate (> 1 nanomolar). Reductive dechlorination can be
      expected to continue as the ground water moves down gradient. Natural attenuation
      through reductive dechlorination is not expected in flow paths that originate at
      down gradient monitoring wells with low concentrations of molecular hydrogen (< 1
      nanomolar). In three monitoring wells at the margin of the landfill and in five
      monitoring wells down gradient of the landfill, ground water maintained a
      molecular hydrogen concentration, ranging from 1.30 to 9.17 nanomolar, that is
      adequate for reductive dechlorination. In three of the monitoring wells far down
      gradient of the landfill, the concentration of molecular hydrogen (0.33 to 0.83
      nanomolar) was not adequate to support reductive dechlorination. In wells with
      adequate concentrations of hydrogen, the concentrations of chlorinated volatile
      organic compounds were attenuated over time, or concentrations of chlorinated
      volatile organics were below the detection limit. In wells with inadequate
      concentrations of hydrogen, the concentrations of chlorinated organic compounds
      attenuated at a slower rate over time. In wells with adequate hydrogen the first
      order rate of attenuation of PCE, TCE, cis-DCE and total chlorinated volatile
      organic compounds varies from 0.38 to 0.18 per year. In wells without adequate
      hydrogen the rate varies from 0.015 to 0.006 per year.

PMID- 15563004
TI  - Development of a whole body physiologically based model to characterise the
      pharmacokinetics of benzodiazepines. 1: Estimation of rat tissue-plasma partition
      ratios.
AB  - Three methods for estimation of the equilibrium tissue-to-plasma partition ratios
      (Kp values) in the presence of tissue concentration time data have been
      investigated. These are the area method, the open loop (tissue specific) method
      and the whole body model(closed loop) method, each with different model
      assumptions. Additionally, multiple imputations, a technique for dealing with
      deficiencies in data sets (i.e., missing tissues) is used. The estimated Kp
      values by the three methods have been compared and the limitations and advantages
      of each approach drawn. The area method, which is essentially model free, gives
      only a crude estimate of Kp without making any statement of its uncertainty;
      whereas both the open and closed loop methods provide an estimate of this. The
      closed loop method, where the most assumptions are made, is the approach that
      gives the best overall estimates of Kp, which was confirmed by comparing the
      predicted concentration-time profiles with experimental data. Although the
      estimates from the closed loop method, as well as the other two methods, are
      conditioned on the data, they are the most reliable for both propagating
      parameter variability and uncertainty through a whole body physiologically based
      model, as well as for extrapolation to human. A series of benzodiazepines, namely
      alprazolam, chlordiazepoxide, clobazam, diazepam, flunitrazepam, midazolam and
      triazolam in rat is used as a case study in the current investigation.

PMID- 15563005
TI  - Estimating bias in population parameters for some models for repeated measures
      ordinal data using NONMEM and NLMIXED.
AB  - The application of proportional odds models to ordered categorical data using the
      mixed-effects modeling approach has become more frequently reported within the
      pharmacokinetic/pharmacodynamic area during the last decade. The aim of this
      paper was to investigate the bias in parameter estimates, when models for ordered
      categorical data were estimated using methods employing different approximations
      of the likelihood integral; the Laplacian approximation in NONMEM (without and
      with the centering option) and NLMIXED, and the Gaussian quadrature
      approximations in NLMIXED. In particular, we have focused on situations with non
      even distributions of the response categories and the impact of interpatient
      variability. This is a Monte Carlo simulation study where original data sets were
      derived from a known model and fixed study design. The simulated response was a
      four-category variable on the ordinal scale with categories 0, 1, 2 and 3. The
      model used for simulation was fitted to each data set for assessment of bias.
      Also, simulations of new data based on estimated population parameters were
      performed to evaluate the usefulness of the estimated model. For the conditions
      tested, Gaussian quadrature performed without appreciable bias in parameter
      estimates. However, markedly biased parameter estimates were obtained using the
      Laplacian estimation method without the centering option, in particular when
      distributions of observations between response categories were skewed and when
      the interpatient variability was moderate to large. Simulations under the model
      could not mimic the original data when bias was present, but resulted in
      overestimation of rare events. The bias was considerably reduced when the
      centering option in NONMEM was used. The cause for the biased estimates appears
      to be related to the conditioning on uninformative and uncertain empirical Bayes
      estimate of interindividual random effects during the estimation, in conjunction
      with the normality assumption.

PMID- 15563006
TI  - Statistical issues in a modeling approach to assessing bioequivalence or PK
      similarity with presence of sparsely sampled subjects.
AB  - Drug development at different stages may require assessment of similarity of
      pharmacokinetics (PK). The common approach for such assessment when the
      difference is drug formulation is bioequivalence (BE), which employs a hypothesis
      test based on the evaluation of a 90% confidence interval for the ratio of
      average pharmacokinetic (PK) parameters. The role of formulation effect in BE
      assessment is replaced by subject population in PK similarity assessment. The
      traditional approach for BE requires that the PK parameters, primarily AUC and
      Cmax, be obtained from every individual. Unfortunately in many clinical
      circumstances, some or even all of the individuals may be sparsely sampled,
      making the individual evaluation difficult. In such cases, using models,
      particularly population models, becomes appealing. However, conducting an
      appropriate statistical test based on population modeling in a form consistent,
      at least in principle, with traditional 90% confidence interval approach is not
      so straightforward as it may appear. This manuscript proposes one such approach
      that can be applied to sparse sampling situations. The approach aims to maintain,
      as much as possible, the appropriateness of the hypothesis test. It is applied to
      data from clinical studies to address a need in drug development for assessment
      of PK similarity in different populations.

PMID- 15563007
TI  - Tuberous sclerosis complex: future research directions.

PMID- 15563008
TI  - Tuberous sclerosis complex: pathogenesis, diagnosis, strategies, therapies, and
      future research directions.

PMID- 15563009
TI  - Diagnosis of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex is a dominantly inherited disorder affecting multiple
      organs; because of its phenotypic variability, the diagnosis of tuberous
      sclerosis complex can be difficult in the young or in individuals with subtle
      findings. Recently revised consensus diagnostic criteria for tuberous sclerosis
      complex reflect an improved understanding of its clinical manifestations and its
      genetic and molecular mechanisms. The diagnostic criteria are based on the
      premise that there are probably no truly pathognomonic clinical signs for
      tuberous sclerosis complex; signs that were once regarded as specific occur as
      isolated findings in individuals with no other clinical or genetic evidence of
      tuberous sclerosis complex. Consequently, the revised criteria require tuberous
      sclerosis complex-associated lesions of two or more organ systems or at least two
      dissimilar lesions of the same organ to confirm the diagnosis. The addition of
      DNA testing complements clinical diagnosis and allows more precise genetic
      counseling and, in some individuals, prenatal diagnosis. Nevertheless, the 15%
      false-negative rate for DNA testing and the occurrence of germline mosaicism in
      about 2% of individuals with tuberous sclerosis complex make it difficult to
      exclude the diagnosis of tuberous sclerosis complex in family members.

PMID- 15563010
TI  - Brain abnormalities in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex is an autosomal dominant multisystem disorder.
      Spontaneous mutations occur in up to 60% of patients with gene loci located on
      chromosomes 9q34 (TSC1) and 16p13 (TSC2). Diagnosis is established with the
      identification of various neurocutaneous markers and multiple organ system
      hamartomas. The variable expression of severity, the potential for cognitive
      dysfunction, and epilepsy compound the clinical picture. The intracranial
      abnormalities include the identification of migration and hamartomatous brain
      lesions, such as tubers, subependymal nodules, and subependymal giant cell
      astrocytomas. A number of other neuroimaging and morphometric abnormalities
      coexist, which can be identified with current neuroimaging techniques. This
      review examines the spectrum of brain abnormalities encountered in tuberous
      sclerosis complex and presents them as not merely a collection of lesions but
      more cohesively in the context of a global neuronal migration disorder.

PMID- 15563011
TI  - Standardized whole brain mapping of tubers and subependymal nodules in tuberous
      sclerosis complex.
AB  - Tuberous sclerosis complex is associated with radiologically visible
      abnormalities of brain structure, principally tubers and subependymal nodules. We
      reviewed the literature on neuroimaging of tubers and subependymal nodules and
      found qualitative evidence of bilateral, predominantly frontal distribution of
      tubers and bilateral, predominantly subcortical distribution of subependymal
      nodules in prior studies of pediatric samples. We studied 25 high-functioning
      adults with tuberous sclerosis complex and normal IQ, acquiring both dual spin
      echo and fluid-attenuated inversion recovery magnetic resonance imaging sequences
      to optimize radiologic diagnosis of tubers and nodules. Individual lesion maps
      were then coregistered in a standard stereotactic space to facilitate
      construction of lesion density maps and estimation of lesion density in cortical
      and subcortical regions reliably defined by a parcellated template image. We
      found the highest frequency of tubers in frontal lobes and the highest density of
      tubers in parietal regions. There was significant regional variation in tuber
      density but no significant lateralization of frequently bilateral tubers. Nodules
      were located predominantly in the caudate nucleus and were not significantly
      lateralized. Tuber and nodule volumes were significantly positively correlated.
      Tuber volume was larger, on average, in patients with a lifetime history of
      epilepsy, but there was no correlation between IQ and these measures of lesion
      load. Contemporary image processing tools can be used to enhance quantitative,
      whole brain analysis of lesion load in patients with tuberous sclerosis complex.

PMID- 15563012
TI  - Behavioral and cognitive aspects of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex is a multisystem genetic disorder. Of all the possible
      manifestations of this complex disorder, the cognitive and behavioral problems
      represent the area of greatest concern to parents and caregivers. This review
      outlines the current evidence regarding global intellectual abilities, behavioral
      problems, psychiatric diagnoses, learning disorders, and specific
      neuropsychologic deficits for which individuals with tuberous sclerosis complex
      are at particularly increased risk, and outlines approaches to intervention.
      Approximately half of individuals diagnosed with tuberous sclerosis complex
      present with global intellectual impairment and developmental psychopathologies.
      Those with normal intellectual abilities are also at high risk of specific
      neuropsychologic deficits and behavioral, learning, and other psychiatric
      disorders. There is no evidence for an inevitable decline in cognition or
      behavior, and any such changes should be investigated. The evolving
      neurocognitive literature suggests that frontal brain systems might be most
      consistently disrupted by tuberous sclerosis complex-related neuropathology, thus
      leading to abnormalities in regulatory and goal-directed behaviors.

PMID- 15563013
TI  - Autism and tuberous sclerosis.
AB  - The co-occurrence of autism spectrum disorder and tuberous sclerosis complex has
      been recognized for decades. The prevalence of tuberous sclerosis complex in the
      autism spectrum disorder population is 1 to 4%, whereas features of autism
      spectrum disorder are present in 25 to 50% of individuals with tuberous sclerosis
      complex. The underlying reason for this association might be a nonspecific
      disruption of brain function owing to tuberous sclerosis complex, including tuber
      location, seizures and their effect on brain development, cognitive impairment, a
      disturbance in brain development in regions associated with autism spectrum
      disorder, or, less likely, a linkage between a TSC gene and an autism
      susceptibility gene. Awareness of the relationship between autism spectrum
      disorder and tuberous sclerosis complex is important during the evaluation of
      individuals with either disorder. Better delineation of the association and its
      causative factors is needed for the development of possible interventions.

PMID- 15563014
TI  - Managing epilepsy in tuberous sclerosis complex.
AB  - Epilepsy is very common in tuberous sclerosis complex and occurs in 80 to 90% of
      affected individuals during their lifetime. Onset usually occurs during
      childhood, and up to one third of children with tuberous sclerosis complex will
      develop infantile spasms. Although not completely understood, the incidence of
      epilepsy is thought to relate to the neuropathologic features of the disorder,
      including cortical tubers and other dysgenetic features. Individuals with
      tuberous sclerosis complex frequently have epileptiform features to their
      electroencephalograms. Treatment of epilepsy in tuberous sclerosis complex is
      similar to epilepsy resulting from other causes and includes anticonvulsant
      medications, the vagus nerve stimulator, and the ketogenic diet. Vigabatrin has
      been shown to be particularly effective in treating infantile spasms in the
      setting of tuberous sclerosis complex. Epilepsy surgery has a very important role
      in the management of children and adults with pharmacoresistant epilepsy in
      tuberous sclerosis complex.

PMID- 15563015
TI  - Epilepsy surgery for children with tuberous sclerosis complex.
AB  - Tuberous sclerosis complex is associated with medically refractory seizures and
      developmental delay in children. These epilepsies are often resistant to
      antiepileptic drugs, can be quite severe, and usually have a negative impact on
      the child's neurologic and cognitive development. It is believed that functional
      outcome is improved if seizures can be controlled at an early age. The surgical
      treatment of intractable epilepsy in children and adults with tuberous sclerosis
      complex has gained significant interest in recent years. Previously published
      studies have shown a potential benefit from resection of single tubers, with most
      of the results noted in relatively older children. All of these reports support
      the idea that if a single primary epileptogenic tuber or region can be
      identified, then a surgical approach is appropriate. However, most children with
      tuberous sclerosis complex have multiple potentially epileptogenic tubers,
      rendering localization challenging, and they are therefore rejected as possible
      surgical candidates. We have used a novel surgical approach using invasive
      intracranial monitoring, which is typically multistaged and bilateral. This
      multistage surgical approach has been useful in identifying both primary and
      secondary epileptogenic zones in patients with tuberous sclerosis complex with
      multiple tubers. Multiple or bilateral seizure foci are not necessarily a
      contraindication to surgery in selected patients. Long-term follow-up will
      determine whether this approach has durable effects. We await better methods for
      identifying the epileptogenic zone, both noninvasive and invasive.

PMID- 15563016
TI  - Non-neurologic manifestations of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex is a heterogeneous genetic disorder affecting multiple
      organ systems at various points throughout the lifespan. Increasingly,
      neurologically asymptomatic adults are being diagnosed with tuberous sclerosis
      complex through renal or pulmonary presentations. Although chiefly recognized for
      its cerebral manifestations, understanding of the non-neurologic aspects of the
      disorder has advanced greatly in recent years, and they are reviewed here.

PMID- 15563017
TI  - Molecular genetic basis of tuberous sclerosis complex: from bench to bedside.
AB  - Tuberous sclerosis complex is an autosomal dominant disease of benign tumors
      occurring in multiple organ systems of the body. Either of two genes, TSC1 or
      TSC2, can be mutated, resulting in the tuberous sclerosis complex phenotype. The
      protein products of the tuberous sclerosis complex genes, hamartin (TSC1) and
      tuberin (TSC2), have been discovered to play important roles in several cell
      signaling pathways. Knowledge regarding the function of the tuberin-hamartin
      complex has led to therapeutic intervention trials. Numerous pathogenic mutations
      have been elucidated in individuals affected with tuberous sclerosis complex.
      Information on the type and distribution of nearly 1000 mutations in the two
      genes is discussed. Mosaicism for tuberous sclerosis complex mutations has been
      documented, complicating provision of genetic counseling to families. Emerging
      genotype-phenotype correlations should provide guidance for better medical care
      of individuals with tuberous sclerosis complex.

PMID- 15563018
TI  - Aberrant cellular differentiation and migration in renal and pulmonary tuberous
      sclerosis complex.
AB  - This review is focused on pathways and mechanisms that might provide molecular
      links between the pathogenesis of renal and pulmonary disease in tuberous
      sclerosis complex and the pathogenesis of the neurologic manifestations of
      tuberous sclerosis complex. Tuberous sclerosis complex is an autosomal dominant
      disorder in which the manifestations can include seizures; mental retardation;
      autism; benign tumors of the brain, retina, skin, and kidneys; and pulmonary
      lymphangiomyomatosis. Lymphangiomyomatosis is a life-threatening lung disease
      affecting almost exclusively young women. Genetic data have demonstrated that the
      cells giving rise to renal angiomyolipomas, the most frequent tumor type in
      patients with tuberous sclerosis complex, exhibit differentiation plasticity.
      Genetic studies have also shown that the benign smooth muscle cells of
      angiomyolipomas and pulmonary lymphangiomyomatosis have the ability to migrate or
      metastasize to other organs. These findings indicate that hamartin and tuberin
      play functional roles in the regulation of cell migration and differentiation.
      The biochemical pathways responsible for these effects are not yet fully
      understood but might involve dysregulation of the small guanosine triphosphatase
      Rho. Similar pathways might contribute to aberrant neuronal differentiation and
      migration in tuberous sclerosis complex.

PMID- 15563019
TI  - Molecular pathogenesis of tuber formation in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex results from mutations in the TSC1 (hamartin) and TSC2
      (tuberin) genes. Tubers are cortical developmental malformations in patients with
      tuberous sclerosis complex that are associated with intractable epilepsy and are
      composed of histologically distinct cell types, including giant cells and
      dysplastic neurons. We recently showed that tubers can be dynamic lesions
      characterized by populations of cells undergoing proliferation, migration, and
      death. We demonstrate that there is cell-specific activation of the mammalian
      target of rapamycin (mTOR)/p70S6 kinase/ribosomal S6 cascade in tubers and that
      giant cells express activated (phosphorylated) p70S6 kinase and ribosomal S6
      protein. These findings support impaired hamartin- and tuberin-mediated mTOR
      pathway regulation. Tubers likely form by constitutive activation of the mTOR
      cascade during brain development as a consequence of impaired hamartin or tuberin
      function.

PMID- 15563020
TI  - Mouse models of tuberous sclerosis complex.
AB  - The most devastating complications of tuberous sclerosis complex affect the
      central nervous system and include epilepsy, mental retardation, autism, and
      glial tumors. Mutations in one of two genes, TSC1 and TSC2, result in a similar
      disease phenotype by disrupting the normal interaction of their protein products,
      hamartin and tuberin, which form a functional signaling complex. Disruption of
      these genes in the brain results in abnormal cellular differentiation, migration,
      and proliferation, giving rise to characteristic brain lesions called cortical
      tubers. Relevant animal models, including conventional and conditional knockout
      mice, are valuable tools for studying the normal functions of tuberin and
      hamartin and how disruption of their expression gives rise to the variety of
      clinical features that characterize tuberous sclerosis complex. In the future,
      these animals will be invaluable preclinical models for the development of highly
      specific and efficacious treatments for children affected with tuberous sclerosis
      complex.

PMID- 15563021
TI  - Advances in tuberous sclerosis complex research: the October 1, 2003, Child
      Neurology Society Workshop.

PMID- 15563022
TI  - Spontaneous colibacillosis in infectious bursal disease-affected broiler flocks.

PMID- 15563023
TI  - Onchocerca cervicalis in horses from southern Brazil.
AB  - The objective of this study was to determine the occurrence of Onchocerca
      cervicalis in 1200 adult horses from rural areas of Rio Grande do Sul, Brazil.
      Umbilical skin specimens measuring 2 x 2 cm were minced, suspended in 10 ml of
      distilled water and incubated at room temperature overnight. The liquid volume
      was centrifuged and the sediment was screened for microfilariae. The ligamentum
      nuchae were totally removed, preserved in ice and dissected for the detection of
      adult forms of Onchocerca cervicalis. Microfilariae of Onchocerca cervicalis were
      detected in midventral skin biopsy samples in 215 (17.9%) of 1200 horses examined
      and the adult worms were recovered from 200 (16.6%) ligamentum nuchae from the
      same animals. These findings provide a basis for further studies to determine
      infection rates in horses from other regions of the state and to identify the
      intermediate host that transmits the disease.

PMID- 15563024
TI  - Effects of feeding maize stover and cottonseed cake on onset of puberty in Bunaji
      (Bos indicus) heifers.
AB  - A study was conducted to determine the influence of maize stover and cottonseed
      cake supplementation on age and live weight at onset of puberty in Bunaji
      heifers. A total of 49 pre-pubertal Bunaji heifers approximately 12 months of age
      were allotted randomly to one of two treatments of feed supplementation: (i)
      supplementation with maize stover and (ii) supplementation with cottonseed cake.
      The heifers were monitored for a period of 18 months for first observable oestrus
      or onset of puberty. The maize stover group were given maize stover (crop
      residue) supplementation ad libitum during the dry season; in the cottonseed cake
      group each heifer received 500 g of cottonseed cake per day during the dry
      season. The heifers supplemented with cottonseed cake attained puberty at an
      earlier age (23.9+/-1.2 months) than the heifers supplemented with maize stover
      (28.2+/-1.3 months; p<0.05). Similarly, heifers on the cottonseed cake
      supplementation attained puberty at a live weight of 270.5+/-3.5 kg; while the
      heifers on maize stover attained puberty at 237.6+/-5.8 kg (p <0.05). The
      cottonseed cake-supplemented heifers had higher daily gains than the maize stover
      supplemented heifers. It is concluded that provision of cottonseed cake as a
      supplement for heifers hastened the onset of puberty when compared to the maize
      stover supplemented heifers. Puberty can be achieved at an early age with
      improved nutrition and this can in turn reduce the generation interval and thus
      increase the rate of genetic gain of indigenous animals. Provision of protein
      supplements in cattle is recommended, especially in the tropics where marked
      seasonality of rainfall results in extremely poor pastures and herbage and low
      available protein.

PMID- 15563025
TI  - Mortality patterns in dairy animals under organized herd management conditions at
      Karnal, India.
AB  - Mortality patterns of two Zebu cattle breeds, Sahiwal and Tharparkar, and two
      crossbred strains, Karan Swiss and Karan Fries, maintained at the National Dairy
      Research Institute, Karnal were studied. Nine-year (1989--90 to 1997--98) data on
      mortality were analysed for year, season, age and cause effects on mortality
      rate. The overall mortality was 14.17%. The mortality in Sahiwal, Tharparkar,
      Karan Swiss and Karan Fries averaged 14.35%, 7.21%, 17.12% and 13.46%,
      respectively. The breed mortality rate did not vary significantly between years,
      seasons, age categories and causes of disease. However, the trends indicated
      appreciable difference in mortality rates. The mortality was highest in the year
      1994--95 (19.53%) and lowest in 1991--92 (8.56%). There was very little variation
      in seasonal mortality rate and mortality rate averaged 4.53%, 4.81% and 4.84% in
      hot-dry (March-June), hot-humid (July-October) and cold (November-February)
      seasons, respectively. The mortality up to 2 months of age accounted for a major
      share (50-60% or higher) in different breed groups. Digestive problems followed
      by respiratory disorders together accounted for 70-80% of total deaths.

PMID- 15563026
TI  - Growth performance and nutrient utilization in male and female Mithun calves on
      green forage-based diet.
AB  - A comparative study of growth rate and feed intake and its utilization in male
      and female Mithun calves was carried out in hilly tracts of Nagaland. The animals
      of both sexes were fed fresh jungle grasses ad libitum and 2.0 kg of rice bran
      fortified with 1% mineral mixture and 1% salt daily. Growth rates of 369.50 and
      305.67 g/day were observed in male and female calves, respectively. Sex-related
      differences in feed and nutrient intakes were statistically significant, whereas
      no significant difference was found in digestibility coefficients of nutrients
      between the groups as well as among the animals. Dry matter, digestible crude
      protein and total digestible nutrient intakes were recorded to be 107.81, 8.08
      and 74.73 g/kgW0.75 per day, respectively, irrespective of sex. Feed conversion
      efficiency (FCE) and nutritive value of the ration were similar in both male and
      female calves. Results obtained from the study indicate that the growth rate and
      nutrient intakes were higher in male than female calves but the sex of the animal
      did not have any significant effect on nutrient utilization.

PMID- 15563027
TI  - Survival analysis of calves and reproductive performance of cows in commercial
      dairy farms in and around Addis Ababa, Ethiopia.
AB  - A study was conducted at five locations to determine the survival rate of calves
      and to estimate the performance level of improved dairy cows under commercialized
      farming systems in Ethiopia. Seven hundred and one calves born from 1997 to 1999,
      and 797 cows were included in the study. Cumulative calf/heifer survival at 360,
      540 and 720 days was 80%, 76% and 70%, respectively. Number of services per
      conception averaged 2 while mean age at first service and days open were 850+/-18
      and 192+/-11 days, respectively. Calf survival, days open and age at first
      service were significantly affected by breed and management factors (p <0.05),
      whereas parity significantly affected the number of services per conception and
      days open. There was a tendency towards improved performance over the years. This
      was especially so for calf survival and days open. Clearly, all the traits
      measured varied among study farms, indicating that substantial improvement can be
      achieved through better management. This paper describes these individual traits
      of improved dairy breeds under commercialized farming systems in Ethiopia.

PMID- 15563028
TI  - Estimation of milk production from smallholder dairy cattle in the coastal
      lowlands of Kenya.
AB  - A study was carried out on 92 smallholder farms in Kwale district in Coast
      Province of Kenya to estimate the milk yield. The effect of concentrate feed
      supplementation on milk yield was also evaluated. Data were collected during a
      one-year observational longitudinal study. Analysis was done for 371 observations
      following 63 calving events. The mean annual milk offtake was estimated at 2021
      kg/cow. Forty-nine (77.8%) of the lactating cows were supplemented with
      concentrate feeds at varying rates of 0.5-3.0 kg/cow per day. Supplementary
      feeding of lactating cows led to a significantly higher mean daily milk yield
      compared to non-supplemented cows throughout the year (p < 0.05). The mean annual
      milk offtake from supplemented cows (2195 kg/cow) was 18.6% more than offtake
      from non-supplemented cows, a difference that was statistically significant (p <
      0.05). Therefore, supplementary feeding of commercial feed concentrates was a
      rational management practice. It was also concluded that milk production from
      smallholder dairy cows in the coastal lowlands of Kenya was comparable to that
      from similar production systems but lower than national targets.

PMID- 15563029
TI  - Effect of heat stress on milk production, rectal temperature, respiratory rate
      and blood chemistry in Holstein, Jersey and Australian Milking Zebu cows.
AB  - The effect of heat stress on changes in milk production, rectal temperature,
      respiratory rate and blood chemistry was evaluated in three groups of six mature
      Holstein, Jersey and Australian Milking Zebu (AMZ) dairy cows. These animals were
      subjected to a cool environment when the mean temperature-humidity index (THI)
      was 72+/-1.4 (dry bulb temperature of 22.2-24.4 degrees C and relative humidity
      of 100-60%) during the month of December. This experiment was repeated during the
      hotter month of July of the following year, when the mean THI was 93+/-3.1 (dry
      bulb temperature of 35.6-43.9 degrees C and relative humidity 95-35%). Holstein
      cows produced more (p <0.01) milk than AMZ and Jersey cows during the cooler
      months of the year and all the cows were dry during the hotter months from June
      until September. Heat stress increased (p<0.01) rectal temperature and
      respiratory rate in all three breeds. Heat stress had no effect on blood pH in
      Holstein and AMZ cows but lowered (p <0.01) blood pH from 7.42 to 7.34 in Jersey
      cows. In addition, heat stress lowered (p <0.01) blood pCO2 (kPa), bicarbonate
      (HCO3, mmol/L), base excess (BE, mmol/L) and plasma chloride (Cl-, mmol/L) in all
      three breeds. The total haemoglobin (THb, g/dl) was elevated (p <0.01) in all
      three breeds when they were subjected to heat stress. Heat stress increased
      (p<0.01) oxygen saturation (O2SAT, %) in Jersey and AMZ cows but lowered it (p
      <0.01) in Holstein cows. On the other hand, heat stress increased (p <0.01)pO2
      (kPa) in Holstein and Jersey cows but lowered it (p <0.01) in AMZ cows. Heat
      stress increased (p <0.01) plasma potassium (K, mmol/L) and calcium (Ca, mmol/L)
      only in Holstein and Jersey cows but lowered them (p<0.01) in AMZ cows. The
      plasma glucose (GLU, mmol/L) increased (p<0.01) with heat stress in Holstein and
      AMZ cows but decreased (p <0.01) in Jersey cows. Heat stress increased (p<0.01)
      plasma creatinine (CR, (mol/L) but lowered (p<0.01) plasma creatinine
      phosphokinase (CPK, IU/L), aspartate aminotransferase (AST, IU/L) and blood urea
      nitrogen (BUN, mmol/L) in all three breeds. These results indicate that heat
      stressed Holstein and AMZ cows were able to maintain their acid-base balance with
      a marginal change in their pH of 0.02 when their rectal temperatures increased by
      0.47 and 0.38 degrees C, respectively. When heat stress increased the rectal
      temperature in Jersey cows by 0.70 degrees C, the pH decreased (p<0.01) from 7.42
      to 7.34. However, even with this decrease 0.08 the pH is still within the lower
      physiological limit of 7.31.

PMID- 15563030
TI  - Study on coccidiosis of scavenging indigenous chickens in Central Ethiopia.
AB  - An investigation was made into coccidiosis of 190 scavenging indigenous chickens
      between September 2000 and April 2001 in three selected agroclimatic zones, in
      central Ethiopia. This was done through clinical, postmortem and microscopic
      examinations. Data were processed by chi-square and Mantel-Haenzel test. The
      study indicated that 25.8% (49/190) of the chickens were infected with
      coccidiosis and found to harbour one to four different species of Eimeria. Of
      these infected chickens, 30 (15.8%) and 19 (10.0%) were positive for clinical and
      sub-clinical coccidiosis, respectively. There was a significant altitude
      difference (chi2 = 14.7, p <0.001) in coccidiosis prevalence: 42.2% in chickens
      from highland region followed by 21.5% in mid-altitude and 13.1% in low-altitude
      areas. When quantified, the prevalence of coccidiosis was 2.66 and 4.83 times
      higher in the high-altitude than in mid-altitude (odds ratio, OR = 2.66, p<0.05)
      and low-altitude (OR = 4.83, p<0.001) chickens. The pathogenic Eimeria species
      responsible for clinical coccidiosis were E. necatrix, E. acervulina, E. maxima
      and E. tenella. With increasing demand for poultry products in developing
      countries, knowledge of production constraints in traditional management
      practices could help devise control strategies for constraints on backyard
      poultry production systems.

PMID- 15563031
TI  - Effects of energy and protein supplementation on the production and economic
      efficiency of scavenging improved (Tamhoang) and local (Ri) breed hens under
      smallholder conditions in Northern Vietnam.
AB  - The objectives of this study were to evaluate the effects of supplementing maize
      meal and soybean meal, separately or mixed, on egg production performance of two
      breeds of scavenging hens under on-farm conditions. Treatments were: (1)
      confined, with a mixed feed (75% maize meal and 25% soybean meal) ad libitum
      (CMF); (2) scavenging, with a supplement of 60 g/bird per day of maize meal
      (ScM); (3) scavenging, with a supplement of 25 g/bird per day of soybean meal
      (ScS); (4) scavenging, with 54 g/ bird per day of the mixed feed (ScMF). Mean hen
      day production was 21.8%, 19.8%, 17.7% and 22.8% for the CMF, ScM, ScS and ScMF
      treatments, respectively (p <0.05), and was significantly (p <0.001) higher for
      the improved Tamhoang breed (24.4%) than for the local Ri hens (16.7%). Mean egg
      weight was significantly higher for the Tamhoang (53.2 g) compared to the Ri hens
      (45.0 g) (p<0.01). Feed consumption per kilogram of eggs was significantly higher
      for the CMF treatment compared to the other treatments and was lower for the ScS
      compared to the other scavenging treatments (p <0.05). Feed cost per kilogram of
      eggs was lowest for the ScM treatment and was 30 to 40% higher for the confined
      treatment compared to the scavenging treatments. Feed consumption and cost of
      feed per kilogram of eggs were significantly lower for the Tamhoang than for the
      Ri hens.

PMID- 15563032
TI  - An evaluation of brewery waste as a replacement for concentrates in diets for
      growing crossbred common ducks.
AB  - An experiment was carried out to determine the effect of feeding brewery waste
      that replaced different levels of concentrate in diets for growing crossbred
      common ducks. A total of 300 ducks at 3 weeks of age were allocated in a 2 x 5
      factorial experiment. Two feeding systems were compared, with the brewery waste
      provided separately (S) or mixed (M) with a concentrate. For the first feeding
      system the concentrate was fed alone (C100M), or replaced successively by brewery
      waste at ratios of concentrate to brewery waste: 75:25 (C75M), 50:50 (C50M) and
      25:75 (C25M) on a dry matter basis, and fed ad libitum. For the second system
      concentrate and brewery waste were fed separately, with the same levels as in the
      first system. Total feed intakes for both feeding systems and intakes of brewery
      waste, total dry matter, crude protein, calcium and phosphorus increased
      significantly as concentrate was reduced (p <0.05). Daily weight gains were not
      significantly different between the two feeding systems, but were significantly
      lower for the C25 and C0 diets (p <0.05). Replacement of 50% of the concentrate
      by brewery waste resulted in the best growth performance. The highest net profits
      were from the separate feeding system, and for ducks fed brewery waste only (C0).
      It is concluded that brewery waste can replace traditional diets for crossbred
      common ducks based on concentrate.

PMID- 15563033
TI  - Friends, porn, and punk: sensation seeking in personal relationships, internet
      activities, and music preference among college students.
AB  - One hundred thirty-eight college students completed a questionnaire assessing
      level of sensation seeking, number of close and casual friends, Internet usage,
      liking certain styles of music, and genre of music listened to most often. It was
      found that the number of casual and close friends was positively associated with
      sensation seeking. Individuals who reported using the Internet to get sex
      oriented material, download or play music, play games, and chat/instant message
      with friends in the previous 24 hours had higher levels of sensation seeking.
      Liking punk, heavy metal, and reggae music were related to higher levels of
      sensation seeking. Higher sensation seeking was also associated with spending
      more time listening to punk music.

PMID- 15563034
TI  - The impact of cultural context on Brazilian adolescents' sexual practices.
AB  - AIDS prevention research has demonstrated that theoretically driven HIV
      prevention programs can be tailored to specific cultures. Further, condom self
      efficacy and contraceptive self-efficacy scales have been tested in the U.S. and
      been shown to predict condom and contraceptive use. Results of condom and
      contraceptive self-efficacy studies have been used to suggest ways to educate and
      counsel young people to avoid unprotected sex. This paper reports the findings
      from our research in Salvador, Brazil, using Levinson's Condom Self-Efficacy
      Scale (CDSE). The data are derived from six focus groups totaling 76 teenagers
      from three high schools. The focus group discussions explored cultural and
      psychological issues involved in condom use. Here we report on the gender
      dynamics of condom use as revealed by these urban Brazilian teenagers. Three
      focal points for behavioral change are identified: (1) issues of masculinity, (2)
      issues of femininity, and (3) condom use skills.

PMID- 15563035
TI  - Avenues to prestige among adolescents in public and religiously affiliated high
      schools.
AB  - We used data from 1,733 college students to explore whether adolescents' avenues
      to prestige differ in public and private high schools. Students attending seven
      large universities during the 1997--98 academic year provided information on the
      ways in which adolescents in their high schools had gained prestige with peers.
      The analyses revealed no differences by high school type for girls, with the
      exception of greater emphasis on clothes in public schools as compared with
      private schools. For boys, the differences were more pronounced. Boys who
      attended private schools were less likely than those who attended public schools
      to accrue prestige through clothes and car ownership and more likely to gain
      prestige through general sociability and having a good reputation. However, boys
      who attended private schools were more likely to gain prestige through being the
      class clown. Taken together, the findings show few differences between avenues to
      prestige for girls in private and public high schools, and differences for boys
      that are not uniformly in the direction that parents and private school advocates
      would predict or desire.

PMID- 15563036
TI  - Gender, grade, and relationship differences in emotional closeness within
      adolescent friendships.
AB  - Previous research has examined gender and grade differences in the emotional
      closeness of adolescents' same- and cross-sex friendships. However, findings from
      these studies have been inconsistent because they have failed to (1)
      differentiate between cross-sex friendships and romantic relationships and (2)
      compare same- and cross-sex friendships. In an attempt to clarify previous
      findings, gender and grade differences in adolescent reports of emotional
      closeness within same- and cross-sex friendships were examined in the current
      study. Responses from two hundred seventy adolescents indicated gender
      differences in reports of time spent with their friends daily and levels of
      relationship closeness, cohesion, and commitment. Further, grade moderated
      relationship differences in reports of relationship cohesion and closeness.
      Differences in predictors of intimacy support previous studies that have found
      grade and gender differences in levels of intimacy in adolescents' same- and
      cross-sex friendships. Results also elaborate on previous research by indicating
      grade differences in adolescents' perceptions of cohesion and closeness in their
      same- and cross-sex friendships. Findings are discussed in terms of understanding
      differences in adolescent reports of intimacy within same- and cross-sex
      friendships.

PMID- 15563037
TI  - Positive psychology and adolescent mental health: false promise or true
      breakthrough?
AB  - The emerging field of positive psychology has pledged to improve the mental
      health of American adolescents. Yet, without a principle-based conceptual
      foundation to guide its study of optimal youth functioning, positive psychology
      will ultimately fail to keep its promise. This paper suggests that the principles
      of Mind, Thought and Consciousness can provide positive psychology with a clearer
      understanding of optimal psychological functioning, serve as a unifying
      conceptual framework to guide its proposed mission, and lead to a true
      breakthrough in adolescent mental health. It first describes how the logic of
      these principles accounts for all subjective human experience. It then
      demonstrates how optimal mental health is generated, and how it can be maintained
      irrespective of present or past circumstances. Finally, it discusses how several
      contemporary models of positive psychology (i.e., Csikszentmihalyi's flow.
      Seligman's learned optimism, Goleman's emotional intelligence, and Buss's
      evolutionary perspective) can be simplified and clarified using the logic of the
      above three principles.

PMID- 15563038
TI  - The wish to die and the wish to commit suicide in the adolescent: two different
      matters?
AB  - We shall try to demonstrate the difference between two wishes--the wish to die
      and the wish to commit suicide--as they express themselves during adolescence.
      First, death is seen as irreversible, while the suicidal act, at least during
      adolescence, is seen as reversible. While thoughts of suicide may be a part of
      normal adolescence, and the suicidal act a manifestation of pathological
      development specific to this stage in life, the wish to die has no age
      restrictions and may accompany life as a shadow, devoid of any suicidal act, for
      many years. It should be noted that both of these wishes may be balanced with the
      wish to live. Pathology appears when there is an imbalance of wishes and abnormal
      developmental processes. This imbalance can result in two distinct activities:
      suicidal acts and death behaviors. We suggest that the two stem from different
      mechanisms and personality pathologies. Therefore, they should be evaluated
      separately in order to better understand differences between suicidal and other
      aggressive acts and manifestations of the death wish during adolescence.

PMID- 15563039
TI  - Adolescent suicide risk: four psychosocial factors.
AB  - Suicide is a leading cause of death among adolescents. This study examined the
      suicidal ideation, behavior, and attempt history of 100 adolescents ages
      seventeen to nineteen. Four psychosocial factors were found to be important for
      overall suicide risk: hopelessness, hostility, negative self-concept, and
      isolation. It is suggested that focusing on these four psychosocial factors would
      enhance suicide assessment and prevention efforts with adolescents.

PMID- 15563040
TI  - Adolescent and parent perceptions of media influence on adolescent sexuality.
AB  - Empirical evidence suggests that television and other media influence
      adolescents' attitudes and behaviors. Much of the research in this area is based
      on surveys in which adolescents are asked to rank the relative importance of a
      fixed set of factors such as parents, peers, and media. We reviewed data from
      focus groups conducted with adolescents and their parents to examine the extent
      to which adolescents identify--without prompting--media as a source of influence
      on sexual behavior. Adolescents seemed indifferent to media influence (e.g.,
      media influence was mentioned in only one adolescent focus group), but their
      parents expressed significant concern about media influence. Future research
      should investigate the extent to which influences exist outside of adolescents'
      consciousness. For now, parents and sexuality educators may need to convince
      adolescents that concerns about the media are valid before trying to change media
      influenced behavior.

PMID- 15563041
TI  - Social network predictors of bullying and victimization.
AB  - This study examined whether bullies, victims, and aggressive victims (those who
      are both bullies and victims) differed on classroom social network variables,
      gender, and ethnicity. Survey data were collected from a primarily Latino and
      Asian sample of 1,368 Southern California 6th graders (mean age = 11.3 years).
      Logistic regression analyses were performed to determine whether network
      characteristics and ethnicity were associated with each of the outcome variables.
      Consistent with social cognitive theory, friends' participation in aggressive
      behaviors was positively associated with being a bully or an aggressive victim,
      and negatively associated with being a victim. Consistent with social dominance
      theory, the number of friendship nominations received was negatively associated
      with being a victim. Female bullies received fewer friendship nominations, but
      had a higher proportion of reciprocated friendships. Victims were
      disproportionately Asian. The findings suggest that bullying prevention efforts
      targeting highly aggressive students may also diffuse to their friends, and that
      assertiveness training in handling aggressive situations may successfully combat
      bullying and aggression.

PMID- 15563042
TI  - A teenager revisits her father's death during childhood: a study in resilience
      and healthy mourning.
AB  - "Debbie," 14, was 8 when her father died. During 4 interviews over 3 months,
      Debbie described the impact of his death as she progressed from childhood to
      adolescence. Themes drawn from her experience were related to theories of
      development, bereavement, and resilience. Triangulating interviews with her
      mother and brother established validity. Results indicated that Debbie
      experienced healthy mourning--without depression or other debilitating effects-
      due to supportive people in her family, her strong self-concept, and her capacity
      to think through her experiences positively. Evidence of protective factors,
      notably Debbie's relationship with her mother, contributed to her resilience. The
      author concludes that childhood bereavement studies and resilience research can
      be mutually informative and that dialogue between their practitioners should
      increase.

PMID- 15563043
TI  - Effects of parent education on knowledge and attitudes.
AB  - This study evaluated 42 pregnant and parenting adolescents (aged 13 to 20 years)
      and adults (who began parenting as adolescents) enrolled in parenting classes.
      The Parent as a Teacher Inventory and the Adult-Adolescent Parenting Inventory
      were used to measure change in knowledge and attitudes following participation in
      the classes. The findings indicated significant improvement as a result of parent
      education.

PMID- 15563044
TI  - Untreated recovery from eating disorders.
AB  - This retrospective study explored the experience of recovery from anorexia
      nervosa and bulimia nervosa without professional treatment. A nine-question open
      ended electronic survey was posted for a period of four months at a mid-western
      university. Sixteen female and two male respondents reported recovery from
      adolescent-onset full syndrome anorexia nervosa or bulimia nervosa. All
      respondents reported onset factors supporting a sociocultural etiology. Recovery
      was initiated through the empathic, participatory efforts of parents and friends,
      or was self-initiated. Respondents with the shortest disorder duration and most
      complete recovery reported early parental intervention. Onset factors similar to
      those in research with a clinically treated population were found. Implications
      of the findings are discussed.

PMID- 15563045
TI  - Walk and Talk: an intervention for behaviorally challenged youths.
AB  - This qualitative research explored the question: Do preadolescent and adolescent
      youths with behavioral challenges benefit from a multimodal intervention of
      walking outdoors while engaging in counseling? The objective of the Walk and Talk
      intervention is to help the youth feel better, explore alternative behavioral
      choices, and learn new coping strategies and life skills by engaging in a
      counseling process that includes the benefits of mild aerobic exercise, and that
      nurtures a connection to the outdoors. The intervention utilizes a strong
      therapeutic alliance based on the Rogerian technique of unconditional positive
      regard, which is grounded and guided by the principles of attachment theory. For
      eight weeks, eight students (aged 9 to 13 years) from a middle school in Alberta,
      Canada, participated weekly in the Walk and Talk intervention. Students' self
      reports indicated that they benefited from the intervention. Research
      triangulation with involved adults supported findings that indicated the students
      were making prosocial choices in behavior, and were experiencing more feelings of
      self-efficacy and well-being. Limitations, new research directions, and
      subsequent longitudinal research possibilities are discussed.

PMID- 15563046
TI  - Adolescents' perception of the ideal mate: its relationship to parental
      characteristics in intact and nonintact families.
AB  - The relation of adolescents' experiencing parental divorce, their perception of
      parents' characteristics, and their perception of the ideal mate's
      characteristics was investigated. One hundred adolescents from intact families
      and 79 from nonintact families were asked to rank both the degree to which each
      of 40 personality traits characterized their parents and the degree to which each
      characterized an ideal partner. The results indicated that there was no
      significant difference between adolescents from intact and nonintact families in
      the independence of their characterizations of their ideal mate and of their
      parents. However, differences were found on some of the personality dimensions
      that were investigated. These and other findings are discussed within the
      framework of psychoanalytic theory.

PMID- 15563047
TI  - Management of localised prostate cancer.
AB  - Prostate cancer is the commonest cancer in men, with over 27,000 new cases
      diagnosed each year in the UK. Here we review the management of men with the
      early (localised) form of the disease.

PMID- 15563048
TI  - Probiotics for gastrointestinal disorders.
AB  - In recent years, interest has increased in the use of probiotics (orally
      administered micro-organisms) to treat people with a wide range of health
      problems. In the UK, probiotic preparations are classified as foods or food
      supplements so, unlike for medicines, there are no regulations to prevent their
      manufacturers from making non-specific promotional health claims, such as "Gives
      your patients a boost". Here we focus on the use of probiotics to treat people
      with gastrointestinal disorders. In a future issue, we will consider their use in
      atopic disease.

PMID- 15563049
TI  - Depression, anxiety, anger, and somatic symptoms in patients with body dysmorphic
      disorder.
AB  - Body dysmorphic disorder (BDD) is a relatively common and impairing disorder.
      However, little is known about non-BDD symptoms and well-being in patients with
      this disorder. Seventy-five outpatients with DSM-IV BDD completed the Symptom
      Questionnaire, a validated self-report measure with four scales: depression,
      anxiety, somatic/somatization, and anger-hostility. Scores were compared to
      published norms for normal subjects and psychiatric outpatients. Participants in
      an open-label fluvoxamine trial completed the Symptom Questionnaire at baseline
      and endpoint. Compared to normal controls, BDD subjects had markedly elevated
      scores on all four scales, indicating severe distress and psychopathology.
      Compared to psychiatric patients, BDD subjects had higher scores on the
      depression, anxiety, and anger/hostility scales but not on the
      somatic/somatization scale. Scores on all scales significantly decreased with
      fluvoxamine. In conclusion, patients with BDD have markedly high levels of
      distress, are highly symptomatic, and have poor well-being in the domains of
      depression, anxiety, somatic symptoms, and anger-hostility. All of these symptoms
      significantly improved with fluvoxamine.

PMID- 15563050
TI  - Enhancing patient satisfaction and increasing treatment compliance: patient
      education as a fundamental component of PTSD treatment.
AB  - Posttraumatic Stress Disorder (PTSD) is the modal mental health problem
      afflicting combat veterans. In addition to the significant distress resulting
      from the disorder itself, PTSD has been associated with significant medical
      comorbidity and increased utilization of medical services. Interventions have
      historically focused on targeting symptoms directly, with comparatively little
      attention to systematically educating patients about the etiology and maintenance
      of the disorder and associated features and treatment issues. This descriptive
      study summarizes an eight-week PTSD patient education and orientation group.
      Seventeen patients admitted consecutively to the PTSD Clinic at a large VA
      hospital completed surveys of patient satisfaction with services and motivation
      to comply with treatment regimens upon completion of the group. Participants
      reported very high satisfaction with services, increased awareness of PTSD
      treatment options, greater optimism and symptom improvement and enhanced
      motivation to continue with treatment as a result of attending the group.

PMID- 15563051
TI  - Service utilization among compensation-seeking veterans.
AB  - To examine the relationship between compensation-seeking status, symptom
      reporting, and health care utilization among combat veterans presenting for a
      Posttraumatic Stress disorder (PTSD) evaluation. Archival data for 68 veterans
      was drawn from electronic medical records for which compensation-seeking status
      was available. Consistent with previous findings, self-reports of distress and
      validity scale indices on the Minnesota Multiphasic Personality Inventory-2 (MMPI
      2) were higher among compensation-seeking (CS) veterans than noncompensation
      seeking (NCS) veterans despite a lack of difference in actual PTSD diagnoses.
      However, no significant differences emerged between these two groups on
      healthcare utilization indices. Although exploratory analyses did not yield
      significant group differences on various healthcare indices, there was a trend
      for CS veterans to use PTSD services more, suggesting the need to further explore
      utilization patterns among these groups.

PMID- 15563052
TI  - Prior history of physical and sexual abuse among the psychiatric inpatient
      population: a comparison of males and females.
AB  - Despite increasing attention given to the high prevalence and effects of abuse in
      the severely mentally ill, few studies have looked at its effects among males.
      While both male and female psychiatric patients report greater abuse history than
      the general population, studies have focused on females alone. The current study
      compared the effects of abuse history between 271 severely mentally ill males (n
      = 160) and females (n = 111). The mean age of participants was 33.7 years (SD =
      9.73), and included 129 Caucasians, 120 African Americans, 15 Hispanic-Americans,
      and 7 "Other" (i.e., Asian and native American descent). Primary Axis I diagnoses
      included Bipolar disorder (23.2%) major depressive disorder (27.7%) schizophrenic
      disorder (26.6%), substance-related disorders (10.3%), and miscellaneous
      disorders (12.1%). Each patient completed a comprehensive assessment, including
      clinician ratings, self-report measures, clinical and structured interviews.
      Comparisons between genders revealed that females were more likely to report both
      physical and sexual abuse, and males were more likely to report no history of
      abuse. In addition, Caucasians were more likely to report abuse than were African
      Americans, and voluntary patients were more likely to endorse abuse history than
      those admitted involuntarily. Few gender differences were found in psychological
      symptoms among males and females. Satisfaction with the home environment was
      significantly lower for abused than nonabused females. This was not true for
      males. However, abused psychiatric patients were perceived by the physicians,
      nurses, and themselves as having greater emotional disturbance than were
      nonabused patients, regardless of gender. Clinical implications are discussed.

PMID- 15563053
TI  - Case identification of mood disorders in Asian American and Caucasian American
      college students.
AB  - Past studies have sometimes found that Asian American participants score higher
      on checklists that measure psychological distress compared to Caucasian American
      participants. However, studies using diagnostic interviews have not found
      corresponding elevated rates of mood disorders in Asian American participants. In
      the present study, Asian American (n = 238) and Caucasian American students (n =
      556) completed checklist measures of distress (the Beck Depression Inventory, BDI
      and the Mood and Behavior Questionnaire, MBQ) and a subsample of students (n =
      118) received a diagnostic interview. Asian American students had higher BDI
      scores, but the groups did not differ on either the MBQ, a measure closely tied
      to DSM criteria for major depression, or on rates of current mood disorders.
      Elevated BDI scores overestimate rates of mood disorders, particularly in Asian
      American students.

PMID- 15563054
TI  - Changes in satisfaction with mental health services among blacks, whites, and
      Hispanics in the Department of Veterans Affairs.
AB  - This paper presents an analysis of changes in satisfaction of minorities with
      inpatient mental health services provided by the Veterans Health Administration
      (VHA) during a period of major system change (1995-2001). Post discharge data
      from 16,223 veterans who received inpatient VHA mental healthservices at 87
      medical centers during this period was examined using hierarchical linear models.
      Blacks were found to have higher satisfaction levels on most measures over the
      period of study while the satisfaction of whites and Hispanics were not
      significantly different. There was little change over the study period in the
      relative satisfaction of minorities and whites. Changes in patterns of VHA mental
      health care have not adversely affected the satisfaction of minority veterans.

PMID- 15563055
TI  - [Mechanisms of sodium ferulate inhibition of collagen synthesis in hepatic
      stellate cells].
AB  - AIM: To study the mechanisms of sodium ferulate (SF) on inhibition of collagen
      synthesis in hepatic stellate cells. METHODS: Collagen synthesis was analyzed by
      measuring 3H-proline incorporation. ELISA method was used to study the effect of
      SF on transforming growth factor beta1 (TGFbeta1) level in cultured HSC-T6 cell.
      The effect of SFon the TGFbeta1 activity in the supernatant of culture was
      analyzed by mink lung epithelial cell (Mv1Lu) proliferation inhibition by MTT
      assay. RESULTS: SF inhibited collagen synthesis in hepatic stellate cells
      stimulated with TGFbeta1. SF was shown to decrease TGFbeta1 level in the
      supernatant of HSC-T6 increased by oxidative stress. TGFbeta1 activity was
      intervened by SF. CONCLUSION: SF could decrease collagen synthesis, with
      mechanism may be associated with that SF intervened TGFbeta1 activity, and
      reduced the level of TGFbeta1 increased by oxidative stress.

PMID- 15563056
TI  - [Gender-related differences in metabolism of the enantiomers of trans tramadol
      and trans O-demethyltramadol in rat liver microsomes].
AB  - AIM: To investigate the gender-related differences in the metabolism of trans
      tramadol (trans T) enantiomers and the glucuronidation of trans O
      demethyltramadol (M1) enantiomers. METHODS: In vitro, trans T or M1 were
      separately incubated with liver microsomes of male or female rats. The
      concentrations of the enantiomers of trans T and M1 were determined by an HPCE
      method. RESULTS: Compared with (+)-enantiomers, (-)-trans T was preferentially
      metabolized, and (-)-M1 was produced faster in rat liver microsomes. (+)-M1 and (
      )-M1 were preferentially glucuronidated in the liver microsomes of male and
      female rats, respectively. Compared with those in male rat liver microsomes, the
      enantiomeric ratios of CLint for M1 formation and M1 glucuronidation were more
      deviated from 1 in female rat liver microsomes. CONCLUSION: In vitro, trans T
      metabolism, M1 formation and M1 glucuronidation were found to be stereoselective
      in rat liver microsomes. There were gender-related differences in the
      stereoselectivity in M1 formation and M1 glucuronidation, with a larger extent in
      female rat liver microsomes.

PMID- 15563057
TI  - [Effects of two metabolites of cultured marine fungus, Halorosellinia oceanicum
      323, on the contraction of isolated guinea-pig ileum].
AB  - AIM: To investigate the effects of 323-A and 323-B, two isomers extracted from
      the metabolites of cultured marine fungus, Halorosellinia oceanicum 323, on the
      contraction of isolated guinea pig ileum (GPI). METHODS: The GPI contractions
      were recorded with a two-channel-physiological recorder with tension transducers.
      Cumulative dose-response curves of contractions of isolated GPI induced by
      histamine (Hist), acetylcholine (ACh) and potassium chloride (KCl) were
      constructed, then the influences of 323-A and 323-B on each curve were observed.
      Furthermore, possible mechanisms underlying effects of the two compounds were
      explored by analyzing their influences on the biphasic contractile response to
      ACh, with comparison of a calcium antagonist, verapamil (Ver). RESULTS: The data
      indicated that both 323-A and 323-B inhibited the contractile actions of GPI
      triggered by Hist, ACh and KCl in a concentration-dependent manner, with pD2'
      values of 5.13, 4.97, 5.36 and 5.51, 5.56, 5.62, respectively. The initial phase
      component of the ACh-elicited contractions, in the absence of external Ca2+, was
      significantly reduced by 323-A, 323-B, as well as Ver, whereas the subsequent
      sustained tonic contractions induced by adding Ca2+ to the bath solution were
      almost unaffected. CONCLUSION: These results suggest that 323-A and 323-B have
      calcium antagonistic effects similar to that of Ver in mechanisms, and they might
      have potential to be developed as calcium antagonists.

PMID- 15563058
TI  - [Synthesis and antitumor activity of 20-O-linked camptothecin ester derivatives].
AB  - AIM: To improve the profile of 20 (S)-camptothecin, a series of 20-O-linked
      camptothecin phenoxyacetic acid ester derivatives have been designed. METHODS:
      These derivatives were synthesized by the method of acylation. Their chemical
      structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the
      compounds were tested by MTT assay. The in vivo antitumor activities of these
      esters were evaluated against mouse liver tumor H22 in mice. RESULTS: Twelve
      derivatives of camptothecin ester are new compounds. CONCLUSION: In vitro and in
      vivo antitumor activity has indicated that some derivatives appeared
      significantly more effective than topotecan in the H22 mouse liver tumoral model.

PMID- 15563059
TI  - [Studies on the alkaloids from Salsola collina Pall].
AB  - AIM: To study the chemical constituents of Salsola collina Pall.. METHODS:
      Compounds were isolated by silica gel column chromatography. IR, MS, 1HNMR,
      13CNMR, HMQC, HMBC, DEPT were used for the structural identification. RESULTS:
      Two amide alkaloids were obtained. They were identified as N-transferuloyl-3
      methyldopamine (I), (10bS)-1,2,3,5,6, 10b-hexahydropyrrolo [2,1-a]-8,9
      dihydroxyisoquinoline-3-one (II). CONCLUSION: Compound I was isolated from this
      genus for the first time. Compound II is a new compound named salsoline A.

PMID- 15563060
TI  - [Structure identification of jujuboside D].
AB  - AIM: To study the chemical constituents of Ziziphus jujuba Mill var. Spinosa
      (Bunge) Hu ex. H. F. Chou. METHODS: To separate the constituents by using various
      kinds of chromatography and identify their structures on the basis of spectral
      analysis. RESULTS: Five compounds were isolated and their structures were
      established as jujuboside D (1), jujuboside A (2), 5,7,4'-trihydroxyflavonol-3-O
      beta-D-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3), 6'''-coumaroylspinosin
      (4) and phenylalanine (5). CONCLUSION: Compound 1 is a new compound named
      jujuboside D, 4 is reported as rotamer for the first time, 3 and 5 isolated from
      this plant for the first time.

PMID- 15563061
TI  - [Studies on the chemical constituents of Evodia rutaecarpa (Juss.) Benth].
AB  - AIM: To study the chemical constituents of Evodia rutaecarpa (Juss.) Benth.
      METHODS: The crude total alkaloids were enriched by acid-base treatment and
      solvent extraction. Isolation and purification were carried out by silica gel
      column chromatography and recrystallization etc. Structural determination of the
      pure compounds were based on physico-chemical properties and various spectral
      data analysis (1HNMR, 13CNMR, UV, IR, 1H-1H COSY, HMQC, HMBC, ESIMS, HREIMS,
      NOESY). RESULTS: Fourteen compounds were obtained from Evodia rutaecarpa, ten of
      them were identified as evodianinine (1), rutaecarpine (2), evodiamine (3),
      wuchuyuamide I (4), hydroxyevodiamine (5), limonin (6), daucosterol (7),
      triacontanoic acid (8), nonacosane (9) and beta-sitosterol (10). CONCLUSION:
      Compound 1 is a new alkaloid named evodianinine.

PMID- 15563062
TI  - [Pharmacokinetics of m-nifedipine in Beagle dogs].
AB  - AIM: To study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.
      METHODS: The Beagle dogs were divided into two groups. m-Nif was intravenously
      administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and
      it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of
      1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected
      by reversed phase high performance liquid chromatography. The pharmacokinetic
      parameters were calculated by 3P97 software. RESULTS: When m-Nif was
      intravenously administered, the plasma concentration-time curve was fit to a two
      compartment model and T1/2beta was 117 min. When m-Nif was orally administered,
      the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke)
      and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(
      1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of
      3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the
      high dose of 10.37 mg x kg(-1), respectively. CONCLUSION: It was showed that the
      speed of elimination of m-Nif was high in Beagle dogs. The absolute
      bioavailability of m-Nif given orally was very low.

PMID- 15563063
TI  - [Determination of progesterone and its main metabolite in rat plasma and uterus
      using HPLC].
AB  - AIM: To quantify progesterone (P) and one of its metabolites 20alpha-hydroxy-4
      pregnen-3-one (20alpha-OHP) in rat plasma and uterus after im administration of
      progesterone. METHODS: Plasma and uterus samples were prepared by liquid-liquid
      extraction and separated through Shimadzu VP-ODS column (150 mm x 4.6 mm ID, 5
      microm). The mobile phase consisted of acetonitrile and water (60: 40, adjusted
      to pH 4.0 with phosphoric acid). The detector was set at 240 nm. Norgestrel was
      used as the internal standard. RESULTS: Cmax of P in plasma was (508 +/- 62)
      microg x L(-1), Tmax was (3.2 +/- 0.4) h, T1/2 (ke) was (10 +/- 4) h and mean
      AUC0-48h was (5886 +/- 1573) microg x L(-1) x h. The maximum concentration of P
      in uterus was (1.7 +/- 1.1) microg x g(-1) and the peak time was (5.2 +/- 1.11)
      h. 20alpha-OHP showed a similar Tmax with P. CONCLUSION: The method is accurate
      and convenient. It can be used to determine P and its main metabolite 20alpha-OHP
      simultaneously for studying their preclinical pharmacokinetics.

PMID- 15563064
TI  - [Determination of five components in compound hypotensive tablet by HPLC].
AB  - AIM: To establish a method for the determination of the five components
      (reserpine, chlordiazepoxide, hydrochlorothiazide, dihydralazine sulfate,
      triamterene) in compound hypotensive tablet. METHODS: The chromatography was
      performed using a CN column with acetontrile-0.1 mol L(-1) sodium heptasulfonate
      solution (7:3) and (5:5) as the mobile phases. The detection wavelength was 267
      nm for reserpine, chlordiazepoxide and hydrochlorothiazide, 310 nm for
      dihydralazine sulfate, 360 nm for triamterene. RESULTS: The linear range of each
      component was tested, and the recovery and stability of each component was
      satisfactory, three lots of samples were determined using the method. CONCLUSION:
      This is an accurate and credible quality control method for compound hypotensive
      tablet.

PMID- 15563065
TI  - [Study on fingerprint of rhizoma chuanxiong by HPLC-DAD-MS].
AB  - AIM: To establish a high performance liquid chromatographic fingerprint for the
      quality control of rhizoma Chuanxiong, a traditional Chinese medicine derived
      from the root of Ligusticum chuanxiong Hort.. METHODS: An on-line optimized HPLC
      DAD-MS technique was employed. The HPLC analysis was performed on a Waters
      Symmetry C18 column (150 mm x4. 6 mm ID, 5 microm) with a Waters Spherisorb S5
      ODS2 (10 mm x 4.6 mm) guard column. The mobile phase consisted of A (methanol)
      and B (0.25% acetic acid). Components were separated using the following gradient
      profile: 32% B at 0-3 min, 32%-85% B at 3-33 min, 85%-100% B at 33-52 min; flow
      rate was 0.7 mL x min(-1). DAD was set from 190 to 400 nm, the fingerprint was
      monitored at 294 nm. All mass spectra were acquired in the positive ion mode with
      electrospray ionization; the full scan mass spectrum was recorded over the range
      of m/z 100-800. Nine samples from three companies were analyzed; the main
      characteristic peaks were identified based on the comparison of UV and MS spectra
      of each analyte with that of authentic compounds and literature data. RESULTS:
      The HPLC fingerprint was established based on the analysis of nine rhizoma
      Chuanxiong herbal samples supplied by three companies. Twenty-one characteristic
      peaks were found in all nine samples. These peaks were classified into four
      groups: group I at 0-12 min, three peaks were found, and the marker peak 3 was
      confirmed as ferulic acid; group II at 12-24 min, four peaks were found, and the
      marker peaks 4 and 5 were identified as senkyunolide I and senkyunolide H; group
      III at 24-32 min, there were seven peaks, and the marker peaks 9, 11, 13 and 14
      were elucidated as senkyunolide A, coniferylferulate, ligustilide and 3
      butylidenephthalide, respectively; group IV at 32-50 min, seven peaks were
      observed, and the marker peaks 15 and 17 were identified as riligustilide and
      levistolide A. The peak areas of 13 main peaks with normalized peak area (1% were
      determined. Using the most abundant peak 13 as the reference peak, the calculated
      relative retention times (tR of the characteristic peak/tR of the reference peak)
      among nine samples were consistent (RSD < or = 1%), while the calculated relative
      peak areas (peak area of the characteristic peak/peak area of the reference peak)
      among nine samples were significantly different (P < 0.001), indicating that all
      nine samples tested contain similar 13 main components with different quantities.
      CONCLUSION: The established HPLC fingerprint is very specific, and can be used to
      evaluate the quality consistency of different rhizoma Chuanxiong herbs.

PMID- 15563066
TI  - [Application of PSD-MALDI-TOF-MS to protein identification].
AB  - AIM: To identify protein spots on two dimentional protein electrophoresis (2DE)
      by post-source decay (PSD) technique associated with library search. METHODS: The
      PSD-MALDI-TOF-MS method was set up by a segment of ACTH and a peptide digested by
      trypsin for TPA. RESULTS: Two unknown protein spots on 2DE were identified as 40S
      ribosomal protein S12 and dnaK suppressor protein separately by established PSD
      MALDI-TOF-MS method. CONCLUSION: PSD technique has greater application prospects
      in peoteomics.

PMID- 15563067
TI  - [The absorption kinetics of silymarin microemulsion in rat intestine].
AB  - AIM: To survey the morphology and size distribution of silymarin microemulsion,
      to investigate the absorption of silymarin microemulsion in rat intestine
      compared with the absorption of silymarin micelle in rat Jejunum. METHODS: The
      intestine in rats was canulated for in situ recirculation. RESULTS: The
      absorption rate constants (Ka) of silymarin microemulsion at the entire
      intestine, ileum jejunum, duodenum and colon were 6.22 x 10(-2), 2.27 x 10(-2),
      1.9 x 10(-2), 1.9 x 10(-2), 1.05 x 10(-2) and 0.43 x 10(-2) h(-1), respectively.
      The absorption rate constants of two kinds of silymarin micelle at jejunum were
      0.36 x 10(-2), 0.65 x 10(-2) h(-1). CONCLUSION: Silymarin microemulsion was well
      absorbed at the middle and lower segments of intestine in rats. The absorption
      was a first-order process with the passive diffusion mechanism.

PMID- 15563068
TI  - [Study on cytomedicine of alginate-poly(L) lysine-alginate microencapsulated
      hybridoma cells].
AB  - AIM: To study the cytomedicine of alginate-poly (L) lysine-alginate (APA)
      microencapsulated hybridoma cells and their characteristics. METHODS: The spleen
      cells taken from BALB/C mice immunized with purified human IgG1 kappa type were
      fused with mouse myeloma cells SP2/0. The hybridoma cell lines secreting
      monoclonal antibodies (mAb) against human IgG1 kappa type was named JY-A1. The
      APA microencapsulated JY-A1 cells were prepared with a high-voltage electrostatic
      system. Microencapsulation parameters were optimized and their morphology was
      studied. The mechanical strength and chemical intensity of microcapsules were
      measured. The mAb secrete from APA microencapsulated JY-A1 cells was determined
      by ELISA kit. The microcapsules injected into mice abdominal cavity previously
      were recovered at intervals. RESULTS: The microcapsules prepared in the same
      condition of the high-voltage electrostatic system were round and homogeneous.
      The mAb secreted by the microencapsulated JY-A1 cells were shown to permeate the
      membranes of APA microcapsules in vitro. After an intraperitoneal injection to
      mice, APA microcapsules were recovered on day 7, 14, 28, 56. The electron
      microscopy study revealed that the majority of recovered microcapsules were
      intact, and no evidence of immunological reaction in terms of fibrosis.
      CONCLUSION: APA microencapsulated hybridoma cells prepared by high-voltage
      electrostatic system have good mechanical strength and chemical intensity. The
      APA microencapsulated hybridoma cells can maintain physiological functions in
      vitro, and the microcapsules have good biocompatibility in vivo.

PMID- 15563069
TI  - [Preparation and evaluation in vivo and in vitro of glimepiride gel-matrix
      controlled-release patch].
AB  - AIM: To study the pharmaceutical characterization, the pharmacokinetics and
      relative bioavailability of glimepiride gel-matrix controlled-release patch in
      rats. METHODS: An HPLC method was established for the determination of
      glimepiride in the permeation receptor and patch. The permeation rate and
      penetration mechanism of glimepiride-TDDS through rabbit skin in vitro was
      examined. The determination of drug content and the examination of weight
      difference and stability of the glimepiride-TDDS were carried out. Another HPLC
      method after pre-column derivatization was developed to determine the glimepiride
      serum concentration and then employed to study the pharmacokinetics and relative
      bioavailability of glimepiride after a single dose of oral or patch
      administration in rats. RESULTS: The permeation tests through excised rabbit skin
      demonstrated that the optimized glimepiride controlled-release patch exhibited
      zero-order kinetic characteristics that satisfied the demands of original design.
      The determination of glimepiride content and the quality control of weight
      difference of the patch accorded with Pharmacopoeia of the People's Republic of
      China of 2000 edition and the pharmaceutical characterization showed good
      stability. The HPLC method for the determination of serum glimepiride was shown
      to be a sensitive and simple one. The pharmacokinetic results showed that TDDS
      could decrease the maximum serum concentration, prolong the peak time, extend the
      MRT by 5.5 times compared with oral administration and maintain the serum
      concentration of glimepiride at a higher level even after 120 h of
      administration. The relative bioavailability of glimepiride-TDDS was 20.3% versus
      oral administration. CONCLUSION: The glimepiride-TDDS showed a slower, longer and
      smoother serum concentration-time profile, as compared with conventional oral
      administration in both absorption and elimination phase. As a result, it was
      evident that the patch exhibited good controlled-release properties.

PMID- 15563070
TI  - Influence of light and temperature on the stability of procaine hydrochloride
      injection.
AB  - AIM: To study the influence of light and heat on the stability of procaine
      hydrochloride injection. METHODS: Accelerated tests upon exposure to light at
      high temperatures were employed. RESULTS: In experiments with either isothermal
      heating or exposure to light at high temperatures, the drug degradation rate
      obeys first-order kinetics. The total rate constant, ktotal, caused by both light
      and heat can be divided into two parts: ktotal = kdark + klight, where kdark and
      klight are the rate constants caused by heat and light, respectively. The klight
      can be expressed as klight = Alight x E x exp(-Ea,light/RT). Where E is the
      illuminance of light, Alight is an experimental constant related to light
      sources, and Ea,light is an experimental constant. CONCLUSION: Because the form
      of klight is similar to the Arrhenius equation, it is suggested that Ea,light
      might be the observed activation energy of the rate-determining step of the
      subsequent processes of the photochemical reaction. This viewpoint is supported
      by the fact that the Ea,light is independent of light sources.

PMID- 15563071
TI  - [Studies on the liver targeting of norcantharindin microemulsion].
AB  - AIM: To study the morphology, particle size distribution and biological
      reliability of the norcantharindin (NCTD)-loaded microemulsion and
      pharmacokinetics of the W/O norcantharidin-loaded microemulsion in mice. METHODS:
      The concentration of NCTD in plasma and tissues were determined by GC method. The
      data obtained were processed using 3P87 program. RESULTS: The mean particle
      diameter of microemulsion was (44 +/- 9) nm. The concentration-time curve of NCTD
      loaded microemulsion and NCTD injection was fitted to a two-compartment model. At
      the same dosage, the pharmacokinetic study for NCTD-loaded microemulsion showed
      the NCTD microemulsion had relatively longer circulating time in mice. Area under
      the curve of concentration versus time (AUC), mean residence time (MRT) and half
      life (T1/2) for microemulsion and injection were (29.7 +/- 0.9) mg x h x L(-1),
      (9.25 +/- 0.09) mg x h x L(-1), (110 +/- 11) h, (86.7 +/- 0.8) h, (103 +/- 12) h,
      (42 +/- 4) h, respectively. Targeting index of NCTD microemulsion in liver and
      kidney in mice were 0.43 and 0.12 after iv NCTD-loaded microemulsion. The effects
      of biological reliability was not significantly different between NCTD
      microemulsion and NCTD injection in vivo and in vitro. CONCLUSION: The liver
      targeting absorptive capability of NCTD-loaded microemulsion was enhanced and the
      release time was extended compared with NCTD injection. While the microemulsion
      vehicles could decrease the kidney distribution of NCTD.

PMID- 15563072
TI  - [Effects of Ginkgo biloba extract on number and activity of endothelial
      progenitor cells from peripheral blood].
AB  - AIM: To investigate whether Ginkgo biloba extract can augment endothelial
      progenitor cell (EPC) number, and promote EPC proliferation, migration and
      adhesion. METHODS: Total mononuclear cells (MNCs) were isolated from peripheral
      blood by Ficoll density gradient centrifugation, and then the cells were plated
      on fibronectin-coated culture dishes. After 7 days of culture, attached cells
      were stimulated with Ginkgo biloba extract (10, 25 and 50 mg x L(-1)) or vehicle
      control for the respective time points (6, 12, 24 and 48 h). EPC were
      characterized as adherent cells double positive for DiLDL-uptake and lectin
      binding by direct fluorescent staining under a laser scanning confocal
      microscope. EPC were further documented by demonstrating the expression of CD34,
      VEGFR-2 and AC133 with flow cytometry. EPC proliferation, migration and in vitro
      vasculogenesis activity were assayed with MTT assay, modified Boyden chamber
      assay and in vitro vasculogenesis kit, respectively. EPCs adhesion assay was
      performed by replating MNCs on fibronectin-coated dishes, and then counting
      adherent cells. RESULTS: Incubation of isolated human MNCs with Ginkgo biloba
      extract increased the number of EPC, maximum at 25 mg x L(-1), 24 hours
      (approximately 1-fold increase, P < 0.01). In addition, Ginkgo biloba extract
      promotes EPC proliferative, migratory, adhesive and in vitro vasculogenesis
      capacity. CONCLUSION: Ginkgo biloba may promote EPC augmentation and enhance its
      functional activity.

PMID- 15563073
TI  - [Protective effects of phenolic alkaloids from Menispermum dauricum on
      inflammatory injury following focal cerebral ischemia-reperfusion in rats].
AB  - AIM: To study the protective effects of phenolic alkaloids from Menispermum
      dauricum (PAMd) on inflammatory injury following focal cerebral ischemia
      reperfusion in rats. METHODS: The right middle cerebral artery of the rat was
      occluded by inserting a nylon suture through the internal carotid artery for 2 h,
      followed by reperfusion by withdrawing the suture. The expression of
      intercellular adhesion molecule-1 (ICAM-1) was observed by immunohistochemistry
      staining. The adhesiveness and infiltration of leucocytes were observed by HE
      staining. The activity of myeloperoxidase (MPO) and the content of nitric oxide
      (NO) in the cortex and hippocampus were measured. RESULTS: PAMd was shown to
      markedly inhibit ICAM-1 expression, alleviate the adhesiveness and infiltration
      of leucocytes, and decrease the MPO activity and the NO content in ischemic
      cortex and hippocampus. CONCLUSION: PAMd has protective effects on inflammatory
      injury following focal cerebral ischemia-reperfusion by inhibiting ICAM-1
      expression, alleviating the adhesiveness and infiltration of leucocytes and
      decreasing the generation of NO.

PMID- 15563075
TI  - [Several surgical therapeutical problems of the thyroid carcinoma].

PMID- 15563074
TI  - [Progress in HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)].

PMID- 15563076
TI  - [Re-operation for thyroid carcinoma patients who received nonstandard operation].
AB  - OBJECTIVE: To analyze the reasons for re-operation and living condition of
      thyroid carcinoma patients who received second operation, and to formulate
      indications for selecting re-operation candidates and operation types. METHODS:
      One hundred and eleven thyroid carcinoma patients were retrospectively
      summarized. All patients received re-operation after thyroidectomy from 1986 to
      1997. The post operative follow-up data were analyzed statistically. RESULTS:
      Pathological results confirmed there were 67.6% (75/111) cases with residual
      tumor. The incidence rate of post-operative complications was 2.7%, including
      0.9% (1/111) recurrent laryngeal nerve injury. The sensitivity of residual
      carcinoma detection by CT scan before operations was 80.0% (28/35), with the
      positive predictive value of 87.5% (28/32). The recurrence rate within 3 years
      was 11.7% (13/111), with a local control rate of 88.3% (98/111). The recurrence
      rate within 5 years was 14.4% (16/111), with a local control rate of 85.6%
      (95/111). Life table was adopted to calculate living rates. The accumulated 5
      year and 10-year living rates of re-operated thyroid carcinoma patients were
      95.0% and 93.2% respectively. Analysis of Cox Regression showed that carcinoma
      recurrence influenced survival conditions significantly. CONCLUSIONS: The
      residual rate of re-operated patients with thyroid carcinoma was relatively
      higher, so a cautious re-operation was necessary. CT scan has a relatively higher
      positive predictive rate in detecting residual carcinoma, so it is necessary for
      screening right candidates for re-operation. Recurrence was the main factor that
      influenced patients' survival. So making proper indications, according to which
      to select patients who need re-operations will decrease the incidence of
      unnecessary operations.

PMID- 15563077
TI  - [Endoscopic thyroid gland surgery without carbon dioxide neck insufflation].
AB  - OBJECTIVE: To evaluate endoscopic thyroid gland surgery without carbon dioxide
      neck insufflation. METHODS: Sixteen patients with thyroid gland benign tumor,
      aged from 23-62 years, were selected and treated with endoscopic surgery. Eight
      cases received whole thyroid lobectomy and the other eight cases received partial
      thyroid lobectomy, the procedure was through a wall method or a single 2.0-3.0 cm
      horizontal skin incision. Among the 16 cases, 6 were thyroid adenoma and 10 were
      nodular goiter. RESULTS: All patients received endoscopic surgery, 2 cases with
      sub-clavicle approach and 14 cases with a single 2.0-3.0 cm horizontal skin
      incision approach. The recurrent laryngeal nerve and parathyroid glands were
      easily identified and preserved during operation, the operating time lasted from
      1.1 hours to 4.0 hours, no complication occurred, the postoperative cosmetic
      outcome was excellent. CONCLUSIONS: The results indicated that gasless technique
      is feasible and safe, so it suggested that the video-assisted thyroid surgery
      without carbon dioxide neck insufflation could be an alternative for thyroid
      gland surgery.

PMID- 15563078
TI  - [Surgical treatment of thyroid carcinoma with the upper mediastinal invasion].
AB  - OBJECTIVE: To study the surgical management of the thyroid carcinoma with the
      upper mediastinal invasion. METHODS: Among the 560 thyroid carcinoma cases
      receiving surgery from 1988 to 1999, there were 10 cases of the upper
      mediastinal, the 10 cases were retrospectively analyzed for their preoperative
      diagnosis, surgical methods and postoperative complications. RESULTS: The upper
      mediastinal invasion rate of the 560 cases was 1.9% (10/516). There are three
      paths for the upper mediastinal invasion: (1) Trachea esophagus groove and upper
      mediastinal lymphatic node metastasis. (2) Tumor direct invasion. (3) Primary
      malignant substernal goiter. Operative methods include: (1) Tumor removal without
      using sternum incision. (2) Tumor removal with sternotomy. (3) Extension
      operation with sternum or/and clavicle bones removal. The number of those cases
      who survived 1, 3, 5, 10 years were 10, 8, 6, 4 respectively. Radical removal of
      tumors was achieved in 9 cases. The complications occurred were: 2 cases of
      chylous fistula; 2 cases of vocal paralysis; 1 case of thyrocervical trunk artery
      bleeding; 1 case of phrenic nerve paralysis; 1 case of pneumothorax. CONCLUSIONS:
      Surgery can be adopted for treating thyroid carcinoma with the upper mediastinal
      invasion, and it can have a good long-term prognosis.

PMID- 15563079
TI  - [Nerve exploration and decompression for traumatic recurrent laryngeal nerve
      injuries induced by thyroid gland surgery].
AB  - OBJECTIVE: To show the findings of recurrent laryngeal nerve injury exploration
      and find out therapeutic effects, indications and timing of nerve decompression
      for traumatic recurrent laryngeal nerve injury induced by thyroid gland surgery.
      METHODS: In this study there were 87 patients with recurrent laryngeal nerve
      injury, including 65 for nerve exploration and 22 for nonsurgical treatment.
      During nerve exploration, the types, severity of laryngeal nerve injuries and
      laryngeal muscular mass were studied. Nerve decompression was performed in these
      14 patients whose compressing sutures or compression due to cicatricial
      hypertrophy were received nerve decompression. RESULTS: Injuries caused by
      thyroid gland operations mostly are of suture ligation (43%) and nerve severance
      (48%); simple scar compression was found only in 6 cases (9%). Atrophy of the
      laryngeal muscles was not very serious in patients with a course less than 6
      months. In 10 patients with a course less than three months, nerve decompression
      restored normal functional abductor and abductor motion of the vocal cord in 9
      patients and had no effects in one. Although functional motion of vocal cord was
      not seen in one case with a course less than 3 months and 4 cases between 3 and 5
      months, the mass and tension of the reinnervated vocal cord became much the same
      as the contralateral normal vocal cord, thus resuming symmetric vibration of the
      vocal cords and physiological phonation. Although nonsurgical treatment improved
      severe hoarseness, it didn't restore normal functional motion of the vocal cord
      and normal voice. CONCLUSIONS: Nerve exploration showed a primary rule for
      recurrent laryngeal nerve injury induced by thyroid gland surgery. Early and mid
      stage recurrent laryngeal nerve exploration and decompression may restore normal
      motion of the glottis, and it suggested laryngeal delayed reinnervation may help
      patients with a course more than 6 months.

PMID- 15563080
TI  - [Connection of efferent neurons and afferent vestibular nuclei in rat].
AB  - OBJECTIVE: To study the connection between the efferent and afferent vestibular
      neurons in the center neural system. METHODS: In the present study, a retrograde
      neuron tracer horseradish peroxidase (HRP) was injected into the surrounding of
      efferent vestibular neurons located in the inner side of the facial genu of the
      rat and after following 48 hours for the retrograde axonal transport of this
      tracer, then its presence in neurons of the brain stem was demonstrated
      histochemically. RESULTS: Neurons labeled with HRP were found bilaterally in both
      Medial vestibular nuclei (MVe) and lateral vestibular nuclei (LVe). Approximately
      80% of the neurons in each were located in the MVe on the side ipsilateral to the
      injection. CONCLUSIONS: There is a direct connection between the efferent and
      afferent vestibular neurons. These findings suggest that there is an afferent
      efferent feedback regulatory mechanism in the vestibular system.

PMID- 15563081
TI  - [Study of sensitivity to impulse noise in guinea pig, rat and mouse].
AB  - OBJECTIVE: To study sensitivity to impulse noise in guinea pig, rat and mice.
      METHODS: Six groups were divided. Group I: Guinea pigs (n = 5) were exposed to 50
      impulses of 160 dB SPL; Group II: Guinea pigs (n = 5) were exposed to 100
      impulses of 160 dB SPL; Group III: Guinea pigs (n = 5) were exposed to 200
      impulses of 160 dB SPL; Group IV: Guinea pigs (n = 6) were exposed 400 impulses
      of 160 dB SPL; Group V: Rats (n = 10) were exposed to 50 impulses of 160 dB SPL;
      Group VI: Mice (n = 10) were exposed to 50 impulses of 160 dB SPL. ABR thresholds
      were determined prior to, immediately, one day, one week, two weeks and four
      weeks after impulse noise exposure. RESULTS: The rat and mice were shown
      temporary threshold shift (TTS) and permanent threshold shift (PTS) after 50
      times impulse noise (160), while no TTS and PTS in the guinea pigs but it was
      shown TTS and PTS after 400 times impulse noise (160). CONCLUSIONS: Sensitivity
      to impulse noise is different among guinea pig, rat and mouse. Guinea pig has
      less sensitivity to impulse noise while rat and mouse have higher sensitivity to
      impulse noise. In addition, rat has higher sensitivity to impulse noise than
      mouse.

PMID- 15563082
TI  - [Expression of aquaporin-1 and Bcl-2 mRNA in eosinophils of the nasal polyps and
      its significance].
AB  - OBJECTIVE: To study the significance of aquaporin-1 (AQP-1) expression in the
      eosinophils of nasal polyps. The expression and location of AQP-1 mRNA and
      apoptosis associated gene Bcl-2 mRNA in nasal polyps were explored. METHODS:
      Sixteen nasal polyp samples were collected from 11 women and 5 men aged 20-65
      years during routine endonasal surgery. Nasal mucosa specimens from the inferior
      turbinates of 10 patients with allergic rhinitis (7 women and 3 men, aged 16-58
      years), collected during septoplasty, were used as controls. The expression of
      AQP-1 mRNA and Bcl-2 mRNA was detected in serial adjacent sections by in situ
      hybridization and eosinophils were examined by stain MGG. RESULTS: AQP-1 mRNA
      expression was found in all 16 nasal polyps and in 4 of 10 inferior turbinate
      tissues, the mean expression rates were (93.16 +/- 13.25)% and (19.54 +/- 4.98)%,
      respectively. All 16 nasal polyps and 10 control nasal tissues expressed Bcl-2
      mRNA, by the average rates of (84.74 +/- 12.10)% and (16.45 +/- 3.12)%,
      respectively. The expression of AQP-1 mRNA was positively correlated with Bcl-2
      mRNA expression in nasal polyps (r = 0.875, P < 0.01). CONCLUSIONS: AQP-1
      contributes to the survival of eosinophils in nasal polyps by keeping the
      permeation balance of eosinophils.

PMID- 15563083
TI  - [Relationship between GATA-3 and IL-4 and IL-5 in patients with allergic
      rhinitis].
AB  - OBJECTIVE: To evaluate the relationship between GATA-3 and IL-4, IL-5 in patients
      with allergic rhinitis. METHODS: The expression of GATA-3 was detected by
      immunochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) in
      23 patients with allergic rhinitis. IL-4, IL-5 were detected by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The positive rate of GATA-3 was 86.9%
      (20/23) and the relative density ratio of GATA-3 and glyceraldehyde phosphate
      dehydrogenase (GAPDH) were 0.602 +/- 0.11 in patients with allergic rhinitis. The
      concentrations of IL-4, IL-5 were (135.5 +/- 66.4) pg/mg, (77.5 +/- 29.4) pg/mg,
      respectively. The expressions of GATA-3 and IL-4, IL-5 had positive relationship
      (r = 0.45 and 0.62, P < 0.05). CONCLUSIONS: GATA-3 contributed to the production
      of IL-4, IL-5 in patients with allergic rhinitis.

PMID- 15563084
TI  - [Characteristics of the response of vestibular evoked myogenic potentials to
      different stimulus modes].
AB  - OBJECTIVE: Vestibular evoked myogenic potential (VEMP) has been utilized in
      clinic to test the function of saccule. In the present study, 3 stimulus modes
      were applied to 21 normal adults and intended to draw in a clinical test
      protocol. METHODS: The normal latency and amplitude of VEMPs of 21 normal
      subjects were recorded and the ratio of bilateral amplitudes and asymmetry were
      calculated. RESULTS: The response to binaural clicks were similar to the response
      of the monaural clicks. The interindividual variation in amplitude were large,
      but the latency varied little. CONCLUSIONS: VEMPs is a stable myogenic
      potentials. Monaural and binaural clicks stimulus can be used in clinical
      practice. The latter is appropriate for normal hearing subjects. Amplitude
      measurement is probable to evaluate the asymmetry of bilateral saccular function
      and may reveal saccule lesion.

PMID- 15563085
TI  - [Inferior vestibular nerve impairment in auditory neuropathy].
AB  - OBJECTIVE: To investigate if auditory neuropathy have inferior vestibular nerve
      (IVN) lesion and to explore the relation between AN and the IVN lesion by
      vestibular evoked myogenic potentials (VEMPs). METHODS: VEMPs were observed in 13
      patients with auditory neuropathy. And the relation among the duration, hearing
      threshold of lower frequency and speech discrimination score with VEMPs were
      observed. RESULTS: Fifty-four percent patients in auditory neuropathy had
      abnormal VEMPs. They took the form of lower amplitude and no response. The
      statistical analysis showed that the abnormality of VEMPs had no correlation with
      lower frequency hearing loss, the duration and speech discrimination score.
      CONCLUSIONS: The IVN dysfunction may coexist with auditory neuropathy, having
      lesion in the IVN. However, there was no significant relation between the
      severity of AN and VEMPs, which meant that AN and inferior vestibular neuropathy
      had their independence to some extent.

PMID- 15563086
TI  - [Expression and DNA binding activity of NF-kappaB in mucosal tissue of chronic
      rhinosinusitis].
AB  - OBJECTIVE: To study the expression and activation of nuclear factor-kappa B (NF
      kappaB) in mucosa of rhinosinusitis. METHODS: The expressions of NF-kappaB p50
      and p65 in the mucosa from 18 patients and 10 norms were detected with the method
      of immunohistochemistry. The activation of DNA-binding proteins which was
      labelled with 32P-radiolabeled oligonucleotide probe for NF-kappaB was detected
      with electrophoretic mobility shift assays (EMSA) in mucosa. RESULTS: Plasma of
      epithelial and glandular cells displayed a strongly positive staining reaction to
      p65, and nucleus displayed a strongly positive staining reaction to p50 (7.8%
      52.1%). There was significantly difference (chi2 = 22.917, P < 0.01). The DNA
      binding proteins activity of 18 samples from patients with chronic rhinosinusitis
      (28.14 +/- 16.71) was stronger than that (9.28 +/- 2.84) in normal subjects (t =
      4.56, P < 0.05). CONCLUSIONS: The expression and DNA-binding proteins activity of
      NF-kappaB was enhanced. It indicated that NF-kappaB was activated in mucosal
      inflammation of chronic rhinosinusitis.

PMID- 15563087
TI  - [Olfactory function and olfactory marker protein in patients with chronic
      sinusitis].
AB  - OBJECTIVE: To study the pathogenesis of dysosphresia in patients with chronic
      sinusitis, to discuss the expression and significance of olfaction marker protein
      in olfactory mucosa. METHODS: There were 55 cases with chronic sinusitis in the
      experimental group, and 11 cases in the control. All of them were first tested by
      subjective method, and then the olfactory marker protein in olfactory mucosa was
      examined by the method of immunohistochemistry. Tissue sections were observed
      under optical microscope. RESULTS: The ratio of dysosphresia in patients with
      chronic sinusitis was 50.9% (28/55), while by subjective olfactory test, it was
      85.5% (47/55). The ratio of dysosphresia in control patients was 9.09% (1/11), by
      subjective olfactory test, it was 18.2% (2/11). Olfactory marker protein was
      identified in the olfactory cells and microvillar cells by histochemical and
      immunohistochemical technique (S-P method). CONCLUSIONS: The main cause of
      dysosphresia in patients with chronic sinusitis is the decrease, atrophy and
      degeneration of the olfactory cells, which lead to the failure of olfactus
      perception and recognition.

PMID- 15563088
TI  - [Treatment of pediatric obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To evaluate treatment options of pediatric obstructive sleep apnea
      hypopnea syndrome (OSAHS) and their curative effect. METHODS: In this study,
      there are 59 confirmed pediatric obstructive sleep apnea hypopnea syndrome cases
      diagnosed by polysomnography (PSG). Among them, 54 cases were treated by
      tonsillectomy or/and adenoidectomy directed by transoral endoscopy. Continue
      positive airway pressure (CPAP) was used for 2 cases in long-term. Three cases
      were treated with other conservative therapy. OSA-18 (quality of life for
      children with obstructive sleep apnea 18 items) was adopted as a disease-specific
      quality-of-life follow-up survey before and after treatment. RESULTS: During
      perioperation period, no postoperative bleeding or acute respiratory obstruction
      occurred. Follow-up sleep study was carried out 12-18 months postoperatively, no
      complications of velopharyngeal insufficiency, nasopharyngeal stenosis or
      residual adenoid were found. OSA-18 scores showed that quality of life had been
      significant improved after operation in 76.3% (45 cases), sleep disturbance in
      88.1% (52 cases) and physical symptoms in 67.8% (40 cases). The pressure level of
      long-term CPAP in 2 cases was about 5.6-7.8 cmH2O. 3 cases were slightly improved
      treated with conservative therapy. CONCLUSIONS: Surgical removal of upper airway
      obstruction caused by enlargement of tonsil and adenoid is one of the most
      effective treatment for pediatric OSAHS. Fibrous endoscopy and cephalometric
      analysis are helpful to confirm surgical indication. The advantages of transoral
      endoscopy directed adenoidectomy are as follows: clear and direct visualization,
      complete removal, without damaging of the peripheral structures.

PMID- 15563089
TI  - [Gene expression of matrix metalloproteinase 14 in laryngeal squamous cell
      carcinoma].
AB  - OBJECTIVE: To investigate the role of expression of matrix metallo-proteinase 14
      (MMP14) in laryngeal carcinomas and the relationship between MMP14 expression and
      the laryngeal biological behavior. METHODS: The gene expression differences of
      MMP14 between fresh laryngeal cancer tissues and their surrounding normal mucosa
      was analyzed by RT-PCR. The expression of MMP14 protein in paraffin-embedded
      tissues was determined immunohistochemically. All statistical analyses were
      performed by SPSS version 10.0. RESULTS: In the 33 cases of matched specimens,
      MMP14 gene expression was much higher in tumor tissues than that in surrounding
      ing normal tissues in 26 cases and lower in 2 cases, whereas in other 5 cases, no
      significant difference was observed between the cancer tissue and the surrounding
      normal tissue. MMP14 gene expression was not different in different stages in
      laryngeal glottic cancers, but correlated to the differentiation and lymph node
      metastasis (P < 0.05). There was correlation between MMP14 gene expression and
      the stage, differentiation and lymph node metastasis in the laryngeal
      supraglottic cancers (P < .05). MMP14 protein was localized predominantly in the
      carcinoma cell cytoplasm and in the stromal fibroblast cytoplasm, and weakly or
      not expressed in surrounding normal tissue. MMP14 protein expression was much
      higher in tumor tissue than that in surrounding normal tissue in most of the
      cases. In general, MMP14 protein expression was the same as MMP14 gene expression
      and related to the stage, differentiation and lymph node metastasis in the
      laryngeal cancers. There was no survival difference at 3, 5 and 7-year between
      the group with higher MMP14 protein expression in tumor tissues than surrounding
      normal tissues and the group with no difference of MMP14 protein expression (Log
      Rank, P=0.5535). CONCLUSIONS: The protein MMP14 may play role in laryngeal cancer
      invasion in a certain extent, but important role in lymph node metastasis of
      laryngeal cancer. The over-expression of MMP14 protein may be a marker for lymph
      node metastasis of laryngeal cancer.

PMID- 15563091
TI  - The state of sex education in American schools.

PMID- 15563090
TI  - Sex, drugs, and delinquency in urban and suburban public schools.

PMID- 15563092
TI  - Childhood obesity--what the research tells us.

PMID- 15563093
TI  - Baked chips, pretzels and low fat cookies are not healthy choices.

PMID- 15563094
TI  - Developing diabetes training programs for school personnel.

PMID- 15563095
TI  - The use of food by teachers.

PMID- 15563096
TI  - Vending machines in schools: what are we to do?

PMID- 15563097
TI  - Neurofibromatosis type 1.

PMID- 15563098
TI  - Which one is me?

PMID- 15563099
TI  - Treating sudden cardiac arrest in a school setting.
AB  - Sudden cardiac arrest occurs when the heart's electrical system fires very
      rapidly and in an uncoordinated manner, rendering the heart incapable of pumping
      blood through the circulatory system. The heart begins to tremble uncontrollably,
      like a quivering bowl of jelly. The victim becomes unconscious, stops breathing,
      and typically has no pulse or signs of circulation. Unless this condition is
      reversed, death follows in a matter of minutes. Defibrillation ("shocking a
      patient") is the only effective means of re-setting the heart's normal electrical
      impulses.

PMID- 15563100
TI  - A poisoning can happen to you... at any age.

PMID- 15563101
TI  - Make brushing fun for little ones. Tips for promoting good oral hygiene habits in
      kids.

PMID- 15563102
TI  - Morphology of the air sacs (sacci pneumatici) in the rock partridge (Alectoris
      graeca).
AB  - The aim of the study was to describe the air sacs of the rock partridge. The sacs
      of 15 adult birds were cast by injection of latex via the trachea and then
      corroded with 30% KOH at 40 degrees C. The morphology of the sacs was in general
      similar to that of other avian species described in the literature. There were,
      however, significant characteristics such as an additional subcutaneous
      diverticulum of the cranial thoracic sac and a caudally pointing diverticulum of
      the cervical sac located between the lungs.

PMID- 15563103
TI  - Listeria monocytogenes in products of animal origin in Turkey.
AB  - A study was carried out on 430 samples of different foodstuffs (soft cheese, raw
      chicken, minced beef, sausage, fish) and 400 carcase samples (sheep, young and
      adult cattle) for screening of Listeria monocytogenes. It was found that only one
      of the samples contained L. monocytogenes at > 10(3) cfu/ml in the initial
      examination, but another 42 samples contained L. monocytogenes following an
      enrichment process. L. monocytogenes was isolated most frequently from raw
      chicken samples (18%), but was not isolated from sausage samples. Forty-three
      isolates were defined as serotypes by using Bacto-Listeria-O-antisera Type 1
      (Difco 2300-50-2) and Type 4 (Difco 2301-50-1) except that Type poly was not
      used. For these reasons, all isolates were classified as type 1 or type 4 and the
      other was termed untypeable. Twenty-one samples were type 1, 17 were untypeable,
      and 5 were both serotype 4 and untypeable.

PMID- 15563104
TI  - Humoral and delayed-type hypersensitive responses against listeria monocytogenes
      phosphatidylinositol-specific phospholipase C in experimentally infected
      buffaloes.
AB  - The kinetics of antibody production against phosphatidylinositol-specific
      phospholipase C (PI-PLC) and the isolation pattern of Listeria monocytogenes from
      bacteriological samples were studied following oral infection of buffalo calves
      with 3 x 10(9) cells each of pathogenic L. monocytogenes. Antibodies to PI-PLC
      appeared by 4-8 days post infection (PI), with a peak between days 7 and 16 PI,
      when tested by indirect plate-ELISA. Subsequently, antibody titres in all the
      animals declined and became undetectable on days 26-35 PI onwards until the study
      concluded on day 211 PI. Dot-ELISA could detect the antibodies to PI-PLC 1-2 days
      earlier and at higher titres as compared to plate-ELISA. L. monocytogenes could
      be recovered from faeces, nasal swabs and haemocultures from days 2 to 33, days 2
      to 21 and days 11 to 17 PI, respectively. Antibodies to PI-PLC were detected
      during the course of active infection but their titres declined sharply once
      animals became culturally negative. Sonicated antigen elicited the highest
      delayed-type hypersensitivity response, followed by PI-PLC and listeriolysin O.

PMID- 15563105
TI  - Evaluation of a PCR based on primers to Nc5 gene for the detection of Neospora
      caninum in brain tissues of bovine aborted fetuses.

PMID- 15563106
TI  - Mode of binding of fibrinogen, fibronectin and iron-binding proteins by animal
      enterococci.
AB  - Sixty-two animal enterococci were examined for their binding of bovine
      fibrinogen, porcine fibronectin, bovine lactoferrin, bovine apotransferrin and
      human holotransferrin in the particle agglutination assay (PAA). Individual
      strains expressed binding of selected glycoproteins to various degrees (0, 1, 2,
      3), whereas bovine fibrinogen binding of enterococci from goats, rabbits and
      rodents was the strongest (3) in general. Porcine fibronectin was bound weakly (1
      or 2) by enterococci from horses, dogs, poultry, rabbits and rodents, while most
      of the goat isolates and half of the dog feed isolates did not bind fibronectin
      (0). Bovine lactoferrin was bound especially by the isolates from rodents and
      rabbits. Bovine apotransferrin was bound very weakly (1) by only a few isolates.
      Human holotransferrin was bound to a greater extent than apotransferrin by some
      isolates from rabbits and rodents. Since multiresistant strains are preferred in
      our binding studies, enterococci were also examined for their antibiotic
      resistance pattern. Almost all investigated isolates were resistant at least to
      one antibiotic. However, some strains displayed resistance to five or six
      antibiotics of 10 antibiotics tested. In a study of the inhibitory effect of
      heparin, porcine mucin and hyaluronic acid, the greatest effect was observed
      after heparin treatment of bacterial cells. These observations, as well as the
      expression of heparin binding by most strains, may suggest that at least one mode
      of enterococcal attachment utilizes glycosaminoglycan chains present on the
      surface of adherent cells.

PMID- 15563107
TI  - Comparative pharmacokinetics and bioavailability of amoxycillin in chickens after
      intravenous, intramuscular and oral administrations.
AB  - The pharmacokinetics and systemic bioavailability of amoxycillin were
      investigated in clinically healthy, broiler chickens (n = 10 per group) after
      single intravenous (i.v.), intramuscular (i.m.), and oral administrations at a
      dose of 10 mg/kg body weight. The plasma concentrations of amoxycillin were
      determined using high-performance liquid chromatography (HPLC) and the data were
      subjected to compartmental and non-compartmental kinetic analyses. Following
      single i.v. injection, all plasma amoxycillin data were described by a two
      compartment-open model. The elimination half-lives of amoxycillin were 1.07 h,
      1.09 h and 1.13 h after single i.v., i.m. and oral administration, respectively.
      The total body clearance (Cl(B)) of amoxycillin was 0.80 (L/h)/kg and the volume
      of distribution calculated as V(d(area)) was 1.12 L/kg, respectively after i.v.
      administration. Substantial differences in the resultant kinetic data were
      obtained by comparing the plasma concentration profiles after i.m. injection with
      that after oral administration. The systemic i.m. bioavailability of amoxycillin
      was higher (77.21%) than after oral (60.92%) dosing. In vitro, the mean plasma
      protein binding of amoxycillin amounted to 8.27%. Owing to high clearance of
      amoxycillin in birds in our study, a plasma level was maintained above 0.25
      microg/ml for only 6 h after i.m. and oral routes of administration and
      consequently frequent dosing may be necessary daily.

PMID- 15563108
TI  - Clinical and pathological aspects of experimental oleander (Nerium oleander)
      toxicosis in sheep.
AB  - Dried Nerium oleander leaves at single lethal dose of 110 mg/kg body weight were
      administered orally to six native male sheep. Clinical signs of toxicosis in
      sheep began to appear about 30 min after receiving the oleander and included
      decrease of the heart rate followed by cardiac pauses and tachyarrhythmias;
      ruminal atony, mild to moderate tympany, abdominal pain, polyuria and polakiuria.
      Electrocardiography revealed bradycardia, atrio-ventricular blocks, depression of
      S-T segments, ventricular premature beats and tachycardia, and ventricular
      fibrillation. Five sheep died within 4-12 h and one survived. At necropsy there
      were varying degrees of haemorrhages in different organs and gastroenteritis.
      Histopathological examination of tissue sections revealed myocardial degeneration
      and necrosis, degeneration and focal necrosis of hepatocytes, necrosis of tubular
      epithelium in kidneys, oedema in the lungs, and ischemic changes in the cerebrum.

PMID- 15563109
TI  - Usefulness of polymerase chain reaction in early detection and tissue tropism of
      fowl adenovirus in experimentally infected chicken.

PMID- 15563110
TI  - Production and characterization of monoclonal antibodies to peste des petits
      ruminants (PPR) virus.
AB  - Peste des petits ruminants (PPR) is an acute, febrile viral disease of small
      ruminants, caused by a virus of the genus Morbillivirus. PPR and rinderpest
      viruses are antigenically related and need to be differentiated serologically. In
      the present study, 23 mouse monoclonal antibodies were produced by
      polyethyleneglycol (PEG)-mediated fusion of sensitized lymphocytes and myeloma
      cells. Among these, two belong to the IgM class and the remaining 21 to various
      subclasses of IgG. The MAbs from the IgG class designated 4B6 and 4B11
      neutralized PPR virus in vitro. In radioimmunoprecipitation assay, 10 MAbs
      recognized nucleoprotein, 4 recognized the matrix protein and one each
      haemagglutinin and phosphoprotein. The remaining 7 MAbs failed to precipitate any
      defined viral protein. The reactivity pattern of the monoclonal antibodies in
      indirect ELISA indicated a close antigenic relationship within three Indian PPR
      (lineage 4) virus isolates and also within two rinderpest vaccine strains. All
      PPR virus isolates could be distinguished from rinderpest vaccine viruses on the
      basis of the reactivity pattern of all MAbs and anti-N protein MAbs. A set of six
      monoclonal antibodies specific to PPR virus could also be identified from the
      panel. From the panel of MAbs available, two MAbs were selected for diagnostic
      applications, one each for the detection of antigens and antibodies to PPR virus.

PMID- 15563111
TI  - Sequence analysis of an Indian field isolate of infectious bursal disease virus
      shows six unique amino acid changes in the VP1 gene.

PMID- 15563112
TI  - [Compendium of surgery].
AB  - The sane authors of the work titled "Treaty of Pathology and Surgical Clinic" of
      the Editorial McGraw-Hill Iberoamericana written in three volumes, of those that
      have been carried out several reprints and a second edition with changes in the
      structure and contents, that it has been accepted by studious of the surgery in
      spain and other countries, have the mission of writing this book whose extension
      constitutes approximately the third part of the Treaty os Surgery mentioned. The
      object of this work that contains the whole General Surgery and their
      specialities, as it corresponds to the effective university programs, it is to
      define the extension of matters at the postgraduates' level, instead of being
      also good for postgraduates and incipient specialist with the purpose of that the
      students are not overflowed when facing at the same time with other disciplines
      in each course. The spirit of this book has much of the one that feeds the
      persons that write, all of them Professors of Pathology and Surgical Clinic that
      believe in General Surgery and they exercise it, naturally with personal
      preferences toward the different sectors of the same one, as it is done in almost
      all countries.

PMID- 15563113
TI  - [Injuries in children].
AB  - It is underlined the great importance of accidents, as they present with high
      frequency, account for a large number of deaths and suffering and have deep
      economic costs. During last years the prevention of accidents has notably
      reduced, their frequency and negative outcomes. However, remarkable differences
      exist across the European Union countries. Thus, it should be emphasized the
      importance of implementing, more and better, all kind of preventive measures.

PMID- 15563114
TI  - [Towards an unified theory of the universe basic forces ("the everything
      theory")].
AB  - Numerous efforts have been made in order to unify all the basic forces in nature.
      In 1967 the fusion of electromagnetic and weak forces was obtained and in 1973 a
      theoretical bridge between the electroweak and the strong forces have been
      constructed. This theory is waiting for experimental proofs in the CERN large
      hadron collider. The last stage would be "the everything theory", which includes
      the gravitational force. Only the so called superstring theory is a good
      candidate to overcome the incompatibility of the quantum mechanics and the
      general relativity, but this theory is not already achieved.

PMID- 15563115
TI  - [Eulogy of Dr. Carlos Zurita Delgado].

PMID- 15563116
TI  - [Considerations on the evolution of the electrocardiography].

PMID- 15563117
TI  - [Eulogy of Prof. Dr. Robert W. Jackson].

PMID- 15563118
TI  - Arthroscopy: the catalyst for minimally invasive surgery.

PMID- 15563119
TI  - [Severe acute respiratory syndrome and avian flu].
AB  - Severe acute respiratoru syndrome (SARS) is a new disease that caused large
      ourbreaks in several countries in the first half of 2003, resulting in infection
      in more than 8.000 people and more than 900 deaths. The disease originated in
      southern China and a novel coronavirus (SARS CoV) has been implicated as the
      causative organism. We present an overview of the etiology, clinical presentation
      and diagnosis, based on the current state of knowledge derived from published
      studies and our experience in the National Microbiology Centre. Influenza is a
      zoonosis. This appreciation of influenza ecologyfacilitated recognition of the
      H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an
      incipient pandemic situation, the chicken being the source of virus for humans
      and. The current outbreak of avian influenza in South East Asia has resulted in a
      small number of human deaths. These findings highlight the importance of
      systematic virus surveillance of domestic poultry in recognizing changes in virus
      occurrence, host range and pathogenicity as signals at the avian level that could
      presage a pandemic.

PMID- 15563120
TI  - [Epidemiological perspectives on SARS and avian influenza].
AB  - SARS is a respiratory infection caused by Coronavirus (Nidoviruses, RNA) from
      which 3 groups are known. Group 1 affects dogs, cats, pigs, and the human agent
      is 229 E. Group 2 affects bovines or rodents, and the human agent is OC43. And
      group 3 corresponds to the avian pathology.... The epidemics emerged on February
      2003 in Guangdong, South China, due to consumption of exotic animals (Civeta,
      etc.), and it spread through interperson contagion to other regions in Asia,
      America and Europe. Incubation period is about 2-7 days. Transmission Of the
      virus is person-to person, but also by excretions and residual water. Basic
      reproductive rate is 2 to 4, and it is considered that 2.7 persons are infected
      from the initial case. In June 2003, SARS affected over 8,000 people and 774 were
      killed. Mortality approaches to 10%, and it is higher among older people rising
      up to 50% in those aged over 65 years. It is important to quickly establish
      action protocols regarding clinical, epidemiological and prevention aspects.
      Avian influenza is an infection caused by type A Influenza Orthomixovirus, in
      which migration birds and wild ducks are the main reservoir. Avian viruses
      correspond to H5, H7, H9. In 1997 it was observed that type AH5N1 jumped
      interspecies barrier and affected 18 humans, and 6 of them died. At the end of
      2003 and in 2004 this type of poultry flu was described in Asia. FAO has
      emphasized that sacrifice of chicken in affected farms is the most effective
      measure to fight against the disease. It has also been established suppression of
      imports from these countries. There is no evidence on interperson contagion from
      chicken contagion, nor on food-borne contagion to humans.

PMID- 15563121
TI  - [Present data on influenza virus isolated from ducks and chickens, and influenza
      virus C. Anti-influenza drugs].
AB  - Present data on influenza virus isolated from ducks and chickens, and influenza
      virus C. Anti-influenza drugs. Within the broad field of Glycopathology and
      Glycotherapeutics, research on influenza virus types A, B and C from humans and
      several bird species (particularly migratory birds such as ducks, since they are
      reservoirs for viruses), as well as the search for improved drugs designed for
      the prevention or treatment of epidemics/pandemics produced by most of those
      viruses are issues of relevant interest not only from a scientific point of view
      but also for repercussions on health and the important economical consequences.
      The research work begun by the author and collaborators at the Department of
      Biochemistry and Molecular Biology of the University of Salamanca (Spain) in the
      middle of the 1970's, developed later in close cooperation with the "(Unite
      d'Ecologie Virale" of the Pasteur Institute of Paris (Prof. Claude Hannoun and
      collaborators), has been published in about twenty papers that mainly focus on
      the theoretic-experimental study of: The sialidase (neuraminidase) activity of
      human influenza viruses types A and B. The acetylesterase activity of type C
      virus from humans and dogs. The sialidase activity of type A virus from ducks and
      pigs, in comparison with that of humans. Certain sialidase inhibitors as useful
      anti-influenza drugs, especially in the case of possible future influenza
      pandemics of avian origin.

PMID- 15563122
TI  - [Balmis and the philanthropic expedition of the vaccine. Bicentennial of the
      Royal Philanthropic Expedition of Francisco Xavier Balmis to carry smallpox
      vaccine to America and Philippines].

PMID- 15563123
TI  - [Historical profile of Spanish medicine].
AB  - In this essay what we try to explain is that, according te the historical
      evolution of the peninsular Medicine, we can diatinguish a first pre-Hispanic
      period where the important Hispano-Arabian medical heritage and its transmission
      to the Cristian Europe are included. The real Spanish Medicine, which started
      when the unification of the peninsular Kingdoms made by the Catholic Queen and
      King took place, goes through splendour and decadence periods, showring its
      relationship with concrete national political situations and war episodes, which
      caused the lack of concordance between our medicine and the historical
      development of the European Medicine.

PMID- 15563124
TI  - Immunogenic peptides generated by frameshift mutations in DNA mismatch repair
      deficient cancer cells.
AB  - About 15% of all human colorectal, gastric, and endometrial tumors, and the
      majority of tumors in patients suffering from hereditary nonpolyposis colorectal
      cancer syndrome, are caused by loss of DNA mismatch repair functions. In the
      affected cancer cells, this results in insertion or deletion mutations at short,
      repetitive DNA sequences referred to as microsatellites. Such mutations in coding
      microsatellites (cMS) cause translational frameshifts that may destroy gene
      function. These frameshift mutations could also cause the translation of
      immunogenic neopeptides at the carboxy terminus. Several such mutations have been
      identified recently. However, since none of the frameshift-induced neopeptides
      identified so far is generated in all cancer cells with microsatellite
      instability (MSI), we aim to define a broad but comprehensive set of frameshift
      peptides (FSPs) that might be combined in a multivalent vaccine for MSI+ cancers.
      Here, we characterize the immunogenic properties of five additional HLA-A0201
      restricted frameshift-induced neopeptides derived from mutations in three cMS
      containing genes (Caspase-5, TAF-1b, and HT001) that are frequently hit in MSI+
      cancer cells. One Caspase-5-derived FSP, (67)-FLIIWQNTM (FSP26), was identified
      as a novel HLA-A0201-restricted CTL epitope. FSP26-specific CTLs efficiently
      lysed colon carcinoma cells expressing HLA-A0201 and the underlying (-1)
      mutation. This mutation in an A(10) cMS is observed in up to 66% of MSI+
      colorectal cancers. Thus, this newly identified CTL epitope may be another
      essential component of a multivalent vaccine against cancers with MSI.

PMID- 15563125
TI  - Solid-state 17O NMR as a probe for structural studies of proteins in
      biomembranes.
AB  - We report the first example of 17O NMR spectra from a selectively labeled
      transmembrane peptide, 17O-[Ala12]-WALP23, as a lyophilized powder and
      incorporated in hydrated phospholipid vesicles. It is shown that at high magnetic
      field it is feasible to apply 17O NMR to the study of membrane-incorporated
      peptides. Furthermore, we were able to estimate distances within the selectively
      labeled WALP peptide, which represents a consensus transmembrane protein
      sequence. This work opens up new applications of 17O solid-state NMR on
      biological systems.

PMID- 15563126
TI  - Synthesis, crystal structure, and transistor performance of tetracene
      derivatives.
AB  - The substitution of chloro or bromo groups in tetracene gives rise to the change
      of crystal structure, having a substantial effect on carrier transport.
      Halogenated tetracene derivatives were synthesized and grown into single
      crystals. Monosubstituted 5-bromo- and 5-chlorotetracenes have the herringbone
      type structure, while 5,11-dichlorotetracene has the slipped pi stacking
      structure. Mobility of 5,11-dichlorotetracene was measured to be as high as 1.6
      cm2/V.s in single-crystal transistors. The pi stacking structure, which enhances
      pi orbital overlap and facilitates carrier transport, may thus be responsible for
      this high mobility.

PMID- 15563127
TI  - Thermal and photochemistry of a pyrene dihydrodioxin (PDHD) and its radical
      cation: a photoactivated masking group for ortho-quinones.
AB  - Pyrene dihydrodioxins (1 and 2) have been synthesized and shown to be effective
      photochemical blocking groups for pyrene-4,5-dione (3). The mechanism of quinone
      release proceeds through the formation of a remarkably stable radical cation.
      Direct evidence is provided that this radical cation is not only thermally labile
      but also photochemically labile, and that both pathways lead to quinone
      extrusion. Once initiated with UV light, the pyrene quinone product serves as an
      electron-transfer photosensitizer for the further release of quinone with visible
      light.

PMID- 15563128
TI  - Mesostructured selenides with cubic MCM-48 type symmetry: large framework
      elasticity and uncommon resiliency to strong acids.
AB  - The metal mesostructured Pt/Sn/Se chalcogenides with cubic MCM-48 type pore
      symmetry are found to be surprisingly stable in concentrated oxidizing acids.
      Their metal chalcogenide framework exhibits high flexibility during reversible
      proton exchange as it expands and contracts in an apparent breathing-like action.

PMID- 15563129
TI  - A molecular spring for vision.
AB  - Light absorption by the visual pigment rhodopsin leads to vision via a complex
      signal transduction pathway that is initiated by the ultrafast and highly
      efficient photoreaction of its chromophore, the retinal protonated Schiff base
      (RPSB). Here, we investigate this reaction in real time by means of unrestrained
      molecular dynamics simulations of the protein in a membrane mimetic environment,
      treating the chromophore at the density functional theory level. We demonstrate
      that a highly strained all-trans RPSB is formed starting from the 11-cis
      configuration (dark state) within approximately 100 fs by a minor rearrangement
      of the nuclei under preservation of the saltbridge with Glu113 and virtually no
      deformation of the binding pocket. Hence, the initial step of vision can be
      understood as the compression of a molecular spring by a minor change of the
      nuclear coordinates. This spring can then release its strain by altering the
      protein environment.

PMID- 15563130
TI  - High-resolution structure of an extended A-tract: [d(CGCAAATTTGCG)]2.
AB  - The crystal structure of [d(CGCAAATTTGCG)]2 has been determined to 1.5 A
      resolution, representing the first high-resolution structure of this DNA
      fragment. The ion interactions are novel. A spermine molecule replaces a Mg2+
      observed in analogous structures. Unlike lower-resolution structures, the minor
      groove is narrow and the major groove lacks extra Watson-Crick hydrogen bonds. In
      addition, a monolayer of solvent sites, including a "spine of hydration", is
      visible in the minor groove. The crystal of [d(CGCAAATTTGCG)]2 was grown from a
      solution containing spermine, magnesium, and lithium. The conformation
      recapitulates that of "monovalent-minus" DNA.

PMID- 15563131
TI  - Two CO molecules can bind concomitantly at the diiron site of NO reductase from
      Bacillus azotoformans.
AB  - CO complexes formed in reduced nitric oxide reductase from Bacillus azotoformans
      were investigated with resonance Raman and FTIR techniques. These experiments
      shows the presence of two nu(C-O) bands, one at approximately 1970 cm-1 assigned
      to the heme-CO complex, and one at approximately 2070 cm-1 from the non-heme
      iron, FeBCO. At cryogenic temperatures, the heme-CO complex adopts a semi
      bridging configuration with FeB which decreases its stretching frequency to
      approximately 1910 cm-1 and decreases the nu(C-O) of FeBCO by approximately 20 cm
      1. The concomitant binding of two CO molecules, one per iron(II) at the active
      site, is consistent with the formation of a [{FeNO}7]2 iron-nitrosyl dimer during
      substrate turnover. This study strongly supports the notion that this family of
      enzymes utilizes a reaction mechanism based on catalysis by proximity, where the
      formation of two iron-nitrosyl groups promotes N-N bond formation.

PMID- 15563132
TI  - Regiospecific functionalization of methyl C-H bonds of alkyl groups in reagents
      with heteroatom functionality.
AB  - We report the regiospecific, rhodium-catalyzed borylation of saturated terminal C
      H bonds in molecules with existing functionality. Moderate to good yields were
      obtained with the organic substrate in excess and as limiting reagent. The
      borylations of trialkylamines, protected alcohols, protected ketones, and
      fluoroalkanes occurred regiospecifically at the methyl group that is least
      sterically hindered. Reactions were also conducted that probed electronic effects
      on the alkyl borylation. These reactions showed that the borylation occurred
      preferentially at the methyl group that is most electron-deficient. Methods to
      conduct tandem borylation of C-H bonds and conversion of the resulting boronate
      esters to alcohols, alkylarenes, and alkyltrifluoroborates were also developed.

PMID- 15563133
TI  - Direct aziridination of alkenes by a cationic (salen)ruthenium(VI) nitrido
      complex.
AB  - [RuVI(N)(salchda)(CH3OH)]PF6 (1) (salchda = N,N'-bis(salicylidene)o
      cyclohexyldiamine dianion) reacts readily with 2,3-dimethyl-2-butene at room
      temperature in the presence of pyridine or 1-methylimidazole to give initially
      [RuIV(Az1(-H))(salchda)(py)]PF6 (2, Az1 = 2,2,3,3-tetramethylaziridine), which is
      then slowly reduced to [RuIII(Az1)(salchda)(py)]PF6 (3). 1 also reacts with a
      variety of aryl-substituted alkenes such as styrene and trans-beta-methylstyrene
      in the presence of py or 1-MeIm to give the corresponding ruthenium(III)
      aziridine complexes. The structures of 3 and [RuIII(Az2)(salchda)(1-MeIm)]PF6 (4,
      Az2 = trans-2-methyl-3-phenylaziridine) have been determined by X-ray
      crystallography. The Ru-N(aziridine) distances (2.1049, 2.097 A) are consistent
      with a neutral aziridine ligand. The C-C and C-N distances in the aziridine
      ligands are all indicative of single bonds.

PMID- 15563134
TI  - Catalytic enantioselective hydrogenation of vinyl bis(boronates).
AB  - Catalytic enantioselective hydrogenation of prochiral vinylmetallic reagents can
      provide an attractive alternative to hydrometalation and bismetalation of
      alkenes. In this contribution, the first highly enantioselective hydrogenation of
      vinyl boronic esters is described. The chiral reduction products are versatile
      intermediates for chemical synthesis.

PMID- 15563135
TI  - High-resolution NMR spectroscopy of membrane proteins in aligned bicelles.
AB  - High-resolution solid-state NMR spectra can be obtained from uniformly (15)N
      labeled membrane proteins in magnetically aligned bicelles. Fast uniaxial
      diffusion about the axis of the bilayer normal results in single-line spectra
      that contain the orientational information necessary for protein structure
      determination.

PMID- 15563136
TI  - Ligand-switchable directing effects of tethered alkenes in nickel-catalyzed
      additions to alkynes.
AB  - Nickel-catalyzed reductive couplings of aldehydes with alkynes that contain
      tethered olefins are described, in which the degree and sense of regioselectivity
      are controlled by the length of the tether and the presence or absence of an
      additive. When the alkyne and alkene are separated by four bonds, very high
      (>95:5) regioselectivities are observed. Use of a monodentate phosphine as an
      additive leads to formation of the opposite regioisomer in equal and opposite
      selectivity (5: >95). These results provide strong evidence for an interaction
      between the remote alkene and the metal center during the regioselectivity
      determining step and suggest that reactions with and without an additive proceed
      via fundamentally distinct mechanisms.

PMID- 15563137
TI  - A quantitative assessment of the influence of permanent kinks on the mixing
      behavior of phospholipids in cholesterol-rich bilayers.
AB  - The mixing behavior of a phospholipid containing a cis-cyclopropyl moiety (1)
      with one that contains two myristoyl groups (3a) has been investigated in fluid
      bilayers via the nearest-neighbor recognition (NNR) method. In the absence of
      cholesterol, these lipids mix ideally. In the presence of cholesterol, they show
      a modest preference for homo-phospholipid association. A trans-form of 1 (i.e.,
      2) was found to have similar behavior, except that the influence of cholesterol
      in promoting homo-phospholipid association was greater. Similar results have been
      found in membranes in which 3a is replaced with a phospholipid bearing two
      palmitoyol chains (3b). In this case, the effect of the kink is approximately
      twice as great. The implications of these findings, with respect to the "trans
      fatty acid debate", are briefly discussed

PMID- 15563138
TI  - Total synthesis of (-)-disorazole C1.
AB  - The antimitotic natural product disorazole C1 was isolated in 1994 from the
      fermentation broth of the myxobacterium Sorangium cellulosum. We have developed a
      highly convergent and stereoselective total synthesis of this compound which
      establishes its relative and absolute configuration. Key features of our
      synthesis include a highly convergent strategy and selective functional group
      manipulations that minimize decomposition of the sensitive polyene macrodiolide.

PMID- 15563139
TI  - Spirodiepoxides in total synthesis: epoxomicin.
AB  - The first use of the spirodiepoxide functional group in total synthesis, a study
      culminating in an efficient synthesis of the potent proteasome inhibitor
      epoxomicin, is described. Spirodiepoxides derived from allenes by oxidation are
      shown to give syn disubstituted ketones and their derivatives, including ortho
      ester, oxazoline, azido epoxide, as well as sulfonamide-, amide-, and azide
      containing hydroxy ketones.

PMID- 15563140
TI  - Phosphoryl choline introduces dual activity in biomimetic ionomers.
AB  - Dual activity of phosphoryl choline (PC) functional poly(trimethylene carbonate)
      (PTMC) was found which induces the zwitterionic biomimetic PC group to form
      physical cross-links with ionomers in the bulk, and at the same time enrich at
      the surface of cast films. The formation of zwitterionic domains from a
      bifunctional PC-PTMC-PC (ionomer) provided firm films with a low elastic modulus
      in contrast to the tacky PTMC starting material (Mn approximately 3900 g/mol)
      with poor mechanical performance. In addition, the ionomer possessed improved
      hemocompatible properties that was explained by the enrichment of PC at the
      surface, suggesting a way to tailor the mechanical performance of biodegradable
      PTMC-based ionomers while providing its bioactivity. Tailored elasticity while
      maintaining hemocompatibility of a biodegradable ionomer should be of particular
      interest for a variety of in vivo applications.

PMID- 15563141
TI  - Understanding strong two-photon absorption in pi-conjugated porphyrin dimers via
      double-resonance enhancement in a three-level model.
AB  - We present the two-photon absorption (2PA) spectra of a series of conjugated
      porphyrin dimers and show that they possess extremely large intrinsic
      (femtosecond) peak 2PA cross sections, up to sigma2 = 1 x 104 GM in the near-IR
      region; these are among the highest values measured for any organic molecule.
      Moreover, we demonstrate that the second-order perturbation theory applied to a
      simple three-level model gives a perfect quantitative description of the observed
      2PA cross section. By comparing all the factors of the three-level model for
      dimers with those of corresponding monomer (for which sigma2 = 20 GM), we explain
      an approximately 500-fold cooperative enhancement in sigma2 and find that the
      most important factor is the strength of excited-state transition. The matrix
      element of dipole moment of this transition amounts gigantic values of 30-40 D
      for conjugated porphyrin dimers, which can be accounted for a large
      delocalization radius (large electron-hole separation) in this state. We also
      demonstrate efficient generation of singlet oxygen upon one- and two-photon
      excitation of these porphyrin dimers, which can be useful for two-photon
      initiated photodynamic therapy of cancer.

PMID- 15563142
TI  - Palladium-catalyzed carbon-carbon bond-forming 1,2-ligand migration of
      organoalanes.
AB  - A one-pot, two-step process that transforms terminal alkynes into ethyl methyl
      substituted benzylic quaternary carbon centers is described. (E)-2,2
      Disubstituted-1-alkenyldimethylalanes have been shown to participate in 1,2-alkyl
      migration from aluminum to carbon with concomitant arylation at the 2-position to
      furnish ethyl methyl-substituted benzylic quaternary carbon centers, when reacted
      intramolecularly with aryl halides and triflates in the presence of a Pd(0)
      catalyst. The protocol is initiated with Cp2ZrCl2-catalyzed methylalumination of
      terminal alkynes followed by palladium-catalyzed intramolecular arylation of the
      resulting (E)-2,2-disubstituted-1-alkenyldimethylalanes, leading to 1,2-methyl
      shift from aluminum to carbon. In that sequence, a total of three new C-C single
      bonds are made, and two of the three alkyl groups on Me3Al transferred to the
      substrate on vicinal carbons. This method was applied to a variety of substrates,
      and the mechanism was investigated by deuterium-labeling experiments, which
      revealed that protodealumination of the final dialkylaluminum triflate or halide
      intermediates by CH3CN results in the formation of the fourth bond in the course
      of the transformation.

PMID- 15563143
TI  - Direct access to ketones from aldehydes via rhodium-catalyzed cross-coupling
      reaction with potassium trifluoro(organo)borates.
AB  - A direct cross-coupling reaction of aromatic aldehydes with potassium
      trifluoro(organo)borates afforded ketones in high yields and under mild
      conditions in the presence of a rhodium catalyst and acetone. This new reaction,
      involving a formal aldehyde C-H bond activation, is believed to proceed via a
      Heck-type mechanism followed by hydride transfer to acetone.

PMID- 15563144
TI  - A liquid derivative of 12-tungstophosphoric acid with unusually high
      conductivity.
AB  - Surface functionalization of the solid heteropolyacid H3PW12O40 with a bulky PEG
      containing quaternary ammonium cation through partial proton exchange leads to a
      polyoxometalate-based liquid salt with high-temperature proton conductivity (
      approximately 10-3 S cm-1 at 140 degrees C) under dry conditions. The proton
      conductivity of the liquid salt is 4 orders of magnitude higher than that of the
      solid analogue under identical conditions and shows super ionic behavior as
      defined by Walden plot.

PMID- 15563145
TI  - Structures and reactivity of Zr(IV) chlorobenzene complexes.
AB  - The synthesis, structures, and unusual reactivity of (C5R5)2ZrR'(ClPh)+
      chlorobenzene complexes are described. The reaction of (C5R5)2ZrR'2 with
      [Ph3C][B(C6F5)4] in C6D5Cl affords [(C5R5)2ZrR'(ClC6D5)][B(C6F5)4] chlorobenzene
      complexes (1-d5, R' = CH2Ph and (C5R5)2 = (C5H5)2; 2a-d-d5, R' = Me and (C5R5)2 =
      rac-(1,2-ethylene(bis)indenyl) (2a), (C5H5)2 (2b), (C5H4Me)2 (2c), (C5Me5)2 (2d,
      C5Me5 = Cp*)). Complexes 1 and 2b,c are thermally robust but are converted to
      [{(C5R5)2Zr(mu-Cl)}2][B(C6F5)4]2 (4b,c) by a photochemical process in ClPh
      solution. In contrast, 2d undergoes facile thermal ortho-C-H activation to yield
      [Cp*2Zr(eta2-C,Cl-2-Cl-C6H4)][B(C6F5)4] (5), which slowly rearranges to
      [(eta4,eta1-C5Me5C6H4)Cp*ZrCl][B(C6F5)4] (6) via beta-Cl elimination and benzyne
      insertion into a Zr-CCp* bond. The higher thermal reactivity of 2d versus that of
      1 and 2b,c is attributed to steric crowding associated with the Cp* ligands of
      2d, which forces a ClPh ortho-hydrogen close to the Zr-Me group.

PMID- 15563146
TI  - Dynamic in situ electrochemical neutron reflectivity measurements.
AB  - We report the first dynamic in situ electrochemical neutron reflectivity (NR)
      measurements on electroactive films. By using a boxcar integration strategy
      within a cyclic voltammetric experiment, it is possible to acquire neutron
      reflectivity data associated with narrow, defined windows of potential.
      Accumulation of data from repetitive cycles allows one to build up potential-
      (time-) resolved profiles. The effective time resolution is now on the order of
      seconds, as compared to ca. 1 h using conventional methodology, making in situ NR
      a practical technique for dynamic electrochemical studies. Illustrative data for
      polyvinylferrocene films reveal hysteresis in (de)swelling, incomplete
      desolvation upon reduction, and transient salt retention, all of which respond to
      time-scale variations.

PMID- 15563147
TI  - Anion-templated assembly of a [2]catenane.
AB  - The first example of a [2]catenane structure to be synthesized using anion
      templation is described. The nature of the anion template is demonstrated to be
      crucial to the assembly process, with only chloride anion producing the
      [2]catenane in acceptable yield. Anion binding studies reveal a dramatic
      catenation effect on anion selectivity properties as compared to a noncatenated
      acyclic receptor.

PMID- 15563148
TI  - Heterocyclic peptide backbone modifications in an alpha-helical coiled coil.
AB  - In this paper, we present 1,2,3-triazole epsilon2-amino acids incorporated as a
      dipeptide surrogate at three positions in the sequence of a known alpha-helical
      coiled coil. Biophysical characterization indicates that the modified peptides
      retain much of the helical structure of the parent sequence, and that the
      thermodynamic stability of the coiled coil depends on the position of the
      incorporation of the epsilon-residue. Crystal structures obtained for each
      peptide give insight into the chemical behavior and conformational preferences of
      the non-natural amino acid and show that the triazole ring can participate in the
      backbone hydrogen bonding of the alpha-helix as well as template an interhelical
      crossing between chains in the bundle.

PMID- 15563149
TI  - Protein patterning based on electrochemical activation of bioinactive surfaces
      with hydroquinone-caged biotin.
AB  - We report a protein attachment and patterning method based on a hydroquinone
      caged biotin surface that generates bioactive biotin by mild electrochemical
      perturbation. The electrochemical activation proceeds under the buffered aqueous
      environment at neutral pH. It also allows site-selective generation of bioactive
      biotin for the immobilization of target protein by using prepatterned electrode
      arrays.

PMID- 15563150
TI  - Chemistry and biology of deoxy-myo-inositol phosphates: stereospecificity of
      substrate interactions within an archaeal and a bacterial IMPase.
AB  - Six enantiomerically pure myo-inositol-monophosphates, including four
      deoxygenated analogues, have been synthesized by employing catalytic asymmetric
      phosphorylation methodology. These compounds were then evaluated as substrates
      for the direct interrogation of the stereospecificity of enzyme-substrate
      interactions with two inositol-monophosphatases (IMPases), one of which (from
      Archaeoglobus fulgidus) is characterized by an X-ray crystal structure with its
      substrate (d-I-1P) bound. The kinetic results lead to the finding that certain
      hydroxyl group contacts are actually destabilizing, while others have little
      effect. These new probes also allow a prediction of the active site binding mode
      of the substrate for the Escherichia coli IMPase for which no crystal structure
      exists.

PMID- 15563151
TI  - Cysteine-reactive polymers synthesized by atom transfer radical polymerization
      for conjugation to proteins.
AB  - In this communication we report a strategy for the synthesis of semitelechelic
      polymers reactive to cysteines. An initiator modified with a pyridyl disulfide
      was prepared and used for the CuBr/2,2'-bipyridine-mediated atom transfer radical
      polymerization (ATRP) of 2-hydroxyethyl methacrylate. Polydispersity indices
      (M(w)/M(n)) of the polymers with different molecular weights were 1.25 or less.
      The pyridyl disulfide end group was preserved during the polymerization and
      allowed direct conjugation of the polymer to cysteine residues of bovine serum
      albumin. The described method provides a general way for the preparation of
      protein-polymer conjugates through a reversible disulfide bond without the need
      for postsynthesis modification of the polymers.

PMID- 15563152
TI  - Sequence-selective and hydrolytic cleavage of DNA by zinc finger mutants.
AB  - We have reported the successful conversion of the structural zinc site in zinc
      finger peptides to a functional zinc site. A series of resulting zinc finger
      mutants exhibit the hydrolytic ability of the activated ester depending on the
      coordination geometry and acidity of the zinc ions. In this study, we explored
      the hydrolytic ability of DNA by the H4 mutant since the mutant showed the
      highest hydrolytic ability of the activated ester among the series of mutant
      peptides. The zinc-bound form of the H4 mutant peptide exhibited the hydrolytic
      ability of activated phosphoesters and even converted the supercoiled plasmid to
      the nicked circular form. An increasing ionic strength leads to a loss in the
      nuclease ability of the zinc finger mutants due to the nonspecific interaction
      between the zinc finger peptide and DNA. In sharp contrast, the three-tandem H4
      type zinc finger protein performed the specific DNA hydrolysis at the GC box even
      at a high ionic strength. Thus, the present study demonstrated that converting
      the native zinc site to the hydrolytic zinc site in the zinc finger protein is a
      novel approach for creating artificial nucleases with sequence selectivity.

PMID- 15563153
TI  - Specific redistribution of cell-penetrating peptides from endosomes to the
      cytoplasm and nucleus upon laser illumination.
AB  - Cell-penetrating peptides (CPPs), once postulated to cross cell membranes in a
      non-endocytic, non-energy-dependent process, have since been found to accumulate
      in vesicles in live mammalian cells. In this study, we show that it is possible
      to use laser light from a confocal microscope to cause labeled peptide-conjugated
      CPPs to redistribute from vesicles into the cytoplasm and nucleus of cells.
      Following redistribution, the cells are found to be biologically responsive, and
      they retain morphology for several hours. It was possible to initiate
      redistribution of both fluorescein- and Alexa633-labeled peptides by selective
      irradiation of one of the fluorophores. These peptides could potentially be used
      as tracers to selectively deliver cargo biomolecules into cells by laser
      illumination using a standard fluorescence confocal microscope.

PMID- 15563154
TI  - Expanding the scope of C-H amination through catalyst design.
AB  - Analysis of the mechanism for Rh-mediated C-H amination has led to the
      development of a remarkably effective dinuclear Rh catalyst derived from 1,3
      benzenedipropionic acid. This unique complex, Rh2(esp)2, is capable of promoting
      both intra- and intermolecular C-H oxidation reactions, and in all cases is
      superior to Rh2(O2CtBu)4. For the first time, C-H insertion is described with
      urea and sulfamide substrates to give 1,2- and 1,3-diamine derivatives,
      respectively. In addition, intermolecular amination of benzylic and secondary C-H
      bonds is shown to proceed efficiently even under conditions in which the starting
      alkane is employed as the limiting reagent.

PMID- 15563155
TI  - Comparative study of electron transfer reactions at the ionic liquid/water and
      organic/water interfaces.
AB  - The rates of electron transfer (ET) reactions at the water/ionic liquid (IL)
      interface have been measured for the first time using scanning electrochemical
      microscopy. The standard bimolecular rate constant of the interfacial ET between
      ferrocene dissolved in 1-octyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide and aqueous ferricyanide (0.4 M-1 cm s-1) was
      found to be approximately 30 times higher than the corresponding rate constant
      measured at the water/1,2-dichloroethane interface. The driving force dependence
      of the ET rate was investigated over a wide range of the interfacial potential
      drop values (>200 mV). The observed Butler-Volmer-type dependence is discussed in
      terms of the interfacial model. The ET was also probed at the interface between
      aqueous solution and the mixture of the IL and 1,2-dichloroethane. The mole
      fractions in this mixture were varied systematically to investigate the
      transition from the water/organic to the water/IL interface. The observed
      decrease in the rate constant with increasing mole fraction of 1,2-dichloroethane
      is in contrast with the previously reported direct correlation between the
      electrochemical rate constant and the diffusion coefficient of redox species in
      solution.

PMID- 15563156
TI  - Design of mesomorphic diarylethene-based photochromes.
AB  - The effects of the molecular variation of diarylethenes on the mesomorphic,
      photochromic, and fluorescence properties have been investigated, and dramatic
      changes in the fluorescence, photochromic, and liquid crystal behavior were
      observed.

PMID- 15563157
TI  - Vinyl acetate formation by the reaction of ethylene with acetate species on
      oxygen-covered Pd(111).
AB  - The reaction pathway of vinyl acetate synthesis is scrutinized by reacting gas
      phase ethylene (at an effective pressure of 1 x 10-4 Torr) with eta2-acetate
      species (with a coverage of 0.31 +/- 0.02 monolayer) on a Pd(111)-O(2x2) model
      catalyst surface in ultrahigh vacuum. It is found that the 1414 cm-1 infrared
      feature due to the symmetric OCO stretching mode of the acetate species decreases
      in intensity due to reaction with gas-phase ethylene, while temperature
      programmed desorption experiments demonstrate that vinyl acetate is formed. The
      formation of ethylidyne species is detected when almost all of the acetate
      species have been removed. The experimental removal kinetics are reproduced by a
      model in which adsorbed acetates react with an ethylene-derived (possibly
      ethylene or vinyl) species, where ethylene adsorption is blocked by the acetate
      present on the surface.

PMID- 15563158
TI  - Understanding the basis of resistance in the irksome Lys103Asn HIV-1 reverse
      transcriptase mutant through targeted molecular dynamics simulations.
AB  - Results of targeted molecular dynamics simulations confirm the existence of a
      higher energy barrier for creation of the pocket where non-nucleoside reverse
      transcriptase inhibitors bind in the K103N mutant enzyme relative to wild-type.

PMID- 15563159
TI  - Platinum-functionalized random copolymers for use in solution-processible,
      efficient, near-white organic light-emitting diodes.
AB  - A near-white light-emitting polymer, consisting of hole transport (HT), electron
      transport (ET), and phosphorescent Pt functionalities, was prepared and utilized
      as the emissive layer in solution-processed OLEDs. The air-stable devices had a
      maximum external quantum efficiency of 4.6%.

PMID- 15563160
TI  - Zero thermal expansion in a Prussian Blue analogue.
AB  - Isotropic nearly zero thermal expansion (i.e., negligible volume change) is
      reported in a large temperature range for Fe[Co(CN)6], a member of the Prussian
      blue family with electronically active metal sublattices and a cubic framework
      structure built by a cyanide-bridged network of octahedral units. Suitable
      selection of metal ions and interstitial units could allow such anomalous thermal
      behavior to be combined with the variety of unusual electronic, optical, and
      magnetic properties exhibited by Prussian blue analogues.

PMID- 15563161
TI  - A selective, cell-permeable optical probe for hydrogen peroxide in living cells.
AB  - We present the synthesis, properties, and biological applications of Peroxyfluor
      1 (PF1), a new type of optical probe for intracellular imaging of hydrogen
      peroxide in living biological samples. PF1 utilizes a boronate deprotection
      mechanism to provide unprecedented selectivity and optical dynamic range for
      detecting H2O2 in aqueous solution over similar reactive oxygen species including
      superoxide, nitric oxide, tert-butyl hydroperoxide, and hydroxyl radical. We
      further demonstrate the value of this reagent for biological applications by
      imaging changes in [H2O2] in living mammalian cells.

PMID- 15563162
TI  - Coordination polymers containing 1D channels as selective luminescent probes.
AB  - Two 3d-4f heterometallic coordination polymers
      {[Ln(PDA)3Mn1.5(H2O)3].3.25H2O}infinity with 1D channels were synthesized under
      hydrothermal conditions (PDA = pyridine-2,6-dicarboxylic acid; Ln = Eu (1); Ln =
      Tb (2)). The emission intensities of 1 and 2 increased significantly upon
      addition of Zn2+, while the introduction of other metal ions caused the intensity
      to be either unchanged or weakened. The case implies that 1 and 2 may be used as
      luminescent probes of Zn2+.

PMID- 15563163
TI  - Pyrimidine-core extended pi-systems: general synthesis and interesting
      fluorescent properties.
AB  - We have developed a simple but powerful synthetic strategy that permits the
      assembly of pi-systems onto a pyrimidine core in a programmable and diversity
      oriented format. The nucleophilic addition of ArLi to 2-methylthiopyrimidine,
      followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation, resulted
      in the production of 4-aryl-2-methylthiopyrimidines. The iterative reaction
      sequence then gave 4,6-diaryl-2-methylthiopyrimidines. The resulting adduct was
      further allowed to react with ArMgBr under the catalytic influence of NiCl2(dppe)
      to afford 2,4,6-triarylpyrimidines. By following this synthetic scheme,
      interesting pyrimidine-core pi-systems were rapidly constructed in a programmable
      fashion. The successful discovery of a number of interesting fluorescent
      materials and properties (e.g., solvatofluorochromism) speaks well for the
      potential of our platform strategy in the development of functional organic
      materials.

PMID- 15563164
TI  - Induction of homochirality in achiral enantiomorphous monolayers.
AB  - We report the induction of homochirality in enantiomorphous layers of achiral
      succinic acid on a Cu(110) surface after doping with tartaric acid (TA)
      enantiomers. Succinic acid becomes chiral upon adsorption due to symmetry
      breaking interactions with the Cu(110) surface. The doubly deprotonated
      bisuccinate forms mirror domains on the surface, which leads to a superposition
      of (11,-90) and (90,-11) patterns observed by low-energy electron diffraction
      (LEED). On average, however, the surface layer is racemic. An amount of 2 mol %
      of (R,R)- or (S,S)-tartaric acid in the monolayer, corresponding to an absolute
      coverage of 0.001 tartaric acid molecule per surface copper atom, is sufficient
      to make the LEED spots of one enantiomorphous lattice disappear. After thermally
      induced desorption of TA, the succinic acid lattice turns racemic again. In
      analogy to the "sergeants-and-soldiers" principle described for helical polymers,
      this effect is explained by a lateral cooperative interaction within the two
      dimensional lattice.

PMID- 15563165
TI  - Chemical input multiplicity facilitates arithmetical processing.
AB  - We describe the design and function of a molecular logic system, by which a
      combinatorial recognition of the input signals is utilized to efficiently process
      chemically encoded information. Each chemical input can target simultaneously
      multiple domains on the same molecular platform, resulting in a unique
      combination of chemical states, each with its characteristic fluorescence output.
      Simple alteration of the input reagents changes the emitted logic pattern and
      enables it to perform different algebraic operations between two bits, solely in
      the fluorescence mode. This system exhibits parallelism in both its chemical
      inputs and light outputs.

PMID- 15563166
TI  - Combating drug-resistant bacteria: small molecule mimics of plasmid
      incompatibility as antiplasmid compounds.
AB  - A major mechanism for bacterial resistance to antibiotics is through the
      acquisition of a plasmid coding for resistance-mediating proteins. Described
      herein is a strategy to eliminate these plasmids from bacteria, thus
      resensitizing the bacteria to antibiotics. This approach involves mimicking a
      natural mechanism for plasmid elimination, known as plasmid incompatibility. The
      compound apramycin was identified as a tight binder to SLI RNA (Kd = 93 nM), the
      in vivo target of the plasmid incompatibility determinate RNA I, and
      footprinting/mutagenesis studies indicate apramycin binds SLI in the important
      regulatory region that dictates plasmid replication control and incompatibility.
      In vivo studies demonstrate that this compound causes significant plasmid loss
      and resensitizes bacteria to conventional antibiotics. The demonstration that a
      small molecule can mimic incompatibility, cause plasmid elimination, and
      resensitize bacteria to antibiotics opens up new targets for antibacterial
      research.

PMID- 15563167
TI  - The complex of a bivalent derivative of galanthamine with torpedo
      acetylcholinesterase displays drastic deformation of the active-site gorge:
      implications for structure-based drug design.
AB  - Bifunctional derivatives of the alkaloid galanthamine, designed to interact with
      both the active site of the enzyme acetylcholinesterase (AChE) and its peripheral
      cation binding site, have been assayed with Torpedo californica AChE (TcAChE),
      and the three-dimensional structures of their complexes with the enzyme have been
      solved by X-ray crystallography. Differences were noted between the IC(50) values
      obtained for TcAChE and those for Electrophorus electricus AChE. These
      differences are ascribed to sequence differences in one or two residues lining
      the active-site gorge of the enzyme. The binding of one of the inhibitors
      disrupts the native conformation of one wall of the gorge, formed by the loop
      Trp279-Phe290. It is proposed that flexibility of this loop may permit the
      binding of inhibitors such as galanthamine, which are too bulky to penetrate the
      narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal
      structure.

PMID- 15563168
TI  - A general and high yielding fragment coupling synthesis of heteroatom-bridged
      calixarenes and the unprecedented examples of calixarene cavity fine-tuned by
      bridging heteroatoms.
AB  - A number of aza- and/or oxo-bridged calix[2]arene[2]triazines have been
      synthesized through an unusually high yielding and efficient fragment coupling
      approach starting from cyanuric chloride and resorcinol, 3-aminophenol, m
      phenylenediamine, and N,N'-dimethyl-m-phenylenediamine. These novel macrocycles,
      which belong to the next generation of calixarenes or cyclophanes, form a unique
      cavity that is resulted from two isolated benzene planes and two bis-heteroatom
      conjugated triazine planes in a 1,3-alternate fashion. The nature of the bridging
      heteroatoms, i.e., combination of the electronic, conjugative, and steric effects
      of the nitrogen and oxygen atoms, strongly regulates the cavity size, generating
      a set of fine-tuned cavities in which the distance between two benzene rings at
      the upper rim ranges from 5.011 to 7.979 A. The multiple intermolecular hydrogen
      bond interactions among N,N'-dimethylated tetraazacalix[2]arene[2]triazines and
      among tetraazacalix[2]arene[2]triazines lead to the formation of infinite one
      dimensional chain structure and two-dimensional zigzag layered structure,
      respectively, in the solid state. The ease of preparation and further chemical
      manipulations, and the readily tunable cavity structures render these aza- and/or
      oxo-bridged calix[2]arene[2]triazines the unique platforms in the study of
      supramolecular chemistry.

PMID- 15563169
TI  - Catalytic cyclization of o-alkynylbenzaldehyde acetals and thioacetals.
      Unprecedented activation of the platinum catalyst by olefins. Scope and mechanism
      of the reaction.
AB  - A general protocol for the synthesis of functionalized indenes from o
      alkynylbenzaldehyde acetals and thioacetals has been elaborated. Acetals
      uniformly give cyclization products having the alkyl group from the starting
      acetylene migrated to the alpha-position, whereas the cyclization of the
      corresponding thioacetals proceeds without alkyl migration. Optimization of the
      catalytic system for the cyclization of o-alkynylbenzaldehyde acetals revealed an
      unknown activation effect: PtCl(2) was found to be a better catalyst for the
      cyclization of acetals in the presence of olefins than without. A similar
      catalytic system (PtCl(2)/benzoquinone) has been found to be appropriate for the
      cyclization of cyclic acetals, whereas the optimal catalyst for the reaction of
      thioacetals is PdI(2). NMR monitoring of two reactions, acetal 3a +
      Pd(CH(3)CN)Cl(2) in CD(3)CN and thioacetal 5j + PdI(2) in CD(2)Cl(2), revealed
      that in both reactions similar cationic species are formed at the early stage of
      the transformation. Computational data (B3LYP/SDD level of theory) suggest that
      the difference in the reaction pathways for acetals and thioacetals can be
      rationalized by taking into account the relative stabilities of the corresponding
      vinylpalladium intermediates (22 vs 20 and 19 vs 21), which suggests a reversible
      thermodynamically controlled alkyl migration in the intermediate vinylcationic
      species.

PMID- 15563170
TI  - Electron transfer within 2,7-dinitronaphthalene radical anion.
AB  - The optical spectrum of 2,7-dinitronaphthalene radical anion generated by Na(Hg)
      reduction in acetonitrile containing a large excess of cryptand[2.2.2] exhibits a
      Hush-type intervalence charge-transfer band at 1070 nm, estimated to correspond
      to an off-diagonal matrix coupling element of 310 cm(-)(1). The interpolated rate
      constant for intramolecular electron transfer at 293 K measured by ESR between
      225 and 320 K for this solution is 3.1(+/-0.2) x 10(9) s(-)(1). Rate constants
      estimated in two ways from the optical parameters using the Marcus-Hush
      assumption that the diabatic surfaces should be parabolae are 1.0 and 0.11 x
      10(9) s(-1), and those using diabatic surfaces that fit the observed charge
      transfer band are 9.6 and 3.4 x 10(9) s(-)(1), when used with an electron
      transfer distance on the adiabatic surfaces of 6.42 A. Similar measurements and
      comparisons were also carried out using dimethylformamide and butyronitrile as
      solvents. The success of simple, classical two-state Marcus-Hush theory precludes
      an electron-hopping mechanism. UHF calculations predict a planar unsymmetrical
      gas-phase structure for 1,3-dinitrobenzene radical anion but give serious spin
      contamination. Semiempirical AM1 calculations using singles excitation
      configuration interaction with an active space of 70 orbitals and the COSMO
      solvent model also give a planar unsymmetrical structure. These calculations make
      the internal vibrational component of the reorganization energy nearly constant,
      and much smaller than the solvent reorganizational component, and predict the
      transition energy to lie between that observed in acetonitrile (9360 cm(-1)) and
      those observed in dimethylformamide (8100 cm(-1)) and butyronitrile (8040 cm(
      1)).

PMID- 15563171
TI  - Size-dependent exciton chirality in (R)-(+)-1,1'-bi-2-naphthol dimethyl ether
      nanoparticles.
AB  - Organic nanoparticles from a chiral auxiliary, (R)-(+)-1,1'-bi-2-naphthol
      dimethyl ether (BNDE), with a range of particle sizes from 25 to 100 nm were
      fabricated through the reprecipitation method. It is found that BNDE
      nanoparticles exhibit positive exciton chirality in 200-260 nm region in circular
      dichroism (CD) spectra, which are completely opposite to CD spectra of the dilute
      solution. The exciton chirality of the particles displays size-dependent
      behavior; that is, the exciton chirality peaks evolve to the low-energy side with
      increase in particles size. CD spectra accompanied with UV, fluorescence spectra,
      lifetime measurements of the excited states, and quantum mechanical calculations
      reveal that the chirality inversion results from intermolecular exciton coupling
      between two adjacent BNDE molecules in the nanoparticles, and the bathochromic
      shift of the peaks is attributed to the increased intermolecular interaction with
      increasing particle size.

PMID- 15563172
TI  - A family of manganese rods: syntheses, structures, and magnetic properties.
AB  - The reaction of the mixed-valent metal triangles [Mn(3)O(O(2)CR)(6)(py)(3)] (R =
      CH(3), Ph, C(CH(3))(3)) with the tripodal ligands H(3)thme (1,1,1
      tris(hydroxymethyl)ethane) and H(3)tmp (1,1,1-tris(hydroxymethyl)propane) in
      MeCN, produces a family of manganese rodlike complexes whose structures are all
      derived from a series of edge-sharing triangles. Variable temperature direct
      current (dc) magnetic susceptibility data were collected for all complexes in the
      1.8-300 K temperature range in fields up to 7.0 T. Complex 1,
      [Mn(12)O(4)(OH)(2)(PhCOO)(12)(thme)(4)(py)(2)], has an S = 7 ground state with
      the parameters g = 1.98 and D = -0.13 K. Complex 2,
      [Mn(8)O(4)((CH(3))(3)CCO(2))(10)(thme)(2)(py)(2)] has a ground state of S = 6,
      with g = 1.81 and D = -0.36 K. Complex 3,
      [Mn(7)O(2)(PhCO(2))(9)(thme)(2)(py)(3)], has a spin ground states of S = 7 with
      the parameters g = 1.78 and D = -0.20 K. The best fit for complex 4,
      [Mn(6)((CH(3))(3)CCO(2))(8)(tmp)(2)(py)(2)], gave a spin ground state of S = 3
      with the parameters g = 1.73 and D = -0.75 K, but was of poorer quality than that
      normally obtained. The presence of multiple Mn(2+) ions in the structure of 4
      leads to the presence of low-lying excited states with energy levels very close
      to the ground state, and in the case of complex 5,
      [Mn(6)(CH(3)CO(2))(6)(thme)(2)(H(2)tea)(2)], no satisfactory fit of the data was
      obtained. DFT calculations on 4 and 5 indicate complexes with spin ground states
      of S = 4 and S = 0 respectively, despite their topological similarities. Single
      crystal hysteresis loop and relaxation measurements show complex 1 to be a SMM.

PMID- 15563173
TI  - Effects of methyl substitution on radiative and solvent quenching rate constants
      of [Ru(phen)2dppz]2+ in polyol solvents and bound to DNA.
AB  - Methyl substituents on the distant benzene ring of the dppz ligand in the "light
      switch" complex [Ru(phen)(2)dppz](2+) have profound effects on the photophysics
      of the complexes in water as well as in the polyol solvents ethylene glycol,
      glycerol, and 1,2- and 1,3-propanediol. Whereas 11,12-dimethyl substitution
      decreases the rate of quenching by diminishing hydrogen bonding by solvent, the
      10-methyl substituent in addition also decreases both the radiative and the
      nonradiative rate constant for decay to the ground state of the non-hydrogen
      bonded excited state species. For both the 10-methyl and the 11,12-dimethyl
      derivatives, the effect of methyl substitution on the equilibrium of solvent
      hydrogen bonding to the excited state is due to changes in the entropy terms,
      rather than in the enthalpy, indicating that the effect is a steric perturbation
      of the solvent cage around the molecule. When intercalated into DNA, the effects
      of methyl substitution is smaller than those in polyol solvent or water,
      suggesting that the water molecules that quench the excited state by hydrogen
      bonding to the phenazine aza nitrogens mainly access them from the same groove as
      in which the Ru(II) ion resides. Since the Delta-enantiomer of [Ru(phen)(2)10
      methyl-dppz](2+) has an absolute quantum yield of up to 0.23 when bound to DNA, a
      value 7000 times higher than in pure water solution, it is promising as a new
      luminescent DNA probe.

PMID- 15563174
TI  - Chemical surface passivation of Ge nanowires.
AB  - Surface oxidation and chemical passivation of single-crystal Ge nanowires with
      diameters ranging between 7 and 25 nm were studied. The surface chemistry differs
      significantly from that of well-studied monolithic atomically smooth single
      crystal substrates. High-resolution Ge 3d XPS measurements reveal that Ge
      nanowires with chemically untreated surfaces exhibit greater susceptibility to
      oxidation than monolithic Ge substrates. Multiple solution-phase routes to Ge
      nanowire surface passivation were studied, including sulfidation, hydride and
      chloride termination, and organic monolayer passivation. Etching in HCl results
      in chloride-terminated surfaces, whereas HF etching leads to hydride termination
      with limited stability. Exposure to aqueous ammonium sulfide solutions leads to a
      thick glassy germanium sulfide layer. Thermally initiated hydrogermylation
      reactions with alkenes produce chemically stable, covalently bonded organic
      monolayer coatings that enable ohmic electrical contacts to be made to the
      nanowires.

PMID- 15563175
TI  - Is the A-ring of sparteine essential for high enantioselectivity in the
      asymmetric lithiation-substitution of N-Boc-pyrrolidine?
AB  - The simplest chiral portion of sparteine, N,N'-dimethyl-2-endo-methylbispidine,
      was prepared and evaluated in the asymmetric lithiation-substitution of N-Boc
      pyrrolidine. The results indicate that the complete A-ring of sparteine is
      essential for high levels of asymmetric induction. DFT-QSSR analyses of the
      diamine/Li(+) complexes and DFT calculations of the pertinent i-PrLi/diamine/N
      Boc-pyrrolidine complexes are predictive and provide complementary pictures of
      the stereochemical features critical to this transformation.

PMID- 15563176
TI  - An experimental and computational study of the enantioselective lithiation of N
      Boc-pyrrolidine using sparteine-like chiral diamines.
AB  - The enantioselective lithiation of N-Boc-pyrrolidine using sec-butyllithium and
      isopropyllithium in the presence of sparteine-like diamines has been studied
      experimentally and computationally at various theoretical levels through to
      B3P86/6-31G*. Of the (-)-cytisine-derived diamines (N-Me, N-Et, N-(n)Bu, N
      CH(2)(t)Bu, N-(i)Pr) studied experimentally, the highest enantioselectivity (er
      95:5) was observed with the least sterically hindered N-Me-substituted diamine,
      leading to preferential removal of the pro-R proton i.e., opposite
      enantioselectivity to (-)-sparteine. The experimental result with the N-Me
      substituted diamine correlated well with the computational results: at the
      B3P86/6-31G* level, the sense of induction was correctly predicted; the lowest
      energy complex of isopropyllithium/diamine/N-Boc-pyrrolidine also had the lowest
      activation energy (DeltaH++ = 11.1 kcal/mol, DeltaG++= 11.5 kcal/mol) for proton
      transfer. The computational results with the N-(i)Pr-substituted diamine
      identified a transition state for proton transfer with activation energies of
      DeltaH++= 11.7 kcal/mol and DeltaG++= 11.8 kcal/mol (at the B3P86/6-31G* level).
      Although comparable to (-)-sparteine and the N-Me-substituted diamine, these
      DeltaH++ and DeltaG++ values are at odds with the experimental observation that
      use of the N-(i)Pr-substituted diamine gave no product. It is suggested that
      steric crowding inhibits formation of the prelithiation complex rather than
      increasing the activation enthalpy for proton transfer in the transition state.
      Three other ligands (N-H and O-substituted as well as a five-membered ring
      analogue) were studied solely using computational methods, and the results
      predict that the observed enantioselectivity would be modest at best.

PMID- 15563177
TI  - Solution redox chemistry of carbon nanotubes.
AB  - UV/vis/NIR absorbance spectra were used to monitor electron transfer between
      small-molecule redox reagents and carbon nanotubes (CNTs). The oxidation of (6,
      5)-enriched nanotubes in water with K(2)Ir(Cl)(6) reveals a valence electron
      density of 0.2-0.4 e(-)/100 carbon atoms and a reduction potential of
      approximately 800 mV versus NHE. The reduction potential of CNTs is found to
      increase with increasing band gap and to decrease with the introduction of an
      anionic dispersant. In light of this newly revealed redox chemistry of CNTs, we
      propose that the previously observed bleaching of the CNT absorbance spectrum at
      low pH is most likely a consequence of the oxidation of the nanotubes by oxygen.
      These results demonstrate facile oxidation and reduction of CNTs, provide a way
      to quantify the population of valence electrons, and point to possible
      applications of CNT in the catalysis of redox reactions.

PMID- 15563178
TI  - A general technique to rank protein-ligand binding affinities and determine
      allosteric versus direct binding site competition in compound mixtures.
AB  - To realize the full potential of combinatorial chemistry-based drug discovery,
      generic and efficient tools must be developed that apply the strengths of
      diversity-oriented chemical synthesis to the identification and optimization of
      lead compounds for disease-associated protein targets. We report an affinity
      selection-mass spectrometry (AS-MS) method for protein-ligand affinity ranking
      and the classification of ligands by binding site. The method incorporates the
      following steps: (1) an affinity selection stage, where protein-binding compounds
      are selected from pools of ligands in the presence of varying concentrations of a
      competitor ligand, (2) a first chromatography stage to separate unbound ligands
      from protein-ligand complexes, and (3) a second chromatography stage to
      dissociate the ligands from the complexes for identification and quantification
      by MS. The ability of the competitor ligand to displace a target-bound library
      member, as measured by MS, reveals the binding site classification and affinity
      ranking of the mixture components. The technique requires no radiolabel
      incorporation or direct biochemical assay, no modification or immobilization of
      the compounds or target protein, and all reaction components, including any
      buffers or cofactors required for protein stability, are free in solution. We
      demonstrate the method for several compounds of wide structural variety against
      representatives of the most important protein classes in contemporary drug
      discovery, including novel ATP-competitive and allosteric inhibitors of the Akt-1
      (PKB) and Zap-70 kinases, and previously undisclosed antagonists of the M(2)
      muscarinic acetylcholine receptor, a G-protein coupled receptor (GPCR). The
      theoretical basis of the technique is analyzed mathematically, allowing
      quantitative estimation of binding affinities and, in the case of allosteric
      interaction, absolute determination of binding cooperativity. The method is
      readily applicable to high-throughput screening hit triage, combinatorial library
      based affinity optimization, and developing structure-activity relationships
      among multiple ligands to a given receptor.

PMID- 15563179
TI  - NMR-based reappraisal of the coordination of a metal ion at the pro-Rp oxygen of
      the A9/G10.1 site in a hammerhead ribozyme.
AB  - In the identification of a metal-binding site within enzymes, kinetic analyses
      based on thio-effects and Cd(2+)-rescues are widely used. In those analyses,
      kinetic studies using a phosphorothioate have been discussed on the premise that
      the substitution by a sulfur atom does not change the conformation of a ribozyme.
      However, our present NMR structural analysis demonstrates the change of the
      conformation at the metal-binding site by Rp-sulfur but not by Sp-sulfur
      substitution and warns against incautious interpretations of thio-effects and
      rescue phenomena in kinetic studies using a phosphorothioate. Our analysis
      further demonstrates that, in solution, a Cd(2+) ion can interact with an Rp
      phosphorothioate (in support of the controversial McKay's structure, Nature 1994,
      372, 68-74) and with an Sp-phosphorothioate (in support of the controversial
      Scott's structure, Cell 1995, 81, 991-1002) at the metal-binding A9/G10.1 site
      and that, in the former case, the bound Cd(2+) ion can return the ribozyme to an
      active conformation and rescue its enzymatic activity.

PMID- 15563180
TI  - Dynamics of alkoxy-oligothiophene ground and excited states in nanochannels.
AB  - Two oligothiophenes, 4,4'-dipentoxy-2,2'-dithiophene and 4,4"-dipentoxy
      2,2':5',2":5",2' ''-tetrathiophene, have been included in the nanochannels of the
      autoassembling host TPP (tris-o-phenylenedioxycyclotriphosphazene). The effect of
      the confinement on the structure and properties of the two dyes, as
      conformational arrangements, dynamics, and photophysical behavior, was addressed
      by the combination of high spinning speed solid-state NMR and time-resolved EPR
      spectroscopy. We compared the conformations of the dyes in their ground and
      photoexcited triplet states and described in detail the dynamics of the
      supramolecular adducts from 4 K to room temperature. Above 200 K surprisingly
      fast spinning rates of the dithiophene core were discovered, while the side
      chains show far slower reorientation motion, being in bulky gauche-rich
      conformations. These lateral plugs keep the planar core as appended in the space
      like a nanoscale gyroscope, allowing a reorientation in the motion regime of
      liquids and a long triplet lifetime at unusually high temperature. The nuclear
      magnetic properties of the guest dyes are also largely affected by the aromatic
      rings of the neighboring host, imparting an impressive magnetic susceptibility
      effect (2 ppm proton shift). The high mobility is due to the formation of a
      nanocage in a channel where aliphatic and aromatic functions isolate the
      thiophene moieties. Instead, two conformers of the tetrathiophene twisted on the
      central bond are stabilized by interaction with the host. They interconvert fast
      enough to be averaged in the NMR time scale.

PMID- 15563181
TI  - Electromechanics of a redox-active rotaxane in a monolayer assembly on an
      electrode.
AB  - A rotaxane monolayer consisting of the cyclophane, cyclobis(paraquat-p-phenylene)
      (2), threaded on a "molecular string" that includes a pi-donor diiminobenzene
      unit and stoppered by an adamantane unit is assembled on a Au electrode. The
      surface coverage of the electroactive cyclophane unit, E degrees = -0.43 V vs
      SCE, corresponds to 0.8 x 10(-10) mol.cm(-2). The cyclophane (2) is structurally
      localized on the molecular string by generating a pi-donor-acceptor complex with
      the diiminobenzene units of the molecular string. The cyclophane (2) acts as a
      molecular shuttle, revealing electrochemically driven mechanical translocations
      along the molecular wire. Reduction of the cyclophane (2) to the respective
      biradical-dication results in its dissociation from the pi-donor site, and the
      reduced cyclophane is translocated toward the electrode. Oxidation of the reduced
      cyclophane reorganizes 2 on the pi-donor-diiminobenzene sites. The positions of
      the oxidized and reduced cyclophane units are characterized by chronoamperometric
      and impedance measurements. Using double-step chronoamperometric measurements the
      dynamics of the translocation of the cyclophane units on the molecular string is
      characterized. The reduced cyclophane moves toward the electrode with a rate
      constant corresponding to k(1) = 320 s(-1), whereas the translocation of the
      oxidized cyclophane from the electrode to the pi-donor binding site proceeds with
      a rate constant of k(2) = 80 s(-1). Also, in situ electrochemical/contact angle
      measurements reveal that the electrochemically driven translocation of the
      cyclophane on the molecular string provides a means to reversibly control the
      hydrophilic and hydrophobic properties of the surface. The latter system
      demonstrates the translation of a molecular motion into the macroscopic motion of
      a water droplet.

PMID- 15563182
TI  - Conformationally locked isostere of phosphoSer-cis-Pro inhibits Pin1 23-fold
      better than phosphoSer-trans-Pro isostere.
AB  - Stereoisomeric cis and trans substrate analogues for Pin1 were designed and
      synthesized. The central phosphoSer-Pro core of the Pin1 substrate was replaced
      by cis and trans amide isosteres in Ac-Phe-Phe-pSer-Psi[(Z and E)CH=C]-Pro-Arg
      NH(2), 1 and 2, peptidomimetics. They were synthesized on solid phase in 17%
      yield for the cis analogue 1, and 16% yield for the trans analogue 2. A second
      trans amide isostere with a C-terminal N-methylamide 3 was synthesized in 7%
      yield. The protease-coupled Pin1 assay showed that all three compounds inhibited
      the Pin1 peptidyl-prolyl isomerase (PPIase) enzymatic activity. The cis isostere
      1 was 23 times more potent (K(i) = 1.74 +/- 0.08 muM) than its trans counterpart
      2 (K(i) = 40 +/- 2 muM) in competitive inhibition of Pin1. These results suggest
      that the catalytic site of Pin1 binds cis substrates more tightly in aqueous
      solution. Antiproliferative activity toward the A2780 human ovarian cancer cell
      line by the cis and trans analogues correlates with Pin1 inhibition results.

PMID- 15563183
TI  - Michael addition reactions with eta2-coordinated anisoles: controlling the
      stereochemistry of the para and benzylic carbons.
AB  - Several eta(2)-coordinated anisole complexes were treated with various Michael
      acceptors in the presence of a Lewis or Bronsted acid to generate stable 4H
      anisolium complexes. These reactions were found to proceed with high
      stereochemical control with predictable outcomes, provided that the moderate acid
      (NH(2)Ph(2))OTf was used and the complex was dissolved in an acidic solution. The
      stereochemistry is shown to originate from an unexpectedly high preference for
      one coordination diastereomer of the anisole complex in the solid state and a
      Diels-Alder like transition state for the Michael reaction.

PMID- 15563184
TI  - Reductive electron injection into duplex DNA by aromatic amines.
AB  - An assay based on photoinduced reaction and subsequent cleavage of duplex DNA
      containing a bromodeoxyuridine ((Br)U) residue and an abasic site was developed
      to screen aromatic amines for their ability to initiate charge transfer by
      reductive electron donation. Two candidates, N,N,N',N'-tetramethyl-1,5
      diaminonaphthalene (TMDN) and 1,5-diaminonaphthalene (DAN), expressed the desired
      activity, and an oligodeoxynucleotide-TMDN conjugate was subsequently prepared to
      identify additional variables affecting the efficiency of electron injection and
      transfer into DNA. This system demonstrated only mild sensitivity to molecular
      oxygen but was strongly inhibited by high concentrations of 2-mercaptoethanol.
      The nucleobase counter to the attached TMDN strongly modulated charge transfer as
      evident by a 60-fold decrease in reduction of the distal (Br)U when the
      counterbase A was substituted for C. An inverse relationship between this
      reduction and quenching of TMDN fluorescence by the counterbase was also
      discovered and is consistent with a competition between radical recombination and
      electron migration away from the initial site of its injection into DNA.

PMID- 15563185
TI  - Rutheniun-catalyzed cycloisomerization of o-(ethynyl)phenylalkenes to diene
      derivatives via skeletal rearrangement.
AB  - Treatment of a series of 2',2'-disubstituted (o-ethynyl)styrenes with
      TpRu(PPh(3))(CH(3)CN)(2)PF(6) (10 mol %) in benzene (80 degrees C, 12-18 h)
      efficiently gave 2-alkenyl-1H-indene derivatives. This catalytic reaction
      represents an atypical enyne cycloisomerization with skeletal rearrangement of
      starting enyne, where the C=C bond is completely cleaved and inserted by the
      terminal alkynyl carbon. The reaction mechanism was elucidated by a series of
      deuterium and (13)C labeling experiments, as well as by changing the substituents
      at the phenyl moieties. The mechanism is proposed to involve the following key
      steps: 5-endo-dig cyclization of ruthenium-vinylidene intermediate, a
      nonclassical ion formation, and the "methylenecyclopropane-trimethylenemethane"
      rearrangement.

PMID- 15563186
TI  - Inner-sphere electron-transfer reorganization energies of zinc porphyrins.
AB  - Inner-sphere electron-transfer reorganization energies of Zn(protoporphyrin IX)
      and Zn(octaethylporphyrin) are determined from band-shape analyses of the first
      ionization obtained by gas-phase valence photoelectron spectroscopy. The
      experimentally determined total inner-sphere reorganization energies for self
      exchange (120-140 meV) indicate that structural changes upon oxidation are
      largely confined to the porphyrin ring, and substituents on the ring or solvent
      and other environmental factors make smaller contributions. Computational
      estimates by different models vary over a wide range and are sensitive to
      numerical precision factors for these low reorganization energies. Of current
      computational models that are widely available and practical for molecules of
      this size, functionals that contain a mixture of Hartree-Fock exchange and DFT
      exchange-correlation appear to be the most applicable.

PMID- 15563187
TI  - Tin-chalcogen double-bond compounds, stannanethione and stannaneselone:
      synthesis, structure, and reactivities.
AB  - The first isolation of diarylstannanethione (tin-sulfur double-bond compound) and
      diarylstannaneselone (tin-selenium double-bond compound), Tbt(Ditp)Sn=X (Tbt =
      2,4,6-tris[bis(trimethylsilyl)methyl]phenyl; Ditp = 2,2' '-diisopropyl-m
      terphenyl-2'-yl; X = S and Se) was accomplished by dechalcogenation of the
      corresponding highly hindered tetrachalcogenastannolanes, Tbt(Ditp)SnX(4). The
      (119)Sn NMR of stannanethione, Tbt(Ditp)Sn=S, and stannaneselone, Tbt(Ditp)Sn=Se,
      showed only one low-field broad signal at 531 and 440 ppm, respectively,
      characteristic of a tricoordinated tin, and hence, the stannanethione and
      stannaneselone display an intrinsic nature of tin-chalcogen double-bond
      compounds. The X-ray crystallographic analysis of the isolated stannaneselone,
      Tbt(Ditp)Sn=Se 5a, revealed a completely trigonal geometry around the central tin
      with a remarkably short Sn-Se bond length, indicative of structural similarity to
      a ketone.

PMID- 15563188
TI  - Bimetallic palladium-gold dendrimer-encapsulated catalysts.
AB  - The synthesis, characterization, and catalytic properties of 1-3 nm-diameter
      bimetallic PdAu dendrimer-encapsulated catalysts are reported. Both alloy and
      core/shell PdAu nanoparticles were prepared. The catalytic hydrogenation of allyl
      alcohol was significantly enhanced in the presence of the alloy and core/shell
      PdAu nanoparticles as compared to mixtures of single-metal nanoparticles.

PMID- 15563189
TI  - Ruthenium-catalyzed enyne cycloisomerizations. Effect of allylic silyl ether on
      regioselectivity.
AB  - The ruthenium-catalyzed cycloisomerization of 1,6- and 1,7-enynes substituted in
      the terminal allylic position with a tert-butyldimethylsilyl ether group emerges
      as an effective reaction to form unprecedented five- or six-membered rings
      possessing a geometrically defined enol silane. Straightforward synthetic access
      to a variety of achiral 1,6- and 1,7-enynes, as well as chiral ones, is
      presented. Ruthenium catalysts effect efficiently such single-step
      cycloisomerization at room temperature in acetone under neutral conditions. The
      cycloisomerization functions with (E) or (Z) 1,2-disubstituted alkenes.
      Parameters influencing the enol silane geometry are discussed. The level of
      selectivity depends on the alkyne substitution, the geometry of the double bond,
      and the nature of the catalyst. Furthermore, examples of stereoinduction are
      shown and lead to highly substituted carbo- and heterocycles with excellent
      diastereocontrol.

PMID- 15563190
TI  - Structural and electron-transfer characteristics of O-, S-, and Se-tethered
      porphyrin monolayers on Si(100).
AB  - Monolayers of two classes of Zn porphyrins have been prepared and examined on
      Si(100). These molecules, designated as ZnPBzX- and ZnPCH2X-, contain either a
      benzyl (-Bz-) or a methylene (-CH2-) unit terminated with a Group VI atom (X = O,
      S, Se) appended to a meso-position of the porphyrin, with the nonlinking meso
      substituents consisting of either mesityl (-Bz- class) or p-tolyl and phenyl (
      CH2- class) units. The two series of ZnPBzX- and ZnPCH2X- monolayers on Si(100)
      were examined using a variety of techniques, including X-ray photoelectron
      spectroscopy, Fourier transform infrared spectroscopy, and various
      electrochemical methods. The studies reveal the following characteristics of the
      ZnPBzX- and ZnPCH2X- monolayers. (1) Surface binding can be readily achieved to
      Si(100) with both relatively short (-Bz-) and very short (-CH2-) tethers
      regardless of the nature of the Group VI anchoring atom (O, S, Se). (2) The
      longer -Bz- tether affords monolayers with the porphyrin ring in a somewhat more
      upright orientation with respect to the surface than the shorter -CH2- tether.
      The more upright adsorption geometry of the porphyrins bearing the former type of
      linker leads to a higher packing density and more homogeneous redox
      thermodynamics. (3) The kinetics of electron transfer does not depend on the type
      of Group VI atom used for anchoring to the Si(100) surface. On the other hand,
      the type of linker does affect the electron-transfer rates, with the monolayers
      bearing the -CH2- linker exhibiting systematically faster rates than those
      bearing the -Bz- linker. Collectively, the studies reported herein provide a
      detailed picture of how the anchor atom and the linker type influence the
      structural and electron-transfer characteristics of these general classes of
      monolayers.

PMID- 15563191
TI  - A substituent effects study reveals the kinetic pathway for an interfacial
      reaction.
AB  - This paper describes the use of a substituent effects study to understand the
      mechanistic basis for an interfacial Diels-Alder reaction that does not proceed
      with standard second-order kinetics. Cyclopentadiene (Cp) undergoes a Diels-Alder
      reaction with a chemisorbed mercaptobenzoquinone to yield an immobilized Diels
      Alder adduct. The pseudo-first-order rate constants are not linearly related to
      the concentration of diene, but they reach a limiting value with increasing
      concentrations of diene. The results of a substituent effects study support a
      mechanism wherein the electrochemical oxidation of hydroquinone produces two
      states of quinone. The first form, Q*, either reacts with Cp or isomerizes to Q,
      a form that is significantly less reactive with the diene. The interfacial
      reaction reaches a maximum rate when the concentration of diene is sufficiently
      high so that Q* undergoes complete Diels-Alder reaction and does not isomerize to
      Q. This work provides an example of the use of physical organic chemistry to
      understand an interfacial reaction.

PMID- 15563192
TI  - Full quantitative multiple-scattering analysis of X-ray absorption spectra:
      application to potassium hexacyanoferrat(II) and -(III) complexes.
AB  - A recently developed method to the full quantitative analysis of the XAS spectra
      extending from the absorption edge to the high-energy region is presented. This
      method is based on the use of two independent approaches to the analysis of the
      EXAFS and XANES data, the well-known GNXAS and the newly developed MXAN
      procedures. Herein, we report the application of this technique to two iron
      complexes of known structure where multiple-scattering effects are prominent, the
      potassium hexacyanoferrat(II) and -(III) crystals and aqueous solutions. The
      structural parameters obtained from refinements using the two methods are equal
      and compare quite well with crystallographic values. Small discrepancies between
      the experimental and calculated XANES spectra have been observed, and their
      origin has been investigated in the framework of non-muffin-tin correction. The
      ligand dependence of the theoretical spectra has been also examined. Analysis of
      the whole energy range of the XAS spectra has been found to be useful in
      elucidating both the type of ligands and the geometry of iron sites. These
      results are of particular use in studying the geometrical environment of metallic
      sites in proteins and complexes of chemical interest.

PMID- 15563193
TI  - One-bond spin-spin coupling constants of X-1H proton donors in complexes with X-H
      Y hydrogen bonds, for X = 13C, 15N, 17O, and 19F: predictions, comparisons, and
      relationships among 1J X-H, 1K X-H, and X-H distances.
AB  - Ab initio calculations at the equation-of-motion coupled cluster (EOM-CCSD) level
      of theory have been carried out to investigate one-bond (13)C-(1)H, (15)N-(1)H,
      (17)O-(1)H, and (19)F-(1)H coupling constants in a systematic study of monomers
      and hydrogen-bonded complexes. Computed coupling constants ((1)J(X-H)) for
      monomers are in good agreement with available experimental data. All reduced
      Fermi-contact terms and reduced coupling constants ((1)K(X-H)) for monomers and
      complexes are positive. Plots of (1)K(X-H) versus the X-H distance for the 16
      monomers and the 64 complexes in which these monomers are proton donors exhibit
      significant scatter. However, a linear relationship has been demonstrated for the
      first time between coupling constants and X-H distances for different X atoms by
      plotting the ratios of the coupling constants for complexes and corresponding
      monomers versus the ratios of distances for complexes and corresponding monomers
      times the square of the Pauling electronegativity. Since the ratio removes the
      dependence of coupling constants on the magnetogyric ratios of X, this
      relationship holds for both (1)K(X-H) and (1)J(X-H). The decrease in reduced
      coupling constants ((1)K(X-H)) as the X-H distance increases is due primarily to
      the increased proton-shared character of the hydrogen bond.

PMID- 15563194
TI  - Applying combinatorial chemistry and biology to food research.
AB  - In the past decade combinatorial chemistry has become a major focus of research
      activity in the pharmaceutical industry for accelerating the development of novel
      therapeutic compounds. The same combinatorial strategies could be applied to a
      broad spectrum of areas in agricultural and food research, including food safety
      and nutrition, development of product ingredients, and processing and conversion
      of natural products. In contrast to "rational design", the combinatorial approach
      relies on molecular diversity and high-throughput screening. The capability of
      exploring the structural and functional limits of a vast population of diverse
      chemical and biochemical molecules makes it possible to expedite the creation and
      isolation of compounds of desirable and useful properties. Several studies in
      recent years have demonstrated the utility of combinatorial methods for food
      research. These include the discovery of synthetic antimicrobial, antioxidative,
      and aflatoxin-binding peptides, the identification and analysis of unique flavor
      compounds, the generation of new enzyme inhibitors, the development of
      therapeutic antibodies for botulinum neurotoxins, the synthesis of unnatural
      polyketides and carotenoids, and the modification of food enzymes with novel
      properties. The results of such activities could open a large area of
      applications with potential benefits to the food industry. This review describes
      the current techniques of combinatorial chemistry and their applications, with
      emphasis on examples in food science research.

PMID- 15563195
TI  - Hyphenation of sorbent extraction and solid-matrix time-resolved luminescence
      using tetracycline in milk as a model analyte.
AB  - Hyphenation of sorbent extraction and solid-matrix time-resolved luminescence
      (TRL) was demonstrated using tetracycline (TC) in milk as a model analyte. The
      performance of a C18-impregnated silica layer was evaluated as both an extraction
      sorbent and a TRL substrate. To extract TC, a 10 x 6 mm glass-backed C18 layer
      was dipped into a 10 mL milk sample for 10 min followed by a 3-min water
      immersion for cleanup. The sorbent was then spotted with a TRL reagent solution
      at pH 9 that contained 5 mM europium nitrate and 5 mM EDTA. After a brief
      desiccation period, TRL was measured directly on the sorbent surface with a
      commercial fluorescence spectrophotometer. By eliminating the need to elute the
      analyte from the sorbent, organic solvent was not needed and sample preparation
      was greatly simplified. The integrated signal showed a linear dependence (R(2) =
      0.9938) on TC concentration in the 0-3000 microg/L range. The same protocol was
      applicable to screening TC in fat-free, 2% low-fat, and whole milk at 300
      microg/L, the US. regulatory tolerance level set by the Food and Drug
      Administration (FDA). This easy, fast, and low-cost screening method is friendly
      to the environment and particularly suitable for liquid samples.

PMID- 15563196
TI  - Development of an enzyme-linked immunosorbent assay for the detection of the
      fungicide fenarimol.
AB  - To develop an enzyme-linked immunosorbent assay for the fungicide fenarimol, two
      synthesized haptens, haptens-1 and -2, and the purchased 4,4'-DDA were conjugated
      to carrier proteins (BSA, KLH, and OVA). Polyclonal antibodies raised against
      hapten-1,2-KLH conjugates in rabbits and the coating antigens of hapten-1,2-BSA
      conjugates, hapten-2-OVA conjugate, and 4,4'-DDA-BSA conjugate were screened and
      selected for the homologous and/or heterologous ELISA formats. Two competitive
      indirect ELISAs were selected: assays I and II. The optimized ciELISAs of assays
      I and II showed average IC(50) values of fenarimol of 5.4 and 9.4 ng/mL,
      detection ranges of 1.1-25.9 and 1.1-82.7 ng/mL, and lowest detection limits of
      0.3 and 0.3 ng/mL, respectively. The cross-reactivities with several structurally
      related compounds indicated the importance of the steric fitness in the antigen
      antibody interaction. Recoveries of fenarimol from apple and pear samples spiked
      with the analyte by assay I were in the range of 93-113% by simple extraction,
      concentration, and dilution. This assay could be a convenient and supplemental
      analytical tool for monitoring fenarimol residues in environmental and
      agricultural samples.

PMID- 15563197
TI  - Loss of redness (a*) as a tool to follow hemoglobin-mediated lipid oxidation in
      washed cod mince.
AB  - Instrumental measurement of redness loss (decrease in a* value) was evaluated as
      a tool to follow hemoglobin (Hb)-mediated lipid oxidation in fish muscle. Two
      washed cod mince model systems were used (prepared at pH 6.5 and 5.5), both
      fortified with 15 micromol/kg of trout Hb and adjusted to pH 6.5 and 81%
      moisture. The rate of oxidation was varied through pH alterations (pH 6.1 and
      6.9) and addition of an antioxidative cod muscle press juice. During ice storage,
      TBARS, painty odor, and a* values were followed. In all "oxidizing" samples, a*
      values correlated well with TBARS and painty odor development; r = -0.95 and 
      0.77, respectively. In press juice containing samples, the correlation was lower
      (0.55 for a vs TBARS) because there was a slight a* value decrease even in the
      absence of measurable lipid oxidation. a* values distinguished between
      "oxidizing" and stable samples within 1 day, before any lipid oxidation products
      could be chemically detected. It was confirmed in an aqueous phosphate buffer
      model system that the redness loss corresponded to a buildup of brownish met-Hb
      at the expense of oxy- and deoxy-Hb. The a* value data were best used as a lipid
      oxidation index by calculating the rate of decrease (k value) in the "initial
      phase" of the redness loss (before accumulation of lipid oxidation products) or
      in the "differentiation phase" (during the exponential raise in TBARS/painty
      odor). Calibration to lipid oxidation products must, however, be made for each
      specific sample type. Washing method, pH, Hb-type, etc., all affected both k
      values and absolute a* readings. Small yellowness (b*) increases also occurred
      along with a value losses, possibly the result of polymerized Schiff bases.

PMID- 15563198
TI  - Development of a competitive ELISA for the evaluation of sunflower pollen in
      honey samples.
AB  - We report the development of a rapid, specific, and sensitive enzyme-linked
      immunoassay (ELISA) for the evaluation of sunflower pollen in honey as a method
      alternative to melissopalynology, which is considered the standard technique for
      the evaluation of floral origin of honey. Two 33-36 kDa proteins, identified as
      characteristic of sunflower pollen, were isolated and used as coating antigens in
      the competitive ELISA. We verified its analytical performance by evaluating
      reproducibility, specificity, and exactitude in relation to melissopalynology.
      The competitive ELISA developed during this work is able to quantify sunflower
      pollen in honey, with a detection limit of 10%, showing linear response between
      10 and 90%. The method afforded low cross reactivity with honey from other floral
      origin, thus evidencing an adequate selectivity. We also observed a significant
      correlation (r = 0.975; p < 0.001) when the proposed ELISA was referenced to
      melissopalynology. Hence, we conclude that the competitive ELISA constitutes a
      valuable and feasible alternative for authentication of sunflower honey. This
      work opens the possibility to develop similar assays for other pollen types.

PMID- 15563199
TI  - Parameters affecting extraction of selected fungicides from vineyard soils.
AB  - This paper describes a sensitive method for the simultaneous quantification of
      eight commonly used grapevine fungicides in vineyard soils: cyprodinil,
      fludioxonil, metalaxyl, penconazole, pyrimethanil, procymidone, tebuconazole, and
      vinclozolin. The fungicides are extracted from the soil sample by sonication with
      water followed by shaking with ethyl acetate and are quantified by gas
      chromatography with mass spectrometry. Average extraction efficiencies in a
      sample of seven spiked, previously fungicide-free soils were > or =79% for all of
      the analytes, method precisions were > or =17%, and quantification limits were <
      or =50 microg/kg. However, because recoveries varied considerably from soil to
      soil, there is a need to control for soil matrix differences (mainly soil pH and
      exchangeable calcium content); as a consequence, soil fungicide contents must be
      quantified by the standard additions method. When the method was applied in this
      way to soil samples from vineyards belonging to the specified wine-growing region
      of Rias Baixas (Galicia, northwestern Spain) taken at the beginning of October (1
      month after the crop's final treatment), levels of fludioxonil as high as 991
      microg/kg were found, but at the start of the season (9 months after the previous
      crop's final treatment) only fludioxonil was detected at levels higher than its
      limit of quantification (45 and 52 microg/kg).

PMID- 15563200
TI  - Simultaneous immunoaffinity column cleanup and HPLC analysis of aflatoxins and
      ochratoxin A in Spanish bee pollen.
AB  - Bee pollen is a major substrate for mycotoxins growth when no prompt and adequate
      drying is performed by the beekeeper after collection by bees. Regulatory limits
      for aflatoxins and ochratoxin A are currently in force in the European Union for
      a rising list of foodstuffs, but not for this. An immunoaffinity column cleanup
      process has been applied prior to the analysis of aflatoxins B(1), B(2), G(1),
      and G(2) and ochratoxin A (OTA). Optimization of the HPLC conditions has involved
      both a gradient elution and a wavelength program for the separation and
      fluorimetric quantitation of all five mycotoxins at their maximum excitation and
      emission values of wavelength in a single run. The higher limit of detection
      (mug/kg) was 0.49 for OTA and 0.20 for aflatoxin B(1). Repeatability (RSDr) at
      the lower limit tested ranged from 9.85% for OTA to 6.23% for aflatoxin G(2), and
      recoveries also at the lower spiked level were 73% for OTA and 81% for aflatoxin
      B(1). None of the 20 samples assayed showed quantifiable values for the five
      mycotoxins.

PMID- 15563201
TI  - Solid-phase microextraction-based approach to determine free-base nicotine in
      trapped mainstream cigarette smoke total particulate matter.
AB  - Characterizing nicotine delivery from tobacco products is important in the
      understanding of their addictive potential. Most previous studies report total
      nicotine and have not differentiated between nicotine in its protonated or free
      base form. Rather than simply determining total nicotine, the method described in
      this paper determines the amount of free-base nicotine associated with trapped
      mainstream smoke particulate matter generated using a standardized smoking
      machine protocol. This method quantitatively determines volatile free-base
      nicotine associated with the particulate phase portion of mainstream cigarette
      smoke using solid-phase microextraction combined with gas chromatography-mass
      spectrometry. The headspace above total particulate matter from mainstream
      cigarette smoke trapped on a Cambridge filter pad (CFP) was analyzed for free
      base nicotine in 26 cigarette brands. The selected cigarette brands were chosen
      to cover a wide range of tar and nicotine deliveries as measured under Federal
      Trade Commission machine smoking conditions. In the CFP's headspace the free-base
      nicotine levels ranged from 0.01 to 0.08 mg/cigarette. The measured ranges of
      free-base nicotine were remarkably similar over the different tar and nicotine
      delivery categories of full-flavored, light, and ultralight cigarette brands.

PMID- 15563202
TI  - Electrochemical evaluation of the inhibitory effects of weak acids on
      Zygosaccharomyces bailii.
AB  - The changes in intracellular redox activity or in mitochondrial electron
      transport could be taken as indications of the changes in the physiological state
      of living cells, based on which a mediated electrochemical method was purposed to
      evaluate the inhibitory effects of weak acids on Zygosaccharomyces bailii, a
      known food spoilage yeast. The dual mediator systems menadione/ferricyanide and
      2,6-dichlorophenolindophenol/ferricyanide were employed as probes to detect the
      variance in intracellular redox activity and in mitochondrial electron flux,
      respectively. Measurements were made with a microelectrode voltammetric method to
      assay the ferrocyanide accumulations arising from menadione- or 2,6
      dichlorophenolindophenol-mediated reduction of ferricyanide by Z. bailii
      suspensions by the presence or absence of increasing concentrations of weak
      acids. The results obtained from 2 h of incubation showed that the variance in
      electrochemical response revealed some physiological information underlying the
      inhibitory effects of weak acid on the yeast. For the first time, it was shown
      that the mediated electrochemical method provides an adjunct to the conventional
      method based on respiration inhibition for establishing levels for the
      utilization of preservatives in the food industry.

PMID- 15563203
TI  - Characterization of cigarette tobacco by direct electrospray ionization-ion trap
      mass spectrometry (ESI-ITMS) analysis of the aqueous extract--a novel and simple
      approach.
AB  - In support of the efforts to combat smuggling, as well as illegal sale and
      distribution of cigarettes, an analytical approach for the characterization of
      tobacco has been proposed and evaluated. It involves aqueous extraction of the
      filler tobaccos followed by direct analysis of the extracts by electrospray
      ionization-ion trap mass spectrometry (ESI-ITMS) in the negative mode. Typically,
      the deprotonated ions, [M - H](-), of organic acids (malic, citric, caffeic,
      quinic acid) and polyphenols (chlorogenic acid, rutin, scopoletin) were detected.
      MS/MS spectra of the ion at m/z 191, which is the [M - H](-) of quinic acid,
      citric acid, and scopoletin, and a fragment ion of chlorogenic acid were
      acquired. Significant differences in the MS and MS/MS spectra were observed
      between counterfeit samples and the corresponding authentic brand name
      cigarettes. Analysis of 25 commercial cigarettes showed that straight Virginia
      blends were readily distinguished from the blended products containing different
      tobacco types (Virginia, burley, and Oriental). The former exhibited consistently
      higher relative abundances of m/z 353 (chlorogenic acid) to m/z 133 (malic acid)
      in the MS spectra (0.9-1.2 vs 0.4-0.6) and higher intensity ratios of m/z 176
      (scopoletin) to m/z 173 (0.4-0.8 vs 0.1-0.3) and of m/z 127 (quinic acid) to m/z
      173 (0.7-1.0 vs 0.3-0.5) in the MS/MS spectra. Evidence is presented to
      demonstrate that the spectral differences were related not only to the tobacco
      type (Virginia, burley and Oriental) but also to the tobacco part (stem, lamina)
      used in the manufacture of the cigarettes.

PMID- 15563204
TI  - Profiling of soluble proteins in wine by nano-high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - Wine proteins play an important role in a wine's quality as they affect taste,
      clarity, and stability. To enhance our understanding of the proteins in wine,
      nano-high-performance liquid chromatography (HPLC)/tandem mass spectrometry was
      used to profile soluble proteins in wine. Twenty proteins were identified from a
      Sauvignon Blanc wine including five proteins derived from the grape, 12 from
      yeast, two from bacteria, and one from fungi. The findings are somewhat peculiar
      at first glance, but reasonable explanations can account for the results. The
      grape proteins identified are less in number, which may be due to the
      availability of an incomplete database and possibly bentonite fining. The
      relatively large number of identified yeast proteins may be due to their complete
      protein database. The identified bacterial and fungal proteins could possibly be
      attributed to sources in the vineyard including natural infections and improper
      handling during harvest. The use of nano-HPLC/tandem mass spectrometry is an
      important tool for identifying wine proteins and understanding how they affect
      its characteristics.

PMID- 15563205
TI  - Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and
      correlations with antioxidant levels.
AB  - The effects of 10 different extracts of fruits and berries on cell proliferation
      of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated. The
      fruits and berries used were rosehips, blueberries, black currant, black
      chokeberries, apple, sea buckthorn, plum, lingonberries, cherries, and
      raspberries. The extracts decreased the proliferation of both colon cancer cells
      HT29 and breast cancer cells MCF-7, and the effect was concentration dependent.
      The inhibition effect for the highest concentration of the extracts varied 2-3
      fold among the species, and it was in the ranges of 46-74% (average = 62%) for
      the HT29 cells and 24-68% (average = 52%) for the MCF-7 cells. There were great
      differences in the content of the analyzed antioxidants in the extracts. The
      level of the vitamin C content varied almost 100-fold, and the content of total
      carotenoids varied almost 150-fold among the species. Also in the composition and
      content of flavonols, hydroxycinnamic acids, anthocyanins, and phenolics were
      found great differences among the 10 species. The inhibition of cancer cell
      proliferation seen in these experiments correlated with levels of some
      carotenoids and with vitamin C levels, present at levels that can be found in
      human tissues. The same inhibition of cell proliferation could not be found by
      ascorbate standard alone. This correlation might indicate a synergistic effect of
      vitamin C and other substances. In MCF-7 cells, the anthocyanins may contribute
      to the inhibition of proliferation.

PMID- 15563206
TI  - Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and
      their antimicrobial activities.
AB  - A preliminary antimicrobial disk assay of chloroform, ethyl acetate, and n
      butanol extracts of artichoke (Cynara scolymus L.) leaf extracts showed that the
      n-butanol fraction exhibited the most significant antimicrobial activities
      against seven bacteria species, four yeasts, and four molds. Eight phenolic
      compounds were isolated from the n-butanol soluble fraction of artichoke leaf
      extracts. On the basis of high-performance liquid chromatography/electrospray
      ionization mass spectrometry, tandem mass spectrometry, and nuclear magnetic
      resonance techniques, the structures of the isolated compounds were determined as
      the four caffeoylquinic acid derivatives, chlorogenic acid (1), cynarin (2), 3,5
      di-O-caffeoylquinic acid (3), and 4,5-di-O-caffeoylquinic acid (4), and the four
      flavonoids, luteolin-7-rutinoside (5), cynaroside (6), apigenin-7-rutinoside (7),
      and apigenin-7-O-beta-D-glucopyranoside (8), respectively. The isolated compounds
      were examined for their antimicrobial activities on the above microorganisms,
      indicating that all eight phenolic compounds showed activity against most of the
      tested organisms. Among them, chlorogenic acid, cynarin, luteolin-7-rutinoside,
      and cynaroside exhibited a relatively higher activity than other compounds; in
      addition, they were more effective against fungi than bacteria. The minimum
      inhibitory concentrations of these compounds were between 50 and 200 microg/mL.

PMID- 15563207
TI  - Structural basis for antioxidant activity of trans-resveratrol: ab initio
      calculations and crystal and molecular structure.
AB  - From the experimental crystal structure and ab initio calculations on resveratrol
      and its derivatives, structural features of mechanistic importance are described.
      The molecular structure reveals the relative coplanarity of the trans-stilbene
      skeleton, and the molecular packing in the solid state shows an extensive
      hydrogen bond network that elucidates the flip-flop motion of the three hydroxyl
      groups that alternately form and break H bonds with each of the neighboring
      phenolic oxygens. The dynamic behavior provoked by the alternation of hydrogen
      bond formation and breaking can result in the ready mobility of up to three
      hydrogen atoms per resveratrol molecule that can be transferred to reactive
      oxidants that are rich in electron density. In addition, theoretical studies
      confirm the planarity of resveratrol as well as for half of the molecule of a
      condensation dimeric derivative of resveratrol, trans-sigma-viniferin.
      Furthermore, these studies show the p-4'-OH group to be more acidic compared to
      the other two m-OH groups. These features correlate with the biological activity
      of resveratrol as an antioxidant and support earlier studies showing H-atom
      transfer to be the dominant mechanism by which phenolic antioxidants intercept
      free radicals.

PMID- 15563208
TI  - Antioxidant activity and constituents of propolis collected in various areas of
      Korea.
AB  - Propolis is a resinous substance collected by honeybees from various plant
      sources. The composition of propolis depends on time, vegetation, and the area of
      collection. This study examined the antioxidant activity of propolis from various
      areas of Korea: Chilgok, Cheongju, Geochang, Muju, Pocheon, and Sangju. Ethanol
      extracts of propolis (EEP) were prepared and evaluated for their antioxidant
      activity by beta-carotene bleaching, 1,1-diphenyl-2-picrylhydrazyl free radical
      scavenging, and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical
      cation decolorization assays. Furthermore, the major constituents in EEP were
      identified by high-performance liquid chromatography analysis with a photodiode
      array and mass spectrometric detection, and each component was quantitatively
      analyzed. EEP from Cheongju and Muju had relatively strong antioxidant activity
      accompanied by high total polyphenol contents. Propolis from Cheongju contained
      large amounts of antioxidative compounds, such as caffeic acid, kaempferol, and
      phenethyl caffeate. On the other hand, propolis from Pocheon had compounds not
      seen in propolis from other areas.

PMID- 15563209
TI  - Treatment of dairy manure effluent using freshwater algae: elemental composition
      of algal biomass at different manure loading rates.
AB  - The cultivation of algae on nitrogen (N) and phosphorus (P) in animal manure
      effluents presents an alternative to the current practice of land application.
      However, the use and value of the resulting algal biomass as a feed or soil
      supplement depend, in part, on whether the biomass contains any harmful
      components such as heavy metals. The objective of this study was to determine how
      the elemental composition of algae changed in response to different loading rates
      of anaerobically digested flushed dairy manure effluent. Algal biomass was
      harvested weekly from laboratory-scale algal turf scrubber (ATS) units using four
      manure loading rates (2, 4, 6, or 9 L m(-2) day(-1)) corresponding to daily
      loading rates of 0.8-3.7 g of total N and 0.12-0.58 g of total P. Mean N and P
      contents in the dried biomass increased 1.6-1.8-fold with increasing loading rate
      up to maximums of 6.5% N and 0.84% P at 6 L m(-2) day(-1). Concentrations of Al,
      Ca, Cu, Fe, Mg, Mn, and Zn showed similar 1.4-1.8-fold increases up to maximums
      at a loading rate of 6 L m(-2) day(-1), followed by plateaus or decreases above
      this loading rate. Concentrations of Cd, Mo, and Pb initially increased with
      loading rate but then declined to levels comparable to those at the lowest
      loading rate. Concentrations of Si and K did not increase significantly with
      loading rate. The maximum concentrations of individual components in the algal
      biomass were as follows (in mg kg(-)(1)): 1100 (Al), 9700 (Ca), 0.43 (Cd), 56
      (Cu), 580 (Fe), 5.0 (Pb), 2300 (Mg), 240 (Mn), 3.0 (Mo), 14,700 (K), 210 (Si),
      and 290 (Zn). At these concentrations, heavy metals in the algal biomass would
      not be expected to reduce its value as a soil or feed amendment.

PMID- 15563210
TI  - Immunomodulatory activity of a new family of antioxidants obtained from grape
      polyphenols.
AB  - We examined the potential antioxidant activity and the immunopharmacological
      activity of new epicatechin conjugates obtained by depolymerization of grape
      polymeric flavanols in the presence of cysteamine or cysteine and with or without
      gallate. The compounds studied were (-)-epicatechin (1), cysteinyl-epicatechin
      (2), cysteamine-epicatechin (3), (-)-epicatechin gallate (4), cysteinyl
      epicatechin gallate (5), and cysteamine-epicatechin gallate (6) When incubated
      with an erythrocyte suspension, flavanols protected the erythrocyte membrane from
      hemolysis induced by 2,2'-azobis(2-amidinopropane) dihydrochloride, an azo free
      radical initiator. All the epicatechin derivatives tested were more efficient as
      antioxidant than epicatechin. The most potent antioxidant was compound 6. The
      compounds were tested for their capacity to modulate IL-1beta and IL-6, which are
      the main cytokine factors influencing the acute phase of the inflammatory
      response. (-)-Epicatechin and its related compounds inhibited the production of
      IL-1beta and IL-6 in whole blood incubated in the presence of Escherichia coli
      lipopolysaccharide. The most efficient inhibitor of cytokine formation was
      compound 3.

PMID- 15563211
TI  - Survival of freeze-dried Lactobacillus bulgaricus KFRI 673 in chitosan-coated
      calcium alginate microparticles.
AB  - The aim of this study was to investigate the effect of alginate microparticles
      coated with three kinds of chitosans of different molecular weights on the
      survival of Lactobacillus bulgaricus KFRI 673 in simulated gastric (SGJ) and
      intestinal juices (SIJ) and on their stability during storage at 4 and 22 degrees
      C. L. bulgaricus KFRI 673 loaded in alginate microparticles was prepared by
      spraying the mixture of sodium alginate and cell culture into the calcium
      chloride solution using an air-atomizing device. When L. bulgaricus KFRI 673 was
      exposed to SGJ of pH 2.0 for 60 min, none of the microorganism survived. Contrary
      to this result, microbiological analysis indicated that microencapsulation in
      alginate microparticles improved the survival of acid-sensitive L. bulgaricus
      KFRI 673 in SGJ and that high molecular weight chitosan coating resulted in the
      highest survival in SGJ. To study storage stability of free and microencapsulated
      cells, in vitro studies were conducted at 4 and 22 degrees C during a 4 week
      period. Both free and microencapsulated cells showed similar stabilities during 4
      weeks of storage at 4 degrees C. However, the stability of Lactobacillus at 22
      degrees C was appreciably improved when loaded in high molecular weight chitosan
      coated alginate microparticles. In conclusion, microencapsulation of lactic acid
      bacteria with alginate and chitosan coating offers an effective way of delivering
      viable bacterial cells to the colon and maintaining their survival during
      refrigerated storage.

PMID- 15563212
TI  - Effect of mash maceration on the polyphenolic content and visual quality
      attributes of cloudy apple juice.
AB  - The effects of enzymatic mash treatments on yield, turbidity, color, and
      polyphenolic content of cloudy apple juice were studied. Using HPLC-ESI-MS,
      cryptochlorogenic acid was identified in cv. Brettacher cloudy apple juice for
      the first time. Commercial pectolytic enzyme preparations with different levels
      of secondary protease activity were tested under both oxidative and nonoxidative
      conditions. Without the addition of ascorbic acid, oxidation substantially
      decreased chlorogenic acid, epicatechin, and procyanidin B2 contents due to
      enzymatic browning. The content of chlorogenic acid as the major polyphenolic
      compound was also influenced by the composition of pectolytic enzyme preparations
      because the presence of secondary protease activity resulted in a rise of
      chlorogenic acid. The latter effect was probably due to the inhibited protein
      polyphenol interactions, which prevented binding of polyphenolic compounds to the
      matrix, thus increasing their antioxidative potential. The results obtained
      clearly demonstrate the advantage of the nonoxidative mash maceration for the
      production of cloud-stable apple juice with a high polyphenolic content,
      particularly in a premature processing campaign.

PMID- 15563213
TI  - Processing of rice husk autohydrolysis liquors for obtaining food ingredients.
AB  - Rice husks are of a lignocellulosic nature, with a hemicellulose fraction made up
      of substituted arabinoxylan. Rice husks were treated with hot, compressed water
      (autohydrolysis reaction) under optimized conditions to cause the hydrolytic
      degradation of arabinoxylan. The reaction products contained volatile components
      and nonvolatile components (NVC), which were made up of hemicellulose-derived
      products (substituted oligosaccharides and monosaccharides) and other nonvolatile
      solutes (ONVS). To decrease the content of ONVS, concentrated autohydrolysis
      liquors were first subjected to ethyl acetate extraction and then subjected to
      various alternative treatments (solvent precipitation, freeze-drying solvent
      extraction, or ion exchange). The resulting liquors were assayed for composition
      and yield determination. Material balances are presented for the several
      processes considered. The best results in terms of purification were obtained
      with sequential stages of ethyl acetate extraction and ion exchange, which led to
      concentrates with hemicellulose-derived compounds (sugars and substituted sugar
      oligomers) accounting for 92 wt % of the NVCs.

PMID- 15563214
TI  - Glucosinolates and myrosinase activity in red cabbage (Brassica oleracea L. var.
      Capitata f. rubra DC.) after various microwave treatments.
AB  - Total and individual levels of glucosinolates (GSs) were measured in red cabbage
      after various microwave treatments varying in time and intensity of the
      treatments. Furthermore, the myrosinase enzyme activity of the microwave-heated
      vegetables was determined. The retention of GSs in the cabbage and the residual
      activity of the hydrolytic enzyme as a result of microwave preparation were
      compared with untreated cabbage. In general, high total GS levels were observed
      for all of the applied microwave treatments. Strikingly, many of the time/energy
      input combinations resulted in levels exceeding the total GS content of the
      untreated cabbage material. Moreover, the increase in levels seems to be
      associated with the energy input applied. A possible explanation for this
      behavior is an increased extractability of GS from heat-treated cabbage as
      compared to raw cabbage. Substantial myrosinase activity was retained in cabbage
      treated at low (24 min, 180 W) and intermediate microwave powers (8 min, 540 W)
      while microwave cooking for 4.8 min at 900 W (259.2 kJ energy input) resulted in
      a complete loss of hydrolytic activity. In this respect, differences in observed
      temperature profiles of the various microwave treatments play an important role.
      Higher retention of GSs and controllable amounts of active myrosinase can offer
      increasing health-promoting properties of microwave-prepared Brassica vegetables.

PMID- 15563215
TI  - Vitamin content and amino acid composition of pickled garlic processed with and
      without fermentation.
AB  - The effect of processing, with and without fermentation, upon the nutritional
      composition of pickled garlic was evaluated. On a dry basis, the fermented
      product had a higher content of riboflavin, alpha-tocopherol, and most individual
      amino acids but a lower thiamin level than the unfermented product. Ascorbic acid
      was totally lost during processing. The chemical scores for the unfermented and
      fermented product were 88 and 108%, respectively, with the limiting amino acid
      being leucine. Water blanching (90 degrees C for 4 min) affected only the
      ascorbic acid content, whereas fermentation significantly affected the contents
      of thiamin, ascorbic acid, and alpha-tocopherol, as well as glutamic acid and
      arginine. For each processing type, the effect of the preservation method and
      storage time on vitamins and amino acid composition was also analyzed. In the
      case of the fermented product, usage of the corresponding fermentation brine plus
      refrigerated storage was also assayed as the packing/preservation method and was
      found to give the best result from a nutritional standpoint.

PMID- 15563216
TI  - Characterization of anthocyanins and pyranoanthocyanins from blood orange [Citrus
      sinensis (L.) Osbeck] juice.
AB  - Anthocyanins from blood orange [Citrus sinensis (L.) Osbeck] juices were isolated
      and purified by means of high-speed countercurrent chromatography and preparative
      high-performance liquid chromatography. Structures of the pigments were then
      elucidated by electrospray ionization multiple mass spectrometry and nuclear
      magnetic resonance (NMR) spectroscopy. The major anthocyanins of the juice were
      characterized as cyanidin 3-glucoside and cyanidin 3-(6"-malonylglucoside).
      Furthermore, six minor anthocyanins were detected and identified as cyanidin 3,5
      diglucoside, delphinidin 3-glucoside, cyanidin 3-sophoroside, delphinidin 3-(6"
      malonylglucoside), peonidin 3-(6"-malonylglucoside), and cyanidin 3-(6"
      dioxalylglucoside). The occurrence of the latter compound in blood oranges is
      reported here for the first time, together with full NMR spectroscopic data.
      Further investigations revealed the presence of four anthocyanin-derived
      pigments, which are formed through a direct reaction between anthocyanins and
      hydroxycinnamic acids during prolonged storage of the juice. These novel
      pyranoanthocyanins were identified as the 4-vinylphenol, 4-vinylcatechol, 4
      vinylguaiacol, and 4-vinylsyringol adducts of cyanidin 3-glucoside through
      comparison of their mass spectrometric and chromatographic properties with those
      of synthesized reference compounds.

PMID- 15563217
TI  - Annual evolution of fatty acid profile from muscle lipids of the common carp
      (Cyprinus carpio) in Madagascar inland waters.
AB  - Annual evolution of muscle lipids fatty acid (FA) from common carp (Cyprinus
      carpio) has been determined in 2001 through monthly samplings in the reserve pond
      of Sisaony (SIS series) and Itasy Lake (ITA series) of the Madagascar highlands.
      Total lipids from muscle were extracted and quantified according to the Bligh and
      Dyer method. FA identification was performed by GC-MS of FA methyl esters and FA
      pyrrolidides and led to the identification of 41 FA; routine analyses of FA were
      made by capillary GC. Principal component analysis (PCA) was performed on the
      data set to compare FA profiles. Lipid content is low, ranging from 0.91 to 1.73%
      of wet muscle, with a low stage during the hot season (January-April) and a
      higher stage during the cold season (July-October). Three FA dominated the FA
      composition: oleic acid (17.0-21.5%), palmitic acid (13.1-16.1%), and linoleic
      acid (9.6-13.2%). Polyunsaturated fatty acids (PUFA) were present in appreciable
      amounts: arachidonic acid (AA; 2.9-5.9%), docosahexaenoic acid (DHA; 2.9-6.7%),
      eicosapentaenoic acid (EPA; 1.9-3.4%), and docosapentaenoic acid (DPA; 1.9-4.3%).
      Two opposite evolution schemes appear within two groups of FA; on the one hand
      PUFA (both n-3 and n-6 series) show a maximum in August-October and a minimum in
      January-April, and, on the other hand, oleic, palmitic, and linoleic acids show
      the opposite maxima and minima. PCA results give confirmation of these evolution
      schemes, the two groups of FA giving opposite high factor loadings on axis 1. The
      SIS and ITA series are differentiated by axis 2 by mean of minor FA, mostly odd-
      and branched-chain. Results indicate that common carp, the second most abundant
      freshwater fish in Madagascar highlands waters, may be an interesting source of
      dietary PUFA.

PMID- 15563218
TI  - Imaging molecular chemistry of Pioneer corn.
AB  - Synchrotron Fourier transform infrared (FTIR) microspectroscopy as a rapid,
      direct, and nondestructive analytical technique can explore molecular chemical
      features of the microstructure of biological samples. The objective of this study
      was to use synchrotron FTIR microspectroscopy to image the molecular chemistry of
      corn (cv. Pioneer 39P78) to reveal spatial intensity and distribution of chemical
      functional groups in corn tissue. This experiment was performed at the U2B
      station of the National Synchrotron Light Source in Brookhaven National
      Laboratory (NSLS-BNL, Upton, NY). The Pioneer corn tissue was imaged from the
      pericarp, seed coat, aleurone, and endosperm under peaks at 1736 (carbonyl C=O
      ester), 1510 (aromatic compound), 1650 (amide I), 1550 (amide II), 1246
      (cellulosic material), 1160 (CHO), 1150 (CHO), 1080 (CHO), 929 (CHO), 860 (CHO),
      3350 (OH and NH stretching), 2929 (CH(2) stretching band), and 2885 cm(-1) (CH(3)
      stretching band). The results showed that with synchrotron FTIR
      microspectroscopy, the images of the molecular chemistry of Pioneer corn could be
      generated. Such information on the microstructural-chemical features of grain
      corn can also be used for corn breeding programs for selecting superior varieties
      of corn for targeted food and feed purposes and for prediction of corn quality
      and nutritive value for humans and animals.

PMID- 15563219
TI  - Using synchrotron-based FTIR microspectroscopy to reveal chemical features of
      feather protein secondary structure: comparison with other feed protein sources.
AB  - Studying the secondary structure of proteins leads to an understanding of the
      components that make up a whole protein. An understanding of the structure of the
      whole protein is often vital to understanding its digestive behavior in animals
      and nutritive quality. Usually protein secondary structures include alpha-helix
      and beta-sheet. The percentages of these two structures in protein secondary
      structures may influence feed protein quality and digestive behavior. Feathers
      are widely available as a potential protein supplement. They are very high in
      protein (84%), but the digestibility of the protein is very low (5%). The
      objective of this study was to use synchrotron-based Fourier transform infrared
      (FTIR) microspectroscopy to reveal chemical features of feather protein secondary
      structure within amide I at ultraspatial resolution (pixel size = 10 x 10
      microm), in comparison with other protein sources from easily digested feeds such
      as barley, oat, and wheat tissue at endosperm regions (without destruction of
      their inherent structure). This experiment was performed at beamline U2B of the
      Albert Einstein Center for Synchrotron Biosciences at the National Synchrotron
      Light Source (NSLS) in Brookhaven National Laboratory (BNL), U.S. Dept of Energy
      (NSLS-BNL, Upton, NY). The results showed that ultraspatially resolved chemical
      imaging of feed protein secondary structure in terms of beta-sheet to alpha-helix
      peak height ratio by stepping in pixel-sized increments was obtained. Using
      synchrotron FTIR microspectroscopy can distinguish structures of protein amide I
      among the different feed protein sources. The results show that the secondary
      structure of feather protein differed from those of other feed protein sources in
      terms of the line-shape and position of amide I. The feather protein amide I
      peaked at approximately 1630 cm(-1). However, other feed protein sources showed a
      peak at approximately 1650 cm(-1). By using multicomponent peak modeling, the
      relatively quantitative amounts of alpha-helix and beta-sheet in protein
      secondary structure were obtained, which showed that feather contains 88% beta
      sheet and 4% alpha-helix, barley contains 17% beta-sheet and 71% alpha-helix, oat
      contains 2% beta-sheet and 92% alpha-helix, and wheat contains 42% beta-sheet and
      50% alpha-helix. The difference in percentage of protein secondary structure may
      be part of the reason for different feed protein digestive behaviors. These
      results demonstrate the potential of highly spatially resolved infrared
      microspectroscopy to reveal feed protein secondary structure. Information from
      this study by the infrared probing of feed protein secondary structure may be
      valuable as a guide for feed breeders to improve and maintain protein quality for
      animal use.

PMID- 15563220
TI  - Structural characterization, physicochemical properties, suspension stability,
      and adsorption properties of four solid forms of amitraz.
AB  - This paper reports the identification and preparation of three crystalline (A-C)
      and one metastable form (D) of amitraz. These were identified by their crystal
      morphology, crystal structures, aqueous solubility, and thermal properties. Form
      C was the least soluble (7 mug/mL) and had the highest melting point (115 degrees
      C). The differences in melting point (82 vs 72 degrees C) and solubility (20 vs
      23 mug/mL) of forms A and B were not significant. The metastable noncrystalline
      form D (Tg = 38 degrees C, transition temperature = 62 degrees C, and melting
      point = 78 degrees C) was obtained by deposition on the surface of activated
      carbon from acetonitrile solutions. When the anionic surfactant sodium lauryl
      sulfate was added to the solubility medium, the solubilities of forms A and B
      were increased 10-11-fold and that of form C was increased 28-fold. Changing the
      crystal form had an effect on the stability of amitraz suspensions. Form C was
      the most stable with a t(1/2) of 136 days, and form B was the least stable with a
      t(1/2) of 28 days. The stability correlated with solubility differences. The
      addition of sodium lauryl sulfate to the suspensions increased the rate of
      hydrolysis (mean t(1/2) = 17 h), and because of increased solubility, there was
      no difference in the stability of the crystal forms in the anionic surfactant
      solution.

PMID- 15563221
TI  - Influence of two insecticides, chlorpyrifos and quinalphos, on arginine
      ammonification and mineralizable nitrogen in two tropical soil types.
AB  - Effects of seed treatments with chlorpyrifos [5 g of active ingredient (ai) kg(
      1) of seed] and quinalphos (6.25 g of ai kg(-1) of seed) and standing crop
      treatments with chlorpyrifos (800 g of ai ha(-1)) and quinalphos (1000 g of ai
      ha(-1)) on arginine deamination and mineralizable nitrogen were monitored, in the
      sandy loam and loamy sand soils of two tropical semiarid fields, for three
      consecutive crop seasons. The arginine ammonification activity of rhizospheric
      microbes was inhibited after seed treatment with chlorpyrifos and quinalphos and
      their principal metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 3,5,6
      trichloro-2-methoxypyridine (TMP) and 2-hydroxyquinoxaline and quinoxaline-2
      thiol, respectively. Quinalphos produced transient inhibitions, whereas
      chlorpyrifos and its metabolites (TCP and TMP) exerted a greater inhibition in
      both loamy sand and sandy loam soils. Arginine ammonification by nonrhizospheric
      microbes was stimulated by standing crop treatments with both pesticides. In the
      loamy sand soil, the parent compounds stimulated rhizospheric N-mineralization,
      whereas the metabolites were inhibitory. However, nonrhizospheric N
      mineralization was inhibited by both chlorpyrifos and quinalphos and stimulated
      by their metabolites. A higher magnitude of inhibition of arginine deamination in
      the loamy sand than in the sandy loam soil could be due to greater
      bioavailability of the pesticides in the former, resulting from lesser sorption
      of the pesticides due to alkalinity of the soil and its low content of clay and
      organic carbon. Although both pesticides affected mineralizable nitrogen, seed
      treatment with quinalphos and standing crop treatment with quinalphos and
      chlorpyrifos produced the most significant effects. The recommended doses of the
      pesticides not only efficiently controlled whitegrubs, which increased pod
      yields, but also left no residues in harvested kernels. They also caused no long
      term inhibition of ammonification, which could have been of significant concern
      during the short crop period in semiarid areas where nitrogen determines plant
      productivity.

PMID- 15563222
TI  - Metabolism of metamitron in goat following a single oral administration of a
      nontoxic dose level: a continued study.
AB  - Disposition kinetic behavior and metabolism studies of metamitron and its
      metabolite in terms of the parent compound were carried out in black Bengal goats
      after a single oral administration of a nontoxic oral dose at 30 mg kg(-1) of
      body weight. Metamitron was detected in the blood sample at 5 min (2.23 +/- 0.04
      microg mL(-1)), maximum at 1 h (3.43 +/- 0.02 microg mL(-1)) and minimum at 12 h
      (0.41 +/- 0.01 microg mL(-1)), after a single oral administration. Metabolite [3
      methyl-6-phenyl-1,2,4-triazin-5(4H)-one] in terms of the parent compound was
      detected in the blood sample at 5 min (0.47 +/- 0.006 microg mL(-1)), maximum at
      6 h (5.12 +/- 0.02 microg mL(-1)) and minimum at 96 h (1.06 +/- 0.016 microg mL(
      1)), after a single oral administration. The t(1/2 K) and Cl(B) values of
      metamitron were 3.63 +/- 0.05 h and 1.36 +/- 0.016 L kg(-1) h(-1), respectively,
      whereas the t(1/2K)(m) and Cl(B)(m) values of the metabolite were 38.15 +/- 0.37
      h and 0.091 +/- 0.001 L kg(-1) h(-1), respectively, which suggested long
      persistence of the metabolite in blood and tissues of goat. Metamitron was
      excreted through feces and urine for up to 48 and 72 h, whereas the metabolite
      was excreted for up to 168 and 144 h, respectively. Metabolite alone contributed
      to 96 and 67% of combined recovery percentage of metamitron and metabolite
      against the administered dose in feces and urine of goat, respectively. All of
      the goat tissues except lung, adrenal gland, ovary, testis, and mammary gland
      retained the metabolite residue for up to 6 days after administration.

PMID- 15563223
TI  - Degradation and binding of atrazine in surface and subsurface soils.
AB  - Understanding the dissipation rates of chemicals in unsaturated and saturated
      zones of subsurface soils will help determine if reductions of concentrations to
      acceptable levels will occur. Chemical properties and microbial biomass and
      activity were determined for the surface (0-15 cm), lower root (50-105 cm), and
      vadose (175-220 cm) zones in a Huntington silty clay loam (Fluventic Hapludoll)
      collected from an agricultural field near Piketon, OH. The rates of sorption,
      mineralization, and transformation (formation of bound residues and metabolites)
      of atrazine were determined. Microbial activity was estimated from the
      mineralization of (14)C-benzoate. We observed decreased levels of nutrients
      (total organic carbon, N, and P) and microbial biomass with depth, while activity
      as measured with benzoate metabolism was higher in the vadose zone than in either
      the surface or the root zones. Sorption coefficients (K(f)) declined from 8.17 in
      the surface to 3.31 in the vadose zone. Sorption was positively correlated with
      organic C content. Rates of atrazine mineralization and bound residues formation
      were, respectively, 12-2.3-fold lower in the vadose than in the surface soil.
      Estimated half-lives of atrazine ranged from 77 to 101 days in the surface soil,
      but increased to over 900 days in the subsurface soils. The decreased dissipation
      of atrazine with increasing depth in the profile is the result of decreased
      microbial activity toward atrazine, measured either as total biomass or as
      populations of atrazine-degrading microorganisms. The combination of reduced
      dissipation and low sorption indicates that there is potential for atrazine
      movement in the subsurface soils.

PMID- 15563224
TI  - Free radicals scavenging efficiency of a few naturally occurring flavonoids: a
      comparative study.
AB  - The interaction of antiperoxidative flavonoids artocarpin (AR), cycloartocarpin
      (CAR), dalspinin (DP), dalspinosin (DPO), and dalspinin-7-O-galactoside (DPG)
      with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation
      (ABTS(.+)) and O2(-.) was studied in phosphate buffer (pH 7.4). The ability of
      these compounds to inhibit lipid peroxidation and DNA scission was also
      investigated. The radical scavenging efficiency of flavonoids is demonstrated by
      the reduction of nitrogen-centered radical cation (ABTS(.+)). The reduction of
      ABTS(.+) follows the order quercetin > morin > Trolox > AR > DPO > CAR > DP.
      Inhibition of lipid peroxidation was studied by following Mb(IV) reduction,
      induced by lipid, arachidonic acid. These results are compared with those
      obtained for well-known antioxidants such as quercetin, morin, and Trolox. The
      structure-activity relationships between chemical structures of the flavonoids
      and their radical scavenging activities are anlayzed. The scavenging of O2(-.),
      inhibition of lipid peroxidation, and DNA damage depend on the oxidation
      potential of the flavonoids. The possible mechanism for radical scavenging
      activities of flavonoids in relation to their structure is also outlined.

PMID- 15563225
TI  - Cytoprotection by neutral fraction of tannat red wine against oxidative stress
      induced cell death.
AB  - Some of the beneficial effects of the Mediterranean diet on human pathologies
      have been attributed to red wine polyphenols. It has been postulated that the
      antioxidant activity of the latter would be also responsible for the
      cytoprotective capacity of red wine that has been reported in a few papers.
      Nevertheless, red wine shows a complex composition, and the active fraction is
      not known yet. In this context, the protective capacity of total lyophilized
      extracts of red wine and anthocyanin, neutral, or acidic fractions, was explored
      in PC12 cells in culture after a hydrogen peroxide insult. Although all fractions
      showed high antioxidant activity, only the neutral fraction was cytoprotective.
      The analysis of this active fraction showed that it was rich in the aglycons
      quercetin and myricetin as well as the glycosides of kaempferol, isorhamnetin,
      epicatechin, and catechin, some of which are known to be cytoprotective. This is
      the first paper to reveal the active fraction of total wine responsible of its
      cytoprotection.

PMID- 15563226
TI  - Effects of pulsed electric fields on the activity and structure of pepsin.
AB  - A continuous pulsed electric field (PEF) system integrated with six co-field flow
      PEF treatment chambers was used to study the inactivation of pepsin. The
      inactivation of pepsin activity was a function of applied electric field
      strength, electrical conductivity, and pH. The inactivation of pepsin by PEF
      followed a first-order model. The first-order inactivation kinetic constant of
      pepsin was 0.012 (1/mus) in 7.5 mM HCl (pH 2.0) at 34.2 kV/cm. Aggregation of
      pepsin was observed during PEF treatment; however, the inactivation took place
      before the formation of aggregates. Circular dichroism analysis showed that
      inactivation of pepsin by PEF was correlated to the loss of beta-sheet structure
      in a pepsin molecule. The relative residual activity of PEF-treated pepsin was
      correlated to the relative molar ellipticity at 215 nm. Both PEF- and heat
      induced inactivation of pepsin were correlated with the alteration of the
      secondary structure (beta-sheet dominant structure) of pepsin.

PMID- 15563227
TI  - Purification and characterization of lipase in buckwheat seed.
AB  - To obtain basic information about enzymatic deterioration of buckwheat flour,
      triacylglycerol lipase (LIP; EC 3.1.1.3) was purified from buckwheat seed. The
      LIP consisted of two isozymes, LIP I and LIP II, and they were purified with
      purification folds of 60 and 143 with final specific activities of 0.108 and
      0.727 mumol of fatty acid released per minute per milligram of protein at 30
      degrees C using triolein as a substrate. Molecular weights were estimated to be
      150 (LIP I) and 28.4 kDa (LIP I) by gel filtration and 171 (LIP I) and 26.5 kDa
      (LIP II) by SDS-PAGE. Optimal pHs of LIP activities were 3.0 (LIP I) and 6.0 (Lip
      II) using triolein as a substrate. Both LIP I and II reacted in the acidic pH
      range. Optimal temperatures were 30 (LIP I) and 40 degrees C (LIP II), and both
      LIP I and II were stable below 30 degrees C when p-nitrophenyl-laurate was used
      as a substrate. However, they were inactivated above 60 degrees C. On the other
      hand, when triolein was used as a substrate, optimal temperatures were 30 degrees
      C for both LIP I and II, and they retained 40% of their activity after a 4 h
      incubation of enzymes at 70 degrees C. LIP I and II had higher activity against
      triolein than monoolein or tri/monopalmitin. Most of the LIP activity was
      distributed in the embryo.

PMID- 15563228
TI  - Activity, cloning, and expression of an isoamylase-type starch-debranching enzyme
      from banana fruit.
AB  - Unripe bananas have a high content of starch (almost 20%) that is metabolized
      during fruit ripening with a concomitant synthesis of soluble sugars. Since
      starch granules are composed of amylose and amylopectin, several enzymes have to
      be involved in its mobilization during banana ripening, with a necessary
      participation of one starch-debranching enzyme (DBE) to hydrolyze the alpha-1,6
      branches of amylopectin. Banana DBE seems to be an isoamylase-type enzyme, as
      indicated by substrate specificity and the cloning of a 1575 bp cDNA, similar to
      the isoamylase sequences from potato, Arabdopsis, and maize. The assays for DBE
      indicated only minor changes in activity during ripening, and the results of the
      northern and western blots with antiserum against the recombinant banana
      isoamylase were in agreement with the steady-state level of activity, since no
      significant changes in gene expression were observed. The high activity on beta
      limit dextrin and the similarity to the potato isoform 3 suggest that during
      banana ripening the hydrolysis of alpha-1,6-linkage of amylopectin results from
      the activity of a pre-existing isoamylase-type debranching enzyme in coordination
      with other amylolitic enzymes. To the best of our knowledge, this is the first
      evaluation of activity and expression of a DBE from a fruit.

PMID- 15563229
TI  - Inhibition of protein and lipid oxidation in liposomes by berry phenolics.
AB  - The antioxidant activity of berry phenolics (at concentrations of 1.4, 4.2, and
      8.4 mug of purified extracts/mL of liposome sample) such as anthocyanins,
      ellagitannins, and proanthocyanidins from raspberry (Rubus idaeus), bilberry
      (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), and black currant
      (Ribes nigrum) was investigated in a lactalbumin-liposome system. The extent of
      protein oxidation was measured by determining the loss of tryptophan fluorescence
      and formation of protein carbonyl compounds and that of lipid oxidation by
      conjugated diene hydroperoxides and hexanal analyses. The antioxidant protection
      toward lipid oxidation was best provided by lingonberry and bilberry phenolics
      followed by black currant and raspberry phenolics. Bilberry and raspberry
      phenolics exhibited the best overall antioxidant activity toward protein
      oxidation. Proanthocyanidins, especially the dimeric and trimeric forms, in
      lingonberries were among the most active phenolic constituents toward both lipid
      and protein oxidation. In bilberries and black currants, anthocyanins contributed
      the most to the antioxidant effect by inhibiting the formation of both hexanal
      and protein carbonyls. In raspberries, ellagitannins were responsible for the
      antioxidant activity. While the antioxidant effect of berry proanthocyanidins and
      anthocyanins was dose-dependent, ellagitannins appeared to be equally active at
      all concentrations. In conclusion, berries are rich in monomeric and polymeric
      phenolic compounds providing protection toward both lipid and protein oxidation.

PMID- 15563230
TI  - Novel approach for food safety evaluation. Results of a pilot experiment to
      evaluate organic and conventional foods.
AB  - There is evidence that organic food often contains relatively high amounts of
      natural toxic compounds produced by fungi or plants, whereas corresponding
      conventional food tends to contain more synthetic toxins such as pesticide
      residues, but only a few studies have evaluated the impact of their consumption
      on health. This study proposes a novel approach to evaluate the potential health
      risk of organic compared to conventional food consumption, that is, the assay of
      sensitive markers of cell function in vulnerable conditions. The markers utilized
      were intestinal and splenic lymphocyte proliferative capacity and liver acute
      phase reaction, both responding to the presence of toxins. The vulnerable
      conditions in which body defenses can be less efficient were weaning and protein
      energy malnutrition. This study reports the results of a pilot experiment on one
      sample of eight varieties of organically and conventionally grown wheat. Weaned
      rats were assigned to two groups fed conventional (CV) or organic (ORG) wheat for
      30 days. Each group was divided in two subgroups of well-nourished (WN) or
      protein-energy-malnourished (PEM) rats. For each rat, the lymphocyte
      proliferation was assayed by [(3)H]thymidine incorporation after stimulation of
      cells with a mitogen, in a culture medium containing either commercial fetal calf
      serum (FCS) or the corresponding rat serum (RS) to mimic the in vivo
      proliferative response. The acute-phase proteins (albumin, transthyretin,
      transferrin, ceruloplasmin, retinol-binding protein) were measured in plasma by
      Western blotting and immunostaining with specific antibodies. The proliferative
      response of lymphocytes cultured with FCS and the amount of acute-phase proteins
      of rats fed the ORG wheat sample, either WN or PEM, did not differ from those of
      rats fed the CV wheat sample. However, the proliferative response of lymphocytes
      cultured with RS was inhibited in PEM-CV compared with PEM-ORG. The content of
      mycotoxins was highest in the organic sample, and therefore the immunotoxic
      effect was probably due to other contaminants in the CV wheat. In conclusion,
      these results indicate that the conventional wheat sample tested represented a
      higher risk for lymphocyte function than the wheat sample organically grown, at
      least in vulnerable conditions.

PMID- 15563231
TI  - Comment on In vitro gastrointestinal digestion study of broccoli inflorescence
      phenolic compounds, glucosinolates, and vitamin C.

PMID- 15563234
TI  - Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and
      progressive multicentric glioma : a preliminary report.
AB  - OBJECTIVE: To evaluate the response rates, survival and toxicity of treatment
      with antineoplaston A10 and AS2-1 (ANP) in the first 12 children enrolled in our
      studies diagnosed with incurable recurrent and progressive multicentric glioma.
      PATIENTS AND METHODS: The patients' median age was 9 years. Six patients were
      diagnosed with pilocytic astrocytoma, four with low-grade astrocytoma and one
      with astrocytoma grade 2. In one case of visual pathway glioma, a biopsy was not
      performed due to a dangerous location. Patients received ANP intravenously
      initially and subsequently orally. The average duration of intravenous ANP
      therapy was 16 months and the average dosage of A10 was 7.95 g/kg/day and of AS2
      1 was 0.33 g/kg/day. The average duration of oral ANP was 19 months and the
      average dosage of A10 and AS2-1 was 0.28 g/kg/day. Responses were assessed by MRI
      according to the National Cancer Institute's criteria and confirmed by PET scans
      in some cases. RESULTS: Complete response was accomplished in 33%, partial
      response in 25%, and stable disease in 33% of patients, and there was no
      progressive disease. One patient was non-evaluable due to only 4 weeks of ANP and
      lack of follow-up scans. One patient who had stable disease discontinued ANP
      against medical advice and died 4.5 years later. Ten patients are alive and well
      from 2 to >14 years post-diagnosis. Only one case of serious toxicity of
      reversible tinnitus, of one day's duration, was described. The study continues
      with accrual of additional patients. CONCLUSION: The results of the present study
      are favourable in comparison with radiation therapy and chemotherapy. We believe
      that confirmation of these results through further studies may introduce a new
      promising treatment for incurable paediatric brain tumours.

PMID- 15563235
TI  - In vitro effects of selective and non-selective nonsteroidal anti-inflammatory
      drugs on the frequency of sister chromatid exchanges.

PMID- 15563236
TI  - Effect of D-003 on a subconvulsive dose of kainic Acid in rats.

PMID- 15563237
TI  - Gadofosveset: MS 325, MS 32520, Vasovist, ZK 236018.
AB  - Gadofosveset [MS 325, MS 32520, Vasovist, ZK 236018], a gadolinium-based chelate,
      is an injectable angiography imaging agent for use in magnetic resonance imaging
      (MRI) scans. The agent is being developed by EPIX Medical (formerly Metasyn) for
      diagnostic imaging of blood vessels of the cardiovascular system. Gadofosveset
      has potential as an alternative to the range of x-ray, invasive, catheter-based
      angiograms and thallium stress tests currently used in the diagnosis of coronary
      artery disease. The agent may also have applications in the diagnosis of
      peripheral vascular disease, thrombosis and breast cancer. Unlike conventional
      MRI contrast agents, gadofosveset binds to serum albumin in the blood and moves
      with the blood through the arteries and veins for an extended period of time
      before being excreted by the kidneys. The MRI with gadofosveset allows 3D images
      of the whole body to be accessed in one imaging session. Moreover, it makes it
      possible to view vessel structures.EPIX Medical has acquired an exclusive licence
      from the Massachusetts General Hospital to a certain technology, including
      patents and patent applications, that relates to the company's product candidates
      such as gadofosveset.EPIX Medical, Mallinckrodt (Tyco International) and Schering
      AG signed several agreements to develop, manufacture and market gadofosveset
      (formerly known as Mallinckrodt's AngioMARK). Initially, in June 2000 Schering AG
      acquired worldwide exclusive rights (except for Japan) from EPIX Medical to
      develop and market gadofosveset. Under the terms of the agreement, EPIX Medical
      is responsible for the completion of clinical trials and filing for approval in
      the US, while Schering AG undertakes responsibility for clinical investigation of
      gadofosveset outside the US. Mallinckrodt is responsible and will undertake a
      long-term supply contract for gadofosveset for clinical development and sales.
      Schering's subsidiary Berlex will market the product in the US after the approval
      via its 100 sales representatives. In January 2001, EPIX Medical reacquired the
      Japanese rights for gadofosveset from Daiichi Radioisotope Laboratories and
      exclusively licensed them to Schering AG. With this agreement, Schering AG has
      worldwide rights for gadofosveset. The financial terms of the Japanese rights
      agreement included a US$3 million upfront fee, and additional milestone payments
      from Schering AG to EPIX Medical. On 16 December 2003, EPIX announced that it
      submitted an NDA to the US FDA for gadofosveset for vascular imaging using
      magnetic resonance angio-graphy (MRA). This is the first NDA filed for approval
      with the FDA for a MR contrast agent for the primary indication of MRA. The NDA
      is based on the results of 18 clinical trials in 1438 patients who received
      gadofosveset. In February 2004, EPIX Medical announced that the NDA for
      gadofosveset was accepted for filing by the FDA and would proceed through a
      standard review cycle. The approval for gadofosveset is expected at the end of
      2004. In January 2004, Schering reported at the JP Morgan Healthcare Conference
      that it plans a product launch in the US sometime in 2005.EPIX and Schering have
      completed four phase III studies in patients with suspected atherosclerotic
      disease in the aortoilliac, pedal and renal arteries for inclusion in the NDA
      submission. These trials were conducted at 86 clinical sites and involved 782
      patients. The blinded reading of almost 4000 vessels showed that gadofosveset
      improved diagnostic accuracy of MRA compared with non-contrast MRA. The
      diagnostic efficacy of gadofosveset-enhanced MRA was comparable to that of x-ray
      angiography. These trials were initiated in accordance with the recommendations
      of the FDA to expand gadofosveset's target indication of aortoiliac occlusive
      disease to a broader peripheral vascular disease indication. In July 2004, EPIX
      Medical initiated a multicentre, post-NDA trial with gadofosveset for use in high
      resolution vessel imaging for the characterisation of vascular wall structures
      and vulnerable plaque. The trial will investigate whether gadofosveset has an
      extended imaging window above and beyond that which was demonstrated in phase III
      studies. In June 2004, Schering submitted gadofosveset for approval in Europe for
      use as a conrast agent for MRA. The launch in Europe is projected for 2006
      (Schering, Annual Report 2003). Schering has initiated its first feasibility,
      multicentre (Europe, US), phase III clinical trial with gadofosveset for the
      imaging of coronary artery disease in approximately 50 patients. This trial
      follows a successful completion of phase II feasibility studies with gadofosveset
      in the imaging of coronary artery disease and breast tumour imaging. In July
      2004, EPIX announced that it initiated a multicentre phase IIa feasibility
      clinical trial with gadofosveset in the imaging of both the coronary arteries and
      myocardial perfusion.EPIX Medical is conducting preclinical investigation with
      gadofosveset for myocardial perfusion and rheumatoid arthritis.EPIX Medical,
      Mallinckrodt and Pfizer have announced a collaboration to investigate MRI imaging
      with gadofosveset in the diagnosis and monitoring of female sexual arousal
      dysfunction (FSAG). EPIX Medical completed enrolment in a phase II clinical
      feasibility trial using gadofosveset for this indication. It is estimated that
      more than 10 million women in the US suffer from FSAD.EPIX Medical was granted a
      US patent No. 6,676,929 covering composition-of-matter claims for the chemical
      structure of gadofosveset. The patent is entitled "Diagnostic Imaging Contrast
      Agents With Extended Blood Retention". Its expiry date is August 2015. However,
      under provision of the Hatch-Waxman Act, the terms of the patent may be extended
      following FDA approval. In its 2002 Annual Report, Schering predicted that
      gadofosveset has the potential to reach peak sales of EUR100 million, 3 years
      after launch - at the time, launch in the US was anticipated in 2005. Earlier, at
      an analyst presentation in Berlin in March 2002, the company stated that launch
      in the US was planned for 2004.

PMID- 15563238
TI  - Icatibant: HOE 140, JE 049, JE049.
AB  - Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic
      bradykinin beta2-receptor antagonist. It has a modified peptide structure, and is
      the first bradykinin receptor antagonist to act on the guinea-pig trachea without
      demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel
      (now Sanofi-Aventis). Jerini is seeking a partner for development and marketing
      of icatibant for the treatment of refractory ascites in liver cirrhosis,
      angioedema and burns. In August 2004, Aventis merged with Sanofi-Synthelabo to
      form Sanofi-Aventis.Icatibant has shown an excellent safety profile in phase I
      studies. In December 2003, Jerini demonstrated positive results in the phase IIa
      study. Results obtained were statistically significant and clinically relevant.
      At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA,
      USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb trials in this
      indication in the second half of 2004. Positive results from an icatibant
      formulation comparative study, in patients with acute attacks of hereditary
      angioedema, were announced in August 2004; IV and SC formulations showed no
      difference in efficacy and safety. It was announced in September 2004 by Jerini
      that a pivotal study, known as For Angioedema Subcutaneous Treatment (FAST) 1,
      had been initiated in the US and Canada. The protocol of a European study, to be
      known as FAST 2, is to be submitted to the authorities in September 2004. Jerini
      expects to launch the product in 2006. The US FDA granted icatibant, for the
      treatment of hereditary angioedema, fast-track designation in July 2004. In
      January 2003, the European Agency for the Evaluation of Medicinal Products
      granted icatibant orphan drug status in Europe for the treatment of angioedema.
      In November 2003, Jerini announced that effective December 2003, icatibant had
      orphan drug status in the US for the same indication.

PMID- 15563239
TI  - Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate
      powder-Santarus, SAN 05.
AB  - Santarus Inc. is developing an immediate-release formulation of omeprazole in
      combination with an antacid (sodium bicarbonate) as a powder for suspension,
      known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral
      suspension. This omeprazole powder suspension will be used to treat
      gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and
      peptic ulcers. Acitreltrade mark is based on technology licensed from the
      University of Missouri. Santarus have also licensed technology from Tulane and
      North Carolina Universities relating to potential treatments for gastrointestinal
      (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent
      applications covering specific combination formulations of proton pump inhibitors
      (PPIs) and antacids for treating various upper GI diseases and disorders.
      Santarus plans to license the development, distribution and marketing rights of
      omeprazole powder for oral suspension 20 mg outside the US, to one or more well
      established pharmaceutical companies. The US FDA has requested that Santarus
      pursue a name other than Rapinex for the product. Santarus is currently
      discussing potential alternative names for the product with the FDA. Santarus
      announced positive results in August 2003 from a phase III trial comparing oral
      Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI
      bleeding in 359 critically ill adult patients. Santarus has also completed an
      open-label clinical trial in 243 patients, including 97 patients with gastric
      ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8
      week period. In connection with the NDA for omeprazole powder suspension 40 mg,
      Santarus provided notice to the NDA holder for Prilosec delayed-release capsules
      and related patent owners that omeprazole powder suspension 40 mg does not
      infringe currently listed patents for Prilosec or that those patents are invalid.

PMID- 15563240
TI  - Palifermin: AMJ 9701, KGF-Amgen, recombinant human keratinocyte growth factor,
      rHu-KGF.
AB  - Amgen is developing a recombinant human form of keratinocyte growth factor (rHu
      KGF) called palifermin [AMJ 9701]. Keratinocyte growth factor (KGF, fibroblast
      growth factor 7, FGF-7) is a form of an endogenous epithelial tissue growth
      factor that stimulates the growth of cells on the surface of the gastrointestinal
      tract. Palifermin is being developed for oral mucositis (stomatitis), for which
      it is undergoing review by the US FDA.At BioSquare-2004, Biovitrum stated that it
      has entered into an agreement with Amgen, under which Biovitrium has co-promotion
      rights to palifermin in Nordic countries, including Scandinavia and Iceland.
      Amgen also plans to investigate the efficacy and safety of palifermin in patients
      with oral mucositis associated with other forms of chemotherapy. Amgen has stated
      that palifermin is also undergoing phase II trials in patients with solid
      tumours.

PMID- 15563241
TI  - Safinamide: FCE 26743, NW 1015, PNU 151774, PNU 151774E.
AB  - Safinamide [NW 1015, PNU 151774E; FCE 26743] is a potent anticonvulsant and
      antiparkinsonian compound that is being developed by Newron Pharmaceuticals in
      Europe. It has been shown to antagonise the calcium and sodium channels, as well
      as inhibit monoamine oxidase type-B (MAO-B). Phase III trials for the treatment
      of Parkinson's disease are underway in Germany and Europe, while phase II trials
      in patients with epilepsy are ongoing in Italy. Newron Pharmaceuticals was
      founded at the end of 1998 after Pharmacia & Upjohn announced its worldwide
      restructuring programme. Newron obtained the rights to safinamide, which
      Pharmacia Corporation (now Pfizer) had been developing as PNU 151774E. Safinamide
      was originated by Farmitalia-CarloErba in Italy. Newron now owns all intellectual
      property associated with the drug.A multinational phase II trial for Parkinson's
      disease in Europe has shown positive results in slowing the progression of the
      disease; however, due to the placebo-effect seen in this study, a longer (6
      month) phase IIb study is planned for the second quarter of 2003. In July 2003,
      Newron received an IND from the US FDA authorising a phase I trial to confirm
      that no dietary restrictions are needed in patients while being treated with
      safinamide. This study is be conducted in 12 healthy volunteers at the University
      of Vienna, Austria, and will be followed by efficacy studies in Parkinson's
      disease in the US. Five phase I trials were completed in April 2001 in
      Switzerland. Safinamide combines sodium and calcium channel modulatory activity
      with monoamine oxidase B inhibition.

PMID- 15563242
TI  - Tamibarotene: AM 80, retinobenzoic acid, Tamibaro.
AB  - Tamibarotene [AM 80, retinobenzoic acid, Amnoid, Tamibaro] is a novel synthetic
      retinoid that is in development with Nippon Shinyaku as a potential treatment for
      acute promyelocytic leukaemia (APL) and is pending approval in Japan.
      Tamibarotene was being developed by Shionogi in Japan but the company
      subsequently discontinued its involvement. Various nonindustrial sources, such as
      the University of Tokyo, Japan, have also played a role in the development of
      tamibarotene. Nippon Shinyaku has licensed the rights to tamibarotene from Toko
      Pharmaceutical Industries for the treatment of acute promyelocytic leukaemia,
      according to Nippon Shinyaku's June 2004 pipeline update. However it is unclear
      when Toko Pharmaceutical Industries acquired rights to the compound.

PMID- 15563243
TI  - Temsirolimus: CCI 779, CCI-779, cell cycle inhibitor-779.
AB  - Wyeth (formerly American Home Products) is developing temsirolimus [Cell cycle
      inhibitor-779, CCI 779], an ester analogue of sirolimus, for the treatment of
      cancer, multiple sclerosis and rheumatoid arthritis. Temsirolimus binds to the
      cytosolic protein, FKBP, which subsequently inhibits mTOR (mammalian target of
      rapamycin). Inhibition of mTOR blocks a number of signal transduction pathways
      that suppress translation of several key proteins regulating the cell cycle.
      These effects lead to a cell cycle block at the G1 phase. In animal models of
      human cancers, temsirolimus inhibited the growth of a diverse range of cancer
      types even when an intermittent dosing schedule was used. The compound also
      appears to have potential for the blockade of inflammatory responses associated
      with autoimmune and rheumatic diseases by inhibiting T-cell proliferation. On 11
      March 2002, American Home Products changed its name and the name of its
      subsidiary Wyeth-Ayerst to Wyeth. During the first half of 2004, Wyeth initiated
      ongoing recruitment into a US phase III trial comparing orally administered
      temsirolimus plus letrozole versus letrozole alone as first-line treatment among
      approximately 1200 postmenopausal women with advanced breast cancer. The
      multicentre, randomised, double-blind, placebo-controlled trial is estimated to
      last 34 months. All subjects will have the option of participating in the long
      term follow-up phase of the trial that involves follow-up every 3 months until
      disease progression; the primary endpoint is overall progression-free survival.
      In August 2004, the US FDA granted temsirolimus fast-track status for the first
      line treatment of poor-prognosis patients with advanced renal cell carcinoma.
      Previously in March 2002, temsirolimus received fast-track status from the FDA
      for the treatment of renal cell carcinoma in patients who failed to respond to
      interleukin-2 treatment. Wyeth intends to file a NDA for temsirolimus for this
      indication by 2006. Researchers from Wyeth presented the findings from a
      preclinical study of temsirolimus at the 67th Annual Scientific Meeting of the
      American College of Rheumatology and the 38th Annual Meeting Association of
      Rheumatology Health Professionals (ACR/ARHP-2003) [Orlando, FL, USA; October
      2003]. The aim of this study was to determine the effect of temsirolimus on
      lymphocyte proliferation and cytokine production. Since lymphocytes and cytokines
      are significantly involved in the pathogenesis of rheumatoid arthritis,
      temsirolimus could have disease-modifying antirheumatic drug (DMARD) activity
      against rheumatoid arthritis via the inhibition of these factors. According to
      Wyeth's investor presentation in June 2004, the patent covering temsirolimus is
      due for expiry in 2014.

PMID- 15563244
TI  - Testosterone Undecanoate-Schering AG.
AB  - Schering AG is developing a formulation of testosterone undecanoate [Nebido] for
      the treatment of testosterone deficiency or hypogonadism. This deficiency can
      lead to decreased muscle mass, impaired muscle function, osteoporosis, reduced
      sexual function and mental degeneration. Schering claims that its new formulation
      provides superior control of blood levels of the drug and permits a longer period
      of application. Nebido requires only four injections per year, and represents a
      major improvement for men with testosterone deficiency. Schering AG received
      approval of its testosterone undecanoate formulation in its first European
      country, Finland, in November 2003 for the treatment of hypogonadism in men. In
      July 2004, Schering's testosterone undecanoate formulation completed approval of
      the European mutual recognition procedure. This approval clears the way for
      marketing the product (as Nebido) in the large pharmaceutical markets like
      Germany, France and the UK. The initial phase of the product launch will occur in
      Finland in October 2004, and in Germany in November 2004. Other European
      countries will follow in 2005, and following receipt of approval, it will be
      introduced in the first Latin American and Asian countries. In its 2002 Annual
      Report, Schering predicted that testosterone undecanoate has the potential to
      reach peak sales of euro 100 million, 3 years after launch-launch in Europe was
      at the time anticipated in 2004.

PMID- 15563246
TI  - The role of olmesartan medoxomil in the management of hypertension.
AB  - Intensive blood pressure control is a desirable and obtainable goal in patients
      with hypertension, according to the most recent treatment guidelines from Europe
      and the US. Achieving target blood pressure depends on the efficacy of
      antihypertensive treatment and patient compliance. Olmesartan medoxomil, a non
      peptidergic angiotensin AT1 receptor antagonist, has been shown to be effective
      and well tolerated. Continuation of initial treatment is higher with AT1 receptor
      antagonists than for any other class of antihypertensive drugs. Olmesartan
      medoxomil may also have end-organ protective effects that provide additional
      clinical benefit. Optimal blood pressure control may be achieved faster if
      initial treatment contains the most efficacious and well tolerated
      antihypertensive drug or drugs. The ongoing European study, known as OLMEBEST
      (Efficacy and safety of OLMEsartan: reduction of Blood pressure in the treatment
      of patients suffering from mild to moderate ESsenTial hypertension), will provide
      important information on the use of olmesartan medoxomil as an initial treatment
      for hypertension.

PMID- 15563247
TI  - Pharmacological cardioversion of atrial fibrillation: current management and
      treatment options.
AB  - Atrial fibrillation (AF) is the most common form of arrhythmia, carrying high
      social costs. It is usually first seen by general practitioners or in emergency
      departments. Despite the availability of consensus guidelines, considerable
      variations exist in treatment practice, especially outside specialised
      cardiological settings. Cardioversion to sinus rhythm aims to: (i) restore the
      atrial contribution to ventricular filling/output; (ii) regularise ventricular
      rate; and (iii) interrupt atrial remodelling. Cardioversion always requires
      careful assessment of potential proarrhythmic and thromboembolic risks, and this
      translates into the need to personalise treatment decisions. Among the many
      clinical variables that affect strategy selection, time from onset is crucial. In
      selected patients, pharmacological cardioversion of recent-onset AF can be a
      safely used, feasible and effective approach, even in internal medicine and
      emergency departments. In most cases of recent-onset AF, pharmacological
      cardioversion provides an important--and probably more cost effective-
      alternative to electrical cardioversion, which can then be employed as a second
      line therapy for nonresponders. Class IC agents (flecainide or propafenone),
      which can be safely used in hospitalised patients with recent-onset AF without
      left ventricular dysfunction, can provide rapid conversion to sinus rhythm after
      either intravenous administration or oral loading. Although intravenous
      amiodarone requires longer conversion times, it is still the standard treatment
      for patients with heart failure. Ibutilide also provides good conversion rates
      and could be used for AF patients with left ventricular dysfunction (were it not
      for high costs). For long-lasting AF most pharmacological treatments have only
      limited efficacy and electrical cardioversion remains the gold standard in this
      setting. However, a widely used strategy involves pretreatment with amiodarone in
      the weeks before planned electrical cardioversion: this provides optimal
      prophylaxis and can sometimes even restore sinus rhythm. Dofetilide may also be
      capable of restoring sinus rhythm in up to 25-30% of patients and can be used in
      patients with heart failure. The potential risk of proarrhythmia increases the
      need for careful therapeutic decision making and management of pharmacological
      cardioversion. The results of recent trials (AFFIRM [Atrial Fibrillation Follow
      up Investigation of Rhythm Management] and RACE [Rate Control versus Electrical
      Cardioversion for Persistent Atrial Fibrillation]) on rate versus rhythm control
      strategies in the long term have led to a generalised shift in interest towards
      rate control. Although carefully designed studies are required to better define
      the role of pharmacological rhythm control in specific AF settings, this
      alternative option remains a recommendable strategy for many patients, especially
      those in acute care.

PMID- 15563248
TI  - Viral prophylaxis in organ transplant patients.
AB  - Viral pathogens have emerged as the most important microbial agents having
      deleterious effects on solid organ transplant (SOT) recipients. Antiviral
      chemoprophylaxis involves the administration of medications to abort transmission
      of, avoid reactivation of, or prevent progression to disease from, active viral
      infection. Cytomegalovirus (CMV) is the major microbial pathogen having a
      negative effect on SOT recipients. CMV causes infectious disease syndromes,
      augments iatrogenic immunosuppression and is commonly associated with
      opportunistic superinfection. CMV has also been implicated in the pathogenesis of
      rejection. Chemoprophylactic regimens for CMV have included oral aciclovir
      (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the
      prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic
      strategies should be stratified, with the highest-risk patients receiving the
      most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in
      SOT recipients is more frequent, may become more invasive, takes longer to heal,
      and has greater potential for dissemination to visceral organs than it does in
      the immunocompetent host. Prophylactic regimens for CMV are also effective
      chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir,
      valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive
      recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most
      commonly seen in the paediatric transplant population because of VZV
      epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post
      transplant month. Prophylactic regimens for zoster are neither practical nor cost
      effective after SOT because of the late onset of disease and low proportion of
      affected individuals. All SOT recipients should receive VZV immune globulin after
      contact with either varicella or zoster. Epstein-Barr virus has its most
      significant effect in SOT as the precipitating factor in the development of post
      transplant lymphoproliferative disorders. Antiviral agents that could be
      effective are the same as those used for CMV, but indications for and
      effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and
      hepatitis C virus (HCV) are important pathogens in the SOT population as
      indications for transplantation. So-called 'prophylaxis' for recurrent HBV and
      HCV after liver transplantation is controversial, suppressive rather than
      preventive, and potentially lifelong. Influenza infection after SOT is acquired
      by person-to-person contact. During epidemic periods of influenza, transplant
      populations experience a relatively high frequency of infection, and influenza
      may affect immunosuppressed SOT recipients more adversely than immunocompetent
      individuals. Antiviral medications for prevention of influenza are administered
      as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in
      circumstances such as influenza epidemics and nosocomial outbreaks, and after
      exposure to a symptomatic individual during 'flu season'.

PMID- 15563249
TI  - Structure-modifying capacity of anti-tumour necrosis factor-alpha therapy in
      ankylosing spondylitis.
AB  - Spondylarthropathies (SpA) present mainly with spondylitis, pauciarticular
      peripheral arthritis and enthesopathy. Ankylosing spondylitis (AS) is the
      prototype disease in this concept. Other entities include reactive arthritis,
      arthritis in patients with inflammatory bowel disease, some forms of psoriatic
      arthritis and undifferentiated SpA. NSAIDs are the classical cornerstone of
      medical therapy in patients with SpA. The effect of these drugs on disease
      progression, more specifically the ankylosis, is uncertain. Sulfasalazine can be
      combined with NSAIDs, particularly if peripheral arthritis symptoms persist.
      However, this combination therapy is not effective for the spondylitis symptoms.
      Indeed, AS is one of the rheumatic diseases for which no real disease-modifying
      antirheumatic treatment is available. Challenges in chronic autoimmune arthritis
      have changed dramatically, especially since biotechnological compounds became
      available. These compounds allow for a specific intervention in the immune
      cascade underlying the disease. Tumour necrosis factor (TNF)-alpha antagonists
      (monoclonal antibodies such as infliximab, or soluble receptors such as
      etanercept) are the first representative drugs in this category. Open-label
      studies have shown the efficacy of these new targeted drugs, which has been
      confirmed by controlled studies, at least in the short term. Improvements in
      several clinical parameters, function, quality of life, biological parameters,
      histopathological synovial characteristics and magnetic resonance imaging, have
      all been observed. As a result of these favourable results, anti-TNFalpha therapy
      has been approved for the treatment of AS and should be considered for patients
      with severe axial symptoms and elevated serological markers of inflammatory
      activity who have responded inadequately to conventional nonsteroidal therapy.
      There is evidence that this new therapeutic approach has a disease- and even
      structure-modifying effect in SpA. In this context, structure modification should
      not only be seen as inhibition of bone and cartilage destruction but more broadly
      as modulation of tissue histology. Some questions remain unanswered, such as the
      long-term efficacy and safety of anti-TNFalpha therapy, the extent of structural
      benefit and the cost effectiveness. However, despite these concerns, anti
      TNFalpha therapy represents a major therapeutic advancement in the treatment of
      AS.

PMID- 15563250
TI  - Pregabalin: in the treatment of painful diabetic peripheral neuropathy.
AB  - Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl
      hexanoic acid, has a similar pharmacological profile to that of its developmental
      predecessor gabapentin, but showed greater analgesic activity in rodent models of
      neuropathic pain. The exact mechanism of action of pregabalin is unclear,
      although it may reduce excitatory neurotransmitter release by binding to the
      alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin
      at fixed dosages of 300 and 600 mg/day, administered three times daily, was
      superior to placebo in relieving pain and improving pain-related sleep
      interference in three randomised, double-blind, multicentre studies of 5-8 weeks'
      duration in a total of 724 evaluable patients with painful diabetic peripheral
      neuropathy (DPN). Significant reductions in weekly mean pain scores (primary
      endpoint) and sleep interference scores were observed at 1 week and sustained
      thereafter. A significant reduction in pain was apparent on the first day of
      treatment with pregabalin 300 mg/day. Twice daily fixed (600 mg/day) or flexible
      (150-600 mg/day) pregabalin was also effective in reducing pain and sleep
      interference in two 12-week placebo-controlled trials in a total of 733
      randomised DPN patients. Pregabalin was well tolerated in DPN patients; mild-to
      moderate dizziness, somnolence and peripheral oedema were the most common adverse
      events.

PMID- 15563253
TI  - Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in hepatitis C
      Virus And HIV co-infection.
AB  - Pegylated interferon plus ribavirin is the standard first-line treatment in
      patients with chronic hepatitis C virus (HCV) mono-infection. Although the
      optimal anti-HCV regimen is not established in the more difficult-to-treat
      population with HIV-HCV co-infection, much of the data in this clinical setting
      have been derived from studies evaluating peginterferon-alpha-2a (40kD) [Pegasys]
      plus ribavirin (Copegus), most notably the APRICOT (AIDS Pegasys Ribavirin
      International Co-Infection Trial) and the ACTG (AIDS Clinical Trial Group) A5071
      study. In particular, results of APRICOT - the largest study conducted to date
      with a pegylated interferon plus ribavirin in patients with HIV-HCV co-infection 
      indicate that a substantial proportion of patients will achieve sustained
      virological response (SVR) at week 72 when these drugs are administered for 48
      weeks in an appropriate dosage regimen. In general, the tolerability profile of
      peginterferon-alpha-2a plus ribavirin in APRICOT was similar to that previously
      reported in patients with HCV mono-infection.

PMID- 15563254
TI  - Orlistat: a review of its use in the management of patients with obesity.
AB  - Orlistat is an inhibitor of gastrointestinal lipases and, therefore, prevents the
      absorption of dietary fat. This agent reduces weight in obese adults and
      adolescents with or without comorbidities (including type 2 diabetes mellitus,
      hypercholesterolaemia, hypertension, metabolic syndrome) who received up to 4
      years of therapy in conjunction with a hypocaloric diet. In obese patients,
      orlistat in combination with a hypocaloric diet improved metabolic risk factors
      and reduced the risk of developing type 2 diabetes. Furthermore, this agent was
      cost effective in patients with obesity, particularly those with type 2 diabetes.
      Orlistat is generally well tolerated, with gastrointestinal adverse events being
      most commonly reported. Orlistat, in addition to lifestyle and dietary
      intervention, is thus an attractive option for the treatment of patients with
      obesity, especially those with associated comorbidities or at risk of developing
      type 2 diabetes.

PMID- 15563255
TI  - Predicting motor outcome at preschool age for infants tested at 7, 30, 60, and 90
      days after term age using the Test of Infant Motor Performance.
AB  - BACKGROUND AND PURPOSE: Accurate and diagnostic measures are central to early
      identification and intervention with infants who are at risk for developmental
      delays or disabilities. The purpose of this study was to examine (1) the ability
      of infants' Test of Infant Motor Performance (TIMP) scores at 7, 30, 60 and 90
      days after term age to predict motor development at preschool age and (2) the
      contribution of the home environment and medical risk to the prediction. SUBJECTS
      AND METHODS: Sixty-one children from an original cohort of 90 infants who were
      assessed weekly with the TIMP, between 34 weeks gestational age and 4 months
      after term age, participated in this follow-up study. The Peabody Developmental
      Motor Scales, 2nd edition (PDMS-2), were administered to the children at the mean
      age of 57 months (SD=4.8 months). The quality and quantity of the home
      environment also were assessed at this age using the Early Childhood Home
      Observation for Measurement of the Environment (EC-HOME). Pearson product moment
      correlation coefficients, multiple regression, sensitivity and specificity, and
      positive and negative predictive values were used to assess the relationship
      among the TIMP, HOME, medical risk, and PDMS-2 scores. RESULTS: The correlation
      coefficients between the TIMP and PDMS-2 scores were statistically significant
      for all ages except at 7 days. The highest correlation coefficient was at 90 days
      (r=.69, P=.001). The TIMP scores at 30, 60, and 90 days after term; medical risk
      scores; and EC-HOME scores explained 24%, 23%, and 52% of the variance in the
      PDMS-2 scores, respectively. The TIMP score at 90 days after term was the most
      significant contributor to the prediction. The TIMP cutoff score of -0.5 standard
      deviation below the mean correctly classified 80%, 79%, and 87% of the children
      using a cutoff score of -2 standard deviations on the PDMS-2 at 30, 60, and 90
      days, respectively. DISCUSSION AND CONCLUSION: The results compare favorably with
      those of developmental tests administered to infants at 6 months of age or older.
      These findings underscore the need for age-specific test values and developmental
      surveillance of infants before making referrals.

PMID- 15563256
TI  - Screening for symptoms of depression by physical therapists managing low back
      pain.
AB  - BACKGROUND AND PURPOSE: Depression is a condition that worsens the prognosis of
      low back pain (LBP) and is under-recognized and undertreated in primary care. The
      purpose of this study was to evaluate the accuracy with which physical therapists
      screen for depressive symptoms among their patients with LBP. SUBJECTS: Sixty
      eight physical therapists and 232 patients with nonspecific LBP from 40 physical
      therapy clinics participated. METHODS: Patients completed the reference standard
      (Depression Anxiety Stress Scales [DASS]) and a 2-item screening test for
      depression taken from the Primary Care Evaluation of Mental Disorders Procedure
      (PRIME-MD). Treating physical therapists used a 0 to 10 scale to judge whether
      each patient was depressed. Based on the short-form Depression Anxiety Stress
      Scales (DASS-21) depression scale score, each patient was categorized as
      exhibiting normal, mild, moderate, severe, or extremely severe depression
      symptoms, and receiver operating characteristic (ROC) curves were generated to
      describe test accuracy. RESULTS: The 2-item screening test was more accurate in
      screening for depressive symptoms than the physical therapists' ratings were; for
      example, in detecting moderate depressive symptoms in the 2 areas under the ROC
      curve, values were 0.66 versus 0.79. DISCUSSION AND CONCLUSION: Because the
      therapists did not accurately identify symptoms of depression, even symptoms of
      severe depression, despite the common presentation in their clinics, we recommend
      that physical therapists managing patients with LBP use the 2-item depression
      screening test. Administration of this screening test would improve physical
      therapists' ability to screen for symptoms of depression and would enable
      referral for appropriate management.

PMID- 15563257
TI  - Motor imagery for gait rehabilitation in post-stroke hemiparesis.
AB  - BACKGROUND AND PURPOSE: Reports have described the contribution of motor imagery
      (MI) practice for improving upper-extremity functions in patients with
      hemiparesis following stroke. The purpose of this case report is to describe the
      use of MI practice to attempt to improve walking in an individual with
      hemiparesis. CASE DESCRIPTION: A 69-year-old man with left hemiparesis received
      MI gait practice for 6 weeks. Intervention focused on task-oriented gait and on
      impairments of the affected lower limb. Preintervention, midterm,
      postintervention, and follow-up measurements of temporal-distance stride
      parameters and sagittal kinematics of the knee joint were taken. MAIN OUTCOMES:
      At 6 weeks postintervention, the patient had a 23% increase in gait speed and a
      13% reduction in double-support time. An increase in range of motion of the knees
      also was observed. No changes in gait symmetry were noted. DISCUSSION: The
      outcomes suggest that MI may be useful for the enhancement of walking ability in
      patients following stroke. Because improvement was mainly in temporal-distance
      gait variables and knee movement, imagery practice probably should focus on its
      specific impairments during gait in order to affect the performance of the
      paretic lower extremity.

PMID- 15563258
TI  - Exercise limitation in recipients of lung transplants.

PMID- 15563259
TI  - Evidence underlying breathing retraining in people with stable chronic
      obstructive pulmonary disease.
AB  - The efficacy of pursed-lip breathing (PLB) and diaphragmatic breathing (DB) in
      the rehabilitation of people with chronic obstructive pulmonary disease (COPD)
      remains unclear. This review examines the evidence regarding the usefulness of
      these techniques in improving the breathing of people with stable COPD. The
      studies included in our review of the literature used either PLB or DB in
      isolation, contained a clear description of the methods, and used outcomes that
      were measured with what we considered to be appropriate procedures. Pursed-lip
      breathing slows the respiratory rate, and evidence suggests that this decreases
      the resistive pressure drop across the airways and, therefore, decreases airway
      narrowing during expiration. This decrease in airway narrowing may account for
      the decreased dyspnea some people experience when using this technique.
      Diaphragmatic breathing has negative and positive effects, but the latter appear
      to be caused by simply slowing the respiratory rate. Evidence supports the use of
      PLB, but not DB, for improving the breathing of people with COPD.

PMID- 15563260
TI  - Comparative genomic hybridization analysis for esophageal squamous cell
      carcinoma.

PMID- 15563261
TI  - Recent topics on the surgical treatment for atrial fibrillation.
AB  - After the introduction of endocardial radiofrequency catheter, only two
      arrhythmias, atrial fibrillation and ischemic ventricular tachycardia require
      surgical procedures. In this review, we describe recent advancements and problems
      of surgical treatment for atrial fibrillation. On the basis of multiple-circuit
      re-entry theory, Cox developed the maze operation with the aim of interrupting
      the re-entry circuit. Although this procedure has become the gold standard
      technique for the surgical treatment of atrial fibrillation with approximately
      90% success rate, several modifications have been made over time. To obtain a
      more physiological atrial transport function, radial approach technique or
      bilateral appendage-preserved maze procedures were developed and to simplify
      surgical procedures, maze operation with cryo-ablation or radiofrequency-ablation
      were created. Other topics are concerned with surgical target or approach to
      atrial fibrillation. Ectopic focus theories from pulmonary veins have been widely
      recognized recently and the surgical isolation of pulmonary veins orifices is
      performed with various energy sources. In addition to standard cut-and-sew
      surgical technique, cryoablation, unipolar or bipolar radiofrequency ablation, or
      microwave ablation were induced with endocardial or epicardial approach for the
      achievement of less invasive cardiac surgery. As atrial fibrillation leads to
      frequent mortality, cardiac surgeons have to treat atrial fibrillation with other
      cardiac disease more frequently to obtain better quality of operative results.

PMID- 15563262
TI  - Pre- and post-operative serum carcinoembryonic antigen in primary lung
      adenocarcinoma.
AB  - The clinical value of pre- and post-operative serum carcinoembryonic antigen
      (CEA) concentration (mean +/- SEM, ng/ml) in surgically treated primary lung
      cancer patients with adenocarcinoma (n=97) was studied. Preoperative CEA in pT2
      patients (18.3+/-8.0) was higher than in pT1 (10.5+/-6.4, p<0.05) but was not
      different from pT3 patients (19.7+/-6.7). Preoperative CEA in pN1 patients (5.9+/
      1.6) was lower than in pN2 (28.2+/-13.2, p<0.05) but not different from pN0
      patients (8.8+/-3.8); p-stage II patients (8.2+/-4.7) had lower values than p
      stage III patients (26.7+/-10.5, p<0.05), but not p-stage I patients (7.9+/-3.9).
      The CEA was not different between p-stages IA and IIA (3.5+/-0.6, 6.1+/-3.2) and
      IB and IIB (17.0+/-11.8, 11.7+/-7.8), but was different between IA and IB
      (p<0.05) and IIA and IIB (p<0.05). Preoperative CEA did not differ between
      patients who received complete (12.7+/-4.7) versus incomplete (9.5+/-6.0)
      resections, nor between patients who developed recurrence after surgery (21.9+/
      10.4) versus those who were disease-free (30.9+/-21.7). CEA obtained 2 months
      after surgery in patients who recurred or metastasized after surgery (63.1+/
      47.0) was higher than in disease-free patients (4.8+/-1.6, p<0.05). The post-/pre
      operative CEA ratio in patients who recurred or metastasized after surgery
      (146.6+/-53.3%) was also higher than in disease-free patients (91.0+/-10.9%,
      p=0.05). In conclusion, CEA reflected tumor size but not the tumor invasion nor
      hilar lymph node disease; patients with mediastinal lymph node involvement had
      higher CEA values. Preoperative CEA did not reflect the likelihood of complete
      resection nor postoperative metastasis, but postoperative CEA obtained 2 months
      after surgery did reflect postoperative metastasis.

PMID- 15563263
TI  - Hemodynamics during humoral rejection events with total versus standard
      orthotopic heart transplantation.
AB  - PURPOSE: We hypothesized that total orthotopic heart transplantation (TOHT)
      improves humoral rejection hemodynamics compared with biatrial transplantation or
      standard orthotopic heart transplantation (SOHT). METHODS: We reviewed 1942
      biopsies from 134 patients (pts) and right heart catheterization data obtained at
      endomyocardial biopsy. Biopsies that displayed humoral rejection by histological
      findings and positive immunofluorescence for immunoglobulins and complement were
      analyzed. Patients with pacemakers, atrial fibrillation or beta-blocker therapy
      at the time of biopsy were excluded. Thirty-two pts after TOHT and 22 after SOHT
      matching these criteria were identified. RESULTS: Demographic data, underlying
      disease, pretransplant hemodynamics, and donor demographics were similar. Cardiac
      output and index were higher in the total orthotopic group (5.9+/-1.1 vs 5.1+/
      1.4 L/min, p=0.027; 3.3+/-0.5 vs 2.8+/-0.6 L/min/m2, p=0.016). Right atrial and
      pulmonary capillary wedge pressure were lower after TOHT (7+/-3 vs 11+/-5 mmHg,
      p<0.001; 13+/-4 vs 16+/-5 mmHg, p=0.035). Pulmonary pressures, pulmonary vascular
      resistance and heart rate were similar. CONCLUSION: TOHT offers improved
      hemodynamics during humoral rejection as evidenced by higher cardiac output and
      index with lower right atrial and pulmonary capillary wedge pressures. Future
      studies must examine the potential benefits of TOHT during combined cellular and
      humoral rejection events.

PMID- 15563264
TI  - Intrapulmonary cystic benign teratoma: a case report and review of the
      literature.
AB  - We describe a 41-year-old woman with a short history of retrosternal chest pain
      and non-productive cough due to a benign intrapulmonary teratoma originating from
      the left upper lobe. The clinical, CT features of this rare tumor are presented
      and the relevant literature is discussed.

PMID- 15563265
TI  - Dramatic improvement of respiratory condition after lobectomy for localized
      bullous emphysema.
AB  - A case of dramatic improvement of respiratory function after lobectomy for
      bullous emphysema with severe hyperinflation of the left lower lobe was reported.
      A 72-year-old gentleman was admitted to our hospital due to increasing dyspnea
      with Hugh-Johns class V. His chest X-ray and computed tomography revealed a
      hyperinflation of the left lower lobe. Despite medication and respiratory
      rehabilitation, blood gas analysis showed hypercapnia and his symptoms had been
      progressing. Bronchofiberscopy revealed that the left lower lobe bronchi opened
      on inspiration and closed on expiration. Since complete destruction of the lower
      lobe due to air trapping was thought to be the cause of localized hyperinflation
      and the compression of left upper lobe, left lower lobectomy was performed. His
      dyspnea immediately disappeared and the respiratory function improved
      dramatically. We concluded that lobectomy could be considered as one of surgical
      options in case of complete lobar destruction in emphysema patients.

PMID- 15563266
TI  - Primary malignant lymphoma arising in the pleura without preceding long-standing
      pyothorax.
AB  - We report a very rare case of primary malignant lymphoma arising in the pleura
      with no history of persistent pyothorax. A 72-year-old male was hospitalized with
      dyspnea on effort and chest CT demonstrated a mass along the right chest wall.
      Right thoracotomy with complete en bloc resection of the pleural tumor was
      performed. Immunohistochemical examination of the pleural tumor showed that the
      histology was marginal zone B-cell malignant lymphoma. We considered that this
      tumor had originated from the soft tissue in the chest wall based on
      radiographical and surgical findings. As diagnosis and treatment of pleural
      malignant lymphoma seems to have been difficult in most cases reported in the
      literature, it is thought that early active and accurate biopsy with large-bore
      needles, or, if possible, surgical incision for early diagnosis and aggressive
      surgery to achieve complete resection combined with radiation therapy and/or
      chemotherapy would be very important for a good prognosis.

PMID- 15563267
TI  - New material for Nuss procedure.
AB  - The Nuss procedure for pectus excavatum repair has been considered an acceptable
      method in terms of its decreased invasiveness and excellent cosmetic results.
      Although a steel bar is usually used for elevating the sternum, we used a
      titanium alloy plate for pectus excavatum repair for the first time. The
      characteristics of this plate are that 1) it comes out translucently on X-rays,
      2) MRI examination is possible because titanium will not be magnetized, and 3) it
      is possible to go through the security checkpoint at the airport without setting
      off the metal detector. Furthermore, the titanium alloy is highly elastic, which
      reduces complications such as dislocation, and it excels in the conformity to
      organization. Patients who have received the Nuss operation are forced to
      somewhat limit their daily life for two or three years until the bar is removed.
      A plate made from titanium alloy resolves this problem because of its material
      and it is thought to be an ideal candidate for elevating the sternum during the
      Nuss operation.

PMID- 15563268
TI  - Open heart surgery in a paraplegic patient.
AB  - We operated on a patient who had been paraplegic since sustaining a spinal cord
      injury 11 years ago. We made a reversed L-shaped sternum incision and cannulated
      all tubes for the cardiopulmonary bypass through a wound window. This provided an
      excellent surgical view without restricting the patient's upper limbs (needed for
      wheel chair operation), and recovery was good. Just after surgery, however, it
      was difficult to control blood pressure and the loss of serum albumin. We believe
      this is the first report of open-heart surgery undertaken in a paraplegic patient
      and that the reversed L-shaped incision and careful monitoring of hemodynamics
      each played an important role in the successful outcome. We hope that this report
      will help in the treatment of other paraplegic patients who need open-heart
      surgery.

PMID- 15563269
TI  - Partial left ventriculectomy for end-stage cardiomyopathy: report of a case.
AB  - Cardiac transplantation is an established treatment for end-stage heart failure,
      but its use is very limited. Partial left ventriculectomy has been reported as an
      alternative treatment for end-stage dilated cardiomyopathy. However, it has been
      well recognized that emergency partial left ventriculectomy for intractable
      decompensation is associated with poor survival. We report a case of a 68-year
      old man with a left ventricular end-diastolic diameter of 108 mm, who underwent
      emergency extended partial left ventriculectomy, without papillary muscle
      resection, and mitral valve replacement with chordae preservation to deal with
      ongoing cardiogenic shock caused by end-stage dilated cardiomyopathy. The
      patient's cardiac status and general condition improved after the operation, and
      he survived the crisis. This operation should be considered as an alternative
      strategy for patients with septal motion and very large left ventricle. Thus, we
      report a successful extended partial left ventriculectomy and mitral valve
      replacement for end-stage dilated cardiomyopathy with very large left ventricular
      end-diastolic diameter.

PMID- 15563270
TI  - Coronary artery bypass grafting and aortic valve replacement in a patient with a
      tracheostoma.
AB  - We report a 67-year-old man with a tracheostoma who successfully underwent
      coronary artery bypass grafting and aortic valve replacement. He had received
      both a tracheostoma just above the sternal notch after total laryngectomy. As the
      standard full sternotomy might cause mediastinitis, we performed the operation
      through a lower half sternotomy with a limited skin incision. Postoperatively the
      wound was covered with a sterile plastic drape to prevent infection from the
      tracheostoma. The postoperative course was uneventful.

PMID- 15563271
TI  - Mycotic aneurysm of the descending aorta with hemoptysis.
AB  - Mycotic aneurysm of the descending aorta is usually described as rare. We present
      two recent cases of mycotic aneurysm of the descending aorta complicated with
      hemoptysis. Urgent tube graft replacements were successfully performed under
      cardiopulmonary bypass support. Bacterial causes of the aneurysms were
      methicillin-resistant Staphylococcus aureus in the first case and Staphylococcus
      aureus in the second case. Although the first patient died fifteenth months after
      surgery, the second patient remains well fourteenth months after the operation.

PMID- 15563272
TI  - A true aneurysm of the posterior tibial artery: a case report.
AB  - True aneurysm of the posterior tibial artery is very rare. A 69-year-old woman
      presented with a pulsatile painful mass of the right lower leg.

PMID- 15563273
TI  - Regulation of reactive oxygen species (ROS) production by C18 fatty acids in
      Jurkat and Raji cells.
AB  - In the present study, the effects of C18 fatty acids with different numbers of
      double bonds, SA (stearic acid; C18:0), OA (oleic acid; C18:1), LA (linoleic
      acid; C18:2) and gamma-LNA (gamma-linolenic acid; C18:3), on ROS (reactive oxygen
      species) production by Jurkat (a human T-lymphocyte-derived cell line) and Raji
      (a human B-lymphocyte-derived cell line) cells were investigated. ROS production
      was determined by NBT (Nitro Blue Tetrazolium) reduction (intracellular and
      extracellular ROS production) and by dihydroethidium oxidation using flow
      cytometry (intracellular ROS production). The effectiveness on ROS production was
      gamma-LNA<SA<OA<LA in Jurkat cells and SA<gamma-LNA<OA<LA in Raji cells. LA
      (found in corn, soya bean and sunflower oils) was more potent than OA (found in
      olive oil) in stimulating ROS production in both Raji and Jurkat cells. The lower
      ROS production by OA compared with LA may be one of the benefits of olive oil
      consumption. As SA and gamma-LNA acids had little or no effect, further studies
      on the site of ROS production in these cells were carried out with OA and LA
      only. Activation of NADPH oxidase via PKC (protein kinase C) was found to be the
      major mechanism of ROS production induced by OA and LA in Jurkat and Raji cells.

PMID- 15563274
TI  - Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family,
      implicated in adipocyte maturation and development of obesity.
AB  - Few cell adhesion molecules have been reported to be expressed in mature
      adipocytes, and the significance of cell adhesion process in adipocyte biology is
      also unknown. In the present study, we identified ACAM (adipocyte adhesion
      molecule), a novel homologue of the CTX (cortical thymocyte marker in Xenopus)
      gene family. ACAM cDNA was isolated during PCR-based cDNA subtraction, and its
      mRNA was shown to be up-regulated in WATs (white adipose tissues) of OLETF
      (Otsuka Long-Evans Tokushima fatty) rats, an animal model for Type II diabetes
      and obesity. ACAM, 372 amino acids in total, has a signal peptide, V-type
      (variable) and C2-type (constant) Ig domains, a single transmembrane segment and
      a cytoplasmic tail. The amino acid sequence in rat is highly homologous to mouse
      (94%) and human (87%). ACAM mRNA was predominantly expressed in WATs in OLETF
      rats, and increased with the development of obesity until 30 weeks of age, which
      is when the peak of body mass is reached. Western blot analysis revealed that
      ACAM protein, approx. 45 kDa, was associated with plasma membrane fractions of
      mature adipocytes isolated from mesenteric and subdermal adipose deposits of
      OLETF rats. Up-regulation of ACAM mRNAs in obesity was also shown in WATs of
      genetically obese db/db mice, diet-induced obese ICR mice and human obese
      subjects. In primary cultured mouse and human adipocytes, ACAM mRNA expression
      was progressively up-regulated during differentiation. Several stably transfected
      Chinese-hamster ovary K1 cell lines were established, and the quantification of
      ACAM mRNA and cell aggregation assay revealed that the degree of homophilic
      aggregation correlated well with ACAM mRNA expression. In summary, ACAM may be
      the critical adhesion molecule in adipocyte differentiation and development of
      obesity.

PMID- 15563275
TI  - Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene:
      identification of a functional hypoxia-responsive element.
AB  - The HIFs (hypoxia-inducible factors) are a family of heterodimeric transcription
      factors essential for the adaptation of cells to reduced oxygen supply. Three
      human PHDs (prolyl hydroxylase domain proteins, PHD1-PHD3) initiate oxygen
      dependent degradation of HIF-alpha-subunits in normoxia. RNA interference
      directed against PHD2, but not PHD1 or PHD3, is sufficient to stabilize HIF
      1alpha in normoxia. Therefore PHD2 is regarded as the main cellular oxygen
      sensor. PHD2 itself is up-regulated by hypoxia and may thus limit hypoxic
      signalling. By sequence analysis, we predicted a promoter approx. 3.5 kb 5' of
      the translation start codon and a second promoter located in a CpG island
      immediately upstream of the coding sequence. A consensus HIF-1-binding site that
      is conserved in the murine phd2 gene was detected in the CpG island. By
      electrophoretic mobility-shift assay, we demonstrated binding of HIF-1 to the
      putative HIF-1-binding site. In luciferase reporter vectors, the isolated
      upstream promoter was inactive in all cell lines tested unless 200 bp were
      deleted at the 3'-end. The downstream promoter was active and induced by hypoxia.
      In reporter vectors containing both promoter sequences, luciferase activity was
      equal to vectors containing only the downstream promoter. In cells transfected
      with a vector containing both promoters, a single luciferase transcript was
      detectable. This transcript had the same length as transcripts from a vector
      containing the downstream promoter only. We conclude that the phd2 gene is
      transcribed exclusively from the downstream promoter that contains a functional
      hypoxia-responsive, cis-regulatory element. Our results establish that PHD2 is a
      direct HIF target gene.

PMID- 15563276
TI  - Mucin glycosylation changes in cystic fibrosis lung disease are not manifest in
      submucosal gland secretions.
AB  - SMG (submucosal gland) secretions are a major component of the airway surface
      liquid, are associated with innate immunity in the lung, and have been reported
      to be altered in lung disease. Changes in lung mucosal glycosylation have been
      reported in CF (cystic fibrosis), which may be responsible for differential
      bacterial binding to glycosylated components in the lung mucosa and hence
      increased pre-disposition to pulmonary infection. Glycoproteomic analysis was
      performed on SMG secretions collected from explanted bronchial tissue of subjects
      with severe lung disease, with and without CF, and controls without lung disease.
      Mucins MUC5B and MUC5AC were shown to be the dominant high-molecular-mass
      glycoprotein components, with a minor non-mucin glycoprotein component, gp-340,
      also present. Oligosaccharides containing blood-group determinants corresponding
      to subjects' blood type were abundant on MUC5B/MUC5AC, as were Lewis-type
      epitopes and their sialylated analogues, which are ligands for pathogens and
      leucocytes. No significant differences were found in the glycosylation of
      MUC5B/MUC5AC or gp-340 between CF and non-CF subjects with severe lung disease,
      implying that CF does not influence SMG secretion mucin glycosylation in end
      stage lung disease. There were also no significant differences found in the
      glycosylation of these components in severe lung disease compared with non
      diseased lungs. This suggests that previously reported changes in the
      glycosylation of respiratory glycoconjugates in CF, and other pulmonary
      conditions, are not due to the glycosylation of components in SMG secretions, but
      may involve other secretions, responses or extracellular factors.

PMID- 15563277
TI  - Bounding poorly characterized risks: a lung cancer example.
AB  - For diseases with more than one risk factor, the sum of probabilistic estimates
      of the number of cases caused by each individual factor may exceed the total
      number of cases observed, especially when uncertainties about exposure and dose
      response for some risk factors are high. In this study, we outline a method of
      bounding the fraction of lung cancer fatalities not due to specific well-studied
      causes. Such information serves as a "reality check" for estimates of the impacts
      of the minor risk factors, and, as such, complements the traditional risk
      analysis. With lung cancer as our example, we allocate portions of the observed
      lung cancer mortality to known causes (such as smoking, residential radon, and
      asbestos fibers) and describe the uncertainty surrounding those estimates. The
      interactions among the risk factors are also quantified, to the extent possible.
      We then infer an upper bound on the residual mortality due to "other" causes,
      using a consistency constraint on the total number of deaths, the maximum
      uncertainty principle, and the mathematics originally developed of imprecise
      probabilities.

PMID- 15563278
TI  - Bounding analysis as an inadequately specified methodology.
AB  - The bounding analysis methodology described by Ha-Duong et al. (this issue) is
      logically incomplete and invites serious misuse and misinterpretation, as their
      own example and interpretation illustrate. A key issue is the extent to which
      these problems are inherent in their methodology, and resolvable by a logically
      complete assessment (such as Monte Carlo or Bayesian risk assessment), as opposed
      to being general problems in any risk-assessment methodology. I here attempt to
      apportion the problems between those inherent in the proposed bounding analysis
      and those that are more general, such as reliance on questionable expert
      elicitations. I conclude that the specific methodology of Ha-Duong et al. suffers
      from logical gaps in the definition and construction of inputs, and hence should
      not be used in the form proposed. Furthermore, the labor required to do a sound
      bounding analysis is great enough so that one may as well skip that analysis and
      carry out a more logically complete probabilistic analysis, one that will better
      inform the consumer of the appropriate level uncertainty. If analysts insist on
      carrying out a bounding analysis in place of more thorough assessments, extensive
      analyses of sensitivity to inputs and assumptions will be essential to display
      uncertainties, arguably more essential than it would be in full probabilistic
      analyses.

PMID- 15563280
TI  - Bacon, Boole, and Popper.

PMID- 15563281
TI  - Hexavalent chromium and lung cancer in the chromate industry: a quantitative risk
      assessment.
AB  - The purpose of this investigation was to estimate excess lifetime risk of lung
      cancer death resulting from occupational exposure to hexavalent-chromium
      containing dusts and mists. The mortality experience in a previously studied
      cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths
      was analyzed with Poisson regression methods. Extensive records of air samples
      evaluated for water-soluble total hexavalent chromium were available for the
      entire employment history of this cohort. Six different models of exposure
      response for hexavalent chromium were evaluated by comparing deviances and
      inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at
      hire was included in the model. Lifetime risks of lung cancer death from exposure
      to hexavalent chromium (assuming up to 45 years of exposure) were estimated using
      an actuarial calculation that accounts for competing causes of death. A linear
      relative rate model gave a good and readily interpretable fit to the data. The
      estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium
      (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess
      lifetime risk of lung cancer death from exposure to hexavalent chromium at the
      current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be
      255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous
      estimates by U.S. EPA, California EPA, and OSHA using different occupational
      data. Our analysis predicts that current occupational standards for hexavalent
      chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in
      10, which is consistent with previous risk assessments.

PMID- 15563282
TI  - Combined effects of contaminant desorption and toxicity on risk from PAH
      contaminated sediments.
AB  - A strong inverse correlation was observed between the polycyclic aromatic
      hydrocarbon (PAH) mass fraction desorbed, a surrogate measure of bioavailability,
      and relative carcinogenicity, as quantified by potency equivalency factors
      (PEFs), for two study sediments from the New York/New Jersey Harbor estuary.
      Because compounds with the highest toxicity, such as dibenz(a,h)anthracene and
      benzo(a)pyrene (BAP), also tended to be the least rapidly and least extensively
      desorbed, the U.S. Environmental Protection Agency (EPA) default guidance may
      dramatically overestimate risk from exposure to PAH-contaminated soils or
      sediments. A "relative risk index" (RRI) was developed to account for the
      combined effects of compound-specific bioavailability and toxic potency in
      estimating excess cancer risk. Using this approach, estimated excess cancer risk
      may be diminished by as much as a factor of 159 times versus default EPA
      guidance. Also, the hierarchy of estimated risk between study sediments and among
      treatment fractions of study sediments differed using the two approaches,
      implying that the default approach may inaccurately determine site clean-up
      priorities. The percentage contribution of each potentially carcinogenic priority
      PAH to total excess cancer risk was computed under various scenarios. In each
      case, the contribution of BAP to total excess cancer risk was remarkably
      invariable, for example, ranging from 48% to 52% in one sediment, and 44% to 54%
      in the other, over four different exposure durations. These results suggest that
      BAP may be an excellent indexing compound for gauging relative exposure risk
      across sediments. Other important contributors to total excess cancer risk were
      benz(a)anthracene and dibenz(a,h)anthracene. Together, these three compounds
      comprised nearly 90% of total excess cancer risk from all PAHs in every scenario.
      This integrated RRI approach may enable regulators to more accurately gauge
      relative risks and make more informed sediment management decisions.

PMID- 15563283
TI  - Pathway analysis for population-total health impacts of toxic metal emissions.
AB  - This article describes a simple model for quantifying the health impacts of toxic
      metal emissions. In contrast to most traditional models it calculates the
      expectation value of the total damage (summed over the total population and over
      all time) for typical emission sites, rather than "worst-case" estimates for
      specific sites or episodes. Such a model is needed for the evaluation of many
      environmental policy measures, e.g., the optimal level of pollution taxes or
      emission limits. Based on the methodology that has been developed by USEPA for
      the assessment of multimedia pathways, the equations and parameters are assembled
      for the assessment of As, Cd, Cr, Hg, Ni, and Pb, and some typical results are
      presented (the dose from seafood is not included and for Hg the results are
      extremely uncertain); the model is freely available on the web. The structure of
      the model is very simple because, as we show, if the parameters can be
      approximated by time-independent constants (the case for the USEPA methodology),
      the total impacts can be calculated with steady-state models even though the
      environment is never in steady state. The collective ingestion dose is found to
      be roughly 2 orders of magnitude larger than the collective dose via inhalation.
      The uncertainties are large, easily an order of magnitude, the main uncertainties
      arising from the parameter values of the model, in particular the transfer
      factors. Using linearized dose-response functions, estimates are provided for
      cancers due to As, Cd, Cr, and Ni as well as IQ loss due to Pb emissions in
      Europe.

PMID- 15563284
TI  - The maximally exposed individual--comparison of maximum likelihood estimation of
      high quantiles to an extreme value estimate.
AB  - The dose to human and nonhuman individuals inflicted by anthropogenic radiation
      is an important issue in international and domestic policy. The current paradigm
      for nonhuman populations asserts that if the dose to the maximally exposed
      individuals in a population is below a certain criterion (e.g., <10 mGy d(-1))
      then the population is adequately protected. Currently, there is no consensus in
      the regulatory community as to the best statistical approach. Statistics,
      currently considered, include the maximum likelihood estimator for the 95th
      percentile of the sample mean and the sample maximum. Recently, the investigators
      have proposed the use of the maximum likelihood estimate of a very high quantile
      as an estimate of dose to the maximally exposed individual. In this study, we
      compare all of the above-mentioned statistics to an estimate based on extreme
      value theory. To determine and compare the bias and variance of these statistics,
      we use Monte Carlo simulation techniques, in a procedure similar to a parametric
      bootstrap. Our results show that a statistic based on extreme value theory has
      the least bias of those considered here, but requires reliable estimates of the
      population size. We recommend establishing the criterion based on what would be
      considered acceptable if only a small percentage of the population exceeded the
      limit, and hence recommend using the maximum likelihood estimator of a high
      quantile in the case that reliable estimates of the population size are not
      available.

PMID- 15563285
TI  - Bayesian Monte Carlo uncertainty analysis of human health risks from animal
      antimicrobial use in a dynamic model of emerging resistance.
AB  - Recent qualitative analyses warn of potential future human health risks from
      emergence of antibiotic resistance in food-borne pathogens due to the use of
      similar antimicrobial drugs in both food animals and human medicine. While
      historical data suggest that human health risks from some animal antimicrobials,
      such as virginiamycin (VM), have remained low (McDonald et al., 2001), there is a
      widespread concern that "resistance epidemics" or endemics could arise in the
      future. How reassuring is the past about the future? This article applies
      quantitative risk assessment methods to help find out, using human health risks
      from VM and the nearly identical human antimicrobial quinupristin-dalfopristin
      (QD) as a case study. A dynamic simulation model is used to predict the risks of
      emerging resistance to human antimicrobials in human populations from given input
      assumptions. Bayesian Monte Carlo uncertainty analysis allows past data to
      constrain and inform selection of input parameter values, and thus to predict the
      possible future resistance patterns that are consistent with historical data. The
      results show that health risks from VM use in food animals are highly sensitive
      to the human prescription rate of QD. For realistic prescription rates,
      quantitative risks are less than 1 x 10(-6) even for members of the most
      threatened (ICU patient) population, while societal risks are <1 excess
      statistical death per year for the whole U.S. population. Such quantitative
      estimates complement more qualitative assessments that discuss the possibility of
      future "resistance epidemics" (or endemics) without quantifying their
      probabilities.

PMID- 15563286
TI  - Addressing nonlinearity in the exposure-response relationship for a genotoxic
      carcinogen: cancer potency estimates for ethylene oxide.
AB  - Ethylene oxide (EO) has been identified as a carcinogen in laboratory animals.
      Although the precise mechanism of action is not known, tumors in animals exposed
      to EO are presumed to result from its genotoxicity. The overall weight of
      evidence for carcinogenicity from a large body of epidemiological data in the
      published literature remains limited. There is some evidence for an association
      between EO exposure and lympho/hematopoietic cancer mortality. Of these cancers,
      the evidence provided by two large cohorts with the longest follow-up is most
      consistent for leukemia. Together with what is known about human leukemia and EO
      at the molecular level, there is a body of evidence that supports a plausible
      mode of action for EO as a potential leukemogen. Based on a consideration of the
      mode of action, the events leading from EO exposure to the development of
      leukemia (and therefore risk) are expected to be proportional to the square of
      the dose. In support of this hypothesis, a quadratic dose-response model provided
      the best overall fit to the epidemiology data in the range of observation. Cancer
      dose-response assessments based on human and animal data are presented using
      three different assumptions for extrapolating to low doses: (1) risk is linearly
      proportionate to dose; (2) there is no appreciable risk at low doses (margin-of
      exposure or reference dose approach); and (3) risk below the point of departure
      continues to be proportionate to the square of the dose. The weight of evidence
      for EO supports the use of a nonlinear assessment. Therefore, exposures to
      concentrations below 37 microg/m3 are not likely to pose an appreciable risk of
      leukemia in human populations. However, if quantitative estimates of risk at low
      doses are desired and the mode of action for EO is considered, these risks are
      best quantified using the quadratic estimates of cancer potency, which are
      approximately 3.2- to 32-fold lower, using alternative points of departure, than
      the linear estimates of cancer potency for EO. An approach is described for
      linking the selection of an appropriate point of departure to the confidence in
      the proposed mode of action. Despite high confidence in the proposed mode of
      action, a small linear component for the dose-response relationship at low
      concentrations cannot be ruled out conclusively. Accordingly, a unit risk value
      of 4.5 x 10(-8) (microg/m3)(-1) was derived for EO, with a range of unit risk
      values of 1.4 x 10(-8) to 1.4 x 10(-7) (microg/m3)(-1) reflecting the uncertainty
      associated with a theoretical linear term at low concentrations.

PMID- 15563287
TI  - Standardized approach for developing probabilistic exposure factor distributions.
AB  - The effectiveness of a probabilistic risk assessment (PRA) depends on the quality
      and relevance of the output from exposure and risk models, which, in turn,
      depends on the critical inputs to the assessment. These critical inputs are often
      in the form of probabilistic exposure factor distributions that are derived for
      the given risk scenario. Deriving probabilistic distributions for model inputs
      can be time consuming and subjective. The absence of a standard approach for
      developing these distributions can result in PRAs that are inconsistent and
      difficult to review by regulatory agencies. We present an approach that reduces
      subjectivity in the distribution development process without limiting the
      flexibility needed to prepare relevant PRAs. The approach requires two steps.
      First, we analyze data pooled at a population scale to (i) identify the most
      robust demographic descriptors within the population for a given exposure factor,
      (ii) partition the data into subsets based on these variables, and (iii)
      construct archetypal distributions for each subpopulation. Second, we sample from
      these archetypal distributions according to site- or scenario-specific conditions
      to simulate exposure factor values and use these values to construct the scenario
      specific input distribution. The archetypal distributions developed through Step
      1 provide a consistent basis for developing scenario-specific distributions so
      risk assessors will not have to repeatedly collect and analyze raw data for each
      new assessment. We demonstrate the approach for two commonly used exposure
      factors--body weight (BW) and exposure duration (ED)--using data that are
      representative of the U.S. population. For these factors we provide a first set
      of subpopulation-based archetypal distributions and demonstrate methods for using
      these distributions to construct relevant scenario-specific probabilistic
      exposure factor distributions.

PMID- 15563288
TI  - Worker exposure standard for phosphine gas.
AB  - The 1998 U.S. Environmental Protection Agency Office of Pesticide Programs (OPP)
      re-registration eligibility decision (RED) for phosphine fumigants has generated
      much interest in defining safe levels of exposure for workers and worker
      bystanders. This report summarizes the pertinent literature on phosphine
      toxicity, including animal inhalation studies and human epidemiology studies, and
      also describes a margin-of-exposure (MOE) analysis based on available worker
      exposure data. In addition, a safe occupational exposure limit is estimated using
      typical OPP assumptions, after determination of appropriate uncertainty factors,
      based on quality of data in the principal study and pharmacokinetic
      considerations. While a conservative 8-hour time-weighted average (TWA) of 0.1
      ppm was calculated, the overall weight of evidence, from a risk-management
      perspective, supports a conclusion that an occupational TWA of 0.3 ppm provides
      adequate health protection. In addition, a 15-minute short-term exposure limit
      (STEL) of 3 ppm was estimated. Finally, in contrast to the MOE analysis described
      in the OPP's phosphine RED, the MOE analysis described herein does not indicate
      that fumigation workers are currently being exposed to unacceptable levels of
      phosphine. Collectively, these findings support the occupational exposure limits
      of 0.3 ppm (8-hour TWA) and 1 ppm (STEL) established in the updated applicator's
      manuals for phosphine-generating products, which recently received approval from
      OPP.

PMID- 15563289
TI  - Risk management for Leontief-based interdependent systems.
AB  - When stricken by a terrorist attack, a war, or a natural disaster, an economic
      unit or a critical infrastructure may suffer significant loss of productivity.
      More importantly, due to interdependency or interconnectedness, this initial loss
      may propagate into other systems and eventually lead to much greater derivative
      loss. This belongs to what is known as a cascading effect. It is demonstrated in
      this article that the cascading effect and the derivative loss can be
      significantly reduced by effective risk management. This is accomplished by
      deliberately distributing the initial inoperability to other systems so that the
      total loss (or inoperability) is minimized. The optimal distribution strategy is
      found by a linear programming technique. The same risk management can also be
      applied to situations where objectives need to be prioritized. A case study
      featuring 12 economic sectors illustrates the theory. The result suggests that
      using the same amount of resources, minimizing risk (inoperability) of
      infrastructures will generally give rise to highest payoff, whereas overlooking
      it may result in greatest total loss. The framework developed in this work uses a
      steady-state approach that applies primarily to managing situations where the
      attack is catastrophic resulting in very long recovery time.

PMID- 15563290
TI  - Spatial risk assessment across large landscapes with varied land use: lessons
      from a conservation assessment of military lands.
AB  - Spatial decision-support tools are necessary for assessment and management of
      threats to biodiversity, which in turn is necessary for biodiversity
      conservation. In conjunction with the U.S. Geological Survey-Biological Resources
      Division's Species at Risk program, we developed a GIS-based spatial decision
      support tool for relative risk assessments of threats to biodiversity on the U.S.
      Army's White Sands Missile Range and Fort Bliss (New Mexico and Texas) due to
      land uses associated with military missions of the two bases. The project tested
      use of spatial habitat models, land-use scenarios, and species-specific impacts
      to produce an assessment of relative risks for use in conservation planning on
      the 1.2 million-hectare study region. Our procedure allows spatially explicit
      analyses of risks to multiple species from multiple sources by identifying a set
      of hazards faced by all species of interest, identifying a set of feasible
      management alternatives, assigning scores to each species for each hazard, and
      mapping the distribution of these hazard scores across the region of interest for
      each combination of species/management alternatives. We illustrate the procedure
      with examples. We demonstrate that our risk-based approach to conservation
      planning can provide resource managers with a useful tool for spatial assessment
      of threats to species of concern.

PMID- 15563291
TI  - Role of comparative risk assessment in addressing environmental security in the
      middle East.
AB  - During the 21st century, environmental challenges are likely to intensify across
      the world and possibly lead to violent conflicts. Strategies for conflict
      avoidance will be incomplete unless they recognize, discuss, and mitigate
      regional environmental stress factors. Comparative risk assessment (CRA) is one
      of the most critical tools emerging to influence modern environmental policies
      and is increasingly used to create a common language to help reconcile competing
      interests in development and environmental disputes around the world. This
      article considers the environmental challenges facing the Middle East in light of
      their "transboundary" nature and proposes CRA as a framework for setting
      environmental priorities and reducing tensions in the region.

PMID- 15563292
TI  - Some Bayesian experimental design theory for risk reduction in extrapolation.
AB  - Decision problems depending on extrapolation promise to become increasingly
      important. The key problem is determining if the model being used for
      extrapolation is going to give reasonable results, or err in a dangerous manner.
      Ideally, as one proceeds from investigation to decision, some guidance should be
      present based on the goal as to which investigation will reduce the risk the most
      given the cost. In this report, a very simple version of the problem is
      formalized and examined. The result is, interestingly, that the best evidence in
      support of the favored model is a null result in the experiment most likely to
      raise doubt over that model. The theory is applied to a simple example drawn from
      accelerated testing.

PMID- 15563293
TI  - AGAPE-ET: a methodology for human error analysis of emergency tasks.
AB  - This article introduces a human error analysis or human reliability analysis
      methodology, AGAPE-ET (A Guidance And Procedure for Human Error Analysis for
      Emergency Tasks), for analyzing emergency tasks in nuclear power plants. The
      AGAPE-ET method is based on a simplified cognitive model and a set of performance
      influencing factors (PIFs). At each cognitive function, error-causing factors
      (ECF) or error-likely situations have been identified considering the
      characteristics of the performance of each cognitive function and the influencing
      mechanism of the PIFs on the cognitive function. Then, a human error analysis
      procedure based on the error analysis factors is organized to cue or guide the
      analyst in conducting the human error analysis. The method can be characterized
      by the structured identification of weak points of the task required to be
      performed and by the efficient analysis process such that the analyst has only to
      carry out the analysis with the necessary cognitive functions. Through the
      application, AGAPE-ET showed its usefulness, which effectively identifies the
      vulnerabilities with respect to cognitive performance as well as task execution,
      and that helps the analyst directly draw specific error reduction measures
      through the analysis.

PMID- 15563294
TI  - Arguments for testing ethnic identity and acculturation as factors in risk
      judgments.
AB  - Understanding of risk views in multiethnic societies and in a globalizing world
      may be enhanced by use of measures of ethnic identity and acculturation. Ethnic
      identity includes such attributes as positive attitudes about one's ethnic group
      and a sense of belonging to it, voluntary and frequent association with other
      ethnic group members, and ethnic practices (preferred music, food, language;
      attendance at ethnic festivities). Acculturation is absorption of the "host"
      society's cultural norms, beliefs, attitudes and behavior patterns by immigrants,
      or by other groups historically excluded from the larger society. Both generic
      and ethnicity-specific measures of these concepts are available in the
      literature. This Perspective reviews the literature on risk implications of these
      concepts, how the nature of these measures presents both opportunities and
      challenges to risk researchers, and the degree to which ethnic identity and
      acculturation may be correlated with sociodemographic factors. Conceptual and
      methodological suggestions are made for risk research using these concepts, and
      hypotheses are offered about what such research might find.

PMID- 15563295
TI  - Expert and public perception of risk from biotechnology.
AB  - Risk perceptions of a series of biotechnology applications were examined in a
      public (nonexpert) sample and an expert sample. Compared with the experts, the
      public perceived all biotechnology applications as more risky. Both groups
      perceived food-related applications to be riskier than medical applications.
      Compared with the public, experts perceived both food and medical applications as
      less harmful and more useful. Experts also judged the risks posed from medical
      biotechnology applications as more familiar and acknowledged by people and
      science. Lay estimates of the risk of food applications were predicted by
      potential harm, potential benefits, science knowledge, and familiarity; experts'
      estimates were predicted only by harm and benefits. Lay estimates of the risk of
      medical applications were predicted by potential harm; experts' estimates were
      predicted by potential benefits, number and type of people exposed, and science
      knowledge. We discuss the implications of the results for risk communication
      about and management of different types of biotechnologies.

PMID- 15563296
TI  - Travel risks in a time of terror: judgments and choices.
AB  - Shortly after the 2002 terrorist attacks in Bali, readers of Conde Nast Traveler
      magazine were surveyed regarding their views on the risks of travel to various
      destinations. Their risk estimates were highest for Israel, and lowest for
      Canada. Estimates for the different destinations correlated positively with (1)
      one another, (2) concern over aspects of travel that can make one feel at risk
      (e.g., sticking out as an American), (3) worries about other travel problems
      (e.g., contracting an infectious disease), and (4) attitudes toward risk.
      Respondents' willingness to travel to a destination was predicted well by whether
      their estimate of its risk was above or below their general threshold for the
      acceptability of travel risks. Overall, the responses suggest orderly choices,
      based on highly uncertain judgments of risks. Worry played a significant role in
      these choices, even after controlling for cognitive considerations, thereby
      supporting the recently proposed "risk as feelings" hypothesis. Thus, even among
      people who have generally consistent and defensible beliefs, emotions may affect
      choices. These results emerged with people selected for their interest in and
      experience with the decision domain (travel), but challenged to incorporate a new
      concern (terror).

PMID- 15563297
TI  - Reactions to genetically modified food crops and how perception of risks and
      benefits influences consumers' information gathering.
AB  - Previous research has reported strong consumer perception that genetically
      modified (GM) food crops may lead to adverse outcomes in a number of different
      areas. This is despite the widespread promulgation of the potential benefits and
      opportunities ascribed to the same technology by many scientists and other
      experts. A computer-based information gathering and evaluation task was completed
      by 198 adults to assess the extent to which their initial focus on the dangers or
      opportunities of genetic modification, or both, could be ascribed to the manner
      in which they gathered information on the topic (heuristically vs.
      systematically). Results did not confirm the hypothesis that initial focus
      (risks, benefits, or both) predicted ongoing information gathering and evaluation
      behavior. Moreover, also contrary to prediction, most participants primarily used
      systematic strategies when deriving their initial position, regardless of that
      opinion. Participants found it difficult to achieve a balanced perspective on GM
      food crop, even though balanced argument, as measured by order of story selection
      and time spent reading, was preferred as the source of information. Perceived
      importance is probably the most influential variable determining information
      gathering about issues or events to which a level of risk is attached.

PMID- 15563298
TI  - Accommodating uncertainty in comparative risk.
AB  - Comparative risk projects can provide broad policy guidance but they rarely have
      adequate scientific foundations to support precise risk rankings. Many extant
      projects report rankings anyway, with limited attention to uncertainty.
      Stochastic uncertainty, structural uncertainty, and ignorance are types of
      incertitude that afflict risk comparisons. The recently completed New Jersey
      Comparative Risk Project was innovative in trying to acknowledge and accommodate
      some historically ignored uncertainties in a substantive manner. This article
      examines the methods used and lessons learned from the New Jersey project. Monte
      Carlo techniques were used to characterize stochastic uncertainty, and
      sensitivity analysis helped to manage structural uncertainty. A deliberative
      process and a sorting technique helped manage ignorance. Key findings are that
      stochastic rankings can be calculated but they reveal such an alarming degree of
      imprecision that the rankings are no longer useful, whereas sorting techniques
      are helpful in spite of uncertainty. A deliberative process is helpful to counter
      analytical overreaching.

PMID- 15563299
TI  - Intended message versus message received in hypothetical physician risk
      communications: exploring the gap.
AB  - We examined the risk perception that is derived from hypothetical physician risk
      communications. Subjects (n= 217) completed a questionnaire on the Web for $3.
      Subjects were presented with four hypothetical cancer risk scenarios that
      included a physician risk communication in one of three risk communication
      formats: verbal only, verbal plus numeric probability as a percent, and verbal
      plus numeric probability as a fraction. In each scenario, subjects were asked to
      imagine themselves as the patient described and to state their perceived personal
      susceptibility to the cancer (i.e., risk perception) on a 0 to 100 scale, as well
      as responses to other measures. Subjects' risk perceptions were highly variable,
      spanning nearly the entire probability scale for each scenario, and the degree of
      variation was only slightly less in the risk communication formats in which a
      numeric statement of risk was provided. Subjects were more likely to overestimate
      than underestimate their risk relative to the stated risk in the numeric
      versions, and overestimation was associated with the belief that the physician
      minimized the risk so they wouldn't worry, innumeracy, and worry, as well as
      decisions about testing for the cancer. These results demonstrate significant
      gaps between the intended message and the message received in physician risk
      communications. Implications for medical decisions, patient distress, and future
      research are discussed.

PMID- 15563300
TI  - An emotion-based model of risk perception and stigma susceptibility: cognitive
      appraisals of emotion, affective reactivity, worldviews, and risk perceptions in
      the generation of technological stigma.
AB  - A study (N=198) was conducted to examine hypotheses derived from an emotion-based
      model of stigma responses to radiation sources. A model of stigma susceptibility
      is proposed in which affective reactions and cognitive worldviews activate
      predispositions to appraise and experience events in systematic ways that result
      in the generation of negative emotion, risk perceptions, and stigma responses.
      Results of structural equation modeling supported the hypotheses. Radiation
      sources that scored higher on a measure of stigma were included in the analyses
      (i.e., nuclear power plants, radioactive waste from nuclear power plants,
      radiation from nuclear weapons testing). Individual differences in negative
      reactivity and worldviews were associated with the strength of emotional
      appraisals that were associated, in turn, with negative emotion toward
      stigmatized radiation sources. As hypothesized, the model fit better with
      perceived risk as a function of negative emotion rather than vice versa. Finally,
      a measure of stigma was associated with negative emotion and, to a lesser extent,
      with risk perceptions. Risk communication about stigmatized objects may benefit
      from a more complete understanding of how affective and emotional reactions are
      constructed and the routes through which they affect responses and behaviors.

PMID- 15563301
TI  - Effects of context and feelings on perceptions of genetically modified food.
AB  - Recently, there has been a surge of interest in the role of feelings in framing
      perceptions and decisions about risk, yet no study has specifically examined the
      impact of feelings on perceptions/judgments about biotechnology. This exploratory
      study investigated current perceptions of genetically modified (GM) food to
      examine (1) the effects of context (making judgments about GM food at the same
      time as rating other current areas of concern), and (2) the effect of feelings of
      dread (integral affect) and background feelings of stress (negative incidental
      affect) on risk judgments about GM food. An established psychometric method
      (semantic differential task) used with a sample of 126 adults (recruited "topic
      blind," mostly from a student population) showed that, when rated in the context
      of other current concerns such as human cloning and Creutzfeldt-Jakob disease
      (CJD), there was less concern about GM food than might have been anticipated.
      Participants were recruited "topic-blind" in order to ensure that they were
      unaware that the focus of the research was on GM food specifically (and thus
      preventing biased recruitment to the study). Relative to 19 other current
      concerns GM food was "not dreaded," not viewed as "unethical," was judged as
      "controllable," and was seen as the least "risky" of all the issues studied. GM
      food was viewed as a "hot topic," a new risk, and as relatively unnatural
      (although it was not the highest rated concern on this scale). Ratings of risks
      across concerns by individuals experiencing high levels of negative incidental
      affect (stress) did not differ significantly from those reporting low stress.

PMID- 15563302
TI  - Psychological determinants of willingness to taste and purchase genetically
      modified food.
AB  - Decreasing acceptance of biotechnologies over time has been reported in Europe.
      Studies claim that attitudes are negative, even hostile, and that people are very
      worried about genetic engineering in food and medicine. However, such studies are
      mostly based on surveys and these have significant methodological problems, such
      as low response rates, which may indicate that only those with strong views
      respond, thus biasing the sample. Here an alternative method, involving "topic
      blind" recruitment of participants and a behavioral measure (food tasting), was
      used. We show that in a topic-blind sample of 100 individuals, 93% willingly
      tasted and ate what they believed to be genetically modified (GM) food in an
      experimental setting, and 48% said they would buy GM food in the future, results
      that are surprising in the context of other reports about attitudes and
      intentions toward GM food. Purchasers and nonpurchasers differed in their
      attitudes toward GM food on key risk-related scales (particularly on a dread-not
      dread scale--a measure of integral affect--and an ethical-unethical scale).
      Despite these differences, however, and despite their negative attitude, most
      nonpurchasers (85.7%) still tasted the GM apple. Incidental affect (state stress
      and trait worry) was not found to influence risk-related judgments about GM food.
      Integral affect (dread of GM plants and animals used for food) and concerns about
      the future risks of GM animals in food were found to be key predictors of
      willingness to purchase GM food.

PMID- 15563303
TI  - Risk and climate change: perceptions of key policy actors in Canada.
AB  - This article examines factors that predict perceptions of risk associated with
      global climate change. The research focuses on the perceptions of those
      associated with climate change policy making in the prairie region of Canada. The
      data are from an online survey (n=851) of those policy actors. The analysis
      integrates several dominant approaches to the study of risk perception:
      psychometric approaches that examine the effects of cognitive structure;
      demographic assessments that examine, for example, differences in perception
      based on gender or family status; and political approaches that suggest that
      one's position in the policy process may affect his or her perceived risk.
      Attitudes toward climate change are to a degree predicted by all of these
      factors, but only when indirect effects are observed. Sociodemographic
      characteristics have little direct effect on perceived risk, but do affect
      general beliefs that affect risk perceptions. Perceived risk is related more
      strongly to these general beliefs or world views than to more specific beliefs
      about the effects of climate change on weather patterns. Position within the
      policy process also contributes to our understanding of perceptions, with
      industry and governmental actors demonstrating similar attitudes, which contrast
      with environmental groups and university researchers.

PMID- 15563305
TI  - Angiogenesis: now and then.
AB  - Angiogenesis or new blood vessel formation plays an essential role during
      embryogenesis, adult vascular remodeling and in several pathological disorders,
      as in tumor development. Although sprouting of blood vessels is the principal
      angiogenic mechanism, additional ones, such as the recruitment of bone marrow
      derived cells, have recently been described. These processes are controlled by
      several molecules, although members of the VEGF family of angiogenic factors and
      its receptors seem to be the main mediators. Initially, VEGF receptors were
      described as endothelial specific; however, further studies have reported their
      presence in several types of cells of non-endothelial origin, such as tumor
      cells. This VEGF receptor altered expression has suggested an angiogenesis
      independent growth advantage mechanism on certain types of cancers by the
      generation of autocrine loops. A possible role in tumorigenesis and a potential
      novel target in cancer therapy have been hypothesized. Detection of other
      receptors and molecules considered to be angiogenic players has also been
      observed on tumor cells. Currently, their clinical significance as well as their
      potential as therapeutic targets for the treatment of certain cancers is being
      evaluated, having in mind the future development of promising mechanism-based
      therapies. The aspects mentioned above are the main focus of this review, which
      aims to throw light on recent findings respecting angiogenesis and novel
      therapeutic approaches.

PMID- 15563306
TI  - Histological quantitation of tumour angiogenesis.
AB  - Tumours establish their blood supply via a number of processes in addition to
      angiogenesis. These include vasculogenesis, vascular remodelling, intussusception
      and possibly vascular mimicry in certain tumours. The mainstay of the assessment
      of tumour vascularity has been counting the number of immunohistochemically
      identified microvessels in vascular hot spots. Nevertheless, several other
      techniques are available, including Chalkley counting, vascular grade and the use
      of image analysis systems. Angiogenic activity can furthermore be assessed in
      histological samples by measuring the molecules involved in the establishment of
      the tumour vasculature, including angiogenic growth factors and their receptors,
      cell adhesion molecules, proteases and markers of activated, proliferating,
      cytokine stimulated or angiogenic vessels, such as CD105. Measuring the maturity
      of vessels may give an indication of the proportion of the tumour vasculature
      that is functional. Other reagents that can identify hypoxia-activated pathways
      are also being developed. The histological assessment of tumour vascularity is
      mainly used in the research setting but may also have applications in the clinic
      if appropriate methodology and trained observers perform the studies. Gene arrays
      may be able to provide an angiogenesis profile. Continued study into the
      processes involved in generating a tumour blood supply is likely to identify new
      markers that may be more accurate measures.

PMID- 15563307
TI  - Tumour angiogenesis: vascular growth and survival.
AB  - Angiogenesis starts at the edge of a malignant epithelial tumour concurrently
      with tumour cell invasion and stromatogenesis, i.e. the formation of specific
      connective tissue stroma amenable to easy penetration by endothelial and tumour
      cells. However, as the tumour continues its growth, the edge becomes the inner
      tumour area, and a new invading tumour front is formed by the multiplying
      malignant cells which outflank the initial edge. This process, which repeats
      itself again and again, forms the "relay race" model of tumour vascular growth
      and regression. At the heart of the tumour unfavourable environmental conditions
      prevail -- hypoxia, acidity, lack of nutrients, failure of waste removal, and
      apoptosis rather than proliferation. Blood vessels and tumour cells are greatly
      decreased, but do not vanish, as tumour cells are shifting to anaerobic
      glycolysis, and blood vessels are turning into anti-apoptotic pathways --
      vascular survival ability (VSA). Thus, assessing vascular density (VD) by simply
      counting "hot spots" at the edge of a tumour, where conditions are most
      favourable, is futile; it may reflect tumour angiogenic activity (TAA), but is
      not representative of genuine tumour vasculature. By combining vessel counts at
      the invading tumour front with those of the inner tumour areas a complete picture
      of tumour VD can be achieved. The thus formed four patterns of vascularization,
      designated as "edvin" (edge vsinner tumour area), are: edvin 1: low TAA/low VSA;
      edvin 4: high TAA/high VSA; edvin 2: low TAA/high VSA; and edvin 3: high TAA/low
      VSA. It is expected that this scheme will prove useful in the field of
      chemoradiotherapy and anti-angiogenic treatment.

PMID- 15563308
TI  - Imaging tumor angiogenesis with fluorescent proteins.
AB  - We have developed three unique mouse models to image angiogenesis with
      fluorescent proteins, which are described in this review. First, we have adapted
      the surgical orthotopic implantation (SOI) model to image angiogenesis of human
      tumors labeled with green fluorescent protein (GFP) transplanted in nude mice.
      The nonluminous induced capillaries are clearly visible by contrast against the
      very bright tumor fluorescence examined either intravitally or by whole-body
      imaging in real time. Intravital images of an SOI model of human pancreatic
      tumors expressing GFP visualized angiogenic capillaries at both primary and
      metastatic sites. Whole-body optical imaging showed that blood vessel density
      increased linearly over a 20-week period in an SOI model of human breast cancer
      expressing GFP. Opening a reversible skin-flap in the light path markedly reduces
      signal attenuation, increasing detection sensitivity many-fold and enabling
      vessels to be externally visualized in GFP-expressing tumors growing on internal
      organs. The second model utilizes dual-color fluorescence imaging, effected by
      using red fluorescent protein (RFP)-expressing tumors growing in GFP-expressing
      transgenic mice that express GFP in all cells. This dual-color model visualizes
      with great clarity the details of the tumor-stroma interaction, especially tumor
      induced angiogenesis. The GFP-expressing tumor vasculature, both nascent and
      mature, are readily distinguished interacting with the RFP-expressing tumor
      cells. Using a spectral imaging system based on liquid crystal tunable filters,
      we were able to separate individual spectral species on a pixel-by-pixel basis.
      Such techniques non-invasively visualized the presence of host GFP-expressing
      vessels within an RFP-labeled orthotopic human breast tumor by real-time whole
      body imaging. The third model involves a transgenic mouse in which the regulatory
      elements of the stem cell marker nestin drive GFP. The nestin-GFP mouse expresses
      GFP in areas of the brain, hair follicle stem cells, and in a network of blood
      vessels in the skin interconnecting hair follicles. RFP-expressing tumors
      transplanted to nestin-GFP mice enable specific visualization of nascent vessels
      in skin-growing tumors such as melanoma. Thus, fluorescent proteins expressed in
      vivo offer very high resolution and sensitivity for real-time imaging of
      angiogenesis.

PMID- 15563309
TI  - The contribution of vascular basement membranes and extracellular matrix to the
      mechanics of tumor angiogenesis.
AB  - The goal of this review is to highlight the contribution of extracellular matrix
      and vascular basement membranes to the regulation of angiogenesis and tumor
      progression. Here we present a new concept that vascular basement membrane
      influences endothelial cells and possibly other cell types in a solid state
      assembled form, and also in a degraded solution state form. Depending on the
      structural integrity, composition and exposure of cryptic sites, the vascular
      basement membrane proteome exerts functional influences on proliferating and
      resting endothelial cells. This review provides the reader with an appreciation
      of this newly evolved concept in the area of vascular biology.

PMID- 15563310
TI  - Molecular regulation of the VEGF family -- inducers of angiogenesis and
      lymphangiogenesis.
AB  - The vascular endothelial growth factor (VEGF) family of secreted glycoproteins
      are critical inducers of angiogenesis (growth of blood vessels) and
      lymphangiogenesis (growth of lymphatic vessels). These proteins are attractive
      therapeutic targets for blocking growth of blood vessels and lymphatics in tumors
      and thereby inhibiting the growth and spread of cancer -- in fact, the first VEGF
      inhibitor has recently entered the clinic for treatment of cancer. In addition,
      the VEGFs are being considered for stimulation of angiogenesis in the context of
      ischemic disease and lymphangiogenesis for treatment of lymphedema. These
      therapeutic possibilities have focused great interest on the molecular regulation
      of VEGF family members. Much has been learned in the past five years about the
      mechanisms controlling the action of the VEGFs, including the importance of
      hypoxia, proteolysis, transcription factors and RNA splicing. An understanding of
      these mechanisms offers broader opportunities to manipulate expression and
      activity of the VEGFs for treatment of disease.

PMID- 15563311
TI  - The chemokine system -- a major regulator of angiogenesis in health and disease.
AB  - The chemokine system controls leukocyte trafficking during homeostasis as well as
      during inflammation and is necessary for the linkage between innate and adaptive
      immunity. Tissue regulation outside the hematopoietic compartment, for instance,
      angiogenesis, organogenesis and tumor development, growth and metastasis, is
      another important function of the chemokine system. The chemokine-mediated
      regulation of angiogenesis is highly sophisticated and fine tuned, and involves
      pro-angiogenic chemokines, for instance, CXCL8/IL8 interacting with the CXCR2
      receptor, and anti-angiogenic (i.e. angiostatic) chemokines, for instance,
      CXCL10/IP10 interacting with the CXCR3 receptor. Chemokines also regulate
      angiogenesis in a receptor-independent manner by means of a perturbation of bFGF
      and VEGF function. The current review focuses on the influence of the chemokine
      system in angiogenesis. Examples of the delicate angiogenesis regulation by the
      chemokine system in, for instance, wound healing and of the dysregulation in, for
      instance, tumor development are provided along with the interesting phenomenon of
      molecular piracy of host-encoded genes within the chemokine system. This
      phenomenon is a general strategy to circumvent and exploit the immune system --
      and thereby improve survival -- for many viruses. Yet, a certain group of
      herpesviruses -- the gamma2-herpesviruses -- encode a functional CXCR2 receptor
      homolog that is activated by angiogenic chemokines and antagonized by angiostatic
      chemokines, and this particular gene seems to cause the development of a vascular
      tumor -- Kaposi's sarcoma -- in the host.

PMID- 15563312
TI  - Endogenous angiogenesis inhibitors.
AB  - When the FDA commissioner announced in February 2004 the approval of Avastin for
      the treatment of patients with colon cancer, he called angiogenesis inhibitors a
      fourth modality of anti-cancer therapy. Because angiogenesis inhibitors are
      relatively less toxic than conventional chemotherapy and have a lower risk of
      drug resistance, they may also represent a new class of anti-cancer agents, some
      of which have sufficiently reduced toxicity that they may be safely used long
      term. These include immunotherapy, vaccines, telomerase inhibitors, apoptosis
      inducers, low dose metronomic chemotherapy, novel hormonal therapies, gene
      therapy and others. However, at least 16 endogenous angiogenesis inhibitors have
      been discovered in the circulation, and/or in the extracellular matrix. These may
      become the safest and least toxic of anti-cancer therapies. Four are already
      being administered by injection in clinical trials for cancer. Recently, it has
      been reported that at least two endogenous angiogenesis inhibitors can be
      significantly increased in humans (endostatin), and in mice (thrombospondin), by
      oral administration of small molecules which themselves are already FDA approved
      for other uses. This finding suggests several new clinical applications for the
      future, including the possibility of guiding the use of angiogenesis inhibitors
      by blood or urinary biomarkers, currently being developed, that may detect the
      presence of cancer before it is symptomatic, or before it can be located by
      conventional methods.

PMID- 15563313
TI  - Vasculogenic mimicry.
AB  - The term vasculogenic mimicry describes the formation of fluid-conducting
      channels by highly invasive and genetically dysregulated tumor cells. Two
      distinctive types of vasculogenic mimicry have been described. Vasculogenic
      mimicry of the tubular type may be confused morphologically with endothelial cell
      lined blood vessels. Vasculogenic mimicry of the patterned matrix type in no way
      resembles blood vessels morphologically or topologically. Matrix proteins such as
      laminin, heparan sulfate proteoglycan, and collagens IV and VI have been
      identified in these patterns. The patterned matrix anastomoses with blood
      vessels, and systemically injected tracers co-localize to these patterns.
      Vasculogenic mimicry of the patterned matrix type has been identified in uveal,
      cutaneous and mucous membrane melanomas, inflammatory and ductal breast
      carcinoma, ovarian and prostatic carcinoma, and soft tissue sarcomas, including
      synovial sarcoma rhabdomyosarcoma, osteosarcoma, and pheochromocytoma. Because
      the microcirculation of many tumors may be heterogeneous -- including
      incorporated or co-opted vessels, angiogenic vessels, mosaic vessels, and
      vasculogenic mimicry of the tubular and patterned matrix types -- therapeutic
      regimens that target angiogenesis alone may be ineffective against highly
      invasive tumors that contain patterned matrices. Vasculogenic mimicry provides an
      opportunity to investigate the interrelationships between the genetically
      dysregulated invasive tumor cell, the microenvironment, and the malignant switch.

PMID- 15563314
TI  - Biology of the lymphatic marker LYVE-1 and applications in research into
      lymphatic trafficking and lymphangiogenesis.
AB  - The pace of research into the lymphatic system continues to accelerate with the
      availability of new molecular markers. One such marker, LYVE-1, the lymphatic
      receptor for the extracellular matrix mucopolysaccharide hyaluronan, has been a
      key component of many important studies on embryonic and tumour-induced
      lymphangiogenesis, and continues to be used for the detection and isolation of
      lymphatic endothelial cells. However, LYVE-1 is interesting in its own right.
      Being a member of the Link protein family whose only other major hyaluronan
      receptor is directly involved in leukocyte migration and tumour metastasis, LYVE
      1 is already implicated in the trafficking of cells within lymphatic vessels and
      lymph nodes. The current challenge is to determine the precise roles played by
      LYVE-1 and other scavenger type receptors in the immune functions of the
      lymphatics as well as to use LYVE-1 and other markers to investigate the way in
      which tumours exploit lymphatic vessels for metastasis.

PMID- 15563315
TI  - Lymphangiogenic growth factors as markers of tumor metastasis.
AB  - Understanding the complex process of tumor metastasis is a problem which has
      challenged both clinician and scientist for well over 100 years. Defining
      molecular markers which reflect the metastatic potential of a tumor has also
      proved elusive. Recently, members of the vascular endothelial growth factor
      (VEGF) family of glycoproteins have been demonstrated to be potent mediators of
      both blood vessel and lymphatic vessel formation in the context of tumor biology.
      Experimental studies in animal models combined with extensive clinicopathological
      data provide a compelling case indicating that members of the VEGF family play a
      key role in the formation of metastases in a broad range of solid tumors. The
      question of whether VEGF signaling pathways can now serve as therapeutic targets
      alone, or in combination with other forms of anti-cancer agents, needs to be
      addressed.

PMID- 15563316
TI  - Balancing risks and benefits in pain medicine: wither Vioxx.

PMID- 15563318
TI  - Post-deployment pain: a need for rapid detection and intervention.

PMID- 15563319
TI  - The longitudinal occurrence and impact of comorbid chronic pain and chronic
      depression over two years in continuing care retirement community residents.
AB  - OBJECTIVE: To describe the longitudinal course of depressive symptoms and pain
      experienced by continuing care retirement community (CCRC) residents and to
      investigate the impact of comorbid chronic activity-limiting pain and chronic
      high depressive symptoms on physical functioning and health service use. METHODS:
      This longitudinal study of 169 CCRC residents involved five assessments (baseline
      and four in-person interviews at 6-month intervals). The Geriatric Depression
      Scale (GDS), questions drawn from the McGill Pain Questionnaire, and self-report
      data on physical functioning and health care use were assessed. Individuals
      reporting activity-limiting pain and those with GDS scores > or =11 at three or
      more assessments were considered to have chronic pain or chronic depression,
      respectively. The analysis sample included 169 CCRC residents. Multivariate
      logistic regression was used to test hypotheses. RESULTS: Pain and depressive
      symptoms were characterized by longitudinal stability. Of the sample, 37% met the
      criteria for chronic activity-limiting pain, 21% met the criteria for chronic
      high depressive symptoms, and 13% were comorbid. Adjusting for age and health
      conditions, those with chronic activity-limiting pain were five times more likely
      than those in the lowest pain group to persistently be in the worst two quartiles
      of physical functioning, as were those with even one GDS score >5. The odds of
      poor physical functioning were 11.2 times greater in those with comorbid chronic
      pain and depression. Comparable greater odds were seen in this sample for
      frequency of medical care visits (adjusted odds ratio AOR]=12.4) and consistently
      high use of all medical services (AOR=3.5). CONCLUSIONS: Pain and depressive
      symptoms were both common and appeared remarkably stable over time. Depressive
      symptoms contributed significantly to the prediction of impairment associated
      with pain, and identification and treatment of such symptoms, even minor
      symptoms, could reduce pain-related impairment and health care costs in the
      elderly.

PMID- 15563320
TI  - On the reliability and validity of physician ratings for vulvodynia and the
      discriminant validity of its subtypes.
AB  - OBJECTIVE: This study aimed to test the reliability and validity of physician
      ratings in a broadly defined sample of women with vulvodynia and to examine the
      external validity of the vulvodynia subtypes. DESIGN: Participants were 50 women
      who were independently diagnosed with vulvodynia by two study gynecologists.
      Physician ratings corresponding to Friedrich's three criteria for vulvar
      vestibulitis were taken at the two examinations. Each participant's diagnosis was
      subtyped as vulvar vestibulitis (VV) or dysesthetic vulvodynia (DV) based upon
      the physician ratings. Participants completed standardized measures of pain,
      sexual function, psychological function, and quality of life to examine the
      discriminant validity of the subtypes. RESULTS: Test-retest reliability for the
      physician ratings of Friedrich's three criteria was stable for two of the three
      criteria (i.e., pain on attempted vaginal entry and tenderness to pressure
      localized within the vulvar vestibule). When these criteria were used to
      categorize participants as having VV or DV, the subtypes were not statistically
      different for measures used to examine the discriminant validity of the subtypes.
      While the distribution of patients changed when premenopausal state was added to
      the inclusion criteria for VV, the subtypes differed little on the outcome
      measures. CONCLUSIONS: Findings from the present study suggest that physician
      ratings for Friedrich's criteria can be operationalized and found to be reliable
      and valid in a wide range of women with vulvodynia. The absence of differences
      between subtypes on measures of pain, sexual function, psychological function,
      and quality of life challenge the clinical significance of these subtypes and
      support the theory that vulvodynia represents a continuum of chronic vulvar pain
      rather than two distinct entities.

PMID- 15563321
TI  - Do the second-generation "atypical neuroleptics" have analgesic properties? A
      structured evidence-based review.
AB  - STUDY DESIGN: This is a structured, evidence-based review of all available
      studies on the potential effectiveness of the atypical neuroleptics for the
      treatment of pain (analgesia). To determine what evidence, if any, exists for, or
      against, the effectiveness of the atypical neuroleptics for analgesia. SUMMARY OF
      BACKGROUND DATA: There has been significant controversy over whether the
      conventional neuroleptics (non-atypicals) have analgesic properties. A recent
      review (Patt et al. 1994) did conclude that the evidence for effectiveness was
      sparse, except for methotrimeprazine. However, that review did not include a new
      class of neuroleptics: the atypicals such as olazapine, risperidone, quetiapine,
      etc. METHODS: A computer and manual search for studies relating to the atypicals
      and their analgesic effectiveness produced 10 studies/reports. These were
      reviewed in detail, and information relating to the above problem was abstracted
      and placed into tabular form. Each report was also categorized by the type of
      study it represented according to the guidelines developed by the Agency for
      Health Care Policy and Research (AHCPR). The strength and consistency of the
      evidence represented by the 10 studies were then categorized according to the
      AHCPR guidelines. Conclusions of this review were based on these results. RESULTS
      OF DATA SYNTHESIS: Of the 10 studies/reports, four were characterized by AHCPR
      guidelines as Type II (experimental), two were Type III (quasiexperimental), two
      were Type IV (nonexperimental), and two were Type V (case reports). Of these
      studies/reports, 90% indicated that the atypicals did have an analgesic effect.
      The overall strength and consistency of this evidence using the AHCPR guidelines
      was, therefore, categorized as B (generally consistent from Type II, Type III,
      and Type IV studies). CONCLUSIONS: Based on the above results, it was concluded
      that the reviewed data were generally consistent, suggesting that some of the
      atypicals may have an analgesic effect. There were, however, few double-blind,
      placebo-controlled studies, and many of the reports/studies had less than 50
      patients. As such, this question requires further research.

PMID- 15563322
TI  - Modulation of central hypersensitivity by nociceptive input in chronic pain after
      whiplash injury.
AB  - OBJECTIVE: Chronic pain after whiplash injury is associated with hypersensitivity
      of the central nervous system to peripheral stimulation. It is unclear whether
      central hypersensitivity is modulated by peripheral nociceptive input. We
      hypothesized that changes in nociceptive input would correlate with changes in
      magnitude of central hypersensitivity. DESIGN: Fifteen patients with chronic pain
      after whiplash injury were investigated. Changes in nociceptive input were
      induced by infiltration of painful and tender muscles with bupivacaine (0.25%).
      Such infiltrations produce either pain reduction or pain enhancement, the latter
      effect probably resulting from transient injection-induced trauma. We used this
      individual variability in correlation analyses. Changes in intensity of neck
      pain, as assessed by a visual analog scale (VAS), after infiltration were assumed
      to reflect changes in nociceptive input. Changes in pressure pain thresholds
      recorded at healthy tissues (nonpainful point of the neck and the second toe)
      were used to measure changes in central hypersensitivity. The correlations
      between the change in VAS score and changes in pressure pain thresholds 15
      minutes after infiltration were analyzed. RESULTS: Statistically significant
      negative correlations were found between change in VAS score and changes in
      threshold measurements performed at the neck, but not at the toe. CONCLUSIONS:
      Different mechanisms underlie hyperalgesia localized at areas surrounding the
      site of pain and hyperalgesia generalized to distant body areas. Central
      hypersensitivity as a determinant of neck pain is probably a dynamic condition
      that is influenced by the presence and activity of a nociceptive focus.

PMID- 15563323
TI  - Dynamic object individuation in rhesus macaques: a study of the tunnel effect.
AB  - A manual-search experiment with rhesus monkeys (Macaca mulatta) explored dynamic
      object individuation in the tunnel effect: Subjects watched as a lemon rolled
      down a ramp and came to rest behind a tunnel (Occluder 1) and then as a kiwifruit
      emerged and became occluded at the end of its path behind a screen (Occluder 2).
      When the kiwifruit emerged at about the time that the lemon should have (had it
      continued its motion), subjects searched for food only behind Occluder 2
      apparently perceiving the lemon to have transformed into a kiwifruit on the basis
      of spatiotemporally continuous motion. In contrast, when a brief pause
      interrupted the occlusion of the lemon and the emergence of the kiwifruit,
      monkeys searched for food behind both occluders. With further control conditions,
      this experiment demonstrates a spatiotemporal bias-similar to a bias found in
      adult visual perception-in the computation of object persistence in the context
      of a dynamic correspondence problem.

PMID- 15563324
TI  - From vulnerability to resilience: learning orientations buffer contingent self
      esteem from failure.
AB  - An experiment examined the buffering effects of a learning orientation following
      failure in a domain of contingent self-worth. Participants' academic
      contingencies of self-worth (CSW) and priming with theories of intelligence
      interacted to affect vulnerability of self-esteem to failure. Participants who
      had high academic CSW and were primed with an entity theory of intelligence
      experienced lower self-esteem and higher negative affect following failure than
      following success on an academic test, but these effects were eliminated when
      participants with high academic CSW were primed with an incremental theory of
      intelligence. This study shows that endorsing a learning orientation is an
      effective way to minimize threat to self-esteem among students whose self-worth
      is highly contingent on academics and may allow them to persist in the face of
      challenges and to learn from failure.

PMID- 15563325
TI  - Separable neural components in the processing of black and white faces.
AB  - In a study of the neural components of automatic and controlled social
      evaluation, White participants viewed Black and White faces during event-related
      functional magnetic resonance imaging. When the faces were presented for 30 ms,
      activation in the amygdala-a brain region associated with emotion-was greater for
      Black than for White faces. When the faces were presented for 525 ms, this
      difference was significantly reduced, and regions of frontal cortex associated
      with control and regulation showed greater activation for Black than White faces.
      Furthermore, greater race bias on an indirect behavioral measure was correlated
      with greater difference in amygdala activation between Black and White faces, and
      frontal activity predicted a reduction in Black-White differences in amygdala
      activity from the 30-ms to the 525-ms condition. These results provide evidence
      for neural distinctions between automatic and more controlled processing of
      social groups, and suggest that controlled processes may modulate automatic
      evaluation.

PMID- 15563326
TI  - The eyes are right when the mouth is wrong.
AB  - When describing visual scenes, speakers typically gaze at objects while preparing
      their names. In a study of the relation between eye movements and speech, a
      corpus of self-corrected speech errors was analyzed. If errors result from rushed
      word preparation, insufficient visual information, or failure to check prepared
      names against objects, speakers should spend less time gazing at referents before
      uttering errors than before uttering correct names. Counter to predictions, gazes
      to referents before errors (e.g., gazes to an axe before saying "ham-" [hammer])
      highly resembled gazes to referents before correct names (e.g., gazes to an axe
      before saying "axe"). However, speakers gazed at referents for more time after
      initiating erroneous compared with correct names, apparently while they prepared
      corrections. Assuming that gaze nonetheless reflects word preparation, errors
      were not associated with insufficient preparation. Nor were errors systematically
      associated with decreased inspection of objects. Like gesture, gaze may
      accurately reflect a speaker's intentions even when the accompanying speech does
      not.

PMID- 15563327
TI  - Learned fear of "unseen" faces after Pavlovian, observational, and instructed
      fear.
AB  - This study compared fear learning acquired through direct experience (Pavlovian
      conditioning) and fear learning acquired without direct experience via either
      observation or verbal instruction. We examined whether these three types of
      learning yielded differential responses to conditioned stimuli (CS+) that were
      presented unmasked (available to explicit awareness) or masked (not available to
      explicit awareness). In the Pavlovian group, the CS+ was paired with a mild
      shock, whereas the observational-learning group learned through observing the
      emotional expression of a confederate receiving shocks paired with the CS+. The
      instructed-learning group was told that the CS+ predicted a shock. The three
      groups demonstrated similar levels of learning as measured by the skin
      conductance response to unmasked stimuli. As in previous studies, participants
      also displayed a significant learning response to masked stimuli following
      Pavlovian conditioning. However, whereas the observational-learning group also
      showed this effect, the instructed-learning group did not.

PMID- 15563328
TI  - The ups and downs of attributional ambiguity: stereotype vulnerability and the
      academic self-knowledge of African American college students.
AB  - This research examined whether stereotype vulnerability-the tendency to expect,
      perceive, and be influenced by negative stereotypes about one's social category
      is associated with uncertainty about one's academic self-knowledge in two
      important ways. We predicted that stereotype-vulnerable African American students
      would (a) know less about how much they know than less vulnerable students do and
      (b) have unstable academic efficacy. In Study 1, Black and White participants
      took a verbal test and indicated the probability that each of their answers was
      correct. As expected, stereotype-vulnerable Black participants were more
      miscalibrated than other participants. In Study 2, participants completed
      measures of self-efficacy twice daily for 8 days. Also as expected, the academic
      efficacy of stereotype-vulnerable Blacks fluctuated more-and more extremely-than
      that of other participants. The results suggest that, in addition to undermining
      intellectual performance, stigma interferes with academic self-knowledge.

PMID- 15563329
TI  - Self-fulfilling prophecies: the synergistic accumulative effect of parents'
      beliefs on children's drinking behavior.
AB  - This research examined whether mothers' and fathers' beliefs about their
      children's alcohol use had cumulative self-fulfilling effects on their children's
      future drinking behavior. Analyses of longitudinal data acquired from 115 seventh
      grade children and their mothers and fathers were consistent with synergistic
      accumulation effects for negative beliefs: Parents' beliefs predicted the
      greatest degree of confirmatory behavior from children when both mothers and
      fathers overestimated their children's alcohol use. Results did not support
      synergistic accumulation effects for positive beliefs: Children's predicted
      future alcohol use was similar regardless of whether one parent or both
      underestimated their child's alcohol use. These findings suggest that the
      generally small self-fulfilling effects reported in the literature may
      underestimate the power of negative self-fulfilling prophecies to harm targets
      because studies have not taken into consideration the possibility that negative
      self-fulfilling prophecies may be more likely than positive ones to accumulate
      across multiple perceivers.

PMID- 15563330
TI  - Fatal attraction: the effects of mortality salience on evaluations of
      charismatic, task-oriented, and relationship-oriented leaders.
AB  - A study was conducted to assess the effects of mortality salience on evaluations
      of political candidates as a function of leadership style. On the basis of terror
      management theory and previous research, we hypothesized that people would show
      increased preference for a charismatic political candidate and decreased
      preference for a relationship-oriented political candidate in response to subtle
      reminders of death. Following a mortality-salience or control induction, 190
      participants read campaign statements by charismatic, task-oriented, and
      relationship-oriented gubernatorial candidates; evaluated their preferences for
      each candidate; and voted for one of them. Results were in accord with
      predictions. The theoretical and practical implications of these findings are
      considered.

PMID- 15563331
TI  - Automatic semantic activation is no myth: semantic context effects on the N400 in
      the letter-search task in the absence of response time effects.
AB  - The claim that semantic activation is an automatic process was recently called a
      myth, on the basis of the finding that if letter search is performed on a prime
      word, semantic priming effects on response time are eliminated, whereas
      repetition effects are preserved. The absence of semantic activation, however,
      cannot be validly inferred from the lack of response time effects, and converging
      evidence is needed. To this end, we examined the event-related potential
      correlate of priming, the N400 amplitude modulation, in a letter-search priming
      paradigm. Our experiment replicated the response time effects and demonstrated
      that the N400 amplitude successfully differentiates cross-case repetition
      priming, semantic priming, and neutral conditions. The results clearly indicate
      that the meaning of the prime word was processed and that semantic activation
      indeed was present in the letter-search task. The notion that semantic activation
      is an automatic process should not be abandoned prematurely.

PMID- 15563332
TI  - Disruption of eye movements by ethanol intoxication affects perception of depth
      from motion parallax.
AB  - Motion parallax, the ability to recover depth from retinal motion generated by
      observer translation, is important for visual depth perception. Recent work
      indicates that the perception of depth from motion parallax relies on the slow
      eye movement system. It is well known that ethanol intoxication reduces the gain
      of this system, and this produces the horizontal gaze nystagmus that law
      enforcement's field sobriety test is intended to reveal. The current study
      demonstrates that because of its influence on the slow eye movement system,
      ethanol intoxication impairs the perception of depth from motion parallax.
      Thresholds in a motion parallax task were significantly increased by acute
      ethanol intoxication, whereas thresholds for an identical test relying on
      binocular disparity were unaffected. Perhaps a failure of motion parallax plays a
      role in alcohol-related driving accidents; because of the effects of alcohol on
      eye movements, intoxicated drivers may have inaccurate or inadequate information
      for judging the relative depth of obstacles from motion parallax.

PMID- 15563333
TI  - Object updating and the flash-lag effect.
AB  - Flash lag is a misperception of spatial relations between a moving object and a
      briefly flashed stationary one. This study began with the observation that the
      illusion occurs when the moving object continues following the flash, but is
      eliminated if the object's motion path ends with the flash. The data show that
      disrupting the continuity of the moving object, via a transient change in size or
      color, also eliminates the illusion. We propose that this is because a large
      feature change leads to the formation of a second object representation. Direct
      evidence for this proposal is provided by the results for a corollary perceptual
      feature of the disruption in object continuity: the perception of two objects,
      rather than only one, on the motion path.

PMID- 15563334
TI  - Probing the psychophysiology of the airways: physical activity, experienced
      emotion, and facially expressed emotion.
AB  - This article reviews research on airway reactivity in health and asthma within a
      psychophysiological context, including the effects of physical activity, emotion
      induction, and manipulation of facial expression of emotion. Skeletal muscle
      activation leads to airway dilation, with vagal withdrawal being the most likely
      mechanism. Emotional arousal, in particular negative affect, leads to airway
      constriction, with evidence for a vagal pathway in depressive states and
      ventilatory contributions in positive affect. Laboratory-induced airway responses
      covary with reports of emotion-induced asthma and with lung function decline
      during negative mood in the field. Like physical activity, facial expression of
      emotion leads to airway dilation. However, these effects are small and less
      consistent in posed emotional expressions. The mechanisms of emotion-induced
      airway responses and potential benefits of emotional expression in asthma deserve
      further study.

PMID- 15563335
TI  - Detection of synchronized oscillations in the electroencephalogram: an evaluation
      of methods.
AB  - The signal averaging approach typically used in ERP research assumes that peaks
      in ERP waveforms reflect neural activity that is uncorrelated with activity in
      the ongoing EEG. However, this assumption has been challenged by research
      suggesting that ERP peaks reflect event-related synchronization of ongoing EEG
      oscillations. In this study, we investigated the validity of a set of methods
      that have been used to demonstrate that particular ERP peaks result from
      synchronized EEG oscillations. We simulated epochs of EEG data by superimposing
      phasic peaks on noise characterized by the power spectrum of the EEG. When
      applied to the simulated data, the methods in question produced results that have
      previously been interpreted as evidence of synchronized oscillations, even though
      no such synchrony was present. These findings suggest that proposed analysis
      methods may not effectively disambiguate competing views of ERP generation.

PMID- 15563336
TI  - The effect of erroneous responses on response monitoring in patients with major
      depressive disorder: a study with event-related potentials.
AB  - Perceived failure is reported to have detrimental effects on subsequent
      performance in patients with major depressive disorder. We investigated the error
      related negativity (ERN)/error negativity (Ne), an electrophysiological correlate
      of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV
      major depressive disorder and 16 matched controls participated in an Eriksen
      flanker task with continuous performance feedback that signaled monetary reward.
      Compared to controls, patients with major depressive disorder showed a less
      negative ERN/Ne in error trials following error trials. This result might reflect
      impaired response monitoring processes in major depressive disorder resulting
      from an underactivity in a central reward pathway and/or a deficit in strategic
      reasoning.

PMID- 15563337
TI  - P300 amplitude in nonalcoholic adolescent twin pairs who become discordant for
      alcoholism as adults.
AB  - Past reports suggest that reduced P300 amplitude is associated with risk for
      alcoholism. We examined whether visual P300 amplitude could identify familial
      risk for alcohol disorders in individuals not known to be at risk at the time
      P300 was recorded. These individuals were twins from pairs where neither twin had
      an alcohol disorder at age 17 but familial risk was established at age 20 when
      one twin developed an alcohol disorder whereas the other did not. Of special
      interest was the P300 of the unaffected twin recorded at age 17 when both twins
      were alcoholism free. We found reduced P300 in the unaffected twin compared to
      pairs where both members were continuously disorder free. Hence, P300 was reduced
      in alcohol disorder-free individuals whose twin siblings subsequently developed
      alcoholism, further supporting reduced P300 amplitude as an endophenotype
      indexing familial risk for alcoholism.

PMID- 15563338
TI  - The application of jackknife-based onset detection of lateralized readiness
      potential in correlative approaches.
AB  - The onset of the lateralized readiness potential (LRP) represents an interesting
      parameter within mental chronometry. According to Miller, Patterson, and Ulrich
      (1998), reliability increases when LRP onsets are detected in jackknifed LRP
      waveforms. Until now, jackknifed LRP onsets could be analyzed in factorial
      designs only. The aim of the present study was to extend the application of
      jackknifing to correlative approaches (e.g., in personality research). Using
      different onset scoring techniques, in several simulations run on realistic LRP
      data jackknifing and single-subject procedures were compared regarding their
      estimates of a simulated true correlation. For all scoring techniques but
      regression, jackknifed coefficients were on average higher than the respective
      single-subject coefficients, and statistical power was higher. Overall, combining
      jackknifing with a 50%-relative onset criterion is recommended.

PMID- 15563339
TI  - Current-source density analysis of slow brain potentials during time estimation.
AB  - Two event-related potential studies were conducted to investigate differential
      brain correlates of temporal processing of intervals below and above 3-4 s. In
      the first experiment, 24 participants were presented with auditorily marked
      target durations of 2, 4, and 6 s that had to be reproduced. Timing accuracy was
      similar for all three target durations. As revealed by current-source density
      analysis, slow-wave components during both presentation and reproduction were
      independent of target duration. Experiment 2 examined potential modulating
      effects of type of interval (filled and empty) and presentation mode (randomized
      and blocked presentation of target durations). Behavioral and slow-wave findings
      were consistent with those of Experiment 1. Thus, the present findings support
      the notion of a general timing mechanism irrespective of interval duration as
      proposed by scalar timing theory and pacemaker-counter models of time estimation.

PMID- 15563340
TI  - Long-term exposure to noise impairs cortical sound processing and attention
      control.
AB  - Long-term exposure to noise impairs human health, causing pathological changes in
      the inner ear as well as other anatomical and physiological deficits. Numerous
      individuals are daily exposed to excessive noise. However, there is a lack of
      systematic research on the effects of noise on cortical function. Here we report
      data showing that long-term exposure to noise has a persistent effect on central
      auditory processing and leads to concurrent behavioral deficits. We found that
      speech-sound discrimination was impaired in noise-exposed individuals, as
      indicated by behavioral responses and the mismatch negativity brain response.
      Furthermore, irrelevant sounds increased the distractibility of the noise-exposed
      subjects, which was shown by increased interference in task performance and
      aberrant brain responses. These results demonstrate that long-term exposure to
      noise has long-lasting detrimental effects on central auditory processing and
      attention control.

PMID- 15563341
TI  - Posterior brain ERP patterns related to the go/no-go task in children.
AB  - Event-related potentials (ERPs) and performance correlates of inhibition of
      responses to no-go stimuli were investigated in 6-12-year-old children and young
      adults. The percent of correct responses to go stimuli was high and similar in
      both groups; the percent of false alarm errors to no-go was significantly higher
      in children. Effective inhibition of responses to no-go stimuli was elucidated by
      a negative component of ERPs, the frontal-central N2, with peak latency 230-430
      ms after stimulus onset. In adults, N2 was larger to no-go than to go stimuli,
      regardless of stimulus frequency. This effect was more prominent in tasks with
      high (25% no-gos and 75% gos), than with low (75% no-gos and 25% gos) inhibitory
      demand. In children, the parietal N2 was generally larger to rare than to
      frequent stimuli, and it was more specifically related to inhibition. The
      analysis of the relationship of no-go N2 to the inhibitory content of stimuli,
      probability of stimuli, and the contextual task difficulty suggests that
      child/adult differences in behavioral responses and ERPs may be related to both
      the immaturity of the fronto-parietal cortical-cortical network and to different
      task strategies.

PMID- 15563342
TI  - Autonomic response patterns observed during the performance of an attention
      demanding task in two groups of children with autistic-type difficulties in
      social adjustment.
AB  - Two groups of children with autistic-type behavior problems were compared to a
      group of normal children with respect to their autonomic response patterns
      observed during the performance of an attention-demanding task. Heart rate, blood
      pressure, and respiratory activity were measured during periods of rest and of
      task performance. Applying a quantitative model of the baroreflex, we were able
      to demonstrate qualitative differences among the groups with respect to their
      vagally controlled response patterns, whereas sympathetic responsiveness did not
      differ. In terms of our model, the groups with autistic-type behavior showed a
      decrease in central vagal tone during task performance, while vagal gain appeared
      to be unaffected or even increased. In contrast, the children in the control
      group showed the expected pattern of a decrease in vagal gain while vagal tone
      appeared to be increased. Implications of our findings are discussed in the light
      of Damasio's somatic marking hypothesis.

PMID- 15563343
TI  - Cognitive performance and cerebral blood flow in essential hypotension.
AB  - In the present study cerebral blood flow was assessed in 40 subjects with
      chronically low blood pressure and 40 normotensive controls at resting conditions
      and during the execution of a cued reaction time task. Blood flow velocities were
      recorded by means of transcranial Doppler sonography in both middle cerebral
      arteries. In hypotensives flow velocity at rest was reduced bilaterally. During
      the anticipation of the stimuli, which the subjects had to respond to, a
      predominantly right hemispheric increase of flow velocity was observed in both
      groups. This increase was significantly less pronounced in the hypotensive group.
      Hypotensives showed longer reaction times, and there was a negative correlation
      between the extent of the flow velocity increase and the reaction times. This
      study is the first to demonstrate a reduced cerebral perfusion and maladaption of
      blood flow to cognitive demands due to essential hypotension.

PMID- 15563344
TI  - Hemodynamic effects of dietary caffeine, sleep restriction, and laboratory
      stress.
AB  - This study examined the separate and interactive effects of caffeine, sleep
      restriction, and task-induced laboratory stress in 96 healthy male and female
      volunteers. Participants alternated weekly between ingesting placebo and caffeine
      (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested
      or sleep restricted. Finapres measurements of blood pressure, cardiac output, and
      total peripheral resistance showed that caffeine produced persistent blood
      pressure increases with a vascular hemodynamic profile. Sleep restriction
      produced a pronounced vascular response not associated with appreciable changes
      in blood pressure, whereas blood pressure increases induced by cognitive activity
      showed mixed cardiac and vascular responses. The findings suggest that life-long
      dietary caffeine may contribute significantly to the development of
      cardiovascular disease.

PMID- 15563345
TI  - Cardiovascular reactivity and adaptation to recurrent psychological stress:
      replication and extension.
AB  - We analyzed the effects of evaluative observation and baseline duration on
      cardiovascular reactivity and adaptation to recurrent psychological stress.
      Cardiovascular reactivity to mental arithmetic stress was assessed in college men
      and women (N=224) during two pretest tasks, a test task, and a posttest task.
      Participants were assigned randomly in a 2 x 2 design to manipulations of
      baseline duration before the test task (4 min vs. 12 min) and evaluative
      observation during the test task (observed vs. control). Repeated exposure to
      stress attenuated cardiac but not vascular reactivity. Evaluative observation
      disrupted cardiac adaptation, resulting in a resurgence of beta-adrenergic
      cardiac reactivity during the test task. Cardiac adaptation resumed fully during
      the posttest task. Baseline duration had no effect on reactivity. The results
      replicate and extend previous work, and support the dual process theory of
      habituation and sensitization.

PMID- 15563346
TI  - Emotional specificity of startle potentiation during the early stages of picture
      viewing.
AB  - Potentiation of the startle blink reflex shortly after picture onset has only
      been reported in a sample of high animal-fear participants during fear-evoking
      stimuli. The experiment tested the emotional specificity of startle reflex
      modification at early (300 ms) and late (2-5 s) stages of picture viewing in an
      unselected sample (n=55). Participants viewed two negative picture categories,
      threat and disgust contents, in addition to neutral and positive pictures. Blink
      potentiation occurred for threat contents at both probe times, relative to
      neutral responses. Disgust contents only potentiated blinks relative to positive
      content responses. These results are inconsistent with a basic, prepulse
      interpretation of early startle modification and suggest that affective
      modification can be observed shortly after picture onset, depending on the
      specific emotional content of the picture.

PMID- 15563347
TI  - The cardiac cycle time effect revisited: temporal dynamics of the central-vagal
      modulation of heart rate in human reaction time tasks.
AB  - Lacey and Lacey (1974) suggested that during reaction time tasks higher brain
      centers dynamically adjust efferent vagal nerve pulses to the sino-atrial node of
      the heart, inducing phase-dependent heart rate changes. Since then, animal and
      human neuro-physiological results have provided evidence for this hypothesis.
      Higher subcortical and cortical brain centers may have reciprocal interactive
      pathways relating to autonomic control comparable to those at the level of
      peripheral autonomic changes and brain stem reflexes. In humans such central
      effects may be observed in the short latency vagal control of heart rate that has
      been studied mostly in reaction time (RT) tasks. RT task parameters modulate
      vagal pulses to the cardiac sino-atrial node (SAN), which in turn exerts a phase
      dependent change in the ongoing cardiac interbeat interval. Simulations of human
      RT task effects in an animal model of heart rate change support this hypothesis.
      The current study examined evidence for vagal control of three human phasic heart
      rate responses in RT tasks. The evidence indicates that the initiation of an RT
      response triggers a reflexive shift from vagal activation to vagal inhibition.
      This shift is cardiac cycle phase dependent. Graded anticipatory cardiac
      deceleration during the warning interval of an RT task varies with task relevance
      and time uncertainty. This response may be part of a control process engaged in
      time keeping. Hence, temporal variables mediate the central-autonomic-vagal
      modulation of heart rate.

PMID- 15563348
TI  - Effects of arousal and natural baroreceptor activation on the human muscle
      stretch reflex.
AB  - The nociceptive flexion reflex is inhibited during systole; this inhibition may
      be due to increased baroreceptor stimulation. It is yet to be determined whether
      other spinal reflexes are similarly modulated across the cardiac cycle. There is
      also evidence that stretch and tendon reflexes are facilitated by increased
      arousal. This study investigated the effects of phase of the cardiac cycle and
      arousal on the muscle stretch reflex components M1, M2, and M3. Stretch reflexes
      were elicited in leg muscles at six intervals across the cardiac cycle during
      rest, number repetition, and mental arithmetic. Mental arithmetic provoked
      increased cardiovascular arousal and facilitated both M1 and M2 compared to rest
      and number repetition. The stretch reflex did not vary with the phase of the
      cardiac cycle. While the stretch reflex is susceptible to arousal, natural
      baroreceptor-mediated modulation across the cardiac cycle may be specific to
      nociception.

PMID- 15563349
TI  - Introducing a baroreflex model for studying cardiovascular effects of mental
      workload.
AB  - A quantitative baroreflex control model is presented aimed at estimating
      differences in autonomic activation due to mental task performance. The model,
      which builds on earlier work of Wesseling and colleagues, is strongly supported
      by well-established knowledge of physiological control processes. Spectral
      measures of heart rate and blood pressure variability provide the information to
      estimate autonomic gain and tone parameters. The article gives a detailed model
      description as well as an evaluation in terms of spectral variability
      distributions, respiratory sinus arrhythmia, and vagal control mechanisms. The
      estimation procedure is outlined while presenting two studies that describe the
      effects of mental workload and vagal blockade, respectively. It is concluded
      that, using the model approach, cardiovascular effects of mental task performance
      can be interpreted in terms of specific changes in autonomic state. The model is
      implemented in a Matlab/Simulink environment and is available for other
      researchers in the field.

PMID- 15563350
TI  - Electrodermal reactivity and its association to substance use disorders.
AB  - Poor electrodermal response modulation is associated with substance use
      disorders, but the specificity of the relationship has not been tested. To test
      this, 112 college students were assessed for psychiatric symptoms using
      structured interviews and for ability to modulate skin conductance responses to 2
      s 92- or 110-dB white noise blasts that varied in temporal predictability. Twenty
      eight good and 28 poor modulators were compared on symptoms of alcohol and
      illicit drug use disorders, personality disorders (antisocial, borderline,
      histrionic, and narcissistic), social and specific phobia, and depression. As
      expected, poor modulators had significantly more symptoms of substance use
      disorders than good modulators. Groups did not differ in symptoms of anxiety
      disorder, depression, or personality disorders marked by disinhibition. Poor
      electrodermal response modulation may reflect a biological risk factor for
      substance use disorders in particular.

PMID- 15563354
TI  - The changing scene of the regulation of medicines in the UK. Paper from The Use
      of Medicines: Regulation & Clinical Pharmacology in the 21st Century Symposium -
      December 2003.
AB  - The Medicines and Healthcare products Regulatory Agency was established in April
      2003 by the merger of the Medicines Control Agency (MCA) and the Medical Devices
      Agency (MDA). This paper describes the scientific and organizational basis for
      the merger and describes the various challenges facing this new Agency.

PMID- 15563355
TI  - NICE and the public health.

PMID- 15563356
TI  - Risk:benefit assessment of old medicines.
AB  - Any meaningful discussion about the present value of old drugs requires
      appropriate comparisons with new drugs. While there is noisy propaganda claiming
      the superiority of new drugs, the evidence supporting these claims is often
      scanty and poor. Therefore, the database utilizable to evaluate old and new drugs
      is incomplete and fragile. There are several reasons, including the poor dossiers
      presented for the approval of new drugs, the lack of comparisons aimed at showing
      superiority of new drugs, the bias frequently involved in clinical trials and the
      conflict of interests. This brief discussion reviews these questions and gives
      some examples by comparing diuretics and new antihypertensive agents, ticlopidine
      and clopidogrel, and atypical and classical antipsychotic agents.

PMID- 15563357
TI  - Current approaches to prevent NSAID-induced gastropathy--COX selectivity and
      beyond.
AB  - Gastrointestinal (GI) toxicity associated with nonsteroidal anti-inflammatory
      drugs (NSAIDs) is still an important medical and socio-economic problem--despite
      recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three
      strategies are followed in clinical routine: (i) coprescription of a
      gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii)
      eradication of Helicobacter pylori. Proton pump inhibitors are the comedication
      of choice as they effectively reduce gastrointestinal adverse events of NSAIDs
      and are safe even in long-term use. Co-medication with vitamin C has only been
      little studied in the prevention of NSAID-induced gastropathy. Apart from
      scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells,
      a protective enzyme with antioxidant and vasodilative properties. Final results
      of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm
      about the GI safety of selective COX-2 inhibitors, especially in patients
      concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori
      increases the risk for ulcers particularly in NSAID-naive patients and therefore
      eradication is recommended prior to long-term NSAID therapy at least in patients
      at high risk. New classes of COX-inhibitors are currently evaluated in clinical
      studies with very promising results: NSAIDs combined with a nitric oxide
      releasing moiety (NO-NSAID) and dual inhibitors of COX and 5-LOX. These drugs
      offer extended anti-inflammatory potency while sparing gastric mucosa.

PMID- 15563358
TI  - The use of pharmacokinetic and pharmacodynamic data in the assessment of drug
      safety in early drug development.
AB  - The pharmaceutical industry continues to look for ways to reduce drug candidate
      attrition throughout the drug discovery and development process. A significant
      cause of attrition is due to safety issues arising either as a result of animal
      toxicity testing or in the clinical programme itself. A factor in the assessment
      of safety during early drug development is the pharmacokinetic profile of the
      compound. This allows safety data to be considered in the light of systemic drug
      exposure and therefore permits a quantitative assessment. This is particularly
      applicable when assessing the risk of a new chemical entity (NCE) in relation to
      safety parameters such as QT interval prolongation, where free plasma
      concentrations have been shown to be predictive of this property in relation to
      potency in preclinical testing. Prior to actual human exposure it is therefore
      important to be able to predict reliably the pharmacokinetic behaviour of an NCE
      in order to place such safety findings into a quantitative risk context. The
      emerging science of pharmacogenetics is likely to further our ability to assess
      the risk of NCEs to populations and individuals due to genetic variance. The drug
      metabolizing enzyme CYP2D6 has been recognized as providing the potential to
      result in widely differing systemic drug exposure in the patient population due
      to polymorphic expression. Further knowledge is likely to add to our
      understanding of population differences in exposure and response and aid in the
      identification of risk factors. One potential strategy for improving the
      effectiveness of the drug discovery process is to obtain clinical pharmacokinetic
      data more rapidly in order to assess more accurately the potential for both
      efficacy and safety of an NCE. Whilst procedures and technologies are available
      that allow this on the microdose scale, it is important that we recognize
      potential limitations of these approaches in order that they can be applied
      beneficially.

PMID- 15563359
TI  - Subjective and physiological responses among racemic-methadone maintenance
      patients in relation to relative (S)- vs. (R)-methadone exposure.
AB  - AIMS: To investigate the possibility that (S)-methadone influences therapeutic
      and adverse responses to rac-methadone maintenance treatment, by examining how
      subjective and physiological responses among rac-methadone maintenance patients
      vary in relation to relative exposure to (S)- vs. (R)-methadone. METHODS: Mood
      states (Profile of Mood States), opioid withdrawal (Methadone Symptoms
      Checklist), physiological responses (pupil diameter, heart rate, respiration
      rate, blood pressure), and plasma concentrations (CP) of (R)- and (S)-methadone
      were measured concurrently 11-12 times over a 24-h interdosing interval in 55
      methadone maintenance patients. Average steady-state plasma concentrations
      (C(av)) and pharmacodynamic responses were calculated using area under the curve
      (AUC). Linear regression was used to determine whether variability in
      pharmacodynamic responses was accounted for by (S)-methadone C(av) controlling
      for (R)-methadone C(av) and rac-methadone dose. Ratios of (S)-:(R)-methadone
      using AUC(CP) and trough values were correlated with pharmacodynamic responses
      for all subjects and separately for those with daily rac-methadone doses > or =
      100 mg. RESULTS: (S)-methadone C(av) accounted for significant variability in
      pharmacodynamic responses beyond that accounted for by (R)-methadone C(av) and
      rac-methadone dose, showing positive associations (partial r) with the intensity
      of negative mood states such as Tension (0.28), Fatigue (0.31), Confusion (0.32),
      and opioid withdrawal scores (0.30); an opposite pattern of relationships was
      evident for (R)-methadone. The plasma (S)-:(R)-methadone AUC(CP) ratio (mean +/-
      SD 1.05 +/- 0.21, range 0.65-1.51) was not significantly related to
      pharmacodynamic responses for the subjects as a whole but showed significant
      positive associations (r) with the intensity of negative mood states such as
      Total Mood Disturbance (0.61), Tension (0.69), Fatigue (0.65), Confusion (0.64),
      Depression (0.49) and heart rate (0.59) for the > or = 100-mg dose range.
      CONCLUSIONS: These findings agree with previous evidence that (S)-methadone is
      associated with a significant and potentially adverse profile of responses
      distinct from that of (R)-methadone. Individual variability in relative (S)- vs.
      (R)-methadone exposure may be associated with variability in response to rac
      methadone maintenance treatment.

PMID- 15563360
TI  - A semimechanistic and mechanistic population PK-PD model for biomarker response
      to ibandronate, a new bisphosphonate for the treatment of osteoporosis.
AB  - AIMS: Ibandronate, a highly potent nitrogen-containing bisphosphonate, is the
      subject of an ongoing clinical development programme that aims to maximize the
      potential of simplified, less frequent oral and intravenous (i.v.) administration
      in osteoporosis. A modelling and simulation project was undertaken to
      characterize further the clinical pharmacology of ibandronate and identify
      convenient intermittent oral and i.v. regimens for clinical evaluation. METHODS
      AND RESULTS: Using selected data from clinical studies involving 174 women with
      postmenopausal osteoporosis (PMO), a classical multicompartmental pharmacokinetic
      pharmacodynamic (PK-PD) model was developed that accurately described the PK of
      i.v. ibandronate in plasma and urine and urinary excretion of the C-telopeptide
      of the alpha chain of type I collagen (uCTX), a sensitive biomarker of PD
      response to ibandronate. To reduce processing times, the classical PK-PD model
      was simplified using a "kinetics of drug action" or kinetic (K)-PD model (i.e. a
      dose-response model as opposed to a dose-concentration-response model). The
      performance of the K-PD model was evaluated by fitting data simulated with the PK
      PD model under various dosing regimens. The simplified model produced a virtually
      indistinguishable fit of the data from that of the PK-PD model. The K-PD model
      was extended to consider the influence of supplemental therapy (calcium with or
      without vitamin D) on the PD response and validated by retrospectively simulating
      the uCTX response in a prior Phase III and Phase II/III study of i.v.
      ibandronate, given once every 3 months, in 3380 women with PMO. The observed
      median uCTX responses at the scheduled assessment points in the completed studies
      were within the distribution of the simulated responses. The K-PD model for i.v.
      ibandronate was extended further to allow simultaneous fitting of uCTX responses
      after i.v. and oral administration in 676 postmenopausal women with osteoporosis,
      and validated by retrospectively simulating the data observed in a Phase I study
      of oral daily ibandronate in 180 women with PMO. The K-PD model adequately
      described the uCTX response after oral dosing. CONCLUSIONS: This validated K-PD
      model is currently being used to evaluate a range of novel intermittent oral and
      i.v. ibandronate regimens in an ongoing clinical development programme.

PMID- 15563361
TI  - Effect of efavirenz treatment on the pharmacokinetics of nelfinavir boosted by
      ritonavir in healthy volunteers.
AB  - AIMS: A once-daily (q.d.) nucleoside-sparing regimen can prevent mitochondrial
      toxicity, overcome viral resistance and improve compliance. In the present study
      the effect of efavirenz on the pharmacokinetics and tolerability of once-daily
      nelfinavir/ritonavir was evaluated in healthy subjects. METHODS: This was a
      multiple-dose, open-label, single-group, two-period study in 24 healthy subjects.
      Each received from days 1-10 (period 1): 1875 mg nelfinavir plus 200 mg ritonavir
      q.d. with a 300-kcal snack. During days 11-20 (period 2) efavirenz 600 mg q.d.
      was added to the regimen. Blood samples were collected up to 24 h after dosing on
      days 10 (period 1) and 20 (period 2). High-performance liquid chromatography
      methods were used for the determination of the concentrations of all compounds.
      The main pharmacokinetic parameters were calculated using noncompartmental
      methods. RESULTS: All subjects completed the study. After the first period mean
      nelfinavir AUC(0-24 h), C(max) and C(24) were 49.6 mg h(-1) l(-1), 5.0 mg l(-1)
      and 0.37 mg l(-1), and the sum of nelfinavir plus its active metabolite M8 C(24)
      was 0.83 mg l(-1). The relative bioavailability, expressed as a geometric mean
      ratio (90% confidence interval) for nelfinavir AUC(0-24 h), C(max) and C(24) of
      period 2 compared with period 1 was: 1.30 (1.21, 1.40), 1.29 (1.19, 1.40) and
      1.48 (1.32, 1.66). The sum of nelfinavir and M8 C(24) in period 2 was 0.99 mg l(
      1), an increase of 19%. No serious adverse events occurred. CONCLUSIONS: The
      studied regimens were well tolerated. Nelfinavir/ritonavir given together with
      efavirenz resulted in a 48% higher mean C(24) concentration for nelfinavir, and
      the sum of nelfinavir and M8 C(24) concentrations was 0.99 mg l(-1). Efavirenz
      exposure in this study was similar to that reported previously, and therefore can
      be used effectively in combination with ritonavir and nelfinavir.

PMID- 15563362
TI  - Influence of ketoconazole on azimilide pharmacokinetics in healthy subjects.
AB  - AIM: To assess the influence of ketoconazole on azimilide pharmacokinetics.
      METHODS: A two-period randomized crossover study was conducted in healthy male
      and female subjects (19-45 years). Placebo or 200 mg ketoconazole were
      administered orally every 24 h for 29 days. On day 8, a single oral dose of 125
      mg azimilide dihydrochloride was coadministered following an overnight fast.
      Blood samples were obtained prior to and for 22 days following azimilide
      dihydrochloride administration. The plasma protein binding of azimilide was also
      assessed at 6 h after dosing. RESULTS: Following ketoconazole administration, a
      16% increase in azimilide AUC (90% confidence interval (CI) 112%, 120%), a 12%
      increase in C(max) (95% CI 107%, 116%), a 13% increase in t(1/2,z) (95% CI 107%,
      120%) and a 14% decrease in CL(o) (95% CI 82%, 90%) were observed. CONCLUSIONS:
      The changes in azimilide pharmacokinetics following ketoconazole treatment are
      not clinically important since the 90% CI for the AUC fell within the
      prespecified range of 80-125%. Thus, no clinically important drug interactions
      are expected when azimilide dihydrochloride is coadministered with CYP3A4
      inhibitors.

PMID- 15563363
TI  - Medication reviews in the community: results of a randomized, controlled
      effectiveness trial.
AB  - AIMS: To examine the effectiveness of a multidisciplinary service model
      delivering medication review to patients at risk of medication misadventure in
      the community. METHODS: The study was carried out in three Australian states;
      Queensland, New South Wales and Western Australia, and conducted as a randomized,
      controlled effectiveness trial with the general practitioner (GP) as the unit of
      randomization. In total, 92 GPs, 53 pharmacists and 400 patients enrolled in the
      study. The multidisciplinary service model consisted of GP education, patient
      home visits, pharmacist medication reviews, primary healthcare team conferences,
      GP implementation of action plans in consultation with patients, and follow-up
      surgery visits for monitoring. Effectiveness was assessed using the four clinical
      value compass domains of (i) functional status, (ii) clinical outcomes, (iii)
      satisfaction and (iv) costs. The domains of functional status (assessed by the
      health-related quality of life measure SF-36 subscales) and clinical outcomes (as
      assessed by adverse drug events (ADEs), number of GP visits, hospital services
      and severity of illness) were measured at baseline and endpoint. Satisfaction was
      measured by success in implementation and by participant satisfaction at
      endpoint, and costs (as assessed using medication and healthcare service costs,
      less intervention costs) were measured preintervention and during the trial. In
      addition, process evaluation was conducted for intervention patients, in which
      problems and recommendations from the medication reviews were described. RESULTS:
      The model was successfully implemented with 92% of intervention GPs suggesting
      that the model had improved the care of participating patients, a view shared by
      94% of pharmacists. In addition, positive trends in clinical outcomes (ADEs and
      severity of illness) and costs (an ongoing trend towards reduction in healthcare
      service costs) were evident, although the trial was limited to a 6-month
      intervention time. No differences between intervention and control groups were
      identified for the health-related quality of life domain. The cost-effectiveness
      ratio for the intervention based on cost savings, reduced adverse events and
      improved health outcomes was small. The most common problems identified in the
      medication reviews were potential adverse drug reactions, suboptimal monitoring
      and adherence/lack of concordance issues. In total, 54.4% of recommendations were
      enacted, and 23.9% were implemented precisely as recommended in the medication
      review. Follow-up evaluation showed that 70.9% of actions had a positive outcome,
      15.7% no effect and 3.7% had a negative outcome. CONCLUSIONS: Most studies
      emphasize efficacy and the best achievable clinical outcomes rather than whether
      an intervention will be effective in practice. The current trial showed that
      three of the four domains in the clinical value compass showed trends of
      improvement or were indeed improved in the relatively short follow-up period of
      the trial, suggesting that a service based on this model could achieve similar
      benefits in practice. A domiciliary medication review programme similar to this
      model has now been implemented into national Australian practice, where GPs and
      pharmacists are reimbursed by the Australian government for the provision of
      these services.

PMID- 15563364
TI  - Prescribing for osteoporosis following the use of inhaled and oral
      glucocorticoids in general practice.
AB  - AIMS: Systemic absorption from inhaled glucocorticoids may lead to bone loss. We
      determined the extent to which their use alone and in addition to short courses
      of oral glucocorticoids was associated with increased prescribing for
      osteoporosis in a large general practice population. METHODS: In a cohort study
      with follow-up of co-prescribing of antiosteoporotic drug therapy in the Irish
      national prescribing database (1.1 million people over 16 years), we identified
      32 081 patients who received inhaled glucocorticoids alone during a 12-month
      period (following an identical lead-in period). We determined the odds ratio
      (OR), adjusting for age and gender for the co-prescription of bisphosphonates or
      other antiosteoporotic therapy with inhaled glucocorticoids by logistic
      regression. RESULTS: The adjusted OR (95% confidence interval) for co-prescribing
      of bisphosphonates and all inhaled glucocorticoids was 1.87 (1.71, 2.04); 1.58
      (1.41, 1.78) for inhaled beclomethasone, 2.11 (1.75, 2.54) for inhaled budesonide
      and 3.29 (2.65, 4.1) for inhaled fluticasone. The ORs were significantly
      increased when patients who also received oral glucocorticoids were included and
      greater still in those under 45 years: 14.03 (10.6, 18.6). The results remained
      significant when the effects of comorbidity were adjusted for. The odds of
      receiving bisphosphonate therapy increased linearly with increasing exposure to
      inhaled glucocorticoids during the study period. CONCLUSIONS: Treatment with
      inhaled glucocorticoids in general practice is associated with an increased risk
      of co-prescribing for antiosteoporotic therapy in a potency- and a dose-related
      manner. Exposure to a course of oral glucocorticoids doubles this risk. These
      results suggest that the systemic effects on bone mineral density from using
      inhaled glucocorticoids may be clinically relevant but may also reflect
      prescribers' concerns for the development of osteoporosis in these patients.

PMID- 15563365
TI  - Serotonin reuptake inhibitor induced sensory disturbances.
AB  - Serotonin reuptake inhibitor induced sensory disturbances are reported rarely in
      the literature. This case report describes numbness and dysmorphic symptoms in
      the upper facial area associated with fluoxetine. There is no previous report of
      such an adverse reaction with any serotonin reuptake inhibitor in the literature
      and this report is intended to draw attention towards these unusual adverse
      effects.

PMID- 15563366
TI  - A case report of rhabdomyolysis with pentamidine that prompted a retrospective
      evaluation of a pharmacovigilance tool under investigation.

PMID- 15563367
TI  - Multi-dosage vials, potential for overdose.

PMID- 15563368
TI  - Hypogeusia as an adverse reaction of phenytoin.

PMID- 15563371
TI  - A new mixture model approach to analyzing allelic-loss data using Bayes factors.
AB  - BACKGROUND: Allelic-loss studies record data on the loss of genetic material in
      tumor tissue relative to normal tissue at various loci along the genome. As the
      deletion of a tumor suppressor gene can lead to tumor development, one objective
      of these studies is to determine which, if any, chromosome arms harbor tumor
      suppressor genes. RESULTS: We propose a large class of mixture models for
      describing the data, and we suggest using Bayes factors to select a reasonable
      model from the class in order to classify the chromosome arms. Bayes factors are
      especially useful in the case of testing that the number of components in a
      mixture model is n0 versus n1. In these cases, frequentist test statistics based
      on the likelihood ratio statistic have unknown distributions and are therefore
      not applicable. Our simulation study shows that Bayes factors favor the right
      model most of the time when tumor suppressor genes are present. When no tumor
      suppressor genes are present and background allelic-loss varies, the Bayes
      factors are often inconclusive, although this results in a markedly reduced false
      positive rate compared to that of standard frequentist approaches. Application of
      our methods to three data sets of esophageal adenocarcinomas yields interesting
      differences from those results previously published. CONCLUSIONS: Our results
      indicate that Bayes factors are useful for analyzing allelic-loss data.

PMID- 15563372
TI  - Gait unsteadiness and fall risk in two affective disorders: a preliminary study.
AB  - BACKGROUND: In older adults, depression has been associated with increased fall
      risk, but the reasons for this link are not fully clear. Given parallels between
      major depression and Parkinson's disease, we hypothesized that major depression
      and related affective disorders would be associated with impairment in the
      ability to regulate the stride-to-stride fluctuations in gait cycle timing.
      METHODS: We measured stride-to-stride fluctuations of patients with two forms of
      mood disorders, unipolar major depressive disorder (MDD) and bipolar disorder,
      and compared their gait to that of a healthy control group. The primary outcomes
      were two measures of gait unsteadiness that have been associated with fall risk:
      stride time variability and swing time variability. RESULTS: Compared to the
      control group, the two patient groups tended to walk more slowly and with
      decreased swing time and increased stride time. However, none of these
      differences was statistically significant. Compared to the control group, swing
      time variability was significantly larger in the subjects with bipolar disorder
      (p < 0.0001) and in the subjects with MDD (p < 0.0004). CONCLUSIONS: Patients
      with MDD and patients with bipolar disorder display gait unsteadiness. This
      perturbation in gait may provide a mechanistic link connecting depression and
      falls. The present findings also suggest the possibility that measurement of
      variability of gait may provide a readily quantifiable objective approach to
      monitoring depression and related affective disorders.

PMID- 15563373
TI  - Density-independent population projection trajectories of chromosome-substituted
      lines resistant and susceptible to organophosphate insecticides in Drosophila
      melanogaster.
AB  - BACKGROUND: Seasonal fluctuations in susceptibility to organophosphate
      insecticides were observed in the Katsunuma population of Drosophila melanogaster
      for two consecutive years; susceptibility to three organophosphates tended to
      increase in the fall. To examine the hypothesis that variation in fitness among
      resistant and susceptible genotypes could trigger the change of genetic
      constitution within the fall population, we investigated density-independent
      population projection trajectories starting from single adult females with
      characteristics of chromosome-substituted lines resistant and susceptible to the
      three organophosphates. RESULTS: Density-independent population projection
      trajectories, expressed as the ratios of the number of each chromosome
      substituted line to that of line SSS, for which all chromosomes were derived from
      the susceptible line, showed significant declines in numbers with time for all
      the resistant chromosome-substituted lines. CONCLUSION: The declining tendency in
      the density-independent population projection trajectories of the resistant
      chromosome-substituted lines could explain the simultaneous decline in the levels
      of resistance to the three organophosphates, observed in the Katsunuma population
      in the fall.

PMID- 15563374
TI  - Vaccination with EphA2-derived T cell-epitopes promotes immunity against both
      EphA2-expressing and EphA2-negative tumors.
AB  - BACKGROUND: A novel tyrosine kinase receptor EphA2 is expressed at high levels in
      advanced and metastatic cancers. We examined whether vaccinations with synthetic
      mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce
      protective and therapeutic anti-tumor immunity. METHODS: C57BL/6 mice received
      subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs)
      pulsed with synthetic peptides recognized by CD8+ (mEphA2671-679, mEphA2682-689)
      and CD4+ (mEphA230-44) T cells. Splenocytes (SPCs) were harvested from primed
      mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against
      syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines
      to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v.
      injected B16-BL6) establishment/progression was then assessed. RESULTS:
      Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL
      responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin
      (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or
      EphA2-negative syngeneic tumors in both s.c. and lung metastasis models.
      CONCLUSIONS: These data indicate that mEphA2 can serve as an attractive target
      against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to
      impact EphA2-negative tumors such as the B16 melanoma may suggest that such
      beneficial immunity may be directed against alternative EphA2+ target cells, such
      as the tumor-associated vascular endothelial cells.

PMID- 15563375
TI  - HTLV-1 p30II: selective repressor of gene expression.
AB  - Human T-lymphotropic virus type-1 (HTLV-1) is a complex retrovirus that causes
      adult T-cell leukemia/lymphoma (ATL) and is implicated in a variety of lymphocyte
      mediated disorders. HTLV-1 pX ORF II encodes two proteins, p13II and p30II whose
      roles are beginning to be defined in the virus life cycle. Previous studies
      indicate the importance of these viral proteins in the ability of the virus to
      maintain viral loads and persist in an animal model of HTLV-1 infection.
      Intriguing new studies indicate that p30II is a multifunctional regulator that
      differentially modulates CREB and Tax-responsive element-mediated transcription
      through its interaction with CREB-binding protein (CBP)/p300 and specifically
      binds and represses tax/rex mRNA nuclear export. A new study characterized the
      role of p30II in regulation of cellular gene expression using comprehensive human
      gene arrays. Interestingly, p30II is an overall repressor of cellular gene
      expression, while selectively favoring the expression of regulatory gene pathways
      important to T lymphocytes. These new findings suggest that HTLV-1, which is
      associated with lymphoproliferative diseases, uses p30II to selectively repress
      cellular and viral gene expression to favor the survival of cellular targets
      ultimately resulting in leukemogenesis.

PMID- 15563376
TI  - A comparison of biologically variable ventilation to recruitment manoeuvres in a
      porcine model of acute lung injury.
AB  - BACKGROUND: Biologically variable ventilation (return of physiological
      variability in rate and tidal volume using a computer-controller) was compared to
      control mode ventilation with and without a recruitment manoeuvre - 40 cm H2O for
      40 sec performed hourly; in a porcine oleic acid acute lung injury model.
      METHODS: We compared gas exchange, respiratory mechanics, and measured
      bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant
      function. Lung injury was scored by light microscopy. Pigs received mechanical
      ventilation (FIO2 = 0.3; PEEP 5 cm H2O) in control mode until PaO2 decreased to
      60 mm Hg with oleic acid infusion (PaO2/FIO2 <200 mm Hg). Additional PEEP to 10
      cm H2O was added after injury. Animals were randomized to one of the 3 modes of
      ventilation and followed for 5 hr after injury. RESULTS: PaO2 and respiratory
      system compliance was significantly greater with biologically variable
      ventilation compared to the other 2 groups. Mean and mean peak airway pressures
      were also lower. There were no differences in cell counts in bronchoalveolar
      fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung
      injury scoring revealed no difference between groups in the regions examined. No
      differences in surfactant function were seen between groups by capillary
      surfactometry. CONCLUSIONS: In this porcine model of acute lung injury, various
      indices to measure injury or inflammation did not differ between the 3 approaches
      to ventilation. However, when using a low tidal volume strategy with moderate
      levels of PEEP, sustained improvements in arterial oxygen tension and respiratory
      system compliance were only seen with BVV when compared to CMV or CMV with a
      recruitment manoeuvre.

PMID- 15563377
TI  - The lack of public health research output from India.
AB  - BACKGROUND: Systematic assessment of recent health research output from India,
      and its relation with the estimated disease burden, is not available. This
      information would help understand the areas in health research that need
      improvement in India to enhance the health of India's population. METHODS: The
      health research output from India during 2002, which was accessible in the public
      domain, was assessed by searching PubMed and other internet health literature
      databases, and was related to the disease burden suggested by the Global Burden
      of Disease Study. The main outcome measures were number of health papers with
      abstracts in basic, clinical and public health sciences; quality-adjusted
      research output based on the impact factors of journals in which the papers were
      published; classification of papers in disease/condition categories and
      comparison of research output with the estimated disease burden in each category.
      Comparison of the health papers from India during 2002 included in PubMed was
      done with those from Australia during one quarter of 2002. RESULTS: Of the 4876
      health papers from India in 2002 in PubMed, 48.4%, 47.1% and 4.4% were in basic,
      clinical and public health sciences, respectively. Of the 4495 papers based on
      original research, only 3.3% were in public health. Quality-adjusted original
      research output was highest for non-communicable diseases (62% of total). Of the
      total quality-adjusted original research output, the proportions in injuries
      (0.7%), cardiovascular diseases (3.6%), respiratory infections (0.2%), diarrhoeal
      diseases (1.9%), perinatal conditions (0.4%), childhood cluster diseases (0.5%),
      unipolar major depression (0%), and HIV/AIDS (1.5%) were substantially lower than
      their proportional contribution to the disease burden in India. Human resources,
      health policy, health economics, and impact assessment of interventions were
      particularly poorly represented in public health research. The Australia-India
      ratio for quality-adjusted health research output per unit gross domestic product
      was 20 and for public health research output was 31. CONCLUSIONS: Good-quality
      public health research output from India is grossly inadequate, and strategic
      planning to improve it is necessary if substantial enhancement of population
      health were to be made possible. There is inordinately low relative research
      output in several diseases/conditions that cause major disease burden in India.

PMID- 15563380
TI  - Floating-toe deformity as a complication of the Weil osteotomy.
AB  - BACKGROUND: The Weil osteotomy for treatment of central metatarsalgia is an
      oblique osteotomy of the metatarsal neck and shaft parallel to the ground that
      provides controlled shortening of the metatarsal without additional depression.
      It offers many advantages over more traditional osteotomies, including stability
      and a large area of bone-to-bone contact. However, a floating-toe deformity
      appears to be a common complication after this osteotomy. METHODS: Between
      February, 2000 and February, 2003, 70 Weil osteotomies (in 26 patients) were done
      at one institution. Follow-up averaged 18.3 (6 to 36) months. Weightbearing
      radiographs were examined for shortening, subluxation, and for evidence of
      nonunion or malunion of the metatarsal head. Floating-toe deformity and mild
      recurrent tenderness were noted in the history and physical examination. The
      American Orthopaedic Foot and Ankle Society (AOFAS) Lesser Metatarsophalangeal
      Interphalangeal Scale (LMIS) was used for outcome rating. At final follow-up,
      nonunion and malunion also were evaluated. RESULTS: The median score of the AOFAS
      scale was 81 (19 to 95) points. Fifty-four percent of the osteotomies were done
      with a proximal interphalangeal (PIP) joint arthrodesis of the same ray, and we
      observed a higher occurrence of floating-toe deformity in this group of patients.
      CONCLUSION: Although it may be associated with some complications, the Weil
      osteotomy is an effective and safe procedure for the treatment of central
      metatarsalgia. We conclude that floating-toe deformity is a common complication
      associated with PIP joint arthrodesis. Although it appears not to cause a
      functional impairment, concurrent PIP arthrodesis should be avoided to reduce the
      occurrence of floating toes.

PMID- 15563381
TI  - Lisfranc fracture-dislocation in patients with multiple trauma: diagnosis with
      multidetector computed tomography.
AB  - BACKGROUND: We assessed acute phase multidetector computed tomography (MDCT)
      findings of Lisfranc fracture-dislocations in patients with multiple trauma
      referred to a Level I trauma center over a 29-month period. METHODS: Two hundred
      and eighty two patients (208 male and 74 female) between the ages of 13 and 89
      (mean 42) years had, at the request of emergency room physicians, MDCT of the
      foot and ankle after acute injury. RESULTS: A total of 21 Lisfranc fracture
      dislocations were found in 19 (7%) patients. Two main injury mechanisms were
      established: falling from high places in 10 injuries (48%) and traffic accidents
      in five (24%). Primary radiographs were available in 17 (81%) feet, and four
      (24%) had false negative radiographic results when compared to MDCT. In all
      Lisfranc fracture-dislocations MDCT showed the joint anatomy and the extent of
      dislocation better than primary radiographs, and in six (46%) of 13 true positive
      primary radiographs, MDCT revealed additional occult fractures in the Lisfranc
      joint. Multidetector CT revealed additional occult fractures in other parts of
      the foot and ankle in six (35%) of 17 feet. CONCLUSIONS: Standard radiography
      remains a primary diagnostic modality in acute foot and ankle trauma.
      Multidetector CT with high-quality multiplanar reconstruction (MPR) is
      recommended as a complementary examination in high-energy injury in patients with
      multiple trauma or in patients in whom radiographic images are equivocal. This
      may reveal Lisfranc fracture-dislocations, show the extent of the fracture
      dislocation, and reveal occult fractures in other parts of the foot and ankle.

PMID- 15563382
TI  - Surgical correction of crossover deformity of the second toe: a technique for
      tenodesis.
AB  - Twenty-seven patients with 30 crossover toe (COT) deformities of the second toe
      were evaluated. This deformity in the transverse and sagittal planes at the
      second metatarsophalangeal joint may be caused by hindfoot pronation. Compression
      of the lateral plantar nerve may produce incompetence of the second dorsal
      interosseous muscle and an increased extension-adduction pull by the lumbrical
      and first dorsal interosseous muscles. A surgical procedure for tenodesis is
      described to correct these deformities and restore the extrinsic-intrinsic
      musculotendinous balance at the second MTP joint. Our results are encouraging,
      with 83% good or excellent results. There was one recurrence.

PMID- 15563383
TI  - Variations in fibular position, talar length, and anterior talofibular ligament
      length.
AB  - BACKGROUND: Proprioceptive deficiencies, peroneal muscle weakness, varus
      hindfoot, and varus tibial plafond have each been implicated as a predisposing
      factor in recurrent ankle instability. Another predisposing factor for
      instability is a position of the fibula posterior to the transverse axis of the
      talus. This study examined the relationship of fibular position and ankle
      instability with anatomic dissection and magnetic resonance imaging (MRI).
      METHODS: Data were obtained from 100 consecutive MRI scans of adult ankles: the
      malleolar index in degrees and the fibular position anterior or posterior to the
      anteromedial malleolar plane and relative to the transverse axis of the talus.
      Twenty cadaver ankles also were studied by MRI and then by anatomic dissection.
      The malleolar index, the talar length, and the length of the anterior talofibular
      (ATF) ligament were recorded. RESULTS: The MRI study showed that variation of the
      malleolar index ranged from 2 to 30 degrees. There was no correlation between the
      malleolar index and the talar length or the length of the ATF ligament.
      CONCLUSIONS: There is a bell-shaped curve of variation of the position of the
      fibula relative to the transverse axis of the talus. An ankle mortise with a more
      posteriorly positioned fibula has less structural stability and is more
      susceptible to sprain. Neither talar length nor ATF ligament length correlated
      with fibular position.

PMID- 15563384
TI  - Osteochondromas of the talus presenting as intraarticular loose bodies: report of
      two cases.

PMID- 15563385
TI  - Ankle impingement: combined anterior and posterior impingement syndrome of the
      ankle.
AB  - BACKGROUND: Simultaneous anterior and posterior ankle impingement has not been
      previously reported. We identified 62 patients with both anterior and posterior
      impingement and report the results of anterior arthroscopic and posterior open
      treatment. METHODS: Between January, 1990, and December, 2003, 62 consecutive
      patients with symptoms and signs of both anterior and posterior impingement of
      the ankle were identified. Fifty-eight recorded a single injury or multiple ankle
      sprains. The most common mechanism of injury was inversion or plantarflexion.
      Initial conservative treatment failed in all patients and anterior arthroscopy
      and open posterior clearance were done. Followup averaged 11.4 months (up to 5
      years). All patients showed posttraumatic synovitis at arthroscopy, and 48 had
      other arthroscopically-detected lesions, such as anterior tibial plafond lesions,
      ossicles, or soft-tissue impingement. The posterior arthrotomy revealed a bony
      cause for impingement in all but four patients, usually an os trigonum or a long
      posterior process of the talus. RESULTS: Three patients had anterolateral
      tenderness after arthroscopy and three had tenderness of the posterior arthrotomy
      scar. There were no persistent neurologic complications. Fifty-eight patients
      were available for followup. Forty-seven (81%) had excellent or good outcomes,
      nine (15.5%) had fair outcomes, and two (3.5%) were graded as poor. CONCLUSION:
      Usually, anterior and posterior impingement occur separately; however, there are
      patients who have symptoms and signs of both anterior and posterior ankle
      impingement. A single inversion or plantarflexion mechanism of injury may be
      responsible for this syndrome, although it may also be caused by repetitive
      inversion injury. Combined anterior arthroscopic and posterior open treatment
      obtained good results with minimal complications and morbidity.

PMID- 15563386
TI  - The effect of ankle injury on subtalar motion.
AB  - BACKGROUND: Injuries to the medial and lateral ankle ligaments have been
      implicated in subtalar joint instability. Lateral injury increased subtalar joint
      varus and anterior translation, while deltoid injury increased external rotation
      and valgus in studies using static, non-physiologic testing. METHODS: The current
      study employed a physiologically accurate ankle model using phasic force-couples
      attached to the muscle-tendon units to reproduce ankle motion. Six-degree-of
      freedom kinematics of the tibia, talus, and calcaneus were measured using a VICON
      motion analysis system under the following experimental conditions: 1) intact
      ligaments 2) complete lateral ligament injury with subsequent repair, 3)
      superficial deltoid injury with subsequent repair, and 4) deep deltoid injury
      without repair in eight harvested lower extremities. Statistical analysis was by
      repeated measures analyses of variance. RESULTS: At heel-strike, the subtalar
      joint is in internal rotation, dorsiflexion, and varus. As the leg progresses to
      foot-flat, there is external rotation, plantarflexion, and valgus rotation. From
      foot-flat to heel-rise, there is little subtalar joint motion, while at toe-off,
      there is slight internal rotation, dorsiflexion, and varus rotation. The total
      rotations amounted to 9.0 degrees (SD 5.0 degrees) external rotation, 6.1 degrees
      (SD 2.5 degrees) plantarflexion, and 7.8 degrees (SD 5.5 degrees) valgus.
      Disruption of the superficial deltoid increased plantarflexion (p < .001) and
      valgus (p < .05). The additional lateral injury increased both external rotation
      (p < .001) and valgus (p < .02). Lateral injury alone had no significant effect
      on subtalar joint motion. CONCLUSION: Unlike most previous reports, this study
      showed no significant influence of isolated lateral ankle injury on subtalar
      joint motion, probably because the current study examined subtalar joint motion
      under physiologic loading and motion rather than by static stress testing. This
      calls into question the relevance of static stress testing to the in situ
      function of the subtalar joint. The increased external rotation and valgus seen
      with deltoid injury in the current study is consistent with previous reports.

PMID- 15563387
TI  - An anomalous muscle on the dorsomedial aspect of the foot (m. cuneo-naviculo
      fascialis): case report.

PMID- 15563388
TI  - Torsional strains in the proximal fifth metatarsal: implications for Jones and
      stress fracture management.
AB  - BACKGROUND: Reports of nonunion of proximal fifth metatarsal fractures treated by
      internal fixation indicate that current fixation methods do not always adequately
      address the stresses to which the bone is subjected during ambulation. In
      particular, the insertion sites of the peroneus brevis and peroneus tertius
      tendons on the fifth metatarsal suggest that their actions can impose torsional
      stresses on the areas of the bone in which Jones fractures and stress fractures
      occur. Intramedullary screw fixation, however, offers little resistance to
      rotation of the proximal and distal fragments relative to one another. METHODS:
      To determine the potential for the existence of torsional stresses in the fifth
      metatarsal during post-operative ambulation, a simplified cadaver model of single
      limb stance was used in which cadaver feet were subjected to concurrent axial and
      tendon forces while monitoring the outputs of stacked rosette strain gauges
      placed at the typical sites of Jones and stress fractures. Principal strain and
      shear strain magnitudes and directions were measured. RESULTS: The shear strain
      magnitudes and strain axis directions indicated the presence of torsional
      stresses in the underlying bone potentially capable of causing internal rotation
      of the proximal fragment relative to the distal end of the bone. CONCLUSIONS:
      This finding has implications for the treatment of both Jones fractures and
      stress fractures of the proximal fifth metatarsal. An internal fixation device
      that has the capability to resist torsion as well as tension and bending would
      appear optimal to treat these fractures.

PMID- 15563389
TI  - Personal gait satisfaction after displaced intraarticular calcaneal fractures: a
      2-8 year followup.
AB  - BACKGROUND: Patients' satisfaction with gait after calcaneal fracture has rarely
      been studied. The objective of this paper was to determine how patient
      demographics, fracture type and treatment affected gait satisfaction after
      displaced intraarticular calcaneal fractures. The design of the study is a
      prospective randomized trial performed in four Level I trauma centers. METHODS:
      Three hundred and nineteen patients with 351 radiographically proven displaced
      intraarticular calcaneal fractures (DIACF) were randomly assigned to open
      reduction and internal fixation (ORIF), or nonoperative treatment. A 2- to 8-year
      follow-up was obtained, with patients completing SF-36 and a validated visual
      analogue scale to assess personal gait satisfaction. The final joint positions
      were confirmed using plain radiographs and CT scans for both treatment arms.
      Examination using a one-way analysis-of-variance was performed to determine if
      statistical differences existed in personal gait satisfaction between the
      treatment arms. RESULTS: Personal gait satisfaction scores were not significantly
      different between those DIACF treated with ORIF and those treated nonoperatively
      at 2- to 8-year follow-up. In patients treated with ORIF, improved personal gait
      scores were reported in those who were younger than 30 years of age, were non
      WCB, had jobs requiring a moderate work-load before injury, and had Bohler angles
      restored to above 0 degrees. Factors not found to be significant in gait
      satisfaction included unilateral or bilateral calcaneal fractures, quality of
      initial reduction, and sex of the patient. CONCLUSIONS: Subcategories determined
      that younger patients who were self-employed and treated operatively had improved
      gait scores. Treatment (operative or nonoperative) of calcaneal fractures did not
      affect gait satisfaction according to patient outcome scores.

PMID- 15563390
TI  - The association between subtalar joint motion and outcome satisfaction in
      patients with displaced intraarticular calcaneal fractures.
AB  - BACKGROUND: There is a paucity of literature on the effect of calcaneal fractures
      on subtalar joint motion and patient satisfaction. The objective of this study
      was to determine the relationship between subtalar joint motion and outcome
      satisfaction in patients who had displaced intraarticular calcaneal fractures.
      The design of this study was a retrospective analysis from a randomized,
      controlled clinical trial. The setting was a Level I trauma center. METHODS: Of
      the 332 displaced intraarticular calcaneal fractures entered into the clinical
      trial and managed by the senior author, 244 fractures had subtalar joint motion
      measurements taken at least 12 weeks after fracture, and patient-oriented
      outcomes were reviewed at 2 years. Nonoperative treatment consisted of ice,
      elevation, and rest without closed reduction. In the operative group, an extended
      lateral approach was used with subchondral fixation, plating, and bone grafting
      when necessary. The Short Form 36 (SF-36), a validated visual analogue scale
      (VAS), and a gait analogue score measured patient satisfaction. Subtalar joint
      motion was recorded as percentages of the uninjured limb and grouped into
      quartiles. RESULTS: The VAS, SF-36 (p <.0001), and the gait satisfaction score (p
      <.05) all increased significantly with increasing subtalar joint motion.
      Satisfaction on the VAS and SF-36 was significantly related to subtalar joint
      motion for men (p <.0001) and in the age groups 30 to 39 (p <.001) and 40 to 49
      years (p <0.05). In non-Workman Compensation Board (WCB) clients, higher subtalar
      joint motion was significantly related to improved satisfaction on VAS and SF-36
      (p <.005). Patient satisfaction was significantly related to subtalar joint
      motion as measured by the VAS when patients reported pre-injury workloads of
      moderate (p <.05) or heavy (p <.01) regardless of whether they were treated
      operatively (p <.05) or nonoperatively (p <.0005). CONCLUSIONS: The amount of
      subtalar joint motion at least 12 weeks after displaced intraarticular calcaneal
      fracture is significantly related to patient satisfaction at 2 years regardless
      of the method of treatment.

PMID- 15563391
TI  - Traumatic dislocation of the first metatarsophalangeal joint with tibial sesamoid
      fracture: a case report.

PMID- 15563392
TI  - Simple bone cysts of the calcaneus: a report of five cases and a review of the
      literature.
AB  - BACKGROUND: Simple bone cysts of the calcaneus are relatively uncommon. There is
      no clear consensus on either their etiology or management. Pathological fractures
      of such cysts are exceptionally rare. MATERIALS AND METHODS: Five simple bone
      cysts of the calcaneus were present in three males and two females with an
      average age of 44 years. One patient presented with pain, three cysts were
      incidental findings on ankle radiographs, and one patient presented with a
      fracture after a significant fall. RESULTS: All five were managed nonoperatively
      and had satisfactory outcomes. CONCLUSIONS: A review the literature on the
      etiology and management of simple bone cysts of the calcaneus and the outcomes of
      these patients indicate that complications of these cysts are rare and
      nonoperative management is appropriate.

PMID- 15563393
TI  - Surgical tip: manipulation of closed pinning for intraarticular calcaneal
      fracture.

PMID- 15563394
TI  - Re: the association between diagnosis of plantar fasciitis and windlass test
      results.

PMID- 15563395
TI  - Chance and necessity do not explain the origin of life.
AB  - Where and how did the complex genetic instruction set programmed into DNA come
      into existence? The genetic set may have arisen elsewhere and was transported to
      the Earth. If not, it arose on the Earth, and became the genetic code in a
      previous lifeless, physical-chemical world. Even if RNA or DNA were inserted into
      a lifeless world, they would not contain any genetic instructions unless each
      nucleotide selection in the sequence was programmed for function. Even then, a
      predetermined communication system would have had to be in place for any message
      to be understood at the destination. Transcription and translation would not
      necessarily have been needed in an RNA world. Ribozymes could have accomplished
      some of the simpler functions of current protein enzymes. Templating of single
      RNA strands followed by retemplating back to a sense strand could have occurred.
      But this process does not explain the derivation of "sense" in any strand.
      "Sense" means algorithmic function achieved through sequences of certain decision
      node switch-settings. These particular primary structures determine secondary and
      tertiary structures. Each sequence determines minimum-free-energy folding
      propensities, binding site specificity, and function. Minimal metabolism would be
      needed for cells to be capable of growth and division. All known metabolism is
      cybernetic--that is, it is programmatically and algorithmically organized and
      controlled.

PMID- 15563396
TI  - Kinetics of Smac/DIABLO release from mitochondria during apoptosis of MCF-7
      breast cancer cells.
AB  - Smac/DIABLO, a pro-apoptotic protein released from mitochondrial intermembrane
      space during apoptosis, promotes caspase activation by IAPs neutralization. The
      kinetics and molecular mechanism of Smac/DIABLO release from mitochondria has
      remained obscure. Homeostatic confocal microscopy, for the first time, showed the
      precise kinetics of Smac/DIABLO release from mitochondria during CPT-induced
      apoptosis in living MCF-7 cells. The time pattern of Smac/DIABLO escape from
      mitochondria comprised two phases: the initial phase of gradual protein release,
      followed by the second phase of plateau, appearing after 24 min of cell exposure
      to the drug. A similar pattern was observed during oxidative stress. The dynamics
      of Smac/DIABLO redistribution was confirmed by different methods: traditional
      confocal microscopy, immunoelectron microscopy and laser scanning cytometry. The
      inhibition of m-calpain prevented Smac/DIABLO release from mitochondria, which
      confirmed the involvement of Bax in the process. Acquired results indicate that
      CPT treatment triggers Bax-dependent release of Smac/DIABLO from mitochondria
      simultaneously with the efflux of cytochrome c.

PMID- 15563397
TI  - Cell biology, chemogenomics and chemoproteomics.
AB  - The scientific techniques used in molecular biological research and drug
      discovery have changed dramatically over the past 10 years due to the influence
      of genomics, proteomics and bioinformatics. Furthermore, genomics and functional
      genomics are now merging into a new scientific approach called chemogenomics.
      Advancements in the study of molecular cell biology are dependent upon "omics"
      researchers realizing the importance of and using the experimental tools
      currently available to cell biologists. For example, novel microscopic techniques
      utilizing advanced computer imaging allow for the examination of live specimens
      in a fourth dimension, viz., time. Yet, molecular biologists have not taken full
      advantage of these and other traditional and novel cell biology techniques for
      the further advancement of genomic and proteomic-oriented research. The
      application of traditional and novel cellular biological techniques will enhance
      the science of genomics. The authors hypothesize that a stronger
      interdisciplinary approach must be taken between cell biology (and its closely
      related fields) and genomics, proteomics and bio-chemoinformatics. Since there is
      a lot of confusion regarding many of the "omics" definitions, this article also
      clarifies some of the basic terminology used in genomics, and related fields. It
      also reviews the current status and future potential of chemogenomics and its
      relationship to cell biology. The authors also discuss and expand upon the
      differences between chemogenomics and the relatively new term--chemoproteomics.
      We conclude that the advances in cell biology methods and approaches and their
      adoption by "omics" researchers will allow scientists to maximize our knowledge
      about life.

PMID- 15563398
TI  - Simultaneous detection of DNA synthesis, activation and cytokine secretion in
      collagen II (250-270)-activated T lymphocytes by flow cytometry.
AB  - T cell activation and secretion of cytokines from activated peripheral blood
      mononuclear cells (PBMC) in culture have traditionally been measured by 3H
      thymidine incorporation for assessment of cell proliferation. However, this
      method has many disadvantages that limit its usage in analyzing antigen-specific
      T responses, because of the low specific frequencies of the cells. Collagen II
      (250-270) may be an important autoantigen involved in the pathology of rheumatoid
      arthritis (RA). To further study the specific T cells response to CII 250-270, we
      developed an improved method for measuring lymphocyte proliferation and
      activation, and intracellular cytokine production, by flow cytometry at the
      single cell level. BrdU, an analog of thymidine, was incorporated into cellular
      DNA as a marker of individual cell proliferation. The cells were fixed and
      permeabilized, and a monoclonal antibody against BrdU conjugated with a
      fluorescent dye was used to measure BrdU incorporation. A Tris staining technique
      for the simultaneous determination of cell surface activation markers (CD69 or
      CD25) and intracellular cytokine production was also used and the parameters were
      assessed by 3-color flow cytometry. Optimal conditions were selected to improve
      the sensitivity and specificity of the assays. This method allowed simultaneous
      detection of lymphocytic DNA synthesis, phenotype analysis and cytokine
      production at the single cell level, and thus it may be a useful tool for
      analyzing immune responses.

PMID- 15563399
TI  - Impaired AP-1 dimers and NFAT complex formation in immature thymocytes during in
      vivo glucocorticoid-induced apoptosis.
AB  - Ca2+-regulated nuclear factor of activated T cell (NFAT) family members are
      transcription factors crucial for the expression of various cytokine and other
      immunoregulatory genes. Moreover, NFAT transcription factors are involved in the
      regulation of development, maturation and selection of thymocytes. Typically, the
      NFAT complex is made up of NFATc (NFATc1-4) protein and activator protein-1 (AP
      1) transcription factor. AP-1 is a dimer consisting of two Jun proteins
      (homodimers) or Jun and Fos proteins (heterodimers). We have previously reported
      that NFAT DNA-binding activity significantly decreases in the thymus during
      glucocorticoid-induced apoptosis. In this study, we demonstrate that the
      expression and phosphorylation status of the NFAT proteins do not change during
      glucocorticoid-induced apoptosis. This suggests that glucocorticoids do not
      disturb a signal transduction pathway leading to the activation of NFATc proteins
      in thymocytes. Although the levels of particular Jun and Fos proteins do not
      decrease after glucocorticoid administration, the formation or DNA-binding
      activity of some AP-1 dimers is specifically abolished. Thus, the observed
      inhibition of NFAT transcription factor activity during glucocorticoid-induced
      apoptosis is likely to be a consequence of this perturbation or the lack of a
      proper AP-1 component.

PMID- 15563400
TI  - Cytoskeletal actin degradation induced by lovastatin in cardiomyocytes is
      mediated through caspase-2.
AB  - The objective of this study was to test the hypothesis that cytoskeletal actin
      fragmentation is mediated through caspase-2, specifically examining the ability
      of a caspase-2 inhibitor to interfere with actin fragmentation, in comparison
      with a caspase-3 inhibitor. Cardiomyocytes were cultured from embryonic chick
      heart. The fine structural element of cellular F-actin was visualized by staining
      cardiomyocytes with NBD-phallacidin. Lovastatin induced a dramatic and
      concentration-dependent loss of intact F-actin. The selectivity of this effect of
      lovastatin was demonstrated by the absence of similar changes in F-actin when
      cardiomyocytes were treated with the apoptotic stimulus palmitate, the metabolism
      of which produces acetyl CoA, the early substrate of cholesterol synthesis,
      through the mevalonate pathway. FACS analysis of NBD-phallacidin-stained cells
      was used to quantify the amount of F-actin loss. Actin fragmentation produced by
      lovastatin was operative through a caspase-2 pathway, as the caspase-2 inhibitor,
      z-VDVAD-fmk, significantly blocked lovastatin-induced changes in F-actin, but the
      caspase-3 inhibitor, Ac-DEVD-CHO, did not. Interruption of the mevalonate pathway
      was in part responsible for lovastatin's action, as the downstream metabolite
      mevalonate partially reversed the effect of lovastatin on actin fragmentation.
      These data indicate a previously unrecognized link between cytoskeletal actin and
      caspase-2.

PMID- 15563401
TI  - Tra2betal regulates P19 neuronal differentiation and the splicing of FGF-2R and
      GluR-B minigenes.
AB  - The present study demonstrates that the expression of Tra2beta1 (Transformer 2
      beta1) proteins, an SR (serine/arginine rich) protein, is developmentally up
      regulated in a neural-specific pattern. The up-regulation is also observed in RA
      (retinoic acid) induced neural differentiation of P19 cells. Tra2betal proteins
      are located in the nuclei of P19 cells, which are consistent with its functional
      site as an SR protein. The over-expression of Tra2betal proteins promotes RA
      induced neuronal differentiation of P19 cells. In P19 cells, the splicing of FGF
      2R (fibroblast growth factor receptor 2) minigene produces the BEK form, while
      the alternative splicing of GluR-B (glutamate receptor subunit B) minigene
      generates two products, the Flop and the Truncated isoforms. Tra2betal inhibits
      the BEK splicing, but it promotes the Flop splicing. The results therefore
      suggest that Tra2betal is involved in the regulation of alternative splicing
      processes during neural development, peculiarly the splicing of FGF-2R and GluR-B
      genes. Both FGF-2R and GluR-B genes are known to play important roles in neural
      differentiation.

PMID- 15563402
TI  - Plasticity of rat bone marrow-derived 5-hydroxytryptamine-sensitive neurons:
      dedifferentiation and redifferentiation.
AB  - Inducing cellular dedifferentiation has been proposed as a potential method for
      enhancing endogenous regeneration in mammals. Here we demonstrate that phenotypic
      and functional neurons derived from adult rat bone marrow stromal stem cells
      (MSCs) can be induced to undergo dedifferentiation, then proliferation and
      redifferentiation. In addition to morphological changes and expression of
      neuronal markers, neuron-specific enolase and neurofilament H, functional
      differentiation was monitored by intracellular Ca2+ mobilization in response to a
      ubiquitous neurotransmitter, 5-hydroxytryptamine (5-HT) at different stages. The
      neurons derived from rMSCs were found to have increased 5-HT response. This 5-HT
      sensitivity could be reversed to basal level similar to that found in rMSCs when
      neurons, up to 3 days after neuronal induction, were induced to undergo
      dedifferentiation. Increase in 5-HT-induced Ca2+ mobilization was again observed
      when rMSCs derived from dedifferentiated neurons were induced to redifferentiate
      into neurons again. Variation in 5-HT1A receptor immunoreactivity was observed in
      stem cells, differentiated neurons, dedifferentiated neurons and
      redifferentiation neurons, consistent with their respective 5-HT sensitivity.
      These results suggest that adult bone marrow-derived 5-HT sensitive neurons are
      capable of dedifferentiation, then proliferation and redifferentiation,
      indicating their plasticity and potential use in treatment of neural degenerative
      diseases.

PMID- 15563403
TI  - Fifth dimension of life and the 4/5 allometric scaling law for human brain.
AB  - Brain cells are not spherical. The basal metabolic rate (B) of a spherical cell
      scales as B approximately r2, where r is the radius of the cell; that of a brain
      cell scales as B approximately r(d), where r is the characteristic radius of the
      cell and d is the fractal dimensionality of its contour. The fractal geometry of
      the cell leads to a 4/5 allometric scaling law for human brain, uniquely endowing
      humans with a 5th dimension and successfully explains why the scaling exponent
      varies during rest and exercise. A striking analogy between Kleiber's 3/4 law and
      Newton's second law is heuristically illustrated. A physical explanation is given
      for the 4th dimension of life for three-dimensional organisms and the 5th
      dimension for human brain.

PMID- 15563404
TI  - A DNA uptake-stimulating protein increases the antiproliferative effect of c-myb
      antisense oligonucleotide on leukemic cells.
AB  - Proliferation of HL-60 and MOLT4 leukemia cells was inhibited by a c-myb
      antisense oligonucleotide (ASO) in the presence of a DNA uptake-stimulating
      protein (DNA uptake-stimulating factor, DUSF). The inhibitory effect was very
      mild in the absence of DUSF. Sense oligonucleotides or DUSF, alone or in
      combination, were found to be ineffective. Cellular expression of the c-myb
      protein was significantly more inhibited by the c-myb ASO in the presence than in
      the absence of DUSF. In the presence of DUSF, c-myb protein practically
      disappeared from the nuclei of HL-60 and MOLT4 cells treated with the ASO. Thus,
      DUSF appears to effectively stimulate the uptake of c-myb ASO into tumor cells in
      vitro, augmenting its antiproliferative effect by decreasing c-myb expression.

PMID- 15563405
TI  - Identification and characterization of coiled body-like structures in pea (Pisum
      sativum L.).
AB  - Coiled bodies (CBs) are nuclear organelles which were considered as "universal"
      nuclear structures in eukaryotic cells, but the formation and function of CBs,
      especially in plant cells, remained unclear. In this article we reported that CBs
      in meristematic cells of pea are oval to round obstacles in nucleus and in
      adjacent to nucleolus, often have the same electron density with nucleolus. We
      found that CBs could be stained by the rRNP preference staining method, but no
      rDNA was detected in the structure. Furthermore, our results of immunoelectron
      microscopy showed that several processing factors, include fibrillarin, U3 snoRNA
      and ITS1, were present in CB. It seems probable that CBs is derived structurally
      from nucleolus and act as transport, storage and processing subnucleolar
      organelles.

PMID- 15563406
TI  - Influence of cytoplasmic deletions on the filopodia-inducing effect of syndecan
      3.
AB  - Syndecans, transmembrane heparan sulfate proteoglycans (HSPG), mediate cell-cell
      and cell-matrix adhesion thereby controlling cell movement and shape. Syndecan
      cytoplasmic domains are very short (ca. 30 amino acids) and divided into two
      constant regions (C1 and C2) separated by one variable (V) region. Here we
      attempted to map the cytoplasmic region responsible for the filopodia-inducing
      effect of syndecan-3. We found that only the C1-region was necessary for this
      effect. In addition, the deletion of the C2-region led to extensive membrane
      blebbing. Nevertheless, the elimination of the entire cytoplasmic region did not
      affect delivery of syndecan-3 to the plasma membrane. These results indicate that
      the different regions of syndecan-3 cytoplasmic domain have different functions
      probably by binding to distinct proteins.

PMID- 15563407
TI  - [The integrated management of childhood illness: Haiti's example].
AB  - Child health in developing countries is a public health priority both at the
      national and international level. The World Health Organization, UNICEF and other
      technical partners have developed The Integrated Management of Childhood Illness
      (IMCI) strategy to reduce child mortality and improve child health and
      development through a holistic approach. By the end of 2002, 109 countries among
      which 17 in the region of the Americas and Caribbean had adopted and implemented
      this strategy,. In this region, Haiti presents the highest mortality rate for
      under-fives. Every year, more than 138,000 children die of diseases such as
      malaria, pneumonia, diarrhea, measles and perinatal complications. Malnutrition
      contributes to a high percentage of these deaths. It is recognised that the
      mortality due to these diseases can be prevented. To fight this burden, Haiti
      officially adopted the IMCI strategy in 1997. The objectives of this paper are,
      after a general overview of the IMCI strategy, to describe Haiti's child health
      and analyse the achievements of the first steps of implementing the IMCI strategy
      in Haiti. The methodology used was a standardised literature review and a
      qualitative survey based on semi-structured interviews of national and local
      health authorities involved in the implementation of the IMCI strategy in Haiti.
      Main results show a limited impact of the first and second phase of
      implementation in the country. The key factors for this have been limited
      economical and human resources. A unequal distribution of existing resources
      between the different IMCI strategy components especially community and family
      practices, has limited adequate coverage. Isolated actions in favour of child
      health as well as a lack of co-ordinated interventions between the various actors
      have been among the barriers for an adequate implementation of this strategy. We
      recognise that the approach used here is not a formal evaluation on the
      implementation of IMCI in Haiti. Nevertheless, we hope this article will
      contribute to draw the attention of national and international public health
      decision-makers on the difficulties of implementing this strategy in Haiti and in
      this way, improve child health in the country.

PMID- 15563408
TI  - [Intestinal helminthiasis among school children: preliminary results of a
      prospective study in Agboville in Southern Cote d'Ivoire].
AB  - Intestinal helminthiasis affects the health and academic performance of children
      in developing countries. To highlight a few socio-economic factors that impact
      the presence and upholding of intestinal helminthiasis, a cohort study was
      performed from February to June 2001. This study took place in Agboville in
      Southern Cote d'Ivoire on 363 children, under the age of 15, regularly enrolled
      in school and selected by two-step clustered sampling. After the survey was
      completed, their stools were examined using 3 methods: direct exam, Kato's
      technique, and Graham's anal scotch-test. Infected students received an
      appropriate anti-helminthic treatment. After performing a test two weeks later, a
      new sample of 348 parasite-free children was made up and re-examined after three
      months, through the aforementioned techniques. In this sample, we assumed that
      students who were infested in the initial exam were "exposed", while those who
      were not infested in the first place were deemed to be "not exposed". The results
      showed that 135 students out of the 360 admitted for the first exam were
      infested; or a 37.5% of intestinal helminthiasis prevalence (IC95%=30.5-45). The
      prevalent parasite species were Necator americanus (15%), Trichuris trichiura
      (13.6%), Schistosoma mansoni (10%). Twenty-eight per cent of 135 infested
      students were infected by more than one parasite. After three months, the
      incidence rate of intestinal helminthiasis calculated out of the remaining 336
      students was 7.7% (IC95%=4.4-13.1). The likelihood of re-infestation amounted to
      3.4 (IC95%=1.5-7.3). The pattern of re-infestation rates according to socio
      economic factors differed from that of infested prevalence. The prevalent
      parasites in re-infested patients were Trichuris trichiura (16.3%), Schistosoma
      mansoni (12.5%). All intestinal nematodes and Schistosoma mansoni were observed.
      The most frequent parasites species where those transmitted cutaneously. The high
      re-infestation rate suggests that intestinal helminthiasis in this region affects
      roughly the same children. These results show the necessity to continue our
      investigations in order to highlight essential hygienic factors in our long-term
      fight against intestinal helminthiasis.

PMID- 15563410
TI  - [Evolution of the prevalence of Mansonia schistosomiasis in the district of Sao
      Luis do Maranhao (Brazil) between 1978 and 2001].
AB  - This is an approach on the prevalence of the Mansonia schistosomiasis in the city
      of Sao Luis, capital of the State of Maranhao, over the last 23 years, assessed
      in the face of the control actions implemented during this period. The research
      was performed through data obtained in the annual reports of the Fundacao
      Nacional de Saude (National Health Foundation) - FUNASA/MA, from 1978 to 2001.
      Fourteen locations have been selected as follows: Areinha, Barreto, Camboa,
      Coroadinho, Coroado, Diamante, Fe em Deus, Floresta, Matadouro, Monte Castelo,
      Pianco, Sao Francisco, Vila Embratel and Vila Passos, whose prevalence was
      >or=4%, in at least one year of the period studied. In the 1980s, the prevalence
      was higher. It has to be highlighted that in all locations the level of
      prevalence underwent important oscillations during the evaluation year. It is an
      active search for cases and positive treatment, as well as sanitation works,
      determined the drop of prevalence in most of the locations at the end of the last
      decade.

PMID- 15563411
TI  - [Meningococcal meningitis epidemics in Benin].
AB  - Epidemics of meningococcal meningitis are common in several African countries,
      including Benin. In northern Benin, part of the "meningitis belt", incidence has
      been increasing over the past decade, and lethality is high. The A and C
      serogroups are the primary causal agents. Recently, the appearance of the W135
      strain in bordering countries induced considerable fear and necessitated more
      rigorous epidemiological surveillance in the north. Little epidemiologic
      information on the course and trends of these epidemics is available. The goal of
      this article is to describe the pattern of these outbreaks in two northern
      districts -- Atacora and Donga -- based on a retrospective collection and
      analysis of data from 16 health centres over the four-year period of 1998 through
      2001. Crude incidence rates increased from 85 to 567 per 100,000 in Atacora and
      71 to 619 per 100,000 in Donga. The fatality rate is higher in Donga (3.1%) than
      Atacora (2.7%). The epidemic pattern is bimodal in Atacora and unimodal in Donga,
      although they appear to have a common source. Comparison of the trends in the two
      districts indicated no significant differences (p>0.05). The authors suggest that
      epidemiological data be collected and updated routinely, that vaccination against
      the A and C serogroups be reinforced while awaiting a vaccine against W135, and
      that epidemiological surveillance be intensified, in Donga and especially along
      the border area between Atacora and Togo.

PMID- 15563413
TI  - [Iodized salt in Cameroon].
AB  - The WHO program to combat iodine deficiency disorders (IDD) adopted in 1992
      required countries producing cooking and table salt to add 50-100 ppm of iodine
      to salt. This program was adopted in Cameroon, but problems remain in ensuring
      adequate conditioning of the iodized salt at the factories to maintain the iodine
      levels so that consumers take in the required quantity. This study collected and
      analyzed five groups of salt samples from three provinces of Cameroon. Each group
      included a specimen from its factory, wholesalers, retailers, and households.
      Iodine content was measured by the volumetric method. The results showed that
      iodine levels in salt decreased substantially between the factory and the
      consumer; percentages of iodine loss in these samples varied from 44.8% to 82.3%.
      Iodine levels were highest in fine-grained salt. Iodine concentration also
      decreases after storage, perhaps as a function of the type and duration of the
      storage, temperature, packaging material and presence of impurities in salt. This
      study shows that even salt with an initial high iodine concentration may reach
      consumers with insufficient levels for daily needs.

PMID- 15563414
TI  - [Assessment of the risk of tuberculosis among health care personnel in Meknes].
AB  - Tuberculosis has long been a concern for those responsible for the health of
      hospital personnel. Several studies of healthcare professionals who work in
      Morocco with patients with tuberculosis have shown annual incidence rates
      approximately ten times higher than those for the general population. This survey
      of the risk of tuberculosis among healthcare personnel (109 subjects with high
      and 118 with intermediate exposure to tuberculosis) and a control population (124
      teachers) showed a positive correlation between the diameter of the tuberculin
      induration and intensity of exposure (significant difference between the highly
      exposed versus those with intermediate or no exposure). The risk of occupational
      tuberculosis was greater among the highly exposed healthcare workers. The
      involvement of occupational medicine units in health training in national public
      health programs and especially in programs combating tuberculosis must be a high
      priority activity, because studies show that tuberculin conversion rates diminish
      significantly when programs of tuberculosis sensitization (information, education
      and communication), prevention (vaccination), and control (screening and
      treatment) are widely available to healthcare professionals, even those who have
      direct and constant with patients with tuberculosis.

PMID- 15563416
TI  - [Causes of encephalopathy: descriptive study at Abidjan (Cote-d'Ivoire)].
AB  - OBJECTIVE: Assess the etiology and course of cases of encephalopathy seen in the
      neurology department of the Cocody University Hospital in Abidjan (Cote
      d'Ivoire), a city of more than three million inhabitants. METHODS: Retrospective
      analysis of patients admitted to the hospital neurology unit from 1 December,
      1998, through 31 December, 2000; with a lesion of the brain, brainstem,
      cerebellum or meninges. Lesions were either confirmed by computed tomography or
      clinically obvious; MRI was unavailable. RESULTS: Overall, 1011 subjects met the
      inclusion criteria: 58% were male; their median age was 45 years (range: 1 to 93
      years); more than 40% were not working, and 92% had a medical history. The
      etiology was vascular (445), infectious (380) or undetermined (125); rare cases
      were degenerative (5) or traumatic (4). Of 35 cases of metabolic encephalopathy,
      half were associated with another etiology. Pathological confirmation of cerebral
      tumors (22) was unavailable. All cases of toxic encephalopathy (11) involved
      adults and alcohol. Global lethality was 26% and did not differ significantly
      according to whether or not the etiology was identified (26% vs 28.8%). Another
      13% were lost to follow-up (left without discharge), and 61% patients recovered
      and were discharged after a median hospitalization of 12.5 days. CONCLUSION: The
      proportion of cases with an undetermined etiology is worrisome. Better knowledge
      would be useful to develop indicators to evaluate improvements in the medical
      management of these diseases.

PMID- 15563417
TI  - [Placenta previa: maternal and fetal prognosis covering 128 consecutive cases
      from the Brazzaville University Hospital Center].
AB  - OBJECTIVES: The aim of this study was to determine the frequency of placenta
      previa (PP) in our hospital; to assess the maternal and fetal prognosis; to
      specify its location, the term at occurrence, and the mode of childbirth; and to
      propose preventive measures to improve its management. MATERIAL AND METHOD: This
      retrospective study covers a 5-year period from 1 January, 1998, to 31 December,
      2002, and 128 cases of PP at the maternity ward of the Brazzaville University
      Hospital Center. The frequency of this complication during the study period was
      0.6%; 54.6% of the women were 26-35 years old; most had two or more previous
      pregnancies (72.7%) and two or more previous deliveries (73.6%). The central
      (total) variant was most common (84.4%). Most children (71.9%) were born before
      term, and even more (85.2%) delivered by cesarean; 43.8% of the new-borns had 1
      min Apgar scores of at least 7; 53.1% weighed less than 2500 g at birth and 44.5%
      (57) were premature. The principal postpartum morbidity involved: endometritis, 3
      cases (2.3%); parietal suppuration after cesarean, 7 cases (5.5%); and maternal
      anemia, 11 cases (8.6%). There were also 7 (5.5%) still-births and 12 (9.4%)
      early neonatal deaths. Causes of neonatal death included cerebral distress,
      neonatal infection, and complications of Hirschprung disease. CONCLUSION: PP
      remains a serious disease of pregnancy. Improving the maternal and fetal
      prognosis requires intensification of antenatal consultations, ultrasound
      examinations that enable the location of placental insertion to be identified,
      and timely cesarean delivery once the infant is sufficiently mature.

PMID- 15563418
TI  - [Effects of physical activity on adipose tissue cellularity in premenopausal
      obese women in Benin].
AB  - The purpose of this article was to quantify the exercise load and investigate the
      influence of physical exercise on adipose tissue in obese women from Benin.
      Twelve subjects participated at the study. Six of the subjects trained three
      times a week for six months. Each training session lasted forty-five minutes. The
      remaining six women constituted the control group. Biopsy samples of adipose
      tissue were taken from the same site in the gluteal iliac region at the end of
      six months and analyzed by histochemistry and electron microscopy. The results
      showed that all subjects suffered from severe central obesity; lipid content and
      number of adipocytes were higher among the sedentary woman than among those who
      exercised. Intense exercise in the latter used more lipids than carbohydrates. We
      conclude that regular, supervised physical exercise reduces lipid levels and thus
      induces weight loss.

PMID- 15563419
TI  - [Knowledge, attitudes and practices regarding glaucoma in the urban and suburban
      population of Lome (Togo)].
AB  - PURPOSE: One of the main constraints in the prevention of blindness is the lack
      of awareness of people regarding eye diseases. This study was undertaken to
      determine the level of knowledge, the attitudes and practices regarding glaucoma
      in the population of Lome. METHODS: An interview using a questionnaire was
      conducted among an opportunistic sample of 767 people living in the capital city
      of Lome and in some of its suburbs. The interview targeted people aged 20 to 65
      years; the questions were either closed or open. The interviews were conducted
      either in French or in the local languages where needed and in the latter case
      with the help of a translator. Variables measured included education status,
      e.g., schooling years, economic status and professional situation. RESULTS: The
      knowledge of eye diseases accounted for 84% among the population studied; the
      most well-known being myopia, cataract, presbyopia, and glaucoma in decreasing
      order. Glaucoma was known by 228 people (29.7%) among whom 25% were aware of
      glaucoma blindness cases; 61.5% declared that glaucoma was a serious condition;
      4.4% admitted the use of traditional eye-healers; 56.1% were not confident in the
      local doctors for the treatment of glaucoma. CONCLUSION: The high proportion of
      people who are not confident in the capabilities of national doctors to
      efficiently treat glaucoma is worrying. This situation requires the set up of a
      rational national strategic action plan (e.g., health education) aimed at
      reducing the burden of glaucoma blindness in the country.

PMID- 15563420
TI  - [Systematic reviews and meta-analysis in laboratory medicine: principles and
      methods].
AB  - BACKGROUND: Systematic reviews and meta-analyses can help health-care
      professionals to base their decisions on the highest levels of evidence, and are
      therefore the cornerstone in practicing evidence-based medicine. In the field of
      diagnosis in general, and in laboratory medicine in particular, systematic
      reviews are scarcer, and often of lower quality than in other areas of medicine.
      AIM: To summarize the principles and methods that can be advised to perform
      systematic reviews of good quality in laboratory medicine. METHODS: A narrative
      review of the literature and discussions with members of the Committee on
      Evidence-Based Laboratory Medicine of the International Federation of Clinical
      Chemistry and Laboratory Medicine, in particular during our last three meetings,
      enabled us to adapt to laboratory medicine the methods which are currently being
      advocated to perform systematic reviews of good quality in other medical areas.
      RESULTS: The process of systematic reviewing consists of six key steps: 1)
      preparation: formulation of question(s); 2) systematic search of the literature;
      3) selection of primary studies; 4) critical appraisal of the quality of the
      selected literature; 5) extraction and synthesis of data; 6) interpretation. The
      main differences between systematic reviews of diagnostic interventions and those
      of therapeutic interventions bear on question formulation, the choice of study
      designs to be included or excluded, the assessment of study quality and the
      statistical methods used to combine their results. The quoted references will
      help interested readers to deepen by themselves the most technical or
      controversial points. CONCLUSION: In order to improve quality of care as well as
      the balance between benefits, harms and costs of practice, each recommendation in
      guidelines should be based on a systematic review. In addition, such reviews can
      help to better identify gaps in biomedical knowledge, and improve critical
      skills, education, and training of professionals. One can therefore reasonably
      expect that the current multiplication of systematic reviews in laboratory
      medicine will favor the diffusion of diagnostic technologies with the highest
      levels of proven efficacy and effectiveness, at the detriment of the others.

PMID- 15563421
TI  - [Contribution of molecular cytogenetics in the diagnosis of chromosomal
      abnormalities].
AB  - Molecular cytogenetic approaches based on fluorescence in situ hybridization
      (FISH) with chromosome-specific probes have been increased in recent years. They
      become a powerful tool for chromosomal diagnosis in prenatal, constitutional and
      cancers genetic disorders. In fact, various procedures are now available to rapid
      identification of numerical and structural chromosome aberrations that escape to
      conventional chromosome banding analysis. Here, contribution of molecular
      cytogenetic approaches for diagnosis of disease related chromosomal changes are
      presented and discussed.

PMID- 15563422
TI  - [Hodgkin's disease and Epstein-Barr virus].
AB  - Epstein-Barr virus (EBV) seems to use B cell normal differentiation pathways to
      establish and maintain a persistent infection. This process is effectively
      controlled by the immune system through the action of EBV-specific T lymphocytes,
      so that the lifelong chronic infection is free of complications for most
      individuals. EBV is, however, associated with several malignancies. 30-50% of
      Hodgkin's lymphomas (HL) are EBV-associated. In EBV-positive HL, the virus is
      localized to the tumor cells and is clonal. HL is characterized by a type II form
      of latency with viral antigen expression limited to EBNA1, LMP1 and LMP2. EBV
      positive HL is more frequent in childhood, in older patients and in mixed
      cellularity cases. EBV association may represent a poor prognosis factor in the
      elderly. The true contribution of EBV to the pathogenesis of HL remains
      uncertain, but EBV may provide to abnormal B cells survival signals protecting
      them from apoptosis. Finally, whatever the role that EBV plays in tumor
      development, the presence of viral antigens in the malignant cells may represent
      a target for new therapeutic strategies.

PMID- 15563423
TI  - [Molecular biology and hepatocellular carcinoma: current status and future
      prospects].
AB  - Hepatocellular carcinoma (HCC) is among the fifth most common cancers worldwide.
      Its incidence is still rising in part because of the high level of hepatitis C
      virus infection. Tumor markers currently used such as serum alpha-foetoprotein
      are not sufficient for diagnosis of the tumor and satisfying follow-up of the
      patients. Mechanisms of hepatocarcinogenesis ar not completely understood
      although several altered genes have been described in HCC. The genetic changes
      involved can be divided in at least 4 different pathways, each pathway
      contributing to a limited number of tumors. These are: 1) the p53 pathway
      involved in response to DNA damage, 2) the retinoblastoma pathway involved in the
      control of the cell cycle, 3) the transforming growth factor-beta (TGF-beta)
      pathway involved in growth inhibition, and 4) the Wnt pathway involved in cell
      cell adhesion and signal transduction. Alterations of the epigenetic regulation
      of gene expression have also been described. Evolution of molecular biology
      methods tends to the development of more global genomic approaches;
      microsatellite instability analysis, chromosomal instability analysis or gene
      expression profile analysis have been used to investigate HCC. Finally, attempts
      to develop molecular biomarkers based on peripheral blood analysis more easily
      accessible in clinical routine patients have also been developed.

PMID- 15563424
TI  - [Mastocytosis, classification, biological diagnosis and therapy].
AB  - In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the
      release of chemical mediators from MCs, the pathologic infiltration of neoplastic
      MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC
      infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis
      might regress spontaneously. Systemic mastocytosis (SM) is more frequently
      diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived
      myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the
      majority of such patients. The natural clinical course in SM is variable. Whereas
      most patients remain at the indolent stage for many years, some have aggressive
      SM (ASM) at diagnosis. Other patients have an associated clonal hematologic none
      MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant
      characterized by circulating MCs and fatal disease progression. Two important
      diagnostic clues in SM are an increased serum tryptase level and the presence of
      abnormal mast cells in the bone marrow. The current review provides an overview
      of mastocytosis and its subvariants, the new classification of these diseases, a
      practical guide for the biological diagnosis and advances and future directions
      in therapy of these pathologies.

PMID- 15563425
TI  - [Reference limits for urine sediments performed on Sysmex UF-50].
AB  - The Sysmex UF-50 is an automated flow cytometer for urine sediments analysis.
      Interpretation of the results needs establishment of reference limits for the
      different constituents measured. First of all, we checked precision of
      measurements and stability of urines during transportation. Then, urine samples
      from 4 to 95 year old subjects were examined with the UF-50, by visual microscopy
      and test strips. Distributions of results for erythrocytes, leukocytes,
      epithelial cells, casts, bacteria and conductivity were described in a sample of
      680 subjects (364 men and 316 women), with creatininemia below 140 micromol/L,
      consuming no drugs and for women without intra uterine device and apart from
      menstruation period. Then, the results were compared with those obtained in
      groups selected on microscopic analysis and test strip results. UF-50 sensitivity
      and specificity were 77.5% and 88% for 15 erythrocytes/microL in reference to
      microscopic urinalysis, they were 91.3% and 87.3% for 15 leucocytes/microL. The
      reference sample was defined with negative microscopic results. The upper
      reference limits (centile 97.5) were 16 red blood cells/microL for men 14.5 for
      women, 13.5 and 33 leucocytes/microL, 8 and 19 epithelial cells/microL, 1,3 and
      0,4 casts/microL, 5 500 et 7 700 bacteria/microL, 36,2 et 34,6 conductivity
      mS/cm. The Sysmex UF-50 is a suitable analyser for urinary sediments. Reference
      limits may be different from usual reference limits due to variability in
      performances of other methods.

PMID- 15563426
TI  - [Tobacco: a potential inductor of lipid peroxidation of the human spermatozoon
      membrane?].
AB  - OBJECTIVE: To determine the membrane lipid peroxidation of human spermatozoon in
      a cohort of smokers in comparison of never-smokers. MATERIALS AND METHODS:
      Malondialdehyde (MDA), a stable product of the membrane lipid peroxidation, was
      assessed in 25 smokers and in 17 never-smokers. In parallel, an evaluation of
      sperm characteristics was realized for all the studied patients. RESULTS: For the
      first time, between smokers and never-smokers, a significative increase of MDA
      concentrations was found by the U-Mann and Whitney test (0.118 +/- 0.176 vs
      0.0392 +/- 0.0117 nmol/10(6) spermatozoa), a decrease of the forward motility
      (grade A), (18 +/- 8 vs 25 +/- 8%) and total sperm count (265.56 +/- 186.96 x
      10(6) vs 399.30 +/- 322.23 x10(6)), and also an increase of tapering heads (6 +/-
      4 vs 2 +/- 2%) or morphological stress pattern cells (39 +/- 6 vs 24 +/- 5%). In
      the smokers group, negative significative correlations were found by the non
      parametric Spearman test between the MDA concentrations and the sperm count per
      mL (r=-0.767, p<0.001), the total sperm count (r=-0.656, p<0.001) and the
      percentage of normal morphology (r=-0.644, p<0.001). CONCLUSIONS: Given of
      deleterious effects of tobacco in a large panel of human cells and specially on
      the male gametes, the increase of spermatozoon membrane MDA concentrations and
      the sperm abnormalities found in the group of smokers may be linked to cigarette
      smoking.

PMID- 15563427
TI  - [Human papillomavirus detection by the hybrid capture II assay with the liquid
      cell preservation solution Easyfix].
AB  - The aim of this study is to validate the liquid cell preservation solution
      Easyfix for DNA detection of the HPV oncogene using the Hybrid Capture II method.
      256 specimens were selected for the cytological study, possible biopsy and HPV
      oncogene search with the Easyfix fixative fluid and the Cervical Sampler
      transport medium. The results obtained with both mediums are comparable
      regardless of the cytological type. The relevance of a cytological study combined
      with the HPV search is stressed. To conclude, it is possible to put forward that
      the liquid cell preservation solution Easyfix can be used to detect the HPV
      oncogene using the Hybrid Capture II method.

PMID- 15563428
TI  - [Evaluation of an automated method for measuring low-density lipoprotein
      cholesterol].
AB  - We evaluated an automated method for measuring low-density lipoprotein
      cholesterol (LDL-cholesterol) with Integra 800 (Roche Diagnostics). This method
      uses detergents which show selectivity for the different lipoproteins. Our
      evaluation has shown a within run imprecision of 2% and a between-assay
      imprecision of 1.2%. This method was not perturbed by haemoglobin, bilirubin or
      lipids. However, the reagents remain expensive: we will use it when calculation
      or interpretation of lipid results are not possible.

PMID- 15563429
TI  - [Urinary iodide analysis: critical study of the digestion method].
AB  - Urinary iodine is largely measured in microtiter plates by a colorimetic ceric
      arsenic assay based on the Sandell-Kolthoff reaction. However, a preliminary
      digestion step is necessary and requires a particular care not only to transform
      all the iodo-compounds into iodide but also to prevent the formation of
      substances liable to the disturb of the subsequent redox reaction. In the present
      study we tested three types of digestion processes, among them two conventional
      methods (ammonium persulfate and chloric acid) and a new one using combined
      nitric acid/hydrochloric acid. Results showed that important errors may be
      obtained with the chloric acid and the ammonium persulfate digestions. These
      discordances were the consequence of either an incomplete transformation of iodo
      compounds or an oxidation of iodide into molecular iodine or a colorimetric assay
      disturbance due to a residual yellow coloring. No problems were evidenced with
      the combined nitric acid/hydrochloric acid process, which remains the better
      alternative to evaluate the urinary iodine. It could also provide a particularly
      useful means of assessing the iodine status in epidemiological studies.

PMID- 15563430
TI  - [Interference of hemolysis on haptoglobin determined by kinetic
      immunonephelometry and comparison between phenotypes].
AB  - The aim of the study was to check if a slight and non visible hemolysis to naked
      eye such as that induced by blood coagulation could interfere in the
      immunonephelometric measurement of haptoglobin, and if this interference was
      dependent on the protein phenotype. Results confirmed that blood coagulation
      induced a non visible hemolysis whose intensity markedly varied from one specimen
      to another. Under our conditions (kinetic measurement with a Beckman Coulter
      immunonephelometer), we observed with the sera a negative interference linked to
      the hemolysis induced by blood coagulation when compared to corresponding plasmas
      obtained with lithium heparinate (p < 0,005). It was checked also that this
      anticoagulant did not induce a positive interference. Hemolysis interference was
      not found phenotype dependent. These results lead us to recommend to perform
      haptoglobin measurements on heparinised plasmas.

PMID- 15563431
TI  - [Evaluation of lipoperoxidation in hemodialysis patients with a simple test using
      the "Free Oxygen Radical Monitor"].
AB  - Incidence of cardiovascular events is higher in hemodialysis (HD) patients than
      in general population. Oxidative stress represents a major specific risk factor
      of accelerated atheroma particularly in association with inflammation and
      malnutrition. The aim of our study is to evaluate a simple test of lipid
      peroxidation measurement using the "Free Oxygen Radical Monitor" (FORM)
      (Callegari, Italy). The results obtained in HD patients were compared to standard
      oxidative stress markers, such as thiobarbituric acid reacting substances,
      carbonyls and vitamin E in plasma, and glutathione, oxidized to reduced form
      ratio, in erythrocytes. In conclusion, the FORM system presents no sufficient
      sensibility and specificity to determine oxidative stress in HD patients.

PMID- 15563432
TI  - [Redox status in HIV+ patients under HAART].
AB  - Oxidative stress decreases immune defences and is also suggested to participate
      in the activation of HIV virus replication. That is why we decided to explore
      some biomarkers of oxidative stress (reduced glutathione, lipoperoxides, true
      malondialdehyde and vitamin C) in 20 HIV positive patients whose HIV replication
      was determined by measurement of RNA viral load. Reduced glutathione is decreased
      in HIV positive patients, without correlation with the viral load. The patients
      mean content of lipoperoxides is twice that of controls but with such a large
      range that there is no statistical difference.

PMID- 15563433
TI  - [Influence of pyridoxal phosphate in measuring aminotransferases activities in
      patients with viral hepatitis].
AB  - Effect of a pyridoxal phosphate (PP) supplementation of reagents used for ALT and
      AST measurement was studied in serum of 20 patients suffering from viral
      hepatitis. Measurements of enzyme activities were carried out at 37 degrees C,
      using an automate (AU 600, Olympus). Significant differences (p < 0.0001) were
      observed both for ALT and AST, meanwhile they were more marked for ALT than for
      AST. This difference was associated with a strong interindividual variability
      regarding PP activation effect on ALT. In conclusion, aminotransferase
      measurements should be carried out with a reagent supplemented with PP, when the
      enzyme activity is used to evaluate a cytolysis. The same recommendation applies
      when ALT results are integrated into various combinations developed for the
      evaluation of liver status.

PMID- 15563434
TI  - Can a food frequency questionnaire be used to capture dietary intake data in a 4
      week clinical intervention trial?
AB  - Collecting dietary data in the clinical research setting is labour intensive and
      can be burdensome for study participants. The aim of this study was to assess the
      agreement between data obtained from 2 different dietary assessment methods, a 74
      item semi-quantitative food frequency questionnaire (FFQ) and 3-day weighed food
      records (WFR) used to estimate dietary intake over the preceding month. One
      hundred and fifty nine subjects, aged between 31 and 74 years (53 males, 65
      females), enrolled in a clinical trial at the Commonwealth Scientific and
      Industrial Research Organisation, Division of Health Sciences and Nutrition,
      (CSIRO HSN) Adelaide, Australia. Group mean intakes and individual mean intakes
      estimated by the two measures were compared. One hundred and eighteen (91%) three
      day WFR and their corresponding FFQ were analysed. Pearson correlation
      coefficients ranged from 0.22 for cholesterol to 0.78 for alcohol (median 0.41).
      Mean energy and nutrient intakes were within +/- 20% difference. The FFQ gave
      lower carbohydrate intake estimates, percentage energy from carbohydrate (P
      <0.001) and dietary fibre (P <0.05) and gave higher percentage energy from
      saturated fat estimates, poly-unsaturated fatty acids (P <0.001) and mono
      unsaturated fatty acids (P <0.05). Subjects were also ranked into quintiles and
      the quintiles cross-tabulated. The FFQ classified more than two thirds of the
      subjects within +/-1 quintile difference for all nutrients. We conclude that this
      FFQ can capture similar information as WFR and may be used for estimation of
      dietary intakes over a relatively short time in clinical intervention trials.

PMID- 15563435
TI  - Body mass status of school children and adolescents in Kuala Lumpur, Malaysia.
AB  - Lifestyle and disease patterns in Malaysia have changed following rapid economic
      development. It is important to find out how these changes have affected the
      nutritional status and health behaviour of the population, especially school
      children and adolescents. Therefore a survey on school children's and
      adolescents' health behaviours and perception in Kuala Lumpur was initiated. This
      paper only reports the observed body mass status of the school children. A total
      of 3620 school children were selected in this survey using the method of multi
      stage sampling. The students were surveyed using pre-tested questionnaires while
      weight and height were measured by the research team in the field. Using the cut
      off of BMI-for-age >or= 95th percentile and <5th percentile for overweight and
      underweight respectively, there were a total of 7.3% of overweight students and
      14.8% of underweight students. When analysed by gender; 7.5% of boys and 7.1%
      girls were overweight, while 16.2% of the boys and 13.3% of the girls were
      underweight. The youngest age group (11 years old) had the highest prevalence of
      underweight as well as overweight. With increasing age, the prevalence of
      underweight and overweight decreased and more children were in the normal weight
      range. The overall prevalence of overweight among the three ethnic groups was
      similar. However the prevalence of underweight was highest among the Indian
      students (24.9%), followed by Malays (18.9%) and Chinese (9.5%) (P <0.001). The
      results showed that both the problems of under- and over-nutrition co-exist in
      the capital city of Malaysia. The promotion of healthy eating and physical
      activities is required to address the problems of under- and over-nutrition in
      order to build up a strong and healthy nation in the future.

PMID- 15563436
TI  - Haematocrit levels and anaemia in Australian children aged 1-4 years.
AB  - The aim of this study was to describe the prevalence of anaemia, mean haematocrit
      levels, and the risk factors influencing haematocrit in participants of the 1995
      National Survey of Lead in Children. A nationally-representative cross-sectional
      survey of children aged 1-4 years inclusive was done. Mean haematocrit and the
      proportion with anaemia using both the US and WHO haematocrit-based criteria were
      calculated. Multivariate regression was used to identify factors associated with
      haematocrit. Mean haematocrit level was 38.8% (95% CI: 38.6 - 39.1%) and varied
      with age of child, state/territory of residence and whether the child was taking
      supplements. It did not vary by sex, Aboriginal identification, maternal
      birthplace, whether the child ate meat or any other selected characteristic. The
      factors identified explained only 4% of the variation in haematocrit levels. The
      prevalence of anaemia was 3.3% (95% CI: 2.4 - 4.5%) based on the US criteria and
      2.0% (95% CI: 1.3 - 3.1%) based on the WHO criteria. The prevalence of anaemia in
      this national survey was lower than the prevalence of iron deficiency anaemia
      reported in several more localised studies.

PMID- 15563437
TI  - Carotenoid status among preschool children with vitamin A deficiency in the
      Republic of the Marshall Islands.
AB  - Although carotenoids are known to be important dietary sources of vitamin A,
      there have been few epidemiological studies that have characterized the serum
      concentrations of major dietary carotenoids among preschool children with vitamin
      A deficiency. We conducted a population-based, cross-sectional study of serum pro
      vitamin A carotenoids (alpha -carotene, beta-carotene, beta-cryptoxanthin), non
      provitamin A carotenoids (lutein/zeaxanthin, and lycopene), and retinol among 278
      children, aged 1-5 y, in the Republic of the Marshall Islands. Vitamin A
      deficiency was defined as serum retinol <0.70 micromol/L. Geometric mean serum
      concentrations of carotenoids among children with and without vitamin A
      deficiency were 0.003 vs 0.006 micromol/L for alpha-carotene (P = 0.0017), 0.011
      vs 0.023 micromol/L for beta-carotene (P <0.0001), 0.023 vs 0.034 micromol/L for
      beta-cryptoxanthin (P = 0.0075), 0.007 vs 0.012 micromol/L for lycopene (P =
      0.037), 0.044 vs 0.052 micromol/L for lutein/zeaxanthin (P = 0.2), and 0.045 vs
      0.074 micromol/L for total provitamin A carotenoids (P <0.0001) respectively. In
      a multivariate analysis adjusting for sex, age (Odds Ratio [O.R.] 1.44, 95%
      confidence interval [C.I.] 1.16-1.78), and serum provitamin A carotenoids (O.R.
      0.49, 95% C.I. 0.34-0.71) were associated with vitamin A deficiency, but serum
      non-provitamin A carotenoids were not associated with vitamin A deficiency (O.R.
      0.93, 95% C.I. 0.67-1.28). Preschool children with vitamin A deficiency in the
      Republic of the Marshall Islands have extremely low serum concentrations of
      provitamin A carotenoids and interventions are needed to improve the dietary
      intake of provitamin A carotenoids among Marshallese children.

PMID- 15563438
TI  - The effects of a high calcium dairy food on bone health in pre-pubertal children
      in New Zealand.
AB  - Childhood and adolescence is the period of most rapid skeletal growth in an
      individual's lifetime. A greater peak bone mass achieved in the first 2-3 decades
      of life, may protect against the risk of osteoporotic fracture in later life. The
      aim of this randomized, controlled study was to assess in pre-pubertal boys and
      girls (aged 8-10 years) the effect of 18 months of a calcium enriched, cocoa
      flavoured product on bone density, bone growth and bone size in New Zealand
      children. One hundred and fifty four pre-pubertal boys and girls (aged 8-10
      years) were randomized to receive a high calcium dairy drink or a control drink
      reconstituted with water for 18 months. They were assessed at baseline and then
      every 6 months for the first 18 months, while they were having the supplement;
      they were then followed up 12 months after supplementation had finished. Bone
      mineral density and bone mineral content were assessed at the total body, hip and
      spine. Indicators of bone size (vertebral width and height) were also measured at
      the spine. Anthropometric data was collected, medical history questionnaires were
      administered (including the Tanner or pubertal stage questionnaire), dietary
      calcium intake was assessed with a calcium food frequency questionnaire and
      calcium supplement compliance was determined. There was no significant difference
      between the 2 groups for bone mineral density or bone mineral content at any time
      point. There was no difference in vertebral height or width at any stage of the
      study, indicating no additional influence on bone size at the lumbar vertebrae.
      There were no significant differences between height, weight, lean mass or fat
      mass at any time point. Both groups had higher habitual calcium intakes than
      recommended for this age group going into the study and throughout the study. In
      this 2(1/2) year study (18 months supplementation, 1 year follow-up) we did not
      observe a difference in bone mineral density in pre-pubertal children. This was
      probably due to their high habitual dietary calcium intake whereby minimal
      addition of calcium to the diet reached the threshold level where no further
      benefit was seen. There were no significant differences between the two groups in
      body composition. Growth and the mean height and weight remained between the 50th
      and 75th percentile for their age. We have shown calcium supplementation in
      children with high habitual dietary calcium intake appears not to have additional
      effects on bone mass. Calcium supplementation needs to be targeted in those
      children with low habitual dietary calcium intake.

PMID- 15563439
TI  - Comparison of serum levels of iron, zinc and copper in anaemic and non-anaemic
      pregnant women in China.
AB  - Zinc and copper deficiency is associated with anaemia or iron deficiency and
      affects fetus growth and pregnant women during pregnancy. To examine iron, zinc
      and copper status of Chinese pregnant women with and without anaemia in the third
      trimester, 1185 subjects were enrolled for measurements of Hb, ferritin,
      transferrin, soluble transferrin receptor (sTfR), and serum iron, zinc and
      copper. The results showed that there were lower levels of ferritin (14.1
      microg/L) and transferrin (3.33 g/L) in subjects with Hb<or=100g/L as compared
      with subjects with Hb>or=101 g/L. sTfR levels in subjects with Hb<or=100g/L were
      significantly higher than those in subjects with Hb>or=120 g/L (38.5 nmol/L vs.
      25.04 nmol/L, P<0.001). Serum iron was lower in subjects with Hb<or=100 g/L than
      those with Hb>or=120 g/L (871 microg/L vs. 990 microg/L, P<0.01). Lower levels of
      serum iron and zinc were also found in anaemic (Hb<110 g/L) as compared with non
      anaemic women (Hb>or=110 g/L). Frequencies of marginal deficiencies in serum iron
      and zinc were 41.58% and 51.05% respectively higher in anaemic than in non
      anaemic subjects. Distribution of serum zinc and iron showed a decreasing trend
      as Hb decreased. Few anaemic as well as non-anaemic subjects had copper
      deficiency although copper and Hb levels were found inversely correlated and the
      ratio of copper/iron was higher in anaemic than in non-anaemic group. In
      conclusion, a lower level of serum zinc in anaemic pregnant women might be
      related to anaemia and iron deficiency during pregnancy. Therefore, combined zinc
      and iron supplementation should be recommended to Chinese pregnant women,
      especially those with anaemia.

PMID- 15563440
TI  - Effects of 4 weeks iron supplementation on haematological and immunological
      status in elite female soccer players.
AB  - The effects of 4 weeks iron supplementation on haematological and immunological
      status were studied in 25 elite female soccer players aged 20-28 years. The
      subjects were randomized and assigned to one of the following two groups;
      subjects given 40 mg/day iron supplementation (S group) or those given placebo (C
      group). The oral iron supplementation (40 mg elemental iron) was taken in 15 ml
      solution once a day by the S group, and the C group took a placebo for 4 weeks.
      Daily energy and protein intakes met the Korean Recommended Dietary Allowances.
      Blood haemoglobin concentration did not change in the S group, but decreased
      significantly (P<0.05) in the C group over the 4-week experimental period.
      Haematocrit, mean cell volume, mean cell haemoglobin and total iron binding
      capacity decreased significantly, and mean cell haemoglobin concentration
      increased significantly (P<0.05) in both the S and C groups. Plasma ferritin
      concentration increased significantly (P<0.05) in the S group, but did not change
      in the C group. The change of plasma immunological parameters and erythrocyte
      anti-oxidative enzyme activities were almost the same between the S and C groups.
      These results suggest that 4 weeks of iron supplementation by elite female soccer
      players significantly increased body iron stores and inhibited decrease of
      haemoglobin concentration induced by soccer training.

PMID- 15563441
TI  - High prevalence of low dietary calcium and low vitamin D status in healthy south
      Indians.
AB  - Calcium and vitamin D under nutrition can adversely affect the bone mineral
      metabolism. There is no population-based study from India documenting dietary
      habits, serum calcium and vitamin D levels. Our study investigated the dietary
      habits of rural and urban societies in and around Tirupati and their relationship
      with serum calcium, phosphorous and vitamin D [25(OH)D] levels. Four hundred and
      seven subjects from 5 villages around Tirupati, (rural population) and 125
      asymptomatic staff of our hospital (urban population) were studied. Dietary
      intakes of calcium, phosphorous and phytates were documented by diet history.
      Serum calcium, phosphorus and 25 (OH) D levels were estimated in 191 rural
      subjects and 125 urban subjects. Compared to urban subjects, rural subjects had a
      significantly lower intake of dietary calcium (P <0.0001) and a significantly
      higher dietary phytate/calcium ratio and serum calcium and 25 (OH) D levels (P
      <0.0001). Dietary calcium intake was inadequate in both rural and urban subjects
      compared to the recommended daily allowances (RDA) for our country. About 31% of
      the population had normal vitamin D levels, 54% had vitamin D insufficiency and
      15% vitamin D deficiency. About two-thirds of the population had low levels of
      vitamin D. Inadequate dietary calcium intake associated with high phytate/calcium
      ratio reduces the bioavailable calcium in the gut. Hence, there is a need to
      fortify food with calcium and to propose new guidelines for 25 (OH) D in Indian
      subjects. Multicentric studies with large sample populations are required to
      generate normal standards and nationally relevant guidelines.

PMID- 15563442
TI  - Health characteristics of older Australian dietary supplement users compared to
      non-supplement users.
AB  - The aim of this study was to measure the prevalence of dietary and health
      supplement use among Australians aged 65 years and over, and to contrast the
      health differences between supplement users and non-supplement users. Data was
      obtained from 1,263 randomly selected older Australians, who provided general
      demographic data, in addition to information related to their health, symptoms
      experienced and uses of medication, including dietary supplements. Supplement use
      was reported by 43% of the sample (52% of females and 35% of males). This
      investigation has revealed distinct differences in the health profile of older
      supplement users compared to non-users. Although there was no difference in the
      number of visits to medical doctors or self-rated health status between
      supplement users and non-supplement users, supplement users were more likely to
      report arthritis and osteoporosis, and experience more symptoms and consume more
      medication than non-supplement users. In contrast, there was a reduced likelihood
      of taking a supplement for those with hypertension and by those using blood
      pressure medication and heart tablets. These results suggest that older dietary
      supplement users may benefit from education and professional advice to assist
      them make appropriate and informed choices, particularly if they expect these
      preparations to attenuate their health concerns.

PMID- 15563443
TI  - Nutritional status of Saudi males living in the Riyadh nursing home.
AB  - This study evaluated the nutritional status of residents in the Riyadh nursing
      home, using anthropometric and haematological measurements. All male residents
      (N=84; age range 24-80 years) in the Riyadh nursing home were included in the
      study. Weight, height, body mass index, triceps skin fold thickness, and mid-arm
      muscle circumference were measured. Furthermore, serum concentrations of albumin,
      haemoglobin and haematocrit were measured. About 13% of adult residents and 11%
      of elderly residents were considered to be underweight (body mass index <18.5
      kg/m(2)). From estimations of fat mass in the periphery, using triceps skin fold
      thickness, it appears that the elderly residents had significantly lower fat mass
      compared to the adult residents (P <0.05). The results showed that more than 40%
      of residents had low mid-arm muscle circumference (<22.3 cm). Serum albumin
      concentration was significantly lower in the elderly group than in the adult
      group (P<0.01). No significant difference was found in haematocrit level between
      the adult and elderly residents. Within the adult group, about 38% of residents
      had low haemoglobin level (<12 mg/dl), and this proportion was even higher, about
      55%, in elderly residents. Based on body mass index or albumin to determine the
      prevalence of malnutrition among residents, the results have shown that the
      prevalence of undernourished residents was not higher than the prevalence of
      undernourished nursing-home residents reported in other studies. The percentage
      of elderly residents with anaemia was appreciable. Thus, undernourished and
      anemic residents should have special dietary and medical attention. Early
      detection of malnutrition upon admission would lead to early intervention and
      thus to reduced complications and medical-treatment costs. Staff working in
      nursing homes should be aware of the nutritional guidelines for health and
      disease.

PMID- 15563444
TI  - Dietary intake and the risk of coronary heart disease among the coconut-consuming
      Minangkabau in West Sumatra, Indonesia.
AB  - Several nutrition and non-nutritional pathways are recognised in the development
      and occurrence of cardiovascular disease. In many populations, high intakes of
      saturated fat are associated with elevated serum cholesterol concentrations and
      increased coronary heart disease (CHD) mortality. However, several studies report
      that hyperlipidaemia and heart diseases are not common among populations who
      consume coconut, a source of saturated fat. A case-control study was conducted
      among the Minangkabau known to be high coconut consumers to examine the
      difference in food patterns and risk of coronary heart disease (CHD) between the
      coronary cases and their gender- and age-matched apparently healthy counterparts
      serving as controls. Eligible subjects with CHD were identified through the co
      operation of five participating hospitals located in Padang and Bukittinggi in
      West Sumatra, Indonesia. A total of 93 eligible cases (62 men and 31 women) in
      the Case group and 189 subjects (113 men and 76 women) in the Control group were
      recruited. Information on the intakes of individual foods and dishes over the
      preceding 12 months was obtained using a semi-quantitative food frequency
      questionnaire. The Case groups had significantly higher intakes of meats, eggs,
      sugar, tea, coffee and fruits, but lower intakes of soy products, rice and
      cereals compared to the controls. Coconut consumption as flesh or milk was not
      different between cases and controls. The cases had significantly higher intakes
      of protein and cholesterol, but lower intake of carbohydrate. Similar intakes of
      saturated and unsaturated fatty acids between the cases and controls indicated
      that the consumption of total fat or saturated fat, including that from coconut,
      was not a predictor for CHD in this food culture. However, the intakes of animal
      foods, total protein, dietary cholesterol and less plant derived carbohydrates
      were predictors of CHD.

PMID- 15563445
TI  - Nutritional analysis of blenderized enteral diets in the Philippines.
AB  - The objective of this study was to analyze the nutritional quality and viscosity
      of blenderized enteral tube feedings (BTFs) from four hospitals in the
      Philippines. Samples of two different BTFs (one standard and one modified) were
      collected from each hospital on three separate occasions and analyzed for
      macronutrients, micronutrients, and viscosity. There was considerable variation
      among the BTFs for the concentrations of most nutrients measured. For standard
      BTF samples, the caloric density ranged from 66-123 kcal/100g and the percentages
      of total weight for protein, carbohydrate, and fat ranged from 1.5-4.0%, 8.6
      21.4%, and 0.27-3.40%, respectively. Levels of specific vitamins were
      undetectable in 10 standard and 15 modified BTF samples. In samples where vitamin
      levels were detectable, results were: vitamin A, 625-8850 IU/kg; riboflavin, 0.40
      5.00 mg/kg; and pyridoxine, 0.14-3.00 mg/kg. Mineral concentrations also varied
      greatly (eg calcium, 64-524 mg/kg; sodium, 148-886 mg/kg; iron, 3.0-13.7 mg/kg;
      and zinc, 1.8- 11.5 mg/kg). Correlation coefficients were statistically
      significant only for carbohydrate (r = 0.48, P = 0.017). Measured values tended
      to be lower than expected values for all nutrients, although the difference was
      statistically significant only for calories (P = 0.023). The viscosity of BTF
      samples ranged from 2.3-45,060 centipoise, excluding three samples that were too
      viscous for analysis. This study demonstrates that hospital prepared blenderized
      enteral tube feedings render unpredictable levels of micronutrients and
      macronutrients and appear likely to deliver less than the desired amounts of
      nutrients. Additionally, the viscosity of these feedings may be unsuitable for
      infusion through feeding tubes.

PMID- 15563446
TI  - Lipid peroxidation and antioxidants status in patients with papillary thyroid
      carcinoma in India.
AB  - The levels of lipid peroxidation products (TBARS), non-enzymatic antioxidants and
      enzymatic antioxidants activity were investigated in plasma and erythrocytes of
      twenty clinically diagnosed stage II papillary thyroid cancer patients and an
      equal number of age and sex matched healthy subjects. An increase in the levels
      of lipid peroxidation products, decrease in non-enzymatic antioxidants levels and
      enzymatic antioxidant activities in plasma and erythrocytes were detected in
      papillary thyroid cancer patients as compared to healthy subjects. Impairment in
      antioxidant defence mechanisms are responsible for enhanced lipid peroxidation
      observed in plasma and erythrocytes of papillary thyroid cancer patients.

PMID- 15563447
TI  - Potential anticancer effect of red spinach (Amaranthus gangeticus) extract.
AB  - The objective of this study was to determine the anti cancer effects of red
      spinach (Amaranthus gangeticus Linn) in vitro and in vivo. For in vitro study,
      microtitration cytotoxic assay was done using 3-(4,5-dimethylthiazol-2-il)-2,5
      diphenil tetrazolium bromide (MTT) kit assay. Results showed that aqueous extract
      of A gangeticus inhibited the proliferation of liver cancer cell line (HepG2) and
      breast cancer cell line (MCF-7). The IC(50) values were 93.8 mu g/ml and 98.8 mu
      g/ml for HepG2 and MCF-7, respectively. The inhibitory effect was also observed
      in colon cancer cell line (Caco-2), but a lower percentage compared to HepG2 and
      MCF-7. For normal cell line (Chang Liver), there was no inhibitory effect. In the
      in vivo study, hepatocarcinogenesis was monitored in rats according to Solt and
      Farber (1976) without partial hepatectomy. Assay of tumour marker enzymes such as
      glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), uridyl
      diphosphoglucuronyl transferase (UDPGT) and alkaline phosphatase (ALP) were
      carried out to determine the severity of hepatocarcinogenesis. The result found
      that supplementation of 5%, 7.5% and 10% of A. gangeticus aqueous extract to
      normal rats did not show any significant difference towards normal control (P
      <0.05). The exposure of the rats to chemical carcinogens diethylnitrosamine (DEN)
      and 2-acetylaminofluorene (AAF) showed a significant increase in specific enzyme
      activity of GGT, GST, UDPGT and ALP compared to normal control (P <0.05).
      However, it was found that the supplementation of A. gangeticus aqueous extract
      in 5%, 7.5% and 10% to cancer-induced rats could inhibit the activity of all
      tumour marker enzymes especially at 10% (P <0.05). Supplementation of anti cancer
      drug glycyrrhizin at suggested dose (0.005%) did not show any suppressive effect
      towards cancer control (P <0.05). In conclusion, A. gangeticus showed anticancer
      potential in in vitro and in vivo studies.

PMID- 15563448
TI  - Inhibitory effect of clonal oregano extracts against porcine pancreatic amylase
      in vitro.
AB  - Oregano (Origanum vulgare) is a rich source of natural phenolic antioxidants and
      has potential to be a source of nutritional ingredients for functional foods.
      Herbs such as oregano have long been used in food preservation and in traditional
      medicine in the treatment of common ailments and have potential for positive
      modulation of oxidation-linked diseases such as diabetes. One of the potentially
      important components of anti-diabetic activity by oregano extract is mild amylase
      inhibition by phenolic antioxidants to help contribute towards management of
      hyperglycemia. Previously, we reported the ability of rosmarinic acid, one of the
      principal phenolic components of oregano, to inhibit porcine pancreatic amylase
      (PPA) activity. Here, we investigated the effect of 50% ethanol extracts of
      eleven phenolic antioxidant-rich oregano clonal lines on the activity of PPA in
      vitro. To this end, we analyzed extract total soluble phenolic content by the
      Folin-Ciocalteu reagent method, rosmarinic acid (RA), protochatechuic acid (PA),
      quercetin, and p-coumaric acid (pCA) contents by HPLC, antioxidant activity as
      1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging, and PPA-inhibitory
      activity by incubation of the enzyme with clonal oregano extracts and
      characterization of the activity of the phenolic-bound enzyme. Clonal oregano
      extracts inhibited the activity of PPA in vitro by 9-57%. Amylase inhibition by
      oregano extract was associated with extract total phenolic content and RA,
      quercetin, PA, and pCA content, as well as extract antioxidant activity and
      protein content. Our finding that clonal oregano extracts can inhibit PPA
      supports a potential new functionality for oregano as an anti-hyperglycemic
      agent. This provides an opportunity for a food-based strategy for modulation of
      starch breakdown to glucose, which could contribute to the management of
      hyperglycemia and diabetes complications in the long term.

PMID- 15563449
TI  - Up-regulation of the endocannabinoid system in the uterus of leptin knockout
      (ob/ob) mice and implications for fertility.
AB  - The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG)
      are under the negative control of leptin in the rodent hypothalamus. As leptin
      and endocannabinoids play opposite roles in the control of reproduction, we have
      investigated whether the impaired fertility typical of leptin-defective ob/ob
      mice is due, in part, to enhanced uterine endocannabinoid levels. We found that
      levels of both anandamide and 2-AG in the uterus of ob/ob mice are significantly
      elevated with respect to wild-type littermates, due to reduced hydrolase activity
      in the case of anandamide, and to reduced monoacylglycerol lipase and enhanced
      diacylglycerol lipase activity in the case of 2-AG. Furthermore, the process
      mediating endocannabinoid cellular uptake was also impaired in ob/ob mice,
      whereas the levels of cannabinoid and anandamide receptors were not modified.
      Although ineffective in wild-type mice, treatment of ob/ob mice with leptin re
      established endocannabinoid levels and enzyme activities back to the values
      observed in wild-type littermates. Finally, treatment of ob/ob females with the
      CB1 receptor antagonist SR141716A did not improve their fertility, and inhibition
      of endocannabinoid inactivation with the endocannabinoid uptake inhibitor OMDM-1
      in wild-type females did not result in impaired fertility.

PMID- 15563450
TI  - The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an
      ileal basolateral bile acid transporter.
AB  - Bile acids are transported across the ileal enterocyte brush border membrane by
      the well characterized apical sodium-dependent bile acid transporter (Asbt)
      Slc10a2; however, the carrier(s) responsible for transporting bile acids across
      the ileocyte basolateral membrane into the portal circulation have not been fully
      identified. Transcriptional profiling of wild type and Slc10a2 null mice was
      employed to identify a new candidate basolateral bile acid carrier, the
      heteromeric organic solute transporter (Ost)alpha-Ostbeta. By Northern blot
      analysis, Ostalpha and Ostbeta mRNA was detected only in mouse kidney and
      intestine, mirroring the horizontal gradient of expression of Asbt in the
      gastrointestinal tract. Analysis of Ostalpha and Ostbeta protein expression by
      immunohistochemistry localized both subunits to the basolateral surface of the
      mouse ileal enterocyte. The transport properties of Ostalpha-Ostbeta were
      analyzed in stably transfected Madin-Darby canine kidney cells. Co-expression of
      mouse Ostalpha-Ostbeta, but not the individual subunits, stimulated Na(+)
      independent bile acid uptake and the apical-to-basolateral transport of
      taurocholate. In contrast, basolateral-to-apical transport was not affected by
      Ostalpha-Ostbeta expression. Co-expression of Ostalpha and Ostbeta was required
      to convert the Ostalpha subunit to a mature glycosylated endoglycosidase H
      resistant form, suggesting that co-expression facilitates the trafficking of
      Ostalpha through the Golgi apparatus. Immunolocalization studies showed that co
      expression was necessary for plasma membrane expression of both Ostalpha and
      Ostbeta. These results demonstrate that the mouse Ostalpha-Ostbeta heteromeric
      transporter is a basolateral bile acid carrier and may be responsible for bile
      acid efflux in ileum and other ASBT-expressing tissues.

PMID- 15563451
TI  - Nucleo-cytoplasmic shuttling of Id2, a negative regulator of basic helix-loop
      helix transcription factors.
AB  - Id proteins function as negative regulators for basic helix-loop-helix
      transcriptional factors that play important roles in cell fate determination.
      They preferentially associate with ubiquitously expressed E proteins of the basic
      helix-loop-helix family and prevent them from binding to DNA and activating
      transcription. Although their small size suggests that Id proteins enter and exit
      the nucleus by passive diffusion, several studies have indicated that other
      pathways may regulate their subcellular localization. In this study, we obtained
      evidence that Id2 has the ability to shuttle between the nucleus and the
      cytoplasm. When passive diffusion was prevented by fusion with green fluorescent
      protein (GFP), Id2 was predominantly localized in the cytoplasm. Using GFP fusion
      constructs, we demonstrated that the C-terminal region is required for
      cytoplasmic localization. Nuclear accumulation of GFP-Id2 in cells treated with
      the nuclear export inhibitor leptomycin B suggests that the nuclear export
      receptor chromosome region maintenance protein 1 mediates the cytoplasmic
      localization of Id2. Id2 contains two putative leucine-rich nuclear export
      signals, and the nuclear export signal in the C-terminal region is essential for
      nuclear export. On the other hand, the helix-loop-helix domain is important for
      nuclear localization. Finally, experiments using reporter assays revealed an
      inverse correlation between nuclear export and transcriptional repression via the
      E-box sequence. Based on all these findings, we propose that nucleo-cytoplasmic
      shuttling is a novel mechanism for the regulation of Id2 function.

PMID- 15563452
TI  - DRO1, a gene down-regulated by oncogenes, mediates growth inhibition in colon and
      pancreatic cancer cells.
AB  - Neoplastic progression in human tissues appears to be paralleled by a series of
      genetic and epigenetic alterations. In human colorectal cancers, defect Wnt/beta
      catenin/T-cell factor and RAS/RAF signaling pathways have a major contributing
      role in tumor initiation and progression. To date, much of the research on the
      consequences of beta-catenin activation has been focused on genes whose
      expression is believed to be activated by beta-catenin-associated T-cell factor
      dependent transcription. Little is known about genes whose expression may be down
      regulated secondary to beta-catenin activation. Using a subtractive suppression
      hybridization approach, we identified a gene with markedly decreased expression
      in rat RK3E epithelial cells neoplastically transformed by beta-catenin. Because
      expression of this gene was also down-regulated in RK3E transformed by several
      other oncogenes, the gene was named DRO1 for "down-regulated by oncogenes 1."
      Compared with corresponding normal tissues, DRO1 expression was found to be very
      reduced in colon and pancreatic cancer cell lines as well as in most colorectal
      cancer specimens. The predicted DRO1 protein contains three repetitive elements
      with significant similarity to the carboxyl-terminal regions of the predicted
      proteins from DRS/SRPX/ETX1 and SRPUL genes, suggesting the existence of a new
      protein family. Ectopic expression of DRO1 in neoplastically transformed RK3E or
      colorectal and pancreatic cancer cell lines lacking endogenous DRO1 expression
      resulted in substantial inhibition of growth properties. DRO1 was found to
      suppress anchorage independent growth and to sensitize cells to anoikis and CD95
      induced apoptosis. Our findings suggest that inhibition of DRO1 expression may be
      an important event in the development of colorectal and pancreatic cancers.

PMID- 15563453
TI  - Nuclear hormone receptor coregulator GRIP1 suppresses, whereas SRC1A and p/CIP
      coactivate, by domain-specific binding of MyoD.
AB  - p160 coregulators were initially identified as nuclear hormone receptor
      coactivators. In this study, functional data demonstrate that members of the
      three p160 families can have opposing roles in regulating gene expression by the
      same transcription factor. Both SRC1A and p/CIP function as coactivators for MyoD
      mediated transcription whereas GRIP1 acts negatively as a (co)repressor. SRC1A
      and p/CIP predominantly interact with distinct sites on the NH2-terminal
      activation domain of MyoD. GRIP1 binds to both these regions but it alone, and
      neither SRC1A nor p/CIP, also interacts with specific sites on MyoD that are
      critical for the binding of the essential MyoD coactivator, p300. This suggests
      that competition by GRIP1 for SRC1A, p/CIP, and p300 binding sites on a
      transcription factor may regulate the activity of the factor.

PMID- 15563454
TI  - Identification of an invasion regulatory domain within the core protein of
      syndecan-1.
AB  - Among the four members of the syndecan family there exists a high level of
      divergence in the ectodomain core protein sequence. This has led to speculation
      that these core proteins bear important functional domains. However, there is
      little information regarding these functions, and thus far, the biological
      activity of syndecans has been attributed largely to their heparan sulfate
      chains. We have previously demonstrated that cell surface syndecan-1 inhibits
      invasion of tumor cells into three-dimensional gels composed of type I collagen.
      Inhibition of invasion is dependent on the syndecan heparan sulfate chains, but a
      role for the syndecan-1 ectodomain core protein was also indicated. To more
      closely examine this possibility and to map the regions of the ectodomain
      essential for syndecan-1-mediated inhibition of invasion, a panel of syndecan-1
      mutational constructs was generated, and each construct was transfected
      individually into myeloma tumor cells. The anti-invasive effect of syndecan-1 is
      dramatically reduced by deletion of an ectodomain region close to the plasma
      membrane. Further mutational analysis identified a stretch of 5 hydrophobic amino
      acids, AVAAV (amino acids 222-226), critical for syndecan-1-mediated inhibition
      of cell invasion. This invasion regulatory domain is 26 amino acids from the
      start of the transmembrane domain. Importantly, this domain is functionally
      specific because its mutation does not affect syndecan-1-mediated cell binding to
      collagen, syndecan-1-mediated cell spreading, or targeting of syndecan-1 to
      specific cell surface domains. This invasion regulatory domain may play an
      important role in inhibiting tumor cell invasion, thus explaining the observed
      loss of syndecan-1 in some highly invasive cancers.

PMID- 15563455
TI  - The Mu transposase interwraps distant DNA sites within a functional transpososome
      in the absence of DNA supercoiling.
AB  - A Mu transpososome assembled on negatively supercoiled DNA traps five supercoils
      by intertwining the left (L) and right (R) ends of Mu with an enhancer element
      (E). To investigate the contribution of DNA supercoiling to this elaborate
      synapse in which E and L cross once, E and R twice, and L and R twice, we have
      analyzed DNA crossings in a transpososome assembled on nicked substrates under
      conditions that bypass the supercoiling requirement for transposition. We find
      that the transposase MuA can recreate an essentially similar topology on nicked
      substrates, interwrapping both E-R and L-R twice but being unable to generate the
      single E-L crossing. In addition, we deduce that the functional MuA tetramer must
      contribute to three of the four observed crossings and, thus, to restraining the
      enhancer within the complex. We discuss the contribution of both MuA and DNA
      supercoiling to the 5-noded Mu synapse built at the 3-way junction.

PMID- 15563456
TI  - Novel CAR-mediated mechanism for synergistic activation of two distinct elements
      within the human cytochrome P450 2B6 gene in HepG2 cells.
AB  - The constitutive active receptor (CAR) regulates the induction of the cytochrome
      P450 2B6 (CYP2B6) gene by phenobarbital-type inducers, such as 1,4 bis[2-(3,5
      dichloropyridyloxy)]benzene (TCPOBOP) via the distal phenobarbital-responsive
      enhancer module (PBREM, at -1732/-1685 bp). Activation of the PBREM by TCPOBOP
      generated a 10-fold induction of CYP2B6 mRNA in HepG2 cells stably expressing
      mouse CAR (Ym17). Co-treatment with the protein phosphatase inhibitor okadaic
      acid (OA) synergistically increased this induction over 100-fold without directly
      activating CAR or the PBREM. Although OA synergy required the presence of PBREM,
      deletion assays delineated the OA-responsive activity to a proximal 24-bp (-256/
      233) sequence (OARE) in the CYP2B6 promoter. CAR did not directly bind to the
      OARE in electrophoretic mobility shift assays. However, both DNA affinity and
      chromatin immunoprecipitation assays showed a significant increase in CAR
      association with the OARE after co-treatment with TCPOBOP and OA, indicating the
      indirect binding of CAR to the OARE. The two cis-acting elements, the distal
      PBREM and the proximal OARE, within the chromatin structure are both regulated by
      CAR in response to TCPOBOP and OA, respectively, to maximally induce the CYP2B6
      promoter. This functional interaction between the two sites expands the current
      understanding of the mechanism of CAR-mediated inducible transcription.

PMID- 15563457
TI  - Interaction of Fcp1 phosphatase with elongating RNA polymerase II holoenzyme,
      enzymatic mechanism of action, and genetic interaction with elongator.
AB  - Fcp1 de-phosphorylates the RNA polymerase II (RNAPII) C-terminal domain (CTD) in
      vitro, and mutation of the yeast FCP1 gene results in global transcription
      defects and increased CTD phosphorylation levels in vivo. Here we show that the
      Fcp1 protein associates with elongating RNAPII holoenzyme in vitro. Our data
      suggest that the association of Fcp1 with elongating polymerase results in CTD de
      phosphorylation when the native ternary RNAPII0-DNA-RNA complex is disrupted.
      Surprisingly, highly purified yeast Fcp1 dephosphorylates serine 5 but not serine
      2 of the RNAPII CTD repeat. Only free RNAPII0(Ser-5) and not RNAPII0-DNA-RNA
      ternary complexes act as a good substrate in the Fcp1 CTD de-phosphorylation
      reaction. In contrast, TFIIH CTD kinase has a pronounced preference for RNAPII
      incorporated into a ternary complex. Interestingly, the Fcp1 reaction mechanism
      appears to entail phosphoryl transfer from RNAPII0 directly to Fcp1. Elongator
      fails to affect the phosphatase activity of Fcp1 in vitro, but genetic evidence
      points to a functional overlap between Elongator and Fcp1 in vivo. Genetic
      interactions between Elongator and a number of other transcription factors are
      also reported. Together, these results shed new light on mechanisms that drive
      the transcription cycle and point to a role for Fcp1 in the recycling of RNAPII
      after dissociation from active genes.

PMID- 15563458
TI  - SHP-2 modulates interleukin-1-induced Ca2+ flux and ERK activation via
      phosphorylation of phospholipase Cgamma1.
AB  - Interleukin-1 (IL-1) signaling is dependent on focal adhesions, structures that
      are enriched with tyrosine kinases and phosphatases. Because the non-receptor
      tyrosine phosphatase Src homology 2 domain-containing protein tyrosine
      phosphatase-2 (SHP-2) is enriched in focal adhesions and IL-1-induced ERK
      activation requires increased Ca(2+), we determined whether SHP-2 modulates IL-1
      induced Ca(2+) signaling. In SHP-2-deficient fibroblasts, IL-1-induced Ca(2+)
      signaling and ERK activation were markedly diminished compared with cells
      expressing SHP-2. IL-1-induced Ca(2+) release from the endoplasmic reticulum
      occurred in the vicinity of focal adhesions and was strongly inhibited by the
      blockage of phospholipase C (PLC) catalytic activity. Immunoprecipitation and
      immunostaining showed that SHP-2, the endoplasmic reticulum-specific protein
      calnexin, and PLCgamma1 were associated with focal adhesions; however, these
      associations and IL-1-induced ERK activation dissipated after cells were plated
      on non-integrin substrates. IL-1 promoted phosphorylation of SHP-2 and PLCgamma1.
      IL-1-induced phosphorylation of PLCgamma1 was diminished in SHP-2-deficient cells
      but was restored by stable transfection with SHP-2. BAPTA/AM (1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester))
      blocked IL-1-induced phosphorylation of SHP-2 and PLCgamma1, indicating mutually
      dependent interactive roles for Ca(2+), SHP-2, and PLCgamma1 in IL-1 signaling.
      We conclude that SHP-2 is critical for IL-1-induced phosphorylation of PLCgamma1
      and thereby enhances IL-1-induced Ca(2+) release and ERK activation. Focal
      adhesions co-localizing with the endoplasmic reticulum may provide molecular
      staging sites required for ERK activation.

PMID- 15563459
TI  - Structural and sequence motifs in dermatan sulfate for promoting fibroblast
      growth factor-2 (FGF-2) and FGF-7 activity.
AB  - Glycosaminoglycans have been implicated in the binding and activation of a
      variety of growth factors, cytokines, and chemokines. In this way,
      glycosaminoglycans are thought to participate in events such as development and
      wound repair. In particular, heparin and heparan sulfate have been well studied,
      and specific aspects of their structure dictate their participation in a variety
      of activities. In contrast, although dermatan sulfate participates in many of the
      same biological processes as heparin and heparan sulfate, the interactions of
      dermatan sulfate have been less well studied. Dermatan sulfate is abundant in the
      wound environment and binds and activates growth factors such as fibroblast
      growth factor-2 (FGF-2) and FGF-7, which are present during the wound repair
      process. To determine the minimum size and sulfation content of active dermatan
      sulfate oligosaccharides, dermatan sulfate was first digested and then separated
      by size exclusion high pressure liquid chromatography, and the activity to
      facilitate FGF-2 and FGF-7 was assayed by the cellular proliferation of cell
      lines expressing FGFR1 or FGFR2 IIIb. The minimum size required for the
      activation of FGF-2 was an octasaccharide and for FGF-7 a decasaccharide. Active
      fractions were rich in monosulfated, primarily 4-O-sulfated, disaccharides and
      iduronic acid. Increasing the sulfation to primarily 2/4-O-sulfated and 2/6-O
      sulfated disaccharides did not increase activity. Cell proliferation decreased or
      was abolished with higher sulfated dermatan sulfate preparations. This indicated
      a preference for specific dermatan sulfate oligosaccharides capable of promoting
      FGF-2- and FGF-7-dependent cell proliferation. These data identify critical
      oligosaccharides that promote specific members of the FGF family that are
      important for wound repair and angiogenesis.

PMID- 15563460
TI  - Specificity changes in the evolution of type II restriction endonucleases: a
      biochemical and bioinformatic analysis of restriction enzymes that recognize
      unrelated sequences.
AB  - How restriction enzymes with their different specificities and mode of cleavage
      evolved has been a long standing question in evolutionary biology. We have
      recently shown that several Type II restriction endonucleases, namely SsoII
      (downward arrow CCNGG), PspGI (downward arrow CCWGG), Eco-RII (downward arrow
      CCWGG), NgoMIV (G downward arrow CCGGC), and Cfr10I (R downward arrow CCGGY),
      which recognize similar DNA sequences (as indicated, where the downward arrows
      denote cleavage position), share limited sequence similarity over an interrupted
      stretch of approximately 70 amino acid residues with MboI, a Type II restriction
      endonuclease from Moraxella bovis (Pingoud, V., Conzelmann, C., Kinzebach, S.,
      Sudina, A., Metelev, V., Kubareva, E., Bujnicki, J. M., Lurz, R., Luder, G., Xu,
      S. Y., and Pingoud, A. (2003) J. Mol. Biol. 329, 913-929). Nevertheless, MboI has
      a dissimilar DNA specificity (downward arrow GATC) compared with these enzymes.
      In this study, we characterize MboI in detail to determine whether it utilizes a
      mechanism of DNA recognition similar to SsoII, PspGI, EcoRII, NgoMIV, and Cfr10I.
      Mutational analyses and photocross-linking experiments demonstrate that MboI
      exploits the stretch of approximately 70 amino acids for DNA recognition and
      cleavage. It is therefore likely that MboI shares a common evolutionary origin
      with SsoII, PspGI, EcoRII, NgoMIV, and Cfr10I. This is the first example of a
      relatively close evolutionary link between Type II restriction enzymes of widely
      different specificities.

PMID- 15563461
TI  - Trypanosome cyclic nucleotide phosphodiesterase 2B binds cAMP through its GAF-A
      domain.
AB  - Trypanosoma brucei, the causative agent of sleeping sickness in humans and
      livestock, expresses at least three cAMP-specific class I phosphodiesterases
      (PDEs), all of which are essential for survival of the parasite. These PDEs have
      either one or two N-terminal GAF domains, which in other proteins function as
      signaling domains. However, neither the functional roles nor ligands for these
      domains in trypanosome PDEs are known. The present study shows that TbPDE2B,
      which contains two tandem GAF domains, binds cAMP with high affinity through its
      GAF-A domain. A purified recombinant N terminus + GAF-A domain binds cAMP with an
      affinity (Ki) of approximately 16 nM. It also binds cGMP but with a 15-fold lower
      affinity of approximately 275 nM. The TbPDE2B holoenzyme has a somewhat lower
      affinity (approximately 55 nM) for cAMP but a greatly lower affinity
      (approximately 10 microM) for cGMP. This suggests that both the selectivity and
      affinity for a ligand can be determined not only by the nature of the binding
      domain but also by the adjacent domains. Additionally, binding of cAMP to the
      holoenzyme showed positive cooperativity, with a Hill coefficient value of 1.75.
      However, binding of cGMP to the holoenzyme did not show any cooperativity,
      suggesting differences in the conformational changes caused by binding of these
      two cyclic nucleotides with the protein. Point mutation of a key predicted
      binding site residue (T317A) resulted in a complete loss of high affinity cAMP
      binding. This mutation increased the apparent Km of the mutant enzyme for
      substrate without altering the Vmax. A truncated catalytic domain construct of
      TbPDE2B also exhibited an increased Km, strongly suggesting that cAMP binding to
      the GAF-A domain can regulate TbPDE2B by allowing the full activity of the enzyme
      to be expressed. These properties of the GAF-A domain of TbPDE2B thus suggest
      that it could be a new target for anti-trypanosomal drugs.

PMID- 15563462
TI  - Transcriptional repression of protein kinase Calpha via Sp1 by wild type p53 is
      involved in inhibition of multidrug resistance 1 P-glycoprotein phosphorylation.
AB  - The protein kinase C (PKC) family consists of serine/threonine protein kinases
      that play important roles in signal transduction, cell proliferation, and tumor
      formation. Recent studies found that PKCs are commonly overexpressed in human
      tumors, including soft tissue sarcoma (STS). Overexpression of PKCs contributes
      to invasion and migration of tumor cells and induction of angiogenesis. PKC can
      also phosphorylate the multidrug resistance (MDR) gene-encoded P-glycoprotein and
      induce MDR phenotype. Our previous studies showed that mutation of p53 enhanced
      STS metastasis and mediated the MDR phenotype. Restoring wild type (WT) p53 in
      STS cells containing mutant p53 sensitized the cells to chemotherapy. In the
      present study, we found that PKCalpha protein expression is inhibited by WT p53
      partly due to reduced PKCalpha mRNA expression in STS cells, but p53 does not
      affect PKCalpha mRNA stability. Deletion and mutation analysis of the PKCalpha
      promoter fused to the luciferase reporter gene identified a Sp1 binding site (
      244/-234) in the PKCalpha promoter that is required for p53-mediated inhibition
      of PKCalpha promoter activity. More importantly, PKCalpha phosphorylates and
      activates MDR1 P-glycoprotein, whereas inhibition of PKCalpha by p53 leads to
      decreased MDR1 phosphorylation in STS cells, which sensitizes STS cells to
      chemotherapeutic agents. These data indicate that WT p53 may resensitize STS to
      chemotherapeutic agents by reducing MDR1 phosphorylation via transcriptional
      repression of PKCalpha expression. Thus, molecular-based therapies targeting
      mutant p53 and PKCalpha may be an effective new strategy to improve
      chemotherapeutic efficacy in STS.

PMID- 15563463
TI  - Notch signals inhibit the development of erythroid/megakaryocytic cells by
      suppressing GATA-1 activity through the induction of HES1.
AB  - The effects of Notch signals on the erythroid/megakaryocytic differentiation of
      hematopoietic cells were examined. Activation of Notch signals by the
      intracellular Notch1 or an estradiol-inducible form of Notch1/ER suppressed the
      expression of the erythroid marker glycophorin A in an erythroid/megakaryocytic
      cell line K562. Although Mock-transfected K562 cells underwent megakaryocytic
      differentiation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA),
      estradiol-activated Notch1/ER induced apoptosis during TPA treatment in the
      transfectant, which was accompanied by the reduced expression of an antiapoptotic
      molecule Bcl-XL. Even when apoptosis was prevented by the overexpression of Bcl
      XL, activated Notch signals still inhibited TPA-induced megakaryocytic
      differentiation. As for this mechanism, Notch1/recombination signal binding
      protein J-kappa-induced HES1 but not HES5 was found to inhibit the function of an
      erythroid/megakaryocytic lineage-specific transcription factor GATA-1. Although
      HES1 did not affect the DNA binding activity of GATA-1 in gel shift and chromatin
      immunoprecipitation assays, it directly bound to GATA-1 and dissociated a
      critical transcriptional cofactor, p300, from GATA-1. Furthermore, overexpressed
      HES1 inhibited the development of erythroid and megakaryocytic cells in colony
      assays. Also, the Notch ligand Jagged1 expressed on NIH3T3 cells suppressed the
      development of erythroid and megakaryocytic cells from cocultured Lin-Sca-1+
      hematopoietic stem/progenitor cells. These results suggest that Notch1 inhibits
      the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity
      through HES1.

PMID- 15563464
TI  - Functional domains of the yeast chromatin protein Sin1p/Spt2p can bind four-way
      junction and crossing DNA structures.
AB  - Sin1p/Spt2p is a yeast chromatin protein that, when mutated or deleted, alters
      the transcription of a family of genes presumably by modulating local chromatin
      structure. In this study, we investigated the ability of different domains of
      this protein to bind four-way junction DNA (4WJDNA) since 4WJDNA can serve as a
      model for bent double helical DNA and for the crossed structure formed at the
      exit and entry of DNA to the nucleosomes. Sequence alignment of Sin1p/Spt2p
      homologues from 11 different yeast species showed conservation of several
      domains. We found that three domains of Sin1p/Spt2p fused to glutathione S
      transferase can each bind independently in a structure-specific manner to 4WJDNA
      as measured in a gel mobility shift assay. A feature common to these domains is a
      cluster of positively charged amino acids. Modification of this cluster resulted
      in either abolishment of binding or a change in the binding properties. One of
      the domains tested clearly bound superhelical DNA, although it failed to induce
      bending in a circularization assay. Poly-l-lysine, which may be viewed as a
      cluster of positively charged amino acids, bound 4WJDNA as well. Phenotypic
      analysis showed that disruption of any of these domains resulted in suppression
      of a his4-912delta allele, indicating that each domain has functional
      significance. We propose that Sin1p/Spt2p is likely to modulate local chromatin
      structure by binding two strands of double-stranded DNA at their crossover point.

PMID- 15563465
TI  - A stable proteinaceous structure in the territory of inactive X chromosomes.
AB  - Transcriptional inactivation of one copy of the X chromosome in female cells
      equalizes expression of X-linked genes between males and females. This "dosage
      compensation" is a multistep process that involves epigenetic modifications of
      chromatin and is induced by the expression of a large non-coding RNA termed Xist.
      In contrast to protein-coding mRNA molecules, which are free to diffuse and roam
      the entire nuclear interior, Xist is locally constrained to the territory of
      inactive X chromosomes by as yet unclear mechanisms. Recent results have
      suggested a contribution of scaffold attachment factor A (SAF-A) in the silencing
      of X-linked genes, maybe by inducing a local change in nuclear architecture.
      Here, in vivo mobility experiments demonstrate that SAF-A is a component of a
      highly stable proteinaceous structure in the territory of inactive X chromosomes,
      which might act as a platform for immobilizing Xist RNA during the maintenance
      phase of X inactivation.

PMID- 15563466
TI  - Glycan array screening reveals a candidate ligand for Siglec-8.
AB  - Sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8) is selectively
      expressed on human eosinophils, basophils, and mast cells, where it regulates
      their function and survival. Previous studies demonstrated sialic acid-dependent
      binding of Siglec-8 but failed to reveal significant substructure specificity or
      high affinity of that binding. To test a broader range of potential ligands, a
      Siglec-8-Ig chimeric protein was tested for binding to 172 different glycan
      structures immobilized as biotinylated glycosides on a 384-well streptavidin
      coated plate. Of these, approximately 40 structures were sialylated. Among these,
      avid binding was detected to a single defined glycan, NeuAcalpha2-3(6-O
      sulfo)Galbeta1-4[Fucalpha1-3]GlcNAc, also referred to in the literature as 6'
      sulfo-sLex. Notably, neither unsulfated sLex (NeuAcalpha2-3Galbeta1-4[Fucalpha1
      3]GlcNAc) nor an isomer with the sulfate on the 6-position of the GlcNAc residue
      (6-sulfo-sLex, NeuAcalpha2-3Galbeta1-4[Fucalpha1-3](6-O-sulfo)GlcNAc) supported
      detectable binding. Subsequent secondary screening was performed using surface
      plasmon resonance. Biotin glycosides immobilized on streptavidin biosensor chips
      were exposed to Siglec-8-Ig in solution. Whereas surfaces derivatized with sLex
      and 6-sulfo-sLex failed to support detectable Siglec-8 binding, 6'-sulfo-sLex
      supported significant binding with a Kd of 2.3 microm. In a separate test of
      binding specificity, aminopropyl glycosides were covalently immobilized at
      different concentrations on activated (N-hydroxysuccinimidyl) glass surfaces
      (Schott-Nexterion Slide H). Subsequent exposure to Siglec-8-Ig precomplexed with
      fluorescein isothiocyanate anti-human Fc resulted in fluorescent signals at
      immobilized concentrations of 6'-sulfo-sLex of <5 pmol/spot. In contrast, sLex
      and 6-sulfo-sLex did not support any Siglec-8 binding at the highest
      concentration tested (300 pmol/spot). We conclude that Siglec-8 binds
      preferentially to the sLex structure bearing an additional sulfate ester on the
      galactose 6-hydroxyl.

PMID- 15563467
TI  - Domains, amino acid residues, and new isoforms of Caenorhabditis elegans
      diacylglycerol kinase 1 (DGK-1) important for terminating diacylglycerol
      signaling in vivo.
AB  - Diacylglycerol kinases (DGKs) inhibit diacylglycerol (DAG) signaling by
      phosphorylating DAG. DGK-1, the Caenorhabditis elegans ortholog of human neuronal
      DGK, inhibits neurotransmission to control behavior. DGK-1, like DGK, has three
      cysteine-rich domains (CRDs), a pleckstrin homology domain, and a kinase domain.
      To identify DGK domains and amino acid residues critical for terminating DAG
      signaling in vivo, we analyzed 20 dgk-1 mutants defective in DGK-1-controlled
      behaviors. We found by sequencing that the mutations included nine amino acid
      substitutions and seven premature stop codons that impair the physiological
      functions of DGK-1. All nine amino acid substitutions are in the second CRD, the
      third CRD, or the kinase domain. Thus, these domains are important for the
      termination of DAG signaling by DGK-1 in vivo. Seven of the substituted amino
      acid residues are present in all human DGKs and likely define key residues
      required for the function of all DGKs. An ATP-binding site mutation expected to
      inactivate the kinase domain retained very little physiological function, but we
      found two stop codon mutants predicted to truncate DGK-1 before its kinase domain
      that retained significantly more function. We detected novel splice forms of dgk
      1 that can reconcile this apparent conflict, as they skip exons containing the
      stop codons to produce DGK-1 isoforms that contain the kinase domain. Two of
      these isoforms lack an intact pleckstrin homology domain and yet appear to have
      significant function. Additional novel isoform(s) account for all of the DGK-1
      function necessary for one behavior, dopamine response.

PMID- 15563468
TI  - MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the
      polycomb group protein Bmi1.
AB  - Polycomb group (PcG) proteins form chromatin-associated, transcriptionally
      repressive complexes, which are critically involved in the control of cell
      proliferation and differentiation. Although the mechanisms involved in PcG
      mediated repression are beginning to unravel, little is known about the
      regulation of PcG function. We showed previously that PcG complexes are
      phosphorylated in vivo, which regulates their association with chromatin. The
      nature of the responsible PcG kinases remained unknown. Here we present the novel
      finding that the PcG protein Bmi1 is phosphorylated by 3pK (MAPKAP kinase 3), a
      convergence point downstream of activated ERK and p38 signaling pathways and
      implicated in differentiation and developmental processes. We identified 3pK as
      an interaction partner of PcG proteins, in vitro and in vivo, by yeast two-hybrid
      interaction and co-immunoprecipitation, respectively. Activation or
      overexpression of 3pK resulted in phosphorylation of Bmi1 and other PcG members
      and their dissociation from chromatin. Phosphorylation and subsequent chromatin
      dissociation of PcG complexes were expected to result in de-repression of
      targets. One such reported Bmi1 target is the Cdkn2a/INK4A locus. Cells
      overexpressing 3pK showed PcG complex/chromatin dissociation and concomitant de
      repression of p14(ARF), which was encoded by the Cdkn2a/INK4A locus. Thus, 3pK is
      a candidate regulator of phosphorylation-dependent PcG/chromatin interaction. We
      speculate that phosphorylation may not only affect chromatin association but, in
      addition, the function of individual complex members. Our findings linked for the
      first time MAPK signaling pathways to the Polycomb transcriptional memory system.
      This suggests a novel mechanism by which a silenced gene status can be modulated
      and implicates PcG-mediated repression as a dynamically controlled process.

PMID- 15563469
TI  - The molecular mechanisms of coactivator utilization in ligand-dependent
      transactivation by the androgen receptor.
AB  - Androgens drive sex differentiation, bone and muscle development, and promote
      growth of hormone-dependent cancers by binding the nuclear androgen receptor
      (AR), which recruits coactivators to responsive genes. Most nuclear receptors
      recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD)
      using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators
      to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N
      terminal domain (NTD) through an alternate mechanism. Here, we report that the AR
      LBD interacts with both FXXLF motifs and a subset of LXXLL motifs and that
      contacts with these LXXLL motifs are both necessary and sufficient for SRC
      mediated AR regulation of transcription. Crystal structures of the activated AR
      in complex with both recruitment motifs reveal that side chains unique to the AR
      LBD rearrange to bind either the bulky FXXLF motifs or the more compact LXXLL
      motifs and that AR utilizes subsidiary contacts with LXXLL flanking sequences to
      discriminate between LXXLL motifs.

PMID- 15563470
TI  - Pigment binding, fluorescence properties, and oligomerization behavior of Lhca5,
      a novel light-harvesting protein.
AB  - A new potential light-harvesting protein, named Lhca5, was recently detected in
      higher plants. Because of the low amount of Lhca5 in thylakoid membranes, the
      isolation of a native Lhca5 pigment-protein complex has not been achieved to
      date. Therefore, we used in vitro reconstitution to analyze whether Lhca5 binds
      pigments and is actually an additional light-harvesting protein. By this approach
      we could demonstrate that Lhca5 binds pigments in a unique stoichiometry.
      Analyses of pigment requirements for light-harvesting complex formation by Lhca5
      revealed that chlorophyll b is the only indispensable pigment. Fluorescence
      measurements showed that ligated chlorophylls and carotenoids are arranged in a
      way that allows directed energy transfer within the light-harvesting complex.
      Reconstitutions of Lhca5 together with other Lhca proteins resulted in the
      formation of heterodimers with Lhca1. This result demonstrates that Lhca5 is
      indeed a protein belonging to the light-harvesting antenna of photosystem I. The
      properties of Lhca5 are compared with those of previously characterized Lhca
      proteins, and the consequences of an additional Lhca protein for the composition
      of the light-harvesting antenna of photosystem I are discussed in view of the
      recently published photosystem I structure of the pea.

PMID- 15563471
TI  - Interdependent regulation of insulin receptor kinase activity by ADP and hydrogen
      peroxide.
AB  - Insulin signaling requires autophosphorylation of the insulin receptor kinase
      (IRK) domain. Using purified recombinant IRK fragments and the isolated intact
      insulin receptor, we show here that autophosphorylation is inhibited by ADP and
      that this effect is essentially reversed by hydrogen peroxide.
      Autophosphorylation was inhibited by hydrogen peroxide (60 microM) in the absence
      of ADP but enhanced in the presence of inhibitory concentrations of ADP (67
      microM). Enhancement by hydrogen peroxide required direct interaction of hydrogen
      peroxide with the kinase domain and was not seen in insulin receptor mutants
      C1245A and C1308A. A similar enhancement was obtained in intact cells in the
      absence of insulin upon treatment with 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1
      nitrosourea, indicating that IRK activity can be alternatively enhanced by a
      shift in the thiol/disulfide redox status. Molecular modeling of the IRK domain
      indicated that the ATP-binding site becomes distorted after releasing the
      nucleotide unless the IRK domain is oxidatively derivatized at Cys1245. Recent
      clinical studies suggest that these effects may play a role in obesity due to the
      fact that cytoplasmic creatine kinase in combination with phosphocreatine
      normally ensures rapid removal of ADP in muscle cells but not in fat cells.

PMID- 15563472
TI  - Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human
      natural killer cells.
AB  - Interleukins (IL)-2 and IL-15 regulate natural killer (NK) cell proliferation,
      survival, and cytolytic activity. Ets1 is a transcription factor expressed early
      in NK cell differentiation. Because IL-2Rbeta, IL-2Rgamma, IL-15, and Ets1 knock
      out mice similarly lack NK cells, we explored a molecular connection between IL
      2R signaling and Ets1. Here we report the post-transcriptional regulation of Ets1
      by IL-2R signaling in human NK cells. IL-2 and IL-15 stimulation leads to
      increased Ets1 protein levels with no significant change in mRNA levels. Pulse
      and pulse-chase experiments show that IL-2 stimulation results in both a marked
      increase in the nascent translation of Ets1 and an increased protein half-life.
      Pharmacological inhibition of MEK specifically blocks IL-2- and IL-15-induced
      translation, whereas p38, phosphatidylinositol 3-kinase, and mTOR inhibitors had
      no effect on Ets1 levels. Fli1, an Ets family member, exhibited a different
      mechanism of regulation, illustrating the specificity of IL-2R beta and gamma
      subunit signaling on the regulation of Ets1 expression. Expression of a dominant
      negative form of MNK1, a regulator of the translation initiation factor eIF4E,
      blocks the expression of Ets1 as do the dominant negative forms of the common IL
      2R beta and gamma chains. Expression of Ets1 is regulated similarly in normal
      peripheral human NK cells. Taken together, our findings provide a direct link
      between IL-2R subunit signaling and Ets1 expression and helps to explain the
      interdependence of the IL-2R subunits and Ets1 for NK cell development and
      function.

PMID- 15563473
TI  - Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor,
      JunD.
AB  - Mice null for menin, the product of the multiple endocrine neoplasia type 1
      (MEN1) gene, exhibit cranial and facial hypoplasia suggesting a role for menin in
      bone formation. We have shown previously that menin is required for the
      commitment of multipotential mesenchymal stem cells into the osteoblast lineage
      in part by interacting with the bone morphogenetic protein (BMP)-2 signaling
      molecules Smad1/5, and the key osteoblast transcriptional regulator, Runx2 (Sowa
      H., Kaji, H., Hendy, G. N., Canaff, L., Komori, T., Sugimoto, T., and Chihara, K.
      (2004) J. Biol. Chem. 279, 40267-40275). However, menin inhibits the later
      differentiation of committed osteoblasts. The activator protein-1 (AP-1)
      transcription factor, JunD, is expressed in osteoblasts and has been shown to
      interact with menin in other cell types. Here, we examined the consequences of
      menin-JunD interaction on osteoblast differentiation in mouse osteoblastic MC3T3
      E1 cells. JunD expression, assessed by immunoblot, gradually increased during
      osteoblast differentiation. Stable expression of JunD enhanced expression of the
      differentiation markers, Runx2, type 1 collagen (COL1), and osteocalcin (OCN) and
      alkaline phosphatase (ALP) activity and mineralization. Hence, JunD promotes
      osteoblast differentiation. In MC3T3-E1 cells in which menin expression was
      reduced by stable menin antisense DNA transfection, JunD levels were increased.
      When JunD and menin were co-transfected in MC3T3-E1 cells, they co
      immunoprecipitated. JunD overexpression increased the transcriptional activity of
      an AP-1 luciferase reporter construct, and this activity was reduced by co
      transfection of menin. Therefore, JunD and menin interact both physically and
      functionally in osteoblasts. Furthermore, menin overexpression inhibited the ALP
      activity induced by JunD. In conclusion, the data suggest that menin suppresses
      osteoblast maturation, in part, by inhibiting the differentiation actions of
      JunD.

PMID- 15563475
TI  - Application of commercial calibrators for the analysis of immunosuppressant drugs
      in whole blood.

PMID- 15563476
TI  - Validation by a mass spectrometric reference method of use of boronate affinity
      chromatography to measure glycohemoglobin in the presence of hemoglobin S and C
      traits.

PMID- 15563477
TI  - Cardiac troponin and creatine kinase MB monitoring during in-hospital myocardial
      reinfarction.

PMID- 15563478
TI  - Plasma concentrations of cystatin C in patients with coronary heart disease and
      risk for secondary cardiovascular events: more than simply a marker of glomerular
      filtration rate.
AB  - BACKGROUND: Renal impairment (RI) is associated with worse prognosis. Recently,
      cystatin C has been shown to represent a potentially superior marker of the
      glomerular filtration rate compared with creatinine clearance (CrCl). We
      evaluated the impact of cystatin C and other markers of RI on prognosis in a
      large cohort of patients with coronary heart disease (CHD). METHODS: Cystatin C,
      creatinine (Cr), and CrCl were determined at baseline in a cohort of 1033
      patients (30-70 years) with CHD. Patients were followed for a mean of 33.5
      months, and a combined endpoint [fatal and nonfatal cardiovascular disease (CVD)
      events] was used as the outcome variable. Cystatin C was measured by
      immunonephelometry, and CrCl was calculated. RESULTS: During follow-up, 71
      patients (6.9%) experienced a secondary CVD event. Neither Cr (P = 0.63) nor CrCl
      (P = 0.10) were associated with incidence of CVD events, whereas cystatin C was
      clearly associated with risk of secondary CVD events (P <0.0001). In multivariate
      analyses, patients in the top quintile of the cystatin C distribution at baseline
      had a statistically significantly increased risk of secondary CVD events even
      after adjustment for classic risk factors, severity of coronary disease, history
      of diabetes mellitus, treatment with angiotensin-converting enzyme inhibitors,
      and C-reactive protein (hazard ratio, 2.27; 95% confidence interval, 1.05-4.91)
      compared with patients in the bottom quintile. CONCLUSIONS: These data support
      the possibly important prognostic value of cystatin C among patients with known
      CHD and suggest that it may be a useful clinical marker providing complementary
      information to established risk determinants.

PMID- 15563479
TI  - Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated tau
      (Thr181) in cerebrospinal fluid by the xMAP technology.
AB  - BACKGROUND: To simultaneously study several biomarkers for Alzheimer disease
      (AD), we used the xMAP technology to develop and evaluate a multiparametric bead
      based assay for quantification of beta-amyloid((1-42)) [Abeta((1-42))], total tau
      (T-TAU), and hyperphosphorylated tau [P-TAU((181P))] in cerebrospinal fluid
      (CSF). METHODS: We compared the new multianalyte assay format with established
      ELISA techniques for the same proteins. We then performed a clinical study using
      CSF samples from patients with AD or mild cognitive impairment with progression
      to AD, healthy controls, and patients with other neurologic disorders. RESULTS:
      The INNO-BIA AlzBio3 selectively and specifically measured Abeta((1-42)), T-TAU,
      and P-TAU((181P)) in the CSF. The new assay format had intra- and interassay CVs
      <10% for all analytes, even at low concentrations. The measurement range of the
      new assay was 3 to 4 logs compared with 1 to 2 logs for ELISAs. By plotting the
      mean of the values obtained in ELISA and the xMAP technology against the
      difference, we found that a correction factor could be used to convert xMAP
      results to ELISA values. The clinical study demonstrated that the new
      multiparametric assay could accurately distinguish patients with AD from patients
      with other neurologic disorders or control patients, with the diagnostic accuracy
      reaching recommended consensus criteria for specificity and sensitivity.
      CONCLUSION: The new multiparametric method may be able to replace the
      corresponding ELISA methods.

PMID- 15563480
TI  - Assay-specific decision limits for two new automated parathyroid hormone and 25
      hydroxyvitamin D assays.
AB  - BACKGROUND: The recent development of nonradioactive automated assays for serum
      parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) has made measurement of
      these two hormones possible in many laboratories. In this study, we compared two
      new assays for PTH and 25OHD adapted on an automated analyzer, the LIAISON, with
      two manual immunoassays used worldwide. METHODS: We studied 228 osteoporotic
      patients, 927 healthy individuals, 38 patients with primary hyperparathyroidism,
      and 167 hemodialyzed patients. Serum PTH was measured with the Allegro and the
      LIAISON assays, and 25OHD was measured with DiaSorin RIA and the LIAISON assay.
      Regression analysis was used to calculate decision thresholds for the LIAISON
      assays that were equivalent to those of the Allegro PTH and DiaSorin 25OHD
      assays. RESULTS: The 25OHD concentrations obtained with the LIAISON assay and the
      RIA in osteoporotic patients were well correlated (r = 0.83; P <0.001).
      Regression and Bland-Altman analyses suggested that the LIAISON 25OHD assay reads
      lower than the DiaSorin RIA at low concentrations but higher at high
      concentrations. However, the cutoff (50 nmol/L) used in our laboratories to
      define vitamin D insufficiency with the DiaSorin RIA is applicable to the LIAISON
      25OHD assay. In 927 healthy individuals, the 3rd-97th percentile intervals were 3
      80 ng/L and 13-151 nmol/L for the LIAISON PTH and 25OHD concentrations,
      respectively. However, 506 individuals (54.6%) were vitamin D-insufficient; we
      therefore considered only the 421 individuals with a LIAISON 25OHD >50 nmol/L as
      eligible for the reference population for the LIAISON PTH assay. In this group,
      the 3rd-97th percentile interval for LIAISON PTH was 3-51 ng/L. Considering upper
      reference limits of 46 and 51 ng/L for the Allegro and LIAISON assays,
      respectively, the frequency of above-normal PTH concentrations in patients with
      primary hyperparathyroidism was similar in both assays. Regression analysis
      between serum PTH measured by the Allegro and LIAISON assays in 167 hemodialyzed
      patients and the corresponding Bland-Altman analysis of these data suggest that
      the LIAISON PTH assay tends to read higher than the Allegro assay at low
      concentrations but lower at high concentrations (>300 ng/L). CONCLUSIONS: Because
      clinical decision limits for both PTH and 25OHD should be assay specific, we
      propose equivalences between these assays and two manual assays used worldwide.
      These assay-specific decision limits should help potential users of the LIAISON
      PTH and 25OHD assays.

PMID- 15563481
TI  - Development of miniaturized competitive immunoassays on a protein chip as a
      screening tool for drugs.
AB  - BACKGROUND: Doping in sports has become a serious problem. Gas chromatography
      mass spectrometry (GC-MS) serves as an effective reference method, but it is
      limited by low throughput and is therefore not suitable for large-scale
      screening. Use of protein chips for high-throughput screening of all athletes for
      prohibited substances could become an important complementary tool to GC-MS.
      METHODS: We developed a protein chip based on an aldehyde-activated glass slide
      containing 10 physically isolated arrays. The chip was used to screen urine from
      1347 athletes for prohibited substances and to screen a negative control group
      consisting of 200 females and 120 males. Urine samples from 66 individuals known
      to be abusers, provided by the China Doping Control Center (CDCC), and 129
      standard prohibited substances were tested as positive controls. RESULTS: All
      1347 urine samples screened by means of the protein chips were also subjected to
      reference analysis by GC-MS at the CDCC. There was no qualitative difference
      between the results obtained with the two methods. The correlation coefficient
      (r(2)) for the quantitative results obtained with the protein chip and GC-MS was
      0.991. CONCLUSIONS: The protein chip could be used to screen for a series of 16
      prohibited drugs in urine samples. This system has the potential to become an
      effective screening method to test substances prohibited by the International
      Olympic Committee.

PMID- 15563482
TI  - Cardiac biomarkers in renal disease: the fog is slowly lifting.

PMID- 15563483
TI  - Noninvasive photonic-crystal material for sensing glucose in tears.

PMID- 15563484
TI  - New form of urinary albumin in early diabetes.

PMID- 15563485
TI  - Validation of the calcineurin phosphatase assay.
AB  - BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are used as
      primary immunosuppressive drugs in transplant patients. Measuring calcineurin
      phosphatase (CaN) activity is a proposed pharmacodynamic approach to optimize
      dosing of these drugs. METHODS: Whole blood samples were obtained from 10
      patients treated with calcineurin inhibitors and 20 healthy volunteers and frozen
      at -80 degrees C. CaN activity was measured by its ability to dephosphorylate a
      19-amino acid peptide previously phosphorylated with [gamma-(32)P]ATP.
      Radioactivity was quantified by liquid scintillation, and results were converted
      from cpm to U of CaN. Validation of the assay included enzyme kinetics,
      linearity, precision (at low and normal CaN activities), analytical recovery, and
      limit of detection. RESULTS: The enzyme followed simple Michaelis-Menten-type
      kinetics: V(max) was estimated as 240 nmol (32)P x L(-1) x min(-1) and K(m) as 70
      micromol/L. The assay was linear within the concentration range examined.
      Analytical recovery varied from 68% to 72%. The total analytical SD was 0.059 and
      0.053 U of CaN for high and low CaN activity, respectively. The within-day SD for
      high and low activity was 0.032 and 0.039 U of CaN, respectively. The limit of
      detection was 0.04 U of CaN, which is far below the values measured in patients
      treated with CaN inhibitors. CONCLUSIONS: In addition to the pharmacokinetic
      monitoring applied today, the CaN assay can be used to monitor patients treated
      with calcineurin inhibitors, hopefully leading to prolonged graft survival.

PMID- 15563486
TI  - Alternative approach for rapid and reliable single-nucleotide polymorphism typing
      with double restriction mutagenesis primer PCR.

PMID- 15563487
TI  - Nonparametric determination of reference intervals for plasma metanephrine and
      normetanephrine.

PMID- 15563488
TI  - Gene expression profiles in formalin-fixed, paraffin-embedded tissues obtained
      with a novel assay for microarray analysis.

PMID- 15563489
TI  - Cerebrospinal fluid activin a measurement in asphyxiated full-term newborns
      predicts hypoxic ischemic encephalopathy.

PMID- 15563490
TI  - Within-person, among-finger variability of capillary blood glucose measurements.

PMID- 15563491
TI  - Pyrosequencing method for genotyping cytochrome P450 CYP2C8 and CYP2C9 enzymes.

PMID- 15563492
TI  - CYP2C9*2 and CYP2C9*3 alleles confer a lower risk for myocardial infarction.

PMID- 15563493
TI  - Potential interferences from blood collection tubes in mass spectrometric
      analyses of serum polypeptides.

PMID- 15563494
TI  - Genotyping of hepatitis C virus by melting curve analysis: analytical
      characteristics and performance.

PMID- 15563495
TI  - ELISA for specific detection of PiZ-related alpha(1)-antitrypsin deficiency.

PMID- 15563496
TI  - Problem with detection of an insertion-type mutation in the BCHE gene in a
      patient with butyrylcholinesterase deficiency.

PMID- 15563497
TI  - Monitoring of hematopoietic chimerism by short tandem repeats, and the effect of
      CD selection on its sensitivity.

PMID- 15563498
TI  - Clinical chemistry through Clinical Chemistry: a journal timeline.
AB  - The establishment of the modern discipline of clinical chemistry was concurrent
      with the foundation of the journal Clinical Chemistry and that of the American
      Association for Clinical Chemistry in the late 1940s and early 1950s. To mark the
      50th volume of this Journal, I chronicle and highlight scientific milestones, and
      those within the discipline, as documented in the pages of Clinical Chemistry.
      Amazing progress has been made in the field of laboratory diagnostics over these
      five decades, in many cases paralleling-as well as being bolstered by-the rapid
      pace in the development of computer technologies. Specific areas of laboratory
      medicine particularly well represented in Clinical Chemistry include lipids,
      endocrinology, protein markers, quality of laboratory measurements, molecular
      diagnostics, and general advances in methodology and instrumentation.

PMID- 15563499
TI  - More on premetrologic variation.

PMID- 15563500
TI  - Stability of whole blood at -70 degrees C for measurement of hemoglobin A(1c) in
      healthy individuals.

PMID- 15563501
TI  - Increased frequency of the MTHFR A1298C mutation in an Irish population.

PMID- 15563502
TI  - Interference in measurement of potassium caused by bacterial contamination of an
      analyzer.

PMID- 15563503
TI  - Endocrine paradox in heart failure: resistance to biological effects of cardiac
      natriuretic hormones.

PMID- 15563504
TI  - Reference values for N-terminal pro-B-type natriuretic peptide in umbilical cord
      blood.

PMID- 15563506
TI  - Dominant collagen VI mutations are a common cause of Ullrich congenital muscular
      dystrophy.
AB  - Mutations in the three collagen VI genes COL6A1, COL6A2 and COL6A3 cause Bethlem
      myopathy and Ullrich congenital muscular dystrophy (UCMD). UCMD, a severe
      disorder characterized by congenital muscle weakness, proximal joint contractures
      and marked distal joint hyperextensibility, has been considered a recessive
      condition, and homozygous or compound heterozygous mutations have been defined in
      COL6A2 and COL6A3. In contrast, the milder disorder Bethlem myopathy shows clear
      dominant inheritance and is caused by heterozygous mutations in COL6A1, COL6A2
      and COL6A3. This model, where dominant mutations cause mild Bethlem myopathy and
      recessive mutations cause severe UCMD was recently challenged when a patient with
      UCMD was shown to have a heterozygous in-frame deletion in COL6A1. We have
      studied five patients with a clinical diagnosis of UCMD. Three patients had
      heterozygous in-frame deletions in the N-terminal region of the triple helical
      domain, one in the alpha1(VI) chain, one in alpha2(VI) and one in alpha3(VI).
      Collagen VI protein biosynthesis and assembly studies showed that these mutations
      act in a dominant negative fashion and result in severe collagen VI matrix
      deficiencies. One patient had recessive amino acid changes in the C2 subdomain of
      alpha2(VI), which prevented collagen VI assembly. No collagen VI mutations were
      found in the fifth patient. These data demonstrate that rather than being a rare
      cause of UCMD, dominant mutations are common in UCMD, now accounting for four of
      the 14 published cases. Mutation detection in this disorder remains critical for
      accurate genetic counseling of patients and their families.

PMID- 15563507
TI  - Molecular dissection of the events leading to inactivation of the FMR1 gene.
AB  - The analysis of a lymphoblastoid cell line (5106), derived from a rare individual
      of normal intelligence with an unmethylated full mutation of the FMR1 gene,
      allowed us to reconstruct the chain of molecular events leading to the FMR1
      inactivation and to fragile X syndrome. We found that lack of DNA methylation of
      the entire promoter region, including the expanded CGG repeat, correlates with
      methylation of lysine 4 residue on the N-tail of histone H3 (H3-K4), as in normal
      controls. Normal levels of FMR1 mRNA were detected by real-time fluorescent RT
      PCR (0.8-1.4 times compared with a control sample), but mRNA translation was less
      efficient (-40%), as judged by polysome profiling, resulting in reduced levels of
      FMRP protein (approximately 30% of a normal control). These results underline
      once more that CGG repeat amplification per se does not prevent FMR1
      transcription and FMRP production in the absence of DNA methylation.
      Surprisingly, we found by chromatin immunoprecipitation that cell line 5106 has
      deacetylated histones H3 and H4 as well as methylated lysine 9 on histone H3 (H3
      K9), like fragile X cell lines, in both the promoter and exon 1. This indicates
      that these two epigenetic marks (i.e. histone deacetylation and H3-K9
      methylation) can be established in the absence of DNA methylation and do not
      interfere with active gene transcription, contrary to expectation. Our results
      also suggest that the molecular pathways regulating DNA and H3-K4 methylation are
      independent from those regulating histone acetylation and H3-K9 methylation.

PMID- 15563508
TI  - Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal
      photoreceptor degeneration.
AB  - Retina and retinal pigment epithelium (RPE) belong to the metabolically most
      active tissues in the human body. Efficient removal of acid load from retina and
      RPE is a critical function mediated by the choriocapillaris. However, the
      mechanism by which pH homeostasis is maintained is largely unknown. Here, we show
      that a functional complex of carbonic anhydrase 4 (CA4) and Na+/bicarbonate co
      transporter 1 (NBC1) is specifically expressed in the choriocapillaris and that
      missense mutations in CA4 linked to autosomal dominant rod-cone dystrophy disrupt
      NBC1-mediated HCO3- transport. Our results identify a novel pathogenic pathway in
      which a defect in a functional complex involved in maintaining pH balances, but
      not expressed in retina or RPE, leads to photoreceptor degeneration. The
      importance of a functional CA4 for survival of photoreceptors implies that CA
      inhibitors, which are widely used as medications, particularly in the treatment
      of glaucoma, may have long-term adverse effects on vision.

PMID- 15563509
TI  - Altered expression of mitochondria-related genes in postmortem brains of patients
      with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray
      analysis.
AB  - Accumulating evidence suggests that mitochondrial dysfunction underlies the
      pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed
      large-scale DNA microarray analysis of postmortem brains of patients with BD or
      SZ, and examined expression patterns of mitochondria-related genes. We found a
      global down-regulation of mitochondrial genes, such as those encoding respiratory
      chain components, in BD and SZ samples, even after the effect of sample pH was
      controlled. However, this was likely due to the effects of medication. Medication
      free patients with BD showed tendency of up-regulation of subset of mitochondrial
      genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ
      pathologies. However, it may be the expression changes of a small fraction of
      mitochondrial genes rather than the global down-regulation of mitochondrial
      genes. Our findings warrant further study of the molecular mechanisms underlying
      mitochondrial dysfunction in BD and SZ.

PMID- 15563510
TI  - Low levels of microsatellite instability characterize MLH1 and MSH2 HNPCC
      carriers before tumor diagnosis.
AB  - Microsatellite instability (MSI) characterizes tumors arising in patients with
      hereditary non-polyposis colorectal cancer (HNPCC) syndrome. HNPCC is a
      hereditary autosomal dominant disease caused by germline mutations in genes from
      the DNA (MMR) mismatch repair system. In these tumors, the loss of MMR
      compromises the genome integrity, allowing the progressive accumulation of
      mutations and the establishment of a mutator phenotype in a recessive manner. It
      is not clear, however, whether MSI can be detected in HNPCC carriers before tumor
      diagnosis. The aim of this study was to evaluate the presence of genetic
      instability in MMR gene carriers in peripheral blood lymphocytes of carriers and
      non-carriers members of two HNPCC families harboring a germline MLH1 and MSH2
      mutation, respectively. An extensive analysis of the allelic distribution of
      single molecules of the polyA tract bat26 was performed using a highly sensitive
      PCR-cloning approach. In non-carriers, the allelic distribution of single bat26
      molecules followed a gaussian distribution with no bat26 alleles shorter than
      (A)21. All mutation carriers showed unstable alleles [(A)20 or shorter] with an
      overall frequency of 5.6% (102/1814). We therefore suggest that low levels of
      genomic instability characterize MMR mutation carriers. These observations
      suggest that somatic mutations accumulate well before tumor diagnosis. Even
      though it is not clear whether this is due to the presence of a small percentage
      of cells with lost MMR or due to MMR haploinsufficiency, detection of these short
      unstable alleles might help in the identification of asymptomatic carriers
      belonging to families with no detectable MMR gene mutations.

PMID- 15563511
TI  - Strand bias in oligonucleotide-mediated dystrophin gene editing.
AB  - Defects in the dystrophin gene cause the severe degenerative muscle disorder,
      Duchenne muscular dystrophy (DMD). Among the gene therapy approaches to DMD under
      investigation, a gene editing approach using oligonucleotide vectors has yielded
      encouraging results. Here, we extend our studies of gene editing with self
      pairing, chimeric RNA/DNA oligonucleotides (RDOs) to the use of
      oligodeoxynucleotides (ODNs) to correct point mutations in the dystrophin gene.
      The ODN vectors offer many advantages over the RDO vectors, and we compare the
      targeting efficiencies in the mdx(5cv) mouse model of DMD. We found that ODNs
      targeted to either the transcribed or the non-transcribed strand of the
      dystrophin gene were capable of inducing gene repair, with efficiencies
      comparable to that seen with RDO vectors. Oligonucleotide-mediated repair was
      demonstrated at the genomic, mRNA and protein levels in muscle cells both in
      vitro and in vivo, and the correction was stable over time. Interestingly, there
      was a strand bias observed with the ODNs, with more efficient correction of the
      non-transcribed strand even though the dystrophin gene is not transcribed in
      proliferating myoblasts. This finding demonstrates that strand bias of ODN
      mediated gene repair is likely to be due to the specific sequence of the target
      gene in addition to any effects of transcription. A better understanding of how
      the efficiency of gene editing relates to the target sequence will offer the
      opportunity for rational oligonucleotide design for further development of this
      elegant approach to gene therapy for DMD and other genetic diseases.

PMID- 15563512
TI  - Progression from frontal-parietal to mesial-temporal epilepsy after fluid
      percussion injury in the rat.
AB  - We recently described an in vivo model of post-traumatic epilepsy (PTE) in the
      rat where chronic spontaneous recurrent seizures appear following a single
      episode of fluid percussion injury (FPI). PTE, studied during the first 2 months
      post-injury, was focal and seizures originated predominantly from the frontal
      parietal neocortex at or around the injury site. However, rarer bilateral
      seizures originating from a different and undefined focus were also observed. To
      shed light on the Posttraumatic Epileptogenic mechanisms and on the generation of
      bilateral seizures, we studied rats up to 7 months post-injury. In vivo paired
      epidural and depth-electrode recordings indicated that the anterior hippocampus
      evolves into an epileptic focus which initiates bilateral seizures. The rate of
      frontal-parietal seizures remained constant over time after 2 weeks post-injury,
      while the rate of hippocampal seizures greatly increased over time, suggesting
      that different mechanisms mediate neocortical and hippocampal post-traumatic
      epileptogenesis. Because of different temporal evolution of these foci, the
      epileptic syndrome was characterized by predominant frontal-parietal seizures
      early after injury, but by predominant mesio-temporal seizures at later time
      points. Pathological analysis demonstrated progressive hippocampal and temporal
      cortex pathology that paralleled the increase in frequency and duration of
      bilateral seizures. These results demonstrate that FPI-induced frontal-parietal
      epilepsy (FPE) progresses to mesial-temporal lobe epilepsy (MTLE) with dual
      pathology. These observations establish numerous similarities between FPI-induced
      and human PTE and further validate it as a clinically relevant model of PTE.

PMID- 15563513
TI  - Somatosensory evoked high-frequency oscillations reflecting thalamo-cortical
      activity are decreased in migraine patients between attacks.
AB  - A deficit of habituation in cortical information processing, including
      somatosensory evoked potentials (SSEPs), is the most consistent
      neurophysiological abnormality in migraine patients between attacks. To explore
      further the mechanisms underlying this interictal neural dysfunction, we have
      studied the high-frequency oscillations (HFOs) embedded in SSEPs because they are
      thought to reflect spike activity in thalamo-cortical cholinergic fibres (early
      HFOs) and in cortical inhibitory GABAergic interneurons (late HFOs). Untreated
      migraine patients with (MA) and without (MO) aura were recorded during (n = 13:
      nine MO, four MA) and between attacks (n = 29: 14 MO, 15 MA) and compared with
      healthy volunteers. SSEPs were filtered off-line (digital band-pass between 450
      and 750 Hz) to extract the two HFO bursts from the broad-band contralateral N20
      somatosensory cortical response obtained by median nerve stimulation. In both
      migraine groups, amplitudes and latencies of conventional broad-band SSEPs
      recorded interictally from cervical and parietal active electrodes were not
      significantly different from those found in healthy volunteers. In contrast,
      maximum peak-to-peak amplitude and area under the rectified curve of the early
      HFO burst were significantly smaller in both MA and MO patients than in healthy
      volunteers. There was no significant difference in the later HFO burst between
      migraineurs and healthy volunteers. During attacks, all electrophysiological
      measurements in migraineurs were similar to those found in healthy volunteers.
      Thalamo-cortical activation, as reflected by the early SSEP HFO burst, may thus
      be reduced in migraine interictally, but normalizes during an attack, whereas
      intracortical inhibition, as indexed by the late HFO burst, is normal at any
      time. This supports the hypothesis that the habituation deficit in migraineurs is
      due to a reduced pre-activation level of sensory cortices and not to increased
      cortical excitability or reduced intracortical inhibition.

PMID- 15563514
TI  - Utilization of magnetoencephalography results to obtain favourable outcomes in
      epilepsy surgery.
AB  - Magnetoencephalography (MEG) is a well-known technique in the presurgical
      evaluation of epilepsy patients. Like EEG, it can detect and localize epileptic
      activity. Epilepsy surgery can be used to evaluate MEG source localizations.
      Resection volumes were determined in 33 epilepsy surgery patients. The resection
      volume, taken together with the post-operative outcome, was used to evaluate MEG
      results. The scattering MEG localizations of interictal epileptic activity were
      represented by an ellipsoidal volume. Using this MEG results ellipsoid, it was
      demonstrated that a high coverage by the resection volume and a small distance to
      the resection volume are both correlated to a favourable outcome; in addition, a
      homogeneous distribution of MEG localizations is correlated to a favourable
      outcome. This study shows that MEG source localization can help to delineate
      epileptic activity and, along with other techniques, should be taken into account
      for epilepsy surgery.

PMID- 15563515
TI  - Brain asymmetries in autism and developmental language disorder: a nested whole
      brain analysis.
AB  - We report a whole-brain MRI morphometric survey of asymmetry in children with
      high-functioning autism and with developmental language disorder (DLD). Subjects
      included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD,
      15 controls). Imaging analysis included grey-white segmentation and cortical
      parcellation. Asymmetry was assessed at a series of nested levels. We found that
      asymmetries were masked with larger units of analysis but progressively more
      apparent with smaller units, and that within the cerebral cortex the differences
      were greatest in higher-order association cortex. The larger units of analysis,
      including the cerebral hemispheres, the major grey and white matter structures
      and the cortical lobes, showed no asymmetries in autism or DLD and few
      asymmetries in controls. However, at the level of cortical parcellation units,
      autism and DLD showed more asymmetry than controls. They had a greater aggregate
      volume of significantly asymmetrical cortical parcellation units (leftward plus
      rightward), as well as a substantially larger aggregate volume of right
      asymmetrical cortex in DLD and autism than in controls; this rightward bias was
      more pronounced in autism than in DLD. DLD, but not autism, showed a small but
      significant loss of leftward asymmetry compared with controls. Right : left
      ratios were reversed, autism and DLD having twice as much right- as left
      asymmetrical cortex, while the reverse was found in the control sample. Asymmetry
      differences between groups were most significant in the higher-order association
      areas. Autism and DLD were much more similar to each other in patterns of
      asymmetry throughout the cerebral cortex than either was to controls; this
      similarity suggests systematic and related alterations rather than random neural
      systems alterations. We review these findings in relation to previously reported
      volumetric features in these two samples of brains, including increased total
      brain and white matter volumes and lack of increase in the size of the corpus
      callosum. Larger brain volume has previously been associated with increased
      lateralization. The sizeable right-asymmetry increase reported here may be a
      consequence of early abnormal brain growth trajectories in these disorders, while
      higher-order association areas may be most vulnerable to connectivity
      abnormalities associated with white matter increases.

PMID- 15563516
TI  - Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus
      fumigatus serially isolated from a patient with lung aspergilloma.
AB  - OBJECTIVES: To monitor changes in itraconazole susceptibility of isolates from a
      patient undergoing treatment for pulmonary Aspergillus infection and relate these
      changes to genotypic/phenotypic alterations. METHODS: Six Aspergillus fumigatus
      isolates were serially recovered from the patient. Itraconazole MICs were
      determined by Etest and NCCLS methodology. Growth characteristics and phenotype
      were monitored. Molecular analysis included random amplified polymorphic DNA
      (RAPD) assay and sequencing of the cyp51A gene. RESULTS: The MIC of itraconazole
      against the first isolate before treatment was 0.25 mg/L; the MIC against the
      second isolate, recovered after 6 months of itraconazole therapy, was >16 mg/L;
      and that against the third isolate, obtained 2 months after discontinuation of
      the therapy, was 0.5 mg/L. The MIC against the last three isolates, acquired
      after restoration of itraconazole therapy for 4-7 months, was >16 mg/L. The six
      isolates shared identical band patterns of RAPD assay using four primers and the
      same sequence in intertranscribed spacers (ITS). Therefore, the six isolates were
      likely to be the same strain of A. fumigatus, and mutations involving
      itraconazole resistance possibly occurred in these isolates after prolonged
      itraconazole therapy. Sequencing of the cyp51A gene in the coding region revealed
      a mutation of M220I in cytochrome P450 sterol 14-alpha-demethylase in the second
      resistant isolate and a mutation of G54R in the last three resistant isolates.
      Expression changes of some pump genes, such as MDR3, may also, in part, be
      related to the resistance to itraconazole. CONCLUSIONS: We conclude that
      resistance of A. fumigatus to itraconazole occurred in a patient treated with the
      drug, and the resistance may result from mutations in the cyp51A gene-the gene
      encoding the target enzyme for itraconazole.

PMID- 15563517
TI  - Pharmacodynamic studies of amoxicillin against Streptococcus pneumoniae:
      comparison of a new pharmacokinetically enhanced formulation (2000 mg twice
      daily) with standard dosage regimens.
AB  - OBJECTIVES: To compare the pharmacodynamic effects of a pharmacokinetically
      enhanced formulation of amoxicillin 2000 mg twice daily, with amoxicillin 875 mg
      twice daily, 875 mg three times daily and 500 mg three times daily against
      Streptococcus pneumoniae with different susceptibility to amoxicillin in an in
      vitro kinetic model. METHODS: Strains of S. pneumoniae with amoxicillin MICs of
      1, 2, 4 and 8 mg/L at an initial inoculum of approximately 10(5) cfu/mL were
      exposed to amoxicillin in an in vitro kinetic model simulating the human serum
      concentration-time profile of the pharmacokinetically enhanced formulation twice
      daily (C(max) 17 mg/L after 1.5 h). All isolates were also exposed to amoxicillin
      with concentration-time profiles correlating to the human dosage of 875 mg twice
      daily (C(max) 15 mg/L after 1 h), 875 mg three times daily and 500 mg (C(max) 8
      mg/L after 1 h) three times daily with simulated half-life of 1 h. Repeated
      samples were taken regularly during 24 h and viable counts were carried out.
      RESULTS: Overall, the pharmacokinetically enhanced formulation was more effective
      at reducing bacterial counts than any of the other formulations evaluated.
      Eradication was achieved with the enhanced formulation for strains with a MIC of
      < or =2 mg/L, however, regrowth occurred with the other dosing regimens. In the
      experiments with the strain with a MIC of 4 mg/L, the enhanced formulation kept
      the bacterial counts < or =10(2) cfu/mL for at least 14 out of 24 h tested. In
      contrast, none of the other formulations reduced the bacterial counts down to <
      or =10(2) cfu/mL at any point. None of the regimens was able to eradicate the
      strain with an MIC of 8 mg/L, even though an initial substantial kill was noted
      with the enhanced formulation after both doses. The least effective dosage
      regimen for all strains was 875 mg twice daily.

PMID- 15563518
TI  - Distribution and molecular analysis of mef(A)-containing elements in tetracycline
      susceptible and -resistant Streptococcus pyogenes clinical isolates with efflux
      mediated erythromycin resistance.
AB  - OBJECTIVES: To analyse the distribution and molecular features of mef(A)
      containing elements in a large collection of different Streptococcus pyogenes
      clinical isolates with efflux-mediated erythromycin resistance. To further
      characterize a tet(O)-mef(A) element. METHODS: Gene detection was carried out by
      PCR using primers designed from established sequences or from sequences in this
      study. From a tet(O)-mef(A) element (approximately 60 kb), an 11 972 bp region
      including the tet(O) and mef(A) genes was sequenced. RESULTS: In the tetracycline
      susceptible isolates (n =28), the mef(A) gene was contained in a regular Tn1207.1
      transposon (7.2 kb), which was inserted into one of two previously described
      elements, Tn1207.3 (approximately 52 kb) or a 58.8 kb chimeric element, both
      flanked by the comEC gene. In the tetracycline-resistant isolates (n =61), all of
      which carried the tet(O) gene, the mef(A) gene was part of a variable Tn1207.1
      related transposon inserted into unique elements which contained the tet(O) gene
      approximately 2.3 to 5.5 kb upstream of the mef(A) gene and were not flanked by
      the comEC gene. In the Tn1207.1-like transposon of these tet(O)-mef(A) elements,
      only msr(D) (orf5) and a modified orf6, in addition to mef(A), were detected by
      PCR in all isolates tested; while orf1 and orf2 were always undetectable, orf3,
      orf7 and orf8 were found in variable percentages. In an orf3-positive element,
      sequencing identified four new open reading frames downstream of the tet(O) gene,
      followed by three short sequences with homology to sequences of the pneumococcal
      mega element. CONCLUSIONS: The mef(A) gene is carried on different chromosomal
      genetic elements depending on whether the isolates are susceptible or resistant
      to tetracycline.

PMID- 15563519
TI  - Viridans streptococci in endocarditis and neutropenic sepsis: biofilm formation
      and effects of antibiotics.
AB  - OBJECTIVES: Viridans group streptococci (VGS) are a frequent cause of bacterial
      endocarditis or sepsis in patients with neutropenia. Endocarditis in particular,
      is associated with plaque formation on the endocardium and valve leaflets whereas
      VGS septicaemia in neutropenic patients is caused by the influx of oral flora
      bacteria through mucositic lesions. This study examined the in vitro potency for
      biofilm formation of clinical VGS bloodstream isolates, and the effects of
      antibiotics on these biofilms. METHODS: During the years 1998-2000, 40 VGS
      bloodstream isolates from 18 patients with endocarditis and 22 patients with
      severe sepsis and neutropenia were collected. The MICs of penicillin, teicoplanin
      and moxifloxacin were determined using the microdilution broth method according
      to NCCLS criteria. Biofilms were grown in microtitre plates, dyed with Crystal
      Violet, and the mean optical density (OD) was used for quantification. Biofilms
      were incubated with penicillin, teicoplanin and moxifloxacin at various
      concentrations starting with the MICs for the respective isolates tested.
      RESULTS: Isolates from eight out of 18 patients with endocarditis and six out of
      22 patients with neutropenia formed biofilms (not significant). For the 14
      isolates, the MIC(90)s (range) of penicillin, teicoplanin and moxifloxacin were
      0.5 mg/L (0.001-0.5), 0.125 mg/L (0.025-0.125) and 0.5 mg/L (0.05-0.5),
      respectively. Generally, biofilms persisted although incubated with the
      antibiotics up to concentrations of 128 x MIC. However, the ODs of biofilms after
      incubation with an antibiotic were significantly lower than the ODs of biofilms
      without antibiotic (P<0.05). A significant decrease in the biofilms with
      increasing antibiotic concentrations was observed for teicoplanin and
      moxifloxacin, but not for penicillin G. CONCLUSIONS: VGS isolated from patients
      with endocarditis and patients with sepsis and neutropenia form biofilms.
      Biofilms persist even when exposed to antibiotics at concentrations up to 128 x
      MIC. Nevertheless, teicoplanin and moxifloxacin reduced the density of the
      biofilms at concentrations >/=16 x MIC. Thus, testing the effects of antibiotics
      on biofilms may supply useful information in addition to standard in vitro
      testing, particularly in diseases where biofilm formation is involved in the
      pathogenesis.

PMID- 15563520
TI  - Functional analyses of tiptop and antennapedia in the embryonic development of
      Oncopeltus fasciatus suggests an evolutionary pathway from ground state to insect
      legs.
AB  - In insects, selector genes are thought to modify the development of a default, or
      'ground state', appendage into a tagma-specific appendage such as a mouthpart,
      antenna or leg. In the best described example, Drosophila melanogaster, the
      primary determination of leg identity is thought to result from regulatory
      interactions between the Hox genes and the antennal-specifying gene homothorax.
      Based on RNA-interference, a functional analysis of the selector gene tiptop and
      the Hox gene Antennapedia in Oncopeltus fasciatus embryogenesis is presented. It
      is shown that, in O. fasciatus, tiptop is required for the segmentation of distal
      leg segments and is required to specify the identity of the leg. The distal
      portions of legs with reduced tiptop develop like antennae. Thus, tiptop can act
      as a regulatory switch that chooses between antennal and leg identity. By
      contrast, Antennapedia does not act as a switch between leg and antennal
      identity. This observation suggests a significant difference in the mechanism of
      leg specification between O. fasciatus and D. melanogaster. These observations
      also suggest a significant plasticity in the mechanism of leg specification
      during insect evolution that is greater than would have been expected based on
      strictly morphological or molecular comparisons. Finally, it is proposed that a
      tiptop-like activity is a likely component of an ancestral leg specification
      mechanism. Incorporating a tiptop-like activity into a model of the leg
      specification mechanism explains several mutant phenotypes, previously described
      in D. melanogaster, and suggests a mechanism for the evolution of legs from a
      ground state.

PMID- 15563521
TI  - Evolutionary diversification of pigment pattern in Danio fishes: differential fms
      dependence and stripe loss in D. albolineatus.
AB  - The developmental bases for species differences in adult phenotypes remain
      largely unknown. An emerging system for studying such variation is the adult
      pigment pattern expressed by Danio fishes. These patterns result from several
      classes of pigment cells including black melanophores and yellow xanthophores,
      which differentiate during metamorphosis from latent stem cells of presumptive
      neural crest origin. In the zebrafish D. rerio, alternating light and dark
      horizontal stripes develop, in part, owing to interactions between melanophores
      and cells of the xanthophore lineage that depend on the fms receptor tyrosine
      kinase; zebrafish fms mutants lack xanthophores and have disrupted melanophore
      stripes. By contrast, the closely related species D. albolineatus exhibits a
      uniform pattern of melanophores, and previous interspecific complementation tests
      identified fms as a potential contributor to this difference between species.
      Here, we survey additional species and demonstrate marked variation in the fms
      dependence of hybrid pigment patterns, suggesting interspecific variation in the
      fms pathway or fms requirements during pigment pattern formation. We next examine
      the cellular bases for the evolutionary loss of stripes in D. albolineatus and
      test the simplest model to explain this transformation, a loss of fms activity in
      D. albolineatus relative to D. rerio. Within D. albolineatus, we demonstrate
      increased rates of melanophore death and decreased melanophore migration,
      different from wild-type D. rerio but similar to fms mutant D. rerio. Yet, we
      also find persistent fms expression in D. albolineatus and enhanced xanthophore
      development compared with wild-type D. rerio, and in stark contrast to fms mutant
      D. rerio. These findings exclude the simplest model in which stripe loss in D.
      albolineatus results from a loss of fms-dependent xanthophores and their
      interactions with melanophores. Rather, our results suggest an alternative model
      in which evolutionary changes in pigment cell interactions themselves have
      contributed to stripe loss, and we test this model by manipulating melanophore
      numbers in interspecific hybrids. Together, these data suggest evolutionary
      changes in the fms pathway or fms requirements, and identify changes in cellular
      interactions as a likely mechanism of evolutionary change in Danio pigment
      patterns.

PMID- 15563522
TI  - Microsurgical and laser ablation analysis of leaf positioning and dorsoventral
      patterning in tomato.
AB  - Leaves are arranged according to regular patterns, a phenomenon referred to as
      phyllotaxis. Important determinants of phyllotaxis are the divergence angle
      between successive leaves, and the size of the leaves relative to the shoot axis.
      Young leaf primordia are thought to provide positional information to the
      meristem, thereby influencing the positioning of new primordia and hence the
      divergence angle. On the contrary, the meristem signals to the primordia to
      establish their dorsoventral polarity, which is a prerequisite for the formation
      of a leaf blade. These concepts originate from classical microsurgical studies
      carried out between the 1920s and the 1970s. Even though these techniques have
      been abandoned in favor of genetic analysis, the resulting insights remain a
      cornerstone of plant developmental biology. Here, we employ new microsurgical
      techniques to reassess and extend the classical studies on phyllotaxis and leaf
      polarity. Previous experiments have indicated that the isolation of an incipient
      primordium by a tangential incision caused a change of divergence angle between
      the two subsequent primordia, indicating that pre-existing primordia influence
      further phyllotaxis. Here, we repeat these experiments and compare them with the
      results of laser ablation of incipient primordia. Furthermore, we explore to what
      extent the different pre-existing primordia influence the size and position of
      new organs, and hence phyllotaxis. We propose that the two youngest primordia (P1
      and P2) are sufficient for the approximate positioning of the incipient
      primordium (I1), and therefore for the perpetuation of the generative spiral,
      whereas the direct contact neighbours of I1 (P2 and P3) control its delimitation
      and hence its exact size and position. Finally, we report L1-specific cell
      ablation experiments suggesting that the meristem L1 layer is essential for the
      dorsoventral patterning of leaf primordia.

PMID- 15563523
TI  - Functions of heparan sulfate proteoglycans in cell signaling during development.
AB  - Heparan sulfate proteoglycans (HSPGs) are cell-surface and extracellular matrix
      macromolecules that are composed of a core protein decorated with covalently
      linked glycosaminoglycan (GAG) chains. In vitro studies have demonstrated the
      roles of these molecules in many cellular functions, and recent in vivo studies
      have begun to clarify their essential functions in development. In particular,
      HSPGs play crucial roles in regulating key developmental signaling pathways, such
      as the Wnt, Hedgehog, transforming growth factor-beta, and fibroblast growth
      factor pathways. This review highlights recent findings regarding the functions
      of HSPGs in these signaling pathways during development.

PMID- 15563524
TI  - The chianti zebrafish mutant provides a model for erythroid-specific disruption
      of transferrin receptor 1.
AB  - Iron is a crucial metal for normal development, being required for the production
      of heme, which is incorporated into cytochromes and hemoglobin. The zebrafish
      chianti (cia) mutant manifests a hypochromic, microcytic anemia after the onset
      of embryonic circulation, indicative of a perturbation in red blood cell
      hemoglobin production. We show that cia encodes tfr1a, which is specifically
      expressed in the developing blood and requisite only for iron uptake in erythroid
      precursors. In the process of isolating zebrafish tfr1, we discovered two tfr1
      like genes (tfr1a and tfr1b) and a single tfr2 ortholog. Abrogation of tfr1b
      function using antisense morpholinos revealed that this paralog was dispensable
      for hemoglobin production in red cells. tfr1b morphants exhibited growth
      retardation and brain necrosis, similar to the central nervous system defects
      observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non
      erythroid tissues for iron acquisition. Overexpression of mouse Tfr1, mouse Tfr2,
      and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing
      that each of these transferrin receptors are capable of supporting iron uptake
      for hemoglobin production in vivo. Taken together, these data show that zebrafish
      tfr1a and tfr1b share biochemical function but have restricted domains of tissue
      expression, and establish a genetic model to study the specific function of Tfr1
      in erythroid cells.

PMID- 15563525
TI  - Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation
      and intracellular Ca2+ overload.
AB  - We have shown that intermittent interruption of immediate reflow at reperfusion
      (i.e., postconditioning) reduces infarct size in in vivo models after ischemia.
      Cardioprotection of postconditioning has been associated with attenuation of
      neutrophil-related events. However, it is unknown whether postconditioning before
      reoxygenation after hypoxia in cultured cardiomyocytes in the absence of
      neutrophils confers protection. This study tested the hypothesis that prevention
      of cardiomyocyte damage by hypoxic postconditioning (Postcon) is associated with
      a reduction in the generation of reactive oxygen species (ROS) and intracellular
      Ca(2+) overload. Primary cultured neonatal rat cardiomyocytes were exposed to 3 h
      of hypoxia followed by 6 h of reoxygenation. Cardiomyocytes were postconditioned
      after the 3-h index hypoxia by three cycles of 5 min of reoxygenation and 5 min
      of rehypoxia applied before 6 h of reoxygenation. Relative to sham control and
      hypoxia alone, the generation of ROS (increased lucigenin-enhanced
      chemiluminescence, SOD-inhibitable cytochrome c reduction, and generation of
      hydrogen peroxide) was significantly augmented after immediate reoxygenation as
      was the production of malondialdehyde, a product of lipid peroxidation.
      Concomitant with these changes, intracellular and mitochondrial Ca(2+)
      concentrations, which were detected by fluorescent fluo-4 AM and X-rhod-1 AM
      staining, respectively, were elevated. Cell viability assessed by propidium
      iodide staining was decreased consistent with increased levels of lactate
      dehydrogenase after reoxygenation. Postcon treatment at the onset of
      reoxygenation reduced ROS generation and malondialdehyde concentration in media
      and attenuated cardiomyocyte death assessed by propidium iodide and lactate
      dehydrogenase. Postcon treatment was associated with a decrease in intracellular
      and mitochondrial Ca(2+) concentrations. These data suggest that Postcon
      treatment reduces reoxygenation-induced injury in cardiomyocytes and is
      potentially mediated by attenuation of ROS generation, lipid peroxidation, and
      intracellular and mitochondrial Ca(2+) overload.

PMID- 15563526
TI  - Myocardial hibernation: a delicate balance.
AB  - The pathophysiology of myocardial hibernation is characterized as a situation of
      reduced regional contractile function distal to a coronary artery stenosis that
      recovers after removal of the coronary stenosis. A subacute "downregulation" of
      contractile function in response to reduced regional myocardial blood flow
      exists, which normalizes regional energy and substrate metabolism but does not
      persist for more than 12-24 h. Chronic hibernation develops in response to one or
      more episodes of myocardial ischemia-reperfusion, possibly progressing from
      repetitive stunning with normal blood flow to hibernation with reduced blood
      flow. An upregulation of a protective gene program is seen in hibernating
      myocardium, putting it into the context of preconditioning. The morphology of
      hibernating myocardium is characterized by both adaptive and degenerative
      features.

PMID- 15563527
TI  - Sexual dimorphism in the permeability response of coronary microvessels to
      adenosine.
AB  - Gender influences volume regulation via several mechanisms; whether these include
      microvascular exchange, especially in the heart, is not known. In response to
      adenosine (Ado), permeability (P(s)) to protein of coronary arterioles of female
      pigs decreases acutely. Whether Ado induces similar P(s) changes in arterioles
      from males or whether equivalent responses occur in coronary venules of either
      sex has not been determined. Hypotheses that 1) basal P(s) properties and 2) P(s)
      responses to vasoactive stimuli are sex independent were evaluated from measures
      of P(s) to two hydrophilic proteins, alpha-lactalbumin and porcine serum albumin
      (PSA), in arterioles and venules isolated from hearts of adult male and female
      pigs. Consistent with hypothesis 1, basal P(s) values of both microvessel types
      were independent of sex. Contrary to hypothesis 2, P(s) responses to Ado varied
      with sex, protein, and vessel type. Confirming earlier studies, Ado induced a
      approximately 20% decrease in P(s) to both proteins in coronary arterioles from
      females. In arterioles from males, Ado did not change P(s) for alpha-lactalbumin
      (P(s)(alpha-lactalb), 3 +/- 13%), whereas P(s) for PSA (P(s)(PSA)) decreased by
      27 +/- 8% (P < 0.005). In venules from females, Ado elevated P(s)(PSA) by 44 +/-
      20% (P < 0.05), whereas in those from males, Ado reduced P(s)(PSA) by 24 +/- 5%
      (P < 0.05). The variety of outcomes is consistent with transvascular protein and
      protein-carried solute flux being regulated by multiple sex-dependent mechanisms
      in the heart and provides evidence of differences in exchange homeostasis of
      males and females in health and, likely, disease.

PMID- 15563528
TI  - Oxygen transport by low and normal oxygen affinity hemoglobin vesicles in extreme
      hemodilution.
AB  - The oxygen transport capacity of phospholipid vesicles encapsulating purified Hb
      (HbV) produced with a Po(2) at which Hb is 50% saturated (P 50 ) of 8 (HbV(8))
      and 29 mmHg (HbV(29)) was investigated in the hamster chamber window model by
      using microvascular measurements to determine oxygen delivery during extreme
      hemodilution. Two isovolemic hemodilution steps were performed with 5%
      recombinant albumin (rHSA) until Hct was 35% of baseline. Isovolemic exchange was
      continued using HbV suspended in rHSA solution to a total [Hb] of 5.7 g/dl in
      blood. P(50) was modified by coencapsulating pyridoxal 5'-phosphate. Final Hct
      was 11% for the HbV groups, with a plasma [Hb] of 2.1 +/- 0.1 g/dl after exchange
      with HbV(8) or HbV(29). A reference group was hemodiluted to Hct 11% with only
      rHSA. All groups showed stable blood pressure and heart rate. Arterial oxygen
      tensions were significantly higher than baseline for the HbV groups and the rHSA
      group and significantly lower for the HbV groups compared with the rHSA group.
      Blood pressure was significantly higher for the HbV(8) group compared with the
      HbV(29) group. Arteriolar and venular blood flows were significantly higher than
      baseline for the HbV groups. Microvascular oxygen delivery and extraction were
      similar for the HbV groups but lower for the rHSA group (P < 0.05). Venular and
      tissue Po(2) were statistically higher for the HbV(8) vs. the HbV(29) and rHSA
      groups (P < 0.05). Improved tissue Po(2) is obtained when red blood cells deliver
      oxygen in combination with a high- rather than low-affinity oxygen carrier.

PMID- 15563529
TI  - C-reactive protein does not relax vascular smooth muscle: effects mediated by
      sodium azide in commercially available preparations.
AB  - C-reactive protein (CRP), an acute-phase protein and newly recognized indicator
      of cardiovascular risk, may have direct actions on the vascular wall. Previous
      studies suggest that CRP is a vasodilator that activates smooth muscle K(+)
      channels. We examined the reported vasoactive properties of CRP and further
      explored its mechanisms of action. CRP decreased blood pressure in rats and
      increased coronary flow in open-chest dogs at a constant coronary perfusion
      pressure. CRP relaxed rat aortic rings and mesenteric small arteries that were
      contracted with phenylephrine. Relaxation was not affected by endothelial
      denudation or inhibition of nitric oxide (NO) synthase but was blocked by
      inhibition of soluble guanylate cyclase or K(+) channels. CRP solutions remained
      effective, i.e., elicited vasodilation, even after boiling or enzymatic
      digestion, which suggests the presence of a nonprotein contaminant. Sodium azide
      (NaN(3), 0.1%) is the preservative used for commercially available CRP and a
      potential source of NO. NaN(3) elicited the same cardiovascular effects as CRP
      preparations at equal concentrations, and its actions were blocked by inhibition
      of guanylate cyclase and K(+) channels. NaN(3)-free CRP, prepared by gel
      filtration centrifugation and confirmed by electrophoresis, had no effect on
      vascular tone. Inhibition of vascular smooth muscle catalase with 3-amino-1,2,4
      triazole completely prevented the effects of NaN(3) and NaN(3)-containing CRP
      solutions. We demonstrate that the acute vasoactive properties of commercially
      available CRP preparations are attributable to NaN(3) (and subsequent production
      of NO by catalase); therefore, this study suggests a reappraisal of the acute
      role of CRP in regulating vascular tone.

PMID- 15563530
TI  - Plasma ATP during exercise: possible role in regulation of coronary blood flow.
AB  - It was previously shown that red blood cells release ATP when blood oxygen
      tension decreases. ATP acts on microvascular endothelial cells to produce a
      retrograde conducted vasodilation (presumably via gap junctions) to the upstream
      arteriole. These observations form the basis for an ATP hypothesis of local
      metabolic control of coronary blood flow due to vasodilation in microvascular
      units where myocardial oxygen extraction is high. Dogs (n = 10) were instrumented
      with catheters in the aorta and coronary sinus, and a flow transducer was placed
      around the circumflex coronary artery. Arterial and coronary venous plasma ATP
      concentrations were measured at rest and during three levels of treadmill
      exercise by using a luciferin-luciferase assay. During exercise, myocardial
      oxygen consumption increased approximately 3.2-fold, coronary blood flow
      increased approximately 2.7-fold, and coronary venous oxygen tension decreased
      from 19 to 12.9 mmHg. Coronary venous plasma ATP concentration increased
      significantly from 31.1 to 51.2 nM (P < 0.01) during exercise. Coronary blood
      flow increased linearly with coronary venous ATP concentration (P < 0.01).
      Coronary venous-arterial plasma ATP concentration difference increased
      significantly during exercise (P < 0.05). The data support the hypothesis that
      ATP is one of the factors controlling coronary blood flow during exercise.

PMID- 15563531
TI  - Rosuvastatin reduces experimental left ventricular infarct size after ischemia
      reperfusion injury but not total coronary occlusion.
AB  - This study compared the effects of rosuvastatin on left ventricular infarct size
      in mice after permanent coronary occlusion vs. 60 min of ischemia followed by 24
      h of reperfusion. Statins can inhibit neutrophil adhesion, increase nitric oxide
      synthase (NOS) expression, and mobilize progenitor stem cells after ischemic
      injury. Mice received blinded and randomized administration of rosuvastatin (20
      mg.kg(-1).day(-1)) or saline from 2 days before surgery until death. After 60 min
      of ischemia with reperfusion, infarct size was reduced by 18% (P = 0.03) in mice
      randomized to receive rosuvastatin (n = 18) vs. saline (n = 22) but was similar
      after permanent occlusion in rosuvastatin (n = 17) and saline (n = 20) groups (P
      = not significant). Myocardial infarct size after permanent left anterior
      descending coronary artery occlusion (n = 6) tended to be greater in NOS3
      deficient mice than in the wild-type saline group (33 +/- 4 vs. 23 +/- 2%, P =
      0.08). Infarct size in NOS3-deficient mice was not modified by treatment with
      rosuvastatin (34 +/- 5%, n = 6, P = not significant vs. NOS3-deficient saline
      group). After 60 min of ischemia-reperfusion, neutrophil infiltration was similar
      in rosuvastatin and saline groups as was the percentage of CD34(+), Sca-1(+), and
      c-Kit(+) cells. Left ventricular NOS3 mRNA and protein levels were unchanged by
      rosuvastatin. Rosuvastatin reduces infarct size after 60 min of ischemia
      reperfusion but not after permanent coronary occlusion, suggesting a potential
      anti-inflammatory effect. Although we were unable to demonstrate that the
      myocardial protection was due to an effect on neutrophil infiltration, stem cell
      mobilization, or induction of NOS3, these data suggest that rosuvastatin may be
      particularly beneficial in myocardial protection after ischemia-reperfusion
      injury.

PMID- 15563532
TI  - Microvascular oxygen delivery and consumption following treatment with verapamil.
AB  - The microvascular distribution of oxygen was studied in the arterioles and
      venules of the awake hamster window chamber preparation to determine the
      contribution of vascular smooth muscle relaxation to oxygen consumption of the
      microvascular wall during verapamil-induced vasodilatation. Verapamil HCl
      delivered in a 0.1 mg/kg bolus injection followed by a continuous infusion of
      0.01 mg.kg(-1).min(-1) caused significant arteriolar dilatation, increased
      microvascular flow and functional capillary density, and decreased arteriolar
      vessel wall transmural Po(2) difference. Verapamil caused tissue Po(2) to
      increase from 25.5 +/- 4.1 mmHg under control condition to 32.0 +/- 3.7 mmHg
      during verapamil treatment. Total oxygen released by the microcirculation to the
      tissue remained the same as at baseline. Maintenance of the same level of oxygen
      release to the tissue, increased tissue Po(2), and decreased wall oxygen
      concentration gradient are compatible if vasodilatation significantly lowers
      vessel wall oxygen consumption, which in this model appears to constitute an
      important oxygen-consuming compartment. These findings show that treatment with
      verapamil, which increases oxygen supply through vasodilatation, may further
      improve tissue oxygenation by lowering oxygen consumption of the
      microcirculation.

PMID- 15563533
TI  - Endogenous endothelin attenuates the pressor response to acute environmental
      stress via the ETA receptor.
AB  - Clinical studies have documented an abrupt rise in plasma endothelin-1 (ET-1)
      coincident with an increase in mean arterial pressure (MAP) during the response
      to acute stress. We therefore examined the ET(A) and ET(B) receptor-dependent
      effects of ET-1 on the pressor response to acute environmental stress in ET-1
      dependent hypertension. Stress was induced by administration of air jet pulses (3
      min) in ET(B) receptor-deficient (ET(B) sl/sl) rats fed normal salt (NS; 0.8%
      NaCl), high salt (HS; 8% NaCl), and HS plus the ET(A) receptor antagonist ABT-627
      (5 mg.kg(-1).day(-1)) on successive weeks. MAP was chronically monitored by
      telemetry. Total pressor response (area under the curve) was significantly
      reduced in ET(B) sl/sl rats maintained on a HS vs. NS diet [-6.8 mmHg (SD 18.7)
      vs. 29.3 mmHg (SD 8.1) x 3 min, P < 0.05]. Conversely, the total pressor response
      was augmented in both wild-type [34.2 mmHg (SD 29.2) x 3 min, P < 0.05 vs. NS]
      and ET(B) sl/sl rats [49.1 mmHg (SD 11.8) x 3 min, P < 0.05 vs. NS] by ABT-627.
      Blockade of ET(B) receptors in Sprague-Dawley rats caused an increase in basal
      MAP that was enhanced by HS and lowered by mixed ET(A)/ET(B) receptor antagonism;
      none of these treatments, however, had any effect on the pressor response. These
      data demonstrate that increasing endogenous ET-1 suppresses the pressor response
      to acute stress through ET(A) receptor activation in a genetic model of ET-1
      dependent hypertension. These results are consistent with reports that ET-1 can
      attenuate sympathetically mediated responses.

PMID- 15563534
TI  - Compensatory mechanisms influence hemostasis in setting of eNOS deficiency.
AB  - The balance between thrombosis and hemorrhage is carefully regulated. Nitric
      oxide (NO) is an important mediator of these processes, as it prevents platelet
      adhesion to the endothelium and inhibits platelet recruitment. Although
      endothelial NO synthase (eNOS)-deficient mice have decreased vascular reactivity
      and mild hypertension, enhanced thrombosis in vivo has not been demonstrated. To
      determine the role of endogenous NO in hemostasis, a model of carotid arterial
      injury and thrombosis was performed using eNOS-deficient and wild-type mice.
      Paradoxically, the eNOS-deficient animals had a prolongation of time to occlusion
      compared with the wild-type mice (P < 0.001). Consistent with this finding,
      plasma markers suggesting enhanced fibrinolysis [tissue plasminogen activator (t
      PA) activity and antigen and D-dimer levels] were significantly elevated in eNOS
      deficient animals. Vascular tissue expression of t-PA and platelet activity
      levels were not altered. In endothelial cells, t-PA is stored in Weibel-Palade
      bodies, and exocytosis of these storage granules is inhibited by NO. Thus in the
      absence of NO, release of Weibel-Palade body contents (and t-PA) could be
      enhanced; this observation is also supported by increased von Willebrand factor
      levels observed in eNOS-deficient animals. In summary, although eNOS deficiency
      attenuates vascular reactivity and increases platelet recruitment, it is also
      associated with enhanced fibrinolysis due to lack of NO-dependent inhibition of
      Weibel-Palade body release. These processes highlight the complexity of NO
      dependent regulation of vascular homeostasis. Such compensatory mechanisms may
      partially explain the lack of spontaneous thrombosis, minimally elevated baseline
      blood pressure, and normal life span that are seen in animals deficient in a
      pivotal regulator of vascular patency.

PMID- 15563535
TI  - Heart rate recovery after exercise: a predictor of ventricular fibrillation
      susceptibility after myocardial infarction.
AB  - Heart rate recovery after exercise, thought to be related to cardiac
      parasympathetic tone, has been shown to be a prognostic tool for all-cause
      mortality. However, the relationship between this variable and confirmed
      susceptibility to ventricular fibrillation (VF) has not been established.
      Therefore, myocardial ischemia was induced with a 2-min occlusion of the left
      circumflex artery during the last minute of exercise in mongrel dogs with
      myocardial infarction (n = 105 dogs). VF was induced in 66 animals (susceptible),
      whereas the remaining 39 dogs had no arrhythmias (resistant). On a previous day,
      ECG was recorded and a time-series analysis of heart rate variability was
      measured 30, 60, and 120 s after submaximal exercise (treadmill running). The
      heart rate recovery was significantly greater in resistant dogs than in
      susceptible dogs at all three times, with the most dramatic difference at the 30
      s mark (change from maximum: 48.1 +/- 3.6 beats/min, resistant dogs; 31.0 +/- 2.2
      beats/min, susceptible dogs). Correspondingly, indexes of parasympathetic tone
      increased to a significantly greater extent in resistant dogs at 30 and 60 s
      after exercise. These differences were eliminated by atropine pretreatment. When
      considered together, these data suggest that resistant animals exhibit a more
      rapid recovery of vagal activity after exercise than those susceptible to VF. As
      such, postexercise heart rate recovery may help identify patients with a high
      risk for VF following myocardial infarction.

PMID- 15563536
TI  - VR-1 receptor blockade attenuates the pressor response to capsaicin but has no
      effect on the pressor response to contraction in cats.
AB  - Vanilloid type 1 (VR-1) receptors are stimulated by capsaicin and hydrogen ions,
      the latter being a by-product of muscular contraction. We tested the hypothesis
      that activation of VR-1 receptors during static contraction contributes to the
      exercise pressor reflex. We established a dose of iodoresinaferatoxin (IRTX), a
      VR-1 receptor antagonist, that blocked the pressor response to capsaicin injected
      into the arterial supply of muscle. Specifically, in eight decerebrated cats, we
      compared pressor responses to capsaicin (10 mug) injected into the right
      popliteal artery, which was subsequently injected with IRTX (100 mug), with those
      to capsaicin injected into the left popliteal artery, which was not injected with
      IRTX. The pressor response to capsaicin injected into the right popliteal artery
      averaged 49 +/- 9 mmHg before IRTX and 9 +/- 2 mmHg after IRTX (P < 0.05). In
      contrast, the pressor response to capsaicin injected into the left popliteal
      artery averaged 46 +/- 10 mmHg "before" and 43 +/- 6 mmHg "after" (P > 0.05). We
      next determined whether VR-1 receptors mediated the pressor response to
      contraction of the triceps surae. During contraction without circulatory
      occlusion, the pressor response before IRTX (100 mug) averaged 26 +/- 3 mmHg,
      whereas it averaged 22 +/- 3 mmHg (P > 0.05) after IRTX (n = 8). In addition,
      during contraction with occlusion, the pressor responses averaged 35 +/- 3 mmHg
      before IRTX injection and 49 +/- 7 mmHg after IRTX injection (n = 7). We conclude
      that VR-1 receptors play little role in evoking the exercise pressor reflex.

PMID- 15563537
TI  - Mitochondrial membrane potential modulates regulation of mitochondrial Ca2+ in
      rat ventricular myocytes.
AB  - Although recent studies focused on the contribution of mitochondrial Ca2+ to the
      mechanisms of ischemia-reperfusion injury, the regulation of mitochondrial Ca2+
      under pathophysiological conditions remains largely unclear. By using saponin
      permeabilized rat myocytes, we measured mitochondrial membrane potential
      (DeltaPsi(m)) and mitochondrial Ca2+ concentration ([Ca2+](m)) at the
      physiological range of cytosolic Ca2+ concentration ([Ca2+](c); 300 nM) and
      investigated the regulation of [Ca2+](m) during both normal and dissipated
      DeltaPsi(m). When DeltaPsi(m) was partially depolarized by carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP, 0.01-0.1 microM), there were dose
      dependent decreases in [Ca2+](m). When complete DeltaPsi(m) dissipation was
      achieved by FCCP (0.3-1 microM), [Ca2+](m) remained at one-half of the control
      level despite no Ca2+ influx via the Ca2+ uniporter. The DeltaPsi(m) dissipation
      by FCCP accelerated calcein leakage from mitochondria in a cyclosporin A (CsA)
      sensitive manner, which indicates that DeltaPsi(m) dissipation opened the
      mitochondrial permeability transition pore (mPTP). After FCCP addition,
      inhibition of the mPTP by CsA caused further [Ca2+](m) reduction; however,
      inhibition of mitochondrial Na+/Ca2+ exchange (mitoNCX) by a Na+-free solution
      abolished this [Ca2+](m) reduction. Cytosolic Na(+) concentrations that yielded
      one-half maximal activity levels for mitoNCX were 3.6 mM at normal DeltaPsi(m)
      and 7.6 mM at DeltaPsi(m) dissipation. We conclude that 1) the mitochondrial Ca2+
      uniporter accumulates Ca2+ in a manner that is dependent on DeltaPsi(m) at the
      physiological range of [Ca2+](c); 2) DeltaPsi(m) dissipation opens the mPTP and
      results in Ca2+ influx to mitochondria; and 3) although mitoNCX activity is
      impaired, mitoNCX extrudes Ca2+ from the matrix even after DeltaPsi(m)
      dissipation.

PMID- 15563538
TI  - Early vasodilator response to anodal current application in human is not impaired
      by cyclooxygenase-2 blockade.
AB  - It is generally acknowledged that cutaneous vasodilatation in response to
      monopolar galvanic current application would result from an axon reflex in
      primary afferent fibers and the neurogenic inflammation resulting from
      neuropeptide release. Previous studies suggested participation of prostaglandin
      (PG) in anodal current-induced cutaneous vasodilatation. Thus the inducible
      cyclooxygenase (COX) isoform (COX-2), assumed to play a key role in inflammation,
      should be involved in the synthesis of the PG that is released. Skin blood flow
      (SkBF) variations induced by 5 min of 0.1-mA monopolar anodal current application
      were evaluated with laser-Doppler flowmetry on the forearm of healthy volunteers
      treated with indomethacin (COX-1 and COX-2 inhibitor), celecoxib (COX-2
      inhibitor), or placebo. SkBF was indexed as cutaneous vascular conductance (CVC),
      expressed as percentage of heat-induced maximal CVC (%MVC). Urinalyses were
      performed to test celecoxib treatment efficiency. No difference was found in CVC
      values at rest: 14.3 +/- 4.0, 11.9 +/- 3.2, and 10.9 +/- 2.0% MVC after
      indomethacin, celecoxib, and placebo treatment, respectively. At 10 min after the
      onset of anodal current application, CVC values were 22.2 +/- 4.9% MVC (not
      significantly different from rest) with indomethacin, 85.7 +/- 15.3% MVC (P <
      0.001 vs. rest) with celecoxib, and 70.4 +/- 13.1% MVC (P < 0.001 vs. rest) with
      placebo. Celecoxib significantly depressed the urinary prostacyclin metabolite 6
      keto-PGF(1alpha) (P < 0.05 vs. placebo). Indomethacin, but not celecoxib,
      significantly inhibited the anodal current-induced vasodilatation. Thus, although
      they are assumed to result from an axon reflex in primary afferent fibers and
      neurogenic inflammation, these results suggest that the early anodal current
      induced vasodilatation is mainly dependent on COX-1-induced PG synthesis.

PMID- 15563539
TI  - Sodium channel enhancer restores baroreflex sensitivity in conscious dogs with
      heart failure.
AB  - We compared the cardiac inotropic, lusitropic, and chronotropic responses to the
      Na(+) channel enhancer LY-368052 in conscious dogs before and after development
      of congestive heart failure (CHF). We also examined the effect of LY-368052 on
      baroreflex sensitivity and the efferent neural mechanisms of the bradycardic
      response in heart failure. Dogs were chronically instrumented, and heart failure
      was induced by right ventricular pacing at 240 beats/min for 3-4 wk. LY-368052
      dose-dependently increased left ventricular contractile performance before and
      after the development of CHF to a similar extent. The inotropic effect of LY
      368052 in heart failure was not altered by either ganglionic or beta-adrenergic
      receptor blockade. LY-368052 improved cardiac relaxation and induced bradycardia
      in dogs with heart failure but not in normal dogs. The negative chronotropic
      effect of LY-368052 was eliminated by ganglionic blockade but not beta-adrenergic
      blockade, suggesting that the bradycardia was mediated by the autonomic nervous
      system via enhanced parasympathetic tone. Baroreflex sensitivity was assessed as
      the pulse interval-mean arterial pressure slope in response to temporary
      pharmacological (nitroglycerin or phenylephrine) and mechanical (brief occlusion
      of inferior vena cava) alterations of arterial pressure in conscious dogs before
      and after development of heart failure. Baroreflex sensitivity was significantly
      depressed in heart failure and restored completely by acute treatment with LY
      368052. Thus the Na(+) channel enhancer LY-368052 maintains its beta-receptor
      independent inotropic effect in chronic CHF and specifically improves ventricular
      relaxation and depressed baroreflex function.

PMID- 15563540
TI  - Met5-enkephalin-induced cardioprotection occurs via transactivation of EGFR and
      activation of PI3K.
AB  - Our previous studies indicated that opioid-induced cardioprotection occurs via
      activation of mitochondrial ATP-sensitive K(+) (K(ATP)) channels. However, other
      elements of the Met(5)-enkephalin (ME) cardioprotection pathway are not fully
      characterized. In the present study, we investigated the role of tyrosine kinase,
      MAPK, and phosphatidylinositol 3-kinase (PI3K) signaling in ME-induced
      protection. Ca(2+)-tolerant, adult rabbit cardiomyocytes were isolated by
      collagenase digestion and subjected to simulated ischemia for 180 min. ME was
      administered 15 min before the 180 min of simulated ischemia; blockers were
      administered 15 min before ME. Cell death was assessed by trypan blue as a
      function of time. The epidermal growth factor receptor (EGFR) kinase inhibitor AG
      1478 (250 nM) blocked ME-induced protection, but the inactive analog AG-9 (100
      microM) did not. Treatment with herbimycin (1 microM) completely eliminated ME
      induced protection. To verify that ME activates EGFR and to determine the
      involvement of Src, Western blotting of EGFR was performed after ME
      administration with and without herbimycin A. ME resulted in herbimycin-sensitive
      robust phosphorylation of EGFR at Tyr(992) and Tyr(1068). Administration of the
      selective MAPK inhibitor PD-98059 (10 nM) and the specific MEK1/2 inhibitor U
      0126 (10 microM) also inhibited ME-induced cardioprotection. ME-induced ERK1/2
      phosphorylation was significantly reduced by PD-98059, the EGFR kinase inhibitor
      PD-153035 (10 microM), and chelerythrine (2 microM). The PI3K inhibitor LY-294002
      (20 microM) abrogated ME-induced protection, and ME-induced Akt phosphorylation
      at Ser(473) was suppressed by LY-294002, PD-153035, and chelerythrine. We
      conclude that ME-induced cardioprotection is mediated via Src-dependent EGFR
      transactivation and activation of the PI3K and MAPK pathways.

PMID- 15563541
TI  - Assessment of left ventricular diastolic suction in dogs using wave-intensity
      analysis.
AB  - Two apparently different types of mechanisms have emerged to explain diastolic
      suction (DS), that property of the left ventricle (LV) that tends to cause it to
      refill itself during early diastole independent of any force from the left atrium
      (LA). By means of the first mechanism, DS depends on decreased elastance [e.g.,
      the relaxation time constant (tau)] and, by the second, end-systolic volume
      (V(LVES)). We used wave-intensity analysis (WIA) to measure the total energy
      transported by the backward expansion wave (I(W-)) during LV relaxation in an
      attempt to reconcile these mechanisms. In six anesthetized, open-chest dogs, we
      measured aortic, LV (P(LV)), LA (P(LA)), and pericardial pressures and LV volume
      by orthogonal ultrasonic crystals. Mitral velocity was measured by Doppler
      echocardiography, and aortic velocity was measured by an ultrasonic flow probe.
      Heart rate was controlled by pacing, V(LVES) by volume loading, and tau by
      isoproterenol or esmolol administration. I(W-) was found to be inversely related
      to tau and V(LVES). Our measure of DS, the energy remaining after mitral valve
      opening, I(W-DS), was also found to be inversely related to tau and V(LVES) and
      was approximately 10% of the total "aspirating" energy generated by LV relaxation
      (i.e., I(W-)). The size of the Doppler (early filling) E wave depended on I(W-DS)
      in addition to I(W+), the energy associated with LA decompression. We conclude
      that the energy of the backward-going wave generated by the LV during relaxation
      depends on both the rate at which elastance decreases (i.e., tau) and V(LVES).
      WIA provides a new approach for assessing DS and reconciles those two previously
      proposed mechanisms. The E wave depends on DS in addition to LA decompression.

PMID- 15563542
TI  - Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in
      phospholemman-deficient mice.
AB  - Phospholemman (FXYD1), a 72-amino acid transmembrane protein abundantly expressed
      in the heart and skeletal muscle, is a major substrate for phosphorylation in the
      cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies
      have suggested a number of possible roles for this protein, including ion channel
      modulator, taurine-release channel, Na(+)/Ca(2+) exchanger modulator, and Na-K
      ATPase-associated subunit. We have generated a phospholemman-deficient mouse. The
      adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and
      ejection fractions that were 9% higher by magnetic resonance imaging compared
      with wild-type animals. Notably, this occurred in the absence of hypertension.
      Total Na-K-ATPase activity was 50% lower in the phospholemman-deficient hearts.
      Expression (per unit of membrane protein) of total Na-K-ATPase was only slightly
      diminished, but expression of the minor alpha(2)-isoform, which has been
      specifically implicated in the control of contractility, was reduced by 60%. The
      absence of phospholemman thus results in a complex response, including a
      surprisingly large reduction in intrinsic Na-K-ATPase activity, changes in Na-K
      ATPase isoform expression, increase in ejection fraction, and increase in cardiac
      mass. We hypothesize that a primary effect of phospholemman is to modulate the Na
      K-ATPase and that its reduced activity initiates compensatory responses.

PMID- 15563543
TI  - Sarcolemmal KATP channel triggers delayed ischemic preconditioning in rats.
AB  - Previous work from our laboratory has shown that the sarcolemmal K(ATP) channel
      (sK(ATP)) is required as a trigger for delayed cardioprotection upon exogenous
      opioid administration. We also established that the mitochondrial K(ATP)
      (mK(ATP)) channel is not required for triggering delayed delta-opioid-induced
      infarct size reduction. Because mechanistic differences have been found among
      delta-opioids and that due to ischemic preconditioning (IPC), we determined
      whether the triggering mechanism of delayed IPC-induced infarct size reduction
      involves either the sK(ATP) or mK(ATP). Male Sprague-Dawley rats received either
      sham surgery or IPC (3- to 5-min cycles of ischemia and reperfusion) 24 h before
      being subjected to 30 min of ischemia and 2 h of reperfusion. Infarct size was
      determined and expressed as a percentage of the area at risk, with significance
      compared with sham reported at P </= 0.001. A subset of both sham and IPC-treated
      rats received either the selective sK(ATP) channel antagonist, HMR-1098 (6
      mg/kg), or the selective mK(ATP) channel antagonist, 5-hydroxydeconoic acid (5
      HD; 10 mg/kg), given 5 min before IPC. Rats subjected to IPC demonstrated a
      significant reduction in infarct size compared with sham (29.2 +/- 4.7 vs. 59.3
      +/- 2.5%, respectively; P </= 0.001). Prior administration of HMR-1098, but not 5
      HD, abolished IPC-induced infarct size reduction (48.8 +/- 2.9 and 28.8 +/- 4.0%,
      respectively; P </= 0.001). Furthermore, administration of HMR 24 h after IPC,
      before index ischemia, did not abrogate IPC-induced infarct size reduction (33.0
      +/- 5.0 vs. 29.2 +/- 4.7%, respectively; P </= 0.001). These data suggest that
      the sK(ATP) channel is required as a trigger but not a mediator for delayed IPC
      induced infarct size reduction in rat hearts.

PMID- 15563544
TI  - Progesterone-independent effects of human progesterone receptors (PRs) in
      estrogen receptor-positive breast cancer: PR isoform-specific gene regulation and
      tumor biology.
AB  - Progesterone receptors (PRs) are prognostic markers in breast cancers
      irrespective of the patient's progestational status. However, there are two PR
      isoforms, PR-A and PR-B, that are equimolar in the normal breast but dysregulated
      in advanced disease. Postmenopausal, tamoxifen-treated patients with estrogen
      receptor (ER)-positive, PR-A-rich tumors have much faster disease recurrence than
      patients with PR-B-rich tumors. To study the mechanisms we engineered ER+ breast
      cancer cells that express each PR isoform under control of an inducible promoter.
      We identified 79 genes regulated by progesterone (P), mainly by PR-B, and 51
      genes regulated without progesterone, mainly by PR-A. Only nine genes were
      regulated with and without ligand, leading to definition of three classes: I)
      genes regulated only by liganded PR; II) genes regulated only by unliganded PR;
      III) genes regulated by both. Unliganded PR-A and PR-B differentially regulate
      genes that coordinate extracellular signaling pathways and influence tumor cell
      biology. Indeed, in the absence of P, compared with ER+/PR-B+ or PR- cells, ER+,
      PR-A+ cells exhibit an aggressive phenotype, are more adhesive to an
      extracellular matrix, and are more migratory. Additionally, unliganded PR-A and
      PR-B both inhibit cell growth and provoke resistance to Taxol-induced apoptosis.
      We propose that PR-A:PR-B ratios, even in the absence of P, influence the biology
      and treatment response of ER+ tumors, that PR-A isoforms are functionally
      dominant in P-deficient states, and that PR-A rich tumors are especially
      aggressive.

PMID- 15563545
TI  - Induction and regulation of Fas-mediated apoptosis in human thyroid epithelial
      cells.
AB  - Fas-mediated apoptosis has been proposed to play an important role in the
      pathogenesis of Hashimoto's thyroiditis. Normal thyroid cells are resistant to
      Fas-mediated apoptosis in vitro but can be sensitized by the unique combination
      of interferon-gamma and IL-1beta cytokines. We sought to examine the mechanism of
      this sensitization and apoptosis signaling in primary human thyroid cells.
      Without the addition of cytokines, agonist anti-Fas antibody treatment of the
      thyroid cells resulted in the cleavage of proximal caspases, but this did not
      lead to the activation of caspase 7 and caspase 3. Apoptosis associated with the
      cleavage of caspases 7, 3, and Bid, and the activation of mitochondria in
      response to anti-Fas antibody occurred only after cytokine pretreatment. Cell
      surface expression of Fas, the cytoplasmic concentrations of procaspases 7, 8,
      and 10, and the proapoptotic molecule Bid were markedly enhanced by the presence
      of the cytokines. In contrast, P44/p42 MAPK (Erk) appeared to provide protection
      from Fas-mediated apoptosis because an MAPK kinase inhibitor (U0126) sensitized
      thyroid cells to anti-Fas antibody. In conclusion, Fas signaling is blocked in
      normal thyroid cells at a point after the activation of proximal caspases.
      Interferon-gamma/IL-1beta pretreatment sensitizes human thyroid cells to Fas
      mediated apoptosis in a complex manner that overcomes this blockade through
      increased expression of cell surface Fas receptor, increases in proapoptotic
      molecules that result in mitochondrial activation, and late caspase cleavage.
      This process involves Bcl-2 family proteins and appears to be compatible with
      type II apoptosis regulation.

PMID- 15563546
TI  - Membrane-proximal region of the carboxyl terminus of the gonadotropin-releasing
      hormone receptor (GnRHR) confers differential signal transduction between
      mammalian and nonmammalian GnRHRs.
AB  - Recently, we demonstrated that the mammalian type-I GnRH receptor (GnRHR) has a
      high preference for the phospholipase C/protein kinase C (PLC/PKC)-linked
      signaling pathway, whereas non-mammalian bullfrog (bf) GnRHRs couple to both
      adenylate cyclase/protein kinase A (AC/PKA)- and PLC/PKC-linked signaling
      pathways. In the pre-sent study, using AC/PKA-specific reporter (cAMP-responsive
      element-luciferase) and PLC/PKC-specific reporter (serum-responsive element
      luciferase) systems, we attempted to identify the motif responsible for this
      difference. A deletion of the intracellular carboxyl-terminal tail (C tail) of
      bfGnRHR-1 remarkably decreased its ability to induce the AC/PKA-linked signaling
      pathway. Further dissection of the C tail indicated that an HFRK motif in the
      membrane-proximal sequence of bfGnRHR-1 C tail is a minimal requirement for the
      AC/PKA-linked signaling pathway as the addition of this motif to rat GnRHR or
      deletion of it from bfGnRHR-1 significantly affected the ability to induce the
      AC/PKA-linked signaling pathway. Deletion or addition of the HFRK motif, however,
      did not critically influence the PLC/PKC-linked signaling pathway. These results
      indicate that the HFRK motif in the membrane-proximal region confers the
      differential signal transduction pathways between mammalian and nonmammalian
      GnRHRs.

PMID- 15563547
TI  - Prediction of nuclear hormone receptor response elements.
AB  - The nuclear receptor (NR) class of transcription factors controls critical
      regulatory events in key developmental processes, homeostasis maintenance, and
      medically important diseases and conditions. Identification of the members of a
      regulon controlled by a NR could provide an accelerated understanding of
      development and disease. New bioinformatics methods for the analysis of
      regulatory sequences are required to address the complex properties associated
      with known regulatory elements targeted by the receptors because the standard
      methods for binding site prediction fail to reflect the diverse target site
      configurations. We have constructed a flexible Hidden Markov Model framework
      capable of predicting NHR binding sites. The model allows for variable spacing
      and orientation of half-sites. In a genome-scale analysis enabled by the model,
      we show that NRs in Fugu rubripes have a significant cross-regulatory potential.
      The model is implemented in a web interface, freely available for academic
      researchers, available at http://mordor.cgb.ki.se/NHR-scan.

PMID- 15563548
TI  - Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic
      changes that partially overlap with growth hormone-dependent effects.
AB  - Suppressor of cytokine signaling-2 (SOCS2)-deficient (SOCS2-/-) mice grow
      significantly larger than their littermates, suggesting that SOCS2 is important
      in the negative regulation of the actions of GH and/or IGF-I. The aim of this
      study was to identify genes and metabolic parameters that might contribute to the
      SOCS2-/- phenotype. We demonstrate that although SOCS2 deficiency induces
      significant changes in hepatic gene expression, only a fraction of these overlap
      with known GH-induced effects in the liver, suggesting that SOCS2 might be an
      important regulator of other growth factors and cytokines acting on the liver.
      However, an important role of GH and IGF-I in the phenotype of these animals was
      demonstrated by an overexpression of IGF-binding protein-3 mRNA in the liver and
      increased levels of circulating IGF-binding protein-3. Other GH-like effects
      included diminished serum triglycerides and down-regulation of lipoprotein lipase
      in adipose tissue. Interestingly, SOCS2-/- mice did not differ from their wild
      type littermates in glucose or insulin tolerance tests, which is in contrast with
      the known diabetogenic effects of GH. Furthermore, there was no evidence of
      impaired insulin signaling in primary hepatocytes isolated from SOCS2-/- mice.
      Moreover, increased expression of peroxisome proliferator-activated receptor
      gamma coactivator-1alpha mRNA was detected in skeletal muscle, which might
      contribute to normal glycemic control despite the apparent overactivity of the
      GH/IGF-I axis. Our data indicate that SOCS2 deficiency partially mimics a state
      of increased GH activity, but also results in changes that cannot be related to
      known GH effects.

PMID- 15563549
TI  - Propofol-block of SK channels in reticular thalamic neurons enhances GABAergic
      inhibition in relay neurons.
AB  - The GABAergic reticular thalamic nucleus (RTN) is a major source of inhibition
      for thalamocortical neurons in the ventrobasal complex (VB). Thalamic circuits
      are thought to be an important anatomic target for general anesthetics. We
      investigated presynaptic actions of the intravenous anesthetic propofol in RTN
      neurons, using RTN-retained and RTN-removed brain slices. In RTN-retained slices,
      focal and bath application of propofol increased intrinsic excitability, temporal
      summation, and spike firing rate in RTN neurons. Propofol-induced activation was
      associated with suppression of medium afterhyperpolarization potentials. This
      activation was mimicked and completely occluded by the small conductance calcium
      activated potassium (SK) channel blocker apamin, indicating that propofol could
      enhance RTN excitability by blocking SK channels. Propofol increased GABAergic
      transmission at RTN-VB synapses, consistent with excitation of presynaptic RTN
      neurons. Stimulation of RTN resulted in synaptic inhibition in postsynaptic
      neurons in VB, and this inhibition was potentiated by propofol in a concentration
      dependent manner. Removal of RTN resulted in a dramatic reduction of both
      spontaneous postsynaptic inhibitory current frequency and propofol-mediated
      inhibition of VB neurons. Thus the existence and activation of RTN input were
      essential for propofol to elicit thalamocortical suppression; such suppression
      resulted from shunting through the postsynaptic GABA(A) receptor-mediated
      chloride conductance. The results indicate that propofol enhancement of RTN
      mediated inhibitory input via blockade of SK channels may play a critical role in
      "gating" spike firing in thalamocortical relay neurons.

PMID- 15563550
TI  - Changes in the inhibitory control exerted by the antagonist Ia afferents on human
      wrist extensor motor units during an attention-demanding motor task.
AB  - The aim of this study was to determine the extent to which an attention-demanding
      visuomotor task affects the strength of the inhibitory control exerted by the
      wrist flexor group Ia afferents on the wrist extensor motoneurons. Effects of
      median nerve stimulation on the tonic activity of wrist extensor single motor
      units were analyzed in terms of the interspike interval (ISI) lengthening.
      Results show that the inhibitory effects exerted by the antagonistic group Ia
      afferents were significantly enhanced when the wrist extensor motoneurons were
      involved in an attention-demanding task. Enhanced inhibition from antagonist
      afferents may reflect task-related changes in the excitability of the di- and/or
      polysynaptic pathways mediating reciprocal inhibition due to either the action of
      descending inputs and/or an increase in the efficiency of the Ia inputs to the
      premotoneuronal inhibitory interneurons. Modulation of the inhibition exerted by
      proprioceptive antagonist afferents may be one of the processes which contribute
      to the fine adjustment of the wrist muscle force output required in fine handling
      tasks.

PMID- 15563551
TI  - Heat stress-mediated plasticity in a locust looming-sensitive visual interneuron.
AB  - Neural circuits are strongly affected by temperature and failure ensues at
      extremes. However, detrimental effects of high temperature on neural pathways can
      be mitigated by prior exposure to high, but sublethal temperatures (heat shock).
      Using the migratory locust, Locusta migratoria, we investigated the effects of
      heat shock on the thermosensitivity of a visual interneuron [the descending
      contralateral movement detector (DCMD)]. Activity in the DCMD was elicited using
      a looming stimulus and the response was recorded from the axon using
      intracellular and extracellular methods. The thoracic region was perfused with
      temperature-controlled saline and measurements were taken at 5 degrees intervals
      starting at 25 degrees C. Activity in DCMD was decreased in control animals with
      increased temperature, whereas heat-shocked animals had a potentiated response
      such that the peak firing frequency was increased. Significant differences were
      also found in the thermosensitivity of the action potential properties between
      control and heat-shocked animals. Heat shock also had a potentiating effect on
      the amplitude of the afterdepolarization. The concurrent increase in peak firing
      frequency and maintenance of action potential properties after heat shock could
      enhance the reliability with which DCMD initiates visually guided behaviors at
      high temperature.

PMID- 15563552
TI  - Tracking whisker and head movements in unrestrained behaving rodents.
AB  - Due to recent advances that enable real-time electrophysiological recordings in
      brains of awake behaving rodents, effective methods for analyzing the large
      amount of behavioral data thus generated, at millisecond resolution, are
      required. We describe a semiautomated, efficient method for accurate tracking of
      head and mystacial vibrissae (whisker) movements in freely moving rodents using
      high-speed video. By tracking the entire length of individual whiskers, we show
      how both location and shape of whiskers are relevant when describing the
      kinematics of whisker movements and whisker interactions with objects during a
      whisker-dependent task and exploratory behavior.

PMID- 15563553
TI  - Saccade dysmetria in head-unrestrained gaze shifts after muscimol inactivation of
      the caudal fastigial nucleus in the monkey.
AB  - Lesions in the caudal fastigial nucleus (cFN) severely impair the accuracy of
      visually guided saccades in the head-restrained monkey. Is the saccade dysmetria
      a central perturbation in issuing commands for orienting gaze (eye in space) or
      is it a more peripheral impairment in generating oculomotor commands? This
      question was investigated in two head-unrestrained monkeys by analyzing the
      effect of inactivating one cFN on horizontal gaze shifts generated from a
      straight ahead fixation light-emitting diode (LED) toward a 40 degrees eccentric
      target LED. After muscimol injections, when viewing the fixation LED, the
      starting position of the head was changed (ipsilesional and upward deviations).
      Ipsilesional gaze shifts were associated with a 24% increase in the eye saccade
      amplitude and a 58% reduction in the amplitude of the head contribution.
      Contralesional gaze shifts were associated with a decrease in the amplitude of
      both eye and head components (40 and 37% reduction, respectively). No correlation
      between the changes in the eye amplitude and in head contribution was observed.
      The amplitude of the complete head movement was decreased for ipsilesional
      movements (57% reduction) and unaffected for contralesional movements. For both
      ipsilesional and contralesional gaze shifts, the changes in eye saccade amplitude
      were strongly correlated with the changes in gaze amplitude and largely accounted
      for the gaze dysmetria. These results indicate a major role of cFN in the
      generation of appropriate saccadic oculomotor commands during head-unrestrained
      gaze shifts.

PMID- 15563554
TI  - Encoding of amplitude and rate of tooth loads by human periodontal afferents from
      premolar and molar teeth.
AB  - Microneurographic recordings were obtained from 20 periodontal mechanoreceptive
      afferents in the inferior alveolar nerve while force profiles of different
      amplitudes and rates were applied to a premolar or the first molar in the most
      sensitive direction. The majority of afferents (17/20) showed a hyperbolic
      relationship between the steady-state discharge rate and the amplitude of the
      stimulating force, featuring a pronounced saturation tendency. These afferents
      were also characterized by a similar decline in dynamic sensitivity with
      increasing amplitude of background force. However, a few afferents (3/20) showed
      nearly linear stimulus-response relationships and a small decline in dynamic
      sensitivity with increasing tooth load. Quantitative models developed for all
      afferents successfully predicted the afferent discharge rates for novel force
      stimulations. Application of the transfer function to chewing forces predicted
      that the discharge rates of periodontal afferents rapidly increased at initial
      tooth contact and continued to discharge as long as the tooth was loaded.
      However, due to the marked saturation tendencies at higher forces, most
      periodontal afferents poorly encoded the magnitude of the strong chewing forces.
      In addition, the discharge rates of a minority of afferents continued to reflect
      the force profile during high chewing forces. The results revealed that
      periodontal afferents of posterior teeth were less sensitive at low tooth loads
      compared with afferents of anterior teeth. During each chewing cycle, periodontal
      afferents may provide information about the mechanical properties of food shortly
      after tooth contact that can be used to scale the muscle commands of the upcoming
      power phase.

PMID- 15563555
TI  - Heterogeneous integration of bilateral whisker signals by neurons in primary
      somatosensory cortex of awake rats.
AB  - Bilateral single-unit recordings in primary somatosensory cortex (S1) of
      anesthetized rats have revealed substantial cross talk between cortical
      hemispheres, suggesting the possibility that behaviorally relevant bilateral
      integration could occur in S1. To determine the extent of bilateral neural
      responses in awake animals, we recorded S1 multi- and single-unit activity in
      head-immobilized rats while stimulating groups of 4 whiskers from the same column
      on both sides of the head. Results from these experiments confirm the widespread
      presence of single units responding to tactile stimuli on either side of the face
      in S1 of awake animals. Quantification of bilateral integration by multiunits
      revealed both facilitative and suppressive integration of bilateral inputs.
      Varying the interval between left and right whisker stimuli between 0 and 120 ms
      showed the temporal integration of bilateral stimuli to be dominated on average
      by suppression at intervals around 30 ms, in agreement with comparable recordings
      in anesthetized animals. Contrary to the anesthetized data, in the awake animals
      we observed a high level of heterogeneity of bilateral responses and a strong
      interaction between synchronous bilateral stimuli. The results challenge the
      traditional conception of highly segregated hemispheric processing channels in
      the rat S1 cortex, and support the hypothesis that callosal cross-projections
      between the two hemispheres mediate rats' known ability to integrate bilateral
      whisker signals.

PMID- 15563556
TI  - Shunting inhibition in accessory optic system neurons.
AB  - The interaction of excitatory and inhibitory inputs to the accessory optic system
      was studied with whole cell recordings in the turtle basal optic nucleus.
      Previous studies have shown that visual patterns, drifting in the same preferred
      direction, evoke excitatory and inhibitory postsynaptic events simultaneously.
      Analysis of the reversal potentials for these events and their pharmacological
      profile suggest that they are mediated by AMPA and GABA(A) receptors,
      respectively. Here, neurons were recorded to study nonlinear interaction between
      excitatory and inhibitory responses evoked by electrical microstimulation of the
      retina and pretectum, respectively. The responses to coincident activation of
      excitatory and inhibitory inputs exhibited membrane shunting in that the
      excitatory response amplitude, adjusted for changes in driving force, was
      attenuated during the onset of the inhibitory response. This nonlinear
      interaction was seen in many but not all stimulus pairings. In some cases,
      attenuation was followed by an augmentation of the excitatory response. For
      comparison, the size of the excitatory response was evaluated during a
      hyperpolarizing current pulse that directly modulated voltage-sensitive channels
      of a slow rectifying I(h) current. Injection of hyperpolarizing current did not
      cause the attenuation of the excitatory synaptic responses. We conclude that
      there is a nonlinear interaction between these excitatory and inhibitory synaptic
      currents that is not due to hyperpolarization itself, but probably is a result of
      their own synaptic conductance changes, i.e., shunting. Since these events are
      evoked by identical visual stimuli, this interaction may play a role in visual
      processing.

PMID- 15563557
TI  - Pyridoxal phosphate and hepatocyte growth factor prevent dialysate-induced
      peritoneal damage.
AB  - Glucose-based peritoneal dialysate (PD) is responsible for increased accumulation
      of advanced glycation end products (AGE) in the peritoneum of continuous
      ambulatory peritoneal dialysis patients. Pyridoxal 5'-phosphate (PLP), a
      derivative of vitamin B(6), protects proteins from glycation. Hepatocyte growth
      factor (HGF) heals damaged tissues in a reciprocal manner against TGF-beta1.
      First, with the use of gas chromatography-mass spectrometry, whether PLP traps 3
      deoxyglucosone (3DG), a major glucose degradation product in PD, was determined.
      Then, whether rat peritoneal tissue damages induced by intraperitoneal
      administration of glucose-based PD is ameliorated by PLP or HGF was examined. In
      vitro incubation with PLP markedly decreased concentration of 3DG in a dose
      dependent manner, demonstrating the 3DG-trapping effect of PLP. The peritoneum of
      PD-treated rats was significantly thickened compared with that of physiologic
      saline-treated rats. Both PLP and HGF prevented the thickening of rat peritoneum
      induced by PD and ameliorated accumulation of AGE and expression of TGF-beta1,
      vascular endothelial growth factor, and type 1 collagen and a number of blood
      vessels. Furthermore, expression of HGF was significantly increased in the
      peritoneum of PLP-treated rats compared with that of PD-treated rats. In
      conclusion, PLP shows 3DG-trapping effect. PLP and HGF prevented peritoneal
      thickening; accumulation of AGE; expression of TGF-beta1, vascular endothelial
      growth factor, and type 1 collagen; and neoangiogenesis in rat peritoneum induced
      by PD.

PMID- 15563558
TI  - Immediate postoperative renal function deterioration in cardiac surgical patients
      predicts in-hospital mortality and long-term survival.
AB  - Postoperative renal function deterioration is a serious complication after
      cardiac surgery with cardiopulmonary bypass and is associated with increased in
      hospital mortality. However, the long-term prognosis of patients with
      postoperative renal deterioration is not fully determined yet. Therefore, both in
      hospital mortality and long-term survival were studied in patients with
      postoperative renal function deterioration. Included were 843 patients who
      underwent cardiac surgery with cardiopulmonary bypass in 1991. Postoperative
      renal function deterioration (increase in serum creatinine in the first
      postoperative week of at least 25%) occurred in 145 (17.2%) patients. In these
      patients, in-hospital mortality was 14.5%, versus 1.1% in patients without renal
      function deterioration (P < 0.001). Multivariate analysis significantly
      associated in-hospital mortality with postoperative renal function deterioration,
      re-exploration, postoperative cerebral stroke, duration of operation, age, and
      diabetes. In patients who were discharged alive, during long-term follow-up (100
      mo), mortality was significantly increased in the patients with renal function
      deterioration (n = 124) as compared with those without renal function
      deterioration (hazard ratio 1.83; 95% confidence interval 1.38 to 3.20). Also
      after adjustment for other independently associated factors, the risk for
      mortality in patients with postoperative renal function deterioration remained
      elevated (hazard ratio 1.63; 95% confidence interval 1.15 to 2.32). The elevated
      risk for long-term mortality was independent of whether renal function had
      recovered at discharge from hospital. It is concluded that postoperative renal
      function deterioration in cardiac surgical patients not only results in increased
      in-hospital mortality but also adversely affects long-term survival.

PMID- 15563559
TI  - Rapamycin markedly slows disease progression in a rat model of polycystic kidney
      disease.
AB  - Increased tubular epithelial cell proliferation is a prerequisite for cyst
      formation and expansion in polycystic kidney disease (PKD). Rapamycin is a potent
      antiproliferative agent. The aim of the present study was to determine the effect
      of rapamycin on tubular cell proliferation, cyst formation, and renal failure in
      the Han:SPRD rat model of PKD. Heterozygous (Cy/+) and littermate control (+/+)
      male rats were weaned at 3 wk of age and then treated with rapamycin 0.2 mg/kg
      per d intraperitoneally or vehicle (ethanol) for 5 wk. Vehicle-treated Cy/+ rats
      had a more than doubling of kidney size compared with +/+ rats. Rapamycin reduced
      the kidney enlargement by 65%. Rapamycin significantly reduced the cyst volume
      density in Cy/+ rats by >40%. Blood urea nitrogen was 59% increased in vehicle
      treated Cy/+ rats compared with +/+ rats. Rapamycin reduced the blood urea
      nitrogen to normal in Cy/+ rats. The number of proliferating cell nuclear antigen
      (PCNA)-positive cells per noncystic tubule was eightfold increased in vehicle
      treated Cy/+ compared with +/+ rats. Rapamycin significantly reduced the number
      of PCNA-positive cells in noncystic tubules of Cy/+ rats. In addition, the number
      of PCNA-positive cells per cyst in Cy/+ rats was significantly reduced by
      rapamycin. In summary, in a rat model of PKD, rapamycin treatment (1) decreases
      proliferation in cystic and noncystic tubules, (2) markedly inhibits renal
      enlargement and cystogenesis, and (3) prevents the loss of kidney function.

PMID- 15563560
TI  - Mouse models of diabetic nephropathy.
AB  - Mice provide an experimental model of unparalleled flexibility for studying
      mammalian diseases. Inbred strains of mice exhibit substantial differences in
      their susceptibility to the renal complications of diabetes. Much remains to be
      established regarding the course of diabetic nephropathy (DN) in mice as well as
      defining those strains and/or mutants that are most susceptible to renal injury
      from diabetes. Through the use of the unique genetic reagents available in mice
      (including knockouts and transgenics), the validation of a mouse model
      reproducing human DN should significantly facilitate the understanding of the
      underlying genetic mechanisms that contribute to the development of DN.
      Establishment of an authentic mouse model of DN will undoubtedly facilitate
      testing of translational diagnostic and therapeutic interventions in mice before
      testing in humans.

PMID- 15563561
TI  - Effect of sodium balance and the combination of ultrafiltration profile during
      sodium profiling hemodialysis on the maintenance of the quality of dialysis and
      sodium and fluid balances.
AB  - Excessive sodium gain is a major hindrance of sodium profiling hemodialysis (HD)
      that offsets the benefit in reducing intradialytic hypotension-related
      discomforts (IHD). Patients who showed frequent IHD (>30% of the sessions; n =
      11) were enrolled in a prospective study that consisted of two phases. In the
      phase 1 study, eight treatment modalities were evaluated: Conventional HD
      (control), sodium balance-positive step-down sodium profiling HD (PS), sodium
      balance-neutral step-down sodium profiling HD (NS), sodium balance-neutral
      alternating sodium profiling HD (NA) without ultrafiltration (UF) profile, and
      all those with UF profile (UF only, PS+U, NS+U, and NA+U). The incidences of
      "dialysis failure," defined as the occurrence of one or more of (1) session
      failure (discontinuation of session <75% of planned time), (2) UF failure (%UF
      achieved <70%), and (3) delivery failure (Kt/V <1.1), were 48.5, 21.2, 42.4,
      39.4, 45.5, 18.2, 21.2, and 18.2% in control, PS, NS, NA, UF only, PS+U, NS+U,
      and NA+U, respectively. Four treatments, PS, PS+U, NS+U, and NA+U, reduced the
      incidence of dialysis failure significantly as compared with control (P < 0.05)
      and were evaluated in the phase 2 study, a randomized controlled 6-wk crossover
      study. Parameters were measured in the steady state after a 6-wk maintenance of
      each treatment. Diffusive sodium gain (DeltaNa) was significantly increased with
      sodium balance-positive profiles with or without UF profile, PS and PS+U (PS 1.9
      +/- 1.1, PS+U 1.7 +/- 1.0 mEq/L; both P < 0.05 to control -0.1 +/- 0.2, NS+U 0.5
      +/- 0.4, NA+U 0.4 +/- 0.2 mEq/L). They also increased the interdialytic weight
      gain (PS 3.8 +/- 0.6, PS+U 4.0 +/- 0.6 kg; both P < 0.05 to control 2.7 +/- 0.6,
      NS+U 3.3 +/- 0.6 kg; both P = NS to NA+U 3.5 +/- 0.6 kg). Predialysis weight and
      the required amount of UF also increased significantly with these sodium balance
      positive profiles. Although the absolute amount of UF was larger with PS and
      PS+U, %UF achieved targeting dry weight was higher with sodium balance-neutral
      profiles with UF profiles, NS+U and NA+U (NS+U 92.7 +/- 3.8, NA+U 93.7 +/- 6.8%;
      both P < 0.05 to control 72.6 +/- 14.0, PS 88.3 +/- 6.6, PS+U 88.2 +/- 8.2%).
      Postdialysis weight was closest to dry weight with these treatments showing Delta
      (postdialysis weight - dry weight) of 0.3 +/- 0.1 and 0.3 +/- 0.2 kg in NS+U and
      NA+U (both P < 0.05 to control 1.0 +/- 0.6 kg; both P = NS to PS 0.5 +/- 0.3,
      PS+U 0.5 +/- 0.4 kg). Incidence of excessive weight gain and subjective
      discomforts during the interdialytic period increased significantly with PS. In
      conclusion, continuous use of sodium balance-positive sodium profiles resulted in
      an undesirable steady state with sodium and fluid expansion offsetting their
      hemodynamic benefit. Sodium balance-neutral sodium profiles in combination with
      UF profile were associated with less sodium and weight gains, better UF
      performance with postdialysis weight closest to dry weight, and fewer
      interdialytic problems with the equivalent hemodynamic benefit. Therefore, it is
      proposed that sodium balance-neutral sodium profiling HD with UF profile is a
      better choice, ensuring the dialysis of quality without sodium gain-related
      complications.

PMID- 15563562
TI  - Fasting plasma total homocysteine levels and mortality and allograft loss in
      kidney transplant recipients: a prospective study.
AB  - Homocysteine is implicated to be an atherogenic amino acid and has been
      associated with increased risk of adverse cardiovascular outcomes. The prognostic
      significance of plasma total homocysteine (tHcy) levels for mortality and
      allograft loss in kidney transplant recipients has not been established. A total
      of 733 kidney transplant recipients who were seen for a routine visit at this
      transplant clinic in 1996 to 1998 were studied prospectively. During that visit,
      clinical information was collected and blood was drawn for laboratory evaluation.
      Information on the previous transplant procedure and the organ donor was obtained
      from the Eurotransplant Foundation database. Patients were followed prospectively
      using the Austrian Dialysis and Transplant Registry. With the use of proportional
      hazards regression, the independent relations of fasting plasma tHcy levels to
      the risk of death from any cause and kidney allograft loss were examined. During
      a median follow-up of 6.1 yr, 154 participants died and 260 kidney allografts
      were lost. After adjustment for several important risk factors, elevated tHcy
      levels (>/=12 micromol/L) were associated with 2.44 times the mortality risk of
      patients with normal tHcy levels (hazards ratio 2.44; 95% confidence interval
      1.45 to 4.12; P < 0.001). Similarly, elevated tHcy levels were associated with
      1.63 times increased risk of kidney allograft loss (hazards ratio 1.63; 95%
      confidence interval 1.09 to 2.44; P = 0.02). In this single-center sample,
      baseline fasting plasma tHcy levels were independently associated with the risk
      of death and kidney allograft loss. The clinical utility of homocysteine-lowering
      therapy, such as multivitamin therapy, to reduce the rates of these end points
      needs to be studied.

PMID- 15563563
TI  - Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999
      to 2000.
AB  - The incidence of kidney failure treatment in the United States increased 57% from
      1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults
      surveyed in 1988 to 1994. The objective of this study was to estimate awareness
      of CKD in the U.S. population during 1999 to 2000 and to determine whether the
      prevalence of CKD in the United States increased compared with 1988 to 1994.
      Analysis was conducted of nationally representative samples of
      noninstitutionalized adults, aged 20 yr and older, in two National Health and
      Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to
      2000 (n = 4101) for prevalence +/- SE. Awareness of CKD is self-reported. Kidney
      function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD
      (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine
      albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using
      the simplified Modification of Diet in Renal Disease Study equation. Self
      reported awareness of weak or failing kidneys in 1999 to 2000 was strongly
      associated with decreased kidney function and albuminuria but was low even in the
      presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59
      ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3%
      at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At
      moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)),
      awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%;
      P = 0.008). The prevalence of moderately or severely decreased kidney function
      (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/-
      0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same
      time, the prevalence of albuminuria (ACR >/= 30 mg/g) in single spot urine
      increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence
      was similar in both surveys (9% using ACR > 30 mg/g for persistent
      microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender
      specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S.
      population is low. In contrast to the dramatic increase in treated kidney
      failure, overall CKD prevalence in the U.S. population has been relatively
      stable.

PMID- 15563564
TI  - Uremia accelerates both atherosclerosis and arterial calcification in
      apolipoprotein E knockout mice.
AB  - Chronic renal failure (CRF) favors the development of atherosclerosis and
      excessive calcification of atheromatous lesions. CRF was induced in
      apolipoprotein E knockout (apoE(-/-)) mice to study (1) a possible acceleration
      of aortic atherosclerosis, (2) the degree and type of vascular calcification, and
      (3) factors involved in the calcification process. For creating CRF, 8-wk-old
      apolipoprotein E gene knockout (apoE(-/-)) mice underwent partial kidney
      ablation. Control animals underwent sham operation. Aortic atherosclerotic
      plaques and calcification were evaluated using quantitative morphologic image
      processing. At 6 wk after nephrectomy, CRF mice had significantly higher serum
      urea, cholesterol, and triglyceride concentrations than non-CRF controls. The
      serum levels of advanced oxidation protein products were elevated in the uremic
      group and were correlated with serum urea levels. Atherosclerotic lesions in
      thoracic aorta were significantly larger in uremic apoE(-/-) mice than in
      nonuremic controls. The relative proportion of calcified area to total surface
      area of both atherosclerotic lesions and lesion-free vascular tissue was
      increased in aortic root of uremic apoE(-/-) mice when compared with controls.
      The calcium deposits were made of hydroxyapatite and calcite crystals. In
      addition, plaques from uremic animals showed a significant increase in collagen
      content, whereas the degree of macrophage infiltration was comparable in both
      groups. There was no difference in mean arterial BP. These findings demonstrate
      that CRF aggravates atherosclerosis in apoE(-/-) mice. Moreover, CRF enhances
      arterial calcification at both atheromatous intimal sites and atheroma-free
      medial sites. We anticipate that this experimental model will be useful to test
      treatment strategies aimed at decreasing the accelerated atherosclerosis and
      arterial calcification in uremia.

PMID- 15563565
TI  - Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are
      indistinguishable from wild-type.
AB  - Mice lacking Ren1c were generated using C57BL/6-derived embryonic stem cells.
      Mice homozygous for Ren1c disruption (Ren1c-/-) are born at the expected ratio,
      but approximately 80% die of dehydration within a few days. The surviving Ren1c-/
      mice have no renin mRNA expression in the kidney, hydronephrosis, thickening of
      renal arterial walls, and fibrosis in the kidney. Plasma renin and angiotensins I
      and II are undetectable. Urinary aldosterone is 6% wild-type. They have low tail
      cuff BP (84 +/- 4 versus 116 +/- 5 mmHg in +/+) and excrete large amounts of
      urine (5.2 +/- 0.8 ml/d, 725 +/- 34 mOsm versus 1.1 +/- 0.1 ml/d, 2460 +/- 170
      mOsm in +/+). After 5 d of drinking 5% dextrose, desmopressin does not increase
      the osmolality of the urine in -/- mice (624 +/- 19 to 656 +/- 25 mOsm), whereas
      in +/+, it increases severalfold (583 +/- 44 to 2630 +/- 174 mOsm). Minipump
      infusion of angiotensin II to Ren1c-/- mice restores BP to wild-type level, but
      preexisting damage to the medulla prevents complete restoration of the ability of
      the kidney to concentrate urine. Heterozygous Ren1c+/- mice, in contrast, are
      indistinguishable from +/+ in BP, urine volume, and osmolality. Kidney renin
      mRNA, the number of kidney cells producing renin, and plasma renin concentration
      in the Ren1c+/- mice are also indistinguishable from +/+. These results
      demonstrate that renin is the only enzyme capable of maintaining plasma
      angiotensins and that renin expression in the kidney is very tightly regulated at
      the mRNA level.

PMID- 15563566
TI  - Maintenance of renal vascular reactivity contributes to acute renal failure
      during endotoxemic shock.
AB  - Septic shock is characterized by hypotension and decreased systemic vascular
      resistance and impaired vascular reactivity. Renal vasoconstriction markedly
      contrasts with sepsis-induced generalized systemic vasodilation, which is
      strongly dependent on nitric oxide. Whether maintained renal vascular reactivity
      to vasoconstrictors contributes to the decrease in renal blood flow (RBF) and GFR
      observed during LPS-induced sepsis was tested by assessment of the acute effects
      of pressor agents on mean arterial pressure (MAP) and renal hemodynamics in
      endotoxemic and control mice. LPS-injected mice displayed lower MAP, RBF, and GFR
      than controls (P < 0.001). Despite a lower MAP, basal renal vascular resistance
      (RVR) was higher during endotoxemia (P < 0.02). Angiotensin II infusion produced
      a weaker MAP response in septic mice (24 versus 37%; P < 0.005), suggesting
      impaired vasoconstriction and hyporeactivity. A similar MAP increase was observed
      between groups during norepinephrine (NE) infusion. The MAP increase to nitric
      oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) was much
      greater in LPS-treated mice (41 versus 15%, P = 0.01), indicating a strong
      influence of nitric oxide in sepsis. In contrast, the RBF and RVR responses to
      angiotensin II, NE, or L-NAME were similar in both groups. Moreover, vasopressin
      produced greater changes in MAP, RBF, and RVR in septic mice than in controls.
      Among the vasoconstrictor challenges, only NE ameliorated the decrease in GFR 14
      h after LPS injection. The in vivo results demonstrate that the renal
      microvasculature displays a normal or enhanced reactivity to constrictor agents
      as compared with nonrenal circulatory beds. Such responsiveness may contribute to
      reduced RBF and GFR during endotoxemia.

PMID- 15563567
TI  - Establishment and maintenance of vascular access in incident hemodialysis
      patients: a prospective cost analysis.
AB  - Despite the importance of hemodialysis vascular access, the cost of vascular
      access care has not been studied in detail. A prospective cost analysis was
      performed among incident hemodialysis patients to determine the cost of vascular
      access care overall and on the basis of access type. Detailed clinical and
      demographic information, as well as data on access type, was collected for all
      local incident hemodialysis patients between July 1, 1999, and November 1, 2001.
      A comprehensive measure of total vascular access costs, including surgery,
      radiology, hospitalization for access complications, physician costs, costs for
      management of outpatient bacteremia, and vascular access monitoring costs, was
      obtained. Costs are reported in 2002 Canadian dollars (1 CAN dollar = 0.69 US
      dollar). A total of 239 consecutive incident hemodialysis patients were
      identified, 49, 157, and 33 of whom were dialyzed exclusively with a catheter or
      had a native arteriovenous fistula or synthetic graft attempted, respectively. In
      year 1, 18.4% of all hospital admissions were for vascular access-related
      complications. The mean cost of all vascular access care in year 1 was 6890 CAN
      dollars(median 4020 dollars; interquartile range [IQR] 2440 dollars to 7540
      dollars). The mean cost of access care per patient-year at risk for maintaining a
      catheter exclusively, attempting an arteriovenous fistula, or attempting a graft
      was 9180 dollars (median 3812 dollars; IQR 2250 dollars to 7762 dollars), 7989
      dollars (median 4641 dollars ; IQR 3035 dollars to 8832 dollars), and 11,685
      dollars (median 8152 dollars; IQR 3395 dollars to 12,908 dollars), respectively
      (P = 0.01). Vascular access care is responsible for a significant proportion of
      health care costs in the first year of hemodialysis. These results support
      clinical practice guidelines that recommend preferential placement of a native
      fistula.

PMID- 15563568
TI  - Influence of race on kidney transplant outcomes within and outside the Department
      of Veterans Affairs.
AB  - Inferior outcomes after kidney transplantation among African Americans are poorly
      understood. It was hypothesized that unequal access to medical care among
      transplant recipients might contribute to worse posttransplantation outcomes
      among African Americans and that racial disparities in kidney transplant outcomes
      would be less pronounced among patients who receive health care within versus
      outside the Department of Veterans Affairs (VA), because eligible veterans who
      receive care within the VA are entitled to receive universal access to care,
      including coverage of prescription drugs. A study cohort of 79,361 patients who
      were undergoing their first kidney transplant in the United States between
      October 1, 1991, and October 31, 2000, was assembled, with follow-up data on
      graft survival obtained through October 31, 2001. After multivariable
      proportional hazards adjustment for a wide range of recipient and donor
      characteristics, African-American patients were at increased risk for graft
      failure compared with non-African-American patients (relative risk [RR] 1.31; 95%
      confidence interval [CI] 1.26 to 1.36). African-American race was associated with
      a similarly increased risk for graft failure among patients who were VA users (RR
      1.31; 95% CI 1.11 to 1.54) and non-VA users (RR 1.31; 95% CI 1.26 to 1.36). In
      conclusion, racial disparities in kidney transplant outcomes seem to persist even
      in a universal access-to-care system such as the VA. Reasons for worse outcomes
      among African Americans require further investigation.

PMID- 15563569
TI  - A clinical score to predict acute renal failure after cardiac surgery.
AB  - The risk of mortality associated with acute renal failure (ARF) after open-heart
      surgery continues to be distressingly high. Accurate prediction of ARF provides
      an opportunity to develop strategies for early diagnosis and treatment. The aim
      of this study was to develop a clinical score to predict postoperative ARF by
      incorporating the effect of all of its major risk factors. A total of 33,217
      patients underwent open-heart surgery at the Cleveland Clinic Foundation (1993 to
      2002). The primary outcome was ARF that required dialysis. The scoring model was
      developed in a randomly selected test set (n = 15,838) and was validated on the
      remaining patients. Its predictive accuracy was compared by area under the
      receiver operating characteristic curve. The score ranges between 0 and 17
      points. The ARF frequency at each score level in the validation set fell within
      the 95% confidence intervals (CI) of the corresponding frequency in the test set.
      Four risk categories of increasing severity (scores 0 to 2, 3 to 5, 6 to 8, and 9
      to 13) were formed arbitrarily. The frequency of ARF across these categories in
      the test set ranged between 0.5 and 22.1%. The score was also valid in predicting
      ARF across all risk categories. The area under the receiver operating
      characteristic curve for the score in the test set was 0.81 (95% CI 0.78 to 0.83)
      and was similar to that in the validation set (0.82; 95% CI 0.80 to 0.85; P =
      0.39). In conclusion, a score is valid and accurate in predicting ARF after open
      heart surgery; along with increasing its clinical utility, the score can help in
      planning future clinical trials of ARF.

PMID- 15563570
TI  - Urinary excretion of beta2-microglobulin and IgG predict prognosis in idiopathic
      membranous nephropathy: a validation study.
AB  - An accurate prediction of the prognosis of patients with idiopathic membranous
      nephropathy (iMN) should allow restriction of immunosuppressive treatment to
      patients who are at highest risk for ESRD. On the basis of retrospective studies,
      it has previously been suggested that the urinary excretions of beta2
      microglobulin (Ubeta2m) and IgG (UIgG) are useful predictors of renal
      insufficiency in patients with iMN. The threshold values of 0.5 micro/min
      (Ubeta2m) and 250 mg/24 h (UIgG) have been validated in a new and larger patient
      cohort. From 1995 onward, 57 patients with iMN (38 men, 19 women; age 48 +/- 16
      yr), a nephrotic syndrome, and a serum creatinine level </=1.5 mg/dl were studied
      prospectively. At baseline, a standardized measurement was carried out to
      determine renal function and protein excretion. The end point renal death was
      defined as a serum creatinine exceeding 1.5 mg/dl or a rise of serum creatinine
      of >50%. Mean (+/-SD) follow-up was 53 +/- 23 mo. Thus far, 25 (44%) of the
      patients have reached the end point renal death. Multivariate analysis confirmed
      Ubeta2m as the strongest independent predictor for the development of renal
      insufficiency. Sensitivity and specificity were 88 and 91%, respectively, for
      Ubeta2m, and both were 88% for UIgG. When the excretions of both proteins were
      combined, specificity improved to 97%. It is concluded that the present data
      validate the accuracy of Ubeta2m and of UIgG in predicting renal outcome in
      patients with iMN. These markers can be used to guide decisions on the start of
      immunosuppressive treatment.

PMID- 15563571
TI  - Impact of graft mass on the clinical outcome of kidney transplants.
AB  - The effect of nephronic mass reduction of kidney transplants has not been
      analyzed specifically in a large cohort. Transplant injuries in cadaver kidney
      graft may have led to an underestimation of the magnitude of this factor. The aim
      of this study was to analyze the consequences of kidney mass reduction on
      transplantation outcome. The weights of 1142 kidney grafts were collected
      prospectively immediately before grafting. Donors and recipients <15 yr of age,
      simultaneous kidney/pancreas grafts, and technical failures before day 7 were
      excluded from the analysis. The analysis was performed on Cockroft-calculated
      creatinine clearance and proteinuria in 964 patients for whom all of the
      necessary information was available. This study reports that the smallest kidneys
      transplanted into the largest recipients (donor kidney weight/recipient body
      weight [DKW/RBW] <2 g/kg, n = 88) increased their clearance by 2.38 ml/min every
      month for 6 mo (P < 0.0001) and by 0.27 ml/min thereafter (P < 0.0001).
      Conversely, creatinine clearance did not change for the largest kidneys
      transplanted into the smallest recipients (DKW/RBW ratios >/=4 g/kg). Next, using
      a Cox model analysis, it was shown that the risk of having a proteinuria >0.5
      g/kg was significantly increased for the low DKW/RBW ratios <2 g/kg with 50% of
      patients having a proteinuria, compared with DKW/RBW ratios >/=4 g/kg (P <
      0.001). In cadaver transplant recipients, graft mass has a rapid impact on graft
      filtration rate and proteinuria. Avoiding major kidney/recipient inadequacy
      should have a significant influence on long-term transplant function.

PMID- 15563572
TI  - Racial and ethnic differences in microalbuminuria prevalence in a diabetes
      population: the pathways study.
AB  - The objective of this study was to determine whether racial or ethnic differences
      in prevalence of diabetic microalbuminuria were observed in a large primary care
      population in which comparable access to health care exists. A cross-sectional
      analysis of survey and automated laboratory data 2969 primary care diabetic
      patients of a large regional health maintenance organization was conducted. Study
      data were analyzed for racial/ethnic differences in microalbuminuria (30 to 300
      mg albumin/g creatinine) and macroalbuminuria (>300 mg albumin/g creatinine)
      prevalence among diabetes registry-identified patients who completed a survey
      that assessed demographics, diabetes care, and depression. Computerized pharmacy,
      hospital, and laboratory data were linked to survey data for analysis.
      Racial/ethnic differences in the odds of microalbuminuria and macroalbuminuria
      were assessed by unconditional logistic regression, stratified by the presence of
      hypertension. Among those tested, the unadjusted prevalence of micro- or
      macroalbuminuria was 30.9%, which was similar among the various racial/ethnic
      groups. Among those without hypertension, microalbuminuria was twofold greater
      (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.14 to 3.53) and
      macroalbuminuria was threefold greater (OR 3.17; 95% CI 1.09 to 9.26) for Asians
      as compared with whites. Among those with hypertension, adjusted odds of
      microalbuminuria were greater for Hispanics (OR 3.82; 95% CI 1.16 to 12.57) than
      whites, whereas adjusted odds of macroalbuminuria were threefold greater for
      blacks (OR 3.32; 95% CI 1.26 to 8.76) than for whites. For most racial/ethnic
      minorities, hypertriglyceridemia was significantly associated with greater odds
      of micro- and macroalbuminuria. Among a large primary care population,
      racial/ethnic differences exist in the adjusted prevalence of microalbuminuria
      and macroalbuminuria depending on hypertension status. In this setting,
      racial/ethnic differences in early diabetic nephropathy were observed despite
      comparable access to diabetes care.

PMID- 15563573
TI  - The fall and rise of parathyroidectomy in U.S. hemodialysis patients, 1992 to
      2002.
AB  - Although the therapeutic approach to managing hyperparathyroidism has changed
      dramatically, it is unknown whether parathyroidectomy rates continue to decline
      in the United States. Parathyroidectomy rates were studied in successive annual
      national cohorts, prevalent on hemodialysis on January 1 of 1992 to 2002, with
      Medicare as primary payer. Parathyroidectomy was defined as International
      Classification of Diseases, Ninth Revision, Clinical Modification code 068. The
      annual incidence of parathyroidectomy was 11.6 per 1000 patient-years in 1992.
      The incidence declined progressively after 1994, reaching a low of 6.8 per 1000
      patient-years in 1998. Rates increased progressively after 1998, reaching 11.8
      per 1000 patient-years in 2002. Using proportional hazards modeling, with
      adjustment for comorbidity and 1992 as the reference group, the lowest adjusted
      hazards ratio, 0.32 (P < 0.0001), was seen in 1998, followed by hazards ratios of
      0.39 (P < 0.0001) in 1999, 0.41 (P < 0.0001) in 2000, 0.52 (P < 0.0001) in 2001,
      and 0.53 (P < 0.0001) in 2002. Other antecedents of parathyroidectomy in
      multivariate models included ESRD network, younger age, female gender, white
      race, absence of diabetes, longer duration of previous hemodialysis, use of
      intravenous vitamin D, previous renal transplantation, several comorbid
      conditions, and parathyroid hormone measurement in the preceding year. With a
      case-control method, parathyroidectomy was associated with higher mortality rates
      immediately after surgery, followed, subsequently, by lower long-term rates.
      Parathyroidectomy rates in U.S. hemodialysis patients increased between 1998 and
      2002, a period in which the therapeutic armamentarium for preventing severe
      hyperparathyroidism expanded considerably.

PMID- 15563574
TI  - Nonresponsiveness of cerebral p53-MDM2 functional circuit in newborn rat pups
      rendered IUGR via uteroplacental insufficiency.
AB  - Severe uteroplacental insufficiency causes cerebral apoptosis in the fetus.
      Moderate uteroplacental insufficiency causes intrauterine growth retardation
      (IUGR) and increases the risk of postnatal neurological morbidity. In the rat,
      uteroplacental insufficiency and IUGR affect cerebral gene expression of Bcl-2
      and predispose the newborn IUGR rat toward cerebral apoptosis when challenged
      with perinatal hypoxia. Expression of Bcl-2, as well as the proapoptotic protein
      Bax, is regulated by p53. p53 also induces MDM2 transcription, which functions to
      limit further p53-induced apoptosis. The predisposition of the IUGR fetus toward
      cerebral apoptosis suggests that the p53-MDM2 "functional" circuit may be
      perturbed in the newborn IUGR rat brain. We hypothesized that MDM2 cerebral
      expression does not increase in response to increased p53 expression or increased
      levels of phospho-p53 (Ser15), an activated form of p53. To prove this
      hypothesis, we induced IUGR through bilateral uterine ligation of the pregnant
      rat. Uteroplacental insufficiency significantly increased p53 mRNA, total p53
      protein, and phospho-p53 (Ser15) protein levels in the brain at term. Increased
      expression of phospho-p53 (Ser15) and terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling-positive cells were localized to the CA1 region
      of the hippocampus, the subcortical and periventricular white matter, and the
      amygdala of the IUGR rat brain. In contrast, uteroplacental insufficiency
      decreased cerebral MDM2 mRNA and phospho-MDM2 (Ser166) protein levels in the IUGR
      rat pups. We conclude that the cerebral MDM2 response to increased p53 expression
      is not present in the newborn IUGR rat pup, and we speculate that this
      contributes to the predisposition of the IUGR fetus toward perinatal and long
      term neurodevelopmental morbidities.

PMID- 15563575
TI  - Green tea extract improves endurance capacity and increases muscle lipid
      oxidation in mice.
AB  - Green tea contains a high level of polyphenolic compounds known as catechins. We
      investigated the effects of green tea extract (GTE), which is rich in catechins,
      on endurance capacity, energy metabolism, and fat oxidation in BALB/c mice over a
      10-wk period. Swimming times to exhaustion for mice fed 0.2-0.5% (wt/wt) GTE were
      prolonged by 8-24%. The effects were dose dependent and accompanied by lower
      respiratory quotients and higher rates of fat oxidation as determined by indirect
      calorimetry. In addition, feeding with GTE increased the level of beta-oxidation
      activity in skeletal muscle. Plasma lactate concentrations in mice fed GTE were
      significantly decreased after exercise, concomitant with increases in free fatty
      acid concentrations in plasma, suggesting an increased lipid use as an energy
      source in GTE-fed mice. Epigallocatechin gallate (EGCG), a major component of tea
      catechins, also enhanced endurance capacity, suggesting that the endurance
      improving effects of GTE were mediated, at least in part, by EGCG. The beta
      oxidation activity and the level of fatty acid translocase/CD36 mRNA in the
      muscle was higher in GTE-fed mice compared with control mice. These results
      indicate that GTE are beneficial for improving endurance capacity and support the
      hypothesis that the stimulation of fatty acid use is a promising strategy for
      improving endurance capacity.

PMID- 15563576
TI  - Effects of chronic baroreceptor unloading on blood pressure in the dog.
AB  - We have developed a new model of chronic baroreceptor unloading (CBU) in the dog.
      Initial characterization of the model indicated that CBU increased mean arterial
      pressure (MAP) by an average of 22 mmHg for 7 days. The goal of the present study
      was to replicate the previous study using telemetry to record MAP continuously
      and to determine the effects of CBU (n = 7) on chronic regulation of MAP. We also
      prepared a group of dogs with sinoaortic denervation (SAD, n = 6) to compare the
      time course of changes in MAP in the two models. Control levels (7 day average +/
      SE) of MAP in the CBU and SAD groups were 94 +/- 2 and 94 +/- 1 mmHg,
      respectively. MAP averaged 124 +/- 8 and 103 +/- 4 mmHg during the first and
      second weeks after SAD (both P < 0.05) and then declined to levels not different
      from control during weeks 3-5. In the CBU group, MAP averaged 120 +/- 4 mmHg
      during the first week, declined to 111 +/- 4 mmHg during the second week, and
      stabilized at 104 mmHg during weeks 3-5 (all P < 0.05 compared with control).
      Plasma norepinephrine levels were increased significantly for the first week
      after SAD and for 2 wk after CBU but were not different from control for the
      remainder of the study. These results indicate that the initial increase in MAP
      after CBU is not sustained but declines to a level that is modestly higher than
      control. However, because MAP did not fall to control levels, the results are
      compatible with the hypothesis that baroreceptor input can influence the long
      term level of MAP.

PMID- 15563577
TI  - Mechanisms of blood pressure variability-induced cardiac hypertrophy and
      dysfunction in mice with impaired baroreflex.
AB  - Enhanced blood pressure variability contributes to left ventricular hypertrophy
      and end-organ damage, even in the absence of hypertension. We hypothesized that
      the greater number of high-blood pressure episodes associated with enhanced blood
      pressure variability causes cardiac hypertrophy and dysfunction by activation of
      mechanosensitive and autocrine pathways. Normotensive mice were subjected to
      sinoaortic baroreceptor denervation (SAD) or sham surgery. Twelve weeks later,
      blood pressure variability was doubled in SAD compared with sham-operated mice.
      Blood pressure did not differ. Cardiac hypertrophy was reflected in greater
      heart/body weight ratios, larger myocyte cross-sectional areas, and greater left
      ventricular collagen deposition. Furthermore, left ventricular atrial and brain
      natriuretic peptide mRNA expression was greater in SAD than in sham-operated
      mice. SAD had higher left ventricular end-diastolic pressures and lower
      myocardial contractility indexes, indicating cardiac dysfunction. Cardiac protein
      content of phosphorylated p125 focal adhesion kinase (p125 FAK) and
      phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was greater in SAD
      than in sham-operated mice, indicating activation of mechanosensitive pathways of
      cardiac hypertrophy. Furthermore, enhanced cardiac renin and transforming growth
      factor-beta1 (TGFbeta1) protein content indicates activation of autocrine
      pathways of cardiac hypertrophy. Adrenal tyrosine hydroxylase protein content and
      the number of renin-positive glomeruli were not different, suggesting that
      sympathetic activation and the systemic renin-angiotensin system did not
      contribute to cardiac hypertrophy. In conclusion, more frequent blood pressure
      rises in subjects with high blood pressure variability activate mechanosensitive
      and autocrine pathways leading to cardiac hypertrophy and dysfunction even in the
      absence of hypertension.

PMID- 15563578
TI  - Assessment of heat production, heat loss, and core temperature during nitrous
      oxide exposure: a new paradigm for studying drug effects and opponent responses.
AB  - Studies using core temperature (T(c)) have contributed greatly to theoretical
      explanations of drug tolerance and its relationship to key features of addiction,
      including dependence, withdrawal, and relapse. Many theoretical accounts of
      tolerance propose that a given drug-induced psychobiological disturbance elicits
      opponent responses that contribute to tolerance development. This proposal and
      its theoretical extensions (e.g., conditioning as a mechanism of chronic
      tolerance) have been inferred from dependent variables, such as T(c), which
      represent the summation of multiple underlying determinants. Direct measurements
      of determinants could increase the understanding of opponent processes in
      tolerance, dependence, and withdrawal. The proximal determinants of T(c) are
      metabolic heat production (HP) and heat loss (HL). We developed a novel system
      for simultaneously quantifying HP (indirect calorimetry), HL (direct gradient
      layer calorimetry), and T(c) (telemetry) during steady-state administrations of
      nitrous oxide (N(2)O), an inhalant with abuse potential that has been previously
      used to study acute and chronic tolerance development to its hypothermia-inducing
      property. Rats were administered 60% N(2)O (n = 18) or placebo gas (n = 16) for 5
      h after a 2-h placebo baseline exposure. On average, N(2)O rapidly but
      transiently lowered HP and increased HL, each by approximately 16% (P < 0.001).
      On average, rats reestablished and maintained thermal equilibrium (HP = HL) at a
      hypothermic T(c) (-1.6 degrees C). However, some rats entered positive heat
      balance (HP > HL) after becoming hypothermic such that acute tolerance developed,
      i.e., T(c) rose despite continued drug administration. This work is the first to
      directly quantify the thermal determinants of T(c) during administration of a
      drug of abuse and establishes a new paradigm for studying opponent processes
      involved in acute and chronic hypothermic tolerance development.

PMID- 15563579
TI  - Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin
      activity but does not activate caspase-3.
AB  - We examined the influence of sepsis on the expression and activity of the calpain
      and caspase systems in skeletal muscle. Sepsis was induced in rats by cecal
      ligation and puncture (CLP). Control rats were sham operated. Calpain activity
      was determined by measuring the calcium-dependent hydrolysis of casein and by
      casein zymography. The activity of the endogenous calpain inhibitor calpastatin
      was measured by determining the inhibitory effect on calpain activity in muscle
      extracts. Protein levels of mu- and m-calpain and calpastatin were determined by
      Western blotting, and calpastatin mRNA was measured by real-time PCR. Caspase-3
      activity was determined by measuring the hydrolysis of the fluorogenic caspase-3
      substrate Ac-DEVD-AMC and by determining protein and mRNA expression for caspase
      3 by Western blotting and real-time PCR, respectively. In addition, the role of
      calpains and caspase-3 in sepsis-induced muscle protein breakdown was determined
      by measuring protein breakdown rates in the presence of specific inhibitors.
      Sepsis resulted in increased muscle calpain activity caused by reduced
      calpastatin activity. In contrast, caspase-3 activity, mRNA levels, and activated
      caspase-3 29-kDa fragment were not altered in muscle from septic rats. Sepsis
      induced muscle proteolysis was blocked by the calpain inhibitor calpeptin but was
      not influenced by the caspase-3 inhibitor Ac-DEVD-CHO. The results suggest that
      sepsis-induced muscle wasting is associated with increased calpain activity,
      secondary to reduced calpastatin activity, and that caspase-3 activity is not
      involved in the catabolic response to sepsis.

PMID- 15563580
TI  - UT-B1 urea transporter is expressed along the urinary and gastrointestinal tracts
      of the mouse.
AB  - Selective transporters account for rapid urea transport across plasma membranes
      of several cell types. UT-B1 urea transporter is widely distributed in rat and
      human tissues. Because mice exhibit high urea turnover and are the preferred
      species for gene engineering, we have delineated UT-B1 tissue expression in
      murine tissues. A cDNA was cloned from BALB/c mouse kidney, encoding a
      polypeptide that differed from C57BL/6 mouse UT-B1 by one residue (Val-8-Ala). UT
      B1 mRNA was detected by RT-PCR in brain, kidney, bladder, testis, lung, spleen,
      and digestive tract (liver, stomach, jejunum, colon). Northern blotting revealed
      seven UT-B1 transcripts in mouse tissues. Immunoblots identified a
      nonglycosylated UT-B1 protein of 29 kDa in most tissues and of 36 and 32 kDa in
      testis and liver, respectively. UT-B1 protein of gastrointestinal tract did not
      undergo N-glycosylation. Immunohistochemistry and in situ hybridization localized
      UT-B1 in urinary tract urothelium (papillary surface, ureter, bladder, and
      urethra), prominently on plasma membranes and restricted to the basolateral area
      in umbrella cells. UT-B1 was found in endothelial cells of descending vasa recta
      in kidney medulla and in astrocyte processes in brain. Dehydration induced by
      water deprivation for 2 days caused a tissue-specific decrease in UT-B1 abundance
      in the urinary bladder and the ureter.

PMID- 15563581
TI  - Intratracheal administration of liposomal clodronate accelerates alveolar
      macrophage reconstitution following fetal liver transplantation.
AB  - To facilitate study of alveolar macrophages in vivo, we developed a method to
      rapidly and efficiently replace resident alveolar macrophages with macrophages of
      a different (donor) genotype. Chimeric mice were generated by lethal irradiation
      followed by fetal liver transplantation (FLT) using green fluorescent protein
      (GFP) transgenic reporter mice as donors. Kinetics of peripheral blood monocyte
      (PBM) and alveolar macrophage reconstitution was determined 4 and 10 weeks post
      FLT by quantifying the percentage of GFP+ cells. To enhance the recruitment of
      donor monocytes into the lung after FLT, mice were treated with intratracheal
      administration of liposomal clodronate to deplete host alveolar macrophages at 6
      weeks post-FLT. PBM reconstitution occurred by 4 weeks after FLT (85.7+/-1.6% of
      CD11b+/Gr-1+ monocytes were GFP+), and minimal alveolar macrophage repopulation
      was observed (9.5% GFP+). By 10 weeks following FLT, 48% of alveolar macrophages
      were GFP+ by immunostaining of macrophages on lung tissue sections, and 55.1 +/-
      1.6% of lung lavage macrophages were GFP+ by fluorescein-activated cell sorter
      analysis. Clodronate treatment resulted in a significant increase in GFP+
      alveolar macrophages 10 weeks after FLT. By immunostaining, 90% of macrophages
      were GFP+ on lung tissue sections and 87.5 +/- 1.1% GFP+ in lung lavage (compared
      with GFP-transgenic controls). The ability of newly recruited alveolar
      macrophages to clear Pseudomonas aeruginosa and activate nuclear factor-kappaB in
      response to Eschericia coli lipopolysaccharide demonstrated normal macrophage
      function. Optimizing this methodology provides an important tool for the study of
      specific genes and their contribution to alveolar macrophage function in vivo.

PMID- 15563582
TI  - Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs
      necessary for binding and activation of the prostaglandin D2 receptor CRTH2.
AB  - The chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)
      receptor, a G protein-coupled receptor that mediates chemotaxis of inflammatory
      cells in response to prostaglandin D2 (PGD2), is hypothesized to play a role in
      Th2-mediated allergic disease. In addition to PGD2, CRTH2 can be activated by
      indomethacin, a nonselective cyclooxygenase inhibitor and widely used
      nonsteroidal anti-inflammatory drug (NSAID). To evaluate the structural features
      that confer CRTH2 binding selectivity, structure-activity relationship analysis
      of arylacetic acid class NSAIDs as CRTH2 receptor ligands was performed.
      Indomethacin, sulindac sulfide, and zomepirac displaced [3H]PGD2 binding at the
      mouse CRTH2 receptor (mCRTH2) with comparable affinity (Ki = 1.5 +/- 0.1, 2.5 +/-
      0.4, and 3.3 +/- 0.3 microM, respectively). The indomethacin metabolite 5'-O
      desmethyl indomethacin (5'-DMI) possessed binding affinity similar to
      indomethacin; however, elimination of the 2-methyl substituent on the indole ring
      resulted in a 10-fold decrease in binding affinity. No binding was detected for
      indole acetic acid and indole derivatives such as tryptophan, serotonin, and 5
      hydroxy indole acetic acid, demonstrating the importance of the N-acyl moiety of
      indomethacin. Neutral derivatives of indomethacin also failed to bind to mCRTH2,
      suggesting that the negatively charged carboxylate moiety participates in a key
      ligand-receptor interaction. Despite similar binding affinities, NSAID-type
      mCRTH2 ligands exhibited variable potencies as mCRTH2 agonists. Sulindac sulfide
      and 5'-DMI inhibited intracellular cyclic AMP ([cAMP]i) generation and stimulated
      cell migration comparable with indomethacin. In contrast, zomepirac did not
      inhibit [cAMP]i generation or stimulate cell migration but weakly antagonized the
      effects of indomethacin on [cAMP]i. Together, these results reveal structural
      features of arylacetic acid NSAIDs that may be exploited for the development of
      selective CRTH2 ligands.

PMID- 15563583
TI  - RGS2 is a mediator of nitric oxide action on blood pressure and vasoconstrictor
      signaling.
AB  - The nitric oxide (NO)-cGMP pathway regulates vascular tone and blood pressure by
      mechanisms that are incompletely understood. RGS2, a GTPase-activating protein
      for Gqalpha that is critical for blood pressure homeostasis, has been suggested
      to serve as an effector of the NO-cGMP pathway that promotes vascular relaxation
      based on studies of aortic rings in vitro. To test this hypothesis and its
      relevance to blood pressure control, we determined whether RGS2 functions as an
      NO effector in smooth muscle of the resistance vasculature. We report that 1) the
      ability of the NO donor sodium nitroprusside to reduce blood pressure is impaired
      in RGS2-/- mice, 2) vasopressin-triggered Ca2+ transients are augmented in smooth
      muscle cells from resistance arteries of RGS2-/- mice, and 3) cGMP analogs fail
      to inhibit vasopressin-triggered Ca2+ transients in smooth muscle cells from
      resistance arteries of RGS2-/- mice even though cGMP-dependent protein kinase
      (PKG)1alpha and PKG1beta are expressed and activated normally. These results
      indicated that the NO-cGMP pathway uses RGS2 as a novel downstream effector to
      promote vascular relaxation by attenuating vasoconstrictor-triggered Ca2+
      signaling in vascular smooth muscle cells. Genetic or epigenetic impairment of
      this mechanism may contribute to the development of hypertension, and augmenting
      it pharmacologically may provide a novel means of treating this disease.

PMID- 15563584
TI  - Transfected beta3- but not beta2-adrenergic receptors regulate cystic fibrosis
      transmembrane conductance regulator activity via a new pathway involving the
      mitogen-activated protein kinases extracellular signal-regulated kinases.
AB  - We have shown previously that in a heterologous mammalian expression system A549
      cells, beta3-adrenoceptor (beta3-AR) stimulation regulates the activity of cystic
      fibrosis transmembrane conductance regulator (CFTR) chloride channel. The present
      investigation was carried out to determine the signaling pathway involved in this
      regulation. A549 cells were intranuclearly injected with plasmids encoding human
      CFTR and beta3-AR. CFTR activity was functionally assessed by
      microcytofluorimetry. The application of 1 microM 4-[3-t-butylamino-2
      hydroxypropoxy]benzimidazol-2-1 hydrochloride (CGP-12177), a beta3-AR agonist,
      produced a CFTR activation that was not abolished by protein kinase A inhibitors.
      In pertussis toxin-pretreated cells, the CFTR activation induced by CGP-12177 was
      abolished. The overexpression of beta-adrenoceptor receptor kinase, an inhibitor
      of betagamma subunits, abolished the CGP-12177-induced CFTR activation,
      suggesting the involvement of betagamma subunits of Gi/o proteins. The
      pretreatment of A549 cells with selective inhibitors of either phosphoinositide 3
      kinase (PI3K), wortmannin, and 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one
      hydrochloride (LY294002), or extracellular signal-regulated kinases 1 and 2
      (ERK1/2) mitogen-activated protein kinase (MAPK), 2'-amino-3'-methoxyflavone
      (PD98059), and 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene
      (U0126), abolished the effects of CGP-12177 on the CFTR activity.
      Immunohistochemical assays showed that only the cells expressing beta3-AR
      exhibited MAPK activation in response to CGP-12177. Furthermore, CFTR activity
      increased in cells pretreated with 10% fetal bovine serum both in A549 cells
      injected only with CFTR and in T84 cells, which endogenously express CFTR,
      indicating that CFTR activity can be regulated by the MAPK independently of the
      beta3-AR stimulation. In conclusion, we have demonstrated that CFTR is regulated
      through a Gi/o/PI3K/ERK1/2 MAPK signaling cascade dependently or not on an
      activation of beta3-ARs. This pathway represents a new regulation for CFTR.

PMID- 15563585
TI  - Commentary: the decline of death--how do we measure and interpret changes in self
      reported health across cultures and time?

PMID- 15563586
TI  - Trends in socioeconomic inequalities in self-assessed health in 10 European
      countries.
AB  - BACKGROUND: Changes over time in inequalities in self-reported health are studied
      for increasingly more countries, but a comprehensive overview encompassing
      several countries is still lacking. The general aim of this article is to
      determine whether inequalities in self-assessed health in 10 European countries
      showed a general tendency either to increase or to decrease between the 1980s and
      the 1990s and whether trends varied among countries. METHODS: Data were obtained
      from nationally representative interview surveys held in Finland, Sweden, Norway,
      Denmark, England, The Netherlands, West Germany, Austria, Italy, and Spain. The
      proportion of respondents with self-assessed health less than 'good' was measured
      in relation to educational level and income level. Inequalities were measured by
      means of age-standardized prevalence rates and odds ratios (ORs). RESULTS:
      Socioeconomic inequalities in self-assessed health showed a high degree of
      stability in European countries. For all countries together, the ORs comparing
      low with high educational levels remained stable for men (2.61 in the 1980s and
      2.54 in the 1990s) but increased slightly for women (from 2.48 to 2.70). The ORs
      comparing extreme income quintiles increased from 3.13 to 3.37 for men and from
      2.43 to 2.86 for women. Increases could be demonstrated most clearly for Italian
      and Spanish men and women, and for Dutch women, whereas inequalities in health in
      the Nordic countries showed no tendency to increase. CONCLUSIONS: The results
      underscore the persistent nature of socioeconomic inequalities in health in
      modern societies. The relatively favourable trends in the Nordic countries
      suggest that these countries' welfare states were able to buffer many of the
      adverse effects of economic crises on the health of disadvantaged groups.

PMID- 15563587
TI  - Much lower prevalence of coronary calcium detected by electron-beam computed
      tomography among men aged 40-49 in Japan than in the US, despite a less favorable
      profile of major risk factors.
AB  - BACKGROUND: Since World War II (WWII), exposures to westernized lifestyle have
      occurred in many non-Western countries, including Japan. National surveys showed
      that risk factor profiles for atherosclerosis around 1990 were similar in men in
      the post WWII birth cohorts in the US and Japan. We compared the degree of
      coronary calcium and other factors in men in the post WWII birth cohort: men aged
      40-49 in the US and Japan. METHODS: We conducted a cross-sectional study
      examining randomly selected 100 men from Kusatsu, Japan, and 100 men from
      Allegheny County, US. Coronary calcium was assessed using electron-beam computed
      tomography. RESULTS: Systolic blood pressure, total cholesterol, low density
      lipoprotein (LDL)-cholesterol, and smoking rates were higher among the Japanese
      (122.6 +/- 14.1 versus 113.7 +/- 9.6 mmHg, P < 0.01; 5.72 +/- 0.90 versus 4.99 +/
      0.81 mmol/l (220.9 +/- 34.6 versus 192.8 +/- 31.3 mg/dl), P < 0.01; 3.52 +/-
      1.01 versus 3.10 +/- 0.78 mmol/l (136.0 +/- 39.0 versus 119.7 +/- 30.0 mg/dl), P
      < 0.01; and 48 versus 15%, P < 0.01, respectively). Triglycerides and fibrinogen
      were similar. High density lipoprotein (HDL)-cholesterol was higher among the
      Japanese. Body mass index, fasting insulin, and C-reactive protein were higher
      among the Americans. Prevalence of coronary artery calcium score >0 was
      strikingly lower among the Japanese than the Americans (13% versus 47%, P <
      0.01). CONCLUSIONS: Much lower prevalence of coronary calcium despite a less
      favourable profile of many major independent risk factors in the Japanese might
      imply that there are strong protective factors against atherosclerosis in the
      Japanese. Further investigation is of critical importance.

PMID- 15563588
TI  - Processing of Notch and amyloid precursor protein by gamma-secretase is spatially
      distinct.
AB  - gamma-Secretase activity is associated with a presenilin (PS)-containing
      macromolecular complex. Whether PS contains the active site of gamma-secretase
      has been controversial. One challenge is to find PS that is engaged in the active
      gamma-secretase complex at the cell surface, where some substrates appear to be
      processed. In this study, we developed an intact cell photolabeling technique
      that allows the direct visualization of active gamma-secretase at the cell
      surface. We demonstrated that active gamma-secretase is present in the plasma
      membrane. Moreover, the PS1 heterodimer is specifically photolabeled at the cell
      surface by a potent inhibitor that binds to only the active gamma-secretase. We
      also explored the cellular processing sites of gamma-secretase for amyloid
      precursor protein (APP) and Notch by using small molecular probes. MRL631, a
      gamma-secretase inhibitor that is unable to penetrate the cell membrane,
      significantly blocks gamma-secretase-mediated Notch cleavage but has little
      effect on APP processing. These results indicate that Notch is processed at the
      cell surface and that the majority of APP is processed by intracellular gamma
      secretase. Furthermore, the fact that inhibitors first target gamma-secretase in
      the plasma membrane for Notch processing, and not for APP, will have important
      implications for drug development to treat Alzheimer's disease and cancer.

PMID- 15563589
TI  - Printed covalent glycan array for ligand profiling of diverse glycan binding
      proteins.
AB  - Here we describe a glycan microarray constructed by using standard robotic
      microarray printing technology to couple amine functionalized glycans to an amino
      reactive glass slide. The array comprises 200 synthetic and natural glycan
      sequences representing major glycan structures of glycoproteins and glycolipids.
      The array has remarkable utility for profiling the specificity of a diverse range
      of glycan binding proteins, including C-type lectins, siglecs, galectins,
      anticarbohydrate antibodies, lectins from plants and microbes, and intact
      viruses.

PMID- 15563590
TI  - Combinatorial antibody libraries from cancer patients yield ligand-mimetic Arg
      Gly-Asp-containing immunoglobulins that inhibit breast cancer metastasis.
AB  - Combinatorial antibody libraries have the potential to display the entire
      immunological record of an individual, allowing one to detect and recover any
      antibody ever made, irrespective of whether it is currently being produced. We
      have termed this the "fossil record" of an individual's antibody response. To
      determine whether cancer patients have ever made antibodies with disease-fighting
      potential, we screened combinatorial antibody libraries from cancer patients for
      immunoglobulins that can identify metastatic tumor cells. This strategy yielded
      human antibodies specific for the activated conformation of the adhesion receptor
      integrin alphavbeta3 that is associated with a metastatic phenotype. In a
      remarkable example of convergent evolution, two of these antibodies were shown to
      contain the Arg-Gly-Asp integrin recognition motif of the natural ligand within
      the third complementarity-determining region of the heavy chain. These antibodies
      interfered with lung colonization by human breast cancer cells in a mouse model
      and inhibited existing metastatic disease. Our data imply that, at least at some
      time, these antibodies were part of a patient's surveillance system against
      metastatic cells, targeting the activated conformer of integrin alphavbeta3 and
      disrupting its functions. The ligand-mimetic nature of these antibodies, combined
      with specificity for a single receptor, is unique in the integrin-ligand
      repertoire. The convergent evolution of critical sequences in antibodies and
      other ligands that bind to the same target means that the immune response has
      sufficient power to find a best chemical solution for the optimization of binding
      energy, even though antibodies evolve in real time, as compared with billions of
      years for the natural ligand.

PMID- 15563591
TI  - Glycine as a D-amino acid surrogate in the K(+)-selectivity filter.
AB  - The K(+) channel-selectivity filter consists of two absolutely conserved glycine
      residues. Crystal structures show that the first glycine in the selectivity
      filter, Gly-77 in KcsA, is in a left-handed helical conformation. Although the
      left-handed helical conformation is not favorable for the naturally occurring L
      amino acids, it is favorable for the chirally opposite D-amino acids. Here, we
      demonstrate that Gly-77 can be replaced by D-Ala with almost complete retention
      of function. In contrast, substitution with an L-amino acid results in a
      nonfunctional channel. This finding suggests that glycine is used as a surrogate
      D-amino acid in the selectivity filter. The absolute conservation of glycine in
      the K(+)-selectivity filter can be explained as a result of glycine being the
      only natural amino acid that can play this role.

PMID- 15563592
TI  - Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage
      and in endochondral ossification.
AB  - Collagenase-3 (MMP13), a member of the matrix metalloproteinase (MMP) family of
      neutral endopeptidases, is expressed in the skeleton during embryonic development
      and is highly overexpressed in human carcinomas and in chondrocytes and synovial
      cells in rheumatoid arthritis and osteoarthritis. To determine the functional
      roles of Mmp13, we generated Mmp13-null mice that showed profound defects in
      growth plate cartilage with markedly increased hypertrophic domains as well as
      delay in endochondral ossification and formation and vascularization of primary
      ossification centers. Absence of Mmp13 resulted in significant interstitial
      collagen accumulation due, in part, to the lack of appropriate collagenase
      mediated cleavage that normally occurs in growth plates and primary ossification
      centers. Cartilaginous growth plate abnormalities persisted in adult mice and
      phenocopied defects observed in human hereditary chondrodysplasias. Our findings
      demonstrate a unique role of Mmp13 in skeletal development.

PMID- 15563593
TI  - The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and
      inhibit its activation of the IFN-beta promoter.
AB  - Most paramyxoviruses circumvent the IFN response by blocking IFN signaling and
      limiting the production of IFN by virus-infected cells. Here we report that the
      highly conserved cysteine-rich C-terminal domain of the V proteins of a wide
      variety of paramyxoviruses binds melanoma differentiation-associated gene 5 (mda
      5) product. mda-5 is an IFN-inducible host cell DExD/H box helicase that contains
      a caspase recruitment domain at its N terminus. Overexpression of mda-5
      stimulated the basal activity of the IFN-beta promoter in reporter gene assays
      and significantly enhanced the activation of the IFN-beta promoter by
      intracellular dsRNA. Both these activities were repressed by coexpression of the
      V proteins of simian virus 5, human parainfluenza virus 2, mumps virus, Sendai
      virus, and Hendra virus. Similar results to the reporter assays were obtained by
      measuring IFN production. Inhibition of mda-5 by RNA interference or by dominant
      interfering forms of mda-5 significantly inhibited the activation of the IFN-beta
      promoter by dsRNA. It thus appears that mda-5 plays a central role in an
      intracellular signal transduction pathway that can lead to the activation of the
      IFN-beta promoter, and that the V proteins of paramyxoviruses interact with mda-5
      to block its activity.

PMID- 15563594
TI  - A requirement for breast-cancer-associated gene 1 (BRCA1) in the spindle
      checkpoint.
AB  - BRCA1-associated breast cancer exhibits significantly higher levels of
      chromosomal abnormalities than sporadic breast cancers. However, the molecular
      mechanisms regarding the roles of BRCA1 in maintaining genome integrity remain
      elusive. By using a mouse model deficient for Brca1 full-length isoform
      (Brca1(Delta11/Delta11)), we found that Brca1(Delta11/Delta11) cells displayed
      decreased expression of a number of genes that are involved in the spindle
      checkpoint, including Mad2, which is a key component of spindle checkpoint that
      inhibits anaphase-promoting complex. We showed that Brca1(Delta11/Delta11) cells
      failed to arrest at metaphase in the presence of nocodazole and underwent
      apoptosis because of activation of p53. Consistently, reconstitution of Mad2 in
      Brca1(Delta11/Delta11) cells partially restored the spindle checkpoint and
      attenuated apoptosis. By using UBR60 cells, which carry tetracycline-regulated
      expression of BRCA1, we demonstrated that BRCA1 binds to transcription factor OCT
      1 and up-regulates the transcription of MAD2. Furthermore, we showed that the
      induction of BRCA1 to endogenous MAD2 or transfected MAD2 luciferase reporter in
      UBR60 cells was completely inhibited by acute suppression of BRCA1 by RNA
      interference. These data reveal a role of BRCA1 in maintaining genome integrity
      by interplaying with p53 and genes that are involved in the spindle checkpoint
      and apoptosis.

PMID- 15563595
TI  - Imaging of receptor trafficking by using alpha-bungarotoxin-binding-site-tagged
      receptors.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors mediate
      excitatory synaptic transmission and are dynamically regulated during synaptic
      plasticity in the CNS. The membrane trafficking of AMPA receptors to synapses is
      critical for the regulation of the efficacy of excitatory synaptic transmission.
      Direct imaging of AMPA receptors in various cell compartments is important to
      dissecting the regulation of distinct steps in receptor membrane trafficking. In
      this study, we have developed an approach for the imaging of receptor trafficking
      with subunits tagged with a 13-aa alpha-bungarotoxin (BTX)-binding site (BBS).
      The small polypeptide neurotoxin BTX has been used for decades to study the
      nicotinic acetylcholine receptor. Similar high-affinity ligands are rarely
      available for most receptors. Engineering the BBS tag into receptor subunits
      allowed the high-affinity binding of fluorescent, radioactive, and biotinylated
      BTX to the tagged receptor subunits. By using this approach, the total receptor
      expression, surface expression, internalization, and insertion of receptors into
      the plasma membrane could be visualized and quantified in fixed or live cells
      including cultured neurons. The BBS tag is a flexible approach for labeling
      membrane proteins and studying their dynamic trafficking.

PMID- 15563596
TI  - Coordinated assembly of human translation initiation complexes by the hepatitis C
      virus internal ribosome entry site RNA.
AB  - Protein synthesis in all cells begins with recruitment of the small ribosomal
      subunit to the initiation codon in a messenger RNA. In some eukaryotic viruses,
      RNA upstream of the coding region forms an internal ribosome entry site (IRES)
      that directly binds to the 40S ribosomal subunit and enables translation
      initiation in the absence of many canonical translation initiation factors. The
      hepatitis C virus (HCV) IRES RNA requires just two initiation factors, eukaryotic
      initiation factor (eIF) 2 and eIF3, to form preinitiation 48S ribosomal complexes
      that subsequently assemble into translation-competent ribosomes. Using an RNA
      based affinity purification approach, we show here that HCV IRES RNA facilitates
      eIF2 function through its interactions with eIF3 and the 40S ribosomal subunit.
      Although the wild-type IRES assembles normally into 48S and 80S ribosomal
      complexes in human cell extract, mutant IRES RNAs become trapped at the 48S
      assembly stage. Trapped 48S complexes formed by IRES mutants with reduced eIF3
      binding affinity nonetheless contain eIF3, consistent with inherent eIF3-40S
      subunit affinity. Intriguingly, however, one of these IRES mutants prevents
      stable association of both eIF3 and eIF2, preventing initiator tRNA deposition
      and explaining the block in 80S assembly. In contrast, an IRES mutant unable to
      induce a conformational change in the 40S subunit, as observed previously by
      single-particle cryoelectron microscopy, blocks 80S formation at a later stage in
      assembly. These data suggest that the IRES RNA coordinates interactions of eIF3
      and eIF2 on the ribosome required to position the initiator tRNA on the mRNA in
      the ribosomal peptidyl-tRNA site (P site).

PMID- 15563597
TI  - Combinatorics of traces of Hecke operators.
AB  - We investigate the combinatorial properties of the traces of the nth Hecke
      operators on the spaces of weight 2k cusp forms of level N. We establish examples
      in which these traces are expressed in terms of classical objects in enumerative
      combinatorics (e.g., tilings and Motzkin paths). We establish in general that
      Hecke traces are explicit rational linear combinations of values of Gegenbauer
      (also known as ultraspherical) polynomials. These results arise from "packaging"
      the Hecke traces into power series in weight aspect. These generating functions
      are easily computed by using the Eichler-Selberg trace formula.

PMID- 15563598
TI  - The mechanism of ammonia transport based on the crystal structure of AmtB of
      Escherichia coli.
AB  - Ammonium is one of the most important nitrogen sources for bacteria, fungi, and
      plants, but it is toxic to animals. The ammonium transport proteins (methylamine
      permeases/ammonium transporters/rhesus) are present in all domains of life;
      however, functional studies with members of this family have yielded
      controversial results with respect to the chemical identity (NH(4)(+) or NH(3))
      of the transported species. We have solved the structure of wild-type AmtB from
      Escherichia coli in two crystal forms at 1.8- and 2.1-A resolution, respectively.
      Substrate transport occurs through a narrow mainly hydrophobic pore located at
      the center of each monomer of the trimeric AmtB. At the periplasmic entry, a
      binding site for NH(4)(+) is observed. Two phenylalanine side chains (F107 and
      F215) block access into the pore from the periplasmic side. Further into the
      pore, the side chains of two highly conserved histidine residues (H168 and H318)
      bridged by a H-bond lie adjacent, with their edges pointing into the cavity.
      These histidine residues may facilitate the deprotonation of an ammonium ion
      entering the pore. Adiabatic free energy calculations support the hypothesis that
      an electrostatic barrier between H168 and H318 hinders the permeation of cations
      but not that of the uncharged NH(3.) The structural data and energetic
      considerations strongly indicate that the methylamine permeases/ammonium
      transporters/rhesus proteins are ammonia gas channels. Interestingly, at the
      cytoplasmic exit of the pore, two different conformational states are observed
      that might be related to the inactivation mechanism by its regulatory partner.

PMID- 15563599
TI  - A digital technique for art authentication.
AB  - We describe a computational technique for authenticating works of art,
      specifically paintings and drawings, from high-resolution digital scans of the
      original works. This approach builds a statistical model of an artist from the
      scans of a set of authenticated works against which new works then are compared.
      The statistical model consists of first- and higher-order wavelet statistics. We
      show preliminary results from our analysis of 13 drawings that at various times
      have been attributed to Pieter Bruegel the Elder; these results confirm expert
      authentications. We also apply these techniques to the problem of determining the
      number of artists that may have contributed to a painting attributed to Pietro
      Perugino and again achieve an analysis agreeing with expert opinion.

PMID- 15563600
TI  - Liver-targeted disruption of Apc in mice activates beta-catenin signaling and
      leads to hepatocellular carcinomas.
AB  - Although inappropriate activation of the Wnt/beta-catenin pathway has been
      implicated in the development of hepatocellular carcinoma (HCC), the role of this
      signaling in liver carcinogenesis remains unclear. To investigate this issue, we
      constructed a mutant mouse strain, Apc(lox/lox), in which exon 14 of the tumor
      suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences.
      i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high
      multiplicity [10(9) plaque-forming units (pfu) per mouse] inactivated the Apc
      gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia,
      and rapid mortality. beta-Catenin signaling activation was demonstrated by
      nuclear and cytoplasmic accumulation of beta-catenin in the hepatocytes and by
      the induction of beta-catenin target genes (glutamine synthetase, glutamate
      transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin
      2) in the liver. To test a long-term oncogenic effect, we inoculated mice with
      lower doses of AdCre (0.5 x 10(9) pfu per mouse), compatible with both survival
      and persistence of beta-catenin-activated cells. In these conditions, 67% of mice
      developed HCC. beta-Catenin signaling was strongly activated in these Apc
      inactivated HCCs. The HCCs were well, moderately, or poorly differentiated.
      Indeed, their histological and molecular features mimicked human HCC. Thus,
      deletion of Apc in the liver provides a valuable model of human HCC, and, in this
      model, activation of the Wnt/beta-catenin pathway by invalidation of Apc is
      required for liver tumorigenesis.

PMID- 15563601
TI  - Social supports and serotonin transporter gene moderate depression in maltreated
      children.
AB  - In this study, measures of the quality and availability of social supports were
      found to moderate risk for depression associated with a history of maltreatment
      and the presence of the short (s) allele of the serotonin transporter gene
      promoter polymorphism (5-HTTLPR). The present investigation (i) replicates
      research in adults showing that 5-HTTLPR variation moderates the development of
      depression after stress, (ii) extends the finding to children, and (iii)
      demonstrates the ability of social supports to further moderate risk for
      depression. Maltreated children with the s/s genotype and no positive supports
      had the highest depression ratings, scores that were twice as high as the non
      maltreated comparison children with the same genotype. However, the presence of
      positive supports reduced risk associated with maltreatment and the s/s genotype,
      such that maltreated children with this profile had only minimal increases in
      their depression scores. These findings are consistent with emerging preclinical
      and clinical data suggesting that the negative sequelae associated with early
      stress are not inevitable. Risk for negative outcomes may be modified by both
      genetic and environmental factors, with the quality and availability of social
      supports among the most important environmental factors in promoting resiliency
      in maltreated children, even in the presence of a genotype expected to confer
      vulnerability for psychiatric disorder.

PMID- 15563602
TI  - The high- and low-affinity receptor binding sites of growth hormone are
      allosterically coupled.
AB  - Growth hormone regulates its biological properties via a sequential hormone
      induced receptor homodimerization mechanism. Using a mutagenesis-scanning
      analysis of 81 single and 32 pairwise double mutations, we show that the
      hormone's two spatially distal receptor binding sites (Site1 and Site2) are
      allosterically coupled. These allosteric effects are focused among a relatively
      few residues centered around the interaction between Asp-116 of the hormone and
      Trp-169 of the receptor in Site2. A rearrangement of this interaction triggered
      by mutations in Site1 produces both a major conformation and energetic
      reorganization of Site2, surprisingly without a reduction in overall binding
      affinity. Additionally, the data suggest a change in the conformational dynamics
      of several groups in Site2 that appear to be important in defining the Site2
      interaction. Changes in binding energy of the affected Site2 residues usually
      range in magnitude from 3- to 60-fold, but in one case are as large as 10(4).

PMID- 15563603
TI  - Molecular characterization of radial spoke subcomplex containing radial spoke
      protein 3 and heat shock protein 40 in sperm flagella of the ascidian Ciona
      intestinalis.
AB  - Members of the heat-shock protein (HSP)40 regulate the protein folding activity
      of HSP70 proteins and help the functional specialization of this molecular
      chaperone system in various types of cellular events. We have recently identified
      Hsp40 as a component of flagellar axoneme in the ascidian Ciona intestinalis,
      suggesting a correlation between Hsp40 related chaperone system and flagellar
      function. In this study, we have found that Ciona 37-kDa Hsp40 is extracted from
      KCl-treated axonemes with 0.5 M KI solution and comigrates with radial spoke
      protein (RSP)3 along with several proteins as a complex through gel filtration
      and ion exchange columns. Peptide mass fingerprinting with matrix-assisted laser
      desorption ionization/time of flight/mass spectrometry revealed that other
      proteins in the complex include a homolog of sea urchin spokehead protein
      (homolog of RSP4/6), a membrane occupation and recognition nexus repeat protein
      with sequence similarity with meichroacidin, and a functionally unknown 33-kDa
      protein. A spoke head protein, LRR37, is not included in the complex, suggesting
      that the complex constructs the stalk of radial spoke. Immunoelectron microscopy
      indicates that Hsp40 is localized in the distal portion of spoke stalk, possibly
      at the junction between spoke head and the stalk.

PMID- 15563604
TI  - Munc18-1 regulates early and late stages of exocytosis via syntaxin-independent
      protein interactions.
AB  - Sec1/Munc18 (SM) proteins are involved in various intracellular membrane
      trafficking steps. Many SM proteins bind to appropriate syntaxin homologues
      involved in these steps, suggesting that SM proteins function as syntaxin
      chaperones. Organisms with mutations in SM genes, however, exhibit defects in
      either early (docking) or late (fusion) stages of exocytosis, implying that SM
      proteins may have multiple functions. To gain insight into the role of SM
      proteins, we introduced mutations modeled on those identified in Caenorhabditis
      elegans, Drosophila melanogaster, and Saccharomyces cerevisiae into mammalian
      Munc18-1. As expected, several mutants exhibited reduced binding to syntaxin1A.
      However, three mutants displayed wild-type syntaxin binding affinities,
      indicating syntaxin-independent defects. Expression of these mutants in
      chromaffin cells either increased the rate and extent of exocytosis or altered
      the kinetics of individual release events. This latter effect was associated with
      a reduced Mint binding affinity in one mutant, implying a potential mechanism for
      the observed alteration in release kinetics. Furthermore, this phenotype
      persisted when the mutation was combined with a second mutation that greatly
      reduced syntaxin binding affinity. These results clarify the data on the function
      of SM proteins in mutant organisms and indicate that Munc18-1 controls multiple
      stages of exocytosis via both syntaxin-dependent and -independent protein
      interactions.

PMID- 15563605
TI  - Fibronectin matrix turnover occurs through a caveolin-1-dependent process.
AB  - Extracellular matrix remodeling occurs during development, tissue repair, and in
      a number of pathologies, including fibrotic disorders, hypertension, and
      atherosclerosis. Extracellular matrix remodeling involves the complex interplay
      between extracellular matrix synthesis, deposition, and degradation. Factors that
      control these processes are likely to play key roles in regulating physiological
      and pathological extracellular matrix remodeling. Our data show that fibronectin
      polymerization into the extracellular matrix regulates the deposition and
      stability of other extracellular matrix proteins, including collagen I and
      thrombospondin-1 (Sottile and Hocking, 2002. Mol. Biol. Cell 13, 3546). In the
      absence of continual fibronectin polymerization, there is a loss of fibronectin
      matrix fibrils, and increased levels of fibronectin degradation. Fibronectin
      degradation occurs intracellularly after endocytosis and can be inhibited by
      chloroquine, an inhibitor of lysosomal degradation, and by caveolae-disrupting
      agents. Down-regulation of caveolin-1 by RNAi inhibits loss of fibronectin matrix
      fibrils, fibronectin internalization, and fibronectin degradation; these
      processes can be restored by reexpression of caveolin-1. These data show that
      fibronectin matrix turnover occurs through a caveolin-1-dependent process.
      Caveolin-1 regulation of fibronectin matrix turnover is a novel mechanism
      regulating extracellular matrix remodeling.

PMID- 15563606
TI  - The Caenorhabditis elegans UNC-14 RUN domain protein binds to the kinesin-1 and
      UNC-16 complex and regulates synaptic vesicle localization.
AB  - Kinesin-1 is a heterotetramer composed of kinesin heavy chain (KHC) and kinesin
      light chain (KLC). The Caenorhabditis elegans genome has a single KHC, encoded by
      the unc-116 gene, and two KLCs, encoded by the klc-1 and klc-2 genes. We show
      here that UNC-116/KHC and KLC-2 form a complex orthologous to conventional
      kinesin-1. KLC-2 also binds UNC-16, the C. elegans JIP3/JSAP1 JNK-signaling
      scaffold protein, and the UNC-14 RUN domain protein. The localization of UNC-16
      and UNC-14 depends on kinesin-1 (UNC-116 and KLC-2). Furthermore, mutations in
      unc-16, klc-2, unc-116, and unc-14 all alter the localization of cargos
      containing synaptic vesicle markers. Double mutant analysis is consistent with
      these four genes functioning in the same pathway. Our data support a model
      whereby UNC-16 and UNC-14 function together as kinesin-1 cargos and regulators
      for the transport or localization of synaptic vesicle components.

PMID- 15563607
TI  - The yeast par-1 homologs kin1 and kin2 show genetic and physical interactions
      with components of the exocytic machinery.
AB  - Kin1 and Kin2 are Saccharomyces cerevisiae counterparts of Par-1, the
      Caenorhabditis elegans kinase essential for the establishment of polarity in the
      one cell embryo. Here, we present evidence for a novel link between Kin1, Kin2,
      and the secretory machinery of the budding yeast. We isolated KIN1 and KIN2 as
      suppressors of a mutant form of Rho3, a Rho-GTPase acting in polarized
      trafficking. Genetic analysis suggests that KIN1 and KIN2 act downstream of the
      Rab-GTPase Sec4, its exchange factor Sec2, and several components of the vesicle
      tethering complex, the Exocyst. We show that Kin1 and Kin2 physically interact
      with the t-SNARE Sec9 and the Lgl homologue Sro7, proteins acting at the final
      stage of exocytosis. Structural analysis of Kin2 reveals that its catalytic
      activity is essential for its function in the secretory pathway and implicates
      the conserved 42-amino acid tail at the carboxy terminal of the kinase in
      autoinhibition. Finally, we find that Kin1 and Kin2 induce phosphorylation of t
      SNARE Sec9 in vivo and stimulate its release from the plasma membrane. In
      summary, we report the finding that yeast Par-1 counterparts are associated with
      and regulate the function of the exocytic apparatus via phosphorylation of Sec9.

PMID- 15563608
TI  - Quantitative imaging of single live cells reveals spatiotemporal dynamics of
      multistep signaling events of chemoattractant gradient sensing in Dictyostelium.
AB  - Activation of G-protein-coupled chemoattractant receptors triggers dissociation
      of Galpha and Gbetagamma subunits. These subunits induce intracellular responses
      that can be highly polarized when a cell experiences a gradient of
      chemoattractant. Exactly how a cell achieves this amplified signal polarization
      is still not well understood. Here, we quantitatively measure temporal and
      spatial changes of receptor occupancy, G-protein activation by FRET imaging, and
      PIP3 levels by monitoring the dynamics of PH(Crac)-GFP translocation in single
      living cells in response to different chemoattractant fields. Our results
      provided the first direct evidence that G-proteins are activated to different
      extents on the cell surface in response to asymmetrical stimulations. A stronger,
      uniformly applied stimulation triggers not only a stronger G-protein activation
      but also a faster adaptation of downstream responses. When naive cells (which
      have not experienced chemoattractant) were abruptly exposed to stable cAMP
      gradients, G-proteins were persistently activated throughout the entire cell
      surface, whereas the response of PH(Crac)-GFP translocation surprisingly
      consisted of two phases, an initial transient and asymmetrical translocation
      around the cell membrane, followed by a second phase producing a highly polarized
      distribution of PH(Crac)-GFP. We propose a revised model of gradient sensing,
      suggesting an important role for locally controlled components that inhibit
      PI3Kinase activity.

PMID- 15563609
TI  - The role of the kinesin motor KipA in microtubule organization and polarized
      growth of Aspergillus nidulans.
AB  - Polarized growth in filamentous fungi requires the integrity of the microtubule
      (MT) cytoskeleton. We found that growing MTs in Aspergillus nidulans merge at the
      center of fast growing tips and discovered that a kinesin motor protein, KipA,
      related to Tea2p of Schizosaccharomyces pombe, is required for this process. In a
      DeltakipA strain, MT plus ends reach the tip but show continuous lateral
      movement. Hyphae lose directionality and grow in curves, apparently due to
      mislocalization of the vesicle supply center (Spitzenkorper) in the apex. Green
      fluorescent protein (GFP)-KipA accumulates at MT plus ends, whereas a KipA rigor
      mutant protein, GFP-KipA(G223E), coated MTs evenly. These findings suggest that
      KipA requires its intrinsic motor activity to reach the MT plus end. Using KipA
      as an MT plus-end marker, we found bidirectional organization of MTs and
      determined the locations of microtubule organizing centers at nuclei, in the
      cytoplasm, and at septa.

PMID- 15563610
TI  - ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis
      elegans polycystin signaling.
AB  - Caenorhabditis elegans is a powerful model to study the molecular basis of
      autosomal dominant polycystic kidney disease (ADPKD). ADPKD is caused by
      mutations in the polycystic kidney disease (PKD)1 or PKD2 gene, encoding
      polycystin (PC)-1 or PC-2, respectively. The C. elegans polycystins LOV-1 and PKD
      2 are required for male mating behaviors and are localized to sensory cilia. The
      function of the evolutionarily conserved polycystin/lipoxygenase/alpha-toxin
      (PLAT) domain found in all PC-1 family members remains an enigma. Here, we report
      that ATP-2, the beta subunit of the ATP synthase, physically associates with the
      LOV-1 PLAT domain and that this interaction is evolutionarily conserved. In
      addition to the expected mitochondria localization, ATP-2 and other ATP synthase
      components colocalize with LOV-1 and PKD-2 in cilia. Disrupting the function of
      the ATP synthase or overexpression of atp-2 results in a male mating behavior
      defect. We further show that atp-2, lov-1, and pkd-2 act in the same molecular
      pathway. We propose that the ciliary localized ATP synthase may play a previously
      unsuspected role in polycystin signaling.

PMID- 15563611
TI  - A sorting nexin PpAtg24 regulates vacuolar membrane dynamics during pexophagy via
      binding to phosphatidylinositol-3-phosphate.
AB  - Diverse cellular processes such as autophagic protein degradation require
      phosphoinositide signaling in eukaryotic cells. In the methylotrophic yeast
      Pichia pastoris, peroxisomes can be selectively degraded via two types of
      pexophagic pathways, macropexophagy and micropexophagy. Both involve membrane
      fusion events at the vacuolar surface that are characterized by internalization
      of the boundary domain of the fusion complex, indicating that fusion occurs at
      the vertex. Here, we show that PpAtg24, a molecule with a phosphatidylinositol 3
      phosphate-binding module (PX domain) that is indispensable for pexophagy,
      functions in membrane fusion at the vacuolar surface. CFP-tagged PpAtg24
      localized to the vertex and boundary region of the pexophagosome-vacuole fusion
      complex during macropexophagy. Depletion of PpAtg24 resulted in the blockage of
      macropexophagy after pexophagosome formation and before the fusion stage. These
      and other results suggest that PpAtg24 is involved in the spatiotemporal
      regulation of membrane fusion at the vacuolar surface during pexophagy via
      binding to phosphatidylinositol 3-phosphate, rather than the previously suggested
      function in formation of the pexophagosome.

PMID- 15563613
TI  - Dimeric novel HSP40 is incorporated into the radial spoke complex during the
      assembly process in flagella.
AB  - The radial spoke is a stable structural complex in the 9 + 2 axoneme for the
      control of flagellar motility. However, the spokes in Chlamydomonas mutant pf24
      are heterogeneous and unstable, whereas several spoke proteins are reduced
      differentially. To elucidate the defective mechanism, we clone RSP16, a prominent
      spoke protein diminished in pf24 axonemes. Unexpectedly, RSP16 is a novel HSP40
      member of the DnaJ superfamily that assists chaperones in various protein-folding
      related processes. Importantly, RSP16 is uniquely excluded from the 12S spoke
      precursor complex that is packaged in the cell body and transported toward the
      flagellar tip to be converted into mature 20S axonemal spokes. Rather, RSP16,
      transported separately, joins the precursor complex in flagella. Furthermore,
      RSP16 molecules in vitro and in flagella form homodimers, a characteristic
      required for the cochaperone activity of HSP40. We postulate that the spoke HSP40
      operates as a cochaperone to assist chaperone machinery at the flagellar tip to
      actively convert the smaller spoke precursor and itself into the mature stable
      complex; failure of the interaction between the spoke HSP40 and its target
      polypeptide results in heterogeneous unstable radial spokes in pf24.

PMID- 15563612
TI  - Loss of function of KRE5 suppresses temperature sensitivity of mutants lacking
      mitochondrial anionic lipids.
AB  - Disruption of PGS1, which encodes the enzyme that catalyzes the committed step of
      cardiolipin (CL) synthesis, results in loss of the mitochondrial anionic
      phospholipids phosphatidylglycerol (PG) and CL. The pgs1Delta mutant exhibits
      severe growth defects at 37 degrees C. To understand the essential functions of
      mitochondrial anionic lipids at elevated temperatures, we isolated suppressors of
      pgs1Delta that grew at 37 degrees C. One of the suppressors has a loss of
      function mutation in KRE5, which is involved in cell wall biogenesis. The cell
      wall of pgs1Delta contained markedly reduced beta-1,3-glucan, which was restored
      in the suppressor. Stabilization of the cell wall with osmotic support alleviated
      the cell wall defects of pgs1Delta and suppressed the temperature sensitivity of
      all CL-deficient mutants. Evidence is presented suggesting that the previously
      reported inability of pgs1Delta to grow in the presence of ethidium bromide was
      due to defective cell wall integrity, not from "petite lethality." These findings
      demonstrated that mitochondrial anionic lipids are required for cellular
      functions that are essential in cell wall biogenesis, the maintenance of cell
      integrity, and survival at elevated temperature.

PMID- 15563614
TI  - Inactivation of the clpC1 gene encoding a chloroplast Hsp100 molecular chaperone
      causes growth retardation, leaf chlorosis, lower photosynthetic activity, and a
      specific reduction in photosystem content.
AB  - ClpC is a molecular chaperone of the Hsp100 family. In higher plants there are
      two chloroplast-localized paralogs (ClpC1 and ClpC2) that are approximately 93%
      similar in primary sequence. In this study, we have characterized two independent
      Arabidopsis (Arabidopsis thaliana) clpC1 T-DNA insertion mutants lacking on
      average 65% of total ClpC content. Both mutants display a retarded-growth
      phenotype, leaves with a homogenous chlorotic appearance throughout all
      developmental stages, and more perpendicular secondary influorescences.
      Photosynthetic performance was also impaired in both knockout lines, with
      relatively fewer photosystem I and photosystem II complexes, but no changes in
      ATPase and Rubisco content. However, despite the specific drop in photosystem I
      and photosystem II content, no changes in leaf cell anatomy or chloroplast
      ultrastructure were observed in the mutants compared to the wild type. Previously
      proposed functions for envelope-associated ClpC in chloroplast protein import and
      degradation of mistargeted precursors were examined and shown not to be
      significantly impaired in the clpC1 mutants. In the stroma, where the majority of
      ClpC protein is localized, marked increases of all ClpP paralogs were observed in
      the clpC1 mutants but less variation for the ClpR paralogs and a corresponding
      decrease in the other chloroplast-localized Hsp100 protein, ClpD. Increased
      amounts of other stromal molecular chaperones (Cpn60, Hsp70, and Hsp90) and
      several RNA-binding proteins were also observed. Our data suggest that overall
      ClpC as a stromal molecular chaperone plays a vital role in chloroplast function
      and leaf development and is likely involved in photosystem biogenesis.

PMID- 15563615
TI  - Differential expression on a daily basis of plastid sigma factor genes from the
      moss Physcomitrella patens. Regulatory interactions among PpSig5, the circadian
      clock, and blue light signaling mediated by cryptochromes.
AB  - The nuclear-encoded plastid sigma factors are supposed to be a regulatory subunit
      of the multisubunit bacteria-type plastid RNA polymerase. We studied here whether
      or not three genes, PpSig1, PpSig2, and PpSig5 encoding plastid sigma factors,
      are controlled by the circadian clock and/or by blue light signaling in the moss
      Physcomitrella patens. Among the three PpSig genes, only PpSig5 was clearly
      controlled by the circadian clock. In contrast to the differential regulation on
      a daily timescale, a pulse of blue light induced the expression of all the three
      PpSig genes. This induction was significantly reduced in a knockout mutant that
      lacked the blue light photoreceptor cryptochromes PpCRY1a and PpCRY1b, indicating
      that PpCRY1a and/or PpCRY1b mediate the blue light signal that induces the
      expression of the PpSig genes. In a daily cycle of 12-h blue light/12-h dark, the
      timing of peak expression of PpSig5 and a chloroplast gene psbD, encoding the D2
      subunit of photosystem II, advanced in the cryptochrome mutant relative to those
      in the wild type, suggesting the presence of regulatory interactions among the
      expression of PpSig5 and psbD, the circadian clock, and the blue light signaling
      mediated by the cryptochrome(s).

PMID- 15563616
TI  - The biosynthesis of UDP-galacturonic acid in plants. Functional cloning and
      characterization of Arabidopsis UDP-D-glucuronic acid 4-epimerase.
AB  - UDP-GlcA 4-epimerase (UGlcAE) catalyzes the epimerization of UDP-alpha-D
      glucuronic acid (UDP-GlcA) to UDP-alpha-D-galacturonic acid (UDP-GalA). UDP-GalA
      is a precursor for the synthesis of numerous cell-surface polysaccharides in
      bacteria and plants. Using a biochemical screen, a gene encoding AtUGlcAE1 in
      Arabidopsis (Arabidopsis thaliana) was identified and the recombinant enzyme
      biochemically characterized. The gene belongs to a small gene family composed of
      six isoforms. All members of the UGlcAE gene family encode a putative type-II
      membrane protein and have two domains: a variable N-terminal region approximately
      120 amino acids long composed of a predicted cytosolic, transmembrane, and stem
      domain, followed by a large conserved C-terminal catalytic region approximately
      300 amino acids long composed of a highly conserved catalytic domain found in a
      large protein family of epimerase/dehydratases. The recombinant epimerase has a
      predicted molecular mass of approximately 43 kD, although size-exclusion
      chromatography suggests that it may exist as a dimer (approximately 88 kD).
      AtUGlcAE1 forms UDP-GalA with an equilibrium constant value of approximately 1.9
      and has an apparent K(m) value of 720 microm for UDP-GlcA. The enzyme has maximum
      activity at pH 7.5 and is active between 20 degrees C and 55 degrees C.
      Arabidopsis AtUGlcAE1 is not inhibited by UDP-Glc, UDP-Gal, or UMP. However, the
      enzyme is inhibited by UDP-Xyl and UDP-Ara, suggesting that these nucleotide
      sugars have a role in regulating the synthesis of pectin. The cloning of the
      AtUGlcAE1 gene will increase our ability to investigate the molecular factors
      that regulate pectin biosynthesis in plants. The availability of a functional
      recombinant UDP-GlcA 4-epimerase will be of considerable value for the facile
      generation of UDP-d-GalA in the amounts required for detailed studies of pectin
      biosynthesis.

PMID- 15563617
TI  - The role of plastocyanin in the adjustment of the photosynthetic electron
      transport to the carbon metabolism in tobacco.
AB  - We investigated adaptive responses of the photosynthetic electron transport to a
      decline in the carbon assimilation capacity. Leaves of different ages from wild
      type tobacco (Nicotiana tabacum) L. var Samsun NN and young mature leaves of
      tobacco transformants with impaired photoassimilate export were used. The
      assimilation rate decreased from 280 in young mature wild-type leaves to below 50
      mmol electrons mol chlorophyll(-1) s(-1) in older wild-type leaves or in
      transformants. The electron transport capacity, measured in thylakoids isolated
      from the different leaves, closely matched the leaf assimilation rate. The
      numbers of cytochrome (cyt)-bf complexes and plastocyanin (PC) decreased with the
      electron transport and assimilation capacity, while the numbers of photosystem I
      (PSI), photosystem II, and plastoquinone remained constant. The PC to PSI ratio
      decreased from five in leaves with high assimilation rates, to values below one
      in leaves with low assimilation rates, and the PC versus flux correlation was
      strictly proportional. Redox kinetics of cyt-f, PC, and P700 suggest that in
      leaves with low electron fluxes, PC is out of the equilibrium with P700 and cyt-f
      and the cyt-f reoxidation rate is restricted. It is concluded that the electron
      flux is sensitive to variations in the number of PC, relative to PSI and cyt-bf,
      and PC, in concert with cyt-bf, is a key component that adjusts to control the
      electron transport rate. PC dependent flux control may serve to adjust the
      electron transport rate under conditions where the carbon assimilation is
      diminished and thereby protects PSI against over-reduction and reactive oxygen
      production.

PMID- 15563618
TI  - Green fluorescent protein-mTalin causes defects in actin organization and cell
      expansion in Arabidopsis and inhibits actin depolymerizing factor's actin
      depolymerizing activity in vitro.
AB  - Expression of green fluorescent protein (GFP) linked to an actin binding domain
      is a commonly used method for live cell imaging of the actin cytoskeleton. One of
      these chimeric proteins is GFP-mTalin (GFP fused to the actin binding domain of
      mouse talin). Although it has been demonstrated that GFP-mTalin colocalizes with
      the actin cytoskeleton, its effect on actin dynamics and cell expansion has not
      been studied in detail. We created Arabidopsis (Arabidopsis thaliana) plants
      harboring alcohol inducible GFP-mTalin constructs to assess the effect of GFP
      mTalin expression in vivo. We focused on the growing root hair as this is a model
      cell for studying cell expansion and root hair tip growth that requires a highly
      dynamic and polar actin cytoskeleton. We show that alcohol inducible expression
      of GFP-mTalin in root hairs causes severe defects in actin organization,
      resulting in either the termination of growth, cell death, and/or changes in cell
      shape. Fluorescence recovery after photobleaching experiments demonstrate that
      the interaction of GFP-mTalin and actin filaments is highly dynamic. To assess
      how GFP-mTalin affects actin dynamics we performed cosedimentation assays of GFP
      mTalin with actin on its own or in the presence of the actin modulating protein,
      actin depolymerizing factor. We show that that GFP-mTalin does not affect actin
      polymerization but that it does inhibit the actin depolymerizing activity of
      actin depolymerizing factor. These observations demonstrate that GFP-mTalin can
      affect cell expansion, actin organization, and the interaction of actin binding
      proteins with actin.

PMID- 15563619
TI  - Nitric oxide block of outward-rectifying K+ channels indicates direct control by
      protein nitrosylation in guard cells.
AB  - Recent work has indicated that nitric oxide (NO) and its synthesis are important
      elements of signal cascades in plant pathogen defense and are a prerequisite for
      drought and abscisic acid responses in Arabidopsis (Arabidopsis thaliana) and
      Vicia faba guard cells. Nonetheless, its mechanism(s) of action has not been well
      defined. NO regulates inward-rectifying K+ channels of Vicia guard cells through
      its action on Ca2+ release from intercellular Ca2+ stores, but alternative
      pathways are indicated for its action on the outward-rectifying K+ channels
      (I(K,out)), which are Ca2+ insensitive. We report here that NO affects I(K,out)
      when NO is elevated above approximately 10 to 20 nm. NO action on I(K,out) was
      consistent with oxidative stress and was suppressed by several reducing agents,
      the most effective being British anti-Lewisite (2,3-dimercapto-1-propanol). The
      effect of NO on the K+ channel was mimicked by phenylarsine oxide, an oxidizing
      agent that cross-links vicinal thiols. Neither intracellular pH buffering nor the
      phosphotyrosine kinase antagonist genistein affected NO action on I(K,out),
      indicating that changes in cytosolic pH and tyrosine phosphorylation are unlikely
      to contribute to NO or phenylarsine oxide action in this instance. Instead, our
      results strongly suggest that NO directly modifies the K+ channel or a closely
      associated regulatory protein, probably by nitrosylation of cysteine sulfhydryl
      groups.

PMID- 15563620
TI  - Metabolic engineering of the chloroplast genome using the Echerichia coli ubiC
      gene reveals that chorismate is a readily abundant plant precursor for p
      hydroxybenzoic acid biosynthesis.
AB  - p-Hydroxybenzoic acid (pHBA) is the major monomer in liquid crystal polymers. In
      this study, the Escherichia coli ubiC gene that codes for chorismate pyruvate
      lyase (CPL) was integrated into the tobacco (Nicotiana tabacum) chloroplast
      genome under the control of the light-regulated psbA 5' untranslated region. CPL
      catalyzes the direct conversion of chorismate, an important branch point
      intermediate in the shikimate pathway that is exclusively synthesized in
      plastids, to pHBA and pyruvate. The leaf content of pHBA glucose conjugates in
      fully mature T1 plants exposed to continuous light (total pooled material) varied
      between 13% and 18% dry weight, while the oldest leaves had levels as high as
      26.5% dry weight. The latter value is 50-fold higher than the best value reported
      for nuclear-transformed tobacco plants expressing a chloroplast-targeted version
      of CPL. Despite the massive diversion of chorismate to pHBA, the plastid
      transformed plants and control plants were indistinguishable. The highest CPL
      enzyme activity in pooled leaf material from adult T1 plants was 50,783 pkat/mg
      of protein, which is equivalent to approximately 35% of the total soluble protein
      and approximately 250 times higher than the highest reported value for nuclear
      transformation. These experiments demonstrate that the current limitation for
      pHBA production in nuclear-transformed plants is CPL enzyme activity, and that
      the process becomes substrate-limited only when the enzyme is present at very
      high levels in the compartment of interest, such as the case with plastid
      transformation. Integration of CPL into the chloroplast genome provides a
      dramatic demonstration of the high-flux potential of the shikimate pathway for
      chorismate biosynthesis, and could prove to be a cost-effective route to pHBA.
      Moreover, exploiting this strategy to create an artificial metabolic sink for
      chorismate could provide new insight on regulation of the plant shikimate pathway
      and its complex interactions with downstream branches of secondary metabolism,
      which is currently poorly understood.

PMID- 15563621
TI  - Nuclear SDH2-1 and SDH2-2 genes, encoding the iron-sulfur subunit of
      mitochondrial complex II in Arabidopsis, have distinct cell-specific expression
      patterns and promoter activities.
AB  - Three different nuclear genes encode the essential iron-sulfur subunit of
      mitochondrial complex II (succinate dehydrogenase) in Arabidopsis (Arabidopsis
      thaliana), raising interesting questions about their origin and function. To find
      clues about their role, we have undertaken a detailed analysis of their
      expression. Two genes (SDH2-1 and SDH2-2) that likely arose via a relatively
      recent duplication event are expressed in all organs from adult plants, whereas
      transcripts from the third gene (SDH2-3) were not detected. The tissue- and cell
      specific expression of SDH2-1 and SDH2-2 was investigated by in situ
      hybridization. In flowers, both genes are regulated in a similar way. Enhanced
      expression was observed in floral meristems and sex organ primordia at early
      stages of development. As flowers develop, SDH2-1 and SDH2-2 transcripts
      accumulate in anthers, particularly in the tapetum, pollen mother cells, and
      microspores, in agreement with an essential role of mitochondria during anther
      development. Interestingly, in contrast to the situation in flowers, only SDH2-2
      appears to be expressed at a significant level in root tips. Strong labeling was
      observed in all cell layers of the root meristematic zone, and a cell-specific
      pattern of expression was found with increasing distance from the root tip, as
      cells attain their differentiated state. Analysis of transgenic Arabidopsis
      plants carrying SDH2-1 and SDH2-2 promoters fused to the beta-glucuronidase
      reporter gene indicate that both promoters have similar activities in flowers,
      driving enhanced expression in anthers and/or pollen, and that only the SDH2-2
      promoter is active in root tips. These beta-glucuronidase staining patterns
      parallel those obtained by in situ hybridization, suggesting transcriptional
      regulation of these genes. Progressive deletions of the promoters identified
      regions important for SDH2-1 expression in anthers and/or pollen and for SDH2-2
      expression in anthers and/or pollen and root tips. Interestingly, regions driving
      enhanced expression in anthers are differently located in the two promoters.

PMID- 15563622
TI  - Phenolic profiling of caffeic acid O-methyltransferase-deficient poplar reveals
      novel benzodioxane oligolignols.
AB  - Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation
      of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we
      have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem
      tissue from COMT-deficient and control poplars (Populus spp.), using statistical
      analysis of the peak heights. COMT down-regulation results in significant
      concentration differences for 25 of the 91 analyzed peaks. Eight peaks were
      exclusively detected in COMT-deficient poplar, of which four could be purified
      for further identification using mass spectrometry/mass spectrometry, nuclear
      magnetic resonance, and spiking of synthesized reference compounds. These new
      compounds were derived from 5-hydroxyconiferyl alcohol or 5
      hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a
      structural type that is also increased in the lignins of COMT-deficient plants.
      One of these four benzodioxanes amounted to the most abundant oligolignol in the
      HPLC profile. Furthermore, all of the differentially accumulating oligolignols
      involving sinapyl units were either reduced in abundance or undetectable. The
      concentration levels of all identified oligolignols were in agreement with the
      relative supply of monolignols and with their chemical coupling propensities,
      which supports the random coupling hypothesis. Chiral HPLC analysis of the most
      abundant benzodioxane dimer revealed the presence of both enantiomers in equal
      amounts, indicating that they were formed by radical coupling reactions under
      simple chemical control rather than guided by dirigent proteins.

PMID- 15563623
TI  - Glutamate dehydrogenase of tobacco is mainly induced in the cytosol of phloem
      companion cells when ammonia is provided either externally or released during
      photorespiration.
AB  - Glutamate (Glu) dehydrogenase (GDH) catalyses the reversible amination of 2
      oxoglutarate for the synthesis of Glu using ammonium as a substrate. This enzyme
      preferentially occurs in the mitochondria of companion cells of a number of plant
      species grown on nitrate as the sole nitrogen source. For a better understanding
      of the controversial role of GDH either in ammonium assimilation or in the supply
      of 2-oxoglutarate (F. Dubois, T. Terce-Laforgue, M.B. Gonzalez-Moro, M.B.
      Estavillo, R. Sangwan, A. Gallais, B. Hirel [2003] Plant Physiol Biochem 41: 565
      576), we studied the localization of GDH in untransformed tobacco (Nicotiana
      tabacum) plants grown either on low nitrate or on ammonium and in ferredoxin
      dependent Glu synthase antisense plants. Production of GDH and its activity were
      strongly induced when plants were grown on ammonium as the sole nitrogen source.
      The induction mainly occurred in highly vascularized organs such as stems and
      midribs and was likely to be due to accumulation of phloem-translocated ammonium
      in the sap. GDH induction occurred when ammonia was applied externally to
      untransformed control plants or resulted from photorespiratory activity in
      transgenic plants down-regulated for ferredoxin-dependent Glu synthase. GDH was
      increased in the mitochondria and appeared in the cytosol of companion cells.
      Taken together, our results suggest that the enzyme plays a dual role in
      companion cells, either in the mitochondria when mineral nitrogen availability is
      low or in the cytosol when ammonium concentration increases above a certain
      threshold.

PMID- 15563624
TI  - Short-day potentiation of low temperature-induced gene expression of a C-repeat
      binding factor-controlled gene during cold acclimation in silver birch.
AB  - Development of winter hardiness in trees is a two-stage process involving
      sequential perception of distinct environmental cues, short-day (SD) photoperiod
      and low temperature (LT). We have shown that both SD and LT are recognized by
      leaves of silver birch (Betula pendula cv Roth) leading to increased freezing
      tolerance, and thus leaves can be used as an experimental model to study the
      physiological and molecular events taking place during cold acclimation. To
      obtain a molecular marker for the acclimation process in birch we cloned a gene,
      designated Bplti36, encoding a 36-kD acidic SK2 type of dehydrin. The gene was
      responsive to LT, drought, salt, and exogenous abscisic acid. This responsiveness
      to abiotic stresses and abscisic acid was retained when Bplti36 was introduced to
      Arabidopsis (Arabidopsis thaliana). The LT induction of the gene appeared to be
      under the control of the C-repeat-binding factor pathway as suggested by the
      presence of several C-repeat/dehydration-responsive element/LT-responsive
      elements in the Bplti36 promoter and its constitutive expression in C-repeat
      binding factor overproducing Arabidopsis. In birch SD photoperiod at normal
      growth temperature did not result in significant induction of Bplti36. However,
      preexposure to SD followed by LT treatment resulted in a remarkable increase in
      Bplti36 transcript accumulation as compared to LT-treated plants grown at long
      day photoperiod. This suggests that SD photoperiod potentiates the LT response by
      conditioning the leaf tissue to be more responsive to the LT stimulus.

PMID- 15563625
TI  - Characterization of anion channels in the plasma membrane of Arabidopsis
      epidermal root cells and the identification of a citrate-permeable channel
      induced by phosphate starvation.
AB  - Organic-acid secretion from higher plant roots into the rhizosphere plays an
      important role in nutrient acquisition and metal detoxification. In this study we
      report the electrophysiological characterization of anion channels in Arabidopsis
      (Arabidopsis thaliana) root epidermal cells and show that anion channels
      represent a pathway for citrate efflux to the soil solution. Plants were grown in
      nutrient-replete conditions and the patch clamp technique was applied to
      protoplasts isolated from the root epidermal cells of the elongation zone and
      young root hairs. Using SO4(2-) as the dominant anion in the pipette, voltage
      dependent whole-cell inward currents were activated at membrane potentials
      positive of -180 mV exhibiting a maximum peak inward current (I(peak)) at
      approximately -130 mV. These currents reversed at potentials close to the
      equilibrium potential for SO4(2-), indicating that the inward currents
      represented SO4(2-) efflux. Replacing intracellular SO4(2-) with Cl- or NO3(-)
      resulted in inward currents exhibiting similar properties to the SO4(2-) efflux
      currents, suggesting that these channels were also permeable to a range of
      inorganic anions; however when intracellular SO4(2-) was replaced with citrate or
      malate, no inward currents were ever observed. Outside-out patches were used to
      characterize a 12.4-picoSiemens channel responsible for these whole-cell
      currents. Citrate efflux from Arabidopsis roots is induced by phosphate
      starvation. Thus, we investigated anion channel activity from root epidermal
      protoplasts isolated from Arabidopsis plants deprived of phosphate for up to 7 d
      after being grown for 10 d on phosphate-replete media (1.25 mm). In contrast to
      phosphate-replete plants, protoplasts from phosphate-starved roots exhibited
      depolarization-activated voltage-dependent citrate and malate efflux currents.
      Furthermore, phosphate starvation did not regulate inorganic anion efflux,
      suggesting that citrate efflux is probably mediated by novel anion channel
      activity, which could have a role in phosphate acquisition.

PMID- 15563626
TI  - Inhibition of blue light-dependent H+ pumping by abscisic acid through hydrogen
      peroxide-induced dephosphorylation of the plasma membrane H+-ATPase in guard cell
      protoplasts.
AB  - Blue light (BL)-dependent H+ pumping by guard cells, which drives stomatal
      opening, is inhibited by abscisic acid (ABA). We investigated this response with
      respect to the activity of plasma membrane H+-ATPase using Vicia guard cell
      protoplasts. ATP hydrolysis by the plasma membrane H+-ATPase, phosphorylation of
      the H+-ATPase, and the binding of 14-3-3 protein to the H+-ATPase stimulated by
      BL were inhibited by ABA at 10 microm. All of these responses were similarly
      inhibited by hydrogen peroxide (H2O2) at 1 mm. The ABA-induced inhibitions of BL
      dependent H+ pumping and phosphorylation of the H+-ATPase were partially restored
      by ascorbate, an intracellular H2O2 scavenger. A single-cell analysis of the
      cytosolic H2O2 using 2',7'-dichlorofluorescin revealed that H2O2 was generated by
      ABA in guard cell protoplasts. We also indicated that H+ pumping induced by
      fusicoccin and the binding of 14-3-3 protein to the H+-ATPase were inhibited
      slightly (approximately 20%) by both ABA and H2O2. By contrast, H2O2 at 1 mm did
      not affect H+ pumping by the H+-ATPase in microsomal membranes. From these
      results, we concluded that inhibition of BL-dependent H+ pumping by ABA was due
      to a decrease in the phosphorylation levels of H+-ATPase and that H2O2 might be
      involved in this response. Moreover, there are at least two inhibition sites by
      ABA in the BL signaling pathway of guard cells.

PMID- 15563627
TI  - Effect of the Colorless non-ripening mutation on cell wall biochemistry and gene
      expression during tomato fruit development and ripening.
AB  - The Colorless non-ripening (Cnr) mutation in tomato (Solanum lycopersicum)
      results in mature fruits with colorless pericarp tissue showing an excessive loss
      of cell adhesion (A.J. Thompson, M. Tor, C.S. Barry, J. Vrebalov, C. Orfila, M.C.
      Jarvis, J.J. Giovannoni, D. Grierson, G.B. Seymour [1999] Plant Physiol 120: 383
      390). This pleiotropic mutation is an important tool for investigating the
      biochemical and molecular basis of cell separation during ripening. This study
      reports on the changes in enzyme activity associated with cell wall disassembly
      in Cnr and the effect of the mutation on the program of ripening-related gene
      expression. Real-time PCR and biochemical analysis demonstrated that the
      expression and activity of a range of cell wall-degrading enzymes was altered in
      Cnr during both development and ripening. These enzymes included
      polygalacturonase, pectinesterase (PE), galactanase, and xyloglucan
      endotransglycosylase. In the case of PE, the protein product of the ripening
      related isoform PE2 was not detected in the mutant. In contrast with wild type,
      Cnr fruits were rich in basic chitinase and peroxidase activity. A microarray and
      differential screen were used to profile the pattern of gene expression in wild
      type and Cnr fruits. They revealed a picture of the gene expression in the mutant
      that was largely consistent with the real-time PCR and biochemical experiments.
      Additionally, these experiments demonstrated that the Cnr mutation had a profound
      effect on many aspects of ripening-related gene expression. This included a
      severe reduction in the expression of ripening-related genes in mature fruits and
      indications of premature expression of some of these genes in immature fruits.
      The program of gene expression in Cnr resembles to some degree that found in
      dehiscence or abscission zones. We speculate that there is a link between events
      controlling cell separation in tomato, a fleshy fruit, and those involved in the
      formation of dehiscence zones in dry fruits.

PMID- 15563628
TI  - Incidence of associated events during the performance of invasive procedures in
      healthy human volunteers.
AB  - Metabolic investigations often utilize arteriovenous sampling and muscle biopsy.
      These investigations represent some risk to the subject. We examined 369 studies
      performed in the General Clinical Research Center between January 1994 and May
      2003 for events related to femoral catheterization and muscle biopsies. Incidents
      were further examined by age (younger: 18-59 yr, n=133; and older: 60-76 yr,
      n=28). There were no clinically defined major complications associated with
      either procedure. The incidence of femoral catheter repositioning or reinsertion
      was higher in the older group (25.5 vs. 9.7%). There was no difference in the
      incidence of premature removal of catheters, ecchymosis or hematoma, or the
      persistence of pain after discharge. The occurrence of all incidents did not
      increase with multiple catheterizations. Muscle biopsy was associated with
      infrequent ecchymosis or hematoma in both groups (1.1 and 3.6% in younger and
      older groups, respectively). Both procedures entail a small likelihood of a
      vagallike response (3.3% overall), resulting in nausea, dizziness, and rarely a
      loss of consciousness. These results indicate that, in skilled hands and a
      defined clinical setting, the incidents associated with femoral catheterization
      and muscle biopsy in healthy volunteers are reasonable and largely controllable.

PMID- 15563629
TI  - Effects of body weight-supported treadmill training on heart rate variability and
      blood pressure variability in individuals with spinal cord injury.
AB  - Individuals with spinal cord injury are prone to cardiovascular dysfunction and
      an increased risk of cardiovascular disease. Body weight-supported treadmill
      training (BWSTT) may enhance ambulation in individuals with incomplete spinal
      cord injury; however, its effects on cardiovascular regulation have not been
      investigated. The purpose of this study was to examine the effects of 6-mo of
      BWSTT on the autonomic regulation of heart rate (HR) and blood pressure (BP) in
      individuals with incomplete tetraplegia. Eight individuals [age 27.6 yr (SD 5.2)]
      with spinal cord injury [C4-C5; American Spinal Injury Association B-C; 9.6 yr
      (SD 7.5) postinjury] participated. Ten-minute HR and finger arterial pressure
      (Finapres) recordings were collected during 1) supine rest and 2) an orthostatic
      stress (60 degrees head-up tilt) before and after 6 mo of BWSTT. Frequency domain
      measures of HR variability [low-frequency (LF) power, high-frequency (HF) power,
      and LF-to-HF ratio] and BP variability (systolic and diastolic LF power) were
      used as clinically valuable indexes of neurocardiac and neurovascular control,
      respectively. There was a significant reduction in HR [61.9 (SD 6.9) vs. 55.7
      beats/min (SD 7.7); P=0.05] and LF-to-HF ratio [1.23 (SD 0.47) vs. 0.99 (SD
      0.40); P < 0.05] after BWSTT. There was a significant reduction in LF systolic BP
      [183.1 (SD 46.8) vs. 158.4 mmHg2 (SD 45.2); P < 0.01] but no change in BP. There
      were no significant effects of training on HR variability or BP variability
      during 60 degrees head-up tilt. In conclusion, individuals with incomplete
      tetraplegia retain the ability to make positive changes in cardiovascular
      autonomic regulation with BWSTT without worsening orthostatic intolerance.

PMID- 15563630
TI  - Agonist-dependent variablity of contributions of nitric oxide and prostaglandins
      in human skeletal muscle.
AB  - The relative contributions of endothelium-dependent dilators [nitric oxide (NO),
      prostaglandins (PGs), and endothelium-derived hyperpolarizing factor (EDHF)] in
      human limbs are poorly understood. We tested the hypothesis that relative
      contributions of NO and PGs differ between endothelial agonists acetylcholine
      (ACh; 1, 2, and 4 microg.dl(-1).min(-1)) and bradykinin (BK; 6.25, 25, and 50
      ng.dl(-1).min(-1)). We measured forearm blood flow (FBF) using venous occlusion
      plethysmography in 50 healthy volunteers (27 +/- 1 yr) in response to brachial
      artery infusion of ACh or BK in the absence and presence of inhibitors of NO
      synthase [NOS; with NG-monomethyl-L-arginine (L-NMMA)] and cyclooxygenase (COX;
      with ketorolac). Furthermore, we tested the idea that the NOS + COX-independent
      dilation (in the presence of L-NMMA + ketorolac, presumably EDHF) could be
      inhibited by exogenous NO administration, as reported in animal studies. FBF
      increased approximately 10-fold in the ACh control; L-NMMA reduced baseline FBF
      and ACh dilation, whereas addition of ketorolac had no further effect. Ketorolac
      alone did not alter ACh dilation, but addition of L-NMMA reduced ACh dilation
      significantly. For BK infusion, FBF increased approximately 10-fold in the
      control condition; L-NMMA tended to reduce BK dilation (P < 0.1), and addition of
      ketorolac significantly reduced BK dilation. Similar to ACh, ketorolac alone did
      not alter BK dilation, but addition of L-NMMA reduced BK dilation. To test the
      idea that NO can inhibit the NOS + COX-independent portion of dilation, we
      infused a dose of sodium nitroprusside (NO-clamp technique) during ACh or BK that
      restored the reduction in baseline blood flow due to L-NMMA. Regardless of
      treatment order, the NO clamp restored baseline FBF but did not reduce the NOS +
      COX-independent dilation to ACh or BK. We conclude that the contribution of NO
      and PGs differs between ACh and BK, with ACh being more dependent on NO and BK
      being mostly dependent on a NOS + COX-independent mechanism (EDHF) in healthy
      young adults. The NOS + COX-independent dilation does not appear sensitive to
      feedback inhibition from NO in the human forearm.

PMID- 15563631
TI  - An animal model of autoimmune emphysema.
AB  - Although cigarette smoking is implicated in the pathogenesis of emphysema, the
      precise mechanisms of chronic progressive alveolar septal destruction are not
      well understood. We show, in a novel animal model, that immunocompetent, but not
      athymic, nude rats injected intraperitoneally with xenogeneic endothelial cells
      (ECs) produce antibodies against ECs and develop emphysema. Immunization with ECs
      also leads to alveolar septal cell apoptosis and activation of matrix
      metalloproteases MMP-9 and MMP-2. Anti-EC antibodies cause EC apoptosis in vitro
      and emphysema in passively immunized mice. Moreover, immunization also causes
      accumulation of CD4+ T cells in the lung. Adoptive transfer of pathogenic, spleen
      derived CD4+ cells into naive immunocompetent animal also results in emphysema.
      This study shows for the first time that humoral- and CD4+ cell-dependent
      mechanisms are sufficient to trigger the development of emphysema, suggesting
      that alveolar septal cell destruction might result from immune mechanisms.

PMID- 15563632
TI  - Incidence of and risk factors for pulmonary complications after nonthoracic
      surgery.
AB  - The prediction of postoperative pulmonary complications is an underinvestigated
      field. We conducted a prospective cohort study (with postoperative pulmonary
      complications ascertained by an investigator blinded to perioperative variables)
      to determine the risk factors for pulmonary complications after elective
      nonthoracic surgery. Of 1,055 consecutive patients attending the Pre-Admission
      Clinic of a university hospital (mean age 55 years, 50% men, 15% with history of
      obstructive airways disease), 28 (2.7%) suffered a postoperative pulmonary
      complication within 7 days of surgery: 13 patients developed respiratory failure
      requiring ventilatory support, 9 pneumonia, 5 atelectasis requiring bronchoscopic
      intervention, and 1 pneumothorax requiring intervention. Mean lengths of stay
      were substantially prolonged for those patients who developed pulmonary
      complications within 7 days of surgery: 27.9 days versus 4.5 days, p = 0.006.
      Eight variables were statistically significantly associated with pulmonary
      complications on bivariate analyses. Multivariate analyses revealed that four
      were independently associated with increased risk of pulmonary complications: age
      (odds ratio [OR] 5.9 for age >/= 65 years, p < 0.001), positive cough test (OR
      3.8, P = 0.01), perioperative nasogastric tube (OR 7.7, p < 0.001), and duration
      of anesthesia (OR 3.3 for operations lasting at least 2.5 hours, p = 0.008).
      Thus, several perioperative factors predict an increased risk for pulmonary
      complications after elective nonthoracic surgery.

PMID- 15563633
TI  - Relationship of small airway chymase-positive mast cells and lung function in
      severe asthma.
AB  - Distal lung inflammation may be important in asthma pathophysiology. The goal of
      this study was to measure cellular inflammation in the large airway and four
      distal lung regions (small airway inner and outer wall, alveolar attachments, and
      peripheral alveolar tissue) and to correlate the specific inflammatory cells with
      several lung function parameters. Sections of concurrently obtained endobronchial
      and transbronchial/surgical biopsy tissue from 20 individuals with severe asthma
      were immunostained for T-lymphocyte, eosinophil, monocyte/macrophage, neutrophil,
      and two mast cell markers (tryptase and chymase). Specific cell distributions
      were determined and correlated with lung function measures. The number of
      inflammatory cells generally increased toward the periphery, but the percentage
      of T-lymphocytes, eosinophils, monocytes/macrophages, and neutrophils remained
      similar or decreased from large to small airways. In contrast, mast cell number,
      percentage, and the chymase-positive phenotype increased in small airway regions.
      After the analysis was adjusted for multiple comparisons, only chymase-positive
      mast cells significantly and positively correlated with lung function. Such a
      relationship was seen only in the small airway/alveolar attachments lung region
      (r(s) = 0.61-0.89; p </= 0.001 for all correlations). These data suggest that
      induction of chymase-positive mast cells, particularly in the small airway outer
      wall/alveolar attachments region, may be protective for lung function in severe
      asthma.

PMID- 15563634
TI  - On the role of surface tension in the pathophysiology of emphysema.

PMID- 15563635
TI  - Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat
      pulmonary hypertension.
AB  - We have found in chronically hypoxic rats that acute intravenous administration
      of the Rho kinase inhibitor Y-27632 nearly normalizes the pulmonary hypertension
      (PH) but has no pulmonary vascular selectivity. In this study, we tested if oral
      or inhaled Y-27632 would be an effective and selective pulmonary vasodilator in
      hypoxic PH. Although acute oral Y-27632 caused a marked and sustained decrease in
      mean pulmonary arterial pressure (MPAP), it also decreased mean systemic arterial
      pressure (MSAP). In contrast, 5 minutes of inhaled Y-27632 decreased MPAP without
      reducing MSAP. The hypotensive effect of inhaled Y-27632 on hypoxic PH was
      greater than that of inhaled nitric oxide, and the effect lasted for at least 5
      hours. Inhaled fasudil, another Rho kinase inhibitor, caused selective MPAP
      reductions in monocrotaline-induced PH and in spontaneous PH in fawn-hooded rats,
      as well as in chronically hypoxic rats. These results suggested that inhaled Y
      27632 was more effective than inhaled nitric oxide as a selective pulmonary
      vasodilator in hypoxic PH, and that Rho kinase-mediated vasoconstriction was also
      involved in the other models of PH. Inhaled Rho kinase inhibitors might be useful
      for acute vasodilator testing in patients with PH, and future work should
      evaluate their efficacy in the long-term treatment of PH.

PMID- 15563636
TI  - Progressive transforming growth factor beta1-induced lung fibrosis is blocked by
      an orally active ALK5 kinase inhibitor.
AB  - Pulmonary fibrosis is characterized by chronic scar formation and deposition of
      extracellular matrix, resulting in impaired lung function and respiratory
      failure. Idiopathic pulmonary fibrosis (IPF) is associated with pronounced
      morbidity and mortality and responds poorly to known therapeutic interventions;
      there are no known drugs that effectively block or reverse progressive fibrosis.
      Transforming growth factor beta (TGF-beta) is known to mediate extracellular
      matrix gene regulation and appears to be a major player in both the initiation
      and progression of IPF. TGF-beta mediates its biological effects through members
      of a family of activin receptor-like kinases (ALK). We have used a gene transfer
      model of progressive TGF-beta1-induced pulmonary fibrosis in rats to study a
      newly described orally active small molecular weight drug that is a potent and
      selective inhibitor of the kinase activity of ALK5, the specific TGF-beta
      receptor. We show that the drug inhibits the induction of fibrosis when
      administered at the time of initiation of fibrogenesis and, most important,
      blocks progressive fibrosis when administered transiently to animals with
      established fibrosis. These data show promise of the development of an effective
      therapeutic intervention for IPF and that inhibition of chronic progressive
      fibrosis may be achieved by blocking TGF-beta receptor activation.

PMID- 15563637
TI  - Arbitrary-pressure continuous positive airway pressure for obstructive sleep
      apnea syndrome.
AB  - Current resources are inadequate to meet the demand for polysomnography,
      resulting in long waiting lists. This study aimed to evaluate the role of
      arbitrary-pressure continuous positive airway pressure (CPAP) as a method to
      reduce delays in commencing treatment. The study was of an open, randomized,
      parallel design. Ninety-one subjects with obstructive sleep apnea syndrome were
      randomized to either arbitrary-pressure CPAP based on body mass index before
      treatment polysomnography or to CPAP at settings determined by polysomnography.
      Both interventions resulted in similar improvements in clinical outcomes as
      determined by Epworth Sleepiness Score, Short Form-36 Quality of Life
      questionnaire, objective compliance, and subjective attitudes to treatment. There
      was higher sleep efficiency at treatment polysomnography in the group commenced
      at arbitrary pressure (81.8 +/- 10.1% [mean +/- SD] compared with 72.2 +/- 18.0%,
      p = 0.01). Subjects unable to tolerate CPAP were identified by the use of
      arbitrary pressure, leading to a reduction in the proportion of "wasted"
      treatment polysomnograms (studies performed in subjects not persisting with
      treatment) relative to commencing therapy after treatment polysomnography (3 of
      39 compared with 12 of 35, p = 0.01). This approach to initiating treatment with
      CPAP appears feasible when there are long waiting lists for polysomnography.

PMID- 15563638
TI  - Ventilator-induced diaphragmatic dysfunction: toward a better treatment?

PMID- 15563639
TI  - Respiratory viral infections in high-risk patients.

PMID- 15563640
TI  - Reducing the cost of treating obstructive sleep apnea: good news for patients.

PMID- 15563641
TI  - Evidence-based colloid use in the critically ill: American Thoracic Society
      Consensus Statement.

PMID- 15563643
TI  - Linkage to apnea-hypopnea index across the life-span: is this a viable strategy?

PMID- 15563645
TI  - Urban health: a look out our windows.
AB  - Approximately 80% of Americans live in cities or immediately adjacent
      communities. Such urban environments are complex amalgams of people of disparate
      backgrounds, economic status, and expectations, with extraordinary disparities in
      health status and outcomes between groups just blocks apart. Urban health as a
      framing paradigm is of recent vintage and offers a perspective on health and
      disease that integrates clinical medicine and public health and draws on the
      social and political sciences to seek understanding of the impact of cities on
      the health of populations and individuals. Ironically, disparate outcomes and
      increased mortality among poor minority populations in cities are not primarily
      related to the consequences of the urban epidemics of drugs and violence but
      rather are due to the increased prevalence and severity of common diseases such
      as asthma, cardiovascular disease, diabetes, and kidney disease. Several factors
      may be responsible for such disparities, including stress, racism, perceptions of
      deprivation, economic inequalities, and lack of access to quality health care. It
      is time for leaders in medical education and health care delivery to focus on the
      populations that surround their institutions in order to study urban health and
      meet the challenge of caring for all the residents of our cities.

PMID- 15563646
TI  - Cities and health: history, approaches, and key questions.
AB  - The majority of the world's population will live in cities in the next few years,
      and the pace of urbanization worldwide will continue to accelerate over the
      coming decades. Such a dramatic demographic shift can be expected to have an
      impact on population health. Although there has been historic interest in how
      city living is associated with health, this interest has waxed and waned and a
      cogent framework has yet to evolve that encompasses key issues in urban health.
      In this article, the authors discuss three alternate approaches to the study of
      urban health today; these include considering urban health from the perspective
      of a presumed urban health penalty, from an urban sprawl perspective, and more
      comprehensively, considering how urban living conditions may be associated with
      health. The authors also propose three key questions that may help guide the
      study and practice of urban health in coming decades. These include considering
      what specific features of cities are causally related to health, the extent to
      which these features are unique to a particular city or are different between
      cities, and ultimately, to what extent these features of cities are modifiable in
      order to allow interventions that can improve the health of urban populations.

PMID- 15563647
TI  - Health disparities based on socioeconomic inequities: implications for urban
      health care.
AB  - Health is unevenly distributed across socioeconomic status. Persons of lower
      income, education, or occupational status experience worse health and die earlier
      than do their better-off counterparts. This article discusses these disparities
      in the context of urban medical practice. The article begins with a discussion of
      the complex relationship among socioeconomic status, race, and health in the
      United States. It highlights the effects of institutional, individual, and
      internalized racism on the health of African Americans, including the insidious
      consequences of residential segregation and concentrated poverty. Next, the
      article reviews health disparities based on socioeconomic status across the life
      cycle, beginning in fetal health and ending with disparities among the elderly.
      Potential explanations for these socioeconomic-based disparities are addressed,
      including reverse causality (e.g., being poor causes lower socioeconomic status)
      and confounding by genetic factors. The article underscores social causation as
      the primary explanation for health disparities and highlights the cumulative
      effects of social disadvantage across stages of the life cycle and across
      environments (e.g., fetal, family, educational, occupational, and neighborhood).
      The article concludes with a discussion of the implications of health disparities
      for the practice of urban medicine, including the role that concentration of
      disadvantage plays among patients and practice sites and the need for quality
      improvement to mitigate these disparities.

PMID- 15563648
TI  - Overcoming the hurdles to providing urban health care in the 21st century.
AB  - The delivery of health care services to urban populations in the United States is
      a system of rapidly increasing complexity. With the emergence of superspecialized
      physicians, a scientific approach to disease management has received great
      emphasis. Those providing health care at the population level may also apply this
      evidence-based approach. Analysis of the process of health care delivery in its
      entirety is complicated, confusing, and may be fraught with bias. In this
      article, a powerful instrument for providing a scientific approach to urban
      health care health policy development is introduced. This tool allows for
      analysis and assessment of hurdles to health care delivery to urban populations
      by dividing the process into elements of "administration," "provision," and
      "utilization" (APU). This APU triangle model, while intuitive, also allows a more
      definitive analysis by parts than would be possible to make of the whole. Using
      this model, the authors explore some of the hurdles faced by each element as well
      as some potential solutions. Although this model is presented in the context of
      urban hurdles to health care, it is equally applicable to rural environments or
      other service-delivery systems. In conclusion, this article discusses the
      emergence of the role of the public health department as the facilitator and
      manager between sectors of the community not traditionally connected in a
      collaborative health care model. Thus, the urban public health department
      coordinates efforts to surmount the hurdles and provides the venue for analysis,
      development, and employment of successful strategies.

PMID- 15563649
TI  - Montefiore Medical Center in The Bronx, New York: improving health in an urban
      community.
AB  - The author calls on academic medical centers that serve urban communities to go
      beyond the traditional mission of patient care, teaching, and research by
      accepting responsibility to build community-based care systems that are capable
      of improving the health of underserved populations within their reach. The
      experience of Montefiore Medical Center in the Bronx, New York, is presented to
      illustrate the nature, scope, and complexity of the undertaking that is required.
      Eight initiatives are described: expanding the primary care network, creating The
      Children's Hospital at Montefiore and the Child Health Network, responding to the
      needs of other high-risk populations, integrating the network with health
      information technology, using care-management systems to improve quality,
      reinforcing ethical allocation of resources, building teaching and research into
      the network, and preserving community vitality. The author believes that the
      current health care environment offers opportunities that may help to stimulate
      change in the direction of community-based systems. Managed care provides
      financial incentives to academic centers that are willing to accept risk and
      responsibly manage the care of a defined community, and advanced information
      technologies can support them in that endeavor. The author concludes that for
      academic medical centers with the proper systems in place, accepting
      responsibility for the community is not only the right thing to do, it is the
      strategic thing to do.

PMID- 15563650
TI  - The role of U.S. public hospitals in urban health.
AB  - Public hospitals in the United States play a key role in urban health. In many
      metropolitan communities, public hospitals maintain the health care safety net.
      Most urban public hospitals have evolved to not only provide care for the
      indigent but also to serve their communities in other ways, including serving as
      major providers for tertiary services such as trauma and those that support
      homeland security; serving as the foundation for primary care services;
      continuing to train a significant number of physician, nurses, and other medical
      personnel; and providing laboratories for clinical medical research. Federal
      budget cuts such as those in the Balanced Budget Act of 1997, recent state budget
      deficits, competition for Medicaid Managed Care, and the growth in the number of
      uninsured have led to a decline in revenues among urban public hospitals. To be
      better stewards of scarce resources, public hospitals have moved to reduce
      inpatient demand by adopting prevention strategies that are aimed at addressing
      the determinants of health, the complex interactions among social and economic
      factors, the physical environment, and individual behavior. These factors
      contribute to health status and offer opportunities to intervene and improve
      community health. Urban public hospitals, to be successful in the next stage of
      their evolution, need to learn to manage the "in-betweens"--partnering with
      governmental and nongovernmental entities to identify and work together on common
      health and safety issues. If public hospitals engage the community successfully,
      building trust and establishing new capability and capacity, urban public
      hospitals will survive, evolve, and continue their tradition of service.

PMID- 15563651
TI  - The Johns Hopkins Urban Health Institute: A collaborative response to urban
      health issues.
AB  - The authors provide background on the poor health and economic status of the
      residents of East Baltimore, Maryland--the neighborhood surrounding a significant
      part of Johns Hopkins University, including the School of Medicine, the School of
      Nursing, the Bloomberg School of Public Health, and the Johns Hopkins Hospital.
      The president of the Johns Hopkins University established a council on urban
      health, consisting of a broad array of individuals from across the university and
      the community to develop a recommended course of action to help deal with these
      conditions. Based on the recommendations of the council, the Johns Hopkins Urban
      Health Institute was established with the mission to marshall the resources of
      the university and external groups to improve the health and well-being of the
      residents of East Baltimore and to promote evidence-based interventions to solve
      urban health problems nationwide. After becoming fully operational in 2001, the
      institute established three major goals: (1) strengthen research and learning,
      (2) reduce disparities in health and health care for East Baltimore residents,
      and (3) promote economic growth in East Baltimore. The article describes the
      institute's major activities, including community-based participatory research
      projects, the Journal of Community-Based Participatory Research, and programs for
      research fellows to promote research and learning; HIV/AIDS counseling and
      testing centers and a primary care clinic for the uninsured to reduce health
      disparities; and a technology resource center providing training and job
      opportunities to promote economic growth. The authors conclude by outlining the
      next steps planned for the institute.

PMID- 15563652
TI  - Addressing the urban pipeline challenge for the physician workforce: the Sophie
      Davis model.
AB  - The convergence of numerous trends indicates that a physician shortage by 2020 is
      likely. There is a 25% growth in the overall population, but that of the college
      age sector is increasing by only 5%. The numbers of African Americans and Latinos
      in that sector will increase more than will members of other population groups;
      these two groups are most affected by the uneven quality of science education in
      urban high schools. Challenges to create a pipeline of a large, diverse, and
      qualified pool of medical school applicants are great, and are influenced by the
      actual and perceived cost of medical school tuition and the competition from
      other professions. Since 1973, the Sophie Davis School of Biomedical Education, a
      seven-year joint BS/MD program, has expanded access to medical school education
      for talented inner-city youths, including minorities and those with limited
      financial resources. Students receive a BS degree and their first two years of
      medical school education and, upon successful completion of the United States
      Medical Licensing Examination Step 1, transfer to one of five cooperating medical
      schools in New York State that confer the terminal MD degree. Sophie Davis
      integrates medical studies in the baccalaureate program, using actual performance
      in medical studies as a predictor of success. Of the more than 1,400 of its
      graduates, 25% are African American, 8% are Latino, 28% are Asian American, and
      39% are white. Over 25% of its current student body comes from federally defined
      low-income families, and almost three-quarters qualify for New York State
      financial aid. The Sophie Davis School of Biomedical Education is a model that
      offers a partial response to those factors that will challenge the achievement of
      an adequate supply of physicians for our urban communities. The author describes
      the model in detail and explains how it helps talented but unevenly educated
      students rise to the challenge of a medical education.

PMID- 15563653
TI  - Educating the next generation of pediatricians in urban health care: the Anne E.
      Dyson Community Pediatrics Training Initiative.
AB  - To improve the health of children who are exposed to urban health risks, there
      has been a national recognition of the need for better models of training
      pediatricians. In 2000, in response to this need, the Dyson Foundation launched a
      new residents-training model that focuses on community health and advocacy, The
      Anne E. Dyson Community Pediatrics Training Initiative (the Initiative). The
      Initiative is made up of 12 programs at ten sites, which are working in their
      communities to improve the health of the children. At its core are five
      objectives: to equip residents with tools and knowledge to provide community
      based health care, to make use of community resources so that residents learn to
      practice as medical home providers, to engage residents in the communities in
      which they work, to develop meaningful partnerships between departments of
      pediatrics and their communities, and to enhance pediatrics training through
      interdisciplinary collaborations among schools and departments. Curricular
      approaches at the participating sites differ slightly, but all have explicitly
      incorporated teaching community pediatrics into their standard rotations and
      continuity clinics. The authors showcase the programs of the Initiative and
      explore how the programs have sought buy-in from their parent institutions,
      faculty, residents, and communities.

PMID- 15563654
TI  - Educating social workers to meet the challenge of an aging urban population: a
      promising model.
AB  - As Americans live longer, they will require more health and social services to
      address the onset of acute and chronic conditions. The persistent changes in
      health care delivery and the increasingly diverse older adult population in urban
      settings, coupled with the high expectation for families to be responsible for
      home care needs, challenge social workers, who work alongside physicians, nurses,
      and other health care professionals, to provide services effectively. Because
      social workers are becoming more essential, social work education must increase
      the numbers of social workers with the knowledge and skills necessary for
      practice in the current U.S. health, mental health, and social service systems,
      particularly in caring for the aging populations in urban settings. A New York
      Academy of Medicine study identified the need for increased synergy between the
      two components of graduate social work education: the field experience and
      classroom instruction. One educational model, the Practicum Partnership Program,
      which is designed to better integrate field and classroom, is being tested at six
      sites. Early results from over 300 graduates are encouraging, with evidence that
      students' knowledge and skills regarding aging adults have increased, their
      satisfaction with the experience was very high, and those who were trained
      reflect the diversity of the population of older adults. The early success of
      this program suggests that innovative educational models that expose graduate
      social work students to diverse populations across the continuum of care are
      possible. Such models will be essential for the nation to be successful in
      producing a social work labor force qualified to meet the challenge of an aging
      urban population.

PMID- 15563655
TI  - Urban bioethics: adapting bioethics to the urban context.
AB  - Urban bioethics is an area of inquiry within the discipline of bioethics that
      focuses on ethical issues, problems, and conflicts relating to medicine, science,
      health care, and the environment that typically arise in urban settings. Urban
      bioethics challenges traditional bioethics (1) to examine value concerns in a
      multicultural context, including issues related to equity and disparity, and
      public health concerns that may highlight conflict between individual rights and
      the public good, and (2) to broaden its primary focus on individual self
      determination and respect for autonomy to include examination of the interests of
      family, community, and society. Three features associated with urban life
      density, diversity, and disparity-affect the health of urban populations and
      provide the substrate for identifying ethical concerns and value conflicts and
      creating interventions to affect population health outcomes. The field of urban
      bioethics can be helpful in creating ethical foundations and principles for
      public health practice, developing strategies to respect diversity in health
      policy in a pluralistic society, and fostering collaborative work among
      educators, social scientists, and others to eliminate bias among health
      professionals and health care institutions to enhance patients' satisfaction with
      their care and ultimately affect health outcomes. Educational programs at all
      levels and encompassing all health professions are needed as a first step to
      address the perplexing and important problem of eliminating health disparities.
      Urban bioethics is both contributing to the social science literature in this
      area and helping educators to craft interventions to affect professional
      attitudes and behaviors.

PMID- 15563656
TI  - The Corner.

PMID- 15563658
TI  - A story that illustrates humanism in medicine: garlic every day, and other
      wisdom.

PMID- 15563659
TI  - Indeterminate colitis.
AB  - Indeterminate colitis (IC) originally referred to those 10-15% of cases of
      inflammatory bowel disease (IBD) in which there was difficulty distinguishing
      between ulcerative colitis (UC) and Crohn's disease (CD) in the colectomy
      specimen. However, IC is increasingly used when a definitive diagnosis of UC or
      CD cannot be made at colonoscopy, in colonic biopsies or at colectomy. The
      diagnostic difficulties may explain the variably reported prevalence of IC.
      Clinically, most patients with IC evolve to a definite diagnosis of UC or CD on
      follow up. The role of ancillary tests in the distinction of UC from CD is
      reviewed. The low sensitivity of serological markers limits their usefulness.
      Other tests include upper endoscopy and magnetic resonance imaging. The
      definition of IC may not be a purely histological one derived from resected
      specimens, but rather a clinicopathological one. This review offers some personal
      observations and viewpoints, and proposes an approach to some of the relatively
      more esoteric combinations of findings.

PMID- 15563660
TI  - Aneuploidy and malignancy: an unsolved equation.
AB  - Aneuploidy is frequently noted in malignant tumours. There is much controversy
      about its cause and effect in relation to malignant tumours. Failure of the
      spindle checkpoint caused by mutation of the responsible genes may be one of the
      important factors for the development of aneuploidy. Telomere dysfunction may
      also be a possible source of failure of cytokinesis resulting in aneuploidy.
      Evidence such as tumour specific aneuploidy, presence of aneuploidy in various
      preneoplastic conditions, increased frequency of genetic instability in aneuploid
      cell lines compared with diploid cells, and mutation of mitotic checkpoint genes
      suggests that aneuploidy possibly plays an active role in carcinogenesis. In this
      brief review, the various aspects of aneuploidy with special emphasis on its
      mechanism of development and impact on progression of cancer are discussed.

PMID- 15563661
TI  - Virtual microscopy.

PMID- 15563662
TI  - An open pathology computer system.

PMID- 15563663
TI  - Fatal pulmonary embolism in hospitalised patients: a necropsy review.
AB  - AIMS: To carry out a retrospective review of all postmortem reports during the
      period 1991 to 2000 at King's College Hospital, London, as an extension of a
      previous analysis performed for the period 1965 to 1990. METHODS: The number of
      deaths resulting from necropsy confirmed fatal pulmonary embolism in hospitalised
      patients was determined, and a limited analysis of the clinical characteristics
      of those patients who died was performed. RESULTS: During the 10 year period, 16
      104 deaths occurred and 6833 (42.4%) necropsies were performed. The outcome
      measure, fatal pulmonary embolism, was recorded as cause of death in 265 cases
      (3.9% of all necropsies; 5.2% of adult cases). No deaths from pulmonary embolism
      occurred in patients under 18 years of age; 80.0% occurred in patients older than
      60 years. Of the fatal emboli, 214 of 265 (80.8%) occurred in patients who had
      not undergone recent surgery. Of these patients, 110 (51.4%) had suffered an
      acute medical illness in the six weeks before death, most often an acute
      infectious episode (26 cases). CONCLUSIONS: Thromboembolic events remain a
      relatively common cause of death in hospitalised patients and appear to occur
      more frequently in non-surgical than in surgical patients.

PMID- 15563664
TI  - Clonal B cell populations in a minority of patients with Hashimoto's thyroiditis.
AB  - BACKGROUND: Hashimoto's thyroiditis (HT) is a risk factor for thyroid lymphoma,
      and clonal B cell populations in HT support this link. The literature on B cell
      clonality in HT is controversial. AIMS: To identify clonal B cell populations in
      HT and to assess their usefulness in differentiating HT from mucosa associated
      lymphoid tissue (MALT) lymphoma and predicting future development of lymphoma.
      METHODS: DNA from formalin fixed, paraffin wax embedded blocks of thyroid
      specimens from 10 patients with HT and two thyroid MALT lymphomas was analysed
      for B cell clonality by seminested polymerase chain reaction (PCR) using
      FRIII/LJH and FRIII/VLJH primers to amplify the IgH gene VDJ region. In one case,
      PCR products were sequenced. Immunohistochemistry was performed by labelled
      streptavidin-biotin technique using antibodies to: CD45, CD45RO, CD3, CD20, and
      cytokeratin. RESULTS: The histopathological and clinical findings were
      characteristic of HT. Clonal bands were seen in three and a polyclonal smear
      pattern was seen in seven cases. The clonal bands in HT were associated with a
      background smear, and could not be reproduced from other blocks from the same
      case or from deeper sections of the same block. The clonal bands in thyroid
      lymphomas were not associated with a background smear and were reproducible. None
      of the patients with clonal B cells has developed malignant lymphoma during a
      follow up of 10-13 years. CONCLUSIONS: B cell clonal bands in HT have different
      features from those in lymphoma (non-pure and non-reproducible) and do not
      predict future development of lymphoma.

PMID- 15563665
TI  - Comparison of PCR and antigen detection methods for diagnosis of Entamoeba
      histolytica infection.
AB  - AIMS: To assess different laboratory methods for the identification of Entamoeba
      histolytica in clinical samples. METHODS: Antigen detection enzyme linked
      immunosorbent assay, polymerase chain reaction solution hybridisation enzyme
      linked immunoassay (PCR-SHELA), and a commercial Lightcycler PCR were compared
      using 101 stool and pus samples. RESULTS: Fifteen of the 101 samples were
      positive for E histolytica by one or more method. There were discrepancies
      between the results in five of these 15 samples when the assays were compared.
      CONCLUSIONS: All three methods performed adequately, so that the choice of assay
      will depend on each individual laboratory's budget and projected turnaround time.

PMID- 15563666
TI  - MUC4 is increased in high grade intraepithelial neoplasia in Barrett's oesophagus
      and is associated with a proapoptotic Bax to Bcl-2 ratio.
AB  - BACKGROUND: Patients with Barrett's oesophagus (BO) are at risk of oesophageal
      adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic
      progression, it may serve as a marker of intraepithelial neoplasia. AIMS: To
      determine the expression pattern of mucins in neoplastic BO epithelium (high
      grade dysplasia) and correlate it with the expression of apoptosis markers Bax
      and Bcl-2. METHODS: Thirty seven patients with BO were studied: 16 without
      intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN),
      and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous
      epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or
      adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined
      by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by
      immunoblotting. RESULTS: Mucin expression varied between neoplastic progression
      stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4,
      and were at least four times higher in BO and HGN (p<0.001), but less so in
      adenocarcinoma. MUC4 expression was significantly lower in BO than in normal
      squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly
      higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared
      with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA
      data. CONCLUSIONS: Mucin expression varies during the development of oesophageal
      adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In
      contrast to animal studies, upregulation of MUC4 in HGN is associated with
      increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis
      regulation in BO.

PMID- 15563667
TI  - Identification of helicobacter species in human liver samples from patients with
      primary hepatocellular carcinoma.
AB  - AIMS: Several studies have shown the presence of helicobacter species in the
      human biliary tract and in the intestinal tract of animals. Experimental
      infection by Helicobacter hepaticus in mice causes chronic hepatitis and
      hepatocellular carcinoma (HCC). This study investigated whether helicobacter
      species could be detected in the liver of patients with HCC. METHODS: Liver
      samples from 20 patients with primary liver carcinoma diagnosed by histopathology
      and 16 controls without primary liver carcinoma were studied. Histology with
      standard and immunohistochemical stains, culture, and polymerase chain reaction
      (PCR) amplification using helicobacter genus specific 16S rRNA primers were used
      to detect the presence of bacteria. Amplified products were identified by
      Southern hybridisation and sequencing. A search for other genes specific for
      Helicobacter pylori was also performed. RESULTS: Helicobacter species 16S rDNA
      was found in eight of 20 samples of primary liver carcinoma, whereas none of the
      controls harboured this rDNA. Six helicobacter specific PCR amplicons were
      sequenced and were found to have 98.5-99.0% similarity to the 16S rDNA of H
      pylori. Of the eight positive samples, seven were positive in PCR using 26 kDa
      protein primers and six showed morphological and immunohistochemical evidence of
      H pylori. The cagA and glmM genes were detected in only two samples. The vacA and
      rps4 genes were not detected. CONCLUSIONS: Helicobacter can be present in the
      liver of patients with primary liver carcinoma and is probably linked to the
      carcinogenic process in the liver.

PMID- 15563668
TI  - Design of a real time quantitative PCR assay to assess global mRNA amplification
      of small size specimens for microarray hybridisation.
AB  - BACKGROUND: Low RNA yields from clinical samples are a limiting step for
      microarray technology. AIMS: To design an accurate real time quantitative
      polymerase chain reaction (PCR) assay to assess the crucial step of global mRNA
      amplification performed before microarray hybridisation, using less than 1 microg
      total RNA. METHODS: Three RNA extraction procedures were compared for small size
      samples. Total RNA was amplified from universal RNA or the BC-H1 breast cancer
      micrometastatic cell line using three different protocols. Real time quantitative
      PCR technology was used for accurate measurement of urokinase plasminogen
      activator receptor and cytokeratin 8 RNA amplification rates and ratios, using
      primer sets binding at various distances from the 3' end of transcripts. A 50 mer
      oligomeric array targeting 87 genes potentially involved in breast cancer
      metastatic progression was built and hybridised with amplified RNA. RESULTS:
      Eighteen nanograms of total RNA could be purified from 1000 BC-H1 micrometastatic
      cells. Amplification rates of 25,000 to 100,000 were achieved with as little as
      10 ng of starting material. However, results were highly variable, depending on
      the amount of starting material, gene characteristics, sample quality, and
      protocols used. Oligomeric array hybridisation with 20 microg reference RNA
      resulted in specific and reproducible signals for 83% of the genes, whereas mRNA
      amplification from less than 400 ng of starting material resulted in selective
      detection of signals from highly expressed genes. CONCLUSIONS: Improvements in
      the design of global mRNA amplification procedures and oligomeric arrays are
      needed to extract informative gene expression data from clinical samples
      containing limited cell numbers.

PMID- 15563669
TI  - A digital atlas of breast histopathology: an application of web based virtual
      microscopy.
AB  - AIMS: To develop an educationally useful atlas of breast histopathology, using
      advanced web based virtual microscopy technology. METHODS: By using a robotic
      microscope and software adopted and modified from the aerial and satellite
      imaging industry, a virtual microscopy system was developed that allows fully
      automated slide scanning and image distribution via the internet. More than 150
      slides were scanned at high resolution with an oil immersion x 40 objective
      (numerical aperture, 1.3) and archived on an image server residing in a high
      speed university network. RESULTS: A publicly available website was constructed,
      http://www.webmicroscope.net/breastatlas, which features a comprehensive virtual
      slide atlas of breast histopathology according to the World Health Organisation
      2003 classification. Users can view any part of an entire specimen at any
      magnification within a standard web browser. The virtual slides are supplemented
      with concise textual descriptions, but can also be viewed without diagnostic
      information for self assessment of histopathology skills. CONCLUSIONS: Using the
      technology described here, it is feasible to develop clinically and educationally
      useful virtual microscopy applications. Web based virtual microscopy will
      probably become widely used at all levels in pathology teaching.

PMID- 15563670
TI  - The perforin mediated apoptotic pathway in lung injury and fibrosis.
AB  - AIMS: The perforin mediated pathway is the major pathway of cytotoxicity induced
      by activated T cells and natural killer cells, and may be involved in the
      development of pulmonary fibrosis. METHODS: Perforin and granzyme B expression
      were examined in idiopathic pulmonary fibrosis by means of immunohistochemistry,
      and perforin knockout mice were used to examine whether or not perforin mediated
      cytotoxicity participates in the pathophysiology of bleomycin induced
      pneumopathy. RESULTS: Perforin and granzyme B expression were upregulated in
      infiltrating lymphocytes in lung tissue from patients with idiopathic pulmonary
      fibrosis compared with normal lung parenchyma. Perforin and granzyme B expression
      were upregulated predominantly in infiltrating mononuclear cells after bleomycin
      instillation in wild-type mice. Although the development of bleomycin induced
      pneumopathy was not completely prevented, the pathological grade of inflammation
      and fibrosis, and the number of apoptotic cells in lung tissue, were
      significantly decreased in perforin knockout mice compared with wild-type mice.
      CONCLUSIONS: These results suggest that perforin mediated apoptosis may be
      associated with the pathophysiology of lung injury and fibrosis.

PMID- 15563671
TI  - The role of serum insulin-like growth factor I (IGF-I) in neonatal outcome.
AB  - AIMS: To determine the role of serum insulin-like growth factor I (IGF-I) in
      predicting the occurrence of septal hypertrophic cardiomyopathy in infants of
      mothers with diabetes. METHODS/MATERIALS: In this prospective study, 100 pregnant
      women (50 with diabetes and 50 controls), matched for age and race, were studied.
      One intrapartum blood sample was taken at 28 weeks of gestation from both groups
      of mothers and another sample at delivery. All samples were analysed for maternal
      IGF-I by an enzyme linked immunosorbent assay method. A chest radiograph and an
      electrocardiogram were performed on the babies of the mothers with diabetes
      within the first 24 hours of life. An echocardiogram was performed in the first 3
      days of life to look for septal hypertrophy and to measure the myocardial
      thickness. RESULTS: In the six cases of neonatal septal hypertrophic
      cardiomyopathy, all the mothers had greatly raised IGF-I concentrations of more
      than 400 ng/ml at the time of delivery compared with a mean (SD) of 302 (25)
      ng/ml in control mothers. CONCLUSIONS: In the present study a crude analysis
      revealed that increased IGF-I concentrations correlate with neonatal septal
      hypertrophic cardiomyopathy.

PMID- 15563672
TI  - Impact of positive legionella urinary antigen test on patient management and
      improvement of antibiotic use.
AB  - AIM: To assess the incidence of legionella infection over a 27 month period at a
      large university hospital. MATERIAL AND METHODS: The present retrospective cohort
      study enrolled patients with legionellosis, defined as those presenting a
      positive urinary antigen for legionella together with a medical history, clinical
      findings, and radiological findings consistent with pneumonia. These patients
      were evaluated to determine the relation between their test results and changes
      in treatment modalities. A control group of patients with pneumonia but a
      negative urinary antigen test for legionella were also analysed. RESULTS: Twenty
      seven of 792 assessed patients tested positive for legionella. In 22 of these
      patients, legionella active antibiotics were administered empirically. In seven
      patients, the test results prompted a legionella specific treatment, whereas in
      12 cases, non-specific antibiotics were stopped within 24 hours. Overall,
      treatment was altered in more than half of the patients as a result of the test
      results. CONCLUSIONS: The urinary antigen may have a direct impact on clinical
      management of pulmonary legionellosis. However, patient comorbidities and
      individual clinical judgment are still important for determining the best
      treatment to be given in each individual case.

PMID- 15563673
TI  - Role of p53, apoptosis, and cell proliferation in early stage Epstein-Barr virus
      positive and negative gastric carcinomas.
AB  - AIMS: Mechanisms of Epstein-Barr virus (EBV) associated gastric tumour
      development are incompletely understood. The interrelations between EBV
      infection, apoptosis, cell proliferation, and the expression of the tumour
      suppressor gene p53 was investigated in 133 early stage gastric carcinomas.
      METHODS: Tumour tissue was compared with paired non-tumour tissue. EBV encoded
      small RNAs (EBERs) determined EBV status. The apoptotic index (AI) was determined
      by morphology and verified biochemically. p53 and Ki-67 expression (cell
      proliferation) was assessed using immunohistochemistry. RESULTS: EBV was detected
      in 14.3% of the cases. Cell proliferation did not differ significantly between
      EBV positive and negative cancers. However, within both these groups, the p53
      positive and negative subsets differed significantly (EBV positive group: 76.8%
      and 55.3% were p53 positive or negative cancers, respectively; p<0.05; EBV
      negative group: 65.2% and 51.7% were p53 positive or negative, respectively;
      p<0.005). The numbers of p53 expressing EBV positive and negative cases were
      significantly different (57.9% and 82.5%, respectively; p<0.05). Compared with
      cell proliferation, apoptosis was significantly lower in EBV positive versus
      negative cancers (AI of 4.36 and 6.50, respectively; p<0.01). The p53 positive
      and negative subsets also differed significantly in AI (EBV positive group: AI of
      5.13 and 3.30 for p53 positive and negative cancers, respectively; p<0.05: EBV
      negative group: AI of 6.84 and 4.90 for p53 positive and negative cancers,
      respectively; p<0.05). CONCLUSIONS: These factors probably combine to promote
      development and progression of early stage gastric carcinomas and, at the same
      time, ensure the survival of EBV itself.

PMID- 15563674
TI  - nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma.
AB  - BACKGROUND: The discovery that genetic alterations in oncogenes and tumour
      suppressor genes accompany tumour formation in many human tumours has encouraged
      the search for genes that promote or suppress tumour spread and metastasis; nm23
      is a promising candidate for a metastasis suppressing gene. AIMS: To evaluate
      whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23
      H1 gene is associated with colon cancer progression. MATERIALS/METHODS: Paraffin
      wax embedded tissue sections were analysed immunohistochemically. DNA isolated
      from normal and tumour tissue was used for LOH analysis using a variable
      nucleotide tandem repeat (VNTR) marker located in the untranslated 5' region of
      the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for "real
      time" RT-PCR. RESULTS: Of 102 adenocarcinomas examined, 58.8% stained weakly for
      nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and
      tumour histological grade. In VNTR analysis, 70.2% of patients were informative
      and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between
      nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of
      nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue.
      No significant correlation was found between nm23-H1 mRNA expression and
      histological grade or Dukes's stage of tumours. CONCLUSIONS: These findings
      suggest that nm23-H1 protein expression in early stages may have a role in
      suppressing metastasis in sporadic colon cancer, whereas at a later stage both
      reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in
      colon cancer progression and metastasis.

PMID- 15563675
TI  - Primary intratesticular leiomyosarcoma in a mixed race man: a case report.
AB  - Primary leiomyosarcoma of the testis is an extremely rare condition with only a
      few reported cases in the literature. None has been reported in men of Afro
      Caribbean descent. This report describes the first case of a primary
      leiomyosarcoma in a mixed race man. Several different immunostains were used to
      confirm the morphological suggestion of a primary intratesticular smooth muscle
      tumour. Scrotal ultrasound and abdominal computed tomography imaging were used to
      exclude paratesticular and retroperitoneal pathology. Where reported, primary
      intratesticular leiomyosarcoma is described as an indolent tumour with the
      potential for distant metastases. Its occurrence in younger men is usually
      associated with anabolic steroid abuse. Although the number of reported cases is
      very few, radical orchidectomy followed by surveillance appears to be the
      treatment of choice.

PMID- 15563676
TI  - Surviving acute myocardial infarction: survivin expression in viable
      cardiomyocytes after infarction.
AB  - BACKGROUND: Apoptosis is a key feature in postinfarction remodelling leading to
      progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute
      to the delicate balance between death and survival. The survivin pathway has
      emerged as essential in the control of apoptosis, although its role in heart
      disease is unknown. AIM: To evaluate survivin expression after acute myocardial
      infarction (AMI). METHODS: Survivin expression was assessed immunohistochemically
      in the peri-infarct and remote viable myocardium in 17 consecutive patients who
      died 1-30 weeks after AMI and in four control hearts. RESULTS: Survivin was
      expressed by myocytes in the peri-infarct area in eight patients and in the
      remote region in 13 patients. The rate of survivin expression after AMI was
      significantly higher in the remote versus peri-infarct regions and compared with
      control hearts. Its expression was inversely associated with the presence of
      dilated cardiopathy and of apoptosis, independently from the gross pathology
      infarct size. CONCLUSIONS: Survivin myocardial expression after AMI may be
      associated with the survival of at risk myocardium and may be indicative of more
      favourable remodelling after AMI. These findings identify a potential new target
      for the treatment of postinfarction remodelling.

PMID- 15563677
TI  - Transition of Sezary syndrome into mycosis fungoides after complete clinical and
      molecular remission under extracorporeal photophoresis.
AB  - Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common clinical
      variants of cutaneous T cell lymphoma. Although thought to be closely related to
      mature T helper cells, the relation between the neoplastic cells in MF and SS is
      still not fully clarified. This report describes a patient with complete
      remission of SS under treatment with extracorporeal photophoresis (ECP), who
      subsequently developed typical plaques of MF and large cell lymphoma (LCL).
      Serial polymerase chain reaction analyses confirmed identical T cell receptor
      beta and gamma gene rearrangements in SS, MF, and LCL, and complete disappearance
      of the circulating malignant T cell clone from the peripheral blood after ECP.
      These findings indicate that the neoplastic cells in SS, MF, and LCL are derived
      from a common precursor T cell, despite the change in clinical phenotype.

PMID- 15563678
TI  - Benign mixed tumour of the skin with extensive ossification and marrow formation:
      a case report.
AB  - Benign mixed tumour of the skin (chondroid syringoma) is an uncommon skin adnexal
      tumour, usually presenting as a slow growing solitary painless nodule. The
      morphological appearances are similar to those of a pleomorphic adenoma of the
      salivary gland. Hair matrix and sebaceous differentiation can be seen in some
      lesions. Focal ossification is a rare finding. This report presents a case of a
      similar tumour arising in the cheek of a 43 year old white man, showing extensive
      ossification. Clinical, radiological, and pathological correlation and diagnosis
      proved to be difficult preoperatively. Only two cases of a benign mixed tumour
      with pronounced ossification have been reported so far, both in Japanese
      patients. This is the first reported case seen in a white man. Awareness of these
      lesions will avoid potential diagnostic pitfalls.

PMID- 15563679
TI  - Virilisation in a case of transitional cell carcinoma of the ovary.
AB  - A 52 year old woman presented with a five month history of emotional changes,
      voice changes, and of abdominal discomfort. Clinical, biochemical, and
      radiological examinations showed evidence of virilisation, raised testosterone,
      and a complex ovarian mass. Microscopy of the resection specimen showed the
      tumour to be a transitional cell carcinoma of the ovary with luteinisation and
      hyperplasia of the intervening stromal cells. This is a unique case of
      virilisation caused by transitional cell carcinoma of the ovary. Theories as to
      the origin of testosterone production in non-functioning ovarian tumours are
      discussed.

PMID- 15563680
TI  - The case of the floating gel.
AB  - In patients with chronic renal failure, blood samples for laboratory analysis are
      often taken via dialysis catheters. This report describes a case of gross
      spurious hypernatraemia in a blood sample collected from a patient undergoing
      haemodialysis. After centrifugation of the blood sample in question, the
      separator gel formed the topmost layer, with the serum in the middle and the clot
      at the bottom. Subsequent analysis of the serum showed severe hypernatraemia
      (serum sodium, 744 mmol/litre). It was established that the blood sample had been
      taken from the patient's dialysis catheter into which 3 ml of Citra-Lock (46.7%
      trisodium citrate) had been instilled previously as a "catheter locking"
      solution. The hypernatraemia seen in this case was recognised immediately as an
      artefact, but it was found that even minimal contamination of blood samples with
      Citra-Lock may significantly affect sodium concentrations. This contamination may
      be missed, with potentially adverse consequences for patient management.

PMID- 15563681
TI  - Sialometaplasia arising in the ectopic salivary gland ductal inclusions of
      multiple intraparotid lymph nodes.
AB  - Sialometaplasia, squamous metaplasia of salivary gland lobules, is a benign
      condition occasionally presenting with lesions clinically simulating malignancy.
      "Necrotising sialometaplasia", recognised by lobular infarction, necrosis, and
      simultaneous squamous metaplasia of ducts and acini is a well known condition.
      There are only a few reports of the "proliferative type of sialometaplasia",
      which is recognised by a more mature morphology of larger and more irregular
      metaplastic nests, lacking necrosis. This report describes a unique case of
      "proliferative sialometaplasia of multiple intraparotid lymph nodes" occurring in
      a 55 year old woman, presenting with multiple parotid lumps. This interesting
      case points to the importance of intraparotid lymph nodes as sites for multiple
      lesions of the parotid region.

PMID- 15563682
TI  - Unusual cardiac tumour with perivascular myoid differentiation: a case report.
AB  - A previously healthy 70 year old woman was admitted for fatigue and dyspnoea on
      exertion and cough. A two dimensional echocardiography revealed a mass in the
      right atrium, which obstructed filling and infiltrated the cardiac chamber wall.
      Postsurgical histological examination revealed an unusual tumour with prevalent
      myoid glomangiopericytoma-type and haemangiopericytoma-like patterns. Mitosis and
      necrosis were absent. A computed tomography scan excluded the presence of
      metastasis to distant organs or, conversely, metastatic involvement of the heart.
      Therefore, a diagnosis of tumour with perivascular myoid differentiation was
      made. This new entity, recently described in soft tissues, can easily recur. Its
      recognition helps to differentiate from metastasis and other primitive cardiac
      tumours sharing some morphological features but a different clinical behaviour,
      with consequent improvement to the management of patient care.

PMID- 15563683
TI  - Ciliated cell variant of endometrioid adenocarcinoma: a rare tumour.

PMID- 15563684
TI  - Vocal cord biopsy leading to the diagnosis of hyperlipidaemia.

PMID- 15563685
TI  - Lack of lymphangiogenesis during breast carcinogenesis.

PMID- 15563686
TI  - Pathologists' slide storage: ice age technology comes to the rescue.

PMID- 15563687
TI  - IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or
      eotaxin by effects on airway smooth muscle.
AB  - IL-13 is a mediator of allergen-induced airway hyperresponsiveness (AHR). The aim
      of this study was to evaluate whether eotaxin and IL-5 were implicated in the
      effects of IL-13 on allergen-induced AHR or whether IL-13 may exert its effects
      through direct actions on airway smooth muscle (ASM). To study this question
      airway inflammation and AHR were induced in mice by sensitization and subsequent
      challenge on three successive days with ovalbumin. A monoclonal anti-IL-13
      antibody administered before each challenge significantly reduced AHR without
      affecting airway eosinophilia. No changes of mRNA in BAL and lung tissues or
      protein levels in BAL of IL-5 or eotaxin were found following anti-IL-13
      treatment. Combined injection of monoclonal anti-IL-5 and antieotaxin antibodies
      before each antigen challenge blocked airway eosinophilia but failed to reduce
      AHR. IL-13 induced calcium transients in cultured murine ASM cells and augmented
      the calcium and contractile responses of these cells to leukotriene D4. These
      results suggest that IL-13 plays an important role in allergen-induced AHR and is
      important in the early phases of the inflammatory process. Its effects on AHR are
      mediated independently of IL-5 and eotaxin and may involve a direct effect on ASM
      to augment its responsiveness.

PMID- 15563688
TI  - Protease-activated receptor-1 in human lung fibroblasts mediates a negative
      feedback downregulation via prostaglandin E2.
AB  - Among the four protease-activated receptors (PARs), PAR-1 plays an important role
      in normal lung functioning and in the development of lung diseases, including
      fibrosis. We compared the expression and functional activity of PARs in normal
      and fibrotic human lung fibroblasts. Both normal and fibrotic cells express PAR
      1, -2, and -3, with PAR-2 showing the lowest level. There was no significant
      difference between normal and fibrotic fibroblasts in expression levels of PAR-1
      and PAR-3, whereas a fourfold higher expression level of PAR-2 was observed in
      fibrotic cells compared with normal cells. Ca(2+) imaging studies revealed
      apparently only PAR-1-induced Ca(2+) signaling in lung fibroblasts. PAR-1
      agonists, thrombin and synthetic activating peptide, induced concentration
      dependent Ca(2+) mobilization with EC(50) values of 5 nM and 1 microM,
      respectively. The neutrophil protease cathepsin G produced a transient Ca(2+)
      response followed by disabling PAR-1, whereas elastase did not affect Ca(2+)
      level. PAR-1 activation by thrombin or receptor-activating peptide downregulated
      expression of all three PARs in lung fibroblasts, with maximal effect at 3-6 h,
      whereas expression returned toward basal level after 24 h. Furthermore, PAR-1
      agonists dose dependently increased PGE(2) secretion from lung fibroblasts and
      induction of cyclooxygenase-2 expression. We then found that PGE(2) downregulated
      expression of all three PARs. The effect of PGE(2) was continuously growing with
      time. Furthermore, PGE(2) exerts its effect through the EP2 receptor that was
      confirmed using the selective EP2 agonist butaprost. This novel autocrine
      feedback mechanism of PGE(2) in lung fibroblasts seems to be an important
      regulator in lung physiology and pathology.

PMID- 15563689
TI  - LPS activation of Toll-like receptor 4 signals CD11b/CD18 expression in
      neutrophils.
AB  - We identify herein a novel signaling function of the Toll-like receptor-4 (TLR4),
      the lipopolysaccharide (LPS) receptor mediating the innate immune response, in
      inducing the expression of CD11b/CD18 integrin in polymorphonuclear leukocytes
      (PMNs). Studies were made in PMNs isolated from TLR4-deficient (TLR4(-/-)) and
      C57BL/6 [wild-type (WT)] mice. We observed increased CD11b expression in WT PMNs
      within 3 h after LPS challenge, whereas CD11b was not expressed in TLR4(-/-) PMNs
      above basal levels. TLR4-activated CD11b expression was cycloheximide sensitive
      and involved the activation of transcription factors, NF-kappaB and c-Jun/PU.1.
      TLR4(-/-) PMNs challenged with LPS were functionally defective as the result of
      the impaired CD11b expression in that they failed to adhere and did not migrate
      across endothelial cells in response to N-formylmethionyl-leucyl-phenylalanine.
      TLR4 also promoted increased binding of LPS to PMNs on the basis of expression of
      CD11b. Thus TLR4 signaling activates synthesis and upregulation of CD11b and is
      essential for PMN adhesion and transmigration. Our data suggest an important role
      of TLR4-activated CD11b expression in the mechanism of the PMN host-defense
      response to LPS.

PMID- 15563690
TI  - Mitochondrial DNA damage triggers mitochondrial dysfunction and apoptosis in
      oxidant-challenged lung endothelial cells.
AB  - Oxidant-induced death and dysfunction of pulmonary vascular cells play important
      roles in the evolution of acute lung injury. In pulmonary artery endothelial
      cells (PAECs), oxidant-mediated damage to mitochondrial DNA (mtDNA) seems to be
      critical in initiating cytotoxicity inasmuch as overexpression of the
      mitochondrially targeted human DNA repair enzyme, human Ogg1 (hOgg1), prevents
      both mtDNA damage and cell death (Dobson AW, Grishko V, LeDoux SP, Kelley MR,
      Wilson GL, and Gillespie MN. Am J Physiol Lung Cell Mol Physiol 283: L205-L210,
      2002). The mechanism by which mtDNA damage leads to PAEC death is unknown, and
      the present study tested the specific hypothesis that enhanced mtDNA repair
      suppresses PAEC mitochondrial dysfunction and apoptosis evoked by xanthine
      oxidase (XO). PAECs transfected either with an adenoviral vector encoding hOgg1
      linked to a mitochondrial targeting sequence or with empty vector were challenged
      with ascending doses of XO plus hypoxanthine. Quantitative Southern blot analyses
      revealed that, as expected, hOgg1 overexpression suppressed XO-induced mtDNA
      damage. Mitochondrial overexpression of hOgg1 also suppressed the XO-mediated
      loss of mitochondrial membrane potential. Importantly, hOgg1 overexpression
      attenuated XO-induced apoptosis as detected by suppression of caspase-3
      activation, by reduced DNA fragmentation, and by a blunted appearance of
      condensed, fragmented nuclei. These observations suggest that mtDNA damage serves
      as a trigger for mitochondrial dysfunction and apoptosis in XO-treated PAECs.

PMID- 15563691
TI  - Epithelial expression of profibrotic mediators in a model of allergen-induced
      airway remodeling.
AB  - Airway remodeling, including subepithelial fibrosis, is a characteristic feature
      of asthma and likely contributes to the pathogenesis of airway
      hyperresponsiveness. We examined expression of genes related to airway wall
      fibrosis in a model of chronic allergen-induced airway dysfunction using laser
      capture microdissection and quantitative real-time PCR. BALB/c mice were
      sensitized and subjected to chronic ovalbumin exposure over a 12-wk period, after
      which they were rested and then harvested 2 and 8 wk after the last exposure.
      Chronic allergen-exposed mice had significantly increased indices of airway
      remodeling and airway hyperreactivity at all time points, although no difference
      in expression of fibrosis-related genes was found when mRNA extracted from whole
      lung was examined. In contrast, fibrosis-related gene expression was
      significantly upregulated in mRNA obtained from microdissected bronchial wall at
      2 wk after chronic allergen exposure. In addition, when bronchial wall epithelium
      and smooth muscle were separately microdissected, gene expression of transforming
      growth factor-beta1 and plasminogen activating inhibitor-1 were significantly
      upregulated only in the airway epithelium. These data suggest that transforming
      growth factor-beta1 and other profibrotic mediators produced by airway wall, and
      specifically, airway epithelium, play an important role in the pathophysiology of
      airway remodeling.

PMID- 15563692
TI  - Monocytes recruited to the lungs of mice during immune inflammation ingest
      apoptotic cells poorly.
AB  - Apoptotic cells must be cleared to resolve inflammation, but few resident
      alveolar macrophages (AMo) from normal lungs ingest apoptotic cells. We examined
      how Mo ingestion of apoptotic cells is altered during immune inflammation induced
      by intratracheal challenge of primed C57BL/6 mice using sheep red blood cells.
      Resident AMo were labeled in situ before challenge using intravenous PKH26 to
      distinguish them from recruited monocytes. Using flow cytometry, we identified
      phagocytosis of fluorescently-labeled apoptotic thymocytes by alveolar
      mononuclear phagocytes in vitro and in vivo, and measured surface molecule
      expression. Intratracheal challenge induced rapid recruitment of monocytes,
      peaking at Day 3 and decreasing thereafter, whereas numbers of resident AMo did
      not change significantly. At all times, the percentage of phagocytes ingesting
      apoptotic thymocytes in vitro was greater among resident AMo (28-45%) than among
      recruited monocytes (9-19%), but was low in both cell types relative to ingestion
      of immunoglobulin-opsonized targets. There was also a nonsignificant trend toward
      lower ingestion by monocytes in vivo. MerTK, a receptor tyrosine kinase crucial
      for apoptotic cell phagocytosis, was expressed by resident AMo, but not by
      recruited monocytes. Relative to resident AMo, monocytes recruited to the
      alveolus ingest apoptotic cells meagerly, possibly due to absence of MerTK
      expression.

PMID- 15563693
TI  - Oxygen: the good, the bad, and the necessary...

PMID- 15563694
TI  - Non-invasive ventilation in acute exacerbations of COPD: what happens after
      hospital discharge?

PMID- 15563695
TI  - Detecting early lung disease in cystic fibrosis: are current techniques
      sufficient?

PMID- 15563696
TI  - Getting grant applications funded: lessons from the past and advice for the
      future.

PMID- 15563698
TI  - Supplementary oxygen in healthy subjects and those with COPD increases oxidative
      stress and airway inflammation.
AB  - BACKGROUND: Hyperoxia increases oxidative stress through the generation of
      reactive oxygen species and may therefore enhance inflammation in the lungs. The
      aim of this study was to investigate whether short term supplementary oxygen
      (28%) increases oxidative stress and inflammation in the airways by measuring 8
      isoprostane and interleukin 6 (IL-6) concentrations in exhaled breath condensate.
      METHODS: Twenty three healthy subjects (12 men, mean (SD) age 48 (7) years) and
      23 patients with chronic obstructive pulmonary disease (COPD; 15 men, mean (SD)
      age 56 (5) years) were studied. 8-isoprostane and IL-6 concentrations were
      measured by immunoassay. RESULTS: Increased concentrations of 8-isoprostane and
      IL-6 were found in all subjects after breathing 28% oxygen for 1 hour. In healthy
      subjects the concentrations of 8-isoprostane and IL-6 were 10.9 (2.9) pg/ml and
      4.9 (0.8) pg/ml, respectively, compared with baseline concentrations of 6.1 (1.3)
      pg/ml and 2.9 (0.6) pg/ml, and in patients with COPD the concentrations were 27.9
      (3.1) pg/ml and 8.3 (1.2) pg/ml), respectively, compared with baseline
      concentrations of 18.9 (3.6) pg/ml and 6.3 (0.6) pg/ml. By contrast, breathing
      air through the same face mask for 1 hour had no significant effects on 8
      isoprostane or IL-6 concentrations in normal subjects or those with COPD.
      CONCLUSIONS: These findings suggest that short term supplementary oxygen may
      enhance oxidative stress and inflammation in the airways. Whether this happens
      with long term oxygen therapy needs to be determined.

PMID- 15563699
TI  - Readmission rates and life threatening events in COPD survivors treated with non
      invasive ventilation for acute hypercapnic respiratory failure.
AB  - BACKGROUND: Non-invasive ventilation (NIV) has been shown to reduce intubation
      and in-hospital mortality in patients with chronic obstructive pulmonary disease
      (COPD) and acute hypercapnic respiratory failure (AHRF). However, little
      information exists on the outcomes following discharge. A study was undertaken to
      examine the rates of readmission, recurrent AHRF, and death following discharge
      and the risk factors associated with them. METHODS: A cohort of COPD patients
      with AHRF who survived after treatment with NIV in a respiratory high dependency
      unit was prospectively followed from July 2001 to October 2002. The times to
      readmission, first recurrent AHRF, and death were recorded and analysed against
      potential risk factors collected during the index admission. RESULTS: One hundred
      and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after
      NIV during the study period. One year after discharge 79.9% had been readmitted,
      63.3% had another life threatening event, and 49.1% had died. Survivors spent a
      median of 12% of the subsequent year in hospital. The number of days in hospital
      in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early
      readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a
      lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the
      MRC dyspnoea score (p<0.001) predicted early death. CONCLUSIONS: COPD patients
      with AHRF who survive following treatment with NIV have a high risk of
      readmission and life threatening events. Further studies are urgently needed to
      devise strategies to reduce readmission and life threatening events in this group
      of patients.

PMID- 15563700
TI  - Continuous and intermittent exercise responses in individuals with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: While the acute physiological responses to continuous exercise have
      been well documented in individuals with chronic obstructive pulmonary disease
      (COPD), no previous study has examined the response to intermittent exercise in
      these patients. METHODS: We examined the physiological responses of 10
      individuals with moderate COPD (forced expiratory volume in 1 second 52 (15)%
      predicted) who performed both an intermittent (1 min exercise and rest intervals)
      and a continuous cycle ergometer test on separate days. Both intermittent and
      continuous exercise tests were performed at the same power output, calculated as
      70% of the peak power attained during an incremental exercise test. RESULTS:
      Intermittent exercise was associated with significantly lower values for oxygen
      uptake, carbon dioxide output, expired ventilation, heart rate, plasma lactate
      concentration, and ratings of breathlessness than continuous exercise. Subjects
      were able to complete a significantly greater total amount of work during
      intermittent exercise (71 (32) kJ) than during continuous exercise (31 (24) kJ).
      The degree of dynamic lung hyperinflation (change in end expiratory lung volume)
      was significantly lower during intermittent exercise (0.23 (0.07) l) than in
      continuous exercise (0.52 (0.13) l). CONCLUSIONS: The greater amount of work
      performed and lower measured physiological responses achieved with intermittent
      exercise may allow for greater peripheral training adaptations in individuals
      with more limited lung function. The results suggest that intermittent exercise
      may be superior to continuous exercise as a mode of training for patients with
      COPD.

PMID- 15563701
TI  - Expression of ErbB receptors and mucins in the airways of long term current
      smokers.
AB  - BACKGROUND: Airway epithelial goblet cell hyperplasia is known to occur in
      chronic smokers. Although the epidermal growth factor receptor has been
      implicated in this process, neither ErbB receptor expression nor the
      mucosecretory phenotype of the epithelium have been characterised in current
      smokers. METHODS: Bronchial biopsies obtained from non-smokers (n = 10) and
      current smokers, with or without chronic obstructive pulmonary disease (n = 51),
      were examined immunohistochemically to measure the expression of epidermal growth
      factor receptor, ErbB2, ErbB3, ErbB4 and mucin subtypes (MUC2, MUC5AC and MUC5B)
      in the bronchial epithelium. The results were correlated with neutrophil counts
      measured in the airway wall and induced sputum. RESULTS: Epidermal growth factor
      receptor, ErbB3 and MUC5AC expression, in addition to PAS staining, were
      significantly increased in all smokers compared with non-smokers, irrespective of
      the presence of chronic obstructive pulmonary disease. MUC5AC expression was
      significantly associated with both PAS staining and ErbB3 expression; no
      correlation was observed between either mucin or ErbB receptor expression and
      neutrophil counts. CONCLUSIONS: The results suggest that long term current
      smoking induces enhanced epidermal growth factor receptor, ErbB3, and MUC5AC
      expression in vivo; these increases are not associated with the presence of
      neutrophilic inflammation. ErbB receptors may contribute to epithelial responses
      to cigarette smoke.

PMID- 15563702
TI  - Initial starting dose of inhaled corticosteroids in adults with asthma: a
      systematic review.
AB  - BACKGROUND: Asthma guidelines vary in their recommendations for the initial dose
      of inhaled corticosteroid (ICS) in asthma. A systematic review of the literature
      was conducted to establish the optimal starting dose of ICS for asthma in adults.
      METHODS: Randomised controlled trials comparing two doses of the same ICS in
      adults with asthma and no concomitant inhaled or oral corticosteroid were
      assessed. Included trials were analysed according to the following ICS dose
      comparisons: high (> or =800 microg/day beclomethasone (BDP)) versus moderate
      (400<800 microg/day BDP) (n = 7); moderate versus low (<400 microg/day BDP) (n =
      6); step down versus constant dose (n = 4). RESULTS: Fourteen publications
      describing 13 trials were included in the review. Studies (n = 4) that compared a
      step down approach with a constant moderate/low dose of ICS found no difference
      in lung function, symptoms, or rescue medications between the two treatment
      approaches (p>0.05). There was no difference in the change in morning peak flow
      after treatment with high compared with moderate dose ICS. When compared with low
      dose ICS, moderate dose ICS significantly improved morning peak flow (change from
      baseline WMD 11.14 l/min, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD 
      0.29, 95% CI -0.53 to -0.06). CONCLUSIONS: For patients with asthma who require
      ICS, starting with a moderate dose is equivalent to starting with a high dose and
      stepping down. The small non-significant benefits of starting with a high ICS
      dose are not of sufficient clinical benefit to warrant its use. Initial moderate
      ICS doses appear to be more effective than an initial low ICS dose.

PMID- 15563703
TI  - Asthma exacerbations in children immediately following stressful life events: a
      Cox's hierarchical regression.
AB  - BACKGROUND: A recent prospective study of children with asthma employing a within
      subject, over time analysis using dynamic logistic regression showed that
      severely negative life events significantly increased the risk of an acute
      exacerbation during the subsequent 6 week period. The timing of the maximum risk
      depended on the degree of chronic psychosocial stress also present. A
      hierarchical Cox regression analysis was undertaken to examine whether there were
      any immediate effects of negative life events in children without a background of
      high chronic stress. METHODS: Sixty children with verified chronic asthma were
      followed prospectively for 18 months with continuous monitoring of asthma by
      daily symptom diaries and peak flow measurements, accompanied by repeated
      interview assessments of life events. The key outcome measures were asthma
      exacerbations and severely negative life events. RESULTS: An immediate effect
      evident within the first 2 days following a severely negative life event
      increased the risk of a new asthma attack by a factor of 4.69, 95% confidence
      interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a
      severe event there was no increased risk of an asthma attack (p = 0.5). In
      addition to the immediate effect, an increased risk of 1.81 (95% confidence
      interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p =
      0.002). This is consistent with earlier findings. There was a statistically
      significant variation due to unobserved factors in the incidence of asthma
      attacks between the children. CONCLUSION: The use of statistical methods capable
      of investigating short time lags showed that stressful life events significantly
      increase the risk of a new asthma attack immediately after the event; a more
      delayed increase in risk was also evident 5-7 weeks later.

PMID- 15563704
TI  - Effects of asbestos and smoking on the levels and rates of change of lung
      function in a crocidolite exposed cohort in Western Australia.
AB  - BACKGROUND: Increased rates of death from asbestos related diseases have been
      reported in former workers and residents exposed to crocidolite (blue asbestos)
      at Wittenoom, Western Australia. Exposure to asbestos is associated with reduced
      static lung volumes, gas transfer and lung compliance, and a restrictive
      ventilatory abnormality. METHODS: The effects of crocidolite exposure and smoking
      history on levels and rates of change of lung function were evaluated using a
      linear mixed model. Lung function was measured as forced expiratory volume in 1
      second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: Cumulative
      doses of asbestos and the presence of radiographic asbestosis were associated
      with lower levels of FEV1 and FVC and a steeper decline during the period of
      observation. Subjects exposed to asbestos at a younger age had lower levels of
      FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung
      function than never smokers. No significant interactions between crocidolite
      exposure and smoking on the levels or rates of change of lung function were
      found. CONCLUSIONS: The deleterious effects of crocidolite exposure on lung
      function persist in this population, despite asbestos exposure having ceased more
      than 30 years ago. No significant interactions were found in this population
      between asbestos and smoking at the first visit or longitudinally.

PMID- 15563705
TI  - Protective role of metallothionein in acute lung injury induced by bacterial
      endotoxin.
AB  - BACKGROUND: Metallothionein (MT) is a protein that can be induced by inflammatory
      mediators and participate in cytoprotection. However, its role in inflammation
      remains to be established. A study was undertaken to determine whether intrinsic
      MT protects against acute inflammatory lung injury induced by bacterial endotoxin
      in MT-I/II knock out (-/-) and wild type (WT) mice. METHODS: MT (-/-) and WT mice
      were given vehicle or lipopolysaccharide (LPS, 125 microg/kg) intratracheally and
      the cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema,
      lung histology, expression of proinflammatory molecules, and nuclear localisation
      of nuclear factor-kappaB (NF-kappaB) in the lung were evaluated. RESULTS: MT (-/
      ) mice were more susceptible than WT mice to lung inflammation, especially to
      lung oedema induced by intratracheal challenge with LPS. After LPS challenge, MT
      deficiency enhanced vacuolar degeneration of pulmonary endothelial cells and type
      I alveolar epithelial cells and caused focal loss of the basement membrane. LPS
      treatment caused no significant differences in the enhanced expression of
      proinflammatory cytokines and chemokines nor in the activation of the NF-kappaB
      pathway in the lung between the two genotypes. Lipid peroxide levels in the lungs
      were significantly higher in LPS treated MT (-/-) mice than in LPS treated WT
      mice. CONCLUSIONS: Endogenous MT protects against acute lung injury related to
      LPS. The effects are possibly mediated by the enhancement of pulmonary
      endothelial and epithelial integrity, not by the inhibition of the NF-kappaB
      pathway.

PMID- 15563706
TI  - Respiratory muscle strength and the risk of incident cardiovascular events.
AB  - BACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle
      strength. The prognostic importance of MIP for cardiovascular events among
      elderly community dwelling individuals is unknown. Diminished forced vital
      capacity (FVC) is a risk factor for cardiovascular events which remains largely
      unexplained. METHODS: MIP was measured at the baseline examination of the
      Cardiovascular Health Study. Participants had to be free of prevalent congestive
      heart failure (CHF), myocardial infarction (MI), and stroke. RESULTS: Subjects in
      the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI
      1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to
      2.15) after adjustment for non-pulmonary function covariates. There was a
      potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but
      there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI
      0.93 to 1.60). The addition of FVC to models attenuated the HR associated with
      MIP only modestly; similarly, addition of MIP attenuated the HR associated with
      FVC only modestly. CONCLUSIONS: A reduced MIP is an independent risk factor for
      MI and CVD death, and a suggestion of an increased risk for stroke. This
      association with MIP appeared to be mediated through mechanisms other than
      inflammation.

PMID- 15563707
TI  - Multiple breath inert gas washout as a measure of ventilation distribution in
      children with cystic fibrosis.
AB  - BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool
      for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to
      compare the relative sensitivity of MBW and spirometry for detecting abnormal
      lung function in school age children with CF and to compare MBW results obtained
      from healthy children in the UK with those recently reported from Sweden.
      METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow
      when 25% of forced vital capacity remains to be expired (MEF25) were compared
      with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22
      children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was
      higher in children with CF than in healthy controls (mean difference 5.1 (95% CI
      of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference
      -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001
      for all). There was a significant negative correlation between LCI and FEV1 (r2 =
      0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1
      and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF,
      respectively, all but one of these children had an abnormally increased LCI. LCI
      was repeatable in both groups (within subject CV for three measurements 6% for CF
      and 5% for healthy children). In healthy subjects LCI was independent of age and
      virtually identical in the British and Swedish children (mean difference 0.1 (95%
      CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories,
      generates normal ranges which are constant over childhood, and is more frequently
      abnormal than spirometry in children with CF.

PMID- 15563708
TI  - Individualised unsupervised exercise training in adults with cystic fibrosis: a 1
      year randomised controlled trial.
AB  - BACKGROUND: Short term studies of exercise training have shown benefits in cystic
      fibrosis. Transferring exercise programmes to the community and sustaining them
      long term is a challenge for the patient. The effectiveness of an individualised
      unsupervised home based exercise programme was examined in adults with cystic
      fibrosis over a 1 year period. METHODS: Subjects were randomised to undertake
      three sessions per week of upper and lower body exercise based on individualised
      preferences (n = 30) or to a control group (n = 18). They were evaluated at
      baseline and at 12 months. The primary outcome measure was improved fitness as
      assessed by change in blood lactate concentration at the end of an identical
      constant work rate for both arm and leg ergometric testing. Secondary outcome
      measurements were heart rate and pulmonary function. RESULTS: For leg exercise,
      significant differences were seen at 12 months between the active and control
      groups in the mean (SE) change in blood lactate levels (-0.38 (0.23) mmol/l v
      0.45 (0.25) mmol/l, p<0.05) and heart rate (-4.8 (2.5) bpm v 3.4 (2.5) bpm,
      p<0.05), confirming a training effect. For arm ergometry there was no change in
      lactate levels at 12 months but there was a significant difference in forced
      vital capacity (46 (72) ml v -167 (68) ml, p<0.05). CONCLUSIONS: A training
      effect, as measured by a reduction in lactate levels and heart rate, can be
      achieved with unsupervised individualised home exercise in adults with cystic
      fibrosis. A benefit to pulmonary function was observed and together these
      findings suggest that exercise programmes should be encouraged as an important
      component of care in cystic fibrosis.

PMID- 15563709
TI  - Inflammatory response associated with pulmonary complications in non-HIV
      immunocompromised patients.
AB  - BACKGROUND: A study was undertaken to evaluate the local and systemic
      inflammatory response associated with pulmonary complications in
      immunocompromised patients and potential implications regarding severity and
      prognosis. METHODS: Levels of different inflammatory mediators were measured in
      the bronchoalveolar lavage (BAL) fluid and serum on days 1 and 4 after the
      identification of the pulmonary complication in 127 patients with different
      immunosuppressive conditions. RESULTS: Pulmonary complications were characterised
      by a high percentage of neutrophils and increased levels of tumour necrosis
      factor (TNF)-alpha, interleukin (IL)-6, IL-8 and IL-10 in the BAL fluid and high
      serum levels of TNF-alpha, IL-6, and plasma C-reactive protein (CRP). The
      inflammatory response was similar in the different groups of immunocompromised
      patients evaluated. The levels of proinflammatory cytokines were higher in
      patients with pulmonary infections, particularly those of bacterial aetiology.
      Patients with a more severe pulmonary infection had a more intense local and
      systemic inflammatory response. A BAL fluid IL-6 level of >40 pg/ml was an
      independent predictor of mortality (OR 4.65, 95% CI 1.3 to 16.1), together with a
      need for mechanical ventilation (OR 13.5, 95% CI 3.2 to 57.3). Patients who died
      had persistently high levels of CRP on day 4. CONCLUSIONS: The evaluation of the
      inflammatory response, particularly the determination of IL-6 levels in the BAL
      fluid and CRP in the serum, may be useful for deciding the appropriate management
      of pulmonary complications in immunocompromised patients.

PMID- 15563710
TI  - Sleep . 6: obstructive sleep apnoea/hypopnoea syndrome and hypertension.
AB  - The use of CPAP to control excessive daytime sleepiness in OSAHS probably also
      produces a substantial reduction in vascular risk. This is reviewed with
      particular reference to hypertension.

PMID- 15563711
TI  - Diffuse lung disease caused by cotton fibre inhalation but distinct from
      byssinosis.
AB  - A 66 year old man had inhaled cotton fibre for 50 years at his workplace. He did
      not have any respiratory symptoms. Chest CT scans revealed diffuse centrilobular
      and peribronchovascular interstitial thickening. Lung biopsy specimens confirmed
      the presence of string-like foreign bodies as well as granulomas and fibrosis in
      the peribronchial region. Infrared spectrophotometry confirmed that the foreign
      bodies were composed of natural cellulose. This is the first study to show
      directly by examination of biopsy samples that cotton fibre inhalation can cause
      diffuse lung disease. The clinical features of the disease were entirely
      different from those of byssinosis.

PMID- 15563712
TI  - Isoniazid resistant TB and non-compliance.

PMID- 15563713
TI  - B cell non-Hodgkin's lymphoma of the trachea mimicking COPD.

PMID- 15563714
TI  - Functional analysis of Drosophila beta1,4-N-acetlygalactosaminyltransferases.
AB  - Members of the mammalian beta1,4-galactosyltransferase family are among the best
      studied glycosyltransferases, but the requirements for all members of this family
      within an animal have not previously been determined. Here, we describe analysis
      of two Drosophila genes, beta4GalNAcTA (CG8536) and beta4GalNAcTB (CG14517), that
      are homologous to mammalian beta1,4-galactosyltransferases. Like their mammalian
      homologs, these glycosyltransferases use N-acetylglucosamine as an acceptor
      substrate. However, they transfer N-acetylgalactosamine rather than galactose.
      This activity, together with amino acid sequence similarity, places them among a
      group of recently identified invertebrate beta1,4-N
      acetylgalactosaminyltransferases. To investigate the biological functions of
      these genes, null mutations were generated by imprecise excision of a
      transposable element (beta4GalNAcTA) or by gene-targeted homologous recombination
      (beta4GalNAcTB). Flies mutant for beta4GalNAcTA are viable and fertile but
      display behavioral phenotypes suggestive of essential roles for GalNAc-beta1,4
      GlcNAc containing glycoconjugates in neuronal and/or muscular function.
      beta4GalNAcTB mutants are viable and display no evident morphological or
      behavioral phenotypes. Flies doubly mutant for both genes display only the
      behavioral phenotypes associated with mutation of beta4GalNAcTA. Thus Drosophila
      homologs of the mammalian beta4GalT family are essential for neuromuscular
      physiology or development but are not otherwise required for viability,
      fertility, or external morphology.

PMID- 15563715
TI  - NMR study of the preferred membrane orientation of polyisoprenols (dolichol) and
      the impact of their complex with polyisoprenyl recognition sequence peptides on
      membrane structure.
AB  - Earlier NMR studies showed that the polyisoprenols (PIs) dolichol (C95),
      dolichylphosphate (C95-P) and undecaprenylphosphate (C55-P) could alter membrane
      structure by inducing in the lamellar phospholipid (PL) bilayer a nonlamellar or
      hexagonal (Hex II) structure. The destabilizing effect of C95 and C95-P on host
      fatty acyl chains was supported by small angle X-ray diffraction and freeze
      fracture electron microscopy. Our present 1H- and 31P-NMR studies show that the
      addition of a polyisoprenol recognition sequence (PIRS) peptide to nonlamellar
      membranes induced by the PIs can reverse the hexagonal structure phase back to a
      lamellar structure. This finding shows that the PI:PIRS docking complex can
      modulate the polymorphic phase transitions in PL membranes, a finding that may
      help us better understand how glycosyl carrier-linked sugar chains may traverse
      membranes. Using an energy-minimized molecular modeling approach, we also
      determined that the long axis of C95 in phosphatidylcholine (PC) membranes is
      oriented approximately parallel to the interface of the lipid bilayer, and that
      the head and tail groups are positioned near the bilayer interior. In contrast,
      the phosphate head group of C95-P is anchored at the PC bilayer, and the angle
      between the long axis of C95-P and the bilayer interface is about 758, giving
      rise to a preferred conformation more perpendicular to the plane of the bilayer.
      Molecular modeling calculations further revealed that up to five PIRS peptides
      can bind cooperatively to a single PI molecule, and this tethered structure has
      the potential to form a membrane channel. If such a channel were to exist in
      biological membranes, it could be of functional importance in glycoconjugate
      translocation, a finding that has not been previously reported.

PMID- 15563716
TI  - Genomic haplotype blocks may not accurately reflect spatial variation in historic
      recombination intensity.
AB  - Recently, genomic data have revealed a "block-like" structure of haplotype
      diversity on human chromosomes. This structure is anticipated to facilitate gene
      mapping studies, because strong associations among loci within a block may allow
      haplotype variation to be tagged with a limited number of markers. But its
      usefulness to mapping efforts depends on the consistency of the block structure
      within and among populations, which in turn depends on how the block structure
      arises. Recombination hot spots are generally thought to underlie the block
      structure, but haplotype blocks can also develop stochastically under random
      recombination, in which case the block structure will show limited consistency
      among populations. Using coalescent models, which we upscaled to simulate the
      evolution of haplotypes with many markers at fixed distances, we show that the
      relationship between block boundaries and historic recombination intensity may be
      surprisingly weak. The majority of historic recombinations do not leave a
      footprint in present-day linkage disequilibrium patterns, and the block structure
      is sensitive to factors that affect the timing of recombination relative to
      marker mutation events in the genealogy, such as marker frequency bias and
      historic population size changes. Our results give insight into the potential of
      stochastic events to affect haplotype block structure, which can limit the
      usefulness of the block structure to mapping studies.

PMID- 15563717
TI  - Survey of simple sequence repeats in completed fungal genomes.
AB  - The use of simple sequence repeats or microsatellites as genetic markers has
      become very popular because of their abundance and length variation between
      different individuals. SSRs are tandem repeat units of 1 to 6 base pairs that are
      found abundantly in many prokaryotic and eukaryotic genomes. This is the first
      study examining and comparing SSRs in completely sequenced fungal genomes. We
      analyzed and compared the occurrences, relative abundance, relative density, most
      common, and longest SSRs in nine taxonomically different fungal species:
      Aspergillus nidulans, Cryptococcus neoformans, Encephalitozoon cuniculi, Fusarium
      graminearum, Magnaporthe grisea, Neurospora crassa, Saccharomyces cerevisiae,
      Schizosaccharomyces pombe, and Ustilago maydis. Our analysis revealed that, in
      all of the genomes studied, the occurrence, abundance, and relative density of
      SSRs varied and was not influenced by the genome sizes. No correlation between
      relative abundance and the genome sizes was observed, but it was shown that N.
      crassa, the largest genome analyzed had the highest relative abundance of SSRs.
      In most genomes, mononucleotide, dinucleotide, and trinucleotide repeats were
      more abundant than the longer repeated SSRs. Generally, in each organism, the
      occurrence, relative abundance, and relative density of SSRs decreased as the
      repeat unit increased. Furthermore, each organism had its own common and longest
      SSRs. Our analysis showed that the relative abundance of SSRs in fungi is low
      compared with the human genome and that longer SSRs in fungi are rare. In
      addition to providing new information concerning the abundance of SSRs for each
      of these fungi, the results provide a general source of molecular markers that
      could be useful for a variety of applications such as population genetics and
      strain identification of fungal organisms.

PMID- 15563718
TI  - Lack of evidence for horizontal transfer of the lac operon into Escherichia coli.
AB  - The idea that Escherichia coli gained the lac operon via horizontal transfer,
      allowing it to invade a new niche and form a new species, has become a
      paradigmatic example of bacterial nonpathogenic adaptation and speciation
      catalyzed by horizontal transfer. Surprisingly, empirical evidence for this event
      is essentially nonexistent. To see whether horizontal transfer occurred, I
      compared a phylogeny of 14 Enterobacteriaceae based on two housekeeping genes to
      a phylogeny of a part of their lac operon. Although several species in this clade
      appear to have acquired some or all of the operon via horizontal transfer, there
      is no evidence of horizontal transfer into E. coli. It is not clear whether the
      horizontal transfer events for which there is evidence were adaptive because
      those species which have acquired the operon are not thought to live in high
      lactose environments. I propose that vertical transmission from the common
      ancestor of the Enterobacteriaceae, with subsequent loss of these genes in many
      species can explain much of the patchy distribution of lactose use in this clade.
      Finally, I argue that we need new, well-supported examples of horizontal transfer
      spurring niche expansion and speciation, particularly in nonpathogenic cases,
      before we can accept claims that horizontal transfer is a hallmark of bacterial
      adaptation.

PMID- 15563719
TI  - Cocaine makes actions insensitive to outcomes but not extinction: implications
      for altered orbitofrontal-amygdalar function.
AB  - Addiction is characterized by persistent drug-seeking despite adverse
      consequences or outcomes. Such persistent behavior may result from drug-induced
      brain changes that increase the control of behavior by associations between
      antecedent cues and responses. However, it is equally plausible that brain
      changes cause a decrease in the control of behavior by the value of likely
      outcomes. To test whether drug exposure can cause persistent behavior, and to
      distinguish between these two accounts of such behavior, we tested cocaine
      experienced rats in a Pavlovian 'reinforcer devaluation' task, which provides
      independent assessments of the control of behavior by antecedent cues and outcome
      representations. We found that cocaine exposure caused persistent responding in
      this setting a month after the last drug treatment, and that this deficit
      resulted from an inability to use representations of outcome value to guide
      behavior rather than from changes in stimulus-response learning or response
      inhibition.

PMID- 15563720
TI  - Psychological structure and neural correlates of event knowledge.
AB  - Humans are capable of storing and retrieving sequences of complex structured
      events. Here we report a study in which we establish the psychological structure
      of event knowledge and then use parametric event-related functional magnetic
      resonance imaging to identify its neural correlates. We demonstrate that event
      knowledge is organized along dissociable dimensions that are reflected in
      distinctive patterns of neural activation: social valence (amygdala and right
      orbitofrontal cortex), experience (medial prefrontal cortex) and engagement (left
      orbitofrontal cortex). Our study affirms the importance and uniqueness of the
      human prefrontal cortex in representing event knowledge.

PMID- 15563721
TI  - Loss of neurofilament labeling in the primary visual cortex of monocularly
      deprived monkeys.
AB  - Visual experience during early life is important for the development of neural
      organizations that support visual function. Closing one eye (monocular
      deprivation) during this sensitive period can cause a reorganization of neural
      connections within the visual system that leaves the deprived eye functionally
      disconnected. We have assessed the pattern of neurofilament labeling in
      monocularly deprived macaque monkeys to examine the possibility that a
      cytoskeleton change contributes to deprivation-induced reorganization of neural
      connections within the primary visual cortex (V-1). Monocular deprivation for
      three months starting around the time of birth caused a significant loss of
      neurofilament labeling within deprived-eye ocular dominance columns. Three months
      of monocular deprivation initiated in adulthood did not produce a loss of
      neurofilament labeling. The evidence that neurofilament loss was found only when
      deprivation occurred during the sensitive period supports the notion that the
      loss permits restructuring of deprived-eye neural connections within the visual
      system. These results provide evidence that, in addition to reorganization of LGN
      inputs, the intrinsic circuitry of V-1 neurons is altered when monocular
      deprivation occurs early in development.

PMID- 15563722
TI  - Prefrontal-hippocampal dynamics involved in learning regularities across
      episodes.
AB  - Using functional magnetic resonance imaging, the neural correlates of context
      specific memories and invariant memories about regularities across episodes were
      investigated. Volunteers had to learn conjunctions between objects and positions.
      In an invariant learning condition, positions were held constant, enabling
      subjects to learn regularities across trials. By contrast, in a context-specific
      condition object-position conjunctions were trial unique. Performance increase in
      the invariant learning condition was paralleled by a learning-related increase of
      inferior frontal gyrus activation and ventral striatal activation and a decrease
      of hippocampus activation. Conversely, in the context-specific condition
      hippocampal activation was constant across trials. We argue that the learning
      related hippocampal activation pattern might be due to reduced relational binding
      requirements once regularities are extracted. Furthermore, we propose that the
      learning-related prefrontal modulation reflects the requirement to extract and
      maintain regularities across trials and the adjustment of object-position
      conjunctions on the basis of the extracted knowledge. Finally, our data suggest
      that the ventral striatum encodes the increased predictability of spatial
      features as a function of learning. Taken together, these results indicate a
      transition of the relative roles of distinct brain regions during learning
      regularities across multiple episodes: regularity learning is characterized by a
      shift from a hippocampal to a prefrontal-striatal brain system.

PMID- 15563723
TI  - Cross-modal integration and plastic changes revealed by lip movement, random-dot
      motion and sign languages in the hearing and deaf.
AB  - Sign language activates the auditory cortex of deaf subjects, which is evidence
      of cross-modal plasticity. Lip-reading (visual phonetics), which involves audio
      visual integration, activates the auditory cortex of hearing subjects. To test
      whether audio-visual cross-modal plasticity occurs within areas involved in cross
      modal integration, we used functional MRI to study seven prelingual deaf signers,
      10 hearing non-signers and nine hearing signers. The visually presented tasks
      included mouth-movement matching, random-dot motion matching and sign-related
      motion matching. The mouth-movement tasks included conditions with or without
      visual phonetics, and the difference between these was used to measure the lip
      reading effects. During the mouth-movement matching tasks, the deaf subjects
      showed more prominent activation of the left planum temporale (PT) than the
      hearing subjects. During dot-motion matching, the deaf showed greater activation
      in the right PT. Sign-related motion, with or without a lexical component,
      activated the left PT in the deaf signers more than in the hearing signers. These
      areas showed lip-reading effects in hearing subjects. These findings suggest that
      cross-modal plasticity is induced by auditory deprivation independent of the
      lexical processes or visual phonetics, and this plasticity is mediated in part by
      the neural substrates of audio-visual cross-modal integration.

PMID- 15563724
TI  - Population dynamics of face-responsive neurons in the inferior temporal cortex.
AB  - Neurons in the inferior temporal (IT) cortex of monkeys respond selectively to
      complex visual stimuli, such as faces. Single neurons in the IT cortex encode
      different kinds of information about visual stimuli in their temporal firing
      patterns. To understand the temporal aspects of the information encoded at a
      population level in the IT cortex, we applied principal component analysis (PCA)
      to the responses of a population of neurons. The responses of each neuron were
      recorded while visual stimuli that consisted of geometric shapes and faces of
      humans and monkeys were presented. We found that global categorization, i.e.
      human faces versus monkey faces versus shapes, occurred in the earlier part of
      the population response, and that fine categorization occurred within each member
      of the global category in the later part of the population response. A cluster
      analysis, a mixture of Gaussians analysis, confirmed that the clusters in the
      earlier part of the responses represented the global category. Moreover, the
      clusters in the earlier part separated into sub-clusters corresponding to either
      human identity or monkey expression in the later part of the responses, and the
      global categorization was maintained even after the appearance of the sub
      clusters. The results suggest that a hierarchical relationship of the test
      stimuli is represented temporally by the population response of IT neurons.

PMID- 15563725
TI  - Disturbing visual working memory: electrophysiological evidence for a role of the
      prefrontal cortex in recovery from interference.
AB  - Single cell recordings in monkeys support the notion that the lateral prefrontal
      cortex (PFC) controls reactivation of visual working memory representations when
      rehearsal is disrupted. In contrast, recent fMRI findings yielded a double
      dissociation for PFC and the medial temporal lobe (MTL) in a letter working
      memory task. PFC was engaged in interference protection during reactivation while
      MTL was prominently involved in the retrieval of the letter representations. We
      present event-related potential data (ERP) that support PFC involvement in the
      top-down control of reactivation during a visual working memory task with
      endogenously triggered recovery after visual interference. A differentiating view
      is proposed for the role of PFC in working memory with respect to
      endogenous/exogenous control and to stimulus type. General implications for
      binding and retention mechanisms are discussed.

PMID- 15563726
TI  - Specific cerebral networks for maintenance and response organization within
      working memory as evidenced by the 'double delay/double response' paradigm.
AB  - Most of the working memory (WM) tasks used in functional imaging studies are
      based on the principle of the delayed response in which both the storage and the
      response organization are present during the delay period. It is therefore
      difficult to isolate activation specific to the storage function from that
      specific to the organization of the response. To determine the specific neural
      networks associated with these two WM operations, we performed a functional MRI
      study in healthy subjects using a new paradigm, 'the double delay/double
      response' tasks. This paradigm isolates maintenance from response organization by
      dividing the delay into two separate parts, the first being dedicated to memory,
      while the second includes response organization. Activation within the
      dorsolateral prefrontal cortex (DLPFC) followed a relative hemispheric
      dissociation: activation related to maintenance was predominant in the right
      DLPFC but was only detected when the load exceeded three items. Activation
      related to response organization was predominant in the left DLPFC, regardless of
      whether this response was based on information held in WM ('memory guided') or
      was independent of WM ('visually-guided'). These results suggest that activation
      of the DLPFC, should be interpreted in terms of executive processing for both
      maintenance and response organization.

PMID- 15563727
TI  - Cortical differentiation of speech and nonspeech sounds at 100 ms: implications
      for dyslexia.
AB  - Neurophysiological measures indicate cortical sensitivity to speech sounds by 150
      ms after stimulus onset. In this time window dyslexic subjects start to show
      abnormal cortical processing. We investigated whether phonetic analysis is
      reflected in the robust auditory cortical activation at approximately 100 ms
      (N100m), and whether dyslexic subjects show abnormal N100m responses to speech or
      nonspeech sounds. We used magnetoencephalography to record auditory responses of
      10 normally reading and 10 dyslexic adults. The speech stimuli were synthetic
      Finnish speech sounds (/a/, /u/, /pa/, /ka/). The nonspeech stimuli were complex
      nonspeech sounds and simple sine wave tones, composed of the F1+F2+F3 and F2
      formant frequencies of the speech sounds, respectively. All sounds evoked a
      prominent N100m response in the bilateral auditory cortices. The N100m activation
      was stronger to speech than nonspeech sounds in the left but not in the right
      auditory cortex, in both subject groups. The leftward shift of hemispheric
      balance for speech sounds is likely to reflect analysis at the phonetic level. In
      dyslexic subjects the overall interhemispheric amplitude balance and timing were
      altered for all sound types alike. Dyslexic individuals thus seem to have an
      unusual cortical organization of general auditory processing in the time window
      of speech-sensitive analysis.

PMID- 15563728
TI  - Interhemispheric transmission of visuomotor information for motor implementation.
AB  - Using transcranial magnetic stimulation (TMS), we addressed the contribution of
      both hemispheres to the visuomotor control of each hand. The subjects had to
      press one of two buttons as quickly as possible after the go-signal. A precue
      preceding this conveyed full, partial or no advance information (hand and/or
      button), such that reaction time (RT) shortened with increasing amount of
      information. We gave TMS over each hemisphere at various time intervals (100-350
      ms) after the go-signal and before the expected onset of response, and measured
      its effect on RT, movement time (MT) and error rate. At short intervals (100-200
      ms), left hemisphere TMS delayed RT and prolonged MT of both hands, while right
      hemisphere TMS delayed RT only of the right hand, without affecting error rates.
      At long intervals (250-350 ms), TMS produced slightly more pronounced RT delays
      of the contralateral hand. RT was delayed more if the precues were less
      informative. The results suggest the importance of interhemispheric transmission
      of visuomotor information for motor implementation. The right hemisphere may play
      a role mainly in calculating target and effector information, determining RT,
      while the left hemisphere may play a role in elaborating the motor program and
      determining MT.

PMID- 15563729
TI  - Neural substrates of real and imagined sensorimotor coordination.
AB  - Much debate in the behavioral literature focuses on the relative contribution of
      motor and perceptual processes in mediating coordinative stability. To a large
      degree, such debate has proceeded independently of what is going on in the brain.
      Here, using blood oxygen level-dependent measures of neural activation, we
      compare physically executed and imagined rhythmic coordination in order to better
      assess the relative contribution of hypothesized neuromusculoskeletal mechanisms
      in modulating behavioral stability. The executed tasks were to coordinate index
      finger to thumb opposition movements of the right hand with an auditory metronome
      in either a synchronized (on the beat) or syncopated (off the beat) pattern.
      Imagination involved the same tasks, except without physical movement. Thus, the
      sensory stimulus and coordination constraints were the same in both physical and
      imagination tasks, but the motoric requirements were not. Results showed that
      neural differences between executed synchronization and syncopation found in
      premotor cortex, supplementary motor area, basal ganglia and lateral cerebellum
      persist even when the coordinative patterns were only imagined. Neural indices
      reflecting behavioral stability were not abolished by the absence of overt
      movement suggesting that coordination phenomena are not exclusively rooted in
      purely motoric constraints. On the other hand, activity in the superior temporal
      gyrus was modulated by both the presence of movement and the nature of the
      coordination, attesting to the intimacy between perceptual and motoric processes
      in coordination dynamics.

PMID- 15563730
TI  - Semenogelins I and II bind zinc and regulate the activity of prostate-specific
      antigen.
AB  - In semen, the gel proteins SgI and SgII (semenogelins I and II) are digested by
      PSA (prostate-specific antigen), resulting in liquefaction and release of motile
      spermatozoa. Semen contains a high concentration of Zn2+, which is known to
      inhibit the protease activity of PSA. We characterized the binding of Zn2+ to SgI
      and SgII and found evidence that these proteins are involved in regulating the
      activity of PSA. Intact SgI and SgII and synthetic semenogelin peptides were used
      in the experiments. Binding of Zn2+ was studied by radioligand blotting,
      titration with a zinc (II) fluorophore chelator and NMR analysis. A chromogenic
      substrate was used to measure the enzymatic activity of PSA. SgI and SgII bound
      Zn2+ with a stoichiometry of at least 10 mol (mol of protein)(-1) and with an
      average dissociation constant of approx. 5 microM per site. Moreover, Zn2+
      inhibited PSA was activated by exposure to SgI or SgII. Since both proteins have
      high affinity for Zn2+ and are the dominating proteins in semen, they probably
      represent the major Zn2+ binders in semen, one function of which may be to
      regulate the activity of PSA. The system is self-regulating, and PSA is
      maintained in an active state by its substrate.

PMID- 15563731
TI  - Immunological parameters in girls with Turner syndrome.
AB  - Disturbances in the immune system has been described in Turner syndrome, with an
      association to low levels of IgG and IgM and decreased levels of T- and B
      lymphocytes. Also different autoimmune diseases have been connected to Turner
      syndrome (45, X), thyroiditis being the most common. Besides the typical features
      of Turner syndrome (short stature, failure to enter puberty spontaneously and
      infertility due to ovarian insufficiency) ear problems are common (recurrent
      otitis media and progressive sensorineural hearing disorder). Levels of IgG, IgA,
      IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte
      subpopulations were investigated in 15 girls with Turners syndrome to examine
      whether an immunodeficiency may be the cause of their high incidence of otitis
      media. No major immunological deficiency was found that could explain the
      increased incidence of otitis media in the young Turner girls.

PMID- 15563732
TI  - Nodular osteochondrogenic activity in soft tissue surrounding osteoma in
      neurogenic para osteo-arthropathy: morphological and immunohistochemical study.
AB  - BACKGROUND: Neurogenic Para-Osteo-Arthropathy (NPOA) occurs as a consequence of
      central nervous system injuries or some systemic conditions. They are
      characterized by bone formation around the main joints. METHODS: In order to
      define some biological features of NPOAs, histological and immunohistological
      studies of the soft tissue surrounding osteoma and Ultrasound examination (US) of
      NPOA before the appearance of abnormal ossification on plain radiographs were
      performed. RESULTS: We have observed a great number of ossifying areas scattered
      in soft tissues. US examination have also shown scattered ossifying areas at the
      early stage of ossification. A high osteogenic activity was detected in these
      tissues and all the stages of the endochondral process were observed. Mesenchymal
      cells undergo chondrocytic differentiation to further terminal maturation with
      hypertrophy, which sustains mineralization followed by endochondral ossification
      process. CONCLUSION: We suggest that periosteoma soft tissue reflect early stage
      of osteoma formation and could be a model to study the mechanism of osteoma
      formation and we propose a mechanism of the NPOA formation in which sympathetic
      dystony and altered mechanical loading induce changes which could be responsible
      for the cascade of cellular events leading to cartilage and bone formation.

PMID- 15563733
TI  - Single-track sequencing for genotyping of multiple SNPs in the N
      acetyltransferase 1 (NAT1) gene.
AB  - BACKGROUND: Fast, cheap and reliable methods are needed to identify large
      populations, which may be at risk in relation to environmental exposure.
      Polymorphisms in NAT1 (N-acetyl transferase) may be suitable markers to identify
      individuals at risk. RESULTS: A strategy allowing to address simultaneously 24
      various genetic variants in the NAT1 gene using the single sequencing reaction
      method on the same PCR product is described. A modified automated DNA sequencing
      using only one of the sequence terminators was used to genotype PCR products in
      single-track sequencing reactions of NAT1 and was shown to be universal for both
      DNA sequencing using labeled primers and labeled nucleotides. By this method we
      detected known SNPs at site T640G, which confers the NAT1*11 allele with
      frequency of 0.036, further T1088A and C1095A with frequency of 0.172 and 0.188,
      respectively and a deletion of TAATAATAA in the poly A signal area with a
      frequency 0.031. All observed frequencies were in Hardy Weinberg equilibrium and
      comparable to those in Caucasian population. The single-track signatures of the
      variant genotypes were verified on samples previously genotyped by RLFP.
      CONCLUSIONS: The method could be of great help to scientists in the field of
      molecular epidemiology of screening of large populations for known informative
      biomarkers of susceptibility, such as NAT1.

PMID- 15563734
TI  - Protein family comparison using statistical models and predicted structural
      information.
AB  - BACKGROUND: This paper presents a simple method to increase the sensitivity of
      protein family comparisons by incorporating secondary structure (SS) information.
      We build upon the effective information theory approach towards profile-profile
      comparison described in [Yona & Levitt 2002]. Our method augments profile columns
      using PSIPRED secondary structure predictions and assesses statistical similarity
      using information theoretical principles. RESULTS: Our tests show that this tool
      detects more similarities between protein families of distant homology than the
      previous primary sequence-based method. A very significant improvement in
      performance is observed when the real secondary structure is used. CONCLUSIONS:
      Integration of primary and secondary structure information can substantially
      improve detection of relationships between remotely related protein families.

PMID- 15563735
TI  - A quantitative comparison of different methods to detect cardiorespiratory
      coordination during night-time sleep.
AB  - BACKGROUND: The univariate approaches used to analyze heart rate variability have
      recently been extended by several bivariate approaches with respect to
      cardiorespiratory coordination. Some approaches are explicitly based on
      mathematical models which investigate the synchronization between weakly coupled
      complex systems. Others use an heuristic approach, i.e. characteristic features
      of both time series, to develop appropriate bivariate methods. OBJECTIVE: In this
      study six different methods used to analyze cardiorespiratory coordination have
      been quantitatively compared with respect to their performance (no. of sequences
      with cardiorespiratory coordination, no. of heart beats coordinated with
      respiration). Five of these approaches have been suggested in the recent
      literature whereas one method originates from older studies. RESULTS: The methods
      were applied to the simultaneous recordings of an electrocardiogram and a
      respiratory trace of 20 healthy subjects during night-time sleep from 0:00 to
      6:00. The best temporal resolution and the highest number of coordinated heart
      beats were obtained with the analysis of 'Phase Recurrences'. Apart from the
      oldest method, all methods showed similar qualitative results although the
      quantities varied between the different approaches. In contrast, the oldest
      method detected considerably fewer coordinated heart beats since it only used
      part of the maximum amount of information available in each recording.
      CONCLUSIONS: The method of 'Phase Recurrences' should be the method of choice for
      the detection of cardiorespiratory coordination since it offers the best temporal
      resolution and the highest number of coordinated sequences and heart beats.
      Excluding the oldest method, the results of the heuristic approaches may also be
      interpreted in terms of the mathematical models.

PMID- 15563736
TI  - 16S rRNA gene based analysis of Enterobacter sakazakii strains from different
      sources and development of a PCR assay for identification.
AB  - BACKGROUND: E. sakazakii is considered to be an opportunistic pathogen,
      implicated in food borne diseases causing meningitis or enteritis especially in
      neonates and infants. Cultural standard identification procedures for E.
      sakazakii include the observation of yellow pigmentation of colonies and a
      positive glucosidase activity. Up to now, only one PCR system based on a single
      available 16S rRNA gene sequence has been published for E. sakazakii
      identification. However, in our hands a preliminary evaluation of this system to
      a number of target and non-target strains showed significant specificity problems
      of this system. In this study full-length 16S rRNA genes of thirteen E. sakazakii
      strains from food, environment and human origin as well as the type strain ATCC
      51329 were sequenced. Based on this sequence data a new specific PCR system for
      E. sakazakii was developed and evaluated. RESULTS: By phylogenetic analysis of
      the new full-length 16S rRNA gene sequence data obtained we could show the
      presence of a second phylogenetic distinct lineage within the E. sakazakii
      species. The newly developed 16S rRNA gene targeting PCR system allows
      identification of E. sakazakii strains from both lineages. The assay's ability to
      correctly identify different E. sakazakii isolates as well as to differentiate E.
      sakazakii from other closely related Enterobacteriaceae species and other
      microorganisms was shown on 75 target and non-target strains. CONCLUSION: By this
      study we are presenting a specific and reliable PCR identification system, which
      is able to correctly identify E. sakazakii isolates from both phylogenetic
      distinct lines within the E. sakazakii species. The impact of this second newly
      described phylogenetic line within the E. sakazakii species in view of clinical
      and food safety aspects need further investigation.

PMID- 15563737
TI  - Context-dependent selection of visuomotor maps.
AB  - BACKGROUND: Behavior results from the integration of ongoing sensory signals and
      contextual information in various forms, such as past experience, expectations,
      current goals, etc. Thus, the response to a specific stimulus, say the ringing of
      a doorbell, varies depending on whether you are at home or in someone else's
      house. What is the neural basis of this flexibility? What mechanism is capable of
      selecting, in a context-dependent way an adequate response to a given stimulus?
      One possibility is based on a nonlinear neural representation in which context
      information regulates the gain of stimulus-evoked responses. Here I explore the
      properties of this mechanism. RESULTS: By means of three hypothetical visuomotor
      tasks, I study a class of neural network models in which any one of several
      possible stimulus-response maps or rules can be selected according to context.
      The underlying mechanism based on gain modulation has three key features: (1)
      modulating the sensory responses is equivalent to switching on or off different
      subpopulations of neurons, (2) context does not need to be represented
      continuously, although this is advantageous for generalization, and (3) context
      dependent selection is independent of the discriminability of the stimuli. In all
      cases, the contextual cues can quickly turn on or off a sensory-motor map,
      effectively changing the functional connectivity between inputs and outputs in
      the networks. CONCLUSIONS: The modulation of sensory-triggered activity by
      proprioceptive signals such as eye or head position is regarded as a general
      mechanism for performing coordinate transformations in vision. The present
      results generalize this mechanism to situations where the modulatory quantity and
      the input-output relationships that it selects are arbitrary. The model predicts
      that sensory responses that are nonlinearly modulated by arbitrary context
      signals should be found in behavioral situations that involve choosing or
      switching between multiple sensory-motor maps. Because any relevant
      circumstancial information can be part of the context, this mechanism may partly
      explain the complex and rich behavioral repertoire of higher organisms.

PMID- 15563738
TI  - The role of transforming growth factor-beta (TGF-beta) during ovarian follicular
      development in sheep.
AB  - BACKGROUND: Recently, several members of the transforming growth factor-beta (TGF
      beta) superfamily have been shown to be essential for regulating the growth and
      differentiation of ovarian follicles and thus fertility. METHODS: Ovaries of
      neonatal and adult sheep were examined for expression of the TGF-betas 1-3 and
      their receptors (RI and RII) by in situ hybridization using ovine cDNAs. The
      effects of TGF-beta 1 and 2 on proliferation and differentiation of ovine
      granulosa cells in vitro were also studied. RESULTS: The expression patterns of
      TGF-beta 1 and 2 were similar in that both mRNAs were first observed in thecal
      cells of type 3 (small pre-antral) follicles. Expression of both mRNAs continued
      to be observed in the theca of larger follicles and was also present in cells
      within the stroma and associated with the vascular system of the ovary. There was
      no evidence for expression in granulosa cells or oocytes. Expression of TGF-beta
      3 mRNA was limited to cells associated with the vascular system within the ovary.
      TGFbetaRI mRNA was observed in oocytes from the type 1 (primordial) to type 5
      (antral) stages of follicular growth and granulosa and thecal cells expressed
      this mRNA at the type 3 (small pre-antral) and subsequent stages of development.
      The TGFbetaRI signal was also observed in the ovarian stroma and vascular cells.
      In ovarian follicles, mRNA encoding TGFbetaRII was restricted to thecal cells of
      type 3 (small pre-antral) and larger follicles. In addition, expression was also
      observed in some cells of the surface epithelium and in some stromal cells. In
      granulosa cells cultured for 6 days, both TGF-beta 1 and 2 decreased, in a dose
      dependent manner, both the amount of DNA and concentration of progesterone.
      CONCLUSION: In summary, mRNA encoding both TGF-beta 1 and 2 were synthesized by
      ovarian theca, stroma and cells of the vascular system whereas TGF-beta 3 mRNA
      was synthesized by vascular cells. Luteinizing granulosa cells also responded to
      both TGF-beta 1 and beta 2 in vitro. These findings in sheep are consistent with
      TGF-beta potentially being an important autocrine regulator of thecal cell
      function and possibly a paracrine regulator of ovarian cell function at various
      development stages.

PMID- 15563739
TI  - Melatonin blocks inhibitory effects of prolactin on photoperiodic induction of
      gain in body mass, testicular growth and feather regeneration in the migratory
      male redheaded bunting (Emberiza bruniceps).
AB  - Little is known about how hormones interact in the photoperiodic induction of
      seasonal responses in birds. In this study, two experiments determined if the
      treatment with melatonin altered inhibitory effects of prolactin on photoperiodic
      induction of seasonal responses in the Palearctic-Indian migratory male redheaded
      bunting Emberiza bruniceps. Each experiment employed three groups (N = 6-7 each)
      of photosensitive birds that were held under 8 hours light: 16 hours darkness
      (8L:16D) since early March. In the experiment 1, beginning in mid June 2001,
      birds were exposed to natural day lengths (NDL) at 27 degree North (day length =
      ca.13.8 h, sunrise to sunset) for 23 days. In the experiment 2, beginning in
      early April 2002, birds were exposed to 14L:10D for 22 days. Beginning on day 4
      of NDL or day 1 of 14L:10D, they received 10 (experiment 1) or 13 (experiment 2)
      daily injections of both melatonin and prolactin (group 1) or prolactin alone
      (group 2) at a dose of 20 microgram per bird per day in 200 microliter of
      vehicle. Controls (group 3) received similar volume of vehicle. Thereafter, birds
      were left uninjected for the next 10 (experiment 1) or 9 days (experiment 2). All
      injections except those of melatonin were made at the zeitgeber time 10 (ZT 0 =
      time of sunrise, experiment 1; time of lights on, experiment 2); melatonin was
      injected at ZT 9.5 and thus 0.5 h before prolactin. Observations were recorded on
      changes in body mass, testicular growth and feather regeneration. Under NDL
      (experiment 1), testis growth in birds that received melatonin 0.5 h prior to
      prolactin (group 1) was significantly greater (P < 0.05, Student Newman-Keuls
      test) than in those birds that received prolactin alone (group 2) or vehicle
      (group 3). Although mean body mass of three groups were not significantly
      different at the end of the experiment, the regeneration of papillae was
      dramatically delayed in prolactin only treated group 2 birds. Similarly, under
      14L:10D (experiment 2) testes of birds receiving melatonin plus prolactin (group
      1) and vehicle (group 3) were significantly larger (P < 0.05, Student Newman
      Keuls test) than those receiving prolactin alone (group 2). Also, birds of groups
      1 and 3, but not of group 2, had significant (P < 0.05, 1-way repeated measures
      Analysis of Variance) gain in body mass. However, unlike in the experiment 1, the
      feather regeneration in birds of the three groups was not dramatically different;
      a relatively slower rate of papillae emergence was however noticed in group 2
      birds. Considered together, these results show that a prior treatment with
      melatonin blocks prolactin-induced suppression of photoperiodic induction in the
      redheaded bunting, and suggest an indirect role of melatonin in the regulation of
      seasonal responses of birds.

PMID- 15563740
TI  - Introduction: chronic pain studies of the lidocaine patch 5% using the
      Neuropathic Pain Scale.
AB  - The manifestation of pain in any individual patient may result from a variety of
      underlying mechanisms that also may vary from one disease state to another.
      Global measures of pain intensity and relief are inadequate for characterizing
      specific pain qualities or identifying the unique effects of pain treatments on
      different pain qualities. The Neuropathic Pain Scale (NPS) is a recently
      developed measure designed to assess distinct pain qualities and may allow
      differentiation of therapeutic effects, even in cases where global pain response
      may be similar. Three studies are presented that provide preliminary evidence for
      the utility of the NPS for characterizing distinct pain qualities and changes in
      pain qualities in patients treated with the lidocaine patch 5% for a variety of
      neuropathic and non-neuropathic chronic pain conditions, including low-back pain,
      osteoarthritis, post-herpetic neuralgia, and painful diabetic neuropathy.

PMID- 15563741
TI  - Use of the lidocaine patch 5% in reducing intensity of various pain qualities
      reported by patients with low-back pain.
AB  - OBJECTIVE: To determine the impact of the lidocaine patch 5% on pain qualities
      associated with low-back pain (LBP) through use of the Neuropathic Pain Scale
      (NPS). PATIENTS AND METHODS: Patients were enrolled in an open-label, non
      randomized, prospective, 6-week study involving 8 clinical trial sites in the
      United States. Eligible patients had non-radicular LBP and reported moderate-to
      severe pain on the NPS at study enrollment. Patients were stratified to 3 groups
      based on the duration of their LBP, defined as acute/sub-acute (< 3 months),
      short-term chronic (3-12 months), or long-term chronic LBP (> 12 months). The
      lidocaine patch 5% was applied to the area of maximal pain, using no more than a
      total of 4 patches changed every 24 h. Effectiveness was measured by change from
      baseline to Week 2 and Week 6 in 4 composite measures of the NPS: NPS-10, NPS-4,
      NPS-8, and NPS-non-allodynia. Safety was assessed by adverse events (AEs), dermal
      assessment of application site(s), and skin sensory testing. RESULTS: In the
      combined patient population (n = 71), 6 weeks of treatment with lidocaine patch
      5% significantly improved all 4 NPS composite measures at both Week 2 and Week 6
      (p < 0.001). Separate analyses by subgroups revealed differential improvements in
      the 4 composite measures. Eleven patients (15.5%) experienced treatment-related
      AEs that were primarily mild-to-moderate and dermal in nature. CONCLUSIONS: In
      patients with moderate-to-severe LBP, 2 weeks and 6 weeks of treatment with the
      lidocaine patch 5% significantly reduces the intensity of pain qualities as
      measured by all 4 NPS composite measures. Lidocaine patch 5% is well tolerated
      with few systemic AEs and may provide beneficial pain relief for patients
      receiving multidisciplinary treatment without increasing risks for adverse drug
      interactions. Pain scales such as the NPS offer the ability to measure various
      pain qualities experienced by LBP patients and may allow clinicians to assess the
      treatment impact of different medications.

PMID- 15563742
TI  - Lidocaine patch 5% and its positive impact on pain qualities in osteoarthritis:
      results of a pilot 2-week, open-label study using the Neuropathic Pain Scale.
AB  - OBJECTIVE: To determine the impact of the lidocaine patch 5% on distinct pain
      qualities associated with osteoarthritis (OA) through use of the Neuropathic Pain
      Scale (NPS), an assessment tool designed to assess intensity of various pain
      qualities (i.e.sharp, dull). PATIENTS AND METHODS: Patients were enrolled in a
      prospective, open-label, non-randomized, parallel-group, 2-week study involving 8
      clinical trial sites in the United States. Eligible patients had radiographic
      evidence of OA involving one or both knees and reported moderate-to-severe pain
      (despite prn or stable doses of analgesics) on the NPS at study enrollment.
      Patients on prn analgesics were discontinued from all analgesic regimens prior to
      study entry and received lidocaine patch 5% as monotherapy. Those on stable doses
      of analgesics were continued on their other analgesic regimens with no additions
      or dose alterations allowed other than the lidocaine patch 5% as add-on therapy.
      The lidocaine patch 5% was applied to the area of maximal pain, using no more
      than a total of 4 patches changed every 24 h. Effectiveness was measured by
      change from baseline to Week 2 in 4 composite measures of the NPS: NPS-10, NPS-4,
      NPS-8, and NPS-nonallodynia. Safety was assessed by adverse events (AEs), dermal
      assessment of application site(s), and skin sensory testing. RESULTS: In the
      combined patient population (n = 100), 2 weeks of treatment with lidocaine patch
      5% significantly improved all 4 NPS composite measures (p < 0.001). Separate
      analyses by subgroups revealed significant improvements in all 4 composite
      measures for both the monotherapy group (n = 12; p < 0.01) and add-on therapy
      group (n = 88; p < 0.001). No treatment-related AEs were reported for the
      monotherapy group. In the add-on therapy group, 5 patients experienced mild-to
      moderate treatment-related AEs. CONCLUSIONS: In patients with moderate-to-severe
      OA of the knee, 2 weeks of treatment with the lidocaine patch 5% significantly
      reduces the intensity of pain qualities as measured by all 4 NPS composite
      measures. Our results coincide with previously reported improvements in pain and
      physical function in the same patient population, as measured by the Western
      Ontario and McMaster Universities OA Index. Measuring the various qualities of
      pain appears to be a valid approach for assessing clinical outcomes in the
      treatment of OA pain. Pain measures such as the NPS can capture the multi
      dimensional properties of a patient's pain experience and may offer clinicians
      the possibility to identify differential effects of analgesic treatments on
      various pain qualities associated with OA.

PMID- 15563743
TI  - Effectiveness of the lidocaine patch 5% on pain qualities in three chronic pain
      states: assessment with the Neuropathic Pain Scale.
AB  - OBJECTIVE: To determine the impact of the lidocaine patch 5% on pain qualities
      associated with chronic pain from postherpetic neuralgia (PHN), painful diabetic
      neuropathy (DN), and low-back pain (LBP), using the Neuropathic Pain Scale (NPS).
      PATIENTS AND METHODS: Patients with PHN, painful DN, and LBP were enrolled if
      they had partial response to gabapentin-containing analgesic regimens and if they
      reported moderate-to-severe pain on the NPS at study enrollment. Eligible
      patients were included in an open-label, non-randomized, prospective, 2-week
      study across 7 clinical trial sites in the United States. The lidocaine patch 5%
      was applied to the area of maximal pain, using no more than a total of 4 patches
      changed every 24 h. Patients were maintained on their other analgesic regimens
      with no dose adjustment or additions allowed. Treatment effect was measured by
      change from baseline to Week 2 in 4 composite measures of the NPS: NPS-10, NPS-4,
      NPS-8, and NPS-non-allodynia. Safety was assessed by adverse events (AEs), dermal
      assessment of application site(s), and skin sensory testing. RESULTS: In the
      combined patient population (n = 77), 2 weeks of treatment with the lidocaine
      patch 5% significantly improved all 4 composite measures (p < 0.01). In the
      subgroup analyses, the lidocaine patch 5% demonstrated numerical advantage for
      all 4 NPS composite measures for the PHN patients (n = 8), and significantly
      improved all 4 composite measures for the painful DN patients (n = 41; p < 0.001)
      and LBP patients (n = 28; p < or = 0.005). Overall, 8 patients (10%) experienced
      mild-to-moderate treatment-related AEs. CONCLUSIONS: The lidocaine patch 5%
      effectively reduces the intensity of all common pain qualities in patients with
      moderate-to-severe chronic pain resulting from PHN, painful DN, or LBP. Treatment
      is well tolerated in combination with other analgesic regimens, with no reports
      of serious AEs or adverse drug interactions. Assessment scales such as the NPS
      may offer the possibility to differentiate between various pain states and to
      assess treatment outcomes for various pain qualities associated with a given pain
      state.

PMID- 15563744
TI  - Conclusions: chronic pain studies of lidocaine patch 5% using the Neuropathic
      Pain Scale.
AB  - Many chronic pain patients have multiple etiologies for their pain, and accurate
      characterization of pain qualities and pain relief is essential for managing
      their pain. The ability to utilize a validated tool for assessing pain qualities
      and for identifying unique analgesic therapy effects on different pain qualities
      may assist clinicians in devising an appropriate treatment regimen. The
      Neuropathic Pain Scale (NPS) is a novel pain metric for characterizing pain in 10
      dimensions. The ability to differentiate among pain qualities for each patient
      may result in a more refined and effective choice of therapy. The three research
      articles in this Supplement demonstrate the utility of the NPS in chronic pain
      patients treated with the lidocaine patch 5%, a peripherally acting medication
      that is not associated with systemic accumulation of the active drug. Significant
      reduction in the intensity of commonly reported pain qualities in patients with
      neuropathic and non-neuropathic chronic pain due to low-back pain,
      osteoarthritis, post-herpetic neuralgia, and painful diabetic neuropathy were
      achieved. The NPS offers clinicians a reliable means to accurately identify pain
      qualities associated with each individual patient and to target and assess the
      efficacy of various therapeutic options on those pain components. Utilizing the
      NPS, the lidocaine patch 5% was effective in treating chronic pain of both
      neuropathic and non-neuropathic origins suggesting that a given treatment's
      effect on various pain qualities may be consistent across pain types.

PMID- 15563746
TI  - Efficient coding of time-relative structure using spikes.
AB  - Nonstationary acoustic features provide essential cues for many auditory tasks,
      including sound localization, auditory stream analysis, and speech recognition.
      These features can best be characterized relative to a precise point in time,
      such as the onset of a sound or the beginning of a harmonic periodicity.
      Extracting these types of features is a difficult problem. Part of the difficulty
      is that with standard block-based signal analysis methods, the representation is
      sensitive to the arbitrary alignment of the blocks with respect to the signal.
      Convolutional techniques such as shift-invariant transformations can reduce this
      sensitivity, but these do not yield a code that is efficient, that is, one that
      forms a nonredundant representation of the underlying structure. Here, we develop
      a non-block-based method for signal representation that is both time relative and
      efficient. Signals are represented using a linear superposition of time-shiftable
      kernel functions, each with an associated magnitude and temporal position. Signal
      decomposition in this method is a non-linear process that consists of optimizing
      the kernel function scaling coefficients and temporal positions to form an
      efficient, shift-invariant representation. We demonstrate the properties of this
      representation for the purpose of characterizing structure in various types of
      nonstationary acoustic signals. The computational problem investigated here has
      direct relevance to the neural coding at the auditory nerve and the more general
      issue of how to encode complex, time-varying signals with a population of spiking
      neurons.

PMID- 15563747
TI  - Bilinear sparse coding for invariant vision.
AB  - Recent algorithms for sparse coding and independent component analysis (ICA) have
      demonstrated how localized features can be learned from natural images. However,
      these approaches do not take image transformations into account. We describe an
      unsupervised algorithm for learning both localized features and their
      transformations directly from images using a sparse bilinear generative model. We
      show that from an arbitrary set of natural images, the algorithm produces
      oriented basis filters that can simultaneously represent features in an image and
      their transformations. The learned generative model can be used to translate
      features to different locations, thereby reducing the need to learn the same
      feature at multiple locations, a limitation of previous approaches to sparse
      coding and ICA. Our results suggest that by explicitly modeling the interaction
      between local image features and their transformations, the sparse bilinear
      approach can provide a basis for achieving transformation-invariant vision.

PMID- 15563748
TI  - A probabilistic framework for region-specific remodeling of dendrites in three
      dimensional neuronal reconstructions.
AB  - Dendritic arborization is an important determinant of single-neuron function as
      well as the circuitry among neurons. Dendritic trees undergo remodeling during
      development, aging, and many pathological conditions, with many of the
      morphological changes being confined to certain regions of the dendritic tree. In
      order to analyze the functional consequences of such region-specific dendritic
      remodeling, it is essential to develop techniques that can systematically
      manipulate three-dimensional reconstructions of neurons. Hence, in this study, we
      develop an algorithm that uses statistics from precise morphometric analyses to
      systematically remodel neuronal reconstructions. We use the distribution function
      of the ratio of two normal distributed random variables to specify the
      probabilities of remodeling along various regions of the dendritic arborization.
      We then use these probabilities to drive an iterative algorithm for manipulating
      the dendritic tree in a region-specific manner. As a test, we apply this
      framework to a well-characterized example of dendritic remodeling: stress-induced
      dendritic atrophy in hippocampal CA3 pyramidal cells. We show that our pruning
      algorithm is capable of eliciting atrophy that matches biological data from
      rodent models of chronic stress.

PMID- 15563749
TI  - Analysis of cyclic dynamics for networks of linear threshold neurons.
AB  - The network of neurons with linear threshold (LT) transfer functions is a
      prominent model to emulate the behavior of cortical neurons. The analysis of
      dynamic properties for LT networks has attracted growing interest, such as
      multistability and boundedness. However, not much is known about how the
      connection strength and external inputs are related to oscillatory behaviors.
      Periodic oscillation is an important characteristic that relates to
      nondivergence, which shows that the network is still bounded although unstable
      modes exist. By concentrating on a general parameterized two-cell network,
      theoretical results for geometrical properties and existence of periodic orbits
      are presented. Although it is restricted to two-dimensional systems, the analysis
      can provide a useful contribution to analyze cyclic dynamics of some specific LT
      networks of high dimension. As an application, it is extended to an important
      class of biologically motivated networks of large scale: the winner-take-all
      model using local excitation and global inhibition.

PMID- 15563750
TI  - Nonlinear and noisy extension of independent component analysis: theory and its
      application to a pitch sensation model.
AB  - In this letter, we propose a noisy nonlinear version of independent component
      analysis (ICA). Assuming that the probability density function (p. d. f.) of
      sources is known, a learning rule is derived based on maximum likelihood
      estimation (MLE). Our model involves some algorithms of noisy linear ICA (e. g.,
      Bermond & Cardoso, 1999) or noise-free nonlinear ICA (e. g., Lee, Koehler, &
      Orglmeister, 1997) as special cases. Especially when the nonlinear function is
      linear, the learning rule derived as a generalized expectation-maximization
      algorithm has a similar form to the noisy ICA algorithm previously presented by
      Douglas, Cichocki, and Amari (1998). Moreover, our learning rule becomes
      identical to the standard noise-free linear ICA algorithm in the noiseless limit,
      while existing MLE-based noisy ICA algorithms do not rigorously include the noise
      free ICA. We trained our noisy nonlinear ICA by using acoustic signals such as
      speech and music. The model after learning successfully simulates virtual pitch
      phenomena, and the existence region of virtual pitch is qualitatively similar to
      that observed in a psychoacoustic experiment. Although a linear transformation
      hypothesized in the central auditory system can account for the pitch sensation,
      our model suggests that the linear transformation can be acquired through
      learning from actual acoustic signals. Since our model includes a cepstrum
      analysis in a special case, it is expected to provide a useful feature extraction
      method that has often been given by the cepstrum analysis.

PMID- 15563751
TI  - Online ranking by projecting.
AB  - We discuss the problem of ranking instances. In our framework, each instance is
      associated with a rank or a rating, which is an integer in 1 to k. Our goal is to
      find a rank-prediction rule that assigns each instance a rank that is as close as
      possible to the instance's true rank. We discuss a group of closely related
      online algorithms, analyze their performance in the mistake-bound model, and
      prove their correctness. We describe two sets of experiments, with synthetic data
      and with the EachMovie data set for collaborative filtering. In the experiments
      we performed, our algorithms outperform online algorithms for regression and
      classification applied to ranking.

PMID- 15563752
TI  - On learning vector-valued functions.
AB  - In this letter, we provide a study of learning in a Hilbert space of vectorvalued
      functions. We motivate the need for extending learning theory of scalar-valued
      functions by practical considerations and establish some basic results for
      learning vector-valued functions that should prove useful in applications.
      Specifically, we allow an output space Y to be a Hilbert space, and we consider a
      reproducing kernel Hilbert space of functions whose values lie in Y. In this
      setting, we derive the form of the minimal norm interpolant to a finite set of
      data and apply it to study some regularization functionals that are important in
      learning theory. We consider specific examples of such functionals corresponding
      to multiple-output regularization networks and support vector machines, for both
      regression and classification. Finally, we provide classes of operator-valued
      kernels of the dot product and translation-invariant type.

PMID- 15563753
TI  - RSPOP: rough set-based pseudo outer-product fuzzy rule identification algorithm.
AB  - System modeling with neuro-fuzzy systems involves two contradictory requirements:
      interpretability verses accuracy. The pseudo outer-product (POP) rule
      identification algorithm used in the family of pseudo outer-product-based fuzzy
      neural networks (POPFNN) suffered from an exponential increase in the number of
      identified fuzzy rules and computational complexity arising from high-dimensional
      data. This decreases the interpretability of the POPFNN in linguistic fuzzy
      modeling. This article proposes a novel rough set-based pseudo outer-product
      (RSPOP) algorithm that integrates the sound concept of knowledge reduction from
      rough set theory with the POP algorithm. The proposed algorithm not only performs
      feature selection through the reduction of attributes but also extends the
      reduction to rules without redundant attributes. As many possible reducts exist
      in a given rule set, an objective measure is developed for POPFNN to correctly
      identify the reducts that improve the inferred consequence. Experimental results
      are presented using published data sets and real-world application involving
      highway traffic flow prediction to evaluate the effectiveness of using the
      proposed algorithm to identify fuzzy rules in the POPFNN using compositional rule
      of inference and singleton fuzzifier (POPFNN-CRI(S)) architecture. Results showed
      that the proposed rough set-based pseudo outer-product algorithm reduces
      computational complexity, improves the interpretability of neuro-fuzzy systems by
      identifying significantly fewer fuzzy rules, and improves the accuracy of the
      POPFNN.

PMID- 15563754
TI  - Targeting beta-cell cyclic 3'5' adenosine monophosphate for the development of
      novel drugs for treating type 2 diabetes mellitus. A review.
AB  - Cyclic 3'5'AMP is an important physiological amplifier of glucose-induced insulin
      secretion by the pancreatic islet beta-cell, where it is formed by the activity
      of adenylyl cyclase, especially in response to the incretin hormones GLP-1
      (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide).
      These hormones are secreted from the small intestine during and following a meal,
      and are important in producing a full insulin secretory response to nutrient
      stimuli. Cyclic AMP influences many steps involved in glucose-induced insulin
      secretion and may be important in regulating pancreatic islet beta-cell
      differentiation, growth and survival. Cyclic AMP (cAMP) itself is rapidly
      degraded in the pancreatic islet beta-cell by cyclic nucleotide phosphodiesterase
      (PDE) enzymes. This review discusses the possibility of targeting cAMP mechanisms
      in the treatment of type 2 diabetes mellitus, in which insulin release in
      response to glucose is impaired. This could be achieved by the use of GLP-1 or
      GIP to elevate cAMP in the pancreatic islet beta-cell. However, these peptides
      are normally rapidly degraded by dipeptidyl peptidase IV (DPP IV). Thus longer
      acting analogues of GLP-1 and GIP, resistant to enzymic degradation, and orally
      active inhibitors of DPP IV have also been developed, and these agents were found
      to improve metabolic control in experimentally diabetic animals and in patients
      with type 2 diabetes. The use of selective inhibitors of type 3 phosphodiesterase
      (PDE3B), which is probably the important pancreatic islet beta-cell PDE isoform,
      would require their targeting to the islet beta-cell, because inhibition of PDE3B
      in adipocytes and hepatocytes would induce insulin resistance.

PMID- 15563755
TI  - Development and evaluation of the essential oil from Magnolia fargesii for
      enhancing the transdermal absorption of theophylline and cianidanol.
AB  - To improve the skin permeation of theophylline and cianidanol ((+)-catechin), the
      essential oil of Magnolia fargesii was evaluated using in-vitro and in-vivo
      permeation techniques. Oxygenated monoterpenes and sesquiterpenes are the major
      components of M. fargesii essential oil. The in-vitro permeation of theophylline
      and cianidanol was significantly enhanced after treatment with M. fargesii
      essential oil. The essential oil increased the in-vivo skin deposition of
      cianidanol but not theophylline. On the other hand, in-vivo microdialysis showed
      a higher subcutaneous theophylline amount after essential oil treatment. In-vitro
      cell viability and prostaglandin E(2) release by skin keratinocytes indicated
      that there was low or negligible cytotoxicity by M. fargesii essential oil. The
      in-vivo skin tolerance study determined by transepidermal water loss and
      colorimetry confirmed that no irritation of the skin was detected when using M.
      fargesii essential oil.

PMID- 15563756
TI  - Determination of diffusion coefficients of peptides and prediction of
      permeability through a porous membrane.
AB  - The diffusion coefficient (D) of peptide and protein drugs needs to be determined
      to examine the permeability through biological barriers and to optimize delivery
      systems. In this study, the D values of fluorescein isothiocyanate (FITC)
      labelled dextrans (FDs) and peptides were determined and the permeability through
      a porous membrane was discussed. The observed D values of FDs and peptides,
      except in the case of insulin, were similar to those calculated based on a
      relationship previously reported between the molecular weight and D of lower
      molecular-weight compounds, although the molecular weight range was completely
      different. The observed D value of insulin was between the calculated values for
      the insulin monomer and hexamer. The permeability of poly-lysine and insulin
      through the membrane was determined and the observed values were compared with
      predicted values by using the relationship between molecular weight and D and an
      equation based on the Renkin function. The observed permeability of insulin
      through the membrane was between that of the predicted permeability for the
      insulin monomer and hexamer. For the permeation of insulin, the determination of
      D was useful for estimating the permeability because of the irregular
      relationship between molecular weight and D. The methodology used in this study
      will be useful for a more quantitative evaluation of the absorption of peptide
      and protein drugs applied to mucous membranes.

PMID- 15563757
TI  - Development of a topical niosomal preparation of acetazolamide: preparation and
      evaluation.
AB  - Orally administered acetazolamide has a limited use in glaucoma due to the
      systemic side effects associated with its use. No topical formulation of
      acetazolamide is available, mainly because of it having a limited aqueous
      solubility and poor corneal permeation. To enhance the bioavailability of
      acetazolamide by the topical route and to improve the corneal permeability of the
      drug, niosomes of acetazolamide were prepared (employing span 60 and cholesterol)
      by different methods. Transmission electron microscopy (TEM) of the selected
      formulation was carried out to study the morphology. Niosomes were also prepared
      in the presence of dicetyl phosphate and stearylamine to obtain negatively and
      positively charged vesicles, respectively. It was found that the reverse-phase
      evaporation method (REV) gave the maximum drug entrapment efficiency (43.75%) as
      compared with ether injection (39.62%) and film hydration (31.43%) techniques.
      Drug entrapment efficiency varied with the charge and the percent entrapment
      efficiency for the REV method was 43.75, 51.23 and 36.26% for neutral, positively
      charged and negatively charged niosomes, respectively. Corneal permeability
      studies, however, showed that the percent permeation and the apparent
      permeability coefficient for the charged niosomes were less than for the neutral
      ones. A bioadhesive niosomal formulation of acetazolamide was also prepared and
      compared with the positively charged formulation, considering that both of them
      would have a prolonged stay in the cul-de-sac because of their expected
      interactions with mucin. The formulations were also compared based on their
      intraocular pressure (IOP)-lowering capacity. The positively charged niosomes
      (REV2), although showing good corneal permeability and pharmacodynamics, were
      however found to be inappropriate in terms of the corneal cell toxicity. The
      bioadhesive coated formulation (REV1bio) compared well with REV2 and also showed
      a much lesser toxicity. Further, the IOP-lowering effect of the developed
      formulations was compared with that of a marketed formulation of dorzolamide 2%,
      a topical carbonic anhydrase inhibitor. The developed niosomal formulations of
      acetazolamide showed a comparable physiological effect (33% reduction of IOP in
      REV1bio and 37% reduction in dorzolamide) with a duration of up to 6 h (the
      duration being 3 h for dorzolamide). Results of the study indicate that it is
      possible to develop a safe (as indicated by corneal toxicity studies) and
      physiologically active topical niosomal formulation of acetazolamide relative in
      efficiency to the newer local carbonic anhydrase inhibitor, dorzolamide. The
      developed formulations can form a cost effective treatment plan, which is
      especially important in the treatment of glaucoma, a chronic ailment affecting
      middle-aged to old patients.

PMID- 15563758
TI  - Novel thiocyanato complexes with potent cytotoxic and antimicrobial properties.
AB  - The aim of the present study was to assess the cytotoxic and antimicrobial
      properties of seven new thiocyanato complexes: Ni(C(9)H(11)N(2)O)(SCN),
      Cu(C(9)H(11)N(2)O)(SCN), Pd(C(9)H(11)N(2)O)(SCN), Pt(C(9)H(11)N(2) O) (SCN),
      K[Ti(C(9)H(11)N(2)O)(SCN)(3)], Au(C(9)H(11)N(2)O)(SCN), and
      K[V(O)(C(9)H(11)N(2)O)(SCN)] (T(1)-T(7), respectively). All the complexes showed
      toxicity against brine shrimp nauplii (Artemia salina L.). The titanium-based
      complex, T(5), exhibited potent toxicity, with a lethal concentration 50% (the
      concentration of test compound that kills 50% of A. salina) value of 1.59 microg
      mL(-1). These new complexes also exhibited promising antibacterial and antifungal
      properties. A macrodilution technique was used to estimate the minimum inhibitory
      concentrations of the seven bioactive complexes. Minimum inhibitory
      concentrations were found to be 8-64 microg mL(-1) against the tested bacterial
      species.

PMID- 15563759
TI  - Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly
      soluble drugs.
AB  - The purpose of this work was to improve the oral bioavailability of poorly
      soluble drugs by incorporation into solid lipid nanoparticles (SLNs). All-trans
      retinoic acid (ATRA) was used as a poorly soluble model drug. Different
      formulations of SLNs loaded with ATRA were successfully prepared by a high
      pressure homogenization method and using Compritol 888 ATO as lipid matrix. The
      particle size and distribution, drug loading capacity, drug entrapment efficiency
      (EE %), zeta potential, and long-term physical stability of the SLNs were
      investigated in detail. Drug release from two sorts of ATRA-SLN was studied and
      compared with the diffusion from ATRA solution in 0.1 M HCl, distilled water and
      phosphate buffer (pH 7.40), using a dialysis bag method. A pharmacokinetic study
      was conducted in male rats after oral administration of 8 mg kg(-1) ATRA in
      different formulations and it was found that the relative bioavailability of ATRA
      in SLNs was significantly increased compared with that of an ATRA solution. The
      amount of surfactant also had a marked effect on the oral absorption of ATRA with
      SLN formulations. Although an emulsion formulation also increased ATRA
      absorption, it was too unstable for use in clinical situations. The absorption
      mechanism of the SLN formulations was discussed. These results indicate that ATRA
      absorption is enhanced significantly by employing SLN formulations. SLNs offer a
      new approach to improve the oral bioavailability of poorly soluble drugs.

PMID- 15563760
TI  - The effect of quercetin on the pharmacokinetics of verapamil and its major
      metabolite, norverapamil, in rabbits.
AB  - We have investigated the effect of quercetin on the pharmacokinetics of verapamil
      and its major metabolite, norverapamil, in rabbits. Pharmacokinetic parameters of
      verapamil and norverapamil were determined after the oral administration of
      verapamil (10 mg kg(-1)) to rabbits in the presence and absence of quercetin (5.0
      and 15 mg kg(-1)). While co-administration of quercetin concurrently was not
      effective to enhance the oral exposure of verapamil, pretreatment of quercetin 30
      min before verapamil administration significantly altered the pharmacokinetics of
      verapamil. Compared with the control group (given verapamil alone), the C(max)
      and AUC of verapamil increased approximately twofold in the rabbits pretreated
      with 15 mg kg(-1) quercetin. There was no significant change in T(max) and
      terminal plasma half-life (t(1/2)) of verapamil in the presence of quercetin.
      Consequently, absolute and relative bioavailability values of verapamil in the
      rabbits pretreated with quercetin were significantly higher (P < 0.05) than those
      from the control group. Metabolite-parent AUC ratio in the rabbits pretreated
      with quercetin decreased by twofold compared with the control group, implying
      that pretreatment of quercetin could be effective to inhibit the CYP3A4-mediated
      metabolism of verapamil. In conclusion, pretreatment of quercetin significantly
      enhanced the oral exposure of verapamil. This suggested that concomitant use of
      quercetin or a quercetin-containing dietary supplement with verapamil requires
      close monitoring for potential drug interaction.

PMID- 15563761
TI  - Pharmacokinetics of intravenous and oral DA-8159, a new erectogenic, in rats with
      protein-calorie malnutrition.
AB  - Influence of dietary protein deficiency on the pharmacokinetics of DA-8159 and
      one of its metabolites, DA-8164, was investigated after intravenous and oral
      administration of DA-8159 at a dose of 30 mg kg(-1) to male Sprague-Dawley rats
      allowed free access to a 23% (control) or 5% (protein-calorie malnutrition, PCM)
      casein diet for 4 weeks. The total area under the plasma concentration-time curve
      from time zero to time infinity (AUC) values of DA-8164 were significantly
      smaller after both intravenous (87.0 vs 162 microg min mL(-1)) and oral (144 vs
      319 microg min mL(-1)) administration of DA-8159 to PCM rats. This could be due
      to the decrease in CYP3A1/2 (50-60%) in the rats because DA-8164 was mainly
      formed via CYP3A1/2 in rats. This could be supported by significantly slower in
      vitro CL(int) (2.04+/-0.646 vs 3.15+/-0.693 microL min(-1) (mg protein)(-1)) for
      the formation of DA-8164 in hepatic microsomal fraction of PCM rats. After
      intravenous administration of DA-8159, the AUC values of DA-8159 were not
      significantly different between the two groups of rats although the AUC of DA
      8164 was significantly smaller in PCM rats, and this may be due to the minor
      metabolic pathway of DA-8164 in rats. However, after oral administration of DA
      8159, the AUC of DA-8159 was significantly greater in PCM rats (194 vs 122 microg
      min mL(-1)). This was not due to enhanced absorption of DA-8159 from the
      gastrointestinal tract in the rats but may be due to a decreased intestinal first
      pass effect of DA-8159 in the rats.

PMID- 15563762
TI  - Thermogenic effect of YM348, a novel 5-HT2C-receptor agonist, in rats.
AB  - We have investigated the effect of S-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1
      methylethylamine (YM348), a novel 5-HT(2C)-receptor agonist, on body temperature
      and energy expenditure in Wistar rats. m-Chlorophenylpiperazine (mCPP) and S-2-(6
      chloro-5-fluoroindol-1-yl)-1-methylethylamine (RO 60-0175) were used as reference
      5-HT(2C)-receptor agonists. Administration of YM348, mCPP and RO 60-0175 dose
      dependently and significantly increased body temperature in rats. YM348- or RO 60
      0175-induced hyperthermia was significantly attenuated by the non-selective 5
      HT(2)-receptor antagonist methysergide and the selective 5-HT(2C)-receptor
      antagonist SB242084, but not by the selective 5-HT(2A)-receptor antagonist
      MDL100907. mCPP-induced hyperthermia was significantly attenuated by
      methysergide, SB242084 and MDL100907. In addition to the increase in body
      temperature, YM348, mCPP and RO 60-0175 produced dose-related and significant
      increases in energy expenditure. YM348-, mCPP- and RO 60-0175-induced increases
      in energy expenditure were significantly attenuated by methysergide and SB242084
      but not by MDL100907. These results suggested that 5-HT(2C)-receptor stimulation
      increased body temperature and energy expenditure and that the 5-HT(2C)-receptor
      was the target receptor in the thermogenic effect of YM348 in Wistar rats.

PMID- 15563763
TI  - The antioxidative effect of icariin in human erythrocytes against free-radical
      induced haemolysis.
AB  - Icariin (2-(4'-methoxyl phenyl)-3-rhamnosido-5-hydroxyl-7-glucosido-8-(3'-methyl
      2-butylenyl)-4-chromanone) is the major component in Herba Epimedii used in
      traditional Chinese medicine for the treatment of atherosclerosis. This work
      focuses on the antioxidative effect of icariin on free-radical-induced haemolysis
      of human erythrocytes, in which the initial free radical derives from the
      decomposition of 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) at
      physiological temperature. To reveal the structure-activity relationship of
      icariin, the antioxidant effects of two structural analogues of icariin, acacetin
      (2-(4'-methoxylphenyl)-5,7-dihydroxylchromone) and norwogonin (2-phenyl-5,7,8
      trihydroxylchromone), on the same experimental system were examined as well. It
      was found that all these chromone derivatives (Chm-OHs) dose-dependently
      protected human erythrocytes against free-radical-induced haemolysis. The order
      of antioxidative activity was norwogonin > acacetin > icariin by the analysis of
      the relationship between the concentration of Chm-OHs and the prolongation
      percentage of the lag time of haemolysis (PP%). It was also proved that the
      phenyl hydroxyl group attached to the chromone ring at 7-position cannot trap the
      free radical. On the contrary, phenyl hydroxyl groups at the 5- and 8-position in
      norwogonin made it a significant antioxidant in AAPH-induced haemolysis. The more
      hydroxyl groups attached to the chromone ring, the higher the antioxidative
      activity in protecting erythrocytes against free-radical-induced peroxidation.

PMID- 15563764
TI  - Receptor regulatory properties evident in the molecular similarity of serotonin
      receptor ligands and purine nucleotides.
AB  - Previous computational studies have explored the relative molecular similarity
      inherent in the ligands of neurotransmitter-regulated cell receptors and purine
      nucleotides. This study presents the results of an investigation of the major
      serotonin (5-HT) receptor classes, using molecular superimposition and fitting
      data. Ligands for 5HT(1B/C/D) and 5HT(4/7) receptors identified pharmacophores in
      the adenine ring of ATP. 5-HT(2) and 5-HT(3) receptor ligands identified
      pharmacophores in the guanosine nucleotide and cyclic nucleotide, respectively.
      The described molecular similarity is consistent with the cyclic nucleotide
      responses observed during signal transduction events initiated by 5-HT, and the
      reported similarity between ligands of the 5-HT(1B) and 5-HT(1D), 5-HT(1A) and 5
      HT(7), and 5-HT(4) and 5-HT(3) receptors. The results are discussed in terms of
      current pharmacophoric models and signal transduction events involving
      interaction between G-protein receptors and catalytic sites.

PMID- 15563765
TI  - Enhancement of natural killer cell activity of aged mice by modified arabinoxylan
      rice bran (MGN-3/Biobran).
AB  - The present study is aimed to examine the possibility of enhancement of natural
      killer (NK) cell activity in aged C57BL/6 and C3H mice using MGN-3, a modified
      arabinoxylan from rice bran. Intraperitoneal injection of MGN-3 (10 mg kg(-1) per
      day) caused a remarkable increase in the peritoneal NK activity as early as 2
      days (35.2 lytic units), and the level remained elevated through day 14. The
      control aged mice had a level of 5.8 lytic units. Enhancement in NK activity was
      associated with an increase in both the binding capacity of NK cells to tumour
      targets and in the granular content as measured by BLT-esterase activity.
      Treatment did not alter the percentage of peritoneal NK cells. Data showed that
      peritoneal macrophages inhibit NK activity. In conclusion, MGN-3 enhances murine
      NK activity of aged mice and may be useful for enhancing NK function in aged
      humans.

PMID- 15563766
TI  - Effects of oral administration of extracts of Hypericum perforatum (St John's
      wort) on brain serotonin transporter, serotonin uptake and behaviour in mice.
AB  - The pharmacological effects of extracts of Hypericum perforatum (St John's wort)
      were characterized in-vitro and ex-vivo, in relation to its behavioural effects.
      In in-vitro experiments, St John's wort inhibited brain synaptosomal
      [(3)H]serotonin uptake in mice with little effect on specific [(3)H]paroxetine
      binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for
      [(3)H]serotonin uptake (molar concentration of unlabelled drug necessary to
      displace 50% of specific uptake) correlated well with the inhibition constant
      K(i) value for [(3)H]paroxetine binding in mouse brain. Oral administration of St
      John's wort (900 mg kg(-1)), paroxetine (1 mg kg(-1)) and sertraline (10 mg kg(
      1)) brought about significant increases in the K(m) value for [(3)H]serotonin
      uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific
      [(3)H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly
      inhibited marble-burying behaviour in mice and the time-course of attenuation of
      this behaviour by St John's wort was similar to that of [(3)H]serotonin uptake
      inhibition. In the forced swimming test, St John's wort, but not SSRIs,
      suppressed the immobility time of mice after oral administration. These results
      provide the first in-vivo evidence to suggest that the mode of antidepressant
      action of St John's wort differs from that of SSRIs. Thus, this study may have a
      significant impact on phytotherapy with St John's wort.

PMID- 15563767
TI  - Does the well-stirred model assess the intestinal first-pass effect well?
AB  - The pre-systemic intestinal extraction ratio (E(g)) has been estimated by an
      equation based on the well-stirred model, which does not have a term of membrane
      transport. In this report, we have identified the application limitations of the
      well-stirred model equation to assess the pre-systemic intestinal extraction
      ratio. The E(g) of metoprolol (CYP2D6 substrate) was assessed by three methods.
      Intrinsic clearances for metoprolol metabolism in hepatic and gastrointestinal
      microsomes were from a published report. Method 1 (model-independent method): the
      E(g) of 0.228 was obtained according to the equation, F = F(f) x (1 - E(g)) x
      F(h), where F, F(f) and F(h) were the bioavailability, the fraction entering the
      intestinal tissue and the hepatic availability, respectively. Method 2: the E(g)
      of 0.0071 was calculated according to the well-stirred model equation, and was
      much lower than the value of 0.228. Method 3: the E(g) of 0.213 was obtained by
      the transport-metabolism-flow (TMF) model equation, and was much closer to the
      value of 0.228 obtained by the model-independent method than the E(g) of 0.0071
      calculated by the well-stirred model equation. Therefore, we propose that the
      factor of membrane transport process be incorporated into the pharmacokinetic
      model for the assessment of the pre-systemic intestinal extraction ratio.

PMID- 15563768
TI  - Carbonyl reduction of naltrexone and dolasetron by oxidoreductases isolated from
      human liver cytosol.
AB  - The opioid receptor antagonist naltrexone and the antiemetic 5-HT(3) receptor
      antagonist dolasetron are ketonic drugs that are efficiently reduced to their
      corresponding alcohols in-vivo. These experiments aimed at characterizing the
      role in these reactions of individual oxidoreductases present in human liver
      cytosol. Aldo-keto reductases (AKRs) and carbonyl reductase (CR, EC 1.1.1.184)
      purified from human liver cytosol were incubated with varying substrate
      concentrations and 6beta-naltrexol or reduced dolasetron were analysed by HPLC.
      AKR1C1, AKR1C2, and AKR1C4 were able to reduce both substrates. On the basis of
      k(cat)/K(m) values, AKR1C4 was nearly 1000-fold more efficient in reducing
      naltrexone than was AKR1C1, while AKR1C2 was of intermediate efficiency.
      Substrate inhibition was observed on incubating AKR1C2 or AKR1C4 with naltrexone.
      In contrast, dolasetron was also a substrate of CR. AKR1C1 and AKR1C4 were the
      most efficient enzymes in producing reduced dolasetron. We concluded that the
      efficient reduction of naltrexone by AKR1C4 probably causes the high 6beta
      naltrexol/naltrexone ratio in man. The rapid disappearance from human plasma of
      dolasetron given intravenously and its virtual absence after oral dosage are
      explained by its liability to reduction by several enzymes, including CR which
      shows widespread expression in human tissues.

PMID- 15563769
TI  - Natural phenylpropanoids inhibit lipoprotein-induced endothelin-1 secretion by
      endothelial cells.
AB  - There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL)
      might be involved in the pathogenesis of atherosclerosis and it has been reported
      that polyphenols inhibit LDL peroxidation and atherosclerosis. Endothelin-1 (ET
      1) is a potent vasoconstrictor peptide isolated from endothelial cells and it
      induces smooth muscle cell proliferation. ET-1 secretion is increased in atheroma
      and induces deleterious effects such as vasospasm and atherosclerosis. The goal
      of this study was to test the effect of four natural phenolic compounds against
      copper-oxidized LDL (Cu-LDL)-induced ET-1 liberation by bovine aortic endothelial
      cells (BAEC). The tested compounds were phenylpropanoid glycosides previously
      isolated from the aerial parts of Marrubium vulgare L. (acteoside 1, forsythoside
      B 2, arenarioside 3 and ballotetroside 4). ET-1 secretion increased when cells
      were incubated with Cu-LDL but the compounds 1-4 inhibited this increase. These
      results were confirmed by quantitative-polymerase chain reaction (QPCR) analysis.
      Since ET-1 plays an important role in atherosclerosis development, our work
      suggests that the tested phenylpropanoids could have a beneficial effect in
      inhibiting atherosclerosis development.

PMID- 15563770
TI  - The vagaries of prostate cancer screening.

PMID- 15563771
TI  - Will men attribute fault to their GP for adverse effects arising from
      controversial screening tests? An Australian study using scenarios about PSA
      screening.
AB  - OBJECTIVE: To determine men's attribution of fault for adverse consequences of
      prostate-specific antigen (PSA) screening. SETTING: Representative, population
      based sample recruited from Sydney, Australia (n=405). METHODS: Telephone
      interview to assess reactions to two scenarios: Scenario 1, depicting a GP who
      dismisses an opportunity to order a PSA test (missed diagnosis); and Scenario 2,
      depicting a GP who recommends PSA screening to a patient who then experiences
      adverse outcomes from treatment of his prostate cancer (iatrogenic consequences).
      RESULTS: Two-thirds of participants (66.9%) ascribed fault to the GP in Scenario
      1. Men in fair or poor health (adjusted odds ratio [AOR] 1.81; 95% confidence
      interval [CI] 1.04-3.12; p=0.03) and those with better knowledge about PSA
      screening (AOR 0.98; 95% CI 0.97-0.99; p=0.002) were significantly and
      independently more likely to ascribe fault in Scenario 1. By contrast, only 15.8%
      of participants ascribed responsibility to the GP in Scenario 2. Older men (AOR
      1.05; 95% CI 1.00-1.10; p=0.04) and those with higher levels of decisional
      conflict (AOR 1.19; 95% CI 1.04-1.37; p=0.01) were significantly and
      independently more likely to ascribe responsibility. CONCLUSION: Public education
      could better target men's tendency to ascribe fault to GPs when they miss an
      opportunity to diagnose prostate cancer early through PSA screening, even though
      the corollary of potential iatrogenic consequences is perceived as less
      blameworthy. As decisional conflict and knowledge were found to predict
      attribution of fault, evidence-based information may reduce the medicolegal
      volatility of this controversy.

PMID- 15563772
TI  - The reference range and within-person variability of thyroid stimulating hormone
      during the first and second trimesters of pregnancy.
AB  - OBJECTIVE: To further explore first and second trimester reference ranges for
      thyroid stimulating hormone (TSH) and examine within-person variability of TSH
      and thyroid peroxidase (TPO) antibody. SETTING: Women coming for routine prenatal
      care in early pregnancy agreed to participate in a trial of integrated serum
      screening for Down's syndrome. Two serum samples were obtained from each woman,
      one each in the first and second trimesters. These samples were also available
      for TSH and TPO measurements in the present study. METHODS: TSH and TPO antibody
      measurements were performed in 1126 women with ultrasound-dated pregnancies who
      provided serum samples in both trimesters. TSH reference ranges were established
      for the entire cohort and for the antibody-negative subgroup. Within-person
      variability of TSH measurements between trimesters was examined. RESULTS: Median
      TSH values are lower in the first trimester than in the second (1.00 versus 1.29
      mIU/l), but 98th centile values are higher (5.20 versus 4.18 mIU/l). High
      correlation exists between individual women's first and second trimester TSH
      measurements (r=0.75, r2=0.56, p<0.001). Among 23 women with TSH values above the
      98th centile in the second trimester, 17 (74%) were over the 95th centile in the
      first trimester. TPO antibody measurements are also highly correlated between
      trimesters (r=0.97, r)=0.94). CONCLUSION: Proper interpretation of TSH
      measurements during pregnancy requires that laboratories establish and monitor
      appropriate reference ranges. TSH levels show high within-person consistency
      between trimesters.

PMID- 15563773
TI  - Identifying homozygous sickle cell disease when neonatal screening is not
      available: a clinic-based observational study.
AB  - OBJECTIVES: Life-threatening clinical complications can occur in the first years
      of life in people with homozygous sickle cell disease. There is consensus that a
      clinical care programme comanaged by a specialist clinic should follow early-life
      disease identification. In a setting without widespread neonatal screening for
      this disease, we predict the percentage of affected births that enrol in
      specialist clinics during childhood, and the percentage that enrol early enough
      to benefit from penicillin prophylaxis (which is offered until five years of
      age). SETTING: A retrospective study of enrolment between 1973 and 1999 at three
      clinics in Jamaica, the country's only referral centres for sickle cell disease.
      RESULTS: Among enrolees not screened at birth, observed enrolment by age five was
      10.1% (95% confidence interval [CI] 5.7-16.7%) among 1974 births, which is
      predicted to rise to 35.7% (95% CI 35.0-36.4%) among 1999 births. Observed
      enrolment by 18 years of age was 45.9% (95% CI 35.7-58.2%) among 1974 births,
      which is predicted to peak at 61.9% (95% CI 60.5-63.2%) among 1984 births, and
      fall to 48.9% (95% CI 40.9-56.9%) among 1999 births. Median age at enrolment was
      10.5 years (95% CI 10.0-11.3). CONCLUSIONS: Based on 1999 estimates, almost 65%
      of children affected by homozygous sickle cell disease not identified at birth
      will not benefit from important early-life clinical intervention, and half will
      not enrol for specialised care by their 18th birthday. Among patients that enrol,
      half do so in adolescence when management is less focused on preventive care.

PMID- 15563774
TI  - A case-control study to estimate the impact on breast cancer death of the breast
      screening programme in Wales.
AB  - OBJECTIVES: The aim of this study was to estimate the effect of service
      screening, as provided by the NHS breast screening programme, on breast cancer
      mortality in Wales. Furthermore, we wished to ascertain whether a reduction in
      breast cancer mortality consistent with that observed in the randomised screening
      trials was being achieved. SETTING: The NHS Breast Screening Programme in Wales,
      managed by Breast Test Wales, with headquarters in Cardiff. METHODS: A case
      control study design with 1:2 matching. The cases were deaths from breast cancer
      in women aged 50-75 years at diagnosis who were diagnosed after the instigation
      of screening in 1991 and who died after 1998. The controls were women who had not
      died of breast cancer or any other condition during the study period. One was
      from the same GP practice and the other from a different GP practice within the
      same district, matched by year of birth. RESULTS: Based on 419 cases, the odds
      ratio for risk of death from breast cancer for women who have attended at least
      one routine screen compared to those never screened was 0.62 (95% confidence
      interval [CI] 0.47-0.82, p=0.001). After excluding cases diagnosed prior to 1995
      and adjusting for self-selection bias, the estimated mortality reduction was 25%
      (odds ratio=0.75, 95% CI 0.49-1.14, p=0.09). CONCLUSION: The Breast Test Wales
      screening programme is achieving a reduction in breast cancer mortality of 25% in
      women attending for screening, which is consistent with the results of the
      randomized controlled trials of mammographic screening.

PMID- 15563775
TI  - Age-specific interval breast cancers in New South Wales and meta-analysis of
      studies of women aged 40-49 years.
AB  - OBJECTIVE: To compare interval cancers in the 40-49 year age group with other age
      groups in New South Wales and with published trials and service studies. SETTING:
      New South Wales data were derived from the population-based biennial mammography
      screening program, which achieved state-wide coverage in 1995. Women aged 40-49
      years screened during 1995-1998 were included. METHODS: Bilateral two-view
      mammography with reading by two radiologists was employed for biennial screening
      examinations. Interval cancers were detected by the screening program and by
      linkage with the state-wide cancer registry. Incidence of interval cancer based
      on the date of diagnosis was estimated as a proportion of the expected underlying
      breast cancer incidence for first- and second-year interval cancers. Sensitivity
      estimates were also calculated. Comparative data for the 40-49 year age group
      were derived from the published literature for meta-analyses of trial and service
      studies. RESULTS: Interval cancer rates for New South Wales decreased with
      increasing age, with the highest proportional incidence in the 40-49 year age
      group for first year (56%, 95% confidence interval [CI] 50-62%) and second-year
      (86%, 95% CI 82-90%) interval cancers. Proportional incidence for women aged 50
      69 years for first- and second-year interval cancers was 31% (95%CI 29-33%) and
      50% (95% CI 47-52%) respectively. Sensitivity estimates for the program increased
      significantly with age, with lowest sensitivity estimates evident for women 40-49
      years. In women aged 40-49 years the meta-analysed proportional incidence rate
      for randomised trials of screening for first- and second-year interval cancers
      was 42% (95% CI 21-62%) and 63% (95% CI 55-71%) respectively, while for service
      studies it was 44% (95% CI 31-58%) and 72% (95% CI 51-92%). Proportional
      incidence in the New South Wales program for women aged 40-49 years was not
      significantly different to the meta-analysed proportional incidences for trial
      and service studies in the first year, or for service studies in the second year.
      CONCLUSION: Proportional incidence of interval cancer was significantly higher in
      women aged 40-49 years in New South Wales relative to older age groups, but did
      not differ significantly from service studies of women in a similar age group.
      The effectiveness of mammography screening for this age group needs to be
      examined in view of the comparatively high rate of interval cancers.

PMID- 15563776
TI  - Application of symptom checklist for screening major depression by annual health
      examinations: a cross-validity study in the workplace.
AB  - To evaluate the effectiveness of a symptom checklist to detect major depression,
      1424 subjects completed a pre-existing 22-item general symptom checklist at
      periodic health examinations. All subjects were interviewed to enable
      confirmatory diagnosis of major depression. Nine out of the 22 symptoms were more
      frequently reported in the subjects with major depression than in those without
      such a disorder. The results were confirmed in 434 new subjects receiving the
      same intervention the following year. The results of this study suggest the
      effectiveness of symptom checklists as tools to detect subjects with depression.
      Among them, the nine-item checklist has an advantage in practical use for its
      simplicity.

PMID- 15563777
TI  - Valuing cost in cost utility analysis of screening programme.

PMID- 15563780
TI  - [Clinical practice guidelines for prevention of colorectal cancer: towards an
      integral, integrated and coordinated approach].

PMID- 15563781
TI  - [Current situation in prenatal diagnosis].

PMID- 15563782
TI  - [Changes in tobacco use in the general population of Barcelona, 1983-2000].
AB  - OBJECTIVES: To analyze the prevalence trends for smoking and its determinants in
      the general population of Barcelona from 1983 to 2000. DESIGN: Time series study.
      SETTING: Health survey based on home interviews of a representative sample of the
      general population of Barcelona. PARTICIPANTS: In the years 1983, 1992, and 2000
      we interviewed 3134, 5004, and 10,000 persons, respectively. MAIN OUTCOME
      MEASURES AND RESULTS: Between 1983 and 2000 daily tobacco use showed a steady
      tendency to decrease among men, with a prevalence that decreased from 54.6% to
      38.3%, while in women, smoking increased between 1983 and 1992 (from 20.9% to
      25.4%) but remained stable in 2000 (24.5%). The proportion of smokers who said
      they wanted to quit increased in both sexes from 1992 (54.2%) to 2000 (65.7%).
      During this period the proportion of smokers who said their doctor had advised
      them to quit increased from 36.1% to 48.1%. The trends for both sexes showed that
      consumption of tobacco products was greater among less privileged socioeconomic
      groups. CONCLUSIONS: The results of this study confirm the decrease in the
      prevalence of daily consumption of tobacco products and the increase in smokers
      who would like to quit, in parallel with the increase in advice from physicians
      to quit. However, the trends among younger groups remained stable, a finding that
      makes it necessary to intensify efforts aimed at this population group.

PMID- 15563783
TI  - [Trends in tobacco use in Spain].

PMID- 15563784
TI  - [Evolution of tobacco habits during pregnancy and postpartum period].
AB  - OBJECTIVE: To describe how smoking evolved during pregnancy and a long postpartum
      period, with analysis of the factors associated with giving up tobacco. DESIGN:
      Retrospective, descriptive study. SETTING: Badia del Valles Primary Care Centre
      (Barcelona). PARTICIPANTS: Women with pregnancies coming to term over a 3-year
      period (n=309, 68% of the target population). MAIN MEASUREMENTS: Tobacco
      dependency before pregnancy. Giving up during pregnancy and related factors
      (social and personal, nature of tobacco habit, health beliefs). Backsliding after
      birth. RESULTS: 50% smoked before pregnancy. 46% of these gave up smoking during
      pregnancy and 44% cut down. In primigravidae, there was greater risk of their
      continuing to smoke, the greater their previous tobacco consumption was (OR=5.3
      if > or =20 cigarettes a day and OR=4.7 for 10-19 cigarettes a day) or if they
      did not believe in the effect of tobacco on the baby's health (OR=3.9). In women
      pregnant for the second time or more, it was associated with not giving up
      tobacco in previous pregnancies (OR=43.8) and with their partner's tobacco habit
      (OR=7.2). In the 2 years after birth 80% of those who gave up relapsed.
      CONCLUSIONS: In our milieu a high prevalence of smokers before pregnancy coexists
      with a high rate of giving up during pregnancy. In all, 1 in every 4 women smokes
      during pregnancy. Giving up tobacco was related to factors such as dependency,
      motivation, environment and prior experience.

PMID- 15563785
TI  - [Health care expenditure in Spain compared with developed Europe, 1985-2001. The
      Spanish primary health care, the European Cinderella].
AB  - OBJECTIVE: To describe the evolution of the funds distribution in our health care
      system since the start of the primary care reform to 2001, in comparison with the
      European countries members of the Organisation for Economic Co-operation and
      Development (OECD). DESIGN: A longitudinal descriptive and retrospective study.
      PARTICIPANTS: European countries members of the OECD. SETTING: Countries members
      of the OECD. METHODS: The data come from the OECD database Health Data 2003. The
      data refer to period 1985-2001, and to a group of variables of health care
      expenditure by sectors and of income (Gross Domestic Product [GDP] per capita).
      We compare Spanish data series with those of the group of 22 European members
      countries of the OECD. RESULTS: Europe increased public expenditure on out
      patient care both as a percentage of public health care expenditure and as a
      percentage of GDP. Spain reduced public expenditure on out-patient care in both
      senses. Spanish public expenditure on in-patient care reduced a great part of its
      difference with Europe so that since 1995 it is found, as a percentage of GDP, in
      the European average and, as per capita, it is according with the Spanish income.
      In contrast, public expenditure on out-patient care as a percentage of GDP in
      Spain is very much lower than the European average and, as per capita, is very
      much lower than the Spanish income. The Spanish private expenditure on out
      patient is found among the highest in Europe and, compared with Europe, exceeds
      very much Spanish income, in contrast with his homonymous public. The Spanish
      private expenditure on in-patient care is found among the lowest in Europe and,
      compared with Europe, is very much lower than Spanish income level. CONCLUSIONS:
      With respect to public resources assigned, the reform of primary care in Spain
      has not been useful to approach Spanish primary health care level to Europe, in
      contrast with the Spanish hospital level. The difference between Spain and Europe
      in public expenditure on out-patient care as a percentage of GDP is, even, bigger
      than the one there was when the reform of Spanish primary care started.

PMID- 15563786
TI  - [It was all Hippocrates' fault].

PMID- 15563787
TI  - [Spanish adaptation of the European guidelines on cardiovascular prevention (and
      II)].

PMID- 15563788
TI  - [Schizophrenia in primary health care centers: the SASPE study (alert signs and
      prodromic symptoms of schizophrenia in primary health care)].
AB  - OBJECTIVES: To contribute to the knowledge of the alert signs and precursors of
      the schizophrenia, just as they can appear in the childhood, and of the prodromic
      signs other ages. DESIGN: Five descriptive studies: three retrospective, one
      transversal and one longitudinal study, based in the revision of clinical
      histories of an Community Mental Health Unit closely linked with the APS,
      additional revisions of the clinical histories of Family Doctors and Peadiatrics
      of Primary Care, and structured interviews with patients, patient's offspring,
      and PHC professionals. Two prospective studies: one, with schizophrenic's
      children; other, of children with alert signs detected in the first childhood.
      LOCATION OF THE PROJECT: USM-MHU of Sant Marti-La Mina, 5 Sanitary Basic Areas of
      Barcelona and Sant Adria (Barcelona), besides the Functional Unit of Attention to
      the First Childhood of Sant Marti (Barcelona). PARTICIPANTS: Schizophrenic
      patients and relatives detected by the USM-MHU. Schizophrenic patients and
      relatives not detected by the USM. MHU-USM assistance staff and assistance staff
      of 5 ABS and of the Functional Unit of Attention to the First Childhood (UFAPI).
      Children with alert signs detected in the UFAPI and children with alert signs or
      risk factors detected in the EAP and in the Pediatric Teams of PC. METHODOLOGY
      AND INSTRUMENTS: Diagnoses DSM-IV. Structured interviews SCAN and IRAOS. Scales
      of positive and negative symptoms. Scales or screenings for the first childhood:
      ARBB, CBCL, and LISMEP. Structured interviews to determine precursory and
      prodromic signs: FETZ (Colony), ERIE-IRAOS (Hamburg-Barcelona), ERIE-red (reduced
      version of the IRAOS, adapted by the investigating team).

PMID- 15563789
TI  - [Indication of a contraceptive method to a teenager: subcutaneous implant of
      gestagen].

PMID- 15563790
TI  - [Dependency evaluation and geriatric health].

PMID- 15563791
TI  - [Depression and anxiety in irregular immigrants].

PMID- 15563792
TI  - [Television: an enemy at home].

PMID- 15563794
TI  - [Monitoring of antithrombin levels in women on oral contraceptive treatment].

PMID- 15563796
TI  - [Subcutaneous administration of vitamin B12].

PMID- 15563797
TI  - [Differential circadian rhythms in myocardial infarction according to its extent
      by electrocardiogram].
AB  - BACKGROUND AND OBJECTIVE: To determine the existence of circadian rhythm in the
      time of onset of acute myocardial infarction (AMI) according to their extension
      type (Q-wave vs. non-Q-wave). PATIENTS AND METHOD: We studied a retrospective
      cohort of patients from a multicentre study of myocardial infarction (ARIAM study
      group). We collected information about 54,249 infarctions from the data base of
      the ARIAM (Analysis of Delay in AMI) Spanish multicentre study. The following
      variables were analysed: general variables --age, gender, previous ischemic heart
      disease, outcome at coronary care unit, infarction electrocardiograph type (Q
      wave or non-Q wave) and location of AMI--, cardiovascular risk factors, and
      previous drug treatment of the patients. To verify the presence of circadian
      rhythm we developed a simple test of equality of time series based on the
      multiple-sinusoid cosinor analysis. Three sinusoids (24-12-8 h periods) were
      used. RESULTS: The time of pain onset shows circadian rhythm (p < 0.0000), which
      also is observed in both infarction electrocardiograph characteristics subgroups
      (Q-wave infarction and non-Q-wave infarction) (p < 0.0000). Q-wave infarction
      shows sinusoid curve with one maximum morning peak and non-Q-wave shows bimodal
      curve, with two peaks. Comparison between their curves shows statistical
      significance (p < 0.0000). CONCLUSIONS: AMI onset follows a circadian rhythm
      pattern, which is also observed in analysed subgroups. Differences in the
      circadian rhythm according to the Q/non-Q wave infarction characteristics, could
      be determined by different physiopathologic mechanism. The cosinor model fit with
      three components (24, 12 and 8-hour-periods) show good sensitivity to determine
      circadian rhythm.

PMID- 15563798
TI  - [Prevalence and risk factors of varicose veins in adults].
AB  - BACKGROUND AND OBJECTIVE: We intended to estimate the prevalence of varicose
      veins in the mature population of the Valencia Community and to analyze its
      relationship with socio-demographic variables, self-reported health status, body
      mass index and the presence of hemorrhoids, tobacco smoking, alcohol consumption
      and physical activity. SUBJECTS AND METHOD: Information on self-reported varicose
      veins was collected from 1,778 adults older than 14 years (819 men and 959 women)
      who participated in the Health and Nutrition Survey of the Valencia Community
      (Spain). We estimated the prevalence of varicose veins by age groups and sex. To
      explore the association between varicose veins and variables, we estimated
      adjusted odds ratios (OR) with 95% confidence intervals (CI 95%) by multiple
      logistic regression. RESULTS: The overall prevalence of varicose veins was 16.4%,
      with a much higher prevalence in women that in men (26.7% versus 5.5%) and with
      older age. Gender and age were the 2 strongest predictors of varicose veins in
      multivariate analysis. Women had seven times more risk than men (OR = 7.01; CI
      95%, 4.52-10.87) and those older than 35 years almost tripled the risk with
      respect to those aged 15-24 years. A body mass index of 30 kg/m2, a poor self
      reported health status and hemorrhoids were significantly associated with the
      presence of varicose veins. Employers showed higher risk than workers. A moderate
      alcohol consumption (< or = 1 drink/day) was associated with a protective effect
      (OR = 0.50; CI 95%, 0.28-0.88). Tobacco smoking and physical activity were not
      associated with varicose veins. CONCLUSIONS: Although being a woman and having an
      advanced age were the strongest predictors of varicose veins, other factors such
      as a high BMI, poor health status, hemorrhoids and some professional categories
      may be also important factors in their presentation. A moderate alcohol
      consumption seems to have a protective effect.

PMID- 15563799
TI  - [Continuous and momentous tobacco abstinence with pharmacologic therapy in
      clinical practice].
AB  - BACKGROUND AND OBJECTIVE: The objective of the study was to evaluate the
      effectiveness of the pharmacological treatment of tobacco dependence according to
      the criteria established by SEPAR. PATIENTS AND METHOD: Longitudinal, prospective
      and multicentre study. We included smokers aged more than 18 years who attended 5
      smokers clinics and received nicotine replacement therapy (NRT), bupropion or
      both. The punctual and continuous abstinence was studied at the 15, 30, 60, 90
      and 180 days with each one of the proposed treatments. Effective results were
      defined as the intention to treat. RESULTS: There were 904 smokers, 476 males and
      428 females, mean age 42.51 (10.09). Of the 904 individuals who started the
      treatment, 820, 776, 687, 719 and 679 were present at the follow-up sessions at
      15, 30, 60, 90 and 180 days, respectively. The punctual global abstinence at 15
      and 180 days was 65.6% and 43.1%, while the continuous one was 57.4% and 38.8% at
      two and six months, respectively. Significant differences were not observed with
      regard to the punctual or continuous abstinence among patients treated with NRT,
      bupropion or both. CONCLUSIONS: The pharmacological treatment of tobacco
      dependence used individually according to the recommendations of the clinical
      guidelines allows to obtain good results with regard to the momentous and
      continuous abstinence. The effectiveness of the different first line treatments
      is similar in all the phases of the therapeutic process.

PMID- 15563800
TI  - [Treatment of severe refractory psoriasis with infliximab].
AB  - BACKGROUND AND OBJECTIVE: Infliximab is a chimeric monoclonal antibody that binds
      to tumor necrosis factor alpha and blocks the inflammatory response. The purpose
      of this study was to assess the effects of infliximab in patients with severe and
      refractory psoriasis. PATIENTS AND METHOD: Eleven patients with severe and
      refractory psoriasis were included in an open-label clinical trial. Patients
      received infliximab 5 mg/kg intravenously at weeks 0, 2, 6 and every 8 weeks.
      Psoriasis Assessment and Severity Index (PASI) and BSA (Body Surface Assessment)
      were used to monitor disease activity with each dose. Results at weeks 6 and 30
      are shown. RESULTS: 90% of patients improved their PASI and BSA basal scores
      early at sixth week, achieving 63.6% (PASI75) and 72.7% (BSA50). This improvement
      was maintained until the 30th week (54.5% and 72.7%, respectively). Infliximab
      was well tolerated and there was no significant adverse reaction. CONCLUSIONS:
      Infliximab seems an effective therapy for severe and refractory psoriasis.

PMID- 15563801
TI  - [New horizons in the treatment of psoriasis].

PMID- 15563802
TI  - [SARS: solution by actions and responses with sense].

PMID- 15563803
TI  - [Speaking at medical meetings: how to succeed].

PMID- 15563804
TI  - [A 23 year-old man with cardiac tamponade].

PMID- 15563805
TI  - [Hepatic fascioliasis: thoughts about its diagnosis and complications].

PMID- 15563806
TI  - [Complementary and alternative medicine in patients with lymphoid neoplasms].

PMID- 15563807
TI  - [Anemia and heart failure].

PMID- 15563808
TI  - [Venous thrombosis and strain].

PMID- 15563809
TI  - [New proposals for improving the publication of clinical trials].

PMID- 15563810
TI  - [IgA-mediated autoimmune hemolytic anemia].

PMID- 15563811
TI  - [Pramipexole for intractable hiccups].

PMID- 15563812
TI  - [Cytomegalovirus myopericarditis in immunocompetent patients: two cases].

PMID- 15563814
TI  - [Cardiovascular risk of SCORE compared to Framingham. Consequences of the change
      proposed by the European Societies].
AB  - BACKGROUND AND OBJECTIVE: The European Societies in their last update introduce
      substantial changes to calculate the cardiovascular risk without thinking about
      the practical consequences. The objective was to evaluate the agreement between
      the charts of cardiovascular risk of second and the third recommendations of the
      European Societies to classify the patients of high risk and to analyze its
      differences. PATIENTS AND METHOD: Patients (1,227) belonging to 3 primary care
      centres. Risk calculated to the 10 years by means of the equation of Framingham
      and SCORE for countries lowers risk. A risk of Framingham > or = 20% or SCORE >
      or = 5% defined the high risk. RESULTS: The patients of high risk were 8.4%
      according to Framingham and 5.5% according to SCORE and the coefficient Kappa
      0.718. 41.7% of the patients of high risk disagreed: high risk Framingham and
      SCORE not (40 patients, 88.9%) and high SCORE and Framingham not (5 patients,
      11.1%). The group high risk Framingham and SCORE not 1 is constituted by 95% of
      males, age 60 years, cholesterol 246.2 mg/dl and 37.5% smokers. CONCLUSIONS: The
      chart SCORE and Framingham have an acceptable agreement, but classify from high
      risk different percentage of population and with different characteristics. The
      use of the chart of the SCORE would exclude an important group of patients with
      Framingham high risk.

PMID- 15563815
TI  - [Tables of coronary risk evaluation adapted to the Spanish population: the DORICA
      study].
AB  - BACKGROUND AND OBJECTIVE: Independent risk factors (smoking, hypertension,
      hypercholesterolemia and diabetes mellitus) are direct causes of coronary heart
      disease and are common in the population. Considering all independent factors
      together seems to be more appropriate to estimate the global risk of coronary
      heart disease. The objective of this paper was to estimate the global risk of
      coronary heart disease based on the Framingham function, adapted to the
      prevalence of risk factors in Spain. SUBJECTS AND METHOD: The prevalence of risk
      factors in the Spanish population was estimated based on pooled analysis of
      regional cross-sectional random population surveys. Prevalence estimates and
      incidence rate of coronary events were replaced in the Framingham equation
      accordingly. Risk probability for 10 years was estimated and risk tables were
      designed using a gradual color coding system according to an increasing risk.
      RESULTS: The estimated attributable fraction (AF) for hypertension in the Spanish
      population was 26.7% for men and 22.9% women; that for hypercholesterolemia was
      15.7% and 12.7% for men and women, respectively. Smoking was identified in the
      third position of the ranking order for males (AF 13.13%) and fourth for the
      female group (AF 3.71%). The prevalence of obesity was 13.2% for men and 17.5%
      for women. AF for obesity among men was 4% and it was 5% for women. CONCLUSIONS:
      An adaptation of the Framingham equation according to the prevalence of
      independent risk factors and incidence of coronary events in the Spanish
      population is useful to build instruments to estimate the 10-year global risk of
      coronary heart disease while a specific function based on a well-designed cohort
      study in not available in Spain.

PMID- 15563816
TI  - [Therapeutic compliance in the prevention of primary cardiovascular diseases with
      lovastatine. PRELOVAS study].
AB  - BACKGROUND AND OBJECTIVE: Our objective was to compare the therapeutic compliance
      in two groups of patients treated with lovastatine for the prevention of
      cardiovascular diseases in clinical practice. PATIENTS AND METHOD: Observational,
      prospective and multi-centre study carried out in patients who attended primary
      care and had a clinical indication to follow treatment with lovastatine for the
      prevention of cardiovascular diseases. Four visits were carried out (baseline, at
      4-6 weeks, at 6 and 12 months). In the baseline visit, clinical and
      sociodemographic variables were registered. In visit 2, the investigator counted
      the number of pills the patients had taken, which together with the results of
      the Morisky Green Questionnaire allowed him to classify the patients into two
      groups: Group A (non-compliant patient) and B (compliant patient). Group A
      received medical advice in order to increase the adherence to treatment. RESULTS:
      A total of 815 subjects with indication of lipid-lowering treatment were
      involved. At the 6 month of follow up, 22% of the subjects from Group A and 63%
      from Group B had improved their adherence, 38% of the subjects of the group B
      maintained a good therapeutic compliance during the whole study and 12% of the
      group A subjects who came up to the final visit improved their compliance during
      the whole study (p < 0.05). Subjects who showed good compliance with the lipid
      lowering treatment along 12 months registered lesser values of cholesterol (128
      mg/dl) (p < 0.005). CONCLUSIONS: It is important to identify non-compliant
      patients at the beginning of the treatment with lipid-lowering treatment. That
      makes possible to implement from the very beginning therapeutic measures aimed at
      improving the therapeutic compliance and allows at the same time to achieve a
      greater therapeutic effectiveness.

PMID- 15563817
TI  - [Impact factor of the Spanish medical journals].
AB  - BACKGROUND AND OBJECTIVE: The 2001 edition of the Journal Citation Reports (JCR)
      includes only 13 Spanish medical journals. The impact factor (IF) of the rest of
      Spanish medical journals is unknown. The aim of this study is to determine the IF
      of the main Spanish medical journals, taking also into account the references
      from journals not covered by the SCI. MATERIAL AND METHOD: A set of 87 Spanish
      medical journals was selected from the national database IME and other
      international databases. All citable articles published in these journals in 2001
      were analyzed, extracting their bibliographic references to articles published in
      1999, 2000 and 2001. The indicators obtained for each journal were the number of
      cites, the IF and the immediacy index. RESULTS: Among the 87 source journals, 74
      were not included in the JCR. From them, 5,388 bibliographic references were
      examined, identifying the journals cited. Final indicators were obtained adding
      these results to the ones obtained by using the Science Citation Index. The most
      cited journal was Medicina Clinica (768 cites), and the highest IF were attained
      by Histology and Histopathology (IF = 1.866), International Journal of
      Developmental Biology (IF = 1.654) and Medicina Clinica (IF = 1.125).
      CONCLUSIONS: This work has permitted to obtain the IF of 87 Spanish medical
      journals. Already detected in previous works, the leadership of the journal
      Medicina Clinica in Spanish medicine is confirmed. Spanish medical journals
      published in English have received a small number of cites from the ones
      published in Spanish. A low impact factor is not necessarily related to lack of
      quality, merit or relevance.

PMID- 15563818
TI  - [Determination of the overall cardiovascular risk: an utopia?].

PMID- 15563819
TI  - [Systemic lupus erythematosus and accelerated atheromatosis].

PMID- 15563820
TI  - [Hypertension and metabolic syndrome].

PMID- 15563821
TI  - [Undifferentiated, overlapping and mixed connective tissue diseases].
AB  - Mixed connective tissue disease (MCTD), undifferentiated connective tissue
      disease and overlap syndromes are autoimmune systemic diseases that must be
      differentiated. Antibodies against the U1-ribonucleoprotein complex --spliceosome
      - allows the diagnosis of mixed connective tissue disease. Links between the
      immunologic and clinical phenomena are emerging. Longitudinal studies of patients
      with MCTD highlight the impact of pulmonary hypertension and contribute to define
      the disease. Immunogenetic studies hold MCTD as an independent disease.

PMID- 15563822
TI  - [About terminology: How should we call Lynch syndrome in Spanish?].

PMID- 15563823
TI  - [Ekbom's syndrome and diabetes mellitus].

PMID- 15563824
TI  - ["The lord of the annealings". PCR and medical language].

PMID- 15563825
TI  - [Giant cell arteritis and De Quervain thyroiditis].

PMID- 15563827
TI  - The DEK protein--an abundant and ubiquitous constituent of mammalian chromatin.
AB  - The protein DEK is an abundant and ubiquitous chromatin protein in multicellular
      organisms (not in yeast). It is expressed in more than a million copies/nucleus
      of rapidly proliferating mammalian cells. DEK has two DNA binding modules of
      which one includes a SAP box, a sequence motif that DEK shares with a number of
      other chromatin proteins. DEK has no apparent affinity to specific DNA sequences,
      but preferentially binds to superhelical and cruciform DNA, and induces positive
      supercoils into closed circular DNA. The available evidence strongly suggests
      that DEK could function as an architectural protein in chromatin comparable to
      the better known classic architectural chromatin proteins, the high-mobility
      group or HMG proteins.

PMID- 15563828
TI  - Testis-specific transcriptional control.
AB  - In the testis, tissue-specific transcription is essential for proper expression
      of the genes that are required for the reproduction of the organism. Many testis
      specific genes are required for mitotic proliferation of spermatogonia,
      spermatocytes undergoing genetic recombination and meiotic divisions, and
      differentiation of haploid spermatids. In this article we describe some of the
      genes that are transcribed in male germinal cells and in non-germinal testis
      cells. Because significant progress has been made in examination of promoter
      elements and their cognate transcription factors that are involved in controlling
      transcription of the testis-specific linker histone H1t gene in primary
      spermatocytes, this work will be reviewed in greater detail. The gene is
      transcriptionally active in spermatocytes and repressed in all other germinal and
      non-germinal cell types and, therefore, it serves as a model for study of
      regulatory mechanisms involved in testis-specific transcription.

PMID- 15563830
TI  - How strong is the case for regulation of the initiation step of translation by
      elements at the 3' end of eukaryotic mRNAs?
AB  - The belief that initiation of translation requires communication between the 5'
      and 3' ends of the mRNA guides--or misguides--the interpretation of many
      experiments. The closed-loop model for initiation creates the expectation that
      sequences at the 3' end of eukaryotic mRNAs should regulate translation. This
      review looks closely at the evidence in three prominent cases where such
      regulation is claimed. The mRNAs in question encode 15-lipoxygenase,
      ceruloplasmin, and histones. Vertebrate histone mRNAs lack a poly(A) tail,
      instead of which a 3' stem-loop structure is said to promote translation by
      binding a protein which purportedly binds initiation factors. The proffered
      evidence for this hypothesis has many flaws. Temporal control of 15-lipoxygenase
      production in reticulocytes is often cited as another well-documented example of
      translational regulation via the 3' untranslated region, but inspection of the
      evidence reveals significant gaps and contradictions. Solid evidence is lacking
      also for the idea that a ribosomal protein binds to and shuts off translation of
      ceruloplasmin mRNA. Some viral RNAs that lack a poly(A) tail have alternative 3'
      structures which are said to promote translation via circularization of the mRNA,
      but in no case has this been shown convincingly. Interpretation of many
      experiments is compromised by possible effects of the 3' structures on mRNA
      stability rather than translation. The functional-half-life assay, which is often
      employed to rule out effects on mRNA stability, might not be adequate to settle
      the question. Other issues, such as the possibility of artifacts caused by
      overexpression of RNA-binding proteins, can complicate studies of translational
      regulation. There is no doubt that elements at the 3' end of eukaryotic mRNAs can
      regulate gene expression in a variety of ways. It has not been shown
      unequivocally that one of these ways involves direct participation of the 3'
      untranslated region in the initiation step of translation.

PMID- 15563829
TI  - Lineage-specific and ubiquitous biological roles of the mammalian transcription
      factor LSF.
AB  - Transcriptional regulation in mammalian cells is driven by a complex interplay of
      multiple transcription factors that respond to signals from either external or
      internal stimuli. A single transcription factor can control expression of
      distinct sets of target genes, dependent on its state of post-translational
      modifications, interacting partner proteins, and the chromatin environment of the
      cellular genome. Furthermore, many transcription factors can act as either
      transcriptional repressors or activators, depending on promoter and cellular
      contexts [Alvarez, M., Rhodes, S.J., Bidwell, J.P., 2003. Context-dependent
      transcription: all politics is local. Gene 313, 43-57]. Even in this light, the
      versatility of LSF (Late SV40 Factor) is remarkable. A hallmark of LSF is its
      unusual DNA binding domain, as evidenced both by lack of homology to any other
      established DNA-binding domains and by its DNA recognition sequence. Although a
      dimer in solution, LSF requires additional multimerization with itself or partner
      proteins in order to interact with DNA. Transcriptionally, LSF can function as an
      activator or a repressor. It is a direct target of an increasing number of signal
      transduction pathways. Biologically, LSF plays roles in cell cycle progression
      and cell survival, as well as in cell lineage-specific functions, shown most
      strikingly to date in hematopoietic lineages. This review discusses how the
      unique aspects of LSF DNA-binding activity may make it particularly susceptible
      to regulation by signal transduction pathways and may relate to its distinct
      biological roles. We present current progress in elucidation of both tissue
      specific and more universal cellular roles of LSF. Finally, we discuss suggestive
      data linking LSF to signaling by the amyloid precursor protein and to Alzheimer's
      disease, as well as to the regulation of latency of the human immunodeficiency
      virus (HIV).

PMID- 15563831
TI  - Structural features of hematopoiesis-specific RhoH/ARHH gene: high diversity of
      5'-UTR in different hematopoietic lineages suggests a complex post
      transcriptional regulation.
AB  - The hematopoiesis-specific RhoH gene is thought to be deregulated in B-cell non
      Hodgkin's lymphoma (B-NHL), by either a chromosomal translocation or mutations,
      which affect its 5' regulatory region. The encoded Rho protein, always GTP-bound
      in vivo, was hypothesized to behave as a Rac antagonist. Extensive expression
      analysis allowed the detection of RhoH transcripts in all hematopoietic lineages
      (lymphoid, erythroid, myeloid), with a high level in lymphoid cells. To initiate
      investigations on the molecular mechanisms that regulate RhoH gene expression,
      Race-PCR and primer extension were conducted in the B-cell line Raji, which
      allowed (i) the establishment of RhoH complex intron/exon organization and (ii)
      the detection of several transcription initiation sites. In addition, a high 5'
      end heterogeneity of RhoH mRNAs was observed, due to alternative splicing of some
      5' exons and to the use of these different transcription start sites. RT-PCR
      analysis led to the identification of this 5' end heterogeneity in different
      hematopoietic lineages. Discrepancies were particularly observed between B and T
      cells, due to an alternative splicing of one 5' exon (1b), which might be an
      important element in RhoH gene regulation. Such specific features have never been
      described for any Rho family member gene. They provide a molecular basis to study
      complex mechanisms involved in the control of RhoH expression.

PMID- 15563832
TI  - A novel human homologue of Drosophila polycomblike gene is up-regulated in
      multiple cancers.
AB  - Polycomb group (PcG) proteins function to maintain the stable epigenetic
      repression of homeotic genes and other important developmental and cell cycle
      regulatory genes. Such maintenance establishes a form of cellular memory for its
      identity or state of differentiation. Accumulating evidence indicates that
      perturbation of this transcriptional memory may be required for tumor progression
      and may represent a hallmark of cancer. We have identified a novel gene encoding
      a human homologue of the Drosophila polycomblike protein, hPCL3. Through
      alternative polyadenylation and/or splicing, the gene encodes two nuclear
      proteins, hPCL3S and hPCL3L. Both proteins repressed transcription upon
      recruitment to the proximity of an HSV-tk promoter by a Gal4 DNA binding domain.
      Interestingly, the products of the hPCL3 gene, particularly the short form,
      hPCL3S, are markedly overexpressed in many types of cancers, including colon,
      skin, lung, rectal, cervical, uterus, and liver cancers. This increase in
      expression correlated with tumor progression. Both hPCL3S and hPCL3L messages
      were increased dramatically in most cell lines derived from various stages of
      melanoma and glioma tumor progression. Thus, our data link PcG deregulation to
      the progression of multiple cancers and may have important implications for
      unraveling the mechanisms of tumor progression.

PMID- 15563833
TI  - Bex3 associates with replicating mitochondria and is involved in possible growth
      control of F9 teratocarcinoma cells.
AB  - Bex3 expression and possible function in growth control were studied. It was
      expressed in a limited number of organs, including gonads and hippocampal regions
      of the brain. Visualized by deconvolution microscopy as a GFP-fusion protein in
      F9 teratocarcinoma cells, Bex3 localized, along with concentrations of actin, at
      perinuclear mitochondria that were undergoing active DNA replication. Bex3
      association with mitochondria required a nuclear export signal (NES) and the C
      terminal four amino acids (CaaX box), and siRNA reduction of Bex3 levels led to
      slow or negligible growth rates of the F9 cells. Thus, Bex3 may be required in
      target tissues for mitochondrial function at a distinct phase of the cellular
      growth cycle.

PMID- 15563834
TI  - Efficient somatic gene targeting in the lymphoid human cell line DG75.
AB  - Among the different approaches used to define the function of a protein of
      interest, alteration and/or deletion of its encoding gene is the most direct
      strategy. Homologous recombination between the chromosomal gene locus and an
      appropriately designed targeting vector results in an alteration or knockout of
      the gene of interest. Homologous recombination is easily performed in yeast or in
      murine embryonic stem cells, but is cumbersome in more differentiated and diploid
      somatic cell lines. Here we describe an efficient method for targeting both
      alleles of a complex human gene locus in DG75 cells, a cell line of lymphoid
      origin. The experimental approach included a conditional knockout strategy with
      three genotypic markers, which greatly facilitated the generation and phenotypic
      identification of targeted recombinant cells. The vector was designed such that
      it could be reused for two consecutive rounds of recombination to target both
      alleles. The human DG75 cell line appears similar to the chicken DT40 pre B-cell
      line, which supports efficient homologous recombination. Therefore, the DG75 cell
      line is a favorable addition to the limited number of cell lines amenable to gene
      targeting and should prove useful for studying gene function through targeted
      gene alteration or deletion in human somatic cells.

PMID- 15563835
TI  - Single-chain integration host factors as probes for high-precision nucleoprotein
      complex formation.
AB  - Integration host factor (IHF) is a heterodimeric, site-specific DNA-binding and
      DNA-bending protein from Escherichia coli. It is involved in high-precision DNA
      transactions where it serves as a key architectural component of specialized
      nucleoprotein structures (snups). We described recently a novel approach for
      protein engineering using a single polypeptide chain IHF, termed scIHF2, as a
      first example. ScIHF2 is made up of the alpha subunit of IHF which was inserted
      into the beta subunit at peptide bond Q39/G40 via two short linkers. The monomer
      behaves very similarly to the heterodimeric, parental IHF in biochemical and
      functional assays. Here, we describe an extension of this approach in which we
      shortened either one or both linkers by one amino acid, thereby generating three
      new variants termed scIHF1, 3, and 4. These variants exhibit distinct DNA-binding
      properties, different phenotypes in site-specific integrative and excisive
      recombination by phage lambda integrase in vitro, as well as in pSC101
      replication assays in a DeltaIHF E. coli host. We also introduced a K45E
      substitution within the alpha domain of scIHF3 and based on electrophoretic
      mobility shift assays (EMSAs), argue that it significantly changes the DNA
      trajectory within the protein-DNA complex. Our results indicate that IHF's
      pleiotropic roles in DNA transactions inside E. coli require different types of
      high-precision DNA architectural activities. The scIHF variants described here
      will help to explore further how flexible these requirements are.

PMID- 15563836
TI  - Analysis and manipulation of amphotericin biosynthetic genes by means of modified
      phage KC515 transduction techniques.
AB  - Amphotericin B is a medically important antifungal antibiotic that is produced by
      Streptomyces nodosus. Genetic manipulation of this organism has led to production
      of the first amphotericin analogues by engineered biosynthesis. Here, these
      studies were extended by sequencing the chromosomal regions flanking the
      amphotericin polyketide synthase genes, and by refining the phage KC515
      transduction method for disruption and replacement of S. nodosus genes. A hybrid
      vector was constructed from KC515 DNA and the Escherichia coli plasmid pACYC177.
      This vector replicated as a plasmid in E. coli and the purified DNA yielded phage
      plaques on Streptomyces lividans after polyethylene glycol (PEG)-mediated
      transfection of protoplasts. The left flank of the amphotericin gene cluster was
      found to include amphRI, RII, RIII and RIV genes that are similar to regulatory
      genes in other polyene biosynthetic gene clusters. One of these regulatory genes,
      amphRI, was found to have a homologue, amphRVI, located in the right flank at a
      distance of 127 kbp along the chromosome. However, disruption of amphRVI using
      the hybrid vector had no effect on the yield of amphotericin obtained from
      cultures grown on production medium. The hybrid vector was also used for precise
      deletion of the DNA coding for two modules of the AmphC polyketide synthase
      protein. Analysis by UV spectrophotometry revealed that the deletion mutant
      produced a novel pentaene, with reduced antifungal activity but apparently
      greater water-solubility than amphotericin B. This shows the potential for use of
      the new vector in engineering of this and other biosynthetic pathways in
      Streptomyces.

PMID- 15563837
TI  - YY1 is involved in RANKL-induced transcription of the tartrate-resistant acid
      phosphatase gene in osteoclast differentiation.
AB  - Receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL), a
      critical activator of osteoclast differentiation, plays a pivotal role in
      tartrate-resistant acid phosphatase (TRAP) gene expression. Previously, we showed
      that upstream stimulatory factors (USF) 1 and 2 are implicated in the RANKL
      induced TRAP transcriptional activation via a 12-bp USF binding site in the TRAP
      promoter. In that study, we also demonstrated that a RANKL-induced nuclear
      protein binds to a 50-bp oligonucleotide (Oligo IV) corresponding to a distinct
      TRAP promoter region. Here we report the identification and functional
      characterization of the nuclear protein binding to Oligo IV. We identified a 21
      bp sequence CTGTTTATGATGGCGAGGGGG in Oligo IV that specifically binds the RANKL
      induced nuclear protein from RAW264.7 cells by performing a series of competition
      assays. Computer analysis of the 21-bp sequence revealed that the sequence
      contains a putative Yin Yang 1 (YY1) binding site overlapped with a putative
      activator protein-2 (AP-2) binding site. Competition and supershift assays
      indicated that the nuclear protein binding to the 21-bp sequence is YY1, not AP
      2. Functionally, mutation of the YY1-binding site resulted in a reduction in the
      RANKL-induced TRAP transcription in RAW264.7 cells, demonstrating that YY1
      positively regulates RANKL-induced TRAP transcriptional activation. In
      conclusion, our data demonstrated that YY1 plays a functional role in RANKL
      mediated TRAP gene expression during osteoclast differentiation.

PMID- 15563838
TI  - CCC CGA is a weak translational recoding site in Escherichia coli.
AB  - Previously published experiments had indicated unexpected expression of a control
      vector in which a beta-galactosidase reporter was in the +1 reading frame
      relative to the translation start. This control vector contained the codon pair
      CCC CGA in the zero reading frame, raising the possibility that ribosomes
      rephased on this sequence, with peptidyl-tRNA(Pro) pairing with CCC in the +1
      frame. This putative rephasing might also be exacerbated by the rare CGA Arg
      codon in the second position due to increased vacancy of the ribosomal A-site. To
      test this hypothesis, a series of site-directed mutants was constructed,
      including mutations in both the first and second codons of this codon pair. The
      results show that interrupting the continuous run of C residues with synonymous
      codon changes essentially abolishes the frameshift. Further, changing the rare
      Arg codon to a common Arg codon also reduces the frequency of the frameshift.
      These results provide strong support for the hypothesis that CCC CGA in the zero
      frame is indeed a weak translational frameshift site in Escherichia coli, with a
      1-2% efficiency. Because the vector sequence also contains another CCC triplet in
      the +1 reading frame starting within the next codon after the CGA, our data also
      support possible contribution to expression of a +7 nucleotide ribosome hop into
      the same +1 reading frame. We also confirm here a previous report that CCC UGA is
      a translational frameshift site, in these experiments, with about 5% efficiency.

PMID- 15563839
TI  - Change in the expressed gene patterns of the wing disc during the metamorphosis
      of Bombyx mori.
AB  - The present study was conducted to clarify what occurs during the metamorphosis
      of the imaginal disc in insects. To understand the metamorphosis on a molecular
      level, the changes in expression profiles in the imaginal disc during
      metamorphosis were investigated. For this purpose, we constructed cDNA libraries
      from four different stages of wing discs of Bombyx mori, sequenced about 1000
      cDNAs randomly collected from each library, and constructed a database of
      expressed sequence tags (EST). The morphological changes and expression profiles
      from EST were compared during those four stages. Microarray analysis was applied
      to quantify the expression of each gene in each stage in order to confirm whether
      the expression of the genes identified from EST was induced by 20-hydroxyecdysone
      (20E) in a stage-specific manner. Wing discs showed dynamic morphogenesis in 4-5
      days during the preparatory stage of metamorphosis, which was under the control
      of an ecdysteroid. Different expressed profiles were observed in each of the four
      different stages by comparison of each EST clone. These profiles reflected the
      morphological changes of the Bombyx wing disc during metamorphosis. The results
      of expression profiles from the four stages suggested that the V4 stage was cell
      proliferating; W0, proliferating and the beginning of differentiation; W2,
      morphologically changing; W3, cuticle secreting. Microarray analysis showed the
      effectiveness of its application on 20E induction of genes in wing discs. The
      wing disc of B. mori is an exceptionally suitable system for understanding the
      relationship between morphological changes and the distribution of mRNA.

PMID- 15563840
TI  - Molecular characterization of two novel isoforms of the human calcitonin
      receptor.
AB  - Calcitonin inhibits bone resorption by acting on osteoclasts via a specific
      receptor. The calcitonin receptor (CTR) is also found in many other normal and
      malignant tissues and cell lines. It has been cloned and sequenced in several
      species including humans. It belongs to a subclass of seven-transmembrane G
      protein-coupled receptors. Four human CTR (H-CTR) isoforms generated by
      alternatively spliced mRNA have previously been described. Two H-CTR encoding
      DNAs containing an unidentified 50-bp insert are now reported from T47D cells.
      The 50-bp insert corresponds to a DNA region located between exon 9 and exon 10,
      and appears to originate from an alternative splicing process. The two H-CTR
      cDNAs encode 274 and 290 aa long isoforms. Both are deleted from the putative
      fourth transmembrane domain to C-tail. They differ by the presence (H-CTR5) or
      absence (H-CTR6) of a previously known 16-aa insert in the putative first
      intracellular loop. Cell- and tissue-distribution analysis using RT-PCR
      demonstrates that the shorter one, HCTR6, is more prevalent. The mRNA of both
      isoforms was detected in giant cell tumor, whereas only H-CTR6 mRNA was detected
      in TT cells and kidney tissue. Neither H-CTR5 nor H-CTR6 could be detected in
      peripheral blood mononuclear cells cultured in the presence of RANKL, in MCF7
      cells, and in cortical brain and ovarian tissues. When H-CTR6 was transiently
      expressed in HEK293 cells, CT failed to induce production of cAMP or to bind to
      the receptor. These suggest either an intrinsic loss of ligand binding function,
      or an altered intracellular trafficking. Our findings therefore indicate the
      existence of two novel splice variants of the H-CTR and confirm that multiple
      splicing patterns could be involved in the post-transcriptional regulation of the
      gene.

PMID- 15563841
TI  - Functional analysis of the NPDC-1 gene.
AB  - Mouse NPDC-1 (Neural Proliferation Differentiation and Control-1) is specifically
      expressed in neural cells when they stop dividing and start to differentiate. The
      NPDC-1 protein has been shown to interact with the E2F1 transcription factor, D
      type cyclins and Cdk2. Immunocytochemical studies and subcellular fractionation
      of rat brains disclosed a partial colocalization of NPDC-1 with synaptic vesicle
      proteins, suggesting additional functional interactions. Here, we report the
      characterization of the mouse and human genes that were found to display very
      similar structures. We mapped the human gene to chromosome 9q34.3. No obvious
      pathological defect has been previously linked to this region. In order to gain
      further insights into its function(s), we generated null mice for the NPDC-1
      gene. We did not detect any macroscopic phenotypical defect. Analysis of the
      upstream sequence of the mouse NPDC-1 gene delineated two regions involved in its
      negative and positive transcriptional regulation. Evidence for the regulation of
      NPDC-1 by Krox family transcription factors is presented.

PMID- 15563842
TI  - Functional variability of cagA gene in Japanese isolates of Helicobacter pylori.
AB  - CagA protein of Helicobacter pylori is injected into the epithelium, where CagA
      undergoes tyrosine phosphorylation and activates proliferation signals. However,
      the importance of these CagA activities for pathogenesis has yet to be resolved.
      The aim of this study is to analyze the genetic and functional variability of
      cagA gene of clinical strains in relation to gastric diseases. Thirty-six H.
      pylori strains were isolated from Japanese patients with various gastric diseases
      and examined. All 36 strains were found to contain cagA and cagE gene and to
      induce CagA phosphorylation upon infection. The intensity of CagA phosphorylation
      expressed in HeLa cells by transfection was highly correlated to the number of R1
      region. The phosphorylation intensity was slightly higher in strains from chronic
      atrophic gastritis (CG); however, the differences were not statistically
      significant. These CagA proteins also activated the serum response element (SRE)
      reporter by 5- to 14-fold, above the level of the control. CagA proteins which
      lack R2 or R3 region exhibited smaller ability for SRE activation. The average of
      SRE activation was slightly higher in strains from cases of gastric cancer (GC;
      11.4+/-1.6), MALT lymphoma (ML; 10.7+/-1.0), and chronic atrophic gastritis (CG;
      11.2+/-1.6) than in those of duodenal ulcer (DU; 8.3+/-1.9) or gastric ulcer (GU;
      9.0+/-1.1). In summary, most Japanese H. pylori strains contained CagA transport
      system and induced CagA phosphorylation, and the levels of the intensity of
      phosphorylation and the ability to induce SRE varied among strains. Although the
      association between CagA activities and disease outcome shown in this study is
      not very strong, variety of CagA structure, which induces variable activities,
      may be one of the reasons why H. pylori induces distinct diseases on host.

PMID- 15563843
TI  - Transcriptional activity and substrate recognition of cyclin T2 from P-TEFb.
AB  - Transcriptional elongation by RNA polymerase II (RNAPII) is regulated by the
      positive transcription elongation factor b (P-TEFb), which contains Cdk9 and a C
      type cyclin (CycT1, CycT2a, CycT2b, or CycK). Whereas their N-terminal cylin
      boxes are almost identical, the C-terminal sequences of CycT1 and CycT2 are
      divergent. Previously, a histidine-rich stretch in CycT1 was found to bind the
      CTD of RNAPII and direct the transcriptional activity of this P-TEFb complex when
      tethered artificially to DNA. The global repressor PIE-1 from C. elegans blocked
      its effects. In this study, C-terminal truncations of CycT2 past its histidine
      rich stretch, to a leucine-rich region next to its cyclin boxes, still maintained
      appreciable transcriptional activity. Moreover, this domain bound RNAPII via its
      CTD and PIE-1 blocked its effects. Thus, CycT2 not only contains two domains that
      target RNAPII but this substrate recognition is necessary for its transcriptional
      activity via DNA.

PMID- 15563844
TI  - Consecutive gene deletions in Mycobacterium smegmatis using the yeast FLP
      recombinase.
AB  - Mycobacteria contain a large number of redundant genes whose functions are
      difficult to analyze in mutants, because there are only two efficient resistance
      markers available for allelic exchange experiments. We have established a system
      based on the Flp recombinase of the yeast Saccharomyces cerevisiae for use in the
      nonpathogenic model organism Mycobacterium smegmatis. This system consists of a
      hygromycin resistance cassette flanked by two Flp recognition targets (FRT) in
      direct orientation and a curable plasmid for expression of the flp gene. The FRT
      hyg-FRT cassette was used on a suicide plasmid and on a conditionally replicating
      plasmid to delete two of the four known porin genes of M. smegmatis, mspA and
      mspC, respectively, by homologous recombination. The hyg gene was specifically
      removed from the chromosome of both mutants upon expression of the flp gene.
      Based on the marker-less mspC mutant strain, a double knock-out mutant lacking
      also mspA was obtained using the same strategy. Thus, by a fast and efficient two
      step procedure, each of the porin genes was replaced by a single FRT site, which
      can be further used for site-specific integration. These results show that the
      Flp/FRT system is a suitable genetic tool for constructing unmarked mutations and
      for the analysis of redundant genes by consecutive gene deletions in M.
      smegmatis.

PMID- 15563845
TI  - Identification and cloning of genes displaying elevated expression as a
      consequence of metastatic progression in human melanoma cells by rapid
      subtraction hybridization.
AB  - Although extensively investigated, the complete repertoire of genes associated
      with and causative of metastasis remain largely unknown. We developed an
      efficient approach for identifying differentially expressed genes that involves
      rapid subtraction hybridization (RaSH) of cDNA clones prepared from two cell
      populations, a driver and a tester. This RaSH approach has previously documented
      high sensitivity and effectiveness in identifying genes that are differentially
      expressed as a function of induction of terminal differentiation in human
      melanoma cells, resistance or sensitivity to human immunodeficiency virus-1 (HIV
      1) infection of human T cells and perturbation in gene expression in normal human
      fetal astrocytes infected with HIV-1 or treated with HIV-1 gp120 viral envelope
      glycoprotein or tumor necrosis factor-alpha (TNF-alpha). In the present study,
      RaSH has been applied to a metastatic melanoma model, which mimics the early
      events of metastasis in humans, comprising weakly metastatic vs. immunosuppressed
      newborn rat-selected highly metastatic variants. This has now resulted in the
      identification of eight genes displaying elevated expression in the high
      metastatic variants vs. normal immortal melanocytes or weakly metastatic parental
      clones. These include six known genes, 67-kDa laminin receptor (67LR), endothelin
      receptor B (ENDRB), Na+/K+-ATPase, Ku antigen, interleukin-receptor-associated
      kinase-1 (IRAK-1) and ribosomal protein RPLA, which may contribute to the complex
      process of melanoma metastasis. Additionally, two unknown genes (not reported in
      current databases) that may also impact on the metastatic phenotype have also
      been identified. These studies provide additional support of the use of the RaSH
      approach, in this application in the context of closely related variant cell
      lines with different metastatic potential, for effective differential gene
      identification and elucidate eight previously unrecognized genes whose role in
      melanoma progression to metastatic competence can now be scrutinized.

PMID- 15563846
TI  - Cloning and characterization of a forkhead transcription factor gene, FoxO1a,
      from thirteen-lined ground squirrel.
AB  - This research analyzes the regulation of ischemic tolerance in hibernating
      thirteen-lined ground squirrels (Spermophilus tridecemlineatus). Hibernation is
      studied because it represents a unique state of reversible suspended animation
      associated with tolerance to an otherwise lethal reduction of core body
      temperature and metabolism. An integral aspect of hibernation is the profound
      decrease of cerebral perfusion without neurological damage. As such, hibernation
      serves as a model for studying natural tolerance to brain ischemia.
      Identification of regulatory mechanisms that control hibernation in ground
      squirrels may guide efforts to develop improved treatments for stroke and brain
      trauma. It was previously shown that phosphorylation of Akt (protein kinase B),
      an insulin-like growth factor-regulated serine/threonine kinase, was
      significantly reduced as was its kinase activity in hibernating thirteen-lined
      ground squirrels. Here we studied the forkhead (FH) in rhabdomyosarcoma (FKHR)
      transcription factor, which is controlled by Akt signaling and is involved in
      regulating cell cycle progression and cell death. A cDNA derived from brains of
      S. tridecemlineatus, encoding a specific FKHR transcription factor, FoxO1a, was
      cloned and sequenced, and the amino acid sequence of the protein was deduced.
      FoxO1a is composed of 653 amino acids and has a predicted molecular mass of 69.4
      kilodaltons (kDa). Here, for the first time, we report the contrary expression of
      phosphorylation of two members in the insulin-like growth factor signaling
      pathway during hibernation (i.e., phosphorylated FKHR was significantly up
      regulated as phosphorylation of its upstream kinase, Akt, was significantly down
      regulated). Further study is required to identify the possible connection between
      FoxO1a and Akt activity and the possible of such interactions in hibernation.

PMID- 15563847
TI  - The identification of genes from the oyster Crassostrea gigas that are
      differentially expressed in progeny exhibiting opposed susceptibility to summer
      mortality.
AB  - Summer mortality associated with juveniles of the oyster Crassostrea gigas is
      probably the result of a complex interaction between the host, pathogens and
      environmental factors. Genetic variability in the host appears to be a major
      determinant in its sensitivity to summer mortality. Previously, divergent
      selection criteria based on summer survival have been applied to produce oyster
      families with resistant and susceptible progeny. In this paper, we describe the
      use of suppression subtractive hybridization to generate 150 C. gigas clones that
      were differentially regulated between resistant and susceptible F2 progeny. The
      nucleotide sequence of these clones was determined. In 28%, the inferred amino
      sequence was found to match the products of known genes, 14% matched hypothetical
      proteins and a further 14% appeared to contain open reading frames (ORFs) whose
      product had no obvious homologue in the nucleotide databases. It has been
      hypothesized that differences exist in the level of energy generation and immune
      function between resistant and susceptible progeny. In light of this, clones
      encoding homologues of cavortin, cyclophilin, isocitrate dehydrogenase, sodium
      glucose cotransporter, fatty acid binding protein, ATPase H+ transporting
      lysosomal protein, precerebellin, and scavenger receptor were analyzed by real
      time PCR. These transcripts were induced in resistant progeny when compared to
      their susceptible counterparts. A bacterial challenge of oysters resulted in the
      suppression of six of these transcripts in only those that were resistant to
      summer mortality. This study has identified potential candidates for further
      investigation into the functional basis of resistance and susceptibility to
      summer mortality.

PMID- 15563848
TI  - Genomic structure and expression analysis of the mouse testis-specific ribbon
      protein (Trib) gene.
AB  - During our analyses of genes required for the development and function of the
      mouse gonads, we identified a novel testis-specific mRNA, transcribed from a gene
      that we have named testis-specific ribbon protein (Trib). In the mouse, Trib is
      located on chromosome 15, overlapping with and transcribed in the opposite
      orientation of the meiosis specific gene Smc1beta. The deduced amino acid
      sequence of testis ribbon (TRIB) protein is highly conserved between human,
      mouse, and rat and contains the ribbon motifs found in the largely
      uncharacterized microtubule ribbon protein ribbon43a (RIB43A). We show by
      Northern blot analyses and reverse transcription-polymerase chain reaction (RT
      PCR) that Trib mRNA is specifically expressed in the adult testis. In situ
      hybridization indicates that Trib is expressed solely in germ cells during the
      leptotene-pachytene stages of spermatogenesis. The high level of evolutionary
      conservation and the cellular and temporal expression suggest that Trib may be
      required for mouse spermatogenesis and male fertility. Here, we describe the
      genomic structure and expression profile of mouse Trib and compare its homology
      with other ribbon proteins.

PMID- 15563849
TI  - Life with consequences of breast cancer: pregnancy during and after endocrine
      therapies.

PMID- 15563850
TI  - Tamoxifen and pregnancy.
AB  - Women are conventionally advised to stop tamoxifen before attempting pregnancy.
      The risks of congenital malformations or late teratogenic manifestations in
      adulthood are unknown. Following an informed discussion about the uncertainties
      of tamoxifen exposure on pregnancy women should be offered the choice whether to
      continue or stop tamoxifen before attempting pregnancy. An unexpected pregnancy
      in a women taking tamoxifen could continue if the pregnant woman accepts the
      possibility of a teratogenic effect that tamoxifen could have on the fetus.

PMID- 15563851
TI  - Radioresistance in carcinoma of the breast.
AB  - Radiotherapy plays an important role in the management of breast cancer. Whilst
      its role in achieving local control following surgery in patients with early
      stage cancer is well established, there is still unclear evidence to explain the
      factors governing radioresistance in patients who develop recurrences both in the
      breast and axilla. Radiotherapy induces damage to the DNA. Various cell cycle
      damage check points and DNA damage repair pathways have been demonstrated. Ataxia
      telangiectasia mutant (ATM) kinase, which is a member of phosphatidylinositol-3
      kinase (PI-3K) family appears to play a central role in DNA damage check point
      pathways. Over-expression of Insulin like growth factor-I receptor (IGF-IR),
      Human Epidermal Growth factor receptors (HERS), Vascular Endothelial growth
      factor (VEGF) on the cell surface and increased concentration of Epidermal Growth
      factor in the extracellular fluid have been associated with radioresistance.
      Specific genes such as p53, BRCA, Bcl-2 and chromosomal characteristics like
      telomere lengths have also been identified as playing significant roles in
      radiation responsiveness of a cell. This article reviews the current data on
      general principles of radiotherapy, the cellular mechanisms that operate in
      response to radiation damage and various molecular markers, intranuclear and
      extranuclear which have been demonstrated to influence radiation sensitivity in
      breast cancer cells.

PMID- 15563852
TI  - Ductal carcinoma in situ presenting as microcalcifications: the effect of
      stereotactic large-core needle biopsy on surgical therapy.
AB  - The aim of this investigation was to study the efficacy of surgical therapy in
      patients with non-palpable ductal carcinoma in situ (DCIS) presenting as
      microcalcifications diagnosed by means of stereotactic large-core needle biopsy
      (SCNB). This is a retrospective study with a historical control group within a 12
      year period. Two groups of consecutive patients diagnosed with DCIS (1991-2002)
      by means of needle-localised open breast biopsy (NLBB, n=49) and SCNB (n=51) were
      studied. Both groups were comparable for clinical, radiological and pathological
      characteristics. The therapeutic interval (time from presentation to definitive
      of therapy) was 62-days in the SCNB group versus 32-days in the NLBB group
      (p<0.001). In the SCNB group fewer surgical procedures were required for
      completion of surgical therapy (p=0.006) and after local excision the surgical
      margins were more often tumour free (p=0.002). It is postulated that the need for
      fewer surgical procedures and the greater frequency of tumour-free margins after
      local excision may be attributable to SCNB.

PMID- 15563853
TI  - Breast cancer management: the perspective of general practitioners in inner and
      eastern Melbourne.
AB  - This study sought to explore general practitioners' (GPs') experience with
      specialist breast services and to identify their communication, education and
      resource requirements regarding care of the breast cancer patient, by means of a
      self-administered questionnaire distributed to 450 GPs in inner and eastern
      Melbourne. Twenty-three per cent of questionnaires were returned. On average, GPs
      had one patient newly diagnosed with breast cancer per year. GPs were most likely
      to refer symptomatic patients to a private specialist breast surgeon. Their
      referral pattern was largely influenced by previous experience of referral to the
      service. Communication with specialist breast services was generally satisfactory
      during the initial stages of diagnosis and treatment; however discharge
      communication, phone communication with specialists, and admission notification
      was less satisfactory. When given a list of topics in which GPs may require
      further education, 65% of respondents identified "Recent advances in breast
      cancer management" as an area of interest, and the majority requested a directory
      listing breast services in their local area.

PMID- 15563854
TI  - A needle-localised open-breast biopsy for nonpalpable breast lesions should not
      be performed for diagnosis.
AB  - BACKGROUND: The achievement of tumour-free margins on excision of nonpalpable
      breast lesions that have aroused only an intermediate or low level of suspicion
      before surgery and do turn out to be malignant is a challenge for the surgeon.
      The purpose of this study was to determine factors that influence the probability
      of obtaining tumour-free margins after needle-localised excision of a nonpalpable
      breast carcinoma. METHOD: During a 10-year period all needle-localised breast
      biopsies (NLBB) carried out in the Department of Surgery were retrospectively
      analysed. Possible influential factors considered included: age of the patient,
      year of NLBB, appearance of the lesion on imaging, preoperative diagnostic index,
      method of localisation, surgeon's level of experience, specimen size and
      radiology of the specimen, and all these were analysed in a multivariate logistic
      regression analysis. RESULTS: In all, 400 needle-localised breast biopsies had
      been performed. Excision with tumour-free margins was more often achieved, and
      the final intervention less often took the form of a mastectomy, when the lesion
      was classified preoperatively as malignant (P = 0.02). CONCLUSION: The outcome of
      treatment of a needle-localised breast cancer excision is better when the breast
      lesion is known to be malignant before surgery.

PMID- 15563855
TI  - Vacuum-assisted biopsy device-diagnostic and therapeutic applications in breast
      surgery.
AB  - BACKGROUND: The last three decades have seen a gradual shift in the surgical
      treatment of breast diseases. An example of this is the popularization of minimal
      invasive procedures. The vacuum-assisted biopsy device (VABD) was originally
      introduced as a diagnostic tool; however, improvement in technology (by
      production of larger calibre tools) has now extended the role of VABD to
      therapeutic procedures. DATA SOURCES: An extensive pubmed and medline search was
      conducted from 1990 to 2004, all articles involving the use of VABD were
      retrieved, secondary referencing of suitable articles was also done. CONCLUSION:
      VABD has an expanding role in the surgical treatment of benign breast diseases,
      improvement in technology may further extend its therapeutic role to the excision
      of small malignant lesions. However, the perceived benefits of minimal invasive
      breast surgery need to be validated in randomized controlled studies.

PMID- 15563856
TI  - Skin-sparing mastectomy and immediate breast reconstruction: incidence of
      recurrence in patients with invasive breast cancer.
AB  - The aim of this study was to investigate whether skin-sparing mastectomy (SSM),
      which is gaining increasing importance and gives well-accepted cosmetic results,
      provides adequate treatment of the patients' oncologic disease. From 1995 to
      2003, 60 patients diagnosed with invasive breast cancer were treated with SSM and
      complete axillary dissection. All patients underwent immediate breast
      reconstruction after primary surgery. Patients were treated either with a
      latissimus dorsi flap or with a transversus rectus abdominis myocutaneous flap.
      Depending on the intraoperative analysis of frozen sections, 14 patients were
      treated with preservation of the nipple-areola complex. During a median follow-up
      of 52 months (4-92 months), four local recurrences (6.6%) occurred. One patient
      was also found to have contralateral breast carcinoma. Three patients developed
      distant metastases, and two patients died of their disease a mean of 18 months
      after primary therapy. Factors associated with local recurrence were tumor size,
      poor tumor differentiation, and positive node involvement. SSM followed by
      immediate breast reconstruction is an alternative to modified radical mastectomy
      in a subset of patients with invasive breast cancer. The risk of local recurrence
      is low and is associated with such factors as tumor stage, poor tumor
      differentiation, and node-positive disease. This procedure does not increase the
      risk of distant metastases, which is comparable to that after other surgical
      approaches.

PMID- 15563857
TI  - A decision aid for predicting non-sentinel node involvement in women with breast
      cancer and at least one positive sentinel node.
AB  - BACKGROUND: Several clinical trials are re-evaluating the management of the
      axilla after sentinel node (SN) biopsy. Approximately 50-70% of patients with
      positive SN have no further nodal involvement. Estimates of the risk of non
      sentinel node (NSN) involvement would aid decisions regarding further axillary
      surgery. METHODS: Clinical and pathological variables for 82 breast cancer
      patients with metastasis to at least one SN, were used to find independent
      predictors of the status of NSNs. RESULTS: NSN metastases were found in 46.3% of
      patients. In a regression model patient age, proportion of SN replaced by
      metastasis and number of SNs were independent predictors of NSN status.
      CONCLUSION: Data available after SN biopsy allow estimation of the risk of NSN
      metastases among patients with positive SNs. Individualised estimates of the risk
      of NSN involvement may facilitate discussions regarding the trade off between the
      likely benefits of further axillary surgery and the morbidity of this procedure.

PMID- 15563858
TI  - Wise pattern mastectomy with immediate breast reconstruction.
AB  - A new technique of immediate breast reconstruction is presented. This technique
      uses a silicone implant placed in a subpectoral pocket, using de-epithelialised
      skin from the lower breast to augment the submuscular pocket, thus producing a
      compound myodermal flap. The technique is simple, and the resulting scar is
      cosmetically satisfactory; when combined with reduction mammoplasty on the
      opposite breast, this technique produces satisfactory breast symmetry.

PMID- 15563859
TI  - Glycogen-rich clear cell mammary malignant myoepithelioma.
AB  - Primary clear cell tumors of the breast are uncommon and often present a
      diagnostic challenge. We describe an extremely rare case of glycogen-rich clear
      cell malignant myoepithelioma in a 43-year-old woman. Histologically, this tumor
      is composed of clear cells with abundant cytoplasmic glycogen particles.
      Immunohistochemically, these tumor cells show co-expression of vimentin, smooth
      muscle actin, epithelial membrane antigen, S-100 protein, and cytokeratin as
      evidence of myoepithelial cell tumor. The pathological staging of the patient is
      IIB (pT3N0M0) and the nuclear grading is 2. The patient demonstrated no evidence
      of recurrence or metastasis over a period of 42 months. We suggest that glycogen
      rich clear cell malignant myoepithelioma be included in the histological
      differential diagnosis of clear cell tumors of the breast.

PMID- 15563860
TI  - Imaging of granulomatous mastitis: assessment of three cases.
AB  - Granulomatous mastitis is a benign, inflammatory breast disease of unknown
      aetiology, which can mimic breast carcinoma in its clinical manifestations.
      Imaging features of three cases of granulomatous mastitis mimicking breast
      carcinoma on both clinical and radiographic examination are presented, with
      special emphasis on the role of dynamic contrast-enhanced-magnetic resonance
      mammography in the differential diagnosis.

PMID- 15563861
TI  - Estrogen and combined estrogen-progestogen therapy in the menopause and breast
      cancer.
AB  - Most of the data on menopausal hormone therapy (HT) and breast cancer risk
      available up to the mid-1990s were included in a collaborative reanalysis based
      on over 52,000 women with and 108,000 without breast cancer. HT increased the
      risk of breast cancer by about 2.3% per year of use. Subsequent studies have
      confirmed that breast cancer risk is elevated in current and recent (but not
      past) HT users and that the relative risk (RR) is higher for users of combined
      estrogen-progestin treatment than for users of estrogen only, and this higher RR
      is seen with various types of preparations and different routes of
      administration. With reference to intervention studies, information on combined
      HT derives from the Women's Health Initiative (WHI). After 7 years of follow-up,
      166 breast cancer cases were recorded in the HT group, as against 124 in the
      placebo group, corresponding to a RR of 1.24. Data from two other, smaller,
      randomized studies are available. In a combined analysis of the three randomized
      trials, 205 cases of breast cancer were observed in the treated groups as against
      154 in the placebo groups, corresponding to a pooled RR of 1.27. However, in the
      estrogen-only component of the WHI population, at 8 years of follow-up 94 cases
      were observed in the estrogen group, opposed to 124 in the placebo group
      (RR=0.77). The results recorded in the WHI and the Million Women Study do not
      confirm the suggestion that breast cancers in women using HT have a more
      favorable prognosis. HT has also been related to an increased risk of recurrent
      breast cancer.

PMID- 15563862
TI  - Invasive ductal carcinoma with tissue neutrophilia: a distinct entity?
AB  - Infiltrating ductal carcinoma with tissue neutrophilia in the absence of tumor
      necrosis or clinical evidence of abscess is a rare and unreported phenomenon. A
      case report is described with cytomorphologic features of FNA and histopathology
      with immunohistochemical features.

PMID- 15563863
TI  - Lymphoepithelioma-like carcinoma of the breast: is it a distinct entity?
      Clinicopathological evaluation of two cases and review of the literature.
AB  - Lymphoepithelioma-like carcinomas (LELCs) are tumors with morphologic features
      identical to those of undifferentiated nasopharyngeal carcinoma. They are
      characterized by a pronounced lymphocytic infiltrate, often obscuring the
      neoplastic epithelial component. LELCs have been described in several organs, but
      are extremely rare in the breast. In this report, two cases of LELC of the breast
      are presented with their histological and immunohistochemical features. In situ
      hybridization for Epstein-Barr viral genome was negative in both cases. We
      discuss the differential diagnosis of LELC of the breast and review the reports
      of this entity that have appeared in the literature.

PMID- 15563864
TI  - Management of neuroendocrine differentiated breast carcinoma.
AB  - In neuroendocrine differentiated breast cancer, the coexistence of both
      neuroendocrine and exocrine components may raise some uncertainty about the best
      clinical approach to adopt. We describe the case of a patient with neuroendocrine
      differentiated breast carcinoma with lung metastases, who experienced a partial
      response after epirubicin chemotherapy. During subsequent maintenance hormone
      therapy with letrozole, plasma chromogranin A was consistently elevated even
      though CT showed disease stabilization. The patient was scheduled for surgery and
      radical resection was performed. She is still alive and disease free after over
      37 months. Anthracyclines are effective in the treatment of neuroendocrine
      differentiated breast carcinoma. Surgical resection of metastatic lesions can
      lead to a durable disease-free status. Serial evaluation of circulating
      chromogranin A is useful in the follow-up of these patients.

PMID- 15563865
TI  - Ureteral metastasis of occult breast cancer.
AB  - We report the case of a 59-year-old woman who presented with right flank pain and
      fever. Diagnostic investigations revealed stenosis of the right ureter extending
      over about 1cm. Since a double-J prosthesis could not be passed through it, a
      percutaneous nephrostomy was constructed and surgical exploration and excision of
      the stenotic ureteral segment were then carried out. Histopathological analysis
      of the segment removed showed diffuse infiltration with epithelial tumor cells.
      On immunohistochemistry, these cells were found to be positive for cytokeratin
      and for estrogen and progesterone receptors. No primary cancer and no additional
      metastases were detected. Eleven months later a primary tumor with a metastasis
      in the left supraclavicular region was found in the patient's right breast.

PMID- 15563866
TI  - Breast metastases from cutaneous malignant melanoma.

PMID- 15563867
TI  - Obesity may be a independent prognostic factor in premenopausal breast cancer
      patients.

PMID- 15563868
TI  - Gene mutations in retinitis pigmentosa and their clinical implications.
AB  - Retinitis pigmentosa (RP) is a group of inherited progressive retinal diseases
      affecting about 1 in 3500 people worldwide. So far, there is no prevention or
      cure, with permanent visual loss or even blindness the ultimate consequence
      usually after midlife. The genetics of RP are complex. It can be sporadic,
      autosomal dominant, autosomal recessive, or X-linked. Thirty-two genes are known
      to be associated with RP, sometimes the same gene gets involved in different
      inheritance traits. Some RP cases have a digenic cause. About 60% RP cases still
      have no known genetic cause. A large number of mutations cause RP, and they can
      be deletions, insertions, or substitutions that cause missense mutations or
      truncations. The RHO, RP1, and RPGR genes contribute the greatest number of known
      mutations causative of RP. But there is no single mutation that alone accounts
      for more than 10% of unrelated patients. Genetic testing for RP therefore
      requires screening for a group of genes. High-throughput and automated sequence
      detection technologies are essential. Due to the complexity in phenotype and
      genetics, and the fact that RP is untreatable, genetic testing for presymptomatic
      diagnosis of RP is controversial. Meanwhile, new genes are still to be
      identified, mostly by family linkage and sib-pair analysis. Research on gene
      therapy for RP requires information on gene mutations causative of RP.

PMID- 15563869
TI  - Clinical laboratory differentiation of infectious versus non-infectious systemic
      inflammatory response syndrome.
AB  - OBJECTIVE: To evaluate the accuracy of C-reactive protein (CRP), procalcitonin
      (PCT), neopterin, and endotoxin in the differential diagnosis of sepsis and non
      infectious systemic inflammatory response syndrome (SIRS). METHODS: A Medline
      database and references from identified articles were used to perform a
      literature search relating to the differential diagnosis of sepsis versus non
      infectious SIRS. RESULTS: CRP, PCT, and neopterin are released both in sepsis and
      in non-infectious inflammatory disease. CRP and PCT are equally effective,
      although not perfect, in differentiating between sepsis and non-infectious SIRS.
      However, CRP and PCT have different kinetics and profiles. The kinetics of CRP is
      slower than that of PCT, and CRP levels may not further increase during more
      severe stages of sepsis. On the contrary, PCT rises in proportion to the severity
      of sepsis and reaches its highest levels in septic shock. PCT tends to be higher
      in nonsurvivor than in survivor. Therefore, PCT demonstrated a closer correlation
      with the severity of sepsis and outcome than CRP. Unlike CRP and PCT, neopterin
      is increased in viral infection as well as bacterial infection, and neopterin is
      also a useful indicator of sepsis. Endotoxemia was detected in no more than half
      of patients with Gram-negative bacteremia, and Gram-negative bacteremia was
      detected in half of patients with endotoxemia. CONCLUSIONS: The diagnostic
      capacity of PCT is superior to that of CRP due to the close correlation between
      PCT levels and the severity of sepsis and outcome. Neopterin is very useful in
      the diagnosis of viral infection. The endotoxin assay in combination with CRP,
      PCT, or neopterin may help as a diagnostic marker for Gram-negative bacterial
      infection.

PMID- 15563870
TI  - Drug-induced renal failure: a focus on tubulointerstitial disease.
AB  - Therapeutic agents induce acute renal failure (ARF) by promoting various types of
      injury to the kidney. Acute interstitial nephritis (AIN) develops from
      medications that incite an allergic reaction, leading to interstitial
      inflammation and tubular damage. Acute tubular necrosis (ATN) is a dose-dependent
      process that develops from direct toxicity on tubular epithelia, typically in the
      absence of inflammation. Additional, less common patterns of drug-induced renal
      injury include osmotic nephropathy, crystal nephropathy, and acute
      nephrocalcinosis. This review focuses on the multitude of patterns of drug
      induced renal failure due to tubulointerstitial disease.

PMID- 15563871
TI  - Clinical laboratory advances in the detection of rabies virus.
AB  - Rabies is one of the most feared zoonotic diseases in the world. All warm-blooded
      animals are susceptible to infection by the virus, but the main vectors of human
      infection are dogs and cats. Development of rabies can be prevented by
      postexposure vaccination, and with a few exceptions, the exact time and source of
      human infection is usually known. However, the effective use of postexposure
      vaccination depends on the rapid and accurate detection of rabies virus in
      specimens obtained from the source of human infection. This paper provides an
      overview on developments on laboratory methods for the early detection of rabies
      virus. In most laboratories, the fluorescent antibody test (FAT) is used as the
      most important primary test, with the rabies tissue culture infection test
      (RTCIT) or the mouse inoculation test (MIT) being used as confirmatory backup
      procedures. However, other methods for the detection of antigens, such as rapid
      rabies-specific enzyme-linked immunosorbent assay (rapid-ELISA) and the detection
      of viral nucleic acids by reverse transcription polymerase chain reaction (RT
      PCR) are increasingly being used for diagnosis and, in combination with
      nucleotide sequencing, for epidemiological investigations.

PMID- 15563872
TI  - Development and application of serum cholinesterase activity measurement using
      benzoylthiocholine iodide.
AB  - BACKGROUND: Measurement of cholinesterase activity in serum is important to
      identify substantial liver disease and damage by pesticides, and to assess the
      degree of development of fatty liver and preoperative risk. Many procedures using
      various artificial substrates have been developed but suffer from problems with
      substrate specificity and interference by endogenous substances. METHODS: An
      assay pseudocholinesterase (ChE, EC 3.1.1.8 acylcholine acylhydrolase) activity
      was developed using a stable substrate specific to ChE, benzoylthiocholine iodide
      (BZTC). The thiocholine generated by hydrolysis of BZTC by ChE activity reacts
      with 2, 2'-dipyridildisulfide (2-PDS) to produce 2-thiopyridine (2-TP), which is
      measured at 340 nm. Optimum pH, buffer types and concentrations, substrate
      concentrations, and optimum conditions of the color reaction were investigated.
      The substrate specificity, test interferences, correlation with other measurement
      methods, and reference interval were evaluated. RESULTS: The optimum pH of this
      method was 7.8, and 3-[4-(2-hydroxyethyl)-1-piperazinyl] propanesulfonic acid
      (EPPS) buffer solution was selected. Constant activity was shown at buffer
      concentrations >200 mmol/l, and the maximum activity was shown at a substrate
      concentration of 0.2 mmol/l. When a Hill plot was utilized, the Hill number was
      1.08 and 1.09. The reaction velocity at this substrate concentration was 94% of
      V(max). The K(m) of ChE to BZTC was between 1.2 x 10(-2) and 1.3 x 10(-2) mmol/l.
      The range was 0-300 U/l. The coefficients of variation (CV) for 20 measurements
      of serum containing 53.1, 96.6, and 270.7 U/l of ChE were 0.82%, 0.76%, and
      0.54%, respectively. The relative reactivity of acetylcholinesterase (AChE) to
      this substrate was 2%. The correlation factors of this method to three other
      methods were between 0.993 and 0.998. CONCLUSIONS: This method provides excellent
      specificity, reproducibility, a wide measurement range, and minimal interference
      from endogenous substances to common serum analytes. Correlation of this method
      with conventional methods was good. Because the reagents are stable after
      preparation, this assay is useful for routine analysis.

PMID- 15563873
TI  - Urinary insulin-like growth factor-I measurement in an actual sport competition,
      an additional approach in laboratory antidoping tests.
AB  - BACKGROUND: The insulin-like growth factor hormone (IGF-I) is an important
      protein hormone under investigation with physical exercise and for doping
      detection. Urinary IGF-I level in fact represents a relevant measurement when the
      postexercise proteinuria is under analysis. To verify the IGF-I level variation
      in the circulation and in urinary excretion in the occasion of a competition, the
      plasma and urine IGF-I in athletes before and after an actual competitive event
      were measured. METHODS: Twenty well-trained cyclists took part in a competition
      (102 km) and concluded the intense physical exercise in approximately 2(1/2) h.
      Urine and blood samples were collected from each athlete 10-20 min before and at
      the end of the competition. Plasma and urine total IGF-I (pIGF, uIGF), total
      urinary proteins (uPr), and creatinine (uCr) concentrations were measured.
      RESULTS: The uIGF [from 76.2+/-15.8 to 256.9+/-29.1 ng/l (p<0.001)], uPr [from
      29.4+/-6.7 to 325.9+/-95.1 mg/l (p<0.005)], and uCr [from 6.3+/-1.0 to 10.0+/-0.8
      mmol/l (p<0.005)] significantly increased. The pIGF was 262.6+/-14.3 and 247.3+/
      11.8 microg/l before and end-exercise, respectively. A statistical correlation
      between uIGF and uPr was demonstrated (p<0.001). The pIGF/uIGF ratio was
      significantly (p<0.05) decreased comparing the end with before the competition.
      CONCLUSIONS: The pIGF/uIGF significantly decreased at the end, compared with
      before the competition, suggesting a changed uIGF excretion. This increment
      appeared to be increased, although not significantly, considering the ratio with
      uCr.

PMID- 15563874
TI  - Differential expression of carbonic anhydrase isoenzymes in various types of
      anemia.
AB  - BACKGROUND: The aim of the present study was to determine the concentrations of
      cytosolic carbonic anhydrase (CA) isoenzymes in erythrocytes of patients with
      aplastic, autoimmune hemolytic, iron deficiency or beta-thalassemia anemia.
      METHODS: Western blotting and CA esterase activity analysis were used to analyze
      cytosolic erythrocyte CA isoenzymes in 118 subjects with various types of anemia
      and 35 healthy controls. RESULTS: Total CA activity and CAII concentration of
      anemia patients were significantly higher than that of the control subjects while
      CAI concentration was significantly lower in patients of autoimmune hemolytic
      anemia (P<0.01). Compared with controls, CAIII concentration was lower in iron
      deficiency anemia (P<0.01), but higher in beta-thalassemia anemia (P<0.001).
      CONCLUSIONS: Carbonic anhydrase isoenzymes may contribute differently to various
      types of anemia. CAI may be an indicator to differentiate autoimmune hemolytic
      anemia from other types of anemia. CAII provides the CA activity necessary for
      maintaining ion transport in erythrocytes while CAIII may play an agent against
      oxidative damage in iron deficiency and beta-thalassemia anemia.

PMID- 15563875
TI  - Association between the eNOS (Glu298Asp) and the RAS genes polymorphisms and
      premature coronary artery disease in a Turkish population.
AB  - BACKGROUND: The renin-angiotensin system (RAS) and endothelial nitric oxide (NO)
      affect the pathogenesis of atherosclerosis and prognosis of coronary artery
      disease (CAD). Previous epidemiologic data suggested that genetic factors are
      more likely to affect young rather than old people. Our objective was to
      investigate the association between the polymorphisms of eNOS (Glu298Asp) and the
      RAS genes and premature CAD in a Turkish population. METHODS: A total of 115
      Turkish patients with premature CAD and 83 controls were included in the study.
      ACE I/D, AT1R A/C, AGT T/M and eNOS Glu298Asp gene polymorphisms were analysed by
      polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP). RESULTS: It was found that increased premature CAD risk is associated
      with higher frequencies of the ACE DD [OR: 2.600 (CI 95% 1.395-4.847, p=0.002)],
      AGT MM [OR=2.407 (CI 95% 1.267-4.573, p=0.007)] and eNOS 894TT [OR=17.000 (CI 95%
      3.952-73.125, p<0.001)] genotypes. Carriers of ACE DD+eNOS 894TT (p=0.002), AGT
      MM+eNOS 894TT (p=0.001), AT1R AA+eNOS 894TT and AT1R non-AA+eNOS 894TT (p=0.002)
      genotypes were significantly associated with the risk of premature CAD.
      CONCLUSIONS: This study indicates a synergistic contribution of RAS genes (ACE
      I/D, AGT T/M, AT1R T/C) and eNOS Glu298Asp polymorphisms to the development of
      the premature CAD.

PMID- 15563876
TI  - Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3,
      conducting the cardiac fast transient outward current (ITO,f), are not a frequent
      cause of long QT syndrome.
AB  - BACKGROUND: Long QT syndrome (LQTS) is a hereditary cardiac arrhythmogenic
      disorder characterized by prolongation of the QT interval in the
      electrocardiogram, torsades de pointes arrhythmia, and syncopes and sudden death.
      LQTS is caused by mutations in ion channel genes. However, only in half of the
      families is it possible to identify mutations in one of the seven known LQTS
      genes, why further genetic heterogeneity is expected. The genes KCND2 and KCND3,
      encoding the alpha-subunits of the voltage-gated potassium channels Kv4.2 and
      Kv4.3 conducting the fast transient outward current (I(TO,f)) of the cardiac
      action potential (AP) in the myocardium, have been associated with prolongation
      of AP duration and QT prolongation in murine models. METHODS: KCND2 and KCND3
      were examined for mutations using single-strand conformation polymorphism (SSCP)
      analysis in 43 unrelated LQTS patients, where mutations in the coding regions of
      known LQTS genes had been excluded. RESULTS: Seven single nucleotide
      polymorphismsm (SNPs) were found, two exonic SNPs in KCND2 and three exonic and
      two intronic in KCND3. None of the five exonic SNPs had coding effect. All seven
      SNPs are considered normal variants. CONCLUSION: The data suggest that mutations
      in KCND2 and KCND3 are not a frequent cause of long QT syndrome.

PMID- 15563877
TI  - Effect of alpha-tocopherol supplementation on blood pressure and lipidic profile
      in streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats.
AB  - INTRODUCTION: Antioxidants has been utilized to prevent oxidative damage in
      diabetes and hypertensive diseases. The current study evaluated the effect of
      alpha-tocopherol supplementation on blood pressure and the lipid profile in
      streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats
      (SHR). METHODS: The systolic blood pressure and total cholesterol, LDL
      cholesterol, HDL-cholesterol and triglycerides were measured in SHR-diabetes
      induced. RESULTS: Treatment with alpha-tocopherol (vitamin E) led to a decrease
      on systolic blood pressure and showed an increase of HDL-cholesterol and a
      decrease of LDL-cholesterol, but the concentrations of triglycerides and total
      cholesterol were not changed. CONCLUSIONS: The vitamin E was able to modulate the
      blood pressure and the lipidic profile as well, and therefore can be considered
      as an alternative treatment of lipid disorder found on diabetes and hypertension
      diseases.

PMID- 15563878
TI  - Effect of N-benzoyl-D-phenylalanine and metformin on carbohydrate metabolic
      enzymes in neonatal streptozotocin diabetic rats.
AB  - BACKGROUND: The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin was
      studied on the activities of carbohydrate metabolic enzymes in neonatal
      streptozotocin (nSTZ) non-insulin-dependent diabetic rats. METHODS: To induce non
      insulin-dependent diabetes mellitus (NIDDM), single dose injection of
      streptozotocin (STZ; 100 mg/kg body weight; i.p.) was given to 2-day old rats.
      After 10-12 weeks, rats weighing >150 g were selected for screening in NIDDM
      model, they were checked for fasting blood glucose concentrations to conform the
      status of NIDDM. NBDP (50,100 and 200 mg/kg body weight) was administered orally
      for 6 weeks into the confirmed diabetic rats. RESULTS: The activities of
      gluconeogenic enzymes were significantly increased, whereas the activities of
      hexokinase and glucose-6-phosphate dehydrogenase were significantly decreased in
      nSTZ diabetic rats. Both NBDP and metformin were able to restore the altered
      enzyme activities to almost control concentrations. Combination treatment was
      more effective than either drug alone. CONCLUSION: The administration of NBDP
      along with metformin to nSTZ diabetic rats normalizes blood glucose and causes
      marked improvement of altered carbohydrate metabolic enzymes during diabetes.

PMID- 15563879
TI  - Determination of apolipoprotein B-48 in serum by a sandwich ELISA.
AB  - BACKGROUND: Apolipoprotein B-48 (apoB-48) is produced by the small intestine, as
      a part of chylomicrons (CMs), and appears to be a suitable marker for clinical
      studies of postprandial lipoproteins and related cardiovascular risk factors. We
      have developed an assay for routine analysis to quantify apoB-48 in serum or
      plasma. METHODS: A microtiter plate was coated with monoclonal antibody (4C8)
      raised against apoB-48 C-terminal specific decapeptide. Serum samples were
      diluted 100-fold with 0.05 mol/l Tris-HCl buffer (with or without 0.1% Triton X
      100). Appropriate calibration curves were obtained in the ELISA by using apoB-48
      recombinant antigen. RESULTS: No cross-reactivity (<0.001%) was found with apoB
      100, as verified by ELISA and Western blot analyses. Intra- and inter-assay CVs
      were 4.8% and 5.4%, respectively. Recovery of added recombinant apoB-48 in serum
      was within 94-105%. The assay linearity was intact >5-fold dilution of serum by
      dilution buffer. ApoB-48 levels in healthy controls (n=18) at fasting were within
      the range of 2.69-6.56 microg/ml (mean+/-S.D.: 4.60+/-1.54 microg/ml). In healthy
      subjects, serum apoB-48 concentrations markedly increased in the postprandial
      state, in parallel with serum triglycerides. CONCLUSION: This method for
      measuring apoB-48 using the monoclonal antibody 4C8 is simple, reliable and
      suitable for routine analyses.

PMID- 15563880
TI  - Discrepancy between sperm acrosin activity and sperm morphology: significance for
      fertilization in vitro.
AB  - BACKGROUND: In routine semen analysis, discrepancies may occur between sperm
      acrosin activity test results and sperm acrosomal morphology. METHODS: Discrepant
      test results of sperm acrosin activity (spectrophotometric assay) vs. sperm
      morphology (strict criteria) in the initial diagnostic investigation of 107
      infertile couples were evaluated with respect to fertilization rate (% oocytes
      with 2 pronuclei) further obtained in IVF treatment. RESULTS: Acrosin activity
      positively correlated with sperm morphology (% normal forms) (r=0.537) and
      fertilization rate (r=0.526). ROC curves for the prediction of > or =50%
      fertilization rate were comparable for acrosin activity and sperm morphology,
      with optimal cutoff values at 25 microIU/10(6) sperm and 10%, respectively. In
      multiple regression analysis, sperm acrosin activity (P=0.002) predicted
      fertilization rate independently of sperm morphology (P<0.001) and sperm vitality
      (eosin-nigrosin stain) (P=0.03). Acrosin activities > or =25 microIU/10(6) sperm
      were observed in 36% of severe teratozoospermic samples (< or =4% normal
      spermatozoa) associated with low fertilization rate. Twenty percent of the
      morphologically normal ejaculates showed a low acrosin activity (<25
      microIU/10(6) sperm) and low hypoosmotic swelling test (HOST) scores (31.4+/
      7.6%) and were associated with low fertilization rate. CONCLUSION: The sperm
      acrosin assay can help to predict sperm fertilizing capacity in IVF independently
      of sperm morphology.

PMID- 15563881
TI  - Characteristics and performance of an immunosorbent assay for human matrix Gla
      protein.
AB  - BACKGROUND: Matrix gammacarboxyglutamate (Gla)-protein (MGP) is a strong
      inhibitor of soft tissue calcification and is mainly produced by chondrocytes and
      vascular smooth muscle cells (VSMCs). MGP-deficient mice have extensive
      calcifications of cartilage and arteries leading to osteopenia, fractures and
      blood vessel ruptures. Promotor polymorphisms resulting in decreased expression
      levels were found to be associated with an increased risk for cardiovascular
      disease in humans. METHODS: Recently, an ELISA-based assay has become available
      with which MGP may be detected in the circulation. The principle of the test kit
      is that of a competitive immunoassay using a monoclonal antibody against MGP
      bound to the microtiter plate. RESULTS: Here, we report on a critical evaluation
      of this assay and its potential diagnostic utility in diseases associated with
      the degeneration of the arterial vessel wall and cartilage. The biochemical
      performance of the kit is satisfactory, and significant differences were found
      between a number of patient cohorts and the reference population. Serum MGP
      concentrations were significantly decreased in patients with angina pectoris and
      in various cartilage diseases. CONCLUSIONS: The assay allows comparison of groups
      and may become a suitable marker for risk assessment or diagnosis in
      cardiovascular disease and osteoarthritis.

PMID- 15563882
TI  - Rapid analysis of total plasma homocysteine by tandem mass spectrometry.
AB  - Elevated plasma homocysteine levels may be an independent risk factor for
      premature vascular disease. Early detection and population screening are
      warranted to recognise hyperhomocysteinemia and initiate homocysteine lowering
      therapy. Current methods for homocysteine analysis are time consuming, labor
      intensive and/or expensive. We developed a sensitive and fast method for
      homocysteine analysis based on tandem mass spectrometry that avoids the need for
      derivatization and preanalytical chromatography.

PMID- 15563883
TI  - S100B and NSE serum concentrations in Machado Joseph disease.
AB  - BACKGROUND: NSE and S100B are considered as neuronal and glial peripheral markers
      of central nervous system pathologies, respectively. We evaluated the potential
      use of S100B and NSE serum concentrations as peripheral markers of symptomatic
      patients with Machado Joseph disease (MJD). METHODS: We measured S100B and NSE
      peripheral concentrations of 22 MJD patients and compared with healthy subjects
      concentrations. The correlations of both markers with CAG repeat size, age of
      onset, disease duration, and the scores of the Extended Disability Status Scale
      of Kurtzke, Unified Parkinson's Disease Rating Scale, and the Montgomery-Asberg
      depression rating scale were also assessed. RESULTS: S100B serum concentrations
      between control and MJD subjects were not statistically different, whereas NSE
      serum concentrations were higher in MJD patients than in control subjects
      (p=0.00001). S100B presented a moderate correlation with disease duration and
      depression score, whereas NSE presented a moderate correlation with depression
      score and a good negative correlation with EDSS score. CONCLUSIONS: Symptomatic
      MJD patients present increased concentrations of NSE and normal concentrations of
      S100B in blood.

PMID- 15563884
TI  - Diagnosis of suspected trimethylaminuria by NMR spectroscopy.
AB  - BACKGROUND: Trimethylamine (TMA) is a volatile substance produced in the gut,
      absorbed into the blood and further metabolized by healthy individuals into
      trimethylamine-N-oxide (TMAO) by TMA-oxidase and then excreted in urine. Patients
      suffering from trimethylaminuria (TMAU) show an impaired enzymatic oxidation of
      TMA, excreting this amine in breath, urine and other body secretions which
      confers an unpleasant body odor. METHODS: We diagnosed a Brazilian adult male
      patient suspected of trimethylaminuria with a burden of choline bitartarate by
      monitoring the urinary excretion of TMA and TMAO by proton nuclear magnetic
      resonance spectroscopy ((1)H-NMR). RESULTS: The patient's urinalyses showed an
      augmented TMA (12.64+/-0.95 mg/l) and TMAO (88.42+/-0.82 mg/l) excretion 6 h
      after the overload test representing an oxidation capacity of 84.6%, consistent
      with a heterozygosis condition. Diets containing tuna fish or eggs resulted in an
      excretion of TMA and TMAO similar to that of the control diet. Only the diet
      based on dogfish, rich in TMAO, enhanced the excretion of TMA and TMAO reaching
      24.65 and 1055.55 mg/l, respectively, in the 0-24 h urine sample. CONCLUSIONS: It
      was concluded first, that the patient was not able to metabolize the dietary
      overload of TMA and second, that more studies are needed to substantiate foods
      that should be avoided, especially regarding fish, due to their high TMA
      precursor contents.

PMID- 15563885
TI  - Novel mutations in the BCHE gene in patients with no butyrylcholinesterase
      activity.
AB  - BACKGROUND: Butyrylcholinesterase (BCHE) deficiency is characterized by prolonged
      apnea after the use of certain muscle relaxants with the genetic defect lying in
      the BCHE gene. METHODS: Two Chinese patients with no serum BCHE activity were
      studied. The BCHE genes were screened for mutations by polymerase chain reaction
      and direct DNA sequencing. RESULTS: Of the four mutations detected, two novel
      mutations were identified in the two patients, i.e., F474L, and an insertion of
      an adenine between nucleotide positions 395 and 396. This information was used to
      screen the immediate families of the patients for carrier status. CONCLUSIONS: We
      established the molecular basis of butyrylcholinesterase deficiency in two
      Chinese patients. The developed mutation detection assay provides a reliable
      method for identifying mutant BCHE carriers.

PMID- 15563886
TI  - Relationship of serum leptin with age, body weight, body mass index, and bone
      mineral density in healthy mainland Chinese women.
AB  - BACKGROUND: Serum leptin concentration is associated with age, fat and bone
      mineral density (BMD), and there are ethnic differences in physique and BMD
      values. The relationship between serum leptin concentration and BMD in Chinese
      women is presently unknown. We examined the relationship of serum leptin
      concentration with age, body weight, BMI and BMD in mainland Chinese women.
      METHODS: Serum leptin concentration in a population of 676 Chinese females, aged
      20-80 years (45.4+/-14.8 years, mean+/-S.D.), was measured using an enzyme-linked
      immunosorbent assay (ELISA). BMD values were measured by dual-energy X-ray
      absorptiometry (DXA) at a number of sites: the posteroanterior lumbar spine (PA,
      L1-L4), lateral lumbar spine (Lat, L2-L4), hip (including the femoral neck (FN)
      and total hip (T-hip)), and forearm (one-third region (RU1/3) and total region
      (RUT)). The relationship between changes in serum leptin concentration with age,
      body weight, height, body mass index (BMI) and BMD values at six sites were
      analyzed using 10 different regression models, and the models giving the best fit
      were selected. RESULTS: The cubic regression model best described the changes in
      serum leptin concentration with age (R(2)=0.048, p<0.001) and body weight
      (R(2)=0.352, p<0.001), while the quadratic regression model was best for serum
      leptin concentration changes with BMI (R(2)=0.410, p<0.001); serum leptin
      concentration was not correlated with height. Serum leptin concentration was
      significantly higher in postmenopausal than premenopausal women (p<0.001). Serum
      leptin concentration was correlated with Lat BMD (R(2)=0.012, p<0.018), FN BMD
      (R(2)=0.006, p<0.041) and T-hip BMD (R(2)=0.013, p<0.004) in the whole
      population. In premenopausal women, leptin was positively associated with BMD
      except for Lat (R(2)=0.029-0.055, p<0.008); in postmenopausal women, leptin was
      also positively associated with AP, FN, T-hip BMD (R(2)=0.026-0.042, p<0.007).
      However, after adjusting for BMI not for body weight, there was no association
      between serum leptin concentration and age. Meanwhile, after adjustment for age,
      body weight and BMI, there was no association between serum leptin concentration
      and BMD values in premenopausal and postmenopausal women. CONCLUSIONS: Age
      related changes in serum leptin concentration is dependent on BMI, but not a
      direct determinant of BMD in Chinese females.

PMID- 15563887
TI  - Rapid, accurate and non-invasive detection of cerebrospinal fluid leakage using
      combined determination of beta-trace protein in secretion and serum.
AB  - BACKGROUND: beta-Trace protein (Btp) has been proposed as a valuable marker of
      cerebrospinal fluid (CSF) leakage overcoming the drawbacks of beta-2-transferrin
      (B-2Tr) determination. However, there is still controversy about the appropriate
      cut-offs to be used (range 0.35-6 mg/L). The aim of the study was to evaluate cut
      offs of Btp determination for detection CSF leakage. Further, we assessed whether
      the Btp secretion to serum ratio (Btp-sec/ser-ratio) would add diagnostic value.
      METHODS: Prospective study in patients with suspected CSF leakage. Quantitative
      determination of Btp in secretion and serum (Dade-Behring) and qualitative
      measurement of B-2-Tr in secretion and serum. Results were assessed in view of
      clinical data. Cut-offs and diagnostic characteristics were determined by ROC
      analysis. RESULTS: A total of 176 samples were assessed originating from 105
      patients. In 43 samples CSF leakage could be confirmed. Sensitivity of B-2-Tr was
      84%, specificity amounted to 100%. The area under the curve (AUC) for Btp
      measurement in secretion was 0.98. At a cut-off of 0.68 mg/L, sensitivity was
      100% and specificity 91%. At a cut-off of 1.11 mg/L, the specificity was 100%
      with a sensitivity of 93%. The Btp-sec/ser-ratio has an AUC of 0.99. Combining a
      0.68 mg/L cut-off in secretion with a Btp-sec/ser-ratio cut-off of 4.9 reveals a
      sensitivity of 99% and a specificity of 100%. CONCLUSIONS: Btp is a rapid and
      accurate marker for the presence of CSF leakage. Combining measurement of Btp in
      secretion together with determination of the Btp-sec/ser-ratio enhances the
      diagnostic characteristics of the Btp assay. Determination of Btp in both serum
      and secretion is thus recommended.

PMID- 15563888
TI  - Preeclampsia-associated reduction of cathepsin D activity in the umbilical cord.
AB  - BACKGROUND: Preeclampsia is accompanied by an increase of collagen contents in
      the umbilical cord (UC) arteries and in Wharton's jelly. Cathepsin D is one of
      the enzymes which participates in collagen degradation and activates precursor
      forms of collagenolytic metalloproteinases. It was decided to evaluate the
      activity of cathepsin D within umbilical cord arteries, veins and Wharton's jelly
      and its alterations in preeclampsia. MATERIALS AND METHODS: Umbilical cord
      components were separated and submitted to homogenisation/extraction with 0.05 M
      Tris-HCl+0.2% Triton X-100, pH 7.5. Proteolytic activities of the extracts were
      studied with a use of cathepsin D-specific substrate. Western immunoblot
      technique was employed to detect this enzyme. RESULTS: It was found that human
      umbilical cord tissues contain both active and inactive forms of cathepsin D.
      Preeclampsia is associated with a distinct increase in the amount of this enzyme
      in the umbilical cord, whereas its activity deeply decreased. Activation with
      trypsin augments cathepsin D activity in preeclamptic umbilical cord to the
      values observed in control arteries or even exceeds the control values (veins,
      Wharton's jelly). CONCLUSIONS: Preeclampsia is associated with a reduction in the
      activity of cathepsin D in human umbilical cord. The low activity of cathepsin D
      may reduce collagen degradation and enhance its accumulation in the umbilical
      cord, especially in the arteries. Similar changes in other foetal blood vessels
      may result in an increase of vascular resistance and hypertension, which may
      persist after birth.

PMID- 15563889
TI  - Chlorella dichloromethane extract ameliorates NO production and iNOS expression
      through the down-regulation of NF kappa B activity mediated by suppressed
      oxidative stress in RAW 264.7 macrophages.
AB  - BACKGROUND: It has been proposed that chlorella extracts have antioxidative and
      anti-inflammatory effects. METHODS: RAW 264.7 murine macrophage cell line was
      preincubated with various concentrations (0-100 mug/ml) of chlorella
      dichloromethane extract (CDE) and stimulated with lipopolysaccharide (LPS) to
      induce oxidative stress and inflammation. RESULTS: Treatments of CDE reduced
      thiobarbituric acid-reactive substances (TBARS) accumulation, enhancing
      glutathione level and activities of antioxidative enzymes including superoxide
      dismutase (SOD), catalase, glutathione peroxidase (GSH-px), and glutathione
      reductase in LPS-stimulated macrophages than LPS-only treated cells. Nitric oxide
      (NO) production was significantly suppressed in a dose-dependent manner (p<0.05)
      with an IC(50) of 30.5 microg/ml. Treatment of CDE at 50 microg/ml suppressed NO
      production to 6% of LPS-control. Treatment with CDE suppressed the levels of
      inducible nitric oxide synthase (iNOS) protein and mRNA expressions. The specific
      DNA binding activities of nuclear factor kappa B (NF kappa B) on nuclear extracts
      from CDE treatments were significantly suppressed with an IC(50) of 62.7 mug/ml
      in a dose-dependent manner. CONCLUSIONS: CDE ameliorates NO production and iNOS
      expression through the down-regulation of NF kappa B activity, which may be
      mediated by attenuated oxidative stress in RAW 264.7 macrophages.

PMID- 15563890
TI  - Comparison of oxidative damage in Malaysian end-stage renal disease patients with
      or without non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Comparisons of oxidative indices and total antioxidant status between
      end-stage renal disease (ESRD) patients with or without diabetes is scant,
      especially in the Asian population. METHOD: The assays were carried out according
      to known established protocols. RESULT: The present study showed that ESRD
      patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not
      have any significant differences in antioxidant enzyme activities, advanced
      glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric
      reducing ability of plasma (FRAP), indicating that hyperglycemia does not
      exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione
      peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD
      groups (with and without NIDDM). The dialysis process did not alter the
      antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP
      levels. CONCLUSION: Oxidative stress is present in ESRD but this is not
      significantly exacerbated by hyperglycemia. The contribution of components in the
      pathology of renal failure towards oxidative stress exceeds that of
      hyperglycemia.

PMID- 15563891
TI  - The relationship of APOE genetic polymorphism with susceptibility to multiple
      sclerosis and its clinical phenotypes in Kuwaiti Arab subjects.
AB  - BACKGROUND: The possible pathogenetic relationship between APOE genetic
      polymorphism and susceptibility to a variety of neurodegenerative disorders,
      including multiple sclerosis, is controversial. Previous studies have been
      conducted in Caucasian subjects, with little or no data on subjects from the
      Arabian Gulf. We compared the frequencies of specific APOE genotypes and alleles
      in patients with multiple sclerosis (MS) with frequencies observed in a healthy
      control Kuwaiti Arab population to relate APOE frequencies with specific
      identifiable clinical features of the disease. METHODS: Two groups of subjects
      were studied: (i) 39 (17 M, 22 F) patients with clinical evidence of MS; (ii) 106
      apparently healthy Kuwaitis recruited as control subjects. The MS patients had
      detailed clinical and laboratory evaluations, and APOE genotypes were determined
      in all the subjects (patients and controls) by validated PCR methods. Differences
      in frequencies of APOE alleles and associations of specific alleles with clinical
      features were assessed. RESULTS: There were no significant differences in allele
      frequencies between patients and controls, although there was a statistically
      insignificant trend towards lower APOE2 allele frequency in the patients
      (p=0.09). There was a significant association of the APOE4 allele with female
      gender in the patients (p<0.05). CONCLUSION: In Kuwaitis, a population with low
      MS prevalence, no statistically significant associations between APOE genetic
      polymorphism and susceptibility to MS could be established, but there was a trend
      towards a lower APOE2 frequency with MS and towards increased frequency of APOE4
      in female patients and with severe disease.

PMID- 15563892
TI  - Mutations profile in Chinese patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: There are more than 1 million patients with hypertrophic
      cardiomyopathy (HCM) in China, but the genetic basis is presently unknown.
      METHODS: We investigated 100 independent patients with HCM (proband 51, sporadic
      49) by sequencing the three most frequent HCM-causing genes (MYH7, MYBPC3,
      TNNT2). RESULTS: Thirty-four patients (34%) carried 25 types of mutations in the
      selected genes, most (14/25) were newly identified. MYH7 and MYBPC3 accounted for
      41% and 18% of the familial HCM, respectively. TNNT2 mutations only caused 2% of
      the familial HCM. These results suggested that MYH7 and MYBPC3 were the
      predominant genes responsible for HCM, and TNNT2 mutation less proportionally
      contributed to Chinese HCM. MYH7 mutations caused HCM at younger age, more
      frequent syncope and ECG abnormalities compared with MYBPC3 mutations. The
      patients carrying R663C, Q734P, E930K in MYH7 and R130C in TNNT2 expressed
      malignant phenotype. R403Q in MYH7, the most common hot and malignant mutation in
      Caucasians, was not identified in Chinese. CONCLUSION: We confirmed the diversity
      of mutation profile in different populations and suggest that a global registry
      of HCM mutations and their phenotypes is necessary to correlate genotype with
      phenotype.

PMID- 15563893
TI  - Analytical and biochemical aspects associated with supraphysiological creatine
      intake.

PMID- 15563905
TI  - Basic anatomy and physiology of olfaction and taste.
AB  - The chemical senses of taste and smell are important to survival and quality of
      life. Both senses rely on the binding of odorant molecules to receptors located
      on the receptor cells. Olfaction and gustation have complex systems of coding,
      but they display differing methods for coding the receptor stimulus. Both have
      numerous central projections that allow for the perception and interpretation of
      these important sensory inputs.

PMID- 15563906
TI  - Clinical assessment of patients with smell and taste disorders.
AB  - Clinical assessment of the patient who has smell and taste disorders requires
      understanding of the etiology of the olfactory and gustatory disorders. Available
      clinical tests of olfactory and gustatory systems allow detecting and measuring
      the degree of the sensory loss, but are unable to determine the cause and give
      neither prognostic information nor therapeutic guidance. With physical
      examination, however, clinical history can help to establish the diagnosis and
      guide the treatment if available. A clinician evaluating a patient who has smell
      and taste loss must understand that "taste" complaints usually are symptoms of an
      olfactory dysfunction. The distinction between true gustatory loss (bitter,
      sweet, salty, sour, or umami) and olfactory loss, the inability to perceive
      complex flavors of food, will help clarify the patient's diagnosis. Easy-to
      administer tests are available for olfactory (eg, UPSIT) and gustatory testing
      (eg, spatial tests, taste sticks, tasting tablets). In rare circumstances,
      imaging studies (eg, MRI, CT) are indicated.

PMID- 15563907
TI  - Chronic sinusitis and olfactory dysfunction.
AB  - Chronic rhinosinusitis encompasses a group of disorders characterized by
      inflammation of the mucosa of the nose and paranasal sinuses of at least 12
      weeks' duration. In addition to nasal obstruction and discharge, chronic
      sinusitis is a common cause of olfactory dysfunction. Smell loss can result in
      problems including safety concerns, hygiene matters, appetite disorders, and
      changes in emotional and sexual behavior. Although smell loss related to
      sinonasal disease is probably the most treatable form of olfactory dysfunction
      and treatment can improve olfactory sensation in the setting of sinusitis, most
      studies show that the effects are usually transient and incomplete.

PMID- 15563908
TI  - Postviral olfactory loss.
AB  - A viral upper respiratory infection is one of the most commonly identified causes
      of olfactory loss, accounting for 20% to 30% of patients in most series. Given
      the ubiquitous nature of upper respiratory infections, it is not clear what
      predisposes some patients to develop this complication. Studies have demonstrated
      degenerative changes within the olfactory epithelium, the severity of which seems
      to correlate with the severity of olfactory loss. Although no available therapy
      has proved effective, long-term follow-up data have found that approximately two
      thirds of these patients eventually experience a significant improvement in their
      olfactory function.

PMID- 15563909
TI  - Effects of head injury on olfaction and taste.
AB  - Traumatic events such as motor vehicle accidents, falls, or assaults can lead to
      dysfunction in olfaction or gustation. Mechanisms of posttraumatic olfactory
      dysfunction include direct injury to the sinonasal tract or olfactory epithelium,
      shearing effect on olfactory fibers at the cribriform plate, or brain contusion
      or intraparenchymal hemorrhage. Posttraumatic gustatory dysfunction is rare, but
      may occur as a result of direct injury to the tongue, injury to cranial nerves
      VII or IX, or brain contusion or hemorrhage. Evaluation of head-injured patients
      presenting with olfactory or gustatory complaints should include a thorough
      history, including assessment for pre-and posttraumatic chemosensory dysfunction
      and potential mechanisms of injury, complete head and neck examination including
      nasal endoscopy and cranial nerve testing, and focused radiographic imaging,
      usually CT of the sinuses and skull base. Formal olfactory and gustatory testing
      may be performed using various techniques, although in cases potentially
      involving litigation, methodologies able to detect malingering should be used.
      Treatable causes of chemosensory disturbance, most notably conductive olfactory
      losses caused by chronic rhinosinusitis or nasal obstruction, should be ruled
      out. In the event of neurosensory deficits, recovery may occur up to 12 to 18
      months after the traumatic event. All patients should be counseled regarding the
      risks of their chemosensory deficits, and given suggestions for appropriate
      compensatory strategies.

PMID- 15563910
TI  - Olfactory loss as a result of toxic exposure.
AB  - Olfactory loss can occur through accidental exposure, poor industrial hygiene, or
      exposure to low levels of toxins in the ambient air over long periods. This loss
      can lead to transient olfactory disorders, irreversible anosmia, temporary
      olfactory fatigue, or industrial anosmia. Inevitably, a practicing
      otolaryngologist will encounter a patient with complaints of decreased smell and
      taste that initially may be difficult to diagnose and treat. Much of the
      challenge in evaluating a patient with disturbances of olfaction is in obtaining
      adequate quantitative measurements of sensory dysfunction and identifying a
      source for the olfactory loss. Although there is no particular test for
      environmental toxins as a source of olfactory loss, an accurate cause can be
      determined by obtaining a careful, detailed history. A significant exposure
      history and lack of more common causes of olfactory loss strengthens an argument
      for environmental toxins as an etiology. Unfortunately, no available treatments
      can reverse permanent damage caused by toxic exposure, but removal from the
      source of toxins may allow for repair of the olfactory system and return of
      normal function, especially in acute exposures. Despite the increasing number of
      studies investigating toxic exposure on olfactory function, these effects are
      understood poorly. With continued study of human exposure to these substances and
      the use of animal models, the mechanisms by which damage occurs will be
      understood better and new approaches for diagnosis and treatment will be
      developed. Furthermore, with increasing regulations of occupational environments
      and stricter policies on industrial air pollution, olfactory dysfunction
      secondary to toxicity should become less prevalent.

PMID- 15563911
TI  - Aging and olfactory and taste function.
AB  - This article focuses on the change in olfaction and taste with aging. It
      discusses histopathology with an emphasis on age-related changes, causes of
      chemosensory dysfunction in the elderly, how to evaluate a patient with
      dysfunction, useful tests and imaging, clinical consequences of chemosensory
      impairments, and available treatment options.

PMID- 15563912
TI  - Effects of drugs on olfaction and taste.
AB  - The fact that so many varied medications reportedly affect taste and smell is a
      testament to the complexity of the gustatory and olfactory systems. The
      reception, transduction, propagation, and perception of a chemical tastant or
      odorant requires the effective operation of numerous mechanisms--all of which may
      be susceptible in one way or another to a prescribed medication. Just as a
      diuretic may block the apical ion channels on a taste bud, or an antifungal can
      inhibit cytochrome p450-dependent enzymes at the level of the receptors, a
      chemotherapeutic agent can destroy mitosis in a replicating receptor cell and a
      steroid can lead to candidal overgrowth on the tongue surface. Medications not
      only have a perceivable taste themselves at times, but they can alter the
      mechanisms responsible for the ultimate perception of tastes and smells--either
      by direct or secondary means. It should be emphasized, as noted earlier in this
      article, that while many medications are to blame for the impairment or
      distortion of the gustatory or olfactory systems, it is not uncommon that the
      underlying medical problem for which they are prescribed is actually the culprit.
      Examples include epilepsy, migraines, hypothyroidism, schizophrenia, infections,
      and cancer. In fact, simple partial seizures emanating from regions of the brain
      such as the amygdala, hippocampus, parietal operculum, and rolandic operculum can
      lead to the chemosensory sensations that are most commonly considered unpleasant,
      such as "rotten apples," "cigarette," "peculiar," or "vomitus". While removing or
      changing an offending medication can reverse the effects on smell or taste
      perception, it is important to remember that lasting impairment may occur. This
      is vital for a physician to recognize prior to prescribing a medication. It is
      also necessary to report this to patients who may be devastated by chemosensory
      alterations after starting a new medication (eg, pastry chef, perfumist, wine
      specialist, plumber). Among the "risks" in a risks/benefits discussion with a
      patient regarding the use of a new medication, alterations in olfaction and taste
      appear to play an increasingly recognized role.

PMID- 15563913
TI  - Imaging of chemosensory loss.
AB  - Clinical assessment of olfactory dysfunction can be challenging. Because
      olfactory disturbances comprise most chemosensory abnormalities with imaging
      findings, this article focuses on the imaging of smell disorders. This article
      reviews the normal imaging appearance of the olfactory apparatus, discusses the
      respective roles of CT and MRI, provides illustrative imaging of typical
      pathologic lesions, and discusses a clinically based imaging strategy.

PMID- 15563914
TI  - Future directions in chemosensory research.
AB  - The past two decades have witnessed phenomenal growth in chemosensory research in
      the basic sciences and clinical studies. Although chemosensory disorders today
      are recognized more widely for their marked impacts on QOL and public safety, the
      increased research focus has yet to translate into significant therapeutic
      advances for human olfactory or gustatory dysfunction. Nevertheless, it should be
      expected that active chemosensory research eventually will yield discoveries
      necessary to generate better treatment options for otolaryngologists and other
      physicians caring for smell and taste loss patients. As the understanding of
      chemosensory biology and disease pathophysiology grows, there is great promise
      that medical science will conquer the frustrating and debilitating health
      problems posed by olfactory and gustatory dysfunction. Moreover, it is likely
      that the lessons gained through chemosensory research will apply broadly to a
      range of human diseases affecting sensory modalities and the central nervous
      system.

PMID- 15563915
TI  - Anthelmintic resistance--looking to the future: a UK perspective.
AB  - The full extent of anthelmintic resistance in nematodes of farm animals is not
      known. Resistance can be detected with a faecal egg count reduction test and two
      in vitro tests, the egg hatch and larval development tests. The sensitivity of
      these two in vitro tests can be increased by using discriminating doses rather
      than calculating LD50 values. Only benzimidazole resistance can be detected with
      PCR based tests because the molecular mechanisms of resistance to levamisole and
      the macrocyclic lactones remain unknown. Resistance detection is important
      because it enables the appropriate management strategies to be put in place. The
      development of resistance is delayed by keeping sufficient parasites in refugia
      (not exposed to anthelmintic), but the necessary management details have not yet
      been validated in the field. It is probably too late to use combination products
      to delay the development of resistance, except in cattle but quarantining animals
      to prevent introduction of resistant helminths onto a farm is important. Dilution
      of resistant worms with susceptible ones is only at the preliminary research
      stage and the application of non-chemical methods of control to delay resistance
      is not yet a practical option. Extensive research is required to manage
      resistance, especially in the control of resistance in Fasciola hepatica.

PMID- 15563916
TI  - Naturally acquired attaching and effacing Escherichia coli in sheep.
AB  - In a series of experiments involving the inoculation of sheep with Escherichia
      coli O157:H7, and subsequent detailed histopathological examination of the
      intestinal mucosa, attaching-effacing (AE) lesions formed by elements of the
      natural flora were observed in 18% of animals. These incidental AE lesions
      typically were small and sparse, and were not associated with clinical disease.
      It was possible to identify further some of the lesional bacteria, revealing that
      E. coli O115 had formed lesions in one of the seven affected animals, and
      similarly E. coli O26 had formed some of the lesions in another. As AE strains,
      source flocks, housing and feed sources were diverse, a common source of lesion
      forming bacteria appears to be unlikely. It is postulated that subclinical AE
      lesions are a mechanism of persistence of AE bacteria in sheep.

PMID- 15563917
TI  - Salmonella enterica isolates from faeces of domestic reptiles and a study of
      their antimicrobial in vitro sensitivity.
AB  - From October 2001 to February 2002, the faecal samples of 305 reptiles (165
      saurians, 99 ophidians and 41 chelonians) were bacteriologically examined to
      detect Salmonella enterica. S. enterica was isolated from 73 (23.93%) faecal
      samples including 44 (60.27%) samples collected from saurians, 15 (20.55%) from
      chelonians and 14 (19.18%) from ophidians; considering the number of samples
      taken for each reptile group, S. enterica was isolated from the 36.58% of
      chelonians, 26.66% of saurians and 14.14% of ophidians. The isolates were
      distributed among 38 serotypes. Sixty-nine (94.52%) isolates were resistant to
      erythromycin. About one-third of the isolates was resistant to sulfisoxazole
      (35.61%), gentamycin (32.88%), amoxycillin (31.51%) and ampicillin (27.40%). All
      but one of the isolates were sensitive to chloramphenicol. A high percentages of
      isolates were sensitive to enrofloxacin (84.93%), nitrofurantoin (80.82%),
      trimethoprim (76.71%) and tetracycline (75.34%).

PMID- 15563918
TI  - Prevalence of antibodies to Neospora caninum in local and imported cattle breeds
      in the Kars province of Turkey.
AB  - This study investigates the seroprevalence of Neospora caninum in cattle in the
      province of Kars in north-eastern Turkey. A total of 301 serum samples, 228 from
      local breeds of cows with a history of recent abortion and the remaining 73
      collected at random from Simmental cows imported from Germany or their offspring,
      were tested for anti-Neospora antibodies by ELISA. All the serum samples from
      local breeds were negative for N. caninum antibodies, apart from one which tested
      inconclusive. In contrast six of the samples (8.2% with 95%CI: 2-14.5%) from
      Simmental cows tested positive. There was a significant difference (P<0.001) in
      the seroprevalence of N. caninum between local and Simmental breeds, even if the
      inconclusive test was considered positive, and the odds ratio of its occurrence
      in the Simmental breed was 20.3. In conclusion, it is unlikely that N. caninum
      contributes to abortion in local cattle breeds and our results also suggest that
      N. caninum was introduced to the region by the importation of Simmental cattle
      and that the vertical transmission of the parasite in cattle is important in the
      region.

PMID- 15563919
TI  - Morphology, cytochemical staining, and ultrastructural characteristics of the
      blood cells of the giant lizard of El Hierro (Gallotia simonyi).
AB  - The object of this study was to examine the erythrocytes, leukocytes and
      thrombocytes of the giant lizard of El Hierro (Gallotia simonyi) by light and
      electron (TEM) microscopy, and cytochemical staining. Smears were prepared from
      blood from the ventral coccygeal vein of 10 healthy adult lizards (five males and
      five females) from the Giant Lizard of El Hierro Reproduction and Research
      Centre, Canary Islands, Spain. The cytochemical stains used were: benzidine
      peroxidase (BP), chloroacetate esterase (CAE), alpha-naphthyl acetate esterase
      (ANAE), acid phosphatase (AP), periodic acid-Schiff (PAS), toluidine blue (TB)
      and May-Grunwald-Giemsa (MGG). Electron microscopy was also performed on all
      samples. Heterophils had granules that were heterogeneous in both size and
      electron density, and stained with BP, PAS and ANAE. Eosinophil granules were
      homogeneously electron-dense and stained for AP, CAE and ANAE. Basophils had both
      highly and moderately electron-dense granules, and stained with TB and ANAE.
      Azurophil granules were of low electron-density and stained for AP, CAE and ANAE.
      Azurophil cytoplasm was vacuolated on TEM. The cytoplasm of lymphocytes contained
      many ribosomes and was positive for AP. Monocytes had a large nucleus and a
      vacuolated cytoplasm but did not stain by any of the cytochemical methods used.
      Thrombocytes had a relatively large nucleus but little cytoplasm; they did not
      stain cytochemically. The blood cells of the giant lizards of El Hierro differ
      from those of other members of the Order Squamata both morphologically and
      cytochemically. The variation in cytochemical responses in the blood of reptiles
      makes it necessary to study species individually if meaningful clinical decisions
      are to be made.

PMID- 15563920
TI  - Blending of a conventional Mycoplasma hyopneumoniae vaccine with a positive
      marker: tracking of immunised pigs by peptide-specific antibodies raised to the
      marker component.
AB  - Highly immunodominant marker antigens simply blended to existing veterinary
      vaccines may represent a smart approach for addressing the still open issue of
      vaccination compliance. This approach was evaluated by blending a widely deployed
      Mycoplasma hyopneumoniae vaccine with a peptide-KLH (Keyhole Limpet Hemocyanin)
      conjugate as marker. Piglets were vaccinated twice with: (i) a combination of the
      M. hyopneumoniae-specific vaccine and the marker, (ii) M. hyopneumoniae-specific
      vaccine, (iii) marker alone or (iv) placebo dose only. All piglets which received
      the M. hyopneumoniae-specific vaccine/marker formulation or, as control, the
      marker blended with Montanide IMS1313 adjuvant responded to the respective
      immunisation from day 21 to 77 post vaccination as seropositive for the
      appropriate peptide and KLH. However, the responder rate to M. hyopneumoniae of
      piglets administered with M. hyopneumoniae-specific vaccine/marker was slightly
      reduced at day 35 and 49 post immunisation in comparison with piglets vaccinated
      with M. hyopneumoniae-specific vaccine alone. Accordingly, we conclude that this
      marker technology could be successfully applied to label a whole set of vaccines
      prevented that the blending process will be optimised.

PMID- 15563921
TI  - Immunoglobulins in nasal secretions of dog puppies from birth to six weeks of
      age.
AB  - In order to investigate local immune defence mechanisms in the dog, the
      concentration of immunoglobulins (Ig) G, A and M in nasal secretions (NS) and
      serum of 42 healthy, neonatal Rottweiler puppies was determined. Ig were measured
      with a commercially available, dog-specific ELISA during the first six weeks of
      life. On average, IgG was the predominant Ig isotype during the first three days
      of life. The IgA:IgG ratio changed between weeks 1 and 3 due to markedly
      decreasing IgG concentrations. Between the fourth and sixth week, IgG
      predominated again. During the first week, only 21-39% of puppies had measurable
      amounts of IgM in NS, in week 2, this percentage increased to 69%. Marked
      differences between litters and between individual puppies within litters were
      found. No puppy diseased during the observation period and all developed
      normally.

PMID- 15563922
TI  - In vitro selective suppression of feline myeloid colony formation is attributable
      to molecularly cloned strain of feline leukemia virus with unique long terminal
      repeat.
AB  - Molecularly cloned feline leukemia virus (FeLV)-clone 33 (C-33), derived from a
      cat with acute myelocytic leukemia (AML), was examined to assess its relation to
      the pathogenesis of AML and myelodysplastic syndrome (MDS). To evaluate in vitro
      pathogenicity of FeLV C-33, bone marrow colony-forming assay was performed on
      marrow cells infected with FeLV C-33 or an FeLV subgroup A strain (61E, a
      molecularly cloned strain with minimal pathogenicity). The myeloid colony-forming
      activity of feline bone marrow mononuclear cells infected with FeLV C-33 was
      significantly lower than that of cells infected with 61E. This suggests that FeLV
      C-33 has myeloid lineage-specific pathogenicity for cats, and that FeLV C-33
      infection is useful as an experimental model for investigating pathogenesis of
      MDS and AML.

PMID- 15563923
TI  - In vitro effects of four tropical plants on three life-cycle stages of the
      parasitic nematode, Haemonchus contortus.
AB  - Alcoholic extracts of four tropical plants (Zanthoxylum zanthoxyloides,
      Newbouldia laevis, Morinda lucida and Carica papaya) were screened in vitro for
      potential anti-parasitic effects against eggs, infective larvae and adult
      Haemonchus contortus. Significant effects were obtained with all four plants but
      differences were observed depending on the parasitic stage. The effects of the
      four plant extracts were similar on egg hatching and were dose dependent. In
      contrast, no dose-response relationship was found for infective larvae and adult
      worms, although more potent effects were usually observed with the highest
      concentrations. Using a larval inhibition migration test, extracts of fagara (Z.
      zanthoxyloides) were found to be less active against Haemonchus infective larvae
      than were the other plants. N. laevis was found to be highly and rapidly
      effective against adult worms. Overall, these in vitro results suggest that these
      four plants, traditionally used by small farmers in Western Africa, do possess
      anti-parasitic properties. These effects remain to be confirmed through in vivo
      studies.

PMID- 15563924
TI  - Acute toxoplasmosis in three wild arctic foxes (Alopex lagopus) from Svalbard;
      one with co-infections of Salmonella Enteritidis PT1 and Yersinia
      pseudotuberculosis serotype 2b.
AB  - Acute disseminated toxoplasmosis was diagnosed in three wild arctic foxes (Alopex
      lagopus) that were found dead in the same locality on Svalbard (Norway). The
      animals included one adult female and two 4-months-old pups. The adult fox was
      severely jaundiced. Necropsy revealed multifocal, acute, necrotizing hepatitis,
      acute interstitial pneumonia, and scattered foci of brain gliosis, often
      associated with Toxoplasma tachyzoites. One pup also had Toxoplasma-associated
      meningitis. In addition, the latter animal was infected with Yersinia
      pseudotuberculosis serotype 2b and Salmonella Enteritidis phage type 1 (PT1),
      which may have contributed to the severity of the Toxoplasma infection in this
      animal. The diagnosis of toxoplasmosis was confirmed by positive
      immunohistochemistry and detection of anti-Toxoplasma gondii antibodies in serum
      of all foxes. The animals were negative for Neospora caninum, canine distemper
      virus, canine adenovirus, and rabies virus on immunolabelling of tissue sections
      and smears.

PMID- 15563925
TI  - Cytokine responses to Cyathostominae larvae in the equine large intestinal wall.
AB  - To investigate cytokine responses in cyathostomin infection, we quantified
      mucosal interleukin-4 (IL-4), interleukin-10 (IL-10), tumour necrosis factor
      (TNF)-alpha and interferon (IFN)-gamma by reverse transcriptase-competitive
      polymerase chain reaction. The analysis was performed on large intestinal wall
      samples obtained from six anatomical sites spanning the caecum and colon of 17
      naturally exposed horses. The numbers of developing larvae (DL) and early third
      stage larvae (EL3) were ascertained using transmural illumination and pepsin
      digestion techniques, respectively. Levels of each cytokine transcript were
      correlated with local intestinal wall burdens of Cyathostominae larvae. IL-4 and
      IL-10 levels showed significant correlations with EL3 and DL burdens at several
      sites. No significant correlations were observed with IFNgamma. A pro
      inflammatory response, typified by detection of TNFalpha transcript, was observed
      at a few sites in some horses with inflammatory enteropathy associated with
      emerging or emerged larvae. However, this cytokine was measured at an
      insufficient number of sites to enable statistical analysis. Levels of IL-4, IL
      10 and IFNgamma transcript were compared between two groups: one group consisting
      of horses with low to high mucosal burdens (Group A) and the other, of horses
      with negative/negligible mucosal burdens (Group B). Significant differences in IL
      4 (P<0.001) and IL-10 (P<0.001) transcript levels were observed between the
      groups, with higher levels observed in Group A. No significant differences in
      IFNgamma were observed. Taken together, these results indicate that Th2 responses
      predominate in mucosal Cyathostominae infection prior to larval reactivation.

PMID- 15563926
TI  - Development of an antibody-detection ELISA for Fasciola hepatica and its
      evaluation against a commercially available test.
AB  - An ELISA was developed for the detection of Fasciola hepatica antibody in serum
      of cattle. The assay was applied to sera from 258 naturally infected cattle, 256
      non-infected cattle and six calves experimentally infected with F. hepatica. The
      diagnostic sensitivity and specificity of the ELISA test was 98% (95% confidence
      intervals, 96-100%) and 96% (95% confidence intervals, 93-98%) respectively at a
      cut-off value of 15% positivity. The results using sera from the experimentally
      infected calves showed that antibodies were first detected 2-4 weeks after
      infection. The ELISA test was also compared to the commercially available Bio-X
      bovine F. hepatica ELISA kit. A subset of 39 positive sera and 47 negative sera
      were selected from the samples used to evaluate the in-house test. The results
      indicated that the agreement between the two tests was almost perfect (k
      statistic=0.82).

PMID- 15563927
TI  - High expression of Bcl-xL in delayed apoptosis of canine neutrophils induced by
      lipopolysaccharide.
AB  - The expression of Bcl-2 family members, Bcl-xL, Bcl-2, Mcl-1 and Bax was
      investigated in delayed apoptosis of canine neutrophils induced by
      lipopolysaccharide (LPS). Apoptotic cell rates in neutrophils stimulated by LPS
      (100 ng/ml) were measured at 24 h incubation by TUNEL assay. The incidence of
      apoptotic neutrophils stimulated by LPS at 24 h incubation was 17.0+/-2% and that
      in non-stimulated neutrophils was 29.9+/-3%. By real-time quantitative PCR
      analysis, it was indicated that Bcl-xL and Bax levels in canine neutrophils were
      significantly affected by LPS stimulation. The levels of Bcl-xL, Bcl-2, Mcl-1 and
      Bax transcripts at 9 h incubation in neutrophils stimulated by LPS (100 ng/ml)
      were increased by about 80.4-, 1.9-, 1.4- and 5.3-folds, in comparison to those
      in non-stimulated neutrophils, respectively. These results indicated that Bcl-xL
      was proved have an important role in the inhibition of canine neutrophil
      apoptosis by LPS.

PMID- 15563928
TI  - Preferential and non-selective cyclooxygenase inhibitors reduce inflammation
      during lipopolysaccharide-induced synovitis.
AB  - Synovitis in horses is frequently treated by administration of non-steroidal anti
      inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX
      2). Constitutively expressed COX-1 is involved in physiologic functions such as
      maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites
      of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced
      gastrointestinal side effects as compared to non-selective COX inhibitors. The
      objective of the present study was to compare the anti-inflammatory effects of
      the preferential COX-2 inhibitor etodolac with the non-selective COX inhibitor
      phenylbutazone in horses with lipopolysaccharide (LPS)-induced synovitis. Three
      groups of horses (n=6) received no treatment, phenylbutazone (4.4 mg/kg, IV,
      q12h), or etodolac (23 mg/kg, IV, q12h), respectively, 2-h following injection of
      LPS into one middle carpal joint. Synovial fluid was analyzed for white blood
      cell (WBC) count, and TXB2 and PGE2 levels. Phenylbutazone and etodolac
      significantly reduced WBC count 6 and 24-h following injection of LPS compared to
      untreated horses. In addition, both drugs significantly reduced PGE2 levels
      (P<0.05) 6-h following LPS injection, whereas the probable COX-1 prostanoid TXB2
      was significantly reduced by phenylbutazone (P<0.05), but not etodolac. Etodolac
      may serve as a more selective anti-inflammatory agent than phenylbutazone for
      treatment of equine synovitis.

PMID- 15563930
TI  - The relationship between oral health and nutrition in older people.
AB  - The oral health of older people is changing with reducing numbers of people
      relying on complete dentures for function, and retaining some natural teeth.
      Despite this there are substantial numbers of older people whose ability to chew
      foods is compromised by their oral health status, either because they have few or
      no natural teeth. This alteration results in individuals selecting a diet that
      they can chew in comfort. Such diets are low in fruits and vegetables intake with
      associated reduction in both non-starch polysaccharide and micronutrient intakes.
      There is also a trend for reduced dietary intake overall. Salivary flow and
      function may have an impact in relation to the ability to chew and swallow.
      Whilst there are few differences in salivary function in fit healthy unmedicated
      subjects, disease resulting in reduced salivary flow and particularly
      polypharmacy, with xerostomia as a side effect, are likely to have a role in
      older people. This paper explores the relationships between oral health status
      and food's choice and discusses the potential consequences for the individual of
      such dietary change.

PMID- 15563931
TI  - Food intake and ageing--the role of the gut.
AB  - Healthy ageing is associated with decreased appetite and energy intake and this
      is generally associated with weight loss after about 70 years of age. The
      mechanisms responsible for this 'physiological' anorexia are not well understood,
      but it may predispose to the development of protein-energy malnutrition in older
      people, which is associated with increased morbidity and mortality. Many sensory
      and social factors, including olfactory changes and economic status, contribute
      to under-nutrition in older people; however, normal ageing is associated with a
      number of significant changes in gastrointestinal function. The control of
      appetite is complex but it is clear that gastrointestinal signals are important
      in the regulation of appetite and food intake. This review examines the role of
      small intestinal hormones and gastrointestinal motor function in the observed
      changes to appetite and food intake in older people.

PMID- 15563932
TI  - Changes in upper gastrointestinal physiology with age.
AB  - Diseases of the upper gastrointestinal tract such as peptic ulceration and
      gastric cancer become more common and more severe with advancing age. In the
      normal stomach and duodenum, there is a balance between mucosal protective
      mechanisms and endogenous (gastric acid and pepsin) and exogenous aggressive
      factors. The high incidence of gastrointestinal pathology seen in older age
      groups is not related to increase in the secretion of endogenous aggressive
      factors. Recent work suggests that gastrointestinal mucosal protective mechanisms
      are impaired with age. The roles in the gastrointestinal tract of molecules that
      have been implicated in mucosal repair, such as trefoil peptides and matrix
      components, are beginning to be elucidated and their study in older people is
      essential to ensure appropriate, efficient, cost-effective management of gastric
      pathology in the elderly. Strategies to improve the management of upper
      gastrointestinal diseases in older people will reduce mortality and improve
      quality of life.

PMID- 15563933
TI  - Alterations in stomach ghrelin production and in ghrelin-induced growth hormone
      secretion in the aged rat.
AB  - Ghrelin is a recently discovered stomach hormone that stimulates growth hormone
      (GH) secretion, food intake, adiposity, and growth. In this report, we present
      new and previously published data from our laboratory showing that stomach
      ghrelin production and secretion are increased, and that GH release in response
      to exogenous ghrelin is enhanced in the aged rat. Together, these data suggest
      that the aging associated decline in GH secretion is not due to a reduction in
      stomach ghrelin secretion or a stimulatory action on GH release.

PMID- 15563934
TI  - Age-related changes in the response of intestinal cells to parathyroid hormone.
AB  - The concept of the role(s) of parathyroid hormone (PTH), has expanded from that
      on acting on the classical target tissues, bone and kidney, to the intestine
      where its actions are of regulatory and developmental importance: regulation of
      intracellular calcium through modulation of second messengers and, activation of
      mitogenic cascades leading to cell proliferation. Several causes have been
      postulated to modify the hormone response in intestinal cells with ageing, among
      them, alterations of PTH receptor (PTHR1) binding sites, reduced expression of G
      proteins and hormone signal transduction changes. The current review summarizes
      the actual knowledge regarding the molecular and biochemical basis of age
      impaired PTH receptor-mediated signaling in intestinal cells. A fundamental
      understanding of why PTH functions are impaired with age will enhance our
      understanding of its importance in intestinal cell physiology.

PMID- 15563935
TI  - Mucosal immunity and tolerance in the elderly.
AB  - Age-associated dysregulation of the immune system of the gastrointestinal (GI)
      tract has been well documented for both secretory (S)-IgA immunity and oral
      tolerance. Thus, impaired antigen-specific Ab responses in aged animals and the
      elderly have been reported. Further, it has been shown that gut-associated
      lymphoreticular tissue (GALT) mediated immune responses are more susceptible to
      aging than are lymphoid tissues involved in peripheral immunity. Aging also
      impairs oral tolerance, which may be of central importance for maintaining GI
      homeostasis. Thus, as early as 6-8-month-old mice failed to establish systemic
      unresponsiveness to orally introduced antigens. Despite these studies, the
      precise mechanisms for impaired GI tract immune system responses remain unclear.
      The evidence of reduced sizes of Peyer's patches through aging suggests that age
      associated mucosal dysregulation may be the result of mucosal inductive tissue
      dysfunction. Indeed, the frequencies of naive CD4+ T cells and dendritic cells
      (DCs) in Peyer's patches of aged mice were reduced and this led to a lack of
      essential cytokine synthesis for the induction of either S-IgA immunity or oral
      tolerance.

PMID- 15563936
TI  - Ageing of the enteric nervous system.
AB  - The intrinsic neurones of the enteric nervous system (ENS) play a fundamental
      role in the regulation of gastrointestinal functions. Although much remains to be
      learnt about the changes that take place in intestinal nerves during ageing,
      evidence suggests that selective neurodegeneration may occur in the ageing ENS.
      Age-associated changes in intestinal innervation may contribute to the
      gastrointestinal disorders that increase in incidence in the elderly, such as
      dysphagia, gastrointestinal reflux and constipation. A number of other factors,
      such as immobility, co-morbidity, and side effects of therapeutic medication for
      other disorders however, are also likely to contribute to the aetiology of these
      conditions. An important finding in rodents is that the neuronal losses that take
      place in the ENS during ageing may be prevented by calorie restriction; an
      indication that diet may influence gastrointestinal ageing. Thus, it is of
      importance to understand not only how the ENS changes during 'normal' ageing, but
      also how external factors contribute to these changes. Here, current knowledge of
      how intestinal innervation is affected during normal ageing and how these changes
      may impact upon gastrointestinal physiology are reviewed.

PMID- 15563937
TI  - Aging and gastrointestinal smooth muscle.
AB  - The present review is an attempt to put into perspective the available
      information on the putative changes in cellular mechanisms of the contractile
      properties of the aging gastrointestinal (GI) smooth muscle. Information on
      smooth muscle of the GI tract is scanty. Smooth muscle cells from old rats (32
      months old) exhibit limited cell length distribution and diminished
      contractility. The observed reduced contractile response may be due to the effect
      of aging on signal transduction pathways, especially an inhibition of the
      tyrosine kinase-Src kinase pathway, a reduced activation of the PKCalpha pathway,
      a reduced association of contractile proteins (HSP27-tropomyosin, HSP27-actin,
      and actin-myosin). Levels of HSP27-phosphorylation are also reduced compared to
      adult rats. Regulation of GI motility is a complex mechanism of signal
      transduction and interaction of signaling and contractile proteins. It is
      suggested that further studies to elucidate the role of HSP27 in aging smooth
      muscle of the GI tract are needed.

PMID- 15563938
TI  - Intrinsic ageing of gut epithelial stem cells.
AB  - The maintenance of integrity of gut epithelium is essential for the well being of
      the organism throughout life. Gut epithelium is maintained through a carefully
      controlled balance between cell loss and renewal, which is sustained by the
      proliferation of the epithelial stem cells. Although these stem cells show no
      intrinsic limit to their proliferative capacity, recent evidence indicates that
      they suffer important functional impairments during the course of ageing. This
      paper reviews what is currently known about intrinsic ageing of gut epithelial
      stem cells and its functional consequences.

PMID- 15563939
TI  - Age-related loss of EGF-receptor related protein (ERRP) in the aging colon is a
      potential risk factor for colon cancer.
AB  - Although in Fischer-344 rats, aging is associated with increased activation of
      EGF-receptor (EGFR) in mucosa of much of the gastrointestinal tract, including
      the colon, regulation of this process is poorly understood. We hypothesize that
      loss of suppressor of EGFR may partly be responsible for this process. To test
      this hypothesis, we examined the expression of EGFR related protein (ERRP), a
      recently identified negative regulator of EGFR, in the colonic mucosa during
      aging and following administration of the colonic carcinogen dimethylhydrazine
      (DMH) that resulted in the formation of aberrant crypt foci (ACF), which are
      considered to be precursor of adenoma and carcinoma. In Fischer-344 rats, aging
      is associated with increased activation of EGFR in the colonic mucosa, as
      evidenced by 30-35% increase in the levels of tyrosine phosphorylated EGFR in the
      proximal and distal colon of aged (20-22 months old) than in young (4-6 months
      old) rats. In contrast, the levels of ERRP in both regions of the colon of aged
      rats were decreased by 50-60%, compared to their younger counterparts.
      Administration of DMH, which induced a greater number of ACF in the colon of aged
      rats than in young animals, resulted in a corresponding reduction in ERRP in the
      colon. These results suggest that loss of ERRP expression is a common event
      during aging and early stages of chemically induced colon cancer. We also suggest
      that loss of ERRP could be a risk factor for developing colorectal cancer in the
      older population.

PMID- 15563941
TI  - Stem/progenitor cells in lung morphogenesis, repair, and regeneration.

PMID- 15563942
TI  - Lessons from a canine model of compensatory lung growth.
AB  - For over a century, canines have been used to study adaptation to surgical lung
      resection or pneumonectomy (PNX) that results in a quantifiable and reproducible
      loss of lung units. As reviewed by Schilling (1965), the first successful
      experimental pneumonectomies were performed in dogs and rabbits in 1881. By the
      early 1920s, it was appreciated that dogs can function normally with one
      remaining lung that increases in volume to fill the thoracic cavity (Andrus,
      1923; Heuer and Andrus, 1922; Heuer and Dunn, 1920); these pioneering
      observations paved the way for surgeons to perform major lung resection in
      patients. Reports in the 1950s (Schilling et al., 1956) detail surprisingly well
      preserved work performance in dogs following staged resection of up to 70% of
      lung mass. Since then, the bulk of the literature on post-PNX adaptation has
      shifted to rodents, especially for defining molecular mediators of compensatory
      lung growth. Because rodents are smaller and easier to handle, more animals can
      be studied over a shorter duration, resulting in time and cost savings. On the
      other hand, key aspects of lung anatomy, development, and time course of response
      in the rodent do not mimic those in the human subject, and few rodent studies
      have related structural adaptation to functional consequences. In larger mammals,
      anatomical lung development more closely resembles that in humans, and
      physiological function can be readily measured. Because dogs are natural
      athletes, functional limits of compensation can be characterized relatively
      easily by stressing oxygen transport at peak exercise. Thus, the canine model
      remains useful for relating structure to function, defining sources and limits of
      adaptation as well as evaluating therapeutic manipulation. This chapter
      summarizes key concepts of compensatory lung growth that have been consolidated
      from canine studies: (i) structure-function relationships during adaptation, (ii)
      dysanaptic (unequal) nature of compensation, and (iii) signals for initiation of
      cellular growth.

PMID- 15563943
TI  - Airway glandular development and stem cells.
AB  - Submucosal glands in the lung play important roles in several hypersecretory lung
      disease processes, including chronic bronchitis, asthma, and cystic fibrosis. In
      this context, submucosal glands undergo abnormal growth and differentiation
      through processes that are poorly understood. To better understand the
      pathophysiological mechanisms that lead to submucosal gland hypertrophy and
      hyperplasia in the adult human lung, efforts have been made to dissect the
      molecular signals and cell types responsible for normal submucosal gland
      development in the airway. Such studies have revealed a close relationship
      between progenitor?stem cell phenotypes in the surface airway epithelia and
      submucosal glands, and thus it has been suggested that submucosal glands serve as
      a protective niche for surface airway epithelial stem cells. Furthermore, the
      pluripotent progenitor cells that exist in the surface airway epithelium, which
      have the capacity to differentiate into ciliated, secretory, intermediate, and
      basal cells, also have a developmental capacity for submucosal glands. This
      putative adult stem cell compartment of the airway epithelium has been the focus
      of research attempting to identify molecular markers for signaling pathways that
      control stem cell phenotypes and their capacity for proliferation and
      differentiation following airway injury.

PMID- 15563944
TI  - Gene expression studies in lung development and lung stem cell biology.

PMID- 15563945
TI  - Mechanisms and regulation of lung vascular development.

PMID- 15563946
TI  - The engineering of tissues using progenitor cells.
AB  - The "engineering" of a tissue implies that it can be constructed by assembling
      the necessary components. However, tissues are formed through an evolving,
      interactive process, not through a collection of parts. This chapter focuses on
      the biology of the progenitor cell, the native precursor to new tissue, and its
      role in neogenesis, or the de novo generation of functional tissue. We present a
      working hypothesis for the generation of parenchymal cell populations and use
      this hypothesis as a basis for analysis of three parenchymal populations,
      epidermal cells, hepatocytes of the liver, and pancreatic islets, with a view
      toward what impact this information will have on the development of cell
      therapies. By comparing developmental processes, response to injury and disease,
      and behavior in vitro, we conclude that the adult progenitor cell retains the
      potential for substantial growth and organ neogenesis and that its biological
      properties make it the cell of first choice for the engineering of tissues.

PMID- 15563947
TI  - Adult bone marrow-derived hemangioblasts, endothelial cell progenitors, and EPCs.
AB  - Long before their existence was proven, work with blood islands pointed to the
      existence of hemangioblasts in the embryo, and it was widely accepted that such
      cells existed. In contrast, though evidence for adult hemangioblasts appeared at
      least as early as 1932, until quite recently, it was commonly assumed that there
      were no adult hemangioblasts. Over the past decade, these views have changed, and
      it is now generally accepted that a subset of bone marrow cells or their progeny
      can and do function as adult hemangioblasts. This chapter will examine the basic
      biology of bone marrow-derived hemangioblasts and endothelial cell progenitors
      (angioblasts) and the relationship of these adult cells to their embryonic
      counterparts. Efforts to define the endothelial cell progenitor phenotype will
      also be discussed, though to date, there is no consensus on the definitive adult
      phenotype, probably because there are multiple phenotypes and because the cells
      are plastic. Also examined are the putative roles of bone marrow-derived cells in
      vascular homeostasis and repair, including both their ability to differentiate
      and contribute directly to vascular repair, as well as to promote vascular growth
      by secreting pro-angiogenic factors. Finally, the use of bone marrow cells as
      therapeutic tools will be addressed.

PMID- 15563948
TI  - Synthetic extracellular matrices for tissue engineering and regeneration.
AB  - The need for replacement tissues or organs requires a tissue supply that cannot
      be satisfied by the donor supply. The tissue engineering and regeneration field
      is focused on the development of biological tissue and organ substitutes and may
      provide functional tissues to restore, maintain, or improve tissue formation.
      This field is already providing new therapeutic options to bypass the limitations
      of organ?tissue transplantation and will likely increase in medical importance in
      the future. This interdisciplinary field accommodates principles of life sciences
      and engineering and encompasses three major strategies. The first, guided tissue
      regeneration, relies on synthetic matrices that are conductive to host cells
      populating a tissue defect site and reforming the lost tissue. The second
      approach, inductive strategy, involves the delivery of growth factors, typically
      using drug delivery strategies, which are targeted to specific cell populations
      in the tissues surrounding the tissue defect. In the third approach, specific
      cell populations, typically multiplied in culture, are directly delivered to the
      site at which one desires to create a new tissue or organ. In all of these
      approaches, the knowledge acquired from developmental studies often serves as a
      template for the tissue engineering approach for a specific tissue or organ. This
      article overviews the development of synthetic extracellular matrices (ECMs) for
      use in tissue engineering that aim to mimic functions of the native ECM of
      developing and regenerating tissues. In addition to the potential therapeutic
      uses of these materials, they also provide model systems for basic studies that
      may shed light on developmental processes.

PMID- 15563949
TI  - Integrins and angiogenesis.
AB  - The growth of new blood vessels is a dynamic yet highly regulated process that
      depends on coordinated signaling by growth factor and cell adhesion receptors. As
      part of the molecular program regulating angiogenesis, endothelial cells acquire
      a proliferative and invasive phenotype but also show increased susceptibility to
      apoptotic stimuli. Integrins are the principle adhesion receptors used by
      endothelial cells to interact with their extracellular microenvironment, and
      integrin-mediated interactions play a critical role in regulating cell
      proliferation, migration, and survival. Alterations in the repertoire and?or
      activity of integrins, as well as the availability and structural property of
      their ligands, regulate the vascular cell during the growth or repair of blood
      vessels.

PMID- 15563950
TI  - Virulence characteristics of Escherichia coli isolates obtained from broiler
      breeders with salpingitis.
AB  - Thirty isolates of Escherichia coli from broiler breeders with salpingitis were
      studied. Using the slide agglutination test, the isolates were found to belong to
      serogroups O1, O2, O5, O36, O45, O53 and O78. Pathogenicity for day-old chicks
      was determined by air sac inoculation and isolates were categorized as having
      high, intermediate or low virulence. Growth on iron starvation medium was
      observed together with aerobactin production. Based on the results of in vitro
      adherence tests, attachment to oviduct epithelium from old birds was found to be
      superior to that observed using corresponding material from young birds. DNA
      hybridization testing for type 1, P, and S fimbriae revealed predominant
      expression of type 1, correlating with mannose-sensitive hemagglutination using
      guinea-pig erythrocytes. In this study, P and S fimbriae were not considered to
      be important adherence factors. Study findings would suggest that, as far as
      salpingitis is concerned, type 1 fimbriae can play an important role in E. coli
      infection in breeders. An interesting result to emerge from the study was the
      observation that E. coli isolates were completely resistant to serum from young
      breeders, whereas they were completely sensitive using serum from older breeders.
      Based on serogroups involved, pathogenicity for day-old chicks and virulence
      indicators, the salpingitis isolates were similar to those from cases of chronic
      respiratory disease.

PMID- 15563951
TI  - Expression and purification of recombinant swine interleukin-4.
AB  - The swine interleukin-4 (SwIL-4) cDNA was cloned by RT-PCR. It was expressed
      using an expression vector pQE30 in E. coli, a baculovirus AcNPV vector pVL1392
      in insect cells, and a pCAGGS vector in mammalian cells. The rSwIL-4 proteins
      expressed from bacteria and insect cells were purified using a chelating affinity
      column and a mAb-coupled immunoaffinity column. The amount of the products and
      their bioactivities were compared. All recombinant cytokines were efficiently
      reacted with the specific antibodies and the molecular weight of rSwIL-4 was
      approximately 16 kDa in E. coli, 15 and 18 kDa in insect cells, and 15 and 20 kDa
      in mammalian cells. Variations of molecular weight observed in insect and
      mammalian cells were probably due to different modification ways of
      glycosylation. All these recombinant proteins retained their antigenicity and
      were biologically active in inducing human TF-1 cell proliferation in vitro. The
      simple purification method will make it possible to evaluate the in vitro and in
      vivo effects of IL-4 in pigs.

PMID- 15563952
TI  - Nucleotide sequence of the matrix protein gene of avian paramyxovirus, serotype
      3b: evidence on another member of the suggested new genus of the subfamily
      Paramyxovirinae.
AB  - The complete nucleotide sequence of the gene encoding the matrix protein (M) of
      the avian paramyxovirus, serotype 3b (APMV-3b), has been determined by means of
      the direct sequencing of viral RNA using reverse transcriptase reaction. The
      adjacent portions of the neighboring phosphoprotein (P) and fusion (F) protein
      genes were also sequenced that permitted to determine the consensus sequence of
      the viral genome, the poly(A) tract, downstream and upstream non-coding portions
      of the P and F genes, respectively, as well as the corresponding intergenic
      regions. The gene is 1478 nucleotides long with a protein-coding sequence of 1194
      nucleotides. The deduced protein consists of 398 amino acids with a calculated MW
      44,465. According to the multalignment and phylogenetic analyses, the APMV-3b M
      protein has shown the closest relatedness towards Newcastle disease virus (NDV)
      which has recently been suggested to be excluded from the Rubulavirus genus and
      assigned (together with APMV-6) to a new Avulavirus genus within the subfamily
      Paramyxovirinae of the Paramyxoviridae family. On the basis of the M protein
      genetic multalignment, phylogenetic relationships, bipartite nuclear localization
      signal identification in combination with the cysteine residues distribution, and
      by the degree of intrageneric heterogeneity, the APMV-3b is proposed to be
      another member (together with NDV and APMV-6) of the new genus.

PMID- 15563953
TI  - Molecular epidemiology of virulent Rhodococcus equi from foals in Brazil:
      virulence plasmids of 85-kb type I, 87-kb type I, and a new variant, 87-kb type
      III.
AB  - We investigated the prevalence of virulent Rhodococcus equi in clinical isolates
      from 41 foals (19 sporadic and seven endemic cases) in Brazil between 1991 and
      2003. Of the 41 virulent isolates, six contained an 85-kb type I plasmid, 33
      contained an 87-kb type I plasmid, both of which have been found in isolates from
      the Americas, and the remaining two contained a new variant, which did not
      display the EcoRI, EcoT22I and BamHI digestion patterns of the 11 representative
      plasmids already reported (85-kb types I-IV; 87-kb types I and II; 90-kb types I
      V). We tentatively designated the new variant as the '87-kb type III' plasmid,
      because its BamHI digestion pattern is similar to that of the 87-kb type I
      plasmid. This is the first report of the molecular epidemiology surveillance of
      virulent R. equi in clinical isolates from Brazilian foals.

PMID- 15563954
TI  - Protection of Brucella abortus RB51 revaccinated cows, introduced in a herd with
      active brucellosis, with presence of atypical humoral response.
AB  - It is a dogma, that RB51 vaccination does not induce antibodies that interfere
      with Brucellosis diagnosis, therefore any animal positive to serological test is
      considered as an infected animal. To determine protection against Brucellosis
      virulent field strain, 35 pregnant cows from a free-Brucellosis herd, previously
      vaccinated as calves with 1 x 10(10) CFU of RB51, were revaccinated with RB51
      reduced dose, and then introduced into a herd with an active outbreak. Seventeen
      cows resulted positive in card test after revaccination. All 35 pregnant
      revaccinated cows had normal parturition; nevertheless, RB51 vaccine strain was
      isolated from milk and vaginal exudates from two cows after delivery at day 120
      post-revaccination. At 150 days post-revaccination, two cows were positives to
      card and rivanol test and the field virulent strain was isolated. Revaccination
      with a reduced dose of RB51 in endemic zones did not cause abortion and protected
      94% of animals against field infection, but caused an atypical response to
      conventional serological tests.

PMID- 15563955
TI  - Bacterial flora of free-living double-crested cormorant (Phalacrocorax auritus)
      chicks on Prince Edward Island, Canada, with reference to enteric bacteria and
      antibiotic resistance.
AB  - Cloacal and pharyngeal swabs from 100 tree-nesting Double-crested cormorant (DCC)
      chicks were examined by culture for commensal and potentially pathogenic
      bacteria. No Salmonella or Erysipelothrix were isolated from the cloacal swabs.
      Twenty-two cloacal swabs were positive for Campylobacter, of which 14 were C.
      jejuni, C. coli, and 1 C. lari. None belonged to common serotypes isolated from
      humans or animals in recent years in Canada. Tests for antimicrobial drug
      resistance among 187 commensal Escherichia coli isolates from the cloacal swabs
      indicated that < or =5% were resistant to any of the 12 antibiotics tested. This
      contrasts with the frequently high resistance rates among E. coli isolates from
      poultry. Pharyngeal swabs from DCC were negative for Pasteurella multocida.
      Culture of cloacal swabs from 100 ground-nesting DCC chicks resulted in the
      recovery of 19 Salmonella isolates, all of which were S. enterica serotype
      Typhimurium. None of these isolates were resistant to any of the 12 antibiotics
      tested. Altogether, these findings suggest that DCC from this region are not
      being colonized with commensal or potentially pathogenic enteric bacteria from
      agricultural or human sources and that enteric bacteria isolated from these birds
      are unlikely to contribute to a gene pool of antimicrobial drug resistance.

PMID- 15563957
TI  - Effect of erythropoietin on endothelial cell apoptosis induced by high glucose.
AB  - Erythropoietin (Epo) has been reported to inhibit apoptosis of neuron and
      erythroid cells. In this study, we examined an effect of high glucose on
      apoptosis of endothelial cells and investigated an anti-apoptotic effect of Epo.
      Human aortic endothelial cells were incubated with normal or high glucose for 72
      h, and apoptotic cells were detected by TUNEL assay. Simultaneously, Epo (100
      U/ml) was added to the high glucose medium to examine an inhibitory effect on the
      apoptosis induced by high glucose. Activity of caspase-3 was also measured using
      a specific substrate. To investigate a possible mechanism of Epo's action on
      apoptosis, phosphorylation of Akt was examined by applying Epo. Incubation with
      high glucose increased apoptosis of endothelial cells, whereas this effect was
      prevented by co-incubation with Epo. Caspase-3 activity was also increased (1.4
      fold) by incubation with high glucose, and the activation of caspase-3 was
      normalized to the control level by co-incubation with Epo. Furthermore, Epo
      induced phosphorylation of Akt in dose-dependent manner. In conclusion, we
      demonstrated that incubation with high glucose activated caspase-3 and induced
      apoptosis of endothelial cells. Epo was shown to phosphorylate Akt, leading to
      the inhibition of caspase-3 activation and apoptosis induced by high glucose.
      These results suggest that reduced production of Epo in patients with end-stage
      of nephropathy may accelerate diabetic angiopathy and that replacing therapy with
      Epo might inhibit endothelial cell apoptosis and diabetic angiopathy.

PMID- 15563958
TI  - Evalution of oxidative stress in diabetic animals by in vivo electron spin
      resonance measurement--role of protein kinase C.
AB  - Enhanced oxidative stress may be an important contributor to the pathogenesis of
      diabetic vascular complication. Although hyperglycemia-induced oxidative stress
      in diabetes has been well documented, exact source in vivo remains to be
      elucidated. Here we report a role of protein kinase C (PKC) in oxidative stress
      in diabetic animals using a technique of in vivo electron spin resonance (ESR)
      measurement that has been developed for direct and non-invasive analysis of free
      radical generation in living animals. First, using this measurement, we confirmed
      that streptozotocin-induced diabetic rats which showed a significant increase in
      free radical generation, which was restored by alpha-tocopherol treatment.
      Treatment of PKC inhibitor CGP41251 (50 mg/kg) or NAD(P)H oxidase inhibitor
      apocynin (5 mg/kg) restored the increased free radical generation in those
      diabetic animals. In conclusion, the present study provided the evidence that PKC
      dependent activation of vascular NAD(P)H oxidase may be a major source in
      enhanced oxidative stress in diabetes in vivo. This may contribute to the
      pathogenesis of diabetic vascular complications.

PMID- 15563959
TI  - Islet transplantation: a realistic alternative for the treatment of insulin
      deficient diabetes mellitus.
AB  - Diabetes mellitus is a devastating disease and the WHO [World Health Report,
      World Health Organization, 2002] (World Health Organization) expects that the
      number of diabetic patients will increase to 300 million by the year 2025. Type 1
      diabetes results from an autoimmune-mediated destruction of the insulin-secreting
      beta-cells in the islets of Langerhans of the pancreas, whereas Type 2 diabetes
      is a disease of the older population which is due to systemic insulin resistance
      and reduced insulin secretion by the pancreatic beta-cells. Surgical resection of
      the pancreas may also cause insulin-dependent diabetes depending on the size of
      the remaining pancreas. The long-term complications of diabetes are a direct
      result of the constantly elevated levels of blood glucose in the absence of an
      effective insulin treatment. Recent prospective studies such as the diabetes
      control and complication trial (DCCT) [N. Engl. J. Med. 329 (1993) 977] and the
      UK prospective diabetes study [Lancet 352 (1998) 837] have convincingly
      demonstrated that improved blood glucose control in all type diabetes reduces the
      risk of the development of the secondary complications of diabetes. Despite
      intensive insulin therapy, most individuals with insulin deficient diabetes are
      unable to maintain a blood glucose level in the normal range at all times.
      Therefore, the only way to ensure the long-term health of patients with diabetes
      is find a way of maintaining constant normoglycemia. It seems logical that the
      replacement of the islet tissue itself, either by transplanting a vascularized
      pancreatic allograft or by transplanting purified pancreatic islet cells, offers
      a better approach than simply replacing insulin that has been lost. In this
      article, we outline the major achievements made recently in the development of
      therapeutic islet transplantation applications and offer an explanation as to why
      islet transplantation seems to be an ideal solution for absolute insulin
      deficient diabetes.

PMID- 15563960
TI  - Serum high sensitivity C-reactive protein is associated with carotid intima-media
      thickness in type 2 diabetes.
AB  - BACKGROUND: High sensitivity C-reactive protein (hsCRP) is more sensitive than
      standard C-reactive protein (CRP) assay in evaluating the risk of coronary heart
      disease and other atherosclerotic events. By this time, there are several reports
      that type 2 diabetic subjects have higher serum levels of hsCRP than those of non
      diabetic subjects. However, there are few reports about factors which have
      influence upon the level of serum hsCRP in type 2 diabetic subjects. We had
      evaluated the association of serum hsCRP level with risk factors of
      cardiovascular diseases and carotid intima-media thickness (IMT) in type 2
      diabetic subjects. METHODS: One hundred and five patients (59 men and 46 women)
      with type 2 diabetes were recruited. Subjects with severe cardiovascular diseases
      were excluded. All subjects were undergone carotid ultrasonography for evaluation
      of carotid IMT. Serum hsCRP concentrations were measured. RESULTS: Serum hsCRP
      level was correlated with mean left IMT (r = 0.366, P = 0.003), maximal left IMT
      (r = 0.370, P = 0.002), mean right IMT (r = 0.281, P = 0.023) and maximal right
      IMT (r = 0.370, P = 0.002), body mass index (r = 0.377, P < 0.001), waist
      circumference (r = 0.342, P < 0.001), waist-hip ratio (r = 0.229, P = 0.020),
      serum total cholesterol (r = 0.202, P = 0.024), serum triglyceride (r = 0.292, P
      = 0.022) and serum low-density lipoprotein (r = 0.133, P = 0.044). CONCLUSION:
      Our result shows that serum hsCRP level is correlated with carotid IMT and the
      risk factors of cardiovascular diseases and may be useful to predict accelerated
      atherosclerotic process in type 2 diabetic subjects.

PMID- 15563961
TI  - Possible contribution of adipocytokines on diabetic neuropathy.
AB  - Neuropathy is one of the typical features of chronic complications of diabetes
      mellitus. Recent analyses indicate that subjects with impaired glucose tolerance
      (IGT) already have disturbance of peripheral nerve function. To test the role of
      adipocytokines, that tend to be abnormal in IGT subjects, on diabetic neuropathy,
      we analyzed the relationship between plasma adipocytokine levels (TNFalpha,
      adiponectin, and leptin) and nerve conduction velocity in 105 type 2 diabetic
      subjects (M/F = 66/39, age = 60.8 +/- 11.8 years, BMI = 24.7 +/- 5.0kg/m2).
      Adipocytokines were measured by ELISA, and motor conduction velocity (MCV) and
      sensory conduction velocity (SCV) in median, ulnar, and tibial nerve were
      measured by electrical stimulation. Motor conduction velocity and SCV were
      corrected by age to be 1.0 as the normal value, and the average of three nerves
      were used to be the representative value. Relationship between corrected MCV or
      corrected SCV as a dependent variable and the duration of diabetes, HbA1C, BMI,
      TNFalpha, adiponectin, and leptin concentrations as independent variables were
      analyzed by multiple regression. Duration of diabetes and HbA1C were highly
      related with both corrected MCV (P < 0.02 and P < 0.001) and SCV (P < 0.02 and P
      < 0.05) by this analysis. Only corrected SCV was related significantly with
      TNFalpha (P < 0.05), and close to significantly with leptin (P = 0.059)
      concentrations. These results indicate that increased plasma glucose levels and
      duration of diabetes are the major factors that modulate diabetic neuropathy.
      However, nerve function may be affected by plasma cytokine levels like TNFalpha,
      and this effect was more significant on sensory nerves than motor nerves. The
      present results suggest that adipocytokines may play a role not only on
      angiopathy but also on neuropathy in diabetics.

PMID- 15563962
TI  - A case of type 2 diabetes with high levels of plasma and urinary C-peptide.
AB  - By screening 204 diabetes patients, a male with age 38 was found to have
      increased C-peptide levels in plasma (over 6 ng/ml) and urine (430 microg/day),
      both of which were the highest among the screened subjects. He developed type 2
      diabetes at age 31, without history of obesity (weight was 52 kg and height 170
      cm). He had bilateral testicular atrophy. Fasting plasma glucose level was 160
      mg/dl and HbA1c was 8% at age 38. There was hypertriglycemia (290-662 mg/dl).
      There were no abnormal peaks of IRI or CPR in the serum fractionated by gel
      filtration (Biogel P 30). Molar ratio of p-CPR/s-IRI was 10.8. Islet cell
      antibody, anti-insulin binding antibody and anti-insulin receptor antibody were
      negative. LSH and FSH were both elevated, and free testosterone was decreased.
      TSH and Leptin levels were elevated. Other laboratory data were within normal
      range. CT scan revealed fatty liver and horse-shoe kidney. These clinical
      pictures do not match the criteria to known syndromes associated with diabetes.
      Although the single case report is insufficient to discuss the C-peptide
      mechanism of action, this case may give us a hint to understand an aspect of the
      pathophysiology of C-peptide's bioactivity dysfunction.

PMID- 15563963
TI  - Efficacy of glimepiride in type 2 diabetic patients treated with glibenclamide.
AB  - Multicentric study was conducted to evaluate the efficacy of glimepiride in the
      oral hypoglycemic agents therapy of type 2 diabetic patients treated with
      glibenclamide so far, and to claim an adequate use of this new generation
      sulfonylurea. In 66 diabetic outpatients, glibenclamide was switched to
      glimepiride. After 6 months' therapy, a significant reduction in fasting plasma
      IRI was observed in relatively hyperinsulinemic patients. In addition, weight
      reduction was achieved in patients with insulin resistance during this study.
      These findings suggest that glimepiride improves insulin resistance in
      hyperinsulinemic patients treated with glibenclamide. Also, glimepiride is
      favored especially for overweight, insulin-resistant patients inadequately
      controlled by glibenclamide.

PMID- 15563964
TI  - Development of web-based diabetic patient management system using short message
      service (SMS).
AB  - We developed a blood glucose management system using the Internet and short
      message service (SMS) which can lessen the social economic burden and materialize
      an individualized diabetes mellitus management. A total of 185 diabetic patients
      participated in this study and their mean age was 42.4 years old (8-79 year-old).
      Participants sent their self-measured blood glucose levels, medication and its
      dosages, amount of meal, and degree of exercise to their health providers in this
      specialized web-based diabetes management system for 3 months. The health
      providers consisting of endocrinology specialists, dietitians, and nurses sent
      recommendations for individualized diabetes management according to the data on
      the web. Laboratory tests including lipid profiles and glycated hemoglobin
      (HbA1c), and a survey of satisfaction about this system were performed before and
      after the study period. The mean HbA1c improved from 7.5 +/- 1.5 to 7.0 +/- 1.1%
      after using the management program (P = 0.003). The mean serum triglyceride and
      HDL-cholesterol levels turned for the better also. HbA1c improved from 8.4 +/-
      1.2 to 7.5 +/- 1.0% after applying this program to patients with the HbA1c of 7%
      or higher at baseline (P = 0.010). We propose this web-based diabetic patient
      management system as a new tool for communication between health care providers
      and patients.

PMID- 15563965
TI  - Sibutramine improves fat distribution and insulin resistance, and increases serum
      adiponectin levels in Korean obese nondiabetic premenopausal women.
AB  - The aim of this study was to evaluate the effects of sibutramine on body
      composition and fat distribution, insulin resistance, and serum adiponectin
      levels in obese women. A total of 28 obese, premenopausal women (mean age, 34.5
      +/- 13.7 years; BMI, 31.00 +/- 4.10 kg/m2) was studied before and after 12-week
      course of sibutramine (10mg/day). Sibutramine treatment reduced body mass index
      (P < 0.05) and total body fat (P < 0.05). Abdominal subcutaneous and visceral fat
      areas (ASFA and AVFA) and mid-thigh low density muscle areas (LDMA) measured by
      computed-tomography decreased significantly (all, P < 0.05). Insulin resistance
      (IR) calculated from the homeostasis model assessment (HOMA) method decreased (P
      < 0.05) and serum adiponectin levels increased significantly (P < 0.05). In our
      sequential data, the changes of fasting serum insulin levels and the HOMA-IR
      scores, serum free fatty acids and triglyceride levels, serum adiponectin levels
      and the mid-thigh LDMA preceded significant changes of body weight, total body
      fat, and abdominal fat distribution, suggesting sibutramine might improve insulin
      sensitivity directly by alterations of fatty acid metabolism or secondarily by
      increasing serum adiponectin levels. Conclusively, sibutramine improved fat
      distribution and insulin resistance, and increased serum adiponectin levels in
      Korean obese nondiabetic premenopausal women.

PMID- 15563966
TI  - Meta-analysis of three diabetes population studies: association of inactive ALDH2
      genotype with maternal inheritance of diabetes.
AB  - To date, there have been three population studies that examined the association
      of mitochondrial aldehyde dehydrogenase 2 (ALDH2) genotype with inheritance of
      diabetes. Here, we summarize the results by meta-analysis. The study 1 consisted
      of 212 type 2 diabetics who did not have renal failure. The study 2 consisted of
      73 type 2 diabetics who had renal failure. The study 3 consisted of 230 type 1
      diabetics. In total, 515 subjects were examined for the association of ALDH2
      genotype with inheritance of diabetes. Out of 515 subjects, 307 (60%) had active
      ALDH2 (ALDH2*1/ALDH2*1) and 208 (40%) had inactive ALDH2 (175 had ALDH2*1/ALDH2*2
      and 33 had ALDH2*2/ALDH2*2). As for family history, 25 subjects (8.1%) in the
      active ALDH2 group had a diabetic mother, compared with 43 (20.6%) in the
      inactive ALDH2 group. Twenty-nine subjects (9.4%) in the active ALDH2 group had a
      diabetic father, compared with 14 (6.7%) in the inactive ALDH2 group. The
      percentage of diabetic mother was higher in the inactive ALDH2 group, the
      differences were statistically significant (P < 0.0001). We hence speculate that
      diabetic patients with inactive ALDH2 genotype may have underlying background of
      mitochondria etiology, thereby showing maternal trait of diabetes inheritance. In
      conclusion, meta-analysis using three diabetes population studies strongly
      confirmed the association between ALDH2 inactivity and maternal inheritance.

PMID- 15563967
TI  - Anti-hyperglycemic activity of Commelina communis L.: inhibition of alpha
      glucosidase.
AB  - Since ages, botanical substances are in use for the remedy of diabetes with
      considerable degree of success. One of the such; an extract of Commelina communis
      L. (CE-L) after decoction in water has been traditionally used for the treatment
      of diabetes in Korea. However, its action mechanism has not yet been established.
      To explore the inside of its action-mechanism, in this study, the effect of the
      aqueous extract of C. communis L. (CE-L) on the activity of alpha-glucosidase was
      evaluated in vitro and in vivo. Aqueous extract of CE-L showed inhibitory
      activity of the alpha-glucosidase in a dose-dependent manner, in vitro. CE-L also
      seems to be by and large free from exerting any cytotoxic effect at least in CHO
      K1 fibroblast and 3T3-L1 adipocyte. CE-L alleviated hyperglycemia caused by
      maltose or starch loading in normal and Streptozotocin (STZ)-induced diabetic
      mice with better efficacy than that of acarbose. In addition, prolonged
      administration of CE-L tends to normalize hyperglycemia in STZ-induced diabetic
      mice. Such results suggest that inhibitory activity of CE-L on alpha-glucosidase
      may contribute to delay in carbohydrate digestion and glucose absorption. Thus,
      CE-L has potential for use in the management of non-insulin-dependent diabetes.

PMID- 15563968
TI  - Rice bran extract prevents the elevation of plasma peroxylipid in KKAy diabetic
      mice.
AB  - Oxidative stress is now considered to be a key factor in the development of
      diabetes and its complications. In this study, we examined the anti-oxidative
      effects of a crude lipophilic rice bran extract, Ricetrienol, which contains
      alpha-tocopherol, tocotrienol and phytosterol, in obese diabetic KKAy mice. We
      used KKAy mice fed a normal diet (DM group) or a diet including 0.1% Ricetrienol
      (RT group), and non-diabetic C57BL mice (C group). After 6 weeks, body weight,
      HbA1c, plasma glucose, lipids, peroxylipid (malonedialdehyde, MDA), alpha
      tocopherol and glutathione peroxidase 1 (GPx) mRNA expression in the kidney were
      measured. At 1 week and at the end of the experimental period, urine 8
      isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were also measured. Ricetrienol
      administration did not affect hyperglycemia, body weight or hyperlipidemia.
      Plasma MDA, urine 8-isoprostane and 8-OHdG in the DM group were significantly
      increased compared with the C group and the elevation of plasma MDA was
      significantly suppressed by 0.1% Ricetrienol. GPx mRNA expression was
      significantly increased in the RT group when compared with the C group. Plasma
      alpha-tocopherol in the RT group was significantly higher than that in the DM
      group. These findings suggest that Ricetrienol exerts a protective effect against
      oxidative damage in diabetes mellitus.

PMID- 15563969
TI  - Significantly higher incidence of carotid atherosclerosis found in Japanese type
      2 diabetic patients with early nephropathy.
AB  - We have tried to evaluate the clinical incidence of carotid atherosclerosis found
      in Japanese type 2 diabetic patients with early diabetic nephropathy. 123
      diabetic patients with micro-albuminuria (group A) were investigated during 2
      week hospitalization. As a control group, 50 diabetic patients without
      nephropathy (group B) were investigated. Carotid arteries were examined by B-mode
      ultrasonography (7.5 MHz), and peripheral arterial blood flow and pressure was
      examined at the same time with Doppler ultrasonography by a single examiner.
      Fasting blood samples and 24-h urine samples were taken to analyze biochemical
      data and urinary albumin excretion rate. In group A, 77 patients were found to
      have either carotid plaque lesions or increased thickness of carotid wall. And
      this was found significantly higher than in the control group B (18 cases, P <
      0.01). To clarify the clinical risk factors for carotid atherosclerosis in
      diabetic patients with early nephropathy, 123 group A patients were divided into
      two groups with (group C, n = 76) or without carotid atherosclerosis (group D, n
      = 47) and comparative analysis was carried out. From this study, significantly
      higher incidence of carotid atherosclerosis was confirmed in the diabetic
      patients with early nephropathy. And it was suggested that the age, lipid levels,
      presence of hypertension would be important clinical risk factors for carotid
      atherosclerosis found in diabetic patients with early nephropathy.

PMID- 15563970
TI  - History of obesity as a risk factor for both carotid atherosclerosis and
      microangiopathy.
AB  - As a westernized lifestyle becomes widespread in Japan, the number of individuals
      with obesity, as well as type 2 diabetes, is rapidly increasing. In this
      investigation, we studied the prevalence of obesity and its association with the
      development of diabetic macroangiopathy and microangiopathy. The clinical records
      of 634 patients in our hospital with type 2 diabetes were surveyed. The
      relationship between obesity and diabetic retinopathy and nephropathy and
      macroangiopathy (carotid artery intima-media thickness, IMT) was examined using
      univariate and multivariate analysis. A body mass index (BMI) > or = 25 kg/m2 was
      used as the diagnostic criterion for obesity. The prevalence of obesity at the
      time of the survey was 35% and a history of obesity was reported in 70% of the
      survey population. Multiple regression analysis revealed that the maximum BMI was
      significantly correlated with IMT thickening. The prevalence of nephropathy in
      previously obese patients was significantly higher than in non-obese patients.
      The maximum BMI was significantly associated with the development of retinopathy
      and nephropathy, as shown by logistic regression analysis. This suggests that a
      history of obesity may be an important risk factor for the development of micro-
      and macroangiopathy in Japanese with type 2 diabetes.

PMID- 15563971
TI  - An implication of hypertriglyceridemia in the progression of diabetic nephropathy
      in metabolically obese, normal weight patients with type 2 diabetes mellitus in
      Korea.
AB  - This study was undertaken to investigate diverse risk factors affecting the
      progression of diabetic nephropathy (DN) by observing the changes of 24 h urinary
      albumin excretion (24 h UAE) in 90 abdominally obese, normal weight, type 2
      diabetic patients with normo- or micro-albuminuria. Patients were divided into
      three groups according to the 24h UAE; normo-, micro-, and macro-albuminuria
      group. After 4 years of follow-up, patients were divided into either progression
      or non-progression group according to the changes of 24 h UAE. About 37% of the
      normo-albuminuria group and 18% of the micro-albumiuria group were classified
      into the progression group. The initial serum creatinine levels and the initial
      and follow-up post-prandial plasma glucose levels were significantly higher in
      the progression group than in the non-progression group. Most remarkably, the
      initial and follow-up serum triglyceride (TG) levels (190 +/- 132 versus 132 +/-
      49 mg/dl and 191 +/- 124 versus 133 +/- 41 mg/dl, P < 0.01 in both) were
      significantly higher in the progression group than in the non-progression group,
      suggesting hypertriglyceridemia might be included in the progression factors of
      DN. The increases in 24-hour UAE were positively associated with the initial and
      follow-up post-prandial plasma glucose levels (P < 0.05 in both), the initial and
      follow-up serum creatinine levels (P < 0.05 in both), and the initial serum TG
      levels (P < 0.05). Whereas, insulin users or patients with retinopathy at follow
      up (P < 0.05 in both) showed more rapid progression of albuminuria, ACE
      inhibitors or acarbose (P < 0.05 in both) use turned out to protect against it.

PMID- 15563972
TI  - Prevalence and risk factors of erectile dysfunction in Japanese men with type 2
      diabetes.
AB  - This study aimed to elucidate the prevalence and clinical risk factors of
      erectile dysfunction (ED) in Japanese male diabetics. Questionnaires were
      administered to 82 male diabetics and 25 male non-diabetics (controls), to
      determine the international index of erectile function (IIEF). This index
      consists of five parts, with questions related to erectile function (EF),
      intercourse satisfaction (IS), orgasmic function (OF), sexual desire (SD), and
      overall satisfaction (OS). IIEF scores were compared between diabetics and
      controls, and were also analyzed in relation to clinical factors. Although EF,
      IS, and OF scores (physical factors) in diabetic men were significantly lower
      than those of age-matched controls, no significant differences were apparent in
      SD and OS scores (psychological factors). All patients with EF score > or = 18
      reported being able to achieve sexual intercourse, we determined the criterion
      for ED as EF < 18. The prevalence of ED in diabetics and age-matched controls was
      60% and 20%, respectively. EF score decreased with duration of diabetes and
      progression of retinopathy, proteinuria, ischemic heart disease, delayed nerve
      conduction, orthostatic intolerance, and attenuated heart rate variability. ED
      was found to be common in Japanese male diabetics. Possible influences of both
      microangiopathy and macroangiopathy on ED are suggested.

PMID- 15563973
TI  - Proposal of blood-collecting needle approach to semi-invasive method.
AB  - Many diabetic patients carry a portable self-monitoring of blood glucose (SMBG)
      analyzer in order to collect their own blood and examine their glucose levels;
      this allows them to determine such factors as insulin dose, diet and exercise to
      stay healthy. However, the test causes physical and mental stress for the
      subjects. The authors aim to develop a semi-invasive blood-collecting needle
      which does not need a power source for the pump mechanism. In this study, we
      fabricated a capillary action needle that can collect the blood sample
      automatically. A blood-collecting needle was fabricated from 25 gage sized
      medical needle (diameter of 0.5 mm, stainless steel) by cutting process, and it
      had a half-opened crevice in the tip. In order to evaluate the physical
      characteristics of the blood-collecting needle, the relationship between the size
      and suction time and/or suction volume were measured using an isotonic sodium
      chloride solution, whole rabbit blood, and whole human blood with anticoagulant.
      Next, in order to evaluate the degree of invasion, the diameters of erythema in
      auricles of rabbits were observed for 2 days using a CCD camera-type microscope.
      The mean suction time of the isotonic sodium chloride solution and the whole
      rabbit blood were 1.5 s (n = 10) and 9.0 s (n = 5), respectively. Selection of a
      suitable size of the blood-collecting needle enabled the collection of 0.1 microL
      of whole human blood in 10 s. Moreover, it was shown, by comparing the observed
      diameter of the erythema, that the invasiveness of the blood-collecting needle
      was smaller than for commercial needles of the equal diameter. It became clear
      that this fulfils the fundamental functions of a semi-invasive blood-collecting
      needle.

PMID- 15563974
TI  - Prediction of the risk of type 1 diabetes from polymorphisms in candidate genes.
AB  - Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease, in which
      pancreatic beta cells are selectively destroyed. Innate immune response is also
      important in the development of T1D. Several studies have demonstrated that HLA
      class II alleles, DQ and DR influence T1D susceptibility. Specific class I and II
      alleles are non-randomly associated with each other on an extended haplotypes,
      the typing of which provide the best risk determinants of T1D. Studying the
      haplotype in different ethnic populations will enable us to identify the exact
      polymorphisms that can trigger T1D and to develop biological tools for
      protection. With the advent of numerous candidate markers, additional loci that
      influence susceptibility to T1D have been reported. Although different studies
      have suggested that various genetic variants increase the risk, large-scale
      association studies that examine many polymorphisms simultaneously are required
      to allow reliable prediction of the genetic risk. Not only the numbers of genetic
      markers we are applying, but also the accurate phenotyping is critical in the
      success of setting-up a best-fitting model for prediction. For a better
      phenotyping, multiple autoantibodies to islet cell antigens, which may arise even
      before the clinical onset have been known as the best surrogate markers of T1D.
      However, differences in genotypes between antibody-positive individuals and T1D
      patients may indicate genetic factors, which determine progression to clinical
      disease. The ability to detect those antibody-positive individuals who will
      progress to T1D is central to prevention program.

PMID- 15563975
TI  - Prevention of type 1 diabetes: from the view point of beta cell damage.
AB  - The hallmark of immune-mediated type 1 diabetes is T cell-mediated destruction of
      the insulin-producing beta cells in the islets, which results from an imbalance
      between disease promoting factors and protective elements. The precise mechanisms
      of beta cell destruction leading to diabetes remain unclear. There are many
      molecules, including Fas ligand (FasL) and cytokines, such as IL-1, TNF-alpha and
      IFN-gamma that cause release of other cytokine-mediators that have potential to
      damage the beta cells. The beta cell-death appears to ultimately be caused by
      receptor (Fas/FasL)-mediated mechanisms and/or by secretion of cytotoxic
      molecules (e.g., granzymes, perforin). FasL-mediated beta cell damage might play
      a role in promoting insulitis and beta cell destruction in autoimmune diabetes in
      addition to toxic molecules, such as reactive oxygen species (superoxide, hydroxy
      radical, nitric oxide) or perforin. Furthermore, DNA damage in beta cells leads
      to poly (ADP-ribose) polymerase-activation which will increase NAD consumption
      and rapid depletion of NAD compromise ATP production in the cells. Nicotinamide
      inhibits poly (ADP-ribose) polymerase and reduces nitric oxide accumulation in
      the NOD pancreas and protect beta cells against radical-induced necrosis.
      Transgenic mice with beta cell specific overexpression of copper, zinc superoxide
      dismutase, or thioredoxin are resistant to autoimmune and STZ-induced diabetes.
      It is apparent that a number of different mechanisms of beta cell destruction are
      operative in type 1 diabetes. Blockage of multiple pathways, rather than a single
      pathway, of beta cell-death may, therefore be necessary to fully protect beta
      cells from destruction and thereby prevent type 1 diabetes.

PMID- 15563976
TI  - Recent advance in hepatic insulin gene therapy.
AB  - The development of type 1 diabetes results from the almost total destruction of
      insulin-producing pancreatic cells by autoimmune responses specific to cells.
      Standard insulin therapy may not maintain blood glucose concentrations within the
      relatively narrow range that occurs in the presence of normal pancreatic cells.
      We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain
      insulin analogue (SIA), which possesses biologically active insulin activity
      without enzymatic conversion, under the control of hepatocyte-specific l-type
      pyruvate kinase (LPK) promoter, which regulates SIA expression in response to
      blood glucose levels. Here, we show that SIA produced from the gene construct
      rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats
      and autoimmune diabetic mice for a prolonged time without any apparent side
      effects. This new SIA gene therapy may have potential therapeutic value for the
      cure of autoimmune diabetes in humans.

PMID- 15563977
TI  - Prevention of type 2 diabetes mellitus from the viewpoint of genetics.
AB  - The prevalence of type 2 diabetes mellitus has increased worldwide over the past
      decades. The economic and social cost associated with diabetes mellitus and its
      complications have also increased enormously. Since current methods of treating
      diabetes is inadequate, the most effective way to reduce the burden associated
      with type 2 diabetes would be to prevent diabetes itself. Current strategies to
      prevent type 2 diabetes mellitus are based on efforts to reduce insulin
      resistance and to preserve or increase pancreatic beta cell function in high risk
      individuals. Now there is substantial evidence that life style intervention or
      pharmacologic agents can reduce the development of diabetes in individuals with
      impaired glucose tolerance. However, it remains to be determined whether the
      result would be similar in other risk groups for type 2 diabetes. Although
      development of type 2 diabetes mellitus is influenced by a complex interaction
      between genetic and environmental factors, current prevention strategies do not
      reflect contribution of genetic factors. Over the past decade, many investigators
      tried to find diabetogenic genes by traditional gene discovery methods. It
      appears that multiple genes with weak effect are involved in the development of
      type 2 diabetes mellitus which makes searching diabetogenic genes more
      complicated. In addition to the completion of human genome project, new genetic
      tools to identify genetic variations and analyze gene to gene or gene to
      environmental interaction will facilitate the discovery of susceptibility genes
      for type 2 diabetes mellitus in near future. Once we could identify
      susceptibility genes and gene to environmental interaction of type 2 diabetes
      mellitus, we can clarify the role of both environmental and genetic factors in
      the development of type 2 diabetes mellitus. Moreover, we can identify people who
      can get more benefit from prevention and also can provide better and personalized
      preventive measure based on genetic information.

PMID- 15563978
TI  - Insulin secretion capacity in the development from normal glucose tolerance to
      type 2 diabetes.
AB  - We have examined the contribution of insulin secretion and insulin resistance to
      glucose intolerance in Japanese. Some indices of insulin secretion and insulin
      sensitivity based on the results of OGTT were used. The decline of insulin
      secretion capacity was significant throughout the development of glucose
      intolerance from NGT via IGT to DM. Decreased insulinogenic indices were
      conspicuous when it is compared with other types of diabetes. Slight impairment
      of insulin secretion has begun in subjects with NGT. The progression from NGT via
      isolated IGT to isolated post-challenge hyperglycemia was considered mostly due
      to the deterioration of early-phase insulin secretion. It is summarized that
      decreased insulin secretion capacity takes a definite role in the development
      from NGT to type 2 diabetes in Japan.

PMID- 15563979
TI  - Genome-wide search for susceptibility gene to diabetic nephropathy by gene-based
      SNP.
AB  - That genetic factors contribute to the onset and progression of chronic diabetic
      complications is highly convincing, but the gene or genes conferring
      susceptibility to these diseases remain to be identified. To identify genetic
      elements that might confer susceptibility to diabetic nephropathy, we performed a
      genome-wide analysis of gene-based single nucleotide polymorphisms (SNPs) in a
      large cohort of Japanese diabetic patients. In case-control association studies,
      patients with type 2 diabetes were divided into two groups, one having
      retinopathy as well as overt nephropathy and the other (the control group) with
      diabetic retinopathy but with no signs of renal involvement. Genotyping of these
      patients at more than 80,000 SNP loci suggested several distinct regions to be
      good candidates for the susceptibility to diabetic nephropathy. The results
      indicated that genome-wide search using SNP as a genetic marker is useful to
      identify the gene(s) susceptible to common diseases such as diabetic nephropathy.

PMID- 15563980
TI  - Pericytes and the prevention of diabetic retinopathy.
AB  - Diabetic retinopathy is a leading cause of blindness and one of the hallmarks of
      early diabetic retinopathy is death of pericytes. I studied the effect of
      glycated albumin (GA) on the retinal pericyte death and assessed the protective
      effects of some well-known antioxidant materials. GA produced a progressive
      cytotoxic effect in a near time and dose dependent manner. Among the antioxidant
      pretreatments, L-ascorbic acid, Trolox, produced a reduction of GA-induced
      cytototoxicity. N-Acetyl-L-cysteine showed partial effect but taurine had no
      effect on the GA-toxicity. In conclusion, I demonstrated the effect of GA on the
      retinal pericyte death and some antioxidants effectively prevented the GA-induced
      cell death in pericytes.

PMID- 15563981
TI  - Can diabetic neuropathy be prevented?
AB  - The incidence of diabetes and its complication have rapidly increased. Decreased
      quality of life and increased mortality are the major problems of people with
      diabetes. These problems are mainly caused by chronic complications. The
      incidence of diabetic neuropathy, which is one of these chronic complications,
      approaches 50% in most diabetic patients. The intensive metabolic management
      alone cannot completely prevent the development and progression of diabetic
      complications. Therefore, blocking and management of pathogenic mechanism of
      complication are required. Pathogenesis of diabetic neuropathy has multifactorial
      causes. Diabetic neuropathy is thought to occur both from direct hyperglycemia
      induced damage to the nerve parenchyma and from neuronal ischemia brought about
      indirectly by hyperglycemia-induced decreases in neurovascular flow. The effects
      of hyperglycemia get converted to neuronal dysfunction via at least three
      secondary biochemical pathways: the polyol pathway, non-enzymatic glycation of
      proteins, oxidative stress and protein kinase C, and the interactions between
      them. Because of these interactions, interference with one of these biochemical
      pathways could either worsen or attenuate the effects of the others. So, the use
      of therapeutic intervention of these pathways is inevitable and valid to prevent
      the progression of diabetic neuropathy. As yet, a satisfactory and fundamental,
      preventive, and therapeutic method is not available with us to prevent
      progression. So, we will introduce the earlier diagnostic methods of diabetic
      neuropathy and will discuss the advantages and limitations of each method.

PMID- 15563982
TI  - Prevention and treatment of macroangiopathy: focusing on oxidative stress.
AB  - Oxidative stress has been proposed to be a major cause of atherosclerosis in
      diabetes. Endothelial dysfunction, common in diabetes, is considered a
      prerequisite for atherosclerosis. We evaluated whether alpha-lipoic acid (ALA) is
      an effective treatment for oxidative stress-induced endothelial dysfunction.
      Using high resolution ultrasound techniques, we evaluated flow mediated
      vasodilation (FMD) of the brachial artery in 13 young healthy men with transient
      hypertriglyceridemia (HTG) induced by intralipid infusion and in 11
      postmenopausal type 2 diabetics before and after ALA treatment. We also measured
      superoxide anion formation in neutrophils as a maker of oxidative stress. FMD was
      decreased and superoxide anion formation was increased significantly following
      intralipid infusion in the young healthy men. ALA treatment, however, reversed
      the HTG-induced endothelial dysfunction and decreased the superoxide anion
      formation. Similarly, treatment with ALA increased FMD and decreased superoxide
      anion formation in the postmenopausal type 2 diabetics. In addition, the change
      in FMD was negatively correlated with superoxide anion formation in young healthy
      men and in postmenopausal type 2 diabetics (r = -0.54, -0.65, respectively). All
      P values were below 0.05. In conclusion, our results demonstrate that ALA
      treatment improves HTG- and diabetic-induced endothelial dysfunction, possibly
      due to the antioxidant effect of ALA.

PMID- 15563983
TI  - Association of Pro12Ala polymorphism of PPARgamma gene with insulin resistance
      and related diseases.
AB  - To clarify the contribution of the Pro12Ala polymorphism of the peroxisome
      proliferator-activated receptor gamma (PPARgamma) gene to susceptibility to
      insulin resistance and related diseases, 505 unrelated Japanese subjects were
      investigated, including 175 normotensive non-diabetic (NN) subjects, 125
      normotensive diabetic (ND) subjects, 102 hypertensive non-diabetic (HN) subjects,
      and 103 hypertensive diabetic (HD) subjects. Ala phenotype frequency was lowest
      in patients with both type 2 diabetes and hypertension (3.9% in HD group),
      followed by patients with either one of these conditions (5.6% in ND group, 7.8%
      in HN group), and highest in subjects without these conditions (9.7% in NN
      group). When stratified by hypertensive status, the Ala phenotype was negatively
      associated with diabetes, giving an odds ratio of 0.53 (95% confidence interval:
      0.25-1.09). In contrast, when stratified by diabetic status, the odds ratio of
      the Ala phenotype for hypertension was 0.75 (95% confidence interval: 0.37-1.54).
      In non-diabetic hypertensive subjects, glucose and insulin levels during oral
      glucose tolerance test as well as M-value estimated by glucose-clamp test were
      not significantly different according to the genotype. The data suggest a
      contribution of the Pro12Ala polymorphism of PPARgamma to genetic susceptibility
      to type 2 diabetes mellitus and hypertension, but not to insulin sensitivity in
      hypertensive subjects.

PMID- 15563984
TI  - Enhancing effect of taurine on glucose response in UCP2-overexpressing beta
      cells.
AB  - Uncoupling protein 2 (UCP2) is up-regulated in pancreatic beta cells when exposed
      to long-term high glucose or free fatty acids, which results in impaired glucose
      induced insulin secretion (GIIS). We have evaluated whether taurine pretreatment
      can restore impaired GIIS of beta cells overexpressing UCP2 by adenovirus (Ad)
      mediated transfection technique. In Ad-Null control cells, externally applied
      glucose (10 mM) inhibited ATP-sensitive potassium (K(ATP)) channel activity even
      in the presence of 300 microM diazoxide. In Ad-UCP2 cells, however, glucose
      failed to inhibit K(ATP) channel activity; despite the response of K(ATP) channel
      itself to glibenclamide was normal. The glucose-stimulated increase of cytosolic
      Ca2+ concentration ([Ca2+]c) and insulin secretion was also diminished (P <
      0.05). When taurine (3 mM) was pretreated for 24 h, the glucose responses of Ad
      UCP2 cells were remarkably restored. The effect of taurine was, however, blocked
      by CCCP (carbonyl cyanide p-chlorophenylhydrazone; 2 microM), a mitochondrial
      Ca2+ uniporter inhibitor. These results suggest that taurine restores impaired
      GIIS in Ad-UCP2 cells, at least partially, by acting on the mechanism for Ca2+
      sequestration into the mitochondrial matrix.

PMID- 15563985
TI  - Sulfonylurea and non-sulfonylurea hypoglycemic agents: pharmachological
      properties and tissue selectivity.
AB  - ATP-sensitive K+ (K(ATP)) channels play many important roles in cellular
      functions, including control of membrane excitability of skeletal muscle and
      neurons, K+ recycling in renal epithelia, cytoprotection in cardiac ischemia, and
      insulin secretion from pancreatic beta-cells. K(ATP) channels are composed of
      pore-forming inwardly rectifying potassium channel (Kir6.2 or Kir6.1) subunits
      and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits. Kir6.2 or Kir6.1
      subunits conjoined with a SUR subunit constitute the various tissue-specific
      K(ATP) channels with distinct pharmacological properties. Both sulfonylureas and
      non-sulfonylurea hypoglycemic agents are used in treatment of type 2 diabetes
      mellitus. While the sulfonylurea receptor (SUR) is the target molecule of all of
      these hypoglycemic agents, the binding sites differ according to the moiety
      containing in the agent, and alter the pharmachological properties. In addition,
      chronic exposure of pancreatic beta-cells to the various agents affects the agent
      specific sensitivities differently. Here we distinguish differences in
      pharmacological profile among the various hypoglycemic agents that reflect their
      chemical composition. We also suggest possible risk in the use of certain
      hypoglycemic agents in patients with ischemic heart disease.

PMID- 15563986
TI  - TNFalpha reduces the expression of peroxisome proliferator-activated receptor
      gamma (PPARgamma) via the production of ceramide and activation of atypical PKC.
AB  - Although tumor necrosis factor alpha (TNFalpha) decreases the expression of
      peroxisome proliferator-activated receptor gamma (PPARgamma), its mechanism is
      not understood. We evaluated the effect of ceramide, the second messenger of
      TNFalpha, on the expression of PPARgamma in primary cultured adipocytes.
      PPARgamma mRNA and aP2 mRNA levels were measured with real-time PCR. The
      PPARgamma protein level was measured with immunoblot. C6- and C2-ceramide, but
      not dihydroC6-ceramide, reduced the expression of PPARgamma in a time and
      concentration dependent manner. The application of 1 microM C6-ceramide for 36 h
      reduced PPARgamma mRNA level, aP2 mRNA level, and PPARgamma protein level to
      56.3%, 80.4% and 62.1%, respectively. Since ceramide is known to activate
      atypical PKC, we also studied the role of atypical PKC on the PPARgamma reducing
      effect. Overexpression of wild type PKCzeta magnified and accelerated the effect
      of TNFalpha and C6-ceramide on PPARgamma mRNA levels, whereas overexpression of
      dominant negative PKCzeta abolished the effect. We also found that the
      overexpression of constitutive active PKCzeta reduced PPARgamma mRNA level, aP2
      mRNA level, and PPARgamma protein level to 61.4%, 70.3% and 81.6%, respectively.
      Furthermore, TNFalpha activated nuclear factor-kappaB (NF-kappaB), known as a
      downstream effector of PKCzeta to 256.6%, which was enhanced with overexpression
      of wild-type PKCzeta. On the other hand, treatment with phorbol 12-myristate 13
      acetate, another activator of NF-kappaB, also reduced the expression of PPARgamma
      to 57.8%. These results indicate that the reducing effect of TNFalpha is mediated
      through ceramide, atypical PKC and NF-kappaB pathway.

PMID- 15563987
TI  - Idd1 and Idd3 are necessary but not sufficient for development of type 1 diabetes
      in NOD mouse.
AB  - Type 1 diabetes in the NOD mouse is under polygenic control, with a major
      susceptibility gene, Idd1, in the major histocompatibility complex (MHC). To
      investigate the contribution of the NOD MHC to type 1 diabetes susceptibility, a
      B6.NOD-H-2 congenic strain, in which the NOD MHC was introgressed onto the
      genetic background of the C57BL/6 strain, was established. Despite possession of
      the diabetogenic MHC from the NOD mouse, none of the B6.NOD-H-2 mice developed
      type 1 diabetes, indicating that the NOD MHC alone is not sufficient for type 1
      diabetes and that non-MHC genes are also necessary. One of the strongest non-MHC
      genes is Idd3, and Il2 which encodes interleukin 2, is a candidate gene for Idd3.
      To test whether a combination of the NOD MHC with the NOD allele of Il2 is
      sufficient for type 1 diabetes, B6.NOD-H-2 mice were crossed with C3H mice, which
      possess the NOD allele at Il2, and F2 mice homozygous for NOD alleles at both the
      MHC and Il2 were produced. None of the F2 mice developed type 1 diabetes,
      suggesting that NOD alleles at MHC (Idd1) and Il2 (Idd3) are not sufficient for
      type 1 diabetes in the NOD mouse.

PMID- 15563988
TI  - Common genetic basis between type 1 and type 2 diabetes mellitus indicated by
      interview-based assessment of family history.
AB  - To investigate the intrafamilial clustering of type 1 and type 2 diabetes, an
      interview-based assessment of family history of diabetes was conducted.
      Outpatients with either type 1 (n = 23) or type 2 diabetes (n = 124), and non
      diabetic subjects (n = 118) received an interview regarding the diabetic status
      of each of their family members. In patients with type 1 diabetes, 22% (5 out of
      23) had a parental history of diabetes, and diabetes in these 5 parents was
      assessed as type 2 diabetes mellitus. The prevalence of parental diabetes in the
      type 1 diabetic probands (22%) was significantly higher (P < 0.05) than that in
      non-diabetic probands (7%, 8 out of 118). In probands with type 2 diabetes, the
      prevalence of parental diabetes was 39% (48 out of 124), which was significantly
      higher (P < 0.0005) than that in the non-diabetic probands (7%). In the type 2
      diabetic probands, no significant difference was noted in the prevalence between
      paternal (19%, 23 out of 124) and maternal diabetes (23%, 28 out of 124),
      suggesting no preferential inheritance of maternal diabetes in this population.
      The present interview-based assessment of family history of diabetes suggested a
      common genetic basis between type 1 and type 2 diabetes.

PMID- 15563989
TI  - Dexamethasone suppresses the expansion and transdifferentiation of transplanted
      porcine neonatal pancreas cell clusters (NPCCs) into beta-cells in normal nude
      mice.
AB  - OBJECTIVES: This study was performed to investigate the effect of dexamethasone
      on the expansion and transdifferentiation of transplanted neonatal pancreas cell
      clusters (NPCCs) in vivo. METHODS: Porcine NPCCs were generated from 1 to 3-day
      old neonatal pigs. After transplantation (Tx) of 4000 islet equivalents (IEqs) of
      NPCCs beneath the renal subcapsular space of normoglycemic nude mice,
      dexamethasone (Dx, 1 mg/kg) or vehicles were injected daily. Intraperitoneal
      glucose tolerance testing (ip-GTT) was performed at 4 weeks (n = 4) and 10 weeks
      (n = 7) after Tx. After harvesting the grafts, total graft and beta-cell graft
      mass were determined by morphometric analysis. RESULTS: Although the mean value
      of AUCg was elevated in the Dx-treated group at 10 weeks after Tx, the glucose
      levels of all the animals by ip-GTT were within the normal range. At 10 weeks
      after Tx, the relative volume, absolute mass of beta-cells in the graft, and
      total graft mass were significantly lower in the Dx-treated group (relative
      volume of beta-cells: 22.0% versus 35.3%, P < 0.05; beta-cells mass: 1.0 +/- 1.2
      mg versus 2.2 +/- 5.6 mg, P < 0.05, total graft mass: 4.4 +/- 5.4 mg versus 6.3
      +/- 1.3 mg, P < 0.05, Dx-treated versus control), but there was no difference at
      4 weeks. Morphologically prominent cystic structures were observed in the Dx
      group at 10 weeks. CONCLUSION: Our results suggest that dexamethasone suppresses
      the expansion and transdifferentiation of transplanted porcine NPCCs into beta
      cells in normal nude mice.

PMID- 15563990
TI  - Healthcare reform implementation: stakeholders and their roles-the Israeli
      experience.
AB  - In early 1995, Israel implemented a healthcare reform. The course of any such
      reform depends largely on the strengths and interests of different stakeholders
      in the health system and their roles during the implementation phase. This paper
      discusses the roles of stakeholders in the recent Israeli healthcare reform,
      analyzes their motives, and describes their impact on the course of the reform.
      In retrospect, the Israeli healthcare reform had a profound effect on the
      country's overall healthcare environment and involved significant social,
      cultural, and financial changes and advancements. However, imbalances among
      stakeholders in the health system caused several aspects of the reform to stray
      from the original plan. Thus, in the first few years after the reform only first
      steps were taken toward the fulfillment of the vision of the reform, an equitable
      healthcare system that meets the health needs and welfare of the population from
      cradle to grave. A study of the stakeholders may further our understanding of the
      process of health-reform implementation.

PMID- 15563991
TI  - The macro determinants of health expenditure in the United States and Canada:
      assessing the impact of income, age distribution and time.
AB  - This paper examines the determinants of real per capita health expenditures in
      order to assess the impact of age distribution, income and time using American
      state-level data for the period 1980-1998 and Canadian province-level data for
      the period 1975-2000. Ageing population distributions and income explain a
      relatively small portion of health expenditures when the impact of time effects,
      which is a partial proxy for technological change, is controlled for. However,
      the impact of age is of more concern given that cost increases are concentrated
      in the last few years of life and there may be cohort effects as the "Baby-Boom"
      generation ages. There is an urgent need to better understand the exact
      mechanisms driving health expenditure increases given that time accounts for
      approximately two-thirds of health expenditure increases and that its effect is
      non-linear.

PMID- 15563992
TI  - A cost-effectiveness analysis of domestic radon remediation in four primary care
      trusts located in Northamptonshire, UK.
AB  - The paper considers how primary care trusts (PCTs), which are relatively new
      organisations in the UK health service, might respond to the health hazards
      associated with radon in domestic properties. To this end, the cost-effectiveness
      of radon remediation programmes in four primary care trusts is calculated and
      compared with those of other interventions that can avert and treat lung cancer.
      The results suggest remediation programmes in the primary care trusts are cost
      effective on various criteria. Policy recommendations that follow for the primary
      care trusts include encouraging remediation among their populations and
      identifying those most at risk from radon's effects.

PMID- 15563993
TI  - The consistency of panelists' appropriateness ratings: do experts produce
      clinically logical scores for rectal cancer treatment?
AB  - OBJECTIVE: To quantify the clinical consistency of expert panelists' ratings of
      appropriateness of pre-operative and post-operative chemotherapy plus radiation
      for rectal cancer. METHODS: A panel of nine physicians (two surgeons, four
      medical oncologists, three radiation oncologists) rated the appropriateness of
      providing pre-operative and post-operative treatments for rectal cancer,
      utilizing a modified-Delphi (RAND/UCLA) approach. Clinical scenarios were paired
      so that each component of a pair differed by only one clinical feature (e.g.
      tumor stage). A pair of appropriateness ratings was defined as inconsistent when
      the clinical scenario that should have had the higher (or at least equal)
      appropriateness rating was given a lower rating. The rate of inconsistency was
      analyzed for panelists' ratings of pre- and post-operative chemotherapy plus
      radiation. RESULTS: The final panel rating was inconsistent for 1.19% of pre
      operative scenario pairs, and 0.77% of post-operative scenario pairs. Using the
      conventional RAND/UCLA definition of appropriateness, the magnitude of the
      inconsistency would produce inconsistent appropriateness ratings in 0.43% of pre
      operative and 0.11% of post-operative scenario pairs. There was significant
      variation in the rate of inconsistency among individual panelists' final ratings
      of both pre-operative (range: 0.43-5.17%, P < 0.001) and post-operative (range:
      0.51-2.34%, P < 0.001) scenarios. Panelists' overall average rate of
      inconsistency improved significantly after the panel meeting and discussion (from
      5.62 to 2.25% for pre-operative scenarios, and from 1.47 to 1.24% for post
      operative scenarios, both P < 0.05). There was no clear difference between
      specialty groups. Inconsistency was related to the structure of the rating
      manual: in the second round there were no inconsistent ratings when scenario
      pairs occurred on the same page of the manual. CONCLUSIONS: The RAND/UCLA
      appropriateness method can produce ratings for cancer treatment that are highly
      clinically consistent. Modifications to the structure of rating manuals to
      facilitate direct assessment of consistency at the time of rating may reduce
      inconsistency further.

PMID- 15563994
TI  - Health care seeking behaviour and utilisation of traditional healers in Kalabo,
      Zambia.
AB  - OBJECTIVE: To identify traditional healers in the catchment area of Kalabo
      District Hospital and to investigate determinants which play a role in the choice
      between different health care options, and to explore possibilities for
      increasing co-operation between the District Hospital and traditional healers.
      METHODS: In a cross-sectional comparative and descriptive study, a combination of
      both quantitative and qualitative methods was used. A total of 12 health workers,
      13 traditional healers and 100 community representatives were interviewed, using
      (semi)-structured questionnaires. A focus group discussion was held with 12
      traditional healers. RESULTS: This study shows that all respondents are willing
      to visit the hospital if they fall ill in future, and 88% of the respondents will
      visit a traditional healer. More women than men visit traditional healers, but
      the men who do visit them, do so more frequently. Level of education is not an
      important determinant. Increasing age leads to more frequent visits to both the
      hospital and traditional healers. Almost half of the respondents (49%) only have
      to walk less than 30 min to a traditional healer, but the hospital is the same
      distance for only 34% of the respondents. Waiting time turned out to be an
      important factor: in the hospital, 48% of the respondents are not helped within
      time, and only 28% are not helped in time by the traditional healer. Demon
      possession, mbaci, kanono and infertility are typical health problems for which
      people visit a traditional healer. The cost of treatment from a traditional
      healer is usually one cow, but only if the patient is cured. Satisfaction was
      measured at 89% after hospital treatment, and 74% after treatment from a
      traditional healer. If dissatisfied with the traditional healer, 86% would
      consider attending the hospital.

PMID- 15563995
TI  - Why neoliberal health reforms have failed in Latin America.
AB  - This paper reviews Latin American neoliberal health reforms sponsored by the IMF
      and the World Bank, and analyzes the impact on the region of decentralization and
      privatization, the two basic components of the reforms. The second part of the
      paper examines in some detail the Chilean and Colombian reforms, the two
      countries that have implemented closely the principles of the neoliberal reform.
      The two case studies confirm that neoliberal reforms do not improve quality of
      care, equity, and efficiency. In the discussion the authors identify the
      beneficiaries of the reforms: transnational corporations, consultant firms, and
      the World Bank's staff. The recognition of the beneficiaries helps to explain
      some of the reasons behind the Word Bank continuing pressures to implement
      neoliberal health reforms in spite the growing evidence of their failures.

PMID- 15563996
TI  - Postpolio syndrome: a challenge to the health-care system.
AB  - The practical eradication of poliomyelitis in industrialized countries marks one
      of the most important achievements of world health policy. Yet, disability
      induced by polio not only continues to exist among survivors with paralytic
      sequelae, but may also be further accentuated in a considerable number of
      affected subjects by the development of postpolio syndrome (PPS). PPS aggravates
      the motor sequelae already present in such subjects and reduces their functional
      capacity to the point where it affects their activities of daily living and
      worsens their quality of life. Inasmuch as development of PPS questions the
      concept of poliomyelitis as a static disease it poses a challenge not only to
      health professionals but also to policy-makers tasked with providing the
      necessary health-care measures and appropriate resources. This study sought to
      review research on this syndrome and to draw up some recommendations that might
      prove useful to the health authorities for decision-making purposes.

PMID- 15563997
TI  - Quality based social insurance coverage and payment of the application of a high
      cost medical therapy: the case of spinal cord stimulation for chronic non
      oncologic pain in The Netherlands.
AB  - This article describes a project in which a national continuous quality
      improvement system and a payment scheme were explicitly linked, while introducing
      an expensive treatment (Spinal Cord Stimulation (SCS)) in the social health
      insurance benefit package, in The Netherlands. By linking a national CQI system
      and a payment scheme in a conditional financing policy a steering instrument for
      future control of the quality of neuromodulation treatment through SCS is
      created.

PMID- 15563998
TI  - "Interaction" and research utilisation in health policies and programs: does it
      work?
AB  - The objective of this study was to assess if interaction between users and
      producers of research is associated with a greater level of adoption of research
      findings in the design and delivery of health care programs. Responses to the
      dissemination of a research report on breast cancer prevention were compared
      between two groups of public health units in Ontario, Canada. Although all public
      health units received the report, only a subset of units was involved in the
      development of the report, while others were not. Research utilisation was
      conceptualized in terms of stages, including reading the report, information
      processing, and application of findings for public health units' policies and
      programs. Using a multi-case study design, three units that contributed to the
      report's production (the interacting units) were compared with three units were
      not involved in producing the report (the comparison units) on the basis of
      research utilisation. Data collection involved group interviews and document
      review. Results demonstrated that interacting units had a greater understanding
      of the report's analysis and attached greater value to the report. However,
      interaction was not associated with greater levels of utilisation in terms of
      application. Both interacting and comparison units used the research findings to
      confirm that their on-going program activities were consistent with the research
      findings, and to compare their program performance relative to other units. In
      conclusion, interaction influenced the understanding of the research, and intent
      to use the research findings, but applied use was independent of interaction
      between producers and users of research.

PMID- 15563999
TI  - Winning ways.

PMID- 15564000
TI  - Handwashing in healthcare workers: accessibility of sink location does not
      improve compliance.
AB  - In spite of its importance, handwashing frequency in healthcare workers is
      generally low. The rebuilding and relocation of an 800-bed tertiary referral
      hospital on the same campus allowed assessment of the impact of easy
      accessibility to sinks on handwashing compliance. The new hospital design ensured
      that no clinical activity could occur more than 5 m (usually much less) from a
      sink. In the old hospital, clinical staff were often up to 30 m from a sink.
      Covert observation of nursing staff was undertaken in intensive care, infectious
      diseases, internal medicine and urology wards, over a total of 24 h during three
      consecutive days, two months before and one and 10 months after relocation to the
      new hospital. In all areas, handwashing compliance was greater before than after
      patient contact. Initial increases (9-24%) in after-patient contact handwashing
      frequency following patient contact were demonstrated in units of both high and
      low clinical care activity one month after relocation. However, no sustained
      clinically significant improvement could be demonstrated nine months later. Glove
      use was shown to diminish compliance with handwashing protocols by as much as
      25%. Improved accessibility to sinks does not lead to an improvement in
      healthcare workers' handwashing compliance.

PMID- 15564001
TI  - Antibiotic susceptibility and REP-PCR fingerprints of Acinetobacter spp. isolated
      from a hospital ten years apart.
AB  - The antibiotic susceptibility profiles and the repetitive extragenic palindromic
      sequence-based polymerase chain reaction (REP-PCR)-determined genotypes of 109
      Acinetobacter strains collected from the University Malaya Medical Center (UMMC),
      Kuala Lumpur, Malaysia, in 1987 (N=21) and 1996-1998 (N=88) were established.
      Twelve antibiotic susceptibility profiles of antibiotics used at the UMMC were
      obtained. In descending order of effectiveness, imipenem, amikacin and
      ciprofloxacin were the most effective against the Acinetobacter strains. Compared
      with 1987 isolates, the isolates obtained in 1996-1998 had decreased
      susceptibility to these antibiotics and were tolerant to the antibiotics up to an
      MIC90 of > or =256 mg/L. REP-PCR DNA fingerprints of all the isolates revealed
      the presence of four Acinetobacter spp. lineages; 92% of all the isolates
      belonged to two dominant lineages (genotypes 1 and 4). Genotype 4 isolates
      predominant in 1987 showed increased resistance and antibiotic tolerance to
      imipenem, amikacin and ciprofloxacin compared with the 1996-1998 isolates. In
      contrast, genotype 1 isolates from 1996-1998 were mainly sensitive to these
      antibiotics. These findings demonstrate the presence of at least two independent
      Acinetobacter spp. lineages in the same hospital, and suggest the possibility
      that genotype 4 Acinetobacter spp. acquired the resistance phenotype in situ,
      whereas most of the genotype 1 isolates were probably introduced to the hospital
      in recent years.

PMID- 15564002
TI  - Detection of Mycobacterium tuberculosis complex by PCR in hospital air samples.
AB  - Tuberculosis remains a health problem in many developed countries. After the
      development of a sedimentation method, a semi-quantitative approach for
      bioaerosol monitoring of Mycobacterium tuberculosis based on polymerase chain
      reaction (PCR) was adapted for direct detection in air. Bovine serum albumin was
      added to override airborne environmental particle PCR inhibitors. The method gave
      positive results in hospital rooms where tubercular pneumonia patients were
      hospitalized during the first days after their diagnosis.

PMID- 15564003
TI  - Detection and molecular characterization of a gentamicin-susceptible, methicillin
      resistant Staphylococcus aureus (MRSA) clone in Rio de Janeiro that resembles the
      New York/Japanese clone.
AB  - Staphylococcus aureus is the leading cause of hospital-acquired infections in
      many countries, and multiple factors contribute to the ability of these bacteria
      to disseminate and spread in hospitals. In Brazil it has been demonstrated that a
      multiresistant methicillin-resistant S. aureus clone, the so-called Brazilian
      epidemic clone, is widespread geographically. This clone was first detected in
      1992 in Brazil, and recently from many other countries within South America,
      Europe and Asia. The study describes the detection of a gentamicin-susceptible
      heterogeneous MRSA clone that resembles another MRSA clone widely spread in US
      and Japanese hospitals, and supports the premise that the detection of
      heterogeneous MRSA isolates by some recommended methods is a challenging task
      that may, occasionally, result in MRSA misidentification.

PMID- 15564004
TI  - Long-term features of norovirus gastroenteritis in the elderly.
AB  - Noroviruses are important pathogens in both sporadic cases and outbreaks of
      gastroenteritis in humans. Noroviruses can affect individuals of all ages in a
      variety of settings, but are a particularly important cause of gastroenteritis in
      aged-care facilities. The relationship between clinical symptoms and norovirus
      excretion and the possible role of asymptomatic carriage of norovirus in the
      elderly are poorly understood. This study examined symptoms and norovirus
      excretion in elderly individuals associated with a norovirus outbreak in an aged
      care facility. Ten individuals aged 79-94 years were recruited for the study.
      Nine were symptomatic and one was an asymptomatic contact who subsequently
      developed gastroenteritis. The 10 participants were interviewed regarding their
      clinical symptoms between two and six times over a three-week study period. One
      or more sequential faecal samples were collected from all participants over the
      same period and tested by reverse transcription-polymerase chain reaction for the
      presence of norovirus. Norovirus was detected in faecal samples from all 10 study
      participants and was commonly detected in formed stools. In the nine symptomatic
      participants, acute symptoms such as diarrhoea and vomiting had largely resolved
      by the third or fourth day of illness, but non-specific symptoms such as
      headache, thirst and vertigo could persist for as long as 19 days. Both acute and
      non-specific symptoms appeared to resolve and recur in some participants. The
      median excretion time for norovirus was 8.6 days (range 2-15 days) in symptomatic
      participants (N=5). There was no general relationship between the duration of
      norovirus excretion and the duration of either acute or non-specific symptoms. A
      faecal sample collected from the asymptomatic contact the day before
      gastroenteritis symptoms began was positive for norovirus, demonstrating
      prodromal excretion of norovirus. The results of this study indicate that
      infection control guidelines should consider both long-term excretion and
      prodromal excretion of norovirus, and the possibility that formed stools can
      contain norovirus. Furthermore, the care of elderly individuals recovering from a
      norovirus infection should take long-term non-specific clinical symptoms into
      account.

PMID- 15564005
TI  - Knowledge, practice and attitude towards standard isolation precautions in
      Iranian medical students.
AB  - Medical students are at high risk of being exposed to blood-borne pathogens. The
      aim of this study was to identify the levels of knowledge, attitude and practice
      of medical students regarding standard isolation precautions in Iran. A
      questionnaire was filled out by 468 medical students in their fifth to seventh
      year of study. Their mean knowledge, attitude and practice levels of standard
      isolation precautions were 6.1+/-1.5 (maximum possible score 9), 32.3+/-3.5 (out
      of 45), and 2.3+/-1.6 (out of 9), respectively. Statistically significant
      positive correlations were observed between knowledge and attitude, knowledge and
      practice, and practice and attitude. Ninety percent of medical students in Shiraz
      had received no education of standard isolation precautions, and 75% of
      respondents wanted more education on standard isolation precautions. Education on
      infection control issues should not only be focused on healthcare workers, but
      should also include medical students.

PMID- 15564006
TI  - Antibiotics on urethral catheter withdrawal: a hit and miss affair.
AB  - Globally, millions of patients undergo urethral catheterization every year. Our
      objective was to study the current use of prophylactic antibiotics on urinary
      catheter withdrawal. A questionnaire (N = 300) was sent to healthcare
      professionals involved in the management of patients with urinary catheters
      (consultant microbiologists, infection control nurses, consultant urologists,
      specialist nurses in urology, continence advisers and consultants in the care of
      older people). The questionnaire asked about their use of prophylactic
      antibiotics on the withdrawal of a urethral catheter. Sixty percent of healthcare
      professionals advocated the use of antibiotics for either all or selected groups
      of patients. The remainder did not. The use of prophylactic antibiotics varied
      among different groups. Of the healthcare professionals who used antibiotics, the
      majority cited more than one reason for their use (prevent bacteraemia, avoid an
      infection in a prosthesis or urinary tract infection). The course and type of
      antibiotic used varied. Our study has shown diversity in practice that is of
      concern. At present, just over one-half of patients with urinary catheters are
      being given antibiotics, although there is no evidence to suggest that such an
      intervention confers any benefit. If benefits do not exist, these patients are
      being exposed to the harm of antibiotics and providers are incurring costs
      unnecessarily. A formal trial to address this issue is urgently needed.

PMID- 15564007
TI  - The future of the UK infection control doctor: report of a one-day Association of
      Medical Microbiologists organized workshop.

PMID- 15564008
TI  - Rubella immunity and immunization of male hospital personnel.

PMID- 15564009
TI  - . . . and where did your baggage end up?

PMID- 15564012
TI  - Idiopathic pulmonary fibrosis: current trends in management.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic scarring illness limited to the
      lung and characterized by progressive dyspnea, restrictive pulmonary physiology,
      and radiographic diffuse lung disease. During the past few years, significant
      progress has been made, particularly in diagnosis: a stricter case definition has
      been outlined by consensus among international experts. Insights into the
      pathophysiology have revealed novel areas for therapeutic intervention. These
      advances have helped clarify many important diagnostic and therapeutic issues in
      this disease. An effective treatment regimen is yet to be determined. Significant
      new insights in the natural course and monitoring disease course have provided
      use of appropriate endpoints to test the safety and efficacy of new treatment
      regimens. Several multicenter clinical trials are underway and several more are
      being planned. It is hoped that ongoing molecular genetic studies and results of
      clinical trials will improve outcome of patients and families affected with this
      disease in the near future.

PMID- 15564013
TI  - The role of bronchoalveolar lavage in interstitial lung disease.
AB  - Considerable progress has been made in understanding the similarities and
      differences among the forms of the interstitial lung diseases (ILDs),
      particularly the forms of idiopathic interstitial pneumonia, now recognized as
      distinct clinicopathologic entities. Lung parenchymal evaluation by high
      resolution CT scanning of the chest may provide images that are virtually
      diagnostic of certain forms of ILD, but other testing, including bronchoalveolar
      lavage (BAL) and lung biopsy, may be required for accurate diagnosis. The
      differential diagnosis of these disorders rests on the clinician's interpretation
      of the clinical presentation and physical examination findings, pulmonary
      function testing, radiographic imaging, and, if required, sampling of lung
      tissue. This discussion examines the usefulness of BAL in the diagnosis of
      specific forms of ILD.

PMID- 15564014
TI  - Imaging of the chest: idiopathic interstitial pneumonia.
AB  - This article continues the discussion of imaging of interstitial lung diseases
      that was begun in the last issue. We summarize the typical imaging features of
      idiopathic interstitial pneumonias, emphasizing high-resolution CT. Based on the
      American Thoracic Society classification system, the idiopathic interstitial
      pneumonias are discussed under these sections: idiopathic pulmonary
      fibrosis/usual interstitial pneumonitis, nonspecific interstitial pneumonitis,
      cryptogenic organizing pneumonia, desquamative interstitial pneumonitis,
      respiratory bronchiolitis-associated interstitial lung disease, acute
      interstitial pneumonitis, and lymphoid interstitial pneumonitis.

PMID- 15564015
TI  - Pathology of interstitial lung disease.
AB  - A large and diverse group of pathologic conditions manifests clinically and
      radiologically as diffuse parenchymal lung disease. Diffuse interstitial lung
      diseases (ILDs) encompass mainly inflammatory processes that involve the
      structural elements of this organ. Some ILDs are caused by infections, but most
      are the result of immunologic, environmental, or toxic mechanisms. Currently,
      less morbid sampling techniques have increased dramatically the probability that
      pulmonologists will be faced with establishing a specific and clinically relevant
      diagnosis using surgical lung biopsy material. Most of the concepts presented in
      this article have been established using this type of specimen. In the early
      years of surgical lung biopsy, a small number of diffuse inflammatory conditions
      came to light that exclusively involved the lungs and did not seem to be caused
      by infection, toxin, sarcoidosis, pneumoconiosis, or neoplasm. In this article,
      these idiopathic disorders are discussed in the context of their dominant
      pathologic findings rather than presented as a separate group of entities.

PMID- 15564016
TI  - Nonspecific interstitial pneumonia: a real clinical entity?
AB  - Based on the current multidisciplinary classification of idiopathic interstitial
      pneumonia (IIP) organized by ATS/ERS, nonspecific interstitial pneumonia (NSIP)
      is considered as one type of IIP. An incidence of idiopathic NSIP is relatively
      small and possesses clinical features that are different than idiopathic
      pulmonary fibrosis (IPF) and usual interstitial pneumonia (UIP). Because there is
      little evidence of a long-term prognosis in patients with NSIP, some of them have
      an unfavorable prognosis similar to IPF/UIP. We review the significance of
      prognostic factors that have been reported in patients with IPF/UIP by applying
      them to patients with NSIP. The association with collagen vascular diseases
      focuses on etiologic background. Finally, the article discusses whether NSIP
      could be an early lesion of UIP based on the reported evidence and our own
      professional experiences.

PMID- 15564017
TI  - Respiratory bronchiolitis associated with interstitial lung disease and
      desquamative interstitial pneumonia.
AB  - This article explores issues of the diagnosis and management of respiratory
      bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease,
      and desquamative interstitial pneumonia. These three diseases have common and
      overlapping features and sometimes are viewed as a continuum of smoking-induced
      disease, rather than as distinct and separate entities.

PMID- 15564018
TI  - Cryptogenic organizing pneumonia.
AB  - Cryptogenic organizing pneumonia is a rare, distinct disorder that is
      sufficiently different from the other diseases in the group of idiopathic
      interstitial pneumonias to be designated as a separate entity. In its most
      typical presentation, it is characterized by dyspnea and cough, with multiple
      patchy alveolar opacities on pulmonary imaging. Definite diagnosis is obtained by
      the finding of buds of granulation tissue in the distal airspaces at lung biopsy.
      No cause (as infection, drug reaction, or associated disease as connective tissue
      disease) is found. Corticosteroid treatment is rapidly effective, but relapses
      are common on reducing or stopping treatment.

PMID- 15564019
TI  - Acute interstitial pneumonia.
AB  - The idiopathic interstitial pneumonias have unknown etiology and are
      characterized by diffuse parenchymal lung involvement and the potential to
      develop pulmonary fibrosis. Most portend a reduction in life expectancy due, in
      part, to the absence of effective therapies. The symptoms of idiopathic
      interstitial pneumonia develop insidiously. In contradistinction, acute
      interstitial pneumonia (AIP, also known as acute interstitial pneumonitis) is
      unique in that it has a very rapid to fulminant onset, leading to early
      hospitalization and a high initial case fatality ratio but, potentially, a more
      favorable long-term prognosis for survivors. Despite its contemporary description
      nearly 20 years ago, knowledge of this disease has increased little. This review
      focuses on AIP and its current place among the idiopathic interstitial
      pneumonias.

PMID- 15564020
TI  - Idiopathic pulmonary fibrosis: new insights into pathogenesis.
AB  - The combination of the unique pathologic features of usual interstitial pneumonia
      (UIP) on biopsy, the progressive clinical course, and resistance to anti
      inflammatory therapy constitutes the cardinal manifestations of what is termed
      idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia, and it has led
      to recent suggestions that new therapies should be directed at regulating
      fibroblast functions rather than targeting the inflammatory response. The
      observation that "early" UIP looks like "late" UIP but there is less of it has
      been largely responsible for re-evaluation of the paradigm that IPF is the result
      of uncontrolled lung inflammation. This article highlights aspects of current
      thoughts on pathogenesis of IFP and expands on recent reviews.

PMID- 15564021
TI  - Medical treatment for pulmonary fibrosis: current trends, concepts, and
      prospects.
AB  - A diagnosis of idiopathic pulmonary fibrosis (IPF) carries a poor prognosis, with
      our currently available therapies offering little clinical benefit.
      Unfortunately, recent major advances in our understanding of the clinical and
      biologic features of this disease have not been matched by similar advances in
      treatment. This is likely because of the complex cascade of biologic and
      pathobiologic events that occurs in IPF. The necessary, and desperately needed,
      next generation of therapies, focused on specific molecular targets thought to
      play pivotal roles in the development and progression of fibrosis, are under
      active investigation.

PMID- 15564022
TI  - Lung transplantation for interstitial lung disease.
AB  - Lung transplantation remains the only therapeutic option shown to improve
      survival for many end-stage interstitial lung diseases. Although idiopathic
      pulmonary fibrosis is the most common indication, transplantation has been
      performed for many other diseases. This article reviews the current indications
      and outcomes for the procedure and problems encountered in lung transplantation
      for interstitial lung diseases. The role of transplant for specific diseases also
      is discussed.

PMID- 15564023
TI  - An evaluation of mycophage therapy, chemotherapy and vaccination for control of
      Mycobacterium avium subsp. paratuberculosis infection.
AB  - The control of ovine Johne's disease (OJD) is important for domestic trade, the
      viability of farming units and possibly also for public health. Current
      strategies in Australia have included quarantine and pasture spelling to decrease
      prevalence and shedding rates and reduce numbers of Mycobacterium
      paratuberculosis (Mptb) ingested by susceptible sheep. However, alternative
      procedures are needed and vaccination with Gudair has recently commenced. This
      review examines prospects for the control of OJD by chemotherapy, vaccination and
      mycophages. Current chemotherapeutic regimes for treatment of M. paratuberculosis
      in ruminants are prohibitively expensive and of dubious efficacy, and apart from
      environmental concerns, mycophage therapy lacks a track record of success against
      intracellular bacteria. There is substantial evidence that live and killed
      mycobacterial vaccines reduce the incidence of clinical disease and shedding
      rates in OJD. An appraisal of recent experimental results suggests that neonatal
      vaccination with a defined dose of M. paratuberculosis offers the best prospects
      for the induction of protective Th1-type immunity.

PMID- 15564024
TI  - Colostral transmission of maedi visna virus: sites of viral entry in lambs born
      from experimentally infected ewes.
AB  - Maedi visna virus (MVV) vertical transmission in sheep via infected colostrums is
      a very important route of infection in lambs. To verify colostral transmission
      and to study early viral entry in lambs, colostrum samples, and small intestine
      and mesenteric lymph nodes of lambs born from experimentally infected ewes were
      examined by histopathology, immunohistochemistry (IHC) and in situ hybridisation
      (ISH) studies. In particular, newborn lambs were naturally fed maternal colostrum
      and humanely killed at 10, 24, 48, 72, 96 h and 7 and 10 days after birth; two
      caesarian-derived lambs served as uninfected controls. No lesions suggestive of
      MVV infection were found, but marked immunoreactions for MVV capsid antigen (CA,
      p28) were detected in lambs fed maternal colostrum and in macrophages cultured
      from colostrum. IHC results in lambs suggest an initial viral absorption by
      intestinal epithelial cells at the tip of the villi, passage to mononuclear cells
      in the lamina propria and involvement of ileum Peyers' patches and mesenteric
      lymph nodes, with different staining patterns depending on infection times. ISH
      on intestinal sections of the 72 h lamb revealed the presence of proviral DNA in
      epithelial cells at the tip of the villi, suggesting a role for these cells in
      early MVV replication. The results contribute to knowledge about the pathogenesis
      of ovine lentivirus infection suggesting that the small intestine and mesenteric
      nodes are the sites of entry and propagation of MVV in lambs fed colostrums from
      infected ewes.

PMID- 15564025
TI  - A long-term study in Merino sheep experimentally infected with Mycobacterium
      avium subsp. paratuberculosis: clinical disease, faecal culture and immunological
      studies.
AB  - Two longitudinal experiments involving Merino sheep challenged with either bovine
      or ovine strains of Mycobacterium avium subsp. paratuberculosis (Map) have been
      conducted over a period of 54 and 35 months, respectively. Blood samples for the
      interferon-gamma test, the absorbed ELISA and faecal samples for bacteriological
      culture were taken pre-challenge and monthly post-challenge. Infections were
      induced with either a bovine or ovine strain of Map in separate experiments with
      infections being more easily established, in terms of faecal bacterial shedding
      and clinical disease when the challenge inoculum was prepared from gut mucosal
      tissue than cultured bacteria. The patterns of response for shedding and clinical
      disease were similar. Cell-mediated immune responses were proportionally elevated
      by at least an order of magnitude in all sheep dosed with either a bovine or
      ovine strain of Map. Conversely, antibody responses were only elevated in a
      relatively small proportion of infected sheep. Neither of the clinically affected
      tissue challenged sheep developed an antibody response despite the presence of
      persistent shedding and the development and decline in cell-mediated immunity.
      The results indicated that for sheep the interferon-gamma test may be useful for
      determining if a flock has been exposed to ovine Johne's disease.

PMID- 15564026
TI  - Identification of a novel collagen-like protein, SclC, in Streptococcus equi
      using signal sequence phage display.
AB  - Strangles is a serious disease in horses caused by Streptococcus equi subspecies
      equi. In this study, genes encoding putative extracellular proteins in this
      subspecies have been identified using signal sequence phage display. Among these,
      one showed similarities to the SclB protein, a member of the collagen-like
      proteins of Streptococcus pyogenes. The novel gene denoted sclC encodes a
      protein, SclC, of 302 amino acids, containing typical features found in cell wall
      anchored proteins in Gram-positive bacteria. Based on similarities to the S.
      pyogenes collagen-like proteins the mature SclC protein can be divided into
      various domains: an N-terminal non-repetitive region (A), a highly repetitive
      collagen-like region (CL), and a C-terminal proline-rich wall-associated region
      (W). Using PCR, the sclC gene was detected in all studied strains of S. equi
      subsp. equi and S. equi subsp. zooepidemicus. Further, antibodies against
      recombinant SclC were detected in a collection of sera from horses with no
      history of strangles as well as horses previously infected with S. equi subsp.
      equi. Interestingly, the sera from convalescence horses were found to have
      significantly increased antibody titers against the SclC protein indicating that
      this protein is expressed during infection of S. equi subsp. equi.

PMID- 15564027
TI  - Antimicrobial resistance of Salmonella isolated from finishing swine and the
      environment of 60 Alberta swine farms.
AB  - The study objective was to describe and evaluate antimicrobial resistance
      profiles in Salmonella isolated from Alberta swine finishing farms. Salmonella
      isolates (n = 322) were obtained from 192 fecal and 84 environmental samples of
      the 60 Salmonella-positive swine finishing farms. Isolates were classified
      susceptible, intermediate or resistant based on NCCLS guidelines. More than half
      of the isolates (53.4%) were susceptible to all of the 18 antimicrobials in the
      testing panel. No resistance was observed to amikacin, amoxicillin/clavulanic
      acid, cefoxitin, ceftiofur, ceftriaxone, cephalothin, ciprofloxacin, imipenem or
      nalidixic acid. Less than 1% of isolates were resistant to apramycin, gentamicin
      and trimethoprim/sulfamethoxazole. Higher frequencies of resistance were observed
      for chloramphenicol (4.7%), ampicillin (7.8%), kanamycin (11.8%),
      sulfamethoxazole (21.1%), streptomycin (25.5%) and tetracycline (38.8%). Eleven
      Salmonella serovars had isolates with resistance to > or =3 antimicrobials. The
      most frequently resistant serovar was Salmonella Derby, with 27 (38.0%) isolates
      resistant to > or =3 antimicrobials, including resistance to five and six
      antimicrobials. An absence of resistance to cephalosporins and fluoroquniolones
      and a low proportion of isolates resistant to amikacin, amoxicillin/clavulanic
      acid, apramycin, gentamicin and trimethoprim/sulfamethoxazole are encouraging
      findings from public health and animal health perspectives. Frequent resistance
      observed for ampicillin, kanamycin, sulfamethoxazole, streptomycin and
      tetracycline, antimicrobials commonly used in veterinary medicine for decades,
      indicates an urgent need to utilize these antimicrobials more prudently if their
      benefits are to be preserved.

PMID- 15564028
TI  - Infection dynamics of Lawsonia intracellularis in pig herds.
AB  - Little information is known about the natural course and within-herd prevalence
      of porcine proliferative enteropathy caused by Lawsonia intracellularis. The
      objective of the study was to investigate the within-herd dynamics of naturally
      acquired L. intracellularis infection in pigs from weaning to slaughter. The
      study was designed as a longitudinal survey where 100 pigs from five herds were
      randomly selected at weaning (approximately 4 weeks of age). Every second week
      until slaughter (10-12 times, i.e. 20-24 weeks) the pigs were weighed and faecal
      as well as blood samples were collected. Faecal shedding of L. intracellularis
      was assessed by real time-PCR and sero-conversion by an indirect
      immunofluorescence antibody test (IFAT). Clinical disease was not reported but
      infection was present in all herds and the PCR assay indicated infection in 75%
      of pigs examined. Most L. intracellularis infected pigs were shedding at 10-12
      weeks of age (22-29 kg) and shed for 2-6 successive weeks. After 18 weeks of age
      all shedding had ceased and re-infection at PCR detectable level was not seen.
      Variable L. intracellularis associated impact on growth rate was observed.
      Immediately before bacterial shedding and during early infection the average
      growth rate declined whereas a compensatory impact was observed during later
      infection and after bacterial shedding had ceased. The performance of the IFAT
      resembled the bacteriological test almost perfectly. Sero-conversion was first
      detected at 12-14 weeks of age. Relative to the bacterial shedding, the onset of
      sero-conversion was a little delayed, in general, most pigs had sero-converted 2
      weeks after the first shedding. Once sero-converted, 92% of the pigs remained
      sero-positive over the entire survey period.

PMID- 15564029
TI  - Genetic typing of bovine viral diarrhoea virus isolates from India.
AB  - Thirteen BVDV isolates collected in four geographic regions of India between 2000
      and 2002 were typed in 5'-UTR. To confirm results of genetic typing, selected
      viruses were also analysed in the N(pro) region. Phylogenetic analysis revealed
      that all Indian BVDV isolates belong to BVDV-1b (Osloss-like group). Despite a
      long distance between the farms from which the viruses were isolated there was no
      correlation between the origin of viral isolates and their position in a
      phylogenetic tree. Higher genetic similarity of Indian BVDV isolates was observed
      most probably due to the uncontrolled movement of cattle as well as the
      uncontrolled use of semen from bulls for breeding of local and farm cattle in
      different states of India.

PMID- 15564030
TI  - The p40* adhesin pseudogene of Mycoplasma bovis.
AB  - An analogue of the adhesin gene p40 of Mycoplasma agalactiae was found in
      Mycoplasma bovis. Nucleotide sequence analysis of the p40* gene in M. bovis
      revealed the presence of a large deletion involving a frameshift that causes
      premature truncation of the translated protein, indicating that p40* exists as a
      pseudogene in M. bovis.

PMID- 15564031
TI  - The high prevalence of Helicobacter sp. in porcine pyloric mucosa and its
      histopathological and molecular characteristics.
AB  - This study examined the prevalence of Helicobacter infection in the pyloric
      mucosa of pigs and its histopathological and molecular characteristics. Forty
      porcine pyloric samples were examined for Helicobacter infection by silver
      staining and PCR assay. The PCR product (376 bp) was digested with NdeII to
      differentiate between Helicobacter heilmannii and Helicobacter pylori. Another
      PCR assay run to produce an 1157 bp fragment was performed using a primer set
      designed from the 16S rRNA gene of Candidatus H. suis, and its product was cloned
      and sequenced. Infection rates were 62.5% (25/40) and 95.0% (38/40) as determined
      by silver staining and the PCR assay, respectively. On histopathological
      examination, lymphoid follicle aggregation in the pyloric mucosa and granulocytic
      migration into the lumen of pyloric glands were observed in 24 (60.0%) and 33
      (82.5%) gastric samples, respectively. All PCR products, except that of H.
      pylori, were cut into two fragments of 147 and 229 bp by enzymatic digestion with
      NdeII. Sequencing of the 16S rRNA gene showed that the bacterium had 99.57% (1152
      bp/1157 bp) homology to the 16S rRNA gene of Candidatus H. suis.

PMID- 15564032
TI  - Magnetic resonance imaging of muscle in nemaline myopathy.
AB  - We report muscle MRI findings of 10 patients from 8 families with nemaline
      myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent
      pattern of selective muscle involvement corresponding to clinical severity. In
      mild cases, there was complete sparing of thigh muscles and selective involvement
      of tibialis anterior and soleus. In moderate cases, there was predominant
      involvement of rectus femoris, vastus lateralis and hamstring muscles and diffuse
      involvement of anterior compartment and soleus. Patients with nemaline myopathy
      secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed
      diffuse involvement of thigh and leg muscles with relative sparing of the
      gastrocnemii. Selective muscle involvement in both genetic categories was
      distinct from what has been reported in other congenital myopathies. We conclude
      that muscle MRI may be applied to distinguish nemaline myopathy from other
      conditions with similar clinical and histopathological features, to supplement
      clinical assessment in individual patients and to help direct genetic testing.

PMID- 15564033
TI  - Magnetic resonance imaging of muscle in congenital myopathies associated with
      RYR1 mutations.
AB  - Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated
      with a wide range of phenotypes, comprising central core disease and distinct
      subgroups of multi-minicore disease. We report muscle MRI findings of 11 patients
      from eight families with RYR1 mutations (n=9) or confirmed linkage to the RYR1
      locus (n=2). Patients had clinical features of a congenital myopathy with a wide
      variety of associated histopathological changes. Muscle MR images showed a
      consistent pattern characterized by (a) within the thigh: selective involvement
      of vasti, sartorius, adductor magnus and relative sparing of rectus, gracilis and
      adductor longus; (b) within the lower leg: selective involvement of soleus,
      gastrocnemii and peroneal group and relative sparing of the tibialis anterior.
      Our findings indicate that patients with RYR1-related congenital myopathies have
      a recognizable pattern of muscle involvement irrespective of the variability of
      associated histopathological findings. Muscle MRI may supplement clinical
      assessment and aid selection of genetic tests particularly in patients with non
      diagnostic or equivocal histopathological features.

PMID- 15564034
TI  - Albumin targeting of damaged muscle fibres in the mdx mouse can be monitored by
      MRI.
AB  - Increased sarcolemmal permeability has been implicated as a major pathological
      event in muscular dystrophies. In our study, we evaluated whether damaged muscle
      fibres can be specifically targeted using albumin as a carrier. We tagged human
      serum albumin (HSA) with Gadolinium (Gd) and systemically applied this compound
      (Gd-DTPA-HSA) to wildtype and dystrophin-deficient mdx mice. We performed
      magnetic resonance imaging before and after intravenous administration of Gd-DTPA
      HSA and found localised signal enhancement only in mdx skeletal muscle. We also
      examined skeletal muscle after contrast enhanced magnetic resonance imaging using
      anti-human albumin antibodies and demonstrated intracellular accumulation of Gd
      DTPA-HSA in clusters of damaged mdx muscle fibres. Comparison of magnetic
      resonance imaging and histological data emphasised the value of contrast agent
      enhanced magnetic resonance imaging for the in vivo assessment of fibre damage in
      muscular dystrophies. Furthermore, our data provide evidence that albumin can be
      used as a carrier to target covalently bound molecules to degenerating muscle
      fibres.

PMID- 15564035
TI  - Sleep disordered breathing in spinal muscular atrophy.
AB  - Sleep disordered breathing is a common but under-diagnosed complication causing
      sleep disturbance and daytime symptoms in children with spinal muscular atrophy.
      Non-invasive (positive pressure) ventilation is an established treatment of
      respiratory failure; its role in treatment of sleep disordered breathing though
      remains controversial. Aim of this study was to verify the hypothesis that
      nocturnal non-invasive ventilation has beneficial impact on breathing during
      sleep, sleep quality and daytime complaints in children with spinal muscular
      atrophy. Twelve children with spinal muscular atrophy type I or II (7.8+/-1.9
      years) underwent polysomnography and were asked to fill out a symptom
      questionnaire. Seven patients (six with spinal muscular atrophy I and one with
      spinal muscular atrophy II) had sleep disordered breathing and received non
      invasive ventilation during sleep. Five less severely affected patients (one with
      spinal muscular atrophy I and four with spinal muscular atrophy II) had no sleep
      disordered breathing and served as reference group. Patients were restudied after
      6-12 months. In patients with sleep disordered breathing both sleep architecture
      and disease related symptoms were significantly worse than in the reference
      group. Non-invasive ventilation during sleep completely eliminated disordered
      breathing, normalized sleep architecture and improved symptoms (P<0.05 for all).
      In children with spinal muscular atrophy sleep disordered breathing may cause
      relevant impairment of sleep and well-being. Both can be highly improved by
      nocturnal non-invasive ventilation.

PMID- 15564036
TI  - Application of multiplex ligation-dependent probe analysis to define a small
      deletion encompassing PMP22 exons 4 and 5 in hereditary neuropathy with liability
      to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies arises as a result of
      defects at the chromosome 17p11.2-12 locus and in 84% of cases a 1.5 Mb deletion
      containing the PMP22 gene is detected by analysis that utilises polymorphic (CA)n
      repeat markers which flank this gene. We report the clinical and
      electrophysiological findings observed in a kindred with three members affected
      by HNPP due to a deletion containing exons 4 and 5 of the PMP22 gene. This small
      deletion cannot be detected using standard analysis with polymorphic (CA)n repeat
      markers and a definitive diagnosis was made by multiplex ligation-dependent probe
      analysis of PMP22 exons 1A-5. MLPA can be readily utilised as a routine
      diagnostic laboratory test to detect the common HNPP 1.5 Mb deletion, as well as
      the reciprocal 1.5 Mb insertion observed in CMT1A, but has the advantage over
      other diagnostic techniques of being able to define single exon deletions.

PMID- 15564037
TI  - Two novel CAV3 gene mutations in Japanese families.
AB  - Caveolin-3 deficiency is a rare, autosomal dominant, muscle disorder caused by
      caveolin-3 gene (CAV3) mutations and consists of four clinical phenotypes: limb
      girdle muscular dystrophy type 1C (LGMD-1C), rippling muscle disease, distal
      myopathy, and familial hyperCKemia. So far, only 13 mutations have been reported.
      We here report two novel heterozygous mutations, 96C>G (N32K) and 128T>A (V43E),
      in the CAV3 gene in two unrelated Japanese families with LGMD-1C. Both probands
      presented with elevated serum CK level with calf muscle hypertrophy in their
      childhood but without apparent muscle weakness. However, their mothers showed
      mild limb-girdle weakness in addition to high CK level. Caveolin-3 was deficient
      and caveolae were lacking in muscles from both patients. Our data confirm that
      caveolin-3 deficiency causes LGMD-1C and expand the variability in CAV3 gene
      mutations.

PMID- 15564038
TI  - Mitochondrial myopathy and ophthalmoplegia in a sporadic patient with the 5698G-
      >A mitochondrial DNA mutation.
AB  - We describe a second patient carrying the 5698G-->A transition in the
      mitochondrial DNA gene encoding tRNA(Asn), who has an apparently isolated
      mitochondrial myopathy with chronic progressive external ophthalmoplegia. A
      muscle biopsy showed the presence of ragged-red and COX-negative fibres. Analysis
      of the mutation load on single muscle fibres showed significant segregation of
      the 5698G-->A with COX-depleted fibres. These results indicate that the 5698G-->A
      is pathogenic.

PMID- 15564039
TI  - A case of severe congenital chronic inflammatory demyelinating polyneuropathy
      with complete spontaneous remission.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIPD) is characterised by
      progressive weakness, hyporeflexia and electrophysiological evidence of
      demyelination with maximal neurological deficit reached after at least 8 weeks
      progression. CIPD rarely affects children. We present a neonate with clinical
      features compatible with congenital CIPD. A term male infant of non
      consanguineous parents was referred to us at birth with weakness and contractures
      affecting his legs, suggesting a prenatal onset of immobility. He also had
      evidence of bulbar dysfunction with poor suck, recurrent aspiration and requiring
      nasogastric feeding. He had no antigravity movements in the legs, bilateral wrist
      drop, distal joint contractures and absent deep tendon reflexes. Electromyography
      showed neurogenic changes, with nerve conduction velocities markedly reduced,
      increased distal motor latency and dispersed compound muscle action potentials.
      Cerebrospinal fluid protein was raised. Sural nerve biopsy demonstrated decreased
      numbers of myelinated fibres and inflammatory cell infiltrates. Muscle biopsy
      showed denervation. He only received supportive treatment and by 6 months he had
      fully recovered, and all electrophysiological parameters had normalised.

PMID- 15564040
TI  - The Eighth Meryon Society Lecture read at Worcester College, Oxford on 2 July,
      2004.

PMID- 15564041
TI  - TGF-beta activation by traction?
AB  - Transforming growth factor (TGF)-betas are powerful cytokines that are secreted
      as inactive (latent) precursors into the extracellular space. To exert their
      pleiotropic functions, latent TGF-betas require activation. This requisite
      restricts TGF-beta signaling to tissues that express TGF-beta-activating proteins
      such as the adhesion molecule alphavbeta6 integrin. Recent work has uncovered the
      molecular mechanism by which alphavbeta6 integrin activates latent TGF-beta.
      Latent-TGF-beta-binding protein 1 has been identified as being the major
      component of this process, and the integrin-interacting region has been mapped to
      a poorly conserved sequence stretch called the hinge region.

PMID- 15564042
TI  - Computational approaches for modeling regulatory cellular networks.
AB  - Cellular components interact with each other to form networks that process
      information and evoke biological responses. A deep understanding of the behavior
      of these networks requires the development and analysis of mathematical models.
      In this article, different types of mathematical representations for modeling
      signaling networks are described, and the advantages and disadvantages of each
      type are discussed. Two experimentally well-studied signaling networks are then
      used as examples to illustrate the insight that could be gained through modeling.
      Finally, the modeling approach is expanded to describe how signaling networks
      might regulate cellular machines and evoke phenotypic behaviors.

PMID- 15564043
TI  - Flippases and vesicle-mediated protein transport.
AB  - The best-understood mechanisms for generating transport vesicles in the secretory
      and endocytic pathways involve the localized assembly of cytosolic coat proteins
      such as clathrin, coat protein complex (COP)I and COPII onto membranes. These
      coat proteins can deform membranes by themselves, but accessory proteins might
      help to generate the tight curvature needed to form a vesicle. Enzymes that pump
      phospholipid from one leaflet of the bilayer to the other (flippases) can deform
      membranes by creating an imbalance in the phospholipid number between the two
      leaflets. Recent studies describe a requirement for the yeast Drs2p family of P
      type ATPases in both phospholipid translocation and protein transport in the
      secretory and endocytic pathways. This indicates that flippases work with coat
      proteins to form vesicles.

PMID- 15564044
TI  - Integrins: versatile integrators of extracellular signals.
AB  - Extracellular matrix (ECM) molecules and growth factors have a crucial role in
      the signalling that controls cell behaviour during development. Integrins, which
      are cell-surface receptors for ECM molecules, and growth factor receptors
      cooperate with each other to regulate this signalling by several mechanisms. In
      particular, direct interactions between the integrin and growth factor receptors
      themselves, which often occur within a single macromolecular complex, amplify
      signalling by mechanisms that include posttranslational modifications and
      integrin shape changes that are related to activation. As a result, growth factor
      concentrations in the physiological range, which are too low to initiate
      signalling alone, do so in the presence of the ECM, enabling integrins to control
      the time and space of growth factor signalling.

PMID- 15564045
TI  - Arf-like GTPases: not so Arf-like after all.
AB  - ADP-ribosylation factor (Arf) GTP-binding proteins are among the best
      characterized members of the Ras superfamily of GTPases, with well-established
      functions in membrane-trafficking pathways. A recent watershed of genomic and
      structural information has identified a family of conserved related proteins: the
      Arf-like (Arl) GTPases. The best-characterized Arl protein, Arl2, regulates the
      folding of beta tubulin, and recent data suggest that Arl1 and Arf-related
      protein 1 (ARFRP1) are localized to the trans-Golgi network (TGN), where they
      function, in part, to regulate the tethering of endosome-derived transport
      vesicles. Other Arl proteins are localized to the cytosol, nucleus, cytoskeleton
      and mitochondria, which indicates that Arl proteins have diverse roles that are
      distinct from the known functions of traditional Arf GTPases.

PMID- 15564046
TI  - Chromatin modifiers and carcinogenesis.
AB  - Access of gene regulatory factors to the eukaryotic genome is modulated by
      chromatin. The organization of this nucleoprotein complex is highly dynamic and
      tightly regulated. The control of wide-ranging nuclear processes through the
      configuration of chromatin is achieved by the concerted actions of ATP-dependent
      chromatin-remodeling complexes and histone-modifying enzymes, and by the
      incorporation of specialized histone variants. It is becoming clear that
      perturbation of these chromatin modifiers can lead to cancer. Recent findings
      illustrate the mechanisms by which chromatin influences cancer development, and
      aid understanding of the regulation of chromatin organization, cellular
      transformation and the connections between tumor suppressor and oncogene
      function.

PMID- 15564047
TI  - The ubiquitin-proteasome pathway in Parkinson's disease and other
      neurodegenerative diseases.
AB  - During the past decade, it has become apparent that a set of ostensibly unrelated
      neurodegenerative diseases, including Parkinson's disease and Huntington's
      disease, shares striking molecular and cell biology commonalities. Each of the
      diseases involves protein misfolding and aggregation, resulting in inclusion
      bodies and other aggregates within cells. These aggregates often contain
      ubiquitin, which is the signal for proteolysis by the 26S proteasome, and
      chaperone proteins that are involved in the refolding of misfolded proteins. The
      link between the ubiquitin-proteasome system and neurodegeneration has been
      strengthened by the identification of disease-causing mutations in genes coding
      for several ubiquitin-proteasome pathway proteins in Parkinson's disease.
      However, the exact molecular connections between these systems and pathogenesis
      remain uncertain and controversial. In this article, we summarize the state of
      current knowledge, focusing on important unresolved questions.

PMID- 15564049
TI  - Emerging interventions.

PMID- 15564050
TI  - Emerging brain-based interventions for children and adolescents: overview and
      clinical perspective.
AB  - Electroencephalogram biofeedback (EBF), repetitive transcranial magnetic
      stimulation (rTMS), and vagal nerve stimulation (VNS) are emerging interventions
      that attempt to directly impact brain function through neurostimulation and
      neurofeedback mechanisms. This article provides a brief overview of each of these
      techniques, summarizes the relevant research findings, and examines the
      implications of this research for practice standards based on the guidelines for
      recommending evidence based treatments as developed by the American Academy of
      Child and Adolescent Psychiatry for attention deficit hyperactivity disorder
      (ADHD). EBF meets the "Clinical Guidelines" standard for ADHD, seizure disorders,
      anxiety, depression, and traumatic brain injury. VNS meets this same standard for
      treatment of refractory epilepsy and meets the lower "Options" standard for
      several other disorders. rTMS meets the standard for "Clinical Guidelines" for
      bipolar disorder, unipolar disorder, and schizophrenia. Several conditions are
      discussed regarding the use of evidence based thinking related to these emerging
      interventions and future directions.

PMID- 15564051
TI  - The role of quantitative electroencephalography in child and adolescent
      psychiatric disorders.
AB  - This article presents a critical review of quantitative electroencephalographic
      (qEEG) research and issues relevant to its clinical application. Included is a
      summary of methodologic issues necessary for a reliable implementation of qEEG
      within clinical settings and a brief discussion of controversial issues
      surrounding this implementation. The main body of the article includes a summary
      of qEEG findings that involves adults with various neurologic and psychiatric
      disorders, which is followed by an in-depth presentation of qEEG research that
      involves children and adolescents with neurologic and psychiatric disorders. A
      concluding section presents a qEEG-based neurophysiologic model of attention
      deficit disorder.

PMID- 15564052
TI  - Electroencephalographic biofeedback (neurotherapy) as a treatment for attention
      deficit hyperactivity disorder: rationale and empirical foundation.
AB  - During the past three decades, electroencephalographic (EEG) biofeedback has
      emerged as a nonpharmacologic treatment for attention-deficit/hyperactivity
      disorder (ADHD). This intervention was derived from operant conditioning studies
      that demonstrated capacity for neurophysiologic training in humans and other
      mammals and targets atypical patterns of cortical activation that have been
      identified consistently in neuroimaging and quantitative EEG studies of patients
      diagnosed with ADHD. This article presents the rationale for EEG biofeedback and
      examines the empirical support for this treatment using efficacy guidelines
      established by the Association for Applied Psychophysiology and Biofeedback and
      the International Society for Neuronal Regulation. Based on these guidelines, EEG
      biofeedback is considered to be "probably efficacious" for the treatment of ADHD
      and merits consideration as a treatment for patients who are stimulant
      "nonresponders." Although research findings published to date indicate positive
      clinical response in approximately 75% of patients treated in controlled group
      studies, additional randomized, controlled trials are needed to provide a better
      estimate of the robustness of this treatment.

PMID- 15564053
TI  - Critical validation studies of neurofeedback.
AB  - The field of neurofeedback training has proceeded largely without validation. In
      this article the authors review studies directed at validating sensory motor
      rhythm, beta and alpha-theta protocols for improving attention, memory, and music
      performance in healthy participants. Importantly, benefits were demonstrable with
      cognitive and neurophysiologic measures that were predicted on the basis of
      regression models of learning to enhance sensory motor rhythm and beta activity.
      The first evidence of operant control over the alpha-theta ratio is provided,
      together with remarkable improvements in artistic aspects of music performance
      equivalent to two class grades in conservatory students. These are initial steps
      in providing a much needed scientific basis to neurofeedback.

PMID- 15564054
TI  - Neurofeedback with anxiety and affective disorders.
AB  - A robust body of neurophysiologic research is reviewed on functional brain
      abnormalities associated with depression, anxiety, and obsessive-compulsive
      disorder. A review of more recent research finds that pharmacologic treatment may
      not be as effective as previously believed. A more recent neuroscience
      technology, electroencephalographic (EEG) biofeedback (neurofeedback), seems to
      hold promise as a methodology for retraining abnormal brain wave patterns. It has
      been associated with minimal side effects and is less invasive than other methods
      for addressing biologic brain disorders. Literature is reviewed on the use of
      neurofeedback with anxiety disorders, including posttraumatic stress disorder and
      obsessive-compulsive disorder, and with depression. Case examples are provided.

PMID- 15564055
TI  - Applicability of brain wave biofeedback to substance use disorder in adolescents.
AB  - Neurofeedback treatment for addictions in adults is probably efficacious, and
      several reported approaches are described with their indications. Neurofeedback
      is promising as a treatment modality for adolescents, especially those with
      stimulant abuse and attention and conduct problems. It is attractive as a
      medication-free, neurophysiologic, and self-actualizing treatment for a substance
      based, brain-impaired and self-defeating disorder. More research, beginning with
      case reporting, is needed to assess use and efficacy in adolescents.

PMID- 15564056
TI  - Electroencephalogram biofeedback for reading disability and traumatic brain
      injury.
AB  - The application of electroencephalogram (EEG) biofeedback with reading disability
      and traumatic brain injury (TBI) is relatively recent. There are many studies
      regarding the effectiveness (improving attention and IQ scores) of EEG
      biofeedback in patients with attention deficit hyperactivity disorder, who are
      known to have a high rate of comorbidity for learning disabilities. This suggests
      the possibility that EEG biofeedback specifically aimed at remediating reading
      disability and TBI would be effective. This article provides strong initial
      support for this idea and provides reason to believe that assessment and training
      under task conditions are likely to be fruitful. Given the significance of these
      problems and the absence of very effective alternatives for remediation of these
      conditions, efforts to complete the needed research seem warranted. Clinical use
      of this intervention seems to be warranted with informed consent.

PMID- 15564057
TI  - Neurofeedback treatment of epilepsy.
AB  - With electroencephalographic (EEG) biofeedback (or neurofeedback), it is possible
      to train the brain to de-emphasize rhythms that lead to generation and
      propagation of seizure and emphasize rhythms that make seizures less likely to
      occur. With recent improvements in quantitative EEG measurement and improved
      neurofeedback protocols, it has become possible in clinical practice to eliminate
      seizures or reduce the amount of medication required to control them. In this
      article, the history of neurofeedback for epilepsy is presented followed by
      discussions of the relevant neurophysiology of epilepsy. A model of how
      neurofeedback might raise the seizure threshold is then presented. Clinical
      experience using a quantitative EEG-guided approach is described, including a
      representative case study.

PMID- 15564058
TI  - Vagus nerve stimulation: current use and potential applications in child and
      adolescent psychiatry.
AB  - Chronic and recurrent major depressive episodes are associated with significant
      morbidity and mortality, and available treatments often are ineffective or only
      partially effective. This issue is of particular concern in children and
      adolescents, because major affective disorders often begin early in life and
      follow a chronic, progressive course. Because the current treatment armamentarium
      for depressive episodes in this age group is limited, the investigation for safe
      and effective treatment interventions is warranted. Vagus nerve stimulation
      therapy has proven safety, tolerability, and efficacy in the treatment of
      epilepsy, and early findings suggest safety and efficacy in the treatments of
      adults with chronic and recurrent treatment-resistant mood disorders. This
      intervention also holds promise as a potential treatment in children and
      adolescents, although research is currently lacking.

PMID- 15564059
TI  - Electroconvulsive therapy and repetitive transcranial magnetic stimulation in
      children and adolescents: a review and report of two cases of epilepsia partialis
      continua.
AB  - Brain stimulation for the treatment of psychiatric disorders has received
      increasing attention over the past decade. The introduction of experimental means
      to stimulate the brain noninvasively with magnetic fields not only has raised
      interest in these novel means of modulating brain activity but also has refocused
      attention on a mainstay in the treatment of severe major depression and other
      disorders (electroconvulsive therapy). This article reviews the current state of
      knowledge concerning the use electroconvulsive therapy, repetitive transcranial
      magnetic stimulation, and magnetic seizure therapy in children and adolescents.
      Two cases of medically intractable epilepsia partialis continua are presented to
      add to the limited literature on the use of repetitive transcranial magnetic
      stimulation in children and adolescents and illustrate the concept of using
      functional neuroimaging results to target the application of a focal intervention
      in an attempt to dampen hyperactive regions of the cortex.

PMID- 15564060
TI  - Chondrocyte mechanotransduction: effects of compression on deformation of
      intracellular organelles and relevance to cellular biosynthesis.
AB  - OBJECTIVE: The effects of mechanical deformation of intact cartilage tissue on
      chondrocyte biosynthesis in situ have been well documented, but the
      mechanotransduction pathways that regulate such phenomena have not been
      elucidated completely. The goal of this study was to examine the effects of
      tissue deformation on the morphology of a range of intracellular organelles which
      play a major role in cell biosynthesis and metabolism. DESIGN: Using chemical
      fixation, high pressure freezing, and electron microscopy, we imaged chondrocytes
      within mechanically compressed cartilage explants at high magnification and
      quantitatively and qualitatively assessed changes in organelle volume and shape
      caused by graded levels of loading. RESULTS: Compression of the tissue caused a
      concomitant reduction in the volume of the extracellular matrix (ECM),
      chondrocyte, nucleus, rough endoplasmic reticulum, and mitochondria.
      Interestingly, however, the Golgi apparatus was able to resist loss of
      intraorganelle water and retain a portion of its volume relative to the remainder
      of the cell. These combined results suggest that a balance between intracellular
      mechanical and osmotic gradients govern the changes in shape and volume of the
      organelles as the tissue is compressed. CONCLUSIONS: Our results lead to the
      interpretive hypothesis that organelle volume changes appear to be driven mainly
      by osmotic interactions while shape changes are mediated by structural factors,
      such as cytoskeletal interactions that may be linked to extracellular matrix
      deformations. The observed volume and shape changes of the chondrocyte organelles
      and the differential behavior between organelles during tissue compression
      provide evidence for an important mechanotransduction pathway linking
      translational and post-translational events (e.g., elongation and sulfation of
      glycosaminoglycans (GAGs) in the Golgi) to cell deformation.

PMID- 15564061
TI  - Removal of the superficial zone of bovine articular cartilage does not increase
      its frictional coefficient.
AB  - OBJECTIVE: To investigate the role of the superficial zone in regulating the
      frictional response of articular cartilage. This zone contains the superficial
      protein (SZP), a proteoglycan synthesized exclusively by superficial zone
      chondrocytes and implicated in reducing the friction coefficient of cartilage.
      DESIGN: Unconfined compression creep tests with sliding of cartilage against
      glass in saline were carried out on fresh bovine cylindrical plugs (slashed
      circle O6 mm, n=35) obtained from 16 bovine shoulder joints (ages 1-3 months). In
      the first two experiments, friction tests were carried out before and after
      removal of the superficial zone ( approximately 100 microm), in a control and
      treatment group, using two different applied load magnitudes (4.4 N and 22.2 N).
      In the third experiment, friction tests were conducted on intact surfaces and the
      corresponding microtomed deep zone of the same specimen. RESULTS: In all tests
      the friction coefficient exhibited a transient response, increasing from a
      minimum value (mu(min)) to a near-equilibrium final value (micro(eq)). No
      statistical change (P>0.5) was found in micro(min) before and after removal of
      the superficial zone in both experiments 1 and 2. However, micro(eq) was observed
      to decrease significantly (P<0.001) after removal of the surface zone. Results
      from the third experiment confirm that micro(eq) is even lower at the deep zone.
      Surface roughness measurements with atomic force microscopy (AFM) revealed an
      increase in surface roughness after microtoming. Immunohistochemical staining
      confirmed the presence of SZP in intact specimens and its removal in microtomed
      specimens. CONCLUSIONS: The topmost ( approximately 100 microm) superficial zone
      of articular cartilage does not have special properties which enhances its
      frictional response.

PMID- 15564062
TI  - The effects of cyclic mechanical strain and tumor necrosis factor alpha on the
      response of cells of the meniscus.
AB  - OBJECTIVES: Cells of the knee meniscus respond to changes in their biochemical
      and biomechanical environments with alterations in the biosynthesis of matrix
      constituents and inflammatory mediators. Tumor necrosis factor alpha (TNF-alpha)
      is a pro-inflammatory cytokine that is involved in the pathogenesis of both
      osteoarthritis and rheumatoid arthritis, but its influence on meniscal physiology
      or mechanobiology is not fully understood. The objectives of this study were to
      examine the hypothesis that cyclic mechanical strain of meniscal cells modulates
      the biosynthesis of matrix macromolecules and pro-inflammatory mediators, and to
      determine if this response is altered by TNF-alpha. METHODS: Cells were isolated
      from the inner two-thirds of porcine medial menisci and subjected to biaxial
      tensile strain of 5-15% at a frequency of 0.5Hz. The synthesis of proteoglycan,
      protein, nitric oxide (NO), and prostaglandin E(2) were determined. RESULTS:
      Cyclic tensile strain increased the production of nitric oxide through the
      upregulation of nitric oxide synthase 2 (NOS2) and also increased synthesis rates
      of prostaglandin E(2), proteoglycan, and total protein in a manner that depended
      on strain magnitude. TNF-alpha increased the production of NO and total protein,
      but inhibited proteoglycan synthesis rates. TNF-alpha prevented the mechanical
      stimulation of proteoglycan synthesis, and this effect was not dependent on NOS2.
      CONCLUSIONS: These findings indicate that pro-inflammatory cytokines can modulate
      the responses of meniscal cells to mechanical signals, suggesting that both
      biomechanical and inflammatory factors could contribute to the progression of
      joint disease as a consequence of altered loading of the meniscus.

PMID- 15564063
TI  - Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage.
AB  - OBJECTIVE: To understand the molecular mechanisms that lead to increased MMP-13
      expression and cartilage degeneration during the progression of osteoarthritis
      (OA), we have investigated the expression of the transcription factor RUNX2 in OA
      cartilage and the regulation of MMP-13 expression by RUNX2 and FGF2 in articular
      chondrocytes. DESIGN: RUNX2 and MMP-13 expression in human OA and control
      cartilage was analyzed by immunohistochemistry. The effects of RUNX2 over
      expression, with or without FGF2 treatment, on MMP-13 promoter activity and
      enzyme accumulation were measured in articular chondrocytes. Inhibitors of
      MEK/ERK were assayed for their ability to block FGF2 and RUNX2 up-regulation of
      the MMP-13 promoter. We analyzed RUNX2 phosphorylation in response to FGF2.
      RESULTS: Fibrillated OA cartilage exhibited increased RUNX2 immunoreactivity when
      compared to control cartilage. RUNX2 co-localized with MMP-13 in clusters of
      chondrocytes in fibrillated OA cartilage. RUNX2 over-expression in cultured
      chondrocytes increased their responsiveness to FGF2 treatment, which led to
      increased MMP-13 expression. Inhibitors of MEK/ERK signaling blocked up
      regulation of the MMP-13 promoter by RUNX2 and FGF2, and also blocked the
      activation of RUNX2 by FGF2. FGF2 treatment of articular chondrocytes increased
      RUNX2 phosphorylation approximately 2-fold. CONCLUSIONS: Increased expression of
      RUNX2 in OA cartilage may contribute to increased expression of MMP-13. FGF2,
      which is present in OA synovial fluid, activated RUNX2 via the MEK/ERK pathway
      and increased MMP-13 expression. However, it is unlikely that RUNX2 is a
      substrate of ERK1/2. RUNX2 expression and activation may be a significant step in
      the progression of OA by promoting changes in gene expression and chondrocyte
      differentiation.

PMID- 15564064
TI  - The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis
      and cartilage degeneration following ovine meniscectomy.
AB  - AIM: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO)
      donor compound, on the concurrent progression of cartilage and subchondral bone
      changes in an ovine meniscectomy model of osteoarthritis (OA). METHODS: Bilateral
      lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated
      with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non
      operated controls (NOC). After sacrifice at six months, the subchondral bone
      density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial
      plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was
      performed across the MTP and LTP. Histological sections from each region were
      scored qualitatively and the thickness of the subchondral bone plate (SCB) was
      determined by image analysis. RESULTS: MX+GTN displayed significantly greater SCB
      thickness relative to MX in the LFC (mean increase +88% and +42%, respectively)
      and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP
      and MTP. MX+GTN sheep also showed greater increases in some histopathology
      variables, greater central erosion of the LTP, and changes in dynamic stiffness
      (decreased) and phase lag (increased) in the outer zone of the LTP. CONCLUSIONS:
      Treatment with GTN significantly increased subchondral bone thickness and density
      during subchondral remodelling following meniscectomy. In addition, it slightly
      but significantly worsened degeneration of cartilage structure and function.
      These results suggest that clinical use of GTN may accelerate both cartilage
      degeneration and subchondral bone sclerosis if used in the presence of OA, and
      demonstrate that NO has the potential be an important mediator of the subchondral
      bone changes seen in OA.

PMID- 15564065
TI  - Chromosomal abnormalities are related to location and grade of osteoarthritis.
AB  - OBJECTIVE: To investigate the frequency of numerical aberrations of chromosomes
      7, X and Y in patients with osteoarthritis (OA) by performing fluorescent in situ
      hybridization (FISH) studies on articular cartilage, and to correlate the
      chromosomal changes with the degree and location of articular involvement.
      PATIENTS: Thirty-four women and 10 men with OA were included in the study. As a
      control group, 6 women and 5 men operated for orthopedic disorders other than OA
      were analyzed. METHODS: FISH studies were performed on hip or knee cartilage,
      using two-color centromere-specific probes for chromosomes 7 & X for women and 7
      & Y for men. RESULTS: FISH analysis revealed that 46% of OA patients had
      numerical abnormalities of chromosomes 7, X or Y. An extra chromosome 7 (trisomy
      7) was present in 35% of patients with chromosomal aberrations. All males with OA
      lost the Y chromosome while 15% of the women had loss of one chromosome X
      (monosomy X). Trisomy 7 was associated with hip OA (p=0.019) and advanced OA
      according to the Kellgren and Lawrence classification (p=0.05). None of the 11
      controls showed abnormalities in the chromosomes analyzed. CONCLUSIONS: FISH
      analysis showed the presence of numerical chromosomal abnormalities in the
      articular cartilage of patients with OA.

PMID- 15564066
TI  - Ex vivo characterization of articular cartilage and bone lesions in a rabbit ACL
      transection model of osteoarthritis using MRI and micro-CT.
AB  - OBJECTIVE: To characterize the rabbit anterior cruciate ligament transection
      (ACLT) model of osteoarthritis (OA) at various stages of disease using high
      resolution 3-D medical imaging systems, which, in turn, will facilitate future
      longitudinal studies evaluating disease progression and response to therapy in
      live animals. METHODS: Degenerative changes in femorotibial cartilage, volumetric
      bone mineral density (vBMD), bone volume fraction (BV/TV), and osteophyte volume
      were characterized ex vivo using 4-T magnetic resonance imaging (MRI) and micro
      computed tomography (micro-CT) at 4, 8, and 12 weeks post-ACLT. These changes
      were subsequently correlated to macroscopic joint evaluation. RESULTS:
      Macroscopic assessment demonstrated progressive cartilage degeneration post
      surgery, which was significantly correlated to MRI evaluation (r=0.82, P<0.0001).
      Linear regression analysis indicated that vBMD and BV/TV are linearly related
      such that as vBMD increases, BV/TV increases (P<0.0001). Micro-CT revealed bone
      loss at 4 and 8 weeks post-ACLT, but recovery to control values at 12 weeks post
      ACLT. Volumetric BMD was not strongly correlated with macroscopic assessment of
      articular cartilage degeneration (r=-0.35, P<0.0001). Quantitative measurement of
      osteophyte volume demonstrated a statistically significant difference (with
      respect to control groups) at both 8 and 12 weeks post-ACLT, but not at 4 weeks
      post-ACLT. CONCLUSIONS: The rabbit ACLT model of OA demonstrates progressive
      cartilage degeneration and intermediate bone changes at 4, 8, and 12 weeks post
      surgery. Cartilage and bone lesions were characterized ex vivo using 4-T MRI and
      micro-CT, and MRI assessment of cartilage degeneration was correlated to
      macroscopic grading.

PMID- 15564067
TI  - A pilot, two-year longitudinal study of the interrelationship between trabecular
      bone and articular cartilage in the osteoarthritic knee.
AB  - OBJECTIVE: To examine the relationship between structural changes of trabecular
      bone and cartilage, in patients with varying degrees of osteoarthritis (OA) over
      2 years, using magnetic resonance imaging. METHODS: High-resolution, axial images
      were acquired for assessing trabecular bone structure, using a 3-D fast gradient
      echo sequence. High-resolution, fat-suppressed, sagittal images were acquired for
      assessing cartilage structure, using a 3-D spoiled gradient-echo sequence. In a
      subset of the patients, sagittal images were acquired for measuring T(2)
      relaxation time, using a 2-D dual-echo spin echo sequence. RESULTS: A large
      variation in bone and cartilage parameters is evident among individual subjects
      in each group, however, group-specific means demonstrate decreasing trends (in
      bone and cartilage parameters) in osteoarthritic subjects (especially in mild OA
      subjects). The mean T(2) increased significantly (P<0.05) between the baseline
      and follow-up exams for all cartilage compartments except the lateral tibia. A
      positive relationship was established between cartilage changes and localized
      bone changes closest to the joint line, while a negative relationship was
      established between cartilage changes and global bone changes farthest from the
      joint line. CONCLUSION: This study quantifies the changes in bone and cartilage
      structural parameters over time, and demonstrates a longitudinal relationship
      between the morphological changes in bone and cartilage structure in patients
      with varying degrees of OA. Although a large variation of bone and cartilage
      changes is apparent among subjects, significant trends are evident in a
      relatively small sample size, with a short follow-up duration.

PMID- 15564068
TI  - Cartilage degradation independent of MMP/aggrecanases.
AB  - OBJECTIVE: To identify and characterize a cartilage degradation mechanism that is
      independent of the proteolytic cleavages by matrix metalloproteinases (MMPs) and
      aggrecanases. METHODS: The sensitivity of glycosaminoglycan (GAG) release and
      collagen release to an MMP/aggrecanase inhibitor, AG3340, was compared using a
      bovine nasal cartilage explant culture. The release of matrix proteins and
      hyaluronan (HA) from the culture was analyzed by immunoblotting and
      radioimmunoassay, respectively. Induction of HA-degrading activity by retinoic
      acid was examined using the cartilage explant culture and a primary culture of
      chondrocytes. Degradation of the matrix components of cartilage was also
      characterized in vivo using an acute arthritis model induced by an intra
      articular injection of interleukin 1alpha (IL-1alpha). RESULTS: AG3340 did not
      effectively inhibit GAG release at a concentration of more than 10muM, while 10nM
      of the inhibitor completely suppressed collagen degradation. Retinoic acid
      induced the release of the aggrecan G1 domain, link protein and HA into the
      culture medium, and the release of these molecules was not completely inhibited
      by 10muM of AG3340. The molecules were released as ternary complexes. Retinoic
      acid induced HA degradation in the explant culture and hyaluronidase activity in
      the primary culture of chondrocytes. The release of the G1 domain of aggrecan and
      link protein into the synovial fluid was also observed in the IL-1alpha-induced
      acute arthritis model. CONCLUSION: A novel mechanism by chondrocyte-derived
      hyaluronidase(s) is involved in the release of the matrix components from
      cartilage, and the hyaluronidase(s) and MMPs/aggrecanases act in a coordinated
      manner in cartilage degradation.

PMID- 15564070
TI  - Cough as a symptom.
AB  - The Third International Symposium on Cough focused on acute and chronic cough,
      both clinical and basic science. Cough is a defensive and clearing mechanism, and
      can cause discomfort and nuisance; it is also an important symptom of many
      chronic airway diseases. In this Symposium, several issues concerning the
      relationship of cough to disease processes, different types of cough, and the
      concept of idiopathic cough will be discussed. Characterization of cough
      receptor(s) and identification of peripheral and central mechanisms for cough
      sensitization are current areas of investigation for delineating the cause of
      chronic cough. Peripheral mechanisms may be most important for acute cough such
      as after viral infections. The role of pathological changes at the level of the
      airway mucosa and of cortical pathways will be reviewed. Finally, therapeutic
      inhibition of the cough reflex remains an area of active research.

PMID- 15564071
TI  - Pathophysiology of airway viral infections.
AB  - Viral infections are major causes of cough. Virus-induced changes in airway
      sensory nerve function include increased tachykinin expression and, more
      specifically, expression of tachykinins by Adelta fibers. This change may be
      mediated by neurotrophins produced in response to viral infection. At the same
      time, activity of neutral endopeptidase, an enzyme that is important in degrading
      and inactivating tachykinins, is decreased by airway viral infections. Viral
      infections can activate eosinophils, releasing proteins that can cause tachykinin
      release. Moreover, expression of the NK1 receptor is increased by viral
      infections of the lungs. The expression of M2 muscarinic receptors, which
      normally decrease the sensitivity of sensory nerves, is decreased by viral
      infections. So it is possible that viral infections (1) increase expression of
      tachykinins (by causing neurotrophin expression), (2) increase release of
      tachykinins (by causing release of eosinophil proteins), (3) decrease degradation
      of tachykinins (by decreasing neutral endopeptidase activity), (4) increase
      expression of the NK1 receptor (again mediated by neurotrophins), and (5)
      increase the sensitivity of airway afferents (by decreasing M2 muscarinic
      receptor expression). All these changes may potentiate the tachykininergic input
      into the cough reflex, and may provide new therapeutic targets for controlling
      virus-induced cough.

PMID- 15564072
TI  - Cough induced by airway vibration as a model of airway hyperreactivity in
      patients with acute upper respiratory tract infection.
AB  - Patients with acute upper respiratory tract infection (URTI) have been shown to
      be hyperreactive to inhaled tussigens such as citric acid and capsaicin, and the
      authors propose that this may be due to an increased sensitivity of airway
      receptors that mediate cough. In recent studies we have demonstrated that cough
      may be induced by vibration of the airway at the level of the throat or chest in
      patients with URTI but that the same stimuli induce little or no cough in healthy
      subjects. The difference between the patients with URTI and healthy subjects in
      their response to airway vibration may be explained on the basis of
      hyperreactivity of airway sensory receptors. We propose that the model of cough
      induced by airway vibration may be useful for studies on the pathophysiology and
      pharmacology of airway hyperreactivity in acute cough. The airway vibration model
      of cough may have some advantages over inhaled tussigens as the stimulus is
      easily controlled and the method is safe for use in children.

PMID- 15564073
TI  - Post-nasal drip syndrome--a symptom to be sniffed at?
AB  - The syndrome or pseudo-syndrome of post-nasal drip (PNDS) represents a diagnostic
      label which is unhelpful in the understanding of chronic cough. There is no
      accepted definition of PNDS and no accepted method of measurement. The symptom of
      mucus dripping down the back of the throat occurs in normal subjects and is also
      reported by many patients in ENT clinics who do not have a cough. The lack of any
      clear pathological or biochemical tests makes the syndrome both a catch-all and a
      dustbin.

PMID- 15564074
TI  - Idiopathic pulmonary fibrosis: a nervous cough?
AB  - Little is known about the mechanisms which generate cough in patients with
      diffuse parenchymal lung disease. This article outlines some of the possible
      mechanisms which cause cough in patients with idiopathic pulmonary fibrosis
      (IPF). It goes on to discuss what is currently known about the enhanced cough
      reflex which afflicts patients with this condition, and describes recent evidence
      for enhanced expression of neurotrophins in the lungs of these patients.
      Preliminary data indicating that corticosteroids can reduce the cough reflex
      response to capsaicin and substance P in IPF offer hope that more specific
      therapies may be developed in the future.

PMID- 15564075
TI  - Acute and chronic cough.
AB  - Individuals are generally content to self-medicate for acute cough. It is only
      when the cough becomes persistent that they seek medical assistance. It is not
      known why patients cough in association with an acute upper respiratory tract
      infection (URTI), although interest has focused on how viruses may influence
      airway sensory nerve function and contribute to heightened cough reflex
      sensitivity. Why some patients develop a persistent cough following a viral URTI
      is also unclear. Much more is known about the causes and aggravants of chronic
      cough although there is no broad agreement as to the best way to manage such
      patients. Asthma, upper gastrointestinal dysfunction and rhinitis are frequently
      associated with chronic cough, although the impact of cough in suppurative lung
      disease and interstitial lung fibrosis is rarely considered. The development of
      effective treatments for cough remains a challenge and will require co-operation
      between clinicians, scientists and the pharmaceutical industry.

PMID- 15564076
TI  - Ionotropic and metabotropic receptor mediated airway sensory nerve activation.
AB  - There are several receptors capable of inducing activating generator potentials
      in cough-associated afferent terminals in the airways. The chemical receptors
      leading to generator potentials can be subclassified into ionotropic and
      metabotropic types. An ionotropic receptor has an agonist-binding domain, and
      also serves directly as an ion channel that is opened upon binding of the
      agonist. Examples of ionotropic receptors found in airway sensory nerve terminals
      include receptors for serotonin (5-HT3 receptors), ATP (P2X receptors),
      acetylcholine (nicotinic receptors), receptors for capsaicin and related
      vanilloids (TRPV1 receptors), and acid receptors (acid sensing ion channels).
      Afferent nerve terminals can also be depolarized via activation of metabotropic
      or G-protein coupled receptors (GPCRs). Among the GPCRs that can lead to
      activation of airway afferent fibers include bradykinin B2 and adenosine A1
      receptors. The signaling events leading to GPCR-mediated membrane depolarization
      are more complex than that seen with ionotropic receptors. The GPCR-mediated
      effects are thought to occur through classical second messenger systems such as
      activation of phospholipase C. This may lead to membrane depolarization through
      interaction with specific ionotropic receptors (such as TRPV1) and/or various
      types of calcium activated channels.

PMID- 15564077
TI  - Sensory regulation of the cough reflex.
AB  - Coughing is a highly coordinated reflex that serves to protect the airways from a
      variety of potentially harmful stimuli. However, in airways disease the cough
      reflex threshold is lowered and coughing can become exaggerated and
      inappropriate. Excessive coughing not only affects an individual's quality of
      life, but may contribute to the pathology of the disease. Understanding the
      neural components of the cough reflex is essential for establishing new
      treatments for cough disorders. This review will summarize the current
      understanding of the afferent neural pathways mediating cough, including how
      interactions between airway afferent nerve fibre subtypes may modulate the cough
      reflex pathway and underlie the manifestation of cough disorders.

PMID- 15564078
TI  - Production of reflex cough by brainstem respiratory networks.
AB  - Delineation of neural mechanisms involved in reflex cough is essential for
      understanding its many physiological and clinical complexities, and the
      development of more desirable antitussive agents. Brainstem networks that
      generate and modulate the breathing pattern are also involved in producing the
      motor patterns during reflex cough. Neurones of the ventrolateral medulla
      respiratory pattern generator mutually interact with neural networks in the pons,
      medulla and cerebellum to form a larger dynamic network. This paper discusses
      evidence from our laboratory and others supporting the involvement of the nucleus
      tractus solitarii, midline raphe nuclei and lateral tegmental field in the
      medulla, and the pontine respiratory group and cerebellum in the production of
      reflex cough. Gaps in our knowledge are identified to stimulate further research
      on this complicated issue.

PMID- 15564079
TI  - Laryngeal inputs in defensive airway reflexes in humans.
AB  - Stimulation of laryngeal receptors is the natural starting point of defensive
      airway reflexes including the cough reflex, expiration reflex, spasmodic panting,
      and apnoea with laryngospasm. Although several different types of laryngeal
      receptors have been reported, the laryngeal irritant receptors are considered to
      play the most essential role in elicitation of defensive airway reflexes. Based
      on the knowledge that the laryngeal irritant receptors are stimulated by water
      solutions lacking chloride anions, we have developed an experimental method to
      elicit defensive airway reflexes with a direct instillation of distilled water
      onto the laryngeal mucosa in humans. Using this experimental method, we studied
      the characteristics of defensive airway reflexes in lightly anaesthetized
      patients with multiple system atrophy (MSA). The reflex responses to water
      stimulation observed in these patients were characterized by apnoea with
      laryngospasm while the cough reflex was never elicited. Endoscopic images of the
      larynx in these patients were also characterized by laryngeal oedema. Considering
      the pathological changes occurring in the central nervous system and the
      laryngeal mucosa, it is possible that the defensive airway reflexes may be
      modified by central and/or peripheral mechanisms in patients with MSA.

PMID- 15564080
TI  - Experimental models and mechanisms of enhanced coughing.
AB  - Enhanced coughing can be produced in a variety of animal models, including the
      guinea pig, cat, dog and pig. Typically, airway inflammation has been produced by
      sensitization, exposure to cigarette smoke, sulphur dioxide or angiotensin
      converting enzyme inhibitors. In some of these models, inflammatory mediators
      such as bradykinin and tachykinins have been shown to contribute to the enhanced
      coughing. While most of these studies have focussed on peripheral mechanisms,
      increases in central excitability of the cough reflex have been shown to occur as
      a result of airway inflammation. As such, we propose that enhanced coughing in
      pathological conditions is the result of plastic changes in both peripheral and
      central neural elements. Furthermore, we present a modified model of the
      neurogenesis of cough that takes into account peripheral and central plasticity
      induced by mediators of inflammation.

PMID- 15564081
TI  - Mechanisms of acute cough.
AB  - The physiology of cough has become one of the primary focuses of recent research
      into the cough reflex. Peripherally, interest in differentiating subtypes of
      airway afferent fibres to determine their contributions to the cough reflex has
      led to the discovery of an RAR-fibre subtype that responds exclusively to tussive
      stimuli in the anaesthetized guinea pig and has been hypothesized to initiate the
      normal defensive cough reflex. Further investigations have begun to more fully
      differentiate these and other afferent fibre types pharmacologically. Centrally,
      investigations into the involvement of respiratory networks and gating mechanisms
      in the cough reflex have contributed to our understanding of the control of
      cough. Pathological changes in the cough reflex resulting from disease are also
      beginning to be elucidated. Further research in this area should lead to a more
      complete understanding of cough and a more rational approach to its treatment.

PMID- 15564082
TI  - Cough in chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) most commonly complain
      of cough, production of phlegm and breathlessness. The cough reflex sensitivity
      is heightened compared with that in healthy volunteers and is similar to that in
      subjects with asthma. The degree of airflow obstruction does not predict cough
      reflex sensitivity or objective cough counts, implying an independent process.
      Objective cough rates seem to be relatively low in COPD, despite frequent
      reporting of the symptom by patients. The relative contribution of cough to
      disability in COPD seems to be small, if assessed by subjective reporting.
      Effective treatments for cough in COPD have not yet been identified. Improved
      outcome measures of cough, a better understanding of the mechanisms underlying
      cough, and the importance of cough to patients is required to progress in this
      field.

PMID- 15564083
TI  - Cough and asthma.
AB  - Cough variant asthma and the closely related corticosteroid responsive cough
      syndromes eosinophilic bronchitis and atopic cough are common causes of chronic
      cough. The diagnosis is often not overt but detailed investigation of airway
      responsiveness and airway inflammation can be helpful. Cough variant asthma,
      eosinophilic bronchitis and atopic cough are all associated with eosinophilic
      airway inflammation, which is similar to that seen in non-cough predominant
      asthma. However, evidence of activated mast cells and increased concentrations of
      mast cell products appears to be confined to the conditions associated with
      cough, suggesting a role for mast cell degranulation in the superficial airway
      structures in the pathogenesis of cough. Cough variant asthma is typically
      corticosteroid responsive; leukotriene antagonists and antihistamines also help.
      Further study of this interesting asthma variant may increase our understanding
      of the relationship between airway inflammation and airway dysfunction.

PMID- 15564084
TI  - Cough and gastro-oesophageal reflux disease.

PMID- 15564085
TI  - Cough in cancer patients.

PMID- 15564086
TI  - Cough in children with congenital central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome (CCHS) is defined as failure of the
      chemical (autonomic) control of breathing causing alveolar hypoventilation in the
      absence of pulmonary, cardiac, neuromuscular or patent brainstem lesions.
      Hypoventilation is predominant in non-rapid-eye-movement sleep, during which
      breathing is primarily under chemical control. Failure of the central integration
      of chemosensory inputs is proposed as the putative defect. A genetic basis for
      CCHS is supported by lines of evidence. In some diseases of the central nervous
      system there is more or less complete depression of the cough reflex, whereas
      spontaneous ventilation is generally preserved. Little is known regarding cough
      in CCHS patients. Parents consistently report that their children cough
      'normally' during airway infections; in contrast, experimental lines of evidence
      suggest that CCHS children lack a cough response following inhalation of a
      tussigenic agent. Although several factors may account for the discrepancy, the
      possibility of a weakened or even absent cough reflex remains to be fully
      ascertained. Conceivably, a defective cough reflex, in conjunction with the well
      established lack of perception of respiratory discomfort, might result in an
      increased risk of potentially serious respiratory complications in CCHS patients.

PMID- 15564087
TI  - What do we know about how humans cough?
AB  - We review the evidence that activation of the cerebral cortex can lead to
      movements of the vocal folds and possibly to cough. Electrical stimulation of the
      motor cortex can cause movements of the vocal folds and vocalizatioin, but cough
      has not been reported. The motor pathways are via the nucleus ambiguous and
      possibly the nucleus retroambuigualis in the brainstem. In humans, activation of
      the cerebral cortex by transcranial magnetic stimulation can cause motor
      potentials in the intrinsic laryngeal muscles and corresponding surface
      potentials. The relationships between the cortical sensation related to cough,
      the voluntary control of cough and the involvement of reflex pathways remain to
      be clarified.

PMID- 15564088
TI  - Idiopathic cough, prevalence and underlying mechanisms.
AB  - A number of authors have reported a significant percentage of patients whose
      cause of cough remains undetermined despite a systematic evaluation as
      recommended in a number of International Guidelines. This subset of patients,
      which may be regarded as having an idiopathic cough, are often female and of peri
      or postmenopausal age. Sex hormones may influence the cough reflex in disease or
      contribute to the chronic lymphocytic airway inflammation seen in some cases and
      to the association with organ specific autoimmune disease reported. This paper
      seeks to investigate some of the possible causes of idiopathic cough.

PMID- 15564089
TI  - Airway inflammation and remodelling changes in patients with chronic cough: do
      they tell us about the cause of cough?
AB  - Airway mucosal changes have been reported in chronic cough. In cough variant
      asthma and in eosinophilic bronchitis, there is evidence of eosinophil
      infiltration and sub-basement membrane thickening. In non-asthmatic cough, an
      increase of bronchoalveolar mast cells, mucosal mononuclear cells, and epithelial
      shedding have been reported. In a more recent study, evidence of airway wall
      remodelling has been observed in both asthmatic and non-asthmatic cough, such as
      an increase in sub-basement membrane thickness, goblet cell area, vascularity and
      vessel size. Smooth muscle area was increased in non-asthmatic coughers.
      Heightened cough sensitivity in non-asthmatic coughers was related to the degree
      of goblet cell hyperplasia and epithelial shedding. Cough reflex may be
      heightened by increased production of growth factors that might be further
      enhanced by the physical effects of cough on the airways. Mast cells may
      participate in the cough pathophysiology through release of growth factors as
      well as tussive mediators. Changes in the airway wall mucosa and epithelium may
      be important in the pathogenesis of cough receptor sensitization.

PMID- 15564090
TI  - Plasticity of vagal afferent fibres mediating cough.
AB  - Increased sensitivity of cough pathways has been demonstrated in numerous
      studies. The underlying mechanisms of this sensitization are largely unknown;
      however, a burgeoning body of evidence suggests that vagal primary afferent
      neurones that innervate the airways are likely to be involved. This plasticity
      includes changes in anatomy, neurochemistry and function. PGE2 is an example of
      an inflammatory mediator that increases responsiveness to tussive stimuli.
      Electrophysiological studies of neurone cell bodies isolated from afferent
      ganglia have revealed that prostanoids modulate the function of a variety of
      distinct ion channels including those that carry TTX-insensitive voltage-gated
      sodium currents, slow post-spike hyperpolarizations and a hyperpolarization
      activated cation current. Mediator-induced modulation of the function of various
      voltage-gated currents operating at the peripheral terminals of airway afferent
      neurons would probably influence input from the airways into the central nervous
      system and contribute to the urge to cough and increased responsiveness to
      tussive stimuli.

PMID- 15564091
TI  - Plasticity of central mechanisms for cough.
AB  - Cough is associated with plasticity of putative cough afferent fibres, but
      whether plasticity in the brainstem network contributes is less well understood.
      A key site in the CNS network is the nucleus tractus solitarius (NTS), the first
      synaptic contact of the primary afferent fibres. We sought to develop a conscious
      guinea pig model to detect enhanced cough, to focus on the NTS as a potential
      site for plasticity, and to test a role for substance P in the NTS since the
      neuropeptide has been implicated in plasticity of the vagal afferent fibres.
      Guinea pigs were exposed to second-hand tobacco smoke (SHS) or filtered air (FA)
      from 1-6 weeks of age. At 5 weeks, cannulae were implanted in the NTS. At 6
      weeks, either vehicle or a neurokinin 1 (NK-1) receptor antagonist was injected
      into the NTS of the conscious guinea pigs who were then exposed to citric acid
      aerosol. SHS exposure significantly enhanced citric acid-induced cough (56%,
      P<0.05), an effect attenuated by NTS NK-1 receptor blockade (P<0.05). The
      findings suggest that one possible mechanism for plasticity in cough is related
      to substance P effects in the NTS. Future studies will be required to investigate
      the possible mechanisms underlying the role of substance P as well as other
      mechanisms in generating SHS-induced cough.

PMID- 15564092
TI  - Potential new cough therapies.
AB  - Cough is among the most common complaints for which patients seek medical
      attention. Consequently, enormous expenditures are made worldwide on prescription
      and non-prescription cough remedies. Multiple prospective studies have shown that
      specific antitussive therapy aimed at the underlying aetiology of cough is highly
      successful. The greatest current need therefore is for more effective nonspecific
      antitussive therapy, whose purpose is to suppress the cough reflex and provide
      symptomatic relief regardless of the underlying mechanism. Such therapy is
      particularly required for prolonged cough following upper respiratory tract
      infection, cough whose underlying aetiology is not easily treated, and idiopathic
      cough. Many areas of inquiry are currently ongoing that may lead to the
      development of novel and effective antitussive drugs.

PMID- 15564093
TI  - Mechanisms of chronic cough.
AB  - Chronic and uncontrollable cough is one of the most common and debilitating
      symptoms found in patients with chronic airway diseases. The physical trauma and
      stresses of chronic cough on the airway mucosa and respiratory muscles can
      further worsen the deteriorating process of the airway diseases. The articles
      presented in this section focus primarily on the effect of chronic cough on the
      cell structure and protective function of the airway mucosa, the mechanisms
      underlying the hypersensitivity of chronic cough, and new target areas for
      antitussive drug development. A major emphasis has been placed on the neuronal
      plasticity found at the peripheral and central sites of the neural pathway
      mediating the cough reflex, and its potential role in the development of chronic
      cough is discussed. A number of new and important questions concerning the
      physiological and pharmacological mechanisms underlying chronic cough have
      emerged in these presentations. Further studies are required to answer these
      questions, which should bring a better understanding of the pathogenic mechanisms
      of chronic cough and lead to the development of new therapeutic strategies.

PMID- 15564094
TI  - Physiological down-regulation of cough.

PMID- 15564096
TI  - Acute and chronic cough.

PMID- 15564097
TI  - Satisfaction survey in general hospital personnel involved in blood transfusion:
      implementation of the ISO 9001: 2000 standard.
AB  - As part of its policy of constant quality improvement, Etablissement francais du
      sang (EFS) des pays de la Loire (Pays de la Loire Regional Blood Transfusion
      Centre) carried out a satisfaction survey among the hospital personnel involved
      in prescribing and using immunohaematological tests and labile blood products
      (LBP). The polling tool selected by agreement between the Saint Nazaire's
      hospital management and Quality Assurance (QA) Department was a questionnaire
      that permitted item rating and free commentary. It addressed the personnel's
      perception of the quality of erythrocyte immunohaematological (EIH) testing and
      of the products administered, as well as their perception of the quality of
      communications with the local EFS. The questionnaire was sent to 26 physicians
      and 32 senior nurses in 15 hospital departments. The reply rate was 60% and
      expressed an 85% overall satisfaction level. Dissatisfaction causes were more
      specifically analysed, the main one involving LBP distribution in emergency
      situations. A joint undertaking by the EFS and the hospital led to the
      implementation of corrective measures, including the writing and implementation
      of a common standard operating procedure for emergency transfusion management.
      The results obtained demonstrated the feasibility of this type of survey and the
      interest, to a blood transfusion centre and the hospital personnel involved in
      transfusion, of assessing their very own perception of service quality.

PMID- 15564098
TI  - [Achievement quality evaluation of pretransfusion bedside test].
AB  - As far as transfusions accidents are concerned, immunological causes are
      frequent. Pretransfusion Bedside Compatibility Tests (PBCT) are the last chance
      to avoid them. However low data are disponible on the quality their realisation
      is achieved. The aim of the study is to evaluate the quality level of achievement
      of these tests, in HIA Laveran Hospital (Marseille Armees, France). During 13
      months, from november 2001 to december 2002, we systematically analysed PBCT
      after use (analysis rate 91%). Three kinds of errors have been noticed: Technical
      errors, understanding errors and both. Overall mistake rate was 10.4% (1632 tests
      analysed). In the same time, a complementary formation was dispensed to users
      responsible of misfits. This formation was successful, decreasing the overall
      mistake rate from 22.8% (november 2001) to 10.7% (december 2002). This study is
      an evidence of the importance to evaluate achievement quality of PBCT and shows
      how efficient can be simple correction methods.

PMID- 15564099
TI  - [Efficiency of hepatitis C virus screening before and after blood transfusion].
AB  - Efficiency of a viral hepatitis C screening strategy before and after blood
      transfusion has to be evaluated. METHODS: Four screening strategies were
      virtually applied to the population of transfused patients at Rouen University
      Hospital during 1996 and then compared : the first without any systematic HCV
      screening test; the second with systematic testing both before and 3 months after
      transfusion; the third with systematic testing both before and 6 months after
      transfusion ; the last defined as systematic testing before transfusion only. The
      efficacy (i.e. number of positive tests), the efficiency (i.e. average cost per
      positive test) and the marginal costs of moving from a strategy to another one
      were assessed using decision analysis. RESULTS: The efficacy of systematic
      screening test before transfusion only (361 per positive test), systematic
      testing both before and three months after (523 per positive test) or six months
      after (488 per positive test) transfusion was similar, but the efficacy of the
      strategy without any systematic screening test (385 per positive test) was lower.
      The systematization of screening test both before, and three months, or 6 months
      after transfusion lead to a marginal cost of 619 , and 559 per positive test
      respectively. The systematization of testing before transfusion only lead to a
      marginal cost of 343 per positive test. Adding systematic testing after
      transfusion lead to a marginal cost of 5824 per positive test. CONCLUSION:
      Systematic screening tests before transfusion only can be considered as the most
      efficient strategy.

PMID- 15564100
TI  - [Quality-assessment of the transfusion record in a Paris hospital in 2003].
AB  - AIM OF THE STUDY: To realize a clinical audit of the quality of the transfusion
      record in the Pitie-Salpetriere hospital (Paris, France). MATERIALS AND METHODS:
      Using a 1/10th poll method, a representative sample of patients who underwent a
      blood transfusion in the first quarter of 2002 in the hospital was constituted.
      Data were collected in the clinical units using a standardized questionnaire.
      RESULTS: Sample size was 247 patients for whom 219 patient files and 207
      transfusion record (94.5%, CI(95%) [91.5-97.5]) were found. Transfusion record
      did not follow the patient in 29 cases (59%). Among the transfusion record, 82.1%
      contained a copy of the prescription for blood components, 89.8% a transfusion
      card, 93.2% a traceability note, 100% an ABO group card, 98.6% an antibody
      screen, 57.1% a pretransfusion viral testing results and 7,8% a copy of the
      posttransfusion biology testing. Traceability of pre and posttransfusion patient
      information was respectively 6,8% and 21,1%. Presence of pretransfusion testing
      results, patient information and posttransfusion prescription was significantly
      higher in the surgical and intensive care units' patient files than in the
      medical units (resp. P = 0.018; 0.02 and 0.017). CONCLUSION: Difficulties in the
      transmission of transfusion records when patients change clinical unit or are
      rehospitalized and a lack of knowledge concerning the elements which are
      mandatory to be kept in the transfusion record could explain the results of this
      study. This assessment is fully in line with the process of transfusion security
      improvement. In order to promote the quality of the transfusion record, new
      recommendations and tools were elaborated following this study.

PMID- 15564101
TI  - [Survival after blood transfusion: a study at Rouen university hospital].
AB  - The aim of this study was to estimate short term survival rate after blood
      transfusion according to various criteria. PATIENTS AND METHODS: Patients
      admitted and transfused from January, 1 until June, 30 1996 at Rouen university
      hospital were retrospectively included, and their status (alive or dead) was
      determined. The characteristics of patients admitted and transfused were compared
      to the overall population of inpatients. Independent factors associated with
      mortality six months after blood transfusion were evaluated using Cox model.
      RESULTS: During the study period, 1887 patients were transfused. These patients
      were older, more often admitted in surgical or in intensive care units, and had a
      longer duration of stay, than the overall inpatients population. The survival
      rate at six months in transfused patients was 76.1%. Mortality rate at six months
      was independently higher in patients aged 75 and older, in men, in patients
      admitted in intensive care units, or transfused with homologous fresh-frozen
      plasma or packed platelet blood cells. Mortality rate was lower in patients who
      underwent a surgical procedure, in children under 16, and in patients whose stay
      was classified in "Circulatory system disorders", "Musculoskeletal system and
      connective tissues disorders or trauma", or "Injuries, allergy or poisoning".
      CONCLUSION: In this study implemented in a teaching hospital inpatients receiving
      blood transfusion, the survival was mainly associated with the severity and
      characteristics of the diseases requiring transfusion.

PMID- 15564102
TI  - [Checking of blood product in hospital].
AB  - Delivery of blood products includes: checking of the parcel destination address,
      checking of the parcel itself and of its contents. Preserving the blood product
      in a depot imposes an agreement of storage between the hospital and the French
      national blood service to be established. In addition, authorisation of storage
      from the administrative head of department is required. The "Etablissement
      francais du sang" must be partner of the process.

PMID- 15564103
TI  - [Some ideas for taking in charge accidental blood exposures in the French blood
      establishment].
AB  - Accidental blood exposures (ABE) are one of the most important problems when
      talking about industrial accidents in institutions such as the French blood
      establishment. The three major viruses concerned by these exposures are the AIDS
      virus (HIV) and Hepatitis viruses: HIV; HCV and HBV. There are universal
      prevention's ways for the three viruses, a vaccination way for Hepatitis B, and a
      way of prophylaxis, using triple therapy, for HIV. For the best taking in charge
      of ABE, it is important to be able to assess quickly the risk, using serology of
      the source (blood donor or patient), to be able, if needed, to treat with triple
      therapy, within two hours, members of staff exposed to HIV, and to be able to
      follow-up these persons in the next four months. French blood establishment has
      very certainly a critical role in this strategy of prevention, following-up and,
      above all, taking in charge in the very first therapeutic instants.

PMID- 15564104
TI  - [Transportation in blood transfusion].
AB  - Equipment including vehicles, packaging, cool packs and temperature indicators
      must be valid, well maintained and checked. Documentation, operating
      instructions, transportation forms, contracts and conventions must be established
      and regularly updated in accordance with regulation. Staff must get consistent,
      specific and qualified training.

PMID- 15564105
TI  - [The responsibility of the physician prescriber of blood products].
AB  - Blood transfusion presents mainly virological, bacteriological,
      immunohaematological and volemic risks; with the latter two particularly
      concerning health establishment employees. This article tackles the physician's
      responsibility in blood transfusion. Taking into account the regulations that
      surround the activity, prescribing physicians must know and put into action the
      relative requirements in their practises in order to avoid taking on its
      responsibility, or that of the health establishment in which they work, as any
      lack of respect for the rules and regulations could result in being held liable
      for any side affects suffered by the patient. The article has the objective of
      identifying the main regulation requirements in order to control them despite a
      difficult environment, from the point of view of patients' rights regarding the
      benefits and the consequences of transfusion. These requirements focus mainly on
      information and patient consent, the prescription of blood products as well post
      transfusion information and the follow-up care. Proof of respect for these rule
      requirements must be available for each of these aspects.

PMID- 15564107
TI  - Exploring structure-function relationships in neocortical networks by means of
      neuromodelling techniques.
AB  - Determining the neuronal architecture underlying certain visual functions is of
      fundamental importance for understanding how sensory processing is implemented in
      the brain. The wealth of anatomical, physiological and biophysical data that is
      being currently acquired on the neocortex could be used to constrain its
      functional architecture. However, given the intrinsic complexity and diversity of
      the data, it is difficult to provide a comprehensive framework to use these data
      in order to characterize structure-function relationships. Here, we discuss the
      use of biophysically plausible models of dynamics of neuronal networks,
      constructed to reflect the known properties of neocortical connectivity and
      modularity, as a tool to bring together anatomy and physiology. We illustrate the
      utility and rationale of the neuro-dynamics modelling approach by considering
      recent studies on the relationship between functional structure of the visual
      cortex and its response timing, and on the cellular and network origin of
      neuronal oscillations in the gamma frequency range. We also critically discuss
      how an interaction between theory and experiments could help this approach to
      become directly relevant for clinical applications.

PMID- 15564108
TI  - Neurocomputational models of the remote effects of focal brain damage.
AB  - Sudden localized brain damage, such as occurs in stroke, produces neurological
      deficits directly attributable to the damaged site. In addition, other clinical
      deficits occur due to secondary "remote" effects that functionally impair the
      remaining intact brain regions (e.g., due to their sudden disconnection from the
      damaged area), a phenomenon known as diaschisis. The underlying mechanisms of
      these remote effects, particularly those involving interactions between the left
      and right cerebral hemispheres, have proven somewhat difficult to understand in
      the context of current theories of hemispheric specialization. This article
      describes some recent neurocomputational models done in the author's research
      group that try to explain diaschisis qualitatively. These studies show that both
      specialization and diaschisis can be accounted for with a single model of
      hemispheric interactions. Further, the results suggest that left-right
      subcortical influences may be much more important in influencing hemispheric
      specialization than is generally recognized.

PMID- 15564109
TI  - Models of the subthalamic nucleus. The importance of intranuclear connectivity.
AB  - A coherent set of models is presented that provide novel and testable predictions
      about the functional role of the subthalamic nucleus (STN) in the basal ganglia.
      The STN is emerging as an important target for novel therapeutic strategies for
      the alleviation of Parkinsonian type symptoms [Lancet 345 (1995) 91; Science 249
      (1990) 1436]. Computational and mathematical models based on the properties of
      the STN and its interactions are reviewed. These models focus on core anatomical
      and physiological data that span many levels. By assessing models of anatomy,
      dynamic network models, and a detailed model of a recent pharmacological
      experiment, we can expose the primary modes of STN function and highlight their
      underlying properties. We show that the presence of functional interactions
      between STN projection neurons is critical in defining its behaviour and how it
      interacts with other basal ganglia nuclei. Pulses or switch-like activity
      patterns emerge in the models as a consequence of these local interactions.
      Furthermore, the models demonstrate that this behaviour can break down under
      abnormal conditions resulting in low frequency bursting oscillations. Such
      oscillations may play a role in symptoms of Parkinson's disease.

PMID- 15564110
TI  - A biased competition based neurodynamical model of visual neglect.
AB  - On the computational basis of a neurodynamical cortical model, we investigate a
      specific top-down visual cognitive impairment in brain-damaged patients known as
      visual spatial neglect. The computational cortical model accounts the
      neurodynamics underlying selective visual attention, is based on the "biased
      competition hypothesis" and structured in several network modules which can be
      related with the different areas of the dorsal and ventral path of the visual
      cortex. Spatial and object attention are accomplished by a multiplicative gain
      control that emerges dynamically through intercortical mutual biased coupling. By
      damaging the model in different ways, a variety of dysfunctions associated with
      visual neglect can be simulated and explained as disruption of specific
      subsystems. Essentially, the damage destabilizes the underlying intra- and
      intermodular mutually biased neurodynamical competition that macroscopically
      yields the functional deficits observed in visual neglect patients. In
      particular, we are able to explain the asymmetrical effect of spatial cueing on
      neglect, and the phenomenon of extinction in the framework of visual search.

PMID- 15564111
TI  - Consciousness monitoring using near-infrared spectroscopy (NIRS) during high +Gz
      exposures.
AB  - The relationship between human consciousness and oxygen saturation (rSO(2)) in
      cerebral tissue under high +Gz stress was non-invasively monitored by near
      infrared multiple wavelength spectroscopy (NIRS). We studied the drop in rSO(2)
      levels in human subjects during exposure to various head-to-foot acceleration
      (+Gz) profiles. These profiles included sustained +Gz plateaus and repeated short
      duration +Gz pulses of varying duration. The end point in this study was +Gz
      induced loss of consciousness (G-LOC). The rSO(2) levels under normal
      (asymptomatic), almost loss of consciousness (A-LOC) and G-LOC conditions were
      recorded. Correlations among decrease in rSO(2), +Gz pulse duration, +Gz stress
      level and incapacitation time (ICAP) after G-LOC were also investigated. It was
      found that once rSO(2) fell to a certain level, G-LOC occurred. This threshold
      was repeatable and independent of the +Gz level or duration. It was also observed
      that the total ICAP after G-LOC was dependent on the length of time that rSO(2)
      remained below the G-LOC threshold level, i.e. the longer the rSO(2) level
      remained below the G-LOC induction level, the longer the subject remained
      unconscious. These results may prove to be useful in designing closed loop
      control systems for personal protective gear for pilots of high performance
      aircraft.

PMID- 15564112
TI  - CFD modeling of blood flow following coil embolization of aneurysms.
AB  - In case of coil embolization of a giant or a multilobular aneurysm, it is
      difficult to fill an aneurysm sac completely with coils, therefore, partial
      blocking of an aneurysm sac is inevitable. Blood flow characteristics, which may
      influence embolization process of an aneurysm, are affected by the locations of
      coils for partially blocked aneurysms. Blood flow fields inside an aneurysm are
      also influenced by the geometry of a parent vessel. In order to suggest the coil
      locations effective for aneurysm embolization, the blood flow fields of lateral
      aneurysm models were analyzed for different coil locations and parent vessel
      geometries. Flow rate into an aneurysm sac from a parent vessel (inflow rate) and
      wall shear stress were also calculated. Inflow rates were smaller and low wall
      shear regions were larger in the distal neck blocked model comparing to the dome
      blocked models. In the distal neck blocked model, inflow volume was smaller by
      31% (straight parent vessel model) and 34% (curved parent vessel model) comparing
      to other models. The time averaged values of normalized low wall shear regions
      were 4% and 12% greater in the distal neck blocked models with a straight and a
      curved parent vessel, respectively. Since smaller inflow and low wall shear
      stress provide hemodynamic environment promoting thrombus embolization, distal
      neck should be the effective coil location for aneurysm embolization.

PMID- 15564113
TI  - Detecting variability of internal carotid arterial Doppler signals by Lyapunov
      exponents.
AB  - The new method presented in this study was directly based on the consideration
      that internal carotid arterial Doppler signals are chaotic signals. This
      consideration was tested successfully using the nonlinear dynamics tools, like
      the computation of Lyapunov exponents. Multilayer perceptron neural network
      (MLPNN) architecture was formulated and used as a basis for detecting
      variabilities such as stenosis and occlusion in the physical state of internal
      carotid arterial Doppler signals. The computed Lyapunov exponents of the internal
      carotid arterial Doppler signals were used as inputs of the MLPNN. Receiver
      operating characteristic (ROC) curve was used to assess the performance of the
      detection process. The internal carotid arterial Doppler signals were classified
      with the accuracy varying from 94.87% to 97.44%. The results confirmed that the
      proposed MLPNN trained with Levenberg-Marquardt algorithm has potential in
      detecting stenosis and occlusion in internal carotid arteries.

PMID- 15564114
TI  - Nonlinear-analysis of human sleep EEG using detrended fluctuation analysis.
AB  - Quantification of the fractal scaling properties of human sleep EEG dynamics was
      sought and each normal sleep stage was compared with that of sleep apnea. The
      fractal scaling exponents that quantify power-law correlations were computed
      using detrended fluctuation analysis. Six healthy subjects, aged 30-35 years,
      participated and six recordings of the apnea were acquired from MIT/BIH
      polysomnography database. The data were 8-h baseline recordings (23:00-07:00 h).
      The EEG signals from the C4-A1 derivation were acquired with a resolution of 250
      Hz. The sleep stages were visually scored for 30 s epochs, according to the
      criteria of Rechtschaffen and Kales. The mean scaling exponents increased from
      the awake stage to stages 1, 2 and 3-4, but decreased during rapid eye movement
      (REM) sleep. The scaling exponents of the apnea were lower than those of the
      healthy subject for all the stages. The scaling exponents could be attributed to
      the fractal nature of EEG, which would be more appropriate for describing the
      complexity of EEG due to its assumption of non-stationarity.

PMID- 15564115
TI  - Multibody dynamic simulation of knee contact mechanics.
AB  - Multibody dynamic musculoskeletal models capable of predicting muscle forces and
      joint contact pressures simultaneously would be valuable for studying clinical
      issues related to knee joint degeneration and restoration. Current three
      dimensional multibody knee models are either quasi-static with deformable contact
      or dynamic with rigid contact. This study proposes a computationally efficient
      methodology for combining multibody dynamic simulation methods with a deformable
      contact knee model. The methodology requires preparation of the articular surface
      geometry, development of efficient methods to calculate distances between contact
      surfaces, implementation of an efficient contact solver that accounts for the
      unique characteristics of human joints, and specification of an application
      programming interface for integration with any multibody dynamic simulation
      environment. The current implementation accommodates natural or artificial
      tibiofemoral joint models, small or large strain contact models, and linear or
      nonlinear material models. Applications are presented for static analysis (via
      dynamic simulation) of a natural knee model created from MRI and CT data and
      dynamic simulation of an artificial knee model produced from manufacturer's CAD
      data. Small and large strain natural knee static analyses required 1 min of CPU
      time and predicted similar contact conditions except for peak pressure, which was
      higher for the large strain model. Linear and nonlinear artificial knee dynamic
      simulations required 10 min of CPU time and predicted similar contact force and
      torque but different contact pressures, which were lower for the nonlinear model
      due to increased contact area. This methodology provides an important step toward
      the realization of dynamic musculoskeletal models that can predict in vivo knee
      joint motion and loading simultaneously.

PMID- 15564116
TI  - Total body centre of mass displacement estimated using ground reactions during
      transitory motor tasks: application to step ascent.
AB  - A double integration technique is presented that estimates whole body centre of
      mass (CoM) displacement from signals of a single force platform, compensating for
      the drift and low frequency noise inherent in the signals. The technique is
      composed of two different integration techniques, which may also be used
      separately, and is applied to transitory motor tasks with known initial and final
      conditions such as step ascent and descent, single step, etc. First, the lowest
      frequencies within the force platform signals and considered not to be associated
      with actual movement are filtered out. Second, a regular and a time-reversed
      double integration are performed and weighted against each other. The technique's
      accuracy was assessed using computer generated force platform signals that were
      artificially perturbed. Experimental data were used to compare the estimated CoM
      displacement to that obtained from a regular double integration and from
      segmental analysis performed on stereophotogrammetric data. It was shown that the
      proposed technique's CoM displacement estimates were more repeatable and up to
      50% more accurate than those of a regular double integration. Moreover, the CoM
      displacement estimated using a single force platform and the proposed technique
      was found to be not statistically different from that obtained with more
      demanding measurement and processing techniques such as stereophotogrammetry and
      segmental analysis.

PMID- 15564117
TI  - Using the absorbed power method to evaluate effectiveness of vibration absorption
      of selected seat cushions during manual wheelchair propulsion.
AB  - Although wheelchair users are frequently subjected to oscillatory and shock
      vibrations, little research has been conducted to assess the whole-body vibration
      exposure of wheelchair users. The purpose of this study was to determine if
      selected wheelchair cushions alter potentially harmful whole-body vibrations
      transferred to wheelchair users. Thirty-two participants, who use wheelchairs as
      their primary mode of mobility, contributed to this study. Four of the most
      commonly prescribed wheelchair cushions were selected. Participants were asked to
      propel their wheelchair over a simulated activities of daily living (ADL) course
      while acceleration and force data were recorded. A repeated measures ANOVA showed
      no significant differences between the different cushions for the total averaged
      absorbed power (p = 0.190), the 50 mm curb drop (p = 0.234), or the rumble strip
      (p = 0.143). A repeated measure ANOVA for the peak curb drop absorbed power
      revealed a significant difference in the cushions (p = 0.043). The cushions that
      were most effective in this testing appear to be the Invacare Pindot and the
      Varilite Solo. Not only did those cushions appear to have the lowest values much
      of the time but also they did not display the highest values. When comparing
      results from a similar study, absorbed power appears to be as effective in
      determining vibration effects in the time domain as the methods in the ISO 2631
      Standard.

PMID- 15564118
TI  - Improved tibial cutting accuracy in knee arthroplasty.
AB  - Initial stability and development of long-term fixation for cementless tibial
      components at the knee both depend on the accuracy of fit between implanted
      components and prepared bone surfaces. Tibial surfaces prepared for total knee
      replacement with conventional saw-blades and guides were shown by Toksvig-Larsen
      to vary by over 2 mm, from a flat surface at the point of maximum variation, and
      all points varied with a standard deviation of up to 0.4 mm. Surface cutting
      errors are caused by flexion of the saw-blade and blade angulation from the ideal
      alignment, due to poor guidance or control by the saw-block or guide. Most
      conventional knee instrumentation relies on flat surface or slotted cutting
      blocks, constraining the moving saw-blade against one or two guide surfaces.
      Improved cutting action was achieved by constraining the saw from the pivot point
      of the blade, and controlling motion of this constraint with parallel action
      slides. Using this saw-guide and an improved saw-blade, tibial cuts were made in
      mock arthroplasty procedures on twenty four cadaveric tibiae in mortuo. Analysis
      of Variance and Tukey's HSD test showed that the improved saw technique yielded
      significantly better flatness (p < 0.03) and greatly improved roughness (p <
      0.0005).

PMID- 15564119
TI  - Compartmentalization of the splicing machinery in plant cell nuclei.
AB  - The cell nucleus is a membrane-surrounded organelle that contains numerous
      compartments in addition to chromatin. Compartmentalization of the nucleus is now
      accepted as an important feature for the organization of nuclear processes and
      for gene expression. Recent studies on nuclear organization of splicing factors
      in plant cells provide insights into the compartmentalization of the plant cell
      nuclei and conservation of nuclear compartments between plants and metazoans.

PMID- 15564120
TI  - Unveiling the molecular arms race between two conflicting genomes in cytoplasmic
      male sterility?
AB  - Cytoplasmic male sterility can be thought of as the product of a genetic conflict
      between two genomes that have different modes of inheritance. Male sterilizing
      factors, generally encoded by chimeric mitochondrial genes, can be down-regulated
      by specific nuclear restorer genes. The recent cloning of a restorer gene in rice
      and its comparison with restorer genes cloned in petunia and radish could be
      regarded as the beginning of a general molecular scenario in this peculiar arms
      race.

PMID- 15564121
TI  - Controversy remains: regulation of pH gradient across the thylakoid membrane.

PMID- 15564123
TI  - Biosynthesis of L-ascorbic acid in plants: new pathways for an old antioxidant.
AB  - The biosynthetic pathway of L-ascorbic acid (vitamin C) in plants has been
      established for several years. However, recent reports describe alternative
      pathways, revealing a more complex picture of L-ascorbic acid biosynthesis than
      had been expected. GDP-L-gulose and myo-inositol are proposed as new
      intermediates in L-ascorbic acid biosynthesis, indicating that part of the animal
      pathway might also be operating in plants. Enzymatic studies on the GDP-mannose-
      3',5'-epimerase and L-galactono-1,4-lactone dehydrogenase suggest that they are
      important regulatory steps for L-ascorbic acid biosynthesis.

PMID- 15564124
TI  - PIN and AUX/LAX proteins: their role in auxin accumulation.
AB  - There is mounting evidence that plant tissues specialized for auxin transport
      coincide with local maxima in the auxin concentration. This result is difficult
      to reconcile with the traditional model of auxin transport, which relies on high
      levels of auxin efflux carrier expression. Because transporting cells maintain
      high levels of auxin efflux, one naively expects a depletion of auxin relative to
      surrounding tissues. Here I use a computer model of auxin transport in a
      background of parenchyma cells to evaluate the possible roles of the PIN and
      AUX/LAX families of putative auxin carriers in auxin accumulation. I describe two
      effective accumulation strategies and review the evidence that these strategies
      are used by plants.

PMID- 15564125
TI  - Cell shape development in plants.
AB  - The shape of a plant cell has long been the cornerstone of diverse areas of plant
      research but it is only recently that molecular-genetic and cell-biological tools
      have been effectively combined for dissecting plant cell morphogenesis. Increased
      understanding of the polar growth characteristics of model cell types, the
      availability of many morphological mutants and significant advances in
      fluorescent-protein-aided live-cell visualization have provided the major impetus
      for these analyses. The cytoskeleton and its regulators have emerged as essential
      components of the scaffold involved in fabricating plant cell shape. In this
      article, I collate information from recent discoveries to derive a simple
      cytoskeleton-based operational framework for plant cell morphogenesis.

PMID- 15564126
TI  - Networks of transcription factors with roles in environmental stress response.
AB  - Genome-wide transcriptome analyses have identified hundreds of genes encoding
      transcription factors that are induced or repressed by a range of environmental
      stresses. Their complex expression patterns suggest that stress tolerance and
      resistance are controlled at the transcriptional level by a complicated gene
      regulatory network. The next steps towards understanding stress biology at the
      systems level are reconstructing the network and then verifying the roles these
      transcription factors play in the network.

PMID- 15564127
TI  - Can less yield more? Is reducing nutrient input into the environment compatible
      with maintaining crop production?
AB  - Plant scientists have long recognized the need to develop crops that absorb and
      use nutrients more efficiently. Two approaches have been used to increase
      nutrient use efficiency (NUE) in crop plants. The first involves both traditional
      breeding and marker-assisted selection in an attempt to identify the genes
      involved. The second uses novel gene constructs designed to improve specific
      aspects of NUE. Here, we discuss some recent developments in the genetic
      manipulation of NUE in crop plants and argue that an improved understanding of
      the transition between nitrogen assimilation and nitrogen recycling will be
      important in applying this technology to increasing crop yields. Moreover, we
      emphasize the need to combine genetic and transgenic approaches to make
      significant improvements in NUE.

PMID- 15564128
TI  - Function and regulation of plant invertases: sweet sensations.
AB  - The disaccharide sucrose and the cleavage products glucose and fructose are the
      central molecules for carbohydrate translocation, metabolism and sensing in
      higher plants. Invertases mediate the hydrolytic cleavage of sucrose into the
      hexose monomers. Plants possess three types of invertases, which are located in
      the apoplast, the cytoplasm and the vacuole, respectively. It has become evident
      that extracellular and vacuolar invertase isoenzymes are key metabolic enzymes
      that are involved in various aspects of the plant life cycle and the response of
      the plant to environmental stimuli because their substrates and reaction products
      are both nutrients and signal molecules. Invertases, alone or in combination with
      plant hormones, can regulate many aspects of the growth and development of plants
      from gene expression to long-distance nutrient allocation and are involved in
      regulating carbohydrate partitioning, developmental processes, hormone responses
      and biotic and abiotic interactions.

PMID- 15564130
TI  - Adeno-associated virus and the development of adeno-associated virus vectors: a
      historical perspective.

PMID- 15564131
TI  - Dual therapeutic utility of proteasome modulating agents for pharmaco-gene
      therapy of the cystic fibrosis airway.
AB  - Pharmacologic- and gene-based therapies have historically been developed as two
      independent therapeutic platforms for cystic fibrosis (CF) lung disease.
      Inhibition of the dysregulated epithelial Na channel (ENaC) is one pharmacologic
      approach to enhance airway clearance in CF. We investigated pharmacologic
      approaches to enhance CFTR gene delivery with recombinant adeno-associated virus
      (rAAV) and identified compounds that significantly improved viral transduction
      while simultaneously inhibiting ENaC activity through an unrelated mechanism.
      Treatment of human CF airway epithelia with proteasome modulating agents (LLnL
      and doxorubicin) at the time of rAAV2 or rAAV2/5 infection dramatically enhanced
      CFTR gene delivery and correction of CFTR-mediated short-circuit currents.
      Surprisingly, these agents also facilitated long-term (15-day) functional
      inhibition of ENaC currents independent of CFTR vector administration. Inhibition
      of ENaC activity was predominantly attributed to a doxorubicin-dependent decrease
      in gamma-ENaC subunit mRNA expression and an increase in gamma-ENaC promoter
      methylation. This is the first report to describe the identification of compounds
      with dual therapeutic action that are able to enhance the efficacy of CFTR gene
      therapy to the airway while simultaneously ameliorating primary aspects of CF
      disease pathophysiology. The identification of such compounds mark a new area for
      drug development, not only for CF, but also for other gene therapy disease
      targets.

PMID- 15564132
TI  - Intrapleural administration of a serotype 5 adeno-associated virus coding for
      alpha1-antitrypsin mediates persistent, high lung and serum levels of alpha1
      antitrypsin.
AB  - alpha1-Antitrypsin (alpha1AT) is a serine proteinase inhibitor that protects the
      lung from degradation by neutrophil proteases. In alpha1AT deficiency, an
      autosomal recessive disorder resulting from mutations in the alpha1AT (approved
      symbol SERPINA1) gene, serum alpha1AT levels of < 570 microg/ml are associated
      with development of emphysema. Adeno-associated virus (AAV) serotype 2 (AAV2)
      vectors expressing alpha1AT administered intramuscularly or intravenously mediate
      sustained serum levels of alpha1AT in experimental animals. Since the lung is
      only 2% of the body weight, AAV vector delivery to the muscle or liver is
      inefficient, as most of the alpha1AT does not reach the lung. The present study
      evaluates AAV2- and AAV5-mediated delivery of human alpha1AT (halpha1AT) to
      C57BL/6 mice using the intrapleural space as a platform for local production of
      alpha1AT. Intrapleural administration of either an AAV5-halpha1AT or an AAV2
      halpha1AT vector achieves higher lung and serum levels of alpha1AT than
      intramuscular delivery. AAV5-mediated serum and lung alpha1AT levels were 10-fold
      higher than those achieved by AAV2 delivery via either route. The diaphragm,
      lung, and heart are the major sites of transgene expression following
      intrapleural administration of an AAV5 reporter vector. At 40 weeks
      postadministration, intrapleural administration of the AAV5-halpha1AT vector
      mediated serum alpha1AT levels of 900 +/- 50 microg/ml, 1.6-fold higher than the
      accepted therapeutic level of 570 microg/ml. In the context that the pleura is a
      safe site for administration, intrapleural administration using AAV5 vectors may
      represent an attractive gene therapy strategy for alpha1AT deficiency in humans.

PMID- 15564133
TI  - Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin
      rearrangement.
AB  - The use of membrane-permeable peptides as carrier vectors for the intracellular
      delivery of various proteins and macromolecules for modifying cellular function
      is well documented. Arginine-rich peptides, including those derived from human
      immunodeficiency virus 1 Tat protein, are among the representative classes of
      these vectors. The internalization mechanism of these vector peptides and their
      protein conjugates was previously regarded as separate from endocytosis, but more
      recent reevaluations have concluded that endocytosis is involved in their
      internalization. In this report, we show that the uptake of octa-arginine (R8)
      peptide by HeLa cells was significantly suppressed by the macropinocytosis
      inhibitor ethylisopropylamiloride (EIPA) and the F-actin polymerization inhibitor
      cytochalasin D, suggesting a role for macropinocytosis in the uptake of the
      peptide. In agreement with this we observed that treatment of the cells with R8
      peptide induced significant rearrangement of the actin cytoskeleton. The
      internalization efficiency and contribution of macropinocytosis were also
      observed to have a dependency on the chain length of the oligoarginine peptides.
      Uptake of penetratin, another representative peptide carrier, was less sensitive
      to EIPA and penetratin did not have such distinct effects on actin localization.
      The above observations suggest that penetratin and R8 peptides have distinct
      internalization mechanisms.

PMID- 15564134
TI  - A human single-chain Fv intrabody blocks aberrant cellular effects of
      overexpressed alpha-synuclein.
AB  - alpha-Synuclein (alpha-syn) has been identified as the major component of Lewy
      bodies that characterize neurodegenerative synucleinopathies, including
      Parkinson's disease. Overexpression of alpha-syn, and prefibrillar alpha-syn
      oligomers, has been implicated in these pathologies; therefore, prevention of
      prefibril accumulation, and inhibition of other aberrant effects of overexpressed
      alpha-syn, could provide novel treatments. Here, we have selected a human single
      chan Fv (scFv) antibody, D10, that binds human monomeric wild-type alpha-syn. We
      demonstrate, by retargeting assays and coimmunoprecipitation, that the D10 scFv
      is a specific and efficient intracellular antibody (intrabody). By transfecting
      the D10 scFv gene into an HEK 293 cell line that overexpresses wild-type alpha
      syn, we show that the D10 intrabody stabilizes detergent-soluble monomeric alpha
      syn and inhibits the formation of detergent-insoluble high-molecular-weight alpha
      syn species. In addition, the D10 intrabody ameliorates the decreased cell
      adhesion that characterizes the alpha-syn-overexpressing cells. Given the
      important role of alpha-syn pathology, and the facility with which intrabodies
      can be further engineered in vitro, anti-alpha-syn intrabodies may represent
      novel molecular therapeutics for synucleinopathies, with implications for other
      neurodegenerative disorders caused by misfolded accumulated proteins.

PMID- 15564135
TI  - Characterization of intraperitoneal, orthotopic, and metastatic xenograft models
      of human ovarian cancer.
AB  - Improvement of ovarian cancer patient outcome requires well-characterized animal
      models in which to evaluate novel therapeutics. Xenograft models are frequently
      used, but with little discussion of disease histology. The objectives of this
      study were to inject 11 ovarian cancer cell lines intraperitoneally (ip), and a
      subset intrabursally (ib; orthotopic), into nude mice and to analyze the
      resulting pathologies. Eight of 11 lines injected ip formed tumors within 3
      months at variable rates with the following histological subtype distribution:
      one endometrioid, one serous, one clear cell, and five undifferentiated. Only
      mice injected with A2780-cp cells presented with ovarian-specific metastases (11
      of 88), and the survival time of these animals was significantly shorter, which
      may be attributed to the higher proliferation rate as determined by Ki67
      positivity. Additional analysis of the influence of the ovarian microenvironment
      on cell characteristics was conducted with ib injection of two cell lines (OVCA
      429 and ES-2). The site of injection did not affect the tumor histology, the
      effect on proliferation was cell-type dependent, and the tumor take rate (cell
      survival) was negatively affected for OVCA 429 cells. The animal models described
      herein represent histologically distinct models of both early and late stage
      ovarian cancer useful for evaluation of therapeutics.

PMID- 15564136
TI  - Prolonged survival of mice with multiple liver metastases of human colon cancer
      by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A
      expressed by CEA promoter.
AB  - Liver is the most preferential site for metastasis of colon cancer. We, in the
      present study, constructed a self-replicable adenovirus in which E1A is driven by
      a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and
      examined its effects on multiple metastases of a human colon cancer cell in a
      mouse xenograft model. We first showed effective replication of the virus in
      various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent
      lysis of the infected cells in vitro. We then demonstrated that a single
      intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete
      regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we
      demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl)
      through the tail vein to nude mice, which 1 week prior had been inoculated with
      tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent
      multiple metastases in the liver, effectively suppressed the metastasis
      formation. The mean survival time of the treated mice was significantly longer
      than that of the controls. Thus, the systemic administration of AdCEAp/Rep was
      considered to be effective on multiple liver metastases of CEA-positive colon
      cancer in a xenograft model.

PMID- 15564137
TI  - Targeting prostate cancer with conditionally replicative adenovirus using PSMA
      enhancer.
AB  - Prostate cancer is the second most commonly diagnosed cancer in men and accounts
      for significant mortality and morbidity in the United States. Initially androgen
      dependent, prostate cancer ultimately becomes androgen-independent, which makes
      the disease extremely difficult to cure. In this study, we examined the use of
      conditionally replication-competent adenovirus for the treatment of hormone
      independent prostate cancer. We utilized PSME, an enhancer element for prostate
      specific PSMA expression, to control viral E1A protein expression and achieve
      exclusive virus replication in prostate. Western blotting confirmed that PSME
      mediated high E1A protein expression in PSMA-positive, androgen-independent
      prostate cancer cells (C4-2 and CWR22rv), but was much less active in PSMA
      negative cancer cells (PC-3 and A549). Consistent with E1A protein expression,
      the recombinant adenovirus Ad5-PSME-E1a replicated in C4-2 and CWR22rv almost as
      efficiently as wild type with low levels of androgen, but its replication was
      significantly attenuated in PSMA-negative cells. In the in vitro killing assay,
      Ad5-PSME-E1a lysed all C4-2 and CWR22rv cells 5 days after infection, with
      minimal effect on PSMA-negative cells. In addition, injections of 1.7 x 10(8)
      plaque-forming units in a CWR22rv xenograft model in nude mice induced
      significant tumor growth delay, with a substantial necrotic area. These studies
      suggest that PSME-driven replication-competent adenovirus may be a new
      therapeutic modality for prostate cancer patients after hormone ablation therapy.

PMID- 15564138
TI  - Adenovirus-mediated FLT1-targeted proapoptotic gene therapy of human prostate
      cancer.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is of
      particular interest in the development of prostate carcinoma therapeutics as it
      preferentially induces apoptosis of tumor cells. To employ adenoviral vectors for
      highly efficient and specific TRAIL gene transfer into cancer cells could
      overcome some potential problems for recombinant TRAIL. The vascular endothelial
      growth factor receptor FLT-1 is involved in regulation of angiogenesis and tumor
      growth, invasion, and metastasis of prostate carcinoma. FLT-1 expression is
      observed in both tumor endothelial cells and prostate cancer cells. We developed
      an adenoviral vector encoding the TRAIL gene under control of the FLT1 promoter
      (AdFlt-TRAIL), which produced endothelial and prostate cancer cell death. The
      combination of ionizing radiation and adenovirus-driven TRAIL expression overcame
      human prostate cancer cell resistance to TRAIL. Furthermore, in vivo
      administration of AdFlt-TRAIL at the site of tumor growth in combination with
      radiation treatment produced significant suppression of the growth of DU145 human
      prostate tumor xenografts in athymic nude mice. Our results suggest that specific
      TRAIL delivery employing the FLT1 promoter can effectively inhibit tumor growth
      and demonstrate the advantage of combination radiotherapy and gene therapy for
      the treatment of prostate cancer.

PMID- 15564139
TI  - Inflammatory and anti-glioma effects of an adenovirus expressing human soluble
      Fms-like tyrosine kinase 3 ligand (hsFlt3L): treatment with hsFlt3L inhibits
      intracranial glioma progression.
AB  - Glioblastoma multiforme is an intracranial tumor that has very poor prognosis.
      Patients usually succumb to their disease 6 to 12 months after they are diagnosed
      despite very aggressive treatment modalities. We tested the efficacy of a potent
      differentiation and proliferation factor for the professional antigen-presenting
      dendritic cells (DCs), i.e., Flt3L, for its potential role as a novel therapy for
      gliomas. We investigated the ability of recombinant adenoviral vectors encoding
      human soluble Flt3L (hsFlt3L) to improve the survival of Lewis rats bearing
      intracranial syngeneic CNS-1 gliomas. We show that RAdhsFlt3L can improve
      survival in a dose-dependent manner. Seventy percent of rats survive when treated
      with 8 x 10(7) pfu RAdhsFlt3L (P < 0.0005). In addition we demonstrate in both
      naive Lewis rats and C57BL/6 mice the presence of increased numbers of cells
      bearing DC markers (OX62 and MHCII, in rats, or CD11C, 33D1, MHCII, and F4/80,
      but not DEC205, in mice) in sites of brain delivery of RAdhsFlt3L. These results
      show that expression of hsFlt3L in the brain leads to the presence of cells
      displaying DC markers. We demonstrate that treatment with hsFlt3L leads to
      inhibition of tumor growth and significantly increased life span of animals
      implanted with syngeneic CNS-1 glioma cells. Animals that had survived for long
      periods, i.e., 6 months, had eliminated the implanted tumors after
      neuropathological analysis; on the other hand, some of the 3-month survivors
      still appeared to harbor brain tumors. Our results have profound implications for
      immune-mediated brain tumor therapy and also suggest the ability to recruit DC
      like cells within the brain parenchyma in response to the local expression of
      Flt3L from adenoviral vectors.

PMID- 15564140
TI  - Bystander activity of Ad-mda7: human MDA-7 protein kills melanoma cells via an IL
      20 receptor-dependent but STAT3-independent mechanism.
AB  - The melanoma differentiation-associated gene-7 (mda-7/IL24) is a unique member of
      the IL-10 family of cytokines, with ubiquitous tumor cell proapoptotic activity.
      Transduction of tumor or normal cells with the mda-7 gene results in secretion of
      glycosylated MDA-7 protein. Recent data indicate that secreted MDA-7 protein
      functions as a pro-Th1 cytokine and as a potent antiangiogenic molecule. MDA-7
      protein binds two distinct type II cytokine heterodimeric receptor complexes, IL
      20R1/IL-20R2 (type 1 IL-20R) and IL-22R1/IL-20R2 (type 2 IL-20R). In this study
      we analyzed the activity of glycosylated secreted MDA-7 against human melanoma
      cells. MDA-7 protein induces phosphorylation and nuclear translocation of STAT3
      in melanoma cells via both type 1 and type 2 IL-20R. MDA-7 induces dose-dependent
      cell death in melanoma tumor cells. MDA-7 receptor engagement results in up
      regulation of BAX and subsequent apoptosis induction; this effect is mediated by
      STAT3-independent signaling. Additional IL-10 family members (IL-10, -19, -20,
      and -22) also activate STAT3; however, these ligands do not activate death
      pathways in melanoma. In normal cells, MDA-7 can bind to its cognate receptors
      and induce phosphorylation of STAT3, without cytotoxic sequelae. This study
      defines a tumor-selective cytotoxic bystander role for secreted MDA-7 protein and
      identifies a novel receptor-mediated, STAT3-independent, and PKR-independent
      death pathway.

PMID- 15564141
TI  - IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+
      cells while maintaining in vivo lymphoid potential.
AB  - To improve maintenance and gene transfer of human lymphoid progenitors for
      clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we
      investigated several gene transfer protocols using various stem cell-enriched
      sources. The lymphoid differentiation potential was measured by an in vitro
      clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo
      culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7
      substantially increased the yield of transduced bone marrow (BM) CD34(+) cells
      purified from ADA-SCID patients or healthy donors, compared to T/F/S alone.
      Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in
      vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient
      transduction of B and NK cell progenitors. Under these optimized conditions
      transduced CD34(+) cells were efficiently engrafted into SCID-hu mice and gave
      rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid
      reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was
      included in a gene therapy clinical trial for ADA-SCID, resulting in long-term
      engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34(+) cells
      obtained from one patient 4 and 11 months after gene therapy were capable of
      repopulating the lymphoid compartment of SCID-hu hosts.

PMID- 15564142
TI  - Retroviral transduction of hematopoietic cells differentiated from human
      embryonic stem cell-derived CD45(neg)PFV hemogenic precursors.
AB  - Human embryonic stem cells (hESCs) provide a unique opportunity to study
      molecular mechanisms that regulate specification of the hematopoietic lineage in
      the human. Exploitation of this model using transgenic strategies depends on the
      ability to target cells of the hematopoietic lineage effectively and establish
      stable transgene expression. Here, a recently defined subpopulation of
      endothelial-like precursors derived from hESCs that is exclusively responsible
      for hematopoietic cell fate (CD45(neg)PFV) is shown to express GALVR-1 receptor
      and be efficiently transduced with GALV-pseudotyped retrovirus. Retroviral
      transduction, measured by enhanced green fluorescent protein, of hESC-derived
      CD45(+) cells differentiated from isolated CD45(neg)PFV precursors was 26.5 +/-
      13% with 5.6 +/- 4% of these cells coexpressing CD34. An average of 17.5% of
      clonogenic hematopoietic progenitors derived from CD45(neg)PFV precursors
      expressed the retroviral transgene. Addition of serum to cultures after
      retroviral exposure supported transgene expression in resulting hematopoietic
      cells derived from hemogenic CD45(neg)PFV precursors. Our study represents the
      first report to demonstrate that retroviral transduction systems, similar to
      those used currently in clinical gene therapy protocols, are capable of efficient
      transduction of hematopoietic progenitors derived from hESCs.

PMID- 15564143
TI  - Axonal transport of recombinant baculovirus vectors.
AB  - Targeted gene delivery to neurons is crucial to effective gene therapy of
      neurodegenerative diseases. Several types of viral gene vectors may target
      neurons through retrograde axonal transport to somas of projection neurons after
      viral internalization at axon terminal fields. In this report we demonstrate for
      the first time that recombinant baculovirus vectors could migrate by axonal
      transport to cell bodies, resulting in transgene expression in projection
      neurons. After stereotaxic injection of Cy3-labeled baculovirus vectors into the
      rat striatum, retrograde axonal transport of the baculovirus vectors was observed
      along the corticostriatal pathway and nigrostriatal pathway. Furthermore, after
      intra-vitreous body injection, anterograde axonal transport and transsynaptic
      transport of the virus particles were observed in defined connections of the
      visual system, from the retina to the optic nerve, the lateral geniculate body,
      the superior colliculus, and the primary visual cortex. PCR analysis confirmed
      the existence of transported viral DNA in the tissue samples collected from
      projection fields. Driven by a neuron-specific promoter, transgene expression
      from the recombinant baculovirus vectors was detectable in target regions remote
      from injection sites. The attributes of baculovirus vectors in the bidirectional
      axonal transport and transneuronal transport in neural circuits of the central
      nervous system could be utilized for targeted gene delivery.

PMID- 15564144
TI  - Metallothionein gene therapy for chemical-induced liver fibrosis in mice.
AB  - Liver fibrogenesis resulting from a diversity of pathological changes involves a
      disturbance in mineral, in particular zinc, homeostasis. The present study was
      undertaken to determine whether gene therapy with metallothionein (MT), a small
      protein critically involved in the regulation of zinc homeostasis, can improve
      the recovery of liver fibrosis in a mouse model. Wild-type (WT) mice treated with
      carbon tetrachloride in corn oil twice a week at 1 ml/kg for 4 weeks developed a
      reversible liver fibrosis upon removal of the chemical, correlating with a high
      level of hepatic MT; but those treated for 8 weeks developed an irreversible
      liver fibrosis along with low levels of hepatic MT. The same carbon tetrachloride
      treatment for 4 weeks resulted in an irreversible liver fibrosis in MT-knockout
      (MT-KO) mice. Adenoviral delivery of the human MT-II gene (approved symbol MT2A)
      through intravenous injection reversed the fibrosis along with increased
      hepatocyte regeneration within 3 days in both WT and MT-KO mice with irreversible
      fibrosis. The MT elevation was associated with increased activities of
      collagenases in the liver. This study indicates that MT makes a critical
      contribution to the reversal of chemical-induced hepatic fibrosis and has
      therapeutic potential for patients with certain liver fibrosis.

PMID- 15564145
TI  - Recombinant adenovirus vectors activate the alternative complement pathway,
      leading to the binding of human complement protein C3 independent of anti-ad
      antibodies.
AB  - Recombinant adenoviruses are one of the most common gene transfer vectors
      utilized in human clinical trials, but it is also clear that systemic
      administration of this virus will be met by host innate and adaptive antiviral
      immune responses. One element of innate immunity is the complement system, a
      group of proteins that has evolved to rapidly recognize foreign microbes and
      viruses and to clear them from the circulatory system prior to their gaining
      entry to vulnerable host cells. Excessive complement activation can initiate or
      propagate a number of deleterious inflammatory responses, by release of potent
      cytokines and anaphylatoxins and/or by direct cellular toxicity. These reactions
      can progress rapidly and are factors important in serious complications,
      including the systemic inflammatory response syndrome and the adult respiratory
      distress syndrome.

PMID- 15564146
TI  - A rational regulatory approach for positron emission tomography imaging probes:
      from "first in man" to NDA approval and reimbursement.
AB  - We propose a new regulatory approach for positron emission tomography (PET)
      molecular imaging probes, essential tools in today's medicine. Even though the
      focus of this paper is on positron-emitting labeled probes, it is also justified
      to extend this proposed regulatory approach to other diagnostic nuclear medicine
      radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular
      imaging probes would be placed in a "no significant risk" category, similar to
      that category for devices in current Food and Drug Administration (FDA)
      regulations, based on overwhelming scientific evidence that demonstrates their
      faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research
      Committee (RDRC) will oversee all diagnostic research with these probes. The
      newly defined RDRC should approve "first in man" use; supervise a broader
      spectrum of diagnostic research protocols, including those looking to demonstrate
      initial efficacy, as well as multicenter clinical trials and the use of molecular
      imaging probes as a screening tool in drug discovery. The current investigational
      new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when
      a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval
      (i.e., NDA) will be sought. The review will be done by a newly constituted
      Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the
      professional societies, who would provide a binding assessment of the adequacy of
      the safety and efficacy data. When the RDAC recommends its diagnostic use on
      scientific and medical grounds, the molecular imaging probe becomes FDA approved.
      After a molecular imaging probe is approved for a diagnostic indication, the
      existing mechanism to seek reimbursement will be utilized; and (4) the FDA would
      retain its direct oversight function for traditional manufacturers engaged in
      commercial distribution of the approved diagnostic molecular imaging probes
      (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP)
      requirements. With abbreviated and more appropriate regulations, new PET
      molecular imaging probes for diagnostic use would be then rapidly incorporated
      into the mainstream diagnostic medicine. Equally importantly, this approach would
      facilitate the use of molecular imaging in drug discovery and development, which
      would substantially reduce the costs and time required to bring new therapeutic
      drugs to market.

PMID- 15564147
TI  - Benzodiazepine-resistant "brown fat" pattern in positron emission tomography: two
      case reports of resolution with temperature control.
AB  - PURPOSE: Supraclavicular uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) on
      positron emission tomography (PET) scan is attributed to lymph node, muscle, or
      brown fat activity. Differentiation between physiological or pathological
      etiologies is necessary. Benzodiazepine premedication to reduce physiological
      uptake has been attempted with variable success. A relationship between brown-fat
      FDG uptake and cold temperature has also been established. To our knowledge, no
      case reports or studies have been published to demonstrate whether controlling
      the temperature can alter the physiological uptake in these regions. PROCEDURES:
      Two teenage female patients with these patterns on PET scans performed with oral
      benzodiazepine administration underwent repeat imaging with temperature
      controlled environment settings. RESULTS: Resolution of supraclavicular FDG
      uptake with temperature control in two patients in whom benzodiazepine had no
      prior effect. CONCLUSION: Although the exact mechanism remains unknown, we
      propose that the control of temperature reduces the metabolism of glucose by
      brown fat. Further studies are warranted to confirm the above observations, and,
      if confirmed, to determine the most efficient and effective use of temperature
      control to minimize supraclavicular and axillary FDG uptake.

PMID- 15564148
TI  - Synthesis and characterization of a potent, selective, radiolabeled substance-P
      antagonist for NK1 receptor quantitation: ([18F]SPA-RQ).
AB  - PURPOSE: To develop and characterize a radiolabelled Substance-P antagonist
      useful for quantitation of neurokinin-1 receptors in the brain via PET imaging.
      PROCEDURE: [18F]SPA-RQ (Substance-P antagonist - receptor quantifier) was
      synthesized in good yield and high specific activity by alkylation of a BOC
      protected phenolate anion using [18F]bromofluoromethane. Removal of the BOC
      protecting group with trifluoroacetic acid gave [18F]SPA-RQ. RESULTS: SPA-RQ has
      high affinity for human, rhesus monkey and guinea pig NK1 receptors (h-IC50=67
      pM) and has a log P value of 1.8. Biodistribution studies in guinea pig showed
      that this tracer penetrates the blood-brain barrier and selectively labels NK1
      receptors in the striatum and cortex. CONCLUSION: [18F]SPA-RQ is a potent, high
      affinity Substance-P antagonist that can be conveniently labeled with high
      specific activity using [18F]fluoromethylbromide. This tracer is a useful tool
      for noninvasive imaging of central NK1 receptors.

PMID- 15564149
TI  - Noninvasive of adenovirus tumor retargeting in living subjects by a soluble
      adenovirus receptor-epidermal growth factor (sCAR-EGF) fusion protein.
AB  - PURPOSE: To demonstrate that non-invasive bioluminescent imaging can monitor
      restricted expression from a nonreplicating adenovirus in which the
      cyclooxygenase-2 (COX-2) promoter drives firefly luciferase. PROCEDURES:
      Adenovirus in which the COX-2 promoter drives the firefly luciferase imaging gene
      was injected intratumorally into xenografts that express relatively low and
      relatively high levels of COX-2. Adenovirus that expresses Renilla Luciferase
      from the cytomegalovirus early promoter was co-injected, to normalize for
      injection, leakage, vascularization, etc. COX-2 restricted firefly luciferase and
      global Renilla Luciferase activities were measured by optical imaging techniques
      both in vivo and in isolated tissues. RESULTS: Dramatic reduction in hepatic
      luciferase expression after intravenous viral injection can be imaged non
      invasively in living animals. Following intratumoral injection, luciferase levels
      in tumor xenografts that express differing endogenous COX-2 levels reflect the
      luciferase levels observed when these cells are infected in cell culture.
      Essentially no luciferase expression is observed in liver following intratumoral
      injection. CONCLUSION: Both tissue restricted expression and transcriptional
      redirection to tumors expressing COX-2 can be imaged non-invasively following
      injection of Adenovirus expressing firefly luciferase from the COX-2 promoter.

PMID- 15564150
TI  - Noninvasive imaging of transcriptionally restricted transgene expression
      following intratumoral injection of an adenovirus in which the COX-2 promoter
      drives a reporter gene.
AB  - PURPOSE: To demonstrate the efficacy of repeated, non-invasive optical imaging of
      reporter gene expression in monitoring the ability of bi-specific recombinant
      molecules (i) to "transductionally untarget" adenovirus from Coxsackie and
      Adenovirus Receptor (CAR)-dependent infection of normal tissue and (ii) to
      "transductionally retarget" infection to specific target cells. PROCEDURES: sCAR
      EGF is a recombinant, bi-specific molecule containing the soluble portion of CAR
      fused to Epidermal Growth Factor. The sCAR moiety binds to the virus and blocks
      CAR-dependent adenovirus infection. The EGF moity binds to cellular EGF
      receptors. We used non-invasive optical imaging of firefly luciferase to
      repeatedly monitor, in living animals, the ability of sCAR-EGF (i) to
      "transductionally untarget" systemically administered Ad.CMVfLuc, an adenovirus
      that constitutively expresses luciferase, from normal tissues and (ii) to
      "transductionally redirect" adenovirus infection in mice to xenograft tumors that
      express elevated epidermal growth factor (EGF) receptor levels. RESULTS: Systemic
      injection of sCAR-EGF "coated" adenovirus expressing firefly luciferase from the
      CMV early promoter, reduces expression of the reporter gene in the liver and
      facilitates expression of the reporter gene in tumor xenografts expressing high
      levels of the EGF-receptor. CONCLUSION: Both liver "untargeting" and tumor
      "retargeting" of adenovirus by recombinant sCAR-EGF can be imaged non-invasively
      using a luciferase reporter gene.

PMID- 15564151
TI  - 2-Deoxy-2-[18F] fluoro-D-glucose uptake in intercostal respiratory muscles on
      positron emission tomography/computed tomography: smokers versus nonsmokers.
AB  - PURPOSE: The purpose of this study was to determine the frequency of 2-deoxy-2
      [18F]fluoro-D-glucose (FDG) uptake in the intercostal respiratory muscles (ICM)
      of smokers versus nonsmokers using positron emission tomography (PET).
      PROCEDURES: Ninety-six whole-body PET/computed tomography (CT) scans were
      retrospectively reviewed; 61 studies were from smokers and 35 from nonsmokers.
      The ICM uptake from the lung apices to the level of the carina was visually
      scored with respect to FDG intensity as follows: 0 = uptake less than or equal to
      lung uptake; 1 = greater than lung, but less than mediastinal blood pool; 2 =
      equal to mediastinal blood pool; and 3 = greater than mediastinal blood pool.
      RESULTS: In smokers, 30 out of 61 (49.2%) PET/CT scans had uptake that localized
      to ICM, compared to 3/35 (8.6%) studies in nonsmokers. Average ICM uptake was
      significantly different between smokers and nonsmokers (0.787 +/- 0.933 and 0.143
      +/- 0.494, respectively; P < 0.01). CONCLUSION: Increased FDG uptake in ICM is a
      physiologic pattern of uptake that is frequently seen and is more common in
      smokers.

PMID- 15564152
TI  - Comparison between 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography
      and positron emission tomography/computed tomography hardware fusion for staging
      of patients with lymphoma.
AB  - PURPOSE: 2-Deoxy-2-[18F]fluoro-D-Glucose positron emission tomography (FDG-PET)
      stages patients with Hodgkin's disease (HD) and Non-Hodgkin's lymphoma (NHL) with
      higher accuracy than computed tomography (CT). We sought to determine whether
      integrated (hardware) fused PET/CT imaging results in further improvements in
      staging accuracy. PROCEDURES: Seventy-three patients (age 51 +/- 17 years, 37
      female, 36 male) with HD (n = 20) or NHL (n = 53) undergoing staging were studied
      with an integrated PET/CT system. Image findings were verified by clinical follow
      up, additional imaging and when available, histology. RESULTS: Thirty-four of 73
      patients (46.5%) had evidence of disease and 39 were disease free as confirmed by
      clinical evaluation and follow-up for 41 +/- 22 weeks (n = 73), including biopsy
      (n = 26), and other imaging modalities (n = 52) when available. A discordant
      image interpretation between PET and PET/CT occurred in seven patients (10%).
      PET/CT correctly upstaged two and downstaged five patients. Overall staging was
      accurate in 93% with PET/CT and 84% with PET (P = 0.03). CONCLUSION: Lymphoma is
      staged with higher accuracy using PET/CT than PET alone.

PMID- 15564153
TI  - Randomized clinical surgical trials: are they really necessary?

PMID- 15564154
TI  - Conductive hearing loss and learning disabilities in children.

PMID- 15564155
TI  - Prevertebral soft tissue measurements in thyroid enlargement: the value of
      lateral neck radiographs.
AB  - BACKGROUND: Measurement of prevertebral soft tissue is commonly used to assess
      prevertebral abnormalities, such as retropharyngeal abscess or injury to the
      cervical spine. In the presence of goitres, the widened prevertebral tissue seen
      on plain lateral neck radiograph may be diagnostic of an enlarged tubercle of
      Zuckerkandl (ZT), which may be responsible for most pressure symptoms. The aim of
      this study was to substantiate the value of plain lateral neck radiographs in
      preoperative demonstration of enlarged ZT. METHODS: Fifty patients who underwent
      thyroid surgery between June and December 2000 were included in this prospective,
      non-randomized study. Measurements of prevertebral soft tissue were taken at C4,
      C5 and C6, and were correlated with the weight of goitres and the grades of
      changes in the ZTs. RESULTS: Of patients, 44% had large goitres weighing more
      than 100 g; 52% of ZTs were classified as grade 3. Of the large ZTs, 82% were
      associated with large goitres and, of these, 88% were associated with significant
      pressure symptoms. Prevertebral measurements were abnormal, particularly at C4,
      C5 and C6. The most promising predictor of the presence of an enlarged ZT is the
      measurement taken at C4 (p<0.05). The ratio of the prevertebral space to the
      vertebral body (PVS/VB) in grade 3 ZT was also increased at C4, C5 and C6.
      However, these ratios were not statistically significant. A measurement of
      prevertebral soft tissue, particularly at C4, greater than 16.5 mm correlates
      100% with an enlarged grade 3 ZT. CONCLUSIONS: The results of this study support
      the concept that the plain radiograph shows significant widening of the lateral
      neck in the presence of an enlarged ZT. Plain lateral radiography is a simple
      procedure that could provide valuable information for preoperative assessment of
      an enlarged ZT, particularly in patients with large goitres who have significant
      pressure symptoms.

PMID- 15564156
TI  - Management of iatrogenic facial nerve palsy and labyrinthine fistula in mastoid
      surgery.
AB  - A 6-year review of complications of mastoid surgery between June 1995 and June
      2001 revealed five cases with serious iatrogenic complications from mastoid
      surgery, of which four were facial nerve palsy and two were labyrinthine fistula.
      One of these patients had concomitant facial nerve palsy and labyrinthine
      fistula. There were two cases of complete facial nerve palsy (House Brackmann
      grade VI) and two cases of incomplete palsy (House Brackmann grades IV and V).
      The second genu was the site of injury in three of the four cases. Of the four
      cases with facial nerve palsy, two patients had full recovery (House Brackmann
      grade I), one recovered only to House Brackmann grade III, and one was lost to
      follow-up. Both patients with labyrinthine fistula had postoperative vertigo and
      profound sensorineural hearing loss. The site of iatrogenic fenestration was the
      lateral semicircular canal in both cases.

PMID- 15564157
TI  - Results of gastric pull-up reconstruction for pharyngolaryngo-oesophagectomy in
      advanced head and neck cancer and cervical oesophageal squamous cell carcinoma.
AB  - OBJECTIVE: To study long-term clinical swallowing function and survival outcome
      in head and neck and cervical oesophageal cancer patients who underwent
      pharyngolaryngo-oesophagectomy (PLE). METHODS: The clinical data of 48 patients
      who were treated with PLE were analysed. All patients had advanced disease, so
      the construction required a transposed stomach. Body weight and clinical
      swallowing function were evaluated postoperatively. The swallowing function was
      assessed at an interview concerning food ingestion and regurgitation. The
      survival group was studied using a Kaplan-Meier survival curve. RESULTS: Forty
      one cases of hypopharyngeal cancer and four cases of cervical oesophageal cancer
      were studied. In three cases (6%), hypopharyngeal and thoracic oesophageal
      squamous cell carcinoma occurred together. Most cases had good-to-fair results.
      The average body weight gain was increased after surgery. There was one hospital
      death. The most common complications were pulmonary (4%). Median survival was 27
      months. CONCLUSION: A pharyngogastric anastomosis after PLE can be performed with
      low morbidity and good swallowing function.

PMID- 15564158
TI  - Positive predictive value of BI-RADS categorization in an Asian population.
AB  - The Breast Imaging Reporting And Data System (BI-RADS) categorization of
      mammograms is useful in estimating the risk of malignancy, thereby guiding
      management decisions. However, in Asian women, in whom breast density is
      increased, the sensitivity of mammography is correspondingly lower. We sought to
      determine the positive predictive value of BI-RADS categorization for malignancy
      in our Asian population and, hence, its value in helping us to choose between the
      various modalities for breast biopsy. We retrospectively reviewed all patients
      with occult breast lesions detected on mammography or ultrasound who underwent
      needle-localization open breast biopsy (NLOB) in our institution over a 6-year
      period. There were 470 biopsies in 427 patients; 16% of lesions were malignant.
      The positive predictive value of BI-RADS 4 and 5 lesions for cancer was 0.27 and
      0.84, respectively. While most BI-RADS 5 mass lesions were invasive cancers, the
      majority of calcifications in this category were in situ carcinomas. We conclude
      that BI-RADS remains useful in aiding decision-making for biopsy in our Asian
      population. Based on positive predictive values, we recommend percutaneous breast
      biopsy for initial evaluation of lesions categorized as BI-RADS 4 or less. For BI
      RADS 5 lesions with microcalcifications, open surgical biopsy as a diagnostic and
      therapeutic procedure may be more appropriate. In the case of a BI-RADS 5 lesion
      associated with a mass, initial percutaneous biopsy may be useful for diagnosis,
      followed by a planned single-stage surgical procedure as necessary.

PMID- 15564159
TI  - Bronchoplastic and pulmonary arterioplastic procedures in the treatment of
      bronchogenic carcinoma.
AB  - OBJECTIVES: Bronchoplastic and pulmonary arterioplastic procedures have become
      increasingly popular in recent years as an alternative to pneumonectomy,
      especially for patients with compromised cardiopulmonary reserve. We reviewed our
      experience with the procedure to determine the operative technique, indication
      for the procedure and long-term results. METHODS: From January 1981 to December
      2000, 65 bronchoplasties, four pulmonary arterioplasties and three combined
      broncho-angioplasties were performed for bronchogenic carcinoma. RESULTS: Of the
      72 patients, 31 had stage I disease, 29 had stage II and 12 had stage III
      disease. One patient (1.4%) died of bilateral pneumonitis postoperatively.
      Atelectasis occurred in two patients (2.8%), empyema in one (1.4%), and bronchial
      fistula in one (1.4%). There were no bronchial stenoses after bronchoplastic
      procedures, and no vascular complications after angioplastic procedures. The 1-,
      3- and 5-year survival rates for the entire group were 86.0%, 47.0% and 29.8%,
      respectively. The difference in survival was significant between stage I and II
      disease (p=0.0001) and between stage I and III disease (p<0.0001), but not
      between stage II and III disease (p=0.0779). CONCLUSIONS: Bronchoplastic,
      pulmonary arterioplastic and broncho-angioplastic procedures can be performed
      safely. Bronchoplastic procedures offer patients with bronchogenic carcinoma a
      long-term result comparable to that with radical lung resection. Angioplastic and
      combined broncho-angioplastic procedures should only be used in patients who
      cannot tolerate pneumonectomy due to poor cardiopulmonary reserve.

PMID- 15564160
TI  - Mucosal neuroendocrine cell abnormalities in patients with chronic constipation.
AB  - OBJECTIVES: The aim of this study was to examine the distribution of
      neuroendocrine cells (NEC) in patients with chronic constipation (CC) as a means
      of establishing a relationship between pathology, symptomatology and treatment.
      METHODS: Rectal biopsy specimens from 43 patients with CC (aged 17-82 years) and
      20 age-matched normal controls were examined histopathologically using
      haematoxylin and eosin, and immunohistochemically using antibodies against
      chromogranin-A (Ch-A) and serotonin (5-HT) to detect NEC. The number of positive
      NEC per 70 crypts (CR) was counted and expressed as the ratio of NEC/CR. CC
      patients were divided into groups based on management, then compared using
      NEC/CR. RESULTS: CC was managed conservatively in 29 patients (group A) and
      invasively in 14. Of these 14, 10 had normal histology (group B) and four had
      typical histopathological signs of intestinal neuronal dysplasia (IND; group C).
      All control specimens were unremarkable. In controls, NEC/CR was 0.94+/-0.33 for
      Ch-A and 0.32+/-0.08 for 5-HT. In group A, NEC/CR was 2.23+/-0.13 for Ch-A and
      1.02+/-0.06 for 5-HT. In group B, it was 2.79+/-0.18 for Ch-A and 1.72+/-0.33 for
      5-HT. In group C, it was 3.12+/-0.22 for Ch-A and 2.32+/-0.14 for 5-HT. The
      increase in Ch-A and 5-HT immunoreactive cells in groups B and C compared with
      controls was greater (p<0.01, p<0.05) than the increase seen in group A compared
      with controls (p<0.01, p<0.05). CONCLUSIONS: These results demonstrate that
      increased numbers of NEC may play a role in the abnormal bowel function seen in
      CC, and may have some relationship with the development of giant submucosal
      ganglia in IND.

PMID- 15564161
TI  - Temporary ileostomy versus temporary colostomy: a meta-analysis of complications.
AB  - OBJECTIVE: To compare the complications of temporary diverting ileostomy with
      those of temporary colostomy for patients with colorectal diseases. METHODS: Two
      independent researchers conducted a systematic search for randomized controlled
      trials (RCTs) comparing temporary ileostomy with temporary colostomy in MEDLINE,
      the Cochrane database, evidence-based medicine reviews and the American College
      of Physicians journal club, as well as relevant reference lists in journal
      articles. Five RCTs were found and included in this meta-analysis. All
      complications were abstracted and compared between groups. All complications were
      also assessed using tests of statistical heterogeneity, pooling of risk ratios
      using Mantel-Haenszel fixed effects and DerSimonian and Laird random effects.
      Clinical heterogeneity was investigated by examining the methodology and
      selection of patients described in each trial. RESULTS: Temporary colostomy was
      significantly more likely to cause stoma complications in colorectal cancer
      patients undergoing elective resections, and also more likely to cause infectious
      and wound complications. Temporary ileostomy tended to cause more post-closure
      surgical complications. CONCLUSIONS: There is not yet a strong case for the
      superiority of one temporary diverting stoma over another for all colorectal
      patients. In this regard, a large, well-conducted RCT is still needed.

PMID- 15564163
TI  - Treatment of hepatic artery thrombosis after orthotopic liver transplantation.
AB  - OBJECTIVES: This study evaluated conservative treatment for delayed hepatic
      artery thrombosis after orthotopic liver transplantation (OLT). METHODS: Whole
      graft OLTs (n=108) and live donor liver transplants (LDLTs; n=140) were performed
      in 237 patients between October 1991 and July 2002. Seven episodes of hepatic
      artery thrombosis were identified in six patients. Among the six patients, three
      had received whole-graft OLT and three had received right-lobe LDLT. Treatment
      included retransplantation, thrombectomy plus thrombolysis, and conservative
      treatment of hepatic and biliary complications. RESULTS: Five patients survived
      after treatment. Among the three LDLT recipients who received conservative
      treatment, two had subsequent collateral formation and one had spontaneous
      recanalization of arterial inflow. Of the three recipients of whole-graft OLT,
      the first died because of hepatic failure and technically difficult
      retransplantation, the second had thrombectomy plus thrombolysis but had
      recurrence of thrombosis that spontaneously recannulated during conservative
      treatment, and the third patient had successful retransplantation for graft
      failure. CONCLUSION: In the absence of hepatic failure, conservative treatment
      appears to be effective for patients with hepatic artery thrombosis.
      Collateralization is more likely to develop after LDLT than after whole-graft
      OLT.

PMID- 15564165
TI  - Phased-array magnetic resonance imaging of the prostate with correlation to
      radical prostatectomy specimens: local experience.
AB  - PURPOSE: To evaluate local experience of phased-array magnetic resonance imaging
      (MRI) in the staging of locally advanced prostate carcinoma with comparison to
      clinical staging. METHODS: The study population was 21 patients who underwent
      preoperative MRI with pelvic phased-array coils followed by radical
      prostatectomy. The MRI findings were correlated with completely embedded serially
      sliced and whole-mounted sections of the prostate gland and clinical staging.
      RESULTS: Overall accuracy of 57.1% was obtained, with specificity of 90.0% and
      sensitivity of 27.3%. All but one case of locally advanced disease missed by MRI
      was microscopic. Clinical staging in these cases also achieved accuracy of 57.1%,
      specificity of 90.0% and sensitivity of 27.3%. CONCLUSIONS: MRI with a phased
      array coil has high specificity but low sensitivity for detection of
      extraprostatic disease. Phased-array MRI does not image microscopic tumour
      extension. It did not perform better than clinical staging and is not recommended
      for routine staging.

PMID- 15564168
TI  - Colostomy with vancomycin administration as an effective treatment for toxic
      megacolon associated with fulminant pseudomembranous colitis: a case report.
AB  - We report a case of toxic megacolon associated with fulminant pseudomembranous
      colitis. A 72-year-old woman was admitted with severe dehydration and shock.
      Computed tomography showed evidence of diffuse thickening of the colonic wall,
      colonic dilatation and ascites. She underwent transverse colostomy and received
      postoperative vancomycin, both orally and by administration from the stoma. Her
      clinical situation improved dramatically following surgery. When a patient is
      unable to tolerate subtotal colectomy and ileostomy because of a severe overall
      condition, temporary colostomy followed by administration of vancomycin through
      the stoma is recommended.

PMID- 15564167
TI  - Randomized comparison of piperacillin/tazobactam versus imipenem/cilastatin in
      the treatment of patients with intra-abdominal infection.
AB  - OBJECTIVES: Treatment of intra-abdominal infections remains a challenge because
      of their polymicrobial nature and associated mortality risk. Broad-spectrum
      empiric coverage is usually required. This randomized study compared the efficacy
      and safety of intravenous piperacillin/tazobactam with those of intravenous
      imipenem/cilastatin in the treatment of 293 hospitalized patients with intra
      abdominal infection. METHODS: A total of 149 patients received
      piperacillin/tazobactam 4 g/500 mg every 8 hours, and 144 patients received
      imipenem/cilastatin 500 mg/500 mg every 6 hours. Efficacy was evaluated by
      clinical and bacteriological response. Safety was evaluated by analysis of
      adverse events and physical and laboratory examinations. RESULTS: Clinical and
      bacteriological responses in both evaluable treatment groups were equivalent. The
      clinical success was 97% (108/111) for piperacillin/tazobactam and 97% (100/103)
      for imipenem/cilastatin. Bacteriological success was 97% (67/69) for
      piperacillin/tazobactam and 95% (61/64) for imipenem/cilastatin. The most common
      pathogens were Escherichia coli, Klebsiella pneumoniae, Enterobacter species and
      Pseudomonas aeruginosa. The frequencies of treatment-related adverse events were
      similar (16 with piperacillin/tazobactam and 19 with imipenem/cilastatin).
      CONCLUSIONS: These results suggest that the safety and efficacy of
      piperacillin/tazobactam administered every 8 hours are equivalent to those of
      imipenem/cilastatin administered every 6 hours for the treatment of intra
      abdominal infections.

PMID- 15564169
TI  - Radiological findings in two patients with cow's milk allergic enterocolitis.
AB  - Cow's milk allergic enterocolitis is a common paediatric gastrointestinal
      disease. However, radiological findings from contrast studies have rarely been
      reported. We report two Japanese neonate patients with cow's milk allergic
      enterocolitis with vomiting, bloody stool and unique findings on upper
      gastrointestinal contrast study. Upper gastrointestinal contrast study showed
      folds of the small intestine to be thickened, such as in spasm, or ribbon-like
      cords in both cases. There was also poor passage from the duodenum to the jejunum
      in one case. In addition, there were spastic findings on lower gastrointestinal
      contrast study in part of the large colon in one case. Clinicians, including
      paediatric surgeons, treating neonates with bloody stool and/or vomiting should
      thus be aware that unique findings on upper and lower gastrointestinal contrast
      studies may be useful in suspecting cases with cow's milk allergic enterocolitis.

PMID- 15564170
TI  - Isolated mediastinal lymphangioma herniating through the intercostal space.
AB  - Lymphangiomas are congenital malformations of the lymphatic system, and 90% have
      manifested by the end of the second year of life. While 75% of these are located
      in the cervical region, only 2% to 3% are associated with an intrathoracic
      extension. An isolated mediastinal lymphangioma without a cervical component is
      an uncommon occurrence. Presented here is an isolated mediastinal lymphangioma
      that herniated through the intercostal space to present as a cystic mass in the
      parasternal region, which has not been reported so far.

PMID- 15564171
TI  - Intrahepatic biliary cystadenoma presenting with obstructive jaundice.
AB  - Biliary cystadenoma (BCA) is a rare neoplasm of the bile duct with malignant
      potential. We report a case of intrahepatic BCA with an unusual presentation of
      obstructive jaundice. Computed tomography scan of the abdomen revealed a dilated
      common bile duct and intrahepatic ducts with internal septa. Endoscopic
      retrograde cholangiography showed an oval filling defect in the bile duct causing
      the obstruction. At laparotomy, this proved to be a multiloculated mucinous polyp
      in the common bile duct, with its origin in the left intrahepatic duct, detected
      using intraoperative choledochoscopy. A left hemihepatectomy was performed, and
      histology confirmed intrahepatic mucinous BCA with mesenchymal stroma. The
      imaging process and surgical options for BCA are discussed.

PMID- 15564172
TI  - Pseudo-Bouveret's syndrome.
AB  - We report a patient with gastric outlet obstruction due to gallstone, with
      clinical and imaging features mimicking Bouveret's syndrome. However, the
      obstruction was simply due to extrinsic compression by a gallstone without
      cholecystoduodenal fistula formation. Laparoscopic cholecystectomy cured the
      patient.

PMID- 15564174
TI  - Sentinel lymph node biopsy -- here to stay.

PMID- 15564173
TI  - Deep vein thrombosis and malignancy: a surgical oncologist's perspective.
AB  - Oncology patients are at increased risk of developing deep vein thrombosis (DVT)
      and its potentially fatal sequel, pulmonary embolism. This is due to multiple
      factors, including the presence of the malignancy itself, comorbid factors and
      therapy-related interventions. Issues that are peculiar to venous thrombosis in
      the oncology setting are discussed, based on a MEDLINE search of the English
      literature. These include the need to screen for malignancy in idiopathic DVT, a
      high index of suspicion for venous thrombosis in the cancer patient, the use of
      vena cava filters, and the anti-neoplastic effects of heparin. Asian patients
      appear to have a lower incidence of DVT compared to Caucasians. A recommended
      regimen for prophylaxis of DVT must take into account the varying thrombosis risk
      associated with different malignancies. Cancer patients not undergoing abdominal,
      pelvic or orthopaedic surgery (e.g. mastectomy) should use elastic compression
      stockings and be mobilized early, whereas low-molecular-weight heparin should be
      given to those undergoing more major surgery. In advanced malignancy, treatment
      of DVT palliates symptoms. These patients may need long-term anticoagulation with
      warfarin.

PMID- 15564175
TI  - Pathological evaluation of sentinel lymph nodes for breast cancer.
AB  - Recently, sentinel lymph node (SLN) biopsy has been employed to avoid unnecessary
      lymph node dissection, because SLN negativity for carcinoma metastases may imply
      an extremely low possibility of non-SLN involvement. Pathological evaluation is
      essential, but standardized procedures have not yet been determined.
      Intraoperative consultation, either by frozen section (multiple slices are
      desirable) or touch imprint cytology, are usually very useful. Their accuracy,
      however, is variable and depends on the procedures used, but specificity is
      characteristically 100%, and the missed metastatic focus is always quite minute.
      After fixation, multiple sections, immunohistochemistry, and their combination
      will be able to detect small metastatic foci more frequently. The clinical
      significance of small or submicro- or occult metastases have not yet been
      clarified, and further investigations are needed. If the SLN is positive for
      carcinoma metastases, both the procedure for detection and the size of the
      metastatic focus should be clarified on the pathological reports.

PMID- 15564176
TI  - Sentinel lymph node biopsy following neoadjuvant chemotherapy: review of the
      literature and recommendations for use in patient management.
AB  - Breast cancer is a significant health problem worldwide and is one of the leading
      causes of cancer-related mortality in women. Preoperative chemotherapy has become
      the standard of care for patients with locally advanced disease and is being used
      more frequently in patients with early-stage breast cancer. Sentinel lymph node
      biopsy has shown great promise in the surgical management of breast cancer
      patients, but its use following preoperative chemotherapy is yet to be
      determined. Eleven studies have been published with respect to the accuracy of
      sentinel lymph node biopsy following neoadjuvant chemotherapy. Ten studies showed
      favourable results, with the ability to identify a sentinel lymph node in 84% to
      98% of cases, and reported false negative rates ranging from 0% to 20%. The
      accuracy of sentinel lymph node biopsy following preoperative chemotherapy for
      breast cancer ranges from 88% to 100%, with higher rates when specific techniques
      and inclusion criteria are applied. The published literature supports the use of
      sentinel lymph node biopsy for assessment of the axilla in patients with
      clinically node-negative disease following preoperative chemotherapy.

PMID- 15564177
TI  - Selective sentinel lymphadenectomy for breast cancer in the United States.
AB  - Lymph node status is the most reliable prognostic indicator for breast cancer
      patients. Sentinel lymph nodes (SLNs) are the first draining lymph nodes for
      metastatic breast cancer to spread from the primary site. Although the
      therapeutic role of selective sentinel lymphadenectomy (SSL) in breast cancer has
      not been determined, the practical significance is that it is being used as a
      staging procedure, so that a negative SLN can spare a patient more extensive
      axillary lymph node dissection (ALND) with its associated morbidity. If the SLN
      is negative, the negative predictive value of the remaining nodal basin for
      breast cancer exceeds 95%. SSL selects out one or a few SLNs and permits more
      extensive study of the nodes by the pathologist. Such extensive examination would
      not be practical for the many nodes yielded by a standard ALND. SSL is rapidly
      evolving into a standard approach for staging primary breast cancer in the United
      States, without the maturation of results from clinical trials.

PMID- 15564178
TI  - Recent development of sentinel lymph node biopsy for breast cancer in Japan.
AB  - The number of breast cancer cases undergoing sentinel lymph node biopsy (SLNB)
      has been increasing with the number of articles published in Japan. SLNB using
      the dye method alone is performed in about one-third of patients. Analysis of
      questionnaire responses from 40 institutions in Japan revealed an identification
      rate by the dye method alone of 87%, compared with 96% using the combined method;
      the combined method is now recognized in Japan as superior to the dye method
      alone. No dyes have been specifically approved by the government for use in SLNB,
      and physicians have been using several inappropriate dyes as tracers for SLNB,
      such as indocyanine green, patent blue, indigo carmine, and isosulfan blue. The
      colloidal radiotracers used in Japan include tin colloid, stannous phytate,
      rhenium sulfate and human serum albumin. Albumin colloid and sulfur colloid are
      not commercially available in Japan. Small-size tin colloids, stannous phytate
      and rhenium sulfate all yield good results in terms of detection and false
      negative rates. Provided that the surgeon has adequate experience in SLNB, a
      negative sentinel node can serve as a substitute for negative results from
      axillary lymph node dissection. Although many institutions have introduced SLNB,
      few reports have focused on the results of SLNB without axillary dissection
      because of short follow-up times and small number of patients. The final decision
      as to whether SLNB is an adequate substitute for axillary dissection awaits the
      results of prospective randomized trials.

PMID- 15564179
TI  - Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which
      might be an alternative to axillary lymph node dissection in breast cancer
      patients?
AB  - Axillary lymph node status has limited prognostic significance in breast cancer
      patients and much improvement can be made. Sentinel lymph node biopsy is emerging
      as an alternative to axillary lymph node dissection for staging, but its
      prognostic relevance is still uncertain. Detection of micrometastases in sentinel
      nodes and bone marrow may provide more information, but the clinical significance
      still needs to be confirmed by ongoing large trials. In this review, we focus on
      the possibility of sentinel lymph node biopsy or detection of bone marrow
      micrometastasis replacing traditional axillary lymph node dissection.

PMID- 15564180
TI  - Australasian experience and trials in sentinel lymph node biopsy: the RACS SNAC
      trial.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) has been rapidly adopted by surgical
      oncologists in the management of invasive breast cancer. This study reviews the
      Royal Australasian College of Surgeons (RACS) Sentinel Node versus Axillary
      Clearance (SNAC) trial and reports an interim analysis of the first 150 subjects.
      Other currently open multi-institutional randomized trials in SLNB are reviewed.
      METHODS: The SNAC trial is a multicentre, centrally randomized, phase III
      clinical trial. Subjects are randomized to SLNB alone (with completion axillary
      clearance, AC, for sentinel node-positive patients) or AC plus SLNB, with
      stratification according to age (< 50 years, more than or equal to 50 years),
      primary tumour palpability (palpable vs impalpable), lymphatic mapping technique
      (blue dye plus scintigraphy vs blue dye alone) and centre. RESULTS: The trial was
      launched in May 2001 in two centres. Randomization continues currently at the
      rate of approximately 30 subjects per month (total, 1,012 at the time of writing)
      from 32 participating centres in Australia and New Zealand. Data from the first
      150 subjects have been analysed to assess: compliance with randomized treatment
      allocation; measures of test performance for SLNB (detection, removal,
      sensitivity, specificity and false-negative rates); measures of arm volume,
      function, symptoms and quality of life; and sample size estimates. CONCLUSIONS:
      The SNAC trial is one of the fastest accruing clinical trials in Australasia. It
      is on track to determine whether differences in morbidity, with equivalent cancer
      related outcomes, exist between SLNB and AC for women with early breast cancer.

PMID- 15564181
TI  - Current European studies of sentinel lymph node biopsy for breast cancer.
AB  - The paradigm shift in the assessment of the axilla in breast surgery has evoked
      specific clinical issues. In a population where breast cancer is diagnosed early
      and service screening mammography is applied, the chance for a woman to be free
      of lymph node metastases is approximately 60%. Currently, there are three ongoing
      and one published randomized series on sentinel node lymphadenectomy in Europe,
      comprising more than 100 patients. These studies address the important issues of
      morbidity, quality of life and long-term outcome measures such as survival and
      recurrence.

PMID- 15564182
TI  - Sentinel lymph node biopsy assessment using intraoperative imprint cytology in
      breast cancer patients: results of a validation study.
AB  - OBJECTIVE: Sentinel lymph node biopsy (SLNB) in breast cancer patients is
      emerging as a promising minimally-invasive tool. There has been an exponential
      increase in the literature related to sentinel lymph nodes (SLN) in breast cancer
      patients, mainly from Western centres. This study was carried out to address
      issues relevant to breast cancer patients in developing countries, including the
      method of SLN detection, the role of imprint cytology in the assessment of SLN,
      and the role of SLNB in locally advanced breast cancer (LABC). METHODS: This
      study included 76 women with breast cancer. The blue-dye method was used to
      identify the sentinel node. Touch imprint smears were prepared from the sectioned
      node, stained using the Jenner-Geimsa technique, and examined for tumour
      deposits. RESULTS: Sentinel nodes were identified in 69 of 76 patients. The
      sensitivity, specificity and accuracy of SLNB in predicting axillary node status
      were 84.2%, 100% and 91.3%, respectively. The sensitivity, specificity and
      accuracy of intraoperative imprint cytology were 96.9%, 100% and 98.6%,
      respectively. CONCLUSIONS: These results prove that high levels of SLN detection
      can be achieved using the blue-dye method alone. Its role in LABC patients needs
      further evaluation. In view of promising results, imprint cytology should be used
      more frequently as an alternative to frozen section for the assessment of
      sentinel nodes.

PMID- 15564183
TI  - Flat colorectal lesions: colonoscopic detection without dye spray or
      magnification and clinical significance.
AB  - OBJECTIVE: The detection of flat colorectal lesions with possible malignant
      potential has been described by Japanese endoscopists. This study looks at the
      detection of flat lesions using standard colonoscopic techniques and examines the
      clinical significance of these lesions. METHODS: The records of patients who
      underwent complete colonoscopy by a single colorectal surgeon in an outpatient
      setting over a 4-year period were reviewed. The site and number of flat lesions
      and their histology were noted. Patients with incomplete intubation of the colon
      were excluded. RESULTS: A total of 491 patients underwent 593 colonoscopic
      examinations. There were 236 flat lesions identified in 91 patients: 24% (56/236)
      were adenomas showing mild or moderate dysplasia, and 63% (148/236) were
      hyperplastic. CONCLUSIONS: Flat colorectal lesions are common and can be detected
      without the aid of dye spray and magnification. One-quarter of these lesions are
      adenomatous and we recommend routine hot biopsy or polypectomy of these lesions.

PMID- 15564184
TI  - Plasma D-lactic acid level: a useful marker to distinguish perforated from acute
      simple appendicitis.
AB  - Early diagnosis of perforated appendicitis is important for reducing morbidity
      rates. The aim of this study was to determine the value and utility of plasma D
      lactic acid levels in identifying the type of appendicitis. In this clinical
      study, plasma D-lactic acid levels were assessed in 44 consecutive paediatric
      patients (23 with acute appendicitis, 21 with perforated appendicitis) before
      laparotomy. D-lactic acid levels were determined by an enzymatic
      spectrophotometric technique using a D-lactic acid dehydrogenase kit. Patients
      with perforated appendicitis had higher D-lactic acid levels (3.970 +/- 0.687
      mg/dL) than patients in the control group (0.478 +/- 0.149 mg/dL) and patients
      with acute appendicitis (1.409 +/- 0.324 mg/dL; p < 0.05). For a plasma D-lactic
      acid level greater than 2.5 mg/dL, the sensitivity and specificity of the D
      lactic acid assay were 96% and 87%, respectively. The positive predictive value
      was 87%, the negative predictive value was 96%, and the diagnostic value was 91%.
      These results suggest that the measurement of plasma D-lactic acid levels may be
      a useful adjunct to clinical and radiological findings in distinguishing
      perforated from acute non-perforated appendicitis in children.

PMID- 15564185
TI  - Inguinal hernia repair by surgical trainees at a Malaysian teaching hospital.
AB  - OBJECTIVE: To assess the outcome of inguinal hernia repaired by surgical trainees
      at Universiti Kebangsaan Malaysia Hospital. METHODS: Retrospective review of 103
      patients who underwent surgery between November 2001 and October 2002. RESULTS:
      The mean age of patients was 50 years and the male-to-female ratio was 20:1. Most
      hernias (60%) were right-sided inguinal hernias. Admissions consisted of 60%
      elective, 31% day-case and 9% emergency. General anaesthesia was administered in
      66% of cases, spinal anaesthesia in 33% and local anaesthesia in 1%. Ten inguinal
      hernia repairs were performed by first-year trainees, 61 by third-year trainees
      and 19 by fourth-year trainees. First-year trainees did more darning (60%) and
      fewer mesh (40%) repairs. Third-year trainees still used darning (57%) but also
      performed more mesh repairs (43%). Fourth-year trainees performed 68% darning
      (mainly to teach the first-year trainees) and 32% mesh repairs. Senior surgeons
      assisted in 13 difficult cases where mesh repair was preferred (92%) to darning
      repairs (8%). Prophylactic antibiotic was more frequently used in patients
      undergoing mesh repair (p < 0.001). The mean operative time was the same for both
      types of repair. There were no significant differences in complications between
      the two types of repair. One hernia recurred after darning repair but none after
      mesh repair. CONCLUSIONS: Mesh repair of inguinal hernia is effective. Trainees
      easily acquire this skill and it becomes their preferred method of repair.

PMID- 15564186
TI  - Outpatient laparoscopic cholecystectomy in Hong Kong Chinese -- an outcome
      analysis.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) is now the procedure of choice for
      symptomatic gallbladder disease. Although many recent studies, mostly from
      abroad, report that it can be performed safely in the outpatient setting, the
      experience of outpatient LC in Hong Kong is still limited. This retrospective
      study evaluated the feasibility, safety and patient acceptance of outpatient LC
      in Hong Kong Chinese patients. PATIENTS AND METHODS: The data of 73 consecutive
      patients who had undergone outpatient LC between February 2000 and October 2002
      in the Day Surgery Centre of Tung Wah Hospital were prospectively collected and
      reviewed. The selection criteria for patients undergoing outpatient LC included
      American Society of Anesthesiologists risk classification I or II, age less than
      70 years, and the availability of a competent adult to accompany the patient home
      and look after them for 24 hours. No effort was made to exclude complicated
      cases. After assessment by the operating surgeon, patients were discharged from
      the Day Surgery Centre in the afternoon when their clinical condition satisfied
      pre-defined discharge criteria. All patients were followed up in the Day Surgery
      Centre in the first and fourth postoperative weeks. RESULTS: The same-day
      discharge rate was 88% and the conversion rate was 4%. Six patients (8.2%) with
      uneventful LC required hospitalization after the procedure. There was no major
      complication and no unplanned admission. Two patients had port site wound
      infection requiring hospital admission at the first follow-up. Patient
      satisfaction was high, pain acceptance was good, and analgesic consumption was
      minimal. Mild fat intolerance was common in patients postoperatively (> 50%), but
      this had almost all resolved by postoperative week four. All patients were able
      to resume their usual daily activities within 2 weeks after surgery. CONCLUSIONS:
      LC is a safe and feasible outpatient procedure in Hong Kong, with high levels of
      patient satisfaction. A prospective study with a larger patient population is
      warranted to verify whether it should be recommended as treatment for gallstone
      disease in selected patients in future.

PMID- 15564187
TI  - Noninvasive assessment of patency of internal ureteral stent: role of colour
      Doppler ultrasound.
AB  - OBJECTIVE: To compare colour Doppler ultrasonography (CDU) and retrograde
      cystography in the assessment of the patency of internal ureteral stents.
      PATIENTS AND METHODS: Thirty-two patients with 33 internal ureteral stents were
      evaluated for patency of the internal ureteral stent using both CDU and
      retrograde cystography. Real-time ultrasonography and CDU were performed before
      retrograde cystography. Stent patency was defined as seeing flow from the distal
      end of the stent in the urinary bladder or iodinated contrast in the renal
      pelvis. The two investigators had no prior knowledge of the other's results.
      After completion of both investigations, stent patency was proved by direct
      inspection of the stent after removal. RESULTS: Both investigations showed the
      same result in 27 of the 33 stents. Stent patency was found if either
      investigation was positive. The accuracies of retrograde cystography, CDU and
      both were 73%, 79% and 85%, respectively. CONCLUSIONS: CDU is a noninvasive
      method with high accuracy. Detection of flow at the distal end of the stent is
      helpful, but absence of flow may or may not indicate an obstructed stent and
      further investigation should be performed.

PMID- 15564188
TI  - Early experience with robot-assisted laparoscopic radical prostatectomy.
AB  - INTRODUCTION: We assessed the feasibility of a robot-assisted laparoscopic
      radical prostatectomy (rLRP) programme through a review of our early experience.
      PATIENTS AND METHODS: Seventeen patients underwent rLRP between 1 February 2003
      and 31 December 2003 at Singapore General Hospital. All patients had
      histologically confirmed adenocarcinoma on prostate biopsy and a negative bone
      scan. The Da Vinci robot was employed. The Montsouris technique was used for our
      first eight patients, and the Vattikuti Institute Prostatectomy technique was
      used for all subsequent patients. We studied perioperative parameters and early
      surgical outcome prospectively. RESULTS: The mean age at diagnosis was 63.9 +/-
      5.6 years. The median Gleason sum was 6 (range, 5-9), and mean pretreatment
      prostate-specific antigen level was 10.5 +/- 5.4 ng/mL. The mean set-up time was
      34 +/- 18 minutes, and mean dissection time was 247 +/- 43 minutes. Perioperative
      blood loss averaged 494 +/- 330 mL, and three patients required blood
      transfusion. Normal diet was resumed after 1.7 +/- 0.6 days. The mean duration of
      bladder catheterization was 9.8 +/- 6.1 days, and mean hospital stay was 2.7 +/-
      1.3 days. There was no perioperative mortality or major complications, and no
      conversion to open radical prostatectomy. From Case 9 onwards, there was
      significant reduction in operating time (284 vs 215 minutes), blood loss (650 vs
      400 mL) and hospital stay (3.8 vs 1.8 days). CONCLUSIONS: rLRP is feasible in a
      practice with a low volume of radical prostatectomies. Significant improvement in
      perioperative parameters occurs after the first eight cases. This technique
      confers the benefits of enhanced precision and dexterity for complex laparoscopic
      work in the pelvic cavity.

PMID- 15564189
TI  - Meta-analysis of randomized controlled trials on hydrocolloid occlusive dressing
      versus conventional gauze dressing in the healing of chronic wounds.
AB  - Chronic wound management is a difficult area in surgical practice. A wide range
      of dressings have been recommended for the management of chronic wounds. The
      present meta-analysis was undertaken to determine the effectiveness of
      hydrocolloid dressing (HCD) in the healing of chronic wounds compared with
      conventional gauze dressing. All available controlled clinical trials published
      before December 2001 that compared HCD to conventional gauze dressing in the
      healing of chronic wounds were systematically reviewed. We identified and
      analysed 12 randomized trials (11 published; 1 unpublished) comprising 693
      patients with 819 ulcers. The overall odds ratio under the fixed effect model was
      1.72, that is, 72% more ulcers healed completely with HCD than with conventional
      gauze dressing. This result was both clinically and statistically significant.

PMID- 15564190
TI  - Benign retroperitoneal cyst of Mullerian type.
AB  - Retroperitoneal cysts are rare, usually asymptomatic, lesions. We present the
      case of a 42-year-old woman with an asymptomatic abdominal mass. The mass excised
      at our district hospital was found in the retroperitoneum. Histologically, the
      cyst was lined with benign Mullerian-type epithelium. The classification,
      aetiology and clinical manifestations of retroperitoneal cysts are discussed.
      Retroperitoneal cysts present as an acute abdomen in only a minority of cases.
      Ultrasound is the most reliable test for their detection, usually followed by
      computed tomography and/or an upper gastrointestinal series. Optimally, these
      cysts should be completely excised.

PMID- 15564191
TI  - Three-layer technique to close a persistent tracheo-oesophageal fistula.
AB  - This report of a patient with a persistent tracheo-oesophageal (TE) fistula after
      removal of a speech valve describes a modification of the technique described by
      Rosen et al for closing TE. Under local anaesthesia, an incision was made above
      the stoma edge from 9 o'clock to 3 o'clock. The trachea was separated from the
      oesophagus to beyond the fistula, and the fistula tract was excised. The
      oesophageal opening was closed in layers and a local flap rotated from the
      adjacent sternocleidomastoid muscle and sutured over the oesophageal closure. The
      trachea was then closed separately.

PMID- 15564192
TI  - Stromal sarcoma of the breast: a case report.
AB  - We report a case of a 36-year-old lady who presented with a huge fungating tumour
      that involved the entire right breast. The tumour was diagnosed histologically as
      undifferentiated primary stromal tumour of the breast with axillary lymph node
      metastasis. We review the literature of this rare malignant tumour. Stromal
      sarcomas of the breast lack epithelial participation, and diagnosis of these
      tumours can be difficult. Genome-wide expression profiling is currently used to
      determine the cell of origin of most sarcomas. Surgery offers the best
      therapeutic option. Adjuvant radiotherapy is not very beneficial, while
      chemotherapy has, to date, no established role in the management of this disease.
      The prognosis is dismal for patients with lymph node involvement. The size of the
      tumour has a lesser bearing on outcome.

PMID- 15564193
TI  - Common bile duct perforation due to tuberculosis: a case report.
AB  - A young man with HIV presented with biliary peritonitis secondary to spontaneous
      common bile duct perforation. Investigation revealed that the perforation was due
      to Mycobacterium tuberculosis. Tuberculosis of the bile duct is uncommon and
      usually presents with obstructive jaundice due to stricture. Bile duct
      perforation due to tuberculosis is extremely rare. Its management is discussed.

PMID- 15564194
TI  - Hepatic actinomycosis presenting as a liver tumour: case report and literature
      review.
AB  - Hepatic actinomycosis poses a difficult problem in both diagnosis and management.
      We report the management of a patient with isolated hepatic actinomycosis, and
      review the clinical features and management of patients with hepatic
      actinomycosis mimicking liver tumour.

PMID- 15564195
TI  - Intestinal obstruction due to phytobezoars of banana seeds: a case report.
AB  - Phytobezoars are a well-known, though rare, cause of mechanical alimentary tract
      obstruction. They occur mainly in patients who have undergone abdominal surgery,
      where most literature reports describe the causes as persimmons and oranges. We
      report four cases, seen within a period of 19 months in Laos, with intestinal
      obstruction caused by phytobezoars from jungle banana seeds. They had no history
      of previous gastrointestinal surgery. The recommended therapy in total
      obstruction is laparotomy, "milking" through the ileocaecal junction, or
      enterotomy and direct extraction. As recurrence and presentation at multiple
      sites are possible, all of the gastrointestinal tract should be thoroughly
      examined intraoperatively.

PMID- 15564196
TI  - Building professionalism and communication through active small-group sessions.

PMID- 15564197
TI  - Alopecia areata: autoimmune basis of hair loss.
AB  - Alopecia areata (AA) is a heterogeneous disease characterized by nonscarring hair
      loss on the scalp or any hair-bearing surface. A wide range of clinical
      presentations can occur -- from a single patch of hair loss to complete loss of
      hair on the scalp (alopecia totalis) or the entire body (alopecia universalis).
      Particularly in severe or chronic cases, AA may cause considerable psychological
      and emotional distress for affected individuals. The estimated lifetime risk of
      developing AA is 1.7%. While the precise etiology of this common disorder has not
      been elucidated, a substantial body of evidence suggests that AA is an organ
      specific, autoimmune disease, targeted to hair follicles. However, the antigenic
      target(s), mechanisms, and consequences of autoimmune attack in AA have yet to be
      determined. Here, we critically explore the evidence supporting the hypothesis
      that AA is an autoimmune disease and propose specific pathways by which self
      directed immune responses are generated.

PMID- 15564198
TI  - Crossing the Rubicon. Preparing residents for professional life after residency.
AB  - In addition to clinical skill and knowledge of basic science, graduating
      residents need decision-making and communication skills, and an understanding of
      the cultural and prejudicial divides that sometimes create conflicts and
      misunderstandings in the clinical arena. This paper summarizes a program that one
      institution has adopted, which attempts to introduce topics in the humanities
      into the conventional curriculum. The goal is to enable graduating residents to
      think and to express their views more creatively and assertively, and to give
      them a greater understanding of some of the individual and cultural attitudes
      they are certain to encounter in practice.

PMID- 15564199
TI  - Identification of the keratin K9 R162W mutation in patients of Italian origin
      with epidermolytic palmoplantar keratoderma.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant skin
      disorder characterized by hyperkeratosis of the palms and soles associated with
      histologic findings of hyperkeratosis and epidermolysis. Ultrastructurally, there
      is vacuolization of the cytoplasm and abnormal keratin filament network with
      tonofilament clumping. EPPK is caused by mutations in the keratin 9 gene (KRT9),
      which is expressed exclusively in suprabasal keratinocytes of palmoplantar
      epidermis. The mutation R162W is the most frequent keratin 9 alteration reported
      in patients from different geographical areas. We present three unrelated Italian
      families affected by EPPK in which we confirmed the presence of the R162W
      mutation, by RT-PCR analysis followed by sequencing of the KRT9 gene, in all
      affected members. The finding of the same mutation in all patients, together with
      the previous reports of the disease, strongly suggest that position 162 of the
      KRT9 gene represents a mutation "hot-spot", probably due to the peculiarity of
      the sequence.

PMID- 15564200
TI  - Genetic analyses of two cases of Werner's syndrome.
AB  - We report two cases of Werner's syndrome (WS). First, a 42-year-old Japanese man
      was referred on suspicion of systemic sclerosis (SSc) because of scleroderma-like
      skin atrophy and foot ulcers. Second, a 51-year-old woman with malignant fibrous
      histiocytoma was referred on suspicion of premature aging syndrome. Because both
      patients had many typical manifestations compatible with WS, we made a clinical
      diagnosis of WS. Genetic analyses revealed a homozygous mutation, an A deletion
      at nucleotide 3677 of WS gene (WRN) in the first case and a homozygous mutation,
      a G to C substitution at one base upstream of exon 26 of WRN in the second case.
      Both mutations were consistent with those previously reported in Japanese WS
      patients.

PMID- 15564201
TI  - Basal cell carcinoma with ductal and glandular differentiation: a
      clinicopathological and immunohistochemical study of 10 cases.
AB  - The object of this study was to elucidate the clinicopathological and
      immunohistochemical features of BCC with tubular structures. From the examination
      of 600 BCC specimens, we selected 10 cases of BCC with tubular structures.
      Immunohistochemistry was performed in these ten cases using antibodies against
      cytokeratins. All 10 BCCs (3 men and 7 women) were located on the face and scalp,
      particularly on the eyelid. The tubular structures could be classified
      histopathologically into ductal structures and glandular structures, which was
      supported by the results of the immunohistochemical study. The ductal structures
      represented various types and forms, small to medium-sized (the most common
      form), tiny, dilated, well-differentiated or acrosyringeal types. The glandular
      structures in one case suggested the features of apocrine secretion. BCC with
      tubular structures affected women more than men, and the favored location was the
      eyelid. The tubular structures in these BCCs differentiated toward either ductal
      or glandular structures, presumably of apocrine nature.

PMID- 15564202
TI  - The ultrastructural characteristics of the hair bulb of segmented heterochromia
      in the scalp hair.
AB  - Segmented heterochromia is a pigmentary disorder characterized by alternating
      dark and light segments on each hair shaft. Our aim was to observe the
      ultrastructure of hair shafts and bulbs to understand the pathogenesis of the
      disease. Biopsy specimens including normal or diseased hair follicles were
      prepared for transmission electron microscopy. In dark segments, dense and
      ellipsoidal melanosomes were noted while small, round ones were found in the
      light segments. Two groups of melanosomes lined up on the matrix, one of which
      was composed of compact ellipsoidal melanosomes, and the other was composed of
      melanosomes with irregular sizes and shapes. Melanocytes seemed to be under
      necrosis, apoptosis, or dark cell transformation. Langerhans cells were found in
      the bulb. Two kinds of melanosomes were produced in the same hair bulb
      simultaneously. Degenerating melanocytes might produce deformed melanosomes.
      Langerhans cells might be involved in the death of melanocytes. It is unknown how
      either group of melanosomes is adopted and transferred to the hair cortex
      producing the characteristic pattern of pigmentation.

PMID- 15564203
TI  - European recommendations on the use of oral antibiotics for acne.
AB  - Non-rational prescribing of oral antibiotics in acne is common, and there is
      currently an unmet need for up-to-date guidelines that specifically address these
      issues. Presented here is a set of recommendations on the use of oral antibiotics
      in acne, developed by a group of European acne specialists, designed to be
      considered by dermatologists and general practitioners in their daily practice
      throughout Europe. Recommendations cover optimal choice of antibiotic, drug
      doses, duration of treatment, combination treatment, and maintenance therapy.

PMID- 15564204
TI  - Clinical usefulness of oral itraconazole, an antimycotic drug, for refractory
      atopic dermatitis.
AB  - We investigated the clinical usefulness of oral itraconazole for refractory
      atopic dermatitis in a crossover study. Patients with refractory atopic
      dermatitis were divided into two groups: Group A; a combination of itraconazole
      plus a conventional lactobacillus preparation was administered for 8 weeks,
      followed by lactobacillus preparation alone for 8 weeks, Group B; lactobacillus
      preparation alone was administered for 8 weeks, followed by itraconazole plus
      lactobacillus for 8 weeks. In both groups, a decrease in dose or strength of
      concomitant topical steroids was observed at the end of the treatment course of
      itraconazole, and improvement of parameters such as eosinophil count, serum IgE
      level and specific IgE antibody titers to fungi was also observed after the
      administration of itraconazole. These results suggest that oral itraconazole is
      useful for the treatment of intractable atopic dermatitis patients who do not
      respond to conventional therapeutic approaches.

PMID- 15564205
TI  - Mucocutaneous telangiectases of the head and neck in individuals with hereditary
      hemorrhagic telangiectasia -- analysis of distribution and symptoms.
AB  - Telangiectases are a diagnostic clue of hereditary hemorrhagic telangiectasia
      (HHT, Rendu-Osler-Weber disease), but they are not specific to HHT. The
      characteristic features of telangiectases were studied in a group of 70
      individuals with this disorder. The files, including photo and video
      documentation of these patients, were reviewed with regard to mucocutaneous
      vascular lesions. Telangiectases could be identified within the nasal mucosa in
      90% of the HHT patients. Extranasal telangiectases were identified in descending
      order in the oral cavity, the facial skin, the hands, the auricles and the
      thorax. The vascular lesions showed considerable variation in size and shape, and
      on the nasal mucosa they were most commonly hemorrhagic. The earliest onset of
      cutaneous telangiectases was documented at the age of 6 years. Contrary to
      previous communications, more than 25% of patients had hemorrhages outside the
      nose. These hemorrhages were self-limiting in most cases. Prolonged hemorrhages
      requiring treatment were observed in 12% of cases. Such severe hemorrhages
      originated from telangiectases of the base of the tongue, the body of the tongue,
      the fingers and the skin of the supraclavicular fossa. We conclude that
      telangiectases occur at an earlier age than generally thought and are a hallmark
      of a serious disorder rather than a cosmetic problem.

PMID- 15564206
TI  - Localised vulva Langerhans cell histiocytosis.
AB  - A cutaneous lesion as sole manifestation of adult Langerhans cell histiocytosis
      is rare. We report a 65-year old female who presented with vulvar ulcers.
      Histological examination of the ulcer showed diffuse proliferation of histiocytic
      cells with large bright cytoplasm that were positively stained for anti-S-100
      protein and anti-CD1a antibodies by immunohistochemistry. Electron microscopy
      demonstrated Birbeck granules in the cytoplasm of the cells. Since there was no
      other organ involvement, the patient was treated by complete surgical excision
      without recurrence or other-organ involvement in the 1-year follow-up period.

PMID- 15564207
TI  - Generalized pustular psoriasis (von Zumbusch) following iatrogenic
      hypocortisolism.
AB  - Generalized pustular psoriasis can be triggered by hypocalcemia, pregnancy,
      stress and drugs but frequently has no obvious cause. We report a case which was
      only cured after treatment of iatrogenic adrenal axis suppression. A 41 year old
      woman had been suffering for nine months from a generalized pustular psoriasis
      which had occurred after a three week topical corticosteroid therapy of plaque
      psoriasis with 90 g of betamethasone dipropionate + 2% salicylic acid. Successive
      systemic treatments failed but topical corticosteroids brought relief to the
      patient. Cortisol level was found to be very low. Further investigations showed
      iatrogenic adrenal axis suppression. Hydrocortisone supplementation brought
      spectacular improvement and complete healing in a few months.We suggest that our
      patient was extremely sensitive to corticosteroids because the first pustules
      appeared after a conventional topical treatment. Adrenal axis suppression has
      never been involved in the aggravation of inflammatory dermatoses except in two
      cases of severe atopic dermatitis. Endogen corticosteroids inhibit
      proinflammatory cytokines by a feed-back mechanism and might have a great
      importance in the immune regulation loop. Cortisol level measurement should be
      considered in corticodependent inflammatory dermatoses.

PMID- 15564208
TI  - Multiple cutaneous rhabdomyomas in a child.
AB  - We recently encountered a 4 year-old male patient with congenital, multiple,
      corporeal, cutaneous rhabdomyomas. Pathological examination of the excised tumors
      showed lobular structures in the dermis. The tumor cells contained spherical and
      polygonal eosinophilic cytoplasm with peripherally dislocated nuclei, and were
      positive for myogloblin staining. Extra-cardiac rhabdomyoma is an extremely rare
      condition, and our case might be considered the first of its kind in Japan.

PMID- 15564209
TI  - Relapsing herpes simplex-2 folliculitis in the beard area.
AB  - We describe the case of a 52-year-old immunocompetent man with recurrent
      folliculitis on the left cheek, associated with intense pain. Bacteriological,
      mycological and Tzanck tests from the lesions were negative. Histopathological
      study showed an aspecific flogosis pattern. Virological tests carried out on
      swabs and paraffin-embedded tissue sections from the facial lesions by nested PCR
      technique (nPCR) demonstrated the presence of herpes simplex virus type 2 (HSV?2)
      in both samples. Skin swabs from other healthy areas of the face resulted
      negative for herpetic infection. A diagnosis of recurrent herpetic folliculitis
      by HSV?2 was made. This case report underlines that even in immunocompetent
      patients HSV?2 lesions can feature atypical clinical aspects. In dermatological
      assessment the benefits of routine PCR techniques for differential diagnosis of
      herpetic infection should be considered above all for the prompt initiation of
      antiviral therapy and appropriate patient management.

PMID- 15564210
TI  - Spontaneous regression of multiple tumoral calcinosis in a child.
AB  - We report a case of multiple tumoral calcinosis on the head and back of a one
      year-old boy who had no renal diseases. After an excisional biopsy of one of the
      tumors from the occipital region, all of the tumors spontaneously regressed
      without any further surgical or medical treatment. Although he had neonatal
      hepatitis, his liver function improved as well as the course of the spontaneous
      regression of the tumoral calcinosis. There has been only one case of a child
      with this condition in the literature.

PMID- 15564211
TI  - The tobacco industry in Asia: revelations in the corporate documents.

PMID- 15564212
TI  - Complicity in contraband: British American Tobacco and cigarette smuggling in
      Asia.
AB  - OBJECTIVES: To examine the complicity of British American Tobacco (BAT) in
      cigarette smuggling in Asia, and to assess the centrality of illicit trade to
      regional corporate strategy. METHODS: Analysis of previously confidential
      documents from BAT's Guildford depository. An iterative strategy combined
      searches based on geography, organisational structure, and key personnel, while
      corporate euphemisms for contraband were identified by triangulation. RESULTS:
      BAT documents demonstrate the strategic importance of smuggling across global,
      regional, national, and local levels. Particularly important in Asia, contraband
      enabled access to closed markets, created pressure for market opening, and was
      highly profitable. Documents demonstrate BAT's detailed oversight of illicit
      trade, seeking to reconcile the conflicting demands of control and deniability.
      CONCLUSIONS: BAT documents demonstrate that smuggling has been driven by
      corporate objectives, indicate national measures by which the problem can be
      addressed, and highlight the importance of a coordinated global response via
      WHO's Framework Convention on Tobacco Control.

PMID- 15564213
TI  - "Almost a role model of what we would like to do everywhere": British American
      Tobacco in Cambodia.
AB  - OBJECTIVES: To examine British American Tobacco's (BAT's) renewed interest in
      Cambodia from the early 1990s, reviewing negotiations to establish a joint
      venture and the subsequent conduct of BAT Cambodia (BATC). METHODS: Analysis of
      previously confidential BAT documents relevant to the Cambodian market. RESULTS:
      With the advent of comparative political stability in the early 1990s, BAT was
      quick to explore the possibilities for investment. The Cambodian government
      urgently required foreign investment, offering inducements and assistance to
      investors. In developing a joint venture, BAT saw a cost effective opportunity to
      dominate the local market and to defend its regional interests, Cambodia being
      viewed as strategically located to support smuggling. Given minimal advertising
      regulation, BATC have undertaken wide ranging promotions and sought to prevent
      advances in tobacco control. CONCLUSIONS: BATC is presented as a contribution to
      Cambodia's regeneration, but the documents highlight its exploitation of state
      incapacity and an escalating threat to public health.

PMID- 15564214
TI  - ARTIST (Asian regional tobacco industry scientist team): Philip Morris' attempt
      to exert a scientific and regulatory agenda on Asia.
AB  - OBJECTIVE: To describe how the transnational tobacco industry has collaborated
      with local Asian tobacco monopolies and companies to promote a scientific and
      regulatory agenda. METHODS: Analysis of previously secret tobacco industry
      documents. RESULTS: Transnational tobacco companies began aggressively entering
      the Asia market in the 1980s, and the current tobacco industry in Asia is a mix
      of transnational and local monopolies or private companies. Tobacco industry
      documents demonstrate that, in 1996, Philip Morris led an organisation of
      scientific representatives from different tobacco companies called the Asian
      Regional Tobacco Industry Science Team (ARTIST), whose membership grew to include
      monopolies from Korea, China, Thailand, and Taiwan and a company from Indonesia.
      ARTIST was initially a vehicle for PM's strategies against anticipated calls for
      global smoke-free areas from a World Health Organization secondhand smoke study.
      ARTIST evolved through 2001 into a forum to present scientific and regulatory
      issues faced primarily by Philip Morris and other transnational tobacco
      companies. Philip Morris' goal for the organisation became to reach the external
      scientific and public health community and regulators in Asia. CONCLUSION: The
      Asian tobacco industry has changed from an environment of invasion by
      transnational tobacco companies to an environment of participation with Philip
      Morris' initiated activities. With this participation, tobacco control efforts in
      Asia face new challenges as Philip Morris promotes and integrates its scientific
      and regulatory agenda into the local Asian tobacco industry. As the local Asian
      tobacco monopolies and companies can have direct links with their governments,
      future implementation of effective tobacco control may be at odds with national
      priorities.

PMID- 15564215
TI  - "A phony way to show sincerity, as we all well know": tobacco industry lobbying
      against tobacco control in Hong Kong.
AB  - OBJECTIVE: To examine the tobacco industry's efforts to influence public policy
      and block the legislative process on tobacco control in Hong Kong, 1973 to 1997.
      METHOD: Systematic review of relevant tobacco industry documents made public via
      the Master Settlement Agreement. RESULTS: The tobacco industry in Hong Kong has
      sought to manipulate the policymaking process and delay the introduction of
      tobacco control legislation in Hong Kong from at least 1973. The industry ensured
      that each of the government's initial meagre steps toward tobacco control were
      delayed and thwarted by drawn out "cooperation" followed by voluntary concessions
      on issues the industry regarded as minor. By the 1980s the government had became
      increasingly active in tobacco control and introduced a number of initiatives,
      resulting in some of the tightest legislative restrictions on smoking in Asia.
      The tobacco industry was successful in thwarting only one of these initiatives.
      CONCLUSIONS: Throughout the 1980s and 1990s two factors played a significant role
      in hindering the tobacco industry from successfully blocking policy initiatives:
      a growing political imperative, and an active and sophisticated tobacco control
      movement. Political will to promote public health and a strong tobacco control
      advocacy presence can enable governments to resist the enormous pressure exerted
      upon them by multinational tobacco companies.

PMID- 15564216
TI  - "Asian yuppies...are always looking for something new and different": creating a
      tobacco culture among young Asians.
AB  - OBJECTIVE: To identify and analyse the themes employed by the Asian based
      transnational tobacco companies to construct a tobacco culture among Asian young
      men and women. METHODS: Systematic review of relevant tobacco industry documents
      made public through the Master Settlement Agreement. RESULTS: The industry
      utilised six vehicles and themes to construct a tobacco culture in Asia: music,
      entertainment (including nightclubs, discos, and movies), adventure, sport
      (including motorsports, soccer, and tennis), glamour (beauty and fashion), and
      independence. CONCLUSIONS: The tobacco industry set about constructing a tobacco
      culture that sought to make smoking desirable, even normal, for young men and
      women. Understanding the way industry constructed this culture provides insights
      into ways that culture might now be challenged. Countering the transnational
      nature of many activities will require coordinated effort at the international,
      regional, and national levels. Implementation of the Framework Convention on
      Tobacco Control (FCTC) will be a powerful tool in this process. All nations
      throughout Asia are encouraged to support the FCTC and its broad protocols
      addressing advertising and sponsorship. Measures are also required to
      disassociate smoking from progress in sex equality.

PMID- 15564217
TI  - "Asia is now the priority target for the world anti-tobacco movement": attempts
      by the tobacco industry to undermine the Asian anti-smoking movement.
AB  - STUDY OBJECTIVE: To identify and examine the strategies utilised by multinational
      tobacco companies to undermine and discredit key anti-tobacco activists and
      organisations in the Asian region. METHOD: A series of case studies drawing upon
      material gathered through systematic reviews of internal tobacco industry
      documents. DATE SOURCES: Tobacco industry documents made public as part of the
      settlement of the Minnesota Tobacco Trial and the Master Settlement Agreement.
      RESULTS: The industry sought to identify, monitor, and isolate key individuals
      and organisations. The way industry went about fulfilling this mandate in the
      Asian region is discussed. Industry targetted individuals and agencies along with
      the region's primary anti-smoking coalition. CONCLUSIONS: Attack by multinational
      tobacco companies is a virtual quid pro quo for any individual or agency
      seriously challenging industry practices and policies. Understanding their
      tactics allows anticipatory strategies to be developed to minimise the
      effectiveness of these attacks.

PMID- 15564218
TI  - Industry sponsored youth smoking prevention programme in Malaysia: a case study
      in duplicity.
AB  - OBJECTIVE: To review tobacco company strategies of using youth smoking prevention
      programmes to counteract the Malaysian government's tobacco control legislation
      and efforts in conducting research on youth to market to them. METHODS:
      Systematic keyword and opportunistic website searches of formerly private
      internal industry documents. Search terms included Malay, cmtm, jaycees, YAS, and
      direct marketing; 195 relevant documents were identified for this paper. RESULTS:
      Industry internal documents reveal that youth anti-smoking programmes were
      launched to offset the government's tobacco control legislation. The programme
      was seen as a strategy to lobby key politicians and bureaucrats for support in
      preventing the passage of legislation. However, the industry continued to conduct
      research on youth, targeted them in marketing, and considered the teenage market
      vital for its survival. Promotional activities targeting youth were also carried
      out such as sports, notably football and motor racing, and entertainment events
      and cash prizes. Small, affordable packs of cigarettes were crucial to reach new
      smokers. CONCLUSION: The tobacco industry in Malaysia engaged in duplicitous
      conduct in regard to youth. By buying into the youth smoking issue it sought to
      move higher on the moral playing field and strengthen its relationship with
      government, while at the same time continuing to market to youth. There is no
      evidence that industry youth smoking prevention programmes were effective in
      reducing smoking; however, they were effective in diluting the government's
      tobacco control legislation.

PMID- 15564219
TI  - "Care and feeding": the Asian environmental tobacco smoke consultants programme.
AB  - STUDY OBJECTIVE: To review the tobacco industry's Asian environmental tobacco
      smoke (ETS) consultants programme, focusing on three key nations: China, Hong
      Kong, and Malaysia. METHODS: Systematic keyword and opportunistic website
      searches of formerly private internal industry documents. MAIN RESULTS: The
      release of the 1986 US Surgeon General's report on second hand smoke provoked
      tobacco companies to prepare for a major threat to their industry. Asian
      programme activities included conducting national/international symposiums,
      consultant "road shows" and extensive lobbying and media activities. The industry
      exploited confounding factors said to be unique to Asian societies such as diet,
      culture and urban pollution to downplay the health risks of ETS. The industry
      consultants were said to be "..prepared to do the kinds of things they were
      recruited to do". CONCLUSIONS: The programme was successful in blurring the
      science on ETS and keeping the controversy alive both nationally and
      internationally. For the duration of the project, it also successfully dissuaded
      national policy makers from instituting comprehensive bans on smoking in public
      places.

PMID- 15564220
TI  - A mire of highly subjective and ineffective voluntary guidelines: tobacco
      industry efforts to thwart tobacco control in Malaysia.
AB  - OBJECTIVE: To describe tobacco industry efforts in Malaysia to thwart government
      efforts to regulate tobacco promotion and health warnings. METHODS: Systematic
      keyword and opportunistic website searches of formerly private tobacco industry
      internal documents made available through the Master Settlement Agreement and
      secondary websites; relevant information from news articles and financial
      reports. RESULTS: Commencing in the 1970s, the industry began to systematically
      thwart government tobacco control. Guidelines were successfully promoted in the
      place of legislation for over two decades. Even when the government succeeded in
      implementing regulations such as health warnings and advertising bans they were
      compromised and acted effectively to retard further progress for years to come.
      CONCLUSION: Counter-measures to delay or thwart government efforts to regulate
      tobacco were initiated by the industry. Though not unique to Malaysia, the main
      difference lies in the degree to which strategies were used to successfully
      counter stringent tobacco control measures between 1970 and 1995.

PMID- 15564221
TI  - "The world's most hostile environment": how the tobacco industry circumvented
      Singapore's advertising ban.
AB  - OBJECTIVE: To review how tobacco transnational companies conducted their business
      in the hostile environment of Singapore, attempting to counter some of the
      government's tobacco control measures; to compare the Malaysian and the
      Singaporean governments' stance on tobacco control and the direct bearing of this
      on the way the tobacco companies conduct their business. METHODS: Systematic
      keyword and opportunistic website searches of formerly private internal industry
      documents. RESULTS: The comprehensive prohibition on advertising did not prevent
      the companies from advertising cigarettes to Singaporeans. Both British American
      Tobacco and Philip Morris used Malaysian television to advertise into Singapore.
      To launch a new brand of cigarettes, Alpine, Philip Morris used a non-tobacco
      product, the Alpine wine cooler. Other creative strategies such as innovative
      packaging and display units at retailers were explored to overcome the
      restrictions. Philip Morris experimented with developing a prototype cigarette
      using aroma and sweetened tipping paper to target the young and health conscious.
      The industry sought to weaken the strong pack warnings. The industry distributed
      anti-smoking posters for youth to retailers but privately salivated over their
      market potential.

PMID- 15564222
TI  - A "clean cigarette" for a clean nation: a case study of Salem Pianissimo in
      Japan.
AB  - OBJECTIVE: To illustrate, through internal industry documents, how RJ Reynolds
      exploited the concerns of the Japanese society about cleanliness to market the
      concept of cleaner, implicitly healthier cigarettes in Japan. DESIGN: Systematic
      keyword and opportunistic website searches of formerly private internal industry
      documents. RESULTS: Industry documents show that RJ Reynolds developed marketing
      plans based upon their cultural assumptions of Japanese people as fastidious
      about hygiene and manners, and with relatively high penchants to try new
      products. RJ Reynolds found there was also a growing concern for health, the
      environment, and smokers were conscious about annoying others. Deodorised
      consumer products were one of Japan's biggest trends. These characteristics
      presented RJ Reynolds with a profitable formula for marketing Salem Pianissimo, a
      clean cigarette with less smell and smoke. Salem Pianissimo, a 100 mm cigarette
      claiming to contain 1 mg tar and 0.1 mg nicotine, targeted women since menthol
      cigarettes were popular among 18-24 year old female smokers, although Japan's law
      prohibited those below 20 years to smoke and the tobacco industry had a voluntary
      code disallowing advertising to women and youth. CONCLUSION: RJ Reynolds
      successfully launched its clean cigarette, Salem Pianissimo, in Japan aiming to
      exploit perceived cultural characteristics such as a penchant for cleanliness, an
      eagerness to try new products, and social harmony.

PMID- 15564223
TI  - The tobacco industry's accounts of refining indirect tobacco advertising in
      Malaysia.
AB  - OBJECTIVE: To explore tobacco industry accounts of its use of indirect tobacco
      advertising and trademark diversification (TMD) in Malaysia, a nation with a
      reputation for having an abundance of such advertising. METHODS: Systematic
      keyword and opportunistic website searches of formerly private tobacco industry
      internal documents made available through the Master Settlement Agreement.
      RESULTS: 132 documents relevant to the topic were reviewed. TMD efforts were
      created to advertise cigarettes after advertising restrictions on direct
      advertising were imposed in 1982. To build public credibility the tobacco
      companies set up small companies and projected them as entities independent of
      tobacco. Each brand selected an activity or event such as music, travel, fashion,
      and sports that best suited its image. RJ Reynolds sponsored music events to
      advertise its Salem brand while Philip Morris used Marlboro World of Sports since
      advertising restrictions prevented the use of the Marlboro man in broadcast
      media. Despite a ban on tobacco advertisements in the mass media, tobacco
      companies were the top advertisers in the country throughout the 1980s and 1990s.
      The media's dependence on advertising revenue and support from the ruling elite
      played a part in delaying efforts to ban indirect advertising. CONCLUSION:
      Advertising is crucial for the tobacco industry. When faced with an advertising
      ban they created ways to circumvent it, such as TMDs.

PMID- 15564224
TI  - The Philippine tobacco industry: "the strongest tobacco lobby in Asia".
AB  - OBJECTIVE: To highlight revelations from internal tobacco industry documents
      about the conduct of the industry in the Philippines since the 1960s. Areas
      explored include political corruption, health, employment of consultants,
      resisting pack labelling, and marketing and advertising. METHODS: Systematic
      keyword Minnesota depository website searches of tobacco industry internal
      documents made available through the Master Settlement Agreement. RESULTS: The
      Philippines has long suffered a reputation for political corruption where
      collusion between state and business was based on the exchange of political
      donations for favourable economic policies. The tobacco industry was able to
      limit the effectiveness of proposed anti-tobacco legislation. A prominent
      scientist publicly repudiated links between active and passive smoking and
      disease. The placement of health warning labels was negotiated to benefit the
      industry, and the commercial environment allowed it to capitalise on their
      marketing freedoms to the fullest potential. Women, children, youth, and the poor
      have been targeted. CONCLUSION: The politically laissez faire Philippines
      presented tobacco companies with an environment ripe for exploitation. The
      Philippines has seen some of the world's most extreme and controversial forms of
      tobacco promotion flourish. Against international standards of progress, the
      Philippines is among the world's slowest nations to take tobacco control
      seriously.

PMID- 15564225
TI  - "If we can just 'stall' new unfriendly legislations, the scoreboard is already in
      our favour": transnational tobacco companies and ingredients disclosure in
      Thailand.
AB  - OBJECTIVES: To review the strategies employed by overseas cigarette manufacturers
      operating in Thailand to obstruct the passage and subsequent enforcement of
      national public health legislation, specifically the ingredients disclosure
      provision of the 1992 Tobacco Products Control Act. METHODS: Analysis of
      previously confidential tobacco industry documents relevant to non-compliance
      with the ingredients disclosure legislation. RESULTS: Requirement for disclosure
      of ingredients contained in cigarettes contained in the Tobacco Products Control
      Act was identified by transnational tobacco companies (TTCs) not only as a
      significant threat to their operations in Thailand, but as a dangerous global
      precedent. Industry documents reveal a determined campaign to block, stall, or
      amend the proposed regulation during the legislative process. Industry
      representatives petitioned the Ministry of Health to revise the requirement from
      by brand disclosure to a more palatable by company submission. Strategies were
      adapted in the wake of the passage of the Act. Most significantly, the industry
      in concert with embassies in Bangkok threatened the Thai government with appeals
      to international trade bodies on the grounds of violation of international
      agreements. Industry documents also reveal that as submission of ingredient lists
      appeared unavoidable, leading companies operating in Thailand endeavoured to
      confound the disclosure requirement by disguising ingredients and reformulating
      brand recipes. CONCLUSIONS: The evidence presented highlights the importance of
      ingredients regulation and demonstrates how health policy can be transformed
      during its implementation. A greater understanding of trade agreements emerges as
      a priority for global tobacco control.

PMID- 15564226
TI  - Breaking and re-entering: British American Tobacco in China 1979-2000.
AB  - OBJECTIVES: To analyse the strategy used by British American Tobacco (BAT) to re
      enter the Chinese market from 1979 to 2000 after historically dominating the
      market before the 1950s. DESIGN: Analysis of tobacco industry document files to
      date available only on-site at the Guildford Depository operated by BAT. An
      additional search of recent documents related to BAT, placed in the Minnesota
      Depository, was also carried out. RESULTS: BAT has been committed to regaining
      its historically dominant position in China since the country reopened to foreign
      companies in 1979. Initially, BAT remained cautious relative to competitors in
      seeking joint ventures, finding market access hindered by bureaucratic
      complexity, restrictions on foreign investment and imports quotas, and later an
      advertising ban. Instead, the documents suggest BAT strongly relied on illegal
      imports to expand market presence of State Express 555 and other key brands. It
      was only when risks to contraband sales increased that the company made greater
      efforts to establish a legal presence in the country. Attempts to stress the long
      history of BAT in China and a proclaimed commitment to corporate social
      responsibility have been used to facilitate later negotiations. CONCLUSION: China
      has remained relatively closed to transnational tobacco companies (TTCs) during
      its transition to a market economy, maintaining a firm grip over foreign
      investment and imports. Nonetheless, BAT has circumvented such restrictions
      through illegal imports and exploitation of inconsistencies in the local
      enforcement of advertising bans. Governments need to understand and address the
      full range of market entry tactics by TTCs in order to ensure effective tobacco
      control.

PMID- 15564227
TI  - Competing with kreteks: transnational tobacco companies, globalisation, and
      Indonesia.
AB  - OBJECTIVE: To examine the strategies employed by transnational tobacco companies
      (TTCs) to compete more effectively compete with the dominant kretek manufacturers
      in Indonesia, and to consider implications of their failure. METHODS: Systematic
      analysis of corporate documents obtained from British American Tobacco's (BAT's)
      Guildford depository and from industry and tobacco control websites document
      collections. RESULTS: The limited progress of the TTCs in Indonesia is best
      explained by the distinctive political economy of its tobacco industry. Though
      effective when collaborating on regulatory issues of mutual interest, TTCs have
      been less able than kretek manufacturers to exercise political influence where
      their interests conflict. Global strategies of TTCs have undergone significant
      local adaptation in attempting to compete in this distinctive environment. While
      maintaining uniformity in core brand attributes, TTCs have sought to reconcile
      international imagery with local norms, particularly to appeal to women. BAT
      unsuccessfully attempted to develop clove based products that imitated the appeal
      of kreteks, withdrawn following concerns about exposing the company to charges of
      operating double standards. CONCLUSIONS: The documents presented highlight the
      complexity of the global tobacco industry. Tobacco control efforts need to
      address more effectively the ongoing impact of kreteks while recognising the
      distinctive threats posed by TTCs.

PMID- 15564228
TI  - How doctors discuss major interventions with high risk patients: an observational
      study.
AB  - OBJECTIVE: To investigate the difficulties doctors face in discussing treatment
      options with patients with acute, life threatening illness and major
      comorbidities. DESIGN: Observational study of doctor-patient interviews based on
      a standardised clinical scenario involving high risk surgery in a hypothetical
      patient (played by an actor) with serious comorbidities. PARTICIPANTS: 30 trainee
      doctors 3-5 years after graduation. MAIN OUTCOME MEASURES: Adequacy of coverage
      of various aspects was scored from 3 (good) to 0 (not discussed). RESULTS: The
      medical situation was considered to be well described (median score 2.7
      (interquartile range 2.1-3.0)), whereas the patient's functional status, values,
      and fears were poorly or minimally addressed (scores 0.5 (0.0-1.0), 0.5 (0.0
      1.0), and 0.0 (0.0-1.5), respectively; all P < 0.001 v score for describing the
      medical situation). Twenty nine of the doctors indicated that they wished to
      include the patient's family in the discussion, but none identified a preferred
      surrogate decision maker. Six doctors suggested that the patient alone should
      speak with his family to reach a decision without the doctor being present. The
      doctors were reluctant to give advice, despite it being directly requested: two
      doctors stated that a doctor could not give advice, while 17 simply restated the
      medical risks, without advocating any particular course. Of the 11 who did offer
      advice, eight advocated intervention. CONCLUSIONS: Doctors focused on technical
      medical issues and placed much less emphasis on patient issues such as functional
      status, values, wishes, and fears. This limits doctors' ability to offer suitable
      advice about treatment options. Doctors need to improve their communication
      skills in this difficult but common clinical situation.

PMID- 15564229
TI  - Randomised controlled trial of an occupational therapy intervention to increase
      outdoor mobility after stroke.
AB  - OBJECTIVE: To evaluate an occupational therapy intervention to improve outdoor
      mobility after stroke. DESIGN: Randomised controlled trial. SETTING: General
      practice registers, social services departments, a primary care rehabilitation
      service, and a geriatric day hospital. PARTICIPANTS: 168 community dwelling
      people with a clinical diagnosis of stroke in previous 36 months: 86 were
      allocated to the intervention group and 82 to the control group. INTERVENTIONS:
      Leaflets describing local transport services for disabled people (control group)
      and leaflets with assessment and up to seven intervention sessions by an
      occupational therapist (intervention group). MAIN OUTCOME MEASURES: Responses to
      postal questionnaires at four and 10 months: primary outcome measure was response
      to whether participant got out of the house as much as he or she would like, and
      secondary outcome measures were response to how many journeys outdoors had been
      made in the past month and scores on the Nottingham extended activities of daily
      living scale, Nottingham leisure questionnaire, and general health questionnaire.
      RESULTS: Participants in the treatment group were more likely to get out of the
      house as often as they wanted at both four months (relative risk 1.72, 95%
      confidence interval 1.25 to 2.37) and 10 months (1.74, 1.24 to 2.44). The
      treatment group reported more journeys outdoors in the month before assessment at
      both four months (median 37 in intervention group, 14 in control group: P < 0.01)
      and 10 months (median 42 in intervention group, 14 in control group: P < 0.01).
      At four months the mobility scores on the Nottingham extended activities of daily
      living scale were significantly higher in the intervention group, but there were
      no significant differences in the other secondary outcomes. No significant
      differences were observed in these measures at 10 months. CONCLUSION: A targeted
      occupational therapy intervention at home increases outdoor mobility in people
      after stroke.

PMID- 15564230
TI  - Incidence of Haemophilus influenzae type b meningitis during 18 years of vaccine
      use: observational study using routine hospital data.

PMID- 15564231
TI  - The white paper on public health.

PMID- 15564232
TI  - Angiotensin receptor blockers and myocardial infarction.

PMID- 15564233
TI  - The Mexico summit on health research 2004.

PMID- 15564234
TI  - Standards for Better Health: fit for purpose?

PMID- 15564235
TI  - Case management and community matrons for long term conditions.

PMID- 15564236
TI  - FDA is incapable of protecting US "against another Vioxx".

PMID- 15564237
TI  - US pro-choice groups prepare for fight over Supreme Court nominee.

PMID- 15564238
TI  - TV programme raises fresh allegations about MMR doctor.

PMID- 15564239
TI  - Public interest group accuses FDA of trying to discredit whistleblower.

PMID- 15564240
TI  - Drug maker urges group to lobby FDA on testosterone for women.

PMID- 15564241
TI  - Review of child care cases finds few instances that raise "serious doubt".

PMID- 15564243
TI  - Landmine casualties are falling, but the wounded need more help.

PMID- 15564244
TI  - Drug industry is not tackling threats to public health, says WHO.

PMID- 15564245
TI  - Six GPs who signed cremation forms for Shipman face GMC.

PMID- 15564246
TI  - Women are increasingly affected by AIDS epidemic, report shows.

PMID- 15564248
TI  - Inquiry finds that Gulf war veterans face extra burden of disease.

PMID- 15564249
TI  - Patients with head or neck cancer should be treated at specialist centres.

PMID- 15564252
TI  - NICE issues guideline to prevent falls in elderly people.

PMID- 15564254
TI  - UN delays decision on human cloning.

PMID- 15564256
TI  - UK report warns of continued increase in HIV infection.

PMID- 15564257
TI  - Mexico summit calls for greater commitment to health research.

PMID- 15564258
TI  - Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in
      patients given infliximab.

PMID- 15564259
TI  - Newly diagnosed hypothyroidism.

PMID- 15564260
TI  - Surgical management of metastatic inguinal lymphadenopathy.

PMID- 15564261
TI  - Infection in the preterm infant.

PMID- 15564262
TI  - Barriers to better care for people with AIDS in developing countries.

PMID- 15564263
TI  - Natural killer cells, miscarriage, and infertility.

PMID- 15564264
TI  - Olfactory detection of human bladder cancer by dogs: another cancer detected by
      "pet scan".

PMID- 15564265
TI  - Olfactory detection of human bladder cancer by dogs: cause or association?

PMID- 15564266
TI  - Colonoscopy completion rates: should less successful endoscopists be removed or
      retrained?

PMID- 15564267
TI  - Colonoscopy completion rates: technologies have evolved.

PMID- 15564268
TI  - Epidemiology of preterm birth: delayed cord clamping used to be taught and
      practised.

PMID- 15564269
TI  - Completion lymphadenectomy may not increase in-transit disease in malignant
      melanoma.

PMID- 15564270
TI  - Life span and disability in Sweden and Russia: paper highlights poor health among
      Russian women.

PMID- 15564271
TI  - NICE and BHS guidelines on hypertension differ importantly.

PMID- 15564272
TI  - Infectious diseases in Iraq have international implications.

PMID- 15564273
TI  - Iodine deficiency in Papua New Guinea (sub-clinical iodine deficiency and salt
      iodization in the highlands of Papua New Guinea).
AB  - Data on the status about iodine nutrition in children in Papua New Guinea (PNG)
      are scarce. This study attempts to determine the mean daily per capita
      consumption of salt, the iodine content of salt in the households and retail
      shops and the urinary iodine concentration in children (6-12 years) in Hella
      Region, Southern Highland Province (SHP), PNG. The mean daily consumption of salt
      was 2.62 +/- 1.29 g. The iodine content of salt was >30 p.p.m. in 95 per cent of
      households and 100 per cent of retail shops. The median urinary iodine
      concentration of 48.0 mg/l for all the children indicates moderate iodine
      deficiency. The median urinary iodine concentrations for the male (67.0 mg/l) and
      female (44.0 mg/l) children indicate mild and moderate iodine deficiency,
      respectively. 68.42 per cent of the male and 81.82 per cent of the female
      children have urinary iodine concentration <100 mg/l, indicating that iodine
      deficiency is a potential public health problem in the Hella region. These
      results indicate a need for further assessment of the implementation of the
      universal salt iodization strategy for the elimination of iodine deficiency in
      the SHP, PNG.

PMID- 15564274
TI  - Tetanus in an unvaccinated child in the United Kingdom: case report.
AB  - Tetanus is a serious infectious disease that is associated with high morbidity
      and mortality. It is uncommon in developed countries like the United Kingdom due
      to widespread immunization. However, cases are still being reported in children
      who are not immunized. We report a case of an 8-year-old Asian boy who had missed
      his childhood vaccinations but had been living in the United Kingdom for 3 years.
      He presented with trismus and muscle spasms needing ventilation in Paediatric
      Intensive Care for 3 weeks. The case highlights the importance of vaccinating
      newly arrived children.

PMID- 15564275
TI  - Does primary care referral to an exercise programme increase physical activity
      one year later? A randomized controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of a primary care referral scheme on
      increasing physical activity at 1 year from referral. Design Two-group randomized
      controlled trial recruiting primary care referrals to a borough-based exercise
      scheme. Setting A local authority borough in the north-west of England.
      Participants 545 patients defined as sedentary by a primary care practitioner.
      Intervention Referral to a local-authority exercise referral scheme and written
      information compared with written information only. Main outcome measures Meeting
      physical activity target at 12 months following referral, with a secondary
      outcome measured at 6 months from referral. RESULTS: At 12 months, a non
      significant increase of 5 per cent was observed in the intervention compared with
      control group, for participation in at least 90 minutes of moderate/vigorous
      activity per week (25.8 versus 20.4 per cent, OR 1.45, 0.84 to 2.50, p = 0.18).
      At 6 months, a 10 per cent treatment effect was observed which was significant
      (22.6 versus 13.6 per cent, OR 1.67, 1.08 to 2.60, p = 0.05). The intervention
      increased satisfaction with information but this did not influence adherence with
      physical activity. CONCLUSION: Community-based physical activity referral schemes
      have some impact on reducing sedentary behaviour in the short-term, but which is
      unlikely to be sustained and lead to benefits in terms of health.

PMID- 15564276
TI  - How accurate are Townsend Deprivation Scores as predictors of self-reported
      health? A comparison with individual level data.
AB  - OBJECTIVES: To determine the accuracy of area based Townsend Deprivation Scores
      (TDSs) as proxies for individual level deprivation and to compare the ability of
      TDSs and individual level measures of deprivation to predict selfreported health.
      METHODS: Using data from a self completed health and behaviour survey sent to a
      random sample of households in Newcastle upon Tyne, UK, the ability of TDSs,
      calculated at the enumeration district and ward level, to predict selfreported
      health was compared to that of an individual level measure of deprivation similar
      to TDSs. The correlation between each of these measures of deprivation was also
      investigated. RESULTS: Enumeration district TDSs were similarly predictive of
      self-reported health as the individual level measure of deprivation. Ward-level
      TDSs showed a much weaker association with self-reported health. Although
      statistically significant, no deprivation measure accounted for more than 3 per
      cent of the variation in self-reported health. There was a strong correlation
      between the individual level measure of deprivation and enumeration district, but
      not ward-level TDSs. CONCLUSIONS: TDSs calculated at the enumeration district
      level are strongly correlated with a similar measure of deprivation calculated at
      the individual level and are similarly predictive of health. This is not the case
      for TDSs calculated at the ward level. Enumeration district TDSs are good proxies
      for individual level deprivation in Newcastle upon Tyne. This may not be the case
      in more mobile populations.

PMID- 15564277
TI  - The epidemiology and management of self-harm amongst adults in England.
AB  - BACKGROUND: Previous research into the epidemiology and management of self-harm
      has been largely based in centres with a special interest in this behaviour or
      focused on hospital admissions only. There are no national data on the
      characteristics and management of people presenting to hospital following self
      harm. METHODS: Data were collected from 8-week service audits carried out in a
      stratified random sample of 31 general hospitals in England. RESULTS: 4033
      episodes of self-harm resulting in presentation to Accident and Emergency
      Departments were identified. Overdose alone accounted for 79 per cent of
      episodes, 80 per cent of presentations were outside normal office hours (9 am - 5
      pm, Monday to Friday) and the peak period of attendance was from 8 pm to 2 am. In
      only 56 per cent of episodes was a specialist psychosocial assessment conducted
      prior to discharge and less than half (46 per cent) led to admission to a
      hospital bed. Psychiatric admission occurred in 10 per cent. Episodes involving
      older subjects (>45 years) and those using methods other than laceration or
      overdose were the most likely to lead to assessment and admission. CONCLUSIONS:
      Non-fatal self-harm is one of the strongest predictors of suicide, yet nearly
      half of all hospital attendances in England following self-harm do not lead to a
      specialist assessment. Patterns of service provision should take account of the
      observation that most self-harm attendances occur outside normal working hours
      and those at greatest risk of repetition are the least likely to receive
      assessments.

PMID- 15564278
TI  - Regional surveillance of accident and emergency department attendances:
      experiences from the West Midlands.
AB  - Information is collected on every patient that attends accident and emergency (A
      and E). However, there is currently no central collection of these data. In 1999
      it was decided to collect data on all A and E attendances in the West Midlands
      region. All 21 hospitals with 24 h A and E departments were asked to submit data
      to the Surveillance Centre at the University of Birmingham. To date, 19 hospitals
      have submitted data but the formats vary leading to a substantial amount of data
      processing. There are several limitations to the data set, for example a lack of
      information on the reasons for attendance. Despite this, routinely collected A
      and E data have great potential for surveillance and the data have been used in
      original research and to guide local policy. The West Midlands system is the
      largest source of A and E data in the United Kingdom. This information is of use
      to a wide range of organizations.

PMID- 15564279
TI  - High rates of primary care and emergency department use among injection drug
      users in Vancouver.
AB  - BACKGROUND: Frequent use of emergency rooms by injection drug users (IDUs) has
      been attributed to a lack of access to primary care and barriers to health
      services. Using a community-based sample of IDUs, we examined rates of primary
      care and emergency room use among IDUs and identified correlates of frequent
      emergency department use. METHODS: From January to November 2003, we enrolled
      IDUs into a prospective cohort study involving a baseline questionnaire,
      comprehensive retrospective and prospective health record linkages. We examined
      rates of primary care and emergency department utilization, and diagnoses upon
      arrival in the emergency room. Logistic regression was used to determine factors
      independently associated with frequent emergency room use. RESULTS: Of the 883
      IDUs included in this analysis, 687 (78 per cent) accessed a primary care clinic
      in the previous year, while 528 (60 per cent) participants accessed the emergency
      room (ER) during the years 2002 and 2003. Abscesses, cellulitis and other skin
      infections accounted for the greatest proportion of ER use. Factors independently
      associated with frequent ER use included: frequent crystal methamphetamine
      injection (AOR = 2.4, 95 per cent CI: 1.0-5.6); non-fatal overdose (AOR = 2.1, 95
      per cent CI: 1.4-3.3); HIV-positive status (AOR = 1.5, 95 per cent CI: 1.1-2.1),
      having been physically assaulted (AOR = 1.5, 95 per cent CI: 1.1-2.1); and
      primary care utilization (AOR = 1.5, 95 per cent CI: 1.0-2.1). DISCUSSION: high
      rates of ER use were observed among IDUs, despite high rates of primary care use
      among this same population. ER use was due primarily to preventable injection
      related complications that are less amenable to primary care interventions, and
      therefore educational and prevention efforts that encourage and enable sterile
      injection practices should be promoted.

PMID- 15564280
TI  - Incidence of meningitis and of death from all causes among users of cochlear
      implants in the United Kingdom.
AB  - BACKGROUND: During 2002, there was an increase in reports of bacterial meningitis
      among people with cochlear implants in Europe and North America. One model of
      implant, which included a space-occupying 'positioner', was recalled.
      Implantation of a positioner was shown to be a risk factor for meningitis among
      children in the United States. The situation in the United Kingdom was not known.
      METHODS: We ascertained the cohort of people who had received cochlear implants
      with intra-cochlear electrodes in UK hospitals prior to 1 October 2002 and were
      permanently resident in the United Kingdom. We compared the incidence of
      meningitis, and the causes and incidence of death from all causes, between the
      cohort and reference populations. RESULTS: Of 1851 children (66 with
      positioners), none had contracted meningitis. Neither the incidence rate of
      meningitis, nor the cumulative mortality from all causes, differed significantly
      between implanted children and values expected for the general population. Of
      1779 adults (139 with positioners), five had contracted meningitis with three
      fatalities. No case of meningitis involved a positioner and four of the cases,
      including the fatalities, possessed risk factors unrelated to implantation.
      Although the incidence rate of meningitis was significantly higher in implanted
      adults than the general population, cumulative mortality from all causes was
      never higher, and was significantly lower at some time points after implantation.
      CONCLUSION: Specific evidence of the association between bacterial meningitis and
      implantation with a positioner that arose in the United States and mainland
      Europe during 2002 has not been found in the United Kingdom.

PMID- 15564281
TI  - Identification of ON-OFF direction-selective ganglion cells in the mouse retina.
AB  - We identified the ON-OFF direction-selective ganglion cells (DSGCs) in the mouse
      retina and characterized their physiological, morphological and pharmacological
      properties. These cells showed transient responses to the onset and termination
      of a stationary flashing spot, and strong directional selectivity to a moving
      rectangle. Application of various pharmacological reagents demonstrated that the
      ON-OFF DSGCs in the mouse retina utilize a similar array of transmitters and
      receptors to compute motion direction to their counterparts in the rabbit retina.
      Voltage clamp recording showed that ON-OFF DSGCs in the mouse retina receive a
      larger inhibitory input when the stimulus is moving in the null direction and a
      larger excitatory input when the stimulus is moving in the preferred direction.
      Finally, intracellular infusion of neurobiotin revealed a bistratified dendritic
      field with recursive dendrites forming loop-like structures, previously
      classified as RG(D2) by morphology. Overall, the ON-OFF DSGCs in the mouse retina
      exhibit almost identical properties to their counterparts in the rabbit retina,
      indicating that the mechanisms for computing motion direction are conserved from
      mouse to rabbit, and probably also to higher mammals. This first detailed
      characterization of ON-OFF DSGCs in the mouse retina provides fundamental
      information for further study of maturation and regulation of the neuronal
      circuitry underlying computation of direction.

PMID- 15564283
TI  - Volume sensitivity of the bestrophin family of chloride channels.
AB  - Bestrophins are a newly identified family of Cl(-) channels. Mutations in the
      founding member of the family, human bestrophin-1 (hBest1), are responsible for a
      form of early onset macular degeneration called Best vitelliform macular
      dystrophy. The link between dysfunction of hBest1 and macular degeneration
      remains unknown. Because retinal pigmented epithelium (RPE) cells may be
      subjected to varying osmotic pressure due to light-dependent changes in the ionic
      composition of the subretinal space and because RPE cells may undergo large
      volume changes during phagocytosis of shed photoreceptor discs, we investigated
      whether bestrophin currents were affected by cell volume. When hBest1 and mBest2
      were overexpressed in HEK 293, HeLa, and ARPE-19 cells, a new Ca(2+)-activated
      Cl(-) current appeared. This current was very sensitive to cell volume. A 20%
      increase in extracellular osmolarity caused cell shrinkage and a approximately 70
      80% reduction in bestrophin current. Decreases in extracellular osmolarity
      increased the bestrophin currents slightly, but this was difficult to quantify
      due to simultaneous activation of endogenous volume-regulated anion channel
      (VRAC) current. To determine whether a similar current was present in mouse RPE
      cells, the effect of hyperosmotic solutions on isolated mouse RPE cells was
      examined. Mouse RPE cells exhibited an endogenous Cl(-) current that resembled
      the expressed hBest1 in that it was decreased by hypertonic solution. We conclude
      that bestrophins are volume sensitive and that they could play a novel role in
      cell volume regulation of RPE cells.

PMID- 15564282
TI  - The effects of intracellular Ca2+ on cardiac K+ channel expression and activity:
      novel insights from genetically altered mice.
AB  - We tested the hypothesis that chronic changes in intracellular Ca(2+) (Ca(2+)(i))
      can result in changes in ion channel expression; this represents a novel
      mechanism of crosstalk between changes in Ca(2+) cycling proteins and the cardiac
      action potential (AP) profile. We used a transgenic mouse with cardiac-specific
      overexpression of sarcoplasmic reticulum Ca(2+) ATPase (SERCA) isoform 1a
      (SERCA1a OE) with a significant alteration of SERCA protein levels without
      cardiac hypertrophy or failure. Here, we report significant changes in the
      expression of a transient outward K(+) current (I(to,f)), a slowly inactivating
      K(+) current (I(K,slow)) and the steady state current (I(SS)) in the transgenic
      mice with resultant prolongation in cardiac action potential duration (APD)
      compared with the wild-type littermates. In addition, there was a significant
      prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice.
      The electrophysiological changes, which correlated with changes in Ca(2+)(i),
      were further corroborated by measuring the levels of ion channel protein
      expression. To recapitulate the in vivo experiments, the effects of changes in
      Ca(2+)(i) on ion channel expression were further tested in cultured adult and
      neonatal mouse cardiac myocytes. We conclude that a primary defect in Ca(2+)
      handling proteins without cardiac hypertrophy or failure may produce profound
      changes in K(+) channel expression and activity as well as cardiac AP.

PMID- 15564284
TI  - Ca2+-independent hypoxic vasorelaxation in porcine coronary artery.
AB  - To demonstrate a Ca(2+)-independent component of hypoxic vasorelaxation and to
      investigate its mechanism, we utilized permeabilized porcine coronary arteries,
      in which [Ca(2+)] could be clamped. Arteries permeabilized with beta-escin
      developed maximum force in response to free Ca(2+) (6.6 microm), concomitant with
      a parallel increase in myosin regulatory light chain phosphorylation (MRLC-P(i)),
      from 0.183 +/- 0.023 to 0.353 +/- 0.019 MRLC-P(i) (total light chain)(-1).
      Hypoxia resulted in a significant decrease in both force (-31.9 +/- 4.1% prior
      developed force) and MRLC-P(i) (from 0.353 to 0.280 +/- 0.023), despite constant
      [Ca(2+)] buffered by EGTA (4 mm). Forces developed in response to Ca(2+) (6.6
      microm), Ca(2+) (0.2 microm) + GTPgammaS (1 mM), or in the absence of Ca(2+)
      after treatment with ATPgammaS (1 mM), were of similar magnitude. Hypoxia also
      relaxed GTPgammaS contractures but importantly, arteries could not be relaxed
      after treatment with ATPgammaS. Permeabilization with Triton X-100 for 60 min
      also abolished hypoxic relaxation. The blocking of hypoxic relaxation after
      ATPgammaS suggests that this Ca(2+)-independent mechanism(s) may operate through
      alteration of MRLC-P(i) or of phosphorylation of the myosin binding subunit of
      myosin light chain phosphatase. Treatment with the Rho kinase inhibitor Y27632 (1
      microm) relaxed GTPgammaS and Ca(2+) contractures; but the latter required a
      higher concentration (10 microm) for consistent relaxation. Relaxations to N(2)
      and/or Y27632 averaged 35% and were not additive or dependent on order. Our data
      suggest that the GTP-mediated, Rho kinase-coupled pathway merits further
      investigation as a potential site of this novel, Ca(2+)-independent O(2)-sensing
      mechanism. Importantly, these results unambiguously show that hypoxia-induced
      vasorelaxation can occur in permeabilized arteries where the Ca(2+) is clamped at
      a constant value.

PMID- 15564285
TI  - "Fast" and "slow" muscle fibres in hindlimb muscles of adult rats regenerate from
      intrinsically different satellite cells.
AB  - Myosin heavy chain (MyHC) expression was examined in regenerating fast extensor
      digitorum longus (EDL) and slow soleus (SOL) muscles of adult rats. Myotoxic
      bupivacaine was injected into SOL and EDL and the muscles were either denervated
      or neuromuscularly blocked by tetrodotoxin (TTX) on the sciatic nerve. Three to
      10 or 30 days later, denervated SOL or EDL, or innervated but neuromuscularly
      blocked EDL received a slow 20 Hz stimulus pattern through electrodes implanted
      on the muscles or along the fibular nerve to EDL below the TTX block. In
      addition, denervated SOL and EDL received a fast 100 Hz stimulus pattern.
      Denervated EDL and SOL stimulated with the same slow stimulus pattern expressed
      different amounts of type 1 MyHC protein (8% versus 35% at 10 days, 13% versus
      87% at 30 days). Stimulated denervated and stimulated innervated (TTX blocked)
      EDL expressed the same amounts of type 1, 2A, 2X and 2B MyHC proteins. Cross
      sections treated for in situ hybridization and immunocytochemistry showed
      expression of type 1 MyHC in all SOL fibres but only in some scattered single or
      smaller groups of fibres in EDL. The results suggest that muscle fibres
      regenerate from intrinsically different satellite cells in EDL and SOL and within
      EDL. However, induction by different extrinsic factors arising in extracellular
      matrix or from muscle position and usage in the limb has not been excluded. No
      evidence for nerve-derived trophic influences was obtained.

PMID- 15564286
TI  - Initial results from a longitudinal international surveillance programme for
      anidulafungin (2003).
AB  - OBJECTIVES: This longitudinal study evaluated the in vitro activity of
      anidulafungin against 880 clinical yeast isolates and 68 mould isolates from 64
      medical centres in North America, Latin America and Europe. METHODS: MICs of
      anidulafungin, amphotericin B, 5-fluorocytosine, fluconazole, itraconazole,
      ketoconazole and voriconazole were determined using reference method (M27-A2)
      guidelines. The M38-A reference method was used for the filamentous fungi,
      including determination of minimum effective concentrations (MECs) of
      anidulafungin. RESULTS: Anidulafungin was more active when compared with
      fluconazole and itraconazole for Candida albicans (MIC(90), 0.06 mg/L), Candida
      tropicalis (MIC(90), 0.06 mg/L), Candida glabrata (MIC(90), 0.12 mg/L), Candida
      krusei (MIC(90), 0.06 mg/L) and Candida lusitaniae (MIC(90), 1 mg/L) as well as
      the less-often encountered yeast species. Anidulafungin was less active against
      Candida parapsilosis, Candida guilliermondii and Candida famata (MIC(50), 1-2
      mg/L). Anidulafungin also exhibited excellent activity against all Aspergillus
      spp. (MEC(90), < or =0.03 mg/L). Anidulafungin was also evaluated comparing two
      end point reading criteria and two incubation intervals. Data indicate that
      longer incubation periods do not significantly influence overall MIC ranges.
      These international surveillance results for anidulafungin confirm the activity
      observed in studies of smaller numbers of isolates.

PMID- 15564287
TI  - Incorporation of dUMP into DNA is a major source of spontaneous DNA damage, while
      excision of uracil is not required for cytotoxicity of fluoropyrimidines in mouse
      embryonic fibroblasts.
AB  - Uracil may arise in DNA as a result of deamination of cytosine or through
      incorporation of dUMP instead of dTMP during replication. We have studied the
      steady-state levels of uracil in the DNA of primary cells and mouse embryonic
      fibroblast (MEF) cell lines from mice deficient in the Ung uracil-DNA
      glycosylase. The results show that the levels of uracil in the DNA of Ung(-/-)
      cells strongly depend on proliferation, indicating that the uracil residues
      originate predominantly from misincorporation during replication. Treatment with
      5-fluoro-2'-deoxyuridine (5-FdUrd) or 5-fluorouracil (5-FU) gives rise to a dose
      dependent increase of uracil in Ung(-/-) MEFs (up to 1.5-fold) but not in wild
      type cells. Interestingly, Ung(-/-) MEFs accumulate AP-sites as well as uracil in
      response to 5-FdUrd but not to 5-FU. This accumulation of repair intermediates
      suggests a loss of tightly co-ordinated repair in the absence of Ung, and
      correlates with stronger inhibition of cell proliferation in response to 5-FdUrd,
      but not to 5-FU, in Ung(-/-) MEFs compared with wild-type cells. However, other
      cytotoxic effects of these fluoropyrimidines are comparable in both wild-type and
      Ung-deficient cells, demonstrating that excision of uracil from DNA by the Ung
      uracil-DNA glycosylase is not a prerequisite for obtaining cytotoxicity.

PMID- 15564288
TI  - Polymorphisms in XPD and TP53 and mutation in human lung cancer.
AB  - The pattern of somatic mutations in TP53 is distinct for particular cancers and
      carcinogenic exposures, providing clues to disease etiology, e.g. G:C-->T:A
      mutations in TP53 are more frequently observed in smoking-associated lung
      cancers. In order to investigate possible causes and mechanisms of lung cancer
      susceptibility differences, the TP53 gene was sequenced in a case-only study of
      lung cancers (206 men and 103 women). Our primary hypothesis was that the TP53
      mutation spectrum is influenced by polymorphisms in genes involved in DNA repair
      and apoptosis. We observed a TP53 mutation frequency in exons 5-8 of 25%.
      Functional polymorphisms in XPD (Asp312Asn, rs1799793 and Lys751Gln, rs1052559),
      a protein required for nucleotide excision repair and with roles in p53-mediated
      apoptosis, were modestly associated with G:C-->T:A mutations in TP53 in lung
      tumors [Asp/Asn312 + Asn/Asn312 and/or Lys/Gln751 + Gln/Gln751 versus Asp/Asp312
      + Lys/Lys751; odds ratio (OR) 2.73, 95% confidence interval (CI) 0.98-7.61],
      consistent with the role of this protein in repair of bulky carcinogen-DNA
      adducts. In addition, a TP53 polymorphism (Arg72Pro, rs1042522) with a known role
      in the efficiency of apoptosis was also associated with the presence of a TP53
      mutation (Pro/Arg72 or Pro/Pro72 versus Arg/Arg72; OR 2.25, 95% CI 1.21-4.17) or
      a G:C-->T:A mutation in TP53 (Pro/Arg72 or Pro/Pro72 versus Arg/Arg72; OR 2.42,
      95% CI 0.97-6.04). An interaction between the XPD variant alleles (Asn312 and
      Gln751) and the TP53 Pro72 allele was observed for TP53 mutations (any TP53
      mutation P(int) = 0.027, G:C-->T:A TP53 mutation P(int) = 0.041). The statistical
      interaction observed in our study is consistent with the observed biological
      interaction for XPD and p53 in nucleotide excision repair and apoptosis. In
      conclusion, differences in TP53 mutation spectra in lung tumors are associated
      with several genetic factors and may reflect differences in lung cancer
      susceptibility and carcinogenesis.

PMID- 15564289
TI  - The PPAR{gamma} Pro12Ala polymorphism and risk for incident sporadic colorectal
      adenomas.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the
      nuclear hormone receptor superfamily initially shown to be a key regulator of fat
      cell differentiation, can inhibit cell growth and induce apoptosis in colon cell
      lines. There are heterozygous loss of function mutations in the gene encoding
      PPARgamma in tumors from approximately 10% of human colon cancer patients. A
      common structural polymorphism has been detected in the PPARgamma gene at codon
      12 (Pro12Ala). We investigated the hypothesis that the PPARgamma Pro12Ala
      polymorphism is associated with colorectal adenoma risk in a recently concluded
      case-control study of incident sporadic colorectal adenomas (163 cases and 212
      controls). The multivariate-adjusted odds ratio (OR) for incident sporadic
      colorectal adenoma was 0.65 (95% CI 0.39-1.09) for those with the Pro12Ala or
      Ala12Ala genotype compared with those with the Pro12Pro genotype. Multivariate
      adjusted inverse associations with the Ala12 variant were more pronounced among
      those who were female (OR 0.36, 95% CI 0.18-0.75) or did not take non-steroidal
      anti-inflammatory drugs (OR 0.38, 95% CI 0.14-1.00). Marginally significant
      results were observed among those with a lower waist:hip ratio (OR 0.52, 95% CI
      0.24-1.12) or a lower body mass index (OR 0.46, 95% 0.20-1.05). Smoking was a
      very strong risk factor (OR 2.34, 95%CI 1.37-4.02) for colorectal adenoma among
      those with the wild-type (Pro12Ala) genotype, but not those with the Ala12
      variant (OR 0.86, 95%CI 0.35-2.09). Larger studies are needed to validate these
      results, which suggest that the PPARgamma Pro12Ala polymorphism may interact with
      other factors to protect against colorectal adenoma.

PMID- 15564290
TI  - A COX-2 inhibitor prevents the esophageal inflammation-metaplasia-adenocarcinoma
      sequence in rats.
AB  - Barrett's esophagus (BE) and esophageal adenocarcinoma (ADC) is associated with
      reflux of duodenal contents. Cyclooxygenase (COX)-2 is over-expressed in BE and
      ADC, and supposedly contributes to esophageal carcinogenesis. The aim of this
      study is to investigate what effect a COX-2 inhibitor has on esophageal
      adenocarcinogenesis in rats. A series of 90 rats underwent a duodenoesophageal
      reflux procedure and were divided into 2 groups. One group was given commercial
      chow (control group), and the other was given experimental chow containing
      celecoxib (celecoxib group). The animals were sacrificed sequentially, at the
      10th, 20th, 30th and, finally, 40th week after surgery, and their esophagi were
      examined. In the control group, esophagitis, columnar-lined epithelium (CLE) and
      ADC were first observed at the 10th week, 20th week and 30th week, respectively.
      Their incidences sequentially increased and at the 40th week reached 100, 89 and
      47%, respectively. In the celecoxib group, the esophagitis was mild and the
      incidence of CLE was significantly lower at each week (P < 0.001), compared with
      the control group, and ADC was not observed throughout the experiment (P < 0.05).
      COX-2 expression was observed predominantly in the stroma of inflamed esophageal
      epithelia, and up-regulated at the 10th and 20th week (P < 0.05, respectively).
      PGE2 level and proliferative activity were also up-regulated in both groups, but
      they were lower in the celecoxib group than in the control group (P < 0.05).
      Apoptosis was observed to increase with celecoxib treatment (P < 0.05). Celecoxib
      is effective in preventing CLE and ADC by suppressing esophagitis in rats.

PMID- 15564291
TI  - Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky
      coal emissions in Xuan Wei County, China.
AB  - Lung cancer mortality rates in the Xuan Wei County population are among the
      highest in China and are associated with exposure to indoor emissions from the
      burning of smoky coal. Previous studies of lung tumors from both non-smoking
      women and smoking men in this region showed high frequencies of mutations,
      consisting mostly of G-->T transversions in the p53 tumor suppressor gene and K
      ras oncogene, suggesting that these mutations were caused primarily by polycyclic
      aromatic hydrocarbons. In this study sputum samples from 92 individuals with no
      evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras
      mutations. Sputum cells were collected on glass slides by sputum
      cytocentrifugation, stained and cytopathologically analyzed. Cytologically non
      malignant epithelial cells were taken from each sputum sample using a laser
      capture microdissection microscope and molecularly analyzed. Cells taken from the
      sputum of 15 (16.3%) individuals were mutation positive, including 13 (14.1%)
      individuals each with a p53 mutation, 1 (1.1%) individual with a K-ras mutation
      and 1 (1.1%) individual with a p53 and a K-ras mutation. p53 mutations were found
      in both the sputum of individuals with evidence of chronic bronchitis (3 of 46 or
      6.5%) and those without evidence of this disease (11 of 46 or 23.9%). Therefore,
      mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent
      in non-malignant epithelial cells taken from the sputum of individuals without
      evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei
      County and were at a high risk for developing the disease.

PMID- 15564292
TI  - Prostaglandin E receptor subtype EP(1) deficiency inhibits colon cancer
      development.
AB  - Prostaglandin E(2) exerts its biological activity through binding to its membrane
      receptors, E-prostanoid (EP) receptors. Our previous finding that lack of EP(1)
      receptor inhibits the early stages of colon carcinogenesis led us to investigate
      whether EP(1) receptor deficiency reduces colon cancer development induced by
      azoxymethane (AOM) using EP(1) receptor knockout mice. At 6 weeks of age 33
      homozygous EP(1)-deficient (EP(1)(-/-)) mice and 28 wild-type (EP(1)(+/+)) mice
      were given i.p. AOM (10 mg/kg body wt) once a week for 6 weeks. At 56 weeks of
      age all animals were killed and intestinal tumors were examined. The results
      clearly indicated that lack of EP(1) receptor significantly reduced colon cancer
      incidence (27 versus 57%, P < 0.05) and multiplicity (0.30 versus 0.76, P < 0.05)
      as well as tumor volume (12.2 versus 75.6 mm(3), P < 0.05). In EP(1)(-/-) mice,
      silver stained nucleolar organization region protein count as cell proliferation
      marker was significantly reduced (1.35 versus 2.17, P < 0.001) and apoptosis was
      significantly increased (0.685 versus 0.077, P < 0.001) in colon tumors induced
      by AOM compared with those in EP(1)(+/+) mice. We confirmed that EP(1) receptor
      mRNA was overexpressed in colon cancers of EP(1)(+/+) mice using reverse
      transcription-polymerase chain reaction. These results provide strong evidence
      that the EP(1) receptor is of major importance for colon cancer development and
      it could be a new target for a mechanism-based chemoprevention strategy against
      colon cancer development.

PMID- 15564293
TI  - Validation of alternative methods of data normalization in gene co-expression
      studies.
AB  - MOTIVATION: Clusters of genes encoding proteins with related functions, or in the
      same regulatory network, often exhibit expression patterns that are correlated
      over a large number of conditions. Protein associations and gene regulatory
      networks can be modelled from expression data. We address the question of which
      of several normalization methods is optimal prior to computing the correlation of
      the expression profiles between every pair of genes. RESULTS: We use gene
      expression data from five experiments with a total of 78 hybridizations and 23
      diverse conditions. Nine methods of data normalization are explored based on all
      possible combinations of normalization techniques according to between and within
      gene and experiment variation. We compare the resulting empirical distribution of
      gene x gene correlations with the expectations and apply cross-validation to test
      the performance of each method in predicting accurate functional annotation. We
      conclude that normalization methods based on mixed-model equations are optimal.

PMID- 15564294
TI  - SpliceMachine: predicting splice sites from high-dimensional local context
      representations.
AB  - MOTIVATION: In this age of complete genome sequencing, finding the location and
      structure of genes is crucial for further molecular research. The accurate
      prediction of intron boundaries largely facilitates the correct prediction of
      gene structure in nuclear genomes. Many tools for localizing these boundaries on
      DNA sequences have been developed and are available to researchers through the
      internet. Nevertheless, these tools still make many false positive predictions.
      RESULTS: This manuscript presents a novel publicly available splice site
      prediction tool named SpliceMachine that (i) shows state-of-the-art prediction
      performance on Arabidopsis thaliana and human sequences, (ii) performs a
      computationally fast annotation and (iii) can be trained by the user on its own
      data. AVAILABILITY: Results, figures and software are available at
      http://www.bioinformatics.psb.ugent.be/supplementary_data/ CONTACT:
      sven.degroeve@psb.ugent.be; yves.vandepeer@psb.ugent.be.

PMID- 15564295
TI  - Wnt pathway curation using automated natural language processing: combining
      statistical methods with partial and full parse for knowledge extraction.
AB  - MOTIVATION: Wnt signaling is a very active area of research with highly relevant
      publications appearing at a rate of more than one per day. Building and
      maintaining databases describing signal transduction networks is a time-consuming
      and demanding task that requires careful literature analysis and extensive domain
      specific knowledge. For instance, more than 50 factors involved in Wnt signal
      transduction have been identified as of late 2003. In this work we describe a
      natural language processing (NLP) system that is able to identify references to
      biological interaction networks in free text and automatically assembles a
      protein association and interaction map. RESULTS: A 'gold standard' set of names
      and assertions was derived by manual scanning of the Wnt genes website
      (http://www.stanford.edu/~rnusse/wntwindow.html) including 53 interactions
      involved in Wnt signaling. This system was used to analyze a corpus of peer
      reviewed articles related to Wnt signaling including 3369 Pubmed and 1230 full
      text papers. Names for key Wnt-pathway associated proteins and biological
      entities are identified using a chi-squared analysis of noun phrases over
      represented in the Wnt literature as compared to the general signal transduction
      literature. Interestingly, we identified several instances where generic terms
      were used on the website when more specific terms occur in the literature, and
      one typographic error on the Wnt canonical pathway. Using the named entity list
      and performing an exhaustive assertion extraction of the corpus, 34 of the 53
      interactions in the 'gold standard' Wnt signaling set were successfully
      identified (64% recall). In addition, the automated extraction found several
      interactions involving key Wnt-related molecules which were missing or different
      from those in the canonical diagram, and these were confirmed by manual review of
      the text. These results suggest that a combination of NLP techniques for
      information extraction can form a useful first-pass tool for assisting human
      annotation and maintenance of signal pathway databases. AVAILABILITY: The
      pipeline software components are freely available on request to the authors.
      CONTACT: dstates@umich.edu SUPPLEMENTARY INFORMATION:
      http://stateslab.bioinformatics.med.umich.edu/software.html.

PMID- 15564296
TI  - A nearest-neighboring-end algorithm for genetic mapping.
AB  - MOTIVATION: High-throughput methods are beginning to make possible the genotyping
      of thousands of loci in thousands of individuals, which could be useful for
      tightly associating phenotypes to candidate loci. Current mapping algorithms
      cannot handle so many data without building hierarchies of framework maps.
      RESULTS: A version of Kruskal's minimum spanning tree algorithm can solve any
      genetic mapping problem that can be stated as marker deletion from a set of
      linkage groups. These include backcross, recombinant inbred, haploid and double
      cross recombinational populations, in addition to conventional deletion and
      radiation hybrid populations. The algorithm progressively joins linkage groups at
      increasing recombination fractions between terminal markers, and attempts to
      recognize and correct erroneous joins at peaks in recombination fraction. The
      algorithm is O (mn3) for m individuals and n markers, but the mean run time
      scales close to mn2. It is amenable to parallel processing and has recovered true
      map order in simulations of large backcross, recombinant inbred and deletion
      populations with up to 37,005 markers. Simulations were used to investigate map
      accuracy in response to population size, allelic dominance, segregation
      distortion, missing data and random typing errors. It produced accurate maps when
      marker distribution was sufficiently uniform, although segregation distortion
      could induce translocated marker orders. The algorithm was also used to map 1003
      loci in the F7 ITMI population of bread wheat, Triticum aestivum L. emend Thell.,
      where it shortened an existing standard map by 16%, but it failed to associate
      blocks of markers properly across gaps within linkage groups. This was because it
      depends upon the rankings of recombination fractions at individual markers, and
      is susceptible to sampling error, typing error and joint selection involving the
      terminal markers of nearly finished linkage groups. Therefore, the current form
      of the algorithm is useful mainly to improve local marker ordering in linkage
      groups obtained in other ways. AVAILABILITY: The source code and supplemental
      data are http://www.iubio.bio.indiana.edu/soft/molbio/qtl/flipper/ CONTACT:
      ccrane@purdue.edu.

PMID- 15564297
TI  - DSEARCH: sensitive database searching using distributed computing.
AB  - We present a distributed and fully cross-platform database search program that
      allows the user to utilize the idle clock cycles of machines to perform large
      searches using the most sensitive algorithms. For those in an academic or
      corporate environment with hundreds of idle desktop machines, DSEARCH can deliver
      a 'free' database search supercomputer. AVAILABILITY: The software is publicly
      available under the GNU general public licence from
      http://www.cs.may.ie/distributed CONTACT: tom.naughton@may.ie SUPPLEMENTARY
      INFORMATION: Full documentation and a user manual is available from
      http://www.cs.may.ie/distributed.

PMID- 15564298
TI  - Sample size for gene expression microarray experiments.
AB  - MOTIVATION: Microarray experiments often involve hundreds or thousands of genes.
      In a typical experiment, only a fraction of genes are expected to be
      differentially expressed; in addition, the measured intensities among different
      genes may be correlated. Depending on the experimental objectives, sample size
      calculations can be based on one of the three specified measures: sensitivity,
      true discovery and accuracy rates. The sample size problem is formulated as: the
      number of arrays needed in order to achieve the desired fraction of the specified
      measure at the desired family-wise power at the given type I error and
      (standardized) effect size. RESULTS: We present a general approach for estimating
      sample size under independent and equally correlated models using binomial and
      beta-binomial models, respectively. The sample sizes needed for a two-sample z
      test are computed; the computed theoretical numbers agree well with the Monte
      Carlo simulation results. But, under more general correlation structures, the
      beta-binomial model can underestimate the needed samples by about 1-5 arrays.
      CONTACT: jchen@nctr.fda.gov.

PMID- 15564299
TI  - Procom: a web-based tool to compare multiple eukaryotic proteomes.
AB  - Each organism has traits that are shared with some, but not all, organisms.
      Identification of genes needed for a particular trait can be accomplished by a
      comparative genomics approach using three or more organisms. Genes that occur in
      organisms without the trait are removed from the set of genes in common among
      organisms with the trait. To facilitate these comparisons, a web-based server,
      Procom, was developed to identify the subset of genes that may be needed for a
      trait. AVAILABILITY: The Procom program is freely available with documentation
      and examples at http://ural.wustl.edu/~billy/Procom/ CONTACT:
      billy@ural.wustl.edu.

PMID- 15564300
TI  - Evaluation of iterative alignment algorithms for multiple alignment.
AB  - MOTIVATION: Iteration has been used a number of times as an optimization method
      to produce multiple alignments, either alone or in combination with other
      methods. Iteration has a great advantage in that it is often very simple both in
      terms of coding the algorithms and the complexity of the time and memory
      requirements. In this paper, we systematically test several different iteration
      strategies by comparing the results on sets of alignment test cases. RESULTS: We
      tested three schemes where iteration is used to improve an existing alignment.
      This was found to be remarkably effective and could induce a significant
      improvement in the accuracy of alignments from most packages. For example the
      average accuracy of ClustalW was improved by over 6% on the hardest test cases.
      Iteration was found to be even more powerful when it was directly incorporated
      into a progressive alignment scheme. Here, iteration was used to improve
      subalignments at each step of progressive alignment. The beneficial effects of
      iteration come, in part, from the ability to get round the usual local minimum
      problem with progressive alignment. This ability can also be used to help reduce
      the complexity of T-Coffee, without losing accuracy. Alignments can be generated,
      using T-Coffee, to align subgroups of sequences, which can then be iteratively
      improved and merged. AVAILABILITY: All of the scripts are freely available on the
      web at http://www.bioinf.ucd.ie/people/iain/iteration.html CONTACT:
      iain.wallace@ucd.ie.

PMID- 15564301
TI  - Constructing ontology-driven protein family databases.
AB  - MOTIVATION: Protein family databases provide a central focus for scientific
      communities as well as providing useful resources to aide research. However, such
      resources require constant curation and often become outdated and discontinued.
      We have developed an ontology-driven system for capturing and managing protein
      family data that addresses the problems of maintenance and sustainability.
      RESULTS: Using protein phosphatases and ABC transporters as model protein
      families, we constructed two protein family database resources around a central
      DAML+OIL ontology. Each resource contains specialist information about each
      protein family, providing specialized domain-specific resources based on the same
      template structure. The formal structure, combined with the extraction of
      biological data using GO terms, allows for automated update strategies. Despite
      the functional differences between the two protein families, the ontology model
      was equally applicable to both, demonstrating the generic nature of the system.
      AVAILABILITY: The protein phosphatase resource, PhosphaBase, is freely available
      on the internet (http://www.bioinf.man.ac.uk/phosphabase). The DAML+OIL ontology
      for the protein phosphatases and the ABC transporters is available on request
      from the authors. CONTACT: kwolstencroft@cs.man.ac.uk.

PMID- 15564302
TI  - The ArrayExpress gene expression database: a software engineering and
      implementation perspective.
AB  - MOTIVATION: The lack of microarray data management systems and databases is still
      one of the major problems faced by many life sciences laboratories. While
      developing the public repository for microarray data ArrayExpress we had to find
      novel solutions to many non-trivial software engineering problems. Our experience
      will be both relevant and useful for most bioinformaticians involved in
      developing information systems for a wide range of high-throughput technologies.
      RESULTS: ArrayExpress has been online since February 2002, growing exponentially
      to well over 10,000 hybridizations (as of September 2004). It has been
      demonstrated that our chosen design and implementation works for databases aimed
      at storage, access and sharing of high-throughput data. AVAILABILITY: The
      ArrayExpress database is available at http://www.ebi.ac.uk/arrayexpress/. The
      software is open source. CONTACT: ugis@ebi.ac.uk.

PMID- 15564303
TI  - A fuzzy guided genetic algorithm for operon prediction.
AB  - MOTIVATION: The operon structure of the prokaryotic genome is a critical input
      for the reconstruction of regulatory networks at the whole genome level. As
      experimental methods for the detection of operons are difficult and time
      consuming, efforts are being put into developing computational methods that can
      use available biological information to predict operons. METHOD: A genetic
      algorithm is developed to evolve a starting population of putative operon maps of
      the genome into progressively better predictions. Fuzzy scoring functions based
      on multiple criteria are used for assessing the 'fitness' of the newly evolved
      operon maps and guiding their evolution. RESULTS: The algorithm organizes the
      whole genome into operons. The fuzzy guided genetic algorithm-based approach
      makes it possible to use diverse biological information like genome sequence
      data, functional annotations and conservation across multiple genomes, to guide
      the organization process. This approach does not require any prior training with
      experimental operons. The predictions from this algorithm for Escherchia coli K12
      and Bacillus subtilis are evaluated against experimentally discovered operons for
      these organisms. The accuracy of the method is evaluated using an ROC (receiver
      operating characteristic) analysis. The area under the ROC curve is around 0.9,
      which indicates excellent accuracy. CONTACT: roschen_csir@rediffmail.com.

PMID- 15564304
TI  - Accelerated off-target search algorithm for siRNA.
AB  - MOTIVATION: Designing highly effective short interfering RNA (siRNA) sequences
      with maximum target-specificity for mammalian RNA interference (RNAi) is one of
      the hottest topics in molecular biology. The relationship between siRNA sequences
      and RNAi activity has been studied extensively to establish rules for selecting
      highly effective sequences. However, there is a pressing need to compute siRNA
      sequences that minimize off-target silencing effects efficiently and to match any
      non-targeted sequences with mismatches. RESULTS: The enumeration of potential
      cross-hybridization candidates is non-trivial, because siRNA sequences are short,
      ca. 19 nt in length, and at least three mismatches with non-targets are required.
      With at least three mismatches, there are typically four or five contiguous
      matches, so that a BLAST search frequently overlooks off-target candidates. By
      contrast, existing accurate approaches are expensive to execute; thus we need to
      develop an accurate, efficient algorithm that uses seed hashing, the pigeonhole
      principle, and combinatorics to identify mismatch patterns. Tests show that our
      method can list potential cross-hybridization candidates for any siRNA sequence
      of selected human gene rapidly, outperforming traditional methods by orders of
      magnitude in terms of computational performance. AVAILABILITY:
      http://design.RNAi.jp CONTACT: yamada@cb.k.u-tokyo.ac.jp.

PMID- 15564305
TI  - Serial SimCoal: a population genetics model for data from multiple populations
      and points in time.
AB  - We present Serial SimCoal, a program that models population genetic data from
      multiple time points, as with ancient DNA data. An extension of SIMCOAL, it also
      allows simultaneous modeling of complex demographic histories, and migration
      between multiple populations. Further, we incorporate a statistical package to
      calculate relevant summary statistics, which, for the first time allows users to
      investigate the statistical power provided by, conduct hypothesis-testing with,
      and explore sample size limitations of ancient DNA data. AVAILABILITY: Source
      code and Windows/Mac executables at
      http://www.stanford.edu/group/hadlylab/ssc.html CONTACT: senka@stanford.edu.

PMID- 15564306
TI  - VitaPad: visualization tools for the analysis of pathway data.
AB  - MOTIVATION: Packages that support the creation of pathway diagrams are limited by
      their inability to be readily extended to new classes of pathway-related data.
      RESULTS: VitaPad is a cross-platform application that enables users to create and
      modify biological pathway diagrams and incorporate microarray data with them. It
      improves on existing software in the following areas: (i) It can create diagrams
      dynamically through graph layout algorithms. (ii) It is open-source and uses an
      open XML format to store data, allowing for easy extension or integration with
      other tools. (iii) It features a cutting-edge user interface with intuitive
      controls, high-resolution graphics and fully customizable appearance.
      AVAILABILITY: http://bioinformatics.med.yale.edu CONTACTS:
      matthew.holford@yale.edu; hongyu.zhao@yale.edu.

PMID- 15564307
TI  - The carbohydrate sequence markup language (CabosML): an XML description of
      carbohydrate structures.
AB  - Bioinformatics resources for glycomics are very poor as compared with those for
      genomics and proteomics. The complexity of carbohydrate sequences makes it
      difficult to define a common language to represent them, and the development of
      bioinformatics tools for glycomics has not progressed. In this study, we
      developed a carbohydrate sequence markup language (CabosML), an XML description
      of carbohydrate structures. AVAILABILITY: The language definition (XML Schema)
      and an experimental database of carbohydrate structures using an XML database
      management system are available at
      http://www.phoenix.hydra.mki.co.jp/CabosDemo.html CONTACT:
      kikuchi@hydra.mki.co.jp.

PMID- 15564308
TI  - X linked agammaglobulinaemia and rheumatoid arthritis.
AB  - BACKGROUND: Much interest has been shown recently in the pathogenic role of B
      cells in rheumatoid arthritis (RA) owing to the marked clinical responses to anti
      CD20 treatment in RA. CASE REPORT: A patient with X linked agammaglobulinaemia
      (XLA) presented with an erosive symmetric polyarthritis with histological
      features of RA, including formation of a destructive pannus. Furthermore, the
      patient developed subcutaneous nodules that were histologically indistinguishable
      from rheumatoid nodules. Surprisingly, lymphocytic infiltrates in both the
      synovium and nodule consisted almost exclusively of CD8+ T cells. DISCUSSION:
      Although some peculiar B cell subsets have been described in patients with XLA,
      no B cell subsets could be demonstrated in synovial tissue or the subcutaneous
      nodule. This case illustrates that classical RA can develop in the absence of
      mature B cells.

PMID- 15564309
TI  - Infliximab treatment in ankylosing spondylitis: an observational study.
AB  - OBJECTIVE: To investigate efficacy, toxicity, and drug discontinuation in
      patients with ankylosing spondylitis (AS) treated with infliximab. METHODS: 35
      patients with AS with mean (SD) age 42.5 (12.6) years and mean (SD) disease
      duration 14.5 (8.0) years were studied for 2 years. Patients entering the study
      had a negative tuberculin skin test, were fully informed about the treatment, and
      were followed up regularly. Infliximab, 5 mg/kg weight, was given intravenously
      at weeks 0, 2, 6, and every 8 weeks thereafter. Data concerning infliximab
      tolerability, adverse events, interval, and drug discontinuation were all
      recorded. Clinical improvement according to the BASDAI and the Ankylosing
      Spondylitis Assessment Study group (ASAS) 20%, 40%, and ASAS 5/6 response
      criteria were recorded. RESULTS: After 1 year, 20 (57%) patients achieved the
      BASDAI 50% response criteria, 25 (71%) achieved ASAS 20%, 23 (66%) reached ASAS
      40%, and 18 (51%) attained ASAS 5/6. After 2 years' treatment, 11 (31%) patients
      achieved BASDAI 50% response criteria, 14 (40%) ASAS 20%, 11 (31%) ASAS 40%, and
      9 (26%) ASAS 5/6. Clinical improvement was associated with an improved BASFI and
      reduction of CRP. After 2 years' treatment, "infliximab survival" was 89%.
      Treatment was well tolerated and adverse events were mild; 3 patients
      discontinued the study. CONCLUSION: Infliximab was effective, safe, and well
      tolerated in patients with AS.

PMID- 15564310
TI  - Soluble TRAIL concentrations are raised in patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: Increased apoptosis may induce autoimmune conditions. Apoptosis is
      induced by binding of death receptor ligands, members of the tumour necrosis
      factor (TNF) superfamily, to their cognate receptors. The Fas-Fas ligand pathway
      has been studied extensively in relation to systemic lupus erythematosus (SLE).
      However, other death pathways are also considered important. TNF related
      apoptosis inducing ligand (TRAIL), another ligand of the TNF superfamily, induces
      apoptosis in sensitive cells. OBJECTIVE: To assess soluble (s) TRAIL
      concentrations in sera of SLE patients. METHODS: 40 SLE patients were studied (20
      with active and 20 with inactive disease). Serum sTRAIL concentrations were
      measured by a solid phase sandwich enzyme linked immunosorbent assay. Levels in
      SLE patients were compared with those in patients with rheumatoid arthritis (n =
      20), Wegener's granulomatosis (n = 20), and healthy controls (n = 20). RESULTS:
      Mean (SEM) serum sTRAIL concentration in SLE patients (936.0 (108.2) pg/ml) was
      higher than in healthy controls (509.4 (33.8) pg/ml; p<0.01) or in disease
      control patients with rheumatoid arthritis (443.8 (36.1) pg/ml, p<0.001) or
      Wegener's granulomatosis (357.1 (32.2) pg/ml; p<0.001). The mean serum sTRAIL
      concentration was 1010.2 (168.0) pg/ml for patients with inactive disease and
      861.8 (138.7) pg/ml for those with active disease. sTRAIL values were not
      correlated with specific manifestations of the disease, such as leucopenia or
      lymphopenia, or with SLE disease activity index. CONCLUSIONS: Serum sTRAIL
      concentrations are increased SLE patients. This seems to be disease specific and
      could indicate a role for TRAIL in SLE pathophysiology.

PMID- 15564311
TI  - Evaluation of WOMAC 20, 50, 70 response criteria in patients treated with hylan G
      F 20 for knee osteoarthritis.
AB  - OBJECTIVE: A secondary analysis of a previously conducted one year randomised
      controlled trial to evaluate the capacity of responder criteria based on the
      WOMAC index to detect between treatment group differences. METHODS: 255 patients
      with knee osteoarthritis were randomised to "appropriate care with hylan G-F 20"
      (AC+H) or "appropriate care without hylan G-F 20" (AC). In the original analysis,
      two definitions of patient response from baseline to month 12 were used: (1) at
      least a 20% reduction in WOMAC pain score (WOMAC 20P); (2) at least a 20%
      reduction in WOMAC pain score and at least a 20% reduction in either WOMAC
      function or stiffness score (WOMAC 20PFS). For this analysis, a responder was
      identified using 50% and 70% minimum clinically important response levels to
      investigate how increasing response affects the ability to detect treatment group
      differences. RESULTS: The hylan G-F 20 group had numerically more responders
      using all patient responder criteria. Increasing the response level from 20% to
      50% detected similar differences between treatment groups (25% to 29%).
      Increasing the response level to 70% reduced the differences between treatment
      groups (11% to 12%) to a point where the differences were not significant after
      Bonferroni adjustment. CONCLUSIONS: These results provide evidence for
      incorporating response levels (WOMAC 50) in clinical trials. While differences at
      the highest threshold (WOMAC 70) were not statistically detectable, an
      appropriately powered study may be capable of detecting differences even at this
      very high level of improvement.

PMID- 15564312
TI  - A late-transition metal oxo complex: K7Na9[O=PtIV(H2O)L2], L = [PW9O34]9-.
AB  - Terminal mono-oxo complexes of the late transition metal elements have long been
      considered too unstable to synthesize because of repulsion between the oxygen
      electrons and the mostly filled metal d orbitals. A platinum(IV)-oxo compound
      flanked by two polytungstate ligands, K7Na9[O=Pt(H2O)L2], L = [PW9O34(9-)], has
      now been prepared and isolated at room temperature as air-stable brown crystals.
      X-ray and neutron diffraction at 30 kelvin revealed a very short [1.720(18)
      angstrom] Pt-O bond and no evidence of a hydrogen atom at the terminal oxygen,
      ruling out a better precedented Pt-OH complex. Density functional theory and
      spectroscopic data account for the stability of the Pt(IV)-oxo unit by electron
      withdrawal into delocalized orbitals of the polytungstates.

PMID- 15564313
TI  - Electron coherence in a melting lead monolayer.
AB  - We used angle-resolved photoemission spectroscopy to measure the electronic
      dispersion and single-particle spectral function in a liquid metal. A lead
      monolayer supported on a copper (111) surface was investigated as the temperature
      was raised through the melting transition of the film. Electron spectra and
      momentum distribution maps of the liquid film revealed three key features of the
      electronic structure of liquids: the persistence of a Fermi surface, the filling
      of band gaps, and the localization of the wave functions upon melting. Distinct
      coherence lengths for different sheets of the Fermi surface were found,
      indicating a strong dependence of the localization lengths on the character of
      the constituent atomic wave functions.

PMID- 15564314
TI  - Epithelial-to-mesenchymal transition generates proliferative human islet
      precursor cells.
AB  - Insulin-expressing beta cells, found in pancreatic islets, are capable of
      generating more beta cells even in the adult. We show that fibroblast-like cells
      derived from adult human islets donated postmortem proliferate readily in vitro.
      These mesenchymal-type cells, which exhibit no hormone expression, can then be
      induced to differentiate into hormone-expressing islet-like cell aggregates,
      which reestablishes the epithelial character typical of islet cells.
      Immunohistochemistry, in situ hybridization, and messenger RNA measurements in
      single cells and cell populations establish the transition of epithelial cells
      within islets to mesenchymal cells in culture and then to insulin-expressing
      epithelial cells.

PMID- 15564315
TI  - Different inhibitory effects in the early and late phase of treatment with KAT
      681, a liver-selective thyromimetic, on rat hepatocarcinogenesis induced by 2
      acetylaminofluorene and partial hepatectomy after diethylnitrosamine initiation.
AB  - We recently reported that short-term treatment with KAT-681 (KAT), a liver
      selective thyromimetic, inhibits the development of preneoplastic lesions in rat
      livers and may be a candidate chemopreventive agent for hepatocarcinogenesis. In
      this study, time-course observations of hepatocellular proliferative lesions were
      carried out during short-term and long-term treatment with KAT to investigate its
      anti-hepatocarcinogenic effects. The hepatocellular proliferative lesions in male
      F344 rats were induced by the initiation treatment of diethylnitrosamine (DEN),
      followed by treatment with 2-acetylaminofluorene (2-AAF) and partial hepatectomy
      (PH). The rats were administered KAT orally at a dose of 0.25 mg/kg/day for 3
      weeks (experiment 1) or 0.1 mg/kg/day for 20 weeks (experiment 2). In experiment
      1, a serial reduction in the number of altered hepatocellular foci (AHF) with
      positive expression of glutathione S-transferase placental form (GST-P) was
      observed until day 14 of the treatment period. The proliferative index (PI) of
      hepatocytes in the AHF significantly increased in the KAT group throughout the
      treatment period, with a peak on day 2. KAT treatment showed no obvious effects
      on GST-P-positive hepatocellular adenomas (HCAs) at any time point. In contrast,
      long-term KAT treatment in experiment 2 revealed a reduction in the mean size of
      HCAs in addition to reductions in the number and mean size of AHF. The PIs within
      the lesions in KAT-treated rats were significantly lower than those in controls.
      The present study indicates that KAT has different inhibitory effects on
      hepatocarcinogenesis in the early and late phases of KAT treatment; there is a
      reduction in AHF with enhanced cell proliferation in the early phase and the
      inhibition of development of AHF and HCAs with suppression of cell proliferation
      in the late phase. These results may suggest further potential of KAT as a
      promising chemopreventive agent for hepatocarcinogenesis.

PMID- 15564316
TI  - Carcinogenic activity of cigarette smoke gas phase and its modulation by beta
      carotene and N-acetylcysteine.
AB  - Male strain A/J mice were exposed for six hours a day, five days a week for six
      months to either full tobacco smoke or to tobacco smoke drawn through a HEPA
      filter that removed more than 99% of particulate matter. After another four
      months in air, the animals were sacrificed and lung tumors were counted for
      calculation of multiplicities and incidences. Analysis of the chamber atmospheres
      showed that in the filtered smoke the concentrations of polycyclic aromatic
      hydrocarbons and tobacco smoke specific nitrosamines were reduced to from below
      18% to even nondetectable levels of the original values measured in the
      unfiltered smoke. Aldehydes and other volatile organic compounds such as 1,3
      butadiene, benzene, or acrolein were reduced to about 50 to 90% of the
      concentrations found in unfiltered smoke. Some potentially carcinogenic metals
      reached levels in filtered smoke ranging from 77% to less than 1% found in full
      smoke. The mice exposed to the filtered smoke atmosphere had practically
      identical lung tumor multiplicities and incidence as had the animals exposed to
      full smoke, significantly higher than in air exposed controls. Diets containing
      0.5% beta-carotene or 0.4% N-acetylcysteine afforded some chemoprevention. It was
      tentatively concluded that 1,3-butadiene might be an important contributor to
      lung tumorigenesis in this mouse model of tobacco smoke carcinogenesis.

PMID- 15564317
TI  - Mode of mutagenic action for the biocide Bioban CS-1246 in mouse lymphoma cells
      and implications for its in vivo mutagenic potential.
AB  - The biocidal agent, BIOBAN CS-1246 (7-ethyl bicyclooxazolidine, CAS# 7747-35-5,
      CS-1246) induced a concentration-dependent mutagenic response in mouse lymphoma
      (L5178Y TK+/-) cells both with and without the addition of S9 metabolic
      activation. Previous data indicating the ability of CS-1246 to hydrolyze in
      aqueous media to generate formaldehyde (FA), led us to investigate the potential
      role of FA in the CS-1246-induced mutagenic response in the mouse lymphoma assay
      (MLA). To accomplish this, the MLA on CS-1246 was repeated in the presence of a
      metabolizing system (formaldehyde dehydrogenase/NAD+), which was shown to
      successfully inhibit the mutagenic response of formaldehyde in this assay system.
      Significantly, the observed mutagenicity of CS-1246 was completely abrogated when
      the cultures were supplemented with formaldehyde dehydrogenase/NAD+, suggesting
      that the positive MLA response was attributable to the generation of FA in situ.
      These results demonstrate that in vitro mutagenicity of CS-1246 in the MLA is
      most likely associated with FA. Negative results from two in vivo assays for
      genotoxicity were consistent with the known activity of FA in these assays. In
      the mouse bone marrow micronucleus (MNT), there were no significant increases in
      micronucleated polychromatic erythrocytes (with evaluation of 2000/animal), after
      treatment with 0.5, 1, and 2 g/kg/day CS-1246 (6/dose group) for 2 consecutive
      days and sacrifice 24 h later. Furthermore, in the unscheduled DNA synthesis
      (UDS) study, male F344 rats (5 /dose group), given a single oral gavage (0, 1,
      and 2 g/kg) and evaluated at two time points (2-4 and 14-15 h post dosing), did
      not elicit an UDS response, indicating a lack of DNA reactivity in vivo. Based on
      the negative in vivo findings, it can be inferred that the FA detoxification
      mechanisms that exist in intact organisms prevent the likelihood of generating FA
      at levels capable of causing genotoxicity following exposure to CS-1246 at low,
      environmentally relevant concentrations. The extensive literature on FA would
      therefore be of value in assessing the carcinogenic risk to humans and animals
      from CS-1246 exposure.

PMID- 15564318
TI  - Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick
      embryo heart chronotropic response to isoproterenol but not to agents affecting
      signals downstream of the beta-adrenergic receptor.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in
      laboratory animals, including alteration in several processes in which beta
      adrenergic receptor (beta-AR) signaling plays important roles. Thus, our
      laboratory investigated the effects of TCDD on beta-AR expression and signal
      transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or
      0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was
      assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias
      and decreased the positive chronotropic responsiveness of the heart to
      isoproterenol. The reduced beta-AR responsiveness was, in part, independent of
      any overt morphological changes in the heart as chick embryos exposed to TCDD on
      D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of
      the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD
      did not decrease the chronotropic response of the heart to agents that stimulate
      signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more
      sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5
      beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above
      baseline. TCDD exposure also augmented the negative chronotropic response of the
      heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus
      control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac
      beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure
      to TCDD on D0. These findings establish that a functional end point of the
      developing chick heart is sensitive to TCDD exposure and that the TCDD-induced
      reduction in beta-AR responsiveness may result from alterations in signal
      transduction upstream of adenylyl cyclase.

PMID- 15564319
TI  - Biocytin filling of adult gonadotropin-releasing hormone neurons in situ reveals
      extensive, spiny, dendritic processes.
AB  - Ultrastructural studies suggest that GnRH neurons receive relatively few synaptic
      inputs. However, these techniques are biased toward the analysis of portions of
      the neuron containing GnRH peptide. Using acute brain slices prepared from
      transgenic GnRH-green fluorescent protein mice, individual fluorescing GnRH
      neurons were identified, patched, and filled with the small-molecular-weight dye
      biocytin. Cells were subsequently visualized with an avidin-conjugated
      fluorophore, and their morphological characteristics were analyzed by confocal
      microscopy. In total, 45 GnRH neurons from seven adult male and eight diestrus
      female mice were examined. Unexpectedly, we found that GnRH neurons possess
      remarkably long dendritic processes, in some cases extending over 1000 microm
      distal to the cell body. The somata and dendrites of all GnRH neurons were
      decorated with an assortment of spine-like protrusions, including filopodia, in
      an heterogeneous manner. Overall, GnRH neurons had a mean dendritic spine density
      of 0.4 spines/microm, with the highest densities found in the first 50 microm of
      the dendrite. GnRH neurons with dendrites running in a horizontal orientation had
      significantly (P < 0.05) more spines than dendrites with a vertical orientation.
      The comparison of male and female GnRH neurons revealed no sexually
      differentiated characteristics of somal or dendritic spine density. Using a
      technique in which the full extent of the GnRH neuron can be visualized, we
      demonstrate here a previously unrecognized GnRH neuron morphology of long
      dendrites covered in spines. These observations suggest that GnRH neurons are not
      poorly innervated and that they receive abundant excitatory synaptic inputs.

PMID- 15564320
TI  - Role of the constitutive androstane receptor in xenobiotic-induced thyroid
      hormone metabolism.
AB  - The induction of hepatic drug metabolizing enzymes alters not only the metabolism
      of the xenobiotic substances that induce them but also the metabolism of various
      endogenous hormones. The xenobiotic receptor constitutive androstane receptor
      (CAR) (NR1I3) mediates the well-studied induction of CYP2B genes and other drug
      metabolizing enzymes by phenobarbital (PB), an antiepileptic drug that has been
      shown to alter thyroid hormone (TH) levels. Here we show that CAR is required for
      PB-mediated disruption of TH homeostasis and the induction of thyroid follicular
      cell proliferation. Treatment with PB or the more potent and more effective CAR
      ligand 1, 4-bis-[2-(3, 5,-dichloropyridyloxy)] benzene resulted in universal
      induction of thyroid hormone glucuronidation and sulfation pathways in a CAR
      dependent manner. This resulted in a decrease in serum T4 concentration and a
      concomitant increase in serum TSH levels. CAR activation also decreased serum T3
      levels in mice in which T3 production was blocked. The increase in serum TSH
      levels resulted in the stimulation of thyroid-follicular cell proliferation.
      These results highlight the central role of the xenosensor CAR in drug-hormone
      interactions.

PMID- 15564321
TI  - Intrauterine growth restriction in humans is associated with abnormalities in
      placental insulin-like growth factor signaling.
AB  - The IGFs promote the growth and development of the feto-placental unit during
      gestation, and impairment of their placental actions may result in altered
      intrauterine growth of the fetus. In this study, proteins involved in IGF
      signaling were investigated in human placentas from pregnancies complicated by
      intrauterine growth restriction (IUGR) compared with those from normal
      pregnancies. IUGR placentas exhibited 33% reduction in the protein content of IGF
      I receptors, but no changes in insulin receptor protein levels. In addition,
      insulin receptor substrate-2 (IRS-2) protein levels were reduced in IUGR
      placentas, with no changes in IRS-1 or Shc protein content, and this was
      associated with a parallel decrease in IRS-2-associated phosphatidyl inositol 3
      kinase. Akt protein expression was also reduced in IUGR, whereas phosphorylation
      of Akt and its substrate glycogen synthase kinase-3 was unchanged. Finally, in
      IUGR placentas there was impaired activation of multiple members of the MAPK
      family, because phosphorylation of p38 and c-Jun N-terminal kinase was reduced
      70%. In conclusion, human placentas from pregnancies complicated by IUGR are
      characterized by decreased IGF-I receptor content, selective impairment of the
      IRS-2/ phosphatidyl inositol 3-kinase pathway, and reduced p38 and c-Jun N
      terminal kinase activation. The observed abnormalities in IGF-I signaling may
      contribute to altered fetal growth and development in human IUGR.

PMID- 15564322
TI  - The putative tumor suppressor deleted in malignant brain tumors 1 is an estrogen
      regulated gene in rodent and primate endometrial epithelium.
AB  - Deleted in malignant brain tumors 1 (DMBT1) is a candidate suppressor of
      malignancies of the brain, lung, gut, and breast. We have been studying gene
      expression in the uterus in the presence of estrogens and their antagonists.
      Here, we show that DMBT1 RNA levels are robustly increased by estrogen treatment
      in the uteri of ovariectomized monkeys and rats. In monkeys, the progestin
      antagonist mifepristone inhibits estrogen-dependent uterine proliferation. As
      determined by a microarray experiment and quantitative analysis of RNA levels,
      mifepristone inhibited estrogenic induction of DMBT1. DMBT1 was not expressed in
      intact monkeys that were treated with a gonadotropin agonist to suppress
      steroidogenesis. An in vitro transfection study with human DMBT1 promoter
      constructs showed that an Alu site approximately 3000 nucleotides upstream of the
      gene mediates estrogenic regulation. Surprisingly, the estrogen antagonists
      tamoxifen, raloxifene, and ICI 182,780 also induced gene expression via this Alu
      site. Rodents represent a more convenient model system for studying uterine
      biology than monkeys. In rats, uterine DMBT1 RNA levels were dramatically up
      regulated by estrogen. Consistent with the transfection study, tamoxifen and
      raloxifene increased DMBT1 RNA levels in vivo, but ICI 182,780 inhibited an
      estrogen-induced increase. Immunohistochemical studies showed that DMBT1 is
      specifically induced in glandular and luminal epithelia of the rat endometrium.
      Our experiments establish that DMBT1 is an estrogen-responsive gene with a
      possible role in endometrial proliferation or differentiation, and they have
      implications for the putative tumor suppressive and mucosal protective functions
      of DMBT1 in the uterus.

PMID- 15564323
TI  - Fibroblast growth factor receptors as molecular targets in thyroid carcinoma.
AB  - Several molecular abnormalities of potential therapeutic target value have been
      described in thyroid neoplastic transition. We report the expression of the
      fibroblast growth factor receptor family (FGFR-1-4) in normal thyroid tissues,
      human thyroid cancers of various types and behaviors, and cell lines
      representative of the spectrum of differentiation of tumors derived from
      follicular epithelial cells. FGFR-2 was the only receptor consistently detected
      in normal human thyroid tissue, and its expression diminished in all thyroid
      cancers and carcinoma cell lines, suggesting that it may have a protective role.
      FGFR-1 and FGFR-3 were expressed in most well-differentiated tumor types. FGFR-4,
      however, was expressed predominantly in aggressive tumor types and the most
      rapidly proliferative cell lines, indicating that it may promote the progression
      of these tumors. To specifically determine the function of FGFR-4 in thyroid
      carcinoma, gain- or loss-of-function studies were performed in cell lines
      representative of the spectrum of thyroid cancer behavior. Introduction of FGFR-4
      resulted in enhanced cell proliferation, an effect that was more pronounced in
      cell lines derived from aggressive tumors than in those derived from more
      indolent neoplasms. Moreover, transduction of a dominant-negative FGFR attenuated
      cell proliferation in the aggressive poorly differentiated cell lines with no
      appreciable effect in well-differentiated cells. Pharmacologic FGFR-4 tyrosine
      kinase inhibition resulted in significant proliferation arrest in an aggressive
      cell line endogenously expressing the receptor. Furthermore, systemic
      administration of the FGFR tyrosine kinase inhibitor PD173074 resulted in
      significant inhibition of follicular thyroid carcinoma-derived cell growth in
      xenografted severe combined immunodeficient mice. These data indicate a role for
      FGFR-4 in human thyroid cancer cell progression and provide a rationale for FGFR
      manipulation as a potentially novel therapeutic approach.

PMID- 15564324
TI  - Increased neurogenesis in dentate gyrus of long-lived Ames dwarf mice.
AB  - Neurogenesis occurs throughout adult life in the dentate gyrus of mammalian
      hippocampus and has been suggested to play an important role in cognitive
      function. Multiple trophic factors including IGF-I have been demonstrated to
      regulate hippocampal neurogenesis. Ames dwarf mice live considerably longer than
      normal animals and maintain physiological function at youthful levels, including
      cognitive function, despite a deficiency of circulating GH and IGF-I. Here we
      show an increase in numbers of newly generated cells [bromodeoxyuridine (BrdU)
      positive] and newborn neurons (neuronal nuclear antigen and BrdU positive) in the
      dentate gyrus of adult dwarf mice compared with normal mice using BrdU labeling.
      Despite the profound suppression of hippocampal GH expression, hippocampal IGF-I
      protein levels are up-regulated and the corresponding mRNAs are as high in Ames
      dwarf as in normal mice. Our results suggest that local/hippocampal IGF-I
      expression may have induced the increase in hippocampal neurogenesis, and
      increased neurogenesis might contribute to the maintenance of youthful levels of
      cognitive function during aging in these long-lived animals.

PMID- 15564325
TI  - Partial reversibility of growth hormone (GH) deficiency in the GH-releasing
      hormone (GHRH) knockout mouse by postnatal treatment with a GHRH analog.
AB  - The proliferation of pituitary somatotroph cells and the synthesis and secretion
      of GH require the hypothalamic peptide GH-releasing hormone (GHRH). Accordingly,
      we have shown that mice with targeted disruption [knockout (KO)] of the GHRH gene
      (GHRHKO) have isolated GH deficiency (GHD) and anterior pituitary hypoplasia. The
      weight of GRHRKO mice is about 60% that of normal mice by 12 wk of age. The
      phenotype is strikingly similar to that observed in the mouse with mutated GHRH
      receptor (little). It is not known whether exposure to endogenous GHRH during
      intrauterine growth is necessary for postnatal GH secretion, and whether GHD due
      to congenital lack of GHRH activity would be reversible by treatment with GHRH
      during the postnatal period. To answer this question, we treated GHRHKO mice with
      a long-acting superactive GHRH analog (JI-38) at two ages: from wk 2-6 (2 microg,
      twice a day) and from wk 12-16 (4 microg, twice a day). Normal littermates served
      as controls. At both ages JI-38 caused growth acceleration, increase in size of
      the pituitary gland, increase in pituitary GH mRNA and GH protein levels and
      serum GH, and significant increase in liver IGF-I mRNA, although none of these
      parameters was fully normalized. Our findings demonstrate that GHD and pituitary
      hypoplasia in GHRHKO mice may be partially reversed by long-term treatment with a
      GHRH analog, and that somatotroph cells maintain responsiveness to GHRH even if
      this factor is absent during intrauterine development.

PMID- 15564326
TI  - Effects of changing gonadotropin-releasing hormone pulse frequency and estrogen
      treatment on levels of estradiol receptor-alpha and induction of Fos and
      phosphorylated cyclic adenosine monophosphate response element binding protein in
      pituitary gonadotropes: studies in hypothalamo-pituitary disconnected ewes.
AB  - Estrogen receptor-alpha (ER alpha) levels in gonadotropes are increased during
      the follicular phase of the ovine estrous cycle, a time of increased frequency of
      pulsatile secretion of GnRH and elevated plasma estrogen levels. In the present
      study, our first aim was to determine which of these factors causes the rise in
      the number of gonadotropes with ER alpha. Ovariectomized hypothalamo-pituitary
      disconnected ewes (n = 4-6) received the following treatments: 1) no treatment,
      2) injection (im) of 50 microg estradiol benzoate (EB), 3) pulses (300 ng iv) of
      GnRH every 3 h, 4) GnRH treatment as in group 3 and EB treatment as in group 2,
      5) increased frequency of GnRH pulses commencing 20 h before termination, and 6)
      GnRH treatment as in group 5 with EB treatment. These treatments had predictable
      effects on plasma LH levels. The number of gonadotropes in which ER alpha was
      present (by immunohistochemistry) was increased by either GnRH treatment or EB
      injection, but combined treatment had the greatest effect. Immunohistochemistry
      was also performed to detect phosphorylated cAMP response element binding protein
      (pCREB) and Fos protein in gonadotropes. The number of gonadotropes with Fos and
      with pCREB was increased only in group 6. We conclude that either estrogen or
      GnRH can up-regulate ER alpha in pituitary gonadotropes. On the other hand,
      during the period of positive feedback action of estrogen, the appearance of
      pCREB and Fos in gonadotropes requires the combined action of estrogen and
      increased frequency of GnRH input. This suggests convergence of signaling for
      GnRH and estrogen.

PMID- 15564327
TI  - Regulation of carbohydrate metabolism by the farnesoid X receptor.
AB  - The farnesoid X receptor (FXR; NR1H4) is a nuclear hormone receptor that
      functions as the bile acid receptor. In addition to the critical role FXR plays
      in bile acid metabolism and transport, it regulates a variety of genes important
      in lipoprotein metabolism. We demonstrate that FXR also plays a role in
      carbohydrate metabolism via regulation of phosphoenolpyruvate carboxykinase
      (PEPCK) gene expression. Treatment of either H4IIE or MH1C1 rat hepatoma cell
      lines as well as primary rat or human hepatocytes with FXR agonists led to
      stimulation of PEPCK mRNA expression to levels comparable to those obtained with
      glucocorticoid receptor agonists. We examined the physiological significance of
      FXR agonist-induced enhancement of PEPCK expression in primary rat hepatocytes.
      In addition to inducing PEPCK expression in primary hepatocytes, FXR agonists
      stimulated glucose output to levels comparable to those observed with a
      glucocorticoid receptor agonist. Consistent with these observations, treatment of
      C57BL6 mice with GW4064 significantly increased hepatic PEPCK expression.
      Activation of FXR initiated a cascade involving induction of peroxisome
      proliferator-activated receptor alpha and TRB3 expression that is consistent with
      stimulation of PEPCK gene expression via interference with a pathway that may
      involve Akt-dependent phosphorylation of Forkhead/winged helix transcription
      factor (FOXO1). The FXR-peroxisome proliferator-activated receptor alpha-TRB3
      pathway was conserved in rat hepatoma cell lines, mice, as well as primary human
      hepatocytes. Thus, in addition to its role in the regulation of lipid metabolism,
      FXR regulates carbohydrate metabolism.

PMID- 15564328
TI  - Ghrelin is produced by the human erythroleukemic HEL cell line and involved in an
      autocrine pathway leading to cell proliferation.
AB  - Ghrelin, a ligand of the GH secretagogue receptor (GHS-R 1a), is a 28-amino acid
      peptide with an unusual octanoyl group on Ser3, crucial for its biological
      activity. For the first time, ghrelin and GHS-R 1b, a truncated variant of the
      receptor resulting from alternative splicing, but not GHS-R 1a, mRNAs were
      detected in the human erythroleukemic cell line HEL. Two antibodies, used for
      RIA, were directed against octanoylated and total (octanoylated and
      desoctanoylated) ghrelin, and the recognized epitopes were characterized. Using
      reverse phase HPLC analysis followed by RIA, we demonstrated that octanoylated
      and desoctanoylated ghrelins were present in HEL cells and their culture medium,
      of which more than 90% was octanoylated. The ghrelin levels were not affected
      after 24 h treatment with sodium butyrate, phorbol 12-myristate 13-acetate, or
      forskolin, but a significant 3-fold increase in desoctanoylated ghrelin was
      detected in the culture medium after 48 h treatment with sodium butyrate. The
      antighrelin SB801 and SB969 antisera inhibited HEL cell proliferation by 24% and
      39%, respectively, after 72 h. Taken together, these data suggested that
      endogenous ghrelin stimulated HEL cell proliferation by an autocrine pathway
      involving an unidentified receptor, distinct from GHS-R1a, and that the HEL cell
      line represents a unique model to study the octanoylation of ghrelin.

PMID- 15564329
TI  - Lipopolysaccharide directly stimulates cortisol secretion by human adrenal cells
      by a cyclooxygenase-dependent mechanism.
AB  - Activation of the hypothalamo-pituitary-adrenal axis by bacterial
      lipopolysaccharide (LPS; endotoxin) is well documented, although there has been
      uncertainty about whether LPS exerts a direct effect at the level of the adrenal.
      The present study found that LPS caused a dose-dependent stimulation of basal
      cortisol secretion by the human adrenocortical cell line, NCI-H295R, without
      affecting aldosterone. The expression of both Toll-like receptor 2 (TLR2) and
      TLR4 was demonstrated in these cells, and the specific ligands for TLR4 (purified
      LPS and lipid A) and TLR2 (Pam3Cys) were found to stimulate cortisol release,
      suggesting that these receptors may mediate the effects of LPS in adrenal cells,
      as has been shown in other cell types. LPS was also found to stimulate
      prostaglandin E2 release by these cells. The effects of LPS on cortisol were
      attenuated in the presence of both indomethacin and a specific COX-2 inhibitor,
      but not a COX-1 inhibitor, suggesting an obligatory role for COX-2 activation and
      prostaglandin synthesis in the adrenal response to LPS.

PMID- 15564330
TI  - Effects of polypeptide YY(3-36) upon luteinizing hormone-releasing hormone and
      gonadotropin secretion in prepubertal rats: in vivo and in vitro studies.
AB  - Polypeptide YY(3-36) (PYY(3-36)) is a gastrointestinal secreted molecule, agonist
      of neuropeptide Y (NPY) receptor subtypes Y2 and Y5, recently involved in the
      control of food intake. Notably, several factors with key roles in energy
      homeostasis conduct pleiotropic effects upon the reproductive axis. However,
      whether PYY(3-36) is provided with similar biological actions remains so far
      largely unexplored. To address this issue, expression analyses of neuropeptide Y
      receptor Y2 and Y5 genes were conducted at the pituitary and the hypothalamus,
      and functional studies testing the effects of PYY(3-36) in vivo and in vitro were
      implemented, using the prepubertal rat as a model. Expression of the genes
      encoding Y2 and Y5 receptors was demonstrated, albeit at low levels, in whole
      hypothalamic and pituitary samples, and challenge of pituitary tissue with
      increasing doses of PYY(3-36) elicited LH and FSH secretion in male and female
      rats, a response that was persistently observed in the absence of extracellular
      calcium. Moreover, 10(-6) m PYY(3-36) enhanced LH and FSH responsiveness to LHRH
      in vitro. In contrast, systemic ip administration of PYY(3-36) over a range of
      doses (3, 10, and 30 microg/kg) failed to significantly modify serum LH levels in
      males and females, whereas central (intracerebroventricular) injection of 3 nmol
      PYY(3-36) inhibited LH secretion in vivo, and 10(-6) m PYY(3-36) decreased LHRH
      release by hypothalamic fragments in vitro in male but not in female rats.
      Overall, our data document the complex mode of action of the gut-derived
      anorexigenic signal PYY(3-36) at the hypothalamic-pituitary unit in the control
      of gonadotropin secretion and evidence that, as is the case for other peripheral
      factors with key roles in energy balance (as leptin and ghrelin), PYY(3-36) might
      play a role in the neuroendocrine modulation of the reproductive axis.

PMID- 15564331
TI  - Defective glucose-stimulated insulin release in the diabetic Goto-Kakizaki (GK)
      rat coincides with reduced activity of the islet carbon monoxide signaling
      pathway.
AB  - The Goto-Kakizaki (GK) rat displays a markedly reduced insulin response to
      glucose, a defect that is thought to be coupled to an impaired glucose signaling
      in the beta-cell. We have examined whether carbon monoxide (CO), derived from
      beta-cell heme oxygenase (HO), might be involved in the secretory dysfunction.
      Immunocytochemical labeling of constitutive HO (HO-2) showed no overt difference
      in fluorescence pattern in islets from GK vs. Wistar controls. However, isolated
      islets from GK rats displayed a markedly impaired HO activity measured as CO
      production (-50%), and immunoblotting revealed an approximately 50% reduction of
      HO-2 protein expression compared with Wistar controls. Furthermore, there was a
      prominent expression of inducible HO (HO-1) in GK islets. Incubation of isolated
      islets showed that the glucose-stimulated CO production and the glucose
      stimulated insulin response were considerably reduced in GK islets compared with
      Wistar islets. Addition of the HO activator hemin or gaseous CO to the incubation
      media brought about a similar amplification of glucose-stimulated insulin release
      in GK and Wistar islets, suggesting that distal steps in the HO-CO signaling
      pathway were not appreciably affected. We conclude that the defective insulin
      response to glucose in the GK rat can be explained, at least in part, by a marked
      impairment of the glucose-HO-CO signaling pathway as manifested by a prominent
      decrease in glucose stimulation of islet CO production and a reduced expression
      of HO-2. A possible role of HO-1 expression as a compensatory mechanism in the GK
      islets is presently unclear.

PMID- 15564332
TI  - Gonadotropin-releasing hormone induction of apoptosis in the testes of goldfish
      (Carassius auratus).
AB  - Apoptosis, or programmed cell death, can occur via death receptor or
      mitochondrial pathways. Normal spermatogenesis in mammals involves apoptosis
      mediated, in part, by the death receptor fas and its ligand. The regulation of
      programmed cell death in the gonads has been shown to be dependent on a number of
      locally produced factors, including GnRH. Whereas the role of GnRH in the control
      of apoptosis and follicular atresia has been documented in the mammalian ovary,
      GnRH regulation of testicular apoptosis remains obscure. A previous study in our
      laboratory demonstrated the involvement of GnRH on the induction of DNA
      fragmentation in mature, perispawning testis. In this study, we tested the
      hypothesis that GnRH plays a differential regulatory role during male gamete
      maturation by studying the effect of GnRH on the induction of apoptosis during
      goldfish spermatogenesis. Treatment with GnRH resulted in DNA fragmentation only
      during late stages of spermatogenesis as assessed by oligonucleotide detection
      and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick
      end labeling assays. The GnRH-induced apoptosis in the goldfish testis was found
      to be mediated by increased levels of fas and fas ligand-like proteins as well as
      elevated activity of caspase-3 (an executioner caspase) and -8 (a death receptor
      activated caspase). The results suggest the involvement of the death receptor
      pathway in GnRH-induced apoptosis, providing support for the hypothesis that GnRH
      plays an important role in the control of spermatogenesis in the goldfish testis.

PMID- 15564333
TI  - Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I
      kappa B kinase pathway to regulate the release of proinflammatory cytokines from
      human adipose tissue and skeletal muscle in vitro.
AB  - There is much evidence to indicate a role for adipocytokines in insulin
      resistance and/or type 2 diabetes mellitus. In experimental models, oral
      salicylates, through their ability to interfere with the nuclear factor-kappa B
      (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin
      resistance. The aim of this study was to investigate whether NF-kappa B regulates
      the release of adipocytokines in human adipose tissue and skeletal muscle. Human
      sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were
      incubated in the absence (control) or presence of two NF-kappa B inhibitors
      sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm).
      After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA
      binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta
      protein expression were assessed by ELISA and Western blotting, respectively. The
      incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8,
      resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose
      tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly
      inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding
      activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There
      was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or
      leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue
      and skeletal muscle expression of insulin receptor-beta. The data presented in
      this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a
      key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and
      skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide
      an alternative therapeutic strategy for regulating aberrant cytokine release and
      thereby alleviating insulin resistance in type 2 diabetes mellitus.

PMID- 15564334
TI  - Preservation of eumelanin hair pigmentation in proopiomelanocortin-deficient mice
      on a nonagouti (a/a) genetic background.
AB  - The original strain of proopiomelanocortin (POMC)-deficient mice (Pomc-/-) was
      generated by homologous recombination in 129X1/SvJ (A(w)/A(w))-derived embryonic
      stem cells using a targeting construct that deleted exon 3, encoding all the
      known functional POMC-derived peptides including alpha MSH, from the Pomc gene.
      Although these Pomc-/- mice exhibited adrenal hypoplasia and obesity similar to
      the syndrome of POMC deficiency in children, their agouti coat color was only
      subtly altered. To further investigate the mechanism of hair pigmentation in the
      absence of POMC peptides, we studied wild-type (Pomc+/+), heterozygous (Pomc+/-),
      and homozygous (Pomc-/-) mice on a nonagouti (a/a) 129;B6 hybrid genetic
      background. All three genotypes had similar black fur pigmentation with yellow
      hairs behind the ears, around the nipples, and in the perianal area
      characteristic of inbred C57BL/6 mice. Histologic and electron paramagnetic
      resonance spectrometry examination demonstrated that hair follicles in back skin
      of Pomc-/- mice developed with normal structure and eumelanin pigmentation;
      corresponding molecular analyses, however, excluded local production of alpha MSH
      and ACTH because neither Pomc nor putative Pomc pseudogene mRNAs were detected in
      the skin. Thus, 129;B6 Pomc null mutant mice produce abundant eumelanin hair
      pigmentation despite their congenital absence of melanocortin ligands. These
      results suggest that either the mouse melanocortin receptor 1 has sufficient
      basal activity to trigger and sustain eumelanogenesis in vivo or that redundant
      nonmelanocortin pathway(s) compensate for the melanocortin deficiency. Whereas
      the latter implies feedback control of melanogenesis, it is also possible that
      the two mechanisms operate jointly in hair follicles.

PMID- 15564335
TI  - The role of poly (adenosine 5'-diphosphate-ribose) polymerase in the response of
      pituitary tumor cells to reactive oxygen species.
AB  - As an enzyme implicated in the stress response, we investigated poly(ADP-ribose)
      polymerase (PARP) in the response of GH3 rat pituitary tumor cells to oxidants.
      These cells are unusual in that they undergo rapid cell death (90 min) with low
      doses of the prooxidant, H2O2 (50-200 microm), whereas at higher doses (1 mm),
      death occurs some hours later (4-5 h). Measurement of PARP activity shows that
      low doses of H2O2 (50-200 microm) fail to increase the activity of PARP, whereas
      at 0.5 and 1 mm, the enzyme becomes activated. In parallel with the activation of
      PARP, cellular ATP concentrations fall at high H2O2 doses and the PARP
      inhibitors, 3-aminobenzamide and nicotinamide (NIC) partially prevent this fall.
      Using NIC to inhibit PARP activity, we show that treatment of cells with NIC
      before the addition of H2O2 (0.5-1 mm), results in rapid cell death (90 min). In
      contrast, prior exposure to H2O2 (0.5-1 mm) for 1 h, before withdrawal and
      exposure to 1 mm NIC, allows cell survival for many hours. These data suggest
      that PARP is involved in blocking rapid death of GH3 cells in response to
      oxidants. In contrast to other cell types tested here, in which inhibitor studies
      show that PARP is activated at low H2O2 doses and this decreases the extent of
      apoptosis, GH3 cells are unable to sufficiently activate PARP to prevent rapid
      cell death.

PMID- 15564336
TI  - Chronic treatment with the monoamine oxidase inhibitor phenelzine increases
      hypothalamic-pituitary-adrenocortical activity in male C57BL/6 mice: relevance to
      atypical depression.
AB  - Atypical depression has been linked to low hypothalamic-pituitary-adrenocortical
      axis activity and exhibits physical and affective symptoms resembling those of
      glucocorticoid deficiency. Because atypical depression has also been defined by
      preferential responsiveness to monoamine oxidase inhibitors (MAO-I), we
      hypothesized that MAO-I reverse these abnormalities by interfering with
      glucocorticoid feedback and increasing hypothalamic-pituitary-adrenocortical
      activity. To test this hypothesis, we measured plasma hormones and ACTH
      secretagogue gene expression in male C57BL/6 mice treated chronically with saline
      vehicle or phenelzine, a representative MAO-I. Changes in glucocorticoid feedback
      were evaluated using adrenalectomized (ADX) mice with and without corticosterone
      replacement. Antidepressant efficacy was confirmed by decreased immobility during
      forced swim testing. Phenelzine significantly increased circadian nadir and
      postrestraint plasma corticosterone levels in sham-operated mice, an effect that
      correlated with increased adrenocortical sensitivity to ACTH. Phenelzine
      increased circadian nadir, but not poststress ACTH in ADX mice, suggesting that
      phenelzine augmented corticosterone secretion in sham-operated mice by increasing
      stimulation and decreasing feedback inhibition of hypothalamic-pituitary
      activity. Consistent with the latter possibility, phenelzine significantly
      increased plasma ACTH and paraventricular hypothalamus CRH mRNA in ADX,
      corticosterone-replaced mice. Phenelzine did not increase paraventricular
      hypothalamus CRH or vasopressin mRNA in ADX mice lacking corticosterone
      replacement. We conclude that chronic phenelzine treatment induces sustained
      increases in glucocorticoids by impairing glucocorticoid feedback, increasing
      adrenocortical responsiveness to ACTH, and increasing glucocorticoid-independent
      stimulation of hypothalamic-pituitary activity. The resulting drive for
      adrenocortical activity could account for the ability of MAO-I to reverse
      endocrine and psychiatric symptoms of glucocorticoid deficiency in atypical
      depression.

PMID- 15564337
TI  - Insulin alone increases hypothalamo-pituitary-adrenal activity, and diabetes
      lowers peak stress responses.
AB  - Diabetes is associated with increased basal hypothalamo-pituitary-adrenal (HPA)
      activity and impaired stress responsiveness. Previously, we demonstrated that the
      HPA response to hypoglycemia is significantly impaired in diabetic rats. In this
      study our goals were to 1) differentiate between the effects of hyperinsulinemia
      and those of hypoglycemia per se, and 2) establish whether diabetes lowers peak
      stress responses. Normal and streptozotocin-diabetic rats were subjected to
      hyperinsulinemic-euglycemic glucose clamps to evaluate central and peripheral
      responses. These were compared with peak ACTH and corticosterone responses to
      restraint and hypoglycemia. Hyperinsulinemia increased CRH and vasopressin mRNA,
      and plasma ACTH and corticosterone in normal and diabetic rats. In normal
      animals, insulin-induced activation of ACTH and corticosterone was lower than the
      responses during either restraint or hypoglycemia. In contrast, ACTH and
      corticosterone activation in diabetic rats was similar with all three stressors.
      Pituitary-adrenal axis activation in diabetic animals was also much lower
      compared with that in normal controls. The response to hyperinsulinemia
      (euglycemia) was associated with increases in glucocorticoid receptor mRNA in the
      anterior pituitary and paraventricular nucleus. Hippocampal mineralocorticoid
      receptor mRNA expression was increased in normal, but not in diabetic, animals.
      We speculate that the ability to appropriately match the HPA response to the
      potency of a stressor is related to the ability to alter hippocampal
      mineralocorticoid receptor expression. In diabetes, this ability is impaired;
      hence, maximal HPA activation is greatly diminished. This is a novel observation
      that may have important implications in the treatment of impaired
      counterregulatory mechanisms in human diabetes.

PMID- 15564338
TI  - Correlations between hypothalamus-pituitary-adrenal axis parameters depend on age
      and learning capacity.
AB  - Glucocorticoid hormones are released after activation of the hypothalamus
      pituitary-adrenal (HPA) axis and in the brain can modulate synaptic plasticity
      and memory formation. Clear individual differences in spatial learning and memory
      in the water maze allowed classification of groups of young (3 months) and aged
      (24 months) male Wistar rats as superior and inferior learners. We tested 1)
      whether measures of HPA activity are associated with cognitive functions and
      aging and 2) whether correlations of these measures depend on age and learning
      performance. Basal ACTH, but not corticosterone, was increased in aged rats, with
      the stress-induced ACTH response exaggerated in aged-inferior learners. Aged
      superior learners had lower expression of glucocorticoid receptor and CRH mRNA in
      the parvocellular paraventricular nucleus of the hypothalamus compared with all
      other groups. Hippocampal mineralocorticoid receptor and glucocorticoid receptor
      mRNAs differed modestly between groups, but steroid receptor coactivator and heat
      shock-protein 90 mRNAs were not different. Strikingly, correlations between HPA
      axis markers were dependent on grouping animals according to learning performance
      or age. CRH mRNA correlated with ACTH only in aged animals. Parvocellular
      arginine vasopressin mRNA was negatively correlated to basal corticosterone,
      except in aged-inferior learners. Corticosteroid receptor mRNA expression showed
      a number of correlations with other HPA axis regulators specifically in superior
      learners. In summary, the relationships between HPA axis markers differ for
      subgroups of animals. These distinct interdependencies may reflect adjusted set
      points of the HPA axis, resulting in adaptation (or maladaptation) to the
      environment and, possibly, an age-independent determination of learning ability.

PMID- 15564339
TI  - Steroid receptor coactivator-1 splice variants differentially affect
      corticosteroid receptor signaling.
AB  - The mechanisms of receptor- and cell-specific effects of the adrenal
      corticosteroid hormones via mineralo- (MRs) and glucocorticoid receptors (GRs)
      are still poorly understood. Because the expression levels of two splice variants
      of the steroid receptor coactivator-1 (SRC-1) 1a and 1e, can differ significantly
      in certain cell populations, we tested the hypothesis that their relative
      abundance could determine cell- and receptor-specific effects of corticosteroid
      receptor-mediated transcription. In transient transfections, we demonstrate three
      novel types of SRC-1a- and SRC-1e-specific effects for corticosteroid receptors.
      One is promoter dependence: SRC-1e much more potently coactivated transcription
      from several multiple response element-containing promoters. Mammalian 1-hydrid
      studies indicated that this likely does not involve promoter-specific coactivator
      recruitment. Endogenous phenylethanolamine-N-methyltransferase mRNA induction via
      GRs was also differentially affected by the splice variants. Another type is
      receptor specificity: responses mediated by the N-terminal part of the MR, but
      not the GR, were augmented by SRC-1e at synergizing response elements. SRC
      fragment SRC(988-1240) by the MR but not the GR N-terminal fragment in a 1-hybrid
      assay. The last type, for GRs, is ligand dependence. Due to effects on partial
      agonism of RU486-activated GRs, different ratios of SRC-1a and 1e can lead to
      large differences in the extent of antagonism of RU486 on GR-mediated
      transcription. Furthermore, we show that SRC-1e but not SRC-1a mRNA expression
      was regulated in the pituitary by corticosterone. We conclude that the cellular
      differences in SRC-1a to SRC-1e ratio demonstrated in vivo might be involved in
      cell-specific responses to corticosteroids in a promoter- and ligand-dependent
      way.

PMID- 15564340
TI  - Identification and localization of sodium-phosphate cotransporters in hepatocytes
      and cholangiocytes of rat liver.
AB  - Hepatocytes and cholangiocytes release ATP into bile, where it is rapidly
      degraded into adenosine and P(i). In rat, biliary P(i) concentration (0.01 mM) is
      approximately 100-fold and 200-fold lower than in hepatocytes and plasma,
      respectively, indicating active reabsorption of biliary P(i). We aimed to
      functionally characterize canalicular P(i) reabsorption in rat liver and to
      identify the involved P(i) transport system(s). P(i) transport was determined in
      isolated rat canalicular liver plasma membrane (LPM) vesicles using a rapid
      membrane filtration technique. Identification of putative P(i) transporters was
      performed with RT-PCR from liver mRNA. Phosphate transporter protein expression
      was confirmed by Western blotting in basolateral and canalicular LPM and by
      immunofluorescence in intact liver. Transport studies in canalicular LPM vesicles
      demonstrated sodium-dependent P(i) uptake. Initial P(i) uptake rates were
      saturable with increasing P(i) concentrations, exhibiting an apparent K(m) value
      of approximately 11 muM. P(i) transport was stimulated by an acidic
      extravesicular pH and by an intravesicular negative membrane potential. These
      data are compatible with transport characteristics of sodium-phosphate
      cotransporters NaPi-IIb, PiT-1, and PiT-2, of which the mRNAs were detected in
      rat liver. On the protein level, NaPi-IIb was detected at the canalicular
      membrane of hepatocytes and at the brush-border membrane of cholangiocytes. In
      contrast, PiT-1 and PiT-2 were detected at the basolateral membrane of
      hepatocytes. We conclude that NaPi-IIb is most probably involved in the
      reabsorption of P(i) from primary hepatic bile and thus might play an important
      role in the regulation of biliary P(i) concentration.

PMID- 15564341
TI  - The INTERHEART study: intersection between behavioral and general medicine.

PMID- 15564342
TI  - Depression is a risk factor for mortality in coronary heart disease.

PMID- 15564343
TI  - Depression as a risk factor for mortality in patients with coronary heart
      disease: a meta-analysis.
AB  - BACKGROUND: Prospective studies on physically healthy subjects have shown an
      association between depression and the subsequent development of coronary heart
      disease (CHD). The relative risk in meta-analytic aggregation is 1.64 (confidence
      interval [CI], 1.29-2.08) for any CHD event. However, the adverse impact of
      depression on CHD patients has not yet been the subject of a meta-analysis.
      OBJECTIVE: To quantify the impact of depressive symptoms (eg, BDI, HADS) or
      depressive disorders (major depression) on cardiac or all-cause mortality. We
      analyzed the strength of the relationship, the time dependency, and the
      differences in studies using depressive symptoms or a clinical diagnosis as
      predictors of mortality. METHOD: English and German language databases (Medline,
      PsycInfo, PSYNDEX) from 1980 to 2003 were searched for prospective cohort
      studies. Sixty-two publications were identified. The inclusion criteria were met
      by 29 publications reporting on 20 studies. A random model was used to estimate
      the combined overall effect as crude odds ratios (OR) or adjusted hazard ratios
      (HR [adj]). RESULTS: Depressive symptoms increase the risk of mortality in CHD
      patients. The risk of depressed patients dying in the 2 years after the initial
      assessment is two times higher than that of nondepressed patients (OR, 2.24; 1.37
      3.60). This negative prognostic effect also remains in the long-term (OR, 1.78;
      1.12-2.83) and after adjustment for other risk factors (HR [adj], 1.76; 1.27
      2.43). The unfavorable impact of depressive disorders was reported for the most
      part in the form of crude odds ratios. Within the first 6 months, depressive
      disorders were found to have no significant effect on mortality (OR, 2.07; CI,
      0.82-5.26). However, after 2 years, the risk is more than two times higher for
      CHD patients with clinical depression (OR, 2.61; 1.53-4.47). Only three studies
      reported adjusted hazard ratios for clinical depression and supported the results
      of the bivariate models. CONCLUSIONS: Depressive symptoms and clinical depression
      have an unfavorable impact on mortality in CHD patients. The results are limited
      by heterogeneity of the results in the primary studies. There is no clear
      evidence whether self-report or clinical interview is the more precise predictor.
      Nevertheless, depression has to be considered a relevant risk factor in patients
      with CHD.

PMID- 15564344
TI  - Prognostic association of depression following myocardial infarction with
      mortality and cardiovascular events: a meta-analysis.
AB  - OBJECTIVE: To assess the association of depression following myocardial
      infarction (MI) and cardiovascular prognosis. METHODS: The authors performed a
      meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975
      2003) combined with crossreferencing without language restrictions. The authors
      selected prospective studies that determined the association of depression with
      the cardiovascular outcome of MI patients, defined as mortality and
      cardiovascular events within 2 years from index MI. Depression had to be assessed
      within 3 months after MI using established psychiatric instruments. A quality
      assessment was performed. RESULTS: Twenty-two papers met the selection criteria.
      These studies described follow up (on average, 13.7 months) of 6367 MI patients
      (16 cohorts). Post-MI depression was significantly associated with all-cause
      mortality (odds ratio [OR], fixed 2.38; 95% confidence interval [CI], 1.76-3.22;
      p <.00001) and cardiac mortality (OR fixed, 2.59; 95% CI, 1.77-3.77; p <.00001).
      Depressive MI patients were also at risk for new cardiovascular events (OR
      random, 1.95; 95% CI, 1.33-2.85; p = .0006). Secondary analyses showed no
      significant effects of follow-up duration (0-6 months or longer) or assessment of
      depression (self-report questionnaire vs. interview). However, the year of data
      collection (before or after 1992) tended to influence the effect of depression on
      mortality (p = .08), with stronger associations found in the earlier studies (OR,
      3.22; 95% CI, 2.14-4.86) compared with the later studies (OR, 2.01; 95% CI, 1.45
      2.78). CONCLUSIONS: Post-MI depression is associated with a 2- to 2.5-fold
      increased risk of impaired cardiovascular outcome. The association of depression
      with cardiac mortality or all-cause mortality was more pronounced in the older
      studies (OR, 3.22 before 1992) than in the more recent studies (OR, 2.01 after
      1992).

PMID- 15564345
TI  - Depressive symptoms and mortality risk in a national sample: confounding effects
      of health status.
AB  - OBJECTIVE: We examined the association between depressive symptoms and all-cause
      mortality in a population sample. Published findings on the relation between
      depressive symptoms and mortality risk point to an inconsistent association and
      one that is likely influenced by health status. Few studies have assessed this
      relation in randomly selected population samples. METHODS: Participants were 3617
      noninstitutionalized adults, age 25 years or older, from the Americans' Changing
      Lives Study, an ongoing longitudinal study of a nationally representative sample.
      Depressive symptoms were measured by the 11-item version of the Center for
      Epidemiological Studies Depression Scale (CES-D). Cox proportional hazards models
      estimated the relative risk of mortality as a function of the CES-D scores at
      baseline. RESULTS: In 7.5 years of follow-up, 542 deaths occurred. Each 1
      standard unit increase on the CES-D predicted a 21% increased risk of all-cause
      mortality, adjusting for age, gender, and race (hazard ratio = 1.21, 95%
      confidence interval = 1.08 to 1.36, p = .001). This association was weakened
      somewhat following adjustment for education, income, body mass index, smoking and
      alcohol consumption (hazard ratio = 1.13, 95% confidence interval = 0.99 to 1.28,
      p = .06). However, control for self-reported functional limitations or chronic
      health conditions at baseline effectively eliminated the relationship. Analyses
      limited to participants with good to excellent health or no functional
      impairments at baseline showed no association between depressive symptoms and
      subsequent mortality risk. Secondary analyses showed no association between
      depressive symptoms and cardiovascular mortality. CONCLUSIONS: These findings
      from a randomly selected, nationally representative sample do not support the
      hypothesis that depressive symptoms are independently related to mortality in the
      general population, after adequate adjustment for the confounding effects of
      physical health status.

PMID- 15564346
TI  - Anxiety and depression in patients with pulmonary hypertension.
AB  - OBJECTIVE: This is the first study that investigates the prevalence and actual
      treatment of anxiety, depression, and other mental disorders in patients with
      pulmonary hypertension (PH). The prevalence of mental disorders in patients with
      PH was compared with parallel groups of primary care patients and patients with
      inflammatory rheumatic diseases, and the relationship between functional status
      and prevalence of mental disorders was determined. METHODS: The patient group
      with PH (70.1% female; mean age, 47.8 +/- 12.7 years) and the two comparison
      groups, which were matched by age and sex, consisted of 164 patients each.
      Patients completed self-administered instruments, including the Patient Health
      Questionnaire for the diagnosis of mental disorders. New York Heart Association
      (NYHA) functional class was assessed in all patients with PH. RESULTS: Thirty
      five percent of the patients with PH suffered from mental disorders, with the
      most common being major depressive disorder (15.9%) and panic disorder (10.4%).
      Both panic disorder and panic attacks were significantly more prevalent in
      patients with PH than in either patients with inflammatory rheumatic diseases or
      primary care patients. The prevalence of mental disorders in patients with PH
      increased significantly with functional impairment, from 17.7% (NYHA class I) to
      61.9% (NYHA class IV). Only 24.1% of the patients with PH with mental disorders
      were receiving psychopharmacological or psychotherapeutic treatment. CONCLUSIONS:
      Anxiety and depression are frequent in patients with PH and increase as the
      severity of disease progresses. Given the fact that safe and efficacious
      treatments of mental disorders are available, greater importance should be
      attached to the diagnosis and treatment of these conditions in patients with PH.

PMID- 15564347
TI  - Comorbid depression and anxiety in fibromyalgia syndrome: relationship to somatic
      and psychosocial variables.
AB  - OBJECTIVE: The prevalence as well as predictors of psychiatric disorders
      (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] axis
      I and II) in patients with fibromyalgia syndrome (FMS) was evaluated. METHOD: One
      hundred fifteen patients with FMS participated in the Structured Clinical
      Interview for DSM-IV to assess current mental disorders. In addition, patients
      completed standardized questionnaires regarding pain, pain impact, anxiety,
      depression, posttraumatic stress disorder-like symptoms, and sexual and physical
      abuse. RESULTS: Patients were grouped into one of three psychosocial subgroups
      based on responses to the Multidimensional Pain Inventory (MPI)-Dysfunctional
      (DYS), Interpersonally Distressed (ID), and Adaptive Copers (AC). Axis I
      diagnoses were present in 74.8% of the participants overall with the DYS subgroup
      mainly reporting anxiety and the ID group mood disorders. The AC group showed
      little comorbidity. Axis II diagnoses were present in only 8.7% of the FMS
      sample. CONCLUSION: These results suggest that FMS is not a homogeneous
      diagnosis, but shows varying proportions of comorbid anxiety and depression
      dependent on psychosocial characteristics of the patients. The results
      demonstrate the importance of not treating patients with FMS as a homogeneous
      group. Assessment should not only examine the presence of widespread pain and the
      number of tender points, but also the presence of affective distress. Treatment
      should focus both on physical and emotional dysfunction.

PMID- 15564348
TI  - The association between anxiety, depression, and somatic symptoms in a large
      population: the HUNT-II study.
AB  - OBJECTIVE: Somatic symptoms are prevalent in the community, but at least one
      third of the symptoms lack organic explanation. Patients with such symptoms have
      a tendency to overuse the health care system with frequent consultations and have
      a high degree of disability and sickness compensation. Studies from clinical
      samples have shown that anxiety and depression are prevalent in such functional
      conditions. The aim of this study is to examine the connection between anxiety,
      depression, and functional somatic symptoms in a large community sample. METHOD:
      The HUNT-II study invited all inhabitants aged 20 years and above in Nord
      Trondelag County of Norway to have their health examined and sent a questionnaire
      asking about physical symptoms, demographic factors, lifestyle, and somatic
      diseases. Anxiety and depression were recorded by the Hospital Anxiety and
      Depression Scale. Of those invited, 62,651 participants (71.3%) filled in the
      questionnaire. A total of 10,492 people were excluded due to organic diseases,
      and 50,377 were taken into the analyses. RESULTS: Women reported more somatic
      symptoms than men (mean number of symptoms women/men: 3.8/2.9). There was a
      strong association between anxiety, depression, and functional somatic symptoms.
      The association was equally strong for anxiety and depression, and a somewhat
      stronger association was observed for comorbid anxiety and depression. The
      association of anxiety, depression, and functional somatic symptoms was equally
      strong in men and women (mean number of somatic symptoms men/women in anxiety:
      4.5/5.9, in depression: 4.6/5.9, in comorbid anxiety and depression: 6.1/7.6, and
      in no anxiety or depression: 2.6/3.6) and in all age groups. The association
      between number of somatic symptoms and the total score on Hospital Anxiety and
      Depression Scale was linear. CONCLUSION: There was a statistically significant
      relationship between anxiety, depression, and functional somatic symptoms,
      independent of age and gender.

PMID- 15564349
TI  - The relationship of somatization and depression to experimental pain response in
      women with temporomandibular disorders.
AB  - OBJECTIVE: Patients with temporomandibular pain disorders (TMD) have greater
      experimental pain perception when compared with pain-free controls. Common
      psychological features of TMD include somatization and depression. The impact of
      depression on experimental pain perception has received considerable attention.
      However, the role of somatization on experimental pain in a chronic pain
      population has not been explored. METHODS: Fifty-six women with TMD and 59 pain
      free controls underwent three experimental pain procedures, including palpation
      at fixed amounts of pressure, pressure pain thresholds, and an ischemic pain
      task. Levels of depression and somatization were assessed using the Research
      Diagnostic Criteria for TMD. Multiple regression analyses were performed to
      determine the extent to which depression and somatization were associated with
      experimental pain response. RESULTS: After controlling for characteristic pain
      intensity and depression, somatization explained a significant proportion of
      variance in numbers of masticatory sites rated as painful (R2 change = 6.7%, p =
      .046) with the full model explaining 16.4% of the variance (p = .024). This did
      not meet an adjusted level of statistical significance (p = .008). After
      controlling for characteristic pain, only depression added significantly to the
      model predicting ischemic pain threshold and tolerance. The full models including
      characteristic pain and depression explained 49% and 20% of the variance in
      ischemic pain threshold and tolerance, respectively. CONCLUSIONS: These findings
      suggest that depression and somatization are associated with different measures
      of experimental pain. Somatization may be related to more attentional and
      perceptual measures of clinically relevant pain while depression may be related
      to more behavioral measures of pain.

PMID- 15564350
TI  - Chest pain in patients with cardiac and noncardiac disease.
AB  - OBJECTIVE: To describe factors influencing chest pain expression in patients with
      cardiac or noncardiac disease. METHODS: The authors conducted a case presentation
      and review of literature. RESULTS: Causes of chest pain are diverse. Psychologic
      factors influence chest pain expression commonly in patients with or without
      cardiac disease. CONCLUSIONS: Physicians and other therapists must be aware of
      psychologic influences on chest pain expression to provide optimal treatment to
      their patients.

PMID- 15564351
TI  - Risk factors, confounding, and the illusion of statistical control.
AB  - When experimental designs are premature, impractical, or impossible, researchers
      must rely on statistical methods to adjust for potentially confounding effects.
      Such procedures, however, are quite fallible. We examine several errors that
      often follow the use of statistical adjustment. The first is inferring a factor
      is causal because it predicts an outcome even after "statistical control" for
      other factors. This inference is fallacious when (as usual) such control involves
      removing the linear contribution of imperfectly measured variables, or when some
      confounders remain unmeasured. The converse fallacy is inferring a factor is not
      causally important because its association with the outcome is attenuated or
      eliminated by the inclusion of covariates in the adjustment process. This
      attenuation may only reflect that the covariates treated as confounders are
      actually mediators (intermediates) and critical to the causal chain from the
      study factor to the study outcome. Other problems arise due to mismeasurement of
      the study factor or outcome, or because these study variables are only proxies
      for underlying constructs. Statistical adjustment serves a useful function, but
      it cannot transform observational studies into natural experiments, and involves
      far more subjective judgment than many users realize.

PMID- 15564352
TI  - Cortisol, hunger, and desire to binge eat following a cold stress test in obese
      women with binge eating disorder.
AB  - OBJECTIVE: Increased basal cortisol levels have been found in bulimia nervosa.
      After stress, increased cortisol levels have been associated with increased food
      intake in healthy women. Therefore, we assessed cortisol, hunger, and desire to
      binge eat after a cold pressor test (CPT) among women with binge eating disorder
      (BED). METHODS: Twenty-two obese (body mass index [BMI] = 36.7 +/- 6.5 SD)
      females (11 non-BED, 11 BED) completed the Zung depression scale and underwent
      the CPT, hand submerged in ice water for 2 minutes. Over 60 minutes, periodic
      ratings of hunger and desire to binge eat were obtained, just before blood draws
      for cortisol, as well as insulin. On a separate day, participants had a 1-mg oral
      dexamethasone suppression test (DST). RESULTS: The BED group had higher
      depression scores than the non-BED (p = .04), but depression was not a
      significant covariate for the cortisol response or to DST. After controlling for
      contraceptive use (n = 3), the BED group had higher basal cortisol than the non
      BED group (p = .03), but cortisol did not differ after DST (p = .40). The BED
      group had nearly significant greater cortisol AUC after the CPT (p = .057) after
      controlling for insulin AUC and contraceptive use (p = .057). The BED group also
      had greater AUC for hunger (p = .03) and desire to binge eat (p = .02) after the
      CPT. CONCLUSION: These findings support our hypothesis of a hyperactive HPA-axis
      in BED, which may contribute to greater hunger and binge eating.

PMID- 15564353
TI  - Social networks are associated with lower mortality rates among women with
      suspected coronary disease: the National Heart, Lung, and Blood Institute
      Sponsored Women's Ischemia Syndrome Evaluation study.
AB  - OBJECTIVE: To examine the association between social relationships measured by
      the Social Network Scale and coronary artery disease (CAD) risk and mortality
      among a sample of women with suspected CAD. METHODS: Five hundred three women
      (mean age, 59 years) with suspected CAD warranting clinical investigation
      completed a diagnostic protocol including psychosocial testing, CAD risk factor
      assessment, and quantitative coronary angiography. Patients were subsequently
      followed for a mean of 2.3 years to track all-cause mortality. RESULTS: Women
      reporting higher social network scores showed a consistent pattern of reduced
      coronary artery disease risk, including lower blood glucose levels (r = -0.11; p
      = .03), lower smoking rates (odds ratio [OR] = 0.81; 95% confidence interval [CI]
      = 0.71-0.93; p = .002), lower waist-hip ratios (r = -0.18; p < .01), and lower
      rates of hypertension (OR = 0.90; 95% CI = 0.81-0.99; p = .04) and diabetes (OR =
      0.83; 95% CI = 0.73-0.94; p = .004). Based on quantitative angiogram findings,
      high social network scorers also had less severe CAD (mean angiogram stenosis
      value, 40.8 vs. 27.2 for low and high scoring social network groups,
      respectively; p < .001). Finally, mortality rates over follow-up showed a dose
      response pattern in relation to quartile scorers on the Social Network Index,
      with low scorers showing more than twice the death rate of high scorers (relative
      risk = 2.4; p = .03). CONCLUSIONS: Among a cohort of women with suspected CAD,
      smaller social circles were associated with increased CAD risk factors and
      mortality, an effect that appeared to be explained largely by income level. The
      findings extend previous studies of social network effects on health by
      highlighting risk among women with suspected CAD, and suggest mechanisms for
      further study.

PMID- 15564354
TI  - The Families In Recovery From Stroke Trial (FIRST): primary study results.
AB  - OBJECTIVE: Social support and family ties are strong predictors of functional
      recovery after stroke; however, development of successful psychosocial
      intervention programs has been difficult. This study examined whether a family
      systems intervention designed to influence social support and self-efficacy
      affects functional outcome in older stroke patients. METHODS: Two hundred ninety
      one community-residing survivors of ischemic stroke or nontraumatic cerebral
      hemorrhage from eight acute-care hospitals and rehabilitation centers were
      randomized to either psychosocial intervention (PSI) or usual care (UC). PSI
      involved up to 16 sessions conducted in the home by a mental health worker.
      Functional recovery (measured by the Barthel Index [BI] at 6 months
      postrandomization, inability to assess functioning because of illness or death)
      was the primary end point. RESULTS: Functional recovery did not differ between UC
      and PSI in intention-to-treat analyses. In adjusted logistic regression, the odds
      of being functionally independent at 6 months was 60% higher in the intervention
      group, but this difference was not statistically significant (p = .31). Subgroup
      analyses revealed that PSI may be more effective in subjects with better
      psychologic and cognitive functioning and who required less inpatient
      rehabilitation. CONCLUSION: This study does not provide evidence for the efficacy
      of psychosocial intervention to improve functional recovery in stroke. Although
      PSI showed greater improvement than UC, the differences were not statistically
      significant.

PMID- 15564355
TI  - Psychological traits and emotion-triggering of ICD shock-terminated arrhythmias.
AB  - OBJECTIVE: We have previously reported on the triggering of arrhythmia and hence,
      implanted cardioverter-defibrillators (ICD) shock by strong emotion. The purpose
      of the present study was to examine whether concordant psychological traits
      distinguish patients who experience emotion-triggered ICD shock. METHODS: Two
      hundred forty ICD patients completed the Speilberger Trait Anxiety and Anger
      Inventories and Anger Expression Scale, and the abridged Cook-Medley Hostility
      Scale approximately 2 months after ICD implantation. Patients were also given a
      structured diary to record mood states retrospectively for the period 0 to 15
      minutes preceding ICD shock and for a period corresponding to the same time of
      day 1 week later. Patients who reported emotion-triggered ICD shock were compared
      on concordant psychological measures to patients who did not. RESULTS: Patients
      who reported at least moderate anger in the 0 to 15 minutes before ICD shock
      scored significantly higher on Speilberger Trait Anger (24.18 +/- 3.97 vs. 17.04
      +/- 2.17, p < .0001), and Cook-Medley Aggressive Responding (5.76 +/- 0.75 vs.
      3.96 +/- 1.30, p < .0001) and Hostile Affect (3.59 +/- 0.80 vs. 2.04 +/- 1.02, p
      < .0001), and lower on Speilberger Anger Control (7.94 +/- 1.43 vs. 10.64 +/-
      1.19, p < .001) than those who did not. In multivariate analysis, only Trait
      Anger remained a significant predictor of anger-triggered shock (chi2 = 7.10, p <
      .008). Patients who reported at least moderate anxiety in the 0 to 15 minutes
      before ICD shock scored significantly higher on Speilberger Anxiety (22.43 +/-
      1.65 vs. 19.96 +/- 1.71, p < .0001) than those who did not. CONCLUSION: Stable
      psychological factors are associated with risk for ICD-shock triggered by
      concordant strong emotion.

PMID- 15564356
TI  - Trait anger and the metabolic syndrome predict progression of carotid
      atherosclerosis in healthy middle-aged women.
AB  - OBJECTIVE: Hostility may predict coronary heart disease morbidity and mortality,
      as well as the metabolic syndrome. We tested to see if high levels of the
      attitudinal and emotional aspects of hostility lead to progression of carotid
      atherosclerosis in women and if the metabolic syndrome is a mediator of the
      association. METHODS: Two hundred nine healthy women were followed during the
      perimenopausal and postmenopausal periods. Carotid artery ultrasound scans
      measured intima-media thickness (IMT) an average 7.4 (SD = 0.9, range 4.2-10.8)
      and 10.5 years (SD = 1.1, range = 6.9-13.0) after baseline. Hostility was
      measured at baseline and at the first carotid scan with Spielberger Trait Anger
      (being angry frequently) and Anger In (suppressing angry feelings) scales, and
      the Cook-Medley Hostility Inventory (hostile, cynical attitudes toward others).
      Metabolic syndrome was measured at the study entry and through the second carotid
      scan. RESULTS: Baseline Trait Anger scores predicted an increase in IMT across 3
      years (p < .05) and predicted the risk for developing the metabolic syndrome (p <
      .05). The risk for developing the metabolic syndrome, in turn, predicted an
      increase in IMT across 3 years (p < .05). Anger suppression and cynical attitudes
      were not associated with progression of carotid atherosclerosis. CONCLUSION:
      Anger predicts progression of carotid atherosclerosis, and the metabolic syndrome
      may mediate this association. Women who experience angry feelings frequently may
      benefit from interventions aimed at reducing anger and reducing the metabolic
      syndrome components early in the natural history of atherosclerosis.

PMID- 15564357
TI  - Impact of meditation on resting and ambulatory blood pressure and heart rate in
      youth.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of a meditation
      program on resting and ambulatory blood pressure and heart rate in youth.
      METHODS: Data from 73 middle school students (age 12.3 +/- 0.6 years) randomly
      assigned by classroom to either meditation (N = 34) or health education control
      (N = 39) groups were analyzed. The meditation groups engaged in 10-minute
      sessions at school and at home after school each day for 3 months. Resting
      (seated) systolic blood pressure, diastolic blood pressure, and heart rate
      measurements were obtained pretest and posttest on three consecutive school days
      using Dinamap 1846SX monitors. Ambulatory systolic blood pressure, ambulatory
      diastolic blood pressure, and ambulatory heart rate were recorded over 24-hour
      periods at pretest and posttest every 20 minutes during self-reported normal
      waking hours and every 30 minutes during self-reported normal sleep hours using
      Spacelabs 90207 monitors. RESULTS: Significant (p < .05) differences in average
      change from pretest to posttest were found between the meditation and health
      education control groups for resting systolic blood pressure (-2.7 vs. 1.1 mm
      Hg), daytime ambulatory systolic blood pressure after school (-2.0 vs. 3.6 mm
      Hg), daytime ambulatory diastolic blood pressure after school (0.1 vs. 4.3 mm
      Hg), and daytime ambulatory heart rate after school (-5.3 vs. 0.3 bpm).
      CONCLUSION: These findings demonstrate the potential beneficial impact of
      meditation on blood pressure and heart rate in the natural environment in healthy
      normotensive youth.

PMID- 15564358
TI  - Acute threat to the social self: shame, social self-esteem, and cortisol
      activity.
AB  - OBJECTIVE: Our Social Self Preservation Theory asserts that situations which
      threaten the "social self" (ie, one's social value or standing) elicit increased
      feelings of low social worth (eg, shame), decrements in social self-esteem, and
      increases in cortisol, a hormone released by the hypothalamic-pituitary-adrenal
      axis. To test our theoretical premise, cognitive, emotional, and physiological
      responses to the performance of laboratory stressor tasks were compared in
      participants who performed these tasks in the presence or absence of social-self
      threat. METHODS: Pre- and poststressor emotion, self-esteem, heart rate, blood
      pressure, and salivary cortisol were compared in 81 participants randomly
      assigned to complete speech and mental arithmetic stress tasks with social
      evaluation present (n = 41) or absent (n = 40). RESULTS: As hypothesized,
      participants in the social evaluation condition exhibited greater increases in
      shame and greater decrements in social self-esteem. Other psychological states
      (eg, anxiety, performance self-esteem) did not show differential changes as a
      function of the social context. Salivary cortisol increased in social evaluation
      condition participants but did not increase in participants who performed the
      same tasks in the absence of social evaluation. Cortisol increases were greater
      in participants who experienced greater increases in shame and greater decreases
      in social self-esteem under social-self threat. CONCLUSION: Threat to the social
      self is an important elicitor of shame experience, decreases in social self
      esteem and cortisol increases under demanding performance conditions. Cortisol
      changes may be specifically tied to the experience of emotions and cognitions
      reflecting low self-worth in this context.

PMID- 15564359
TI  - Microarousals during sleep are associated with increased levels of lipids,
      cortisol, and blood pressure.
AB  - OBJECTIVE: Previous work has demonstrated a link between restricted sleep and
      risk indicators for cardiovascular and metabolic disease, such as levels of
      cortisol, lipids, and glucose. The present study sought to identify relations
      between polysomnographic measures of disturbed sleep (frequency of arousals from
      sleep, total sleep time, and sleep efficiency) and a number of such indicators. A
      second purpose was to relate the number of arousals to mood, stress, work
      characteristics, and other possible predictors in daily life. METHODS: Twenty
      four people (10 men, 14 women; mean age 30 years), high vs. low on burnout, were
      recruited from a Swedish IT company. Polysomnographically recorded sleep was
      measured at home before a workday. Blood pressure, heart rate, morning blood
      sample, and saliva samples of cortisol were measured the subsequent working day.
      They were also recorded for diary ratings of sleep and stress, and a
      questionnaire with ratings of sleep, stress, work conditions, and mood was
      completed. RESULTS: A stepwise regression analysis using sleep parameters as
      predictors brought out number of arousals as the best predictor of morning
      cortisol (serum and saliva), heart rate, systolic and diastolic blood pressure,
      total cholesterol, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)
      cholesterol, and LDL/HDL-ratio. Work stress/unclear boundaries between work and
      leisure time was the best predictor of arousals among the stress variables.
      CONCLUSION: Consistent with sleep restriction experiments, sleep fragmentation
      was associated with elevated levels of metabolic and cardiovascular risk
      indicators of stress-related disorders. Number of arousals also seems to be
      related to workload/stress.

PMID- 15564360
TI  - Sleep deprivation affects thermal pain thresholds but not somatosensory
      thresholds in healthy volunteers.
AB  - OBJECTIVE: Sleep disturbances have been thought to augment pain. Sleep
      deprivation has been proven to produce hyperalgesic effects. It is still unclear
      whether these changes are truly specific to pain and not related to general
      changes in somatosensory functions. The aim of the present study was to evaluate
      the effect of total sleep deprivation on thermal pain thresholds (heat, cold) and
      pain complaints. Thermal detection thresholds (warmth, cold) were included as
      covariates to determine the contribution of somatosensory functions to changes in
      pain processing. METHODS: Twenty healthy volunteers were randomly assigned either
      to two nights of total sleep deprivation or to two nights of undisturbed night
      sleep. Sleep deprivation nights were separated by two days with normal night
      sleep. Heat and cold pain thresholds as well as warmth and cold detection
      thresholds were measured by use of a peltier thermode in the evening before and
      the morning after each deprivation or control night. Pain complaints were
      examined by use of a questionnaire in parallel. RESULTS: During treatment nights,
      sleep deprivation produced a significant overnight decrease in heat pain
      thresholds. Cold pain thresholds tended to decrease also during sleep
      deprivation, whereas the warmth and cold detection thresholds remained
      unaffected. Accordingly, no substantial contributions of the changes in thermal
      detection thresholds to the changes in thermal pain thresholds were determined by
      regression analyses. Pain complaints were not induced by sleep deprivation.
      CONCLUSIONS: The present findings suggest that sleep deprivation produces
      hyperalgesic changes that cannot be explained by nonspecific alterations in
      somatosensory functions.

PMID- 15564361
TI  - Factors associated with the psychological impact of severe acute respiratory
      syndrome on nurses and other hospital workers in Toronto.
AB  - OBJECTIVES: A survey was conducted to measure psychological stress in hospital
      workers and measure factors that may have mediated acute traumatic responses.
      METHODS: A self-report survey was completed by 1557 healthcare workers at three
      Toronto hospitals in May and June 2003. Psychological stress was measured with
      the Impact of Event Scale. Scales representing attitudes to the outbreak were
      derived by factor analysis of 76 items probing attitudes to severe acute
      respiratory syndrome. The association of Impact of Event Scale scores to job role
      and contact with severe acute respiratory syndrome patients was tested by
      analysis of variance. Between-group differences in attitudinal scales were tested
      by multivariate analysis of variance. Attitudinal scales were tested as factors
      mediating the association of severe acute respiratory syndrome patient contact
      and job role with total Impact of Event Scale by linear regression. RESULTS:
      Higher Impact of Event Scale scores are found in nurses and healthcare workers
      having contact with patients with severe acute respiratory syndrome. The
      relationship of these groups to the Impact of Event Scale score is mediated by
      three factors: health fear, social isolation, and job stress. CONCLUSIONS:
      Although distress in response to the severe acute respiratory syndrome outbreak
      is greater in nurses and those who care for patients with severe acute
      respiratory syndrome, these relationships are explained by mediating variables
      that may be available for interventions to reduce stress in future outbreaks. In
      particular, the data suggest that the targets of intervention should include job
      stress, social isolation, and health fear.

PMID- 15564362
TI  - Respiratory symptoms and mental disorders among youth: results from a
      prospective, longitudinal study.
AB  - OBJECTIVE: To determine the relationship between respiratory symptoms and mental
      disorders among youth in the community, and to investigate possible mechanisms of
      these linkages. METHODS: Data were drawn from the Oregon Adolescent Depression
      Project (n = 1,709), a longitudinal study of adolescents in the community.
      Multiple logistic regression analyses were used to examine the cross-sectional
      and longitudinal associations between respiratory symptoms and mental disorders
      at baseline, and linkages between respiratory symptoms at baseline and the onset
      of specific mental disorders at follow-up. Additional analyses were performed to
      examine the strength and specificity of the relationship between respiratory
      symptoms and mental disorders. The potential roles of hypochondriasis, functional
      impairment, and cigarette smoking in the associations between respiratory
      symptoms and mental disorders were investigated. RESULTS: Respiratory symptoms
      were associated with a significantly increased odds of any mental disorder (odds
      ratio (OR) = 1.9), specifically any depressive disorder (OR = 1.9), major
      depression (OR = 1.9), any substance use disorders (OR = 1.6), panic attacks (OR
      = 3.1), and attention deficit/hyperactivity disorder (ADHD) (OR = 5.8) at
      baseline. Respiratory symptoms at between 1987 and 1989 (Time 1) were associated
      with significantly increased risk of the onset of any mental disorder a year
      later (Time 2) (OR = 2.1). While demographic differences, hypochondriasis,
      functional impairment, and cigarette smoking contributed to the relationships
      between respiratory symptoms and mental disorders, these associations persisted
      after adjusting for these factors. CONCLUSIONS: The results suggest evidence of
      an association between respiratory symptoms and mental disorders among youth in
      the community. While demographic differences, hypochondriasis, functional
      impairment, and cigarette smoking may contribute to the linkage, these factors do
      not appear to completely explain the association. Future studies that can
      replicate these findings and include an examination of other possible mechanisms
      for these patterns of comorbidity, such as shared familial vulnerability or other
      environmental risk factors (e.g., childhood behavioral risk factors), are needed
      next.

PMID- 15564363
TI  - Psychosocial factors and the response to influenza vaccination in older adults.
AB  - OBJECTIVE: We examined the influence of psychological state (depression, negative
      affect, perceived stress) and social support on pre- and post-vaccination
      response to influenza vaccine. METHODS: Venous blood was drawn from 37 nursing
      home residents before and following injection of the trivalent influenza vaccine
      (comprised of the New Caledonia (NC), Hong Kong (HK), and Panama (Pan) strains of
      flu). The Geriatric Depression Scale, Perceived Stress Scale, Positive and
      Negative Affect Schedule, and Multidimensional Scale of Perceived Social Support
      were completed following the initial blood draw. RESULTS: Social support and
      perceived stress were correlated with pre-vaccine antibody responses to two of
      the three vaccine components (HK and NC). Social support was negatively
      correlated with both pre- and post-vaccine titers to Pan. Depression, positive
      affect, and negative affect were not related to vaccine response. CONCLUSIONS:
      Perceived stress and social support influence the rate of decline of antibody
      titers to previous exposures to some strains of influenza occurring either
      naturally or via deliberate vaccination.

PMID- 15564364
TI  - Biopsychosocial predictors of health-related quality of life in patients with
      chronic hepatitis C.
AB  - OBJECTIVES: To assess biopsychosocial predictors of health-related quality of
      life (HRQOL) in patients with chronic hepatitis C. METHODS: In 94 consecutive
      patients with chronic hepatitis C attending a liver center, HRQOL was assessed by
      the Medical Outcome Study Short Form Health Survey 36 (SF-36) and by the German
      version of the Chronic Liver Disease Questionnaire. The predictive effect on
      HRQOL of disease-related worries measured by the worry subscale of the Chronic
      Liver Disease Questionnaire, psychiatric comorbidity (defined by at least one
      Hospital Anxiety and Depression Scale German Version Score > or =11), the Child
      Pugh score in case of cirrhosis, interferon therapy, and active medical
      comorbidities was assessed by a multiple regression analysis. RESULTS: From 88
      patients (age, 48.6 +/- 14.6 years; 50% female), 62 (70%) had no cirrhosis, 15
      (17%) Child A, 5 (6%) Child B, and 6 patients (7%) Child C cirrhosis. The mental
      summary score of SF-36 was predicted by the amount of disease-related worries
      (corrected R2 = 0.33; beta = 3.2; p < .001) and psychiatric comorbidity
      (corrected R2 = 0.42; beta = -9.0; p < .001), by the physical summary score of SF
      36 by the amount of disease related worries (corrected R2 = 0.33; beta = 4.0; p <
      .001), and by the number of active medical comorbidities (corrected R2 = 0.39;
      beta = -2.0; p = .006). CONCLUSIONS: The HRQOL in chronic hepatitis C is not
      determined by the severity of the liver disease but by psychiatric and medical
      comorbidities and disease-related worries.

PMID- 15564365
TI  - Psychological factors in postoperative fatigue.
AB  - OBJECTIVE: To assess whether the fatigue commonly reported by patients following
      surgery is partly a result of somatization and/or cognitive-behavioral factors.
      METHODS: One hundred eighty-three patients completed questionnaires before
      surgery and then 2 days, 3 weeks and 6 months afterward. Multiple regressions
      were used to assess which of the following factors were important in predicting
      self-reported postoperative fatigue, controlling for preoperative fatigue and for
      various demographic and surgical variables: negative mood, history of mood
      disorder, preoperative expectations of fatigue, preoperative worry or optimism
      about surgery, preoperative beliefs about the benefits of activity or rest, self
      reported postoperative activity, self-reported cardiovascular deconditioning, and
      availability of social support. RESULTS: Controlling for demographic and surgical
      variables and preoperative fatigue, postoperative fatigue showed significant
      associations with negative mood at each stage of follow-up (p < .001) and was
      significantly predicted by history of mood disorder at 2 days postoperatively (p
      = .02). Higher fatigue expectations were self-fulfilling at 3 weeks after surgery
      (p = .02), whereas preoperative belief in physical activity as being beneficial
      to recovery predicted reduced fatigue at 6 months (p < .001). Finally, self
      reported breathlessness after exercise, an indicator of cardiovascular
      deconditioning, was also significantly associated with greater fatigue at 6
      months (p = .02). CONCLUSION: The results indicate that psychological processes
      may well be relevant in the etiology of postoperative fatigue. In particular, the
      results relating to mood and expectations suggest that somatization may be
      particularly important in the first few weeks following surgery, whereas
      cognitive-behavioral factors and cardiovascular deconditioning may be more
      important in determining later-stage recovery.

PMID- 15564366
TI  - Intimate male partner violence impairs immune control over herpes simplex virus
      type 1 in physically and psychologically abused women.
AB  - OBJECTIVE: Intimate partner violence (IPV) against women is a worldwide problem
      and a cause of significant distress and threat to health. Studies have focused
      mainly on mental health, and few have considered the effect on physiological
      systems. The aim of this research was to determine whether IPV also compromises
      the immune system, as evidenced by a decrease in immune regulation over herpes
      simplex virus type 1 (HSV-1), the latent virus that causes cold sores. METHODS:
      Physically abused (N = 47) and psychologically abused women (N = 27) were
      compared with nonabused control women (N = 37). Information about
      sociodemographic characteristics, lifetime history of victimization, and mental
      health status (depression, anxiety, and posttraumatic stress disorder) was
      obtained through structured interviews. Salivary samples were collected on two
      occasions, and the capacity to neutralize live HSV-1 virus was tested with a
      bioassay. In addition, salivary levels of HSV-1-specific antibody and total IgA
      were determined by enzyme-linked immunosorbent assay. RESULTS: Physically abused
      women had the lowest virus neutralization, significantly below the other two
      groups, with the psychologically abused group intermediate. HSV-1-specific
      antibody also tended to be lower in physically abused women, but these values
      were not directly correlated with virus neutralization, suggesting that loss of
      other antiviral factors accounted for the reduced bioactivity. The effect of IPV
      on immune function was not mediated directly by mental health status. CONCLUSION:
      These findings confirm that the stressful disturbance associated with IPV has
      important physiological consequences, which could impair health by increasing the
      likelihood of viral reactivation and reducing the ability to suppress virus
      proliferation.

PMID- 15564367
TI  - Postponing death: another failure to replicate.

PMID- 15564368
TI  - Autonomic nervous system assessment throughout the wake-sleep cycle and stress.

PMID- 15564369
TI  - Postponing death: additional studies on mortality rates and symbolically
      meaningful dates.

PMID- 15564372
TI  - Biogenesis of small nuclear RNPs.

PMID- 15564373
TI  - Polarized sorting in epithelial cells: raft clustering and the biogenesis of the
      apical membrane.
AB  - Polarized cells establish and maintain functionally distinct surface domains by
      an elaborate sorting process, which ensures accurate delivery of biosynthetic
      cargo to different parts of the plasma membrane. This is particularly evident in
      polarized epithelial cells, which have been used as a model system for studies of
      sorting mechanisms. The clustering of lipid rafts through the oligomerization of
      raft components could be utilized for segregating apical from basolateral cargo
      and for the generation of intracellular transport carriers. Besides functioning
      in polarized sorting in differentiated cells, raft clustering might also play an
      important role in the biogenesis of apical membrane domains during development.

PMID- 15564374
TI  - AP-1 subunits: quarrel and harmony among siblings.
AB  - The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein
      dimers. It mediates gene regulation in response to a plethora of physiological
      and pathological stimuli, including cytokines, growth factors, stress signals,
      bacterial and viral infections, as well as oncogenic stimuli. Studies in
      genetically modified mice and cells have highlighted a crucial role for AP-1 in a
      variety of cellular events involved in normal development or neoplastic
      transformation causing cancer. However, emerging evidence indicates that the
      contribution of AP-1 to determination of cell fates critically depends on the
      relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality
      of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated
      regulation of processes such as proliferation, differentiation, apoptosis and
      transformation should be considered within the context of a complex dynamic
      network of signalling pathways and other nuclear factors that respond
      simultaneously.

PMID- 15564375
TI  - FRS2-dependent SRC activation is required for fibroblast growth factor receptor
      induced phosphorylation of Sprouty and suppression of ERK activity.
AB  - Activation of signalling by fibroblast growth factor receptor leads to
      phosphorylation of the signalling attenuator human Sprouty 2 (hSpry2) on residue
      Y55. This event requires the presence of the signalling adaptor fibroblast growth
      factor receptor substrate 2 (FRS2). The phosphorylation of hSpry2 is therefore
      mediated by an intermediate kinase. Using a SRC family kinase-specific inhibitor
      and mutant cells, we show that hSpry2 is a direct substrate for SRC family
      kinases, including SRC itself. Activation of SRC via fibroblast growth factor
      signalling is dependent upon FRS2 and fibroblast growth factor receptor kinase
      activity. SRC forms a complex with hSpry2 and this interaction is enhanced by
      hSpry2 phosphorylation. Phosphorylation of hSpry2 is required for hSpry2 to
      inhibit activation of the extracellular signal-regulated kinase pathway. These
      results show that recruitment of SRC to FRS2 leads to activation of signal
      attenuation pathways.

PMID- 15564376
TI  - Tau interaction with microtubules in vivo.
AB  - Tau is a major microtubule-associated protein which induces bundling and
      stabilization of axonal microtubules (MTs). To investigate the interaction of tau
      with MTs in living cells, we expressed GFP-tau fusion protein in cultured Xenopus
      embryo neurons and performed time-lapse imaging of tau-labeled MTs. Tau uniformly
      labeled individual MTs regardless of their assembly/disassembly status and
      location along the axon. Photobleaching experiments indicated that interaction of
      tau with MTs is very dynamic, with a half-time of fluorescence recovery of the
      order of 3 seconds. Treatment of cells with taxol, a drug that suppresses MT
      dynamics, rapidly induced detachment of tau from MTs. Although binding of tau to
      straight MTs was uniform, there was a heightened concentration of tau at the
      sites of high MT curvature. Our results suggest that dynamic interaction of tau
      with MTs may modify local mechanical properties of individual MTs and play a
      crucial role in the remodeling of the MT cytoskeleton during neuronal plasticity.

PMID- 15564377
TI  - Nuclear import of the BTB/POZ transcriptional regulator Kaiso.
AB  - Kaiso is a BTB/POZ transcription factor that functions in vitro as a
      transcriptional repressor of the matrix metalloproteinase gene matrilysin and the
      non-canonical Wnt signaling gene Wnt-11, and as an activator of the acetylcholine
      receptor-clustering gene rapsyn. Similar to other BTB/POZ proteins (e.g. Bcl-6,
      PLZF, HIC-1), endogenous Kaiso localizes predominantly to the nuclei of mammalian
      cells. To date, however, the mechanism of nuclear import for most POZ
      transcription factors, including Kaiso, remain unknown. Here, we report the
      identification and characterization of a highly basic nuclear localization signal
      (NLS) in Kaiso. The functionality of this NLS was verified by its ability to
      target a heterologous beta-galactosidase/green-fluorescent-protein fusion protein
      to nuclei. The mutation of one positively charged lysine to alanine in the NLS of
      full-length Kaiso significantly inhibited its nuclear localization in various
      cell types. In addition, wild-type Kaiso, but not NLS-defective Kaiso, interacted
      directly with the nuclear import receptor Importin-alpha2 both in vitro and in
      vivo. Finally, minimal promoter assays using a sequence-specific Kaiso-binding
      site fusion with luciferase as reporter demonstrated that the identified NLS was
      crucial for Kaiso-mediated transcriptional repression. The identification of a
      Kaiso NLS thus clarifies the mechanism by which Kaiso translocates to the nucleus
      to regulate transcription of genes with diverse roles in cell growth and
      development.

PMID- 15564378
TI  - Dynamic relocation of epigenetic chromatin markers reveals an active role of
      constitutive heterochromatin in the transition from proliferation to quiescence.
AB  - Quiescent lymphocytes have small nuclei, filled with masses of facultative
      heterochromatin. Upon receiving mitogenic signals, these cells undergo nuclear
      enlargement, chromatin decondensation, the reactivation of cell proliferation,
      and changes in the intranuclear positioning of key genes. We examined the levels
      and intranuclear localization of major histone modifications and non-histone
      heterochromatin proteins in quiescent and reactivated mouse spleen lymphocytes.
      Dramatic and selective changes in localization of two heterochromatin-associated
      proteins, the histone variant macroH2A and HP1alpha occurred during lymphocyte
      reactivation. Reciprocal changes in the locations of these two proteins were
      observed in activated lymphocytes and cultured mouse fibroblasts induced into
      quiescence. We also describe a new apocentric nuclear compartment with a unique
      set of histone modifications that occurs as a zone of chromatin surrounding
      centromeric heterochromatin in differentiated lymphocytes. It is within this zone
      that the most significant changes occur in the transition from proliferation to
      quiescence. Our results suggest that constitutive centromeric heterochromatin
      plays an active role in cell differentiation and reactivation.

PMID- 15564379
TI  - Inhibition of ryanodine receptor 1 in fast skeletal muscle fibers induces a fast
      to-slow muscle fiber type transition.
AB  - Skeletal muscle fiber type is regulated by innervation-induced cell signaling
      including calcium release mechanisms that lead to transcriptional activation of
      fiber type-specific genes. Avian fast pectoralis major (PM) and slow medial
      adductor (MA) muscles differentially control expression of the slow myosin heavy
      chain 2 (slow MyHC2) gene. We report here that slow MyHC2 gene expression in fast
      PM muscle fibers is repressed by endogenous activity of the ryanodine receptor 1
      (RyR1). Inhibition of RyR1 with ryanodine led to expression of the slow MyHC2
      gene in innervated PM muscle fibers in vitro. Administration of ryanodine to
      innervated PM muscle fibers also decreased protein kinase C (PKC) activity, the
      reduction of which is necessary for slow MyHC2 gene expression in both PM and MA
      muscle fibers. Furthermore, RyR1 inhibition increased slow MyHC2 promoter
      activity in innervated PM muscle fibers and enhanced transcriptional activities
      of nuclear factor of activated T cells (NFAT) and myocyte enhancer factor 2
      (MEF2), as well as their interactions with their respective binding sites of the
      slow MyHC2 promoter. These results indicate that RyR1 activity in innervated fast
      PM muscle fibers contributes to the cell type-specific repression of slow muscle
      specific genes.

PMID- 15564380
TI  - Protein 4.1R regulates interphase microtubule organization at the centrosome.
AB  - In human red blood cells, protein 4.1 (4.1R) stabilizes the spectrin-actin
      network and anchors it to the plasma membrane. To contribute to the
      characterization of functional roles of 4.1R in nonerythroid cells, we analysed
      the effect of ectopic expression of 4.1R isoforms on interphase microtubules in
      fibroblastic cells. We found that specific 4.1R isoforms disturbed the
      microtubule architecture but not the actin cytoskeleton. Biochemical
      sedimentation and/or confocal microscopy analyses showed that the pericentriolar
      components gamma-tubulin and pericentrin remained at centrosomes, whereas the
      distributions of proteins p150Glued and the dynein intermediate chain were
      altered. Remarkably, 4.1R was displaced from the centrosome. In microtubule
      depolymerizing-repolymerizing assays, 4.1R-transfected cells showed an ability to
      depolymerize and nucleate microtubules that was similar to that of untransfected
      cells; however, microtubules became disorganized soon after regrowth. In
      microtubule-depolymerized transfected cells and during the initial steps of
      microtubule regrowth, centrosomal 4.1R localized with gamma-tubulin but did not
      when microtubules became disorganized. To learn more about centrosomal 4.1R
      function, isolated centrosomes were examined by confocal microscopy, western blot
      and in vitro microtubule aster-assembly assays. The experiments showed that 4.1R
      was present in isolated centrosome preparations, that it remained in the center
      of in-vitro-assembled microtubule asters and that more asters were assembled by
      the addition of protein 4.1R fused to glutathione-S-transferase. Together, these
      results indicate that 4.1R plays a key role at the centrosome, contributing to
      the maintenance of a radial microtubule organization.

PMID- 15564381
TI  - PTEN regulates motility but not directionality during leukocyte chemotaxis.
AB  - The localization at opposite cell poles of phosphatidylinositol-3 kinases and
      PTEN (phosphatase and tensin homolog on chromosome 10) governs Dictyostelium
      chemotaxis. To study this model in mammalian cells, we analyzed the dynamic
      redistribution of green fluorescent protein (GFP)-tagged PTEN chimeras during
      chemotaxis. N- or C-terminus GFP-tagged PTEN was distributed homogeneously in the
      cytoplasm of chemotaxing PTEN-negative Jurkat cells and PTEN-positive HL60 cells.
      Moreover, we did not detect uropod accumulation of endogenous PTEN in
      chemoattractant-stimulated HL60 cells. Cell fractionation indicated that both
      endogenous and ectopically expressed PTEN were confined largely to the cytosol,
      and that chemoattractant stimulation did not alter this location. PTEN re
      expression in Jurkat cells or PTEN depletion by specific siRNA in HL60 cells did
      not affect cell gradient sensing; PTEN nonetheless modulated chemoattractant
      induced actin polymerization and the speed of cell movement. The results suggest
      a role for PTEN in regulating actin polymerization, but not directionality during
      mammalian cell chemotaxis.

PMID- 15564382
TI  - Fad24, a mammalian homolog of Noc3p, is a positive regulator in adipocyte
      differentiation.
AB  - Adipocyte differentiation is controlled by complex actions involving gene
      expression and signal transduction. From metaphase to anaphase, peroxisome
      proliferator-activated receptor gamma, the CCAAT/enhancer-binding protein family
      and sterol regulatory element-binding protein-1 are known to function as master
      regulators. However, the mechanism underlying the earliest step, which triggers
      the initiation of differentiation, remains unknown. In previous reports, we have
      isolated a number of genes, whose expression increases in the early stage of
      differentiation in the mouse 3T3-L1 preadipocyte cell line. Here we report the
      cloning of the full-length cDNA and characterization of an unknown gene isolated
      previously and named fad24 (factor for adipocyte differentiation 24). Fad24
      encodes a protein consisting of 807 amino acids. The deduced amino acid sequence
      was shown to have a basic leucine zipper motif and a NOC domain. Expression of
      fad24 was rapidly induced after stimulation with inducers. Furthermore,
      overexpression of fad24 in NIH-3T3 cells promoted adipogenesis in the presence of
      a ligand for peroxisome proliferator-activated receptor gamma. FAD24 localizes in
      the nucleus, especially within nuclear speckles. As the nuclear speckle functions
      as a nascent transcription and pre-mRNA splicing machinery, there is a
      possibility that FAD24 functions as one of the components for transcription
      and/or pre-mRNA splicing and positively regulates adipocyte differentiation.

PMID- 15564383
TI  - Distinct roles for multiple Src family kinases at fertilization.
AB  - Egg activation at fertilization requires the release of Ca2+ from the endoplasmic
      reticulum of the egg. Recent evidence indicates that Src family kinases (SFKs)
      function in the signaling pathway that initiates this Ca2+ release in the eggs of
      many deuterostomes. We have identified three SFKs expressed in starfish (Asterina
      miniata) eggs, designated AmSFK1, AmSFK2 and AmSFK3. Antibodies made against the
      unique domains of each AmSFK protein revealed that all three are expressed in
      eggs and localized primarily to the membrane fraction. Both AmSFK1 and AmSFK3
      (but not AmSFK2) are necessary for egg activation, as determined by injection of
      starfish oocytes with dominant-interfering Src homology 2 (SH2) domains, which
      specifically delay and reduce the initial release of Ca2+ at fertilization.
      AmSFK3 exhibits a very rapid and transient kinase activity in response to
      fertilization, peaking at 30 seconds post sperm addition. AmSFK1 kinase activity
      also increases transiently at fertilization, but peaks later, at 2 minutes. These
      results indicate that there are multiple SFKs present in starfish eggs with
      distinct, perhaps sequential, signaling roles.

PMID- 15564384
TI  - Increased expression of Drosophila Su(var)3-7 triggers Su(var)3-9-dependent
      heterochromatin formation.
AB  - The Su(var)3-7 protein is essential for fly viability, and several lines of
      evidence support its key importance in heterochromatin formation: it binds to
      pericentric heterochromatin, it potently suppresses variegation and it interacts
      with HP1. However, the mode of action of Su(var)3-7 is poorly understood. Here we
      investigate in vivo the consequences of increased Su(var)3-7 expression on fly
      viability and chromatin structure. A large excess of Su(var)3-7 induces
      lethality, whereas lower doses permit survival and cause spectacular changes in
      the morphology of polytene chromosomes in males, and to a lesser extent in
      females. The male X is always the most affected chromosome: it becomes highly
      condensed and shortened, and its characteristic banding pattern is modified. In
      addition, Su(var)3-7 was found over the complete length of all chromosomes. This
      event coincides with the appearance of heterochromatin markers such as histone
      H3K9 dimethylation and HP1 at many sites on autosomes and, more strikingly, on
      the male X chromosome. These two features are strictly dependent on the histone
      methyltransferase Su(var)3-9, whereas the generalised localisation of Su(var)3-7
      is not. These data provide evidence for a dose-dependent regulatory role of
      Su(var)3-7 in chromosome morphology and heterochromatin formation. Moreover they
      show that Su(var)3-7 expression is sufficient to induce Su(var)3-9-dependent
      ectopic heterochromatinisation and suggest a functional link between Su(var)3-7
      and the histone-methyltransferase Su(var)3-9.

PMID- 15564385
TI  - Dynamic targeting of microtubules by TPPP/p25 affects cell survival.
AB  - Recently we identified TPPP/p25 (tubulin polymerization promoting protein/p25) as
      a brain-specific unstructured protein that induced aberrant microtubule
      assemblies and ultrastructure in vitro and as a new marker for Parkinson's
      disease and other synucleopathies. In this paper the structural and functional
      consequences of TPPP/p25 are characterized to elucidate the relationship between
      the in vitro and the pathological phenomena. We show that at low expression
      levels EGFP-TPPP/p25 specifically colocalizes with the microtubule network of
      HeLa and NRK cells. We found that the colocalization was dynamic (tg=5 seconds by
      fluorescence recovery after photobleaching) and changed during the phases of
      mitosis. Time-lapse and immunofluorescence experiments revealed that high levels
      of EGFP-TPPP/p25 inhibited cell division and promoted cell death. At high
      expression levels or in the presence of proteosome inhibitor, green fusion
      protein accumulated around centrosomes forming an aggresome-like structure
      protruding into the nucleus or a filamentous cage of microtubules surrounding the
      nucleus. These structures showed high resistance to vinblastin. We propose that a
      potential function of TPPP/p25 is the stabilization of physiological microtubular
      ultrastructures, however, its upregulation may directly or indirectly initiate
      the formation of aberrant protein aggregates such as pathological inclusions.

PMID- 15564386
TI  - Breast core-needle biopsy: clinical trial of relaxation technique versus
      medication versus no intervention for anxiety reduction.
AB  - PURPOSE: To evaluate effectiveness of oral anxiolytic medication versus
      relaxation technique for anxiety reduction in women undergoing breast core-needle
      biopsy (CNB). MATERIALS AND METHODS: The institutional review board reviewed and
      approved the study. Informed consent was obtained from 143 consecutive women
      scheduled for breast CNB. Women were randomized as follows: no anxiety
      intervention (usual care group), relaxation therapy with an audiotape of
      classical music and ocean sounds during CNB (relaxation group), and 0.5-mg of
      alprazolam administered orally 15 minutes before CNB (medication group). Anxiety
      before, during, and 24 hours after the procedure was assessed with State-Trait
      Anxiety Inventory and self-reported visual analog scale from 0 (no anxiety) to 10
      (worst anxiety). Data analysis was performed with statistical software.
      Descriptive statistics were computed for all variables. Group differences were
      determined with analysis of variance. Differences in mean values were assessed
      with Bonferroni multiple comparison procedure. Categorical demographic
      differences were assessed with chi(2) statistic. RESULTS: Preprocedural State
      Trait Anxiety Inventory scores indicated that women were not inherently anxious:
      usual care group, score of 44.63; relaxation group, 45.74; and medication group,
      49.1. Scores represented significantly elevated anxiety for women in all three
      groups when compared with the normative value of 35.12 (P < .0001), with no
      statistically significant differences between the scores of the three groups.
      Women in medication group reported significant reductions in anxiety (-44%) from
      levels determined before the procedure to levels determined during the procedure
      (P = .02) and significant reduction during the procedure when compared with
      changes in usual care (+15%) and relaxation (-8%) groups (P = .02). Women in all
      three groups reported significant reduction in anxiety from levels determined
      before the procedure to levels determined at 24 hours after it (P < .0001). There
      was no significant difference (P = .95) in 24-hour postprocedural anxiety levels
      among the three groups. CONCLUSION: Use of oral anxiolytic medication before
      breast CNB can significantly reduce anxiety women experience during the
      procedure.

PMID- 15564387
TI  - Effect of proteoglycan depletion on T2 mapping in rat patellar cartilage.
AB  - PURPOSE: To evaluate experimentally the sensitivity of T2 mapping with magnetic
      resonance (MR) imaging at 8.5 T in depicting variations in proteoglycan content
      and concurrent extracellular matrix of rat patellar cartilage. MATERIALS AND
      METHODS: The study was performed in 36 immature (age, 5 weeks) and 36 mature
      (age, 10 weeks) Wistar rats. Maintenance and care of the rats were conducted in
      accordance with National Institutes of Health guidelines. Fifty-six rats
      underwent T2 mapping in 28 right patellae degraded with hyaluronidase for 1 and 6
      hours and in 28 undegraded age-matched patellae that served as controls. After MR
      mapping, the rats were sacrificed, and the patellae were studied histologically
      to evaluate proteoglycan and collagen content and collagen network organization
      in cartilage. Biochemical analysis was performed in 88 patellae to quantify
      sulfated glycosaminoglycan and hydroxyproline content. Effects of age and/or
      degree of degradation were evaluated after rank transformation of continuous data
      by using rank analysis of variance (ANOVA). Associations between continuous
      variables were assessed with the Spearman rank correlation coefficient. RESULTS:
      Results of histologic analysis showed proteoglycan loss after hyaluronidase
      degradation without alteration of collagen network. No significant variation in
      hydroxyproline sulfate content was observed with depletion of proteoglycan.
      Proteoglycan losses of 19% and 13%, found after 1-hour degradation in immature
      and mature groups, respectively, were associated with significantly increased
      global T2 values (ANOVA, P < .001). Six-hour degradation resulted in more severe
      proteoglycan losses of 45% and 53% in immature and mature groups, respectively,
      inducing significant increases in global T2 values in immature and mature groups
      (ANOVA, P < .001). Variations in T2 values between superficial and deep cartilage
      zones were not affected by proteoglycan depletion. CONCLUSION: In rat patellar
      cartilage, T2 mapping permits detection of slight or severe proteoglycan
      depletion and concurrent changes of extracellular matrix when age-matched samples
      are compared.

PMID- 15564388
TI  - Large infiltrative hepatocellular carcinomas: treatment with percutaneous
      intraarterial ethanol injection alone or in combination with conventional
      percutaneous ethanol injection.
AB  - PURPOSE: To retrospectively evaluate patients' tolerance and the effectiveness of
      percutaneous intraarterial ethanol injection (PIAEI), alone or combined with
      conventional percutaneous ethanol injection (PEI), for treatment of advanced
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Neither institutional
      review board approval nor informed consent was required for this retrospective
      study; however, all patients had given their consent to be treated with PIAEI.
      Fourteen men and four women with cirrhosis and HCC who were ineligible for
      conventional curative treatment (largest tumor diameter, 35-90 mm; mean, 52 mm +/
      16 [standard deviation]) and whose supplying arteries were visible on computed
      tomographic (CT) and color Doppler ultrasonographic (US) images were treated with
      US-guided PIAEI-either alone or combined with PEI. Twelve patients had
      infiltrative tumors, and six had nodular tumors. Four patients had portal venous
      tumor involvement. Tumor necrosis and recurrence were evaluated with CT, and 1-
      and 2-year survival rates were evaluated with Kaplan-Meier analysis. RESULTS: In
      four patients, the main tumor was treated with PIAEI only, and in 14 patients,
      the main tumor was treated with combined PIAEI and PEI. One patient died of
      myocardial infarction before CT evaluation. Tumor necrosis was complete in 15
      (88%) and incomplete in two (12%) of 17 patients. Results of subsequent surgery
      performed in three patients confirmed the radiologic findings: complete tumor
      necrosis in two patients and incomplete necrosis in one patient. Two severe PIAEI
      related complications occurred: liver abscess, which resolved, and fatal acute
      pancreatitis. During the follow-up period (mean, 15 months +/- 6.7), six patients
      died owing to recurrent HCC, and 10 patients were alive with no detectable tumor
      after a mean follow-up period of 18 months +/- 11. One- and 2-year survival rates
      were 76.6% and 44.5%, respectively. CONCLUSION: For patients with advanced HCC
      who are ineligible for other curative options, PIAEI could be an effective
      treatment, despite the associated risk of severe complications.

PMID- 15564389
TI  - MR imaging evaluation of the postoperative knee.
AB  - The increased number of patients undergoing arthroscopy or surgery of the knee
      for sports medicine injuries is leading to increased numbers of patients who
      require imaging after surgery because of failure to improve, recurrent symptoms,
      or new injury. As in preoperative patients, magnetic resonance (MR) imaging is
      the most valuable imaging method for postoperative evaluation of the knee.
      Surgical changes increase the difficulty of diagnosis of abnormalities in the
      knee with MR imaging. MR arthrography with direct intraarticular injection of
      contrast material can help improve evaluation of the postoperative meniscus and
      possibly help improve evaluation of anterior cruciate ligament grafts in patients
      after surgery. Recognition of the normal postoperative MR imaging appearance of
      the structures in the knee and of abnormalities is essential to accurate MR
      imaging evaluation of these patients.

PMID- 15564390
TI  - Unknown primary tumors: detection with dual-modality PET/CT--initial experience.
AB  - PURPOSE: To retrospectively evaluate fused positron emission tomography
      (PET)/computed tomography (CT) in depicting the primary lesion in cancer of an
      unknown primary tumor, compared with PET, CT, and PET and CT side-by-side
      evaluation. MATERIALS AND METHODS: Institutional review board approval and
      informed consent were obtained. Forty-five patients (26 men and 19 women) with
      metastatic cervical adenopathy (n = 18) or extracervical metastases (n = 27) of
      unknown primary tumor were included. The mean age of the patients was 57 years
      (range, 29-95 years). PET/CT imaging was performed in all patients 1 hour after
      administration of 350 MBq of fluorodeoxyglucose with a whole-body field of view.
      Contrast agents were administered orally and intravenously in all patients to
      ensure diagnostic CT data. PET/CT data sets were evaluated for the primary tumor,
      and imaging results were compared with those of CT, PET, and PET and CT side-by
      side evaluation. Differences in diagnostic performance were assessed by using the
      McNemar test with Bonferroni correction, which accounts for multiple comparisons.
      RESULTS: PET/CT depicted the primary tumor in 15 (33%) of 45 patients. In 30
      (67%) patients, the primary tumor site remained occult (P > .05). PET and CT side
      by-side evaluation depicted 13 (29%) of 45 tumors (P > .05). PET alone revealed
      the primary tumor in 11 (24%) of 45 patients (P > .05), while CT alone helped in
      the correct diagnosis in eight (18%) of 45 patients (P > .05). There were no
      significant differences between the diagnostic accuracies of PET/CT and the other
      imaging modalities. CONCLUSION: PET/CT was able to depict more primary tumors,
      though not significantly, than either of the other imaging modalities, but larger
      patient cohorts are required to finally judge its value for revealing the primary
      tumor site.

PMID- 15564391
TI  - Chronic plantar fasciitis: acute changes in the heel after extracorporeal high
      energy shock wave therapy--observations at MR imaging.
AB  - PURPOSE: To prospectively evaluate with magnetic resonance (MR) imaging the acute
      changes in the heel associated with extracorporeal shock wave therapy (ESWT).
      MATERIALS AND METHODS: Institutional clinical study review board approved the
      study, and informed consent was obtained. MR imaging was performed within 24
      hours before and after ESWT on 18 feet of 12 patients (eight women and four men;
      age range, 33-63 years; average, 49.9 years) with chronic plantar fasciitis. ESWT
      was applied to the most painful point on the plantar surface of the heel, with a
      total of 1500 shocks at 18 kV. The MR imaging protocol consisted of sagittal and
      coronal T1- and T2-weighted images with and without fat saturation. The images
      were reviewed to assess the post-ESWT changes in soft-tissue and bone marrow
      edema, the thickness of the proximal plantar fascia, and the presence of a heel
      spur. Paired t test was used for the statistical analysis. RESULTS: Soft-tissue
      edema, which was present in 16 (89%) of 18 heels before ESWT, had increased in
      severity in 12 (75%) heels after ESWT. Calcaneus bone marrow edema at the
      insertion site was observed in eight heels before ESWT. After ESWT, the extant of
      bone marrow edema had increased in one heel and had newly developed in another
      heel. The heel spur seen in nine (50%) feet was not affected by ESWT. In 17 (94%)
      heels, the proximal plantar fascia was abnormally thick, with thickness not
      significantly changed with use of ESWT (P > .05). CONCLUSION: Increase in soft
      tissue edema is the most common acute response associated with ESWT.

PMID- 15564392
TI  - Cervical spine fractures in patients 65 years and older: a clinical prediction
      rule for blunt trauma.
AB  - PURPOSE: To determine clinical predictors of cervical spine fracture in the
      elderly and to develop a clinical prediction rule to guide appropriate imaging in
      high-risk patients. MATERIALS AND METHODS: Institutional review board approval
      was received with waiver of informed consent. A retrospective case-control study
      was performed on blunt trauma patients 65 years and older with cervical spine
      fractures and on randomly selected control subjects without fracture. Potential
      predictors of fracture were evaluated through simple and multivariate logistic
      regression. Simple predictors were grouped into clinically similar composite
      variables and were analyzed with multivariate logistic regression and recursive
      partitioning. A clinical prediction rule was generated. The receiver operating
      characteristic curve was calculated and adjusted through bootstrap validation.
      Absolute cervical spine fracture probabilities were calculated by using Bayes
      theorem for all elderly patients and for patients who underwent computed
      tomography. Results were compared with a previous prediction rule for all adults.
      RESULTS: Composite predictors of fracture in the elderly included focal
      neurologic deficit (adjusted odds ratio, 17.7; 95% confidence interval [CI]: 3.8,
      83.4), severe head injury (odds ratio, 3.2; 95% CI: 1.5, 7.1), high-energy
      mechanism (odds ratio 6.7; 95% CI: 3.1, 14.8), and moderate-energy mechanism
      (odds ratio 3.3; 95% CI: 1.3, 8.3). The prediction rule stratified patients into
      risk groups with fracture probabilities ranging from 0.4% (95% CI: 0.1%, 1.3%) to
      24.2% (95% CI: 5.7%, 100%). CONCLUSION: Clinical factors can be used to stratify
      patients 65 years and older into risk groups with a wide range of probabilities
      of cervical spine fracture. Knowledge of cervical fracture risk can help guide
      appropriate imaging in high-risk patients.

PMID- 15564393
TI  - Liver segmentation in living liver transplant donors: comparison of semiautomatic
      and manual methods.
AB  - PURPOSE: To compare the accuracy and repeatability of a semiautomatic
      segmentation algorithm with those of manual segmentation for determining liver
      volume in living liver transplant donors at magnetic resonance (MR) imaging.
      MATERIALS AND METHODS: The institutional review board approved this retrospective
      study and waived the requirement for informed consent. The semiautomatic
      segmentation algorithm is based on geometric deformable models and the level-set
      technique. It entails (a) placing initialization circle(s) on each image section,
      (b) running the algorithm, (c) inspecting and possibly manually modifying the
      contours obtained with the segmentation algorithm, and (d) placing lines to
      separate the liver segments. For 18 living donors (eight men and 10 women; mean
      age, 34 years; age range, 25-46 years), two observers each performed two
      semiautomatic and two manual segmentations on contrast material-enhanced T1
      weighted MR images. Each measurement was timed. Actual graft weight was measured
      during surgery. The time needed for manual and that needed for semiautomatic
      segmentation were compared. Accuracy and repeatability were evaluated with the
      Bland-Altman method. RESULTS: Mean interaction time was reduced from 25 minutes
      with manual segmentation to 5 minutes with semiautomatic segmentation. The mean
      total time for the semiautomatic process was 7 minutes 20 seconds. Differences
      between the actual volume and the estimated volume ranged from -223 to +123 mL
      for manual segmentation and from -214 to +86 mL for semiautomatic segmentation.
      The 95% limits of agreement for the ratio of actual graft volume to estimated
      graft volume were 0.686 and 1.601 for semiautomatic segmentation and 0.651 and
      1.957 for manual segmentation. Semiautomatic segmentation improved estimation in
      15 of 18 cases. Inter- and intraobserver repeatability was higher with
      semiautomatic segmentation. CONCLUSION: Use of the semiautomatic segmentation
      algorithm substantially reduces the time needed for volumetric measurement of
      liver segments while improving both accuracy and repeatability.

PMID- 15564394
TI  - Intraoperative diffusion-tensor MR imaging: shifting of white matter tracts
      during neurosurgical procedures--initial experience.
AB  - PURPOSE: To prospectively evaluate the location of white matter tracts with
      diffusion-tensor imaging (DTI) during neurosurgical procedures. MATERIALS AND
      METHODS: Ethical committee approval and signed informed consent were obtained. A
      1.5-T magnetic resonance imager with an adapted rotating surgical table that is
      placed in a radiofrequency-shielded operating theater was used for pre- and
      intraoperative imaging. DTI was performed by applying an echo-planar imaging
      sequence with six diffusion directions in 38 patients (20 female patients, 18
      male patients; age range, 7-77 years; mean age, 45.6 years) who were undergoing
      surgery (35 craniotomy and three burr hole procedures). Color-encoded maps of
      fractional anisotropy were generated by depicting white matter tracts. A rigid
      registration algorithm was used to compare pre- and intraoperative images.
      RESULTS: Intraoperative DTI was technically feasible in all patients, and no
      major image distortions occurred in the areas of interest. Pre- and
      intraoperative color-encoded maps of fractional anisotropy could be registered;
      these maps depicted marked and highly variable shifting of white matter tracts
      during neurosurgical procedures. In the 27 patients who underwent brain tumor
      resection, white matter tract shifting ranged from an inward shift of 8 mm to an
      outward shift of 15 mm (mean shift +/- standard deviation, outward shift of 2.5
      mm +/- 5.8). In 16 (59%) of 27 patients, outward shifting was detected; in eight
      (30%), inward shifting was detected. In eight patients who underwent temporal
      lobe resections for drug-resistant epilepsy, shifting was only inward and ranged
      from 2 to 14 mm (9 mm +/- 3.3). In two of the three patients who underwent burr
      hole procedures, outward shifting occurred. CONCLUSION: Intraoperative DTI can
      depict shifting of major white matter tracts that is caused by surgical
      intervention.

PMID- 15564395
TI  - Lower extremity: low-dose contrast agent intraarterial MR angiography in patients
      -initial results.
AB  - Institutional review board approval and patient consent were obtained. A low-dose
      injection protocol for intraarterial three-dimensional (3D) gadolinium-enhanced
      magnetic resonance (MR) angiography was derived from femoral flow phantom studies
      and prospectively evaluated in patients with peripheral arterial occlusive
      disease (PAOD). All MR angiograms were obtained at 1.5 T with a T1-weighted
      gradient-echo sequence. MR angiograms of a gadolinium dilution series (0.8-200.0
      mmol/L) were acquired in a femoral phantom at different flow rates. Signal-to
      noise ratios (SNRs) above the 75% threshold of the measured maximum were
      considered optimal. The lowest optimal concentration was injected intraarterially
      in nine patients to obtain 3D MR angiograms of the thigh and calf station.
      Contrast-to-noise ratios (CNRs) were calculated for four arterial segments. The
      low optimal concentration of 50 mmol/L (20-mL bolus volume), about 5% of the
      total permissible dose, showed SNRs larger than the 75% threshold in the phantom
      study. In patients, this concentration led to high-spatial-resolution angiograms
      with mean CNRs of 70.0 +/- 14.5 (+/- standard deviation) for the superficial
      femoral artery and 47.5 +/- 13.4 at the infrapopliteal level. Low-dose contrast
      agent intraarterial 3D MR angiography showed high arterial enhancement, enabling
      assessment of lower extremity arteries in patients with PAOD and multiple
      injections--a crucial precondition for MR-guided endovascular interventions.

PMID- 15564396
TI  - Can MR imaging be used to track delivery of intravascularly administered stem
      cells?

PMID- 15564401
TI  - The emerging role of pay-for-performance contracting for health care services.

PMID- 15564402
TI  - Mammography screening can survive malpractice ... if radiologists take center
      stage and assume the role of educator.

PMID- 15564403
TI  - Be careful to not willingly suspend disbelief.

PMID- 15564405
TI  - Case 77: aggressive angiomyxoma.

PMID- 15564406
TI  - Prostate depiction at endorectal MR spectroscopic imaging: investigation of a
      standardized evaluation system.
AB  - PURPOSE: To investigate the accuracy and interobserver variability of a
      standardized evaluation system for endorectal three-dimensional (3D) magnetic
      resonance (MR) spectroscopic imaging of the prostate. MATERIALS AND METHODS: The
      human research committee approved the study, and all patients provided written
      informed consent. Endorectal MR imaging and MR spectroscopic imaging were
      performed in 37 patients before they underwent radical prostatectomy. For the 22
      patients with good or excellent MR spectroscopic imaging data, step-section
      histopathologic tumor maps were used to identify spectroscopic voxels of
      unequivocally benign (n = 306) or malignant (n = 81) peripheral zone tissue. Two
      independent spectroscopists, unaware of all other findings, scored the spectra of
      the selected voxels by using a scale of 1 (benign) to 5 (malignant) that was
      based on standardized metabolic criteria. Descriptive statistical, receiver
      operating characteristics (ROC), and kappa statistical analyses of the data
      obtained by both readers were performed by using two definitions of cancer: one
      based on a voxel score of 3-5 and the other based on a score of 4 or 5. RESULTS:
      The scoring system had good accuracy (74.2%-85.0%) in the differentiation between
      benign and malignant tissue voxels, with areas under the ROC curve of 0.89 for
      reader 1 and 0.87 for reader 2. Specificities of 84.6% and 89.3% were achieved
      when a voxel score of 4 or 5 was used to identify cancer, and sensitivities of
      90% and 93% were achieved when a score of 3-5 was used to identify cancer.
      Readers demonstrated excellent interobserver agreement (kappa values, 0.79 and
      0.80). CONCLUSION: The good accuracy and excellent interobserver agreement
      achieved by using the standardized five-point scale to interpret peripheral zone
      metabolism demonstrate the potential effectiveness of using metabolic information
      to identify prostate cancer, and the clinical usefulness of this system warrants
      testing in prospective clinical trials of MR imaging combined with MR
      spectroscopic imaging.

PMID- 15564407
TI  - Practice management performance indicators in academic radiology departments.
AB  - PURPOSE: To determine the management performance indicators most frequently
      utilized in academic radiology departments in the United States. MATERIALS AND
      METHODS: This investigation met the criteria for an exemption from institutional
      review board approval. A cross-sectional study in which a validated national
      survey was sent to members of the Society of Chairmen of Academic Radiology
      Departments (SCARD) was conducted. The survey was designed to examine the
      following six categories of 28 performance indicators: (a) general organization,
      (b) volume and productivity, (c) radiology reporting, (d) access to examinations,
      (e) customer satisfaction, and (f) finance. A total of 158 variables were
      included in the analysis. Summary statistics, the chi(2) test, rank correlation,
      multiple regression analysis, and analysis of variance were used. RESULTS: A
      response rate of 42% (55 of 132 SCARD members) was achieved. The mean number of
      performance indicators used by radiology departments was 16 +/- 6.35 (standard
      deviation). The most frequently utilized performance indicators were as follows:
      (a) productivity, in terms of examination volume (78% [43 departments]) and
      examination volume per modality (78% [43 departments]); (b) reporting, in terms
      of report turnaround (82% [45 departments]) and transcription time (71% [39
      departments]); (c) access, in terms of appointment access to magnetic resonance
      imaging (80% [44 departments]); (d) satisfaction, in terms of number of patient
      complaints (84% [46 departments]); and (e) finance, in terms of expenses (67% [37
      departments]). Regression analysis revealed that the numbers of performance
      indicators in each category were statistically significant in predicting the
      total number of performance indicators used (P < .001 for all). Numbers of
      productivity and financial indicators were moderately correlated (r = 0.51).
      However, there were no statistically significant correlations between the numbers
      of performance indicators used and hospital location, hospital size, or
      department size (P > .4 for all). CONCLUSION: Assessing departmental performance
      with a wide range of management indicators is not yet an established and
      standardized practice in academic radiology departments in the United States.
      Among all indicators, productivity indicators are the most frequently used.

PMID- 15564408
TI  - Metastatic colorectal carcinoma: cost-effectiveness of percutaneous
      radiofrequency ablation versus that of hepatic resection.
AB  - PURPOSE: To evaluate the relative cost-effectiveness of radiofrequency (RF)
      ablation and hepatic resection in patients with metachronous liver metastases
      from colorectal carcinoma (CRC) and compare the outcomes, cost, and cost
      effectiveness of a variety of treatment and follow-up strategies. MATERIALS AND
      METHODS: A state-transition decision model for evaluating the (societal) cost
      effectiveness of RF ablation and hepatic resection in patients with CRC liver
      metastases was developed. The model tracks the presence, number, size, location,
      growth, detection, and removal of up to 15 individual metastases in each patient.
      Survival, quality of life, and cost are predicted on the basis of disease extent.
      Imaging, ablation, and resection affect outcomes through detection and
      elimination of individual metastases. Several patient care strategies were
      developed and compared on the basis of cost, effectiveness, and incremental cost
      effectiveness (expressed as dollars per quality-adjusted life-year [QALY]).
      Extensive sensitivity analysis was performed to evaluate the impact of
      alternative scenarios and assumptions on results. RESULTS: A strategy permitting
      ablation of up to five metastases with computed tomographic (CT) follow-up every
      4 months resulted in a gain of 0.65 QALYs relative to a no-treat strategy, at an
      incremental cost of $2400 per QALY. Compared with this ablation strategy, a
      strategy permitting resection of up to four metastases, one repeat resection, and
      CT follow-up every 6 months resulted in an additional gain of 0.76 QALYs at an
      incremental cost of $24 300 per QALY. Across a range of model assumptions, more
      aggressive treatment strategies (ie, ablation or resection of more metastases,
      treatment of recurrent metastases, more frequent follow-up imaging) were superior
      to less aggressive strategies and had incremental cost-effectiveness ratios of
      less than $35 000 per QALY. Findings were insensitive to changes in most model
      parameters; however, results were somewhat sensitive to changes in size
      thresholds for RF ablation, the number of metastases present, and surgery and
      treatment costs. CONCLUSION: RF ablation is a cost-effective treatment option for
      patients with CRC liver metastases. However, in most scenarios, hepatic resection
      is more effective (in terms of QALYs gained) than RF ablation and has an
      incremental cost-effectiveness ratio of less than $35 000 per QALY.

PMID- 15564409
TI  - The Golden S sign.

PMID- 15564410
TI  - Suspected acute pulmonary embolism: evaluation with multi-detector row CT versus
      digital subtraction pulmonary arteriography.
AB  - PURPOSE: To determine diagnostic accuracy of four-channel multi-detector row
      computed tomography (CT) in emergency room and inpatient populations suspected of
      having acute pulmonary embolism (PE) who prospectively underwent both CT and
      pulmonary arteriography (PA). MATERIALS AND METHODS: Patients referred for PA to
      assess suspected PE were eligible. Institutional review board approval and
      written informed consent were obtained. All patients underwent CT and PA within a
      48-hour period. For CT, 4 x 2.5-mm collimation was used. Three readers
      independently evaluated each study for PE presence. PE status, vessel level, and
      lobar location were determined by means of majority rule, and interobserver
      agreement (kappa) was calculated for PE status, as assessed with each modality.
      Sensitivity and specificity of CT were calculated by using PA as the reference
      standard. Two radiologists later reviewed false-positive CT studies. RESULTS: The
      study group comprised 93 patients (median age, 56 years; range, 19-88 years).
      Sensitivity, specificity, and accuracy of CT were 100%, 89%, and 91%,
      respectively. kappa values were 0.71 and 0.83 for CT and PA, respectively, and
      were not significantly different between modalities. At PA, 18 patients (19%) had
      PE at 50 vessel levels (five main and/or interlobar, 24 segmental, and 21
      subsegmental), 17 (94%) of which had PE at multiple sites. At CT, 26 patients
      (28%) had PE at 71 vessel levels (24 main and/or interlobar, 33 segmental, and 14
      subsegmental). Twenty patients (77%) had PE at multiple sites. Review of eight
      false-positive CT studies showed an appearance highly suggestive of acute PE in
      three patients, chronic PE in one, and no PE in three; one study was
      inconclusive. CT better demonstrated large-level vessel involvement (P < .01),
      while PA better demonstrated small-level vessel involvement (P < .01).
      CONCLUSION: Multi-detector row CT has an accuracy of 91% in the depiction of
      suspected acute PE when conventional PA is used as the reference standard.

PMID- 15564411
TI  - Right ventricular function after pulmonary valve replacement in patients with
      tetralogy of Fallot.
AB  - PURPOSE: To assess the time course of right ventricular (RV) function improvement
      after pulmonary valve replacement (PVR) in patients 25.2 years +/- 7.0 after
      repair of tetralogy of Fallot. MATERIALS AND METHODS: The medical ethics
      committee approved this study, and informed consent was obtained. Cardiac
      magnetic resonance (MR) imaging was performed before, 7 months after, and 19
      months after PVR in 25 consecutive patients with tetralogy of Fallot with a 1.5-T
      MR imager. RV function was assessed with gradient-echo sequences in the short
      axis plane. Pulmonary flow was assessed with a velocity-encoded phase-contrast
      sequence. Paired t test was used to evaluate follow-up data. Independent samples
      t test was used to assess differences based on the presence of recurrent
      pulmonary regurgitation (PR). RESULTS: Mean indexed RV end-diastolic volume
      decreased from 166.9 mL/m(2) +/- 41.3 before PVR to 113.5 mL/m(2)+/- 35.7 (P <
      .001) at 7-month follow-up and 111.7 mL/m(2)+/- 41.1 (P = .46) at 19-month follow
      up. The RV ejection fraction was corrected for PR and improved from 25.0% +/- 7.7
      before surgery to 44.1% +/- 11.9 (P < .001) and 45.2% +/- 11.1 (P = .39), at 7-
      and 19-month follow-up, respectively. Recurrent PR after PVR was found in 11
      patients; 14 patients did not have recurrent PR. Total reduction of indexed RV
      end-diastolic volume at 19 months follow-up was more prominent in patients who
      did not have recurrent PR than in patients who did have recurrent PR (P < .05).
      Furthermore, improvement of RV ejection fraction corrected for regurgitation was
      more marked in patients who did not have recurrent PR than in patients who did
      have recurrent PR (P < .05). CONCLUSION: In patients with tetralogy of Fallot, RV
      function improves rapidly after PVR and is sustained at 19-month follow-up in
      most patients; however, recurrence of PR after PVR appears to reduce recovery of
      RV systolic function.

PMID- 15564412
TI  - Quantification of afferent vessels shows reduced brain vascular density in
      subjects with leukoaraiosis.
AB  - PURPOSE: To investigate vessel density changes with increasing age in three areas
      of the brain and to correlate these changes with leukoaraiosis (LA) on the basis
      of magnetic resonance (MR) images and location in deep white matter (WM).
      MATERIALS AND METHODS: Internal review board approval or informed consent from
      next of kin was not required. Brains of 21 subjects (mean age, 72.5 years; 12
      men, nine women) were evaluated at autopsy with MR imaging. The presence of LA
      was indicated by confluent or patchy areas of hyperintensity in deep WM.
      Microvascular density (percentage of vessel area divided by total area) in
      subjects with LA was measured with computerized morphometric analysis in LA
      lesions, healthy-appearing WM at MR imaging, and the cortex. These measurements
      were compared with each other and with measurements from corresponding areas in
      healthy subjects. Afferent vasculature was stained with alkaline phosphatase in
      celloidin sections. Hypotheses were tested with computation of a series of
      repeated-measures linear mixed models. RESULTS: Autopsy brains from 12 subjects
      with LA (mean age, 72 years; six men, six women) and nine subjects without LA
      (mean age, 73 years; six men, three women) were studied. Afferent microvascular
      density +/- standard deviation in LA lesions in deep WM (2.56% +/- 1.56) was
      significantly lower than that in corresponding deep WM of healthy subjects (3.20%
      +/- 1.82) (P = .018). Subjects with LA demonstrated decreased afferent vascular
      density at early ages in all three areas of the brain when compared with healthy
      subjects of the same age. CONCLUSION: Findings of decreased afferent vascular
      density in the area of LA and outside the lesion indicate that LA is a
      generalized cerebrovascular disease process rather than one confined to deep WM.

PMID- 15564413
TI  - Protective effect of smoking: misleading use of statistics.

PMID- 15564414
TI  - Endovascular irradiation after femoropopliteal angioplasty.

PMID- 15564415
TI  - Cerebral perfusion CT techniques.

PMID- 15564416
TI  - Breast: the forgotten organ.

PMID- 15564417
TI  - Notices of duplicate publication.

PMID- 15564419
TI  - Selection and optimisation of biventricular pacing: the role of echocardiography.
AB  - The quantification of ventricular dyssynchrony is a key factor in identifying
      patients with severe heart failure who may benefit from cardiac resynchronisation
      with biventricular pacing (BVP). Echocardiographic techniques appear to offer
      superior sensitivity and specificity than the ECG in selecting these patients.
      This paper reviews the scope of current echocardiographic techniques for guiding
      both patient selection and optimisation of device programming following
      implantation.

PMID- 15564420
TI  - Echocardiographic evaluation of cardiac dyssynchrony for predicting a favourable
      response to cardiac resynchronisation therapy.
AB  - Cardiac resynchronisation therapy (CRT) is an established therapy for patients
      with heart failure with wide QRS duration. Recent studies observed that
      assessment of systolic dyssynchrony is an important diagnostic tool as the
      treatment involves the re-coordination of regional wall contraction within the
      left ventricle. Therefore, the effectiveness of CRT depends heavily on whether
      systolic dyssynchrony is present before the treatment. Echocardiography is a
      useful tool for quantitative measurement of the severity of dyssynchrony in these
      patients before and after CRT. A number of echocardiographic tools have been
      developed during the past three years for such purpose, include M mode
      measurement of septal-to-posterior wall delay, tissue Doppler imaging for septal
      to-lateral wall delay, the measurement of standard deviation of peak contraction
      time over 12 left ventricular segments, delayed longitudinal contraction, and
      potentially three dimensional echocardiography. This review discusses the
      potential role of various echocardiographic techniques in the assessment of
      systolic dyssynchrony and their clinical applications.

PMID- 15564421
TI  - Cardiac resynchronisation therapy: when the drugs don't work.

PMID- 15564422
TI  - BSE procedure guidelines for the clinical application of stress echocardiography,
      recommendations for performance and interpretation of stress echocardiography: a
      report of the British Society of Echocardiography Policy Committee.

PMID- 15564424
TI  - Established and evolving indications for cardiac resynchronisation.
AB  - Randomised trials involving large number of patients have demonstrated the
      benefits of cardiac resynchronisation therapy (CRT) in patients with heart
      failure who have failed optimal medical treatment. Echocardiography plays an
      important role in defining dyssynchrony which is key to optimal patient
      selection. The electrocardiographic criteria for patient selection is
      supplemented by the finding of dyssynchrony on Doppler myocardial imaging, and
      echocardiography with Doppler myocardial imaging may eventually replace the
      electrocardiographic criteria for selection of patients who derive benefit from
      CRT.

PMID- 15564426
TI  - Disorders of the anterior visual pathways.

PMID- 15564427
TI  - Neuro-ophthalmology: examination and investigation.

PMID- 15564428
TI  - Neuro-ophthalmological syndromes for neurologists.

PMID- 15564429
TI  - Diplopia and eye movement disorders.

PMID- 15564430
TI  - Bedside neuro-otological examination and interpretation of commonly used
      investigations.

PMID- 15564431
TI  - Evaluation and management of the dizzy patient.

PMID- 15564432
TI  - Neuro-otological syndromes for the neurologist.

PMID- 15564433
TI  - Introduction: physiological cross talk: nonhemostatic physiological effects of
      hemostasis-related components.

PMID- 15564434
TI  - Unexpected role of plasminogen activator inhibitor 1 in cell adhesion and
      detachment.
AB  - Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor
      of plasminogen activation in vivo, and thus it is one of the main regulators of
      the fibrinolytic system. In this regard, individuals with elevated PAI-1 seem to
      have an increased risk for thrombotic disease, whereas those lacking the
      inhibitor develop a lifelong bleeding diathesis. Unexpectedly, recent
      observations demonstrate that cancer patients with high PAI-1 levels have a poor
      prognosis for survival. This correlation with metastatic disease may be related
      to the observation that high PAI-1 levels decrease the adhesive strength of cells
      for their substratum, and that this de-adhesive activity of PAI-1 is not related
      to its role as a protease inhibitor. Initial insights into potential mechanisms
      by which PAI-1 regulates the attachment, detachment, and migration of cells are
      addressed in this review.

PMID- 15564435
TI  - New functions for an old enzyme: nonhemostatic roles for tissue-type plasminogen
      activator in the central nervous system.
AB  - Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase
      that activates the zymogen plasminogen to the broad-specificity proteinase
      plasmin. Tissue-type plasminogen activator is found not only in the blood, where
      its primary function is as a thrombolytic enzyme, but also in the central nervous
      system (CNS), where it promotes events associated with synaptic plasticity and
      acts as a regulator of the permeability of the neurovascular unit. Tissue-type
      plasminogen activator has also been associated with pathological events in the
      CNS such as cerebral ischemia and seizures. Neuroserpin is an inhibitory serpin
      that reacts preferentially with tPA and is located in regions of the brain where
      either tPA message or tPA protein are also found, indicating that neuroserpin is
      the selective inhibitor of tPA in the CNS. There is a growing body of evidence
      demonstrating the participation of tPA in a number of physiological and
      pathological events in the CNS, as well as the role of neuroserpin as the natural
      regulator of tPA's activity in these processes. This review will focus on
      nonhemostatic roles of tPA in the CNS with emphasis on its newly described
      function as a regulator of permeability of the neurovascular unit and on the
      regulatory role of neuroserpin in these events.

PMID- 15564436
TI  - Fibrin(ogen)-alpha M beta 2 interactions regulate leukocyte function and innate
      immunity in vivo.
AB  - In addition to its well-characterized role in hemostasis, fibrin(ogen) has been
      proposed to be a central regulator of the inflammatory response. Multiple in
      vitro studies have demonstrated that this hemostatic factor can alter leukocyte
      function, including cell adhesion, migration, cytokine and chemokine expression,
      degranulation, and other specialized processes. One important link between
      fibrin(ogen) and leukocyte biology appears to be the integrin receptor
      alpha(M)beta(2)/Mac-1, which binds to immobilized fibrin(ogen) and regulates
      leukocyte activities. Although it is well established that fibrin(ogen) is a
      ligand for alpha(M)beta(2), the precise molecular determinants that govern this
      interaction are only now becoming clear. A novel line of mice expressing a mutant
      form of fibrinogen (Fib gamma(390-396A)) has revealed that gamma chain residues
      390-396 are important for the high-affinity engagement of fibrinogen by
      alpha(M)beta(2) and leukocyte function in vivo. Fibrinogen gamma(390-396A) failed
      to support alpha(M)beta(2)-mediated adhesion of primary neutrophils, monocytes,
      and macrophages, and mice expressing this fibrinogen variant were found to
      exhibit a major defect in the host inflammatory response following acute
      challenges. Most notably, Fib gamma(390-396A) mice display a profound impediment
      in Staphylococcus aureus elimination by leukocytes following intraperitoneal
      inoculation. These findings have positively established the physiological
      importance of fibrin(ogen) as a ligand for alpha(M)beta(2) and illustrate that
      the fibrin(ogen) gamma chain residues 390-396 constitute a critical feature of
      the alpha(M)beta(2) binding motif. Finally, the Fib gamma(390-396A) mice
      represent a valuable system for better defining the contribution of fibrin(ogen)
      to the inflammatory response in the absence of any confounding alteration in
      clotting function.

PMID- 15564437
TI  - Mammalian septin function in hemostasis and beyond.
AB  - Interest in the biology of mammalian septin proteins has undergone a birth in
      recent years. Originally identified as critical for yeast budding throughout the
      1970s, the septin family is now recognized to extend from yeast to humans and is
      associated with a variety of events ranging from cytokinesis to vesicle
      trafficking. An emerging theme for septins is their presence at sites where
      active membrane or cytoplasmic partitioning is occurring. Here, we briefly review
      the mammalian septin protein family and focus on a prototypic human and mouse
      septin, termed SEPT5, that is expressed in the brain, heart, and megakaryocytes.
      Work from neurobiology laboratories has linked SEPT5 to the exocytic complex of
      neurons, with implications that SEPT5 regulates neurotransmitter release.
      Striking similarities exist between neurotransmitter release and the platelet
      release reaction, which is a critical step in platelet response to vascular
      injury. Work from our laboratory has characterized the platelet phenotype from
      mice containing a targeted deletion of SEPT5. Most strikingly, platelets from
      SEPT5(null) animals aggregate and release granular contents in response to
      subthreshold levels of agonists. Thus, the characterization of a SEPT5-deficient
      mouse has linked SEPT5 to the platelet exocytic process and, as such, illustrates
      it as an important protein for regulating platelet function. Recent data suggest
      that platelets contain a wide repertoire of different septin proteins and
      assemble to form macromolecular septin complexes. The mouse platelet provides an
      experimental framework to define septin function in hemostasis, with implications
      for neurobiology and beyond.

PMID- 15564438
TI  - Nuclear remodeling and reprogramming in transgenic pig production.
AB  - The manufacture of pigs with modifications to specific chromosomal regions
      requires that the modification first be made in somatic cells. The modified cells
      can then be used as donors for nuclear transfer (NT) in an attempt to clone that
      cell into a newborn animal. Unfortunately the procedures are inefficient and
      sometimes lead to animals that are abnormal. The cause of these abnormalities is
      likely established during the first cell cycle after the NT. Either the donor
      cell was abnormal or the oocyte cytoplasm was unable to adequately remodel the
      donor nucleus such that it was structured similar to the pronucleus of a zygote.
      A better understanding of chromatin remodeling and subsequent developmental gene
      expression will provide clues as to how procedures can be modified to generate
      fertile animals more efficiently.

PMID- 15564439
TI  - Role of estrogens in adipocyte development and function.
AB  - Estrogen has historically been viewed as a major regulator of adipose tissue in
      adult females, but recent work has indicated that estrogen's role in adipose
      biology may be broader than initially appreciated and has also provided important
      insights into the mechanism of estrogen effects on adipose tissue. Estrogen has
      direct effects on adipocytes to inhibit lipogenesis and may also have direct
      effects on other cellular constituents of adipose tissue, as well as metabolic
      effects on other target organs that can regulate adipose tissue. Estrogen has
      central effects on food consumption and energy expenditure that contribute to its
      overall inhibitory effects on adipose deposition. Estrogen also plays an
      important role in regulating adipose deposition in males and recently has been
      shown to be an important factor in the determination of adipocyte number,
      indicating that it regulates key developmental events in adipogenesis. Although
      critical questions still remain in our understanding of the overall role of
      estrogen in adipose tissue, it is clear that estrogen plays a more important role
      in adipose tissue than originally realized and that it is a major regulator of
      adipose tissue in both sexes during development and adulthood.

PMID- 15564440
TI  - Mounting evidence for vitamin D as an environmental factor affecting autoimmune
      disease prevalence.
AB  - Low vitamin D status has been implicated in the etiology of autoimmune diseases
      such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes
      mellitus, and inflammatory bowel disease. The optimal level of vitamin D intake
      required to support optimal immune function is not known but is likely to be at
      least that required for healthy bones. Experimentally, vitamin D deficiency
      results in the increased incidence of autoimmune disease. Mechanistically, the
      data point to a role for vitamin D in the development of self-tolerance. The
      vitamin D hormone (1,25-dihydroxy vitamin D(3)) regulates T helper cell (Th1) and
      dendritic cell function while inducing regulatory T-cell function. The net result
      is a decrease in the Th1-driven autoimmune response and decreased severity of
      symptoms. This review discusses the accumulating evidence pointing to a link
      between vitamin D and autoimmunity. Increased vitamin D intakes might decrease
      the incidence and severity of autoimmune diseases and the rate of bone fracture.

PMID- 15564441
TI  - Reducing arginase activity via dietary manganese deficiency enhances endothelium
      dependent vasorelaxation of rat aorta.
AB  - L-Arginine is a common substrate for the enzymes arginase and nitric oxide
      synthase (NOS). Acute inhibition of arginase enzyme activity improves endothelium
      dependent vasorelaxation, presumably by increasing availability of substrate for
      NOS. Arginase is activated by manganese (Mn), and the consumption of a Mn
      deficient (Mn-) diet can result in low arginase activity. We hypothesize that
      endothelium-dependent vasorelaxation is greater in rats fed Mn- versus Mn
      sufficient (Mn+) diets. Newly weaned rats fed Mn+ diets (0.5 microg Mn/g; n = 12)
      versus Mn+ diets (45 microg Mn/g; n = 12) for 44 +/- 3 days had (i) lower liver
      and kidney Mn and arginase activity (P < or = 0.05), (ii) higher plasma L
      arginine (P < or = 0.05), (iii) similar plasma and urine nitrate + nitrite, and
      (iv) similar staining for endothelial nitric oxide synthase in thoracic aorta.
      Vascular reactivity of thoracic aorta (approximately 720 microm i.d.) and small
      coronary arteries (approximately 110 microm i.d.) was evaluated using wire
      myographs. Acetylcholine (ACh; 10(-8)-10(-4) M) produced greater (P < or = 0.05)
      vasorelaxation in thoracic aorta from Mn- rats (e.g., maximal percent relaxation,
      79 +/- 7%) versus Mn + rats (e.g., maximal percent relaxation, 54 +/- 9%) at 5 of
      7 evaluated doses. Tension produced by NOS inhibition using N(G) monomethyl-L
      arginine (L-NMMA; 10(-3) M) and vasorelaxation evoked by (i) arginase inhibition
      using difluoromethylornithine (DFMO; 10(-7) M), (ii) ACh (10(-8)-10(-4) M) in the
      presence of DFMO, and (iii) sodium nitroprusside (10(-9)-10(-4) M) were
      unaffected by diet. No differences existed between groups concerning these
      responses in small coronary arteries. These findings support our hypothesis that
      endothelium-dependent vasorelaxation is greater in aortic segments from rats that
      consume Mn- versus Mn+ diets; however, responses from small coronary arteries
      were unaffected.

PMID- 15564442
TI  - Acetaminophen in the hypoxic and reoxygenated guinea pig myocardium.
AB  - We investigated the effects of 0.35-mM acetaminophen and its vehicle on isolated,
      perfused guinea pig hearts made hypoxic and subsequently reoxygenated. Hearts
      were allowed 30 min postinstrumentation to reach baseline, steady-state values,
      and then were exposed to 6 min of hypoxia (5% O(2), 5% CO(2), balance N(2))
      followed by 36 min of reoxygenation (95% O(2), 5% CO(2)). We recorded
      hemodynamic, metabolic, and mechanical data in addition to assessing
      ultrastructure and the capacity of coronary venous effluent to reduce reactive
      oxygen species. We found that acetaminophen-treated hearts retained a greater
      fraction of mechanical function during hypoxia and reoxygenation. For example,
      the average percentage change from baseline of left ventricular developed
      pressure in acetaminophen- and vehicle-treated hearts at 6 min reoxygenation was
      9 +/- 2% and -8 +/- 5% (P < 0.05), respectively. In addition, electron
      micrographs revealed greater preservation of myofibrillar ultrastructure in
      acetaminophen-treated hearts. Biochemical analyses revealed the potential of
      coronary effluent from acetaminophen-treated hearts to significantly neutralize
      peroxynitrite-dependent chemiluminescence in all recorded time periods. During
      early reoxygenation, the percentage inhibition of peroxynitrite-mediated
      chemiluminescence was 56 +/- 10% in vehicle-treated hearts and 99 +/- 1% in
      acetaminophen-treated hearts (P < 0.05). We conclude that acetaminophen has
      previously unreported cardioprotective properties in the nonischemic, hypoxic,
      and reoxygenated myocardium mediated through the reduction of reactive oxygen
      species.

PMID- 15564443
TI  - Hypoxic rise in cytosolic calcium and renal proximal tubule injury mediated by a
      nickel-sensitive pathway.
AB  - In the kidney, cell injury resulting from ischemia and hypoxia is thought to be
      due, in part, to increased cytosolic Ca(2+) levels, [Ca(2+)]i, leading to
      activation of lytic enzymes, cell dysfunction, and necrosis. We report evidence
      of a progressive and exponential increase in [Ca(2+)]i (from 245 +/- 10 to 975 +/
      100 nM at 45 mins), cell permeabilization and propidium iodide (PI) staining of
      the nucleus, and partial loss of cell transport functions such as Na(+)-gradient
      dependent uptakes of (14)C-alpha-methylglucopyranoside and inorganic phosphate
      ((32)Pi) in proximal convoluted tubules of adult rabbits subjected to hypoxia.
      The rise in [Ca(2+)]i depended on the presence of extracellular [Ca(2+)] and
      could be blocked by 50 microM Ni(2+)but not by verapamil (100 microM). Presence
      of 50 microM Ni(2+) also reduced the hypoxia-induced morphological and functional
      injuries. We also used HEK 293 cells, a kidney cell line, incubated in media
      without glucose and exposed for 3.5 hrs to 1% O(2)-5% CO(2) and then returned to
      glucose-containing media for another 3.5 hrs in an air-5% CO(2) atmosphere and
      finally exposed for 1 min to media containing 1 microM PI. NiCl(2) (50 microM) or
      pentobarbital (300 microM) more than phenobarbital (1.5 mM), when present in the
      incubation medium during both the hypoxic and the reoxygenation periods, induced
      significant (P < 0.001) reductions in the number of cell nuclei stained with PI,
      similar to their relative potency as inhibitors of T channels. Our findings
      indicate that hypoxia-induced alterations in calcium level and subsequent cell
      injury in the proximal convoluted tubule and in HEK cells involve a nickel
      sensitive and dihydropyridine insensitive pathway or channel.

PMID- 15564444
TI  - Alpha-TEA plus cisplatin reduces human cisplatin-resistant ovarian cancer cell
      tumor burden and metastasis.
AB  - A novel nonhydrolyzable ether-linked acetic acid analog of vitamin E, 2,5,7,8
      tetramethyl-2R-(4R,8R,12-trimethyltridecyl)-chroman-6-yloxyacetic acid (alpha
      TEA) in combination with cisplatin, reduces tumor burden of A2780/cp70 (cp70)
      cisplatin-resistant human ovarian cancer cells xenografted into immune
      compromised nude mice. Two xenograft studies were conducted using cp70 cells
      stably expressing green fluorescent protein (cp70-GFP) subcutaneously
      transplanted into NU/NU mice. For studies 1 and 2, alpha-TEA was formulated in
      liposomes and delivered by aerosol such that approximately 36 microg and 72
      microg of alpha-TEA were deposited in the respiratory tract of each mouse each
      day, respectively. Cisplatin at 5 mg/kg was administered by intraperitoneal
      injections once weekly for the first 3 weeks in Study 1 and on the third and 10th
      days following treatment initiation in Study 2. The combination alpha-TEA +
      cisplatin treatment reduced tumor burden and metastasis of cp70-GFP cells in
      comparison to control mice or mice treated with alpha-TEA or cisplatin singly. A
      significant reduction (P < 0.001) in growth of subcutaneous transplanted tumors
      was obtained with alpha-TEA + cisplatin for both studies. Visible metastases were
      observed in the lungs of animals from control and cisplatin-treated groups but
      not in animals from the alpha-TEA- or alpha-TEA + cisplatin-treated groups. The
      alpha-TEA + cisplatin significantly reduced the total number of lung and axillary
      lymph node micrometastasis (P < 0.03 and P < 0.0001, respectively). Analyses of
      tumor sections showed the alpha-TEA + cisplatin treatment group, in comparison to
      control, to have a significantly lower level of cell proliferation (Ki-67
      staining; P < 0.0001) and a significantly higher level of apoptosis (terminal
      deoxynucleotidyl transferase-mediated nick end labeling [TUNEL]; P < 0.0001). In
      summary, combinations of alpha-TEA + cisplatin significantly reduced tumor burden
      and metastases in a xenograft model of cisplatin-resistant human ovarian cancer
      cells. These data show promise for combination alpha-TEA + cisplatin chemotherapy
      for ovarian cancer.

PMID- 15564445
TI  - Prevention of spontaneous and experimentally induced diabetes in mice with zinc
      sulfate-enriched drinking water is associated with activation and reduction of NF
      kappa B and AP-1 in islets, respectively.
AB  - Recently, we reported that zinc sulfate-enriched (25 mM) drinking water (Zn(2+))
      protected male C57BL/6 mice from diabetes induced by multiple low doses of
      streptozotocin (MLD-STZ) and that MLD-STZ activates the transcription factors
      nuclear factor (NF)-kappa B and activator protein (AP)-1 in islets of these mice.
      Therefore, we studied the effect of Zn(2+) on spontaneous diabetes in female
      nonobese diabetic (NOD) mice and on the activity of NF-kappa B and AP-1 in islets
      of NOD and MLD-STZ-injected male C57BL/6 mice. We hypothesized that Zn(2+) may
      affect NF-kappa B, which may play a key role in immune-mediated diabetogenesis.
      Here we continuously administered Zn(2+) to NOD mice, to both parents and their
      F(1) offspring, and treated C57BL/6 male mice with MLD-STZ either alone or in
      addition to Zn(2+) . We assessed effects of Zn(2+) on insulitis and peri
      insulitis in 8-week-old NOD mice and analyzed NF-kappa B and AP-1 activities in
      islets. Zn(2+) significantly prevented diabetes in female F(1) offspring and
      significantly reduced insulitis and peri-insulitis. Zn(2+) significantly
      stimulated NF-kappa B and AP-1 activation in NOD mice, in contrast, in C57BL/6
      mice, Zn(2+) significantly reduced their activation by MLD-STZ. These data
      demonstrate that NF-kappa B may play a critical role in immune-mediated diabetes.
      Depending on the mode of beta-cell destruction, Zn(2+) may prevent apoptosis
      through activation of NF-kappa B in NOD mice or prevent inflammatory immune
      destruction through inhibition of NF-kappa B in MLD-STZ-treated C57BL/6 mice.

PMID- 15564446
TI  - Effects of iron and phytic acid on production of extracellular radicals by
      Enterococcus faecalis.
AB  - Enterococcus faecalis is a human intestinal commensal that produces extracellular
      superoxide, hydrogen peroxide, and hydroxyl radical while colonizing the
      intestinal tract. To determine whether dietary factors implicated in colorectal
      cancer affect oxidant production by E. faecalis, radicals were measured in rats
      colonized with this microorganism while on diets supplemented with iron or phytic
      acid. Hydroxyl radical activity was measured by assaying for aromatic
      hydroxylation products of D-phenylalanine using reverse-phase high-performance
      liquid chromatography and electrochemical detection. In vitro, as expected, iron
      enhanced, and phytic acid decreased, hydroxyl radical formation by E. faecalis.
      For rats colonized with E. faecalis given supplemental dietary iron (740 mg
      elemental iron as ferric phosphate per kg diet) or phytic acid (1.2% w/w), no
      differences were found in concentrations of urinary ortho- or meta- isomers of D
      phenylalanine compared to rats on a basal diet. Aqueous radicals in colonic
      contents were further assessed ex vivo by electron spin resonance using 5,5
      dimethyl-1-pyrroline-N-oxide as a spin trap. Mixtures of thiyl (sulfur-centered)
      and oxygen-centered radicals were detected across all diets. In vitro, similar
      spectra were observed when E. faecalis was incubated with hydrogen sulfide, air
      oxidized cysteine, or an alkylsulfide, as typical sulfur-containing compounds
      that might occur in colonic contents. In conclusion, intestinal colonization with
      E. faecalis in a rat model generates both thiyl and oxygen-centered radicals in
      colonic contents. Radical formation, however, was not significantly altered by
      short-term dietary supplementation with iron or phytic acid.

PMID- 15564447
TI  - Myocardial impairment in chronic hypoxia is abolished by short aeration episodes:
      involvement of K+ATP channels.
AB  - In vivo exposure to chronic hypoxia is considered to be a cause of myocardial
      dysfunction, thereby representing a deleterious condition, but repeated aeration
      episodes may exert some cardioprotection. We investigated the possible role of
      ATP-sensitive potassium channels in these mechanisms. First, rats (n = 8/group)
      were exposed for 14 days to either chronic hypoxia (CH; 10% O(2)) or chronic
      hypoxia with one episode/day of 1-hr normoxic aeration (CH+A), with normoxia (N)
      as the control. Second, isolated hearts were Langendorff perfused under hypoxia
      (10% O(2), 30 min) and reoxygenated (94% O(2), 30 min) with or without 3 microM
      glibenclamide (nonselective K(+)(ATP) channel-blocker) or 100 microM diazoxide
      (selective mitochondrial K(+)(ATP) channel-opener). Blood gasses, hemoglobin
      concentration, and plasma malondialdehyde were similar in CH and CH+A and in both
      different from normoxic (P < 0.01), body weight gain and plasma nitrate/nitrite
      were higher in CH+A than CH (P < 0.01), whereas apoptosis (number of TUNEL
      positive nuclei) was less in CH+A than CH (P < 0.05). During in vitro hypoxia,
      the efficiency (ratio of ATP production/pressure x rate product) was the same in
      all groups and diazoxide had no measurable effects on myocardial performance,
      whereas glibenclamide increased end-diastolic pressure more in N and CH than in
      CH+A hearts (P < 0.05). During reoxgenation, efficiency was markedly less in CH
      with respect to N and CH+A (P < 0.0001), and ratex pressure product remained
      lower in CH than N and CH+A hearts (P < 0.001), but glibenclamide or diazoxide
      abolished this difference. Glibenclamide, but not diazoxide, decreased vascular
      resistance in N and CH (P < 0.005 and < 0.001) without changes in CH+A. We
      hypothesize that cardioprotection in chronically hypoxic hearts derive from cell
      depolarization by sarcolemmal K(+)(ATP) blockade or from preservation of
      oxidative phosphorylation efficiency (ATP turnover/myocardial performance) by
      mitochondrial K(+)(ATP) opening. Therefore K(+)(ATP) channels are involved in the
      deleterious effects of chronic hypoxia and in the cardioprotection elicited when
      chronic hypoxia is interrupted with short normoxic aeration episodes.

PMID- 15564450
TI  - Identification of a naturally processed cytotoxic CD8 T-cell epitope of
      coxsackievirus B4, presented by HLA-A2.1 and located in the PEVKEK region of the
      P2C nonstructural protein.
AB  - The adaptive immune system generates CD8 cytotoxic T lymphocytes (CTLs) as a
      major component of the protective response against viruses. Knowledge regarding
      the nature of the peptide sequences presented by HLA class I molecules and
      recognized by CTLs is thus important for understanding host-pathogen
      interactions. In this study, we focused on identification of a CTL epitope
      generated from coxsackievirus B4 (CVB4), a member of the enterovirus group
      responsible for several inflammatory diseases in humans and often implicated in
      the triggering and/or acceleration of the autoimmune disease type 1 diabetes. We
      identified a 9-mer peptide epitope that can be generated from the P2C
      nonstructural protein of CVB4 (P2C(1137-1145)) and from whole virus by antigen
      presenting cells and presented by HLA-A2.1. This epitope is recognized by
      effector memory (gamma interferon [IFN-gamma]-producing) CD8 T cells in the
      peripheral blood at a frequency of responders that suggests that it is a major
      focus of the anti-CVB4 response. Short-term CD8 T-cell lines generated against
      P2C(1137-1145) are cytotoxic against peptide-loaded target cells. Of particular
      interest, the epitope lies within a region of viral homology with the diabetes
      related autoantigen, glutamic acid decarboxylase-65 (GAD(65)). However, P2C(1137
      1145)-specific cytotoxic T lymphocyte (CTL) lines were not activated to produce
      IFN-gamma by the GAD(65) peptide homologue and did not show cytotoxic activity in
      the presence of appropriately labeled targets. These results describe the first
      CD8 T-cell epitope of CVB4 that will prove useful in the study of CVB4-associated
      disease.

PMID- 15564451
TI  - Surface stability and immunogenicity of the human immunodeficiency virus envelope
      glycoprotein: role of the cytoplasmic domain.
AB  - The effects of two functional domains, the membrane-proximal YXXPhi motif and the
      membrane-distal inhibitory sequence in the long cytoplasmic tail of the human
      immunodeficiency virus type 1 (HIV-1) envelope protein (Env), on immunogenicity
      of the envelope protein were investigated. Genes with codons optimized for
      mammalian expression were synthesized for the HIV 89.6 Env and a truncated Env
      with 50 amino acids in the cytoplasmic domain to delete the membrane distal
      inhibitory sequence for surface expression. Additional genes were generated in
      which the tyrosine residue in the YXXPhi motif was changed into a serine. Pulse
      chase radioactive labeling and immunoprecipitation studies indicated that both
      domains can mediate endocytosis of the HIV Env, and removal of both domains is
      required to enhance HIV Env protein surface stability. Analysis of immune
      responses induced by DNA immunization of mice showed that the DNA construct for
      the mutant Env exhibiting enhanced surface stability induced significantly higher
      levels of antibody responses against the HIV Env protein. Our results suggest
      that the HIV Env cytoplasmic domain may play important roles in virus infection
      and pathogenesis by modulating its immunogenicity.

PMID- 15564452
TI  - Replicase-binding sites on plus- and minus-strand brome mosaic virus RNAs and
      their roles in RNA replication in plant cells.
AB  - The cis-acting elements for Brome mosaic virus (BMV) RNA synthesis have been
      characterized primarily for RNA3. To identify additional replicase-binding
      elements, nested fragments of all three of the BMV RNAs, both plus- and minus
      sense fragments, were constructed and tested for binding enriched BMV replicase
      in a template competition assay. Ten RNA fragments containing replicase-binding
      sites were identified; eight were characterized further because they were more
      effective competitors. All eight mapped to noncoding regions of BMV RNAs, and the
      positions of seven localized to sequences containing previously characterized
      core promoter elements (C. C. Kao, Mol. Plant Pathol. 3:55-62, 2001), thus
      suggesting the identities of the replicase-binding sites. Three contained the
      tRNA-like structures that direct minus-strand RNA synthesis, three were within
      the 3' region of each minus-strand RNA that contained the core promoter for
      genomic plus-strand initiation, and one was in the core subgenomic promoter.
      Single-nucleotide mutations known previously to abolish RNA synthesis in vitro
      prevented replicase binding. When tested in the context of the respective full
      length RNAs, the same mutations abolished BMV RNA synthesis in transfected barley
      protoplasts. The eighth site was within the intercistronic region (ICR) of plus
      strand RNA3. Further mapping showed that a sequence of 22 consecutive adenylates
      was responsible for binding the replicase, with 16 being the minimal required
      length. Deletion of the poly(A) sequence was previously shown to severely
      debilitate BMV RNA replication in plants (E. Smirnyagina, Y. H. Hsu, N. Chua, and
      P. Ahlquist, Virology 198:427-436, 1994). Interestingly, the B box motif in the
      ICR of RNA3, which has previously been determined to bind the 1a protein, does
      not bind the replicase. These results identify the replicase-binding sites in all
      of the BMV RNAs and suggest that the recognition of RNA3 is different from that
      of RNA1 and RNA2.

PMID- 15564453
TI  - Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup
      a infection and identify a fusion intermediate.
AB  - Fusion proteins of enveloped viruses categorized as class I are typified by two
      distinct heptad repeat domains within the transmembrane subunit. These repeats
      are important structural elements that assemble into the six-helix bundles
      characteristic of the fusion-activated envelope trimer. Peptides derived from
      these domains can be potent and specific inhibitors of membrane fusion and virus
      infection. To facilitate our understanding of retroviral entry, peptides
      corresponding to the two heptad repeat domains of the avian sarcoma and leukosis
      virus subgroup A (ASLV-A) TM subunit of the envelope protein were characterized.
      Two peptides corresponding to the C-terminal heptad repeat (HR2), offset from one
      another by three residues, were effective inhibitors of infection, while two
      overlapping peptides derived from the N-terminal heptad repeat (HR1) were not.
      Analysis of envelope mutants containing substitutions within the HR1 domain
      revealed that a single amino acid change, L62A, significantly reduced sensitivity
      to peptide inhibition. Virus bound to cells at 4 degrees C became sensitive to
      peptide within the first 5 min of elevating the temperature to 37 degrees C and
      lost sensitivity to peptide after 15 to 30 min, consistent with a transient
      intermediate in which the peptide binding site is exposed. In cell-cell fusion
      experiments, peptide inhibitor sensitivity occurred prior to a fusion-enhancing
      low-pH pulse. Soluble receptor for ASLV-A induces a lipophilic character in the
      envelope which can be measured by stable liposome binding, and this activation
      was found to be unaffected by inhibitory HR2 peptide. Finally, receptor-triggered
      conformational changes in the TM subunit were also found to be unaffected by
      inhibitory peptide. These changes are marked by a dramatic shift in mobility on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, from a subunit of 37
      kDa to a complex of about 80 kDa. Biotinylated HR2 peptide bound specifically to
      the 80-kDa complex, demonstrating a surprisingly stable envelope conformation in
      which the HR2 binding site is exposed. These experiments support a model in which
      receptor interaction promotes formation of an envelope conformation in which the
      TM subunit is stably associated with its target membrane and is able to bind a C
      terminal peptide.

PMID- 15564454
TI  - Two amino acid mutations in the capsid protein of type 2 porcine circovirus
      (PCV2) enhanced PCV2 replication in vitro and attenuated the virus in vivo.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning
      multisystemic wasting syndrome (PMWS) in pigs. To identify potential genetic
      determinants for virulence and replication, we serially passaged a PCV2 isolate
      120 times in PK-15 cells. The viruses harvested at virus passages 1 (VP1) and 120
      (VP120) were biologically, genetically, and experimentally characterized. The
      PCV2 VP120 virus replicated in PK-15 cells to a titer similar to that of the PK
      15 cell line-derived nonpathogenic PCV1 but replicated more efficiently than PCV2
      VP1 with a difference of about 1 log unit in the titers. The complete genomic
      sequences of viruses at passages 0, 30, 60, 90, and 120 were determined. After
      120 passages, only two nucleotide mutations were identified in the entire genome,
      and both were located in the capsid gene: the mutations were located at
      nucleotide positions 328 (C328G) and 573 (A573C). The C328G mutation, in which a
      proline at position 110 of the capsid protein changed to an alanine (P110A),
      occurred at passage 30 and remained in the subsequent passages. The second
      mutation, A573C, resulting in a change from an arginine to a serine at position
      191 (R191S), appeared at passage 120. To experimentally characterize the VP120
      virus, 31 specific-pathogen-free pigs were randomly divided into three groups.
      Ten pigs in group 1 received phosphate-buffered saline as negative controls. Each
      pig in group 2 (11 pigs) was inoculated intramuscularly and intranasally with
      10(4.9) 50% tissue culture infective doses (TCID(50)) of PCV2 VP120. Each pig in
      group 3 (10 pigs) was similarly inoculated with 10(4.9) TCID(50) of PCV2 VP1.
      Viremia was detected in 9 of 10 pigs in the PCV2 VP1 group with a mean duration
      of 3 weeks, but in only 4 of 11 pigs in the PCV2 VP120 group with a mean duration
      of 1.6 weeks. The PCV2 genomic copy numbers in serum in the PCV2 VP1 group were
      significantly higher than those in the PCV2 VP120 group (P < 0.0001). Gross and
      histopathologic lesions in pigs inoculated with PCV2 VP1 were more severe than
      those inoculated with PCV2 VP120 at both day 21 and 42 necropsies (P = 0.0032 and
      P = 0.0274, respectively). Taken together, the results from this study indicated
      that the P110A and R191S mutations in the capsid of PCV2 enhanced the growth
      ability of PCV2 in vitro and attenuated the virus in vivo. This finding has
      important implications for PCV2 vaccine development.

PMID- 15564455
TI  - The positively charged termini of L2 minor capsid protein required for bovine
      papillomavirus infection function separately in nuclear import and DNA binding.
AB  - During the papillomavirus (PV) life cycle, the L2 minor capsid protein enters the
      nucleus twice: in the initial phase after entry of virions into cells and in the
      productive phase to mediate encapsidation of the newly replicated viral genome.
      Therefore, we investigated the interactions of the L2 protein of bovine PV type 1
      (BPV1) with the nuclear import machinery and the viral DNA. We found that BPV1 L2
      bound to the karyopherin alpha2 (Kap alpha2) adapter and formed a complex with
      Kap alpha2beta1 heterodimers. Previous data have shown that the positively
      charged termini of BPV1 L2 are required for BPV1 infection after the binding of
      the virions to the cell surface. We determined that these BPV1 L2 termini
      function as nuclear localization signals (NLSs). Both the N-terminal NLS (nNLS)
      and the C-terminal NLS (cNLS) interacted with Kap alpha2, formed a complex with
      Kap alpha2beta1 heterodimers, and mediated nuclear import via a Kap alpha2beta1
      pathway. Interestingly, the cNLS was also the major DNA binding site of BPV1 L2.
      Consistent with the promiscuous DNA encapsidation by BPV1 pseudovirions, this DNA
      binding occurred without nucleotide sequence specificity. Moreover, an L2 mutant
      encoding a scrambled version of the cNLS, which supports production of virions,
      rescued the DNA binding but not the Kap alpha2 interaction. These data support a
      model in which BPV1 L2 functions as an adapter between the viral DNA via the cNLS
      and the Kaps via the nNLS and facilitates nuclear import of the DNA during
      infection.

PMID- 15564456
TI  - Immunogenicity study of glycoprotein-deficient rabies virus expressing
      simian/human immunodeficiency virus SHIV89.6P envelope in a rhesus macaque.
AB  - Rabies virus (RV) has recently been developed as a novel vaccine candidate for
      human immunodeficiency virus type 1 (HIV-1). The RV glycoprotein (G) can be
      functionally replaced by HIV-1 envelope glycoprotein (Env) if the gp160
      cytoplasmic domain (CD) of HIV-1 Env is replaced by that of RV G. Here, we
      describe a pilot study of the in vivo replication and immunogenicity of an RV
      with a deletion of G (DeltaG) expressing a simian/human immunodeficiency virus
      SHIV(89.6P) Env ectodomain and transmembrane domain fused to the RV G CD (DeltaG
      89.6P-RVG) in a rhesus macaque. An animal vaccinated with DeltaG-89.6P-RVG
      developed SHIV(89.6P) virus-neutralizing antibodies and SHIV(89.6P)-specific
      cellular immune responses after challenge with SHIV(89.6P). There was no evidence
      of CD4(+) T-cell loss, and plasma viremia was controlled to undetectable levels
      by 6 weeks postchallenge and has remained suppressed out to 22 weeks
      postchallenge.

PMID- 15564457
TI  - Lytic cycle gene regulation of Epstein-Barr virus.
AB  - Episomal reporter plasmids containing the Epstein-Barr virus (EBV) oriP sequence
      stably transfected into Akata Burkitt's lymphoma cells were used to analyze EBV
      lytic cycle gene regulation. First, we found that the Zp promoter of EBV, but not
      the Rp promoter, can be activated in the absence of protein synthesis in these
      oriP plasmids, casting doubt on the immediate early status of Rp. An additional
      level of regulation of Zp was implied by analysis of a mutation of the ZV
      element. Second, our analysis of late lytic cycle promoters revealed that the
      correct relative timing, dependence on ori lyt in cis, and sensitivity to
      inhibitors of DNA replication were reconstituted on the oriP plasmids. Late
      promoter luciferase activity from oriP plasmids also incorporating replication
      competent ori lyt was phosphonoacetic acid sensitive, a hallmark of EBV late
      genes. A minimal ori lyt, which only replicates weakly, was sufficient to confer
      late timing of expression specifically on late promoters. Finally, deletion
      analysis of EBV late promoter sequences upstream of the transcription start site
      confirmed that sequences between -49 and +30 are sufficient for late gene
      expression, which is dependent on ori lyt in cis. However, the TATT version of
      the TATA box found in many late genes was not essential for late expression.

PMID- 15564458
TI  - Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and
      regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast
      transformation.
AB  - Latent membrane protein 1 (LMP1), the Epstein-Barr virus oncoprotein, activates
      NF-kappaB, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and c
      Jun N-terminal kinase signaling. To determine global transcriptional changes
      induced by LMP1 in epithelial cells, genomic analysis of C33A cells stably
      expressing LMP1 was performed. Relatively few genes were induced by LMP1.
      Expression of two members of the Id (inhibitor of differentiation) family of
      proteins, Id1 and Id3, was induced in the presence of LMP1 and confirmed by mRNA
      and protein in C33A and Rat-1 cells. In Rat-1 foci transformed by LMP1, Id1
      protein was also increased. Id proteins are known negative regulators of E-box
      proteins that positively regulate p16 and potentially other cyclin-dependent
      kinase inhibitors (cdki's). In LMP1-expressing Rat-1 cells, cdki p27 was
      specifically downregulated. Decreased p27 was correlated with increased levels of
      Cdk2 and increased levels of phosphorylated retinoblastoma protein. This study
      describes new properties of LMP1 that likely contribute to transformation and
      oncogenesis.

PMID- 15564459
TI  - Coxsackievirus B3 infection induces cyr61 activation via JNK to mediate cell
      death.
AB  - Coxsackievirus B3 (CVB3), an enterovirus in the Picornavirus family, is the most
      common human pathogen associated with myocarditis and idiopathic dilated
      cardiomyopathy. We found upregulation of the cysteine-rich protein gene (cyr61)
      after CVB3 infection in HeLa cells with a cDNA microarray approach, which is
      confirmed by Northern blot analysis. It is also revealed that the extracellular
      amount of Cyr61 protein was increased after CVB3 infection in HeLa cells. cyr61
      is an early-transcribed gene, and the Cyr61 protein is secreted into the
      extracellular matrix. Its function is related to cell adhesion, migration, and
      neuronal cell death. Here, we show that activation of the cyr61 promoter by CVB3
      infection is dependent on JNK activation induced by CVB3 replication and viral
      protein expression in infected cells. To explore the role of Cyr61 protein in
      infected HeLa cells, we transiently overexpressed cyr61 and infected HeLa cells
      with CVB3. This increased CVB3 growth in the cells and promoted host cell death
      by viral infection, whereas down-expression of cyr61 with short interfering RNA
      reduced CVB3 growth and showed resistance to cell death by CVB3 infection. In
      conclusion, we have demonstrated a new role for cyr61 in HeLa cells infected with
      CVB3, which is associated with the cell death induced by virus infection. These
      data thus expand our understanding of the physiological functions of cyr61 in
      virus-induced cell death and provide new insights into the cellular factors
      involved.

PMID- 15564460
TI  - Two different molecular defects in the Tva receptor gene explain the resistance
      of two tvar lines of chickens to infection by subgroup A avian sarcoma and
      leukosis viruses.
AB  - The subgroup A to E avian sarcoma and leukosis viruses (ASLVs) are highly related
      and are thought to have evolved from a common ancestor. These viruses use
      distinct cell surface proteins as receptors to gain entry into avian cells.
      Chickens have evolved resistance to infection by the ASLVs. We have identified
      the mutations responsible for the block to virus entry in chicken lines resistant
      to infection by subgroup A ASLVs [ASLV(A)]. The tva genetic locus determines the
      susceptibility of chicken cells to ASLV(A) viruses. In quail, the ASLV(A)
      susceptibility allele tva(s) encodes two forms of the Tva receptor; these
      proteins are translated from alternatively spliced mRNAs. The normal cellular
      function of the Tva receptor is unknown; however, the extracellular domain
      contains a 40-amino-acid, cysteine-rich region that is homologous to the ligand
      binding region of the low-density lipoprotein receptor (LDLR) proteins. The
      chicken tva(s) cDNAs had not yet been fully characterized; we cloned the chicken
      tva cDNAs from two lines of subgroup A-susceptible chickens, line H6 and line 0.
      Two types of chicken tva(s) cDNAs were obtained. These cDNAs encode a longer and
      shorter form of the Tva receptor homologous to the Tva forms in quail. Two
      different defects were identified in cDNAs cloned from two different ASLV(A)
      resistant inbred chickens, line C and line 7(2). Line C tva(r) contains a single
      base pair substitution, resulting in a cysteine-to-tryptophan change in the LDLR
      like region of Tva. This mutation drastically reduces the binding affinity of
      Tva(R) for the ASLV(A) envelope glycoproteins. Line 7(2) tva(r2) contains a 4-bp
      insertion in exon 1 that causes a change in the reading frame, which blocks
      expression of the Tva receptor.

PMID- 15564461
TI  - Assembly protein precursor (pUL80.5 homolog) of simian cytomegalovirus is
      phosphorylated at a glycogen synthase kinase 3 site and its downstream "priming"
      site: phosphorylation affects interactions of protein with itself and with major
      capsid protein.
AB  - Capsid assembly among the herpes-group viruses is coordinated by two related
      scaffolding proteins. In cytomegalovirus (CMV), the main scaffolding constituent
      is called the assembly protein precursor (pAP). Like its homologs in other
      herpesviruses, pAP is modified by proteolytic cleavage and phosphorylation.
      Cleavage is essential for capsid maturation and production of infectious virus,
      but the role of phosphorylation is undetermined. As a first step in evaluating
      the significance of this modification, we have identified the specific sites of
      phosphorylation in the simian CMV pAP. Two were established previously to be
      adjacent serines (Ser156 and Ser157) in a casein kinase II consensus sequence.
      The remaining two, identified here as Thr231 and Ser235, are within consensus
      sequences for glycogen synthase kinase 3 (GSK-3) and mitogen-activated protein
      kinase, respectively. Consistent with Thr231 being a GSK-3 substrate, its
      phosphorylation required a downstream "priming" phosphate (i.e., Ser235) and was
      reduced by a GSK-3-specific inhibitor. Phosphorylation of Ser235 converts pAP to
      an electrophoretically slower-mobility isoform, pAP*; subsequent phosphorylation
      of pAP* at Thr231 converts pAP* to a still-slower isoform, pAP**. The mobility
      shift to pAP* was mimicked by substituting an acidic amino acid for either Thr231
      or Ser235, but the shift to pAP** required that both positions be phosphorylated.
      Glu did not substitute for pSer235 in promoting phosphorylation of Thr231. We
      suggest that phosphorylation of Thr231 and Ser235 causes charge-driven
      conformational changes in pAP, and we demonstrate that preventing these
      modifications alters interactions of pAP with itself and with major capsid
      protein, suggesting a functional significance.

PMID- 15564462
TI  - Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001.
AB  - In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was
      isolated from three acute flaccid paralysis patients and one contact from three
      separate communities in the Philippines. Complete genomic sequencing of these
      four cVDPV isolates revealed that the capsid region was derived from the Sabin 1
      vaccine strain but most of the noncapsid region was derived from an unidentified
      enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences
      of the cVDPV isolates were closely related to each other, and the isolates had a
      common recombination site. Most of the genetic and biological properties of the
      cVDPV isolates were indistinguishable from those of wild polioviruses. However,
      the most recently identified cVDPV isolate from a healthy contact retained the
      temperature sensitivity and partial attenuation phenotypes. The sequence
      relationships among the isolates and Sabin 1 suggested that cVDPV originated from
      an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain
      of transmission. Type 1 cVDPV was last detected in the Philippines in September
      2001, and population immunity to polio was raised by extensive OPV campaigns in
      late 2001 and early 2002.

PMID- 15564463
TI  - Coordination of transcription factor phosphorylation and histone methylation by
      the P-TEFb kinase during human immunodeficiency virus type 1 transcription.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein recruits positive
      transcription elongation factor b (P-TEFb) to the transactivation response (TAR)
      RNA structure to facilitate formation of processive transcription elongation
      complexes (TECs). Here we examine the role of the Tat/TAR-specified cyclin
      dependent kinase 9 (CDK9) kinase activity in regulation of HIV-1 transcription
      elongation and histone methylation. In HIV-1 TECs, P-TEFb phosphorylates the RNA
      polymerase II (RNAP II) carboxyl-terminal domain (CTD) and the transcription
      elongation factors SPT5 and Tat-SF1 in a Tat/TAR-dependent manner. Using in vivo
      chromatin immunoprecipitation analysis, we demonstrate the following distinct
      properties of the HIV-1 transcription complexes. First, the RNAP II CTD is
      phosphorylated at Ser 2 and Ser 5 near the promoter and at downstream coding
      regions. Second, the stable association of SPT5 with the TECs is dependent upon P
      TEFb kinase activity. Third, P-TEFb kinase activity is critical for the induction
      of methylation of histone H3 at lysine 4 and lysine 36 on HIV-1 genes.
      Flavopiridol, a potent P-TEFb kinase inhibitor, inhibits CTD phosphorylation,
      stable SPT5 binding, and histone methylation, suggesting that its potent
      antiviral activity is due to its ability to inhibit several critical and unique
      steps in HIV-1 transcription elongation.

PMID- 15564464
TI  - Insertion of a classical nuclear import signal into the matrix domain of the Rous
      sarcoma virus Gag protein interferes with virus replication.
AB  - The Rous sarcoma virus Gag protein undergoes transient nuclear trafficking during
      virus assembly. Nuclear import is mediated by a nuclear targeting sequence within
      the MA domain. To gain insight into the role of nuclear transport in replication,
      we investigated whether addition of a "classical " nuclear localization signal
      (NLS) in Gag would affect virus assembly or infectivity. A bipartite NLS derived
      from nucleoplasmin was inserted into a region of the MA domain of Gag that is
      dispensable for budding and infectivity. Gag proteins bearing the nucleoplasmin
      NLS insertion displayed an assembly defect. Mutant virus particles (RC.V8.NLS)
      were not infectious, although they were indistinguishable from wild-type virions
      in Gag, Gag-Pol, Env, and genomic RNA incorporation and Gag protein processing.
      Unexpectedly, postinfection viral DNA synthesis was also normal, as similar
      amounts of two-long-terminal-repeat junction molecules were detected for
      RC.V8.NLS and wild type, suggesting that the replication block occurred after
      nuclear entry of proviral DNA. Phenotypically revertant viruses arose after
      continued passage in culture, and sequence analysis revealed that the
      nucleoplasmin NLS coding sequence was deleted from the gag gene. To determine
      whether the nuclear targeting activity of the nucleoplasmin sequence was
      responsible for the infectivity defect, two critical basic amino acids in the NLS
      were altered. This virus (RC.V8.KR/AA) had restored infectivity, and the MA.KR/AA
      protein showed reduced nuclear localization, comparable to the wild-type MA
      protein. These data demonstrate that addition of a second NLS, which might direct
      MA and/or Gag into the nucleus by an alternate import pathway, is not compatible
      with productive virus infection.

PMID- 15564465
TI  - A conserved histidine in the ij loop of the Semliki Forest virus E1 protein plays
      an important role in membrane fusion.
AB  - The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH
      triggered membrane fusion reaction mediated by the E1 protein. E1 is a class II
      fusion protein that contains the hydrophobic fusion peptide loop and converts to
      a stable homotrimer during the fusion reaction. Intriguingly, the fusion loop is
      closely associated with a loop connecting the i and j beta-strands. This ij loop
      plays a role in the cholesterol dependence of membrane fusion and is specifically
      susceptible to proteolysis in the protease-resistant E1 homotrimer. The SFV ij
      loop contains a histidine residue at position 230. Sequence comparisons revealed
      that an analogous histidine is completely conserved in all alphavirus and
      flavivirus fusion proteins. An E1 H230A mutant was constructed using the SFV
      infectious clone. Although cells infected with H230A RNA produced virus
      particles, these virions were completely noninfectious and were blocked in both
      cell-cell fusion and lipid mixing assays. The H230A virions efficiently bound to
      cell surface receptors and responded to low pH by undergoing acid-dependent
      conformational changes including dissociation of the E1/E2 dimer, exposure of the
      fusion loop, association with target liposomes, exposure of acid-conformation
      specific epitopes, and formation of the stable E1 homotrimer. Studies with a
      soluble fragment of E1 showed that the mutant protein was defective in lipid
      dependent conformational changes. Our results indicate that the E1 ij loop and
      the conserved H230 residue play a critical role in alphavirus-membrane fusion and
      suggest the presence of a previously undescribed late intermediate in the fusion
      reaction.

PMID- 15564466
TI  - In vitro characterization of a simian immunodeficiency virus-human
      immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase
      to study antiviral resistance in pigtail macaques.
AB  - Antiviral resistance is a significant obstacle in the treatment of human
      immunodeficiency virus type 1 (HIV-1)-infected individuals. Because nonnucleoside
      reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse
      transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus
      (SIV) RT, the development of animal models to study the evolution of antiviral
      resistance has been problematic. To facilitate in vivo studies of NNRTI
      resistance, we examined whether a SIV that causes immunopathogenesis in pigtail
      macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency
      viruses (SHIVs) were derived from the genetic background of SIV(mne): SIV-RT-YY
      contains RT substitutions intended to confer NNRTI susceptibility (V181Y and
      L188Y), and RT-SHIV(mne) contains the entire HIV-1 RT coding region. Both mutant
      viruses grew to high titers in vitro but had reduced fitness relative to wild
      type SIV(mne). Although the HIV-1 RT was properly processed into p66 and p51
      subunits in RT-SHIV(mne) particles, the RT-SHIV(mne) virions had lower levels of
      RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT
      activity in RT-SHIV(mne) and SIV-RT-YY particles. HIV-1 and RT-SHIV(mne) were
      similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However,
      SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIV(mne). Classical
      NNRTI resistance mutations were selected in RT-SHIV(mne) after in vitro drug
      treatment and were monitored in a sensitive allele-specific real-time RT-PCR
      assay. Collectively, these results indicate that RT-SHIV(mne) may be a useful
      model in macaques for the preclinical evaluation of NNRTIs and for studies of the
      development of drug resistance in vivo.

PMID- 15564467
TI  - Role of the VP16-binding domain of vhs in viral growth, host shutoff activity,
      and pathogenesis.
AB  - The virion host shutoff (vhs) protein of herpes simplex virus type 1 causes the
      degradation of host and viral mRNA immediately upon infection of permissive
      cells. vhs can interact with VP16 through a 20-amino-acid binding domain, and
      viruses containing a deletion of this VP16-binding domain of vhs (Delta20) and a
      corresponding marker rescue (Delta20R) were constructed and characterized.
      Transient-transfection assays showed that this domain was dispensable for vhs
      activity. The Delta20 recombinant virus, however, was unable to induce mRNA
      degradation in the presence of actinomycin D, while degradation induced by
      Delta20R was equivalent to that for wild-type virus. Delta20, Delta20R, and KOS
      caused comparable RNA degradation in the absence of actinomycin D. Western blot
      analysis of infected cells indicated that comparable levels of vhs were expressed
      by Delta20, Delta20R, and KOS, and there was only a modest reduction of vhs
      packaging in Delta20. Immunoprecipitation of protein from cells infected with
      Delta20 and Delta20R showed equivalent coprecipitation of vhs and VP16.
      Pathogenesis studies with Delta20 showed a significant decrease in replication in
      the corneas, trigeminal ganglia, and brains, as well as a significant reduction
      in clinical disease and lethality, but no significant difference in the
      establishment of, or reactivation from, latency compared to results with KOS and
      Delta20R. These results suggest that the previously described VP16-binding domain
      is not required for vhs packaging or for binding to VP16. It is required,
      however, for RNA degradation activity of tegument-derived vhs and wild-type
      replication and virulence in mice.

PMID- 15564468
TI  - Furin-mediated cleavage of the feline foamy virus Env leader protein.
AB  - The molecular biology of spuma or foamy retroviruses is different from that of
      the other members of the Retroviridae. Among the distinguishing features, the N
      terminal domain of the foamy virus Env glycoprotein, the 16-kDa Env leader
      protein Elp, is a component of released, infectious virions and is required for
      particle budding. The transmembrane protein Elp specifically interacts with N
      terminal Gag sequences during morphogenesis. In this study, we investigate the
      mechanism of Elp release from the Env precursor protein. By a combination of
      genetic, biochemical, and biophysical methods, we show that the feline foamy
      virus (FFV) Elp is released by a cellular furin-like protease, most likely furin
      itself, generating an Elp protein consisting of 127 amino acid residues. The
      cleavage site fully conforms to the rules for an optimal furin site. Proteolytic
      processing at the furin cleavage site is required for full infectivity of FFV.
      However, utilization of other furin proteases and/or cleavage at a suboptimal
      signal peptidase cleavage site can partially rescue virus viability. In addition,
      we show that FFV Elp carries an N-linked oligosaccharide that is not conserved
      among the known foamy viruses.

PMID- 15564469
TI  - Efficient replication by herpes simplex virus type 1 involves activation of the
      IkappaB kinase-IkappaB-p65 pathway.
AB  - Infection by herpes simplex virus type 1 (HSV-1) induces a persistent nuclear
      translocation of NFkappaB. To identify upstream effectors of NFkappaB and their
      effect on virus replication, we employed mouse embryo fibroblast (MEF)-derived
      cell lines with deletions of either IKK1 or IKK2, the catalytic subunits of the
      IkappaB kinase (IKK) complex. Infected MEFs were assayed for virus yield, loss of
      IkappaBalpha, nuclear translocation of p65, and NFkappaB DNA-binding activity.
      Absence of either IKK1 or IKK2 resulted in an 86 to 94% loss of virus yield
      compared to that of normal MEFs, little or no loss of IkappaBalpha, and greatly
      reduced NFkappaB nuclear translocation. Consistent with reduced virus yield,
      accumulation of the late proteins VP16 and gC was severely depressed. Infection
      of normal MEFs, Hep2, or A549 cells with an adenovirus vector expressing a
      dominant-negative (DN) IkappaBalpha, followed by superinfection with HSV,
      resulted in a 98% drop in virus yield. These results indicate that the IKK
      IkappaB-p65 pathway activates NFkappaB after virus infection. Analysis of
      NFkappaB activation and virus replication in control and double-stranded RNA
      activated protein kinase-null MEFs indicated that this kinase plays no role in
      the NFkappaB activation pathway. Finally, in cells where NFkappaB was blocked
      because of DNIkappaB expression, HSV failed to suppress two markers of apoptosis,
      cell surface Annexin V staining and PARP cleavage. These results support a model
      in which activation of NFkappaB promotes efficient replication by HSV, at least
      in part by suppressing a host innate response to virus infection.

PMID- 15564470
TI  - Molecular characterization of human immunodeficiency virus type 1 and hepatitis C
      virus in paid blood donors and injection drug users in china.
AB  - China is facing a rapid upsurge in cases of human immunodeficiency virus type 1
      (HIV-1) and hepatitis C virus (HCV) infection due to large numbers of paid blood
      donors (PBD), injection drug users (IDU), and sexual partners of infected
      individuals. In this report, a total of 236 HIV-1-positive blood samples were
      collected from PBD, IDU, and their sexual partners in the most severely affected
      provinces, such as Henan, Yunnan, Guangxi, and Xinjiang. PCR was used to amplify
      the p17 region of gag and the C2-V3 region of env of HIV-1 and the 5' noncoding
      region and a region of E1/E2 of HCV. Genetic characterization of viral sequences
      indicated that there are two major epidemics of HIV-1 and multiple HCV epidemics
      in China. The PBD and transfusion recipients in Henan harbored HIV-1 subtype B',
      which is similar to the virus found in Thailand, and HCV genotypes 1b and 2a,
      whereas the IDU in Yunnan, Guangxi, and Xinjiang carried HIV-1 circulating
      recombinant forms 07 and 08, which resemble those in India, and HCV genotypes 1b,
      3a, and 3b. Our findings show that the epidemics of HIV-1 and HCV infection in
      China are the consequences of multiple introductions. The distinct distribution
      patterns of both the HIV-1 and HCV genotypes in the different high-risk groups
      are tightly linked to the mode of transmission rather than geographic proximity.
      These findings provide information relevant to antiviral therapy and vaccine
      development in China and should assist public health workers in implementing
      measures to reduce the further dissemination of these viruses in the world's most
      populous nation.

PMID- 15564471
TI  - Identification of severe acute respiratory syndrome coronavirus replicase
      products and characterization of papain-like protease activity.
AB  - Gene 1 of the coronavirus associated with severe acute respiratory syndrome
      (SARS) encodes replicase polyproteins that are predicted to be processed into 16
      nonstructural proteins (nsps 1 to 16) by two viral proteases, a papain-like
      protease (PLpro) and a 3C-like protease (3CLpro). Here, we identify SARS
      coronavirus amino-terminal replicase products nsp1, nsp2, and nsp3 and describe
      trans-cleavage assays that characterize the protease activity required to
      generate these products. We generated polyclonal antisera to glutathione S
      transferase-replicase fusion proteins and used the antisera to detect replicase
      intermediates and products in pulse-chase experiments. We found that nsp1 (p20)
      is rapidly processed from the replicase polyprotein. In contrast, processing at
      the nsp2/3 site is less efficient, since a approximately 300-kDa intermediate
      (NSP2-3) is detected, but ultimately nsp2 (p71) and nsp3 (p213) are generated. We
      found that SARS coronavirus replicase products can be detected by 4 h
      postinfection in the cytoplasm of infected cells and that nsps 1 to 3 colocalize
      with newly synthesized viral RNA in punctate, perinuclear sites consistent with
      their predicted role in viral RNA synthesis. To determine if PLpro is responsible
      for processing these products, we cloned and expressed the PLpro domain and the
      predicted substrates and established PLpro trans-cleavage assays. We found that
      the PLpro domain is sufficient for processing the predicted nsp1/2 and nsp2/3
      sites. Interestingly, expression of an extended region of PLpro that includes the
      downstream hydrophobic domain was required for processing at the predicted nsp3/4
      site. We found that the hydrophobic domain is inserted into membranes and that
      the lumenal domain is glycosylated at asparagine residues 2249 and 2252. Thus,
      the hydrophobic domain may anchor the replication complex to intracellular
      membranes. These studies revealed that PLpro can cleave in trans at the three
      predicted cleavage sites and that it requires membrane association to process the
      nsp3/4 cleavage site.

PMID- 15564472
TI  - Mucosal human papillomaviruses encode four different E5 proteins whose chemistry
      and phylogeny correlate with malignant or benign growth.
AB  - We performed a phylogenetic study of the E2-L2 region of human mucosal
      papillomaviruses (PVs) and of the proteins therein encoded. Hitherto, proteins
      codified in this region were known as E5 proteins. We show that many of these
      proteins could be spurious translations, according to phylogenetic and chemical
      coherence criteria between similar protein sequences. We show that there are four
      separate families of E5 proteins, with different characteristics of phylogeny,
      chemistry, and rate of evolution. For the sake of clarity, we propose a change in
      the present nomenclature. E5alpha is present in groups A5, A6, A7, A9, and A11,
      PVs highly associated with malignant carcinomas of the cervix and penis. E5beta
      is present in groups A2, A3, A4, and A12, i.e., viruses associated with certain
      warts. E5gamma is present in group A10, and E5delta is encoded in groups A1, A8,
      and A10, which are associated with benign transformations. The phylogenetic
      relationships between mucosal human PVs are the same when considering the
      oncoproteins E6 and E7 and the E5 proteins and differ from the phylogeny
      estimated for the structural proteins L1 and L2. Besides, the protein divergence
      rate is higher in early proteins than in late proteins, increasing in the order
      L1 < L2 < E6 approximately E7 < E5. Moreover, the same proteins have diverged
      more rapidly in viruses associated with malignant transformations than in viruses
      associated with benign transformations. The E5 proteins display, therefore,
      evolutionary characteristics similar to those of the E6 and E7 oncoproteins. This
      could reflect a differential involvement of the E5 types in the transformation
      processes.

PMID- 15564473
TI  - C-terminal nsP1a protein of human astrovirus colocalizes with the endoplasmic
      reticulum and viral RNA.
AB  - Computational and biological approaches were undertaken to characterize the role
      of the human astrovirus nonstructural protein nsP1a/4, located at the C-terminal
      fragment of nsP1a. Computer analysis reveals sequence similarities to other
      nonstructural viral proteins involved in RNA replication and/or transcription and
      allows the identification of a glutamine- and proline-rich region, the prediction
      of many phosphorylation and O-glycosylation sites, and the occurrence of a KKXX
      like endoplasmic reticulum retention signal. Immunoprecipitation analysis with an
      antibody against a synthetic peptide of the nsP1a/4 sequence detected polyprotein
      precursors of 160, 75, and 38 to 40 kDa as well as five smaller proteins in the
      range of 21 to 27 kDa. Immunofluorescence labeling showed that the nsP1a/4
      protein is accumulated at the perinuclear region, in association with the
      endoplasmic reticulum and the viral RNA. These results suggest the involvement of
      nsP1a/4 protein in the RNA replication process in endoplasmic reticulum-derived
      intracellular membranes.

PMID- 15564474
TI  - Dissection of the Kaposi's sarcoma-associated herpesvirus gene expression program
      by using the viral DNA replication inhibitor cidofovir.
AB  - Treatment of primary effusion lymphoma cells latently infected by Kaposi's
      sarcoma-associated herpesvirus (KSHV; human herpesvirus-8 [HHV-8]) with agents
      such as 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a lytic viral
      replication cycle, with an ordered gene expression program. Initial studies of
      the KSHV expression program following TPA induction using viral microarrays
      yielded useful information concerning the viral expression program, but precise
      kinetic assignments for some genes remained unclear. Classically, late
      herpesvirus genes require viral DNA replication for maximal expression. We used
      cidofovir (CDV), a nucleotide-analogue KSHV DNA polymerase inhibitor, to dissect
      KSHV expression into two components: genes expressed without viral DNA
      replication and those requiring it. The expression of known immediate-early or
      early genes (e.g., open reading frames [ORFs] 50, K8 bZIP, and 57) serving lytic
      regulatory roles was relatively unaffected by the presence of CDV, while known
      late capsid and tegument structural genes (e.g., ORFs 25, 26, 64, and 67) were
      CDV sensitive. Latency-associated transcript ORF 73 was unaffected by the
      presence of TPA or CDV, suggesting that it was constitutively expressed.
      Expression of several viral cellular gene homologs, including K2 (vIL-6), ORF 72
      (vCyclin), ORF 74 (vGPCR), and K9 (vIRF-1), was unaffected by the presence of
      CDV, while that of others, such as K4.1 (vMIP-III), K11.1 (vIRF-2), and K10.5
      (LANA2, vIRF-3), was inhibited. The results distinguish KSHV genes whose full
      expression required viral DNA replication from those that did not require it,
      providing additional insights into KSHV replication and pathogenesis strategies
      and helping to show which viral cell homologs are expressed at particular times
      during the lytic process.

PMID- 15564475
TI  - Nucleolar localization of human hepatitis B virus capsid protein.
AB  - Wild-type human hepatitis B virus (HBV) exhibits selective export of virions
      containing mature genomes. In contrast, changing an isoleucine to a leucine at
      amino acid 97 (I97L) of the HBV core antigen (HBcAg) causes it to release
      immature genomes. To elucidate the structure-function relationship of HBcAg at
      amino acid 97, we systematically replaced the isoleucine residue at this position
      with 18 other amino acids via mutagenesis. Twelve of the 18 mutants exhibited no
      significant phenotype, while five new mutants displayed strong phenotypes. The
      I97D mutant had a near lethal phenotype, the I97P mutant exhibited a
      significantly reduced level of virion secretion, and the I97G mutant lacked the
      full-length relaxed circular form of viral DNA. The tip of the spike of the
      capsid particle is known to contain a predominant B-cell epitope. However, the
      recognition of this exposed epitope by an anti-HBc antibody appeared to be
      affected by the I97E mutation or by histidine tagging at the C terminus of mutant
      HBcAg, which is presumably in the capsid interior. Surprisingly, the nuclear
      HBcAg of mutants I97E and I97W, produced from either a replicon or an expression
      vector, was found to be colocalized with nucleolin and B23 at a frequency of
      nearly 100% by confocal immunofluorescence microscopy. In contrast, this
      colocalization occurred with wild-type HBcAg only to a limited extent. We also
      noted that nucleolin-colocalizing cells were often binucleated or apoptotic,
      suggesting that the presence of HBcAg in the nucleolus may perturb cytokinesis.
      The mechanism of this phenomenon and its potential involvement in liver
      pathogenesis are discussed. To our knowledge, this is the first report of
      nucleolar HBcAg in culture.

PMID- 15564476
TI  - Oligomerization of Hantavirus N protein: C-terminal alpha-helices interact to
      form a shared hydrophobic space.
AB  - The structure of the nucleocapsid protein of bunyaviruses has not been defined.
      Earlier we have shown that Tula hantavirus N protein oligomerization is dependent
      on the C-terminal domains. Of them, the helix-loop-helix motif was found to be an
      essential structure. Computer modeling predicted that oligomerization occurs via
      helix protrusions, and the shared hydrophobic space formed by amino acids
      residues 380-IILLF-384 in the first helix and 413-LI-414 in the second helix is
      responsible for stabilizing the interaction. The model was validated by two
      approaches. First, analysis of the oligomerization capacity of the N protein
      mutants performed with the mammalian two-hybrid system showed that both
      preservation of the helix structure and formation of the shared hydrophobic space
      are crucial for the interaction. Second, oligomerization was shown to be a
      prerequisite for the granular pattern of transiently expressed N protein in
      transfected cells. N protein trimerization was supported by three-dimensional
      reconstruction of the N protein by electron microscopy after negative staining.
      Finally, we discuss how N protein trimerization could occur.

PMID- 15564477
TI  - Intracellular viral processing, not single-stranded DNA accumulation, is crucial
      for recombinant adeno-associated virus transduction.
AB  - Adeno-associated virus (AAV) is a unique gene transfer vector which takes
      approximately 4 to 6 weeks to reach its expression plateau. The mechanism for
      this slow-rise expression profile was proposed to be inefficient second-strand
      DNA synthesis from the input single-stranded (ss) DNA viral genome. In order to
      clarify the status of ss AAV genomes, we generated AAV vectors labeled with
      bromodeoxyuridine (BrdU), a nucleotide analog that can be incorporated into the
      AAV genome and packaged into infectious virions. Since BrdU-DNA can be detected
      only by an anti-BrdU antibody when DNA is in an ss form, not in a double-stranded
      (ds) form, ss AAV genomes with BrdU can be readily tracked in situ. Although ss
      AAV DNA was abundant by Southern blot analysis, free ss AAV genomes were not
      detectable after AAV transduction by this new detection method. Further Southern
      blot analysis of viral DNA and virions revealed that ss AAV DNA was protected
      within virions. Extracted cellular fractions demonstrated that viral particles in
      host cells remained infectious. In addition, a significant amount of AAV genomes
      was degraded after AAV transduction. Therefore, we conclude that the amount of
      free ss DNA is not abundant during AAV transduction. AAV transduction is limited
      by the steps that affect AAV ss DNA release (i.e., uncoating) before second
      strand DNA synthesis can occur. AAV ss DNA released from viral uncoating is
      either converted into ds DNA efficiently or degraded by cellular DNA repair
      mechanisms as damaged DNA. This study elucidates a mechanism that can be
      exploited to develop new strategies to improve AAV vector transduction
      efficiency.

PMID- 15564478
TI  - Antiviral effects of human immunodeficiency virus type 1-specific small
      interfering RNAs against targets conserved in select neurotropic viral strains.
AB  - RNA interference, a natural biological phenomenon mediated by small interfering
      RNAs (siRNAs), has been demonstrated in recent studies to be an effective
      strategy against human immunodeficiency virus type 1 (HIV-1). In the present
      study, we used 21-bp chemically synthesized siRNA duplexes whose sequences were
      derived from the gp41 gene, nef, tat, and rev regions of viral RNA. These
      sequences are conserved in select neurotropic strains of HIV-1 (JR-FL, JR-CSF,
      and YU-2). The designed siRNAs exerted a potent antiviral effect on these HIV-1
      strains. The antiviral effect was mediated at the RNA level (as observed by the
      down-regulation of the HIV-1-specific spliced transcript generating a 1.2-kbp
      reverse transcription [RT]-PCR product) as well as viral assembly on the cell
      membrane. Spliced transcripts (apart from the most abundant transcript generating
      a 1.2-kbp RT-PCR product) arising from an unspliced precursor likely contributed,
      albeit to a lesser extent, to the antiviral effect. The resultant progeny viruses
      had infectivities similar to that of input virus. We therefore conclude that
      these siRNAs interfere with the processing of the unspliced transcripts for the
      gp41 gene, tat, rev, and nef, eventually affecting viral assembly and leading to
      the overall inhibition of viral production. Apart from using the gp41 gene as a
      target, the conservation of each of these targets in the above-mentioned viral
      strains, as well as several primary isolates, would enable these siRNAs to be
      used as potent antiviral tools for investigations with cells derived from the
      central nervous system in order to evaluate their therapeutic potential and
      assess their utility in inhibiting HIV-1 neuropathogenesis and neuroinvasion.

PMID- 15564479
TI  - Accelerated prion disease in the absence of interleukin-10.
AB  - The identity of pro- and anti-inflammatory cytokines in the neuropathogenesis of
      prion diseases remains undefined. Here we have investigated the role of anti
      inflammatory cytokines on the progression of prion disease through the use of
      mice that lack interleukin-4 (IL-4), IL-10, IL-13, or both IL-4 and IL-13.
      Collectively our data show that among these anti-inflammatory cytokines, IL-10
      plays a prominent role in the regulation of prion disease. Mice deficient in IL
      10 are highly susceptible to the development of prion disease and show a markedly
      shortened incubation time. In addition, we have correlated cytokine gene
      expression in prion-inoculated IL-10(-/-) mice to wild-type-inoculated animals.
      Our experiments show that in the absence of IL-10 there is an early expression of
      tumor necrosis factor alpha (TNF-alpha). In wild-type prion-inoculated mice, the
      expression of TNF-alpha mRNA occurs at a later time point that correlates with
      the extended incubation time for terminal disease development in these animals
      compared to those that lack IL-10. Elevated levels of IL-13 mRNA are found at
      early time points in the central nervous system of prion-inoculated IL-10(-/-)
      mice. At terminal disease, the brains of wild-type mice inoculated with RML or
      ME7 are characterized by elevated levels of mRNA for the proinflammatory
      cytokines TNF-alpha and IL-1beta, together with the anti-inflammatory cytokines
      IL-10, IL-13, and transforming growth factor beta. Our data are consistent with a
      role for proinflammatory cytokines in the initiation of pathology during prion
      disease and an attempt by anti-inflammatory cytokines to regulate the ensuing,
      invariably fatal pathology.

PMID- 15564480
TI  - Identification of residues in the dengue virus type 2 NS2B cofactor that are
      critical for NS3 protease activation.
AB  - Proteolytic processing of the dengue virus polyprotein is mediated by host cell
      proteases and the virus-encoded NS2B-NS3 two-component protease. The NS3 protease
      represents an attractive target for the development of antiviral inhibitors. The
      three-dimensional structure of the NS3 protease domain has been determined, but
      the structural determinants necessary for activation of the enzyme by the NS2B
      cofactor have been characterized only to a limited extent. To test a possible
      functional role of the recently proposed Phix(3)Phi motif in NS3 protease
      activation, we targeted six residues within the NS2B cofactor by site-specific
      mutagenesis. Residues Trp62, Ser71, Leu75, Ile77, Thr78, and Ile79 in NS2B were
      replaced with alanine, and in addition, an L75A/I79A double mutant was generated.
      The effects of these mutations on the activity of the NS2B(H)-NS3pro protease
      were analyzed in vitro by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis of autoproteolytic cleavage at the NS2B/NS3 site and by
      assay of the enzyme with the fluorogenic peptide substrate GRR-AMC. Compared to
      the wild type, the L75A, I77A, and I79A mutants demonstrated inefficient
      autoproteolysis, whereas in the W62A and the L75A/I79A mutants self-cleavage
      appeared to be almost completely abolished. With exception of the S71A mutant,
      which had a k(cat)/K(m) value for the GRR-AMC peptide similar to that of the wild
      type, all other mutants exhibited drastically reduced k(cat) values. These
      results indicate a pivotal function of conserved residues Trp62, Leu75, and Ile79
      in the NS2B cofactor in the structural activation of the dengue virus NS3 serine
      protease.

PMID- 15564481
TI  - Protein kinase C-alpha activity is required for respiratory syncytial virus
      fusion to human bronchial epithelial cells.
AB  - Respiratory syncytial virus (RSV) infection activates protein kinase C (PKC), but
      the precise PKC isoform(s) involved and its role(s) remain to be elucidated. On
      the basis of the activation kinetics of different signaling pathways and the
      effect of various PKC inhibitors, it was reasoned that PKC activation is
      important in the early stages of RSV infection, especially RSV fusion and/or
      replication. Herein, the role of PKC-alpha during the early stages of RSV
      infection in normal human bronchial epithelial cells is determined. The results
      show that the blocking of PKC-alpha activation by classical inhibitors,
      pseudosubstrate peptides, or the overexpression of dominant-negative mutants of
      PKC-alpha in these cells leads to significantly decreased RSV infection. RSV
      induces phosphorylation, activation, and cytoplasm-to-membrane translocation of
      PKC-alpha. Also, PKC-alpha colocalizes with virus particles and is required for
      RSV fusion to the cell membrane. Thus, PKC-alpha could provide a new
      pharmacological target for controlling RSV infection.

PMID- 15564482
TI  - Conserved glycine residues in the fusion peptide of the paramyxovirus fusion
      protein regulate activation of the native state.
AB  - Hydrophobic fusion peptides (FPs) are the most highly conserved regions of class
      I viral fusion-mediating glycoproteins (vFGPs). FPs often contain conserved
      glycine residues thought to be critical for forming structures that destabilize
      target membranes. Unexpectedly, a mutation of glycine residues in the FP of the
      fusion (F) protein from the paramyxovirus simian parainfluenza virus 5 (SV5)
      resulted in mutant F proteins with hyperactive fusion phenotypes (C. M. Horvath
      and R. A. Lamb, J. Virol. 66:2443-2455, 1992). Here, we constructed G3A and G7A
      mutations into the F proteins of SV5 (W3A and WR isolates), Newcastle disease
      virus (NDV), and human parainfluenza virus type 3 (HPIV3). All of the mutant F
      proteins, except NDV G7A, caused increased cell-cell fusion despite having slight
      to moderate reductions in cell surface expression compared to those of wild-type
      F proteins. The G3A and G7A mutations cause SV5 WR F, but not NDV F or HPIV3 F,
      to be triggered to cause fusion in the absence of coexpression of its homotypic
      receptor-binding protein hemagglutinin-neuraminidase (HN), suggesting that NDV
      and HPIV3 F have stricter requirements for homotypic HN for fusion activation.
      Dye transfer assays show that the G3A and G7A mutations decrease the energy
      required to activate F at a step in the fusion cascade preceding prehairpin
      intermediate formation and hemifusion. Conserved glycine residues in the FP of
      paramyxovirus F appear to have a primary role in regulating the activation of the
      metastable native form of F. Glycine residues in the FPs of other class I vFGPs
      may also regulate fusion activation.

PMID- 15564483
TI  - Protein transduction domains fused to virus receptors improve cellular virus
      uptake and enhance oncolysis by tumor-specific replicating vectors.
AB  - Expression of cellular receptors determines viral tropism and limits gene
      delivery by viral vectors. Protein transduction domains (PTDs) have been shown to
      deliver proteins, antisense oligonucleotides, liposomes, or plasmid DNA into
      cells. In our study, we investigated the role of several PTD motifs in adenoviral
      infection. When physiologically expressed, a PTD from human immunodeficiency
      virus transactivator of transcription (Tat) did not improve adenoviral infection.
      We therefore fused PTDs to the ectodomain of the coxsackievirus-adenovirus
      receptor (CAR(ex)) to attach PTDs to adenoviral fiber knobs. CAR(ex)-Tat and
      CAR(ex)-VP22 allowed efficient adenoviral infection in nonpermissive cells and
      significantly improved viral uptake rates in permissive cells. Dose-dependent
      competition of CAR(ex)-PTD-mediated infection using CAR(ex) and inhibition
      experiments with heparin showed that binding of CAR(ex)-PTD to both adenoviral
      fiber and cellular glycosaminoglycans is essential for the improvement of
      infection. CAR(ex)-PTD-treated adenoviruses retained their properties after
      density gradient ultracentrifugation, indicating stable binding of CAR(ex)-PTD to
      adenoviral particles. Consequently, the mechanism of CAR(ex)-PTD-mediated
      infection involves coating of the viral fiber knobs by CAR(ex)-PTD, rather than
      placement of CAR(ex) domains on cell surfaces. Expression of CAR(ex)-PTDs led to
      enhanced lysis of permissive and nonpermissive tumor cells by replicating
      adenoviruses, indicating that CAR(ex)-PTDs are valuable tools to improve the
      efficacy of oncolytic therapy. Together, our study shows that CAR(ex)-PTDs
      facilitate gene transfer in nonpermissive cells and improve viral uptake at
      reduced titers and infection times. The data suggest that PTDs fused to virus
      binding receptors may be a valuable tool to overcome natural tropism of vectors
      and could be of great interest for gene therapeutic approaches.

PMID- 15564484
TI  - Glycocalyx restricts adenoviral vector access to apical receptors expressed on
      respiratory epithelium in vitro and in vivo: role for tethered mucins as barriers
      to lumenal infection.
AB  - Inefficient adenoviral vector (AdV)-mediated gene transfer to the ciliated
      respiratory epithelium has hindered gene transfer strategies for the treatment of
      cystic fibrosis lung disease. In part, the inefficiency is due to an absence of
      the coxsackie B and adenovirus type 2 and 5 receptor (CAR) from the apical
      membranes of polarized epithelia. In this study, using an in vitro model of human
      ciliated airway epithelium, we show that providing a glycosylphosphatidylinositol
      (GPI)-linked AdV receptor (GPI-CAR) at the apical surface did not significantly
      improve AdV gene transfer efficiency because the lumenal surface glycocalyx
      limited the access of AdV to apical GPI-CAR. The highly glycosylated tethered
      mucins were considered to be significant glycocalyx components that restricted
      AdV access because proteolytic digestion and inhibitors of O-linked glycosylation
      enhanced AdV gene transfer. To determine whether these in vitro observations are
      relevant to the in vivo situation, we generated transgenic mice expressing GPI
      CAR at the surface of the airway epithelium, crossbred these mice with mice that
      were genetically devoid of tethered mucin type 1 (Muc1), and tested the
      efficiency of gene transfer to murine airways expressing apical GPI-human CAR
      (GPI-hCAR) in the presence and absence of Muc1. We determined that AdV gene
      transfer to the murine airway epithelium was inefficient even in GPI-hCAR
      transgenic mice but that the gene transfer efficiency improved in the absence of
      Muc1. However, the inability to achieve a high gene transfer efficiency, even in
      mice with a deletion of Muc1, suggested that other glycocalyx components,
      possibly other tethered mucin types, also provide a significant barrier to AdV
      interacting with the airway lumenal surface.

PMID- 15564485
TI  - Human papillomavirus type 16 E6 promotes retinoblastoma protein phosphorylation
      and cell cycle progression.
AB  - We show that E6 proteins from benign human papillomavirus type 1 (HPV1) and
      oncogenic HPV16 have the ability to alter the regulation of the G(1)/S transition
      of the cell cycle in primary human fibroblasts. Overexpression of both viral
      proteins induces cellular proliferation, retinoblastoma (pRb) phosphorylation,
      and accumulation of products of genes that are negatively regulated by pRb, such
      as p16(INK4a), CDC2, E2F-1, and cyclin A. Hyperphosphorylated forms of pRb are
      present in E6-expressing cells even in the presence of ectopic levels of
      p16(INK4a). The E6 proteins strongly increased the cyclin A/cyclin-dependent
      kinase 2 (CDK2) activity, which is involved in pRb phosphorylation. In addition,
      mRNA and protein levels of the CDK2 inhibitor p21(WAF1/CIP1) were strongly down
      regulated in cells expressing E6 proteins. The down-regulation of the
      p21(WAF1/CIP1) gene appears to be independent of p53 inactivation, since HPV1 E6
      and an HPV16 E6 mutant unable to target p53 were fully competent in decreasing
      p21(WAF1/CIP1) levels. E6 from HPV1 and HPV16 also enabled cells to overcome the
      G(1) arrest imposed by oncogenic ras. Immunofluorescence staining of cells
      coexpressing ras and E6 from either HPV16 or HPV1 revealed that antiproliferative
      (p16(INK4a)) and proliferative (Ki67) markers were coexpressed in the same cells.
      Together, these data underline a novel activity of E6 that is not mediated by
      inactivation of p53.

PMID- 15564486
TI  - Intrahepatic gene expression during chronic hepatitis C virus infection in
      chimpanzees.
AB  - Hepatitis C virus (HCV) infections represent a global health problem and are a
      major contributor to end-stage liver disease including cirrhosis and
      hepatocellular carcinoma. An improved understanding of the parameters involved in
      disease progression is needed to develop better therapies and diagnostic markers
      of disease manifestation. To better understand the dynamics of host gene
      expression resulting from persistent virus infection, DNA microarray analyses
      were conducted on livers from 10 chimpanzees persistently infected with HCV. A
      total of 162 genes were differentially regulated in chronically infected animals
      compared to uninfected controls. Many genes exhibited a remarkable consistency in
      changes in expression in the 10 chronically infected animals. A second method of
      analysis identified 971 genes altered in expression during chronic infection at a
      99% confidence level. As with acute-resolving HCV infections, many interferon
      (IFN)-stimulated genes (ISGs) were transcriptionally elevated, suggesting an
      ongoing response to IFN and/or double-stranded RNA which is amplified in
      downstream ISG expression. Thus, persistent infection with HCV results in a
      complex and partially predictable pattern of gene expression, although the
      underlying mechanisms regulating the different pathways are not well defined. A
      single genotype 3-infected animal was available for analysis, and this animal
      exhibited reduced levels of ISG expression compared to levels of expression with
      genotype 1 infections and increased expression of a number of genes potentially
      involved in steatosis. Gene expression data in concert with other observations
      from HCV infections permit speculation on the regulation of specific aspects of
      HCV infection.

PMID- 15564487
TI  - Replicon system for Lassa virus.
AB  - Lassa virus is endemic to West Africa and causes hemorrhagic fever in humans. To
      facilitate the functional analysis of this virus, a replicon system was developed
      based on Lassa virus strain AV. Genomic and antigenomic minigenomes (MG) were
      constructed consisting of the intergenic region of S RNA and a reporter gene
      (Renilla luciferase) in antisense orientation, flanked by the 5' and 3'
      untranslated regions of S RNA. MGs were expressed under the control of the T7
      promoter. Nucleoprotein (NP), L protein, and Z protein were expressed from
      plasmids containing the T7 promoter and internal ribosomal entry site.
      Transfection of cells stably expressing T7 RNA polymerase (BSR T7/5) with MG in
      the form of DNA or RNA and plasmids for the expression of NP and L protein
      resulted in high levels of Renilla luciferase expression. The replicon system was
      optimized with respect to the ratio of the transfected constructs and by
      modifying the 5' end of the MG. Maximum activity was observed 24 to 36 h after
      transfection with a signal-to-noise ratio of 2 to 3 log units. Northern blot
      analysis provided evidence for replication and transcription of the MG. Z protein
      downregulated replicon activity close to background levels. Treatment with
      ribavirin and alpha interferon inhibited replicon activity, suggesting that both
      act on the level of RNA replication, transcription, or ribonucleoprotein
      assembly. In conclusion, this study describes the first replicon system for a
      highly pathogenic arenavirus. It is a tool for investigating the mechanisms of
      replication and transcription of Lassa virus and may facilitate the testing of
      antivirals outside a biosafety level 4 laboratory.

PMID- 15564488
TI  - Recombinant infectious bronchitis coronavirus Beaudette with the spike protein
      gene of the pathogenic M41 strain remains attenuated but induces protective
      immunity.
AB  - We have replaced the ectodomain of the spike (S) protein of the Beaudette strain
      (Beau-R; apathogenic for Gallus domesticus chickens) of avian infectious
      bronchitis coronavirus (IBV) with that from the pathogenic M41 strain to produce
      recombinant IBV BeauR-M41(S). We have previously shown that this changed the
      tropism of the virus in vitro (R. Casais, B. Dove, D. Cavanagh, and P. Britton,
      J. Virol. 77:9084-9089, 2003). Herein we have assessed the pathogenicity and
      immunogenicity of BeauR-M41(S). There were no consistent differences in
      pathogenicity between the recombinant BeauR-M41(S) and its apathogenic parent
      Beau-R (based on snicking, nasal discharge, wheezing, watery eyes, rales, and
      ciliostasis in trachea), and both replicated poorly in trachea and nose compared
      to M41; the S protein from the pathogenic M41 had not altered the apathogenic
      nature of Beau-R. Both Beau-R and BeauR-M41(S) induced protection against
      challenge with M41 as assessed by absence of recovery of challenge virus and
      nasal exudate. With regard to snicking and ciliostasis, BeauR-M41(S) induced
      greater protection (seven out of nine chicks [77%]; assessed by ciliostasis) than
      Beau-R (one out of nine; 11%) but less than M41 (100%). The greater protection
      induced by BeauR-M41(S) against M41 may be related to the ectodomain of the spike
      protein of Beau-R differing from that of M41 by 4.1%; a small number of epitopes
      on the S protein may play a disproportionate role in the induction of immunity.
      The results are promising for the prospects of S-gene exchange for IBV vaccine
      development.

PMID- 15564489
TI  - Hepatitis B virus nucleocapsids formed by carboxy-terminally mutated core
      proteins contain spliced viral genomes but lack full-size DNA.
AB  - The carboxy-terminal sequence of the hepatitis B virus (HBV) core protein
      constitutes a nucleic acid binding domain that is rich in arginine residues and
      contains three serine phosphorylation sites. While dispensable for capsid
      assembly, this domain is involved in viral replication, as demonstrated by the
      effects of mutations on RNA packaging and/or reverse transcription; however, the
      underlying mechanisms are poorly understood. Here we tested a series of core
      protein mutants in which the three serine phosphorylation sites were replaced by
      glutamic acid, in parallel with a previously described deletion variant lacking
      the 19 C-terminal amino acid residues, for their ability to support viral
      replication in transfected hepatoma cells. Replacement of all serines and the
      deletion gave rise to nucleocapsids containing a smaller than wild-type DNA
      genome. Rather than a single-stranded DNA intermediate, as previously thought,
      this was a 2.0-kbp double-stranded DNA molecule derived from spliced pregenomic
      RNA (pgRNA). Interestingly, full-length pgRNA was associated with nucleocapsids
      but was found to be sensitive to nuclease digestion, while encapsidated spliced
      RNA and 3' truncated RNA species were nuclease resistant. These findings suggest
      that HBV pgRNA encapsidation is directional and that a packaging limit is
      determined by the C-terminal portion of the core protein.

PMID- 15564490
TI  - Efficacy of DNA and fowlpox virus priming/boosting vaccines for simian/human
      immunodeficiency virus.
AB  - Further advances are required in understanding protection from AIDS by T-cell
      immunity. We analyzed a set of multigenic simian/human immunodeficiency virus
      (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and
      protective efficacy in outbred pigtail macaques. The number of vaccinations
      required, the effect of DNA vaccination alone, and the effect of cytokine (gamma
      interferon) coexpression by the fowlpox virus boost was also studied. A
      coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell
      immune responses was induced by sequential DNA and fowlpox virus vaccination. The
      immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon,
      a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant
      control of a virulent SHIV challenge was observed despite a loss of SHIV-specific
      proliferating T cells. The outcome of challenge with virulent SHIV(mn229)
      correlated with vaccine immunogenicity except that DNA vaccination alone primed
      for protection almost as effectively as the DNA/fowlpox virus regimen despite
      negligible immunogenicity by standard assays. These studies suggest that priming
      of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.

PMID- 15564491
TI  - Genome assembly and particle maturation of the birnavirus infectious pancreatic
      necrosis virus.
AB  - In this study, we have analyzed the morphogenesis of the birnavirus infectious
      pancreatic necrosis virus throughout the infective cycle in CHSE-214 cells by
      using a native agarose electrophoresis system. Two types of viral particles
      (designated A and B) were identified, isolated, and characterized both
      molecularly and biologically. Together, our results are consistent with a model
      of morphogenesis in which the genomic double-stranded RNA is immediately
      assembled, after synthesis, into a large (66-nm diameter) and uninfectious
      particle A, where the capsid is composed of both mature and immature viral
      polypeptides. Upon maturation, particles A yield particles B through the
      proteolytic cleavage of most of the remaining viral precursors within the capsid,
      the compaction of the particle (60-nm diameter), and the acquisition of
      infectivity. These studies will provide the foundation for further analyses of
      birnavirus particle assembly and RNA replication.

PMID- 15564492
TI  - Long-term excretion of vaccine-derived poliovirus by a healthy child.
AB  - A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a
      1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6
      months after he was immunized with oral live polio vaccine. Seventeen type 1
      poliovirus isolates were recovered from stools taken from this child during the
      following 4 months. Contrary to expectation, the child was not deficient in
      humoral immunity and showed high levels of serum neutralization against
      poliovirus. Selected virus isolates were characterized in terms of their
      antigenic properties, virulence in transgenic mice, sensitivity for growth at
      high temperatures, and differences in nucleotide sequence from the Sabin type 1
      strain. The VDPV isolates showed mutations at key nucleotide positions that
      correlated with the observed reversion to biological properties typical of wild
      polioviruses. A number of capsid mutations mapped at known antigenic sites
      leading to changes in the viral antigenic structure. Estimates of sequence
      evolution based on the accumulation of nucleotide changes in the VP1 coding
      region detected a "defective" molecular clock running at an apparent faster speed
      of 2.05% nucleotide changes per year versus 1% shown in previous studies.
      Remarkably, when compared to several type 1 VDPV strains of different origins,
      isolates from this child showed a much higher proportion of nonsynonymous versus
      synonymous nucleotide changes in the capsid coding region. This anomaly could
      explain the high VP1 sequence drift found and the ability of these virus strains
      to replicate in the gut for a longer period than expected.

PMID- 15564493
TI  - Overlapping CRE and E box motifs in the enhancer sequences of the bovine leukemia
      virus 5' long terminal repeat are critical for basal and acetylation-dependent
      transcriptional activity of the viral promoter: implications for viral latency.
AB  - Bovine leukemia virus (BLV) infection is characterized by viral latency in a
      large proportion of cells containing an integrated provirus. In this study, we
      postulated that mechanisms directing the recruitment of deacetylases to the BLV
      5' long terminal repeat (LTR) could explain the transcriptional repression of
      viral expression in vivo. Accordingly, we showed that BLV promoter activity was
      induced by several deacetylase inhibitors (such as trichostatin A [TSA]) in the
      context of episomal LTR constructs and in the context of an integrated BLV
      provirus. Moreover, treatment of BLV-infected cells with TSA increased H4
      acetylation at the viral promoter, showing a close correlation between the level
      of histone acetylation and transcriptional activation of the BLV LTR. Among the
      known cis-regulatory DNA elements located in the 5' LTR, three E box motifs
      overlapping cyclic AMP responsive elements (CREs) in U3 were shown to be involved
      in transcriptional repression of BLV basal gene expression. Importantly, the
      combined mutations of these three E box motifs markedly reduced the inducibility
      of the BLV promoter by TSA. E boxes are susceptible to recognition by
      transcriptional repressors such as Max-Mad-mSin3 complexes that repress
      transcription by recruiting deacetylases. However, our in vitro binding studies
      failed to reveal the presence of Mad-Max proteins in the BLV LTR E box-specific
      complexes. Remarkably, TSA increased the occupancy of the CREs by CREB/ATF.
      Therefore, we postulated that the E box-specific complexes exerted their negative
      cooperative effect on BLV transcription by steric hindrance with the activators
      CREB/ATF and/or their transcriptional coactivators possessing acetyltransferase
      activities. Our results thus suggest that the overlapping CRE and E box elements
      in the BLV LTR were selected during evolution as a novel strategy for BLV to
      allow better silencing of viral transcription and to escape from the host immune
      response.

PMID- 15564494
TI  - Prototype foamy virus envelope glycoprotein leader peptide processing is mediated
      by a furin-like cellular protease, but cleavage is not essential for viral
      infectivity.
AB  - Analogous to cellular glycoproteins, viral envelope proteins contain N-terminal
      signal sequences responsible for targeting them to the secretory pathway. The
      prototype foamy virus (PFV) envelope (Env) shows a highly unusual biosynthesis.
      Its precursor protein has a type III membrane topology with both the N and C
      terminus located in the cytoplasm. Coexpression of FV glycoprotein and
      interaction of its leader peptide (LP) with the viral capsid is essential for
      viral particle budding and egress. Processing of PFV Env into the particle
      associated LP, surface (SU), and transmembrane (TM) subunits occur
      posttranslationally during transport to the cell surface by yet-unidentified
      cellular proteases. Here we provide strong evidence that furin itself or a furin
      like protease and not the signal peptidase complex is responsible for both
      processing events. N-terminal protein sequencing of the SU and TM subunits of
      purified PFV Env-immunoglobulin G immunoadhesin identified furin consensus
      sequences upstream of both cleavage sites. Mutagenesis analysis of two
      overlapping furin consensus sequences at the PFV LP/SU cleavage site in the wild
      type protein confirmed the sequencing data and demonstrated utilization of only
      the first site. Fully processed SU was almost completely absent in viral
      particles of mutants having conserved arginine residues replaced by alanines in
      the first furin consensus sequence, but normal processing was observed upon
      mutation of the second motif. Although these mutants displayed a significant loss
      in infectivity as a result of reduced particle release, no correlation to
      processing inhibition was observed, since another mutant having normal LP/SU
      processing had a similar defect.

PMID- 15564495
TI  - Determinants of high titer in recombinant porcine endogenous retroviruses.
AB  - Porcine endogenous retroviruses (PERVs) pose a potential stumbling block for
      therapeutic xenotransplantation, with the greatest threat coming from viruses
      generated by recombination between members of the PERV subgroup A (PERV-A) and
      PERV-C families (PERV-A/C recombinants). PERV-A and PERV-B have been shown to
      infect human cells in culture, albeit with low titers. PERV-C has a more
      restricted host range and cannot infect human cells. A recombinant PERV-A/C virus
      (PERV-A14/220) contains the PERV-A sequence between the end of pol and the middle
      of the SU region in env. The remaining sequence is derived from PERV-C. PERV
      A14/220 is approximately 500-fold more infectious than PERV-A. To determine the
      molecular basis for the increased infectivity of PERV-A14/220, we have made a
      series of vector constructs. The primary determinant for the enhanced replicative
      potential of the recombinant virus appeared to be the env gene. Using a series of
      chimeric env genes, we could identify two determinants of high infectivity; one
      was an isoleucine to valine substitution at position 140 between variable regions
      A and B, and the other lies within the proline rich region. Taken together, these
      results show that the novel juxtaposition of env gene sequences enhanced the
      infectivity of PERV-A14/220 for human cells, perhaps by stabilization of the
      envelope glycoprotein or increased receptor binding.

PMID- 15564496
TI  - Evidence and consequence of porcine endogenous retrovirus recombination.
AB  - The genetic nature and biological effects of recombination between porcine
      endogenous retroviruses (PERV) were studied. An infectious molecular clone was
      generated from a high-titer, human-tropic PERV isolate, PERV-A 14/220 (B. A.
      Oldmixon, et al. J. Virol. 76:3045-3048, 2002; T. A. Ericsson et al. Proc. Natl.
      Acad. Sci. USA 100:6759-6764, 2003). To analyze this sequence and 15 available
      full-length PERV nucleotide sequences, we developed a sequence comparison
      program, LOHA(TM) to calculate local sequence homology between two sequences.
      This analysis determined that PERV-A 14/220 arose by homologous recombination of
      a PERV-C genome replacing an 850-bp region around the pol-env junction with that
      of a PERV-A sequence. This 850-bp PERV-A sequence encompasses the env receptor
      binding domain, thereby conferring a wide host range including human cells. In
      addition, we determined that multiple regions derived from PERV-C are responsible
      for the increased infectious titer of PERV-A 14/220. Thus, a single recombination
      event may be a fast and effective way to generate high-titer, potentially harmful
      PERV. Further, local homology and phylogenetic analyses between 16 full-length
      sequences revealed evidence for other recombination events in the past that give
      rise to other PERV genomes that possess the PERV-A, but not the PERV-B, env gene.
      These results indicate that PERV-A env is more prone to recombination with
      heterogeneous backbone genomes than PERV-B env. Such recombination events that
      generate more active PERV-A appear to occur in pigs rather frequently, which
      increases the potential risk of zoonotic PERV transmission. In this context, pigs
      lacking non-human-tropic PERV-C would be more suitable as donor animals for
      clinical xenotransplantation.

PMID- 15564497
TI  - Experimental infection of NOD/SCID mice reconstituted with human CD34+ cells with
      Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV)-induced lymphoproliferative disease is an important
      complication in the context of immune deficiency. Impaired T-cell immunity allows
      the outgrowth of transformed cells with the subsequent production of
      predominantly B-cell lymphomas. Currently there is no in vivo model that can
      adequately recapitulate EBV infection and its association with B-cell lymphomas.
      NOD/SCID mice engrafted with human CD34(+) cells and reconstituted mainly with
      human B lymphocytes may serve as a useful xenograft model to study EBV infection
      and pathogenesis. We therefore infected reconstituted mice with EBV. High levels
      of viral DNA were detected in the peripheral blood of all infected mice. All
      infected mice lost weight and showed decreased activity levels. Infected mice
      presented large visible tumors in multiple organs, most prominently in the
      spleen. These tumors stained positive for human CD79a, CD20, CD30, and EBV
      encoded RNAs and were light chain restricted. Their characterization is
      consistent with that of large cell immunoblastic lymphoma. In addition, tumor
      cells expressed EBNA1, LMP1, and LMP2a mRNAs, which is consistent with a type II
      latency program. EBV(+) lymphoblastoid cell lines expressing human CD45, CD19,
      CD21, CD23, CD5, and CD30 were readily established from the bone marrow and
      spleens of infected animals. Finally, we also demonstrate that infection with an
      enhanced green fluorescent protein (EGFP)-tagged virus can be monitored by the
      detection of infected EGFP(+) cells and EGFP(+) tumors. These data demonstrate
      that NOD/SCID mice that are reconstituted with human CD34(+) cells are
      susceptible to infection by EBV and accurately recapitulate important aspects of
      EBV pathogenesis.

PMID- 15564498
TI  - Fitness costs limit viral escape from cytotoxic T lymphocytes at a structurally
      constrained epitope.
AB  - The intense selection pressure exerted by virus-specific cytotoxic T lymphocytes
      (CTL) on replicating human immunodeficiency virus and simian immunodeficiency
      virus results in the accumulation of CTL epitope mutations. It has been assumed
      that fitness costs can limit the evolution of CTL epitope mutations. However,
      only a limited number of studies have carefully examined this possibility. To
      explore the fitness costs associated with viral escape from p11C, C-M-specific
      CTL, we constructed a panel of viruses encoding point mutations at each position
      of the entire p11C, C-M epitope. Amino acid substitutions at positions 3, 4, 5,
      6, 7, and 9 of the epitope significantly impaired virus replication by altering
      virus production and Gag protein expression as well as by destabilizing mature
      cores. Amino acid substitutions at position 2 of the epitope were tolerated but
      required reversion or additional compensatory mutations to generate replication
      competent viruses. Finally, while amino acid substitutions at positions 1 and 8
      of the p11C, C-M epitope were functionally tolerated, these substitutions were
      recognized by p11C, C-M-specific CTL and therefore provided no selection
      advantage for the virus. Together, these data suggest that limited sequence
      variation is tolerated by the region of the capsid encoding the p11C, C-M epitope
      and therefore that only a very limited number of mutations can allow successful
      viral escape from the p11C, C-M-specific CTL response.

PMID- 15564499
TI  - Inhibition of parainfluenza virus type 3 and Newcastle disease virus
      hemagglutinin-neuraminidase receptor binding: effect of receptor avidity and
      steric hindrance at the inhibitor binding sites.
AB  - Zanamivir (4-guanidino-Neu5Ac2en [4-GU-DANA]) inhibits not only the neuraminidase
      activity but also the receptor interaction of the human parainfluenza virus type
      3 (HPIV3) hemagglutinin-neuraminidase (HN), blocking receptor binding and
      subsequent fusion promotion. All activities of the HPIV3 variant ZM1 HN
      (T193I/I567V) are less sensitive to 4-GU-DANA's effects. The T193I mutation in HN
      confers both increased receptor binding and increased neuraminidase activity, as
      well as reduced sensitivities of both activities to 4-GU-DANA inhibition,
      consistent with a single site on the HN molecule carrying out both catalysis and
      binding. We now provide evidence that the HPIV3 variant's resistance to receptor
      binding inhibition by 4-GU-DANA is related to a reduced affinity of the HN
      receptor-binding site for this compound as well as to an increase in the avidity
      of HN for the receptor. Newcastle disease virus (NDV) HN and HPIV3 HN respond
      differently to inhibition in ways that suggest a fundamental distinction between
      them. NDV HN-receptor binding is less sensitive than HPIV3 HN-receptor binding to
      4-GU-DANA, while its neuraminidase activity is highly sensitive. Both HPIV3 and
      NDV HNs are sensitive to receptor-binding inhibition by the smaller molecule
      DANA. However, for NDV HN, some receptor binding cannot be inhibited. These data
      are consistent with the presence in NDV HN of a second receptor-binding site that
      is devoid of enzyme activity and has a negligible, if any, affinity for 4-GU
      DANA. Avidity for the receptor contributes to resistance by allowing the receptor
      to compete effectively with inhibitors for interaction with HN, while the further
      determinant of resistance is the reduced binding of the inhibitor molecule to the
      binding pocket on HN. Based upon our data and recent three-dimensional structural
      information on the HPIV3 and NDV HNs, we propose mechanisms for the observed
      sensitivity and resistance of HN to receptor-binding inhibition and discuss the
      implications of these mechanisms for the distribution of HN functions.

PMID- 15564500
TI  - Cooperation between different forms of the human papillomavirus type 1 E4 protein
      to block cell cycle progression and cellular DNA synthesis.
AB  - Posttranslational modification-oligomerization, phosphorylation, and proteolytic
      cleavage-of the human papillomavirus (HPV) E4 protein occurs as the infected
      keratinocytes migrate up through the suprabasal wart layers. It has been
      postulated that these events modify E4 function during the virus life cycle. In
      HPV type 1 (HPV1)-induced warts, N-terminal sequences are progressively cleaved
      from the full-length E4 protein (E1(wedge)E4) of 17 kDa to produce a series of
      polypeptides of 16, 11 and 10 kDa. Here, we have shown that in human
      keratinocytes, a truncated protein (E4-16K), equivalent to the 16-kDa species,
      mediated a G(2) arrest in the cell cycle that was dependent on a threonine amino
      acid in a proline-rich domain of the protein. Reconstitution of cyclin B1
      expression in E4-16K cells reversed the G(2) arrest. Expression of E4-16K also
      induced chromosomal rereplication, and this was associated with aberrant nuclear
      morphology. Perturbation of the mitotic cell cycle was a biological activity
      specific to the truncated protein. However, coexpression of the full-length
      E1(wedge)E4 protein and the truncated E4-16K protein inhibited normal cellular
      proliferation and cellular DNA rereplication but did not prevent cells from
      arresting in G(2). Our findings provide the first evidence to support the
      hypothesis that proteolytic cleavage of the E1(wedge)E4 protein modifies its
      function. Also, different forms of the HPV1 E4 protein cooperate to negatively
      influence keratinocyte proliferation. We predict that these distinct biological
      activities of E4 act to support efficient amplification of the viral genome in
      suprabasal keratinocytes.

PMID- 15564501
TI  - Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV
      1- and HIV-2-infected individuals in Senegal.
AB  - Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent
      than HIV-1 infection, which may permit the host to mount more effective,
      sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T
      cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected
      Senegalese patients to determine if differences relate to more efficient HIV-2
      control. Homologous HIV-specific T cells were detected in similar frequencies
      (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming
      cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection,
      respectively. Gag-specific responses predominated in both groups (>/=64%), and
      significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than
      HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more
      frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the
      mean magnitude was similar. Total frequencies of HIV-specific responses in both
      groups did not correlate with plasma viral load and CD4(+) T-cell count in
      multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific
      responses was significantly associated with lower plasma viremia in HIV-1
      infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing
      HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1
      infected patients. These findings indicate that improved control of HIV-2
      infection may relate to the contribution of T-helper cell responses. By contrast,
      the superior control of HIV-1 replication associated with HIV-2 Gag responses
      suggests that these may represent cross-reactive, higher-avidity T cells
      targeting epitopes within Gag regions of functional importance in HIV
      replication.

PMID- 15564502
TI  - Role of Nedd4 and ubiquitination of Rous sarcoma virus Gag in budding of virus
      like particles from cells.
AB  - Rous sarcoma virus (RSV) budding requires an interaction of the L domain within
      the p2b region of Gag with cellular Nedd4-family E3 ubiquitin protein ligases.
      Members of our laboratories previously demonstrated that overexpression of a
      fragment of the chicken Nedd4-like protein (LDI-1 WW) inhibits Gag release in a
      dominant-negative manner (A. Kikonyogo, F. Bouamr, M. L. Vana, Y. Xiang, A.
      Aiyar, C. Carter, and J. Leis, Proc. Natl. Acad. Sci. USA 98:11199-11204, 2001).
      We have now identified the complete 3' end of LDI-1 and determined that it has a
      C-terminal ubiquitin ligase HECT domain, similar to other Nedd4 family members.
      While overexpression of the full-length LDI-1 clone (LDI-1 FL) had little effect
      on Gag budding, an LDI-1 FL mutant with a substitution in the HECT domain
      catalytic site blocked Gag release, similar to LDI-1 WW. The coexpression of Gag
      and hemagglutinin-tagged ubiquitin (HA-Ub) resulted in the detection of mono- and
      polyubiquitinated forms of Gag in cells and mostly monoubiquitinated Gag in virus
      like particles (VLPs). When the Nedd4-binding site (L domain) was deleted,
      ubiquitinated Gag was not detected. Interestingly, the release of Gag with
      ubiquitin covalently linked to the C terminus (Gag-Ub) was still blocked by LDI-1
      WW. To understand the mechanism of this inhibition, we examined cells expressing
      Gag and LDI-1 WW by electron microscopy. In the presence of LDI-1 WW, VLPs were
      found in electron-dense inclusion bodies in the cytoplasm of transfected cells.
      In contrast, when cells that coexpressed Gag-Ub and LDI-1 WW were examined,
      inclusion bodies were detected but did not contain VLPs. These results indicate
      that the ubiquitination of Gag is dependent upon Nedd4 binding to the L domain
      and suggest that Nedd4 has additional functions during RSV release besides the
      ubiquitination of Gag.

PMID- 15564503
TI  - Cyclin/CDK regulates the nucleocytoplasmic localization of the human
      papillomavirus E1 DNA helicase.
AB  - Cyclin-dependent kinases (CDKs) play key roles in eukaryotic DNA replication and
      cell cycle progression. Phosphorylation of components of the preinitiation
      complex activates replication and prevents reinitiation. One mechanism is
      mediated by nuclear export of critical proteins. Human papillomavirus (HPV) DNA
      replication requires cellular machinery in addition to the viral replicative DNA
      helicase E1 and origin recognition protein E2. E1 phosphorylation by cyclin/CDK
      is critical for efficient viral DNA replication. We now show that E1 is
      phosphorylated by CDKs in vivo and that phosphorylation regulates its
      nucleocytoplasmic localization. We identified a conserved regulatory region for
      localization which contains a dominant leucine-rich nuclear export sequence
      (NES), the previously defined cyclin binding motif, three serine residues that
      are CDK substrates, and a putative bipartite nuclear localization sequence. We
      show that E1 is exported from the nucleus by a CRM1-dependent mechanism unless
      the NES is inactivated by CDK phosphorylation. Replication activities of E1
      phosphorylation site mutations are reduced and correlate inversely with their
      increased cytoplasmic localization. Nuclear localization and replication
      activities of most of these mutations are enhanced or restored by mutations in
      the NES. Collectively, our data demonstrate that CDK phosphorylation controls E1
      nuclear localization to support viral DNA amplification. Thus, HPV adopts and
      adapts the cellular regulatory mechanism to complete its reproductive program.

PMID- 15564504
TI  - A DNAbeta associated with Tomato yellow leaf curl China virus is required for
      symptom induction.
AB  - We report here that all 25 isolates of Tomato yellow leaf curl China virus
      (TYLCCNV) collected from tobacco, tomato, or Siegesbeckia orientalis plants in
      different regions of Yunnan Province, China, were associated with DNAbeta
      molecules. To investigate the biological role of DNAbeta, full-length infectious
      clones of viral DNA and DNAbeta of TYLCCNV isolate Y10 (TYLCCNV-Y10) were
      agroinoculated into Nicotiana benthamiana, Nicotiana glutinosa, Nicotiana.
      tabacum Samsun (NN or nn), tomato, and petunia plants. We found that TYLCCNV-Y10
      alone could systemically infect these plants, but no symptoms were induced.
      TYLCCNV-Y10 DNAbeta was required, in addition to TYLCCNV-Y10, for induction of
      leaf curl disease in these hosts. Similar to TYLCCNV-Y10, DNAbeta of TYLCCNV
      isolate Y64 was also found to be required for induction of typical leaf curl
      diseases in the hosts tested. When the betaC1 gene of TYLCCNV-Y10 DNAbeta was
      mutated, the mutants failed to induce leaf curl symptoms in N. benthamiana when
      coinoculated with TYLCCNV-Y10. However, Southern blot hybridization analyses
      showed that the mutated DNAbeta molecules were replicated. When N. benthamiana
      and N. tabacum plants were transformed with a construct containing the betaC1
      gene under the control of the Cauliflower mosaic virus 35S promoter, many
      transgenic plants developed leaf curl symptoms similar to those caused by a
      virus, the severity of which paralleled the level of betaC1 transcripts, while
      transgenic plants transformed with the betaC1 gene containing a stop codon after
      the start codon remained symptomless. Thus, expression of a betaC1 gene is
      adequate for induction of symptoms of viral infection in the absence of virus.

PMID- 15564505
TI  - Localization and characterization of flavivirus envelope glycoprotein cross
      reactive epitopes.
AB  - The flavivirus E glycoprotein, the primary antigen that induces protective
      immunity, is essential for membrane fusion and mediates binding to cellular
      receptors. Human flavivirus infections stimulate virus species-specific as well
      as flavivirus cross-reactive immune responses. Flavivirus cross-reactive
      antibodies in human sera create a serious problem for serodiagnosis, especially
      for secondary flavivirus infections, due to the difficulty of differentiating
      primary from secondary cross-reactive serum antibodies. The presence of
      subneutralizing levels of flavivirus cross-reactive serum antibodies may result
      in a dramatic increase in the severity of secondary flavivirus infections via
      antibody-dependent enhancement. An understanding of flavivirus E-glycoprotein
      cross-reactive epitopes is therefore critical for improving public health
      responses to these serious diseases. We identified six E-glycoprotein residues
      that are incorporated into three distinct flavivirus cross-reactive epitopes. Two
      of these epitopes which are recognized by distinct monoclonal antibodies contain
      overlapping continuous residues located within the highly conserved fusion
      peptide. The third epitope consists of discontinuous residues that are
      structurally related to the strictly conserved tryptophan at dengue virus
      serotype 2 E-glycoprotein position 231.

PMID- 15564506
TI  - Attenuating mutations in coxsackievirus B3 map to a conformational epitope that
      comprises the puff region of VP2 and the knob of VP3.
AB  - Ten antibody escape mutants of coxsackievirus B3 (CVB3) were used to identify
      nucleotide substitutions that determine viral virulence for the heart and
      pancreas. The P1 region, encoding the structural genes of each mutant, was
      sequenced to identify mutations associated with the lack of neutralization. Eight
      mutants were found to have a lysine-to arginine mutation in the puff region of
      VP2, while two had a glutamate-to-glycine substitution in the knob of VP3. Two
      mutants, EM1 and EM10, representing each of these mutations, were further
      analyzed, initially by determining their entire sequence. In addition to the
      mutations in P1, EM1 was found to have two mutations in the 3D polymerase, while
      EM10 had a mutation in stem-loop II of the 5' nontranslated region (5'NTR). The
      pathogenesis of the mutants relative to that of CVB3 strain RK [CVB3(RK)] then
      was examined in A/J mice. Both mutants were found to be less cardiotropic than
      the parental strain, with a 40-fold (EM1) or a 100- to 1,000-fold (EM10)
      reduction in viral titers in the heart relative to the titers of CVB3(RK). The
      mutations in VP2, VP3, and the 5'NTR were introduced independently into the RK
      infectious clone, and the phenotypes of the progeny viruses were determined. The
      results substantiated that the VP2 and VP3 mutations reduced cardiovirulence,
      while the 5'NTR mutation in EM10 was associated with a more virulent phenotype
      when expressed on its own. Stereographic imaging of the two mutations in the
      capsomer showed that they lie in close proximity on either side of a narrow cleft
      between the puff and the knob, forming a conformational epitope that is part of
      the putative binding site for coreceptor DAF.

PMID- 15564507
TI  - Human metapneumovirus persists in BALB/c mice despite the presence of
      neutralizing antibodies.
AB  - Human metapneumovirus (HMPV) has emerged as an important human respiratory
      pathogen causing upper and lower respiratory tract infections in young children
      and older adults. Recent epidemiological evidence indicates that HMPV may
      cocirculate with respiratory syncytial virus, and HMPV infection has been
      associated with other respiratory diseases. In this study, we show that BALB/c
      mice are susceptible to HMPV infection, the virus replicates in the lungs with
      biphasic growth kinetics in which peak titers occur at days 7 and 14
      postinfection (p.i.), and infectious HMPV can be recovered from lungs up to day
      60 p.i. In addition, we show that genomic HMPV RNA can be detected in the lungs
      for >/=180 days p.i. by reverse transcription-PCR; however, neither HMPV RNA nor
      infectious virus can be detected in serum, spleen, kidneys, heart, trachea, and
      brain tissue. Lung histopathology revealed prevalent mononuclear cell
      infiltration in the interstitium beginning at day 2 p.i. and peaking at day 4
      p.i. which decreased by day 14 p.i. and was associated with airway remodeling.
      Increased mucus production evident at day 2 p.i. was concordant with increased
      bronchial and bronchiolar inflammation. HMPV-specific antibodies were detected by
      day 14 p.i., neutralizing antibody titers reached >/=6.46 log(2) end-point titers
      by day 28 p.i., and depletion of T cells or NK cells resulted in increased HMPV
      titers in the lungs, suggesting some immune control of viral persistence. This
      study shows that BALB/c mice are amenable for HMPV studies and indicates that
      HMPV persists as infectious virus in the lungs of normal mice for several weeks
      postinfection.

PMID- 15564508
TI  - A dominant role for CD8+-T-lymphocyte selection in simian immunodeficiency virus
      sequence variation.
AB  - CD8(+) T lymphocytes (CD8-TL) select viral escape variants in both human
      immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The
      frequency of CD8-TL viral escape as well as the contribution of escape to overall
      virus diversification has not been assessed. We quantified CD8-TL selection in
      SIV infections by sequencing viral genomes from 35 SIVmac239-infected animals at
      the time of euthanasia. Here we show that positive selection for sequences
      encoding 46 known CD8-TL epitopes is comparable to the positive selection
      observed for the variable loops of env. We also found that >60% of viral
      variation outside of the viral envelope occurs within recognized CD8-TL epitopes.
      Therefore, we conclude that CD8-TL selection is the dominant cause of SIV
      diversification outside of the envelope.

PMID- 15564509
TI  - Clinical latency and reactivation of AIDS-related mycobacterial infections.
AB  - The immune mechanisms associated with the evolution from latent to clinically
      active mycobacterial coinfection in human immunodeficiency virus type 1 (HIV-1)
      infected humans remain poorly understood. Previous work has demonstrated that
      macaques infected with simian immunodeficiency virus (SIVmac) can develop
      persistent Mycobacterium bovis BCG coinfection and a fatal SIV-related
      tuberculosis-like disease by 4 months after BCG inoculation. In the present
      study, SIVmac-infected monkeys that developed clinically quiescent mycobacterial
      infection after BCG inoculation were followed prospectively for the reactivation
      of the BCG and the development of SIV-related tuberculosis-like disease. The
      development of clinically latent BCG coinfection in these SIVmac-infected monkeys
      was characterized by a change from high to undetectable levels of bacterial
      organisms, with or without measurable BCG mRNA expression in lymph node cells.
      The reactivation of clinically latent BCG coinfection and development of SIV
      related tuberculosis-like disease were then observed in these SIVmac-BCG
      coinfected monkeys during a 21-month period of follow-up. The reactivation of SIV
      related tuberculosis-like disease in these animals coincided with a severe
      depletion of CD4 T cells and a loss of BCG-specific T-cell responses.
      Interestingly, bacterial superantigen challenge of the SIVmac-BCG-coinfected
      monkeys resulted in an up-regulation of clinically latent BCG coinfection,
      suggesting that infection with superantigen-producing microbes may increase the
      susceptibility of individuals to the reactivation of AIDS-related mycobacterial
      coinfection. Thus, reactivation of latent mycobacterial infections in HIV-1
      infected individuals may result from a loss of T-cell immunity or from a
      superimposed further compromise of the immune system.

PMID- 15564510
TI  - Definition of sequence requirements for latency-associated nuclear antigen 1
      binding to Kaposi's sarcoma-associated herpesvirus DNA.
AB  - In latent infection, Kaposi's sarcoma-associated herpesvirus (KSHV) latency
      associated nuclear antigen 1 (LANA1)-specific binding to KSHV terminal repeat DNA
      mediates multicopy episome persistence. We now use electrophoretic mobility shift
      assays to investigate LANA1 binding to its 20-bp cognate sequence. Mutations at
      positions 6, 7, and 8 ((6)CCC(8)) severely reduced LANA1 binding, whereas
      mutations at other positions only modestly reduced binding. Since (6)CCC(8) is in
      the 5' half of an inverted repeat sequence, these results are consistent with an
      asymmetric role for the inverted repeat in LANA1 binding.

PMID- 15564511
TI  - Neutralization profiles of newly transmitted human immunodeficiency virus type 1
      by monoclonal antibodies 2G12, 2F5, and 4E10.
AB  - As the AIDS epidemic continues unabated, the development of a human
      immunodeficiency virus (HIV) vaccine is critical. Ideally, an effective vaccine
      should elicit cell-mediated and neutralizing humoral immune responses. We have
      determined the in vitro susceptibility profile of sexually transmitted viruses
      from 91 patients with acute and early HIV-1 infection to three monoclonal
      antibodies, 2G12, 2F5, and 4E10. Using a recombinant virus assay to measure
      neutralization, we found all transmitted viruses were neutralized by 4E10, 80%
      were neutralized by 2F5, and only 37% were neutralized by 2G12. We propose that
      the induction of 4E10-like antibodies should be a priority in designing
      immunogens to prevent HIV-1 infection.

PMID- 15564512
TI  - Overexpression of 7a, a protein specifically encoded by the severe acute
      respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent
      pathway.
AB  - Besides genes that are homologous to proteins found in other coronaviruses, the
      severe acute respiratory syndrome coronavirus genome also contains nine other
      potential open reading frames. Previously, we have characterized the expression
      and cellular localization of two of these "accessory" viral proteins, 3a
      (previously termed U274) and 7a (previously termed U122). In this study, we
      further examined whether they can induce apoptosis, which has been observed
      clinically. We showed that the overexpression of 7a, but not of 3a or the viral
      structural proteins, nucleocapsid, membrane, and envelope, induces apoptosis. 7a
      induces apoptosis via a caspase-dependent pathway and in cell lines derived from
      different organs, including lung, kidney, and liver.

PMID- 15564513
TI  - A period of transient viremia and occult infection precedes persistent viremia
      and antiviral immune responses during multiple low-dose intravaginal simian
      immunodeficiency virus inoculations.
AB  - In rhesus macaques, classic systemic infection, characterized by persistent
      viremia and seroconversion, occurred after multiple low-dose (10(3) 50% tissue
      culture infective doses) intravaginal (IVAG) inoculations with simian
      immunodeficiency virus (SIV) strain SIVmac251. Monkeys developed classic SIV
      infections after a variable number of low-dose IVAG exposures to SIVmac251. Once
      established, the systemic infection was identical to SIV infection following high
      dose IVAG SIV inoculation. However, occult systemic infection characterized by
      transient cell-associated or cell-free viremia consistently occurred early in the
      series of multiple vaginal SIV exposures. Further, antiviral cellular immune
      responses were present prior to the establishment of a classic systemic infection
      in the low-dose vaginal SIV transmission model.

PMID- 15564514
TI  - Association of DC-SIGN promoter polymorphism with increased risk for parenteral,
      but not mucosal, acquisition of human immunodeficiency virus type 1 infection.
AB  - There is considerable debate about the fundamental mechanisms that underlie and
      restrict acquisition of human immunodeficiency virus type 1 (HIV-1) infection. In
      light of recent studies demonstrating the ability of C type lectins to facilitate
      infection with HIV-1, we explored the potential relationship between
      polymorphisms in the DC-SIGN promoter and risk for acquisition of HIV-1 according
      to route of infection. Using samples obtained from 1,611 European-American
      participants at risk for parenteral (n = 713) or mucosal (n = 898) infection, we
      identified single-nucleotide polymorphisms in the DC-SIGN promoter using single
      strand conformation polymorphism. Individuals at risk for parenterally acquired
      infection who had -336C were more susceptible to infection than were persons with
      -336T (odds ratio = 1.87, P = 0.001). This association was not observed in those
      at risk for mucosally acquired infection. A potential role for DC-SIGN specific
      to systemic acquisition and dissemination of infection is suggested.

PMID- 15564515
TI  - Genetic screen for monitoring severe acute respiratory syndrome coronavirus 3C
      like protease.
AB  - A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory
      syndrome. Site-specific proteolysis plays a critical role in regulating a number
      of cellular and viral processes. Since the main protease of SCoV, also termed 3C
      like protease, is an attractive target for drug therapy, we have developed a
      safe, simple, and rapid genetic screen assay to monitor the activity of the SCoV
      3C-like protease. This genetic system is based on the bacteriophage lambda
      regulatory circuit, in which the viral repressor cI is specifically cleaved to
      initiate the lysogenic-to-lytic switch. A specific target for the SCoV 3C-like
      protease, P1/P2 (SAVLQ/SGFRK), was inserted into the lambda phage cI repressor.
      The target specificity of the SCoV P1/P2 repressor was evaluated by coexpression
      of this repressor with a chemically synthesized SCoV 3C-like protease gene
      construct. Upon infection of Escherichia coli cells containing the two plasmids
      encoding the cI. SCoV P1/P2-cro and the beta-galactosidase-SCoV 3C-like protease
      constructs, lambda phage replicated up to 2,000-fold more efficiently than in
      cells that did not express the SCoV 3C-like protease. This simple and highly
      specific assay can be used to monitor the activity of the SCoV 3C-like protease,
      and it has the potential to be used for screening specific inhibitors.

PMID- 15564516
TI  - Variable methylation of the Epstein-Barr virus Wp EBNA gene promoter in B
      lymphoblastoid cell lines.
AB  - During the initial stages of Epstein-Barr virus (EBV) infection of peripheral
      resting B cells, transcription of the six genes encoding the EBV latency
      associated nuclear antigens (EBNAs) is driven from Wp, a promoter that is present
      in multiple copies within the EBV major internal repeat. As infection progresses,
      transcription from Wp is downregulated following upregulation of EBNA gene
      transcription driven from a promoter, Cp, located ca. 3 kb upstream of the first
      copy of Wp. Recently published data have provided evidence that, concomitant with
      the switch in EBNA gene promoter usage, Wp becomes heavily methylated (R. J.
      Tierney et al., J. Virol. 74:10468-10479, 2000). Based on this observation, it
      has been argued that methylation of Wp plays a pivotal role in suppressing Wp
      activity in EBV-immortalized B-lymphoblastoid cell lines (LCLs). Here we present
      data compiled from analyses of Wp methylation in eight randomly selected low
      passage-number B-LCLs. These data demonstrate that there is considerable
      variability in Wp methylation, both between different cell lines and within
      clonal LCLs. Overall, less methylation of Wp was noted in established, low
      passage-number LCLs than was previously observed in bulk cultures of infected B
      cells at days 18 and 21 postinfection. Importantly, the majority of LCLs examined
      harbored both unmethylated and methylated copies of Wp. In addition, all low
      passage-number LCLs examined contained both Cp- and Wp-initiated EBNA
      transcripts, arguing for the presence of some transcriptionally active copies of
      Wp. Taken together, these data argue that other factors, perhaps in conjunction
      with Wp methylation, play a role in suppressing Wp activity in LCLs.

PMID- 15564517
TI  - Infectious molecular clone of a recently transmitted pediatric human
      immunodeficiency virus clade C isolate from Africa: evidence of intraclade
      recombination.
AB  - Although human immunodeficiency virus type 1 (HIV-1) clade C continues to
      dominate the pandemic, only two infectious clade C proviral DNA clones have been
      described (N. Mochizuki, N. Otsuka, K. Matsuo, T. Shiino, A. Kojima, T. Kurata,
      K. Sakai, N. Yamamoto, S. Isomura, T. N. Dhole, Y. Takebe, M. Matsuda, and M.
      Tatsumi, AIDS Res. Hum. Retrovir. 15:1321-1324, 1999; T. Ndung'u, B. Renjifo, and
      M. Essex, J. Virol. 75:4964-4972, 2001). We have generated an infectious
      molecular clone of a pediatric clade C strain, HIV1084i, which was isolated from
      a Zambian infant infected either intrapartum or through breastfeeding. HIV1084i
      is an R5, non-syncytium-inducing isolate that bears all known clade C signatures;
      gag, pol, and env consistently mapped within clade C. Interestingly, gag
      resembled Asian isolates, whereas pol and env resembled African isolates,
      indicating that HIV1084i probably arose from an intraclade recombination. As a
      recently transmitted clade C strain, HIV1084i will be a useful vaccine
      development tool.

PMID- 15564518
TI  - New TAXI-type xylanase inhibitor genes are inducible by pathogens and wounding in
      hexaploid wheat.
AB  - TAXI-I (Triticum aestivum xylanase inhibitor I) is a wheat grain protein that
      inhibits arabinoxylan fragmentation by microbial endo-beta-1,4-xylanases used in
      the food industry. Although TAXI was speculated to be involved in counterattack
      against pathogens, there is actually no evidence to support this hypothesis. We
      have now demonstrated the presence of TAXI family members with isolation of two
      mRNA species, Taxi-III and Taxi-IV. At the nucleotide sequence level, Taxi-III
      and Taxi-IV were 91.7% and 92.0% identical, respectively, to Taxi-I, and Taxi-III
      and Taxi-IV were 96.8% identical. Accumulation of Taxi-III/IV transcripts was
      most evident in roots and older leaves where transcripts of Taxi-I were
      negligible. When challenged by fungal pathogens Fusarium graminearum and Erysiphe
      graminis, the concentrations of Taxi-III/IV transcripts increased significantly.
      In contrast, the increases in Taxi-I transcripts in response to these pathogens
      were rather limited. Both Taxi-I and Taxi-III/IV were strongly expressed in
      wounded leaves. The upstream region of Taxi-III contained W boxes and GCC boxes,
      which are sufficient to confer pathogen and wound inducibility on promoters.
      Recombinant TAXI-III protein inhibited Aspergillus niger and Trichoderma sp.
      xylanases: it was also active against some spelt xylan-induced xylanases of F.
      graminearum. These features suggest that some, but not all, TAXI-type xylanase
      inhibitors have a role in plant defense.

PMID- 15564519
TI  - BLADE-ON-PETIOLE1 encodes a BTB/POZ domain protein required for leaf
      morphogenesis in Arabidopsis thaliana.
AB  - The BLADE-ON-PETIOLE1 (BOP1) gene of Arabidopsis thaliana is required for proper
      leaf morphogenesis. BOP1 regulates leaf differentiation in a proximal-distal
      manner, and represses the expression of three class I knotted-like homeobox
      (knox) genes during leaf formation. Utilizing a map-based approach, we identified
      the molecular nature of the BOP1 gene, which encodes a BTB/POZ domain protein
      with ankyrin repeats. BOP1 is a member of a small gene family in Arabidopsis that
      includes the disease resistance regulatory protein NPR1. Insertions in and around
      BOP1 cause distinct lesions in leaf morphogenesis, revealing complex regulation
      of the locus. BOP1 transcripts are initially detectable in embryos, where they
      specifically localize to the base of the developing cotyledons near the SAM.
      During vegetative development, BOP1 is expressed in young leaf primordia and at
      the base of the rosette leaves on the adaxial side. During reproductive
      development, BOP1 transcripts are detected in young floral buds, and at the base
      of the sepals and petals. Our results indicate that BOP1 encodes a putative
      regulatory protein that modulates meristematic activity at discrete locations in
      developing lateral organs. This is the first report on a plant protein that plays
      a key role in morphogenesis with the distinctive combinatorial architecture of
      the BTB/POZ and ankyrin repeat domains.

PMID- 15564520
TI  - Three types of tobacco calmodulins characteristically activate plant NAD kinase
      at different Ca2+ concentrations and pHs.
AB  - We previously reported that three types of tobacco calmodulin (CaM) isoforms
      originated from 13 genes are differently regulated at the transcript and protein
      levels in response to wounding and tobacco mosaic virus-induced hypersensitive
      reaction (HR); wound-inducible type I and HR-inducible type III levels increased
      after wounding and HR, respectively, while type II, whose expression is
      constitutive and wound responsible, remained unchanged. Here, we show that these
      CaMs differentially activate target enzymes; rat NO synthase was activated most
      effectively by type III, moderately by type I and weakly by type II, and plant
      NAD kinase (NADK) was activated in the inverse order. Furthermore, we found that
      a suitable Ca2+ concentration differs by type; type II activated NADK at lower
      Ca2+ of around 0.1 microM, which is the cytosolic concentration in unstimulated
      cells, type I did so at 1-5 microM, which is the increased Ca2+ concentration in
      stimulated cells, while type III did not at any Ca2+ level. NADK activation was
      highest over a pH range of 7.1-6.8 for which the cytosolic pH reportedly changed
      from 7.5 after being stimulated. Thus, tobacco CaMs, especially type I,
      effectively activate NADK in stimuli-induced conditions.

PMID- 15564521
TI  - The putative glutamate receptor 1.1 (AtGLR1.1) in Arabidopsis thaliana regulates
      abscisic acid biosynthesis and signaling to control development and water loss.
AB  - The involvement of the putative glutamate receptor 1.1 (AtGLR1.1) gene in the
      regulation of abscisic acid (ABA) biosynthesis and signaling was investigated in
      Arabidopsis. Seeds from AtGLR1.1-deficient (antiAtGLR1.1) lines had increased
      sensitivity to exogenous ABA with regard to the effect of the hormone on the
      inhibition of seed germination and root growth. Seed germination, which was
      inhibited by an animal ionotropic glutamate receptor antagonist, 6,7
      dinitroquinoxaline-2,3-[1H,4H]-dione, was restored by co-incubation with an
      inhibitor of ABA biosynthesis, fluridone. These results confirm that germination
      in antiAtGLR1.1 lines was inhibited by increased ABA. When antiAtGLR1.1 and WT
      seeds were co-incubated in fluridone and exogenous ABA, the antiAtGLR1.1 seeds
      were more sensitive to ABA. In addition, the antiAtGLR1.1 lines exhibited altered
      expression of ABA biosynthetic (ABA) and signaling (ABI) genes, when compared
      with WT. Combining the physiological and molecular results suggest that ABA
      biosynthesis and signaling in antiAtGLR1.1 lines are altered. ABA levels in
      leaves of antiAtGLR1.1 lines are higher than those in WT. In addition, the
      antiAtGLR1.1 lines had reduced stomatal apertures, and exhibited enhanced drought
      tolerance due to deceased water loss compared with WT lines. The results from
      these experiments imply that ABA biosynthesis and signaling can be regulated
      through AtGLR1.1 to trigger pre- and post-germination arrest and changes in whole
      plant responses to water stress. Combined with our earlier results, these
      findings suggest that AtGLR1.1 integrates and regulates the different aspects of
      C, N and water balance that are required for normal plant growth and development.

PMID- 15564522
TI  - The rbcX gene product promotes the production and assembly of ribulose-1,5
      bisphosphate carboxylase/oxygenase of Synechococcus sp. PCC7002 in Escherichia
      coli.
AB  - The operon encoding ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in
      the cyanobacterium Synechococcus sp. PCC7002 contains three rbc genes, rbcL, rbcX
      and rbcS, in this order. Introduction of translational frameshift into the rbcX
      gene resulted in a significant decrease in the production of large (RbcL) and
      small (RbcS) subunits of the Rubisco protein in Synechococcus sp. PCC7002 and in
      Escherichia coli. To investigate the function of the rbcX gene product (RbcX), we
      constructed the expression plasmid for the rbcX gene and examined the effects of
      RbcX on the recombinant Rubisco production in Escherichia coli. The coexpression
      experiments revealed that RbcX had marked effects on the production of large and
      small subunits of Rubisco without any significant influence on the mRNA level of
      rbc genes and/or the post-translational assembly of the Rubisco protein. The
      present rbcX coexpression system provides a novel and useful method for
      investigating the Rubisco maturation pathway.

PMID- 15564523
TI  - Ethylene synthesis and auxin augmentation in pistil tissues are important for egg
      cell differentiation after pollination in maize.
AB  - The role of ethylene and auxin in stigma-to-ovule signalling was investigated in
      maize (Zea mays L.). Maturation of the egg cells in an ear was stimulated before
      actual fertilization by the application of fresh pollen grains or quartz sand to
      fully receptive stigmas. Ethylene emission by maize ears increased in response to
      those treatments. Silks and ovaries were involved in ethylene synthesis after
      pollen or sand was shed over the silks. The content of ethylene precursor [1
      aminocyclopropane-1-carboxylic acid (ACC)] increased in both pistil parts soon
      after pollination. ACC rise was delayed by 4 h in the ovaries, and by 8 h in the
      silks after mock-pollination with sand. The auxin level increased rapidly in the
      silks and ovaries after pollination, and it was very high in the pollinated silks
      due to the high indole-3-acetic acid (IAA) content of pollen grains. IAA rise
      also appeared in the silks and ovaries after treatment with sand but it was
      delayed by 8 h. Application of ACC (10 microM) or IAA (6 microM) solutions to non
      pollinated silks stimulated maturation of the egg cells. Moreover, the response
      of the egg cells to pollination was cancelled by l-alpha-(2-aminoethoxyvinyl)
      glycine, alpha-aminoisobutyric acid or 2,3,5-triiodobenzoic acid applied to the
      silks before pollination. Thus ethylene synthesis and polar auxin transport in
      the silks pollinated with fresh pollen were necessary to evoke accelerated
      differentiation of the egg cells in maize ovules. Differences in pistil responses
      found between true- and mock-pollination suggest that signalling pathways are at
      least partially different for the reception of pollen grains and sand crystals on
      maize stigma.

PMID- 15564524
TI  - Identification of major proteins in maize egg cells.
AB  - In most flowering plants, the female gametophyte develops in an ovule deeply
      embedded in the ovary. Through double fertilization, the egg cell fuses with the
      sperm cell, resulting in a zygote, which develops into the embryo. In the present
      study, we analyzed egg cell lysates by polyacrylamide gel electrophoresis and
      subsequent mass spectrometry-based proteomics technology, and identified major
      protein components expressed in the egg cell. The identified proteins included
      three cytosolic enzymes of the glycolytic pathway, glyceraldehyde-3-phosphate
      dehydrogenase, 3-phosphoglycerate kinase and triosephosphate isomerase, two
      mitochondrial proteins, the ATP synthase beta-subunit and an adenine nucleotide
      transporter, and annexin p35. In addition, expression levels of these proteins in
      the egg cell were compared with those in the early embryo, the central cell and
      the suspension cell. Annexin p35 was highly expressed only in the egg cell, and
      glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase and the
      adenine nucleotide transporter were expressed at higher levels in egg cells than
      in central and cultured cells. These results indicate that annexin p35 in the egg
      cell and zygote is involved in the exocytosis of cell wall materials, which is
      induced by a fertilization-triggered increase in cytosolic Ca2+ levels, and that
      the egg cell is rich in an enzyme subset for the energy metabolism.

PMID- 15564525
TI  - Transgenic tobacco (Nicotiana tabacum L.) plants with increased expression levels
      of mitochondrial NADP+-dependent isocitrate dehydrogenase: evidence implicating
      this enzyme in the redox activation of the alternative oxidase.
AB  - Many metabolic reactions are coupled to NADPH in the mitochondrial matrix,
      including those involved in thiol group reduction. One enzyme linked to such
      processes is mitochondrial NADP+-dependent isocitrate dehydrogenase (mtICDH; EC
      1.1.1.42), although the precise role of this enzyme is not yet known. Previous
      work has implicated mtICDH as part of a biochemical mechanism to reductively
      activate the alternative oxidase (AOX). We have partially purified mtICDH from
      tobacco (Nicotiana tabacum L. cv. Petit Havana SR1) cell suspension cultures and
      localized this to a 46-kDa protein on SDS-PAGE, which was verified by peptide
      sequencing. In the inflorescence of the aroid Sauromatum guttatum Schott (voodoo
      lily), mtICDH appears to be developmentally regulated, presenting maximal
      specific activity during the thermogenic period of anthesis when the capacity for
      AOX respiration is also at its peak. Transgenic tobacco plants were generated
      that overexpress mtICDH and lines were obtained that demonstrated up to a 7-fold
      increase in mtICDH activity. In isolated mitochondria, this resulted in a
      measurable increase in the reductive activation of AOX in comparison with wild
      type. When examined in planta in response to citrate feeding, a strong conversion
      of AOX from its oxidized to its reduced form was observed in the transgenic line.
      These data support the hypothesis that mtICDH may be a regulatory switch involved
      in tricarboxylic acid cycle flux and the reductive modulation of AOX.

PMID- 15564526
TI  - Enhancement of cyclic electron flow around PSI at high light and its contribution
      to the induction of non-photochemical quenching of chl fluorescence in intact
      leaves of tobacco plants.
AB  - Non-photochemical quenching (NPQ) of Chl fluorescence is a mechanism for
      dissipating excess photon energy and is dependent on the formation of a DeltapH
      across the thylakoid membranes. The role of cyclic electron flow around
      photosystem I (PSI) (CEF-PSI) in the formation of this DeltapH was elucidated by
      studying the relationships between O2-evolution rate [V(O2)], quantum yield of
      both PSII and PSI [Phi(PSII) and Phi(PSI)], and Chl fluorescence parameters
      measured simultaneously in intact leaves of tobacco plants in CO2-saturated air.
      Although increases in light intensity raised V(O2) and the relative electron
      fluxes through both PSII and PSI [Phi(PSII) x PFD and Phi(PSI) x PFD] only
      Phi(PSI) x PFD continued to increase after V(O2) and Phi(PSII) x PFD became light
      saturated. These results revealed the activity of an electron transport reaction
      in PSI not related to photosynthetic linear electron flow (LEF), namely CEF-PSI.
      NPQ of Chl fluorescence drastically increased after Phi(PSII) x PFD became light
      saturated and the values of NPQ correlated positively with the relative activity
      of CEF-PSI. At low temperatures, the light-saturation point of Phi(PSII) x PFD
      was lower than that of Phi(PSI) x PFD and NPQ was high. On the other hand, at
      high temperatures, the light-dependence curves of Phi(PSII) x PFD and Phi(PSI) x
      PFD corresponded completely and NPQ was not induced. These results indicate that
      limitation of LEF induced CEF-PSI, which, in turn, helped to dissipate excess
      photon energy by driving NPQ of Chl fluorescence.

PMID- 15564527
TI  - Bioconcentration mechanism of selenium by a coccolithophorid, Emiliania huxleyi.
AB  - We investigated the uptake and bioconcentration of the essential element selenium
      by a coccolithophorid, Emiliania huxleyi, using [75Se]selenite. The time course
      of 75Se uptake showed a biphasic pattern, namely a primary phase and a subsequent
      secondary phase. The primary and secondary phases are due to a rapid selenite
      uptake process that attained a stationary level within 2 min and a slow Se
      accumulation process that continued at a constant rate for 4 h or longer,
      respectively. Kinetic analysis revealed that the selenite uptake process consists
      of two components, one saturable and one linearly related to substrate
      concentration. The Km of the saturable component was 29.8 nM selenite; the uptake
      activity of this component was suppressed by inhibitors of ATP biogenesis,
      suggesting that selenite uptake is driven by a high-affinity, active transport
      system. During a 6-h incubation of cells with [75Se]selenite, 70% of the
      intracellular 75Se was incorporated into low-molecular-mass compounds (LMCs), and
      17% was incorporated into proteins, but [75Se]selenite was barely detectable. A
      pulse-chase experiment demonstrated that the 75Se that had accumulated in LMCs
      was transferred into proteins. When the syntheses of amino acids and proteins
      were each separately inhibited, 75Se incorporation into LMCs and proteins was
      decreased. These results suggest that E. huxleyi rapidly absorbs selenite,
      filling a small intracellular pool. Then, Se-containing LMCs are immediately
      synthesized from the selenite, creating a pool of LMCs that are then metabolized
      to selenoproteins.

PMID- 15564528
TI  - Ten rice peroxidases redundantly respond to multiple stresses including infection
      with rice blast fungus.
AB  - Class III plant peroxidases are believed to function in diverse physiological
      processes including disease resistance and wound response, but predicted low
      substrate specificities and the presence of 70 or more isoforms have made it
      difficult to define a specific physiological function(s) for each gene. To select
      pathogen-responsive POX genes, we analyzed the expression profiles of 22 rice POX
      genes after infection with rice blast fungus. The expression of 10 POX genes
      among the 22 genes was induced after fungal inoculation in both compatible and
      incompatible hosts. Seven of the 10 POX genes were expressed at higher levels in
      the incompatible host than in the compatible host 6-24 h after inoculation by
      which time no fungus-induced lesions have appeared. Organ-specific expression and
      stress-induced expression by wounding and treatment with probenazole, an
      agrichemical against blast fungus, jasmonic acid, salicylic acid and 1
      aminocyclopropane-1-carboxylate, a precursor of ethylene, indicated that rice
      POXs have individual characteristics and can be classified into several types. A
      comparison of the amino acid sequences of POXs showed that multiple isoforms with
      a high sequence similarity respond to stress in different or similar ways. Such
      redundant responses of POX genes may guarantee POX activities that are necessary
      for self-defense in plant tissues against environmental stresses including
      pathogen infection.

PMID- 15564529
TI  - The GAOLAOZHUANGREN1 gene encodes a putative glycosyltransferase that is critical
      for normal development and carbohydrate metabolism.
AB  - Glycosyltransferases are enzymes that catalyze the attachment of a sugar molecule
      to specific acceptor molecules. These enzymes have been shown to play important
      roles in a number of biological processes. Whereas a large number of putative
      glycosyltransferase genes have been identified by genomic sequencing, the
      functions of most of these genes are unknown. Here we report the characterization
      of an Arabidopsis mutant, designated gaolaozhuangren1 (glz1), which is allelic to
      parvus characterized recently. The glz1 mutant exhibited a reduced plant stature,
      reduced size of organs in the shoot and dark-green leaves, indicating an
      important role of GLZ1 gene in normal development. The earliest GLZ1 expression
      appears at the shoot apical region of 4-d-old seedlings, which coincides with the
      onset of the glz1 morphological phenotypes. GLZ1 is expressed in a tissue
      specific and developmentally regulated manner, predominantly in the stem and
      silique, and moderately in the flower. GLZ1 expression is strong in the midrib of
      rosette and cauline leaves; however, its expression was not detectable in the
      midrib of the cotyledon. Further analyses revealed that carbohydrate composition
      and distribution were aberrant in the glz1 mutant. These, together with the GLZ1
      expression pattern, suggest a requirement for the GLZ1 function in normal sink
      source transition during plant development.

PMID- 15564530
TI  - Phloem unloading in developing walnut fruit is symplasmic in the seed pericarp
      and apoplasmic in the fleshy pericarp.
AB  - The sieve element-companion cell (SE-CC) complex of the sepal bundles feeding the
      fleshy pericarp of developing walnut (Juglans regia L.) fruit is structurally
      symplasmically isolated, but the SE-CC complex of the minor ventral carpellary
      bundles located in the seed pericarp and feeding the seed is structurally
      symplasmically connected to its adjacent parenchyma cells. 14C-autoradiography
      indicated that the phloem of both the sepal and carpellary bundles was functional
      for unloading. Confocal laser scanning microscopy imaging of carboxyfluorescein
      unloading showed that the dye is confined to the phloem strands of the sepal
      bundles in the fleshy pericarp, but released from the phloem strands of the minor
      ventral carpellary bundles into the surrounding parenchyma cells in the seed
      pericarp. A 60-kDa acid invertase was immunolocalized to the cell wall of SE-CC
      complex and parenchyma cells in both the fleshy and seed pericarp. These data
      provide clear evidence for an apoplasmic phloem unloading pathway in the fleshy
      pericarp and a predominant symplasmic phloem unloading pathway parallel with a
      possible apoplasmic path as suggested by the presence of the extracellular
      invertase in the seed pericarp. A model of complex phloem unloading pathways in
      developing walnut fruit has been proposed.

PMID- 15564531
TI  - The relation of starch phosphorylases to starch metabolism in wheat.
AB  - Tissues of wheat (Triticum aestivum L., var. Star) exhibit three starch
      phosphorylase activity forms resolved by non-denaturing polyacrylamide gel
      affinity electrophoresis (P1, P2 and P3). Compartmentation analysis of young leaf
      tissues showed that P3 is plastidic, whereas P1 and P2 are cytosolic. P1 exhibits
      a strong binding affinity to immobilized glycogen upon electrophoresis, whereas
      P2 and the chloroplastic P3 do not. Cytosolic leaf phosphorylase was purified to
      homogeneity by affinity chromatography. The single polypeptide product
      constituted both the P1 and P2 activity forms. Probes for the detection of
      phosphorylase transcripts were derived from cDNA sequences of cytosolic and
      plastidic phosphorylases, and these-together with activity assays and a cytosolic
      phosphorylase-specific antiserum-were used to monitor phosphorylase expression in
      leaves and seeds. Mature leaves contained only plastidic phosphorylase, which was
      also strongly evident in the endosperm of developing seeds at the onset of
      reserve starch accumulation. Germinating seeds contained only cytosolic
      phosphorylase, which was restricted to the embryo. Plastidic phosphorylase thus
      appears to be associated with transitory leaf starch metabolism and with the
      initiation of seed endosperm reserve starch accumulation, but it plays no role in
      the degradation of the reserve starch. Cytosolic phosphorylase may be involved in
      the processing of incoming carbohydrate during rapid tissue growth.

PMID- 15564532
TI  - Isolation and characterization of novel mutants affecting the abscisic acid
      sensitivity of Arabidopsis germination and seedling growth.
AB  - To gain more insight into ABA signaling mechanisms, we conducted genetic screens
      searching for mutants with altered ABA response in germination and post
      germination growth. We isolated seven putative ABA-hypersensitive Arabidopsis
      mutants and named them ABA-hypersensitive germination (ahg). These mutants
      exhibited diminished germination or growth ability on medium supplemented with
      ABA. We further studied four of them: ahg1, ahg2, ahg3 and ahg4. Mapping
      suggested that they were new ABA-hypersensitive loci. Characterization showed
      that all of them had enhanced sensitivity to salinity and high osmotic stress in
      germinating seeds, whereas they each had distinct sugar responses. RT-PCR
      experiments showed that the expression patterns of the ABA-inducible genes RAB18,
      AtEm1, AtEm6 and ABI5 in germinating seeds were affected by these four ahg
      mutations, whereas those of ABI3 and ABI4 were not. ahg4 displayed slightly
      increased mRNA levels of several ABA-inducible genes upon ABA treatment. By
      contrast, ahg1 had no clear ABA-hypersensitive phenotypes in adult plants despite
      its strong phenotype in germination. These results suggest that ahg1, ahg2, ahg3
      and ahg4 are novel ABA-hypersensitive mutants representing distinct components in
      the ABA response.

PMID- 15564533
TI  - Silencing of the aleurone-specific Ltp2-gus gene in transgenic rice is reversed
      by transgene rearrangements and loss of aberrant transcripts.
AB  - An Ltp2 promoter was isolated from barley as an aleurone-specific promoter, and
      its tissue specificity was maintained in transgenic rice. Expression of the Ltp2
      gus gene in rice could be detected by X-gluc staining of the seeds. Previously,
      we reported the isolation of silenced plants in the R2 generation and the
      involvement of antisense gus transcripts in aleurone-specific Ltp2-gus gene
      silencing in transgenic rice, the L3.3 line. In the current study, we analyzed
      the L0.1 line, a sibling of the L3.3 line, and the partially revertant line from
      the L0.1 line accompanied by a transgene structural change. Strong silencing of
      the Ltp2-gus gene was detected over five generations in the L0.1 line. DNA and
      RNA analysis revealed that there were incomplete transgenes and that several
      aberrant RNAs that carried an antisense gus region were expressed in the L0.1
      line. Determination of the transgene structure in the L0.1 line revealed that the
      partial antisense gus gene and the partial Ltp2 promoter region fused to the Ltp2
      promoter were lacking in the revertants. RNA analysis demonstrated that the
      antisense gus and the promoter transcripts were produced and found in the poly(A)
      fraction. Results of these analyses suggested that the observed aberrant
      transcripts, including antisense and promoter transcripts, were associated with
      Ltp2-gus silencing in the L0.1 line.

PMID- 15564534
TI  - The maize O2 and PBF proteins act additively to promote transcription from
      storage protein gene promoters in rice endosperm cells.
AB  - A transient expression assay system was employed to investigate the possible use
      of the maize Opaque 2 (O2) and prolamin box binding factor (PBF) proteins as
      transcriptional activators of rice and wheat storage protein gene promoters. When
      assayed in developing rice endosperm cells, either O2 or PBF alone could increase
      transcription from the promoter of the rice glutelin gene, Gt1. However, mutant
      forms of O2 and PBF that are defective in DNA binding could not. Co-transfection
      with both transcriptional activators resulted in an additive increase in
      transactivation of the Gt1 promoter. Co-bombardment of a Gt1::GUS construct with
      plasmids expressing the DNA binding domains of O2 and PBF in antisense
      orientation resulted in a decrease of GUS expression below background levels.
      Similar stimulatory and additive effects of O2 and PBF could be observed on the
      promoters from other storage protein genes including rice globulin (Glb),
      prolamins (RP6 and PG5a) and a wheat glutenin (Bx7). However, responsiveness of
      the promoters from non-storage protein genes like rice actin and CaMV 35S to O2
      and PBF was insignificant. Our results indicate that the maize O2 and PBF
      proteins can act singly or additively as effective stimulators of heterologous
      storage protein promoters in developing rice endosperm cells. These data support
      the use of well-characterized transcription factors from maize as an effective
      means of increasing the expression level of recombinant proteins in developing
      rice seeds.

PMID- 15564535
TI  - Gene expression profiles of cold-stored and fresh pollen to investigate pollen
      germination and growth.
AB  - In lily (Lilium longiflorum cv. Avita) pollen cold-stored (-20 degrees C) for 2
      months, typical in vitro germination/growth was delayed by about 1 h compared
      with fresh pollen. We hypothesized that some proteins and mRNAs stored in mature
      pollen were degraded during storage periods and that re-synthesis of them was
      essential to resume normal germination and growth. Cold-stored and fresh pollen
      grains were used to investigate the regulatory mechanism of pollen germination
      and tube growth in terms of both total protein profile and gene expression. Total
      protein profiles of cold-stored pollen differed qualitatively and quantitatively
      from fresh pollen. Actinomycin D significantly inhibited both germination and
      tube growth of cold-stored pollen and later tube growth of fresh pollen but had
      no effect on fresh pollen germination and early tube growth. Suppression
      subtractive hybridization screening revealed 99 cDNAs enriched in fresh mature
      pollen, and 22 were selected for further characterization. Most of these 22 cDNAs
      gradually disappeared during cold storage, but full recovery was achieved by
      incubating the cold-stored pollen in culture medium for 2 h. Because of different
      sensitivities to cold storage and actinomycin D, the transcripts were divided
      into three groups according to their possible roles in pollen germination and
      tube growth. Several cDNAs encoding novel proteins showed pollen-specific
      expression patterns and may participate in drought tolerance (an Na+/H+
      antiporter), endomembrane trafficking (DnaJ), division of the generative cell
      (Sgt1), pollen wall precursor uptake from stylar exudate (an Na+/myoinositol
      symporter) and chemotropism of the pollen tube (peptide transporter) during
      pollination.

PMID- 15564536
TI  - Spatial and temporal tracing of vessel differentiation in young Arabidopsis
      seedlings by the expression of an immature tracheary element-specific promoter.
AB  - The vascular system is a complex tissue composed of several vascular cell types.
      However, little is known about the differentiation process of each vascular cell
      in situ. In this study, we found that the expression of the Zinnia cysteine
      protease 4 (ZCP4) promoter is restricted to only immature tracheary elements
      (TEs) in situ. Therefore, we monitored the early TE differentiation process in
      young Arabidopsis seedlings using a fusion gene of the ZCP4 promoter and the beta
      glucuronidase gene as a molecular marker. This approach revealed unique processes
      of vessel differentiation during early seedling development, in which
      discontinuous initiation of vessel element differentiation occurs at distinct
      regions, followed by the simultaneous differentiation of protoxylem vessels and
      bidirectional differentiation of metaxylem vessels to form a vessel in the plant
      body.

PMID- 15564537
TI  - Ornithine decarboxylase gene (CaODC1) is specifically induced during TMV-mediated
      but salicylate-independent resistant response in hot pepper.
AB  - A gene encoding putative ornithine decarboxylase (ODC) has been isolated by
      differential screening of a cDNA library from the resistant hot pepper (Capsicum
      annuum L.) inoculated with avirulent tobacco mosaic virus (TMV) pathotype P0. In
      hot pepper plants, transcripts of the CaODC1 (C. annuum ODC1) gene started to
      accumulate at 24 h post-inoculation of TMV-P0 and the signal was spread
      systemically. The transcript level of CaODC1 was increased rapidly in a hot
      pepper resistant to Xanthomonas campestris pv. vesicatoria (Xcv) but not in a
      susceptible hot pepper after inoculation. These results suggest possible role(s)
      for CaODC1 in plant defense against a broad range of pathogens including viruses
      and bacteria.

PMID- 15564538
TI  - Images in clinical medicine. Double aortic arch diagnosed by magnetic resonance
      imaging.

PMID- 15564539
TI  - The cord-blood-bank controversies.

PMID- 15564540
TI  - Westward ho?--The spread of West Nile virus.

PMID- 15564541
TI  - Health care reform in France--the birth of state-led managed care.

PMID- 15564542
TI  - Prolonging patency--choosing coronary bypass grafts.

PMID- 15564543
TI  - Outcomes after transplantation of cord blood or bone marrow from unrelated donors
      in adults with leukemia.
AB  - BACKGROUND: Data regarding the outcome of cord-blood transplantation in adults
      are scant, despite the fact that these grafts are increasingly used in adults.
      METHODS: We compared the outcomes of the transplantation of hematopoietic stem
      cells from unrelated donors in adults with leukemia who had received cord blood
      that was mismatched for one HLA antigen (34 patients) or two antigens (116
      patients), bone marrow that had one HLA mismatch (83 patients), and HLA-matched
      bone marrow (367 patients). We used Cox proportional-hazards models to analyze
      the data. RESULTS: Cord-blood recipients were younger and more likely to have
      advanced leukemia than were bone marrow recipients, and they received lower doses
      of nucleated cells. Hematopoietic recovery was slower with transplantation of
      mismatched bone marrow and cord blood than with matched marrow transplantations.
      Acute graft-versus-host disease (GVHD) was more likely to occur after mismatched
      marrow transplantation, and chronic GVHD was more likely to occur after cord
      blood transplantation. The rates of treatment-related mortality, treatment
      failure, and overall mortality were lowest among patients who received matched
      marrow transplants. Patients who received mismatched bone marrow transplants and
      those who received mismatched cord-blood transplants had similar rates of
      treatment-related mortality (P=0.96), treatment failure (P=0.69), and overall
      mortality (P=0.62). There were no differences in the rate of recurrence of
      leukemia among the groups. There were no differences in outcome after cord-blood
      transplantation between patients with one HLA mismatch and those with two HLA
      mismatches. CONCLUSIONS: HLA-mismatched cord blood should be considered an
      acceptable source of hematopoietic stem-cell grafts for adults in the absence of
      an HLA-matched adult donor.

PMID- 15564544
TI  - Transplants of umbilical-cord blood or bone marrow from unrelated donors in
      adults with acute leukemia.
AB  - BACKGROUND: Promising results of cord-blood transplants from unrelated donors
      have been reported in adults. METHODS: We compared outcomes in 682 adults with
      acute leukemia who received a hematopoietic stem-cell transplant from an
      unrelated donor: 98 received cord blood and 584 received bone marrow. The
      transplantations were performed from 1998 through 2002 and reported to Eurocord
      and the European Blood and Marrow Transplant Group. RESULTS: Recipients of cord
      blood were younger than recipients of bone marrow (median, 24.5 vs. 32 years of
      age; P<0.001), weighed less (median, 58 vs. 68 kg; P<0.001), and had more
      advanced disease at the time of transplantation (52 percent vs. 33 percent,
      P<0.001). All marrow transplants were HLA matched, whereas 94 percent of cord
      blood grafts were HLA mismatched (P<0.001). The median number of nucleated cells
      that were infused was 0.23x10(8) per kilogram of the recipient's body weight for
      cord blood and 2.9x10(8) per kilogram for bone marrow (P<0.001). Multivariate
      analysis showed lower risks of grade II, III, or IV acute graft-versus-host
      disease (GVHD) after cord-blood transplantation (relative risk, 0.57; 95 percent
      confidence interval, 0.37 to 0.87; P=0.01), but neutrophil recovery was
      significantly delayed (relative risk, 0.49; 95 percent confidence interval, 0.41
      to 0.58; P<0.001). The incidence of chronic GVHD, transplantation-related
      mortality, relapse rate, and leukemia-free survival were not significantly
      different in the two groups. CONCLUSIONS: Cord blood from an unrelated donor is
      an alternative source of hematopoietic stem cells for adults with acute leukemia
      who lack an HLA-matched bone marrow donor.

PMID- 15564545
TI  - A randomized comparison of radial-artery and saphenous-vein coronary bypass
      grafts.
AB  - BACKGROUND: In the past decade, the radial artery has frequently been used for
      coronary bypass surgery despite concern regarding the possibility of graft spasm.
      Graft patency is a key predictor of long-term survival. We therefore sought to
      determine the relative patency rate of radial-artery and saphenous-vein grafts in
      a randomized trial in which we controlled for bias in the selection of patients
      and vessels. METHODS: We enrolled 561 patients at 13 centers. The left internal
      thoracic artery was used to bypass the anterior circulation. The radial-artery
      graft was randomly assigned to bypass the major vessel in either the inferior
      (right coronary) territory or the lateral (circumflex) territory, with the
      saphenous-vein graft used for the opposing territory (control). The primary end
      point was graft occlusion, determined by angiography 8 to 12 months
      postoperatively. RESULTS: Angiography was performed at one year in 440 patients:
      8.2 percent of radial-artery grafts and 13.6 percent of saphenous-vein grafts
      were completely occluded (P=0.009). Diffuse narrowing of the graft (the
      angiographic "string sign") was present in 7.0 percent of radial-artery grafts
      and only 0.9 percent of saphenous-vein grafts (P=0.001). The absence of severe
      native-vessel stenosis was associated with an increased risk of occlusion of the
      radial-artery graft and diffuse narrowing of the graft. Harvesting of the radial
      artery was well tolerated. CONCLUSIONS: Radial-artery grafts are associated with
      a lower rate of graft occlusion at one year than are saphenous-vein grafts.
      Because the patency of radial-artery grafts depends on the severity of native
      vessel stenosis, such grafts should preferentially be used for target vessels
      with high-grade lesions.

PMID- 15564546
TI  - Hypertensive retinopathy.

PMID- 15564547
TI  - Images in clinical medicine. Cholelithiasis.

PMID- 15564548
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 36-2004. A 23-day-old infant with hypospadias and failure to
      thrive.

PMID- 15564549
TI  - Cord-blood transplantation in patients with leukemia--a real alternative for
      adults.

PMID- 15564550
TI  - The family history--more important than ever.

PMID- 15564551
TI  - Breast cancer--loss of PTEN predicts resistance to treatment.

PMID- 15564552
TI  - Influenza vaccination with 1/10th the full dose.

PMID- 15564553
TI  - Peginterferon plus ribavirin for hepatitis C in HIV-infected patients.

PMID- 15564554
TI  - Recombinant human leptin in women with hypothalamic amenorrhea.

PMID- 15564555
TI  - Methylprednisolone, valacyclovir, or both for vestibular neuritis.

PMID- 15564556
TI  - Treatment of von Willebrand's Disease.

PMID- 15564557
TI  - Acute renal failure and sepsis.

PMID- 15564558
TI  - Medical mystery--the answer.

PMID- 15564559
TI  - Pay by the pound. Added weight might take a toll on the brain.

PMID- 15564560
TI  - Heads and tails.Less-active tumor suppressor paradoxically promotes both
      longevity and cancer in humans.

PMID- 15564561
TI  - Young at heart.Life-extending mutation preserves fly hearts.

PMID- 15564562
TI  - Nuclear hormone receptors, metabolism, and aging: what goes around comes around.
      Transcription factors link lipid metabolism and aging-related processes.
AB  - Previous studies have linked the mysterious and inevitable process of aging to
      essential processes such as metabolism, maturation, and fecundity. Each of these
      processes is controlled to a large extent by nuclear hormone receptors (NHRs).
      NHRs also play important roles in the control of periodical processes, the most
      recently implicated being circadian rhythm. This Review stresses the mounting
      evidence for tight relationships between each of these NHR-regulated processes
      and the processes of aging.

PMID- 15564563
TI  - Another new kinase targets troponin I.

PMID- 15564564
TI  - Regulation of vascular calcification by osteoclast regulatory factors RANKL and
      osteoprotegerin.
AB  - Vascular calcification often occurs with advancing age, atherosclerosis, various
      metabolic disorders such as diabetes mellitus and end-stage renal disease, or in
      rare genetic diseases, leading to serious clinical consequences. Such
      mineralization can occur at various sites (cardiac valves, arterial intima or
      media, capillaries), involve localized or diffuse widespread calcification, and
      result from numerous causes that provoke active inflammatory and osteogenic
      processes or disordered mineral homeostasis. Although valuable research has
      defined many key factors and cell types involved, surprising new insights
      continue to arise that deepen our understanding and suggest novel research
      directions or strategies for clinical intervention in calcific vasculopathies.
      One emerging area in vascular biology involves the RANKL/RANK/OPG system,
      molecules of the tumor necrosis factor-related family recently discovered to be
      critical regulators of immune and skeletal biology. Evidence is accumulating that
      such signals may be expressed, regulated, and function in vascular physiology and
      pathology in unique ways to promote endothelial cell survival, angiogenesis,
      monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and
      calcification. Concerted research efforts are greatly needed to understand these
      potential roles, clarify whether RANKL (receptor activator of nuclear factor
      kappaB ligand) promotes and osteoprotegerin (OPG) protects against vascular
      calcification, define how OPG genetic polymorphisms relate to cardiovascular
      disease, and learn whether elevated serum OPG levels reflect endothelial
      dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important
      and complex links between the vascular, skeletal, and immune systems. Thus, these
      molecules may play a central role in regulating the development of vascular
      calcification coincident with declines in skeletal mineralization with age,
      osteoporosis, or disease.

PMID- 15564565
TI  - ACE and subarachnoid hemorrhage: strategies for genetics of stroke.

PMID- 15564566
TI  - Contrast ultrasound techniques in the detection and quantification of patent
      foramen ovale: myth versus reality.

PMID- 15564567
TI  - Nicotinamide attenuates focal ischemic brain injury: meta-analysis or mechanism
      of protection.

PMID- 15564568
TI  - Intravenous magnesium for neuroprotection in acute stroke: clinical hope versus
      basic neuropharmacology.

PMID- 15564569
TI  - Editorial comment--A mercy to victims of cerebrovascular diseases.

PMID- 15564573
TI  - Visual experience regulates transient expression and dendritic localization of
      fragile X mental retardation protein.
AB  - Fragile X syndrome is the most common form of inherited mental retardation and is
      caused by the loss of function of the Fragile X mental retardation protein
      (FMRP). FMRP is an RNA binding protein thought to play a key role in protein
      synthesis-dependent synaptic plasticity. The regulation of FMRP expression itself
      is also likely to be an important control point in this process. Here we used
      dark-reared/light-exposed rats to determine the role of experience in regulating
      FMRP levels in the visual cortex. We find that FMRP levels increase in the cell
      bodies and dendrites of visual cortical neurons after as little as 15 min of
      light exposure. Remarkably, FMRP expression in these neurons returns to baseline
      levels by 30 min of light exposure. These changes were post-transcriptional
      because the FMR1 mRNA levels remained constant over this time period. A transient
      increase in FMRP levels was also observed in synaptic fractions prepared from
      visual cortices of light-exposed animals. In contrast, alpha-calcium/calmodulin
      dependent kinase II expression showed a sustained upregulation under these
      conditions. Finally, the increase in FMRP expression was inhibited by blockade of
      NMDA receptors. This tight temporal-spatial regulation suggests that FMRP plays a
      dynamic role in a distinct epoch of experience-dependent synaptic plasticity.

PMID- 15564574
TI  - Calcium-independent calcium/calmodulin-dependent protein kinase II in the adult
      Drosophila CNS enhances the training of pheromonal cues.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the CNS
      and is crucial for cellular and behavioral plasticity. It is thought that the
      ability of CaMKII to autophosphorylate and become Ca2+ independent allows it to
      act as a molecular memory switch. We have shown previously that inhibition of
      Drosophila CaMKII leads to impaired performance in the courtship conditioning
      associative memory assay, but it was unknown whether the constitutive form of the
      kinase had a special role in learning. In this study, we use a tripartite
      transgenic system combining GAL4/UAS with the tetracycline-off system to
      spatially and temporally manipulate levels of Ca2+-independent CaMKII activity in
      Drosophila. We find an enhancement of information processing during the training
      period with Ca2+-independent, but not Ca2+-dependent, CaMKII. During training,
      control animals have a lag before active suppression of courtship begins. Animals
      expressing Ca2+-independent CaMKII have no lag, implying that there is a
      threshold level of Ca2+-independent activity that must be present to suppress
      courtship. This is the first demonstration, in any organism, of enhanced
      behavioral plasticity with overexpression of constitutively active CaMKII.
      Anatomical studies indicate that transgene expression in antennal lobes and
      extrinsic mushroom body neurons drives this behavioral enhancement.
      Interestingly, immediate memory was unaffected by expression of T287D CaMKII in
      mushroom bodies, although previous studies have shown that CaMKII activity is
      required in this brain region for memory formation. These results suggest that
      the biochemical mechanisms of CaMKII-dependent memory formation are threshold
      based in only a subset of neurons.

PMID- 15564575
TI  - Induction of deltaFosB in reward-related brain structures after chronic stress.
AB  - Acute and chronic stress differentially regulate immediate-early gene (IEG)
      expression in the brain. Although acute stress induces c-Fos and FosB, repeated
      exposure to stress desensitizes the c-Fos response, but FosB-like
      immunoreactivity remains high. Several other treatments differentially regulate
      IEG expression in a similar manner after acute versus chronic exposure. The form
      of FosB that persists after these chronic treatments has been identified as
      DeltaFosB, a splice variant of the fosB gene. This study was designed to
      determine whether the FosB form induced after chronic stress is also DeltaFosB
      and to map the brain regions and identify the cell populations that exhibit this
      effect. Western blotting, using an antibody that recognizes all Fos family
      members, revealed that acute restraint stress caused robust induction of c-Fos
      and full-length FosB, as well as a small induction of DeltaFosB, in the frontal
      cortex (fCTX) and nucleus accumbens (NAc). The induction of c-Fos (and to some
      extent full-length FosB) was desensitized after 10 d of restraint stress, at
      which point levels of DeltaFosB were high. A similar pattern was observed after
      chronic unpredictable stress. By use of immunohistochemistry, we found that
      chronic restraint stress induced DeltaFosB expression predominantly in the fCTX,
      NAc, and basolateral amygdala, with lower levels of induction seen elsewhere.
      These findings establish that chronic stress induces DeltaFosB in several
      discrete regions of the brain. Such induction could contribute to the long-term
      effects of stress on the brain.

PMID- 15564576
TI  - Lateral hypothalamic signaling mechanisms underlying feeding stimulation:
      differential contributions of Src family tyrosine kinases to feeding triggered
      either by NMDA injection or by food deprivation.
AB  - In rats, feeding can be triggered experimentally using many approaches. Included
      among these are (1) food deprivation and (2) acute microinjection of the
      neurotransmitter l-glutamate (Glu) or its receptor agonist NMDA into the lateral
      hypothalamic area (LHA). Under both paradigms, the NMDA receptor (NMDA-R) within
      the LHA appears critically involved in transferring signals encoded by Glu to
      stimulate feeding. However, the intracellular mechanisms underlying this signal
      transfer are unknown. Because protein-tyrosine kinases (PTKs) participate in NMDA
      R signaling mechanisms, we determined PTK involvement in LHA mechanisms
      underlying both types of feeding stimulation through food intake and biochemical
      measurements. LHA injections of PTK inhibitors significantly suppressed feeding
      elicited by LHA NMDA injection (up to 69%) but only mildly suppressed deprivation
      feeding (24%), suggesting that PTKs may be less critical for signals underlying
      this feeding behavior. Conversely, food deprivation but not NMDA injection
      produced marked increases in apparent activity for Src PTKs and in the expression
      of Pyk2, an Src-activating PTK. When considered together, the behavioral and
      biochemical results demonstrate that, although it is easier to suppress NMDA
      elicited feeding by PTK inhibitors, food deprivation readily drives PTK activity
      in vivo. The latter result may reflect greater PTK recruitment by
      neurotransmitter receptors, distinct from the NMDA-R, that are activated during
      deprivation-elicited but not NMDA-elicited feeding. These results also
      demonstrate how the use of only one feeding stimulation paradigm may fail to
      reveal the true contributions of signaling molecules to pathways underlying
      feeding behavior in vivo.

PMID- 15564578
TI  - Estrogen receptor (ER)beta isoforms rather than ERalpha regulate corticotropin
      releasing hormone promoter activity through an alternate pathway.
AB  - The hypothalamic-pituitary-adrenal axis regulates mammalian stress responses by
      secreting glucocorticoids. The magnitude of the response is in part determined by
      gender, for in response to a given stressor, circulating glucocorticoids reach
      higher levels in female rats than in males. This gender difference could result
      from estrogen regulation of the corticotropin-releasing hormone (CRH) promoter
      via either of its receptors: estrogen receptor (ER)alpha or ERbeta.
      Immunocytochemistry revealed that a subset (12%) of medial parvocellular CRH
      neurons in the rat hypothalamus contain ERbeta but not ERalpha. To determine
      whether ERs could regulate CRH promoter activity, we cotransfected cells with a
      CRH promoter construct and either ERalpha or individual ERbeta isoforms. ERalpha
      weakly stimulated CRH promoter transcriptional activity in a ligand-independent
      manner. Conversely, all ERbeta isoforms tested stimulated CRH promoter activity
      with different ligand profiles. ERbeta1 and ERbeta2delta3 displayed constitutive
      activity (ERbeta1 more than ERbeta2delta3). Ligand-dependent activity of beta
      isoforms 1 and 2 was altered by an Exon3 splice variant (delta3) or by the
      additional 18 amino acids in the ligand-binding domain of ERbeta2 isoforms.
      Lastly, we suggest that ER regulation of CRH takes place through an alternate
      pathway, one that requires protein-protein interactions with other transcription
      factors or their associated complexes. However, a pure ER-activator protein-1
      alternate pathway does not appear to be involved.

PMID- 15564577
TI  - Peroxynitrite-induced neuronal apoptosis is mediated by intracellular zinc
      release and 12-lipoxygenase activation.
AB  - Peroxynitrite toxicity is a major cause of neuronal injury in stroke and
      neurodegenerative disorders. The mechanisms underlying the neurotoxicity induced
      by peroxynitrite are still unclear. In this study, we observed that TPEN
      [N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine], a zinc chelator, protected
      against neurotoxicity induced by exogenous as well as endogenous
      (coadministration of NMDA and a nitric oxide donor, diethylenetriamine NONOate)
      peroxynitrite. Two different approaches to detecting intracellular zinc release
      demonstrated the liberation of zinc from intracellular stores by peroxynitrite.
      In addition, we found that peroxynitrite toxicity was blocked by inhibitors of 12
      lipoxygenase (12-LOX), p38 mitogen-activated protein kinase (MAPK), and caspase-3
      and was associated with mitochondrial membrane depolarization. Inhibition of 12
      LOX blocked the activation of p38 MAPK and caspase-3. Zinc itself induced the
      activation of 12-LOX, generation of reactive oxygen species (ROS), and activation
      of p38 MAPK and caspase-3. These data suggest a cell death pathway triggered by
      peroxynitrite in which intracellular zinc release leads to activation of 12-LOX,
      ROS accumulation, p38 activation, and caspase-3 activation. Therefore, therapies
      aimed at maintaining intracellular zinc homeostasis or blocking activation of 12
      LOX may provide a novel avenue for the treatment of inflammation, stroke, and
      neurodegenerative diseases in which the formation of peroxynitrite is thought to
      be one of the important causes of cell death.

PMID- 15564579
TI  - Personality predicts brain responses to cognitive demands.
AB  - Eysenck (1981) proposed that the personality dimension of introversion-
      extraversion (E) reflects individual differences in a cortical arousal system
      modulated by reticulothalamic- cortical pathways: it is chronically more active
      in introverts relative to extraverts and influences cognitive performance in
      interaction with task parameters. A circuit with connections to this system,
      including the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate (AC)
      cortex, has been identified in studies applying functional magnetic resonance
      imaging (fMRI) to a broad range of cognitive tasks. We examined the influence of
      E, assessed with the Eysenck Personality Questionnaire-Revised (Eysenck and
      Eysenck, 1991), in fMRI activity during an "n-back" task involving four memory
      loads (0-, 1-, 2-, and 3-back) and a rest condition in healthy men. To confirm
      the specificity of E effects, we also examined the effects of neuroticism and
      psychoticism (P) scores. We observed that, as predicted by Eysenck's model, the
      higher the E score, the greater the change in fMRI signal from rest to the 3-back
      condition in the DLPFC and AC. In addition, E scores were negatively associated
      with resting fMRI signals in the thalamus and Broca's area extending to
      Wernicke's area, supporting the hypothesized (negative) relationship between E
      and resting arousal. P scores negatively correlated with resting fMRI signal in
      the globus pallidus-putamen, extending previous findings of a negative
      relationship of schizotypy to striatal activity seen with older neuroimaging
      modalities to fMRI. These observations suggest that individual differences affect
      brain responses during cognitive activity and at rest and provide evidence for
      the hypothesized neurobiological basis of personality.

PMID- 15564580
TI  - Intracerebral transplantation of adult mouse neural progenitor cells into the
      Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology.
AB  - Niemann-Pick disease is caused by a genetic deficiency in acid sphingomyelinase
      (ASM) leading to the intracellular accumulation of sphingomyelin and cholesterol
      in lysosomes. In the present study, we evaluated the effects of direct
      intracerebral transplantation of neural progenitor cells (NPCs) on the brain
      storage pathology in the ASM knock-out (ASMKO) mouse model of Type A Niemann-Pick
      disease. NPCs derived from adult mouse brain were genetically modified to express
      human ASM (hASM) and were transplanted into multiple regions of the ASMKO mouse
      brain. Transplanted NPCs survived, migrated, and showed region-specific
      differentiation in the host brain up to 10 weeks after transplantation (the
      longest time point examined). In vitro, gene-modified NPCs expressed up to 10
      times more and released five times more ASM activity into the culture media
      compared with nontransduced NPCs. In vivo, transplanted cells expressed hASM at
      levels that were barely detectable by immunostaining but were sufficient for
      uptake and cross-correction of host cells, leading to reversal of distended
      lysosomal pathology and regional clearance of sphingomyelin and cholesterol
      storage. Within the host brain, the area of correction closely overlapped with
      the distribution of the hASM-modified NPCs. No correction of pathology occurred
      in brain regions that received transplants of nontransduced NPCs. These results
      indicate that the presence of transduced NPCs releasing low levels of hASM within
      the ASMKO mouse brain is necessary and sufficient to reverse lysosomal storage
      pathology. Potentially, NPCs may serve as a useful gene transfer vehicle for the
      treatment of CNS pathology in other lysosomal storage diseases and
      neurodegenerative disorders.

PMID- 15564581
TI  - Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of
      inhibition in prefrontal cortex.
AB  - Typically, D1 and D2 dopamine (DA) receptors exert opposing actions on
      intracellular signaling molecules and often have disparate physiological effects;
      however, the factors determining preferential activation of D1 versus D2
      signaling are not clear. Here, in vitro patch-clamp recordings show that DA
      concentration is a critical determinant of D1 versus D2 signaling in prefrontal
      cortex (PFC). Low DA concentrations (<500 nm) enhance IPSCs via D1 receptors,
      protein kinase A, and cAMP. Higher DA concentrations (>1 microm) decrease IPSCs
      via the following cascade: D2-->G(i)-->platelet-derived growth factor receptor-->
      increase phospholipase C--> increase IP3--> increase Ca2+--> decrease dopamine
      and cAMP-regulated phosphoprotein-32--> increase protein phosphatase 1/2A-->
      decrease GABA(A). Blockade of any molecule in the D2-linked pathway reveals a D1
      mediated increase in IPSCs, suggesting that D1 effects are occluded at higher DA
      concentrations by this D2-mediated pathway. Thus, DA concentration, by acting
      through separate signaling cascades, may determine the relative amount of
      cortical inhibition and thereby differentially regulate the tuning of cortical
      networks.

PMID- 15564582
TI  - Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium
      mediated signaling.
AB  - In neurons, neurogranin (Ng) binds calmodulin (CaM), and its binding affinity is
      reduced by increasing Ca2+, phosphorylation by PKC, or oxidation by oxidants. Ng
      concentration in the hippocampus of adult mice varied broadly (Ng+/+, 160-370 and
      Ng+/-, approximately 70-230 pmol/mg); the level in Ng+/+ mice is one of the
      highest among all neuronal CaM-binding proteins. Among Ng+/- mice, but less
      apparent in Ng+/+, a significant relationship existed between their hippocampal
      levels of Ng and performances in the Morris water maze. Ng-/- mice performed
      poorly in this task; they also displayed deficits in high-frequency-induced long
      term potentiation (LTP) in area CA1 of hippocampal slices, whereas low-frequency
      induced long-term depression was enhanced. Thus, compared with Ng+/+ mice, the
      frequency-response curve of Ng-/- shifted to the right. Paired-pulse facilitation
      and synaptic fatigue during prolonged stimulation at 10 Hz (900 pulses) were
      unchanged in Ng-/- slices, indicating their normal presynaptic function.
      Measurements of Ca2+ transients in CA1 pyramidal neurons after weak and strong
      tetanic stimulations (100 Hz, 400 and 1000 msec, respectively) revealed a
      significantly greater intracellular Ca2+ ([Ca2+]i) response in Ng+/+ compared
      with Ng-/- mice, but the decay time constants did not differ. The diminished Ca2+
      dynamics in Ng-/- mice are a likely cause of their decreased propensity to
      undergo LTP. Thus, Ng may promote a high [Ca2+]i by a "mass-action" mechanism;
      namely, the higher the Ng concentration, the more Ng-CaM complexes will be
      formed, which effectively raises [Ca2+]i at any given Ca2+ influx. This mechanism
      provides potent signal amplification in enhancing synaptic plasticity as well as
      learning and memory.

PMID- 15564583
TI  - Interactions between GABAergic and cholinergic processes in the nucleus pontis
      oralis: neuronal mechanisms controlling active (rapid eye movement) sleep and
      wakefulness.
AB  - The cholinergic system within the nucleus pontis oralis (NPO) of the pontine
      tegmentum is critically involved in the generation of active (rapid eye movement)
      sleep. Previously, we demonstrated that a GABAergic system in the NPO also plays
      an important role in the control of the behavioral states of wakefulness as well
      as active sleep. The present study examined interactions between these two
      neuronal systems vis-a-vis the occurrence of these behavioral states.
      Accordingly, cholinergic and GABAergic agonists and antagonists were injected
      into the NPO, and their combined effects on sleep and waking states of chronic,
      unanesthetized cats were examined. Microinjections of carbachol into the NPO
      elicited active sleep with a short latency. However, a preinjection of muscimol
      (a GABA(A) agonist) completely blocked the active sleep-inducing effects of
      carbachol. The induction of active sleep by carbachol was also suppressed by a
      subsequent injection of muscimol. On the other hand, the microinjection of
      scopolamine (a muscarinic receptor antagonist) did not block the induction of
      active sleep by bicuculline (a GABA(A) antagonist). We conclude that the
      excitatory cholinergic control of NPO neurons that are involved in the generation
      of active sleep is gated by a pontine GABAergic system that exerts its effects
      postsynaptically by inhibiting NPO neurons, resulting in the suppression of
      active sleep and the generation of wakefulness. In the absence of the activation
      of this GABAergic gating mechanism, active sleep occurs. These results reveal
      that specific interactions between cholinergic and GABAergic processes in the NPO
      play a critical role in the generation of active sleep and wakefulness.

PMID- 15564584
TI  - Ethanol potentiation of GABAergic synaptic transmission may be self-limiting:
      role of presynaptic GABA(B) receptors.
AB  - Ethanol enhances GABAergic synaptic inhibition, and this interaction contributes
      to many of the behavioral and cognitive effects of this drug. Most studies
      suggest that ethanol enhances GABAergic neurotransmission via an allosteric
      potentiation of the postsynaptic GABA(A) receptors that mediate fast synaptic
      inhibition in the mammalian CNS. Despite widespread acceptance of this
      hypothesis, direct support for such a mechanism has been difficult to obtain.
      Ethanol does not enhance GABA(A) receptor function in all brain regions or under
      all experimental conditions, and factors responsible for this variability remain
      mostly unknown. Notably, blockade of GABA(B) receptors dramatically enhances
      ethanol potentiation of hippocampal GABA(A) IPSPs and IPSCs, suggesting that some
      unknown GABA(B) receptor mechanism limits the overall potentiating effect of
      ethanol on GABAergic synapses. In this study, we demonstrate that, at perisomatic
      synapses in the rat hippocampus, ethanol enhances presynaptic GABA(B)
      autoreceptor function and that this interaction reduces the overall potentiating
      effect of ethanol at these synapses. We further show that ethanol significantly
      elevates basal presynaptic GABA(B) receptor tone, possibly via an increase in
      spontaneous GABA release, and that pretreatment with a subthreshold concentration
      of the GABA(B) receptor agonist baclofen blocks ethanol but not flunitrazepam or
      pentobarbital potentiation of GABA(A) IPSCs. These data suggest that an
      interaction between ethanol and presynaptic GABA(B) autoreceptor activity
      regulates the ethanol sensitivity of GABAergic synapses. Given that the in vitro
      ethanol sensitivity of these synapses correlates with in vivo ethanol
      responsiveness in a number of rodent lines, our data further suggest that
      presynaptic GABA(B) receptor activity may play a role in regulating behavioral
      sensitivity to ethanol.

PMID- 15564585
TI  - Decreased synaptic activity shifts the calcium dependence of release at the
      mammalian neuromuscular junction in vivo.
AB  - We examined the mechanism underlying increased quantal content after block of
      activity at the mouse neuromuscular junction in vivo. We found that, when quantal
      content was measured in solution containing normal extracellular calcium, block
      of activity had no effect on either quantal content or the response to repetitive
      stimulation. However, when quantal content was measured in low extracellular
      calcium, there was a large increase in quantal content after block of activity.
      The increase in quantal content was accompanied by increased depression during
      repetitive stimulation. The explanation for these findings was that there was a
      shift in the calcium dependence of release after block of activity that
      manifested as an increase in probability of release in low extracellular calcium.
      Block of presynaptic P/Q channels eliminated the increase in probability of
      release. We propose that activity-dependent regulation of presynaptic calcium
      entry may contribute to homeostatic regulation of quantal content.

PMID- 15564586
TI  - Malfunction of respiratory-related neuronal activity in Na+, K+-ATPase alpha2
      subunit-deficient mice is attributable to abnormal Cl- homeostasis in brainstem
      neurons.
AB  - Na+, K+-ATPase 2 subunit gene (Atp1a2) knock-out homozygous mice (Atp1a2-/-) died
      immediately after birth resulting from lack of breathing. The respiratory-related
      neuron activity in Atp1a2-/- was investigated using a brainstem-spinal cord en
      bloc preparation. The respiratory motoneuron activity recorded from the fourth
      cervical ventral root (C4) was defective in Atp1a2-/- fetuses of embryonic day
      18.5. The C4 response to electrical stimulation of the ventrolateral medulla
      (VLM) recovered more slowly in Atp1a2-/- than in wild type during superfusion
      with Krebs' solution, consistent with the high extracellular GABA in brain of
      Atp1a2-/-. Lack of inhibitory neural activities in VLM of Atp1a2-/- was observed
      by optical recordings. High intracellular Cl- concentrations in neurons of the
      VLM of Atp1a2-/- were detected in gramicidin-perforated patch-clamp recordings.
      The alpha2 subunit and a neuron-specific K-Cl cotransporter KCC2 were
      coimmunoprecipitated in a purified synaptic membrane fraction of wild-type
      fetuses. Based on these results, we propose a model for functional coupling
      between the Na+, K+-ATPase alpha2 subunit and KCC2, which excludes Cl- from the
      cytosol in respiratory center neurons.

PMID- 15564587
TI  - Control of attention shifts between vision and audition in human cortex.
AB  - Selective attention contributes to perceptual efficiency by modulating cortical
      activity according to task demands. Visual attention is controlled by activity in
      posterior parietal and superior frontal cortices, but little is known about the
      neural basis of attentional control within and between other sensory modalities.
      We examined human brain activity during attention shifts between vision and
      audition. Attention shifts from vision to audition caused increased activity in
      auditory cortex and decreased activity in visual cortex and vice versa,
      reflecting the effects of attention on sensory representations. Posterior
      parietal and superior prefrontal cortices exhibited transient increases in
      activity that were time locked to the initiation of voluntary attention shifts
      between vision and audition. These findings reveal that the attentional control
      functions of posterior parietal and superior prefrontal cortices are not limited
      to the visual domain but also include the control of crossmodal shifts of
      attention.

PMID- 15564588
TI  - Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated
      suppression of excitation in dopamine neurons.
AB  - Endocannabinoids form a novel class of retrograde messengers that modulate short-
      and long-term synaptic plasticity. Depolarization-induced suppression of
      excitation (DSE) and inhibition (DSI) are the best characterized transient forms
      of endocannabinoid-mediated synaptic modulation. Stimulation protocols consisting
      of long-lasting voltage steps to the postsynaptic cell are routinely used to
      evoke DSE-DSI. Little is known, however, about more physiological conditions
      under which these molecules are released in vitro. Moreover, the occurrence in
      vivo of such forms of endocannabinoid-mediated modulation is still controversial.
      Here we show that physiologically relevant patterns of synaptic activity induce a
      transient suppression of excitatory transmission onto dopamine neurons in vitro.
      Accordingly, in vivo endocannabinoids depress the increase in firing and bursting
      activity evoked in dopamine neurons by prefrontal cortex stimulation. This
      phenomenon is selectively mediated by the endocannabinoid 2-arachidonoyl-glycerol
      (2-AG), which activates presynaptic cannabinoid type 1 receptors. 2-AG synthesis
      involves activation of metabotropic glutamate receptors and Ca2+ mobilization
      from intracellular stores. These findings indicate that dopamine neurons release
      2-AG to shape afferent activity and ultimately their own firing pattern. This
      novel endocannabinoid-mediated self-regulatory role of dopamine neurons may bear
      relevance in the pathogenesis of neuropsychiatric disorders such as schizophrenia
      and addiction.

PMID- 15564589
TI  - Activation of the cGMP pathway in dopaminergic structures reduces cocaine-induced
      EGR-1 expression and locomotor activity.
AB  - Nitric oxide (NO) and the C-type natriuretic peptide (CNP) exert their action on
      brain via the cGMP signaling pathway. NO, by activating soluble guanylyl cyclase,
      and CNP, by stimulating membrane-bound guanylyl cyclase, cause intracellular
      increases of cGMP, activating cGMP-dependent protein kinases (PKGs). We show here
      that injection of CNP into the rat ventral tegmental area strongly reduced
      cocaine-induced egr-1 expression in the nucleus accumbens in a dose-dependent
      manner. The effect of CNP was reversed by the previous injection of a selective
      PKG inhibitor, KT5823. Activation of PKG by 8-bromo-cGMP reduced, like CNP,
      cocaine-induced gene transcription in dopaminergic structures. To confirm the
      involvement of PKG, this was overexpressed in either the mesencephalon or the
      caudate-putamen. Using the polyethyleneimine delivery system, an active protein
      was expressed by injecting a plasmid vector containing the human PKG-Ialpha cDNA.
      PKG was overexpressed in dopaminergic and GABAergic neurons when the plasmid was
      injected in the ventral tegmental area, whereas overexpression was observed in
      medium spiny GABAergic neurons and in both cholinergic and GABAergic interneurons
      when the PKG vector was injected into the caudate-putamen. Activation of the
      overexpressed PKG reduced cocaine-induced egr-1 expression in dopaminergic
      structures and affected behavior (i.e., locomotor activity). These effects were
      again reversed by previous injection of the selective PKG inhibitor. The current
      data suggest that NO and the neuropeptide CNP are potential regulators of cocaine
      related effects on behavior.

PMID- 15564590
TI  - A role of ventral tegmental area glutamate in contextual cue-induced relapse to
      heroin seeking.
AB  - The environmental context previously associated with opiate use plays an
      important role in human relapse, but the neuronal mechanisms involved in context
      induced drug relapse are not known. Using a rat relapse model, we determined the
      effect of a group II metabotropic glutamate receptor agonist [LY379268 ((-)-2-oxa
      4-aminobicylco hexane-4,6-dicarboxylic acid)] on contextual cue-induced
      reinstatement of heroin seeking. LY379268, which acts centrally to reduce evoked
      glutamate release, was injected systemically or directly into the ventral
      tegmental area (VTA), a brain area involved in opiate reward and conditioned drug
      effects. Rats were trained to self-administer intravenous heroin for 12 d; drug
      infusions were paired with a discrete tone-light cue. Subsequently, lever
      pressing was extinguished in the presence of the discrete cue in a context that
      differed from the drug self-administration context in terms of visual, auditory,
      tactile, and circadian cues. After extinction of lever responding, LY379268 was
      injected systemically or into the VTA, and nonreinforced responding was
      determined in the extinction context or the drug context. Exposure to the heroin
      associated context induced robust reinstatement of drug seeking, and this effect
      was attenuated by systemic or intra-VTA injections of LY379268. Results indicate
      that glutamate transmission in the VTA plays an important role in contextual cue
      induced relapse to heroin seeking.

PMID- 15564591
TI  - Encoding of natural scene movies by tonic and burst spikes in the lateral
      geniculate nucleus.
AB  - The role of the lateral geniculate nucleus (LGN) of the thalamus in visual
      encoding remains an open question. Here, we characterize the function of tonic
      and burst spikes in cat LGN X-cells in signaling features of natural stimuli. A
      significant increase in bursting was observed during natural stimulation
      (relative to white noise stimulation) and was linked to the strong correlation
      structure of the natural scene movies. Burst responses were triggered by specific
      stimulus events consisting of a prolonged inhibitory stimulus, followed by an
      excitatory stimulus, such as the movement of an object into the receptive field.
      LGN responses to natural scene movies were predicted using an integrate-and-fire
      (IF) framework and compared with experimentally observed responses. The standard
      IF model successfully predicted LGN responses to natural scene movies during
      tonic firing, indicating a linear relationship between stimulus and response.
      However, the IF model typically underpredicted the LGN response during periods of
      bursting, indicating a nonlinear amplification of the stimulus in the actual
      response. The addition of a burst mechanism to the IF model was necessary to
      accurately predict the entire LGN response. These results suggest that LGN bursts
      are an important part of the neural code, providing a nonlinear amplification of
      stimulus features that are typical of the natural environment.

PMID- 15564592
TI  - Brain-derived neurotrophic factor regulation of retinal growth cone filopodial
      dynamics is mediated through actin depolymerizing factor/cofilin.
AB  - The molecular mechanisms by which neurotrophins regulate growth cone motility are
      not well understood. This study investigated the signaling involved in
      transducing BDNF-induced increases of filopodial dynamics. Our results indicate
      that BDNF regulates filopodial length and number through a Rho kinase-dependent
      mechanism. Additionally, actin depolymerizing factor (ADF)/cofilin activity is
      necessary and sufficient to transduce the effects of BDNF. Our data indicate that
      activation of ADF/cofilin mimics the effects of BDNF on filopodial dynamics,
      whereas ADF/cofilin inactivity blocks the effects of BDNF. Furthermore, BDNF
      promotes the activation of ADF/cofilin by reducing the phosphorylation of
      ADF/cofilin. Although inhibition of myosin II also enhances filopodial length,
      our results indicate that BDNF signaling is independent of myosin II activity and
      that the two pathways result in additive effects on filopodial length. Thus,
      filopodial extension is regulated by at least two independent mechanisms. The
      BDNF-dependent pathway works via regulation of ADF/cofilin, independently of
      myosin II activity.

PMID- 15564593
TI  - Regulation of HCN channel surface expression by a novel C-terminal protein
      protein interaction.
AB  - Hyperpolarization-activated cation currents (I(h)) are carried by channels
      encoded by a family of four genes (HCN1-4) that are differentially expressed
      within the brain in specific cellular and subcellular compartments. HCN1 shows a
      high level of expression in apical dendrites of cortical pyramidal neurons and in
      presynaptic terminals of cerebellar basket cells, structures with a high density
      of I(h). Expression of I(h) is also regulated by neuronal activity. To isolate
      proteins that may control HCN channel expression or function, we performed yeast
      two-hybrid screens using the C-terminal cytoplasmic tails of the HCN proteins as
      bait. We identified a brain-specific protein, which has been previously termed
      TRIP8b (for TPR-containing Rab8b interacting protein) and PEX5Rp (for Pex5p
      related protein), that specifically interacts with all four HCN channels through
      a conserved sequence in their C-terminal tails. In situ hybridization and
      immunohistochemistry show that TRIP8b and HCN1 are colocalized, particularly
      within dendritic arbors of hippocampal CA1 and neocortical layer V pyramidal
      neurons. The dendritic expression of TRIP8b in layer V pyramidal neurons is
      disrupted after deletion of HCN1 through homologous recombination, demonstrating
      a key in vivo interaction between HCN1 and TRIP8b. TRIP8b dramatically alters the
      trafficking of HCN channels heterologously expressed in Xenopus oocytes and human
      embryonic kidney 293 cells, causing a specific decrease in surface expression of
      HCN protein and I(h) density, with a pronounced intracellular accumulation of HCN
      protein that is colocalized in discrete cytoplasmic clusters with TRIP8b.
      Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases
      native I(h) density. These data suggest a possible role for TRIP8b in regulating
      HCN channel density in the plasma membrane.

PMID- 15564594
TI  - Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying
      neurons in adult rodent brain.
AB  - Recent studies suggest that postmitotic neurons can reenter the cell cycle as a
      prelude to apoptosis after brain injury. However, most dying neurons do not pass
      the G1/S-phase checkpoint to resume DNA synthesis. The specific factors that
      trigger abortive DNA synthesis are not characterized. Here we show that the
      combination of hypoxia and ischemia induces adult rodent neurons to resume DNA
      synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and
      expression of G1/S-phase cell cycle transition markers. After hypoxia-ischemia,
      the majority of BrdU- and neuronal nuclei (NeuN)-immunoreactive cells are also
      terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling
      (TUNEL)-stained, suggesting that they undergo apoptosis. BrdU+ neurons, labeled
      shortly after hypoxia-ischemia, persist for >5 d but eventually disappear by 28
      d. Before disappearing, these BrdU+/NeuN+/TUNEL+ neurons express the
      proliferating cell marker Ki67, lose the G1-phase cyclin-dependent kinase (CDK)
      inhibitors p16INK4 and p27Kip1 and show induction of the late G1/S-phase CDK2
      activity and phosphorylation of the retinoblastoma protein. This contrasts to
      kainic acid excitotoxicity and traumatic brain injury, which produce TUNEL
      positive neurons without evidence of DNA synthesis or G1/S-phase cell cycle
      transition. These findings suggest that hypoxia-ischemia triggers neurons to
      reenter the cell cycle and resume apoptosis-associated DNA synthesis in brain.
      Our data also suggest that the demonstration of neurogenesis after brain injury
      requires not only BrdU uptake and mature neuronal markers but also evidence
      showing absence of apoptotic markers. Manipulating the aberrant apoptosis
      associated DNA synthesis that occurs with hypoxia-ischemia and perhaps
      neurodegenerative diseases could promote neuronal survival and neurogenesis.

PMID- 15564595
TI  - Reduced uteroplacental perfusion alters uterine arcuate artery function in the
      pregnant Sprague-Dawley rat.
AB  - Evidence continues to implicate reduced placental perfusion as the cause of
      preeclampsia, initiating a sequence of events leading to altered vascular
      function and hypertension. The present study was designed to determine the
      influence of reduced uteroplacental perfusion pressure (RUPP) on the
      responsiveness of uterine arcuate resistance arteries. A condition of RUPP was
      surgically induced in pregnant Sprague-Dawley rats on Gestational Day 14. On
      Gestational Day 20, uterine arcuate arteries were mounted on a small-vessel wire
      myograph and challenged with incremental concentrations of vasoconstrictors and
      vasorelaxants for measurement of isometric tension. Compared to the sham-operated
      controls, uterine arteries from the RUPP group demonstrated an increased maximal
      tension in response to phenylephrine (P < 0.01); potassium chloride at 30 mM (P <
      0.05), 60 mM (P < 0.01), and 120 mM (P < 0.01); and angiotensin II (P < 0.05). In
      arteries from the RUPP and sham-operated control groups, endothelium-dependent
      relaxation in response to acetylcholine (P < 0.05) and calcium ionophore (A23187;
      P < 0.05) was significantly reduced in the RUPP group compared to the sham
      operated controls. Fetal growth indices, including litter size, fetal weight, and
      placental weight, were significantly reduced in the RUPP group compared to sham
      operated controls, which is consistent with significant growth restriction. Data
      suggest that RUPP promotes hyperresponsiveness and impaired endothelium-dependent
      relaxation in uterine arcuate arteries, leading to intrauterine fetal growth
      restriction.

PMID- 15564596
TI  - Relationship between low-molecular-weight insulin-like growth factor-binding
      proteins, caspase-3 activity, and oocyte quality.
AB  - Bovine follicular atresia is associated with the apoptosis of granulosa cells and
      the subsequent loss of oocyte competence through the reduction of cellular
      contact (e.g., gap junctions). Several components of the insulin-like growth
      factor (IGF) system are thought to affect follicular atresia. Whereas the IGF
      binding proteins (IGFBPs) are present in varying quantities throughout follicular
      development, IGFBP-5 appears to be present only during atresia, in parallel with
      its regulation in other tissue remodeling systems. However, to our knowledge, no
      connection has yet been made between atresia, low-molecular-weight IGFBP content,
      and oocyte quality in the bovine ovary. Caspases are actively involved in ovarian
      follicular atresia, and apoptosis in antral follicles is caspase-3-dependent.
      Hence, the aim of the present study was to investigate the use of these factors
      in the assessment of oocyte quality and developmental potential. Oocytes were
      aspirated, morphologically classified, and individually matured in vitro. The
      follicular fluid and granulosa cells of these follicles were analyzed for IGFBP
      profile and caspase-3 activity, respectively. A significant correlation was found
      between the presence of low-molecular-weight IGFBPs in bovine follicular fluid
      and caspase-3 activity of granulosa cells isolated from individual follicles. The
      highest percentage of development to the blastocyst stage was observed in oocytes
      from slightly atretic follicles. This group of oocytes contained an equal
      proportion of oocytes at grades 1-3. These data demonstrate that low-molecular
      weight IGFBP profile is a more reliable method than the traditional morphological
      assessment of oocytes and can be used as an effective marker of developmentally
      competent oocytes. Importantly, these results have implications for the use of
      noninvasive follicular fluid markers in the selection of competent oocytes to
      improve outcomes of in vitro fertilization.

PMID- 15564597
TI  - Expression of estrogen receptors-alpha and -beta in the pregnant ovine uterine
      artery endothelial cells in vivo and in vitro.
AB  - Estrogen is recognized to be one of the driving forces in increases in uterine
      blood flow through both rapid and delayed actions via binding to its receptors,
      ER alpha and ER beta at the uterine artery (UA) wall, and especially in UA
      endothelium (UAE). However, information regarding estrogen receptor (ER)
      expression in UAE is limited. This study was designed to test whether ERs are
      expressed in UAE in vivo, and if they are, whether these receptors are maintained
      in cultured UA endothelial cells (UAECs) in vitro. By using immunohistochemical
      and Western blot analyses, we clearly demonstrated ER alpha and ER beta protein
      expression in pregnant (Days 120-130) sheep UA and UAE in vivo and as well as
      cultured UAECs in vitro. Reverse transcription-polymerase chain reaction (RT-PCR)
      amplified both ER alpha and ER beta mRNAs in UA, UAE, and UAECs. Of interest, a
      truncated ER beta (ER beta2) variant due to a splicing deletion of exon 5 of the
      ER beta gene was detected in these cells. Quantitative RT-PCR analysis revealed
      that ER alpha mRNA levels are approximately 8-fold (P < 0.01) higher than that of
      ER beta in UAECs, indicating that ER alpha may play a more important role than ER
      beta in the UAEC responses to estrogen. Fluorescence immunolabeling analysis
      showed that ER alpha is present in both nuclei and plasma membranes in UAECs, and
      the latter is also colocalized with caveolin-1. The membrane and nuclear ER alpha
      presumably participate in rapid and delayed responses, respectively, to estrogen
      on UAE. Taken together, our data demonstrated that UAE is a direct target of
      estrogen actions and that the UAEC culture model we established is suitable for
      dissecting estrogen actions on UAE.

PMID- 15564598
TI  - Apoptosis contributes to vascular lumen formation and vascular branching in human
      placental vasculogenesis.
AB  - Placental vasculogenesis consists of several stages, including appearance of
      hemangioblasts and angiogenic cell islands, setting up a primitive vascular
      network, and transition from vasculogenesis to sprouting and nonsprouting
      angiogenesis. In the present study, we hypothesized that placental vasculogenesis
      and angiogenesis require apoptosis during the formation of primitive vascular
      pattern, vessel elongation, and angiogenic branching. Vasculogenesis and
      apoptotic cells were identified using CD31 immunohistochemistry, hematoxylin
      eosin (H-E) staining, CD31-TUNEL double-labeling, and transmission-electron
      microscopy (TEM). No TUNEL-positive cell was detected in angiogenic cell islands;
      however, several TUNEL-positive cells were observed during the primitive lumen
      formation. Interestingly, some of the stromal cells located between vasculogenic
      areas during the endothelial tube elongation and angiogenic branching also were
      TUNEL-positive. The presence of morphological aspects of apoptosis, such as
      nuclear shrinkage and nuclear bodies (apoptotic bodies), also was confirmed in H
      E-stained and TEM-depicted sections. Quantitative analysis showed that higher
      ratios for apoptotic cells were found in the core stroma of villi among the
      vascular branching areas and in the primitive capillary lumen compared to
      angiogenic cell cords and vasculatures with advanced lumens (P < 0.05). In
      conclusion, our results suggest that apoptosis likely is involved in the
      physiologic mechanisms of placental vasculogenesis and angiogenesis, such as
      lumen formation and angiogenic branching.

PMID- 15564599
TI  - Molecular characterization of equine P-selectin (CD62P) and its regulation in
      ovarian follicles during the ovulatory process.
AB  - Ovulation is accompanied by a marked infiltration of leukocytes into thecal
      layers after the gonadotropin surge. P-selectin is known to play a critical role
      in the initial steps of leukocyte recruitment from the bloodstream during
      inflammation. Thus, the objective was to investigate the potential regulation of
      P-selectin by gonadotropins in equine preovulatory follicles. The full-length
      equine P-selectin cDNA was cloned by a combination of reverse transcription
      polymerase chain reaction (RT-PCR) and 5'- and 3'-rapid amplification of cDNA
      ends. Results showed that equine P-selectin cDNA encodes an 829-amino acid
      protein that is highly conserved when compared to the human protein (80%
      identity). Semiquantitative RT-PCR/Southern blot analyses were performed to study
      the regulation of P-selectin transcript in preovulatory follicles isolated during
      estrus at 0, 12, 24, 30, 33, 36, and 39 h after an ovulatory dose of hCG
      (ovulation occurs between 39 and 42 h post-hCG in this model). Results showed
      that levels of P-selectin mRNA remained very low or undetectable throughout the
      ovulatory process in extracts prepared from the granulosa cell layer. In
      contrast, a significant increase in P-selectin transcript was observed between 30
      and 39 h post-hCG in extracts obtained from thecal layers (P < 0.05). Likewise,
      immunohistochemistry revealed an increase of immunoreactive P-selectin protein in
      the vascular endothelium present in thecal layers of follicles isolated 36 and 39
      h post-hCG. Thus, the present study describes, to our knowledge for the first
      time, the primary structure of equine P-selectin and the regulation of P-selectin
      transcript and protein in follicular thecal endothelial cells before ovulation.

PMID- 15564600
TI  - Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of
      preovulatory follicle cells in rat ovary.
AB  - Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have
      been widely used to inhibit gonadotropin pituitary release. Aside from the effect
      of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has
      extrapituitary effects, particularly on rat and human ovaries. In the present
      study, we evaluated the direct in vivo effects of the GnRH-a, leuprolide acetate
      (LA), or the GnRH-ant, Antide (Ant), either singly or together, on ovarian
      follicular development in prepubertal eCG-treated rats. LA significantly
      decreased ovarian weight, whereas Ant increased ovarian weight compared with
      controls; however, coinjection of both compounds had no effect. In addition, LA
      increased the number of preantral follicles (PFs) and atretic follicles, and
      decreased the number of early antral follicles (EAFs) and preovulatory follicles
      (POFs). Coinjection of Ant interfered with this LA effect. Ant alone increased
      the number of POFs compared with that of controls. Analysis of apoptosis has
      shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs;
      however, Ant prevented this effect. In addition, Ant alone decreased the
      percentage of apoptotic cells in EAFs and POFs. Data have shown that Ant per se
      inhibited BAX translocation from cytosol to mitochondria and retained cytochrome
      C in the mitochondria, whereas LA induced cytochrome C release. We conclude that
      Ant inhibits apoptosis in preovulatory follicles through a decrease of BAX
      translocation to mitochondria, suggesting that GnRH may act as a physiological
      intraovarian modulator factor that is able to interfere with follicular
      development through an increase in apoptotic events mediated by an imbalance
      among the BCL-2 family members.

PMID- 15564601
TI  - Expression of the putative sterol binding protein Stard6 gene is male germ cell
      specific.
AB  - Mammalian spermatogenesis is orchestrated by many specific molecular and cellular
      events. To understand the detailed mechanism by which spermatogenesis is
      controlled, the specific genes involved in this process must be identified and
      studied. From the subtracted cDNA library of rat testis prepared using the
      representational difference analysis (RDA) method, we isolated the cDNA clone of
      steroidogenic acute regulatory (StAR) protein-related lipid transfer (START)
      protein 6 (Stard6). Stard6 cDNA consists of 1146 base pairs of nucleotides and
      has the longest open reading frame, of 227 amino acids. Northern blot analysis
      revealed Stard6 mRNA to be testis-specific. The mRNA transcript appeared from the
      third week of postnatal development, and the expression level increased up to
      adulthood. Moreover, in situ hybridization showed Stard6 mRNA expression to be
      germ cell-specific and expressed only during the maturation stages of round and
      elongated spermatids of adult rat testis. Western blot analysis with Stard6
      antibody revealed a 28-kDa Stard6 protein only in testis. Immunohistochemistry
      further confirmed localization of Stard6 protein expressed in mature germ cells,
      in concert with the in situ hybridization result. Taken together, these results
      suggest that Stard6, a member of the START protein family, may play a role during
      germ cell maturation in adult rat testis.

PMID- 15564602
TI  - Differential effects of phthalates on the testis and the liver.
AB  - Phthalates have been shown to elicit contrasting effects on the testis and the
      liver, causing testicular degeneration and promoting abnormal hepatocyte
      proliferation and carcinogenesis. In the present study, we compared the effects
      of phthalates on testicular and liver cells to better understand the mechanisms
      by which phthalates cause testicular degeneration. In vivo treatment of rats with
      di-(2-ethylhexyl) phthalate (DEHP) caused a threefold increase of germ cell
      apoptosis in the testis, whereas apoptosis was not changed significantly in
      livers from the same animals. Western blot analyses revealed that peroxisome
      proliferator-activated receptor (PPAR) alpha is equally abundant in the liver and
      the testis, whereas PPAR gamma and retinoic acid receptor (RAR) alpha are
      expressed more in the testis. To determine whether the principal metabolite of
      DEHP, mono-(2-ethylhexyl) phthalate (MEHP), or a strong peroxisome proliferator,
      4-chloro-6(2,3-xylindino)-2-pyrimidinylthioacetic acid (Wy-14,643), have a
      differential effect in Sertoli and liver cells by altering the function of RAR
      alpha and PPARs, their nuclear trafficking patterns were compared in Sertoli and
      liver cells after treatment. Both MEHP and Wy-14,643 increased the nuclear
      localization of PPAR alpha and PPAR gamma in Sertoli cells, but they decreased
      the nuclear localization of RAR alpha, as previously shown. Both PPAR alpha and
      PPAR gamma were in the nucleus and cytoplasm of liver cells, but RAR alpha was
      predominant in the cytoplasm, regardless of the treatment. At the molecular
      level, MEHP and Wy-14,643 reduced the amount of phosphorylated mitogen-activated
      protein kinase (activated MAPK) in Sertoli cells. In comparison, both MEHP and Wy
      14,643 increased phosphorylated MAPK in liver cells. These results suggest that
      phthalates may cause contrasting effects on the testis and the liver by
      differential activation of the MAPK pathway, RAR alpha, PPAR alpha, and PPAR
      gamma in these organs.

PMID- 15564603
TI  - Variation in macrophage-migration-inhibitory-factor immunoreactivity during
      porcine gestation.
AB  - The localization and activity of macrophage migration inhibitory factor (MIF) was
      investigated in the interhemal region of the noninvasive, diffuse, folded
      epitheliochorial placenta and in the nonpregnant uterus of the pig. MIF, a
      proinflammatory cytokine with many actions on macrophages and monocytes, may play
      an important role in materno-fetal immuno-tolerance during placental
      establishment, modulation, and growth. Immunohistochemical staining with anti
      human MIF polyclonal antibodies was carried out on placental sections from 11
      stages of gestation (16-95 days postcoitus) and on nonpregnant uterus at 13 days
      postestrus. Western blot analysis confirmed the specificity of the anti-human MIF
      polyclonal antibodies on pig tissues. MIF staining was intense in both the
      trophoblast and maternal epithelium in the early stages; in the later stages, it
      decreased dramatically in the maternal epithelium but remained high in the
      trophoblast. The uterine glands showed immunoreactivity at all stages, and the
      maternal and fetal epithelial linings of the areolar cavity showed high
      reactivity at Day 25. The vasculature also showed staining for MIF, and an
      intense to moderate staining was shown in the nonpregnant uterus, mostly in the
      surface and glandular epithelium. The high activity of MIF in the maternal and
      fetal tissues throughout placentation and its expression in the nonpregnant
      uterus indicate a regulatory role for MIF during embryo receptivity and
      epitheliochorial placentation.

PMID- 15564605
TI  - Brazil: growers' lobby stalls FCTC.

PMID- 15564606
TI  - Japan, India: mobile smoking vans.

PMID- 15564607
TI  - European Union: shock at Rylander appointment.

PMID- 15564608
TI  - New Zealand: hospitality trade's "mindset" problem.

PMID- 15564609
TI  - Uganda: official's "shock" over warning size.

PMID- 15564610
TI  - UK: how did these get here?

PMID- 15564614
TI  - Tobacco smoking using a waterpipe: a re-emerging strain in a global epidemic.
AB  - CONTEXT: The global tobacco epidemic may kill 10 million people annually in the
      next 20-30 years, with 70% of these deaths occurring in developing countries.
      Current research, treatment, and policy efforts focus on cigarettes, while many
      people in developing regions (Asia, Indian subcontinent, Eastern Mediterranean)
      smoke tobacco using waterpipes. Waterpipes are increasing in popularity, and more
      must be learned about them so that we can understand their effects on public
      health, curtail their spread, and help their users quit. OBJECTIVE: To conduct a
      comprehensive review regarding global waterpipe use, in order to identify current
      knowledge, guide scientific research, and promote public policy. DATA SOURCES: A
      Medline search using as keywords "waterpipe", "narghile", "arghile", "shisha",
      "hookah", "goza", "hubble bubble" and variant spellings (for example, "hooka";
      "hukka") was conducted. Resources compiled recently by members of GLOBALink were
      used. STUDY SELECTION: Every identified published study related to waterpipe use
      was included. DATA SYNTHESIS: Research regarding waterpipe epidemiology and
      health effects is limited; no published studies address treatment efforts.
      Waterpipe use is increasing globally, particularly in the Eastern Mediterranean
      Region, where perceptions regarding health effects and traditional values may
      facilitate use among women and children. Waterpipe smoke contains harmful
      constituents and there is preliminary evidence linking waterpipe smoking to a
      variety of life threatening conditions, including pulmonary disease, coronary
      heart disease, and pregnancy related complications. CONCLUSIONS: More scientific
      documentation and careful analysis is required before the spread of waterpipe use
      and its health effects can be understood, and empirically guided treatment and
      public policy strategies can be implemented.

PMID- 15564615
TI  - Relation between access to tobacco and adolescent smoking.
AB  - OBJECTIVE: To examine the relation between rates of sales of tobacco to minors
      and youth smoking prevalence. DESIGN: Repeated annual cross sectional surveys.
      SETTING: Seventy five communities in Oregon. PARTICIPANTS: A random sample of
      students in grades 8 and 11 (ages 13 and 17 years) and retail outlets in each
      participating community. MAIN OUTCOME MEASURES: Thirty day and daily smoking
      prevalence. RESULTS: The rate of illegal merchant sales in the communities was
      related to the smoking rate for 11th graders in those communities, but not for
      8th graders. For every 10% increase in illegal sales rates there was an estimated
      0.8% increase in 11th grade 30 day smoking prevalence and a 0.4% increase in
      daily smoking. Communities with lower illegal merchant sales rates had expanded
      use of social sources and reduced use of commercial sources by 11th graders, with
      the opposite pattern seen in 8th graders. CONCLUSIONS: There appears to be a
      relatively small positive linear relation between the community rate of sales to
      minors and 11th grade youth smoking prevalence in those communities. Youth adjust
      their tobacco sources depending on the level of commercial availability.

PMID- 15564616
TI  - An international analysis of cigarette affordability.
AB  - OBJECTIVE: To investigate how affordable cigarettes are in developed and
      developing countries, and to calculate by how much the affordability of
      cigarettes has changed between 1990 and 2001; and secondly, to investigate the
      relation between cigarette affordability and consumption. DESIGN: Affordability
      was defined as the cost of cigarettes relative to per capita income. Trends in
      cigarette affordability, and affordability elasticities of demand, were estimated
      using regression techniques. SUBJECTS: Seventy countries were investigated, of
      which 28 are categorised as high income developed countries, while 42 are
      categorised as developing countries. Cigarette prices were obtained for the main
      city/cities in the countries. RESULTS: Despite the fact that cigarettes are more
      expensive in developed countries, the high levels of income make cigarettes more
      affordable in these countries vis-a-vis developing countries. Of the 28 developed
      countries, cigarettes became more affordable in 11 and less affordable in 17
      countries during the 1990s. Of the 42 developing countries, cigarettes became
      more affordable in 24 and less affordable in 18 countries. Based on a cross
      sectional analysis, a 1% increase in the relative income price (the inverse of
      cigarette affordability) is expected to decrease cigarette consumption by between
      0.49-0.57%. CONCLUSIONS: Cigarette affordability, more than just the price,
      determines cigarette consumption. While cigarettes have become more affordable in
      many developing countries, some developing countries (for example, South Africa,
      Poland, and Thailand) have implemented strong and effective tobacco control
      policies, and have been able to decrease cigarette consumption as a result.

PMID- 15564617
TI  - Relation between local restaurant smoking regulations and attitudes towards the
      prevalence and social acceptability of smoking: a study of youths and adults who
      eat out predominantly at restaurants in their town.
AB  - OBJECTIVE: To examine the relation between strength of local restaurant smoking
      regulations and smoking related social norms among youths and adults. DESIGN: We
      used generalised estimating equations logistic regression analysis to examine the
      relation between regulation strength and youths' and adults' perceptions of adult
      smoking prevalence and the social acceptability of smoking in their town, while
      controlling for baseline anti-smoking sentiment in the town. SETTING: Each of the
      351 Massachusetts towns were classified as having strong (complete smoking ban),
      medium (restriction of smoking to enclosed, separately ventilated areas), or weak
      (all others) restaurant smoking regulations. SUBJECTS: 1147 Massachusetts youths
      ages 12-17 years and 2116 adults who reported that they often or always eat out
      in their own town, drawn from a random digit dial survey. MAIN OUTCOME MEASURES:
      Perceived adult smoking prevalence and perceived social acceptability of smoking
      in restaurants, in bars, or in general. RESULTS: Compared to youths from towns
      with weak regulations, youths from towns with strong regulations were more likely
      to perceive lower adult smoking prevalence (odds ratio (OR) 1.71; 95% confidence
      interval (CI) 1.02 to 2.84) and social unacceptability of adult smoking (OR 2.00,
      95% CI 1.29 to 3.08) in their town. Adults from towns with strong regulations
      were not more likely to perceive lower adult smoking prevalence, but had more
      than twice the odds of perceiving that smoking was unacceptable in restaurants
      (OR 2.19, 95% CI 1.58 to 3.02) or bars (OR 2.51, 95% CI 1.90 to 3.31).
      CONCLUSIONS: Strong local restaurant smoking regulations are associated with
      favourable smoking related social norms among youths and adults.

PMID- 15564618
TI  - Impacts of the Master Settlement Agreement on the tobacco industry.
AB  - OBJECTIVE: To assess effects of the Master Settlement Agreement (MSA) and the
      four individual state settlements on tobacco company decisions and performance.
      DESIGN: 10-K reports filed with the US Securities and Exchange Commission, firm
      and daily data from the Center for Research in Security Prices, stock price
      indices, market share and advertising data, cigarette export and domestic
      consumption data, and newspaper articles were used to assess changes before (1990
      98) and after (1999-2002) the MSA was implemented. SUBJECTS: Five major tobacco
      manufacturers in the USA. MAIN OUTCOME MEASURES: Stockholder returns, operating
      performance of defendant companies, exports, market share of the original
      participants in the MSA, and advertising/promotion expenditures. RESULTS: Returns
      to investments in the tobacco industry exceeded returns from investments in
      securities of other companies, using each of four indexes as comparators.
      Domestic tobacco revenues increased during 1999-2002 from pre-MSA levels. Profits
      from domestic sales rose from levels prevailing immediately before the MSA. There
      is no indication that the MSA caused an increase in tobacco exports. Total market
      share of the original participating manufacturers in the MSA decreased. Total
      advertising expenditures by the tobacco companies increased at a higher rate than
      the 1990-98 trend during 1999-2002, but total advertising expenditures net of
      spending on coupons and promotions decreased. CONCLUSION: The experience during
      the post-MSA period demonstrates that the MSA did no major harm to the companies.
      Some features of the MSA appear to have increased company value and
      profitability.

PMID- 15564619
TI  - A nicotine delivery device without the nicotine? Tobacco industry development of
      low nicotine cigarettes.
AB  - BACKGROUND: Defining harm reduction and regulating potentially reduced exposure
      products (PREPs), including low nicotine products, are key issues in tobacco
      control policy. The US Congress has been considering legislation authorising the
      Food and Drug Administration (FDA) to regulate tobacco products. OBJECTIVE: To
      investigate tobacco industry perceptions, interests, motivations, and knowledge
      regarding the marketability of low nicotine tobacco products. METHODS:
      Qualitative analysis of internal tobacco industry documents identified in the
      Legacy Tobacco Documents Library between February 2002 and June 2004. Search
      terms included low-, no-, reduced-nicotine; denicotinization; low-, reduced-
      alkaloids; Next; de-nic; and key names of people, organisations, projects, and
      their common abbreviations and acronyms. RESULTS: The tobacco industry has made
      repeated efforts to develop low nicotine cigarettes. Reasons for doing so include
      consumer appeal and economic importance in a highly competitive cigarette market
      for "healthier" products. The industry considered the development of a new
      "denic" market segment a critical challenge. CONCLUSIONS: The tobacco industry
      exploits consumer misunderstanding of the health effects of nicotine in
      development and marketing efforts. The industry has risked the development of a
      less addictive product to expand the market reach of tobacco products based on
      perceived health benefits and appeal to quitters.

PMID- 15564620
TI  - The wealth effects of smoking.
AB  - OBJECTIVE: To investigate the impact of smoking on the wealth of US young baby
      boomers. METHODOLOGY: The research analyses self reported responses of both
      smoking habits and wealth holdings from a nationally representative sample of US
      individuals born between 1957 to 1964 (n = 8908). Data are from four waves (1984,
      1992, 1994, 1998) of the National Longitudinal Survey of Youth 1979 cohort, a
      random survey of individuals conducted by the US Department of Labor using a
      stratified multistage area sample design. RESULTS: Regression results show lower
      net worth is associated with smoking, after holding constant a variety of
      demographic factors. Respondents who were ever heavy smokers are associated with
      a reduction in net worth of over 8300 dollars while light smokers are 2000
      dollars poorer compared to non-smokers. Beyond this reduction, each adult year of
      smoking is associated with a decrease in net worth of 410 dollars or almost 4%.
      CONCLUSIONS: While a causal relation cannot be proven, smokers appear to pay for
      tobacco expenditures out of income that is saved by non-smokers. Hence,
      reductions in smoking will boost wealth, especially among the poor.

PMID- 15564621
TI  - The Living Tomorrow Project: how Philip Morris has used a Belgian tourist
      attraction to promote ventilation approaches to the control of second hand smoke.
AB  - STUDY OBJECTIVE: To examine the involvement of Philip Morris in Living Tomorrow 2
      and determine the rationale behind its involvement. DESIGN: Research was
      conducted through a web based search of internal tobacco industry documents made
      publicly available through litigation. MAIN RESULTS: For approximately 1,000,000
      euros Philip Morris (now Altria) became a co-initiator of Living Tomorrow 2, a
      tourist complex in Belgium that aims to demonstrate how we will be living in the
      future. In addition to promoting the company and its grocery products, Philip
      Morris is using the complex and its website to promote ventilation as a means of
      accommodating smokers and non-smokers in the indoor environment. Particular
      emphasis was placed on the bar and restaurant areas. Despite the rationale for
      its involvement, Philip Morris fails to acknowledge its role as a cigarette
      manufacturer. As a form of corporate sponsorship Philip Morris thought its
      involvement could evade any European tobacco advertising ban. CONCLUSIONS: Philip
      Morris is using a tourist attraction to promote its views on control of second
      hand smoke (SHS) and accommodation of smokers and non-smokers in the indoor
      environment. However, ventilation does not deal with the health effects of SHS.
      Policymakers must be cognisant of the devious tactics the industry employs to
      promote its own agenda, especially in relation to indoor air quality and smoking
      in public places. Tobacco control legislation should be continually modified and
      strengthened in response to the changing activities of the tobacco industry as it
      strives to evade existing legislation and deter the advent of new legislation.

PMID- 15564622
TI  - How Philip Morris unlocked the Japanese cigarette market: lessons for global
      tobacco control.
AB  - BACKGROUND: The Framework Convention on Tobacco Control includes tobacco
      advertising restrictions that are strongly opposed by the tobacco industry.
      Marketing strategies used by transnational tobacco companies to open the Japanese
      market in the absence of such restrictions are described. METHODS: Analysis of
      internal company documents. FINDINGS: Between 1982 and 1987 transnational tobacco
      companies influenced the Japanese government through the US Trade Representative
      to open distribution networks and eliminate advertising restrictions. US
      cigarette exports to Japan increased 10-fold between 1985 and 1996. Television
      advertising was central to opening the market by projecting a popular image
      (despite a small actual market share) to attract existing smokers, combined with
      hero-centred advertisements to attract new smokers. Philip Morris's campaigns
      featured Hollywood movie personalities popular with young men, including James
      Coburn, Pierce Brosnan, Roger Moore, and Charlie Sheen. Event sponsorships
      allowed television access despite restrictions. When reinstatement of television
      restrictions was threatened in the late 1980s, Philip Morris more than doubled
      its television advertising budget and increased sponsorship of televised events.
      By adopting voluntary advertising standards, transnational companies delayed a
      television advertising ban for over a decade. CONCLUSIONS: Television image
      advertising was important to establish a market, and it has been enhanced using
      Hollywood personalities. Television advertising bans are essential measures to
      prevent industry penetration of new markets, and are less effective without
      concurrent limits on sponsorship and promotion. Comprehensive advertising
      restrictions, as included in the Framework Convention for Tobacco Control, are
      vital for countries where transnational tobacco companies have yet to penetrate
      the market.

PMID- 15564623
TI  - Regional, disease specific patterns of smoking-attributable mortality in 2000.
AB  - BACKGROUND: Smoking has been causally associated with increased mortality from
      several diseases, and has increased considerably in many developing countries in
      the past few decades. Mortality attributable to smoking in the year 2000 was
      estimated for adult males and females, including estimates by age and for
      specific diseases in 14 epidemiological subregions of the world. METHODS: Lung
      cancer mortality was used as an indirect marker of the accumulated hazard of
      smoking. Never-smoker lung cancer mortality was estimated based on the household
      use of coal with poor ventilation. Estimates of mortality caused by smoking were
      made for lung cancer, upper aerodigestive cancer, all other cancers, chronic
      obstructive pulmonary disease (COPD), other respiratory diseases, cardiovascular
      diseases, and selected other medical causes. Estimates were limited to ages 30
      years and above. RESULTS: In 2000, an estimated 4.83 million premature deaths in
      the world were attributable to smoking, 2.41 million in developing countries and
      2.43 million in industrialised countries. There were 3.84 million male deaths and
      1.00 million female deaths attributable to smoking. 2.69 million smoking
      attributable deaths were between the ages of 30-69 years, and 2.14 million were
      70 years of age and above. The leading causes of death from smoking in
      industrialised regions were cardiovascular diseases (1.02 million deaths), lung
      cancer (0.52 million deaths), and COPD (0.31 million deaths), and in the
      developing world cardiovascular diseases (0.67 million deaths), COPD (0.65
      million deaths), and lung cancer (0.33 million deaths). The share of male and
      female deaths and younger and older adult deaths, and of various diseases in
      total smoking attributable deaths exhibited large inter-regional heterogeneity,
      especially in the developing world. CONCLUSIONS: Smoking was an important cause
      of global mortality in 2000, affecting a large number of diseases. Age, sex, and
      disease patterns of smoking-caused mortality varied greatly across regions, due
      to both historical and current smoking patterns, and the presence of other risk
      factors that affect background mortality from specific diseases.

PMID- 15564624
TI  - Tobacco attributable deaths in South Africa.
AB  - BACKGROUND: In mid 1998, a question "Was the deceased a smoker five years ago?"
      was introduced on the newly revised South African death notification form.
      DESIGN: A total of 16,230 new death notification forms from 1998 have been coded,
      and comparison of the prevalence of smoking among those who died of different
      causes was used to estimate, by case-control comparisons, tobacco attributed
      mortality in South Africa. Cases comprised deaths from causes known (from other
      studies) to be causally associated with smoking, and controls comprised deaths
      from medical conditions expected to be unrelated to smoking. Those who died from
      external causes, and from diseases strongly related to alcohol consumption, were
      excluded. SUBJECTS: Reports were available from 5340 deceased adults (age 25+),
      whose smoking status was given by a family member. RESULTS: Significantly
      increased risks were found for deaths from tuberculosis (odds ratio (OR) 1.61,
      95% confidence interval (CI) 1.23 to 2.11), chronic obstructive pulmonary disease
      (COPD) (OR 2.5, 95% CI 1.9 to 3.4), lung cancer (OR 4.8, 95% CI 2.9 to 8.0),
      other upper aerodigestive cancer (OR 3.0, 95% CI 1.9 to 4.9) and ischaemic heart
      disease (OR 1.7, 95% CI 1.2 to 2.3). CONCLUSION: If smokers had the same death
      rate as non-smokers, 58% of lung cancer deaths, 37% of COPD deaths, 20% of
      tuberculosis deaths, and 23% of vascular deaths would have been avoided. About 8%
      of all adult deaths in South Africa (more than 20 000 deaths a year) were caused
      by smoking.

PMID- 15564625
TI  - Tobacco use in popular movies during the past decade.
AB  - OBJECTIVE: The top 50 commercially successful films released per year from 1991
      to 2000 were content coded to assess trends in tobacco use over time and
      attributes of films predictive of higher smoking rates. DESIGN: This
      observational study used media content analysis methods to generate data about
      tobacco use depictions in films studied (n = 497). Films are the basic unit of
      analysis. Once films were coded and preliminary analysis completed, outcome data
      were transformed to approximate multivariate normality before being analysed with
      general linear models and longitudinal mixed method regression methods. MAIN
      OUTCOME MEASURES: Tobacco use per minute of film was the main outcome measure
      used. Predictor variables include attributes of films and actors. Tobacco use was
      defined as any cigarette, cigar, and chewing tobacco use as well as the display
      of smoke and cigarette paraphernalia such as ashtrays, brand names, or logos
      within frames of films reviewed. RESULTS: Smoking rates in the top films
      fluctuated yearly over the decade with an overall modest downward trend (p <
      0.005), with the exception of R rated films where rates went up. CONCLUSIONS: The
      decrease in smoking rates found in films in the past decade is modest given
      extensive efforts to educate the entertainment industry on this issue over the
      past decade. Monitoring, education, advocacy, and policy change to bring tobacco
      depiction rates down further should continue.

PMID- 15564626
TI  - Adults only: the prevalence of tobacco promotions in bars and clubs in the Boston
      area.
AB  - OBJECTIVE: To document the nature and prevalence of tobacco promotions in bars
      and clubs in a major US city. DESIGN: We conducted systematic observations in a
      representative sample of 38 establishments in the Boston area, half of which had
      been advertised in a tobacco company ad. We also observed seven events in six
      additional clubs hosting Camel Casbah promotions. Telephone interviews were later
      completed with club managers. MAIN OUTCOME MEASURE: Use of branded give-away
      items, distribution of free cigarette samples, managers' reports of costs and
      benefits of hosting promotions. RESULTS: The majority of the 38 clubs were
      observed to use bar paraphernalia including matchbooks with tobacco brand logos,
      regardless of their history of appearing in tobacco sponsored ads. Free cigarette
      samples were not observed at any of the sampled clubs, but were a feature of
      every Casbah event. Managers of clubs in the advertised group were somewhat more
      likely to report having hosted promotions, but 44% of managers of non-advertised
      clubs indicated that tobacco promotions had occurred in their establishments in
      the past. Approximately one third of club managers viewed public links with a
      tobacco company as a negative feature of hosting promotions. CONCLUSIONS: Based
      on managers' reports, tobacco promotions occurred in more than 50% of the Boston
      area entertainment venues frequented by young adults. Cigarette companies should
      be required to inform the attorney general of plans to conduct promotions in
      adult-only venues to facilitate monitoring of compliance with the Master
      Settlement Agreement. The negative health and business consequences of hosting
      promotions should be communicated to bar owners.

PMID- 15564627
TI  - Is household smoking status associated with expenditure on food at restaurants,
      alcohol, gambling and insurance? Results from the 1998-99 Household Expenditure
      Survey, Australia.
AB  - AIM: To examine how household expenditure on food at restaurants, alcohol,
      gambling and insurance vary between smoking and non-smoking households. DESIGN:
      Cross sectional survey of households from private dwellings, conducted by the
      Australian Bureau of Statistics (ABS), using a stratified multistage area sample
      design. SETTING: Australia, 1998-99. PARTICIPANTS: Nationally representative
      sample of households (n = 6892). MAIN OUTCOME MEASURES: Expenditure on meals at
      restaurants, alcohol, alcoholic beverages at licensed premises, gambling, and
      insurance. RESULTS: The odds of reporting expenditure on restaurant food and
      health insurance were 20% and 40% smaller for smoking than non-smoking
      households, respectively. The odds of reporting expenditure on alcohol (not
      including expenditure at licensed premises), drinking at licensed premises, and
      gambling were 100%, 50%, and 40% greater for smoking than for non-smoking
      households, respectively. CONCLUSIONS: The study suggests that smokers are more
      likely to engage in risky behaviour. Implementing smoking bans in licensed
      premises and gambling venues can provide an opportunity to reduce smoking
      prevalence. Quitting or cutting down smoking can provide opportunities for
      expenditure on other products or services, and enhance standards of living.

PMID- 15564628
TI  - Which smokers use the smoking cessation Quitline in Hong Kong, and how effective
      is the Quitline?
AB  - OBJECTIVE: To describe the characteristics of the Chinese subjects who utilised
      the first telephone smoking cessation service in Hong Kong, and to evaluate its
      effectiveness. METHODS: The Quitline provided Hong Kong residents with free
      telephone smoking cessation services which was publicised through a press
      conference, media reports, pamphlets, and posters at public and private hospitals
      and clinics. Callers who completed an initial interview from 13 December 2000 to
      31 May 2002 were included. Smokers were interviewed using a structured record
      sheet and provided with stage matched counselling. A follow up interview was
      carried out after six months. Analysis was conducted by intention-to-treat.
      RESULTS: Of the 1120 callers who completed initial assessments, 1047 were current
      smokers and 872 consented to follow ups. Compared to the general smoking
      population, the Quitline attracted more of those who were female, younger,
      single, unemployed, higher educated, smoking more than 20 cigarettes per day, and
      those with quitting experience. At six months, 12% (95% confidence interval 10%
      to 15%) of the participants reported that they had not smoked a cigarette for the
      past seven days. A stepwise logistic regression model showed that the use of
      nicotine replacement therapy at the present attempt to quit, having made one or
      more serious attempts to quit in the past, perceiving less difficulties in
      quitting, and smoking the first cigarette at age 15 years or above were
      significant predictors of quitting. CONCLUSION: This first Quitline in Asia
      appears to be acceptable to Chinese smokers, with quit rate comparable to those
      of better funded Quitlines in the West. A low cost Quitline is a promising model
      for smoking cessation services in the East.

PMID- 15564629
TI  - Genetically decreased CYP2A6 and the risk of tobacco dependence: a prospective
      study of novice smokers.
AB  - OBJECTIVE: Case control studies in adults suggest that defective alleles in the
      gene that codes for the hepatic cytochrome P450 2A6 (CYP2A6) protect against
      nicotine dependence (ND) and higher levels of cigarette consumption. These two
      hypotheses were tested in young adolescents. DESIGN: Self reports of tobacco use
      and ND symptoms were collected every 3-4 months in a prospective study of 1293
      grade 7 students from a convenience sample of 10 schools. SUBJECTS: 281 smokers
      with genetic data were analysed; those who were not already tobacco dependent and
      who had inhaled (n = 228) were followed 29.9 months on average, until they became
      dependent or were censored. MAIN OUTCOME MEASURES: The association between
      metabolic activity, represented by CYP2A6 genotype, and conversion to dependence
      was analysed using Cox's proportional hazards model. RESULTS: During follow up 67
      subjects (29.4%) became dependent. Relative to CYP2A6*1/*1, having 1-2 copies of
      the inactive CYP2A6*2 or *4 variant was a strong risk factor for developing
      dependence (hazard ratio 2.8, 95% confidence 1.3 to 6.3). Subjects with 1-2
      partially inactive CYP2A6*9 or *12 variants were not at increased risk. Mean past
      week cigarette consumption at the end of follow up (controlling for age, sex, and
      number of months since first inhalation) among dependent subjects was 29.1 among
      normal inactivators, compared to 17.2, and 12.7 among slower (1-2 copies of *9 or
      *12), and slowest (1-2 copies of *2 or *4) inactivators, respectively (p = 0.09).
      CONCLUSION: Adolescents with 1-2 copies of CYP2A6*2 or *4 are at substantially
      increased risk of becoming dependent but smoke less once dependent. Genetic risk
      for ND may need to be considered in the conceptualisation of tobacco control
      programmes for adolescents.

PMID- 15564630
TI  - Merchandising of cigarettes in San Francisco pharmacies: 27 years later.
AB  - OBJECTIVE: To estimate changes since 1976 in the proportion of San Francisco
      pharmacies that sell cigarettes and to characterise the advertising of cigarettes
      and the merchandising of non-prescription nicotine replacement therapy (NRT)
      products in these retail establishments. METHODS AND SETTING: 100 randomly
      selected San Francisco pharmacies were visited in 2003. Pharmacies were
      characterised based on the sale of cigarettes, advertising for cigarettes, and
      the merchandising of non-prescription NRT products. RESULTS: In 2003, 61% of
      pharmacies sold cigarettes, a significant decrease compared to 89% of pharmacies
      selling cigarettes in 1976 (p < 0.001); 84% of pharmacies selling cigarettes also
      displayed cigarette advertising. Non-prescription NRT products were stocked by
      78% of pharmacies, and in 55% of pharmacies selling cigarettes, the NRT products
      were stocked immediately adjacent to the cigarettes. CONCLUSIONS: Since 1976,
      there has been a decline in the overall proportion of pharmacies in San Francisco
      that sell cigarettes yet most pharmacies, particularly traditional chain
      pharmacies, continue to merchandise the primary known risk factor for death in
      the USA.

PMID- 15564631
TI  - Achieving the Framework Convention on Tobacco Control's potential by investing in
      national capacity.
AB  - May 2003 marked a critical achievement in efforts to stem the global tobacco
      epidemic, as the member states of the World Health Organization unanimously
      endorsed the Framework Convention on Tobacco Control (FCTC). However, the
      adoption of the FCTC signifies only the end of the beginning of effective global
      action to control tobacco. Over the next several years the utility of the FCTC
      process and the treaty itself will be tested as individual countries seek to
      ratify and implement the treaty's obligations. Significant barriers to the
      treaty's long term success exist in many countries. It is crucial that the
      international tobacco control community now refocuses its efforts on national
      capacity building and ensures that individual countries have the knowledge,
      tools, data, people, and organisations needed to implement the convention and
      develop sustained tobacco control programmes. This paper provides a model of
      national tobacco control capacity and offers a prioritised agenda for action.

PMID- 15564632
TI  - Food and Drug Administration regulation of tobacco products: introduction.

PMID- 15564633
TI  - Food and Drug Administration regulation of tobacco: snatching defeat from the
      jaws of victory.

PMID- 15564634
TI  - Opposition in search of a rationale: the case for Food and Drug Administration
      regulation.

PMID- 15564635
TI  - Advocacy in action: extreme corporate makeover interruptus: denormalising tobacco
      industry corporate schmoozing.
AB  - The tobacco industry continues to seek corporate "respectability", despite being
      responsible for the deaths of millions of smokers worldwide every year.

PMID- 15564636
TI  - Corporate social responsibility and the tobacco industry: hope or hype?
AB  - Corporate social responsibility (CSR) emerged from a realisation among
      transnational corporations of the need to account for and redress their adverse
      impact on society: specifically, on human rights, labour practices, and the
      environment. Two transnational tobacco companies have recently adopted CSR:
      Philip Morris, and British American Tobacco. This report explains the origins and
      theory behind CSR; examines internal company documents from Philip Morris showing
      the company's deliberations on the matter, and the company's perspective on its
      own behaviour; and reflects on whether marketing tobacco is antithetical to
      social responsibility.

PMID- 15564637
TI  - The economic impact of smoke-free legislation on sales turnover in restaurants
      and pubs in Tasmania.

PMID- 15564638
TI  - Accelerated nodulosis during methotrexate therapy in a patient with systemic
      lupus erythematosus and Jaccoud's arthropathy.

PMID- 15564639
TI  - Delayed multiple injection site reaction in a rheumatoid arthritis patient
      treated with etanercept.

PMID- 15564640
TI  - Is syndrome of inappropriate antidiuretic hormone secretion an extra-articular
      manifestation of rheumatoid arthritis?

PMID- 15564641
TI  - Reversible focal myositis in a patient taking venlafaxine.

PMID- 15564643
TI  - Inaccurate acupuncture history.

PMID- 15564644
TI  - Assessing patient, carer and healthcare professional education provided by the
      Birmingham Arthritis Resource Centre (BARC).

PMID- 15564646
TI  - Re: Goodacre and Goodacre. Factors influencing the beliefs of patients with
      rheumatoid arthritis regarding disease-modifying medication.

PMID- 15564649
TI  - Trace element concentrations and superoxide dismutase and catalase activities in
      benign and malignant larynx tumors.
AB  - The plasma and erythrocyte levels of zinc, copper, and magnesium and the
      activities of red-cell copper-zinc superoxide dismutase (Cu/Zn-SOD) and catalase
      (CAT) were determined in patients with benign and malignant tumors of the larynx.
      Blood samples from patients and healthy controls were drawn using heparinized
      tubes. The erythrocyte Cu/Zn-SOD and CAT activities were determined
      spectrophotometrically and the zinc, copper, and magnesium concentrations were
      determined in erythrocyte and plasma by atomic absorption spectrometry. Variance
      analysis was employed in the statistical evaluation of the findings. There was a
      significant increase in red-cell Cu/Zn-SOD activity in the subjects with
      malignant and benign tumors compared to controls (p<0.001). The CAT activity
      increased only in the benign tumor group (p<0.01). The plasma zinc concentrations
      were significantly lower in the malignant tumor group (p<0.05) and significantly
      higher in the benign tumor group (p<0.01). The erythrocyte copper concentrations
      were significantly lower in both benign and malignant tumor groups (p<0.001). The
      plasma copper and magnesium and the erythrocyte magnesium concentrations did not
      show significant differences relative to controls (p>0.05). The increases in the
      activities of SOD and CAT activities and the changes in trace elements
      concentrations can indicate the presence of increased reactive oxygen species
      that might play a part in the pathogenesis larynx tumors.

PMID- 15564650
TI  - High accumulation of calcium in human uterine artery with aging.
AB  - To elucidate compositional changes of the rami of the internal iliac artery with
      aging, the authors investigated age-related changes of the calcium content in the
      uterine, internal pudendal, umbilical, and obturator arteries by inductively
      coupled plasma-atomic emission spectrometry. After an ordinary dissection was
      finished, the uterine, internal pudendal, umbilical, and obturator arteries were
      resected from 10 female subjects, and the internal pudendal, umbilical, and
      obturator arteries were resected from 10 male subjects. The female subjects
      ranged in age from 52 to 96 yr, and the male subjects ranged in age from 63 to 88
      yr. The calcium content in the uterine artery began to increase in the seventies
      and increased markedly in the nineties. In the internal pudendal artery, the
      calcium content hardly increased up to the eighties and increased significantly
      in the nineties. In contrast, the calcium content did not change in both the
      umbilical and obturator arteries with advancing age. It was found that the
      average content of calcium was the highest in the uterine artery and decreased in
      the order internal pudendal, umbilical, and obturator arteries. The average
      content of calcium in the uterine arteries corresponded to 46-fold the amount of
      the women's obturator arteries, in which it was the lowest. In the cases of men,
      the average content of calcium was higher in the order of the internal pudendal,
      umbilical, and obturator arteries. Regarding the average content of calcium, the
      order internal pudendal, umbilical, and obturator arteries of the men was
      consistent with that of the women.

PMID- 15564651
TI  - Stability and absorption of chromium and absorption of chromium histidinate
      complexes by humans.
AB  - Increased intake of chromium (Cr) often leads to improvements in glucose,
      insulin, lipids, and related variables in studies involving humans and
      experimental and farm animals. However, the results are often variable, depending
      not only on the selection of subjects but also dietary conditions and the form of
      supplemental Cr used. Our objective was to find a Cr supplement suitable for
      humans that was absorbed better than any of those available. Chromium absorption
      by six adult subjects, three males and three females, was determined based on the
      amount of Cr excreted in the urine in the initial 2 d following intake of 200
      microg of Cr of the various forms of chromium tested. The absorption of the newly
      synthesized complexes was greatest for those containing histidine. Urinary Cr
      losses for six control subjects consuming 200 microg of Cr as Cr histidinate
      increased from basal levels of 256+/-48 to 3670+/-338 ng/d compared with 2082+/
      201 ng for Cr picolinate, the currently most popular nutrient supplement, in the
      48 h following Cr consumption. Chromium histidinate complexes were stable and
      absorption was similar to the initial values after more than 2 yr. Mixing of some
      of the complexes with starch, which was postulated to improve Cr absorption, was
      shown to essentially block Cr absorption within 1 mo. These data demonstrate that
      urinary Cr losses need to be determined because stability and absorption of the
      Cr complexes varies widely and could be responsible for the variability in some
      of the Cr supplementation studies. Chromium histidinate complexes are absorbed
      better than any of the Cr complexes currently available and need to be evaluated
      as Cr nutritional supplements.

PMID- 15564652
TI  - Beneficial effects of combined treatment with niacin and chromium on the liver of
      hyperlipemic rats.
AB  - Many studies have shown that niacin and Cr exert combined effects. Significant
      beneficial effects in serum lipid levels following Cr supplementation have been
      reported. Niacin decreases total plasma levels of cholesterol, triglycerides, and
      low-density lipoprotein cholesterol and increases high-density lipoprotein
      cholesterol. In this study, 12-mo-old female Swiss albino rats were used. They
      were randomly divided into four groups. The animals of group I (control) were fed
      with pellet chow. Group II was fed with pellet chow and treated with 250
      microg/kg CrCl3.6H2O and 100 mg/kg niacin for 45 d, by the gavage technique. The
      rats of group III were fed with lipogenic diet consisting of 2% cholesterol, 0.5%
      cholic acid, and 20% sunflower oil added to the pellet chow and given 3%
      alcoholic water for 60 d. Group IV was fed with the same lipogenic diet, and 15 d
      after, the experimental animals were made hyperlipemic; they were treated with
      250 microg/kg CrCl3.6H2O and 100 mg/kg niacin by gavage technique for 45 d. On d
      60, liver and blood samples were taken from the animals. The sections were
      examined under light and electron microscopes. Serum total lipid and cholesterol
      levels were determined by spectrophotometric methods. The aim of the present
      study was to examine whether combined treatment with Cr and niacin have
      beneficial effects on the liver of animals fed with lipogenic diet. In this
      study, beneficial effects of combined treatment with niacin and Cr(III) were
      evaluated. We conclude that a combination of Cr and niacin decrease total
      cholesterol and total lipid levels in serum significantly. In addition, it can be
      said that niacin and Cr can regenerate some of the hepatocytes. This study
      reveals that combined treatment is a better specific drug in hyperlipemia.

PMID- 15564653
TI  - Effect of zinc deficiency and supplementation on lipid peroxidation of renal
      tissue in ovariectomized rats.
AB  - The aim of this study was to investigate how zinc deficiency and supplementation
      affects lipid peroxidation in the renal tissue in ovariectomized rats. Four study
      groups were formed with 10 Spraque-Dawley rats each. Two of the groups served as
      normal and ovariectomized controls; the other two were ovariectomized rats that
      were zinc deficient and zinc supplemented, respectively. The zinc-deficient
      ovariectomized rats showed greater renal and plasma lipid peroxidation, as
      indicated by higher malondialdehyde levels than all other groups (p<0.05). These
      values were higher in the ovariectomized controls than those of the normal
      controls and of the ovariectomized, zinc-supplemented groups (p<0.05), which, in,
      turn, showed no significant differences of their respective renal and plasma
      malondialdehyde values. The renal and erythrocyte glutathione levels in the zinc
      supplemented rats were higher than those in all other groups (p<0.05). The zinc
      deficient group had the lowest renal and erythrocyte glutathione levels (p<0.05).
      The renal tissue zinc levels in the ovariectomized rats were higher than those in
      the zinc-deficient animals, but lower than in the normal controls and zinc
      supplemented rats (p<0.05). The zinc-supplemented animals had the highest renal
      tissue zinc levels (p<0.05). The results of this study suggest that zinc
      deficiency increases renal tissue damage in ovariectomized rats and that zinc
      supplementation can be used to prevent this condition.

PMID- 15564654
TI  - Effects of seasonal and physiological variations on the serum major and trace
      element levels in sheep.
AB  - The aim of this study was to investigate the possible effects of the seasonal and
      physiological variations on the Cu, Zn, Mg, Fe, Se, Ca, K, Na, Cl, and P
      concentrations and their relationships with the estradiol and progesterone levels
      in Sakiz-Ivesi sheep. For this purpose, 34 healthy Sakiz-Ivesi crossbreed sheep
      were divided into two groups. The first group (n=22) was mated and the second
      group (n=12) was not mated. They were raised under pasture conditions and without
      any dietary supplementation. Their serum samples were collected four times a year
      at each season and under each physiologic condition. The periods are 1=early
      pregnancy (October), 2=late pregnancy (January), 3=lactation (April), and 4=dry
      season (July). The results of this study indicated that (1) Mg concentrations in
      serum vary with seasonal variations but not physiological variations, (2) Fe and
      K concentrations in serum vary only with physiological variations, (3) the Cu
      concentration changes not only pregnancy but also through some other hormonal
      changes not caused by pregnancy, (4) Ca, P, and Se concentrations could vary with
      both physiologic and seasonal variations, (5) Zn, Na, and Cl were almost
      identical for both groups and altered depending on neither season of the year nor
      the physiologic status, (6) both increased estradiol level and increased
      progesterone level can raise Cu levels in serum, and (7) increased serum Ca
      concentrations are related with increased estradiol and decreased P and Mg
      levels. These observations suggest that seasonal and physiologic variations and
      sexual cycle have to be taken into consideration for a correct interpretation of
      elements status. If sheep are maintained at pasture conditions, the nutritional
      requirements must be supplemented during certain periods. Otherwise, it is
      apparent that this will cause a decline in the total performance of sheep and,
      consequently, economic lost.

PMID- 15564655
TI  - N-acetylcysteine exposure on lead-induced lipid peroxidative damage and oxidative
      defense system in brain regions of rats.
AB  - Lead (Pb) is known to disrupt the pro-oxidant/antioxidant balance of tissues,
      which leads to biochemical and physiological dysfunction. Oxidative stress is
      considered a possible molecular mechanism involved in Pb neurotoxicity.
      Considering the vulnerability of the brain to oxidative stress under Pb
      neurotoxicity, this study investigated the effects of exposure of the thiol
      antioxidant N-acetylcysteine (NAC) on lead-induced oxidative damage and lipid
      peroxidation in brain regions of the rat. Wister strain rats were exposed to lead
      in the form of lead acetate (20 mg/kg body wt/d) for a period of 2 wk and the
      effects of NAC on lead-induced neurotoxicity in rat brain regions were assessed
      by postadministration of NAC (160 mg/kg body wt/d) for a period of 3 wk. The
      lipid peroxidation byproduct, malondialdehyde (MDA) increased following lead
      exposure in both of the regions, and the antioxidant capacities of the cell in
      terms of the activity of antioxidant enzymes superoxide dismutase (SOD) and
      catalase (CAT) was diminished. Following NAC treatment, lead-induced lipid
      peroxidation decreased and antioxidant enzyme activities improved, with CAT
      showing enhancement in the cerebral region only and SOD showing enhancements in
      the cerebellar region. Our result suggests that thiol-antioxidant supplementation
      following Pb exposure might enhance the reductive status of brain regions by
      arresting the lipid peroxidative damage in brain regions.

PMID- 15564656
TI  - Selecting iodine-enriched vegetables and the residual effect of iodate
      application to soil.
AB  - A greenhouse pot experiment was conducted to select vegetables for iodine uptake.
      The residual effect of iodate fertilization on the growth of and iodine uptake by
      spinach plants were also investigated. Six vegetables, including leafy vegetables
      (pakchoi [Brassica chinensis L.], spinach [Spinacia oleracea L.]), tuber
      vegetables (onion [Allium cepa L.]), shoot vegetables (water spinach [Ipomoea
      aquatica Forsk.], celery [Apium graveolens L.]), and root vegetables (carrot
      [Daucus carota var. sativa DC.]) were examined. Results showed that the
      concentrations of iodate in soil had significant effect on the biomass of edible
      parts of pakchoi and spinach (p<0.01), whereas the concentrations of iodate in
      soil had no significant effect on that of carrots, water spinach, celery, and
      onion. Iodine concentrations in edible parts of vegetables and the transfer
      factors (TFedible parts) of soil-to-edible parts of vegetables significantly
      increased with increasing iodine concentrations in soil (p<0.001), and iodine
      concentrations in edible parts and TFedible parts of spinach were much higher
      than those of other vegetables at any treatment. Both transfer coefficients for
      edible parts (TCedible parts) and for aerial parts (TCaerial parts) of vegetables
      changed differently with increasing iodine concentrations in the soil, and
      TCedible parts and TCaerial parts of spinach were higher than those of other
      vegetables. Therefore, spinach was considered as an efficient vegetable for
      iodine biofortification. Further experiment showed that there is considerable
      residual effect of soil fertilization with iodate.

PMID- 15564657
TI  - Roles of chloroplast RNA polymerase sigma factors in chloroplast development and
      stress response in higher plants.
AB  - Chloroplast transcription in higher plants is performed by two types of RNA
      polymerases, plastid-encoded RNA polymerase (PEP) and nuclear-encoded RNA
      polymerase (NEP). PEP is a eubacteria-type multisubunit enzyme whose catalytic
      core subunits are encoded by the chloroplast genome, whereas NEP is the nuclear
      encoded T7 phage-type single subunit enzyme. PEP is critical for the biogenesis
      and maintenance of chloroplasts, and is finely tuned by the nuclear encoded sigma
      subunits. Of the six Arabidopsis sigma subunits, SIG2 is involved in the
      transcription of several chloroplast tRNA genes, including trnE encoding tRNA
      Glu. SIG2 possibly couples translation and pigment synthesis in chloroplasts. On
      the other hand, SIG5 is induced by various stresses and contributes to repair of
      damaged photosystem II (PSII) through transcription of the psbD and psbC genes.
      Thus target genes and the physiological role of each sigma subunit are becoming
      clearer.

PMID- 15564658
TI  - Synthesis of Arg-Gly-Asp (RGD) sequence conjugated thermo-reversible gel via the
      PEG spacer arm as an extracellular matrix for a pheochromocytoma cell (PC12)
      culture.
AB  - Adhesion molecules composed of Gly-Arg-Gly-Asp-Ser (GRGDS) peptides and cell
      recognition ligands were inculcated into thermo-reversible hydrogel composed of N
      isopropylacrylamide, with a small amount of succinyl poly(ethylene glycol) (PEG)
      acrylate (MW 3400) used as a biomimetic extracellular matrix (ECM). The GRGDS
      containing p(NiPAAm-co-PEG) copolymer gel was studied in vitro for its ability to
      promote cell spreading and to increase the viability of cells by introducing PEG
      spacers. Hydrogel lacking the adhesion molecules proved to be a poor ECM for
      adhesion, permitting only a 20% spread of the seeded cells after 10 days. When
      PEG spacer arms, immobilized by a peptide linkage, had been integrated into the
      hydrogel, conjugation of RGD promoted cell spread by 600% in a 10-day trial. In
      addition, in a serum-free medium, only GRGDS peptides conjugated with the spacer
      arm were able to promote cell spread. In terms of the cell viability, GRGDS
      peptides conjugated with the PEG-carrying copolymer gel specifically mediated
      cell spread. This result supports the theory that specific recognition is the
      result of interaction between the integrin families on the fibroblast, and the
      RGD sequence on the p(NiPAAm-co-PEG) copolymer gel.

PMID- 15564659
TI  - Effect of a pore-forming protein derived from Flammulina velutipes on the Caco-2
      intestinal epithelial cell monolayer.
AB  - We have previously found a transepithelial electrical resistance (TEER)
      decreasing protein derived from Flammulina velutipes, which was revealed to be
      identical to flammutoxin (FTX) that is known as a hemolytic pore-forming protein.
      This protein induced a rapid decrease in TEER and parallel increase in
      paracellular permeability in the intestinal epithelial Caco-2 cell monolayer
      without any cytotoxicity. An immunoblotting analysis revealed that the FTX
      induced decrease in TEER was accompanied by the formation of a high-molecular
      weight complex on the surface of Caco-2 cells. Intracellular Ca(2+) imaging
      showed that exposure to FTX caused a rapid Ca(2+) influx. It was observed by
      electron microscopy that FTX induced swelling of microvilli and expansion of the
      cellular surface. Staining with fluorescent phalloidin showed a marked change to
      filamentous actin in the FTX-treated cells. These results suggest that TEER
      reduction could sensitively detect small membrane pore formation by FTX in the
      intestinal epithelium which causes a morphological alteration and disruption of
      the paracellular barrier function.

PMID- 15564660
TI  - Caffeoylsophorose, a new natural alpha-glucosidase inhibitor, from red vinegar by
      fermented purple-fleshed sweet potato.
AB  - The suppressive effect on the postprandial blood glucose rise through alpha
      glucosidase (AGH) inhibition was investigated in this study in order to clarify
      an antihyperglycemic function of 6-O-caffeoylsophorose (CS) from diacylated
      anthocyanin. The administration of CS (100 mg/kg) following maltose (2 g/kg) to
      Sprague-Dawley rats resulted in the maximal blood glucose level after 30 min
      being significantly decreased by 11.1% compared to the control. A reduction in
      the serum insulin secretion was also observed in parallel to the decrease in
      blood glucose level. No blood glucose change was apparent when sucrose or glucose
      was ingested, suggesting that the antihyperglycemic effect of CS was achieved by
      maltase inhibition, rather than by sucrase or glucose transport inhibition. An
      AGH inhibitory assay demonstrated that the non-competitive maltase inhibition of
      CS was partly due to acylation by phenolic acid with sugar, the presence of
      hydroxyl groups in the aromatic ring, and the presence of an unsaturated alkyl
      chain in the acylated moiety.

PMID- 15564661
TI  - Hydrophilic monolayer formation of adsorbed cationic starch and cationic
      hydroxyethyl cellulose derivatives on polyester surfaces.
AB  - Cationic starch, cationic cellulose derivatives, and hydrophobically modified
      cationic cellulose were physically adsorbed from aqueous solution onto oppositely
      charged hydrophobic polyester (poly(ethylene terephthalate)) fabric and nonwoven,
      and this resulted in hydrophilic surface properties. Surface coverage of the
      polysaccharides occurred primarily by strong electrostatic interactions, and the
      surface characteristics were evaluated by measuring the time required for a water
      droplet to be absorbed into the polyester material as well as by electron
      spectroscopy for chemical analysis (ESCA). From a comparison of the adsorption
      characteristics we assess the polysaccharide-dependent and substrate-dependent
      adsorption behavior and discuss the similarities and differences in the
      hydrophilic properties and wettability observed. In particular, the temperature
      of the cationic polysaccharide solutions in which the substrate was immersed, the
      configuration of the polymer in solution, and the presence of hydrophobic
      substituents on the cationic moiety have a considerable effect on the
      polysaccharide affinity and its adsorption on the surface, irrespective of the
      substrate type (fabric or nonwoven). We also evaluate the relative contribution
      of the polyelectrolyte molecular weight, concentration in solution, and degree of
      charge density along the polymer chain which determine the range of interactions
      and alter surface hydroplilicity dependent on the type of substrate.

PMID- 15564662
TI  - Improvement of insulin resistance and insulin secretion by water extracts of
      Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90%
      pancreatectomized rats.
AB  - The effect of supplementation with Phellinus linteus (P. linteus), Paecilomyces
      tenuipes (P. tenuipes), and Cordyceps militaris (C. militaris) mushroom water
      extracts on the insulin secretion and insulin resistance of 90% pancreatectomized
      (Px) male Sprague Dawley rats was investigated. Px rats were daily administered
      0.5 g of P. linteus, P. tenuipes, and C. militaris aqueous extracts or a placebo
      per 1 kg body weight with a 40% fat diet for 8 weeks. Fasting serum glucose
      levels were lower in rats receiving C. militaris than in the control group.
      Insulin secretion at the elevated serum glucose levels was lowest in rats that
      consumed P. tenuipes in hyperglycemic clamp. Whole body glucose disposal rates
      increased in C. militaris but decreased in P. tenuipes compared to those in the
      control group in euglycemic hyperinsulinemic clamp. The GLUT4 content and
      fraction velocity of glycogen synthase in the soleus and quadriceps muscles
      increased in the rats treated with C. militaris, but P. tenuipes decreased both.
      In sum, a water extract of C. militaris ameliorates insulin resistance by
      enhancing glucose utilization in skeletal muscles.

PMID- 15564663
TI  - Structure-activity relationship of S-benzylisothiourea derivatives to induce
      spherical cells in Escherichia coli.
AB  - We have previously reported that a novel S-benzylisothiourea derivative, S-(3,4
      dichlorobenzyl)isothiourea, tentatively named A22, induced spherical cells in
      Escherichia coli. To elucidate the structural element(s) required for inducing
      these spherical cells, the biological activity of S-benzylisothiourea derivatives
      and related compounds toward E. coli cells was investigated. S-(4
      Chlorobenzyl)isothiourea revealed spherical cell-inducing activity, although
      being slightly less potent than A22, and S-benzylisothiourea itself showed much
      less activity. S-Cyclohexylmethylisothiourea did not show antibacterial activity
      and had little effect on the cell shape. S-Heptylisothiourea showed antibacterial
      activity and induced elongated cells rather than spherical cells.
      Benzylisothiocyanate inhibited cell growth but did not induce spherical cells. S
      Ethylisothiourea, benzylthiocyanate, benzylisocyanate, and N-phenylthiourea did
      not show any activity under the present experimental conditions. These results
      indicate that the S-benzylisothiourea structure was necessary and sufficient for
      inducing spherical cells and that 3- and/or 4-chloro-substitution of the S-benzyl
      group enhanced this activity.

PMID- 15564664
TI  - Analysis of bgl operon structure and characterization of beta-glucosidase from
      Pectobacterium carotovorum subsp. carotovorum LY34.
AB  - A putative bgl operon of Pectobacterium carotovorum subsp. carotovorum LY34 (Pcc
      LY34) was isolated. Sequence analysis of the 5,557 bp cloned DNA fragment
      (accession no. AY542524) showed three open reading frames (bglT, bglP, and bglB)
      predicted to encode 287, 633, and 468 amino acid proteins respectively. BglT and
      BglP ORFs show high similarity to that of the Pectobacterium chrysanthemi ArbG
      antiterminator and ArbF permease respectively. Also, the latter contains most
      residues important for phosphotransferase activity. The amino acid sequence of
      BglB showed high similarity to various beta-glucosidases and is a member of
      glycosyl hydrolase family 1. The purified BglB enzyme hydrolyzed salicin,
      arbutin, pNPG, and MUG. The molecular weight of the enzyme was estimated to be
      53,000 Da by SDS-PAGE. The purified beta-glucosidase exhibited maximal activity
      at pH 7.0 and 40 degrees C, and its activity was enhanced in the presence of
      Mg(2+). Two glutamate residues (Glu(173) and Glu(362)) were found to be essential
      for enzyme activity.

PMID- 15564665
TI  - IL-10 augments antibody production in in vitro immunized lymphocytes by inducing
      a Th2-type response and B cell maturation.
AB  - An in vitro immunization (IVI) protocol enables antigen specific antibody
      production from L-Leucyl-L-Leucine methyl ester (LLME)-treated human peripheral
      blood lymphocytes (PBL) upon antigen stimulation in the presence of IL-2, IL-4,
      and muramyl dipeptide. In the course of our studies, we have found that IL-10
      added at the antigen sensitization significantly augmented antibody production
      level from the LLME-treated PBL. In the present study, we tried to demonstrate
      the role of IL-10 in the augmentation of antibody production in an IVI protocol
      by clarifying the cytokine expression profiles in CD4(+) and CD8(+) T cells. The
      results showed that IL-10 skewed the Th1/Th2 balance to Th2-type responses by
      suppressing Th1-type cytokine production and augmenting Th2-type cytokine
      production in CD4(+) and CD8(+) T cells, as well as in CD19(+) B cells.
      Furthermore, IL-10 augmented the expression of CD38, an antigen marker of plasma
      cells, on B cells, which clearly indicates that IL-10 promoted differentiation
      and maturation of B cells in an IVI protocol. These results indicate that IL-10
      plays an important role in setting the cellular milieu to produce antibodies in
      an IVI protocol.

PMID- 15564666
TI  - Maillard reaction rate in various glassy matrices.
AB  - The Maillard Reaction (MR) rate below the glass transition temperature (T(g)) for
      various model glassy food systems was studied at temperatures between 40 degrees
      C and 70 degrees C. As a sample, freeze-dried glucose and lysine systems embedded
      in various glassy matrices (e.g., polyvinylpyrrolodone and trehalose) were used,
      and the MR rate below the T(g) was compared among the various glassy matrices.
      The extent of MR was estimated spectrophotometrically from the optical density at
      280 nm (OD(280)), and the MR rate (k(280)) was determined as a pseudo zero order
      reaction rate from the time course of OD(280). Although k(280) was described by
      the Arrhenius plot, the temperature dependence of k(280) was almost the same and
      the intercept was different among the matrices. From the comparison of k(280), it
      was suggested that the MR rate in glassy matrix was affected not only by the
      T(g), but also by the hydrogen bonding between MR reactants and glassy matrix.

PMID- 15564667
TI  - Thermostable esterase from a thermoacidophilic archaeon: purification and
      characterization for enzymatic resolution of a chiral compound.
AB  - Homolog to lipolytic enzymes having the consensus sequence Gly-X-Ser-X-Gly, from
      the Sulfolobus solfataricus P2 genome, were identified by multiple sequence
      alignments. Among three potential candidate sequences, one (Est3), which
      displayed higher activity than the other enzymes on the indicate plates, was
      characterized. The gene (est 3) was expressed in Escherichia coli, and the
      recombinant protein (Est3) was purified by chromatographic separation. The enzyme
      is a trimeric protein and has a molecular weight of 32 kDa in monomer form in its
      native structure. The optimal pH and temperature of the esterase were 7.4 and 80
      degrees C respectively. The enzyme showed broad substrate specificities toward
      various p-nitrophenyl esters ranging from C2 to C16. The catalytic activity of
      the Est3 esterase was strongly inhibited by phenylmethylsulfonyl fluoride (PMSF)
      and diethyl p-nitrophenyl phosphate. Based on substrate specificity and the
      action of inhibitors, the Est3 enzyme was estimated to be a carboxylesterase (EC
      3.1.1.1). The enzyme with methyl (+/-)-2-(3-benzoylphenyl)propionate-hydrolyzing
      activity to (-)-2-(3-benzoylphenyl)propionic acid displayed a moderate degree of
      enantioselectivity. The product, (-)-2-(3-benzoylphenyl)propionic acid, rather
      than its methyl ester, was obtained in 80% enantiomeric excess (e.e.(p)) at 20%
      conversion at 60 degrees C after a 32-h reaction. This result indicates that S.
      solfataricus esterase can be used for application in the synthesis of chiral
      compounds.

PMID- 15564668
TI  - Molecular cloning of a gene encoding endo-beta-D-1,4-glucanase PCE1 from
      Phycomyces nitens.
AB  - We previously cloned three endoglucanase genes, rce1, rce2, and rce3, from
      Rhizopus oryzae as the first cellulase genes from the subdivision Zygomycota. In
      this study, an endoglucanase gene, designated a pce1 gene, was cloned by plaque
      hybridization with the codon usage-optimized rce1 gene as a probe from Phycomyces
      nitens, a member of the subdivision Zygomycota. The pec1 gene had an open reading
      frame of 1,038 nucleotides encoding an endoglucanase (PCE1) of 346 amino acid
      residues. The amino acid sequence deduced from the pce1 gene consisted of a
      cellulose-binding domain (CBD) at the N terminus and of a catalytic domain
      belonging to family 45 glycoside hydrolase at the C terminus. PCE1 was purified
      to apparent homogeneity from the culture supernatant of P. nitens and the
      molecular mass was found to be 45 kDa. The optimum pH for the CMCase activity of
      PCE1 was 6.0, and the optimum temperature was 50 degrees C, the lowest among the
      family 45 endoglucanases.

PMID- 15564669
TI  - Purification and characterization of alpha-keto amide reductase from
      Saccharomyces cerevisiae.
AB  - An NADPH-dependent alpha-keto amide reductase was purified from Saccharomyces
      cerevisiae. The molecular mass of the native enzyme was estimated to be 33 and 36
      kDa by gel filtration chromatography and SDS-polyacrylamide gel electrophoresis,
      respectively. The purified enzyme showed a reducing activity not only for
      aromatic alpha-keto amides but also for aliphatic and aromatic alpha-keto esters.
      The internal sequence of the enzyme was identical with that of a hypothetical
      protein (ORF YDL 124w) coded by yeast chromosome IV.

PMID- 15564670
TI  - Antioxidative activity of a zinc-chelating substance in coffee.
AB  - Coffee brew contains a brownish zinc-chelating polymer designated ApV. ApV was
      prepared from the precipitate formed in a solution of instant coffee by adding
      ZnCl(2) and purified using ion-exchange and cellulose column chromatographies.
      The antioxidative activities of ApV and related compounds were evaluated in this
      study. The free-radical scavenging activity of ApV estimated by ABTS assay was at
      a similar level to that of instant coffee, while the O(2)(-) scavenging activity
      of ApV, which is superoxide dismutase-like activity, was lower than that of
      instant coffee. The hydroxyl-radical scavenging activity of ApV was higher than
      that of instant coffee, and the auto-oxidation of linoleic acid was more strongly
      inhibited by ApV than by caffeic acid.

PMID- 15564671
TI  - Contribution of the second OB fold of ribosomal protein S1 from Escherichia coli
      to the recognition of TmRNA.
AB  - Escherichia coli ribosomal protein S1 is composed of six repeating homologous
      oligonucleotide/oligosaccharide-binding fold (OB folds). In trans-translation, S1
      plays a role in delivering transfer-messenger RNA (tmRNA) to stalled ribosomes.
      The second OB fold of S1 was found to be protected from tryptic digestion in the
      presence of tmRNA. Truncated S1 mutant Delta2, in which the first and second OB
      folds were deleted, showed significantly decreased tmRNA-binding activity.
      Furthermore, the E. coli S1 homolog (BS1) from Bacillus subtilis, which
      corresponds to the four C-terminal OB folds of E. coli S1, showed no interaction
      with E. coli tmRNA, as judged by the results of a gel shift assay. Surface
      plasmon resonance analysis revealed that mutant Delta2 and BS1 had decreased
      association rate constants (ka, 0.59 x 10(3) M(-1).S(-1); and ka, 1.89 x 10(3) M(
      1).S(-1)), while they retained the respective dissociation rate constants (kd,
      0.67 x 10(-3) S(-1); and kd, 0.53 x 10(-3) S(-1)), in comparison with wild-type
      protein S1 (ka, 3.32 x 10(3) M(-1).S(-1); and kd, 0.56 x 10(-3) S(-1)). These
      results suggest that the second OB fold in protein S1 is essential for the
      recognition of tmRNA, while the four C-terminal OB folds play a role in
      stabilizing the S1-tmRNA complex.

PMID- 15564672
TI  - Cysteine suppresses oxidative stress-induced myofibrillar proteolysis in chick
      myotubes.
AB  - The effects of cysteine as an antioxidant nutrient on change in protein
      modification and myofibrillar proteolysis in chick myotubes by induction of
      oxidative stress by H(2)O(2) treatment were investigated. Myotubes were treated
      for 1 h with H(2)O(2) (1 mM). After this treatment, the H(2)O(2) was removed and
      the cells were cultured in cysteine (0.1 and 1 mM) containing serum-free medium
      for 24 h. Protein carbonyl content as an index of protein modification and N(tau)
      methylhistidine release as an index of myofibrillar proteolysis were increased at
      24 h after H(2)O(2) treatment, and the increment was reduced by cysteine.
      Calpain, proteasome and cathepsin (B+L and D) activities were increased at 24 h
      after H(2)O(2) treatment, and the increment was also reduced by cysteine. These
      results indicate that cysteine suppresses protein modification by oxidative
      stress, resulting in a decrease of protease acitivities, finally resulting in a
      decrease in myofibrillar proteolysis in chick myotubes.

PMID- 15564673
TI  - Anti-tumor activity of an enzymatically synthesized alpha-1,6 branched alpha-1,4
      glucan, glycogen.
AB  - Oral administration of an enzymatically synthesized alpha-1,4:1,6-glycogen (ESG)
      at a dose of 50 mug/ml significantly prolonged the survival time of Meth A tumor
      bearing mice. ESG also significantly stimulated macrophage-like cells (J774.1),
      leading to augmented production of nitric oxide (NO) and tumor necrosis factor
      alpha (TNF-alpha). The weight-average degree of polymerization (DPw) and the
      ratio of branch linkage (BL) of ESG were 149,000 and 8.1% respectively. beta
      Amylase-treated ESG, however, lost J774.1-activating activity although inhibited
      subcutaneous growth of Meth A tumor cells admixed with it. Its DPw and BL changed
      to 126,000 and 20% respectively. Partially degraded amylopectin [(AP), DPw:
      110,000, BL; 5.1] was also effective at stimulating J774.1, but its activity was
      lower than that of ESG. Other alpha-glucans [cycloamylose (CA), enzymatically
      synthesized amylose (ESA), highly branched cyclic dextrin (HBCD), and beta
      amylase-treated HBCD], of which DPw was lower than that of ESG, showed no J774.1
      activating activity and weaker anti-tumor activity.

PMID- 15564674
TI  - Enzymatic synthesis of dehydro cyclo(His-Phe)s, analogs of the potent cell cycle
      inhibitor, dehydrophenylahistin, and their inhibitory activities toward cell
      division.
AB  - Cyclo(His-Phe) was effectively converted to its dehydro derivatives by the enzyme
      of Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types
      of dehydro derivatives were isolated from the reaction mixture and identified as
      cyclo(DeltaHis-DeltaPhe) and cyclo(His-DeltaPhe). This is the first report on
      cyclo(His-DeltaPhe) and the enzymatic preparation of both compounds.
      Cyclo(DeltaHis-DeltaPhe), a tetradehydro cyclic dipeptide, exhibited a minimum
      inhibitory concentration of 0.78 mumol/ml inhibitory activity toward the first
      cleavage of sea urchin embryos, in contrast to cyclo(His-DeltaPhe) that had no
      activity. The finding that the isoprenylated derivative of cyclo(DeltaHis
      DeltaPhe), dehydrophyenylahistin, had 2,000 times higher activity than
      cyclo(DeltaHis-DeltaPhe) indicates that an isoprenyl group attached to an
      imidazole ring of the compound was essential for the inhibitory activity.

PMID- 15564675
TI  - Localization of alpha-glucosidases I, II, and III in organs of European
      honeybees, Apis mellifera L., and the origin of alpha-glucosidase in honey.
AB  - Three kinds of alpha-glucosidases, I, II, and III, were purified from European
      honeybees, Apis mellifera L. In addition, an alpha-glucosidase was also purified
      from honey. Some properties, including the substrate specificity of honey alpha
      glucosidase, were almost the same as those of alpha-glucosidase III. Specific
      antisera against the alpha-glucosidases were prepared to examine the localization
      of alpha-glucosidases in the organs of honeybees. It was immunologically
      confirmed for the first time that alpha-glucosidase I was present in ventriculus,
      and alpha-glucosidase II, in ventriculus and haemolymph. alpha-Glucosidase III,
      which became apparent to be honey alpha-glucosidase, was present in the
      hypopharyngeal gland, from which the enzyme may be secreted into nectar gathered
      by honeybees. Honey may be finally made up through the process whereby sucrose in
      nectar, in which glucose and fructose also are naturally contained, is hydrolyzed
      by secreted alpha-glucosidase III.

PMID- 15564676
TI  - Tea catechin suppresses adipocyte differentiation accompanied by down-regulation
      of PPARgamma2 and C/EBPalpha in 3T3-L1 cells.
AB  - Obesity is a serious health problem, and its prevention is promoted through life
      style including diet and exercise. In this study, we investigated the suppressive
      effects of tea catechin on the differentiation of 3T3-L1 preadipocytes to
      adipocytes. (-)-Catechin 3-gallate (CG), (-)-epigallocatechin (EGC), (-)
      epicatechin 3-gallate, and (-)-epigallocatechin 3-gallate at 5 muM suppressed
      intracellular lipid accumulation. The suppressive effects of CG and EGC were
      stronger than the others, and CG and EGC also suppressed the activity of glycerol
      3-phosphate dehydrogenase as a differentiation marker. These catechins inhibited
      the expression of peroxisome proliferator-activated receptor (PPAR) gamma2 and
      CCAAT/enhancer-binding protein (C/EBP) alpha, both of which act as key
      transcription factors at an early stage of differentiation, followed by the
      expression of glucose transporter (GLUT) 4 at a later stage. In addition, the
      catechins did not affect the phosphorylation status of the insulin signal
      pathway. Thus, catechin suppressed adipocyte differentiation accompanied by the
      down-regulation of PPARgamma2, C/EBPalpha, and GLUT4. These results suggest that
      tea catechin prevents obesity through the suppression of adipocyte
      differentiation.

PMID- 15564677
TI  - Cloning and characterization of farnesyl diphosphate synthase from the rubber
      producing mushroom Lactarius chrysorrheus.
AB  - Farnesyl diphosphate is involved in rubber biosynthesis as an initiating
      substrate for both polyprenol and mushroom rubber. So far, we have isolated the
      cDNA of a farnesyl diphosphate synthase (FPS) for the first time from a rare
      rubber-producing mushroom, Lactarius chrysorrheus, by the degenerate RT-PCR
      technique based on sequence information of FPS genes from fungi and yeasts. The
      open reading frame was clarified to encode a protein of 381 amino acid residues
      with a calculated molecular weight of 42.9 kDa. The deduced amino acid sequence
      of L. chrysorrheus FPS showed about 50% identity with those of other fungi and
      yeasts as well as plants. We expressed the cDNA of L. chrysorrheus FPS in
      Escherichia coli as a glutathione-S-transferase (GST)-fusion protein. The
      purified obtained protein showed FPS activity in which geranyl diphosphate (GPP)
      served as primary substrate, with a 2.4-fold higher k(cat)/K(m) value for GPP
      than for dimethylallyl diphosphate (DMAPP).

PMID- 15564678
TI  - Transglycosylation activity of Dictyoglomus thermophilum amylase A.
AB  - Amylase A from Dictyoglomus thermophilum is a thermophilic enzyme and has about
      40% identity with 4-alpha-glucanotransferase (GTase) from Thermococcus litoralis,
      and both of these enzymes belong to family 57 glycosyl hydrolase. Since the
      transglycosylation activity of T. litoralis GTase has been well characterized,
      the substrate specificity and reaction products of amylase A from D. thermophilum
      were examined. alpha-1,4 Glucan was produced from maltooligosaccharides, and
      glucoamylase-resistant molecules (cycloamyloses) were produced from longer chain
      amylose (average molecular mass 200 kDa). It has been reported that amylase A
      from D. thermophilum hydrolyzes starch, but in this study it was found that the
      enzyme was also able to use maltooligosaccharides and long chain amylose as
      substrate and has transglycosylation activity.

PMID- 15564679
TI  - Towards structural determination of the ComX pheromone: synthetic studies on
      peptides containing geranyltryptophan.
AB  - Bacteria produce and respond to signal molecules depending on their cell density.
      This process is called "quorum sensing". The ComX pheromone, controlled by quorum
      sensing, activates natural genetic competence in Bacillus subtilis. ComX is an
      oligopeptide with a posttranslational modification. It has been suggested that
      ComX pheromone is modified with an isoprenoid at its tryptophan residue, but the
      complete chemical structure is unknown. We first determined the molecular formula
      of ComX(RO-E-2), a competence factor for B. subtilis strain RO-E-2. Then we
      synthesized putative pheromones with 1-, 2-, 4-, 5-, 6-, or 7-geranyl substituted
      tryptophan residues. The regio- and stereo-selective synthesis of the geranyl
      tryptophans was successful, and we prepared the six peptides with modified
      tryptophan residues. These peptides had the same molecular formula and showed
      similar hydrophobicity to the natural ComX(RO-E-2) in LC-MS analysis. But, none
      of them showed the same retention time as the natural pheromone and none
      exhibited its biological activity. These results suggest that the isoprenoid
      modification pattern of the tryptophan residue is more complex than postulated.

PMID- 15564680
TI  - Effects of egg yolk proteins on the longitudinal bone growth of adolescent male
      rats.
AB  - Hen egg is a nutritional store for a new life. We examined the effect of egg yolk
      proteins on longitudinal bone growth in the rat. Protein fractions from egg yolk
      were tested. Milk protein, casein, was used as a control. The bone growth rate
      was significantly increased by yolk water-soluble protein (YSP, 100 mg/kg)
      administration for 5 d. The bone morphogenetic protein-2 immunostaining of growth
      plate was also increased. Considering the results, YSP can be used as a growth
      promoting factor.

PMID- 15564681
TI  - Comparative study on the modulation of IgE and cytokine production by Phellinus
      linteus grown on germinated brown Rice, Phellinus Linteus and germinated brown
      rice in murine splenocytes.
AB  - We compared the immunomodulating activities in mice of extracts from Phellinus
      linteus grown on germinated brown rice (PB), Phellinus linteus (PL) alone, and
      germinated brown rice (BR) alone. The PL, BR and PB-treated mice were
      administered with the respective extract (2 mg/head/day) by oral gavage for 4
      weeks. All extracts markedly decreased the IgE production and allergic responses
      in serum and splenocytes. PL and PB increased the proportion of CD4(+) but not
      CD8(+) T cells in splenocytes. Cytokine production was significantly augmented in
      all treated mice; the concentration of IFN-gamma was greater in the PL, BR and PB
      mice than in the control group. The concentration of IL-10 was lower in the BR
      group than in the other groups. These results may be related to the suppression
      of IgE production. We conclude that PB modulated the immune responses of IgE
      production and Th1/Th2 cytokine secretion in murine splenocytes.

PMID- 15564682
TI  - Proteasome inhibitors induce changes in chromatin structure characteristic of
      senescent human fibroblasts.
AB  - Inhibitors of proteasome induced premature senescence in normal human
      fibroblasts. Besides morphological alteration and expression of senescence marker
      genes, these cells manifested senescence-associated heterochromatic foci under
      staining of the nuclei with DAPI similar to normally senescent cells. These
      results suggest that declining ability in protein degradation may be involved in
      the formation of heterochromatic foci in senescent fibroblasts.

PMID- 15564683
TI  - Synthesis and antinematodal activity of 3-n-alkylphenols.
AB  - Several 3-alkylphenols including 3-undecylphenol, which was isolated from a
      Sumatran rainforest plant, were synthesized to investigate their antinematodal
      activity against the phytopathogenic nematodes, Bursapherencus xylophilus. A
      three-step synthesis involving the treatment of 2-cyclohexen-1-one with the
      Grignard reagent, oxidation of the resulting 1-alkyl-2-cyclohexen-1-ol and
      subsequent aromatization of 3-alkyl-2-cyclohexen-1-one successfully afforded such
      phenols. Among the 3-alkylphenols, 3-nonylphenol showed the highest activity,
      while 3-decylphenol and 3-undecylphenol also showed high activity.

PMID- 15564684
TI  - Increased levels of policosanol and very long-chain fatty acids in potato pulp
      fermented with Rhizopus oryzae.
AB  - Significant amounts of policosanol and very long-chain fatty acids (VLFAs)
      ranging in carbon length from 22 to 30 were found in the lipophilic fraction
      obtained from potato pulp fermented with Rhizopus oryzae. It is believed that
      these compounds would have originally been present as suberin-related compounds,
      but not as wax, in the periderm of potato tubers and concentrated into potato
      pulp during the process of starch production. Moreover, the policosanol and VLFAs
      extracted from potato pulp with organic solvents were found to have increased
      after fermentation.

PMID- 15564685
TI  - Growth promotion of mycelia of the Matsutake mushroom Tricholoma matsutake by D
      isoleucine.
AB  - Mycelial growth of the Matsutake mushroom (Tricholama matsutake) was much slower
      than that of the other mushroom species. We found that the addition of D
      isoleucine to the culture medium strikingly promoted mycelia growth. The other
      amino acids tested had no effect on this growth promotion.

PMID- 15564686
TI  - Identification of peptidyl mimics of bioactive gibberellin recognized by an
      antibody.
AB  - We screened a phage display peptide library for peptidyl mimotopes of gibberellin
      against anti-bioactive gibberellin antibody. The peptides obtained were grouped
      into two homologous sequences and their binding to the antibody was put in
      competition with free GA(4) but not with GA(4) methylester, suggesting that the
      peptides behave as mimics of GA(4). As an application, the phage display peptide
      was shown to work as a tracer for enzyme-linked immunosorbent assay (ELISA)
      analysis of GA(4).

PMID- 15564687
TI  - Effects of alkalinization and ATPase inhibition on stromal free Mg2+
      concentration in spinach chloroplasts.
AB  - Our earlier studies indicate that stromal alkalinization is essential for light
      induced increase in free Mg(2+) concentration ([Mg(2+)]) in chloroplast. Stromal
      [Mg(2+)] was increased by dark incubation of chloroplasts in the K(+)-gluconate
      medium (pH 8.0), or by NH(4)Cl. These results indicate that stromal
      alkalinization can induce an increase in stromal [Mg(2+)] without illumination.
      Some inhibitors of envelope proton-translocating ATPase activity involved in H(+)
      efflux inhibited the alkalinization-induced increase in [Mg(2+)].

PMID- 15564688
TI  - Docosahexaenoic acid induces apoptosis via the Bax-independent pathway in HL-60
      cells.
AB  - We attempted to determine whether docosahexaenoic acid (DHA)-induced apoptosis is
      mediated via the Bax-mediated pathway in human myeloid leukemia HL-60 cells. DHA
      induced apoptosis was confirmed by morphological analysis and caspase-3
      activation. But, cyclosporin A (CsA), an inhibitor of mitochondrial permeability
      transition (MPT), did not inhibit DHA-induced Bax translocation to mitochondria
      or caspase-3 activation. These data suggest that DHA can induce apoptosis via the
      Bax-independent pathway.

PMID- 15564689
TI  - Phaeoside, a novel galactoside of hydroxymanoyl oxide from the gibberellin A1
      producing Phaeosphaeria sp. L487.
AB  - Isolation and examination of a diterpene glycoside from the culture filtrate of
      the gibberellin A(1)-producing Phaeosphaeria sp. L487 allowed us to identify a
      novel fungal galactoside of hydroxymanoyl oxide together with (-)-ent-13-epi
      manoyl oxide. It was designated phaeoside and determined to be 1alpha-hydroxy-ent
      13-epi-manoyl oxide 1-O-beta-D-galactopyranoside based on its chemical
      degradation and spectroscopic methods. This is the first report of the isolation
      of a diterpene galactoside from fungi.

PMID- 15564690
TI  - Novel pathophysiological insight and treatment strategies for heart failure-
      lessons from mice and patients--.
AB  - The ultimate goal of heart failure (HF) treatment is to improve the prognosis of
      patients. Previous basic, clinical, and population studies have advanced the
      modern treatment of HF, but efficacy is still limited especially in 'real world'
      patients. There are 2 approaches to solve this crucial issue. First is the
      further development of novel therapeutic strategies based on new insight into the
      pathophysiology of myocardial remodeling and failure. Second is the improvement
      of the quality of care in routine clinical practice. The basic approach is to
      develop the treatment of myocardial remodeling by regulating mitochondrial
      oxidative stress. In the failing heart, oxygen radicals are the result of defects
      of mitochondrial electron transport, causing mitochondrial DNA damage and
      functional decline, and further production of oxygen radicals. Oxidative stress
      causes myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating
      matrix metalloproteinases, all of which result in myocardial remodeling and
      failure. Therefore, mitochondrial oxidative stress and DNA damage are good
      therapeutic targets. The clinical approach is to develop effective strategies of
      HF management for the 'real world' patients. Readmission because of exacerbation
      is common in HF patients and further impairs their quality of life. Noncompliance
      with treatment is the most common precipitating factor for readmission. Regular
      medical follow-up and social support are important components that should be
      included in the disease management program of HF patients. These basic and
      clinical approaches are needed to establish new and effective treatment
      strategies for Japanese patients with HF.

PMID- 15564691
TI  - Potential candidates for cardiac resynchronization therapy in Japanese patients
      with idiopathic dilated cardiomyopathy--a Niigata multicenter study of DCM--.
AB  - BACKGROUND: The purpose of this study was to assess the candidates suitable for
      cardiac resynchronization therapy (CRT) and to examine the significance of the
      QRS duration in Japanese patients with idiopathic dilated cardiomyopathy (DCM).
      METHODS AND RESULTS: The study population consisted of 357 patients. The
      selection criteria for candidates suitable for CRT were QRS duration =130 ms,
      left ventricular ejection fraction (LVEF) =35% and New York Heart Association
      (NYHA) functional class III or IV by ACC/AHA/NASPE 2002 guidelines. We divided
      the study population into 2 groups: group A with a QRS duration <130 ms, and
      group B with a QRS duration =130 ms. In 25 of the 375 patients (7.0%), all the
      criteria were fulfilled. Group B had a significantly larger left ventricular
      diameter end-diastole and end-systole than group A (P<0.0001). Group B had a
      lower LVEF (P<0.0001). There was a fair inverse correlation (r=-0.58, P<0.0001)
      between the length of the QRS duration and LVEF. CONCLUSION: Approximately 7% of
      the Japanese patients with DCM are CRT candidates. In the present study, we found
      that prolonged QRS duration was associated with poor systolic function.

PMID- 15564692
TI  - Long-term beneficial effect of infarct-related artery patency in acute anterior
      myocardial infarction in patients with poor myocardial viability in the region-at
      risk.
AB  - BACKGROUND: Several studies have demonstrated the benefit of the patency of
      infarct-related artery (IRA) in acute myocardial infarction (AMI). However those
      studies have not been concerned with myocardial viability in the region-at-risk.
      In the present study the effect of the patency of IRA was investigated in the
      setting of anterior AMI with poor viable myocardium in the risk region. METHODS
      AND RESULTS: From 1993 to 1996 patients with a first time anterior AMI and poor
      viable myocardium in the region-at-risk at 1 month after onset were identified
      and enrolled. Patients with a totally occluded IRA were included in the Non-Open
      group (n=44), and patients with a reperfused IRA were included in the Open group
      (n=49). At 5 years after onset, left ventricular function was better preserved in
      the Open group than in the Non-Open group (p<0.05). Kaplan-Meier survival curves
      for cardiac mortality and event-free survival curves revealed poor prognoses in
      the Non-Open group over a 5-year period (p<0.05, respectively). The advantages of
      a patent IRA were further seen in health-related quality-of-life outcomes
      (p<0.05). CONCLUSIONS: Even in patients with poor myocardial viability after an
      anterior AMI, the patency of the IRA is strongly associated with improved long
      term survival, independent of residual myocardium viability.

PMID- 15564693
TI  - Relationship between the generation and the facilitated percutaneous coronary
      intervention in patients with acute myocardial infarction--analysis based on the
      fibrinolysis and subsequent transluminal trial--.
AB  - BACKGROUND: The purpose of the present study was to evaluate the efficacy and
      safety of facilitated percutaneous coronary intervention (PCI) in comparing young
      and elderly patients with acute myocardial infarction. METHODS AND RESULTS: The
      present study enrolled 168 initial myocardial infarction patients within 12 h of
      the symptom onset between 40 and 80 years of age who were indicated on the
      fibrinolysis and subsequent transluminal (FAST-3) trial. The patients were
      divided into 4 groups according to their age, peak creatine kinase (CK), peak CK
      MB and peak troponin T (Tn-T) levels, and cardiac function were compared between
      the 4 groups. There were no differences between the 4 groups in terms of the time
      from arrival at the emergency room (ER) to the achievement of TIMI-3 patency.
      There were also no significant differences between the 4 groups in terms of the
      peak CK, peak CK-MB or peak Tn-T levels. Furthermore, there were no significant
      differences between the 4 groups in terms of the mortality rate or the incidence
      of hemorrhagic complications at 30 days. CONCLUSIONS: Facilitated PCI is
      considered to have an important potential role in the treatment of myocardial
      infarction in Japan, in which the age of the population is steadily increasing.

PMID- 15564694
TI  - Effect of smoking on endothelial function and wall thickness of brachial artery.
AB  - BACKGROUND: Impaired flow mediated dilatation (FMD) and increased wall thickness
      (WT) of the brachial artery have been associated with atherosclerosis and its
      risk factors. In this study we sought to determine brachial artery wall thickness
      in chronic smokers and the instantaneous effect of smoking on brachial artery
      endothelium dependent vasodilator function in smokers and non-smokers. METHOD AND
      RESULTS: Using a high-resolution ultrasound, WT of posterior brachial artery
      wall, the diameter of brachial artery at rest and during reactive hyperemia (FMD
      %), as well as after sublingual administration of nitroglycerine (nitroglycerine
      mediated dilatation (NMD) %) was measured in 20 smokers and 20 non-smokers. Wall
      thickness (WT) of the posterior brachial artery wall and the wall index (WI) were
      greater in smokers than non-smokers. The baseline brachial artery diameter was
      comparable in smokers and non-smokers. Flow mediated dilation (FMD) was found to
      be less in smokers than non-smokers. The NMD in smokers also did not differ
      significantly from that in non-smokers. Flow mediated dilation significantly
      reduced after smoking compared to baseline in both groups. However, NMD remained
      unchanged after smoking in both groups. CONCLUSIONS: Increased WT and impaired
      endothelium-dependent dilatation of brachial artery suggests that cigarette
      smoking disrupts vessel wall morphology long before atherosclerosis is manifest.

PMID- 15564695
TI  - Acute cigarette smoking-induced hemodynamic alterations in the common carotid
      artery--a transcranial Doppler study--.
AB  - BACKGROUND: Cigarette smoking has been shown to temporarily alter cerebral flow
      velocity and vasomotor reactivity, so the aim of this study was to assess the
      acute effects of smoking a single cigarette on the common carotid artery (CCA)
      hemodynamics in healthy nonsmokers. METHOD AND RESULTS: Using a 7.0 MHz linear
      transducer of a computed sonography system, the CCA hemodynamics, including the
      diameter of the left and right CCA, peak systolic velocity, maximum end-diastolic
      velocity, time-averaged maximum velocity pulsatility index, resistivity index,
      flow volume, diameter and area of the CCAs, were measured in 16 healthy
      nonsmokers before and immediately after smoking a cigarette. Compared with the
      baseline, heart rate and blood pressure significantly increased, the diameter,
      flow volume and area of each CCA were unchanged, and the pulsatility index and
      resistivity index were significantly altered after smoking. In addition, the peak
      systolic velocity, maximum end-diastolic velocity and time-averaged maximum
      velocity were significantly altered after smoking. CONCLUSIONS: Cigarette smoking
      significantly altered the CCA hemodynamics in nonsmokers, probably as a
      consequence of enhanced adrenergic activity.

PMID- 15564696
TI  - Is the ratio of transmitral peak E-wave velocity to color flow propagation
      velocity useful for evaluating the severity of heart failure in atrial
      fibrillation?
AB  - BACKGROUND: Although analysis of the transmitral inflow (TMF) pattern is widely
      used for evaluating left ventricular diastolic function and provides valuable
      information for the management of heart failure (HF) in sinus rhythm, its utility
      in patients with atrial fibrillation (AF) has not been established. The aim of
      this study was to investigate the relationship between the ratio of transmitral
      peak E-wave velocity to flow propagation velocity (E/Vp) obtained by a newly
      developed dual Doppler system and the plasma B-type natriuretic peptide (BNP)
      concentration or pulmonary capillary wedge pressure (PCWP) for evaluating the
      severity of heart failure with AF. METHODS AND RESULTS: In 68 patients with AF,
      the E/Vp was compared with plasma BNP concentration and PCWP. A cutoff value of >
      or =1.7 for E/Vp predicted a plasma BNP concentrationl of > or =200 pg/ml, with
      80% sensitivity and 84% specificity. Only E/Vp was found to be independently
      significant by stepwise multilinear regression analysis (r=0.40, p=0.01). PCWP
      values had good correlation with E/Vp (r=0.63, p<0.01) and were significantly
      higher in the group with E/Vp >/=1.7 (16+/-6 mmHg vs 11+/-4 mmHg, p<0.05).
      CONCLUSION: The Doppler-derived index of E/Vp correlated well with the
      neurohormonal and hemodynamic parameters, and was useful for evaluating the
      severity of heart failure with AF.

PMID- 15564697
TI  - Drug-induced changes in fibrillation cycle length and organization index can
      predict chemical cardioversion of long-lasting atrial fibrillation with bepridil
      alone or in combination with aprindine.
AB  - BACKGROUND: The aim of this study was to investigate whether drug-induced changes
      in fibrillation wave characteristics can predict pharmacological conversion of
      long lasting persistent atrial fibrillation (AF). METHODS AND RESULTS: The study
      group comprised 23 consecutive patients with AF lasting > or =1 month. Patients
      first received bepridil (200 mg/day) for 2-4 weeks. When sinus rhythm was not
      restored with bepridil, oral aprindine (40 or 60 mg/day) was added to bepridil.
      Fast Fourier transform analysis of fibrillation waves using lead V1 was performed
      to calculate the fibrillation cycle length (FCL). The spectral areas were
      measured and the maximum area divided by the total area was termed the
      fibrillation organization index (FOI). Sinus rhythm was restored in 16 of 23
      patients (70%); 8 of these 16 patients received only bepridil (Group I) and the
      other 8 responders received bepridil and aprindine (Group II). In Group I
      bepridil increased both FCL (p<0.001) and FOI (p<0.01) and terminated AF after
      20+/-12 days. In Group II bepridil increased FCL (p<0.001), but did not change
      FOI. The addition of aprindine terminated AF in association with an increase in
      both FCL (p<0.005) and FOI (p<0.005) within 19+/-8 days. In the remaining 7
      patients who did not have restoration of sinus rhythm, bepridil increased both
      FCL and FOI significantly, but less than in Group I, and the addition of
      aprindine did not further increase either of them. Chemical cardioversion of AF
      occurred in all patients with FCL > or =190 ms and FOI > or =45% after drug
      administration. CONCLUSION: Bepridil alone or in combination with aprindine
      converted long lasting persistent AF in association with an increase in both FCL
      and FOI. The combination of FCL and FOI after drug administration is helpful in
      predicting chemical cardioversion of persistent AF.

PMID- 15564698
TI  - Effects of repeated sauna treatment on ventricular arrhythmias in patients with
      chronic heart failure.
AB  - BACKGROUND: The aim of the present study was to determine whether repeated 60
      degrees C sauna treatment improves cardiac arrhythmias in chronic heart failure
      (CHF) patients, because ventricular arrhythmias are an important therapeutic
      target in CHF. METHODS AND RESULTS: Thirty patients (59+/-3 years) with New York
      Heart Association functional class II or III CHF and at least 200 premature
      ventricular contractions (PVCs)/24 h assessed by 24-h Holter recordings were
      studied. They were randomized into sauna-treated (n=20) or non-treated (n=10)
      groups. The sauna-treated group underwent a 2-week program of a daily 60 degrees
      C far infrared-ray dry sauna for 15 min, followed by 30 min bed rest with
      blankets, for 5 days per week. Patients in the non-treated group had bed rest in
      a temperature-controlled room (24 degrees C) for 45 min. The total numbers of
      PVCs/24 h in the sauna-treated group decreased compared with the non-treated
      group [848+/-415 vs 3,097+/-1,033/24 h, p<0.01]. Heart rate variability (SDNN,
      standard deviation of normal-to-normal beat interval) increased [142+/-10 (n=16)
      vs 112+/-11 ms (n=8), p<0.05] and plasma brain natriuretic peptide concentrations
      decreased [229+/-54 vs 419+/-110 pg/ml, p<0.05] in the sauna-treated group
      compared with the non-treated group. CONCLUSION: Repeated sauna treatment
      improves ventricular arrhythmias in patients with CHF.

PMID- 15564699
TI  - Electrophysiological characteristics and radiofrequency ablation of accessory
      pathways with slow conductive properties.
AB  - BACKGROUND: Atrioventricular accessory pathways (AP) with unusually long
      ventriculo-atrial (VA) conduction times are present in a significant subset of
      patients with the Wolff-Parkinson-White (WPW) syndrome, not including patients
      with the permanent form of atrioventricular junctional reciprocating tachycardia.
      METHODS AND RESULTS: We compared the electrophysiological characteristics and
      outcomes after radiofrequency (RF) ablation in 34 patients with the WPW syndrome,
      a VA interval >80 ms, and paroxysmal tachycardia with an RP/PR ratio <1 (the slow
      group), vs 80 patients with WPW syndrome and a VA interval <80 ms (the fast
      group). AP were found in the posteroseptal region significantly more often in the
      slow than in the fast group. In addition, the decremental conductive properties
      of the AP were more common in the slow than in the fast group. Catheter ablation
      of AP was highly successful in both groups, although ablation required a greater
      number of RF applications and longer procedure times in the slow group,
      especially for AP with decremental conductive properties. CONCLUSIONS: A
      posteroseptal AP location was more common in AP associated with long conduction
      times than in AP with typical conductive properties. Both types of AP were
      successfully ablated, although the slow group required longer procedures and more
      RF energy deliveries.

PMID- 15564700
TI  - Combined measurements of cardiac troponin T and N-terminal pro-brain natriuretic
      peptide in patients with heart failure.
AB  - BACKGROUND: To examine the prognostic contribution of combined cardiac troponin T
      (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with
      heart failure (CHF) in the absence of acute coronary syndrome. METHODS AND
      RESULTS: Between July 2001 and March 2002, 71 consecutive patients (mean age =
      68.4+/-1.4 years, 37 men), hospitalised for heart failure, were studied during
      hospitalisation and follow up until December 2002. Serum cTnT and NT-proBNP were
      measured on admission. Actuarial rates of adverse cardiac events, including
      sudden or CHF death, or rehospitalisation for CHF during follow up were compared
      with patients grouped according to initial serum cTnT and/or NT-proBNP
      concentrations. The adverse cardiac event-free rate among the 20 patients with
      cTnT > or 0.01 ng/ml was significantly lower than the 51 patients with cTnT <0.01
      ng/ml (P<0.05). Similarly, the adverse cardiac event-free rate among the 36
      patients with NT-proBNP > or =1,357 pg/ml (median) was significantly lower than
      the 35 patients with NT-proBNP <1,357 pg/ml (P<0.01). The 16 patients with high
      concentrations of both cTnT and NT-proBNP had a lower adverse cardiac event-free
      rate than the 31 patients with low cTnT and low NT-proBNP upon commencement of
      the study (P<0.005). CONCLUSION: Measurements of serum cTnT and NT-proBNP were
      reliable prognostic markers of adverse cardiac event in patients with CHF.

PMID- 15564701
TI  - Association between small dense low-density lipoprotein and postprandial
      accumulation of triglyceride-rich remnant-like particles in normotriglyceridemic
      patients with myocardial infarction.
AB  - BACKGROUND: Although the small dense low-density lipoprotein (sd-LDL) is
      associated with hypertriglyceridemia, more than 60% of myocardial infarction (MI)
      patients are normotriglyceridemic in the fasting state. This study was aimed to
      investigate the relationship between the low-density lipoprotein (LDL) phenotype
      and postprandial hyperlipemia (PPL) in MI patients. METHODS AND RESULTS: Oral fat
      tolerance tests were performed in 71 patients with acute MI and fasting
      triglyceride concentrations below 200 mg/dl. Postprandial changes in the LDL
      particle diameter (LDL-PD) and lipids over a 6-h period after a meal were
      compared among 4 groups of patients classified according to fasting triglyceride
      levels (A, B as <150, and C, D as > or =150) and postprandial triglyceride levels
      (A, C as <230 and B, D as > or =230). Although fasting concentrations of
      triglyceride and remnant-like particle (RLP)-triglyceride were significantly
      higher in group C than in group B, the areas under the curves of the RLPs were
      significantly higher in group B. The triglyceride-to-cholesterol ratio in the
      RLPs was significantly higher in the PPL group than in the nonPPL group
      postprandially. The prevalence of sd-LDL (LDL-PD < or =25.5 nm) was significantly
      higher in group D but similar between groups B and C (23%, 42%, 50% and 83% in
      groups A, B, C and D, respectively). CONCLUSION: These results suggest that
      postprandial accumulation of triglyceride-rich lipoproteins is strongly
      associated with sd-LDL in MI patients without hypertriglyceridemia.

PMID- 15564702
TI  - Leg fat percentage correlates negatively with coronary atherosclerosis.
AB  - BACKGROUND: Visceral fat is related to coronary atherosclerosis, but little is
      known about the relation between coronary atherosclerosis and percent body fat
      accumulated in different parts of the body. METHODS AND RESULTS: The subjects
      were 100 consecutive patients with demonstrated electrocardiographic ischemic
      changes. Coronary atherosclerosis was assessed using Gensini's coronary score
      (CS), and for body fat distribution dual energy X-ray absorptiometry was used.
      The parameters measured were serum lipid concentrations, body weight, body mass
      index, percent total fat, trunk fat percent, arm fat percent and leg fat percent.
      Trunk fat percent correlated significantly with CS (p<0.01), and concentrations
      of low-density lipoprotein cholesterol (LDL-C) (p<0.01) and very low-density
      lipoprotein cholesterol (VLDL-C) (p<0.05) in men and women. Leg fat percent
      correlated negatively with CS in both men and women (p<0.01 for each).
      Concentrations of both LDL-C and VLDL-C correlated positively with CS in both men
      and women (p<0.01). CONCLUSION: There is a difference between the effect of body
      fat in the legs and the trunk that suggests leg fat has an anti-atherosclerotic
      effect and a negative correlation with CS, and conversely, that trunk fat has a
      pro-atherosclerotic effect and correlates positively with CS.

PMID- 15564703
TI  - Arterial switch operations for single coronary artery ostium or intramural
      coronary artery.
AB  - BACKGROUND: Successful transfer of the coronary arteries is the most critical
      step during arterial switch operations for patients with transposition of the
      great arteries with a single coronary artery ostium and/or intramural coronary
      arteries. Various techniques have been reported and the present study was an
      evaluation of them in 10 neonatal patients. METHODS AND RESULTS: Coronary artery
      transfers are achieved by implantation of coronary buttons to the previously
      anastomosed neo-aorta using pericardial or pulmonary artery hood techniques. One
      patient died perioperatively because of myocardial malperfusion. Following
      prolonged mechanical ventilation, another died from sepsis on the 28th
      postoperative day. Coronary artery perfusion abnormality was not observed in the
      remaining patients. CONCLUSIONS: Transfer of the coronary button by the
      pericardial or pulmonary artery hood augmentation technique to the previously
      anastomosed neo-aorta is a practical, easy and convenient combination of methods
      for the treatment of these patients.

PMID- 15564704
TI  - Hospital and mid-term outcomes in elderly patients under-going off-pump coronary
      artery bypass grafting--comparison with younger patients--.
AB  - BACKGROUND: Clinical outcomes and problems following off-pump coronary artery
      bypass grafting (OPCAB) in elderly patients have not been clarified. METHODS AND
      RESULTS: The surgical results of elderly patients aged 75 years or older (n=50;
      38 males, mean age, 78.8 years) were reviewed and compared with those of younger
      patients (n=95; 79 males, mean age, 63.0 years). The EuroSCORE score was 6.9+/
      3.5 in the elderly group and 3.0+/-2.4 in the younger group (p<0.0001). There
      were no hospital deaths in either group. There was no significant difference in
      the postoperative complication rate except for atrial fibrillation (40.0% elderly
      vs 24.2% younger, p=0.0479). Postoperative intensive care unit and hospital stays
      did not differ. The frequency of blood transfusion was significantly higher in
      the elderly group (78.0% elderly vs 37.2% younger, p<0.0001). During the mean
      follow-up of 18.6+/-8.8 months, there was 1 sudden death in the elderly group,
      but no cardiac deaths in either group. The 32-month cardiac event-free and
      survival rates were similar for the 2 groups. CONCLUSION: OPCAB provides
      satisfactory clinical outcomes for elderly as well as younger patients.

PMID- 15564705
TI  - Clinical application of bone marrow implantation in patients with
      arteriosclerosis obliterans, and the association between efficacy and the number
      of implanted bone marrow cells.
AB  - BACKGROUND: There have been a number of recent reports on the use of autologous
      bone marrow implantation (BMI) in the treatment of peripheral arterial disease,
      with a clinical response rate of approximately 70%. However, the factors that
      influence efficacy have not yet been clarified. We have analyzed the relationship
      between the number of implanted bone marrow cells and the clinical efficacy of
      BMI. METHODS AND RESULTS: Eight patients with arteriosclerosis obliterans were
      treated with BMI. Bone marrow was aspirated from the ilium (500-1,000 ml), the
      mononuclear cells were separated and then were implanted. The clinical
      effectiveness of BMI was evaluated by assessing changes in the ankle-brachial
      pressure index (ABI) and the transcutaneous oxygen pressure (TcO2) between the
      pre-treatment baseline, with follow-up testing at 4 weeks. These changes were
      defined as DeltaABI and DeltaTcO2. The mean number of CD34-positive cells was
      1.04+/-0.60 x10(6) /kg body weight. There was a strong correlation between the
      number of CD34-positive cells and DeltaABI (r=0.754, p=0.028). CONCLUSIONS: It is
      likely that the number of implanted CD34-positive cells is one of the primary
      factors that influence the clinical efficacy of BMI.

PMID- 15564706
TI  - Angiotensin II receptor blocker prevents increased arterial stiffness in patients
      with essential hypertension.
AB  - BACKGROUND: High pulse wave velocity (PWV) is related to cardiovascular risk in
      essential hypertension (EHT). It is reported that short-term treatment with an
      angiotensin II receptor blocker (ARB) decreases PWV, as well as blood pressure
      (BP), and increases the serum adiponectin, known as an adipocytokine, which has
      an anti-atherosclerotic effect. However, it is not known whether long-term
      treatment with ARB prevents the increase in PWV independently of the reduction of
      BP, and whether adiponectin is related to the chronic effect of ARB on PWV.
      METHODS AND RESULTS: In order to examine the short-term effect of ARB on PWV, 9
      subjects with EHT had PWV measured before and after treatment with an ARB for 1
      month. The treatment significantly reduced PWV and BP. For evaluation of the long
      term effect of ARB therapy, 56 consecutive subjects with EHT who were already
      taking anti-hypertensive drugs other than an angiotensin-converting enzyme
      inhibitor had their PWV measured. We divided the EHT subjects into 2 groups: (1)
      the ARB group (EHT treated with an ARB for at least 6 months) and (2) the control
      group (EHT treated with anti-hypertensive drugs other than an ARB). Although
      there was no significant difference between the 2 groups in BP, age or body mass
      index, the PWV value in the ARB group was significantly lower than that in the
      control group. Moreover, the serum adiponectin concentration in the ARB group was
      significantly higher than that in the control group. CONCLUSIONS: Long-term
      treatment with ARB inhibits the progression of arterial stiffness independent of
      BP reduction. One of the mechanisms may be related to the increased serum
      adiponectin concentration after treatment with an ARB.

PMID- 15564707
TI  - Sapporo Fitness Club Trial (SFCT)--design, recruitment and implementation of a
      randomized controlled trial to test the efficacy of exercise at a fitness club
      for the reduction of cardiovascular risk factor--.
AB  - BACKGROUND: The annual health check followed by lifestyle recommendations has
      long been the standard national strategy to improve cardiovascular disease (CVD)
      risk factors in Japan. Exercise at fitness clubs, now widely accessible in major
      cities, has a novel appeal as a strategy with the additive effect of CVD risk
      reduction. The Sapporo Fitness Club Trial (SFCT) is a randomized controlled trial
      to compare the efficacy of the national standard alone (control) with the
      standard plus exercise at a fitness club (intervention) for the reduction of CVD
      risk factors. METHODS: The SFCT has recruited and randomized 561 relatively
      inactive overweight men and women, aged 40-85 years, with elevated levels of 2 or
      more of the following: systolic blood pressure, fasting blood glucose, and low
      density lipoprotein cholesterol. The intervention group was required to exercise
      at a fitness club 2-4 times per week. At the end of 6 months, risk factors,
      aerobic capacity, health-related quality of life measures, and adverse effects
      are to be compared. CONCLUSION: The SFCT is expected to have a major impact in
      Japan on public health recommendations on exercise for the reduction of lifestyle
      related disease.

PMID- 15564708
TI  - Differences in the changing trends of monophasic action potential duration and
      effective refractory period of the ventricular myocardium after myocardial
      infarction in vivo.
AB  - BACKGROUND: The relationship between monophasic action potential duration (MAPD)
      and effective refractory period (ERP) is poorly understood after myocardial
      infarction (MI) in vivo. METHODS AND RESULTS: Forty rabbits were randomized into
      either a sham operation (SO) group (n=10) or MI group (n=30), both of which
      underwent thoracotomy, but the left anterior descending coronary artery was
      occluded in the MI group only. The MAPD and ERP of the endocardial, midmyocardial
      and epicardial cells of the infarction zone were observed at baseline, 2 days
      after thoracotomy and then 5 min, 15 min, 30 min, 2 days, 14 days and 60 days
      after coronary occlusion (CO). At baseline, ERP correlated strongly with MAPD90.
      During the 5-30 min after CO, both MAPD90 and ERP of the 3 layers of the
      myocardium shortened markedly (eg, MAPD90 Mid) was approximately 50% of the
      baseline value at 5 min after CO). MAPD90 and ERP recovered gradually over the 2
      60 days after MI. ERPMid exceeded MAPD90 Mid and the post repolarization
      refractoriness phenomenon appeared during the 5-30 min after CO. CONCLUSIONS: The
      different changing trends of the MAPD and ERP of the mid-myocardial cells may
      underlie the arrhythmias that occur after MI.

PMID- 15564709
TI  - Effect of nicorandil, a K+ATP -channel opener, on coronary capillary architecture
      and volume after early myocardial ischemia-reperfusion--a 3-dimensional confocal
      laser microscopic study--.
AB  - BACKGROUND: Previous experimental and clinical studies have reported that
      nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts a
      beneficial effect on microvascular function and clinical outcome after myocardial
      ischemia. The present study assessed whether intravenous administration of
      nicorandil affects the 3-dimensional (3-D) architectural characteristics of
      capillaries and their volume after early myocardial reperfusion. METHODS AND
      RESULTS: Using the hearts of open-chest anesthetized rats, the left anterior
      descending artery was occluded for 7 min followed by reperfusion. Nicorandil or
      saline was infused intravenously during occlusion and reperfusion. The entire
      coronary microvasculature was filled with contrast medium after the hearts were
      arrested. Capillaries were observed 3-dimensionally by confocal laser scanning
      microscopy in both the control area and reperfused area of all samples. The
      capillary volume fraction was computed from the 3-D images. The reperfused area
      in both the nicorandil and saline groups showed characteristic architectural
      changes of the capillaries. Capillary volume fraction in the reperfused area was
      significantly reduced in saline group, compared with nicorandil group [12.7+/
      7.2% vs 18.1 +/-5.3% (p<0.01)]. CONCLUSIONS: Intravenous nicorandil
      administration has a beneficial effect on capillary damage after reperfusion.

PMID- 15564710
TI  - A case of heparin-induced thrombocytopenia with sepsis and congestive heart
      failure--first autopsy report on Japan--.
AB  - An 84-year-old man was referred to the emergency department with severe dyspnea.
      Based on his physical findings, electrocardiogram, X-ray and echocardiographic
      findings, congestive heart failure was suspected and drip infusion of
      prophylactic heparin against intracardiac thrombosis was commenced together with
      dopamine, nitroglycerin and furosemide. Diuresis occurred and the pulmonary
      congestion ameliorated remarkably. Starting on the 20th hospital day, the
      platelet count was gradually reduced (from 256,000 to 55,000 /microl) and the
      fibrin degradation product concentration rose (27.6 microg/ml). However,
      prothrombin time was not prolonged (89%), the concentration of antithrombin III
      was low -normal (69%) and the fibrinogen concentration was high (650 mg/dl).
      Thus, heparin-induced thrombocytopenia (HIT), rather than disseminated
      intravascular coagulation (DIC), was suspected. Heparin was withdrawn on the 24th
      hospital day and replaced by nafamostat mesilate after which the platelet count
      was restored to 100,000 /microl. Enzyme-linked immunosorbent assay for HIT
      antibodies was positive. Unfortunately, the patient died from uncontrolled sepsis
      on the 29th hospital day. At autopsy, platelet-rich thrombi were found in the
      small pulmonary arteries and intestinal arteries. No evidence of DIC, such as
      fibrin-rich thrombosis, was observed. This is the first autopsy report of HIT in
      Japan.

PMID- 15564711
TI  - Left ventricular outflow tract obstruction due to anomalous insertion of
      papillary muscle.
AB  - A 56-year-old man who complained of quadrantic hemianopsia was admitted to
      determine its etiology. Cerebral angiography revealed no organic stenosis.
      Echocardiography showed clear direct continuity between a hypertrophied
      anterolateral papillary muscle and the anterior mitral leaflet, and the left
      ventricular (LV) outflow tract (LVOT) was narrowed by the presence of an
      accessory papillary muscle. The LVOT obstruction caused an intra-LV pressure
      overload that resulted in LV concentric hypertrophy. Arrhythmia, such as
      paroxysmal atrial fibrillation (PAF), was thought to have caused a cerebral
      embolism. Mitral valve replacement (MVR), septal myectomy, and myectomy of the
      abnormal papillary muscle were performed, and complete release of the LVOT
      obstruction was accomplished. Anomalous insertion of papillary muscle is a rare
      cause of LVOT obstruction. Echocardiography was useful in identifying the
      papillary muscle malformation, and surgery was completely curative.

PMID- 15564712
TI  - Plasma concentrations of cytokines and neurohumoral factors in a case of
      fulminant myocarditis successfully treated with intravenous immunoglobulin and
      percutaneous cardiopulmonary support.
AB  - A 53-year-old Japanese man with fulminant myocarditis was referred. Percutaneous
      cardiopulmonary support (PCPS) was introduced immediately and intravenous
      immunoglobulin (IVIG) therapy followed for 2 days. Cardiac function showed signs
      of recovery on the 4th hospital day and the patient was weaned from PCPS on the
      7th hospital day. Creatine kinase-MB peaked at 12 h after admission and was 176
      ng/ml. Endomyocardial biopsy showed active myocarditis. A marked increase of the
      neutralizing antibody titer suggested coxsackievirus B3 infection. Plasma
      concentrations of cytokines and neurohumoral factors were analyzed.
      Proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor
      necrosis factor (TNF-alpha), and anti-inflammatory cytokines, such as IL-1
      receptor antagonist, soluble TNF receptor-1 and IL-10, were elevated on admission
      and all had decreased on the 7th hospital day. Brain natriuretic peptide and
      noradrenaline were already elevated upon admission (1,940 pg/ml and 4.6 ng/ml,
      respectively) and decreased thereafter. Although IVIG therapy under PCPS is a
      common treatment for fulminant myocarditis, the immunological response in vivo
      remains unclear. This case demonstrated suppression of serum cytokines after IVIG
      and PCPS treatment. Immunological parameters in those who have been treated with
      IVIG and PCPS and survived without complications are of great value for
      evaluation of the therapy. Further analysis with more cases in a multicenter
      study is necessary.

PMID- 15564713
TI  - Successful transcatheter coil embolization of coronary artery to left ventricular
      fistula associated with absent pulmonary valve with tricuspid atresia in early
      infancy.
AB  - Transcatheter coil embolization for coronary artery to left ventricular fistula
      was successfully performed in a neonate. At 30 weeks' gestation, fetal
      echocardiography showed a hypoplastic right ventricle with intact ventricular
      septum, absent pulmonary valve, tricuspid atresia, and marked distension of the
      right coronary artery. After birth, the neonate had congestive heart failure and
      the electrocardiogram showed myocardial ischemic changes in the left ventricular
      area. Aortography showed a dilated right coronary artery arising from the
      ascending aorta and draining into the left ventricle. Transcatheter coil
      embolization was carried out on the 9th day after birth. Since the procedure, no
      myocardial ischemic changes have been detected. Transcatheter coil embolization
      is a useful therapy for coronary artery fistula associated with myocardial
      ischemia.

PMID- 15564714
TI  - Production of endothelin-1 and big endothelin-1 by human cardiac myxoma cells-
      implications of the origin of myxomas--.
AB  - BACKGROUND: Although the origin of cardiac myxomas is still controversial, the 2
      main hypotheses are that the tumor cells originate either from multipotential
      mesenchymal cells or from endocardial neural tissue. METHODS AND RESULTS: The
      production of various cytokines in 2 human cardiac myxoma cell lines was examined
      by enzyme-linked immunosorbent assay. After 7 days of culture, extremely high
      concentrations of interleukin-6 were detected in the culture media from both
      myxoma cell lines. Increased production of CXC chemokines, interleukin-8 and
      growth-related oncogene-alpha, were observed in both myxoma cell lines.
      Endothelin (ET)-1 and its precursor, big ET-1, were detected in the culture media
      from both myxoma cell lines. The production of both ET-1 and big ET-1 by myxoma
      cells was higher than by human umbilical vein endothelial cells. Similar to
      endothelial cells, myxoma cells did not produce stem cell factor, granulocyte
      colony-stimulating factor, hepatocyte growth factor, or ET-3. CONCLUSIONS: The
      similarity of the cytokine production pattern between cardiac myxoma cells and
      endothelial cells supports the hypothesis that the tumor cells originate from
      mesenchymal cells capable of endothelial differentiation. Overproduction of CXC
      chemokines may explain, in part, the malignant potential of histologically benign
      myxomas.

PMID- 15564715
TI  - Determinations of B cell fate in immunity and autoimmunity.
AB  - A hallmark of thymus-dependent immunity is the generation of long-lived humoral
      immune responses. The production of long-lived memory B cells (B(mem)) and plasma
      cells (PCs) form the cellular basis for sustaining antibody-mediated immunity.
      During an immune response, the differentiation of B cells to become a B(mem) or
      PC occurs largely at the level of single cell fate decisions. Both of these cell
      populations acquire longevity as a result of antigen-specific, CD40-dependent,
      cognate interactions with helper T cells within germinal centers (GCs). In
      addition to these cellular elements that sustain humoral immunity, a novel GC
      derived B cell that is a precursor to PCs has also been described. This cell is
      long-lived, highly proliferative, and terminally differentiates to end-stage
      cells within the bone marrow, and represents yet another cellular element that
      contributes to the long-lived nature of humoral immunity. Recent studies have
      shown that abnormalities in the B cell compartment of patients and mice with
      antibody-mediated autoimmune disease results from spontaneous GC responses,
      leading to the dysregulation in the development of PCs that produce pathogenic
      autoantibodies with altered homeostasis. The underlying cellular and molecular
      events that drive the loss of self-tolerance remain poorly understood. However,
      newer studies demonstrate that the strength of signaling via the B cell receptor,
      CD40 and BAFF receptors controls B cell fate decisions. Alterations in the
      magnitude of signaling through these molecules likely contribute to immune
      dysregulation that leads to the loss of self-tolerance. Understanding the
      processes of normal PC differentiation will provide strategic insights into
      identifying therapeutic targets for the treatment of antibody-mediated
      autoimmunity.

PMID- 15564716
TI  - Regulatory roles for cytokine-producing B cells in infection and autoimmune
      disease.
AB  - Recent experiments have revealed that B cells can regulate the course of immune
      responses to pathogens and autoantigens by antibody-independent mechanisms. One
      antibody-independent function of B cells is to produce cytokines. In this review
      we describe the identification of IL-10-producing 'regulatory' B cells as well as
      IFNgamma-producing 'effector' Bel cells and IL-4-producing 'effector' Be2 cells.
      We discuss the roles of antigen, pathogen-derived molecules and T cell and
      dendritic cell-derived factors in regulating the differentiation of mature B
      cells into cytokine-producing effector B cells. We also review the recent
      experiments showing that B cell-derived cytokines play pathologic as well as
      protective roles in immune responses to autoantigens, and demonstrate that
      cytokine-producing B cells play unexpectedly complex and potentially opposing
      roles in autoimmune disease.

PMID- 15564717
TI  - The CD19-CD21 signal transduction complex of B lymphocytes regulates the balance
      between health and autoimmune disease: systemic sclerosis as a model system.
AB  - Cell-surface CD19 functions as a general rheostat for defining intrinsic and
      antigen receptor-induced signaling thresholds critical for clonal expansion of
      the B cell pool and humoral immunity. CD19 also governs B cell responses
      initiated through the CD21 receptor, where complement C3d binding to CD21 links
      humoral immune responses with the innate immune system. Alterations in this
      signaling pathway can predispose mice and humans to autoantibody production and
      systemic autoimmunity. Transgenic mice that overexpress CD19 by 20-170% lose
      tolerance and generate autoantibodies. Likewise, B cells from CD21-deficient mice
      overexpress CD19 by approximately 50%, which leads to autoantibody production.
      Autoimmune patients with systemic sclerosis also overexpress CD19 by
      approximately 20%, which may contribute to their intrinsic B cell abnormalities
      and autoantibody production. Thus, chronic B cell activation resulting from
      augmented CD19 expression or signaling through the CD19 pathway may reveal a
      prototype autoimmune disease susceptibility pathway in mice and humans.

PMID- 15564718
TI  - Marginal zone B cell physiology and disease.
AB  - Mature B lymphocytes do not constitute a homogenous pool of cells, and it is now
      clear that several functionally and developmentally distinct subsets exist. Of
      these, marginal zone (MZ) B cells are a subset of peripheral B cells that respond
      vigorously to blood-borne infections, and play a vital role, particularly in host
      survival of infection by encapsulated bacteria. Their fast activation and
      differentiation to antibody-secreting plasma cells allows MZ B cells to bridge
      the gap between innate and adaptive immunity, effected mainly by the more
      prolific follicular B cells. Like other naturally activated lymphocytes, MZ B
      cells may also play a role in homeostasis and tolerance, apart from combating
      infection. Here we will review some of the extracellular signals that affect
      their development, selection and function. We conclude by examining how their
      repertoire, location and interactions with other cell types may be important in
      the induction of autoimmune disease.

PMID- 15564719
TI  - Dendritic cells control B cell growth and differentiation.
AB  - We propose a model where human dendritic cell (DC) subsets control, in a
      coordinated fashion, B cell growth and differentiation. Plasmacytoid DCs drive
      memory B cell differentiation into effector plasma cell via type I interferon and
      IL-6. Type I interferon activates myeloid DCs that regulate B cell priming and
      acquisition of memory phenotype via IL-12, IL-6 and Blys/Baff. This model also
      integrates the role of antigen-specific T cells activated by myeloid DCs. Thus,
      protective humoral immunity results from a highly coordinated interplay of human
      DC subsets. This interplay may explain the spreading of immune response to deal
      with antigenic drift and to maintain an active immunity against mutating microbe.
      It may also provide an explanation for spreading of the autoimmune repertoire as
      autoimmunity develops.

PMID- 15564720
TI  - The biology of CD20 and its potential as a target for mAb therapy.
AB  - CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of
      almost all normal and malignant B cells. It is also the target for rituximab, the
      most effective anti-cancer monoclonal antibody developed to date. Rituximab has
      now been given to over 300,000 lymphoma patients in the last decade and
      interestingly is now being explored for use in other disorders, such as
      autoimmune conditions including rheumatoid arthritis and systemic lupus
      erythematosus. Despite the success in immunotherapy, knowledge about the biology
      of CD20 is still relatively scarce, partly because it has no known natural ligand
      and CD20 knockout mice display an almost normal phenotype. However, interesting
      insight has come from work showing that CD20 is resident in lipid raft domains of
      the plasma membrane where it probably functions as a store-operated calcium
      channel following ligation of the B cell receptor for antigen. In the current
      review, these and data relating to its activity as a therapeutic target will be
      discussed in depth. It is clear that a greater understanding of CD20 biology and
      the effector mechanisms, such as antibody-dependent cellular cytotoxicity,
      complement-dependent cytotoxicity and growth regulation, which operate with anti
      CD20 mAb in vivo will allow more efficient exploitation of CD20 as a therapeutic
      target.

PMID- 15564721
TI  - B lymphocyte depletion in rheumatoid arthritis: targeting of CD20.
AB  - BACKGROUND: During the 1990s evidence emerged to suggest that B lymphocyte
      depletion in rheumatoid arthritis (RA) might be of major benefit. METHODS AND
      RESULTS: In 1997 the B lympholytic monoclonal anti-CD20 antibody rituximab became
      available. Significant clinical efficacy has been demonstrated in RA, initially
      in open studies at University College London and recently in a multicentre
      randomised controlled trial. Forty RA patients at University College London have
      now received in total 75 treatment cycles with rituximab (up to 4 individually)
      alone or in combination with corticosteroid, cyclophosphamide and/or
      methotrexate. Ongoing immunodynamic studies of these patients have shed light on
      a number of questions about both the therapeutic potential of B cell targeting,
      and the pathogenesis of RA. CONCLUSIONS: The effects of B lymphocyte depletion
      lend increasing support to the idea that both the inflammatory effector mechanism
      and the underlying immunoregulatory disturbance in RA are driven by autoantibody
      rather than T cells.

PMID- 15564722
TI  - Treatment of SLE with anti-CD20 monoclonal antibody.
AB  - Systemic lupus erythemaotsus (SLE) is an autoimmune disease involving multiple
      organ systems and characterized by anti-nuclear antibodies. While T cells and
      dendritic cells may play major roles in SLE, several lines of evidence strongly
      suggest a central role for B cells. This article will review the role of B cells
      in human SLE as well as the currently available data on the treatment of SLE by
      depleting B cells with anti-CD20 (rituximab).

PMID- 15564723
TI  - The biochemistry and biology of BAFF, APRIL and their receptors.
AB  - The tumor necrosis factor (TNF) family of related receptors and ligands contains
      a rich collection of molecules that are important players in a broad spectrum of
      biological systems. While several family members are critical for development and
      function of the immune system, providing both activation and death signals, other
      members are involved in nonimmunological functions as diverse as hair follicle
      formation. TNF homology searches during the past several years have led to the
      discovery of numerous novel ligands, two of which will be the focus of this
      review. BAFF, a cytokine responsible for B cell survival, has recently been the
      subject of intense investigation that has expanded our understanding of mature B
      cell genesis, and mechanisms involved in developing B cell pathologies. APRIL is
      a close relative of BAFF and while its biological roles are less well understood,
      it may have both immune and non-immune functions. Herein we will discuss the
      discovery, structure, cognate receptors and functions of these two proteins.

PMID- 15564724
TI  - The BAFF/APRIL system: an important player in systemic rheumatic diseases.
AB  - Many rheumatic diseases have an autoimmune basis, characterized by organ-specific
      inflammation and tissue destruction. Diseases such as rheumatoid arthritis,
      systemic lupus erythematosus or Sjogren's syndrome often associate with abnormal
      B cell function and the production of various autoantibodies. B cell activating
      factor belonging to the TNF family (BAFF) is a B cell survival factor essential
      for B cell maturation, but also contributes to autoimmunity when overexpressed in
      mice. In addition, elevated levels of BAFF have been detected in the serum of
      patients with various rheumatic diseases, suggesting a role for this factor in
      these pathologies. BAFF has additional functions that may be important in
      rheumatic diseases. For instance, excess BAFF leads to the expansion of a subset
      of B cells named marginal zone (MZ) B cells, a cell type able to activate naive T
      cells. In addition, expansion of the MZ B cell population correlates with certain
      autoimmune diseases, and these cells have been detected in inflamed tissues in
      mice and humans. Recently, BAFF was shown to also stimulate T cell activation, an
      aspect that may also contribute to autoimmunity. Finally, BAFF has emerged as a
      potent survival factor for B cell lymphomas and as such may be involved in
      promoting B cell cancers. This result possibly offers an explanation for the
      occasional lymphoma complication observed in a subset of patients with certain
      rheumatic diseases, particularly Sjogren's syndrome. New elements about BAFF
      biology indicate that this factor may be involved in a wider range of pathologies
      than first anticipated, and inhibitors of this factor are likely to provide
      attractive new treatments for rheumatic diseases and B cell lymphomas.

PMID- 15564725
TI  - Human B lymphocyte malignancies: exploitation of BLyS and APRIL and their
      receptors.
AB  - B lymphocyte stimulator (BLyS), also referred to as B cell activating factor of
      the TNF family, is a recently identified tumor necrosis factor (TNF) family
      member shown to be critical for maintenance of normal B cell development and
      homeostasis and it shares significant homology with another TNF superfamily
      member, a proliferation inducing ligand (APRIL). Currently, three receptors have
      been identified that transmit signals upon BLyS and APRIL binding and these
      include B cell maturation antigen, B cell activating factor receptor, and
      transmembrane activator and CAML interactor. The striking effects of BLyS on
      normal B cell maintenance and survival and the largely B lineage-restricted
      pattern of receptor expression, raises the possibility that these TNF family
      ligands and receptors may be involved not only in B cell autoimmunity, but also
      in the pathogenesis and maintenance of mature B lineage hematological
      malignancies. In this article, we will review the spectrum of human B lineage
      malignancies and discuss current evidence supporting a role for BLyS and APRIL in
      fueling the growth and survival of specific B cell malignancies.

PMID- 15564726
TI  - BlySfulness does not equal blissfulness in systemic lupus erythematosus: a
      therapeutic role for BLyS antagonists.
AB  - B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Constitutive
      overexpression of BLyS in mice can lead to systemic lupus erythematosus (SLE)
      like disease. Mice which naturally develop SLE harbor elevated circulating levels
      of BLyS, and treatment of these mice with BLyS antagonists ameliorates disease
      progression and enhances survival. In human SLE, BLyS overexpression is also
      common. Results from a phase-I clinical trial in human SLE with a neutralizing
      anti-BLyS monoclonal antibody have shown the antagonist to be biologically active
      and safe. These features collectively point to BLyS and/or its receptors as
      attractive therapeutic targets in human SLE.

PMID- 15564727
TI  - Five-year trial of deferiprone chelation therapy in thalassaemia major patients.
AB  - Twelve thalassaemia major patients have been given deferiprone 75 mg/kg body
      weight daily as iron chelation therapy for 5 years. Their ages ranged from 18 to
      34 years (mean 24.2) at the end of the study. Two patients were hepatitis C virus
      (HCV) mRNA positive and a further 5 were positive for HCV antibody. The mean
      serum ferritin level fell significantly from 4,302 +/- 2,245 microg/l SD at
      baseline to 3,032 +/- 1,155 microg/l at 2 years (p = 0.037) and 2,229 +/- 1,070
      microg/l (p = 0.007) at 5 years. At the end of the study, liver iron ranged from
      3.59 to 23.7 mg/g dry weight (mean 11.9 +/- 5.4), 3 patients having levels >15
      mg/g. There was no significant change in serum AST levels, but ALT levels fell
      significantly at 2 years (p = 0.019) and 5 years (p = 0.001). Liver biopsy at the
      end of the study showed no evidence of hepatic fibrosis caused by deferiprone.
      Cardiac studies showed no overall change in left ventricular ejection fraction
      but a significant improvement in isovolumic relaxation time (p = 0.045). We
      conclude that in this albeit small group of thalassaemia major patients,
      deferiprone was a safe long-term method of iron chelation. In a minority, higher
      doses of deferiprone or a combination with desferrioxamine would be needed to
      lower liver iron below 15 mg/g.

PMID- 15564728
TI  - Cyclosporin A-associated changes in red blood cell membrane composition,
      deformability, blood and plasma viscosity in rats.
AB  - Most of the studies concerning the effects of cyclosporin A (Cs A) on red blood
      cell (RBC) rheology were carried out in human transplant recipients who may still
      have residual insufficiency and concomitant administration of other
      immunosuppressive and antihypertensive drugs. The aim of this study is to
      evaluate the effects of Cs A on red cell rheology and membrane composition in
      nontransplant healthy rats. Female Wistar albino rats were divided into two
      groups of 10 animals each. Rats received 10 mg/kg Cs A, i.p. or saline for 4
      weeks. Cs A administration significantly increased the RBC deformability, and
      plasma and blood viscosity (p < 0.001, p < 0.01 and p < 0.01, respectively). Cs A
      administration to the rats increased RBC membrane cholesterol (CHO) levels and
      the CHO/phospholipid (PL) ratio significantly (p < 0.01 and p < 0.05,
      respectively) but did not change RBC membrane proteins and membrane PL levels.
      These results suggest that Cs A changes the rheological functions of RBC and
      lipid content of RBC membrane in healthy rats and thereby it may play an
      important role in the regulation of microcirculation.

PMID- 15564729
TI  - The prevalence of hepatitis C and hepatitis G virus infection in patients with B
      cell non-Hodgkin lymphomas in Greece: a Hellenic Cooperative Oncology Group
      Study.
AB  - Our aim was to investigate the association between chronic hepatitis C virus
      (HCV) infection and B cell non-Hodgkin lymphoma (NHL) in the Greek population. We
      studied 120 patients (70 men and 50 women, mean age 59 years) diagnosed with NHL.
      One hundred and eight had B cell NHL (90%) and 12 had T cell NHL (10%). The
      presence of anti-HCV antibodies in patients and controls was investigated using
      the monoclonal enzymatic immunoassay (MEIA) method. The detection of HCV RNA and
      hepatitis G virus (HGV) RNA in patients with B cell NHL and anti-HCV-positive
      controls was performed using an RT-PCR technique. Anti-HCV antibodies were
      present in only 2 of the 108 patients with B cell NHL (1.9%), while the
      prevalence of HCV infection in the healthy population was 0.6%, and in patients
      with various solid tumors treated with chemotherapy, it was 0.99%. Ten of the 108
      B cell NHL patients (9.26%) were diagnosed as HGV RNA positive, while the
      prevalence of HGV infection in 285 Greek blood donors was 0.7%. Our findings do
      not confirm a strong association between HCV infection and B cell NHL for Greek
      patients. The increased prevalence of HGV infection detected in patients with NHL
      could imply the potential participation of HGV in the pathogenesis of NHL.

PMID- 15564730
TI  - Mediastinal bulky tumour in Hodgkin's disease and prognostic value of positron
      emission tomography in the evaluation of post-treatment residual masses.
AB  - Among the 193 patients (82 female, 111 male) treated primarily for Hodgkin's
      disease at our clinic between 1990 and 2001 and followed up until 2003, 42 (22%)
      had mediastinal bulky tumours (MBTs) by the Cotswolds criteria. The rate of MBT
      diagnosis was significantly greater in the early stage of the disease, these
      patients were younger and--in contrast to the other group--they all received
      combined therapy. No significant differences were found in the overall and
      relapse-free survival rate in the two groups, but relapse and death rates were
      lower in the patients with bulky tumours. Of the total number of patients, 27
      underwent a total of 31 18F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) examinations, mainly for the evaluation of post-treatment residual mass
      viability. In the 12 positive cases, the majority of patients received further
      therapy. During the mean follow-up time of 58 months (range 5-98 months) after
      obtaining negative results, progression of the disease was found in 2 cases 14
      and 23 months later, respectively. Based on our results, we conclude that FDG-PET
      examinations show a good correlation with clinical follow-up results.

PMID- 15564731
TI  - Performing bone marrow harvest on an outpatient basis: a single center UK
      experience.
AB  - Bone marrow harvest (BMH) has historically been performed on an inpatient basis
      with a minimum of overnight inpatient stays. We commenced a program of outpatient
      (day case) BMH in 1999, performing 54 day case BMHs over a 3-year period. Of the
      total of 54 cases, 51 were known patients with hematological malignancies and 3
      were healthy normal donors. Seven were excluded from day case BMH. Five (10.6%)
      of 47 patients/donors who were accepted for day case BMH required overnight
      admission. Two developed hypotension requiring intravenous fluid resuscitation.
      Two had excessive vomiting and 1 a difficult and prolonged harvest and was
      admitted at the request of the anesthetist. None of the patients admitted
      required more than overnight admission and 42 (89.4%) were discharged the same
      evening. In conclusion, day case BMH is safe, cost-effective, and reduces the
      pressure on inpatient beds.

PMID- 15564732
TI  - Primary salivary gland lymphoma: a clinicopathologic study of 23 cases in Taiwan.
AB  - Twenty-three patients with primary salivary gland lymphoma were diagnosed between
      1990 and 2001. The sites of involvement were the parotid gland in 13, the
      submandibular gland in 9 and the minor salivary gland in 1. The sites of lymphoma
      involvement beyond the salivary glands were the cervical lymph nodes in 7, bone
      marrow in 3, the axillary lymph nodes in 3, the nasopharynx in 2, the abdominal
      lymph nodes in 2, the palate, the subconjunctiva, and the spleen in 1 each
      patient. Histologically, 19 patients had lymphomas of mucosa-associated lymphoid
      tissue (MALT) with myoepithelial sialadenitis in 13, 3 patients had diffuse large
      cell lymphomas and 1 had follicular lymphoma. Six patients were in stage I, 4 in
      II, 1 in III and 12 in IV. Eight of 23 patients (35%) had autoimmune diseases
      before or after the diagnosis of NHL and all suffered from MALT lymphoma. Four
      patients with parotid MALT lymphoma had primary or secondary Sjogren's syndrome.
      One each patient suffered from hyperthyroidism, systemic lupus erythematosus,
      membranoproliferative glomerulonephritis and cryoglobulinemia, respectively. All
      the 6 stage I patients had achieved complete remission (CR) without relapses 17
      84 months (median 44 months) after treatment. Excluding a stage IV patient with
      follicular lymphoma who died at 3.5 months without treatment, CR was achieved in
      all of the remaining 16 patients. However, a high relapse rate (9/16, 56%) was
      noted in stage II-IV patients. These patients tended to relapse in the original
      sites, but achieved CR again after chemotherapy or radiotherapy. One patient with
      MALT lymphoma developed histologic transformation into diffuse large lymphoma
      during relapse and died of refractory disease. Overall, only 2 patients
      succumbed. The overall survival and relapse-free survival rates at 5 years were
      94.7 and 51.4%, respectively. Thus, salivary gland lymphoma proved to be an
      indolent disease.

PMID- 15564733
TI  - Transient severe eosinophilia precipitating massive venous thrombosis in a
      patient with hereditary thrombophilia.
AB  - We describe a patient homozygous for both the prothrombin G20210A and
      methylenetetrahydrofolate reductase C667T mutations who was symptom-free for 40
      years and developed near-catastrophic thrombotic complications following
      transient, severe eosinophilia. This course of events raises the possibility of
      an increased risk of thrombosis associated with transient eosinophilia in the
      presence of hereditary thrombophilia and supports the concept of multifactorial
      etiology of venous thrombosis. Our experience suggests that in patients with
      severe eosinophilia, evaluation for known causes of hereditary or acquired
      thrombophilia may be useful for identifying subjects at increased risk of
      thrombosis.

PMID- 15564734
TI  - Very late central nervous system relapse in a patient with B cell lymphoblastic
      lymphoma.
AB  - Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case
      of a patient who developed central nervous system (CNS) relapse of LBL 16 years
      after the onset of the primary disease. An 8-year-old girl was hospitalized with
      a skin tumor in the occipital region on November 27, 1984. Examination of a
      biopsy of the skin tumor showed typical features of non-Hodgkin's lymphoma
      (diffuse medium-sized cell type). She received multiagent chemotherapy and went
      into remission. On July 4, 2000, she was hospitalized with persistent headache.
      Cranial magnetic resonance imaging showed a cerebellar lesion, which was
      hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted
      images. A midline suboccipital craniotomy was performed and pathological
      examination revealed a diffuse proliferation of lymphoid cells, which were
      positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3
      and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised
      immunohistochemistry of the primary specimens of skin tumor obtained 16 years
      earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain
      reaction products for the immunoglobulin gene from both the skin and cerebellar
      specimens were an identical size. Thus, the original diagnosis of diffuse medium
      sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was
      apparent in the present case. After salvage chemotherapy, the patient underwent
      high-dose chemotherapy with autologous peripheral blood stem cell support and
      subsequent craniospinal irradiation. She went into a lasting complete remission.

PMID- 15564735
TI  - Severe autoimmune thrombocytopenic purpura during interferon-alpha therapy for
      chronic myelogenous leukemia.
AB  - Interferon (IFN)-alpha is a leukocyte-derived cytokine and is used to treat
      several hematopoietic malignancies. The most common adverse effects of IFN-alpha
      are flu-like symptoms and usually insignificant. However, adverse effects due to
      autoimmune mechanisms are often hazardous and irreversible, although their
      frequency is low. In the present report, we describe a 55-year-old female with
      chronic myelogenous leukemia who developed severe autoimmune thrombocytopenia
      during IFN-alpha therapy. The lowest platelet count was 6 x 10(9)/l with severe
      hemorrhagic tendency. The present report strongly suggests the clinical
      importance of autoimmune thrombocytopenia as an adverse effect of IFN-alpha.

PMID- 15564736
TI  - Characteristics of HFE C282Y homozygotes younger than age 30 years.

PMID- 15564737
TI  - Cerebrospinal fluid excitatory amino acids and tau protein in children with acute
      lymphoblastic leukemia treated according to the BFM protocol.

PMID- 15564738
TI  - Long-term molecular remission after nonmyeloablative stem cell transplantation in
      a patient with chronic myelogenous leukemia in the chronic phase.

PMID- 15564739
TI  - Prevalence of factor V leiden, factor V cambridge, factor II G20210A and
      methylenetetrahydrofolate reductase C677T mutations in healthy and thrombophilic
      Serbian populations.

PMID- 15564740
TI  - Growth kinetics of human mesenchymal stem cells from bone marrow and umbilical
      cord blood.

PMID- 15564741
TI  - Genetic diversity of hepatitis B virus strains derived worldwide: genotypes,
      subgenotypes, and HBsAg subtypes.
AB  - Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were
      used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the
      described two subgenotypes each for A and F, also B, C, and D divided into four
      subgenotypes each in the analysis of complete genomes supported by significant
      bootstrap values. The subgenotypes of B and C differed in their geographical
      distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined
      to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1.
      Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East
      Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-,
      and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern
      of defined geographical distribution was less evident for D1-D4, where the
      subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to
      their divergence having occurred a longer time ago than for genotypes B and C,
      with D4 being the first split and still the dominating subgenotype of D in the
      Oceania. The genetic diversity of HBV and the geographical distribution of its
      subgenotypes provide a tool to reconstruct the evolutionary history of HBV and
      may help to complement genetic data in the understanding of the evolution and
      past migrations of man.

PMID- 15564742
TI  - Evaluation of three molecular biology-based assays for the detection of GB virus
      C/hepatitis G virus in clinical specimens.
AB  - OBJECTIVE: The present study was performed to evaluate the reliability of three
      reverse transcription-polymerase chain reaction (RT-PCR) assays, one commercial
      and two 'homebrew', for GB virus C (GBV-C)/hepatitis G virus (HGV) RNA detection
      in clinical specimens. We, therefore, investigated the virus prevalence with the
      method that gave us the best performances. METHODS: The commercial assay
      amplified sequences from the viral 5'-untranslated region (5'UTR) and non
      structural 3 (NS3) region. The non-commercial assays 1 and 2 were based on
      different primers for the 5'UTR consensus sequence. RESULTS: The percentage of
      overall concordance by the three methods was 91.7%, raising to 93.0% when only
      the two non-commercial methods were compared. Assay 1 showed low sensitivity
      (57.1% vs. the commercial assay, 58.8% vs. assay 2), with 100% specificity. The
      commercial assay gave 18 of 54 (33.3%) 'false-negative' results, concordantly
      negative by the other assays. The prevalence of GBV-C/HGV RNA among the HIV+
      patients was 27.0 and 32.6% in HIV/HCV co-infected patients. CONCLUSION: These
      data suggest that assay 2 has higher reliability as compared to the other two
      methods and may be used for an accurate GBV-C/HGV RNA detection in clinical and
      epidemiological studies.

PMID- 15564743
TI  - Intracellular expression patterns of the human papillomavirus type 59 E1/E4
      protein in COS cells, keratinocytes, and genital epithelium.
AB  - OBJECTIVE: To compare and contrast the intracellular distribution pattern of the
      human papillomavirus type 59 (HPV 59) E1/E4 protein in COS cells, human
      keratinocytes, and naturally infected genital epithelium. METHODS: The HPV 59
      E1/E4 protein was expressed in COS cells and NIKS cells (immortalized human
      keratinocytes). A subset of NIKS cells was induced to differentiate. The
      intracellular distribution pattern of E1/E4 and the effects of E1/E4 expression
      on the cytoskeleton network were compared for COS and NIKS cells. Expression of
      E1/E4 was examined in HPV 59-infected foreskin xenografts grown in athymic mice
      and in a natural HPV 59-infected genital lesion. RESULTS: The HPV 59 E1/E4
      protein formed dense perinuclear inclusions in COS cells, similar to those
      reported for the HPV 16 E1/E4 protein. In contrast, the E1/E4 protein was
      diffusely cytoplasmic in undifferentiated NIKS cells, co-localizing with an
      intact cytokeratin filament network. The E1/E4 protein was concentrated in the
      region of the cornified cell envelope (CCE) of differentiated NIKS cells, co
      localizing with involucrin, a CCE component. A similar distribution in the region
      of the CCE was observed for E1/E4 protein in HPV 59-infected human epithelial
      tissues. CONCLUSIONS: The HPV 59 E1/E4 protein is cytoplasmic and co-localizes
      with an intact cytokeratin filament network in undifferentiated keratinocytes.
      The E1/E4 protein is distributed in the region of the CCE and co-localizes with
      involucrin in differentiated human keratinocytes, consistent with the
      intracellular distribution pattern observed in HPV 59-infected epithelium.

PMID- 15564744
TI  - High sustained virologic response rate after interferon monotherapy in Japanese
      hepatitis C patients with a low HCV RNA titer and/or HCV genotype 2. A
      prospective study.
AB  - OBJECTIVE: Hepatitis C virus (HCV) RNA titer and HCV genotype are considered to
      be major determinants of the outcome of interferon monotherapy. To clarify
      whether interferon monotherapy is really effective in patients with the
      appropriate viral parameters, we prospectively examined these parameters and
      treated the patients with interferon monotherapy. METHODS: Sixty-four patients
      with an HCV RNA titer <100 kIU/ml and/or HCV genotype 2 were enrolled in the
      study. Eighteen patients with an HCV RNA titer >100 kIU/ml and genotype 1 were
      also enrolled as controls. All patients were treated with 10 megaunits of
      interferon-alpha2b every day for 2 weeks and then 3 times a week for 24 weeks.
      RESULTS: Of the 64 patients with either HCV RNA <100 kIU/ml and/or genotype 2,
      seven dropped out from the study. Of the remaining 57 who completed the
      treatment, 48 (84%) showed a virologic sustained response. In contrast, only 4 of
      the 18 patients (22%) with HCV RNA >100 kIU/ml and genotype 1 were virologic
      sustained responders (p < 0.001). CONCLUSION: Our current study showed that the
      patients with HCV RNA <100 kIU/ml and/or HCV genotype 2 are good candidates for
      interferon monotherapy.

PMID- 15564745
TI  - Benefit of lamivudine therapy and factors associated with clinical outcome in
      spontaneous severe acute exacerbation of chronic hepatitis B virus infection.
AB  - OBJECTIVE: During the course of chronic hepatitis B virus (HBV) infection, severe
      acute exacerbations of the infection often occur spontaneously and follow a
      fulminating progression to fatal hepatic failure. The aim of this study was to
      clarify potential factors, including benefit of lamivudine therapy, which could
      influence clinical course of the serious disease in an area of intermediate HBV
      endemicity. METHODS AND RESULTS: Using a database of 3,163 chronically HBV
      infected patients, 418 (13.2%) developed acute exacerbation of hepatitis B. Of
      the 418 patients, 52 (12.4%) spontaneously developed severe acute exacerbation
      and were included in this study. Of the 52 patients, 23 were treated with
      lamivudine. In multivariate analyses, fulminating progression to hepatic failure
      (odds ratio, 15.45; 95% confidence interval, 3.71-64.41; p = 0.0002) was a
      significantly independent predictor of patient survival. Three variables were
      independently associated with fulminating development of hepatic failure:
      presence of cirrhosis (29.06, 1.74-85.56, 0.019, respectively), higher baseline
      bilirubin level (14.89, 1.31-52.91, 0.029, respectively), and genotype B (22.14,
      1.59-29.68, 0.021, respectively). Treatment lacking lamivudine was a significant
      factor that contributed to shorter survival time, development of hepatic failure,
      and progression to cirrhosis in univariate analyses (p = 0.014, 0.012 and 0.0030,
      respectively). CONCLUSION: In an area of intermediate HBV endemicity, certain
      proportion of chronic hepatitis B patients could spontaneously develop the
      serious disease. Factors influencing clinical course of the disease should be
      identified to improve prognosis and establish more rational and effective
      therapeutic strategies. Lamivudine therapy could potentially benefit the serious
      disease, although larger series of patients and longer follow-up periods are
      needed.

PMID- 15564746
TI  - Specific in vitro interaction between papillomavirus E2 proteins and TBP
      associated factors.
AB  - The bovine and human papillomavirus (BPV/HPV) E2 proteins bind specifically to
      palindromic sequences ACCGN4CGGT that are concentrated within the viral long
      control region, where they regulate viral oncogene transcription. E2 can activate
      viral promoters over relatively large distances within the viral genome and was
      shown to cooperate with a number of cellular transcription factors.
      Transcriptional activator proteins, such as E2, are thought to act, at least in
      part, by influencing the assembly and/or stability of preinitiation complexes and
      it has been suggested that the transcription factor IID, composed by the TATA
      binding protein (TBP) and numerous TBP-associated factors (TAFs), is a possible
      target of this important viral protein. In this paper, we demonstrate that E2
      proteins associate in vitro with several TAFs, in particular with TAFII250 and
      TAFII80. In addition, we observed that the association of TAFII250 with BPV1 E2
      is stronger than with HPV18 E2 and that the carboxy terminal domain of both viral
      proteins is involved in this interaction. On the other hand, TAFII80 binds with
      similar strength to both E2 proteins through their amino terminal region. These
      observations may help to explain the different behavior of bovine and human E2
      proteins, since BPV E2 is a stronger transcriptional activator than HPV18 E2.

PMID- 15564747
TI  - Modifications in SENV DNA detection and/or SENV subtype determination over a
      prospective follow-up in a cohort of HIV-positive patients: is this a moving
      target?
AB  - SEN virus (SENV) is a new family of single-stranded DNA viruses with eight
      different strains, A-H. The modifications in SENV DNA detection and subtype
      distribution were studied over a long-term follow-up (48 +/- 32.5 months) in 52
      HIV-infected patients. 46% of the patients in the first sample and 34.6% in the
      second sample were found to have detectable SENV viremia. While the most
      prevalent variant in the first sample was found to be genotype A (83.3%), the
      second sample revealed a broader subtype diversification. Several epidemiological
      and clinical variables were tested in univariate model for clearance of
      detectable SENV viremia, but none of them reached statistical significance. In
      conclusion, a high degree of instability of both SENV DNA detection and subtype
      distribution in a cohort of HIV-infected patients was suggested, which may have
      important implications for further studies on both SENV epidemiology and its
      clinical impact.

PMID- 15564748
TI  - Interferon therapy for 2 years or longer reduces the incidence of
      hepatocarcinogenesis in patients with chronic hepatitis C viral infection.
AB  - OBJECTIVE: The purpose of this clinical study was to determine the effect of long
      term interferon (IFN) administration on the incidence of hepatocellular
      carcinomas (HCC) in chronic hepatitis C patients, without eradication of
      hepatitis C virus (HCV) by IFN therapy. METHODS: The number of patients with
      biopsy-proven chronic hepatitis with moderate or severe staging, HCV genotype 1b,
      a high viral load exceeding 1 MEq/ml (mega equivalents per milliliter), who
      received 6 MU of natural IFN-alpha daily for 2-8 weeks, followed by three
      times/week for 16-22 weeks, as initial IFN therapy, and positivity for HCV RNA
      during IFN administration was 131. 47 of the 131 patients continued to be treated
      with IFN (long-term IFN group, dose 3 or 6 MU twice or three times weekly for 1.5
      10.5 years, median 4.0 years) after initial IFN therapy, while 84 patients did
      not receive any IFN therapy apart from the initial 6-month course (no-add-IFN
      group). The patients were prospectively monitored, and the cumulative incidence
      of HCC and risk factors for HCC were examined. RESULTS: The 5- and 10-year
      cumulative rates of HCC were 1.9 and 6.4% and 1.9 and 26.8% for long-term IFN and
      no-add-IFN groups, respectively. Cox regression analysis indicated that the
      relative risk of HCC in the patients of the no-add-IFN group was 8.72 times of
      that in patients of the long-term IFN group. CONCLUSION: Long-term IFN therapy in
      patients with chronic HCV infection is effective in preventing
      hepatocarcinogenesis.

PMID- 15564749
TI  - Adefovir dipivoxil for treatment of breakthrough hepatitis caused by lamivudine
      resistant mutants of hepatitis B virus.
AB  - OBJECTIVE: Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild
      type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in
      vivo. The aim of this study was to evaluate the efficacy of ADV against
      lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to
      lamivudine for patients with severe acute exacerbation of hepatitis caused by
      lamivudine-resistant mutants. METHODS: Fourteen patients with breakthrough
      hepatitis were treated with ADV. Four of the 14 patients also received IFN as
      combined treatment for severe acute exacerbation of hepatitis. RESULTS: At week
      24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log
      copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group
      compared to baseline. The median decrease in alanine aminotransferase (ALT)
      levels from baseline to week 24 was -1.05 times the upper limit of normal (ULN)
      in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and 
      22.3 times the ULN in the ADV + IFN group. CONCLUSIONS: Administration of ADV add
      on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT
      levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients
      with severe acute exacerbation of hepatitis.

PMID- 15564750
TI  - Virus Overlay Protein Binding Assay (VOPBA) reveals serotype specific
      heterogeneity of dengue virus binding proteins on HepG2 human liver cells.
AB  - OBJECTIVE: This study sought to investigate the presence of dengue virus binding
      proteins expressed on the surface of HepG2 cells and to determine if there were
      serotype specific differences in binding. METHODS: HepG2 cell membrane proteins
      were extracted and separated by SDS-PAGE, transferred to nitrocellulose membranes
      and incubated with dengue virus serotypes 2, 3 and 4 under varying hybridization
      conditions. The positions of dengue virus binding proteins were established with
      a pan-specific anti-dengue virus monoclonal antibody. RESULTS: Dengue virus
      binding proteins were seen at approximately 78-80, 90, 98, and 102 kD for dengue
      serotype 2, 90, 130 and 182 kD for dengue serotype 3, and 90 and 130 kD for
      dengue serotype 4. Binding of the serotypes 3 and 4 was significantly altered by
      the hybridization conditions, while serotype 2 was affected to a lesser extent.
      CONCLUSIONS: The virus overlay assay used here provides further evidence that
      there is a serotype specific component regulating the entry of the dengue virus
      into cells. Given that several virus binding proteins are seen for each serotype,
      multiple proteins may be required to facilitate the entry of the virus into some
      cell types.

PMID- 15564751
TI  - Prevalence of hepatitis B and hepatitis C viral infections in Indian patients
      with chronic renal failure.
AB  - The present study reports prevalence of posttransplant hepatitis B virus (HBV)
      and hepatitis C virus (HCV) infection in 256 patients with chronic renal failure
      (CRF) and with a history of either renal transplant or hemodialysis. Out of 256
      patients 138 had renal transplant and 118 were on maintenance hemodialysis. Among
      the patients screened, 7% had HBV infection alone, 46% were infected with HCV
      alone, while 37.10% were found to have co-infection of both the viruses. Our
      findings implicate these viruses as the major cause of posttransplant hepatitis
      in Indian patients with CRF and indicate implementation of stringent screening
      procedures for these two viral infections.

PMID- 15564752
TI  - Immunomodulatory therapy in ophthalmology - is there a place for topical
      application?
AB  - Topical corticosteroids, although effective in the treatment of ocular immune
      mediated diseases, are well known for their ocular side-effects. Not
      surprisingly, a variety of alternative immunomodulatory agents have been tested
      for topical use including cyclosporin A (CsA), mycophenolate mofetil (MMF),
      tacrolimus (FK506), rapamycin (sirolimus) and leflunomide. Local application
      bears the possibility to avoid the severe side-effects of systemic therapy. The
      effect of topical therapy is naturally restricted to local immune response
      mechanisms, such as antigen presentation by Langerhans and dendritic cells.
      Moreover, many immunomodulatory agents (e.g. CsA) are lipophilic and thus have
      low water solubility and penetrate insufficiently intra-ocularly, often being
      stored in the lipophilic corneal epithelial barrier. Therefore, the therapeutical
      success is limited for intra-ocular immune-mediated diseases like anterior
      uveitis. However, a multitude of strategies have been introduced to circumvent
      these problems including complexing substances such as cyclodextrins (CDs) and
      liposomes. In the prevention and treatment of transplant rejection after
      keratoplasty, many attempts to introduce topical immunomodulatory therapy have
      failed; on the other hand, further therapeutic options not primarily expected are
      being evaluated today such as treatment of severe keratoconjunctivitis sicca. In
      our own studies, we investigated the pharmacokinetics of topical treatment with
      different agents including MMF and evaluated the efficacy of topical treatment in
      animal models for uveitis and keratoplasty. Taken together, topical
      immunomodulatory therapy will not replace systemic therapy but further treatment
      options can be expected.

PMID- 15564753
TI  - Krypton laser membranotomy for premacular hemorrhage.
AB  - BACKGROUND: To evaluate the safety and effectiveness of krypton laser
      membranotomy. METHODS: Eleven patients (12 eyes) with premacular hemorrhage were
      enrolled from April 1998 to November 2002. The causes of premacular hemorrhage
      were proliferative diabetic retinopathy (7 patients, 8 eyes), Valsalva
      retinopathy (3 patients) and leukemia (1 eye). Krypton laser was used to create a
      membranotomy on the sloping edge of the premacular hemorrhage. Five eyes with
      proliferative diabetic retinopathy were treated with inferior panretinal
      photocoagulation and laser membranotomy simultaneously. After intravitreal
      dispersion of premacular blood, fundus examinations were performed in all eyes
      and fluorescein angiography in 5 patients to evaluate the retinal damage.
      RESULTS: Vision was improved within 2 weeks after surgery in all eyes with
      premacular hemorrhage, which received krypton laser membranotomy. No retinal
      damage was seen at the site of membranotomy. No eye needed vitrectomy
      postoperatively during the follow-up (mean, 17 months). CONCLUSION: Krypton laser
      membranotomy appears to be a safe and simple alternative procedure for treating
      selected cases of premacular hemorrhage. Further trials are necessary to evaluate
      its benefit.

PMID- 15564754
TI  - Treatment options in the management of choroidal metastases.
AB  - We performed a retrospective study of 40 consecutive patients (50 eyes) treated
      for choroidal metastases of solid systemic malignancies in order to evaluate
      treatment results. Patients received either systemic or local therapy or a
      combination of both. The most common primary tumor was breast carcinoma (62.5%).
      Systemic chemotherapy alone was used in 13.3% of eyes, local therapy alone in
      44.4%, and a combination of both in 42.2% of eyes. Local treatment modalities
      included brachytherapy, external beam irradiation, and laser photocoagulation.
      Complete regression of the choroidal metastases was seen in 57.8% of eyes,
      partial regression in 15.6 and no response in 4.4%; 22.2% were not available for
      re-evaluation. We have concluded that the treatment modality in patients with
      metastatic ocular disease should be individually tailored. When ocular metastases
      are concurrent with widespread metastatic disease, systemic chemotherapy alone or
      in combination with local therapy is reasonable. In patients manifesting
      metastases in the eyes alone, local therapy modalities may be safe, allowing
      conservation of visual functions with minimal systemic morbidity.

PMID- 15564755
TI  - Improvement of visual acuity in eyes with diabetic macular edema after treatment
      with pars plana vitrectomy.
AB  - BACKGROUND: Diabetic macular edema (DME) is the leading cause of severe visual
      loss in patients with diabetic retinopathy. This is so despite the fact that
      argon laser photocoagulation of the macula (M-ALC) has been shown to be
      beneficial. Recently, it has been suggested that pars plana vitrectomy (PPV) can
      lead to the resolution of DME and stop the deterioration of central visual
      acuity. PURPOSE: To explore the potential benefit of PPV for the treatment of
      DME. PATIENTS AND METHODS: PPV was carried out in 30 eyes of 21 consecutive
      patients (median age 71 years, range 61-88 years) with type II diabetes mellitus
      suffering from DME. 23 eyes had non-proliferative diabetic retinopathy (NPDR) and
      7 eyes had proliferative diabetic retinopathy (PDR) in addition to DME. Posterior
      vitreous detachment had to be carried out in all cases. If epiretinal membranes
      were present (23 eyes), they were removed. In 13 eyes (initially 11 eyes) the
      internal limiting membrane (ILM) was also removed. Prior to PPV 8 eyes had
      received M-ALC. Three eyes had M-ALC after PPV. One eye developed a retinal
      detachment 6 weeks after PPV and was excluded form the analysis. After an initial
      treatment failure two eyes underwent repeat PPV with peeling of the ILM. Both
      eyes of another patient had 2 repeat PPVs because of recurrent vitreous
      hemorrhage. Median follow-up was 16 months (range 1-62 months). RESULTS:
      Following PPV the macula flattened or became attached in 20/27 (74%) eyes. 15/18
      (83%) eyes showed reduction or disappearance of leakage during fluorescein
      angiography. Central visual acuity increased by two to six lines in 15/27 (56%)
      for the whole group at 6 months after PPV. For the subgroup (18 eyes) for which
      the evolution of visual acuity prior to PPV could be documented mean and median
      visual acuity had decreased markedly from 0.26 +/- 0.19 resp. 0.2 (range 0.03
      0.6) to 0.12 +/- 0.09 resp. 0.1 (range 0.02-0.4) during the 12 months preceding
      PPV and increased to 0.28 +/- 0.23 resp. 0.2 (range 0.03-0.8) during the 12
      months following PPV. CONCLUSION: PPV almost always results in a reduction and
      often complete disappearance of DME as evidenced by ophthalmoscopy and
      fluorescein-angiography. Most importantly, central visual acuity often increases,
      sometimes to a very large extent with dramatic improvement in quality of life of
      the patients.

PMID- 15564756
TI  - Cytotoxicity evaluation of soft contact lens care solutions on human conjunctival
      fibroblasts.
AB  - PURPOSE: To determine whether different contact lens care solutions for soft
      lenses cause damage to human conjunctival cells. METHODS: Primary cultured human
      conjunctival fibroblasts were incubated with various concentrations of four
      different commercially available soft contact lens care solutions (OptiFree,
      Renu, SoloCare, Titmus) at concentrations of 5, 10 and 50 microl/ml medium.
      Toxicity was examined by determination of (1) the cell viability and
      mitochondrial activity with the colorimetric MTT test, and (2) the number of
      living cells with a cell analysis system (CASY 1) as compared with untreated
      cells. RESULTS: For all four soft contact lens care solutions at a concentration
      of 5 mul/ml medium, no significant decrease in mitochondrial activity of the
      human conjunctival fibroblasts was found by the MTT test. At 10 microl/ml, only
      OptiFree and Titmus reduced mitochondrial viability significantly. The greatest
      reduction in mitochondrial activity occurred with all of the four soft contact
      lens care solutions at a concentration of 50 microl/ml. No significant decrease
      in the number of living conjunctival fibroblasts was observed by CASY 1 even at
      higher concentrations of the four solutions investigated. CONCLUSION: This in
      vitro study demonstrates that the examined soft contact lens care solutions
      induce changes in mitochondria of human conjunctival cells only at higher doses
      as observed by the MTT test. However, this damage to the mitochondria did not
      lead to cell death as shown by the cell analysis system.

PMID- 15564757
TI  - Retinal peripapillary blood flow before and after topical brinzolamide.
AB  - PURPOSE: To study the effect of topical brinzolamide on retinal capillary blood
      flow by the Heidelberg Retina Flowmeter (HRF) in patients with glaucoma. METHODS:
      Twenty patients with glaucoma were consecutively recruited. One eye for each
      patient was randomly selected. Patients were classified as glaucomatous if they
      had an abnormal visual field and/or an abnormal optic nerve head with an
      intraocular pressure (IOP) greater than 21 mm Hg without any treatment. After an
      eye examination, baseline retinal blood flow measurements were made with confocal
      scanning laser Doppler flowmetry. Blood flow and IOP measurements were then
      repeated after 1 month of treatment. Blood flow measurements were analyzed by
      using an automatic full-field perfusion image analysis (AFFPIA) program. The
      blood flow was calculated in the superior and inferior part of the optic disk. In
      each area, the blood flow was calculated as temporal area, the nasal area and the
      rim area as for software AFFPIA. RESULTS: The mean age of the patients was 56 +/-
      7 (mean +/- standard deviation) years. The mean IOP before treatment was 23.7 +/-
      1.5 mm Hg while the mean IOP after 4 weeks of treatment was 19.1 +/- 2.2 mm Hg.
      This difference was statistically significant (p < 0.01). Significant (p < 0.05)
      increases in retinal blood flow were found for the temporal and nasal areas
      between baseline and 1 month after the treatment. No difference was found between
      superior and inferior sectors. CONCLUSION: Topical brinzolamide reduced the IOP
      significantly and apparently improved retinal blood flow as measured by the HRF.

PMID- 15564758
TI  - Visual acuity in premature infants.
AB  - PURPOSE: To measure grating visual acuity in premature infants and compare it
      with that in full-term infants. METHODS: The visual acuity of 73 premature and 73
      full-term infants was tested at 6 months of age by the Teller Acuity Card
      procedure. All premature infants had undergone indirect funduscopy for the
      detection of retinopathy of prematurity (ROP). Seven infants had developed ROP.
      The mean gestational age of the premature infants was 33 +/- 1.4 weeks as
      compared with 39.9 +/- 0.9 weeks in the full-term infants. The mean birth weights
      of the 2 groups were 1,906 +/- 412 and 3,244 +/- 420 g, respectively. RESULTS:
      Impaired binocular visual acuity was found in 53.4% of the premature infants, but
      in only 11% of the full-term infants (p < 0.0001). Impaired monocular visual
      acuity was found in 13.7% of the premature infants as compared with 2.7% of the
      full-term infants. Within the premature infant group, monocular visual acuity was
      impaired in 42.9% of those with ROP and in 10.6% of those without ROP (p =
      0.0497). Pathological refraction was found in 33.3% of the prematures without ROP
      and in 14.3% of the prematures with ROP. This difference was not statistically
      significant. Visual acuity of preterm infants was not different from full-term
      infants when examined at 6 months of postconceptual age. CONCLUSIONS: Both
      monocular and binocular visual acuities as measured by the Teller Acuity Cards
      are worse in premature infants than in full-term infants at the same
      chronological age. Poor visual acuity in premature infants can be attributed
      mainly to immaturity of the visual system.

PMID- 15564759
TI  - Development of a forced choice photographic questionnaire for photic phenomena
      and its testing - repeatability, reliability and validity.
AB  - AIM: To design, develop and test a system for analysis of photic phenomena.
      METHOD: Extensive background research, patient interviews and theoretical studies
      led to development of a set of photographic images resembling photic phenomena
      experienced by patients. These photographic images were processed and digitally
      altered to create scales of severity for each photic phenomenon in which patients
      indicated their severity of symptoms by choice of image. The system was tested
      for stability and validity. RESULTS: The system showed excellent repeatability
      and reliability. Face, content, criterion and construct validity were all found
      to be acceptable. CONCLUSION: The photographic images of photic phenomena
      analyser is an acceptable, validated measure for the assessment of photic
      phenomena, in both pseudophakic patients and those with cataract.

PMID- 15564760
TI  - TGFBI gene mutation analysis in families with hereditary corneal dystrophies from
      Ukraine.
AB  - In our study, 5 previously reported mutations of the TGFBI gene - R124C, R124H,
      R124L (exon 4), R555W, R555Q (exon 12) - were analyzed using polymerase chain
      reaction followed by restriction digestion in 48 individuals from 19 unrelated
      families with different forms of corneal dystrophy from different regions of
      Ukraine. The R555W mutation was detected in 6 patients from 4 families with
      granular corneal dystrophy. The R124C mutation was detected in 1 unaffected 10
      year-old individual and in 24 patients from 8 families with lattice corneal
      dystrophy. As far as the R124C mutation detected in 1 patient with clinically
      diagnosed Reis-Bucklers corneal dystrophy is concerned, we concluded that this
      patient was misdiagnosed. The obtained results show that TGFBI gene mutation
      analysis is important as well for the early differential diagnosis of corneal
      dystrophies and genetic consulting in high-risk families.

PMID- 15564761
TI  - Angiotensin-converting enzyme insertion-deletion polymorphism in primary open
      angle glaucoma.
AB  - PURPOSE: To investigate the hypothesis that primary open-angle glaucoma (POAG) is
      associated with a common insertion-deletion (I/D) polymorphism in the angiotensin
      converting enzyme (ACE) gene. METHODS: ACE I/D polymorphism was investigated in a
      control group of healthy subjects (n = 101) and in a group of patients diagnosed
      with POAG (n = 104). Polymerase chain reaction detection of I/D polymorphism was
      used to determine the presence of the two ACE alleles in the groups. RESULTS:
      Neither the I/D genotype distributions nor the allele frequencies differed
      significantly between POAG and control subjects (DD genotype 34.6 vs. 39.6%; ID
      genotype 53.9 vs. 40.6%; II genotype 11.5 vs. 19.8%, p = 0.1; D allele 61.5 vs.
      60%; I allele 38.5 vs. 40%, p = 0.8). CONCLUSION: We could not identify a
      possible association of the I/D polymorphism in the ACE gene with POAG, however
      further studies with larger patient numbers in different populations are required
      to clarify the role of ACE gene in susceptibility to POAG.

PMID- 15564762
TI  - The medial horn and capsulopalpebral fascia in the medial canthus are significant
      antagonists of the orbicularis oculi muscle for lacrimal drainage.
AB  - PURPOSE: The anatomical relationship indicates that the medial horn of the
      levator aponeurosis (MH) and the capsulopalpebral fascia (CPF) are the potential
      candidates for antagonists of the orbicularis oculi muscle (OOM). This study
      sought to disclose the relationships among the MH, CPF and OOM, and to discuss
      their roles in the lacrimal drainage system. METHODS: Twelve medial canthuses of
      6 cadavers were studied. After peeling eyelid skin from the OOM, we carefully
      observed the MH, CPF and OOM in the medial canthus. RESULTS: The MH attached to
      the superior aspect of the medial canthal tendon. The CPF, which attached to the
      lower tarsal margin, traveled just under Horner's muscle in the medial canthus
      and dispersed from a lateral aspect of the lacrimal sac to the posterior lacrimal
      crest. CONCLUSIONS: As the movement of a muscle can be determined by its origin
      and insertion, the MH and the CPF are considered to be the antagonists of the
      OOM, and as such must be taken into consideration for an understanding of the
      lacrimal drainage system.

PMID- 15564763
TI  - Systemic melanoma metastatic to the retina and vitreous.
AB  - PURPOSE: Report of a case of retinal and vitreous metastases of a systemic
      melanoma, possibly arising in the lung, that responded favourably to
      radiotherapy. CASE REPORT: Retinal and vitreous metastases were demonstrated in a
      57-year-old woman during routine follow-up after surgical resection of a melanoma
      presumed to be a primary pulmonary melanoma. After a 7-week observation period,
      which confirmed the progressive nature of the intra-ocular lesions, the patient
      was treated by external beam radiotherapy at a dose of 35 Gy delivered in 14
      fractions of 2.5 Gy. Complete disappearance of the vitreous invasion and
      progressive elimination of the retinal invasion were observed over a period of 9
      months. Final visual function was 20/25. REVIEW OF PUBLISHED CASES: A review of
      the literature identified 28 cases of melanoma with metastases to the retina and
      vitreous. In almost all of these cases, the primary tumour was a cutaneous
      melanoma and the mean patient survival following the diagnosis of intra-ocular
      metastases was 22 months. Retinal metastases, as in the case reported here,
      present a vascular tropism and tend to develop around veins. These metastases are
      generally unilateral and may be either solitary or multiple. Tumour invasion of
      the vitreous occurred by means of isolated cells forming a suspension of
      aggregates or spherules. Vitreous haemorrhage and irreducible neovascular
      glaucoma leading to functional impairment, which requires enucleation, were both
      the most frequent and the most serious complications of these metastases.
      Treatment is always palliative and is effective in cases with limited retinal and
      vitreous invasion, as in the case reported here. CONCLUSIONS: Metastatic melanoma
      in the retina and vitreous is a rare entity and can lead to functional impairment
      and enucleation because of neovascular glaucoma. As treatment is only effective
      in cases with limited invasion, systematic screening is recommended in all
      patients with a metastatic cutaneous melanoma presenting with suggestive ocular
      symptoms.

PMID- 15564764
TI  - Evolution of renal interstitial inflammation and NF-kappaB activation in
      spontaneously hypertensive rats.
AB  - Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive
      rats (SHR) and interventions leading to their reduction are associated with
      improvement of the hypertension. The present studies examined the evolution of
      the interstitial inflammation in the natural course of the SHR to gain insight on
      the potential role of interstitial immune cell accumulation in the development of
      hypertension. We studied SHR and control WKY rats at 3 weeks (SHR-3 wk group, n =
      11 and WKY-3 wk group, n = 10), 11 weeks (SHR-11 wk group, n = 5 and WKY-11 wk
      group, n = 5) and 24 weeks (SHR-24 wk group, n = 10 and WKY-24 wk group, n = 10).
      The SHR-3 wk group was normotensive and older SHR developed hypertension that was
      severe in the SHR-24 wk group. Tubulointerstitial accumulation of lymphocytes,
      macrophages, angiotensin II-positive cells, cells expressing the p65 DNA-binding
      subunit of NF-kappaB and activation of NF-kappaB in the kidney were all
      significantly increased (p < 0.01) in the prehypertensive SHR-3 wk group and
      augmented progressively, with the highest values in the SHR-24 wk group. The SHR
      24 wk group showed increased (p < 0.001) helper (CD4) T cell infiltration and a
      high CD4/CD8 ratio. These findings are consistent with the possibility that
      activation of NF-kappaB and renal interstitial infiltration of immune cells may
      be part of the pathophysiologic process that drives hypertension in the SHR.

PMID- 15564765
TI  - Long-term adaptation of renal ion transporters to chronic diuretic treatment.
AB  - Loop and thiazide diuretics are clinically useful to induce negative sodium
      balance. However, with chronic treatment, their effects tend to be blunted since
      the kidney adapts to diuretics. Molecular identification of the renal ion
      transporters has provided us with a new understanding of the mechanisms of
      intrarenal adaptation to diuretics at molecular levels. In the kidney, loop and
      thiazide diuretics are secreted from the proximal tubule via the organic anion
      transporter-1 (OAT1) and exert their diuretic action by binding to the Na-K-2Cl
      cotransporter type 2 (NKCC2) in the thick ascending limb and the Na-Cl
      cotransporter (NCC) in the distal convoluted tubule, respectively. Recent studies
      in animal models suggest that abundance of these ion transporters is affected by
      long-term diuretic administration. Downstream from the primary site of diuretic
      action, an increase in epithelial Na+ channel (ENaC) abundance is induced by
      chronic furosemide or hydrochlorothiazide treatment. This adaptation is
      consistent with previous reports showing cellular hypertrophy and increased Na+
      absorption in distal tubular segments. The abundance of NKCC2 and NCC is
      increased by furosemide and hydrochlorothiazide, respectively. This compensatory
      upregulation suggests that either diuretic may activate the ion transporter
      within the primary site of action. In the proximal tubule, the abundance of OAT1
      is increased by chronic treatment with furosemide or hydrochlorothiazide. This
      upregulation of OAT1 seems to be induced by substrate stimulation, lessening
      diuretic tolerance associated with long-term diuretic use.

PMID- 15564766
TI  - Indigestible components of grape seeds modify cecal enzyme activity in rats.
AB  - BACKGROUND: The effect of grape seed indigestible fraction (GSIF) on cecal enzyme
      activity was studied. METHODS: Beta-glucuronidase, beta-glucosidase,
      azoreductase, nitroreductase and nitrate reductase were measured in the cecal
      content of adult Wistar rats fed with a fiber-free diet supplemented with 5%
      cellulose or 5% GSIF as the source of dietary fiber for 4 weeks. RESULTS: The
      intake of GSIF did not affect body weight gain nor food intake. However, GSIF
      caused a significant increase in cecal content, cecal wall and fresh and dry
      stool weight. Bacterial enzyme activities were lower in the GSIF-fed group than
      in the cellulose-fed group, although the difference was also significant for
      nitroreductase and beta-glucuronidase. CONCLUSION: Adaptation to a diet
      containing GSIF led to changes in microbial activity that involved a decrease in
      reductive and hydrolytic enzymatic activities implicated in the conversion of
      procarcinogens into carcinogens.

PMID- 15564767
TI  - Effects of psyllium on plasma total and lipoprotein cholesterol and hepatic
      cholesterol in hamsters fed n-3 PUFA or n-6 PUFA with high cholesterol levels.
AB  - This study was conducted to determine whether psyllium is known to alter
      cholesterol metabolism modulate the hypercholesterolemic effect of a high
      cholesterol, n-3 polyunsaturated fatty acids (PUFA) diet in hamsters.
      Concentrations of plasma, hepatic total cholesterol and lipoprotein cholesterol
      were measured in male hamsters fed an n-3 PUFA plus psyllium (8%, wt/wt) diet
      combined with variable levels of cholesterol (0, 0.05, 0.1%, wt/wt) or a
      cholesterol-enriched (0.2%, wt/wt) n-3 PUFA or n-6 PUFA diet that contained
      either 8% methyl cellulose or psyllium for 4 weeks. In the n-3 PUFA-fed hamsters,
      we have found that psyllium was able to reduce plasma total cholesterol and low
      density lipoprotein (LDL)-cholesterol significantly when 0.1% cholesterol was
      added to the diet. In contrast, the effects of psyllium were not seen in the n-3
      PUFA-fed hamsters without dietary cholesterol or with 0.05% dietary cholesterol.
      However, no matter in the presence of psyllium or not, the increase of plasma
      total cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, LDL
      cholesterol and high-density lipoprotein (HDL)-cholesterol levels was depend on
      the content of dietary cholesterol. Although the cholesterol diet increased the
      liver total cholesterol level, 80 g psyllium/kg diet resulted in a significantly
      lower concentration of liver total cholesterol in the cholesterol-fed hamsters.
      In the second experiment, we have also found that psyllium feeding lowered
      significantly plasma total cholesterol and VLDL-cholesterol concentrations in
      hamsters fed n-3 PUFA but not in those fed n-6 PUFA. However, the levels of
      plasma total cholesterol, VLDL-cholesterol and LDL-cholesterol levels of the (n
      6) PUFA-fed hamsters were significantly lower than those in the (n-3) PUFA-fed
      hamsters in the absence or presence of dietary psyllium. Our data also showed
      that hamsters fed both high-cholesterol n-3 PUFA and n-6 PUFA diets had a
      significant decrease in hepatic cholesterol with intake of psyllium. Liver total
      cholesterol concentrations were significantly lower in n-3 PUFA-fed hamsters
      compared with the n-6 PUFA-fed groups. Therefore, these data may contribute to
      understanding the interactive effect of psyllium and cholesterol or the type of
      fat on plasma and liver cholesterol in hamsters.

PMID- 15564768
TI  - Monoclonal antibody-based ELISA to quantify the major allergen of Cynodon
      dactylon (Bermuda grass) pollen, Cyn d 1.
AB  - BACKGROUND: Pollen of Bermuda grass (Cynodon dactylon) is an important cause of
      pollinosis in many areas of the world. Most patients show sensitivity to the
      major allergen Cyn d 1, a glycoprotein composed of a number of isoforms with a
      molecular mass of 31-32 kDa. The aim of this work was to develop a monoclonal
      antibody (mAb)-based ELISA to quantify Cyn d 1, and to assess the correlation of
      the allergen content with the biological activity of C. dactylon pollen extracts.
      METHODS: After fusion of myeloma cells with spleen cells from a BALB/c mouse
      immunized with C. dactylon pollen extract, Cyn d 1-specific mAbs secreting
      hybridomas were selected, and the antibodies characterized. One of them (4.4.1)
      was used as the capture antibody in an ELISA method for Cyn d 1 quantitation. An
      anti-Cyn d 1 rabbit serum was used as the second antibody. Cyn d 1 was purified
      by immunoaffinity chromatography with mAb 4.4.1, characterized, and used as the
      standard in the assay. RESULTS: The identity, purity and isoallergen composition
      of affinity-purified Cyn d 1 was confirmed by N-terminal amino acid sequencing,
      SDS-PAGE, Western blot and 2D electrophoresis. The Cyn d 1 ELISA is highly
      specific and sensitive, with a detection limit of 0.24 ng/ml and a linear range
      of 1.1-9.2 ng/ml. An excellent correlation was found when the content of Cyn d 1,
      measured in 16 different extracts, was compared with the allergenic activity of
      the same extracts determined by RAST inhibition. CONCLUSIONS: The results prove
      the usefulness of the Cyn d 1 ELISA for the standardization of C. dactylon
      allergen products on the basis of major allergen content.

PMID- 15564769
TI  - Che a 1: recombinant expression, purification and correspondence to the natural
      form.
AB  - BACKGROUND: Pollinosis to chenopods is one of the main causes of allergy in
      desertic regions and it is increasing in the South of Europe and Western USA. Che
      a 1 is a major allergen for chenopod-allergic subjects and belongs to the Ole-e-1
      like family of proteins. METHODS: Pichia pastoris yeast has been used as
      expression system to produce the recombinant form of Che a 1 (rChe a 1). The
      allergen was isolated using a gel permeation column and reverse-phase/high
      performance liquid chromatography. Molecular characterization was performed using
      Edman degradation, mass spectrometry and concanavalin A staining. Sera from
      patients allergic to chenopod pollen, as well as polyclonal and monoclonal
      antibodies raised against Ole e 1, were used in immunoblotting, ELISA and
      inhibition assays for immunological characterization of rChe a 1. RESULTS: The
      allergen was purified to homogeneity with a final yield of 15 mg/l of cell
      culture and showed a glycosylated character. N-terminal amino acid sequence of
      rChe a 1 and molecular mass were according to those of the protein isolated from
      chenopod pollen. The recombinant allergen maintained the IgG and IgE epitopes of
      the natural allergen deduced from the immunological assays. CONCLUSIONS:
      Structural and in vitro immunological properties of rChe a 1 produced in P.
      pastoris were equivalent to those of the natural form of the allergen and, thus,
      it could be used in testing patients allergic to chenopods.

PMID- 15564770
TI  - Allergy to pigeon tick (Argas reflexus): demonstration of specific IgE-binding
      components.
AB  - BACKGROUND: The European tick, Argas reflexus, is an urban pest parasitizing
      urban pigeons and may cause a wide range of allergic reactions. METHODS: Specific
      IgE to A. reflexus, SDS-PAGE and IgE immunoblotting, performed with tick extract,
      were carried out in the sera of 6 patients who reported allergic reactions after
      tick bite. RESULTS: Specific IgE to A. reflexus (RAST class ranging from 1 to 3)
      were detected in the sera of 6 patients who reported allergic reactions
      (urticaria and angioedema in 2 and anaphylaxis in the other 4 patients) after
      tick bite. IgE reactivity to two bands of 22 and 40 kDa were identified in the
      patient sera. CONCLUSIONS: Allergy to A. reflexus has to be considered in
      allergic patients living in buildings where pigeons have their nests. The
      powerful sensitizing property of tick allergen is underlined by the observation
      that none of our patients was atopic.

PMID- 15564771
TI  - Staphylococcal enterotoxin-B-mediated stimulation of interleukin-13 production as
      a potential aetiologic factor in eczema in infants.
AB  - BACKGROUND: Staphylococcus aureus colonization has been found in 80-100% of
      lesional skin from patients with atopic eczema dermatitis syndrome (AEDS) and is
      thought to have a role in the pathogenesis of the disease. Furthermore, up to 65%
      of S. aureus from lesional skin has been shown to produce toxigenic
      superantigens. METHODS: Using a cohort of 11 children under 2 years of age
      diagnosed with AEDS, we isolated peripheral blood mononuclear cells, cultured
      them with staphylococcal enterotoxin B (SEB) and phytohaemagglutinin, and
      assessed the cytokine response profiles. Plasma was also collected for
      immunoglobulin E analysis. In addition, skin and nasal swabs were taken and
      cultured to determine the presence of SEB-producing S. aureus by polymerase chain
      reaction (PCR) and reverse passive latex agglutination. RESULTS: We found a
      significant increase in the production of the SEB-induced cytokines interleukin
      (IL)-5 and IL-13 in the patient group when compared with non-atopic, healthy
      controls. For IL-13, there was almost no overlap in the levels between the
      groups. However, there was no correlation between SEB-induced IL-13 and disease
      severity. This difference was not seen when heat-inactivated S. aureus was used
      to stimulate the cells. CONCLUSIONS: IL-13 is an important factor in AEDS
      development in early childhood, and prophylactic anti-staphylococcal treatment
      may provide protection from AEDS in atopic individuals.

PMID- 15564772
TI  - Desloratadine inhibits constitutive and histamine-stimulated nuclear factor
      kappaB activity consistent with inverse agonism at the histamine H1 Receptor.
AB  - BACKGROUND: The human histamine H1 receptor is constitutively active and exhibits
      basal activation of nuclear factor-kappaB (NF-kappaB), an important modulator of
      allergic inflammation. Certain H1 antihistamines have recently been shown to
      inhibit basal NF-kappaB activity by stabilizing the H1 receptor in an inactive
      state, a phenomenon called 'inverse agonism'. METHODS: We evaluated the effect of
      the new H1 antihistamine, desloratadine, on basal and histamine-stimulated NF
      kappaB activity and compared it with the activities of other H1 antihistamines.
      RESULTS: Transiently transfected COS-7 cells co-expressing NF-kappaB-luciferase
      and the H1 receptor exhibited constitutive NF-kappaB activity. H1 antihistamines
      reduced basal NF-kappaB activity (rank order of potency: desloratadine >
      pyrilamine > cetirizine > loratadine > fexofenadine). Histamine stimulated basal
      NF-kappaB activity 8-fold, which was blocked by H1 antihistamines (rank order of
      potency: desloratadine > cetirizine > pyrilamine > loratadine > fexofenadine).
      Neither histamine nor antihistamines had any effect on NF-kappaB activity in the
      absence of the H1 receptor. CONCLUSIONS: Desloratadine, acting through the
      histamine H1 receptor, inhibited basal NF-kappaB activity and can thus be
      classified as an inverse agonist. Inhibition of basal and histamine-stimulated NF
      kappaB activity may help to explain previously reported inhibitory effects of
      desloratadine on allergic inflammatory mediators.

PMID- 15564773
TI  - A comprehensive analysis of interleukin-4 receptor polymorphisms and their
      association with atopy and IgE regulation in childhood.
AB  - BACKGROUND: The interleukin (IL) 4/IL13 pathway is involved in the regulation of
      IgE production associated with atopic diseases. Numerous polymorphisms have been
      identified in the coding region of the IL4 receptor alpha chain (IL4Ra) and
      previous association studies have shown conflicting results. Based on their
      putative functional role, polymorphisms A148G, T1432C and A1652G, located in the
      coding region of IL4Ra, were selected for association and haplotype studies in a
      large German population sample (n = 1,120). METHODS: Genotyping was performed
      using allele-specific PCR and restriction-enzyme-based assays. Haplotypes were
      estimated, and population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE
      >115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome variables in a
      haplotype trend regression analysis. RESULTS: In our population, only
      polymorphism T1432C showed a trend for a protective effect against atopic
      rhinitis (odds ratio, OR: 0.52, 95% confidence interval, CI: 0.26-1.02, p =
      0.05). When haplotypes were calculated, one haplotype was significantly
      associated with elevated serum IgE levels at the 50th percentile (OR 1.60, 95% CI
      1.08-2.37, p = 0.02). CONCLUSIONS: These data indicate that IL4Ra polymorphisms,
      although suggested to be functionally relevant by in vitro studies, have only a
      minor influence on IgE regulation in our large population sample.

PMID- 15564774
TI  - Are single nucleotide polymorphisms of the immunoglobulin A Fc receptor gene
      associated with allergic asthma?
AB  - BACKGROUND: Eosinophils are important components of allergic inflammation. The
      immunoglobulin A (IgA) Fc receptor (FcalphaRI), encoded by the FCAR gene, is a
      possible candidate for eosinophil activation at mucosal surfaces, where IgA is
      abundant. Both elevated cell surface expression of FcalphaRI and increased
      avidity for IgA were described on eosinophils from allergic subjects. The aim of
      our study was to examine the possible association of FCAR gene polymorphisms with
      allergic asthma. METHODS: We screened three regions of the FCAR gene: (1) the
      promoter region, (2) exon 3, encoding the first extracellular domain (EC1), and
      (3) exon 5, coding for the transmembrane and cytoplasmic domain, for new and
      published polymorphisms using a sensitive temperature gradient gel
      electrophoresis technique and compared their frequencies in 112 patients
      diagnosed with allergic asthma and 100 healthy controls. RESULTS: Six
      polymorphisms, including two novel ones, were detected. No differences between
      patients and controls were found in the distribution of any of these
      polymorphisms. CONCLUSION: FcalphaRI polymorphism does not seem to be a risk
      factor in allergic asthma. Nevertheless, this is the first report on the
      distribution of 6 single nucleotide polymorphisms of the FCAR gene in a human
      population and the first study on FCAR polymorphism in allergic asthma.

PMID- 15564775
TI  - Efficacy of injection immunotherapy with ragweed and birch pollen in elderly
      patients.
AB  - BACKGROUND: The role of specific immunotherapy (SIT) in elderly allergic patients
      is still debated. OBJECTIVE: The aim of this study was to assess whether SIT is
      associated with a better control of symptoms and a better quality of life also in
      older allergic patients. METHODS: The effect of injection SIT was assessed in 39
      patients [age >54 years, median 59; 29 patients (74%) with asthma, otherwise
      healthy] monosensitized to birch (n = 20) and ragweed (n = 19). Thirty-three
      younger subjects [age <50 years, median 35; 26 patients (79%) with asthma,
      otherwise healthy] monosensitized to birch (n = 10) and ragweed (n = 23), and 37
      subjects >54 years old (25 males/12 females; age 55-79 years, median 59 years)
      monosensitized to birch (n = 18) and ragweed (n = 19) who refused to undergo SIT
      were enrolled as positive and negative controls, respectively. All groups had a
      disease duration <10 years; the disease was inadequately controlled with standard
      drug therapies in all cases. SIT was carried out using the same extracts and was
      administered using a perennial schedule both in patients and controls. Seasonal
      therapies were the same in all groups and were not changed after SIT was started.
      After 1-5 years of SIT, patients and controls were asked to quantify symptom
      reduction on a visual analogue scale: reductions >50% were considered
      significant. Moreover, the use of cetirizine and/or salbutamol as an adjunct to
      standard therapies during the last pollen season was assessed as an objective
      measure of SIT outcome. RESULTS: 37/39 (95%) patients versus 32/33 (97%) controls
      submitted to SIT reported a symptom reduction >50% after 1-5 years of SIT
      (nonsignificant). The median clinical efficacy of SIT was 80% in both groups
      (nonsignificant). 27/37 controls not submitted to SIT did not report any change
      in symptom severity at the follow-up visits, whereas 10/37 reported a more severe
      disease (4 subjects reported the appearance of seasonal asthma) (p < 0.001 vs.
      patients submitted to SIT). Patients used less frequently cetirizine (p < 0.001)
      and/or salbutamol (p < 0.05) than controls not submitted to SIT. CONCLUSION:
      Injection SIT can be considered an effective therapeutic option in otherwise
      healthy elderly patients with a short disease duration whose symptoms cannot be
      adequately controlled by drug therapies alone.

PMID- 15564776
TI  - The allergic march in pollinosis: natural history and therapeutic implications.
AB  - BACKGROUND: That specific immunotherapy (SIT) can slow the march of allergy has
      been confirmed in controlled clinical trials. However, an assessment of its
      effects in everyday life, in a large cohort of patients, might provide further
      useful information. METHODS: This observational study comprised 3,643 patients
      allergic to pollens; 1,620 with pure allergic rhinitis or rhinitis and
      intermittent or mild-persistent bronchial asthma, responding poorly to standard
      pharmacological therapy (SPT), were treated for 3 years with SPT alone (pure
      rhinitis, n = 890), or combined with continuous SIT (rhinitis and asthma, n =
      730). Symptom/drug scores were recorded, respiratory function and skin tests were
      done, and methacholine challenge was scheduled at the beginning and end of the
      study. A series of 2,023 patients with pure rhinitis, responsive to SPT, were
      asked to 'self-medicate' as needed, serving as a control group to check the
      incidence of asthma. RESULTS: The incidence of rhinitis-asthma co-morbidity was
      highest in the self-medication group (50.8%). Persistent rhinitis was associated
      with asthma more often than the intermittent form, regardless of the severity of
      the symptoms that led to progression to asthma in patients with intermittent
      rhinitis. Treatment with SIT combined with SPT always slowed the allergic march
      which, however, was not influenced by drugs alone. CONCLUSIONS: In routine
      clinical practice, SIT is effective in preventing the allergic march. Patients
      with persistent rhinitis, who are at greatest risk of progression to asthma,
      appear to be the most logical candidates.

PMID- 15564777
TI  - Japanese cedar-pollen-specific IL-5 production in infants with atopic dermatitis.
AB  - BACKGROUND: Although food allergens and house dust mites are thought to
      contribute to the development of atopic dermatitis (AD) in infants, the influence
      of pollens has not yet been well defined. OBJECTIVE: This study attempted to
      clarify the effect of Japanese cedar pollens (JCPs), which are scattered in Japan
      between February and April, on AD in infants. METHODS: In the first study,
      seasonal changes in the number of patients who first visited our institute due to
      AD were analyzed by reviewing medical records of 184 infants with AD. In the
      second study, peripheral blood mononuclear cells from 81 children (50 infants <1
      year and 31 older children) with AD were stimulated with a standardized JCP
      allergen. The production of IL-5 was measured and its correlation with the
      severity of AD in infants was analyzed. RESULTS: The number of infants who first
      visited the institute due to AD peaked in spring. JCP-specific IL-5 production
      began to increase immediately after the first contact with JCPs in infants with
      AD. The production of IL-5 in infants with AD exposed to JCPs was significantly
      higher than in control subjects (p < 0.002) or in AD infants never exposed to
      JCPs (p < 0.02). There was a significant positive correlation between IL-5
      production and the severity of AD in infants (p < 0.0001). CONCLUSION: These
      results suggest that JCPs play an important role in the aggravation of infantile
      AD in spring by inducing IL-5 production.

PMID- 15564778
TI  - Upregulation of interleukin-13 and its receptor in a murine model of bleomycin
      induced scleroderma.
AB  - BACKGROUND: Interleukin-13 (IL-13) has been implicated in the pathogenesis of
      fibrotic conditions. Previously, a murine model for scleroderma has been
      established by repeated local injections of bleomycin. This animal model enabled
      us to study local expression and production of IL-13 in skin lesions during
      disease progression. METHODS: Dermal sclerosis (DSc) was induced by repeated
      subcutaneous injections of bleomycin (1 mg/ml) in C3H/HeJ mice. IL-13 and IL-4
      expressions were examined by RT-PCR, ELISA and immunohistochemistry. RESULTS: RT
      PCR showed that both IL-4 and IL-13 mRNA levels in skin lesions were increased
      and peaked after 4 weeks of bleomycin treatment. Quantification by densitometry
      revealed up to 4.2- and 1.9-fold increases, respectively. Immunohistochemical
      localization showed in skin lesions expression of IL-13 on infiltrating
      inflammatory cells, including mononuclear cells and possibly mast cells,
      increased with DSc progression. IL-13 protein production was also significantly
      increased. In skin lesions, IL-13 receptor (IL-13R) alpha2 expression was
      augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin
      exposure. IL-13Ralpha2, but not IL-13Ralpha1, mRNA was upregulated in the whole
      skin after 4 weeks. On the contrary, mRNA expression of IL-13Ralpha1 and IL-
      13Ralpha2 was significantly altered in the cultured fibroblasts derived from
      bleomycin-treated skin. CONCLUSION: These data demonstrate that in skin lesions
      levels of IL-13 as well as its receptor increase in parallel with DSc
      progression, suggesting that IL-13 promotes the progression of cutaneous
      fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma.

PMID- 15564779
TI  - Life-long echoes--a critical analysis of the developmental origins of adult
      disease model.
AB  - The hypothesis that there is a developmental component to subsequent adult
      disease initially arose from epidemiological findings relating birth size to
      either indices of disease risk or actual disease prevalence in later life. While
      components of the epidemiological analyses have been challenged, there is strong
      evidence that developmental factors contribute to the later risk of metabolic
      disease--including insulin resistance, obesity, and heart disease--as well as
      have a broader impact on osteoporosis, depression and schizophrenia. We suggest
      that disease risk is greater when there is a mismatch between the early
      developmental environment (i.e., the phase of developmental plasticity) versus
      that experienced in mature life (i.e., adulthood), and that nutritional
      influences are particularly important. It is also critical to distinguish between
      those factors acting during the developmental phase that disrupt development from
      those influences that are less extreme and act through regulated processes of
      epigenetic change. A model of the relationship between the developmental and
      mature environment is proposed and suggests interventional strategies that will
      vary in different population settings.

PMID- 15564780
TI  - Asymmetry of cerebral blood flow velocity in low birth weight infants.
AB  - BACKGROUND: In premature infants, intraventricular hemorrhage occurs more
      commonly in the left than the right hemisphere. We have demonstrated previously
      that cerebral blood flow velocity is lower in the left than the right middle
      cerebral artery in the first few hours after birth. This may be due to the open
      ductus arteriosus. OBJECTIVE: To test the hypothesis that blood flow velocity is
      lower in the left than the right middle cerebral artery only when the ductus
      arteriosus is open. STUDY DESIGN: Infants born at 25-33 weeks' gestation were
      enrolled. Middle cerebral artery blood flow velocities and coefficients of
      variation were measured on the left, followed by the right, on days 1 and 7 of
      life. Echocardiography identified 67 infants (25-33 weeks, 517-2,371 g) whose
      ductus arteriosus was open on day 1 and closed on day 7. RESULTS: Systolic (26.4
      +/- 7.4 vs. 29.6 +/- 7.2 cm/s), mean (12.4 +/- 4.0 vs. 15.6 +/- 4.6 cm/s) and end
      diastolic (5.3 +/- 2.2 vs. 6.8 +/- 2.9 cm/s) blood flow velocities were lower (p
      < 0.01) and the corresponding coefficients of variation were higher (p < 0.01) on
      the left on day 1. Neither the absolute Doppler blood flow velocities nor the
      coefficients of variation differed between the left and right sides on day 7.
      CONCLUSIONS: Blood flow velocity is lower and more variable in the left compared
      to the right middle cerebral artery on day 1 of life in premature infants. These
      differences are not found on day 7. We speculate that this difference is due to
      the associated ductus arteriosus patency.

PMID- 15564781
TI  - Transcription factors NF-kappaB and C/EBPdelta and IL-1-induced expression of
      surfactant protein A in lung explants during the perinatal period.
AB  - Interleukin-1 (IL-1) increases the expression of surfactant protein A (SP-A) in
      rabbit, lamb and human fetal lung. The upregulation disappears towards term.
      Among the transcription factors, IL-1 activates nuclear factor kappaB (NF-kappaB)
      and CCAAT/enhancer-binding protein delta (C/EBPdelta). NF-kappaB presumably has a
      role in IL-1-induced upregulation of SP-A. Also, C/EBPdelta may regulate SP-A
      expression. The aim was to study the role of these transcription factors in the
      induced effect of IL-1 on SP-A expression. Explants from fetal and neonatal
      rabbit lung were cultured in vitro followed by studies using
      immunohistochemistry, electrophoretic mobility shift assay and Northern analysis.
      We found gestation-dependent changes in IL-1-induced immunoreactivities of NF
      kappaB and C/EBPdelta in the nuclei of alveolar cells. This increase in nuclear
      transcription factors correlated with IL-1-induced SP-A expression levels. As
      studied in the explants from fetal and newborn lung, the SP-A mRNA expression
      additionally associated with C/EBPdelta mRNA and with the binding of nuclear
      extracts from the lung explants to the C/EBP consensus probe. On the basis of the
      present and previous studies, we propose that NF-kappaB and C/EBPdelta have
      potential mediator roles in IL-1-induced upregulation of SP-A in immature lung.

PMID- 15564782
TI  - Novel insertion 496_497insG creating a stop codon D194X in a Chinese family with
      X-Linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (XALD, MIM 300100), the commonest inherited
      peroxisomal disorder, is characterized by central nervous system demyelination,
      primary adrenal failure and the systemic accumulation of saturated very long
      chain fatty acids (VLCFAs). The defective gene ABCD1 encodes an ATP-binding
      cassette (ABC) transport protein named ALDP, which functions as a crucial
      transporter of VLCFAs into the peroxisomes for beta-oxidation. Here, we report a
      Chinese man with adrenomyeloneuropathy characterized by Addison's disease and
      spastic paraparesis. His plasma VLCFA levels, ratios of C24:0/C22:0 and
      C26:0/C22:0 were all significantly elevated. We performed mutation analysis of
      the ABCD1 gene in the proband and the family members using direct DNA sequencing
      and restriction analysis. A novel insertion 496_497insG in exon 1 causing a frame
      shift and a premature stop codon at amino acid position 194 (D194X) was
      identified (GenBank accession No. NM_000033). The insertional mutation abolishes
      an HhaI restriction site. The same mutation was found in his mother and the
      eldest sister even though their clinical and biochemical abnormalities were
      milder. Diagnosis of XALD often relies upon the detection of elevated VLCFA
      levels and ratios of C26:0/C22:0 and C24:0/C22:0 in fasting blood, however, 5-15%
      of the obligate heterozygotes would give normal values. DNA-based testing thus
      remains the most reliable tool for heterozygote detection when the disease
      causing mutations are known. Using restriction fragment length polymorphism with
      HhaI, we have devised a rapid method for the identification of the carriers among
      the proband's family members and possibly for the screening of the mutations in
      other XALD patients.

PMID- 15564783
TI  - Homologous up-regulation of androgen receptor expression by androgen in vascular
      smooth muscle cells.
AB  - OBJECTIVE: Androgens play an important role in the arterial vascular system, and
      androgen receptors (AR) have been identified in vascular smooth muscle cells
      (VSMCs). This study examined the effects of testosterone exposure on AR gene
      expression in cultured rat aortic smooth muscle cells. METHODS: Changes in AR
      protein and messenger RNA (mRNA) levels after androgen exposure were determined
      using immunoblotting and Northern blotting analysis respectively. RESULTS:
      Treatment of synchronized VSMCs with testosterone increased both cytoplasmic and
      nuclear AR protein expression in a dose- and time-dependent fashion, whereas
      exposure of VSMCs to androgen for 10 min induced a transient down-regulation of
      AR protein. Meanwhile, AR mRNA level was also up-regulated, but to a much smaller
      extent. Pretreatment with transcription inhibitor and translation inhibitor
      repressed cytoplasmic AR protein levels to 46 and 12% (means) of the androgen
      treatment control level respectively. Furthermore, androgen up-regulation of
      intracellular AR protein was partially inhibited by androgen antagonist.
      CONCLUSIONS: Androgen increases AR expression in VSMCs at the level of both
      transcription and non-transcription.

PMID- 15564784
TI  - Robot-assisted laparoscopic Heller cardiomyotomy: preliminary UK results.
AB  - BACKGROUND/AIM: Laparoscopic Heller cardiomyotomy is an established modality in
      the surgical treatment of patients having achalasia cardia. We present our
      initial experience in robot-assisted laparoscopic Heller cardiomyotomy without
      addition of an antireflux procedure and discuss the relative merits and
      disadvantages of the procedure. PATIENTS AND METHODS: Five patients underwent
      robot-assisted laparoscopic Heller cardiomyotomy between August 2001 and October
      2002. The diagnosis had been confirmed by radiology and manometry in all patients
      prior to surgery. RESULTS: All procedures were completed successfully using the
      robotic system, without conversion to open procedure. Mucosal perforation
      occurred in 1 patient and was sutured robotically. The average operative time was
      114.8 (range 65-160) min which is comparable to laparoscopic procedures. After a
      mean follow-up period of 9.4 (range 3-17) months, 4 patients remained completely
      asymptomatic, and 1 patient has benefited from symptomatic improvement.
      CONCLUSIONS: The enhanced dexterity and the high-quality three-dimensional vision
      available with robot-assisted surgery make the application of this technology
      highly suitable for Heller cardiomyotomy. The minimal lateral and posterior
      dissection due to the wristed instruments avoids the need for an antireflux
      procedure.

PMID- 15564785
TI  - Treatment of postoperative enterocutaneous fistulas by high-pressure vacuum with
      a normal oral diet.
AB  - BACKGROUND/AIMS: Enterocutaneous fistulas are associated with prolonged hospital
      stay, high morbidity/mortality, and increased hospital costs. This study aims to
      describe the use of a vacuum system and normal oral diet in dealing with this
      problem. METHODS: Seventy-four consecutive patients with recent and defined
      external postoperative fistulas were analyzed. Abdominal imaging was used to
      exclude abscess and distal obstruction. The fistula tract was sealed with Foley
      catheter, connected to a negative pressure flask, changed daily for 5, 10 or 15
      days, as necessary. A normal oral diet was permitted. RESULTS: No patient died.
      Serum albumin and transferrin showed significantly higher levels at the end of
      treatment than at the beginning. The moderate and low-output fistulas had the
      best results (97% closed). Forty-eight (65%) fistulas closed after 5 days, 16
      (22%) after 10 days and 4 (5%) after 15 days. Treatment failed in 6 (8%)
      patients, who subsequently underwent surgery. The fistula did not close in 1
      patient with a low output. The cost of the treatment was USD 41.75/day and it was
      considered cost-effective. CONCLUSIONS: The vacuum system demonstrated good
      results in the treatment of fistulas. It included simplicity, low cost, short
      hospital stay, absence of skin breakdown, normal eating, good nutrition and
      activity patterns.

PMID- 15564786
TI  - Influence of surgeon volume on clinical and economic outcomes of laparoscopic
      cholecystectomy.
AB  - BACKGROUND AND PURPOSE: The volume-outcome effect has been well documented in
      both medical treatment and surgery. The relationship of volume-outcome
      utilization in laparoscopic cholecystectomy has not been studied. The aims of
      this study were to examine whether the operational volume of individual surgeons
      is associated with the clinical and economic outcomes of patients with
      gallbladder diseases undergoing laparoscopic cholecystectomy. METHODS: A
      retrospective study was made of all patients who underwent elective laparoscopic
      cholecystectomy in the Department of Surgery, Kaohsiung Medical University
      Hospital between January 1998 and April 2002. In total, 916 patients were
      operated on by 4 surgeons and the volume for each surgeon was 502, 192, 147, and
      75 cases, respectively. Clinical and economic information for each patient was
      abstracted from medical charts and the financial division. Multiple logistic and
      linear regression models were used to examine the relationship between three
      outcome variables, complications, length of stay, total hospital charges, and
      surgeon volume while controlling for the severity of illness and other selected
      covariates (morbidity index). RESULTS: Overall, a complication rate of 1.2% was
      identified. On average, the patient's stay in hospital was 4.7 days, and the
      average total hospital charge was TWD 49,581. After adjusting for covariates,
      three regression models indicated that the surgeon with the highest volume had
      the lowest complication rate, shortest length of stay, and lowest hospital
      charges. CONCLUSIONS: The operative volume of individual surgeons not only had a
      positive impact on clinical outcomes, it also had greater effect on conservation
      of health care resources. The findings validate the theory of practice makes
      perfect.

PMID- 15564787
TI  - Correlation between dynamic computed tomographic and histopathological findings
      in the diagnosis of small hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: To determine the characteristic image findings on dynamic
      computed tomography (CT) for small hepatocellular carcinoma (HCC), we evaluated
      the correlation of histopathological and radiological findings with respect to
      the angioarchitecture in small HCCs. METHODS: CT and early- and late-phase
      dynamic CT findings of 80 small HCCs (< or =3 cm) were divided into iso-, high,
      low, and mixed density. We studied the correlation between the imaging findings
      and the histopathological findings as follows: differentiation grade; presence of
      fibrous capsule; presence of Glisson's sheath, and growth pattern. RESULTS: High
      density early-phase CT and low-density late-phase CT correlated significantly
      with moderately/poorly differentiated HCCs, which have a fibrous capsule, no
      Glisson's sheath, and an expansive growth pattern. In contrast, well
      differentiated HCCs with a Glisson's sheath and a replacing pattern (early HCC)
      appeared as iso-dense lesions in the early and late phases. Well-differentiated
      HCCs (non-early wHCC) demonstrated various density images in the early phase and
      low-density images in the late phase. CONCLUSIONS: Dynamic CT is an economic and
      simple diagnostic tool for planning treatment of small HCC lesions because of the
      multistep nature of HCC carcinogenesis and the hemodynamic changes of tumor blood
      flow.

PMID- 15564788
TI  - Are prostanoids related to positive inotropism by UTP and ATP?
AB  - Uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) induce biphasic
      inotropic effects: first a decrease and then an increase in contractile tension
      were observed in isolated rat myocardial tissues. Inotropic effects were higher
      in atrial tissue than in ventricular or papillary muscle; thus, experiments were
      mostly carried out on rat atria. In this research, we mainly studied positive
      inotropism by using selective inhibitors of the arachidonic acid cascade. The
      natural compounds luffariellolide and aristolochic acid, two inhibitors of PLA2,
      both inhibited positive inotropism by UTP but not by ATP, whereas they did not
      modify their negative inotropism. Indomethacin (5 micromol/l), an inhibitor of
      COX-1, reduced positive inotropism by UTP but not by ATP, without modifying their
      negative inotropism. Nimesulide (1 micromol/l), an inhibitor of COX-2, did not
      change any of the effects caused by nucleotides. Nor did NDGA (10 micromol/l), an
      inhibitor of lipoxygenase, change inotropism by nucleotides. Arachidonic acid
      pretreatment (10 micromol/l) increased inotropic effects by UTP without affecting
      those of ATP. These data suggest that there are differences in the mechanisms
      responsible for the positive inotropism caused by UTP in comparison with ATP; the
      effect of UTP depends on PLA2 activation and PG(s) release, whereas that of ATP
      does not.

PMID- 15564789
TI  - Hypothalamic antihypertensive effect of irbesartan in chronic aortic coarctated
      rats.
AB  - The aim of the present work was to study the central and plasma pharmacokinetics
      of irbesartan (IRB) and its possible hypothalamic antihypertensive effect in sham
      operated (SO) and aortic-coarctated (ACo) rats at a chronic hypertensive stage
      using the microdialysis technique. Anesthetized Wistar rats were used 42 days
      after ACo or SO. For the study of plasma pharmacokinetics, a vascular shunt probe
      was inserted into the carotid artery. In a separated experiment, a concentric
      probe was placed into the anterior hypothalamus for the study of IRB distribution
      in the central nervous system. Based on the hypothalamic concentrations of IRB
      reached in ACo rats, the anterior hypothalamus of SO and ACo animals was perfused
      with a Ringer solution containing approximately 6 microg x ml(-1) of the drug.
      IRB (10 mg x kg(-1) i.v.) induced a late decrease of heart rate (HR) in ACo
      animals (DeltaHR: -42 +/- 10 bpm, n = 5, p < 0.05 vs. SO rats) but not in SO rats
      (DeltaHR: 11 +/- 13 bpm, n = 5). Systemic administration of the drug reduced the
      mean arterial pressure (MAP) of both experimental groups, but the hypotensive
      effect was greater in ACo (DeltaMAP: -39.9 +/- 5.0 mm Hg, n = 5, p < 0.05 vs. SO
      rats) than in SO rats (DeltaMAP: -25.4 +/- 2.1 mm Hg, n = 5). A similar
      pharmacokinetic profile was observed in both experimental groups. Hypothalamic
      distribution of IRB was greater in ACo (AUC: 730 +/- 130 ng x ml(-1) h(-1), n =
      5, p < 0.05 vs. SO rats) than in SO animals (AUC: 283 +/- 87 ng x ml(-1) h(-1), n
      = 5). The IRB hypothalamic perfusion induced an antihypertensive effect in ACo
      (DeltaMAP: -15.1 +/- 1.0 mm Hg, n = 5, p < 0.05 vs. Ringer perfusion) but not in
      SO rats. In conclusion, the chronic aortic coarctation did not modify the plasma
      pharmacokinetics of IRB, but it increased the distribution of the drug in the
      central nervous system. The greater hypotensive effect of IRB observed in ACo
      animals suggests the involvement of AT1 receptors in the maintenance of the
      hypertensive stage in chronic ACo rats. The hypotensive effect of IRB in ACo
      animals could be explained, at least in part, due an action on the anterior
      hypothalamic angiotensin system.

PMID- 15564790
TI  - Fear of intimacy in women: relationship between attachment styles and depressive
      symptoms.
AB  - BACKGROUND: Preoccupied and fearful attachment have both been associated with
      depressive symptoms, but it is unclear which attachment style is primarily
      associated with major depression. While preoccupied attachment denotes a focus on
      relationships as a source of self-validation, fearful attachment involves an
      avoidance of relationships for fear of rejection. Present research aims to
      investigate the relative influence of fearful and preoccupied attachments on self
      reported depressive symptoms within both a student and a clinical sample and to
      examine these associations separately for male and female participants. SAMPLING
      AND METHODS: All participants completed the Relationship Questionnaire and the
      Beck Depression Inventory. Study 1 assessed attachment ratings and self-reported
      severity of depression for 71 patients diagnosed with major depression. Study 2
      similarly assessed 245 university students, and study 3 compared attachment
      ratings of the two samples. RESULTS: Both Pearson correlations and partial
      correlations were examined for both samples. Fearful attachment was associated
      with self-reported depression severity for females with depression, but
      attachment styles were unrelated to depression severity for males with depression
      (study 1). For female university students, both fearful and preoccupied
      attachment styles were significantly related to depression severity, but again
      there were no associations for male university students when partial correlations
      were utilised (study 2). Study 3 revealed significantly higher levels of fearful
      attachment for women with depression compared with female university students and
      no significant differences for males overall. CONCLUSIONS: For females, the
      avoidance of intimacy for fear of rejection was associated with a broad spectrum
      of depressive symptoms. Results highlight gender differences in depressive
      experiences, and have implications for research into the effects of fearful
      attachment on social support and the therapeutic alliance. Limitations to this
      study include the reliance on self-report measures of attachment and depression
      severity, the small number of male participants in the clinical sample, and the
      use of a cross-sectional rather than longitudinal design.

PMID- 15564791
TI  - Benevolent voices are not so kind: the functional significance of auditory
      hallucinations.
AB  - BACKGROUND: This study measures the impact of beliefs about auditory
      hallucinations on social functioning. SAMPLING AND METHODS: Twenty-nine subjects
      who met the ICD-10 criteria for schizophrenia or a schizo-affective disorder were
      included. Beliefs about voices and coping responses as measured by the Beliefs
      about Voices Questionnaire were compared with social functioning as assessed with
      the Life Skills Profile (LSP). RESULTS: The belief that voices are benevolent was
      associated with poor communication. Engagement with voices was correlated with
      the non-turbulence and the compliance factors of the LSP. Patients who held the
      belief that their voices were benevolent functioned significantly more poorly on
      the communication factor of the LSP than patients who interpreted their voices as
      malevolent. DISCUSSION: The results indicate that a positive relationship with
      voices may affect social functioning. However, the size of the sample is small
      and patients with benevolent voices are overrepresented. Nonetheless, these
      results have implications for the use of cognitive therapy for psychotic
      symptoms.

PMID- 15564792
TI  - Differential expression of L- and T-type calcium channels between longitudinal
      and circular muscles of the rat myometrium during pregnancy.
AB  - The aim of this study was to evaluate the difference in the expression of mRNA of
      two types of calcium channels between longitudinal and circular muscle layer of
      rat myometrium during pregnancy. Changes in the expressions of the mRNA encoding
      L-type (alpha1C) and T-type (alpha1G, alpha1H, and alpha1I) calcium channels in
      longitudinal and circular smooth muscle cells of the rat myometrium were examined
      using a comparative kinetic RT/PCR method. During the course of pregnancy,
      alpha1C mRNA expression showed an N-shaped change in longitudinal muscle, but
      simply increased after mid-pregnancy in circular muscles. The mRNAs for alpha1G
      and alpha1H, but not that for alpha1I, were expressed in both longitudinal and
      circular smooth muscle. In longitudinal muscle, the change in alpha1H mRNA was
      similar to that in alpha1C mRNA during gestation, but the expression of alpha1G
      mRNA changed significantly only at term (day 22). In circular muscle, alpha1H
      mRNA expression was stable at any stage during pregnancy, but alpha1G mRNA
      significantly increased on day 15 and at term. No relationship was observed
      between voltage-dependent calcium-channel mRNA expressions and either
      proliferation or hypertrophy of circular muscle during pregnancy. These results
      show (a) that during pregnancy, the expression levels of L-type channels change
      dynamically, and it may contribute directly to the regulation of cell
      excitability, and (b) that the T-subtype that increases during pregnancy differs
      between longitudinal and circular muscle cells, although their functions remain
      unclear.

PMID- 15564793
TI  - Response to fulvestrant in heavily pretreated postmenopausal women: a single
      center experience.
AB  - Fulvestrant ('Faslodex') is a new estrogen receptor (ER) antagonist that has no
      agonist effects. It binds, blocks and accelerates degradation of the ER, leading
      to a complete abrogation of estrogen-sensitive gene transcription. In
      postmenopausal women with advanced breast cancer progressing on prior endocrine
      therapy, fulvestrant is at least as effective as the third-generation aromatase
      inhibitor (AI) anastrozole. In this single-center experience, 42 postmenopausal
      patients with metastatic breast cancer who had been heavily pretreated with prior
      endocrine therapy and chemotherapy were treated with fulvestrant. Prior endocrine
      therapies included selective ER modulators (including tamoxifen and toremifene),
      AIs, megestrol acetate, and high-dose estrogens. In total, eight patients (19%)
      achieved stable disease (SD) for > or =24 weeks, including two patients with SD
      for 2 years and one with SD for 14 months. Fulvestrant was well tolerated with
      the majority of adverse events related to the site of metastatic disease. These
      data demonstrate that fulvestrant is a well tolerated and effective endocrine
      therapy for postmenopausal women with metastatic breast cancer who have been
      heavily pretreated with prior therapies. The novel mechanism of action of
      fulvestrant reduces the likelihood of cross-resistance with other endocrine
      therapies and therefore this agent may be active in patients who have proved to
      be resistant to treatments such as tamoxifen or AIs. The use of fulvestrant
      earlier in the sequence of endocrine treatments may achieve better responses than
      observed in this heavily pretreated patient population.

PMID- 15564794
TI  - Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in
      situ (DCIS) is an early event in breast tumorigenesis.
AB  - Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in
      a subset of invasive breast cancers. FAK transmits signals that mediate several
      functions including tumor cell proliferation, migration, adhesion and survival.
      We used immunohistochemical techniques to assess FAK expression in patients with
      fibrocystic disease (FCD), atypical ductal hyperplasia (ADH), ductal carcinoma in
      situ (DCIS) and infiltrating ductal carcinoma (IDC). Formalin-fixed, paraffin
      embedded (FFPE) tissue sections were obtained from 119 patients (12 FCD, 38 ADH,
      51 DCIS and 18 IDC). The anti-FAK 4.47 monoclonal antibody was used to detect FAK
      expression. FAK expression was scored as high (3 or 4 intensity and > or =90%
      positive cells) or low. The DCIS tissue sections demonstrated high FAK expression
      in 34/51 (66%) of the sections. High FAK expression was demonstrated in 6/18
      (33%) of the IDC tissue sections and 8/38 (21%) of the ADH tissue sections. None
      (0/12) of the FCD tissues sections stained high for FAK. The pattern of FAK
      expression in DCIS was significantly higher than ADH (p < 0.0001) and IDC (p =
      0.02). We conclude that FAK overexpression in preinvasive, DCIS tumors precedes
      tumor cell invasion or metastasis, suggesting that FAK may function as a survival
      signal and be an early event in breast tumorigenesis.

PMID- 15564795
TI  - Efficacy and safety of single agent capecitabine in pretreated metastatic breast
      cancer patients from the French compassionate use program.
AB  - BACKGROUND: A retrospective source review identifying predictive factors and
      assessing safety and efficacy in pretreated metastatic breast cancer (MBC)
      patients treated with capecitabine in a French compassionate-use program.
      PATIENTS AND METHODS: 197 patients received capecitabine at an initial total dose
      0.25-3.0 g/m2/day, twice daily for 14 consecutive days, every 3 weeks. RESULTS:
      Median patient age was 56 years (range, 31-88), 19% had performance status (PS) 3
      4. Prior palliative and adjuvant treatment was reported in 96 and 61% of patients
      respectively. Best overall response rate (ORR) was 15% (95% confidence interval
      [CI], 11-21%) and 49% had benefit (CR, PR or SD). Median time to progression
      (TTP) and overall survival were 4.8 and 14.7 months, respectively. Median TTP in
      responders was 8.9 months (95%CI 6.1-11.7). Grade 3/4 neutropenia and grade 3
      thrombocytopenia occurred in 8 and 3% of patients respectively. Hand-foot
      syndrome (grade 3/4 in 16% of patients), diarrhea, stomatitis and asthenia were
      prevalent. Multivariate analysis showed ORR was significantly influenced by PS >
      or = 2 (p = 0.004), time from metastases diagnosis to capecitabine treatment (p =
      0.015) and presence of liver metastases at inclusion (p = 0.047). Abnormal liver
      function tests at baseline were associated with severe thrombocytopenia and
      anemia. Four treatment-related deaths occurred. CONCLUSION: Capecitabine is
      active in heavily pretreated MBC patients and has a favorable toxicity profile
      with the added advantage of being an oral drug administered in an outpatient
      setting.

PMID- 15564796
TI  - Genomic patterns of allelic imbalance in disease free tissue adjacent to primary
      breast carcinomas.
AB  - Mammary stroma plays an important role in facilitating the neoplastic
      transformation of epithelial cells, modulating integrity of the extracellular
      matrix, and maintaining genomic stability, but molecular mechanisms by which
      stroma affects epithelial structure and function are not well-defined. We used
      laser-assisted microdissection of paraffin-embedded breast tissues from 30
      patients with breast disease and a panel of 52 microsatellite markers defining 26
      chromosomal regions to characterize genomic patterns of allelic imbalance (AI) in
      disease-free tissue adjacent to sites of breast disease and to define genomic
      regions that may contain genes associated with early carcinogenic processes. The
      mean frequency of AI in histologically normal tissue adjacent to the primary
      carcinomas (15.4%) was significantly higher than that in distant tissue from the
      same breast (3.7%). The pattern of AI across all chromosomal regions differed
      between the adjacent tissue and primary tumor in every case. Unique AI events,
      observed only in tumor (15% of informative markers) or only in adjacent cells
      (10% of informative markers), were far more common than AI events shared between
      tumor and adjacent cells (approximately 4%). Levels of AI characteristic of
      advanced invasive carcinomas were already present in non-invasive ductal
      carcinomas in situ, and appreciable levels of AI were observed in adjacent non
      neoplastic tissue at all pathological stages. Chromosome 11p15.1 showed
      significantly higher levels of AI in adjacent cells (p < 0.01), suggesting that
      this region may harbor genes involved in breast cancer development and
      progression. Our data indicate that genomic instability may be inherently greater
      in disease-free tissue close to developing tumors, which may have important
      implications for defining surgical margins and predicting recurrence.

PMID- 15564797
TI  - Synergistic effect of a retinoid X receptor-selective ligand bexarotene (LGD1069,
      Targretin) and paclitaxel (Taxol) in mammary carcinoma.
AB  - We have previously shown that the retinoid X receptor (RXR) ligand bexarotene
      (LGD1069, Targretin) is efficacious as a chemopreventive and chemotherapeutic
      agent in rat N-nitroso-N-methylurea (NMU)-induced mammary carcinomas (Cancer Res
      58: 479-484, 1998). To determine additional role for bexarotene in breast cancer
      treatment, we evaluated the effect of bexarotene on the efficacy of paclitaxel
      (Taxol) treatment in a rat NMU-derived mammary tumor cell line, NMU-417, in vitro
      and in rat NMU-induced mammary tumors in vivo. Our growth inhibition results
      showed that the bexarotene/paclitaxel combination produced a concentration
      dependent synergy in NMU-417 tumor cell line. Synergistic growth inhibition by
      the combination was associated with an increase in cell death induced by both
      agents. In rat NMU-induced mammary tumor model in vivo, the benefit of
      combination therapy was observed as early as 1 week after treatment and increased
      as treatment continued. At the end of 6 weeks of treatment, the
      bexarotene/paclitaxel combination produced an overall objective response rate of
      94% compared with a rate of 12% in paclitaxel-treated and 58% in bexarotene
      treated animals, an effect that was more than the additive effects produced by
      single agents. Although both bexarotene alone and the bexarotene/paclitaxel
      combination reduced tumor multiplicity to similar extent, the combination regimen
      produced a statistically significant decrease in total tumor burden compared to
      single agents and untreated controls (two-tailed, p < 0.05). Combination therapy
      did not further alter body weight nor increase toxicity when compared to single
      agents. In summary, our results demonstrated the potential of using a RXR
      selective ligand in combination with chemotherapy for the treatment of breast
      cancer.

PMID- 15564798
TI  - Distinct incidence patterns among in situ and invasive breast carcinomas,with
      possible etiologic implications.
AB  - BACKGROUND: Incidence patterns are well-established for invasive breast carcinoma
      (InvBC) overall and for InvBC defined by estrogen receptor (ER) expression, but
      are not as well-defined for breast carcinoma in situ (CIS). METHODS: We,
      therefore, examined and compared the incidence patterns for CIS and InvBC in the
      SEER program to define these patterns and to generate etiologic hypotheses. Data
      were stratified by age < 50 and > or =50 years to approximate menopause. RESULTS:
      During the years 1973-2000, annual age-adjusted incidence rates rose 660% for CIS
      and 36% for InvBC, with the most rapid increases occurring in women age > or =50
      years. Age-specific incidence rate curves for CIS increased until age 50 years,
      and then flattened, irrespective of ER expression. On the other hand, rates for
      InvBC overall and for InvBC defined by ER-positive expression increased
      continuously with aging, whereas rates for InvBC defined by ER-negative
      expression flattened after 50 years. Age frequency distribution for CIS and for
      ER-negative InvBC demonstrated bimodal populations, with a predominant early
      onset peak incidence at age 50 years. Age frequency distribution for ER-positive
      InvBC showed bimodal populations with a predominant late-onset mode at age 71
      years. CONCLUSION: Over the last three decades, age-adjusted incidence trends
      differed for CIS and InvBC in the United States, possibly due to screening
      mammography and/or etiologic diversity. Indeed, age-specific incidence patterns
      suggested that carcinogenic events operating early in reproductive life had
      greater impact upon CIS and InvBC defined by ER-negative expression than upon
      InvBC overall and InvBC defined by ER-positive expression.

PMID- 15564799
TI  - Racial disparities in female breast cancer in South Carolina: clinical evidence
      for a biological basis.
AB  - OBJECTIVE: Racial disparities in breast cancer outcomes are well documented:
      African-American (AA) women have markedly poorer survival than do European
      American (EA) women. A growing literature suggests that AA women have, on
      average, tumors of more aggressive histopathology, even if discovered early. We
      investigated this in our South Carolina population. METHODS: Tumor registry data
      for 1687 AA and EA women with breast cancers newly diagnosed during 2000-2002 at
      the two Palmetto Health hospitals in Columbia, SC, were reviewed. RESULTS:
      Corresponding to our regional population, 31% of cancers were in AA women. In
      both racial groups, 19% were in situ. Among women with invasive cancers, AA women
      had significantly earlier age at diagnosis than did EA women. Fewer AA women had
      lobular carcinoma (p = 0.001) or Her-2 over-expressing disease (7 versus 19%, p =
      0.001). Significantly more AA women had high-grade cancer, larger tumors,
      axillary metastases and ER negative/PR negative tumors. After controlling for T
      stage, AA women were significantly more likely to have high-grade and/or ER
      negative disease. Detection of invasive cancers by screening mammogram was less
      frequent in AA women (40 versus 53%, p < 0.000), and in small ER negative
      cancers. CONCLUSIONS: At diagnosis, breast cancers in AA women tend to have the
      hallmarks of more aggressive and less treatable disease, even in small tumors, a
      pattern resembling that of breast cancers in younger EA women. Whatever the
      causes, these observations suggest breast cancer is biologically different in AA
      women. This may contribute substantially to the poorer outcomes in African
      American women.

PMID- 15564800
TI  - Novel germline mutations in breast cancer susceptibility genes BRCA1, BRCA2 and
      p53 gene in breast cancer patients from India.
AB  - Mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 account for more
      than 80% of hereditary breast and ovarian cancers. p53 tumor suppressor gene that
      controls cellular growth and differentiation is also known to be mutated in more
      than 50% of human cancers including breast cancer. We have carried out a study on
      BRCA1 and BRCA2 along with p53 gene mutations in both sporadic as well as
      familial breast cancer patients from India where breast cancer is fast emerging
      as a major cancer among premenopausal urban women. We examined 124 untreated
      primary breast cancer patients comprising 100 sporadic and 24 familial cases
      including 56 age-matched healthy controls for the presence of BRCA1, BRCA2 and
      the p53 gene mutations using PCR-SSCP and direct nucleotide sequencing. Certain
      frequently mutated exons such as 2, 5, 11, 13 and 20 of BRCA1, exons 2, 9, 11
      (for 6174delT), 18 and 20 of BRCA2 and 4-9 exons of p53 gene were analyzed in
      sporadic breast cancer while all 22 coding exons of BRCA1 including its flanking
      intronic regions along with above mentioned exons of BRCA2 and p53 gene were
      analyzed in familial breast cancer patients. We identified six patients (25%)
      with BRCA1 mutation of which three were found to be of novel type one in exon 16
      (4956insG) and two in exon 7 (Lys110Thr) (Ser114Pro) out of 24 familial breast
      cancer patients studied from two different geographic regions/populations of
      India. Two sisters from a single family (12.5%) out of eight families from Goa
      with Portuguese colonial origin showed presence of founder Ashkenazi Jewish BRCA1
      mutation (185delAG) along with (IVS7 561-34T>C; IVS18 5271 + 66G > A). While from
      New Delhi, four (25%) of 16 breast cancer families showed BRCA1 mutations; a
      frame shift protein truncating (4956insG), a transition nonsense (Gln1395Stop)
      and two amino acid substitutions (Lys110Thr) and (Ser114Pro). Only one (4%) p53
      mutation (Val97Ile) in its exon 4 along with BRCA1 mutation (4956insG) could be
      detected. No major sequence variation in BRCA2 gene was observed except for G203A
      at 5' UTR of exon 2, a common population polymorphism in two Goan patients who
      also showed silent nucleotide change for amino acid serine at codon 1436 of BRCA1
      gene. None of the 100 sporadic breast cancer patients revealed any protein
      truncating or deleterious BRCA1 or BRCA2 gene mutation. Interestingly, three (3%)
      p53 mutations in its exon 5 were detected in sporadic breast cancer patients.
      Although three novel BRCA1 mutations including a founder Ashkenazi Jewish BRCA1
      mutation were recorded in Indian women with familial breast cancer, the overall
      prevalence of BRCA gene mutations in Indian women with a family history of breast
      cancer appears to be low.

PMID- 15564801
TI  - A population-based study of the impact of delaying radiotherapy after
      conservative surgery for breast cancer.
AB  - BACKGROUND: Practice guidelines have set a maximum waiting time to radiation
      therapy for breast cancer. We evaluated if delaying radiotherapy resulted in
      worse outcomes in a large cohort of women with node-negative breast cancer.
      METHODS: We selected a random sample of cases among women diagnosed with
      localized breast cancer in five regions of Quebec, Canada, between 1988 and 1994.
      Only women with pathologically (n = 926) or clinically (n = 136) negative
      axillary nodes, and stage 1 or 2 disease treated with conservative surgery and
      radiotherapy were eligible. Information was obtained by chart review, queries to
      physicians and linkage with administrative databases. Outcomes were estimated by
      Kaplan-Meier method and Cox proportional hazards analysis. Median follow-up was
      7.1 years (range: 0.9-11.8). RESULTS: Median delay to radiotherapy was 12.4 weeks
      in those who received chemotherapy and 8.4 weeks in others. Overall survival at 7
      years was 85.6%. Local relapse-free and distant disease-free survivals were 77.6
      and 76.2%. There was no significant difference in survival according to delay to
      radiotherapy in crude or multivariate analysis adjusting for several prognostic
      factors, including systemic treatment. The risk of local failure conditional on
      survival in women who received radiotherapy more than 12 weeks after surgery was
      increased (hazard ratio: 1.75, 95% confidence interval: 1.00, 3.08, p-value =
      0.052). CONCLUSIONS: Although longer waiting time to radiotherapy may compromise
      local control, it does not influence survival at 7 years when other predictors of
      outcomes are taken into account. Well controlled studies are needed to confirm
      and better characterize this relationship.

PMID- 15564802
TI  - [Proteomic approach in gastrointestinal and liver research].
AB  - In the post-genomic era, the focus of research is now moving to functional
      genomics employing the information on predicted gene products provided by genome
      sequencing. Proteomics, the global analysis of structures, functions, and
      interactions of whole cellular proteins, draws the special attention as a tool
      for documenting the disease pathogenesis or progression. The high-throughput
      technology has become feasible by considerable improvement of two dimensional
      electrophoresis and mass fingerprinting. Thus proteome techniques can be used as
      tools to study the disease processes, develop new biomakers for diagnosis and
      early detection of diseases, and accelerate drug development. In this review, we
      discuss the background and techniques of proteomics, and potential applications
      to the research of gastrointestinal diseases.

PMID- 15564803
TI  - [Importance of age and other risk factors in NSAID-induced gastropathy].
AB  - BACKGROUND/AIMS: It is clinically important to analyze the risk factors of NSAID
      induced gastropathy because there could be no symptoms. Age is the most important
      risk factor according to previous reports. The aim of this study was to find risk
      factors of NSAID-induced gastropathy and to confirm the association between NSAID
      induced gastropathy and age. METHODS: We retrospectively assessed 300 patients
      who conducted an upper gastroscopy during the course of chronic NSAID treatment.
      RESULTS: Median age of patients group is 51.4 +/- 12.2 years. In multivariate
      analysis, age and ulcer history are two significant risk factors. Median age is
      46.7 +/- 10.7 years for the patients with nonspecific gastroscopic finding, 53.0
      +/- 12.5 for those with erosion, 57.6 +/- 10.0 for those with ulcer, and 63.2 +/-
      8.9 for those with hemorrhage. The proportion of ulcer patients is as follows: 6%
      in the patients of under 40 years old, 14.9% in patients of the 40s, 20% in
      patients of the 50s, 30.9% in patients of the 60s, 33.3% in patients over 70
      years. The proportion of nonspecific findings is 62.2% in patients of the 40s,
      37.8% in patients of the 50s, and 29% in patients over 60 years. CONCLUSIONS: Age
      is the most important risk factor of the NSAID-induced gastrointestinal mucosal
      injury. A larger randomized prospective control study will be required in the
      future for more conclusive results.

PMID- 15564804
TI  - [Effect of glutamine on the non-steroidal anti-inflammatory drug-induced
      bacterial translocation].
AB  - BACKGROUND/AIMS: NSAIDs induce gut damage throughout the entire gastrointestinal
      tract and bacterial translocation. The aim of this study was to examine if
      administration of glutamine was able to prevent the NSAID-induced gut damages and
      bacterial translocation in the animal models. METHODS: Rats were utilized into 5
      groups; control group, diclofenac group, and diclofenac with glutamine 0.8, 1.6,
      and 3.2 g/kg/day group. The animals with glutamine were fed with L-glutamine for
      4 days before diclofenac administration. Gut injury was induced by administration
      of a single dose of diclofenac (80 mg/kg orally). Intestinal permeability (24
      hour urinary excretion of phenolsulfonphthalein), enteric aerobic bacterial
      counts, serum biochemical profiles and bacterial translocation to mesenteric
      lymph nodes, liver and spleen were measured. RESULTS: Diclofenac caused the
      increase in intestinal permeability, enteric bacterial count, enteric protein and
      albumin loss and bacterial translocation. Administration of glutamine reduced the
      increase in intestinal permeability, protein losing enteropathy, enteric
      bacterial overgrowth and bacterial translocation induced by diclofenac.
      CONCLUSIONS: Glutamine may have beneficial effects on NSAID-induced gut damage
      and bacterial translocation.

PMID- 15564805
TI  - [Effect of infliximab in the treatment of refractory inflammatory bowel disease
      with complication].
AB  - BACKGROUND/AIMS: Many studies on infliximab have confirmed its efficacy in the
      remission induction and even maintenance in refractory and fistulizing Crohn's
      disease. We report the treatment efficacy of infliximab in Crohn's disease and
      ulcerative colitis refractory to steroid treatment and the complications of
      infliximab treatment. METHODS: We performed infliximab administration in 5 cases
      (3 Crohn's disease, 2 ulcerative colitis) refractory to systemic steroid
      treatment and 5 cases of Crohn's disease with fistula. Patients received an
      intravenous infusion of infliximab at 3-5 mg/kg body weight. RESULTS: In 3 cases
      of refractory Crohn's patients, clinical response and remission induction were
      obtained in 2 (67%) and 1 cases (33%). After infusion of infliximab, the
      occlusion of internal fistula could be found in all 2 cases. Two out of 3 cases
      of anal fistula were completely healed. In two cases of refractory ulcerative
      colitis, one case who showed clinical manifestation of toxic megacolon had
      improved and avoided the colectomy, but the other case did not respond to the
      infusion of infliximab and underwent colon resection. CONCLUSIONS: We found that
      administration of infliximab is an effective alternative for refractory and
      fistulizing Crohn's disease but further studies are necessary for refractory
      ulcerative colitis.

PMID- 15564806
TI  - [Clinical characteristics of patients with chronic constipation after radical
      hysterectomy or delivery].
AB  - BACKGROUND/AIMS: This study was aimed to analyze the clinical characteristics of
      patients who developed constipation after radical hysterectomy or delivery and to
      investigate the results of biofeedback therapy for these patients. METHODS:
      Thirty-five chronic constipation patients with radical hysterectomy (radical
      hysterectomy group), 27 chronic constipation patients with delivery (delivery
      group) and 27 constipation patients with no history of hysterectomy or delivery
      (control group) were included. Clinical characteristics of these patients,
      including the results of biofeedback therapy, were analyzed. RESULTS: The
      delivery group showed higher rates of pelvic floor dyssynergia than the control
      group (14/27, 52% vs. 6/27, 22%; p<0.05). The prevalence of slow transit
      constipation was lower in the radical hysterectomy group and delivery group than
      in the control group (7/35, 20% and 5/27, 19% vs. 12/27, 44%; p<0.05). The
      prevalence of anatomical abnormalities was not different between the groups. The
      radical hysterectomy group showed higher rate of obstructive sensation and the
      delivery group showed higher rate of hard stool and digital maneuvers. The
      biofeedback therapy was effective in 10 out of 12 patients (91%) among the
      radical hysterectomy and delivery group. CONCLUSIONS: Radical hysterectomy and
      delivery seem to induce functional constipation, which may be caused by anorectal
      dysfunction such as pelvic floor dyssynergia. The biofeedback treatment was
      effective in functional constipation after radical hysterectomy or delivery.

PMID- 15564807
TI  - [Should small bowel diverticula be removed?].
AB  - BACKGROUND/AIMS: Small bowel diverticulum is a rare disease that can be found
      incidentally during a surgical operation. Since reported complication rate is
      low, uncomplicated small bowel diverticula are generally recommended to be
      untreated. The aim of this study was to elucidate clinical features of this
      disease and to determine whether incidental small bowel diverticula should be
      removed for cure. METHODS: We reviewed the medical records of 80 patients with
      small bowel diverticular disease who underwent operation at Asan Medical Center
      between July 1989 and March 2003, retrospectively. RESULTS: Male to female ratio
      was 61:19, and the mean age was 44 (0-91) years. The most common diverticulum of
      small bowel is Meckel's diverticulum (63.8%), followed by duodenal diverticulum
      (15%), jejunal diverticulum (12.5%), and ileal diverticulum (8.7%). Of the 80
      cases, 43 (53.7%) were symptomatic, and 37 (46.3%) were incidental. In the
      symptomatic patients, the most frequent symptom was abdominal pain (58.1%),
      followed by bleeding (44.2%). As for the treatments, segmental resection (53.7%)
      was performed more commonly than diverticulectomy (43.8%) in the symptomatic
      patients. Postoperative complications occurred more commonly in the symptomatic
      patients (25.6%) than the incidental patients (8.1%). Duodenal diverticula had a
      high morbidity and mortality rate. CONCLUSIONS: We should consider the
      diverticular disease of small bowel in patients with unexplained abdominal pain
      or gastrointestinal bleeding. As most small bowel diverticula, except for
      duodenal diverticula, are found incidentally and easily removed without
      postoperative morbidity or mortality, surgical resection appears to be
      recommended for the purpose of accurate diagnosis and treatment.

PMID- 15564808
TI  - [Comparison of survival of advanced hilar cholangiocarcinoma after biliary
      drainage alone versus photodynamic therapy with external drainage].
AB  - BACKGROUND/AIMS: Photodynamic therapy (PDT) has a promising effect on non
      resectable hilar cholangiocarcinoma. The aim of this study was to compare overall
      survival of PDT plus biliary drainage versus biliary stent alone in advanced
      hilar cholangiocarcinoma. METHODS: Twenty patients who were treated with
      endoscopic biliary drainage alone (Group A) and 27 patients treated with PDT
      under percutaneous cholangioscopy and additional percutaneous biliary drainage
      (Group B) were analyzed retrospectively. RESULTS: The mean bilirubin level
      declined effectively in both group after treatment. One-year survival was 28% in
      group A, 52% in group B (p<0.05). Median survival time was 288 days in group A,
      558 days in group B (p=0.0143). CONCLUSIONS: PDT under percutaneous
      cholangioscopy seems to be more effective in extending survival than biliary
      drainage alone in advanced hilar tumor. To investigate whether PDT can increase
      survival rates, further prospective, randomized study is needed.

PMID- 15564809
TI  - [A case of the ruptured splenic artery aneurysm treated with transcatheter
      embolization].
AB  - Splenic artery aneurysms are the most common visceral artery aneurysms, which are
      usually found incidentally. The most common complication of splenic artery
      aneurysms is spontaneous rupture into the peritoneal cavity, which leads to acute
      peritonitis and shock. Less commonly, it may rupture directly into the stomach,
      small bowel or pancreatic duct and may present with acute gastrointestinal
      hemorrhage. We report a rare case of the ruptured splenic artery aneurysm,
      presenting as acute massive hematochezia which was treated with transcatheter
      embolization.

PMID- 15564810
TI  - [A case of non-traumatic hemobilia due to warfarin therapy].
AB  - Hemobilia is a hemorrhage into the biliary tract that may follow surgical trauma,
      liver biopsy, aneurysms, extra- or intra-hepatic tumors of the biliary tract,
      gallstones, and inflammatory lesion of liver, especially helminthic or pyogenic.
      Sometimes, it is associated with primary liver cancer. An 84 year-old woman was
      admitted because of continuous right upper quadrant pain 4 days before admission.
      Physical examination revealed decreased skin turgor, icteric sclerae and severe
      tenderness on right upper quadrant abdomen. She had no hepatosplenomegaly, and no
      rebound tenderness. She has been taking warfarin for 3 weeks before admission
      because of atrial fibrillation. On admission, serum bilirubin and transaminase
      were elevated. The level of hemoglobin and hematocrit were 11.3 g/dL and 37.4%,
      respectively. HBsAg was negative, but IgG anti-HBc and anti-HBs were positive and
      anti-HCV was negative. Parasite skin test and stool ova count demonstrated non
      specific findings. Stool occult blood was strongly positive, and prothrombin time
      was markedly prolonged. According to endoscopic retrograde
      cholangiopancreatography, common bile duct was dilated, and filled with blood
      clot but there was no stone in bile tree. After two weeks, serum transaminase,
      bilirubin, hemoglobin, hematocrit, and CA19-9 were normalized. We report a case
      of hemobilia, occurring in a patient with continuous warfarin use.

PMID- 15564811
TI  - [Extraintestinal tuberculosis is useful for differential diagnosis of intestinal
      tuberculosis].

PMID- 15564813
TI  - Aripiprazole and atypical neuroleptic malignant syndrome.

PMID- 15564814
TI  - Risperidone and pancreatitis.

PMID- 15564815
TI  - Links between pubertal timing and neighborhood contexts: implications for girls'
      violent behavior.
AB  - OBJECTIVE: To investigate links between girls' violent behavior, pubertal timing,
      and neighborhood characteristics. METHOD: A total of 501 Hispanic, black, and
      white adolescent girls and their parents were interviewed twice over a 3-year
      period (1995-1998). Violent behavior was assessed using the Self-Report of
      Offending Scale and pubertal timing was measured via menarche. This probability
      sample was drawn from Chicago. To characterize neighborhoods, neighborhood
      clusters were created. U.S. Census data were mapped onto each neighborhood
      cluster to represent levels of concentrated disadvantage, immigrant
      concentration, and residential mobility. The response rate was approximately 70%.
      RESULTS: More than 25% of girls engaged in violent behavior at the second
      interview. Controlling for demographic indicators, previous violence, and other
      psychological factors, no differences were found in violent behavior as a
      function of menarcheal timing or neighborhood characteristics. Instead, results
      revealed that early maturers engaged in violent behavior only if they lived in
      neighborhoods characterized by high concentrated disadvantage. Early maturers in
      neighborhoods characterized by high concentrated disadvantaged engaged in three
      times the number of violent acts as early maturers in less disadvantaged
      neighborhoods. Depressive symptoms and previous violent behavior were also
      associated with girls' subsequent violent behavior. CONCLUSIONS: Results
      indicated that girls who experience a double vulnerability--early maturation and
      neighborhoods of disadvantage--are susceptible to engaging in violent behavior.
      This suggests the need for clinical evaluation to examine the implications of
      pubertal timing and the context of girls' behavior.

PMID- 15564816
TI  - Cognitive-behavioral therapy for depression in adolescents with inflammatory
      bowel disease: a pilot study.
AB  - OBJECTIVE: To evaluate the safety and feasibility of cognitive-behavioral therapy
      (CBT) for depression in physically ill adolescents. METHOD: In an open trial, 11
      adolescents (12-17 years) with inflammatory bowel disease and either major or
      minor depression underwent 12 sessions of a manual-based CBT enhanced by social
      skills, physical illness narrative, and family psychoeducation components.
      Standardized instruments assessed pre- to posttreatment changes in depression,
      physical health, global psychological functioning, and social functioning.
      Perceived helpfulness and satisfaction with CBT were assessed. RESULTS: There
      were significant reductions in DSM-IV depression diagnoses and depressive
      symptoms and improvements in global psychological and social functioning.
      Adolescents' perceptions of their general health and physical functioning
      improved, although illness severity measures were unchanged. High subject
      satisfaction and helpfulness ratings for CBT were found along with no adverse
      events and high subject adherence. CONCLUSIONS: A manual-based CBT approach
      adapted to treat depression in physically ill adolescents appears to be a safe,
      feasible, and promising intervention.

PMID- 15564817
TI  - Reducing aggressive behavior in boys with a social cognitive group treatment:
      results of a randomized, controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a social cognitive intervention
      program for Dutch aggressive boys and to compare it with a social skills training
      and a waitlist control group. METHOD: A randomized, controlled treatment outcome
      study with 97 aggressive boys (aged 9-13 years) was presented. An 11-session
      group treatment, a social cognitive intervention program (n = 42) based on
      Dodge's social information-processing theory, was compared with social skills
      training (n = 40) and waitlist control group (n = 15). Measures of aggressive
      behavior, self-control, social cognitive skills, and appropriate social behavior
      were completed before and after the group treatment and at 1-year follow-up.
      RESULTS: The outcome of both treatment conditions indicated (1) a significant
      increase in appropriate social behavior, social cognitive skills, and self
      control and (2) a significant decrease in aggressive behavior. There was a
      significant difference between treatment and no treatment and between the social
      cognitive intervention program and social skills training on various child,
      parent, and teacher measures. CONCLUSIONS: The expectation that focusing on the
      deficits and distortions in social cognitive processes (social cognitive
      intervention program) instead of merely focusing on social skills (social skills
      training) would enhance the effectiveness was supported on child, parent, and
      teacher measures. At 1-year follow-up, the mean effect sizes of the social
      cognitive intervention program and social skills training were 0.76 and 0.56,
      respectively.

PMID- 15564818
TI  - Comparison of increasingly detailed elicitation methods for the assessment of
      adverse events in pediatric psychopharmacology.
AB  - OBJECTIVE: To improve the gathering of adverse events (AEs) in pediatric
      psychopharmacology by examining the value and acceptability of increasingly
      detailed elicitation methods. METHOD: Trained clinicians administered the Safety
      Monitoring Uniform Report Form (SMURF) to 59 parents and outpatients (mean age +/
      SD = 11.9 +/- 3.2 years) in treatment, with 36% on stimulants, 29% on selective
      serotonin reuptake inhibitor drugs, 10% on both, and 25% on other drug
      combinations. The SMURF included a brief general inquiry, a drug-specific
      inquiry, and a comprehensive body system review (BSR). RESULTS: SMURF
      administration took 24.6 +/- 13.9 minutes (median, 21). The BSR took 15.5 +/- 8.1
      minutes (median, 14) longer (p < .0001) than the general inquiry (4.3 +/- 5.4
      minutes) and the drug-specific inquiry (4.2 +/- 2.9 minutes). The general inquiry
      elicited 48 AEs, the drug-specific inquiry elicited 16 additional AEs, and the
      BSR 129 additional AEs. Of all the clinically relevant AEs elicited by the SMURF
      (n = 36), 19 (53%) were elicited by the BSR. The BSR length and detail were
      acceptable to parents but not to clinicians. CONCLUSIONS: The BSR elicited
      additional clinically significant AEs that had been missed with less detailed
      methods. Parents, but not clinicians, rated satisfaction and acceptability of the
      BSR as good.

PMID- 15564819
TI  - Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents.
AB  - OBJECTIVE: To determine the pharmacokinetics of fluvoxamine in children and
      adolescents and to compare pharmacokinetic data from adolescents to adults from a
      previous study. METHOD: Fluvoxamine was titrated to a target dose of 100 mg
      b.i.d. in children (6-11 years) and 150 mg b.i.d. in adolescents (12-17 years)
      with obsessive-compulsive disorder or other disorder requiring fluvoxamine
      treatment. Serum samples were collected over 12 hours after 12 or more
      consecutive doses of 25, 50, 100, and 150 mg. RESULTS: Sixteen children (seven
      females, nine males) and 18 adolescents (nine females, nine males) were included
      in the pharmacokinetic analyses. Children demonstrated higher mean peak plasma
      concentration, higher mean area under the plasma concentration-time curve, and
      lower apparent oral clearance compared with adolescents. Compared with male
      children, female children had higher mean area under the plasma concentration
      time curve, higher mean peak plasma concentration, and more reports of adverse
      events. However, the area under the plasma concentration-time curve was not
      directly correlated with frequency or severity of adverse events.
      Pharmacokinetics were nonlinear over the dose range studied. No pharmacokinetic
      differences were apparent between adolescents and adults on 150 mg b.i.d.
      CONCLUSIONS: These pharmacokinetic results suggest that children (especially
      females) have a higher exposure to fluvoxamine than adolescents, whereas
      adolescents and adults appear to have similar exposure to fluvoxamine.

PMID- 15564820
TI  - Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian
      multigenerational families.
AB  - OBJECTIVE: Eighteen extended multigenerational families were recruited from the
      genetically isolated Paisa community in Colombia to conduct genetic studies of
      attention-deficit/hyperactivity disorder (ADHD). This report describes the
      inclusion strategy and clinical features of participants to facilitate
      comparisons with other data sets. METHOD: Families were selected through a fixed
      sampling scheme beginning with child probands referred for clinical evaluation
      for ADHD. Direct structured psychiatric interviews were conducted with 433
      informative individuals, including 92 children aged 4 to 11, 57 adolescents aged
      12 to 17, and 284 adults. Best estimate ADHD diagnoses were established for each
      informative pedigree member. RESULTS: These families contained a high proportion
      of individuals affected with ADHD (32.8%), which was highly comorbid with conduct
      disorder (50%; odds ratio 11.5, 95% confidence interval = 6.4-20.9), oppositional
      defiant disorder (25.4%; odds ratio 2.7, confidence interval = 1.5-4.8), and
      associated conditions including nicotine dependence and alcohol abuse and/or
      dependence. CONCLUSIONS: ADHD in these extended Paisa families is highly comorbid
      with conduct and oppositional defiant disorders. This pattern of comorbidity, as
      well as the large dense pedigrees of the sample, suggests that it will be
      particularly useful for molecular genetic studies that are currently under way.

PMID- 15564821
TI  - Practice parameter for use of electroconvulsive therapy with adolescents.
AB  - Electroconvulsive therapy (ECT) may be an effective treatment for adolescents
      with severe mood disorders and other Axis I psychiatric disorders when more
      conservative treatments have been unsuccessful. ECT may be considered when there
      is a lack of response to two or more trials of pharmacotherapy or when the
      severity of symptoms precludes waiting for a response to pharmacological
      treatment. The literature on ECT in adolescents, including studies and case
      reports, was reviewed and then integrated into clinically relevant guidelines for
      practitioners. Mood disorders have a high rate of response to ECT (75%-100%),
      whereas psychotic disorders have a lower response rate (50%-60%). Consent of the
      adolescent's legal guardian is mandatory, and the patient's consent or assent
      should be obtained. State legal guidelines and institutional guidelines must be
      followed. ECT techniques associated with the fewest adverse effects and greatest
      efficacy should be used. The presence of comorbid psychiatric disorder is not a
      contraindication. Systematic pretreatment and posttreatment evaluation, including
      symptom and cognitive assessment, is recommended.

PMID- 15564822
TI  - Practice parameter for the assessment and treatment of children and adolescents
      with enuresis.
AB  - Enuresis is a symptom that is frequently encountered in child psychiatric
      evaluations. Careful assessment is required to identify specific urologic,
      developmental, psychosocial, and sleep-related etiologies. For most children with
      enuresis, however, a specific etiology cannot be determined. Treatment then
      involves supportive approaches, conditioning with a urine alarm, or medications-
      imipramine or desmopressin acetate. The psychosocial consequences of the symptom
      must be recognized and addressed with sensitivity during the evaluation and
      treatment of enuresis.

PMID- 15564824
TI  - Dominant negative p63 isoform expression in head and neck squamous cell
      carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: p63, a member of the p53 family of genes, is vital for
      normal epithelial development and may play a critical role in epithelial tumor
      formation. Although p63 has been identified in various head and neck
      malignancies, a detailed analysis of which of the six isoforms of the p63 gene is
      present in normal mucosa and head and neck malignancies has not yet been
      performed. The study analyzed p63 isoform expression on the RNA and protein level
      in normal, diseased, and malignant mucosa of the head and neck to examine the
      differential expression of p63 isoforms in head and neck tumors versus adjacent
      nonmalignant tissue and to identify the predominant p63 isoform expressed in head
      and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Three experiments were
      performed. In experiment 1, p63 expression was analyzed by immunohistochemical
      analysis in 36 HNSCC specimens and matched normal tissue control specimens
      harvested from the same patient. Western blot analysis was also performed on
      matched specimens to confirm the identity of the p63 isoforms that were found. In
      experiment 2, reverse transcriptase polymerase chain reaction (RT-PCR) analysis
      was performed on matched normal and tumor specimens to analyze and quantitatively
      compare p63 isoform expression at the RNA level. In experiment 3, p63 expression
      was evaluated by immunohistochemical analysis in oral lichen planus, a benign
      mucosal lesion marked by hyperdifferentiation and apoptosis. METHODS:
      Immunohistochemical analysis, RT-PCR, and Western blot analysis of p63 were
      performed on HNSCC specimens and matched normal tissue control specimens. p63
      expression in oral lichen planus specimens was also examined by
      immunohistochemical analysis. RESULTS: In experiment 1, analysis of 36 HNSCC
      specimens from various head and neck subsites showed p63 expression in all tumors
      and matched normal tissue specimens (36 of 36). Western blot analyses indicated
      that dominant negative (DeltaN) isoform p63alpha (DeltaNp63alpha) is the major
      isoform expressed at the protein level in tumors and adjacent normal tissue. In
      experiment 2, RT-PCR analyses of 10 matched specimens confirmed that, although
      all three DeltaNp63 isoforms (DeltaNp63alpha, DeltaNp63beta, and DeltaNp63gamma)
      are expressed in normal and malignant mucosa of the head and neck, DeltaNp63alpha
      is the predominant transcript expressed. In experiment 3, immunohistochemical
      analysis of p63 in the pro-apoptotic condition of lichen planus indicated that
      p63 is underexpressed as compared with normal mucosal specimens. CONCLUSION:
      Although all three DeltaNp63 isoforms are present in HNSCC, DeltaNp63alpha
      protein is the predominant isoform expressed in these malignancies.
      DeltaNp63alpha is also overexpressed in tumors compared with matched normal
      tissue specimens and is underexpressed in the pro-apoptotic condition of lichen
      planus. These findings suggest that DeltaNp63alpha plays an anti-differentiation
      and anti-apoptotic role in the mucosal epithelium of the head and neck, possibly
      playing a pivotal role in the formation of HNSCC. Currently, DeltaNp63alpha is an
      attractive target for mechanistic study aimed at therapeutic intervention.

PMID- 15564825
TI  - Effectiveness of multilevel (tongue and palate) radiofrequency tissue ablation
      for patients with obstructive sleep apnea syndrome.
AB  - OBJECTIVES: The primary objective is to determine the effectiveness of multilevel
      (tongue base and palate) temperature controlled radiofrequency tissue ablation
      (TCRFTA) for patients with obstructive sleep apnea syndrome (OSAS). The secondary
      objective is to compare multilevel TCRFTA to nasal continuous positive airway
      pressure (CPAP). STUDY DESIGN AND METHODS: The study is a controlled case series
      of one investigator's experience with multilevel TCRFTA for patients with OSAS.
      Twenty-two subjects with mild to severe OSAS, without tonsil hypertrophy,
      completed multilevel TCRFTA (mean 4.8 tongue base and 1.8 palate treatment
      sessions) and had both pre- and posttreatment polysomnography. Primary outcomes
      included change from baseline in apnea/hypopnea index (AHI), daytime somnolence,
      and reaction time testing measured 2 to 3 months after TCRFTA. Secondary outcomes
      included change in other respiratory parameters, OSAS related quality of life,
      and upper airway size. Comparison of 18 patients treated with TCRFTA for mild to
      moderate OSAS (AHI > 5 and < or = 40) is made with 11 matched patients treated
      with nasal CPAP for mild to moderate OSAS. RESULTS: Multilevel TCRFTA
      significantly improved AHI (P = .001), apnea index (P = .02), as well as
      respiratory and total arousal indices (P = .0002 and P = .01). Significant
      improvement with moderate or large treatment effect sizes were noted for OSAS
      related quality of life (P = .01) and daytime somnolence (P = .0001), with a
      trend toward significant improvement in reaction time testing (P = .06), with
      mean posttreatment normalization of all three outcome measures. Fifty-nine
      percent of subjects demonstrated at least a 50% reduction in AHI to less than 20.
      The targeted upper airway, measured in the supine position, demonstrated a trend
      toward significant improvement in mean cross sectional area (P = .05) and volume
      (P = .10). Side effects of TCRFTA were infrequent, mild, and self-limited. No
      significant correlation between pretreatment parameters and outcome improvement
      was noted. Nasal CPAP resulted in significant improvement in AHI (P = .0004) to
      near normal levels, with an associated improvement in OSAS related quality of
      life (P = .02) and a trend toward significant improvement in daytime somnolence
      (P = .06). Reaction time testing demonstrated no significant improvement (P =
      .75). No significant differences were seen for change in AHI, OSAS related
      quality of life, daytime somnolence, or reaction time testing between multilevel
      TCRFTA and CPAP. CONCLUSION: Multilevel (tongue base and palate) TCRFTA is a low
      morbidity, office-based procedure performed with local anesthesia and is an
      effective treatment option for patients with OSAS. On average, abnormalities in
      daytime somnolence, quality of life, and reaction time testing demonstrated
      improvement from baseline and were normalized after treatment. Polysomnographic
      respiratory parameters also demonstrated significant improvement with multilevel
      TCRFTA.

PMID- 15564826
TI  - Intratympanic gentamicin for Meniere's disease: a meta-analysis.
AB  - OBJECTIVES: To systematically review the published experience on intratympanic
      gentamicin treatment for intractable Meniere's disease. STUDY DESIGN: Meta
      analysis using a random effect model. METHODS: A comprehensive literature search
      was performed for articles using intratympanic gentamicin as a sole treatment
      modality with reporting of results according to the American Academy of
      Otolaryngology Head and Neck Surgery (AAO-HNS) guidelines for Meniere's disease.
      Two reviewers independently assessed trial quality and extracted data. RESULTS:
      Fifteen trials with 627 patients met the inclusion criteria. All trials reported
      "before-after" outcome measures, using patients as their own controls. No double
      blind or blinded prospective control trials were identified. Complete (class A)
      vertigo control was achieved in 74.7% (confidence interval [CI]95% 67.8-81.5%) of
      patients, and complete or substantial (class B) control was achieved in 92.7%
      (CI95% 89.5-96.0%). The success rate was not affected by gentamicin treatment
      regimen (fixed vs. titration). Hearing level and word recognition were not
      adversely affected, regardless of gentamicin treatment regimen. Analysis of
      functional level was not performed because of lack of data in the selected
      articles. CONCLUSIONS: Intratympanic gentamicin treatment for intractable
      Meniere's disease appears to be effective in the relief of vertigo.
      Cochleotoxicity and ototoxicity is unlikely to be a major side effect. However,
      the level of evidence reflected from the eligible articles is insufficient,
      especially because of relatively poor study design. Therefore, it is prudent that
      patients eligible for this type of treatment should be selected carefully and
      titrated with low-dose gentamicin. Further investigation with this treatment
      modality with control subjects is warranted.

PMID- 15564827
TI  - Auricular cartilage grafts and nasal surgery.
AB  - OBJECTIVE: To illustrate the safety, effectiveness, and versatility of auricular
      cartilage grafts in nasal surgery. STUDY DESIGN: Retrospective chart review of
      the author's nasal surgery experience for an 8-year period. METHODS: Five hundred
      eight rhinoplasties were performed over an 8-year period. One hundred one of
      these cases used auricular cartilage grafts as donor material. RESULTS: Donor
      cartilage was used in a wide range of grafting techniques: tip grafts, dorsal
      onlays, spreader grafts, septal replacements, alar battens, composite grafts,
      etc. The average follow up was 12 months. The complication rate was low. Five
      patients experienced complications involving the auricular cartilage graft or its
      donor site. No patients experienced graft resorption or infection. Donor site
      morbidity was limited. No auricular infections or hematomas were observed.
      CONCLUSION: Septal cartilage is usually the first choice as donor material in
      nasal surgery; however, when indicated, auricular cartilage grafts can serve as a
      safe, effective, and versatile alternative. This conclusion is supported by their
      successful use in a wide variety of surgical techniques, with long-term follow
      up. The author feels strongly that autografts should be favored over alloplastic
      material. Alloplastic grafts continue to present a risk of infection over the
      entire life of their use. When a rhinoplasty is performed skillfully with a
      cartilage autograft, time becomes an ally of the surgeon rather than an enemy.

PMID- 15564828
TI  - Surgical management of chronic sinusitis in children.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to compare three common surgical
      modalities in children for the treatment of chronic sinusitis that is refractory
      to medical management. STUDY DESIGN: Prospective nonrandomized study in a
      pediatric otolaryngology tertiary service. METHODS: Two hundred two children who
      satisfied criteria for surgery and were referred over a 10-year period were
      studied. Children were divided into three surgical groups. Group 1 had both
      endoscopic sinus surgery and adenoidectomy, group 2 had endoscopic sinus surgery
      alone, and group 3 had adenoidectomy. After a follow-up period of 12 months,
      improvement of symptoms was assessed. RESULTS: One hundred eighty-three children
      had adequate follow-up. Eighty seven percent of children in group 1 had improved
      symptoms, compared with 75% in group 2 and 52% in group 3 (P < .0001).
      Multivariate analysis showed that surgical procedure was a predictor of success.
      Asthma, smoke exposure, and age were independent predictors of success.
      CONCLUSION: Children who fail medical therapy benefit from surgery. Following
      certain criteria, one can chose between adenoidectomy alone or endoscopic sinus
      surgery with adenoidectomy to optimize surgical treatment of these children.

PMID- 15564829
TI  - Prognostic factors in well-differentiated thyroid carcinoma.
AB  - OBJECTIVES: To test the prognostic significance of standard clinicopathologic
      factors in patients with well-differentiated thyroid carcinoma (WDTC). STUDY
      DESIGN: A retrospective chart review of the thyroid cancer database at Mount
      Sinai Hospital (Toronto, Canada 1963-2000) was carried out. METHODS: All patients
      consecutively treated for WDTC with a follow-up period of at least 5 years were
      eligible for inclusion. Relevant patient, tumor, treatment, and outcome data were
      collected. The main outcome measures were recurrence rate, actuarial overall, and
      disease-specific survival at 20 years. RESULTS: Three hundred and thirty-three
      patients (F 275, M 58) with a median age of 39.7 (range 9-82.9) years were
      eligible for inclusion in this study (median follow-up 10.4 years, range 5-34.4
      years, minimum 5 years). The recurrence rate was 15.6% (52 /333). The overall and
      disease-specific survival at 10 years was 97.5% and 98.5%, respectively.
      Likewise, the overall and disease-specific survival at 20 years was 88.4% and
      93.3%, respectively. Clinicopathologic factors significant on multivariate
      regression for the development of disease recurrence included family history of
      WDTC, advanced stage, and total thyroidectomy (all P < .05). Similarly, advanced
      stage on presentation was associated with a worse disease-specific survival on
      multivariate regression (all P < .05). There was a trend for age 60 or greater to
      predict disease-specific survival (P = .09). CONCLUSIONS: WDTC is associated with
      a significant recurrence rate but good disease-specific survival. The most
      important prognostic factors are family history of WDTC, extent of surgical
      treatment (i.e., total thyroidectomy), and advanced initial stage of disease,
      with a trend for age 60 years and older.

PMID- 15564830
TI  - Cochlear implant fixation using polypropylene mesh and titanium screws.
AB  - HYPOTHESIS: Fixation of cochlear implants using prosthetic mesh is an improvement
      of the traditional fixation methods. STUDY DESIGN: A retrospective chart review
      was performed examining all adult and pediatric patients between 1998 and 2003
      who underwent cochlear implantation using polypropylene mesh and titanium screws
      to fix the cochlear implant internal receiver. Patient age at implantation,
      postoperative infections, device failures, device migrations or extrusions,
      cerebrospinal fluid (CSF) leaks, flap complications, epidural hematoma data, and
      follow-up data were evaluated. RESULTS: Two hundred and eighty-five patients were
      identified who received cochlear implantation using the polypropylene mesh
      securing technique. There were five postoperative infections, two device
      failures, zero flap complications, zero device migrations or extrusions, zero
      cerebral spinal fluid leaks, and zero epidural hematomas. The two delayed device
      failures in this series were not related to fixation technique. CONCLUSIONS: We
      conclude that this technique is widely applicable, technically superior, and not
      associated with increased complications.

PMID- 15564831
TI  - Prevalence and epidemiology of hepatitis C virus in patients with squamous cell
      carcinoma of the head and neck.
AB  - OBJECTIVE: Recently, we have noticed that a large number of patients with
      squamous cell carcinoma of the head and neck (SCCHN) are also infected with the
      hepatitis C virus (HCV). A review of the literature has revealed no published
      studies examining this association. The objective of this study was to determine
      the incidence and epidemiology of HCV infection in patients with SCCHN. STUDY
      DESIGN: A retrospective chart review. METHODS: Patients diagnosed with SCCHN were
      analyzed to determine whether they were screened for HCV. Patients were then
      stratified into two groups (HCV positive and HCV negative). The patient's age at
      onset, site and stage of the tumor at presentation were determined, and
      statistical analysis was performed. RESULTS: Ninety-nine (26%) patients were
      screened, and 21 (21.2%) were HCV positive. This incidence was increased when
      compared with previously published data (9.9%) (P < .0038). HCV-positive patients
      presented at an earlier age (51 years) versus the HCV-negative group (60 years)
      (P < .0002). There were no significant differences in the site or stage at
      presentation. CONCLUSIONS: In this study, 21% of patients diagnosed with SCCHN
      were found to be infected with HCV. These patients presented at an earlier age
      but had similar presentation with respect to site and stage. More research is
      needed to determine the significance of HCV infection in this patient population.

PMID- 15564832
TI  - Assessment of gene expression in head and neck carcinoma using laser capture
      microdissection and real-time reverse transcription polymerase chain reaction.
AB  - OBJECTIVES: To quantify gene expression in tumor cells from human head and neck
      squamous cell carcinomas (HNSCC) using laser capture microdissection (LCM). STUDY
      DESIGN: Histopathologically identified HNSCC cells were microdissected from
      frozen sections, RNA was isolated, and vascular endothelial growth factor (VEGF)
      gene expression was measured by real-time reverse transcriptase polymerase chain
      reaction (RT-PCR). MATERIALS AND METHODS: Two human HNSCC tumor samples and
      matched normal mucosal biopsies and five human xenograft tumor specimens were
      harvested, embedded, and frozen in OCT. The frozen tumors were sectioned to 8 to
      10 mum in thickness, and hematoxylin-eosin (H&E) staining was performed before
      LCM. An estimated 2,000 to 3,000 tumor cells were microdissected from frozen
      sections and processed for RNA isolation. mRNA for VEGF was analyzed by real time
      RT-PCR (TaqMan) with commercially available primers and probes. RESULTS: Two
      thousand to 3000 cells were necessary to obtain a suitable quantity of RNA for
      subsequent gene expression study by real-time RT-PCR. The gene expression of
      VEGF, a major tumor angiogenic factor, was tested in microdissected HNSCC and
      compared with uninvolved normal mucosal controls. A greater than seven-fold
      increase of VEGF expression in tumor specimens versus mucosal controls was
      observed. CONCLUSIONS: LCM is a novel sample conserving technique that allows the
      precise selection of tumor cells from a heterogeneous architecture. The
      combination of LCM and real-time RT-PCR appears particularly efficacious for
      studying HNSCC molecular pathogenesis and identifying tissue-specific biomarkers.

PMID- 15564833
TI  - Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for
      laryngopharyngeal reflux disease.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to investigate the potential use of
      pepsin and carbonic anhydrase isoenzyme III (CA-III) as diagnostic markers for
      laryngopharyngeal reflux disease. STUDY DESIGN: Prospective cell biological
      investigation was conducted of laryngeal biopsy specimens taken from 9 patients
      with laryngopharyngeal reflux disease and 12 normal control subjects using
      antibodies specific for human pepsin (produced in the authors' laboratory within
      the Department of Otolaryngology at Wake Forest University Health Sciences,
      Winston-Salem, NC) and CA-III. METHODS: Laryngeal biopsy specimens were frozen in
      liquid nitrogen for Western blot analysis and fixed in formalin for pepsin
      immunohistochemical study. Specimens between two groups (patients with
      laryngopharyngeal reflux disease and control subjects) were compared for the
      presence of pepsin. Further analyses investigated the correlation between pepsin,
      CA-III depletion, and pH testing data. RESULTS: Analysis revealed that the level
      of pepsin was significantly different between the two groups (P < .001).
      Secondary analyses demonstrated that presence of pepsin correlated with CA-III
      depletion in the laryngeal vocal fold and ventricle (P < .001) and with pH
      testing data in individuals with laryngopharyngeal reflux disease. CONCLUSION:
      Pepsin was detected in 8 of 9 patients with laryngopharyngeal reflux disease, but
      not in normal control subjects (0 of 12). The presence of pepsin was associated
      with CA-III depletion in the laryngeal vocal fold and ventricle. Given the
      correlation between laryngopharyngeal reflux disease and CA-III depletion, it is
      highly plausible that CA-III depletion, as a result of pepsin exposure during
      laryngopharyngeal reflux, predisposes laryngeal mucosa to reflux-related
      inflammatory damage.

PMID- 15564834
TI  - Auditory brainstem implantation in patients with neurofibromatosis type 2.
AB  - OBJECTIVES: Multichannel auditory brainstem implants (ABI) are currently
      indicated for patients with neurofibromatosis type II (NF2) and schwannomas
      involving the internal auditory canal (IAC) or cerebellopontine angle (CPA),
      regardless of hearing loss (HL). The implant is usually placed in the lateral
      recess of the fourth ventricle at the time of tumor resection to stimulate the
      cochlear nucleus. This study aims to review the surgical and audiologic outcomes
      in 18 patients implanted by our Skull Base Surgery Team from 1994 through 2003.
      STUDY DESIGN: A retrospective chart review of 18 patients with ABIs. METHODS: We
      evaluated demographic data including age at implantation, number of tumor
      resections before implantation, tumor size, surgical approach, and postoperative
      surgical complications. The ABI auditory results at 1 year were then evaluated
      for number of functioning electrodes and channels, hours per day of use,
      nonauditory side effect profile and hearing results. Audiologic data including
      Monosyllable, Spondee, Trochee test (MTS) Word and Stress scores, Northwestern
      University Children's Perception of Speech (NU-CHIPS), and auditory sensitivity
      are reported. RESULTS: No surgical complications caused by ABI implantation were
      revealed. A probe for lateral recess and cochlear nucleus localization was
      helpful in several patients. A range of auditory performance is reported, and two
      patients had no auditory perceptions. Electrode paddle migration occurred in two
      patients. Patient education and encouragement is very important to obtain maximum
      benefit. CONCLUSIONS: ABIs are safe, do not increase surgical morbidity, and
      allow most patients to experience improved communication as well as access to
      environmental sounds. Nonauditory side effects can be minimized by selecting
      proper stimulation patterns. The ABI continues to be an emerging field for
      hearing rehabilitation in patients who are deafened by NF2.

PMID- 15564835
TI  - Hearing loss in Union Army veterans from 1862 to 1920.
AB  - OBJECTIVES: To examine the prevalence of hearing loss (HL) in Union Army (UA)
      veterans by year, birth cohort, and occupation, and to compare Civil War pension
      and contemporary disability programs by examining monthly dollar awards. STUDY
      DESIGN: A retrospective review of medical records for 17,722 UA veteran pension
      applicants, a subset of some 35,000 soldiers retrieved randomly from the Military
      Archives. METHODS: The diagnosis of HL was based on review of medical records,
      which used gross measurements because of the unavailability of audiometric
      testing. RESULTS: One third (5,891 or 33%) of pensioners sampled received
      compensation for HL. The veterans with HL suffered predominantly from left-sided
      HL (4,091 or 70%), which is consistent with noise-induced HL in a right-handed
      individual firing a rifle. Comparison of civilian occupations reveals minimal
      variation in prevalence of HL. Civil War pensions for unilateral HL averaged
      $134.04 per year, representing nearly one third of the average annual income in
      1890. Bilateral HL received nearly twice that amount. Today, military veterans
      receive $1,248 annually for unilateral loss and $27,288 annually for bilateral
      loss. Social Security disability benefits are granted only for bilateral HL, with
      an average 60-year-old individual receiving $11,400 per year. CONCLUSION: HL was
      a common disability among UA Civil War veterans, with noise exposure a likely
      etiology for the HL. The differing levels of compensation for HL may reflect
      differing perceptions on the incapacitating effects of HL.

PMID- 15564836
TI  - Validating the subcutaneous model of injectable autologous cartilage using a
      fibrin glue scaffold.
AB  - PURPOSE: To create and validate an injectable model for autologous in vivo
      cartilage engineering with ultimate clinical applicability in human subjects.
      HYPOTHESIS: Cartilage can be generated subcutaneously using fibrin glue and
      autologous chondrocyte components. BACKGROUND: To date, cartilage engineering
      studies have been limited by several factors. Immunocompromised animals and
      nonautologous chondrocytes have been successfully used to create cartilage, but
      results using identical designs failed in immunocompetent subjects. Recent
      studies using more biocompatible tissues and matrices have been performed with
      both in vitro and in vivo steps. Although successful, several problems are
      notable. In vitro cartilage displays a poor modulus of elasticity, even after in
      vivo implantation. Variable deformation and volume loss occurs when in vitro
      specimens are matured in vivo. These concerns limit the clinical utility of these
      methods. We therefore set out to create autologous cartilage using a model that
      was clinically feasible, easy to create, and could be performed with very low
      patient harvest morbidity. MATERIALS AND METHODS: Eight New Zealand white rabbits
      underwent a unilateral harvest of ear cartilage. Samples were then digested using
      standard methods. Cell counts and survival assays were performed before
      implantation. One sample of fibrin glue (Tisseel) and chondrocytes was injected
      subcutaneously into each donor rabbit and then left in situ for 3 months. A
      second sample with both basic fibroblast growth factor (b-FGF) and insulin-like
      growth factor (IGF)-1 in the injection suspension was also assessed (for a total
      of 16 samples). After harvest, analysis of overall volume, histology, and
      chondrocyte drop out counts was performed. RESULTS: Cartilage formation occurred
      in 8 of 14 (57%) specimens that were obtained at the time of sacrifice. Of note,
      6 of 7 (85%) non-growth-factor containing samples yielded positive results.
      Comparison with the success rate using concomitant growth factors (2/7) showed a
      negative effect on cartilage yield (P = .015). Chondrocyte survival, based on
      chondrocyte dropout counts, was not effected. Angiogenesis appeared to correlate
      with cartilage formation in the central regions of the implant. Alcian blue
      demonstrated the presence of active matrix deposition, and elastin Verhoff-van
      Geison (EVG) stains were positive, showing an elastic cartilage phenotype. Very
      limited osteoid formation was seen in successful implants. Failed implants
      demonstrated avascular necrosis, giant cell reactions, and inflammatory
      infiltrates. CONCLUSIONS: This study validates the subcutaneous site as a
      recipient bed for the engineering of autologous cartilage in vivo. It also
      represents the first subcutaneous implantation of fibrin glue and chondrocytes in
      an immunocompetent host as well as the first published report of elastic
      cartilage generation in vivo. Although the model needs to be further streamlined
      to increase yields and overall volume, this study clearly demonstrates the
      feasibility of in vivo chondrogenesis (85% success). The addition of FGF and IGF
      1 at the concentrations used negatively influenced cartilage yield. However,
      extrapolation of these results to other combinations or concentrations can not be
      done, and this issue deserves further investigation.

PMID- 15564837
TI  - Therapeutic potential of growth factors for aging voice.
AB  - OBJECTIVES/HYPOTHESIS: It has been reported that in aged vocal folds, dense
      collagen deposition takes place and hyaluronic acid decreases in the lamina
      propria, which are thought to contribute to the vocal problems occurring with age
      (presbyphonia). To restore aged vocal folds to their younger state, it seems
      crucial to address these age-related lamina propria changes. Intervention that
      might increase hyaluronic acid and decrease collagen would appear to be a
      potentially useful approach. The present study examined the effects of growth
      factors on aged fibroblasts in terms of the production of hyaluronic acid and
      collagen type I. STUDY DESIGN: In vitro study using animal model. METHODS:
      Fibroblasts were harvested from young and aged rat vocal folds and cultured with
      or without hepatocyte growth factor and/or basic fibroblast growth factor at
      different concentrations. Subsequently, the production of hyaluronic acid and
      collagen type I was examined in the supernatant culture media using enzyme-linked
      immunosorbent assay. RESULTS: Aged fibroblasts produced less hyaluronic acid than
      younger fibroblasts. When aged and young fibroblasts were cultured with basic
      fibroblast growth factor, hyaluronic acid production increased and collagen type
      I production decreased regardless of the concentration, whereas the effects of
      hepatocyte growth factor appeared to vary with concentration. The basic
      fibroblast growth factor also was associated with stimulation of growth of aged
      fibroblasts. CONCLUSION: The present results suggest that growth factors,
      especially basic fibroblast growth factor, may have therapeutic potential in
      restoration of aged vocal fold.

PMID- 15564838
TI  - Preoperative ultrasound is worthwhile for reoperative parathyroid surgery.
AB  - OBJECTIVES/HYPOTHESIS: High-resolution ultrasound and sestamibi scanning are
      regarded as the first-line methods for preoperative localization of parathyroid
      adenomas. The utility of ultrasound in reoperative cases has been questioned
      because of concern that scarring will obscure normal tissue planes and
      vascularity that are critical to identification of an adenoma using this imaging
      modality. The purposes of the study were to evaluate the ability of high
      resolution ultrasound to accurately localize parathyroid adenomas in the
      reoperative exploration and to identify any factors that influence its accuracy
      STUDY DESIGN: Retrospective chart review at a tertiary care academic medical
      center. METHODS: All patients seen in referral for parathyroid surgery between
      May 1994 and September 2002 underwent high-resolution ultrasound as their initial
      diagnostic test. Patients who subsequently underwent exploration were included in
      the study. Intraoperative and ultrasound findings were compared. RESULTS: One
      hundred forty-two patients were included, 116 without and 26 with prior
      exploration. The sensitivity and positive predictive value of ultrasound were
      86.9% and 89.1%, respectively. These data were not significantly different in
      patients without (88.2% and 90%) and in patients with (80% and 84.2%) prior
      thyroid or parathyroid surgery. The overall accuracy was 79% with a false
      negative rate of 11.3%. Thyroid nodularity was significantly more common (81.8%)
      in patients who had a false-positive or false-negative finding on ultrasound than
      in the total population (61.3%). CONCLUSION: High-resolution ultrasound is an
      accurate method for localizing parathyroid adenomas even in patients who have
      previously undergone parathyroid exploration. However, the presence of thyroid
      nodules can interfere with its accuracy.

PMID- 15564839
TI  - Vestibular evoked myogenic potentials in acute low-tone sensorineural hearing
      loss.
AB  - OBJECTIVE/HYPOTHESIS: It was the authors' premise that the vestibular evoked
      myogenic potential (VEMP) test may be used to differentiate acute low-tone
      hearing loss (ALHL) from Meniere's disease with low-tone HL. STUDY DESIGN:
      Prospective study. METHODS: From January 2000 to December 2002, consecutive 12
      patients with ALHL and another 12 patients with definite Meniere's disease with
      low-tone HL were enrolled in this study. All patients underwent audiometry and
      VEMP test, before and after treatment with isosorbide for 3 consecutive months.
      RESULTS: Before treatment, 12 patients with ALHL revealed normal VEMPs (11, 92%)
      and augmented VEMPs (1). After treatment, 11 (92%) patients had resolved to
      normal hearing within 3 days. One year later, two (17%) patients progressed to
      Meniere's disease. In comparison with Meniere's disease, 6 (50%) of 12 patients
      showed normal VEMPs before treatment, and 7 (58%) patients had their hearing
      improved 3 months after treatment. Comparison of VEMP responses or hearing
      outcome between both groups exhibited significant differences. CONCLUSION: Most
      patients with ALHL reveal normal VEMPs throughout the episode, indicating that
      the saccule is spared. In contrast, 50% of Meniere's disease patients with low
      tone HL demonstrate abnormal VEMPs, showing a significant difference. Therefore,
      the VEMP test can be used to differentiate ALHL from Meniere's disease with low
      tone HL.

PMID- 15564840
TI  - Evaluation of recurrent nerve paralysis due to thoracic aortic aneurysm and
      aneurysm repair.
AB  - OBJECTIVES: We sought to clarify the relationship between the outcome of
      recurrent laryngeal nerve paralysis with the characteristics of the thoracic
      aortic aneurysm and the surgical procedure used in each patient. METHODS: Nine
      patients who developed recurrent nerve paralysis (nonsurgical paralysis) due to a
      thoracic aortic aneurysm alone and 14 patients who underwent artificial vessel
      replacement for thoracic aortic aneurysm and developed recurrent nerve paralysis
      postoperatively (surgical paralysis) were evaluated. RESULTS: In the patients
      with nonsurgical paralysis, the aneurysms were similar in size to those of other
      patients who underwent surgery of the thoracic aorta and were invariably located
      near the aortic arch. Aneurysm shape was not associated with nerve paralysis.
      Surgical paralysis was alleviated in two patients. Surgical paralysis was
      observed in 9% of those who underwent surgery of the thoracic aorta. Vocal cord
      mobility recovered in 4 of the 11 patients with surgical paralysis who underwent
      follow-up. Symptoms were alleviated by rehabilitation in many patients who did
      not recover vocal cord mobility. The positions of the artificial vessel
      anastomoses are thought to be closely related to the outcome of paralysis.
      CONCLUSION: Recurrent nerve paralysis reduced not only the patient's quality of
      life but also survival by leading to disorders including aspiration pneumonia.
      Therefore, early rehabilitation should be performed, and surgical treatment
      should be considered, if necessary, for patients with recurrent nerve paralysis.

PMID- 15564841
TI  - Familial non-medullary thyroid cancer: a matched-case control study.
AB  - OBJECTIVES: Familial non-medullary thyroid cancer (FNMTC) is a newly recognized
      disease entity and can be distinguished from the more common sporadic non
      medullary thyroid cancer. The purpose of this study was to determine some of the
      potential distinguishing features of FNMTC. STUDY DESIGN: Retrospective
      association study and matched-case control study. METHODS: Five hundred forty
      three cases of well-differentiated follicular origin thyroid cancers were
      identified and collected in a database. Among this population, 24 cases of FNMTC
      were identified. A case of FNMTC was defined as a patient with the following two
      criteria: a well-differentiated follicular origin thyroid cancer and at least one
      first-degree relative with a well-differentiated epithelial origin thyroid
      cancer. The unmatched sporadic and FNMTC groups were compared using t test, Phi
      test, Cramer V test, and Pearson and Spearman correlation tests. Twenty-four
      FNMTC cases were matched to 24 sporadic cases based on age, gender, stage of
      disease at presentation, and tumor size. Clinicopathologic features, management,
      and outcome were analyzed statistically using a matched-proportional z test.
      Disease-free survival and disease-specific survival were analyzed using log-rank
      test and the Kaplan-Meier function. A P-value less than .05 was considered
      statistically significant. RESULTS: : There was no significant difference in
      ionizing radiation exposure, disease multifocality, surgical management, or
      recurrence between the sporadic and FNMTC patients. Although FNMTC patients tend
      to have improved disease-free survival and disease-specific survival, the
      difference was not significant at the 5% level. CONCLUSION: Although FNMTC is
      characterized by strong family history, these patients do not tend to have worse
      prognosis.

PMID- 15564842
TI  - Microtia chondrocytes as a donor source for tissue-engineered cartilage.
AB  - OBJECTIVES/HYPOTHESIS: Current surgical techniques for the correction of microtia
      are challenging. Research in the field of tissue engineering is providing insight
      into chondrocyte behavior for a possible future treatment of microtia. The
      authors wished to evaluate the biological potential of chondrocytes isolated from
      microtia cartilage as compared with normal auricular cartilage as a source of
      tissue-engineered cartilage. STUDY DESIGN: A comparative research design to study
      the potential of microtia cartilage chondrocytes with normal auricular
      chondrocytes as a source of tissue-engineered cartilage. METHODS: Cartilage
      specimens from 12 pediatric patients (six normal auricular specimens and six
      auricular specimens with microtia) were obtained. The chondrocytes were isolated
      and cultured in vitro; chondrocyte number was increased by passaging. Each type
      of cell was implanted in nude mice to generate tissue-engineered cartilage. Eight
      weeks after implantation the specimens were dissected and removed. Results were
      compared between the normal auricular and microtia specimens in regard to cell
      number expansion in vitro and generation of tissue-engineered cartilage in vivo.
      RESULTS: An initial mean cell number of 150,000 cells in each group (normal and
      microtia) increased to an average cell number of 120 million cells/mL in the
      normal and 130 million cells in the microtia subgroups, respectively, at the end
      of the second passage. Histologically, both types of chondrocytes generated
      normal elastic cartilage. CONCLUSION: The study demonstrated the potential of
      cells isolated from microtia cartilage to generate tissue-engineered cartilage.
      Microtia cartilage represents an important additional donor source for the
      possible generation of a human tissue-engineered auricle.

PMID- 15564843
TI  - Cochlear implant surgery at 12 months of age or younger.
AB  - OBJECTIVES: Early presentation of congenitally deaf children for cochlear
      implantation is leading to surgery in younger candidates. The safety of cochlear
      implantation in children aged 12 months and younger is reviewed with radiologic
      assessment of mastoid bone anatomy and surgical outcome data. STUDY DESIGN:
      Analysis of case records and temporal bone computed tomography (CT) scans with
      description of surgical technique in infants. METHODS: Chart analysis of children
      aged 12 months or younger at cochlear implantation. Mastoid bone anatomy was
      compared with older children (mean age 2 years) using CT scans. RESULTS: Twenty
      five infants received implants at 7 to 12 months of age because of meningitis (n
      = 4) or early detection of deafness (n = 21). Mastoid marrow content on CT scan
      was significantly greater in this age group (P < .001 Mann-Whitney rank sum
      test), but pneumatization was always adequate for safe identification of surgical
      landmarks. The smaller size of the mastoid bone was not restrictive. An extended
      postauricular approach was used in the first 11 cases and a 2.5 cm hair-line
      incision in the remainder. Ligature tie-down of the device was completed in all
      cases. No complications occurred. All are full-time implant users, except one
      with other neurologic sequelae of preoperative meningitis. CONCLUSIONS: In our
      experience, cochlear implant surgery is safe in children aged 7 to 12 months with
      appropriate anesthetic and postoperative support. The small incision technique is
      particularly suited to this age group. Ligature fixation of the device is
      considered advisable because of the increased risk of displacement from frequent
      falls when learning to walk.

PMID- 15564844
TI  - Bilateral glossopharyngeal nerve paralysis after tonsillectomy: case report and
      anatomic study.
AB  - OBJECTIVE: To present a case report and to propose an anatomic explanation for a
      rare complication of tonsillectomy, severe dysphagia caused by bilateral
      paralysis of the glossopharyngeal nerve. STUDY DESIGN: Retrospective case review
      and prospective cadaveric dissection. METHODS: The medical record and radiologic
      data were reviewed from a patient who had severe dysphagia after tonsillectomy.
      In addition, 10 formalin-preserved cadaver head and neck specimens were dissected
      to identify the anatomic course of 20 glossopharyngeal nerves. The distance
      between the nerve and tonsillar fossa was measured at two sites. RESULTS: The
      patient was diagnosed with bilateral paralysis of the glossopharyngeal nerve and
      required use of gastrotomy tube for years postoperatively. The mean distance from
      the posterosuperior tonsillar fossa and the main trunk of the glossopharyngeal
      nerve was 10.7 mm, and the mean distance from the posteroinferior tonsillar fossa
      and the closest lingual branch of the glossopharyngeal nerve was 6.5 mm.
      CONCLUSIONS: Direct nerve injury seems the most plausible explanation for this
      rare complication of tonsillectomy. The proximity of the glossopharyngeal nerve
      to the tonsillar fossa emphasizes the importance of maintaining the correct
      surgical plane during surgery.

PMID- 15564845
TI  - Treatment of olfactory dysfunction, II: studies with minocycline.
AB  - OBJECTIVES/HYPOTHESIS: The treatment of anosmia has changed minimally since the
      early 1970s, despite dramatic advances in the understanding of the molecular
      biology of olfaction. Recent studies from the authors' laboratory have suggested
      that most common causes of clinical olfactory dysfunction, including
      rhinosinusitis, appear to be associated with increased apoptotic death of
      olfactory sensory neurons. This appears to result in a decline in the number of
      functioning mature olfactory sensory neurons, despite the capacity of the
      olfactory epithelium for regeneration. The current study evaluated the ability of
      the antibiotic minocycline to inhibit olfactory sensory neuron apoptosis. This
      drug is known to inhibit apoptosis separate from its anti-infective properties.
      Olfactory sensory neuron apoptosis was triggered by surgical deafferentation
      ("bulbectomy"), the standard experimental model. Earlier studies have indicated
      that bulbectomy and sinusitis invoke similar proteolytic enzyme cascades in
      olfactory sensory neurons. STUDY DESIGN: Histological analysis of animal
      olfactory tissue. METHODS: Mice underwent unilateral olfactory bulbectomy to
      induce apoptotic olfactory sensory neuron death, with and without 45 mg/kg
      intraperitoneal minocycline given 12 hours before surgery and every 12 hours
      until death. Mice were killed at 2 and 4 days after bulbectomy and assessed for
      activation of capsase-3 and olfactory sensory neuron survival by
      immunohistochemical analysis. RESULTS: Minocycline resulted in partial
      suppression of cell death at 2 days after surgery when compared with untreated
      animals. CONCLUSION: Minocycline inhibits olfactory sensory neuron death in the
      face of a potent pro-apoptotic stimulus. This drug is well tolerated and is
      currently undergoing human trials for the management of a variety of neurological
      disorders associated with apoptosis. The current results suggest that minocycline
      may be efficacious in the management of peripheral olfactory loss as well.

PMID- 15564846
TI  - The woman behind Frey's syndrome: the tragic life of Lucja Frey.
AB  - OBJECTIVE: The auriculotemporal syndrome is known worldwide as Frey's syndrome.
      However, the Jewish physician Lucja Frey, after whom it was named, has fallen
      into obscurity. The little information about her is fragmentary, contradictory,
      and often incorrect. STUDY DESIGN: To reconstruct the life of Lucja Frey, who was
      murdered by the Nazis in her native town of Lwow, it was imperative to look for
      original documents as irrevocable proof of her life. METHODS: During this
      research, more than 100 archives and institutions in 8 countries have been
      contacted. RESULTS: With the archive materials, it was possible for the first
      time to create a complete picture of the life of this fascinating physician.
      Furthermore, her day of death, unknown until now, could be determined with great
      plausibility. The lasting impression is not only of a tragic death under the
      Nazis but also of a tragic life as a whole. CONCLUSION: Lucja Frey would have
      been forgotten if not for the eponym Frey's syndrome. In this way, she is
      remembered not only as an unusual woman, physician, and scientist but also as one
      of millions of Jews murdered by the Nazis. This may be the only key remaining to
      prevent the repetition of one of the most haunting and devastating times in
      history.

PMID- 15564847
TI  - Cervical sympathetic chain schwannoma.
AB  - OBJECTIVES: Schwannomas are benign, slow-growing tumors that arise from nerves.
      Those originating from the sympathetic cervical chain are rare. We describe our
      experience with the clinical presentation, surgical management, and outcomes of
      patients with this pathology. STUDY DESIGN: Retrospective chart review of a case
      series in a tertiary referral center. METHODS: Four cases of cervical sympathetic
      chain schwannomas were reviewed. Patients presented with either an asymptomatic
      neck mass discovered on routine physical examination (1 patient), an enlarging
      neck mass (2), or an acute onset of a Horner's syndrome (1). All patients
      underwent preoperative imaging (magnetic resonance imaging, computed tomography,
      or both). RESULTS: The location and soft-tissue characteristics of the mass,
      along with displacement of the carotid sheath vessels, were typical of a cervical
      sympathetic chain schwannoma. All patients underwent surgical excision of the
      mass. Postoperative Horner's syndrome was encountered in all patients. First bite
      syndrome was encountered in two patients. CONCLUSIONS: Cervical sympathetic chain
      schwannomas are rare tumors. Preoperative imaging characteristics facilitate the
      diagnosis. First bite syndrome can occur and may be debilitating postoperatively.
      Long-term prognosis is excellent.

PMID- 15564848
TI  - Bronchogenic cyst presenting as a symptomatic neck mass in an adult: case report
      and review of the literature.
AB  - We report the unusual clinical manifestation and subsequent management of a
      symptomatic congenital bronchogenic cyst that connected to the trachea and
      presented in the neck of an adult. The embryology, clinical presentation,
      diagnostic evaluation, and management options of this rare aberration are
      discussed.

PMID- 15564849
TI  - Cochlear implantation in patients with substantial residual hearing.
AB  - OBJECTIVES: Cochlear implantation is an effective means for providing auditory
      rehabilitation in adult patients with severe to profound sensorineural hearing
      loss. It has been hypothesized that patients with substantial, preoperative
      residual hearing would be excellent cochlear implant candidates because of
      surviving neural populations and a lack of auditory deprivation. The purpose of
      this study is to describe the outcomes of patients with substantial residual
      hearing who have undergone cochlear implantation. STUDY DESIGN: Retrospective
      chart review of patients with substantial preoperative residual hearing who
      underwent cochlear implantation. METHODS: Chart reviews were completed for
      patients with substantial residual hearing who underwent cochlear implantation
      (City University of New York Sentence Test [CUNY] > 60%, Hearing in Noise Test
      sentences presented in quiet [HINTQ] > 50%, or Consonant-Nucleus-Consonant [CNC]
      > 20% in the ear to be implanted). Preoperative and postoperative measures of
      audiologic performance as well as complications were assessed. RESULTS: All 12
      patients who met inclusion criteria ultimately surpassed their preoperative aided
      performance level after implantation and gained significant benefit from their
      cochlear implant. At 6 months postimplantation, mean CUNY, HINTQ, and CNC scores
      were 93%, 78%, and 48% in the implant ear alone, respectively. However, progress
      was slower than expected for many patients, and at least one patient took 1 year
      to surpass his preoperative performance level. There were no complications from
      surgery in this selected group of patients. CONCLUSIONS: Patients with some
      degree of residual hearing do benefit from cochlear implantation. However, there
      may be an initial decline in performance as compared with preoperative levels.
      This decline is overcome in time in this patient population. These patients need
      to be counseled accordingly.

PMID- 15564850
TI  - A comparative study of three methods of nasal irrigation.
AB  - OBJECTIVE: To assess the effectiveness of three methods of nasal irrigation on
      distributing saline to the nasal cavity and paranasal sinuses. DESIGN: : A
      prospective, cross-over study. MATERIALS AND METHODS: Twelve subjects (9 patients
      with chronic sinusitis after functional endoscopic sinus surgery and 3 healthy
      controls) underwent nasal irrigation with normal saline containing Technetium 99m
      sulfur colloid. The distribution of radioactivity was assessed on each subject
      after three different irrigation techniques: metered nasal spray, nebulization
      with RinoFlow, and nasal douching while kneeling with the head on the floor.
      RESULTS: The nasal cavity was well irrigated by all three techniques. Compared
      with the other two methods, douching was significantly more effective in
      penetrating the maxillary sinus (P = .036) and frontal recess (P = .003). The
      sphenoid and frontal sinuses were poorly irrigated by all three techniques.
      CONCLUSION: Nasal douches are more effective in distributing irrigation solution
      to the maxillary sinus and frontal recess. This should be the method of choice
      for irrigating these areas.

PMID- 15564851
TI  - Elective neck dissection and survival in patients with squamous cell carcinoma of
      the oral cavity and oropharynx.
AB  - OBJECTIVE/HYPOTHESIS: The utility of elective neck dissection in the management
      of patients with oral cavity and oropharyngeal cancer who present without neck
      metastases remains controversial. The study addressed the question of whether
      elective neck dissection improves regional control and survival in patients with
      squamous cell carcinoma of the oral cavity and oropharynx presenting with T1/T2
      node-negative disease. STUDY DESIGN: A nonrandomized, uncontrolled retrospective
      chart review. METHODS: A nonrandomized, uncontrolled retrospective chart review
      was performed. Resection of the primary tumor was performed in all patients. The
      neck was observed in one group, and elective neck dissection was performed for
      patients in another group. RESULTS: The study data indicated that elective neck
      dissection significantly improves regional control and regional recurrence-free
      survival. Elective neck dissection when compared with observation of the neck did
      not improve overall survival. CONCLUSION: Elective neck dissection reduces
      regional recurrence and may extend disease-free survival.

PMID- 15564852
TI  - Detection of herpesvirus DNAs in perilymph obtained from patients with
      sensorineural hearing loss by real-time polymerase chain reaction.
AB  - OBJECTIVES/HYPOTHESIS: Perilymph and peripheral blood mononuclear cells (PBMCs)
      from patients with bilateral severe sensorineural hearing loss (SNHL) were
      evaluated for the presence of DNA from cytomegalovirus (CMV), herpes simplex
      virus (HSV), and human herpesvirus (HHV)6. STUDY DESIGN: A prospective clinical
      study. METHODS: The subjects were 14 patients who underwent cochlear implantation
      and 1 patient who underwent gentamicin injection in the inner ear. We attempted
      to detect viral DNA from perilymph and PBMCs by real-time polymerase chain
      reaction (rtPCR). RESULTS: CMV DNA was detected in two perilymph specimens
      obtained from patients who were diagnosed as congenitally symptomatic CMV
      infection, although no CMV DNA was detected in PBMCs. Neither HSV DNA nor HHV6
      DNA was detected in any other perilymph specimens. CMV DNA was detected in three
      PBMC samples, HSV DNA was detected in two samples, and HHV6 DNA was detected in
      six samples. CONCLUSION: CMV may persistently infect the inner ear of patients
      with congenital CMV infection, and rtPCR analysis may prove to be a valuable tool
      for investigating the etiology of SNHL.

PMID- 15564853
TI  - Cochlear degeneration in leigh disease: histopathologic features.
AB  - OBJECTIVE: To describe pathologic findings from temporal bones acquired from an
      infant with Leigh disease. STUDY DESIGN: Retrospective case review. MATERIALS AND
      METHODS: Temporal bones were taken at autopsy from an 8-month-old infant with
      Leigh disease. The right temporal bone was studied by microdissection. The middle
      ear was examined and the inner ear sensory organs dissected for study by light
      microscopy. The left temporal bone was embedded in celloidin, and sections were
      cut for microscopic examination. RESULTS: Middle ear structures were normal
      bilaterally. There was, however, evidence of otitis media in both middle ears,
      which was more severe on the left side. Inner and outer hair cell loss, patchy
      degeneration of organ of Corti, and loss of nerve fibers in the osseous spiral
      lamina were found in the basal and middle turns of both cochleas. Basophilic
      deposits in the stria vascularis were observed in the apical portion of the left
      cochlea. CONCLUSIONS: Inner ear sensorineural degeneration may occur in Leigh
      disease. Possible cochlear dysfunction caused by the degenerative changes needs
      to be considered in the hearing assessment of patients with Leigh disease.

PMID- 15564854
TI  - Expression of matrix metalloproteinases in supraglottic carcinoma and its
      clinical implication for estimating lymph node metastases.
AB  - OBJECTIVE: Twenty to 30% of clinically node-negative patients with squamous cell
      carcinoma (SCC) of supraglottic larynx were pathologically confirmed with occult
      lymph node metastasis after operation. Therefore, preoperative judgment on the
      neck node metastasis should be very important for making an appropriate surgical
      plan. The purpose of this study is to explore the role of matrix
      metalloprotineases (MMPs) in the metastatic potential of supraglottic carcinoma
      in this regard. STUDY DESIGN: Examination of MMPs expression in supraglottic
      carcinoma and establishment of the mathematic model for diagnosis of occult lymph
      node metastases in a prospective manner. METHODS: Thirty-two patients with
      supraglottic SCC underwent supraglottic horizontal partial laryngectomy and neck
      dissection, and the samples of primary cancer and the corresponding adjacent non
      neoplastic tissues were evaluated for both mRNA and protein expression of MMP-1,
      MMP-2, MMP-7, MMP-8, MMP-9, and MMP-10 using reverse transcriptase polymerase
      chain reaction (RT-PCR) and immunohistochemistry. In addition, cervical lymph
      nodes were examined by routine histopathology to determine whether there was any
      evidences of node metastasis. RT-PCR and immunohistochemical data were analyzed
      by multivariate logistic regression, and then two mathematical models were
      established according to the multivariate logistic regression analysis. RESULTS:
      Among the six kinds of MMPs, both mRNA and protein expression of MMP-2, MMP-7,
      and MMP-9 were found up-regulated in more than 63% of the tumor tissues as
      compared with the adjacent non-neoplastic tissues, and this was significantly
      correlated with lymph node metastasis (all P < .05). Twenty patients, including
      seven cases with N0, were pathologically confirmed as having cervical lymph node
      metastasis. Using RT-PCR and immunohistochemical data of MMP-2, MMP-7, and MMP-9,
      two mathematic models were tested, and their diagnostic efficiencies for lymph
      node metastasis were 84% and 88%, respectively. CONCLUSION: Expressions of MMP-2,
      MMP-7, and MMP-9 are up-regulated in supraglottic carcinoma tissues, suggesting
      that MMPs may be useful in the detection of occult lymph node metastasis but that
      more research is needed.

PMID- 15564855
TI  - Immunohistochemical localization of histamine receptors in rat cochlea.
AB  - OBJECTIVE: Histamine may have physiologic functions in the inner ear. The
      locations of histamine receptors, however, have not yet been identified in the
      mammalian cochlea. The aim of this study was to investigate the localization of
      histamine receptor subtypes (H1, H2, and H3 receptors) in rat cochlea. METHODS:
      Immunohistochemistry was performed with antibodies specific for each of the
      histamine receptors (H1, H2, and H3). To identify the type I and II spiral
      ganglion cells in the cochlea, some cryostat sections were double stained with
      antibodies to both a histamine receptor and neurofilament 200 kD, which
      predominantly stains type II spiral ganglion cells in the cochlea. RESULTS: All
      H1, H2, and H3 receptor immunoreactive staining was limited to the spiral
      ganglion cells of the cochlea. Spiral ganglion cells with positive
      immunoreactivity to the neurofilament 200 kD antibody were stained only slightly
      by histamine H1, H2, and H3 receptor antibodies, indicating that histamine
      receptor immunoreactivity is specific to type I ganglion cells. CONCLUSIONS:
      These findings indicate that histamine receptors are present in the cochlea and
      support the hypothesis that histamine plays a physiologic role in the cochlea.

PMID- 15564856
TI  - Electrosurgery after cochlear implantation: eighth nerve electrophysiology.
AB  - HYPOTHESIS: Monopolar electrosurgery below the neck in cochlear implant
      recipients can be performed without damage to the internal cochlear stimulator,
      electrode array, and the cochlear nerve. STUDY DESIGN: Prospective pre- and
      postintervention electrically evoked compound action potential (ECAP) study of
      cochlear nerve function and behavioral sound perception assessment. METHODS:
      Neural response telemetry (NRT) was used to measure ECAPs before and after the
      use of monopolar electrosurgery during coronary artery bypass surgery to assess
      prosthetic device function and electrophysiologic function of the cochlear nerve.
      In addition, electrode voltage impedances and behavioral sound perception was
      measured at the same time intervals. RESULTS: ECAPs, behavioral sound perception,
      and electrode voltage impedances were within the normal range, within compliance,
      and similar preoperatively and on postoperative day 6. CONCLUSION: The studies
      reported herein were a series of measurements designed to test neural integrity
      and prosthetic device function before and after the use of monopolar
      electrosurgery. With appropriate precautions, use of monopolar electrosurgery
      below the neck in cochlear implant recipients can be performed safely.

PMID- 15564859
TI  - A comparison of laterally condensed gutta-percha, thermoplasticized gutta-percha,
      and mineral trioxide aggregate as root canal filling materials.

PMID- 15564860
TI  - Nonsurgical retreatment.
AB  - With all the potential for endodontic success, the fact remains clinicians are
      confronted with posttreatment endodontic disease. When the elected treatment plan
      is endodontic nonsurgical retreatment, then the goal is to access the pulp
      chamber and remove materials from the root canal space and if present, address
      deficiencies or repair defects that are pathologic or iatrogenic in origin. This
      article provides a literature review with clinical recommendations for one
      important group of retreatment issues: the removal of posts and broken
      instruments.

PMID- 15564861
TI  - Endodontic treatment outcomes in a large patient population in the USA: an
      epidemiological study.
AB  - Outcome assessment of endodontic treatment is critical for appropriate case
      selection and treatment planning. However, reports on outcomes of nonsurgical
      endodontic treatment vary considerably. Epidemiological studies done in a large
      patient population and over a long follow-up period can provide the clinician
      with useful tools for clinical decision-making and assessment of tooth prognosis.
      In this study, outcomes of initial endodontic treatment done in 1,462,936 teeth
      of 1,126,288 patients from 50 states across the USA was assessed over a period of
      8 yr. Treatment was done by private general practitioners and endodontists
      participating in the Delta Dental Insurance plan that insures approximately 14
      million individuals in the USA. Overall, 97% of teeth were retained in the oral
      cavity 8 yr after initial nonsurgical endodontic treatment. The combined
      incidence of untoward events such as retreatments, apical surgeries, and
      extractions was 3% and occurred mostly within 3 yr from completion of treatment.
      Analysis of the extracted teeth revealed that 85% had no full coronal coverage. A
      significant difference was found between covered and noncovered teeth for all
      tooth groups tested (p < 0.001). In conclusion, it appears that initial
      nonsurgical endodontic treatment is a predictable procedure with high incidence
      of tooth retention after 8 yr.

PMID- 15564862
TI  - Simultaneous detection of Dialister pneumosintes and Filifactor alocis in
      endodontic infections by 16S rDNA-directed multiplex PCR.
AB  - Dialister pneumosintes and Filifactor alocis have been recently considered as
      candidate endodontic pathogens. In this study, we devised a 16S rDNA-directed
      multiplex PCR protocol for simultaneous detection of these two bacterial species
      in endodontic infections. Samples were taken from infected root canals associated
      with asymptomatic periradicular lesions as well as from cases of acute
      periradicular abscesses. DNA extracted from the samples was used as template for
      simultaneous detection of D. pneumosintes and F. alocis through a multiplex PCR
      assay. Two fragments of the expected sizes, one specific for D. pneumosintes and
      the other for F. alocis, were simultaneously amplified from a mixture of
      reference genomic DNA containing DNA from both species. Clinical samples that
      were positive for the target species showed a single band of the predicted size
      for each species. D. pneumosintes was detected by multiplex PCR in 11 samples (7
      asymptomatic and 4 abscesses) and F. alocis was identified in 9 cases (6
      asymptomatic and 3 abscesses). Six samples (3 asymptomatic and 3 abscesses)
      shared the two species. Data from the present study confirmed that D.
      pneumosintes and F. alocis are common members of the microbiota present in
      primary endodontic infections and thereby may participate in the pathogenesis of
      periradicular lesions. The proposed multiplex PCR assay is a simple, rapid, and
      accurate method for the simultaneous detection of these two candidate endodontic
      pathogens.

PMID- 15564863
TI  - Importance of mast cells in human periapical inflammatory lesions.
AB  - The role of mast cells (MCs) in periapical inflammatory lesions is not well
      understood. The objective of this work was to quantify MC numbers in human
      periapical lesions with the aim to clarify their role in the pathogenesis of
      these lesions. We analyzed the slides of 64 human periapical inflammatory lesions
      stained with pH 8.0 toluidine blue technique, quantified the number of MCs, and
      evaluated any correlation with age, gender, size, and location. The results of
      this study suggest that MCs were more numerous in females (p < 0.01); MC numbers
      were higher in biopsies from granulomas with proliferating epithelium and lower
      in biopsies from chronic apical abscesses; MC counts did not correlate with
      patients' age or size. MCs were observed more commonly in areas containing
      inflammatory infiltrate and degranulation was a frequent finding in these zones.
      Our results suggest that MCs play an active role in the pathogenesis of the
      periapical inflammatory lesions. The potential role of MCs related with the
      initiation, development, and persistence of the periapical inflammatory process
      are discussed.

PMID- 15564864
TI  - Optimal positioning for a dental operating microscope during nonsurgical
      endodontics.
AB  - The most comfortable positioning for a dental operating microscope (DOM) during
      nonsurgical endodontics for operators was investigated. Operators were
      categorized into 3 groups according to height. We recorded the time taken to
      obtain magnified images, and the angles of binoculars, microscope body, and the
      mirror to floor surfaces. For the group of shorter operators, observations were
      also made with an angled optics or a short objective lens (200 mm). It took
      longer to observe the mandibular molars than maxillary in every group. Although
      the differences in angles among each group were not remarkable for maxillary
      observation, we confirmed significant differences for the mandibular. Shorter
      operators had to adopt a strained position for mandibular observation in a
      standard setup but were more comfortable using angled optics or a short objective
      lens. By understanding the proper position, operators could learn to perform
      microendodontics more efficiently.

PMID- 15564865
TI  - The benefit of the operating microscope for access cavity preparation by
      undergraduate students.
AB  - Although studies show the operating microscope (OM) provides benefits for
      endodontists, the benefit to undergraduates has not been evaluated as completely
      as for specialists. The purpose of this study was to determine whether using the
      OM would improve students' performance in endodontic access cavity preparation
      and canal identification. Thirty-six dental students prepared access cavities and
      located canals in extracted maxillary molars, before and after training, which
      varied according to group. The standard group received a lecture and practice in
      preparation of access cavities. The microscope group received identical
      instruction using the OM. The control group received lectures only. All groups
      received equal content and instruction time (2 hr 20 min). Faculty graded
      preparations according to a multidimensional 5-point rating scale. Using the OM,
      the microscope group improved significantly in access cavity preparation (p
      <0.05) and significantly outperformed both standard and control groups in
      accuracy of identifying canals (p <0.05).

PMID- 15564866
TI  - Effects of multiple dentinal lesions on the rat pulp.
AB  - The purpose of this study was to compare the effects of single and multiple
      dentinal lesions on the dental pulps of rats. 3H-proline was used to measure
      pulpal reactionary dentin deposition, and 3H-thymidine was used to measure pulpal
      cell proliferation by radioautography. Data were compared by factorial analysis
      of variance and a post-hoc Tukey test. A significant increase in radiolabeled
      collagenous proteins within reactionary dentin and pulpal cell labeling indices
      were evident coincident to single dentinal injuries, compared with controls (p <
      0.001). After double injuries, the radiolabeled collagenous proteins within
      reactionary dentin and the pulpal labeling indices remained significantly greater
      than in controls (p < 0.01); however, each was significantly less than after
      single injuries (p < 0.05). These data suggest that pulpal cell proliferation and
      collagenous protein deposition into reactionary dentin are decreased subsequent
      to a previous dentinal injury. Thus, the healing potential of the dental pulp
      could be decreased by recent tooth cavity preparation.

PMID- 15564867
TI  - Chairside sensor for rapid monitoring of Enterococcus faecalis activity.
AB  - In this study, optical spectroscopy was used to monitor a chromogenic, enzyme
      substrate reaction for the rapid identification of Enterococcus faecalis. The
      detection system, comprising a miniature spectrophotometer and an accompanying
      data acquisition system, was placed in an incubator. During testing, a 3-ml test
      sample was placed in a cuvette within the spectrophotometer. This permitted
      online, real-time, and remote analysis of spectral signature needed to monitor
      the bacteria. It was observed that the absorption peak intensity increased
      conspicuously 3.5 h after inoculation and through the entire period of testing. A
      linear-regression analysis demonstrated a significant correlation between the
      increase in absorption peak intensity at 610 nm (r = 0.9389) and 653 nm (r =
      0.9387) with the formation of colony-forming units. Optical spectroscopy-based
      sensing systems can pave the way for rapid, nonlaboratory-based approaches to
      monitor microbial status quantitatively and qualitatively from clinical samples.

PMID- 15564868
TI  - Comparative study of white and gray mineral trioxide aggregate (MTA) simulating a
      one- or two-step apical barrier technique.
AB  - This study investigated the use of Mineral Trioxide Aggregate (MTA) as an apical
      barrier by comparing the sealing ability and set hardness of white and gray MTA.
      Forty-four root segments were prepared to simulate an open apex. Apical barriers
      of white and gray MTA were placed to a thickness of 2 mm or 5 mm. The samples
      were obturated immediately (one-step) or after the MTA set for 24 h (two-steps).
      After placement in methylene blue dye for 48 h, the samples were sectioned for
      leakage analysis and microhardness testing of the barrier. Gray MTA demonstrated
      significantly less leakage than white MTA (p < 0.001), and the two-step technique
      showed significantly less leakage than one-step (p < 0.006). The 5-mm thick
      barrier was significantly harder than the 2 mm barrier, regardless of the type of
      MTA or number of steps (p < 0.01). Results suggested that a 5 mm apical barrier
      of gray MTA, using two-steps, provided the best apical barrier.

PMID- 15564869
TI  - Effect of sodium hypochlorite on dentin microhardness.
AB  - This study was designed to evaluate the effect on root dentin microhardness of
      2.5% and 6% sodium hypochlorite solutions for various irrigation periods. Forty
      two bovine roots were divided into seven groups. The control group was irrigated
      with saline. The experimental samples were continuously irrigated with 2.5% or 6%
      NaOCl for 5, 10, or 20 min. Microhardness was measured at depths of 500 mum, 1000
      mum, and 1500 mum from the lumen. A decrease in microhardness was found at 500
      mum between the control and samples irrigated with 6% NaOCl and 2.5% NaOCl (p =
      0.352, p = 0.084 respectively) at all irrigation periods. There also was a
      significant difference in groups irrigated for 10 or 20 min (p = 0.001, p < 0.001
      respectively). At all distances, the decrease in microhardness was more marked
      after irrigation with 6% NaOCl than 2.5% NaOCl.

PMID- 15564870
TI  - MTA obturation of pulpless teeth with open apices: bacterial leakage as detected
      by polymerase chain reaction assay.
AB  - Polymerase chain reaction (PCR) followed by reverse dot blot was used to detect
      Enterococcus faecalis leakage through mineral trioxide aggregate (MTA) apical
      obturations of pulpless teeth with open apices. Prepared root canals of 34
      extracted teeth were given a standard apical foramen opening and received
      orthograde apical obturation with MTA; three groups had 1-, 2-, or 3-mm
      thickness. Sterilized specimens were inoculated with E. faecalis and incubated in
      sterile medium. DNA extracted from the specimens was amplified by polymerase
      chain reaction, which yielded a specific segment of E. faecalis 16S rDNA. On day
      10 of incubation, no specimens were contaminated. On day 50, almost 17% of
      specimens were contaminated, with no statistically significant difference between
      groups (Chi-square = 0.48; df = 2; p = 0.787). Therefore, MTA provides an
      adequate seal even in cases of orthograde apical obturation of pulpless teeth
      with open apices.

PMID- 15564871
TI  - Peroxide penetration into the pulp from whitening strips.
AB  - It was observed that externally applied bleaching gels may penetrate into the
      pulp chamber. This study was conducted to evaluate the peroxide diffusion from
      two whitening strips into the pulp chamber. Twenty-four, human, extracted,
      maxillary central teeth were separated into three groups (n = 8). All teeth were
      sectioned 3-mm apical to CEJ, the intracoronal pulp tissue was removed, and the
      pulp chamber was filled with acetate buffer. Vestibuler crown surfaces of teeth
      in the experimental groups were subjected to whitening strips; the teeth in the
      control group were exposed only to distilled water. The acetate buffer solution
      in each tooth was transferred to the tube. Leuco-crystal violet and enzyme
      horseradish peroxidase also were added to the tube. The pulpal peroxide was
      determined spectrophotometrically. The results indicated that the whitening strip
      containing 14% hydrogen peroxide presented a higher pulpal peroxide penetration
      than 6.5 % hydrogen peroxide (p < 0.001).

PMID- 15564872
TI  - The effect of MTAD on the coronal leakage of obturated root canals.
AB  - The purpose of this study was to evaluate the effect of smear-layer removal using
      MTAD on coronal leakage of obturated root canals using a dye-leakage test. Fifty,
      extracted, single-rooted, human teeth were cleaned and shaped and divided into 5
      equal groups of 10 each. The smear layer in groups 1 to 3 was left intact. The
      smear layer in groups 4 and 5 was removed using 17% EDTA or MTAD, respectively.
      After obturation of root canals, the access opening to each canal was filled with
      India ink for 48 h. The depth of coronal-dye penetration was measured using the
      Sigmascan software. ANOVA showed statistically significant differences among the
      groups (p < 0.05). Samples treated with MTAD yielded significantly less leakage
      than samples treated with sodium hypochlorite. The amount of dye penetration was
      not statistically different between teeth treated with MTAD or EDTA (p = 0.062).

PMID- 15564873
TI  - Real-time imaging and quantification of bioluminescent bacteria in root canals in
      vitro.
AB  - The detection of microorganisms in root canals is generally limited to
      qualitative or semiquantitative methods. We describe a new and nondestructive in
      vitro method to quantify root-canal bacteria over sequential treatment procedures
      using real-time imaging in conjunction with the bioluminescent reporter strain
      Pseudomonas fluorescens 5RL. Induced bacterial photon emission can be monitored
      by sensitive optical photonic imaging and luminometry, providing images as well
      as spatial and quantitative measurements. Bioluminescence imaging and luminometry
      determined that the lower limit of detection of bacteria in root canals occurred
      between 2 x 10(2) and 2 x 10(3) cells, with high correlation between cell counts
      and detection devices (r > or = 0.981). A preliminary study assessed the efficacy
      of sequential irrigation procedures to remove 5 x 10(6) bacteria from root canals
      (n = 5; apical size 60) using a 28-gauge, endodontic needle positioned 1 mm from
      working length; 9.2% +/- 3.1% and 8% +/- 3.6% of bacteria remained after 3 and 6
      ml irrigation, respectively (p = 0.03), corresponding to approximately 4 x 10(5)
      bacteria remaining after 6 ml. This method can be used to study the efficacy of
      sequential endodontic treatment procedures in removing bacteria from root canals.

PMID- 15564874
TI  - C-shaped canal system in mandibular second molars: Part I--Anatomical features.
AB  - The purpose of this study was to investigate the anatomical features of C-shaped
      root canal system in mandibular second molars using micro-computed tomography
      (microCT). Fifty-eight extracted mandibular second molars with fused roots were
      collected from a native Chinese population. The teeth were scanned into layers of
      0.5-mm thickness by microCT and measurements were made at eleven levels. The
      ratio of the depth of the deepest part of the groove to the buccal-lingual
      thickness of the cross-section of the root was calculated for each tooth. The
      canal shapes of the scanned cross-sections were assessed and classified according
      to a modified Melton's method. Results were subject to the Kruskal-Wallis test.
      Of the 58 molars, 54 had a C-shaped canal system with a mean groove-to-thickness
      ratio of 47.96%; the four teeth without a C-shaped canal had a mean ratio of
      14.82%. Most orifices (98.1%) were found within 3 mm below the cementoenamel
      junction. Of teeth with a C-shape canal system, a majority demonstrated an
      orifice with an uninterrupted "C" configuration. Seventeen canals divided in the
      apical portion, most of which did so within 2 mm from the apex. The cross
      sectional shape varied drastically along the length of the canal. Teeth with a
      high groove-to-thickness ratio had at least one section with C1, C2, or C3
      configuration. The canal shape in middle and apical thirds of C-shaped canal
      systems could not be predicted on the basis of the shape at the orifice level.
      Section 2 of this paper addressed the correlation between the radiographic
      appearance and these microCT images.

PMID- 15564875
TI  - C-shaped canal system in mandibular second molars: Part II--Radiographic
      features.
AB  - The purpose of this study was to investigate the relation between the
      radiographic features of C-shaped mandibular second molars and the cross
      sectional shapes of their root canal system. Fifty-eight extracted mandibular
      second molars with fused roots were collected from a native Chinese population.
      The teeth were scanned at 0.5-mm interval thickness by micro-computed tomography
      (microCT) and observed at 11 levels. The 54 teeth that possessed a C-shaped canal
      system were further examined. Their radiographic appearances were classified into
      three types according to discernible radiographic features. The results were
      subject to the Kruskal-Wallis statistical test. In these 54 molars, 16 teeth
      (29.63%) showed a type I radiographic image, 22 (40.74%) type II, and 16 (29.63%)
      type III. In the type I category, the C1 and C4 canal configurations were mostly
      found in the apical area. Categories C2 and C3 were the main configurations in
      the middle and apical areas in type II and III. The type III had more C2 canals
      in middle area than type II. These results suggested that it was possible to
      predict the presence and the configuration of C-shaped canal system by the
      radiographic appearance.

PMID- 15564877
TI  - The Arg389Gly beta1-adrenoceptor gene polymorphism determines contractile
      response to catecholamines.
AB  - OBJECTIVES: Recently, the Arg389Gly beta1-adrenoceptor (beta1AR) gene
      polymorphism has been detected. The Arg variant exhibited increased
      responsiveness to agonist-induced stimulation in vitro. Functional studies in
      isolated human atrial muscle strips and in-vivo studies revealed contradictory
      results regarding the functional relevance of this polymorphism. We sought to
      characterize the functional consequences of the Arg389Gly beta1-AR polymorphism
      in 30 consecutive healthy male volunteers in vivo. METHODS: beta1-AR genotype was
      determined by PCR and restriction analysis, which was confirmed by DNA
      sequencing. We compared heart rate, blood pressure, and contractile response of
      the various genotype carriers with a modified dobutamine stress echocardiography
      protocol. RESULTS: Subjects homozygous for the Arg389 beta1AR showed a
      significantly higher increase in fractional shortening upon cumulative doses of
      dobutamine as compared to subjects carrying one or two copies of the Gly389
      allele. A statistically significant difference was observed at a dobutamine dose
      of 10 microg/kg/min (46.5 +/- 1.3 vs. 41.8 +/- 1.0 %; P = 0.023) and was maximal
      at 40 microg/kg/min (61.9 +/- 1.4 vs. 52.8 +/- 1.6; P = 0.001). As a result, the
      systolic blood pressure response to dobutamine was significantly enhanced in
      individuals homozygous for the Arg389 allele, whereas the effect on heart rate
      did not differ between the two groups. Normalization for changing afterload
      conditions by calculating the pressure-dimension ratio revealed similar effects,
      indicating that the beta1AR-mediated effects are mainly a result of increased
      myocardial inotropy. CONCLUSION: These data indicate that the Arg389Gly beta1AR
      polymorphism is functionally relevant in vivo and determines contractile
      responsiveness to catecholamines in humans.

PMID- 15564878
TI  - The T341C (Ile114Thr) polymorphism of N-acetyltransferase 2 yields slow
      acetylator phenotype by enhanced protein degradation.
AB  - OBJECTIVES: Human N-acetyltransferase 2 (NAT2) plays a significant role in the
      clearance and biotransformation of many drugs and carcinogens. A TC (Ile114Thr)
      single nucleotide polymorphism (SNP) of NAT2 is commonly found in slow
      acetylators, leading to altered drug response and toxicity and possibly cancer
      susceptibility from carcinogens. The objective of this study was to investigate
      the mechanism by which this SNP causes slow acetylator phenotype. METHODS: A cDNA
      expression system was used to compare the NAT2*4 reference allele with an
      identical one possessing the TC SNP in COS-1 cells. The recombinant human NAT2
      enzymes were compared in regard to catalytic activity, kinetic parameters,
      thermostability, immunoreactive protein level, mRNA level and in-vivo protein
      degradation. RESULTS: The TC (Ile114Thr) SNP significantly reduced enzyme
      activity without changing the apparent kinetic parameters Km and Vmax (normalized
      for NAT2 protein), indicating that Ile114Thr did not change substrate or cofactor
      binding affinities or catalytic efficiency. Furthermore, no significant
      difference in NAT2 mRNA level was observed, indicating no impairment of
      transcription. The TC (Ile114Thr) SNP did not alter thermostability of NAT2 at
      either 37 or 50 degrees C. However, this SNP significantly reduced cytosolic NAT2
      immunoreactive protein through enhanced protein degradation. CONCLUSION: This is
      the first report indicating that protein degradation is an important mechanism of
      human NAT2 slow acetylator phenotype.

PMID- 15564879
TI  - Functionality of allelic variations in human alcohol dehydrogenase gene family:
      assessment of a functional window for protection against alcoholism.
AB  - Alcohol dehydrogenase (ADH) catalyses the rate-determining reaction in ethanol
      metabolism. Genetic association studies of diverse ethnic groups have firmly
      demonstrated that the allelic variant ADH1B*2 significantly protects against
      alcoholism but that ADH1C*1, which is in linkage with ADH1B*2, produces a
      negligible protection. The influence of other potential candidate genes/alleles
      within the human ADH family, ADH1B*3 and ADH2, remains unclear or controversial.
      To address this question, functionalities of ADH1B3 and ADH2 were assessed at a
      physiological level of coenzyme and substrate range. Ethanol-oxidizing activities
      of recombinant ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2 and ADH2 were determined at
      pH 7.5 in the presence of 0.5 mm NAD with 2-50 mm ethanol. The activity
      differences between ADH1B2 and ADH1B1 were taken as a threshold for effective
      protection against alcoholism and those between ADH1C1 and ADH1C2 as a threshold
      for null protection. Over 2-50 mm ethanol, the activities of ADH1B3 were found
      2.9-23-fold lower than those of ADH1B2, largely attributed to the Km effect
      (ADH1B2, 1.8 mm; ADH1B3, 61 mm). Strikingly, the ADH1B3 activity was only 84%
      that of ADH1B1 at a low ethanol concentration, 2 mm, but increased 10-fold at 50
      mm. Corrected for relative expression levels of the enzyme in liver, the hepatic
      ADH2 activities were estimated to be 18-97% those of ADH1B1 over 2-50 mm ethanol
      and were 28-140% of the activity differences between ADH1C1 and ADH1C2. The
      assessment based on the proposed functional window for the human ADH gene family
      indicates that ADH1B*3 may show some degree of protection against alcoholism and
      that the ADH2 functional variants appear to be negligible for this protection.

PMID- 15564880
TI  - Contribution of common polymorphisms in reduced folate carrier and gamma
      glutamylhydrolase to methotrexate polyglutamate levels in patients with
      rheumatoid arthritis.
AB  - We investigated whether polymorphisms in reduced folate carrier (SLC19A1 G80A)
      and gamma-glutamyl-hydrolase (GGH-401C/T) are predictive of methotrexate
      polyglutamate (MTXPG) levels in patients with rheumatoid arthritis treated with
      weekly low-dose methotrexate (MTX). Adult patients treated with MTX were enrolled
      in a multicentred study. Blood was drawn at the time of the visit, DNA was
      extracted and red blood cell (RBC) MTXPG levels (up to the penta-order of
      glutamation) were measured by high-performance liquid chromatography-fluorometry.
      A G80A polymorphism in SLC19A1 and a -401C/T promoter polymorphism in GGH were
      measured by polymerase chain reaction-restriction fragment length polymorphism.
      Multivariate linear and logistic regressions were used to predict long-chain RBC
      MTXPG3-5. In 226 adult patients receiving MTX (median 15 mg range: 5-25 mg)
      median RBC long-chain MTXPG3-5 was 56 nmol/l (range < 5-224 nmol/l). A total of
      35 patients carried the SLC19A1 80AA genotype whereas 36 patients carried the GGH
      401TT genotype. Weekly MTX dose, age, presence of the SLC19A1 80AA and GGH-401TT
      genotypes predicted independently and significantly MTXPG3-5 levels (global r =
      0.38; P < 0.0001). Patients with the GGH-401TT genotype were 4.8-fold [odds ratio
      (OR) 95% confidence interval (CI) 1.8-13.0; P = 0.002] more likely to have MTXPG3
      5 below the group median compared to patient carriers of the GGH-401CC or CT
      genotype. Conversely, those with the SLC19A1 80AA genotype were 3.4-fold more
      likely to have MTXPG3-5 levels above the group median compared to those with the
      SLC19A1 80GG or 80GA genotype (OR CI 95% 1.4-8.4; P = 0.007). These data
      demonstrate that polymorphisms in SLC19A1 and GGH affect polyglutamation of MTX.

PMID- 15564881
TI  - Complex haplotype structure of the human GNAS gene identifies a recombination
      hotspot centred on a single nucleotide polymorphism widely used in association
      studies.
AB  - The alpha subunit of the heterotrimeric G protein Gs (Gsalpha) is involved in
      numerous physiological processes and is a primary determinant of cellular
      responses to extracellular signals. Genetic variations in the Gsalpha gene may
      play an important role in complex diseases and drug responses. To characterize
      the genetic diversity in this locus, we resequenced exons and flanking introns of
      the gene in 44 genomic samples and analysed the haplotype structure of the gene
      in an additional 50 African-Americans and 50 Caucasians. Significant differences
      in allele frequency for nearly all the genotyped single nucleotide polymorphism
      (SNPs) were detected between the two ethnic groups. Linkage disequilibrium (LD)
      analysis of this locus revealed two haplotype blocks characterized by strong LD
      and reduced haplotype diversity, especially in Caucasians. Between the two blocks
      is a narrow (approximately 3 kb) recombination hotspot centred on exons 4 and 5,
      and a widely used genetic marker in association studies in this region (rs7121)
      was in linkage equilibrium with the rest of the gene. The haplotype structure of
      the GNAS locus warrants reevaluation of previous association studies that used
      marker rs7121 and affects choice of SNP markers to be used in future studies of
      this locus.

PMID- 15564882
TI  - Functional analysis of single nucleotide polymorphisms of hepatic organic anion
      transporter OATP1B1 (OATP-C).
AB  - OBJECTIVE: Two kinds of single nucleotide polymorphism (SNP; Asn130Asp and
      Val174Ala) are frequently observed in the liver specific transporter, organic
      anion transporting polypeptide 1B1 (OATP1B1/OATP-C) gene. Although these two SNPs
      occur independently in European-Americans, Val174Ala is mostly associated with
      Asn130Asp in Japanese. Our previous in-vivo studies in Japanese subjects
      indicated that the non-renal clearance of pravastatin was decreased to 13% of
      that in wild-type subjects (Nishizato et al. Clin Pharmacol Ther 2003;73(6):554
      564). The purpose of the present study is to characterize the function of SNPs
      variants of OATP1B1 in cDNA transfected cells. METHODS: The localization and
      transport activity were analyzed in HEK293 cells stably expressing wild-type
      OATP1B1 (OATP1B1*1a), OATP1B1*1b (Asn130Asp), OATP1B1*5 (Val174Ala) and
      OATP1B1*15 (Asn130Asp and Val174Ala). To characterize the intrinsic Vmax,
      observed Vmax in uptake study were normalized by the expression level estimated
      from Western blotting. RESULTS: All SNP variants are predominantly located on the
      cell surface. No significant alteration was observed in Km values for the
      transport of 17beta-estradiol 17beta-d-glucuronide (E217betaG), a typical
      substrate of OATP1B1, among these SNP variants. However, the normalized Vmax
      value for OATP1B1*15 was drastically decreased to less than 30% compared with
      OATP1B1*1a. In contrast, the transport activity of OATP1B1*1b (Asn130Asp) and
      OATP1B1*5 (Val 174Ala) was similar to that of OATP1B1*1a. CONCLUSIONS: These
      results are consistent with the results of our previous clinical studies. It is
      thus suggested that in-vivo disposition may be predicted from in-vitro results
      using recombinant transporters.

PMID- 15564883
TI  - Association between single nucleotide polymorphisms in deoxycytidine kinase and
      treatment response among acute myeloid leukaemia patients.
AB  - Development of resistance to 1-beta-arabinofuranosylcytosine (AraC) is a major
      obstacle in the treatment of patients with acute myeloid leukaemia (AML).
      Deficiency of functional deoxycytidine kinase (dCK) plays an important role in
      AraC resistance in vitro. We screened 5378 bp sequences of the dCK gene,
      including all exons and the 5' flanking region, and identified two single
      nucleotide polymorphisms (SNPs) in the regulatory region (rSNPs) with high allele
      frequencies. These two rSNPs (-201C>T and -360C>G) formed two major haplotypes.
      Genotyping with sequencing and MassARRAY system among 122 AML patients showed
      that those with -360CG/-201CT and -360GG/-201TT compound genotypes (n = 41)
      displayed a favourable response to chemotherapy whereas those with -360CC/-201CC
      (n = 81) tended to have a poor response (P = 0.025). Moreover, real-time
      quantitative reverse transcriptase-polymerase chain reaction showed that patients
      with -360CG/-201CT and -360GG/-201TT genotypes expressed higher level of dCK mRNA
      compared to those with the -360CC/-201CC genotype (P = 0.0034). Luciferase
      reporter assay showed that dCK 5' regulatory region bearing -360G/-201T genotype
      alone had an eight-fold greater transcriptional activation activity compared to
      that with -360C/-201C genotype, whereas co-transfection of both -360G/-201T and 
      360C/-201C constructs mimicked the heterozygous genotype, which exhibited a four
      fold greater activity compared to that with -360C/-201C. These results indicate
      that rSNP haplotypes of dCK gene may serve as a genetic marker for predicting
      drug responsiveness, which will be beneficial in establishing more effective AML
      chemotherapeutic regimens.

PMID- 15564884
TI  - Identification of non-functional allelic variant of CYP1A2 in dogs.
AB  - OBJECTIVES: Recently, we reported that AC-3933, a novel cognitive enhancer, is
      polymorphically hydroxylated in beagle dogs and that dogs could be phenotyped as
      extensive metabolizers (EM) or poor metabolizers (PM). AC-3933 polymorphic
      hydroxylation is caused by polymorphic expression of CYP1A2 protein in dog liver.
      METHODS: In order to clarify the mechanism of polymorphic expression of CYP1A2
      protein in beagle dogs, we investigated, in this study, the sequence of CYP1A2
      cDNA in EM and PM dogs. RESULTS: In PM dogs CYP1A2 gene, we discovered a nonsense
      mutation (C1117T) that induces a premature termination, and is associated with PM
      phenotype for AC-3933 hydroxylation. All PM dogs studied were homozygote of the
      mutant allele (m/m) and seemed to be CYP1A2-null phenotype as they lacked the
      heme-binding region in CYP1A2. These results indicate that the polymorphic
      expression of CYP1A2 protein observed in our previous study is caused by a single
      nucleotide polymorphism on CYP1A2 coding region. Furthermore, we developed a
      genotyping method for the mutant allele using a mismatch PCR-restriction fragment
      length polymorphism, and carried out frequency analysis in 149 beagle dogs.
      CONCLUSION: Our results indicate that more than 10% of the dogs studied were
      CYP1A2-null. Because CYP1A2-null phenotype in dogs affects the results of
      pharmacokinetic, toxicological and pharmacological studies of drug candidates,
      these findings are important in the pharmaceutical and the veterinary fields.

PMID- 15564885
TI  - Benzydamine metabolism in vivo is impaired in patients with deficiency of flavin
      containing monooxygenase 3.
AB  - Flavin-containing monooxygenase 3 (FMO3) is an important hepatic enzyme for the
      detoxification of xenobiotics. The pharmacogenetic relevance of FMO3 deficiency
      has frequently been postulated from in vitro studies but has not yet been proven
      in vivo. We investigated the metabolism of benzydamine (BZD) in controls as well
      as patients with severe FMO3 deficiency and found evidence of markedly reduced N
      oxygenation capacity both in serum and urine samples. After 2 h the N-oxide/total
      BZD ratio in serum of the patients ranged from 3.1 to 5.6% compared to controls
      with a median of 13.1%. Urinary BZD was almost fully N-oxygenated in controls (>
      93.7%) whilst the urinary N-oxide/total BZD ratios were 29.4-35.7% in patients.
      Our study is the first to confirm that severe FMO3 deficiency is associated with
      reduced metabolism of a drug substrate in vivo. This is relevant because of the
      prevalence of mild FMO3 deficiency in the general population. BZD may be also
      useful as a diagnostic probe for determination of FMO3 deficiency in vivo.

PMID- 15564886
TI  - Lack of association between the ITPA 94C>A polymorphism and adverse effects from
      azathioprine.
AB  - A 94C>A missense mutation in the ITPA gene which encodes inosine triphosphate
      pyrophosphatase has been associated with adverse effects from azathioprine,
      specifically flu-like symptoms, pancreatitis and rash. We hypothesized that this
      association may also be present in a larger, population-based group of
      inflammatory bowel disease patients intolerant of thiopurine drugs. We performed
      genotyping for this polymorphism and TPMT*2 and TPMT*3 in 73 such patients and 74
      patients with inflammatory bowel disease who have tolerated azathioprine. We
      could not demonstrate a significant association between the ITPA94C>A genotype
      and any adverse effects (Odds ratio (OR) 1.015, 95% confidence interval (CI)
      0.360-2.867, P = 0.593), flu-like symptoms (OR 1.547, 95%CI 0.368-6.496, P =
      0.398), rash (no ITPA 94C>A polymorphism identified) or pancreatitis (no ITPA
      94C>A polymorphism identified). We found no significant association between the
      ITPA 94C>A polymorphism and adverse effects to thiopurine drugs.

PMID- 15564887
TI  - HLA-B*5701 and abacavir hypersensitivity.

PMID- 15564889
TI  - Molecular psychiatry meeting, February 2003, Lake Louise, Canada.
AB  - The 10th Annual Molecular Psychiatry Conference was held in Lake Louise, Canada
      on 23-25 February 2003. The host was Bill Byerley (University of California,
      Irvine, California, USA), and the meeting was supported by Janssen Pharmaceutica
      and the Department of Psychiatry, University of California, Irvine, California,
      USA.

PMID- 15564890
TI  - Evaluation of genetic substructure in the Irish Study of High-Density
      Schizophrenia Families.
AB  - The presence of genetic substructure has the potential to diminish the chances of
      detecting a linkage signal. Using a Markov chain Monte Carlo procedure developed
      by Pritchard and colleagues and implemented in the program STRUCTURE, we
      evaluated the evidence for genetic substructure using genotypes from 37
      microsatellite markers in affected individuals selected at random from 263
      multiplex families in the Irish Study of High-Density Schizophrenia Families. We
      found no evidence for the presence of genetic substructure in this sample.

PMID- 15564891
TI  - Single nucleotide polymorphisms in the leptin receptor gene: studies in anorexia
      nervosa.
AB  - Anorexia nervosa is an eating disorder of unknown aetiology. There is significant
      evidence for a genetic component in the pathogenesis of this disorder. A region
      on chromosome 1 has been identified as a susceptibility locus. The leptin
      receptor has been mapped to a similar region, further upstream of this
      susceptibility locus. Leptin and its receptor are known to be important factors
      in the control and regulation of body weight. Single nucleotide polymorphisms
      (SNPs) in the leptin receptor are associated with measures of body weight. In the
      present study, SNPs in the coding region of the leptin receptor were analysed and
      their possible association with anorexia nervosa was investigated. Two cohorts of
      young women, 176 Caucasian anorexia nervosa patients and 152 normal Caucasian
      females, were genotyped for three SNPs in the leptin receptor. There was no
      significant difference in allele or genotype frequency, for any SNP, between the
      normal controls and the cohort of anorexia subjects. There were no significant
      associations with any genotype and body mass index in either the control or
      anorexic cohorts. When the anorexic cohort was subdivided into restricting and
      bingeing/purging behaviours, we found no significant association with any
      genotype. Analysis of haplotypes showed no significant evidence of association
      with anorexia. In summary, leptin receptor SNPs do not appear to be important
      factors in the regulation of body weight in young, pre-menopausal women or have
      any significant association with anorexia nervosa.

PMID- 15564892
TI  - The serotonin-2A receptor polymorphism and smoking behavior in Japan.
AB  - Epidemiological and genetic studies on smoking behavior have been performed, and
      in this study the human serotonin 2A receptor (HTR2A) polymorphism was examined
      in 82 smoking behaviorists and 125 healthy controls. HTR2A consists of at least
      14 subtypes, depression and anxiety occur due to agonists, and hallucination,
      fever heat, psychomotor excitement and other symptoms also occur. The
      polymorphism in HTR2A (102T/C, -1438A/G) was identified by means of the
      polymerase chain reaction followed by restriction fragment length polymorphism,
      and the Fagerstrom Test for Nicotine Dependence was used to determine the extent
      of smoking behavior. The results suggest that the HTR2A (102T/C, -1438G/A)
      polymorphism might not be associated with susceptibility to a risk factor for
      developing smoking behavior. Further studies are required to determine whether or
      not the novel serotonin receptor (5-HTR) polymorphism reflects the pathogenesis
      of smoking behavior.

PMID- 15564893
TI  - Psychiatric findings in four female carriers of Fabry disease.
AB  - Anderson-Fabry disease (AFD) is an X-linked recessive disorder of
      glycosphingolipid metabolism. Most female carriers are clinically symptomatic;
      however, psychiatric diagnoses have not been reported in this population. We
      describe four female carriers of AFD disease who met DSM-IV criteria for major
      depression. All cases had a score above 26 on the Hamilton Rating Scale for
      Depression, indicating severe depression. This was independent of the severity or
      number of symptoms of AFD disease. Excessive guilt, fatigue, occupational
      difficulty, suicidal ideation and depressed mood were findings in all cases. In
      conclusion, the common presence of depression in carriers of AFD implies the need
      for a multidisciplinary approach, including psychiatry, in management of these
      patients. Further studies are recommended to establish the etiology of
      psychiatric complications, as well as the incidence and the response to
      pharmacotherapy and psychotherapy.

PMID- 15564894
TI  - Association analysis between a functional polymorphism in the monoamine oxidase A
      gene promoter and severe mood disorders.
AB  - Monoamine oxidase A (MAOA) has been suggested to be involved in human behaviour
      and physiology due to its key role in the metabolism of several different
      biological amines including the neurotransmitters serotonin, norepinephrin and
      dopamine.Recently, a 30 bp repeat in the MAOA gene promoter (uMAOA) has been
      demonstrated to be polymorphic and to affect transcriptional activity. In the
      context of an association case-control study design, we analysed the uMAOA
      polymorphism in 389 unrelated patients affected by severe mood disorders (88
      bipolar subjects and 301 major depressive individuals) and in 156 controls. No
      association was found between the uMAOA locus and bipolar disorder or major
      depression. However, an increase of high-activity uMAOA alleles was found in
      major depression female patients presenting a seasonal pattern (chi2=3.013,
      P=0.05) or psychotic symptoms in their episodes (chi2=2.679, P=0.07). In female
      bipolar disorder patients, long alleles were associated with longest times of
      admission (F=4.604, P=0.037). A trend for association with seasonal pattern was
      also defined in this group (data not corrected for multiple testing). Our results
      suggest that MAOA gene variation may modulate the expression of some clinical
      aspects of severe mood disorders, especially in females, and support the
      existence of a genetic and aetiologic heterogeneity underlying the diagnoses of
      bipolar disorder and major depression.

PMID- 15564895
TI  - Genetic association analysis of functional polymorphisms in the cytochrome P450
      1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with
      schizophrenia.
AB  - OBJECTIVE: Recent studies have revealed positive associations between tardive
      dyskinesia (TD) and genetic polymorphisms of several cytochrome P450 (CYP)
      subfamilies that are involved in pharmacokinetic process of antipsychotic drugs.
      In the present study, we analyzed the relationship between TD and two
      polymorphisms of the CYP1A2 gene, 734C/A and -2964G/A, in a sample of Japanese
      patients with schizophrenia. METHODS: We studied 199 Japanese patients with
      schizophrenia. We used the Abnormal Involuntary Movement Scale to evaluate TD.
      Two polymorphisms of the CYP1A2 gene, 734C/A and -2964 G/A were genotyped by
      means of polymerase chain reaction and restriction fragment length polymorphism
      analysis. RESULTS: Neither the 734C/A nor the -2964G/A polymorphism was
      associated with TD [734C/A genotype: chi2=0.02, degrees of freedom (df)=2,
      P=1.00; allele: chi2=0.02, df=1, P=0.89; -2964G/A genotype: chi2=0.21, df=2,
      P=0.90; allele: chi2=0.15, df=1, P=0.70]. In addition, CYP1A2 haplotype was
      associated with TD (chi2=0.24, df=3, P=0.97). Furthermore, in both the subgroup
      of smokers and the subgroup of patients receiving high-dosage antipsychotics
      (chlorpromazine equivalent >1000 mg), neither the 734C/A nor the -2964G/A
      polymorphism was associated with TD. CONCLUSIONS: We did not find significant
      associations between the 734C/A and -2964G/A polymorphisms of CYP1A2 gene and TD
      in Japanese patients with schizophrenia. Our results suggest that these CYP1A2
      gene polymorphisms may not contribute to TD susceptibility.

PMID- 15564896
TI  - Uncoupling protein-2/uncoupling protein-3 gene polymorphism is not associated
      with anorexia nervosa.
AB  - Energy expenditure abnormalities have been observed in anorexia nervosa (AN). The
      uncoupling proteins (UCPs) have been implicated as having a role in energy
      metabolism and thermogenesis, and an association between a marker flanking the
      UCP-2/UCP-3 gene cluster and AN has been reported. Also known are
      insertion/deletion and -866G/A polymorphisms in the UCP-2 gene, and the -55C/T
      polymorphism in the UCP-3 gene. Differences in these alleles are reportedly
      related to changes in energy expenditure, body mass index, fat tissue
      accumulation and obesity. Therefore, this case-control association analysis was
      done to determine whether any of these UCP-2/3 gene polymorphisms are related to
      a predisposition to AN. In analysis of a cohort of 106 female Japanese AN
      sufferers and 126 normal female controls, we found no between-group differences
      in the polymorphism frequencies of these groups. The hypothesis that differences
      in the UCP-2/3 gene influence the susceptibility to AN was not supported.

PMID- 15564897
TI  - Association analysis between Tourette's syndrome and dopamine D1 receptor gene in
      Taiwanese children.
AB  - OBJECTIVE: Recent research suggests that Tourette's syndrome (TS) may result from
      a defect in the dopamine system. The dopamine 1 receptor (DRD1) gene is a
      candidate gene in the study of the etiology of neuropsychiatric diseases that may
      involve dopaminergic abnormalities. We sought to test the hypothesis that the
      DRD1 gene might play a role in TS. METHODS: By performing an association study,
      we collected an independent sample of patients from the midland region of Taiwan
      and investigated whether DRD1 gene polymorphisms can be used as markers of
      susceptibility to TS. A total of 148 children with TS and 83 normal control
      subjects were included in the study. A polymerase chain reaction was used to
      identify the A/G polymorphism of the DRD1 gene. Genotypes and allelic frequencies
      for the DRD1 gene polymorphisms in both groups were compared. RESULTS: The
      results showed that genotypes and allelic frequencies for the DRD1 gene
      polymorphisms in both groups were not significantly different. CONCLUSION: These
      data suggest that DRD1 gene may not be a useful marker for prediction of the
      susceptibility of TS.

PMID- 15564898
TI  - Association analysis of dopamine D2-like receptor genes and methamphetamine
      abuse.
AB  - OBJECTIVES: Substance use disorders are familial, and genetic factors explain a
      substantial degree of their familial aggregation. This study employs an
      association approach to examine the genetic underpinning of methamphetamine
      (MAMP) use and MAMP-induced psychosis. METHODS: A total of 416 MAMP abusers from
      a hospital and a detention center in Taipei were interviewed with the Diagnostic
      Interview for Genetic Study and the Family Interview for Genetic Study. Genetic
      polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly,
      and DRD4 exon III variable number of tandem repeats, were compared between: (a)
      MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with
      MAMP-induced psychosis and the 252 MAMP users with no psychosis. RESULTS: None of
      the three markers we studied were associated with predisposition to psychosis
      among the MAMP abusers. The MAMP abusers had a higher (P=0.011) prevalence of the
      seven-repeat allele of DRD4 than normal controls. CONCLUSIONS: Chance
      fluctuations in the frequency of rare alleles and ascertainment differences in
      the case and control samples cannot be ruled out. Therefore, further studies of
      the seven-repeat allele in MAMP abusers and controls should be performed before
      an association can be established.

PMID- 15564899
TI  - Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant
      in schizophrenia and mood disorders.
AB  - OBJECTIVE: An elevated homocysteine level has been reported for patients with
      schizophrenia and depression. We investigated the frequency of the common C667 T
      variant of the enzyme methylenetetrahydrofolate reductase in controls and
      patients of Chinese descent. METHODS: Controls with no history of mental disorder
      and patients diagnosed with schizophrenia, bipolar and unipolar disorders were
      recruited. Genomic DNA from all were genotyped for the C667 T polymorphism by
      polymerase chain reaction-restriction fragment length polymorphism. RESULTS:
      There was no significant difference in genotype distributions or allele
      frequencies between controls and any of the diagnostic groups, although the
      frequency of the T allele was higher for all diagnostic groups and for both the
      male and female genders. When data was analyzed with the minor T allele as
      dominant, there was an excess of the T-containing genotypes in each of the
      patient groups compared with controls. For the difference between controls and
      all cases combined it almost reached statistical significance (P=0.077), with an
      odds ratio of 1.46 (95% confidence interval, 0.96-2.22). CONCLUSIONS: Although
      there was no significant association as measured by the P value, the odds ratio
      and confidence interval provided some evidence of increased risk for individuals
      with the T-containing genotypes. A minor role for this polymorphism in the
      pathogenesis of schizophrenia and depression could not be ruled out and would
      warrant further investigation.

PMID- 15564900
TI  - Systematic screening for mutations in the human N-methyl-D-aspartate receptor 1
      gene in schizophrenic patients from the German population.
AB  - Evidence for a dysfunction of the N-methyl-D-aspartate (NMDA) type of ionotropic
      glutamate receptors in schizophrenic patients, comes from neurochemical and
      clinical pharmacologic data. Therefore, the NMDAR1 gene can be regarded as an
      interesting candidate gene for schizophrenia. Several groups have tried to
      identify variants of this gene in schizophrenic patients in different, however
      not in German, populations. We sought to identify sequence changes of potential
      functional relevance in genomic DNA from 46 German unrelated schizophrenic
      patients by means of single-strand conformation analysis. No mutations of likely
      functional relevance were observed. We identified two synonymous coding Single
      Nucleotide Polymorphisms (cSNPs) in exons 6 and 7, and two SNPs in exon-flanking
      intronic sequences. Genotype distribution of these four SNPs was not
      significantly different between schizophrenic patients and controls. Our results
      suggest that the NMDAR1 subunit is not frequently involved in the development of
      schizophrenia in the German population.

PMID- 15564901
TI  - Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants for
      back pain in the United States.
AB  - STUDY DESIGN: Secondary analysis of the 2000 Medical Expenditure Panel Survey
      (MEPS). OBJECTIVE.: To examine national prescription patterns of nonsteroidal
      anti-inflammatory drugs (NSAIDs) and muscle relaxants among individuals with back
      pain in the United States. SUMMARY OF BACKGROUND DATA: There is a lack of
      information on national prescription patterns of NSAIDs and muscle relaxants
      among individuals with back pain in the United States. METHODS: Traditional
      NSAIDs, cyclooxygenase-2-specific (COX-2) inhibitors, and muscle relaxants were
      investigated. Individuals with back pain were stratified by socio-demographic
      characteristics and geographic regions. For each medication category, overall
      prescribing frequency was compared across different strata and individual drug
      prescription was analyzed. RESULTS: Traditional NSAIDs, COX-2 inhibitors, and
      muscle relaxants, respectively, accounted for 16.3%, 10%, and 18.5% of total
      prescriptions for back pain in 2000. Among individual drugs, ibuprofen and
      naproxen accounted for most of the prescriptions for traditional NSAIDs (60%),
      whereas two thirds of the prescriptions for muscle relaxants were attributable to
      cyclobenzaprine, carisoprodol, and methocarbamol. Prescription of COX-2
      inhibitors or muscle relaxants demonstrated wide variations across different
      regions. Several individual characteristics including age, race, and educational
      level were associated with the prescription of some of the medications.
      CONCLUSIONS: Neither traditional NSAIDs, nor COX-2 inhibitors, nor muscle
      relaxants dominated prescriptions for back pain. However, a small number of
      individual drugs were attributable to most of the prescriptions for traditional
      NSAIDs or muscle relaxants. The prescription of some of the medications
      demonstrated wide variations across different regions or different racial and
      educational groups. More studies are needed to understand the source of the
      variations and what constitutes optimal prescribing.

PMID- 15564902
TI  - Myelopathic presentation of cervical juxtafacet cyst: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVES: Discussion about the nature of the lesion,
      its various presentations, image characteristics, clinical features, surgical
      treatment, and patient outcome. SUMMARY OF BACKGROUND DATA: Juxtafacet cysts are
      uncommon intraspinal lesions most frequently found in the lumbar region. They
      usually originate as monoradicular compression syndrome mimicking disc
      herniation. In the cervical spine, they are rare and also have similar clinical
      features to intervertebral disc protrusion. However, the image findings are
      highly discriminative and often lead to accurate diagnosis. The cyst occupies a
      posterolateral position within the spinal canal, displacing the nerve root
      anteriorly. This situation is better seen in magnetic resonance imaging, but
      computed tomography scan and plain myelography also point to a diagnosis. The
      posterolateral site in the spinal canal can be accessed directly by a single
      level laminectomy or hemilaminectomy. These are epidural lesions, usually cystic,
      attached to the facet joint and protruding into the intervertebral foramen.
      Recurrence after surgery is extremely rare and has only been reported in the
      lumbar spine. METHODS: In this article, we report the case of a male patient, 64
      years of age, who presented with a progressive and severe myelopathy associated
      with multiple mononeuropathy, which delayed the diagnosis and treatment of the
      main neurologic condition, a cervical spinal compressive syndrome, proven to have
      originated as a juxtafacet cyst. The patient underwent complete surgical excision
      of the lesion. RESULTS AND CONCLUSIONS: The patient had good recovery of the
      myelopathy, and 6 months after surgery, he was able to walk. A follow-up of 2.5
      years has not revealed any recurrence or new neurologic conditions.

PMID- 15564903
TI  - Epidural abscess and discitis complicating instrumented posterior lumbar
      interbody fusion: a case report.
AB  - STUDY DESIGN: A case of epidural abscess and discitis following instrumented PLIF
      using a single carbon fiber interbody cage is presented. OBJECTIVE: To describe a
      previously unreported complication of epidural abscess and discitis following
      posterior lumbar interbody fusion using a single carbon fiber cage. SUMMARY OF
      BACKGROUND DATA: Various complications have been reported with PLIF. These
      include graft migration, pseudarthrosis, implant subsidence, epidural hemorrhage,
      incidental durotomy, arachnoiditis, transient or permanent neurologic deficits,
      persistence of pain, and wound infections. There are no reported cases of
      epidural abscess or refractory discitis associated with PLIF. METHODS: A 35-year
      old infantryman on active duty with chronic low back pain and single-level lumbar
      disc degeneration underwent instrumented PLIF after reporting no improvement with
      3 years of extension-based physical therapy and nonsteroidal pain medications.
      His back pain was reported improved at 6 weeks after surgery. At 12 weeks after
      surgery, he presented to the emergency department with intense back pain and
      fevers. Laboratory data were remarkable for elevated erythrocyte sedimentation
      rate (118) and C-reactive protein (38). Initial imaging studies, including a
      lumbar MRI, did not demonstrate any abnormalities. The patient continued to spike
      fevers, and a repeat lumbar MRI 1 week later clearly demonstrated the presence of
      an epidural abscess at the level of the PLIF surgery. The patient was treated
      with surgical debridement and epidural abscess drainage. The interbody cage was
      left in place. Surgical cultures identified Staphylococcus aureus as the
      pathogen, and the patient was placed on intravenous vancomycin. During the
      ensuing 3 weeks, his clinical symptoms worsened and his radiographs demonstrated
      lucency in the region of his interbody cage. Repeat debridement was performed,
      and his interbody cage and pedicle screw instrumentation were removed 4 months
      after initial surgery. RESULTS: The disc space infection resolved following
      removal of the implants. Radiographs at 6 months after instrumentation removal
      demonstrated solid bilateral posterolateral arthrodesis. The patient returned to
      active duty 1 year after his initial surgery, reporting that his back pain was
      reduced compared with his preoperative level. CONCLUSIONS: There is a paucity of
      literature on epidural abscess and discitis as complications associated with
      PLIF. In this case, the infection persisted despite surgical debridement and
      intravenous antibiotics. The patient ultimately required removal of the interbody
      implant and posterior instrumentation. The patient developed solid posterolateral
      arthrodesis despite the presence of deep infection, which led to early implant
      removal 4 months after the initial surgery. This case underscores the potential
      importance of concomitant posterolateral fusion, particularly following wide
      laminectomy and facetectomy required for PLIF.

PMID- 15564904
TI  - Solitary fibrous tumor in the occipitocervical region: a case report.
AB  - STUDY DESIGN: Case report of a solitary fibrous tumor in the occipitocervical
      region. OBJECTIVE: To describe a rare clinical entity and successful management
      in a patient with solitary fibrous tumor in the occipitocervical region. SUMMARY
      OF BACKGROUND DATA: Solitary fibrous tumor is a rare spindle cell neoplasm of
      adults that arises most commonly in the pleura. Recently, this tumor has been
      reported in a number of other sites. However, its occurrence in the
      occipitocervical region is rare. METHODS: The patient presented with a painless
      mass in the left posterior neck. Resection of the tumor was performed. RESULTS:
      Histopathological study revealed features of a solitary fibrous tumor. Clinical
      follow-up review for 2.5 years shows no evidence of recurrence or metastasis.
      CONCLUSION: A case of extrapleural solitary fibrous tumor in the occipitocervical
      region was reported. Solitary fibrous tumor should be considered in the
      differential diagnosis in a tumoral mass of this region.

PMID- 15564905
TI  - Fenestration of vertebral artery at the craniovertebral junction in Down
      syndrome: a case report.
AB  - STUDY DESIGN: Case report of a Down syndrome patient with right vertebral artery
      fenestration and abnormalities of the craniovertebral junction. OBJECTIVES:
      Describe the utility of 3-dimensional computed tomography angiography for
      evaluating vertebral artery anomalies before surgery. SUMMARY OF BACKGROUND DATA:
      Previous reviews evaluating catheter angiograms identified various anomalies of
      vertebral artery at the craniovertebral junction. The frequency of vertebral
      artery anomalies is increased in patients having osseous anomalies at the
      craniovertebral junction. Down syndrome is associated with a high incidence of
      bone abnormalities at the craniovertebral junction, but there have been no
      published reports of vertebral artery anomalies per se at the craniovertebral
      junction. METHODS: A 16-year-old woman with trisomy 21 presented with gait
      abnormalities and myelopathy in association with bone abnormalities at the
      craniovertebral junction, including hypoplastic odontoid and ossiculum terminale.
      Computed tomography angiography showed that right vertebral artery bifurcated
      after exiting the C2 transverse foramen with one branch passing through the C1
      transverse foramen, whereas the other turned posteromedially and entered the
      spinal canal between C1 and C2. RESULTS: Occipito-C2 posterior fusion was
      performed with a rod and screw system. Intraoperatively, the course of the
      anomalous right vertebral artery was identified by Doppler angiography, and the
      surgical approach was modified to allow safe pedicle screw insertion while
      avoiding vertebral artery injury. After surgery, myelopathy resolved within 3
      months. CONCLUSIONS: Before corrective surgery of craniovertebral junction
      anomalies in patients with Down syndrome, the possibility of vertebral artery
      anomalies associated with abnormal craniovertebral junction anatomy should be
      considered. With preoperative 3-dimensional computed tomography angiography, we
      can precisely identify the anomalous vertebral artery and modify the surgical
      approach to reduce the possible risk of intraoperative vertebral artery injury in
      advance.

PMID- 15564907
TI  - Does it matter which exercise? A randomized control trial of exercise for low
      back pain.
AB  - STUDY DESIGN: Multicentered randomized controlled trial. OBJECTIVES: To determine
      if previously validated low back pain (LBP) subgroups respond differently to
      contrasting exercise prescriptions. SUMMARY OF BACKGROUND DATA: The role of
      "patient-specific" exercises in managing LBP is controversial. METHODS: A total
      of 312 acute, subacute, and chronic patients, including LBP-only and sciatica,
      underwent a standardized mechanical assessment classifying them by their pain
      response, specifically eliciting either a "directional preference" (DP) (i.e., an
      immediate, lasting improvement in pain from performing either repeated lumbar
      flexion, extension, or sideglide/rotation tests), or no DP. Only DP subjects were
      randomized to: 1) directional exercises "matching" their preferred direction
      (DP), 2) exercises directionally "opposite" their DP, or 3) "nondirectional"
      exercises. Outcome measures included pain intensity, location, disability,
      medication use, degree of recovery, depression, and work interference. RESULTS: A
      DP was elicited in 74% (230) of subjects. One third of both the opposite and non
      directionally treated subjects withdrew within 2 weeks because of no improvement
      or worsening (no matched subject withdrew). Significantly greater improvements
      occurred in matched subjects compared with both other treatment groups in every
      outcome (P values <0.001), including a threefold decrease in medication use.
      CONCLUSIONS: Consistent with prior evidence, a standardized mechanical assessment
      identified a large subgroup of LBP patients with a DP. Regardless of subjects'
      direction of preference, the response to contrasting exercise prescriptions was
      significantly different: exercises matching subjects' DP significantly and
      rapidly decreased pain and medication use and improved in all other outcomes. If
      repeatable, such subgroup validation has important implications for LBP
      management.

PMID- 15564908
TI  - ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of
      proteoglycans and BMPs in vitro and in vivo.
AB  - STUDY DESIGN: Experiments using both in vitro tissue culture and in vivo rabbit
      methods were used to study the effect of Lim Mineralization Protein-1 (LMP-1) on
      intervertebral disc (IVD) cell production of proteoglycans and bone morphogenetic
      proteins (BMPs). OBJECTIVES: To determine the effect of LMP-1 overexpression in
      IVD cells on the production of proteoglycans and BMPs both in vitro and in vivo
      and to show that LMP-1 mediates the control of proteoglycan production through
      its action on BMPs. SUMMARY OF BACKGROUND DATA: Because BMPs are known to
      increase proteoglycan synthesis and LMP-1 is known to upregulate BMPs in certain
      cells, it was hypothesized that LMP-1 may increase proteoglycan production in IVD
      cells. METHODS: DMMB, real-time polymerase chain reaction, and ELISA methods were
      used to quantitate proteoglycan, mRNA, and protein levels, respectively. Noggin
      was used to block the effect of the adenovirus carrying LMP-1 (AdLMP-1) on
      proteoglycan synthesis. In vivo experiments using intradiscal AdLMP-1 injection
      were performed with New Zealand White rabbits. Three weeks later, the mRNA levels
      of LMP-1, aggrecan, BMP-2, and BMP-7 were measured. RESULTS: In vitro experiments
      revealed that the sulfated glycosaminoglycan (sGAG) and aggrecan mRNA levels were
      significantly increased with AdLMP-1 treatment. Similarly, BMP-2 and BMP-7 mRNA
      and protein levels increased significantly, but BMP-4 and BMP-6 levels were
      unchanged. Noggin blocked the upregulation of proteoglycan by AdLMP-1. In vivo
      discs injected with AdLMP-1 had significantly elevated levels of LMP-1, BMP-2,
      and BMP-7 mRNA. CONCLUSIONS: LMP-1 overexpression increases disc cell production
      of proteoglycan, BMP-2, and BMP-7. LMP-1 mediates the control of proteoglycan
      production through its action on BMP.

PMID- 15564909
TI  - ISSLS prize winner: Collagen fibril sliding governs cell mechanics in the anulus
      fibrosus: an in situ confocal microscopy study of bovine discs.
AB  - STUDY DESIGN: In situ investigation of collagen and cell mechanics in bovine
      caudal discs using novel techniques of confocal microscopy. OBJECTIVE: To measure
      simultaneously the in situ intercellular and collagen matrix mechanics in the
      inner and outer anulus fibrosus of the intervertebral disc subjected to flexion.
      SUMMARY OF BACKGROUND DATA: Mechanobiology studies, both in vivo and in vitro,
      clearly demonstrate that mechanical factors can influence the metabolic activity
      of disc cells, altering the expression of key extracellular matrix molecules.
      Essential to elucidating the mechanotransduction mechanisms is a detailed
      understanding of the in situ mechanical environment of disc cells in response to
      whole-body mechanical loads. METHODS: Confocal microscopy was used to
      simultaneously track and capture in situ images of fluorescently labeled cells
      and matrix during an applied flexion. The position of the nuclear centroids was
      calculated before and after applied flexion to quantify the in situ intercellular
      mechanics of both lamellar and interlamellar cells. The deflection patterns of
      lines photobleached into the extracellular matrix were used to quantify collagen
      fibril sliding and collagen fibril strains in situ. RESULTS: The extracellular
      matrix was observed to deflect nonuniformly due to the relative sliding of the
      collagen fibrils. Intercellular displacements within the lamellar layers were
      also nonuniform, both along a cell row and between adjacent rows. Within a cell
      row, the intercellular displacements were small (<1%). CONCLUSIONS: The in situ
      cell mechanics of anular cells was found to be strongly influenced by collagen
      fibril sliding in the extracellular matrix and could not be inferred directly
      from applied tissue loads.

PMID- 15564910
TI  - Disc inflammation potentially promotes axonal regeneration of dorsal root
      ganglion neurons innervating lumbar intervertebral disc in rats.
AB  - STUDY DESIGN: The expression of growth-associated protein 43 (GAP-43), a marker
      of axonal growth, in the dorsal root ganglion (DRG) neurons innervating the
      lumbar intervertebral disc was assessed using the retrograde tracing method and
      immunohistochemistry. OBJECTIVES: To study whether disc inflammation affects GAP
      43 expression in DRG neurons innervating the disc in rats. SUMMARY AND BACKGROUND
      DATA: Persistent inflammation and nerve ingrowth into the inner layer of
      degenerated discs can be a cause of discogenic pain. Although the presence of GAP
      43-expressing nerve fibers in painful discs has been reported, the expression of
      GAP-43 in DRG neurons innervating the disc has not been studied. METHODS: Seven
      days after the application of Fluoro-Gold to the L5-L6 disc, 50 microL of saline
      (n = 10, control group) or complete Freund's adjuvant (n = 10, inflammatory
      group) was applied to the disc in rats. Ten days after the Fluoro-Gold
      application, T13-L5 DRGs were double-stained with GAP-43 and either calcitonin
      gene-related peptide or isolectin B4 (IB4). RESULTS: The percentage of Fluoro
      Gold-labeled neurons that were positive for GAP-43 was significantly higher in
      the inflammatory group (44%) than in the control group (24%, P < 0.001). In both
      groups, the majority of GAP-43-positive neurons were small and positive for
      calcitonin gene-related peptide but not IB4. CONCLUSIONS: The present results
      suggest that disc inflammation potentially promotes axonal growth of DRG neurons
      innervating the disc. In light of the strong correlation between the expression
      of calcitonin gene-related peptide and nerve growth factor receptor, it is most
      likely that nerve growth factor-sensitive DRG neurons extend their axons
      following disc inflammation.

PMID- 15564911
TI  - Differentiation of mesenchymal stem cells towards a nucleus pulposus-like
      phenotype in vitro: implications for cell-based transplantation therapy.
AB  - OBJECTIVE: Because mesenchymal stem cells can differentiate into chondrocyte-like
      cells, we ask the question, can mesenchymal stem cells commit to the nucleus
      pulposus phenotype? BACKGROUND: Back pain, a significant source of morbidity in
      our society, is linked to degenerative changes of the intervertebral disc.
      Absence of suitable graft tissue limits therapeutic approaches for repair of disc
      tissue. For this reason, there is considerable interest in developing "tissue
      engineering" strategies for the regeneration of the nucleus pulposus. METHODS:
      Rat mesenchymal stem cells were immobilized in 3-dimensional alginate hydrogels
      and cultured in a medium containing transforming growth factor-beta1 under
      hypoxia (2% O2) and normoxia (20% O2). Mesenchymal stem cells were examined by
      confocal microscopy to evaluate their viability and metabolic status after
      labeling with Celltracker green, a thiol sensitive dye, and Mitotracker red, a
      dye sensitive to the mitochondrial membrane potential. Flow cytometry,
      semiquantitative reverse transcription polymerase chain reaction and Western blot
      analysis were carried out to evaluate phenotypic and biosynthetic activities and
      the signaling pathways involved in the differentiation process. RESULTS: Under
      hypoxic conditions, mesenchymal stem cells formed large aggregates and exhibited
      positive Celltracker and Mitotracker signals. Glucose transporter-3, matrix
      metalloproteinase-2, collagen type II and type XI, and aggrecan mRNA and protein
      expression was upregulated, whereas there was no change in the levels of decorin,
      biglycan, fibromodulin, and lumican. Hypoxia maintained the expression of CD44
      (hyaluronan receptor), ALCAM (CD166), and endoglin (transforming growth factor
      beta receptor). Likewise, expression of beta3 and alpha2 integrin was
      upregulated. Transforming growth factor-beta treatment increased MAPK activity
      and Sox-9, aggrecan, and collagen type II gene expression. Basal levels of the
      phosphorylated MAPK isoform ERK1/2, but not p38, were higher under hypoxic
      conditions than normoxia, and its activation was further augmented by treatment
      of cells with transforming growth factor-beta. In hypoxia, transforming growth
      factor-beta sustained phosphorylated p38 expression for an extended time period.
      Pharmacological inhibition of ERK1/2 and p38 enzymatic activity resulted in a
      decrease in Sox-9, aggrecan, and collagen type II mRNA levels. CONCLUSIONS: Our
      results indicate that hypoxia and transforming growth factor-beta drive
      mesenchymal stem cell differentiation towards a phenotype consistent with that of
      the nucleus pulposus. Measurement of selected signaling molecules and response to
      specific inhibitors suggest involvement of MAPK signaling pathways. It is
      concluded that mesenchymal stem cells could be used to repopulate the damaged or
      degenerate intervertebral disc.

PMID- 15564912
TI  - Muscle activity, internal loads, and stability of the human spine in standing
      postures: combined model and in vivo studies.
AB  - STUDY DESIGN: The load in active and passive spinal components as well as the
      stability margin in standing postures +/- load in hands are studied using both
      computational model and in vivo studies. OBJECTIVE: To investigate muscle
      activity, spinal loads, and system stability in standing postures. SUMMARY OF
      BACKGROUND DATA: Study of the human trunk yields a redundant system, the
      satisfactory solution of which remains yet to be done. Existing biomechanical
      models are often oversimplified or attempt to solve the problem by equilibrium of
      loads at only one cross section along the spine. METHODS: In vivo measurements
      are performed to obtain kinematics (by skin markers) as input data into model and
      EMG activity (by surface electrodes) for validation of predictions. A
      thoracolumbar model, while accounting for nonlinear ligamentous properties and
      trunk musculature, solved the redundant active-passive system by a novel
      kinematics-based approach that used both the posture and gravity/external loads
      as input data. In both studies, neutral standing posture was considered with
      weights up to 380 N held in hands with arms extended close to the body either in
      front or on sides. RESULTS: Predicted muscle forces were in satisfactory
      agreement with measured EMG activities. The activity in extensor muscles
      significantly increased with the load magnitude when held in front, a trend that
      disappeared as loads were held on sides. Abdominal muscles remained relatively
      silent. Large compression forces of approximately 2000 N were computed in lower
      lumbar levels when 380 N was held in front. Coactivity in abdominal muscles
      markedly increased internal loads and stability margin. CONCLUSION: A tradeoff
      exists between lower loads in passive tissues (i.e., tissue risk of failure) and
      higher stability margins as both increase with greater muscle coactivation.
      Greater muscle activity observed under load held in front did not necessarily
      yield larger stability margin as the position of load appeared to play an
      important role as well. The strength of the proposed model is in realistic
      consideration of both passive-active structures under postures and
      gravity/external loads, yielding results that satisfy kinematics, equilibrium,
      and stability requirements in all directions along the spine.

PMID- 15564913
TI  - Static load repetition is a risk factor in the development of lumbar cumulative
      musculoskeletal disorder.
AB  - STUDY DESIGN: In vivo feline model subjected to variable number of repetitions of
      a short static lumbar flexion followed by an equally long rest period.
      OBJECTIVES: The purpose of this study was to determine the influence of the
      number of repetitions as a risk factor in promoting a cumulative low back
      disorder in the feline model. SUMMARY OF BACKGROUND DATA: Epidemiologic data
      point out that the increased number of repetitions of static lumbar loading is a
      major risk factor in the development of cumulative low back disorder.
      Biomechanical and physiologic confirmation of the epidemiology is lacking. Recent
      work demonstrated that repetitive static loading results in accumulation of creep
      in the lumbar viscoelastic tissues, resulting in a neuromuscular disorder
      consisting of spasms during loading and hyperexcitability of lumbar muscles
      during following rest. It was also shown that the load magnitude is a major risk
      factor. It is hypothesized that increased number of repetitions of static load
      periods result in increased severity of the resulting neuromuscular disorder.
      METHODS: Static lumbar flexion of 10 minutes duration followed by 10 minutes rest
      was repeated three times in one experimental group, six times in the second, and
      nine times in the third group. In all groups, the creep developing in the lumbar
      viscoelastic tissues as well as the reflexive EMG from the multifidus were
      monitored during the flexion/rest periods and throughout a 7-hour recovery period
      after the repetitions. RESULTS: Creep developed and accumulated during each of
      the flexion/rest periods in the three experimental protocols, with larger
      residual creep at the end of the nine repetitions. A residual creep was still
      present at the end of the 7 hours of recovery allowed in each of the three
      groups. During the flexion/rest sessions, EMG spasms were present, and the
      presence of an initial hyperexcitability was detected during the 7 hours of
      recovery in all the preparations. The presence of a delayed hyperexcitability was
      revealed only in the group subjected to nine flexion/rest periods, while it was
      not observed in the groups subjected to three and six flexion/rest repetitions.
      The statistical analysis (post hoc Fisher test) performed on the normalized
      integrated EMG and displacement data during the recovery phase showed a
      significant difference between the nine repetitions group and the other two
      groups (P < 0.0001). The two-way ANOVA analysis revealed a significant effect of
      time (P < 0.005) and number of repetitions (P < 0.0001) on all considered
      parameters. CONCLUSIONS: It was concluded that a cumulative neuromuscular
      disorder develops because of repetition of static lumbar flexion, and the
      severity of the disorder provoked is magnified by the number of repetitions.
      Despite the highly favorable 1:1 work-to-rest ratio and the 7-hour post loading
      rest period, a full recovery of creep was not obtained in this study.

PMID- 15564914
TI  - ISSLS prize winner: A study of diffusion in human lumbar discs: a serial magnetic
      resonance imaging study documenting the influence of the endplate on diffusion in
      normal and degenerate discs.
AB  - STUDY DESIGN: An in vivo serial magnetic resonance imaging study of diffusion
      characteristics in human lumbar discs over 24 hours in healthy volunteers and
      patients with low back pain. OBJECTIVES: To document the temporal pattern of
      diffusion in normal human lumbar discs and to study the influence of the
      vascularity of bone and the status of endplate on diffusion in the normal and
      degenerate discs. SUMMARY OF BACKGROUND DATA: Diffusion is the only source of
      nutrition to the discs, but no firm data are available on pattern of diffusion in
      humans. More data on this important subject are required to improve our
      understanding of disc degeneration and to probe research possibilities for
      preventing the same. METHODS: The diffusion pattern over 24 hours following
      gadodiamide injection was studied in 150 discs (96 normal and 54 degenerate).
      Signal intensity values for three regions of interest in bone (i.e., vertebral
      body, subchondral bone, and endplate zone) and seven in the disc were calculated,
      and normal percentiles of diffusion were derived for these regions. Enhancement
      percentage for each time period, peak enhancement percentage for each region, and
      the time taken to achieve peak enhancement percentage (Tmax) were used to define
      and compare diffusion characteristics and plot a time-intensity curve to document
      the 24-hour temporal pattern. The correlation of blood flow of the bone as
      measured by peak enhancement percentage of vertebral body, the status of the
      endplate zone as measured by the peak enhancement percentage, and Tmax of the
      endplate zone were correlated with the diffusion of the disc.Univariate analysis
      of variance, multiple comparisons, appropriate tests for significance, and
      stepwise linear regression analysis were used for analysis of the data using SPSS
      software. RESULTS: In normal discs, a "diffusion march" from the vertebral body
      to the center of disc was noted with the SImax being observed at 5 min in the
      vertebral body and subchondral bone, at 2 hours in the endplate zone, and at 6
      hours in the nucleus pulposus. A significant difference in mean peak enhancement
      percentage was observed between that of the body and the discs in those less than
      10 years and those above the age of 20 years (P < 0.001). Alterations in endplate
      zone produced distinct magnetic resonance imaging signs of disturbance in
      diffusion, which offered a reliable noninvasive method of identifying endplate
      cartilage damage. Stepwise linear regression analysis showed that the significant
      variable influencing diffusion to the center of the nucleus pulposus of the total
      sample was peak enhancement percentage of endplate zone (R2 = 0.216; P < 0.001),
      that of degenerate discs was peak enhancement percentage of endplate zone (R2 =
      0.322; P < 0.001), and that of normal discs (R2 = 0.324; P < 0.001) was age.
      CONCLUSIONS: Serial postcontrast magnetic resonance imaging studies offer a
      reliable method of assessing the diffusion of the discs and the functional status
      of the endplate cartilage. Endplate cartilage damage increases with age and
      produces considerable changes in diffusion. The present study has described
      reliable signs by which these damages can be identified in vivo. Aging and
      degeneration have been shown to be two separate processes by documenting clear
      cut differences in diffusion. The present data encourage use of diffusion studies
      as a noninvasive method to assess the physiologic status of the disc and endplate
      and to study the effect of drugs, smoking, mechanical loading, exercises, etc. on
      the physiology of the disc.

PMID- 15564915
TI  - The occurrence of anular tears and their relation to lifetime back pain history:
      a cadaveric study using barium sulfate discography.
AB  - STUDY DESIGN: The occurrence of anular tears and general disc degeneration of the
      lumbar spine was studied in relation to the lifetime frequency of back pain.
      SUMMARY OF BACKGROUND DATA: Although anular tears and ruptures are common targets
      for diagnostic and therapeutic approaches, the relationship between disc findings
      and back pain has been weak or nonexistent. METHODS: The data comprised barium
      sulfate discograms of lumbar spine levels from 157 male cadavers. The extent of
      "anular tears" and "general disc degeneration" based on posterior-anterior and
      side views were evaluated separately using a 4-point scale. Lifetime history of
      back pain occurrence and work were obtained from the families of 86 cadavers. To
      assess whether the risk of back pain changed with the severity of findings or the
      level of disc, we applied trend tests and proportional-odds logistic models for
      occurrence data. RESULTS: In early adulthood, the risk of anular tears was 0.6 to
      0.7, whereas at retirement age, tears were practically unavoidable. The risk of
      full anular tears with barium sulfate leaking ("leaking" tear) was estimated to
      be 0.10 and 0.35 among the men in the age groups of 20 to 49 and 50 to 59 years,
      respectively. The risk of "leaking" tears was greatest at the L5-S1 levels. There
      were less severe degenerative findings associated with sedentary occupation but
      no differences between driving and physically light and heavy occupations.
      Overall, the risk of any anular tears and any general degeneration as defined was
      similar. The frequency of back pain had a highly significant relation to the
      occurrence of tears (model-based P = 0.0009). With a "leaking" tear, the model
      based estimate of the risk of frequent lifetime back pain was 0.42, with an
      "outer" tear the risk was 0.20, and with no tears or "inner" tears the risk was
      0.10 (the observed prevalence was 0). The effect of occupational loading was of
      borderline significance (P = 0.045). CONCLUSION: Anular degeneration of the
      lumbar discs appear earlier and are more clearly related to back pain than
      previously thought, most probably due to the better sensitivity of the BaSO4
      discography method to detect tears.

PMID- 15564916
TI  - Introduction: disc degeneration: summary.

PMID- 15564917
TI  - Lumbar disc degeneration: epidemiology and genetic influences.
AB  - STUDY DESIGN: A literature review. OBJECTIVE: To synthesize the scientific
      literature on the prevalence of lumbar disc degeneration and factors associated
      with its occurrence, including genetic influences. METHODS: A literature review
      was conducted of the prevalence of disc degeneration. Studies of the etiology of
      disc degeneration were summarized, with particular attention given to studies of
      genetic influences. RESULTS AND CONCLUSIONS: There are extreme variations in the
      reported prevalence of specific degenerative findings of the lumbar spine among
      studies, which cannot be explained entirely by age or other identifiable risk
      factors (e.g., prevalence figures for disc narrowing varied from 3% to 56%). It
      is likely that these variations are due, in great part, to inconsistencies in
      case definitions and measurements, which are impeding epidemiologic research on
      disc degeneration. Research conducted over the past decade has led to a dramatic
      shift in the understanding of disc degeneration and its etiology. Previously,
      heavy physical loading was the main suspected risk factor for disc degeneration.
      However, results of exposure-discordant monozygotic and classic twin studies
      suggest that physical loading specific to occupation and sport has a relatively
      minor role in disc degeneration, beyond that of upright postures and routine
      activities of daily living. Recent research indicates that heredity has a
      dominant role in disc degeneration, explaining 74% of the variance in adult
      populations studied to date. Since 1998, genetic influences have been confirmed
      by the identification of several gene forms associated with disc degeneration.

PMID- 15564918
TI  - Biology of intervertebral disc aging and degeneration: involvement of the
      extracellular matrix.
AB  - STUDY DESIGN: A review of current knowledge and opinions concerning the biologic
      changes that take place during development, maturation and degeneration of the
      intervertebral disc. OBJECTIVE: To provide an overview of the changes that occur
      in structure and composition of the extracellular matrix of the intervertebral
      disc and to explain the origin of such changes and their functional consequences.
      SUMMARY OF BACKGROUND DATA: The structure of the intervertebral disc, and, in
      particular, the composition of its extracellular matrix, changes throughout life,
      ultimately resulting in tissue degeneration in the adult. METHODS: A review of
      the published scientific literature. RESULTS: In the young disc, the outer anulus
      fibrosus and inner nucleus pulposus have clear physical and molecular properties,
      although these differences become less distinct in the adult. The age changes are
      due to variations in both the abundance and structure of the macromolecules,
      particularly aggrecan, and the structural variations may be due to changes in
      both synthesis and degradation. It is not clear how many of the changes are by
      design to adapt to the altered environment of the growing spine. However, it is
      commonly thought that the degradative changes are detrimental to disc function, a
      property that is exacerbated by the inability of the mature avascular disc to
      remove and replace accumulated degradation products. The rate at which these
      detrimental changes occur may vary between individuals because of genetic,
      biomechanical, and nutritional differences. Such changes are thought to form the
      basis of tissue loss associated with disc degeneration. CONCLUSION: Changes in
      intervertebral disc structure throughout life ultimately result in tissue
      degeneration and the need for medical intervention. Current research is aimed at
      trying to restore the integrity of the degenerate disc matrix by biologic means,
      although at present it is not clear what the structure of the most appropriate
      repair tissue should be or how it can be achieved.

PMID- 15564919
TI  - Nutrition of the intervertebral disc.
AB  - STUDY DESIGN: A review of the literature on disc nutrition. OBJECTIVES: To
      summarize the information on disc nutrition in relation to disc degeneration.
      SUMMARY OF THE BACKGROUND DATA: The disc is avascular, and the disc cells depend
      on diffusion from blood vessels at the disc's margins to supply the nutrients
      essential for cellular activity and viability and to remove metabolic wastes such
      as lactic acid. The nutrient supply can fail due to changes in blood supply,
      sclerosis of the subchondral bone or endplate calcification, all of which can
      block transport from blood supply to the disc or due to changes in cellular
      demand. METHODS: A review of the studies on disc blood supply, solute transport,
      studies of solute transport in animal and human disc in vitro, and of theoretical
      modeling studies that have examined factors affecting disc nutrition. RESULTS:
      Small nutrients such as oxygen and glucose are supplied to the disc's cells
      virtually entirely by diffusion; convective transport, arising from load-induced
      fluid movement in and out of the disc, has virtually no direct influence on
      transport of these nutrients. Consequently, there are steep concentration
      gradients of oxygen, glucose, and lactic acid across the disc; oxygen and glucose
      concentrations are lowest in the center of the nucleus where lactic acid
      concentrations are greatest. The actual levels of concentration depend on the
      balance between diffusive transport and cellular demand and can fall to critical
      levels if the endplate calcifies or nutritional demand increases. CONCLUSIONS:
      Loss of nutrient supply can lead to cell death, loss of matrix production, and
      increase in matrix degradation and hence to disc degeneration.

PMID- 15564920
TI  - Cell mechanics and mechanobiology in the intervertebral disc.
AB  - STUDY DESIGN: A review is presented on current knowledge of the micromechanical
      factors in the intervertebral disc, their role in modifying cell biology, and
      changes with degeneration. OBJECTIVES: To identify current knowledge, knowledge
      gaps, and areas for future research in micromechanics of the intervertebral disc.
      SUMMARY OF BACKGROUND DATA: Mechanical factors play important roles in the
      initiation and progression of intervertebral disc degeneration. Evidence suggests
      that substantial biologic remodeling occurs in the intervertebral disc in
      response to mechanical stimuli that may play a critical role in determining the
      fate of a degenerating intervertebral disc. Information is needed on the precise
      mechanical stimuli that these cells experience and the mechanisms that govern
      their responses. METHODS: A review is presented of cell morphology, cell
      mechanics, and the internal strains and other mechanical factors predicted to
      occur at the cell level. A review of intervertebral disc cell responses to well
      controlled physical stimuli is also presented with a focus on in vitro studies of
      explants and isolated cells. RESULTS: Important differences in cell morphology,
      mechanics, micromechanical factors, and mechanobiology are noted to occur between
      cells of the nucleus pulposus and anulus fibrosus. Changes in these features with
      degeneration are critically understudied, particularly degeneration-associated
      changes in cell morphology, cell mechanics, and altered physiology with
      mechanical loading. CONCLUSIONS: Information on the mechanisms that govern cell
      responses to mechanical stimuli in the intervertebral disc are just emerging.
      Studies must address determination of the factors that control micromechanical
      stimuli, but also mechanisms by which mechanics may interact with genetic factors
      to regulate expression and remodeling of extracellular matrix molecules,
      cytokines and mediators of pain and inflammation in degenerating tissue.

PMID- 15564921
TI  - Mechanical conditions that accelerate intervertebral disc degeneration: overload
      versus immobilization.
AB  - STUDY DESIGN: A review of the literature on macromechanical factors that
      accelerate disc degeneration with particular focus on distinguishing the roles of
      immobilization and overloading. OBJECTIVE: This review examines evidence from the
      literature in the areas of biomechanics, epidemiology, animal models, and
      intervertebral disc physiology. The purpose is to examine: 1) what are the
      degeneration-related alterations in structural, material, and failure properties
      in the disc; and 2) evidence in the literature for causal relationships between
      mechanical loading and alterations in those structural and material properties
      that constitute disc degeneration. SUMMARY OF BACKGROUND DATA: It is widely
      assumed that the mechanical environment of the intervertebral disc at least in
      part determines its rate of degeneration. However, there are two plausible and
      contrasting theories as to the mechanical conditions that promote degeneration:
      1) mechanical overload; and 2) reduced motion and loading. RESULTS: There are a
      greater number of studies addressing the "wear and tear" theory than the
      immobilization theory. Evidence is accumulating to support the notion that there
      is a "safe window" of tissue mechanical conditions in which the discs remain
      healthy. CONCLUSIONS: It is concluded that probably any abnormal loading
      conditions (including overload and immobilization) can produce tissue trauma
      and/or adaptive changes that may result in disc degeneration. Adverse mechanical
      conditions can be due to external forces, or may result from impaired
      neuromuscular control of the paraspinal and abdominal muscles. Future studies
      will need to evaluate additional unquantified interactions between biomechanics
      and factors such as genetics and behavioral responses to pain and disability.

PMID- 15564922
TI  - Recent advances in analytical modeling of lumbar disc degeneration.
AB  - STUDY DESIGN: Review of the most recent advances in the development of poro
      elastic analytical models that include physiologic parameters used for
      understanding lumbar disc degeneration due to repetitive loading. OBJECTIVES: To
      discuss how poro-elastic finite element models that include physiologic
      parameters such as strain-dependent permeability and porosity and regional
      variation of poro-elastic material properties of a motion segment can be used to
      understand the effect of disc degeneration due to cyclic loading on the disc
      biomechanical properties. SUMMARY OF BACKGROUND DATA: Mechanical response of the
      spine to various dynamic loading conditions can be analyzed using in vitro and in
      vivo studies. Ethical concerns, interpretation of conclusions reached using
      animal studies, and lack of detailed stress distributions in the disc components
      are the major disadvantages in using in vivo studies for understanding disc
      degeneration process. Intraspecimen variability, noninclusion of muscle activity,
      and difficulty of influx of fluid into the disc during unloading are some of the
      disadvantages while using in vitro models to understand disc degeneration. The
      poro-elastic finite element models can provide a method that can circumvent the
      disadvantages mentioned above and allow a way to understand the relationship
      between biomechanical performance of the disc due to cyclic loading and disc
      degeneration. METHODS: Several types of finite element model were developed in
      understanding relationship between disc degeneration and associated changes in
      biomechanical properties. Simplest among them include material and geometric
      nonlinearity of the disc and was used to predict failure in the disc anulus and
      endplates under static loading conditions. Response of the lumbar disc under
      creep loading was studied using poro-elastic models. These models were further
      refined by including swelling pressure and variable permeability due to change in
      porosity under load to understand time-dependent deformation of a lumbar disc in
      a multiple creep compression expansion loading. Regional variation of strain
      dependent permeability and osmotic pressure was included to further refine the
      poro-elastic finite element model. This refined model was used to study the
      effect of disc degeneration on biomechanical properties when cyclic loading was
      applied to the lumbar disc. RESULTS: The refined model that included regional
      variation of strain-dependent permeability and osmotic pressure was validated by
      comparing diurnal change in total stature measured in vivo. The study showed that
      disc height loss was larger after considerable number of cyclic loadings both in
      normal and degenerated discs. Cyclic loading also showed that Grade I discs were
      much more flexible than Grade IV discs. The disc stiffness also decreased as the
      load cycle increased. CONCLUSIONS: A number of different approaches have been
      used to address the issue of disc degeneration. Poro-elastic finite element model
      including strain-dependent permeability and osmotic pressure is the most popular
      analytical tool currently available that can be used to understand how cyclic
      loading affects the biomechanical characteristics of a degenerated lumbar disc.
      However, it is important to note that a complete understanding of the behavior of
      the intervertebral disc will ultimately be arrived using a combination of
      analytical models, such as the models presented here, in addition to in vitro and
      in vivo experimental methods.

PMID- 15564923
TI  - Animal models of intervertebral disc degeneration: lessons learned.
AB  - STUDY DESIGN: A literature review of intervertebral disc degeneration animal
      models. OBJECTIVES: Focus is placed on those models that suggest degeneration
      mechanisms relevant to human. SUMMARY OF BACKGROUND DATA: Medical knowledge from
      observational epidemiology and intervention studies suggest many etiologic causal
      factors in humans. Animal models can provide basic science data that support
      biologic plausibility as well as temporality, specificity, and dose-response
      relationships. METHODS: Studies are classified as either experimentally induced
      or spontaneous, where experimentally induced models are subdivided as mechanical
      (alteration of the magnitude or distribution of forces on the normal joint) or
      structural (injury or chemical alteration). Spontaneous models include those
      animals that naturally develop degenerative disc disease. RESULTS:
      Mechanobiologic relationships are apparent as stress redistribution secondary to
      nuclear depressurization (by injury or chemical means) can cause cellular
      metaplasia, tissue remodeling, and pro-inflammatory factor production. Moderate
      perturbations can be compensated for by cell proliferation and matrix synthesis,
      whereas severe perturbations cause architectural changes consistent with human
      disc degeneration. CONCLUSIONS: These models suggest that two stages of
      architectural remodeling exist in humans: early adaptation to gravity loading,
      followed by healing meant to reestablish biomechanical stability that is slowed
      by tissue avascularity. Current animal models are limited by an incomplete set of
      initiators and outcomes that are only indirectly related to important clinical
      factors (pain and disability).

PMID- 15564924
TI  - Medical imaging of intervertebral disc degeneration: current status of imaging.
AB  - STUDY DESIGN: The author reviewed literature and reports on spine imaging,
      selected key articles in which novel imaging strategies were described, and
      prepared a review of currently developing imaging strategies in intervertebral
      disc degeneration. OBJECTIVES: To provide a review of imaging in intervertebral
      disc degeneration that covers the current methodology briefly and describes
      developing techniques in detail. SUMMARY OF BACKGROUND DATA: Computed tomography
      and magnetic resonance imaging provide excellent anatomic images of the spine.
      However, anatomic imaging of the spine does not reliably identify the source of
      pain in patients with intervertebral disc degeneration. Many functional imaging
      techniques are suited to the study of the spine. Some of these techniques will
      improve our understanding of intervertebral disc degeneration and clinical
      symptomatology. METHODS: The author selected reports in the current literature
      for further review and attempted to describe succinctly the material in the
      reports that are most relevant to spine imaging. RESULTS: New and potentially
      useful imaging strategies for spine imaging include dynamic computed tomography,
      dynamic magnetic resonance imaging, functional magnetic resonance imaging,
      diffusion imaging, and magnetic resonance spectroscopy. CONCLUSIONS:
      Technological advances in magnetic resonance imaging and computed tomography
      imaging continue to offer more opportunities to investigate and diagnose back
      pain and intervertebral disc degeneration.

PMID- 15564925
TI  - Growth factors and treatment of intervertebral disc degeneration.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To review the most recent findings of
      the effects of growth factors on the intervertebral disc and, further, to discuss
      trends in the biologic repair of the degenerated intervertebral disc. SUMMARY OF
      BACKGROUND DATA: Since early in 1990, advancements in molecular biology and cell
      culture technology have enabled researchers to accumulate knowledge about the in
      vitro actions of growth factors on intervertebral disc cells. More recently, the
      use of growth factors for the biologic regeneration of the intervertebral disc is
      of increasing interest to the orthopedic field, and indeed, some preliminary in
      vivo studies have proven their efficacy. METHODS: Based on a literature search
      conducted using available databases, such as the National Library of Medicine, as
      well as data presented at scientific conferences held in the past 2 years,
      primarily in the United States, the current status of biologic therapy for disc
      degeneration using growth factors was summarized. RESULTS: With increasing
      evidence to support the feasibility of biologically regenerating intervertebral
      disc tissues, the clinical application of growth factors has become more
      plausible. The effects of growth factors on the metabolism of intervertebral disc
      cells or tissues have been extensively studied using in vitro approaches. More
      recently, the efficacy of an injection of growth factor protein to reverse disc
      regeneration has been shown in vivo using a small animal disc degeneration model.
      The confirmation of those effects and a detailed dose-response study, as well as
      a long-term safety study, in a large animal model is highly anticipated.
      Hopefully, the expansion of the clinical use of improved imaging techniques for
      the early detection of disc degeneration and promising results about the effects
      of growth factors on intervertebral disc regeneration will benefit the human
      population in the near future. CONCLUSIONS: The results from these in vitro and
      in vivo studies reviewed here clearly suggest the potential usefulness of growth
      factor injections as a new approach to restore intervertebral disc degeneration
      at an early stage.

PMID- 15564926
TI  - Gene therapy approaches for intervertebral disc degeneration.
AB  - STUDY DESIGN: Review of the literature concerning the development of gene therapy
      approaches for the treatment of intervertebral disc degeneration. OBJECTIVES: To
      provide an overview of gene therapy principles, summarize the results of
      completed gene therapy studies, and discuss considerations for the direction of
      future research. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration is
      characterized by progressive loss of the proteoglycan matrix in the nucleus
      pulposus. Exogenous growth factors have been shown to transiently increase matrix
      synthesis. Gene therapy offers exciting potential to induce and sustain
      endogenous production of growth factors within the intervertebral disc and thus
      possibly alter the degenerative course. METHODS: Published and presented
      scientific literature was examined. RESULTS/CONCLUSIONS: Several in vitro and in
      vivo studies have documented the capacity of gene therapy to favorably modify the
      biologic functions of intervertebral disc cells with the delivery of the cDNA for
      various growth factors. Currently, investigators are exploring the efficacy and
      safety of gene therapy in animal models of degeneration. With promising initial
      results and an immense potential clinical impact, gene therapy approaches for
      treatment of intervertebral disc degeneration will continue to receive dedicated
      research efforts.

PMID- 15564927
TI  - Intervertebral disc arthroplasty.
AB  - STUDY DESIGN: Review article of current knowledge of disc arthroplasty.
      OBJECTIVES: To review the rationale for disc replacement, the general principles
      of design, and early clinical results. SUMMARY OF BACKGROUND DATA: Disc
      arthroplasty is an emerging treatment for patients with disc degeneration. Its
      theoretical advantages are to maintain motion, decrease the incidence of adjacent
      segment degeneration, avoid complications related to fusion, and allow early
      return to function. METHODS: Literature review of currently implanted prostheses
      or those undergoing investigation. RESULTS: At this time, the theoretical
      advantages are unproven clinically but have been confirmed in biomechanical and
      kinematic investigations. Multicenter studies of both cervical and lumbar
      prostheses have shown short-term results equivalent to fusion. Neurologic
      complications and failures have been rare. Prosthetic subsidence and long-term
      wear will most likely be potential failure mechanisms. Thus far, with the
      exception of nucleoplasty, these problems have not been observed. CONCLUSIONS:
      The early results are satisfactory, but the basic premise that motion
      preservation will diminish adjacent segment degeneration is yet unproven. Long
      term results are unavailable and failure modes are unknown. Before implantation,
      the surgeon and patient must understand the experimental nature of the devices.

PMID- 15564929
TI  - Troponin: important in severe trauma and a first step in the biological marker
      revolution.

PMID- 15564930
TI  - Picking safe combinations.

PMID- 15564931
TI  - Incidence and significance of cardiac troponin I release in severe trauma
      patients.
AB  - BACKGROUND: The incidence and significance of troponin I release and its
      mechanism are unknown in severe trauma patients. The characteristics of this
      release were prospectively studied in such patients and correlated with presence
      of shock, existence of myocardial contusion, and outcome. METHODS: During a 24
      month period, serial electrocardiogram recordings and troponin I measurements
      were performed in all trauma patients admitted at a surgical intensive care unit.
      The diagnosis of a significant myocardial contusion was made on
      electrocardiographic criteria. According to the time course of troponin I, three
      groups of patients were defined a priori: very transient (</= 12 h) and limited
      release (troponin I < 2 microg/l), transient (</= 36 h) and significant release
      (troponin I >/= 2 microg/l), and sustained (> 36 h) and significant release
      (troponin I > 2 microg/l). In the last group, coronary artery angiography was
      performed. RESULTS: The incidence of troponin I release was 12% (95% confidence
      interval [CI], 9.6-14.4%) in 728 patients. A significant myocardial contusion was
      found in 35 patients (5%; 95% CI, 3.4-6.6%) and may occur in the absence of chest
      trauma and without troponin I release. Sensitivity, specificity, and positive and
      negative predictive values of troponin I for the diagnosis of myocardial
      contusion were 63, 98, 40, and 98%, respectively. Troponin I release was observed
      in 54 early (> 48 h) survivors (7%; 95% CI, 5.6-9.6%) without preexisting
      coronary artery disease. A sustained and significant release of troponin I (17
      patients) was frequently associated with chest trauma (82%) and constantly with
      electrocardiographic abnormalities. A coronary artery injury was found in 7
      patients (2 major and 5 minor vascular injuries) (1% of the whole group; 95% CI,
      0.4-2.0%). Mortality was similar in early survivors with (15%; 95% CI, 7-27%) or
      without (12%; 95% CI, 9-14%) troponin I release. The odds ratio for late
      mortality was 1.32 (95% CI, 0.61-2.85) in patients with troponin I release.
      CONCLUSIONS: Serial electrocardiogram recordings and troponin I assessments may
      be proposed for initial screening in high-risk trauma patients to detect
      anatomical cardiac injuries through the time course of circulating protein.
      Troponin I release does not have a prognosis value in trauma patients.

PMID- 15564932
TI  - Estimation of the plasma effect site equilibration rate constant (ke0) of
      propofol in children using the time to peak effect: comparison with adults.
AB  - BACKGROUND: Targeting the effect site concentration may offer advantages over the
      traditional forms of administrating intravenous anesthetics. Because the lack of
      the plasma effect site equilibration rate constant (ke0) for propofol in children
      precludes the use of this technique in this population, the authors estimated the
      value of ke0 for propofol in children using the time to peak effect (tpeak)
      method and two pharmacokinetic models of propofol for children. METHODS: : The
      tpeak after a submaximal bolus dose of propofol was measured by means of the
      Alaris A-Line auditory evoked potential monitor (Danmeter A/S, Odense, Denmark)
      in 25 children (aged 3-11 yr) and 25 adults (aged 35-48 yr). Using tpeak and two
      previously validated sets of pharmacokinetic parameters for propofol in children,
      Kataria's and that used in the Paedfusor (Graseby Medical Ltd., Hertfordshire,
      United Kingdom), the ke0 was estimated according to a method recently published.
      RESULTS: The mean tpeak was 80 +/- 20 s in adults and 132 +/- 49 s in children (P
      < 0.001). The median ke0 in children was 0.41 min(-1) with the model of Kataria
      and 0.91 min(-1) with the Paedfusor model (P < 0.01). The corresponding t1/2 ke0
      values, in minutes, were 1.7 and 0.8, respectively (P < 0.01). CONCLUSIONS: :
      Children have a significantly longer tpeak of propofol than adults. The values of
      ke0 of propofol calculated for children depend on the pharmacokinetic model used
      and also can only be used with the appropriate set of pharmacokinetic parameters
      to target effect site in this population.

PMID- 15564933
TI  - Spectral entropy and bispectral index as measures of the electroencephalographic
      effects of sevoflurane.
AB  - BACKGROUND: Recently, entropy algorithms have been proposed as
      electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda
      (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic
      monitor designed for measuring depth of anesthesia. The monitor calculates a
      state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response
      entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors
      investigated the dose-response relation of SE and RE during sevoflurane
      anesthesia in comparison with the Bispectral Index (BIS). METHODS: Sixteen
      patients were studied without surgical stimulus. Anesthesia was induced by
      sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations
      were increased and subsequently decreased and increased two to four times until
      the measurement was stopped and patients were intubated for surgery. The
      performances of SE, RE, and BIS to predict the estimated sevoflurane effect site
      concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic
      modeling, were compared by calculating the correlation coefficients and the
      prediction probability. RESULTS: State entropy, RE, and BIS values decreased
      continuously over the observed concentration range of sevoflurane. Correlation
      coefficients were slightly but not significantly better for entropy parameters
      (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85
      +/- 0.12). Calculating the prediction probability confirmed these results with a
      prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE,
      respectively, and 0.80 +/- 0.06 for BIS. CONCLUSION: State entropy and RE seem to
      be useful electroencephalographic measures of sevoflurane drug effect.

PMID- 15564934
TI  - Comparative evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral
      Index monitor during propofol-remifentanil anesthesia.
AB  - BACKGROUND: Different analytical concepts were introduced to quantify the changes
      of the electroencephalogram. The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda
      Division, Instrumentarium Corp., Helsinki, Finland) was the first commercial
      monitor based on the entropy generating two indices, the state entropy (SE) and
      the response entropy (RE). The aim of the current study was to compare the
      accuracy of SE and RE with the Bispectral Index(R) monitor (BIS(R); Aspect
      Medical Systems, Newton, MA) during propofol-remifentanil anesthesia. METHODS:
      The authors investigated 20 female patients during minor gynecologic surgery. SE,
      RE, BIS, mean arterial blood pressure, heart rate, and sedation level were
      recorded every 20 s during stepwise increase (target-controlled infusion, 0.5
      microg/ml) of propofol until the patients lost response. Five minutes after loss
      of response, remifentanil infusion (0.4 microg . kg(-1) . min(-1)) was started.
      Spearman correlation coefficient and prediction probability were calculated for
      sedation levels with SE, RE, BIS, mean arterial blood pressure, and heart rate.
      The ability of the investigated parameters to distinguish between the anesthesia
      steps awake versus loss of response, awake versus anesthesia, anesthesia versus
      first reaction, and anesthesia versus extubation was analyzed with the prediction
      probability. RESULTS: SE correlates best with sedation levels, but no significant
      differences of the prediction probability values among SE, RE, and BIS were
      found. The prediction probability for all investigated steps of anesthesia did
      not show significant differences among SE, RE, and BIS. SE, RE, and BIS were
      superior to mean arterial blood pressure and heart rate. CONCLUSION: SE, RE, and
      BIS revealed similar information about the level of sedation and allowed the
      authors to distinguish between different steps of anesthesia. Both monitors
      provided useful additional information for the anesthesiologist.

PMID- 15564935
TI  - Platelet gene polymorphisms and cardiac risk assessment in vascular surgical
      patients.
AB  - BACKGROUND: Current perioperative cardiac risk assessment tools use historic and
      surgical factors to stratify patient risk. Polymorphisms in platelet glycoprotein
      (GP) IIIa and GPIbalpha are associated with myocardial ischemic risk in
      nonsurgical settings, but their relation to perioperative ischemia is unclear.
      The authors hypothesized that platelet genotype would be an independent predictor
      of postoperative myocardial ischemia and would improve risk assessment when added
      to clinical factors. METHODS: One hundred ninety-six patients who underwent
      infrainguinal, abdominal aortic, or thoracoabdominal vascular surgery were
      evaluated for clinical and genetic factors that might predict the development of
      postoperative myocardial ischemia. Genomic DNA was genotyped for the Leu33Pro
      polymorphism of GPIIIa and the Thr145Met polymorphism of GPIbalpha. Myocardial
      ischemic outcome was determined by review of the medical record for cardiac death
      or myocardial infarction and by surveillance troponin I and automated continuous
      12-lead electrocardiographic analysis. RESULTS: Sixty-five patients (33%)
      experienced one or more ischemic endpoints (2% death, 5% myocardial infarction,
      20% troponin+, 22% electrocardiogram+). The Pro33 (adjusted odds ratio [OR], 2.4
      [95% confidence interval, 1.2-6.2]) and Met145 (OR 3.4 [1.4-9.3]) genotypes were
      independent predictors of composite ischemic outcome by multivariate regression,
      as were diabetes mellitus (OR 4.0 [1.7-12.5]), abdominal aortic surgery (OR 4.1
      [1.7-14.4]), and thoracoabdominal aortic surgery (OR 6.4 [2.7-23.8]). The
      addition of platelet gene polymorphisms to clinical factors improved fit
      (likelihood ratio testing chi-square = 13.5, P < 0.001) of an ischemia prediction
      model. The derived risk assessment tool had a receiver operator characteristic
      curve of 0.73 (0.65-0.81) compared with 0.64 (0.57-0.74) for a model excluding
      genetic factors (P = 0.04). A significant relation between the GPIbalpha
      polymorphism and ischemic outcome remained after excluding electrocardiographic
      ischemia from the composite endpoint. CONCLUSIONS: Platelet polymorphisms are
      independent risk factors for postoperative myocardial ischemia and improve a risk
      prediction model when added to historic and surgical risk factors.

PMID- 15564936
TI  - Myocardial performance index with sevoflurane-pancuronium versus fentanyl
      midazolam-pancuronium in infants with a functional single ventricle.
AB  - BACKGROUND: Patients with congenital heart disease characterized by a functional
      single ventricle make up an increasing number of patients presenting for cardiac
      or noncardiac surgery. Conventional echocardiographic methods to measure left
      ventricular function, i.e., ejection fraction, are invalid in these patients
      because of altered ventricular geometry. Two recently described Doppler
      echocardiographic modalities, the myocardial performance index and Doppler tissue
      imaging, can be applied to single-ventricle patients because they are independent
      of ventricular geometry. This study assessed the changes in myocardial
      performance index and Doppler tissue imaging in response to two anesthetic
      regimens, fentanyl-midazolam-pancuronium and sevoflurane-pancuronium. METHODS:
      Thirty patients aged 4-12 months with a functional single ventricle were
      randomized to receive fentanyl-midazolam or sevoflurane. Myocardial performance
      index and Doppler tissue imaging were measured by transthoracic echocardiography
      at baseline and two clinically relevant dose levels. RESULTS: Sixteen patients
      receiving sevoflurane and 14 receiving fentanyl-midazolam were studied.
      Myocardial performance index was unchanged from baseline with either agent
      (fentanyl-midazolam: 0.50 +/- 15 baseline vs. 0.51 +/- 0.15 at dose 2;
      sevoflurane: 0.42 +/- 0.14 baseline vs. 0.46 +/- 0.09 at dose 2). Doppler tissue
      imaging S (systolic)- and E (early diastolic)-wave velocities in the lateral
      ventricular walls at the level of the atrioventricular valve annulus were
      unchanged in the sevoflurane group; however, both Doppler tissue imaging S- and E
      wave velocities were decreased significantly from baseline at dose 1 and dose 2
      with fentanyl-midazolam, consistent with decreased longitudinal systolic and
      diastolic ventricular function. CONCLUSIONS: Myocardial performance index, a
      global measurement of combined systolic and diastolic ventricular function, is
      not affected by commonly used doses of fentanyl-midazolam or sevoflurane in
      infants with a functional single ventricle.

PMID- 15564937
TI  - Proper shoulder position for subclavian venipuncture: a prospective randomized
      clinical trial and anatomical perspectives using multislice computed tomography.
AB  - BACKGROUND: Although the Trendelenburg position and shoulder bracing are
      recommended for safe subclavian venipuncture, the optimal shoulder position
      remains unclear. The current study observed spatial relations between the
      subclavian vein and surrounding structures using multislice computed tomography
      to determine optimal shoulder position for safe subclavian venipuncture and then
      conducted a small follow-up clinical trial to confirm these findings. METHODS:
      Thoracic multislice computed tomography was performed for seven adult volunteers
      at three shoulder positions: elevated (up); neutral; and lowered caudally (down).
      Overlap and distance between the clavicle and the subclavian vein and the
      diameter of the subclavian vein were measured. Anatomical relations between the
      subclavian artery and vein were also observed. The success rate for subclavian
      venipuncture was then compared between the up and down shoulder positions in 30
      patients. RESULTS: In the multislice computed tomography study, the mean overlap
      ratios between clavicle and subclavian vein in the up, neutral, and down
      positions were 33.5, 36.9, and 40.0%, respectively. Overlap increased with lower
      shoulder position (up < neutral < down; P < 0.05). The mean distances between the
      clavicle and the subclavian vein in the up, neutral, and down positions were 6.8,
      5.0, and 3.6 mm, respectively. Again, distance decreased with lower shoulder
      position (up < neutral < down; P < 0.05). The diameter of the subclavian vein did
      not differ among the three shoulder positions. The success rate for subclavian
      venipuncture was significantly higher in the down position compared with the up
      position (P = 0.003). CONCLUSIONS: Lowered shoulder position increases both
      overlap and proximity between the clavicle and the subclavian vein, producing a
      more constant relation between the clavicle and the subclavian vein, without
      affecting vein diameter. Proper use of a lowered shoulder position should thus
      increase the safety and reliability of subclavian venipuncture compared with
      other shoulder positions.

PMID- 15564938
TI  - Differential protective effects of volatile anesthetics against renal ischemia
      reperfusion injury in vivo.
AB  - BACKGROUND: Volatile anesthetics protect against cardiac ischemia-reperfusion
      injury via adenosine triphosphate-dependent potassium channel activation. The
      authors questioned whether volatile anesthetics can also protect against renal
      ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate
      dependent potassium channels, antiinflammatory effects of volatile anesthetics,
      or both are involved. METHODS: Rats were anesthetized with equipotent doses of
      volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or
      injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of
      renal ischemia and 3 h of reperfusion during anesthesia. RESULTS: Rats treated
      with volatile anesthetics had lower plasma creatinine and reduced renal necrosis
      24-72 h after injury compared with rats anesthetized with pentobarbital or
      ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane
      treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5
      mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats
      treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2
      mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least
      reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal
      cortices from volatile anesthetic-treated rats demonstrated reduced expression of
      intercellular adhesion molecule 1 protein and messenger RNA as well as messenger
      RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic
      treatment reduced renal cortex myeloperoxidase activity and reduced nuclear
      translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate
      dependent potassium channels are not involved in sevoflurane-mediated renal
      protection because glibenclamide did not block renal protection (creatinine: 2.4
      +/- 0.4 mg/dl, n = 3). CONCLUSION: Some volatile anesthetics confer profound
      protection against renal ischemia-reperfusion injury compared with pentobarbital
      or ketamine anesthesia by attenuating inflammation. These findings may have
      significant clinical implications for anesthesiologists regarding the choice of
      volatile anesthetic agents in patients subjected to perioperative renal ischemia.

PMID- 15564939
TI  - The inhibitory effects of isoflurane on protein tyrosine phosphorylation
      modulated contraction of rat aortic smooth muscle.
AB  - BACKGROUND: Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an
      important role in initiating and modulating vascular smooth muscle contraction.
      The aim of the current study was to examine the effects of isoflurane on sodium
      orthovanadate (Na3VO4), a potent protein tyrosine phosphatase inhibitor-induced,
      tyrosine phosphorylation-mediated contraction of rat aortic smooth muscle.
      METHODS: The Na3VO4-induced contraction of rat aortic smooth muscle and tyrosine
      phosphorylation of proteins including phospholipase Cgamma-1 (PLCgamma-1) and
      p44/p42 mitogen-activated protein kinase (MAPK) were assessed in the presence of
      different concentrations of isoflurane, using isometric force measurement and
      Western blotting methods, respectively. RESULTS: Na3VO4 (10(-4) m) induced a
      gradually sustained contraction and significant increase in protein tyrosine
      phosphorylation of a set of substrates including PLCgamma-1 and p42MAPK, all of
      which were markedly inhibited by genistein (5 x 10(-5) m), a tyrosine kinase
      inhibitor. Isoflurane (1.2-3.5%) dose-dependently depressed the Na3VO4-induced
      contraction (P < 0.05-0.005; n = 8). Isoflurane also attenuated the total density
      of the Na3VO4-induced, tyrosine-phosphorylated substrate bands and the density of
      tyrosine-phosphorylated PLCgamma-1 band and p42MAPK band (P < 0.05-0.005; n = 4)
      in a concentration-dependent manner. CONCLUSION: The findings of the current
      study, that isoflurane dose-dependently inhibits both the Na3VO4-stimulated
      contraction and tyrosine phosphorylation of a set of proteins including PLCgamma
      1 and p42MAPK in rat aortic smooth muscle, suggest that isoflurane depresses
      protein tyrosine phosphorylation-modulated contraction of vascular smooth muscle,
      especially that mediated by the tyrosine-phosphorylated PLCgamma-1 and MAPK
      signaling pathways.

PMID- 15564940
TI  - Maternal insufflation during the second trimester equivalent produces
      hypercapnia, acidosis, and prolonged hypoxia in fetal sheep.
AB  - BACKGROUND: Anecdotal reports suggest that the second trimester is the safest
      time to conduct a laparoscopic procedure on a pregnant patient, but this
      supposition has not been tested empirically. METHODS: Previously instrumented
      preterm sheep (total n = 8) at gestational day 90 (term, 145 days) were
      anesthetized and then insufflated with carbon dioxide for 60 min at a pressure of
      15 mmHg. Cardiovascular parameters were continuously recorded while blood gas
      status was determined before and at 15-min intervals during and up to 2 h after
      insufflation. RESULTS: Insufflation produced minimal maternal blood gas or
      cardiovascular changes except for a significant reduction in uterine blood flow.
      The decrease in perfusion increased fetal arterial blood partial pressure of
      carbon dioxide and decreased fetal pH, oxygen saturation, and oxygen content;
      there was also progressive fetal hypotension and bradycardia. After manually
      deflating the ewe, uterine blood flow returned to normal, and the fetal partial
      pressure of carbon dioxide and pH changes resolved within 1 h. However, fetal
      oxygen saturation and content remained depressed, and fetal cardiovascular status
      continued to decline during the 2-h postinsufflation monitoring period.
      CONCLUSION: Previous studies with near-term sheep determined that carbon dioxide
      pneumoperitoneum produces respiratory acidosis but does not decrease fetal
      oxygenation. In contrast, the current findings indicate that in the preterm
      fetus, insufflation-induced hypercapnia and acidosis are accompanied by prolonged
      fetal hypoxia and cardiovascular depression. This result suggests that additional
      work should be conducted to confirm the presumed safety of conducting minimally
      invasive procedures during the second trimester.

PMID- 15564941
TI  - Mg2+ dependence of halothane-induced Ca2+ release from the sarcoplasmic reticulum
      in skeletal muscle from humans susceptible to malignant hyperthermia.
AB  - BACKGROUND: Recent work suggests that impaired Mg(2+) regulation of the ryanodine
      receptor is a common feature of both pig and human malignant hyperthermia.
      Therefore, the influence of [Mg(2+)] on halothane-induced Ca(2+) release from the
      sarcoplasmic reticulum was studied in malignant hyperthermia-susceptible (MHS) or
      -nonsusceptible (MHN) muscle. METHODS: Vastus medialis fibers were mechanically
      skinned and perfused with solutions containing physiologic (1 mm) or reduced
      concentrations of free [Mg(2+)]. Sarcoplasmic reticulum Ca(2+) release was
      detected using fura-2 or fluo-3. RESULTS: In MHN fibers, 1 mm halothane
      consistently did not induce sarcoplasmic reticulum Ca(2+) release in the presence
      of 1 mm Mg(2+). It was necessary to increase the halothane concentration to 20 mm
      or greater before Ca release occurred. However, when [Mg(2+)] was reduced below 1
      mm, halothane became an increasingly effective stimulus for Ca(2+) release; e.g.,
      at 0.4 mm Mg(2+), 58% of MHN fibers responded to halothane. In MHS fibers, 1 mm
      halothane induced Ca(2+) release in 57% of MHS fibers at 1 mm Mg(2+). Reducing
      [Mg(2+)] increased the proportion of MHS fibers that responded to 1 mm halothane.
      Further experiments revealed differences in the characteristics of halothane
      induced Ca(2+) release in MHS and MHN fibers: In MHN fibers, at 1 mm Mg(2+),
      halothane induced a diffuse increase in [Ca(2+)], which began at the periphery of
      the fiber and spread slowly inward. In MHS fibers, halothane induced a localized
      C(2+)a release, which then propagated along the fiber. However, propagated Ca(2+)
      release was observed in MHN fibers when halothane was applied at an Mg(2+)
      concentration of 0.4 mm or less. CONCLUSIONS: When Mg(2+) inhibition of the
      ryanodine receptor is reduced, the halothane sensitivity of MHN fibers and the
      characteristics of the Ca release process approach that of the MHS phenotype. In
      MHS fibers, reduced Mg(2+) inhibition of the ryanodine receptor would be expected
      to have a major influence on halothane sensitivity. The Mg dependence of the
      halothane response in MHN and MHS may have important clinical implications in
      circumstances where intracellular [Mg(2+)] deviates from normal physiologic
      concentrations.

PMID- 15564942
TI  - Interaction of ropivacaine with cloned cardiac Kv4.3/KChIP2.2 complexes.
AB  - BACKGROUND: Inhibition of cardiac K channels by local anesthetic may contribute
      to QTc interval prolongation of the electrocardiogram and induction of
      ventricular arrhythmia. The transient outward current Ito has been identified as
      a toxicologically relevant target of bupivacaine. S(-)-ropivacaine has been
      developed as a safer alternative to bupivacaine. The effects of S(-)-ropivacaine
      on Ito have not been investigated. In human ventricular myocardium, Ito is formed
      by Kv4.3 and KChIP2.2 subunits. Therefore, the aim of this study was to establish
      the effects of S(-)-ropivacaine on human Kv4.3/KChIP2.2 channels. METHODS:
      Kv4.3/KChIP2.2 complementary DNA cloned from human heart was transiently
      transfected in Chinese hamster ovary cells. The pharmacologic effects of S(-)
      ropivacaine were investigated with the patch clamp method. RESULTS: Ropivacaine
      inhibited Kv4.3/KChIP2.2 channels in a concentration-dependent, stereospecific,
      and reversible manner. The IC50 value of S(-)-ropivacaine for inhibition of the
      charge conducted by Kv4.3/KChIP2.2 channel was 117 +/- 21 microm (n = 30). The
      local anesthetic accelerated macroscopic current decline with an IC50 value of 77
      +/- 11 microm (n = 30). It shifted the midpoint of channel activation into the
      depolarizing direction, and it slowed recovery from inactivation without altering
      steady state inactivation. Kv4.3 channels are more sensitive to the inhibitory
      effect than Kv4.3/KChIP2.2 channels. CONCLUSIONS: : The results are consistent
      with the idea that ropivacaine, by blocking Kv4.3/KChIP2.2 from the open state,
      interferes with the gating modifying effects of KChIP2.2 on Kv4.3 channels.
      Inhibition of Kv4.3/KChIP2.2 channels by the local anesthetic may contribute to
      the deterioration of cardiac function during events of intoxication.

PMID- 15564943
TI  - Isoflurane and desflurane impair right ventricular-pulmonary arterial coupling in
      dogs.
AB  - BACKGROUND: Halogenated anesthetics depress left ventricular function, but their
      effects on the right ventricle have been less well studied. Therefore, the
      authors studied the effects of isoflurane and desflurane on pulmonary arterial
      (PA) and right ventricular (RV) properties at baseline and in hypoxia. METHODS:
      Right ventricular and PA pressures were measured by micromanometer catheters, and
      PA flow was measured by an ultrasonic flow probe. PA mechanics were assessed by
      flow-pressure relations and by impedance spectra derived from flow and pressure
      waves. RV contractility was assessed by end-systolic elastance (Ees), RV
      afterload was assessed by effective PA elastance (Ea), and RV-PA coupling
      efficiency was assessed by the Ees:Ea ratio. Anesthetized dogs were randomly
      assigned to increasing concentrations (0.5, 1, and 1.5 times the minimum alveolar
      concentration) of isoflurane (n = 7) or desflurane (n = 7) in hyperoxia (fraction
      of inspired oxygen, 0.4) and hypoxia (fraction of inspired oxygen, 0.1). RESULTS:
      Isoflurane and desflurane had similar effects. During hyperoxia, both anesthetics
      increased PA resistance and characteristic impedance, increased Ea (isoflurane,
      from 0.82 to 1.44 mmHg/ml; desflurane, from 0.86 to 1.47 mmHg/ml), decreased Ees
      (isoflurane, from 1.09 to 0.66 mmHg/ml; desflurane, from 1.10 to 0.72 mmHg/ml),
      and decreased Ees:Ea (isoflurane, from 1.48 to 0.52; desflurane, from 1.52 to
      0.54) in a dose-dependent manner (all P < 0.05). Hypoxia increased PA resistance,
      did not affect characteristic impedance, increased afterload, and increased
      contractility. During hypoxia, isoflurane and desflurane had similar ventricular
      effects as during hyperoxia. CONCLUSIONS: Isoflurane and desflurane markedly
      impair RV-PA coupling efficiency in dogs, during hyperoxia and hypoxia, both by
      increasing RV afterload and by decreasing RV contractility.

PMID- 15564944
TI  - Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured
      astrocytes: an alternative protective mechanism.
AB  - BACKGROUND: The concentration of peroxynitrite in the brain increases after
      central nervous system injuries. The authors hypothesized that propofol, because
      of its particular chemical structure, mitigates the effects of peroxynitrite
      mediated oxidative stress and apoptosis by the induction of heme oxygenase (HO)-1
      in primary cultured astroglial cells. METHODS: Primary cultured astroglial cells
      were incubated for 18 h with a known peroxynitrite donor (3 mm SIN-1) in the
      presence or absence of propofol (40 microm, 80 microm, 160 microm, and 1 mm). The
      protective effects of propofol were evaluated by 3(4,5-dimethyl-thiazol-2-yl)2,5
      diphenyl-tetrazolium bromide cytotoxicity assay, lactic dehydrogenase release,
      DNA ladderization by Comet assay, and caspase-3 activation by Western blot
      analysis. RESULTS: Appropriate propofol concentrations (ranging from 40 microm to
      1 mm) significantly increased HO-1 expression and attenuated SIN-1-mediated DNA
      ladderization and caspase-3 activation. The protective effects of propofol were
      mitigated by the addition of tin mesoporphyrin, a potent inhibitor of HO
      activity. The addition of a specific synthetic inhibitor of nuclear factor kappaB
      abolished propofol-mediated HO-1 induction, suggesting a possible role of this
      nuclear transcriptional factor in our experimental conditions. CONCLUSIONS: The
      antioxidant properties of propofol can be partially attributed to its scavenging
      effect on peroxynitrite as well as to its ability to increase HO-1 expression at
      higher concentrations, a property that might be relevant to neuroprotection
      during anesthesia.

PMID- 15564945
TI  - Desflurane preconditioning induces time-dependent activation of protein kinase C
      epsilon and extracellular signal-regulated kinase 1 and 2 in the rat heart in
      vivo.
AB  - BACKGROUND: Activation of protein kinase C epsilon (PKC-epsilon) and
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) are important for
      cardioprotection by preconditioning. The present study investigated the time
      dependency of PKC-epsilon and ERK1/2 activation during desflurane-induced
      preconditioning in the rat heart. METHODS: Anesthetized rats were subjected to
      regional myocardial ischemia and reperfusion, and infarct size was measured by
      triphenyltetrazoliumchloride staining (percentage of area at risk). In three
      groups, desflurane-induced preconditioning was induced by two 5-min periods of
      desflurane inhalation (1 minimal alveolar concentration), interspersed with two
      10-min periods of washout. Three groups did not undergo desflurane-induced
      preconditioning. The rats received 0.9% saline, the PKC blocker calphostin C, or
      the ERK1/2 inhibitor PD98059 with or without desflurane preconditioning (each
      group, n = 7). Additional hearts were excised at four different time points with
      or without PKC or ERK1/2 blockade: without further treatment, after the first or
      the second period of desflurane-induced preconditioning, or at the end of the
      last washout phase (each time point, n = 4). Phosphorylated cytosolic PKC-epsilon
      and ERK1/2, and membrane translocation of PKC-epsilon were determined by Western
      blot analysis (average light intensity). RESULTS: Desflurane significantly
      reduced infarct size from 57.2 +/- 4.7% in controls to 35.2 +/- 16.7% (desflurane
      induced preconditioning, mean +/- SD, P < 0.05). Both calphostin C and PD98059
      abolished this effect (58.8 +/- 13.2% and 64.2 +/- 15.4% respectively, both P <
      0.05 versus desflurane-induced preconditioning). Cytosolic phosphorylated PKC
      epsilon reached its maximum after the second desflurane-induced preconditioning
      and returned to baseline after the last washout period. Both calphostin C and
      PD98059 inhibited PKC-epsilon activation. ERK1/2 phosphorylation reached its
      maximum after the first desflurane-induced preconditioning and returned to
      baseline after the last washout period. Calphostin C had no effect on ERK1/2
      phosphorylation. CONCLUSIONS: Both, PKC and ERK1/2 mediate desflurane-induced
      preconditioning. PKC-epsilon and ERK1/2 are both activated in a time dependent
      manner during desflurane-induced preconditioning, but ERK1/2 activation during
      desflurane-induced preconditioning is not PKC dependent. Moreover, ERK1/2
      blockade abolished PKC-epsilon activation, suggesting ERK-dependent activation of
      PKC-epsilon during desflurane-induced preconditioning.

PMID- 15564946
TI  - Combinations of bupivacaine, fentanyl, and clonidine for lumbar epidural
      postoperative analgesia: a novel optimization procedure.
AB  - BACKGROUND: The authors developed and applied a method to optimize the
      combination of bupivacaine, fentanyl, and clonidine for continuous postoperative
      lumbar epidural analgesia. METHODS: One hundred eighteen patients undergoing knee
      or hip surgery participated in the study. Postoperative epidural analgesia during
      48 h after surgery was optimized under restrictions dictated by side effects.
      Initially, eight combinations of bupivacaine, fentanyl, and clonidine (expressed
      as drug concentration in the solution administered) were empirically chosen and
      investigated. To determine subsequent combinations, an optimization model was
      applied until three consecutive steps showed no decrease in pain score. For the
      first time in a clinical investigation, a regression model was applied when the
      optimization procedure led to combinations associated with unacceptable side
      effects. RESULTS: The authors analyzed 12 combinations with an allowed
      bupivacaine concentration range of 0-2.5 mg/ml, a fentanyl concentration range of
      0-5 microg/ml, and a clonidine concentration range of 0-5 microg/ml. The best
      combinations of bupivacaine, fentanyl, and clonidine concentrations were 1.0
      mg/ml-1.4 microg/ml-0.5 microg/ml, 0.9 mg/ml-3.0 microg/ml-0.3 microg/ml, 0.6
      mg/ml-2.5 microg/ml-0.8 microg/ml, and 1.0 mg/ml-2.4 microg/ml-1.0 microg/ml,
      respectively, all producing a similarly low pain score. The incidence of side
      effects was low. The application of the regression model to combinations
      associated with high incidence of motor block successfully directed the
      optimization procedure to combinations within the therapeutic range. CONCLUSIONS:
      The results support further study of the combinations of bupivacaine, fentanyl,
      and clonidine mentioned above for postoperative analgesia after knee and hip
      surgery. This novel optimization method may be useful in clinical research.

PMID- 15564947
TI  - Probenecid interacts with the pharmacokinetics of morphine-6-glucuronide in
      humans.
AB  - BACKGROUND: Evidence obtained from porcine cell cultures and experiments in
      laboratory animals indicates that transmembrane transporters may play a role in
      the distribution of the active morphine metabolite morphine-6-glucuronide (M6G).
      This was evaluated in a study in healthy volunteers. METHODS: Ten subjects
      received an intravenous M6G infusion for 30 min at a dosage of 0.5 mg/kg body
      weight, leading to M6G plasma concentrations approximately two to three times
      higher than those observed with analgesic morphine doses in subjects with normal
      kidney function. In a randomized, double-blind, three-way crossover fashion,
      subjects received 800 mg quinidine for inhibition of P-glycoprotein; 500 mg
      probenecid for inhibition of other transporters, including organic anion
      transporter peptide, multidrug resistance-related protein, and organic anion
      transporter families; or placebo 1 h before the start of M6G administration.
      Plasma concentrations of M6G and pupil size were measured for 7 h. RESULTS:
      Probenecid pretreatment resulted in a decrease in the clearance of M6G from 8.3
      +/- 1 l/h to 6.7 +/- 1.3 l/h (factor of 0.8; P < 0.05 vs. placebo cotreatment).
      This was paralleled by an increase by a factor of 1.2 of the area under the
      miotic effect-versus-time curves (P < 0.05 vs. placebo). In contrast, quinidine
      pretreatment had no influence on the pharmacokinetics of M6G. CONCLUSIONS: The
      active morphine metabolite is subject to transmembrane transport by transporters
      inhibited by probenecid in humans.

PMID- 15564948
TI  - Chronic oral gabapentin reduces elements of central sensitization in human
      experimental hyperalgesia.
AB  - BACKGROUND: In chronic pain, increased activity from intact or damaged peripheral
      nerve endings results in an enhanced response in central pain transmission
      systems, a mechanism known as central sensitization. Central sensitization can
      also be invoked in human experimental models. Therefore, these models may be
      useful to characterize novel analgesics in humans. The anticonvulsant gabapentin
      has demonstrated efficacy in patients with neuropathic pain, but its mode of
      action remains unclear. This study examined the effects of gabapentin on signs of
      central sensitization (brush and pinprick hyperalgesia) in a human model of
      capsaicin-evoked pain, using a gabapentin dosing regimen similar to that used in
      the clinic. The aims were to determine whether gabapentin, dosed in a manner
      similar to that used in the clinic, affected the various components of central
      sensitization and to assess the utility of this model for characterizing novel
      analgesics. METHODS: Intradermal capsaicin (100 microg/20 microl) was
      administered in the volar forearm of 41 male human volunteers to induce pain and
      clinical signs of central sensitization. Gabapentin (titrated to 2,400 mg daily)
      or placebo was given orally for 15 days in a randomized, double-blind, parallel
      group design. The capsaicin test was conducted at baseline and after gabapentin
      or placebo. Endpoints were the size of areas of brush-evoked allodynia (with
      cotton gauze) and pinprick hyperalgesia (with von Frey filament), and the
      intensity of ongoing brush- and pinprick-evoked pain. RESULTS: Gabapentin
      significantly reduced the area of brush allodynia compared with placebo (P </=
      0.05) and insignificantly attenuated the area of pinprick hyperalgesia.
      Gabapentin had no significant effect on spontaneous and evoked pain intensity.
      CONCLUSION: Oral gabapentin, administered to healthy volunteers in a regimen
      similar to that used in treating chronic neuropathic pain, reduces measures of
      central sensitization evoked by intradermal capsaicin. This suggests that the
      pain-relieving effect in chronic neuropathic pain condition is linked to the
      effect of gabapentin on central sensitization. The ability of the capsaicin model
      to detect the efficacy of this standard treatment of neuropathic pain suggests
      that it may have a predictive value for detection of efficacy in human subjects.

PMID- 15564949
TI  - Effect of pain and audiovisual stimulation on the depression of acute hypoxic
      ventilatory response by low-dose halothane in humans.
AB  - BACKGROUND: The effects of different low-dose volatile agents in blunting the
      acute hypoxic ventilatory response (AHVR) are variable. Arousal (due to
      audiovisual stimulation) may prevent isoflurane-induced blunting of AHVR. The
      purpose of this study was to assess whether this was also the case for halothane.
      The authors also assessed the effects of pain on the interaction of halothane and
      AHVR. METHODS: Step decreases in end-tidal partial pressure of oxygen using
      dynamic end-tidal forcing were performed from normoxia to hypoxia (50 mmHg) in 10
      healthy volunteers, with end-tidal partial pressure of carbon dioxide held 1-2
      mmHg above normal, in six protocols: (1) control conditions (darkened, quiet
      room, eyes closed) without halothane and (2) with 0.1 minimum alveolar
      concentration (MAC) halothane; (3) audiovisual stimulation (bright room, loud
      television) without halothane and (4) with 0.1 MAC halothane; (5) pain
      (electrical stimulation of skin over the tibia to produce a visual analog pain
      score of 5-6 out of 10) without halothane and (6) with 0.1 MAC halothane. The
      Bispectral Index of the electroencephalogram was also monitored. RESULTS:
      Halothane did not affect normoxic minute ventilation in any arousal state but
      significantly reduced the magnitude of AHVR by 50% regardless of the background
      arousal state (P < 0.001). Bispectral Index values were reduced by halothane only
      in the absence of arousal (P < 0.003). Both pain and audiovisual stimulation
      modestly increased normoxic minute ventilation (P < 0.002) and AHVR (P < 0.003).
      CONCLUSIONS: Audiovisual stimulation does not prevent the blunting of AHVR by low
      dose halothane. This result with halothane differs from previous results with
      isoflurane. Therefore, different anesthetics interact in different ways with
      arousal states. This finding raises the possibility that different anesthetics
      might differentially affect the hypoxic chemoreflex loop or that they might act
      in the brain at sites separate from the chemoreflex loop, differently to
      influence the wakefulness drive to ventilation.

PMID- 15564950
TI  - Intranasal nicotine for postoperative pain treatment.
AB  - BACKGROUND: Despite pharmacological treatment, 70-80% of patients report moderate
      to severe pain after surgery. Because nicotine has been reported to have
      analgesic properties in animal and human volunteer studies, the authors assessed
      the analgesic efficacy of a single 3 mg dose of nicotine nasal spray administered
      before emergence from general anesthesia. METHODS: The authors conducted a
      randomized, double blind, placebo controlled trial of 20 healthy women (mean age
      45 (SD 8) yr) who were to undergo uterine surgery through a low transverse
      incision. After the conclusion of surgery but before emergence from general
      anesthesia, the anesthesiologist administered either nicotine nasal spray or a
      placebo. Numerical analog pain score and morphine utilization and hemodynamic
      values were measured for 24 h. RESULTS: The patients treated with nicotine
      reported lower pain scores during the first hour after surgery (peak numerical
      analog score, 7.6 (SD 1.4) versus 5.3 (SD 1.6); P < 0.001) and used half the
      amount of morphine as the control group (12 (SD 6) versus 6 (SD 5) mg; P < 0.05).
      Patients who received nicotine still reported less pain than those in the control
      group 24 h after surgery (1.5 (SD 0.5) versus 4.9 (SD 1.4); P < 0.01). Systolic
      blood pressure was lower in the group that received nicotine (105 (SD 3) versus
      122 (SD 3); P < 0.001), but there was no difference in diastolic blood pressure
      or heart rate. CONCLUSIONS: Treatment with a single dose of nicotine immediately
      before emergence from anesthesia was associated with significantly lower reported
      pain scores during the first day after surgery. The decreased pain was associated
      with a reduction in morphine utilization and the analgesic effect of nicotine was
      not associated with hypertension or tachycardia.

PMID- 15564951
TI  - Efficacy of a prophylactic epidural blood patch in preventing post dural puncture
      headache in parturients after inadvertent dural puncture.
AB  - BACKGROUND: Postdural puncture headache (PDPH) occurs in up to 80% of parturients
      who experience inadvertent dural puncture during epidural catheter placement. The
      authors performed a randomized double blind study to assess the effect of
      prophylactic epidural blood patch on the incidence of PDPH and the need for
      therapeutic epidural blood patch. METHODS: Sixty-four parturients who incurred
      inadvertent dural puncture were randomized to receive a prophylactic epidural
      blood patch with 20 ml autologous blood (prophylactic epidural blood patch group)
      or a sham patch (sham group). Subjects were evaluated daily for development of
      PDPH for a minimum of 5 days after dural puncture. Those who developed a PDPH
      were followed daily for a minimum of 3 days after resolution of the headache.
      Subjects with moderate headaches who reported difficulties performing childcare
      activities and all those with severe headaches were advised to receive a
      therapeutic epidural blood patch. RESULTS: Eighteen of 32 subjects in each group
      (56%) developed PDPH. Therapeutic blood patch was recommended in similar numbers
      of patients in each group. The groups had similar onset time of PDPH, median peak
      pain scores, and number of days spent unable to perform childcare activities as a
      result of postural headache. The median duration of PDPH, however, was shorter in
      the prophylactic epidural blood patch group. CONCLUSIONS: A decrease in the
      incidence of PDPH or the need for criteria-directed therapeutic epidural patch
      was not detected when a prophylactic epidural blood patch was administered to
      parturients after inadvertent dural puncture. However, prophylactic epidural
      blood patch did shorten the duration of PDPH symptoms.

PMID- 15564952
TI  - Epinephrine prevents muscle blood flow increases after perineural injection of
      tetrodotoxin.
AB  - BACKGROUND: The local anesthetic properties of tetrodotoxin, a potent naturally
      occurring sodium channel blocker, have been recently reexamined. It was found
      that sciatic nerve block duration could be greatly increased and systemic
      toxicity greatly decreased if epinephrine was injected with tetrodotoxin. The
      mechanism that underlies epinephrine-mediated prolongation of tetrodotoxin nerve
      blocks is not known, but indirect evidence suggests that epinephrine may slow the
      clearance of tetrodotoxin from the site of injection. The authors hypothesized
      that tetrodotoxin causes vasodilatation at its injection site, which accelerates
      its systemic uptake, and that this vasodilatation is attenuated by coinjected
      epinephrine. METHODS: The radiolabeled microsphere technique was used to measure
      tissue blood flow in anesthetized rats before and after perisciatic injection of
      tetrodotoxin alone and in combination with epinephrine. RESULTS: Tetrodotoxin, in
      a dose of 0.1 ml of a 60 microM solution, significantly increased blood flow in
      perisciatic muscle at the injected side compared with simultaneous contralateral
      control and ipsilateral preinjection baseline. Tetrodotoxin did not increase
      blood flow in the sciatic nerve. Coinjection of epinephrine with tetrodotoxin
      prevented tetrodotoxin-induced increases in perisciatic muscle blood flow over
      time and did not alter sciatic nerve blood flow. Arterial blood pressure was
      maintained with this dose of tetrodotoxin, although brain blood flow decreased.
      Coinjection of epinephrine with tetrodotoxin prevented decreases in brain blood
      flow. Higher doses of tetrodotoxin produced hypotension. CONCLUSIONS:
      Vasoconstriction in the perisciatic muscles by epinephrine may contribute to the
      prolongation of tetrodotoxin-induced sciatic nerve blocks and the reduction of
      systemic toxicity of tetrodotoxin.

PMID- 15564953
TI  - Effect of different cost drivers on cost per anesthesia minute in different
      anesthesia subspecialties.
AB  - BACKGROUND: Little is known about differences in costs to provide anesthesia care
      for different surgical subspecialties and which factors influence the
      subspecialty-specific costs. METHODS: In this retrospective study, the authors
      determined main cost components (preoperative visit, intraoperative personnel
      costs, material and pharmaceutical costs, and others) for 10,843 consecutive
      anesthesia cases from a 6-month period in the 10 largest anesthesia
      subspecialties in their university hospital: ophthalmology; general surgery;
      obstetrics and gynecology; ear, nose, and throat surgery; oral and facial
      surgery; neurosurgery; orthopedics; cardiovascular surgery; traumatology; and
      urology. Using regression analysis, the effect of five presumed cost drivers
      (anesthesia duration, emergency status, American Society of Anesthesiologists
      physical status of III or higher, patient age younger 6 yr, and placement of
      invasive monitoring) on subspecialty-specific costs per anesthesia minute were
      analyzed. RESULTS: Both personnel costs for anesthesiologists and total costs
      calculated per anesthesia minute were inversely correlated with the duration of
      anesthesia (adjusted R2 = 0.75 and 0.69, respectively), i.e., they were higher
      for subspecialties with short cases and lower for subspecialties with longer
      cases. The multiple regression model showed that differences in anesthesia
      duration alone accounted for the majority of the cost differences, whereas the
      other presumed cost drivers added only little to explain subspecialty-specific
      cost differences. CONCLUSIONS: Different anesthesia subspecialties show
      significant and financially important differences regarding their specific costs.
      Personnel costs and total costs are highest for subspecialties with the shortest
      cases. Other analyzed cost drivers had little effect on subspecialty-specific
      costs. In the light of these cost differences, a detailed cost analysis seems
      necessary before the profitability of an anesthesia subspecialty can be assessed.

PMID- 15564954
TI  - Making management decisions on the day of surgery based on operating room
      efficiency and patient waiting times.
AB  - The authors review the scientific literature on operating room management
      operational decision making on the day of surgery. (1) Some decisions should rely
      on the expected (mean) duration of the scheduled case. Other decisions should use
      upper prediction bounds, lower prediction bounds, and other measures reflecting
      the uncertainty of case duration estimates. One single number cannot be used for
      good decision making, because durations are uncertain. (2) Operational decisions
      can be made on the day of surgery based on four ordered priorities. (3) Decisions
      to reduce overutilized operating room time rely on mean durations. Limited
      additional data are needed to make these decisions well, specifically, whether a
      patient is in each operating room and which cases are about to finish. (4)
      Decisions involving reducing patient (and surgeon) waiting times rely on
      quantifying uncertainties in case durations, which are affected highly by small
      sample sizes. Future studies should focus on using real-time display of data to
      reduce patient waiting.

PMID- 15564955
TI  - Is low-dose haloperidol a useful antiemetic?: A meta-analysis of published and
      unpublished randomized trials.
AB  - The antiemetic efficacy of haloperidol was studied using data from 15 published
      (1962-1988) and 8 unpublished randomized trials; 1,397 adults received
      haloperidol, and 1,071 were controls. Settings were postoperative nausea or
      vomiting (1,994 patients), gastroenterology (261), chemotherapy (189), and
      radiation therapy (24). The relative benefit to prevent postoperative nausea or
      vomiting during 24 h with 0.5-4 mg haloperidol compared with placebo was 1.26
      1.51 (number needed to treat, 3.2-5.1), without evidence of dose responsiveness;
      0.25 mg was not antiemetic. With 1 mg haloperidol, the relative benefit to stop
      postoperative nausea or vomiting during 2-4 h compared with placebo was 1.53 (95%
      confidence interval, 1.17-2.00; number needed to treat, 6); with 2 mg, the
      relative benefit was 1.73 (1.11-2.68; number needed to treat, 4). In
      gastroenterology, 2 mg haloperidol was more effective than 1 mg. For chemotherapy
      and radiation therapy, no conclusions could be drawn. With 4 mg, one patient had
      extrapyramidal symptoms. With 5 mg, sedation was increased, with a relative risk
      of 2.09 (95% confidence interval, 1.73-2.52; number needed to treat, 4.4). There
      were no reports on cardiac toxicity. Postoperatively and in gastroenterology,
      haloperidol is antiemetic, with minimal toxicity. For other clinical settings and
      for children, valid data are unavailable.

PMID- 15564956
TI  - Severe thrombocytopenia, type 2B von Willebrand disease and pregnancy.

PMID- 15564957
TI  - Spinal epidural hematoma after spinal anesthesia in a patient treated with
      clopidogrel and enoxaparin.

PMID- 15564958
TI  - Transient profound neurologic deficit associated with thoracic epidural analgesia
      in an elderly patient.

PMID- 15564959
TI  - Sacral postherpetic neuralgia and successful treatment using a paramedial
      approach to the ganglion impar.

PMID- 15564960
TI  - Inhibition of sarcoplasmic Ca2+ adenosine triphosphatase in porcine skeletal
      muscle samples with cyclopiazonic acid enables in vitro malignant hyperthermia
      discrimination.

PMID- 15564961
TI  - Cardiac arrest, a preventable yet a possible risk of dexmedetomidine: fact or
      fiction?

PMID- 15564963
TI  - Prolonged wear of antichemical protective gear: the hazards and difficulties of
      wearing chemical warfare gear.

PMID- 15564965
TI  - Dexmedetomidine and asystole.

PMID- 15564966
TI  - Treatment of rebound pulmonary hypertension: why not sildenafil?

PMID- 15564967
TI  - Frequent utilization of fluoroscopy is essential for precise needle placement in
      interventional pain procedure.

PMID- 15564970
TI  - Regimens for patient-controlled epidural analgesia during labor.

PMID- 15564972
TI  - Cholinesterase inhibitors, neuromuscular blocking drugs and perioperative memory
      enhancement.

PMID- 15564973
TI  - Unanticipated difficult airway: what about emergency cases?

PMID- 15564974
TI  - Is it the validation or invalidation of the airway management algorithm?

PMID- 15564975
TI  - Use of a Fogarty catheter sheath as an endotracheal tube changer.

PMID- 15564977
TI  - Foreign body in the airway.

PMID- 15564978
TI  - Linezolid-bupropion interaction as possible etiology of severe intermittent
      intraoperative hypertension?

PMID- 15564979
TI  - Proceedings from the European Society of Hypertension Working Group on Blood
      Pressure Monitoring Scientific Workshop: What's New in Blood Pressure
      Measurement? June 2004, Paris, France.

PMID- 15564980
TI  - Blood pressure measurement and the guidelines: a proposed new algorithm for the
      diagnosis of hypertension.
AB  - Current hypertension guidelines continue to base management decisions on the
      office BP as recorded by mercury sphygmomanometry. The imminent disappearance of
      mercury from the workplace for environmental and safety reasons provides an
      opportunity to re-assess how a diagnosis of hypertension is made. There are now
      several validated, automated BP recording devices available to replace mercury
      sphygmomanometers in the office setting. Self/home and 24-hour ambulatory BP
      monitoring should now become an integral part of the diagnostic algorithm for
      hypertension in view of their superior ability to predict clinical outcomes when
      compared to traditional office BP measurements.

PMID- 15564981
TI  - Direct access ambulatory BP monitoring--the Edinburgh experience.
AB  - The use of electronic measurement of blood pressure and, in particular,
      ambulatory blood pressure monitoring offers the opportunity to determine which
      patients with apparent hypertension have truly sustained elevation of their blood
      pressure levels. Given the high prevalence of hypertension and the even larger
      number of individuals who appear to be hypertensive but may not be so, it is
      difficult to deliver ambulatory blood pressure monitoring to all individuals who
      might benefit from it. In Edinburgh, Scotland, we have piloted a system of direct
      access ambulatory blood pressure monitoring whereby physicians in primary care
      can request of the hospital service, an ambulatory monitor on their patient
      without the patients attending a formal hospital clinic. In the 7 years since the
      service was first instituted, almost 6,000 monitors have been performed with
      referrals running at approximately 100 per month in recent times. The present
      study was set up to assess the impact of the ambulatory monitor result on
      clinical decision making in primary care. The referral form invited primary care
      physicians to indicate their planned management if an ambulatory monitor had not
      been available and we thereafter audited patient records to determine what
      ultimately happened following the advice given on the basis of the ambulatory
      monitoring record.A random sample of results was obtained on untreated patients
      and approximately 500 were analysed. It was clear that if the advice to the
      primary care physician based upon the ABPM was not to treat, that this was
      largely followed with some 94% of patients not receiving treatment within 3
      months of the monitor. If, however, the advice given was to start treatment, this
      was less reliably followed and in only 76% of patients treatment was started
      within 3 months. At the time of the audit this figure had increased to 82%.
      Primary care physicians had indicated that they would have treated 60% of the
      individuals referred and in reality only treated 40%. The potential saving in
      drug costs from the reduction by 20% of those treated would have significant
      impact on health care budgets.

PMID- 15564982
TI  - Office and out-of-office blood pressure measurement in children and adolescents.
AB  - Office and out-of-office blood pressure measurements are being used for the
      diagnosis of hypertension in children and adolescents. The US National Heart,
      Lung, and Blood Institute have recently presented a new classification of blood
      pressure. On the basis of office measurements the 90th, 95th and 99th percentile
      for gender, age and height are used to classify children and adolescents as
      normotensive, pre-hypertensive and stage-1 or stage-2 hypertensive. Although
      auscultation using a standard mercury sphygmomanometer remains the recommended
      method, accumulating evidence suggests that ambulatory blood pressure monitoring
      is useful for the detection of white-coat hypertension and the prediction of
      target organ damage in children and adolescents. Studies have shown ambulatory
      blood pressure to be more reproducible than office measurements and normative
      tables for ambulatory measurements have been developed from cross-sectional
      studies in children and adolescents. In regard to home measurements in children,
      there are limited data from small trials showing lower blood pressure levels than
      daytime ambulatory blood pressure. In conclusion, ambulatory blood pressure
      monitoring is already finding a role as a supplementary source of information in
      children and adolescents, whereas at present home measurements should not be used
      for decision making in this population.

PMID- 15564983
TI  - Masked hypertension: how can the condition be detected?
AB  - Recent evidence demonstrates that masked hypertension is a significant predictor
      of cardiovascular disease, but the problem for clinical practice is how to
      identify these patients. Furthermore, the prevalence of masked hypertension in
      the general population or in subjects with transient blood pressure elevation is
      still unknown. Data obtained in several cross-sectional studies have demonstrated
      large differences in the prevalence of masked hypertension, with prevalence rates
      from a low of 8% to a high of 49%. Two population-based studies performed in
      Italy and in Japan report prevalence of 9% and of 13.4%, respectively. A 49%
      frequency of masked hypertension has been found among subjects with transiently
      elevated clinic blood pressure. Several factors can selectively raise ambulatory
      blood pressure including age, sex, smoking, alcohol use, contraceptive use in
      women, and sedentary habits. Reactivity to daily life stressors and behavioural
      factors are other important determinants of ambulatory blood pressure. On the
      basis of the available evidence, masked hypertension should be searched for in
      individuals who are more likely to have this condition or are at increased risk
      of cardiovascular complications including diabetic individuals and subjects with
      kidney disease. Further research is needed to determine whether the use of
      ambulatory blood pressure monitoring is cost-effective in these subjects.

PMID- 15564984
TI  - Detection of masked hypertension by home blood pressure measurement: is the
      number of measurements an important issue?
AB  - BACKGROUND: Office blood pressure (OBP) and home blood pressure (HBP) enable the
      identification of patients with masked hypertension. Masked hypertension is
      defined by normal OBP and high HBP and is known as a pejorative cardiovascular
      risk factor. OBJECTIVE: The objective was to evaluate in the SHEAF study the
      influence of the number of office or home blood pressure measurements on the
      classification of patients as masked hypertensives. METHODS: Patients with OBP
      <140/90 mmHg (mean of six values: three measurements at two separate visits, V1
      and V2) and HBP >135/85 mmHg (mean of all valid measurements performed over a 4
      day period) were the masked hypertensive reference group. The consistency of the
      classification was evaluated by using five definitions of HBP values (mean of the
      3, 6, 9, 12 and 15 first measurements) and two definitions of OBP values (mean of
      three measurements at V1 and mean of three measurements at V2). RESULTS: Among
      the 4939 treated hypertensives included in the SHEAF study, 463 (9.4%) were
      classified as masked hypertensives (reference group). By decreasing the number of
      office or home measurements, the prevalence of masked hypertension ranged from
      8.9-12.1%. The sensitivity of the classification ranged from 94-69% therefore 6
      31% of the masked hypertensives were not detected. The specificity ranged from 98
      94% therefore 1-6% of patients were wrongly classified as masked hypertensives.
      CONCLUSION: A limited number of home and office BP measurements allowed the
      detection of masked hypertension with a high specificity and a low sensitivity. A
      sufficient number of measurements (three measurements at two visits for OBP and
      three measurements in the morning and in the evening over 2 days for HBP) are
      required to diagnose masked hypertension.

PMID- 15564985
TI  - Determinants of white-coat hypertension.
AB  - BACKGROUND: The prevalence of white-coat hypertension (WCH) is considerable in
      patients referred with elevated office blood pressure. Failure to recognise this
      phenomenon can lead to the inappropriate use of antihypertensive medications. We
      undertook this study to determine the profile of patients with WCH. METHODS:
      Baseline clinic and daytime ambulatory blood pressures were available from 5716
      patients referred over a 22-year period. Individuals were considered to have WCH
      if they had an elevated clinic blood pressure measurement greater than 140/90
      mmHg and normal daytime mean ambulatory blood pressure. Mean age was 53.6 years
      and 53.2% were female. RESULTS: The overall prevalence of white-coat hypertension
      was 15.4%. A higher prevalence was seen amongst older adults, females, and non
      smokers. CONCLUSION: Multivariate logistic regression analysis confirmed these
      characteristics as independent predictors of WCH.

PMID- 15564986
TI  - Antihypertensive treatment based on home or office blood pressure--the THOP
      trial.
AB  - OBJECTIVE AND METHODS: In this randomized clinical trial, conducted in 400
      hypertensive patients [sitting diastolic blood pressure (DBP) >95 mmHg], blood
      pressure-lowering therapy was adjusted in a stepwise manner, either on the basis
      of the self-measured DBP at home or on the basis of conventional DBP measured at
      the doctor's office. RESULTS: Therapy guided by home blood pressure instead of
      office blood pressure led to less intensive drug treatment and marginally lower
      costs, but also to less blood pressure control with no differences in left
      ventricular mass. Self-measurement helped to identify patients with white-coat
      hypertension. CONCLUSIONS: The present findings support a stepwise strategy for
      the evaluation of blood pressure, in which self-measurement and ambulatory
      monitoring are complementary to conventional office blood pressure measurement.

PMID- 15564987
TI  - Prediction of ischaemic and haemorrhagic stroke by self-measured blood pressure
      at home: the Ohasama study.
AB  - OBJECTIVE: To examine the predictive value of self-measured blood pressure values
      taken at home (home blood pressure) for risk of stroke and subtypes. METHODS: We
      obtained home blood pressure measurements from 1702 people, aged > or =40 years,
      without a history of stroke, in the general population in Japan, and continued
      follow-up after a mean period of 10.6 years. The prognostic significance of blood
      pressure for stroke risk was examined using the Cox proportional hazards
      regression model, which was adjusted for possible confounding factors. RESULTS:
      There was a linear relationship between home blood pressure and risk of stroke
      and subtypes. On average, each 10/5 mmHg elevation in home systolic/diastolic
      blood pressure respectively, was associated with an approximately 30/20%
      respectively, higher risk of total stroke. A similar relationship was observed
      for the risk of haemorrhagic stroke (intracerebral and subarachnoid haemorrhage),
      and the risk of ischaemic stroke [cerebral infarction and transient ischaemic
      attack (TIA)]. The risk of stroke and subtypes showed a significantly greater
      relation with home blood pressure values compared to conventional blood pressure
      values. CONCLUSIONS: This is the first study to demonstrate that home blood
      pressure is an independent predictor for haemorrhagic and ischaemic stroke, in
      the general population.

PMID- 15564988
TI  - Telemonitoring of blood pressure self measurement in the OLMETEL study.
AB  - OBJECTIVE: To investigate the feasibility of blood pressure (BP) telemonitoring
      in previous uncontrolled hypertensives treated with olmesartan medoxomil in a
      clinical practice setting. METHODS: Patients (n = 53) with untreated,
      uncontrolled or insufficiently treated hypertension were selected by physicians
      to receive olmesartan medoxomil 10-40 mg/day for 12 weeks. Office BP values were
      determined by a physician at baseline and after 12 weeks' treatment; BP self
      measurement (BPSM) was conducted throughout the 12-week treatment period using a
      TensioPhone TP2 telemonitoring device; BP values were stored and automatically
      downloaded to a remote service centre via standard telephone lines. RESULTS:
      Olmesartan medoxomil produced statistically significant reductions from baseline
      in both systolic and diastolic office BP and BPSM values. In contrast to office
      BP, telemonitoring of BPSM allowed the early identification of responders (e.g.,
      after 2-3 weeks' treatment). Blood pressure reduction with olmesartan medoxomil
      was greater for office BP than for BPSM values. Normalization of BP was achieved
      in 64.2% of the patients using office BP measurement compared with 36.4% using
      BPSM. Blood pressure self-measurement showed no significant difference between
      morning and evening BP measurements or between the morning : evening BP ratio at
      baseline and after nine weeks of olmesartan medoxomil treatment. Compliance and
      tolerability were good or very good in most patients. CONCLUSION: In a 'real
      life' clinical practice setting, telemonitoring of BPSM was an effective
      technique that was partially affected by patient non-compliance. Olmesartan
      medoxomil provided effective and reliable BP-lowering, which was maintained
      throughout the 24-hour period.

PMID- 15564989
TI  - Mental health services need a more positive image.

PMID- 15564990
TI  - The worldwide burden of COPD is on the increase.

PMID- 15564991
TI  - Current practice in administration of parenteral nutrition: venous access.
AB  - Today, there are many alternative feeding options for patients unable to eat and
      drink and nutrition support has become part of everyday clinical practice.
      Although feeding via the enteral route used to be considered optional, recent
      experts have re-examined the role of parenteral nutrition, and found it to be as
      beneficial. This article will review current practice surrounding parental
      nutrition, its indications and the associated complications. Successful feeding
      via the intravenous route relies on the selection of the appropriate intravenous
      access, optimum nursing care and close patient monitoring. The range of venous
      access options will be discussed and advantages and disadvantages identified.

PMID- 15564992
TI  - Dietary pattern of self-care among Asian and Caucasian diabetic patients.
AB  - Diabetes mellitus is a growing pandemic and its self-care management rests
      primarily with the individual. This qualitative case study investigated the self
      care dietary pattern among a group of 25 Asians and 24 Caucasians diagnosed with
      type 1 or type 2 diabetes. Data collected from a semi-structured interview and a
      7-day health diary explored the self-care activities undertaken by the
      participants to establish metabolic control. From an analytical perspective, the
      collective responses were placed on a continuum ranging from strict adherence,
      moderately flexible adherence to very flexible adherence. The findings suggest
      that most of the participants were located in the latter two categories of diet
      related to self-care. Implications for healthcare professionals in promoting self
      care will be discussed.

PMID- 15564993
TI  - Healthcare professionals' knowledge of motor neurone disease.
AB  - Healthcare professionals have a professional duty to provide patients with
      accurate information in order to assist in managing their illness. This may be
      more difficult with an uncommon illness, such as motor neurone disease (MND), as
      many healthcare professionals may feel poorly informed about the illness
      themselves. This study set out to survey the level of knowledge and understanding
      about MND among a group of 100 healthcare professionals who had personal
      experience of managing the care of a person with MND. The value of the MND nurse
      specialist and the Motor Neurone Disease Association as sources of information
      were highlighted. There was evidence of active information-seeking about MND
      among all professional groups. However, while many respondents felt that their
      knowledge of the disease processes in MND and their own profession's role in the
      management of the condition was good, 57% of respondents felt that their current
      level of overall knowledge about MND was inadequate.

PMID- 15564994
TI  - Clinical skills: a care plan approach to nurse-led extubation.
AB  - Long-term mechanical ventilation (in patients who require mechanical ventilation
      for longer than 24 hours) has been associated with prolonged anxiety, chest
      infections and high mortality rates. Prolonged mechanical ventilation is also
      costly, as it tends to be carried out in critical care environments which require
      high levels of staffing. Therefore, it would appear to be of great benefit to
      patients, relatives and all multidisciplinary healthcare professionals concerned
      in delivering respiratory care if patient ventilation was kept as brief as
      possible. Current opinions seem to suggest that nurses can be the key players in
      reducing the time on a mechanical ventilator for patients and can take the lead
      on the extubation process of ventilatory weaning.

PMID- 15564995
TI  - Nurse manager who was rude to staff and lied about his qualifications.

PMID- 15564996
TI  - The nursing role in recognizing and assessing neuropathic pain.
AB  - Neuropathic pain is suffered by approximately 1% of the UK population and poses a
      vast socio-economic problem through unemployment and expenditure on medical and
      social services. It also presents a major therapeutic challenge to healthcare
      professionals, since it can be difficult to recognize and to treat. With the
      advent of new and effective medications, the prognosis for patients can be
      significantly improved by early recognition and aggressive therapy. This article
      aims to equip nurses with the assessment skills to identify neuropathic pain and
      a basis from which to expedite pain relief through appropriate intervention and
      referral within the multidisciplinary team.

PMID- 15564997
TI  - NICE guidelines: the management, treatment and care of COPD.
AB  - Over a year ago the National Institute for Clinical Excellence (NICE)
      commissioned national guidelines for managing chronic obstructive pulmonary
      disease (COPD) in both primary and secondary care. The resulting guidelines
      published earlier this year are the result of a systematic review of the evidence
      in the published literature and where this has not been available expert opinion
      has informed recommendations. The document makes over 200 recommendations for
      practice with seven key areas where it was felt that implementation of the
      recommendations would have the largest impact on the management of COPD. The
      result is a comprehensive document concentrating on the health aspects of COPD
      and the following article looks at the guidelines and concentrates on the seven
      priority areas.

PMID- 15564998
TI  - The refusal of treatment: living wills and the current law in the UK.
AB  - David Browne was suffering from motor neurone disease and was anxious to ensure
      that as his disease progressed and he ceased to be mentally capacitated he would
      not be given artificial feeding and ventilation. He therefore arranged to draw up
      a living will in which he gave an advanced refusal of such treatments. The
      document was duly signed and witnessed. Only 3 months after signing the living
      will he was severely injured in a road accident and brought into hospital
      unconscious. He was carrying his living will in his pocket. The doctors were
      concerned that if they operated and he required ventilation in intensive care,
      would the living will prevent their providing such treatment and care? What is
      the law?

PMID- 15564999
TI  - Managing and caring for a patient with a complicated wound.
AB  - The patient discussed in this care study is a 91-year-old woman admitted to
      hospital from her own home. She presented with reduced mobility, constipation,
      increased confusion and reduced oral intake. Her history included small vessel
      disease and a stroke. On admissions she also had a number of grade two pressure
      ulcers on her buttocks. The surrounding skin appeared macerated and the patient
      complained of pain when the skin was cleaned after she was incontinent of both
      urine and faeces. It was expected that the wound would be fast healing, as it was
      superficial, but the healing rate proved otherwise. This article will focus on
      incontinence management as well as ways of aiding in healing a pressure ulcer
      where skin is macerated and the patient has many risk factors.

PMID- 15565000
TI  - How to run an efficient and safe nurse-led service.

PMID- 15565001
TI  - [Usefulness of MR diffusion imaging for evaluating brain tumors].

PMID- 15565002
TI  - [Fundamentals of liquid crystal displays and its recent technology].

PMID- 15565003
TI  - [Many ethical problems which encounter in the clinical spot].

PMID- 15565004
TI  - [Ultrasound examination of superficial organs].

PMID- 15565006
TI  - [The cross-calibration for plane-parallel chambers in electron beams].

PMID- 15565009
TI  - [X-ray Protection Construction Standardization Manual -Part 5-].

PMID- 15565010
TI  - [Survey and analysis of radiation safety education at radiological technology
      schools].
AB  - We carried out a questionnaire survey of all radiological technology schools, to
      investigate the status of radiation safety education. The questionnaire consisted
      of questions concerning full-time teachers, measures being taken for the
      Radiation Protection Supervisor Qualifying Examination, equipment available for
      radiation safety education, radiation safety education for other departments,
      curriculum of radiation safety education, and related problems. The returned
      questionnaires were analyzed according to different groups categorized by form of
      education and type of establishment. The overall response rate was 55%, and there
      were statistically significant differences in the response rates among the
      different forms of education. No statistically significant differences were found
      in the items relating to full-time teachers, measures for Radiation Protection
      Supervisor Qualifying Examination, and radiation safety education for other
      departments, either for the form of education or type of establishment. Queries
      on the equipment used for radiation safety education revealed a statistically
      significant difference in unsealed radioisotope institutes among the forms of
      education. In terms of curriculum, the percentage of radiological technology
      schools which dealt with neither the shielding calculation method for radiation
      facilities nor with the control of medical waste was found to be approximately
      10%. Other educational problems that were indicated included shortages of full
      time teachers and equipment for radiation safety education. In the future, in
      order to improve radiation safety education at radiological technology schools,
      we consider it necessary to develop unsealed radioisotope institutes, to appoint
      more full-time teachers, and to educate students about risk communication.

PMID- 15565011
TI  - [Efficacy of three-dimensional image fusion of lymphoscintigraphy and MDCT data
      sets in breast cancer].
AB  - The aim of this study was to evaluate the clinical usefulness of image fusion of
      lymphoscintigraphy with (99m)Tc phytate and volume-rendering images generated by
      multidetector-row CT (MDCT) in patients with breast cancer. The subjects were 25
      patients with clinically negative nodes. Data from the two imaging modalities
      were fused on a personal computer. Thirty-five axillary sentinel nodes were
      identified by lymphoscintigraphy. The anatomical locations of sentinel nodes in
      27 patients were clearly demonstrated by 3D-fusion imaging (84%). Image fusion of
      lymphoscintigraphy with (99m)Tc phytate and volume-rendering images is helpful
      for sentinel node biopsy in breast cancer.

PMID- 15565012
TI  - [Performance evaluation of X-ray CT using visible scintillation light].
AB  - We proposed a new method of performance evaluation for X-ray CT using visible
      scintillation light and examined its usefulness in this study. When we scanned a
      plastic scintillator disk in a gantry opening of the X-ray CT, we could observe
      visible scintillation light. The rotation of the light-emitting area of the disk
      corresponded to that of the X-ray tube. We were able to record the scintillation
      light by digital video camera. By analyzing the area of visible scintillation
      light, the rotation speed of the X-ray tube, angular spread of the X-ray beam,
      uniformity of the incident X-rays, and change in X-ray energy were measured. No
      other method is available to obtain the above parameters of X-ray CT during a
      single CT scan. In the measurements of the uniformity of incident X-rays and
      change of X-ray energy, our method showed good accuracy in detecting the
      attenuation caused by the couch between the X-ray tube and the plastic
      scintillator disc. The proposed method is inexpensive and easy-to-use. We
      conclude that the method is a useful tool for performance evaluation as well as a
      maintenance tool for X-ray CT.

PMID- 15565013
TI  - [Fundamental study of magnetization transfer contrast (MTC) effect: optimization
      of MT pulse condition using experimental phantom].
AB  - Magnetization transfer contrast (MTC) was evaluated by changing the off-set
      frequency and pulse intensity of MTC with the spoiled gradient echo (SPGR)
      sequence (T2*-weighted image) using an experimental phantom that included olive
      oil, protein, fiber, collagen, and pure water. The intensity of pure water
      reached a constant level just above the off-set frequency (1200 Hz) regardless of
      MT pulse power. The contrast-to-noise ratio (CNR) in each of the phantom
      materials was maximal at the MT pulse power of 2500 degrees (equivalent flip
      angle). The CNR and image noise obtained by body coil were inferior to those
      obtained with an extremity coil. In clinical application, the MTC effect on
      chondrosarcoma was higher (MT ratio, ROI-1:0.448, ROI-2:0.382) than those of
      other cases in this study. Since the image contrast was improved between the
      malignant fibrous histiocytoma (MFH, MT ratio, ROI-1:0.282, ROI-2:0.289) and
      peripheral tissues, extraskeletal extension could be observed more easily than
      without MTC imaging. In conclusion, the effects of MTC might be in providing
      useful information, in presuming composed tissues, differential diagnoses, and
      extent to the surrounding structures because of changing the image contrast to
      surrounding tissues corresponding to the rate of included bound water.

PMID- 15565014
TI  - [Evaluation of positioning reproducibility using a re-locatable head frame for
      stereotactic radiotherapy].
AB  - In fractionated stereotactic radiotherapy (SRT), the accuracy of patient
      relocation is very important. The Gill-Thomas-Cosman (GTC) re-locatable
      stereotactic frame is used for patient immobilization. A depth helmet and
      measuring probe are used to check the stability of the patient's head position
      relative to the GTC frame. However, displacement error caused by rotation of the
      patient's head is not considered in the depth-helmet measurement. Consequently,
      displacement of the isocenter position cannot be confirmed by the measurement
      obtained from the depth helmet. In this study, we evaluated the precision of
      reproducibility by comparing measurement values of the depth helmet with the
      displacement of anatomical position on a CT image. We analyzed 21 setups of 8
      patients immobilized for SRT using the GTC frame, between June 2001 and June
      2003. The reproducibility of the GTC frame was checked at each treatment by
      comparing it with the treatment planning position. The average discrepancy of the
      GTC frame set-up measured by the depth helmet was 0.6 mm, with a standard
      deviation of 0.3 mm. The result measured by CT was 0.7 mm, with a standard
      deviation of 0.4 mm. When the error of each measurement point was within 1.0 mm,
      the accuracy of relocation of the patient could be considered clinically
      acceptable. Displacement error not considered in the measurement of the depth
      helmet could be evaluated by using CT.

PMID- 15565015
TI  - [Measurement of the humeral retroversion angle using a simple X-ray pictorial
      image].
AB  - The semi-axial-view method is used to measure humeral retroversion angles by a
      single x-ray exposure. We examined the clinical utility of this method using a
      humerus model and normal volunteers. In an experiment with a humerus model,
      humeral retroversion angles were measured at various positioning angles by the
      semi-axial-view method, and compared with the angles measured by the CT method,
      which is considered the standard, and the best position was determined. The upper
      arms of three volunteers were photographed by the semi-axial-view method in the
      most suitable position, and humeral retroversion angles were compared with those
      obtained by the CT method. As a result of examination with a humerus model, the
      best positioning angles were 20 degrees of shoulder abduction angle, 90 degrees
      of shoulder flexion angle, and 90 degrees of elbow flexion angle. There were no
      significant differences between the humeral retroversion angles of the CT and
      semi-axial-view methods with the best position determined in volunteers. In
      conclusion, the semi-axial-view method is a useful, easy method for measuring the
      humeral retroversion angle. This method will be a great asset in researching
      large numbers of samples.

PMID- 15565016
TI  - Development of an ultrasound training phantom of the thyroid gland: physical
      characteristics of TMM.
AB  - The objective of this research was to synthesize a thyroid phantom with
      ultrasound properties similar to those of tissue-mimicking materials (TMM). This
      was done so that an ultrasound thyroid-training phantom could be developed. A
      polymer urethane TMM was made by using the following materials: C, CCR, TiO(2),
      silver, tungsten, and graphite, in the hope that it would have the same
      properties as soft tissue. To confirm this similarity, several tests were
      undertaken, including penetration, gray scale, propagated speed, and attenuation
      back comparison. The results of this study were as follows: (1) The propagated
      speed of C, CCR, and graphite-type TMM were 1,460-1,580 m/s. Attenuation was 0.5
      0.7 dB/cm/MHz, and a homogeneous echo pattern similar to that of thyroid gland
      was noted. (2) The TiO(2) TMM seemed similar to that of thyroid even in low echo.
      The surrounding area also showed similar patterns. (3) The silver TMM showed an
      echo pattern similar to that of prostate. (4) The tungsten TMM showed a visible
      heterogeneous echo pattern. (5) The C-type TMM was compared with human thyroid
      and also tested via ultrasound imaging. It is hoped that this research will be
      useful in the future in ultrasonography training and in providing a better
      thyroid-training phantom and phantoms of other organs.

PMID- 15565017
TI  - Introduction of routine HIV testing in prenatal care--Botswana, 2004.
AB  - In 2003, approximately 37% of pregnant women in Botswana (2001 population: 1.7
      million; approximately 40,000 births per year) were infected with human
      immunodeficiency virus (HIV). Since 2001, all prenatal clinics in Botswana have
      offered HIV screening and interventions for prevention of mother-to-child
      transmission of HIV (PMTCT), which can decrease vertical transmission of HIV from
      35%-40% to 5%-10%. Historically, HIV testing in Botswana has been performed after
      individual pretest counseling, with patients actively choosing whether to be
      tested (i.e., an "opt-in" approach). In 2003, 52% of pregnant women receiving
      prenatal care nationwide learned their HIV status. In 2004, to increase use of
      free national PMTCT and antiretroviral treatment (ARV) programs, Botswana began
      routine, noncompulsory (i.e., "opt-out") HIV screening in prenatal and other
      health-care settings. Concerns have been raised that routine testing in Africa
      might deter women from seeking prenatal care and might result in fewer women
      returning for their test results and HIV care after testing. To assess the early
      impact of routine testing on HIV-test acceptance and rates of return for care,
      the CDC Global AIDS Program and the PMTCT program in Botswana evaluated routine
      prenatal HIV testing at four clinics in Francistown, the second largest city in
      Botswana, where HIV prevalence has been > or =40% since 1995. This report
      describes the results of that assessment, which indicated that, during February
      April 2004, the first 3 months of routine testing, 314 (90.5%) of 347 pregnant
      women were tested for HIV, compared with 381 (75.3%) of 506 women during October
      2003-January 2004, the last 4 months of the opt-in testing period (p<0.001).
      However, many women who were tested never learned their HIV status because of
      logistical problems or not returning to the clinic. Substantial increases in HIV
      testing of pregnant women were also observed at the Francistown referral hospital
      and at prenatal clinics nationwide. These findings highlight the potential public
      health impact of routine HIV testing with rapid, same-day results for programs
      seeking to increase the number of persons with access to HIV-prevention and
      treatment services.

PMID- 15565018
TI  - Two cases of Hantavirus pulmonary syndrome--Randolph County, West Virginia, July
      2004.
AB  - Hantavirus pulmonary syndrome (HPS) is a rare cardiopulmonary disease caused by
      viruses of the genus Hantavirus, for which rodents are the natural reservoir.
      Transmission to humans occurs by direct contact with rodents or their excreta or
      by inhalation of aerosolized infectious material (e.g., dust created by
      disturbing rodent nests). In July 2004, HPS cases (including one fatal case) were
      reported in two persons believed to have been exposed at sites approximately 12
      miles apart in Randolph County, West Virginia (2000 population: 28,254). This
      report describes the two cases and summarizes their epidemiologic and
      environmental investigations. Clinicians and the public need to be educated about
      the risk for HPS and methods to reduce that risk.

PMID- 15565019
TI  - Serious psychological distress among persons with diabetes--New York City, 2003.
AB  - "Depression, anxiety, and other disorders causing serious psychological distress
      (SPD) frequently complicate the health care of persons with diabetes." To assess
      the prevalence and effects of SPD among adults with diabetes, the New York City
      Department of Health and Mental Hygiene (DOHMH) analyzed data from approximately
      10,000 adults who participated in the 2003 New York City Community Health Survey
      (CHS). The results indicated that 1) adults with diabetes were twice as likely to
      have SPD as those without diabetes, and 2) adults with both SPD and diabetes were
      more likely than those with only diabetes to live in poverty, report poor health,
      lack access to health care, and to have lost a spouse or partner to separation,
      divorce, or death. An integrated program of physical and mental health care that
      addresses socioeconomic barriers and improves access to treatment might improve
      the overall health of persons with diabetes and SPD.

PMID- 15565030
TI  - "Secret patients": a dangerous, demoralizing practice.

PMID- 15565031
TI  - Retaining older ED nurses.

PMID- 15565032
TI  - Trismus and acute respiratory distress in a 63-year-old woman ten days after
      stepping on a firecracker.

PMID- 15565033
TI  - Blood samples drawn from IV catheters have less hemolysis when 5-mL (vs 10-mL)
      collection tubes are used.
AB  - INTRODUCTION: It is common practice for emergency nurses to draw blood for
      laboratory analyses into vacuum tubes from newly inserted intravenous (IV)
      catheters, even though this technique has been associated with an increase in
      sample hemolysis. No clinical nursing studies have documented the effect of
      collection tube size on hemolysis of samples obtained via IV catheters.
      OBJECTIVE: To determine whether there is a difference in the hemolysis rate of
      blood samples drawn from IV catheters comparing 5-mL vacuum collection tubes to
      10 mL vacuum collection tubes. SETTING: The study was conducted at the Emergency
      Department, Summa Health System, Akron, Ohio. Method This study used a 4-group, 2
      period crossover design randomly assigning the order of the vacuum tube drawn.
      With the crossover design, each patient served as his own control. Upon receiving
      orders to start an IV and draw blood, each of 12 study nurses obtained an
      envelope with 2 vacuum tubes randomly assigned as to which tube should be drawn
      first and which tube should be drawn second. Samples were analyzed for hemolysis
      using a Hitachi automated spectrophotometer as well as by visual inspection. DATA
      ANALYSIS: A linear mixed model was used to test the main hypothesis of vacuum
      tube type effects on hemolysis. RESULTS: The 5-mL tubes showed significantly
      lower hemolysis than the 10 mL tubes ( P <.0001) with a substantial effect size
      of .6 standard deviation units. CONCLUSION: The risk of hemolyzing blood drawn
      from IV catheters can be significantly reduced by using 5-mL rather than 10-mL
      collection tubes.

PMID- 15565034
TI  - A comparison of five state trauma systems meeting all eight essential ACS
      criteria: a descriptive survey.

PMID- 15565035
TI  - Moose and other large animal wildlife vehicle collisions: implications for
      prevention and emergency care.

PMID- 15565039
TI  - Death by syringe.

PMID- 15565040
TI  - Family presence during a failed major trauma resuscitation attempt of a 15-year
      old boy: lessons learned.

PMID- 15565043
TI  - A 74-year-old woman with numbness and paralysis of legs, no discernable femoral
      pulses, and pain in her lower back.

PMID- 15565044
TI  - Treating diabetic ketoacidosis in children while preventing cerebral edema: one
      hospital's protocol.

PMID- 15565045
TI  - The coma cocktail: indications, contraindications, adverse effects, proper dose,
      and proper route.

PMID- 15565046
TI  - Advancing justice for sexual assault survivors and innocent inmates, or threat to
      privacy? A controversial DNA technology proposal.

PMID- 15565047
TI  - Recognizing excellence in nursing service: a first-hand report from an ED manager
      at a magnet hospital in Boston. Interview by Iris Frank.

PMID- 15565048
TI  - 2003 "clarification" of controversial EMTALA requirement for 24/7 coverage of
      emergency departments by on-call specialists, significant impact on trauma
      centers.

PMID- 15565049
TI  - A look at a two-step triage system: "How one high volume, level I trauma center
      decreased long triage waits".

PMID- 15565066
TI  - New food selections provide opportunities and challenges.

PMID- 15565067
TI  - Facing racial and ethnic health disparities.

PMID- 15565068
TI  - A place at the table: marketing dietetics professionals' expertise to other
      health care providers in a clinical setting.

PMID- 15565069
TI  - Growing policy with grassroots activism.

PMID- 15565070
TI  - Effectiveness of medical nutrition therapy: importance of documenting and
      monitoring nutrition outcomes.

PMID- 15565071
TI  - Diets lower in folic acid and carotenoids are associated with the coronary
      disease epidemic in Central and Eastern Europe.
AB  - OBJECTIVE: To test our hypothesis that lower intakes of previously identified
      cardioprotective nutrients would be associated with the coronary epidemic in
      Central and Eastern Europe. DESIGN: We conducted a survey of coronary mortality
      in 16 countries and diet in 19 countries. SUBJECTS/SETTING: Countries were placed
      in four groups with different cultural patterns (Central and Eastern Europe,
      including Russia; Western Europe and the United States; Mediterranean; and
      Asian). MAIN OUTCOME MEASURES: Independent predictors of coronary mortality.
      STATISTICAL ANALYSES PERFORMED: Means and standard deviations were calculated,
      and analysis of variance with Bonferroni post hoc tests and backward elimination
      regression analysis was conducted. RESULTS: Coronary mortality was highest in
      Central and Eastern Europe followed by Western Europe and the United States, the
      Mediterranean countries, and Asia (Japan). The model with folate, fiber, and n
      6/n-3 fatty acids explained the majority of variation in coronary mortality (men
      86%, women 90%). Most of the variation was explained by folate (men 61%, women
      62%). The picture is complicated by the fact that folate, lutein/zeaxanthin, and
      beta-carotene were highly intercorrelated ( r =0.87 to 0.99). CONCLUSIONS: A diet
      low in foods containing folate and carotenoids (beta-carotene and
      lutein/zeaxanthin) may be a major contributing factor to increased coronary risk
      observed in the countries of Central and Eastern Europe.

PMID- 15565072
TI  - Glycemic and insulinemic responses to protein supplements.
AB  - OBJECTIVE: The effects of common servings of commercially marketed nutritional
      protein supplements on blood glucose and insulin responses were studied in 12
      healthy men after ingestion of feedings that had varying carbohydrate and protein
      compositions. DESIGN: Fasting subjects consumed a 50-gram glucose drink, a white
      bagel, peanuts, a protein bar, or a protein drink in a counterbalanced fashion.
      SETTING: Subjects rested in a supine position and were not disturbed while blood
      samples were drawn at rest and at 10-minute intervals during the ensuing 2 hours.
      RESULTS: The area under the curve for glucose was greater in the glucose drink
      group vs all treatment groups except the white bagel group ( P <.05). At 20 to 40
      minutes, plasma glucose was elevated in the glucose drink group vs the peanuts
      group, the protein bar group, and the protein drink group ( P <.05). The glycemic
      response was greater in the glucose drink group vs the white bagel group at 30
      minutes (8.1+/-0.5 vs 6.5+/-0.3 mmol/L, respectively) ( P <.05). The area under
      the curve for insulin was lower in the peanuts group vs all treatment groups ( P
      <.05). Insulin concentrations peaked at 40 minutes in the glucose drink group
      (285.5+/-18.3 pmol) and was similar in all but the peanuts group (130.5+/-14.3
      pmol) ( P <.05). CONCLUSIONS: A common serving of a commercially available
      protein supplement resulted in a marked insulin response with no glycemic
      response because of the lack of carbohydrate content. Inasmuch as many such
      supplements similar in composition are marketed on the bases of their nutritional
      energy benefits, these data underscore the need to educate consumers regarding
      appropriate fuel for exercise and nutritional supplement composition.

PMID- 15565073
TI  - Feeding the athlete.

PMID- 15565074
TI  - Outcomes monitoring of health, behavior, and quality of life after nutrition
      intervention in adults with type 2 diabetes.
AB  - OBJECTIVES: To examine changes in health and lifestyle indicators over 6 months
      in persons with type 2 diabetes mellitus receiving nutrition counseling from a
      registered dietitian, and to promote dietetics professionals' participation in
      outcomes monitoring and research. DESIGN: Prospective, noncontrolled descriptive
      study. SUBJECTS: Two hundred forty-four physician-referred adults with type 2
      diabetes mellitus from 31 sites who received usual and customary nutrition
      counseling, and 83 registered dietitians. MAIN OUTCOME MEASURES: Glycemic
      control, coronary heart disease risk, self-management behaviors, and quality of
      life were measured at baseline, 3 months, and 6 months. Dietitians' perceptions
      of the study were also measured. STATISTICAL ANALYSIS: Repeated-measures analysis
      of variance, paired t test, Wilcoxon signed rank test, sign test, Spearman
      correlation, and chi 2 analysis were conducted. RESULTS: Weight and glycemic
      control, coronary heart disease risk, and self-management behaviors improved
      significantly between baseline and 3 months and baseline and 6 months. Weight,
      body mass index, and glycosylated hemoglobin value also improved significantly
      between 3 months and 6 months. Increased time and/or number of sessions with the
      registered dietitian were associated with weight loss and reduced glycosylated
      hemoglobin, fasting plasma glucose, total cholesterol, and triglyceride levels.
      Self-perceived health status and missed workdays were significantly improved at 6
      months. Difficulty obtaining current laboratory values, lack of time, and
      inability to reach subjects for follow-up presented the greatest obstacles for
      the dietitians. CONCLUSIONS: Positive outcomes were observed in adults receiving
      nutrition intervention for type 2 diabetes. Clinical improvements were greatest
      between baseline and 3 months, with stabilization between 3 months and 6 months,
      suggesting ongoing intervention is needed to support continued clinical progress.
      Dietitians found participation in this state affiliate-coordinated research
      project rewarding.

PMID- 15565075
TI  - Food frequency questionnaire results correlate with metabolic control in insulin
      treated veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study.
AB  - OBJECTIVE: To validate food frequency analysis as a predictor of metabolic status
      in persons with type 2 diabetes and to identify psychosocial factors affecting
      dietary adherence. METHODS: Three hundred forty-seven subjects with stable,
      insulin-treated type 2 diabetes completed a food frequency questionnaire and six
      instruments measuring different psychosocial attributes. Eight metabolic
      parameters were used as principal endpoints. Data from the food frequency
      questionnaires were used to estimate daily energy intake and determine each
      subject's adherence to seven dietary standards derived from the 2003 Dietary
      Recommendations of the American Diabetes Association. We excluded 105 subjects
      reporting daily energy intake <1,000 kcal because these results were considered
      unreliable. Subjects were then categorized into three groups depending on their
      adherence rates to American Diabetes Association dietary standards. RESULTS:
      Subjects with the lowest dietary adherence had the poorest metabolic control.
      Adherence to dietary standards was particularly poor among subjects with
      metabolic syndrome (2.1%) and/or obesity (4.1%). The most important determinants
      of following recommended dietary practices were positive attitudes, fewer social
      barriers, and a conviction that diet could control diabetes. CONCLUSIONS: For
      subjects with type 2 diabetes reporting a dietary intake of >1,000 kcal/day, food
      frequency questionnaire data could identify those with poor metabolic control.
      Nutrition interventions to improve metabolic control should focus on reducing fat
      intake and emphasizing the importance of diet. Multidisciplinary efforts should
      be directed at overcoming social barriers to recommended dietary practices and to
      treating depression.

PMID- 15565076
TI  - A possible quick-assessment tool for patients with diabetes.

PMID- 15565077
TI  - More favorable dietary patterns are associated with lower glycemic load in older
      adults.
AB  - OBJECTIVE: Glycemic load represents the total glycemic effect of the diet and may
      reduce the risk for chronic disease by affecting the risk for obesity and by
      altering metabolic endpoints. The food choices associated with lower-glycemic
      load diets have received little investigation. Therefore, the purpose of this
      research was to examine the food patterns associated with lower-glycemic-load
      diets to establish targeted intervention messages. SUBJECTS/SETTING: A random
      sample (n=179; 81 male and 98 female subjects) of older adults > or =65 years of
      age in the Geisinger Rural Aging study, a nutritional risk screening study.
      METHODS: Standardized methodology was used to calculate the glycemic load from
      data obtained in five 24-hour recalls. Statistical analysis t tests compared
      dietary patterns between male and female subjects from two eating pattern
      clusters identified in previous cluster analysis based on food group intake.
      RESULTS: The mean (+/-standard deviation) glycemic load for the entire sample was
      115.6 (+/-39.9). Two clusters were identified, and male and female subjects in
      one cluster had a lower glycemic load (113.7+/-44.2 and 94.0+/-27.5,
      respectively) than male and female subjects in the second cluster (139.9+/-38.8
      and 110.7+/-35.9, respectively) ( P <.01). Participants in the lower-glycemic
      load cluster consumed more carbohydrate from cereal, fruits, vegetables, and
      milk, whereas those in the higher-glycemic-load cluster consumed more breads and
      desserts. CONCLUSIONS: Promoting appropriate portions of nutrient-dense
      carbohydrate foods, particularly whole grain, fruits, vegetables, and dairy
      foods, may offer reasonable guidance for lowering the glycemic load of the diet
      among older adults. A lower-glycemic-load diet may reduce the risk for obesity
      and many chronic diseases.

PMID- 15565078
TI  - Choline- and betaine-defined diets for use in clinical research and for the
      management of trimethylaminuria.
AB  - This article describes the development of a series of choline- and betaine
      controlled diets that were served to research subjects as part of an ongoing
      study of diet requirements in humans. These diets were developed based on the
      analysis of choline and betaine in individual foods. The calculated diets were
      compared with analyses of all foods combined into a single sample for each day.
      The laboratory analyses of choline and betaine in the whole-diet aliquots matched
      the estimated amounts in the diets that were calculated from the analyses of
      individual foods. These diets were adjusted for several levels of choline and
      betaine and were well accepted by research subjects who consumed them for a time
      period of up to 2 months. This article describes applications of this diet for
      use in clinical research on methyl-group requirements in humans and for use in
      clinical practice for counseling the client who requires a choline-controlled
      diet.

PMID- 15565079
TI  - Research navigating the course of clinical practice in diabetes.
AB  - Three of the four largest and, arguably, most important long-term clinical trials
      focusing on diabetes in the past 2 decades have had medical nutrition therapy
      (MNT) as a major element of their experimental therapies: the Diabetes Control
      and Complications Trial and its follow-up study the Epidemiology of Diabetes
      Interventions and Complications Study, the Diabetes Prevention Program, and the
      Look AHEAD (Action for Health in Diabetes) study. The important features of these
      studies, their major results, and implications for current and future practice of
      MNT in the prevention and treatment of diabetes are delineated. The evidence
      suggests that dietetics professionals have an increasingly important role in the
      early initiation of MNT in the treatment and prevention of diabetes and in
      establishing the long-term relationships required to shape behavior and sustain
      the lifestyle habits that translate into significant reductions in the incidence
      of diabetes-related health outcomes and improved cost-effectiveness over time.

PMID- 15565080
TI  - Postprandial glucose response to Chinese foods in patients with type 2 diabetes.
AB  - The objective of this study is to examine the glycemic response to common Chinese
      foods in patients with type 2 diabetes. Twenty-four Chinese adults with type 2
      diabetes participated. Subjects were allocated to eat a pair of test meals in
      random order. Test meals included plain porridge with lean pork (meal 1A), plain
      porridge and Shrimp Shao Mai (Doll Brand, Winner Food Products Limited, Hong
      Kong) (meal 1B), boiled rice with boiled egg white (meal 2A), fried rice with
      whole egg (meal 2B), plain noodles in clear soup (meal 3A), and Pickled Vegetable
      and Pork-flavored Instant Bowl Noodles (Doll Brand, Winner Food Products Limited)
      (meal 3B). Nutritional content of the meals was calculated from the nutritional
      label on the food package and the food composition table. Plasma glucose was
      checked before the meal and in 30-minute intervals for up to 4 hours after the
      meal. Significant differences in the area under the curve of glucose up to 2
      hours after the meal were detected between meal 1A and 2A ( P =.044), 1A and 3A (
      P =.001), and 3A and 3B ( P =.017). The results suggest that fat alone does not
      alter the glycemic response to rice or porridge. Porridge produces a higher
      glycemic response than rice and noodles despite similar carbohydrate contents,
      and different noodles lead to differences in glycemic excursion, suggesting that
      the glycemic index of common Chinese foods is affected by cooking methods and
      food processing.

PMID- 15565081
TI  - Physical activity minimizes the association of body fatness with abdominal
      obesity in white, premenopausal women: results from the Third National Health and
      Nutrition Examination Survey.
AB  - This study explored the association of physical activity with body fatness and
      abdominal obesity in 1,004 premenopausal white women who participated in the
      Third National Health and Nutrition Examination Survey. Physical activity was
      classified into four levels based on fitness criteria from the American College
      of Sports Medicine. Standard protocols were used for measuring body mass index
      (BMI), percent body fat, and waist-to-hip ratio (WHR). Means for BMI, percent
      body fat, and WHR were calculated for each physical activity level. Analysis of
      variance procedures were performed, followed by pair-wise comparisons, to
      determine differences among means and for trends. Mean BMI, percent body fat, and
      WHR were significantly less ( P < .001) at each higher physical activity level
      except between Levels 0 and 1. The ability of increased daily physical activity
      to minimize age-related increases in abdominal obesity could be a strong
      incentive for women approaching menopause to become more physically active.

PMID- 15565082
TI  - Advice that includes food sources of unsaturated fat supports future risk
      management of gestational diabetes mellitus.
AB  - Abstract Women with gestational diabetes mellitus (GDM) have a greater risk of
      developing type 2 diabetes mellitus (DM) and heart disease than pregnant women
      without GDM. Advice given during the GDM pregnancy provides an opportunity to
      develop protective dietary patterns for the long-term management of this risk.
      Dietary guidelines for the prevention and management of type 2 DM support the
      inclusion of unsaturated fats, but food advice needs to target this outcome. The
      aim of this study was to compare the dietary intakes of women with GDM given
      general low-fat advice (control group) to women with GDM given the same advice
      with additional targets for food sources of unsaturated fats (intervention
      group). After approximately 6 weeks, the intervention group reported more ideal
      dietary fatty acid intakes than the control group, with polyunsaturated:saturated
      fat ratios of 1:1 and 0.4:1, respectively ( P < .001), assessed using repeated
      measures analysis of variance. These results confirm the need to include food
      sources of unsaturated fats in advice strategies to assure optimal protective
      eating habits in this at-risk group.

PMID- 15565083
TI  - Cholesterol-lowering effect of the Food for Heart Nutrition Education Program.
AB  - The objective of this prospective, randomized controlled trial was to assess the
      effectiveness of the Food For Heart Program patient nutrition tool in
      hypercholesterolemic outpatients. The setting for this study was an urban
      academic primary-care practice; 175 hypercholesterolemic adults not taking
      cholesterol-lowering medications were enrolled as subjects. The study
      intervention involved four monthly dietary counseling visits, using the Food For
      Heart Program, conducted by the study research assistant. The main outcome
      measures were fasting serum lipids (primary); body weight (secondary); and change
      in Dietary Risk Assessment score (intervention group only), analyzed using
      Student's t test. Our results showed that total and low-density lipoprotein
      cholesterol decreased 0.40+/-0.65 mmol/L and 0.32+/-0.58 mmol/L, respectively, in
      the intervention group (n=91), compared with 0.06+/-0.57 mmol/L and 0.0088+/-0.56
      mmol/L in the control group (n=84) ( P <.001). There was no significant change in
      high-density lipoprotein cholesterol. Intervention subjects lost a small but
      statistically significant amount of weight, 2.2+/-7.4 pounds ( P <.01), and
      decreased their Dietary Risk Assessment score 5.9+/-6.5 points ( P <.001). Based
      on these findings, we concluded that total and low-density lipoprotein
      cholesterol, weight, and dietary risk for coronary heart disease decreased
      significantly in hypercholesterolemic patients counseled using the Food For Heart
      Program.

PMID- 15565084
TI  - Adherence to the food guide pyramid recommendations among African Americans and
      Latinos: results from the Multiethnic Cohort.
AB  - The objective of the study was to determine the degree of adherence to the Food
      Guide Pyramid recommendations among African Americans, Latinos born in the United
      States, and Latinos born in Mexico. Subjects were from the Multiethnic Cohort
      Study in Hawaii and Los Angeles, and completed a self-administered quantitative
      food frequency questionnaire at baseline in 1993-1996. Dairy recommendations were
      the least likely of all the food group recommendations to be followed, with 61%
      to 99% of individuals in the three ethnic groups not consuming the recommended
      number of servings. African Americans were less likely to adhere to all of the
      food group recommendations compared to the two Latino groups. A greater
      percentage of Latinos born in the United States did not adhere to the food group
      recommendations compared to Latinos born in Mexico. All three groups would
      benefit from interventions designed to promote healthy food choices.

PMID- 15565085
TI  - A standardized nutrition care process and language are essential components of a
      conceptual model to guide and document nutrition care and patient outcomes.
AB  - Documentation of clinical services within health care systems has become
      increasingly significant because greater amounts of information are now required
      by accrediting agencies, third-party payers, researchers, and others in their
      evaluation of patient care and because of the increasing emphasis on patient
      outcomes. Given the multiple users who depend on health care information in the
      patient record, it is imperative that clinical nutrition practitioners implement
      a standardized nutrition care process and language to document comprehensively
      and communicate meaningful information concerning their role in improving patient
      outcomes. A body of work has led to the development and adoption of a
      standardized nutrition care process for the dietetics profession. A standardized
      nutrition care process consistent with the scientific method and a standardized
      language are two essential components required to articulate a conceptual model
      for clinical nutrition practice and documentation and distinguish clinical
      dietetics' unique body of knowledge. The conceptual model serves as an organizing
      framework to standardize and guide nutrition practitioners' clinical judgments or
      critical thinking processes and document information linking nutrition care to
      patient outcomes.

PMID- 15565086
TI  - Serving on the Institute of Medicine's Dietary Reference Intake Panel for
      Electrolytes and Water.

PMID- 15565099
TI  - A treasury of exceptions.

PMID- 15565101
TI  - In genetic control of disease, does 'race' matter?

PMID- 15565102
TI  - Shaping small RNAs in plants by gene duplication.

PMID- 15565103
TI  - Exploring nematode diversity.

PMID- 15565104
TI  - PTPN22 and autoimmune disease.

PMID- 15565107
TI  - Insulin regulation of heart function in aging fruit flies.
AB  - Insulin-IGF receptor (InR) signaling has a conserved role in regulating lifespan,
      but little is known about the genetic control of declining organ function. Here,
      we describe progressive changes of heart function in aging fruit flies: from one
      to seven weeks of a fly's age, the resting heart rate decreases and the rate of
      stress-induced heart failure increases. These age-related changes are minimized
      or absent in long-lived flies when systemic levels of insulin-like peptides are
      reduced and by mutations of the only receptor, InR, or its substrate, chico.
      Moreover, interfering with InR signaling exclusively in the heart, by
      overexpressing the phosphatase dPTEN or the forkhead transcription factor dFOXO,
      prevents the decline in cardiac performance with age. Thus, insulin-IGF signaling
      influences age-dependent organ physiology and senescence directly and
      autonomously, in addition to its systemic effect on lifespan. The aging fly heart
      is a model for studying the genetics of age-sensitive organ-specific pathology.

PMID- 15565108
TI  - Evolution of microRNA genes by inverted duplication of target gene sequences in
      Arabidopsis thaliana.
AB  - MicroRNAs (miRNAs) in plants and animals function as post-transcriptional
      regulators of target genes, many of which are involved in multicellular
      development. miRNAs guide effector complexes to target mRNAs through base-pair
      complementarity, facilitating site-specific cleavage or translational repression.
      Biogenesis of miRNAs involves nucleolytic processing of a precursor transcript
      with extensive foldback structure. Here, we provide evidence that genes encoding
      miRNAs in plants originated by inverted duplication of target gene sequences.
      Several recently evolved genes encoding miRNAs in Arabidopsis thaliana and other
      small RNA-generating loci possess the hallmarks of inverted duplication events
      that formed the arms on each side of their respective foldback precursors. We
      propose a model for miRNA evolution that suggests a mechanism for de novo
      generation of new miRNA genes with unique target specificities.

PMID- 15565109
TI  - Application of comparative functional genomics to identify best-fit mouse models
      to study human cancer.
AB  - Genetically modified mice have been extensively used for analyzing the molecular
      events that occur during tumor development. In many, if not all, cases, however,
      it is uncertain to what extent the mouse models reproduce features observed in
      the corresponding human conditions. This is due largely to lack of precise
      methods for direct and comprehensive comparison at the molecular level of the
      mouse and human tumors. Here we use global gene expression patterns of 68
      hepatocellular carcinomas (HCCs) from seven different mouse models and 91 human
      HCCs from predefined subclasses to obtain direct comparison of the molecular
      features of mouse and human HCCs. Gene expression patterns in HCCs from Myc, E2f1
      and Myc E2f1 transgenic mice were most similar to those of the better survival
      group of human HCCs, whereas the expression patterns in HCCs from Myc Tgfa
      transgenic mice and in diethylnitrosamine-induced mouse HCCs were most similar to
      those of the poorer survival group of human HCCs. Gene expression patterns in
      HCCs from Acox1(-/-) mice and in ciprofibrate-induced HCCs were least similar to
      those observed in human HCCs. We conclude that our approach can effectively
      identify appropriate mouse models to study human cancers.

PMID- 15565110
TI  - Polymorphisms in FKBP5 are associated with increased recurrence of depressive
      episodes and rapid response to antidepressant treatment.
AB  - The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been
      implicated in the causality as well as the treatment of depression. To
      investigate a possible association between genes regulating the HPA axis and
      response to antidepressants and susceptibility for depression, we genotyped
      single-nucleotide polymorphisms in eight of these genes in depressed individuals
      and matched controls. We found significant associations of response to
      antidepressants and the recurrence of depressive episodes with single-nucleotide
      polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp
      90, in two independent samples. These single-nucleotide polymorphisms were also
      associated with increased intracellular FKBP5 protein expression, which triggers
      adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation.
      Individuals carrying the associated genotypes had less HPA-axis hyperactivity
      during the depressive episode. We propose that the FKBP5 variant-dependent
      alterations in HPA-axis regulation could be related to the faster response to
      antidepressant drug treatment and the increased recurrence of depressive episodes
      observed in this subgroup of depressed individuals. These findings support a
      central role of genes regulating the HPA axis in the causality of depression and
      the mechanism of action of antidepressant drugs.

PMID- 15565111
TI  - Google nouveau.

PMID- 15565112
TI  - Conscience call.

PMID- 15565113
TI  - Science searches shift up a gear as Google starts Scholar engine.

PMID- 15565114
TI  - NIH head stands firm over plans for open access.

PMID- 15565115
TI  - Lean budget leaves scientists wanting more.

PMID- 15565116
TI  - Report censures political screening of advisory boards.

PMID- 15565117
TI  - Huge study of children aims to get the dirt on development.

PMID- 15565118
TI  - Summit calls for clear view of deposits in all biobanks.

PMID- 15565119
TI  - Junior scientists are denied access to data, says survey.

PMID- 15565120
TI  - Asian nations build bridges to bolster science.

PMID- 15565121
TI  - Chemistry claim provokes strong reaction.

PMID- 15565123
TI  - Nuclear proliferation special: we have the technology.

PMID- 15565124
TI  - Benveniste's reputation was not written in water.

PMID- 15565125
TI  - Presidential candidates failed peer-review test.

PMID- 15565126
TI  - DDT still has a role in the fight against malaria.

PMID- 15565127
TI  - Replacement therapy, not recreational tonic.

PMID- 15565128
TI  - Revisiting the Baruch Plan.

PMID- 15565132
TI  - Crazy, but correct.

PMID- 15565133
TI  - Human behaviour: don't lose your reputation.

PMID- 15565134
TI  - Materials science: a 'bed of nails' on silicon.

PMID- 15565135
TI  - Regenerative medicine: Prometheus unbound.

PMID- 15565137
TI  - Quantum information: atomic recorder for light quanta.

PMID- 15565138
TI  - Evolutionary biology: light on ancient photoreceptors.

PMID- 15565139
TI  - Nonlinear physics: fresh breather.

PMID- 15565140
TI  - Molecular biology: termination by torpedo.

PMID- 15565142
TI  - Water resources: groundwater maintains dune landscape.
AB  - The Badain Jaran desert in western Inner Mongolia in China has a unique landscape
      that contains 72 lakes, with a total water surface area of 23 km2, and the
      world's highest stationary sand dunes, which are up to 500 m tall--despite the
      prevailing dry and windy weather conditions. Here we present evidence of a major
      groundwater system that underpins the factors leading to this landscape. Our
      finding could transform plans for the region's water resources.

PMID- 15565143
TI  - Palaeoclimate: ocean tides and Heinrich events.
AB  - Climate varied enormously over the most recent ice age--for example, large pulses
      of ice-rafted debris, originating mainly from the Labrador Sea, were deposited
      into the North Atlantic at roughly 7,000-year intervals, with global climatic
      implications. Here we show that ocean tides within the Labrador Sea were
      exceptionally large over the period spanning these huge, abrupt ice movements,
      which are known as Heinrich events. We propose that tides played a catalytic role
      in liberating iceberg armadas during that time.

PMID- 15565144
TI  - Neanderthals and the modern human colonization of Europe.
AB  - The fate of the Neanderthal populations of Europe and western Asia has gripped
      the popular and scientific imaginations for the past century. Following at least
      200,000 years of successful adaptation to the glacial climates of northwestern
      Eurasia, they disappeared abruptly between 30,000 and 40,000 years ago, to be
      replaced by populations all but identical to modern humans. Recent research
      suggests that the roots of this dramatic population replacement can be traced far
      back to events on another continent, with the appearance of distinctively modern
      human remains and artefacts in eastern and southern Africa.

PMID- 15565145
TI  - Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell
      migration, survival and cardiac repair.
AB  - Heart disease is a leading cause of death in newborn children and in adults.
      Efforts to promote cardiac repair through the use of stem cells hold promise but
      typically involve isolation and introduction of progenitor cells. Here, we show
      that the G-actin sequestering peptide thymosin beta4 promotes myocardial and
      endothelial cell migration in the embryonic heart and retains this property in
      postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in
      culture was also enhanced by thymosin beta4. We found that thymosin beta4 formed
      a functional complex with PINCH and integrin-linked kinase (ILK), resulting in
      activation of the survival kinase Akt (also known as protein kinase B). After
      coronary artery ligation in mice, thymosin beta4 treatment resulted in
      upregulation of ILK and Akt activity in the heart, enhanced early myocyte
      survival and improved cardiac function. These findings suggest that thymosin
      beta4 promotes cardiomyocyte migration, survival and repair and the pathway it
      regulates may be a new therapeutic target in the setting of acute myocardial
      damage.

PMID- 15565146
TI  - Human DNA ligase I completely encircles and partially unwinds nicked DNA.
AB  - The end-joining reaction catalysed by DNA ligases is required by all organisms
      and serves as the ultimate step of DNA replication, repair and recombination
      processes. One of three well characterized mammalian DNA ligases, DNA ligase I,
      joins Okazaki fragments during DNA replication. Here we report the crystal
      structure of human DNA ligase I (residues 233 to 919) in complex with a nicked,
      5' adenylated DNA intermediate. The structure shows that the enzyme redirects the
      path of the double helix to expose the nick termini for the strand-joining
      reaction. It also reveals a unique feature of mammalian ligases: a DNA-binding
      domain that allows ligase I to encircle its DNA substrate, stabilizes the DNA in
      a distorted structure, and positions the catalytic core on the nick. Similarities
      in the toroidal shape and dimensions of DNA ligase I and the proliferating cell
      nuclear antigen sliding clamp are suggestive of an extensive protein-protein
      interface that may coordinate the joining of Okazaki fragments.

PMID- 15565147
TI  - The building blocks of planets within the 'terrestrial' region of protoplanetary
      disks.
AB  - Our Solar System was formed from a cloud of gas and dust. Most of the dust mass
      is contained in amorphous silicates, yet crystalline silicates are abundant
      throughout the Solar System, reflecting the thermal and chemical alteration of
      solids during planet formation. (Even primitive bodies such as comets contain
      crystalline silicates.) Little is known about the evolution of the dust that
      forms Earth-like planets. Here we report spatially resolved detections and
      compositional analyses of these building blocks in the innermost two astronomical
      units of three proto-planetary disks. We find the dust in these regions to be
      highly crystallized, more so than any other dust observed in young stars until
      now. In addition, the outer region of one star has equal amounts of pyroxene and
      olivine, whereas the inner regions are dominated by olivine. The spectral shape
      of the inner-disk spectra shows surprising similarity with Solar System comets.
      Radial-mixing models naturally explain this resemblance as well as the gradient
      in chemical composition. Our observations imply that silicates crystallize before
      any terrestrial planets are formed, consistent with the composition of meteorites
      in the Solar System.

PMID- 15565148
TI  - Experimental demonstration of quantum memory for light.
AB  - The information carrier of today's communications, a weak pulse of light, is an
      intrinsically quantum object. As a consequence, complete information about the
      pulse cannot be perfectly recorded in a classical memory, even in principle. In
      the field of quantum information, this has led to the long-standing challenge of
      how to achieve a high-fidelity transfer of an independently prepared quantum
      state of light onto an atomic quantum state. Here we propose and experimentally
      demonstrate a protocol for such a quantum memory based on atomic ensembles.
      Recording of an externally provided quantum state of light onto the atomic
      quantum memory is achieved with 70 per cent fidelity, significantly higher than
      the limit for classical recording. Quantum storage of light is achieved in three
      steps: first, interaction of the input pulse and an entangling field with spin
      polarized caesium atoms; second, subsequent measurement of the transmitted light;
      and third, feedback onto the atoms using a radio-frequency magnetic pulse
      conditioned on the measurement result. The density of recorded states is 33 per
      cent higher than the best classical recording of light onto atoms, with a quantum
      memory lifetime of up to 4 milliseconds.

PMID- 15565149
TI  - Direct observation of the discrete character of intrinsic localized modes in an
      antiferromagnet.
AB  - In a strongly nonlinear discrete system, the spatial size of an excitation can
      become comparable to, and influenced by, the lattice spacing. Such intrinsic
      localized modes (ILMs)--also called 'discrete breathers' or 'lattice solitons'-
      are responsible for energy localization in the dynamics of discrete nonlinear
      lattices. Their energy profiles resemble those of localized modes of defects in a
      harmonic lattice but, like solitons, they can move (although, unlike solitons,
      some energy is exchanged during collisions between them). The manipulation of
      these localized energy 'hotspots' has been achieved in systems as diverse as
      annular arrays of coupled Josephson junctions, optical waveguide arrays, two
      dimensional nonlinear photonic crystals and micromechanical cantilever arrays.
      There is also some evidence for the existence of localized excitations in atomic
      lattices, although individual ILMs have yet to be identified. Here we report the
      observation of countable localized excitations in an antiferromagnetic spin
      lattice by means of a nonlinear spectroscopic technique. This detection
      capability permits the properties of individual ILMs to be probed; the
      disappearance of each ILM registers as a step in the time-dependent signal, with
      the surprising result that the energy staircase of ILM excitations is uniquely
      defined.

PMID- 15565150
TI  - Room-temperature fabrication of transparent flexible thin-film transistors using
      amorphous oxide semiconductors.
AB  - Transparent electronic devices formed on flexible substrates are expected to meet
      emerging technological demands where silicon-based electronics cannot provide a
      solution. Examples of active flexible applications include paper displays and
      wearable computers. So far, mainly flexible devices based on hydrogenated
      amorphous silicon (a-Si:H) and organic semiconductors have been investigated.
      However, the performance of these devices has been insufficient for use as
      transistors in practical computers and current-driven organic light-emitting
      diode displays. Fabricating high-performance devices is challenging, owing to a
      trade-off between processing temperature and device performance. Here, we propose
      to solve this problem by using a novel semiconducting material--namely, a
      transparent amorphous oxide semiconductor from the In-Ga-Zn-O system (a-IGZO)-
      for the active channel in transparent thin-film transistors (TTFTs). The a-IGZO
      is deposited on polyethylene terephthalate at room temperature and exhibits Hall
      effect mobilities exceeding 10 cm2 V(-1) s(-1), which is an order of magnitude
      larger than for hydrogenated amorphous silicon. TTFTs fabricated on polyethylene
      terephthalate sheets exhibit saturation mobilities of 6-9 cm2 V(-1) s(-1), and
      device characteristics are stable during repetitive bending of the TTFT sheet.

PMID- 15565151
TI  - Equilibrium cluster formation in concentrated protein solutions and colloids.
AB  - Controlling interparticle interactions, aggregation and cluster formation is of
      central importance in a number of areas, ranging from cluster formation in
      various disease processes to protein crystallography and the production of
      photonic crystals. Recent developments in the description of the interaction of
      colloidal particles with short-range attractive potentials have led to
      interesting findings including metastable liquid-liquid phase separation and the
      formation of dynamically arrested states (such as the existence of attractive and
      repulsive glasses, and transient gels). The emerging glass paradigm has been
      successfully applied to complex soft-matter systems, such as colloid-polymer
      systems and concentrated protein solutions. However, intriguing problems like the
      frequent occurrence of cluster phases remain. Here we report small-angle
      scattering and confocal microscopy investigations of two model systems: protein
      solutions and colloid-polymer mixtures. We demonstrate that in both systems, a
      combination of short-range attraction and long-range repulsion results in the
      formation of small equilibrium clusters. We discuss the relevance of this finding
      for nucleation processes during protein crystallization, protein or DNA self
      assembly and the previously observed formation of cluster and gel phases in
      colloidal suspensions.

PMID- 15565152
TI  - A humid climate state during the Palaeocene/Eocene thermal maximum.
AB  - An abrupt climate warming of 5 to 10 degrees C during the Palaeocene/Eocene
      boundary thermal maximum (PETM) 55 Myr ago is linked to the catastrophic release
      of approximately 1,050-2,100 Gt of carbon from sea-floor methane hydrate
      reservoirs. Although atmospheric methane, and the carbon dioxide derived from its
      oxidation, probably contributed to PETM warming, neither the magnitude nor the
      timing of the climate change is consistent with direct greenhouse forcing by the
      carbon derived from methane hydrate. Here we demonstrate significant differences
      between marine and terrestrial carbon isotope records spanning the PETM. We use
      models of key carbon cycle processes to identify the cause of these differences.
      Our results provide evidence for a previously unrecognized discrete shift in the
      state of the climate system during the PETM, characterized by large increases in
      mid-latitude tropospheric humidity and enhanced cycling of carbon through
      terrestrial ecosystems. A more humid atmosphere helps to explain PETM
      temperatures, but the ultimate mechanisms underlying the shift remain unknown.

PMID- 15565153
TI  - Indirect reciprocity can stabilize cooperation without the second-order free
      rider problem.
AB  - Models of large-scale human cooperation take two forms. 'Indirect reciprocity'
      occurs when individuals help others in order to uphold a reputation and so be
      included in future cooperation. In 'collective action', individuals engage in
      costly behaviour that benefits the group as a whole. Although the evolution of
      indirect reciprocity is theoretically plausible, there is no consensus about how
      collective action evolves. Evidence suggests that punishing free riders can
      maintain cooperation, but why individuals should engage in costly punishment is
      unclear. Solutions to this 'second-order free rider problem' include meta
      punishment, mutation, conformism, signalling and group-selection. The threat of
      exclusion from indirect reciprocity can sustain collective action in the
      laboratory. Here, we show that such exclusion is evolutionarily stable, providing
      an incentive to engage in costly cooperation, while avoiding the second-order
      free rider problem because punishers can withhold help from free riders without
      damaging their reputations. However, we also show that such a strategy cannot
      invade a population in which indirect reciprocity is not linked to collective
      action, thus leaving unexplained how collective action arises.

PMID- 15565154
TI  - Physical performance and Darwinian fitness in lizards.
AB  - Strong evidence for a genetic basis of variation in physical performance has
      accumulated. Considering one of the basic tenets of evolutionary physiology--that
      physical performance and darwinian fitness are tightly linked--one may expect
      phenotypes with exceptional physiological capacities to be promoted by natural
      selection. Why then does physical performance remain considerably variable in
      human and other animal populations? Our analysis of locomotor performance in the
      common lizard (Lacerta vivipara) demonstrates that initial endurance (running
      time to exhaustion measured at birth) is indeed highly heritable, but natural
      selection in favour of this trait can be unexpectedly weak. A manipulation of
      dietary conditions unravels a proximate mechanism explaining this pattern. Fully
      fed individuals experience a marked reversal of performance within only one month
      after birth: juveniles with low endurance catch up, whereas individuals with high
      endurance lose their advantage. In contrast, dietary restriction allows highly
      endurant neonates to retain their locomotor superiority as they age. Thus, the
      expression of a genetic predisposition to high physical performance strongly
      depends on the environment experienced early in life.

PMID- 15565155
TI  - Predator-induced behaviour shifts and natural selection in field-experimental
      lizard populations.
AB  - The role of behaviour in evolutionary change has long been debated. On the one
      hand, behavioural changes may expose individuals to new selective pressures by
      altering the way that organisms interact with the environment, thus driving
      evolutionary divergence. Alternatively, behaviour can act to retard evolutionary
      change: by altering behavioural patterns in the face of new environmental
      conditions, organisms can minimize exposure to new selective pressures. This
      constraining influence of behaviour has been put forward as an explanation for
      evolutionary stasis within lineages and niche conservatism within clades.
      Nonetheless, the hypothesis that behavioural change prevents natural selection
      from operating in new environments has never been experimentally tested. We
      conducted a controlled and replicated experimental study of selection in entirely
      natural populations; we demonstrate that lizards alter their habitat use in the
      presence of an introduced predator, but that these behavioural shifts do not
      prevent patterns of natural selection from changing in experimental populations.

PMID- 15565156
TI  - Magnetoreception and its trigeminal mediation in the homing pigeon.
AB  - Two conflicting hypotheses compete to explain how a homing pigeon can return to
      its loft over great distances. One proposes the use of atmospheric odours and the
      other the Earth's magnetic field in the 'map' step of the 'map and compass'
      hypothesis of pigeon homing. Although magnetic effects on pigeon orientation
      provide indirect evidence for a magnetic 'map', numerous conditioning experiments
      have failed to demonstrate reproducible responses to magnetic fields by pigeons.
      This has led to suggestions that homing pigeons and other birds have no useful
      sensitivity to the Earth's magnetic field. Here we demonstrate that homing
      pigeons (Columba livia) can discriminate between the presence and absence of a
      magnetic anomaly in a conditioned choice experiment. This discrimination is
      impaired by attachment of a magnet to the cere, local anaesthesia of the upper
      beak area, and bilateral section of the ophthalmic branch of the trigeminal
      nerve, but not of the olfactory nerve. These results suggest that
      magnetoreception (probably magnetite-based) occurs in the upper beak area of the
      pigeon. Traditional methods of rendering pigeons anosmic might therefore cause
      simultaneous impairment of magnetoreception so that future orientation
      experiments will require independent evaluation of the pigeon's magnetic and
      olfactory systems.

PMID- 15565157
TI  - The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase
      II.
AB  - The carboxy-terminal domain (CTD) of the RNA polymerase II (RNApII) largest
      subunit consists of multiple heptapeptide repeats with the consensus sequence
      YSPTSPS. Different CTD phosphorylation patterns act as recognition sites for the
      binding of various messenger RNA processing factors, thereby coupling
      transcription and mRNA processing. Polyadenylation factors are co
      transcriptionally recruited by phosphorylation of CTD serine 2 (ref. 2) and these
      factors are also required for transcription termination. RNApII transcribes past
      the poly(A) site, the RNA is cleaved by the polyadenylation machinery, and the
      RNA downstream of the cleavage site is degraded. Here we show that Rtt103 and the
      Rat1/Rai1 5' --> 3' exonuclease are localized at 3' ends of protein coding genes.
      In rat1-1 or rai1Delta cells, RNA 3' to polyadenylation sites is greatly
      stabilized and termination defects are seen at many genes. These findings support
      a model in which poly(A) site cleavage and subsequent degradation of the 3'
      downstream RNA by Rat1 trigger transcription termination.

PMID- 15565158
TI  - Human 5' --> 3' exonuclease Xrn2 promotes transcription termination at co
      transcriptional cleavage sites.
AB  - Eukaryotic protein-encoding genes possess poly(A) signals that define the end of
      the messenger RNA and mediate downstream transcriptional termination by RNA
      polymerase II (Pol II). Termination could occur through an 'anti-termination'
      mechanism whereby elongation factors dissociate when the poly(A) signal is
      encountered, producing termination-competent Pol II. An alternative 'torpedo'
      model postulated that poly(A) site cleavage provides an unprotected RNA 5' end
      that is degraded by 5' --> 3' exonuclease activities (torpedoes) and so induces
      dissociation of Pol II from the DNA template. This model has been questioned
      because unprocessed transcripts read all the way to the site of transcriptional
      termination before upstream polyadenylation. However, nascent transcripts located
      1 kilobase downstream of the human beta-globin gene poly(A) signal are associated
      with a co-transcriptional cleavage (CoTC) activity that acts with the poly(A)
      signal to elicit efficient transcriptional termination. The CoTC sequence is an
      autocatalytic RNA structure that undergoes rapid self-cleavage. Here we show that
      CoTC acts as a precursor to termination by presenting a free RNA 5' end that is
      recognized by the human 5' --> 3' exonuclease Xrn2. Degradation of the downstream
      cleavage product by Xrn2 results in transcriptional termination, as envisaged in
      the torpedo model.

PMID- 15565159
TI  - Autocatalytic RNA cleavage in the human beta-globin pre-mRNA promotes
      transcription termination.
AB  - New evidence indicates that termination of transcription is an important
      regulatory step, closely related to transcriptional interference and even
      transcriptional initiation. However, how this occurs is poorly understood.
      Recently, in vivo analysis of transcriptional termination for the human beta
      globin gene revealed a new phenomenon--co-transcriptional cleavage (CoTC). This
      primary cleavage event within beta-globin pre-messenger RNA, downstream of the
      poly(A) site, is critical for efficient transcriptional termination by RNA
      polymerase II. Here we show that the CoTC process in the human beta-globin gene
      involves an RNA self-cleaving activity. We characterize the autocatalytic core of
      the CoTC ribozyme and show its functional role in efficient termination in vivo.
      The identified core CoTC is highly conserved in the 3' flanking regions of other
      primate beta-globin genes. Functionally, it resembles the 3' processive, self
      cleaving ribozymes described for the protein-encoding genes from the myxomycetes
      Didymium iridis and Physarum polycephalum, indicating evolutionary conservation
      of this molecular process. We predict that regulated autocatalytic cleavage
      elements within pre-mRNAs may be a general phenomenon and that functionally it
      may provide the entry point for exonucleases involved in mRNA maturation,
      turnover and, in particular, transcriptional termination.

PMID- 15565161
TI  - Material gains.

PMID- 15565162
TI  - Novel dextran-spermine conjugates as transfecting agents: comparing water-soluble
      and micellar polymers.
AB  - Recently, a novel cationic polymer, dextran-spermine (D-SPM) was developed for
      gene delivery. An efficient transfection was obtained using this polycation for a
      variety of genes and cell lines in serum-free or serum-poor medium. However,
      transfection using the water-soluble D-SPM-based polyplexes decreased with
      increasing serum concentration in cell culture in a concentration-dependent
      manner, reaching 95% inhibition at 50% serum in the cell growth medium. In order
      to overcome this obstacle, oleyl derivatives of D-SPM (which form micelles in
      aqueous phase) were synthesized at 1, 10, and 20 mol% of oleyl moiety to polymer
      epsilon-NH2 to form N-oleyl-D-SPM (ODS). Polyplexes based on ODS transfected well
      in medium containing 50% serum. Comparison with polyplexes based on well
      established polymers (branched and linear polyethyleneimine) and with
      DOTAP/Cholesterol lipoplexes showed that regarding beta-galactosidase transgene
      expression level and cytotoxicity in tissue culture, the D-SPM and ODS compare
      well with the above polyplexes and lipoplexes. Intracellular trafficking using
      FITC-labeled ODS and Rhodamine-labeled pGeneGrip plasmid cloned with hBMP2
      monitored by confocal microscopy revealed that during the transfection process
      the fluorescent-labeled polymer concentrates in the Golgi apparatus and around
      the nucleus, while the cell cytoplasm was free of fluorescent particles,
      suggesting that the polyplexes move in the cell toward the nucleus by vesicular
      transport through the cytoplasm and not by a random diffusion. We found that the
      plasmids penetrate the cell nucleus without the polymer. Preliminary results in
      zebra fish and mice demonstrate the potential of ODS to serve as an efficient
      nonviral vector for in vivo transfection.

PMID- 15565163
TI  - All common p210 and p190 Bcr-abl variants can be targeted by RNA interference.

PMID- 15565164
TI  - Outcome of acute promyelocytic leukemia treated with all trans retinoic acid and
      chemotherapy in elderly patients: the European group experience.
AB  - We analyzed the outcome of patients aged more than 60 included in a multicenter
      trial in newly diagnosed acute promyelocytic leukemia (APL93 trial), which tested
      the role of early addition of chemotherapy to all trans retinoic acid (ATRA) and
      of maintenance with ATRA and/or low-dose chemotherapy. In total, 129/533 (24.2%)
      patients included in this trial were older than 60. The CR rate was 86% in
      patients older than 60 as compared to 94.5% in younger patients (P=0.0014), due
      to a higher incidence of early deaths in elderly patients. The 4-year incidence
      of relapse was 15.6% in adults older than 60 and 23.2% in younger adults although
      most elderly patients received less intensive consolidation chemotherapy.
      However, 18.6% of the patients older than 60 years who achieved CR died in CR,
      mainly from sepsis during consolidation course or maintenance treatment, as
      compared to 5.7% of younger adults (P<0.001). Thus, overall 4-year survival of
      elderly patients was 57.8% as compared to 78% in younger adults (P<0.0001). APL
      in elderly patients appears as sensitive to ATRA-Chemotherapy based regimen as in
      younger adults. Less favorable outcome is mainly due to an increase of early
      deaths and to toxicity of consolidation treatment, strongly suggesting a
      beneficial role for less intensive consolidation chemotherapy and possibly
      introduction of arsenic derivates in the treatment of APL in the elderly.

PMID- 15565165
TI  - e6-a2 BCR-ABL1 fusion in T-cell acute lymphoblastic leukemia.

PMID- 15565166
TI  - Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with
      downregulation of CD23 and inactivation of Notch2.
AB  - Recently, proteasome inhibitors (PI) have attracted interest as novel anticancer
      agents in B-cell chronic lymphocytic leukemia (B-CLL). A prominent feature of B
      CLL cells is the high expression of CD23, which is closely related to cell
      survival and is regulated by Notch2. Since several components of the Notch
      signaling cascade are tightly regulated by proteasomal degradation, we studied
      the effect of PI on Notch2 activity and CD23 expression. Exposure of B-CLL cells
      to PI led to induction of apoptosis, a time- and dose-dependent downregulation of
      CD23 expression and a decline in DNA binding of transcriptionally active Notch2.
      In contrast, the transcription factor NF-AT and its putative target gene CD5,
      which is highly expressed in B-CLL cells, were unaffected. When the late phase of
      PI-induced apoptosis was arrested by inhibition of caspase 3, the reduction of
      Notch2 activity was still observed, indicating that reduction of active Notch2
      took place already during an earlier phase of apoptosis. Enforced expression of
      constitutively active Notch2 decreased PI-mediated apoptosis in a human B-cell
      line. These data indicate that downregulation of CD23 and loss of Notch2 activity
      are early steps in PI-induced apoptosis of B-CLL lymphocytes and may be part of
      the full apoptotic response.

PMID- 15565167
TI  - Predicting survival for myeloid leukemia after HLA-identical sibling donor
      allogeneic stem cell transplantation.

PMID- 15565168
TI  - Recognition and cleavage of primary microRNA precursors by the nuclear processing
      enzyme Drosha.
AB  - A critical step during human microRNA maturation is the processing of the primary
      microRNA transcript by the nuclear RNaseIII enzyme Drosha to generate the
      approximately 60-nucleotide precursor microRNA hairpin. How Drosha recognizes
      primary RNA substrates and selects its cleavage sites has remained a mystery,
      especially given that the known targets for Drosha processing show no discernable
      sequence homology. Here, we show that human Drosha selectively cleaves RNA
      hairpins bearing a large (>/=10 nucleotides) terminal loop. From the junction of
      the loop and the adjacent stem, Drosha then cleaves approximately two helical RNA
      turns into the stem to produce the precursor microRNA. Beyond the precursor
      microRNA cleavage sites, approximately one helix turn of stem extension is also
      essential for efficient processing. While the sites of Drosha cleavage are
      determined largely by the distance from the terminal loop, variations in stem
      structure and sequence around the cleavage site can fine-tune the actual cleavage
      sites chosen.

PMID- 15565169
TI  - Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and
      slicer activity.
AB  - RNA silencing regulates gene expression through mRNA degradation, translation
      repression and chromatin remodelling. The fundamental engines of RNA silencing
      are RISC and RITS complexes, whose common components are 21-25 nt RNA and an
      Argonaute protein containing a PIWI domain of unknown function. The crystal
      structure of an archaeal Piwi protein (AfPiwi) is organised into two domains, one
      resembling the sugar-binding portion of the lac repressor and another with
      similarity to RNase H. Invariant residues and a coordinated metal ion lie in a
      pocket that surrounds the conserved C-terminus of the protein, defining a key
      functional region in the PIWI domain. Furthermore, two Asp residues, conserved in
      the majority of Argonaute sequences, align spatially with the catalytic Asp
      residues of RNase H-like catalytic sites, suggesting that in eukaryotic Argonaute
      proteins the RNase H-like domain may possess nuclease activity. The conserved
      region around the C-terminus of the PIWI domain, which is required for small
      interfering RNA (siRNA) binding to AfPiwi, may function as the receptor site for
      the obligatory 5' phosphate of siRNAs, thereby specifying the cleavage position
      of the target mRNA.

PMID- 15565170
TI  - UvrD helicase, unlike Rep helicase, dismantles RecA nucleoprotein filaments in
      Escherichia coli.
AB  - The roles of UvrD and Rep DNA helicases of Escherichia coli are not yet fully
      understood. In particular, the reason for rep uvrD double mutant lethality
      remains obscure. We reported earlier that mutations in recF, recO or recR genes
      suppress the lethality of uvrD rep, and proposed that an essential activity
      common to UvrD and Rep is either to participate in the removal of toxic
      recombination intermediates or to favour the proper progression of replication.
      Here, we show that UvrD, but not Rep, directly prevents homologous recombination
      in vivo. In addition to RecFOR, we provide evidence that RecA contributes to
      toxicity in the rep uvrD mutant. In vitro, UvrD dismantles the RecA nucleoprotein
      filament, while Rep has only a marginal activity. We conclude that UvrD and Rep
      do not share a common activity that is essential in vivo: while Rep appears to
      act at the replication stage, UvrD plays a role of RecA nucleoprotein filament
      remover. This activity of UvrD is similar to that of the yeast Srs2 helicase.

PMID- 15565171
TI  - Molecular mechanism of voltage sensor movements in a potassium channel.
AB  - Voltage-gated potassium channels are six-transmembrane (S1-S6) proteins that form
      a central pore domain (4 x S5-S6) surrounded by four voltage sensor domains (S1
      S4), which detect changes in membrane voltage and control pore opening. Upon
      depolarization, the S4 segments move outward carrying charged residues across the
      membrane field, thereby leading to the opening of the pore. The mechanism of S4
      motion is controversial. We have investigated how S4 moves relative to the pore
      domain in the prototypical Shaker potassium channel. We introduced pairs of
      cysteines, one in S4 and the other in S5, and examined proximity changes between
      each pair of cysteines during activation, using Cd2+ and copper-phenanthroline,
      which crosslink the cysteines with metal and disulphide bridges, respectively.
      Modelling of the results suggests a novel mechanism: in the resting state, the
      top of the S3b-S4 voltage sensor paddle lies close to the top of S5 of the
      adjacent subunit, but moves towards the top of S5 of its own subunit during
      depolarization--this motion is accompanied by a reorientation of S4 charges to
      the extracellular phase.

PMID- 15565172
TI  - Proteomic analysis identifies a new complex required for nuclear pre-mRNA
      retention and splicing.
AB  - Using the proteomic tandem affinity purification (TAP) method, we have purified
      the Saccharomyces cerevisie U2 snRNP-associated splicing factors SF3a and SF3b.
      While SF3a purification revealed only the expected subunits Prp9p, Prp11p and
      Prp21p, yeast SF3b was found to contain only six subunits, including previously
      known components (Rse1p, Hsh155p, Cus1p, Hsh49p), the recently identified Rds3p
      factor and a new small essential protein (Ysf3p) encoded by an unpredicted split
      ORF in the yeast genome. Surprisingly, Snu17p, the proposed yeast orthologue of
      the seventh human SF3b subunit, p14, was not found in the yeast complex. TAP
      purification revealed that Snu17p, together with Bud13p and a newly identified
      factor, Pml1p/Ylr016c, form a novel trimeric complex. Subunits of this complex
      were not essential for viability. However, they are required for efficient
      splicing in vitro and in vivo. Furthermore, inactivation of this complex causes
      pre-mRNA leakage from the nucleus. The corresponding complex was named pre-mRNA
      REtention and Splicing (RES). The presence of RES subunit homologues in numerous
      eukaryotes suggests that its function is evolutionarily conserved.

PMID- 15565173
TI  - The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo
      responsiveness in leukocytes.
AB  - Toll-like receptor 4 (TLR-4) is required for detection of Gram negative bacterial
      infections by binding lipopolysaccharide (LPS) and for the initiation of
      inflammatory signaling. Recent studies have demonstrated that a nonsynonymous
      single-nucleotide polymorphism (Asp299Gly, A+896G) is associated with decreased
      endotoxin responsiveness and poor outcomes from sepsis. We show that human
      carriers of this polymorphism show no deficit in LPS induced peripheral blood
      mononuclear cell (PBMC) mitogen-activated protein kinase (MAPK) activity, no
      reduction in sensitivity to endotoxin, and variable differences in whole-blood
      inflammatory cytokine production. These results indicate that this mutation is
      not a primary determinant of human endotoxin sensitivity.

PMID- 15565174
TI  - Evaluation of the A&D UA-767 and Welch Allyn Spot Vital Signs noninvasive blood
      pressure monitors using a blood pressure simulator.
AB  - The performance of five units of the A&D UA-767 NIBP monitor and five units of
      the Welch Allyn Spot Vital Signs noninvasive blood pressure monitor was evaluated
      with the Biotek BP Pump blood pressure simulator under a variety of conditions.
      Using the simulator to provide a normal blood pressure waveform at 80 bpm over a
      range of pressures, it was found that the mean bias for the combined results from
      the A&D monitors was 1.9+/-2.8 mmHg and from the Welch Allyn monitors was 0.7+/
      2.4 mmHg. No individual measurement showed a bias greater than 10 mmHg. A bias of
      greater than 5 mmHg was present in 28 out of 150 measurements for the A&D monitor
      and 10 out of 150 measurements for the Welch Allyn monitor. These results are
      comparable with ratings achieved by the instruments when tested previously
      according to the British Hypertension Society protocol, but testing with a
      simulator allowed assessment of aspects of performance which were not included in
      the British Hypertension Society protocol.

PMID- 15565175
TI  - Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt
      sensitivity and cardiovascular risk factors in Hispanics.
AB  - Mutations in the endothelial nitric oxide synthase (eNOS) gene may be associated
      with abnormal nitric oxide (NO) production and cardiovascular diseases. In this
      study, we investigated the prevalence of two eNOS polymorphisms, the Glu298Asp
      variant on exon 7, and the 4a/b variable number of tandem repeats (VNTR) on
      intron 4, and their association with blood pressure (BP), NO production, salt
      sensitivity and cardiovascular risk factors in healthy Venezuelans. The
      prevalence of both polymorphisms in Venezuelans was comparable to that described
      for Caucasians, but significantly different from that known for African-Americans
      and Japanese. The 4a/b genotype was associated with reduced levels of NO
      metabolites (25% decrease), larger BP lowering in response to salt restriction
      (9.0 vs 4.8 mmHg, P<0.05), greater prevalence of salt sensitivity (39% in 4a/b
      and 27% in 4b/b; P<0.05) and with higher LDL-cholesterol levels. The Glu298T
      polymorphism did not affect NO production, nor it was associated with salt
      sensitivity. Glu298Asp polymorphism was positively associated with higher weight,
      triglycerides and LDL-cholesterol. Neither polymorphism was associated with
      changes in fasting or postload serum glucose, BP, obesity and albuminuria. In
      conclusion, the prevalence of eNOS polymorphisms is strongly determined by ethnic
      factors. The 4a/b gene polymorphism could be a genetic susceptibility factor for
      the BP response to salt intake and for the genetic control of NO production. The
      reduced NO production in subjects with the 4a/b genotype may be responsible for
      the increased sensitivity of their BP to salt.

PMID- 15565176
TI  - Resistant hypertension in patients with chronic aortic dissection.
AB  - Strict blood pressure control is pivotal in the management of patients with
      aortic dissection (AD), but is frequently difficult to achieve. We determined
      antihypertensive medical therapy and levels of blood pressure (BP) control in 40
      patients with chronic AD. Patient charts were reviewed for clinical variables,
      serial BP measurements, and antihypertensive drug therapy. Patients were divided
      into two groups: patients in group 1 had effective BP control (<135/80 mmHg),
      patients in group 2 had resistant hypertension (BP>/=135/80 mmHg despite
      prescription of at least three antihypertensive drugs). Overall, systolic BP
      (SBP) was 130+/-20 mmHg, and diastolic BP (DBP) was 72+/-13 mmHg. Patients
      received a median of 4 (1-6) antihypertensive drugs. beta-blockers were used in
      38/40 (95%) patients. Effective BP control was achieved in 24/40 (60%) patients
      (group 1), while 16/40 (40%) patients had resistant hypertension (group 2)
      despite receiving significantly more antihypertensive drugs (5 [4-6] vs 4 [1-5],
      P=0.001). Mean SBP was 116+/-9 (101-132) mmHg in group 1 and 151+/-13 (137-181)
      mmHg in group 2 (P<0.001); there was no difference in DBP. Group 2 patients had a
      significantly higher body mass index and were younger than patients in group 1.
      In conclusion, in the majority of patients with chronic AD, effective BP control
      can be achieved, but usually requires the combination of multiple
      antihypertensive drugs. However, in a significant proportion of patients (40%),
      who appear to be younger and more obese, medical therapy fails to achieve
      effective BP control despite use of a multiple drug regimen.

PMID- 15565177
TI  - A novel mitochondrial protein DIP mediates E2F1-induced apoptosis independently
      of p53.
AB  - The transcription factor E2F1 does not only induce cell proliferation but also
      shows the strongest proapoptotic effect of all E2F family members as part of an
      antitumor safeguard mechanism. We have recently identified KIAA0767 as a novel
      p53-independent target of E2F1. Here, we investigated the biological function of
      interaction. Overexpression studies of KIAA0767, termed D(eath)-I(nducing)
      P(rotein), revealed its strong proapoptotic effect. DIP greatly reduced cell
      viability in several in vitro systems accompanied by typical apoptotic features
      such as caspase-3 activation and cleavage of poly(ADP-ribose)-polymerase.
      Endogenous DIP levels increased following E2F1 activation. Yet, inhibition of
      endogenous DIP function by small interfering RNA rescued p53-negative cells from
      E2F1-induced apoptosis, indicating that DIP is an essential mediator of the p53
      independent E2F1 death pathway. Localization studies showed that DIP localizes to
      the mitochondria, where endogenous DIP is upregulated following E2F1 induction.
      These results provide new insights to the incompletely understood regulatory
      mechanisms of E2F1-induced apoptosis.

PMID- 15565178
TI  - Atrial natriuretic peptide induces cell death in human hepatoblastoma (HepG2)
      through the involvement of NADPH oxidase.

PMID- 15565179
TI  - Systemic therapy of experimental breast cancer metastases by mutant vesicular
      stomatitis virus in immune-competent mice.
AB  - In view of the limited success of available treatment modalities for metastatic
      breast cancer, alternative and complementary strategies need to be developed.
      Oncolytic vesicular stomatitis virus (VSV) is a promising novel therapeutic agent
      for the treatment of cancer. The aim of this study was to evaluate the potential
      of recombinant VSV containing the M51R mutation in the matrix (M) protein gene
      administered intravenously as an effective and safe therapeutic agent for
      treating mice with experimental breast cancer metastases. Recombinant VSV(M51R)
      LacZ was generated and characterized in vitro on human and murine breast cancer
      cells. Breast cancer metastases were established in immune-competent Balb/c mice
      by intravenous injection of syngeneic 4T1 cells. The vector was infused into the
      tumor-bearing animals via the tail vein, and productive infection of pulmonary
      breast cancer lesions was assessed by X-gal stainings of frozen lung sections. To
      evaluate potential systemic toxicity, histology of major organs and serum
      chemistries were analyzed. To assess effectiveness, buffer- or vector-treated
      tumor-bearing mice were followed for survival and the results were analyzed by
      the Kaplan-Meier method and the log-rank test. We found that VSV(M51R)-LacZ
      efficiently replicated and lysed human breast cancer cells but was partially
      attenuated in 4T1 cells in vitro. We also demonstrated that its maximum tolerated
      dose after intravenous infusion in normal Balb/c mice was elevated by at least
      100-fold over that of the parental VSV vector containing the wild-type M gene.
      When VSV(M51R)-LacZ was repeatedly injected intravenously into mice bearing
      syngeneic 4T1 tumors, the virus was able to infect multiple breast cancer lesions
      in the lungs without apparent toxicities, which led to significant prolongation
      of animal survival (P=.003). In conclusion, systemic administration of M mutant
      VSV is both effective and safe in the treatment of experimental breast cancer
      metastases in immune-competent mice, suggesting that further development of this
      approach may have potential for clinical application in patients.

PMID- 15565180
TI  - Cotargeting tumor and tumor endothelium effectively inhibits the growth of human
      prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination
      therapy.
AB  - Tumor-endothelial interaction contributes to local prostate tumor growth and
      distant metastasis. In this communication, we designed a novel approach to target
      both cancer cells and their "crosstalk" with surrounding microvascular
      endothelium in an experimental hormone refractory human prostate cancer model. We
      evaluated the in vitro and in vivo synergistic and/or additive effects of a
      combination of conditional oncolytic adenovirus plus an adenoviral-mediated
      antiangiogenic therapy. In the in vitro study, we demonstrated that human
      umbilical vein endothelial cells (HUVEC) and human C4-2 androgen-independent (AI)
      prostate cancer cells, when infected with an antiangiogenic adenoviral (Ad)-Flk1
      Fc vector secreting a soluble form of Flk1, showed dramatically inhibited
      proliferation, migration and tubular formation of HUVEC endothelial cells. C4-2
      cells showed maximal growth inhibition when coinfected with Ad-Flk1-Fc and Ad-hOC
      E1, a conditional replication-competent Ad vector with viral replication driven
      by a human osteocalcin (hOC) promoter targeting both prostate cancer epithelial
      and stromal cells. Using a three-dimensional (3D) coculture model, we found that
      targeting C4-2 cells with Ad-hOC-E1 markedly decreased tubular formation in
      HUVEC, as visualized by confocal microscopy. In a subcutaneous C4-2 tumor
      xenograft model, tumor volume was decreased by 40-60% in animals treated with Ad
      Flk1-Fc or Ad-hOC-E1 plus vitamin D3 alone and by 90% in a combined treatment
      group, compared to untreated animals in an 8-week treatment period. Moreover,
      three of 10 (30%) pre-established tumors completely regressed when animals
      received combination therapy. Cotargeting tumor and tumor endothelium could be a
      promising gene therapy strategy for the treatment of both localized and
      metastatic human prostate cancer.

PMID- 15565181
TI  - Use and specificity of breast cancer antigen/milk protein BA46 for generating
      anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based
      gene loading of dendritic cells.
AB  - Antigen-targeted immunotherapy is an emerging treatment for breast cancer.
      However, useful breast cancer antigens are only found in a subset of cancer
      patients. BA46, also known as lactadherin, is a membrane-associated glycoprotein
      that is expressed in most breast cancer cells but not in general hematopoietic
      cell populations. Moreover, it is much more difficult to generate CTLs against
      self-antigens. We wished to determine if the use of recombinant adeno-associated
      virus (rAAV) type 2 vectors for gene-loading of dendritic cells (DCs) could
      generate rapid, effective cytotoxic T lymphocytes (CTLs) against BA46. We were
      able to demonstrate that AAV/BA46/Neo-loading of DCs resulted in: (1) BA46
      expression in DCs, (2) chromosomal integration of the AAV/BA46/Neo vector within
      DCs, (3) strong, rapid BA46-specific, MHC class I-restricted CTLs in only 1 week,
      (4) T-cell populations with significant interferon-gamma (IFN-gamma) expression
      but low IL-4 expression, (5) high CD80 and CD86 expression in DCs, and (6) high
      CD8:CD4 and CD8:CD56 T cell ratios. These data suggest that rAAV-loading of DCs
      may be useful for immunotherapeutic protocols against self-antigens in addition
      to viral antigens and that the BA46 antigen is potentially appropriate for cell
      mediated immunotherapeutic protocols addressing ductal breast cancer.

PMID- 15565182
TI  - Bifidobacterium longum as an oral delivery system of endostatin for gene therapy
      on solid liver cancer.
AB  - To overcome difficulties that hampered widespread application of a specific
      delivery system in cancer gene therapy and to inhibit the growth of solid liver
      cancer, we utilized a strain of Bifidobacterium longum as a delivery system to
      transport an endostatin gene that can inhibit growth of tumor. The B. longum
      strain with the endostatin gene (B. longum-En) was taken orally by tumor-bearing
      nude mice through drencher preparation. The results showed that B. longum-En
      could strongly inhibit the growth of solid liver tumor in nude mice and prolong
      the survival time of tumor-bearing nude mice. Furthermore, tumor growth was
      inhibited more efficiently when the B. longum-En treatment included selenium.
      Enriching the B. longum-En treatment with selenium improves the activity of NK
      and T cells and stimulates the activity of IL-2 and TNF-alpha in BALB/c mice.
      These results suggest that B. longum may be a highly specific and efficient
      vector for transporting anticancer genes in cancer gene therapy.

PMID- 15565183
TI  - Intratumoral administration of immature dendritic cells following the adenovirus
      vector encoding CD40 ligand elicits significant regression of established
      myeloma.
AB  - Our previous study showed that J558 myeloma cells engineered CD40L lost their
      tumorigenicity in syngeneic mice, and the inoculation of J558/CD40L tumor cells
      further led to the protective immunity against wild tumors. In the present study,
      we investigated whether the vaccine can exert more efficient antitumor immunity
      by combination with adenovirus mediated CD40L gene therapy and immature dendritic
      cells (iDCs). The results demonstrated that intratumoral administration of iDCs 2
      days after AdVCD40L injection, not only significantly suppressed the tumor
      growth, but also eradiated the established tumors in 40% of the mice. The potent
      antitumor effect produced by the combination therapy correlated with high
      expression of MHC, costimulatory and Fas molecules on J558 cells, which was
      derived from CD40L transgene expression. In addition, transgene CD40L expression
      could dramatically induce J558 cell apoptosis. Effectively capturing apoptotic
      bodies by iDCs in vivo could induce DC maturation, prime tumor-specific CTLs and
      tend to Th1-type immune response. Finally, in vivo depletion experimentation
      suggested both CD4+ and CD8+ T cells were involved in mediating the antitumor
      immune responses of combined treatment of AdVCD40L and iDCs, with CD8+ T cells
      being the major effector. These findings could be beneficial for designing
      strategies of DCs vaccine and CD40L for anticancer immunotherapy.

PMID- 15565184
TI  - Progression of early postnatal retinal pathology in a mouse model of neuronal
      ceroid lipofuscinosis.
AB  - PURPOSE: Accumulation of autofluorescent storage material in the CNS is a
      hallmark of neuronal ceroid lipofuscinosis (NCL, Batten disease). Since the
      retina is generally the first CNS target affected in NCL and could serve as a
      means to assess early disease progression as well as potential therapeutic
      responses, we followed the course of postnatal retinal pathology in tissues from
      the CLN8 (mnd) mouse model of NCL. RESULTS: Cytoplasmic inclusions in the retinal
      ganglion cell (RGC) layer were shown by periodic acid schiff stain by P7. TUNEL
      measurements of cell death became significant at P21 (P<0.001) with most cell
      death occurring in the photoreceptor layer. Significant autofluorescence and RGC
      hypertrophy were evident in mnd mice at P0, prior to eye opening or significant
      cell death. CONCLUSION: An increased understanding of the timing, location, and
      characteristic retinal pathologies of Batten disease may lead to diagnostic and
      therapeutic advances in the clinical setting.

PMID- 15565185
TI  - Results of intravitreal tissue plasminogen activator and expansile gas injection
      for submacular haemorrhage in Thais.
AB  - PURPOSE: To study the results of intravitreal tissue plasminogen activator (tPA)
      and expansile gas injection for submacular haemorrhage in Thai patients. METHODS:
      The medical records of Thai patients who presented with submacular haemorrhage
      between January 1998 and December 2002 were reviewed. The inclusion criteria were
      acute onset of bleeding (<1 month), treatment with intravitreal injection of tPA
      solution (50-100 mug in 0.1 ml) and expansile gas (0.3-0.4 ml of 100%
      perfluoropropane or sulphur hexafluoride), and at least 6 months of follow-up.
      Our main outcome measures were best final postoperative visual acuity and
      surgical complications. RESULTS: A total of 19 eyes of 19 patients completed the
      inclusion criteria with a mean duration of 13.1 days. The causes of haemorrhage
      were age-related macular degeneration in 15 eyes (78.9%), idiopathic choroidal
      neovascularization in two eyes (10.5%), and traumatic, and valsalva retinopathy
      in one eye each (5.2%). After a mean follow-up of 13 months (range 6-39 months),
      postoperative visual acuity improved two lines or greater in 12 eyes (63.2%),
      stabilized in six eyes (31.6%) and worsened in one (5.2%). The final visual
      acuity measured 20/63 or better in 10 eyes (52.6%). The surgical complications
      were breakthrough vitreous haemorrhage (three eyes) and cataracts (three eyes),
      and two had retinal detachments. CONCLUSION: The treatment of submacular
      haemorrhage with intravitreal injection of tPA and expansile gas improved visual
      acuity in more than half of the patients. In all, 10 in 19 eyes demonstrated
      final visual acuity at a functional level.

PMID- 15565186
TI  - Familial pseudoexfoliation in Gozo.
AB  - AIMS: To describe the occurrence of pseudoexfoliation in three Gozitan families.
      METHODS: Three families with a high incidence of pseudoexfoliation were
      identified. All members of the three families who agreed to participate were
      interviewed and underwent a full ophthalmologic examination. The
      pseudoexfoliation status was classified as present, absent, or unknown. RESULTS:
      A total of 55 individuals from three separate family probands and with a male :
      female sex ratio of 5 : 4 were examined. In all, 18 had definite evidence of
      pseudoexfoliation, 17 of them bilaterally and one showing only unilateral signs.
      Age was the main risk factor, with 18 out of the 20 individuals who were over the
      age of 60 years having pseudoexfoliation, while none of the 35 who were below the
      age of 60 years had pseudoexfoliation. The ophthalmological findings varied in
      different families. Family I had a high incidence of both cataract and glaucoma,
      family II had mainly glaucoma, while in family III all individuals had cataract
      but none had evidence of glaucoma. The first generation of these three families
      were deceased but their hospital and clinical records revealed that in all three
      families the father was affected and there was no evidence of maternal
      involvement. CONCLUSIONS: In all three families, pseudoexfoliation appeared to be
      genetically transmitted as a late onset autosomal dominant trait of variable
      expression. Maternal transmission could not be confirmed in these families.

PMID- 15565187
TI  - Molteno tube obstruction due to viscoelastic after penetrating keratoplasty.

PMID- 15565188
TI  - Ethnic aspects of acute primary angle closure in a UK mulicultural conurbation.
AB  - AIM: To investigate the incidence and ethnic distribution of patients with
      symptomatic acute primary angle closure (APAC) who presented to a UK hospital
      serving a multicultural conurbation by a population-wide case series
      investigation. METHODS: Case series chart review of patients aged 30 years and
      above, who required laser peripheral iridotomy (LPI) for a primary acute angle
      closure event over a 7-year period. Demographic data for cases were compared to
      the local resident census data. RESULTS: A total of 46 local residents aged > or
      =30 years required LPI for APAC. In all, 96% of patients were Caucasian compared
      to the local resident population of 89% Caucasian. The overall annual APAC rate
      for Bolton was 4.14 cases per 100 000 population (95% CI 3.03-5.52). The
      standardised incidence ratio for the South Asian population was 0.78 (95% CI 0.02
      4.34) and 26.6 (95% CI 0.67-148.40) for the Chinese population. CONCLUSIONS: APAC
      incidence in South Asians was similar to that among Caucasians. The incidence of
      APAC patients treated in this UK department is consistent with international
      experience. Individuals of Chinese ethnicity were at an enhanced risk of APAC.
      However, these results should be interpreted with caution, as patient numbers are
      small.

PMID- 15565190
TI  - Endoscopic visualization to aid deep anterior lamellar keratoplasty.

PMID- 15565191
TI  - Food that's just for thought.

PMID- 15565193
TI  - Assessment of the cardiac patient for fitness to drive: drive subgroup executive
      summary.

PMID- 15565194
TI  - Assessment of the cardiac patient for fitness to fly: flying subgroup executive
      summary.

PMID- 15565195
TI  - Mandatory physician reporting of drivers with medical conditions: legal
      considerations.
AB  - BACKGROUND: Physicians are facing ever-increasing legal obligations in all
      Canadian jurisdictions to report patients believed to be unfit to drive a motor
      vehicle or pilot an aircraft. In most Canadian jurisdictions these statutory
      obligations are mandatory; in others, they are discretionary. OBJECTIVES: To
      provide a legal perspective on a physician's duty to report in the various
      jurisdictions in Canada. METHODS: Reporting legislation and case law from each of
      the Canadian jurisdictions were compared with respect to reporting requirements,
      physician protection and the production of medical reports. Federal legislation
      was examined in respect of the duty to report pilots deemed unfit to fly. Lastly,
      provincial guidelines and medical standards were examined for their impact on
      standard of care issues. RESULTS: While the obligations vary slightly from one
      jurisdiction to another, the majority of Canadian jurisdictions provide for
      mandatory reporting. Additionally, courts have been willing to apply and give
      considerable weight to medical guidelines, such as those formulated by the
      Canadian Medical Association and other provincial medical bodies, to determine
      the scope of a physician's obligation to report. CONCLUSIONS: In all
      jurisdictions, a physician who fails to report in circumstances where the
      physician is of the opinion that a driver is unfit faces potential quasi-criminal
      liability, civil liability and/or College disciplinary proceedings. The current
      statutory provisions and professional guidelines leave little room for the
      exercise of discretion on the part of the physician.

PMID- 15565196
TI  - Mandatory physician reporting of drivers with cardiac disease: ethical and
      practical considerations.
AB  - Many jurisdictions in Canada have enacted legislation that requires physicians to
      report their patients to the Ministry of Transport if they have a medical
      condition that may put them at increased risk to operate a motor vehicle. The
      Canadian Cardiovascular Society has published guidelines that are designed to
      assist physicians and policy-makers in their decision-making. Legislation is
      designed to protect society, and the guidelines are designed to fulfill that
      mandate. However, in the present paper, important issues that have not been
      addressed to date are discussed. What is the efficacy of mandatory reporting
      legislation? What are the harms done to patients who are restricted from driving?
      What are the costs of the mandatory reporting system? How can the
      scientific/technical assessment of risk be reconciled with the social/ethical
      view of risk assessment? Until these issues are addressed, important questions
      about the ethics, efficacy and cost of mandatory physician reporting will remain
      unanswered.

PMID- 15565197
TI  - Endothelial function: ready for prime time?
AB  - The strategic location of the endothelium allows it to detect changes in
      hemodynamic forces and blood-borne signals, and to respond by releasing a number
      of autocrine and paracrine substances. The balanced release of these bioactive
      factors facilitates vascular homeostasis. If disrupted, endothelial cell
      dysfunction ensues. This predisposes the vessel wall to vasoconstriction,
      leukocyte adherence, platelet activation, thrombosis, vascular inflammation and
      atherosclerosis. Given the central role of the endothelium in the development and
      progression of atherosclerosis, endothelial function testing may serve as a
      useful biomarker of atherosclerotic disease. The present review highlights the
      current modalities used in assessing endothelial function, explores how
      endothelial function may serve as a biomarker for atherosclerosis, comments on
      the prognostic relevance of endothelial function and describes its use in the
      clinical setting.

PMID- 15565198
TI  - Bridging American-Canadian health care outcome differences: is there really a
      gap?

PMID- 15565199
TI  - Portrayal of female physicians in cardiovascular advertisements.
AB  - BACKGROUND: Despite increasing numbers of female medical school graduates, few
      women enter cardiovascular specialties. Pharmaceutical promotion may influence
      physician behaviour. It is unclear how female physicians are represented in
      cardiovascular advertisements, which may, in turn, influence physician
      perceptions. OBJECTIVES: To determine if female and male physicians are equally
      represented in cardiovascular advertisements. METHODS: All cardiovascular
      advertisements from American editions of general medical and cardiovascular
      journals published between January 1, 1996, and June 30, 1998, were examined. For
      each unique advertisement, the total number of journal appearances and the number
      of appearances in journals' premium positions were recorded. The role, sex, age
      and race of the primary figure featured in the advertisement were noted. RESULTS:
      Nine hundred nineteen unique advertisements were identified, 35 of which depicted
      a physician as the primary figure. Six (17%, 95% CI 8.1% to 32.7%) of these
      advertisements portrayed a female physician, while 29 (83%, 95% CI 67.3% to
      91.9%) depicted a male physician (P<0.001). Female physician advertisements
      appeared in journals 39 times (20.7%; 95% CI 2.8% to 43.5%), while male physician
      advertisements appeared 149 times (79.3%; 95% CI 56.5% to 97.2%) (P=0.01). The
      odds ratio for a female physician advertisement appearing in a premium position
      compared with a male physician advertisement was 0.25 (95% CI 0.09 to 0.68).
      CONCLUSION: The relative paucity of female physicians in cardiovascular
      advertisements is a concern because it may both reflect and reinforce sex
      asymmetries in cardiovascular specialties.

PMID- 15565200
TI  - Validation of a new ultrasound method for the measurement of carotid artery
      intima medial thickness and plaque dimensions.
AB  - BACKGROUND: Carotid ultrasound is an accepted method for the detection of
      subclinical atherosclerosis. Valid methods that allow quantitation of carotid
      atheroma burden may be useful for stratifying risk. OBJECTIVE: To validate the
      results of intima medial thickness (IMT) and plaque measurements using a newly
      created software algorithm by comparing them with those obtained using a
      previously validated method. METHODS: Carotid ultrasound videotapes (n=24) were
      analyzed by experienced observers using a validated method and a new method.
      Ultrasound parameters were compared by measuring the difference +/- SD to yield
      indexes of accuracy and precision. Performance was also assessed using
      correlation and Bland-Altman analyses. RESULTS: Average IMT (n=24), plaque area
      (n=46), and several indexes that integrate IMT and plaque measurements were all
      found to be comparable with measurements obtained using the previously validated
      method. For example, the plaque area showed excellent accuracy and precision (
      0.17+/-2.0 mm2, P=0.56), excellent correlation (r=0.98, standard error of the
      estimate = 2.01 mm2, P<0.001) and no evidence of bias using Bland-Altman analyses
      (Spearman's rho = 0.04, P=0.82). CONCLUSIONS: A new algorithm for the
      quantitation of carotid atheroma burden yields results that are comparable with
      those of a previously validated and widely used method. Availability of valid
      tools for measuring carotid ultrasound should facilitate the incorporation of
      this procedure into clinical risk stratification paradigms.

PMID- 15565201
TI  - An overview of the role of insulin in the treatment of hyperglycemia during acute
      myocardial ischemia.
AB  - Hyperglycemia on admission to the coronary care unit is associated with poor
      outcome. It has now been reasonably well established that intravenous insulin
      infusion during acute myocardial infarction has a protective role and reduces
      mortality. The present article reviews the current understanding of the
      cardioprotective effect of insulin and the recent advances in this area.

PMID- 15565202
TI  - Interrupted aortic arch in an adolescent male.
AB  - Interrupted aortic arch (IAA) is an uncommon and usually lethal congenital
      malformation. The present report describes an unusual case of IAA, an aneurysmal
      ascending aorta and a bicuspid aorta in a 15-year-old boy. He presented with
      general malaise, weakness of his legs, headache and hypertension that began six
      months earlier. He had suffered from effort intolerance since childhood. A three
      dimensional gadolinium contrast-enhanced magnetic resonance angiogram
      demonstrated IAA and a markedly developed collateral circulation. IAA is an
      uncommon disease that is rarely encountered in an adolescent patient with
      nonspecific symptoms or hypertension. The present case also shows the clinical
      value of three-dimensional gadolinium contrast-enhanced magnetic resonance
      angiography for noninvasive assessment of the aortic arch, and magnetic resonance
      angiography can replace angiography in the assessment of aortic arch anomalies
      and visualization of well-developed collaterals.

PMID- 15565203
TI  - Asystole associated with cluster headache.
AB  - A 43-year-old man with asystole and syncope occurring during cluster headache
      attacks is reported. The asystole and syncope attacks disappeared completely
      following prophylactic therapy with methysergide maleate. To the authors'
      knowledge, the present case is unique in associating asystole with cluster
      headache attacks and may be due to hyperactivity of the parasympathetic system.

PMID- 15565204
TI  - Primary prevention.

PMID- 15565205
TI  - Long-term prognosis of early-onset Crohn's disease diagnosed in childhood or
      adolescence.
AB  - Long-term follow-up data on Crohn's disease diagnosed before 20 years of age is
      limited. Mortality, intestinal malignancy and the need for resection were
      assessed in 224 patients with early-onset disease (96 males, 42.9%; 128 females,
      57.1%). Mean follow-up was 12.2 years; more than 50% of patients were seen for
      over 10 years (almost 10% for over 25 years). Most patients were diagnosed from
      ages 13 to 19 years, rather than in childhood. Ileocolonic disease was most
      common (128 of 224; 57.1%), while upper tract involvement (42 of 224; 18.8%) was
      frequent. Complex disease with strictures (28.6%) or penetrating complications
      (46.4%) was common. To date, one patient with early-onset disease died from a
      drug overdose and one developed rectal cancer, but epithelial dysplasia has not
      been reported in endoscopic biopsies or resected intestine. One or more
      intestinal resections were required in 126 patients (56.3%; 58 males and 68
      females). More than one resection was needed in 52 patients (23.2%). The mean
      time from diagnosis to first resection was 4.2 years and from first to second
      resection was 6.6 years, with most resections required in the first two years.
      Most patients who needed one or more resections had ileocolonic disease and had
      complex stricturing or penetrating disease. Information on long-term follow-up of
      early-onset Crohn's disease is crucial to avoid the direct extrapolation of adult
      data to children and adolescents.

PMID- 15565206
TI  - Management of polycystic liver disease.
AB  - Polycystic liver disease (PCLD) is characterized by multiple cysts throughout the
      liver. Patients may develop chronic intractable symptoms that may be
      debilitating. Others may develop medical complications that necessitate
      intervention. There is a variety of nonsurgical and surgical treatment options
      for symptomatic or complicated PCLD, which range from cyst aspiration and
      fenestration to liver transplantation. Studies have described variable efficacy
      and morbidity. Currently, there are no guidelines for the management of PCLD
      patients and the optimal intervention is controversial. This article reviews the
      pathogenesis, classification and spectrum of treatment options for PCLD.

PMID- 15565207
TI  - D(-)-lactic acid-producing probiotics, D(-)-lactic acidosis and infants.
AB  - There is mounting evidence that ingestion of selected probiotics can modify
      disease morbidity for specific conditions affecting humans, and there is growing
      interest in the amelioration or prevention of disease with probiotics. Modulation
      in gene expression of the cellular elements of the intestinal mucosa and
      interbacterial interactions are leading theories as to the mechanism whereby
      probiotics can effect benefit for the host. Furthermore, gene-environmental
      interactions are considered to be important in the development of disease in
      those at genetic risk. With the intestinal tract harbouring large numbers of
      bacteria, alteration of the microbial environment with probiotic microbes is
      being considered as a controllable factor that may limit disease expression for
      those at genetic risk. This reasoning has led to interest in the administration
      of probiotics to infants. However, there are significant developmental changes
      occurring in many organ systems from the time of parturition and during the first
      months of life. Because there is little in the published scientific medical
      literature regarding the effects of long-term administration of probiotics to
      infants, potential problems must be considered; one such issue is that of
      administration of D(-)-lactate-producing probiotics. An appraisal of the current
      knowledge of this potential adverse effect is the subject of this communication.

PMID- 15565208
TI  - Deadaption and readaptation with lactose, but no cross-adaptation to lactulose: a
      case of occult colonic bacterial adaptation.
AB  - The standard 3 h breath hydrogen (3hBH2) test distinguishes lactose maldigesters
      from lactose digesters. However, multiple factors impact on BH2 and care is
      needed to exclude a priori variables. When these factors are controlled, a
      negative BH2 test implies lactase persistent status or lactase nonpersistent
      status with colonic adaptation. A case of a Sicilian man who tested negative
      (lactase persistent status confirmed) on an initial 50 g lactose challenge is
      described. It was observed that he consumed 28.1 g lactose/day before testing. He
      subsequently underwent five additional challenge tests in the course of the next
      10 months. In four tests the dose intake of lactose was varied upon instruction,
      and in the fifth test a 30 g lactulose challenge was carried out. It was
      demonstrated that on radically decreasing lactose intake, a full lactase
      nonpersistent status was unmasked. Output of 3hBH2 varied inversely with daily
      lactose intake. Finally, at a time when he was readapted to lactose, there was no
      discernible adaptation to lactulose challenge. It was concluded that 'occult'
      colonically adapted subjects may contribute to negative BH2 tests. There is a
      relationship between variation in lactose intake and the results of BH2 testing.
      Finally, there was no cross-adaptation to lactulose challenge when lactose was
      used as the adapting sugar.

PMID- 15565209
TI  - Octreotide in intestinal lymphangiectasia: lack of a clinical response and
      failure to alter lymphatic function in a guinea pig model.
AB  - Intestinal lymphangiectasia, which can be classified as primary or secondary, is
      an unusual cause of protein-losing enteropathy. The main clinical features
      include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical
      management generally includes a low-fat diet and supplementation with medium
      chain triglycerides. A small number of recent reports advocate the use of
      octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used
      in these studies; although octreotide can alter splanchnic blood flow and
      intestinal motility, its actions on lymphatic function has never been
      investigated. A case of a patient with intestinal lymphangiectasia who required a
      shunt procedure after failing medium chain triglycerides and octreotide therapy
      is presented. During the management of this case, all existing literature on
      intestinal lymphangiectasia and all the known actions of octreotide were
      reviewed. Because some of the case reports suggested that octreotide may improve
      the clinical course of intestinal lymphangiectasia by altering lymphatic
      function, a series of experiments were undertaken to assess this. In an
      established guinea pig model, the role of octreotide in lymphatic function was
      examined. In this model system, the mesenteric lymphatic vessels responded to 5
      hydroxytryptamine with a decrease in constriction frequency, while histamine
      administration markedly increased lymphatic constriction frequency. Octreotide
      failed to produce any change in lymphatic function when a wide range of
      concentrations were applied to the mesenteric lymphatic vessel preparation. In
      conclusion, in this case, octreotide failed to induce a clinical response and
      laboratory studies showed that octreotide did not alter lymphatic function. Thus,
      the mechanisms by which octreotide induced clinical responses in the cases
      reported elsewhere in the literature remain unclear, but the present study
      suggests that it does not appear to act via increasing lymphatic pumping.

PMID- 15565210
TI  - Granulomatous bronchiolitis with necrobiotic pulmonary nodules in Crohn's
      disease.
AB  - A 37-year-old man with extensive Crohn's disease of the stomach, small and large
      intestine for almost a decade developed respiratory symptoms and radiological
      findings suggestive of pneumonia that failed to resolve with antibiotic
      treatment. Computed tomography scanning of his lungs showed extensive changes
      with cavitated parenchymal nodules. Histological evaluation of an open lung
      biopsy showed granulomatous bronchiolitis and pulmonary necrobiosis. Treatment
      with steroids and immunosuppression resulted in complete resolution of his
      clinical symptoms of pneumonia and abnormal computed tomography imaging changes.
      Granulomatous bronchiolitis and necrobiotic nodules may be a manifestation of
      Crohn's disease in the absence of microbial agents, including mycobacteria or
      fungal agents. While a multiplicity of complex pulmonary changes may occur in
      Crohn's disease, their clinical recognition and precise pathological definition
      may be particularly important if treatment with a biological agent, such as
      infliximab, is being considered.

PMID- 15565212
TI  - There may be a way to say "NO" to gastric injury associated with the combined use
      of aspirin and cyclooxygenase-2 inhibitors.

PMID- 15565213
TI  - Nanoelectrodes, nanoelectrode arrays and their applications.
AB  - This review deals with the topic of ultrasmall electrodes, namely nanoelectrodes,
      arrays of these and discusses possible applications, including to analytical
      science. It deals exclusively with the use of nanoelectrodes in an
      electrochemical context. Benefits that accrue from use of very small working
      electrodes within electrochemical cells are discussed, followed by a review of
      methods for the preparation of such electrodes. Individual nanoelectrodes and
      arrays or ensembles of these are addressed, as are nanopore systems which seek to
      emulate biological transmembrane ion transport processes. Applications within
      physical electrochemistry, imaging science and analytical science are summarised.

PMID- 15565214
TI  - Mediated amperometric immunosensing using single walled carbon nanotube forests.
AB  - A prototype amperometric immunosensor was evaluated based on the adsorption of
      antibodies onto perpendicularly oriented assemblies of single wall carbon
      nanotubes called SWNT forests. The forests were self-assembled from oxidatively
      shortened SWNTs onto Nafion/iron oxide coated pyrolytic graphite electrodes. The
      nanotube forests were characterized using atomic force microscopy and resonance
      Raman spectroscopy. Anti-biotin antibody strongly adsorbed to the SWNT forests.
      In the presence of a soluble mediator, the detection limit for horseradish
      peroxidase (HRP) labeled biotin was 2.5 pmol ml(-1) (2.5 nM). Unlabelled biotin
      was detected in a competitive approach with a detection limit of 16 nmol ml(-1)
      (16 microM) and a relative standard deviation of 12%. The immunosensor showed low
      non-specific adsorption of biotin-HRP (approx. 0.1%) when blocked with bovine
      serum albumin. This immunosensing approach using high surface area, patternable,
      conductive SWNT assemblies may eventually prove useful for nano-biosensing
      arrays.

PMID- 15565215
TI  - Hydrophobic silica sol-gel films for biphasic electrodes and porotrodes.
AB  - Hydrophobic sol-gel films from methyltrimethoxysilane (MTMOS) are deposited onto
      glass and tin-doped indium oxide (ITO) coated glass substrates. Uniform and
      microporous films of ca. 200 nm thickness are obtained and investigated by
      scanning electron microscopy and by electrochemical techniques. From cyclic
      voltammograms for the oxidation of ferrocenedimethanol in aqueous 0.1 M KNO3
      apparent diffusion coefficients and free volume data for processes within the
      film are derived and it is demonstrated that the film morphology can be
      controlled by the deposition timing. Two novel types of biphasic electrodes for
      observing liquid/liquid ion transfer reactions are introduced: (i) an ITO
      electrode coated with a hydrophobic sol-gel film and (ii) a hydrophobic sol-gel
      film on glass sputter-coated with 20 nm porous gold (porotrode). For the t
      butylferrocene redox system deposited in the form of an organic liquid, very low
      and morphology dependent current responses are observed on modified ITO
      electrodes. However, the porotrode system allows biphasic electrode reactions to
      be driven with high efficiency and with no significant morphology effect of the
      hydrophobic sol-gel film. This type of nanofilm-modified electrode system will be
      of interest for biphasic sensor developments.

PMID- 15565216
TI  - Solvent effects on charge transport through solid deposits of [Os(4,4'-diphenyl
      2,2'-dipyridyl)2Cl2].
AB  - Mechanically attached, solid-state films of [Os(4,4'-diphenyl-2,2'
      dipyridyl)2Cl2] have been formed on gold macro- and microelectrodes and their
      voltammetric properties investigated. The voltammetric response of these films
      associated with the Os(2+/3+) redox reaction is reminiscent of that observed for
      an ideal reversible, solution phase redox couple only when the contacting
      electrolyte contains of the order of 40% v/v of acetonitrile (ACN). The origin of
      this effect appears to involve preferential solvation of the redox centres by
      acetonitrile which facilitates the incorporation of charge compensating
      counterions. Scanning electron microscopy reveals that voltammetric cycling in
      40:60 ACN-H2O containing 1.0 M LiClO4 as the electrolyte induces the formation of
      microcrystals. Voltammetry conducted under semi-infinite linear diffusion
      conditions has been used to determine the apparent diffusion coefficient, Dapp,
      for homogeneous charge transport through the deposit. The dynamics of charge
      transport decrease with increasing film thickness but appear to increase with
      increasing electrolyte concentration. These observations suggest that ion
      transport rather than the rate of electron self-exchange limit the overall rate
      of charge transport through these solids. When in contact with 40:60 ACN-H2O
      containing 1.0 M LiClO4 as electrolyte, Dapp values for oxidation and reduction
      are identical at 1.7 +/- 0.4 x 10(-12) cm2 s(-1). In the same electrolyte, the
      standard heterogeneous electron transfer rate constant, k(o), determined by
      fitting the full voltammogram using the Butler-Volmer formalism, is 8.3 +/- 0.5 x
      10(-7) cm s(-1). The importance of these results for the rational design of solid
      state redox active materials for battery, display and sensor applications is
      considered.

PMID- 15565217
TI  - The application of a SERS fiber probe for the investigation of sensitive
      biological samples.
AB  - The applicability of an etched and silver or gold coated SERS fiber probe in
      combination with a commercially available laboratory micro-Raman setup or a home
      built mobile micro-Raman setup to perform on-site field measurements was
      evaluated and successfully tested on different biological samples. The SERS fiber
      probe allows one to perform measurements with high spatial resolution.
      Simultaneously, the laser power used for Raman spectroscopy on biological samples
      as compared with conventional Raman experiments can be reduced by more than two
      orders of magnitude. This experimental arrangement was tested to investigate
      sensitive biological samples like mint plants (Bergamot mint, spear mint) and
      citrus fruits (kumquat). Furthermore, traces of fungicides on wine leaves were
      detected by means of such a SERS fiber probe setup.

PMID- 15565218
TI  - Measurement of nitric oxide by 4,5-diaminofluorescein without interferences.
AB  - The fluorescent reagent 4,5-diaminofluorescein (DAF-2) has been widely used for
      specific and quantitative measurements of nitric oxide (NO) in biological
      tissues. Recently it was reported that dehydroascorbic acid (DHA) and ascorbic
      acid (AA) interfere with the measurement of NO using DAF-2. A new method of
      assaying NO using DAF-2 eliminates these interferences; when frozen on dry ice,
      the NO in the original solution still diffuses and can react with an adjacent
      frozen block of DAF-2, but the confounding compounds such as DHA do not. Thus,
      placing the microliter-volume frozen blocks of solutions containing NO and the
      solutions of DAF-2 adjacent to each other for 30 min results in the concentration
      dependent formation of fluorescent product (DAF-2T) from the reaction of NO with
      DAF-2. The product has been characterized and the method validated using both
      fluorescence spectroscopy and capillary electrophoresis with laser induced
      fluorescence detection. With this approach, the presence of DHA and AA does not
      interfere with NO measurements, and product formation is inhibited in the
      presence of NO scavengers added to either of the solutions before freezing. The
      contactless DAF-2 method successfully assays NO in nitric oxide synthase-positive
      vertebrate and invertebrate tissues. This method allows nondestructive NO
      detection in biological samples that can subsequently be used for morphological
      and/or biochemical studies.

PMID- 15565219
TI  - Forensic isotope ratio mass spectrometry of packaging tapes.
AB  - Pressure sensitive adhesive tape (brown parcel tape) is employed in a great many
      criminal activities such as the restraint of individuals during robbery and
      offences against the person, the enclosure of explosive devices and the packaging
      and concealment of controlled drugs. Packaging materials are ubiquitous in modern
      society and are produced in such vast quantities that it is increasingly
      difficult to distinguish between different products or to link materials to a
      common source. This study demonstrates the potential of stable isotope ratio mass
      spectrometry to characterise parcel tapes based on a number of properties. The
      carbon isotopic signature, derived from the substrate polymer, associated
      additives and adhesive is highly characteristic of a particular tape and allows
      samples from different sources to be readily distinguished. Further
      discrimination may be achieved by the incorporation of deuterium and oxygen
      isotopic data and by analysis of the isolated backing polymer. Recovery of intact
      tape from simulated forensic samples proved straightforward and the isotopic
      signature of the tape did not appear to be affected by adverse storage
      conditions.

PMID- 15565220
TI  - Chiral recognition and separation of beta2-amino acids using non-covalently
      molecularly imprinted polymers.
AB  - Non-covalently molecularly imprinted polymers (MIPs) for beta2-amino acids were
      prepared for the first time. N-(2-chlorobenzyloxycarbonyl)-(R)-beta2
      homophenylalanine (N-2-ClZ-(R)-beta2-HPhe) was imprinted with methacrylic acid
      (MAA) and/or 4-vinylpyridine (4-VPy) as the functional monomers, with ethylene
      glycol dimethacrylate (EDMA) as the cross-linker. The MIPs made with different
      ratios of MAA:4-VPy were studied in HPLC mode. The results show that MIPs made
      with 4-VPy yielded the best chiral separation factor (alpha= 1.86) for the
      template molecule. The importance for an efficient separation of pi-stacking
      interactions between the MIPs and the template molecule is demonstrated.
      Racemates of Z-alpha-amino acids and beta-amino acid analogues of the template
      were either not or poorly resolved by the MIPs, thus demonstrating the close
      three-dimensional complementarity of the MIPs' recognition sites with the
      template.

PMID- 15565221
TI  - The application of LC-NMR and LC-SPE-NMR to compositional studies of natural
      organic matter.
AB  - Non-living natural organic matter (NOM) is ubiquitous in the oceans, atmosphere,
      sediments, and soils, and represents the most abundant organic carbon reserves on
      earth. However, a large proportion is considered to be "molecularly
      uncharacterized" because the inherent complexity of NOM is problematic when
      applying conventional analytical techniques. This manuscript presents initial
      applications of LC-NMR (1H) and LC-SPE-NMR (1H) to the studies of NOM isolated
      from water and soil. LC-NMR is applied to dissolved natural organic matter (DNOM)
      collected from freshwater environments, and both LC-NMR and LC-SPE-NMR are
      applied to an alkaline soil extract. The polar and complex nature of the DNOM
      samples limits conventional reversed phase separation, which can be partially
      overcome with the use of an ion pair reagent, although such an approach further
      complicates the NMR detection. LC-SPE-NMR of the soil alkaline extract was
      encouraging, and specific components in the mixture could be assigned. This work
      demonstrates that it is both possible to separate and concentrate specific
      components in NOM such that NMR detection is possible. As NMR information will be
      critical in unraveling the novel and/or complex structures in NOM this represents
      a key analytical hurdle in this area.

PMID- 15565222
TI  - New chemical evidence for the ability to generate radical molecular ions of
      polyenes from ESI and HR-MALDI mass spectrometry.
AB  - We report here new chemical evidence for the generation of radical molecular ions
      of compounds with a conjugated pi-system (polyene) in ESI and HR-MALDI mass
      spectrometry. The oxidation potential of the neutral polyenes was calculated by
      cyclic-voltammetry and the results compared with those previously published for
      other complex conjugated compounds that have also been shown to form M*+ in ESI
      MS. This study clearly demonstrates the correlation between the oxidation
      potential and the formation of the M*+ for the polyenes studied.

PMID- 15565223
TI  - Screening flavonoid metabolites of naringin and narirutin in urine after human
      consumption of grapefruit juice by LC-MS and LC-MS/MS.
AB  - The main flavonoids in grapefruit juice, naringin and narirutin, were quantified
      by LC-MS with structural differentiation by LC-MS/MS. After human consumption of
      grapefruit juice, urine samples were collected for 24 hours and screened for
      flavonoid metabolites by LC-MS. The metabolite structures (glucuronides,
      sulfates, and glucuronide sulfates) were then confirmed via their unique
      fragmentation patterns by LC-MS/MS. To further verify the identity of the common
      aglycon (naringenin) shared by the metabolites, enzymatic hydrolysis was
      performed and the resulting products were analyzed. This work demonstrates that
      LC-MS and LC-MS/MS techniques can be used for fast metabolite screening without
      extensive sample preparation.

PMID- 15565224
TI  - Monitoring viral DNA release with capillary electrophoresis.
AB  - Viral DNA injection into host cells is one of the primary mechanisms of viral
      propagation. Drug development that targets viral propagation requires fast and
      sensitive methods for monitoring the release of viral DNA in vitro. Here we
      demonstrate the use of capillary electrophoresis (CE) for monitoring DNA release
      from virus particles. As a model for this study, we used T5 bacteriophages that
      infect the bacterium Escherichia coli K-12 by binding to the outer membrane FhuA
      receptor and then injecting DNA. DNA release from the T5 phages in vitro was
      induced by either elevated temperature or by interaction with the purified FhuA
      receptor. After DNA release, the viral samples were stained with the high
      affinity fluorescent dye YOYO-1, injected into the capillary and subjected to
      electrophoresis. YOYO-1-stained DNA generated a well-defined peak, allowing
      reliable detection of viral DNA from as few as 10(5) viral particles. The
      staining to track T5 phage DNA release exemplifies the great versatility that CE
      offers in studying viral systems. This CE-based method can be used to study
      molecular mechanisms of viral infections and to evaluate anti-viral drug
      candidates.

PMID- 15565225
TI  - Chiral ligand exchange capillary electrophoresis using borate anion as a central
      ion.
AB  - Native DL-pantothenic acid, having a 1,3-diol structure, was chirally resolved by
      ligand exchange capillary electrophoresis using (S)-3-amino-1,2-propanediol as a
      chiral selector and the borate anion as a central ion. The optimum conditions for
      both high resolution and short migration time of DL-pantothenic acid were found
      to be 200 mM (S)-3-amino-1,2-propanediol and 200 mM borate buffer (pH 9.2)
      containing 15% methanol with an applied voltage of +25 kV at 20 degrees C, using
      direct detection at 200 nm. With this system, the resolution (Rs) of racemic
      pantothenic acid was approximately 1.7. When (S)-1,2-propanediol, (S)-1,2,3
      propanetriol, (S)-1,3-butanediol or (S)-1-amino-2-propanol were used as chiral
      ligand instead of (S)-3-amino-1,2-propanediol, DL-pantothenic acid was not
      enantioseparated. When borate was replaced with Tris or butylborate, no chiral
      separation was achieved. Therefore, the ionic interaction between the amino and
      carboxyl groups of the ternary complex may play an important role in the
      enantioseparation of DL-pantothenic acid by the proposed CE system.

PMID- 15565226
TI  - Curve-fitting overlapped bands: quantification and improvement of curve-fitting
      robustness in the presence of errors in the model and in the data.
AB  - Estimation of the band parameters of overlapped bands often relies on curve
      fitting. It has been demonstrated that curve-fitting provides the maximum
      likelihood estimation of band parameters under a series of assumptions. One of
      these assumptions is that the curve-fitting model is correct and any error in the
      data is random. Under real conditions, we have to acknowledge the unavoidable
      presence of errors in the model and systematic errors in the data. Here, we
      derive an expression for the estimation of how these errors affect the quality of
      the parameters obtained from curve-fitting. In addition, we derive theoretical
      expressions to quantify the extent to which different methods can improve the
      curve-fitting robustness to these errors. The methods considered are: (i)
      deterministic and (ii) probabilistic constraints in the band parameters, (iii)
      curve-fitting band-narrowed data, and (iv) building a more accurate model. The
      theoretical expressions obtained are tested in the curve-fitting of a synthetic
      noisy spectrum with either baseline or band shape errors, and in the curve
      fitting of the experimental infrared amide I band of the membrane protein
      bacteriorhodopsin.

PMID- 15565227
TI  - Surface-enhanced Raman scattering for ultrasensitive chemical analysis of 1 and 2
      naphthalenethiols.
AB  - The results of the search for the optimal experimental conditions for
      ultrasentitive chemical analysis of 1-naphthalenethiol (1-NAT) and 2
      naphthalenethiol (2-NAT) using surface-enhanced Raman scattering (SERS) are
      discussed. The report begins with a review of the vibrational spectra, including
      infrared and Raman spectra of the target molecules, and the interpretation of the
      observed frequencies aided by local density functional theory (DFT) calculations
      at the B3LYP/6-311G(d,p) level of theory. Several metal nanostructures were
      tested for SERS activity, including island films and colloids of silver, gold and
      copper. Correspondingly, the most effective laser line for excitation in the
      visible and near infrared region was sought. The achieved detection limit for 1
      naphthalenethiol, and for 2-naphthalenethiol, on silver nanostructures is in the
      zeptomole regime.

PMID- 15565228
TI  - Capillary electrophoresis monitoring of halide impurities in ionic liquids.
AB  - Quantification of impurities in ionic liquids is a crucial task in assessing the
      reliability of physical constants and solvent properties: taking into account the
      particularities of the ionic matrix, a simple routine method using capillary
      electrophoresis (CE) is developed to determine the halide content at the ppm
      level in water-immiscible ionic liquids.

PMID- 15565229
TI  - A general chemiluminescence method for the determination of surfactants based on
      its quenching effect on the luminol-NaIO4-cyclodextrin reaction.
AB  - Here we report that all types of surfactant could be simply and sensitively
      determined, by directly quenching the chemiluminescence (CL) between luminol and
      NaIO4 in a basic solution containing one polyhydroxyl compound such as
      cyclodextrin (CD), glucose or glycerol. This specific quenching effect was
      attributed to the change of the microenvironment of the CL reaction, caused by
      the addition of various surfactants. Based on this fact, the potential use of
      this CL reaction was exemplified by the cationic surfactant CTMAB, anionic
      surfactant SDS and non-ionic surfactant Triton X-100. It was found that the
      measurable range of CTMAB, SDS and Triton X-100 were 4.0 x 10(-6)-4.0 x 10(-4) M
      by using a basic CD-luminol-NaIO4 CL reaction. With our simple setup, CTMAB, SDS
      and Triton X-100 were detectable at a concentration as low as 2 microM. Overall,
      this new CL reaction is quite promising for the post-column determination of
      surfactant mixtures.

PMID- 15565230
TI  - Multivalency in supramolecular chemistry and nanofabrication.
AB  - Multivalency is a powerful and versatile self-assembly pathway that confers
      unique thermodynamic and kinetic behavior onto supramolecular complexes. The
      diversity of the examples of supramolecular multivalent systems discussed in this
      perspective shows that the concept of multivalency is a general phenomenon, and
      that any supramolecular interaction can be employed in multivalent displays to
      attain the attractive aspects characteristic of multivalent interactions. After a
      general introduction reviewing the general aspects of multivalency, a number of
      different supramolecular multivalent complexes are discussed that highlight the
      different features of multivalent interactions. In contrast to the many
      biochemical multivalent interactions, supramolecular multivalent interactions are
      ideal to attain a quantitative and fundamental understanding of multivalency.
      Several examples in which multivalency has been utilized in supramolecular
      nanofabrication schemes are described in detail.

PMID- 15565231
TI  - Temperature regiocontrol of intramolecular cyclization of di-hydroxysecoacids.

PMID- 15565233
TI  - Photoinduced charge separation in a donor-acceptor functionalized 2,3
      diphenylbutadiene: charge transport over a doubly bifurcated pi-spacer.
AB  - By studying photoinduced charge transfer processes in 2-(4-cyanophenyl)-3-(4-N,N
      dimethylaminophenyl)-1,3-butadiene it is shown that insertion of branching points
      in a pi-conjugated pathway has a relatively small effect on the donor-acceptor
      interaction.

PMID- 15565232
TI  - Preparation of 2- and 4-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans
      having potent antagonistic activity against human leukotriene B4 BLT1 and/or BLT2
      receptors.
AB  - (E)-2-Acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan
      (4b) with a characteristic conformation and (E)-2-(2-morpholinocarbo-1
      methylvinyl)-7-ethoxycarbopropoxybenzo[b]furan ((E)-3b) were prepared and
      evaluated for their leukotriene B4(LTB4) antagonistic activity. Compound 4b
      showed potent antagonistic activity against human BLT1 and BLT2 receptors.
      Compound (E)-3b displayed selective BLT2 receptor antagonistic activity. Both
      compounds were inactive to cysteinyl LT receptors.

PMID- 15565234
TI  - Self-replication vs. reactive binary complexes--manipulating recognition-mediated
      cycloadditions by simple structural modifications.
AB  - The rate of reaction and the selectivity of a Diels-Alder cycloaddition between a
      furan and a maleimide can be enhanced by the introduction of complementary
      recognition sites on the reactant species. Subtle manipulation of other
      structural elements allows the generation of the observed rate enhancements and
      selectivities through either self-replication or formation of a pre-reactive
      binary complex.

PMID- 15565235
TI  - Controlling conformations and physical properties of meso
      tetrakis(phenylethynyl)porphyrins by ring fusion: synthesis, properties and
      structural characterizations.
AB  - The boron trifluoride-catalyzed Rothemund condensations of
      phenylpropargylaldehyde with 4,7-dihydro-4,7-ethano-2H-isoindole or 3,4
      diethylpyrrole in dichloromethane at low temperature give 5,10,15,20
      tetrakis(phenylethynyl)porphyrins bearing bicyclo[2.2.2]octadiene and octaethyl
      substituents, respectively. The former undergoes a retro Diels-Alder reaction to
      afford 5,10,15,20-tetrakis(phenylethynyl)benzoporphyrin quantitatively. The
      different conformations of the porphyrin periphery were determined by X-ray
      diffraction and their redox and spectroscopic properties have been investigated.

PMID- 15565236
TI  - Preparation of macrocyclic 15N-labelled oligoaminodeoxysaccharides as probes for
      RNA-binding.
AB  - Two macrocyclic aminoglycosides were prepared from a 1,4-butanediol linked 2
      deoxy-L-rhamnal which was O-allylated at the 4- and 4'-positions via the
      precursor allyl 3,4-di-O-acetyl-2,6-dideoxy-alpha-L-arabino-hexoside employing
      olefin metathesis and ring closing metathesis in a sequential manner. The
      macrocycles were 15N-labelled at all four amino groups in order to study
      interactions with regulatory RNA structures in solution by NMR spectroscopy. A
      key step for the introduction of the 15N-label was a reductive amination step
      using commercially available 15NH4OAc. The reductive amination proceeds with
      excellent stereocontrol. As a by-product the unusual acyclic amino nitrile was
      isolated which originated from intramolecular imine formation followed by cyanide
      addition to the intermediate C=N double bond.

PMID- 15565237
TI  - La3+-catalyzed methanolysis of O,O-diethyl S-(p-nitrophenyl) phosphorothioate and
      O,O-diethyl S-phenyl phosphorothioate. Millions-fold acceleration of the
      destruction of V-agent simulants.
AB  - The La3+-catalyzed methanolysis of two phosphorothioate derivatives, O,O-diethyl
      S-(p-nitrophenyl) phosphorothioate (4a) and O,O-diethyl S-phenyl phosphorothioate
      (4b) were studied as a function of [La3+] and pH in methanol solvent. In both
      cases the kinetics of catalyzed methanolysis maximize at pH 9.1 and a detailed
      analysis indicates that the dominant species responsible for catalysis are dimers
      formulated as La3+(2)(-OCH3)2 and La3+(2)(-OCH3)4. The catalysis is compared with
      that seen for the corresponding phosphate esters, namely paraoxon (3a) and O,O
      diethyl phenyl phosphate (3b) for which La3+ catalysis is slightly better and
      markedly worse than for 4a and 4b respectively. Overall, at s(s)pH 9.1, a 2 mmol
      dm-3 solution of La(OTf)3 with equimolar NaOCH3 provides accelerations of
      2.2x10(8)-fold, 9.7x10(6)-fold and 9.3x10(6)-fold for methanolysis of 3a, 4a and
      4b, relative to the background reaction of methoxide reacting with the three
      substrates. In each case, the P-containing product of the reactions is
      exclusively diethyl methyl phosphate. Turnover experiments with 6-fold and 100
      fold excesses of 4a and 4b respectively, methanolyzed in the presence of
      approximately 10 mmol dm-3 La3+ and equimolar NaOCH3, indicate that the reactions
      are essentially complete within 103 s and 70 min respectively. The latter
      turnover experiment with 4b corresponded to 100 turnovers in 70 min and an
      overall reaction t1/2 of 8 min. A common mechanism of reaction is postulated for
      each of the substrates which involves Lewis acid coordination of one of the La3+
      to the P=O unit, followed by nucleophilic attack by the second La3+-(-)OCH3.

PMID- 15565238
TI  - Manganese(III) acetate-mediated free radical reactions of [60]fullerene with beta
      dicarbonyl compounds.
AB  - [60]Fullerene reacted with various beta-dicarbonyl compounds in the presence of
      Mn(OAc)3*2H2O to generate dihydrofuran-fused [60]fullerene derivatives or 1,4
      bisadducts. Dihydrofuran-fused [60]fullerene derivatives 2 could be formed by
      treatment of alpha-unsubstituted beta-diketones 1a-e or beta-ketoesters 1f and 1g
      with [60]fullerene in refluxing chlorobenzene in the presence of Mn(III). Solvent
      participated unsymmetrical 1,4-bisadducts 3 were obtained through the reaction of
      [60]fullerene with dimethyl malonate 1h or alpha-substituted beta-dicarbonyl
      compounds 1i-1n in toluene. A possible reaction mechanism for the formation of
      different fullerene derivatives is proposed.

PMID- 15565239
TI  - Structural scaffold of 18-crown-6 tetracarboxylic acid for optical resolution of
      chiral amino acid: X-ray crystal analyses and energy calculations of complexes of
      D- and L-isomers of tyrosine, isoleucine, methionine and phenylglycine.
AB  - To clarify the structural scaffold of (+)-18-crown-6 tetracarboxylic acid ((+)
      18C6H4) for the optical resolution of a chiral amino acid, the crystal structures
      of its equimolar complexes with L- and D-isomers of tyrosine (Tyr), isoleucine
      (Ile), methionine (Met) and phenylglycine (PheG) were analysed by X-ray
      diffraction methods. (+)-18C6H4 took very similar conformations for all
      complexes. Although the chemical structure of (+)-18C6H4 is C2-symmetric, it took
      a similar asymmetric ring conformation of radius ca. 6.0 A. In all complexes, the
      amino group of chiral amino acids was located near the center of the ring and
      formed three hydrogen bonds and five electrostatic interactions with eight oxygen
      atoms of the ether ring and carboxyl groups. Also, the Calpha atom of chiral
      amino acids participated in Calpha-H...O interaction with the oxygen atom of (+)
      18C6H4. In contrast, the carboxyl group of chiral amino acids did not directly
      interact with (+)-18C6H4. These results indicate that the structural scaffold of
      (+)-18C6H4 for the optical resolution of chiral amino acids is mainly based on
      the mode of interaction of (+)-18C6H4 with the amino and Calpha-H groups of
      chiral amino acids. The differences in interaction pattern and binding energy
      between the L- and D-isomers of each amino acid are discussed in relation to the
      chiral recognition of (+)-18C6H4.

PMID- 15565240
TI  - Cyclodextrins containing an acetone bridge. Synthesis and study as epoxidation
      catalysts.
AB  - Three cyclodextrine derivatives (6A,6D-di-O-(prop-2-one-1,3-dienyl)-alpha
      cyclodextrin (1), 6-O-(prop-2-one-1-yl)-alpha-cyclodextrin (2) and 6A,6D-di-O
      (prop-2-one-1,3-dienyl)-beta-cyclodextrin (3)) were synthesised and investigated
      as epoxidation catalysts. The three compounds were synthesised from the
      corresponding perbenzylated cyclodextrins which were mono- or didebenzylated in
      the 6-position using Sinay's method. Reaction with NaH and methallyl chloride in
      the case of 2, or methallyl dichloride in the case of 1 and 3, followed by
      dihydroxylation, periodate cleavage and protection group removal gave the target
      compounds. All three compounds catalysed, in the presence of oxone, the
      epoxidation of a series of alkenes. Epoxidation was compared to the reaction
      catalysed by simple ketones and inhibition was studied.

PMID- 15565241
TI  - Chemistry of 1,3-diarylpropynones in superacids.
AB  - In superacids with H0=-14 to -20, it has been found that 1,3-diarylpropynones ArC
      triple bond CCOAr' are either protonated on oxygen of carbonyl groups with the
      formation of stable ions ArC triple bond CC(O+H)Ar' or undergo further
      transformations when the highly conjugated system is electron-rich enough. In the
      latter case, 3-arylindenones are produced very rapidly and with high efficiency
      (up to 95% yield in less than 30 min). The influence of the substituents Ar, Ar'
      and of the reaction conditions on the behavior of 1,3-diarylpropynones and on the
      intramolecular cyclisation have been studied. From the collected data, a
      mechanism has been proposed involving vinyl cations ArC+=CHCOAr' and/or dications
      ArC+=CHC(O+H)Ar'.

PMID- 15565242
TI  - On the addition of 4-(N,N-dimethylamino)phenyl cation to norbornene.
AB  - The photochemically generated 4-(N,N-dimethylamino)phenyl cation adds to
      norbornene giving a phenylnortricyclene and various 2-exo substituted
      phenylnorbornanes (main isomers, 3-endo-, 7-anti- and 7-syn-phenyl). Acetamides
      are obtained in MeCN and ethers in alcohols (MeOH, iso-PrOH, tert-BuOH,
      CF3CH2OH). The product distribution is closely reminiscent of that obtained in
      the solvolysis of 2-norbornyl derivatives, supporting that the reaction offers a
      novel access to a 'non classical' 2-norbornyl cation. The fate of this cation is
      determined by the basicity/nucleophilicity of the solvent.

PMID- 15565243
TI  - Synthesis and hybridization properties of oligonucleotide-perylene conjugates:
      influence of the conjugation parameters on triplex and duplex stabilities.
AB  - We report here the synthesis of oligo-2'-deoxyribonucleotides (ODNs) conjugated
      with perylene. Introduction of perylene, coupled either directly or via a propyl
      linker to the anomeric position of a 2'-deoxyribose residue, induces the
      formation of two anomers. Single incorporations of each pure anomer of these
      sugar-perylene units have been performed at either the 5'-end or an internal
      position of a pyrimidic pentadecamer. The binding properties of these modified
      ODNs with their single- and double-stranded DNA targets were studied by
      absorption spectroscopy. Double incorporations of the sugar-perylene unit most
      efficient at stabilizing the triplex and duplex structures (the beta-anomer
      involving the propyl linker) have been performed at both the 5'-end and at an
      internal position (or both the 5'- and 3'-ends) of the ODN chain. Comparison has
      been made with ODN-perylene conjugates involving either one or two perylenes
      attached via a longer polymethylene chain to either the 5'- or 3'- (or both the
      5'-and 3'-) terminal phosphate groups. The ODNs involving two perylenes are more
      efficient at stabilizing the triplex and the duplex structures than the ODNs
      involving only one perylene and, among these, the ODN-perylene conjugate
      involving two sugar-perylene units attached at both termini is the most
      efficient. The results of the fluorescence studies have shown an important
      increase in the intensity of the fluorescent signal upon hybridization of the
      ODNs involving two perylenes with either the single- or the double-stranded
      targets. This increase in the intensity of the fluorescent signal could be used
      as proof of the hybridization.

PMID- 15565244
TI  - The synthesis of angularly fused polyaromatic compounds by using a light
      assisted, base-mediated cyclization reaction.
AB  - The synthesis of substituted polyaromatic compounds that contain at least four
      benzene rings fused together in an angular fashion is described. Suzuki coupling
      of 1-bromo-3,4-dihydronaphthalene-2-carbaldehyde with a number of aromatic
      boronic acids affords products such as 1-(1,4-dimethoxy-3-methyl-2-naphthyl)-3,4
      dihydronaphthalene-2-carbaldehyde. Exposure of these dihydronaphthalenes to
      potassium tert-butoxide and DMF at 80 degrees C yields polyaromatic compounds
      such as 9,14-dimethoxynaphtho[1,2-a]anthracene.

PMID- 15565245
TI  - Preparation and reductive transformations of vinylogous sulfonamides (beta
      sulfonyl enamines), and application to the synthesis of indolizidines.
AB  - Condensation between the methiodide salts of 1-alkylpyrrolidine-2-thiones and
      ethyl [(4-methylphenyl)sulfonyl]acetate or 1-[(4-methylphenyl)sulfonyl]propan-2
      one afforded several 2-[[(4-methylphenyl)sulfonyl]methylene]pyrrolidines in good
      yield. These beta-sulfonyl enamines are sufficiently nucleophilic for cyclisation
      with internal electrophiles to give sulfone-substituted indolizines, potentially
      useful scaffolds for alkaloid synthesis. The carbon-carbon double bond in
      vinylogous sulfonamides was reduced stereoselectively either by catalytic
      hydrogenation or by treatment with sodium borohydride to yield beta-sulfonyl
      amines. The sulfone group in beta-acyl-beta-sulfonyl enamines could be removed by
      hydrogenolysis with sodium amalgam in THF-methanol to give enaminones.

PMID- 15565247
TI  - Synthesis and reactions of polymer-bound Ph3P=C=C=O: a quick route to tenuazonic
      acid and other optically pure 5-substituted tetramates.
AB  - Polystyrene-bound cumulated ylide Ph3PCCO was prepared on a large scale in two
      steps. It reacts with Grignard compounds, amines and alcohols to give immobilized
      acyl, amide and ester ylides, respectively. Their Wittig reactions lead to
      alkenes free of phosphane oxide. Optically pure 5-substituted tetramates were
      obtained from reactions of resin-bound Ph3PCCO with alpha-ammonium esters in one
      step. The mycotoxin (-)-tenuazonic acid was accordingly prepared in just three
      steps.

PMID- 15565248
TI  - Determination of the rate constant for ring opening of an alpha-cyclopropylvinyl
      radical.
AB  - The rate constant for ring opening of the 1-(trans-2-phenylcyclopropyl)ethen-1-yl
      radical, 4, generated by photolysis of the corresponding vinyl iodide 2, is
      reported. The value of the rate constant was determined by the tin hydride method
      and was found to be (1.6+/-0.2)x10(10) s-1, one order of magnitude smaller than
      the rate constant for rearrangement of the trans-2-phenylcyclopropylcarbinyl
      radical.

PMID- 15565250
TI  - Biosynthesis of pantothenate.
AB  - Pantothenate is an essential metabolite for all biological systems, however, the
      biosynthetic pathway is limited to plants, eubacteria and archaea. This suggests
      that the pathway is a strong candidate for the discovery of novel antibiotic and
      herbicidal compounds. The enzymology of this short pathway in both bacteria and
      plants is discussed in detail. In addition a short survey of studies of the whole
      pathway, and a discussion of both the metabolism and the transport of
      pantothenate are included.

PMID- 15565251
TI  - Chemical aspects of amine oxidation by flavoprotein enzymes.
AB  - The mechanism of amine oxidation by flavoprotein enzymes is critically analysed
      through analysis of available experimental data. The review assesses available
      evidence for radical and polar mechanisms, drawing on data from model reactions,
      kinetic and spectroscopic approaches, structural and mutagenesis studies. The
      review focused on studies of mammalian monoamine oxidases and the bacterial
      enzymes trimethylamine dehydrogenase, monomeric sarcosine oxidase and
      dimethylglycine oxidase.

PMID- 15565252
TI  - Biological activities of pyridoacridines.
AB  - This review consolidates biological activity data reported for pyridoacridine 1
      molecules in the literature from 1983-2003 into several tables with brief
      discussions of assays used and results obtained. This review summarizes recent
      progress in structure activity relationships for analogues of amphimedine 2 and
      ascididemin 3 classes of pyridoacridines and correlates reported molecular
      mechanisms of action with biological activities.

PMID- 15565253
TI  - The Lycopodium alkaloids.
AB  - Lycopodium alkaloids are quinolizine, or pyridine and alpha-pyridone type
      alkaloids. Some Lycopodium alkaloids are potent inhibitors of
      acetylcholinesterase (AChE). Huperzine A (HupA) is reported to increase
      efficiency for learning and memory in animals, and it shows promise in the
      treatment of Alzheimer's disease (AD). 201 Lycopodium alkaloids from 54 species
      of Lycopodium (sensu lato) have been reported so far. This review is intended to
      to cover the chemical, pharmacological and clinical research on Lycopodium
      alkaloids reported in the literature from the spring of 1993 to August 2004.
      Structures of 81 new Lycopodium alkaloids are presented, classified and analyzed.
      The structural characters and biogenetic relationships of the four major
      Lycopodium alkaloid groups (lycopodine, lycodine, fawcettimine and miscellaneous)
      are discussed. Bioactivities of Lycopodium alkaloids, especially HupA, are
      summarized. In particular, the effect of HupA and other cholinesterase inhibitors
      (anti-AD drugs) on acetylcholine esterase (AChE) activity in the rat cortex and
      butylcholine esterase activity are compared. Structure-activity relationships and
      structure modifications of HupA and its analogs are described. Information on
      clinical trials with HupA and its derivative ZT-1 is presented. The state of HupA
      availability and recent advances in in vitro propagation of HupA producing plants
      are outlined. Finally, hypotheses about Lycopodium alkaloid biosynthetic pathways
      are discussed.

PMID- 15565254
TI  - Fluorometabolite biosynthesis and the fluorinase from Streptomyces cattleya.
AB  - This review outlines the recent developments in uncovering the enzymes and
      intermediates involved in fluorometabolite biosyntheses in the bacterium
      Streptomyces cattleya. A particular emphasis is placed on the purification and
      characterisation of the fluorinase, the C-F bond forming enzyme which initiates
      the biosynthesis. Nature has hardly developed a biochemistry around fluorine, yet
      fluorinated organics are important commercial entities, therefore a
      biotransformation from inorganic to organic fluorine is novel and of contemporary
      interest.

PMID- 15565255
TI  - Diterpenoids.
AB  - This review covers the isolation and structures of diterpenoids including
      labdanes, clerodanes, abietanes, pimaranes, kauranes, gibberellins,
      cembranolides, taxanes and marine diterpenoids. The literature from January to
      December, 2003 is reviewed and 164 references are cited.

PMID- 15565256
TI  - Carbapenem-resistant Pseudomonas aeruginosa outbreak in an intensive care unit of
      a teaching hospital.
AB  - The genetic similarity of carbapenem-resistant Pseudomonas aeruginosa strains
      isolated in the Hospital Universitario Sao Francisco, Braganca Paulista, Sao
      Paulo, Brasil, was evaluated by pulsed field gel electrophoresis (PFGE). A unique
      clone was detected among 5 of 7 isolates, suggesting that cross-contamination
      might have played a role in the spread of carbapenem-resistant P. aeruginosa
      strains. Interestingly, a similar PFGE pattern was encountered in a P. aeruginosa
      strain isolated from Hospital Sao Paulo that was used as a PFGE control.

PMID- 15565257
TI  - Audit of antibiotic use in a Brazilian University Hospital.
AB  - A cohort study was carried out at the Marilia Medical School Hospital. In the
      first phase the pattern of antibiotic use was evaluated. Antibiotics were
      prescribed for 55.4% of the patients; antibiotic combinations were used in 43%.
      Therapeutic use of antibiotics was considered inadequate in 27%. Respiratory and
      skin infections were the most frequently diagnosed. In up to 31% of the cases the
      treatment of respiratory infections was considered inadequate. The surgical use
      of antibiotic prophylaxis was evaluated in the second phase. Prophylaxis was
      indicated in 73.2% of the surgeries. The antibiotics most used for prophylaxis
      were first generation cephalosporins. In 78.9% of the surgeries, the antibiotic
      was correctly chosen. In 15.9% of the surgeries, the initial antibiotic
      administration was correctly timed. The use of antibiotics in the post-operative
      period was appropriate in 29.8% of the cases. The independent risk factors for
      surgical site infection (SSI), as determined by logistic regression analysis
      adjusted to class of wound risk, were the choice of antibiotic to be used
      prophylactically and the duration of antibiotic treatment in the post-operative
      period. Those who received appropriate prophylactic antibiotics had a lower rate
      of SSI than those who received innapropriated antibiotics [RR=0.49/95%; CI=0.25
      0.90]. Patients who received prophylactic antibiotics correctly in the post
      operative period had a lower risk of SSI than those who did not [RR=0.21/95%;
      CI=0.70-0.63]. The mean length of hospital stay was shorter among patients whose
      prophylactic treatment was correctly employed than among for which it was not
      [6.1 (+/-9.8) and 11.1 (+/-13.5) days, p=0.25].

PMID- 15565258
TI  - Evaluation of the genotypic pattern of HIV-1 resistance in AIDS patients failing
      antiretroviral therapy.
AB  - We analyzed the first 96 patients tested for HIV resistance to antiretroviral
      therapy in three Brazilian states. The HIV-1 reverse transcriptase (RT) and
      protease (PR) were sequenced by using the ABI ViroSeq system. The drugs
      previously used for each patient were recorded and correlated with the mutations
      found in the samples. Viral load (VL) and CD4 count were also recorded. Only one
      patient had the wild type sequence. The most prevalent mutations were: 184V
      (59%), 41L (47.9%), 63P (53%), 215Y (50%), 36I (46%), 10I (35%), 67N (42%), 77I
      (37%), 90M (36%) and 210W (33%). A positive correlation between the number of
      previously used ARVs and the number of mutations was observed (p<0.05).
      Associations between mutations and ARV drugs were identified at positions 69,
      118, 184 and 215 with previous exposure to NRTI, mutations at positions 98, 100,
      103, 181 and 190 with previous NNRTI use and at positions 10, 20, 30, 46, 53, 54,
      71, 73, 82, 84, 88 and 90 with previous PI therapy (p<0.05). Previous exposure to
      ARV drugs was associated with previous genotypic resistance to specific drugs,
      leading to treatment failure in HIV patients. Genotypic resistance was clearly
      associated with virological and immunological failure.

PMID- 15565259
TI  - Prevalence of mycobacteremia in patients with AIDS and persistant fever.
AB  - In the advanced stages of AIDS, characterized by severe immunodepression,
      tuberculosis (TB) may present with a clinical picture of septic shock, due to
      typical bacteremia. Hematogenic dissemination of mycobacteria is frequent in
      immunodepressed patients with TB or disseminated mycobacteriosis, leading to
      increased positivity in detection by automated blood culture. The objective of
      our study was to determine the prevalence of mycobacteremia in patients with AIDS
      and with prolonged fever seen at the Emilio Ribas Institute of Infectology.
      Patients with a history of daily fever (> or = 37.8 degrees C), lasting more than
      30 days, and with CD4+ helper lymphocyte counts below 200 cells/mL, were selected
      from February 2001 to March 2002. A 5 mL peripheral blood sample was collected
      from each patient for mycobacterial blood culture by an automated method, using
      the BACTEC 9000 MB and MB/BACT techniques. Forty-five patients aged on average 35
      years, most of them males, were included in the study. The mean T CD4+ lymphocyte
      count was 58 cells/mL. Among the samples submitted to blood culture, 30% gave M.
      tuberculosis growth, with 62% sensitivity. Among the patients with a negative
      blood culture, nine had received a diagnosis of TB by another method. Automated
      blood culture proved to be a technique of relevant diagnostic value for M.
      tuberculosis in patients with prolonged fever in advanced stages of AIDS. The
      method is simple, and it helps the physician to select the best therapeutic
      option.

PMID- 15565260
TI  - Nontuberculosis mycobacteria at a multiresistant tuberculosis reference center in
      Bahia: clinical epidemiological aspects.
AB  - OBJECTIVE: Examine the prevalence and clinical/epidemiological aspects of
      patients with nontuberculous mycobacteria (NTM) isolated from sputum provided by
      an outpatient clinic specializing in the treatment of multiresistant tuberculosis
      (MRTB) in Bahia, Brazil. METHODS: All patients followed at the MRTB outpatient
      clinic of the Octavio Mangabeira Specialized Hospital (HEOM) were evaluated
      retrospectively from July 1998 to July 2003. All patients underwent direct
      examinations and cultures to identify the mycobacteria species found during
      initial and subsequent evaluations. The following variables were recorded: age,
      gender, clinical symptoms and signs, pre-existing lung disease, prior TB
      treatment, HIV serology, and NTM species. Categorical and quantitative variables
      were respectively characterized using proportions and measures +/- SD. RESULTS:
      NTM were isolated in 19 of 231 patients (8.2%; 95%CI: 5.2%-12.3%), with the
      following species distribution: 58% (11/19) M. chelonae/abscessus; 16% (3/19) M.
      avium-intracellular complex; 16% (3/19) M. kansasii; and 11% (2/19) M. fortuitum.
      HIV serology was positive for just one patient (5%), from whom M.
      chelonae/abscessus was isolated. Productive coughing was observed in all cases.
      American Thoracic Society (ATS) diagnostic criteria for NTM lung disease were
      observed in 14 patients (74%). CONCLUSION: The prevalence of NTM isolated from
      patients referred to the MRTB outpatient clinic in Bahia was 8.2% (CI 95%: 5.2%
      12.3%); rapid-growth mycobacteria (M. chelonae/M. fortuitum) were the most
      frequently isolated (68%).

PMID- 15565261
TI  - Diagnosis of pulmonary tuberculosis by score system in children and adolescents:
      a trial in a reference center in Bahia, Brazil.
AB  - Since 2002, the Brazilian Ministry of Health has recommended a score system for
      tuberculosis diagnosis of children and adolescents that does not need
      bacteriological positivity, because most cases in this age group have few
      bacteria. An observational, transversal study was carried out at the outpatient
      health care service of the reference medical service in Salvador, Bahia,
      including 164 patients with pulmonary tuberculosis, with ages ranging between 1
      and 15 years of age, who were treated from 1990 to 2001. The gold standard used
      to establish the diagnosis was clinical, radiological, epidemiological and based
      on follow-up data. The score system for diagnosis purposes was tested
      retrospectively. The median age and the average age of the 164 patients were 6
      and 6.62 years (SD +/- 4.33), respectively. About 65% of the sample reported a
      history of close contact with a tuberculous adult. The BCG vaccine coverage was
      70.7% (116/164). It was found that 26% (43/164) of the patients had severe
      malnutrition. Out of this group, 26/43 (60.47%) were < 5 mm reactive to the
      tuberculin test. On the other hand, out of the 91 patients with tuberculin test <
      5 mm, 29% (26/ 91) had severe malnutrition. The use of the score gave the
      following distribution: a) TB very likely in 81.7% (134/164) of the patients; b)
      possible TB in 15.9% (26/164) and TB unlikely in 2.4% (4/164). Among patients who
      had been vaccinated more than 2 years before, there was a 9 times higher risk of
      finding a tuberculin test above 10 mm in individuals with probable TB in
      comparison with the patients with possible or unlikely TB.

PMID- 15565262
TI  - What is the probability of a patient presenting a pleural effusion due to
      tuberculosis?
AB  - INTRODUCTION: In Rio de Janeiro, in almost half of the cases of pleural
      tuberculosis (PT) treatment begins without substantiation of diagnosis. We
      examined variables associated with this disease. METHOD: We studied 215
      consecutive patients; 104 had tuberculosis (TB) and 111 did not (NTB): 41
      neoplasms, 29 transudates, 28 para-pneumonic and 13 other etiologies. Clinical
      and laboratory variables were assessed in a combined manner using likelihood
      ratios (LR) and Bayes' theorem to determine the probability of PT. RESULTS: Among
      the variables examined, adenosine deaminase (ADA) levels, lymphocyte cell
      percentage, protein and age were the best indicators for the diagnosis of PT.
      Association of ADA with any of the other variables led to a LR+ higher than 10
      and a LR- lower than 0.1, indicating the presence or absence of PT, with an
      individual probability of more than 90% or of less than 10% considering that
      there was a 50% initial probability associated with the presence of PT.
      CONCLUSIONS: Since ADA is highly sensitive, we can practically exclude TB as the
      cause of effusion when there are low ADA values. However, to confirm the
      possibility of TB we recommend that other variables, such as prevalence of
      lymphocytes (higher than 90%), and high protein levels (more than 4 g/dL); low
      age (less than 45 years) also should be considered.

PMID- 15565263
TI  - A study of risk factors associated with the prevalence of Cryptosporidium in
      villages around Lake Atitlan, Guatemala.
AB  - Cryptosporidium parvum is an endemic, zoonotic coccidian parasitosis that is
      highly prevalent in third-world countries where waterborne fecal contamination of
      food and drink or person-to-person contact with oocysts are the most common
      methods of transmission of the enteric protozoan. This type of transmission of
      the parasite made the villages around Lake Atitlan, Guatemala a unique site to
      compare environmental risk factors with the level of Cryptosporidium infections
      in the local residents. The study was carried out in two villages, San Antonio
      Palopo and Santa Catarina Palopo, located in the highlands above the shores of
      the lake. Smears from stool specimens of patients with gastroenteritis were
      processed using Kinyoun's modified acid-fast stain and observed with light
      microscopy. Of the 100 residents examined from the two villages, 32% had
      Cryptosporidium infections. Female children had the highest prevalence of
      infection (44% in San Antonio Palopo and 46% in Santa Catarina Palopo, p<0.05),
      and they also had significantly higher infection rates than males, 50% vs. 17%,
      respectively. The prevalence rate was not influenced by the season of the year or
      by the location of the residents. We found differences in prevalence rates due to
      age and gender, and we suggest that the high infection rates of specific groups
      are associated with their exposure to the contaminated water supply from Lake
      Atitlan.

PMID- 15565264
TI  - Cough and fear of sleep: early clinical signs of Bordetella pertussis in an
      adult.
AB  - Pertussis is increasing in frequency among adults, but early diagnosis requires
      special attention to details in the medical history. We describe a 64 year-old
      male with classic signs and symptoms of pertussis and documented Bordetella
      pertussis infection that were overlooked because he presented with a chief
      complaint of cough and fear of falling asleep. Coughing paroxysms and a feeling
      of suffocation (30-60 seconds) only occurred at night after short periods of deep
      sleep (30-45 minutes). The physicians did not observe these episodes during
      daytime examinations, and the basis of the patient's fear of sleep was not
      explored. We recommend reassessment of how adults describe symptoms of pertussis,
      including fear of sleep, and we suggest the use of PCR technology to allow early
      diagnosis and prompt treatment.

PMID- 15565265
TI  - Deficiency of the eighth component of complement associated with recurrent
      meningococcal meningitis--case report and literature review.
AB  - The authors report a case of deficiency of the eighth component of complement in
      a young adult with a history of three episodes of meningitis; one of them proved
      to be meningococcal. The literature was reviewed and meningitis due to Neisseria
      meningitidis strains causing disease in complement-deficient and complement
      sufficient patients was demonstrated. Meningococcal disease may be the first
      manifestation of complement deficiency; screening for complement function must be
      considered for those with invasive meningococcal disease, with posterior
      evaluation of the components of the terminal pathway of complement.

PMID- 15565266
TI  - Pulmonary valve atresia with intact ventricular septum and severe aortic
      stenosis.

PMID- 15565267
TI  - Anomalies of systemic venous return: right superior vena cava draining to the
      left atrium.

PMID- 15565268
TI  - Isolated persistent fifth aortic arch in a patient with Cornelia de Lange
      syndrome.

PMID- 15565269
TI  - An isolated left common carotid artery from the main pulmonary artery: possible
      malseptation of the truncoaortic sac.
AB  - An isolated left common carotid artery (LCA) is an extremely rare condition with
      only four reported cases. In each case, the isolated carotid artery connects to
      the right or left pulmonary artery via the ductus arteriosus and the embryologic
      basis for the abnormalities is believed to reflect an error in the development of
      the branchial arches. We present a case of an isolated LCA connecting to the main
      pulmonary artery in association with a right aortic arch and an anomalous origin
      of the left subclavian artery from the descending aorta. The left ligamentus
      arteriosus was identified separately. This may represent a disturbance in the
      septation of the truncoaortic sac secondary to abnormal migration of neural crest
      cells rather than a pure developmental anomaly of the branchial arches.

PMID- 15565270
TI  - Hypoplastic left heart syndrome and valvar pulmonary stenosis: presentation and
      management.
AB  - We describe the first report of an infant who was born with hypoplastic left
      heart syndrome and significant pulmonary stenosis. He was successfully palliated
      with multiple cardiac catheterization interventions while waiting for cardiac
      transplantation. This unusual constellation of heart defects is an entity that is
      rare and not well described in the literature.

PMID- 15565271
TI  - Myocardial infarction late after Mustard procedure.
AB  - This case report discusses a young man with d-transposition of the great arteries
      who suffered three myocardial infarctions late after his Mustard procedure. The
      etiology was found to be a coronary embolism, with a mural thrombus in the
      systemic ventricle as the probable nidus. The risk factors of coronary embolism
      are discussed, and it is concluded that Mustard patients are at risk for coronary
      embolization and myocardial infarction, which can be a cause of sudden death.

PMID- 15565272
TI  - Complementary DNA cloning and molecular evolution of opine dehydrogenases in some
      marine invertebrates.
AB  - The complete complementary DNA sequences of genes presumably coding for opine
      dehydrogenases from Arabella iricolor (sandworm), Haliotis discus hannai
      (abalone), and Patinopecten yessoensis (scallop) were determined, and partial
      cDNA sequences were derived for Meretrix lusoria (Japanese hard clam) and Spisula
      sachalinensis (Sakhalin surf clam). The primers ODH-9F and ODH-11R proved useful
      for amplifying the sequences for opine dehydrogenases from the 4 mollusk species
      investigated in this study. The sequence of the sandworm was obtained using
      primers constructed from the amino acid sequence of tauropine dehydrogenase, the
      main opine dehydrogenase in A. iricolor. The complete cDNA sequence of A.
      iricolor, H. discus hannai, and P. yessoensis encode 397, 400, and 405 amino
      acids, respectively. All sequences were aligned and compared with published
      databank sequences of Loligo opalescens, Loligo vulgaris (squid), Sepia
      officinalis (cuttlefish), and Pecten maximus (scallop). As expected, a high level
      of homology was observed for the cDNA from closely related species, such as for
      cephalopods or scallops, whereas cDNA from the other species showed lower-level
      homologies. A similar trend was observed when the deduced amino acid sequences
      were compared. Furthermore, alignment of these sequences revealed some structural
      motifs that are possibly related to the binding sites of the substrates. The
      phylogenetic trees derived from the nucleotide and amino acid sequences were
      consistent with the classification of species resulting from classical taxonomic
      analyses.

PMID- 15565273
TI  - An extended aqueous solvation model based on atom-weighted solvent accessible
      surface areas: SAWSA v2.0 model.
AB  - A new method is proposed for calculating aqueous solvation free energy based on
      atom-weighted solvent accessible surface areas. The method, SAWSA v2.0, gives the
      aqueous solvation free energy by summing the contributions of component atoms and
      a correction factor. We applied two different sets of atom typing rules and
      fitting processes for small organic molecules and proteins, respectively. For
      small organic molecules, the model classified the atoms in organic molecules into
      65 basic types and additionally. For small organic molecules we proposed a
      correction factor of "hydrophobic carbon" to account for the aggregation of
      hydrocarbons and compounds with long hydrophobic aliphatic chains. The
      contributions for each atom type and correction factor were derived by
      multivariate regression analysis of 379 neutral molecules and 39 ions with known
      experimental aqueous solvation free energies. Based on the new atom typing rules,
      the correlation coefficient (r) for fitting the whole neutral organic molecules
      is 0.984, and the absolute mean error is 0.40 kcal mol(-1), which is much better
      than those of the model proposed by Wang et al. and the SAWSA model previously
      proposed by us. Furthermore, the SAWSA v2.0 model was compared with the simple
      atom-additive model based on the number of atom types (NA). The calculated
      results show that for small organic molecules, the predictions from the SAWSA
      v2.0 model are slightly better than those from the atom-additive model based on
      NA. However, for macromolecules such as proteins, due to the connection between
      their molecular conformation and their molecular surface area, the atom-additive
      model based on the number of atom types has little predictive power. In order to
      investigate the predictive power of our model, a systematic comparison was
      performed on seven solvation models including SAWSA v2.0, GB/SA_1, GB/SA_2,
      PB/SA_1, PB/SA_2, AM1/SM5.2R and SM5.0R. The results showed that for organic
      molecules the SAWSA v2.0 model is better than the other six solvation models. For
      proteins, the model classified the atoms into 20 basic types and the predicted
      aqueous free energies of solvation by PB/SA were used for fitting. The solvation
      model based on the new parameters was employed to predict the solvation free
      energies of 38 proteins. The predicted values from our model were in good
      agreement with those from the PB/SA model and were much better than those given
      by the other four models developed for proteins.

PMID- 15565274
TI  - Effects of arbuscular mycorrhizal colonization and phosphorus application on
      nuclear ploidy in Allium porrum plants.
AB  - Arbuscular mycorrhizal (AM) colonization can strongly affect the plant cell
      nucleus, causing displacement from the periphery to the center of the cell,
      hypertrophy and polyploidization. The hypertrophy response has been shown in a
      variety of AM plants whilst polyploidization has been reported only in
      Lycopersicon esculentum, a multiploid species with a small genome. In order to
      determine whether polyploidization is a general plant response to AM
      colonization, analyses were performed on Allium porrum, a plant with a large
      genome, which is much less subject to polyploidization than L. esculentum. The
      ploidy status of leaves, complete root systems and four zones of the adventitious
      roots was investigated in relation to phosphorus content, AM colonization and
      root differentiation in A. porrum plants grown under two different regimes of
      phosphate nutrition in order to distinguish direct effects of the fungus from
      those of improved nutrition. Results showed the presence of two nuclear
      populations (2C and 4C) in all treatments and samples. Linear regression analyses
      suggested a general negative correlation between phosphorus content and the
      proportion of 2C nuclei. The percentage of 2C nuclei (and consequently that of 4C
      nuclei), was also influenced by AM colonization, differentiation and ageing of
      the root cells, which resulted in earlier occurrence, in time and space, of
      polyploid nuclei.

PMID- 15565275
TI  - Quality of life in long-term childhood cancer survivors and the relation of late
      effects and subjective well-being.
AB  - GOALS: The purpose of the present study was the assessment of health-related
      quality of life in adult long-term survivors of childhood cancer and the
      detection of possible treatment- and cancer-related late effects. The relation of
      objective medical data and subjective appraisal was also examined by combining
      the doctor's and the patient's views of the perceived health status. PATIENTS AND
      METHODS: Seventy-eight young adults at the age of at least 18 years who had been
      diagnosed with cancer in the years 1975-1995 and were off therapy at least 5
      years with no evidence of disease participated. Cancer survivors completed self
      rating instruments [SF-36 Health Survey, Nottingham Health Profile (NHP), Beck's
      Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) trait-anxiety
      scale]; the doctor assessed the patient's health by means of the Common Toxicity
      Criteria (CTCv2). MAIN RESULTS: The cancer survivors showed a mostly higher-than
      average positive subjective rating of the various areas of quality of life. In
      comparison to the general population, the cancer survivors showed lower extents
      of depression. In 64.1% of the cancer survivors, medical rating and self
      assessment regarding the perceived health status corresponded. Cancer survivors
      who felt severely impaired regarding their subjectively perceived well-being
      showed worse results in some dimensions of quality of life than persons who
      subjectively felt mildly impaired. The so-called "unfortunate" persons showed the
      worst assessment of quality of life and the highest extent of depression and
      anxiety. CONCLUSIONS: The results of the present study may be helpful in planning
      an appropriate multidisciplinary, long-term follow-up of childhood cancer
      survivors.

PMID- 15565276
TI  - Acute emesis: moderately emetogenic chemotherapy.
AB  - This paper is a review of the recommendations for the prophylaxis of acute emesis
      induced by moderately emetogenic chemotherapy as concluded at the Perugia
      Consensus Conference, which took place at the end of March 2004. The review
      focuses on new studies appearing since the last consensus conference in 1997. The
      following issues are addressed: dose and schedule of antiemetics, different
      groups of antiemetics such as corticosteroids, serotonin (5-HT(3))-receptor
      antagonists, dopamine D(2) receptor antagonists, and neurokinin (NK(1)) receptor
      antagonists. Antiemetic prophylaxis in patients receiving multiple cycles of
      moderately emetogenic chemotherapy is also reviewed. Consensus statements are
      given, including optimal dose and schedule of 5-HT(3)-receptor antagonists and of
      dexamethasone. The new 5-HT(3)-receptor antagonist, palonosetron, is a reasonable
      alternative to the well-established agents of this class--ondansetron,
      granisetron, tropisetron and dolasetron. It is concluded that the best
      prophylaxis in patients receiving moderately emetogenic chemotherapy is still the
      combination of one of the 5-HT(3)-receptor antagonists and dexamethasone. The
      results of studies adding a NK(1)-receptor antagonist to this combination are
      awaited and might change future recommendations.

PMID- 15565277
TI  - Consensus proposals for the prevention of acute and delayed vomiting and nausea
      following high-emetic-risk chemotherapy.
AB  - This paper uses an evidence-based approach whenever possible to formulate
      recommendations, emphasizing the results of controlled trials concerning the best
      use of antiemetic agents. We address issues of dose, schedule, and route of
      administration of five selective 5-HT(3) antagonists. We conclude that for each
      of these five drugs, there is a plateau in therapeutic efficacy above which
      further dose escalation does not improve outcome. Furthermore, for all classes of
      antiemetic agents, a single dose is as effective as multiple doses or a
      continuous infusion. The oral route is as efficacious as the intravenous route of
      administration, even with chemotherapy of high emetic risk. Selective antagonists
      of the type 3 serotonin receptor (5-HT(3)) in combination with dexamethasone and
      aprepitant are the standard of care for the prevention of emesis following
      chemotherapy of high emetic risk.

PMID- 15565278
TI  - Climate variability and campylobacter infection: an international study.
AB  - Campylobacter is among the most important agents of enteritis in developed
      countries. We have described the potential environmental determinants of the
      seasonal pattern of infection with campylobacter in Europe, Canada, Australia and
      New Zealand. Specifically, we investigated the role of climate variability on
      laboratory-confirmed cases of campylobacter infection from 15 populations.
      Regression analysis was used to quantify the associations between timing of
      seasonal peaks in infection in space and time. The short-term association between
      weekly weather and cases was also investigated using Poisson regression adapted
      for time series data. All countries in our study showed a distinct seasonality in
      campylobacter transmission, with many, but not all, populations showing a peak in
      spring. Countries with milder winters have peaks of infection earlier in the
      year. The timing of the peak of infection is weakly associated with high
      temperatures 3 months previously. Weekly variation in campylobacter infection in
      one region of the UK appeared to be little affected by short-term changes in
      weather patterns. The geographical variation in the timing of the seasonal peak
      suggests that climate may be a contributing factor to campylobacter transmission.
      The main driver of seasonality of campylobacter remains elusive and underscores
      the need to identify the major serotypes and routes of transmission for this
      disease.

PMID- 15565279
TI  - Sleep disturbances in pediatric dialysis patients.
AB  - Sleep disorders are common in adult dialysis patients, with a prevalence of 60%
      80%. To date, sleep disturbances have not been assessed in the pediatric dialysis
      population. Therefore, the objective of this study is to describe the prevalence
      of sleep disturbance symptoms in a pediatric dialysis population. We conducted a
      telephone- or clinic-based interview of 21 children (aged 6-20 years) and their
      parents in our academic tertiary pediatric dialysis center with questionnaires
      that assessed four symptom domains of sleep disorders: (1) sleep-disordered
      breathing, (2) restless leg syndrome or period limb movements (RLS/PLMs), (3)
      excessive daytime sleepiness, and (4) inadequate sleep time. The presence of a
      "sleep disturbance" was defined by positive responses in any of the four symptom
      domains. Overall, 18 (86%) of the children undergoing dialysis [mean age (SD)
      14.2 years (1.1), gender (M/F) 11/10] endorsed sleep disturbance symptoms: sleep
      disordered breathing (46%), RLS/PLMs (29%), and excessive daytime sleepiness
      (60%). We conclude that sleep disturbances are very common in pediatric dialysis
      patients, but may be underrecognized. Given the adverse neurocognitive and
      physiological outcomes associated with poor sleep, it is important for
      practitioners caring for children on dialysis to anticipate and screen for
      treatable sleep conditions.

PMID- 15565280
TI  - Announcing transfer of editorship.

PMID- 15565281
TI  - High-rate thermophilic methane fermentation on short-chain fatty acids in a down
      flow anaerobic packed-bed reactor.
AB  - In order to maximize the efficiency of methane fermentation on short-chain fatty
      acids, growth media containing acetic acid and butyric acid as major carbon
      sources were supplied to a thermophilic down-flow anaerobic packed-bed reactor.
      The organic loading rate (OLR) to the reactor ranged from 0.2 to 169 kg
      dichromate chemical oxygen demand(CODcr)/m(3)-reactor/day, corresponding to a
      hydraulic retention time (HRT) of between 1.4 h and 20 days. Stable methane
      production was maintained at HRTs as short as 2 h (OLR=120 kg-CODcr/m(3)/day),
      with the short-chain fatty acids in the feed almost completely removed during the
      process. The apparent substrate removal efficiency, determined from the total
      CODcr values in the influent and effluent, was 75% at short HRTs. However, the
      actual substrate removal efficiency must have been greater than 75%, since a
      fraction of substrate was also utilized in microbial cell synthesis, and these
      cells were part of the measured total CODcr.

PMID- 15565282
TI  - Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader
      Willi syndrome.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurogenetic
      disorders caused by the loss of function of imprinted genes in 15q11-q13. The
      maternally expressed UBE3A gene is affected in AS. Four protein-encoding genes
      (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and several small nucleolar (sno) RNA genes
      (HBII-13, HBII-436, HBII-85, HBII-438A, HBII-438B and HBII-52) are expressed from
      the paternal chromosome only but their contribution to PWS is unclear. To examine
      the role of the HBII-52 snoRNA genes, we have reinvestigated an AS family with a
      submicroscopic deletion spanning UBE3A and flanking sequences. By fine mapping of
      the centromeric deletion breakpoint in this family, we have found that the
      deletion affects all of the 47 HBII-52 genes. Since the complete loss of the HBII
      52 genes in family members who carry the deletion on their paternal chromosome is
      not associated with an obvious clinical phenotype, we conclude that HBII-52
      snoRNA genes do not play a major role in PWS. However, we cannot exclude the
      possibility that the loss of HBII-52 has a phenotypic effect when accompanied by
      the loss of function of other genes in 15q11-q13.

PMID- 15565283
TI  - Small heat-shock protein 22 mutated in autosomal dominant Charcot-Marie-Tooth
      disease type 2L.
AB  - Charcot-Marie-Tooth (CMT) disease is the most common inherited motor and sensory
      neuropathy. We have previously described a large Chinese CMT family and assigned
      the locus underlying the disease (CMT2L; OMIM 608673) to chromosome 12q24. Here,
      we report a novel c.423G-->T (Lys141Asn) missense mutation of small heat-shock
      protein 22-kDa protein 8 (encoded by HSPB8), which is also responsible for distal
      hereditary motor neuropathy type (dHMN) II. No disease-causing mutations have
      been identified in another 114 CMT families.

PMID- 15565284
TI  - Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes.
AB  - The ATP-sensitive potassium (KATP) channel couples membrane excitability to
      cellular metabolism and is a critical mediator in the process of glucose
      stimulated insulin secretion. Increasing numbers of KATP channel polymorphisms
      are being described and linked to altered insulin secretion indicating that genes
      encoding this ion channel could be susceptibility markers for type-2 diabetes.
      Genetic variation of KATP channels may result in altered beta-cell electrical
      activity, glucose homeostasis, and increased susceptibility to type-2 diabetes.
      Of particular interest is the Kir6.2 E23K polymorphism, which is linked to
      increased susceptibility to type-2 diabetes in Caucasian populations and may also
      be associated with weight gain and obesity, both of which are major diabetes risk
      factors. This association highlights the potential contribution of both genetic
      and environmental factors to the development and progression of type-2 diabetes.
      In addition, the common occurrence of the E23K polymorphism in Caucasian
      populations may have conferred an evolutionary advantage to our ancestors. This
      review will summarize the current status of the association of KATP channel
      polymorphisms with type-2 diabetes, focusing on the possible mechanisms by which
      these polymorphisms alter glucose homeostasis and offering insights into possible
      evolutionary pressures that may have contributed to the high prevalence of KATP
      channel polymorphisms in the Caucasian population.

PMID- 15565285
TI  - Meningococccal meningitis and complement component 6 deficiency associated with
      oculocutaneous albinism.

PMID- 15565286
TI  - Presenting phenotype in 100 children with the 22q11 deletion syndrome.
AB  - The aim of this study was to investigate and describe the presenting phenotype of
      children with the 22q11 deletion syndrome and to describe common clinical
      features that could serve as guidelines in the clinical diagnostic process
      preceding genetic testing. A hospital-based study of 100 consecutive children and
      adolescents with 22q11 deletion was initiated. The patients were divided into two
      groups according to age at diagnosis: before or after 2 years of age. Clinical
      features were grouped into a core set of eight features: cardiac defects, non
      visible/hypoplastic thymus or infection problems, hypocalcaemia, feeding
      difficulties, cleft palate/speech-language impairment, developmental
      delay/learning difficulties, characteristic dysmorphic features and other
      malformations and deformities. The median age at diagnosis was 6.7 years. Of all
      patients, 26% were diagnosed in infancy and 92% had a congenital cardiac defect,
      whereas 54% of those diagnosed later had a cardiac defect. A cleft palate was
      present in 25 cases and 44 had some other malformation or deformity. All
      presented with a combination of many of the core features. Of those diagnosed
      after 2 years of age, the majority presented with speech-language impairment,
      developmental delay or learning difficulties and recurrent infections.
      Characteristic mild dysmorphic features were noticed in all children. CONCLUSION:
      In spite of variable clinical expression, children with 22q11 deletion share a
      number of major features and have a characteristic phenotype. A high proportion
      have no cardiac defect and hence a risk of diagnostic delay. Increased awareness
      and knowledge among general paediatricians and other specialists who meet these
      children early in life is needed to reduce the diagnostic delay.

PMID- 15565288
TI  - AtSTP11, a pollen tube-specific monosaccharide transporter in Arabidopsis.
AB  - Pollen development, as well as pollen germination and pollen tube growth,
      requires a highly regulated supply of sugars. In this paper we describe the
      molecular, kinetic, and physiological characterization of AtSTP11, a new member
      of the H+/monosaccharide transporter family in Arabidopsis thaliana (L.) Heynh.
      Heterologous expression in yeast (Saccharomyces cerevisiae) showed that AtSTP11
      is a high-affinity (Km = 25 microM), broad-spectrum, and uncoupler-sensitive
      monosaccharide transporter of the plasma membrane. In reverse transcription
      polymerase chain reaction analyses we found that AtSTP11 expression is restricted
      to flowers. Furthermore, AtSTP11-promoter::GFP plants revealed that AtSTP11
      expression is only found in pollen tubes. Using a specific antibody we could also
      detect the AtSTP11 protein exclusively in pollen tubes but not in other flower
      tissues or in pollen grains of any developmental stage. These results suggest
      that the newly identified AtSTP11 transporter plays a role in the supply of
      monosaccharides to growing pollen tubes.

PMID- 15565289
TI  - Surface morphology and chemistry of Prunus laurocerasus L. leaves: a study using
      X-ray photoelectron spectroscopy, time-of-flight secondary-ion mass spectrometry,
      atomic-force microscopy and scanning-electron microscopy.
AB  - The surface properties of the plant cuticle play a crucial role in plant-pathogen
      interactions and the retention and penetration of agriculturally important
      chemicals. This paper describes the use of X-ray photoelectron spectroscopy
      (XPS), time-of-flight secondary-ion mass spectrometry (ToF-SIMS), tapping-mode
      atomic force microscopy (TM-AFM) and scanning electron microscopy (SEM) to
      determine surface-specific chemical and material properties of the adaxial
      surface of Prunus laurocerasus L. leaves. XPS data, derived from the uppermost
      few nanometres (< 10 nm) of the leaf surface, were consistent with the wax
      components and functionality known to be present within the waxes. ToF-SIMS
      provided molecular speciation from the outermost monolayer of the leaf surface,
      indicating the importance of a family of acetates with chain lengths ranging from
      C20 to C34. The presence of alkanes with C29 and C31 chain lengths was also
      confirmed. SEM and TM-AFM topography images revealed a textured granular surface,
      while simultaneously recorded AFM phase images revealed heterogeneous material
      properties at the nanoscale. The relevance of these data to plant cuticle
      development, allelochemistry and agrochemical delivery is discussed.

PMID- 15565291
TI  - The VO2 response for an exhaustive treadmill run at 800-m pace: a breath-by
      breath analysis.
AB  - Recent research in which data were averaged over 10 or 30 s suggests that the
      VO(2) response of aerobically fit individuals plateaus below VO(2 max) in an
      exhaustive square-wave run lasting approximately 2 min. To investigate this
      phenomenon we examined the breath-by-breath VO(2) response of trained runners to
      an exhaustive treadmill run at 800 m pace. Eight male competitive runners
      completed two treadmill tests on separate days: a ramp test to exhaustion and an
      exhaustive square-wave run at 800-m pace. For the ramp test, the breath-by-breath
      data were smoothed with a 15-s moving average and the highest of the smoothed
      values was taken as VO(2 peak) [mean (SD): 68.9 (5.6) ml kg(-1) min(-1)]. For the
      square-wave, the breath-by-breath data were interpolated to give one value per
      second and modelled using a monoexponential function. Following a delay of 11.2
      (1.5) s, VO(2) increased quickly [phase-2 time constant of 10.7 (2.7) s] towards
      an asymptote that represented just 85 (6)% of VO(2 peak) from the ramp test.
      Expressed in ml kg(-1) min(-1), this asymptote was independent of VO(2 peak)
      (r=0.04, P=0.94). However, as a percentage of VO(2 peak) it was negatively
      correlated with VO(2 peak) itself (r=-0.96, P<0.001). It is concluded that in an
      exhaustive square-wave treadmill run lasting approximately 2 min the VO(2) of
      aerobically fit runners increases quickly to plateau at a level that is lower
      than, but independent of, VO(2max).

PMID- 15565292
TI  - Can the injection of the patient's own bone marrow-derived stem cells preserve
      cone vision in retinitis pigmentosa and other diseases of the eye?

PMID- 15565293
TI  - Optical coherence tomography can measure axonal loss in patients with ethambutol
      induced optic neuropathy.
AB  - PURPOSE: To map and identify the pattern, in vivo, of axonal degeneration in
      ethambutol-induced optic neuropathy using optical coherence tomography (OCT).
      Ethambutol is an antimycobacterial agent often used to treat tuberculosis. A
      serious complication of ethambutol is an optic neuropathy that impairs visual
      acuity, contrast sensitivity, and color vision. However, early on, when the toxic
      optic neuropathy is mild and partly reversible, the funduscopic findings are
      often subtle and easy to miss. METHODS: Three subjects with a history of
      ethambutol (EMB)-induced optic neuropathy of short-, intermediate-, and long-term
      visual deficits were administered a full neuro-ophthalmologic examination
      including visual acuity, color vision, contrast sensitivity, and fundus
      examination. In addition, OCT (OCT 3000, Humphrey-Zeiss, Dublin, CA) was
      performed on both eyes of each subject using the retinal nerve fiber layer (RNFL)
      analysis protocol. OCT interpolates data from 100 points around the optic nerve
      to effectively map out the RNFL. RESULTS: The results were compared to the
      calculated average RNFL of normal eyes accumulated from four prior studies using
      OCT, n=661. In all subjects with history of EMB-induced optic neuropathy, there
      was a mean loss of 72% nerve fiber layer thickness in the temporal quadrant
      (patient A, with eventual recovery of visual acuity and fields, 58% loss; patient
      B, with intermediate visual deficits, 68% loss; patient C, with chronic visual
      deficits, 90% loss), with an average mean optic nerve thickness of 26+/-16
      microm. There was a combined mean loss of 46% of fibers from the superior,
      inferior, and nasal quadrants in the (six) eyes of all three subjects (mean
      average thickness of 55+/-29 microm). In both sets (four) of eyes of the subjects
      with persistent visual deficits (patients B and C), there was an average loss of
      79% of nerve fiber thickness in the temporal quadrant. CONCLUSIONS: The OCT
      results in these patients with EMB-induced optic neuropathy show considerable
      loss especially of the temporal fibers. This is consistent with prior
      histopathological studies that show predominant loss of parvo-cellular axons (or
      small-caliber axons) within the papillo-macular bundle in toxic or hereditary
      optic neuropathies. OCT can be a valuable tool in the quantitative analysis of
      optic neuropathies. Additionally, in terms of management of EMB-induced optic
      neuropathy, it is important to properly manage ethambutol dosing in patients with
      renal impairment and to achieve proper transition to a maintenance dose once an
      appropriate loading dose has been reached.

PMID- 15565294
TI  - Longitudinal and cross-sectional study of patients with early-onset severe
      retinal dystrophy associated with RPE65 mutations.
AB  - PURPOSE: To quantify retinal function longitudinally and cross-sectionally in
      patients with autosomal-recessive early-onset severe retinal dystrophy (EOSRD)
      associated with RPE65 mutations. SUBJECTS AND METHODS: The ocular phenotype was
      characterized in four children from three families up to the second decade of
      life, and in three siblings from one family aged 43-54 years carrying compound
      heterozygous or homozygous mutations in RPE65. Standard clinical examination
      included colour vision testing, fundus photography and Goldmann visual fields
      (GVF). Full-field ERGs (in all) and multifocal ERGs (in two patients) were also
      recorded. Visual performance and fundus appearance were compared to literature
      data. RESULTS: In childhood, visual acuity (VA) ranged from 0.1 to 0.3, and GVF
      for target V4 was well preserved. VA and GVF were measurable in only one of the
      three adult siblings. Nystagmus was present in two of four children and two of
      three adults. Photophobia was absent in childhood and developed in adulthood.
      Funduscopic changes were discrete during the first decade of life in three of
      four children; one patient had clear macular changes already at age 5 years. All
      three adult siblings had distinct retinal changes including the macula. Bone
      spicules were not a feature. Residual colour vision was present in all patients
      with measurable VA. Rod ERGs were absent at any age; cone ERGs were detectable in
      early childhood. To date, VA data have been reported in 51 patients, visual
      fields in 29 patients, and a detailed fundus description in 34 patients. For all
      three parameters, data were comparable to the results in our patient cohort.
      CONCLUSION: In childhood, patients with RPE65 mutations have better visual
      functions than typically seen in Leber congenital amaurosis. The phenotype shows
      a common progressive pattern with intrafamilial and interfamilial variation. The
      data suggest a preserved retinal morphology at young ages, arguing for vision
      restoring gene therapy trials in childhood.

PMID- 15565295
TI  - The Fang population of Equatorial Guinea characterised by 15 STR-PCR
      polymorphisms.
AB  - Allele frequencies for 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D19S433,
      HUMVWA31A, HUMTPOX, D18S51, D3S1358, HUMTHO1, D13S317, D16S539, D2S1338, D5S818
      and HUMFGA) were analysed in the Fang population of Bioko Island, Equatorial
      Guinea. No deviation from Hardy-Weinberg equilibrium was found for all loci.
      Statistical parameters demonstrated the forensic utility of the analysed systems.

PMID- 15565296
TI  - Population and mutation analysis of 17 Y-STR loci from Rio de Janeiro (Brazil).
AB  - The 17 Y chromosome STR loci DYS19, DYS385, DYS389I and II, DYS390, DYS391,
      DYS392, DYS393, DYS437, DYS438, DYS439, DYS460, DYS461, GATA C4, GATA H4 and GATA
      A10 were analyzed in a male sample of 126 unrelated individuals from Rio de
      Janeiro. No shared haplotypes were observed, demonstrating the usefulness and
      informative power of these Y-STRs in male lineage identification in Rio de
      Janeiro. Pairwise haplotype analysis showed no significant differences in the
      comparison of Rio de Janeiro with Iberian samples from different regions of
      Portugal and Spain, as well as with other Caucasian samples from South America,
      namely Costa Rica, Buenos Aires (Argentina) and Sao Paulo (Brazil). The same set
      of Y-STRs was also typed in 119 father/son pairs and among 2,023 allele
      transfers, 8 mutations were observed with an overall mutation rate of 0.003955+/
      0.001396 per locus/meiosis across the 17 loci. Except in one case, all mutations
      were single step. For DYS438 a four-step mutation was found which has never been
      reported before, where allele 10 mutated to allele 6.

PMID- 15565297
TI  - Y-STR analysis for detection and objective confirmation of child sexual abuse.
AB  - We evaluated 26 child sexual assault cases for the incorporation of Y-STR
      screening in the routine detection and objective confirmation of sexual contact
      between the child victim and the perpetrator. Various samples, e.g. vaginal or
      anal swabs from patients aged 2-17 years old (25 females, 1 male), were collected
      6-72 h after the incident. Due to the limited amounts of DNA in these samples,
      total DNA was extracted using a one-step procedure and screened with autosomal
      STRs to detect signs of a victim-assailant DNA mixture and with Y-STRs for
      assailant DNA. Autosomal STRs failed to give signs of victim-assailant DNA
      mixtures while Y-STRs were detected in 24 of the 26 cases corresponding to a
      success rate of 92.3%. With the possible presence of both male sperm and/or male
      epithelial cells in forensic evidence, Y-STR DNA markers were detected regardless
      of external ejaculation, microscopic detection of sperm and with post-coital
      intervals of up to 72 h. While only partial profiles were generated owing to low
      quantities of male DNA present, Y-STR screening results can serve as objective
      evidence of sexual contact in child sexual abuse cases involving victims who do
      not have any previous sexual history. This type of evidence can corroborate child
      victim testimony and spare the child victim from further trauma caused by
      prolonged forensic investigations and court proceedings. Alternatively, Y-STR
      screening can provide objective proof of non-involvement of an accused with the
      victim.

PMID- 15565298
TI  - Pattern of interleukin-6 receptor complex immunoreactivity between cortical
      regions of rapid autopsy normal and Alzheimer's disease brain.
AB  - Involvement of the interleukin-6 receptor complex (IL-6RC) in neuroregulatory and
      immunological processes of the brain and particularly in Alzheimer's disease (AD)
      has been hypothesized. The functionally active IL-6RC consists of the cytokine IL
      6, which acts through the ligand binding IL-6R and the signal transducing gp130.
      Using a new immunocytochemical protocol on rapid autopsy cryostat brain sections
      we studied the expression of the IL-6RC in Braak IV-V staged AD patients compared
      to normal age-matched controls (HC) across five different cortical regions. Inter
      rater reliability of the method was high. The "baseline" expression in normal
      human brain was determined for IL-6,IL-6R and gp130 in all cortical regions. In
      normal tissue IL-6 expression was lower in parietal cortex. Higher IL-6R
      expression was shown in frontal, occipital and parietal cortex, lower expression
      in temporal cortex and cerebellum. In AD IL-6 expression levels were generally
      increased in parietal cortex and decreased in occipital cortex compared to
      controls. IL-6R expression levels were strongly increased in AD frontal and
      occipital cortex and decreased in temporal cortex and cerebellum. Our findings
      indicate an altered cortical immunoreactivity pattern of the functional IL-6RC in
      AD supporting the hypothesis of a disease-related role of IL-6 in AD
      pathophysiology.

PMID- 15565299
TI  - Risperidone plasma levels, clinical response and side-effects.
AB  - INTRODUCTION: Assessment of the relation between oral risperidone dose, serum
      drug levels and clinical response may provide important information for rational
      treatment decisions. Inter-individual differences in the liver cytochrome P450
      system, especially in the CYP2D6 subsystem, which account for a significant
      portion of risperidone metabolism, may also influence plasma drug levels and
      alter clinical response parameters. We thus prospectively investigated
      risperidone serum concentrations in relation to clinical efficacy and side
      effects and genotyped major CYP2D6 polymorphisms to determine their effect upon
      these parameters. METHODS: Neuroleptic monotherapy with risperidone was
      administered to schizophrenia patients in a 6-week open dose clinical trial.
      Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS
      to assess medication side effects; and blood draws to quantify steady state
      plasma levels of risperidone and 9-OH-risperidone were carried out. In addition,
      major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped.
      RESULTS: Eighty-two patients were recruited. Mean oral dose of risperidone was
      4.3 +/- 0.9 mg. Mean plasma level of both risperidone and 9-OH-risperidone
      together ("active moiety") was 41.6 +/- 26.6 ng/ml. Significant improvements in
      PANSS scales and the various subscales ensued. There was a positive linear
      correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015)
      and between risperidone and 9-OH-risperidone levels (r = 0.262; p = 0.016).
      Nonresponders to pharmacotherapy (PANSS-Improvement < 30%) showed significantly
      higher active moiety plasma levels (49.9 +/- 30.7 ng/ml) than responders (38.2 +/
      17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601).
      Patients with longer illness duration (> or = 3 years) had significantly higher
      plasma drug levels than those with a shorter course (< 3 years; p = 0.039).
      Extrapyramidal side effects (EPS) and plasma levels were not correlated (r =
      0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for
      EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of
      risperidone were significantly more likely to respond with EPS in the trial
      course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4.
      CYP2D6 polymorphisms did not predict clinical response, but predicted a
      tendential increase in the plasma risperidone to 9-OH-risperidone ratio (0.5 +/-
      0.6 vs. 1.9 +/- 1.8; p = 0.120). DISCUSSION: The major finding was that
      responders to risperidone treatment had significantly lower blood levels of
      risperidone and 9-OH risperidone than patients who did not respond to the
      treatment despite administration of similar oral doses. The observed CYP2D6
      polymorphisms did not contribute to altered clinical efficacy, but affected
      risperidone to 9-OH-risperidone ratios. Increased plasma levels of the active
      moiety in patients with longer illness may represent general aging effects.
      Conversely, the observed higher plasma levels in nonresponders may derive from
      unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances.
      Patients initially receiving higher oral risperidone doses were more likely to
      respond with extrapyramidal side effects which reaffirms the need for careful
      titration. The high inter-individual variability in risperidone and 9-OH
      risperidone metabolization and the relationship between clinical outcome and
      plasma levels warrants regular plasma level monitoring of both compounds to
      assess for the clinically relevant active moiety.

PMID- 15565300
TI  - Signs of rapidly progressive dementia in a case of intravascular lymphomatosis.
AB  - Intravascular lymphomatosis (IVL), a rare type of non-Hodgkin's lymphoma, is an
      uncommon cause of progressive dementia, usually followed by death within a few
      months of onset of clinical disease. Often this aggressive tumor is only
      diagnosed at autopsy, because of misleading clinical features mimicking a broad
      spectrum of syndromes and the absence of circulating lympoma cells in the blood,
      bone marrow or cerebrospinal fluid in many cases. Here we present IVL in a 78
      year-old woman with findings leading to the clinical diagnosis of vascular
      dementia with sudden beginning and positive 14-3-3 protein in the CSF, commonly
      reported in Creutzfeldt-Jakob disease (CJD).

PMID- 15565301
TI  - Keratinocyte and dermal vascular endothelial cell capacities remain unimpaired in
      the margin of chronic venous ulcer.
AB  - The role of endogenously produced cytokines and growth factors in the impaired
      healing of chronic leg ulcers remains uncertain. The aim of this study was to
      determine the functional capacity of skin cells in ulcer bed tissue compared to
      those in the edge of ulcers and skin distal to ulcers. Biopsies from leg ulcers
      of ten randomly selected patients were examined immunohistochemically for
      cytokines and growth factors produced by keratinocytes (KC) and vascular
      endothelial cells (EC). The phenotype of leukocytes infiltrating venous ulcers
      and the expression of vascular adhesion molecules responsible for extravasation
      were also studied. The expression of cytokines and growth factors by KC was
      similar in areas adjacent and remote from an ulcer. In the dermis adjacent to an
      ulcer, the expression of IL-1alpha, IL-1beta, IL-1Ra, EGF and PDGFa by EC was
      higher than the levels of expression in EC from the distant dermis. The
      expression of IL-6, TNFalpha and GM-CSF was comparable to that in cells from
      intact dermis. For all these factors staining was cytoplasmic, suggesting
      production in these areas. Ulcer bed tissue contained few fibroblasts and blood
      capillaries showing a high staining intensity for CD62E and CD106 EC adhesion
      molecules but no FGF2 expression (P<0.05). The intensity of staining for
      scavenging CD15+ elastase+ granulocytes and CD35+ (C3bR) activated macrophages in
      the ulcer bed was comparable to that in the margin but higher than that in the
      distant dermis (P<0.05), whereas staining for CD68+, HLA DR+, TGFbeta+ and CD54+
      dermal macrophages was similar in all areas. There was reduced staining for CD4+
      and CD8+ cells in the ulcer bed (P<0.05). There were no CD1a+ Langerhans cells in
      the epidermis encroaching upon the granulation tissue and there was reduced CD1a
      staining in the adjacent epidermis (P<0.05). In conclusion, there is chronic
      accumulation of scavenging cells with lack of remodeling of the granulation
      tissue and, at the same time, preserved cytokine and growth factor secretory
      potential of KC and dermal EC in non-healing venous leg ulcers.

PMID- 15565302
TI  - Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell
      carcinoma syndrome.
AB  - We identified seven novel germline mutations of the PTCH gene in eight unrelated
      Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to
      ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplified
      from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations were
      found in all eight patients with NBCCS. The mutations detected in this study
      include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletions,
      one nonsense mutation and two missense mutations. None of the mutations have been
      previously reported. Five mutations caused premature stop codons that are
      predicted to result in a truncated protein. In the two missense mutations, the
      strong basic residue arginine was substituted by serine or glycine in highly
      conserved components of the putative transmembrane domain of PTCH, and these
      mutations may therefore affect the conformation and function of the PTCH protein.
      No phenotype-genotype relationships were found in the Japanese NBCCS patients,
      consistent with results of previous studies on NBCCS in African-American and
      Caucasian patients.

PMID- 15565303
TI  - Randomization and concealment in surgical trials: a comparison between
      orthopaedic and non-orthopaedic randomized trials.

PMID- 15565304
TI  - Perforated right colonic diverticulitis complicating pregnancy at 37 weeks'
      gestation.

PMID- 15565305
TI  - The SIS extracellular matrix scaffold-preliminary results of use in congenital
      diaphragmatic hernia (CDH) repair.
AB  - There is no ideal bio-tensile material for tissue replacement in paediatric
      surgical conditions. A variety of materials have been described to replace or
      reinforce tissue deficits in congenital diaphragmatic hernia (CDH). The problems
      with these materials range from extensive surgery to body wall deformity and
      hernia recurrence. The ideal graft would be safe, strong, have the potential to
      grow and not require replacement, not affect chest wall development or produce
      deformity, and have minimal risk of recurrence. Surgisis is a biomaterial
      composed of porcine intestinal submucosa that provides inherent tensile strength
      as a collagen lattice and is ultimately replaced by native collagen tissue. Our
      objective was to prospectively assess the utility of Surgisis as a replacement
      graft in a cohort of 10 children undergoing primary or recurrent CDH repair. The
      graft was well tolerated, and there was no recurrence of herniation. We conclude
      that Surgisis collagen mesh may be a useful alternative for tissue replacement or
      reinforcement in difficult cases of CDH and diaphragmatic agenesis. The
      biological framework of Surgisis may also prove useful in other situations of
      complex tissue loss in children.

PMID- 15565306
TI  - Experience with anorectal malformations in Ile-Ife, Nigeria.
AB  - The study was carried out to determine the characteristics and outcome of
      management of anorectal malformations (ARM) in Nigerian children at the Obafemi
      Awolowo University Teaching Hospitals Complex (OAUTHC) in Ile-Ife, Nigeria,
      between January 1986 and December 2002. Eighty-six children with ARM were
      studied, 48 males and 38 females. Only 12 (13.9%) presented to the hospital
      within 24 h of birth. Twenty-four (27.9%) patients had one or more associated
      congenital anomalies, with oesophageal atresia with tracheo-oesophageal fistula
      being the most common associated malformation. A low variety was identified in 26
      (30.2%) cases, while 60 (69.8%) had intermediate or high lesions. Twenty-two
      patients with the low type of anomaly were offered primary anoplasty in the
      neonatal period, whereas 59 patients with intermediate or high malformations were
      offered a preliminary colostomy. A definitive pull-through procedure was
      ultimately performed in 27 of these 59 cases. Twenty-six patients (30.2%) died.
      Infection and severe associated malformations were responsible for most (65%) of
      the deaths. Early results of definitive surgery among survivors were generally
      good after a mean follow-up period of 13 months. Late presentation, inadequate
      facilities for neonatal intensive care, and paucity of specialist supportive
      personnel appear to have negatively influenced the outcome of treatment in our
      environment. Increasing awareness and availability of medical facilities and
      specialists are needed.

PMID- 15565307
TI  - Freshwater to seawater acclimation of juvenile bull sharks (Carcharhinus leucas):
      plasma osmolytes and Na+/K+-ATPase activity in gill, rectal gland, kidney and
      intestine.
AB  - This study examined the osmoregulatory status of the euryhaline elasmobranch
      Carcharhinus leucas acclimated to freshwater (FW) and seawater (SW). Juvenile C.
      leucas captured in FW (3 mOsm l(-1) kg(-1)) were acclimated to SW (980-1,000 mOsm
      l(-1) kg(-1)) over 16 days. A FW group was maintained in captivity over a similar
      time period. In FW, bull sharks were hyper-osmotic regulators, having a plasma
      osmolarity of 595 mOsm l(-1) kg(-1). In SW, bull sharks had significantly higher
      plasma osmolarities (940 mOsm l(-1) kg(-1)) than FW-acclimated animals and were
      slightly hypo-osmotic to the environment. Plasma Na(+), Cl(-), K(+), Mg(2+),
      Ca(2+), urea and trimethylamine oxide (TMAO) concentrations were all
      significantly higher in bull sharks acclimated to SW, with urea and TMAO showing
      the greatest increase. Gill, rectal gland, kidney and intestinal tissue were
      taken from animals acclimated to FW and SW and analysed for maximal Na(+)/K(+)
      ATPase activity. Na(+)/K(+)-ATPase activity in the gills and intestine was less
      than 1 mmol Pi mg(-1) protein h(-1) and there was no difference in activity
      between FW- and SW-acclimated animals. In contrast Na(+)/K(+)-ATPase activity in
      the rectal gland and kidney were significantly higher than gill and intestine and
      showed significant differences between the FW- and SW-acclimated groups. In FW
      and SW, rectal gland Na(+)/K(+)-ATPase activity was 5.6+/-0.8 and 9.2+/-0.6 mmol
      Pi mg(-1) protein h(-1), respectively. Na(+)/K(+)-ATPase activity in the kidney
      of FW and SW acclimated animals was 8.4+/-1.1 and 3.3+/-1.1 Pi mg(-1) protein h(
      1), respectively. Thus juvenile bull sharks have the osmoregulatory plasticity to
      acclimate to SW; their preference for the upper reaches of rivers where salinity
      is low is therefore likely to be for predator avoidance and/or increased food
      abundance rather than because of a physiological constraint.

PMID- 15565308
TI  - Dynamic digestive responses to increased energy demands in the leaf-eared mouse
      (Phyllotis darwini).
AB  - A major area of interest in comparative physiology has been to understand how
      animals cope with changing environmental demands in time and space. The digestive
      system has been identified as one of the more sensitive systems to changes in
      environmental conditions. However, most research on this topic has evaluated
      these effects during peak energetic demands, which do not allow for evaluation of
      the dynamics of the digestive response along a more natural continuous gradient
      of environmental conditions. We examined phenotypic flexibility in digestive
      responses of the leaf-eared mouse Phyllotis darwini to increments in total energy
      demands (via sequential exposure to 26, 12 and 0 degrees C). Additionally, we
      evaluated the effect of a moderate energy demand (12 degrees C) over three
      different time periods (7, 17 and 27 days) on digestive traits. Moderate
      increases in energy demand were associated with changes in the distribution of
      digesta in the gut, whereas higher increases in energy demand involved increases
      in the tissue mass of digestive organs. Time-course analysis showed that at 12
      degrees C practically all digestive variables reached stable values within 7
      days, which is in agreement with empirical data and theoretical deductions from
      cellular turnover rates. We conclude that although the input of energy and
      nutrients into the digestive tract is typically periodic, many aspects of
      digestive physiology are likely to be flexible in response to environmental
      variability over both short-term (daily) and long-term (seasonal) time scales.

PMID- 15565309
TI  - Does food shortage delay development of homeothermy in European shag nestlings
      (Phalacrocorax aristotelis)?
AB  - Nestlings seem to face a trade-off between reducing the basal level of energy
      metabolism, as an energy-saving response, and maintaining thermogenic capacity
      during temporal food shortage. In the present study we examined developmental
      responses to short-term diet restriction of 12-16 day old nestling European shags
      kept under laboratory conditions and tested whether temporal food shortage delay
      the development of homeothermy. During food shortage the European shag nestlings
      substantially reduced basal level of energy metabolism, resulting in significant
      energy savings. The reduction in basal level of energy metabolism corresponded
      with a reduction in peak metabolic rate. At the same time, the low peak metabolic
      rate of diet-restricted nestlings was offset by a lower mass-specific minimal
      thermal conductance, and an increased mass-specific absolute scope. Consequently,
      the insulation and the portion of peak metabolic rate available for regulatory
      thermogenesis seemed to develop normally, as expected from age, during the period
      of food shortage. Further, the degree of homeothermy, measured as the index of
      homeothermy, was not significantly lower in diet-restricted nestlings compared to
      controls at the same age. We conclude that temporal food shortage did not
      significantly delay the development of homeothermy in the European shag nestlings
      despite substantial reductions in basal level of energy metabolism and peak
      metabolic rate.

PMID- 15565310
TI  - 65Zn2+ transport by lobster hepato-pancreatic baso-lateral membrane vesicles.
AB  - The lobster (Homarus americanus) hepato-pancreatic epithelial baso-lateral cell
      membrane possesses three transport proteins that transfer calcium between the
      cytoplasm and hemolymph: an ATP-dependent calcium ATPase, a sodium-calcium
      exchanger, and a verapamil-sensitive cation channel. We used standard
      centrifugation methods to prepare purified hepato-pancreatic baso-lateral
      membrane vesicles and a rapid filtration procedure to investigate whether
      (65)Zn(2+) transfer across this epithelial cell border occurs by any of these
      previously described transporters for calcium. Baso-lateral membrane vesicles
      were osmotically reactive and exhibited a time course of uptake that was linear
      for 10-15 s and approached equilibrium by 120 s. In the absence of sodium,
      (65)Zn(2+) influx was a hyperbolic function of external zinc concentration and
      followed the Michaelis-Menten equation for carrier transport. This carrier
      transport was stimulated by the addition of 150 microM ATP (increase in K(m) and
      J(max)) and inhibited by the simultaneous presence of 150 micromol l(-1) ATP+250
      micromol l(-1) vanadate (decrease in both K(m) and J(max)). In the absence of
      ATP, (65)Zn(2+) influx was a sigmoidal function of preloaded vesicular sodium
      concentration (0, 5, 10, 20, 30, 45, and 75 mmol l(-1)) and exhibited a Hill
      Coefficient of 4.03+/-1.14, consistent with the exchange of 3 Na(+)/1Zn(2+).
      Using Dixon analysis, calcium was shown to be a competitive inhibitor of baso
      lateral membrane vesicle (65)Zn(2+) influx by both the ATP-dependent (K(i)=205
      nmol l(-1) Ca(2+)) and sodium-dependent (K(i)=2.47 micromol l(-1) Ca(2+))
      transport processes. These results suggest that zinc transport across the lobster
      hepato-pancreatic baso-lateral membrane largely occurred by the ATP-dependent
      calcium ATPase and sodium-calcium exchanger carrier proteins.

PMID- 15565311
TI  - MR relaxometry and 1H MR spectroscopy for the determination of iron and
      metabolite concentrations in PKAN patients.
AB  - The influence of iron deposits on T2 values and the content of metabolites in the
      brain of three patients with DNA proved pantothenate kinase-associated
      neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome) was studied. An
      eye-of-the-tiger sign, a typical MR finding for PKAN, was observed in two
      patients with the same mutation. A hypointensive lesion in a whole globus
      pallidus was observed in the third patient with the additional mutation. T2
      values in the globus pallidus of the patients were about 40% shorter than in
      controls (71/48 ms in controls vs. patients), which corresponds to the increase
      of Fe concentration based on the ferritin basis from 17 mg for controls to 48 mg
      (100 g wet brain weight) in PKAN patients. 1H MR spectroscopy (MRS) has mainly
      been used to describe neuronal damage represented by decreased NAA (6.4 mmol vs.
      9 mmol) and Cr/PCr (7.0 mmol vs. 9.8 mmol) concentrations in the basal ganglia
      region of the patient group to controls; MRS is much more case-sensitive and
      describes individual development of the disease as demonstrated in the difference
      between the spectra of typical PKAN patients (1, 2), and the patient (3) with
      atypical PKAN development. Any significant changes of metabolite concentration
      with the exception glutamine, glutamate and GABA were found in the white matter.

PMID- 15565312
TI  - Transdiaphragmatic peritoneal hernia complicating peritoneal dialysis:
      demonstration with spiral computed tomography peritoneography and peritoneal
      scintigraphy.
AB  - The authors describe a rare case of peritoneal transdiaphragmatic hernia
      discovered immediately after a car accident in a young male patient on peritoneal
      dialysis. The potential role of CT peritoneography and peritoneal scintigraphy to
      demonstrate and understand thoracic complications of ambulatory peritoneal
      dialysis is discussed.

PMID- 15565313
TI  - Lung MRI at 3.0 T: a comparison of helical CT and high-field MRI in the detection
      of diffuse lung disease.
AB  - The purpose of this study was to evaluate the feasibility of high-field magnetic
      resonance imaging (MRI) of the lung using a T2-weighted fast-spin echo (TSE)
      sequence. Comparison was made with helical computed tomography CT findings in
      patients with diffuse pulmonary diseases. Prospective segment-wise analysis of
      high-field MR imaging findings in 15 patients with diffuse pulmonary diseases was
      made using helical CT and HRCT as the standard of reference. The MR studies were
      performed on a 3.0-T whole body system (Intera 3T, Philips Medical Systems) using
      a T2w TSE sequence with respiratory and cardiac gating (TE 80 ms TR 1,500-2,500
      ms; turbo factor 17; 22 slices with 7/2-mm slice thickness and gap; 256x192
      matrix). MR artifacts were graded on a three-point scale (low, moderate, high).
      Lung MR studies were prospectively analyzed segment-by-segment and diagnosed as
      healthy or pathological; results were compared with helical CT findings. In all
      15 patients, MR imaging of the lung was successful. All 15 MR studies were
      compromised by artifacts; however, the severity of these artifacts was classified
      as low or moderate in 8/15, respectively, 7/15 cases. A total of 143/285 lung
      segments showed diffuse lung disease in helical CT. With MRI, 133 of these 143
      segments (93%) were judged to be diseased. The ten segments that received false
      negative MR diagnoses displayed non-acute pulmonary lesions with inherently low
      proton density (scars, granulomas). MRI at 3.0 T can detect diffuse pulmonary
      disease with a high sensitivity. Based on this experience, further pulmonary
      studies with high-field systems appear justified and promising.

PMID- 15565314
TI  - Multidetector CT enteroclysis: comparison of the reading performance for axial
      and coronal views.
AB  - The purpose of this study was to compare the diagnostic performance of axial and
      coronal views in multidetector CT enteroclysis (MDCTE). We retrospectively
      evaluated 48 patients with pathological correlation investigated by MDCTE for
      small bowel disorders. After nasojejunal administration of 2 l of 5%
      methylcellulose axial arterial and venous acquisition of MDCTE was followed by
      coronal reconstructions using equal slice thicknesses of 2.5 mm with 2 mm
      increments. Spatial resolution of both planes was evaluated by phantom. Three
      radiologists independently read axial and coronal images concerning 12
      pathological features. The interobserver agreement and time of reading was
      calculated. Sensitivity and specificity resulted from comparison with
      histopathology (n=39) or follow-up (n=9). Phantom study revealed higher spatial
      resolution for axial than coronal views, whatever reconstruction interval was
      used. However, spatial frequency always remained high. Most pathological signs,
      such as bowel wall thickening (BWT), bowel wall enhancement (BWE) and
      intraperitoneal fluid (IPF), showed better interobserver agreement on axial than
      coronal views (BWT: 0.61 vs. 0.44; BWE: 0.56 vs. 0.5; IPF:0.53 vs. 0.43). The
      Wilcoxon signed-rank test revealed significantly higher sensitivity for axial
      than coronal views (P=0.0453); the time of reading was significantly shorter for
      the latter (P=0.0146). The diagnostic value of axial slices is superior to
      coronal reconstructions despite the reduced data volume and display of the
      physiological course of bowel loops on the coronal plane.

PMID- 15565315
TI  - Assessment of right ventricular function by 16-detector-row CT: comparison with
      magnetic resonance imaging.
AB  - The purpose of this study was to determine right ventricular (RV) function from
      16-detector-row CT by using two different software tools in comparison with MRI.
      Nineteen patients underwent cardiac CT. (1) With semiautomated contour detection
      software end-diastolic and end-systolic RV volumes were determined from short
      axis CT reformations (MPR) created at every 10% of the RR-interval. (2) End
      systolic and end-diastolic axial images were transformed to 3D to determine the
      volumes by using a threshold-supported reconstruction algorithm. Steady-state
      free-precession cine-MRI of the heart was done in short-axis orientation. RV
      function could not be analyzed in one patient because of sternal wire artifacts
      in MRI. Mean end-diastolic (155.4+/-54.6 ml) and end-systolic (79.1+/-37.0 ml) RV
      volumes determined with MPR correlated well with MRI [151.9+/-53.7 ml (r=0.98)
      and 75.0+/-36.0 ml (r=0.96), respectively (P<0.001)]. RV stroke volume (76.2+/
      20.2 ml for MPR-CT, 76.9+/-20.7 ml for MRI, r=0.93) showed a good correlation and
      RV ejection fraction (50.8+/-8.4% for MPR-CT, 51.9+/-7.4% for MRI, r=0.74) only a
      moderate one. Threshold supported 3D reconstructions revealed insufficient
      correlations with MRI (r=0.31-0.59). MPR-based semiautomated analysis of cardiac
      16 detector-row CT allows for RV functional analysis. The results correlate well
      with MRI findings. Threshold value-supported 3D reconstructions did not show
      satisfying results because of inhomogeneities of RV contrast enhancement.

PMID- 15565316
TI  - MDCT of the proximal anastomoses created by nitinol implants in coronary artery
      bypass grafting: a retrospective two-observer evaluation.
AB  - The purpose of this study was to investigate the proximal anastomosis of CABG
      grafts created by a nitinol aortic connector. After receiving CABG, 33 patients
      underwent CT examination of the heart. On the same patients, CT was performed on
      postoperative day 5 (4-row CT, group A) and again 1 year thereafter (16-row CT,
      group B). Twenty-three ACVB to RCX and 27 ACVB to RCA grafts were included. Every
      anastomosis was reviewed under different reformations (MIP, MPR and VRT).
      Interobserver correlation was determined. Five days postoperatively, 48/50
      anastomoses were classified as patent. One year postoperatively, 42/50
      anastomoses were classified as patent. In both groups, the aortic connector could
      be visualized with good quality: 1.82+/-1.10 (group A) and 1.93+/-1.22 (group B)
      for ACVB to RCA, similar results for ACVB to RCX grafts (MPR). Image quality at
      the aortic connector site did not display a significant difference for any
      reformation between groups (P>0.05). Within groups, MPR displayed better
      visualization than MIP and VRT (P<0.05). In the presence of metal implants, CT
      provides reliable data in evaluation of the proximal anastomosis. Sixteen-row CT
      does not bring a significant benefit to image quality. MPR displayed the best
      visualization within both groups.

PMID- 15565317
TI  - Coronary arteries: assessment of image quality and optimal reconstruction window
      in retrospective ECG-gated multislice CT at 375-ms gantry rotation time.
AB  - Our objective was to evaluate the image quality of a 16-slice CT system with a
      rotation time of 375 ms in the assessment of coronary arteries. One hundred
      patients underwent iodine-enhanced CT coronary angiography within a single breath
      hold. Images were reconstructed in diastole, 300, 350, 400, 450, 500 and 550 ms
      prior to the onset of the next R-wave using absolute reverse retrospective ECG
      gating. The 15 coronary segments of the AHA classification were consensually
      reviewed by two radiologists. On the whole, best quality imaging was obtained
      with reconstruction intervals of -350 ms and -400 ms in high percentages of each
      segment (P<0.0001). Only 6.2% of the arteries with a diameter greater than or
      equal to 1.5 mm were not assessable because of extensive calcifications (3.9%),
      cardiac motion artifacts (1.9%), lack of enhancement (0.2%) and stent artifacts
      (0.3%). In patients with a heart rate above 70 beats per minute, the percentage
      of assessable segments decreased to 88%, while at a lower heart rate it increased
      to 95%. In 61% of the patients, all segments were assessable. In conclusion, this
      generation of CT technique may allow visualization of coronary arteries with a
      low percentage of non-assessable segments.

PMID- 15565318
TI  - Gallbladder wall thickening: MR imaging and pathologic correlation with emphasis
      on layered pattern.
AB  - The aim of this study was to correlate MR findings of gallbladder wall thickening
      with pathologic findings on the basis of the layered pattern and to evaluate the
      diagnostic value of MR imaging in gallbladder disease. We retrospectively
      evaluated the source images of HASTE sequences for MR cholangiography in 144
      patients with gallbladder wall thickening. The layered pattern of thickened wall
      was classified into four patterns. Type 1 shows two layers with a thin
      hypointense inner layer and thick hyperintense outer layer. Type 2 has two layers
      of ill-defined margin. Type 3 shows multiple hyperintense cystic spaces in the
      wall. Type 4 shows diffuse nodular thickening without layering. MR findings of a
      layered pattern of thickened gallbladder were well correlated with
      histopathology. Chronic cholecystitis matched to type 1, acute cholecystitis
      corresponded to type 2, adenomyomatosis showed type 3, and the gallbladder
      carcinomas showed type 4. All four layered patterns were associated with PPV of
      73% or greater, sensitivity of 92% or greater and specificity of 95% or greater.
      Our results indicate that MR findings of gallbladder wall thickening are
      characteristic in each entity and correlate well with pathologic findings. The
      classification of the layered pattern may be valuable for interpreting thickened
      gallbladder wall.

PMID- 15565319
TI  - Multi-detector row computed tomography of the heart: does a multi-segment
      reconstruction algorithm improve left ventricular volume measurements?
AB  - A multi-segment cardiac image reconstruction algorithm in multi-detector row
      computed tomography (MDCT) was evaluated regarding temporal resolution and
      determination of left ventricular (LV) volumes and global LV function. MDCT and
      cine magnetic resonance (CMR) imaging were performed in 12 patients with known or
      suspected coronary artery disease. Patients gave informed written consent for the
      MDCT and the CMR exam. MDCT data were reconstructed using the standard adaptive
      cardiac volume (ACV) algorithm as well as a multi-segment algorithm utilizing
      data from three, five and seven rotations. LV end-diastolic (LV-EDV) and end
      systolic volumes and ejection fraction (LV-EF) were determined from short-axis
      image reformations and compared to CMR data. Mean temporal resolution achieved
      was 192+/-24 ms using the ACV algorithm and improved significantly utilizing the
      three, five and seven data segments to 139+/-12, 113+/-13 and 96+/-11 ms (P<0.001
      for each). Mean LV-EDV was without significant differences using the ACV
      algorithm, the multi-segment approach and CMR imaging. Despite improved temporal
      resolution with multi-segment image reconstruction, end-systolic volumes were
      less accurately measured (mean differences 3.9+/-11.8 ml to 8.1+/-13.9 ml),
      resulting in a consistent underestimation of LV-EF by 2.3-5.4% in comparison to
      CMR imaging (Bland-Altman analysis). Multi-segment image reconstruction improves
      temporal resolution compared to the standard ACV algorithm, but this does not
      result in a benefit for determination of LV volume and function.

PMID- 15565320
TI  - Hyperintense globus pallidus on T1-weighted MR imaging in acute kernicterus: is
      it common or rare?
AB  - Globus pallidus involvement is a well-known magnetic resonance (MR) imaging
      finding of acute kernicterus. However, it is not clear how early the involvement
      of globus pallidus occurs and whether or not it is seen in every case. Therefore,
      we aimed to investigate the globus pallidus involvement in 13 neonates with acute
      kernicterus by MR imaging. Thirteen neonates who were admitted with jaundice,
      encephalopathy and indirect hyperbilirubinemia (mean, 37.0 mg/dl) were
      prospectively evaluated with cranial MR imaging. Pathological signal changes were
      noted concerning the globus pallidus. Eight of the 13 patients demonstrated
      bilateral, symmetric increased signal intensity in the globus pallidus on T1
      weighted MR imaging. These lesions were not apparent on T2-weighted images.
      Multiple parenchymal punctuate T1 hyperintense lesions were detected in one
      patient without globus pallidus involvement. This appearance was consistent with
      hemorrhage. The MR imaging findings of the other four patients showed no evidence
      of abnormality. The symmetric involvement of globus pallidus seen as hyperintense
      on T1-weighted MR imaging is a common and characteristic finding of acute
      kernicterus.

PMID- 15565321
TI  - Cryopreservation of immature seeds of Bletilla striata by vitrification.
AB  - An efficient protocol was established for the cryopreservation of immature seeds
      of a terrestrial orchid, Bletilla striata. Immature seeds collected 2-4 months
      after pollination (MAP) were treated using three different cryogenic procedures:
      (1) direct plunging into liquid nitrogen, (2) vitrification, and (3)
      vitrification with preculture. When immature seeds collected 3 MAP and 4 MAP were
      precultured for 3 days on New Dogashima medium supplemented with 0.3 M sucrose
      and cryopreserved by vitrification, the survival rate after preservation, as
      assessed by staining with 2,3,5-triphenyltetrazolium chloride, was 92% and 81%,
      respectively. Immature seeds thus treated showed no decrease in germination rate
      relative to untreated immature seeds, and they developed into normal plantlets in
      vitro.

PMID- 15565323
TI  - [Clinical pathology in the Hanseatic City of Lubeck from the planning of an
      institute to the formation of the "Medizinische Hochschule"].
AB  - The formation of an university institute of pathology at the Hanseatic city of
      Lubeck preceded a long, changeful planning, accompanied by a chain of historical
      events. In the 19th century, Lubeck owned seven different places for clinical or
      forensic autopsies. Thus, in the first years of the 20th century it was generally
      called for the formation of a "Central Institute of Pathology" that was completed
      after all in the year 1927. Two years later, Eberhard von Praun became head of
      the institute and was immediately confronted with the "Lubeck-disaster". He was
      followed 1935 by Ernst Jeckeln, who identified the "Enteritis necroticans" which
      appeared in North Germany in the first years after the "Second World War". He
      called the disease "Darmbrand", a term that is since then internationally used.
      Jeckeln became the first "Ordinarius for Pathology" at the "Medical Academy
      Lubeck", which was associated to the "University of Kiel". His long-time
      colleague was Alfred Wegener, who identified the "Wegener's granulomatosis". In
      the year 1972 Alfred Gropp became head of the institute, an all-round scientist
      and pathologist, e.g. well-known in the field of developmental pathology. During
      his term, the "Medical Academy" got the university status and was named
      "Medizinische Hochschule Lubeck".

PMID- 15565322
TI  - Sin3: a flexible regulator of global gene expression and genome stability.
AB  - SIN3 was first identified genetically as a global regulator of transcription.
      Sin3 is a large protein composed mainly of protein-interaction domains, whose
      function is to provide structural support for a heterogeneous Sin3/histone
      deacetylase (HDAC) complex. The core Sin3/HDAC complex is conserved from yeast to
      man and consists of eight proteins. In addition to HDACs, Sin3 can sequester
      other enzymatic functions, including nucleosome remodeling, DNA methylation, N
      acetylglucoseamine transferase activity, and histone methylation. Since the
      Sin3/HDAC complex lacks any DNA-binding activity, it must be targeted to gene
      promoters by interacting with DNA-binding proteins. Although most research on
      Sin3 has focused on its role as a corepressor, mounting evidence suggests that
      Sin3 can also positively regulate transcription. Furthermore, Sin3 is key to the
      propagation of epigenetically silenced domains and is required for centromere
      function. Thus, Sin3 provides a platform to deliver multiple combinations
      modifications to the chromatin, using both sequence-specific and sequence
      independent mechanisms.

PMID- 15565324
TI  - Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2.
AB  - PURPOSE: The aim of this study was to investigate the transport mechanisms of
      transporters that contribute to the intestinal uptake of 7-ethyl-10
      hydroxycamptothecin (SN-38). METHODS: Human intestinal epithelial Caco-2 cells
      were used to investigate the mechanistic basis of transepithelial uptake of SN
      38. We investigated the characteristics of SN-38 uptake into Caco-2 cells. The
      effects of baicalin and sulfobromophthalein (BSP) on the uptake of SN-38 by Caco
      2 cells were examined. RESULTS: Uptake of SN-38 was significantly reduced at 4
      degrees C. Baicalin inhibited the uptake of SN-38 in a concentration-dependent
      manner. BSP significantly reduced the uptake of SN-38. However, probenecid,
      pravastatin and grepafloxacin did not affect the uptake of SN-38. CONCLUSIONS:
      The results suggest that a specific transport system mediates the uptake of SN-38
      across the apical membrane in Caco-2 cells.

PMID- 15565325
TI  - Antitumor activity of albendazole against the human colorectal cancer cell line
      HT-29: in vitro and in a xenograft model of peritoneal carcinomatosis.
AB  - The peritoneal surface remains an important failure site for patients with
      colorectal cancer. We have recently shown that albendazole (ABZ), a safe and
      effective anthelmintic drug, has profound antitumor activity in hepatocellular
      cancer. Furthermore, albendazole also possesses unique physiochemical and
      pharmacokinetic properties probably making it a potential drug for use in the
      regional treatment of peritoneal carcinomatosis (PC). The current study was
      therefore designed to investigate this concept under both in vitro and in vivo
      conditions using human colorectal cancer cells HT-29. In cell culture, studies
      were conducted to investigate the effect of ABZ and its major metabolites,
      albendazole sulfoxide (ABZ-SO) and albendazole sulfone (ABZ-SO2) on the growth of
      human colorectal cell line HT-29. We also investigated the effects of ABZ on the
      cell cycle and the possible induction of apoptosis in these cells. Male nude mice
      inoculated intraperitoneally (i.p.) with HT-29 cells were treated with various
      schedules of ABZ given i.p. or orally for 6 weeks. Response was evaluated as the
      number of peritoneal tumor nodules present in animals at the end of the treatment
      period. In vitro, ABZ treatment of cells for 5 days led to profound inhibition of
      growth. (3)H-Thymidine assay and trypan blue viable cell counts confirmed the
      dose- and time-dependency of the ABZ effect, while recovery experiments revealed
      the reversible nature of this inhibition. ABZ-SO and ABZ-SO2 were also evaluated
      in cell culture studies and compared with the parent drug. In HT-29 cells, the
      IC(50) values were calculated to be 0.12 microM for ABZ and 2.35 microM for ABZ
      SO. The other metabolite, ABZ-SO2, was completely inactive. Studies on the
      mechanism of ABZ action, revealed arrest of HT-29 cells at the G(2)/M phase of
      the cell cycle, while TUNEL, DNA laddering and caspase-3 activity all confirmed
      ABZ induced apoptosis. In nude mice with peritoneal HT-29 xenografts, ABZ
      profoundly inhibited peritoneal tumor growth. While alternate i.p. dosing (ABZ,
      150 mg/kg) led to the highest degree of tumor growth suppression (P<0.001),
      schedules such as once-weekly dosing and even a single dose for the entire course
      of treatment (6 weeks) were also effective in reducing peritoneal tumor growth.
      However, no such activity was observed when ABZ was administered orally. This
      study shows for the first time the potent effect of regionally administered ABZ
      in suppressing the growth of peritoneal tumors of human colorectal origin. The
      effect is thought to be brought about by arresting tumor cells at the G(2)/M
      phase of the cycle and apoptosis. These findings provide evidence for potential
      value of ABZ in the treatment of regional PC arising from colorectal cell lines.

PMID- 15565326
TI  - Description of paclitaxel resistance-associated genes in ovarian and breast
      cancer cell lines.
AB  - PURPOSE: To identify genes involved in the paclitaxel resistance phenotype.
      METHODS: High-density Affymetrix HG-U95Av2 microarrays were used to quantify gene
      expression in the resulting cell lines, SKOV-3TR, OVCAR8TR and MCF-7TR, and their
      drug-sensitive parental lines, SKOV-3, OVCAR8 and MCF-7. RESULTS: Three
      paclitaxel-resistant human ovarian and breast cancer cell lines were established.
      We identified 790 (SKOV-3TR), 689 (OVCAR8TR) and 964 (MCF-7TR) transcripts that
      were more than twofold overexpressed relative to their expression in the
      corresponding parental cell line. A comparison of these transcripts identified
      eight genes that were significantly overexpressed in all three drug-resistant
      daughter cell lines. These genes included MDR1, a gene often implicated in both
      in vitro and in vivo resistance to multiple chemotherapeutics, including
      paclitaxel. The remaining seven genes have not been previously associated with
      resistance to paclitaxel in human cancer. Furthermore, we identified 815 (SKOV
      3TR), 430 (OVCAR8TR) and 332 (MCF-7TR) transcripts that were more than twofold
      decreased relative to their expression in the corresponding parental cell line.
      Comparison of these transcripts identified three genes that were significantly
      underexpressed in all three drug-resistant cell lines, none of which have been
      previously associated with paclitaxel resistance. CONCLUSIONS: Our results
      confirm that the paclitaxel resistance phenotype is associated with a large
      number of transcriptional changes. In addition, acquired paclitaxel resistance
      was associated with distinct transcriptional changes in each of the cell lines
      studied, suggesting that paclitaxel resistance is a complex phenotype that can
      arise through multiple mechanisms.

PMID- 15565327
TI  - Correction of iron-deficient erythropoiesis in the treatment of anemia of chronic
      disease with recombinant human erythropoietin.
AB  - Anemia of chronic disease (ACD) is a frequent complication of chronic
      inflammation in rheumatoid arthritis (RA). Recombinant human erythropoietin
      (rHuEpo) has been shown to be effective in correcting ACD, although with a
      variable rate of nonresponders. The first aim of this trial was to improve the
      response to rHuEpo by parenteral iron supplementation in cases of iron-deficient
      erythropoiesis (IDE). An additional goal was the evaluation of the zinc
      protoporphyrin content of erythrocytes (ZnPP), the soluble transferrin receptor
      (sTrfR) serum concentration, and the hemoglobin (Hb) content of reticulocytes
      (CHr) in stimulated erythropoiesis as diagnostic and prognostic parameters.
      Thirty RA patients with ACD were treated with subcutaneous 150 IU rHuEpo/kg body
      weight twice weekly. Intravenous iron supplementation (200 mg iron sucrose once
      weekly) was added in cases of IDE (n=23), which was defined by the presence of
      two of three criteria: saturation of transferrin (TrfS) < or =15%, hypochromic
      erythrocytes (HypoE) > or =10%, and a serum ferritin (Fn) concentration < or =50
      microg/l. All 28 completers met the treatment goal, with an increase of the
      median Hb concentration from 10.3 g/dl to 13.3 g/dl. Epo treatment and iron
      supplementation was safe and well tolerated in all patients. Monitoring of Fn,
      TrfS, and HypoE every other week allowed a successful correction of anemia.
      Retrospective analysis of the evaluable parameters (CHr, sTrfR, and ZnPP)
      revealed no additional benefit for predicting or monitoring IDE in this setting,
      although the one or other may be advantageous in other therapeutic situations.

PMID- 15565328
TI  - Anatomical modifications of the temporomandibular joint during ageing.
AB  - It is essential to know the normal and pathological changes of ageing in the
      temporomandibular joint (TMJ) because of the frequency of pathology in this joint
      and the increased duration of life in current populations. A study was done on 70
      TMJs harvested from 35 subjects older than 75 years. These joints were studied
      macroscopically, radiologically and histologically. Degenerative pathology of the
      TMJ affected more than 50% of the subjects studied and the disc was perforated in
      7%. Ageing of the TMJ without any degenerative pathology is marked by
      radiographic signs which are not specific to the TMJ (cortical thinning,
      demineralisation). Histologically, amyloid degeneration was present in nearly 50%
      of TMJs studied.

PMID- 15565329
TI  - High-molecular-weight melanoma-associated antigen mimotope immunizations induce
      antibodies recognizing melanoma cells.
AB  - Size and posttranslational modifications are obstacles in the recombinant
      expression of high-molecular-weight melanoma-associated antigen (HMW-MAA).
      Creating a tumor antigen mimic via the phage display technology may be a means to
      overcome this problem for vaccine design. In this study, we aimed to generate an
      immunogenic epitope mimic of HMW-MAA. Therefore we screened a linear 9mer phage
      display peptide library, using the anti-HMW-MAA monoclonal antibody (mAb)
      225.28S. This antibody mediates antibody-dependent cellular cytotoxicity (ADCC)
      and has already been used for anti-idiotype therapy trials. Fifteen peptides were
      selected by mAb 225.28S in the biopanning procedure. They share a consensus
      sequence, but show only partial homology to the amino acid sequence of the HMW
      MAA core protein, indicating mimicry with a conformational epitope. One mimotope
      was chosen to be fused to albumin binding protein (ABP) as an immunogenic
      carrier. Immunoassays with 225.28S indicated that the mimotope fusion protein was
      folded correctly. Subsequently, the fusion protein was tested for immunogenicity
      in BALB/c mice. The induced anti-mimotope antibodies recognized HMW-MAA of 518A2
      human melanoma cells, whereas sera of mice immunized with the carrier ABP alone
      showed no reactivity. These anti-mimotope antibodies were capable of inducing
      specific lysis of 518A2 melanoma cells in ADCC assays with murine effector cells.
      In conclusion, the presented data indicate that mimotopes fused to an immunogenic
      carrier are suitable tools to elicit epitope-specific anti-melanoma immune
      responses.

PMID- 15565330
TI  - Immunotherapy for superficial bladder cancer.
AB  - The treatment of superficial bladder cancer requires adjuvant therapies besides
      transurethral resection because of a high recurrence rate after this standard
      treatment alone. Current adjuvant therapies involve intravesical chemotherapy for
      patients at low and intermediate risk for recurrence and progression, and
      intravesical bacillus Calmette-Guerin for patients at intermediate and high risk.
      However, these adjuvant therapies fail in a significant number of patients,
      dictating the need for new and improved adjuvant treatment modalities for
      superficial bladder cancer. Immunotherapy aiming at the modulation of the immune
      system of the patient is a promising alternative adjuvant. This review discusses
      the current status of the clinical development of various immunotherapy
      approaches for superficial bladder cancer, including passive immunotherapy,
      immune stimulants, immunogene therapy and cancer vaccination.

PMID- 15565331
TI  - [18F]FLT-PET in oncology: current status and opportunities.
AB  - In recent years, [18F]-fluoro-3'-deoxy-3'-L: -fluorothymidine ([18F]FLT) has been
      developed as a proliferation tracer. Imaging and measurement of proliferation
      with PET could provide us with a non-invasive staging tool and a tool to monitor
      the response to anticancer treatment. In this review, the basis of [18F]FLT as a
      proliferation tracer is discussed. Furthermore, an overview of the current status
      of [18F]FLT-PET research is given. The results of this research show that
      although [18F]FLT is a tracer that visualises cellular proliferation, it also has
      certain limitations. In comparison with the most widely used PET tracer,
      [18F]FDG, [18F]FLT uptake is lower in most cases. Furthermore, [18F]FLT uptake
      does not always reflect the tumour cell proliferation rate, for example during or
      shortly after certain chemotherapy regimens. The opportunities provided by, and
      the limitations of, [18F]FLT as a proliferation tracer are addressed in this
      review, and directions are given for further research, taking into account the
      strong and weak points of the new tracer.

PMID- 15565332
TI  - Intravenous pyogenic granuloma or intravenous lobular capillary hemangioma.
AB  - Lobular capillary hemangioma is a vascular neoplasm that commonly occurs as a
      cutaneous tumor. When it involves the skin and mucosal surfaces, ulceration and
      suppuration may occur, hence the classic term of pyogenic granuloma. Intravenous
      pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that
      usually occurs in the veins of the neck and upper extremities. We report the
      ultrasonographic and magnetic resonance imaging findings of a pyogenic
      intravenous granuloma localized in the right cephalic vein. The imaging and
      pathological findings and the differential diagnoses are discussed.

PMID- 15565333
TI  - Effect of Sorghum vulgare phosphoenolpyruvate carboxylase and Lactococcus lactis
      pyruvate carboxylase coexpression on succinate production in mutant strains of
      Escherichia coli.
AB  - Sorghum vulgare phosphoenolpyruvate carboxylase (PEPC) and Lactococcus lactis
      pyruvate carboxylase (PYC) were overexpressed in Escherichia coli concurrently to
      improve the production of succinate, a valuable industrial specialty chemical.
      This coexpression system was also applied to E. coli mutant strains strategically
      designed by inactivating the competing pathways of succinate formation. The
      highest level of succinate production was observed in E. coli strains
      coexpressing both PEPC and PYC when compared with E. coli strains individually
      overexpressing either PEPC or PYC. Lactate production was also significantly
      reduced with PEPC and PYC coexpression. Lactate and acetate pathways were
      inactivated to eliminate the competing pathways of succinate formation. Results
      showed that inactivation of both the lactate and acetate pathways with the
      coexpression of PEPC and PYC was most effective in improving succinate
      production. Inactivating the lactate or acetate pathway alone only caused a
      majority of the carbon flux to shift to other metabolites rather than succinate.
      Coexpression of PEPC and PYC was also applied to an E. coli mutant strain
      deficient in lactate dehydrogenase and pyruvate:formate lyase that accumulated a
      substantial amount of the intermediate metabolite pyruvate during growth. Results
      showed that PEPC and PYC coexpression was effective in depleting pyruvate
      accumulation and increasing the production of metabolites.

PMID- 15565334
TI  - Characterisation of a secondary alcohol dehydrogenase from Xanthomonas campestris
      DSM 3586.
AB  - The chromosomal locus NP_636946 of Xanthomonas campestris DSM 3586 (ATCC 33913)
      which was earlier presumed to encode a quinoprotein glucose dehydrogenase has
      been cloned, expressed in Escherichia coli and the recombinant enzyme has been
      characterised. It was found to have no glucose dehydrogenase activity but to be
      active on many different polyols and diols, aliphatic alcohols, certain aldonic
      acids and amino-sugars. The product of D: -gluconic acid oxidation was 5-keto-D: 
      gluconic acid. The enzyme differs from polyol/gluconate dehydrogenases found in
      Gluconobacter by its single-chain architecture, different substrate specificity
      and much higher (20- to 30-fold) expression level in E.coli.

PMID- 15565335
TI  - Mycotoxins as harmful indoor air contaminants.
AB  - Fungal metabolites (mycotoxins) that pose a health hazard to humans and animals
      have long been known to be associated with mold-contaminated food and feed. In
      recent times, concerns have been raised about exposures to mycotoxin-producing
      fungi in indoor environments, e.g., damp homes and buildings. The principal
      mycotoxins that contaminate food and feed (alfatoxins, fumonisins, ochratoxin A,
      deoxynivalenol, zearalenone) are rarely if ever found in indoor environments, but
      their toxicological properties provide an insight into the difficulties of
      assessing the health effects of related mycotoxins produced by indoor molds.
      Although the Penicillium and Aspergillus genera of fungi are major contaminants
      of both food and feed products and damp buildings, the particular species and
      hence the array of mycotoxins are quite different in these environments. The
      mycotoxins of these indoor species and less common mycotoxins from Stachybotrys
      and Chaetomium fungi are discussed in terms of their health effects and the need
      for relevant biomarkers and long-term chronic exposure studies.

PMID- 15565336
TI  - The polymorphisms of Tim-1 promoter region are associated with rheumatoid
      arthritis in a Korean population.
AB  - It has been determined that the family of T-cell immunoglobulin domain and mucin
      domain (TIM) proteins is expressed on T cells. A member of the TIM family, TIM-1,
      is considered to be a membrane protein associated with the development of Th2
      biased immune responses and selectively expressed on Th2 cells. We previously
      showed that the exon 4 variations of Tim-1 are associated with susceptibility to
      allergic diseases, as well as autoimmune diseases such as rheumatoid arthritis
      (RA). In this study, we assessed the association between genotype and allele
      frequencies of the Tim-1 gene promoter region, in both RA patients and the
      controls without RA, using polymerase chain reaction-restriction fragment length
      polymorphism and single-base extension methods. We further investigated the
      relationships among the genotypes of each polymorphism and C-reactive protein or
      rheumatoid factor levels in RA patients. The genotype and allele frequencies of
      the -1637A>G polymorphism in RA patients are significantly different from those
      in the non-RA controls (P=0.0004 and P=0.001, respectively). Our results strongly
      suggest that polymorphism in the Tim-1 promoter region might be associated with
      susceptibility to RA.

PMID- 15565337
TI  - Characterization of natural peptide ligands from HLA-DP2: new insights into HLA
      DP peptide-binding motifs.
AB  - Although natural peptide ligands of HLA-DR and HLA-DQ molecules have been
      extensively studied, information about peptides naturally bound to HLA-DP is
      limited. Here we describe HLA-DP2 peptide ligands corresponding to 24 different
      source proteins that were identified by peptide pool elution and mass
      spectrometry sequencing from HLA-DP2 molecules expressed on EBV-LCLs. Sequencing
      analysis led to the identification of both promiscuous and allele-specific
      peptides. Moreover, the alignment of the natural ligands for HLA-DP2 described
      here, combined with previous results from our group and others concerning HLA-DP2
      antigen presentation and HLA-DP molecular modelling, provide a better
      understanding of HLA-DP2 peptide-binding motifs.

PMID- 15565339
TI  - Severe calcinosis cutis in an infant.
AB  - We report on an infant with severe asphyxia and persistent pulmonary hypertension
      as a newborn. The baby received prolonged intravenous calcium gluconate therapy
      for hypocalcemia. At 5 weeks of age, multiple firm, indurated areas (armor-like
      lesions) were palpable in the subcutaneous tissues of the trunk, arms, legs, and
      face, particularly in skin folds. Roentgenographic study showed generalized soft
      tissue calcifications throughout the body, extremities, and face. Calcinosis
      cutis occurs through a variety of pathogenetic mechanisms. Case reports on
      calcinosis cutis in infants are uncommon, and the calcifications are mostly
      localized. In our patient, they are generalized.

PMID- 15565340
TI  - Angel-shaped phalanges in brachydactyly C: a case report, and speculation on
      pathogenesis.
AB  - We describe a woman and her daughter affected by brachydactyly type C. The
      unusual feature in the child included the striking 'angel-shaped' appearance of
      the proximal phalanges of the index and middle fingers of one hand, whereas more
      typical triangular epiphyses with elongation of their radial side were present at
      the same location in the opposite hand. It is suggested that this peculiar
      phalangeal configuration occurs as a transitory event in early or mid childhood
      in phalanges that are marked by severe ossification delay, which is most
      prominent at the level of the primary ossification centre.

PMID- 15565341
TI  - Magnetic resonance angiography in children: technique, indications, and imaging
      findings.
AB  - Non-invasive imaging of cardiovascular disease in pediatric subjects has been an
      elusive and much anticipated development for many years. Magnetic resonance
      angiography (MRA) has now been established in many institutions as an important
      diagnostic method for evaluating vascular disease in adults. However, MRA
      techniques have disseminated more slowly in children owing to significant
      technical challenges in the pediatric population, including motion, low signal-to
      noise ratio, and suboptimal temporal or spatial resolution. Recent technical
      developments in MRA have addressed many of these issues, and the MRA acquisition
      methods are far more robust than previously used techniques. The objective of
      this manuscript is to discuss the indications for MR imaging, the techniques
      employed, and the imaging findings expected on MRA of children with vascular
      disease.

PMID- 15565342
TI  - Pediatric thoracic CT angiography.
AB  - One of the principal benefits of contemporary multidetector row computed
      tomography (MDCT) has been the ability to obtain high-quality data sets for
      evaluation of the cardiovascular system. The benefits of the greater number of
      detector rows and submillimeter image thicknesses were quickly recognized and are
      especially advantageous in children. For example, since imaging is performed so
      quickly, issues with motion are minimized. This is a substantial benefit of CTA
      compared with MR imaging, the traditional noninvasive cross sectional modality
      for pediatric cardiovascular imaging. This, together with faster and more
      powerful computers, including improved transfer and storage capabilities, offers
      improved depiction of the heart, great vessels, other vasculature, and adjacent
      intrathoracic structures in a fashion that is well accepted by clinical
      colleagues. In order to be successful, however, one must have an understanding of
      the technology and often unique technical considerations in infants and children.
      With this familiarity, excellent cardiovascular examinations can be performed
      even in the most challenging case.

PMID- 15565343
TI  - Intussusception: still work in progress.

PMID- 15565344
TI  - Colonic neuroendocrine carcinoma in a child.
AB  - A 10-year-old boy with congenital immunodeficiency (X-linked agammaglobulinaemia)
      presented with loss of appetite and weight, right-sided abdominal pain, diarrhoea
      and low-grade fever. Radiological investigations with barium follow-through, CT,
      PET and octreotide scans revealed a primary caecal/ascending proximal colonic
      mass with liver and bony metastases. Urine screen for 5HIAA was positive.
      Percutaneous liver biopsy confirmed the diagnosis of neuroendocrine carcinoma.
      The radiological work-up and the usefulness of various imaging modalities in the
      diagnosis of this rare paediatric tumour are discussed. The PET scan demonstrated
      the primary tumour and the metastatic locations more vividly than the octreotide
      scan, which is currently considered to be the most specific imaging modality for
      neuroendocrine masses.

PMID- 15565345
TI  - MRI of the fetal posterior fossa.
AB  - MRI is a useful tool to complement US for imaging of the fetal posterior fossa
      (PF). In France, the discovery of a PF malformation in the fetus frequently leads
      to termination of pregnancy (80% in a personal series). However, despite improved
      accuracy in the diagnosis of PF abnormalities, prognosis remains uncertain. The
      first objective of this review is to document the normal MRI landmarks of the
      developing fetal PF. Because of their thinness, the visibility of the cerebellar
      fissures is dramatically delayed on MRI compared to macroscopic data. An
      important landmark is identification of the primary fissure of the vermis,
      normally seen at around 25-26 weeks' gestation (WG) on the sagittal slice,
      separating the larger posterior lobe from the anterior lobe (volume ratio around
      2:1). The prepyramidal and secondary fissures are usually only identifiable after
      32 WG and the hemispheric fissures are difficult to see until the end of
      pregnancy. Considering the signal changes, high signal on T2-weighted (T2-W)
      sequences is seen from 25 WG in the posterior part of the brain stem (tegmentum
      and ascending sensory tracts) related to myelination. The low signal intensities
      seen within the cerebellum on T2-W images correspond to high cellularity of grey
      matter (deep nuclei), as there is no myelination within the white matter before
      38 WG. The second objective is to highlight the signs highly predictive of a poor
      neurological prognosis. Lack of pontine curvature or vermian agenesis without a
      PF cyst (small volume of PF) is greatly associated with poor neurological status.
      The third objective is to propose a diagnostic strategy in difficult cases where
      prognosis is important, e.g. the Dandy Walker continuum. Analysis of the
      cerebellum is often impossible if a PF cyst is present (whatever its nature) as
      the mass effect usually blurs the foliation and even impairs evaluation of the
      normal ratio between the posterior and anterior lobes of the vermis. Isolated
      cerebellar hypoplasias raise the question of prognosis and genetic counselling.
      Such uncertainties require an amniocentesis and a careful search for other
      anomalies (cerebral and extracerebral). Unilateral abnormalities of a cerebellar
      hemisphere can be associated with good neurological status if they are isolated.
      The final objective is to discuss other rare PF fetal abnormalities, such as
      vascular malformations and tumours.

PMID- 15565346
TI  - Pituitary duplication associated with oral dermoid and corpus callosum
      hypogenesis.
AB  - We report a case of pituitary duplication in a neonate girl whose magnetic
      resonance (MR) images showed unusual findings of hypogenesis of the corpus
      callosum and oral dermoid. Pituitary duplication is an extremely rare
      malformation, with only a few previously reported cases. It occurs most commonly
      in association with complicated midline and skull base anomalies. We present a
      case of this malformation with special emphasis on the hypogenesis of splenium of
      the corpus callosum and oral dermoid.

PMID- 15565347
TI  - MR-imaging of thrombus in extra- and intracranial arteries employing balanced
      fast-field echo MRI.
AB  - Causes of stroke in young adults include a variety of disorders that are less
      frequently seen in older patients. We report the case of a young patient, who
      suffered recurrent mild embolic infarctions from a free-floating thrombus
      formation of the internal carotid artery bulb. During preoperative preparation,
      the thrombus dislodged and led to middle cerebral artery occlusion and major
      stroke. Both during preoperative work-up and after thrombus displacement balanced
      fast field echo sequences were able to demonstrate thrombus with a high signal-to
      noise ratio and a superior delineation of thrombus and flowing blood. The high
      contrast between blood and thrombus helped to establish the diagnosis, to plan
      subsequent treatment strategies and to follow closely the clinical course.
      Further studies have to show whether this technique might help in thrombus
      characterization.

PMID- 15565348
TI  - Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism
      and systemic sclerosis.
AB  - OBJECTIVES: It has been shown that exposure to some environmental toxins may
      induce scleroderma-like illness in predisposed individuals, but the
      etiopathogenesis of the idiopathic form of systemic sclerosis (SSc) remains
      obscure. The genetic background of this illness has been confirmed in multiple
      studies. We investigated whether patients with SSc differ from healthy subjects
      with regard to the enzymatic activity of polymorphic N-acetyltransferase 2
      (NAT2). METHODS: The study was carried out in 39 patients with SSc; 15 fulfilled
      the criteria of diffuse SSc (dSSc) and 24 of limited SSc (lSSc); an ethnically
      matched control group consisted of 100 healthy volunteers. Acetylation phenotype
      was estimated using the isoniazid as a model drug. The most common mutations in
      the Caucasian population at positions 481T, 803G, 590A and 857A on the NAT2 gene
      were determined using the polymerase chain reaction-restriction fragment length
      polymorphism method with deoxyribonucleic acid (DNA) extracted from peripheral
      blood. RESULTS: In the group of patients with SSc, the frequency of fast
      acetylator genotypes was 38.5% (95% CI 23.4-55.4), while that for the genotypes
      coding slow acetylator status was 51.3% (95% CI 34.8-67.6). There was a strong
      correlation between NAT2 phenotype and NAT2 genotype with a concordance of 97%.
      We did not observe a preponderance of slow acetylators among patients with SSc
      and in two subsets of SSc. With the sample size analyzed in the present study,
      there is a 90% probability of detecting significant differences in distribution
      of slow, fast, and intermediate phenotypes between patients with SSc and
      controls, there is a difference of at least 30.3, 28.7 and 21.9% in the
      distribution of these phenotypes in the general population, respectively.
      CONCLUSION: Acetylator status does not seem to be the significant factor in the
      development of SSc in patients with both subsets of this autoimmune disease, but
      further studies are required to confirm this conclusion.

PMID- 15565349
TI  - Treatment of patients with postmenopausal osteoporosis is worthwhile. The
      position of the International Osteoporosis Foundation.

PMID- 15565351
TI  - Barriers to effective management of osteoporosis in moderate and minimal trauma
      fractures: a prospective study.
AB  - Osteoporosis management is suboptimal even for high-risk people with a history of
      prior fracture. There is also evidence that individuals with moderate trauma
      fracture have a lower bone density and are at higher risk of subsequent fracture.
      This study aimed to define factors influencing the management of individuals at
      risk for osteoporosis and to examine the risk profiles of individuals with
      minimal and moderate trauma fractures. Consecutive fracture patients (n =218)
      treated in the outpatient fracture clinic in St Vincent's Hospital, Sydney, over
      a 15-month period (February 2002-July 2003) were interviewed. Fracture risk
      factors, prior investigation and treatment for osteoporosis were collected and
      participants were contacted after 3 months to ascertain follow-up. Risk factors
      for osteoporosis including family history, low dietary calcium and conditions
      associated with bone loss were similar between low- and moderate-trauma groups
      and between sexes. Even though half of participants had had a prior fracture,
      only 34% had a bone density scan and 16% were on anti-resorptive treatment. There
      was a minimal (6%) increase in the rates of investigation and treatment at the 3
      month follow-up, and less in the moderate trauma group and males. Independent
      predictors for being investigated for osteoporosis were: age over 50, prior
      fracture and female gender, while predictors for treatment were: age over 50 and
      having been investigated. This study has confirmed low rates of investigation and
      treatment even in individuals who have already suffered a prior fracture, and
      especially in those <50 and in males. People with moderate and minimal trauma
      fractures had similar risk factors for osteoporosis, including a similarly high
      proportion of prior fractures. These findings support the concept that people
      with moderate trauma fractures are at higher subsequent fracture risk, yet are
      neither investigated nor treated. This study highlights the need for further
      exploration of barriers to osteoporosis management.

PMID- 15565350
TI  - Two-year changes in bone and body composition in young children with a history of
      prolonged milk avoidance.
AB  - No previous longitudinal studies of calcium intake, anthropometry and bone health
      in young children with a history of avoiding cow's milk have been undertaken. We
      report the 2-year changes of a group of 46 Caucasian children (28 girls, l8 boys)
      aged 8.1+/-2.0 years (mean +/- SD) who had low calcium intakes at baseline and
      were short in stature, with elevated body mass index, poor skeletons and lower Z
      scores for both areal bone mineral density (BMD, in grams per square centimeter)
      and volumetric density (bone mineral apparent density, BMAD, in grams per cubic
      centimeter), compared with a reference population of milk drinkers. At follow-up,
      adverse symptoms to milk had diminished and modest increases in milk consumption
      and calcium intake had occurred. Total body bone mineral content (BMC) and bone
      area assessed by dual energy X-ray absorptiometry had increased (P<0.05), and
      calcium intake from all sources was associated with both these measures (P<0.05).
      However, although some catch-up in height had taken place, the group remained
      significantly shorter than the reference population (Z scores -0.39+/-1.14), with
      elevated body mass index (Z scores 0.46+/-1.0). The ultradistal radius BMC Z
      scores remained low (-0.31+/-0.98). The Z scores for BMD had improved to lie
      within the normal range at predominantly cortical sites (33% radius, neck of
      femur and hip trochanter) but had worsened at predominantly trabecular sites
      (ultradistal radius and lumbar spine), where values lay below those of the
      reference group (P<0.05). Similarly, although volumetric BMAD Z scores at the 33%
      radius had normalized, BMAD Z scores at the lumbar spine remained below the
      reference population at follow-up (-0.67+/-1.12, P<0.001). Our results
      demonstrate persisting height reduction, overweight and osteopenia at the
      ultradistal radius and lumbar spine in young milk avoiders over 2 years of follow
      up.

PMID- 15565352
TI  - The tale of the T-score: review and perspective.
AB  - The T-score is well known to anyone working in the field of bone densitometry. It
      is the primary output from a bone densitometry system and is most often used for
      diagnosis of osteoporosis and for making treatment decisions. Despite widespread
      acceptance of the T-score, most clinicians are unfamiliar with the historical
      evolution of the T-score as a clinical measure. Furthermore, evidence is mounting
      that the T-score is not the optimal diagnostic parameter for clinical decision
      making. Many additional risk factors have been reported which can be combined
      with bone density results to assess absolute fracture risk. This editorial
      provides an historical review of the T-score, followed by summary of the status
      of the T-score, and concludes with suggestions for the future use of the T-score
      in bone densitometry.

PMID- 15565353
TI  - Women's Health Initiative data--what were the real conclusions and how will these
      studies impact the pelvic floor?

PMID- 15565354
TI  - Isokinetic testing and endurance tests of the ankle.

PMID- 15565355
TI  - The incidence and importance of bacterial contaminants of cadaveric renal
      perfusion fluid.
AB  - Infections represent a significant risk in the postoperative transplant
      recipient. The perfusion fluid used to perfuse and preserve the kidneys prior to
      transplantation represents a potential medium in which organisms can grow. The
      aim of this study was to determine the incidence and clinical relevance of
      bacterial contamination of perfusion fluid. A total of 4 centres participated in
      the study and 269 perfusion fluid samples were taken for microbiological
      analysis. Organisms were isolated from 38 out of 218 (17.4%) perfusion fluid
      samples taken prior to allograft implantation and 23 out of 51 (45%) samples
      taken at procurement. Low virulence organisms predominated although
      Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli were also
      isolated. Although infective complications were not seen in the allograft
      recipients, given the frequency with which contamination occurs and the variation
      in unit antibiotic protocols, we recommend the routine culturing of perfusion
      fluid to ensure that any potentially significant organisms are identified and
      treated appropriately.

PMID- 15565356
TI  - Influence of ischaemia/reperfusion and LFA-1 inhibition on telomere lengths and
      CDKI genes in ex vivo haemoperfusion of primate kidneys.
AB  - The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase
      inhibitor (CDKI) genes are the markers of cell senescence and DNA damage. The aim
      of the study was to determine the influence of renal ischaemia/reperfusion (I/R)
      and anti-lymphocyte function-associated antigen-1 (LFA-1) monoclonal antibody
      (mAb) treatment on the value of the above-mentioned markers. Significantly higher
      levels of p21 and p27 were expressed by the glomeruli (P=0.001 and P=0.0001),
      tubules (P=0.0065 and P=0.0006), and interstitial cells (P=0.0017 and P=0.0022,
      respectively) of the xenoperfused kidneys. The mean T length of non-perfused
      renal specimens (5.56+/-0.60 kbp) was longer than that of the xenoperfused
      kidneys (5.46+/-0.36 kbp) [P= non-significant (NS)]. Addition of anti-LFA-1 mAb
      did not significantly influence the gene expression profile in the xenoperfused
      kidneys. The mean T length was longer in the kidneys with anti-LFA-1 mAb than in
      those without the medication (5.7+/-0.11 vs 5.13+/-0.31 kbp) (P=0.0661). Kidney
      I/R is associated with telomere shortening and an over-expression of p21 and p27
      CDKIs, which indicates substantial DNA damage and/or accelerated tissue
      senescence. Although anti-LFA-1 mAb had some protective effect on the telomeres,
      it did not influence the gene expression profile in this study.

PMID- 15565357
TI  - Why are physicians so skeptical about positive randomized controlled clinical
      trials in critical care medicine?

PMID- 15565358
TI  - Assessment of corneal epitheliopathy in the critically ill.

PMID- 15565359
TI  - Status epilepticus during acute hypercapnia: a case report.

PMID- 15565360
TI  - Active transforming growth factor-beta1 activates the procollagen I promoter in
      patients with acute lung injury.
AB  - OBJECTIVE: Fibroproliferation markers like procollagen I predict mortality in
      patients with acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from
      patients with lung injury contained mediators that would activate procollagen I
      promoter and if this activation predicted important clinical outcomes. DESIGN:
      Prospective controlled study of ALI/ARDS. SETTING: Intensive care units and
      laboratory of a university hospital. PATIENTS AND PARTICIPANTS: Acute lung
      injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis
      (positive controls) patients. INTERVENTIONS: Bronchoalveolar lavage fluid was
      collected within 48 h of intubation from ALI/ARDS patients. BALF was also
      collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema.
      Human lung fibroblasts were transfected with a procollagen I promoter-luciferase
      construct and incubated with BALF; procollagen I promoter activity was then
      measured. BALF active TGF-beta1 levels were measured by ELISA. RESULTS: Twenty
      nine ARDS patients, nine negative and six positive controls were enrolled. BALF
      from ARDS patients induced 41% greater procollagen I promoter activation than
      that from negative controls (p<0.05) and a TGF-beta1 blocking antibody
      significantly reduced this activation in ARDS patients. There was a trend toward
      higher TGF-beta1 levels in the ARDS group compared to negative controls (-1.056
      log(10)+/-0.1415 vs -1.505 log(10)+/-0.1425) (p<0.09). Procollagen I promoter
      activation was not associated with mortality; however, lower TGF-beta1 levels
      were associated with more ventilator-free and ICU-free days. CONCLUSIONS:
      Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I
      promoter, which is due partly to TGF-beta1. Activated TGF-beta1 may impact ARDS
      outcome independent of its effect on procollagen I activation.

PMID- 15565361
TI  - Characteristics and immediate outcome of childhood meningitis treated in the
      pediatric intensive care unit.
AB  - OBJECTIVE: To describe patient characteristics, use of technology and mortality
      in children with meningitis admitted to the pediatric intensive care unit (PICU).
      DESIGN: Retrospective cohort study. SETTING: Fifteen US PICUs. PATIENTS: All
      admissions with a diagnosis of meningitis between 1995 and 2000 in the Pediatric
      Intensive Care Unit Evaluations (PICUEs) database. MEASUREMENTS AND RESULTS: Of
      559 patients with meningitis, 58% were male. The median age was 19 months and the
      median length of PICU stay was 2 days. The crude PICU mortality rate was 7%.
      Three hundred thirty-four (60%) patients had bacterial meningitis. Non-survivors
      had significantly higher Pediatric Risk of Mortality (PRISM) III scores and also
      constituted a larger proportion of the patients with bacterial meningitis, coma
      and shock upon PICU admission. The use of invasive devices was higher among non
      survivors, patients with bacterial meningitis or those who were in coma or shock
      upon PICU admission. There was significant variation in the use of intracranial
      pressure (ICP) monitors by coma status and by institution. In multivariate
      analysis, patients had 1.26 higher odds of mortality for each unit increase in
      PRISM III score (odds ratio 1.26, 95% confidence interval: 1.19-1.34), while
      adjusting for other variables. CONCLUSION: In a large cohort of children admitted
      to the PICU with meningitis, severity of illness, particularly the presence of
      shock or coma, was significantly associated with both the higher use of invasive
      medical devices and higher mortality. There was significant variation in the use
      of ICP monitors among the various PICUs without statistical association with
      survival.

PMID- 15565362
TI  - Analysis of blood glucose measurements using capillary and arterial blood samples
      in intensive care patients.
AB  - OBJECTIVE: To analyse agreement between two methods for blood glucose measurement
      in intensive care patients: capillary blood using a reagent strip and glucometer
      with arterial blood using a blood gas analyser. DESIGN AND SETTING: Prospective,
      single-centre, observational study in a 12-bed tertiary referral intensive care
      unit. MEASUREMENTS: Blood glucose levels were measured in consecutive patients
      using simultaneous measurements of capillary blood samples using glucometry and
      from a multi-electrode arterial blood gas analyser. An a priori subgroup of
      patients with tissue hypoperfusion was identified (defined as systolic blood
      pressure <90 mmHg or vasopressor dependency). A total of 493 paired measurements
      were obtained; 75 of these were from patients with systemic hypoperfusion.
      RESULTS: Overall, the mean difference (bias) was 0.12 mmol/l (2.15 mg/dl) and
      precision 0.77 mmol/l (13.8 mg/dl); 95% limits of agreement were -0.14 and 1.66
      mmol/l (-2.5 and 29.8 mg/dl). In patients with systemic hypoperfusion the bias
      was 0.24 mmol/l (4.0 mg/dl) and precision 0.9 mmol/l (16.2 mg/dl); 95% limits of
      agreement -2.05 and 1.58 mmol/l (36.8 and 28.4 mg/dl). CONCLUSIONS: In a general
      population of intensive care patients, there is statistical agreement between
      blood glucose measured from capillary blood glucometry and arterial blood gas
      analysis. However, in patients with systemic hypoperfusion, the accuracy of
      agreement between these two measurement techniques may be such that that
      biochemical hypoglycaemia (<2.5 mmol/l, 44.9 mg/dl) may go undetected if used
      interchangeably.

PMID- 15565363
TI  - Returning home after intensive care: a comparison of symptoms of anxiety and
      depression in ICU and elective cardiac surgery patients and their relatives.
AB  - OBJECTIVE: This study gathered data on symptoms of anxiety and depression in
      patients and relatives after discharge from intensive care and examined whether
      the intensive care population differ from an elective cardiac surgery group with
      regards to their anxiety and depression symptom reporting. DESIGN AND SETTING: A
      single measurement point matched group comparison study in an ICU follow-up
      programme. PATIENTS AND PARTICIPANTS: Twenty ICU patients and their relatives and
      a matched comparison group of 15 elective cardiac surgery patients and their
      relatives. MEASUREMENTS AND RESULTS: Patients and relatives completed the
      Hospital Anxiety and Depression Scale. Relatives answered an open question to
      explore the perceived impact of Intensive care/cardiac surgery on their lives.
      ICU patients' relatives reported significantly higher number of symptoms of
      anxiety than did ICU patients, higher number of symptoms of depression than
      cardiac surgery patients' relatives, and more troubling and life-altering
      experiences than the relatives of cardiac surgery patients. CONCLUSIONS:
      Relatives of ICU patients also suffer anxiety and depression, and services should
      address this need. Group differences suggest that ICU patients' relatives have
      "unique" characteristics of depression symptom reporting.

PMID- 15565364
TI  - Differential effects of human atrial natriuretic peptide and furosemide on
      glomerular filtration rate and renal oxygen consumption in humans.
AB  - OBJECTIVE: Imbalance in the renal medullary oxygen supply/demand relationship can
      cause hypoxic medullary damage and ischemic acute renal failure. Human atrial
      natriuretic peptide (h-ANP) increases glomerular filtration rate in clinical
      acute renal failure. This would increase renal oxygen consumption due to
      increased tubular load of sodium. Loop diuretics are commonly used in acute renal
      failure. Data on the effects of loop diuretics on glomerular filtration rate and
      renal oxygen consumption in humans are, however, controversial. We evaluated the
      effects of h-ANP and furosemide on renal oxygen consumption, glomerular
      filtration rate, and renal hemodynamics in humans. DESIGN AND SETTING:
      Prospective two-agent interventional study in a university hospital
      cardiothoracic ICU. PATIENTS: Nineteen uncomplicated, mechanically ventilated
      postcardiac surgery patients with normal renal function. INTERVENTIONS: h-ANP (25
      and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9).
      MEASUREMENTS AND RESULTS: Renal plasma flow and glomerular filtration rate were
      measured using the infusion clearance technique for (51)Cr-labeled EDTA and
      paraaminohippurate, corrected for by renal extraction of PAH. h-ANP increased
      glomerular filtration rate, renal filtration fraction, fractional excretion of
      sodium, and urine flow. This was accompanied by an increase in tubular sodium
      reabsorption (9%) and renal oxygen consumption (26%). Furosemide infusion caused
      a 10- and 15-fold increase in urine flow and fractional excretion of sodium,
      respectively, accompanied by a decrease in tubular sodium reabsorption (-28%),
      renal oxygen consumption (-23%), glomerular filtration rate and filtration
      fraction (-12% and -7%, respectively). CONCLUSIONS: The filtered load of sodium
      is an important determinant of renal oxygen consumption. h-ANP improves
      glomerular filtration rate but does not have energy-conserving tubular effects.
      In contrast, furosemide decreases tubular sodium reabsorption and renal oxygen
      consumption and thus has the potential to improve the oxygen supply/demand
      relationship in clinical ischemic acute renal failure.

PMID- 15565365
TI  - -to: Ong KK, Petry CJ, Emmett PM et al.; ALSPAC study team (2004) Insulin
      sensitivity and secretion in normal children related to size at birth, postnatal
      growth, and plasma insulin-like growth factor-I levels. Diabetologia 47:1064
      1070.

PMID- 15565366
TI  - Mutation of the Pax6 gene causes impaired glucose-stimulated insulin secretion.

PMID- 15565367
TI  - -to: Borch-Johnsen K, Colagiuri S, Balkau B et al. (2004) Creating a pandemic of
      prediabetes: the proposed new diagnostic criteria for impaired fasting glycaemia.
      Diabetologia 47:1396-1402.

PMID- 15565368
TI  - Type 2 diabetes mellitus is associated with increased axial bone density in men
      and women from the Hertfordshire Cohort Study: evidence for an indirect effect of
      insulin resistance?
AB  - AIMS/HYPOTHESIS: Previous studies have suggested that the high bone density often
      observed in type 2 diabetic patients may be explained by insulin resistance. We
      explored this hypothesis in the Hertfordshire Cohort Study. METHODS: A total of
      465 men and 444 women aged 59 to 71 years and with no prior diagnosis of diabetes
      attended a clinic where a glucose tolerance test was performed and bone density
      measured at the femoral neck and lumbar spine. Biochemical markers of bone
      turnover (serum osteocalcin and urinary mean c-terminal cross-linking telopeptide
      of type II collagen) were measured in 163 men. RESULTS: According to WHO
      criteria, 83 men and 134 women were diagnosed with impaired glucose tolerance and
      a further 33 men and 32 women were diagnosed as having type 2 diabetes. Bone
      density was higher in newly diagnosed diabetic subjects, with relationships
      stronger in women (p<0.001) than men (p<0.05) and attenuated by adjustment for
      body mass index. In both sexes, we observed positive correlations between the
      total femur and femoral neck bone mineral density with measures of insulin
      resistance (r=0.17-0.22), with stronger results observed in women. These
      relationships did not apply after adjustment for body mass index. Glucose status
      did not lead to differences in osteocalcin level or c-terminal cross-linking
      telopeptide of type II collagen levels. CONCLUSIONS/INTERPRETATION: Our findings
      suggest that hyperinsulinaemia may affect bone mineral density through indirect
      effects, e.g. body weight.

PMID- 15565369
TI  - Tolbutamide potentiates the volume-regulated anion channel current in rat
      pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Hypoglycaemic sulphonylureas are thought to stimulate insulin
      release by binding to a sulphonylurea receptor, closing K(ATP) channels and
      inducing electrical activity. However, the fact that these drugs stimulate
      insulin release at high glucose concentrations where K(ATP) channels are closed
      suggests additional ionic actions. The aim of this study was to test the
      hypothesis that sulphonylureas influence the current of the glucose- and volume
      regulated anion channel. METHODS: Electrical and ion-channel activity were
      recorded in isolated rat beta cells using the patch-clamp technique. (86)Rb(+)
      efflux was measured using intact islets. Beta cell volume was measured using a
      video-imaging technique. RESULTS: In the absence of glucose, tolbutamide (100
      micromol/l) transiently depolarised the cells. In the presence of glucose (5
      mmol/l), tolbutamide evoked a sustained period of electrical activity, whilst at
      10 mmol/l glucose, the drug evoked a pronounced 'silent' depolarisation. In the
      absence of glucose, tolbutamide inhibited (86)Rb(+) efflux. However, at 10 mmol/l
      glucose, tolbutamide induced a transient stimulation of efflux. Tolbutamide
      potentiated the whole-cell volume-regulated anion conductance in a glucose
      dependent manner with an EC(50) of 85 micromol/l. In single channel recordings,
      tolbutamide increased the channel-open probability. Tolbutamide caused beta cell
      swelling in the presence of glucose, but not in its absence.
      CONCLUSIONS/INTERPRETATION: Tolbutamide can induce beta cell electrical activity
      by potentiating the glucose- and volume-regulated anion channel current. This
      effect is probably not due to a direct effect of the drug on the channel, but
      could be secondary to a metabolic action in the beta cell.

PMID- 15565370
TI  - IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent
      autoimmune diabetes in adults than in type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Glutamic acid decarboxylase autoantibodies (GADA) are the most
      frequent beta-cell-specific autoantibodies in type 1 diabetes and in latent
      autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet
      cells is associated with a T helper 1 cell (T(h)1) response, mainly represented
      by IgG(1)-subclass in humans. It has been proposed that the presence of IgG(4)
      may be associated with a T(h)2 response. The aim of our study was to compare the
      GADA IgG-subclass distribution between adult patients with type 1 diabetes and
      LADA. METHODS: Patients with type 1 diabetes (n=45) and patients with LADA (n=60)
      were included. Radioimmunoprecipitation assay with IgG-subclass specific
      Sepharose (IgG(1), IgG(2), IgG(3) and IgG(4)) was used to precipitate the
      antibody/antigen-complex. RESULTS: We only detected IgG(4)-subclass of GADA in
      subjects with LADA (26.7%; p<0.001). IgG(1) was the most common GADA-subclass in
      both groups, however IgG(1) as the solely expressed subclass was more common
      among type 1 diabetic patients (77.8%; p<0.05). The rank order of the frequencies
      of IgG-subclasses in type 1 diabetes was IgG(1)>IgG(3)>IgG(2)>IgG(4) and in LADA
      patients IgG(1)>IgG(4)>IgG(2)>IgG(3). CONCLUSIONS/INTERPRETATION: The difference
      in GADA IgG-subclasses could indicate a different immune response, possibly an
      altered balance between T(h)1 and T(h)2 cytokine profile in pancreatic islets.
      This difference could contribute to the slower rate of beta cell destruction in
      LADA patients, as reflected by a higher C-peptide level at clinical onset.

PMID- 15565371
TI  - The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with the
      risk of type 2 diabetes. The Ludwigshafen Risk and Cardiovascular Health study.
AB  - AIMS/HYPOTHESIS: The PlA1/A2 polymorphism of platelet glycoprotein IIIa (GPIIIa)
      has been implicated in the pathogenesis of type 2 diabetes. We studied this
      polymorphism in a homogenous, extensively phenotyped cohort using the candidate
      gene approach. METHODS: The PlA1/A2 polymorphism was determined in 1051 patients
      with type 2 diabetes and in 2247 individuals without type 2 diabetes. RESULTS: In
      patients with type 2 diabetes, genotype frequencies were as follows: PlA1/A1
      71.4%, PlA1/A2 26.0%, and PlA2/A2 2.7%. In individuals without type 2 diabetes,
      genotype frequencies were 71.6%, 25.7% and 2.8%, respectively. The PlA2 allele
      was not associated with fasting and postprandial glucose, glycated haemoglobin,
      insulin, proinsulin, C-peptide and calculated indices of insulin resistance or
      pancreatic beta cell function. The PlA2 allele was also not significantly
      associated with angiographic CHD (adjusted odds ratio [OR] 1.13; 95% CI, 0.93
      1.39) or with a history of previous myocardial infarction (adjusted OR 1.09; 95%
      CI, 0.87-1.37). CONCLUSIONS/INTERPRETATION: The GPIIIa PlA1/A2 polymorphism is
      not associated with type 2 diabetes, glucose metabolism, angiographic CHD or
      myocardial infarction.

PMID- 15565372
TI  - Diffusing capacity for carbon monoxide in children with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Few data are available on lung dysfunction in children with
      diabetes. We studied the association of pulmonary function variables (flows,
      volumes and alveolar capillary diffusion) with disease-related variables in
      children with type 1 diabetes mellitus. METHODS: We studied 39 children with type
      1 diabetes (mean age 10.9+/-2.6 years, disease duration 3.6+/-2.4 years,
      insulin.kg(-1).day(-1) 0.77+/-0.31) and 30 healthy control children (mean age
      10.4+/-3.0 years). Pulmonary function tests included spirometry, N(2) wash-out
      and the single-breath diffusing capacity for carbon monoxide (DL(CO)) corrected
      for the alveolar volume (DL(CO)/V(A)). Glycaemic control was assessed on the
      basis of HbA(1)c, with HbA(1)c values of 8% or less considered to indicate good
      glycaemic control, and HbA(1)c values of 8% or more considered to indicate poor
      control. RESULTS: Children with poor glycaemic control had comparable percentage
      values for predicted flows and volumes but lower DL(CO)/V(A) values than children
      with good glycaemic control and healthy control children (86.7+/-12.6 vs 99.8+/
      18.4 and 102.0+/-15.7; p<0.05). The predicted DL(CO)/V(A) percentages correlated
      with HbA(1)c levels (r=-0.39, p=0.013). A multiple regression analysis (stepwise
      model) controlling for HbA(1)c levels and other disease-related variables (age of
      disease onset, disease duration, daily insulin dose/kg, sex) identified HbA(1)c
      levels as the sole predictor of DL(CO)/V(A) in percent.
      CONCLUSIONS/INTERPRETATION: In children with type 1 diabetes, the diffusing
      capacity diminishes early in childhood and is associated with poor metabolic
      control. Although low DL(CO)/V(A) levels in these children probably reflect
      pulmonary microangiopathy induced by type 1 diabetes, other factors presumably
      influencing CO diffusion capacity measurements (e.g. a left shift in HbA(1)c
      resulting in high O(2) binding and low CO binding) could explain the apparent
      capillary and alveolar basal membrane dysfunction.

PMID- 15565373
TI  - Metformin or gliclazide, rather than glibenclamide, attenuate progression of
      carotid intima-media thickness in subjects with type 2 diabetes.
AB  - AIM/HYPOTHESIS: Metformin is a well-known oral hypoglycaemic agent and has been
      commonly used, in combination with sulphonylurea, to treat type 2 diabetes.
      However, the advantageous effect of metformin plus sulphonylurea on diabetic
      macroangiopathy has yet to be clarified. To evaluate whether sulphonylurea or
      sulphonylurea plus metformin prevent diabetic macroangiopathy, we examined the
      progression of carotid artery intima-media thickness (IMT) as a surrogate end
      point. METHODS: Subjects with type 2 diabetes were divided into three groups,
      receiving the following treatments: (i) glibenclamide (n=59); (ii) gliclazide
      (n=30); and (iii) glibenclamide + metformin (n=29). Maximum IMT and average IMT
      (the greatest value among 6 average values of each 3 points including greatest
      thickness) were measured at the beginning and end of the observation period.
      RESULTS: For the follow-up period of 3 years, the annual change in average IMT of
      the glibenclamide plus metformin group (0.003+/-0.048 mm) was smaller than that
      of the glibenclamide group (0.064+/-0.045 mm) and gliclazide group (0.032+/-0.036
      mm) (p<0.0001 and p=0.043 respectively). In the gliclazide group, average IMT
      increased during the follow-up period, but annual change in average IMT was
      significantly smaller than that of the glibenclamide group (p=0.005).
      Glibenclamide + metformin or gliclazide also attenuated the progression of
      maximum IMT, compared with that of glibenclamide (0.041+/-0.105, 0.044+/-0.106,
      0.114+/-0.131 mm/year respectively, p=0.029 and p=0.035 respectively).
      Multivariable regression analysis implied that administration of metformin or
      gliclazide significantly and independently (p<0.05) reduces the progression of
      average IMT, compared with glibenclamide monotherapy. CONCLUSIONS/INTERPRETATION:
      These data indicate that metformin or gliclazide, rather than glibenclamide, have
      a potent anti-atherogenic effect in type 2 diabetes.

PMID- 15565374
TI  - Reduction of beta cell mass: partial insulin secretory compensation from the
      residual beta cell population in the nicotinamide-streptozotocin Gottingen
      minipig after oral glucose in vivo and in the perfused pancreas.
AB  - AIMS/HYPOTHESIS: A progressive loss of beta cell function and mass are important
      contributory factors in the development and progression of type 2 diabetes. The
      aim of this study was to evaluate the effects of a primary reduction in beta cell
      mass on beta cell function in vivo and in the perfused pancreas and to relate
      these characteristics to beta cell mass. METHODS: The beta cell mass of six
      Gottingen minipigs was reduced chemically (using 67 mg/kg nicotinamide and 125
      mg/kg streptozotocin). Six untreated minipigs were kept as control animals.
      Insulin responses were evaluated in vivo using the mixed meal tolerance test (2
      g/kg oral glucose) and in the isolated perfused pancreata from the same animals
      by stimulation with glucose, glucagon-like peptide-1 or arginine. RESULTS: Beta
      cell mass was reduced in the beta-cell-reduced animals compared with the control
      minipigs (182+/-76 vs 464+/-156 mg, p<0.01). AUC(glucose) was increased in the
      beta-cell-reduced animals (1383+/-385 vs 853+/-113 mmol.l(-1).min in control
      minipigs, p<0.01), as was the insulin response to oral glucose per unit of beta
      cell mass (123+/-84 vs 56+/-24 pmol.l(-1).min.mg(-1), p<0.05). Total in vitro
      insulin secretion was increased per unit of beta cell mass in nicotinamide +
      streptozotocin pancreata compared to controls (83.7+/-45.9 vs 34.6+/-14.4 nmol/mg
      beta cells, p<0.05) with responses to glucose and glucagon-like peptide-1 showing
      a partial compensation for reduced beta cell mass, whereas no compensation was
      seen in response to arginine. CONCLUSIONS/INTERPRETATION: A primary reduction in
      beta cell mass impairs glucose tolerance and leads to a compensatory increase in
      insulin secretion from the remaining beta cells after oral glucose in vivo, which
      is even more apparent in the perfused pancreas. It remains to be determined
      whether this compensation can be maintained in the long term.

PMID- 15565375
TI  - High-sensitivity C-reactive protein and impaired coronary vasoreactivity in young
      men with uncomplicated type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Elevated high-sensitivity C-reactive protein (hsCRP)
      concentrations indicate increased risk of future coronary events. The association
      between hsCRP and coronary vasoreactivity has not yet been examined in type 1
      diabetic subjects. METHODS: We studied 18 young men who were non-smokers and who
      had uncomplicated type 1 diabetes. The diabetic subjects were divided into two
      groups, according to their median hsCRP concentration, as follows: (i) subjects
      with slightly elevated hsCRP (median 0.76 mg/l, range 0.47-4.73 mg/l, n=8); and
      (ii) subjects with low hsCRP (median 0.32 mg/l, range 0.11-0.35 mg/l, n=10). In
      addition we investigated 22 non-diabetic age-matched subjects (hsCRP: median 0.42
      mg/l, range 0.11-1.31 mg/l). Resting myocardial blood flow and hyperaemic
      adenosine-stimulated flow during euglycaemic-hyperinsulinaemic clamp were
      determined using positron emission tomography and oxygen-(15)-labelled water.
      RESULTS: Diabetic subjects with slightly elevated hsCRP had significantly higher
      hsCRP concentrations than non-diabetic subjects (p=0.008). Resting myocardial
      blood flow was similar (NS) in diabetic subjects with slightly elevated hsCRP
      (0.79+/-0.19 ml.g(-1).min(-1)) or low hsCRP (0.81+/-0.15 ml.g(-1).min(-1)) and
      non-diabetic subjects (0.80+/-0.19 ml.g(-1).min(-1)). Adenosine infusion induced
      a significant increase in blood flow in all study subjects (p<0.001) but was
      blunted in diabetic subjects with slightly elevated hsCRP (3.42+/-0.61 ml.g(
      1).min(-1)) when compared with diabetic subjects with low hsCRP (5.08+/-1.65
      ml.g(-1).min(-1), p=0.02) or non-diabetic subjects (4.51+/-1.36 ml.g(-1).min(-1),
      p=0.04). Adenosine-stimulated flow was inversely correlated with hsCRP
      concentrations in all diabetic subjects (r=-0.70, p=0.001).
      CONCLUSIONS/INTERPRETATION: In young subjects with uncomplicated type 1 diabetes,
      even slightly elevated hsCRP concentrations are associated with reduced coronary
      vasoreactivity.

PMID- 15565376
TI  - Genetic basis of barley caryopsis dormancy and seedling desiccation tolerance at
      the germination stage.
AB  - The genomic regions controlling caryopsis dormancy and seedling desiccation
      tolerance were identified using 152 F4 lines derived from a cross between Mona, a
      Swedish cultivar, and an Israeli xeric wild barley Hordeum spontaneum genotype
      collected at Wadi Qilt, Israel. Dormancy, the inability of a viable seed to
      germinate, and desiccation tolerance, the ability of the desiccated seedlings to
      revive after rehydration, were characterized by fitting the germination and
      revival data with growth curves, using three parameters: minimum, maximum, and
      slope of germination or revival rate derived by the least square method. The
      genetic map was constructed with 85 genetic markers (SSRs, AFLPs, STSs, and Dhn
      genes) using the MULTIPOINT: -mapping algorithm. Quantitative trait loci (QTLs)
      mapping was conducted with the MULTIQTL: package. Ten genomic regions were
      detected that affected the target traits, seven of which affected both dormancy
      and desiccation tolerance traits. Both the wild barley genotype and the Swedish
      cultivar contributed the favorite alleles for caryopsis dormancy, whereas
      seedling desiccation tolerance was attributed to alleles descending from the
      cultivar. The results indicate that some barley dormancy genes are lost during
      domestication and that dormancy QTLs are associated with abiotic stress
      tolerance.

PMID- 15565377
TI  - Inheritance of seed colour and identification of RAPD and AFLP markers linked to
      the seed colour gene in rapeseed (Brassica napus L.).
AB  - In China Polima cytoplasmic male sterility (cms) is currently the most important
      hybrid system used for the breeding of hybrids. In an effort to develop yellow
      seeded Polima cms restorer lines, we used yellow-seeded, doubled haploid (DH)
      line No.2127-17 as the gene source in crosses with two elite black-seeded Polima
      cms R lines, Hui5148-2 and 99Yu42, which originated from our breeding programme.
      The inheritance of seed colour was investigated in the F2, BC1 and F1-derived DH
      progenies of the two crosses. Seed colour was found to be under the control of
      the maternal genotype and the yellow seed trait to be partially dominant over the
      black seed trait. Segregation analysis revealed a single gene locus for the
      partial dominance of yellow seed colour. Of 810 randomly amplified polymorphic
      DNA (RAPD) primers, 240 (29.6%) revealed polymorphisms between the parents. Of
      the 240 RAPD primers and 512 amplified fragment length polymorphism (AFLP) primer
      pairs, four RAPDs and 16 AFLP pairs showed polymorphisms between the bulks, with
      two RAPD and eight AFLP markers being identified in the vicinity of the seed-coat
      colour gene locus using a DH progeny population-derived from the cross Hui5148
      2xNo.2127-17-of 127 individuals in combination with the bulked segregant analysis
      strategy. Seven of these latter ten markers were linked to the allele for yellow
      seed, whereas the other three were linked to the allele for black seed. The seed
      coat colour gene locus was bracketed by two tightly linked markers, EA02MG08 (2.4
      cM) and S1129 (3.9 cM). The partial dominance and single gene control of the
      yellow seed-coat colour trait together with the available molecular markers will
      greatly facilitate the future breeding of yellow-seeded hybrid varieties.

PMID- 15565378
TI  - The potato P locus codes for flavonoid 3',5'-hydroxylase.
AB  - The potato P locus is required for the production of blue/purple anthocyanin
      pigments in any tissue of the potato plant such as tubers, flowers, or stems. We
      have previously reported, based on RFLP mapping in tomato, that the gene coding
      for the anthocyanin biosynthetic enzyme flavonoid 3',5'-hydroxylase (f3'5'h) maps
      to the same region of the tomato genome as P maps in potato. To further evaluate
      this association a Petunia f3'5'h gene was used to screen a potato cDNA library
      prepared from purple-colored flowers and stems. Six positively hybridizing cDNA
      clones were sequenced and all appeared to be derived from a single gene that
      shares 85% sequence identity at the amino acid level with Petunia f3'5'h. The
      potato gene cosegregated with purple tuber color in a diploid F1 sub-population
      of 37 purple and 25 red individuals and was found to be expressed in tuber skin
      only in the presence of the anthocyanin regulatory locus I. A potato f3'5'h cDNA
      clone was placed under the control of a doubled CaMV 35S promoter and introduced
      into the red-skinned cultivar 'Desiree'. Tuber and stem tissues that are colored
      red in Desiree were purple in nine of 17 independently transformed lines.

PMID- 15565379
TI  - Demonstration of linkage and development of the first low-density genetic map of
      garlic, based on AFLP markers.
AB  - Garlic (Allium sativum L.) is a long-cultivated, clonally propagated diploid
      plant (2n=2x=16). With routine seed production now underway, we used populations
      (MP1 and MP2) generated by self-pollination of unrelated plants to generate two
      low-density genetic maps of garlic, consisting of amplified fragment length
      polymorphism (AFLP) and gene-specific markers. We did not observe any two plants
      with identical marker patterns in either population, indicating that they were
      the result of amphimixis rather than apomixis. This is an important finding,
      since several Alliums are facultative apomicts. A total of 360 markers segregated
      in MP1 (12.8 AFLP markers per primer combination) and 321 markers segregated in
      MP2 (13.9 per primer combination) to indicate a fairly high level of genetic
      heterozygosity in the garlic nuclear genome. Of these markers, 15.3% in MP1 and
      24.3% in MP2 had segregation ratios distorted from the expected 3:1.
      Interestingly, 94.7% of those distorted segregations fit a 15:1 segregation ratio
      for duplicated loci, suggesting extensive levels of duplication in the garlic
      genome and supporting similar observations for onion. The genetic map for the MP1
      family with 216 markers spanned 1,166 cM of the garlic genome (5.4 cM average),
      while 143 markers of MP2 spanned 862 cM (6.0 cM average). Gene-specific markers
      for alliinase, chitinase, sucrose 1-fructosyltransferase (SST-1), and chalcone
      synthase (CHS) were mapped, demonstrating the immediate utility of the garlic
      genetic map. These two garlic families had relatively few segregating AFLP
      markers in common, which supports their relatively distant relationship based on
      diversity analysis. Of those markers that were conserved, linkages were also
      conserved.

PMID- 15565382
TI  - [Contrast-enhanced sonography of the liver].
AB  - The detection rate of liver lesions using ultrasonography is 53-77%, rendering
      this method inferior to CT and MRI. Despite well-known limitations, development
      of stable second-generation contrast agents in conjunction with new techniques of
      contrast display has led to increased diagnostic accuracy. Characterization of
      focal liver lesions with ultrasound contrast agents follows known features of
      iodine- and gadolinium-containing contrast agents, but compared to CT and MRI
      sensitive visualization of intratumoral vessels takes place in real time. In
      addition to very high diagnostic accuracy in differentiating benign from
      malignant lesions, detectability of tumors of nonhepatocellular origin is
      increased significantly and direct assessment of treatment success with minimally
      invasive tumor ablative interventions in the liver is possible. The active
      principle of ultrasound contrast agents, examination technique as well as
      distinguishing features and appearance of various, frequently observed focal
      liver lesions are illustrated by cases from our department.

PMID- 15565383
TI  - [Interferon therapy of multiple sclerosis. Synopsis of various dosage forms].
AB  - In addition to the clinical efficacy, which is similar for the three approved
      interferon-beta preparations, the compliance and acceptance of interferon therapy
      are determined by several other factors. These include the mode of application,
      formulation, storing conditions, and injection methods. Some of these factors
      have been modified recently. In this article we provide a synopsis of the current
      application formats of the different interferon-beta preparations, and discuss
      the respective advantages and drawbacks.

PMID- 15565384
TI  - Regulation of sexual development in the basal termite Cryptotermes secundus:
      mutilation, pheromonal manipulation or honest signal?
AB  - Social insect colonies are not the harmonious entities they were once considered.
      Considerable conflicts exist between colony members, as has been shown for
      Hymenoptera. For termites, similar studies are lacking, but aggressive
      manipulations have been claimed to regulate sexual development, and even to
      account for the evolution of workers. This study on a basal termite, Cryptotermes
      secundus (Kalotermitidae), suggests that the importance of aggressive
      manipulations in termites has been overemphasized. Wing-bud mutilations, a means
      proposed to regulate the development of dispersing sexuals (alates), seem to be
      artifacts of handling conditions that cause disturbance. Aggressive behaviors
      never occurred unless colonies were disturbed. Theoretical considerations further
      showed that the potential for intense conflict among termite nestmates is low
      compared to hymenopteran societies. Strong conflicts are only expected to occur
      over the replacement of natal reproductives that died, while less intense
      conflicts should exist over the development into alates when food in the colony
      becomes limiting. Accordingly, intracolonial aggressive interactions over
      replacement are common, whereas nestmates seem to manipulate alate development
      via proctodeal feeding when food resources decline. However, the latter is rather
      an honest signal than a manipulation because only the most competent prospective
      dispersers can impede the development of nestmates.

PMID- 15565386
TI  - [Application of the pelvic C-clamp].
AB  - Unstable pelvic girdle injury combined with severe pelvis related haemorrhage has
      a high mortality rate. This prognosis can be improved by using the C-clamp
      according to Ganz. This can be applied while the life saving measures are in
      progress, and should, if necessary, be combined with a pelvic tamponade. Due to
      the limited number of patients, trauma centres have the most experience with this
      technique. In this contribution, we present our standardised application
      technique, which allows the use of the procedure through well defined clinically
      recognisable orientation points in the emergency room.

PMID- 15565387
TI  - [Total intravenous anesthesia with propofol and remifentanil. Results of a
      multicenter study of 6,161 patients].
AB  - INTRODUCTION: The aim of this study was to investigate efficacy and tolerability
      of propofol, remifentanil and cisatracurium or mivacurium in routine anesthetic
      practice. PATIENTS AND METHODS: A total of 6,161 patients scheduled for abdominal
      or orthopedic surgery were included in this open multicenter phase IV study.
      Perioperative hemodynamics as well as induction, recovery and discharge times,
      anesthetics, frequency of PONV and side-effects were studied. RESULTS: Quality of
      induction and maintenance of anesthesia were evaluated by anesthesiologists to be
      good or very good in 88%. 86% of the patients assessed anesthesia as good or very
      good. Adverse events were reported for 28 patients (0.45%), with hypotension and
      bradycardia being most frequent. Recovery was evaluated by anesthesiologists to
      be good or very good in 88%, surgeons and nursing staff assessed the TIVA as good
      or very good in 90%. Most frequent postoperative complaints were pain (16.7%),
      nausea (6.1%), shivering (3.1%) and vomiting (0.7%). CONCLUSIONS: The study
      showed that total intravenous anesthesia using propofol, remifentanil and
      cisatracurium or mivacurium is safe, tolerable and effective and has a high
      degree of acceptance.

PMID- 15565388
TI  - [Evidence-based intensive care treatment of intracranial hypertension after
      traumatic brain injury].
AB  - Traumatic brain injury (TBI) occurs frequently and is associated with a poor
      prognosis. Severe TBI results in substantial disability or death in more than 40%
      of cases. The major aim of treatment of these patients is to minimize secondary
      brain injury and in this respect, the prevention of intracranial hypertension
      plays a key role. In addition to surgical approaches, various conservative
      treatment options exist, such as the use of osmodiuretics, barbiturates, or
      corticosteroids, hyperventilation as well as induced therapeutic hypothermia.
      This review analyzes these treatment options and the therapeutic goals of
      lowering intracranial pressure (ICP) in patients after TBI using evidence-based
      criteria, and provides recommendations for clinical practice.

PMID- 15565392
TI  - p-ANCA-associated periaortitis with histological proof of Wegener's
      granulomatosis: case report.
AB  - We describe a 63-year-old man who presented with an inflammatory aortic aneurysm.
      The patient had p-ANCA antibodies directed against myeloperoxidase. A diagnosis
      of idiopathic periaortitis was made. Seven years later, he was rehospitalized
      because of fever, weight loss, and polyneuropathy. After revision of the aortic
      biopsy, which showed necrotizing vasculitis with palisading granuloma, a
      diagnosis of Wegener's granulomatosis (WG) was made. This case report illustrates
      an unusual disease course in WG, resembling large vessel vasculitis, and we
      discuss the possible mechanisms of large vessel involvement in this form of
      vasculitis.

PMID- 15565393
TI  - Debilitating diarrhoea and weight loss due to colitis in two RA patients treated
      with leflunomide.
AB  - Diarrhoea and weight loss are frequently reported adverse events in rheumatoid
      arthritis (RA) patients receiving the disease-modifying antirheumatic drug
      (DMARD) leflunomide. According to the available literature these side effects
      occur mostly during the first 6 months of treatment, are rather mild and rarely
      lead to treatment withdrawal. In this report, we describe the clinical,
      endoscopic and histologic findings in two RA patients with severe diarrhoea and
      important weight loss more than 12 months after starting treatment with
      leflunomide. In both cases the symptoms were caused by colitis, but one had
      ulcerative and the other microscopic colitis. Despite treatment with budesonide
      the complaints only improved after withdrawal of leflunomide, making a causal
      relationship between this drug and the pathogenesis of colitis probable. The
      heterogeneous histopathological findings in these two patients, however, do not
      allow us to draw any definitive conclusions about the mechanism by which
      leflunomide causes diarrhoea and weight loss in RA patients. We conclude that
      persistent diarrhoea or weight loss in patients taking leflunomide can be more
      serious than what is previously reported in the literature. In such cases
      leflunomide treatment should be stopped and an endoscopic examination of the
      colon is recommended. Given the long half-life of this drug a washout procedure
      with cholestyramine should be considered whenever the problem is severe or
      persistent.

PMID- 15565394
TI  - Clinical significance of von Willebrand factor in patients with adult
      dermatomyositis.
AB  - Because the clinical significance of von Willebrand factor (vWF), a marker of
      endothelial injury, has not been well studied in adult patients with
      dermatomyositis (DM), we evaluated whether plasma vWF levels are useful as an
      index of disease activity in these patients. We measured plasma vWF antigen
      levels in 11 patients with active adult DM, 13 patients with inactive DM, and 18
      healthy subjects using an enzyme-linked immunosorbent assay. The association of
      vWF level with clinical condition and muscle-derived enzyme leakage among DM
      patients was examined using analysis of covariance and logistic regression
      analysis. Furthermore, we studied the effects of treatment on the vWF antigen
      level. The mean vWF antigen level was significantly higher in active DM patients
      than in inactive DM patients and healthy subjects. Higher vWF levels were
      associated with clinical symptoms, such as general fatigue, fever, and muscle
      weakness. They were also associated with the levels of aspartate
      aminotransferase, alanine aminotransferase, and aldolase, but not with those of
      lactate dehydrogenase and creatine kinase (CK). vWF antigen was correlated with
      muscle enzymes except for CK. The plasma vWF levels in six patients with active
      DM significantly decreased after successful corticosteroid treatment. Plasma vWF
      level may be considered a useful marker of disease activity in adult DM patients.

PMID- 15565395
TI  - Systemic lupus erythematosus arising during interferon-alpha therapy for
      cryoglobulinemic vasculitis associated with hepatitis C.
AB  - We present the case of a 53-year-old woman who developed systemic lupus
      erythematosus (SLE) after being treated with interferon-alpha (IFN-alpha) for
      cryoglobulinemic vasculitis associated with hepatitis C virus (HCV) infection.
      Her cryoglobulinemic vasculitis resolved rapidly with IFN-alpha treatment.
      However, after 10 months of IFN-alpha therapy, she developed a photosensitive
      malar rash, oral ulcers, arthralgias, lymphopenia, and anti-SSA autoantibodies.
      She was diagnosed with SLE induced by IFN-alpha therapy. IFN-alpha was
      discontinued, she was treated with a short course of prednisone and
      hydroxychloroquine, and she improved rapidly. This is the first report of IFN
      alpha-induced SLE complicating treatment of cryoglobulinemic vasculitis
      associated with HCV infection. The development of SLE during therapy with IFN
      alpha could be due to direct immunomodulation by IFN-alpha, and review of
      experimental data and prior case reports suggests a pathogenic role for IFN-alpha
      in SLE.

PMID- 15565396
TI  - Electric shock wave lithotripsy (ESWL) as a pain control measure in
      dermatomyositis with calcinosis cutis-old method, new discovery.
AB  - A 23-year-old Chinese man with dermatomyositis associated calcinosis cutis
      received electric shock wave lithotripsy (ESWL) as an alternate to a conventional
      pharmacological regimen to reduce pain associated with the complications of
      subcutaneous calcinosis nodules. He became symptom and opioid free after two
      courses of ESWL. No significant adverse effect had been noted. ESWL may serve as
      a means of pain killing in patients suffering from debilitating pain caused by
      complicated calcinosis cutis.

PMID- 15565397
TI  - A missense mutation in the coiled-coil motif of the HP1-interacting domain of ATR
      X in a family with X-linked mental retardation.

PMID- 15565398
TI  - The relationship between gastroesophageal reflux disease and obstructive sleep
      apnea.
AB  - There has been an accumulating body of research concerning the extraesophageal
      complications of gastroesophageal reflux disease over the past decade. Given the
      cardiological, pulmonological, laryngeal, and dental aspects of such
      complications, an interdisciplinary approach is required. The most recognized
      manifestations are noncardiac chest pain, bronchial asthma, chronic bronchitis,
      chronic cough, and posterior laryngitis, as well as the acidic damage of dental
      enamel. This article focuses on the potential relationship between reflux disease
      and obstructive sleep apnea, which has been raised only more recently. Because of
      the decrease of primary peristalsis and the reduced production of saliva, as well
      as the diminished acid and volume clearance of the esophagus, sleeping can be
      considered as a risk factor of the reflux event by itself. Moreover, it should
      also be taken into account that the transdiphragmatic pressure increases in
      parallel with the growing intrathoracic pressure generated during obstructive
      apnea episodes. This has a non-negligible effect on the phrenoesophageal
      ligament, which is connected to the lower esophageal sphincter. Repetition of the
      pressure changes results in insufficiency of the cardia. While this pressure
      change produces a considerable suction effect, further reducing the clearing
      mechanism of the gastric volume, lower esophageal sphincter insufficiency can
      directly lead to reflux disease. The challenge for gastroenterologists is to gain
      further insight into this relationship and to play a more active role in the
      complex therapy of the disease, as well as to develop a new diagnostic approach
      towards the severe forms of gastroesophageal reflux disease.

PMID- 15565399
TI  - Effect of Helicobacter pylori infection on intragastric acidity in patients with
      reflux esophagitis.
AB  - BACKGROUND: The effect of Helicobacter pylori infection on intragastric acidity
      in patients with reflux esophagitis was investigated. METHODS: Esophageal
      motility and 24-h intragastric acidity were assessed in endoscopy-proven reflux
      esophagitis patients with ( n = 50) and without ( n = 50) H. pylori infection.
      RESULTS: Most of the patients had a mild degree of esophagitis. There was no
      difference in the age, sex, or body mass index (BMI) between patients with and
      without H. pylori infection. The 24-h intragastric pH monitoring showed less
      acidity in patients with H. pylori infection than in those without H. pylori
      infection (median pH, 1.6 +/- 0.3 vs 1.4 +/- 0.1, with vs without H. pylori
      infection; P < 0.01). No difference in the patterns of esophageal motility
      dysfunction was noted between these two groups of patients. CONCLUSIONS: Patients
      with reflux esophagitis and H. pylori infection had less intragastric acidity
      than those without H. pylori infection. However, the extent of acid suppression
      was insufficient to protect the esophagus from acid injury. In addition, the
      degree of esophageal motility dysfunction was similar in both groups. Therefore,
      H. pylori infection may play no role in the pathogenesis of reflux esophagitis.

PMID- 15565400
TI  - Effect of Helicobacter pylori eradication in the treatment of Japanese patients
      with chronic idiopathic urticaria.
AB  - BACKGROUND: Infection with Helicobacter pylori has been associated with chronic
      idiopathic urticaria (CIU). The aim of this study was to investigate the efficacy
      of H. pylori eradication in the treatment of patients with CIU. METHODS: Fifty
      patients with CIU (16 men and 34 women; age 25-75 years) and 100 sex- and age
      matched control subjects were enrolled in the study. Presence of IgG antibody to
      H. pylori was examined by serology. H. pylori-seropositive patients with CIU
      received endoscopy to confirm H. pylori infection. Patients infected with H.
      pylori received eradication therapy comprising lansoprazole, amoxicillin, and
      either clarithromycin or metronidazole. At least 2 months after finishing the
      eradication therapy, a (13)C-urea breath test was performed, and the effect of
      eradication therapy on the CIU was scored, using a three-point scale, as complete
      remission, partial remission, or no improvement. RESULTS: In the 50 patients with
      CIU, 26 (52%) were H. pylori-seropositive, while 48% (48/100) of the control
      subjects were seropositive (statistically not significant). Nineteen out of the
      26 patients with CIU infected with H. pylori received eradication therapy, and
      eradication was successful in 17 patients. In the 17 H. pylori-eradicated
      patients, 6 (35%) had complete remission and 11 (65%) had complete remission or
      partial remission. On the other hand, in the 9 patients without H. pylori
      eradication, only 2 (22%) showed partial remission and 7 (78%) had no
      improvement. CONCLUSIONS: Eradication of H. pylori would be a valid choice for
      patients with CIU, although the prevalence of H. pylori infection is not higher
      in patients with CIU than it is in controls.

PMID- 15565401
TI  - The protective and hormonal effects of proanthocyanidin against gastric mucosal
      injury in Wistar rats.
AB  - BACKGROUND: Proanthocyanidin, a grape-seed polyphenol, has been reported to have
      protective properties against vascular injury and ulcers, preventive effects
      against atherosclerosis and cancer, and antioxidative effects, such as improving
      lipid metabolism and slowing aging. However, little has been reported on its
      antiulcer effects. We aimed to elucidate the antiulcer mechanism of
      proanthocyanidin. METHODS: Gravinol, containing 89.3% proanthocyanidin, was used.
      Proanthocyanidin solution, in distilled water, at 0.002%, 0.02%, 0.2%, or 1%, was
      given to rats ad libitum for 2 weeks. Distilled water was given to control rats.
      The effect of proanthocyanidin on gastric mucosal injury was investigated with
      the water-immersion restraint stress model. The ratios of areas of hemorrhagic
      erosion were compared as the lesion index. Myeloperoxidase activities were also
      examined, as an index of tissue injury. Superoxide dismutase activity was
      measured to examine its antioxidative effect. Furthermore, serum gastrin,
      somatostatin, histamine, and prostaglandin E(2) levels were measured in this rat
      model. RESULTS: Proanthocyanidin administration significantly suppressed gastric
      mucosal injury, induced by water-immersion restraint stress, in a dose-dependent
      manner. Myeloperoxidase activities were also significantly inhibited, whereas
      superoxide dismutase activities were significantly stimulated. As to
      gastrointestinal hormones, the secretion of gastrin, somatostatin, and histamine
      was significantly inhibited, while prostaglandin E(2) secretion was significantly
      stimulated. CONCLUSIONS: Proanthocyanidin was shown to have a protective effect
      on the gastric mucosa. The mechanisms underlying the effect of proanthocyanidin
      were considered to be the following: anti-gastrin and anti-histamine effects to
      prevent attacks by water-immersion restraint stress, and mucoprotective
      properties, bestowed by increased prostaglandin and increased superoxide
      dismutase activities in the gastric mucosa.

PMID- 15565402
TI  - Results of triple eradication therapy in Japanese children: a retrospective
      multicenter study.
AB  - BACKGROUND: Large-scale clinical trials in children are lacking concerning
      Helicobacter pylori eradication therapies. The purpose of this study was to
      assess the efficacy of proton pump inhibitor (PPI)-based triple therapies in
      Japanese children. METHODS: This was a retrospective analysis of the first- and
      second-line PPI-based triple therapies from pediatric gastrointestinal units
      between 1996 and 2003. Data collected included doses and duration of regimens,
      drug compliance, success or failure of eradication, ulcer healing, and symptom
      response of those with dyspepsia and no ulcers. The results of antibiotic
      susceptibility tests were also reported in cases where these were performed.
      RESULTS: A total of 149 pediatric patients (mean age, 12.6 years) were studied,
      including 123 patients who received first-line therapy: 115 received a PPI plus
      amoxicillin and clarithromycin (PAC) and 8 received a PPI plus amoxicillin and
      metronidazole (PAM). Overall eradication rates of the first-line PAC and PAM
      therapies were 77.4% and 87.5%, respectively ( P = 0.68). All 14 patients with
      failed PAC therapy received the second-line PAM regimen, resulting in an
      eradication rate of 100%. Mild side effects were reported only in PAC regimens
      (13.8%). Primary resistance to amoxicillin, clarithromycin, and metronidazole was
      detected in 0%, 34.7%, and 12.5% of the strains, respectively. The PAC regimen
      showed a high eradication rate for clarithromycin-susceptible strains (91.7%),
      but was relatively ineffective for resistant strains (40.0%) ( P < 0.01).
      Eradication of H. pylori was associated with ulcer healing and symptomatic
      improvement among those with gastritis only (both; P < 0.001). Among 17 patients
      with iron-deficiency anemia, post-treatment hemoglobin levels were higher than
      the pretreatment levels ( P < 0.001). CONCLUSIONS: The PAC regimen is effective
      in children. Clarithromycin resistance is associated with eradication failure.
      Metronidazole is a good substitute for clarithromycin as the second-line option
      for children.

PMID- 15565403
TI  - Infection with hepatitis B virus genotype A in Tokyo, Japan during 1976 through
      2001.
AB  - BACKGROUND: Because genotype A of hepatitis B virus (HBV) is not indigenous,
      there have been only few data on infection with it in Japan. METHODS: We examined
      clinical and virological features of the 66 Japanese patients who admitted
      Toranomon Hospital in Tokyo, Japan, between 1976 and 2001, who were found to have
      HBV/A infection. HBV genotype A was classified into subtype A (European type) and
      A' (South African type) by phylogenetic analysis of the preS1 and preS2 regions,
      and the S gene sequences. RESULTS: Of the 66 patients infected with HBV/A, 14
      (21%) were asymptomatic carriers, 26 (39%) presented with acute hepatitis, 22
      (33%) with chronic hepatitis, and 4 (6%) with liver cirrhosis. HBV/A infection
      persisted for more than 6 months in 5 of the 26 (19%) patients with acute
      hepatitis. The frequency of acute hepatitis in patients infected with HBV/A was
      higher after than before 1991 (2/22 [9%] vs 24/44 [55%]; P < 0.0001). The
      frequency of nucleotide 1858 of T was higher in asymptomatic carriers than in
      patients with acute hepatitis in whom infection was resolved (5/14 [36%] vs 0/21
      [0%]; P = 0.008). Of the 57 patients for whom subtypes of genotype A were
      determined, subtype A was identified in 53 (93%) and subtype A' in only 4 (7%).
      All patients infected with subtype A' were persistently infected with HBV.
      CONCLUSIONS: HBV/A infection has become more frequent during recent years,
      predominantly presenting as acute hepatitis, and subtype A' is uncommon in the
      Tokyo metropolitan area.

PMID- 15565404
TI  - Induction and maintenance of anti-HBs in immunosuppressed murine hepatitis B
      virus carriers by a novel vaccination approach: implications for use in hepatitis
      B virus-infected subjects with liver transplantation.
AB  - BACKGROUND: One of the major problems with orthotopic liver transplantation (OLT)
      in patients with endstage liver diseases due to hepatitis B virus (HBV) is to
      maintain sustained high levels of antibody to hepatitis B surface antigen (anti
      HBs) to block reactivation of HBV infection and allograft rejection. The aim of
      this study was to induce anti-HBs by a unique vaccination protocol, using
      hepatitis B surface antigen (HBsAg)-pulsed dendritic cells (DCs) in
      immunosuppressed murine HBV carriers. METHODS: Immunosuppressed murine HBV
      carriers were produced by injecting FK-506 (2 mg/kg), intraperitoneally, daily
      for 15 days in HBV-transgenic mice (Tg) expressing HBV-related mRNAs and
      proteins. HBsAg-pulsed DCs were prepared by culturing murine spleen DCs with
      HBsAg (100 microg) for 24 h. HBsAg-pulsed DCs were injected twice, at an interval
      of 2 weeks, to immunosuppressed HBV-Tg and the levels of anti-HBs were measured
      periodically for 4 months. RESULTS: Injection with FK-506 resulted in the
      production of immunosuppressed HBV-Tg, as evident by their low production of
      cytokine mRNAs and proteins. Two injections of HBsAg-pulsed DCs from
      immunosuppressed HBV-Tg induced anti-HBs in all immunosuppressed HBV-Tg within 4
      8 weeks after the second injection. More than 10 IU/l of anti-HBs was detected in
      the sera in all but one immunosuppressed HBV-Tg for more than 4 months, although
      all immunosuppressed HBV-Tg were continuously provided with FK-506 on a daily
      basis for the entire duration of the study. CONCLUSIONS: The capacity of HBsAg
      pulsed DCs to induce anti-HBs in immunosuppressed HBV-Tg inspires optimism for
      the possible use of this therapeutic regimen for HBV-infected OLT patients.

PMID- 15565405
TI  - Influence of TNF gene polymorphism in patients with acute and fulminant
      hepatitis.
AB  - BACKGROUND: Tumor necrosis factor (TNF) is involved in liver damage, especially
      in fulminant hepatitis (FH). Our previous data showed that the serum level of TNF
      alpha was markedly increased in FH. To investigate the mechanism of the
      overproduction of TNF in FH patients, polymorphism of the TNF gene was studied.
      METHODS: We analyzed 120 healthy subjects (controls), 63 patients with acute
      hepatitis (AH), and 32 patients with FH. Of the 32 FH patients, 21 died or
      received liver transplantation (FH-D), and 11 survived with intensive therapy (FH
      S). The TNF-alpha promoter region at -1031, -863, -857, -308, and -238, and TNF
      beta Nco1 polymorphism sites were studied. RESULTS: (1) The four groups showed no
      differences in polymorphisms of positions -857, -308, and -238. The allelic
      frequencies of positions -1031C and -863A in the FH-D patients were significantly
      higher compared to findings in control subjects. (2) The allelic frequency of B2
      in the TNF-beta gene was significantly higher in FH patients, and particularly in
      the FH-D patients, compared to control subjects. (3) When the patients were
      divided into four groups by etiology, hepatitis A virus (HAV), HBV, HCV, and non
      A non-B non-C, the allelic frequencies of positions -863A and TNF-beta B2 in FH
      patients were increased in the non-A non-B non-C group compared to controls.
      CONCLUSIONS: FH patients with a poor prognosis had higher frequencies of
      positions -1031C and -863A in the TNF-alpha promoter region, and higher
      frequencies of the B2 allele of the TNF-beta gene. These data suggest that the
      genomic background may be associated with the prognosis of acute liver failure.

PMID- 15565406
TI  - Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune
      reactions in osteopontin transgenic mice.
AB  - BACKGROUND: Massive liver necrosis can develop as a consequence of imbalance
      between T-helper (Th)1 and Th2 immune reactions in the liver. Osteopontin is a
      glycoprotein secreted for the initiation of the Th1 immune reaction, as well as
      for extracellular matrix formation and calcium deposition in the bone and kidney.
      Osteopontin is overexpressed in Kupffer cells, macrophages, and stellate cells
      activated in injured livers. We established transgenic mice expressing
      osteopontin exclusively in hepatocytes, using a vector containing human serum
      amyloid P component promoter. The relation of Th1/Th2 immune imbalance to massive
      liver necrosis was studied using these transgenic mice. METHODS: Transgenic mice
      and C27BL/6 mice, wild-type controls of the transgenic mice, were given an
      intravenous injection of concanavalin-A, and the histological extent of liver
      injuries and plasma cytokine levels were evaluated. RESULTS: When the transgenic
      mice received concanavalin-A, massive necrosis and mononuclear cell infiltration
      developed in the liver, the extent of which was greater in the female mice than
      in the male mice. This treatment produced minimal liver injury and focal liver
      necrosis in male and female C57BL/6 mice. In these transgenic and control mice,
      plasma concentrations of interleukin (IL)-10 and interferon (IFN)-gamma were
      increased after concanavalin-A treatment. However, the upregulation of plasma IL
      10 concentration was smaller in the male and female transgenic mice than in the
      control mice, and the upregulation of the IFN-gamma concentration was greater in
      the female transgenic mice than in the female control mice. CONCLUSIONS: Th1 and
      Th2 immune reactions were deranged after concanavalin-A treatment, with Th1
      immunity predominating in transgenic mice expressing osteopontin in hepatocytes;
      this immunological imbalance may contribute to massive liver necrosis.

PMID- 15565407
TI  - An open-label study of administration of EH0202, a health-food additive, to
      patients with chronic hepatitis C.
AB  - BACKGROUND: In this study, we examined the effect of EH0202, a mixture of four
      herbal extracts that are known to induce interferons, on hepatitis C virus (HCV)
      RNA levels in patients with chronic hepatitis C. METHODS: This was an open-label
      uncontrolled study. The study subjects ingested food containing EH0202 daily for
      3 months, which was equivalent to 1 g of desiccated herbs daily. Clinical
      symptoms, hematology and biochemical examinations, urine, and HCV-RNA levels were
      examined before, during (1 month), and after the EH0202 treatment (3 months).
      RESULTS: Among the 35 patients who successfully completed the study, there were
      improvements in malaise (seen in 6 patients before and in 2 after EH0202
      treatment), bloating sensation in the abdomen (seen in 2 before and in none after
      treatment), and nausea and vomiting (seen in 2 before and in 1 after treatment).
      There were no changes in hematology or biochemical examination parameters. There
      was a statistically significant decrease in HCV-RNA levels in patients with high
      viral titers after 3 months of EH0202 administration. No serious adverse events
      were observed with the EH0202 treatment. CONCLUSIONS: These findings suggest that
      EH0202 may be safe and useful in the treatment of patients with chronic hepatitis
      C. Further studies are, however, needed to obtain a definitive conclusion.

PMID- 15565408
TI  - Severe chronic pancreatitis and severe liver cirrhosis have different frequencies
      and are independent risk factors in male Japanese alcoholics.
AB  - BACKGROUND: Chronic pancreatitis and liver cirrhosis are major alcohol-related
      diseases in most countries. Neither their specific etiologies nor the
      relationship between them is fully understood. This study was designed to examine
      a possible association between alcoholic chronic pancreatitis (ACP) and alcoholic
      liver cirrhosis (ALC), and to identify factors relating to them. METHODS: The
      subjects were 141 consenting participants from 1087 male patients consecutively
      admitted to Kurihama National Hospital from July 2000 to November 2002. All were
      negative for major medical disorders (e.g., viral hepatitis, operative history,
      malignancy), except for ACP and ALC. Analysis of each subject included background
      information (collected by face-to-face interview, regarding quantity and duration
      of drinking, usual alcoholic drinks, smoking, education, employment, and marital
      status) and signs of ACP detected on endoscopic retrograde
      cholangiopancreatography (ERCP) and ALC indicated by Child-Pugh classification.
      Subjects consenting to genome analyses ( n = 83) were genotyped for two key
      alcohol-metabolizing enzymes: alcohol dehydrogenase-2 and aldehyde dehydrogenase
      2. RESULTS: Grouping patients by ERCP grading and Child classification revealed a
      nonparallel relationship between the severities of the two diseases. This
      relationship held, even after controlling for several pertinent background
      variables (sociofamilial, drinking, clinical, and genetic factors) by logistic
      regression analysis. The drinking of spirits and a high daily consumption of
      alcohol were independent risk factors for ACP, while never-married status was the
      only risk factor identified with ALC among these male Japanese patients.
      CONCLUSIONS: Different risk factors may confer susceptibility to ACP versus ALC,
      which may explain the nonparallel relationship between the severities of the two
      diseases in Japanese alcoholics.

PMID- 15565409
TI  - Development and evaluation of FSSG: frequency scale for the symptoms of GERD.
AB  - BACKGROUND: The aim of this study was to produce a simplified questionnaire for
      evaluation of the symptoms of gastroesophageal reflux disease (GERD). METHODS: A
      total of 124 patients with an endoscopic diagnosis of GERD completed a 50-part
      questionnaire, requiring only "yes" or "no" answers, that covered various
      symptoms related to the upper gastrointestinal tract, as well as psychosomatic
      symptoms. The 12 questions to which patients most often answered "yes" were
      selected, and were assigned scores (never = 0; occasionally = 1; sometimes = 2;
      often = 3; and always = 4) to produce a frequency scale for symptoms of GERD
      (FSSG). Sensitivity, specificity, and accuracy of the FSSG questionnaire were
      evaluated in another group of patients with GERD and non-GERD. The usefulness of
      this questionnaire was evaluated in 26 other GERD patients who were treated with
      proton pump inhibitors for 8 weeks. RESULTS: When the cutoff score was set at 8
      points, the FSSG showed a sensitivity of 62%, a specificity of 59%, and an
      accuracy of 60%, whereas a cutoff score of 10 points altered these values to 55%,
      69%, and 63%. The score obtained using the questionnaire correlated well with the
      extent of endoscopic improvement in patients with mild or severe GERD.
      CONCLUSIONS: This new questionnaire is useful for the objective evaluation of
      symptoms in GERD patients.

PMID- 15565410
TI  - Dubin-Johnson-like black liver with normal bilirubin level.
AB  - Black liver is a common finding in Dubin-Johnson syndrome (DJS), which is caused
      by the lack of multidrug resistance-associated protein 2 (MRP2). Impaired
      excretion of epinephrine metabolites is believed to be a cause of black liver in
      DJS. Recently, we experienced a patient with black liver whose serum bilirubin
      level was normal. Coarse brown granules were observed in the hepatocytes, and
      this finding closely resembled that observed in DJS. However, the granules were
      negative for Schmorl staining. The MRP2 gene did not show any mutation.
      Immunostaining study demonstrated MRP2 protein expression in the liver, and it
      was localized in the canalicular membranes of hepatocytes. This case illustrates
      for the first time that DJS is not the only cause of black liver.

PMID- 15565411
TI  - Improvement of serum bilirubin levels after venesection in a patient with Dubin
      Johnson syndrome and HCV-positive chronic liver disease.
AB  - Direct-type hyperbilirubinemia in Dubin-Johnson syndrome is due to the genetic
      dysfunction of multidrug resistance protein 2. However, serum bilirubin levels
      may fluctuate as a result of acquired conditions. Iron-reduction therapy by
      venesection, an alternative to interferon, was performed in a 55-year-old male
      patient with Dubin-Johnson syndrome complicated by hepatitis C virus-positive
      chronic liver disease and hepatic iron overload. His pretreatment serum total
      bilirubin was 10.2 mg/dl, with a dominant direct fraction. The treatment induced
      a significant reduction in serum total bilirubin, although it remained as high as
      7.9 mg/dl. A negative correlation between serum total bilirubin and cumulative
      bled volume suggested that venesection could suppress bilirubin production from
      aged erythrocytes. The hepatic iron overload was distributed in hepatocyte
      lysosomes with Dubin-Johnson granules; thus, it seems that iron removal from the
      lysosomal granules may also help to reduce serum bilirubin. In conclusion, deep
      jaundice in a patient with Dubin-Johnson syndrome complicated by hepatitis C
      virus-positive chronic liver disease and iron overload was partially improved by
      iron-reduction therapy.

PMID- 15565412
TI  - Hepatic artery pseudoaneurysm associated with cholecystitis that ruptured into
      the gallbladder.
AB  - Pseudoaneurysm of the hepatic artery due to cholecystitis may be very rare, and
      in our survey of the literature, the present case report is the first case of
      such a pseudoaneurysm. A 64-year-old woman presented with upper gastrointestinal
      bleeding and severe epigastric pain. Upper gastrointestinal tract endoscopy
      revealed blood coming out of the papilla of Vater. Color-Doppler ultrasound
      imaging showed a pulsatile wave pattern in an echogenic lesion inside the
      gallbladder. Contrast-enhanced computed tomography demonstrated a 3-cm
      pseudoaneurysm in the distended gallbladder. Angiography disclosed extravasation
      originating from the right hepatic artery. Emergency selective transcatheter
      arterial embolization was performed, with intravascular stainless steel
      microcoils, and complete occlusion of the pseudoaneurysm was achieved. The
      patient underwent cholecystectomy with resection of the extrahepatic bile duct
      and biliary reconstruction in a Roux-en-Y fashion. Macroscopically, the resected
      gallbladder contained clotted blood and multiple cholesterol stones.
      Microscopically, the mucosa of the gallbladder showed extensive necrosis and many
      inflammatory cells. The final diagnosis was pseudoaneurysm of the hepatic artery
      associated with calculous gangrenous cholecystitis. Although the mechanism of the
      pseudoaneurysm remains speculative, severe inflammatory reaction in the
      gallbladder may have infiltrated the liver parenchyma and may have eroded the
      wall of the hepatic artery, thus forming a pseudoaneurysm. Hemobilia is one of
      the important differential diagnoses when unexplained gastrointestinal bleeding
      is observed, especially in patients with hepatobiliary diseases.

PMID- 15565413
TI  - Secondary resistance to imatinib mesylate in a patient with unresectable duodenal
      GIST without mutations in exons 9, 11, 13, or 17 of the c-kit protooncogene.

PMID- 15565414
TI  - A fibrolamellar carcinoma of the liver with a marked solid component.

PMID- 15565415
TI  - Resection of needle-tract implantation after percutaneous puncture for
      hepatocellular carcinoma.

PMID- 15565416
TI  - Reflux esophagitis and Helicobacter pylori: East and West.

PMID- 15565417
TI  - Hepatitis B virus genotypes in Japan--past, present, and future.

PMID- 15565418
TI  - A promising therapeutic vaccination to suppress hepatitis B virus replication in
      immunosuppressed patients.

PMID- 15565419
TI  - What factors play a crucial role in the pathogenesis of alcohol-related chronic
      pancreatitis and liver cirrhosis?

PMID- 15565420
TI  - [Why does blood have a pH-value of 7.4? The theory of acid-base management].
AB  - Aim of the present paper is to discuss the physiologic principles of the acid
      base status, in particular those of the pH value. The alpha-stat theory of acid
      base management interprets the normal value of arterial pH, usually thought of as
      being 7.40, as a value derived from the intracellular pH, which is close to
      neutrality. This appears to have offered an evolutionary advantage, since most of
      the intermediates in biosynthetic pathways are ionized at neutrality resulting in
      a decreased rate of penetration across biological membranes of these compounds
      thus producing a benefit for the economy of a cell. Finally, we present the
      clinical implications of both the alpha-stat and the pH-stat strategy of acid
      base management.

PMID- 15565421
TI  - [Diving accidents. Emergency treatment of serious diving accidents].
AB  - Decompression injuries are potentially life-threatening incidents mainly due to a
      rapid decline in ambient pressure. Decompression illness (DCI) results from the
      presence of gas bubbles in the blood and tissue. DCI may be classified as
      decompression sickness (DCS) generated from the liberation of gas bubbles
      following an oversaturation of tissues with inert gas and arterial gas embolism
      (AGE) mainly due to pulmonary barotrauma. People working under hyperbaric
      pressure, e.g. in a caisson for general construction under water, and scuba
      divers are exposed to certain risks. Diving accidents can be fatal and are often
      characterized by organ dysfunction, especially neurological deficits. They have
      become comparatively rare among professional divers and workers. However, since
      recreational scuba diving is gaining more and more popularity there is an
      increasing likelihood of severe diving accidents. Thus, emergency staff working
      close to areas with a high scuba diving activity, e.g. lakes or rivers, may be
      called more frequently to a scuba diving accident. The correct and professional
      emergency treatment on site, especially the immediate and continuous
      administration of normobaric oxygen, is decisive for the outcome of the accident
      victim. The definitive treatment includes rapid recompression with hyperbaric
      oxygen. The value of adjunctive medication, however, remains controversial.

PMID- 15565422
TI  - [Diagnosis of endolymphatic hydrops using low frequency modulated distortion
      product otoacoustic emissions].
AB  - BACKGROUND: The low frequency modulation of distortion product otoacoustic
      emissions (DPOAEs) is an objective audiometric method that appears to be a useful
      tool for the diagnosis of endolymphatic hydrops (EH), e.g. in patients with
      Meniere's disease, or in those who present only some of the symptoms of the
      disease. METHOD: Low-frequency modulated DPOAEs were registered in 20 patients
      with unilateral Meniere's disease (13 women and 7 men, aged 40-66 years) and were
      compared to a control group matched in age and gender. As a diagnostic parameter,
      the 'modulation index' MI=1/2 MS/DM was used (MS or modulation span, being the
      difference between the maximal and the minimal DPOAE-amplitude, and DM, being the
      mean of the suppressed stationary DPOAE-amplitude). RESULTS: In the patients with
      unilateral Meniere's disease, MI was lower than in the control group. This
      difference was highly significant. In 56% of the patients' contralateral ears MI
      was lower than the cut off-value and significantly lower than in the control
      group, but did not differ significantly from the patients' ipsilateral ears.
      CONCLUSION: The registration of low-frequency modulated DPOAEs is comparable to
      the generally applied transtympanic electrocochleography in its diagnostic
      validity. The method is fast and non-invasive and could be applied to monitor the
      course of the disease.

PMID- 15565423
TI  - [Two-tier screening process (TEOAE/AABR) reduces recall rates in newborn hearing
      screening].
AB  - BACKGROUND: 1-2/1,000 newborns are affected by connatal permanent hearing
      impairment. Clinical diagnosis is often delayed. This demands newborn hearing
      screening (NHS). Some questions regarding the optimal method remain unsolved.
      METHODS: The newborns in the obstetrical department (low-risk group) are tested
      by automated transitory evoked otoacustic emissions (TEOAE). TEOAE-fail is
      followed by automated auditory brainstem response (AABR) examination. All sick
      newborns admitted to the pediatric department (high-risk group) are primarily
      tested using AABR. Pathological AABR-testing leads to pedaudiological diagnostic
      work-up. RESULTS: In the low-risk group, 82 out of 1,584 newborns failed TEOAE
      testing (recall 5.18%). Only 5 of these patients failed consecutive AABR
      examination (recall 0.32%). Permanent hearing loss was finally confirmed in 3
      children (0.13%). 10 out of 755 newborns in the high-risk group failed AABR
      testing (1.32%). In 6 of these children, hearing loss was confirmed (0.79%).
      CONCLUSION: A two-tier screening process as described is able to reduce recall
      rate, overall expenses and parental anxiety.

PMID- 15565424
TI  - [Neurofeedback-based EEG alpha and EEG beta training. Effectiveness in patients
      with chronically decompensated tinnitus].
AB  - BACKGROUND: Persisting tinnitus is an often devastating disease condition with
      restricted and rarely successful therapeutic options. PATIENTS AND METHODS: The
      present study investigates the therapeutic effect of short term neurofeedback
      based EEG-Alpha- and EEG-Beta-training in 40 patients suffering from "chronic
      decompensated tinnitus". Patients were assigned to the Alpha or Beta group
      according to results of an initial EEG monitored stress-test. Four patients were
      excluded because they showed abnormal reactions in both EEG patterns. RESULTS:
      During 12 sessions, 23 patients succeeded to increase EEG Alpha activity by 16%
      (p< or =0.042) while 13 patients achieved no decrease of EEG Beta activity.
      However, both groups showed a significant reduction of subjective tinnitus
      annoyance by the end of the therapy (p< or =0.001) CONCLUSIONS: The results
      indicate that neurofeedback may represent a new promising technique in the
      therapy of chronic decompensated tinnitus. However, it remains to be established
      whether the reduction of tinnitus annoyance results from the altered brain
      activity patterns supported by the neurofeedback learning process.

PMID- 15565425
TI  - [Shock trauma room management of the multiple-traumatized patient with skull
      brain injuries. A systematic review of the literature].
AB  - This overview reviews the literature on multiply injured patients with traumatic
      brain injuries. Clinical trials were systematically collected (MEDLINE, Cochrane,
      and hand searches) and classified into evidence levels (1 to 5 according to the
      Oxford system).A detailed analysis of the literature of traumatic brain injuries
      has been elaborated by the Brain Trauma Foundation and has been published in the
      World Wide Web (http://www2.braintrauma.org/). The following procedures should be
      performed in the emergency room for multiply injured patients with traumatic
      brain injuries: (1) recording of precise history to identify risk factors for
      severe traumatic brain injury, (2) measurement of the Glasgow Coma Scale (GCS),
      pupillary reflex, and mean arterial pressure, (3) diagnostic evaluation with a CT
      scan, and (4) rapid surgical decompression if indicated.

PMID- 15565426
TI  - Development of a standard set of microsatellite reference alleles for
      identification of grape cultivars.
AB  - In order to investigate the comparability of microsatellite profiles obtained in
      different laboratories, ten partners in seven countries analyzed 46 grape
      cultivars at six loci (VVMD5, VVMD7, VVMD27, VVS2, VrZAG62, and VrZAG79). No
      effort was made to standardize equipment or protocols. Although some partners
      obtained very similar results, in other cases different absolute allele sizes
      and, sometimes, different relative allele sizes were obtained. A strategy for
      data comparison by means of reference to the alleles detected in well-known
      cultivars was proposed. For each marker, each allele was designated by a code
      based on the name of the reference cultivar carrying that allele. Thirty-three
      cultivars, representing from 13 to 23 alleles per marker, were chosen as
      references. After the raw data obtained by the different partners were coded,
      more than 97% of the data were in agreement. Minor discrepancies were attributed
      to errors, suboptimal amplification and visualization, and misscoring of
      heterozygous versus homozygous allele pairs. We have shown that coded
      microsatellite data produced in different laboratories with different protocols
      and conditions can be compared, and that it is suitable for the identification
      and SSR allele characterization of cultivars. It is proposed that the six markers
      employed here, already widely used, be adopted as a minimal standard marker set
      for future grapevine cultivar analyses, and that additional cultivars be
      characterized by means of the coded reference alleles presented here. The
      complete database is available at http://www.genres.de/eccdb/vitis/ Cuttings of
      the 33 reference cultivars are available on request from the Institut National de
      la Recherche Agronomique Vassal collection (didier.vares@ensam.inra.fr).

PMID- 15565427
TI  - Improvements in an in-vitro assay for excitotoxicity by measurement of early gene
      (c-fos mRNA) levels.
AB  - Quantitative, real-time reverse transcription-polymerase chain reaction (RT-PCR)
      measurements were made to investigate the levels of c-fos mRNA as one measure of
      the expression of the c-fos gene. Exposure of mouse cerebellar granule cells to
      excitotoxic concentrations of glutamate (Glu) and aspartate (Asp) led to a
      changed time profile for mRNA expression, from a transient c-fos expression at 15
      30 min to a delayed, elevated and sustained expression at later time points which
      was prevented by selective antagonism of the NMDA receptor but not of the
      AMPA/kainate receptor demonstrating that this c-fos induction was mediated
      through the specific activation of the NMDA Glu receptor subtype. The question as
      to whether c-fos expression changes could be used to predict excitotoxicity was
      addressed by testing the c-fos response of the cultures to several compounds, at
      low (and therefore non-toxic) and high (toxic) concentrations at two suitable
      time-points of exposure (30 and 240 min), in the presence and absence of Glu
      receptor antagonists. The compounds were divided into four groups, excitotoxins,
      neurotoxic but non-excitotoxic compounds, neuroactive but non-toxic compounds,
      and compounds that were toxic to other target organelles. The results of this
      study, using real-time RT-PCR, support the proposal that c-fos mRNA can be used
      as a specific biomarker of excitotoxicity and moreover encourage further studies
      to employ this highly sensitive, quantifiable and reproducible technique in a
      high throughput screen, with minimal use of animals for primary culture set-up.
      Furthermore, this test has the potential for application in screening newly
      designed excitatory amino acid receptor antagonists in the search for clinically
      relevant drugs to treat a variety of neuropathologies.

PMID- 15565428
TI  - Elevated internal exposure of children in simulated acute inhalation of volatile
      organic compounds: effects of concentration and duration.
AB  - When deriving health-based exposure limits in recent years, increasing attention
      has been drawn to susceptible subpopulations, in particular to children. We
      investigated the differences in kinetics between children and adults during
      inhalation of styrene as a typical category-3 volatile organic compound (VOC),
      i.e., a gas with a low reactivity and low water solubility allowing a high rate
      of alveolar absorption. Internal exposure was simulated using a physiologically
      based kinetic model over a broad range of airborne concentrations (1-1000 ppm)
      and for an exposure time of up to 8 h according to the scenario in the acute
      exposure guideline level (AEGL) program. Age-specific anatomical and
      physiological parameters and compound-specific data was derived from the
      literature. The calculated concentrations in arterial blood are higher in
      children than in adults, and are highest in the newborn. For an 8-h exposure to
      low concentrations, the calculated arterial concentration in the newborn is
      higher by a factor of 2.3 than in the adult. This is due mainly to the relatively
      high ventilation rate and the immature metabolism. With increasing airborne
      concentration, the ratio of arterial concentrations (newborn/adult) increases to
      a maximum of 3.8 at 130 ppm in ambient air, and declines with further increments
      of concentration to a value of 1.7. This is because the metabolism of the newborn
      becomes non-linear at lower concentrations than in adults. At high
      concentrations, metabolism is saturated in both age groups. For shorter
      exposures, the dose dependency of the concentration ratios (newborn/adult) is
      less pronounced. This is the first article to show that the intraspecies
      assessment factor may vary with concentration and duration of exposure.

PMID- 15565429
TI  - Acute diclofenac treatment attenuates lipopolysaccharide-induced alterations to
      basic reward behavior and HPA axis activation in rats.
AB  - RATIONALE: Non-steroidal anti-inflammatory drugs (NSAIDs) counteract stress
      hormone and pro-inflammatory cytokine activation, and are being considered as
      therapeutics for Alzheimer's and Parkinson's disease, and multiple sclerosis.
      Previous data from our laboratory revealed that repeated treatment with the NSAID
      diclofenac attenuated lipopolysaccharide (LPS)-induced alterations to reward
      behavior, implicating a role for NSAIDs in alleviating depressive-like behavior.
      OBJECTIVES: To extend these findings, we sought to determine whether acute
      treatment with diclofenac would attenuate LPS-induced alterations to basic reward
      behavior, as well as neuroendocrine and neuroimmune function. METHODS: Male,
      Wistar rats (n=8-9/grp) pressed a lever for sucrose pellet reward and after
      establishing a steady baseline were exposed to an injection of saline (1 ml/kg,
      SC) or diclofenac (2.5 mg/kg, SC) 30 min prior to a second injection of saline or
      LPS (20 microg/kg, IP). RESULTS: In saline pre-treated rats, LPS significantly
      reduced rate of sucrose pellet self-administration and total reinforcers
      obtained, suggestive of an anhedonia response. In addition, LPS increased
      corticosterone release, increased plasma intereleukin (IL)-1beta release,
      increased IL-1beta and IL-6 mRNA in hippocampus, increased corticotropin
      releasing hormone (CRH) mRNA in pituitary, and decreased CRH-1 mRNA in pituitary.
      Importantly, the behavioral and neuroendocrine effects, but not neuroimmune
      effects, produced by LPS were significantly attenuated in rats pre-treated with
      diclofenac. CONCLUSIONS: These new data provide a comprehensive assessment of the
      acute effects of diclofenac on LPS exposure in rats and confirm a role for NSAIDs
      in attenuating endotoxin-induced anhedonia. Of particular importance, the data
      reveal that the observed effects are mediated via the hypothalamic pituitary
      adrenal axis at the level of the pituitary or above.

PMID- 15565430
TI  - Quantitative analysis of the effects of some "atypical" and "conventional"
      antipsychotics on progressive ratio schedule performance.
AB  - RATIONALE: Performance on progressive ratio schedules has been proposed as a
      means of assessing the effects of drugs on the value or "efficacy" of
      reinforcers. A mathematical model affords a basis for quantifying the effects of
      drugs on progressive ratio schedule performance. According to this model, the
      relation between response rate and ratio size is described by a bitonic (inverted
      U) function. One parameter of the function, alpha, expresses the motivational or
      "activating" effect of the reinforcer (duration of activation of responding
      produced by the reinforcer), whereas another parameter, delta, expresses the
      minimum time needed to execute a response, and is regarded as an index of "motor
      capacity". In a previous experiment we found that the "atypical" antipsychotic
      clozapine increased alpha, indicating an increase in the efficacy of a food
      reinforcer. OBJECTIVE: We examined the effects of four "atypical" and four
      "conventional" antipsychotics on progressive ratio schedule performance. METHODS:
      Rats responded for a sucrose reinforcer (0.6 M, 50 microl) on a time-constrained
      progressive ratio schedule (50-min sessions). After 90 preliminary training
      sessions, they received acute doses of antipsychotics (doses in mg kg(-1)):
      atypical: clozapine (2, 4, 8, IP; n=15), quetiapine (1.25, 2.5, 5, 10, SC; n=23),
      olanzapine (0.25, 0.5, 1, IP; n=15), ziprasidone (0.625, 1.25, 2.5, IP, n=15);
      conventional: haloperidol (0.025, 0.05, 0.1, IP, n=15), pimozide (0.125, 0.25,
      0.5, IP; n=15), raclopride (0.25, 0.5, 1, SC; n=12), cis-flupenthixol (0.2, 0.4,
      0.8, SC; n=15). Values of a and delta were estimated from the response rate
      functions obtained under each treatment condition, and were compared between drug
      and vehicle-alone treatments. RESULTS: The atypical antipsychotics significantly
      increased alpha (indicating enhancement of reinforcer efficacy), and also
      increased delta (indicating reduction of motor capacity). Haloperidol, pimozide
      and raclopride significantly increased delta; none of the conventional
      antipsychotics significantly altered alpha. CONCLUSIONS: The results extend
      previous findings with clozapine to other atypical antipsychotics and suggest
      that enhancement of the efficacy of reinforcers may be a common feature of
      atypical antipsychotics not shared by conventional antipsychotics.

PMID- 15565431
TI  - Natural reward-related learning in rats with neonatal ventral hippocampal lesions
      and prior cocaine exposure.
AB  - RATIONALE: Psychostimulant injections in rats have been shown to alter future
      performance in natural reward conditioning. These effects may represent a
      persistent impact of drugs on neurocircuits that interface cognitive and
      motivational processes, which may be further altered in neuropsychiatric
      conditions that entail increased addiction vulnerability. OBJECTIVE: This study
      investigated whether a rat model of schizophrenia with cocaine addiction
      vulnerability shows altered natural reward conditioning with or without prior
      cocaine exposure. METHODS: Adult rats with SHAM or neonatal ventral hippocampal
      lesions were given cocaine (15 mg/kg per day for 5 days) or saline injections,
      followed 7 days later by natural reward-conditioned learning. Over ten daily
      sessions, water-restricted rats were assessed for durations of head entries into
      a magazine during random water presentations, a conditioning stimulus phase
      predictive of the water reward, and an "inappropriate" phase when conditioning
      stimuli were absent and reward presentation would be delayed. RESULTS: Over
      repeated sessions, lesioned and SHAM rats showed similar reductions in total
      magazine entry durations, with similar increases in the allocations of entry
      times during the water presentation. However, lesioned rats, especially those
      exposed to cocaine, demonstrated reduced allocations of magazine entry times
      during the conditioning stimulus phase, and increased allocations during the
      inappropriate phase. CONCLUSIONS: Intact natural reward motivation accompanied by
      deficient learning of complex contingencies to guide efficient reward approach
      may represent a form of impulsivity as an addiction vulnerability trait marker in
      an animal model of schizophrenia.

PMID- 15565432
TI  - Plasma levels of leptin and endogenous immune modulators during treatment with
      carbamazepine or lithium.
AB  - Several psychopharmacological agents induce weight gain. Recent studies have
      suggested that the tumor necrosis factor-alpha (TNF-alpha) cytokine system is
      pathophysiologically involved. To assess whether carbamazepine and lithium, which
      have been reported to lead to weight gain, have effects on the circulating levels
      of cytokines, we measured plasma levels of TNF-alpha, its soluble receptors sTNF
      R p55 and p75, and leptin, as well as weight in 25 inpatients receiving lithium
      (n=10) or carbamazepine (n=15) weekly during the first 4 weeks of treatment. We
      found an increase in the body mass index and in TNF-alpha and its soluble
      receptor levels, but not in leptin levels over the 4 weeks of treatment. These
      changes did not differ between treatment groups. Changes of weight during the
      first week of treatment, but no other parameter, strongly predicted weight change
      until endpoint. We conclude that the mood stabilizers carbamazepine and lithium
      have similar effects on the TNF-alpha system and do not affect leptin levels.

PMID- 15565433
TI  - Calorie restriction increases cigarette use in adult smokers.
AB  - RATIONALE: Cigarette smokers weigh less than nonsmokers, and smokers often gain
      weight when they quit. This is a major barrier to smoking cessation, especially
      among women. However, strict dieting is not recommended during smoking cessation
      out of concern that it might promote relapse. This concern derives, in part, from
      the observation that calorie restriction increases self-administration of drugs
      of abuse in animals. This relationship has never been experimentally demonstrated
      in humans. OBJECTIVES: To evaluate whether calorie restriction increases
      cigarette smoking in humans. METHODS: Seventeen (nine males, eight females)
      healthy, normal-weight smokers not attempting to quit were cycled in partially
      counterbalanced order, double-blind, through four diets-normal calorie (2,000
      2,800 kcal/day), low calorie (700 kcal/day deficit), low-carbohydrate
      (CHO)/normal-calorie, and low-CHO/low-calorie-for 6 days per diet in an inpatient
      research ward. Smoking was assessed by cigarette counts, breath carbon monoxide
      (CO) levels, and cigarette craving. RESULTS: Compared with the normal-calorie
      diet, while on the low-calorie diet, subjects smoked 8% more cigarettes (P<0.02)
      and had 11% higher breath CO levels (P<0.01). The low-CHO/normal-calorie diet
      showed no significant effect on either variable, but there was a 15% increase in
      breath CO levels (P<0.05) on the low-CHO/low-calorie diet. There were no changes
      in self-reported cigarette craving or mood. CONCLUSIONS: Consistent with animal
      studies, moderate calorie restriction was associated with a small but
      statistically significant increase in cigarette smoking, with no independent
      effect of CHO deprivation. These findings suggest that dieting may increase
      smoking behavior and could impede smoking-cessation attempts.

PMID- 15565434
TI  - Attenuation of nicotine's discriminative stimulus effects in rats and its
      locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists.
AB  - RATIONALE: Reports have indicated that administration of nicotine inhibits, while
      withdrawal of chronically administered nicotine augments effects of serotonergic
      5HT2A/2C agonists. OBJECTIVE: It was our objective to determine whether 5HT2A/2C
      agonists can modulate the discriminative stimulus effects of nicotine in rats or
      its locomotor activity effects in mice. METHODS: Adult male Sprague-Dawley rats
      were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever,
      fixed-ratio (FR10), food-reinforced, operant-conditioning task during daily
      (Monday-Friday) 15-min experimental sessions. After characterizing a dose
      response curve for nicotine, we tested the ability of the 5HT(2A/2C) agonists (+/
      )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCL (DOI; 0.18-1.0 mg/kg) and 1
      (4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 0.1-1.0 mg/kg), the 5HT2C
      agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212; 0.1 mg/kg-1.0
      mg/kg), and the 5HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin
      hydrobromide (8-OH-DPAT; 0.01 mg/kg-1.0 mg/kg) to modulate nicotine's
      discriminative stimulus effects. After finding that DOI was able to attenuate the
      percentage nicotine lever responding (%NLR), we tested for it to also reverse
      nicotine's effects on locomotor activity in mice. RESULTS: The 5HT2A/2C agonists
      in particular DOI-dose dependently attenuated %NLR. The effects of DOI were
      reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had
      irregular effects among rats and only reduced %NLR to below 50% levels at doses
      markedly suppressing responding. DOI also dose dependently blocked nicotine's
      acute rate-lowering locomotor activity effects. CONCLUSIONS: These results
      indicate that activation of serotonin 5HT2A/2C receptors can blunt the
      discriminative stimulus and locomotor activity effects of nicotine and presents
      the possibility that activation of these receptors might also be able to
      attenuate other effects of nicotine.

PMID- 15565435
TI  - Excitability of the motor cortical representation of the external anal sphincter.
AB  - This study was designed to assess the excitability of the motor cortical
      representation of the external anal sphincter by using transcranial magnetic
      stimulation (TMS). In six healthy volunteers, the rest motor threshold and the
      duration of the cortical silent period were determined with single TMS pulses,
      and the intracortical inhibition and facilitation were measured with paired TMS
      pulses. Values obtained from the anal sphincter were compared with those obtained
      from a muscle in the right hand. All subjects completed the study. Rest motor
      threshold and intracortical facilitation were similar in both muscles. In
      contrast, cortical silent period duration and intra-cortical inhibition were less
      for the anal sphincter than for hand muscle. This study has opened new
      perspectives for the investigation of anal sphincter cortical control in humans.

PMID- 15565436
TI  - Components of sensorimotor adaptation in young and elderly subjects.
AB  - Previous studies have found that sensorimotor adaptation to visual distortions is
      degraded in seniors compared with younger subjects, whereas after-effects on
      removal of the distortion are age-independent. The latter finding was interpreted
      as evidence that adaptive recalibration is not affected by old age, and that the
      observed degradation is therefore due to impairment of strategic control.
      However, after-effects are not a reliable measure of recalibration, because they
      can be artificially inflated by perseveration, a characteristic symptom in old
      age. The present work therefore introduces a test of recalibration which is
      insensitive to perseveration. Twelve young and twelve old subjects executed
      center-out pointing movements while visual feedback about their fingertip was
      either veridical (baseline), 60-deg rotated (adaptation), or absent (after
      effect). They also executed tracking movements toward an unpredictably moving
      object before and after the pointing task. Seniors adapted less than younger
      subjects but their after-effects were not degraded. More importantly, transfer of
      adaptation from a pointing to a tracking task was not degraded in seniors. The
      latter outcome documents, in a more compelling fashion than previous work, that
      recalibration in the elderly is not impaired, and that the observed deficit of
      adaptation is therefore most probably because of impaired strategic control. This
      conclusion is supported by two additional findings: compared with young subjects
      our seniors performed less well on a cognitive screening test and acquired no
      explicit knowledge about the nature of the imposed visual distortion.

PMID- 15565437
TI  - Uric acid stones following hepatic transplantation.
AB  - We report the case of a 52 year old man with a history of insulin-requiring
      diabetes and hepatitis B with cirrhosis who received an orthotopic liver
      transplant. One year later he developed renal colic and was found to have a 3 mm
      stone at the left ureterovesical junction. Numerous other stones formed and
      infrared spectroscopy analysis demonstrated all to be composed of 100% uric acid.
      Urine collections demonstrated a low urine pH of 5.1 without hyperuricosuria. His
      stones were effectively prevented with potassium citrate therapy. Few incidence
      data are available for uric acid stone occurrence in solid organ recipients.
      Calcineurin inhibitors are thought to often cause hyperuricemia on the basis of
      decreased urate excretion. However, this effect would not be expected to cause
      hyperuricosuria nor uric acid stones. This class of drugs may also be associated
      with low urine pH, perhaps on the basis of hypoaldosteronism, but the
      contribution of such a syndrome to uric acid stone formation is not established.

PMID- 15565439
TI  - Renal tubular cell damage and oxidative stress in renal stone patients and the
      effect of potassium citrate treatment.
AB  - Our objective was to evaluate the oxidative stress and renal tubular cell damage
      in patients who have renal stones compared to normal subjects. The patients were
      re-evaluated after 1-months supplementation with potassium citrate. We recruited
      30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled
      for surgical stone removal the following month, and 30 healthy non-stone formers
      (14 males and 16 females). Two 24-h urine samples and one heparinized blood
      sample were collected from each subject. Plasma was separated from the
      erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium,
      phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein
      thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were
      analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione
      peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium,
      sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total
      protein (U-protein) and N-acetyl-beta-glucosaminidase (NAG) activity. For the
      stone patients, urine and blood samples were re-evaluated after supplementation
      with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher
      plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium,
      phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U
      MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and
      vitamin E, when compared with controls. After potassium citrate supplementation,
      P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and
      citrate increased. Renal stone disease is associated with high oxidative stress
      and damage to renal tubular cells. These abnormalities are coincident with an
      increase in blood lipid peroxidation products and a decrease in antioxidant
      status. Although supplementation with potassium citrate improved urinary citrate
      levels and oxidative stress, it neither reduced urinary lipid peroxidation
      products nor remedied the damage to renal tubular cells, probably due to the
      existence of kidney stones.

PMID- 15565440
TI  - Intercellular calcium signalling in cultured renal epithelia: a theoretical study
      of synchronization mode and pacemaker activity.
AB  - We investigate a two-dimensional lattice model representation of intercellular
      Ca2+ signalling in a population of epithelial cells coupled by gap junctions. The
      model is based on and compared with Ca2+ imaging data from globally bradykinin
      stimulated MDCK-I (Madin-Darby canine kidney)-I cell layers. We study large-scale
      synchronization of relevance to our laboratory experiments. The system is found
      to express a wealth of dynamics, including quasiperiodic, chaotic and multiply
      periodic behaviour for intermediate couplings. We take a particular interest in
      understanding the role of "pacemaker cells" in the synchronization process. It
      has been hypothesized that a few highly hormone-sensitive cells control the
      collective frequency of oscillation, which is close to the natural frequencies
      (without coupling) of these cells. The model behaviour is consistent with the
      conjectures of the pacemaker cell hypothesis near the critical coupling where the
      cells lock onto a single frequency. However, the simulations predict that the
      frequency in globally connected systems decreases with increasing coupling. It is
      found that a pacemaker is not defined by its natural frequency alone, but that
      other intrinsic or local factors must be considered. Inclusion of partly
      sensitized cells that do not oscillate autonomously in the cell layer increases
      the coupling necessary for global synchronization. For not excessively high
      coupling, these cells oscillate irregularly and with distinctive lower
      frequencies. In summary, the present study shows that the frequency of
      synchronized oscillations is not dictated by one or few fast-responding cells.
      The collective frequency is the result of a two-way communication between the
      phase-advanced pacemaker and its environment.

PMID- 15565438
TI  - Intestinal transport of an obdurate anion: oxalate.
AB  - In this review, we focus on the role of gastrointestinal transport of oxalate
      primarily from a contemporary physiological standpoint with an emphasis on those
      aspects that we believe may be most important in efforts to mitigate the untoward
      effects of oxalate. Included in this review is a general discussion of intestinal
      solute transport as it relates to oxalate, considering cellular and paracellular
      avenues, the transport mechanisms, and the molecular identities of oxalate
      transporters. In addition, we review the role of the intestine in oxalate disease
      states and various factors affecting oxalate absorption.

PMID- 15565441
TI  - Anion interactions with Na,K-ATPase: simultaneous binding of nitrate and eosin.
AB  - Nucleotide binding affinity to Na,K-ATPase is reduced by a number of anions such
      as nitrate and perchlorate in comparison with affinity in the presence of
      chloride (all with sodium as the cation). The reduction correlates with the
      position of these anions in the Hofmeister series. Transient kinetic experiments
      using the fluorescent dye eosin-which binds to the nucleotide site of the Na,K
      ATPase-show that simultaneous anion binding, exemplified with nitrate, and eosin
      binding is possible. The effect of nitrate on eosin binding is reflected in a
      decreased binding-rate constant and an increased dissociation rate constant,
      leading to a decreased equilibrium binding constant for eosin. Since eosin
      binding is analogous with nucleotide binding to Na,K-ATPase, the results suggest
      the simultaneous presence of nucleotide and anion binding sites.

PMID- 15565442
TI  - Mitochondria optical parameters are dependent on their energy state: a new
      electrooptical effect?
AB  - The membrane potential of mitochondria determines, to a large extent, their
      functional state and the response to the changing conditions of the environment.
      A correlation was found between the changes in the optical characteristics of
      isolated mitochondria and the composition of the incubation medium, which
      determines the potential of the inner mitochondrial membrane. The measurements
      performed by the method of coherent phase microscopy made it possible to
      establish a linear dependence of the phase height on the value of the membrane
      potential and to calculate the electrooptical constant, K approximately equal to
      (3-4) x 10(-7) m/V.

PMID- 15565443
TI  - Cytotoxic activity of a new paclitaxel formulation, Pacliex, in vitro and in
      vivo.
AB  - BACKGROUND: The paclitaxel formulation, Taxol (Bristol-Myers Squibb), is one of
      the most effective anticancer agents used today. However; it is associated with
      serious side effects believed to be caused by the Cremophor EL used for its
      formulation. AIM: To evaluate the cytotoxic activity of a new paclitaxel
      formulation, Pacliex (developed by Oasmia Pharmaceutical, Uppsala, Sweden), a
      mixed micelles preparation in which an amphiphilic synthetic derivative of
      retinoic acid replaced Cremophor EL/ethanol vehicle. METHOD: In this study, three
      model systems were used to evaluate the cytotoxic activity of Pacliex and other
      paclitaxel preparations. The cytotoxic activities of Pacliex, Taxol and
      paclitaxel in ethanol were investigated against a panel of ten human tumor cell
      lines using the fluorometric microculture cytotoxicity assay (FMCA). Low- and
      high- proliferating in vitro hollow fiber model of two cell lines, the leukemia
      CCRF-CEM and the myeloma RPMI 8226/S cell lines, were used to assess the
      cytotoxic activity of the three formulations. The in vivo hollow fiber model of
      the two cell lines was used for assessment of Pacliex and Taxol activity. The [3
      4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was
      utilized to analyze the in vitro and in vivo hollow fiber data. RESULT: Pacliex
      was somewhat more effective than Taxol in the more sensitive cell lines. The
      activity of Taxol was more pronounced in the resistant cell lines due to an
      additive effect of the vehicle used. The three formulations showed similar
      activity in both the low- and high-proliferating in vitro hollow fiber cultures.
      The in vivo hollow fiber cytotoxic activity of Pacliex was similar to that of
      Taxol. Putting all the results together, it was found that all the three
      formulations had similar in vitro and in vivo activity. CONCLUSION: The three in
      vitro and in vivo models confirmed the similarity of the cytotoxic activities of
      Pacliex and Taxol. Considering the above, Pacliex could be an interesting
      alternative Cremophor EL-free formulation of paclitaxel.

PMID- 15565444
TI  - A phase I and pharmacologic study of the MDR converter GF120918 in combination
      with doxorubicin in patients with advanced solid tumors.
AB  - BACKGROUND: Resistance to chemotherapy can partly be explained by the activity of
      membrane bound P-glycoprotein. Competitive inhibition of P-glycoprotein, by
      multidrug resistance (MDR) converters, may overcome this MDR. Previously studied
      MDR converters either have serious intrinsic side effects or considerably
      influence the pharmacokinetics of cytotoxic agents at concentrations
      theoretically required to convert MDR. GF120918 is a third-generation MDR
      converter with high affinity for P-glycoprotein and can be given orally. We
      performed a phase 1 study with escalating doses of GF120918 in combination with
      doxorubicin. PATIENTS AND METHODS: The study group comprised 46 patients with
      advanced solid tumors. Doxorubicin was administered on day 1 (cycle 1), GF120918
      on days 22-24 (cycle 2), and on days 29-33 with doxorubicin administered on day
      31 (cycle 3). Pharmacokinetics of both GF120918 and doxorubicin were studied. The
      starting daily dose of GF120918 was 50 mg and was to be increased in subsequent
      cohorts until a steady state plasma level of 100 ng/ml was reached. The starting
      dose of doxorubicin was 50 mg/m2 and was to be increased after reaching the
      target dose level of GF120918. RESULTS: In 37 of the 46 patients, full
      pharmacokinetic data from the three scheduled cycles were obtained.
      Pharmacokinetics of GF120918 showed a less than linear increase in Cmax with
      increasing doses, with considerable interpatient variation. The target steady
      state plasma level for GF120918 was exceeded in 12 out of 19 patients who
      received 400 mg GF120918 alone twice daily and in 12 of 17 patients who received
      400 mg GF120918 twice daily in combination with doxorubicin. GF120918
      pharmacokinetics were not influenced by coadministration of doxorubicin. The
      doxorubicin AUC was only marginally influenced by GF120918 and only at the
      highest dose levels. In these patients there was a significant increase in the
      AUC of doxorubicinol in cycle 3 as compared to cycle 1. Hematologic toxicity
      mainly consisted of neutropenia and was more severe in cycle 3 than in cycle 1
      (13 vs 5 patients with grade 4 neutropenia, P=0.003). Neutropenic fever was the
      dose-limiting toxicity at a doxorubicin dose of 75 mg/m2 with 400 mg GF120918
      twice daily. The toxicity of GF120918 was limited to somnolence in eight patients
      and occasional gastrointestinal complaints. CONCLUSION: GF120918 is an MDR
      converter with only minimal side effects at a dose level yielding concentrations
      able to convert the action of P-glycoprotein in vitro. A doxorubicin dose of 60
      mg/m2 on day 3 in combination with 400 mg GF120918 twice daily on days 1-5 is an
      acceptable regimen for further clinical trials.

PMID- 15565445
TI  - Residual stress generation and necrosis formation in multi-cell tumour spheroids.
AB  - We consider how cell proliferation and death generate residual stresses within a
      multi-cell tumour spheroid (MCTS). Previous work by Jones and co-workers [8] has
      shown that isotropic growth in a purely elastic MCTS produces growth induced
      stresses which eventually become unbounded, and hence are physically unrealistic.
      Since viscoelastic materials show stress relaxation under a fixed deformation we
      consider the effect of the addition of a small amount of viscosity to the elastic
      system by examining formation of equilibrium stress profiles within a Maxwell
      type viscoelastic MCTS. A model of necrosis formation based upon that proposed by
      Please and co-workers (see [16] [17] [18]) is then presented in which necrosis
      forms under conditions of adverse mechanical stress rather than in regions of
      extreme chemical stress as is usually assumed. The influence of rheology on
      necrosis formation is then investigated, and it is shown that the excessive
      stress generated in the purely elastic tumour can be relieved either by the
      addition of some viscosity to the system or by accounting for an inner necrotic
      interface with an appropriate stress boundary condition.

PMID- 15565446
TI  - A branching model for the spread of infectious animal diseases in varying
      environments.
AB  - This paper is concerned with a stochastic model, describing outbreaks of
      infectious diseases that have potentially great animal or human health
      consequences, and which can result in such severe economic losses that immediate
      sets of measures need to be taken to curb the spread. During an outbreak of such
      a disease, the environment that the infectious agent experiences is therefore
      changing due to the subsequent control measures taken. In our model, we introduce
      a general branching process in a changing (but not random) environment. With this
      branching process, we estimate the probability of extinction and the expected
      number of infected individuals for different control measures. We also use this
      branching process to calculate the generating function of the number of infected
      individuals at any given moment. The model and methods are designed using
      important infections of farmed animals, such as classical swine fever, foot-and
      mouth disease and avian influenza as motivating examples, but have a wider
      application, for example to emerging human infections that lead to strict
      quarantine of cases and suspected cases (e.g. SARS) and contact and movement
      restrictions.

PMID- 15565447
TI  - Phase locking in integrate-and-fire models with refractory periods and
      modulation.
AB  - It is known [8, 11, 16, 26] that phase locking can entrain frequency information
      when the leaky integrate-and-fire (IF) model of a neuron is forced by a periodic
      function. We show that this is still the case when the IF model is made more
      biologically realistic. We incorporate into our model spike dependent threshold
      modulation and refractory periods. Consecutive firing times from this model and
      their respective interspike intervals are related by an annulus map. We prove a
      general theorem concerning orientation reversing annulus twist homeomorphisms,
      which shows that our map admits a unique rotation number. This implies, in
      particular, that chaotic behaviour is not possible in our model and phase locking
      is predicted.

PMID- 15565448
TI  - Successful treatment of pure red cell aplasia associated with systemic lupus
      erythematosus with oral danazol and steroid.
AB  - We describe a middle-aged Chinese systemic lupus erythematosus (SLE) patient
      developing steroid refractory and transfusion dependent red cell aplasia. Oral
      danazol 200 mg twice per day was started together with low-dose prednisolone
      therapy. There was no further recurrence of anemia 1 month after this combined
      therapy.

PMID- 15565449
TI  - Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein
      activity and nitrite levels in high fructose-fed rats.
AB  - Chronic feeding of fructose to normal rats causes impaired glucose tolerance,
      loss of tissue sensitivity to insulin, hyperinsulinemia and hypertension. alpha
      Lipoic acid (LA), a co-enzyme known for its potent antioxidant effects,
      stimulates insulin-mediated glucose uptake in clinical and experimental diabetes.
      The purpose of this study was to examine whether LA can mitigate fructose-induced
      insulin resistance and associated abnormalities. Male Wistar rats of body weights
      150-170 g were divided into 4 groups containing 12 rats each. Control rats
      received a control diet containing starch and water ad libitum. Fructose rats
      received a fructose-enriched diet (>60% of total calories). Fructose + LA rats
      received a fructose diet and LA (35 mg/kg b.w.) intraperitoneally. Control + LA
      rats received a normal diet and LA (35 mg/kg b.w.) intraperitoneally. After the
      treatment period of 20 days, blood pressure (BP) was measured. Oral glucose
      tolerance test, insulin-sensitivity index, urea and creatinine clearance tests,
      and plasma and urinary sodium and potassium levels were analysed. Kallikrein
      activity and nitrite content were assayed. Additionally, the activities of RBC
      membrane Na(+)/K(+) ATPase and Ca(2+) ATPase enzymes were assayed. Fructose rats
      showed increased BP, decreased glucose tolerance, decreased insulin sensitivity
      and altered sodium and potassium levels and renal clearance. LA supplementation
      mitigated these alterations. The increase in BP was attenuated and the levels of
      biochemical parameters were brought close to normal. The BP-lowering effect of LA
      in fructose rats may be related to improvement in insulin sensitivity.

PMID- 15565450
TI  - Choroid plexus adenoma: case report and review of the literature.
AB  - CASE REPORT: An 8-month-old infant with macrocephaly was found to have
      hydrocephalus and a cystic third ventricular tumour; biopsy of the tumour showed
      a choroid plexus adenoma. The tumour was attached to the ependymal lining and was
      strongly adherent to the walls and floor of the anterior third ventricle.
      TREATMENT: After biopsy, it was felt that a radical resection would carry a high
      risk of injury to the floor of the third ventricle and cause new neurological
      deficits. Therefore, an external ventricular drain was inserted and bilateral
      ventriculo-peritoneal shunts were inserted 1 week post-operatively. In view of
      the benign nature of the tumour, no adjuvant radiotherapy or chemotherapy was
      given. OUTCOME: There was no further tumour growth or clinical deterioration over
      a 6-year follow-up period.

PMID- 15565451
TI  - Use of a compact intraoperative low-field magnetic imager in pediatric
      neurosurgery.
AB  - OBJECT: The majority of investigations on the utility of and indications for
      intraoperative magnetic resonance imaging (iMRI) have been in adult patients. We
      report our initial experience utilizing low-field iMRI in pediatric patients.
      METHODS: We performed 21 procedures on 20 patients aged 2 months to 18 years
      (mean 8.9 years) utilizing the PoleStar -10 iMRI system. The procedures included
      15 craniotomies, 2 shunts, and 1 each of the following surgeries:
      transsphenoidal, craniotomy/transsphenoidal, cranioplasty, and endoscopic biopsy
      and fenestration. Treated lesions included low-grade astrocytoma (5),
      craniopharyngioma (3), cortical dysplasia (3), hydrocephalus (2), and others (8).
      The number of scans ranged from 2 to 5 with a mean of 3.2. Intraoperative imaging
      and navigation provided valuable information on the extent of resection and
      catheter placement. In eight procedures it influenced the surgical strategy. No
      untoward events attributable to the system occurred. CONCLUSIONS: The low-field
      PoleStar -10 iMRI system can safely assist pediatric neurosurgeons treating a
      variety of diseases. In addition to neuronavigation it provides information on
      extent of resection, real-time guided catheter placement, and avoidance of
      complications.

PMID- 15565453
TI  - Flexible dose-response models for Japanese atomic bomb survivor data: Bayesian
      estimation and prediction of cancer risk.
AB  - Generalised absolute risk models were fitted to the latest Japanese atomic bomb
      survivor cancer incidence data using Bayesian Markov Chain Monte Carlo methods,
      taking account of random errors in the DS86 dose estimates. The resulting
      uncertainty distributions in the relative risk model parameters were used to
      derive uncertainties in population cancer risks for a current UK population.
      Because of evidence for irregularities in the low-dose dose response, flexible
      dose-response models were used, consisting of a linear-quadratic-exponential
      model, used to model the high-dose part of the dose response, together with
      piecewise-linear adjustments for the two lowest dose groups. Following an assumed
      administered dose of 0.001 Sv, lifetime leukaemia radiation-induced incidence
      risks were estimated to be 1.11 x 10(-2) Sv(-1) (95% Bayesian CI -0.61, 2.38)
      using this model. Following an assumed administered dose of 0.001 Sv, lifetime
      solid cancer radiation-induced incidence risks were calculated to be 7.28 x 10(
      2) Sv(-1) (95% Bayesian CI -10.63, 22.10) using this model. Overall, cancer
      incidence risks predicted by Bayesian Markov Chain Monte Carlo methods are
      similar to those derived by classical likelihood-based methods and which form the
      basis of established estimates of radiation-induced cancer risk.

PMID- 15565454
TI  - Primary intraocular lymphoma: a review of the clinical, histopathological and
      molecular biological features.
AB  - INTRODUCTION: Primary intraocular lymphoma (PIOL) is a rare non-Hodgkin lymphoma
      which arises in the retina or the vitreous. It can occur either together with or
      independently of primary cerebral nervous system lymphoma (PCNSL); the incidence
      of the latter has significantly increased over the past three decades. PIOL
      remains one of the most difficult diagnoses to establish, particularly due to its
      ability to mimic other diseases in the eye and to the limited material which is
      often available for examination. METHODS: The article reviews the clinical,
      histopathological, molecular biological and biochemical approaches to the
      diagnosis of PIOL. The differential diagnoses, including other lymphomatous
      manifestations in the eye, e.g. primary uveal lymphoma, as well as non-neoplastic
      uveal diseases are addressed. Furthermore, the treatment strategies for PIOL are
      summarised. RESULTS: Diagnostic progress has been made in various fields,
      including flow cytometry and immunocytology, cytokine analysis, and as well as
      molecular biological analysis of the immunoglobulin heavy and light chains using
      polymerase chain reaction on both fixed and non-fixed material. The optimal
      therapy of PIOL remains to be determined: the current trends suggest that
      combined radiotherapy and chemotherapy, as well as intravitreal chemotherapy, are
      of value. Novel therapies which may have a role in the future include oral
      trofosfamide. CONCLUSION: Our understanding of the pathogenesis of PIOL/PCNSL
      remains far from complete. Intensified efforts must be made to determine the cell
      of origin of PIOL, as well as to establish "molecular signatures", which could be
      used to decrease diagnostic delay. Further studies, possibly prospective ones,
      are required to establish the optimal therapy for initial and recurrent disease.

PMID- 15565456
TI  - Allogeneic hematopoietic cell transplantation: from experimental biology to
      clinical care.
AB  - PURPOSE: For more than half a century, researchers have explored myeloablative,
      high-dose chemo/radiotherapy followed by allogeneic hematopoietic stem cell
      transplantation (HCT) for therapy of malignant and nonmalignant hematological
      diseases. Continuous advances in the field have changed this approach from one
      that was initially thought to be fraught by insurmountable complications to one
      that is now considered standard therapy for many diseases. METHODS: In order to
      extend allogeneic HCT to include elderly patients, who represent the main
      population affected by hematological malignancies, and to those who are medically
      unfit to undergo conventional HCT, novel non-myeloablative approaches have been
      developed. These approaches rely on graft-vs-tumor effects for tumor eradication
      rather than high-dose chemoradiotherapy, and, accordingly, have lower toxicities
      than conventional regimens. RESULTS: Results with non-myeloablative regimens have
      been gratifying, and this may change the future of allogeneic HCT. Advances could
      not have been possible without basic research and studies in pre-clinical animal
      models. CONCLUSION: Further work is focused on improving graft-vs-tumor effects
      while achieving better control of graft-vs-host disease.

PMID- 15565457
TI  - A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression
      and invasive phenotype of gastric cancer.
AB  - PURPOSE: Matrix metalloproteinase-9 (MMP-9, gelatinase B) plays a key role in
      cancer invasion and metastasis by degradating the extracellular matrix (ECM) and
      basement membrane barriers. A cytosine (C)-thymidine (T) single nucleotide
      polymorphism (SNP) at position -1562 in the MMP-9 promoter is reported to affect
      expression of this gene. The purpose of this study was to investigate the
      relation between the -1562 C/T polymorphism and the development and progression
      of gastric cancer. METHODS: The study population included 177 gastric cancer
      patients and 224 healthy control subjects. The SNP in the MMP-9 promoter was
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and sequencing. Genotype frequencies were compared between patients
      and controls, and the association of genotypes with clinicopathological features
      was studied. RESULTS: Genotype frequencies in gastric cancer patients were
      similar to those in control subjects (P = 0.223). However, significant
      association was found between degree of tumor invasion, clinical stage, and
      lymphatic invasion and the MMP-9 polymorphism in gastric cancer patients (P<0.05,
      for each). CONCLUSIONS: Our results indicate that the T allele in the MMP-9
      promoter is associated with the invasive phenotype of gastric cancer.

PMID- 15565458
TI  - Continuous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an
      antiangiogenic therapy of glioblastoma multiforme.
AB  - PURPOSE: Glioblastoma multiforme (GBM) represents the prototype of an angiogenic
      tumor. Recently, the continuous low-dose scheduling of chemotherapeutic drugs in
      combination with an inhibition of cyclooxygenase-2 (COX-2) has been suggested as
      a novel anti-angiogenic approach. The aim of this study was to evaluate the
      safety and activity of continuous low-dose temozolomide (TMZ) plus the COX-2
      inhibitor rofecoxib in patients with newly diagnosed GBM. METHODS: In vitro,
      endothelial cells were characterized by a tenfold higher sensitivity to TMZ than
      glioma cells. Consequently, a subgroup of patients with incompletely resected GBM
      (n=13) was divided into three groups aiming at a dose escalation to 1/10 of the
      daily MTD for TMZ: (A) TMZ 10 mg/m2 every third day and rofecoxib 25 mg/d; (B)
      TMZ 10 mg/m2/d and rofecoxib 25 mg/d; (C) TMZ 5 mg/m2 twice a day and rofecoxib
      12.5 mg twice a day. COX-2, VEGF, VEGF Receptor-2, and CD34 were assessed
      immunohistochemically, in the clinical setting. RESULTS: The mean follow-up
      period was 15 months. We observed no severe toxicity attributable to the therapy.
      Quality of life was not impaired. For the whole study population, median time to
      progression and overall survival were 8 months and 16 months, respectively.
      Immunohistochemistry suggested that tumors with higher vessel densities were
      characterized by a significantly better control than those with lower vessel
      densities. CONCLUSIONS: Continuous low-dose TMZ plus rofecoxib is feasible, safe,
      and maintains good quality of life. This study is indicative of an anti
      angiogenic efficacy of continuous low-dose TMZ plus rofecoxib in GBMs, especially
      in those tumors that are characterized by a high angiogenic activity.

PMID- 15565460
TI  - Associations between fish reproductive cycle and the dynamics of metazoan
      parasite infection.
AB  - The parasite fauna of the stone loach (Barbatula barbatula) was investigated
      monthly from May to December 2001. Four parasite species were recorded:
      Gyrodactylus spp. (Monogenea), Tylodelphys clavata (Digenea), Proteocephalus
      sagittus (Cestoda), and Raphidascaris acus (Nematoda). The changes in the
      seasonal dynamics of parasite infection were investigated throughout the 8
      months. The potential effect of the reproductive investment of the host, measured
      by gonad mass and gonado-somatic index (GSI), on the parasite infection was
      tested against the prediction that, during periods of high reproductive
      investment (beginning of the breeding period or forming gonads after breeding),
      the fish are more susceptible to parasite infection. Differences between parasite
      loads between genders were also hypothesized. Seasonal differences in infection
      were observed for all parasite species studied. The values of GSI showed a
      pattern of energy accumulation in the pre-reproductive period and at the
      beginning of breeding, a decrease during breeding, and an increase in the post
      breeding period. A similar pattern was observed for parasite abundance, a strong
      or weak increase in spring and/or autumn and a decrease during summer (July and
      August). Positive correlations between the abundance of Gyrodactylus spp. and R.
      acus and both gonad mass and GSI were found in females after eliminating the
      effect of fish weight. Our results suggest that stone loach females are more
      susceptible to parasite infection in periods of higher reproductive investment.
      The main factor determining the infection of T. clavata was fish size. The
      abundance of P. sagittus was positively correlated with GSI in the total fish
      sample with no detectable effect of sex or fish weight. The increase in cestode
      infection in spring supports the hypothesis that the parasite life cycle could by
      synchronized with the beginning of host reproduction, probably induced by
      increasing fish hormone levels in the spring.

PMID- 15565459
TI  - Increased expression of ADAM family members in human breast cancer and breast
      cancer cell lines.
AB  - PURPOSE: ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane
      bound cell surface glycoproteins, which have numerous functions in cell growth,
      differentiation, and motility. We wished to investigate the expression of ADAM 9,
      10, 12, 15, and in human breast cancer. METHODS: Expression of ADAMs was
      determined in breast cancer specimens and the corresponding non-neoplastic breast
      tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines
      via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM
      antibodies on cell proliferation were assessed by measuring DNA-synthesis.
      RESULTS: Breast cancer tissue samples showed increased mRNA expression of ADAM 9,
      12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein
      expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7
      and MDA-MB453 cell lines, with the highest expression levels being observed for
      ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies
      significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast
      cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be
      stimulated by the administration of anti-ADAM 12 antibody. CONCLUSION: The
      results of this study suggest that ADAMs are differentially expressed in human
      breast cancer and are capable of modulating tumour cell growth.

PMID- 15565461
TI  - Parasitic helminths of reptiles (Reptilia) in South Moravia (Czech Republic).
AB  - An helminthological investigation of 104 reptile species was carried out in south
      Moravia (Czech Republic). We examined Lacerta viridis, L. agilis, Anguis
      fragilis, Natrix natrix, Coronella austriaca and Vipera berus. Twelve species of
      parasites were found. Among these, Nematoda occurred most often, followed by
      Trematoda and Cestoda. No Acanthocephala were detected.

PMID- 15565462
TI  - Seasonal dynamics of the fecal excretion of Elaphostrongylus cervi (Nematoda,
      Metastrongyloidea) first-stage larvae in Iberian red deer (Cervus elaphus
      hispanicus) from southern Spain.
AB  - Elaphostrongylus cervi (Nematoda, Metastrongyloidea) is an extrapulmonary
      lungworm of red deer (Cervus elaphus) whose first-stage larvae (L1) require
      terrestrial gastropods as intermediate hosts. The seasonal pattern of fecal
      excretion of E. cervi L1 in Iberian red deer (Cervus elaphus hispanicus) was
      monitored during three annual periods (June 2000-May 2003) on a hunting estate
      from south-central Spain. The lowest rates of mean intensity of fecal L1 were
      found in summer, whereas no seasonal variation was found for prevalence. Monthly
      intensity of excretion was positively associated with early rainfall (the next
      month) rather than with rainfall of the same month. This seasonal rhythm of E.
      cervi L1 discharge may be the result of parasite adaptation to the seasonal
      Mediterranean climate and habitat constraints to improve the chance of parasite
      transmission. We have standardized the sampling period to compare E. cervi L1
      infection rates of Iberian red deer populations in Mediterranean Spain, a natural
      limit of both the parasite and deer historical ranges, for potential use in the
      assessment of management strategies.

PMID- 15565463
TI  - Resistance against eye flukes: naive versus previously infected fish.
AB  - A central issue in fish production is the influence of parasitic infections on
      fish health in fish farms and on survival prospects after fish-stocking into the
      wild. Is it preferable to produce fish in infection-free conditions or to allow
      some infection to elicit resistance in fish? We explored the infection of totally
      naive and previously infected rainbow trout (Oncorhynchus mykiss) by the
      trematode parasite Diplostomum spathaceum in laboratory conditions. We found that
      up to 86.1% of the presented cercariae became established in the lenses of naive
      fish, which indicated that these fish were highly susceptible to infection and
      that innate resistance served little or no protection against the parasite.
      However, acquired resistance after initial infection decreased parasite
      establishment by 85.0-89.1%. Parasite establishment was also affected by fish
      host density as fewer parasites were found in fish in higher densities. The
      implications of these results for the fish-farming industry and fish-stocking
      protocols are discussed.

PMID- 15565464
TI  - An SXP/RAL-2 protein produced by the subventral pharyngeal glands in the plant
      parasitic root-knot nematode Meloidogyne incognita.
AB  - Meloidogyne incognita is a major parasite of numerous plant families, including
      many crop species. Upon infection of the plant root, it induces several
      multinucleate giant cells by the injection of pharyngeal gland secretions into
      the root cells. In order to obtain a better understanding of the nematode-plant
      interaction, characterization of the pharyngeal gland secretions is a necessity.
      By differential display, a nematode gene was identified that encodes a new member
      of the SXP/RAL-2 protein family. The gene is specifically expressed in the
      subventral pharyngeal glands and the protein is most likely secreted.

PMID- 15565465
TI  - A new description of the reproductive system of Schistosoma mansoni (Trematoda:
      Schistosomatidae) analyzed by confocal laser scanning microscopy.
AB  - Classical schemes of the adult Schistosoma mansoni reproductive system have been
      described. In our study, whole adult worms derived from unisexual or mixed
      infections and stained with carmine chlorine were virtually and tomographically
      analyzed under confocal laser scanning microscopy. We found that: (1) there were
      morphological differences in the ovary, vitteline glands and testicular lobes
      between specimens derived from unisexual or mixed infections; (2) there was
      always a single lobed ovary (three or four lobes), presenting differentiation
      from the anterior to the posterior lobes, where the most mature oocytes were
      located; (3) the proximal segment of oviduct was connected to an ampullary
      dilatation, full of tailed spermatozoa, characterizing a seminal receptacle; (4)
      there was no long vitelline duct, but a short one that begins at the end of the
      proximal region of the vitelline gland; (5) long cells of Mehlis' gland placed
      radially around the ootype were not observed. Otherwise, the ootype was only
      lined by thick cuboidal epithelial cells with plaited bases and nuclei with
      flabby chromatin, making a clear distinction from the uterine epithelium. This
      morphological feature suggests that each cell represents a gland. (6) In coupled
      males, the specimens located inside the gynaecophoric canal had smaller
      testicular lobes, suckers, and body length and width when compared to their
      partners. Our results show that the reproductive system does not follow a unique
      pattern within flatworms. Due to its better resolution, confocal laser scanning
      microscopy, using a reflected mode with tomographic sections, allows new
      interpretations, modifying the adopted and current descriptions of the internal
      morphological structures of S. mansoni adult worms.

PMID- 15565466
TI  - Isolation and diversity analysis of resistance gene analogues (RGAs) from
      cultivated and wild strawberries.
AB  - Degenerate oligonucleotide primers, designed based on conserved regions of
      Nucleotide Binding Site (NBS) domains from previously cloned plant resistance
      genes, were used to isolate Resistance Gene Analogues (RGAs) from wild and
      cultivated strawberries. Seven distinct families of RGAs of the NBS-LRR type were
      identified from two related wild species, Fragaria vesca and F. chiloensis, and
      six different Fragaria x ananassa cultivars. With one exception (GAV-3), the
      deduced amino acid sequences of strawberry RGAs showed strong similarity to TIR
      (Toll Interleukin I Receptor)-type R genes from Arabidopsis, tobacco and flax,
      suggesting the existence of common ancestors. GAV-3 seemed to be more closely
      related to the non-TIR type. Further studies showed that the recombination level
      and the ratio of non-synonymous to synonymous substitutions within families were
      low. These data suggest that NBS-encoding sequences of RGAs in strawberry are
      subject to a gradual accumulation of mutations leading to purifying selection,
      rather than to a diversifying process. The present paper is the first report on
      RGAs in strawberry.

PMID- 15565468
TI  - Gene symbol: ALAS2. Disease: sideroblastic anaemia.

PMID- 15565467
TI  - Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith
      Magenis syndrome.
AB  - Smith-Magenis syndrome (SMS) is a mental retardation/multiple congenital
      anomalies disorder associated with a heterozygous approximately 4-Mb deletion in
      17p11.2. Patients with SMS show variability in clinical phenotype despite a
      common deletion found in >75-80% of patients. Recently, point mutations in the
      retinoic acid induced 1 (RAI1) gene, which lies within the SMS critical interval,
      were identified in three patients with many SMS features in whom no deletion was
      detected. It is not clear if the entire SMS phenotype can be accounted for by
      RAI1 haploinsufficiency, nor has the precise function of RAI1 been delineated. We
      report two novel RAI1 mutations, one frameshift and one nonsense allele, in
      nondeletion SMS patients. Comparisons of the clinical features in these two
      patients, three of the previously reported RAI1 point mutation cases, and the
      patients with a common deletion suggest that the majority of the clinical
      features in SMS result from RAI1 mutation, although phenotypic variability exists
      even among the individuals with RAI1 point mutations. Bioinformatics analyses of
      RAI1 and comparative genomics between human and mouse orthologues revealed a zinc
      finger-like plant homeo domain (PHD) at the carboxyl terminus that is conserved
      in the trithorax group of chromatin-based transcription regulators. These
      findings suggest RAI1 is involved in transcriptional control through a multi
      protein complex whose function may be altered in individuals with SMS.

PMID- 15565469
TI  - Molecular heterogeneity of the dystrophin-associated protein complex in the mouse
      kidney nephron: differential alterations in the absence of utrophin and
      dystrophin.
AB  - The dystrophin-associated protein complex (DPC) consisting of syntrophin,
      dystrobrevin, and dystroglycan isoforms is associated either with dystrophin or
      its homolog utrophin. It is present not only in muscle cells, but also in
      numerous tissues, including kidney, liver, and brain. Using high-resolution
      immunofluorescence imaging and Western blotting, we have investigated the effects
      of utrophin and dystrophin gene deletion on the formation and membrane anchoring
      of the DPC in kidney epithelial cells, which co-express utrophin and low levels
      of the C-terminal dystrophin isoform Dp71. We show that multiple, molecularly
      distinct DPCs co-exist in the nephron; these DPCs have a segment-specific
      distribution and are only partially associated with utrophin in the basal
      membrane of tubular epithelial cells. In utrophin-deficient mice, a selective
      reduction of beta2-syntrophin has been observed in medullary tubular segments,
      whereas alpha1-syntrophin and beta1-syntrophin are retained, concomintant with an
      upregulation of beta-dystroglycan, beta-dystrobrevin, and Dp71. These findings
      suggest that beta2-syntrophin is dependent on utrophin for association with the
      DPC, and that loss of utrophin is partially compensated by Dp71, allowing the
      preservation of the DPC in kidney epithelial cells. This hypothesis is confirmed
      by the almost complete loss of all DPC proteins examined in mice lacking full
      length utrophin and all C-terminal dystrophin isoforms (utrophin(0/0)/mdx(3Cv)).
      The DPC thus critically depends on these proteins for assembly and/or membrane
      localization in kidney epithelial cells.

PMID- 15565470
TI  - Expression of neuronal markers suggests heterogeneity of chick sympathoadrenal
      cells prior to invasion of the adrenal anlagen.
AB  - We have analyzed the distribution of neural crest-derived precursors and the
      expression of catecholaminergic and neuronal markers in developing adrenal tissue
      of chick embryos. Undifferentiated neural crest cells are found in presumptive
      adrenal regions from embryonic day 3 (E3) onward. An increasing proportion of
      cells expressing tyrosine hydroxylase (TH) mRNA indicates catecholaminergic
      differentiation of precursors not only in primary sympathetic ganglia, but also
      in presumptive adrenal regions. Whereas precursors and differentiating cells show
      mesenchymal distribution until E5, discrete adrenal anlagen form during E6. Even
      during E5, catecholaminergic cells with low or undetectable neurofilament M (NF
      M) mRNA expression prevail in positions at which adrenal anlagen become distinct
      during E6. The predominance of TH-positive and NF-M-negative cells is maintained
      throughout embryogenesis in adrenal tissue. RNA encoding SCG10, a pan-neuronal
      marker like NF-M, is strongly expressed throughout adrenal anlagen during E6 but
      is found at reduced levels in chromaffin cells compared with neuronal cells at
      E15. Two additional neuronal markers, synaptotagmin 1 and neurexin 1, are
      expressed at low to undetectable levels in developing chromaffin cells throughout
      embryogenesis. The developmental regulation of neuronal markers shows at least
      three different patterns among the four mRNAs analyzed. Importantly, there is no
      generalized downregulation of neuronal markers in developing adrenal anlagen.
      Thus, our observations question the classical concept of chromaffin
      differentiation from a common sympathoadrenal progenitor expressing neuronal
      properties and suggest alternative models with changing instructive signals or
      separate progenitor populations for sympathetic neuronal and chromaffin endocrine
      cells.

PMID- 15565471
TI  - Demonstration of vertebral and disc mechanical torsion in adolescent idiopathic
      scoliosis using three-dimensional MR imaging.
AB  - This study was designed to demonstrate and measure mechanical torsion in patients
      with adolescent idiopathic scoliosis using three-dimensional magnetic resonance
      (MR) imaging. Ten patients with adolescent idiopathic scoliosis were imaged with
      three-dimensional MR imaging, and the data post-processed through multiplanar
      reconstruction to produce images angled through individual endplates. Transverse
      rotation was measured at each endplate and these measurements used to calculate
      the amount of vertebral and disc mechanical torsion present. A test object was
      imaged in order to validate the measurement technique. Mechanical torsion was
      demonstrated within the vertebral bodies and discs of the imaged subjects, with
      vertebral mechanical torsion contributing on average 45% of the overall
      transverse plane deformity. It is concluded that deformation occurs in the
      transverse plane within the vertebrae and discs of subjects with idiopathic
      scoliosis, and a significant proportion of the rotation present in the scoliotic
      spine occurs as a result of plastic deformation within the vertebrae themselves.
      We believe that this is the first systematic demonstration of mechanical torsion
      in idiopathic scoliosis.

PMID- 15565472
TI  - Health related quality of life in patients with Parkinson's disease two years
      following posteroventral pallidotomy.
AB  - BACKGROUND: There has been a new emphasis on the use of health related quality of
      life (HRQOL) measures for translating how a patient's response to treatment is
      experienced by the patient. The purpose of this study was to describe patient
      reported HRQOL two years after surgery in subjects who underwent posteroventral
      pallidotomy (PVP) for the treatment of Parkinson's disease (PD) and a subset of
      these same subjects four years following PVP. METHOD: A consecutive series of 52
      subjects who were evaluated previously, prior to and at 4 months following PVP
      [3], received long term follow-up using mailed questionnaires. Twenty seven
      subjects (52% of the original sample) provided 2 year follow-up data and 15 of
      these subjects (29%) provided 4 year follow-up data. Severity of disease and
      subject reported HRQOL were evaluated. FINDINGS: Immediately following surgery,
      there was a sharp decrease in all measures of severity of disease. While there
      were differing patterns of increasing severity of disease among the measures
      following the immediate postoperative assessment, all of the measures remained
      better than the pre-surgery values. The data showed a pattern of marked
      improvement in HRQOL at 4 months following PVP. Over the 2 years following
      surgery, there was a gradual deterioration toward preoperative levels that
      nevertheless remained better than preoperative HRQOL. For the group with data at
      4 years following surgery, there was no significant further deterioration in
      HRQOL between 2 and 4 years, with the 4 year data also remaining better than the
      preoperative HRQOL reports. CONCLUSIONS: In spite of advanced severe PD and
      advanced age, subjects in this study reported better HRQOL at 2 years following
      PVP than they reported at entry into the study prior to surgery. Additionally,
      the 15 patients who were available for follow-up at 4 years also reported better
      HRQOL than they experienced prior to the surgery.

PMID- 15565473
TI  - Trichilemmal cyst involving the skull base.
AB  - BACKGROUND: Trichilemmal cyst (TC) a rare tumour originating from the outer root
      sheath of the hair follicle particularly in the scalp has never been reported to
      involve the skull base. Here a case of TC extensively involving the skull base is
      presented. The neuro-imaging, operative, and pathological features are described.
      Possible histogenesis is also discussed. METHOD: The clinical, radiological,
      operative, and pathological features of a TC involving the temporal-infratemporal
      fossae, orbit, paranasal sinuses, and the clivus is described. FINDINGS:
      Multilocular cysts full of keratinized material were found. Histopathological
      findings were consistent with those for a typical cutaneous TC. CONCLUSION: TC of
      the variety found in the skin may involve the skull base extensively where it
      shows the typical histopathological features.

PMID- 15565474
TI  - Infected CNS infusion pumps. Is there a chance for treatment without removal?

PMID- 15565477
TI  - Assessment of effects of pinealectomy and exogenous melatonin administration on
      rat sciatic nerve suture repair: an electrophysiological, electron microscopic,
      and immunohistochemical study.
AB  - BACKGROUND: Collagen scar formation at the cut end of a nerve, an important
      problem in clinical practice for neurosurgeons in peripheral nerve surgery,
      obstructs sprouting of axons into appropriate distal fascicles, and thereby
      limits nerve regeneration. Researchers attempt to control collagen accumulation
      in the formation of neuroma by various physical and chemical methods, but these
      have yielded only limited functional success. This is the first experimental
      study investigating the effects of melatonin (MLT) on nerve repair and neuronal
      regeneration in rat sciatic nerve suture repair. METHODS: The hypothesis that
      exogenous MLT administration may inhibit the formation of neuroma in peripheral
      nerve surgery was investigated in rat sciatic nerve model. In this study, a total
      of 80 rats were used for control groups (Groups Ia, Ib, IIa, and IId), MLT group
      (Group Ic), surgical pinealectomy (Px) groups (Groups IIb and IIc), and group of
      MLT treatment following Px procedure (Group IIe). All animals underwent a
      surgical intervention consisting of bilateral sciatic nerve section and primary
      suture repair. At 8 weeks after repair, the animals were killed following
      completion of recording of nerve action potentials (NAPs). Then, unilateral
      sciatic nerve specimens including the suture repair region were carefully removed
      and the excised segments were processed for electron microscopy examination.
      Afterwards, contralateral sciatic nerve specimens from two animals from each
      group were removed and stained for immunohistochemical analysis. RESULTS: Results
      of morphometric analysis revealed that Px procedure caused an elevation of
      collagen content of the sciatic nerve and macroscopic neuroma formation, and that
      there was a statistically significant reduction in collagen content of the same
      region in pinealectomized animals treated with MLT (p<0.001). Accordingly,
      electrophysiological findings demonstrated that the stimulus intensities required
      to excite a NAP response were increased in surgical Px group, but the presence of
      a reduced threshold response was found in the group treated with MLT following Px
      procedure (p<0.01). Immunohistochemical staining for Type I collagen and Type III
      collagen was markedly more intense in the epineurium of animals after Px.
      Virtually no or only weak staining was observed in animals in control groups and
      the MLT treatment group. Results of immunohistochemical analysis revealed that
      surgical Px procedure caused a strong immunoreactivity for Type I collagen and
      Type III collagen in all connective tissue planes of the nerve, especially in the
      epineurium, and there was a statistically significant reduction in
      immunoreactivity of the repair region in animals receiving MLT treatment after Px
      procedure (p<0.001). CONCLUSION: This study demonstrates that exogenous MLT
      administration significantly inhibits collagen accumulation in the formation of
      neuroma in the suture repair site and thereby improves nerve regeneration. From a
      clinical standpoint, the positive effect of MLT administration on neuroma
      formation and nerve regeneration seems a particularly attractive treatment
      option. Therefore, we believe that nerve repair with addition of MLT may be a
      worthwhile option in addition to other treatment modalities in case of MLT
      deficiency, such as aging. However, further experimental and clinical studies
      using functional analysis warranted to confirm this result in future.

PMID- 15565478
TI  - Microsurgical anatomy of the dorsal cervical rootlets and dorsal root entry
      zones.
AB  - BACKGROUND: Detailed anatomical knowledge of the dorsal cervical rootlets and
      dorsal root entry zones (DREZ) is important for the diagnosis and treatment of
      cervical myeloradiculopathy and surgical management of pain. There are far fewer
      micro-anatomical studies of this area than gross anatomical studies. This study
      presents several anatomical points regarding the dorsal cervical rootlets and
      dorsal root entry zones. METHOD: Fifteen adult formalin-fixed cadaveric spines
      from C1 to T1 were used to observe the posterior structures. They were studied
      under the surgical microscope following en bloc laminectomy and foraminotomy. The
      morphological features of the dorsal root entry zones and dorsal rootlets were
      determined. The distance from the midline to the DREZ, the longitudinal length of
      the DREZ in the spinal canal, the length of the dorsal rootlets, the number of
      dorsal rootlets and the intersegmental anastomoses between the dorsal rootlets
      were measured. FINDINGS: The distance from the midline to the DREZ ranged from
      1.1 to 4.7 mm. Longitudinal length of the dorsal rootlets ranged 4.3-17.7 mm. The
      shortest length of the dorsal rootlets ranged between 5-28 mm, and longest
      lengths of the dorsal rootlets ranged 6.8-30.3 mm. The number of dorsal rootlets
      ranged from 2-13. Between the C2-T1 dorsal rootlets, 142 connections out of 30
      intersegments were noted. CONCLUSIONS: The distance from the midline to the DREZ
      decreased in the lower cervical spine. The longest longitudinal length of the
      DREZ was at the C5 level. The length of the dorsal rootlets was increased in the
      lower cervical spine. The average number of dorsal rootlets tended to increase in
      the lower cervical spine. Anastomoses were most often found between C6-7 and C5-6
      dorsal rootlets. Knowledge of the anatomical features of dorsal cervical rootlets
      and dorsal root entry zones is essential for a surgeon to avoid injuring the
      neural structures. This knowledge is a must not only to avoid complications but
      also for the success, safety and effectiveness of microsurgical operations of the
      pathological conditions like posterior myeloradiculopathy and pain treatment such
      as DREZ operations.

PMID- 15565479
TI  - Oedema formation in experimental photo-irradiation therapy of brain tumours using
      5-ALA.
AB  - BACKGROUND: Five-aminolevulinic acid (5-ALA) induces the specific accumulation of
      photosensitising porphyrins in malignant gliomas and has been explored for photo
      irradiation therapy of these tumours. However, information is unavailable on
      whether and to what extent this treatment modality may induce the formation of
      brain oedema, and how potential oedema might be treated. METHODS: Rats were
      implanted with C6 gliomas. Eight days later magnetic resonance images (MRI) were
      obtained. On day 9 rats received 100 mg 5-ALA/kg b.w. and were craniotomized for
      photo-irradiation of tumours 6 hours later (100 J/cm2, 635 nm argon-dye laser).
      Part of the animals was treated with daily dexamethasone injections (0.3 mg/kg),
      beginning 6 hours before phototherapy. 72 hours later, brains were removed and
      dissected according to tumour dimensions on pre-therapy MRI into "tumour", "brain
      around tumour" (BAT), residual cortex and basal ganglia, for measurements of
      water contents. Measurements were also performed in untreated animals with
      tumours, with or without steroid treatment and in control animals. An additional
      group of animals lacking tumours, with or without steroid treatment, underwent 5
      ALA-phototherapy to determine effects on normal brain. RESULTS: C6 gliomas
      induced brain oedema, which responded to steroid treatment. 5-ALA-phototherapy
      resulted in additional oedema, which responded partly to steroids. 5-ALA
      phototherapy of normal brain increased water content moderately in irradiated
      cortex. This oedema was also partly counteracted by steroids. CONCLUSIONS: Photo
      irradiation therapy with 5-ALA induces oedema which is partly counteracted by
      steroid therapy. The possibility of steroid resistant oedema formation should be
      considered when planning human trials with this treatment modality.

PMID- 15565480
TI  - A comparison of different grading scales for predicting outcome after
      subarachnoid haemorrhage.
AB  - BACKGROUND: Most scales used to assess prognosis after subarachnoid haemorrhage
      (SAH) are based on the level of consciousness of the patient. Based on
      information from a logistic regression model, Ogilvy et al. developed a new
      grading scheme (Massachussetts General Hospital (MGH) Scale) which applied a
      simple scoring method to each prognostic factor considered relevant such as level
      of consciousness, age, quantity of blood in the first CT scan and size of the
      aneurysm. The purpose of this study is to introduce a modified version of the MGH
      scale, built up using factors applicable to every patient suffering SAH, and
      compare this new scale to the World Federation of Neurological Surgeons scale
      (WFNS), the Glasgow Coma Scale (GCS) scale for SAH and the MGH scale. METHOD: A
      series of 442 patients consecutively admitted to Hospital 12 de Octubre between
      January 1990 and September 2001 with the diagnosis of spontaneous SAH were
      retrospectively reviewed. Outcome was assessed by means of the Glasgow Outcome
      Scale measured six months after hospital discharge. Differences between grades of
      the WFNS, the GCS scale for SAH, the MGH scale and the new scale were computed by
      chi2 statistics. ROC curves were plotted for the different scales and their areas
      compared. FINDINGS: Both WFNS and GCS scales fail to present significant
      differences between most of their grades, while the proposed scale shows a
      constant inter-grade significant difference in predicting outcome. The proposed
      scale presents a significantly higher prognostic efficacy in the whole series of
      patients suffering spontaneous SAH, patients with idiopathic subarachnoid
      haemorrhage (ISAH) and patients with confirmed aneurysmal SAH. The MGH scale is
      not applicable to some groups of patients suffering SAH. INTERPRETATION: Grading
      scales including additional factors to the level of consciousness show higher
      prognostic efficacy. The proposed modification of the MGH scale makes it
      applicable to every patient suffering SAH without losing its prediction
      capability.

PMID- 15565481
TI  - Prevention of external ventricular drain--related ventriculitis.
AB  - OBJECTIVE: The purpose of this study was to test if a reduction of external
      ventricular drains (EVD) related ventriculitis could be achieved by a strict
      protocol of care and if protocol violation was associated with a higher incidence
      of EVD-related ventriculitis. METHODS: A written protocol for EVD insertion,
      nursing and surveillance was implemented. A retrospective comparison of EVD
      related ventriculitis incidence was performed between control (161 EVD in 131
      patients) and study periods (216 EVD in 175 patients). Risk factor analysis was
      performed in patients in whom an EVD was inserted during the study period
      including the relationship between protocol compliance and ventriculitis. A score
      for the number of protocol violations (absence of hair clipping, absence of a
      tunnelled EVD, absence of shampooing, incorrect dressing change, inappropriate
      CSF bag or tap samplings and EVD manipulation) was established for each patient.
      RESULTS: Incidence of patient-related ventriculitis decreased from 12.2% (1999)
      down to 5.7% (p<0.05) as well as incidence of EVD-related ventriculitis (9.9% vs
      4.6%, p<0.05). During the study period, the only statistically significant risk
      factors for infection were CSF leak and protocol violations. The mean protocol
      violation score was 4 times higher in the infected versus the non-infected
      patients (p<0.0001). Patients with a violation score of 0 or 1 had no infection
      (EVD duration 2 to 42 days). CONCLUSION: EVD can be left safely, as long as
      needed, provided that meticulous care is taken for EVD insertion and nursing. EVD
      duration seems to have no effect on infection incidence.

PMID- 15565482
TI  - Spontaneous subdural haematoma in anabolic steroids dependent weight lifters:
      reports of two cases and review of literature.
AB  - Spontaneous subdural haematoma is very rare in young patients. The complications
      of anabolic steroid intake in weight lifters are numerous, yet subdural
      haematomas have not been reported. We report on two cases of spontaneous subdural
      haematomas in young weight lifters. Both patients underwent surgical evacuation
      and made a full recovery. A review of the literature on the complications
      associated with valsalva manoeuvres is also presented including hemodynamic and
      intracranial changes. We propose that patients on chronic anabolic steroids may
      have vascular changes that predispose them to bleeding during a Valsalva
      manoeuvre (VM).

PMID- 15565483
TI  - Single-stage operation for bilateral middle cerebral artery aneurysms.
AB  - BACKGROUND: Subarachnoid haemorrhage with bilateral middle cerebral artery
      aneurysms is occasionally encountered in neurosurgical practice. We report upon
      our experiences of the single-stage operation for bilateral middle cerebral
      artery aneurysms (BMCA) through a bilateral subfrontal approach. METHODS: During
      the past two and half years, we have experienced three cases of BMCAA, who were
      treated by this method. The whole procedure was conducted using a single-stage
      head positioning and draping. Slight table tilting was enough to allow the proper
      clipping of each aneurysm. FINDINGS: During the past 2.5 years, 255 cases of
      intracranial aneurysm have been treated in our hospital. Among these, the
      incidence of BMCAA was 1.18% (3/255). The mean duration of operation for the
      three cases involved was 5.8 hours, and showed a progressive decrease with
      experience. All patients recovered well, and were discharged as in other
      uneventful aneurysm cases. The total operation time was longer, and was a little
      more laborious than normal single aneurysm surgery. CONCLUSION: This method has
      substantial advantages over "classical" skull base approaches to MCA aneurysms.
      As extensive frontal lobe manipulation and external facial incisions are avoided
      with subfrontal approaches, intensive care unit and overall hospital stay are
      reduced, related complications are minimized, and postoperative cosmetic
      appearance is enhanced.

PMID- 15565484
TI  - Cervical spinal cord stimulation increases cerebral cortical blood flow in an
      experimental cerebral vasospasm model.
AB  - BACKGROUND: Cerebral microcirculatory changes during cerebral vasospasm after
      aneurysmal subarachnoid haemorrhage (SAH) are still controversial and uncertain.
      The aim of our study is to demonstrate that spinal cord stimulation (SCS)
      augments cerebral cortical microcirculatory blood flow in an experimental
      cerebral vasospasm model by using Laser Doppler Flowmetry (LDF). METHOD: The
      experiments were carried out on 24 New Zealand rabbits. Three experimental groups
      were designed. In group 1, Cerebral cortical blood flow (CCoBF) was evaluated by
      LDF in 8 rabbits. In group 2, Intracisternal saline injection and cervical
      epidural electrode placement without SCS were performed in 8 animals before LDF.
      In group 3, LDF was performed before and after SCS on the 4th day of SAH in 8
      rabbits. CCoBF parameters obtained from LDF data were compared. FINDINGS: The
      occurrence of vasospasm after SAH was demonstrated with significant changes in
      LDF values. In all SAH animals, SCS resulted in significant increase
      (approximately 30%) in CCoBF. This increase was observed to continue even after
      the cessation of the stimulation. CONCLUSIONS: These results indicate that SCS
      improves cortical ischemia due to vasospasm after induced SAH. The cervical SCS
      may constitute a new therapeutic modality in treating disturbed CCoBF due to
      vasospasm.

PMID- 15565485
TI  - Image guided interstitial laser thermotherapy: a canine model evaluated by
      magnetic resonance imaging and quantitative autoradiography.
AB  - OBJECTIVE: To determine the applicability and safety of a new canine model
      suitable for correlative magnetic resonance imaging (MRI) studies and
      morphological/pathophysiological examination over time after interstitial laser
      thermotherapy (ILTT) in brain tissue. MATERIAL AND METHODS: A laser fibre (Diode
      Laser 830 nm) with an integrated temperature feedback system was inserted into
      the right frontal white matter in 18 dogs using frameless navigation technique.
      MRI thermometry (phase mapping i.e. chemical shift of the proton resonance
      frequency) during interstitial heating was compared to simultaneously recorded
      interstitial fiberoptic temperature readings on the border of the lesion. To
      study brain capillary function in response to ILTT over time quantitative
      autoradiography was performed investigating the unidirectional blood-to-tissue
      transport of carbon-14-labelled alpha amino-isobutyric acid (transfer constant K
      of AIB) 12, 36 hours, 7, 14 days, 4 weeks and 3 months after ILTT. RESULTS: All
      laser procedures were well tolerated, laser and temperature fibres could be
      adequately placed in the right frontal lobe in all animals. In 5 animals MRI
      based temperature quantification correlated strongly to invasive temperature
      measurements. In the remaining animals the temperature fibre was located in the
      area of susceptibility artifacts, therefore, no temperature correlation was
      possible. The laser lesions consisted of a central area of calcified necrosis
      which was surrounded by an area of reactive brain tissue with increased
      permeability. Quantitative autoradiography indicated a thin and spherical blood
      brain barrier lesion. The magnitude of K of AIB increased from 12 hours to 14
      days after ILTT and decreased thereafter. The mean value of K of AIB was 19 times
      (2 times) that of normal white matter (cortex), respectively. CONCLUSION: ILTT
      causes transient, highly localised areas of increased capillary permeability
      surrounding the laser lesion. Phase contrast imaging for MRI thermomonitoring can
      currently not be used for reliable temperature readings in vivo. The suggested
      new canine model proved to be safe, accurate, easy to use, and provides clinical,
      radiographic, pathological and physiological correlations.

PMID- 15565486
TI  - Correlation of continuously monitored regional cerebral blood flow and brain
      tissue oxygen.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      continuously monitored regional cerebral blood flow (CBF) and brain tissue oxygen
      (PtiO2). METHODS: Continuous advanced multimodal neuromonitoring including
      monitoring of PtiO2 (Licox, GMS) and CBF (QFlow, Hemedex) was performed in eight
      patients after severe subarachnoid haemorrhage (n=5) and traumatic brain injury
      (n=3) for an average of 9.6 days. Parameters were measured using a flexible
      polarographic PtiO2-probe and a thermal diffusion CBF-microprobe. FINDINGS:
      Regarding the whole monitoring period in all patients, the data indicated a
      significant correlation between CBF and PtiO2 (r=0.36). In 72% of 400 analysed
      intervals of 30 minutes duration with PtiO2 changes larger than 5 mmHg, a strong
      correlation between CBF and PtiO2 existed (r>0.6). In 19% of intervals a still
      statistically significant correlation was observed (0.3<r<0.6). During the
      remaining 9% no correlation was found (r<0.3). Regarding the clinical stability
      of the monitoring devices, the CBF monitoring system allowed monitoring of CBF in
      64% of the time when PtiO2 monitoring was possible only. Phases of non-monitoring
      were mostly due to fever of the patient, when the system does not allow
      monitoring to avoid overheating of the cerebral tissue. CONCLUSIONS: This study
      suggests a correlation between CBF and PtiO2. The level of PtiO2 seems to be
      predominately determined by regional CBF, since changes in PtiO2 were correlated
      in 90% of episodes to simultaneous changes of CBF.

PMID- 15565488
TI  - Interactions between riluzole and conventional antiepileptic drugs -- a
      comparison of results obtained in the subthreshold method and isobolographic
      analysis.
AB  - The exact types of pharmacodynamic interactions between riluzole and conventional
      antiepileptic drugs were evaluated in two available ways, the subthreshold and
      isobolographic analysis. Maximal electroshock test in mice was used as an animal
      model for generalized tonic-clonic convulsions. In the first method, riluzole
      (1.25-2.5 mg/kg) significantly raised the electroconvulsive threshold in mice.
      The drug administered at its subprotective dose of 0.3125 mg/kg enhanced the
      antiseizure activity of carbamazepine and phenobarbital, while, when applied at
      the higher dose of 0.625 mg/kg, it potentiated also the action of valproate and
      diphenylhydantoin. Riluzole (0.625) alone and in combinations with antiepileptic
      drugs did not produced any motor or log-term memory deficit. Results obtained
      from isobolographic analysis determined pure additive interaction between
      riluzole and all used conventional antiepileptic drugs. Since riluzole did not
      change plasma concentrations of co-administered antiepileptics, pharmacokinetic
      interactions, at least in terms of their free plasma levels, do not seem
      probable. The results of the present study confirm significant antiseizure
      properties of riluzole in the model of generalized tonic-clonic epileptic
      attacks. Moreover, comparison of effects obtained from both methods evaluating
      drug interactions strongly indicates a crucial role of the isobolographic
      analysis in verification and supplementation data achieved from the subthreshold
      method.

PMID- 15565489
TI  - Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier
      and causes seizure independently by glutamate release.
AB  - Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces
      seizures and convulsion in elder and renal failure patients. However, beta
      lactams are known not to pass through the blood-brain barrier (BBB). In this
      study, we examined the BBB penetration of cefoselis in normal and renal failure
      rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in
      brain extracellular fluid in proportion to its blood level. The elimination
      constant from brain extracellular fluid (apparent) was slightly lower than that
      from blood. These results indicated that cefoselis might penetrate the BBB or be
      discharged by a certain transport system. In contrast to the result of cefoselis,
      cefazolin, a leading drug of cephalosporins, could not be detected in the brain
      extracellular fluid after an intravenous injection. In renal dysfunction rats,
      the elimination half-lives of cefoselis from both blood and brain were
      extensively prolonged. This would be one of responsible factors inducing seizures
      seen in patients. However, the additional factor, such as decrease in brain
      function related to aging, would be involved in seizures in patient received
      cefoselis, because an extremely high dose was required to induce seizures even in
      renal failure rats. A local administration of cefoselis into the hippocampus
      through the microdialysis probe caused a striking elevation of extracellular
      glutamate, with a minimum increase in gamma-aminobutyric acid (GABA). However, a
      systematic cefoselis administration via the tail vein did not elevate
      extracellular glutamate and GABA concentrations in the hippocampus of renal
      failure rats that exhibited marked seizures. These results suggested that not the
      stimulation of glutamate release, but the blockade of GABA receptors might be
      responsible for the seizure induced by cefoselis.

PMID- 15565490
TI  - Differential expression of glutamate transporters EAAT1 and EAAT2 in mice
      deficient for PACAP-type I receptor.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates
      glutamatergic neurotransmission and induces the expression of glutamate
      transporters EAAT1 and EAAT2 in newborn mouse astroglial cell cultures. Since
      nanomolar concentrations of PACAP exert this effect, signal transduction via the
      high affinity PACAP-type I-receptor PAC1 was assumed. To test this hypothesis and
      to assess the importance of PAC1-signalling in vivo, we analyzed glutamate
      transporter expression in mice with a PAC1 knockout. EAAT1 and EAAT2 expression
      was investigated in the hippocampus and the cerebral cortex of PAC1 mutant mice
      and wildtype littermates by semiquantitative in-situ-hybridization. PAC1-knockout
      mice show a subtle but significant reduction of EAAT1 expression in the dentate
      gyrus. In contrast, reduced expression levels of EAAT1 in the cerebral cortex did
      not reach statistical significance and EAAT2 expression was unchanged in CA3 and
      cerebral cortex of PAC1 mutant mice. Our data confirm the previously reported in
      vitro-regulation of EAAT1 in the adult nervous system in vivo. EAAT2 expression,
      however, is unchanged in PAC1 knockout mice, most likely due to counterbalancing
      factors.

PMID- 15565491
TI  - PET neuroimaging and mutations in the DJ-1 gene.
AB  - Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism.
      We performed F-DOPA and FDG PET neuroimaging in two parkinsonism patients
      homozygous for DJ-1 mutations, three relatives heterozygous for a DJ-1 mutation
      and one non-carrier, all from the originally described kindred from The
      Netherlands. Their characteristics were compared to those of typical Parkinson's
      disease patients and healthy controls. Both parkinsonism patients had reduced F
      DOPA uptake concordant with typical Parkinson's disease. In the, clinically
      unaffected, heterozygous relatives, F-DOPA metabolism was unremarkable, thus not
      suggesting a dosage effect of the DJ-1 gene.

PMID- 15565492
TI  - Reduced GSK-3beta mRNA levels in postmortem dorsolateral prefrontal cortex of
      schizophrenic patients.
AB  - Glycogen Synthase Kinase (GSK)-3 is a ubiquitous serine/threonine protein kinase
      highly abundant in brain which plays a key role in neural development and neuron
      survival. We have previously reported that GSK-3beta protein levels and GSK-3
      activity are reduced by over 40% in postmortem prefrontal cortex of schizophrenic
      patients compared to patients with bipolar illness, unipolar depression and to
      normal controls, and Emamian et al. have recently presented convergent evidence
      for impaired AKT1-GSK-3beta signaling in schizophrenia. Using specimens of
      dorsolateral prefrontal cortex tissue obtained from The Stanley Medical Research
      Institute's Brain Collection, from the same subjects used previously, we now show
      that GSK-3beta, but not GSK-3alpha, mRNA levels are 36% lower in the patients
      with schizophrenia compared to all other comparison groups. The present study
      lends further support to the finding of low GSK-3beta levels in schizophrenia and
      extends this observation by suggesting that the decrease in GSK-3beta may be due
      to reduced protein synthesis possibly due to altered transcriptional drive of the
      GSK-3beta gene.

PMID- 15565493
TI  - DRD4 receptor gene exon III polymorphism in inpatient suicidal adolescents.
AB  - Some studies have suggested possible association of the dopamine receptor subtype
      4 (DRD4) gene exon III 48 bp repeat polymorphism with novelty seeking behavior.
      As suicidal behavior in adolescents is linked to risk taking behavior, we
      evaluated the association of suicidality with DRD4 polymorphism in Israeli
      inpatient suicidal adolescents. Sixty-nine inpatient adolescents who recently
      attempted suicide were assessed by structured interview and rating scales for
      detailed clinical history, diagnoses, suicide intent and risk, impulsivity,
      violence, and depression. The frequency of DRD4 alleles was compared between the
      suicidal inpatients and 167 healthy control subjects. No significant association
      between the DRD4 polymorphism and suicidal behavior was found. Analysis of the
      suicide-related measures demonstrated a significant difference in depression
      severity between suicidal inpatients homozygote and heterozygote for the DRD4
      alleles (p=0.003). The relevance of this finding to increased depression severity
      in suicidal adolescents, if replicated, is as yet unclear.

PMID- 15565494
TI  - A controlled study of tryptophan and cortisol in violent offenders.
AB  - Changes in the metabolism of tryptophan, other amino acids, and steroid hormones
      have been implicated in aggression. We compared tryptophan, competing long amino
      acids (CAAs), and cortisol in serum (S) and CSF in 22 violent offenders and 15
      healthy controls. Offenders had significantly increased S-L-tryptophan, S-free
      tryptophan, S-CAAs, S-cortisol and CSF-cortisol, indicating abnormal
      neurophysiological processes. Larger studies on the interplay between violence,
      serotonin precursors, and stress hormones need to integrate personality traits,
      life situations, and physiological adaptation.

PMID- 15565495
TI  - Homocysteine associated genomic DNA hypermethylation in patients with chronic
      alcoholism.
AB  - Higher plasma homocysteine concentrations can influence genomic DNA methylation
      in peripheral blood cells. In the present controlled study we observed a
      significant increase (10%) of genomic DNA methylation in patients with alcoholism
      (t = -3.16, df = 158, p = 0.002) which was significantly associated with their
      elevated homocysteine levels (multiple linear regression, p < 0.001). Since
      methylation of DNA is an important epigenetic factor in regulation of gene
      expression these findings may have important implications for a possible
      subsequent derangement of epigenetic control these patients.

PMID- 15565496
TI  - In search of neurophysiological markers of pervasive developmental disorders:
      smooth pursuit eye movements?
AB  - Genetic studies of autism would benefit from the identification of
      (neurophysiological) markers of the disease. Reports that subjects with autism
      suffer from abnormalities of visual motor processing, indicate that abnormalities
      in smooth pursuit eye movements (SPEM) may be a marker of the disorder. Sixteen
      high-functioning school-aged children with pervasive developmental disorder (PDD)
      were compared with a matched group of eighteen normally developing controls on
      performance of a SPEM task and a task which tested the integrity of visually
      guided saccadic eye movements. Both groups of children had normal eye movements
      during performance of these tasks. Thus abnormalities in SPEM would appear not to
      be a marker of PDD. The earlier reported abnormalities in visual motion
      processing might need to be reinterpreted.

PMID- 15565498
TI  - Catalytic activity, stability, unfolding, and degradation pathways of engineered
      and reconstituted myoglobins.
AB  - The structural and functional consequences of engineering a positively charged
      Lys residue and replacing the natural heme with a heme-L-His derivative in the
      active site of sperm whale myoglobin (Mb) have been investigated. The main
      structural change caused by the distal T67K mutation appears to be mobilization
      of the propionate-7 group. Reconstitution of wild-type and T67K Mb with heme-L
      His relaxes the protein fragment around the heme because it involves the loss of
      the interaction of one of the propionate groups which stabilize heme binding to
      the protein. This modification increases the accessibility of exogenous ligands
      or substrates to the active site. The catalytic activity of the reconstituted
      proteins in peroxidase-type reactions is thus significantly increased,
      particularly with T67K Mb. The T67K mutation slightly reduces the thermodynamic
      stability and the chemical stability of Mb during catalysis, but somewhat more
      marked effects are observed by cofactor reconstitution. Hydrogen peroxide, in
      fact, induces pseudo-peroxidase activity but also promotes oxidative damage of
      the protein. The mechanism of protein degradation involves two pathways, which
      depend on the evolution of radical species generated on protein residues by the
      Mb active species and on the reactivity of phenoxy radicals produced during
      turnover. Both protein oligomers and heme-protein cross-links have been detected
      upon inactivation.

PMID- 15565499
TI  - Survival of patients with SLE admitted to an intensive care unit-a retrospective
      study.
AB  - We examined the demography, reasons for admission and cause of death in systemic
      lupus erythematosus (SLE) patients admitted to a medical intensive care unit
      (ICU) over a 7-year period. Fourteen patients were admitted during this period
      all were female, 13 were of mixed ethnic ancestry and one a black South African.
      Of the 14 patients, 12 were admitted as a result of lupus activity, 2 had sepsis
      as the major cause of admission, although 5 other patients developed infection
      during their admission. Five patients had a generalised flare of their disease or
      progressive renal failure. Seven patients were admitted with a variety of lupus
      related pathologies. In general the precise cause of death was difficult to
      determine. Of the 14 patients, 9 had impaired renal function on admission
      including 1 with sepsis and 1 of the survivors. Three patients (21%) survived,
      one with respiratory failure due to shrinking lung, a second with an acute flare
      of SLE and a third with pulmonary emboli. This study demonstrates that lupus in
      our community may produce life-threatening flares. Although cause of death was
      not always definitely identified, admission to the ICU was primarily due to
      active SLE and not sepsis or iatrogenic disease.

PMID- 15565501
TI  - Molecular dynamics in nanophase-separated comb-like poly(alpha-n-alkyl beta-L
      aspartate)s.
AB  - A series of poly(alpha-n-alkyl beta-L-aspartates) which are nanophase self
      assembled comb-like polymers has been studied by dielectric spectroscopy in a
      broad frequency range (10(-2) < or = nu < or = 3 x 10(6) Hz), with n-alkyls side
      chains of various lengths, 10 < or = n < or =18. In every member of the series
      the same relaxations were identified after the decomposition of the experimental
      isothermal trace in up to three peaks with relaxation times distributions. The
      strength, width and average relaxation time for all the relaxation modes were
      determined for each material. Besides the local low temperature, Arrhenius modes,
      two relaxation modes, alpha and alpha(PE), present a cooperative character whose
      dynamics are not affected by the side chains melting. The alpha(PE) relaxation is
      a polyethylene-like glass transition of the amorphous side chains and its
      dynamics is strongly dependent on the n value due to the increasing restrictions
      imposed by the self-assembled confinement. The strength of the alpha(PE)
      relaxation mode increases as the lateral chains loose their 2D order. The
      restricted chopstick motion of the rigid rods is thought to be the origin of the
      alpha mode; this motion is hindered at temperatures where the cage size decreases
      as a result of the increasing disorder with temperature.

PMID- 15565500
TI  - Radiation-induced intracranial meningiomas: review of six operated cases.
AB  - It is well known that radiation can induce meningiomas. These tumors usually
      arise in patients with a history of low-dose radiation to the scalp for treatment
      of tinea capitis or high-dose radiation for a previous brain tumor. Radiation
      associated meningiomas (RAMs) morphologically resemble their spontaneously
      arising counterparts. However, RAMs frequently present a more malignant phenotype
      and, as such, are diagnosed as "atypical" or "aggressive" meningiomas and occur
      predominantly in younger patients. This paper describes six cases of radiation
      associated intracranial meningiomas in patients previously treated with low-dose
      radiation to the scalp for tinea capitis.

PMID- 15565502
TI  - Elastic consequences of a single plastic event: a step towards the microscopic
      modeling of the flow of yield stress fluids.
AB  - With the eventual aim of describing flowing elasto-plastic materials, we focus
      here on the elementary process of such a flow, a plastic event, and compute the
      long-range perturbation it elastically induces in a medium submitted to a global
      shear strain. We characterize the effect of a nearby wall on this perturbation,
      and quantify the importance of finite-size effects. Although most of our explicit
      formulae refer to 2D situations, our statements hold for 3D situations as well.

PMID- 15565503
TI  - Accelerated dynamic Fourier velocity encoding by exploiting velocity-spatio
      temporal correlations.
AB  - OBJECTIVE: To describe how the information content in a Fourier velocity encoding
      (FVE) scan can be transformed into a very sparse representation and to develop a
      method that exploits the compactness of the data to significantly accelerate the
      acquisition. MATERIALS AND METHODS: For validation, fully sampled FVE datasets
      were acquired in phantom and in vivo experiments. Fivefold and eightfold
      acceleration was simulated by using only one fifth or one eighth of the data for
      reconstruction in the proposed method based on the k-t BLAST framework.
      Reconstructed images were compared quantitatively to those from the fully sampled
      data. RESULTS: Velocity spectra in the accelerated datasets were comparable to
      the spectra from fully sampled datasets. The detected peak velocities remained
      accurate even at eightfold acceleration, and the overall shape of the spectra was
      well preserved. Slight temporal smoothing was seen in the accelerated datasets.
      CONCLUSION: A novel technique for accelerating time-resolved FVE scan is
      presented. It is possible to accelerate FVE to acquisition speeds comparable to a
      standard time-resolved phase-contrast scan.

PMID- 15565505
TI  - American Academy Of Asthma, Allergy & Immunology - 58th Annual Meeting. 1-6 March
      2002, New York, City, NY, USA.

PMID- 15565506
TI  - Rituximab and alefacept. 1-6 March 2002, New York City, NY, USA.

PMID- 15565504
TI  - Contrast enhancement in atherosclerosis development in a mouse model: in vivo
      results at 2 Tesla.
AB  - To develop an MRI method for the evaluation of contrast enhancement in early
      atherosclerotic plaque development in the abdominal aorta of a mouse model. Male
      apoE-/- mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4)
      weeks were included. Axial T1 spin echo images of the abdominal aorta were
      obtained above and below the renal arteries (90 microm spatial resolution) before
      and over 1 h after the injection of a macromolecular contrast agent. Signal
      enhancement was measured in the vessel wall and compared to histological
      features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min
      post injection. During this time, the signal-to-noise ratio increased by a factor
      up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively.
      The enhancement of the arterial wall appeared less pronounced in the oldest mice,
      16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium
      agent, contrast uptake in atherogenesis varies with lesion stage and may be
      related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful
      to evaluate the atherosclerotic plaque activity in mice.

PMID- 15565507
TI  - Facing the ragweed challenge. 1-6 March 2002, New York City, NY, USA.

PMID- 15565508
TI  - Gene transfer and transcription factors. 1-6 March 2002, New York City, NY, USA.

PMID- 15565509
TI  - Beeson Gregory and Weil Gotshal & Manges cancer therapies conference and
      exhibition 2002. 20 February 2002, London, UK.

PMID- 15565510
TI  - Angiogenesis and anti-angiogenesis therapeutics. 20-21 February 2002, London, UK.

PMID- 15565511
TI  - Retroviruses and opportunistic infections - ninth conference. New antiviral
      agents. 24-28 February, Seattle, WA, USA.

PMID- 15565512
TI  - HDL Cholesterol - Third Annual International Conference. Metabolic Pathways and
      Drug Development. 25-26 February 2002, Boston, MA, USA.
AB  - This meeting, organized by The Knowledge Foundation Inc, brought together leading
      scientists from industry and academia and focused on therapeutic targets for
      patients with low levels of high density lipoprotein (HDL) cholesterol, for whom
      optimal therapies are lacking. The conference sessions included: (i) the genetics
      of rare and common HDL disorders; (ii) the role of ATP-binding cassette
      transporter A1 in reverse cholesterol transport; (iii) the influence of the HDL
      modifying enzymes, cholesteryl ester transfer protein (CETP), lipoprotein lipase,
      and hepatic lipase on HDL metabolism and atherosclerosis susceptibility; (iv)
      recent advances in research of scavenger receptor BI; (v) the role of nuclear
      receptors in the regulation of cholesterol and HDL metabolism; and, (vi) new drug
      targets for raising HDL. From the data presented, it was clear that a great deal
      of progress has been made in recent years with regard to our understanding of HDL
      metabolism and reverse cholesterol transport. This has ultimately led to the
      generation of promising new targets for the treatment of patients with HDL
      deficiency.

PMID- 15565513
TI  - NFkappaB: Bench to Bedside - Keystone Symposium. 25 February - 3 March 2002,
      Keystone, CO, USA.

PMID- 15565514
TI  - Genomic Partnering - Fifth Annual CHI Meeting: emerging and early-stage
      companies. Genome Tri-Conference. 23-24 February 2002, Santa Clara, CA, USA.
AB  - The 2002 Genome Tri-Conference was a medium-sized meeting, with an approximate
      attendance of 400 to 500 delegates. This event held three conferences back to
      back, addressing three different aspects of current developments in the area of
      genomics, ie, genomic partnering, human genome discovery and gene functional
      analysis. Several new aspects of genomics, such as clinical genomics and chemical
      genomics, were discussed.

PMID- 15565515
TI  - Malaria's Challenge: from infants to genomics to vaccines - Keystone Symposium. 3
      8 March 2002, Keystone, CO, USA.

PMID- 15565516
TI  - Malarial proteinases: a review of the recent patent literature.
AB  - Malaria remains one of the most serious diseases worldwide, and increasing and
      widespread resistance against available antimalarial therapeutics calls for the
      discovery and development of novel therapeutic strategies. Malarial proteinases
      represent an attractive and alternative drug target. The life cycle of the
      Plasmodium parasites that cause malaria depends on proteinolytic degradation of
      hemoglobin, and intervention in that process has been shown to be curative in
      animal models. The current progress towards novel malarial proteinase inhibitors,
      as documented in the patent literature, will be discussed in this review.

PMID- 15565517
TI  - Cancer multidrug resistance: a review of recent drug discovery research.
AB  - Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting
      multidrug resistance (MDR), caused by changes in the level or activity of
      membrane transporters that mediate energy-dependent drug efflux and of other
      proteins that affect drug metabolism and/or drug action. Many inhibitors of MDR
      transporters have been identified and some are undergoing clinical trials, but
      currently none are in clinical use. Here we briefly review the status of MDR
      drugs, outline novel approaches designed to suppress or circumvent MDR mechanisms
      and discuss the future of MDR therapy in oncology.

PMID- 15565518
TI  - Vitrase ISTA Pharmaceuticals.
AB  - Vitrase is under development by ISTA Pharmaceuticals Inc (formerly Advanced
      Corneal Systems, ACS) and Otsuka Pharmaceutical (in Japan) for the potential
      treatment of vitreous hemorrhage and diabetic retinopathy. In November 1998, it
      was approved in Mexico for the clearing of vitreous hemorrhage [305542]. In
      October 1998, Vitrase was designated a Fast-Track product for the vitreous
      hemorrhage indication by the FDA [303024], [307576]. The initial section of an
      NDA was filed in January 2002, which comprised the non-clinical pharmacology and
      toxicology sections [434925]. In April 2002, following discussions with the FDA,
      ISTA reported that it would be proceeding with the preparation and submission of
      the clinical and other required sections of the NDA for Vitrase for the treatment
      of vitreous hemorrhage [447148]. In February 2002, analysts at CIBC World Markets
      Corp predicted Vitrase would be launched in early 2003, with worldwide sales
      reaching 200 million dollars within 5 years [444945].

PMID- 15565519
TI  - Drotrecogin alfa Eli Lilly.
AB  - Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant
      developed and launched by Eli Lilly & Co for the treatment of sepsis [333781],
      [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris
      for drotrecogin alfa in June 2001. This trade name had been proposed by Lilly in
      place of the previous brand name, Zovant, which was deemed unacceptable by the
      EMEA due to concerns that the name could be confused with hospital-based drugs
      [412512]. Filings for sepsis were made in the US, EU and Australia in February
      2001 [398514], [447870] and in March 2001, the US FDA assigned drotrecogin alfa
      Priority Review status [403435]. The FDA extended the action date from July 27 to
      October 27, 2001 for completion of its review of the biologics license
      application (BLA) for drotrecogin alfa to assess further supplementary data
      submitted by Lilly [412512]. At the October 16, 2001 meeting (postponed from
      September 12), the FDA Advisory Committee on Anti-Infective Drugs split 10 to 10
      over whether to recommend approval [425873], [425940]. In late October 2001,
      Lilly received an approvable letter from the FDA for the treatment of severe
      sepsis. Approval was contingent upon successful negotiation of labeling,
      agreement on post-approval clinical trials, and successful completion of
      manufacturing inspections [427301]. In November 2001, the FDA approved
      drotrecogin alfa for the reduction of mortality in adult patients with severe
      sepsis who have a high risk of death [430133]; the product was launched onto the
      US market days later [436271]. Following the FDA committee's split decision in
      October 2001, Credit Suisse First Boston, which expected mid-2002 approval but
      with restrictive labeling, revised its predictions from $1.265 billion in 2004
      sharply downwards to $543 million [425929].

PMID- 15565520
TI  - [Evaluation of the accessibility of stroke units in Poland].
AB  - BACKGROUND AND PURPOSE: According to the World Health Organization (WHO)
      assumptions every patient with a stroke should be treated by a specialized stroke
      team or in a specialized stroke unit. The aim of our study was to evaluate the
      accessibility and eligibility of stroke units in Poland. MATERIALS AND METHODS:
      We have developed a questionnaire evaluating the structure and staff of
      neurological departments. The questionnaire was sent to all neurological
      departments in Poland in the last quarter of 2003. We grouped the departments in
      5 categories: having a stroke unit of class A (fulfilling the criteria of the
      Experts of the National Program of Prevention and Treatment of Stroke
      guidelines), class B (conditionally fulfilling the criteria), class C (not
      fulfilling the criteria), departments having stroke units without a separate
      structure and departments without stroke units. The classification was shown to
      each provincial consultant in order to verify our data in January 2004. RESULTS:
      We have received replies from 194 of 222 (87.4%) departments. 97 departments
      declared having a stroke unit: 20 -- class A, 56 -- class B, 14 -- class C and 7 
      - stroke units without a separate structure. The remaining 97 departments do not
      have any stroke units. The most frequent problem that plays a role in the
      classification of departments was the deficit of staff or equipment. CONCLUSIONS:
      The stroke unit network in Poland is developing dynamically, but a significant
      number of the existing stroke units need more diagnostic equipment, staff and
      structural changes.

PMID- 15565521
TI  - [Epidemiological aspects of multiple sclerosis in Lublin (Poland)].
AB  - BACKGROUND AND PURPOSE: The objective of this paper was to present an
      epidemiological analysis of multiple sclerosis (MS) in Lublin, identify MS
      prevalence as well as characterize the population of MS patients. MATERIAL AND
      METHODS: Information about the patients was gathered and they were examined from
      1996 to the end of 2000, that is within a 5-year period. The patients' data were
      obtained from the neurological departments in Lublin, most often neurological
      (but also general and ophthalmic) clinics, as well as from the Lublin MS Society.
      The remaining patients' data were obtained from the doctors, family members, the
      Lublin MS Society members, as well as from the hospital and clinic files. The
      patients were interviewed in detail using a prepared questionnaire. The diagnosis
      and its degree of certainty were determined in accordance with the Poser's
      criteria. The control group included 111 healthy people who were Lublin residents
      on the day of examination. The obtained results were analyzed in epidemiological
      and statistical terms. RESULTS: On the prevalence day (31 December 1997) there
      were 204 MS cases in Lublin, including 141 women (69%) and 63 men (31%). The
      calculated incidence ratio was 57.3/105. The average age of MS onset was
      estimated to be 30.1 years. On 31 December 1997 the average duration of the
      illness was 15.4 years. The average age for the examined cases was 45.5 years.
      The average DSS (Disability Status Scale) score was 3.5. Most often the disease
      began with a single symptom, in 155 cases (75.9%), whereas several symptoms
      occurred in 37 patients (18.1%). The most common symptoms at the illness onset
      were sensory impairments (52 patients), optic neuritis (42 people) and pyramidal
      symptoms (34 patients). The most common form of the illness was a disseminated
      form, which was diagnosed in 131 patients (64.2%). In the examined patient
      population four types of MS were recognized. The relapsing-remitting MS (RR-MS)
      was observed in 62 patients (30.3%), the secondary progressive MS (SP-MS) in 83
      patients (40.6%), and the primary progressive MS (PP-MS) was characteristic of 40
      people (19.6%), while 19 patients (9.3%) experienced a benign course of MS.
      CONCLUSIONS: Our results are typical for the region of high incidence of MS. They
      are similar to the data achieved in other populations of that region.

PMID- 15565522
TI  - [Analysis of expression of estrogen (ER) and progesterone receptors (PR) in brain
      glial tumors and its correlation with expression of p53 protein and proliferating
      cell nuclear antigen (PCNA)].
AB  - BACKGROUND AND PURPOSE: All the types of the glial cells contain estrogen (ER)
      and progesterone receptors (PR) but their occurrence in glial tumors of the brain
      is still controversial. The aim of this research was the clinical analysis of ER
      and PR expression in correlation with histological malignancy and expression of
      p53 and PCNA. MATERIAL AND METHODS: The investigation was carried out on a group
      of 56 patients operated on at the Neurosurgical Department of Wroclaw Medical
      University. The percentage of tumors containing ER and PR was assessed and mean
      receptor expressions were compared. Classical histological tests,
      immunohistochemical tests for ER, PR, p53 and PCNA with monoclonal antibodies
      (DACO) were performed for every specimen of tumor tissue. RESULTS: ER occurred in
      24 cases (42.9%), PR in 10 cases (17.9%). 49% of highly malignant gliomas (WHO
      III and IV) were ER positive, whereas 29% of tumors grade I and II were ER
      positive. Frequencies of PR positive tumors were similar in both groups. Mean PR
      expression in p53 positive group was 8% and in p53 negative group 1.5% (p=0.017).
      Mean ER expression in PCNA positive group was 7.4%, whereas in PCNA negative
      group 2.7% (p<0.01). CONCLUSIONS: Frequency of ER occurrence is higher in highly
      malignant tumors. ER expression is correlated with proliferative activity (PCNA).
      PR expression is positively correlated with intensity of mutant p53 protein.

PMID- 15565523
TI  - [SPECT imaging of cerebral arteriovenous angiomas. A preliminary report].
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to demonstrate
      scintigraphic evaluation of cerebral perfusion in patients with intracranial
      hemangiomas. MATERIAL AND METHOD: The examination was carried out in 12 patients
      aged from 12 to 67 years. In all the patients cerebral angiomas were previously
      diagnosed and all of them were qualified for intravascular embolization. Brain
      scintigraphy was performed after IV injection of 99mTcECD and included the
      dynamic phase with images obtained every 2 seconds for 1.5 minutes and SPECT
      imaging. The semiquantitative analysis of regional cerebral blood flow was based
      on the comparison between activity in two symmetrical regions of interest.
      Cerebral angiography combined with intravascular embolization followed the
      scintigraphic examination. RESULTS: Based on angiograms, the size of the nidus
      was estimated at 1.0 to 9.0 cm. In 8 patients the dynamic study showed an
      increased tracer accumulation in the region of angioma. On SPECT images the nidus
      was visualized as focally decreased perfusion in all cases. A decreased tracer
      accumulation in the area adjacent to the nidus was detected in 8 patients. The
      ratio of activity in the region of angioma to activity in normally perfused
      tissue calculated using the semiquantitative analysis was 52% to 89%.
      CONCLUSIONS: SPECT images and dynamic phase of cerebral perfusion scintigraphy
      allow perfusion changes caused by the presence of intracranial angiomas to be
      identified.

PMID- 15565524
TI  - [Cerebral blood flow in patients with various symptoms of hemispatial neglect
      following ischemic stroke].
AB  - BACKGROUND AND PURPOSE: The most common cause of hemispatial neglect (HN) is
      cerebral infarction. It can be induced by lesions in many different regions of
      the right hemisphere. The purpose of this article was to determine the prevalence
      of post-stroke HN, its clinical picture, and neuroanatomical correlates. MATERIAL
      AND METHODS: Forty-six stroke patients with a focal right-hemisphere lesion were
      studied. Neglect in visual domain, assessed with a battery of drawing, line
      bisection and shape cancellation tests, was observed in 20 cases. The single
      photon emission-computed tomography (SPECT) images of the brain were obtained
      with 740 MBq (20 mCi) of Tc-99m-labeled ECD on a triple-headed gamma camera.
      RESULTS: The most sensitive measure of HN was the cancellation test, which all
      neglect patients performed poorly. Twelve patients, classified as mildly
      impaired, showed no significant rightward deviation on line bisection, but they
      showed left visual neglect on the cancellation test. Reverse dissociation was not
      noted. Performance on a clock-drawing test revealed HN only in two patients, who
      showed also evidence of HN on other tests. Thereby, some of the tests seem to be
      more difficult or more sensitive to impairment. The critical area of perfusion
      abnormalities in all neglect patients were frontal lobe and striatum on the
      right. In severe HN, SPECT images evidenced the most extensive hypoperfusion
      throughout the perisylvian region and subcortical structures of the right
      hemisphere. Although parietal cortex was affected in patients with moderate to
      severe HN, it was spared in the rest. CONCLUSIONS: HN was a relatively common
      symptom of vascular right-hemisphere damage (43% of the patient population). HN
      was a complex disturbance in terms of its clinical manifestation and neuroimaging
      correlates. Our findings challenge the classical notion that damage to the
      parietal cortex is critically associated with HN. Instead, our results support
      the model attributing hemispatial neglect to a defect in a cortico-striato
      thalamo-cortical loop. Also, the present study highlights the usefulness of
      cerebral blood flow SPECT imaging as a diagnostic aid in the post-stroke deficits
      of cognition following right-hemisphere damage.

PMID- 15565525
TI  - [Nature of headaches in Kimmerle anomaly].
AB  - BACKGROUND AND PURPOSE: Kimmerle anomaly is an anatomical variant of the first
      cervical vertebra consisting in the presence of an osseous canal in the place of
      a sulcus for the vertebral artery. The aim of our work was to determine the
      nature and frequency of headaches in this anomaly. MATERIAL AND METHODS: A
      hundred and eight patients, 58 females and 50 males at the age of 18-59 years (M.
      36.9 years, SD=9.6) with radiologically verified Kimmerle anomaly were examined.
      A control group comprised 40 healthy subjects at the similar age range. The
      diagnosis of headaches was based on the criteria proposed by the IHS. All the
      patients underwent electrophysiological studies (ENG, EEG and VEP). The results
      were statistically analyzed using a SPSS/PC+ computer system. RESULTS: Headaches
      were reported by 83.3% of patients with Kimmerle anomaly and 15% of controls. The
      total number of 50% of Kimmerle patients appeared to suffer from tension-type
      headaches (T-TH) and nearly 25.6% had headaches of a neurovascular nature.
      Neuralgic headaches were reported by 24.4% of patients. In the control group only
      T-TH occurred. In 72.2% of patients headaches occurred for the first time before
      the age of 40 years. The headaches lasted from a few minutes to several days,
      most frequently from several dozen minutes (43.3% of cases) to a few hours (31.1%
      of cases). Frequency of headaches in a year was high. Headaches were accompanied
      by other complaints like dizziness and vertigo, nausea, drop attacks,
      paresthesia, sight and hearing disturbances and also vegetative symptoms.
      CONCLUSIONS: In patients with radiologically verified Kimmerle anomaly a complex
      of clinical signs develops with prevailing headaches (T-TH, neurovascular
      headaches and neuralgia).

PMID- 15565526
TI  - [Transpedicular reconstruction of vertebral body height with simultaneous
      interbody spondylodesis].
AB  - BACKGROUND AND PURPOSE: Surgical treatment of traumatic spinal injury should
      include fast and complete decompression of spinal cord and radices wits reduction
      of broken vertebral body, restoration of physiological spinal curvatures and
      spondylodesis of injured segments. Restoration of natural spinal curvatures is
      only possible when the height of broken vertebral body is reconstructed. MATERIAL
      AND METHODS: Between 1992 and 2001, 75 patients were operated on because of
      traumatic injuries of thoracolumbar spine in the Ortopaedic and Traumatology
      Department Skubiszewski Medical University of Lublin. 48 patients had broken
      vertebral body reduction with simultaneous filling of bone loss with autogenic
      bone grafts inserted through pediculum. Only in 4 cases posterior spondylodesis
      was carried out on arches and spinous processes. Transpedicular plasty of 44
      broken vertebral bodies was connected with posterior interbody fusion with PLIF
      technique using graft application to interbody space. RESULTS: The operative
      protocol presented above allowed for the height of the anterior vertebral wall to
      be restored on average to 81.5% of the original height. We did not observe either
      fatigue breakage of the screws or screws loosening with kyphosis recurrence. We
      did not note serious postoperative complications, including neurological
      compromise. The operative procedure did not significantly change the neurological
      status of the patients. In 9 cases we noted neurological improvement: usually by
      1 or 2 grades in Frankel's score. CONCLUSIONS: Restoration of the fractured
      vertebral body with bone grafts combined with posterior interbody spondylodesis
      effectively prevents the recurrence of the kyphotic deformation.

PMID- 15565528
TI  - [Circadian rhythms of melatonin of patients with severe traumatic brain injury].
AB  - The study was performed on a group of 5 patients with severe traumatic brain
      injury and in 2 healthy volunteers as the controls. The examination began 2-5
      days after injury. The management of the patients and controls did not affect the
      natural melatonin circadian rhythm. The first result obtained was the
      characteristic nocturnal increase of the melatonin level in the healthy subjects.
      In a group of 5 patients with the severe traumatic brain injury the differences
      between the day and night time were insignificant. The results of the present
      study indicate that the severe brain injury gives rise to serious disturbances of
      the melatonin secretion in the acute posttraumatic period. These disturbances are
      characterized by the absence of the natural melatonin circadian rhythm. Despite
      the small number of patients, the obtained results justify further studies.

PMID- 15565529
TI  - [The beta-amyloid cascade hypothesis: a sequence of events leading to
      neurodegeneration in Alzheimer's disease].
AB  - According to the beta-amyloid cascade hypothesis, the accumulation of beta
      amyloid (Abeta) deposits as amyloid plaques in the patient's brain is the primary
      event in the pathogenesis of Alzheimer's disease (AD). Other neuropathological
      changes such as neurofibrillary tangles (NFTs), synaptic degeneration and
      neuronal cell loss are secondary and appear as a consequence of Abeta deposition.
      Abeta is generated during the proteolytic processing of the beta-amyloid
      precursor protein (APP). The endoproteolysis of APP is catalyzed by alpha-, beta
      , and gamma-secretases. The alpha-secretase pathway releases non-amyloidogenic
      products: sAPPbeta, p3 and C83 peptides. In the beta-secretase pathway, apart
      from the sAPPalpha and C99 fragments also beta-amyloid peptides: Abeta40 and/or
      Abeta42 are generated. Abeta42 is neurotoxic and more hydrophobic than Abeta40,
      thus it has stronger tendency to oligomerize and aggregate. The imbalance between
      Abeta production and Abeta clearance is the basis for the formation of amyloid
      plaques. The majority of known APP and presenilin mutations responsible for
      familial early onset AD affect APP processing causing overproduction of Abeta,
      especially Abeta42. Both extracellular and intracellular accumulation of Abeta
      initiates a cascade of the following events leading to the neurodegeneration:
      synaptic and neuritic injury, microglial and astrocytic activation (inflammatory
      response), altered neuronal ionic homeostasis, oxidative damages, changes of
      kinases/phosphatases activities, formation of NFTs, and finally cell death. In
      this paper, we reviewed recent findings supporting the presented hypothesis.

PMID- 15565530
TI  - [Olfactory glial cells: hope in the treatment of spinal cord injuries].
AB  - Spinal cord injuries (SCI) have been reckoned for many years a serious clinical
      problem. Current strategies of SCI treatment prevent the occurrence of secondary
      injury in the spine (neuroprotection methods) as well as induce the anatomical
      and functional reorganization of intact nerve tracts in the spinal cord due to
      the plasticity of the central nervous system (neurorehabilitation methods). The
      observed functional recovery in patients treated for SCI depends on the severity
      of the injury and not always is satisfying. The elucidation in the last two
      decades of the mechanisms responsible for the induction of regeneration in the
      central nervous system enabled new strategies for SCI treatment to be developed.
      These strategies give an opportunity to obtain clinically-essential recovery of
      motor, sensor and vegetative functions, even in cases of total lesion of the
      spinal cord. The milestone in these studies was the usage of intraspinal
      transplants containing cells with neurotrophic properties, tested on the
      experimental model of rat SCI. Among the transplanted cells special attention
      should be paid to the olfactory ensheathing cells (OEC) on account of their
      unique property to stimulate the central neuroregeneration. In this paper the
      authors present basic characteristics of rat OEC, discuss their neurotrophic
      properties after transplantation into the injured animal spinal cord, as well as
      refer to the first attempts to use human olfactory glial cells in the treatment
      of SCI in humans.

PMID- 15565532
TI  - [The importance of laryngological and phoniatric evaluation at the early stage of
      amyotrophic lateral sclerosis].
AB  - The bulbar symptoms of amyotrophic lateral sclerosis (ALS) include difficulty
      with the management of swallowing, saliva production, aspiration of secretion to
      the air ways and problems with spoken communication. These symptoms originate
      from the malfunction of the face muscles and pharynx sphincters. Patients with
      early symptoms of bulbar ALS are often referred to the otolaryngologist for the
      evaluation and management of dysphagia and dysarthria. The bulbar onset of ALS
      with hypernasality, articulation defects and voice harshness make the
      otolaryngologists the primary diagnostician for these signs. Careful examination
      of the speech quality and morphology as well as the function of vocal cords
      should be undertaken. Once the diagnosis of ALS is made, the otolaryngologist's
      involvement in medical treatment is necessary at different stages of the disease.

PMID- 15565533
TI  - [Restless legs syndrome and periodic limb movements during sleep in a patient
      with obstructive sleep apnea].
AB  - A case of moderate obstructive sleep apnea in which effective treatment with
      continuous positive airway pressure did not reduce excessive daytime sleepiness
      was described. Polysomnography with tibial muscles activity recording revealed
      frequent periodic limb movements in sleep (PLMS) with sleep fragmentation. PLMS
      index was 13.6/h of sleep. Clonazepam combined with iron and magnesium
      supplementation reduced limb movements, excessive daytime sleepiness and improved
      the patient's mood. Causes of PLMS and treatment options are discussed. PLMS and
      restless legs syndrome (RLS) should be considered in the differential diagnosis
      of excessive daytime sleepiness.

PMID- 15565534
TI  - [Difficulties in the diagnosis in the case of subacute paraplegia in a woman with
      Addison-Biermer disease].
AB  - The following paper presents a case of presently rare serious and non-typical
      subacutely progressing neurological complications in Addison-Biermer disease in a
      period before the diagnosis, and effective treatment with vitamin B12 in the
      advanced process of the nervous system impairment. The patient was a 52-year-old
      woman with the following (increasingly severe) symptoms occurring over a period
      of 5 weeks, after an earlier non-related operation: paresis of lower limbs (up to
      paraplegia), slight paresis of upper limbs, sphincters disorder, numbness and the
      loss of sensation in the upper and lower limbs, and finally mental deterioration.
      The woman was admitted to a neurological clinic with the suspected Guillain-Bare
      syndrome. After an interview and medical examination, with the help of some
      additional tests and resulting clinical picture, it was diagnosed as the Addison
      Biermer disorder. A typical treatment was started with vitamin B12 injections,
      with a neurological improvement within a week, and further gradual improvement
      over the following 5 weeks of treatment in the clinic (improvement in the
      strength, sensation in the limbs, functionality of the sphincters, and
      normalization of the cognitive functions). After 2 months of continuous
      pharmacological treatment and physical rehabilitation, the patient started to
      walk with the help of a walker, and after further 2 months, she was able to walk
      on her own with a crutch.

PMID- 15565535
TI  - [Educational objectives in the new interdisciplinary subject "Rehabilitation,
      Physical Medicine, Naturopathic Techniques" under the 9th Revision of the
      Licensing Regulations for Doctors--consensus recommendations of the German
      Society for Rehabilitative Sciences and the German Society for Physical Medicine
      and Rehabilitation].
AB  - In October 2003 the 9 (th) revision of the Federal Medical Training Regulations
      (Approbationsordnung) came into effect. The new compulsory interdisciplinary
      subject "Rehabilitation, Physical Medicine, Naturopathic Treatment" offers the
      opportunity to teach all students in comprehensive concepts of Rehabilitation
      such as the International Classification of Functioning, Disability and Health
      (ICF) of the WHO and the new book 9 of the German Social Code (SGB 9), as well as
      Physical Medicine and Naturopathic Treatment. Since the content of this new
      subject has not been defined up to date a joint task force of the German Society
      of Rehabilitation Science and the German Society of Physical Medicine and
      Rehabilitation was founded in order to recommend teaching standards. As part of
      these teaching standards educational objectives are introduced in this article.
      They should guide the persons in charge of teaching the subject in the medical
      faculties. In some areas the students should acquire profound abilities and
      skills in addition to knowledge. The medical faculties may focus on different
      educational targets according to their individual teaching profile.

PMID- 15565536
TI  - [Teamwork and team success in multi- and interdisciplinary teams in medical
      rehabilitation].
AB  - Multidisciplinary or interdisciplinary team models are often used to describe
      teams in medical rehabilitation. There is only little evidence whether these
      models are used in the daily routine of medical rehabilitation and to what extent
      the quality (team work) and effectiveness (team success) differ between the
      models. For the present study an interview guide was designed to assess the team
      models. In each of the six clinics phone interviews were conducted with one
      member of the management. Data on teamwork and team success were collected with a
      staff questionnaire. The questionnaires were distributed to all employees (n =
      266; response rate n = 127, 48%) of the six teams. Two teams were classified as
      interdisciplinary teams and four teams as multidisciplinary. The comparison
      between the two models shows better results for the interdisciplinary team model.
      Several methodical restrictions (e. g. unconsidered moderator variables,
      representativeness of the sample) need to be considered. Systematic analyses of
      teamwork as presented are essential to identify the conditions of successful
      teamwork and also form the basis for implementation of team development measures
      in medical rehabilitation.

PMID- 15565537
TI  - [Inpatient aftercare in rheumatic diseases--concept, trial, and acceptance].
AB  - BACKGROUND: A one-week booster group treatment in rheumatic diseases (rheumatoid
      arthritis, spondylarthropathies, fibromyalgia) was developed in order to
      stabilize rehabilitation effects after medical rehabilitation. The program took
      place in an inpatient setting 3 - 5 months after rehabilitation, aimed at
      refreshing and deepening already learnt contents as well as teaching new subjects
      (e. g. about dietetics). Training and educational elements are given priority in
      this concept. METHOD: A total of 140 patients participated in 19 booster weeks.
      At the end of each booster week the acceptance was assessed by questionnaire and
      in a round-table discussion. RESULTS: Comprehensibility and group atmosphere were
      judged very positively. The course was also considered very helpful, helpfulness
      being rated with marks about 2 (1 = very helpful, 6 = not at all helpful).
      Participants especially appreciated the course's framework as a group setting
      emphasising the exchange of experience with co-patients. At the same time,
      however, participants wished more individualized treatment such as physiotherapy
      or massage. With regard to the quantity of the various therapy elements,
      participants would have preferred more traditional spa therapy, more medical
      treatment by a physician, more group physiotherapy and sports. They would also
      have liked more breaks. In general fewer psychological elements, less discussion
      and reflection but more physical activity was wished for. Little difference was
      found between the various diagnoses, but the program was rated slightly more
      positively by the patients with spondylarthropathies. CONCLUSION: Overall, the
      great number of people participating in the program and their acceptance of the
      booster week are positive. Patients appreciated the group setting and the
      possibilities of exchanging experience on a high level. But it was difficult to
      change patients' traditional expectations concerning medical rehabilitation to a
      behaviour-orientated course like ours. It is worth thinking about whether this
      concept should play a greater role in traditional medical inpatient
      rehabilitation programming.

PMID- 15565538
TI  - [The Osnabruck Work Capabilities Profile (O-AFP) for persons with psychiatric
      illness: concept, development, and testing in schizophrenic patients].
AB  - The goal of this paper is presentation of an inventory for the assessment of
      basic capabilities underlying work and occupational behaviour of psychiatric
      patients in the course of their treatment and rehabilitation. The "Osnabruck Work
      Capabilities Profile" (O-AFP) is an instrument filled in by staff, which consists
      of three scales comprising ten items each, measuring "Learning Ability", "Social
      Communication Ability" and "Adaptation". In the study presented, these scales
      were confirmed by factor analyses of data from 194 schizophrenic patients. Test
      analyses yielded good item and scale characteristics. The only exception to this
      are elevated item difficulty scores of the third scale (adaptation). This was
      attributed to specific effects of selecting the sample of patients. Furthermore,
      low or insignificant correlations with the patients' symptom scores indicate the
      discriminant validity of the scales. It is concluded that the O-AFP is well
      suited for application with different forms of occupational therapy.

PMID- 15565539
TI  - [A set of questionnaires for the assessment (screening) of psychological
      disorders and social problems in cardiac rehabilitation patients].
AB  - A set of questionnaires for the assessment (screening) of psychological and
      social problems in cardiac rehabilitation patients is analyzed for its
      psychometric properties. The test battery had before been consented by a task
      force of the German Association for the Prevention and Rehabilitation of
      Cardiovascular Disease, DGPR. It integrates generally approved and well-tried
      assessments for depression/anxiety, social isolation (vocational) stress, and
      subjective vocational disability. The questionnaire was administered to a
      convenience sample of 426 patients undergoing inpatient cardiac rehabilitation.
      Results on the psychometric properties, a comparison of the cardiac sample to the
      general population, as well as distributions of quartile ranges are reported.
      Also, a preliminary appraisal of the need for further assessment or treatment is
      made. The results confirm that the short test battery is suited for assessing
      psychological and social problems in cardiac rehabilitation patients.

PMID- 15565540
TI  - [Determining the quality of rater judgements using intraclass correlation, and
      enhancing rater judgements].
AB  - In clinical practice ratings by physicians and therapists are among the most
      frequently used assessment procedures. It is shown, which statistical measures
      should be used to assess the reliability of such ratings. Additionally, potential
      causes of insufficient reliability are presented. Improvement of rating quality
      may be achieved by rater training, which is based on an analysis of rating
      errors.

PMID- 15565541
TI  - ["Vocationally Focused Interventions in Psychosomatic and Medical Rehabilitation:
      Research Findings, Practice, and Perspectives"--11th Conference of the Bavarian
      Rehab Sciences Research Network, RFB on May 7/8, 2004 in Prien].

PMID- 15565542
TI  - [Some remarks on the 20th World Congress of Rehabilitation International held
      June 2004 in Oslo, Norway].

PMID- 15565543
TI  - [Current developments and adverse trends in vocational rehabilitation of people
      with disability or at risk of being disabled--position of the committee on
      "Occupational and Work Disabled People" of the German Society for Rehabilitation
      of the Disabled].

PMID- 15565544
TI  - [Scientific results in paediatric oncology and haematology].

PMID- 15565545
TI  - mRNA Metabolism and hereditary disorders: a tale of surveillance and escape.
AB  - The exploration of the molecular origin of hereditary diseases focused on genes
      and proteins for many years. Recently, mRNA has gained increasing attention. Most
      human genes contain introns and a considerable proportion of transcripts are not
      only alternatively spliced but also regulated posttranscriptionally in manifold
      ways. mRNA processing as well as a complex network of interactions between the
      steps of gene expression and associated quality control mechanisms are guided by
      a multitude of regulative mRNA sequence elements. Therefore it is not surprising
      that mutations of such elements can cause or modify human disease. The purpose of
      this review is the illustration of principles of physiological and dysregulated
      mRNA metabolism as well as a survey of new analytical tools and therapeutic
      approaches.

PMID- 15565546
TI  - Identification of various exon combinations of the ews/fli1 translocation: an
      optimized RT-PCR method for paraffin embedded tissue -- a report by the CWS-study
      group.
AB  - BACKGROUND: Chromosomal translocations t(11;22) (q24;q12) are characteristic of
      about 80-90 % of Ewing's sarcoma family of tumors [bone and soft tissue Ewing's
      sarcoma and peripheral neuroectodermal tumors (PNET)]. They generate ews/fli1
      rearrangements showing great diversity in breakpoint exon combination. In about 5
      % of Ewing's tumors, ews is fused to the erg gene at 21q22. The various chimeric
      proteins encoded may function as aberrant oncogenic transcription factors. These
      specific translocations can be used for exact molecular diagnosis in these poorly
      differentiated small round-cell tumors. Moreover, the prognostic relevance of
      different translocational variants has been previously suggested. Furthermore,
      the sensitive molecular detection of minimal metastatic and residual disease and
      its clinical significance can be evaluated. To address these questions more
      definitively in the large number of patients registered in multicenter studies,
      it is often necessary to access archival paraffin-embedded tumor tissue if no
      fresh or frozen tumor material is available for analysis by RT (reverse
      transcription)-PCR. Specific problems arise from formalin-fixed and paraffin
      embedded tissue due to the degradation of RNA and insufficient extraction
      efficiency. Therefore, primer distance and product size are limited for
      successful PCR amplification. This conflicts with the requirement for
      identification of various possible exon combinations by PCR simultaneously using
      one single primer pair with larger distance. PATIENTS: We examined paraffin
      embedded soft part tumor tissue samples from 47 Ewing's tumor patients. Patients
      were treated according to either CWS (Cooperative Weichteilsarkomstudie, CWS-91
      or CWS-96) or Euro-E.W.I.N.G. 99 therapy protocols. METHOD: We established a
      novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs,
      selected according to the coding ews and fli1 nucleotide sequences (NCBI
      database), suitable for RT-PCR identification of variant ews/fli1 fusion
      transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue. For
      use in combination with ews -primer, an erg specific primer was selected to
      alternatively test for ews/erg fusion transcripts. As positive control for the
      integrity of isolated mRNA, we used the ubiquitously expressed gapdh transcript
      for RT-PCR amplification in each sample. RESULTS: In 31 cases (= 66 %) of 47
      paraffin samples of Ewing's tumors analysed, gapdh control indicated adequate
      quality of RNA. In 16 cases no gapdh control fragment was amplifiable,
      nevertheless in 2 of these 16 samples distinct ews fusion products could be
      detected. In 23 cases we identified ews fusion transcripts. Thereof in 65 % ews
      exon 7 being fused to fli1 exon 6 (fusion type I), in 22 % to fli1 exon 5 (fusion
      type II). In 4 % each ews exon 10 being juxtaposed to fli1 either exon 6 or exon
      5, respectively. An ews/erg fusion was detected in 4 % ( ews exon 7 fused to erg
      exon 6). In 10 samples, a gapdh fragment was amplified, but no ews/fli1 or - erg
      fusion transcript could be identified. The reference pathological review (I. L.,
      Kiel, Germany) disproved the primary histopathology in 5 cases. CONCLUSIONS:
      Using our different sets of exon specific primer pairs, it was possible to detect
      4 different breakpoints of ews/fli1 fusion transcripts and the ews/erg fusion by
      RT-PCR in RNA isolates from formalin-fixed, paraffin-embedded Ewing's tumor
      tissue. This method can be a very useful alternative in clinical situations (to
      ensure diagnosis and perform minimal metastatic and residual disease
      investigations) and in order to assess prognostic significance of translocation
      subtypes when no fresh tumor tissue is available.

PMID- 15565547
TI  - Differential diagnosis of suprasellar tumors in children.
AB  - In contrary to the adult age the most common suprasellar tumors in children are
      with decreasing frequency craniopharyngiomas, chiasmatic/hypothalamic low-grade
      gliomas, germinomas and lesions attributable to a Langerhans cell histiocytosis.
      For differential diagnostic purposes also the rare hypothalamic hamartoma and
      meningeal metastases in the infundibular recess of the third ventricle are
      included. The typical aspects of the various tumors on computed tomography (CT)
      and magnetic resonance imaging (MRI) together with important clinical differences
      are illustrated. On the basis of imaging results and clinical symptoms
      differential diagnosis between the various tumor entities should be feasible in
      many cases. Of course, only in strictly defined cases like typical
      chiasmatic/hypothalamic and optic pathway gliomas or bilocular germ cell tumors a
      histological confirmation is dispensable.

PMID- 15565548
TI  - Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy
      effectively defers radiotherapy within a comprehensive treatment strategy --
      report from the multicenter treatment study for children and adolescents with a
      low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and
      Hematology (GPOH).
AB  - BACKGROUND: Low grade gliomas arise in all CNS-locations and age groups,
      chiasmatic-hypothalamic tumors occur especially in young children. Early
      radiotherapy (RT) shall be deferred by chemotherapy (CT) within the concept of
      the HIT-LGG 1996 study, offering a comprehensive treatment strategy for all age
      groups. PATIENTS: 198 of 905 protocol patients (21.9 %) had a chiasmatic (34),
      chiasmatic-hypothalamic (144) or hypothalamic (20) primary tumor, median age at
      diagnosis 3.6 years (0.2-16.3 y.), 54 had neurofibromatosis (27.3 %), 108 female
      (54.5 %). 98 children had severe visual impairment as their first symptom. The
      initial neurosurgical intervention resulted in 5 complete, 26 subtotal, 45
      partial resections, 67 biopsies; 55 children had a diagnosis on the basis of
      neuroradiologic findings. Histology showed 132 pilocytic astrocytoma I degrees ,
      6 astrocytoma II degrees /nos and 2 DIGG/DIA I degrees (3 not known). RESULTS: 82
      children were treated at diagnosis, 68 upon clinical or radiological progression
      following observation times of 3.0 to 115.0 months. RT: 27 children received
      conventional (18) or interstitial (8) RT (1 not documented) at a median age of
      7.3 years; 7 tumors went into further progression. At a median observation time
      of 50.1 months 21 tumors are stable, 3 regressive (2 not evaluable, 1 death). CT:
      123 children received vincristin/carboplatin at a median age of 3.7 years.
      105/123 achieved CR/PR/SD. 44/123 tumors were progressive after median 22.5
      months, 37 with a chiasmatic-hypothalamic primary, 16/44 were irradiated. At a
      median observation time of 44.7 months 2 children are in complete remission, 92
      tumors are stable, 8 regressive, 9 progressive. 4 children died, 8 are not
      evaluable. At 60 months overall survival of the cohort is 0.93; PFS of the CT
      group is 0.61, the RT-free survival 0.83. Within the CT-group children with an
      age at diagnosis < 1 year and non-pilocytic histology are at increased risk for
      early progression. Causative factors cannot be defined, yet. CONCLUSION: Within
      the comprehensive treatment strategy for low grade glioma HIT-LGG 1996
      chemotherapy is effective to delay the need for early radiotherapy in chiasmatic
      hypothalamic glioma. More effective reduction of the risk for progression has to
      be sought for young children < 1 year.

PMID- 15565549
TI  - Prognosis and sequela in patients with childhood craniopharyngioma -- results of
      HIT-ENDO and update on KRANIOPHARYNGEOM 2000.
AB  - The overall survival rate of patients with craniopharyngioma, an embryogenic
      malformation, is high (0.92 +/- 0.03). However, there is considerable morbidity
      and impaired quality of life, even when the tumor can be completely resected. Aim
      of our study was to analyze risk factors for severe obesity (body mass index
      [BMI] > or = 7 SD) and the prognosis of severely obese survivors of childhood
      craniopharyngioma recruited in our cross-sectional study on 183 patients (HIT
      ENDO) and in the prospective study KRANIOPHARYNGEOM 2000. Severe obesity (BMI >
      or = 7 SD) was present in 16 % of patients and associated with higher tumor
      volume (p < 0.05), more frequent neurosurgical interventions (p < 0.05) and a
      higher rate of hypothalamic involvement (p < 0.001). Self-assessed functional
      capacity (FMH) was lower (p < 0.001) in severely obese survivors (FMH: median 33,
      range: 4-64) when compared with normal weight patients (FMH: 50; 1-95). Overall
      survival (20 years) was lower (p = 0.034) in patients with severe obesity in
      comparison to patients with moderate obesity and normal weight. Cardiovascular
      morbidity and mortality was high in severely obese patients. Between 10/01 and
      03/04 fifty-seven patients (27 female/30 male) were recruited in KRANIOPHARYNGEOM
      2000 (www.kraniopharyngeom.com). The impact of tumor localization (3.2 %
      intrasellar, 22.6 % suprasellar, 74.2 % combined intra/suprasellar; 51.6 %
      hypothalamic involvement) and treatment (26 complete resections, 22 partial
      resections followed by irradiation in one case; primary irradiation after biopsy
      in one case) on quality of life, functional capacity and prognosis will be
      evaluated longitudinally and prospectively.

PMID- 15565550
TI  - [Retrospective analysis of the clinical course of 12 children given the diagnosis
      essential thrombocythemia].
AB  - BACKGROUND: Essential Thrombocythemia (ET) is an acquired myeloproliferative
      disorder (MPD) characterized by excessive production of platelets. The disorder
      is usually affecting adults and is rarely diagnosed in children. PATIENTS AND
      METHODS: In this retrospective study we describe 12 children aged 5-16 years in
      whom ET was presumed. RESULTS: Median follow-up was 59 months (range 10-72). At
      diagnosis 7 patients had clinical symptoms (syncope, poor concentration, fatigue,
      abdominal pain and mild bleeding), 5 patients were diagnosed accidentally
      (operation, allergy, enuresis, pneumonia, routine examination). Median platelet
      count at diagnosis was 1 325 x 10 (9)/L (range 600-3 050). In 11 cases bone
      marrow morphology was consistent with ET, one patient had chronic idiopathic
      myelofibrosis. Cytogenetics were normal in all studied cases. Within 6 months
      after the initial presentation one patient who was diagnosed accidentally
      developed thrombosis, another patient had mild bleeding. 8 patients were treated
      with acetylsalicylic acid (in addition, 1 patient received hydroxyurea, 2
      patients received anagrelide). On last follow-up all patients were alive, none
      had developed leukemia. 5 patients experienced hematological remission. 2 of
      these children had not received any therapy. CONCLUSIONS: Many patients had
      symptoms attributable to ET. The clinical course is heterogeneous with complete
      normalization of platelets in the absence of cytoreductive therapy in some
      children. Due to the low incidence of ET in children indications for therapy are
      unclear and can only be deduced from findings obtained from studies in adults.

PMID- 15565551
TI  - Transplantation of haematopoietic stem cells derived from cord blood, bone marrow
      or peripheral blood: a single centre matched-pair analysis in a heterogeneous
      risk population.
AB  - BACKGROUND: Beside the transplantation of haematopoietic stem cells derived from
      bone marrow (BMT) and peripheral blood (PBSCT) in the absence of a well-matched
      donor, transplantation of cord blood (CBT) has been shown to be a valid
      alternative. To validate the efficacy of CBT in comparison to BMT and PBSCT we
      performed a single-centre based matched-pair analysis. PATIENTS AND METHODS:
      Between 1996 and 2003, 15 paediatric patients with non-malignant and malignant
      diseases of heterogenous risk underwent CBT. 198 paediatric patients undergoing
      BMT or PBSCT during the same time and at the same centre were available for
      selection as appropriate controls for matched-pair analysis. Matching criteria in
      descending hierarchy were disease, risk status, type of donor, age at HSCT,
      gender and year of transplantation. 47 % of CB grafts were < or = 4/6 HLA-matched
      whereas close to 90 % of grafts in the BMT and PBSCT cohorts were completely
      matched. RESULTS: Neutrophil engraftment was comparable in CB and BM recipients
      (p = 0.529) while engraftment following PBSCT occurs significantly earlier (p <
      0.01). Median time to neutrophil recovery was 20 (range: 13-36), 19 (14-28) and
      14 (9-24) days for the CBT, BMT and PBSCT cohort respectively. Of note contrary
      to the expectation, with regard to a reduced risk of Graft-versus-Host-Disease
      (GvHD) there was no clear advantage in the CBT cohort with a similar overall GvHD
      rate in all 3 groups. This observation can be attributed to the fact that in the
      CBT cohort the proportion of patients with an HLA-mismatched donor was higher
      than in the other cohorts. Rate of death of complications (DOC) was high in CB
      recipients (40 %), but not statistically different from BM (27 %) and PBSC
      recipients (13 %). In contrast to the CBT and BMT cohort with only 1 patient dead
      of disease (DOD), 4 PBSC recipients (31 %) died suffering from a relapse. 2-year
      event-free survival (EFS) in patients with malignant disease was 38.5 %, 69.2 %
      and 33.0 % for the CBT, BMT and PBSCT cohort respectively. 5-year overall
      survival (OS) was 53.3 % in the CBT, 66.4 % in the BMT and 50.9 % in the PBSCT
      cohort. There was no statistical difference between the cohorts transplanted with
      CB and BM or PBSC regarding EFS and OS (EFS: p = 0.24 and p = 0.72; OS: p = 0.53
      and p = 0.64). CONCLUSIONS: Transplantation of < or = 4/6 HLA-matched CB grafts
      seems to be associated with a higher risk of GvHD, graft rejection and lethal
      opportunistic infection. With an overall survival of 53 % in our 15 patients this
      analysis documents that even in high risk patients, CB may be a valid alternate
      HSC source in children who lack a well-matched donor. This is especially true, if
      a > 4/6 HLA-matched CB with > 2.0 x 10 (7) total nucleated cells/kg bodyweight is
      available. Thus, parallel to the search for a BM or PBSC donor, searching for an
      adequate CB unit should be initiated.

PMID- 15565552
TI  - Late effects after therapy of Hodgkin's disease: update 2003/04 on overwhelming
      post-splenectomy infections and secondary malignancies.
AB  - BACKGROUND: For a long time, a main focus of paediatric therapy studies for
      Hodgkin's disease (HD) has been on diminishing adverse late effects.
      Consequently, the long-term follow-up of patients after HD is very important. The
      HD late effects project of the GPOH, which evolved from 5 consecutive German
      Austrian DAL therapy studies, was aimed at establishing a basis for the further
      improvement of therapy concepts and of long-term surveillance. PATIENTS AND
      METHODS: The original cohort consisted of 1 245 study patients from 92 centres
      enrolled in the DAL studies HD-78 to HD-90 between 1978 and 1995. Initially,
      follow-up data were submitted by the participating study centres. When the
      majority of the patients had reached adult age and were no longer seen by the
      originally treating paediatric colleagues, we contacted them directly by mail
      every 2-3 years. At the time of analysis (March 2004) information from the
      preceding 6 years was available in 78.6 % of the patients alive. RESULTS: The
      median follow-up period of patients at the date of last information was 11.1
      years (max. 25.5 years), the median age was 23.7 years (max. 41.1 years). The
      present report is focused on three out of a wide range of problems evaluated,
      namely cause of death in 14 patients expired after 10-21 years' follow-up,
      overwhelming post-splenectomy infections (18 events, 11 fatal), and 46 secondary
      malignancies. The OS rate after 24 years is 87 % (SE 3 %) in the total group, 83
      % (SE 3 %) in 335 asplenic patients, and 93 % (SE 2 %) in 910 non- or partially
      splenectomised patients. We have initiated activities to improve the prophylactic
      measures against overwhelming infections in this risk group of asplenic patients.
      The cumulative incidences of secondary malignancies (SM) after 22 years is 11 %
      (SE 2 %) for all SM, 10 % (SE 2 %) for solid tumours, 0.8 % (SE 0.5 %) for NHL,
      and 0.6 % (SE 0.3 %) for leukaemias. The cumulative incidence of breast cancer in
      female patients at the age of 35 years is 4.0 % (SE 2 %). The effect of reducing
      the radiotherapy doses in the studies HD-87/HD-90 will become evident within the
      next years.

PMID- 15565553
TI  - Bone marrow oedema and aseptic osteonecrosis in children and adolescents with
      acute lymphoblastic leukaemia or non-Hodgkin-lymphoma treated with hyperbaric
      oxygen-therapy (HBO): an approach to cure? -- BME/AON and hyperbaric oxygen
      therapy as a treatment modality.
AB  - BACKGROUND: There is a striking need for additional therapies of bone marrow
      oedema (BME) and aseptic osteonecrosis (AON) in paediatric oncology patients.
      Hyperbaric oxygenation (HBO) therapy used in the treatment of osteoradionecrosis
      is demonstrated effectiveness. Aim of this retrospective analysis was to
      investigate whether HBO-therapy might lead to subjective as well as objective
      effects in the treatment of BME and/or AON in paediatric oncology patients with
      acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL). PATIENTS AND
      METHODS: Between 11/1988 and 01/2001 27/291 (9.3 %) patients with ALL or NHL were
      diagnosed with a BME and/or AON in the Clinic for Paediatric Oncology,
      Haematology, and Immunology at University of Dusseldorf. 19/27 patients were
      submitted to HBO-therapy. Patients received average 45 HBO-treatments per patient
      (min. 13, max. 80 treatments). The affected regions were re-evaluated with MRI
      for radiological extent of lesions every 3 months. Pain in its intensity and
      localisation was serially recorded during HBO-therapy as key symptom in 11 of 19
      patients. RESULTS: 27 patients (15 females, 12 males; mean age at diagnosis of
      malignancy 8.2 +/- 4.7 (SD) years, range 7 months to 16 years) presented with 138
      lesions. 133/138 lesions were localised in the lower extremities. At diagnosis of
      BME and/or AON, 78/133 lesions were shown in females and 55/133 lesions in male.
      Girls < 10 years predominantly presented BME (33 BME vs. 6 AON), girls aged > 10
      years predominantly offered AON (28 AON vs. 11 BME). BME was more often exhibited
      in boys < 10 years (34 BME vs. 10 AON) and rarely in boys > 10 years (4 BME vs. 6
      AON). 11 patients treated with HBO-therapy were serially evaluated for pain
      intensity throughout their HBO-therapy courses by visual analogue scale (VAS)
      assessment. During the first 15 treatment courses the HBO-therapy a clear-cut
      reduction of pain was observed. The mean pain score before the first HBO
      treatment unit was 2.4 +/- 2.7 (X +/- SD), decreased before the fifth to 1.6 +/-
      1.7 and prior to the 35 (th) and 40 (th) HBO treatment to 0. Girls < 10 years
      treated with HBO showed an increase of BME (31 --> 46) and declining AON numbers
      (6 --> 2). Girls > 10 years with and without HBO-therapy showed decrease of BME
      lesions (7 --> 4 vs. 4 --> 0), whereas AON increased in the HBO-treated group (28
      --> 29) as well as the non-treated group (0 --> 4). Males < 10 years showed an
      increase in BME lesion numbers despite HBO intervention (24 --> 26). The AON
      lesion numbers dropped in parallel (6 --> 3). Male patients not treated with HBO
      showed constant numbers of BME (11-->11) and a decreased numbers of AON (4 -->
      2). All differences are statistically not significant. CONCLUSIONS: Children and
      adolescents diagnosed with ALL or NHL have a risk for accruement of BME and/or
      AON irrespective of the age, with an almost exclusive involvement of the lower
      extremities. Lesions of pedal bones and ankle joints predominantly affect
      children < 10 years. Lesions of knee and hip joints predominantly affect children
      > 10 years. In children < 10 years of age we demonstrate declining AON numbers
      and conversion of AON to BME thereby implicating possible beneficial effect of
      HBO in such patients. HBO failed to show beneficial effect on BME whether by
      preventing new lesions or by improving existent lesions in children > 10 years.

PMID- 15565554
TI  - [Concepts of the Society of Paediatric Oncology and Haematology (GPOH) and the
      German Competence Network in Paediatric Oncology and Haematology for the quality
      controlled development in paediatric oncology].
AB  - For more than 30 years Paediatric Oncology has striven to achieve an optimum of
      care for children with cancer everywhere. The consistency of diagnostic
      procedures and treatment within successive therapy studies has yielded high cure
      rates. Meanwhile the focus has moved to placing the quality control of
      diagnostics and treatment into the hands of experts in the field, accommodating
      new requirements of the health care system. We report on the already realised and
      the future concepts and methods employed in improving the quality in institutions
      and studies with the support of the German Competence Network in Paediatric
      Oncology and Haematology (Kompetenznetz Padiatrische Onkologie und Hamatologie,
      KPOH). The issue of per-patient flat rate funding is raised, and structural
      requirements to be fulfilled by Centers of Paediatric Oncology are presented and
      discussed.

PMID- 15565555
TI  - Haemostatic alterations in colorectal cancer: perspectives for future treatment.
AB  - The role of the haemostatic system in colorectal cancer (CRC) is reviewed.
      Correlations between the activation of the haemostatic system and overall
      survival have been suggested. Experimental studies indicate that the haemostatic
      system plays a key role in growth, invasion and dissemination of tumour cells,
      and in tumour related angiogenesis. Additional activation by the surgical trauma
      and postoperative infections are discussed. Finally, anti-cancer modalities
      directed against regulation of the haemostatic system in CRC are considered.

PMID- 15565556
TI  - Detection of chromosome aberrations during prenatal genetic testing for single
      gene disorders.

PMID- 15565557
TI  - Masking of the clinical severity of severe haemophilia A in a patient with beta
      thalassemia major--its implications in prenatal diagnosis.

PMID- 15565558
TI  - Is there an optimal gestation for ultrasound examination of fetal nasal bone in
      the first trimester?

PMID- 15565559
TI  - Re: Verwaal VJ, van Tinteren H, Ruth SV, et al.: Toxicity of cytoreductive
      surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol 2004; 85:61
      67.

PMID- 15565560
TI  - Outcomes of dacryocystorhinostomy in patients with head and neck tumors.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcomes of
      dacryocystorhinostomy (DCR) in patients with head and neck tumors. METHODS: The
      clinical records of all 31 patients with head and neck tumors who underwent DCR
      for nasolacrimal duct blockage at The University of Texas M. D. Anderson Cancer
      Center between 1999 and 2003 were retrospectively reviewed. RESULTS: The tumor
      diagnoses were squamous cell carcinoma (n = 18), chondrosarcoma (n = 3),
      sinonasal carcinoma (n = 2), adenoid cystic carcinoma (n = 2), sinonasal
      papilloma (n = 2), esthesioneuroblastoma (n = 1); hemangiopericytoma (n = 1);
      ameloblastoma (n = 1), and osteosarcoma (n = 1). Twenty-eight patients had a
      maxillectomy or other sinus surgeries, 10 had radiotherapy, and 14 had
      chemotherapy and radiotherapy before DCR. All 31 patients (35 eyes) experienced
      improvement of epiphora after DCR, but five patients (six eyes) had recurrent
      nasolacrimal duct blockage develop during the study period. Two patients had mild
      wound infections; none had osteoradionecrosis. CONCLUSIONS: DCR alleviates
      nasolacrimal duct blockage in most patients with head and neck tumors and is not
      associated with unusual complications in this setting.

PMID- 15565561
TI  - Age-standardisation when target setting and auditing performance of Down syndrome
      screening programmes.
AB  - OBJECTIVE: To describe and illustrate a method of setting Down syndrome screening
      targets and auditing performance that allows for differences in the maternal age
      distribution. METHODS: A reference population was determined from a Gaussian
      model of maternal age. Target detection and false-positive rates were determined
      by standard statistical modelling techniques, except that the reference
      population rather than an observed population was used. Second-trimester marker
      parameters were obtained for Down syndrome from a large meta-analysis, and for
      unaffected pregnancies from the combined results of more than 600,000 screens in
      five centres. Audited detection and false-positive rates were the weighted
      average of the rates in five broad age groups corrected for viability bias.
      Weights were based on the age distributions in the reference population. RESULTS:
      Maternal age was found to approximate reasonably well to a Gaussian distribution
      with mean 27 years and standard deviation 5.5 years. Depending on marker
      combination, the target detection rates were 59 to 64% and false-positive rate
      4.2 to 5.4% for a 1 in 250 term cut-off; 65 to 68% and 6.1 to 7.3% for 1 in 270
      at mid-trimester. Among the five centres, the audited detection rate ranged from
      7% below target to 10% above target, with audited false-positive rates better
      than the target by 0.3 to 1.5%. CONCLUSION: Age-standardisation should help to
      improve screening quality by allowing for intrinsic differences between
      programmes, so that valid comparisons can be made.

PMID- 15565562
TI  - Placenta growth factor levels in second-trimester maternal serum in Down syndrome
      pregnancy and in the prediction of preeclampsia.
AB  - OBJECTIVES: To determine the levels of placenta growth factor (PlGF) in second
      trimester maternal serum samples from pregnancies affected with fetal Down
      syndrome and from those that developed preeclampsia and to assess the utility of
      PlGF as a screening tool for these conditions. METHODS: Residual second-trimester
      maternal serum samples were retrieved from freezer storage for 39 cases of Down
      syndrome and 44 pregnancies that later developed preeclampsia. Each case was
      matched to 5 control samples for gestational age at collection and duration of
      freezer storage. PlGF levels were measured in each sample by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: PlGF levels increased with gestational age
      between 15 and 20 gestational weeks. After adjusting for gestational-age effects,
      the median level of PlGF was 1.01 MoM in Down syndrome pregnancy and 0.74 MoM in
      pregnancies that developed preeclampsia, which were not significantly different
      from matched controls. The duration between sampling and onset of preeclampsia
      did not have an effect on the PlGF level. CONCLUSION: PlGF levels are not
      significantly altered in second-trimester maternal serum samples from cases of
      Down syndrome or in pregnancies that develop preeclampsia.

PMID- 15565563
TI  - Metastatic acinic cell carcinoma in a neurofibroma mistaken for carcinosarcoma.
AB  - BACKGROUND: Tumor-to-tumor metastasis is a rare, but well-recognized, entity most
      commonly involving metastatic carcinoma to a mesenchymal neoplasm. We report a
      case of acinic cell carcinoma of the parotid gland metastatic to a neurofibroma.
      METHODS AND RESULTS: A 55-year-old man with a history of a high-grade acinic cell
      carcinoma of the parotid was seen with a mass at the surgical site and metastatic
      foci in the scalp 10 months postoperatively. The resection specimen revealed a
      spindle cell lesion with metastatic foci of high-grade adenocarcinoma, initially
      diagnosed as a carcinosarcoma. The bland morphology and S-100-positive expression
      of the spindle cell lesion confirmed the diagnosis of neurofibroma. The high
      grade features of the carcinomatous foci and their similarity to the primary
      tumor confirmed the presence of a tumor-to-tumor metastasis. CONCLUSION: To our
      knowledge, this is the first reported case of acinic cell carcinoma metastatic to
      a neurofibroma, an important entity in the differential diagnosis of biphasic
      tumors of the head and neck.

PMID- 15565564
TI  - Initial response to percutaneous ablation predicts survival in patients with
      hepatocellular carcinoma.
AB  - Outcome predictors in patients with hepatocellular carcinoma (HCC) who are
      treated with percutaneous ablation are ill defined, and it is unknown if
      successful therapy is associated with improved survival. In our study, 282
      cirrhotic patients with early nonsurgical HCC were treated with percutaneous
      ablation during a 15-year period. Single tumors were seen in 244 patients, and 2
      to 3 nodules were seen in 38 patients. Initial complete response was achieved in
      192 patients and was independently related to the size of the main tumor (P =
      .015) and tumor stage (P = .0001) (< or =2 cm, 96%; 2.1-3 cm, 78%; >3 cm, 56%; 2
      3 nodules, 46%). At the end of follow-up, 80 patients presented sustained
      complete response. The 1-, 3-, and 5-year survival rates were 87%, 51%, and 27%,
      respectively. The independent predictors of survival were Child-Turcotte-Pugh
      class (P = .0001) and initial complete response (P = .006). Child-Turcotte-Pugh
      class A patients with initial complete response achieved 42% survival at 5 years;
      this figure increased to 63% in patients with tumors 2 cm or smaller. In
      conclusion, our results demonstrate that initial complete response to
      percutaneous ablation is associated with an improved survival in both Child
      Turcotte-Pugh class A and B patients with nonsurgical HCC. Accordingly, initial
      complete tumor necrosis should be considered a relevant therapeutic target
      irrespective of tumor size and liver function.

PMID- 15565565
TI  - New approaches in the treatment of myelofibrosis.
AB  - Myelofibrosis with myeloid metaplasia (MMM) is a chronic clonal neoangiogenesis
      disorder characterized by bone marrow fibrosis and neoangiogensis with
      extramedullary hematopoiesis. Identification of prognostic factors associated
      with MMM have not impacted the treatment of the disease, which continues to be
      palliative with the exception of allogeneic stem cell transplantation (SCT) for
      potential long-term disease-free survival in selected patients. Additional
      insights into the pathophysiology of MMM have resulted in the use of novel
      therapeutic strategies in the treatment of this disease. The rationale for the
      investigation of these agents in MMM and the status of clinical trials with
      various modalities such as angiogenesis inhibitors (e.g., thalidomide), tyrosine
      kinase inhibitors (e.g., imatinib mesylate), farnesyl transferase inhibitors
      (e.g., R115777), and other agents are reviewed, in addition to the potential
      roles of autologous and allogeneic SCT.

PMID- 15565566
TI  - Genetic polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1)
      and survival after chemotherapy for invasive breast carcinoma.
AB  - BACKGROUND: It has been suggested that genetic polymorphisms in certain
      glutathione-S-transferase (GST) genes reduce the effectiveness of detoxifying
      cytotoxins generated by chemotherapeutic agents, potentially resulting in
      enhanced clinical responses to chemotherapy. METHODS: The authors evaluated
      common polymorphisms in the GSTM1, GSTT1, and GSTP1 genes for associations with
      overall survival in 1034 patients with invasive breast carcinoma who were
      recruited into the Shanghai Breast Cancer Study between 1996 and 1998, treated
      with chemotherapy, and followed for a median of 5.3 years. RESULTS: After
      adjusting for age, tumor stage, and the use of radiotherapy and tamoxifen, women
      who were homozygous for the variant GSTP1 105Val allele had a 60% reduction in
      mortality risk compared with women who were homozygous for the Ile allele (hazard
      ratio, 0.4; 95% confidence interval, 0.2-0.8). No association was found with
      respect to any of the GSTM1 or GSTT1 genotypes. CONCLUSIONS: The results of the
      current study indicate a potential role for GSTP1 polymorphism in predicting the
      clinical outcomes of patients with breast carcinoma who are treated with
      chemotherapy.

PMID- 15565567
TI  - Implications of mediastinal uptake of 131I with regard to surgery in patients
      with differentiated thyroid carcinoma.
AB  - BACKGROUND: Findings of mediastinal uptake of 131I after surgical treatment for
      differentiated thyroid carcinoma (DTC) are common, especially in young patients.
      Given the frequency of false-positive findings, a protocol for diagnostic and
      therapeutic strategies would be useful. With the goal of accurately selecting
      management strategies, the authors analyzed their data and data found elsewhere
      in the literature for correlations with the incidence of mediastinal 131I uptake
      and with treatment for patients exhibiting such 131I uptake. METHODS: All
      patients with DTC who were treated between 1978 and 2000 at Groningen University
      Hospital (Groningen, The Netherlands) and who received adjuvant 131I ablation
      therapy were included in the current analysis, which involved retrospective
      review of all relevant data. RESULTS: Five hundred four patients with DTC
      initially underwent total thyroidectomy, with additional 131I ablation performed
      for 489 of these patients. In 48 of 489 patients (9.8%), 131I uptake was seen in
      the mediastinum on a posttreatment scan. Analysis of those 48 patients and of
      cases in the literature demonstrated that serum thyroglobulin levels, risk
      status, and the presence of thymus on radiologic images were important in the
      surgical decision-making process. CONCLUSIONS: Mediastinal uptake of 131I on
      posttreatment scans was found in approximately 10% of patients after total
      thyroidectomy for DTC. Based on the current data and the data presented in the
      literature, the authors developed a flow chart for determining appropriate
      treatment strategies, which included mediastinal dissection for high-risk
      patients and for patients with serum thyroglobulin levels > 10 ng/mL.

PMID- 15565568
TI  - Randomized trial of leuprorelin and flutamide in male patients with
      hepatocellular carcinoma treated with tamoxifen.
AB  - The growth of hepatocellular carcinoma (HCC) is thought to be dependent on
      androgens, as androgen receptors are present in most of these tumors. The aim of
      this multicenter trial was to assess the effect of antiandrogens in patients who
      have advanced HCC. Male patients with advanced HCC were randomized into 2 groups
      treated with (1) leuprorelin (3.75 mg/mo subcutaneously), flutamide (750 mg/d
      orally), and tamoxifen (30 mg/d orally) or (2) tamoxifen alone (30 mg/d orally)
      administered until death. Survival was the main end point (log-rank test). The
      required sample size was 375 patients (alpha, 5%; beta, 10%; 1-year survival, 45%
      in treated group and 30% in controls). Between February 1994 and January 1998,
      376 male patients (mean age, 66 years; treated group, n = 192; control group, n =
      184) were included. No baseline imbalance was found between the groups. At the
      reference date (January 1, 2003), 183 deaths (95.3%) were observed in the treated
      group and 177 deaths (96.2%) were observed in controls. Thirteen patients were
      lost to follow-up. Median survival time was estimated to be 135.5 days (95% CI,
      112-189) and 176 days (95% CI, 141-227) in treated and control groups,
      respectively (P = .21). Crude and adjusted relative risks of death in the treated
      group were estimated at 1.14 (95% CI, 0.93-1.40) and 1.08 (95% CI, 0.87-1.33; P =
      .48) respectively. Premature interruption of treatment was more frequent in the
      treated group (n = 45) than in controls (n = 22; P = .0045), mainly because of
      digestive side effects. In conclusion, no benefit in survival was found with
      antiandrogenic treatment in male patients with advanced HCC.

PMID- 15565569
TI  - Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a
      randomized placebo-controlled trial.
AB  - No effective medical therapy is currently available for primary sclerosing
      cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its
      effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like
      liver damage in animal models and reduces intestinal permeability. We recruited
      80 patients with PSC into a randomized placebo-controlled study to evaluate the
      effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression
      of PSC. Patients (41 UDCA/placebo and 39 UDCA/MTZ) were followed every third
      month. Assessment of liver function test, histological stage and grade, and
      cholangiography (via ERCP) at baseline showed no differences between the groups.
      After 36 months, serum aminotransferases gamma-glutamyltransferase, and alkaline
      phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly
      in the UDCA/MTZ group (-337 +/- 54 U/L, P < .05) compared with the UDCA/placebo
      group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (
      0.50 +/- 0.13, P < .01). The number of patients with improvement of stage (P <
      .05) and grade (P < .05) was higher in the combination group. ERCP findings
      showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and
      UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC
      improved serum ALP levels and New Mayo Risk Score, but no statistically
      significant effect on disease progression as assessed via liver histology or ERCP
      was seen. Long-term studies using a higher dose of UDCA combined with MTZ in
      larger patient populations are indicated.

PMID- 15565570
TI  - Prevalence of hepatic steatosis in an urban population in the United States:
      impact of ethnicity.
AB  - Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD),
      its pathogenesis and clinical significance remain poorly defined. In this study,
      we examined and compared the distribution of hepatic triglyceride content (HTGC)
      in 2,287 subjects from a multiethnic, population-based sample (32.1% white, 48.3%
      black, and 17.5% Hispanic) using proton magnetic resonance spectroscopy. HTGC
      varied over a wide range (0.0%-41.7%; median, 3.6%) in the population. Almost one
      third of the population had hepatic steatosis, and most subjects with hepatic
      steatosis had normal levels of serum alanine aminotransferase (79%). The
      frequency of hepatic steatosis varied significantly with ethnicity (45% in
      Hispanics; 33% in whites; 24% in blacks) and sex (42% in white men; 24% in white
      women). The higher prevalence of hepatic steatosis in Hispanics was due to the
      higher prevalence of obesity and insulin resistance in this ethnic group.
      However, the lower frequency of hepatic steatosis in blacks was not explained by
      ethnic differences in body mass index, insulin resistance, ethanol ingestion, or
      medication use. The prevalence of hepatic steatosis was greater in men than women
      among whites, but not in blacks or Hispanics. The ethnic differences in the
      frequency of hepatic steatosis in this study mirror those observed previously for
      NAFLD-related cirrhosis (Hispanics > whites > blacks). In conclusion, the
      significant ethnic and sex differences in the prevalence of hepatic steatosis
      documented in this study may have a profound impact on susceptibility to
      steatosis-related liver disease.

PMID- 15565571
TI  - Validation of a new prognostic staging system for hepatocellular carcinoma: the
      JIS score compared with the CLIP score.
AB  - The Japan Integrated Staging score (JIS score), which combines the Child-Turcotte
      Pugh classification and tumor-node-metastasis staging, has been proposed as a
      better prognostic staging system for hepatocellular carcinoma (HCC) than the
      Cancer of the Liver Italian Program (CLIP) scoring system. In this study,
      validation was performed among a larger patient population. A total of 4,525
      consecutive patients with HCC who had been diagnosed at five institutions were
      included. Stratification ability, prognostic predictive power, and
      reproducibility were analyzed and compared with results from the CLIP scoring
      system. Only 45% (1,951 of 4,525) of all patients were categorized as early stage
      HCC according to JIS score (0 or 1), whereas 63% (2,878 of 4,525) of the patients
      were categorized as having a CLIP score of 0 or 1. Significant differences in
      survival curves were not observed among CLIP scores 3 to 6. In contrast, survival
      curves showed significant differences among all the JIS scores. The same JIS
      scoring subgroups showed a similar prognosis, and good internal reproducibility
      was observed in each of the institutions. Multivariate analysis of the prognosis
      in all 4,525 patients proved the JIS score to be the best prognostic factor.
      Furthermore, the Akaike information criteria proved that the JIS scoring system
      was statistically a better model for predicting outcome than the CLIP scoring
      system. In conclusion, the stratification ability and prognostic predictive power
      of the JIS score were much better than that of the CLIP score and were simple to
      obtain and remember.

PMID- 15565572
TI  - Glutathione S-transferase and liver function in intrahepatic cholestasis of
      pregnancy and pruritus gravidarum.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease
      associated with poor maternal and fetal outcome. The diagnosis is based on
      pruritus with abnormal liver function in the absence of other pathological
      conditions. However, pruritus in pregnancy is common, and it may be the only
      presenting feature in ICP. No reliable test currently exists that can
      discriminate between those women destined to develop ICP and those with the
      benign condition of pruritus gravidarum (PG). The purpose of this prospective
      study was to investigate longitudinally the serum concentration of glutathione S
      transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to
      compare this with the temporal profile of conventional liver function markers in
      women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26).
      Blood was sampled on at least 3 separate occasions between 16 weeks of gestation
      and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in
      ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400%
      difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG
      (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period
      studied. Significant differences in the ICP compared with control and PG groups
      were also found for total bile acids, alanine aminotransferase, aspartate
      aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In
      conclusion, the measurement of GSTA provides a test of liver dysfunction that
      distinguishes women with ICP from those with PG. Additionally, on the basis of
      this study, reference ranges for biochemical markers of liver function require
      reevaluation in pregnancy.

PMID- 15565573
TI  - Phase II study of thalidomide in patients with unresectable hepatocellular
      carcinoma.
AB  - BACKGROUND: The hypervascular nature of hepatocellular carcinoma (HCC) is well
      characterized. Recent data have suggested that thalidomide possesses
      antiangiogenic and immunomodulatory activity. Therefore, the authors initiated a
      study to assess the efficacy and toxicity of thalidomide in patients with
      advanced HCC as primary and secondary endpoints, respectively. METHODS: Inclusion
      criteria were unresectable HCC with bidimentionally measurable disease, age > or
      = 18 years, Eastern Cooperative Oncology Group performance status < or = 2, and
      adequate organ function. Thalidomide was administered at a starting dose of 200
      mg per day in a 100-mg-per-week dose escalation regimen, up to the maximum
      tolerated dose or to 800 mg per day. Toxicity was monitored according to the
      National Cancer Institute Common Toxicity Criteria. RESULTS: Twenty-six of 27
      patients were eligible and assessable for toxicity and response. A median daily
      dose of 300 mg was achieved. One patient experienced near-complete recovery of
      alpha-fetoprotein levels and a partial radiographic response on computed
      tomography. Two patients had stable disease during the 16-week study period. The
      median duration of progression-free survival was 42 days. The overall median
      survival was 123 days. Fatigue and somnolence were the most common side effects,
      occurring in 81% and 62% of patients, respectively. No Grade 4 hematologic
      toxicity was observed. Three patients experienced Grade 4 hepatic toxicity
      (namely, hyperbilirubinemia). CONCLUSIONS: With gradual dose escalation,
      thalidomide was tolerated in most patients with advanced HCC. However, treatment
      with thalidomide alone was associated with only a modest response in the
      treatment of HCC.

PMID- 15565574
TI  - Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem
      glioma in children: results of a multiinstitutional study (SJHG-98).
AB  - BACKGROUND: The role of chemotherapy in the treatment of children with newly
      diagnosed diffuse brainstem glioma is uncertain. In the current study, the
      authors tested the efficacy of temozolomide treatment after radiotherapy (RT) in
      this setting. METHODS: Patients ages 3-21 years were eligible for the current
      multiinstitutional study. An optional window therapy regimen consisting of 2
      cycles of intravenous irinotecan (10 doses of 20 mg/m2 per day separated by 2
      days of rest per cycle) was delivered over 6 weeks and was followed by
      conventionally fractionated RT. The 5-day schedule of temozolomide (200 mg/m2 per
      day) was initiated 4 weeks after RT and was continued for a total of 6 cycles.
      The pharmacokinetics of temozolomide and its active metabolite, 5-(3
      methyltriazen-1-yl)imidazole-4-carboxamide (MTIC), were analyzed during Cycles 1
      and 3. RESULTS: Thirty-three patients (median age at diagnosis, 6.4 years) were
      enrolled. Of the 16 patients who received window therapy, 6 had irinotecan
      treatment discontinued due to clinical progression (n=5) or toxicity (n=1); the
      remaining 10 experienced disease stabilization after 2 cycles. All patients
      completed RT (median dose, 55.8 gray). Twenty-nine patients received a combined
      total of 125 cycles of temozolomide. Grade 3/4 neutropenia and thrombocytopenia
      occurred in 33% and 29% of all temozolomide cycles, respectively. In
      approximately one-third of the cycles, dose reduction was required due to
      myelosuppression. No correlation was demonstrated between temozolomide/MTIC
      exposure and myelosuppression at the conclusion of Cycle 1. All patients died of
      disease progression (median survival, 12 months). The estimated 1-year survival
      rate was 48% (standard error, 8%). CONCLUSIONS: The administration of
      temozolomide after RT did not alter the poor prognosis associated with newly
      diagnosed diffuse brainstem glioma in children.

PMID- 15565575
TI  - Solving the dilemma of the immunohistochemical and other methods used for scoring
      estrogen receptor and progesterone receptor in patients with invasive breast
      carcinoma.
AB  - BACKGROUND: The authors attempted to resolve the dilemma posed by the lack of
      unanimity concerning the optimal immunohistochemical (IHC) method for determining
      and scoring estrogen receptor (ER) and progesterone receptor (PR). METHODS:
      Sections for IHC were prepared from paraffin embedded tumor samples from 402
      patients with lymph node positive breast carcinoma who had biochemical receptor
      values (obtained with the dextran-coated charcoal [DCC] method) and who were
      enrolled in a prospective, randomized trial (National Surgical Adjuvant Breast
      and Bowel Project protocol B-09). IHC receptors were scored independently by two
      observers according to percent, intensity, and any-or-none algorithms. Results
      from these evaluations and from two computer-assisted evaluations, DCC, and
      common pathologic characteristics were analyzed for optimum splits for positive
      reactions in univariate and multivariate analyses using a tree-structured model.
      Concordance, sensitivity, and specificity were determined between the DCC method
      and all other methods. RESULTS: Interobserver agreement and concordance between
      the DCC method and the other methods and among the methods were high. Univariate
      analyses revealed that a positive ER score obtained with all methods was related
      significantly to overall survival (OS) at 5 years and at 10 years. Results
      related to PR scores and disease-free survival and recurrence-free survival were
      less consistent. In multivariate analysis, it also was found that all methods for
      scoring ER predicted a better prognosis for OS in patients with an unfavorable
      lymph node status at 5 years and 10 years. Patients in a favorable lymph node
      status group were discriminated further by nuclear grade. CONCLUSIONS: All IHC
      methods for scoring ER appeared valid as prognostic indicators of OS in patients
      with positive lymph nodes. The any-or-none IHC method, by virtue of its
      simplicity, represents an appropriate choice for practical use.

PMID- 15565576
TI  - Selective complexation of N-alkylpyridinium salts: binding of NAD+ in water.
AB  - A new class of receptor molecules is presented that is highly selective for N
      alkylpyridinium ions and electron-poor aromatics. Its key feature is the
      combination of a well-preorganized molecular clip with an electron-rich inner
      cavity and strategically placed, flanking bis-phosphonate monoester anions. This
      shape and arrangement of binding sites attracts predominantly flat electron-poor
      aromatics in water, binds them mainly by pi-cation, pi-pi, CH-pi, and hydrophobic
      interactions, and leads to their highly efficient desolvation. NAD(+) and NADP,
      the important cofactors of many redox enzymes, are recognized by the new receptor
      molecule, which embraces the catalytically active nicotinamide site and the
      adenine unit. Even nucleosides such as adenosine are likewise drawn into the
      clip's cavity. Complex formation and structures were examined by one- and two
      dimensional NMR spectroscopy, Job plot analyses, and isothermal titration
      microcalorimetric (ITC) measurements, as well as quantum chemical calculations of
      (1)H NMR shifts. The new receptor molecule is a promising tool for controlling
      enzymatic oxidation processes and for DNA chemistry.

PMID- 15565577
TI  - Lewis adducts of the side-on end-on dinitrogen-bridged complex [{(NPN)Ta}2(mu
      H)2(mu-eta 1:eta 2-N2)] with AlMe3, GaMe3, and B(C6F5)3: synthesis, structure,
      and spectroscopic properties.
AB  - Reaction of the side-on end-on dinitrogen complex [{(NPN)Ta}(2)(mu-H)(2)(mu
      eta(1):eta(2)-N(2))] (1; in which NPN=(PhNSiMe(2)CH(2))(2)PPh), with the Lewis
      acids XR(3) results in the adducts [{(NPN)Ta}(2)(mu-H)(2)(mu-eta(1):eta(2)
      NNXR(3))], XR(3)=GaMe(3) (2), AlMe(3) (3), and B(C(6)F(5))(3) (4). The solid
      state molecular structures of 2, 3, and 4 demonstrate that the N-N bond length
      increases relative to those found in 1 by 0.036, 0.043, and 0.073 A,
      respectively. In solution complexes 2-4 are fluxional as evidenced by variable
      temperature (1)H NMR spectroscopy. The (15)N{(1)H} NMR spectra of 2-4 are
      reported; furthermore, their vibrational properties and electronic structures are
      evaluated. The vibrational structures are found to be closely related to that of
      the parent complex 1. Detailed spectroscopic analysis on 2-4 leads to the
      identification of the theoretically expected six normal modes of the Ta(2)N(2)
      core. On the basis of experimental frequencies and the QCB-NCA procedure, the
      force constants are determined. Importantly, the N-N force constant decreases
      from 2.430 mdyn A(-1) in 1 to 1.876 (2), 1.729 (3), and 1.515 mdyn A(-1) (4), in
      line with the sequence of N-N bond lengths determined crystallographically. DFT
      calculations on a generic model of the Lewis acid adducts 2-4 reveal that the
      major donor interaction between the terminal nitrogen atom and the Lewis acid is
      mediated by a sigma/pi hybrid molecular orbital of N(2), corresponding to a sigma
      bond. Charge analysis performed for the adducts indicates that the negative
      charge on the terminal nitrogen atom of the dinitrogen ligand increases with
      respect to 1. The lengthening of the N-N bond observed for the Lewis adducts is
      therefore explained by the fact that charge donation from the complex fragment
      into the pi* orbitals of dinitrogen is increased, while electron density from the
      N-N bonding orbitals p(sigma) and pi(h) is withdrawn due to the sigma interaction
      with the Lewis acid.

PMID- 15565578
TI  - Acid zeolites as alcohol racemization catalysts: screening and application in
      biphasic dynamic kinetic resolution.
AB  - Acid zeolites were screened as heterogeneous catalysts for racemization of
      benzylic alcohols. The most promising zeolites appeared to be H-Beta zeolites,
      for which the optimal reaction conditions were studied in further detail. The
      zeolite performance was compared to that of homogeneous acids and acid resins
      under similar reaction conditions. In a second part of the research, H-Beta
      zeolites were applied in dynamic kinetic resolution (DKR) of 1-phenylethanol,
      which was conducted by means of a two-phase approach and which resulted in yields
      smoothly crossing the 50% border up to 90%, with an enantiomeric excess of >99%.
      To explore the applicability of this biphasic methodology, several other
      substrates were examined in the standard racemization reaction and in the
      biphasic dynamic kinetic resolution.

PMID- 15565579
TI  - Molecular-mechanical switch-based solid-state electrochromic devices.

PMID- 15565580
TI  - Recent perspectives in the role of chemotherapy in the management of advanced
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Recent advances in the treatment of nasopharyngeal carcinoma (NPC)
      have transpired into better treatment outcomes for patients with locoregionally
      advanced NPC, and have broadened the chemotherapeutic options for patients with
      metastatic disease. METHODS: Data for this review were identified through
      searches of articles published in PubMed, MEDLINE, and abstracts from selected
      conference proceedings up to 2004. RESULTS: The results of two meta-analyses and
      at least six randomized trials supported a survival benefit with the use of
      concurrent chemotherapy (e.g., platinum, tegafur-uracil [UFT)] and standard
      fractionated radiotherapy (with or without adjuvant chemotherapy) in the
      management of patients with locoregionally advanced NPC (nonmetastatic Stage
      III/IV disease, according to the staging system of the International Union
      Against Cancer). For those patients with metastatic NPC, platinum-based doublets
      using newer agents such as gemcitabine and the taxanes are reported to be better
      tolerated and can yield response rates comparable to those obtained with older,
      multidrug regimens. CONCLUSIONS: The current study reviewed the latest literature
      and pertinent issues concerning the role of chemotherapy in the treatment of
      patients with metastatic and locoregionally advanced NPC.

PMID- 15565581
TI  - Statistical discrimination in the presence of selection effects.
AB  - Discrimination between diseases is a complex task. Cases may present
      contradictory information and diseases can present with unusual or atypical
      symptoms. In many diagnostic problems the recorded diagnosis is either a true
      diagnosis, based on hard evidence, or a working diagnosis, not necessarily
      equivalent to the true underlying disease with an associated level of
      uncertainty. This problem is often confounded since the type of diagnosis given
      may be subjected to selection effects. Much medical data is categorical in
      nature, hence existing techniques for identifying selection effects are
      inappropriate. This paper provides a method of obtaining a single parameter
      modelling, the probability of giving a true diagnosis dependent on the nature of
      the true disease, thereby offering a simple measure for the presence of selection
      effects. When the size of the data is limited identifiability problems exist with
      calculating this parameter, however this paper shows how a sensitivity analysis
      based on the profile likelihood can be used to identify the presence of selection
      effects even in this difficult situation.

PMID- 15565582
TI  - YAP4 gene expression is induced in response to several forms of stress in
      Saccharomyces cerevisiae.
AB  - Exposure of Saccharomyces cerevisiae to several environmental insults, including
      conditions of oxidative, heavy metal, metalloid and heat stress, induces the
      expression of the YAP4 gene, previously shown to play a role in the response to
      hyperosmotic stress. Expression analyses in several mutant strains under pro
      oxidant conditions have determined that YAP4 is regulated by the transactivators
      Yap1p and Msn2p. Mutation of either the Yap1p-response element (YRE), located at 
      517 bp from the ATG, or the most proximal stress response element (STRE) at -430
      bp, is shown to strongly compromise YAP4 gene expression under these conditions.
      Furthermore, these two mutations in combination lead to a severe depletion of
      detectable mRNA levels, indicating interplay between the transcription factors
      Yap1p and Msn2p in the regulation of YAP4 transcription. Transcriptional
      activation of this gene reflects a concomitant increase in Yap4p protein levels
      that appear phosphorylated upon stress and negatively regulated by protein kinase
      A. Yap4p amino acid residues Ser89, Ser196 and Thr241 are shown to be required
      for protein phosphorylation and/or protein stability.

PMID- 15565583
TI  - Expression and secretion of a prokaryotic protein streptokinase without
      glycosylation and degradation in Schizosaccharomyces pombe.
AB  - Streptokinase (SK) is an important thrombolytic protein that is secreted by
      pathogenic strains of Streptococcus. Expression of streptokinase has been so far
      attempted in Pichia pastoris, Escherichia coli and Bacillus subtilis and shown to
      yield protein that was either highly glycosylated or degraded. Since the fission
      yeast, Schizosaccharomyces pombe, shares several molecular characteristics with
      higher eukaryotes, we decided to express the streptokinase gene in this yeast. A
      chimeric gene comprising the signal sequence of the Plus pheromone of Sz. pombe
      fused in-frame with the mature streptokinase from Streptococcus sp. was
      constructed and inserted into the expression vector containing the thiamine
      regulated promoter. We obtained a high level of expression of streptokinase
      comparable to that in E. coli and P. pastoris, with 50-100% processing of the
      signal sequence and secretion of the mature streptokinase into the periplasmic
      fraction. The mature enzyme co-migrates with the authentic mature SK in SDS gels,
      lacks any major modification and is functional. Importantly, a higher level of
      expression under stationary phase conditions and improved extractability of the
      mature and undegraded streptokinase was achieved in a novel mutant of Sz. pombe
      defective for a potent extracellular protease activity. We suggest that the
      unique vector/strain system developed here could be advantageous for large-scale
      production of prokaryotic proteins without significant modification or
      degradation in Sz. pombe.

PMID- 15565584
TI  - GUD1 (YDL238c) encodes Saccharomyces cerevisiae guanine deaminase, an enzyme
      expressed during post-diauxic growth.
AB  - Purine salvage is a complex pathway allowing a correct balance between adenylic
      and guanylic derivatives. In this paper, we show that GUD1 (YDL238c) encodes
      guanine deaminase, a catabolic enzyme producing xanthine and ammonia from
      guanine. Importantly, Gud1p activity was higher during post-diauxic growth,
      suggesting that a decrease of the guanylic nucleotide pool could be required when
      cells shift from proliferation to quiescence.

PMID- 15565585
TI  - Prenatal diagnosis of deletion of chromosome 6p presenting with hydrops fetalis.
AB  - OBJECTIVE: To report the first known case of 6p deletion presenting in utero with
      hydrops fetalis and multiple anomalies in the second trimester of pregnancy.
      METHODS: A thirty-year-old woman (gravida 3 para 1 abortion 1) was referred to
      our hospital at 18 weeks of gestation because of suspicion of fetal anomaly on
      routine ultrasound examination. A detailed anomaly scan revealed a single viable
      fetus with marked skin edema, marked ascites, pleural effusion, hydronephrosis of
      left kidney, absence of right kidney, cardiac anomaly and oligohydramnios. The
      fetal face was not visible due to the fetal position. Fetal karyotyping revealed
      46,XX,del(6)(p21.3). The couple opted to terminate the pregnancy. RESULTS: A
      hydropic female fetus was aborted and the autopsy revealed hydrops fetalis with
      bilateral cleft lips, hydronephrosis of left kidney, absence of right kidney,
      spleen, and thymus gland, truncus arteriosus, and single umbilical artery. Cord
      blood and tissue culture confirmed that the fetus had deletion of chromosome 6p.
      CONCLUSION: Deletion of short arm of chromosome 6 can result in hydrops fetalis
      in early pregnancy.

PMID- 15565586
TI  - Prenatal diagnostic procedures used in pregnancies with congenital malformations
      in 14 regions of Europe.
AB  - OBJECTIVE: To investigate outcomes of ultrasound investigations (US) and invasive
      diagnostic procedures in cases of congenital malformations (CM), and to compare
      the use of invasive prenatal test techniques (amniocentesis (AC) versus chorionic
      villus sampling (CVS)) among European populations. DESIGN: Analysis of data from
      population-based registries of CM. SUBJECTS: 25 400 cases of CM recorded by 14
      EUROCAT registries covering a total population of 1,013,352 births 1995-99.
      RESULTS: US were performed in 91% of cases, and positively detected CM in 35% of
      cases. AC was performed in 24% of the cases and CVS in 3% of cases. Thirty-eight
      percent of invasive tests gave positive results. Fifty-two percent of cases with
      maternal age > or = 35 years had an invasive test performed compared to 20% of
      cases with younger mothers. Considerable variation was found between registries
      in the uptake rate of invasive tests in cases with older maternal age and on the
      use of invasive tests with only four regions employing CVS techniques in at least
      a third of the cases having invasive tests. For chromosomal anomalies US gave
      positive results in 46% of cases with maternal age < 35 years with US performed
      and in 36% of cases with maternal age > or = 35 years with US performed.
      CONCLUSION: Prenatal US was performed in 91% of all pregnancies with CM but the
      test was only positive in a third of the cases. There was large regional
      variation in the uptake rate of invasive tests with maternal age of 35 years or
      more. For every CVS carried out there were nine AC tests. US is an important tool
      in the prenatal diagnosis of chromosomal anomalies in Europe.

PMID- 15565587
TI  - Two colons-two cancers: paradigm shift and clinical implications.
AB  - Embryological and physiological data suggest that proximal (in relation to the
      splenic flexure) and distal parts of the colon represent distinct anatomical and
      functional entities. Since 1990, molecular biologists have identified two
      distinct pathways, microsatellite instability (MSI) and chromosomal instability
      (CIN), which are involved in the pathogenesis of colon cancer (CC). Thus, a new
      paradigm has emerged with the discovery that CC is a heterogeneous disease;
      furthermore recent data have demonstrated that these two distinct pathways in
      colorectal carcinogenesis are characterized by a different clinical outcome. The
      implications for the clinicians are twofold; (1) tumors originating from the
      proximal colon have a better prognosis due to a high percentage of MSI-positive
      lesions; and (2) location of the neoplasm in reference to the splenic flexure
      should be documented before group stratification in ongoing trials of adjuvant
      chemotherapy for CC. In the future, clinical decision-making regarding adjuvant
      chemotherapy might be stratified according to the MSI status of cancers located
      proximally to the splenic flexure.

PMID- 15565588
TI  - Ultrasound (US) guided central venous catheterization of internal jugular vein on
      over 65-year-old patients versus blind technique.
AB  - BACKGROUND AND OBJECTIVES: Performing a central venous catheterization (CVC) on
      older patients for long-term central intravenous therapy could be a very
      important procedure. It could be associated with a high incidence of related
      complications, especially on over 65-year-old, high risk, selected patients.
      METHODS: The authors analyzed the results of 72 central venous CVC of internal
      jugular vein performed on over 65-year-old patients with ultrasound (US) guide
      from January 1998 to April 2003. RESULTS: The average performing time was 4 min,
      with 98.7% of success, 0% of major complications, and 4.1% of minor complications
      (one mild vagal hypotension and two catheter dislocation). CONCLUSIONS: The US
      guided technique is a safer procedure especially in older patients; it affords an
      easier and more rapid cannulation of a central vein, drastically reducing major
      and minor complications.

PMID- 15565589
TI  - Prenatal diagnosis of de novo pure partial monosomy 4p (4p15.1-->pter) in a
      growth-restricted fetus with a Greek warrior helmet face and unilateral facial
      cleft on three-dimensional ultrasound.

PMID- 15565590
TI  - Quantitative analysis of cellular fetal hemoglobin gamma chain messenger RNA (HbF
      gamma mRNA) in maternal peripheral blood.
AB  - OBJECTIVE: Fetal cells cross the feto-maternal barrier and circulate in maternal
      peripheral blood; thus, this study aimed to show the relationship between
      clinical evidence in pregnancy and qualitative feto-maternal barrier changes.
      METHODS: The expression of fetal hemoglobin gamma chain messenger RNA (HbF-gamma
      mRNA) was measured by quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) in maternal peripheral blood. RESULTS: HbF-gamma mRNA was
      detected in all pregnant women after 5 weeks of gestation. In normal pregnancy,
      there were two peaks at 10 and 40 weeks, and a significant increase 4 weeks prior
      to the onset of labor. In intrauterine growth restriction (IUGR), preterm
      delivery and placenta previa, the HbF-gamma mRNA expression was significantly
      higher than in normal pregnancies. CONCLUSION: The expression of HbF-gamma mRNA
      relative to that of beta-actin mRNA is thought to reflect the real-time leakage
      of fetal cells into maternal blood.

PMID- 15565591
TI  - Adjuvant hepatic arterial infusion after curative resection of colorectal liver
      metastases using removable intra-arterial catheters with shape-memory alloy.
AB  - BACKGROUND AND OBJECTIVES: Although there are some reports that adjuvant hepatic
      arterial infusion (HAI) chemotherapy reduces the hepatic recurrence following
      curative resection of colorectal liver metastases, problems of indwelling
      catheters after chemotherapy cessation remains unsolved. The usefulness of
      adjuvant HAI was investigated using a removable port-catheter system. METHODS:
      Spiral catheterstrade mark were attempted to be placed in 17 patients who
      underwent curative hepatectomy. The catheter contains a special shape-memory
      alloy at its tip, which allows stable fixation to the vascular wall without
      coiling so the catheter can be removed if necessary. 5-fluorouracil (5-FU) in
      total dose of 12 g was intra-arterially administered. RESULTS: W spiral
      catheterstrade mark were successfully placed in the hepatic artery by
      percutaneous approach in 82% of the patients. All patients underwent scheduled
      chemotherapy without serious adverse events. Reservoir-catheter system was
      removed easily and uneventfully after discontinuation of the chemotherapy. 3D-CT
      angiography revealed that the hepatic artery was well preserved with short-term
      chemotherapy. Postoperative hepatic recurrence was observed only in 18% of the
      patients with the median follow-up time of 19.9 months. CONCLUSIONS: Prophylactic
      5-FU HAI using W spiral cathetertrade mark and subsequent catheter extirpation is
      a promising strategy following curative resection of colorectal liver metastases.

PMID- 15565592
TI  - Hepatic arterial catheterization combining interventional radiological and
      laparotomic approaches.
AB  - BACKGROUND AND OBJECTIVES: This report describes a modified method of implanting
      a catheter-port system for hepatic arterial infusion chemotherapy (HAIC) that
      combines interventional radiological (IVR) and laparotomic approaches. METHODS
      AND RESULTS: In patients, scheduled for HAIC and laparotomic surgery, we now
      employ a modified method of implanting the catheter-port system. In our method,
      an IVR approach is used to implant the catheter-port, and arterial occlusions are
      primarily carried out using a laparotomic approach. Following celiac and superior
      mesenteric arteriographies, a tapered microcatheter with a side hole is inserted
      by a catheter exchange method. The catheter tip is advanced far into the
      gastroepiploic artery via the gastroduodenal artery (GDA). The side hole is
      located at the orifice of the proper hepatic artery, and its location is
      confirmed by injection of contrast media. The microcatheter is connected to the
      port, and the port is buried in the subcutaneous pocket. During the laparotomy
      stage, the GDA lumen and the catheter lumen are clipped, and the right gastric
      artery (RGA) and all small branches supplying the stomach, duodenum, and pancreas
      are ligated. Among the 13 patients successfully implanted with a port-catheter
      system using our combined approach, no patients had hepatic artery occlusion or
      occlusion of the catheter system. CONCLUSIONS: Initial results from a study of a
      new method of implanting a microcatheter-port system in the hepatic artery using
      combined IVR and laparotomic approaches suggest that this method may enable
      operators to avoid complicated selective coiling and may lower the incidence of
      hepatic artery occlusion in patients receiving long-term HAIC.

PMID- 15565593
TI  - A case of pure partial duplication 3q in a fetus due to a maternally inherited
      der(5)ins(5;3)(q33.1;q26.2q27) delineated by FISH.

PMID- 15565594
TI  - The prenatal scan pitfall for the diagnosis of renal mass: case report.

PMID- 15565595
TI  - Simultaneous repair of abdominal aortic aneurysm and resection of unexpected,
      associated abdominal malignancies.
AB  - BACKGROUND AND OBJECTIVES: The management of unexpected intra-abdominal
      malignancy, discovered at laparotomy for elective treatment of an abdominal
      aortic aneurysm (AAA), is controversial. It is still unclear whether both
      conditions should be treated simultaneously or a staged approach is to be
      preferred. To contribute in improving treatment guidelines, we retrospectively
      reviewed the records of patients undergoing laparotomy for elective AAA repair.
      METHODS: From January 1994 to March 2003, 253 patients underwent elective, trans
      peritoneal repair of an AAA. In four patients (1.6%), an associated, unexpected
      neoplasm was detected at abdominal exploration, consisting of one renal, one
      gastric, one ileal carcinoid, and one ascending colon tumor. All of them were
      treated at the same operation, after aortic repair and careful isolation of the
      prosthetic graft. RESULTS: The whole series' operative mortality was 3.6%. None
      of the patients simultaneously treated for AAA and tumor resection died in the
      postoperative period. No graft-related infections were observed. Simultaneous
      treatment of AAA and tumor did not prolong significantly the mean length of stay
      in the hospital, compared to standard treatment of AAA alone. CONCLUSIONS: Except
      for malignancies of organs requiring major surgical resections, simultaneous AAA
      repair and resection of an associated, unexpected abdominal neoplasm can be
      safely performed, in most of the patients, sparing the need for a second
      procedure. Endovascular grafting of the AAA can be a valuable tool in simplifying
      simultaneous treatment, or in staging the procedures with a very short delay.

PMID- 15565596
TI  - Biological, histological, and clinical impact of preoperative IL-2 administration
      in radically operable gastric cancer patients.
AB  - BACKGROUND AND OBJECTIVES: Surgery induces lymphocytopenia and this decrease of
      host defenses, related to interleukin-2 (IL-2) endogenous imbalance during
      postoperative period could promote the proliferation of possible micrometastases
      and the implantation of surgically disseminated tumor cells. Moreover, tumor
      infiltrating lymphocytes (TILs), activated by endogenous IL-2 release, are linked
      to prognosis in cancer patients. The aim of this randomized study is to assess
      the biological (peripheral blood cells count, related to the grade of
      immunosuppression), histological (TILs), and clinical (overall and disease-free
      survival) impact of preoperative low doses administration of IL-2 in patients
      with radically operable gastric cancer. METHODS: This prospective study enrolled
      69 consecutive patients with histologically proven gastric adenocarcinoma who
      underwent radical surgery from October 1999 to December 2002 (M/F 39/30; mean age
      66; range 42-82) who underwent radical surgery from October 1999 to December
      2000. Patients were randomized to be treated with surgery alone as controls (35
      patients) or surgery plus preoperative treatment with recombinant human IL-2 (34
      patients). We considered the total lymphocyte count and lymphocyte subset (CD4,
      CD4/CD8) during the preoperative period, before IL-2 administration, and on the
      14th and 50th day, peritumoral stromal (fibrosis) reaction, neutrophils,
      lymphocytes, and eosinophils infiltration in tumor histology, and morbidity
      disease free and overall survival were evaluated. RESULTS: Two groups were well
      matched for type of surgery and extent of disease. All the patients underwent
      radical surgery plus D2 lymphadenectomy. At baseline, there were no significant
      differences in total lymphocyte and lymphocyte subsets between groups. The
      control group showed a significant decrease of total lymphocytes, CD4 cells, and
      CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. In
      the control group 65% of patients had a decrease of CD4 under 500 cells/mmc.
      Instead it has been observed in IL-2 group a significant increase over the
      control group values of total lymphocytes and CD4 cells (14th total lymphocytes
      and CD4: IL-2 vs. control P < 0.05). Moreover in this group only 15% patients had
      CD4 under 500 cells/mmc. This difference, in CD4 count, is significant even at
      the 50th postoperative day (P = 0.006). IL-2 group showed lower postoperative
      complications (2/34 vs. 11/35; P < 0.05), and higher lymphocyte/eosinophil
      infiltration into the tumor (P < 0.0002). Median follow-up was 26 months (range
      10-48) and median overall and disease-free survivals were longer, even if not
      significantly, in the IL-2 group than in the control arm (P = 0.07 and P = 0.06
      respectively). CONCLUSIONS: This randomized study would suggest that a
      preoperative immunotherapy with IL-2 is a well-tolerated treatment able to
      prevent surgery-induced lymphocytopenia. IL-2 seems to neutralize the
      immunosuppression induced by operation and so to stimulate the host reaction
      against tumor tissue (lymphocytes/eosinophils infiltration). Furthermore IL-2
      seems to have an impact on clinical course reducing morbidity of surgery and
      ameliorating overall and disease-free survival.

PMID- 15565597
TI  - Ultrasound diagnosis of fetal anomalies: an analysis of perinatal management of
      318 consecutive pregnancies in a multidisciplinary setting.
AB  - OBJECTIVES: The objectives of this study are to analyse the perinatal management
      decisions made in a multidisciplinary setting following the prenatal diagnosis of
      fetal anomalies and to evaluate to what extent, in clinical practice, decisions
      about obstetric management are attuned to those about neonatal management.
      METHODS: Data on perinatal management of 318 consecutive singleton pregnancies
      presented to a multidisciplinary perinatal team in a tertiary centre were
      collected retrospectively. RESULTS: The multidisciplinary perinatal team decided
      upon non-aggressive obstetric management in 20% of the cases and consented to
      termination of pregnancy in 10% of the cases. The multidisciplinary perinatal
      team decided upon neonatal management in 112(36%) of all fetuses. In 100(89%) of
      these fetuses, standard neonatal management, and in 12(11%), no neonatal life
      sustaining treatment was decided upon. Implementation of the decisions of the
      multidisciplinary perinatal team on the various management modalities ranged from
      88 to 100%. CONCLUSION: The multidisciplinary perinatal team worked well in
      making decisions about obstetric management. In 30% of the cases, this concerned
      end-of-life decisions. However, for the majority of cases, the perinatal team did
      not plan neonatal management before birth and thereby did not attune obstetric
      and neonatal management to each other. This probably reflects the different
      attitudes towards end-of-life decisions between obstetricians and neonatologists.
      However, to ensure a consistent perinatal management, a multidisciplinary
      perinatal team has to make prenatal decisions about both obstetric and neonatal
      management.

PMID- 15565598
TI  - Prenatal diagnosis of radial agenesis in trisomy 18 using three-dimensional
      ultrasound.

PMID- 15565599
TI  - Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases.
AB  - BACKGROUND AND OBJECTIVES: Parathyroid carcinoma (PC) is a rare disease;
      experience with its management is limited. The aim of this retrospective study
      was to evaluate a relatively large series of patients suffering from PC. METHODS:
      Since 1980, PC was diagnosed in the 4.7% of cases of primary hyperparathyroidism
      (HPT) (19 patients). Clinical and biochemical features, and surgical outcome were
      analyzed. RESULTS: In patients with PC, the mean serum calcium was 3.34 mmol/L;
      the tumor size 30.5 mm. Malignancy was never diagnosed preoperatively. Thirty-two
      operations were performed; six patients underwent repeated surgery. Recurrence of
      HPT was observed in 100% of patients. The median disease-free interval was 15
      months (range 2-74 months). Fifteen patients died because of the disease; median
      survival was 29 months (range 20-146 months). A significant correlation was found
      between late recurrences and prolonged survival; less advanced age and higher
      preoperative calcium levels predicted early recurrences. CONCLUSIONS:
      Preoperative diagnosis of PC is difficult. Preoperative severe hypercalcemia
      should alert the surgeon. En bloc resection of the PC and the adjacent structures
      is the treatment of choice. Unfortunately, recurrences are common and long-term
      survival rate is low.

PMID- 15565600
TI  - Preliminary report on surgical technique in hepatic parenchymal transection for
      liver tumors in the elderly: a lesson learned from living-related liver
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Availability of hi-tech surgical devices has
      elaborated the technique of parenchymal transection during hepatectomy from
      classic crushing clamp technique 1,2 to a combination of an ultrasonic dissection
      with special type of cautery 3,4. We have developed a new technique to resect
      hepatic parenchyma using an ultrasonic surgical aspirator in association with a
      monopolar floating ball. This combination has been utilized in 42 liver
      resections. METHODS: A retrospective analysis of perioperative mortality, length
      of hospitalization, and blood transfusion during surgery in two patient groups
      who underwent liver resection was carried out. We divided the patient population
      into Group A (42 patients), who underwent the new technique, and Group B (107
      patients), who experienced the crushing clamp technique. A second analysis was
      performed, where we divided the same patient population group in Group 1 with age
      less than 65, and Group 2 including patients older than 65 years. RESULTS: We
      found that the new technique reduced length of stay, procedure length, and use of
      perioperative blood. We determined that the two age groups performed similarly in
      comparison to LOS, length of procedure, blood use, and complications. CONCLUSION:
      This enforces the fact that the elderly can receive such surgical treatment
      without hesitation.

PMID- 15565601
TI  - IRS-2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes.
AB  - To assess the role of insulin action and inaction in the liver, immortalized
      hepatocyte cell lines have been generated from insulin receptor substrate (IRS)
      2(-/-) and wild-type mice. Using this model, we have recently demonstrated that
      the lack of IRS-2 in neonatal hepatocytes resulted in insulin resistance. In the
      current study, we show that immortalized neonatal hepatocytes undergo apoptosis
      on serum withdrawal, with caspase-3 activation and DNA laddering occurring
      earlier in the absence of IRS-2. Insulin rescued wild-type hepatocytes from serum
      withdrawal-induced caspase-3 activation and DNA fragmentation in a dose-dependent
      manner, but it failed to rescue hepatocytes lacking IRS-2. In IRS-2(-/-) cells,
      insulin failed to phosphorylate Bad. Furthermore, in these cells, insulin was
      unable to translocate Foxo1 from the nucleus to the cytosol. Adenoviral infection
      of wild-type cells with constitutively active Foxo1 (ADA) induced caspase-8 and
      caspase-3 activities, proapoptotic gene expression, DNA laddering and apoptosis.
      Dominant negative Foxo1 regulated the whole pathway in an opposite manner.
      Prolonged insulin treatment (24 hours) increased expression of antiapoptotic
      genes (Bcl-xL), downregulated proapoptotic genes (Bim and nuclear Foxo1), and
      decreased caspase-3 activity in wild-type hepatocytes but not in IRS-2(-/-)
      cells. Infection of IRS-2(-/-) hepatocytes with adenovirus encoding IRS-2
      reconstituted phosphatidylinositol 3-kinase (PI 3-kinase)/Akt/Foxo1 signaling,
      restored pro- and antiapoptotic gene expression, and decreased caspase-3 activity
      in response to insulin, thereby blocking apoptosis. In conclusion, IRS-2
      signaling is specifically required through PIP3 generation to mediate the
      survival effects of insulin. Epidermal growth factor, via PIP3/Akt/Foxo1
      phosphorylation, was able to rescue IRS-2(-/-) hepatocytes from serum withdrawal
      induced apoptosis, modulating pro- and anti-apoptotic gene expression and
      downregulating caspase-3 activity.

PMID- 15565602
TI  - Termination of pregnancy: attitudes and behavior of women in a traditional
      society.
AB  - OBJECTIVES: The Bedouin Arabs, a Muslim traditional ethnic minority in Israel,
      are faced with difficult choices when offered prenatal diagnosis as part of the
      universally provided prenatal care in Israel. This paper is to examine attitudes
      towards and practice of pregnancy termination, following an unfavorable prenatal
      diagnosis. METHODS: Semistructured interviews with 83 women were conducted to
      study attitudes. Data from the Soroka Medical Center, where all births in the
      area take place, were used to assess the rate of terminations of pregnancies
      following a diagnosis of a chromosomal anomaly. RESULTS: While divided on the
      question of termination, many women believed that a second medical opinion is
      needed, preferably from an Arab physician. The reasons for termination are both
      child- and mother-related. Opposing termination is based on both the suspicion
      that the diagnosis might be wrong and on religious reasons. Between 1995 and
      1999, 686 Bedouin women had undergone amniocentesis (2.4% of all pregnancies).
      Six of 11 pregnancies with the diagnosis of a trisomy were terminated (54.5%).
      All cases in which a trisomy was terminated were trisomy 21. CONCLUSIONS:
      Culturally acceptable prenatal diagnostic services for Muslim populations should
      be based on early testing, and should involve Muslim physicians and religious
      authorities.

PMID- 15565603
TI  - Viral kinetics during antiviral therapy in patients with chronic hepatitis C and
      persistently normal ALT levels.
AB  - The aim of the present study was to compare viral kinetics between patients with
      chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels
      and those with elevated ALT levels. Kinetic parameters were derived from
      nonlinear, least square fitting of serum hepatitis C virus RNA quantifications
      collected from patients with chronic hepatitis C and persistently normal (n = 20)
      and elevated (n = 19) ALT levels before and during treatment with 180 mug
      pegylated interferon alpha-2a once weekly plus daily ribavirin. Patients with
      chronic hepatitis C and persistently normal ALT levels showed a trend to lower
      pretreatment infected cell loss (delta) (P = .13) but no differences in efficacy
      of blocking virus production (epsilon) and infected cell loss during treatment
      (mdelta) compared with patients with elevated ALT levels. Differences were
      significant for epsilon (P = .02) and delta (P = .04) when applying updated
      "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for
      male and female patients, respectively). A significant reduction of the kinetic
      parameters epsilon, delta, and mdelta was observed in patients with elevated
      gamma-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT
      levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral
      kinetics are similar in patients with chronic hepatitis C and persistently normal
      ALT levels and those with elevated ALT levels. However, in patients with elevated
      GGT levels, a major association with reduced efficacy of blocking virus
      production and lower infected cell loss was observed. These data show that
      virological response in patients with chronic hepatitis C is less associated with
      baseline ALT than with GGT levels.

PMID- 15565604
TI  - AASLD single-topic research conference on hepatocellular carcinoma: Conference
      proceedings.

PMID- 15565605
TI  - Relationship between hepatic enzymes and insulin resistance syndrome markers in
      HIV with lipodystrophy.

PMID- 15565606
TI  - Landmarks in hepatology. Au Conntraire, professeur Pasteur!

PMID- 15565609
TI  - TIPS versus paracentesis for the treatment of refractory ascites.

PMID- 15565610
TI  - Chronic hepatitis C virus infection: does it really impact health-related quality
      of life? A study in rural Egypt.
AB  - Previous Western studies showed a consistent and marked reduction in health
      related quality of life (HRQOL) in patients chronically infected with hepatitis C
      virus (HCV). However, these studies were conducted on patients whose knowledge of
      their serological status may have affected their HRQOL. This HRQOL survey
      conducted in the Egyptian rural population provides a unique opportunity to
      clarify this issue among a population whose serological status is unknown. HRQOL
      was assessed by an Arabic translation of the Short-Form 12, and a visual analog
      scale of the relative severity of one's health status. HCV chronic infection was
      defined by positive tests for anti-HCV antibody and HCV-RNA. HRQOL was compared
      according to HCV chronic infection status in linear mixed models adjusted for
      potential confounding factors, such as age, sex, education, and health care
      related risk factors, and adjusted for interviewer as a random effect. One
      hundred forty-six Egyptians chronically infected with HCV had similar Short-Form
      12 and visual analog scale scores, compared with 1,140 uninfected controls from
      the same rural community. In individuals chronically infected with HCV, serum
      aminotransferase levels did not correlate with HRQOL. In conclusion, this study
      did not find a significant reduction of HRQOL in patients chronically infected
      with HCV compared with uninfected, contemporaneous controls. This may be
      explained in part by a lower morbidity amongst patients chronically infected with
      HCV in rural Egypt and a higher morbidity amongst uninfected controls as compared
      with those of Western studies, as well as a lack of awareness of hepatitis C
      serological status.

PMID- 15565612
TI  - Contrast medium-associated renal dysfunction in patients with cirrhosis.

PMID- 15565613
TI  - Epoetin alfa improves quality of life in anemic HCV-infected patients receiving
      combination therapy.
AB  - Anemia and decreased health-related quality of life (HRQL) are common in patients
      receiving combination therapy of interferon alfa (IFN) and ribavirin (RBV) for
      chronic hepatitis C virus (HCV) infection. In a randomized, prospective study
      evaluating the effectiveness of epoetin alfa in maintaining RBV dose, alleviating
      anemia, and improving HRQL in anemic (Hb < or = 12 g/dL) HCV-infected patients
      receiving combination therapy, patients receiving epoetin alfa had significant
      improvements in HRQL compared with placebo. In this study, 185 patients were
      randomized to 40,000 units of epoetin alfa subcutaneously weekly or placebo for
      an 8-week double-blind phase (DBP), followed by an 8-week open-label phase during
      which all patients received epoetin alfa. To further assess the impact of epoetin
      alfa on HRQL, post hoc analyses were conducted in the same patient population to
      compare the HRQL of these patients at randomization with norms of other
      populations, and to determine the critical relationship between hemoglobin (Hb)
      levels and HRQL. Mean HRQL scores of anemic HCV-infected patients receiving
      combination therapy at randomization were significantly lower than those of both
      the general population and patients who had other chronic conditions. Patients
      receiving epoetin alfa who had the greatest Hb increases from randomization to
      the end of the DBP also had the largest improvements in HRQL. Hb improvement was
      an independent predictor of HRQL improvement in these patients. In conclusion,
      epoetin alfa provided clinically significant HRQL improvement in HCV-infected
      patients receiving IFN/RBV therapy.

PMID- 15565615
TI  - Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant
      hepatitis B virus infection.
AB  - Adefovir dipivoxil was recently approved for the treatment of wild-type and
      lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil
      fumarate, a congender of adefovir that is used in the treatment of HIV infected
      patients, has recently been shown to also be effective in patients with
      lamivudine-resistant HBV infection. We therefore compared the two substances in a
      study of 53 patients defined by high HBV DNA (>6 log10 copies/mL) levels and
      genotypic evidence of lamivudine resistance. Thirty-five patients received
      tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks.
      Changes in HBV DNA levels were followed for the complete period of 48 weeks.
      Early viral kinetics were compared on matched subgroups of 5 patients each.
      Individually, all tenofovir-treated patients showed a strong and early
      suppression of HBV DNA within a few weeks whether they were coinfected with HIV
      or were without comorbidity. In contrast, considerable individual variations in
      HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of
      these patients had HBV DNA levels below 10(5) copies/mL in contrast to 100% of
      the tenofovir-treated patients (P = .001). No severe side effects were noticed in
      either group. No evidence of phenotypic viral resistance could be demonstrated in
      the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion,
      tenofovir may become an effective alternative for the treatment of patients with
      lamivudine-resistant HBV infection.

PMID- 15565616
TI  - Progression of liver fibrosis in women infected with hepatitis C: long-term
      benefit of estrogen exposure.
AB  - Female sex is a protective factor for the progression of fibrosis in patients
      with chronic hepatitis C virus (HCV) infection. Experimental data suggest that
      estrogens may have an antifibrotic effect. The objective of this study was to
      evaluate the influence of past pregnancies, oral contraceptives, menopause, and
      hormone replacement therapy (HRT) on liver fibrosis progression in HCV-infected
      women. Four hundred seventy-two HCV-infected women received a survey regarding
      prior pregnancies, menopause, and the use of oral contraceptives and HRT. The
      impact of these variables on liver fibrosis and its progression were evaluated
      using multivariate analyses considering all putative confounding factors. Two
      hundred one women completed the survey (43% response rate), 157 of whom had an
      estimated date of HCV infection (96 postmenopausal women, 96 women with previous
      pregnancies, and 105 women with past use of oral contraceptives). Through
      multivariate analyses, the estimated rate of fibrosis progression was higher in
      postmenopausal (P < .05) and nulliparous (P = .02) women and was associated with
      greater histological activity (P < .001). Prior use of oral contraceptives had no
      significant influence. Among postmenopausal women, the estimated rate of fibrosis
      progression (+/-SE) was lower in women who received HRT compared with untreated
      patients (0.099 +/- 0.016 vs. 0.133 +/- 0.006 METAVIR units/yr; P = .02) and was
      similar to that of premenopausal women (0.093 +/- 0.012 METAVIR units/yr; P value
      not significant). In conclusion, menopause appears to be associated with
      accelerated liver fibrosis progression in HCV-infected women, an effect that may
      be prevented by HRT. Pregnancies may have a beneficial impact on the long-term
      progression of liver fibrosis.

PMID- 15565627
TI  - Waning immunity to plasma-derived hepatitis B vaccine and the need for boosters
      15 years after neonatal vaccination.
AB  - Neonatal immunization with hepatitis B (HB) vaccine is highly effective; however,
      more needs to be learned about the duration of protection and indications for
      boosters. We measured antibody to HB core antigen (anti-HBc), HB surface antigen
      (HBsAg), and pre- and postbooster titers of HBsAg antibody (anti-HBs) 15 years
      after primary neonatal immunization with plasma-derived HB vaccines in 2 cohorts
      of 15-year-old children. Group A consisted of 78 children who were born to HB e
      antigen-positive HBsAg carrier mothers and had developed protective levels of
      anti-HBs antibodies (> or =10 mIU/mL) following HB immunization. Group B
      consisted of 113 apparently healthy children whose anti-HBs titers after
      vaccination were unknown. Anti-HBs was undetectable (antibody titer <10 mIU/mL)
      in 29.9% in group A and 62.4% in group B (P < .001). Anti-HBc was detected in
      33.3 % in group A and 4.4 % in group B (P < .001). After a single booster dose of
      HB vaccine, 2.7% in group A and 3.3% in group B remained anti-HBs-negative. A
      blunted serological response was noted in approximately 20% in both groups. One
      HBsAg carrier was detected in group A (1.3%) and 4 in group B (3.5%). Fifteen
      years after neonatal immunization with plasma-derived HB vaccine, a large
      proportion of children exhibited waning immunity. This poses the risk of
      breakthrough infection. A single booster augmented the serological response to
      the vaccine in most but not all subjects. In conclusion, our findings suggest
      that one or more booster immunizations are needed in seronegative subjects by at
      least 15 years following neonatal immunization with plasma-derived HB vaccine.

PMID- 15565628
TI  - Surgical treatment for gastric carcinoma in the elderly.
AB  - BACKGROUND AND OBJECTIVES: The incidence of gastric cancer is increasing in the
      elderly. The aim of this study is to evaluate the impact of advanced age (> or
      =80 years) on morbidity, mortality and late outcome after curative surgery for
      gastric cancer. METHODS: The cases of 30 octogenarians (Group A) with gastric
      cancer who underwent surgical treatment in our Institution from 1990 to 2003 were
      reviewed and compared to a simultaneous group of 228 younger patients (Group B).
      RESULTS: The rate of resective and curative procedures was not different in the
      two groups, although the American Society of Anaesthesiologists (ASA) risk was
      significantly higher in the elderly (P < 0.001) and the lymphatic dissection was
      less extended in group A. In the two groups, the curability was directly
      correlated to the cancer stage, but not affected by the ASA risk. The
      postoperative morbidity and mortality rates were similar in the two groups and
      were not related to the ASA risk. Considering the mortality for gastric cancer
      alone, the two groups showed a similar survival rate, only correlated to the
      cancer stage. CONCLUSIONS: In the elderly, an oncologically correct surgical
      procedure can safely be prosecuted with satisfactory immediate and late results.

PMID- 15565629
TI  - Is the chronologic age a contra-indication for surgical palliation of
      unresectable periampullary neoplasms?
AB  - METHODS: Early and late results of surgical palliation for unresectable
      periampullary neoplasms were evaluated in 24 patients older than 70 years and
      compared with the same results obtained from 33 younger patients. The two groups
      of patients were comparable, except for age. Biliary bypass associated to gastric
      bypass was the most common performed procedure. RESULTS: No significant
      differences in the results (morbidity, mortality, and outcome) were found in the
      two groups of patients. In addition, the results of palliative surgery in the
      elderly were compared with those obtained from a comparable group of 35 patients
      palliated with endoscopic stent insertion: surgical palliation resulted in better
      long-term results. CONCLUSIONS: This study provides evidence that the chronologic
      age is not a contra-indication for surgical palliation of periampullary neoplasms
      and that surgery provides a better quality of residual life.

PMID- 15565630
TI  - Prognostic significance of the age factor in the thyroid cancer: statistical
      analysis.
AB  - BACKGROUND AND OBJECTIVES: To determine whether thyroid carcinoma in elderly
      patients presents any peculiar characteristics, whether the greater biological
      aggressiveness of the neoplasm modifies the surgical treatment selected, and
      whether age greater than 70 years represents an independent prognostic factor.
      METHODS: Retrospective analysis of case histories from the Department of Surgery
      of "La Sapienza" University of Rome; 403 patients subjected to total
      thyroidectomy between 1993 and 1999, with a minimum follow-up period of 3 years
      subdivided into three groups: group I (patients aged between 20 and 50 years),
      group II (patients aged between 51 and 70 years) and group III (patients aged >70
      years). The surgical and postoperative treatment is uniform in all study groups.
      RESULTS: Age greater than 70 years entails a significant increase in mortality;
      the mortality rate in the three groups was found to be 3%, 9% and 54%,
      respectively. Prognosis is significantly worse in the elderly patients group
      (group III) than in group I (P < or = 0.001) and in group II (P < or = 0.001);
      group II mortality was significantly higher than that of group I (P = 0.005); in
      group III, the neoplasm displays features of greater biological aggressiveness
      (greater incidence of undifferentiated forms, presence of lymph nodes at
      diagnosis and vascular invasion, locally advanced forms, greater incidence of
      stage IV). CONCLUSIONS: Statistical analysis shows that the greater biological
      aggressiveness of the neoplasm in elderly patients worsens the prognosis,
      although an age exceeding 70 years itself represents an unfavourable prognostic
      factor; total thyroidectomy does not present any counter-indications in elderly
      patients.

PMID- 15565631
TI  - Fluoxetine increases extracellular levels of 3-methoxy-4-hydroxyphenylglycol in
      cultured COLO320 DM cells.
AB  - Fluoxetine (Prozac) is a serotonin reuptake inhibitor. It increases extracellular
      levels of serotonin and is used in relieving the depressive symptoms of cancer
      patients. It has been reported that the drug may enhance the growth of certain
      cancer cells. This study investigates whether fluoxetine enhances the growth of a
      human colon cancer cell line (COLO320 DM) and if it affects the extracellular
      levels of serotonin or its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) and
      other monoamines and metabolites at two cell densities. The extracellular levels
      of serotonin, 5-HIAA and other monoamines and metabolites were measured
      simultaneously by high performance liquid chromatography from cell-culture media
      after incubation of cells both with and without fluoxetine for 3 days. The
      viability of COLO320 DM cells was evaluated using 3-(4,5-cimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide (MTT). At low cell densities (1.25x10(5) cells
      ml-1), fluoxetine at 1-10 microM significantly increased the extracellular levels
      of serotonin (p<0.005), 5-HIAA (p<0.005), and 3-methoxy-4-hydroxyphenylglycol
      (MHPG; p<0.001) as compared to the controls. Fluoxetine at 10-100 microM
      significantly inhibited the growth of COLO320 DM (p<0.005). At high cell
      densities (2x10(6) cells ml-1), fluoxetine at 1-10 microM significantly increased
      the extracellular levels of MHPG (p<0.01), and at 10 microM it significantly
      increased the extracellular levels of 5-HIAA (p<0.05). Fluoxetine at 100 microM
      significantly inhibited the growth of the cells (p<0.0001). These results suggest
      that fluoxetine at 1 microM of effective concentration may increase the
      extracellular levels MHPG, in addition to serotonin and 5-HIAA levels, yet not
      inhibit the growth of COLO320 DM.

PMID- 15565632
TI  - Role of hepatic fibrin in idiosyncrasy-like liver injury from lipopolysaccharide
      ranitidine coexposure in rats.
AB  - Coadministration of nonhepatotoxic doses of the histamine 2-receptor antagonist
      ranitidine (RAN) and bacterial lipopolysaccharide (LPS) results in hepatocellular
      injury in rats, the onset of which occurs in 3 to 6 hours. This reaction
      resembles RAN idiosyncratic hepatotoxicity in humans. Early fibrin deposition
      occurs in livers of rats cotreated with LPS/RAN. Accordingly, we tested the
      hypothesis that the hemostatic system contributes to liver injury in LPS/RAN
      treated rats. Rats were given either LPS (44.4 x 10(6) EU/kg) or its vehicle,
      then RAN (30 mg/kg) or its vehicle 2 hours later. They were killed 2, 3, 6, 12,
      or 24 hours after RAN treatment, and liver injury was estimated from serum
      alanine aminotransferase activity. A modest elevation in serum hyaluronic acid,
      which was most pronounced in LPS/RAN-cotreated rats, suggested altered sinusoidal
      endothelial cell function. A decrease in plasma fibrinogen and increases in
      thrombin-antithrombin dimers and in serum concentration of plasminogen activator
      inhibitor-1 occurred before the onset of liver injury. Hepatic fibrin deposition
      was observed in livers from LPS/RAN-cotreated rats 3 and 6 hours after RAN. Liver
      injury was abolished by the anticoagulant heparin and was significantly
      attenuated by the fibrinolytic agent streptokinase. Hypoxia, one potential
      consequence of sinusoidal fibrin deposition, was observed in livers of LPS/RAN
      treated rats. In conclusion, the results suggest that the hemostatic system is
      activated after LPS/RAN cotreatment and that fibrin deposition in liver is
      important for the genesis of hepatic parenchymal cell injury in this model.

PMID- 15565633
TI  - The effects of alcohol on rat placenta.
AB  - In this study, daily food and water consumption and body weights, histopathology
      of placenta, tenascin (TN), type IV collagen and EGF and its receptor
      immunolocalization in the placenta of albino rats treated with two doses of
      alcohol (1 and 5 g kg(-1) day(-1)) were determined. Alcohol was administered in
      three different periods i.e. the whole 4 weeks before the pregnancy, during the
      pregnancy, and during the 4 weeks before the pregnancy plus pregnancy itself. The
      samples of placenta obtained from control and treated rats on days 10, 12, 14,
      16, 18, 20 and 21 of gestation were evaluated morphologically and fixed for
      histology and immunohistochemistry. Some differences in food and water
      consumption between the groups were determined. The placental weight, especially
      in the groups receiving 1 and 5 g kg(-1) day(-1) alcohol during the pregnancy,
      showed increases. The changes in placental histology such as increases in the
      number and the size of trophoblastic giant cells, cytoplasmic dissolution and
      nuclear polymorphism, degenerations in spongiotrophoblasts, hyperemia at the
      basal zone and labyrinth, hyperplasia at the labyrinth and irregular
      vascularization were seen particularly in the groups receiving alcohol during the
      pregnancy, and during the 4 weeks before the pregnancy plus pregnancy itself.
      Increases in the immunolocalization of TN and type IV collagen and decreases in
      the immunolocalization of EGF and EGFR in the placentas of alcohol-receiving rats
      were found. In conclusion, ethanol treatment during pregnancy in rats affected
      placentation and the immunolocalization of TN, type IV collagen, EGF and EGFR in
      the placentas.

PMID- 15565634
TI  - Protective role of vanadium on the early process of rat mammary carcinogenesis by
      influencing expression of metallothionein, GGT-positive foci and DNA
      fragmentation.
AB  - Vanadium, a dietary micronutrient, is now proving to be a promising anti-tumour
      agent. The present study was conducted to ascertain its anti-neoplastic potential
      against an experimental mammary carcinogenesis. Female Sprague-Dawley rats at 50
      days of age were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA; 0.5 mg
      per 100 g body weight) by a single tail vein injection in an oil emulsion.
      Vanadium (ammonium monovanadate) at a concentration of 0.5 p.p.m. was
      supplemented in the drinking water and given ad libitum to the experimental group
      immediately after the carcinogen treatment and it continued until the termination
      of the study (24 weeks for histological, immunological and biochemical
      observations and 35 weeks for morphological findings). It was found that vanadium
      treatment brought about substantial protection against DMBA-induced mammary
      carcinogenesis. This was evident from histological findings that showed
      substantial repair of hyperplastic lesions following supplementation of vanadium
      alone. There was a significant reduction in incidence (P<0.05), total number,
      multiplicity (P<0.01), size of palpable mammary tumours and delay in mean latency
      period of tumour appearance (P<0.001) following vanadium supplementation compared
      to the DMBA control. The immunohistochemical localization of metallothionein (a
      prognostic marker for breast cancer) showed reduced expression with vanadium
      treatment. Further, DNA fragmentation in the mammary tissue of the vanadium
      treated group indicated apoptosis. In this group, vanadium also caused a
      significant decrease in the number (P<0.002) and focal area (P<0.05) of gamma
      glutaminetranspeptidase-positive hepatic foci. The results clearly show the anti
      neoplastic potential of vanadium.

PMID- 15565635
TI  - Developmental regulation and cellular distribution of human cytosolic malate
      dehydrogenase (MDH1).
AB  - Human cyotsolic malate dehydrogenase (MDH1) is important in transporting NADH
      equivalents across the mitochondrial membrane, controlling tricarboxylic acid
      (TCA) cycle pool size and providing contractile function. Cellular localization
      studies indicate that MDH1 mRNA expression has a strong tissue-specific
      distribution, being expressed primarily in cardiac and skeletal muscle and in the
      brain, at intermediate levels in the spleen, kidney, intestine, liver, and testes
      and at low levels in lung and bone marrow. The observed MDH1 localizations
      reflect the role of NADH in the support of a variety of functions in different
      organs. These functions are primarily related to aerobic energy production for
      muscle contraction, neuronal signal transmission, absorption/resorption
      functions, collagen-supporting functions, phagocytosis of dead cells, and
      processes related to gas exchange and cell division. During neonatal development,
      MDH1 is expressed in human embryonic heart as early as the 3rd month and then is
      over-expressed from the 5th month until the birth. The expression of MDH1 is
      maintained in the adult heart but is not present in levels as high as in the
      fetus. Finally, over-expression of MDH1 is found in left ventricular cardiac
      muscle of dilated cardiomyopathy (DCM) patients when contrasted to the diseased
      non-DCM and normal heart muscle by in situ hybridization and Western blot. These
      observations are compatible with the activation of glucose oxidation in
      relatively hypoxic environments of fetal and hypertrophied myocardium.

PMID- 15565636
TI  - Very long chain fatty acids activate NADPH oxidase in human dermal fibroblasts.
AB  - Very long chain fatty acids (VLCFAs) are exclusively oxidized in peroxisomes and
      their levels are significantly increased in tissues of patients with peroxisomal
      disorders. Although the biochemical indicators of peroxisomal dysfunction, such
      as elevated VLCFAs, are well known, the mechanisms of pathogenesis of peroxisomal
      diseases are unclear. In this study we have examined the effect of VLCFAs on
      NADPH oxidase (NOX), a complex enzyme system responsible for the production of
      superoxide anions, in order to understand the oxidative stress-mediated
      mechanisms involved in pathology of peroxisomal disorders. Varying concentrations
      (2.5 to 10 microg ml(-1)) of VLCFAs, lignoceric acid and cerotic acid,
      significantly (p < 0.001) increased the enzymic activity of NOX in cultures of
      human dermal fibroblasts. VLCFAs did not affect the expression of gp91phox or
      p22phox whereas the mRNA and protein levels of p47phox were significantly (two or
      three-fold) increased following treatment of fibroblasts with lignoceric acid or
      cerotic acid. VLCFAs also caused a significant (p < 0.01) increase in lipid
      peroxidation in dermal fibroblasts which could be markedly reversed by treatment
      with apocyanin (10 mM) or superoxide dismutase (SOD, 25 U ml(-1)). With these
      results, we report for the first time that VLCFAs enhance NOX activity and
      superoxide anion-mediated lipid peroxidation in cultured dermal fibroblasts. This
      study proposes a mechanism that may be taking place in vivo during peroxisomal
      dysfunction and that leads to oxidative stress-mediated pathogenesis.

PMID- 15565637
TI  - Thalidomide for advanced hepatocellular carcinoma: is this a real alternative?

PMID- 15565638
TI  - Alcohol-mediated haemolysis in yeast.
AB  - Although yeast are generally non-haemolytic, we have found that addition of
      alcohol vapour confers haemolytic properties on many strains of yeast and other
      fungi. We have called this phenomenon 'microbial alcohol-conferred haemolysis'
      (MACH). MACH is species- and strain-specific: whereas all six Candida tropicalis
      strains tested were haemolytic in the presence of ethanol, none among 10 C.
      glabrata strains tested exhibited this phenomenon. Among 27 C. albicans strains
      and 11 Saccharomyces cerevisiae strains tested, ethanol-mediated haemolysis was
      observed in 11 and 4 strains, respectively. Haemolysis is also dependent on the
      alcohol moiety: n-butanol and n-pentanol could also confer haemolysis, whereas
      methanol and 2-propanol did not. Haemolysis was found to be dependent on initial
      oxidation of the alcohol. Reduced haemolysis was observed in specific alcohol
      dehydrogenase mutants of both Aspergillus nidulans and S. cerevisiae. MACH was
      not observed during anaerobic growth, and was reduced in the presence of
      pararosaniline, an aldehyde scavenger. Results suggest that initial oxidation of
      the alcohol to the corresponding aldehyde is an essential step in the observed
      phenomenon.

PMID- 15565639
TI  - Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) as a
      subjective measure of drug-induced parkinsonism and akathisia.
AB  - The Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) was
      examined for its usefulness as a subjective measure of drug-induced parkinsonism
      and akathisia. Eighty-three subjects were assessed using the LUNSERS, the Simpson
      Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), before and after
      a 6-week treatment with olanzapine. Significant correlations were found between
      the changes in scores of parkinsonism items of LUNSERS and SAS. The changes in
      scores of akathisia item (restlessness), extrapyramidal side effects (EPS)
      subscale and psychic side-effects subscale of LUNSERS were significantly
      correlated with those of the BARS. 'Shakiness', one item of the EPS subscale of
      LUNSERS, correctly classified between parkinsonism and non-parkinsonism groups
      with 81.0% accuracy. A combination of four items included in EPS and psychic side
      effect subscales of LUNSERS identified akathisia and non-akathisia groups with
      76.2% accuracy. These results suggest that the EPS and psychic side-effect
      subscales of LUNSERS may be useful in screening for drug-induced parkinsonism and
      akathisia.

PMID- 15565640
TI  - Cost-effectiveness of prenatal screening for thalassaemia in Hong Kong.
AB  - OBJECTIVES: To determine the cost effectiveness of a universal prenatal screening
      program for alpha- and beta-thalassaemia. METHODS: We retrospectively reviewed
      our program from 1998 to 2002, and calculated the direct and indirect costs of
      various components. RESULTS: 18,936 women were screened at our prenatal clinic
      and 153 couples were subsequently referred to our Prenatal Diagnostic Centre for
      counselling and further investigations. In addition, there were 238 tertiary
      referrals and 157 self-referrals. After investigations, 84 fetuses were at risk
      of beta-thalassaemia major/beta-E thalassaemia, 19 of them were affected and 18
      were aborted. The total expenditure on our program (HK 10.0 million dollars)
      would be less than the postnatal service costs (HK 40.4 million dollars) for
      18beta-thalassaemia major fetuses if they were born. Of 361 women at risk of
      carrying a homozygous alpha0-thalassaemia fetus, 311 (86.2%) opted for the
      indirect approach (using serial ultrasound examinations to exclude Hb Bart's
      disease), and 76 (24.5%) subsequently underwent an invasive test for a definitive
      diagnosis. The sensitivity and false positive rate of this indirect approach was
      100.0% and 2.9% respectively. CONCLUSION: It is cost effective to run a universal
      prenatal screening program in an area where both beta-thalassaemia and alpha
      thalassaemia are prevalent. The indirect approach can effectively avoid an
      invasive test in unaffected pregnancies.

PMID- 15565641
TI  - A laboratory yeast strain suitable for spirit production.
AB  - Yeast strains of the species Saccharomyces cerevisiae currently in use for the
      production of consumable alcohols such as beer, wine and spirits are genetically
      largely undefined. This prevents the use of standard genetic manipulations, such
      as crossings and tetrad analysis, for strain improvement. Furthermore, it
      complicates the application of the majority of modern methods developed in yeast
      molecular biology. Here we used two haploid laboratory strains with suitable
      auxotrophic markers for the construction of a genetically well defined,
      prototrophic diploid production strain. This strain was tested for its
      fermentative and sensory performances in comparison to commercially available
      yeasts. Three different fruit mashes (cherries, plums and pears) were fermented
      in a 90 kg scale. These were then subjected to distillation and used for the
      production of spirits with a final ethanol content of 40% (v/v). Fermentation
      parameters assayed included growth, sugar utilization, ethanol production and
      generation of volatile compounds, higher alcohols and glycerol. The spirits were
      also tested for their sensory performances and the data obtained statistically
      consolidated. Our results clearly demonstrate that this laboratory strain does
      not display any disadvantage compared with commercial yeasts in spirit production
      for any of the parameters tested, yet it offers the potential to apply both
      classical breeding and modern molecular genetic techniques for adjusting yeast
      physiology to special production schemes.

PMID- 15565642
TI  - p53 and DPC4 alterations in the bile of patients with pancreatic carcinoma.
AB  - INTRODUCTION: Pancreatic cancer is still predominantly diagnosed in advanced
      stages, and 85%-90% of patients are not eligible for surgery at diagnosis. This
      is mainly due to the great difficulty in detecting the tumour at an early stage
      and presently no satisfactory results have been obtained to overcome this
      problem. Studies on molecular genetic profile of pancreatic cancer may represent
      an important approach. This study was focused on the mutations of p53 and DPC4
      detectable in the bile of patients with histologically proven pancreatic cancers.
      MATERIALS AND PATIENTS: We analysed specimens of bile collected through
      percutaneous transhepatic biliary catheters, placed to treat malignant biliary
      obstruction in 25 patients with pancreatic adenocarcinoma. A percentage of
      mutation was obtained of 43 % for the microsatellite D17S945 (p53), 54% and 50 %
      for D18S46 and D18S474 (DPC4), respectively. The percentage of amplification was
      67%, 93,6%, and 80%. CONCLUSION: We consider the results encouraging enough to
      decide to enlarge the number of patients examined. The aim is to determine if a
      test for DPC4 and p53 mutations is eligible for introduction in clinical routine
      use. More sets of samples are required to satisfactorily answer this question.

PMID- 15565643
TI  - The biology of a prostate cancer metastasis suppressor protein: Raf kinase
      inhibitor protein.
AB  - Raf kinase inhibitor protein (RKIP) was originally identified as a protein that
      bound membrane phospholipids and was named phosphatidylethanolamine binding
      protein-2 (PEBP-2). RKIP was than identified as a protein that bound Raf and
      blocked its ability to phosphorylate MEK, thus earning its new name of RKIP.
      Subsequent to identification of its role in the Raf:MEK pathway, RKIP has been
      demonstrated to regulate several other signaling pathways including G-protein
      signaling and NF-kappaB signaling. Its involvement in several signaling pathways
      has engendered RKIP to contribute to several physiological processes including
      membrane biosynthesis, spermatogenesis, neural development, and apoptosis. RKIP
      is expressed in many tissues including brain, lung, and liver and thus,
      dysregulation of RKIP expression or function has potential to contribute to
      pathophysiology in these tissues. Loss of RKIP expression in prostate cancer
      cells confers a metastatic phenotype on them. Additionally, restoration of RKIP
      expression in a metastatic prostate cancer cell line does not effect primary
      tumor growth, but it does inhibit prostate cancer metastasis. These parameters
      identify RKIP as a metastasis suppressor gene. In this review, the biology and
      pathophysiology of RKIP is described.

PMID- 15565644
TI  - Prenatal diagnosis of DMD in a female foetus affected by Turner syndrome.
AB  - OBJECTIVES: We report on a prenatal diagnosis of DMD complicated by a 45,X
      karyotype that was revealed only in the chorionic villus long-term culture.
      METHODS: Cytogenetic investigations were performed on both short-term (STC) and
      long-term cultures (LTC) of the chorionic villus sample. Familial segregation was
      performed using a panel of intragenic polymorphic markers, and multiplex PCR was
      used to characterize exonic deletion. RESULTS: Investigations performed for sex
      determination after STC of the chorionic villus sample showed a normal karyotype
      46,XX, while the karyotype performed after LTC revealed a homogeneous monosomy X.
      Cytogenetic analysis performed on amniotic fluid cells showed 45,X/46,XX
      mosaicism. Familial segregation analysis for DMD showed loss of heterozygosity
      for the STR49 marker in the DNA of the proband, her mother and the foetus.
      Dystrophin gene analysis on the 45,X cells led to the identification of a
      deletion of exon 50. CONCLUSIONS: The report described a rare situation of
      monosomy X associated with a DMD genotype. The data confirmed the DMD carrier
      status of the proband and her mother and indicated that the foetus had a high
      risk to combine a Turner phenotype and DMD. This study illustrated the potential
      risk of using short-term culture of villi as the only source of biological
      material for prenatal diagnosis.

PMID- 15565645
TI  - Bax-induced cell death in Candida albicans.
AB  - Bax is a pro-apoptotic member of the Bcl-2 family of proteins involved in the
      regulation of genetically programmed cell death in mammalian cells. It has been
      shown that heterologous expression of Bax in several yeast species, such as
      Saccharomyces cerevisiae, Schizosaccharomyces pombe and Pichia pastoris, also
      induces cell death. In this study we investigated the effects of Bax expression
      in the pathogenic yeast Candida albicans. Cell death inducing expression of Bax
      required a synthetic BAX gene that was codon-optimized for expression in Candida
      albicans. Expression of this BAX gene resulted in growth inhibition and cell
      death. By fusing Bax with the yeast enhanced green fluorescent protein of
      Aequoria victoria, the cell death-inducing effect of Bax was increased due to
      reduced proteolytic degradation of Bax. Using this fusion protein we showed that,
      upon expression in C. albicans, Bax co-localizes with the mitochondria.
      Furthermore, we showed for the first time that expression of Bax in yeast causes
      the mitochondria, which are normally distributed throughout the cell, to cluster
      in the perinuclear region.

PMID- 15565646
TI  - Basic region of residues 228-231 of protein kinase CK1alpha is involved in its
      interaction with axin: binding to axin does not affect the kinase activity.
AB  - Protein kinase CK1, also known as casein kinase 1, participates in the
      phosphorylation of beta-catenin, which regulates the functioning of the Wnt
      signaling cascade involved in embryogenesis and carcinogenesis. beta-catenin
      phosphorylation occurs in a multiprotein complex assembled on the scaffold
      protein axin. The interaction of CK1alpha from Danio rerio with mouse-axin has
      been studied using a pull-down assay that uses fragments of axin fused to
      glutathione S transferase, which is bound to glutathione sepharose beads. The
      results indicate that the three lysines present in the basic region of residues
      228-231 of CK1alpha are necessary for the binding of CK1 to axin. Lysine 231 is
      particularly important in this interaction. In order to define the relevance of
      the axin-CK1alpha interaction, the effect of the presence of axin on the
      phosphorylating activity of CK1alpha was tested. It is also evident that the
      region of axin downstream of residues 503-562 is required for CK1alpha
      interaction. The binding of CK1alpha to axin fragment 292-681 does not facilitate
      the phosphorylation of beta-catenin despite the fact that this axin fragment can
      also bind beta-catenin. Binding of CK1alpha to axin is not required for the
      phosphorylation of axin itself and, likewise, axin does not affect the kinetic
      parameters of the CK1alpha towards casein or a specific peptide substrate.

PMID- 15565647
TI  - Survey of genetically engineered mouse models for prostate cancer: analyzing the
      molecular basis of prostate cancer development, progression, and metastasis.
AB  - Genetically engineered mouse models have been generated to study the molecular
      basis of prostate cancer (PCa) development, progression, and metastasis.
      Selection of a prostate-specific promoter, such as the probasin (PB) and prostate
      specific antigen (PSA) promoters, is critical for generating sufficient levels of
      transgene expression to elicit a phenotypic response. To date, target genes have
      included growth factors, cell cycle regulators, pro- and anti-apoptotic proteins,
      steroid hormone and growth factor receptors, oncogenes, tumor suppressors, and
      homeobox genes. The experimental approaches used to generate these mouse models
      include overexpression of the transgene, knock-out/knock-in of transgene
      expression and conditional regulation of expression using Cre/lox technology.
      This review summarizes the promoters, which have been utilized to create
      genetically engineered mouse models for PCa. Furthermore, the effects of gene
      disruption on promoting low- and high-grade intraepithelial neoplasia (LGPIN and
      HGPIN, respectively), locally invasive carcinoma and metastatic lesions will be
      discussed. To date, the PB-Cre4 x PTENloxp/loxp model appears to be the only
      model that represents the entire continuum of prostate adenocarcinoma
      development, tumor progression, and metastasis, although models that develop
      prostatic neuroendocrine (NE) cancer can be generated by disrupting one genetic
      event. Indeed, analysis of bigenic mouse models indicates that two genetic events
      are generally required for progression from HGPIN to locally invasive
      adenocarcinoma and that two to five genetic events can promote metastasis to
      distant sites. Studying the effects of genetic perturbation on PCa biology will
      increase our understanding of the disease process and potentially provide targets
      for developing novel therapeutic approaches.

PMID- 15565648
TI  - Improved prenatal detection of a fetal point mutation for achondroplasia by the
      use of size-fractionated circulatory DNA in maternal plasma--case report.
AB  - INTRODUCTION: The efficacious analysis of fetal loci involving point mutations
      from circulatory fetal DNA in maternal plasma is hindered by the preponderance of
      maternal DNA. It has recently been shown that the size difference between fetal
      and maternal DNA species can be used for the selective enrichment of circulatory
      fetal DNA in maternal plasma. We have now tested this approach for the detection
      of a fetal point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene
      that causes achondroplasia. METHODS: Circulatory DNA was extracted from maternal
      plasma and size-fractionated by agarose gel electrophoresis. The fraction with a
      size less than 300 bp was examined by a touchdown PCR assay specific for the
      FGFR3 gene, and the mutation was identified by SfcI restriction analysis. RESULT:
      Our analysis indicated that although the fetal mutation was discernible in the
      analysis of total plasma DNA, the result using size-fractionated DNA was much
      more evident. CONCLUSION: The enrichment of circulatory fetal DNA in maternal
      plasma by size-fractionation facilitates the detection of subtle feto-maternal
      genetic differences, such as those involving point mutations. This approach can
      easily be extended for the non-invasive prenatal determination of other fetal
      loci.

PMID- 15565649
TI  - SWI/SNF chromatin remodeling complex is obligatory for BMP2-induced, Runx2
      dependent skeletal gene expression that controls osteoblast differentiation.
AB  - Development of bone tissue requires maturation of osteoblasts from mesenchymal
      precursors. BMP2, a member of the TGFbeta superfamily, and the Runx2 (AML3/Cbfa1)
      transcription factor, a downstream BMP2 effector, are regulatory signals required
      for osteoblast differentiation. While Runx2 responsive osteogenic gene expression
      has been functionally linked to alterations in chromatin structure, the factors
      that govern this chromatin remodeling remain to be identified. Here, we address
      the role of the SWI/SNF chromatin remodeling enzymes in BMP2-induced, Runx2
      dependent development of the osteoblast phenotype. For these studies, we have
      examined calvarial cells from wild-type (WT) mice and mice that are homozygous
      for the Runx2 null allele, as well as the C2C12 model of BMP2-induced
      osteogenesis. By the analysis of microarray data, we find that several components
      of the SWI/SNF complex are regulated during BMP2-mediated osteoblast
      differentiation. Brg1 is an essential DNA dependent ATPase subunit of the SWI/SNF
      complex. Thus, functional studies were carried out using a fibroblast cell line
      that conditionally expresses a mutant Brg1 protein, which exerts a dominant
      negative effect on SWI/SNF function. Our findings demonstrate that SWI/SNF is
      required for BMP2-induced expression of alkaline phosphatase (APase), an early
      marker reflecting Runx2 control of osteoblast differentiation. In addition, Brg1
      is expressed in cells within the developing skeleton of the mouse embryo as well
      as in osteoblasts ex vivo. Taken together these results support the concept that
      BMP2-mediated osteogenesis requires Runx2, and demonstrates that initiation of
      BMP2-induced, Runx2-dependent skeletal gene expression requires SWI/SNF chromatin
      remodeling complexes.

PMID- 15565650
TI  - Vanadium induces apoptosis and modulates the expressions of metallothionein, Ki
      67 nuclear antigen, and p53 during 2-acetylaminofluorene-induced rat liver
      preneoplasia.
AB  - Our previous studies have shown that vanadium, a dietary micronutrient, has an
      inhibitory effect against experimentally induced rat hepatocarcinogenesis. In
      this study, we evaluated the role of vanadium on some potential protein
      expression markers of carcinogenesis, such as metallothionein (MT), an
      intracellular metal-binding protein linked with cell proliferation and apoptosis,
      Ki-67 nuclear antigen, and p53 tumor suppressor during 2-acetylaminofluorene (2
      AAF)-induced (0.05% in basal diet) rat liver preneoplasia. In a short-term
      regimen, supplementation of vanadium at a dose of 0.5 ppm effectively suppressed
      the formation of DNA 'comets' (29.55%; P < 0.02), thereby indicating its
      nongenotoxicity at this particular dose. Vanadium administration throughout the
      study reduced relative liver weight (RLW), nodular incidence (57.15%), total
      number, and multiplicity (48.45%) with restoration of hepatic zinc (Zn),
      magnesium (Mg), selenium (Se), copper (Cu), iron (Fe), and calcium (Ca) contents
      when compared to the carcinogen control. Moreover, treatment with vanadium
      significantly abated the expressions of MT and Ki-67, studied at four sequential
      time points. An increased immunopositivity of p53 protein (1.03 +/- 0.23%; P <
      0.02) was found in vanadium-treated rat liver with an elevated apoptotic-labeling
      index (AI; P < 0.001) as documented by TUNEL assay. Furthermore, a positive
      correlation between MT expression and Ki-67 labeling along with a strong negative
      correlation between MT immunoreactivity and AI (r = -0.9000, P = 0.0004 at week
      24) at various time intervals suggest that, vanadium-mediated suppression of MT
      and Ki-67 expressions may be associated with induction of apoptosis. The results
      thus provide evidence for the first time in support of the potential role of
      vanadium on induction of p53 and apoptosis with concurrent suppression of MT and
      Ki-67 in order to have an understanding, in part, of the chemopreventive
      mechanism of this trace element in limiting neoplastic transformation in a
      defined model of experimental rat hepatocarcinogenesis.

PMID- 15565651
TI  - Low-grade steatosis and major changes in portal flow as new prognostic factors in
      steroid-treated alcoholic hepatitis.
AB  - The aim of this study was to assess the prevalence and prognostic value of major
      alterations of portal flow in patients with steroid-treated alcoholic hepatitis.
      Fifty patients with severe, histologically proven alcoholic hepatitis were
      enrolled. Clinical data, liver test results, and hepatic Doppler ultrasound
      findings were collected at inclusion and at month 2. Patients were followed for 1
      year or until death. Major changes in portal flow were defined as reversed or
      alternating flow in the portal trunk and/or in intrahepatic portal branches.
      Changes in portal flow were observed in 24 (48.0%) of 50 and 17 (39.5%) of 43
      patients at inclusion and month 2, respectively. Univariate analysis showed that
      age older than 50 years, steatosis less than 20% on initial liver biopsy,
      presence of major changes in portal flow, Child-Turcotte-Pugh score higher than
      12, factor V level higher than 45%, and hepatofugal splenic blood flow were
      associated with a lower 1-year survival. Cox regression analysis showed that
      steatosis < 20% (relative hazard [RH] = 9.3, P = .0009) and major changes in
      portal flow (RH = 3.1, P = .04), were independently associated with poor
      survival. In conclusion, major changes in portal flow are frequent in patients
      with severe alcoholic hepatitis. Altered portal flow and steatosis < 20% are new
      prognostic factors in steroid-treated alcoholic hepatitis and must be taken into
      account in patient management.

PMID- 15565652
TI  - BH(4) (tetrahydrobiopterin)-dependent activation, but not the expression, of
      inducible NOS (nitric oxide synthase)-2 in proinflammatory cytokine-stimulated,
      cultured normal human astrocytes is mediated by MEK-ERK kinases.
AB  - Nitric oxide (NO) from astrocytes is one of the signalers used by the brain's
      extensive glial-neuronal-vascular network, but its excessive production by pro
      inflammatory cytokine-stimulated glial cells can be cytodestructive. Here, we
      show how three pro-inflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma)
      together stimulated the activation, but not the prior expression, of NOS-2
      protein via a mechanism involving MEK-ERKs protein kinases in astrocytes from
      adult human cerebral temporal cortex. The cytokines triggered a transient burst
      of p38 MAPK activity and the production of NOS-2 mRNA which were followed by
      bursts of MEK-ERK activities, synthesis of the NOS-2 co-factor
      tetrahydrobiopterin (BH(4)), a build-up of NOS-2 protein and from it active NOS-2
      enzyme. Selectively inhibiting MEK1/MEK2, but not the earlier burst of p38 MAPK
      activity, with a brief exposure to U0126 between 24 and 24.5 h after adding the
      cytokine triad affected neither NOS-2 expression nor NOS-2 protein accumulation
      but stopped BH(4) synthesis and the assembly of the NOS-2 protein into active NOS
      2 enzyme. The complete blockage of active NOS-2 production by the brief exposure
      to U0126 was bypassed by simply adding BH(4) to the culture medium. Therefore,
      this cytokine triad triggered two completely separable, tandem operating
      mechanisms in normal human astrocytes, the first being NOS-2 gene expression and
      accumulation of NOS-2 protein and the second being the synthesis of the BH(4)
      factor needed to dimerize the NOS-2 protein into active, NO-making NOS-2 enzyme.

PMID- 15565653
TI  - A serological testing algorithm for the diagnosis of primary CMV infection in
      pregnant women.
AB  - OBJECTIVES: Serological diagnosis of CMV primary infection is usually based on
      the detection of specific IgM antibody. However, as the presence of IgM antibody
      is not always correlated with primary infection, measurement of IgG avidity must
      be performed. The aim of our study was to evaluate the best procedure for
      serological diagnosis of CMV primary infection. In other words, is it better to
      first search for IgM antibody, and, if positive, then measure IgG avidity, or
      first measure IgG avidity without the detection of IgM antibody? MATERIALS: CMV
      IgM detection and CMV-IgG avidity measurement were performed on 310 IgG positive
      sera from pregnant women. RESULTS: CMV-IgM antibody was detected positive for 9
      of 310 sera. Using CMV-IgG avidity index (AI), dating of infection was difficult
      in 81/310 cases (26%), while it failed in only 3/310 cases using CMV-IgM plus CMV
      IgG AI. CONCLUSION: The diagnosis of primary CMV infection can be based on the
      detection of CMV-IgM antibody first and then on the measurement of CMV-IgG AI.

PMID- 15565654
TI  - Uptake of a prenatal screening test: the role of healthcare professionals'
      attitudes towards the test.
AB  - OBJECTIVE: To investigate the association between healthcare professionals'
      attitudes towards prenatal Down syndrome screening and screening uptake in the
      women who consult them. METHODS: The attitudes of 71 midwives and 18
      obstetricians towards Down syndrome screening and screening uptake in the women
      who consulted them were assessed at two UK hospitals where uptake rates of Down
      syndrome screening differed (26 vs 61%). RESULTS: Healthcare professionals based
      at the hospital with higher screening uptake had more positive attitudes towards
      Down syndrome screening than healthcare professionals based at the hospital with
      lower screening uptake (19 vs 17, p = 0.03). Pooling across hospitals,
      obstetricians had more positive attitudes than midwives (20 vs 17, p = 0.004). In
      a sub-group of women who discussed screening with one healthcare professional,
      there was no significant association between individual healthcare professionals'
      attitudes and screening uptake (Spearman correlation coefficient = 0.13, p =
      0.51). CONCLUSION: In this study powered to detect a correlation of 0.5 and over
      (i.e. a large effect), healthcare professionals' attitudes towards screening were
      unrelated to uptake of screening in the women consulting them. It remains to be
      determined if a smaller effect exists. The observed association between
      healthcare professionals' attitudes and uptake rates by hospitals raises the
      question of whether healthcare professionals' attitudes might influence systems
      of care, not just communication with pregnant women.

PMID- 15565655
TI  - Meconium peritonitis presenting as isolated massive fetal ascites.

PMID- 15565656
TI  - Prenatal diagnosis for arginase deficiency by second-trimester fetal erythrocyte
      arginase assay and first-trimester ARG1 mutation analysis.
AB  - Hyperargininemia is a progressive neurometabolic disorder caused by deficiency of
      hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. We
      diagnosed arginase deficiency in a three-year-old male child of first-cousin
      Palestinian Arab parents. Prenatal diagnosis of an unaffected fetus was achieved
      in the second trimester of a subsequent pregnancy by cordocentesis and analysis
      of arginase activity in fetal erythrocytes. ARG1 mutation analysis in the proband
      revealed homozygosity for a deletion of 10,753 bp extending from the first intron
      to beyond the poly (A) site of the gene. This is the first gross deletion in the
      ARG1 gene to be identified and the first mutation to be described in an arginase
      deficient patient of this ethnic origin. The identification of the ARG1 deletion
      in this family enabled first-trimester prenatal diagnosis in a subsequent
      pregnancy by multiplex PCR analysis performed on chorionic villous DNA.

PMID- 15565657
TI  - Biliverdin therapy protects rat livers from ischemia and reperfusion injury.
AB  - Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative
      stress and catalyzes the rate-limiting step in heme metabolism that produces
      biliverdin (BV). The role of BV and its potential use in preventing
      ischemia/reperfusion injury (IRI) had never been studied. This study was designed
      to explore putative cytoprotective functions of BV during hepatic IRI in rat
      liver models of ex vivo perfusion and orthotopic liver transplantation (OLT)
      after prolonged periods of cold ischemia. In an ex vivo hepatic IRI model,
      adjunctive BV improved portal venous blood flow, increased bile production, and
      decreased hepatocellular damage. These findings were correlated with amelioration
      of histological features of IRI, as assessed by Suzuki's criteria. Following cold
      ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in
      untreated controls to 90% to 100%. This effect correlated with improved liver
      function and preserved hepatic architecture. Additionally, BV adjuvant after OLT
      decreased endothelial expression of cellular adhesion molecules (P-selectin and
      intracellular adhesion molecule 1), and decreased the extent of infiltration by
      neutrophils and inflammatory macrophages. BV also inhibited expression of
      inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1beta,
      tumor necrosis factor alpha, and interleukin 6) in OLTs. Finally, BV therapy
      promoted an increased expression of antiapoptotic molecules independently of HO-1
      expression, consistent with BV being an important mediator through which HO-1
      prevents cell death. In conclusion, this study documents and dissects potent
      cytoprotective effects of BV in well-established rat models of hepatic IRI. Our
      results provide the rationale for a novel therapeutic approach using BV to
      maximize the function and thus the availability of donor organs.

PMID- 15565658
TI  - Prenatal ultrasound diagnosis of a case of Pfeiffer syndrome without cloverleaf
      skull and review of the literature.
AB  - Pfeiffer syndrome is characterized by bilateral coronal craniosynostosis, midface
      hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes.
      Originally, it was described in eight persons from three generations in a
      pedigree consistent with an autosomal dominant transmission. Since then, several
      reports have documented its high clinical and genetic heterogeneity. The
      condition is usually detected in the newborn period or later, and very few
      prenatal ultrasound diagnoses have been reported. We present a case of Pfeiffer
      syndrome prenatally diagnosed at 20 weeks' gestation, in which the sonographic
      features of craniosynostosis, hypertelorism associated with an extreme proptosis,
      and broad thumb led to the diagnosis, confirmed after termination of pregnancy by
      dysmorphological, pathological and radiological evaluation. DNA analysis of the
      fibroblast growth factor receptor 2 (FGFR2) showed a missense mutation consisting
      in a transversion G --> C at nucleotide 870. This led to a Trp290Cys amino acidic
      substitution. We discuss the relevant findings of our and previously published
      cases. Our report demonstrates that a careful sonographic examination can lead to
      an early prenatal diagnosis of Pfeiffer syndrome also in cases without cloverleaf
      skull.

PMID- 15565659
TI  - Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T
      cell apoptosis in mice.
AB  - In the injured liver, hepatic stellate cells (HSCs) secrete many different
      cytokines, recruit lymphocytes, and thus participate actively in the pathogenesis
      of liver disease. Little is known of the role of HSCs in immune responses. In
      this study, HSCs isolated from C57BL/10 (H2b) mice were found to express scant
      key surface molecules in the quiescent stage. Activated HSCs express major
      histocompatibility complex class I, costimulatory molecules, and produce a
      variety of cytokines. Stimulation by interferon gamma (IFN-gamma) or activated T
      cells enhanced expression of these molecules. Interestingly, addition of the
      activated (but not quiescent) HSCs suppressed thymidine uptake by T cells that
      were stimulated by alloantigens or by anti-CD3-mediated T-cell receptor ligation
      in a dose-dependent manner. High cytokine production by the T cells suggests that
      the inhibition was probably not a result of suppression of their activation. T
      cell division was also found to be normal in a CFSE dilution assay. The HSC
      induced T-cell hyporesponsiveness was associated with enhanced T-cell apoptosis.
      Activation of HSCs was associated with markedly enhanced expression of B7-H1.
      Blockade of B7-H1/PD-1 ligation significantly reduced HSC immunomodulatory
      activity, suggesting an important role of B7-H1. In conclusion, the bidirectional
      interactions between HSCs and immune cells may contribute to hepatic immune
      tolerance.

PMID- 15565660
TI  - Disruption of hepatic adipogenesis is associated with impaired liver regeneration
      in mice.
AB  - The liver responds to injury with regulated tissue regeneration. During early
      regeneration, the liver accumulates fat. Neither the mechanisms responsible for
      nor the functional significance of this transient steatosis have been determined.
      In this study, we examined patterns of gene expression associated with hepatic
      fat accumulation in regenerating liver and tested the hypothesis that disruption
      of hepatic fat accumulation would be associated with impaired hepatic
      regeneration. First, microarray-based gene expression analysis revealed that
      several genes typically induced during adipocyte differentiation were
      specifically upregulated in the regenerating liver prior to peak hepatocellular
      fat accumulation. These observations suggest that hepatic fat accumulation is
      specifically regulated during liver regeneration. Next, 2 methods were employed
      to disrupt hepatocellular fat accumulation in the regenerating liver. Because
      exogenous leptin supplementation reverses hepatic steatosis in leptin-deficient
      mice, the effects of leptin supplementation on liver regeneration in wild-type
      mice were examined. The data showed that leptin supplementation resulted in
      suppression of hepatocellular fat accumulation and impairment of hepatocellular
      proliferation during liver regeneration. Second, because glucocorticoids regulate
      cellular fat accumulation during adipocyte differentiation, the effects of
      hepatocyte-specific disruption of the glucocorticoid receptor were similarly
      evaluated. The results showed that hepatic fat accumulation and hepatocellular
      proliferation were also suppressed in mice with liver specific disruption of
      glucocorticoid receptor. In conclusion, suppression of hepatocellular fat
      accumulation is associated with impaired hepatocellular proliferation following
      partial hepatectomy, indicating that hepatocellular fat accumulation is
      specifically regulated during and may be essential for normal liver regeneration.

PMID- 15565661
TI  - PGE1-induced NO reduces apoptosis by D-galactosamine through attenuation of NF
      kappaB and NOS-2 expression in rat hepatocytes.
AB  - Prostaglandin E1 (PGE1) reduces cell death in experimental and clinical liver
      dysfunction. We have previously shown that PGE1 preadministration protects
      against NO-dependent cell death induced by D-galactosamine (D-GalN) through a
      rapid increase of nuclear factor kappaB (NF-kappaB) activity, inducible NO
      synthase (NOS-2) expression, and NO production. The present study investigates
      whether PGE1-induced NO was able to abolish NF-kappaB activation, NOS-2
      expression, and apoptosis elicited by D-GalN. Rat hepatocytes were isolated
      following the classical method of collagenase perfusion of liver. PGE1 (1
      micromol/L) was administered 2 hours before D-GalN (5 mmol/L) in primary culture
      rat hepatocytes. PGE1 reduced inhibitor kappaBalpha degradation, NF-kappaB
      activation, NOS-2 expression, and apoptosis induced by D-GalN. The administration
      of an inhibitor of NOS-2 abolished the inhibitory effect of PGE1 on NF-kappaB
      activation and NOS-2 expression in D-GalN-treated hepatocytes. Transfection
      studies using different plasmids corresponding to the NOS-2 promoter region
      showed that D-GalN and PGE1 regulate NOS-2 expression through NF-kappaB during
      the initial stage of hepatocyte treatment. PGE1 was able to reduce the promoter
      activity induced by D-GalN. In addition, a NO donor reduced NOS-2 promoter
      activity in transfected hepatocytes. In conclusion, administration of PGE1 to
      hepatocytes produces low levels of NO, which inhibits its own formation during D
      GalN-induced cell death through the attenuation of NF-kappaB-dependent NOS-2
      expression. Therefore, a dual role for NO in PGE1-treated D-GalN-induced toxicity
      in hepatocytes is characterized by a rapid NO release that attenuates the late
      and proapoptotic NOS-2 expression.

PMID- 15565662
TI  - Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice.
AB  - We investigated the effect of bone marrow cell (BMC) transplantation on
      established liver fibrosis. BMCs of green fluorescent protein (GFP) mice were
      transplanted into 4-week carbon tetrachloride (CCl4)-treated C57BL6 mice through
      the tail vein, and the mice were treated for 4 more weeks with CCl4 (total, 8
      weeks). Sirius red and GFP staining clearly indicated migrated BMCs existing
      along with fibers, with strong expression of matrix metalloproteinase (MMP)-9
      shown by anti-MMP-9 antibodies and in situ hybridization. Double fluorescent
      immunohistochemistry showed the expression of MMP-9 on the GFP-positive cell
      surface. Film in situ zymographic analysis revealed strong gelatinolytic activity
      in the periportal area coinciding with the location of MMP-9-positive BMCs. Four
      weeks after BMC transplantation, mice had significantly reduced liver fibrosis,
      as assessed by hydroxyproline content of the livers, compared to that of mice
      treated with CCl4 alone. Subpopulation of Liv8-negative BMCs was responsible for
      this fibrolytic effect. In conclusion, mice with BMC transplants with continuous
      CCl4 injection had reduced liver fibrosis and a significantly improved survival
      rate after BMC transplantation compared with mice treated with CCl4 alone. This
      finding introduces a new concept for the therapy of liver fibrosis.

PMID- 15565663
TI  - Prenatal diagnosis of complete trisomy 16q in two consecutive pregnancies.

PMID- 15565664
TI  - "Double-concave" graphene: permethoxylated hexa-peri-hexabenzocoronene and its
      cocrystals with hexafluorobenzene and fullerene.

PMID- 15565666
TI  - Gold redox catalysis for selective oxidation of methane to methanol.

PMID- 15565665
TI  - The chemical application of high-resolution electron tomography: bright field or
      dark field?

PMID- 15565667
TI  - Palladium-catalyzed enantioselective domino reaction for the efficient synthesis
      of vitamin E.

PMID- 15565668
TI  - Are beta-acylaminoacrylates hydrogenated in the same way as alpha
      acylaminoacrylates?

PMID- 15565669
TI  - Stereocontrolled creation of adjacent quaternary and tertiary stereocenters by a
      catalytic conjugate addition.

PMID- 15565670
TI  - Semiquantitative determination of Alicyclobacillus acidoterrestris in orange
      juice by reverse-transcriptase polymerase chain reaction and capillary
      electrophoresis--laser induced fluorescence using microchip technology.
AB  - The semiquantitative detection of Alicyclobacillus acidoterrrestris in orange
      juice by reverse-transcriptase polymerase chain reaction (RT-PCR) with a linear
      dynamic range of 2 x 10(5)-2 colony forming units (CFU)/mL in terms of cell count
      is described. Separation, detection, and quantification of the RT-PCR products
      were accomplished using the Agilent 2100 bioanalyzer in conjunction with the DNA
      1000 LabChip kit. After 0 and 12 h of enrichment, it was possible to generate a
      linear standard curve between the amount of cells and amplicon concentration of
      RT-PCR and PCR products. Using this method, cell diminution was verified in
      samples of orange juice treated with a natural inhibitor (Sapindus saponaria),
      determining the persistence of viable cells. Semiquantitative RT-PCR using the
      Agilent 2100 bioanalyzer is a potentially useful approach for rapid in vitro
      determination of A. acidoterrestris and monitoring of inhibitor susceptibility
      for the orange juice-producing industry.

PMID- 15565671
TI  - Separation of proteins by zone electrophoresis on-line coupled with
      isotachophoresis on a column-coupling chip with conductivity detection.
AB  - This feasibility study deals with the separations of proteins by an on-line
      combination of zone electrophoresis (ZE) with isotachophoresis (ITP) on a
      poly(methylmethacrylate) column-coupling (CC) chip with integrated conductivity
      detection. ITP and ZE provided specific analytical functions while performing the
      cationic mode of the separation. ITP served, mainly, for concentrations of
      proteins and its concentrating power was beneficial in reaching a low dispersion
      transfer (injection) of the proteinous constituents, loaded on the CC chip in a
      960 nL volume, into the ZE separation stage. This was complemented by an
      electrophoretically driven removal of the sample constituents migrating in front
      of the focused proteins from the separation system before the ZE separation. On
      the other hand, ZE served as a final separation (destacking) method and it was
      used under the separating conditions providing the resolutions and sensitive
      conductivity detections of the test proteins. In this way, ITP and ZE
      cooperatively contributed to low- or sub-microg/mL concentration detectabilities
      of proteins and their quantitations at 1-5 microg/mL concentrations. However, a
      full benefit in concentration detectabilities of proteins, expected from the use
      of the ITP-ZE combination, was not reached in this work. Small adsorption losses
      of proteins and detection disturbances in the ZE stage of separation, very likely
      due to trace constituents concentrated by ITP, appear to set limits in the
      detection of proteins in our experiments. The ITP-ZE separations were carried out
      in a hydrodynamically closed separation compartment of the chip with suppressed
      hydrodynamic and electroosmotic flows of the electrolyte solutions. Such
      transport conditions, minimizing fluctuations of the migration velocities of the
      separated constituents, undoubtedly contributed to highly reproducible migrations
      of the separated proteins (fluctuations of the migration time of a particular
      protein were typically 0.5% RSD in repeated ITP-ZE runs).

PMID- 15565672
TI  - Performance of electrokinetic supercharging for high-sensitivity detection of DNA
      fragments in chip gel electrophoresis.
AB  - Chip gel electrophoresis was explored for high-sensitivity detection of DNA by
      combining electrokinetic injection with transient isotachophoresis
      preconcentration (here named electrokinetic supercharging (EKS)). Low
      concentrations (0.2 mg/L) of DNA sample could be detected without fluorescence
      labeling using a conventional UV detector (at 260 nm). On a single-channel
      microchip, identification of PCR product was performed by exploiting both
      external and internal calibration methods. The deviation between the two
      calibration methods was about 3.6%, and the identified DNA fragment size matched
      with the predicted size of the template DNA. On the cross microchip the EKS
      preconcentration has also been achieved when changing the injection reservoir
      differing from the one used previously. The procedure was computer-simulated and
      the influence of the voltage applied to two-side reservoirs on sample
      preconcentration and dilution was also discussed.

PMID- 15565673
TI  - Quantitative polymerase chain reaction and microchip electrophoresis to detect
      major rearrangements of the low-density lipoprotein receptor gene causing
      familial hypercholesterolemia.
AB  - A variety of rearrangements in the low-density lipoprotein receptor (LDLR) gene
      cause severe forms of familial hypercholesterolemia (FH). However, current
      methods for searching these abnormalities in FH samples, e.g., Southern and
      Northern Blot, are labor-intensive and not routinely used by diagnostic
      laboratories. We developed a simpler approach based on the quantitative
      polymerase chain reaction (PCR) amplification of part or all gene's coding
      sequences by a series of multiplex amplifications comprising three nonadjacent
      gene sections plus a fourth section used as an internal reference. Thereafter,
      the analysis of these PCR products by microchip electrophoresis revealed either
      deletions or duplications in the investigated gene sections through the simple
      comparison of electropherograms obtained from mutant and control samples. This
      required primers leading to well-resolved peaks with minimal size differences
      among coamplified products and PCR conditions allowing a linear quantitative
      response to template amount variations as those caused by duplication or deletion
      of specific gene sections. Also, the inclusion of exon 17 amplification product
      as an internal reference in each multiplex PCR allowed the normalization of
      quantitative results by dividing the area of each amplified section by the area
      of exon 17. The comparison of these ratios calculated from 10 carriers of 6 LDLR
      known rearrangements with those obtained from 14 control samples showed that
      gross deletions roughly halved and duplications doubled the ratio values of exons
      involved in the mutation. This allowed to distinguish gross mutations from sample
      to-sample differences that reached at maximum 8% variation over mean values.

PMID- 15565674
TI  - Development of a chip-based capillary gel electrophoresis method for
      quantification of a half-antibody in immunoglobulin G4 samples.
AB  - A method based on microfluidic technology was developed to support quantitative
      analysis of recombinant monoclonal immunoglobulin G4 (IgG4) antibody samples. The
      assay was performed on an Agilent 2100 Bioanalyzer in combination with the
      Protein 200 Plus LabChip Kit and the Protein 200 Plus assay software. Capillary
      electrophoresis principles have been transferred to a chip format that integrates
      all separation, staining, virtual destaining, and detection steps. The method is
      referred to in this paper as chip-based capillary gel electrophoresis (GelChip-CE
      method). The GelChip-CE method under nonreducing conditions proved to be a
      quantitative test for half-antibody determination in IgG4 samples. Similar to the
      traditional nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) method, the GelChip-CE method includes a denaturing step prior to
      separation. We showed that denaturing the sample by heating resulted in an
      artificial increase in the amount of half-antibody detected, which could be
      prevented by addition of N-ethylmaleimide to the sample buffer. The GelChip-CE
      method allowed for analysis of IgG4 samples with more accuracy, higher precision,
      and a faster turnaround time than SDS-PAGE and reversed-phase high-performance
      liquid chromatography (RP-HPLC).

PMID- 15565678
TI  - Whole-column fluorescence-imaged capillary electrophoresis.
AB  - An axially illuminating whole-column fluorescence imaging capillary
      electrophoresis (CE) experimental setup was developed. A 6 cm long Teflon tube
      with an inside diameter (ID) of 42 microm was used as separation column.
      Excitation light of 488 nm from Ar+ laser was introduced to one end of the
      separation column by an optical fiber. The excitation light propagated inside the
      separation column by total internal reflection, since the refractive index of the
      buffer solution was larger than that of the Teflon tube. The fluorescence from
      the whole separation column was imaged with a charge-coupled device (CCD) camera.
      Fluorescent compounds such as fluorescein isothiocyanate (FITC), 5
      carboxyfluorescein, and FITC-labeled protein were used to test the basic
      performance of the experimental setup. Experimental results illustrate that the
      whole-column-fluorescence imaging CE is a fast and sensitive separation method
      for fluorescent compounds and fluorescent-labeled proteins. Furthermore, it could
      be used for simple, fast, and easy comparisons of the resistance to
      photodegradation for various fluorescent compounds.

PMID- 15565677
TI  - Near-infrared time-resolved fluorescence lifetime determinations in
      poly(methylmethacrylate) microchip electrophoresis devices.
AB  - High aspect-ratio microstructures were hot-embossed in polymer substrates with a
      molding tool fabricated using lithography/electroplating/forming (LIGA). The
      resulting devices were used for the electrophoretic separation of
      oligonucleotides labeled with near-infrared (near-IR) dyes. Near-IR time-resolved
      fluorescence was used as an identification method for the labeling dyes. The
      detection apparatus consisted of a pulsed laser diode operating at 680 nm, a
      single-photon avalanche diode, an integrated microscope, and a PC-board
      incorporating time-correlated single photon counting electronics. Investigation
      of the optical quality and amount of autofluorescence generated from different
      polymer substrates was carried out in the near-IR region for determining
      compatibility with time-resolved fluorescence. Our results revealed that of
      several poly(methylmethacrylate)(PMMA) substrates, brand Plexiglas offered
      minimal replication errors in the embossed features using appropriate embossing
      conditions with low background fluorescence contributions to the observed decay.
      Near-IR dye-labeled oligonucleotides were separated to determine the
      applicability of fluorescence lifetime discrimination between Cy5.5 (tauf = 930
      ps) and IRD700 (tauf = 851 ps) labeling dyes during the microchip separation.
      These dyes were used to label T-fragments (thymine) of an M13mp18 ssDNA template.
      The DNA ladders were electrophoresed at 130 V/cm in a 4% linear polyacrylamide
      gel (LPA) gel matrix in a 9.5 cm long serpentine channel heated to 50 degrees C.
      The electropherogram revealed that the lifetimes could be accurately read well
      beyond 450 bases, although single-base pair resolution in the electropherogram
      was difficult to achieve due to potential solute-wall interactions in the polymer
      microdevice or the electroosmotic flow (EOF) properties of the device. The
      relative standard deviations secured for individual bands in the electropherogram
      were similar to those obtained using capillary gel electrophoresis, in spite of
      the lower load volume.

PMID- 15565679
TI  - Microfluidic devices obtained by thermal toner transferring on glass substrate.
AB  - A new process for the manufacture of microfluidic devices based on deposition of
      laser-printing toner on glass substrates is described. It is an alternative
      method to the toner on polyester film (toner-polyester) one, previously
      introduced. Commercial laser printers cannot print directly on glass, thus the
      toner must first be printed on a special paper and then transferred by heating
      under pressure to the glass surface. Although this procedure is more complex than
      the toner-polyester one, it can be repeated several times, yielding multiple
      toner layers. Even without special alignment equipment, up to four layers could
      be satisfactorily piled up. Characterization tests revealed that the toner-glass
      devices have similar behavior as toner-polyester ones regarding the toner layer
      porosity. The main advantages of the toner-glass technology are improved
      mechanical stability, possibility of multiple toner layers, augmented
      electroosmotic flow (EOF), and improved heat transfer. On the other hand, toner
      adhesion to glass is weaker than to polyester, which limits the device lifetime
      and usable liquid media. The measured EOF mobility (3.5 x 10(-4) cm2.V(-1).s(-1)
      for pH 7) suggests that it is mainly determined by the glass surface, being
      little influenced by the toner walls. Microchip electrophoresis with contactless
      conductivity detection and photometric detection were implemented using toner
      glass devices.

PMID- 15565680
TI  - Electrophoresis microchip fabricated by a direct-printing process with end
      channel amperometric detection.
AB  - We describe the development of an electrophoresis microchip fabricated by a
      direct-printing process, based on lamination of printed polyester films with end
      channel amperometric detection. The channel structures are defined by polyester
      (base and cover) and by a toner layer (walls). The polyester-toner devices
      presented an electroosmotic flow (EOF) magnitude of approximately 10(-5) cm2 V(
      1) s(-1), which is generated by a polymeric mixture of the toner and polyester
      composition. The microelectrodes used for detection were produced combining this
      laser-printer technology to compact discs. The performance of this device was
      evaluated by amperometric detection of iodide and ascorbate. The detection limits
      found were 500 nmol.L(-1) (135 amol) and 1.8 micromol.L(-1) (486 amol) for iodide
      and ascorbate, respectively.

PMID- 15565681
TI  - Photopolymerized microtips for sample preparation in proteomic analysis.
AB  - We demonstrate a novel method for the fabrication of disposable plastic
      microtips, which we name "EasyTip", by a photopolymerization technique. C18
      reversed-phase (C18) and ion metal affinity chromatography (IMAC) beads were
      immobilized on a plastic pipette tip, made of polypropylene materials, by photo
      initiated polymerization. The fabricated EasyTips can be manipulated using
      commercial pipettes for wash/elution of minute amount of biological samples (< 10
      microL) and can be applied for mass spectrometry (MS)-based proteomic analysis,
      in which the detection sensitivity depends critically on the optimal sample
      preparation. The recovery of a sample of 25 fmol of tryptic hemoglobin digest
      loaded in a C18 EasyTip was near 100% and we estimated the loading capacity to be
      around 0.4-2.0 microg of total proteins or peptides, which is well above a
      sufficient quantity for MS analysis. The effectiveness of the C18 EasyTips in
      enhancing the detection sensitivity of matrix-assisted laser
      desorption/ionization (MALDI)-MS signal, and thus providing a greater sequence
      coverage, was also demonstrated by the analysis of hemoglobin digest and the in
      gel digested epidermal growth factor receptor (EGFR) protein from A431 cell
      lysate. We also demonstrated the usefulness of the immobilized IMAC EasyTips in
      extracting the signal of tryptic phosphopeptides of beta-casein (10 pmol) having
      one and four phosphorylation sites by using an IMAC EasyTip prior to off-line
      analysis by MS. The combination of IMAC EasyTips and MALDI-MS allowed the
      unambiguous identification of phosphopeptides based on the phosphatase assay as
      well as the post-source decay. Compared to other miniaturized devices, this
      fabrication method is simple, cheap, and requires less human intervention.
      Moreover, the method of manipulating the EasyTips is straightforward and can be
      automated readily by a robotic system for high-throughput analysis.

PMID- 15565682
TI  - Subsecond chiral separations on a microchip.
AB  - Fast chiral separation of DNS-amino acids could be realized using microchip
      electrophoresis with fluorescence detection. For this purpose, highly sulfated
      cyclodextrins (HS-gamma-CD) were used as chiral selectors enabling high
      selectivity. Even subsecond separation of DNS-tryptophan, DNS-norleucine, DNS
      phenylalanine, DNS-methionine, and DNS-aspartic acid could be achieved. Baseline
      separation could be accomplished within 720 ms, which is the fastest separation
      of enantiomers reported to date. A more complex mixture consisting of three
      chiral DNS-amino acids could be separated within 3.3 s utilizing a separation
      length of only 7 mm and an electrical field strength of 2012 V/cm.

PMID- 15565683
TI  - Direct electrochemical detection of glucose in human plasma on capillary
      electrophoresis microchips.
AB  - We developed an electrochemical detector on a hybrid chip for the determination
      of glucose in human plasma. The microchip system described in this paper consists
      of a poly(dimethylsiloxane) (PDMS) layer containing separation and injection
      channels and an electrode plate. The copper microelectrode is fabricated by
      selective electroless deposition. The fabrication of the decoupler is performed
      by platinum electrochemical deposition on the metal film formed by electroless
      deposition. Factors influencing the performance, including detection potential,
      separation field strength, and buffer concentration, were studied. The electrodes
      exhibited good stability and durability in the analytical procedures. Under
      optimized detection conditions, glucose responded linearly from 10 microM to 1
      mM. Finally, glucose in human plasma from three healthy individuals and two
      diabetics was successfully determined, giving a good prospect for a new clinical
      diagnostic instrument.

PMID- 15565684
TI  - Neuron-based microarray sensors for environmental sensing.
AB  - We present a novel sensing scheme for detecting the effects of unburned fossil
      fuels by integrating microarray technology and dielectrophoresis to develop
      single-neuron arrays. These arrays have the capability to sense and identify the
      two fuels, at parts per billion (ppb) concentrations, as well to determine the
      associated physiological changes at the single-cell level. Identification is
      achieved through frequency domain analysis of the measured changes to the
      extracellular electrical activity due to the effect of the fossil fuels. This
      yields unique electrical identifiers known as "signature patterns". Simultaneous
      optical visualization to the physiological changes is obtained by specific
      fluorescent staining. The correlation between the signature patterns and the
      cellular biological behavior establishes the veracity of this identification
      technique.

PMID- 15565685
TI  - Gravity-induced convective flow in microfluidic systems: electrochemical
      characterization and application to enzyme-linked immunosorbent assay tests.
AB  - A way of using gravity flow to induce a linear convection within a microfluidic
      system is presented. It is shown and mathematically supported that tilting a 1 cm
      long covered microchannel is enough to generate flow rates up to 1000 nL.min(-1),
      which represents a linear velocity of 2.4 mm.s(-1). This paper also presents a
      method to monitor the microfluidic events occurring in a covered microchannel
      when a difference of pressure is applied to force a solution to flow in said
      covered microchannel, thanks to electrodes inserted in the microfluidic device.
      Gravity-induced flow monitored electrochemically is applied to the performance of
      a parallel-microchannel enzyme-linked immunosorbent assay (ELISA) of the thyroid
      stimulating hormone (TSH) with electrochemical detection. A simple method for
      generating and monitoring fluid flows is described, which can, for instance, be
      used for controlling parallel assays in microsystems.

PMID- 15565686
TI  - Integrated selective enrichment target--a microtechnology platform for matrix
      assisted laser desorption/ionization-mass spectrometry applied on protein
      biomarkers in prostate diseases.
AB  - The performance of a miniaturized sample processing platform for matrix-assisted
      laser desorption/ionization-mass spectrometry (MALDI-MS), manufactured by silicon
      microfabrication, called integrated selective enrichment target (ISET) technology
      was evaluated in a biological context. The ISET serves as both sample treatment
      device and MALDI-MS target, and contains an array of 96 perforated nanovials,
      which each can be filled with 40 nL of reversed-phase beads. This methodology
      minimizes the number of sample transfers and the total surface area available for
      undesired adsorption of the analytes in order to provide high-sensitivity
      analysis. ISET technology was successfully applied for characterization of
      proteins coisolated by affinity chromatography of prostate-specific antigen (PSA)
      from human seminal fluid. The application of ISET sample preparation enabled
      multiple analyses to be performed on a limited sample volume, which resulted in
      the discovery that prolactin inducible protein (PIP) was coisolated from the
      samples.

PMID- 15565687
TI  - Autonomous protein sample processing on-chip using solid-phase microextraction,
      capillary force pumping, and microdispensing.
AB  - A capillary force filling microsystem consisting of a chip-integrated solid-phase
      microextraction (SMEC) array and a microdispenser for sample purification and
      trace enrichment of peptides is described. The microextraction array was loaded
      with solid-phase media (50 microm Poros R2 beads) for purification and enrichment
      of proteomic samples. Samples bound to the SMEC were eluted in a volume of 200
      nL. A piezo-electric microdispenser was docked to the array and the samples bound
      to the SMEC were eluted in a volume of 200 nL using capillary forces. The
      purified and enriched samples were dispensed onto the matrix-assisted laser
      desorption/ionization (MALDI) target, providing quality data from samples in the
      picomolar range. The nanoproteomic platform was compared to corresponding
      commercial preparation protocols, showing higher mass spectrometry (MS) signal
      intensities for peptides generated from an alpha-casein digest. The platform was
      also evaluated with regards to two-dimensional (2-D) gel-derived protein digests
      from both fibroblast and epithelial target cells.

PMID- 15565688
TI  - Pure-silica optical waveguides, fiber couplers, and high-aspect ratio
      submicrometer channels for electrokinetic separation devices.
AB  - A new fabrication procedure for integration of ultraviolet transparent pure
      silica planar waveguides, fiber couplers and high-aspect ratio submicrometer
      channels is presented. Only a single photolithographic mask step is required. The
      channels are 80-90 microm deep and the width can be reduced to about 0.5 microm,
      corresponding to a height-to-width ratio of more than 150. The core of the
      waveguides consists of pure silicon dioxide, which is favorable over doped
      silica, due to the absence of absorption centers associated with the dopants.
      This furthermore improves the long-term stability of the waveguides, because of
      an increased radiation resistance of the glass. The propagation loss decreases
      from 1.0 dB/cm at 200 nm to 0.2 dB/cm at 800 nm, which, to our knowledge, is the
      lowest propagation loss reported for integrated planar waveguides in the
      ultraviolet wavelength region to date. The effective optical path length is 1.2
      mm for an absorbance cell with a nominal length of 1.0 mm, indicating effective
      suppression of stray light. The limit of detection for paracetamol when present
      in the entire channel network was determined to 3 microg/mL. Finally, the
      applicability of the fabricated devices for capillary electrophoresis was
      evaluated by separation of caffein, paracetamol and ketoprofone using absorbance
      detection at 254 nm.

PMID- 15565689
TI  - High-power blue/UV light-emitting diodes as excitation sources for sensitive
      detection.
AB  - With advances in III-V nitride manufacturing processes, high-power light-emitting
      diode (LED) chips in the blue and UV wavelengths are now commercially available
      at reasonable cost and can be used as excitation sources in optical sensing. We
      describe the use of these high-power blue and UV LEDs for sensitive fluorescence
      detection, including chip-based flow cytometry, capillary electrophoresis (CE),
      and single-molecule imaging. By using a blue LED with a focusable power of
      approximately 40 mW as the excitation source for fluorescent beads, we
      demonstrate a simple chip-based bead sorter capable of enriching the
      concentration of green fluorescent beads from 63% to 95%. In CE experiments, we
      show that a mixture of analyte solution containing 30 nM 6-carboxyrhodamine 6G
      and 10 nM fluorescein can be separated and detected with excellent signal-to
      noise ratio (approximately 17 for 10 nM fluorescein) using the collimated
      emission from a blue LED; the estimated mass detection limit was approximately
      200 zmol for fluorescein. We also demonstrated ultrasensitive fluorescence
      imaging of single rhodamine 123 molecules and individual lambda-DNA molecules. At
      a small fraction of the cost of an Ar+ laser, high-power blue and UV LEDs are
      effective alternatives for lasers and arc lamps in fluorescence applications that
      demand portability, low cost, and convenience.

PMID- 15565690
TI  - Noninvasive fluid flow measurements in microfluidic channels with backscatter
      interferometry.
AB  - The ability to measure fluid velocity within picoliter volumes or on-chip
      noninvasively, is important toward fully realizing the potential of microfluidics
      and micrototal analysis systems, particularly in applications such as micro-high
      performance liquid chromatography (HPLC) or in metering mixing where the flow
      rate must be quantified. Additionally, these measurements need to be performed
      directly on moving fluids in a noninvasive fashion. We presented here the proof
      of principle experiments showing nonintrusive fluid flow measurements can be
      accomplished on-chip using a pump and probe configuration with backscattering
      interferometry. The on-chip interferometric backscatter detector (OCIBD) is based
      on a fiber-coupled HeNe laser that illuminates a portion of an isotropically
      etched 40 microm radius channel and a position sensitive transducer to measure
      fringe pattern shifts. An infrared laser with a mechanical shutter is used to
      heat a section of a flowing volume and the resulting refractive index (RI) change
      is detected with the OCIBD downstream as a time-dependent RI perturbation. Fluid
      velocity is quantified as changes in the phase difference between the shutter
      signal and the OCIBD detected signal in the Fourier domain. The experiments are
      performed in the range of 3-6 microL/h with 3sigma detection limits determined to
      be 0.127 nL/s. Additionally, the RI response of the system is calibrated using
      temperature changes as well as glycerol solutions.

PMID- 15565691
TI  - Electrokinetic pumping and detection of low-volume flows in nanochannels.
AB  - Electrokinetic pumping of low-volume rates was performed on-chip in channels of
      small cross sectional area and height in the sub-microm range. The flow was
      detected with the current monitoring technique by monitoring the change in
      resistance of the fluid in the channel upon the electroosmosis-driven
      displacement of an electrolyte solution by a second electrolyte solution. Flow
      rates in the order of 0.1 pL/s were successfully generated and detected. The
      channels were fabricated with the sacrificial layer technology.

PMID- 15565692
TI  - Peak compression and resolution for electrophoretic separations in diverging
      microchannels.
AB  - We report the results of experiments and simulations on electrokinetic flow in
      diverging microchannels (with cross-sectional area that increases with distance
      along the channel). Because of conservation of mass and charge, the velocity of
      an analyte in the channel decreases as the channel cross-section increases.
      Consequently, the leading edge of a band of sample moves more slowly than the
      trailing edge and the sample band is compressed. Sample peak widths, rather than
      increasing diffusively with time, can then be controlled by the geometry of the
      channel and can even be made to decrease with time. We consider the possibility
      of using this peak compression effect to improve the resolution of
      electrophoretic separations. Our results indicate that for typical separations
      that are dispersion limited, this peak compression effect is more than offset by
      the decreased distance between peaks, and the separation resolution in diverging
      channels is worse than that found for straight channels at the same applied
      voltage. For separations in very short channels or at very high field strengths,
      however, when the separation efficiency is injection limited, the peak
      compression effect is dominant and diverging channels can then be used to achieve
      improved separation resolution.

PMID- 15565693
TI  - Electroosmotic guiding of sample flows in a laminar flow chamber.
AB  - The so-called address-flow principle is described: a valveless,
      electroosmotically driven technology used for controlling the stream profile in a
      laminar flow chamber. The method is explained, and a theoretical description and
      experimental verification are presented. Adjustment of the flow of two
      electroosmotically controlled guiding streams, running parallel to a central
      sample stream, can be used for positioning the sample stream in the dimension
      perpendicular to the flow direction. The results presented show that address-flow
      microfluidics allow easy and accurate control of sample stream position and
      width. The electroosmotic flow (EOF)-controlled guiding of microfluidic flows
      described in this paper, is a new unit operation that might aid in separation and
      collection in microfluidic devices. One possible application of address-flow
      microfluidics is guiding of capillary electrophoresis-separated components over a
      multisensor array, in order to perform affinity assays.

PMID- 15565694
TI  - Genotyping by dynamic heating of monolayered beads on a microheated surface.
AB  - A miniaturized bead-based dynamic allele-specific hybridization (DASH) approach
      for single-nucleotide polymorphism analysis is presented. Chips with integrated
      heater and temperature sensors for open-surface DNA analysis were
      microfabricated. Microcontact printing using a poly(dimethylsiloxane) (PDMS)
      stamp was employed to create monolayers of immobilized beads on the surface of
      the chip. This chip allows fast, well-controllable temperature ramping. The
      temperature distribution was homogeneous over the entire heater area. All three
      possible variants of an SNP site of a synthesized oligonucleotide were accurately
      scored using the bead-based DASH approach. Our assay has a nonoptimized
      temperature ramping rate of 4 degrees C-6 degrees C/min compared to earlier
      reported values of 2 degrees C-3 degrees C/min, thereby reducing the total
      analysis time by a factor of 2. Reliable DASH measurement data from areas as
      small as 12 x 13 microm was achieved. Our bead-based DASH approach has enabled a
      dramatic volume reduction and is a step towards developing a cost-effective high
      throughput DASH method on arrays of single beads.

PMID- 15565695
TI  - A simple mechanism for reliable particle sorting in a microdevice with combined
      electroosmotic and pressure-driven flow.
AB  - Selective transport and sorting of particles in microfluidic devices by
      electroosmosis is complicated due to superposition of uncontrolled hydrodynamic
      pressure contributions on the electroosmotic force. In this paper, we present a
      microfluidic concept for the reliable and simple separation and sorting of
      particles in a microchip by electroosmosis combined with pressure-driven flow.
      The presented device allows fluid quantities to be switched and particles to be
      sorted within a channel manifold using only a single power supply with fixed
      voltage and an electric switch. Consequently, chip operation and fluid switching
      procedure are greatly simplified compared to a situation, in which several
      independent power sources are used for flow balancing, as is the common
      procedure. With the triple-T channel design presented, backpressure flow
      disturbing the electrokinetic fluid and particle separation process is eliminated
      by introducing controlled opposed hydrodynamic flow of buffer from side channels.
      This pressure-driven flow is generated on-chip by setting up differences in the
      reservoir pressures in a defined manner. A detailed flow analysis based on the
      equivalence of fluid flow and electric current is performed and the conditions
      for reliable chip function are worked out.

PMID- 15565696
TI  - Microbead-based affinity chromatography chip using RNA aptamer modified with
      photocleavable linker.
AB  - A microbead-based affinity chromatography chip (micro-BACC) controlling hundreds
      of nanoliters of reaction volume was developed to separate and analyze hepatitis
      C virus (HCV) RNA polymerase protein by immobilization of an RNA aptamer on
      beads. A photocleavable linker was conjugated in between the beads and the
      aptamer to elute the bound RNA polymerase from the RNA aptamer in one step by UV
      irradiation, resulting in an efficient method to elute and identify the target
      molecule bound on RNA using a mass spectrometer. This linker showed a cleavage
      activity over 70% upon UV irradiation at 1050 mW/cm2 for more than 5 min. The
      photoelution method could prevent the target molecule from contaminations in
      affinity chromatography caused by elution solutions of high salt concentration,
      extreme pH and detergent, respectively. In this chip, sample reagents up to 800
      nL could be metered quantitatively into the bead chamber using a nanoliter
      dispenser working, based on surface-guided flow control and pneumatic control by
      external air pressure on the chip. RNA polymerase eluted after UV irradiation was
      successfully analyzed by trypsin treatment without additional purification. As a
      result, using the aptamer, we could detect RNA polymerase from 800 nL hepatitis C
      patient serum containing 96 fmol HCV RNA polymerase. The detection limit of this
      system was estimated to be 9.6 fmol HCV RNA polymerase.

PMID- 15565697
TI  - The potential of autofluorescence for the detection of single living cells for
      label-free cell sorting in microfluidic systems.
AB  - A novel method for studying unlabeled living mammalian cells based on their
      autofluorescence (AF) signal in a prototype microfluidic device is presented.
      When combined, cellular AF detection and microfluidic devices have the potential
      to facilitate high-throughput analysis of different cell populations. To
      demonstrate this, unlabeled cultured cells in microfluidic devices were excited
      with a 488 nm excitation light and the AF emission (> 505 nm) was detected using
      a confocal fluorescence microscope (CFM). For example, a simple microfluidic
      three-port glass microstructure was used together with conventional
      electroosmotic flow (EOF) to switch the direction of the fluid flow. As a means
      to test the potential of AF-based cell sorting in this microfluidic device,
      granulocytes were successfully differentiated from human red blood cells (RBCs)
      based on differences in AF. This study demonstrated the use of a simple
      microfabricated device to perform high-throughput live cell detection and
      differentiation without the need for cell-specific fluorescent labeling dyes and
      thereby reducing the sample preparation time. Hence, the combined use of
      microfluidic devices and cell AF may have many applications in single-cell
      analysis.

PMID- 15565698
TI  - Dielectrophoresis of nanoparticles.
AB  - A numerical scheme based on the distributed Lagrange multiplier method (DLM) is
      used to study the motion of nano-sized particles of dielectric suspensions
      subjected to uniform and nonuniform electric fields. Particles are subjected to
      both electrostatic and hydrodynamic forces, as well as Brownian motion. The
      results of the simulations presented in this paper show that uniform electric
      fields the evolution of the particle structures depends on the ratio of
      electrostatic particle-particle interactions and Brownian forces. When this ratio
      is of the order of 100 or greater, particles form stable chains and columns,
      whereas when it is of the order of 10 or smaller the particle distribution is
      random. For the nonuniform electric field cases considered in this paper, the
      relative magnitude of Brownian forces is in the range such that it does not
      influence the eventual collection of particles by dielectrophoresis and the
      particular locations where the particles are collected. However, Brownian motion
      is observed to influence the transient particle trajectories. The deviation of
      the particle trajectories compared to those determined by the electrostatic and
      hydrodynamic forces alone is characterized by the ratio of Brownian and
      dielectrophoretic forces.

PMID- 15565699
TI  - Unsteady transport phenomena in free-flow electrophoresis--prerequisite of
      ultrafast sample cleaning in microfluidic devices.
AB  - The evolution partial differential equations describing the transport processes
      induced by hydrodynamic flow in free-flow electrophoresis (FFE) are solved by the
      generalized dispersion theory. Our theoretical analysis demonstrates that the
      central injection of solutes into a relatively fast hydrodynamic flow enables to
      transport them to the channel outlet well before they are spread through the
      width of the channel and their migration is negatively affected by a contact with
      walls. In this case, the axial zone spreading decreases by increasing the linear
      velocity of hydrodynamic flow. The resulting dependencies of convective and
      dispersion coefficients on the velocity of flow and parameters of the separation
      channel show the optimum separation conditions with respect to resolution and
      analysis time. Due to the unsteady character of transport processes, effective
      FFE separations can potentially be performed in a microfluidic device in seconds.
      This is a reasonable time to separate low-molecular mass impurities in the
      electric field. Thus, a fast and efficient sample cleaning before subsequent
      analysis by electrospray ionization-mass spectrometry (ESI-MS) or another
      separation method can be performed.

PMID- 15565700
TI  - Parallel isoelectric focusing II.
AB  - A miniature electrophoretic device is developed on the basis of a new isoelectric
      focusing (IEF) method, namely parallel isoelectric focusing. We report here the
      theory and the results of operation of a new parallel isoelectric device (PID).
      The main advantages and limitations of the method are discussed for
      miniaturization purposes. It is shown that the method guarantees the fast and
      complete separation of any complex protein mixtures under acceptable conditions,
      such as voltage source, temperature, size of the device, and separation process
      duration. It is shown that the main problem of PID miniaturization is the buffer
      design, and the relation between Immobiline buffer capacity and solution buffer
      capacity. The main experimental limitation of PID resolution is protein
      sensitivity to pH changes.

PMID- 15565701
TI  - High-resolution DNA separation in microcapillary electrophoresis chips utilizing
      double-L injection techniques.
AB  - An experimental and numerical investigation into the use of high-resolution
      injection techniques to separate DNA fragments within electrophoresis microchips
      is presented. The principal material transport mechanisms of electrokinetic
      migration, fluid flow, and diffusion are considered, and several variable-volume
      injection methods are discussed. A detailed analysis is provided of a double-L
      injection technique, which employs appropriate electrokinetic manipulations to
      reduce sample leakage within the microchip. The leakage effect in electroosmotic
      flow (EOF) is investigated using a sample composed of rhodamine B and Cy3 dye.
      Meanwhile, the effects of sample leakage in capillary electrophoresis (CE)
      separation are studied by considering the separation of 100-base pairs (bp) DNA
      ladders and HaeIII-digested PhiX-174 DNA samples. The present experimental and
      simulation results indicate that the unique injection system employed in the
      current microfluidic chip has the ability to replicate the functions of both the
      conventional cross-channel and the shift-channel injection systems. Furthermore,
      applying the double-L injection method to these two injection systems is shown to
      reduce sample leakage significantly. The proposed microfluidic chip and double-L
      injection technique developed in this study have an exciting potential for use in
      high-resolution, high-throughput biochemical analysis applications and in many
      other applications throughout the micrototal analysis systems field.

PMID- 15565702
TI  - Nanowires for surface enlargement of narrow-bore fused-silica tubing.
AB  - A method for preparation of silica nanowires with dimensions of d = 10-100 nm, l
      = 5-500 nm, is described. The nanostructured material is an integral part of the
      inner surface of narrow bore fused-silica capillary tubing. The wire preparation
      method is based on a decomposition of 2-chloro-1,1,2-trifluoroethyl methyl ether
      at elevated temperature and pressure. The silica bulk material is rearranged via
      a sustained silica-hydrogen fluoride chemistry, and reaction mechanisms for this
      process are proposed. The method is suitable for preparing long lengths of tubing
      with the modified surface. It is our belief that the texture of the capillary
      wall with its increased surface area is useful for applications such as
      microreactions, catalysis, and high-resolution pressure and/or electrodriven open
      tubular liquid chromatography.

PMID- 15565703
TI  - Enzymatic reaction of the immobilized enzyme on porous silicon studied by matrix
      assisted laser desorption/ionization-time of flight-mass spectrometry.
AB  - Desorption/ionization on silicon mass spectrometry (DIOS-MS) is a matrix-free
      technique that allows for the direct desorption/ionization of low-molecular
      weight compounds with little or no fragmentation of analytes. This technique has
      a relatively high tolerance for contaminants commonly found in biological
      samples. DIOS-MS has been applied to determine the activity of immobilized
      enzymes on the porous silicon surface. Enzyme activities were also monitored with
      the addition of a competitive inhibitor in the substrate solution. It is
      demonstrated that this method can be applied to the screening of enzyme
      inhibitors. Furthermore, a method for peptide mapping analysis by in situ
      digestion of proteins on the porous silicon surface modified by trypsin, combined
      with matrix-assisted laser desorption/ionization-time of flight-MS has been
      developed.

PMID- 15565704
TI  - Exploiting the benefits of miniaturization for the enhancement of DNA
      microarrays.
AB  - The present study demonstrates that the best way to enhance DNA microarray
      assays, both in terms of analysis speed and in final spot intensity, is to
      dissolve the available molar amount of sample in the smallest possible buffer
      volume and to subsequently convect this solution continuously across the surface
      of the array. The presently proposed shear-driven flow system is pre-eminently
      suited for this task, as it allows to induce strongly enhanced lateral transport
      rates, independently of the degree of miniaturization of the hybridization
      chamber. This transport enhancement method, however, only increases the
      hybridization rate and not the final spot intensity, as neither can any of the
      other transport enhancement methods already proposed in literature. A series of
      experiments with synthetic single-stranded (ssDNA) samples and an accompanying
      mass balance analysis are presented to demonstrate these points.

PMID- 15565705
TI  - Recent developments in detection for microfluidic systems.
AB  - Microfluidic systems have become more and more important in the field of
      analytical chemistry. Detection methods on these microsystems are essential for
      the identification and quantification of chemical species that are being
      analyzed. This review concentrates on the latest developments of optical
      detection methods and mass spectrometry in conjunction with microfluidic systems.
      Electrochemical methods are discussed in another review in the same issue of this
      journal. Within the optical detection section, topics such as multiplexed
      detection and the use of waveguides are discussed. Within the discussion of mass
      spectrometry, the main focus is on electrospray emitters as interfaces between
      microsystem and spectrometer. Apart from optical detection and mass spectrometry,
      other techniques such as flame ionization and nuclear magnetic resonance are also
      mentioned.

PMID- 15565706
TI  - Fundamentals and practice for ultrasensitive laser-induced fluorescence detection
      in microanalytical systems.
AB  - Laser-induced fluorescence is an extremely sensitive method for detection in
      chemical separations. In addition, it is well-suited to detection in small
      volumes, and as such is widely used for capillary electrophoresis and microchip
      based separations. This review explores the detailed instrumental conditions
      required for sub-zeptomole, sub-picomolar detection limits. The key to achieving
      the best sensitivity is to use an excitation and emission volume that is matched
      to the separation system and that, simultaneously, will keep scattering and
      luminescence background to a minimum. We discuss how this is accomplished with
      confocal detection, 90 degrees on-capillary detection, and sheath-flow detection.
      It is shown that each of these methods have their advantages and disadvantages,
      but that all can be used to produce extremely sensitive detectors for capillary-
      or microchip-based separations. Analysis of these capabilities allows prediction
      of the optimal means of achieving ultrasensitive detection on microchips.

PMID- 15565707
TI  - Recent developments in electrochemical detection for microchip capillary
      electrophoresis.
AB  - Significant progress in the development of miniaturized microfluidic systems has
      occurred since their inception over a decade ago. This is primarily due to the
      numerous advantages of microchip analysis, including the ability to analyze
      minute samples, speed of analysis, reduced cost and waste, and portability. This
      review focuses on recent developments in integrating electrochemical (EC)
      detection with microchip capillary electrophoresis (CE). These detection modes
      include amperometry, conductimetry, and potentiometry. EC detection is ideal for
      use with microchip CE systems because it can be easily miniaturized with no
      diminution in analytical performance. Advances in microchip format, electrode
      material and design, decoupling of the detector from the separation field, and
      integration of sample preparation, separation, and detection on-chip are
      discussed. Microchip CEEC applications for enzyme/immunoassays, clinical and
      environmental assays, as well as the detection of neurotransmitters are also
      described.

PMID- 15565708
TI  - Immobilized microfluidic enzymatic reactors.
AB  - The use of enzymes for cleavage, synthesis or chemical modification represents
      one of the most common processes used in biochemical and molecular biology
      laboratories. The continuing progress in medical research, genomics, proteomics,
      and related emerging biotechnology fields leads to exponential growth of the
      applications of enzymes and the development of modified or new enzymes with
      specific activities. Concurrently, new technologies are being developed to
      improve reaction rates and specificity or perform the reaction in a specific
      environment. Besides large-scale industrial applications, where typically a large
      processing capacity is required, there are other, much lower-scale applications,
      benefiting form the new developments in enzymology. One such technology is
      microfluidics with the potential to revolutionize analytical instrumentation for
      the analyses of very small sample amounts, single cells or even subcellular
      assemblies. This article aims at reviewing the current status of the development
      of the immobilized microfluidic enzymatic reactors (IMERs) technology.

PMID- 15565709
TI  - DNA sequencing and genotyping in miniaturized electrophoresis systems.
AB  - Advances in microchannel electrophoretic separation systems for DNA analyses have
      had important impacts on biological and biomedical sciences, as exemplified by
      the successes of the Human Genome Project (HGP). As we enter a new era in genomic
      science, further technological innovations promise to provide other far-reaching
      benefits, many of which will require continual increases in sequencing and
      genotyping efficiency and throughput, as well as major decreases in the cost per
      analysis. Since the high-resolution size- and/or conformation-based
      electrophoretic separation of DNA is the most critical step in many genetic
      analyses, continual advances in the development of materials and methods for
      microchannel electrophoretic separations will be needed to meet the massive
      demand for high-quality, low-cost genomic data. In particular, the development
      (and commercialization) of miniaturized genotyping platforms is needed to support
      and enable the future breakthroughs of biomedical science. In this review, we
      briefly discuss the major sequencing and genotyping techniques in which high
      throughput and high-resolution electrophoretic separations of DNA play a
      significant role. We review recent advances in the development of technology for
      capillary electrophoresis (CE), including capillary array electrophoresis (CAE)
      systems. Most of these CE/CAE innovations are equally applicable to
      implementation on microfabricated electrophoresis chips. Major effort is devoted
      to discussing various key elements needed for the development of integrated and
      practical microfluidic sequencing and genotyping platforms, including chip
      substrate selection, microchannel design and fabrication, microchannel surface
      modification, sample preparation, analyte detection, DNA sieving matrices, and
      device integration. Finally, we identify some of the remaining challenges, and
      some of the possible routes to further advances in high-throughput DNA sequencing
      and genotyping technologies.

PMID- 15565710
TI  - Wall coating for capillary electrophoresis on microchips.
AB  - This review article with 116 references describes recent developments in the
      preparation of wall coatings for capillary electrophoresis (CE) on a microchip.
      It deals with both dynamic and permanent coatings and concentrates on the most
      frequently used microchip materials including glass, poly(methyl methacrylate),
      poly(dimethyl siloxane), polycarbonate, and poly(ethylene terephthalate glycol).
      Characterization of the channel surface by measuring electroosmotic mobility and
      water contact angle of the surface is included as well. The utility of the
      microchips with coated channels is demonstrated by examples of CE separations on
      these chips.

PMID- 15565711
TI  - Determination of inorganic ions using microfluidic devices.
AB  - The separation and detection of inorganic ions on microfluidic devices has
      received little attention since the 'lab-on-a-chip' concept has revolutionised
      the field of electrokinetically driven analysis. This review presents a summary
      and discussion of the published literature on inorganic analysis using
      microfluidic devices and includes sections on electromigration separation
      methods, namely isotachophoresis (ITP), capillary electrophoresis (CE), and
      hyphenated ITP-CE, together with a brief account of flow injection analysis. The
      review concludes with the authors' perspective on future directions for inorganic
      analysis on microfluidic devices.

PMID- 15565714
TI  - Separation of biomolecules using electrophoresis and nanostructures.
AB  - A large number of nanostructures have the potential to be used together with
      electrophoresis as separation media or separation additive in capillary
      electrophoresis, micellar electrokinetic chromatography, capillary
      electrochromatography, and other analytical techniques. Among those structures
      are nanotubes, nanocavities, nanowires, nanoposts, nanocones, nanospheres,
      molecular imprints, nanoparachutes (conical monodendrons), and general
      nanoparticles with random structures. This review is focused only on publications
      describing experimental works using molecular imprints, nanoposts, and
      nanospheres that are fabricated and applied for the purpose of separation media
      in electrophoresis-driven separations. The review follows an approximate
      chronological order in each section. As shown, the most popular are those
      resulting from molecular imprinting technologies. These biomimetic receptors are
      used in a great variety of fields, which includes electrophoresis, micellar
      electrokinetic chromatography, capillary electrochromatography, and other fields
      not reviewed in this work. A few examples of these other fields are, e.g., liquid
      chromatography, membranes, extractor or preconcentration techniques,
      immunosorbent assays, and sensing devices. The second topic scanned in the
      present work is the nanostructures that are used as obstacles to replace gels or
      polymers solutions in electrophoresis. Finally, the nascent field of nanospheres
      of gold and other materials as separation media is also reviewed.

PMID- 15565715
TI  - New directions of miniaturization within the biomarker research area.
AB  - An overview of the current trends within protein expression profiling is given
      where multidimensional separation of both gel and liquid phase techniques linked
      to mass spectrometry is viewed as a major route in the global proteome mapping. A
      clear trend in these biochemical developments is the effort to sequence and
      identify low-abundant protein expressions where assay miniaturization and
      integrated sample processing play a central role. Two areas of miniaturization
      within the proteomics field are addressed: (i) sample cleanup and enrichment, and
      (ii) silicon microstructure developments for protein chip microarrays.

PMID- 15565717
TI  - Expression of heterologous proteins in Pichia pastoris: a useful experimental
      tool in protein engineering and production.
AB  - The use of the methylotrophic yeast, Pichia pastoris, as a cellular host for the
      expression of recombinant proteins has become increasing popular in recent times.
      P. pastoris is easier to genetically manipulate and culture than mammalian cells
      and can be grown to high cell densities. Equally important, P. pastoris is also a
      eukaryote, and thereby provides the potential for producing soluble, correctly
      folded recombinant proteins that have undergone all the post-translational
      modifications required for functionality. Additionally, linearized foreign DNA
      can be inserted in high efficiency via homologous recombination procedures to
      generate stable cell lines whilst expression vectors can be readily prepared that
      allow multiple copies of the target protein, multimeric proteins with different
      subunit structures, or alternatively the target protein and its cognate binding
      partners, to be expressed. A further benefit of the P. pastoris system is that
      strong promoters are available to drive the expression of a foreign gene(s) of
      interest, thus enabling production of large amounts of the target protein(s) with
      relative technical ease and at a lower cost than most other eukaryotic systems.
      The purpose of this review is to summarize important developments and features of
      this expression system and, in particular, to examine from an experimental
      perspective the genetic engineering, protein chemical and molecular design
      considerations that have to be taken into account for the successful expression
      of the target recombinant protein. Included in these considerations are the
      influences of P. pastoris strain selection; the choice of expression vectors and
      promoters; procedures for the transformation and integration of the vectors into
      the P. pastoris genome; the consequences of rare codon usage and truncated
      transcripts; and techniques employed to achieve multi-copy integration numbers.
      The impact of the alcohol oxidase (AOX) pathways in terms of the mut+ and mut(s)
      phenotypes, intracellular expression and folding pathways is examined. The roles
      of pre-pro signal sequences such as the alpha mating factor (alpha-MF) and the
      Glu-Ala repeats at the kex2p cleavage site on the processing of the protein
      translate(s) have also been considered. Protocols for the generation of protein
      variants and mutants for screening for orphan cognate binding partners and the
      use of experimental platforms addressing the molecular recognition behaviour of
      recombinant proteins such as the extracellular domains of transmembrane receptors
      with their physiological ligands are also described. Finally, the palindromic
      patterns of glycosylation that can occur with these expression systems, in terms
      of the role and location of the sequon in the primary structure, the number of
      mannose units and the types of oligosaccharides incorporated as Asn- or O
      linkages and their impact on the thermostability and immunogenicity of the
      recombinant protein are considered. Procedures to prevent glycosylation through
      manipulation of cell culture conditions or via enzymatic and site-directed
      mutagenesis methods are also discussed.

PMID- 15565719
TI  - Development of an ion mobility spectrometer for use in an atmospheric pressure
      ionization ion mobility spectrometer/mass spectrometer instrument for fast
      screening analysis.
AB  - An ion mobility spectrometer that can easily be installed as an intermediate
      component between a commercial triple-quadrupole mass spectrometer and its
      original atmospheric pressure ionization (API) sources was developed. The curtain
      gas from the mass spectrometer is also used as the ion mobility spectrometer
      drift gas. The design of the ion mobility spectrometer allows reasonably fast
      installation (about 1 h), and thus the ion mobility spectrometer can be
      considered as an accessory of the mass spectrometer. The ion mobility
      spectrometer module can also be used as an independently operated device when
      equipped with a Faraday cup detector. The drift tube of the ion mobility
      spectrometer module consists of inlet, desolvation, drift, and extraction
      regions. The desolvation, drift and extraction regions are separated by ion
      gates. The inlet region has the shape of a stainless steel cup equipped with a
      small orifice. Ion mobility spectrometer drift gas is introduced through a
      curtain gas line from an original flange of the mass spectrometer. After passing
      through the drift tube, the drift gas serves as a curtain gas for the ion
      sampling orifice of the ion mobility spectrometer before entering the ion source.
      Counterflow of the drift gas improves evaporation of the solvent from the
      electrosprayed sample. Drift gas is pumped away from the ion source through the
      original exhaust orifice of the ion source. Initial characterization of the ion
      mobility spectrometer device includes determination of resolving power values for
      a selected set of test compounds, separation of a simple mixture, and comparison
      of the sensitivity of the electrospray ionization ion mobility spectrometry/mass
      spectrometry (ESI-IMS/MS) mode with that of the ESI-MS mode. A resolving power of
      80 was measured for 2,6-di-tert-butylpyridine in a 333 V/cm drift field at room
      temperature and with a 0.2 ms ion gate opening time. The resolving power was
      shown to be dependent on drift gas flow rate for all studied ion gate opening
      times. Resolving power improved as the drift gas flow increased, e.g. at a 0.5 ms
      gate opening time, a resolving power of 31 was obtained with a 0.65 L/min flow
      rate and 47 with a 1.3 L/min flow rate for tetrabutylammonium iodide. The
      measured limits of detection with ESI-MS and with ESI-IMS/MS modes were similar,
      demonstrating that signal losses in the IMS device are minimal when it is
      operated in a continuous flow mode. Based on these preliminary results, the
      IMS/MS instrument is anticipated to have potential for fast screening analysis
      that can be applied, for example, in environmental and drug analysis.

PMID- 15565720
TI  - Collision-induced dissociation of the [M-2H]2- ion of C-peptide.

PMID- 15565721
TI  - Three bits eight states photochromic recording and nondestructive readout by
      using IR light.
AB  - A photochromic polymer film containing three different diarylethene derivatives,
      that is, 1,2-bis(3,5-dimethyl-2-thienyl)perfluorocyclopentene (1), 1,2-bis(2,5
      dimethyl-3-thienyl)perfluorocyclopentene (2), and 1,2-bis(2-methyl-5-phenyl-3
      thienyl)perfluorocyclopentene (3) was prepared. Upon UV irradiation, the three
      derivatives changed to their closed-ring isomers having different colors, yellow,
      red, and blue. They showed different spectra not only in UV/Vis region but also
      in the IR spectral region. Upon irradiation with visible light of appropriate
      wavelengths, each closed-ring isomer was selectively bleached, and three bits
      eight states recording was performed. The eight states could be read out
      nondestructively by using IR light of appropriate wavenumbers.

PMID- 15565722
TI  - Solution conformation and dynamics of the ion pairs originating from the reaction
      of B(C6F5)3 with bisindenyl dimethyl zirconium complexes.
AB  - The two ion pairs [(4,7-Me(2)indenyl)(2)ZrMe](+)[MeB(C(6)F(5))(3)](-) (1 b) and
      [(indenyl)(2)ZrMe](+) [MeB(C(6)F(5))(3)](-) (2 b) have been generated in situ by
      reaction of stoichiometric B(C(6)F(5))(3) with the corresponding dimethyl
      zirconocenes. It has been shown that molecular mechanics computations, guided by
      experimental (1)H/(1)H NOE correlations, can provide information on the
      conformers present in solution. The dynamics of the ion pairs has also been
      investigated, showing the occurrence of both the processes previously
      characterized for this class of compounds, namely the B(C(6)F(5))(3) migration
      between the two methyl groups and dissociation-recombination of the whole
      [MeB(C(6)F(5))(3)](-) anion, the latter process being much faster than the first
      one (about three order of magnitude). Moreover, it has been shown that in certain
      conditions intermolecular processes can occur, which mimic the above-mentioned
      dissociative exchanges. In particular, the presence of species containing loosely
      bound [MeB(C(6)F(5))(3)](-) anion fastens the exchange of this anion, while the
      presence of free B(C(6)F(5))(3) accelerates its exchange between the two methyl
      sites.

PMID- 15565723
TI  - Coordination of iron(III) cations to beta-keto esters as studied by electrospray
      mass spectrometry: implications for iron-catalyzed Michael addition reactions.
AB  - Solutions of Fe(III) salts and beta-keto esters have been investigated by means
      of electrospray ionization mass spectrometry. The complexes formed in such
      solutions have been considered previously as active intermediates in Fe(III)
      catalyzed Michael additions. By using different Fe(III) salts with a set of beta
      keto esters, cation and anion mass spectra were analyzed and the effects of ester
      concentration, the role of the counterion, and the structure of the ester
      employed are discussed. Depending on the basicity of the ester, an increase of
      its concentration may lead to a decrease in the concentration of iron complexes
      observed in the mass spectra. Counterions with strong binding affinities to iron
      are found to capture the metal as ferrates, thereby removing the metal from the
      catalytic cycle.

PMID- 15565724
TI  - An asymmetric formal synthesis of fasicularin.
AB  - An asymmetric formal synthesis of fasicularin (1) is described. This natural
      product, isolated from the extracts of the marine invertebrate Nephteis
      fasicularis, has shown modest cytotoxicity towards Vero cells. Fasicularin is
      among only two members of the cylindricine family of natural products, along with
      lepadiformine (2), to possess a trans A-B ring junction. Key steps of this
      approach to 1 involve a siloxy-epoxide semipinacol rearrangement of 5 to 6, a B
      alkyl Suzuki-Miyaura coupling reaction by using enol trifluoromethanesulfonate 19
      and a substrate-directed hydrogenation reaction of 24. This formal synthesis also
      highlights the difficulty in the incorporation of the thiocyanate functionality
      present in 1.

PMID- 15565725
TI  - 7-Azaindolyl- and 2,2'-dipyridylamino-functionalized molecular stars with sixfold
      symmetry: self-assembly, luminescence, and coordination compounds.
AB  - Two novel star molecules functionalized with 7-azaindolyl and 2,2'-dipyridylamino
      groups have been synthesized. Both molecules possess a sixfold rotation symmetry.
      Molecule L1 is based on the hexaphenylbenzene core with the formula of hexa[p-(7
      azaindolyl)phenyl]benzene, while molecule L2 is based on the
      hexakis(biphenyl)benzene core with the formula of hexa[p-(2,2'
      dipyridylamino)biphenyl]benzene. Both compounds have been characterized by single
      crystal X-ray diffraction analyses. Molecule L1 forms extended two-dimensional
      layered structure, while L2 forms interpenetrating columnar stacks in the solid
      state, as revealed by X-ray diffraction analyses. Nanowire structures based on
      columnar stacks through self-assembly of L2 on a graphite surface were revealed
      by an STM study. Molecules L1 and L2 are capable of binding to metal ions,
      resulting in unusual structural motifs. Two Ag(I) complexes with the formulae of
      [(AgNO(3))(2)(L1)] (1) and [(AgNO(3))(3)(L1)] (2) were isolated from the
      reactions of AgNO(3) with L1. Compound 1 displays extended intermolecular pi-pi
      stacking interactions that are responsible for its extended two-dimensional
      structure in the crystal lattice. Complex 2 has a "bowl" shape and forms polar
      stacks in the crystal lattice. A Cu(II) complex with the formula of
      [{Cu(NO(3))(2)}(6)(L 2)] (3) was isolated from the reaction of Cu(NO(3))(2) with
      compound L2. The six Cu(II) ions in 3 are chelated by the 2,2'-dipyridylamino
      groups of the star ligand L2. Intermolecular Cu-O (nitrate) bonds lead to the
      formation of an extended two-dimensional coordination network of 3. Both L1 and
      L2 are blue luminescent. Their interactions with Ag(I) or Cu(II) cause drastic
      quenching of emission. In addition, the luminescence of L1 and L2 is sensitive to
      the presence of protons, which cause a reduction of emission intensity and a red
      shift of the emission energy.

PMID- 15565726
TI  - Hierarchical self-assembly of a bow-shaped molecule bearing self-complementary
      hydrogen bonding sites into extended supramolecular assemblies.
AB  - The bow-shaped molecule 1 bearing a self-complementary DAAD-ADDA (D=donor
      A=acceptor) hydrogen-bonding array generates, in hydrocarbon solvents, highly
      ordered supramolecular sheet aggregates that subsequently give rise to gels by
      formation of an entangled network. The process of hierarchical self-assembly of
      compound 1 was investigated by the concentration and temperature dependence of UV
      visible and (1)H NMR spectra, fluorescence spectra, and electron microscopy data.
      The temperature dependence of the UV-visible spectra indicates a highly
      cooperative process for the self-assembly of compound 1 in decaline. The electron
      micrograph of the decaline solution of compound 1 (1.0 mM) revealed
      supramolecular sheet aggregates forming an entangled network. The selected area
      electronic diffraction patterns of the supramolecular sheet aggregates were
      typical for single crystals, indicative of a highly ordered assembly. The results
      exemplify the generation, by hierarchical self-assembly, of highly organized
      supramolecular materials presenting novel collective properties at each level of
      organization.

PMID- 15565727
TI  - Shape-controlled synthesis of metal nanostructures: the case of silver.
AB  - The concept of shape-controlled synthesis is discussed by investigating the
      growth mechanisms for silver nanocubes, nanowires, and nanospheres produced
      through a polymer-mediated polyol process. Experimental parameters, such as the
      concentration of AgNO(3) (the precursor to silver), the molar ratio between
      poly(vinylpyrrolidone) (PVP, the capping agent) and AgNO(3), and the strength of
      chemical interaction between PVP and various crystallographic planes of silver,
      were found to determine the crystallinity of seeds (e.g., single crystal versus
      decahedral multiply twinned particles). In turn, the crystallinity of a seed and
      the extent of the PVP coverage on the seed were both instrumental in controlling
      the morphology of final product. The ability to generate silver nanostructures
      with well-defined morphologies provides a great opportunity to experimentally and
      systematically study the relationship between their properties and geometric
      shapes.

PMID- 15565728
TI  - From suspicion to action: the chemical conjunctivitis and silver nitrate
      connexion example in Brazilian hospitals.
AB  - BACKGROUND: During the 20th century, silver nitrate (SN) eye drops instillation
      to newborns had been the best prophylaxis against ophthalmia neonatorum (ON)
      caused by Neisseria gonorrheae, the most frequent cause of ocular infections
      leading to blindness. At present, this treatment has been questioned because
      there is a growing prevalence of other pathogens such as Chlamydia trachomatis,
      and SN is associated with chemical conjunctivitis (ChC). In addition, SN could
      present some conservation problems in tropical climates. Among other alternative
      drugs, 2.5% povidone-iodine has a proven efficacy, not only against Neisseria,
      but also against Chlamydia, has no conservation problems, has not been associated
      with ChC and is cheap. METHODS: The recently created Setor de Farmacovigilancia
      (SF) of the Sao Paulo State in Brazil has created a pharmacovigilance network of
      11 big public hospitals. During a periodical signal searching process, the SF
      found a cluster of 33 ChC reports from one of the network hospitals. RESULTS: The
      problem was discussed with the remaining participant hospitals and this signal
      was used as a way to strengthen the network. Thirteen months later, 622 ChC
      reports were received from six hospitals. DISCUSSION: Thus, this well-known side
      effect in the literature was highlighted as a 'real' problem in Brazil, and some
      participant hospitals began a discussion period together with the delivery and
      newborn care professionals in order to switch SN by povidone-iodine. This is an
      example of both, how a simple pharmacovigilance exercise could improve the
      implication of health professionals with their own therapeutic problems and how a
      pharmacovigilance network could be strengthened.

PMID- 15565729
TI  - New modules for the repeated internal and N-terminal epitope tagging of genes in
      Saccharomyces cerevisiae.
AB  - Epitope tagging is a powerful method for the rapid analysis of protein function.
      In Saccharomyces cerevisiae epitope tags are introduced easily into chromosomal
      loci by homologous recombination using a simple PCR-based strategy. Although
      quite a number of tools exist for C-terminal tagging as well as N-terminal
      tagging of proteins expressed by heterologous promoters, there are only very
      limited possibilities to tag proteins at the N-terminus and retain the endogenous
      expression level. Furthermore, no PCR-templates for internal tagging have been
      reported. Here we describe new modules that are suitable for both the repeated N
      terminal and internal tagging of proteins, leaving their endogenous promoters
      intact. The tags include 6xHA, 9xMyc, yEGFP, TEV-GST-6xHIS, ProtA, TEV-ProtA and
      TEV-ProtA-7xHIS in conjunction with different heterologous selection markers.

PMID- 15565730
TI  - Bayesian non-response models for categorical data from small areas: an
      application to BMD and age.
AB  - We provide a Bayesian analysis of data categorized into two levels of age
      (younger than 50 years, at least 50 years) and three levels of bone mineral
      density (normal, osteopenia, osteoporosis) for white females at least 20 years
      old in the third National Health and Nutrition Examination Survey. For the
      sample, the age of each individual is known, but some individuals did not have
      their BMD measured. We use two types of models: In the ignorable non-response
      models the propensity to respond does not depend on BMD and age of an individual,
      while in the non-ignorable non-response models it does. These are the baseline
      models which are used to derive all models for testing. Our non-ignorable non
      response models are 'close' to the ignorable non-response models, thereby
      reducing the effects of the assumptions about non-respondents that cannot be
      tested in non-response models. We have data from 35 counties, small areas, and
      therefore our models are hierarchical, a feature that allows a 'borrowing of
      strength' across the counties, and they provide a substantial reduction in
      variation. The non-ignorable non-response models are generalizations of the
      ignorable non-response models, and therefore, the non-ignorable non-response
      models allow broader inference. The joint posterior density of the parameters for
      each model is complex, and therefore, we fit each model using Markov chain Monte
      Carlo methods to obtain samples which are used to make inference about BMD and
      age. For each county we can estimate the proportion of individuals in each BMD
      and age cell of the categorical table, and we can assess the relation between BMD
      and age using the Bayes factor. A sensitivity analysis shows that there are
      differences (typically small) in inference that permits different levels of
      association between BMD and age. A simulation study shows that there is not much
      difference between the baseline ignorable and non-ignorable non-response models.

PMID- 15565731
TI  - Fast screening method for the analysis of total flavonoid content in plants and
      foodstuffs by high-performance liquid chromatography/electrospray ionization time
      of-flight mass spectrometry with polarity switching.
AB  - A liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS)
      method based on time-of-flight (TOF) MS with polarity switching and continuous
      exact mass measurement using a LockSpray ion source was developed for fast
      evaluation of the total flavonoid content in plants and foodstuffs. No
      complicated sample preparation was needed, but only a dilution of the extracts. A
      fast generic gradient elution and wide mass range acquisition was used with good
      sensitivity. The total analysis time was only 23 min. The ion chromatograms for
      flavonoid compounds were automatically extracted, and the fragmentation patterns
      obtained using positive ion mode and exact mass data for both polarities were
      used for the tentative identification of compounds. Software-based automated
      searching of molecular ions for flavonoids and their glycosides
      (xylosides/arabinosides, rhamnosides, glucosides/galactosides) from total ion
      chromatograms was used. The compounds were quantified using quercetin,
      quercitrin, rutin and kuromanine as external standards and dextromethorphan as an
      internal standard. The detection limits ranged from 0.01-0.04 microg/mL, while
      the quantitation ranges obtained were 0.2-10 microg/mL for anthocyanins and 0.2-4
      microg/mL for the other flavonoids. The accuracies within these ranges varied
      between 80-120% and precision was in the range 0-14% (relative standard
      deviation). Flavonoid contents of two medicinal plants (Hypericum perforatum and
      Rhodiola rosea), two grape red wines, two orange juices and two green teas were
      evaluated using the method, and the results obtained were in good agreement with
      those published previously.

PMID- 15565732
TI  - Rapid and selective identification of molecular species in phosphatidylcholine
      and sphingomyelin by conditional neutral loss scanning and MS3.
AB  - Analyses of molecular species of phospholipids containing choline (Ch), such as
      phosphatidylcholine (PC) and sphingomyelin (SM), are reported. Neutral loss
      scanning was applied for the selective detection of these lipids using a
      quadrupole-linear ion trap mass spectrometer. By using ammonium formate as an
      elution buffer, both PC and SM were detected as [M+HCOO]- ions in the negative
      ion mode. Upon collisional activation, the [M+HCOO]- adduct ions underwent facile
      elimination of HCO2, to yield an ion which, in turn, readily underwent
      collisional-induced dissociation (CID) to eliminate CH3 to yield an [M-CH3]- ion.
      By selecting the proper conditions for scanning for neutral loss of 60 Da
      (HCO2+CH3), SM species were identified separately from PCs. Further, by selection
      of this [M-CH3]- ion as the precursor ion, the identities of the fatty acyl
      chains of PC species can be effectively obtained by MS3 experiments. Furthermore,
      by the MS3 analyses of [M-CH3]- specifically obtained from SM molecules,
      identification of sphingosine or sphinganine derivatives and their N-acyl species
      can also be effectively obtained. This systematic analysis of PCs and SMs by
      conditional neutral loss scanning, with subsequent analyses by MS3, using a
      linear ion trap mass spectrometer in the negative ion mode, appears to be a very
      effective and sensitive method. Further, MS/MS in the positive ion mode at
      relatively low collision energy was also effective for the identification of
      positional specificities in individual molecular PC species from their lysoPC
      related fragments. The present paper deals only with qualitative identification
      of individual molecular species, and the related quantitative studies are now
      underway.

PMID- 15565733
TI  - Characterization of limonin glucoside metabolites from human prostate cell
      culture medium using high-performance liquid chromatography/electrospray
      ionization mass spectrometry and tandem mass spectrometry.
AB  - The metabolism of limonin 17-beta-D-glucopyranoside (LG) by non-cancerous (RWPE
      1) and cancerous (PC-3) human prostate epithelial cells was investigated using
      high-performance liquid chromatography/electrospray ionization mass spectrometry
      (LC/ESI-MS) with in-source fragmentation and tandem mass spectrometry (MS/MS).
      During positive ion LC/ESI-MS, LG formed an abundant sodiated species ([M+Na]+)
      while the protonated molecule was barely observable. [M+Na]+ further fragmented
      into the less abundant [LARL+H]+ and a predominantly protonated aglycone molecule
      (limonin) due to in-source fragmentation. The major metabolite, limonin A-ring
      lactone (LARL), formed an abundant protonated molecule that was fragmented into a
      protonated molecule of limonin by loss of one molecule of water. In MS/MS by
      collisionally activated dissociation (CAD), LG produced the sodiated aglycone,
      [aglycone+Na]+, while LARL fragmented into [M+H]+ of limonin and fragment ions
      resulted by further loss of water, carbon monoxide and carbon dioxide, indicating
      the presence of oxygenated-ring structures. The limits of detection of LG were
      0.4 and 20 fmol in selected-ion monitoring (SIM) and selected-reaction monitoring
      (SRM) detection, respectively.

PMID- 15565734
TI  - Automatic mass spectrometry method development for drug discovery: application in
      metabolic stability assays.
AB  - High-throughput metabolic screening has been requested routinely to keep pace
      with high-throughput organic synthesis. Liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) with a fast gradient has become the method of choice for
      the task due to its sensitivity and selectivity. We have developed an automated
      system that consists of a robotic system for in vitro incubation and a
      commercially available software package for automatic MS/MS method development. A
      short, generic LC gradient and MS conditions that are applicable to most
      compounds have been developed to minimize the method development time and data
      analysis. This system has been used to support a number of in vitro screening
      assays in early drug discovery phase including microsomal stability and protein
      binding.

PMID- 15565735
TI  - Statistical analysis of current status data with informative observation times.
AB  - Current status data arise when each study subject is observed only once and the
      survival time of interest is known only to be either less or greater than the
      observation time. Such data often occur in, for example, cross-sectional studies,
      demographical investigations and tumorigenicity experiments and several semi
      parametric and non-parametric methods for their analysis have been proposed.
      However, most of these methods deal only with the situation where observation
      time is independent of the underlying survival time completely or given
      covariates. This paper discusses regression analysis of current status data when
      the observation time may be related to the underlying survival time and inference
      procedures are presented for estimation of regression parameters under the
      additive hazards regression model. The procedures can be easily implemented and
      are applied to two motivating examples.

PMID- 15565736
TI  - Interval estimation of the proportion ratio under multiple matching.
AB  - The discussions on interval estimation of the proportion ratio (PR) of responses
      or the relative risk (RR) of a disease for multiple matching have been generally
      focused on the odds ratio (OR) based on the assumption that the latter can
      approximate the former well. When the underlying proportion of outcomes is not
      rare, however, the results for the OR would be inadequate for use if the PR or RR
      was the parameter of our interest. In this paper, we develop five asymptotic
      interval estimators of the common PR (or RR) for multiple matching. To evaluate
      and compare the finite sample performance of these estimators, we apply Monte
      Carlo simulation to calculate the coverage probability and the average length of
      the resulting confidence intervals in a variety of situations. We note that when
      we have a constant number of matching, the interval estimator using the
      logarithmic transformation of the Mantel-Haenszel estimator, the interval
      estimator derived from the quadratic inequality given in this paper, and the
      interval estimator using the logarithmic transformation of the ratio estimator
      can consistently perform well. When the number of matching varies between matched
      sets, we find that the interval estimator using the logarithmic transformation of
      the ratio estimator is probably the best among the five interval estimators
      considered here in the case of a small number (=20) of matched sets. To
      illustrate the use of these interval estimators, we employ the data studying the
      supplemental ascorbate in the supportive treatment of terminal cancer patients.

PMID- 15565737
TI  - Supplementary analysis of probabilities at the termination of a group sequential
      phase II trial.
AB  - We consider estimation of various probabilities after termination of a group
      sequential phase II trial. A motivating example is that the stopping rule of a
      phase II oncologic trial is determined solely based on response to a drug
      treatment, and at the end of the trial estimating the rate of toxicity and
      response is desirable. The conventional maximum likelihood estimator (sample
      proportion) of a probability is shown to be biased, and two alternative
      estimators are proposed to correct for bias, a bias-reduced estimator obtained by
      using Whitehead's bias-adjusted approach, and an unbiased estimator from the Rao
      Blackwell method of conditioning. All three estimation procedures are shown to
      have certain invariance property in bias. Moreover, estimators of a probability
      and their bias and precision can be evaluated through the observed response rate
      and the stage at which the trial stops, thus avoiding extensive computation.

PMID- 15565738
TI  - Two-part statistics with paired data.
AB  - In epidemiology, we often study data from a mixed distribution, i.e. with a clump
      of observations at zero and positive continuous data. Lachenbruch developed
      statistics for this kind of data for independent samples. These tests are the sum
      of one test for equality of proportions of zero values and one conditional test
      for the continuous distribution. This paper concerns the adaptation of these
      tests to paired samples. Like Lachenbruch, we developed two statistics, which
      tend to a two-degree-of-freedom chi2 distribution. These two-part statistics are
      the sum of McNemar's test for testing the equality of proportions of zero values,
      and the Wilcoxon signed-rank test or the paired Student's test for testing the
      equality of the distribution of positive values. We studied the behaviour of
      these tests for various proportions of zeros, and mean values of the continuous
      distribution. All tests are efficient when the smaller proportion of zero values
      corresponds to the population with the larger mean. In all other situations, the
      two-part statistics are superior to the others. These methods are applied to a
      matched case-control study of lower limb venous insufficiency.

PMID- 15565739
TI  - Strategies adopted and lessons learnt during the severe acute respiratory
      syndrome crisis in Singapore.
AB  - In Singapore, the military was actively involved in the containment of the
      outbreak of severe acute respiratory syndrome (SARS) last year. The outbreak
      started in February 2003 with three Singapore travellers to Hong Kong. At that
      time, nothing was known about the aetiological agent of the atypical pneumonia
      that was termed SARS. Unfortunately one of the travellers was a super-spreader,
      defined as a person with high efficiency for virus transmission, and was
      responsible for the expansion of the national outbreak. Not only was the
      Singapore military involved in contact tracing of personnel and enforcement of
      home quarantine, military-affiliated research institutes were also involved in
      providing diagnostic support. This review reconstructs the events that took place
      during the SARS outbreak, focusing on the special support arising from
      complementing the military-affiliated laboratory with the public health
      laboratory. A description of the diagnostic findings is provided in chronological
      order. The review ends with lessons Singapore learnt from the SARS crisis,
      stressing the importance of national preparedness for future outbreaks.

PMID- 15565740
TI  - Bayesian analysis of misclassified binary data from a matched case-control study
      with a validation sub-study.
AB  - Bayesian methods are proposed for analysing matched case-control studies in which
      a binary exposure variable is sometimes measured with error, but whose correct
      values have been validated for a random sample of the matched case-control sets.
      Three models are considered. Model 1 makes few assumptions other than randomness
      and independence between matched sets, while Models 2 and 3 are logistic models,
      with Model 3 making additional distributional assumptions about the variation
      between matched sets. With Models 1 and 2 the data are examined in two stages.
      The first stage analyses data from the validation sample and is easy to perform;
      the second stage analyses the main body of data and requires MCMC methods. All
      relevant information is transferred between the stages by using the posterior
      distributions from the first stage as the prior distributions for the second
      stage. With Model 3, a hierarchical structure is used to model the relationship
      between the exposure probabilities of the matched sets, which gives the potential
      to extract more information from the data. All the methods that are proposed are
      generalized to studies in which there is more than one control for each case. The
      Bayesian methods and a maximum likelihood method are applied to a data set for
      which the exposure of every patient was measured using both an imperfect measure
      that is subject to misclassification, and a much better measure whose
      classifications may be treated as correct. To test methods, the latter
      information was suppressed for all but a random sample of matched sets.

PMID- 15565741
TI  - Receptor-assisted combinatorial chemistry: thermodynamics and kinetics in drug
      discovery.
AB  - Current drug discovery using combinatorial chemistry involves synthesis followed
      by screening, but emerging methods involve receptor-assistance to combine these
      steps. Adding stoichiometric amounts of receptor during library synthesis alters
      the kinetics or thermodynamics of the synthesis in a way that identifies the best
      binding library members. Three main methods have emerged thus far in receptor
      assisted combinatorial chemistry: dynamic combinatorial libraries, receptor
      accelerated synthesis, and a new method, pseudo-dynamic libraries. Pseudo-dynamic
      libraries apply both thermodynamics and kinetics to amplify library members to
      easily observable levels, and attain selectivity heretofore unseen in receptor
      assisted systems.

PMID- 15565742
TI  - Optical sensors based on hybrid DNA/conjugated polymer complexes.
AB  - Single-stranded DNA (ss-DNA) can specifically bind to various targets, including
      a complementary ss-DNA, ions, proteins, drugs, and so forth. When binding takes
      place, the oligonucleotide probe often undergoes a conformational transition.
      This conformational change of the negatively charged ss-DNA can be detected by
      using a water-soluble, cationic polythiophene derivative, which transduces the
      complex formation into an optical (colorimetric or fluorometric) signal without
      any labeling of the probe or the target. This simple and rapid methodology has
      enabled the specific and sensitive detection of nucleic acids and human thrombin.
      This new biophotonic tool can easily be applied to the detection of various other
      biomolecules and is also useful in the high-throughput screening of new drugs.

PMID- 15565743
TI  - Characterization of the eicosapentaenoic acid biosynthesis gene cluster from
      Shewanella sp. strain SCRC-2738.
AB  - The 38 kb eicosapentaenoic acid (EPA) biosynthesis gene cluster of Shewanella sp.
      strain SCRC-2738 was cloned into the cosmid vector (pEPA). A 27 kb nucleotide
      sequence of the XhoI to SpeI region of pEPA showed EPA production (6.3%) in E.
      coli JM109. Among the nine open reading frames (ORFs) in this sequence, only five
      (ORFs 2 and 5-8) were essential for EPA production. High levels of production
      (16%-22%) were found in E. coli JM109 transformed with a multicopy pNEB vector
      carrying only the five essential ORFs and in that transformed with a pNEB vector
      that integrated ORFs 3, 5, 6, 7 and 8, and vector pSTV28 that integrated the ORF2
      encoding phosphopantetheinyl transferase (PPTase). Thus, production of EPA
      appears to be regulated by the presence of all the biosynthesis gene products and
      by the ratio of PPTase to the other gene products. The temperature -EPA
      production relationship in E. coli strain DH5alpha varied between constructs,
      suggesting that it is controlled not only by EPA biosynthesis enzymes but also by
      other factors in vivo. There was a strict upper temperature limit for EPA
      biosynthesis: no EPA was synthesized at 30 degrees C in E. coli transformants
      carrying any gene construct for EPA biosynthesis.

PMID- 15565744
TI  - Pakistan:a cirrhotic state?

PMID- 15565745
TI  - A rational basis for race.

PMID- 15565746
TI  - Human Crimean-Congo hemorrhagic fever, Senegal.

PMID- 15565747
TI  - Toremifene citrate (Fareston).

PMID- 15565748
TI  - [Guideline of respiratory function tests--spirometry, flow-volume curve,
      diffusion capacity of the lung].

PMID- 15565749
TI  - Medicaid program; time limitation on recordkeeping requirements under the drug
      rebate program. Final rule.
AB  - This final rule finalizes 10-year recordkeeping requirements for drug
      manufacturers under the Medicaid drug rebate program. Manufacturers must retain
      records for 10 years from the date the manufacturer reports data to us for a
      rebate period. This final rule also finalizes the requirement that manufacturers
      must retain records beyond the 10-year period if the records are known by the
      manufacturer to be the subject of an audit or a government investigation.
      Furthermore, this final rule responds to public comments on the January 6, 2004
      interim final rule with comment period and the proposed rule pertaining to the 10
      year recordkeeping requirements, respectively.

PMID- 15565750
TI  - Medicare program; expedited determination procedures for provider service
      terminations. Final rule with comment period.
AB  - This final rule with comment period responds to comments on one discrete aspect
      of the proposed rule published in the Federal Register on November 15, 2002. The
      portion of that proposed rule addressed here involves the expedited determination
      and reconsideration procedures available to beneficiaries when a provider informs
      them of a decision that Medicare coverage of their provider services is about to
      end.

PMID- 15565751
TI  - Ximelagatran in prevention of cardiovascular events.
AB  - Ximelagatran (Exanta (R) is the first oral anticoagulant in a new class of drugs
      called direct thrombin inhibitors. Two studies suggest that ximelagatran is at
      least as effective as warfarin in preventing stroke in high risk patients with
      atrial fibrillation. Ximelagatran may also reduce the rate of major
      cardiovascular events after a myocardial infarction, compared to placebo.
      Ximelagatran does not require dose adjustments or routine blood monitoring. As
      with warfarin, bleeding risks increase with higher doses of ximelagatran. There
      is, however, no specific antidote to help manage bleeding. The safety of
      ximelagatran will not be fully known without further evaluation and surveillance
      for potential liver toxicity and drug interactions.

PMID- 15565752
TI  - RNA fingerprinting of microbial community in the rhizosphere soil of grain
      legumes.
AB  - Microbial structural and expression profiles of the rhizospheres of three
      legumes, faba beans, peas and white lupin, were compared by RNA-arbitrarily
      primed PCR technique. Two different primers, M13 reverse and 10-mer primers, were
      used in the amplification and products resolved on non-denaturing polyacrylamide
      gel. With both DNA and RNA profiles Lupinus and Pisum rhizospheres were more
      similar to each other than to Vicia rhizosphere. The RAP-PCR products were also
      dot blotted and probed for bacterial peptidase transcripts. Plant-dependent
      rhizosphere effect was evident by the marked absence of transcripts for bacterial
      neutral metallopeptidase in Lupinus rhizosphere. The results of dot blot were
      further confirmed by RT-PCR for the expression of bacterial neutral
      metallopeptidase in the three rhizospheres.

PMID- 15565753
TI  - Re: Transportal intravariceal sclerotherapy with N-butyl-2-cyanoacrylate for
      gastric varices.

PMID- 15565754
TI  - Toilet training.

PMID- 15565755
TI  - Hospital infections.

PMID- 15565756
TI  - An audit of the process of developing the Health Improvement Programme into
      Strategic and Financial Framework in two health authorities.
AB  - Health Improvement Programmes (HImPs) are a means of documenting the health needs
      of a population and are intended to be translated into commissioning decisions by
      the Strategic and Financial Framework (SaFF). This paper examines some major
      influences on the process of translating the HImP into the SaFF. The Directors of
      Public Health in two Health Authorities were concerned that the development of
      the SaFF did not always represent a clear progression from the HImP. An audit to
      pinpoint where commissioning decisions did not match the identified health
      improvement needs in two Health Authorities was carried out between November 2000
      and February 2001. The overall findings confirmed that needs identified in the
      HImPs were not fully reflected in the service provision described in the final
      SaFFs. The audit provided evidence that was useful in identifying major issues
      and influences that facilitated or hindered the development of the SaFF from the
      HImP. Some of the ways in which HImP priorities disappeared from the SaFF and non
      HImP priorities appeared in it were also distinguished. The conclusion is that a
      clear, criterion-based process should enable health and social care communities
      and Primary Care Trusts to develop a more responsible commissioning process in
      future, and specific recommendations to that effect are made.

PMID- 15565757
TI  - Microsystems, macrosystems, and kernicterus.

PMID- 15565758
TI  - Barriers to first-week follow-up of newborns: findings from parent and clinician
      focus groups.
AB  - BACKGROUND: Monitoring newborns within the first week is critical to assess the
      adequacy of feeding and weight gain and to identify instances of
      hyperbilirubinemia. As systems of maternal and newborn care have become
      increasingly fragmented, infants are at increased risk of poor outcomes because
      of poor follow-up. Structured focus groups were conducted in June--July 2001 to
      provide information about the barriers to timely newborn follow-up and strategies
      to address them. METHODS: One focus group for physicians and one for nurses were
      held at the Henry Ford Health System, Detroit, and two focus groups of parents
      were recruited by Blue Cross Blue Shield of Texas, Dallas. RESULTS: Barriers were
      identified in communication and information, systems and processes of care, and
      parental knowledge and education. Concerns raised by clinicians and parents were
      consistent and complementary. Some organizations have begun implementing some of
      the suggested strategies to achieve timely follow-up. DISCUSSION: Implementing
      the AAP guideline and improving safe care in the first week of newborn life will
      require attention to linkages and transitions between these various microsystems.

PMID- 15565759
TI  - How to design computerized alerts to safe prescribing practices.
AB  - BACKGROUND: Medication errors and preventable adverse drug events are common, and
      about half of medication errors occur during medication ordering. This study was
      designed to develop and evaluate medication safety alerts and processes for
      educating prescribers about the alerts. METHODS: At Kaiser Permanente Northwest,
      a group-model health maintenance organization where prescribers have used
      computerized order entry since 1996, qualitative interviews were conducted with
      20 primary care prescribers. RESULTS: Prescribers considered alerts helpful for
      providing prescribing and preventive health information. More than half the
      interviewees stated that it would be unwise to let clinicians control or avoid
      safety alerts. Common frustrations were (1) being delayed by the alert, (2)
      having difficulty interpreting the alert, and (3) receiving the same alert
      repeatedly. Most prescribers preferred small-group educational sessions tied to
      existing meetings and having local physicians conduct education sessions.
      DISCUSSION: The findings were used to design a strategy for introducing and
      promoting the interventions, modifying the alert text and tools, and focusing the
      education on how clinicians could use the alerts effectively.

PMID- 15565760
TI  - Assessing return on investment of defined-population disease management
      interventions.
AB  - BACKGROUND: Strategies to reduce health expenditures through the improvement of
      health and quality of care are in high demand. A group of experts formed a
      nonpartisan, independent work group, under the sponsorship of the National
      Managed Health Care Congress. Its goal was to establish a list of easy-to
      understand, actionable, and usable recommendations to enable disease management
      program advocates to conduct basic-level evaluations. RECOMMENDATIONS: The work
      group made recommendations concerning identification of reference and
      intervention population, population definitions, quantitative methods and data
      quality, confounding and bias, and stakeholder agreements/contracting. CASE
      STUDY: A case study was created to quantitatively illustrate some of the major
      issues raised by the work group. Five typical errors were simulated by applying
      different rules to the intervention population than to the reference population:
      differential inclusion (high versus low risk), differential exclusion (high
      versus low risk) and differential claims run-out. Compared with the true impact,
      four of the five errors resulted in a bias toward "intervention effect," while
      one (differential inclusion of high-risk patients) was biased against the
      "intervention effect." The direction and magnitude of the bias in natural
      settings will not necessarily follow this pattern.

PMID- 15565761
TI  - Using variance analysis to detect hazards in a bar-code-assisted medication
      preparation process.
AB  - BACKGROUND: Medication errors have received significant attention, with studies
      pinpointing problems in the physician ordering, pharmacy dispensing, and nurse
      administering processes. Yet, the nursing process for preparing medications,
      which typically occurs in a medication room on the unit, has not received much
      attention. This process is deceptively complex, and without proper design, it
      could break down at numerous points. HUMAN FACTORS ENGINEERING ANALYSIS:
      Prospective hazard analysis methods allow the detection of potential hazards
      during the planning, assessment, and design phases of a process or technology. A
      specific technique-variance analysis-is used within one type of prospective
      hazard analysis, the sociotechnical systems analysis (STSA). STSA provides
      guidance to (1) analyze existing or planned systems to understand the social,
      technical, and environmental system components; (2) collect and analyze the
      system data; and (3) use the analysis to design or redesign the system.
      DISCUSSION: The STSA variance analysis is an additional tool that health care
      clinicians, administrators, and risk managers can use to proactively identify
      hazards for control. Although this larger analysis is more time consuming, it
      forces the analysts to conduct a true systems analysis before implementing
      technical, social, environmental, or organizational changes.

PMID- 15565762
TI  - Self-management support in a web-based medical record: a pilot randomized
      controlled trial.
AB  - Physicians were much less likely than other primary care team members to use a
      Web-based application to counsel patients with diabetes about behavior change.

PMID- 15565763
TI  - Fixing broken bones and broken homes: domestic violence as a patient safety
      issue.
AB  - BACKGROUND: Domestic violence (DV) is a significant problem in terms of both
      patient harm and cost. To better address this problem, the diagnosis and
      treatment of DV are considered within the emerging model of patient safety and
      medical error reduction. The case of a female patient who presents in the
      clinical setting following an incident of DV shows how medical errors can be
      analyzed as they are in medical cases not involving DV, such as when a person
      with abdominal pain is sent away from the emergency department with instructions
      to take an acid reducer and later suffers a burst appendix. ROOT CAUSE ANALYSIS:
      A number of factors inhibit the correct diagnosis and treatment of DV victims
      seeking additional treatment. Physicians often fail to screen for DV, misidentify
      symptoms, or deny the possibility of underlying DV, and patients often hide the
      symptoms and refuse to admit the problem. However, human factor errors related to
      knowledge, cultural norms, and individual biases; organizational factors,
      including lack of training and reimbursement; and technology factors related to
      information accessibility appear to play significant roles. CONCLUSION: Failure
      to diagnose or adequately address DV can be interpreted as medical errors.
      Addressing DV requires a systemic response, which might begin with integrating
      education and training about DV into the clinical setting, ensuring the use of
      existing screening tools, and providing adequate and appropriate reimbursement
      levels.

PMID- 15565764
TI  - A general framework for learning rules from data.
AB  - With the aim of getting understandable symbolic rules to explain a given
      phenomenon, we split the task of learning these rules from sensory data in two
      phases: a multilayer perceptron maps features into propositional variables and a
      set of subsequent layers operated by a PAC-like algorithm learns Boolean
      expressions on these variables. The special features of this procedure are that:
      i) the neural network is trained to produce a Boolean output having the principal
      task of discriminating between classes of inputs; ii) the symbolic part is
      directed to compute rules within a family that is not known a priori; iii) the
      welding point between the two learning systems is represented by a feedback based
      on a suitability evaluation of the computed rules. The procedure we propose is
      based on a computational learning paradigm set up recently in some papers in the
      fields of theoretical computer science, artificial intelligence and cognitive
      systems. The present article focuses on information management aspects of the
      procedure. We deal with the lack of prior information about the rules through
      learning strategies that affect both the meaning of the variables and the
      description length of the rules into which they combine. The paper uses the task
      of learning to formally discriminate among several emotional states as both a
      working example and a test bench for a comparison with previous symbolic and
      subsymbolic methods in the field.

PMID- 15565765
TI  - Feedforward sigmoidal networks--equicontinuity and fault-tolerance properties.
AB  - Sigmoidal feedforward artificial neural networks (FFANNs) have been established
      to be universal approximators of continuous functions. The universal
      approximation results are summarized to identify the function sets represented by
      the sigmoidal FFANNs with the universal approximation properties. The
      equicontinuous properties of the identified sets is analyzed. The equicontinuous
      property is related to the fault tolerance of the sigmoidal FFANNs. The generally
      used arbitrary weight sigmoidal FFANNs are shown to be nonequicontinuous sets. A
      class of bounded weight sigmoidal FFANNs is established to be equicontinuous. The
      fault-tolerance behavior of the networks is analyzed and error bounds for the
      induced errors established.

PMID- 15565766
TI  - Context-dependent neural nets--structures and learning.
AB  - A novel approach toward neural networks modeling is presented in the paper. It is
      unique in the fact that allows nets' weights to change according to changes of
      some environmental factors even after completing the learning process. The models
      of context-dependent (cd) neuron, one- and multilayer feedforward net are
      presented, with basic learning algorithms and examples of functioning. The Vapnik
      Chervonenkis (VC) dimension of a cd neuron is derived, as well as VC dimension of
      multilayer feedforward nets. Cd nets' properties are discussed and compared with
      the properties of traditional nets. Possibilities of applications to
      classification and control problems are also outlined and an example presented.

PMID- 15565767
TI  - Novel direct and self-regulating approaches to determine optimum growing multi
      experts network structure.
AB  - This paper presents two novel approaches to determine optimum growing multi
      experts network (GMN) structure. The first method called direct method deals with
      expertise domain and levels in connection with local experts. The growing neural
      gas (GNG) algorithm is used to cluster the local experts. The concept of error
      distribution is used to apportion error among the local experts. After reaching
      the specified size of the network, redundant experts removal algorithm is invoked
      to prune the size of the network based on the ranking of the experts. However,
      GMN is not ergonomic due to too many network control parameters. Therefore, a
      self-regulating GMN (SGMN) algorithm is proposed. SGMN adopts self-adaptive
      learning rates for gradient-descent learning rules. In addition, SGMN adopts a
      more rigorous clustering method called fully self-organized simplified adaptive
      resonance theory in a modified form. Experimental results show SGMN obtains
      comparative or even better performance than GMN in four benchmark examples, with
      reduced sensitivity to learning parameters setting. Moreover, both GMN and SGMN
      outperform the other neural networks and statistical models. The efficacy of SGMN
      is further justified in three industrial applications and a control problem. It
      provides consistent results besides holding out a profound potential and promise
      for building a novel type of nonlinear model consisting of several local linear
      models.

PMID- 15565768
TI  - Contextual processing of structured data by recursive cascade correlation.
AB  - This paper propose a first approach to deal with contextual information in
      structured domains by recursive neural networks. The proposed model, i.e.,
      contextual recursive cascade correlation (CRCC), a generalization of the
      recursive cascade correlation (RCC) model, is able to partially remove the
      causality assumption by exploiting contextual information stored in frozen units.
      We formally characterize the properties of CRCC showing that it is able to
      compute contextual transductions and also some causal supersource transductions
      that RCC cannot compute. Experimental results on controlled sequences and on a
      real-world task involving chemical structures confirm the computational
      limitations of RCC, while assessing the efficiency and efficacy of CRCC in
      dealing both with pure causal and contextual prediction tasks. Moreover, results
      obtained for the real-world task show the superiority of the proposed approach
      versus RCC when exploring a task for which it is not known whether the structural
      causality assumption holds.

PMID- 15565769
TI  - Magnified gradient function with deterministic weight modification in adaptive
      learning.
AB  - This paper presents two novel approaches, backpropagation (BP) with magnified
      gradient function (MGFPROP) and deterministic weight modification (DWM), to speed
      up the convergence rate and improve the global convergence capability of the
      standard BP learning algorithm. The purpose of MGFPROP is to increase the
      convergence rate by magnifying the gradient function of the activation function,
      while the main objective of DWM is to reduce the system error by changing the
      weights of a multilayered feedforward neural network in a deterministic way.
      Simulation results show that the performance of the above two approaches is
      better than BP and other modified BP algorithms for a number of learning
      problems. Moreover, the integration of the above two approaches forming a new
      algorithm called MDPROP, can further improve the performance of MGFPROP and DWM.
      From our simulation results, the MDPROP algorithm always outperforms BP and other
      modified BP algorithms in terms of convergence rate and global convergence
      capability.

PMID- 15565770
TI  - Hidden space support vector machines.
AB  - Hidden space support vector machines (HSSVMs) are presented in this paper. The
      input patterns are mapped into a high-dimensional hidden space by a set of hidden
      nonlinear functions and then the structural risk is introduced into the hidden
      space to construct HSSVMs. Moreover, the conditions for the nonlinear kernel
      function in HSSVMs are more relaxed, and even differentiability is not required.
      Compared with support vector machines (SVMs), HSSVMs can adopt more kinds of
      kernel functions because the positive definite property of the kernel function is
      not a necessary condition. The performance of HSSVMs for pattern recognition and
      regression estimation is also analyzed. Experiments on artificial and real-world
      domains confirm the feasibility and the validity of our algorithms.

PMID- 15565771
TI  - Encoding nondeterministic fuzzy tree automata into recursive neural networks.
AB  - Fuzzy neural systems have been a subject of great interest in the last few years,
      due to their abilities to facilitate the exchange of information between symbolic
      and subsymbolic domains. However, the models in the literature are not able to
      deal with structured organization of information, that is typically required by
      symbolic processing. In many application domains, the patterns are not only
      structured, but a fuzziness degree is attached to each subsymbolic pattern
      primitive. The purpose of this paper is to show how recursive neural networks,
      properly conceived for dealing with structured information, can represent
      nondeterministic fuzzy frontier-to-root tree automata. Whereas available prior
      knowledge expressed in terms of fuzzy state transition rules are injected into a
      recursive network, unknown rules are supposed to be filled in by data-driven
      learning. We also prove the stability of the encoding algorithm, extending
      previous results on the injection of fuzzy finite-state dynamics in high-order
      recurrent networks.

PMID- 15565772
TI  - Reproducing chaos by variable structure recurrent neural networks.
AB  - In this paper, we present a new approach for chaos reproduction using variable
      structure recurrent neural networks (VSRNN). A neural network identifier is
      designed, with a variable structure that will change according to its output
      performance as compared to the given orbits of an unknown chaotic systems. A
      tradeoff between identification errors and computational complexity is discussed.

PMID- 15565773
TI  - A hopfield network learning method for bipartite subgraph problem.
AB  - In this paper, we present a gradient ascent learning method of the Hopfield
      neural network for bipartite subgraph problem. The method is intended to provide
      a near-optimum parallel algorithm for solving the bipartite subgraph problem. To
      do this we use the Hopfield neural network to get a near-maximum bipartite
      subgraph, and increase the energy by modifying weights in a gradient ascent
      direction of the energy to help the network escape from the state of the near
      maximum bipartite subgraph to the state of the maximum bipartite subgraph or
      better one. A large number of instances are simulated to verify the proposed
      method with the simulation results showing that the solution quality is superior
      to that of best existing parallel algorithm. We also test the learning method on
      total coloring problem. The simulation results show that our method finds optimal
      solution in every test graph.

PMID- 15565774
TI  - Heterogeneous fuzzy logic networks: fundamentals and development studies.
AB  - The recent trend in the development of neurofuzzy systems has profoundly
      emphasized the importance of synergy between the fundamentals of fuzzy sets and
      neural networks. The resulting frameworks of the neurofuzzy systems took
      advantage of an array of learning mechanisms primarily originating within the
      theory of neurocomputing and the use of fuzzy models (predominantly rule-based
      systems) being well established in the realm of fuzzy sets. Ideally, one can
      anticipate that neurofuzzy systems should fully exploit the linkages between
      these two technologies while strongly preserving their evident identities
      (plasticity or learning abilities to be shared by the transparency and full
      interpretability of the resulting neurofuzzy constructs). Interestingly, this
      synergy still becomes a target yet to be satisfied. This study is an attempt to
      address the fundamental interpretability challenge of neurofuzzy systems. Our
      underlying conjecture is that the transparency of any neurofuzzy system links
      directly with the logic fabric of the system so the logic fundamentals of the
      underlying architecture become of primordial relevance. Having this in mind the
      development of neurofuzzy models hinges on a collection of logic driven
      processing units named here fuzzy (logic) neurons. These are conceptually simple
      logic-oriented elements that come with a well-defined semantics and plasticity.
      Owing to their diversity, such neurons form essential building blocks of the
      networks. The study revisits the existing categories of logic neurons, provides
      with their taxonomy, helps understand their functional features and sheds light
      on their behavior when being treated as computational components of any
      neurofuzzy architecture. The two main categories of aggregative and reference
      neurons are deeply rooted in the fundamental operations encountered in the
      technology of fuzzy sets (including logic operations, linguistic modifiers, and
      logic reference operations). The developed heterogeneous networks come with a
      well-defined semantics and high interpretability (which directly translates into
      the rule-based representation of the networks). As the network takes advantage of
      various logic neurons, this imposes an immediate requirement of structural
      optimization, which in this study is addressed by utilizing various mechanisms of
      genetic optimization (genetic algorithms). We discuss the development of the
      networks, elaborate on the interpretation aspects and include a number of
      illustrative numeric examples.

PMID- 15565775
TI  - Robust redesign of a neural network controller in the presence of unmodeled
      dynamics.
AB  - This paper presents a neural network control redesign, which achieves robust
      stabilization in the presence of unmodeled dynamics restricted to be input to
      output practically stable (IOpS), without requiring any prior knowledge on any
      bounding function. Moreover, the state of the unmodeled dynamics is permitted to
      go unbounded provided that the nominal system state and/or the control input also
      go unbounded. The neural network controller is equipped with a resetting strategy
      to deal with the problem of possible division by zero, which may appear since we
      consider unknown input vector fields with unknown signs. The uniform ultimate
      boundedness of the system output to an arbitrarily small set, plus the
      boundedness of all other signals in the closed-loop is guaranteed.

PMID- 15565776
TI  - Adaptive hybrid control for linear piezoelectric ceramic motor drive using
      diagonal recurrent CMAC network.
AB  - This paper presents an adaptive hybrid control system using a diagonal recurrent
      cerebellar-model-articulation-computer (DRCMAC) network to control a linear
      piezoelectric ceramic motor (LPCM) driven by a two-inductance two-capacitance
      (LLCC) resonant inverter. Since the dynamic characteristics and motor parameters
      of the LPCM are highly nonlinear and time varying, an adaptive hybrid control
      system is therefore designed based on a hypothetical dynamic model to achieve
      high-precision position control. The architecture of DRCMAC network is a modified
      model of a cerebellar-model-articulation-computer (CMAC) network to attain a
      small number of receptive-fields. The novel idea of this study is that it employs
      the concept of diagonal recurrent neural network (DRNN) in order to capture the
      system dynamics and convert the static CMAC into a dynamic one. This adaptive
      hybrid control system is composed of two parts. One is a DRCMAC network
      controller that is used to mimic a conventional computed torque control law due
      to unknown system dynamics, and the other is a compensated controller with bound
      estimation algorithm that is utilized to recover the residual approximation error
      for guaranteeing the stable characteristic. The effectiveness of the proposed
      driving circuit and control system is verified with hardware experiments under
      the occurrence of uncertainties. In addition, the advantages of the proposed
      control scheme are indicated in comparison with a traditional integral
      proportional (IP) position control system.

PMID- 15565777
TI  - An adaptive Hinfinity controller design for bank-to-turn missiles using ridge
      Gaussian neural networks.
AB  - A new autopilot design for bank-to-turn (BTT) missiles is presented. In the
      design of autopilot, a ridge Gaussian neural network with local learning
      capability and fewer tuning parameters than Gaussian neural networks is proposed
      to model the controlled nonlinear systems. We prove that the proposed ridge
      Gaussian neural network, which can be a universal approximator, equals the
      expansions of rotated and scaled Gaussian functions. Although ridge Gaussian
      neural networks can approximate the nonlinear and complex systems accurately, the
      small approximation errors may affect the tracking performance significantly.
      Therefore, by employing the Hinfinity control theory, it is easy to attenuate the
      effects of the approximation errors of the ridge Gaussian neural networks to a
      prescribed level. Computer simulation results confirm the effectiveness of the
      proposed ridge Gaussian neural networks-based autopilot with Hinfinity
      stabilization.

PMID- 15565778
TI  - The pre-image problem in kernel methods.
AB  - In this paper, we address the problem of finding the pre-image of a feature
      vector in the feature space induced by a kernel. This is of central importance in
      some kernel applications, such as on using kernel principal component analysis
      (PCA) for image denoising. Unlike the traditional method which relies on
      nonlinear optimization, our proposed method directly finds the location of the
      pre-image based on distance constraints in the feature space. It is noniterative,
      involves only linear algebra and does not suffer from numerical instability or
      local minimum problems. Evaluations on performing kernel PCA and kernel
      clustering on the USPS data set show much improved performance.

PMID- 15565779
TI  - Adaptive stochastic resonance in noisy neurons based on mutual information.
AB  - Noise can improve how memoryless neurons process signals and maximize their
      throughput information. Such favorable use of noise is the so-called "stochastic
      resonance" or SR effect at the level of threshold neurons and continuous neurons.
      This paper presents theoretical and simulation evidence that 1) lone noisy
      threshold and continuous neurons exhibit the SR effect in terms of the mutual
      information between random input and output sequences, 2) a new statistically
      robust learning law can find this entropy-optimal noise level, and 3) the
      adaptive SR effect is robust against highly impulsive noise with infinite
      variance. Histograms estimate the relevant probability density functions at each
      learning iteration. A theorem shows that almost all noise probability density
      functions produce some SR effect in threshold neurons even if the noise is
      impulsive and has infinite variance. The optimal noise level in threshold neurons
      also behaves nonlinearly as the input signal amplitude increases. Simulations
      further show that the SR effect persists for several sigmoidal neurons and for
      Gaussian radial-basis-function neurons.

PMID- 15565780
TI  - A neural network learning for adaptively extracting cross-correlation features
      between two high-dimensional data streams.
AB  - This paper proposes a novel cross-correlation neural network (CNN) model for
      finding the principal singular subspace of a cross-correlation matrix between two
      high-dimensional data streams. We introduce a novel nonquadratic criterion (NQC)
      for searching the optimum weights of two linear neural networks (LNN). The NQC
      exhibits a single global minimum attained if and only if the weight matrices of
      the left and right neural networks span the left and right principal singular
      subspace of a cross-correlation matrix, respectively. The other stationary points
      of the NQC are (unstable) saddle points. We develop an adaptive algorithm based
      on the NQC for tracking the principal singular subspace of a cross-correlation
      matrix between two high-dimensional vector sequences. The NQC algorithm provides
      a fast online learning of the optimum weights for two LNN. The global asymptotic
      stability of the NQC algorithm is analyzed. The NQC algorithm has several key
      advantages such as faster convergence, which is illustrated through simulations.

PMID- 15565781
TI  - Fusing images with different focuses using support vector machines.
AB  - Many vision-related processing tasks, such as edge detection, image segmentation
      and stereo matching, can be performed more easily when all objects in the scene
      are in good focus. However, in practice, this may not be always feasible as
      optical lenses, especially those with long focal lengths, only have a limited
      depth of field. One common approach to recover an everywhere-in-focus image is to
      use wavelet-based image fusion. First, several source images with different
      focuses of the same scene are taken and processed with the discrete wavelet
      transform (DWT). Among these wavelet decompositions, the wavelet coefficient with
      the largest magnitude is selected at each pixel location. Finally, the fused
      image can be recovered by performing the inverse DWT. In this paper, we improve
      this fusion procedure by applying the discrete wavelet frame transform (DWFT) and
      the support vector machines (SVM). Unlike DWT, DWFT yields a translation
      invariant signal representation. Using features extracted from the DWFT
      coefficients, a SVM is trained to select the source image that has the best focus
      at each pixel location, and the corresponding DWFT coefficients are then
      incorporated into the composite wavelet representation. Experimental results show
      that the proposed method outperforms the traditional approach both visually and
      quantitatively.

PMID- 15565782
TI  - New dynamical optimal learning for linear multilayer FNN.

PMID- 15565783
TI  - A columnar competitive model for solving combinatorial optimization problems.

PMID- 15565784
TI  - Perinatal asphyxia in the rat has lifelong effects on morphology, cognitive
      functions, and behavior.
AB  - Perinatal asphyxia (PA) is a major determinant of neurological morbidity and
      mortality in the neonatal period. Many studies have been investigating
      neurological deficits following PA, including seizures, cerebral palsy, mental
      retardation, as well as psychiatric deficits. Most research performed so far has
      been focusing on acute or subacute sequelae and has uncovered a variety of
      morphological, neurochemical, behavioral, and cognitive changes following PA.
      However, information on long-term sequelae of animals that underwent a period of
      PA is scanty. Perinatally asphyxiated rats at the end of their life span present
      with immunohistochemical and synaptic changes as well as changes in brain protein
      expression. Furthermore, deficits in cognitive function tested in the Morris
      water maze and changes in social behavior were described. In this review, we are
      summarizing and discussing reported effects of global PA on morphology, cognitive
      functions, and behavior in rats at the end of their life span.

PMID- 15565785
TI  - Apoptosis and neurogenesis after transient hypoxia in the developing rat brain.
AB  - Perinatal brain damage following a hypoxic-ischemic episode has been considered
      for a long time as an irreversible phenomenon. However, recent studies have shown
      that various insults may induce de novo neurogenesis in the adult rodent brain.
      The present study tested the hypothesis that acute hypoxia may trigger
      neurogenesis in the developing brain. In vitro, the influence of transient
      hypoxia was analyzed on the outcome of embryonic rat neurons in culture. In vivo,
      the temporal profile of brain damage was monitored at the level of the CA1 layer
      of the hippocampus after the exposure to hypoxia of 1-day-old rats. The extent of
      cell loss and regeneration was evaluated after staining with DAPI. The
      characterization of newly generated cells was performed in the subventricular
      zone at 20 days postexposure by immunohistochemistry. Following hypoxia for 6
      hours, neuronal viability in the culture dishes was reduced by 36% at 96 hours,
      with a significant number of cell nuclei showing apoptosis features. In contrast,
      a 3-hour hypoxia apparently did not damage cultured neurons whose number
      increased by 14%. The Bax/Bcl-2 ratio tended to increase after 6-hour hypoxia and
      to decrease after 3-hour hypoxia. In vivo, hypoxia induced cell damage in the CA1
      subfield of the hippocampus, where the total number of cells was reduced by 27%
      at days 6-7 postreoxygenation, with histopathological hallmarks of apoptosis.
      This cell deficit was followed by a gradual recovery observable from day 20,
      suggesting a repair mechanism. Brain incorporation of BrdU in the subventricular
      zone revealed an accumulation of proliferating cells expressing the neuronal
      marker NeuroD. The present data demonstrate that a posthypoxic neurogenesis does
      occur during development and may account for brain protection.

PMID- 15565786
TI  - Increased peripheral chemoreceptor activity may be critical in destabilizing
      breathing in neonates.
AB  - Periodic breathing and apnea are common in neonates, yet the physiological
      mechanisms involved are not clear. A low arterial PO2 might magnify peripheral
      chemoreceptor contribution to breathing, with its baseline variability inducing
      major changes in ventilation, leading to instability of the respiratory control
      system. We hypothesized that neonates: (1) would depend much more on the
      peripheral chemoreceptor contribution to breathing than adult subjects and (2)
      their baseline arterial PO2 would sit on the steep portion of the
      ventilation/arterial PO2 relationship on the adult nomogram, making breathing
      prone to oscillate. We analyzed data from previous polygraphic recordings in four
      groups of subjects: small preterm infants [SPI; postconceptional age (PCA) 33+/-2
      weeks; n = 40], large preterm infants (LPI; PCA 36+/-2 weeks; n = 34), term
      infants (TI; PCA 42+/-1 week; n = 24), and adult subjects (AS; weight 63+/-2 kg;
      age 29+/-3 years, n = 16). Peripheral chemoreceptor activity was measured by: (1)
      the immediate decrease in ventilation and (2) apnea time during brief inhalation
      of 100% O2 (about 1 minute). We found that: (1) the immediate decrease in
      ventilation with 100% O2 was more pronounced in infants than in adult subjects
      (38+/-2 versus 6+/-5%), and in infants breathing periodically versus those
      breathing continuously; (2) the apnea time during 100% O2 was also significantly
      longer in periodic breathing infants; and (3) the TcPO2 was much lower in infants
      than in adult subjects (65+/-1 versus 93+/-1 Torr), and also lower in periodic
      versus continuously breathing infants. It was located significantly to the left
      of values for the adult subject, on the ventilation/arterial PO2 diagram. The
      data suggest that: (1) a substantial portion of baseline breathing activity early
      in life is maintained by increased peripheral chemoreceptor activity; and (2)
      neonates breathe irregularly with apneas due to the position of their arterial
      PO2 values on the ventilation/arterial PO2 diagram, in which a change in PO2
      produces a more significant change in ventilation than that observed later in
      life.

PMID- 15565787
TI  - Role of inhibitory neurotransmitter interactions in the pathogenesis of neonatal
      apnea: implications for management.

PMID- 15565788
TI  - Larger corpus callosum size with better motor performance in prematurely born
      children.
AB  - The objective of this study is to determine the relation between the size of the
      corpus callosum (CC) and motor performance in a population-based cohort of
      preterm children. Preterm born children (n = 221) with a gestational age less
      than or equal to 32 weeks and/or a birth weight below 1500 g were eligible for
      this study. At the age of 7 or 8 years, frontal, middle, posterior, and total
      areas (mm2) of the corpus callosum were measured on true midsagittal MRI. Due to
      anxiety of 10 children and motion artifacts in 7 other children, 204 MRIs could
      be assessed in the preterm group (mean GA 29.4 weeks, sd 2.0,mean BW 1200 g, sd
      323). The preterm group consisted of 15 children with cerebral palsy (CP) and 189
      children without CP. Motor function was established by using the Movement
      Assessment Battery for Children, and the Developmental Test of Visual Motor
      Integration was obtained. The same examinations were performed in 21 term born
      children. The mean total cross-sectional CC area was significantly smaller in
      preterm born infants compared with their term born controls (338 mm2 versus 422
      mm2, P < 0.0001). The preterm children with CP had significantly smaller mean CC
      areas compared with the preterms who did not develop CP (P < 0.0001-P < 0.002).
      However, the preterms born without CP also had significantly smaller body,
      posterior, and total CC areas compared with term born controls (P < 0.0001-P <
      0.002). Only the difference in frontal area measurements dilrc) -3.3 mm2/score
      point (95% CI -4.5, -2.1). The association existed in all parts of the CC but
      increased in the direction of the posterior part: frontal: lrc -0.8 mm2/score
      point (-1.2, -0.4), middle: lrc -1.1 mm2/score point (-1.7, -0.5) and posterior:
      lrc -1.4 mm2/score point (-1.8, -0.9). An association between CC area and its
      subareas and the standard scores of the VMI was also found. A larger CC was
      strongly related t o better scores onthe VMI test total area CC: lrc 0.05
      score/mm2 (95% CI 0.03, 0.07), frontal: lrc 0.12 score/mm2 (0.05,0.19), middle:
      lrc 0.10 score/mm2 (0.05, 0.15) and posterior: lrc 0.12 score/mm2 (0.06, 0.18).
      After adjustment for gestational age, birth weight, and total cerebral area,
      these associations were still significant. There is a strong association between
      the size of the corpus callosum (total midsagittal cross area as well as frontal,
      middle, and posterior area) and motor function in preterm children, investigated
      at school age. A poorer score on the Movement ABC was related to a smaller CC. A
      larger CC was strongly associated with better VMI standard scores.

PMID- 15565789
TI  - Outcome at 5 years of age of SGA and AGA infants born less than 28 weeks of
      gestation.
AB  - The objective of this study was to compare the outcomes at 5 years of age of SGA
      and AGA children born < 28 weeks of gestation. The method used was a longitudinal
      follow-up of a cohort of 37 dyads of SGA and AGA infants matched by gestational
      age (GA), gender, and date of delivery. Mean GA was 26+/-1.2 weeks, and BW was
      638+/-77 g for SGA and 833+/-134 g for AGA (P < 0.0001). The SGA infants remained
      lighter at 3, 24, and 60 months. Their head circumference was statistically
      smaller at 3 and 60 months, and their length remained lower but no longer
      statistically significant. There was no difference after the second year of life
      between SGA and AGA children in the need for rehospitalization (16% versus 11%)
      and the incidence of medical problems such as Otitis (38% versus 41%) and asthma
      (24% versus 30%). SGA exhibited more neurodevelopmental deficits (41% versus 30%)
      and severe handicaps, including CP, blindness, deafness, and mental retardation
      (22% versus 14%). Those deficits were seen predominantly in association with
      microcephaly, which was more prevalent in the SGA group. We conclude that the
      combination of severe prematurity and intrauterine growth retardation constitutes
      a serious developmental handicap and predisposes to physical and developmental
      delays. The presence of microcephaly further aggravates the prognosis.

PMID- 15565790
TI  - School performance in adolescents with and without periventricular
      intraventricular hemorrhage in the neonatal period.
AB  - Long-term sequelae of preterm birth have been studied extensively up until the
      age of 5 to 8 years. However, the cognitive development of adolescents born
      preterm has received limited attention. The objective of this study is to
      determine school performance in adolescents born very preterm. We have followed
      up a cohort of 484 infants born before 32 weeks of gestation in whom cranial
      ultrasound was routinely and systematically performed. School performance was
      assessed in the surviving adolescents at 14 years of age. The outcome variable
      divided the adolescents into three groups: (1) normal, (2) slow learners, and (3)
      special education. School performance data were obtained from 278 of 304
      surviving adolescents; 129 performed normally, while 107 were slow learners, and
      42 needed special education. From the unadjusted odds ratios for the need of
      special education by the various perinatal factors, only the odds ratio for
      periventricular-intraventricular hemorrhage was significantly associated (2.56,
      95% confidence interval 1.17-4.86). Logistic regression analysis revealed that,
      after correction for possible confounding factors, the odds ratios for special
      education were significantly higher for adolescents with all grades of
      periventricular-intraventricular hemorrhage. Less than 50% of adolescents born
      before 32 weeks gestation perform normally in school. Periventricular
      intraventricular hemorrhage, including the lower grades,does have an unfavorable
      additional effect on school performance.

PMID- 15565791
TI  - First line of defense in early human life.
AB  - Innate antimicrobial peptides are considered to play an important role in host
      defense against microbial invasion. They are expressed in a wide variety of
      organisms. In the case of human beings, defensins and the cathelicidin LL-37
      appear to be the major microbicidal peptides. With respect to human neonates,
      only few investigations have been performed in this context, revealing the
      presence of alpha-defensins and LL-37 in neutrophils and vernix caseosa. In
      addition, beta-defensins are present in tracheal aspirates and breast milk,
      whereas LL-37 has been detected in the skin of the newborn baby. During recent
      years, immunomodulatory activities such as chemotaxis have emerged as important
      functions of antimicrobial peptides. Thus, these innate effectors may work
      synergistically to provide a first line of defense against infection, as well as
      to promote interactions between the innate and adaptive immunity in newborn
      infants.

PMID- 15565792
TI  - Developmental changes in NO bioavailability in fetal erythrocytes.
AB  - S-nitrosohemoglobin (HbSNO), where hemoglobin (Hb) is nitrosated at Cysbeta93,
      presumably controls delivery of the vasorelaxant nitric oxide (NO) to hypoxic
      tissues in an oxygen-sensitive manner. Little is known about how Hb regulates NO
      bioavailability during fetal development. A study was planned to determine the
      levels of HbSNO and HbFe(II)NO (NO bound to FeII of heme) in the cord blood of
      newborn infants of different gestational ages and establish their relationship
      with the levels of fetal Hb (HbF). Blood samples were collected from umbilical
      cord obtained from normal newborns between 24 and 41 weeks of gestation.
      Determinations of HbSNO and HbFe(II)NO were performed using chemiluminescence.
      The proportion of HbF was determined by HPLC. There were 11 preterm (24-34 weeks
      of gestation) and 11 term infants (37-41 weeks of gestation). The levels of HbSNO
      varied from 0.37 to 1.72 x 10(-5) mol/mol heme. There was a significant
      correlation with gestational age (r2 = 0.46, P = 0.0005) due to the effect of the
      decrease in the amount of HbF (r2 = 0.81, P < 0.0001). The relationship of
      HbFe(II)NO was not affected by gestational age or the level of HbF (mean 1.68+/
      1.15 x 10(-5) mol/mol heme). Under physiological in utero conditions, fetal
      erythrocytes have lower levels of HbSNO, which increase in the later stage of
      fetal development. The levels of HbSNO in the fetal red cell are dependent on the
      level of adult Hb (HbA). The low HbSNO levels at physiological fetal O2
      saturations during early development could protect the fetal circulation from an
      excess release of NO and O2.

PMID- 15565793
TI  - Undergraduate student enrollment: a dream come true or a nightmare on Elm street?

PMID- 15565794
TI  - The Disney story.

PMID- 15565795
TI  - Molecular imaging II. Molecular imaging is still receiving attention.

PMID- 15565796
TI  - Targeted imaging using ultrasound contrast agents. Progess and opportunities for
      clinical and research applications.

PMID- 15565797
TI  - Magnetic resonance spectroscopic imaging. Evaluating responses to therapy for
      gliomas.

PMID- 15565798
TI  - A hyperspectral imaging system for in vivo optical diagnostics. Hyperspectral
      imaging basic principles, instrumental systems, and applications of biomedical
      interest.

PMID- 15565799
TI  - Molecular imaging and therapy directed at the neovasculature in pathologies. How
      imaging can be incorporated into vascular-targeted delivery systems to generate
      active therapeutic agents.
AB  - We have discussed the impact of molecular imaging on clinical and preclinical
      medicine. We have presented the potential problems of delivering the effective
      therapeutic dose and the properties that can help contribute to the drug
      efficacy. The rationale for the design of new antiangiogenic agents that can be
      used for imaging and therapy was presented. Finally, results from imaging and
      targeted nanoparticle based therapies were presented. In vivo imaging of
      angiogenic tumors using anti-alpha(v)beta3 -targeted polymerized vesicles
      composed of the murine antibody LM609 attached to NPs labeled with the MR
      contrast agent gadolinium in the V2 carcinoma model in rabbits. MRI studies using
      this targeted contrast agent revealed large areas of alpha(v)beta3 integrin
      expression in tumor-associated vasculature that conventional MRIs failed to show.
      Other investigators have used microemulsions conjugated to an antibody targeted
      against alpha(v)beta as imaging agents. These materials also show contrast
      enhancement of tumor vasculature undergoing angiogenesis. Other markers, such as
      the PECAM-1 (CD-31), VCAM-1 (CD54) and VEGF receptor (flk-1), have been shown to
      be upregulated on tumor endothelium and associated with angiogenesis but have not
      been used in imaging studies. Furthermore, by modification of the NPs, we were
      able to use this imaging agent as an antiangiogenic gene delivery system. The
      results from these studies are very promising and are being further pursued.

PMID- 15565800
TI  - pH imaging. A review of pH measurement methods and applications in cancers.
AB  - Acid-base balance is altered in a variety of common pathologies, including COPD,
      ischemia, renal failure, and cancer. Because of robust cellular pH homeostatic
      mechanisms, most of the pathological alterations in pH are expressed as changes
      in the extracellular, systemic pH. There are data to indicate that altered pH is
      not simply an epiphenomenon of metabolic or physiologic imbalance but that
      chronic pH alterations can have important sequelae. MRSI and MRI measurements
      indicate that pH gradients of up to 1.0 pH unit can exit within 1-cm distance.
      Although measurement of blood pH can indicate systemic problems, it cannot
      pinpoint the lesion or quantitatively assess the magnitude of excursion from
      normal pHe. Hence, there is a need to develop pHe measurement methods with high
      spatiotemporal resolution. The two major approaches being investigated include
      magnetization transfer methods and relaxation methods. pH-dependent MT effects
      can observed with endogenous signals or exogenously applied CEST agents. While
      endogenous signals have the advantage of being fully noninvasive and relatively
      straightforward to apply, they lack a full biophysical characterization and
      dynamic range that might be afforded by future CEST agents. pH-dependent
      relaxivity also requires the injection or infusion of exogenous contrast
      reagents. In both MT and relaxographic approaches, the magnitude of the effect,
      and, thus, the ability to quantify pHe, depends on a spatially and temporally
      varying concentration of the CR. A number of approaches have been proposed to
      solve this problem and, once it is solved, pH imaging methods will be applicable
      to human clinical pathologies.

PMID- 15565801
TI  - Dynamic magnetic resonance imaging of tumor perfusion. Approaches and biomedical
      challenges.

PMID- 15565802
TI  - News in brief: challenges and directions in biomaterials research.

PMID- 15565803
TI  - Technology hits the road.

PMID- 15565804
TI  - Prognostic role of Ebstein-Barr virus latent membrane protein-1 and interleukin
      10 expression in patients with nasopharyngeal carcinoma.
AB  - PURPOSE: We aimed to investigate Ebstein-Barr virus (EBV) latent membrane protein
      1 (LMP-1) and Interleukine-10 (IL-10) expression in nasopharyngeal carcinoma
      (NPC) patients and to evaluate their prognostic significance. MATERIAL AND
      METHODS: Between 1993 and 1999, 166 patients were treated with the diagnosis of
      nonmetastatic NPC at our department. The expression of LMP-1 and IL-10 was
      investigated by using an immunohistochemical approach in 74 (53 male, 21 female)
      patients whose paraffin embedded tissue samples were available. A detailed
      histopathological analysis including degree of apoptosis and lymphocyte
      infiltration was made and all patients were reclassified according to the World
      Health Organization (WHO) classification. Univariate, multivariate, and logistic
      regression analyses were performed using all clinical and pathological prognostic
      factors. All patients were treated with radiotherapy +/- chemotherapy. Follow-up
      ranged between 12 and 80 months (median: 32). RESULTS: The histopathological
      diagnosis was WHO-I in 1 (1.3%), WHO-II in 15 (20.2%), and WHO-III in 58 (79.5%)
      patients. There were 38 (51%) patients with IL-10 expression and 44 (61%)
      patients with LMP-1 expression. Twenty-seven (36.4%) patients were found to be
      both IL-10 and LMP-1 positive. There were significantly more N0 disease in
      patients without LMP-1 expression compared to LMP-1 positive patients (65% vs.
      35%, p = 0.01). The logistic regression analysis showed advanced nodal
      involvement to be the major parameter affecting the expression of IL-10 (p =
      0.03). Three-year overall survival (OS), locoregional relapse free survival
      (LRRFS), and distant metastasis free survival (DMFS) rates were 67.8%, 84.4%, and
      74.3%, respectively, for the whole group. On univariate analysis, LRRFS was
      significantly lower in WHO-III patients, DMFS was significantly lower in advanced
      nodal disease and IL-10 negative patients, and OS was significantly lower in WHO
      III patients. Multivariate analysis showed that WHO-III and T2 patients were
      significantly associated with lower OS and N3 patients were significantly
      associated with lower DMFS. CONCLUSION: We observed a high rate (61%) of EBV (LMP
      1 positive) and NPC association in our patients. LMP-1 positive tumors were found
      to be more prone to invade lymph nodes. Patients with negative IL-10 expression
      had more advanced N disease. We did not find a prognostic significant role of IL
      10 and EBV LMP-1 on survival in multivariate analysis.

PMID- 15565805
TI  - A comparison of survival rates for treatment of melanoma metastatic to the brain.
AB  - INTRODUCTION: A retrospective review of 91 patients with brain metastases from
      malignant melanoma treated at New York University Medical Center between 1989
      1999. Overall survival was the outcome evaluated. METHODS: Charts of 91 patients
      having malignant melanoma with brain metastases were reviewed. Cases were
      stratified according to therapy: surgical excision, surgical excision plus whole
      brain radiation therapy, gamma knife stereotactic radiosurgery, gamma knife
      stereotactic radiosurgery plus whole brain radiation therapy, and whole brain
      radiation therapy alone. Patients treated with gamma knife stereotactic
      radiosurgery plus radiation therapy were combined with patients treated with
      surgical excision plus radiation therapy and compared to those treated with
      radiation therapy alone. Prognostic characteristics of the two groups were
      compared and survival curves were generated using the Kaplan-Meier method. The
      Cox proportional hazards model was used to control for prognostic factors that
      differed between the groups. RESULTS: Patients treated with gamma knife
      stereotactic radiosurgery or surgical excision plus radiation therapy were
      younger, less likely to present with symptoms, and presented with fewer
      metastases to the brain than patients treated with radiation therapy alone. A
      survival benefit of 7.3 months (p = 0.05) was found to be associated with gamma
      knife radiosurgery or surgical excision plus radiation therapy over radiation
      therapy alone after controlling for differences in age, number of brain lesions,
      and presence of symptoms. DISCUSSION: This retrospective study of 91 patients
      treated for melanoma metastases to the brain attempts to examine the
      effectiveness of different treatments in prolonging survival. Our results suggest
      that surgical excision or stereotactic radiosurgery with gamma knife in addition
      to radiation therapy may be more effective than radiation alone at prolonging
      survival for patients with a limited number of brain lesions. CONCLUSION:
      Survival of patients with melanoma metastases to the brain may be prolonged by
      treatment with gamma knife stereotactic radiosurgery or surgical excision plus
      whole brain radiation therapy.

PMID- 15565806
TI  - Does 99mTc-sestamibi uptake discriminate breast tumors?
AB  - The aim of this work was to investigate 99mTc-sestamibi uptake and
      histopathological characteristics of breast tumors. Static 99mTc-sestamibi
      scintimammography (SMM) has been performed in 101 breast tumors (98 patients).
      SMM were scored from 0 to 4 according to intensity of 99mTc-sestamibi uptake and
      classified in two groups: SMM with absence or low tumor uptake (0, 1, 2) and SMM
      with high tumor uptake (3, 4). Tumor histopathological characteristics have been
      determined on core or excisional biopsy. The 99mTc-sestamibi uptake (low vs.
      high) correlated to classical prognostic factors: positively with Scarff-Bloom
      and Richardson (SBR) grade (p < 0.0005), axillary involvement (p < 0.0005), and
      tumor size (p < 0.0005) and negatively with estrogen receptors (p < 0.001).
      Fixation of 99mTc-sestamibi in invasive lobular carcinoma was lower than in
      invasive ductal carcinoma (p < 0.01) despite a similar mean tumor size (28 +/- 14
      mm vs. 24 +/- 14 mm). Relations between 99mTc-sestamibi uptake and tumor size,
      histologic type, and axillary involvement were independent variables also
      significant in multivariate analysis (p < 0.0005, p < 0.005, p < 0.05,
      respectively). Moreover, the five-year survival rate was higher when 99mTc
      sestamibi breast tumor uptake was low (p < 0.005). This difference is also
      significant using the Cox model (p < 0.05). Uptake of 99mTc-sestamibi (low vs.
      high) discriminates breast tumors with different histopathological
      characteristics and prognosis.

PMID- 15565807
TI  - Gemcitabine combined with docetaxel for the treatment of unresectable pancreatic
      carcinoma.
AB  - PURPOSE: To assess the efficacy and toxicity of combination therapy with
      gemcitabine and docetaxel in patients with unresectable pancreatic carcinoma.
      PATIENTS AND METHODS: Thirty-four patients with unresectable stage III, IVA, and
      IVB pancreatic carcinoma were eligible for this study. The first 18 patients
      received gemcitabine 800 mg/m2 intravenously (i.v.) on days 1, 8, and 15 and
      docetaxel 75 mg/m2 i.v. on day 1, repeated every 28 days. Due to a high incidence
      of myelosuppression in this first group, the treatment schedule was modified in
      the remaining patients to gemcitabine 1,000 mg/m2 i.v. and docetaxel 40 mg/m2
      i.v. on days 1 and 8 of a 21-day schedule. The primary study endpoints were
      objective response rate and duration of survival. RESULTS: Ten of 33 evaluable
      patients achieved a partial response, for an overall response rate of 30.3% (95%
      CI, 16.21%-48.87%). Partial responses noted in the pancreas and a variety of
      metastatic sites were maintained for 4 to 12 months (median 6 months). Twelve
      additional patients (36%) experienced stable disease. The median time to
      progression was 6 months, and median survival was 10.5 months. The toxicity
      profile of the modified gemcitabine/docetaxel schedule was more favorable than
      that associated with the initial regimen, particularly with respect to
      hematologic toxicity. CONCLUSION: The response and survival data reported here
      for combination therapy with gemcitabine and docetaxel are encouraging given the
      poor prognosis associated with unresectable pancreatic cancer. These data suggest
      that gemcitabine plus docetaxel may be more effective than either agent alone in
      the treatment of pancreatic cancer and warrants further study.

PMID- 15565808
TI  - Pilot evaluation of black cohosh for the treatment of hot flashes in women.
AB  - BACKGROUND: Hot flashes cause significant morbidity in postmenopausal women,
      including women with breast cancer. We undertook a pilot study to estimate the
      effectiveness of black cohosh to reduce hot flashes. METHODS: Women who reported
      significant hot flashes (> or = 14 per week) were enrolled. Black cohosh was
      given in the form of the commercial product Remifemin. The first week was a no
      treatment baseline period, and therapy was given for the subsequent 4 weeks. Hot
      flash data were collected by daily questionnaires during baseline and treatment
      weeks. Adverse effects were recorded. RESULTS: Twenty-one women completed the
      study. Their mean age was 56 years (range, 38-80). Thirteen patients had a
      history of breast cancer. Six patients were taking tamoxifen or raloxifene.
      Patients reported an average of 8.3 hot flashes per day during the baseline week.
      The reduction in mean daily hot flash frequency was 50% (95% CI, 34%-65%), while
      weekly hot flash scores were reduced 56% (95% CI, 40%-71%) at completion of the
      study. Overall, patients reported less trouble with sleeping, less fatigue, and
      less abnormal sweating. No patients stopped therapy because of adverse effects.
      CONCLUSIONS: Black cohosh appeared to reduce hot flashes and had a low toxicity.
      The efficacy found in this trial seems to be more than would be expected by a
      placebo effect (20%-30% hot flash reduction in previous trials). These results
      suggest that further evaluation of this black cohosh preparation with a phase III
      randomized trial is indicated.

PMID- 15565809
TI  - TRAIL induction by radiation in lymphoma patients.
AB  - TRAIL/Apo-2 L, a member of the Tumor Necrosis Factor cytokine family, induces
      apoptosis specifically in malignant cells. A combination of TRAIL and radiation
      is highly synergistic in in vitro experiments. In addition to this additive
      effect, we observed that TRAIL is induced by irradiation of certain cell lines.
      The induction begins approximately 2 hours after irradiation. This might even
      enhance the antineoplastic effect of ionizing radiation and partially explain the
      abscopal effect observed in hematopoietic malignancies. TRAIL levels were
      evaluated in 17 patients treated with radiation for Hodgkin's and non-Hodgkin's
      lymphoma. We did not observe a specific TRAIL expression pattern that could be
      correlated with histology, disease status, volume of disease, radiation dose, and
      other antineoplastic therapies, but a definite pattern observed in a single
      patient remained constant over time. TRAIL and interferons display a common
      pattern of gene expression at certain nodal points of interaction between the two
      physiologic pathways. Our hypothesis is that the radiation-induced changes in
      TRAIL expression observed in patients undergoing therapeutic radiation may be
      emblematic of the various physiologic pathways induced or inhibited by ionizing
      radiation and may even be partially responsible for the "bystander effect"
      observed in unirradiated cells in close proximity to irradiated cells.

PMID- 15565810
TI  - Shorter symptom assessment instruments: the Condensed Memorial Symptom Assessment
      Scale (CMSAS).
AB  - BACKGROUND: Rapid and efficient symptom assessment is an important aspect of
      palliative care. The objective was to determine whether a smaller number of
      symptoms from the 32-item Memorial Symptom Assessment Scale Short-Form (MSAS-SF)
      could convey equivalent quality of life (QOL) information. METHODS: Responses
      from 479 medical oncology patients who completed the MSAS-SF and the Functional
      Assessment Cancer Therapy (FACT-G) were analyzed. Canonical correlations were
      performed to assess the relationships of 32 MSAS-SF symptoms to quality of life
      (FACT-G domains) and clinical variables [age, Karnofsky performance status (KPS),
      stage of disease, and inpatient status]. The relation of the subscales of the
      Condensed MSAS (CMSAS) and FACT-G to survival was assessed in a multivariate
      model. RESULTS: The median age was 67 years (range, 20-89) and median KPS was 80%
      (range, 20-100). Primary sites were prostate in 141 (29%) patients, lung in 121
      (26%) patients, colorectal in 53 (11%) patients, hematologic in 50 (10%)
      patients, head and neck in 30 (6%) patients and other in 84 (18%) patients.
      Median survival was 245 days (range, 1-2,215 days). Canonical correlation
      analyses identified a five-dimensional QOL factor structure. Symptoms important
      for QOL also correlated significantly with survival and provided the basis for
      the CMSAS with 14 symptoms and 3 subscales (CMSAS SUM, CMSAS PHYS, and CMSAS
      PSYCH). In multivariate analyses, the CMSAS PSYCH predicted survival
      independently of stage, performance status, and QOL. The CMSAS takes 2-4 minutes
      to complete. CONCLUSION: The CMSAS contains both QOL and survival information
      approximately equivalent to the original 32 items.

PMID- 15565811
TI  - Determination of HER-2/neu overexpression and clinical predictors of survival in
      a cohort of 347 patients with primary malignant brain tumors.
AB  - INTRODUCTION: HER-2/neu overexpression has been associated with poor prognosis in
      a variety of malignancies. The extent and relevance of HER-2/neu overexpression
      in human central nervous system (CNS) malignancies is unclear. We retrospectively
      analyzed a large cohort of patients with primary malignant brain tumors to
      evaluate the role of HER-2/neu overexpression, clinical characteristics at
      presentation, and other predisposing factors as predictors of survival. MATERIALS
      AND METHODS: Records of 347 adult patients (193 males, 154 females) diagnosed and
      followed between 1986 and 2001 with a biopsy-proven diagnosis of a primary
      malignant brain tumor at a tertiary care oncology center were reviewed. Archival
      pathologic samples were analyzed for HER-2/neu overexpression using the Hercep
      immunohistochemical (IHC) assay (DAKO). A score of 2+ or greater on the assay was
      considered positive for HER-2/neu overexpression. Mortality and its predictors
      were evaluated using multiple logistic regression. (This study was approved and
      reviewed by the Institutional Review Board Committee [IRB] of University of North
      Dakota School of Medicine and Health Sciences.) RESULTS: Among the 347 adult
      patients with a mean age of 53 years (range; 41-73 years), overall mean survival
      was 23 months (range; 0-151 months). It was found that 10.4% of the archival
      pathologic samples showed presence of HER-2/neu overexpression by IHC. The HER
      2/neu overexpression predicted significantly increased mortality [p = 0.01,
      analysis of variance (ANOVA)]. Other clinical predictors associated with
      increased mortality included site of tumor (occipital and parietal lobes) (p =
      0.02, ANOVA), tumor histology (glioblastoma) (p < 0.01, ANOVA), and presenting
      symptom (nausea/vomiting) (p < 0.01, ANOVA). Also, there was a higher incidence
      of associated primary malignancies (outside the CNS) in the HER-2/neu
      overexpression group (30% vs. 7%). CONCLUSIONS: HER-2/neu overexpression seen in
      10.4% appears to predict a slight increased mortality in patients with primary
      malignant brain tumors, especially glioblastoma multiforme, and is associated
      with a high incidence of a second primary malignancy outside the CNS.
      Additionally, our data suggests that other clinical variables were predictive of
      increased mortality, including tumor location (occipital), histology
      (glioblastoma), and presenting symptoms (nausea/vomiting). The large,
      heterogeneous sample employed in our study allows more definitive conclusions to
      be made with regard to the usefulness of HER-2/neu and other clinical predictors
      of survival in patients with primary brain tumors.

PMID- 15565812
TI  - Complete remission of previously intractable peripheral cutaneous T-cell lymphoma
      of the lower extremity using isolated hyperthermic limb perfusion with melphalan
      (1-phenylalanine mustard).
AB  - The patient is a 74-year-old woman first diagnosed with a peripheral cutaneous T
      cell lymphoma (PCTCL) in April of 1994. Initially she presented with subcutaneous
      indurated areas in the right forearm, scapula, and submadibular region. After
      chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and
      prednisone), she went into remission for 2 years before relapse of her PCTCL
      localized to the right lower extremity. Persistent isolated disease in the
      extremity since then led to numerous chemotherapy regimens and localized
      radiation therapy. Due to dramatic limb threatening progression of the disease in
      2001, she underwent isolated hyperthermic limb perfusion with melphalan (1
      phenylalanine mustard). Although limb preservation could not be achieved, this
      treatment resulted in complete clinical and pathological regression of the
      lesions of the perfused extremity.

PMID- 15565813
TI  - Hepatic arterial infusion of paclitaxel for liver metastasis from gastric cancer.
AB  - Little is known about hepatic arterial infusion (HAI) of paclitaxel for hepatic
      malignancies. The authors administered paclitaxel via the HAI port in two
      patients with liver metastases from gastric cancer. Both patients were
      uneventfully treated without any serious complications, and its anti-tumor effect
      on 5-fluouracil resistant liver metastases was confirmed. However, the kinetics
      of venous paclitaxel concentration following HAI was similar to that after
      intravenous injection. Our findings did not support the advantage of paclitaxel
      HAI therapy, although HAI of this agent was well tolerated.

PMID- 15565814
TI  - Dose density in adjuvant chemotherapy for breast cancer.
AB  - BACKGROUND: Dose-dense chemotherapy increases the dose intensity of the regimen
      by delivering standard-dose chemotherapy with shorter intervals between the
      cycles. This article discusses the rationale for dose-dense therapy and reviews
      the results with dose-dense adjuvant regimens in recent clinical trials in breast
      cancer. METHODS: The papers for this review covered evidence of a dose-response
      relation in cancer chemotherapy; the rationale for dose-intense (and specifically
      dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant
      chemotherapy for breast cancer, with particular attention to outcomes and
      toxicity. RESULTS: Evidence supports maintaining the dose intensity of adjuvant
      chemotherapy within the conventional dose range. Disease-free and overall
      survival with combination cyclophosphamide, methotrexate, and fluorouracil are
      significantly improved when patients receive within 85% of the planned dose.
      Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the
      standard range results in greater disease-free and overall survival than the low
      dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin
      and cyclophosphamide also significantly improves survival. Disease-free and
      overall survival with dose-dense sequential or concurrent doxorubicin,
      cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are
      significantly greater than with conventional schedules (q21d). CONCLUSIONS: The
      delivered dose intensity of adjuvant chemotherapy within the standard dose range
      is an important predictor of the clinical outcome. Prospective trials of high
      dose chemotherapy have shown no improvement over standard regimens, and toxicity
      was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with
      doxorubicin-containing regimens. Filgrastim support enables the delivery of dose
      dense chemotherapy and reduces the risk of neutropenia and its complications.

PMID- 15565815
TI  - Role of neurokinin-1 receptor antagonists in chemotherapy-induced emesis: summary
      of clinical trials.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant
      deterioration in quality of life, and although the use of 5-hydroxytryptamine3 (5
      HT3) receptor antagonists plus dexamethasone has significantly improved the
      control of acute CINV, delayed nausea and vomiting remain a significant clinical
      problem. Aprepitant is the first agent available in the new drug class of
      neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3
      receptor antagonist and dexamethasone in patients receiving highly emetogenic
      chemotherapy, it improves the complete response rate of acute CINV. Aprepitant
      also improves the complete response of delayed CINV when used in combination with
      dexamethasone compared to dexamethasone alone. The use of aprepitant in patients
      receiving moderately emetogenic chemotherapy will await the review and analysis
      of recently completed phase III trials. The control of nausea is improved in some
      studies with the use of aprepitant when it is combined with a 5HT3 receptor
      antagonist and dexamethasone, but nausea control remains suboptimal. The current
      data suggest that the mechanism of action of the NK-1s appears to be different
      from the 5-HT3 receptor antagonists. Future studies may explore the use of
      aprepitant and other NK-1s in moderately and highly emetogenic chemotherapy, as
      well in the clinical settings of multiple-day chemotherapy and bone marrow
      transplantation.

PMID- 15565816
TI  - Progress report on the potential of angiogenesis inhibitors for neuro-oncology.
AB  - New therapies for brain tumors are urgently needed. Brain tumors are highly
      vascularized, supporting the potential of anti-angiogenic therapies in their
      treatment. The promise of blocking tumor growth through inhibiting new blood
      vessel formation with anti-angiogenic agents has been heralded as a therapeutic
      breakthrough, and pre-clinical data supported this enthusiasm. However, early
      clinical trials in humans have been somewhat disappointing. Nonetheless, great
      optimism for these agents remains, and many new anti-angiogenic agents and
      strategies are being evaluated pre-clinically and in clinical trials. A number of
      issues need to be considered in the application of these agents to neuro
      oncology. In this review, we discuss the biology of blood vessel formation in the
      brain and brain tumors as it relates to anti-angiogenic therapies. The
      difficulties inherent in performing clinical trials of anti-angiogenic therapies
      in patients with brain tumors are outlined. Finally, we consider numerous
      individual antiangiogenic and antivascular therapies now in pre-clinical testing
      or in clinical trials.

PMID- 15565817
TI  - The tuberous sclerosis complex genes in tumor development.
AB  - The study of hereditary tumor syndromes has laid a solid foundation toward
      understanding the genetic basis of cancer. One of the latest examples comes from
      the study of tuberous sclerosis complex (TSC). As a member of the phakomatoses,
      TSC is characterized by the appearance of benign tumors, most notably in the
      central nervous system, kidney, heart, lung, and skin. While classically
      described as "hamartomas," the pathology of the lesions has features suggestive
      of abnormal cellular proliferation, size, differentiation, and migration.
      Occasionally, tumors progress to become malignant (i.e., renal cell carcinoma).
      The genetic basis of this disease has been attributed to mutations in one of two
      unlinked genes, TSC1 and TSC2. Cells undergo bi-allelic inactivation of either
      gene to give rise to tumors in a classic tumor suppressor "two-hit" paradigm. The
      functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively,
      have remained ill defined until recently. Genetic, biochemical, and biologic
      analyses have highlighted their role as negative regulators of the mTOR signaling
      pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity
      by coordinating inputs from growth factors and energy availability in the control
      of cell growth, proliferation, and survival. Emerging evidence also suggests that
      the TSC 1/2 complex may play a role in modulating the activity of beta-catenin
      and TGFbeta. These findings provide novel functional links between the TSC genes
      and other tumor suppressors responsible for Cowden's disease (PTEN), Peutz
      Jeghers syndrome (LKB1), and familial polyposis (APC). Common sporadic cancers
      such as prostate, lung, colon, endometrium, and breast have ties to these genes,
      highlighting the potential role of the TSC proteins in human cancers. Rapamycin,
      a specific mTOR inhibitor, has potent antitumoral activities in preclinical
      models of TSC and is currently undergoing phase I/II clinical studies.

PMID- 15565818
TI  - Tumor-activated prodrugs--a new approach to cancer therapy.
AB  - Systemic cytotoxic (antiproliferative) anticancer drugs rely primarily for their
      therapeutic effect on cytokinetic differences between cancer and normal cells.
      One approach aimed at improving the selectivity of tumor cell killing by such
      compounds is the use of less toxic prodrug forms that can be selectively
      activated in tumor tissue (tumor-activated prodrugs; TAP). There are several
      mechanisms potentially exploitable for the selective activation of TAP. Some
      utilize unique aspects of tumor physiology such as selective enzyme expression or
      hypoxia. Others are based on tumor-specific delivery techniques, including
      activation of prodrugs by exogenous enzymes delivered to tumor cells via
      monoclonal antibodies (ADEPT) or generated in tumor cells from DNA constructs
      containing the corresponding gene (GDEPT). Whichever activating mechanism is
      used, only a small proportion of the tumor cells are likely to be competent to
      activate the prodrug. Therefore, TAP need to fully exploit these "activator"
      cells by being capable of killing activation-incompetent cells as well via a
      "bystander effect." A wide variety of chemistries have been explored for the
      selective activation of TAP. Examples are given of the most important-the
      reduction of quinones, N-oxides, and nitroaromatics by endogenous enzymes or
      radiation; the cleavage of amides by endogenous peptidases; and hydrolytic
      metabolism by a variety of exogenous enzymes, including phosphatases, kinases,
      amidases, and glycosidases.

PMID- 15565819
TI  - Fine needle aspiration.
AB  - Fine needle aspiration (FNA) has been widely used as a diagnostic tool for the
      past half century. Differing from large bore cutting needle biopsy, FNA utilizes
      22- to 27-gauge needles. The cell samples aspirated from a lesion are
      characteristically smeared on glass slides for immediate microscopic evaluation.
      An adequacy report and a preliminary diagnostic impression are rendered in
      approximately 10 to 15 minutes. A final report is generally rendered within 24
      hours. The method has been used as one of the most cost-effective, complication
      free, and rapid techniques for preoperative investigation of tumors and tumor
      like conditions. Its usefulness in the diagnosis and management of oncology
      patients is emphasized in this article.

PMID- 15565820
TI  - Interventional procedures for cancer pain management: when are they indicated?
AB  - Non-invasive pharmacological management of patients with cancer related pain has
      resulted in pain control in 90-95% of the patients. Thus, 5-10% of patients still
      experience inadequate pain control despite aggressive combined pharmacological
      therapy. Moreover, patients may not tolerate an aggressive program of titration
      of medications and fail this approach because of side effects. In these patients
      interventional techniques have been very useful. This article discusses the
      alternative therapies, as well as the pitfalls in implementing these therapies,
      to achieve the highest possible success while minimizing potential complications
      and side effects.

PMID- 15565821
TI  - RE: A comparison of survival rates for treatment of melanoma metastatic to the
      brain.

PMID- 15565822
TI  - Can an herbal agent replace estrogen for hot flashes?

PMID- 15565823
TI  - Dose intensity ... and beyond.

PMID- 15565824
TI  - Effect of filgrastim on serum lactate dehydrogenase and alkaline phosphatase
      values in early breast cancer patients.
AB  - To improve chemotherapy dose intensity and to optimize the use of granulocyte
      colony stimulating factor, 506 patients with early breast cancer were randomly
      assigned to high dose epirubicin and cyclophospamide (EC) with or without
      prophylactic subcutaneously filgrastim, according to 5 different schedules: 480
      microg or 300 microg daily or every other day, on day 8 through day 14, and 300
      microg daily on days 8 and 12 of each chemotherapy course, Serum levels of
      lactate dehydrogenase (LDH) and alkaline phosphatase (AP) were significantly
      higher in patients given EC plus filgrastim than EC alone (P = 0.0001), the rate
      of G1-3 toxicity being 33.4% and 13.1% vs. 1.6% and 1%, respectively. No clinical
      evidence of filgrastim-related hepatic damage or significant difference in
      transaminase and gamma-GT elevation was seen between the two groups. LDH and AP
      closely resembled peripheral blood leukocytes count and increased with increasing
      leucocytosis, throughout the 5 schedules. Although no patient continued treatment
      for filgrastim-related side effects, and LDH and AP rises resolved spontaneously
      within 3 weeks following the chemotherapy course, physicians should be aware of
      the transient and innocuous change in serum chemistry associated to leucocytosis,
      since it could be misinterpreted as expression of disease activity.

PMID- 15565825
TI  - Attributions toward violence of male juvenile delinquents: a concurrent mixed
      methodological analysis.
AB  - The authors investigated male juvenile delinquents' causal attributions about
      others' behavior and the salient pieces of information that the male juveniles
      used in arriving at their attributions. Participants were 82 male juvenile
      offenders whom the authors drew randomly from the population of juveniles who
      were incarcerated at a correctional facility. A concurrent mixed-methodological
      analysis revealed that the juvenile offenders committed attributional errors
      about violence nearly 53% of the time. Race and number of prior arrests predicted
      the number of attributional errors about violence. A phenomenological analysis
      revealed the following 7 themes stemming from juveniles' reasons for causal
      attributions: self-control, violation of rights, provocation, irresponsibility,
      poor judgment, fate, and conflict resolution. Some of these themes were related
      to age, ethnicity, and number of prior arrests. The authors discussed
      implications of all findings.

PMID- 15565826
TI  - From the front lines of welfare reform: an analysis of social worker and welfare
      recipient attitudes.
AB  - Social workers and welfare recipients operate within the same institutional
      framework and share a working and/or lived knowledge of poverty, but they occupy
      different social and economic positions. To gain a better understanding of
      intergroup attitudes, the author compared how social workers and welfare
      recipients explain poverty and perceive the welfare system. The results highlight
      important similarities and differences between the two groups. Although the
      author did not find differences for individualistic attributions, welfare
      recipients regarded prejudice as playing a greater role in causing poverty than
      did social workers. Welfare recipients also expressed stronger support for
      increased welfare funding and progressive welfare policies than did social
      workers. The author discussed implications for strengthening interclass
      alliances, particularly the relationship between social service providers and
      welfare recipients.

PMID- 15565827
TI  - The role of attributional retraining and elaborative learning in college
      students' academic development.
AB  - In the present longitudinal study, the authors examined the impact of
      attributional retraining (AR) techniques on academic motivation and achievement
      for college students who are either frequently or infrequently using elaborative
      learning strategies. During the 1st semester, 203 students completed an initial
      questionnaire assessing elaborative learning followed by 1 of 3 treatment
      conditions (No AR, Writing AR, Aptitude Test AR). Results indicated improvements
      in students' end-of-year perceptions of control, success, and emotions, as well
      as course-specific and overall academic performance for those receiving either AR
      format, with "high elaborators" showing higher levels on these measures than "low
      elaborators." The authors discussed the importance of elaborative and
      attributional processes underlying the effectiveness of the AR treatment and the
      potential utility of individualized AR techniques in the college classroom.

PMID- 15565828
TI  - Religiosity, values, and horizontal and vertical individualism-collectivism: a
      study of Turkey, the United States, and the Philippines.
AB  - The authors examined the links between two dimensions that have been useful in
      understanding cross-cultural differences and similarities, namely, individualism
      collectivism (I-C) and value orientations. The authors examined the relations and
      parallels between the two variables by directly relating them and examining the
      patterns of relations that both have with a third variable, religiosity.
      Participants were 475 college students from the Philippines, the United States,
      and Turkey who responded to measures of horizontal and vertical I-C, value
      orientations, and religiosity. The authors found partial support for the
      parallels between I-C and value types, particularly for collectivism and
      conservative values. Moreover, religiosity was associated positively with
      conservative values and collectivism, across all three cultures. The authors
      found individualism to also relate to openness-to-change values, though the
      patterns were not as consistent as those that they found between collectivism and
      conservation. Differences and similarities emerged in links of I-C-values to
      religiosity across the three samples.

PMID- 15565829
TI  - Clinical outcomes for newborn intensive care in Alaska.
AB  - Recent clinical outcomes for the Newborn Intensive Care Unit (NICU) at Providence
      Alaska Medical Center based on Alaska Neonatology's Clinical Outcomes Database
      are presented. There has been a decrease in overall mortality, with much of the
      improvement occurring in babies from 22 to 25 weeks gestation in the years 1998-
      2002. There has also been a decrease in the incidence of severe intraventricular
      hemorrhage / periventricular leukomalacia. Earlier discharge of babies has also
      been documented, as measured by post conceptual age at discharge. No improvement
      in the incidence of retinopathy of prematurity and nosocomial sepsis were seen.
      Rates of chronic lung disease and babies going home in oxygen have increased.
      Outcomes that have failed to improve are the focus of quality improvement
      initiatives. Clinical outcome information systems such as the NICU outcomes
      database are essential for assessing clinical performance and provide the
      foundation and focus for quality improvement initiatives.

PMID- 15565830
TI  - Non-fatal injury hospitalizations among Alaska natives, 1994--1999: results from
      the Alaska Trauma Registry.
AB  - The Alaska Trauma Registry collects data on injuries resulting in hospitalization
      or transfer to a higher level of care from every hospital in the state. We
      analyzed non-fatal injuries to Alaska Native and White residents from 1994--1999.
      Statewide, the five most common causes of injuries to Alaska Natives were falls,
      suicide attempts, off-road vehicles, motor vehicles, and assaults. These
      accounted for two-thirds of all injuries; falls accounted for 26.3% of all
      injuries. For total injuries and for each cause, injury rates were significantly
      higher for Alaska Natives than Alaska Whites. The greatest discrepancies were for
      suicide attempts with firearms (Rate Ratio=12.7) and assault by striking (Rate
      Ratio=8.9). Alcohol was noted on the record of 37.5% of Alaska Native injuries
      and 15.5% of Alaska White injuries. Alcohol was involved in 60.8% of intentional
      injuries involving Alaska Natives and 27.1% for Alaska Whites.

PMID- 15565831
TI  - [Cardioembolic stroke].

PMID- 15565832
TI  - [Secondary prevention of stroke].

PMID- 15565833
TI  - [Influence of smoking on the cerebral hemodynamics and biochemical blood indices
      in chronic insufficiency of brain circulation].
AB  - The influence of smoking on cerebral hemodynamics and biochemical blood indices
      has been studied in 50 male patients with chronic insufficiency of brain
      circulation (CIBC), aged 40-50 years, divided into 2 groups: smoking (n=26) and
      nonsmoking (n=24). Smoking was shown to play a substantial role in the
      development of discirculatory encephalopathy with atrophic brain changes, causing
      metabolic disturbances (a shift of acid-basic balance towards acidosis) and
      microcirculation disorders due to altered cerebrovascular reactivity. These
      alterations develop previously to hemodynamically significant atherosclerotic
      arteries lesion and emerge irrespective of the presence of atherosclerotic
      vascular changes, atherogenic shifts of lipid metabolism, disturbances of free
      radical processes and platelet aggregation.

PMID- 15565834
TI  - [Lacunar stroke and subcortical arteriosclerotic encephalopathy].
AB  - Clinical and neurovisual features were compared in 2 groups of patients who have
      survived the first lacunar stroke (LS). Group 1 included 35 patients (mean age
      59.6 +/- 7.1 years), in stable state for 5.7 +/- 2.5 years; group 2 consisted of
      39 patients (mean age 58.1 +/- 8.1 years) with LS as a debut of subcortical
      arteriosclerotic encephalopathy (SAE), illness duration after LS development--3.9
      +/- 2.9 years. Several parameters revealed statistically significant between
      group differences: "classical" lacunar syndromes, most frequently motor
      hemiparesis, were detected in 94% of group 1 patients and in 42% of group 2
      patients. Pareses of the extremities were marked or moderate in 57% and 3% of the
      patients, respectively. Foci characteristic of LS were determined by MRI/CT in
      all the patients of group 1 and in 69% of the patients of group 2. Foci mean size
      (MRI, regime T1) was larger in group 1 (0.24 +/- 0.18 cm3), comparing to group 2
      (0.11 +/- 0.06 cm3); foci shape was round or oval in 77% of patients in group 1
      and irregular--in 51% of patients in group 2. In group 1, concomitant
      asymptomatic leucoareosis and lacunes were detected in 37% and 20%; in group 2-
      in 77% and 62%, respectively. The differences revealed may be used in prognosis
      of LS further course. These differences may be underlied by the lesions of
      intracerebral arteries of different size and differend of change occurrence that,
      to a certain extent, relate to different hemodynamic variants of arterial
      hypertension.

PMID- 15565835
TI  - [Cerebellum hemorrhages and infarctions: clinical computed tomography study].
AB  - A complex examination of 46 patients with acute disturbances of cerebral
      circulation in the cerebellum was carried out. A new volumetric coefficient of
      this area lesion is proposed. The variants of the clinical course of cerebellum
      hemorrhage and infarctions in respect to the coefficient's value were
      distinguished. The course is considered favorable if the values are less than
      0.08. The higher values indicate, as a rule, a progressive increase of
      neurological symptoms up to a lethal outcome. The results reveal that the
      volumetric coefficient of the cerebellum lesion is a reliable parameter both for
      prognosis and for quantitative evaluation of acute vascular processes in the
      cerebellum, allowing taking into account the potentials of reserve intracranial
      space of the posterior cranial focca as well as individual peculiarities of brain
      and cranial sizes.

PMID- 15565836
TI  - [Free radicals in cerebral ischemia].
AB  - The review considers an involvement of active oxygen forms, nitric oxide (NO) and
      its active forms in accumulation of low molecular weight cytotoxic compounds that
      lead directly to cell death. A dual role of free radicals in cerebral ischemia,
      free radical function as secondary messengers are analysed.

PMID- 15565837
TI  - [Blood cell aggregation and oxidative stress in pathogenesis of ischemic stroke].
AB  - Rheologic properties of blood cells and a state of oxidative-reductive processes
      and blood systems have been studied in 75 patients in acute period of ischemic
      stroke. The signs of oxidative stress development and simultaneous augmentation
      of blood cells aggregation were found. Shifts of redox-equilibrium in thiol
      disulfide and ascorbate oxidative-reductive blood systems and cells aggregation
      dependence on their state were detected. An interrelation of oxidative processes
      and blood cells aggregation with clinical course severity and outcome was
      revealed. The authors discuss possible mechanisms for blood cells aggregation in
      oxidative stress. Including of antioxidants in the pathogenetic therapy and their
      earlier usage reduce essentially the intensity of oxidative stress and blood
      cells aggregation and promote neurological symptoms regress. The results obtained
      allow considering antioxidant treatment as a pathogenic modality for prevention
      and treatment of ischemic stroke. Clinico-laboratory correlations suggest a
      pathogenic role of oxidative stress in ischemic stroke as a factor augmenting
      aggregation processes and promoting intravascular thrombogenesis.

PMID- 15565838
TI  - [Cryoglobulinemia and extracorporal plasma therapy in severe ischemic stroke].
AB  - Forty-five patients with carotid ischemic stroke have been examined within the
      first 24 hours from the disease onset. The Orgogozo and NIH scales were used to
      objectify a severity of the patient's state and the Barthel scale--to evaluate a
      degree of functional rehabilitation. Cryoglobulins (CG) were measured in blood
      serum by spectrophotometric method on the 1st, 2nd, 3rd, 7th and 21st days.
      Selective plasmapheresis was included in the therapeutic complex for 22 randomly
      selected patients. In both groups, a level of CG positively correlated with a
      severity of the patient's state on the 1st day of the monitoring (r=-0.5;
      p<0.01). The study of hemostasis indicated the presence of a direct correlation
      between an increase of platelet aggregation, blood hyperviscosity and CG
      concentration (r=0.46; p<0.05 and r=0.74; p<0.01, respectively). Higher scoring
      on the Orgogozo scale and Barthel scale prevailed in the group treated with
      plasmapheresis that significantly correlated with a decrease in CG concentration
      in blood serum (r=-0.6; p<0.05 and r=0.5; p<0.05 respectively). An evaluation of
      platelet aggregation, blood viscosity and a coagulogram on the 21st day of the
      disease revealed a significant improvement of blood rheology in the group of
      patients switched to efferent therapy.

PMID- 15565839
TI  - [Functional characteristics of gait and standing posture in poststroke patients
      in residual period].
AB  - Using biomechanic method, gait and standing posture were studied in 17 stroke
      patients in a remote poststroke period. The locomotor system was found to have
      non-specific compensatory changes to optimize motor functions and reduce
      functional disturbances. Symptoms of the triceps surae muscle insufficiency as
      well as a balance deficit at standing posture and displacement of the center of
      pressure towards the non-affected side were characteristic of the given stage of
      rehabilitation stroke period that should be taken into account during the
      rehabilitation treatment.

PMID- 15565840
TI  - [Use of sodium succinate in complex treatment of ischemic stroke].
AB  - The results of the study of sodium succinate efficacy in the treatment of 60
      patients with ischemic stroke in comparison to the control group, not receiving
      antioxidants, are presented. The best results of sodium succinate were achieved
      in regress of local and general brain symptoms. The authors emphasize a
      possibility of the treatment at home and in outpatient clinic as well as cheaper
      price of sodium succinate versus other succinates.

PMID- 15565841
TI  - [Aspirin in the treatment and prevention of stroke].

PMID- 15565842
TI  - [Long-term survival of poststroke patients and problem of the cardiovascular risk
      factors control according to the data of Krasnodar stroke register].
AB  - Out of 254 patients included in Krasnodar stroke register in the last half-year
      of 1997, 48.8% survived one year, 26.8% were alive by June 2003 and 5.5% have
      left the region. A dynamics of the prevalence of the risk factors for secondary
      stroke during 5.7 +/- 0.2 years indicated a significant increase of
      cardiovascular system lesion. However, the corrective means of major modifying
      cardiovascular risk factors substantially differed from those recommended by the
      results of large randomized clinical studies conducted over the last years. Use
      of detected reserves of secondary prophylaxis in patients who survived stroke is
      restricted by organizational and economic problems.

PMID- 15565843
TI  - [Can the number of people killed in traffic accidents in Denmark be reduced?].

PMID- 15565844
TI  - [Childhood and juvenile absence epilepsy. Treatment and prognosis].

PMID- 15565845
TI  - [Benign partial epilepsy with centrotemporal spikes in children (Roland's
      epilepsy). Treatment and prognosis].

PMID- 15565846
TI  - [Benign occipital epilepsy in children].

PMID- 15565847
TI  - [Prevention of traffic accidents with the help of area-wide traffic calming].

PMID- 15565848
TI  - [High dose chemotherapy versus conventional chemotherapy in metastasing breast
      cancer. An analysis of a systematic Cochrane review].

PMID- 15565849
TI  - [High dose chemotherapy and autologous bone marrow or stem cell transplantation
      versus conventional chemotherapy in primary breast cancer. An analysis of a
      systematic Cochrane review].

PMID- 15565850
TI  - [Suicide among elderly in the county of Aarhus during the period 1993-2000. A
      descriptive study].

PMID- 15565851
TI  - [Stress among working population of Danes].

PMID- 15565852
TI  - [Treatment of blunt hepatic trauma. Introduction of non-surgical treatment].

PMID- 15565853
TI  - [Spasmus mutans in a nine-month-old infant].

PMID- 15565854
TI  - [Melorheostosis in a ten-year-old girl].

PMID- 15565855
TI  - [Spontaneous pneumomediastinum, a rare cause of chest pain].

PMID- 15565856
TI  - [Sepsis epidemiology in Norway and Denmark--a comment].

PMID- 15565857
TI  - [Smoking outside does not protect infants form tobacco smoke exposure].

PMID- 15565858
TI  - [Attitude to acupuncture--on account of a book].

PMID- 15565859
TI  - The convergence of cell transplantation and nanoengineering.

PMID- 15565860
TI  - Variation in human islet viability based on different membrane integrity stains.
AB  - Membrane integrity fluorescent staining is used routinely to evaluate islet
      viability. Results are used as one of the determining factors in islet product
      release criteria, and are used to assess the efficacy of different culture
      conditions. Recently, it has been observed that there is variation in the
      viability staining of freshly isolated islets based on which viability assay is
      used. This investigation compares three membrane integrity stains for the
      viability assessment of isolated human islets. Fluorescein diacetate/propidium
      iodide (FDA/ PI), the current standard method for assessing islet viability,
      demonstrates intense extracellular fluorescence, reducing the differential
      staining of intact islets. We further evaluated SYTO-13/ethidium bromide (SYTO/
      EB) and calcein AM/ethidium homodimer (C/EthD) as alternative viability assays,
      and found considerable variation between FDA/PI and either SYTO/EB or C/EthD
      staining. Preparations of human islets were obtained from cadaveric pancreata
      after collagenase digestion, mechanical separation, and purification by
      continuous Ficoll gradient centrifugation. For each preparation, two replicate
      samples of 50 islets were counted for each stain, and the percent viability
      calculated. The results for SYTO/EB and C/EthD were nearly identical [57.6 +/-
      7.3% and 57.9 +/- 7.2%, respectively (mean +/- SEM), N = 11]. FDA/PI-stained
      islets, however, showed consistently elevated values when compared to SYTO/EB.
      Accurate assessment of islet viability remains a critical determinant of islet
      product release. The discrepancies found between FDA/PI scoring and visual
      quality, compared with alternative stains, suggests that the FDA/PI stain may not
      be the optimal approach to assess islet viability.

PMID- 15565861
TI  - Retrovirally transferred genes inhibit apoptosis in an insulin-secreting cell
      line: implications for islet transplantation.
AB  - The transplantation of pancreatic islets for the treatment of type I diabetes is
      hindered by the enormous loss of cells due to early apoptotic events. Genetic
      engineering of islets with cytoprotective genes is an important strategy aimed to
      enhance the survival of these cells in the transplant setting. The present study
      was designed to evaluate and compare the effects of five genes on a cell line
      derived from insulin-producing beta-cells, NIT-1. Cells were transduced using a
      Maloney murine leukemia virus (MLV) vector coding for yellow fluorescent protein
      (YFP) and for one of the following antiapoptotic genes: cFLIP, FADD-DN, BcL-2, PI
      9, and ICAM-2. These genes were able to protect NIT-1 cells from cytokine-induced
      apoptosis to varying degrees ranging from no protection to significant protection
      equivalent to an optimal dose of a chemical caspase inhibitor. The data
      demonstrate that cFLIP, FADD-DN, and PI-9 are significantly more effective in
      protecting NIT-1 cells than BcL-2 and ICAM-2. Additionally, the data show that
      despite its weak in vitro inhibition of caspase-3, PI-9 affords significant
      protection against TNF-alpha-induced apoptosis in these cells. These genes may be
      ideal candidates to augment islet survival following transplantation.

PMID- 15565862
TI  - The use of multiparametric monitoring during islet cell isolation and culture: a
      potential tool for in-process corrections of critical physiological factors.
AB  - Variables such as pH, pCO2, and PO2 have been established in the literature as
      critical factors that could affect the outcome of the islet cell processing and,
      therefore, the quality of the cells that could be transplanted. This report
      describes a highly accurate continuous multiparametric monitoring system and its
      evaluation for continuous monitoring of physiological variables during critical
      steps of the islet isolation procedure as well as during in vitro culture of the
      insulin-producing cells. Close monitoring of these variables could be of
      assistance to improve the outcome of islet cell processing, allowing to identify
      as soon as possible problems that could be corrected during the procedure, as
      well as during in vitro preservation, or shipment to remote sites.

PMID- 15565863
TI  - The contribution of chemokines and chemokine receptors to the rejection of fetal
      proislet allografts.
AB  - Chemokines regulate the recruitment of leukocytes to sites of inflammation and
      may therefore play an important role in lymphocyte trafficking between draining
      lymph nodes and pancreatic islet tissue allografts. The intragraft expression of
      alpha- and beta-chemokine mRNA during the rejection of BALB/c proislet (fetal
      precursor islet tissue) allografts in CBA/H mice was assessed quantitatively and
      semiquantitatively by RT-PCR analyses. Allograft rejection was associated with
      the strongly enhanced (from day 4) and prolonged expression (up to day 10) of the
      alpha-chemokine IP-10 and enhanced intragraft mRNA expression of the beta
      chemokines MCP-1, MIP-lalpha, MIP-1beta, RANTES, and eotaxin. Peak transcript
      expression was identified at day 4 (IP-10, MCP-1), day 5 (eotaxin), day 6 (MIP
      1alpha, MIP-1beta), and day 14 (RANTES). To examine the role of beta-chemokine
      receptors in allograft rejection, additional allografts to CCR2-/- , CCR5-/-, and
      wild-type CCR+/+ mice were analyzed by histology, immunohistochemistry, and
      morphometry. In CCR5-/- mice, the intragraft recruitment of T cells and
      macrophages was slower and allograft destruction was delayed; in CCR2-/- mice,
      the initial entry of macrophages was retarded but graft survival was not
      prolonged. These findings suggest that IP-10 regulates the initial influx of T
      cells into proislet allografts, MCP-1/CCR2 signaling controls initial macrophage
      entry, and the MIP-1alpha, MIP-1beta, and RANTES/CCR5 pathway contributes to the
      rejection response by subsequently amplifying the recruitment of T cell
      subpopulations required for graft destruction.

PMID- 15565864
TI  - Factors influencing functional survival of microencapsulated islet grafts.
AB  - Graft function of encapsulated islets is restricted in spite of the fact that
      inflammatory responses against capsules are limited to a portion less than 10%.
      It has been shown that dysfunction is accompanied by a gradual decrease in the
      glucose-induced insulin response (GIIR), a hyperproliferation of islet cells, and
      gradual necrosis. Also, limited survival is associated with the presence of
      macrophages in the overgrowth. In the present study, we investigate whether
      macrophages are the inducers of dysfunction of encapsulated grafts. Four weeks
      after successful transplantation of microencapsulated rat allografts we
      determined the GIIR, the rate of islet cell replication, and islet cell death.
      Also, we quantified the number of macrophages on the overgrown capsules. This
      assessment was applied to set up an in vitro coculture system of macrophages and
      encapsulated islets. We retrieved 93 +/- 6.2% of the capsules of which 9.2 +/-
      0.3% was overgrown. The GIIR of the retrieved nonovergrown islets was reduced
      when compared with freshly encapsulated islets. The replication rate of the
      retrieved islet cells was eightfold higher than in the normal pancreas. Apoptosis
      was rarely observed but 37 +/- 4% of the total islet surface was composed of
      necrosis. We found a mean of 1542 +/- 217 macrophages per capsule. Coculture of
      1500 NR8383 macrophages per encapsulated islets induced a substantial reduction
      in GIIR but a decrease instead of increase in replication. Necrosis was
      restricted to 13 +/- 1.3% of the islet cells and was not increased by the
      presence of macrophages. Our observations indicate that we should focus on
      reduction of macrophage activation and on improving the nutrition of encapsulated
      islets to prevent islet cell death.

PMID- 15565865
TI  - Comparison of fetal porcine aggregates of purified beta-cells versus islet-like
      cell clusters as a treatment of diabetes.
AB  - Fetal pig islet-like cell clusters (ICCs) have the potential to reverse diabetes
      1-5 months after transplantation. In a fetal ICC, however, beta-cells constitute
      only 6-8% of the cells, in contrast to 65% in an adult pig islet. Attempts to
      purify fetal beta-cells from cell clusters and compare their function to that of
      ICCs have not been shown previously. Beta-cells were purified from ICCs isolated
      from the fetal pig pancreas. These were then aggregated and maintained in culture
      for 3 days. ICCs were isolated from fetal pig pancreas and allowed to round up in
      culture for 3 days. Transplantation of aggregates and ICCs (10,000 and 12,600,
      respectively) into diabetic immunoincompetent mice resulted in normoglycemia at
      18 +/- 2 and 8 +/- 1 weeks, respectively (p = 0.0006). Removal of grafts after
      normalization of blood glucose levels resulted in rapid return of hyperglycemia
      in both groups. In conclusion, a purified population of immature beta-cells can
      be produced from the fetal pig pancreas. The reason these cells take longer than
      ICCs to reverse diabetes when transplanted is postulated to be because of the
      relative lack of precursor cells from which beta-cells differentiate. This
      finding may have implications for stem cell therapy, as other cell types, other
      than purified beta-cells, may be necessary for appropriate function in vivo.

PMID- 15565867
TI  - Photofabricated gelatin-based nerve conduits: nerve tissue regeneration
      potentials.
AB  - There is a strong demand for development of nerve guide conduit with prompt nerve
      regeneration potential for injury-induced nerve defect. Prior to study on nerve
      tissue engineering using Schwann cells or nerve stem cells, the effectiveness of
      photofabricated scaffolds based on photocurable gelatin was examined. This study
      describes the evaluation of in vivo nerve tissue regeneration potentials of three
      custom-designed and -fabricated prostheses (inner diameter, 1.2 mm; outer
      diameter, 2.4 mm; wall thickness, 0.60 mm; and length, 15 mm) made of photocured
      gelatin: a plain photocured gelatin tube (model I), a photocured gelatin tube
      packed with bioactive substances (laminin, fibronectin, and nerve growth factor)
      coimmobilized in a photocured gelatin rod (model II), and a photocured gelatin
      tube packed with bioactive substances coimmobilized in multifilament fibers
      (model III). These prostheses were implanted between the proximal and distal
      stumps 10 mm of the dissected right sciatic nerve of 70 adult male Lewis rats for
      up to 1 year. The highest regenerative potentials were found using the model III
      prosthesis, followed by the model II prosthesis. Markedly retarded neural
      regeneration was observed using the model I prosthesis. These were evaluated from
      the viewpoints of functional recovery, electrophysiological responses, and tissue
      morphological regeneration. The significance of the synergistic cooperative
      functions of multifilaments, which serve as a platform that provides contact
      guidance to direct longitudinal cell movement and tissue ingrowth and as a cell
      adhesive matrix with high surface area, and immobilized bioactive substances,
      which enhance nerve regeneration via biological stimulation, is discussed.

PMID- 15565866
TI  - Studies on the differentiation of dopaminergic traits in human neural progenitor
      cells in vitro and in vivo.
AB  - The development of cell replacement therapies for the treatment of
      neurodegenerative disorders such as Parkinson's disease (PD) may depend upon the
      successful differentiation of human neural stem/progenitor cells into dopamine
      (DA) neurons. We show here that primary human neural progenitors (HNPs) can be
      expanded and maintained in culture both as neurospheres (NSPs) and attached
      monolayers where they develop into neurons and glia. When transplanted into the 6
      hydroxydopamine-lesioned rat striatum, undifferentiated NSPs survive longer (60%
      graft survival at 8-16 weeks vs. 30% graft survival at 8-13 weeks) and migrate
      farther than their attached counterparts. While both NSP and attached cells
      continue to express neuronal traits after transplantation, the spontaneous
      expression of differentiated transmitter-related traits is not observed in either
      cell type. However, following predifferentiation in culture using a previously
      described cocktail of reagents, approximately 25% of HNPs can permanently express
      the DA enzyme tyrosine hydroxylase (TH), even following replating and removal of
      the DA differentiation cocktail. When these predifferentiated HNPs are
      transplanted into the brain, however, TH staining is not observed, either because
      expression is lost or TH-expressing cells preferentially die. Consistent with the
      latter view is a decrease in total cell survival and migration, and an enhanced
      glial response in these grafts. In contrast, we found that the overall survival
      of HNPs is improved when cells engraft near blood vessels or CSF compartments or
      when they are placed into an intact unlesioned brain, suggesting that there are
      factors, as yet unidentified, that can better support the development of
      engrafted HNPs.

PMID- 15565868
TI  - Efficient early and sustained transduction of human fetal mesencephalon using
      adeno-associated virus type 2 vectors.
AB  - The success of transplantation of human fetal mesencephalic tissue into the
      putamen of patients with Parkinson's disease (PD) is still limited by the poor
      survival of the graft. In animal models of fetal transplantation for PD,
      antiapoptotic agents, such as growth factors or caspase inhibitors, or agents
      counteracting oxidative stress enhance the survival and reinnervation potential
      of the graft. Genetic modification of the transplant could allow a local and
      continuous delivery of these factors at physiologically relevant doses. The major
      challenge remains the development of strategies to achieve both early and
      sustained gene delivery in the absence of vector-mediated toxicity. We recently
      reported that E14 rat fetal mesencephalon could be efficiently tranduced by adeno
      associated virus type 2 (AAV2) vectors and that gene expression was maintained
      until at least 3 months after transplantation in the adult rat striatum. Here we
      report that an AAV2 vector can mediate the expression of the EGFP reporter gene
      under the control of a CMV promoter in organotypic cultures of freshly explanted
      solid fragments of human fetal mesencephalic tissue as early as 3 days to at
      least 6 weeks postinfection. These results suggest that AAV2 vectors could be
      used to genetically modify the human fetal tissue prior to transplantation to
      Parkinson's patients to promote graft survival and integration.

PMID- 15565869
TI  - In vivo evaluation of pharmacologically active microcarriers releasing nerve
      growth factor and conveying PC12 cells.
AB  - Cell therapy will probably become a major therapeutic strategy in the coming
      years. Nevertheless, few cells survive transplantation when employed as a
      treatment for neuronal disorders. To address this problem, we have developed a
      new tool, the pharmacologically active microcarriers (PAM). PAM are biocompatible
      and biodegradable microparticles coated with cell adhesion molecules, conveying
      cells on their surface and presenting a controlled delivery of growth factor.
      Thus, the combined effect of growth factor and coating influences the transported
      cells by promoting their survival and differentiation and favoring their
      integration in the host tissue after their complete degradation. Furthermore, the
      released factor may also influence the microenvironment. In this study, we
      evaluated their efficacy using nerve growth factor (NGF)-releasing PAM and PC12
      cells, in a Parkinson's disease paradigm. After implantation of NGF-releasing or
      unloaded PAM conveying PC12 cells, or PC12 cells alone, we studied cell survival,
      differentiation, and apoptosis, as well as behavior of the treated rats. We
      observed that the NGF-releasing PAM coated with two synthetic peptides (poly-D
      lysine and fibronectin-like) induced PC12 cell differentiation and reduced cell
      death and proliferation. Moreover, the animals receiving this implant presented
      an improved amphetamine-induced rotational behavior. These findings indicate that
      PAM could be a promising strategy for cell therapy of neurological diseases and
      could be employed in other situations with fetal cell transplants or with stem
      cells.

PMID- 15565870
TI  - The transfer of ocular cells using collagen.
AB  - The present study was designed to evaluate the use of collagen gel loaded with
      human retinal pigment epithelium (ARPE19) in cellular transfer and to assess its
      viability within the gel. Collagen solution was prepared by dissolving calfskin
      in hydrochloric acid to make a final concentration of 2.0 mg/ml and this was
      mixed with 10,000 ARPE19 cells/ml. The cell viability in gel was determined using
      MTT assay. van Gieson stain and proliferating cell nuclear antigen (PCNA) were
      used to identify the location of collagen and to localize the site of cell
      proliferation, respectively. The ARPE19 cells in gel appeared to be healthy with
      a rounded morphology. The optimal collagen concentration was 1.9 mg/ml. When this
      concentration was used to hold cells for over 12 days, it could be seen that the
      growth rate was the same between day 2 and day 8 in gel and on plastic. When the
      cell-loaded gels were transferred onto standard tissue culture plastics,
      progressive cell migrations over time resembling cell migrations in organotypic
      explant cultures were observed. Upon intravitreal injection of cell-containing
      collagen suspension into a rabbit's eye, the gel became suspended within the
      vitreous a few hours after injection (day 0). However, it became obvious that the
      gel dispersed and spread around the vitreous even after just 24 h. These cells
      inside the vitreous were PCNA positive, indicating that the human ARPE19 cells
      have the capacity to proliferate even after 11 days. The present study
      demonstrated the potential use of collagen gel as a tool in the transfer of
      cellular matrix onto other substrates. The results show that the cell seeding
      number must be critically balanced with the concentration of gel for it to be
      used as transplant material.

PMID- 15565871
TI  - Autologous bone marrow stromal cell transplantation for repair of full-thickness
      articular cartilage defects in human patellae: two case reports.
AB  - This study assessed the effectiveness of autologous bone marrow stromal cell
      transplantation for the repair of full-thickness articular cartilage defects in
      the patellae of a 26-year-old female and a 44-year-old male. These two patients
      presented in our clinic because their knee pain prevented them from walking
      normally. After thorough examination, we concluded that the knee pain was due to
      the injured articular cartilage and decided to repair the defect with bone marrow
      stromal cell transplantation. Three weeks before transplantation, bone marrow was
      aspirated from the iliac crest of each patient. After erythrocytes had been
      removed by use of dextran, the remaining nucleated cells were placed in culture.
      When the attached cells reached subconfluence, they were passaged to expand in
      culture. Adherent cells were subsequently collected, embedded in a collagen gel,
      transplanted into the articular cartilage defect in the patellae, and covered
      with autologous periosteum. Six months after transplantation, clinical symptoms
      (pain and walking ability) had improved significantly and the improvement has
      remained in effect (5 years and 9 months posttransplantation in one case, and 4
      years in the other), and both patients have been satisfied with the outcome. As
      early as 2 months after transplantation, the defects were covered with tissue
      that showed slight metachromatic staining. Two years after the first and 1 year
      after the second transplantation, arthroscopy was performed and the defects were
      repaired with fibrocartilage. Results indicate autologous bone marrow stromal
      cell transplantation is an effective approach in promoting the repair of
      articular cartilage defects.

PMID- 15565872
TI  - The nuclear envelope: a comparative overview.

PMID- 15565873
TI  - The nuclear envelope proteome.

PMID- 15565874
TI  - Nuclear envelope proteins and human disease.

PMID- 15565875
TI  - Protein interactions, right or wrong, in Emery-Dreifuss muscular dystrophy.

PMID- 15565876
TI  - Plant nuclear envelope proteins.
AB  - Compared to research in the animal field, the plant NE has been clearly under
      investigated. The available data so far indicate similarities as well as striking
      differences that raise interesting questions about the function and evolution of
      the NE in different kingdoms. Despite a seemingly similar structure and
      organization of the NE, many of the proteins that are integral components of the
      animal NE appear to lack homologues in plant cells. The sequencing of the
      Arabidopsis genome has not led to the identification of homologues of animal NE
      components, but has indicated that the plant NE must have a distinct protein
      composition different from that found in metazoan cells. Besides providing a
      selective barrier between the nucleoplasm and the cytoplasm, the plant NE
      functions as a scaffold for chromatin but the scaffolding components are not
      identical to those found in animal cells. The NE comprises an MTOC in higher
      plant cells, a striking difference to the organization of microtubule nucleation
      in other eukaryotic cells. Nuclear pores are present in the plant NE, but
      identifiable orthologues of most animal and yeast nucleoporins are presently
      lacking. The transport pathway through the nuclear pores via the action of
      karyopherins and the Ran cycle is conserved in plant cells. Interestingly, RanGAP
      is sequestered to the NE in plant cells and animal cells, yet the targeting
      domains and mechanisms of attachment are different between the two kingdoms. At
      present, only a few proteins localized at the plant NE have been identified
      molecularly. Future research will have to expand the list of known protein
      components involved in building a functional plant NE.

PMID- 15565877
TI  - Structure, function and assembly of the nuclear pore complex.

PMID- 15565878
TI  - Import and export at the nuclear envelope.
AB  - Eukaryotic cells transport a myriad of molecules between the nucleus and
      cytoplasm and have evolved a number of related biochemical pathways to achieve
      this, many of which have been elucidated in recent years. One central and common
      component to all the pathways is the NPC. NPC components appear to play vital
      roles in transport and the NPC is structurally dynamic, but whether its role is
      as a facilitator, a controller or both is yet to be decided and awaits further
      analysis on the role of individual components in specific pathways.

PMID- 15565879
TI  - Regulating gene expression in mammalian cells: how nuclear architecture
      influences mRNA synthesis and export to the cytoplasm.

PMID- 15565880
TI  - Nuclear shuttling in plant cells.

PMID- 15565881
TI  - Dynamics of nuclear lamina assembly and disassembly.
AB  - What can be concluded about lamin dynamics? a. While the nuclear lamina forms a
      tight network of proteins, individual lamina members, such as the lamin C
      proteins, are only partially bound to the lamina. b. A prominent pool of
      nucleoplasmic lamins exists in most cells, which interacts with intranuclear
      structures (DNA? Histones? Replication and/or transcription complexes?) in a
      dynamic fashion. c. During mitosis lamins do not play a key role in the initial
      reformation of the nuclear envelope. However, they are important for the correct
      functioning of the nucleus immediately after mitosis. Many questions remain
      unanswered, although nuclear lamins have been studied at different levels for
      over 20 years. We have only just begun to understand their crucial role in
      several cellular processes. Some of the important questions that still remain
      are: a. The function of intranuclear lamin foci. Are these native nuclear
      structures (nuclear channels/tubules) and do they play a role in replication and
      transcription? b. The function of the nucleoplasmic veil of lamins. Are these
      molecules only temporarily bound to intranuclear structures as a result of
      affinity to chromosomes or nuclear proteins, or is there a functional interaction
      with these molecules? c. The extent to which lamin molecules add to nuclear
      membrane organisation. Do these molecules play a key role in keeping the membrane
      intact and the nucleus functional, or are they only one of many supportive
      component of the nuclear membrane?

PMID- 15565882
TI  - Spatial and temporal control of nuclear envelope assembly by Ran GTPase.
AB  - Using evidence derived primarily from studies using Xenopus egg extracts, a model
      for the role of Ran in multiple stages during NE assembly can be proposed (Figure
      2). Ran is concentrated on chromatin prior to NE assembly and recruits RCC1 that
      generates Ran-GTP locally. Recruitment of RCC1 to chromatin may be a specialized
      mechanism to initiate NE assembly following fertilization of the egg, whereas in
      somatic cells, RCC1 may be present on chromatin throughout mitosis. Ran-GTP
      recruits vesicles to the surface of chromatin, and promotes vesicle fusion to
      form the double membrane of the NE. Ran-GTP may recruit membrane vesicles to
      chromatin through binding to integral membrane proteins through importin-beta. A
      transient complex would be formed between Ran-GTP, importin-beta and the target
      protein, which would be released locally to promote assembly of a precursor
      complex. GTP hydrolysis by Ran would release importin-beta, but may also play a
      role in vesicle fusion. Ran-GTP also promotes NPC assembly by releasing
      nucleoporins such as Nup107 from inhibitory complexes with importin-beta. In
      vertebrate cells undergoing mitosis, the majority of Ran molecules are excluded
      from the chromosomes and dispersed into the cytoplasm. Relocalization of Ran to
      chromatin at the end of mitosis may co-ordinate the initiation of NE assembly
      with disassembly of the mitotic spindle. The function of Ran in this transition
      is likely to be coupled to changes in the activity of cyclin-dependent protein
      kinases and other activities that control the progression of the cell cycle.
      Thus, changes in the localization of Ran and its regulators provide temporal and
      spatial control of NE assembly at the end of mitosis.

PMID- 15565883
TI  - Nuclear envelope dynamics during mitosis.

PMID- 15565884
TI  - Nuclear dynamics in higher plants.

PMID- 15565885
TI  - The nuclear envelope in the plant cell cycle.

PMID- 15565886
TI  - Signalling to the nucleus via A-kinase anchoring proteins.
AB  - The cell nucleus is a highly dynamic organelle whose function and structure
      during the cell cycle is tightly controlled. A number of signals triggered by
      external stimuli or intracellular clocks are relayed to the nucleus by protein
      kinases and phosphatases. Specificity of action of kinases and phosphatases can
      be achieved by their recruitment into multiprotein complexes targeted to discrete
      subcellular or subnuclear loci. One class of molecules targeting signalling units
      within single complexes are A-kinase anchoring proteins or AKAPs. AKAPs not only
      target enzymes to their substrate but may also regulate enzyme activity. This
      chapter highlights the role of nuclear AKAPs in relaying and modulating protein
      kinase and phosphatase signals to the nucleus or chromosomes.

PMID- 15565887
TI  - Spectraplakins and nesprins, giant spectrin repeat proteins participating in the
      organization of the cytoskeleton and the nuclear envelope.

PMID- 15565888
TI  - Arabidopsis U1 snRNP 70K protein and its interacting proteins: nuclear
      localization and in vivo dynamics of a novel plant-specific serine/arginine-rich
      protein.

PMID- 15565889
TI  - Calcium/calmodulin-binding transcription activators in plants and animals.

PMID- 15565890
TI  - CAAX-dependent modifications of the lamin proteins in the organization of the
      nuclear periphery.

PMID- 15565891
TI  - All in the family: evidence for four new LEM-domain proteins Lem2 (NET-25), Lem3,
      Lem4 and Lem5 in the human genome.
AB  - LEM-domain proteins share a folded structure, the 'LEM-domain', which binds a
      conserved chromatin protein named BAF. Most LEM-domain proteins are found at the
      nuclear membrane, but some are nucleoplasmic. All characterized members of this
      family bind nuclear lamin filaments. We summarize the 'founding' LEM-domain
      proteins LAP2, emerin and MAN1 ('SANE' or 'XMAN' in Xenopus) and their emerging
      roles in gene regulation and nuclear assembly. These roles are placed in the
      context of human diseases ('laminopathies') caused by mutations in either emerin
      or A-type lamins. Other LEM-domain proteins might modify the phenotype or
      severity of human laminopathy, or cause new laminopathies. We summarize evidence
      that the human genome encodes at least four additional LEM-domain proteins,
      designated Lem2 (NET-25), Lem3, Lem4 and Lem5. Early adaptation of a consistent
      nomenclature, such as the "Lem" names proposed here, will facilitate rapid
      progress in this field. Further investigation of 'founder' and novel members of
      this family will be important to understand nuclear structure, and presents new
      opportunities to understand human disease.

PMID- 15565892
TI  - [Access to help for emotionally disabled children and adolescents must be
      continued].

PMID- 15565893
TI  - [Does a morning dose of Methylphenidate Retard reduce hyperkinetic symptoms in
      the afternoon?].
AB  - OBJECTIVES: In order to treat children with Attention-deficit/Hyperactivity
      Disorder (ADHD) with a once-a-day stimulant several galenic approaches have been
      tried. The long acting methylphenidate (MPH, Medikinet-Retard) is a preparation
      with a two-step dynamic to release MPH (step one: acute; step two: prolonged).
      The efficacy of Medikinet-Retard, a new long-acting methylphenidate preparation,
      is analyzed based on the assessment of parents in the afternoon. METHODS: In a
      multicenter drug treatment study (placebo controlled, randomized, double-blind)
      85 children (normal intelligence, age 6 to 16 years, diagnosis of ADHD according
      to DSM-IV) were investigated over 4 weeks with weekly visits. Forty-three
      children received Medikinet-Retard and forty-two children placebo. The weekly
      dose titration depending on body weight and symptomatology allowed a final
      maximum of 60 mg. The effects on ADHD as perveived by the parents were assessed
      weekly with a German symptom checklist for ADHD according to DSM-IV and ICD-10
      (FBB-HKS). The differences between baseline and last week of treatment were
      compared statistically between groups. RESULTS: There was a large and
      statistically significant positive drug effect on ADHD symptomatology. The effect
      size of these differences was d = 1.2 (total score). Effects were found on
      inattention, hyperactivity and impulsity on the respective subscales. The
      efficacy of Medikinet-Retard was evaluated by the parents on an average as good.
      The rate of responders was four-times higher in the verum-group. The correlations
      of the changed scores in the parent ratings with the respective change scores in
      the teacher ratings were in the medium range. CONCLUSION: This is the first study
      with a German long-acting methylphenidate preparation (Medikinet-Retard).
      According to data based on parents' assessments, the drug showed very good
      clinical efficacy and safety in children with ADHD. Its two step galenic release
      of methylphenidate seems to be appropriate for a once-a-day (morning) stimulant
      in schoolchildren.

PMID- 15565894
TI  - [Rating and standardisation of pictures from the International Affective Picture
      System appropriated for children. Examination of children in a field sample aged
      six to twelve years].
AB  - OBJECTIVE: The aim of this study was to validate and standardise a number of
      pictures from the International Affective Picture System from Lang (CSEA-NIMH,
      1999; Lang et al., 1999) relative to arousal and valence in 57 boys and 63 girls
      aged between six and twelve years. METHOD: 18 pictures with six positive, six
      negative and six neutral stimuli were presented to children aged between six and
      twelve years. The children had to rate the pictures with regard to the dimensions
      valence and arousal using the Self-Assessment-Manikin (SAM; Lang et at., 1980;
      Bradley et al., 1994), a visual rating scale. RESULTS: Children aged between six
      and twelve years were able to discriminate pictures and to rate them according to
      the two basic dimensions of emotion valence and arousal. CONCLUSIONS: Our
      selection of pictures from Lang's International Affective Picture System provides
      a number of standardised stimuli, which are suitable for affect induction for
      example in psychophysiological and neuroimaging studies in the age group of
      children between six and twelve years.

PMID- 15565895
TI  - [Therapy of tic-disorders].
AB  - BACKGROUND: Within the last decade therapeutic approaches to tic disorders are
      reflected in many new studies. The advent of novel neuroleptics and the more
      sophisticated behavioural therapeutic techniques may give new hope to children
      and adolescents with tic disorders. OBJECTIVE: Hence, the progress in the field
      should be explored to find out the state of the art. METHOD: A critical review of
      the empirically based literature and practical experience. RESULTS: Worldwide,
      drug treatment with clonidine and (from the group of novel antipsychotics)
      risperidone show the broadest empirical basis while in Europe benzamides have a
      good empirical clinical background. Behaviour therapy presents more and more
      helpful empirical data. CONCLUSIONS: Risperidone may become the first-line drug
      in treatment of tic disorders and behaviour therapy might be increasingly used
      within a multimodal treatment program.

PMID- 15565896
TI  - [The effectiveness of stimulants of retard forms in children and adolescents with
      ADHD--a systematic overview].
AB  - Stimulants are the matter of choice to treat attention deficit/hyperactivity
      disorder (ADHD) pharmacologically. The period of effectiveness of immediate
      release stimulants is, however, often not satisfying. Currently a variety of
      retarded forms of methylphenidate and also amphetamine were developed in order to
      minimize the problems involved in a daily dose. This paper presents the clinical
      studies on effectiveness, period of effectiveness and the profile of side effects
      of different forms of stimulants. In the clinical practice the new retard
      products are effective alternatives. There is an advantage in giving this drug in
      a once daily single dose. At the same time, the side effects that are caused by
      an extended period of being effective have to be studied in detail. A more exact
      adaptation to the requirements of daily obligations and needs of children and
      adolescents is difficult to realize. Future research is supposed to test schemes
      of titration including immediate and sustained released stimulants.

PMID- 15565897
TI  - [Paroxetine versus clomipramine in female adolescents suffering from anorexia
      nervosa and depressive episode--a retrospective study on tolerability, reasons
      for discontinuing the antidepressive treatment and different outcome
      measurements].
AB  - OBJECTIVES: So far, there have only been few studies concerning the question of
      indication and efficacy of antidepressive medication in children and adolescents
      with anorexia nervosa and depressive episode in the course of an inpatient
      treatment. In addition, there is a lack of studies comparing the tolerability and
      efficacy of different antidepressants given to anorectic patients of this
      particular age group. This study compares paroxetine, a specific SRI, with
      clomipramine, a TCA with SRI activity, concerning the frequency and quality of
      adverse side effects, the frequency and the reasons for discontinuating the
      antidepressive treatment and different outcome measurements. METHODS: 83 female
      patients, aged 10.9 to 18.1 years, who underwent an inpatient treatment at the
      Departement of Child and Adolescent Psychiatry and Psychotherapy at the
      University of Wuerzburg, Germany, were enrolled in this retrospective study. All
      of them met the ICD-10 criteria for anorexia nervosa and depressive episode and
      received an antidepressant medication with clomipramine or paroxetine. We
      collected data from basic documentation, treatment reports, and the multiaxial
      classification (MAS). Outcome measurements were the duration of treatment (days)
      and the increase of body weight (kg/m2). RESULTS: The discontinuation of the
      antidepressive treatment due to adverse side effects or a lack of efficacy was
      significantly more frequent with clomipramine than paroxetine (33.3 vs. 15.4%).
      The increase of body weight (2.8 vs. 2.6 kg/m2) was similar in both groups, but
      the duration of treatment was significantly shorter under paroxetine (71.9 vs.
      96.5 days). CONCLUSIONS: A shorter duration of treatment, faster increase of body
      weight, lower percentage of dicontinuating the antidepressive medication and last
      but not least economic reasons lead to the conclusion, that paroxetine should be
      preferred in female adolescents with anorexia nervosa and depressive episode.
      However, prospective studies are needed to confirm our findings.

PMID- 15565898
TI  - [Management of nosocomial infection in perioperative phase].

PMID- 15565899
TI  - [Perioperative nosocomial infection preventive measures].
AB  - For the prevention of perioperative nosocomial infection, 1) topical mupirocin
      treatment, 2) tight perioperative glycemic control and 3) immunonutrition are
      described. A large, prospective, randomized trial showed that the nasal
      application of mupirocin may effectively reduce postoperative Staphylococcus
      aureus nosocomial infection in the subgroup of patients who had S. aureus in
      their nares. Tight glycemic control after surgery, especially in the early period
      after operation, may also be effective in decreasing postoperative infection. In
      septic ICU patients, strict glycemic control even reduces ICU and hospital
      mortality rates. Several specific nutritional substrates such as arginine, omega
      3 fatty acids, glutamine, and RNA have been shown to modulate host immune
      function. Some enteral formulas enriched with such immunonutrients have been
      commercially available in the USA and in Europe and are now available in Japan.
      Recent meta-analyses of randomized, controlled trials have shown that the
      administration of these formulas to elective surgical patients results in a
      significant reduction in the risk of developing infectious complications by
      approximately 50% and shortens the overall hospital stay.

PMID- 15565900
TI  - [Hand disinfection and cross-infection countermeasures].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) causes droplet infection and
      contact infection, and therefore when taking measures against cross-infection it
      is preferable to take even stricter action than for other bacteria. The basic
      policies for preventing cross-infection require measures that assume the presence
      of MRSA until the results of bacterial testing are reported if discharge from the
      patient is noted. To prevent cross-infection, it is not sufficient simply to
      enforce strict disinfecting of the hands. It is necessary to establish a manual
      of measures to deal with situations at different posts.

PMID- 15565901
TI  - [Management of intravascular catheters for prevention of perioperative cross
      infections].
AB  - Bloodstream infection derived from an intravascular catheter occupies an
      important position among the various types of nosocomial infection. It is
      therefore necessary to establish a system for preventing catheter infection not
      only as measures for each separate infection, but also for the entire hospital.
      Catheter infections are mainly caused by contamination of the connecting part of
      a transfusion line during the infusion of drug solution as well as by
      contamination of the part of the catheter inserted. Consequently, the greatest
      possible care should be taken in the preparation of aseptic transfusion and the
      prevention of contamination when connecting a transfusion line. In particular,
      there are problems with three-way stopcocks, management of hubs, frequency of
      transfusion line exchange, fat emulsion injection method, and blood preparation.
      It is most important to consider effective nutritional management methods that do
      not require the insertion of a central venous catheter.

PMID- 15565902
TI  - [Appropriate antibiotic prophylaxis and treatment in surgery--comparison of
      concepts in North America and Japan].
AB  - Three principles must be followed to maximize the benefits of antimicrobial
      prophylaxis (AMP): 1) use an AMP agent that is bactericidal with a spectrum that
      covers the most probable intraoperative contaminants; 2) the initial dose of AMP
      agents should be given no more than 30 min before the skin is incised: and 3)
      maintain effective levels of antibiotics throughout the surgery and until at most
      a few hours after the incision is closed in the operating room. These
      recommendations have become standardized in North America and Europe. A few
      controversies, however, persist in Japan, especially concerning the duration of
      AMP. Most practitioners recommend that prophylaxis be continued until
      postoperative day 3 to 4. However, some authors reported that the administration
      of AMP agents for 3 to 4 days causes the development of resistant strains. It is
      thus necessary to formulate national guidelines for appropriate AMP which are
      validated by the results of randomized, controlled trials conducted in Japan. In
      the treatment of postoperative infections, Gram-stain-based antibiotic selection
      is necessary and full knowledge of the interrelationships between
      pharmacokinetics and pharmacodynamics is important for determining effective
      regimens. The time that serum levels exceed the minimum inhibitory concentration
      is the most significant parameter determining the efficacy of beta-lactams,
      whereas the log area under the curve and peak serum level are the major
      parameters for aminoglycosides and new quinolones, respectively. Careful
      application of these concepts should allow surgeons to use more optimal dosing
      regimens in Japan.

PMID- 15565903
TI  - [Preventive strategies for nosocomial pneumonia].
AB  - This article reviews the epidemiology, risk factors, pathogenesis, diagnosis,
      treatment, and prophylaxis of ventilator-associated pneumonia (VAP), which is one
      of the most important infectious complications during the perioperative period.
      The definition of VAP is a nosocomial pneumonia occurring more than 48 h after
      endotracheal intubation and initiation of mechanical ventilation. Early
      liberation from the ventilator and the use of non-invasive positive-pressure
      ventilation are useful in preventing VAP. The early institution of appropriate
      antimicrobial therapy contributes to a good outcome. The initial therapy to
      ensure adequate coverage of potentially infective organisms should be accompanied
      by deescalation, or discontinuation, when the microbiological data became
      available. Useful preventative strategies include subglottic suctioning of pooled
      secretions just above the endotracheal tube cuff and oral care because of the
      pathogenesis of VAP.

PMID- 15565904
TI  - [Surgical site infection surveillance].
AB  - Surgical site infections (SSI) are major complications after surgical procedures,
      since they prolong the hospital stay, increase treatment costs and diminish
      patient satisfaction markedly. In the United States SSI surveillance is carried
      out in the framework of the NNIS system; at present more than 300 medical
      institutions are participating. In comparison with Europe and the United States
      SSI surveillance had a late start in Japan. The Japanese Society of Environmental
      Infections established the Japanese Nosocomial Infection Surveillance System in
      1998 and initiated SSI surveillance in the same year. Up to October 2003, in
      total 20,948 cases from 36 institutions have been registered. SSIs occurred in
      1,394 cases, this corresponds to an incidence of 6.7%. When we look at the
      numbers of SSIs by the organs operated on, the incidence figures in the field of
      gastrointestinal surgery were by far the highest ones. Since July 2002, 50
      institutions all over Japan are participating in SSI surveillance that has
      developed into a national scheme under the auspices of the Japanese Ministry of
      Health and Welfare. The activities supervised by the Ministry will for some time
      be limited to these 50 institutions. Aiming at a further spread and quality
      enhancement of SSI surveillance in Japan in October 2002 the SSI Surveillance
      Study Meeting was founded. It is anticipated that through the activities of this
      organisation a large number of institutions will participate in SSI surveillance,
      that reliable surveillance data will established and that SSIs will decrease in
      Japan.

PMID- 15565905
TI  - [Use of the Zeus robotic surgical system for cardiac surgery].
AB  - The development of closed chest cardiopulmonary bypass systems has opened the
      door for totally endoscopic cardiac surgery. We used the robotic surgical system
      ZEUS for closure of the atrial septal defect (ASD) in three patients. Under one
      lung ventilation, Port-Access cardiopulmonary bypass system of the drainage from
      the right internal jugular vein and the the right femoral vein and the return to
      the right femoral artery was started after port placement at the forth
      intercostal space of the right thoracic wall. ASD direct closure was achieved by
      using robotic surgical system ZEUS under cardiac arrest. The three patients were
      discharged in 7 days after the operation uneventfully. The robotic surgical
      system ZEUS can make cardiac surgeries less invasive than ever.

PMID- 15565906
TI  - [What we can learn from a case of medical malpractice].

PMID- 15565907
TI  - Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.
AB  - The current document bestows an expert synopsis of key new information presented
      at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy
      (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and
      policies on antimicrobial prescribing, novel mechanisms of resistance in
      Streptococcus pneumoniae, and current epidemiological trends in global
      resistance. Novel information on new (and existing) antimicrobial agents--new
      penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides,
      glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin,
      aminomethylcyclines, glycylcyclines, and newer formulations of agents such as
      amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be
      controlled through use of more potent agents. Improved strategies for the use of
      existing antimicrobial agents, such as the use of high-dose regimens, short
      course therapy, also may delay or reduce the development of resistance and
      preserve the value of our antibiotic armamentarium.

PMID- 15565908
TI  - Antimicrobial susceptibility patterns in Pseudomonas aeruginosa: data from a
      multicenter Intensive Care Unit Surveillance Study (ISS) in the United States.
AB  - The objectives of this study were to analyze susceptibility rates and patterns in
      Pseudomonas aeruginosa isolates from patients in intensive care units (ICU). A
      total of 2209 isolates in 1995/1996 and 2672 in 2001/2002 were tested at United
      States sites participating in the ICU Surveillance Study. In both periods, of the
      agents tested, amikacin was the most active and ciprofloxacin, the least.
      Resistance to common antipseudomonal agents tested increased from 1995/1996 to
      2001/2002; the rise was least for amikacin (2%) and greatest for ciprofloxacin
      (16%). The proportion of isolates susceptible to all six antipseudomonal agents
      tested since 1996 decreased from 60.4% to 48.9% in 2001/2002. Examination of MIC
      distributions for the two periods showed that for some drugs, e.g. imipenem and
      ceftazidime, the populations of susceptible and resistant isolates remained
      distinct, although the resistant population increased. For other drugs, e.g.
      amikacin and piperacillin-tazobactam, the MIC distribution shifted upward over
      time. The categorical agreement between agents of the same or like classes for
      isolates tested in 2001/2002 was highest for ciprofloxacin and levofloxacin
      (93.2%, with 1.2% major errors) and lowest for the aminoglycosides (81.3%, with
      10.2% major errors). We can conclude that resistance to antipseudomonal agents
      among ICU isolates of P. aeruginosa, especially fluoroquinolones, is increasing.
      The resistance rate for some antipseudomonal agents may not accurately reflect
      shifts in the MIC distribution curve.

PMID- 15565909
TI  - RpoB gene mutations in rifampin-resistant Mycobacterium tuberculosis strains
      isolated in the Aegean region of Turkey.
AB  - Although DNA sequencing method has not been used routinely for detecting
      resistance of Mycobacterium tuberculosis to antituberculosis drugs, it is
      suggested for the investigation of gene mutations causing resistance. Using DNA
      sequencing (Automated Applied Biosystems), we attempted to determine mutations in
      the 81-bp cor region (rifampin resistance determining region) of the rpoB gene in
      48 Mycobacterium tuberculosis strains found to be rifampin resistant by classical
      phenotypic methods. Of the 48 strains, 46 (95.8%) were found to have rpo gene
      mutations with 13 different types while in two (4.2%) of the 48 strains, no
      mutations were detected. None of the strains had mutations at more than one
      codon. Point mutations at the 531st (52.1%) and 526th (18.9%) codons were
      frequent. The most frequent point mutation was Ser531Leu, and it was found in 21
      (43,8 %) of 48 strains. This is the first study from Turkey, reporting Ser522Leu
      point mutation in one isolate and deletion of 515th codon (ATG - Met) in two
      isolates.

PMID- 15565910
TI  - Polyurethanes loaded with antibiotics: influence of polymer-antibiotic
      interactions on in vitro activity against Staphylococcus epidermidis.
AB  - Acidic or basic polyurethanes were loaded with antibiotics to develop materials
      to prevent medical device-related infections. A correlation between polymer
      antibiotic interactions and amount of drug absorbed by polymers and released over
      time was found. Since the employed antibiotics, i.e. amoxicillin, cefamandole
      nafate, rifampin and vancomycin, possessed at least an acidic group in their
      structural formula, the introduction of basic tertiary amines in the polyurethane
      side-chain resulted in an increased polymer ability to adsorb antibiotics.
      However, a stronger ionic interaction between this polymer and the antibiotics
      caused a release of lower amount of drug over time. Antibiotics released from
      polymers inhibited Staphylococcus epidermidis growth on agar. Antibiotic-loaded
      polyurethanes kept in water for increasing times were still able to show
      inhibition zones of bacterial growth. The antibacterial activity lasted up to 3
      hours for amoxicillin, 24 hours for vancomycin, 8 days for cefamandole nafate and
      8 months for rifampin.

PMID- 15565911
TI  - Oxacillin- and mupirocin-resistant Staphylococcus aureus: in vitro activity of
      silver sulphadiazine and cerium nitrate in hospital strains.
AB  - Nasal carriage is an important reservoir of oxacillin-resistant Staphylococcus
      aureus (ORSA). Mupirocin is a topical drug used to remove S. aureus from nares.
      However, isolates resistant to mupirocin have been reported all over the world.
      Silver sulphadiazine (SSD) is a topical agent, which when associated with cerium
      nitrate (CN), has been shown to be useful in the treatment of burn infections and
      could be an alternative drug for patient decolonization. Susceptibility to
      oxacillin in 203 S. aureus isolates was evaluated by the agar diffusion test,
      while the agar diffusion and agar dilution methods were used for mupirocin. A PCR
      multiplex method was performed to detect the mecA and ileS-2 genes. Minimum
      inhibitory concentration (MICs) to SSD and CN, used alone or in association, were
      determined by the agar dilution method. One hundred and sixty-three (80.3%)
      strains were oxacillin-resistant, and 37 (18.2%) were mupirocin resistant. The
      MIC of SSD alone or in association with CN was 64 microg/mL, while for CN alone
      was 2048 microg/mL for all isolates. SSD presented anti-staphylococcal activity
      at concentrations (64 microg/mL) much lower than those commonly used in
      commercial preparations (10 mg/g) and had good activity against mupirocin
      resistant strains, showing that this drug could be used for nasal decolonization
      in ORSA carries.

PMID- 15565912
TI  - Comparative in vitro cytotoxic effects of ornidazole, metronidazole and
      ciprofloxacin against Trichomonas vaginalis trophozoites.
AB  - A strain of Trichomonas vaginalis, isolated from a patient complaining of vaginal
      discharge, was incubated and cultivated to compare the in vitro effects of
      ornidazole, metronidazole and ciprofloxacin on T. vaginalis trophozoites in terms
      of minimal inhibition concentrations (MICs) and minimal lethal concentrations
      (MLCs). MIC levels at 24 hours for ornidazole, metronidazole and ciprofloxacin
      were 50 mg/mL, 50 mg/mL, and 750 mg/mL. Corresponding MLC levels were the same.
      In this in vitro study, ornidazole was found to be the most effective drug among
      3 drugs tested against T. vaginalis trophozoites in terms of MIC and MLC levels.
      It is interesting to note that ciprofloxacin, although not as effective as the
      others, also had some cytotoxic effect on T. vaginalis trophozoites.

PMID- 15565913
TI  - Microbiological evaluation of commercial probiotic products available in Italy.
AB  - Scientific evidence of the prevention and therapy of some intestinal diseases is
      accumulating in regard to probiotic products. However, sufficient information on
      the use of probiotics in specific therapies is not yet available and, above all,
      there is no clear legislation about these products in Europe. In this study, we
      evaluated five different probiotic products commercially available in Italy for
      their qualitative and quantitative microbial content after about 12 and 22 months
      of storage. We also evaluated the stability of lactobacilli to 0.3% bile salts
      and to pH of 3.58 and 7.98. There were discrepancies between the declared content
      and our results found after storage for 4 of the tested products. Bile salts and
      basic pH did not affect the growth of the lactobacilli tested, while for 2 tested
      products 6 hours at acid pH produced a complete inhibition of bacterial growth.
      Our results suggest the need for clear legislation and adequate control of the
      manufacturing of probiotic products.

PMID- 15565914
TI  - Antifungal activity of amphotericin B and itraconazole against filamentous fungi:
      comparison of the Sensititre Yeast One and NCCLS M38--a reference methods.
AB  - The susceptibilities of 81 clinical isolates of Aspergillus spp., Fusarium spp.,
      and Scedosporium spp., to amphotericin B and itraconazole were determined by the
      colorimetric microdilution method Sensititre and the reference microdilution
      method of NCCLS standard M38-A for filamentous fungi. No major discrepancies were
      found and agreement ranged between 86.4% to 84% and 69.1% to 86.4% for
      amphotericin B and itraconazole respectively at 48 h and 72 h of incubation by
      using the recommended endpoints. Within two two-fold dilutions, high levels of
      agreement were found in general for amphotericin B at 48 or 72 h (86.4 to 87.7%)
      and itraconazole (91.4 to 93.8%). Relatively better agreement was found for
      itraconazole at 72 h of incubation and 48 for amphotericin B.

PMID- 15565915
TI  - In vitro testing of Aspergillus fumigatus clinical isolates for susceptibility to
      voriconazole, amphotericin B and itraconazole: comparison of sensititre versus
      NCCLS M38-A using two different inocula.
AB  - Voriconazole, amphotericin B and itraconazole were tested in vitro against 18
      strains of Aspergillus fumigatus isolated from cystic fibrosis patients.
      Susceptibility was tested with the broth microdilution method (M38-A protocol
      NCCLS). Results of this reference method were compared with those of an
      experimental commercial microdilution broth method (Sensititre). Two different
      inocula, prepared from 2- and 7-day cultures, were used. Minimum inhibitory
      concentrations (MICs) of the reference method ranged from 0.25 to 2 microg/ml for
      voriconazole, 0.06 to 1 microg/ml for amphotericin B, 0.016 to >16 microg/ml for
      itraconazole. There were no significant differences in the MIC ranges or MIC90
      values obtained with the two testing methods or with the two types of inocula.
      These findings confirm the good in vitro activity of voriconazole, itraconazole
      and amphotericin B against A. fumigatus. They also indicate that reliable
      susceptibility data can be generated more rapidly by commercial systems and use
      of 2-day cultures for inoculum preparation.

PMID- 15565916
TI  - Preclinical studies on detection of circulating melanoma cells in patients:
      telomerase as a recognition marker of malignancy.
AB  - Preclinical studies based on a "simulation design", were performed with cultured
      melanoma cells prelabeled with 51Cr, added to normal blood and subjected to
      separation and recognition steps. Mononuclear cells (MNC) were isolated on
      ficollhypaque gradient, and melanoma cells were separated from lymphocytes using
      anti-CD45 immunomagnetic beads. Malignant cells were then recognized by measuring
      telomerase activity (TRAP and TRAP-ELISA assays). It was found that: (a)recovery
      of prelabeled cells present in MNC did not exceed 75%; (b) further recovery of
      prelabeled cells after separation from lymphocytes did not exceed 68%. Therefore,
      the overall recovery of prelabeled cells did not exceed 48%; (c) the entire
      procedure was able to reliably detect as few as 30 malignant cells added to
      normal blood, providing a telomerase signal significantly higher than that found
      in absence of melanoma cells. These results furnish the technical bases for
      developing a tumor detection assay in the blood of melanoma patients.

PMID- 15565917
TI  - Irinotecan combined with bolus 5-fluorouracil and folinic acid for metastatic
      colorectal cancer: is this really a dangerous treatment?
AB  - Rothenberg et al called for caution in the palliative use of irinotecan, 5
      fluorouracil (5-FU) bolus and leucovorin (IFL schedule), because of early
      treatment related deaths in C89803 and N9741 studies. The objective of our
      multicenter phase II study was to evaluate the efficacy and safety of the
      combination of 5-FU bolus, folinic acid (FA) and irinotecan as first-line
      chemotherapy for metastatic colorectal cancer. From December 1999 to June 2002
      138 patients (pts) were treated. The chemotherapy regimen was as follows:
      irinotecan 125 mg/m2 i.v. over 90 min and 5-FU 500 mg/m2 preceded by FA 20 mg/m2,
      both given by bolus, weekly, for 4 weeks every 6 weeks. Treatment continued until
      disease progression or unacceptable toxicity. Total number of administered cycles
      was 404. Average dose intensity was 75%. 47 out of 131 evaluable pts achieved a
      complete (n = 6) or partial (n = 41) response, leading to an overall response
      rate (RR) of 36% [95% confidence interval (CI) 24% to 48%], stable disease was
      registered in 50 (38%). The estimated median time to progression and survival
      were 6.5 months (95% CI 5.2-9.4) and 16.6 months (95% CI 15.1-19.3) respectively.
      Two-year survival was 35%. Toxicity was well manageable. In 18 (13.8%) pts the
      chemotherapy was stopped because of toxicity. Treatment related death was not
      observed. Close clinical monitoring, early recognition of toxicity, immediate
      therapeutic intervention are recommended for pts receiving IFL. In our experience
      this regimen has manageable toxicity and appropriate level of dose intensity and
      seems to be a good option for first-line therapy in metastatic colorectal cancer.

PMID- 15565918
TI  - New proposal for the treatment of nodular basal cell carcinoma with intralesional
      5-aminolevulinic acid.
AB  - Photodynamic therapy (PDT) is a treatment modality using a photosensitizer, light
      and oxygen to cause photochemically-induced selective cell death. Topical PDT is
      most suitable for thin lesions such as superficial basal cell carcinoma and
      actinic keratoses in dermatology. Results with PDT as treatment of thicker
      lesions such as nodular basal cell carcinoma appear to have a limited role
      because the photosensitizer or the light cannot penetrate deeply enough into the
      thicker tumor volume. In this preliminary study we use intralesional
      administration of 5-aminolevulinic acid to enhance the efficacy of the
      photosensitivity of nodular basal cell carcinomas, thus improving clinical cure.

PMID- 15565919
TI  - Multiresistant Stenotrophomonas maltophilia tunneled CVC-related sepsis, treated
      with systemic and lock therapy.
AB  - In the last decade, a remarkable increase in the incidence of nosocomial Gram
      negative infections has been observed. These pathogens represent a substantial
      problem in clinical practice, due to the high resistance profile of most commonly
      used antibiotics. This phenomenon is surely a co-factor that exposes these
      susceptible patients to infections caused by selected pathogens like
      multiresistant Gram-negative rods. A typical example is represented by VAP
      (ventilator-associated pneumonia) sustained by Acinetobacter spp., Pseudomonas
      aeruginosa, Bulkolderia cepacia. The Authors describe a case of a central venous
      cather (CVC)-related Stenotrophomonas maltophilia sepsis in a patient affected by
      solid tumor, successfully treated with systemic antibiotic therapy associated
      with "lock therapy". This combination was able to cure the infection, allowing
      the patient to continue chemotherapy and saving the in situ CVC. The surveillance
      of CVCs, good adherence to the protocols and guidelines and "good practice" are
      the cornerstones for the prevention of nosocomial infections.

PMID- 15565920
TI  - Capnocytophaga spp. brain abscess in an immunocompetent host: problems in
      antimicrobial chemotherapy and literature review.
AB  - The fourth case report of a brain abscess due to the fastidious Gram-negative
      organism Capnocytophaga spp. is described and discussed on the grounds of
      clinical, microbiological, and therapeutic evidence. A probable origin from a cat
      bite and/or an underlying severe mandibulary granuloma is suspected. Due to lack
      of clinical and neuroradiological response to neurosurgery and a combination of
      imipenem-amikacin-clindamycin-fluconazole, second-line empiric llnezolid
      treatment proved rapidly successful, in the absence of further microbial
      isolations. In vitro antimicrobial susceptibility testing is often unpredictable
      for Capnocytophaga spp., and agents usually active on Gram-positive organisms may
      also be effective, both in vitro and in vivo. Due to its favorable brain
      penetration and its dual mode of administration, linezolid may be an alternative
      option for patients with multiple risk factors, brain abscess of suspected
      polymicrobial origin, and lack of response to empiric or culture-driven
      therapeutic attempts.

PMID- 15565921
TI  - In vitro activity of thiamphenicol, erythromycin and fluoroquinolones against
      Legionella pneumophila.

PMID- 15565922
TI  - Analysis of antimicrobial susceptibility and virulence factors in Helicobacter
      pylori clinical isolates.

PMID- 15565923
TI  - Oro-facial soft tissue injuries in Nigerian children: a five-year review.
AB  - A review of 64 soft tissue maxillofacial injuries in 50 children seen and managed
      at the University College Hospital, Ibadan over a five-year period was made. The
      age range was from 3months to 15years. The highest occurrence was in the 0-5
      years old children (60%). The predominant type of soft tissue injuries was
      lacerations (75.0%). Falls (66.0%) were the most common aetiology followed by
      road traffic accidents (18.0%). There was a higher involvement of males, than
      females (M: F of 2.3:1). The tongue (31.3%) was the most commonly affected site
      of soft injury followed by the lips (29.7%) and cheeks (10.9%). Slightly less
      than half (46%) of the patients presented within 24 hours of injury. Direct
      suturing was done in 24% of the children while debridement and conservative
      management was carried out in 76%.

PMID- 15565924
TI  - A review of hypertensive disorders of pregnancy.
AB  - The detection and clinical management of hypertension in pregnant women are
      complicated by the concern for fetal development and survival as well as for the
      health of the mother. Preeclampsia describes a common syndrome that occurs in the
      second half of pregnancy and often manifesting with hypertension and proteinuria.
      It occurs in up to 10% of all pregnancies. The factors that initiate preeclampsia
      are unknown and still a subject of intense clinical research by both
      Obstetricians and Physicians. The blue print for the development of preeclampsia
      is probably laid down early in pregnancy, and delivery of the fetus and placenta
      remains the only effective treatment. Severaclinical, biophysical and biochemical
      tests have been reported in the world literature to predict the development of
      preeclampsia. Also, numerous reports have described the predictive value of every
      possible substance that can be measured in maternal blood or urine. However, the
      presence of microalbuminuria is an important clinical finding in pregnant women.
      Indeed, urinary albumin excretion when used as a single test has shown that
      albumin excretion was higher at booking in those that later developed
      hypertensive disorders of pregnancy than those that did not have the condition.
      It had a higher sensitivity and poor predictive value. In conclusion, the factors
      that are responsible for hypertensive disorders of pregnancy remain unknown and
      treatment is still difficult. The search for an ideal predictive test or tests
      should therefore be a continuous exercise.

PMID- 15565925
TI  - Experience with intravaginal misoprostol in the management of intra-uterine fetal
      death.
AB  - This collaborative study between the departments of Obstetrics and Gynaecology of
      the University College Hospital, Ibadan and Federal Medical Centre, Abeokuta
      assessed the value of intravaginal misoprostol in the management of intra-uterine
      fetal death. Fifty-six women at gestational ages between 17 weeks and term
      admitted for intra-uterine death with no contraindications to misoprostol
      received 400mcg of misoprostol administered intravaginally 12-hourly, until the
      establishment of effective uterine contractions. The mean gestational age was
      27.9 weeks+/-7.1(SD) and the mean Bishop score was 2.7+/-2.4(SD). The mean
      duration of onset of contractions was 5.0 hours+/-8.4 (SD); the mean induction
      delivery interval was 17.5 hours+/-6.3(SD). Ninety three percent of the women had
      expelled within 48 hours. Successful induction was achieved in all women.
      Prophylactic vacuum aspiration was performed (lower gestation only) in 19.6% of
      cases. Fever, nausea and vomiting were the commonest side effects (7.1%). Neither
      gestational age nor the cervical score significantly affected the insertion
      contraction or induction-delivery intervals. Intra-vaginal Misoprostol at the
      dosage administered is safe, effective and reduces staff workload.

PMID- 15565926
TI  - Health related practices of students of the University of Ibadan.
AB  - University students are predisposed by environmental factors to adoption of
      habits that impact on their health Smoking, alcohol abuse, a sedentary lifestyle
      and failure to use health services appropriately may all impair current or future
      health. These students represent a large population of young persons but have not
      been recognised as a specific concern among health care planners except in the
      area of reproductive health and sexuality. Seven hundred and fifty students of
      the University of Ibadan were randomly selected from the halls of residence by
      multi stage sampling. Verbal consent was obtained and trained student peers
      administered questionnaires to the subjects Seven hundred and twenty-four
      students returned completed questionnaires, an overall response rate of 96.5% The
      respondents consisted of 484 males and 240 females Six hundred and two were
      undergraduate and 122 were graduate students. All the university's faculties were
      represented. Most (92.3%) of the respondents were single The mean age of the
      group was 23.8 years (SD 4.6). Current and ever used smoking prevalence was 5.7%
      and 23.2% respectively. Smokers were predominantly males pursuing degrees in the
      Arts and Humanities. Current and ever use of alcohol were reported by 24.7% and
      46.1% respectively of the students. Main associations with alcohol consumption
      were with male gender, age less than 30 years, single marital status and non
      medical course of study. Only 12 students (1.8%) exercise daily. This study
      demonstrates the need for continued surveillance of health related habits of
      young persons, not only for the benefit of the individual students but also for
      the general population for whom these educated persons represent lifestyle
      models.

PMID- 15565927
TI  - Efficacy of herbal remedies used by herbalists in Oyo State Nigeria for treatment
      of Plasmodium falciparum infections--a survey and an observation.
AB  - In the course of evaluating the contribution of phytomedicine to possible drug
      discovery of antimalarial drugs, an ethnomedical survey of specialized children
      traditional clinics was done. In the observational multi center study, efficacy
      of eight different herbal remedies, each consisting of 3-8 ingredients and
      administered by herbalists were investigated in clients enrolled in the six
      traditional clinics in Oyo (urban center) and Otu (rural center) of Oyo State,
      Nigeria. The clients, aged between six months and fifteen years with clinical
      symptoms of malaria were enrolled in the clinics of the herbalists, as their
      usual practice. Oral informed consents were obtained from their parents or
      guardians. Microscopic diagnosis of malaria infection was used to evaluate
      parasitaemia and validate efficacy of herbal remedies. Results of the analysis
      showed that, of the 163 clients of the herbalists, only 62 (30 from Oyo, 32 from
      Otu) had microscopically confirmed P. falciparum infection. Only results from 54
      clients (29/30 (Oyo) and 25/32 (Otu) with P. falciparum infection could be
      evaluated. Plasmodium falciparum infection in 88% (23/29) of clients from Oyo
      responded to treatment with the herbal remedies while cure rate in clients from
      Otu was 42% (13/25). Parasite densities ranged from 171 to 53,613
      parasites/microl blood and 87 to 36,209 parasites/microl blood in patients from
      Oyo and Otu respectively. The herbalists administered the remedies and Gossypium
      arboreum, Anarcadium occidentalis, Citrus medica, Phyllanthus amarus and Lippia
      multiflora were the main ingredients in the efficacious remedies. The herbalists
      gave detailed descriptions of each of the 8 herbal remedies proffered. The
      results confirm the efficacy of two of the eight herbal remedies, thereby
      validating the role of ethnomedicine as a possible source for the discovery of
      new chemotherapeutic agents in the treatment of P. falciparum malaria.

PMID- 15565928
TI  - Prevalence of coronary heart disease risk factors in Nigerians with systemic
      hypertension.
AB  - This study is to determine the prevalence of coronary heart disease risk factors
      in Nigerians with systemic hypertension. Serum lipid profile and fasting blood
      glucose were determined in one hundred and thirty six newly diagnosed
      hypertensives selected from the Medical Outpatient Department. Basic demographic
      data as well as medico-social history was extracted from the records. Coronary
      heart disease risk was calculated from the ratios of high-density lipoprotein
      cholesterol to total cholesterol. High risk were defined as CHD ratio <0.18,
      while average and low CHD risk ratio was 0.18 to 0.40 and >0.40 respectively,
      according to the European Athersclerosis society guidelines. There were 76
      (55.9%) males and 60 (44.1 %) females aged 24-70 years (mean = 47+8.5) studied.
      The coronary risk ratio in the study groupts was 0.34 as against 0.57 in the
      controls. The prevalence of high coronary heart disease risk in newly diagnosed
      hypertensives was 22%. The overall prevalence rate of hypercholesterolaemia was
      62.5%, with high-risk group prevalence of 70%. The high-risk group was also
      associated with other non-lipid factors such as overweight -54% (BMI > 25Kg/m2),
      glucose intolerance-55% (FBS > 6.1 mmol/L), and alcoholism (55%). The overall
      prevalence of hypertriglyceridaemia was 20.4%, with higher serum values amongst
      females, and no risk group difference. The female patients were more affected by
      the metabolic risk parameters especially in the high and average risk groups.
      There is a need therefore, for clinicians to be encouraged to investigate lipid,
      lipoprotein cholesterol indices and other non-lipid risk factors to calculate the
      risk run by hypertensive patients of developing cardiovascular complications.

PMID- 15565929
TI  - Comparative study of oral hygiene status of HbSS subjects and controls.
AB  - There is paucity of information on the oral health status of individuals with the
      HbSS gene in Nigeria. This study was carried out to determine the state of their
      oral hygiene, compare this with unaffected people and create awareness of
      importance of oral health care in the patients and their parents. Three hundred
      and thirty-six subjects, aged 1-45 years and comprising 185 HbSS and 151 controls
      took part in this study. They were seen in three hospitals in Lagos-General
      Hospital Lagos, Massey Street Children Hospital and Lagos University Teaching
      Hospital. They were examined using the Simplified Oral Hygiene Index, (OHIS).
      Mean OHI-S scores for HbSS subjects and controls were 1.24+/-0.95 and 0.66+/-0.58
      respectively (P< 05). There was no significant difference in OHI-S score across
      the socio-economic classes of both groups (P> 05). Females in both groups had
      cleaner mouths than males. It is concluded that the controls had cleaner mouths
      than those with HbSS. Socio-economic class did not influence their oral hygiene.
      It is recommended that preventive oral health care should be included in the
      management of HbSS patients.

PMID- 15565930
TI  - Effects of different brands of fluoride dentifrices on dental caries incidence in
      the rat.
AB  - The effectiveness of 3 different brands of fluoride-containing dentifrices on the
      prevention of dental caries was investigated in molars of young rats. Forty
      albino Wistar rats weighing 50-80g, 28 males and 12 females were inoculated in
      the mouth with streptococcus viridans daily from day 1 to day 5 of the
      experiment. The animals were then divided into four groups and fed with rat
      pellets containing 60% sucrose added as granulated sugar. All the groups were
      given water ad libitum. Group I had daily tooth brushing with water and served as
      the control while groups II, III and IV received daily brushing of their molar
      teeth with different fluoride--containing dentifrices: (Maxam, Florish and Close
      Up respectively. All topical treatments were given for one minute daily per rat
      from day 6 to day 56 of the experiment. At the end of the experiment the animals
      were sacrificed, the jaws removed and the teeth were scored for occlusal caries.
      All fluoride--containing dentifrices tested reduced caries in the following
      order: Maxam 37.86%, Florish 59.22% and Close-Up 57.28%. This study confirmed
      that fluoride incorporated in Florish and Close-Up showed significant levels of
      caries reduction (P <0.01) and (P <0.05) respectively in the rat. It also adds
      credence to Dental Health Education in the application of various tooth pastes in
      oral hygiene measures.

PMID- 15565931
TI  - Reducing maternal mortality from ruptured uterus--the Sokoto initiative.
AB  - Uterine rupture is the most common cause of maternal mortality in our
      institution. Case fatality for the year 2001 was 47%. Health care including
      emergency obstetric care (EmOC) is not free, hence, delays in receiving care
      could occur in patients with limited resources. The objectives of the study were
      to promote access to emergency obstetric care through a loan scheme for indigent
      patients with ruptured uterus and determine the success or otherwise of the
      scheme. The scheme was initiated in January 2002, with the sum of thirty eight
      Thousand Naira (about 300 US dollars) by consultant obstetricians in the
      department. Funds were released to the patient only after assessment of her
      financial capability to enable her get emergency surgical packs. All that was
      required was a promise to pay back the loan before discharge. Following
      resuscitation, surgery was performed by one of the consultants. Eighteen cases of
      ruptured uterus have been managed. Treatment was initiated within 30 minutes of
      admission. Admission-laparotomy interval averaged 3.5 hours (+/-1.2). There were
      two maternal deaths, giving a case fatality of 11% (2/ 18). The case fatality
      from a previous study from the same centre was 38% (16/42). There was a
      significant difference in case fatality between the two studies (P<0.05;
      confidence limits are-0.328 and -0.211). Of the seventeen patients that benefited
      from the scheme, 16 repaid the loan before discharge (94% loan recovery). Only
      one patient defaulted with five thousand Naira (40 US dollars). A loan scheme for
      indigent patients with ruptured uterus that enabled them receive emergency
      obstetric care reduced case fatality. Loan recovery was good. In our quest to
      reduce maternal mortality in low-income countries without health insurance
      policies, there might be a need to extend similar initiative to other obstetric
      emergencies.

PMID- 15565932
TI  - Reproductive health knowledge and use of contraceptives among adolescent mothers
      in a sub-urban community in Oyo State, Nigeria.
AB  - This survey explored the reproductive health knowledge and use of contraceptives
      among 316 young mothers in Ogbere, a sub-urban community in Oyo State, Nigeria. A
      cluster sampling technique was used to recruit the respondents and data were
      collected from them through face-to-face interviews using questionnaires. The
      ages of the respondents ranged from 17-20 with a mean of 18.9. The majority
      (76.9%) of the respondents were married and had primary school education (72.8%).
      Fivepercent had lost a pregnancy due to abortion, miscarriage or still birth.
      Forty-three percent had fair, 34.5% poor, and 22.5% good knowledge of
      contraceptives; 53% did not know any of the routes for HIV transmission. A large
      majority (70%) had never used any contraceptives, 29% had done so. Eighty percent
      of those who had ever used any contraceptive were using one at the time of the
      survey. The most popular contraceptives used were condoms (44.4%) and pills
      (16.1%). Interventions to improve the economic status and promote use of
      contraceptives are recommended for this population.

PMID- 15565933
TI  - A study of determinants of low birth weight in Abha, Saudi Arabia.
AB  - This study examined the role of women's work as a possible determinant (among
      others) of low birth weight in the population of women followed in a Primary
      Health Care (PHC) center in Abha, Southern Saudi Arabia. All antenatal care files
      for all deliveries in the preceding 5 years were studied and the relevant data
      from 7067 files were collected and analyzed. Low birth weight was significantly
      higher in working mothers (odds ratio=1.31), adolescent mothers (odds ratio=
      2.56), and low parity mothers (OR= 1.28). Anemia of the mother contributed an
      odds ratio of 1.23 for low birth weight baby and inadequate antenatal care (less
      than 3 visits during pregnancy) had an odds ratio of 1.9. Female babies were
      significantly more prone to low birth weight (odds ratio 1.34). It is suggested
      that further evaluation of women's work conditions to detect and remedy stressful
      conditions especially during pregnancies, health education and better antenatal
      care may prevent a good proportion of low birth weight deliveries.

PMID- 15565934
TI  - Assessment of doctors' management of severe malaria in urban centres in Eastern
      Nigeria.
AB  - Malaria remains a heavy burden in sub-saharan Africa and accounts for over one
      million deaths per annum. Prompt and appropriate management of severe cases is
      critical in both disease control and reduction in mortality. This study explores
      the management actions of doctors in urban settings in Nigeria. A survey of
      medical practitioners in four urban local government areas (LGAs) in two states
      in South- Eastern Nigeria was conducted. Using simple random sampling technique,
      sixty doctors were chosen in each of the four LGAs giving a total of two hundred
      and forty. They were interviewed on their management actions for children with
      severe malaria. The mean age of the doctors was 34.6 years. 83.5%(167) of them
      were males while 16.5% (33) were females. 65.5% (131) of the doctors attend to
      children regularly. The common features of severe malaria seen include; high
      fever 52.7% (69), persistent vomiting 27.5% (36), severe anaemia 24.4% (32),
      refusal of drinks 7.6% (10), convulsion 7.6% (10), loss of consciousness 4.6% (6)
      and respiratory distress 2.3% (3). 79.4% (104/131) of the doctors that see
      children regularly have diagnosed cerebral malaria in the last five years.
      Quinine is the drug of choice for the treatment of cerebral malaria 87.8% (115/
      131). 56.5% (74/131) of the practitioners see patients with severe anaemia
      requiring blood transfusion on a monthly basis. The monthly mean of such anaemic
      patient per physician is 6.7 patients. The median time for blood transfusion from
      time of request to onset of transfusion is 3 - 4 hours. The current state of
      health facilities and personnel is not meeting up with the malaria challenge.
      Urgent efforts need to be made to curb the scourge.

PMID- 15565935
TI  - A single blinded randomised trial to compare the efficacy and safety of once
      daily budesonide (400microg) administered by turbuhaler with beclomethasone
      dipropionate (400microg) given twice daily through a metered-dose inhaler in
      patients with mild to moderate asthma.
AB  - The study compared clinical efficacy and safety of beclomethasone dipropionate
      (BDP) given at a dose of 400microg in the mornings and evenings and delivered via
      pressurised metered dose inhaler (pMDI) with budesonide given via a dry-powder,
      inspiratory flow driven device at a daily dose of 400microg in the evening. The
      study was conducted as a week screening. 8-week open comparative clinical trial.
      At the commencement of the therapy, the baseline characteristics of the patients
      randomised into the two drug groups were comparable. Efficacy was assessed by
      changes in symptoms, number of times beta2-agonist was used and results of
      pulmonary function tests (PEF and FEV1) while safety was assessed by adverse
      event experiences. At the end of the study, 24 patients (12 in each group) were
      evaluated. Both drugs were effective in reducing asthma symptoms and frequency of
      beta2-agonist usage, as well as improving the lung function tests (FEV1 and PEF).
      However, budesonide given via Turbuhaler provided better effects in all
      parameters. The drugs were well tolerated and no adverse event was noticed in any
      of the patients. We therefore concluded that budesonide Turbuhaler administered
      once daily at a dose of 400microg is more efficacious than beclomethasone
      400microg twice daily administered via pressurized metered dose inhaler.

PMID- 15565936
TI  - Feasibility of thyroid ultrasonography in field studies in a developing country,
      Ghana.
AB  - This study was carried out to determine the feasibility of using ultrasonography
      for goitre estimation in the field situation. It is a cross sectional study that
      was conducted using community based cluster sample. Thyroid sonography was
      performed on 112 randomly selected school children aged 10 -15 years from two
      districts in the Greater Accra area of Ghana, using normative values for thyroid
      volume recommended by WHO/ICCIDD. The mean age of all subjects was 13.5 years+/
      0.13 SEM. The male to female ratio was 1:1. The mean height and weight of the
      children were 1.5 metres+/-0.9 SEM and 38.1 Kg+/-0.7 SEM, respectively. The mean
      body surface area was 1.27 m2+/-0.2. There were no significant gender differences
      in their ages (13.6yrs+/-0.2 SEM, 13.4yrs+/-0.1 SEM, respectively) and height
      (1.50m+/-1.6 SEM, 1.46m+/-1.7 SEM, respectively). The girls (40.0kg+/-1.2 SEM)
      weighed more than the boys (35.6kg+/-1.1). The mean and median urinary iodine
      concentration were 82.4+/-8.5 SEM and 67.9 ug/l, respectively. All the children
      examined had normal thyroid sonogram. The thyroid volumes ranged from 3.6 ml to
      15.3ml. The mean thyroid volume was 7.0ml+/-0.2 SEM and the thyroid volume was
      higher in the girls (7.5ml+/-0.3 SEM) than the boys (6.5ml+/-0.2 SEM). The
      criteria of thyroid volume per age and sex yielded a goitre prevalence of 1.8 %.
      In contrast, the criteria of thyroid volume by surface area yielded a goitre
      prevalence of 8 %. Our study has shown that it is feasible to employ
      ultrasonography for field studies to determine goitre prevalence in school
      children in a developing country such as Ghana. However, the best criteria for
      goitre in children in Ghana, requires to be confirmed in future studies.

PMID- 15565937
TI  - Characteristics of volunteers and non-volunteers for voluntary counseling and HIV
      testing among unmarried male undergraduates.
AB  - The 2001 HIV sero-prevalence survey in Nigeria revealed a rate of 5.8 percent
      with those under the age of 25 years having the highest prevalence rate. Most
      University students fall within this age group. This study is part of a larger
      study on the sexual behavior of youths and young adults and was designed to
      compare the characteristics of volunteers and non-volunteers for voluntary
      confidential counseling and HIV testing (VCT) among males. Six hundred and nine
      male undergraduate students were randomly selected and enrolled for the study.
      Data were collected using a pre-tested questionnaire. Of the 609, 51 (8.3%)
      volunteered to have their blood screened for HIV. All volunteers who received pre
      test counseling went for the HIV test. Volunteers were significantly older than
      the non-volunteers (P<0.0001), and were more likely to be sexually experienced
      (P=0.002). Among the sexually experienced, the volunteers were older at first
      sexual intercourse (FSI) (P<0.0001), and were more likely to have used a condom
      at FSI (P=0.001). Volunteers had significantly higher knowledge scores for
      HIV/AIDS (P=0.006), and the attitude to HIV/AIDS in both groups was positive. The
      marriage pattern of their parents with regard to polygyny was similar, and fewer
      volunteers had fathers in the higher socio-economic class and mothers who had
      completed secondary education (P<0.00001, (P=0.02). Among the 51 volunteers, 8
      (15.7%) tested positive. Those who tested positive were less likely to have lived
      with parents, and were all sexually experienced. Those who screened positive were
      also more likely to be currently sexually active and to have fathers with low
      level of education. Three (5.9%) of volunteers did not return for results and
      posttest counseling. One of the three was positive for HIV. Of those who tested
      positive, 3 (37.5%) reported not using the condom at all, while the rest were
      using it only occasionally. VCT among the youths is possible however, small
      numbers encountered in the study is a limitation and there is a need to replicate
      this study using larger numbers. Tertiary institutions should provide VCT
      services for the students where they can be counseled appropriately and
      continuously throughout their stay in the institution. This hopefully will reduce
      the number of new HIV cases seen.

PMID- 15565938
TI  - Ascorbic acid and mineral availability in two Nigerian plant foods.
AB  - This paper reports the effect of various concentrations of ascorbic acid on the
      availability of Fe, Zn, Ca and Mg in two popular plant foods--cowpea and
      amaranthus vegetable--in Nigeria. Ascorbic acid enhancement of iron availability
      was over 300 % and zinc by 200 % from 0-100 mg concentration. Availability of
      iron was further increased by 200 mg ascorbic acid in amaranthus but showed a 50
      % decrease in the legume. Availability of zinc was decreased by 200 mg ascorbic
      acid but to different levels in both plant foods. In the legume, maximum
      enhancement of Ca and Mg availability was exhibited at 100 mg ascorbic acid level
      but suppressed at higher concentrations. In amaranthus, maximum Ca enhancement
      was exerted by 200 mg ascorbic acid and 50 mg for Mg. Enhancement of Cu in the
      legume was marginally affected by ascorbic acid concentrations while inhibition
      of Cu was observed in amaranthus between 50-300 mg ascorbic acid concentrations.
      The effect of ascorbic acid on the availability of minerals seems to be
      concentration dependent and varies with theplant food.

PMID- 15565939
TI  - Carcinoma of the cervix co-existing with multiple pregnancy: a case report.
AB  - A case of a 38year old grandmultipara (Gravida9, Para7+1, all alive) woman with
      squamous cell carcinoma of the cervix co-existing with multiple pregnancy is
      presented. She had therapeutic termination of pregnancy with oxytocin at a
      gestation age of 18 weeks. This was followed by intracavitary and then
      extracavitary radiotherapy. The need to consider the possibility of carcinoma of
      cervix in bleeding disorders of early pregnancy and the importance of a thorough
      evaluation of such patients is emphasized.

PMID- 15565940
TI  - Socio-cultural factors affecting the spread of HIV/AIDS in Africa: a case study.
AB  - There is a disproportionate share of AIDS cases over the years in Africa. This
      has occurred in racial and ethnic minority populations, a finding likely related
      to social, economic and cultural factors. Certain socio-cultural and religious
      practices such as polygamy and giving a daughter away in marriage without
      considering the social life of the man are likely contributory factors to the
      higher prevalence of HIV/AIDS in women in this part of the world. This is
      illustrated with a case of Mr. M. S. who married two wives within four months
      interval, having lived a promiscuous life before marriage. One of the wives was a
      virgin at the time of marriage. Neither of wives had any symptoms suggestive of
      STD or HIV before marriage, however, the three of them tested positive to HIV-1
      following a visit to the special treatment clinic. He had genital herpes and his
      two wives also had vulvovaginal candidiasis, genital herpes and condyloma
      accuminata (genital warts). The husband would not want his HIV status declared to
      the wives. There is therefore a need to enact law on pre-marriage HIV screening
      for intending couples. Couple Pre-and post-test counseling must be encouraged and
      promoted. In addition, women should be empowered to negotiate safer sex.

PMID- 15565941
TI  - Public attitudes on the U.S. health care system: findings from the Health
      Confidence Survey.

PMID- 15565942
TI  - Development of a health-related quality of life questionnaire for Thai patients
      with rhinoconjunctivitis.
AB  - The objective of this study was to develop a disease-specific questionnaire for
      patients with rhinoconjunctivitis. All patients were recruited at the Out-Patient
      Clinic at Siriraj Hospital. Related topics were gathered from several sources,
      and a list of 63 items was produced. In phase I, the first version of the
      questionnaire was completed by 363 patients. Forty-eight items were identified by
      clinical impact analysis during the item removal process, two more questions were
      then added, giving a total of 50. Two hundred and forty-three patients completed
      the second version questionnaire in phase II. The average time taken to complete
      the questionnaire was 6.38 minutes. The item removal process in phase II was
      achieved by a multi-step process. There were 36 items in the third version
      questionnaire which consisted of six dimensions and two independent items as
      follows: symptoms (17 items), physical functioning (3 items), role limitations (3
      items), sleep (3 items), social functioning (3 items), emotions (5 items),
      general health (1 item), and absenteeism (1 item). The scores of each item ranged
      from 1 to 5; a lower score indicating a better quality of life. Data from the
      selected 36 items was extracted to test the validity and reliability of the final
      version. The floor and ceiling effects of the scores for each dimension were low.
      Multitrait multi-item analysis was conducted to examine construct validity. The
      scaling success of convergent and divergent validity was 100% and 94%,
      respectively. Internal consistency determined by Cronbach's alpha coefficient,
      was satisfactory (0.79-0.87). The study indicates that the questionnaire is
      suitable for use in clinical settings. While the test results are encouraging,
      further work needs to be done on the test-retest reliability and on
      responsiveness.

PMID- 15565943
TI  - Asthma knowledge among adult asthmatic outpatients in a tertiary care hospital.
AB  - We conducted a prospective, cross sectional survey on 94 asthmatic subjects using
      an interviewer-administered questionnaire to audit the level of knowledge of
      adult asthmatic outpatients at a tertiary care hospital, in order to determine
      the sources of asthma information and variables associated with poor asthma
      knowledge. Of the 94 subjects, 39.4% were ignorant of the inflammatory nature of
      asthma while 56.4% did not understand the role of prednisolone in acute
      exacerbation of asthma. Only 17.0% reported having a written action plan. Lower
      educational level and older age were significantly associated with lower asthma
      knowledge scores. The doctor was the main source of asthma information. Asthma
      knowledge scores were significantly higher among those who named the doctor,
      pamphlets, newspapers, internet and books as a source of asthma information. Our
      study demonstrates that many asthmatics have poor understanding of some aspects
      of their disease and have no written asthma action plan.

PMID- 15565944
TI  - Aeroallergen sensitivity among Thai children with allergic respiratory diseases:
      a hospital-based study.
AB  - One hundred and twenty patients, aged 3-15 years, attending the Allergy Clinic,
      Thammasat University Hospital, with allergic rhinitis, asthma or both conditions
      were studied. Standardized skin prick tests were performed with 15 common
      aeroallergens. The subjects were 85 boys and 35 girls with the mean age of 8.1
      years (SD = 3.4 years). There were 63 cases (53%), 22 cases (18%) and 35 cases
      (29%) diagnosed with allergic rhinitis only, asthma only and both conditions,
      respectively. The prevalence of asthma among the allergic rhinitis patients was
      36 percent whereas the prevalence of allergic rhinitis among the asthmatic
      patients was 61 percent. The sensitization patterns for major aeroallergens among
      the three groups were similar with the most common sensitized allergens as D.
      pteronyssinus, followed by D. farinae, American cockroach, Kopok and German
      cockroach, respectively. Among the atopic patients, a greater number of allergen
      reactivity was significantly associated with the increased risk of having their
      coexistence of allergic rhinitis and asthma (p = 0.0046; score test for trend of
      odds ratio).

PMID- 15565945
TI  - Skin sensitization to common allergens in Turkish wheezy children less than 3
      years of age.
AB  - Infants and small children with asthma are not commonly skin tested, as allergy
      is not considered to be a major cause of infantile asthma. The aim of this study
      was to determine the frequency of skin test positivity to various allergens in
      wheezy children less than 3 years of age. We evaluated 161 patients with
      infantile asthma (median age 20 months) and 100 healthy controls (median age 18
      months). Infantile asthma was defined as three or more episodes of wheezing in a
      child less than 3 years of age, whose symptoms improved on treatment with beta
      agonist and anti-inflammatory agents. All children were skin tested to house dust
      mites (HDM), pollens, molds, and cow milk extracts using prick technique. One
      hundred and eighteen (73.3%) children In the patient group tested positive to
      HDM, 84 (52.1%) to pollens, 37 (22.9%) to molds, and 16 (10%) to cow milk.
      Sensitization rates to HDM were significantly higher in the patient group than In
      the healthy controls. Sensitization rates to pollens were not statistically
      different between the two groups. There was no association between family history
      of atopy and frequency of sensitization to allergens in the wheezy and control
      groups. We concluded that skin sensitization to allergens was common In wheezy
      infants. The prevalence of sensitization to indoor allergens was higher than to
      outdoor or food allergens.

PMID- 15565946
TI  - Occupational asthma, eosinophil and skin prick tests and serum total IgE values
      of the workers in a plant manufacturing rose oil.
AB  - This study was aimed to determine the rate of occupational asthma (OA) in workers
      at a rose extracting plant. Specific clinical tests of 52 workers, randomly
      chosen from four local rose extracting plants, were statistically compared with
      the test results of 30 local control subjects of similar age and sex as the plant
      workers, but who had never worked in such a plant. There were no significant
      differences in pulmonary function tests (FVC, FEV1, FEV1/FVC, PEFR) between the
      control and test groups. Significantly higher serum total IgE values (p < 0.0001)
      were observed for the test subjects (239.08+/-240 IU/ml) compared to the control
      subjects (81.33+/-61.45 IU/ml). There were also significant differences (p <
      0.0001) in the number of eosinophils between the control and test groups, with
      corresponding mean values of 2.28+/-2.75% and 0.73+/-1.72%, respectively. A
      specifically prepared skin prick test using a rose allergen (Rosa domescena) was
      positive for 53.84% in the test subjects whereas only 5.33% positive test results
      were seen in the control group. We have demonstrated the involvement of Rosa
      domescena pollen in occupational allergy, through IgE-mediated hypersensitivity.
      It was concluded that the workers of a rose oil extracting plant are more
      susceptible to the rose pollens.

PMID- 15565947
TI  - The results of skin prick testing in patients with allergic rhinitis: a
      comparison between a multiple lancet device and a single lancet.
AB  - Skin prick testing (SPT) is widely used in the assessment of allergic disorders.
      Different SPT techniques are widely used. The aim of this study was to compare
      the response to SPT using a multiple lancet device (MLD) with the results of a
      single lancet (SL). Fifty patients with allergic rhinitis were included in this
      study. Initially, SPT was performed by a SL technique. After one week SPT was
      repeated using the MLD on all patients. The patients were tested with a panel
      containing 19 specific allergens including grass pollen, tree pollen, house dust
      mites, weed pollen allergen extracts, histamine and a negative control. The skin
      responses were recorded after 15 minutes for each device by measuring the
      diameter of the wheal and the erythema. The skin wheal responses for grass
      pollen, tree pollen, weed pollen and house dust mite allergen extracts obtained
      using the SL were generally significantly larger than those using the MLD. The
      comparison between the MLD and the SL methods revealed that SPT was positive with
      SL and negative with MLD in 176 tests (15.3%), and on the contrary SPT was
      positive with MLD and negative with SL in only 13 tests (1%). In conclusion, we
      claim that SPT using SL shows a higher degree of sensitivity and reproducibility.

PMID- 15565948
TI  - The levels of cockroach allergen in relation to cockroach species and allergic
      diseases in Thai patients.
AB  - Recently, cockroaches have been established as the second most Important
      allergen, producing allergic diseases, especially in low socioeconomic
      populations. In Thailand, about 44-61% of atopic patients were positive to
      cockroach extract by a skin-prick test. This study examined cockroach allergen
      levels in relation to cockroach species and allergic diseases in the houses of
      cockroach-sensitive patients. Sixty households of allergic patients in the
      Bangkok metropolitan area were surveyed using open- and closed-ended
      questionnaires. Cockroaches were collected using commercial cockroach traps,
      while dust samples were obtained from the bedrooms, kitchens and living rooms of
      the houses using a vacuum cleaner. The cockroaches were counted and their species
      Identified. The levels of cockroach allergens were determined by specific
      monoclonal antibodies using a monoclonal antibody-polyclonal antibody based
      sandwich ELISA kit. Six cockroach species were Identified: Periplaneta americana
      (American cockroach, 72.15%), Supella longlpalpa (2.75%, found in only one
      house), Periplaneta brunnea (0.78%), Periplaneta australaslae (0.78%),
      Neostylopyga rhombifolla (0.78%), Blattella germanica (German cockroach, 0.39%)
      and nymphs (22.35%). Allergens of the predominant species, P. americana, were
      detectable in all homes studied, with the highest levels in the kitchen areas.
      The range of allergen levels in house dust varied from 0.40-162.00 microg per g
      of dust. The median and mean allergen levels in kitchen dust were 59.16 microg
      and 62.80 microg per g of dust, respectively, while the median allergen level in
      bedroom dust was only 15.90 microg per g of dust. The German cockroach allergen
      (Bla g 2) was undetectable in any of the houses. IN CONCLUSION: P. americana was
      the most common cockroach and may be the species causing allergic diseases,
      especially asthma, in Thailand, which differs from the USA and Europe

PMID- 15565949
TI  - Allergenic pollen in the atmosphere of Kayseri, Turkey.
AB  - Airborne pollen are important allergens that cause sensitization in allergic
      rhinoconjunctivitis and asthma. Our aim was to detect the pollen in the
      atmosphere of Kayseri, to present a pollen calendar, and to detect the allergenic
      level of these pollen by performing skin tests on patients. Atmospheric pollen
      were collected by Durham gravimetric samplers in Kayseri between March and
      November in the years 1996 and 1997. In our study, we observed pollen belonging
      to 43 different taxa. The total number of pollen per cm2 was found to be 1,330.8
      in 1996 and 1,182.5 in 1997. Most of the pollen were from the taxa Pinus,
      Poaceae, Chenopodiaceae/Amaranthaceae, Cupressaceae, Populus and Quercus in
      decreasing order. In the skin tests, pollen of the taxa Poaceae and
      Chenopodiaceae were found to give the most frequent allergic reactions. It was
      concluded that preparing an airborne pollen calendar could be useful for medical
      practice. Nevertheless the skin test data did not really correlate with the
      aerobiologic data, as skin test reactivity is related to the allergenicity of the
      pollen and not just to ambient exposure.

PMID- 15565950
TI  - Somatropin promotes dermatophagoides farinae-specific IgE generation
      independently of IL-4 and IL-10.
AB  - Interleukin (IL)-10 accelerates the IgE production of anti-CD40- and IL-4
      stimulated PBMC by enhancing the IL-6 production of T lymphocytes or antigen
      primed spleen cells, in addition to its role as a regulator of the inflammatory
      responses. To further investigate the mechanisms enhancing IgE synthesis, we
      determined the effect of somatropin as well as IL-10 on the secretion of
      Dermatophagoides farinae (Df)-specific IgE by K7 cells, which originate from an
      EBV-immortalized cell line. Df-pulsed autologous T cells, as well as the
      supernatants of these cultures, increased the synthesis of Df-specific IgE.
      Antigen-specific IgE was also enhanced when K7 cells were treated with anti-CD40
      antibody and with both IL-4 and IL-10, or with IL-4 and IL-10 without anti-CD40
      antibody. The treatment of K7 cells with anti-CD40 antibody and IL-4, or anti
      CD40 antibody and IL-10 did not increase IgE production. The Df-specific IgE
      activity of the supernatants of K7 cells treated with somatropin alone was
      increased significantly although somatropin did not show any additive effect on
      the IgE production of anti-CD40 antibody-treated cells. The results indicate that
      IL-10, a Th2-type cytokine, directly affects the mature B cells that produce IgE,
      and that the secretion of IgE is increased by treatment with IL-10 in cells that
      are stimulated with anti-CD40 and IL-4 at the level of the EBV-immortalized cell
      line, which has already switched to IgE production. Somatropin similarly
      stimulates activated mature B cells to enhance their production of antigen
      specific IgE without class switching, independently of IL-4 and IL-10.

PMID- 15565951
TI  - HLA class II (DRB1, DQA1 and DQB1) allele and haplotype frequencies among HIV
      infection discordant Thai couples.
AB  - We investigated the association of HLA-DRB1, -DQA1 and -DQB1 alleles and
      haplotypes in 33 Thai HIV discordant couples. A significantly lower frequencies
      of DRB1*14 (3.0% vs 11.3%, p = 0.048) and DQA1*0103 (0.0% vs 5.63%, p = 0.042)
      alleles were found in the seropositive individuals when compared with HIV
      negative controls. In contrast, there was no significant difference in HLA-DQB1*
      allele frequencies. The haplotype analysis revealed that DRB1*1501-DQA1*0102
      DQB1*0601 (7.6% vs 0.0%, p = 0.002), DRB1*0405-DQA1*0302-DQB1*0401 (7.6% vs 1.3%,
      p = 0.024) and DRB1*1401-DQA1*0104-DQB1*05031 (6.1% vs 0.0%, p = 0.007) were
      found to be significantly higher frequencies when compared between HIV
      seronegative partners and HIV negative controls, but DRB1*1501-DQA1*0102
      DQB1*0502 (0.0% vs 8.1%, p = 0.01) was significantly lower. The DRB1*1602
      DQA1*0101-DQB1*0502 (4.6% vs 0.0%, p = 0.024) haplotype was found to be
      significantly higher frequencies in HIV seropositive individuals when compared to
      HIV negative controls but the DRB1*1502-DQA1*0101-DQB1*0501 (1.5% vs 8.1%, p =
      0.049) haplotype was lower.

PMID- 15565952
TI  - Genomic instability in scleroderma.
AB  - Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis.
      Cancer has an approximately two-fold higher incidence in scleroderma patients
      than in the general population. There are preliminary data of acquired genetic
      damage in scleroderma but the significance of these observations are uncertain.
      To determine somatic mutation frequency at the glycophorin-A (GPA) locus in
      patients with limited and diffuse cutaneous scleroderma. The GPA assay measures
      the total somatic mutation frequency (Vf), composed of gene inactivating
      mutations (NO) and mutations arising from mitotic recombination (NN) in
      individuals heterozygous for the GPA MN blood group. Mutation frequency was
      determined using a validated GPA flow cytometric assay using fluorescent labeled
      monoclonal antibodies specific for the GPA blood groups M and N. This assay
      detects and enumerates progeny of red blood cell (rbc) precursor cells which have
      acquired genetic damage resulting in a loss of expression of one of the GPA
      alleles. It was found that patients with scleroderma (n = 23) had significantly
      elevated Vf as compared with young healthy controls (p < 0.001) and elderly
      controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as
      compared with limited scleroderma (p = 0.055). In comparison with controls,
      patients with scleroderma exhibit a higher proportion of mitotic recombinant
      mutations than inactivating mutations (p < 0.002). There was no correlation
      between Vf and disease duration, age at onset or autoantibody status. We have
      documented evidence of acquired genetic damage at the GPA locus in scleroderma.
      Evidence of acquired genetic damage in this disorder may be importance in
      explaining both the etio-pathogenesis of scleroderma and the association of
      scleroderma with cancer.

PMID- 15565953
TI  - Association of the tumor necrosis factor alpha gene polymorphism with
      susceptibility and clinical-immunological findings of systemic lupus
      erythematosus.
AB  - The etiology of systemic lupus erythematosus (SLE) is unknown but genetic factors
      seem to play a role in the disease pathogenesis. The tumor necrosis factor alpha
      (TNFa) gene, encoded at the TNF locus in the MHC class III region, is now known
      to be an important candidate gene in SLE, due to the proinflammatory activities
      of the TNFa. The objectives of this study were to examine the role of the TNFa
      polymorphism for the susceptibility of Malaysian Chinese lupus patients to SLE
      and to determine its association with organ involvement. The allelic frequencies
      of the TNFa polymorphic variant (TNF2) of seventy lupus patients were determined
      during follow-up at the Medical Clinic of the National University Hospital
      Malaysia by PCR-RFLP technique. Sixty-four females and 6 males with a mean age of
      33+/-12 years were included. Clinical data were obtained from case records.
      Autoantibody levels were measured by ELISA. Fifty-nine ethnically-matched blood
      donors were used as controls. The allelic frequency of the TNF2 variant was found
      to be significantly increased in the patients compared to the controls (52.8% vs
      33.8%). SLE patients with the polymorphic TNF2 variant were found to be at
      increased risk of central nervous system involvement (p = 0.004, RR = 2.59) and
      to have an increased frequency of anti-La antibodies (p = 0.03). In view of these
      findings we suggest that TNF2 variant is playing a role in conferring
      susceptibility to SLE and in the disease pathogenesis.

PMID- 15565954
TI  - Undetectable plasma HIV-1 RNA with strong gag-pol specific interferon-gamma
      ELISPOT response in an HIV-1 clade A/E-infected child untreated with
      antiretroviral therapy.
AB  - We report a 7-year HIV-1 clade A/E-infected child untreated with antiretroviral
      therapy who had positive HIV antibody testing but undetectable plasma HIV-1 RNA
      by Roche Amplicor version 1.5 and bDNA version 3.0. DNA PCR was positive by
      methods using gag/pol primers but not env/pol primers. The patient had strong HIV
      1-specific cytotoxic T lymphocyte responses, which likely contributed to her low
      viral burden and undetectable plasma HIV-1 RNA.

PMID- 15565955
TI  - Sarcoidosis presenting as acute bilateral parotid swelling.
AB  - A case of bilateral parotid swelling of short duration, which turned out to be
      sarcoidosis confirmed by fine needle aspiration cytology, is presented here. The
      patient also had asymptomatic bilateral hilar lymphadenopathy and dryness of the
      eyes suggesting sarcoid involvement of the lungs and lacrimal glands. Sarcoidosis
      of the parotids, although rare, should be considered in the differential
      diagnosis of acute bilateral parotid swelling. Clinico-radiological findings of
      multi-organ involvement suggest the diagnosis in such cases.

PMID- 15565956
TI  - [Visions concerning medical and educational use of personal digital assistant].

PMID- 15565957
TI  - [Personal digital assistant].

PMID- 15565958
TI  - [Hyponatremia].

PMID- 15565959
TI  - [G receptor kinases. A family of "natural" receptor blockers].

PMID- 15565960
TI  - [Clinical-pharmacological counseling in Odense, 1997-2003].

PMID- 15565961
TI  - [Hyponatremia in acutely admitted medical patients--occurrence and causes].

PMID- 15565962
TI  - [Acute pancreatitis. Antibiotic prophylaxis in pancreatic necrosis?].

PMID- 15565963
TI  - [Physicians' skills with evidence-based medicine. Concepts, information retrieval
      and use].

PMID- 15565964
TI  - [Handheld computers in physicians' continuing education. Can and will physicians
      use them?].

PMID- 15565965
TI  - [Use of a combined mobile phone and fax solution in the selection of patients
      with S-elevation acute myocardial infarction].

PMID- 15565966
TI  - [Protection against enterotoxigenic Escherichia coli infections].

PMID- 15565967
TI  - [Urinary retention].

PMID- 15565968
TI  - [Terminal ileitis in a young man with Schoenlein-Henoch purpura].

PMID- 15565969
TI  - [Patients admitted to Rigshospitalet in 2003 on suspicion of having SARS. How
      were they diagnosed, and what illnesses did they have?].

PMID- 15565970
TI  - [Life-threatening obstruction of the airway caused by a herniated colon loop].

PMID- 15565971
TI  - [Axillary hyperhidrosis].

PMID- 15565972
TI  - [Quality and service--future main tasks in family practice?].

PMID- 15565973
TI  - Euthanasia, physician assisted suicide and other methods of helping along death.
AB  - This paper introduces a series of papers dealing with the topic of euthanasia as
      an introduction to a variety of attitudes by health-care professionals and
      philosophers interested in this issue. The lead in paper--and really the lead in
      idea--stresses the fact that what we are discussing concerns only a minority of
      people lucky enough to live in conditions of acceptable sanitation and who have
      access to medical care. The topic of euthanasia and PAS really has three
      questions: (1) is killing another ever ethically acceptable; (2) is the
      participation of health professionals ethically different and (3) is it wiser to
      permit and set criteria (being fully aware of some dangers that lurk in such a
      move) or to forbid (knowing that it will occur clandestinely and uncontrolled).
      This paper takes no definite stand although it is very troubled by useless
      suffering (not only pain) by many who would wish their life and with it their
      suffering ended.

PMID- 15565974
TI  - Euthanasia and palliative care in The Netherlands: an analysis of the latest
      developments.
AB  - This article discusses the latest developments regarding euthanasia and
      palliative care in The Netherlands. On the one hand, a legally codified practice
      of euthanasia has been established. On the other hand, there has been a strong
      development of palliative care. The combination of these simultaneous processes
      seems to be rather unique. This contribution first focuses on these remarkable
      developments. Subsequently, the analysis concentrates on the question of how
      these new developments have influenced the ethical debate.

PMID- 15565975
TI  - An academic internist looks at euthanasia.
AB  - This paper points out that to persons unfamiliar with the context and suffering
      of dying patients, their loved ones, and last, but by no means least, the health
      care team can only discuss the very concrete question of euthanasia in an
      abstract way unaware of the fact that this question must, in the final analysis,
      be differently addressed in different specific patients and under specific
      circumstances. This paper poses questions which must be addressed and will rarely
      find a good answer but at least the best among a series of unpalatable options.
      It again points out the important and legitimate place that emotions play in
      decision-making.

PMID- 15565976
TI  - One physician's perspective: euthanasia and physician-assisted suicide.
AB  - This paper looks at the ambiguities which PAS (physician assisted suicide) and
      voluntary active euthanasia (VAE ) present to the patient, his or her loved ones
      and the health-care team. The author pleads for a greater emphasis on humanizing
      the experience of the dying so that a team can meet their physical, emotional and
      spiritual needs.

PMID- 15565977
TI  - Voluntary active euthanasia and the doctrine of double effect: a view from
      Germany.
AB  - This paper discusses physician-assisted suicide (PAS) and voluntary active
      euthanasia (VAE), supplies a short history and argues in favour of permitting
      both once rigid criteria have been set and the cases retro-reviewed. I suggest
      that among these criteria should be that VAE should only be permitted with one
      more necessary criterion: that VAE should only be allowed when physician assisted
      suicide is not a possible option. If the patient is able to ingest and absorb the
      medication there is no reason why VAE should be permitted. A brief history of VAE
      and PAS is given and some of the arguments which have been given are analyzed.
      The Principle of the Double Effect is briefly discussed and why, in my opinion,
      it is not a valid principle is briefly discussed.

PMID- 15565978
TI  - Hastening death by selective disclosure of treatment options--beneficence or
      "euthanasia by deception"?
AB  - In this paper I make a radical claim regarding selective non-disclosure of
      treatment options that have some hope of prolonging a patient's life. I suggest
      that selective non-disclosure under such circumstances is tantamount to what
      might be called "euthanasia by deception." I offer a case to test the validity of
      my claim and to demonstrate how the failure to offer or, at least, to discuss
      renal dialysis in this case (and, by inference, any other form of treatment which
      has some hope of prolonging a patient's life) qualifies as paternalism in its
      most egregious form. I discuss the actions of the health care team and try to
      find some plausible reasons why they acted as they did. I conclude that there
      must be greater emphasis placed on teaching clinicians how better to incorporate
      frank, open and on-going discussion about the central elements of the therapeutic
      relationship with patients long before they lose decisional capacity.

PMID- 15565979
TI  - [Adolescent depression--a serious disease].

PMID- 15565980
TI  - [Urinary incontinence in older man].

PMID- 15565981
TI  - [Is the treatment of hypertension is changing?].

PMID- 15565982
TI  - [Imaging of scoliosis].

PMID- 15565983
TI  - [Shaken baby syndrome].

PMID- 15565984
TI  - [Does community involvement promote health?].

PMID- 15565985
TI  - [Targeted anticancer drugs and their development].

PMID- 15565986
TI  - [Gastric bypass surgery as treatment for morbid obesity].

PMID- 15565987
TI  - [Spontaneous coronary artery dissection in the course of myocardial infarction].

PMID- 15565988
TI  - [Smoking cessation].

PMID- 15565989
TI  - [From animal models to human trials of Peutz-Jeghers syndrome].

PMID- 15565990
TI  - [Liposuction as treatment of diabetes--is it an effective treatment?].

PMID- 15565991
TI  - [Erythema and skin rash as symptoms due to bone fracture].

PMID- 15565992
TI  - [Relationship between development of hypertension and a family history of high
      blood pressure in urban residents-analysis based on results of annual health
      examinations, 1984 to 1998].
AB  - Relationship between development of hypertension and a family history of high
      blood pressure in urban residents-analysis based on results of annual health
      examinations, 1984 to 1998. OBJECTIVE: To clarify the relationship between
      development of hypertension and a family history of this condition in urban
      residents. METHODS: Findings from a 15-year follow-up study of annual health
      examinations carried out in a community adjoining Osaka city, from 1984 to 1998,
      were analyzed. Any person who indicated in a self-administered questionnaire that
      they had either a parent or a sibling with hypertension was considered as having
      a family history of hypertension. RESULTS: In each year analyzed, mean systolic
      and diastolic blood pressure, by both sex and age group, was generally higher for
      those with a family history of hypertension than those without. We examined the
      proportion of people with such a family history and found that among those who
      received examinations for 5 consecutive years, the number of times at which the
      proved normotensive was generally lower than in the control group. When we looked
      at the odds ratio for hypertension according to combinations of family history,
      obesity, and use of alcohol, those with all three risk factors had the largest
      values in each year, followed by those with a family history plus obesity, but
      without drinking. The population attributable risks were 6.6%-16.0% for family
      history in men and 6.6%-18.4% in women, 6.0%-18.1% and 9.0%-25.2% for obesity and
      3.5%-29.4% and 0.3%-4.0% for drinking. These results show that the tree
      distributions of normotensiven (optimal, normal, high-normal) were normotensive
      overall the first time (1984), and for those who received examinations in 1993
      and 1998, hazard ratios with a positive family history were higher than with a
      negative family history. CONCLUSIONS: The main new findings of this study are
      that the incidence of hypertension is significantly higher in people with a
      family history of the disease than in those without, and looking at odds ratios
      for population attributable risk, family history proved to be a factor almost as
      important for high blood pressure as obesity and drinking. The results indicate
      family history is a significant risk factor for hypertension.

PMID- 15565993
TI  - [Development of a Japanese version of the Subjective Happiness Scale (SHS), and
      examination of its validity and reliability].
AB  - OBJECTIVES: The purpose of the present study was to develop a Japanese version of
      the Subjective Happiness Scale (SHS) and to examine its validity and reliability.
      METHODS: The four items of the English SHS were translated into Japanese. These
      Japanese items were back-translated into English, and verified by one of the
      developers of the original SHS. The participants were 364 Japanese undergraduate
      students (158 males and 206 females). They were asked to answer the questionnaire
      including the Japanese SHS, five items concerning positive health and self
      esteem, and the Japanese General Health Questionnaire (GHQ). The stability of the
      Japanese SHS was examined over a five-week time period. RESULTS: It was shown
      that the Japanese SHS was highly internal consistent with alphas of .80 for males
      and .84 for females. As for the test-rest reliability, a high correlation (r =
      .86) was found after five-week. One factor structure and factor loadings emerged
      clearly from factor analysis. The scores of the Japanese SHS correlated
      positively with positive health and self-esteem. Furthermore, they were
      significantly greater in the healthy group than in the unhealthy one, from the
      GHQ scores, especially for depression. CONCLUSIONS: These findings suggest that
      the Japanese version of SHS has internal consistency, test-retest reliability,
      convergent validity, and discriminant validity.

PMID- 15565994
TI  - [Individual background factors for "cannot go out alone to distant places" among
      medium elderly persons living alone in a metropolitan suburb].
AB  - OBJECTIVE: To verify whether the statement "cannot go out alone to distant
      places" should be considered a risk factor for disability among medium elderly
      persons living alone autonomously in a metropolitan suburban environment, the
      present cross-sectional study was performed. METHODS: Self-rated mobility levels
      in elderly persons living alone were surveyed by questionnaire in 1,216 elderly
      people (209 male, 1007 female) aged 65 to 74 years, living in a metropolitan
      suburb, who had autonomy and ambulation competence. Two categories were used for
      evaluation of the self-rated mobility level: the A group were those who were able
      to go out alone to distant places and the B group were those who were able to do
      so in the locality, but not to distant places without help (cannot go out alone
      to distant places). Factors such as everyday lifestyle, self-rated health, and
      psychological, functional, physical and social items were investigated. RESULTS:
      Although the frequency of going out was nearly the same between the A and B
      groups, the B group showed the lower hobby and association activity in social
      communities. Individual factors such as self-rated health, instrumental
      activities of daily living (Tokyo Metropolitan Institute of Gerontology),
      eyesight, masticatory ability, 1 km continuous walking, pedestrian crossing
      walking on a green light, and fracture history, medicine intake, cerebrovascular
      disorder related subjective symptoms, intermittent claudication related
      subjective symptoms, physical pain, symptoms of depression, daytime sleep, number
      of meals, and no regular walking and light gymnastic exercises demonstrated
      significant differences in levels between the A and B groups. The B group had
      characteristics of lower social activities in social communities, deterioration
      of physical functions, subjective symptoms of sickness and depression, and a
      worse self-rated level of health. On stepwise multiple logistic regression
      analysis, individual frailty-risk factors related to "cannot go out alone to
      distant places", were "inability to continuously walk a distance of 1 km", "lower
      masticatory ability", "having depressive symptoms", and "having symptoms of
      intermittent claudication". CONCLUSIONS: The findings from this study show that
      with autonomous medium elderly persons, those who "cannot go out alone to distant
      places" have risk factors for a trend toward disability.

PMID- 15565995
TI  - [Development and effects of a health promotion program utilizing the mail
      function of mobile phones].
AB  - PURPOSE: The purpose of the study was to develop a health education program,
      named "i-exerM," utilizing the mail function of the mobile phone and affect its
      effects setting body weight reduction as the achievement target. METHODS: The i
      exerM was developed with 136 adults (28 males and 108 females) living or working
      in Shizuoka Prefecture, and subscribing to the i-mode of NTT DoCoMo orJ-sky of
      JPHONE (currently Vodafone), who indicated an interest in participating in a body
      weight reduction twelve week (between July 15th and October 9th, 2003) program.
      As-one of the special characteristics of the i-exerM, the subjects were informed
      once every day via mailing to the mobile phone some new items regarding body
      weight reduction knowledge and practice. By use of a self-monitoring method, the
      subjects were asked to register the body weight via internet from time to time.
      Information for each individual at the start and the end of the i-exerM
      monitoring session was collected with a questionnaire covering physical
      conditions, lifestyle and program evaluation, without an meeting with the
      participants during the program. From this trial result, the enforcement
      potential of healthy education utilizing the mail function of mobile phones was
      examined. RESULTS: 1) Those who submitted a questionnaire before the i-exerM
      start and after the end were 14 adult (50%) males and 69 adult (64%) females. 2)
      A tendency for reduced body weight was found in 63 (46%) of 136 adults who
      participated in the i-exerM. Furthermore, average body weights were significantly
      reduced (P < 0.001) from 73.2 kg to 71.1 kg (males), and from 58.8 kg to 57.6 kg
      (females). 3) The i-exerM program was evaluated positively, 44 adults (32%)
      indicating that it was "greatly effective" for "stimulating consideration of body
      reduction and starting concrete efforts." CONCLUSION: The success of the current
      i-exerM program suggests its possible application for chronic disease states such
      as hypertension and hyperlipidemia.

PMID- 15565996
TI  - [Time study of nurse's shift work the influence of domestic labor on fatigue
      after ordinary labor].
AB  - INTRODUCTION: The relationship between domestic labor and fatigue following night
      shift work by nurses was examined. Differences due to the age of the youngest
      child, which apparently influences housework time, were analyzed. METHODS: A time
      survey was conducted with 159 shift work nurses at a public general hospital.
      Participants were divided into three groups based on the age of the youngest
      child, i.e., those whose youngest child was in school were placed in the "school
      age" group, those whose youngest child was preschool age were placed in the
      "preschool age" group, and nurses without children were placed in the "childless"
      group. Using four categories of daily living, time use was set as labor hours,
      physiological hours, house work hours, and social and cultural activity hours,
      and daily living time was described with reference to seventeen items. A
      subjective symptoms index (SSI) was applied after both day and night shifts.
      Comparison of the degree of recovery from physical fatigue and loss of mental
      concentration were also investigated between the end of day work and the start of
      night work. RESULTS: Sleeping and napping time was 7 hours and 53 minutes in the
      "preschool age" group, 8 hours and 18 minutes in the "school age" group, and 9
      hours and 11 minutes in the "childless" group. Housework time was 3 hours and 9
      minutes in the "preschool age" group, 2 hours and 1 minute in the "school age"
      group, and 48 minutes in the "childless" group, with the majority of time spent
      doing cooking and childcare chores. Social and cultural activity time was 36
      minutes in the "preschool age" group, 57 minutes in the "school age" group, and 1
      hour and 19 minutes in the "childless" group. Fireside time with family was a
      mere 7 minutes in the "preschool age" group. The subjective symptoms index (SSI)
      after night work showed severe fatigue in all groups. All groups showed greater
      fatigue and loss of concentration at the time of night work than when finishing
      day work. DISCUSSION: The results showed greater fatigue in the "preschool age"
      group, which suggests an inverse correlation with sleeping and napping and a
      positive link to labor in the home. The "preschool age" group had longer
      housework hours, and shorter sleeping and social and cultural activity hours,
      which are presumed to influence fatigue.

PMID- 15565997
TI  - [WHO definition of health: a historical perspective].

PMID- 15565998
TI  - [Clinical analyses of Aspergillus infections in patients with underlying
      pulmonary disease].
AB  - To elucidate the clinical features of Aspergillus infections with underlying
      pulmonary disease, we analyzed 79 cases with positive results for anti
      aspergillus antibody. The patients were 69 men and 10 women. Mean age at
      diagnosis was 68.0. Positive rates for isolation of Aspergillus spp. from the
      airways, and of galactomannan antigen and 1, 3-beta-D glucan in the serum were
      44.3, 21.8, 26.5%, respectively. These findings did not show any differences
      according to underlying pulmonary disease. Twenty-nine patients died of the
      disease. Body mass indices, serum albumin levels and red blood cell counts were
      significantly lower in the patients who died. Extension of the lesion to the
      lower lobes or to 3 or more lobes was correlated significantly with poor
      survival. A specific diagnostic tool was required for early detection of the
      disease.

PMID- 15565999
TI  - [Study of administration times and clinical efficacy of carbapenems in the
      treatment of moderate community-acquired bacterial pneumonia].
AB  - The half-lives of carbapenems are about 1 hour. It was expected that increasing
      the daily frequency of administration would improve the clinical effects. We
      therefore studied the clinical effects of increasing the daily administration
      frequency of meropenem in the treatment of community-acquired bacterial
      pneumonia. The subjects were patients with moderate community-acquired bacterial
      pneumonia who were aged less than 75 years. They were divided into a BID group
      (28 patients receiving 0.5 g morning and evening) and a TID group (27 patients
      receiving 0.25 g in the morning and about midday, and 0.5 g in the evening), and
      the clinical effects were reviewed prospectively. Clinical efficacy on the third
      day was 78.6% in the BID group and 85.2% in the TID group, and over-all clinical
      efficacy was 89.3% in the BID group and 88.9% in the TID group. Administration
      periods were 12.8 +/- 4.2 days in the BID group and 10.9 +/- 3.4 days in the TID
      group. These results show no statistically significant difference, and suggest
      that the excellent clinical effect of administration of MEPM 0.5 g twice a day on
      moderate community-acquired bacterial pneumonia is not improved by administration
      three times a day.

PMID- 15566000
TI  - [Outcome of pulmonary Mycobacterium avium complex (MAC) disease treated with
      clarithromycin (CAM)-containing regimens].
AB  - We retrospectively investigated the efficacy of regimens including clarithromycin
      (CAM) in 129 patients with Mycobacterium avium complex (MAC) pulmonary disease
      and their outcomes. None of the patients suffered from acquired immunodeficiency
      syndrome. All were observed for over 12 months. We studied the factors that may
      affect sputum conversion and fatal outcomes by logistic regression analysis. The
      results indicated that the presence of either cavitation or bronchiectasis was
      significantly correlated with persistent MAC-positive culture results in sputum
      (Odds ratio, 4.71, 95%; CL, 1.21-18.5; P<0.05). Regimens including
      antituberculous drugs and CAM were administered to 118 patients, 11 of whom
      received CAM alone because of the adverse events of antituberculous agents. There
      was no difference in sputum conversion or mortality between the two groups,
      suggesting that the pattern of drug combination should be further investigated.

PMID- 15566001
TI  - [Eosinophilic airway disorders: important causes of prolonged cough in Japan].
AB  - We studied 223 outpatients who presented between October 2001 and June 2003 with
      persistent cough of more than 3 weeks' duration. Eosinophilic airway disorders
      (EAD), including atopic cough and cough variant asthma, were clinically diagnosed
      in 119 patients, on the basis of the following factors: history of atopic
      disease, duration of cough, history of previous prolonged cough, or presence of
      forced expiration wheeze. Since eosinophils are frequently found in the sputum of
      patients with EAD, a positive test strongly suggests the presence of EAD. In this
      study, the test was positive in 86% of the patients with EAD. The patients with
      clinically diagnosed EAD, including those with no eosinophils in the sputum, were
      treated with inhaled fluticasone 400 or 800 microg/day. Fluticasone was effective
      in 97% of the patients with EAD and was more effective than bronchodilators or
      antiallergic drugs. When we compared the results of fluticasone 400 microg/day
      with those of 800 microg/day doses, the cough disappeared within 1 week in 28% of
      the patients who received 400 microg/day, whereas in 76% with 800 microg/day.
      Among the patients with diagnosed EAD, bronchial asthma developed in 6 patients
      during the observation period. Most of these patients had forced expiration
      wheeze and lower FEV 1 at the initial visit. This study showed that EAD could be
      diagnosed in the early stage on the basis of thorough history-taking, the
      presence of forced expiration wheeze and detection of eosinophils in the sputum.
      It is important to diagnose and treat EAD as early as possible since inhaled
      steroid is highly effective.

PMID- 15566002
TI  - [Usefulness of low-dose single-slice CT (SSCT) for mass screening to detect
      various thoracic diseases including lung cancer].
AB  - This study assessed the usefulness of SSCT for mass screening retrospectively in
      8885 subjects (6781 men, 2104 women) who had received mass screening to detect
      thoracic disease by using SSCT from 1999 to 2003. In the 8885, 119 (1.3%) lesions
      were detected as active thoracic disease. These 119 lesions comprised 39
      neoplasms and 80 instances of non-neoplastic disease. Of those with neoplastic
      lesions, 25 had lung cancer (adenocarcinomas, 20; Squamous, 3; carcinoids, 2), 7
      had mediastinal tumors and 7, others. Non-neoplastic cases comprised 39 of COPD
      (pulmonary emphysema), 17 of pulmonary tuberculosis, 8 of non-tuberculous
      mycobacteriosis and 16 others. Surgical treatment was performed in 46 cases: 25
      of lung cancer, 14 of non-cancerous neoplasms, 3 of pulmonary sequestration and 4
      others. In the lung cancer cases, the post-surgical staging was I or II (stage I,
      20; stage II, 5). Low-attenuation areas (LAA) were seen on multiple CT slices in
      2.2% of all subjects (195). These 195 cases had no respiratory symptoms such as
      exertional dyspnea, But 39 of them had an FEV1.0% (FEV1.0/FVC) of less than 70%.
      All 39 had a history of smoking, We suggested that SSCT screening is a useful
      method of mass screening to detect thoracic neoplastic lesions as well as non
      neoplastic lesions.

PMID- 15566003
TI  - [A case of pulmonary nocardiosis with a polypoid lesion in a bronchus].
AB  - A 62-year-old woman was admitted with fever and bloody sputum. A mass shadow in
      the left S3 and obstruction of the left B3 were seen on a chest radiograph and
      CT. Obstructive pneumonia was suspected, and cefotiam and imipenem/cilastatin
      were administered. However, this treatment did not show adequate efficacy.
      Bronchoscopy demonstrated a yellowish-white polypoid lesion in the left B3, but
      histopathological findings with HE staining yielded no definite diagnosis.
      Subsequently, Nocardia asteroides was detected in sputum test. A sulfamethoxazole
      trimethoprim combination and minocycline were administered, and the clinical
      findings improved. Gram-positive microfilaments were confirmed retrospectively in
      the pathologic specimen, and a diagnosis of pulmonary nocardiosis was made.

PMID- 15566004
TI  - [Three cases of angiosarcoma complicated with chronic pleuritis].
AB  - We report three cases of angiosarcoma complicated with chronic pleuritis
      associated with tuberculosis. Patient 1 was a 55-year-old man who had received
      artificial pneumothorax therapy 30 years before. Patient 2 was a 85-year-old man
      who had suffered from pleuritis for 10 years; and patient 3 was a 72-year-old man
      who had received plombage thoracoplasty with plastic balls 40 years before. All
      cases had began with sudden-onset chest pain and bloody sputa. A surgical
      procedure was indicated in patient 1 only. Conservative therapy was indicated for
      the other cases because of aging, performance status and systemic metastasis.
      Prognoses from the onset were 83, 9 and 1 months, respectively. We concluded that
      angiosarcoma is a disease of equal importance as a malignant tumor to lymphomas
      appearing in the course of chronic inflammatory diseases such as chronic empyema,
      and that only aggressive resection, when it is possible, is effective in offering
      prolonged survival.

PMID- 15566005
TI  - [A case of pyogenic spondylitis mimicking a spinal invasion of lung cancer].
AB  - A 58-year old man was admitted to our hospital complaining of right back pain,
      fever, abdominal fullness and epigastralgia. Chest CT revealed a mass shadow in
      the right S6 together with destruction of the thoracic vertebrae. These findings
      suggested lung cancer and its spinal invasion. A transbronchial lung biopsy
      specimen showed inflammatory lymphocyte infiltration. MRI T2 image of the spine
      showed a high intensity at the Th7/8 disc space, suggesting pyogenic spondylitis.
      After broad-spectrum antibiotics including PAMP/BP and CLDM were administered,
      both the spinal lesion and the pulmonary lesion improved gradually. The clinical
      course suggested that the pulmonary inflammatory lesion had spread from pyogenic
      spondylitis. In our case, the pyogenic spondylitis was mimicking a spinal
      invasion of lung cancer. In addition, MRI is thought to be useful for diagnosing
      spinal lesions.

PMID- 15566006
TI  - [Epidural, mediastinal and subcutaneous emphysema in a patient with suspected
      torme fruste of Marfan syndrome].
AB  - A 17 year-old youth presented with swelling of both sides of neck after a fight
      with a friend. He had been sick with an upper respiratory tract infection for a
      few days with frequent coughing. Chest radiography showed subcutaneous and
      mediastinal emphysema. Neck CT at the level of C7 showed air around the trachea,
      extending to the subcutaneous tissue and the epidural space through the
      intervertebral foramen. His height was 180 cm and his weight 55 kg, and he had a
      181 cm arm span. He had scoliosis and arachnodactyly, and ultrasonic cardiography
      demonstrated mitral and tricuspid regurgitation. These findings agreed partially
      with the clinical criteria of Marfan syndrome. Thus, forme fruste of Marfan
      syndrome was suspected. A rapid rise of airway pressure induced by a coughing
      attack and loud shouting during the fight probably caused the laceration of the
      connective tissue in the airway, resulting in mediastinal and epidural emphysema.
      In this case report, CT at the C7 level satisfactorily identified air in the
      mediastinum extending to the epidural space through intervertebral foramen.

PMID- 15566007
TI  - [Severe asthma complicated with large mucoid impaction: successful removal with
      balloon catheter].
AB  - A 28-year-old woman was hospitalized for renal transplantation. She suffered an
      asthma attack after transplantation. Once this attack had ended after medical
      treatment, she again experienced dyspnea after the 11th treatment day. A chest CT
      showed mucoid impaction in the left main bronchus, atelectasis in the left lower
      lobe, and pneumomediastinum. A huge mucoid impaction was removed with a balloon
      catheter under mechanical ventilation without exacerbation of the mediastinal
      emphysema. Mucoid impaction should be taken into account as a cause of dyspnea in
      severe asthma if the maximum dose of beta-stimulant is not effective.

PMID- 15566008
TI  - [A case of bronchial ulcer due to infection by Mycobacterium abscessus].
AB  - We present a rare case of tracheobronchitis caused by Mycobacterium abscessus.
      The patient was a 79-year-old man with a previous history of tuberculosis. For
      smear examinations, he repeatedly expectorated many acid-fast bacilli.
      Bronchoscopic examination revealed the presence of ulceration on the lower end of
      the trachea and extending to the right main bronchus. Mycobacterial cultures were
      used to grow Mycobacterium abscessus. Following an antimicrobial regimen of
      clarithromycin, amikacin, and cefoxitin, the patient exhibited marked
      improvement. After initial multidrug therapy, the patient was placed on
      clarithromycin for 10 months. No relapse has occurred to date.

PMID- 15566009
TI  - [A case of pulmonary Langerhans' cell histiocytosis with liver involvement].
AB  - We report a case of pulmonary Langerhans' cell histiocytosis with liver
      involvement in an adult. An asymptomatic 51-year-old man who had, until his
      referral to our hospital, been a smoker was suspected on examination to have
      multiple metastases to the lungs and liver. Chest CT showed multiple
      micronodules, located predominantly in the upper and middle lung fields. Many of
      these nodules were cavitary. Abdominal US showed multiple, well-defined, round
      and oval nodules of decreased echogenicity within the liver. Hepatic nodules were
      enhanced rapidly by contrast-enhanced CT. Comparatively large nodules were
      demonstrated as well-circumscribed hypoattenuating lesions with ring enhancement.
      Since further work-up did not demonstrate any evidence of malignancy, open lung
      biopsy was performed. The results of open lung biopsy were consistent with
      Langerhans' cell histiocytosis. The infiltrates consisted of variable numbers of
      Langerhans' cells with folded nuclei and eosinophils. Immunohistochemically, the
      histiocytes were positive for S-100 protein and CD1a, and negative for CD68. The
      nodules regressed within 5 months after smoking cessation, and the patient became
      free of disease 10 months after the initial presentation.

PMID- 15566010
TI  - Physical exercise and experienced bodily changes: the emergence of benefits and
      limits on benefits.
AB  - Self-reports of levels of physical exercise, experienced bodily changes, and
      attitudinal and well-being variables were obtained from 407 adults, aged 26 to 95
      years. The purpose was to assess the relative magnitudes of the experienced
      benefits of exercise across the exercise continuum. Cluster analyses identified
      three groups at each of four age levels: a) sedentary people who experienced
      negative bodily changes; b) modest exercisers who reported the most positive
      bodily changes; and c) high exercisers who reported only minimal bodily changes.
      Psychological barriers to exercise among sedentary people included negative
      exercise attitudes, attributions of negative bodily changes to aging, and low
      levels of exercise motivation and self-efficacy. Modest and high exercisers both
      scored high on attitude and well-being variables.

PMID- 15566011
TI  - The attainment of important health goals throughout adulthood: an integration of
      the theory of planned behavior and aspects of social support.
AB  - This research integrates the Theory of Planned Behavior (TPB) with aspects of
      social support and explores the utility of variables within each model in
      predicting the attainment of important health goals. Incorporating an idiographic
      methodology, 290 respondents ranging in age from 27 to 87 years were administered
      a postal survey and completed a brief follow-up telephone survey months later.
      The postal survey included measures of respondent's most important health goals,
      attitudes, motivation to comply with subjective norms, control beliefs,
      behavioral intention, and plan-of-action for attaining the health goal, as well
      as aspects of social support. The follow-up telephone survey inquired into
      respondents' successful goal attainment and health. Results indicate association,
      between TPB components and aspects of social support. Further, the emotional and
      instrumental support provided by a family member or friend and size of social
      support network were found to be unique predictors of health goal attainment
      after controlling for TPB components. The importance of personalized goals and
      social support in designing health interventions for older adults is discussed.

PMID- 15566012
TI  - Practical memory concerns in adulthood.
AB  - In this article, we focus on practical memory concerns in adulthood. Young,
      middle-aged, and community-dwelling older adults responded to seven open-ended
      questions covering the topics of memory self-efficacy, memory management, memory
      remediation, and fears about memory aging in adulthood. The results revealed
      several similarities among the age groups. All groups reported the same types of
      information as easy to recall, and responses across age groups were also largely
      alike in terms of mnemonics usage, forgetting that is bothersome, and forgetting
      that is not bothersome. Differences between the age groups were most evident in
      responses related to types of information that are difficult to recall, areas of
      memory where improvement is desired, and fears of memory aging. Implications for
      understanding adult memory concerns and memory beliefs across the adult lifespan
      are discussed.

PMID- 15566013
TI  - Race, gender, and the retirement decisions of people ages 60 to 80: prospects for
      age integration in employment.
AB  - Demographic projections have prompted concerns about the potential economic
      burden of an aging population. This article, drawing on the 1998 Health and
      Retirement Study, explores ways in which race, gender, and age moderate the
      effects of various factors on labor force participation among people ages 60 to
      80. Key findings center on health, education, and non-wage income. First, the
      effect of low non-wage income is weaker at older ages due to higher levels of
      functional disability. Second, the effect of low education is stronger for women,
      who perceive their chances of finding employment as low. Third, the effect of
      health is weaker for blacks, as they are less likely to find steady employment
      regardless of health. POLICY IMPLICATIONS: Employer flexibility in number of
      hours worked might make sense for workers close to retirement age, while job
      search and training programs might be preferable for workers past the typical
      retirement age.

PMID- 15566014
TI  - HIV/HCV coinfection in clinical practice.
AB  - Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) frequently co
      exist due to shared routes of transmission. In the past, the impact of HCV on
      overall morbidity and mortality of coinfected patients was minimal due to the
      poor prognosis of HIV. However, since the introduction of highly active
      antiretroviral therapy (HAART), HCV has become a significant pathogen in this
      population. HIV clearly exacerbates HCV infection and accelerates progression to
      cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There is debate
      over whether HCV influences the natural history of HIV. Given the high prevalence
      of coinfection and the accelerated liver damage, HCV treatment has become a
      priority in these patients. There are new data on pegylated interferon (PEG-IFN)
      and ribavirin (RBV) therapy for HCV in coinfected patients. The therapy is well
      tolerated and safe, although it appears to be slightly less effective than in
      monoinfected patients. The risk of HAART-related hepatotoxicity is greater in
      coinfected patients and therefore requires special consideration and close
      monitoring.

PMID- 15566015
TI  - Correlation between healthcare workers' knowledge of influenza vaccine and
      vaccine receipt.

PMID- 15566016
TI  - An estimate of the incidence of Candiduria among hospitalized patients in the
      United States.

PMID- 15566017
TI  - Bacteria of nosocomial urinary tract infections at a university hospital in
      Egypt: identification and associated risk factors.

PMID- 15566018
TI  - Assessment of a novel approach to evaluate the outcome of endoscope reprocessing.

PMID- 15566019
TI  - Epidemic parenteral exposure to volatile sulfur-containing compounds at a
      hemodialysis center.

PMID- 15566020
TI  - Influenza and pneumococcal vaccination: how far we have come and how to go
      farther.

PMID- 15566021
TI  - Improving the rates of inpatient pneumococcal vaccination: impact of standing
      orders versus computerized reminders to physicians.
AB  - OBJECTIVE: To determine the impact of interventions using standing orders and
      computerized reminders to physicians on inpatient pneumococcal vaccination rates
      relative to a control group. DESIGN: Open trial of the following approaches, each
      on a different ward: (1) standing orders for vaccination of eligible consenting
      patients, (2) computerized reminders to physicians, and (3) usual practice.
      SETTING AND PATIENTS: Four hundred twenty-four patients were admitted to three 30
      bed inpatient medical wards during a 4-month period in 1999 at one hospital.
      Unvaccinated patients 65 years or older and competent to give oral consent were
      included. INTERVENTION: A pharmacist activated a standing orders protocol for
      vaccination of all eligible consenting patients on one ward and computerized
      reminders to physicians on a second ward. A third ward served as a control group.
      RESULTS: Forty-two patients met inclusion criteria and accepted vaccination in
      the standing orders arm versus 35 patients in the computerized reminder arm.
      Vaccination rates on the standing orders ward included 98% of those eligible and
      accepting vaccination, 73% of eligible patients, and 28% of all patients
      admitted. Rates on the computerized reminder ward were 23%, 15%, and 7%,
      respectively. All of the rates from the standing orders ward were significantly
      greater than those from the computerized reminder ward (P < .0001). Only 0.6% of
      all patients on the control arm were vaccinated. CONCLUSION: Although both
      interventions were effective in increasing inpatient pneumococcal vaccination
      rates relative to baseline practice, physician independent initiation of standing
      orders was clearly more effective.

PMID- 15566022
TI  - Policies and practices for improving influenza immunization rates among
      healthcare workers.
AB  - OBJECTIVE: To determine the attitudes, policies, and barriers for requiring
      annual versus voluntary influenza vaccinations for the staff of healthcare
      institutions in North Carolina. METHODS: Five different types of institutions
      serving at-risk elderly populations throughout North Carolina were chosen for
      study, including hospitals, home health agencies, nursing homes, dialysis
      centers, and assisted living facilities. Infection control managers completed a
      45-question telephone survey on policies for annual influenza vaccinations for
      employees, incentives to encourage immunizations, support for mandatory influenza
      vaccinations for workers, barriers to employee vaccinations, and support for a
      state law to mandate influenza immunizations for employees with patient care
      contact. RESULTS: Of 312 institutions, 268 (86%) participated in the study. Only
      38% of institutions reported having formal written employee influenza vaccination
      policies, and only 2% actually mandated annual employee vaccinations. Reported
      barriers to increasing healthcare worker annual influenza vaccinations included
      "fear of side effects" and "perceived ineffectiveness of the flu vaccine." Almost
      half of the respondents would support mandating influenza vaccinations for all
      healthcare workers with direct patient contact. CONCLUSION: A state-wide survey
      of the receptivity, policies, and implications of mandated employee influenza
      vaccinations among healthcare institutions serving the elderly in North Carolina
      found written policies uncommon and most of the mechanisms used to increase
      vaccinations voluntary. Efforts should be tailored to individuals, institutions,
      and healthcare systems to dramatically increase employee immunization rates.

PMID- 15566023
TI  - Improving influenza immunization rates among healthcare workers caring for high
      risk pediatric patients.
AB  - OBJECTIVE: To assess influenza vaccination rates of healthcare workers (HCWs) in
      neonatal intensive care units (NICUs), pediatric intensive care units (PICUs),
      and oncology units in Pediatric Prevention Network (PPN) hospitals. PARTICIPANTS:
      Infection control practitioners and HCWs in NICUs, PICUs, and oncology units.
      METHODS: In November 2000, posters, electronic copies of a slide presentation,
      and an influenza fact sheet were distributed to 32 of 76 PPN hospitals. In
      January 2001, a survey was distributed to PPN hospital participants to obtain
      information about the immunization campaigns. On February 7, 2001, a survey of
      influenza immunization was conducted among HCWs in NICU, PICU, and oncology units
      at participating hospitals. RESULTS: Infection control practitioners from 19
      (25%) of the 76 PPN hospitals completed the surveys. The median influenza
      immunization rate was 43% (range, 12% to 63%), with 7 hospitals exceeding 50%.
      HCWs (n = 1123) at 15 PPN hospitals completed a survey; 53% of HCWs reported
      receiving influenza immunization. Immunization rates varied by work site: 52% in
      NICUs and PICUs compared with 60% in oncology units. Mobile carts and PPN
      educational fact cards were associated with higher rates among these
      subpopulations (P < .001) (361 [63%] of 575 vs 236 [44%] of 541 for mobile carts;
      378 [60%] of 633 vs 219 [45%] of 483 for fact cards). CONCLUSION: Despite delayed
      distribution of influenza vaccine during the 2000-2001 season, immunization rates
      at 7 hospitals and among HCWs in high-risk units exceeded the National
      Association of Children's Hospitals and Related Institutions goal of 50%.

PMID- 15566024
TI  - Use of a mobile cart influenza program for vaccination of hospital employees.
AB  - OBJECTIVE: Rates of annual influenza vaccination of healthcare workers (HCWs)
      remained low in our university hospital. This study was conducted to evaluate the
      impact of a mobile cart influenza vaccination program on HCW vaccination.
      METHODS: From 2000 to 2002, the employee health service continued its annual
      influenza vaccination program and the mobile cart program was implemented
      throughout the institution. This program offered influenza vaccination to all
      employees directly on the units. Each employee completed a questionnaire.
      Vaccination rates were analyzed using the Mantel-Haenszel test. RESULTS: The
      program proposed vaccination to 50% to 56% of the employees. Among the
      nonvaccinated employees, 52% to 53% agreed to be vaccinated. The compliance with
      vaccination varied from 61% to 77% among physicians and medical students and from
      38% to 55% among nurses and other employees. Vaccination of the chief or
      associate professor of the unit was associated with a higher vaccination rate of
      the medical staff (P < .01). Altogether, the vaccination program led to an
      increase in influenza vaccination among employees from 6% in 1998 and 7% in 1999
      before the mobile cart program to 32% in 2000, 35% in 2001, and 32% in 2002 (P <
      .001). CONCLUSIONS: The mobile cart program was associated with a significantly
      increased vaccination acceptance. Our study was able to identify HCW groups for
      which the mobile cart was effective and highlight the role of the unit head in
      its success.

PMID- 15566025
TI  - Preventing nosocomial influenza by improving the vaccine acceptance rate of
      clinicians.
AB  - OBJECTIVES: To assess the effects of interventions to prevent transmission of
      influenza and to increase employee compliance with influenza vaccination. DESIGN:
      The change in the proportion of hospitalized patients with laboratory-confirmed
      nosocomial influenza was observed over time and assessed using chi-square for
      trend analysis. The association between nosocomial influenza in patients and
      healthcare worker (HCW) compliance with vaccine was assessed by logistic
      regression. SETTING: A 600-bed, tertiary-care academic hospital. METHODS: After
      an outbreak of influenza A at this hospital in 1988, a mobile cart program was
      instituted with increased efforts to motivate employees to be vaccinated and
      furloughed when ill as well as new measures to prevent nosocomial spread.
      RESULTS: HCW vaccination rates increased from 4% in 1987-1988 to 67% in 1999-2000
      (P < .0001). Proportions of nosocomially acquired influenza cases among employees
      or patients both declined significantly (P < .0001). Logistic regression analysis
      revealed a significant inverse association between HCW compliance with
      vaccination and the rate of nosocomial influenza among patients (P < .001).
      CONCLUSION: A mobile cart vaccination program and an increased emphasis on HCWs
      to receive the vaccine were associated with a significant increase in vaccine
      acceptance and a significant decrease in the rate of nosocomial influenza among
      patients.

PMID- 15566026
TI  - Influenza vaccination: a collaborative effort to improve the health of the
      community.
AB  - BACKGROUND: The need to improve influenza vaccination delivery in our community
      became painfully clear during the winter of 1997-1998 when high rates of
      respiratory illness led to congestion in the emergency department and a critical
      shortage of hospital beds. In response, the local hospital and the Department of
      Health launched a collaborative program to increase influenza vaccine coverage in
      the community. METHODS: The partnership was designed to increase the number of
      citizens receiving influenza vaccine and to moderate the severity of lower
      respiratory tract illness during the winter season. A variety of methods were
      used to increase public awareness, enhance vaccine delivery, and create a
      relatively seamless service for the community. RESULTS: During three seasons,
      influenza vaccination rates increased by a relative 150%. This represented
      immunization of 16% of the entire community and more than 75% of residents older
      than 65 years. Hospital employee vaccination rates also rose from 34% to 58%.
      When compared with other hospitals in the county, the campaign reduced the
      average number of annual visits to the emergency department for all respiratory
      diagnoses by 34% and exacerbations of chronic obstructive pulmonary disease by
      46%. CONCLUSIONS: This influenza vaccination program illustrates the potential
      for synergy that exists between local departments of health and community
      hospitals in successfully increasing vaccine delivery to the community.
      Furthermore, it also suggests that such efforts can be successful in reducing use
      of the emergency department, resulting in a positive impact on the health of the
      community.

PMID- 15566027
TI  - Attitudes and practices regarding influenza vaccination among healthcare workers
      providing services to individuals with spinal cord injuries and disorders.
AB  - OBJECTIVE: To examine influenza vaccination status and predictors for vaccine
      receipt among healthcare workers (HCWs) caring for patients with spinal cord
      injuries and disorders. DESIGN: Cross-sectional, nationwide anonymous survey.
      SETTING: Twenty-three Veterans Affairs spinal cord injury centers. PARTICIPANTS:
      One thousand five hundred fifty-six HCWs. METHODS: The primary outcome was staff
      vaccination status. Independent variables included staff demographic and
      employment characteristics, health status, attitudes and beliefs about the
      vaccine, and implications for its use. RESULTS: The staff vaccination rate was
      51%. Leading motivators of vaccine receipt were self-protection (77%) and patient
      protection (49%). The most common reasons for nonreceipt were concerns about side
      effects (49%), preventive quality (20%), and inconvenience (14%). Logistic
      regression results suggested that age of 50 years or older (OR, 1.47; P = .021),
      male gender (OR, 2.50; P < .001), strong belief in vaccine effectiveness (OR,
      19.03; P = .008), and importance of HCW vaccination (OR, 20.50; P = .005)
      significantly increased the probability of vaccination. Recommending the vaccine
      to coworkers, patients, or patients' families was also associated with HCW
      vaccination (OR, 3.20; P < .001). Providers who did not believe the vaccine was
      protective (P < .001) or effective (P < .001) were less likely to recommend it to
      patients. CONCLUSIONS: Strategies to increase vaccination rates among HCWs should
      address concerns about side effects, effectiveness, and protective value of the
      vaccine and access to it. The impact of provider recommendations should be
      stressed. Vaccination and subsequent prevention of illness may limit morbidity
      and mortality, thus benefiting HCWs, healthcare facilities, and patients.

PMID- 15566028
TI  - Work-site-based influenza vaccination in healthcare and non-healthcare settings.
AB  - OBJECTIVE: To better understand work-site-based programs for influenza
      vaccination. DESIGN: Self-administered, mailed questionnaire. SETTING: Healthcare
      and non-healthcare companies. PARTICIPANTS: Random sample of 2000 members of the
      American Association of Occupational Health Nurses. RESULTS: The response rate
      was 55%, and 88% of the respondents were employed by companies sponsoring work
      site influenza vaccination. Thirty-two percent of respondents worked for
      healthcare and healthcare-related services companies. Healthcare companies were
      more likely to sponsor worksite-based vaccination (94% vs 85%; P < .0001)
      compared with non-healthcare companies. Healthcare companies were also more
      likely to encourage vaccination of high-risk employees (70% vs 55%; P < .0001)
      and cover its cost (86% vs 61%; P < .0001). Multivariate logistic regression was
      used to determine factors associated with highly successful vaccination. Being a
      healthcare-related company (OR, 2.1; CI95, 1.4-3.2; P < .0001), employers
      covering the vaccination cost (OR, 3.1; CI95, 1.4-6.6; P = .004), having more
      experience with work-site vaccination (OR, 1.6; CI95, 1.0-2.4; P = .036), and
      management encouraging vaccination (OR, 2.6; CI95, 1.4-4.9; P = .002) were
      associated with highly successful programs. CONCLUSIONS: Most of the occupational
      health nurses surveyed work for employers sponsoring work-site vaccination, and
      32% were employed by healthcare and related services companies. Healthcare
      companies were more likely to sponsor worksite-based vaccination and to vaccinate
      most of their employees; however, only 18% had vaccination rates higher than 50%.
      Strategies need to be developed to increase vaccination rates so that benefits of
      vaccination can be realized by employers and employees.

PMID- 15566029
TI  - Characteristics of long-term-care facility residents associated with receipt of
      influenza and pneumococcal vaccinations.
AB  - BACKGROUND: Studies have found residency in long-term-care facilities (LTCFs) a
      risk factor for influenza and pneumonia and have demonstrated that vaccinations
      against these diseases reduce the risk of disease. However, rates are below
      Healthy People 2010 goals of 90% for LTCFs. During 1999-2002, a multi-state
      demonstration project was conducted in LTCFs to implement standing orders
      programs for immunizations. OBJECTIVE: Identify nursing home resident-specific
      characteristics associated with vaccination coverage at baseline. METHODS:
      Facility-level data were collected from self-reported surveys of selected nursing
      homes in 14 states and from the On-line Survey and Certification Reporting
      System. Resident-level data, including demographics and physical functioning,
      were obtained from the Centers for Medicare & Medicaid Services' Minimum Data
      Set; 2000-2001 vaccination status was obtained by chart review. Influenza
      vaccination status reflected a single season, whereas pneumococcal vaccination
      status reflected vaccination in the past. Multilevel analysis was used to control
      for facility-level variation. RESULTS: Of 22,188 residents sampled in 249 LTCFs,
      complete data were obtained for 20,516 (92%). The average coverage for
      immunizations was 58.5% +/- 0.7% for influenza and 34.6% +/- 0.3% for
      pneumococcal. On bivariate analyses, residents with cognitive, psychiatric, or
      neurologic problems were more likely to be vaccinated; those with accidental
      injuries, unstable conditions, or cancer were less likely to receive either
      vaccine. On multilevel analysis, the strongest resident characteristics
      associated with receipt of immunizations, controlling facility variation, were
      cognitive deficits and psychiatric illness. CONCLUSION: The variation in baseline
      vaccination coverage associated with LTCF resident characteristics supports the
      need for strategies to increase vaccination coverage in LTCFs.

PMID- 15566030
TI  - Adverse effects of amantadine and oseltamivir used during respiratory outbreaks
      in a center for developmentally disabled adults.
AB  - BACKGROUND AND OBJECTIVES: Antiviral prophylaxis is recommended for the control
      of institutional influenza A outbreaks. In long-term-care institutions other than
      nursing homes, neither the seriousness of influenza nor the risks and benefits of
      antiviral prophylaxis is clearly understood. We studied the severity of illness
      due to influenza among adults residing in a center for the developmentally
      disabled and assessed adverse reactions to amantadine and oseltamivir
      prophylaxis. METHODS: Data were collected from the charts of consenting
      residents. Complications of upper respiratory tract illness were recorded.
      Potential adverse events were documented during amantadine and oseltamivir
      therapy, and during a baseline period with neither medication. RESULTS: The
      median age of the 287 participants was 46.4 years. Only 15 (5%) were older than
      65 years, and 69 (24%) had chronic underlying medical illness placing them at
      high risk for influenza. Of the 122 residents with an upper respiratory tract
      infection, 16 (13%) developed pneumonia, 12 (9.8%) were hospitalized, and 5 (4%)
      died. Twenty-eight (25%) of 112 residents had an adverse neurologic event while
      receiving amantadine prophylaxis, compared with 3 (2.7%) receiving no antiviral
      medication and 5 (4.5%) receiving oseltamivir (P < .001). Sixteen percent of the
      residents discontinued amantadine due to adverse events; in contrast, adverse
      events were identified in 2.9% of the residents prescribed oseltamivir, and none
      discontinued therapy. CONCLUSIONS: Viral respiratory tract infections are
      associated with a high risk of complications in this population. The rate of
      adverse neurologic events associated with amantadine was significantly higher
      than that associated with oseltamivir.

PMID- 15566031
TI  - Concurrent summer influenza and pertussis outbreaks in a nursing home in Sydney,
      Australia.
AB  - OBJECTIVE: To report on the investigation of a summer outbreak of acute
      respiratory illness among residents of a Sydney nursing home. DESIGN: An
      epidemiologic and microbiological investigation of the resident cohort at the
      time of the outbreak and medical record review 5 months later. SETTING: A nursing
      home located in Sydney, Australia, during February to July 1999. PATIENTS: The
      cohort of residents present in the nursing home at the time of the outbreak.
      INTERVENTIONS: Public health interventions included recommendations regarding
      hygiene, cohorting of residents and staff, closure to further admissions, and
      prompt reporting of illness; and virologic and serologic studies of residents.
      RESULTS: Of the 69 residents (mean age, 85.1 years), 35 fulfilled the case
      definition of acute respiratory illness. Influenza A infection was confirmed in
      19 residents, and phylogenetic analysis of the resulting isolate, designated H3N2
      A/Sydney/203/99, showed that it differed from strains isolated in eastern
      Australia during the same period. Serologic evidence of Bordetella infection was
      also found in 10 residents; however, stratified epidemiologic analysis pointed to
      influenza A as the cause of illness. CONCLUSIONS: The investigation revealed an
      unusual summer outbreak of influenza A concurrent with subclinical pertussis
      infection. Surveillance of acute respiratory illness in nursing homes throughout
      the year, rather than solely during epidemic periods, in combination with
      appropriate public health laboratory support, would allow initiation of a timely
      public health response to outbreaks of acute respiratory illness in this setting.

PMID- 15566032
TI  - Surveillance for transmission and antibiotic adverse events among neonates and
      adults exposed to a healthcare worker with pertussis.
AB  - BACKGROUND: During a hospital obstetric rotation, a medical student demonstrated
      classic symptoms of pertussis. The diagnosis was confirmed by isolation of
      Bordetella pertussis. Because this exposure occurred in a high-risk hospital
      setting, control measures were undertaken to prevent transmission and illness.
      OBJECTIVES: To identify secondary cases of pertussis, to determine compliance
      with chemoprophylaxis recommendations, and to monitor for adverse events
      associated with chemoprophylaxis following a hospital exposure to pertussis.
      PATIENTS: More than 500 individuals were potentially exposed, including 168
      neonates; antimicrobial chemoprophylaxis was administered to 281 individuals.
      Fifty-eight neonates and 194 adults began azithromycin chemoprophylaxis; 18
      neonates and 2 adults began erythromycin chemoprophylaxis. METHODS: Active
      surveillance was instituted for (1) secondary cases of pertussis among healthcare
      coworkers, obstetric patients, their neonates, and labor companions and (2)
      antibiotic compliance and tolerance. RESULTS: No secondary cases of pertussis
      were confirmed by laboratory tests; however, 26 suspected cases and 5 clinically
      compatible cases were identified. Antibiotic courses were completed by 95% of the
      individuals who initiated therapy. Neonates taking azithromycin had statistically
      significantly less gastrointestinal distress compared with neonates taking
      erythromycin (12% vs 50%; P = .002); there were no cases of infantile
      hypertrophic pyloric stenosis. CONCLUSIONS: Although it was not possible to
      assess the effectiveness of the antibiotic regimens, the lack of laboratory
      confirmed secondary cases suggests control measures were successful. Data from
      the 58 neonates who received azithromycin suggest it may be well tolerated in
      this age group.

PMID- 15566033
TI  - Catheter-associated urinary tract infections in intensive care units can be
      reduced by prompting physicians to remove unnecessary catheters.
AB  - OBJECTIVE: Indwelling urinary catheters are the most common source of infections
      in intensive care units (ICUs). The aim of this study was to evaluate the
      efficacy of nurse-generated daily reminders to physicians to remove unnecessary
      urinary catheters 5 days after insertion. DESIGN: A time-sequence nonrandomized
      intervention study. SETTING: Adult ICUs (medical, surgical, cardiovascular
      surgical, neurosurgical, and coronary care) of a tertiary-care university medical
      center. PATIENTS: All patients admitted to the adult ICUs during a 2-year period.
      The study consisted of a 12-month observational phase (15,960 patient-days)
      followed by a 12-month intervention phase (15,525 patient-days). INTERVENTION:
      Daily reminders to physicians from the nursing staff to remove unnecessary
      urinary catheters 5 days after insertion. RESULTS: The duration of urinary
      catheterization was significantly reduced during the intervention phase (from 7.0
      + 1.1 days to 4.6 +/- 0.7 days; P < .001). The rate of catheter-associated
      urinary tract infection (CAUTI) was also significantly reduced (from 11.5 +/- 3.1
      to 8.3 +/- 2.5 patients with CAUTI per 1,000 catheter-days; P = .009). There was
      a linear relationship between the monthly average duration of catheterization and
      the rate of CAUTI (r = 0.50; P = .01). The excess monthly cost of antibiotics for
      CAUTI was reduced by 69% (from 4021 dollars +/- 1800 dollars to 1220 dollars +/-
      941 dollars; P = .004). CONCLUSION: This study demonstrated that a simple measure
      instituted as part of a continuous quality improvement program significantly
      reduced the duration of urinary catheterization, rate of CAUTI, and additional
      costs of antibiotics to manage CAUTI.

PMID- 15566034
TI  - Cockroaches as potential vectors of nosocomial infections.
AB  - OBJECTIVE: To determine the possible role of cockroaches in the epidemiology of
      nosocomial infections. DESIGN: Epidemiologic investigation of bacteria and fungi
      in cockroaches and evaluation of the antibiotic resistance of the bacteria
      isolated from the insects. SETTING: Ninety hospitals in Kaohsiung City and
      Kaohsiung County in Taiwan. METHODS: Cockroaches were collected in clinical and
      nonclinical areas and microorganisms were isolated from their external surface
      and alimentary tract. The susceptibilities of Staphylococcus aureus, Enterococcus
      species, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli,
      Serratia marcescens, and Proteus species to 17 antibiotics were tested. RESULTS:
      Cockroach infestation was found in 46.7% of the hospitals studied. Two hundred
      three cockroaches were collected (139 Periplaneta americana and 64 Blattella
      germanica). Periplaneta americana was found more often in nonclinical areas
      (64.5%) and B. germanica in clinical areas (78.1%). There was no statistically
      significant difference between Periplaneta americana (98.6%) and B. germanica
      (96.9%) regarding overall isolation rate (P > .05). However, 33 species of
      bacteria and 16 species of fungi were isolated from Periplaneta americana and
      only 23 and 12, respectively, from B. germanica. Resistance to ampicillin (13.7%
      to 100%), chloramphenicol (14.3% to 71.4%), tetracycline (14.3% to 73.3%), and
      trimethoprim-sulfamethoxazole (14.3% to 57.1%) was found in two gram-positive and
      five gram-negative bacteria. CONCLUSION: Because cockroach infestation occurred
      in more than 40% of the hospitals and nearly all of the cockroaches harbored
      bacteria with multidrug resistance and fungi, cockroaches may play a potential
      role in the epidemiology of nosocomial infections in those hospitals.

PMID- 15566035
TI  - Pneumococcal immunization in older adults: implications for the long-term-care
      setting.
AB  - OBJECTIVES: To compare the efficacy of the polysaccharide pneumococcal vaccine in
      older adults between clinical trial and observational studies and to discuss the
      implications for long-term-care facilities (LTCFs). DATA SOURCE: A Medline search
      (to April 2003). STUDY SELECTION: All meta-analyses of randomized and quasi
      randomized trials of pneumococcal vaccines with placebo or no treatment were
      sought. All cohort or case-control studies were sought. DATA SYNTHESIS: Of the 16
      individual randomized clinical trials included in the reviews, 8 compared
      pneumococcal vaccine in individuals 55 years and older individuals. Only one
      study specifically addressed LTCF residents. Although no significant protective
      effect of the vaccine in elderly subpopulations was found, on the basis of wide
      confidence intervals and small subpopulation sample sizes, beneficial effects,
      particularly for pneumococcal bacteremia, could not be ruled out. Of the
      individual observational studies, 11 specifically evaluated vaccine efficacy in
      older adults. Vaccine efficacy was demonstrated in 9 of the 11 studies with no
      protective effect was shown in 2 studies. CONCLUSION: Although the pooling of
      clinical trial data does not demonstrate significant efficacy of the pneumococcal
      polysaccharide vaccine in subgroups of older adults, these subgroup studies
      lacked power to show significant differences. Observational studies repeatedly
      demonstrate efficacy in older adults, and the vaccine has been demonstrated to be
      cost-effective and safe. It is strongly promoted by U.S. and Canadian advisory
      committees. On the basis of this available evidence, the pneumococcal
      polysaccharide vaccine should currently be recommended for older adults,
      especially those who are residents of LTCFs.

PMID- 15566036
TI  - Nosocomial pertussis outbreak among adult patients and healthcare workers.
AB  - We describe a pertussis outbreak among adult patients in a French general
      hospital following transmission from a healthcare worker. This index case
      transmitted pertussis to other healthcare workers, who, in turn, contaminated
      other staff and two immunosuppressed patients. This raises questions about
      infection control.

PMID- 15566037
TI  - Should electronic faucets be recommended in hospitals?
AB  - Microbiological examinations of electronic faucets newly installed in a hospital
      kitchen revealed high bacteria counts and Pseudomonas aeruginosa during a 6-month
      period of observation. Our data suggest that the use of electronic faucets poses
      a potential risk for nosocomial infection in high-risk areas of hospitals.

PMID- 15566038
TI  - Colonization of personal digital assistants carried by healthcare professionals.
AB  - This study evaluated personal digital assistant (PDA) microbial colonization
      before and after cleaning with alcohol. Samples from 75 PDAs were processed.
      Before cleaning, 96% of the samples were culture positive. After cleaning, 75%
      became culture negative. PDAs cleaned with an alcohol swab demonstrated
      significant reduction in colonization.

PMID- 15566039
TI  - Persistent Acinetobacter baumannii? Look inside your medical equipment.
AB  - Two outbreaks of multidrug-resistant Acinetobacter baumannii occurred in our
      hospital. The outbreak strains were eventually isolated from respiratory
      ventilators, an apparatus used to cool or warm patients, and four continuous veno
      venous hemofiltration machines. Removing dust from the machines and replacing all
      dust filters brought the outbreaks to an end.

PMID- 15566040
TI  - Epidemiologic study of nosocomial urinary tract infections in Saudi military
      hospitals.
AB  - A case-control study of patients with and without confirmed UTI was performed to
      identify risk factors for nosocomial UTI. Duration of hospitalization, unit of
      admission, history of diabetes mellitus or debilitating diseases, and duration
      and number of urinary catheters were independently associated with increased risk
      of nosocomial UTIs.

PMID- 15566041
TI  - Accessibility of electronically mediated education: policy issues.
AB  - Electronic technology has transformed education systems over the past 30 years.
      Generally speaking, technology has been an incredible benefit for individuals
      with disabilities. However, the use of technology, particularly in education, has
      been sometimes discriminatory toward those who are unable to interact with it in
      the standard ways anticipated by its inventors. Disability policies have
      attempted to address issues of equality of opportunity for all citizens, but
      application of these policies to rapidly evolving technology has been difficult.
      In this article we provide a brief review of disability policy as it pertains to
      education. We also review several current policy initiatives related to higher
      education information technology--all of which pertain to public kindergarten
      through 12th-grade education. We raise questions that arise when careful thought
      is given to ways in which disability, education, and technology policies overlap.
      We anticipate that these next few pages will generate dialogue among researchers,
      policy makers, educators, technology engineers, and others interested in how
      electronically mediated education affects individuals with disabilities and how
      it can be used to ensure equal access to the educational benefits available in
      schools protected by U.S. civil rights legislation.

PMID- 15566042
TI  - Factors that motivate and deter rehabilitation educators from participating in
      distance education.
AB  - The major purpose of the study was to conduct exploratory research on the
      motivational levels of rehabilitation educators whose programs have Comprehensive
      Service Personnel Development (CSPD; Department of Education grant) grants
      targeted toward distance education. Additionally, the study attempted to identify
      whether significant factors existed that would inhibit faculty participation in
      distance education. There were three research questions to examine: (a) Do
      distance educators and non-distance educators differ significantly in intrinsic
      motivational factors? (b) Do distance educators and non-distance educators differ
      significantly in extrinsic motivational factors? and (c) Do distance educators
      and non-distance educators differ significantly in inhibiting factors? The
      results showed that rehabilitation faculty with CSPD grants who are distance
      educators are more extrinsically motivated (such as increase in salary, monetary
      support for participation, job security, working conditions, technical support,
      and requirement by department) than non-distance educators. There were no
      significant differences in levels between distance educators and non-distance
      educators that are intrinsically motivated (scholarly pursuit, personal research
      tool, and job satisfaction). There was no significant difference between distance
      educators and non-distance educators in inhibiting factors.

PMID- 15566043
TI  - Rehabilitation professionals' satisfaction with continuing education delivered at
      a distance using different technologies.
AB  - This paper examines learner satisfaction with technologies used for distance
      delivery of continuing education across 10 Canadian sites: nine within the
      province of Alberta and one in Nunavut Territory. The technologies were satellite
      (or videotapes of) broadcasts, videoconferencing, and web-based technology.
      Learner satisfaction was evaluated using questionnaires. A survey on general
      issues related to continuing education was developed and mailed to random samples
      of health professionals and a convenience sample of stakeholders. The learners (n
      = 1,141) represented 20 types of health service providers who had attended at
      least one session delivered via satellite, videotape, or videoconferencing. Seven
      individuals completed the web-based course. Overall, the majority of participants
      were satisfied or very satisfied. In general, satellite delivery was received
      more favorably compared with videotapes of the same content. A total of 350 (33%
      response rate) health professionals and 37 (50% response rate) stakeholders
      returned the surveys. Nearly 50% of health professionals thought that clinical
      case presentations (rounds) were valuable to them, but over half of the
      stakeholders perceived that videotapes, rounds, and research seminars were
      valuable to health professionals. Ratings for the web-based course varied,
      indicating different learner characteristics. We conclude that it is possible to
      utilize multiple technologies to meet the continuing education needs of an
      interdisciplinary group of health service providers, but future research is
      needed to develop a framework for evaluating the usability of multiple existing
      and emerging technologies for distance education.

PMID- 15566044
TI  - Making distance education accessible for students who are deaf and hard-of
      hearing.
AB  - Distance education is based on providing learning "anytime, anywhere." The design
      of many distance education courses, however, may actually erect barriers to the
      full participation of some students with disabilities, particularly those with
      hearing impairments. Without careful consideration, distance education could
      become learning anytime, anywhere, but not for anybody. It is not only unethical,
      but also illegal to ignore the special needs of these learners. The specific
      impact of such legislation on distance education for those students with hearing
      impairments will be addressed. Students with disabilities are often faced with a
      double digital divide that must be bridged. Universal design uses an excellent
      proactive approach to closing this digital divide caused by inaccessible courses.
      Each medium of transmission in distance education poses unique access barriers.
      Even within the same medium, what is best for one student or class may not be the
      most ideal accommodation in another situation. Individualized accommodation
      methods will be examined, and specific technologies and software will be
      discussed.

PMID- 15566045
TI  - Speeding up learning: accelerated distance learning in rehabilitation education.
AB  - Distance learning in higher education involves a continum of technologies ranging
      from teleconferencing to video streaming. The United States is approaching a
      crisis in personnel shortages in rehabilitation counseling and education. Because
      of these shortages, higher education is called upon to produce counselors in an
      abbreviated period of time. Thus, distance learning is recognized as an integral
      part of education, especially for adult learners. This article provides an
      overview and discussion of the relevance of distance and accelerated learning in
      rehabilitation and higher education.

PMID- 15566046
TI  - Leveling the playing field: the development of a distance education program in
      rehabilitation counseling.
AB  - This article describes the curriculum design and development of an online
      Master's degree program in Rehabilitation Counseling at the University of South
      Carolina. The use of Bloom's Taxonomy as a method for selecting distance
      education techniques and teaching methods to ensure equivalency of the
      educational experience to traditional classroom teaching is described. The author
      presents tables to demonstrate the cognitive competencies, traditional and
      distance education methods, and use of synchronous and asynchronous methods in
      reaching desired educational objectives. This process has resulted in the
      creation of a program that offers distance education options, traditional
      classroom options, or a blend of approaches. The menu of options has met the
      unique learning needs of all students and has offered students with disabilities
      a level playing field on which to build rehabilitation counseling competencies.

PMID- 15566047
TI  - Community variation in risk and protective factors and substance use outcomes.
AB  - Communities are the context in which many prevention activities take place. One
      approach to community prevention is to identify the most elevated risk factors
      and most depressed protective factors for substance use in a community and then
      to select and implement preventive interventions to address the most elevated
      risk factors and most depressed protective factors in the community. This
      approach presumes that there are reliable differences between communities in risk
      and protection and that these differences relate to differences in substance use
      across communities. This paper addresses these issues using data from 28,091
      students in 41 communities across the U.S. Intraclass correlation coefficients
      are used to assess the degree to which there are reliable and meaningful
      differences between communities in levels of risk and protective factors. The
      community means of the risk and protective factors are then correlated with
      levels of substance use. Findings indicate that there are meaningful differences
      between communities in levels of specific risk and protective factors, and that
      those differences are related to different levels of substance use in these
      communities. These results provide an empirical foundation for tailoring
      community-wide efforts to prevent substance abuse to the specific profiles of
      risk and protective factors experienced by youths in different communities.

PMID- 15566048
TI  - Can I have a beer, please? A study of alcohol service to young adults on licensed
      premises in Stockholm.
AB  - This study evaluated the effects of a community alcohol prevention program on the
      frequency of alcohol service to young adults at licensed premises in Stockholm,
      Sweden. We used a pretest (1996)-posttests (1998 and 2001) design with
      intervention and control areas. The multicomponent intervention combines training
      of serving staff in responsible beverage service, policy initiatives, and
      enforcement of existing alcohol regulations. Adolescents 18 years old (the legal
      drinking age on licensed premises in Sweden), but younger looking according to an
      expert panel, visited licensed premises in pairs, where each adolescent ordered a
      beer. At baseline in 1996, the adolescents made 600 attempts to order. At follow
      up in 1998, the number of attempts to order was 252, and at the second follow-up
      in 2001, the adolescents made 238 attempts. We found no statistically significant
      differences between the intervention and control areas. Overall, the frequency of
      alcohol service to adolescents on licensed premises in these areas of Stockholm
      decreased significantly over time, from 45 to 41 and to 32%, in 1996, 1998, and
      2001, respectively. The decrease in alcohol service in 2001 was statistically
      significant compared to the baseline in 1996. One explanation for this
      improvement could be more effective enforcement of existing alcohol laws in both
      the intervention and control areas. We also found that licensed premises that
      used doormen to screen potential customers were less likely to sell to minors.

PMID- 15566049
TI  - Attitudes and dating aggression: a cognitive dissonance approach.
AB  - This study examined the association between attitudes about dating aggression and
      select dating aggressive behaviors (verbal aggression and jealous behavior) in
      high school students. Our hypothesis, derived from cognitive dissonance theory,
      was that discrepancies between self-reported attitudes and aggressive behavior at
      Time 1 (i.e., putative cognitive dissonance) would predict decreases in
      aggression between Time 1 and Time 2 beyond what would be predicted by change in
      attitudes over the same period. Results indicated that cognitive dissonance (as
      indexed by the discrepancy between attitudes and behavior) was generally a
      significant predictor of behavior change, providing significant improvement in
      prediction of behavior over attitude change alone. We discuss the implications of
      these findings for prevention efforts and directions for future research in this
      area.

PMID- 15566050
TI  - How early experience matters in intellectual development in the case of poverty.
AB  - Experiments with rodents indicate that severe early psychological and social
      deprivation has lasting detrimental effects on learning ability that are not
      remedied by exposure to enriching experiences in adulthood. Findings indicate
      that environmental adversity early in life works to limit the development of
      intelligence with consequences for later functioning. Animal experiments are best
      viewed as supplying a rationale for early intervention in disadvantaged infants
      and children who would otherwise be likely to evince low intellectual
      capabilities later in life. Animal experiments conducted to date do not support
      an interpretation that early enrichment necessarily boosts later intellectual
      performance beyond the normal or species-typical range. They indicate that early
      intervention promotes normative development by preventing adverse early rearing
      conditions from leading to negative consequences for cognitive ability and self
      regulation. The Abecedarian Project, an early enrichment intervention with
      infants from economically deprived backgrounds, is presented as an example of how
      early experience matters in terms of human intellectual development in
      disadvantaged populations. The results of that program reflect what one would
      expect from the rodent studies mentioned above.

PMID- 15566051
TI  - Do after school programs reduce delinquency?
AB  - After school programs (ASPs) are popular and receive substantial public funding.
      Aside from their child-care and supervision value, ASPs often provide youth
      development and skill-building activities that might reduce delinquent behavior.
      These possibilities and the observation that arrests for juvenile crime peak
      between 2 p.m. and 6 p.m. on school days have increased interest in the
      delinquency prevention potential of ASPs. This study examined effects of
      participation in ASPs conducted in Maryland during the 1999--2000 school year and
      the mechanism through which such programs may affect delinquent behavior. Results
      imply that participation reduced delinquent behavior for middle-school but not
      for elementary-school-aged youths. This reduction was not achieved by decreasing
      time spent unsupervised or by increasing involvement in constructive activities,
      but by increasing intentions not to use drugs and positive peer associations.
      Effects on these outcomes were strongest in programs that incorporated a high
      emphasis on social skills and character development.

PMID- 15566052
TI  - Tobacco and alcohol use as an explanation for the association between
      externalizing behavior and illicit drug use among delinquent adolescents.
AB  - The prevalence and persistence of adolescent substance use and abuse is a
      national health issue, and substance use among adolescents is frequently comorbid
      with other psychiatric disorders. Most studies in this area utilize samples of
      middle or high school students or from inpatient settings. Less is known about
      substance use and psychiatric comorbidity among delinquent adolescents. The
      present study examined data from two cohorts of juvenile offenders collected over
      a 2-year period (n = 245, n = 299). Participants reported frequency of cigarette,
      alcohol, marijuana, and other substance use. Participants' parents completed a
      measure of behavior problems. Path analyses suggested that parental reports of
      externalizing problems were significantly related to self-reported substance use
      while parental reports of internalizing problems were not. Results also suggested
      that smoking and alcohol use act as mediators between externalizing problems and
      marijuana and other drug use. Although there were some mean differences by
      gender, the pattern of relationships amongst the variables did not differ by
      gender. Implications of the findings and future directions are discussed.

PMID- 15566053
TI  - Suicide: causes and prevention.

PMID- 15566054
TI  - Diabetes and the heart.

PMID- 15566055
TI  - The unstable shoulder.
AB  - Not all unstable shoulders are the same, and careful patient selection ensures
      proper treatment. Improved understanding of the mechanisms of stability, advances
      in imaging and arthroscopic technology mean that repeated visits to the emergency
      department with a painful dislocated shoulder should be a thing of the past.

PMID- 15566056
TI  - Shoulder pain in sports.
AB  - Shoulder pain in athletic individuals is common, particularly in those sports
      that are upper limb dominant. It is important to make an accurate diagnosis so
      that appropriate treatment can be directed at the cause.

PMID- 15566057
TI  - Ectopic pregnancy deaths: what should we be doing?
AB  - Ectopic pregnancy is the leading cause of maternal mortality in the first
      trimester of pregnancy. A greater awareness of risk factors and improved
      diagnostic techniques now allow ectopic pregnancies to be identified before the
      development of life-threatening events. Non-surgical management options also
      decrease maternal morbidity.

PMID- 15566058
TI  - Developing maternity services in Scotland.
AB  - Close scrutiny of the maternity services in Scotland has been necessary because
      of the falling birth rate, the European working time directive, the
      geographically diverse population and the public expectation of good quality
      care. This article describes how this is being done.

PMID- 15566059
TI  - Melanoma vaccines.
AB  - Melanoma vaccines offer new hope to patients with metastatic melanoma, although
      convincing survival advantages have yet to be reported. This review outlines the
      progress made in this exciting field of research and looks ahead to the future.

PMID- 15566060
TI  - Medical management of severe traumatic brain injury.
AB  - This article reviews the current guidelines for the management of patients with
      severe traumatic brain injury from presentation in the accident and emergency
      department, through transfer, to specialist treatment in a neurocritical care
      unit.

PMID- 15566061
TI  - Anatomy: the future teaching of undergraduates.
AB  - The time devoted to the teaching of anatomy to medical students has long been
      under pressure. Much work has been devoted to how best to teach anatomy in both a
      time-efficient and cost-effective manner. This article discusses the main methods
      of teaching anatomy and their respective advantages and disadvantages as
      evidenced in the literature. Suggestions are made as to how best to teach anatomy
      to medical students in the future.

PMID- 15566062
TI  - Paediatric acute abdomen.

PMID- 15566063
TI  - Cerebellar arteriovenous malformation presenting with bilateral proptosis
      mimicking caroticocavernous fistula.

PMID- 15566064
TI  - Temporal arteritis in the absence of headache.

PMID- 15566065
TI  - Ocular symptoms and signs as presenting features of endocarditis caused by
      Streptococcus bovis II.

PMID- 15566066
TI  - Paronychia or an abscess: early diagnosis.

PMID- 15566067
TI  - Patient-held ECG: a flexible friend.

PMID- 15566068
TI  - To do or defer: a case with adult congenital heart disease.

PMID- 15566069
TI  - [Cytogenetic exploration of fetal ultrasound anomalies].
AB  - AIMS: To evaluate the rate of trisomies and other chromosome abnormalities after
      positive ultrasound findings in first and second trimester. METHODS: In this
      study authors investigate the chromosome abnormalities detected in cases with
      prior abnormal ultrasound findings. During a ten-year period there were 1907
      invasive interventions carried out with the purpose of chromosome analysis. The
      invasive intervention was genetic amniocentesis in 1619 cases and chorion villus
      sampling in 288 cases. RESULTS: Karyotyping revealed 103 cases (5.4%) with
      chromosome abnormalities. Abnormalities with subcutaneous oedema were examined:
      abnormal karyotype was found in 20% of cases with non-immune hydrops, 48.1% of
      cases with cystic hygroma, and 53.8% of cases with non-immune hydrops and cystic
      hygroma altogether, 8.3% of cases with nuchal oedema in the 1st trimester, and
      5.5% in the 2nd trimester. The incidence rate of chromosome abnormalities in
      cases with cerebral anomalies was 6.3% of cases with ventricular dilatation, 3.6%
      of cases with choroid plexus cysts, and 15.9% of cases with other cranial
      anomalies. Regarding abnormalities of the heart; isolated echogenic intracardiac
      focus and ventricular septal defects were not associated with chromosome
      abnormality, but, in conjunction with other positive ultrasound findings the
      incidence rate of chromosome abnormalities were 7.9% and 26.7%, respectively.
      Other anomalies of the heart and large blood vessels showed an abnormal karyotype
      incidence rate of 18.2%. In cases of unilateral pyelectasis unassociated with
      other anomalies, the incidence rate of the chromosome abnormalities was 1%. In
      cases of bilateral pyelectasis, or pyelectasis associated with other anomalies,
      the incidence rate was 3%. In terms of anomalies of the abdominal wall and the
      abdomen; the incidence rate of association with chromosome abnormalities was 9.5%
      in cases with omphalocele, 11.8% in cases with duodenal atresia, and 5.7% in
      cases with echogenic bowel. In cases with short femur and humerus the rate of
      abnormal karyotype was 16%. CONCLUSIONS: Ultrasound plays important role in
      prenatal screening and diagnostics. In cases with positive ultrasound findings,
      the performance of karyotyping is reasonable.

PMID- 15566070
TI  - [Data of the morbidity and mortality index of the acute coronary syndrome in the
      South Trans-Danubian Region between 1999 and 2002].
AB  - Data of the morbidity and mortality index of the acute coronary heart disease in
      the South Trans-Danubian Region between 1999 and 2002. South Trans-Danubian
      Regional Acute Coronary Registry. Based on GYOGYINFOK database, the authors'
      purpose was to monitor the morbidity and mortality of acute coronary heart
      diseases (acute coronary syndrome, acute myocardial infarction) in the
      approximately one million people inhabiting the South Trans Danubian Region. Data
      were obtained using the financing data sheets reported to GYOGYINFOK by 15 in
      patient health care institutions located in the region. The regional data were
      compared nation-wide ones as well. The observed diagnoses correspond to diseases
      the codes of which range from I 20.00 to I 22.90, according to BNO
      classification. The data of years 1999, 2000, 2001 and 2002 have already been
      processed and categorized by gender and age-groups. Hospital mortality,
      therapeutical procedures (thrombolysis, GP IIb/IIIa receptor blocker) as well as
      the parameters of progressive care have all been evaluated. Of the processed 4
      years, the data of 8431 patients are already recorded in the registry. The rate
      of the thrombolytic therapy reached patients was decreased from 26.01% (which was
      detailed in 1999) to 7.39% into 2002 in our region, but the rate was nearly
      constant 16.1% in 1999 and 13.28% in 2002 in the country. The rate of the GP
      IIb/IIIa therapy reached patients was increased from 2.15% to 6.66% in our
      region, while it was increased from 0.66% to 3.96% between 2000 and 2002 in the
      country. Mortality in the hospitals decreased in the case of male from 14.44% to
      8.7% in the region, and from 20.28% to 16.18% in the female. At the same time the
      hospital mortality was constant in the country, in males it was 14.39% in 1999,
      and 13.11% in 2002, and in females it was 20.00% in 1999, and 18.81 in 2002. As
      regards the therapeutical procedures--based on the data processed up to the
      present--it can be observed that classic thrombolytic therapy becomes de
      emphasized while treatments with GP IIb/IIIa receptor blockers as well as the
      intervention coupled to these gain ground. The authors consider the creation of
      this registry a very important beginning step in building the cardiological map
      of the region.

PMID- 15566071
TI  - [The effect of Helicobacter pylori eradication on prokinetic treatment on the
      quality of life in functional dyspepsia].
AB  - INTRODUCTION: The quality life is impaired in functional dyspepsia. Little is
      known, however, about the impact of different therapies on the quality of life in
      this condition. AIM OF STUDY: The scope of this study is to detect the change
      over time of the quality of life under two different treatments in functional
      dyspepsia. METHODS: One-hundred-one Helicobacter pylori positive and 98
      Helicobacter pylori negative functional dyspepsia patients have been enrolled in
      a prospective, controlled study. Organic digestive diseases were excluded by
      endoscopy and abdominal ultrasound. The quality of life was assessed by a disease
      specific questionnaire developed by the MAPI Research Institute, Lyon, France,
      translated and validated in Hungarian. Helicobacter pylori positive patients
      received one week triple regimen consisting in 2 x 40 mg pantoprazole + 2 x 1000
      mg amoxicillin + 2 x 500 mg clarithromycin followed by on-demand ranitidine (1-2
      x 150 mg) during 1 year of follow-up. Control 13C-urea breath test was performed
      6 weeks after eradication. Helicobacter pylori negative patients received 3 x 10
      mg cisapride for 6 weeks followed by on-demand prokinetic for 1 year. The
      questionnaire was self-administered at baseline, after 6 weeks and 1 year.
      RESULTS: The eradication rate of Helicobacter pylori was of 76.4% on an
      'intention-to treat' and 82.6% on 'per protocol' analysis. In patients with
      successful eradication, the standardized and transformed quality of life score
      increased after 6-8 weeks from 56.2 + 9.8 (95% confidence interval: 53.9-58.4) to
      70.8 + 10.7 (68.3-73.5) (p = 0.0001) and to 75.3 + 9.3 (73.2-77.5) at 1 year (p =
      0.005). In the patients with failed eradication, the quality of life has not been
      changed significantly (p = 0.76). The quality of life scores increased in
      Helicobacter pylori negative cases from 60.0 + 9.8 (58.0-62.0) to 73.3 + 9.6
      (71.3 + 75.4) after 6 weeks (p = 0.0001) and to 76.5 + 8.5 (74.5 - 78.4) at 1
      year (p = 0.56). The effect size was large in both groups and there were no
      differences between the treatment arms either at 6-8 weeks (p = 0.11) or after 1
      year (p = 0.43). CONCLUSIONS: Eradication of Helicobacter pylori infection and
      prokinetic treatment lead to significant improvement of the quality of life in
      functional dyspepsia. The disease-specific questionnaire was sensitive enough to
      capture the changes over time induced by the given therapies.

PMID- 15566072
TI  - [Wilson disease].
AB  - Wilson disease is an autosomal, recessive inherited disorder of copper
      metabolism, characterized by the accumulation of copper in the body due to
      defective biliary copper excretion of hepatocytes. Recently, novel components
      involved in copper metabolism, Wilson disease protein (ATP7B) and copper
      chaperones, have been identified. It has been demonstrated that ATP7B functions
      in copper secretion into the plasma, coupled with coeruloplasmin synthesis and
      biliary copper excretion. Genetic testing may help early diagnosis and with the
      beginning of therapy the development of symptoms can be prevented. Various
      mutations of ATP7B have been identified, the most common is in Hungary, the
      H1069Q mutation. Genetic screening should only be advised if there is a
      predominant mutation characteristic for the geographic area. The authors discuss
      the modern diagnostic and therapeutic possibilities of Wilson disease.

PMID- 15566073
TI  - [Hundred years anniversary of Gyorgy Ivanovics MD (1904-1980)].

PMID- 15566074
TI  - [Life and work of Lajos Felpeczi Petz MD (1854-1932)].

PMID- 15566075
TI  - Qualitative and quantitative description of myocardial ischemia by means of
      magnetocardiography.
AB  - In the framework of this study quantitative parameters are presented which,
      derived from magnetocardiographic maps, aid in making a conclusion about ischemia
      in the myocardium. The analysis is based on the examination of 86 patients with
      unstable angina, of which 53 exhibited myocardial ischemia with high probability
      (Group I: angiographically proven stenosis of at least 50% in a coronary artery
      of first or second order and positive troponin), while in the 33 other patients
      myocardial ischemia could be ruled out with high probability (Group II:
      angiographically clean coronary bed and normal troponin values). The negative
      predictive value (the probability that there is no myocardial ischemia when the
      magnetocardiogram (MCG) is negative) is 96.2%; the positive predictive value (the
      probability that there is actually coronary heart disease when the
      magnetocardiogram is positive) is 91.2%. A 12-lead ECG taken at the same time as
      the MCG achieved a positive predictive value of 92.8%, but a negative predictive
      value of 53.4%. Consequently, the boundary values of the parameters selected lead
      to a markedly distinct separation between patients with myocardial ischemia from
      those without. For ruling out coronary heart disease in patients with unstable
      angina the MCG is superior to 12-lead ECG.

PMID- 15566076
TI  - [German Artificial Sphincter System--GASS. Development and in vitro evaluation of
      a novel, fully-implantable, highly integrated sphincter prosthesis for therapy of
      high-grade fecal incontinence].
AB  - No highly integrated sphincter prosthesis for therapy of major fecal incontinence
      exists. Therefore, we developed a novel neosphincter, made of polyurethane. The
      GASS consists of a support ring (SR) which includes a fluid reservoir, fixed on
      the outer diameter of the SR, and a multi-chamber occluding cuff (C(int)) on the
      inside diameter. The total inflation volume of C(int) is about 23 cc. The
      integrated micropump based on piezotechnology measures 30x13x1 mm3 (flowrate 1.4
      cc/min, max. backpressure 40,000 Pa) . GASS was evaluated around the external
      sphincter of isolated porcine anal canals. The threshold of continence was
      defined as the inflating volume which water ceased to leak through the area
      occluded by C(int) under an induced rectal pressure of 150 cm H2O. Minimal
      filling volumes maintained continence for liquids against high luminal pressures.
      A low intraanal resting pressure (delta p(anal)) induced by activated GASS
      indicates a little risk of ischemic injury of the anal canal in vivo (median
      delta p(anal) 24.1 mm hg:15 cc vs 46.9 mm hg:21 cc). In summary, a highly
      integrated and efficient high-tech neosphincter for the therapy of major fecal
      incontinence could be realized.

PMID- 15566077
TI  - [Duration of induced seizures during selective pharyngeal brain cooling].
AB  - Whole body hypothermia can be used to treat the injured brain (e.g. after hypoxic
      events). Side effects include hemodynamic instability, coagulopathy and
      infection. Because of these side effects it appears reasonable to cool the brain
      selectively (selective brain cooling, SBC) without changing the core temperature.
      A new animal model was used to demonstrate SBC from the pharynx and to examine
      effects of SBC on the duration of pharmacologically induced seizure activity.
      Sprague-Dawley rats (n=18, 12 successful experiments) were sedated and
      mechanically ventilated. Invasive blood pressure monitoring was instituted and
      blood gases were drawn to evaluate the arterial blood gas status. Electrical
      brain activity was recorded using a microneedle in the extracellular compartment
      of the rat brain cortex. Cooled water was circulated through a small tubing into
      and out of the pharynx of the animals. The cortical as well as the rectal
      temperature were recorded. After the injection of a single dose of bicuculline (1
      mg/kg i.v.) per animal the duration of the induced seizure activity was measured
      and compared with the temperature prior to the induction of seizure activity. The
      cortical blood flow (CBF) was detected using intra tissue Doppler signals in the
      rat cortex in the same location as the EP-study. The influence of a brain
      temperature reduction between 36.5 degrees to 31.5 degrees C on the seizure
      duration was examined. There was a positive correlation between the seizure
      duration and the cortical temperature (r=0.64). Also the CBF was increased during
      seizure activity (p=0.02) and the increase correlated weakly with cortical
      temperature (r=0.18). The core temperature remained in the normothermic range
      (36.9+/-0.7 degrees C) Conclusion: The duration of induced seizures correlates
      with local brain temperature. In the future further studies should examine the
      efficiency of induced (selective) brain cooling to treat prolonged seizure
      activity.

PMID- 15566078
TI  - [Biochemical bone marrow markers and their significance in postmenopausal
      osteoporosis--a new method in the diagnosis of osteoporosis?].
AB  - This study analyzes the qualification of biochemical markers in the diagnosis of
      osteoporosis and evaluates the potential of a multiparametric classification of
      premenopausal and non-osteoporotic as well as osteoporotic postmenopausal women,
      which is based on biochemical marker profiles. For this evaluation data of 29
      women in the age between 28-74 years were used. The classification of
      osteoporosis was done by the trabecular density of the lumbar spine using qCT
      measurements. The biochemical markers of formation and resorption AP, bAP, OC,
      ucOC, PICP, PYD, DPD, NTX, BSP and vitamin K were analyzed on day 1 and 42 in all
      patients. For vitamin K we found significant distribution differences between non
      osteoporotic and osteoporotic women (p<0.005). The crosslinks PYD and DPD showed
      weakly significant differences. All other parameters exhibited non-significant
      results. Vitamin K acted with a sensitivity of 64% and a specificity of 82%. The
      used multiparameter classification process improved sensitivity and specificity
      considerably. The parameter profiles of OC/PYD, vitamin K/PYD and vitamin K/bAP
      revealed the highest sensitivities with specificities of more than 82%.

PMID- 15566079
TI  - Anatomically adapted, HA coated SBG stem--ten years of successful implantation.
AB  - For stable implantation of anatomically conforming femur prostheses,
      modifications that accommodate curving and torsion are necessary. In accordance
      to this concept, the anatomically shaped SBG stem has been developed. The first
      consecutive implantations were evaluated. 194 primary arthroplasties with
      uncemented anatomical, HA coated SBG stems were performed. Mean patient age was
      61 years. 143 patients with 151 (78%) SBG stems were followed-up clinically and
      radiologically after an average of 10 (9-11) years. So far, only one implant had
      to be revised. Survivorship with revision of the femoral component is 99.5% at
      ten years. The mean postoperative Harris Hip Score was 92. Patients over 75 years
      had a score of 89; younger patients under 40 years scored 94. Sclerotic lines
      were seen in zone I or VII in 8%. Minor femoral remodeling (Type 1) occurred
      proximally in 75%. Minor thickening of the femur at the level of the tip of the
      prosthesis could be observed in 27% of the cases. There is no correlation between
      compacta thickening and clinical symptoms (p=0.15). The anatomical shape, the
      oval diameter and the longitudinal grooves secure stable primary fixation.
      Together with the HA coating, which enhances osseointegration, the SBG stem has a
      high success rate in the medium and long term.

PMID- 15566080
TI  - Assessment of the efficacy of a single dose of a recombinant vaccine against West
      Nile virus in response to natural challenge with West Nile virus-infected
      mosquitoes in horses.
AB  - OBJECTIVE: To determine the onset of immunity after IM administration of a single
      dose of a recombinant canarypox virus vaccine against West Nile virus (WNV) in
      horses in a blind challenge trial. ANIMALS: 20 mixed-breed horses. PROCEDURE:
      Horses with no prior exposure to WNV were randomly assigned to 1 of 2 groups (10
      horses/group). In 1 group, a recombinant canarypox virus vaccine against WNV was
      administered to each horse once (day 0). The other 10 control horses were
      untreated. On day 26, 9 treated and 10 control horses were challenged via the
      bites of mosquitoes (Aedes albopictus) infected with WNV. Clinical responses and
      WNV isolation were monitored for 14 days after challenge exposure; antibody
      responses against WNV after administration of the vaccine and challenge were also
      assessed in both groups. RESULTS: Following challenge via WNV-infected
      mosquitoes, 1 of 9 treated horses developed viremia. In contrast, 8 of 10 control
      horses developed viremia after challenge exposure to WNV-infected mosquitoes. All
      horses seroconverted after WNV challenge; compared with control horses, antibody
      responses in the horses that received the vaccine were detected earlier.
      CONCLUSIONS AND CLINICAL RELEVANCE: In horses, a single dose of the recombinant
      canarypox virus-WNV vaccine appears to provide early protection against
      development of viremia after challenge with WNV-infected mosquitoes, even in the
      absence of measurable antibody titers in some horses. This vaccine may provide
      veterinarians with an important tool in controlling WNV infection during a
      natural outbreak or under conditions in which a rapid onset of protection is
      required.

PMID- 15566081
TI  - Effects of season and sample handling on measurement of plasma alpha-melanocyte
      stimulating hormone concentrations in horses and ponies.
AB  - OBJECTIVE: To investigate effects of sample handling, storage, and collection
      time and season on plasma alpha-melanocyte-stimulating hormone (alpha-MSH)
      concentration in healthy equids. ANIMALS: 11 healthy Standardbreds and 13 healthy
      semiferal ponies. PROCEDURE: Plasma alpha-MSH concentration was measured by use
      of radioimmunoassay. Effects of delayed processing were accessed by comparing
      alpha-MSH concentrations in plasma immediately separated with that of plasma
      obtained from blood samples that were stored at 4 degrees C for 8 or 48 hours
      before plasma was separated. Effects of suboptimal handling were accessed by
      comparing alpha-MSH concentrations in plasma immediately stored at -80 degrees C
      with plasma that was stored at 25 degrees C for 24 hours, 4 degrees C for 48
      hours or 7 days, and -20 degrees C for 30 days prior to freezing at -80 degrees
      C. Plasma alpha-MSH concentrations were compared among blood samples collected at
      8:00 AM, 12 noon, and 4:00 PM. Plasma alpha-MSH concentrations were compared
      among blood samples collected in January, March, April, June, September, and
      November from horses and in September and May from ponies. RESULTS: Storage of
      blood samples at 4 degrees C for 48 hours before plasma was separated and storage
      of plasma samples at 4 degrees C for 7 days prior to freezing at -80 degrees C
      resulted in significant decreases in plasma alpha-MSH concentrations. A
      significantly greater plasma alpha-MSH concentration was found in September in
      ponies (11-fold) and horses (2-fold), compared with plasma alpha-MSH
      concentrations in spring. CONCLUSIONS AND CLINICAL RELEVANCE: Handling and
      storage conditions minimally affected plasma alpha-MSH concentrations. Seasonal
      variation in plasma alpha-MSH concentrations must be considered when evaluating
      pituitary pars intermedia dysfunction in equids.

PMID- 15566082
TI  - Correlation between plasma alpha-melanocyte-stimulating hormone concentration and
      body mass index in healthy horses.
AB  - OBJECTIVE: To evaluate the correlation between plasma alpha-melanocyte
      stimulating hormone (alpha-MSH) concentration and body mass index (BMI) in
      healthy horses. ANIMALS: 82 healthy horses. PROCEDURE: Plasma alpha-MSH
      concentration was determined by radioimmunoassay. At the time blood samples were
      collected, body condition scores (BCS) were determined and measurements of girth
      circumference, body length, and height were obtained. Weight was estimated by use
      of the following formula: estimated weight (kg) = [girth (cm)2 x length
      (cm)]/11,877. Body mass index was calculated as estimated weight (kg)/height
      (m)2. RESULTS: A correlation was found between BMI and BCS (rs = 0.60 [95%
      confidence interval (CI), 0.44 to 0.731). A weak correlation was found between
      plasma alpha-MSH concentration and BMI (rs = 0.25 [95% CI, 0.03 to 0.45]) and BCS
      (rs = 0.26 [95% CI, 0.04 to 0.46]). A correlation was found between plasma alpha
      MSH concentration and BMI in horses > or = 10 years old (rs = 0.49 [95% CI, 0.20
      to 0.69]) but not in horses < 10 years old (rs = -0.04). Horses in the upper
      quartile of BMI had significantly greater plasma alpha-MSH concentration (median,
      9.1 pmol/L; range, 2.0 to 95.3 pmol/L) than horses in the lowest quartile of BMI
      (median, 70 pmol/L; range, 3.6 to 15.7 pmol/L). CONCLUSIONS AND CLINICAL
      RELEVANCE: A correlation exists between plasma alpha-MSH concentration and BMI in
      horses. Further study is required to determine whether melanocortin receptor
      defects underlie this correlation or, alternately, whether plasma alpha-MSH
      concentration is simply a correlate of adiposity.

PMID- 15566083
TI  - Preclinical evaluation of a liposome-encapsulated formulation of cisplatin in
      clinically normal dogs.
AB  - OBJECTIVE: To determine the acute and short-term adverse effects of a liposome
      encapsulated form of cisplatin at increasing dosages of up to twice the known
      maximally tolerated dose (MTD) of unencapsulated cisplatin in clinically normal
      dogs. ANIMALS: 4 healthy 2.5-year-old sexually intact female hound-type dogs.
      PROCEDURE: 4 dosages (70, 100, 125, and 150 mg/m2) were evaluated, and the 4 dogs
      received a total of 9 infusions (1 to 3 infusions/dog). Dogs were monitored to
      detect changes in clinical and clinicopathologic status. Evaluations consisting
      of a physical examination, CBC, serum biochemical analysis, and urinalysis were
      performed before and 7 and 21 days after each infusion. RESULTS: Acute
      anaphylactic-like reactions to liposome-encapsulated cisplatin were common but
      clinically manageable. Nephrotoxicosis and substantial myelosuppression, toxic
      effects commonly associated with unencapsulated cisplatin, were not observed in
      dogs treated with liposome-encapsulated cisplatin at dosages equivalent to twice
      the known MTD of unencapsulated cisplatin. CONCLUSIONS AND CLINICAL RELEVANCE:
      Liposome-encapsulated cisplatin can be safely administered to clinically normal
      dogs at dosages of up to 150 mg/m2 without the need for concurrent hydration
      protocols. This was a necessary prerequisite to enable phase I clinical trials in
      dogs with naturally developing cancers that could theoretically benefit from
      escalation in the dosage of cisplatin. Determination of an MTD, cumulative and
      long-term toxic effects, and efficacy can now be conducted in the context of
      phase I trials in tumor-bearing dogs.

PMID- 15566084
TI  - Pharmacokinetics of R(-) and S(+) carprofen after administration of racemic
      carprofen in donkeys and horses.
AB  - OBJECTIVE: To compare plasma disposition of the R(-) and S(+) enantiomers of
      carprofen after IV administration of a bolus dose to donkeys and horses. ANIMALS:
      5 clinically normal donkeys and 3 clinically normal horses. PROCEDURE: Blood
      samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30,
      and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours
      after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed
      in triplicate via high-performance liquid chromatography to determine the
      concentrations of the carprofen enantiomers. A plasma concentrationtime curve for
      each donkey and horse was analyzed separately to estimate noncompartmental
      pharmacokinetic variables. RESULTS: In donkeys and horses, the area under the
      plasma concentration versus time curve (AUC) was greater for the R(-) carprofen
      enantiomer than it was for the S(+) carprofen enantiomer. For the R(-) carprofen
      enantiomer, the AUC and mean residence time (MRT) were significantly less and
      total body clearance (CIT) was significantly greater in horses, compared with
      donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less
      and CIT and apparent volume of distribution at steady state were significantly
      greater in horses, compared with donkeys. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results have suggested that the dosing intervals for carprofen that are used in
      horses may not be appropriate for use in donkeys.

PMID- 15566085
TI  - Investigation of the transmission of Mycobacterium bovis from deer to cattle
      through indirect contact.
AB  - OBJECTIVE: To investigate the infection of calves with Mycobacterium bovis
      through oral exposure and transmission of M. bovis from experimentally infected
      white-tailed deer to uninfected cattle through indirect contact. ANIMALS: 24 11
      month-old, white-tailed deer and 28 6-month-old, crossbred calves. PROCEDURE: In
      the oral exposure experiment, doses of 4.3 x 10(6) CFUs (high dose) or 5 x 10(3)
      CFUs (low dose) of M. bovis were each administered orally to 4 calves; as
      positive controls, 2 calves received M. bovis (1.7 x 10(5) CFUs) via tonsillar
      instillation. Calves were euthanatized and examined 133 days after exposure. Deer
      to-cattle transmission was assessed in 2 phases (involving 9 uninfected calves
      and 12 deer each); deer were inoculated with 4 x 10(5) CFUs (phase I) or 7 x
      10(5) CFUs (phase II) of M. Bovis. Calves and deer exchanged pens (phase I; 90
      days' duration) or calves received uneaten feed from deer pens (phase II; 140
      days' duration) daily. At completion, animals were euthanatized and tissues were
      collected for bacteriologic culture and histologic examination. RESULTS: In the
      low- and high-dose groups, 3 of 4 calves and 1 of 4 calves developed
      tuberculosis, respectively. In phases I and II, 9 of 9 calves and 4 of 9 calves
      developed tuberculosis, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that experimentally infected deer can transmit M. bovis to cattle
      through sharing of feed. In areas where tuberculosis is endemic in free-ranging
      white-tailed deer, management practices to prevent access of wildlife to feed
      intended for livestock should be implemented.

PMID- 15566086
TI  - Comparison of the cognitive palatability assessment protocol and the two-pan test
      for use in assessing palatability of two similar foods in dogs.
AB  - OBJECTIVE: To compare preferences of dogs for 2 similar foods by use of 2
      distinct methods (the cognitive palatability assessment protocol [CPAP] and the 2
      pan test). ANIMALS: 13 Beagles. PROCEDURE: 6 dogs were trained in a 3-choice
      object-discrimination-learning task in which their nonpreferred objects were
      associated with a reward of a lamb-based or chicken-based food. The number of
      choices for each object was used to determine food preferences. Preference of the
      same foods was also assessed by use of a 2-pan test in which all 13 dogs were
      provided the 2 foods in identical bowls. The amount of each food consumed in 10
      minutes was used to determine food preference. RESULTS: All dogs had a noticeable
      preference for the chicken-based food during the CPAP. Once established,
      preferences remained consistent and were not affected by satiety. The 2-pan test
      identified a preference for the chicken-based food in dogs with previous exposure
      to the food but only a weak and nonsignificant preference for the same food in
      dogs without previous exposure. Food preferences in the 2-pan test varied
      considerably. Total food consumption and the ability to detect a preference were
      reduced when dogs were fed prior to testing. CONCLUSIONS AND CLINICAL RELEVANCE:
      The CPAP provides a reliable measure of food preference that requires few test
      subjects. The 2-pan test reveals similar preferences but with variability in data
      that requires larger numbers of subjects and is susceptible to effects from prior
      exposure and feeding of the test foods to the subjects.

PMID- 15566087
TI  - Distribution of vertical forces in the pads of Greyhounds and Labrador Retrievers
      during walking.
AB  - OBJECTIVE: To document peak vertical force (PVF) and vertical impulse (VI) in the
      pads of Greyhounds and Labrador Retrievers. ANIMALS: 8 Greyhounds and 8 Labrador
      Retrievers. PROCEDURE: Velocity and acceleration were restricted to ranges of 0.9
      to 1.1 m/s and -0.1 to 0.1 m/s2, respectively. The PVF and VI measurements were
      collected from digital pad (DP)-2, -3, -4, and -5 and the metacarpal pad (McP) or
      metatarsal pad (MtP) of each limb in each dog. RESULTS: We found no significant
      differences between the left and right forelimbs or hind limbs for any pad in
      either breed. Vertical forces in the forelimb were always greater than those in
      the hind limb. The PVF in the forelimbs of Greyhounds was greatest in DP-3, -4,
      and -5 and DP-3, DP-4, and the MtP in the hind limbs. The VI in Greyhound
      forelimbs was greatest in DP-3, -4, and -5 but greatest in DP-4 in the hind
      limbs. The PVF in the forelimbs of Labrador Retrievers was greatest in the McP,
      whereas in the hind limbs it was greatest in DP-4. The VI in Labrador Retriever
      forelimbs was greatest in DP-3, DP-4, and the McP but greatest in DP-3 and -4 in
      the hind limbs. Significant differences were detected in load distribution
      between the breeds. CONCLUSIONS AND CLINICAL RELEVANCE: This study confirms that
      DP-3 and DP-4 are major weight-bearing pads in dogs. However, loads were fairly
      evenly distributed, and DP-5 and the McP or MtP bear a substantial amount of load
      in both breeds.

PMID- 15566088
TI  - Effect of glomerular filtration rate on clearance and myelotoxicity of
      carboplatin in cats with tumors.
AB  - OBJECTIVE: To characterize the pharmacokinetic disposition of carboplatin and
      determine whether glomerular filtration rate (GFR) could be used to predict
      carboplatin clearance and myelotoxic effects in cats with tumors. ANIMALS: 10
      cats with tumors. PROCEDURE: Glomerular filtration rate was assessed in each cat
      by monitoring plasma clearance of technetium Tc 99m-labeled
      diethylenetriaminepentaacetic acid (99mTc-DTPA). Each cat received carboplatin
      (200 mg/m2 of body surface area) administered as an IV bolus. Plasma platinum
      concentrations were measured via atomic absorption spectrophotometry, and
      pharmacokinetic analysis was performed. A CBC was performed weekly for each cat,
      and the correlation between the area under the concentration-versus-time curve
      (AUC) and the severity of myelosuppression was calculated. Least squares
      regression analysis was performed to determine whether GFR could be used to
      predict plasma platinum clearance (ClPt). RESULTS: For all cats, AUC measurements
      ranged from 0.99 to 4.30 min x mg x mL(-1). Neutrophil concentration nadirs were
      detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/microl.
      The absolute neutrophil concentration at the nadir was inversely correlated with
      AUC. The ClPt was predicted by use of GFR measurements (ClPt = 2.60 x GFR). A
      carboplatin dose prescription model was derived involving AUC, estimated ClPt,
      and body weight in kilograms (BWkg), in which dose = AUC x 2.60(GFR) x BWkg.
      CONCLUSIONS AND CLINICAL RELEVANCE: In cats, an individualized prescription
      strategy for carboplatin administration based on a targeted AUC and determination
      of GFR might more uniformly predict myelosuppression than that predicted by
      conventional dosing based on body surface area.

PMID- 15566089
TI  - Effects of injury to the suspensory apparatus, exercise, and horseshoe
      characteristics on the risk of lateral condylar fracture and suspensory apparatus
      failure in forelimbs of thoroughbred racehorses.
AB  - OBJECTIVE: To assess concurrently the effects of moderate ligamentous suspensory
      apparatus injury (MLSAI), racing-speed exercise, and horseshoe characteristics on
      risk of catastrophic suspensory apparatus failure (SAF) or metacarpal condylar
      fracture (CDY) in forelimbs of racehorses. SAMPLE POPULATION: Cadavers of 301
      Thoroughbred racehorses (108 with SAF, 33 with CDY and 160 control horses).
      PROCEDURE: A cross-sectional epidemiologic study was used to describe
      distributions and relationships between MLSAI, exercise, and horseshoe variables.
      Logistic regression was used to assess potential risk factors for developing SAF
      and CDY. RESULTS: Exercise variables were more highly associated with age than
      height of a steel bar affixed to the ground surface of the front of a horseshoe
      (ie, toe grab) or sex. Marginal associations were detected between MLSAI and age
      and height of toe grab. Higher risk for developing SAF was associated with MLSAI,
      use of a pad on a horseshoe, longer interval since last period of > or = 60 days
      without a race or timed workout (ie, layup), 2 to 5 career races, and higher
      intensity of recent exercise. Higher risk for developing CDY was associated with
      MLSAI, male horses, age between 2 and 5 years, higher intensity of recent
      exercise, and longer interval since layup. CONCLUSIONS AND CLINICAL RELEVANCE:
      Recognition of MLSAI and rehabilitation of affected horses should reduce
      incidence of SAF and CDY. Horses in longterm continuous training with recent high
      intensity exercise are at greater risk for injury. Use of pads in horseshoes was
      associated with SAF, although the relationship may not be causal.

PMID- 15566090
TI  - Dynamic computed tomographic evaluation of the pituitary gland in healthy dogs.
AB  - OBJECTIVE: To determine the contrast enhancement pattern of the pituitary gland
      in healthy dogs via dynamic computed tomography (CT). ANIMALS: 17 dogs.
      PROCEDURE: With each dog in sternal recumbency, transverse CT scans were made
      perpendicular to the skull base from the rostral clinoid processes to the dorsum
      sellae. At the position of the image that contained the largest cross section of
      the pituitary gland, a series of 9 to 11 scans was made during and after IV
      injection of contrast medium (dynamic CT scans). The contrast enhancement pattern
      of the pituitary gland and surrounding arteries was assessed visually and by use
      of time-density curves. RESULTS: After strong enhancement of the maxillary
      arteries, the intracavernous parts of the internal carotid arteries, and the
      communicating arteries of the arterial cerebral circle, there was a strong
      enhancement of the central part of the pituitary gland followed by enhancement of
      its peripheral part. On the last images of the dynamic series of the pituitary
      gland, the central part was hypodense, compared with the peripheral part. Time
      density curves confirmed an early, strong enhancement of the central part and a
      delayed, less strong enhancement of the peripheral part of the gland. CONCLUSIONS
      AND CLINICAL RELEVANCE: The difference in enhancement between the central and
      peripheral parts of the pituitary gland was attributable to a difference in
      vascularization of the neurohypophysis and adenohypophysis, respectively.
      Distortion or disappearance of the strong central enhancement (pituitary flush)
      may be used for the detection and localization of pituitary abnormalities in the
      adenohypophysis.

PMID- 15566091
TI  - Microbiologic findings in feedlot cattle with acute interstitial pneumonia.
AB  - OBJECTIVE: To test the hypothesis that feedlot cattle with acute interstitial
      pneumonia (AIP) have bacterial infection of the lung or liver and concurrent
      bovine respiratory syncytial virus (BRSV) infection significantly more often than
      pen mates without AIP ANIMALS: 39 feedlot cattle with signs consistent with AIP
      and no history of treatment with antimicrobials and 32 healthy control cattle
      from the same pens. PROCEDURES: Lung and liver specimens were obtained postmortem
      for bacterial or mycoplasmal culture and histologic examination; lung tissue was
      assessed for BRSV infection immunohistochemically. RESULTS: Among affected
      cattle, 26 had AIP confirmed histologically. Lung tissue from 11 cattle with AIP
      yielded microbial respiratory tract pathogens on culture; tissues from control
      animals yielded no microbial growth. In 4 cattle with AIP and 2 control animals,
      liver abscesses were detected; bacteria were isolated from abscessed tissue in 3
      and 1 of those animals, respectively. Immunohistochemically, 9 cattle with AIP
      and no control animals were BRSV-positive. Histologically, 9 AIP-affected cattle
      had only acute alveolar damage with exudation, and the other 17 had acute
      exudation with type II pneumocyte hyperplasia. No lesions of AIP were detected in
      control animals. Only 4 AIP-affected cattle had bacterial infection of the lung
      with concurrent BRSV infection. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that microbial respiratory tract pathogens are more common in cattle
      with AIP than in healthy pen mates. Control of bacterial pneumonia late in the
      feeding period may reduce the incidence of AIP at feedlots where AIP is a
      problem.

PMID- 15566092
TI  - Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in
      horses with induced arthritis in the right carpal joint.
AB  - OBJECTIVE: To determine pharmacokinetic-pharmacodynamic (PK-PD) relationships and
      dose effects for meloxicam in horses and to propose a suitable dosage for use in
      clinical studies. ANIMALS: 6 adult horses. PROCEDURE: The study was conducted by
      use of a randomized, Latin-square design. Arthritis was induced in the right
      carpal joint of each horse by administration of Freund's complete adjuvant.
      Various dosages of meloxicam (0, 0.25, 0.5, 1.0, and 2.0 mg/kg, IV) were then
      administered. Validated endpoints including stride length and overall clinical
      lameness score (scale of 0 to 20) were used to assess the effect of meloxicam.
      The dose-effect relationship was quantified by use of a maximum possible effect
      (Emax) model. RESULTS: For stride length (expressed as a relative percentage
      increase from control values), the median effective dose (ED50) was 0.120 mg/kg
      for an Emax of 11.15%. For clinical lameness score (expressed as an absolute
      increase from the control value), the ED50 was 0.265 mg/kg for an Emax of 9.16
      units. The PK-PD analysis allowed calculation of a median effective concentration
      of 130 ng/mL for stride length and 195 ng/mL for lameness score. Use of the Emax
      model predicted a maximal possible increase in effect of 19.5% for stride length
      and 13.91 units for lameness score. For stride length and lameness score, the
      Hill coefficient (slope) was extremely high, which suggested a steep dose-effect
      relationship. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest
      that meloxicam is a potent anti-inflammatory drug in horses. A dosage of 0.6
      mg/kg/d would be appropriate for use in a clinical study.

PMID- 15566093
TI  - Pharmacokinetics of meloxicam in plasma and urine of horses.
AB  - OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal
      anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the
      first phase of the study, horses were administered meloxicam once in accordance
      with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not
      fed). The second phase used a multiple-dose regimen (daily oral administration of
      meloxicam for 14 days), with meloxicam administered at the recommended dosage
      (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of
      validated methods with a limit of quantification of 10 ng/mL for plasma and 20
      ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5
      mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg),
      and terminal half-life was 8.54 +/- 3.02 hours. After oral administration,
      bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed
      horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14
      days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated
      via the urine with a urine-to-plasma concentration that ranged from 13 to 18.
      Concentrations were detected for a relatively short period (3 days) after
      administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results of this study support once-daily administration of meloxicam regardless
      of the feeding status of a horse and suggest a period of at least 3 days before
      urine concentrations of meloxicam reach concentrations that could be used in drug
      control programs.

PMID- 15566094
TI  - Correlation of dominance as determined by agonistic interactions with feeding
      order in cats.
AB  - OBJECTIVE: To determine whether the direction of dominance as determined by
      agonistic interactions away from food was different from the direction of
      dominance as determined by access to a resource in cats. ANIMALS: 28 cats.
      PROCEDURE: Dyadic relationships and hierarchy formed from observation of
      agonistic interactions away from food were compared with those formed from
      interactions at the food bowl. A cat was scored as subordinate to another cat if
      it lost 3 of 3 interactions or lost > or = 75% of the interactions when > 3
      interactions occurred. RESULTS: Cats were observed for 449.4 hours. Hierarchy
      rank determined by agonistic interactions away from food was significantly
      correlated with rank determined by interactions at the food bowl. In 27 of 31
      dyads, the direction of dominance was the same for food bowl and agonistic
      relationships, which was significant. In post hoc analyses, when considering the
      relationship between 2 cats, the heavier cat most likely ranked higher in each
      hierarchy; however, age was not significantly correlated with either hierarchy.
      On the basis of dyadic information, the older cat in a dyad was more often
      dominant in agonistic interactions. Males had a higher mean dominance rank than
      females; however, sex had no effect on rank determined by interactions at the
      food bowl. CONCLUSIONS AND CLINICAL RELEVANCE: Factors influencing dominant
      subordinate relationships are of interest for understanding and treating behavior
      problems such as aggression and resource control. The outcome of agonistic
      interactions away from food was related to, but not perfectly correlated with,
      the outcome of interactions at the food bowl, although winners of those agonistic
      interactions tended to have control of food.

PMID- 15566095
TI  - Comparison of the carbon 13-labeled octanoic acid breath test and ultrasonography
      for assessment of gastric emptying of a semisolid meal in dogs.
AB  - OBJECTIVE: To compare the rate of gastric emptying of a semisolid meal by use of
      the carbon 13-labeled octanoic acid breath test (13C-OBT) and gastric emptying
      ultrasonography (GEU) in dogs. ANIMALS: 10 healthy dogs. PROCEDURE: Food was
      withheld from dogs for 12 hours before ingestion of a test meal (bread, egg, and
      skimmed milk) containing 13C-octanoic acid. The gastric antrum was visualized by
      use of a 6.5-MHz microconvex transducer, and the area of the ellipse defined by
      the craniocaudal and ventrodorsal diameters of the stomach was measured. Samples
      of expired air and antral images were obtained 30 minutes before ingestion of the
      test meal and then every 15 minutes for 4 hours and every 30 minutes for a
      further 2 hours. The half-dose recovery time with the 13C-OBT (t1/2[BT]) and the
      gastric half emtying time with GEU (t50%[GEU]) was calculated. RESULTS: Mean +/-
      SD values for the t1/2(BT) and t50%(GEU) were 3.44 +/- 0.48 hours and 1.89 +/-
      0.78 hours, respectively. A significant correlation was detected between the
      t1/2(BT) and t50%(GEU), although there was a large (1.55 hours) mean difference
      between these indices. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      there was a correlation between the rate of solid-phase gastric emptying assessed
      by use of GEU and the 13C-OBT in dogs. Gastric emptying ultrasonography may be a
      useful, noninvasive method for assessment of the rate of solid-phase gastric
      emptying in dogs.

PMID- 15566096
TI  - Comparison of hepatic in vitro metabolism of the pyrrolizidine alkaloid
      senecionine in sheep and cattle.
AB  - OBJECTIVE: To compare hepatic metabolism of pyrrolizidine alkaloids (PAs) between
      sheep and cattle and elucidate the protective mechanism of sheep. SAMPLE
      POPULATION: Liver microsomes and cytosol from 8 sheep and 8 cattle. PROCEDURE:
      The PA senecionine, senecionine N-oxide (nontoxic metabolite) and 6,7-dihydro-7
      hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP; toxic metabolite) were measured in
      microsomal incubations. The kcat (turnover number) was determined for DHP and N
      oxide formation. Chemical and immunochemical inhibitors were used to assess the
      role of cytochrome P450s, flavin-containing monooxygenases (FMOs), and
      carboxylesterases in senecionine metabolism. The CYP3A, CYP2B, and FMO
      concentrations and activities were determined, in addition to the role of
      glutathione (GSH) in senecionine metabolism. RESULTS: DHP concentration did not
      differ between species. Sheep formed more N-oxide, had higher N-oxide kcat, and
      metabolized senecionine faster than cattle. The P450 concentrations and isoforms
      had a large influence on DHP formation, whereas FMOs had a large influence on N
      oxide formation. In cattle, CYP3A played a larger role in DHP formation than in
      sheep. FMO activity was greater in sheep than in cattle. Addition of GSH to in
      vitro microsomal incubations decreased DHP formation; addition of cytosol
      decreased N-oxide formation. CONCLUSIONS AND CLINICAL RELEVANCE: Hepatic
      metabolism differences alone do not account for the variation in susceptibility
      seen between these species. Rather, increased ruminal metabolism in sheep appears
      to be an important protective mechanism, with hepatic enzymes providing a
      secondary means to degrade any PAs that are absorbed from the rumen.

PMID- 15566097
TI  - Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers
      in Australia.
AB  - OBJECTIVE: To evaluate the haplotype distribution associated with the copper
      toxicosis gene and the segregation of the mutated allele in a Bedlington Terrier
      population in Australia. ANIMALS: 131 Bedlington Terriers. PROCEDURE: Samples of
      DNA and RNA were obtained from each dog. Genetic status of each dog was evaluated
      by use of the DNA markers C04107; single nucleotide polymorphism (SNP), which was
      adjacent to exon 2 of Murr1; and a deletion marker for exon 2. A subgroup of the
      study population was evaluated by use of biochemical and histologic techniques to
      elucidate the correlation between genotype and phenotype. RESULTS: We identified
      a recombination between the C04107 marker and Murr1 and a variation in a
      nucleotide in the splice site of exon 2 in our Bedlington Terrier cohort.
      Furthermore, we identified a novel haplotype associated with copper toxicosis in
      this cohort. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings indicate that the
      deletion of exon 2 was not the sole cause of copper toxicosis, although only exon
      2 deletion of Murr1 has been responsible for copper toxicosis in Bedlington
      Terriers. Although we failed to find a novel mutation in our cohort, we
      identified an affected dog family with an intact exon 2. Furthermore, we found
      that an SNP in the 5' splicing site of exon 2 may or may not be associated with a
      novel mutation of the Murr1 gene or other genes. Loss of linkage between the
      C04107 marker and the Murr1 gene was also identified in a certain family of dogs.

PMID- 15566098
TI  - Comparison of plasma disposition of alkaloids after lupine challenge in cattle
      that had given birth to calves with lupine-induced arthrogryposis or clinically
      normal calves.
AB  - OBJECTIVE: To compare plasma disposition of alkaloids after lupine challenge in
      cattle that had given birth to calves with lupine-induced arthrogryposis and
      cattle that had given birth to clinically normal calves and determine whether the
      difference in outcome was associated with differences in plasma disposition of
      anagyrine. ANIMALS: 6 cows that had given birth to calves with arthrogryposis and
      6 cows that had given birth to clinically normal calves after being similarly
      exposed to lupine during pregnancy. PROCEDURES: Dried lupine (2 g/kg) was
      administered via gavage. Blood samples were collected before and at various time
      points for 48 hours after lupine administration. Anagyrine, 5,6-dehydrolupanine,
      and lupanine concentrations in plasma were measured by use of gas chromatography.
      Plasma alkaloid concentration versus time curves were generated for each
      alkaloid, and pharmacokinetic parameters were determined for each cow. RESULTS:
      No significant differences in area under the plasma concentration versus time
      curve, maximum plasma concentration, time to reach maximum plasma concentration,
      and mean residence time for the 3 alkaloids were found between groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Because no differences were found in plasma
      disposition of anagyrine following lupine challenge between cattle that had given
      birth to calves with arthrogryposis and those that had not, our findings do not
      support the hypothesis that between-cow differences in plasma disposition of
      anagyrine account for within-herd differences in risk for lupine-induced
      arthrogryposis.

PMID- 15566099
TI  - Measurement of total antioxidant capacity in gingival crevicular fluid and serum
      in dogs with periodontal disease.
AB  - OBJECTIVE: To determine whether gingival crevicular fluid (GCF) and serum total
      antioxidant capacities (TACs) correlate with the degree of severity of
      periodontal disease in dogs. ANIMALS: 41 Toy and Miniature Poodles. PROCEDURES:
      After assessment of the degree of severity of naturally occurring periodontitis,
      GCF samples from both maxillary fourth premolars and a blood sample were
      collected from each dog. The condition of the periodontium of the entire
      dentition and at each site of GCF collection was recorded. Clinical parameters
      assessed included plaque index, gingival index, and probing depth. Radiographic
      analysis of alveolar bone level was also performed. Total antioxidant capacity
      was measured in GCF and serum samples by use of a commercial kit. RESULTS: Dogs
      with gingivitis and minimal periodontitis had significantly higher TAC in GCF
      than dogs with advanced periodontitis. Bivariate regression analysis revealed
      significant negative correlations between TAC in GCF and clinical parameters and
      age. The TAC in serum was significantly negatively correlated with the degree of
      gingival inflammation but was not significantly correlated with age. CONCLUSIONS
      AND CLINICAL RELEVANCE: TAC in GCF is related to the degree of severity of
      periodontal disease in dogs. This is likely the result of release of reactive
      oxygen species by activated phagocytes and fibroblasts in the inflamed
      periodontal tissues. The results of our study suggest that the local delivery of
      antioxidants may be a useful adjunctive treatment for periodontitis in dogs.

PMID- 15566100
TI  - Effects of phenylbutazone, indomethacin, prostaglandin E2, butyrate, and
      glutamine on restitution of oxidant-injured right dorsal colon of horses in
      vitro.
AB  - OBJECTIVE: To study the effects of phenylbutazone, indomethacin, prostaglandin E2
      (PGE2), glutamine, and butyrate on restitution of oxidant-injured right dorsal
      colon of horses in vitro. SAMPLE POPULATION: Right dorsal colon from 9 adult
      horses euthanatized for reasons other than gastrointestinal tract disease.
      PROCEDURES: Mucosal segments from the right dorsal colon were injured via
      exposure to HOCl and incubated in Ussing chambers in solutions containing
      phenylbutazone, indomethacin, indomethacin and PGE2, glutamine, and butyrate.
      Transepithelial resistance and mucosal permeability to mannitol were measured,
      and all mucosal segments were examined histologically. RESULTS: The HOCl-injured
      mucosa had lower resistance and higher permeability to mannitol, compared with
      control tissue. Histologic changes were also evident. Resistance of HOCl-injured
      mucosa recovered partially during the incubation period, and glutamine improved
      recovery. Phenylbutazone and indomethacin increased resistance, but these
      increases were not significant. Butyrate and PGE2 had no effects, compared with
      nontreated HOCl-injured tissues. Mucosal permeability to mannitol was lower in
      glutamine-treated tissue, compared with nontreated tissue. Histologic changes
      reflected the resistance and permeability changes. CONCLUSIONS AND CLINICAL
      RELEVANCE: According to our findings, phenylbutazone and indomethacin do not seem
      to interfere with restitution of oxidant-injured mucosa of equine colon in vitro,
      and glutamine could facilitate mucosal restitution.

PMID- 15566101
TI  - Evaluation of a single injection of a sustained-release formulation of moxidectin
      for prevention of experimental heartworm infection after 12 months in dogs.
AB  - OBJECTIVE: To evaluate the efficacy of a single injection of a sustained-release
      formulation of moxidectin in preventing heartworm (Dirofilaria immitis) infection
      for 12 months in dogs. ANIMALS: 14 healthy dogs. PROCEDURE: Group A (nontreated
      control dogs; n = 6) received sterile vehicle administered SC, and group B
      (treated dogs; n = 6) received a sustained-release formulation of moxidectin
      administered SC. All dogs were housed in a heartworm-endemic area for 11.5
      months, and heartworm antigen and modified Knott tests were performed monthly.
      All dogs (including 2 additional control dogs [group C]) were then inoculated
      with infective-stage larvae (L3) of D. immitis, and 4.5 months later, all dogs
      were euthanatized and post-mortem examinations were performed. Adult D. immitis
      were counted and measured, and their age was estimated. RESULTS: All dogs in
      groups A and C were infected with young (4- to 4.5-month old) adult male and
      female D. immitis. No dogs in group B were infected with heartworms. CONCLUSIONS
      AND. CLINICAL RELEVANCE: The age of heartworms recovered suggests that infection
      was the result of experimental inoculation and not natural exposure to mosquitoes
      during the 11.5-month period the dogs resided in a heartworm-endemic area. A
      single SC injection of a sustained-release formulation of moxidectin was
      effective in providing protection against heartworm infection after 12 months in
      dogs. This formulation is a convenient method of heartworm prophylaxis that could
      eliminate the problem of poor owner compliance.

PMID- 15566102
TI  - Changes in the hospital scene.

PMID- 15566103
TI  - 53-years-old with mental status changes.
AB  - D-lactic acidosis, a complication of short bowel syndrome, presents with a
      variety of neurological symptoms and metabolic acidosis. Treatment is hydration,
      replacement of nutritional deficiency replacement, and selective antibiotics.
      Prevention entails complex carbohydrate diet and vitamin and mineral supplements.

PMID- 15566104
TI  - Tubo-ovarian abscess: diagnosis, medical and surgical management.
AB  - Tubo-ovarian abscess (TOA), a serious manifestation of pelvic inflammatory
      disease, has been treated with aggressive surgical therapy. With improvements in
      antibiotic therapy, laparoscopic surgery and interventional radiological
      techniques have lessened the need for radical surgical treatment in stable
      patients.

PMID- 15566105
TI  - The valid informed consent-treatment contract in chronic non-cancer pain: its
      role in reducing barriers to effective pain management.
AB  - The Valid Informed Consent-Treatment Contract is an effective and ethical guide
      for a physician's care of the patient with chronic non-cancer pain.

PMID- 15566106
TI  - Primary hyperparathyroidism: is there anything new?
AB  - Primary hyperparathyroidism remains the most common cause of hypercalcemia
      encountered in outpatient practice. Management of the asymptomatic patient with
      mild disease remains controversial. Surgery is the only curative therapy, and
      minimally invasive procedures are now possible.

PMID- 15566107
TI  - The diagnosis and management of anaphylaxis.
AB  - Anaphylaxis is amongst the most frightening reactions that any physician will
      face. What often separates life and death is the acute management, including the
      proper use of epinephrine. In this review, the differential diagnosis and
      management plan are outlined.

PMID- 15566108
TI  - Appropriate use of the carbapenems.
AB  - The carbapenems are a group of broad-spectrum beta-lactam antibiotic agents of
      which there are three parenteral preparations currently available in South
      Africa, namely imimpenem/cilastatin, meropenem and ertapenem. Owing to the fact
      that imipenem/cilastatin and meropenem have a broad spectrum of activity that
      includes Pseudomonas and Acinetobacter species, they are ideal antibiotics for
      treatment of severe nosocomial infections. In contrast, ertapenem has limited in
      vitro activity against the latter non-fermentative gram-negative bacteria and is
      therefore more suitable for the treatment of certain severe community-acquired
      infections. This statement arises out of concerns about the general abuse of
      antibiotics such as the carbapenems, with the primary intention of highlighting
      the appropriate use of these agents.

PMID- 15566109
TI  - TB: keeping an ancient killer at bay.

PMID- 15566110
TI  - Part II: Tumor markers from A to Z.

PMID- 15566111
TI  - Resolving discordant samples in clinical laboratory practice.

PMID- 15566112
TI  - CEO Hakim's SCC Soft Computer stays ahead of the curve.

PMID- 15566113
TI  - To shred or not to shred?

PMID- 15566114
TI  - Folks who drill together, save together.

PMID- 15566115
TI  - Iraq war poses challenge for medical supply chain.

PMID- 15566117
TI  - Senators mull tighter regulation of GPOS.

PMID- 15566116
TI  - IV prices moving up in 2005.

PMID- 15566118
TI  - Medicare demonstration project creeping to the starting line.

PMID- 15566119
TI  - Capitation rebound spurred by use of information technology, greater acceptance
      by physicians.

PMID- 15566120
TI  - Disclosing capitation deals increases trust of health plans, study says.

PMID- 15566121
TI  - Follow these 5 'laws' to ensure success in capitation.

PMID- 15566122
TI  - What's your diagnosis? Osteoid osteoma.

PMID- 15566123
TI  - Damage control in orthopedic surgery: fad or fact?

PMID- 15566124
TI  - Treatment of supracondylar humeral fractures in children using external fixation.

PMID- 15566125
TI  - Fixation of distal tibial fractures with intraarticular extension using double
      overlapping plates.

PMID- 15566126
TI  - Postoperative hypertension.

PMID- 15566127
TI  - Two-year results after exchange shoulder arthroplasty using inverse implants.

PMID- 15566128
TI  - Prolonged external fixation of the tibia.

PMID- 15566129
TI  - Effects of backpack carrying in children.

PMID- 15566130
TI  - Comparison of intramedullary nailing of distal third tibial shaft fractures:
      before and after traumatologists.
AB  - We hypothesized that less malalignment and complications occur with
      intramedullary nailing of distal third tibia fractures (42A, B, C) after the
      implementation of orthopedic trauma surgeons to this level II community hospital.
      We also hypothesized that patients with < or =5 degrees of malalignment have
      poorer function as measured by the MODEMS functional outcome scale. Two cohorts
      of distal third tibia fractures were identified by discharge diagnosis or by the
      Orthopaedic Trauma Association database. Group I (n = 39) patients were
      stabilized with an intramedullary nail by community orthopedic surgeons. Group II
      (n = 18) patients were treated by orthopedic trauma surgeons. In Group I
      (community), 9 (23%) patients treated by the community surgeons exhibited >5
      degrees of angulation in at least one direction. Five (13%) of these patients
      displayed angulation in more than one direction, and 3 of these patients
      exhibited >10 degrees of angulation. In Group II (trauma) 1 (5%) patient had >5
      degrees angulation in any plane (P < .05). No differences were noted in time to
      union, nonunion, delayed union, hardware failure or infections between the two
      groups. Functional outcomes were assessed using the MODEMS lower limb module. In
      comparison of the patients with and without significant angulation, the P value
      for bodily pain was 0.042. Patients treated by the community orthopedic surgeons
      had a higher incidence of malalignment, as compared to those treated by
      orthopedic trauma specialists.

PMID- 15566131
TI  - The efficacy of a single daily dose of enoxaparin for deep vein thrombosis
      prophylaxis following total knee arthroplasty.
AB  - Deep vein thrombosis (DVT) is a major risk following total knee arthroplasty
      (TKA). This prospective outcomes study evaluates the efficacy of enoxaparin 40 mg
      once daily for 7 days after TKA, by documenting symptomatic and asymptomatic
      outcomes using bilateral lower extremity duplex ultrasound upon hospital
      discharge and on postoperative day 21 (+/-2). In 60 extremities, duplex
      ultrasound demonstrated a DVT prevalence of 16.7% (10) on the day of discharge
      and of 11.7% (7) on postoperative day 21. No new DVT or propagation of distal to
      proximal DVT were noted. For this small cohort, enoxaparin 40 mg daily
      demonstrates effective prophylaxis for DVT in TKA patients.

PMID- 15566132
TI  - Effect of rofecoxib on pain caused by osteoid osteoma.
AB  - In a prospective study, nine patients with osteoid osteoma were treated with a
      selective cyclooxygenase-2 inhibitor (rofecoxib). Patient pain perception with no
      treatment, with conventional nonsteroidal anti-inflammatory drug (NSAID)
      treatment, and with rofecoxib therapy was compared using a visual analog scale.
      Tumor response was also monitored by radiographs, computed tomography, and bone
      scintigraphy. In all cases, pain diminished on administration of rofecoxiib in
      comparison to conventional NSAIDs (P < .05). Four patients underwent surgery
      whereas in the remaining five patients, bone scintigraphy showed reduced uptake
      after 6 months. In four patients who were retested at 12 months,scintigraphy
      values were normal. These four patients are currently asymptomatic and are not
      receiving any treatment, whereas the fifth patient is still receiving therapy.

PMID- 15566133
TI  - The effect of pulsed ultrasound in the treatment of tibial stress fractures.
AB  - Tibial stress fractures commonly occur in athletes and military recruits. This
      prospective, randomized, double-blind clinical study sought to determine whether
      pulsed ultrasound reduces tibial stress fracture healing time. Twenty-six
      midshipmen (43 tibial stress fractures) were randomized to pulsed ultrasound or
      placebo treatment. Twenty-minute daily treatments continued until patients were
      asymptomatic with signs of healing on plain radiographs. The groups were not
      significantly different in demographics, delay from symptom onset to diagnosis,
      missed treatment days, total number of treatments, or time to return to duty.
      Pulsed ultrasound did not significantly reduce the healing time for tibial stress
      fractures.

PMID- 15566134
TI  - Proximal fifth metatarsal stress fracture treated by early open reduction and
      internal fixation.

PMID- 15566135
TI  - Palmar dislocation of the scaphoid and lunate as a unit.

PMID- 15566136
TI  - Symptomatic degenerative disk disease following posterior spinal fusion.

PMID- 15566137
TI  - New principle of magnetophoretic velocity mass analysis.
AB  - We propose a novel principle of velocity mass analysis of a micro-particle using
      magnetophoretic force. The new method can determine the mass of a particle from
      its magnetophoretic velocity change in a high magnetic field gradient in a low
      viscous medium such as air. In the present study, the new principle was
      demonstrated by the magnetophoretic acceleration of an aqueous manganese(II)
      chloride micro-droplet and the deceleration of a water micro-droplet in the
      atmosphere. The observed velocity change was analyzed taking into account the
      mass of the droplet through the acceleration term of the equation of motion. The
      experimental results proved that the inertia force in the magnetophoretic
      velocity of a micro-particle could be detected in air. The present method
      provided an innovative mass analysis method without any ionization of the sample.

PMID- 15566138
TI  - Measurement of circular dichroism spectra of liquid/liquid interface by
      centrifugal liquid membrane method.
AB  - The direct measurement of the circular dichroism (CD) spectra of liquid/liquid
      interface has been achieved for the first time by the centrifugal liquid membrane
      (CLM) method combined with a conventional CD spectropolarimetry. In the sample
      chamber of the CD spectropolarimeter, a cylindrical glass cell containing small
      amounts of organic and aqueous phases was rotated at ca. 7000 rpm to generate a
      two-phase liquid membrane with a high specific interfacial area. The CD spectra
      of the J-aggregate of protonated 5,10,15,20-tetraphenylporphyrin formed at the
      toluene/sulfuric acid interface in the rotating cell have been measured. The
      results demonstrated the novelty and advantages of this method.

PMID- 15566139
TI  - New approaches to liquid interfaces through changes in the refractive index and
      nonlinear susceptibility utilizing ultrashort laser pulses.
AB  - Molecules in inhomogeneous liquid environments, such as air/liquid,
      liquid/liquid, solid/liquid interfaces interact with each other specifically, and
      sometimes form characteristic structures and emerge unique properties. Here, we
      introduce two newly developed spectroscopic techniques, the total-internal
      reflection ultrafast transient lens method (TIR-UTL) and second harmonic
      generation-coherent vibrational spectroscopy (SHG-CVS), to investigate the
      characteristic behaviors of molecules in such inhomogeneous environments. TIR-UTL
      probes the refractive-index change with sub-picosecond resolution and provides
      information on ultrafast changes in the population, density, and thermal
      properties, such as temperature increase and energy transfer from the solute
      molecules to the surrounding solvent molecules. On the other hand, SHG-CVS probes
      nonlinear susceptibility changes at the interfacial areas, and is expected to
      provide spectroscopic information on the low-frequency vibrational modes that
      reflect the corrective motion of the molecules in such an inhomogeneous
      environment. These new approaches are based on pump-probe techniques utilizing
      (ultra) short laser pulses. They are expected to provide further information on
      inhomogeneous environments from the viewpoints of solute-solvent interactions,
      changes in the molecular orientation, and the corrective motion of molecules at
      liquid interfaces.

PMID- 15566140
TI  - Dynamic behaviors of molecular assemblies at liquid/liquid interfaces studied by
      time-resolved quasi-elastic laser scattering spectroscopy.
AB  - The dynamic behaviors of molecular assemblies at two immiscible liquid interfaces
      are intriguing topics in many fields of science and technology. However, it is
      generally difficult to investigate the dynamic behaviors of such molecular
      assemblies because of the buried nature of liquid/liquid interfaces. In the
      present paper, our recent investigations on dynamic behaviors of various
      molecular self-assemblies at liquid/liquid interfaces are reviewed. We monitored
      dynamic behaviors of the molecular assemblies by time-resolved quasi-elastic
      laser scattering (TR-QELS) and fluorescent spectroscopy. The former method allows
      us to monitor the change in interfacial tension with millisecond time-resolution.
      As molecular assemblies, bis(2-ethylhexyl)sulfosuccinate (AOT) microemulsion,
      phospholipid biomembrane models, and liposome-DNA complexes have all been
      studied, since they are relevant in material sciences and biological
      technologies. At liquid/liquid interfaces, these molecular assemblies showed
      characteristic behaviors. We review the finding of rebound response of the
      interfacial tension at the liquid/liquid interface induced by the adsorption of
      the AOT microemulsion. We monitored the hydrolysis reaction of phospholipid
      biomembrane models formed at oil/water interfaces, observing the different types
      of behavior of liposome-DNA complexes at biomembrane models with different kinds
      of phospholipids.

PMID- 15566141
TI  - Chemical oscillation with periodic adsorption and desorption of surfactant ions
      at a water/nitrobenzene interface.
AB  - Chemical oscillations with periodic adsorption and desorption of surfactant ions,
      alkyl sulfate ions, at a water/nitrobenzene interface have been investigated. The
      interfacial tension was measured with a quasi elastic laser scattering (QELS)
      method and the interfacial electrical potential was obtained. We found that this
      oscillation consists of a series of abrupt adsorptions of ions, followed by a
      gradual desorption. In addition, we observed that each abrupt adsorption was
      always accompanied by a small waving motion of the liquid interface. From the
      analysis of the video images of the liquid interface or bulk phase, we could
      conclude that each abrupt adsorption is caused by nonlinear amplification of mass
      transfer of ions from the bulk phase to the liquid interface by a Marangoni
      convection, which was generated due to local adsorption of the surfactant ions at
      the liquid interface that resulted in the heterogeneity of the interfacial
      tension. In the present paper, we describe the mechanism of the chemical
      oscillation in terms of the hydrodynamic effect on the ion adsorption processes,
      and we also show the interfacial chemical reaction with ion exchange during the
      ion desorption process.

PMID- 15566142
TI  - Magnetic field enhanced microextraction rate of europium(III) with 2
      thenoyltrifluoroacetone and oxalate at dodecane-water interface.
AB  - A microscopic system for the observation of reactions at a liquid-liquid
      interface was established, to which strong magnetic fields (0-0.4 T) could be
      applied with permanent magnets. In situ observation for the interfacial
      extraction of fluorescent and paramagnetic Eu(III) ion with 2
      thenoyltrifluoroacetone (Htta) in dodecane was carried out. In the presence of
      oxalate (ox2-), micro-aggregates of Eu(III)-tta-ox complexes were generated in
      the aqueous phase before its extraction. When the micro-aggregates diffused to
      the dodecane-water interface, Eu(tta)3 was extracted with excess Htta in the
      dodecane phase. The microextraction process of the aggregates was observed as
      random flashes of Eu(tta)3 fluorescence at the dodecane-water interface. The
      single flash contained about 10(-16)-10(-14) mol of Eu(III). An application of
      magnetic fields made the flash frequency increase, which corresponded to an
      enhancement of interfacial Eu(III) extraction rate. The enhancement effect was
      attributable to the magnetophoresis of the paramagnetic microaggregates to the
      dodecane-water interface.

PMID- 15566143
TI  - Adsorption behavior of lauric acid at heptane/water interface as studied by
      second harmonic generation spectroscopy and interfacial tensiometry.
AB  - Interfacial tensiometry and second harmonic generation (SHG) spectroscopy were
      applied to examine the adsorption behavior of lauric acid (LA) at a heptane/water
      interface. From interfacial tensiometry measurements, the adsorption kinetics of
      LA was revealed to be diffusion-controlled, and the adsorption constant of LA was
      estimated to be 9.6 x 10(4) M(-1). The adsorption isotherms obtained by SHG
      measurements were analyzed by taking account of both the molecular orientation of
      LA at the interface and a surface electric field generated by the adsorbed LA
      layer. It was confirmed that the carboxylic groups of adsorbed LA molecules were
      well ordered at the heptane/water interface and the orientation of the
      carboxylate group was invariant during the adsorption process.

PMID- 15566144
TI  - Kinetic analysis of distribution of weak acid in an oil-gelatin
      microcapsule/water system studied by microcapillary injection and microabsorption
      methods.
AB  - The distribution of anthracene-9-carboxylic acid across dibutyl phthalate/gelatin
      membrane/water interface of a single microcapsule was analyzed using
      microcapillary manipulation and microabsorption methods. The partitioning ratio
      and the distribution rate in the microcapsule/water system were measured for
      various pH values in the water phase. Results were compared with those in the
      dibutyl phthalate/water system in the absence of the gelatin membrane. The
      distribution rate could be analyzed on the basis of a first-order type reaction.
      The observed rate constant was linearly proportional to the inverse of the
      microcapsule radius, indicating that the distribution rate is limited by
      interfacial mass transfer. Analysis of the pH dependence of the interfacial mass
      transfer rate suggests that the mass transfer of the neutral species of
      anthracene-9-carboxylic acid (AnH) competes with the ion transfer of the
      dissociated species (An-) at the liquid/liquid interface in the gelatin membrane
      of the microcapsule.

PMID- 15566145
TI  - Interfacial adsorption state of protonated lipophilic porphyrins in a liquid
      liquid system by using reflection spectrometry.
AB  - Analysis by reflection spectrometry was performed to clarify the interfacial
      adsorption of protonated lipophilic tetraphenylporphyrin derivatives in a
      dodecane-aqueous sulfuric acid system, and to confirm the utility of partial
      reflection spectroscopy. Interfacial adsorption was not observed for porphyrins
      substituted at the 2,6 positions of meso-phenyl groups, suggesting that the
      substituents prevent porphyrins from forming aggregates by steric hindrance.
      Polymorphous J-aggregates of acid dications were produced by tetra-p
      tolylporphyrin with a saturated interfacial molecular density of 1.0 x 10(-10)
      mol cm(-2), which could yield 48 degrees as a mean tilting angle of the pyrrole
      ring plane from the interface normal. Partial-reflection spectrometry can provide
      sensitive detection and molecular orientation analysis of interfacial adsorbates.

PMID- 15566146
TI  - Adsorption and desorption behaviors of cationic liposome-DNA complexes upon
      lipofection in inside and outside biomembrane models using a dynamic quasi
      elastic laser scattering method.
AB  - The dynamic behaviors of cationic liposome-DNA complexes in inside and outside
      biomembrane models upon lipofection were investigated using the time-resolved
      quasi-elastic laser scattering (QELS) method. Inside and outside biomembrane
      models with similar phospholipid compositions to those in living cells were
      formed at a tetradecane/phosphate buffered saline (TD/PBS) interface. Cationic
      liposome-DNA complexes were injected into the buffer subphase, and their
      adsorption/desorption behaviors at the biomembrane models were monitored through
      changes in the interfacial tension. We found that the adsorption rate of the
      complexes increased 2.6 times more in the outside model than in the inside one.
      The adsorption rate of DNA alone did not show a remarkable difference from one
      side to the other; however, the adsorption rate of the cationic liposome alone
      showed a similar tendency to that of the liposome-DNA complex. These results
      indicated that the difference in lipid composition induced a different dynamic
      behavior of exogenous biomolecules and that the cationic liposomes played an
      important role in the faster incorporation of DNA into cells upon lipofection.

PMID- 15566147
TI  - Complex formation of copper(II) and iron(II) with octadecyloxythiazolylazophenol
      at the heptane-water interface.
AB  - The complex formation of Cu(II) and Fe(II) with a hydrophobic ligand, 5
      (octadecyloxy)-2-(2-thiazolylazo)phenol (TARC18), was investigated in the
      heptane/water system by the high-speed stirring spectrometry and the micro-two
      phase flow ESI/MS method. At first, the dissociation constant of TARC18 at the
      heptane/water interface was determined as pKa = 7.11. The interfacial
      complexation of the ligand with Cu(II) and Fe(II) under stirred conditions
      progressed with an increase of the pH. The experimental results showed that a 1:1
      complex of Cu(II) and TARC18 was formed at the interface, but was hardly
      extracted into the heptane phase. On the other hand, the 1:2 complex of Fe(II)
      with TARC18 formed at the interface was significantly extracted into the heptane
      phase. The extraction constants and interfacial complex formation constants were
      estimated for the two systems from the experimental results, and all of the
      reaction schemes, including the interfacial reactions, were elucidated.

PMID- 15566148
TI  - Self-assembly and subsequent accumulation of lipid nanotubes at oil/water
      interfaces.
AB  - We utilized oil/water interfaces as a new field to produce lipid nanotubes
      (LNTs), which are formed by the self-assembly of lipid molecules, and possess
      hollow nanometer-wide cylindrical structures. Compared to the self-assembling
      field in bulk water, oil/water interfaces produced shorter lipids nanotubes less
      than 10 microm long more efficiently. In addition, we found that the oil/water
      interface accumulates lipid nanotubes spontaneously. This methodology is
      favorable to fabricate LNTs as new nano-fluidic devices, or sensors that require
      accumulation and alignment in two dimensions.

PMID- 15566149
TI  - Electroneutrality coupling of electron transfer at an electrode surface and ion
      transfer across the interface between thin-layer of 1-octyl-3-methylimidazolium
      bis(perfluoroalkylsulfonyl)imide covering the electrode surface and an outer
      electrolyte solution.
AB  - The electrode reaction of decamethylferrocene (DMFc) dissolved in a thin layer of
      a room-temperature molten salt (RTMS), 1-octyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (C8mimC1C1N) or 1-octyl-3-methylimidazolium
      bis(pentafluoroethylsulfonyl)imide (C8mimC2C2N), on a self-assembled monolayer
      modified gold electrode is coupled with the ion transfer across the interface
      between the RTMS and the outer aqueous solution (W) to give a voltammogram whose
      shape resembles a voltammogram of a simple one-electron transfer process. The
      electroneutrality of the RTMS layer during the oxidation of DMFc to
      decamethylferricenium ion is maintained by the concomitant dissolution of C8mim+
      ion from the RTMS phase to the W phase, and the reduction of
      decamethylferricenium ion to DMFc is accompanied by the transfer of either C1C1N-
      or C2C2N- from RTMS to W. The midpoint potential of the voltammogram varies with
      the concentration of the salt in the aqueous phase, C8mimCl or LiCnCnN (n = 1 or
      2), in a Nernstian manner, showing that the phase-boundary potential between the
      RTMS and the W is controlled by the partition of these ions. Although the phase
      boundary potential across the RTMS / W interface is Nernstian with respect to the
      ions common to both phases at the equilibrium, the polarization at the RTMS / W
      interface under current flow distorts the shape of the voltammograms, resulting
      in a wider peak separation in the voltammogram.

PMID- 15566150
TI  - Facilitated sulfate transfer across the nitrobenzene-water interface as mediated
      by hydrogen-bonding ionophores.
AB  - Facilitated SO4(2-) transfers by hydrogen bond-forming ionophores are
      investigated across the nitrobenzene (NB)-water interface by using polarography
      with a dropping electrolyte electrode. Bis-thiourea 1, alpha,alpha'-bis(N'-p
      nitrophenylthioureylene)-m-xylene, is found to significantly facilitate the
      transfer of the highly hydrophilic SO4(2-) whereas its counterpart, N-(p
      nitrophenyl)-N'-propylthiourea (ionophore 2), cannot. In contrast to the
      predominant formation of a 1:1 complex with SO4(2-) in the bulk NB phase, the
      SO4(2-) transfer assisted by 1 is indeed based on the formation of a 1:2 complex
      between SO4(2-) and ionophore, even under the condition of [SO4(2-)]aq >> [1]org.
      Such an exclusive formation of the 1:2 (SO4(2-) to ionophore) complex at the NB
      water interface is not observed with structurally similar bis-thiourea 3,
      alpha,alpha'-bis(N'-phenylthioureylene)-m-xylene, where p-nitrophenyl moietes of
      bis-thiourea 1 are simply replaced by phenyl groups. The facilitated transfer of
      SO4(2-) with bis-thiourea 1 is further compared to that of HPO4(2-) and H2PO4-
      across the NB-water interface, which was previously shown to be assisted by 1
      through the formation of the 1:1 and 2:1 (anion to ionophore) complexes,
      respectively. On the basis of these examinations, unique binding behaviors of
      hydrogen bond-forming ionophores at the NB-water interface are discussed, with a
      view towards development of ionophore-based anion-selective chemical sensors.

PMID- 15566151
TI  - A true electron-transfer reaction between 5,10,15,20-tetraphenylporphyrinato
      cadmium(II) and the hexacyanoferrate couple at the nitrobenzene/water interface.
AB  - The ability of some metal complexes of 5,10,15,20-tetraphenylporphyrin (TPP) to
      give a voltammetric wave due to the heterogeneous electron transfer (ET) at a
      nitrobenzene (NB)/water (W) interface has been examined. The previously-proposed,
      electron-conductor separating oil-water (ECSOW) system has been successfully
      employed to find that the TPP complex with cadmium(II) added to NB gives a well
      defined, reversible wave for the heterogeneous (i.e., "true") ET with the
      hexacyanoferrate couple in W. A digital simulation analysis has entirely excluded
      the possibility of the ion-transfer mechanism due to the homogeneous ET in W. The
      a.c. impedance method has then been used to determine the kinetic parameters
      including the standard rate constant k0 (= 0.10 cm M(-1) s(-1)) and the transfer
      coefficient alpha (= 0.53 at the half-wave potential). These values are in good
      agreement with those predicted from the Marcus theory with the assumption that
      the heterogeneous ET due to molecular collision occurs at the "sharp" NB/W
      interface.

PMID- 15566152
TI  - Photoinduced electron transfer of 5,10,15,20-tetraphenylporphyrinato zinc(II) at
      the polarized water/1,2-dichloroethane interface.
AB  - The photocurrent at the polarized water/1,2-dichloroethane (DCE) interface was
      successfully observed in the presence of a lipophilic sensitizer, 5,10,15,20
      tetraphenylporphyrinato zinc (ZnTPP), in the organic phase. The photocurrent
      transient responses were apparently affected by the employed organic supporting
      electrolyte: tetrapenthylammonium tetraphenylborate (TPnATPB) or
      tris(tetraoctylammonium)tungstophosphate ((TOcA)3PW12O40). The photocurrent
      measured in the TPnATPB system exhibited rather slow responses associated with
      the ion transfer of photoproducts. On the other hand, the photoinduced
      heterogeneous electron transfer could be observed in the use of (TOcA)3PW12O40.
      The photocurrent intensity in the (TOcA)3PW12O40 system exhibited an apparent pH
      dependence and the photoreduction of hydrogen ions probably took place at the
      water/DCE interface. By analyzing the real and imaginary components of the
      photocurrent depending on the photoexcitation frequency, we roughly estimated the
      phenomenological rate constants of the product separation (k(ps)) and
      recombination (k(rec)) processes as log(k(ps)/s(-1)) = 1.5 +/- 0.2 and
      log(k(rec)/s(-1)) = 1.8 +/- 0.1, respectively.

PMID- 15566153
TI  - Voltammetric study of the transfer of polyammonium ions at nitrobenzene / water
      interface.
AB  - The transfer of polyammonium ions, poly[(dimethylimino)-1,6-hexanediyl] (n = 140,
      n being the degree of polymerization) ion and poly[(dimethylimino)(2-oxo-1,2
      ethanediyl)imino-alpha,omega-alkanediylimino(1-oxo-1,2-ethanediyl)(dimethylimino)
      alpha',omega'-alkanediyl] ([-N+ (CH3)2CH2CONH(CH2)x NHCOCH2N+ (CH3)2(CH2)y-]n, x
      = 2, 3, 4, or 6, y = 3 or 6, and n = 30-130) ions, at a polarizable nitrobenzene
      / water interface has been studied by normal pulse voltammetry and cyclic
      voltammetry. Despite the polydispersity of the preparations, by normal pulse
      voltammetry, an S-shaped current-potential curve with a well-defined limiting
      current, and, by cyclic voltammetry, a pair of anodic and cathodic peak currents
      due to the transfer of polyammonium ions across the interface were observed
      within the potential window. The voltammetric behavior is described. Also, the
      effect of ion-pair formation of the polyammonium ions with supporting electrolyte
      anions in nitrobenzene- and water-phases on the half-wave or midpoint potential
      of the ion-transfer, and the relation between the structure of the polyammonium
      ions and the transfer potentials are discussed.

PMID- 15566154
TI  - Photoinduced redox cycle of riboflavin at a water/oil interface.
AB  - A photoinduced redox reaction cycle of Riboflavin (RF) at a water/CCl4 interface
      was studied directly by means of both steady-state and time-resolved total
      internal reflection (TIR) fluorescence spectroscopies. The TIR fluorescence
      spectrum of RF observed at the water/CCl4 interface with the maximum wavelength
      of 517 nm was assigned to the pi-pi* transition from the excited singlet-state of
      the isoalloxazine chromophore in RF. Upon prolonged laser irradiation (400 nm) in
      the presence of N,N-dioctadecyl-[1,3,5]triazine-2,4,6-triamine (DTT) as a guest
      for RF in the CCl4 phase, on the other hand, a new TIR fluorescence band appeared
      at around 480 nm. Furthermore, the fluorescence intensity at around 480 nm
      increased in the presence of acetic acid in the water phase. Detailed studies
      demonstrated that the new fluorescence band should be ascribed to 1,5
      dihydoroflavin (RFH2). The present results indicated that RFH2 was produced
      through the photoreaction of the RF-DTT hydrogen-bonded complex formed at the
      water/CCl4 interface, whose reaction mechanisms were discussed on the basis of
      the results observed by fluorescence spectra/dynamics measurements under the TIR
      conditions as well as by transient absorption spectroscopy.

PMID- 15566155
TI  - Lanthanoid element recognition on surface-imprinted polymers containing
      dioleylphosphoric acid as a functional host.
AB  - Surface-imprinted polymers have been newly developed for the separation of
      lanthanoid elements: i.e. La(III), Ce(III), and Dy(III). The imprinted polymers
      were prepared by surface template polymerization with dioleylphosphoric acid,
      which exhibits a high affinity to lanthanoids, as a functional host molecule.
      Separation behavior of La(III), Ce(III) and Dy(III) was investigated with the
      imprinted polymers, and the imprinting effect of the polymers was evaluated in
      comparison with that of the unimprinted polymers and also with a conventional
      solvent extraction method for the same lanthanoid ions. The results indicate that
      the increase of selectivity for Dy(III) compared to the rest of the ions by the
      surface-imprinted polymers originated from a synergistic effect of both the
      affinity with the functional host molecule in nature and the size exclusion by
      the cavity formed on the polymer surface.

PMID- 15566156
TI  - Oligocarbazoles as ligands for lead-selective liquid membrane electrodes.
AB  - Oligocarbazoles have been applied as new ionophores in liquid membrane electrodes
      (ISEs) destined for lead(II) determination in water samples. The oligocarbazole
      containing ISEs demonstrated a close-to-Nernstian potentiometric response towards
      Pb2+ in the activity range 10(-7)-10(-2) M. The selectivity coefficients measured
      by the matched potential method (MPM) confirmed their good selectivity against
      common interfering mono- and doubly charged cations. The oligocarbazole
      containing ISEs do not respond towards protons. Their applicability has been
      checked by performing the recovery test while using a sample of wastewater.

PMID- 15566157
TI  - Development of a new experimental system for monitoring biomembrane reactions:
      combination of laser spectroscopic techniques and biomembrane models formed at an
      oil/water interface.
AB  - We present a new experimental system to observe reactions in biomembranes by
      combining laser spectroscopic techniques with phospholipid monolayers formed at
      oil/water interfaces. The system can monitor reactions through changes in
      interfacial tension at oil/water interfaces induced by the reactions under non
      destructive and non-contact conditions. In addition, oil/water interfaces with
      defined areas can define the composition of different kinds of phospholipids.
      Furthermore, the system allows using, as an oil phase, alkanes whose number of
      carbon atoms is close to the number of the alkyl chains of phospholipids in
      biomembranes (C > or = 16). We demonstrated the hydrolysis reaction in DPPC
      (dipalmitoyl phosphatidylcholine)/DPPS (dipalmitoyl phosphatidylserine)-mixed
      monolayers by phospholipase A2 by using the system.

PMID- 15566158
TI  - Mutation detection in the drug-resistant hepatitis B virus polymerase gene using
      nanostructured reverse micelles.
AB  - The emergence of drug-resistant hepatitis B virus (HBV) has been reported in
      patients with prolonged administration of lamivudine, which is a potent drug for
      the prevention of HBV infection. Lamivudine-resistant HBV has several types of
      mutations at the YMDD motif of its DNA polymerase. We successfully demonstrated
      that monitoring the hybridization behavior in nanostructured reverse micelles
      enables us to detect single nucleotide polymorphisms (SNPs). With the aid of
      reverse micelles, a model 40-mer oligonucleotide containing a single-base
      substitution was clearly distinguished from the normal, complementary
      oligonucleotide. In addition, we extended this technique to a high-throughput
      analysis. The results obtained with a 96-well micro-plate reader indicated the
      possibility of SNPs detection toward multiple samples of patients.

PMID- 15566159
TI  - Voltammetric study of interfacial electron transfer between
      bis(cyclopentadienyl)iron in organic solvents and hexacyanoferrate in water.
AB  - The electron-transfer reaction between bis(cyclopentadienyl)iron(II)
      ([Fe(II)(C5H5)2]) in nitrobenzene and a hexacyanoferrate redox couple
      ([Fe(II/III)(CN)6](4-/3-)) in water at the nitrobenzene / water interface was
      studied using normal pulse voltammetry. The voltammetric results indicate that
      the electron-transfer reaction takes place by way of a so-called ion-transfer
      (IT) mechanism, of which the forward and backward rate constants of the
      homogeneous electron-transfer reaction between [Fe(II/III)(C5H5)2](0/+) and
      [Fe(II/III)(CN)6](4-/3-) in the water phase have been determined. The electron
      transfer reaction between [Fe(II)(C5H5)2] in 1,2-dichloroethane and
      [Fe(II/III)(CN)6](4-/3-) in water at the 1,2-dichloroethane / water interface was
      shown to also take place by the IT-mechanism.

PMID- 15566160
TI  - The construction of reality or the deconstruction of the self.

PMID- 15566161
TI  - Martin F. Ward, RMN, DN, Cert. Ed., RNT, MPhil.

PMID- 15566162
TI  - The lived experience of cognitive impairment.

PMID- 15566163
TI  - A meaningful entrance: photo therapy as a psychotherapuetic intervention.
AB  - Photo therapy is a technique that mental health clinicians can use to motivate
      therapeutic discussions with clients. The explicit focus is on the photograph
      rather than on the client; this provides a feeling of emotional safety. Images
      stimulate clients to project their own interpretations. A picture, used as a
      therapeutic process tool, provides a meaningful entrance into an undefended side
      door of the mind to allow for emotional healing.

PMID- 15566164
TI  - Patient & staff satisfaction with integrated services at Old Town Clinic: a
      descriptive analysis.
AB  - This quality improvement project provided a descriptive analysis of the patient
      population that received integrated mental and physical health care at Old Town
      Clinic, and evaluated patient and staff satisfaction with this model of care.
      Seventy-three patients and seven staff members were surveyed, using two
      satisfaction surveys distributed in January 2003. Survey data revealed that the
      majority of Old Town Clinic patients were homeless. Patients indicated high
      levels of satisfaction with the clinic's location, ease of accessing care, and
      health promotion and illness prevention education. Staff satisfaction with this
      model of care was reported to be moderate regarding accessibility, response time,
      communication, support, treatment, completeness of care, and education.
      Recommendations for further research and implications for practice are offered.

PMID- 15566165
TI  - Historical interpretations of alcohol use and misuse. implications for nursing
      curricula.
AB  - Since the 1950's, nursing schools have been encouraged to include some formal
      content on alcoholism in their curricula. Yet there remains on immerse disparity
      between the prevalence of drug and alcohol problems in our society and the
      required number of hour on these topics in our nursing curricula. The
      International Nurses Society on Addictions calls on the nursing profession to
      promote healthy lifestyles for "at-risk" individuals. In a historical context,
      this article critiques the ambivalence related to alcohol use and misuse in the
      United States. Within that background, pedagogy to help nursing faculty and
      students meet current societal and professional demands and standards regarding
      intervention for alcohol-related problems will be explored. The constructivist
      educational and caring-educative models are highlighted.

PMID- 15566166
TI  - Hyperpolarized xenon in NMR and MRI.
AB  - Hyperpolarized gases have found a steadily increasing range of applications in
      nuclear magnetic resonance (NMR) and NMR imaging (MRI). They can be regarded as a
      new class of MR contrast agent or as a way of greatly enhancing the temporal
      resolution of the measurement of processes relevant to areas as diverse as
      materials science and biomedicine. We concentrate on the properties and
      applications of hyperpolarized xenon. This review discusses the physics of
      producing hyperpolarization, the NMR-relevant properties of 129Xe, specific MRI
      methods for hyperpolarized gases, applications of xenon to biology and medicine,
      polarization transfer to other nuclear species and low-field imaging.

PMID- 15566167
TI  - A novel needle-based miniature x-ray generating system.
AB  - The basic concept, design and performance of a novel needle-based x-ray system
      for medical applications are reported. The main principle of the system is based
      on a two-stage production of x-rays. The system comprises a conventional x-ray
      tube with an Ag anode, any known type of conditioning optics and a 2.2 mm
      diameter hollow needle with an interchangeable Mo target. The target can be moved
      along the needle axis and rotated around the needle axis. The needle x-ray device
      allows for adjustment in energy and flux intensity of the x-rays emitted by the
      target. The depth dependence of the intensity, dose rate as well as spatial and
      energy distribution of the radiation emitted by the target have been
      experimentally measured. The depth dose rate results have been compared with
      theoretical calculations using a Monte Carlo simulation of the x-ray production
      process. These studies have experimentally confirmed that the concept of this x
      ray system is correct. Further improvement of the device can increase the dose
      rate up to the levels required for clinical applications.

PMID- 15566168
TI  - A practical method to calculate head scatter factors in wedged rectangular and
      irregular MLC shaped beams for external and internal wedges.
AB  - Factor based methods for absorbed dose or monitor unit calculations are often
      based on separate data sets for open and wedged beams. The determination of basic
      beam parameters can be rather time consuming, unless equivalent square methods
      are applied. When considering irregular wedged beams shaped with a multileaf
      collimator, parametrization methods for dosimetric quantities, e.g. output ratios
      or wedge factors as a function of field size and shape, become even more
      important. A practical method is presented to derive wedged output ratios in air
      (S(c,w)) for any rectangular field and for any irregular MLC shaped beam. This
      method was based on open field output ratios in air (S(c)) for a field with the
      same collimator setting, and a relation f(w) between S(c,w) and S(c). The
      relation f(w) can be determined from measured output ratios in air for a few open
      and wedged fields including the maximum wedged field size. The function f(w) and
      its parametrization were dependent on wedge angle and treatment head design, i.e.
      they were different for internal and external wedges. The proposed method was
      tested for rectangular wedged fields on three accelerators with internal wedges
      (GE, Elekta, BBC) and two accelerators with external wedges (Varian). For
      symmetric regular beams the average deviation between calculated and measured
      S(c,w) / S(c) ratios was 0.3% for external wedges and about 0.6% for internal
      wedges. Maximum deviations of 1.8% were obtained for elongated rectangular fields
      on the GE and ELEKTA linacs with an internal wedge. The same accuracy was
      achieved for irregular MLC shaped wedged beams on the accelerators with MLC and
      internal wedges (GE and Elekta), with an average deviation < 1% for the fields
      tested. The proposed method to determine output ratios in air for wedged beams
      from output ratios of open beams, combined with equivalent square approaches, can
      be easily integrated in empirical or semi-empirical methods for monitor unit
      calculations.

PMID- 15566169
TI  - Electron paramagnetic resonance (EPR) dosimetry using lithium formate in
      radiotherapy: comparison with thermoluminescence (TL) dosimetry using lithium
      fluoride rods.
AB  - Solid-state radiation dosimetry by electron paramagnetic resonance (EPR)
      spectroscopy and thermoluminescence (TL) was utilized for the determination of
      absorbed doses in the range of 0.5-2.5 Gy. The dosimeter materials used were
      lithium formate and lithium fluoride (TLD-100 rods) for EPR dosimetry and TL
      dosimetry, respectively. 60Co gamma-rays and 4, 6, 10 and 15 MV x-rays were
      employed. The main objectives were to compare the variation in dosimeter reading
      of the respective dosimetry systems and to determine the photon energy dependence
      of the two dosimeter materials. The EPR dosimeter sensitivity was constant over
      the dose range in question, while the TL sensitivity increased by more than 5%
      from 0.5 to 2.5 Gy, thus displaying a supralinear dose response. The average
      relative standard deviation in the dosimeter reading per dose was 3.0% and 1.2%
      for the EPR and TL procedures, respectively. For EPR dosimeters, the relative
      standard deviation declined significantly from 4.3% to 1.1% over the dose range
      in question. The dose-to-water energy response for the megavoltage x-ray beams
      relative to 60Co gamma-rays was in the range of 0.990-0.979 and 0.984-0.962 for
      lithium formate and lithium fluoride, respectively. The results show that EPR
      dosimetry with lithium formate provides dose estimates with a precision
      comparable to that of TL dosimetry (using lithium fluoride) for doses above 2 Gy,
      and that lithium formate is slightly less dependent on megavoltage photon beam
      energy than lithium fluoride.

PMID- 15566170
TI  - Noise reduction and convergence of Bayesian algorithms with blobs based on the
      Huber function and median root prior.
AB  - Iterative image reconstruction algorithms have the potential to produce low noise
      images. Early stopping of the iteration process is problematic because some
      features of the image may converge slowly. On the other hand, there may be noise
      build-up with increased number of iterations. Therefore, we examined the
      stabilizing effect of using two different prior functions as well as image
      representation by blobs so that the number of iterations could be increased
      without noise build-up. Reconstruction was performed of simulated phantoms and of
      real data acquired by positron emission tomography. Image quality measures were
      calculated for images reconstructed with or without priors. Both priors
      stabilized the iteration process. The first prior based on the Huber function
      reduced the noise without significant loss of contrast recovery of small spots,
      but the drawback of the method was the difficulty in finding optimal values of
      two free parameters. The second method based on a median root prior has only one
      Bayesian parameter which was easy to set, but it should be taken into account
      that the image resolution while using that prior has to be chosen sufficiently
      high not to cause the complete removal of small spots. In conclusion, the Huber
      penalty function gives accurate and low noise images, but it may be difficult to
      determine the parameters. The median root prior method is not quite as accurate
      but may be used if image resolution is increased.

PMID- 15566171
TI  - LOR-OSEM: statistical PET reconstruction from raw line-of-response histograms.
AB  - Iterative statistical reconstruction methods are becoming the standard in
      positron emission tomography (PET). Conventional maximum-likelihood expectation
      maximization (MLEM) and ordered-subsets (OSEM) algorithms act on data which have
      been pre-processed into corrected, evenly-spaced histograms; however, such pre
      processing corrupts the Poisson statistics. Recent advances have incorporated
      attenuation, scatter and randoms compensation into the iterative reconstruction.
      The objective of this work was to incorporate the remaining pre-processing steps,
      including arc correction, to reconstruct directly from raw unevenly-spaced line
      of-response (LOR) histograms. This exactly preserves Poisson statistics and full
      spatial information in a manner closely related to listmode ML, making full use
      of the ML statistical model. The LOR-OSEM algorithm was implemented using a
      rotation-based projector which maps directly to the unevenly-spaced LOR grid.
      Simulation and phantom experiments were performed to characterize resolution,
      contrast and noise properties for 2D PET. LOR-OSEM provided a beneficial noise
      resolution tradeoff, outperforming AW-OSEM by about the same margin that AW-OSEM
      outperformed pre-corrected OSEM. The relationship between LOR-ML and listmode ML
      algorithms was explored, and implementation differences are discussed. LOR-OSEM
      is a viable alternative to AW-OSEM for histogram-based reconstruction with
      improved spatial resolution and noise properties.

PMID- 15566172
TI  - Photoacoustic determination of blood vessel diameter.
AB  - A double-ring sensor was applied in photoacoustic tomographic imaging of
      artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to
      peak time (tau(pp)) of the laser (1064 nm) induced pressure transient was used to
      estimate the axial vessel diameter. Comparison with the actual vessel diameter
      showed that the diameter could be approximated by 2ctau(pp), with c the speed of
      sound in blood. Using this relation, the lateral diameter could also precisely be
      determined. In vivo imaging and monitoring of changes in vessel diameters was
      feasible. Finally, acoustic time traces were recorded while flushing a vessel in
      the rabbit ear with saline, which proved that the main contribution to the laser
      induced pressure transient is caused by blood inside the vessel and that the
      vessel wall gives only a minor contribution.

PMID- 15566173
TI  - Photonic crystal fibre enables short-wavelength two-photon laser scanning
      fluorescence microscopy with fura-2.
AB  - We report on a novel and compact reliable laser source capable of short
      wavelength two-photon laser scanning fluorescence microscopy based on soliton
      self-frequency shift effects in photonic crystal fibre. We demonstrate the
      function of the system by performing two-photon microscopy of smooth muscle cells
      and cardiac myocytes from the rat pulmonary vein and Chinese hamster ovary cells
      loaded with the fluorescent calcium indicator fura-2/AM.

PMID- 15566174
TI  - Equipotential projection-based magnetic resonance electrical impedance tomography
      and experimental realization.
AB  - In this study, a direct, fast image reconstruction algorithm, based on the fact
      that equipotential lines are perpendicular to current lines in a volume
      conductor, is proposed for magnetic resonance electrical impedance tomography (MR
      EIT). The proposed technique is evaluated both on simulated and measured data for
      conductor and insulator objects.

PMID- 15566175
TI  - A modelling error approach for the estimation of optical absorption in the
      presence of anisotropies.
AB  - Optical tomography is an emerging method for non-invasive imaging of human
      tissues using near-infrared light. Generally, the tissue is assumed isotropic,
      but this may not always be true. In this paper, we present a method for the
      estimation of optical absorption coefficient allowing the background to be
      anisotropic. To solve the forward problem, we model the light propagation in
      tissue using an anisotropic diffusion equation. The inverse problem consists of
      the estimation of the absorption coefficient based on boundary measurements.
      Generally, the background anisotropy cannot be assumed to be known. We treat the
      uncertainties in the background anisotropy parameter values as modelling error,
      and include this in our model and reconstruction. We present numerical examples
      based on simulated data. For reference, examples using an isotropic inversion
      scheme are also included. The estimates are qualitatively different for the two
      methods.

PMID- 15566176
TI  - An investigation on the use of data-driven scattering profiles in Monte Carlo
      simulations of ultraviolet light propagation in skin tissues.
AB  - Ultraviolet light can affect the appearance and medical condition of the human
      skin by triggering biophysical processes such as erythema, melanogenesis,
      photoaging and carcinogenesis. The evolution of these processes is related to the
      amount of ultraviolet light absorbed by skin pigments. This amount may vary with
      the wavelength and path length of the radiation that is propagated within the
      skin tissues. For many years, biomedical researchers have been investigating the
      propagation of ultraviolet light in skin tissues through Monte Carlo simulations.
      The scattering of the incident radiation by tissue internal structures, a key
      component in this process, is usually approximated by functions without a
      plausible connection with the underlying physical phenomena. In this paper, we
      examine the origins of such an approach, and question its generalized use with
      respect to wavelengths and biological materials for which there is no supporting
      data available. Furthermore, we perform comparisons to demonstrate that the
      accuracy and predictability of Monte Carlo simulations of ultraviolet propagation
      in skin tissues can be improved by using a data-driven approach to represent the
      scattering profile of these tissues.

PMID- 15566177
TI  - Hypofractionation in non-small cell lung cancer (NSCLC): suggestions from
      modelling both acute and chronic hypoxia.
AB  - Based on experimental estimates for acute and chronic tumour hypoxia, a
      speculative analysis of the therapeutic ratio dependence on the number of once
      daily five-days-per-week fractions (n) for non-small cell lung cancer (NSCLC)
      radiotherapy is proposed. For this purpose an adapted formulation of the linear
      quadratic model has been derived, including the effects of tumour repopulation,
      inter-tumour alpha-heterogeneity and oxygen enhancement ratio dependence on the
      dose per fraction. The relation between the curative dose D50, assuring 50%
      tumour control probability, and n has been computed: for (n, D50) fractionation
      schemes, the therapeutic ratios have been compared in terms of effective
      normalized total doses to the lungs (NTD(eff)L), estimated by a few supposed
      fractions of the normalized total dose to the tumour. Results suggest that D50 is
      dominated by chronic hypoxia for shortly hypofractionated treatments and by acute
      hypoxia for multifractionated treatments. Furthermore, the optimum number of
      fractions depends on the rapidity of the reoxygenation from chronically hypoxic
      cells, almost independently of the extent of both chronic and acute hypoxia. For
      NSCLC, both the reduction of n until about 20 fractions in hypofractionated dose
      escalation trials, and the extension of extra-cranial stereotactic radiotherapy
      schedules to include at least 5-10 fractions, seem to be supported by this model.

PMID- 15566178
TI  - Extending the linear-quadratic model for large fraction doses pertinent to
      stereotactic radiotherapy.
AB  - Ongoing clinical trials designed to explore the use of extracranial stereotactic
      radiosurgery (ESR) for different tumour sites use large doses per fraction (15,
      20, 30 Gy or even larger). The question of whether the linear-quadratic (LQ)
      model is appropriate to describe radiation response for such large fraction doses
      has been raised and has not been answered definitively. It has been proposed that
      mechanism-based models, such as the lethal-potentially lethal (LPL) model, could
      be more appropriate for such large fraction/acute doses. However, such models are
      not well characterized with clinical data and they are generally not easy to use.
      The purpose of this work is to modify the LQ model to more accurately describe
      radiation response for high fraction/acute doses. A new parameter is introduced
      in the modified LQ (MLQ) model. The new parameter introduced is characterized
      based both on in vitro cell survival data of several human tumour cell lines and
      in vivo animal iso-effect curves. The MLQ model produces a better fit to the iso
      effect data than the LQ model. For a high single dose irradiation, the prediction
      of the MLQ is consistent with that from the LPL model. Unlike the LPL model, the
      MLQ model retains the simplicity of the LQ model and uses the well-characterized
      alpha and beta parameters. This work indicates that the standard LQ model can
      lead to erroneous results when used to calculate iso-effects with large fraction
      doses, such as those used for ESR. We present a solution to this problem.

PMID- 15566179
TI  - Experimental study of attenuation properties of normoxic polymer gel dosimeters.
AB  - The change in linear attenuation coefficient with absorbed dose has been
      investigated for aqueous polyacrylamide, gelatine and tetrakis (PAGAT) and
      aqueous methacrylic acid, gelatine and tetrakis (MAGAT) normoxic polymer gel
      dosimeters using tetrakis (hydroxy methyl) phosphonium chloride as the
      antioxidant. The measured linear attenuation coefficient increased linearly with
      absorbed dose up to 15 Gy for PAGAT gels and 10 Gy for MAGAT gels. Computerized
      tomography (CT) numbers or Hounsfield units (H) were calculated from the linear
      attenuation coefficients and compared with values obtained using a CT scanner.
      Both calculated and measured CT numbers followed a similar pattern when fitted
      with a biexponential curve. The CT numbers obtained from linear attenuation
      measurements were found to be greater than that obtained with the CT scanner for
      both PAGAT and MAGAT polymer gels. The H-dose sensitivities of the MAGAT and
      PAGAT polymer gel dosimeters measured on a CT scanner were calculated to be (0.85
      +/- 0.08) H Gy(-1) and (0.31 +/- 0.03) H Gy(-1), respectively. The H-dose
      sensitivities of the MAGAT and PAGAT polymer gel dosimeters from attenuation
      measurements were found to be (1.10 +/- 0.66) H Gy(-1) and (0.34 +/- 0.01) H Gy(
      1), respectively.

PMID- 15566180
TI  - Quantification of amoA gene abundance and their amoA mRNA levels in activated
      sludge by real-time PCR.
AB  - The transcription level of amoA mRNA encoding a subunit of ammonia monooxygenase
      (AMO) in ammonia-oxidizing bacteria (AOB) was quantified by reverse transcription
      polymerase chain reaction (RT-PCR) methods in combination with real-time PCR
      technology. The effects of ammonia concentration and dissolved oxygen (DO) on the
      transcription levels of amoA mRNA and 16S rRNA in AOB were evaluated in batch
      experiments with nitrifying sludge taken from a lab-scale reactor treating
      artificial wastewater. A batch incubation without ammonia resulted in a rapid
      decrease, within four hours, in the transcription level of amoA mRNA to as low as
      1/10 of that at the beginning of the experiment, while the 16S rRNA level in AOB
      was almost constant. After subsequent incubation with 3 mM ammonia for eight
      hours, a small increase in the transcription level of amoA mRNA occurred, but
      ammonia oxidation proceeded in the interim. Copy numbers of amoA mRNA showed an
      almost fixed value for over eight hours in the absence of dissolved oxygen.

PMID- 15566181
TI  - Distribution of ammonia-oxidizing bacteria in sewage activated sludge: analysis
      based on 16S rDNA sequence.
AB  - This study carried out analysis of ammonia-oxidizing bacteria (AOB) communities
      in 12 sewage activated sludge systems standing in eight sewage treatment plants
      located in Tokyo. The systems were different in the treatment process
      configuration: anaerobic/anoxic/aerobic (A20), anaerobic/aerobic (AO), and
      conventional activated sludge (AS) processes. AOB communities were analyzed by
      sequences of 16S rDNA amplicons, which were separated by denaturing gradient gel
      eletrophoresis (DGGE) after specific polymerase chain reaction (PCR)
      amplification. The results demonstrated that low ammonium concentrations in the
      influents of the 12 sewage activated sludge systems resulted in the dominance of
      Nitrosomonas oligotropha-like sequences. Further, Nitrosomonas europaea- and
      Nitrosomonas cryotolerans-like sequences were recovered from only one A20 system
      of which the influent contained higher ammonium and chloride concentrations than
      those of other systems. Nitrosomonas communis-like sequences were found in every
      A20 and AO system, but mostly not found in every AS system. In summary, influent
      characteristics and treatment process configuration affected the AOB communities
      in the 12 sewage activated sludge systems.

PMID- 15566182
TI  - Comparison of aerobic denitrifying activity among three cultural species with
      various carbon sources.
AB  - Abilities of three aerobic denitrifiers such as Alcaligenes faecalis,
      Microvirgula aerodenitrificans and Paracoccus pantotrophus were compared from the
      viewpoints of nitrate removal efficiency and organic matter utilization. First,
      the effect of carbon source was investigated. Although nitrate reduction was
      observed in all strains under aerobic conditions, a change of carbon source
      considerably affected the denitrification ability. In the case of P.
      pantotrophus, nitrate and nitrite were completely removed in three days under
      sodium acetate or leucine as a carbon source. In the case of A. faecalis,
      sufficient nitrate removal was observed only when sodium acetate or ethanol was
      added. P. pantotrophus and A. faecalis showed a higher ability of nitrate removal
      than that of M. aerodenitrificans. Therefore, P. pantotrophus was selected in
      order to investigate the effects of concentration and repetitive addition of
      carbon. Sodium acetate was used as a sole carbon source. Nitrate was not reduced
      when the carbon concentration was below 500 mgC/L. However, when carbon source
      was added repeatedly, nitrate was reduced under 100 mgC/L after the optical
      density of the bacterium reached above 1.0. This result indicated that a high
      enough level of bacterial density was necessary to express aerobic
      denitrification activity.

PMID- 15566183
TI  - Arsenic removal from groundwater by a newly developed adsorbent.
AB  - A novel adsorbent, which had been developed for phosphate adsorption, was adopted
      for arsenic removal from groundwater. Adsorption isotherm, pH dependence of the
      isotherm and adsorption rate were studied by batch method. Furthermore, by using
      a granular adsorbent of 1.8 mm diameter which is commercially available, lab
      scale experiments of continuous adsorption treatment of actual groundwater
      containing arsenic at 50 mg m(-3) were conducted to examine the performance of
      the adsorbent. A large amount of arsenic, i.e., 10 g As kg(-1), was adsorbed at
      pH 7.0 and 10 mg As m(-3) in equilibrium concentration. It was only a 5% higher
      amount compared to conventional activated alumina. However, twice the bed volume,
      i.e., total volume of effluent divided by empty column volume, was achieved till
      breakthrough by using this novel adsorbent. This may be because the pH decrease,
      which enlarges apparent adsorption capacity of the adsorbent, is caused by a self
      pH decrease function of the adsorbent. The self-pH decrease function must be
      delivered by dissociation of Al (III) aquoion. The proton release was clearly
      observed in batch experiments.

PMID- 15566184
TI  - Improvement of denitrification by denitrifying phosphorus removing bacteria using
      sequentially combined carbon.
AB  - The effects of sequentially combined carbon (SCC) using a symbiotic relationship
      of methanol and acetic acid on biological nutrient removal were investigated in
      both the continuous bench scale process consisting of an anoxic, an aerobic and a
      final settling tank and intensive batch tests. Compared to the use of respective
      sole carbon sources, methanol and acetic acid, the use of SCC showed superior
      removal efficiency of nitrogen (98.3%) and phosphorus (approximately 100%).
      Furthermore, the use of SCC enhanced simultaneous denitrification and phosphorus
      uptake by denitrifying phosphorus removal bacteria (DPB), resulting in the
      highest specific denitrification rate (SDNR) of 0.252 g NO3-N/g VSS/d achieved
      from the first anoxic zone with methanol of 30 mg COD/I. From batch tests
      performed under carbon limited anoxic conditions, 1 g of nitrate was used by DPB
      for P-uptake of 1.19 g. According to this result, 0.205 g NO3-N/g VSS/d was
      accomplished by normal denitrifiers using methanol, and 0.047 g NO3-N/g VSS/d was
      achieved by DPB. This research also demonstrated that the increase of poly-beta
      hydroxybutyrate (PHB) stored by phosphorus accumulating organisms (PAOs) could be
      of importance in improving aerobic denitrification. The use of SCC produced the
      highest P-release in the anoxic zone, indicating the amount of PHB would be
      higher compared to the use of other sole carbons. Therefore, the SCC could be a
      very effective carbon source for the enhancement of aerobic denitrification as
      well.

PMID- 15566185
TI  - In-situ characterization of microbial community in an A/O submerged membrane
      bioreactor with nitrogen removal.
AB  - The bacterial community involved in removing nitrogen from sewage and their
      preferred DO environment within an anoxic/oxic membrane bioreactor (A/O MBR) was
      investigated. A continuously operated laboratory-scale A/O MBR was maintained for
      360 d. At a sludge age of 150 d and a C/N ratio of 3.5, the system was capable of
      removing 88% of the influent nitrogen from raw wastewater through typical
      nitrogen removal transformations (i.e. aerobic ammonia oxidation and anoxic
      nitrate reduction). Characterization of the A/O MBR bacterial community was
      carried out using fluorescence in situ hybridization (FISH) techniques. FISH
      results further showed that Nitrosospira spp. and Nitrospira spp. were the
      predominant groups of ammonia and nitrite oxidizing group, respectively. They
      constituted up to 11% and 6% of eubacteria at DO below 0.05 mg/l (low DO),
      respectively, and about 14% and 9% of eubacteria at DO between 2-5 mg/l
      (sufficient DO), respectively, indicating preference of nitrifiers for a higher
      DO environment. Generally low counts of the genus Paracoccus were detected while
      negative results were observed for Paracoccus denitrificans, Alcaligenes spp, and
      Pseudomonas stutzeri under the low and sufficient DO environments. The overall
      results indicate that Nitrosospira spp., Nitrospira spp. and members of
      Paracoccus spp. can be metabolically functional in nitrogen removal in the
      laboratory-scale A/O MBR system.

PMID- 15566186
TI  - The effect of divalent metal ions on the zeta potential of bubbles.
AB  - Micro-bubbles are used in electro-flotation (EF) and dissolved air flotation
      (DAF) for particle separation. The efficiency of these flotation processes
      depends on the collision of bubble and particle and the collision efficiency is
      affected by certain parameters with respect to the size and zeta potential of
      bubble and particle. Therefore, it is necessary to monitor not only the zeta
      potential of the particle, but also that of the bubble. Gas bubbles are reported
      to be generally negatively charged in water. In this paper, we report a study
      performed to measure the zeta potential of bubbles in solutions containing
      divalent metals and find factors which can produce positively charged bubbles.
      Calcium and magnesium ions were selected as divalent metal ions because natural
      water normally contains an appreciable quantity of them. It was found that
      bubbles are negatively charged in CaCl2 solutions whereas, under certain
      conditions, they become positively charged in MgCl2. Charge reversal of bubbles
      was observed above 10(-2) M Mg, especially above pH 9. A probable principle that
      explained the charge reversal could be a combined mechanism with both specific
      adsorption of hydroxylated species and formation of hydroxide precipitates.
      Creating solution conditions that can produce positively charged bubbles in
      flotation methods might make it possible to remove particles using lesser amounts
      of coagulant or even none at all.

PMID- 15566187
TI  - Monitoring of COD as an organic indicator in waste water and treated effluent by
      fluorescence excitation-emission (FEEM) matrix characterization.
AB  - The fluorescence excitation-emission matrices (FEEM) of domestic waste water,
      treated effluent of a waste water treatment plant and receiving river water were
      analyzed to select wavelengths for the monitoring of organic contents as COD.
      Excitation/emission wavelengths of 220/350 nm and 270/350 nm for protein-like
      fluorescence and 240/450 nm and 340/450 nm for humic-like fluorescence were
      suggested as fluorescence peak emitting wavelength pairs, respectively. Without
      any pre-treatment, the protein-like fluorescence peaks showed better correlation
      between COD values and fluorescence intensities than the humic-like fluorescence
      peaks. No enhanced correlation was observed by removing the suspended solids from
      the samples using filtration. However, statistical multiple regression methods,
      using the fluorescence intensities from each peak and the light scattering
      intensity at 633 nm as variables, resulted in an enhanced correlation, with r2 >
      0.9 for the measured and predicted COD values.

PMID- 15566188
TI  - Optimising the performance of a lab-scale tidal flow reed bed system treating
      agricultural wastewater.
AB  - A gravel-based tidal flow reed bed system was operated with three different
      strategies in order to investigate its optimal performance for the treatment of a
      high strength agricultural wastewater. According to the three strategies,
      individual reed beds were saturated and unsaturated with the wastewater for
      different periods while reasonably stable hydraulic and organic loadings were
      maintained. Experimental results demonstrated that the system produced the
      highest pollutant removal efficiencies with a relatively short saturated period
      and long unsaturated period, highlighting the importance of oxygen transfer into
      reed bed matrices during the treatment. Significant removals of some major
      organic and inorganic pollutants were achieved under all three operational
      conditions. Nitrification was not the major route of ammoniacal-nitrogen removal
      when the system was under high organic loading. Due to the filtration of
      suspended solids and the accumulation of biomass, gradual clogging of the reed
      bed matrices took place, which caused concerns over the long-term efficiency of
      the tidal flow system.

PMID- 15566189
TI  - Removal of bromate and assimilable organic carbon from drinking water using
      granular activated carbon.
AB  - This study investigated the feasibility of using granular activated carbon (GAC)
      to remove bromate ion (BrO3-) and assimilable organic carbon (AOC) from drinking
      water through a rapid small-scale column test (RSSCT) method and a pilot-scale
      study. Results from RSSCT indicated that the GAC capacity for BrO3- removal was
      dependent on the GAC type, empty bed contact time (EBCT), and source water
      quality. The GAC with a high number of basic groups and higher pHpzc values
      showed an increased BrO3- removal capacity. BrO3- removal was improved by
      increasing EBCT. The high EBCT provides a greater opportunity for BrO3- to be
      adsorbed and reduced to Br- on the GAC surface. On the other hand, the presence
      of dissolved organic carbon (DOC) and anions, such as chloride, bromide, and
      sulfate, resulted in poor BrO3- reduction. In the GAC pilot plant, a GAC column
      preloaded for 12 months achieved a BrO3- and AOC removal range from 79-96% and 41
      75%, respectively. The BrO3- amount removed was found to be proportional to the
      influent BrO3- concentration. However, the BrO3- removal rate apparently
      decreased with increasing operation time. In contrast, the AOC apparently
      increased during the long-term operation period. This may be a result of the
      contribution due to new GAC being gradually transformed into biological activated
      carbon (BAC), and the bacterial biomass adsorbed on GAC surface hindering BrO3-
      reduction by GAC either by blocking pores or adsorbing at the activated sites for
      BrO3- reduction.

PMID- 15566190
TI  - Long term operation of high concentration powdered activated carbon membrane bio
      reactor for advanced water treatment.
AB  - A pilot scale experiment was conducted to evaluate the performance of a membrane
      bioreactor filled with high concentration powdered activated carbon. This hybrid
      system has great potential to substitute for existing GAC or O3/BAC processes in
      the drinking water treatment train. The system was installed at a water treatment
      plant located downstream of the Nakdong river basin, Korea. Effluent of rapid
      sand filter was used as influent of the system which consists of PAC bio-reactor,
      submerged MF membrane module and air supply facility. PAC concentration of 20 g/L
      was maintained at the beginning of the experiment and it was increased to 40 g/L.
      The PAC has not been changed during the operational periods. The membrane was a
      hollow fiber type with pore sizes of 0.1 and 0.4 microm. It was apparent that the
      high PAC concentration could prevent membrane fouling. 40 g/L PAC was more
      effective to reduce the filtration resistance than 20 g/L. At the flux of 0.36
      m/d, TMP was maintained less than 40 kPa for about 3 months by intermittent
      suction type operation (12 min suction/3 min idling). Adsorption was the dominant
      role to remove DOC at the initial operational period. However the biological
      effect was gradually increased after around 3 months operation. Constant DOC
      removal could be maintained at about 40% without any trouble and then a
      tremendous reduction of DBPs (HAA5 and THM) higher than 85% was achieved. Full
      nitrification was observed at the controlled influent ammonia nitrogen
      concentration of 3 and 7 mg/L. pH was an important parameter to keep stable
      ammonia oxidation. From almost two years of operation, it is clear that the PAC
      membrane bioreactor is highly applicable for advanced water treatment under the
      recent situation of more stringent DBPs regulation in Korea.

PMID- 15566191
TI  - Coupled reduction of chlorinated hydrocarbons and heavy metals by zerovalent
      silicon.
AB  - The feasibility of using zerovalent silicon (Si0) as a novel reductant to remove
      chlorinated compounds and heavy metals in contaminated sites was investigated.
      The kinetics and degradation mechanism of carbon tetrachloride (CT) by Si0 were
      also examined. Results showed that zerovalent silicon could effectively
      dechlorinate the chlorinated compounds. A nearly complete dechlorination of CT by
      Si0 was obtained within 14 h. The produced concentrations of chloroform (CF)
      accounted for 71-88% loss of CT, showing that reductive dechlorination is the
      major degradation pathway for the degradation of chlorinated hydrocarbons by Si0.
      The degradation followed pseudo first-order kinetics and the normalized surface
      reaction rate constant (k(sa)) for CT dechlorination ranged between 0.0342 and
      0.0454 L m(-2) h(-1) when CT concentrations were in the range of 3-20 microM. A
      linear relationship between the k(sa) and pH value was also established. In
      addition, zerovalent silicon has a high capability in the removal of heavy
      metals. 83% of Cr(VI) was removed by 0.5g Si0 within 5 h, which is higher than
      that by Fe0. The removal efficiency of divalent metal ions by Si0 followed the
      order of Cu(II) > Pb(II) > Ni(II). This indicates that zerovalent silicon is an
      alternative reductant and can undergo coupled reduction of heavy metals and
      chlorinated hydrocarbons in contaminated groundwater.

PMID- 15566192
TI  - A kinetic study of enhancing effect by phenolic compounds on the hydroxyl radical
      generation during ozonation.
AB  - Ozone decomposition in aqueous solution proceeds through a radical type chain
      mechanism. These reactions involve the very reactive and catalytic intermediates
      O2- radical, OH radical, HO2 radical, OH-, H2O2, etc. OH radical is proposed as
      an important factor in the ozonation of water among them. In the present study,
      the enhancing effects of several phenolic compounds; phenol, 2-, 3-, 4
      monochloro, 2,4-dichloro, 2,4,6-trichlorophenol on OH radical generation were
      mathematically evaluated using the electron spin resonance (ESR)/spin-trapping
      technique. OH radical was trapped with a 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)
      as a stable adduct, DMPO-OH. The initial velocities of DMPO-OH generation in
      ozonated water containing phenolic compounds were quantitatively measured using a
      combined system of ESR spectroscopy with stopped-flow apparatus, which was
      controlled by homemade software. The initial velocities of DMPO-OH generation
      increased as a function of the ozone concentration. The relation among ozone
      concentration, amount of phenolic compounds and the initial velocity (v0) of DMPO
      OH generation was mathematically analyzed and the following equation was
      obtained, v0 (10(-6) M/s) = (A' x [PhOHs (10(-9) M)] + 0.0005) exp (60 x [ozone
      (10(-9) M)]). The equation fitted very well with the experimental results, and
      the correlation coefficient was larger than 0.98.

PMID- 15566193
TI  - KNT-artificial neural network model for flux prediction of ultrafiltration
      membrane producing drinking water.
AB  - This paper describes the prediction of flux behavior in an ultrafiltration (UF)
      membrane system using a Kalman neuro training (KNT) network model. The
      experimental data was obtained from operating a pilot plant of hollow fiber UF
      membrane with groundwater for 7 months. The network was trained using operating
      conditions such as inlet pressure, filtration duration, and feed water quality
      parameters including turbidity, temperature and UV254. Pre-processing of raw data
      allowed the normalized input data to be used in sigmoid activation functions. A
      neural network architecture was structured by modifying the number of hidden
      layers, neurons and learning iterations. The structure of KNT-neural network with
      3 layers and 5 neurons allowed a good prediction of permeate flux by 0.997 of
      correlation coefficient during the learning phase. Also the validity of the
      designed model was evaluated with other experimental data not used during the
      training phase and nonlinear flux behavior was accurately estimated with 0.999 of
      correlation coefficient and a lower error of prediction in the testing phase.
      This good flux prediction can provide preliminary criteria in membrane design and
      set up the proper cleaning cycle in membrane operation. The KNT-artificial neural
      network is also expected to predict the variation of transmembrane pressure
      during filtration cycles and can be applied to automation and control of full
      scale treatment plants.

PMID- 15566194
TI  - Application of a bio-electrochemical reactor process to direct treatment of metal
      pickling wastewater containing heavy metals and high strength nitrate.
AB  - The fundamental performance of a bio-electrochemical reactor for the direct
      treatment of metal pickling wastewater was investigated experimentally. In the
      reactor, carbon anode and cathode were installed. On the cathode, denitrifying
      microorganisms were immobilized. Continuous experiments were carried out by
      feeding a synthetic wastewater containing nitrate and binary heavy metal ions,
      copper and lead, under different operating conditions. Acetate as well as the
      electric current was supplied at the minimum amount for stoichiometry of the
      dissimilatory denitrification reaction. The results indicated that the dissolved
      copper and lead removal, denitrification and neutralization could be achieved
      simultaneously in a single bio-electrochemical reactor. The dissolved heavy
      metals were removed by electrochemical deposition on cathode and by the other
      phenomena such as the formation of insoluble suspensions and the sorption on
      suspended bacterial sludge. Denitrification proceeded effectively with the
      utilization of both added acetate and hydrogen gas generated by electrolysis of
      water. The pH value increased up to around neutral due to the occurrence of
      denitrification in the reactor, although the influent pH was less than 3. The
      removal efficiencies of heavy metals and nitrate increased with increasing the
      current density. The applied electric current was indispensable for sustaining
      the stable treatment in the reactor.

PMID- 15566195
TI  - Sludge thickening performance of mesh filtration process.
AB  - Small-scale wastewater treatment facilities play an important role in improving
      the aquatic environment in many countries. Although sludge treatment is essential
      for overall wastewater treatment, it is difficult for small-scale facilities to
      use mechanical equipment or other facilities. As the first step of the sludge
      treatment, it is important to develop a convenient sludge thickening process for
      small-scale facilities. In this work, we examined the sludge thickening
      performance of a mesh filtration system: the mesh opening sizes of 100-500
      microm, and the sludge (3,000-9,000 mg-SS/L) was obtained from a domestic
      wastewater treatment facility. The filtration was carried out only under the
      hydraulic pressure between the water level and the effluent port connected to the
      mesh filter module. The sludge reduction rates were in the range of 85-95% for 6
      7 h; the initial filtration rate was very high, but the rate decreased with a
      decrease in hydraulic pressure due to the reduction of the water level in the
      vessel. In addition, the effluents (passed through the mesh) contained very low
      SS and could be directly discharged into the environment.

PMID- 15566196
TI  - Effects of phosphorus limitation and temperature on PHA production in activated
      sludge.
AB  - The study was designed to investigate the effects of temperature and phosphorus
      limitation on polyhydroxyalkanoate (PHA) production and storage by activated
      sludge biomass. The two-stage operation approach, i.e. a growth phase followed by
      a nutrient limitation phase, was applied to induce PHA accumulation. The pre
      selected temperatures of 10, 20 and 30 degrees C were investigated under
      phosphorus limitation conditions using three four-litre fully aerobic SBR systems
      operated at an SRT of 10 days with cycle time and HRT of 6 and 10 hours. PHA
      production was greater in the 10 degrees C system than in the 20 degrees C and 30
      degrees C systems but there was little difference between the two higher
      temperatures. The maximum PHA fractions of the sludge were 52, 45 and 47%TSS for
      the three temperatures from low to high, and the maximum PHA concentrations in
      the mixed liquors were 1,491, 1,294 and 1,260 mg/l, respectively. However, it was
      observed that very low values of PHA yield per unit COD consumed were obtained,
      i.e., 0.05, 0.03 and 0.04 mgPHA/mgCODu, for the 10, 20 and 30 degrees C reactors,
      respectively. This was because all three systems required several days to reach
      maximum PHA accumulation in their mixed liquor biomasses. It is probable the
      bacteria still had some stored poly-P in their cells upon initiation of the
      phosphorus limited influent, and PHA accumulation was delayed until the stored
      phosphorus was depleted. Also, PHA productivity was reduced by the large amounts
      of biomass lost from the systems because of sludge bulking.

PMID- 15566197
TI  - Nitrate removal with low N2O emission by application of sulfur denitrification in
      actual agricultural field.
AB  - Sulfur denitrification was applied to the agricultural field and the
      characteristics of the treatment were evaluated from the viewpoints of nitrate
      removal efficiency and nitrous oxide (N2O) emission. Two actual sites where
      sulfur denitrification was performed were surveyed. One is a valley bottom field,
      where groundwater contaminated with nitrate is coming up as spring water. The
      nitrate concentration in influent was about 45 mgN/L. The other was wastewater
      from a plastic greenhouse. The nitrate concentration in inflow water was about
      200 mgN/L. Nitrate was almost removed by the containers packed with sulfur (S0)
      CaCO3 blocks in both sites. Increase of sulfate indicated that nitrate was
      removed by sulfur denitrification. This was also estimated stoichiometrically
      from the relationships between the removed nitrate and produced sulfate. The N2O
      was supersaturated in water at most sampling points and the highest concentration
      of dissolved N2O reached 900 microgN/L in Saitama in March. It seemed that
      insufficient nitrate removal caused accumulation of intermediates during
      denitrification, such as nitrite and N2O, in this month. However, the emission
      ratio of N2O to the removed nitrate during these processes was kept low, ranging
      from 0.01 to 0.19%, at both two sites throughout all surveys.

PMID- 15566198
TI  - Microbial degradation of estrogens using activated sludge and night soil
      composting microorganisms.
AB  - In order to investigate the potential for microbial degradation of estrogens, and
      the products formed, activated sludge collected from Korea (ASK) and night soil
      composting microorganisms (NSCM) were used to degrade estrogens. Results showed
      that both ASK and NSCM degraded almost 100% of the natural estrogens estrone
      (E1), 17beta-estradiol (E2), and estriol (E3) from initial concentrations of 20
      25 mg/L, while synthetic estrogen, ethynylestradiol (EE2), was not degraded.
      Analysis of degradation products of E2 by using HPLC-ECD and a consecutive first
      order reaction calculation confirmed that E2 was sequentially degraded to E1,
      which was further degraded to other unknown compounds by ASK and NSCM. We then
      used the yeast two-hybrid assay to show that the unknown degradation products did
      not appear to possess estrogenic activity when E1, E2 or E3 were degraded to
      below the detection limit after 14 days of incubation, indicating that ASK and
      NSCM not only degrade natural estrogens, but also remove their estrogenic
      activities.

PMID- 15566199
TI  - Enhanced remediation of carbon tetrachloride by Fe(II)-Fe(III) systems in the
      presence of copper ions.
AB  - The effect of Cu(II) ion on the dechlorination of carbon tetrachloride (CT) by
      Fe(II) associated with various iron oxides was investigated. Iron oxides
      including goethite, hematite, ferrihydrite and magnetite were selected as the
      model compounds. CT was dechlorinated to chloroform (CF) by 3 mM Fe(II) in iron
      oxide suspensions at pH 7.2. The dechlorination followed pseudo first-order
      kinetics and the pseudo first-order rate constants (k(obs)) were 0.048 h(-1),
      0.0836 h(-1), 0.0609 h(-1) and 0.0144 h(-1) in goethite-, hematite-, ferrihydrite
      and magnetite-amended systems, respectively. Addition of Cu(II) into systems
      increased the k(obs) for CT dechlorination significantly. A 3- to 120-fold
      increase in k(obs) relative to the systems without Cu(II) was observed when 0.5
      mM Cu(II) was added to the Fe(II)-Fe(III) suspensions. The pH of the system is an
      important factor controlling the dechlorination rate of CT. The increase in
      concentrations of Fe(II) and iron oxides also enhanced the dechlorination
      efficiency and rate of CT. Moreover, a linear relationship between the k(obs) and
      Cu(II) concentration ranging between 0 and 0.4 mM was observed. Results obtained
      demonstrate the feasibility of using surface-bound iron species with Cu(III) for
      the detoxification of chlorinated solvents in the contaminated aquifers.

PMID- 15566200
TI  - Optimizing volatile fatty acid production in partial acidogenesis of swine
      wastewater.
AB  - This research has been conducted based on the fact that acetic and butyric acids
      are favorable substrates for methanogens, and that a low level of propionic acid
      production during acidogenesis minimizes the inhibition effect on methanogenic
      growth. Raw swine wastewater was pretreated with ammonia stripping to enhance
      acidogenesis. The ammonia nitrogen concentration of less than 1.2 g/L did not
      significantly affect the biochemical acidogenic potential of swine wastewater.
      For acidogenesis of swine wastewater, a set of experiments were carried out to
      produce short chain volatile fatty acids (VFA) in laboratory-scale continuously
      stirred tank reactors. The production of acetic, propionic, and butyric acids
      associated with simultaneous changes in hydraulic retention time (HRT) and
      temperature was investigated. Response surface methodology was successfully
      applied to approximate the responses of the VFA productions. The optimum
      physiological conditions where the maximum acetic and butyric acids production
      occurred were 2.4 days HRT at 34 degrees C and 2.1 days HRT at 35 degrees C,
      respectively. The propionic acid production linearly increased as both HRT and
      temperature increased.

PMID- 15566201
TI  - Effect of chlorination bulking control on water quality and phosphate
      release/uptake in an anaerobic-oxic activated sludge system.
AB  - This study evaluates the effect of chlorination bulking control on water quality
      and phosphate release/uptake in an anaerobic-oxic activated sludge system. A
      series of batch experiments with different specific NaOCl mass dose were
      conducted to determine the sludge settling properties, supernatant water quality
      and phosphate metabolism behavior of filamentous bulking sludge. The harvested
      sludge was from a continuous-flow anaerobic-oxic (A/O) activated sludge pilot
      plant, i.e., enhanced biological phosphorus removal (EBPR) system, operated with
      15 days of sludge retention time. The filamentous bacteria in the A/O pilot plant
      were identified to be Thiothrix according to Eikelboom's classification
      techniques, which was in accordance with the high influent sulfate concentration
      of this study (50 mg/L sulfate). Increasing NaOCI concentration, as revealed by
      experimental results, obviously decreased the sludge settling properties (SVI
      values and zone settling velocities) and meanwhile significantly reduced
      supernatant water quality (COD, SS, TP) mainly due to higher suspended solids
      caused by floc disruption. Moreover, the nine-hour batch experiments indicated
      that high NaOCI dosage (40 mg/gMLSS) completely deteriorated phosphate metabolism
      of EBPR sludge. Such a high dosage of chlorination further confirmed overdosing
      through disappearance of intracellular PHB and death of protozoa by microscopic
      investigation. Still, phosphate release/uptake behavior of EBPR sludge properly
      functions at low NaOCl dosage (5 mg/g MLSS). Besides, phosphate metabolism
      worsens rapidly before the SVI value reaches its lowest level. These findings
      imply that determining NaOCI requirement with merely SVI values can readily
      result in chlorination overdosing. Proper NaOCI dosage requires a delicately
      balanced consideration between sludge settling improvement, water quality demand
      and phosphate metabolism. Batch test of phosphate release/uptake is apparently a
      prerequisite to conclude an appropriate NaOCl dosage for bulking control.

PMID- 15566202
TI  - Pretreatment of silk-dyeing industrial wastewater by UASB reactor.
AB  - The objective of this study was to investigate the performance of the upflow
      anaerobic sludge blanket (UASB) reactor as the pretreatment system for silk
      dyeing wastewater. Two laboratory-scale UASB reactors, with working volume of
      15.59 I, were used during May 1998 to June 1999. The actual wastewater was
      diluted to reduce ammonium ion toxicity on anaerobic bacteria. The experiments
      were conducted at the organic loading rates (OLRs) of 0.52, 1.01, 1.04, 1.54 and
      2.56 kgCOD/(m3 x d), treating only wastewater generated from the acid-dye process
      of mixed-species raw silk. It took approximately 4 1/2 months to reach the steady
      state conditions. It was found that the COD removal was in the ranges of 74.1
      85.3%, except at OLR 2.56 kgCOD/(m3 x d) where efficiency significantly dropped
      to 55.2%. The apparent color removal was in the similar trend as COD. During the
      study periods, wastewater input had various color shades while the effluent
      generally looked pale yellowish. The methane generation rates ranged from 0.18
      0.31 m3/kg COD removed, with methane composition 81.0-88.1% in biogas. The
      average granule size in the sludge bed had slowly increased to 0.73 mm in the
      last experiment. It can be concluded that the UASB reactor is suitable as a
      pretreatment system for silk-dyeing wastewater. An OLR of 1 kgCOD/(m3 x d) and an
      influent concentration diluted to 2,600 mgCOD/l are suggested while COD and
      apparent color removal efficiency of 80% and 70%, respectively, can be expected.

PMID- 15566203
TI  - High rate treatment by aerobic upflow sludge blanket (AUSB) with external
      oxygenation.
AB  - A 3-year study was conducted using an aerobic upflow sludge blanket (AUSB)
      reactor to achieve high-rate biological treatment through maintenance of a high
      biomass concentration (7-10 g VSS/L) together with a high oxygen flux. The AUSB
      reactor was not aerated directly; instead, oxygenation was provided in an
      external chamber with flow recirculation. The oxygenation was provided at four
      different pressurizations: 0, 15, 20 and 25 psig. The AUSB reactor was also
      pressurized to avoid the flotation of biomass. The flow recirculation rate was
      varied from 400% to 1,500% in order to ensure adequate oxygen supply. It was
      found that the AUSB system was able to handle a volumetric loading of as high as
      10 kg COD/m3-day with a removal efficiency of 92%. Despite a high upflow velocity
      through AUSB, the effluent suspended solid concentration was mostly below 60
      mg/L. The active fraction of biomass in the AUSB sludge was about 3 times higher
      than that of the regular activated sludge. This was indicated by a very high
      specific oxygen uptake rate (SOUR), up to 180-250 mg O2/g VSS-hr. The sludge
      yield in the entire system was only 0.09 to 0.13 g VSS/g COD removed. This was
      mainly caused by additional auto-oxidation of biosolids in the oxygenation
      chamber due to flow recirculation.

PMID- 15566204
TI  - Co-removal of hexavalent chromium through adsorption during copper precipitation.
AB  - A systematic study was conducted to assess the mechanisms involved in the co
      removal of hexavalent chromium during chemical precipitation of divalent copper.
      Batch tests were used to assess the precipitation phenomena in both pure copper
      solutions and also mixed copper-Cr(VI) solutions with progressive addition of
      sodium carbonate to increase pH and induce precipitation. It was found that the
      co-removal of Cr(VI) was caused by two distinct mechanisms: coprecipitation of
      copper with Cr(VI) at pH 5.0 to 5.2, leading to the formation of CuCrO4
      precipitates. Once the fine crystallites of CuCrO4 were formed, the test solution
      became heterogeneous and this accelerated the production of copper-carbonate
      precipitates, mainly in the form of CuCO3 Cu(OH)2, at pH 5.2 to 6.2. The latter
      precipitates were negatively charged at pH below 7.5, and thus they were able to
      adsorb a considerable amount of the remaining chromate ions [HCrO4- and CrO4(2
      )]. The extent of adsorption depended on both pH and surface loading. Besides
      electrostatic attraction, ligand exchange was also found to play some role.
      Maximum adsorption occurred at pH 6.5. When pH was raised to 10.0, approximately
      25-30% of the adsorbed chromium could become desorbed due to a surface charge
      reversal on the adsorbent.

PMID- 15566205
TI  - Effects of substrate components on hydrogen fermentation of multiple substrates.
AB  - As is well known, carbohydrate is the most appropriate organic material for
      hydrogen fermentation, and its hydrogen yield is significantly larger than that
      of protein. The fermentation of protein began with hydrogen production followed
      by hydrogen consumption, which helps overall hydrogen recovery. Both carbohydrate
      and protein are basic components of organic material, and yet carbohydrate is
      known to be a better substrate than protein in terms of hydrogen yield during
      hydrogen fermentation. This study used multiple substrates containing different
      ratios of glucose and peptone as multiple substrates to investigate the roles
      played by carbohydrate and protein in hydrogen fermentation. The experimental
      results demonstrated that suitable ratios of glucose and peptone improved the
      growth of hydrogen producing bacteria. Additionally, a maximum hydrogen yield of
      6.4 mmole-H2/g-COD was obtained from the multiple substrate containing 40%
      peptone and 60% glucose. Most of the produced hydrogen came from fermentation of
      glucose, not peptone. During hydrogen fermentation, the pH dropped by 1.0 and 1.9
      units in 80% and 20% of peptone content in the substrate. Ammonia produced due to
      peptone degradation neutralized the acids produced from hydrogen fermentation.

PMID- 15566206
TI  - Characteristics of granular sludge in a single upflow sludge blanket reactor
      treating high levels of nitrate and simple organic compounds.
AB  - Simultaneous denitrification and methanogenesis were accomplished in a single
      upflow sludge blanket (USB) reactor. More than 99% and 95% of nitrate and
      chemical oxygen demand (COD) removal rates were obtained at a loading of 600 mg
      NO3-N/L x d and 3,300 mg COD/L x d, respectively. The specific denitrification
      rate (SDR) increased as COD/NO3-N ratios decreased. Maximum SDR with acetate
      could reach 1.05 g NO3-N/gVSS x d. Significant sludge flotation was observed at
      the top of the reactor due to the change of microbial composition and the
      formation of hollow granules. Granules became fluffy and buoyant due to the
      growth of denitrifiers. Microscopic examination showed that granules exhibited
      layered structure and they were mainly composed of Methanosarcina sp.,
      Pseudomonas sp., and rod-shaped bacteria.

PMID- 15566207
TI  - The importance of keeping our hand in the scrub role.

PMID- 15566208
TI  - Celebrate our value and dance.

PMID- 15566209
TI  - Invite a risk manager to the OR for Perioperative Nurse Week.

PMID- 15566210
TI  - Perioperative education--perspective from the think tank.
AB  - The AORN Foundation and the National League for Nursing (NLN) cosponsored a think
      tank to address concerns about the shortage of perioperative nurses and the lack
      of perioperative experiences in many nursing programs. Think tank participants
      identified traditional and existing paradigms in nursing education and envisioned
      a new self-directed learning model for nursing school curricula, in which
      students would be held accountable for their own learning and faculty members
      would serve as learning facilitators. AORN and NLN members agreed to collaborate
      to spread the message that the perioperative arena is an excellent place for
      nursing students to develop the knowledge, skills, and values they will need to
      practice effectively in today's complex health care institutions.

PMID- 15566211
TI  - A pragmatic and successful approach to treating nonsmall-cell lung carcinoma.
AB  - Lung cancer is the single leading cause of cancer deaths for men and women
      combined. Nonsmall-cell lung carcinoma (NSCLC), which results largely from
      smoking tobacco, accounts for 87% of all lung cancer cases. Methods of patient
      selection, preoperative and intraoperative care, and postoperative outcomes for
      patients with NSCLC who were treated from 1991 through 2003 at Inova Fairfax
      Hospital are discussed. All patients were treated with surgery, some selectively
      and progressively with a combination of preoperative neoadjuvant therapy, to try
      to downstage the disease to make complete resection feasible. Outcomes from this
      data collection period match or exceed the best results for treatment of late
      stage (ie, III and IV) disease reported anywhere to date.

PMID- 15566212
TI  - Planning for and positioning a solo RN first assistant practice.
AB  - Registered nurse first assistants who go into practice for themselves need to
      construct a budget for the business and determine how the practice will be
      organized by developing a business plan. After a practice is established, it is
      important to position the practice in the marketplace by creating a positive
      image in prospective clients' minds.

PMID- 15566213
TI  - Women's experience with breast biopsy.
AB  - The purpose of this study was to obtain descriptions of the perioperative
      experiences of women who underwent breast biopsies with local anesthesia. Twenty
      two participants were interviewed, and open-ended questions were used to allow
      the women to describe their experiences. Data analysis revealed three major
      themes--certitude, care, and justice. The women's most pervasive need was to have
      the biopsy results as soon as possible. They viewed the surgical phase of the
      biopsy as a stepping-stone to achieving certitude associated with having the
      pathology results. The surgical phase of the biopsy did not hold as much
      significance for the women as the researcher had anticipated.

PMID- 15566214
TI  - Implementing a perioperative nursing elective in a baccalaureate curriculum.
AB  - Perioperative nursing units are experiencing a critical shortage of trained RNs,
      and new nursing school graduates are unlikely to enter this specialty unless they
      have had experience in a perioperative environment during their clinical
      rotations. In cooperation with a local hospital, a school of nursing developed a
      perioperative elective with a clinical component. The perioperative elective has
      received strong support from faculty members and hospital staff members, and
      students believe they have enhanced their individual clinical experience through
      participation in this course.

PMID- 15566215
TI  - From handmaiden to right hand--World War I and advancements in medicine.
AB  - The exigencies created by modern warfare techniques used during World War I led
      to a number of advancements in the medical field. Authorities had to find new
      ways to deal with the overwhelming numbers of wounded and the terrible wounds
      inflicted by modern weapons. New fields of medicine opened up, and nursing
      expanded as women rushed to help, never expecting the nearly unbearable
      conditions that they found on the battlefields of the Great War.

PMID- 15566216
TI  - Judicial recognition of nursing as a unique profession.

PMID- 15566217
TI  - Internet use in the OR--is it safe?

PMID- 15566218
TI  - Advocacy Day--in Washington and "on message".

PMID- 15566219
TI  - [Reaction of the physiological IOP in rabbits after application of the
      latanoprost (Xalatan) and amino acid L-arginine HCl mixture].
AB  - Authors present results of series of experiments focused to influence the IOP by
      antiglaucomatics in rabbits (New Zealand White) with physiological IOP. Adding of
      the 10% amino acid L-arginine x HCl to the 0.005% Xalatan eye drops intensifies
      activity of antiglaucomatics resulting in 9.5% average reduction of the IOP in a
      four-hour experiments (with maximum in 15th min.--19.3%), compared with
      application of both substances alone. Size of the pupil was not affected. Based
      on our experimental results we assume that the increased activity of the 0.005%
      Xalatan mixture with 10% amino acid L-arginine x HCl created a new complete
      metabolite--"bio-antiglaucomaticum". According to our observations this
      metabolite caused increase of the uveo-scleral outflow leading to the striking
      reduction of the physiological IOP in rabbits.

PMID- 15566220
TI  - [European Cataract Outcome Study--results of five years of participation].
AB  - GOAL: To inform about European Cataract Outcome Study and to publish results from
      the Department of Ophthalmology, Faculty Hospital in Hradec Kralove achieved
      during the five years' participation. METHOD, GROUPS: European Cataract Outcome
      Study is an international multicentric study pursuing quality of cataract surgery
      in individual departments of European countries. Its goal is to monitor the
      development of new trends and to be helpful in setting standards using the
      collected data. The Study evaluates results of all surgeries performed during one
      month. Our department participated in it in the years 1998-2002. In the first
      part of the trial the basic demographic data as well as the course of the
      surgeries were followed, in the second part results of examination during the
      first six months after the surgery were collected. RESULTS: Operations are mostly
      performed by means of the facoemulsification method in local anesthesia
      (subconjunctival or parabulbar), the stay in hospital varies in individual years
      between 35.1% and 56%, the percentage of implanted foldable (soft) intraocular
      lenses rises every year, in 2002 up to 61.5% (average of the whole study was
      78.2% in 2002), the percentage of posterior lens capsule rupture during the
      procedure during the five year period in our department descends (range 3.7% to
      1.2%). In the referred groups, 40.4% to 50.5% of eyes suffered from still another
      disease. The best corrected visual acuity 0.6 or better after the surgery
      achieved in individual years 64% to 78%. The deviation from planed refraction is
      between 0.69 to 0.88 diopters. The induced postoperative astigmatism varied in
      followed periods from 0.49 to 0.69 cylindrical diopters. CONCLUSION: The results
      of the study shows that the quality of surgeries performed in the department is
      on the high level and is fully comparable with contemporary European standard.

PMID- 15566221
TI  - [Evidence based medicine and cost-effectiveness analysis in ophthalmology].
AB  - GOAL: To make the reader familiar with the term evidence based medicine (EBM), to
      explain the principle of cost-effectiveness analysis (price-profit), and to show
      its usefulness to compare the effectiveness of different medical procedures.
      METHOD: Based on few examples, in this article the relevance and calculation of
      important parameters of cost-effectiveness analysis (CE), as utility value (UV),
      quality adjusted life years (QALY) is explained. In addition, calculation of UV
      and QALY for the cataract surgery, including its complications, is provided.
      RESULTS: According to this method, laser photocoagulation and cryocoagulation of
      the early stages of retinopathy of prematurity, treatment of amblyopia, cataract
      surgery of one or both eyes, from the vitreoretinal procedures the early
      vitrectomy in cases of hemophtalmus in proliferative diabetic retinopathy or grid
      laser photocoagulation in diabetic macular edema or worsening of the visual
      acuity due to the branch retinal vein occlusion belong to highly effective
      procedures. On the other hand, to the procedures with low cost effectiveness
      belongs the treating of the central retinal artery occlusion with anterior
      chamber paracentesis, as well as with CO2 inhalation, or photodynamic therapy in
      choroidal neovascularization in age-related macular degeneration with visual
      acuity of the better eye 20/200. CONCLUSION: Cost-effectiveness analysis is a new
      perspective method evaluating successfulness of medical procedure comparing the
      final effect with the financial costs. In evaluation of effectiveness of
      individual procedures, three main aspects are considered: subjective feeling of
      influence of the disease on the patient's life, objective results of clinical
      examination and financial costs of the procedure. According to this method, the
      cataract surgery, as well as procedures in the pediatric ophthalmology belong to
      the most effective surgical methods.

PMID- 15566222
TI  - [The therapy for acute acquired syphilitic uveitis].
AB  - PURPOSE: In retrospective study (analysis) to report the effectiveness of therapy
      on anatomic and functional outcomes in patients with acute acquired syphilitic
      uveitis. DESIGN: Retrospective case-control study. PARTICIPANTS: 3 patients (4
      eyes) with symptoms of ocular acute inflammation which occurred in latent stage
      of syphilis are included in our study. In all patients uveitis was the first
      clinical symptom of syphilis. METHODS: In all 3 patients the infection of
      acquired syphilis was diagnosed using specific and non-specific tests for
      treponemal antibody. In 2 eyes we performed diagnostic and therapeutic pars plana
      vitrectomy. The management of ocular syphilis in all patients consisted of mega
      units of aqueous penicillin intravenously or intramusculary, in 2 patients we
      used the combination with steroids. RESULTS: In 2 eyes with perioperatively
      obtained material of vitreous (during pars plana vitrectomy) specific treponemal
      antibody was detected using specific (TPHA) test. In the third patient infection
      was verified serologically. The final visual acuity of all 4 eyes is better than
      or equal to 6/12. The visual acuity of one exe is 6/6. CONCLUSION: Uveitis and
      neuroretinitis may be the first symptom of acquired syphilis in latent stage.
      Early antibiotic treatment significantly improves anatomical reparation of
      infection and visual outcomes.

PMID- 15566223
TI  - [Adenoma of the pituitary gland in the ophthalmologist's out-patient practice].
AB  - Authors describe eye and general symptoms in five patients with the adenoma of
      the pituitary gland, detected on the results of the ophthalmological examination.
      Identical symptoms in all patients were the decrease of central visual acuity or
      visual field defects. The general somatic manifestations of the disease were
      different.

PMID- 15566224
TI  - [Hemi-hangback recession (retroposition) of extraocular muscles].
AB  - In a small clinical study the author evaluates the efficiency of the hemi
      hangback recession (retroposition) procedure. This surgical procedure, which
      weakens extraocular muscles, proceeds from the hangback recession (retroposition)
      technique (hanging the muscle on a resorbable suture), which combines with the
      traditional recession. Hemi-hangback recession procedure is suitable in cases
      when a recession of more than 7 mm is needed. It is experimentally and clinically
      as well demonstrated in extra large recessions, that a shift towards the original
      insertion of the muscle occurs. The combination of the classical and hangback
      recession has its advantages in specific indications. More convenient surgical
      access and a reduction of the objectionable shift of the muscle backwards are
      main advantages of this procedure. The surgical procedure is described in this
      article and results in the group of patients from the Children's and Adult's
      Department of Ophthalmology at the Faculty Hospital in Motol, Prague, Czech
      republic. The hemi-hang-back muscles recession is indicated in third and sixth
      nerve palsies, restrictive forms of strabismus and complicated or successive
      forms of strabismus.

PMID- 15566225
TI  - [Ketotifen fumarate (Zaditen) eye drops in the treatment of seasonal allergic
      conjunctivitis].
AB  - A group of 25 patients with signs of seasonal allergic conjunctivitis treated
      during the period of 2 to 6 month with ketotifen fumarate 0.05% eye drops 2-3
      times daily (Zaditen eye drops, Novartis Ophthalmic, AG, Switzerland) is
      described here. As subjective symptoms of itching, stinging, tearing, and mucous
      discharge were observed and evaluated, as well as objective signs of hyperemia of
      the conjunctiva and hypertrophy of the tarsal papillae. Similarly the onset of
      action, duration time, and toleration of the drug were assessed. Subjective
      symptoms disappeared after 10 days of treatment duration in 60% to 80% patients,
      after two months of treatment were present in the range 0% to 20%. Objective
      signs diminished after 10 days of treatment in 60%-72% patients, and after 2
      months in 72% to 96% of patients. Hypertrophy of papillae of the tarsal
      conjunctiva did not totally disappear even after 6 month of treatment with
      ketotifen fumarate eye drops. Onset of action in all patients was 20 minutes or
      less, the duration of action was in the range of 8-13 hours. The drug was found
      as a good tolerable by all patients. Sixteen per cent of patients felt some
      burning following the instillation. The study states that ketotifen fumarate
      0.05% eye drops are effective in a monotherapy of seasonal allergic
      conjunctivitis. Due to its multiple action, the drug prevents the allergic
      reaction as well. Subjective symptoms are influenced faster and more effective
      than the objective signs. The treatment of objective signs needs prolonged use of
      these drops.

PMID- 15566226
TI  - [Nodular faciitis--rare localization on the eye (a case report)].
AB  - GOAL: To contribute to differential diagnosis of changes of the outer segment of
      the eye. CASE REPORT: A 43-years old woman with three weeks long history of fast
      growing painless focus in the nasal part of the sclera of the left eye, which
      caused, except of visible tubercle and moderate feeling pressure, no problems. It
      is an unusual localization of non-malignant disease of unknown etiology
      originating from the Tenon's capsule. The literature quotes the same histological
      finding in different organs; the localization in the eye is rare. The author
      considers difficulties of the differential diagnosis in the unusual ocular
      diagnosis. CONCLUSION: The diagnosis was specified on the basis of the ocular and
      following histological findings. The treatment is surgical.

PMID- 15566227
TI  - [Diseases of the vitreoretinal region. Part II].

PMID- 15566228
TI  - [Three physicians who treated trachoma in Slovakia].

PMID- 15566229
TI  - [Really only Vioxx?].

PMID- 15566230
TI  - [Aripiprazol. An atypical neuroleptic with exceptional mechanisms of action] ].

PMID- 15566231
TI  - [Altitude sickness].

PMID- 15566232
TI  - [International nonproprietary names. How it begins and what it asserts].

PMID- 15566234
TI  - [What is a cost benefit analysis?].

PMID- 15566233
TI  - [Antioxidants and atherosclerosis. What is certain in primary and secondary
      prevention?].

PMID- 15566235
TI  - [Licking bottle nipples?].

PMID- 15566236
TI  - [The best strategies against reflux disease. Acid stomach and the sequelae].

PMID- 15566237
TI  - [Incidence of hepatocellular carcinoma increases. The obese are especially
      endangered].

PMID- 15566238
TI  - [More women at the colonoscope, better sedation. Thus the acceptance of
      colonoscopy is increased].

PMID- 15566239
TI  - [To wash and clean until the hands bleed. By compulsions troubled -- by the
      physician neglected?].

PMID- 15566240
TI  - [New disease entities and new therapy concepts. The art of headache therapy].

PMID- 15566241
TI  - [After stroke threatens pneumonia. Antibiotics to be given prophylactically?].

PMID- 15566242
TI  - [Screening procedures in the family practice. What is the new fast allergy
      test?].

PMID- 15566243
TI  - [Somatoform disorders. Rather paying thousands Euro than accepting psychogenic
      causes].

PMID- 15566244
TI  - [Where physician-patient communications have failed. Physicians are not "health
      makers"].

PMID- 15566245
TI  - [Couples desiring children need comprehensive counseling. What to do about
      azoospermia?].

PMID- 15566246
TI  - [Andrological diagnosis and treatment of azoospermia].
AB  - 10-20% of the men who seek the help of an andrologist present with azoospermia.
      Possible causes are of genetic origin or are acquired disorders of production and
      transport. On the basis of a comprehensive andrological work-up this disturbances
      can be identified. In this connection important parameters for the clarification
      of azoospermia include patient history, endocrinal laboratory examinations,
      analysis of the ejaculate and genetic investigations. In addition to medication,
      microsurgical interventions may be useful. For assisted reproduction, sperm is
      harvested operatively from the testes or microsurgically from the epididymis.

PMID- 15566247
TI  - [ICSI with testicular and epididymal spermatozoa].
AB  - The use of epididymal or testicular sperm for ICSI should be employed only as a
      last resort to restore male reproductive function. Depending on whether the
      underlying cause of the infertility is obstructive or non-obstructive, prior
      appropriate genetic examinations are to be recommended. For the collection of
      sperm, microsurgical epididymal sperm aspiration (MESA) and TESE (testicular
      sperm extraction) are accepted methods. Today, cryopreservation of the sperm thus
      obtained is standard. In the event of obstructive causes, the pregnancy rate per
      treatment cycle is almost as high as with ICSI employing ejaculated spermatozoa.
      If existing genetic defects are excluded, congenital anomalies among the
      resulting children is presumably somewhat elevated in comparison with the normal
      population, although there are also studies that have failed to confirm this.

PMID- 15566248
TI  - [Donor (heterologous) insemination in Germany--medical and legal aspects].
AB  - Donor insemination is a scientifically based reliable treatment for infertile
      couples--in Germany too. Reported results and long-term experience are uniformly
      good: neither the parents nor the children suffer any impairment of quality of
      life; stabilization of the family situation, low divorce rates and the frequently
      expressed desire for repeat treatments all militate in favour of this therapeutic
      option. Legal uncertainties, such as reservations on the part of the physician,
      documentation, anonymity and protection for donors, physicians and parents are
      points are points to be addressed by legislators and the relevant professional
      organizations.

PMID- 15566249
TI  - [The non-healing wound].
AB  - The most common chronic wounds are pressure ulcers, diabetic ulcers, arterial
      occlusive disease and venous ulcers. The therapeutic aim after appropriate
      diagnostic work-up is causal treatment. Pressure relief, revascularisation or
      compression head the list of potential measures. Apart from local factors such as
      infection or necrosis, systemic factors such as patient compliance, renal
      insufficiency and immunosuppression are of relevance. If there is a chance of
      healing, wound management comprises repeated debridement and wet dressings. In
      the presence of an infection, local antiseptic treatment is indicated. In the
      individual case, wound stimulation can be supported by protease inhibitors,
      growth factors or tissue engineering. Definitive wound closure is achieved by
      epithelial migration from the margins of the wound, or by plastic surgery.
      Regular documentation of the course and success of wound healing is mandatory. In
      the wound care center, surgical disciplines, diabetology, dermatology and
      diagnostic work-up are coordinated, and liaison with the family doctor and home
      care providers practiced. This wound healing concept successfully heals
      approximately 80% of the cases of chronic wounds in 18.8 months (mean healing
      duration 4.8 months).

PMID- 15566250
TI  - [Pathological jealousy].
AB  - Pathological jealousy can make life unbearable for all concerned. The proximity
      of this condition to obsessive-compulsive phenomena has given rise to the notion
      that it might respond to substances of proven value in the treatment of obsessive
      compulsive disorders. This case history exemplifies the successful treatment of
      pathological jealousy with the selective serotonin reuptake inhibitor (SSRI)
      fluoxetine. The substance not only proved to be a successful antidepressant, but
      also effectively mitigated the anguish of the patient's pathological jealousy. On
      the basis of these findings, fluoxetine--as also other SSRIs--should always be
      considered as a possible effective pharmacological strategy for the treatment of
      pathological jealousy.

PMID- 15566253
TI  - [Risk patients are often insufficiently treated. LDL cholesterol to be held down
      even more vigorously].

PMID- 15566254
TI  - [Target values are more often attainable. Almost doubly so many patients with
      values under 100mg/dl].

PMID- 15566255
TI  - [Flatfoot on the long road to diagnosis].

PMID- 15566256
TI  - [Evaluating decubitus risk factors, a primary step in prevention].

PMID- 15566257
TI  - [The Geriatric Incidence and Prevention of Pressure Sores study, a study to
      reduce the risk].

PMID- 15566258
TI  - [Prevention of decubitus ulcers. Adaptable tools].

PMID- 15566259
TI  - [Prevention, a teamwork job].

PMID- 15566260
TI  - [Acute confusional syndrome as first manifestation of primary
      hyperparathyroidism].
AB  - Hyperparathyroid crisis is an uncommon clinical state characterized by severe
      hypercalcemia which can produce an acute confusional syndrome (ACS) or delirium.
      We are reporting the case of a 58-year male with calcemias greater than 14 mg/dl,
      that were due to a parathyroid adenoma (primary hyperparathyroidism), and caused
      his admission in UCI with change in the conscience level, global afectation of
      the cognitive functions, letargia and disorentiation among other clinical
      symptoms. The patient was operated by our Service on lower left parathyroidectomy
      with PTH rapid or turbo assay and decreasing such hormone levels about 75%. After
      the surgery his evolution was satisfactory obtaining the normocalcemia.

PMID- 15566261
TI  - [Benign tumors of the parotid gland].
AB  - We review patients operated of parotidectomy in our ENT department of Dr. Peset
      Hospital from Valencia during the period 1975-2001. We shelted an amount of 145
      cases. The pathologic distribution between benign and malign tumors was as
      following: 119 benign tumors (83%) and 26 malign tumors (17%). Here we study
      benign parotid tumors, which represent 83% of total parotid tumors. We performed
      suprafacial parotidectomies in 72% and total parotidectomy in 19% of cases.
      Nodulectomy was realized in 9% of patients in those tumors that arise in the
      lower part of the parotid gland and usualy they were Warthin tumors. The main
      complications of surgery were facial nerve dysfunction and Frey syndrome. We
      didn't have any case of permanent facial nerve dysfunction but transitory facial
      nerve disfunction occurred in 26% of patients. Frey syndrome appeared in 10% of
      patients operated of parotidectomy. Benign mixed tumor was the only one benign
      tumor in recurring and the frequency was 5% of patients.

PMID- 15566262
TI  - [Diagnostic implication of the ENT in the Wegener granulomatose].
AB  - Wegener granulomatose is an granulomatous necrotisant vasculitis of unknown
      ethiology that can affect in a classical form the superior and inferior
      respiratory tract and kidney. The possibility that the illness is limited to the
      ENT sphere together to a good accessibility for the biopsy of the nasal fossae
      and sinus usually convert the ENT in the first specialist for the diagnosis of
      the illness. It is a systemic illness with a frequent and important ENT
      expression. We have he possibility to establish an earlier diagnosis with
      prognostic implications in those patients with ENT clinic. So these patients can
      benefit the treatment with Cotrimoxazol. We have done a revision of the patients
      affected of Wegener granulomatose with ENT clinic, treated in the last ten years
      in our Hospital. We present 9 cases, exposing the age of diagnosis, the initial
      data, the topographic extension along the illness, the diagnostic methods and the
      treatment and evolution.

PMID- 15566263
TI  - [Larynx lymphoepithelioma].
AB  - We present a case of lymphoepithelioma of the larynx, a very rare tumour in this
      location. The relationship between lymphoepithelial carcinoma of the larynx and
      Epstein-Barr virus, is still controversial. We describe one new case of this
      tumour involving the supraglottis, and it's surgery and radioterapic treatment.
      The diagnostic problems and therapy associated with this rare tumour are
      discussed.

PMID- 15566264
TI  - [Chronic otitis media in adults complicated with meningitis. Report of two
      cases].
AB  - Although rare, meningitis secondary to chronic media otitis represent an
      intracranial complication of importance nowdays. We are reporting two clinical
      cases diagnosed by symptoms, CT and lumbar punction as meningeal syndrome with
      otogenic cause that required endovenous wide spectrum antibiotic treatment and
      surgery later. We consider essential an early diagnosis and close cooperation
      with other departments to try to decrease the associated mortality, greater than
      30% in some series.

PMID- 15566265
TI  - [Bilateral peripheral facial paralysis secondary to Lyme disease].
AB  - Simultaneous bilateral facial paralisis (SBFP) occurs in 0.3-2% of all facial
      paralisis. We report a case of SBFP in association with Lyme disease. A review of
      literature about SBFP is made, studing specially the one caused by Borrelia
      burgdorferi. We present a diagnostic guideline of SBFP. Suspect diagnosis of Lyme
      disease is based on clinical and epidemiological criteria. Culture isolation of
      this bacteria is difficult, therefore serologic testing is required.
      Neuroborreliosis treatment is intravenous Ceftriaxone or Cefotaxime. Oral
      Doxycycline is useful in the treatment of neuritis without central nervous system
      involvement.

PMID- 15566266
TI  - [Treatment and complications of oesophagic foreign bodies].
AB  - OBJECTIVE: Revision of characteristics and diagnosis methods and treatment of
      foreign bodies (FB) embed in the oesophagus (OFB). METHOD: We have realized a
      retrospective study since 1994 to 2002, with 77 cases with suspicion of ingestion
      of the (OFB) treated in our ENT Service. RESULTS: We realized a total of 83
      oesophagoscopies, flexible and rigid, that reaveled the oesophagic superior
      third, as the most common place of embedding, dysphagia as the most predominant
      symptom and coins and bones as the most common type of FB. Most of the cases did
      not present any kind of complications, but we present a case of death.
      CONCLUSIONS: The oesophagoscopies are a very useful method conditioned by the
      kind of FB and experience of the surgeon. We must not subestimate the
      complications of the embedding of the OFB, because they can be mortals, although
      they are.

PMID- 15566267
TI  - [Eagle's syndrome. Report of a case and literature review].
AB  - Eagle's syndrome produces recurrent throat pain, foreign body sensation,
      dysphagia/odinophagia or facial pain due to an elongated styloid process or
      calcified stylohyoid ligament. We report the clinical case of a 56 years old
      female who had consulted several times to our by Emergency Service relating these
      symptoms and she was finally diagnosed as this uncommon pathology. Up to now the
      patient has been controled with analgesics but not surgical treatment. We have
      performed a short bibliographic review about this syndrome.

PMID- 15566268
TI  - [Ethmoidal epidermoid carcinoma showing as cluster headache. Report of a case and
      literature review].
AB  - We report the case of a 54 years old male diagnosed as ethmoidal epidermoid
      carcinoma which, after almost 1 year--asymptomatic period, debuted with facial
      pain (cluster headache) without another associated clinic. Sino-nasal malignant
      tumours represent about 5%-6% in all ENT carcinomas and they use to be of later
      diagnosis, with high probability of local recurrence and invasiveness on
      structures like orbit and skull base. The main treatment for ethmoidal squamous
      carcinomas is surgery and depending on staging can require radiotherapy and/or
      chemotherapy. A bibliographic review is done at this respect.

PMID- 15566269
TI  - [Anatomic study of parapharyneal space].
AB  - The parapharyngeal space is considered the key space of the suprahioid neck,
      being essential to establish the origin and anatomic relations of the lesions of
      the profound neck. The descriptions of the fascial limits of the parapharyngeal
      space are variable in the litterature, reflecting some ambiguity in the manuals
      of anatomy and surgery. We have done a detailed study of this region, working on
      5 cadavers, fixed in a solution of phenol and alcohol, and correlating the
      disection pieces with a radiologic study. The goal has been to improve our
      anatomic knowledge of the suprahioid neck, to be able to establish an anatomo
      clinic-radiologic correlation of the lesions of this region, to be able to
      establish an differential diagnosis, predict possible ways of dissemination and
      facilitate the most proper surgical approach.

PMID- 15566270
TI  - Piot issues call to action at AIDS summit in Bangkok.

PMID- 15566271
TI  - The development of the Greek health care system.

PMID- 15566272
TI  - Population health in Europe: how much is attributable to health care?
AB  - Does health care save lives? Commentators such as McKeown and Illich, writing in
      the 1960s, argued that it contributed very little to population health, and might
      even be harmful. However, they were writing about a period when health care had
      relatively little to offer compared to today. More recent reviews of the
      contribution of health care to health have led to a consensus that McKeown was
      correct to the extent that 'curative medical measures played little role in
      mortality decline prior to mid-20th century'. But the rapidly changing scope and
      nature of health care means it cannot be assumed that this is still the case.
      Thus, several writers have described often quite substantial improvements in
      death rates from conditions for which effective interventions have been
      introduced. Yet the debate continues, with some arguing that health care is
      making an increasingly important impact on overall levels of health while others
      contend that it is in the realm of broader policies, such as education, transport
      and housing that we should look to for future advances in health. Inevitably,
      this is to a considerable extent a false dichotomy. Both are important. But how
      much does health care contribute to population health?

PMID- 15566273
TI  - Health care governance in the UK National Health Service.
AB  - The NHS Plan sets out a challenging agenda for modernising the UK National Health
      Service (NHS), governing the organisation's performance and improving and
      extending service provision. Good health care governance is an essential
      prerequisite for all modernisation effort. This article will explore the
      responsibilities and implications for health care boards, managers and clinical
      staff in providing assurances for health care governance. Health care
      organisation directors, executive and non-executive, all share responsibility for
      the direction and control of the organisation. They are required to act in the
      best interest of the patients, staff and the general public and have statutory
      obligations to provide safe systems of work under the Health and Safety
      Regulations. Each director has a role in ensuring openness, being honest and
      acting with integrity, taking responsibility for their own personal learning and
      development, constructively challenge and develop strategy and ensuring the
      probity of the organisation's activities.

PMID- 15566274
TI  - The national programme for IT in the UK National Health Service.

PMID- 15566275
TI  - Planning and design for a culture of safety in Thessaloniki's hospitals.
AB  - Thessaloniki is the second capital of Greece, located in the region of Macedonia,
      in the northern part of the Greek mainland. After the opening of the boarders of
      the former 'Eastern Block' countries and following their general open-policy to
      the European Union, Thessaloniki became an important part of the Balkans
      Initiative, aiming at attracting patients from abroad to Greece. Thus, some of
      the most modern hospitals in Greece are near Thessaloniki. Patient safety forms
      an important issue of the policy attracting patients. With this paper an attempt
      will be made to examine the characteristics of a culture of safety embodied in
      the planning and design of two of Thessaloniki's hospitals. These characteristics
      are to be found in the health care environment of the present clinical processes,
      on both, a quantitative and a qualitatve basis, and finally, suggestions for
      further development.

PMID- 15566276
TI  - Implementing telemedicine technology: lessons from India.
AB  - Information and communications technologies have universally helped to bridge the
      digital divide. As an application of ICT, telemedicine is an efficient pathway
      for enabling health care delivery. Developing countries, too, have started
      reaping the benefits of this evolutionary technology, but realisation of such
      dreams has not been swift. The implementation of a pilot scheme in telemedicine
      in India has been confounded with challenges right from the very start. One of
      the prime lessons to be learnt from the implementation of a pilot project in a
      developing country is to keep the objectives of the project in small modules and
      to keep the deliverables within sight. An account of some of the challenges faced
      while developing telemedicine technology in India serves as a useful example for
      upcoming telemedicine programmes in Third World countries.

PMID- 15566277
TI  - Are Spanish physicians ready to take advantage of the Internet?
AB  - OBJECTIVE: To analyze specialist doctors' opinions, attitudes and habits with
      respect to e-health, and the repercussions of these factors on doctor/patient
      relations. METHODOLOGY: Use of a survey to analyse attitudes, Internet use,
      habits and opinions about the advantages and disadvantages of the Internet among
      302 doctors in eight Spanish hospitals. RESULTS: Of the doctors surveyed, 80%
      have access to and use the Internet. Almost 40% use the Internet for less than
      one hour a day; doctors in smaller hospitals spend more time on the Internet and
      men spend more time than women. The most frequently visited websites are PubMed
      (11%) and Google (22%); when choosing a website, periodical updating and prestige
      are important to 78% and 69%, respectively; 37% have taken a course through the
      Internet; 35% consult electronic journals systematically; 16% regularly
      collaborate with, or write materials for healthcare websites; 12% receive
      electronic mail from their patients. Three clusters of information were generated
      in this study to classify the participating hospital doctors: the different types
      of information the doctors consulted, the way the Internet enhances
      doctor/patient relations and the aspects that the doctors consider relevant when
      connecting to the Internet. CONCLUSIONS: Spanish doctors consider the Internet to
      be a tool that enhances doctor/patient relations. New technologies are
      accelerating the substitution of a paternalistic model by ones where the patient
      has access to more information and resources. There appears to be a favourable
      attitude towards seeking a second opinion through the Internet, although not
      towards patients' 'chats'.

PMID- 15566278
TI  - The global challenge of diabetes.
AB  - Diabetes is one of the main causes of death in most developed countries. Both
      types of diabetes are spreading across the globe at an alarming rate, driving the
      condition to become one of the most challenging health problems of the 21st
      Century. Prevention is essential, and promoting a healthy lifestyle, early
      screening and investment in national programmes are key to putting the scourge of
      diabetes on hold. The International Diabetes Federation (IDF) plays a crucial
      role in the global fight against diabetes. Its objectives are to improve
      diagnosis, care and treatment of diabetes; promote educational and training
      programmes; develop insulin availability and affordability and raise awareness of
      the condition. The IDF hopes that these actions will not only save but also
      enhance the lives of people with diabetes.

PMID- 15566279
TI  - Musings on the future of health care systems.

PMID- 15566280
TI  - Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of
      severe acute respiratory syndrome 3CLpro.
AB  - The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS)
      coronavirus is a key target for structure-based drug design against this viral
      infection. The enzyme recognizes peptide substrates with a glutamine residue at
      the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at
      the alpha-position were synthesized and tested as reversible inhibitiors against
      SARS 3CL(pro). Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based
      "warheads" generated significantly better inhibitors (4a-c, 8a-d) with IC(50)
      values ranging from 0.60 to 70 microM.

PMID- 15566281
TI  - Identification of a small molecule nonpeptide active site beta-secretase
      inhibitor that displays a nontraditional binding mode for aspartyl proteases.
AB  - A small molecule nonpeptide inhibitor of beta-secretase has been developed, and
      its binding has been defined through crystallographic determination of the enzyme
      inhibitor complex. The molecule is shown to bind to the catalytic aspartate
      residues in an unprecedented manner in the field of aspartyl protease inhibition.
      Additionally, the complex reveals a heretofore unknown S(3) subpocket that is
      created by the inhibitor. This structure has served an important role in the
      design of newer beta-secretase inhibitors.

PMID- 15566282
TI  - Arylthioindoles, potent inhibitors of tubulin polymerization.
AB  - Several arylthioindoles had excellent activity as inhibitors both of tubulin
      polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3
      [(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), the most
      potent derivative, showed IC(50) = 2.0 microM, 1.6 times more active than
      colchicine and about as active as combretastatin A-4 (CSA4). Compound 21
      inhibited the growth of the MCF-7 cells at IC(50) = 13 nM. Colchicine and CSA4
      had 13 nM and 17 nM IC(50) values, respectively, with these cells.

PMID- 15566283
TI  - Lactams as EP4 prostanoid receptor agonists. 3. Discovery of N-ethylbenzoic acid
      2-pyrrolidinones as subtype selective agents.
AB  - Two distinct synthetic schemes were applied to access heteroatom-containing alpha
      chain lactams or lactams terminated as aryl acids. The latter lactams were
      devised using a pharmacophore for EP(4) receptor activity. gamma-Lactams were
      characterized for their prostanoid EP receptor affinities and EP(4) activity and
      found to be selective for the EP(2) and EP(4) receptors or selective for the
      EP(4) subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.

PMID- 15566284
TI  - Novel azido and isothiocyanato analogues of [3-(4-phenylalkylpiperazin-1
      yl)propyl]bis(4-fluorophenyl)amines as potential irreversible ligands for the
      dopamine transporter.
AB  - Potential irreversible ligands were prepared, based on a series of 3-(1
      piperazinyl)propyl-N,N-bis(4-fluorophenyl)amines, as molecular probes for the
      dopamine transporter (DAT). Both azido- and isothiocyanato-substituted
      phenylalkyl analogues were synthesized and evaluated for displacement of
      [(3)H]WIN 35 428 in rat caudate putamen tissue. All of the analogues showed
      moderate binding potencies at the DAT. The azido analogue, 16b, was
      radioiodinated and used to photolabel human DAT-transfected HEK 293 cell
      membranes. [(125)I]16b irreversibly labeled an approximately 80 kDa band
      corresponding to the DAT detected by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. This radioligand provides a novel addition to the growing
      arsenal of structurally diverse irreversible ligands that are being used to
      identify binding domains on the DAT. Characterizing points of attachment of these
      irreversible probes to the DAT protein will ultimately help elucidate the three
      dimensional arrangement of the transmembrane domains, identify individual binding
      sites of the DAT inhibitors, and direct future drug design.

PMID- 15566285
TI  - CoMFA study of piperidine analogues of cocaine at the dopamine transporter:
      exploring the binding mode of the 3 alpha-substituent of the piperidine ring
      using pharmacophore-based flexible alignment.
AB  - A 3D-QSAR CoMFA study of piperidine-based analogues of cocaine with flexible 3
      alpha-substituents is described. A series of pharmacophore models were generated
      based on three representative compounds 1p, 2i, and 3c using the Genetic
      Algorithm Similarity Program (GASP) method. The flexible superposition of all
      studied compounds was performed for each pharmacophore model using the FlexS
      algorithm and the three-dimensional structure of 2i as a template. All sets of
      the overlaid structures with the top-ranked conformers were used for CoMFA
      modeling. Two best initial CoMFA models were selected and further optimized by
      identifying the best-fitting conformer of each compound. Compared with the
      initial models, the conventional correlation coefficients r(2) for the optimized
      models 1 and 2 were improved from 0.90 and 0.837 to 0.997 and 0.993,
      respectively. The leave-one-out cross-validated coefficients q(2) for the
      optimized models 1 and 2 were improved from 0.515 and 0.296 to 0.828 and 0.849,
      respectively. The results of the two CoMFA models suggest that both steric and
      electrostatic interactions play important roles in the binding of the 3 alpha
      substituents of the piperidine-based analogues of cocaine. The contributions from
      steric and electrostatic fields for model 1 were 0.621 and 0.379, respectively.
      The contributions from steric and electrostatic fields for model 2 were 0.493 and
      0.507, respectively. The two highly predictive CoMFA models indicate that the 3
      alpha-substituent has two possible binding modes at the DAT. The CoMFA contour
      maps provide a visual representation of prospective binding modes of the 3 alpha
      substituent of the piperidine-based analogues of cocaine and can be used to
      design novel DAT inhibitors that may be useful for the treatment of cocaine abuse
      and certain neurological disorders.

PMID- 15566286
TI  - A 3D similarity method for scaffold hopping from known drugs or natural ligands
      to new chemotypes.
AB  - A primary goal of 3D similarity searching is to find compounds with similar
      bioactivity to a reference ligand but with different chemotypes, i.e., "scaffold
      hopping". However, an adequate description of chemical structures in 3D
      conformational space is difficult due to the high-dimensionality of the problem.
      We present an automated method that simplifies flexible 3D chemical descriptions
      in which clustering techniques traditionally used in data mining are exploited to
      create "fuzzy" molecular representations called FEPOPS (feature point
      pharmacophores). The representations can be used for flexible 3D similarity
      searching given one or more active compounds without a priori knowledge of
      bioactive conformations or pharmacophores. We demonstrate that similarity
      searching with FEPOPS significantly enriches for actives taken from in-house high
      throughput screening datasets and from MDDR activity classes COX-2, 5-HT3A, and
      HIV-RT, while also scaffold or ring-system hopping to new chemical frameworks.
      Further, inhibitors of target proteins (dopamine 2 and retinoic acid receptor)
      are recalled by FEPOPS by scaffold hopping from their associated endogenous
      ligands (dopamine and retinoic acid). Importantly, the method excels in
      comparison to commonly used 2D similarity methods (DAYLIGHT, MACCS, Pipeline
      Pilot fingerprints) and a commercial 3D method (Pharmacophore Distance Triplets)
      at finding novel scaffold classes given a single query molecule.

PMID- 15566287
TI  - alpha 2-adrenoreceptors profile modulation. 2. Biphenyline analogues as tools for
      selective activation of the alpha 2C-subtype.
AB  - A series of derivatives structurally related to biphenyline (3) was designed with
      the aim to modulate selectivity toward the alpha(2)-AR subtypes. The results
      obtained demonstrated that the presence of a correctly oriented function with
      positive electronic effect (+sigma) in portion X of the ligands is an important
      factor for significant alpha(2C)-subtype selectivity (imidazolines 5, 13, 16, and
      19). Homology modeling and docking studies support experimental data and
      highlight the crucial role for the hydrogen bond between the pyridine nitrogen in
      position 3 of 5 and the NH-indole ring of Trp6.48, which is favorably oriented in
      the alpha(2C)-subtype, only.

PMID- 15566288
TI  - Raptor: combining dual-shell representation, induced-fit simulation, and
      hydrophobicity scoring in receptor modeling: application toward the simulation of
      structurally diverse ligand sets.
AB  - We present a novel receptor-modeling approach (software Raptor) based on
      multidimensional quantitative structure-activity relationships (QSARs). To
      accurately predict relative free energies of ligand binding, it is of utmost
      importance to simulate induced fit. In Raptor, we explicitly and anisotropically
      allow for this phenomenon by a dual-shell representation of the receptor
      surrogate. In our concept, induced fit is not limited to steric aspects but
      includes the variation of the physicochemical fields along with it. The
      underlying scoring function for evaluating ligand-receptor interactions includes
      directional terms for hydrogen bonding and hydrophobicity and thereby treats
      solvation effects implicitly. This makes the approach independent from a partial
      charge model and, as a consequence, allows one to smoothly model ligand molecules
      binding to the receptor with different net charges. We have applied the new
      concept toward the estimation of ligand-binding energies associated with the
      chemokine receptor-3 (50 ligands: r(2) = 0.965; p(2) = 0.932), the bradykinin
      B(2) receptor (52 ligands: r(2) = 0.949; p(2) = 0.859), and the estrogen receptor
      (116 ligands: r(2) = 0.908; p(2) = 0.907), respectively.

PMID- 15566289
TI  - Discovery of bicyclic thymidine analogues as selective and high-affinity
      inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.
AB  - Thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt) represents
      an attractive target for selectively blocking bacterial DNA synthesis. Hereby, we
      report on the discovery of a novel class of bicyclic nucleosides (10 and 11) and
      one dinucleoside (12), belonging to the most selective inhibitors of TMPKmt
      discovered so far.

PMID- 15566290
TI  - New COX-2/5-LOX inhibitors: apoptosis-inducing agents potentially useful in
      prostate cancer chemotherapy.
AB  - The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and
      lipoxygenases (LOXs) have been found to be implicated in a variety of cancers,
      including prostate cancer. To develop new therapeutic treatments, it therefore
      seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the
      synthesis and in vitro pharmacological properties of diarylpyrazole derivatives
      that have in their structure key pharmacophoric elements to obtain optimal
      interaction with subsites of active pockets in both enzyme systems. Using a
      molecular modeling approach, a set of SAR data is proposed, highlighting the
      importance of the sulfonyl group of one of the aryl moieties in terms of
      proliferation inhibition and/or apoptosis induction.

PMID- 15566291
TI  - Synthesis, biological evaluation, and molecular modeling studies of a novel,
      peripherally selective inhibitor of catechol-O-methyltransferase.
AB  - A novel series of potent, peripherally selective, and long-acting inhibitors of
      catechol-O-methyltransferase (COMT) has been synthesized. The introduction and
      nature of heteroatom-containing substituents to the side-chain of the
      nitrocatechol pharmacophore was found to have a profound effect on both
      peripheral selectivity and duration of COMT inhibition in the mouse. This
      approach led to the discovery of 1-(3,4-dihydroxy-5-nitrophenyl)-3-[4-[3
      (trifluoromethyl)phenyl]-1-piperazinyl]-1-propanone hydrochloride 35 (BIA 3-335),
      which was found to possess a superior inhibitory profile in vivo over both the
      nonselective inhibitor tolcapone 1 and the peripherally selective but short
      acting entacapone 2. In this model, 35 retained 75% inhibition of peripheral COMT
      at 6 h after oral administration, yet significantly, only a minor reduction of
      central (cerebral) COMT activity was observed. Molecular modeling techniques were
      applied to review the analysis of the ternary enzyme-inhibitor complex previously
      determined by X-ray crystallography and to provide a deeper understanding of the
      structure-activity relationships within this novel series. Furthermore, a
      computational approach was applied in an effort to elucidate the particular
      structural factors relevant to the poor blood-brain permeability of 35. In
      conclusion, the improved biological properties herein reported reveal 35 as a
      candidate for clinical studies as an adjunct to L-DOPA therapy for Parkinson's
      disease.

PMID- 15566292
TI  - Novel bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines
      as highly potent and selective adenosine A2A receptor antagonists.
AB  - A series of bicyclic piperazine derivatives of triazolotriazine and
      triazolopyrimidines was synthesized. Some of these analogues show high affinity
      and excellent selectivity for adenosine A(2a) receptor versus the adenosine A(1)
      receptor. Structure-activity-relationship (SAR) studies based on
      octahydropyrrolo[1,2-a]pyrazine and octahydropyrido[1,2-a]pyrazine with various
      capping groups are reported. Among these analogues, the most potent and selective
      A(2a) antagonist 26 h has a K(i) value of 0.2 nM and is 16 500-fold selective
      with respect to the A(1) receptor. Among a number of compounds tested, compounds
      21a and 21c exhibited significantly improved metabolic stability. Compounds 21a,
      21c, and 18a showed good oral efficacy in rodent catalepsy models of Parkinson's
      disease.

PMID- 15566293
TI  - Broad-based quantitative structure-activity relationship modeling of potency and
      selectivity of farnesyltransferase inhibitors using a Bayesian regularized neural
      network.
AB  - Inhibitors of the enzyme farnesyltransferase show potential as novel anticancer
      agents. There are many known inhibitors, but efforts to build predictive SAR
      models have been hampered by the structural diversity and flexibility of
      inhibitors. We have undertaken for the first time a QSAR study of the potency and
      selectivity of a large, diverse data set of farnesyltransferase inhibitors. We
      used novel molecular descriptors based on binned atomic properties and invariants
      of molecular matrices and a robust, nonlinear QSAR mapping paradigm, the Bayesian
      regularized neural network. We have built robust QSAR models of
      farnesyltransferase inhibition, geranylgeranyltransferase inhibition, and in vivo
      data. We have derived a novel selectivity index that allows us to model potency
      and selectivity simultaneously and have built robust QSAR models using this index
      that have the potential to discover new potent and selective inhibitors.

PMID- 15566294
TI  - Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7
      tetrabromobenzimidazole.
AB  - Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein
      kinase whose abnormally high constitutive activity is suspected to underlie its
      pathogenic potential in neoplasia and infective diseases. Thus, CK2 inhibitors
      designed to dissect the signaling pathways affected by this kinase, in
      perspective, may give rise to pharmacological tools. One of the most successful
      CK2 inhibitors is TBB (4,5,6,7-tetrabromobenzotriazole). Here we show that its
      inhibitory properties can be markedly improved by generating adducts in which
      N(2) is replaced by a carbon atom bound to a variety of polar functions. The most
      efficient inhibitor is 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (2c)
      followed by the methylsulfanyl (8), isopropylamino (2e), and amino (2a)
      congeners. All these compounds display K(i) values <100 nM (40 nM in the case of
      2c). 2c induces apoptosis of Jurkat cells more readily than TBB (DC(50) value 2.7
      vs 17 microM) and, unlike TBB, it does not display any side effect on
      mitochondria polarization up to 10 microM concentration. Molecular modeling of
      the CK2-2c complex, based on the crystal structure of the CK2-TBB complex
      suggests that a number of additional apolar contacts between its two methyl
      groups and hydrophobic residues nearby could account for its superior inhibitory
      properties. Consequently, 2c is even more susceptible than TBB to mutations of
      the unique hydrophobic residues V66 and/or I174 to alanine. We propose to adopt
      2c as first choice CK2 inhibitor instead of TBB, especially for in cell studies.

PMID- 15566295
TI  - Acetylcholinesterase inhibitory activity of scopolin and scopoletin discovered by
      virtual screening of natural products.
AB  - For the targeting selection of acetylcholinesterase (AChE) inhibitors from
      natural sources we generated a structure-based pharmacophore model utilizing an
      in silico filtering experiment for the discovery of promising candidates out of a
      3D multiconformational database consisting of more than 110,000 natural products.
      In our study, scopoletin (1) and its glucoside scopolin (2) emerged as potential
      AChE inhibitors by the virtual screening procedure. They were isolated by
      different chromatographic methods from the medicinal plant Scopolia carniolica
      Jaqc. and tested in an enzyme assay using Ellman's reagent. They showed moderate,
      but significant, dose-dependent and long-lasting inhibitory activities. In the in
      vivo experiments (icv application of 2 micromol) 1 and 2 increased the
      extracellular acetylcholine (ACh) concentration in rat brain to about 170% and
      300% compared to basal release, respectively. At the same concentration, the
      positive control galanthamine increased the ACh concentration to about the same
      level as 1. These are the first in vivo results indicating an effect of coumarins
      on brain ACh.

PMID- 15566296
TI  - Synthesis and structure-activity relationships of 4-alkynyloxy phenyl sulfanyl,
      sulfinyl, and sulfonyl alkyl hydroxamates as tumor necrosis factor-alpha
      converting enzyme and matrix metalloproteinase inhibitors.
AB  - A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and
      piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure
      activity relationships, against tumor necrosis factor-alpha (TACE) and matrix
      metalloproteinase (MMP) inhibitor activities, are presented by investigating the
      oxidation state on sulfur and altering the P1' substituent. The sulfonyl
      derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors
      over the MMPs tested. The sulfinyl derivatives showed a preference for a specific
      oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also
      demonstrated in the sulfonyl series. The enhanced cellular activity was achieved
      upon incorporating a butynyloxy substituent in the piperidene series. Compounds
      64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg
      po.

PMID- 15566297
TI  - Effects of indole fatty alcohols on the differentiation of neural stem cell
      derived neurospheres.
AB  - In a search for inducers of neuronal differentiation to treat neurodegenerative
      diseases such as Alzheimer's disease, a series of indole fatty alcohols (IFAs)
      were prepared. 13c (n = 18) was able to promote the differentiation of neural
      stem cell derived neurospheres into neurons at a concentration of 10 nM. Analysis
      of the expression of the Notch pathway genes in neurospheres treated during the
      differentiation phase with 13c (n = 18) revealed a significant decrease in the
      transcription of the Notch 4 receptor.

PMID- 15566298
TI  - The discovery of orally active triaminotriazine aniline amides as inhibitors of
      p38 MAP kinase.
AB  - A new structural class of triaminotriazine aniline amides possessing potent p38
      enzyme activity has been discovered. The initial hit (compound 1a) was identified
      through screening the Pharmacopeia ECLiPS compound collection. SAR modification
      led to the identification of a short acting triaminotriazine aniline methoxyamide
      (compound 1m) possessing in vitro and in vivo oral activity in animal models of
      acute and chronic inflammatory disease. An X-ray crystal structure of compound 1m
      in this class, cocrystallized with unactivated p38 alpha protein, indicates that
      these compounds bind to the ATP binding pocket and possess key H-bonding
      interactions within a deeper cleft. Hydrogen bonding between one of the triazine
      nitrogens and the backbone NH of the Met109 residue occurs through a water
      molecule. The methoxyamide NH and carbonyl oxygen are within H-bonding distance
      of Glu71 and Asp168.

PMID- 15566299
TI  - An in silico approach to discovering novel inhibitors of human sirtuin type 2.
AB  - Type 2 human sirtuin (SIRT2) is a NAD(+)-dependent cytoplasmic protein that is
      colocalized with HDAC6 on microtubules. SIRT2 has been shown to deacetylate alpha
      tubulin and to control mitotic exit in the cell cycle. To date, some small
      molecular inhibitors of SIRT2 have been identified; however, more inhibitors are
      still needed to improve the understanding of SIRT2 biological function and to
      discover its possible therapeutic indications. In this paper, an in silico
      identification procedure is described for discovering novel SIRT2 inhibitors.
      Molecular modeling and virtual screening were utilized to find potential
      compounds, which were then subjected to experimental tests for their SIRT2
      inhibitory activity. Five of the 15 compounds tested in vitro showed inhibitory
      activity toward SIRT2, yielding a hit ratio of 33% in a micromolar level and thus
      demonstrating the usefulness of this procedure in finding new bioactive
      compounds. Two of the five compounds yielded in vitro IC(50) values of 56.7 and
      74.3 microM, and these can be considered as novel inhibitors of SIRT2. On the
      basis of our results, a phenol moiety on the active compound is suggested to be
      important for SIRT2 inhibitory activity. This phenol group, together with a
      hydrophobic moiety and hydrogen-bonding features, is suggested to form an active
      SIRT2 pharmacophore.

PMID- 15566300
TI  - Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a
      cell- and caspase-based high-throughput screening assay. 1. Structure-activity
      relationships of the 4-aryl group.
AB  - By applying a novel cell- and caspase-based HTS assay, 2-amino-3-cyano-7
      (dimethylamino)-4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been
      identified as a potent apoptosis inducer. Compound 1a was found to induce nuclear
      fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage
      and to induce apoptosis as determined by the flow cytometry analysis assay in
      multiple human cell lines (e.g. Jurkat, T47D). Through structure-activity
      relationship (SAR) studies of the 4-aryl group, a 4- and 7-fold increase in
      potency was obtained from the screening hit 1a to the lead compounds 2-amino-4-(3
      bromo-4,5-dimethoxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (1c) and 2-amino
      3-cyano-7-(dimethylamino)-4-(5-methyl-3-pyridyl)-4H-chromene (4e), with an EC(50)
      of 19 and 11 nM in the caspase activation assay in T47D breast cancer cells,
      respectively. The 2-amino-4-aryl-3-cyano-7-(dimethylamino)-4H-chromenes also were
      found to be highly active in the growth inhibition MTT assay, with GI(50) values
      in the low nanomolar range for compound 1c. Significantly, compound 1c was found
      to have a GI(50) value of 2 nM in the paclitaxel resistant, p-glycoprotein
      overexpressed, MES-SA/DX5 tumor cells. Functionally, compound 1c was found to be
      a potent inhibitor of tubulin polymerization and to effectively inhibit the
      binding of colchicine to tubulin. These results confirm that the cell-based
      caspase activation assay is a powerful tool for the discovery of potent apoptosis
      inducers and suggest that the 4-aryl-4H-chromenes have the potential to be
      developed into future anticancer agents.

PMID- 15566301
TI  - Tetrasubstituted imidazole inhibitors of cytokine release: probing substituents
      in the N-1 position.
AB  - We prepared novel 1,2,4,5-tetrasubstituted imidazole derivatives with high anti
      inflammatory activity by using our previously described regiospecific synthesis.
      Systematic optimization of the imidazole N-1 substituent resulted in compound 9b
      that potently inhibited the mitogen-activated protein kinase p38 (p38 IC(50) =
      0.218 microM) as well as the release of the proinflammatory cytokines interleukin
      1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) from human whole
      blood after stimulation with LPS. Furthermore, compound 9b exhibited reduced
      cytochrome P450 interaction in comparison with SB203580. This result is
      particularly important, since cytochrome P450 interaction is observed for some
      p38 inhibitors and in turn can potentially cause drug-drug interaction or lead to
      other hepatic changes such as P450 enzyme induction.

PMID- 15566302
TI  - Synthesis and structure-activity relationships of novel histamine H1 antagonists:
      indolylpiperidinyl benzoic acid derivatives.
AB  - A series of indolylpiperidinyl derivatives were prepared and evaluated for their
      activity as histamine H(1) antagonists. Structure-activity relationship studies
      were directed toward improving in vivo activity and pharmacokinetic profile of
      our first lead (1). Substitution of fluorine in position 6 on the indolyl ring
      led to higher in vivo activity in the inhibition of histamine-induced cutaneous
      vascular permeability assay but lower selectivity toward 5HT(2) receptor.
      Extensive optimization was carried out within this series and a number of
      histamine H(1) antagonists showing potency and long duration of action in vivo
      and low brain penetration or cardiotoxic potential were identified. Within this
      novel series, indolylpiperidines 15, 20, 48,51 and 52 exhibited a long half-life
      in rat and have been selected for further preclinical evaluation.

PMID- 15566303
TI  - Time-related differences in the physical property profiles of oral drugs.
AB  - Comparisons of the calculated physicochemical properties of oral drugs launched
      prior to 1983 (864 drugs) and between 1983 and 2002 (329 drugs) show that mean
      values of lipophilicity, percent polar surface area and H-bond donor count are
      the same, suggesting that these are the most important oral druglike physical
      properties. In contrast, mean values of molecular weight and the numbers of O + N
      atoms, H-bond acceptors, and rotatable bonds and rings have increased in 1983
      2002 drugs (by 13-29%). Analysis of the 1983-2002 oral drugs by therapy area
      shows that antiinfectives and nervous system drugs have the most extreme physical
      property profiles. Cardiovascular drugs show increasing molecular weight with
      year of publication, primarily a consequence of focusing on clinically proven
      mechanisms, with limited chemical diversity. Drug classes other than
      antiinfectives show comparable distributions of lipophilicity, suggesting that
      this property in oral drugs is important irrespective of the drug's target. The
      results suggest that the balance between polar and nonpolar drug properties is an
      important, unchanging feature of oral drug molecules.

PMID- 15566304
TI  - Design, synthesis, physicochemical properties, and evaluation of novel iron
      chelators with fluorescent sensors.
AB  - The synthesis of a range of novel 3-hydroxypyridin-4-ones and 3-hydroxypyran-4
      ones linked with different coumarin substituents is described. These compounds
      have been developed in order to provide a series of molecular probes for the
      quantification of intracellular labile iron pools. An evaluation of the effect of
      iron(III) on fluorescence intensity was undertaken. Chelation of iron(III) causes
      quenching of fluorescence. The relationship between iron(III) concentration and
      the extent of fluorescence quenching indicates that the metal is chelated in a
      complex with a metal-to-ligand stoichiometry of 1:3. The fluorescence of
      hydroxypyridinone compounds was found to be more efficiently quenched by
      iron(III) than were the hydroxypyranones. The metal-to-ligand stoichiometry at
      which maximum quenching is observed was found to depend on the site at which
      coumarin is attached. The efficiency of fluorescence quenching by iron(III) is
      markedly influenced by solvent polarity and pH. The permeability of two
      representative fluorescent chelators across human erythrocyte ghost membranes was
      investigated. The rate of permeability for a series of probes was found to be
      related to the corresponding ClogP values.

PMID- 15566305
TI  - Potent N-(1,3-thiazol-2-yl)pyridin-2-amine vascular endothelial growth factor
      receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low
      affinity for the hERG ion channel.
AB  - A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been
      developed that possess optimal properties. Compounds have been discovered that
      exhibit excellent in vivo potency. The particular challenges of overcoming hERG
      binding activity and QTc increases in vivo in addition to achieving good
      pharmacokinetics have been acomplished by discovering a unique class of amine
      substituents. These compounds have a favorable kinase selectivity profile that
      can be accentuated with appropriate substitution.

PMID- 15566306
TI  - Deriving knowledge through data mining high-throughput screening data.
AB  - Deriving general knowledge from high-throughput screening data is made difficult
      by the significant amount of noise, arising primarily from false positives, in
      the data. The paradigm established for screening an encoded combinatorial library
      on polymeric support, an ECLiPS library, has a significant amount of built-in
      redundancy. Because of this redundancy, the resulting data can be interpreted
      through a rigorous statistical analysis procedure, thereby significantly reducing
      the number of false positives. Here, we develop the statistical models used to
      analyze data from high-throughput screens of ECLiPS libraries to derive unbiased
      true hit rates. These hit rates can also be calculated on subsets of the
      collection such as those compounds containing a carboxylic acid or those with
      molecular weight below 350 Da. The relative value of the hit rate on the subset
      of the collection can then be compared to the overall hit rate to determine the
      effect of the substructure or physical property on the likelihood of a molecule
      having biological activity. Here, we show the effects that various functional
      groups and the standard physical properties, molecular weight, hydrogen bond
      donors, hydrogen bond acceptors, log P, and rotatable bonds, have on the
      likelihood of a compound being biologically active. To our knowledge this is the
      first published account of the use of high-throughput screening data to elucidate
      the effects of physical properties and substructures on the likelihood of
      compounds showing biological activity over a broad range of pharmaceutically
      relevant targets.

PMID- 15566307
TI  - Synthesis of tropeines and allosteric modulation of ionotropic glycine receptors.
AB  - Twenty esters of 3 alpha- and 3beta-hydroxy(nor)tropanes and two amides of 3
      alpha-aminotropane were prepared with substituted benzoic acids. These
      (nor)tropeines inhibited [(3)H]strychnine binding to glycine receptors in
      synaptosomal membranes of rat spinal cord. A ternary allosteric model was applied
      to determine the dissociation constants (K(A)) of the tropeines having strong
      negative cooperativities with [(3)H]strychnine binding (alpha > 10). K(A) values
      about 10 nM are well below those of known allosteric agents. Low concentrations
      (0.1K(A)) of the (nor)tropeines potentiated the displacing effects of glycine.
      Positive cooperativity with glycine (beta < 1) decreased with the increase in
      concentration and binding affinity of tropeines. Displacing potencies were also
      measured for [(3)H]granisetron binding to 5-HT(3) type serotonin receptors of rat
      cerebral cortex. Selectivities to glycine receptors versus 5-HT(3) receptors
      varied within 4 orders of magnitude. Nortropeines might serve as a lead to high
      affinity selective allosteric modulators of glycine receptors.

PMID- 15566308
TI  - New constrained "molecular tongs" designed to dissociate HIV-1 protease dimer.
AB  - New "molecular tongs" based on naphthalene and quinoline scaffolds linked to two
      peptidic strands were synthesized. They were designed to prevent dimerization of
      HIV-1 protease by targeting the antiparallel beta-sheet involving N- and C
      termini of each monomer. Compared to "molecular tongs" previously described
      (Bouras, A.; Boggetto, N.; Benatalah, Z.; de Rosny, E.; Sicsic, S.; Reboux
      Ravaud, M. J. Med. Chem. 1999, 42, 957-962), two main different structural
      features were introduced: positively charged quinoline as a new scaffold and two
      peptidic strands displaying different sequences. Seventeen new "molecular tongs"
      with dipeptidic or tripeptidic strands were synthesized. These molecules were
      assayed on HIV-1 protease using the Zhang kinetic technique. Eleven molecules
      behaved as pure dimerization inhibitors, mostly at the submicromolar range.
      Compared to a naphthalene scaffold, the quinoline one was shown in several cases
      to favor dimerization inhibition. The simplified hydrophobic Val-Leu-Val-OMe
      strand was confirmed as particularly favorable. The C-terminal analogue strand
      Thr-Leu-Asn-OMe was shown to be the best one for inducing dimerization inhibition
      (K(id) of 80 nM for compound 30). The mechanism of inhibition was ascertained
      using ANS binding and gel filtration. Experimental results are in agreement with
      the dissociation of the HIV-1 protease dimeric form in the presence of the
      synthesized molecular tongs.

PMID- 15566309
TI  - Monoamine transporter binding, locomotor activity, and drug discrimination
      properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester
      isomers.
AB  - The monoamine transporter binding properties, gross behavior, and locomotor
      activity effects in mice and drug discrimination results in cocaine-trained rats
      of the 2 beta,3beta-, 2 beta,3 alpha-, 2 alpha,3beta-, and 2 alpha,3 alpha
      isomers of several 3-(4-substituted-phenyl)tropane carboxylic acid methyl esters
      were compared (2a-f, 3a-f, 4a-f, and 5b,c). The 2 beta,3beta-isomer showed the
      highest affinity for the dopamine transporter (DAT), and the 2 beta,3 alpha
      isomer showed the next highest affinity. The order of potency for the 2
      beta,3beta-isomer is 4'-chloro (2c) = 4'-iodo (2e) > 4'-bromo (2d) = 4'-methyl
      (2f) > 4'-fluoro (2b) > 4'-hydrogen (2a). In the case of the 2 beta,3 alpha
      isomer, the order of affinity was 4'-bromo (3d) > 4'-iodo (3e) = 4'- chloro (3c)
      > 4'-methyl (3f) > 4'-fluoro (3b) > 4'-hydrogen (3a). The 4'-hydrogen, 4'-fluoro,
      and 4'-methyl 2 alpha,3beta-isomers, 4a, 4b, and 4f, had the lowest affinity for
      the DAT. While most of the compounds showed their highest affinity at the DAT,
      none were selective relative to the other two monoamine transporters. In general,
      the 2 alpha,3 alpha- and 2 alpha,3beta-isomers were more toxic (death and
      convulsions) than the 2 beta,3beta- and 2 beta,3 alpha-isomers. With the
      exception of the 2 alpha,3 alpha-isomers, all compounds produced the locomotor
      activity stimulation typical of dopaminergic drugs. The ED(50) ranges for the 2
      beta,3beta- (2a-f), 2 beta,3 alpha- (3a-f), and 2 alpha,3beta-isomers (4a-f) in
      the locomotor assay were 0.1-1.2, 6.6-21.8, and 2.4-11.7 mg/kg, respectively.
      With the exception of the 2 alpha,3 alpha-isomer, all compounds generalized to
      cocaine. The 2 beta,3beta-isomers were at least 10-fold more potent than cocaine
      and the other three sets of isomers in this test.

PMID- 15566310
TI  - Structure-activity relationships in platelet-activating factor. 12. Synthesis and
      biological evaluation of platelet-activating factor antagonists with anti-HIV-1
      activity.
AB  - The HIV-1 central nervous system infection leads to the onset of neurological
      impairments called AIDS dementia complex (ADC). PAF plays an important role in
      this pathology, as it is an HIV-1-induced neurotoxin produced by infected or
      activated macrophages and microglia, in the brain. We previously reported that
      PAF-antagonists bearing a trisubstituted piperazine presented in vitro anti-HIV-1
      activity in human macrophages. To improve the pharmacological activities of our
      lead compound, 1a, we modified its carbamate function and evaluated both its
      antiretroviral and anti-PAF activities. One carbamate derivative (10c)
      demonstrated a similar antiviral activity but a higher anti-PAF potency, whereas
      4a, with an ureide function, presents an increased antiviral activity and can be
      considered as a pure antiretroviral drug, as it does not present PAF-antagonism.
      Moreover, we measured the ability of 1a to cross the blood-brain barrier, using
      the in situ mouse brain perfusion method and its plasmatic concentrations after
      iv and po administration. The transport parameter measured (K(in)) proves that 1a
      is able to cross this biological barrier, but a pharmacokinetic study reveals its
      weak bioavailability in rats.

PMID- 15566311
TI  - Discovery of novel phenolic antioxidants as inhibitors of vascular cell adhesion
      molecule-1 expression for use in chronic inflammatory diseases.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to
      endothelial cells and is implicated in many inflammatory conditions. Since part
      of the signal transduction pathway that regulates the activation of VCAM-1
      expression is redox-sensitive, compounds with antioxidant properties may have
      inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been
      designed and synthesized starting from probucol (1). Many of these compounds
      demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and
      displayed potent antioxidant effects in vitro. Some of these derivatives (4o, 4p,
      4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro
      inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), and IL-6 from human peripheral blood mononuclear
      cells (hPBMCs) in a concentration-dependent manner in vitro and showed
      antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently
      in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention
      of chronic organ transplant rejection, respectively.

PMID- 15566312
TI  - Agents in development for prostate cancer prevention.
AB  - Accumulated epidemiological evidence indicates that prostate cancer mortality
      should be preventable. As androgenic hormones have long been recognised to be
      required for normal prostatic development, and because androgen deprivation is an
      established treatment for advanced prostate cancer, androgen signalling has been
      an attractive target for prostate cancer prevention. Inhibitors of 5alpha
      reductase, an enzyme necessary for the conversion of testosterone to the more
      potent androgen dihydrotestosterone, have reached pivotal clinical trials for
      prostate cancer prevention. In addition, new insights into the molecular
      pathogenesis of prostate cancer hint that chronic or recurrent prostate
      inflammation may contribute to the development of the disease. A variety of
      antioxidants and anti-inflammatory drugs, which are likely to be capable of
      attenuating pro-carcinogenic genome damage from reactive oxygen and nitrogen
      species, are also under current development for prostate cancer prevention. This
      review will consider the rational development of these and other new agents and
      approaches for prostate cancer prevention in the context of recent research
      progress in ascertaining the aetiology of prostate cancer.

PMID- 15566313
TI  - Systemic therapies for hepatocellular carcinoma.
AB  - For the minority of patients with hepatocellular carcinoma (HCC), surgical or
      locally ablative therapies may offer the prospect of cure. However, the majority
      of patients present with advanced disease such that treatment with curative
      intent is no longer possible. For some of these patients, with good hepatic
      reserve and a patent portal venous system, chemoembolisation may afford a modest
      survival benefit. The remainder of patients are frequently treated with systemic
      therapies with palliative intent. This review aims to summarise the current
      systemic treatment approaches for HCC in the adjuvant and palliative setting
      before reviewing the evidence for novel therapies emerging in this field. At
      present there are a number of interesting therapeutic agents with potential
      activity in HCC. The challenge now is the design of clinical trials to optimally
      evaluate these agents.

PMID- 15566314
TI  - The therapeutic potential of agents targeting the type I insulin-like growth
      factor receptor.
AB  - The type I insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine
      kinase that mediates insulin-like growth factor I (IGF-1) and IGF-2 signalling.
      Increased expression levels and/or enhanced activity of IGF-1R have been observed
      in many types of cancer. It is well documented that IGF-1R plays important roles
      in the proliferation, transformation, motility and metastasis of cancer cells.
      Therefore, IGF-1R has surfaced as an attractive target for cancer therapy. There
      are several aspects of this receptor that need to be considered when thinking
      about inhibitory strategies. In this review, several points relevant to targeting
      IGF-1R will be discussed, including the signalling pathways downstream of the
      receptor, the potential role for the insulin receptor in regulating IGF action
      and multiple cancer phenotypes regulated by this receptor. In addition, there are
      several strategies that could be used to inhibit IGF action. Inhibition of
      receptor function by lowering protein expression, decreasing kinase activity by
      small-molecule inhibitors, disrupting receptor function by monoclonal antibody
      blockade and neutralising circulating ligand all represent potential therapeutic
      strategies. As these strategies move forward to clinical trial, several important
      considerations need to be incorporated into the clinical trial design.

PMID- 15566315
TI  - Recent developments in the therapy of phaeochromocytoma.
AB  - The basic principles of treatment for phaeochromocytomas and paragangliomas are
      to block the effects of high catecholamines and make the patient safe for
      surgical removal of the tumour. The traditional preoperative medical preparation
      uses the non-selective alpha-adrenoceptor blocker phenoxybenzamine and a beta
      adrenoceptor blocker, propranolol. Other agents have been used effectively,
      including selective alpha-adrenoceptor blockers, doxazosin and prazosin, and
      calcium channel antagonists. There have been no trial comparing regimens and
      there is some controversy as to the best regimen. Major advances have been made
      in laparoscopic and laparoscopic-assisted surgery. Cortical-sparing adrenalectomy
      has been used in some centres for familial phaeochromocytomas. High-dose [(131)I]
      metaiodobenzylguanidine therapy and combined [(131)I]-metaiodobenzylguanidine and
      chemotherapy are promising new developments for the malignant disease. All
      patients should be followed indefinitely because the recurrence or malignancy
      rate is >or= 10% over a prolonged follow up.

PMID- 15566316
TI  - Metal-protein attenuating compounds and Alzheimer's disease.
AB  - Since the description of the amyloid plaque in the pathology of Alzheimer's
      disease, one of the main focuses of research has been the role of the amyloid
      precursor protein metabolite amyloid-beta, which is the constituent protein of
      plaque. Affecting the production, aggregation or clearance of this protein may
      well have a modifying effect on disease progression. Although available therapies
      for Alzheimer's disease may interact with amyloid-beta in vivo, no conspicuous
      disease-modifying effect has been demonstrated in clinical trials with these
      drugs. Drugs whose primary target is not the rectification of the
      neurotransmitter deficits associated with Alzheimer's disease but rather the life
      cycle of amyloid-beta are currently being developed with varying degrees of
      success. Of these drugs, the metal-protein attenuating compounds have currently
      the most encouraging clinical data supporting their use. Clioquinol is an example
      from this class, which has recently shown encouraging efficacy from early
      clinical evaluation in the absence of any compelling evidence of subacute
      myelopathic optic neuritis, which has been associated with this drug's use in
      Japanese populations. This article will discuss the scientific rationale behind
      the use of metal-protein attenuating compounds in Alzheimer's disease and
      summarise the available clinical trial data.

PMID- 15566317
TI  - Amyotrophic lateral sclerosis: contemporary concepts in etiopathogenesis and
      pharmacotherapy.
AB  - Among the neurodegenerative diseases associated with ageing, amyotrophic lateral
      sclerosis (ALS) remains the most devastating. The disease inexorably progresses,
      the vast majority of pharmacotherapies have failed to modify the disease course,
      death ensues on average within 5 years of symptom onset and increasing numbers of
      individuals are afflicted with the disease. However, significant advances in our
      understanding of the natural history of ALS and of the fundamental nature of the
      biological defect underlying motor neuron degeneration have been gained,
      providing hope for the development of novel pharmacotherapies for ALS. Among
      these is the recognition that ALS is a biologically heterogeneous disorder in
      which genetics, environment and ageing all interrelate. The observation of
      clinical heterogeneity, with initial clinical manifestations serving as
      predictors of survivorship, is of considerable importance in designing
      therapeutic trials. The presence of frontotemporal dysfunction in a subset of
      patients has led to increased interest in the relationship between ALS and the
      degenerative tauopathies. Ultimately, the degenerating motor neurons do not die
      alone. The contribution of both microglia and astrocytes to the degenerative
      process are increasingly recognised. Understanding how these processes
      interrelate has become critical to understanding the pharmacotherapy of ALS and
      in the design of clinical trials. This review will highlight recent
      epidemiological and neurochemical advances in our understanding of ALS, and place
      them into the context of understanding the development of novel treatment avenues
      for this devastating disease.

PMID- 15566318
TI  - Novel therapies for the prevention of stroke.
AB  - The health and economic burden of stroke to society is enormous. Pharmacological
      therapies remain the primary stroke prevention strategy for the vast majority.
      Several existing and newer pharmacological agents aimed at the treatment of
      hypertension and lowering cholesterol are proving to be effective. For example,
      the antiplatelet agent clopidogrel has reduced end points in the secondary
      prevention of stroke, as have combinations of aspirin with traditional therapies,
      including dipyramidole. The direct oral thrombin inhibitor ximelagatran is a
      novel oral anticoagulant that has shown significant potential as a possible
      replacement to warfarin therapy, for the prevention of stroke for patients with
      non-valvular atrial fibrillation. Additional novel agents with hypothetical,
      although not yet proven, benefits in stroke prevention include fish oils,
      homocysteine-lowering therapy and anti-inflammatory agents. Finally, a
      controversial novel polypill, which would include fixed combinations of several
      pharmacological agents, may yet become a realistic and promising stroke
      prevention option.

PMID- 15566319
TI  - Atrasentan: targeting the endothelin axis in prostate cancer.
AB  - Endothelin axis deregulation triggers a series of events that lead to a profound
      deregulation in cancer cells, including key tumorigenic cellular events such as
      proliferation, invasion, escape from programmed cell death, new vessel formation,
      abnormal osteogenesis and the alteration of nociceptive stimuli. Atrasentan is a
      novel agent that effectively targets this pathway and is able to inhibit and/or
      reverse several of those events. Biological and clinical activity in patients
      with prostate cancer has been demonstrated in a Phase III clinical setting by the
      suppression of markers of biochemical and clinical prostate cancer progression,
      and by a delay in time to disease progression, especially in patients with bone
      disease.

PMID- 15566320
TI  - Alpha-lipoic acid, an anti-obesity agent?
AB  - Obesity shortens life expectancy and is a risk factor for hypertension and Type 2
      diabetes. When added to the standard chow of Sprague-Dawley or Otsuka Long-Evans
      Tokushima Fatty rats, alpha-lipoic acid (0.5% weight/weight) reduced body weight
      and food intake. Alpha-lipoic acid also increased whole-body energy expenditure.
      It exerts its effects by suppressing hypothalamic AMP-activated protein kinase.
      Long-term studies to determine whether these anti-obesity effects are maintained
      in animals are required before alpha-lipoic acid is considered for clinical trial
      in human obesity.

PMID- 15566321
TI  - Cancer immunotherapeutics meeting.
AB  - The annual meeting of Cancer Immunotherapeutics held in Boston integrated a multi
      disciplinary audience of scientists from academia and biotech companies, as well
      as venture capitalists, in an attempt to bring to the forefront the most thought
      provoking approaches toward cancer immunotherapy as well as innovations in
      biotechnologies. The major focus of the meeting was to bring together
      investigators to discuss technologies that can enhance immune responsiveness.
      Major themes included the enhancement of T-cell recognition and killing by the
      addition of cytokines or through novel inhibitors of in vitro cell signalling
      factors. Many of the presentations were based on studies that may provide the
      groundwork for translation into the clinic. Another goal of this meeting was to
      foster collaborations among investigators to facilitate and extend current
      research objectives.

PMID- 15566322
TI  - Ion channels in drug discovery and development.
AB  - An excellent meeting on ion channels in drug discovery and development was
      organised by the Strategic Research Institute. Recent progress in the molecular
      and cellular biology of ion channels, their localisation and their physio
      pathological roles, was presented by a selected number of academic researchers.
      The status of development, by pharmaceutical companies, of drugs targeting
      specific ion channel subtypes (e.g., AMPA receptors, nicotinic receptors, GABA(A)
      receptors, K(+) channels, transient receptor potential channels) and with
      different modalities (agonists versus potentiators) was reviewed. More
      comparative data on the emerging ion channel screening technologies are now
      available and were shared in a number of presentations. Finally, cardiac ion
      channel liability, in the context of drug discovery and development, was
      thoroughly discussed.

PMID- 15566323
TI  - Phage therapy: where East meets West.

PMID- 15566324
TI  - Impact of HIV infection and antiretroviral therapy in the older patient.

PMID- 15566325
TI  - New once-daily HIV combination better tolerated.

PMID- 15566328
TI  - Gemifloxacin: a new, potent fluoroquinolone for the therapy of lower respiratory
      tract infections.
AB  - The fluoroquinolone gemifloxacin has recently been approved for the treatment of
      acute bacterial exacerbations of chronic bronchitis and mild community acquired
      pneumonia, including that caused by multidrug-resistant Streptococcus pneumoniae.
      Owing to the increasing prevalence of multidrug-resistant S. pneumoniae, as well
      as resistance to other common pathogens of acute bacterial exacerbations of
      chronic bronchitis and community acquired pneumonia, it is important to have new,
      potent antimicrobial agents for the treatment of these infections. Gemifloxacin
      is the most potent antimicrobial agent in vitro for S. pneumoniae, and has
      excellent activity against the other key pathogens of acute bacterial
      exacerbations of chronic bronchitis and community acquired pneumonia, including
      the atypical microorganisms. The clinical trial outcomes of several studies that
      have evaluated gemifloxacin show a range of superior clinical or bacteriologic
      outcomes against several current antimicrobials, including levofloxacin,
      clarithromycin, trovafloxacin and ceftriaxone. The safety profile of gemifloxacin
      is similar to that of approved agents to treat acute bacterial exacerbations of
      chronic bronchitis and community acquired pneumonia, with a low discontinuation
      rate of 2.2%. A nonphototoxic rash (usually a mild, maculopapular rash) was
      observed in 2.8% of patients in clinical studies.

PMID- 15566329
TI  - Dalbavancin: an investigational glycopeptide.
AB  - Glycopeptide antimicrobials have been a component of our therapeutic
      armamentarium for nearly 50 years. Although vancomycin, and more recently
      teicoplanin, have performed yeoman service over the years, the specter of
      bacterial resistance among Gram-positive aerobes has created doubts concerning
      how long they will continue to be useful antimicrobial agents. In an attempt to
      prolong the utility of the glycopeptides, efforts are underway to create new
      derivatives with improved pharmacologic and pharmacokinetic properties. One
      example of an improved glycopeptide from the pharmacokinetic perspective is
      dalbavancin (BI397)--a teicoplanin analog currently undergoing human testing.
      Elimination of this compound from the body occurs extremely slowly, with terminal
      disposition half-lifes of up to 200 h in healthy volunteers, thus allowing once
      weekly dosing. Although not generally considered to be a potential alternative
      for the treatment of infections due to glycopeptide-resistant Gram-positive
      pathogens, dalbavancin may still be considered an advance on existing agents
      based on its patient-convenient once-weekly dosing regimen.

PMID- 15566330
TI  - Entecavir for the treatment of chronic hepatitis B.
AB  - Chronic infection with the hepatitis B virus remains a serious and life
      threatening disease for approximately 5% of the world's population, despite the
      availability of effective vaccines. Although prognoses can be improved by
      chemotherapy, treatment options are limited and none has been consistently
      successful. Interferon-alpha, the longest established therapy, has limited
      efficacy, is slow-acting and frequently causes adverse effects. Newer drugs
      comprise of mainly nucleoside and nucleotide analogs. The two that are currently
      approved, lamivudine and adefovir dipivoxil, are well tolerated; both produce
      rapid and dramatic responses, but their effects may not be sustainable in the
      long-term due to the emergence of resistant virus. Development of resistance to
      lamivudine is approximately ten-times more frequent than development of
      resistance to adefovir dipivoxil (approximately 60 and 6%, respectively) during
      the first 3 years of therapy. Entecavir, a carbocyclic deoxyguanosine analog that
      is active against both lamivudine- and adefovir dipivoxil-resistant HBV, is in
      the vanguard of new antihepatitis B virus drugs that have progressed to Phase III
      clinical trials. It is the most potent antihepatitis B virus agent discovered to
      date.

PMID- 15566331
TI  - Advances in screening test development for transmissible spongiform
      encephalopathies.
AB  - The blood of patients with transmissible spongiform encephalopathy or prion
      disease can no longer be considered free of infectivity. There have been two
      recent reports of highly probable transfusion-associated iatrogenic variant
      Creutzfeldt-Jakob disease infections, and there is supporting experimental
      evidence of scrapie transmission by the transfusion of blood from sheep with
      naturally occurring disease. In the absence of a preclinical diagnostic test for
      transmissible spongiform encephalopathy, the main precautionary measures
      undertaken by blood agencies employ donor exclusion criteria, ensuring that the
      number of any further iatrogenic cases will be small. The development of a
      sensitive, specific and reliable diagnostic test is urgently needed for early
      identification of infected individuals in order to ensure the safety of blood
      supplies. During the past 5 years, significant progress has been made in
      improving the sensitivity and specificity of tests using brain and
      lymphoreticular tissues to identify Creutzfeldt-Jakob disease-infected
      individuals. However, the quest for a blood test is still in its infancy and
      requires extensive further research.

PMID- 15566332
TI  - Epidemiology, pathogenesis and prevention of congenital cytomegalovirus
      infection.
AB  - Cytomegalovirus is the most common cause of congenital infection. Congenital
      cytomegalovirus infection can follow both primary and recurrent maternal
      infections. It is associated with a significant burden of disease and death. The
      determinants of mother-to-child transmission and the pathogenesis of symptomatic
      fetal infection remain poorly understood. For a long time, congenital
      cytomegalovirus infection has been a neglected disease. Recently, the Institute
      of Medicine has recognized that the development of a vaccine against congenital
      cytomegalovirus infection is a public health priority, which should stimulate
      research in this area. The development of antiviral therapies to prevent symptoms
      in infected newborns also represents an important area of research.

PMID- 15566333
TI  - Dengue vaccine: priorities and progress.
AB  - Dengue transmission has increased considerably in the past 20 years. Currently,
      it can only be reduced by mosquito control; however, the application of vector
      control methods are labor intensive, require discipline and diligence, and are
      hard to sustain. In this context, a safe dengue vaccine that confers long-lasting
      protection against infection with the four dengue viruses is urgently required.
      This review will discuss the requirements of a dengue vaccine, problems, and
      advances that have been made. Finally, new targets for research will be
      presented.

PMID- 15566334
TI  - Evolving issues in understanding and treating bacterial vaginosis.
AB  - Bacterial vaginosis is a synergistic polymicrobial syndrome characterized by
      depletion of Lactobacillus spp., especially those that produce hydrogen peroxide,
      and an intense increase in the quantity of commensal vaginal anaerobic bacteria
      to 100- to 1000-fold above normal levels. While the bacterial spectrum of these
      organisms has long been known to include Gardnerella vaginalis, Prevotella spp.,
      anaerobic Gram-positive cocci, Mobiluncus spp. and Mycoplasma hominis, innovative
      use of molecular diagnostics has identified novel species apparently associated
      with this syndrome, including Atopobium vaginalis. Effecting resolution of
      bacterial vaginosis is important, in particular for the 8 to 23% of women
      afflicted with symptomatic disease during their reproductive years. Bacterial
      vaginosis has been consistently associated with numerous adverse sequelae related
      to the upper genital tract, including pelvic inflammatory disease and
      postsurgical infection in the setting of invasive gynecologic procedures, and may
      increase women's risk of acquiring HIV infection. Pregnant women with bacterial
      vaginosis experience a higher rate of preterm delivery and low-birth-weight
      infants. While antibiotics with activity against anaerobes--typically,
      metronidazole and clindamycin applied vaginally or taken orally--are the
      mainstays of therapy, bacterial vaginosis frequently recurs. For these reasons,
      innovative approaches to therapy are urgently required.

PMID- 15566335
TI  - Antibiotic treatment for urinary tract infections:
      pharmacokinetic/pharmacodynamic principles.
AB  - Bacterial urinary tract infections (UTIs) frequently occur in the outpatient as
      well as in the nosocomial setting. The stratification into uncomplicated and
      complicated UTIs has proven to be clinically useful. Bacterial virulence factors
      on the one hand, and the integrity of the host defense mechanisms on the other,
      determine the course of the infection. Late complications or sequelae might ensue
      if the defense mechanisms are disturbed, either by a genetic or an acquired
      cause. Escherichia coli is the most prevalent organism in uncomplicated UTIs,
      whereas the bacterial spectrum is much broader in complicated UTIs, including
      Gram-negative and -positive, and often multiresistant organisms. Therapy for
      uncomplicated UTIs is almost exclusively antibacterial, whereas in complicated
      UTIs the complicating factors need to be treated as well. The success of
      antibiotic therapy of UTIs in a population can be estimated by four parameters:
      the minimal inhibitory concentrations of the clinical isolates, the
      pharmacokinetic and pharmacodynamic profiles, and the protein binding of the
      treatment drug. In uncomplicated UTIs, antimicrobial therapy is usually empiric,
      whereas in complicated UTIs antibiotic therapy should be more individualized;
      tailored to the individual patient.

PMID- 15566336
TI  - Group counseling for mothers after emergency cesarean section: a randomized
      controlled trial of intervention.
AB  - BACKGROUND: An emergency cesarean section is often a traumatic experience for
      women, and can be associated with postnatal depression and posttraumatic stress.
      Various types of interventions have been tested to prevent such consequences. The
      purpose of this study was to test a model of group counseling for mothers after
      emergency cesarean section, and to examine its possible effects. METHOD: After
      undergoing an emergency cesarean section, 162 Swedish-speaking women were
      randomized to group counseling or the control group. The participation rate was
      75 percent. The counseling consisted of 2 sessions, conducted at about 2 months
      postpartum; 72 percent of the women randomized to the counseling group actually
      attended the sessions. At 6 months postpartum, all study participants completed a
      postal questionnaire (response rates were 92% in the counseling group and 89% in
      the control group). RESULTS: No difference between the groups was found in terms
      of the level of fear after childbirth, symptoms of posttraumatic stress, or
      postnatal depression at 6 months after the emergency cesarean. The group
      counseling was much appreciated by the participating women, some of whose
      experiences are reported in this paper. CONCLUSION: Group counseling for mothers
      after emergency cesarean section did not influence their views on the recent
      delivery or prevent symptoms of posttraumatic stress or postnatal depression. It
      was, however, appreciated and did no harm. In future studies, other outcomes
      should be measured.

PMID- 15566337
TI  - Effect of managed care enrollment on primary and repeat cesarean rates among U.S.
      Department of Defense health care beneficiaries in military and civilian
      hospitals worldwide, 1999-2002.
AB  - BACKGROUND: In response to rising cesarean rates, it is reasonable for health
      care organizations to look to a managed care model as a means of controlling
      further rate increases. However, little conclusive evidence exists to support
      this solution. We undertook a study of the Department of Defense health care
      beneficiary population to assess the impact of enrollment in TRICARE Prime, the
      Department's managed care health plan, on cesarean delivery rates. METHODS:
      Pooled hospital discharge records from 1999-2002 for live, singleton births were
      analyzed to calculate primary and repeat cesarean rates for TRICARE Prime and non
      Prime beneficiaries in the military and civilian hospitals that comprise the
      Department of Defense health care network. Stepwise logistic regression was used
      to calculate adjusted odds ratios for clinical indicators for each combination of
      health plan and hospital setting using the chi2 difference(p <0.05)to eliminate
      nonsignificant variables from the model. Total primary and repeat cesarean rates
      were compared with primary and repeat cesarean rates for women with no reported
      clinical complications to account for differences in case mix across subgroups.
      Statistical significance of the differences calculated for subgroups was assessed
      using chi2. RESULTS: Primary cesarean rates were significantly lower for TRICARE
      Prime enrollees relative to non-Prime beneficiaries for all race subgroups and
      three of five age subgroups in military hospitals and four of five age subgroups
      in civilian hospitals. No significant differences in repeat cesarean rates were
      observed between Prime and non-Prime beneficiaries within any race or age
      subgroup. Breech presentation followed by dystocia, fetal distress, and other
      complications were significant predictors for primary cesarean. Previous cesarean
      delivery was the leading predictor for repeat cesarean delivery. Primary and
      repeat cesarean rates observed for military hospitals were consistently lower
      than rates observed for civilian hospitals within each health plan type and age
      group. CONCLUSIONS: Enrollment in the managed care health plan was significantly
      associated with lower risk of primary cesarean delivery relative to membership in
      other health plans offered to Department of Defense health care beneficiaries.
      Repeat cesarean rates in this population varied independently of health plan
      type. Primary cesarean delivery was generally associated with clinical
      complications, whereas previous cesarean delivery was the strongest indicator for
      a repeat cesarean delivery. A clear explanation of reduced cesarean rates for
      Prime enrollees remains elusive, but it is likely that factors beyond individual
      practitioner decision-making were at work.

PMID- 15566338
TI  - Influence of knowledge and attitudes on exclusive breastfeeding practice among
      rural Jamaican mothers.
AB  - BACKGROUND: A large number of mothers may not be practicing exclusive
      breastfeeding in rural Jamaica, although no recent systematic study has been
      conducted. The impact of knowledge about and attitude toward breastfeeding on the
      duration of exclusive breastfeeding is also poorly understood. The objective of
      this study was to gather information about factors that influence exclusive
      breastfeeding and its duration. METHOD: A cross-sectional study was conducted in
      11 health centers within the parish of Saint Ann, Jamaica. A pretested
      questionnaire collected information on breastfeeding knowledge and attitudes
      toward intention to breastfeed and other relevant sociodemographic
      characteristics. RESULTS: Information was documented for 599 mother-child pairs.
      The prevalence of breastfeeding initiation was 98.2 percent; of mothers who
      initiated breastfeeding, 22.2 percent practiced it exclusively (at least 6
      months). No difference occurred between exclusive and nonexclusive breastfeeding
      mothers in terms of knowledge about and attitudes toward breastfeeding. Of
      potential predictors assessed, the male partner's role as the main source of
      income for the family was the only significant predictor for exclusive
      breastfeeding. Women whose male partner was the main source of income for the
      family were twice as likely to exclusively breastfeed their infants compared with
      the referent group (mothers as main source of income)(OR=2.0; 95% CI=1.4-3.0). In
      addition, the dominant reason for partial breastfeeding was maternal anxiety that
      breastmilk alone might not provide sufficient nourishment. CONCLUSION: The level
      of exclusive breastfeeding was extremely low at the study site. Formulation of
      strategies to aggressively promote exclusive breastfeeding practices is urgently
      needed there. Such interventions should consider involvement of the male partner,
      especially, with respect to the financial support, as well as alleviating
      maternal anxiety regarding nutritional adequacy of breastmilk.

PMID- 15566339
TI  - What factors are associated with parents' desire to know the sex of their unborn
      child?
AB  - BACKGROUND: Parents feel strongly about whether or not to learn the sex of their
      fetus. We sought to determine which factors are significantly associated with
      parents' desire to know or not to know the fetal sex during a prenatal
      ultrasound. METHODS: All women undergoing prenatal ultrasound examinations,
      except for those with suspected failed pregnancies, were invited to answer a
      questionnaire at an outpatient referral center for diagnostic ultrasound in
      obstetrics and gynecology in Boston, Massachusetts. The survey asked about
      demographic factors, current pregnancy, and past pregnancies, and an open-ended
      question about whether and why the parents wished to learn, or did not learn, the
      sex of their fetus. Factors significantly associated with parents' desire to
      learn the fetal sex prenatally were determined and analyzed. RESULTS: A total of
      1,340 questionnaires were completed. Overall, 761/1,302 (58%) of mothers and
      747/1,295 (58%) of fathers learned or planned to learn the fetal sex before
      delivery. Factors most associated with wanting to learn the fetal sex were
      conceiving accidentally, finding out the sex in a previous pregnancy, not
      planning to breastfeed, influence of sex on future childbearing plans, planning a
      move or renovation dependent on sex, and specific parental sex preference.
      Demographic factors most associated with wanting to learn the fetal sex were
      father without full-time job, lower household income, unwed mother, maternal age
      less than 22 or greater than 40 years, no college degree, race other than white,
      and religion other than Catholic. CONCLUSIONS: Specific demographic and
      socioeconomic characteristics predicted whether or not parents chose to know the
      sex of their unborn child. Families in which the pregnancy was unplanned, those
      in which fetal sex would influence living arrangements or future childbearing
      plans, and those of lower socioeconomic status wished to know the sex more
      frequently. Further study is needed to understand parents' motivations underlying
      the desire to know or not know fetal sex before delivery.

PMID- 15566340
TI  - Physicians' responses to patient-requested cesarean delivery.
AB  - BACKGROUND: The issue about whether a woman's autonomy in childbirth should
      include the choice of cesarean delivery in the absence of medical indications has
      become a major source of debate. Our objective was to examine factors that
      determined physicians' responses to patient-requested cesarean delivery. METHODS:
      Surveys were distributed to all obstetrician-gynecologists in the greater
      Portland, Oregon, metropolitan area in Spring, 2000. Physicians were asked to
      respond to scenarios involving a term patient with a singleton pregnancy
      requesting primary cesarean delivery. RESULTS: One hundred and seventy of 255
      physicians (67%) responded, of whom 68 to 98 percent agreed to cesarean delivery
      in cases with clear medical indications. Without a clear medical indication, most
      practitioners would not perform a cesarean delivery. In cases where medical
      indications were unclear, responses were divided. Physician male gender and
      patient high socioeconomic status were associated with increased likelihood of
      physician agreement to patient-requested cesarean delivery. Age, years in
      practice, and practice type were not associated with agreement. CONCLUSIONS:
      Physicians are reluctant to agree to patient request for primary cesarean
      delivery without a clear medical indication. Male physicians were more likely to
      agree to a patient's request for cesarean delivery than female physicians.

PMID- 15566341
TI  - Incidence and duration of breastfeeding for term infants in Canada, United
      States, Europe, and Australia: a literature review.
AB  - BACKGROUND: Analysis of differences in the incidence and duration of
      breastfeeding across countries may provide information about practices that
      encourage breastfeeding. This comparative review examines variation in the
      incidence and duration of breastfeeding for term infants that has been reported
      in studies from Canada, the United States, Europe, and Australia. METHODS:
      Searches were conducted in PubMed, MEDLINE (from 1966), CINHAL (from 1982), and
      the Cochrane Database of Systematic Reviews. Studies were limited to
      nonexperimental and observational research that addressed term infants (>37 weeks
      gestational age), performed in developed countries, written in the English
      language, and published since 1990. Additional studies were located from
      reference lists of meta-analyses, systematic reviews, and previous articles. All
      studies that met study criteria were included in the review, regardless of the
      quality of methodology. RESULTS: Although studies had methodological limitations
      that precluded conducting a formal systematic review or meta-analysis, this
      comparative review revealed consistent differences among countries. For example,
      Europe and Australia reported a higher initiation and duration of breastfeeding
      term infants compared with Canada and the United States. CONCLUSIONS: Studies
      that examined reasons for a higher incidence and duration of breastfeeding term
      infants consistently document that women who initiate and continue to breastfeed
      are older, married, better educated, and have higher family incomes than women
      who do not breastfeed.

PMID- 15566342
TI  - Changing the use of electronic fetal monitoring and labor support: a case study
      of barriers and facilitators.
AB  - BACKGROUND: Decreasing the use of continuous electronic fetal monitoring and
      increasing professional labor support for low-risk pregnancies are recommended by
      the Society of Obstetricians and Gynecologists of Canada. This study explored
      factors influencing the successful (and unsuccessful) introduction of an evidence
      based fetal health surveillance guideline. METHODS: This qualitative case study
      was conducted at two tertiary and one community hospital. Data were collected in
      14 clinician focus groups (51 nurses), followed by 8 interviews with nurse
      administrators and educators. Analysis of verbatim transcripts and unit records
      included coding and categorizing data to form profiles that were compared across
      hospitals. RESULTS: Implementation of the guideline recommendations in the
      hospital settings was affected by many different factors originating in the
      practice environment, with the potential adopters, and related to the
      characteristics of the guideline. The influences of these diverse factors
      interacted sometimes to magnify or counteract each other's effect. The physical
      setting, adopter concerns, and the medicolegal issues surrounding the guideline
      played critical roles in uptake. In addition, changes preceding the introduction
      of the recommendations, the institution's agenda, and nursing and medical
      leadership influenced the uptake of guideline recommendations. The number and
      experience of nurses in each setting and availability of equipment also affected
      guideline acceptance and use. CONCLUSIONS: When implementing best practice, it is
      important to identify organizational barriers to the change that will need
      managing by the appropriate level of administration in the organization. Careful
      tailoring of implementation interventions to the barriers originating with the
      potential adopters is also necessary. Be prepared for unanticipated effects.

PMID- 15566343
TI  - Effect of a training program for maternity ward professionals on duration of
      breastfeeding.
AB  - BACKGROUND: Training programs are commonly viewed as an effective way to improve
      breastfeeding-related practices of health professionals. The objective of this
      study was to determine whether a 3-day training program for maternity ward
      professionals was followed by an increase in duration of any breastfeeding.
      METHODS: A before-and-after study was conducted involving two retrospective
      random samples of 308 mothers who had delivered a healthy singleton infant of 37
      weeks' or more gestation and 2,500 g or more birthweight in a level 3 maternity
      ward in a university hospital in France. Data were gathered from medical records
      and postal questionnaire. RESULTS: Study participants included 169 mothers
      (54.9%) in the pre-intervention sample and 178 (57.8%) in the post-intervention
      sample. The prevalence of any breastfeeding at birth was 77.5 percent (70.5%
      83.6%) in the pre-intervention sample and 82.6 percent (76.2%-87.8%) in the post
      intervention sample(p=0.24); the median duration of any breastfeeding was 13
      weeks and 16 weeks, respectively(chi2 log-rank test=5.8, p=0.02). The decreased
      risk of weaning in the post-intervention sample persisted after adjustment for
      baseline characteristics (adjusted hazard ratio=0.70 [0.54-0.91]). It was
      paralleled by significant improvement in maternity ward practices that are known
      to affect the duration of breastfeeding. CONCLUSION: An intensive 3-day training
      program for maternity ward professionals can be followed by a significant but
      moderate increase in the duration of any breastfeeding. Multifaceted
      interventions involving prenatal components and community support should be
      planned in Western countries with low to intermediate prevalence of
      breastfeeding.

PMID- 15566344
TI  - Humanizing birth: a global grassroots movement.
AB  - A survey of a convenience sample of 24 grassroots birth activist groups based in
      several countries revealed remarkable similarities despite differences in culture
      and maternity care systems. With few exceptions, they began with a few
      individuals, generally women, who were dissatisfied or angry with an obstetric
      management system that failed to provide safe, effective, humane maternity care,
      that suppressed alternative models of care and nonconforming practitioners, or
      both. Responses indicated that organizational structures tend to fall into a
      limited number of categories, and strategies intended to accomplish reform
      overlap considerably. All groups have experienced difficulties resulting from the
      hegemony of conventional obstetric management and active opposition of
      practitioners within that model. Most groups are volunteer based, and all
      struggle under the handicap of limited resources compared with the forces arrayed
      against them and the scope of what they hope to accomplish.

PMID- 15566345
TI  - "O brave new world!".

PMID- 15566349
TI  - Alemtuzumab therapy for refractory idiopathic hypereosinophilic syndrome with
      abnormal T cells: a case report.

PMID- 15566350
TI  - Vacuolated neutrophils in ethanol toxicity.

PMID- 15566351
TI  - Genetic polymorphisms predicting the outcome of bone marrow transplants.
AB  - Analysis of non-histocompatibility leucocyte antigen (HLA) functional genomics,
      together with conventional risk factors in haematopoietic stem cell
      transplantation (HSCT) can lead to predicting outcome in HLA-matched sibling
      transplant recipients. Polymorphisms of cytokine genes including tumour necrosis
      factor alpha, interleukin-10, interferon gamma and interleukin (IL)-6, associate
      with more severe acute graft-versus-host disease (aGvHD). Donor genotype for IL-1
      receptor antagonist (IL-1Ra) has been associated with reduced aGvHD severity.
      Other genotypes (patient IL-1Ra, IL-6 and donor IL-1 alpha) have been associated
      with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen
      receptor). Polymorphisms within genes associated with host defence/inflammatory
      responses (mannose binding lectin genes, myeloperoxidase genes and the FC gamma
      receptors) have been associated with infections. Polymorphisms of pharmacogenes,
      such as methylenetetrahydrofolate-reductase, have been associated with aGvHD and
      other post-transplant complications. The NOD2 gene polymorphism, associated with
      Crohn's disease, has been shown to be associated with risk of gut GvHD. The
      majority of the studies have been carried out in single centre HLA-matched
      sibling cohorts and in relatively few matched unrelated donor transplants. This
      review gives an overall perspective of the current field of non-HLA genetics with
      regard to HSCT outcome, clinical relevance and potential application of the
      results to clinical management of HSCT.

PMID- 15566352
TI  - Bleeding and bruising in patients with Ehlers-Danlos syndrome and other collagen
      vascular disorders.
AB  - Easy bruising and bleeding are not only characteristic manifestations of clotting
      and platelet disorders, they are also prominent features in some heritable
      collagen disorders, such as the Ehlers-Danlos syndromes (EDS). The EDS comprise a
      heterogeneous group of connective tissue diseases sharing clinical manifestations
      in skin, ligaments and joints, blood vessels and internal organs. Most EDS
      subtypes are caused by mutations in genes encoding the fibrillar collagens type
      I, III and V, or in genes coding for enzymes involved in the post-translational
      modification of these collagens. Easy bruising is, to a variable degree, present
      in all subtypes of EDS, and is because of fragility of the capillaries and the
      perivascular connective tissues. Vascular fragility affecting medium-sized and
      large arteries and veins is typically observed in the vascular subtype of EDS,
      caused by a molecular defect in collagen type III, an important constituent of
      blood vessel walls and hollow organs. Extensive bruising, spontaneous arterial
      rupture, leading to severe internal bleeding or premature death, and rupture of
      hollow organs, such as the intestine or the gravid uterus are predominant
      features of this subtype. Haematological studies including evaluation of clotting
      factors, platelet aggregation and bleeding time are usually normal in patients
      with EDS, except for the Hess test (Rumple-Leede test), which may be abnormal,
      indicating capillary fragility. In some forms of EDS confirmation of the clinical
      diagnosis and subtype is possible with biochemical and molecular studies.

PMID- 15566353
TI  - The role of granulocyte transfusions in neutropenic patients.
AB  - The precise role for donor granulocyte infusions remains to be delineated, partly
      because of the lack of defined clinical trials. The aim of this article is to
      summarize the studies undertaken so far and highlight the logistical problems
      associated with undertaking future studies. We also aim to provide a practical
      guide to the application of this therapeutic approach.

PMID- 15566354
TI  - Characterization of the imprinted polycomb gene L3MBTL, a candidate 20q tumour
      suppressor gene, in patients with myeloid malignancies.
AB  - Chromosome 20q deletion is a recurrent chromosomal abnormality associated with
      myeloid malignancies. L3MBTL represents a strong candidate tumour suppressor gene
      since it lies within the common deleted region, is a member of the Polycomb-like
      family, encodes the human homologue of a Drosophila tumour suppressor and is
      expressed within haematopoietic progenitor cells. We describe the structure of
      L3MBTL, identify two putative promoters each associated with two CpG islands and
      characterize a complex pattern of alternative splicing events. Mutation analysis
      of the gene in patients with and without a 20q deletion identified several
      polymorphisms but no acquired mutations. The two CpG islands spanning promoter 2
      undergo monoallelic methylation in normal haematopoietic cells consistent with
      imprinting of L3MBTL. Samples from patients with a 20q deletion retained either
      the methylated or unmethylated allele but retention of the methylated allele did
      not correlate with reduction in L3MBTL mRNA levels. The absence of a correlation
      between L3MBTL methylation and transcription could be shown to reflect loss of
      imprinting in one patient. In addition, our results demonstrate that inactivation
      of L3MBTL is not a common occurrence in patients with a 20q deletion or in
      cytogenetically normal patients with polycythaemia vera.

PMID- 15566355
TI  - Pro-apoptotic therapy with the oligonucleotide Genasense (oblimersen sodium)
      targeting Bcl-2 protein expression enhances the biological anti-tumour activity
      of rituximab.
AB  - New strategies have evolved in the treatment of patients with non-Hodgkin's
      lymphoma (NHL). Anti-sense oligonucleotides (ASO) and monoclonal antibody (mAb)
      therapy, though proven to be safe and effective, have not demonstrated to be
      curative when used as single agents. We tested an innovative combination strategy
      involving various mAbs and ASO against Bcl-2 (G3139) in aggressive preclinical
      models. G3139, under optimal transfection conditions, decreased the proliferation
      rate of lymphoma cells by 60-75% when compared with controls. In addition,
      apoptosis was demonstrated in Raji (25%) and DHL-4 cells (30%) treated with
      Genasense following downregulation of Bcl-2 protein. Downregulation of Bcl-2 by
      G3139 was associated with a higher degree of rituximab-associated, complement
      mediated cytotoxicity and antibody dependent cellular cytotoxicity when compared
      with rituximab alone-treated controls. In vivo studies in severe combined
      immunodeficiency (SCID) mice clearly demonstrated synergistic activity between
      G3139 and rituximab. Treatment of lymphoma-bearing SCID mice with G3139 for two
      consecutive days prior to each rituximab dose resulted in better disease control
      and survival than treatment with either agent alone or controls. Our findings
      suggest that Bcl-2 downregulation by G3139, followed by the administration of
      rituximab is an efficient anti-tumour strategy associated with improved survival
      in lymphoma-bearing SCID mice.

PMID- 15566356
TI  - Effect of IL-2R beta-binding cytokines on costimulatory properties of chronic
      lymphocytic leukaemia cells: implications for immunotherapy.
AB  - Weak immunogenicity of chronic lymphocytic leukaemia (CLL) cells may contribute
      to disease progression and inhibit the effectiveness of immunotherapies, such as
      vaccines. Agents that can enhance the antigen presenting capabilities of CLL
      cells might then help to improve the clinical results of immunotherapies. This
      study investigated the effects of the common gamma chain-binding cytokines,
      interleukin (IL)-2 and IL-15, on costimulatory properties of primary CLL cells
      from 51 patients. IL-2 improved the ability of CLL cells to stimulate T cell
      proliferation and increased the expression of costimulatory molecules
      (particularly CD80) in a dose-dependent fashion, especially in CLL cells with
      weak expression of CD38. CD80 and CD86 induction by IL-2 were positively
      regulated through the mitogen-activated protein kinase pathway, while CD86
      expression was negatively regulated through Janus kinase pathways. However,
      further activation with protein kinase C agonists was required for IL-2 activated
      CLL cells to stimulate autologous T cells sufficiently to clear bystander CLL
      cells from mixed lymphocyte responses. IL-15 had similar effects on the
      costimulatory properties of CLL cells. These results suggest a role for IL-2, or
      IL-15, in immunotherapeutic strategies for CLL.

PMID- 15566357
TI  - High-dose melphalan with autologous stem cell transplantation after VAD induction
      chemotherapy for treatment of amyloid light chain amyloidosis: a single centre
      prospective phase II study.
AB  - Amyloid light chain (AL) amyloidosis is the result of a clonal plasma cell
      expansion, in which monoclonal light chains transform to amyloid deposit in
      various tissues and can lead to organ dysfunction and organ failure. The median
      survival of patients with AL amyloidosis without therapy is 10-14 months. With
      high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT),
      haematological and clinical remission rates of up to 50% of treated patients have
      been reported from phase II studies. HDM followed by ASCT appears to prolong
      survival in patients, if haematological remission can be reached. In this phase
      II study, we evaluated vincristine, adriamycin and dexamethasone (VAD) as
      induction chemotherapy prior to stem cell mobilization and HDM with ASCT. The
      regimen was, in general, feasible in patients with AL amyloidosis, but VAD
      chemotherapy had a considerable World Health Organization (WHO) grade III-IV
      toxicity (25%) and mortality (7%) rate. VAD pretreatment did not interfere with
      stem cell mobilization and HDM with ASCT was possible in 86% of patients. The
      overall treatment efficacy was comparable with reported results of HDM and ASCT
      without preceding chemotherapy. We could not show an additional benefit of VAD
      induction in terms of increasing haematological response rate; however the 13%
      mortality rate after HDM and ASCT in our series was lower than the previous
      report.

PMID- 15566358
TI  - A novel method for simultaneous analysis of specific platelet antibodies: SASPA.
AB  - Glycoprotein (GP)-specific platelet antibodies can cause allo-immune and auto
      immune thrombocytopenia. The specific detection of relevant antibodies is a
      prerequisite for diagnosis and treatment. Here, we describe an improved method
      based on simultaneous detection of various platelet-specific immunoglobulin G
      (IgG) and IgM antibodies. Bead populations with distinct fluorescence
      intensities, coated with monoclonal antibodies specific for mouse heavy chain
      isotypes, were used for the simultaneous immobilization of platelet-GP [IIb/IIIa,
      Ib/IX, human leucocyte antigen (HLA) class I, or Ia/IIa, CD32, GPIV or CD109,
      Ib/IX, HLA class I]. In order to detect human IgG and IgM antibodies
      simultaneously, phycoerythrin- and fluorescein isotiocyanate-conjugated goat anti
      human IgG and IgM were added. On this basis, the abundance of six distinct
      antibodies (three anti-GP, each with subclasses IgG and IgM) were simultaneously
      analysed without cross-reaction by flow cytometry. For evaluation, sera and
      platelets from 169 patients with platelet-binding and/or platelet-associated
      antibodies were investigated. The monoclonal antibody-specific immobilization of
      platelet antigen (MAIPA) assay was performed in parallel as reference test. The
      simultaneous analysis of platelet-specific antibodies (SASPA) assay was able to
      detect all platelet-specific IgG and IgM that were also recognized by MAIPA with
      a comparable sensitivity. SASPA proved to be a rapid and reliable assay that
      required less platelets than other methods. This method has the potential to pave
      the way for new investigations of platelet-specific antibodies.

PMID- 15566359
TI  - Platelet count, previous infection and FCGR2B genotype predict development of
      chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood:
      results of a prospective study.
AB  - About 25-30% of children with acute idiopathic thrombocytopenia (ITP) develop
      chronic disease. It is not well known which patient characteristics influence the
      course of the ITP. A prospective study in 60 children with newly diagnosed ITP
      was performed. The aim of the study was to identify patient characteristics at
      the onset of thrombocytopenia that predicts the progression to chronic ITP.
      Clinical data and blood samples were collected at several time points during the
      first 6 months of the disease. Variables predicting chronic disease, as
      calculated in a multivariate logistic regression analysis, were a platelet count
      >10 x 10(9)/l at the onset [odds ratio (OR) 1.1, 95% confidence interval (CI)
      1.01-1.14], the absence of infection shortly before the onset of the disease (OR
      4.8, CI 1.16-19.57) and FGR2B-232I/T genotype (OR 7.9, CI 0.96-65.27). The latter
      may point at an immune-modulating role of Fc gamma RIIb in ITP. Although only
      three patients had serious bleeds, 35 patients received immune-modulating
      treatment for low platelet counts only. Seventeen patients were treated with
      intravenous immunoglobulin (IVIG) and 18 patients received corticosteroids.
      Patient variables did not differ between these treatment groups. However,
      patients receiving IVIG had significantly lower risk for chronic disease.

PMID- 15566360
TI  - Biosynthesis of FVIII in megakaryocytic cells: improved production and
      biochemical characterization.
AB  - Haemophilia A is an attractive target for gene therapy. We designed a haemophilia
      A gene therapy strategy involving the genetic modification of haematopoietic stem
      cells to achieve tissue-specific expression of a factor VIII (FVIII) transgene in
      the megakaryocytic lineage. Platelets would then serve as vehicles to store the
      expressed FVIII and deliver the coagulation factor at the site of vascular
      injury. A local correction of the haemostasis defect could, therefore, be
      expected following platelet activation and secretion. In this study, we
      demonstrated that a model of haematopoietic cell lines (Dami cells) could produce
      a correctly processed FVIII. FVIII transgenes were placed under the control of
      the human platelet glycoprotein IIb (GPIIb) promoter and used for stable
      transfection of the Dami megakaryocytic cell line. The highest FVIII production
      was obtained when the FVIII transgene contained a factor IX intron 1 gene
      sequence inserted in the FVIII intron 1 and 13 sites. Reverse transcription
      polymerase chain reaction demonstrated that the splicing of these introns was
      complete. Recombinant FVIII (rFVIII) produced in Dami cells was a biologically
      active molecule (specific activity: 5664 IU/mg) that was correctly glycosylated
      and sulphated. This recombinant FVIII protein exhibited biochemical
      characteristics after deglycosylation or thrombin activation that were comparable
      to a commercially available B-domainless rFVIII. These results demonstrate the
      advantages of a modified FVIII transgene and represent the first biochemical
      characterization of megakaryocyte-produced FVIII.

PMID- 15566361
TI  - The P303T mutation in the human factor VII (FVII) gene alters the conformational
      state of the enzyme and causes a severe functional deficiency.
AB  - We report the results of in vitro expression and biochemical characterization of
      the naturally occurring type II mutation Pro303Thr (P303T) in the factor VII
      (FVII) gene. Recombinant activated mutated FVII (FVIIa303T), compared with the
      activated wild-type FVII (FVIIaWT), showed reduced amidase activity toward
      synthetic substrates, especially when the observed reduced binding affinity for
      human soluble tissue factor (TF) (K(d) from 4.4 nmol/l for FVIIaWT to 17.3 nmol/l
      for FVIIa303T) was overcome by a fully saturating TF concentration. Likewise,
      factor X (FX) hydrolysis by FVIIa303T showed a reduced activity in the absence
      (and more severely in the presence) of TF (k(cat)/K(m) from 2.3 x 10(7)/mol/l s
      for FVIIaWT to 8.7 x 10(5)/mol/l s for FVIIa303T). These results showed that the
      mutant FVIIa is more shifted toward a zymogen-like form compared to FVIIaWT,
      suggesting that P303 facilitates the conformational transitions that stabilize
      the active form of FVIIa. The alteration of these allosteric equilibria is
      especially evident in the presence of TF, which was unable to shift the
      equilibrium toward a fully active FVIIa form. Additional experiments showed that
      both TF-catalysed FVII303T autoactivation and FVII303T activation by activated FX
      in the presence of TF were severely impaired, mainly because of an increase of
      the K(m) value. Altogether, these defects may explain the severe bleeding
      symptoms in a patient carrying the FVIIP303T mutation.

PMID- 15566362
TI  - Pathology of bone marrow in human herpes virus-8 (HHV8)-associated multicentric
      Castleman disease.
AB  - Human herpes virus-8 (HHV8)-associated multicentric Castleman disease (MCD) is an
      unusual systemic lymphoid hyperplasia induced by HHV8-infected B cells. Most
      cases develop in the background of human immunodeficiency virus (HIV) infection.
      Despite the haematological problems at presentation and the difficulties in the
      initial diagnosis, the bone marrow appearances of MCD have not been described. In
      this study we examined the pathology of bone marrow in MCD with a view to
      identify the features that may be helpful in early diagnosis. Bone marrow
      aspirates and biopsies from 13 cases of MCD (11 of which were HIV+) and 66
      control bone marrow biopsies from HIV-infected cases were studied. The specimens
      were routinely processed and stained. Immunohistochemistry for HHV8,
      immunoglobulin light chains, B-cell and plasma-cell markers was performed. The
      most important features were the presence of characteristic MCD lymphoid
      follicles containing HHV8+ plasmablasts in three of 13 cases of MCD and scattered
      interstitial HHV8+ plasmablasts in 11 of 13 cases. In control cases, no such
      follicles were seen and interstitial HHV8+ plasmablasts were rarely detected
      (four of 66 cases). Our results suggest that the presence of HHV8+ plasmablasts
      within lymphoid follicles and/or interstitium of the bone marrow are helpful
      features for the early diagnosis of MCD.

PMID- 15566363
TI  - Neutrophils secrete MIP-1 beta after adhesion to laminin contained in basement
      membrane of blood vessels.
AB  - We have recently demonstrated that granulocyte colony-stimulating factor (G-CSF)
      stimulated the production of epithelial-cell-derived-neutrophil attractant-78
      (ENA-78) by neutrophils and that ENA-78 might promote the accumulation of
      neutrophils that had migrated from the intravascular space into inflammatory
      tissues. In this study, we examined whether other chemokines could be secreted by
      neutrophils that had accumulated after migrating from the intravascular space
      into the inflammatory tissues. We demonstrated that adhesion to laminin contained
      in the basement membrane and Matrigel, which is an artificial basement membrane
      model, induced macrophage inflammatory protein-1 beta (MIP-1 beta) in neutrophils
      and that MIP-1 beta secreted by neutrophils induced the chemotaxis of dendritic
      cells. These findings suggest that neutrophils transmigrating through the
      basement membrane are stimulated to secrete MIP-1 beta by the basement membrane,
      inducing the transmigration of dendritic cells from the intravascular space into
      inflammatory tissues. We propose that neutrophils intervene between innate immune
      response and specific immune response by secreting MIP-1 beta during the
      transmigration through the basement membrane.

PMID- 15566364
TI  - Ferroportin gene silencing induces iron retention and enhances ferritin synthesis
      in human macrophages.
AB  - Missense mutations in the ferroportin gene (SLC11A3) result in haemochromatosis
      type 4 [HFE4, Online Mendelian Inheritance in Man (OMIM) reference 606069] or
      ferroportin disease, an autosomal dominant disorder characterized by
      predominantly reticuloendothelial iron accumulation. To verify whether HFE4 is
      caused by defective iron recycling because of loss of functionality of
      ferroportin, we down-regulated SLC11A gene expression in human macrophages by
      using small interfering RNAs (siRNAs). Transfection experiments with ferroportin
      siRNAs resulted in a marked reduction (about two-thirds on average) in
      ferroportin mRNA levels as detected by quantitative real time polymerase chain
      reaction. When macrophages were grown in medium supplemented with iron, cells
      transfected with siRNAs displayed three- to eightfold increases in staining
      intensities following Perls reaction. These macrophages also showed significant
      increases in H-ferritin content. The observation that ferroportin mRNA down
      regulation to levels compatible with haplo-insufficiency causes increased iron
      retention and H-ferritin synthesis in cultured macrophages has important
      implications. First, this indicates that ferroportin levels must be finely
      regulated in order to maintain cellular iron homeostasis, and that both copies of
      SLC11A3 must function efficiently to prevent iron accumulation. Second, this
      observation supports the hypothesis that reticuloendothelial iron overload in
      patients with ferroportin disease is caused by loss-of-function mutations in the
      SLC11A3 gene that mainly impair macrophage iron recycling.

PMID- 15566365
TI  - Somatic deletion of the normal beta-globin gene leading to thalassaemia
      intermedia in heterozygous beta-thalassaemic patients.
AB  - Two beta-thalassaemia patients, whose constitutive genotype was
      beta(39C)/beta(39C-->T), had the clinical phenotype beta-thalassaemia intermedia.
      Analysis of leucocyte DNA showed the presence of the mutated beta(39C-->T)-gene
      exclusively, while the normal beta(39C)-gene was also present in reticulocyte
      RNA. Deletional analysis of chromosome 11p15.5 on leucocyte DNA showed large
      deletions including the beta-globin gene. Two populations of erythroid
      progenitors, one heterozygous and the other hemizygous for the beta(39C-->T)
      mutation, were demonstrated in one case. This confirms that, in heterozygous
      individuals, beta-thalassaemia intermedia may be caused by inactivation of the
      beta-locus in trans as a result of chromosome 11p15.5 deletions in a
      subpopulation of haematopoietic cells.

PMID- 15566366
TI  - Rituximab in chronic, recurrent HIV-associated immune thrombocytopenic purpura.

PMID- 15566367
TI  - Implication of SOCS-1 gene methylation in acute myeloid leukaemia.

PMID- 15566368
TI  - How frequent is SOCS1 methylation in acute myeloid leukaemia?

PMID- 15566369
TI  - Maternal intrusiveness, maternal warmth, and mother-toddler relationship
      outcomes: variations across low-income ethnic and acculturation groups.
AB  - The present study investigated the extent to which maternal intrusiveness and
      warmth during play, observed in 579 European American, 412 African American, and
      110 more and 131 less acculturated Mexican American low-income families when
      children were approximately 15 months old, predicted 3 dimensions of the mother
      toddler relationship 10 months later. Intrusiveness predicted increases in later
      child negativity in all 4 groups. Among African Americans only, this association
      was moderated by maternal warmth. Intrusiveness predicted negative change in
      child engagement with mothers only in European American families. Finally, near
      significant trends suggested that intrusiveness predicted later decreased dyadic
      mutuality in European American and more acculturated Mexican American families,
      but not in African American or less acculturated Mexican American families.

PMID- 15566370
TI  - Economic stress, parenting, and child adjustment in Mexican American and European
      American families.
AB  - To assess the impact of economic hardship on 111 European American and 167
      Mexican American families and their 5th-grade (M age=11.4 years) children, a
      family stress model was evaluated. Structural equation analyses revealed that
      economic hardship was linked to indexes of economic pressure that were related to
      depressive symptoms for mothers and fathers of both ethnicities. Depressive
      symptoms were linked to marital problems and hostile parenting. Paternal hostile
      parenting was related to child adjustment problems for European Americans,
      whereas marital problems were linked to child adjustment problems for Mexican
      Americans. Maternal acculturation was associated with both higher marital
      problems and lower hostile parenting. The utility of the model for describing the
      effects of economic hardship in Mexican Americans is noted.

PMID- 15566371
TI  - Development of mutual responsiveness between parents and their young children.
AB  - This comprehensive study of mutual responsiveness examined 102 mothers and 102
      fathers interacting with their children at 7 and 15 months. Responsiveness was
      studied from developmental and individual differences perspectives, and assessed
      using macroscopic ratings and microscopic event coding. The latter captured
      parents' reactions to children's negative, positive, and physical bids, and
      children's reactions to parents' social-interactive bids, mood regulation
      attempts, and influence attempts. Responsiveness depended on bid type and child
      age, and reflected developmental changes in children, parents, and relationships.
      Mothers were more responsive than fathers; children were equally responsive to
      both parents and coherent in their responsiveness. Ratings revealed dyadic
      mutuality and longitudinal continuity of responsiveness. Parent-child
      responsiveness from 7 to 15 months was consistent with assumptions of a parent
      driven process.

PMID- 15566372
TI  - Attachment and attention: protection in relation to gender and cumulative social
      contextual adversity.
AB  - Data from 918 children from the National Institute of Child Health and Human
      Development (NICHD) Study of Early Child Care were examined to test the
      interrelation of attachment and attentional performance and 2 known risks for
      poor attentional performance: male gender and social-contextual adversity.
      Attachment was measured using the Strange Situation at 15 months, attentional
      performance by a Continuous Performance Test (CPT) and maternal questionnaires at
      54 months, and social-contextual adversity by a variety of measures from birth to
      54 months. Findings indicated (a) that children with secure attachment were less
      susceptible to the effects of cumulative risk and gender on CPT attentional
      performance than their insecure counterparts and that (b) no such differential
      risk susceptibility was evident for maternal reports of attention-related
      behavior problems.

PMID- 15566373
TI  - Children's developing awareness of diversity in people's trains of thought.
AB  - This research explored the development of one insight about the mind, namely, the
      belief that people's trains of thought differ even when they see the same
      stimulus. In Study 1, 5-year-olds, 9-year-olds, and adults heard stories about
      characters who saw the same object. Although the older groups predicted the
      object would trigger different trains of thought, most 5-year-olds did not. In
      Study 2, 5-year-olds (preschoolers and kindergartners) and 7-year-olds heard
      similar stories, plus stories with additional individuating information about
      each character. With age, children increasingly recognized that thoughts would
      differ and could explain why. The development of this insight during the school
      years likely provides children with a more complete understanding of what it
      means to be a unique individual.

PMID- 15566374
TI  - Transfer by very young children in the symbolic retrieval task.
AB  - Cumulative experience with a variety of symbolic artifacts has been hypothesized
      as a source of young children's increasing sensitivity to new symbol-referent
      relations. Evidence for this hypothesis comes from transfer studies showing that
      experience with a relatively easy symbolic retrieval task improves performance on
      a more difficult task. Significant transfer was found for the 2(1/2)-year-old
      children in the 3 studies reported here, even with relatively low levels of
      contextual support (according to the taxonomy of transfer by Barnett & Ceci,
      2002). Transfer occurred even though the 2 tasks were encountered in very
      different settings and there was a prolonged (1-week) delay interval between
      them. Transfer also occurred to a much more difficult task (one that even 3-year
      olds typically fail).

PMID- 15566375
TI  - Category-use effects in children.
AB  - Three experiments examined the changes in category representation that take place
      when children use exemplars for tasks other than classification. In Experiments 1
      and 2, 6- and 10-year-old children learned to classify exemplars of a novel
      category and then used the same exemplars in an inferential prediction task. In a
      subsequent classification task, features that were predictive for both
      classification and inference were classified more accurately than features that
      were predictive only of category membership. Experiment 3 showed that features
      with multiple uses were also more likely to be retrieved in feature listing. The
      findings show that children's category representations are affected by the way
      exemplars are used after they have been categorized.

PMID- 15566376
TI  - Modeling referential actions in 6- to 18-month-old infants: a precursor to
      symbolic understanding.
AB  - Social precursors to symbolic understanding of pictures were examined with 100
      infants ages 6, 9, 12, 15, and 18 months. Adults demonstrated 1 of 2 stances
      toward pictures and objects (contemplative or manipulative), and then gave items
      to infants for exploration. For pictures, older infants (12, 15, and 18 months)
      emulated the adult's actions following both types of demonstration trials. For
      objects, infants did not emulate actions following either stance at any age. The
      findings suggest that infants enlist their imitative learning skills in the
      context of learning the conventions of action on pictorial symbols. The data are
      interpreted as pointing to the importance of social learning in developing an
      understanding of the referential function of pictorial symbols.

PMID- 15566377
TI  - Developmental consequences of early parenting experiences: self-recognition and
      self-regulation in three cultural communities.
AB  - This study relates parenting of 3-month-old children to children's self
      recognition and self-regulation at 18 to 20 months. As hypothesized,
      observational data revealed differences in the sociocultural orientations of the
      3 cultural samples' parenting styles and in toddlers' development of self
      recognition and self-regulation. Children of Cameroonian Nso farmers who
      experience a proximal parenting style develop self-regulation earlier, children
      of Greek urban middle-class families who experience a distal parenting style
      develop self-recognition earlier, and children of Costa Rican middle-class
      families who experience aspects of both distal and proximal parenting styles fall
      between the other 2 groups on both self-regulation and self-recognition. Results
      are discussed with respect to their implications for culturally informed
      developmental pathways.

PMID- 15566378
TI  - Comparison of sadness, anger, and fear facial expressions when toddlers look at
      their mothers.
AB  - Research suggests that sadness expressions may be more beneficial to children
      than other emotions when eliciting support from caregivers. It is unclear,
      however, when children develop the ability to regulate their displays of
      distress. The current study addressed this question. Distress facial expressions
      (e.g., fear, anger, and sadness) were examined in 24-month-old toddlers
      throughout 4 episodes as well as specifically during looks to their mothers.
      Consistent with hypotheses and the literature, toddlers expressed sadness more
      frequently and with more intensity than target emotions only during looks to
      their mothers. These findings indicate that toddlers as young as 24 months of age
      are using particular emotional displays to elicit support from the social
      environment.

PMID- 15566379
TI  - Parenting stress, infant emotion regulation, maternal sensitivity, and the
      cognitive development of triplets: a model for parent and child influences in a
      unique ecology.
AB  - To examine the development of triplets, 23 sets of triplets were matched with 23
      sets of twins and 23 singletons (N=138). Maternal sensitivity was observed at
      newborn, 3, 6, and 12 months, and infants' cognitive and symbolic skills at 1
      year. Triplets received lower maternal sensitivity across infancy and exhibited
      poorer cognitive competencies compared with singletons and twins. The most
      medically compromised triplet showed the lowest regulation, received lower
      maternal sensitivity, and demonstrated the weakest outcomes compared with
      siblings. Structural modeling charted three levels of influence on cognitive
      outcomes: direct, indirect, and contextual. The triplet ecology provides a
      context for assessing the relations among infant inborn dispositions, the rearing
      environment, and the role of exclusive parenting in development.

PMID- 15566380
TI  - Stability and change in attachment security across adolescence.
AB  - This study examined both continuity and familial, intrapsychic, and environmental
      predictors of change in adolescent attachment security across a 2-year period
      from middle to late adolescence. Assessments included the Adult Attachment
      Interview, observed mother-adolescent interactions, test-based data, and
      adolescent self-reports obtained from an ethnically and socioeconomically diverse
      sample of moderately at-risk adolescents interviewed at ages 16 and 18.
      Substantial stability in security was identified. Beyond this stability, however,
      relative declines in attachment security were predicted by adolescents' enmeshed,
      overpersonalizing behavior with their mothers; depressive symptoms; and poverty
      status. Results suggest that although security may trend upward for nonstressed
      adolescents, stressors that overwhelm the capacity for affect regulation and that
      are not easily assuaged by parents predict relative declines in security over
      time.

PMID- 15566381
TI  - Fathers and mothers at play with their 2- and 3-year-olds: contributions to
      language and cognitive development.
AB  - Father-child and mother-child engagements were examined longitudinally in
      relation to children's language and cognitive development at 24 and 36 months.
      The study involved a racially/ethnically diverse sample of low-income, resident
      fathers (and their partners) from the National Early Head Start evaluation study
      (n=290). Father-child and mother-child engagements were videotaped for 10 min at
      home during semistructured free play, and children's language and cognitive
      status were assessed at both ages. Fathers' and mothers' supportive parenting
      independently predicted children's outcomes after covarying significant
      demographic factors. Moreover, fathers' education and income were uniquely
      associated with child measures, and fathers' education consistently predicted the
      quality of mother-child engagements. Findings suggest direct and indirect effects
      of fathering on child development.

PMID- 15566382
TI  - Development of self-recognition, personal pronoun use, and pretend play during
      the 2nd year.
AB  - This study examined the relation of visual self-recognition to personal pronoun
      use and pretend play. For a longitudinal sample (N=66) at the ages when self
      recognition was emerging (15, 18, and 21 months), self-recognition was related to
      personal pronoun use and pretend play such that children showing self-recognition
      used more personal pronouns and demonstrated more advanced pretend play than did
      children not showing self-recognition. The finding of a relation among these
      measures provides additional evidence that in the middle of the 2nd year of life
      a metarepresentation of self emerges in the human child.

PMID- 15566383
TI  - Cumulative environmental risk and youth maladjustment: the role of youth
      attributes.
AB  - Using data from 5,070 youth ages 11 to 18 years old who participated in the
      National Longitudinal Study of Adolescent Health, concurrent and longitudinal
      associations among cumulative risk, protective factors, and youth maladjustment
      were examined. Cumulative risk was associated with concurrent conduct problems
      and depressed mood. For conduct problems, a compensatory effect was found for
      scholastic achievement and problem-solving ability. For depressed mood, a
      compensatory effect was found for scholastic achievement. A protective-reactive
      effect of self-esteem was found for both forms of maladjustment. Youth gender,
      grade, and ethnicity moderated these associations. Cumulative risk predicted
      change over time in depressed mood. Scholastic achievement and self-esteem
      compensated for this risk. Findings indicate that youth attributes offer limited
      protection when adolescents experience risk factors across life domains.

PMID- 15566384
TI  - Is a picture worth a thousand words? The flexible nature of modality dominance in
      young children.
AB  - When presented simultaneously with equally discriminable, but unfamiliar, visual
      and auditory stimuli, 4-year-olds exhibited auditory dominance, processing only
      auditory information (Sloutsky & Napolitano, 2003). The current study examined
      factors underlying auditory dominance. In 6 experiments, 4-year-olds (N=181) were
      presented with auditory and visual compounds in which (a) the complexity and
      familiarity of stimuli were systematically varied (Experiments 1-5) and (b)
      participants were explicitly instructed to attend to a particular modality
      (Experiment 6). Results indicate that auditory dominance is a special case of
      flexible modality dominance, which may stem from automatic pulls on attention.
      Theoretical implications of these results for understanding the development of
      attention and cross-modal processing, as well as linguistic and conceptual
      development, are discussed.

PMID- 15566385
TI  - Don't believe everything you hear: preschoolers' sensitivity to speaker intent in
      category induction.
AB  - A label can convey nonobvious information about category membership. Three
      studies show that preschoolers (N=144) sometimes ignore or reject labels that
      conflict with appearance, particularly when they are uncertain that the speaker
      meant to use those labels. In Study 1, 4-year-olds were more reluctant than 3
      year-olds to accept that, for example, a cat-like animal was a dog just on the
      basis of hearing it called a dog. In Studies 2 and 3, this reluctance was
      overcome when the speaker explicitly or implicitly indicated that use of the
      unexpected labels was intentional. These studies demonstrate that preschoolers do
      not treat labels as atheoretical features of objects; rather, they interpret them
      in light of their understanding of the labeler's communicative intent.

PMID- 15566386
TI  - Psychosocial adjustment, school outcomes, and romantic relationships of
      adolescents with same-sex parents.
AB  - This study examined associations among family type (same-sex vs. opposite-sex
      parents); family and relationship variables; and the psychosocial adjustment,
      school outcomes, and romantic attractions and behaviors of adolescents.
      Participants included 44 12- to 18-year-old adolescents parented by same-sex
      couples and 44 same-aged adolescents parented by opposite-sex couples, matched on
      demographic characteristics and drawn from a national sample. Normative analyses
      indicated that, on measures of psychosocial adjustment and school outcomes,
      adolescents were functioning well, and their adjustment was not generally
      associated with family type. Assessments of romantic relationships and sexual
      behavior were not associated with family type. Regardless of family type,
      adolescents whose parents described closer relationships with them reported
      better school adjustment.

PMID- 15566388
TI  - Multiple levels of sensory integration in the intrinsic sensory neurons of the
      enteric nervous system.
AB  - 1. The enteric nervous system (ENS) is present in the wall of the
      gastrointestinal tract and contains all the functional classes of neuron required
      for complete reflex arcs. One of the most important and intriguing classes of
      neuron is that responsive to sensory stimuli: sensory neurons with cell bodies
      intrinsic to the ENS. 2. These neurons have three outstanding and interrelated
      features: (i) reciprocal connections with each other; (ii) a slow excitatory post
      synaptic potential (EPSP) resulting from high-speed firing in other sensory
      neurons; and (iii) a large after-hyperpolarizing potential (AHP) at the soma.
      Slow EPSP depolarize the cell body, generate action potentials (APs) and reduce
      the AHP. Conversely, the AHP limits the firing rate and, hence, reduces
      transmission of slow EPSP. 3. Processing of sensory information starts at the
      input terminals as different patterns of APs depending on the sensory modality
      and recent sensory history. At the soma, the ability to fire APs and, hence,
      drive outputs is also strongly determined by the recent firing history of the
      neuron (through the AHP) and network activity (through the slow EPSP). Positive
      feedback within the population of intrinsic sensory neurons means that the
      network is able to drive outputs well beyond the duration of the stimuli that
      triggered them. 4. Thus, sensory input and subsequent reflex generation are
      integrated over several hierarchical levels within the network on intrinsic
      sensory neurons.

PMID- 15566389
TI  - Captopril reverses the reduced vasodilator response to bradykinin in hypertensive
      pregnant rats.
AB  - 1. Pregnancy in rats is characterized by a reduction in arterial pressure that is
      associated with a decreased response to vasoconstrictors. However, the responses
      to vasodilators in isolated vessels remain controversial and are not well
      established in hypertensive pregnant rats. 2. In the present study, we
      investigated the effect of pregnancy on the bradykinin (BK)-induced vasodilator
      responses of the isolated mesenteric arterial bed (MAB) from Wistar normotensive
      and spontaneously hypertensive rats (SHR) and determined the role of nitric oxide
      (NO), endothelium-derived hyperpolarizing factor (EDHF) and angiotensin
      converting enzyme (ACE) in these responses. 3. Mean arterial pressure (MAP) in
      pregnant normotensive and pregnant hypertensive rats (93 +/- 1 and 122 +/- 2
      mmHg, respectively) was lower than in non-pregnant controls (128 +/- 1 and 163 +/
      2 mmHg, respectively; P < 0.05). In MAB isolated from normotensive rats and
      precontracted with phenylephrine, the effects of bradykinin, acetylcholine (ACh)
      and nitroglycerine (NG) were not influenced by pregnancy. In contrast, the
      vasodilator responses to BK were significantly reduced in pregnant compared with
      non-pregnant SHR and seemed to be specific to BK. 4. The ACE inhibitor captopril
      potentiated BK vasodilator responses and abolished the differences between
      pregnant and non-pregnant SHR. Inhibition of nitric oxide (NO) synthase by N(G)
      nitro-L-arginine methyl ester (l-NAME) significantly reduced the vasodilator
      effect of BK in all groups. In the presence of l-NAME plus high K+ solution (47
      mmol/L), BK-induced vasodilation was completely blocked. The NO-dependent
      component of the responses seems to be more important in hypertensive rats and
      pregnancy does not modify this profile. 5. Our results suggest that increased ACE
      activity may be involved in the pregnancy associated reduction in vasodilator
      responses to BK in the MAB of hypertensive rats. Pregnancy does not modify the
      relative contribution of the EDHF and NO to the vasodilator effect of BK.

PMID- 15566390
TI  - Effects of glutamate transport substrates and glutamate receptor ligands on the
      activity of Na-/K(+)-ATPase in brain tissue in vitro.
AB  - 1. It has been suggested that Na+/K(+)-ATPase and Na(+)-dependent glutamate
      transport (GluT) are tightly linked in brain tissue. In the present study, we
      have investigated Na+/K(+)-ATPase activity using Rb+ uptake by 'minislices'
      (prisms) of the cerebral cortex. This preparation preserves the morphology of
      neurons, synapses and astrocytes and is known to possess potent GluT that has
      been well characterized. Uptake of Rb+ was determined by estimating Rb+ in
      aqueous extracts of the minislices, using atomic absorption spectroscopy. 2. We
      determined the potencies of several known substrates/inhibitors of GluT, such as
      L-trans-pyrrolidine-2,4-dicarboxylate (LtPDC), DL-threo-3-benzyloxyaspartic acid,
      (2S,3S,4R)-2-(carboxycyclopropyl)-glycine (L-CCG III) and L-anti,endo-3,4
      methanopyrrolidine dicarboxylic acid, as inhibitors of [3H]-L-glutamate uptake by
      cortical prisms. In addition, we established the susceptibility of GluT, measured
      as [3H]-L-glutamate uptake in brain cortical prisms, to the inhibition of
      Na+/K(+)-ATPase by ouabain. Then, we tested the hypothesis that the Na+/K(+)
      ATPase (measured as Rb+ uptake) can respond to changes in the activity of GluT
      produced by using GluT substrates as GluT-specific pharmacological tools. 3. The
      Na+/K(+)-ATPase inhibitor ouabain completely blocked Rb+ uptake (IC50 = 17
      micromol/L), but it also potently inhibited a fraction of GluT (approximately 50%
      of [3H]-L-glutamate uptake was eliminated; IC50 < 1 micromol/L). 4. None of the
      most commonly used GluT substrates and inhibitors, such as L-aspartate, D
      aspartate, L-CCG III and LtPDC (all at 500 micromol/L), produced any significant
      changes in Rb+ uptake. 5. The N-methyl-D-aspartate (NMDA) receptor agonists (R,S)
      (tetrazol-5-yl)-glycine and NMDA decreased Rb+ uptake in a manner compatible with
      their known neurotoxic actions. 6. None of the agonists or antagonists for any of
      the other major classes of glutamate receptors caused significant changes in Rb+
      uptake. 7. We conclude that, even if a subpopulation of glutamate transporters in
      the rat cerebral cortex may be intimately linked to a fraction of Na+/K(+)
      ATPase, it is not possible, under the present experimental conditions, to detect
      regulation of Na+/K(+)-ATPase by GluT.

PMID- 15566391
TI  - Effects of vitamin E on the cinnamaldehyde-induced apoptotic mechanism in human
      PLC/PRF/5 cells.
AB  - 1. Cinnamaldehyde has been shown to be effective in inducing cell apoptosis in a
      number of human cancer cells. The aim of the present study was to investigate the
      effect of vitamin E on the apoptotic signalling mechanism induced by
      cinnamaldehyde in human hepatoma PLC/PRF/5 cells. 2. Using the XTT assay,
      cinnamaldehyde exhibited a powerful antiproliferative effect on PLC/PRF/5 cells.
      Apoptosis was elicited when cells were treated with 1 micromol/L cinnamaldehyde,
      as characterized by the appearance of phosphatidylserine on the outer surface of
      the plasma membrane. 3. The apoptotic effect induced by cinnamaldehyde could be
      further supported by the release of cytochrome c, Smac/Diablo and Omi/HtrA2 from
      mitochondria to the cytosol and activation of caspase 3. Cinnamaldehyde also
      upregulated the expression of pro-apoptotic protein (Bax) and down-regulated the
      levels of anti-apoptotic proteins, such as Bcl-2 and the inhibitor of apoptosis
      protein family (X-linked inhibitor of apoptosis protein (XIAP), cellular
      inhibitor of apoptosis protein (cIAP)-1 and cIAP-2). 4. Cinnamaldehyde induces
      the generation of reactive oxygen species (ROS) in cells. Following the pre
      incubation of PLC/PRF/5 cells with anti-oxidants, it was found that 100
      micromol/L vitamin E significantly diminished the effect of cinnamaldehyde
      induced apoptosis, whereas a lesser effect was seen with on 100 micromol/L N
      acetyl-L-cysteine. Vitamin E effectively blocked the release of cytochrome c,
      Smac/Diablo and Omi/HtrA2 from mitochondria to the cytosol in cells treated with
      cinnamaldehyde. Vitamin E also markedly suppressed caspase 3 activation. The
      expression of apoptotic inhibitors (XIAP, cIAP-1, cIAP-2) and anti-apoptotic (Bcl
      2) and pro-apoptotic (Bax) proteins was affected by vitamin E pretreatment. 5.
      Taken together, the results suggest that cinnamaldehyde triggers apoptosis
      possibly through the mitochondrial pathway. Pretreatment with vitamin E markedly
      prevented cinnamaldehyde-mediated apoptosis, which was associated with the
      modulation of XIAP, cIAP-1, cIAP-2, Bcl-2 and Bax protein activity.

PMID- 15566392
TI  - Randomized trial of a single, double and triple dose of 10 mg/kg of a human
      formulation of triclabendazole in patients with fascioliasis.
AB  - 1. A study performed > 10 years ago and case reports published recently suggest
      that triclabendazole is effective for the treatment of patients with
      fascioliasis. 2. To confirm the efficacy of a human formulation of
      triclabendazole, we enrolled 165 patients into the present study and divided the
      subjects into two groups: (i) those who had fascioliasis, as evidenced by the
      presence of ova in their stools; and (ii) patients with clinical and laboratory
      data suggesting fascioliasis. 3. Patients were randomly allocated to receive 10
      mg/kg, p.o., triclabendazole for 1, 2 or 3 days (single-, double- and triple-dose
      groups, respectively). Medical history and physical and laboratory examinations
      were performed at baseline and at 7, 14, 30 and 60 days after treatment. Results
      were based on 152 patients who completed the study. 4. A sharp decrease in the
      proportion of clinical signs and symptoms was observed in all groups immediately
      after treatment. Ova disappeared from the stools of all patients in the single-
      and double-dose groups. Thirty days after treatment, ova were identified in the
      stools of two patients in the triple-dose group who received a second course of
      triclabendazole. 5. All cases were cured on day 60. However, the cure rate was
      lower when the patients with suggestive fascioliasis were included in the
      analysis. The cure rate was not significantly different (P > 0.05) among the
      three dose groups. No cases of toxic hepatitis were observed. 6. In conclusion,
      oral administration of 10 mg/kg of the human pharmaceutical preparation of
      triclabendazole for 1-3 days is safe and effective in the treatment of human
      fascioliasis.

PMID- 15566393
TI  - Circadian changes in the QT variability index in the beagle dog.
AB  - 1. QT variability is a non-invasive marker of cardiac repolarization lability and
      a higher QT variability is associated with sudden death. No data exist as to the
      circadian fluctuations in QT variability and the QT variability index (QTvi) in
      the canine. The purpose of the present investigation was to explore QT interval
      variability over 24 h in the healthy dog. 2. Continuous lead II electrocardiogram
      and blood pressure data were collected for 24 h from three beagles instrumented
      with radiotelemetry devices. The mean heart rate (HR), detrended HR variance,
      mean QT interval and detrended QT variance were calculated from the instantaneous
      HR and QT time series of 1024 points (256 s), as described previously, and a
      normalized QTvi was derived. 3. The dog has a diurnal pattern of QTvi similar to
      healthy humans. Both dogs and humans exhibit a significantly higher QTvi during
      active waking hours, with more negative values during deep sleep. 4. These
      findings suggest QTvi may serve as an additional non-invasive tool to assess
      ventricular repolarization lability in dogs in relation to any conditions or
      drugs that are known to be associated with increased cardiac mortality.

PMID- 15566394
TI  - Vascular and anti-oxidant actions of flavonols and flavones.
AB  - 1. Flavonols and flavones are plant-derived polyphenolic compounds that are
      commonly consumed in the diet. Epidemiological studies indicating that high
      dietary intake of flavonols reduces the risk of mortality due to coronary heart
      disease have provoked interest in the mechanism of this cardioprotective effect.
      2. We have investigated the structure-activity relationships of a range of
      flavonols and flavones with regard to their vascular relaxant and anti-oxidant
      activity. In rat isolated thoracic aorta, the synthetic flavonol 3',4'
      dihydroxyflavonol (DiOHF) was found to be a significantly more potent
      vasorelaxant than the naturally occurring compounds chrysin, apigenin, luteolin,
      quercetin and fisetin. Similarly, DiOHF was significantly more potent than those
      compounds in the inhibition of calcium-induced contraction of the rat aorta. 3.
      3',4'-Dihydroxyflavonol was also found to significantly inhibit superoxide
      radical generation in a cell-free system in the presence of xanthine/xanthine
      oxidase or by rat isolated aorta in the presence of NADPH. In the presence of
      oxidant stress generated by pyrogallol or xanthine/xanthine oxidase, endothelium
      dependent relaxation of rat aortic rings was impaired. 3',4'-Dihydroxyflavonol
      was able to significantly improve endothelium-dependent relaxation in the
      presence of those oxygen radical generators. 4. In addition, DiOHF was found to
      significantly improve dilatation in the rat hindquarters vasculature after
      exposure to ischaemia and reperfusion. 3',4'-Dihydroxyflavonol was found to be
      equally effective whether applied before ischaemia or during ischaemia just
      before reperfusion. 5. In conclusion, DiOHF is an effective vasodilator and anti
      oxidant that is able to prevent vascular reperfusion injury. We suggest that
      DiOHF may be useful as an adjunct to thrombolytic therapy in the management of
      reperfusion injury.

PMID- 15566395
TI  - Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic
      peptide: a brief review.
AB  - 1. If one was to design a hormone to protect the heart, it would have a number of
      features shown by the cardiac natriuretic peptides atrial natriuretic peptide
      (ANP) and B-type natriuretic peptide (BNP). These hormones are made in
      cardiomyocytes and are released into the circulation in response to atrial and
      ventricular stretch, respectively. Atrial natriuretic peptide and BNP can reduce
      the preload and after-load in normal and failing hearts. They reduce blood volume
      over the short term by sequestering plasma and over the longer term by promoting
      renal salt and water excretion and by antagonizing the renin-angiotensin
      aldosterone system at many levels. Each of these actions affords indirect benefit
      to a volume- or pressure-threatened heart. 2. Recent studies have identified
      additional modes of action of the natriuretic peptides that may also confer
      cardioprotective benefits, especially in heart disease. The emerging findings
      are: (i) that ANP and BNP antagonize the cardiac hypertrophic action of
      angiotensin II and continue working under conditions where endothelial nitric
      oxide (NO) function is compromised, such as in the presence of high glucose in
      diabetes; (ii) they potentiate the bradycardia caused by inhibitory
      ('autoprotective') cardio-cardiac reflexes; and, furthermore, (iii) BNP can
      suppress cardiac sympathetic nerve activity in humans, including those with heart
      failure. Thus, it appears that natriuretic peptides can shift sympathovagal
      balance in a beneficial direction (away from the sympathetic). The vagal reflex
      and antihypertrophic actions of the peptides are mediated by particulate guanylyl
      cyclase (pGC) natriuretic peptide receptors. 3. The multiple synergistic actions
      of the natriuretic peptides make them and their pGC receptors attractive targets
      for therapy in heart disease. Encouragingly, exogenous natriuretic peptides
      remain effective even when endogenous peptide levels are raised, as is the case
      in heart failure. They also remain effective in disease states where other
      protective mechanisms, such as the NO system, have become ineffective, offering
      yet further encouragement for the therapeutic use of the natriuretic peptides.

PMID- 15566396
TI  - Arterial stiffness, endothelial function and novel pharmacological approaches.
AB  - 1. Despite over half a century of intensive research, cardiovascular disease
      remains the leading cause of death world wide. Nevertheless, a number of risk
      factors for cardiovascular disease have been identified, such as hypertension and
      serum cholesterol, and therapies targeting such factors are effective in reducing
      cardiovascular and total mortality. Arterial stiffness is an additional
      independent risk factor for cardiovascular disease and strategies aimed at
      lowering arterial stiffness may be effective in reducing cardiovascular risk.
      However, in order to exploit fully the therapeutic potential of this approach, it
      is necessary first to understand the physiological and pathophysiological factors
      regulating the stiffness of the large arteries. 2. Until recently, stiffness was
      thought to depend largely upon structural components within the arterial wall,
      such as elastin and collagen and the distending pressure. However, we now
      recognize that arterial smooth muscle also regulates vessel stiffness and that a
      number of locally derived and circulating factors, including nitric oxide (NO),
      endothelin-1 and the natriuretic peptides, contribute to the short-term or
      functional regulation of large artery stiffness. Changes in the balance between
      these factors and, in particular, a reduction in NO production may well explain
      why conditions such as hypercholesterolaemia and diabetes are themselves
      associated with arterial stiffening before the development of manifest
      atherosclerosis. 3. The importance of smooth muscle in regulating arterial
      stiffness suggests that direct pharmacological manipulation of stiffness may be
      possible, thus providing novel therapeutic strategies to reduce cardiovascular
      risk. Furthermore, differences in the effect of existing drugs on larger artery
      stiffness may explain, in part, why some drugs produce better clinical outcomes
      than others.

PMID- 15566397
TI  - GABAC receptor ion channels.
AB  - 1. The present review gives an overview of studies conducted on GABAC receptors
      over the past 10 years since the author started at the University of Sydney. It
      concentrates on the structure-activity relationship profiles of the receptor and
      how these studies were used to: (i) develop selective GABAC receptor ligands; and
      (ii) understand the impact of amino acid changes on GABAC receptor pharmacology
      and function. 2. Structure-activity relationship studies involving variations of
      both ligands and their receptor targets are vital to the discovery of drugs that
      interact selectively with particular native and mutant receptor subtypes. Such
      agents may be useful for treating anxiety, depression, epilepsy and memory
      related disorders, such as Alzheimer's disease.

PMID- 15566398
TI  - Can we differentiate between airway and vascular smooth muscle?
AB  - 1. Airway smooth muscle (ASM) has recently been termed the 'frustrated' cell of
      the lung given that contraction of ASM has no proven useful physiological
      function in adults and yet is indelibly associated with pathological conditions
      by virtue of its unwanted airflow-limiting actions in asthma. In contrast,
      pulmonary vascular smooth muscle contraction plays an essential role in the
      control of blood flow through the lung. 2. Little is known of the differences in
      phenotype between human ASM and pulmonary vascular smooth muscle (VSM) tissues,
      but differences in contractile protein and transcription factor expression and
      regulation of contractile protein promoter activity have been documented.
      Similarly, the embryological signals in mice required for differentiation of ASM
      versus pulmonary VSM are distinct. 3. Bronchoconstriction in asthma is currently
      treated with beta2-adrenoceptor agonists, which relax contracted ASM cells. An
      additional approach may be to use gene therapy to render ASM unable to contract
      (via disruption of their contractile apparatus organization). 4. Application of
      ASM-specific gene therapies would rely on minimal actions on other lung smooth
      muscle tissues, including pulmonary and bronchial vascular smooth muscle. The
      combination of mRNA analysis of laser-captured microdissected tissue with in situ
      immunohistochemical staining for protein should be very useful in terms of being
      able to characterize definitively the differences in mRNA and protein expression
      between the smooth muscle species of the lung. Any discovery of an ASM-selective
      target could provide a novel lead for ASM-directed anti-asthma therapy.

PMID- 15566399
TI  - Nitroreductase: a prodrug-activating enzyme for cancer gene therapy.
AB  - 1. The prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) is activated by
      Escherichia coli nitroreductase (NTR) to a potent DNA-crosslinking agent. 2.
      Virus-mediated expression of NTR in tumour cells sensitizes them to CB1954 in
      vitro and in vivo, providing the basis for a strategy of cancer gene therapy. 3.
      A phase I trial of CB1954 in cancer patients has been completed, documenting the
      pharmacokinetics and establishing an acceptable dose. Subsequent trials of the
      replication-defective adenovirus CTL102 in patients with resectable tumours have
      documented expression of NTR in injected colorectal liver metastases,
      hepatocellular carcinoma, head and neck cancer and prostate cancer. Trials
      combining CTL102 and CB1954 are underway. 4. An oncolytic (replication-competent)
      adenovirus vector allowed increased expression of NTR in vitro and in a mouse
      tumour model, resulting in a greater reduction in tumour growth when combined
      with CB1954 treatment. 5. Alternative prodrugs may eventually prove superior to
      CB1954; a nitroaryl phosphoramide mustard prodrug activated by NTR shows a
      greater therapeutic index than CB1954 in a human ovarian carcinoma. 6. The
      crystal structure of NTR provided the basis for site-directed mutagenesis, which
      has identified a number of mutants with improved kinetics of CB1954 activation.
      These can provide improved cell sensitization to CB1954. Combinations of these
      are being tested. 7. The basis for a positive selection for improved NTR variants
      has been demonstrated.

PMID- 15566400
TI  - Enzymatic bioremediation: from enzyme discovery to applications.
AB  - 1. Enzymatic bioremediation is potentially a rapid method of removing
      environmental pesticide residues. Applications include the treatment of residues
      resulting from agricultural production and processing industries, such as the
      treatment of irrigation waters, surface-contaminated fruit and vegetables and
      spent dip liquors. 2. A specific application for some organophosphate-degrading
      enzymes involves detoxification of nerve agent stockpiles. Effective and
      affordable remediation requires highly specialized enzymes, so protein
      engineering techniques are being used to improve properties of various source
      enzymes to enhance catalytic rates, stability and substrate range. 3. Trials with
      an optimized organophosphate-degrading enzyme have shown the feasibility of such
      technology in various applications. 4. The enzymes developed for environmental
      remediation for specific pesticide classes also have applications as antidotes
      for high-dose pesticide poisonings and as prophylaxis for people at risk of high
      pesticide doses.

PMID- 15566401
TI  - The Janus faces of adrenoceptors: factors controlling the coupling of
      adrenoceptors to multiple signal transduction pathways.
AB  - 1. The adrenoceptors (AR) are an important subfamily of rhodopsin-like G-protein
      coupled receptors that couple to an increasingly large number of signalling
      mechanisms. Two important factors that determine the pathways that are used are
      the C-terminal region of the receptor and the agonist used to activate the
      receptor. 2. Studies of splice variants of the mouse beta3-AR showed that the C
      terminus is a factor controlling the signalling characteristics. Although these
      receptors differ only at the C-terminus, the beta3b-AR coupled to both Gs and Gi,
      whereas the beta3a-AR coupled solely to Gs. 3. Examination of four splice
      variants of the human alpha1A-AR showed that all were able to couple to pertussis
      toxin-sensitive G-proteins, even though they have radically different C-terminal
      regions. 4. Comparison of the effects of the beta3-AR ligands CL316243 and
      SR59230A showed that both can activate the mouse beta3-AR but that SR59230A uses
      pathways other than cAMP accumulation in 3T3-F442A cells. 5. Examination of a
      series of alpha1-AR agonists for their ability to activate a number of signalling
      pathways revealed that A61603 acted as a full agonist in all assays, whereas
      oxymetazoline was unable to cause cAMP accumulation, suggesting agonist-selective
      signalling at the human alpha1A-AR.

PMID- 15566402
TI  - Identification and characterization of the mouse and rat relaxin receptors as the
      novel orthologues of human leucine-rich repeat-containing G-protein-coupled
      receptor 7.
AB  - 1. Relaxin is an extracellular matrix (ECM)-remodelling hormone that is
      functionally important in reproductive tissues, brain, lung and heart. 2.
      Recently, the human relaxin receptor was identified as leucine-rich repeat
      containing G-protein-coupled receptor 7 (LGR7). 3. Using human LGR7 as a
      template, we identified mouse and rat LGR7 orthologues in the Celera and National
      Centre for Biotechnology Information databases. 4. At the protein level, mouse
      and rat LGR7 share 85.2 and 85.7% identity with human LGR7, respectively. 5.
      Mouse LGR7 mRNA was detected in all tissues where relaxin binding is observed. 6.
      Mouse and rat LGR7 bound [33P]-relaxin with high affinity and, upon relaxin
      treatment, both receptors stimulated cAMP production in transfected HEK 293T
      cells. 7. These results indicate that mouse and rat LGR7 are the relaxin
      receptors in these species. 8. The actions of relaxin in rodents are well
      characterized, providing an established platform for research into the molecular
      pharmacology of the highly conserved relaxin receptor.

PMID- 15566403
TI  - Interactions between delta opioid receptors and alpha-adrenoceptors.
AB  - 1. Several studies have reported functional interactions between different
      subtypes of opioid and alpha2A-adrenoceptors in the induction of spinal cord
      analgesia. The mechanisms underlying this phenomenon are not well characterized.
      We propose that direct receptor-receptor associations could account for some of
      the observed functional interactions. In the present study, we examined the
      presence of delta opioid receptors and alpha2A-adrenoceptors in interacting
      complexes and the functional implications of such interactions on receptor
      activity. 2. Using the proximity based bioluminescence resonance energy transfer
      (BRET) assay, we found that the delta opioid receptors and alpha2A-adrenoceptors
      are in close enough proximity (< 100 A) in live cells that can foster physical
      interactions. 3. Using coimmunoprecipitation of differentially epitope-tagged
      receptors, we found that delta opiate receptors exist in interacting complexes
      with alpha2A-adrenoceptors in heterologous cells. 4. Finally, using receptor
      activity mediated neurite outgrowth in Neuro 2A cells as a physiological readout,
      we found that interactions between delta opiate receptors and alpha2A
      adrenoceptors have functional consequences. The expression of alpha2A
      adrenoceptors is sufficient to promote delta opiate receptor-mediated neurite
      outgrowth, suggesting that the presence of inactive alpha2A-adrenoceptors can
      enhance delta opiate receptor-mediated signalling. 5. Taken together, these
      findings suggest that modulation of receptor function as a result of physical
      associations between delta opiate receptors and alpha2A-adrenoceptors may account
      for the observed synergy between opiate and adrenergic agonists in spinal
      analgesia.

PMID- 15566408
TI  - Proteoglycans and injury of the central nervous system.
AB  - Proteoglycan is a family of glycoproteins which carry covalently-linked
      glycosaminoglycan chains, such as chondroitin sulfate and heparan sulfate.
      Proteoglycans are believed to play important roles in morphogenesis and
      maintenance of various tissues including the central nervous system (CNS) through
      interactions with cell adhesion molecules and growth factors. In the CNS, a
      significant amount of evidence has been accumulated to show that proteoglycans
      function as modulators in various cellular events not only in the development,
      but also in the pathogenesis of neuronal diseases and lesions. When the CNS is
      injured, several chondroitin sulfate proteoglycans (CSPG) are up-regulated in
      glial scars formed around the lesion site. The glial scar also contains some
      molecules inhibitory to axonal growth, such as myelin-associated glycoprotein,
      Nogo, and Semaphorin. In vitro studies revealed that CSPG largely exert a
      repulsive effect on axonal regeneration, and a signal from CSPG modulates the
      actin cytoskeleton of outgrowing neurites through the Rho/ROCK pathway. These
      findings suggest that CSPG are responsible for unsuccessful axonal regeneration
      in glial scars. Various attempts to overcome the inhibitory effect of CSPG have
      been pursued in vivo. Digestion of chondroitin sulfate chains by chondroitinase
      ABC, suppression of CSPG core protein synthesis by decorin, suppression of
      glycosaminoglycan chain synthesis by a DNA enzyme, and inhibition of the Rho/ROCK
      pathway with specific inhibitors were all successful for increasing axonal
      regeneration. For a clinical application, the most effective combination of these
      treatments needs to be examined in the future.

PMID- 15566409
TI  - Purkinje cell loss in the cerebellum of ataxic mutant mouse, dilute-lethal: a
      fractionator study.
AB  - This study estimated total number of Purkinje cells in the cerebellum of an
      ataxic mutant mouse, dilute-lethal (DL), with reference to severe ataxic symptoms
      of this mutant. On postnatal day (PD) 21, the cerebellar weight is significantly
      lower in DL than in non-ataxic littermates (control mice). Total number of
      Purkinje cells is also significantly lower in DL than in the controls;
      approximately 25% less in DL than in the controls. Furthermore, we performed in
      situ nick end labeling (TUNEL) -staining in the cerebellum of DL during prenatal
      and postnatal periods in order to examine the cause of the reduced Purkinje cell
      number. For analyzes of the mutant fetuses, it is necessary to identify the
      homozygous mutant. We succeeded in identifying the homozygous DL fetuses from the
      control fetuses (wild-type or heterozygous fetuses) by the hair color of the
      grafted skin pieces on nude mice. The histological features of the cerebellar
      primordium did not differ between the DL and controls on embryonic and postnatal
      ages examined. In DL, a significantly greater number of TUNEL-positive Purkinje
      cells was detected on embryonic day (ED) 12, but not throughout ED 14 to PD 21.
      The results suggest that the Purkinje cell loss in the DL cerebellum is
      attributed to increased apoptotic cell death of the progenitors. This may be
      involved in the development of severe ataxic symptoms of DL.

PMID- 15566410
TI  - Studies on preliminary concentration methods for recovery of fetal nucleated red
      blood cells in maternal blood.
AB  - Non-invasive prenatal diagnostic methods posing no danger to the embryo have been
      desired for many years in the field of prenatal medicine. We are in the process
      of improving the lectin method that we developed for recovering fetus-derived
      nucleated red blood cells (NRBC) in the maternal peripheral blood. We previously
      used Ficoll density-gradient centrifugation for preliminary concentration in the
      lectin method. In the present study, we developed a molecular filter method,
      compared it with the Ficoll method, and tested its applicability to prenatal
      diagnosis. We tested the usefulness of a high molecular filter method for
      preliminary concentration. First, in a basic study, we prepared three kinds of
      non-woven cloth (NWC1-3) and a multi-porous filter (MP) to determine the optimal
      filter. Next, we compared the recovery rates of the Ficoll and filter methods as
      preliminary concentration methods in 34 normal pregnant women. Then, to examine
      whether the recovered NRBC were derived from the fetus, we attempted prenatal
      diagnosis by the fluorescence in situ hybridization (FISH) technique in 12 women
      pregnant with a male fetus (determined later by ultrasound) at between 8 and 16
      weeks of gestation. Among the four devices used in the basic study of the high
      molecular filter method, NWC-2 had the best recovery rate. Therefore, we compared
      the numbers of NRBC recovered by the lectin method after preliminary
      concentration with NWC-2 or by Ficoll centrifugation, and found that the mean
      recovery rate of NWC-2 was 4.2 +/- 5.0 times as high as that of the Ficoll
      method, indicating that the NWC-2 filter method is superior as a preliminary
      concentration method. Next, FISH analysis of the 12 pregnant women with a male
      fetus for the Y chromosome showed that 19.5 +/- 12.8 NRBC were recovered, in 12.7
      +/- 8.1 (63.6%) of which a Y signal was confirmed, suggesting the NWC-2 filter
      method can be applied to prenatal diagnosis. We consider the filter-lectin method
      to be a superior method for isolation and recovery of NRBC in the maternal blood
      which can be applied to prenatal diagnosis.

PMID- 15566411
TI  - Comparative toxicity study of 2,4,6-trinitrophenol (picric acid) in newborn and
      young rats.
AB  - The toxicity of oral 2,4,6-trinitrophenol (TNP) was determined in newborn rats,
      and compared with that in young rats. In newborn rats, males and females were
      given TNP at 0, 16.3, 81.4 or 407 mg/kg per day on postnatal days (PND) 4-17 for
      the dose-finding study, and at 0, 4.1, 16.3 or 65.1 mg/kg per day on PND 4-21 for
      the main study. Deaths, lower body weight (BW) and behavioral changes were found
      at 81.4 and 407 mg/kg per day in the dose-finding study, and lower BW was
      observed in males at 65.1 mg/kg per day during the dosing period of the main
      study. In young rats, 5-week-old males and females were given TNP at 0, 20, 100
      or 500 mg/kg per day for 14 days as the dose-finding study and at 0, 4, 20 or 100
      mg/kg per day for 28 days as the main study. Deaths were observed at 500 mg/kg
      per day in the dose-finding study. Deaths or changes in BW were not found at 100
      mg/kg per day or less. At 100 mg/kg per day, hemolytic anemia and testicular
      toxicity were found. In conclusion, toxicity profiles induced by TNP were
      markedly different between newborn and young rats.

PMID- 15566412
TI  - Expression of SV40 T antigen gene in the oligodendroglia induced primitive
      neuroectodermal tumor-like tumors in the mouse brain.
AB  - Primitive neuroectodermal tumors (PNET) are classified as the embryonal tumors
      developed in the brain, except for the cerebellum. Although many studies have
      been reported, the origin and pathogenesis of PNET are still unclear. In this
      study, we observed the development of undifferentiated tumors indistinguishable
      from PNET in the transgenic mice which expressed simian virus 40 T antigen (SV40
      Tag) selectively in the oligodendroglia under the control of mouse myelin basic
      protein gene promoter. These PNET-like tumors reproducibly developed in the brain
      stem of the founder mice and the transgenic progeny derived from one founder
      mouse. Oligodendroglia-specific expression of SV40-Tag in these transgenic mice
      was observed by immunohistochemical analysis. Furthermore, expression of the
      oligodendroglia-specific marker genes was decreased in the tumors as well as in
      the transgenic brains. These findings suggested that tumors developed in
      transgenic mice were indistinguishable from PNET, and one of them showed
      oligodendroglia-like characteristics. Consequently, this transgenic line is a
      useful animal model to study the pathogenesis of undifferentiated tumor.

PMID- 15566413
TI  - Large fontanelles are a shared feature of haploinsufficiency of RUNX2 and its co
      activator CBFB.
AB  - CBFB at 16q22 heterodimerizes with either RUNX2 (also known as CBFA1) or RUNX1
      (CBFA2) to activate the transcription of downstream molecules. RUNX2 regulates
      osteoblast differentiation and chondrocyte maturation and its haploinsufficiency
      leads to cleidocranial dysplasia, characterized large fontanelles, hypoplasia or
      aplasia of the clavicles, hypoplasia of the distal phalanges, and a wide pubic
      symphysis. Complete loss of Runx1 or Cbfb in mice is lethal because of the
      absence of fetal liver hematopoiesis. Fetal rescue in Cbfb(-/-) mice by providing
      the Cbfb functions in the hematopoietic progenitors leads to wide fontanelle and
      delayed chondrocyte maturation, presumably resulting from the incomplete function
      of the transcriptional pathway mediated by the Cbfb-Runx2 heterodimer. The
      present report describes a patient with a small deletion of chromosome 16q22.1
      encompassing CBFB. Skeletal abnormalities included a widely open fontanelle,
      multiple wormian bones along the sagittal suture, hypoplasia of the distal
      phalanges, and mildly shortened clavicles. G-banding analysis revealed a
      shortening of the 16q22.1 band. A fluorescence in situ hybridization analysis,
      using the BAC probe spanning the CBFB locus at 16q22.1, revealed that the CBFB
      probe hybridized to only one of the two homologous chromosome 16 regions. Array
      comparative genomic hybridization analysis revealed that the deletion spans 1.2
      megabases. In reviewing eight previously reported cases of 16q interstitial
      deletions involving band q22, large cranial sutures were noted in all but one
      case. Considering the phenotypic similarity of the 16q22 deletion case and Cbfb(
      /-) mice rescued for hematopoiesis and the consistency of the phenotype among
      16q22 deletion cases, we suggest that the common phenotypic feature of the 16q22
      deletion, large fontanelles, can be attributed to a haploinsufficiency of CBFB.

PMID- 15566414
TI  - Is migraine really comorbid with systemic lupus erythematosus?

PMID- 15566415
TI  - Sporadic hemiplegic migraine.
AB  - Sporadic hemiplegic migraine (SHM) is defined as migraine attacks associated with
      some degree of motor weakness/hemiparesis during the aura phase and where no
      first degree relative (parent, sibling or child) has identical attacks. The
      present review deals with recent scientific studies according to which: The SHM
      prevalence is estimated to be 0.005%; SHM patients have clinical symptoms
      identical to patients with familial hemiplegic migraine (FHM) and significantly
      different from patients with migraine with typical aura (typical MA); SHM
      affected had no increased risk of migraine without aura (MO), but a highly
      increased risk of typical MA compared to the general population; SHM patients
      only rarely have mutations in the FHM gene CACNA1A; SHM attacks in some cases can
      be treated with Verapamil. The reviewed data underlie the change in the
      International Classification of Headache Disorders 2nd edition where SHM became
      separated from migraine with typical aura or migraine with prolonged aura. All
      cases with motor weakness should be classified as either FHM or SHM.

PMID- 15566416
TI  - Clinical implications of migraine in systemic lupus erythematosus: relation to
      cumulative organ damage.
AB  - The aim of this study was to determine the clinical implications of migraine in
      systemic lupus erythematosus (SLE) using the cumulative organ damage scores
      (SLICC-DI). Eighty SLE, 40 rheumatoid arthritis (RA) patients and 40 controls
      (non SLE, nor RA out-patients), all women, were included. Migraine was defined
      according to the International Headache Society (IHS) criteria for
      neuropsychiatric SLE. Disease activity was measured by MEX-SLEDAI and cumulative
      organ damage by SLICC-DI. Statistics were obtained by Chi-square and Fischer's
      exact tests. anova was used for comparing means. Migraine was identified in 42.5%
      of SLE patients, compared to 12.5% of RA patients (P < 0.05) and 10.0% (P < 0.05)
      in the control group. In the SLE group, a significant association between
      migraine and Raynaud's phenomenon (P = 0.003, OR = 10.1; 95%CI 2.9-35) and
      antiphospholipid antibodies (P = 0.0012; OR = 7.5; 95%CI 2.5-22.9) was noted. SLE
      patients with active migraine had higher MEX-SLEDAI scores than SLE patients
      without migraine. SLE patients with past history of migraine had significantly
      higher SLICC scores than SLE patients without migraine. History of migraine was
      associated with greater organ damage. Active migraine was associated with higher
      disease activity, antiphospholipid antibodies and worsening of Raynaud's
      phenomenon. The increased cumulative organ damage in SLE patients with past
      history of migraine justifies the routine evaluation of migraine in clinical
      practice.

PMID- 15566417
TI  - Prevalence and factors associated with headache in patients with systemic lupus
      erythematosus.
AB  - Headache is common in systemic lupus erythematosus with reported prevalence as
      high as 70%. The aims of this study were: to estimate the prevalence and types of
      headache in a sample of patients with systemic lupus erythematosus comparing it
      with rheumatoid arthritis, to determine clinical and serological associations.
      Eighty-one systemic lupus erythematosus and 29 rheumatoid arthritis consecutive
      patients seen in our outpatient clinic were interviewed. Headache was evaluated
      using the diagnostic criteria proposed by the International Headache Society.
      Additional evaluations were carried out in the 81 systemic lupus erythematosus
      patients including depression, disease activity, lupus damage, function
      disability, quality of life, and severity degree using a validated scales. We
      analysed the following autoantibodies: anti-double stranded DNA, anti
      nucleosomes, anti-histones, anti-ribosomal P, anti-cardiolipin antibodies, anti
      beta2-glycoprotein-I (GPI), and antinuclear antibodies. Forty-one per cent of
      systemic lupus erythematosus and 17% of rheumatoid arthritis patients suffered
      from headache (P = 0.02). No significant difference for any primary headache type
      between the two groups was found. Frequency of headache types in systemic lupus
      erythematosus patients was: migraine 24%, tensional-type headache 11%, and mixed
      headache 5%. In systemic lupus erythematosus patients the risk factors associated
      with headaches were Raynaud's phenomenon (OR 3.6; 95% CI 1.3-9.5; P = 0.009) and
      beta2GPI antibody positivity (OR 4.5; 95% CI 1.2-16.2; p = 0.016). We conclude
      that headache is more common in systemic lupus erythematosus than in rheumatoid
      arthritis patients and was independently associated with Raynaud's phenomenon and
      beta2GP-I antibodies.

PMID- 15566418
TI  - Frovatriptan for the treatment of cluster headaches.
AB  - Cluster headaches both episodic and chronic are some of the most challenging
      headaches to treat. Although effective treatments are now available, some
      patients continue to be unresponsive to standard therapy. We present 17 patients
      from our practice whom we treated preventively with frovatriptan, a new triptan
      with a long half-life. The promising results suggest that this medication may be
      an useful addition to our ammaterium against this painful disorder.

PMID- 15566419
TI  - Topiramate inhibits trigeminovascular neurons in the cat.
AB  - To facilitate understanding the action of antimigraine preventives the effect of
      topiramate on trigeminocervical activation in the cat was examined. Animals (n =
      7) were anaesthetized and physiologically monitored. The superior sagittal sinus
      (SSS) was stimulated to produce a model of trigeminovascular nociceptive
      activation. Cumulative dose-response curves were constructed for the effect of
      topiramate at doses of 3, 5, 10, 30 and 50 mg/kg on SSS-evoked firing of
      trigeminocervical neurons. Topiramate reduced SSS evoked firing in a dose
      dependent fashion. The maximum effect was seen over 30 min for the cohort taken
      together. At 3 mg/kg firing was reduced by 36 +/- 13% (mean +/- SEM) after 15
      min. At 5 and 50 mg/kg firing was reduced by 59 +/- 6% and 65 +/- 14%,
      respectively, after 30 min. Inhibition of the trigeminocervical complex directly,
      or neurons that modulate sensory input, are plausible mechanisms for the action
      of preventives in migraine.

PMID- 15566420
TI  - Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.
AB  - Unpleasant sensory symptoms are commonly reported in association with the use of
      5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the
      chest and neck have restricted the use of triptans in the acute treatment of
      migraine. The cause of these triptan induced side-effects is still unidentified.
      We have now tested the hypothesis that sumatriptan influences the perception of
      tactile and thermal stimuli in humans in a randomized, double-blind, placebo
      controlled cross-over study. Two groups were tested; one consisted of 12 (mean
      age 41.2 years, 10 women) subjects with migraine and a history of cutaneous
      allodynia in association with sumatriptan treatment. Twelve healthy subjects
      (mean age 38.7 years, 10 women) without migraine served as control group. During
      pain- and medication-free intervals tactile directional sensibility, perception
      of dynamic touch (brush) and thermal sensory and pain thresholds were studied on
      the dorsal side of the left hand. Measurements were performed before, 20, and 40
      min after injection of 6 mg sumatriptan or saline. Twenty minutes after
      injection, sumatriptan caused a significant placebo-subtracted increase in brush
      evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush
      evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold
      in all participants pooled (P = 0.031), and a reduction of cold pain threshold in
      controls only (P = 0.013). At 40 min after injection, no differences remained
      significant. There were no changes in ratings of brush intensity, tactile
      directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan
      may cause a short-lasting allodynia in response to light dynamic touch and a
      reduction of heat and cold pain thresholds. This could explain at least some of
      the temporary sensory side-effects of triptans and warrants consideration in the
      interpretation of studies on migraine-induced allodynia.

PMID- 15566421
TI  - Quantification of acute neck pain following whiplash injury by computer-aided
      pressure algesimetry.
AB  - Until now the clinical investigation of cervical pain due to whiplash injury is
      mainly based on finger palpation. The present study introduces a PC-interactive
      pressure algesimetry to standardize cervical pain measurement. Pressure pain
      scores of the splenius and trapezius muscles of 23 patients with an acute
      cervical syndrome after whiplash injury were compared to those of 24 healthy
      subjects. The pressure painfulness of neck and shoulder muscles was significantly
      increased in whiplash patients. The splenii muscles showed an equally increased
      muscle pain whereas the trapezii muscles showed a left-sided preponderance of
      painfulness, possibly due to the seat belt position in this group of motor
      vehicle drivers. The computer-interactive pressure algesimetry enables a
      standardized and rater-independent quantification of the cervical syndrome with
      neck and shoulder pain caused by whiplash injury.

PMID- 15566422
TI  - The effect of propranolol on glyceryltrinitrate-induced headache and arterial
      response.
AB  - Prophylactic drug trials in migraine are long-lasting and expensive and require
      long-term toxicology information. A human migraine model would therefore be
      helpful in testing new drugs. Immediate headache and delayed migraine after
      glyceryltrinitrate (GTN) has been well characterized. We have recently shown that
      sodium valproate has prophylactic effect in the GTN model. Here we report our
      experience with propranolol in this model. Nineteen subjects with migraine
      without aura and 16 sex- and aged-matched healthy subjects were included in a two
      centre randomized double-blind cross-over study. Fourteen migraine subjects and
      14 healthy subjects completed the study and results from comparison of the 28
      subjects are reported. Randomly propranolol 160 mg or placebo were each given
      daily for 14 days to both migraine and healthy subjects. A 20-min intravenous
      infusion of GTN 0.25 microg/kg per min was administered on a study day at the end
      of both pretreatment periods. Headache was registered for 12 h after GTN
      infusions. Its intensity was scored on a numerical verbal rating scale from 0 to
      10. Fulfilment of International Headache Society (HIS) criteria was recorded for
      24 h. Radial and superficial temporal artery diameters and blood velocity of both
      middle cerebral arteries were measured. All migraine subjects developed headache
      after GTN. No reduction of overall peak headache was found after propranolol
      (median 5, range 0-7) compared with placebo (median 5, range 0-10) (P = 0.441).
      Eight of the 14 completing migraine subject developed IHS 1.1 migraine after GTN,
      two subjects on both days, three subjects only after placebo, and three subjects
      only after propranolol. No reduction of GTN-induced migraine was found after
      propranolol compared with placebo (5 vs. 5, P = 1.000). All healthy subjects
      developed headache after GTN. No reduction of overall peak headache was found
      after propranolol (median 2, range 1-5) compared with placebo (median 1, range 1
      7) (P = 0.315). Two subjects fulfilled IHS criteria 1.1 for migraine without aura
      after propranolol but not after placebo. The fulfilment was short lasting and did
      not require rescue medication. Headache after GTN was more pronounced in migraine
      subjects than in healthy subjects both with (P = 0.003) and without pretreatment
      with propranolol (P = 0.017). We found that 2 weeks of propranolol constricted
      the radial artery in healthy subjects but not in migraine subjects. GTN-induced
      vasodilatation abolished this difference. Mean maximum blood flow velocity in the
      middle cerebral artery was higher in healthy subjects than in migraine patients
      (P = 0.003-0.033) and unaffected by propranolol. We observed no effect of
      propranolol on GTN-induced headache and migraine. This could indicate that GTN
      induces migraine at a deeper level of the pathophysiological cascade of migraine
      than the prophylactic effect of propranolol. Propranolol does not constrict
      cerebral arteries, which therefore cannot be part of its mechanism of action in
      migraine.

PMID- 15566423
TI  - Cluster-tic syndrome resolved by removal of pituitary adenoma: the first case.

PMID- 15566428
TI  - Regulation of growth signalling and cell cycle by Kaposi's sarcoma-associated
      herpesvirus genes.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the primary aetiological agent
      of at least three malignancies associated with HIV infection and
      immunosuppression: Kaposi's sarcoma, primary effusion lymphoma and multicentric
      Castleman's disease. KSHV encodes proteins that deregulate key checkpoints in the
      signalling pathways governing cell proliferation, which may ultimately contribute
      to the virus' oncogenic potential. To alter cellular signalling associated with
      proliferation, these viral proteins function like growth factor
      ligands/receptors, signal transduction proteins, transcription factors and cell
      cycle regulators. This review focuses on the mechanisms by which some KSHV
      encoded proteins activate signalling pathways and cell proliferation and their
      role in the pathogenesis of KSHV-driven mechanisms.

PMID- 15566429
TI  - Down-regulation of pathogenic autoantibody response in a slowly progressive
      Heymann nephritis kidney disease model.
AB  - In the present article, we describe an antigen-specific down-regulation of a
      pathogenic autoantibody (aab)-mediated disease process in an experimental
      autoimmune kidney disease in rats called slowly progressive Heymann nephritis
      (SPHN). This autoimmune disease is initiated and maintained by pathogenic
      immunoglobulin G (IgG) autoantibodies (aabs), which cause an immune-complex (IC)
      glomerulonephritis associated with proteinuria. We achieved down-regulated
      pathogenic aab response in SPHN rats by injections of an IC containing the native
      nephritogenic antigen and specific high-titred nonpathogenic IgM aabs, in antigen
      excess. The injected IC increased the level of circulating nonpathogenic IgM
      aabs; the increased levels of specific IgM aabs in turn facilitated the removal
      of the injected altered nephritogenic and liberated autoantigens from the renal
      tubules and greatly diminished the production of pathogenic aabs and the build up
      of immune deposits in the glomeruli. While animals treated early had advantages
      over rats whose kidney disease was well established before treatment; animals
      treated late into the disease still manifested noticeable improvements in similar
      areas, i.e. with lessened proteinuria, kidney lesion reduction and a decreased
      pathogenic aab response. At the end of the experiment at 29 weeks, 80% of all the
      treated rats had insignificantly low levels of circulating IgG aabs, indicating
      cessation of pathogenic aab production and corresponding termination of the
      disease process. In contrast, most untreated rats with the kidney disease still
      had high levels of circulating pathogenic aabs at the end of the experiment,
      which maintained disease progression.

PMID- 15566430
TI  - Induction of macrophage scavenger receptor MARCO in nonalcoholic steatohepatitis
      indicates possible involvement of endotoxin in its pathogenic process.
AB  - Nonalcoholic steatohepatitis (NASH) is one of the life-threatening hepatic
      diseases; however, its pathogenesis is still unknown. To evaluate the causative
      role of hyperlipidaemia and high-fat diet, we compared C57BL/6 mice with
      inherited hyperlipidaemic model mice (LDLR(-/-)mice and ApoE(-/-) mice) fed a
      normal or a high-fat diet. LDLR(-/-) and ApoE(-/-) mice fed the normal diet
      showed significantly higher serum cholesterol level than that of C57BL/6 mice fed
      the high-fat diet. These mice, however, have shown neither significant elevation
      of serum alanine transaminase (ALT) level nor histopathologic features of
      steatohepatitis. High-fat diet groups of all three strains showed
      histopathological characteristics of steatohepatitis with elevated serum ALT
      levels and high expression of macrophage scavenger receptor MARCO mRNA in the
      liver. Semiquantitative endotoxin analysis showed an elevated serum endotoxin
      level in the portal vein but not in the vena cava in ApoE(-/-) mice fed the high
      fat diet. These results indicate that long-term feeding of a high-fat diet
      induces NASH, whereas hyperlipidaemia alone is not enough to induce NASH. Liver
      restricted induction of MARCO in mice with high-fat diet and portal endotoxaemia
      in ApoE(-/-) mice fed the high-fat diet suggest the possible involvement of
      endotoxin in the pathogenesis of NASH.

PMID- 15566431
TI  - The role of tumour necrosis factor-alpha in renal dysfunction following mild
      haemorrhage in rats.
AB  - Mild haemorrhage occasionally causes delayed death following failure of kidney or
      multiple organs, but the precise mechanisms have not yet been identified. We
      investigated the role of tumour necrosis factor-alpha (TNF-alpha), known as a
      major pro-inflammatory cytokine that leads to multiple organ failure, on the
      renal damage induced by mild haemorrhage. A mild haemorrhagic state was induced
      in male anaesthetized rats by bleeding via a common carotid catheter for 20 min
      at 16.7% of total body blood, 1.09 ml/100 g body weight, without fluid
      resuscitation. Mean arterial pressure and heart rate decreased soon after
      haemorrhaging but returned to baseline level up to 5 h after bleeding. TNF-alpha
      mRNA expression in the kidney and serum TNF-alpha levels were highest at 1 h
      after bleeding. Intraperitoneal pretreatment with FR167653, an inhibitory
      compound of TNF-alpha production, as well as of interleukin (IL)-1beta,
      significantly inhibited the increase in TNF-alpha. The inflammatory cell
      infiltration and tubular cell injury induced by haemorrhage were suppressed, and
      the renal dysfunction was dramatically improved by the FR167653 treatment. The
      morphological changes were also less in the treated group than in those that had
      not been treated. TNF-alpha has been reported to have striking effects on IL
      1beta release and activation of neutrophils, and to play a pivotal role in the
      expression of the other pro-inflammatory cytokines. Our data show that
      endogenously-derived TNF-alpha does play a key role in the renal dysfunction
      during mild haemorrhage. These results should be useful to forensic pathologists
      to explain the pathogenesis of renal dysfunction induced by a mild haemorrhage
      and to identify the cause of death where there are no significant morphological
      changes after mild haemorrhage.

PMID- 15566432
TI  - Vascular endothelial growth factor reduces mural cell coverage of endothelial
      cells and induces sprouting rather than luminal division in an HT1080 tumour
      angiogenesis model.
AB  - Vascular endothelial growth factor (VEGF) plays a central role in tumour
      angiogenesis. In a mouse intramuscular tumour model using VEGF-transfected HT1080
      human fibrosarcoma, we investigated the morphological features and patterns of
      remodelling in size-matched tumours. Compared with the control tumours (C group),
      the VEGF-transfected tumours (V group) showed vigorous neovascularization with
      larger vessels. Fenestrations and disruptions of endothelia were specific to the
      V group. Three types of vascular remodelling, i.e. sprouting, luminal division
      and intussusceptive microvascular growth, were present in both groups.
      Morphometric analyses revealed that mural cell coverage of the endothelial cells
      was significantly smaller in the V group compared with that in the C group (V
      group, 28.2 +/- 18.6%; C group, 41.6 +/- 21.1%; P < 0.0001). To determine the
      prevalence of remodelling patterns, the occurrences of abluminal and luminal
      processes on endothelial cell surfaces were quantified. Abluminal processes are
      defined as cytoplasmic protrusions of the abluminal membrane of endothelial
      cells, which can vary from tiny spurs to solid sprouts of the cell. On the other
      hand, luminal processes are defined as intraluminal protrusions of the
      endothelial cell membrane, including various membranous changes from filiform
      processes to rather thick cytoplasmic bulges. An abluminal process is thought to
      represent an initial morphological change in sprouting type angiogenesis, and a
      luminal process to be a sign of implementation of luminal division. The frequency
      of abluminal processes was significantly higher in the V group than in the C
      group (V group, 0.243 +/- 0.138/microm; C group, 0.114 +/- 0.101/microm; P <
      0.0001). In contrast, the number of luminal processes on the endothelial cells
      per micrometre was statistically comparable between the groups (V group, 0.285 +/
      0.252/microm; C group, 0.309 +/- 0.236/microm, P = 0.381). These results
      indicate that sprouting is the main mode of VEGF-induced tumour angiogenesis.

PMID- 15566433
TI  - Effects of proteasome inhibitors MG132, ZL3VS and AdaAhx3L3VS on protein
      metabolism in septic rats.
AB  - Proteasome inhibitors are novel therapeutic agents for the treatment of cancer
      and other severe disorders. One of the possible side effects is influencing the
      metabolism of proteins. The aim of our study was to evaluate the influence of
      three proteasome inhibitors MG132, ZL(3)VS and AdaAhx(3)L(3)VS on protein
      metabolism and leucine oxidation in incubated skeletal muscle of control and
      septic rats. Total proteolysis was determined according to the rates of tyrosine
      release into the medium during incubation. The rates of protein synthesis and
      leucine oxidation were measured in a medium containing L-[1-(14)C]leucine.
      Protein synthesis was determined as the amount of L-[1-(14)C]leucine incorporated
      into proteins, and leucine oxidation was evaluated according to the release of
      (14)CO(2) during incubation. Sepsis was induced in rats by means of caecal
      ligation and puncture. MG132 reduced proteolysis by more than 50% and protein
      synthesis by 10-20% in the muscles of healthy rats. In septic rats, proteasome
      inhibitors, except ZL(3)VS, decreased proteolysis in both soleus and extensor
      digitorum longus (EDL) muscles, although none of the inhibitors had any effect on
      protein synthesis. Leucine oxidation was increased by AdaAhx(3)L(3)VS in the
      septic EDL muscle and decreased by MG132 in intact EDL muscle. We conclude that
      MG132 and AdaAhx(3)L(3)VS reversed protein catabolism in septic rat muscles.

PMID- 15566434
TI  - Co-stimulation of human breast cancer cells with transforming growth factor-beta
      and tenascin-C enhances matrix metalloproteinase-9 expression and cancer cell
      invasion.
AB  - Transforming growth factor-beta (TGF-beta), tenascin-C (TN-C) and matrix
      metalloproteinases (MMPs) have been demonstrated independently to be associated
      with disease progression and poor prognosis in patients with breast cancer. The
      present study explored effects of TGF-beta and TN-C on MMP-9 expression and
      cancer invasion. An experimental study was designed to analyse MDA-MB-231 breast
      cancer cells, known for their high invasiveness, after stimulation with TGF-beta1
      and/or TN-C. TGF-beta1 stimulated TN-C expression in the cells. Co-stimulation of
      MDA-MB-231 cells with TN-C and TGF-beta increased MMP-9 expression at both the
      gene (28-fold) and the protein levels. The in vitro invasion also increased (4
      fold). GM6001 inhibited the invasion induced by the co-stimulation. The combined
      effect of TN-C and TGF-beta resulted in enhanced MMP-9 expression and cancer
      invasion in vitro.

PMID- 15566435
TI  - Patient-centered communication: do patients really prefer it?
AB  - OBJECTIVE: To investigate patient preferences for a patient-centered or a
      biomedical communication style. DESIGN: Randomized study. SETTING: Urgent care
      and ambulatory medicine clinics in an academic medical center. PARTICIPANTS: We
      recruited 250 English-speaking adult patients, excluding patients whose medical
      illnesses prevented evaluation of the study intervention. INTERVENTION:
      Participants watched one of three videotaped scenarios of simulated patient
      physician discussions of complementary and alternative medicine (CAM). Each
      participant watched two versions of the scenario (biomedical vs. patient-centered
      communication style) and completed written and oral questionnaires to assess
      outcome measurements. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were
      1) preferences for a patient-centered versus a biomedical communication style;
      and 2) predictors of communication style preference. Participants who preferred
      the patient-centered style (69%; 95% confidence interval [CI], 63 to 75) tended
      to be younger (82% [51/62] for age < 30; 68% [100/148] for ages 30-59; 55%
      [21/38] for age > 59; P < .03), more educated (76% [54/71] for postcollege
      education; 73% [94/128] for some college; 49% [23/47] for high school only; P=
      .003), use CAM (75% [140/188] vs. 55% [33/60] for nonusers; P= .006), and have a
      patient-centered physician (88% [74/84] vs. 30% [16/54] for those with a
      biomedical physician; P < .0001). On multivariate analysis, factors independently
      associated with preferring the patient-centered style included younger age, use
      of herbal CAM, having a patient-centered physician, and rating a "doctor's
      interest in you as a person" as "very important." CONCLUSIONS: Given that a
      significant proportion of patients prefer a biomedical communication style,
      practicing physicians and medical educators should strive for flexible approaches
      to physician-patient communication.

PMID- 15566436
TI  - Do unmet expectations for specific tests, referrals, and new medications reduce
      patients' satisfaction?
AB  - BACKGROUND: Patient-centered care requires clinicians to recognize and act on
      patients' expectations. However, relatively little is known about the specific
      expectations patients bring to the primary care visit. OBJECTIVE: To describe the
      nature and prevalence of patients' specific expectations for tests, referrals,
      and new medications, and to examine the relationship between fulfillment of these
      expectations and patient satisfaction. DESIGN: Prospective cohort study. SETTING:
      VA general medicine clinic. PATIENTS/PARTICIPANTS: Two hundred fifty-three adult
      male outpatients seeing their primary care provider for a scheduled visit.
      MEASUREMENTS AND MAIN RESULTS: Fifty-six percent of patients reported at least 1
      expectation for a test, referral, or new medication. Thirty-one percent had 1
      expectation, while 25% had 2 or more expectations. Expectations were evenly
      distributed among tests, referrals, and new medications (37%, 30%, and 33%,
      respectively). Half of the patients who expressed an expectation did not receive
      one or more of the desired tests, referrals, or new medications. Nevertheless,
      satisfaction was very high (median of 1.5 for visit-specific satisfaction on a 1
      to 5 scale, with 1 representing "excellent"). Satisfaction was not related to
      whether expectations were met or unmet, except that patients who did not receive
      desired medications reported lower satisfaction. CONCLUSIONS: Patients'
      expectations are varied and often vague. Clinicians trying to implement the
      values of patient-centered care must be prepared to elicit, identify, and address
      many expectations.

PMID- 15566437
TI  - Satisfaction with the outpatient encounter: a comparison of patients' and
      physicians' views.
AB  - OBJECTIVE: To compare patients' and physicians' visit-specific satisfaction in an
      internal medicine outpatient setting, and to explain their respective views.
      DESIGN: Patients' and physicians' background characteristics were assessed prior
      to outpatient encounters. Immediately after the encounter, both patients and
      physicians completed a questionnaire assessing satisfaction with the visit.
      SETTING: The outpatient division of an academic teaching hospital. PARTICIPANTS:
      Thirty residents and specialists in general internal medicine, rheumatology, and
      gastroenterology, and 330 patients having a follow-up appointment with one of
      these physicians. MEASUREMENTS AND MAIN RESULTS: Patients' and physicians' visit
      specific satisfaction was assessed using 5 Visual Analogue Scales (0 to 100).
      Patients' overall satisfaction was higher than physicians' satisfaction (mean 81
      vs. 66), and correlation of patients' and physicians' overall satisfaction with
      the specific visit was medium sized (r= .28, P < .001). Patients' satisfaction
      ratings were associated with their previsit self-efficacy in communicating with
      their physician (P < .001) and with visiting a female physician (P < .01).
      Physicians' satisfaction was associated with patients' higher educational level
      (P < .05), primary language being Dutch (P < .001), better mental health (P <
      .05), and preference for receiving less than full information (P < .05).
      CONCLUSIONS: In an outpatient setting, patients' visit-specific satisfaction
      ratings were substantially higher than, and only moderately associated with,
      physicians' ratings of the same visit. The dissimilar predictors explaining
      patients' and physicians' satisfaction suggest that patients and physicians form
      their opinion about a consultation in different ways. Hence, when evaluating
      outpatient encounters, physicians' satisfaction has additional value to patients'
      satisfaction in establishing quality of care.

PMID- 15566438
TI  - Better physician-patient relationships are associated with higher reported
      adherence to antiretroviral therapy in patients with HIV infection.
AB  - BACKGROUND: There is little evidence to support the widely accepted assertion
      that better physician-patient relationships result in higher rates of adherence
      with recommended therapies. OBJECTIVE: To determine whether and which aspects of
      a better physician-patient relationship are associated with higher rates of
      adherence with antiretroviral therapies for persons with HIV infection. DESIGN:
      Cross-sectional analysis. SETTING: Twenty-two outpatient HIV practices in a
      metropolitan area. PARTICIPANTS: Five hundred fifty-four patients with HIV
      infection taking antiretroviral medications. MEASUREMENTS: We measured adherence
      using a 4-item self-report scale (alpha= 0.75). We measured core aspects of
      physician-patient relationships using 6 previously tested scales (general
      communication, HIV-specific information, participatory decision making, overall
      satisfaction, willingness to recommend physician, and physician trust; alpha >
      0.70 for all) and 1 new scale, adherence dialogue (alpha= 0.92). For adherence
      dialogue, patients rated their physician at understanding and solving problems
      with antiretroviral therapy regimens. RESULTS: Mean patient age was 42 years, 15%
      were female, 73% were white, and 57% reported gay or bisexual sexual contact as
      their primary HIV risk factor. In multivariable models that accounted for the
      clustering of patients within physicians' practices, 6 of the 7 physician-patient
      relationship quality variables were significantly (P < .05) associated with
      adherence. In all 7 models worse adherence was independently associated (P < .05)
      with lower age, not believing in the importance of antiretroviral therapy, and
      worse mental health. CONCLUSIONS: This study showed that multiple, mutable
      dimensions of the physician-patient relationship were associated with medication
      adherence in persons with HIV infection, suggesting that physician-patient
      relationship quality is a potentially important point of intervention to improve
      patients' medication adherence. In addition, our data suggest that it is critical
      to investigate and incorporate patients' belief systems about antiretroviral
      therapy into adherence discussions, and to identify and treat mental disorders.

PMID- 15566439
TI  - Patient-reported and physician-estimated adherence to HAART: social and clinic
      center-related factors are associated with discordance.
AB  - OBJECTIVES: To evaluate the rate of discordance between patients and physicians
      on adherence to highly active antiretroviral therapy (HAART) and identify factors
      related to discordance in these two assessments. DESIGN: Prospective,
      multicenter, cohort study (AdICONA) nested within the Italian Cohort Naive
      Antiretrovirals (ICONA) study. SETTING: Tertiary clinical centers. PARTICIPANTS:
      The patients filled out a 16-item self-administered questionnaire on adherence to
      HAART. At the same time, physicians estimated the current HAART adherence of
      their patient. MAIN OUTCOME MEASURE: Discordance between patient and physician on
      adherence to antiretroviral therapy. RESULTS: From May 1999 to March 2000, 320
      paired patient-physician assessments were obtained. Patients had a mean plasma
      HIV RNA of 315 copies/ml (64% had undetectable HIV RNA) and a mean CD4+ cell
      count of 577 cells x 10(6)/L. Nonadherence was reported by 30.9% of patients and
      estimated by physicians in 45.0% cases. In 111 cases (34.7%), patients and
      physicians were discordant on adherence to HAART. Kappa statistics was 0.27.
      Using patient-assessed adherence as reference, sensitivity, specificity, positive
      predictive value, and negative predictive value of physician-estimated adherence
      were 64.7%, 66.6%, 81.2%, and 45.8%, respectively. On multivariable analysis, low
      education level, unemployment, absence of a social worker in the clinical center,
      and unavailability of afternoon visits were significantly correlated with patient
      physician discordance on adherence to antiretrovirals. CONCLUSIONS: Physicians
      did not correctly estimate patient-reported adherence to HAART in more than one
      third of patients. Both social variables and factors related to the clinical
      center were important predictors of discordance between patients and physicians.
      Interventions to enhance adherence should include strategies addressed to improve
      patient-physician relationship.

PMID- 15566440
TI  - Gender differences in factors associated with adherence to antiretroviral
      therapy.
AB  - OBJECTIVE: To identify gender differences in social and behavioral factors
      associated with antiretroviral adherence. DESIGN: Prospective cohort study.
      SETTING: Methadone maintenance program. PARTICIPANTS: One hundred thirteen HIV
      seropositive current or former opioid users. MEASUREMENTS AND MAIN RESULTS:
      Participants were surveyed at baseline about social and behavioral
      characteristics and at monthly research visits about drug and alcohol use and
      medication side effects. Electronic monitors (MEMS) were used to measure
      antiretroviral adherence. Median adherence among women was 27% lower than among
      men (46% vs. 73%; P < .05). In gender-stratified multivariate models, factors
      associated with worse adherence in men included not belonging to an HIV support
      group (P < .0001), crack/cocaine use (P < .005), and medication side effects (P =
      .01). Among women, alcohol use (P = .005), heroin use (P < .05), and significant
      medication side effects (P < .005) were independently associated with worse
      adherence. In a model including both men and women, worse adherence was
      associated with lack of long-term housing (P < .005), not belonging to any HIV
      support groups (P < .0005), crack or cocaine use (P < .01), and medication side
      effects (P < .0005). In addition, worse adherence was associated with the
      interaction between female gender and alcohol use (P < or = .05). CONCLUSIONS: In
      this cohort of current and former opioid users, gender-stratified analysis
      demonstrated that different social and behavioral factors are associated with
      adherence in men and women. Among both men and women, worse adherence was
      associated with lack of long-term housing, not belonging to an HIV support group,
      crack/cocaine use, and medication side effects. Among women only, alcohol use was
      associated with worse adherence.

PMID- 15566441
TI  - Racial similarities and differences in predictors of mobility change over
      eighteen months.
AB  - OBJECTIVES: To define racial similarities and differences in mobility among
      community-dwelling older adults and to identify predictors of mobility change.
      DESIGN: Prospective, observational, cohort study. PARTICIPANTS: Nine hundred and
      five community-dwelling older adults. MEASURES: Baseline in-home assessments were
      conducted to assess life-space mobility, sociodemographic variables, disease
      status, geriatric syndromes, neuropsychological factors, and health behaviors.
      Disease reports were verified by review of medications, physician questionnaires,
      or hospital discharge summaries. Telephone interviews defined follow-up life
      space mobility at 18 months of follow-up. RESULTS: African Americans had lower
      baseline life-space (LS-C) than whites (mean 57.0 +/- standard deviation [SD]
      24.5 vs. 72.7 +/- SD 22.6; P < .001). This disparity in mobility was accompanied
      by significant racial differences in socioeconomic and health status. After 18
      months of follow-up, African Americans were less likely to show declines in LS-C
      than whites. Multivariate analyses showed racial differences in the relative
      importance and strength of the associations between predictors and LS-C change.
      Age and diabetes were significant predictors of LS-C decline for both African
      Americans and whites. Transportation difficulty, kidney disease, dementia, and
      Parkinson's disease were significant for African Americans, while low education,
      arthritis/gout, stroke, neuropathy, depression, and poor appetite were
      significant for whites. CONCLUSIONS: There are significant disparities in
      baseline mobility between older African Americans and whites, but declines were
      more likely in whites. Improving transportation access and diabetes care may be
      important targets for enhancing mobility and reducing racial disparities in
      mobility.

PMID- 15566442
TI  - Comparison of hospitalists and nonhospitalists in inpatient length of stay
      adjusting for patient and physician characteristics.
AB  - OBJECTIVE: To determine the independent effect of hospitalist status upon
      inpatient length of stay after controlling for case mix, as well as patient-level
      and provider-level variables such as age, years since physician medical school
      graduation, and volume status of provider. DESIGN: Observational retrospective
      cohort study employing a hierarchical random intercept logistic regression model.
      SETTING: Tertiary-care teaching hospital. PATIENTS: All admissions during 2001 to
      the department of medicine not sent initially to the medical intensive care unit
      or coronary care unit. MEASUREMENTS: Observed length of stay (LOS) compared to
      principle diagnosis related group (DRG)-specific mean LOS for hospitalist and
      nonhospitalist patients adjusting for patient age, gender, years since physician
      graduation from medical school, and physician volume status. MAIN RESULTS: The 9
      hospitalists discharged 2,027 patients while the nonhospitalists discharged 9,361
      patients. On average, hospitalist patients were younger, 63.3 versus 73.3 years
      (P < .0001). Hospitalists were more recently graduated from medical school, 13.8
      versus 22.5 years (P= .02). Each year of patient age was found to increase the
      likelihood of an above average LOS (odds ratio [OR], 1.01; 95% confidence
      interval [CI], 1.01 to 1.02; P < .001). In unadjusted analysis, hospitalists were
      less likely to have an above average LOS (OR, 0.51; 95% CI, 0.28 to 0.93; P=
      .03). Adjustment for effects of patient age and gender, physician gender, years
      since medical school graduation, and quintile of physician admission volume did
      not appreciably change the point estimate that hospitalist patients remained less
      likely to have above average LOS (OR, 0.60; 95% CI, 0.32 to 1.11; P= .11).
      CONCLUSIONS: For a given principle DRG, hospitalist patients were less likely to
      exceed the average LOS than were nonhospitalist patients. This effect was rather
      large, in that hospitalist status reduced the likelihood of above average LOS by
      about 49%. Adjustment for patient age, years since physician graduation, and
      admission volume did not significantly alter this finding. Further research
      should focus on identifying specific practices that account for hospitalism's
      effects.

PMID- 15566443
TI  - A survey of internal medicine residents and faculty about the duration of
      attendings' inpatient rotations.
AB  - OBJECTIVE: Some training programs are shortening the duration of attendings'
      rotations from 4 weeks to 2 weeks. Our objective was to determine the effect of 2
      week inpatient rotation on self-reported impact on medical education, patient
      care practices, and faculty performance by internal medicine residents and
      teaching faculty. DESIGN: Cross-sectional study using an anonymous mailed and
      emailed survey. SETTING: University-based internal medicine residency program in
      Buffalo, New York that recently introduced 2-week rotations. PARTICIPANTS: One
      hundred nineteen residents (99 responded, 83%) and 83 teaching faculty (76
      responded, 92%). MEASUREMENTS: Perceived impact on medical education, patient
      care, and attending performance on 7-point Likert scales ranging from negative (
      3) across neutral (0) to positive (+3) ratings. RESULTS: In general, residents
      and attendings felt that the short rotation negatively affects the attending's
      ability to evaluate residents and some aspects of patient care, but that it has
      no negative impact on residents' or medical students' learning. Attendings
      thought the 2-week rotation positively affects their private life and overall
      productivity. Subgroup analysis indicated that residents who graduated from U.S.
      medical schools were more pessimistic about the 2-week rotation compared to their
      international counterparts. Attendings who had completed at least one short
      rotation had consistently higher ratings of the 2-week rotation. CONCLUSION:
      Residents and attendings' perceptions suggest that the shorter attending
      inpatient rotation might have negative impact on medical education and patient
      care but positive effects on the attending's work productivity and private life.
      This tradeoff requires further evaluation including objective medical education
      and patient care outcomes.

PMID- 15566444
TI  - Prevalence and determinants of physician participation in conducting
      pharmaceutical-sponsored clinical trials and lectures.
AB  - BACKGROUND: The relationship between physicians and the pharmaceutical industry
      is controversial because of the potential for conflicts of interest. However,
      little empirical evidence exists on the extent of physician participation in
      activities sponsored by pharmaceutical companies. OBJECTIVES: To determine the
      prevalence of participation of internal medicine physicians in clinical trials
      and lectures sponsored by pharmaceutical companies and to describe factors that
      are associated with such participation. DESIGN, SETTING, AND PARTICIPANTS: We
      conducted a cross-sectional regional survey of 1,000 Maryland internal medicine
      physicians between February 2000 and January 2001 in order to measure the
      prevalence of physician participation in pharmaceutical-sponsored clinical trials
      and lectures. We also collected economic and demographic information to examine
      potential associations between physician characteristics and engagement in such
      activities. RESULTS: Of 835 eligible physicians 444 (53%) responded, of whom 37%
      reported engaging in pharmaceutical-sponsored clinical trials and/or lectures to
      supplement their incomes. In our multivariable analysis, subspecialists versus
      generalist physicians (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.14
      to 2.99), physicians in private group-single specialty and academic practice
      versus physicians in solo practice (OR, 2.30; 95% CI, 1.19 to 4.44 and OR, 2.56;
      95% CI, 1.17 to 5.61, respectively), and physicians with higher versus lower
      annual incomes (OR, 1.22; 95% CI, 1.04 to 1.44) had a greater odds of
      participation in these activities. Additionally, physicians dissatisfied with
      their income had a 140% greater odds of participation (OR, 2.36; 95% CI, 1.45 to
      3.83) than those who were satisfied with their income. CONCLUSIONS: A substantial
      number of internists engage in pharmaceutical industry-sponsored clinical trials
      and/or lectures in an effort to supplement their incomes. Physician
      dissatisfaction with income appears to partially explain such participation.

PMID- 15566445
TI  - Does racial concordance between HIV-positive patients and their physicians affect
      the time to receipt of protease inhibitors?
AB  - BACKGROUND: Compared to whites, African Americans have been found to have greater
      morbidity and mortality from HIV, partly due to their lower use of effective
      antiretroviral therapy. Why racial disparities in antiretroviral use exist is not
      completely understood. We examined whether racial concordance (patients and
      providers having the same race) affects the time of receipt of protease
      inhibitors. METHODS: We analyzed data from a prospective, cohort study of a
      national probability sample of 1,241 adults receiving HIV care with linked data
      from 287 providers. We examined the association between patient-provider racial
      concordance and time from when the Food and Drug Administration approved the
      first protease inhibitor to the time when patients first received a protease
      inhibitor. RESULTS: In our unadjusted model, white patients received protease
      inhibitors much earlier than African-American patients (median 277 days compared
      to 439 days; P < .0001). Adjusting for patient characteristics only, African
      American patients with white providers received protease inhibitors significantly
      later than African-American patients with African-American providers (median 461
      days vs. 342 days respectively; P < .001) and white patients with white providers
      (median 461 vs. 353 days respectively; P= .002). In this model, no difference was
      found between African-American patients with African-American providers and white
      patients with white providers (342 vs. 353 days respectively; P > .20). Adjusting
      for patients' trust in providers, as well as other patient and provider
      characteristics in subsequent models, did not account for these differences.
      CONCLUSION: Patient-provider racial concordance was associated with time to
      receipt of protease inhibitor therapy for persons with HIV. Racial concordance
      should be addressed in programs, policies, and future racial and ethnic health
      disparity research.

PMID- 15566446
TI  - Why do providers contribute to disparities and what can be done about it?
AB  - This paper applies social cognition research to understanding and ameliorating
      the provider contribution to racial/ethnic disparities in health care. We discuss
      how fundamental cognitive mechanisms such as automatic, unconscious processes
      (e.g., stereotyping) can help explain provider bias. Even well-intentioned
      providers who are motivated to be nonprejudiced may stereotype racial/ethnic
      minority members, particularly under conditions of that diminish cognitive
      capacity. These conditions-time pressure, fatigue, and information overload-are
      frequently found in health care settings. We conclude with implications of the
      social-cognitive perspective for developing interventions to reduce provider
      bias.

PMID- 15566452
TI  - Relationship-centered care and the patient-physician relationship.

PMID- 15566453
TI  - Role of uterine artery velocimetry using color-flow Doppler and electromyography
      of uterus in prediction of preterm labor.
AB  - AIM: To evaluate the role of Doppler waveforms of uterine vessels and
      electromyography (EMG) of the uterus in predicting preterm labor. METHODS: One
      hundred ante-natal women at >or=24 weeks of gestation who fulfilled the selection
      criteria were included in the study. A single Doppler recording for bilateral
      uterine vessels was taken at >or=26 weeks gestation using the transvaginal route.
      Transabdominal EMG of the uterus was recorded serially at 4-week intervals from
      24 weeks until delivery or until 37 weeks were completed. RESULTS: Women with a
      sensation of heaviness in the lower abdomen during pregnancy had a significant
      association with preterm delivery. Of the three Doppler indices, the
      systolic/diastolic ratio and the resistivity index of uterine vessels were found
      to have a sensitivity as high as 83-95% for the prediction of preterm labor. The
      electrical activity of uterine musculature, as recorded using EMG, showed that
      there was a statistically significant difference between the electrical activity
      recorded for the two groups at 31 weeks and later, while the duration of burst
      activity was significantly longer in the preterm group at 26 weeks and later.
      CONCLUSIONS: Patients with a dull aching sensation in the lower abdomen should
      not be neglected. Doppler of the uterine vessels and EMG of the uterus could
      prove to be a good predictor of preterm labor.

PMID- 15566454
TI  - Daily versus intermittent iron supplementation in pregnant women: hematological
      and pregnancy outcome.
AB  - AIM: To compare the hematological parameters and pregnancy outcome in women
      receiving daily versus weekly iron supplements during pregnancy. METHODS: A
      prospective randomized controlled study was carried out at the Department of
      Obstetrics and Gynaecology of the All India Institute of Medical Sciences, New
      Delhi, India, during which 111 women were randomized to receive either 100 mg
      elemental iron daily (n=55) or 200 mg elemental iron weekly (n=56). Hemogram and
      serum ferritin level estimation were carried out at the beginning of pregnancy
      and within the 32-34-week period of gestation. Side-effects, compliance and the
      number of tablets consumed were noted for each group. The mean birth weight,
      period of gestation at delivery and mode of delivery were also compared between
      the two intervention groups. RESULTS: There was no significant difference in the
      mean hemoglobin levels between the two intervention groups at the end of an
      average 17 weeks of iron supplementation. However, among anemic women who
      received daily supplementation, there was a greater rise in hemoglobin compared
      with those receiving supplementation weekly. The serum ferritin level was lower
      in the weekly supplemented group compared with that in the daily. There was no
      difference in the mean birth weight, period of gestation and mode of delivery
      between the two groups. Side-effects and non-compliance were significantly higher
      (P<0.001) in the daily supplemented group. CONCLUSIONS: Weekly iron
      supplementation is an effective option for prophylaxis in non-anemic pregnant
      women, but has less than optimal benefit in anemic women.

PMID- 15566455
TI  - Diagnostic performance of quantitative ultrasound calcaneus measurement in case
      finding for osteoporosis in Thai postmenopausal women.
AB  - AIM: Dual-energy X-ray absorptiometry (DXA) is currently considered the gold
      standard for the diagnosis of osteoporosis. Quantitative ultrasound (QUS) can be
      an alternative method that is less expensive, portable, and can be used at a
      primary care level to indicate osteoporosis in women. The present study aimed to
      assess the diagnostic performance of QUS calcaneus measurement in a case finding
      for osteoporosis in Thai postmenopausal women using DXA as a gold standard.
      METHODS: Three hundred postmenopausal women, who had not menstruated normally for
      at least 1 year, were included in the study. To determine the accuracy and
      reliability of QUS of the calcaneus, calcaneus bone density measurement was
      carried out using the QUS and left femoral neck bone density was measured using
      DXA. Bone mass density (BMD) was interpreted as osteoporotic or normal using WHO
      criteria for determining the performance of QUS. Optimal cut-off values were
      determined using a receiver operating characteristic (ROC) curve for diagnosing
      the osteoporosis cases. RESULTS: The number of osteoporosis cases in this study
      was 107 (35.67%). The sensitivity, specificity, positive and negative predictive
      values were 39.25%, 91.71%, 72.41%, 73.14%, respectively, when using the T-score
      of the WHO criteria as a reference. The positive and negative likelihood ratios
      were 4.73 and 0.66. When using the ROC curve to determine the optimal cut-off
      values, using the stiffness index of the QUS and categorizing age (<65 years and
      >or=65 years) before conducting the test, sensitivity and specificity were 77.6%
      and 59.6%, respectively. CONCLUSIONS: Bone mass density measurement for
      predicting osteoporosis using QUS had a very low sensitivity and was not good
      enough to replace the standard tool (DXA).

PMID- 15566456
TI  - Use of heparin to lower the incidence of phlebitis induced by anti-neoplastic
      agents used in ovarian cancer.
AB  - AIM: To investigate whether heparin infusion with the administration of anti
      neoplastic agents in ovarian cancer can reduce the occurrence of phlebitis as a
      complication of chemotherapy. METHODS: The subjects were 20 patients with ovarian
      cancer who developed phlebitis following their first course of anti-cancer
      chemotherapy. In the subsequent chemotherapy course, 10 patients received heparin
      infusion of 5000 U, starting 3 h before the administration of anti-neoplastic
      agents and continuing concomitantly with the agents for 12 h. The other 10
      patients (control) were treated with anti-neoplastic agents alone. RESULTS: Only
      one (10%) of 10 patients who had received heparin developed phlebitis, while
      eight patients (80%) in the control group did (P=0.005). In the heparin group,
      there were no toxic effects of heparin observed. The prothrombin time, activated
      partial thromboplastin time, fibrinogen, and platelet count did not differ before
      and after the completion of chemotherapy. CONCLUSION: Concurrent infusion of
      heparin and anti-neoplastic agents in ovarian cancer is a safe and effective
      method of preventing phlebitis induced by chemotherapy.

PMID- 15566457
TI  - Urological injuries during hysterectomies: a 6-year review.
AB  - AIM: Urological injuries that occur during hysterectomy are a rare but important
      cause of morbidity. An understanding of the risk factors can help us to reduce
      their incidence and studying their management and outcome could help us to evolve
      optimal management strategies. The aim of the present study was to examine the
      incidence of urological injuries that occur during hysterectomy and to determine
      the risk factors, management and outcome of such injuries. METHODS: A
      retrospective analysis of cases of urological injuries sustained during
      hysterectomies carried out from June 1996 until May 2002, at our institution. The
      chi-squared test was applied for statistical analysis. RESULTS: The overall
      incidence of urological injuries was 0.40% (0.28% bladder and 0.12% ureteral). No
      ureteral injuries occurred during vaginal surgery. The incidence of bladder
      injury was significantly higher in non-descent vaginal hysterectomies compared
      with abdominal hysterectomies or vaginal hysterectomies for genital prolapse
      (P<0.05). Hysterectomy for ovarian malignancies had a significantly higher risk
      for bladder injuries compared with other indications. Bladder injuries detected
      during vaginal hysterectomies could be managed through the vaginal route. All the
      repairs healed successfully. CONCLUSIONS: Non-descent vaginal hysterectomy and
      hysterectomy for ovarian malignancies have a higher risk of bladder injury.
      Urological injuries during hysterectomy are uncommon. Early detection and
      appropriate management ensure successful healing and minimal long-term sequelae.

PMID- 15566458
TI  - Long-term serological outcome of infants who received frozen-thawed milk from
      human T-lymphotropic virus type-I positive mothers.
AB  - AIM: Human T-lymphotropic virus type-I (HTLV-I) infection occurs via mothers'
      milk during feeding. However, freeze-thaw processing can eliminate the
      infectivity of the mother's milk of HTLV-I carriers. METHODS: A long-term follow
      up survey was conducted to investigate the HTLV-I infectivity of frozen-thawed
      mothers' milk among infants whose mothers were HTLV-I seropositive. RESULTS:
      Infants fed frozen-thawed mothers' milk did not become HTLV-I antibody-positive
      up until 1 year old, and all children followed up until an age of 11-12 years
      were antibody negative. CONCLUSIONS: This study showed that freeze-thaw
      processing can eliminate the HTLV-I infectivity of mothers' milk, and that HTLV-I
      carriers can indirectly feed their infants using frozen-thawed mothers' milk as a
      way to prevent HTLV-I infection.

PMID- 15566459
TI  - Inhibin-producing ovarian granulosa cell tumor as a cause of secondary
      amenorrhea: case report and review of the literature.
AB  - We report the case of 31-year-old patient with an inhibin B-secreting granulosa
      cell tumor of the left ovary who presented with secondary amenorrhea.
      Preoperative serum hormonal levels were as follows: follicle-stimulating hormone
      (FSH) 0.3 mIU/mL, luteinizing hormone (LH) 9.81 mIU/mL, estradiol 142.0 pg/mL and
      inhibin B 2429 pg/mL. Gonadotropin-releasing hormone (GnRH) test revealed no FSH
      response and a normal LH response. After removal of the tumor, the levels of FSH
      and inhibin B returned to within the normal range, and regular menses resumed 27
      days postoperatively. In premenopausal women, secondary amenorrhea may be the
      initial manifestation of granulosa cell tumor. A low FSH level coupled with
      normal levels of E2 and LH, the inhibition of the FSH response to GnRH and an
      elevated inhibin level suggest the presence of an inhibin-secreting ovarian tumor
      and also rule out the possibility of isolated FSH deficiency.

PMID- 15566460
TI  - Large pseudocyst of the umbilical cord associated with patent urachus.
AB  - Cystic masses of the umbilical cord have been detected in the second and third
      trimesters of pregnancy in association with fetal abdominal wall defects and
      chromosomal anomalies. We present a case of an umbilical cord pseudocyst
      diagnosed using routine ultrasound at the 20 weeks of gestation. Serial
      sonography followed the progression of the cystic masses. A 2960-g male infant
      was delivered at term, in whom a patent urachus was detected. The infant
      underwent repair with closure of the patent urachus and plastic reconstruction of
      the abdominal wall, and the postoperative course was uneventful. This case
      demonstrated an uneventful outcome despite the persistent multiple cord cysts.

PMID- 15566461
TI  - Relationship between the timing of hysterosalpingography before gamete
      intrafallopian transfer and the subsequent fertility outcome.
AB  - AIM: To investigate the prognostic significance of hysterosalpingography carried
      out before one-sided gamete intrafallopian transfer for unexplained infertility.
      METHODS: Fifty-nine first gamete intrafallopian transfer cycles in 59 couples
      with unexplained infertility were evaluated in two groups: 30 women with a
      hysterosalpingogram carried out 1-6 months prior to gamete intrafallopian
      transfer procedure combined with diagnostic laparoscopy, and 29 women with a
      hysterosalpingogram carried out during any other interval up to 2 years. The
      outcome measures were biochemical pregnancy, clinical pregnancy, miscarriage,
      preterm delivery, and term delivery. Groups were compared using Student's t-test
      and chi-squared tests. Logistic regression was used to predict the effects of
      hysterosalpingography on subsequent fertility outcomes. RESULTS: Univariate
      analysis yielded no significant differences across groups regarding the baseline
      characteristics and outcome measures. When confounding factors were controlled,
      carrying out hysterosalpingography at some time before 6 months of gamete
      intrafallopian transfer was associated with 5.2- and 3.4-fold increased clinical
      pregnancy and term delivery rates, respectively. CONCLUSIONS: An additional
      hysterosalpingography at most 6 months prior to gamete intrafallopian transfer
      procedure might improve fertility prospects. This effect could be attributed to
      proper selection of the fallopian tube for cannulation during transfer or some
      therapeutic effect of hysterosalpingography.

PMID- 15566462
TI  - Retroperitoneal schwannoma bearing at the right vaginal wall.
AB  - Benign schwannoma commonly arises from schwann cells of the neural sheath. We
      report a rare case of retroperitoneal schwannoma bearing at the vaginal wall. The
      tumor was a 7x5x4-cm solid mass revealed using several image techniques and
      diagnosed to be a retroperitoneal tumor preoperatively. The tumor was tightly
      attached to the vaginal submucosal tissue, so complete surgical resection was
      difficult. However, an almost complete resection was carried out macroscopically
      using laparotomy. Histologic and immunohistochemical studies confirmed the
      diagnosis. The patient has been followed for 18 months after the operation, but
      there is no evidence of recurrent tumor.

PMID- 15566463
TI  - Cloning and characterization of myogenic regulatory genes in three Ictalurid
      species.
AB  - We report sequence, tissue expression and map-position data for myogenin, MYOD1,
      myostatin and follistatin in three Ictalurid catfish species: channel catfish
      (Ictalurus punctatus), blue catfish (I. furcatus) and white catfish (Ameiurus
      catus). These genes are involved in muscle growth and development in mammals and
      may play similar roles in catfish. Amino acid sequences were highly conserved
      among the three Ictalurid species (>95% identity), moderately conserved among
      catfish and zebrafish (approximately 80% identity), and less conserved among
      catfish and humans (approximately 40-60% identity) for all four genes. Gene
      structure (number of exons and introns and exon-intron boundaries) was conserved
      between catfish and other species for all genes. Myogenin and MYOD1 expression
      was limited to skeletal muscle in juvenile channel catfish, similar to expression
      patterns for these genes in other fish and mammalian species. Myostatin was
      expressed in a variety of tissues in juvenile channel catfish, a pattern common
      in other fish species but contrasting with data from mammals where myostatin is
      primarily expressed in skeletal muscle. Follistatin was expressed in juvenile
      catfish heart, testes and spleen. All four genes contained polymorphic
      microsatellite repeats in non-coding regions and linkage analysis based on
      inheritance of these microsatellite loci was used to place the genes on the
      channel catfish linkage map. Information provided in this study will be useful in
      further studies to determine the role these genes play in muscle growth and
      development in catfish.

PMID- 15566464
TI  - Bovine umbilical hernia maps to the centromeric end of Bos taurus autosome 8.
AB  - Twelve bull calves were produced by mating elite Israeli cows to "Glenhapton
      Enhancer", a Canadian Holstein bull. The frequency of umbilical hernia (UH) in
      the progeny of the sons ranged from 1 to 21%, consistent with the hypothesis that
      Enhancer is the carrier of major dominant or codominant gene with partial
      penetrance for UH. Five sons of Enhancer produced progeny with >10% frequency of
      UH including sire 3259, whereas progeny of three sons had <3% UH. A total of 116
      grand-progeny of Enhancer, all progeny of 3259, were genotyped for 59
      microsatellites spanning the 29 bovine autosomes. Of these offspring, 41 were
      affected. Significant differences in paternal allele frequencies between the
      affected and unaffected progeny groups were found for marker BMS1591 on bovine
      chromosome 8 (BTA8). The UH-associated paternal allele originated from Enhancer.
      The chromosomal segment associated with UH was more precisely mapped between
      UWCA47, on the centromeric end of BTA8 and RM321, 12 cM from the centromere. A
      maximum LOD score of 3.84 was obtained 2.5 cM from the centromere with a support
      interval of 8 cM. Haplotype analysis of eight sons of Enhancer suggested that the
      UH gene is located in the centromeric end of BTA8 beyond ARO71/ARO72. Thus, by
      integrating the results from progeny of sire 3259 and sons of Enhancer the
      location of the UH gene was further refined to the BTA8 segment between
      ARO71/ARO72 and UWCA47.

PMID- 15566465
TI  - Mapping of the bovine genes of the de novo AMP synthesis pathway.
AB  - Summary The purine nucleotides adenosine monophosphate (AMP) and guanosine
      monophosphate (GMP) are critical for energy metabolism, cell signalling and cell
      reproduction. Despite their essential function, little is known about the
      regulation and in vivo expression pattern of the genes involved in the de novo
      purine synthesis pathway. The complete coding region of the bovine
      phosphoribosylaminoimidazole carboxylase gene (PAICS), which catalyses steps 6
      and 7 of the de novo purine biosynthesis pathway, as well as bovine genomic
      sequences of the six other genes in the pathway producing inosine monophosphate
      (IMP) and AMP [phosphoribosyl pyrophosphate amidotransferase (PPAT),
      phosphoribosylglycinamide formyltransferase (GART),
      phosphoribosylformylglycinamidine synthase (PFAS), adenylosuccinate lyase (ADSL),
      5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP
      cyclohydrolase (ATIC) and adenylosuccinate synthase (ADSS)], were identified. The
      genes were mapped to segments of six different bovine chromosomes using a
      radiation hybrid (RH) cell panel. The gene PPAT, coding for the presumed rate
      limiting enzyme of the purine de novo pathway was closely linked to PAICS on
      BTA6. These, and the other bovine locations i.e. GART at BTA1, PFAS at BTA19,
      ADSL at BTA5, ATIC at BTA2 and ADSS at BTA16, are in agreement with published
      comparative maps of cattle and man. PAICS and PPAT genes are known to be closely
      linked in human, rat and chicken. Previously, an expressed sequence fragment of
      PAICS (Bos taurus corpus luteum, BTCL9) was mapped to BTA13. By isolation and
      characterization of a BAC clone, we have now identified a PAICS processed
      pseudogene sequence (psiPAICS) on BTA13. Processed pseudogene sequences of PAICS
      and other genes of the purine biosynthesis pathway were identified in several
      mammalian species, indicating that the genes of this pathway have been
      susceptible to retrotransposition. The seven bovine genes are expressed at a
      higher level in testicular and ovary tissues compared with skeletal muscle.

PMID- 15566466
TI  - Comparative analysis and development of microsatellite markers on swine (Sus
      scrofa) chromosome 1qter.
AB  - Several quantitative trait loci (QTL) have been detected on SSC1qter (Sus scrofa
      chromosome 1qter), including QTL for the number of vertebrae, as reported in our
      previous study. To provide the tools for analysis of QTLs on SSC1qter, we
      constructed a comparative map of swine and human. In addition, we identified 26
      swine STSs and mapped 16 of them on SSC1qter using the INRA - University of
      Minnesota porcine radiation hybrid (IMpRH) panel. We screened a BAC library using
      these swine STSs and developed 35 new polymorphic microsatellite markers from the
      BAC clones, of which 26 were informative in our reference family. We also mapped
      nine microsatellite markers we had isolated previously. Consequently a total of
      44 new polymorphic microsatellite markers were located within a 60-cM region of
      SSC1qter, spanning from SW1092 to the telomere.

PMID- 15566467
TI  - Quantitative trait loci for male reproductive traits in beef cattle.
AB  - The objective of the present study was to detect quantitative trait loci (QTL)
      for male reproductive traits in a half-sib family from a Bos indicus (Brahman) x
      Bos taurus (Hereford) sire. The sire was mated with MARC III (1/4 Hereford, 1/4
      Angus, 1/4 Red Poll and 1/4 Pinzgauer) cows. Testicular traits were measured from
      126 male offspring born in 1996 and castrated at 8.5 months. Traits analysed were
      concentration of follicle stimulating hormone in peripheral blood at castration
      (FSH), paired testicular weight (PTW) and paired testicular volume (PTV) adjusted
      for age of dam, calculated age at puberty (AGE), and body weight at castration
      (BYW). A putative QTL was observed for FSH on chromosome 5. The maximum F
      statistic was detected at 70 cM from the beginning of the linkage group. Animals
      inheriting the Hereford allele had a 2.47-ng/ml higher concentration of FSH than
      those inheriting the Brahman allele. Evidence also suggests the existence of a
      putative QTL on chromosome 29 for PTW, PTV, AGE and BYW. The maximum F-statistic
      was detected at cM 44 from the beginning of the linkage group for PTW, PTV and
      AGE, and at cM 52 for BYW. Animals that inherited the Brahman allele at this
      chromosomal region had a 45-g heavier PTW, a 42-cm(3) greater PTV, a 39-day
      younger AGE and a 22.8-kg heavier BYW, compared with those inheriting the
      Hereford allele. This is the first report of QTL for male reproductive traits in
      cattle.

PMID- 15566468
TI  - Identification of a mutation associated with factor XI deficiency in Holstein
      cattle.
AB  - An autosomal recessive deficiency of blood coagulation factor XI (FXI) has been
      described in Holstein cattle. Current testing methods are unsuitable for
      accurately identifying carriers (heterozygotes) of the disease. To identify the
      molecular basis of this deficiency, a polymerase chain reaction (PCR)-based
      strategy was implemented to clone and sequence the bovine FXI gene (F11) from
      animals of different genotypes. Approximately 14 kb of genomic DNA sequence and
      1.8 kb of cDNA sequence, corresponding to exon 3 through the 3'-UTR, of the
      bovine gene were obtained. Comparison of sequences derived from homozygous normal
      and deficient individuals revealed that FXI deficiency in Holsteins is associated
      with the insertion of a 76 bp segment [AT(A)(28)TAAAG(A)(26)GGAAATAATAATTCA]
      within exon 12. This insertion introduces a stop codon that results in a mature
      FXI protein lacking the functional protease domain encoded by exons 13, 14 and
      15. Based on these data, a DNA-based diagnostic test has been developed for
      accurate genotyping. Using this method, the frequency of the mutated allele has
      been determined to be 1.2% in a contemporary population of the USA Holstein
      sires.

PMID- 15566469
TI  - PRNP polymorphisms in Chinese ovine, caprine and bovine breeds.
AB  - Transmissible spongiform encephalopathy (TSE) is a neurodegenerative disorder in
      humans and animals. Polymorphisms and mutations in the prion protein (PRNP) gene
      have been associated with the incidence of natural and experimental TSE and the
      incubation period length. In this study, we determined PRNP polymorphisms in
      Chinese ovine, caprine and bovine breeds using 400 samples from 13 ovine and
      caprine breeds and 250 samples from nine bovine breeds. In the ovine and caprine
      PRNP gene, we found five previously unreported amino acid polymorphisms and two
      silent nucleotide alterations. In bovine PRNP, we found eight previously
      unreported amino acid polymorphisms and six silent nucleotide alterations.

PMID- 15566470
TI  - Molecular cloning and analysis of the swamp and river buffalo leptin gene.

PMID- 15566471
TI  - Development of type I markers in channel catfish through intron sequencing.

PMID- 15566472
TI  - Exclusion of WT1 as a candidate gene for canine SRY-negative XX sex reversal.

PMID- 15566473
TI  - Linkage mapping of the MC3R gene to porcine chromosome 17.

PMID- 15566474
TI  - Detection of SNPs and linkage and radiation hybrid mapping of the porcine C
      reactive protein (CRP ) gene.

PMID- 15566475
TI  - Comparison of avian myostatin genes.

PMID- 15566476
TI  - Radiation hybrid mapping of four genes (MYBPC1, LUM, ZRF1 and ATP2B4) expressed
      in embryo skeleton muscle to pig chromosomes 5 and 9.

PMID- 15566477
TI  - Addition of 14 anchored loci to the porcine chromosome 8 comparative map.

PMID- 15566478
TI  - Physical mapping of the KCNJ8 gene to bovine chromosome 5q3.2-q3.4.

PMID- 15566479
TI  - Assignment of the PRPH gene to bovine chromosome 5q1.4 by FISH and confirmation
      by RH mapping.

PMID- 15566480
TI  - Mapping of CYP11B and a putative CYHR1 paralogous gene to bovine chromosome 14 by
      FISH.

PMID- 15566481
TI  - Ten polymorphic microsatellite markers from Arctic charr (Salvelinus alpinus):
      linkage analysis and amplification in other salmonids.

PMID- 15566482
TI  - Thirty-five new equine microsatellite loci assigned to genetic linkage and
      radiation hybrid maps.

PMID- 15566483
TI  - Sixty-seven new equine microsatellite loci assigned to the equine radiation
      hybrid map.

PMID- 15566484
TI  - Isolation, characterization and chromosome assignment of 341 newly isolated
      equine TKY microsatellite markers.

PMID- 15566485
TI  - The FAS-activated serine/threonine kinase gene maps to canine chromosome 16.

PMID- 15566486
TI  - Mapping of the bovine homologue of the human chromosome 14 open reading frame 4
      (C14orf4) gene to BTA10q36.

PMID- 15566487
TI  - Mapping of the ATP11B gene and refined localization of the SOX2 and FXR1 genes to
      BTA1q33.

PMID- 15566488
TI  - The porcine homologues of six genes located on human chromosome 8 (RAB2, CA3,
      PTDSS1, MATN2, FZD6 and SQLE) assigned to porcine chromosome 4 by fluorescence in
      situ hybridization.

PMID- 15566489
TI  - Genetic testing for feline polycystic kidney disease.

PMID- 15566490
TI  - Nanometre localization of single ReAsH molecules.
AB  - ReAsH is a red-emitting dye that binds to the unique sequence Cys-Cys-Xaa-Xaa-Cys
      Cys (where Xaa is a noncysteine amino acid) in the protein. We attached a single
      ReAsH to a calmodulin with an inserted tetracysteine motif and immobilized
      individual calmodulins to a glass surface at low density. Total internal
      reflection fluorescence microscopy was used to image individual ReAsH molecules.
      We determined the centre of the distribution of photons in the image of a single
      molecule in order to determine the position of the dye within 5 nm precision and
      with an image integration time of 0.5 s. The photostability of ReAsH was also
      characterized and observation times ranging from several seconds to over a minute
      were observed. We found that 2-mercaptoethanesulphonic acid increased the number
      of collected photons from ReAsH molecules by a factor of two. Individual ReAsH
      molecules were then moved via a nanometric stage in 25 or 40 nm steps, either at
      a constant rate or at a Poisson-distributed rate. Individual steps were clearly
      seen, indicating that the observation of translational motion on this scale,
      which is relevant for many biomolecular motors, is possible with ReAsH.

PMID- 15566491
TI  - Three-dimensional representation of curved nanowires.
AB  - Nanostructures, such as nanowires, nanotubes and nanocoils, can be described in
      many cases as quasi one-dimensional curved objects projecting in three
      dimensional space. A parallax method to construct the correct three-dimensional
      geometry of such one-dimensional nanostructures is presented. A series of
      scanning electron microscope images was acquired at different view angles, thus
      providing a set of image pairs that were used to generate three-dimensional
      representations using a matlab program. An error analysis as a function of the
      view angle between the two images is presented and discussed. As an example
      application, the importance of knowing the true three-dimensional shape of boron
      nanowires is demonstrated; without the nanowire's correct length and diameter,
      mechanical resonance data cannot provide an accurate estimate of Young's modulus.

PMID- 15566492
TI  - Multiple imaging techniques demonstrate the manipulation of surfaces to reduce
      bacterial contamination and corrosion.
AB  - Surface imaging techniques were combined to determine appropriate manipulation of
      technologically important surfaces for commercial applications. The
      complementarity of the microscopy methods, scanning electron microscopy, electron
      probe microanalysis and atomic force microscopy assessed and correlated form and
      function of the surface modifications. Stainless steel disks (1 cm in diameter)
      were laser-cut from the same sheets of stainless steel and treated by
      electropolishing or left untreated for controls. Each treatment was analysed
      separately using each technique. First, the disks were examined by visual
      inspection and electron probe microanalysis for surface characteristics and
      elemental composition, respectively. Aliquots of bacterial suspensions (saline
      rinses of poultry carcasses from a commercial broiler processing plant) were then
      diluted in broth and monitored for growth by spectrophotometry. Stainless steel
      disks (1 cm in diameter) were added and the cultures were grown to sufficient
      density to allow attachment of bacterial cells to test surfaces. Relative
      differences in the surface morphology shown by atomic force microscopy, including
      Z ranges, roughness and other measurements, corresponded by treatment with the
      differences in reduction of bacterial counts shown by scanning electron
      microscopy. A model of wet-processing conditions tested the effects of corrosive
      treatment of surfaces. Less bacterial attachment occurred after corrosive
      treatment on controls and electropolished samples. Electropolishing significantly
      reduced bacterial numbers and the effects of corrosive action compared to the
      controls. Thus, the multiple imaging techniques showed that engineered changes on
      stainless steel surfaces improved the resistance of the surface finish to
      bacterial attachment, biofilm formation, and corrosive action.

PMID- 15566493
TI  - Microinfrared reflection spectroscopic mapping: application to the detection of
      hydrogen-related species in natural quartz.
AB  - A new method of microinfrared reflection spectroscopy and mapping analysis is
      briefly introduced. It was used to detect distributions and structures of
      hydrogen-related species (e.g. H(2)O, SiOH and SiH) in plastically deformed
      natural quartz. We used a Fourier transform-infrared spectrometer with a
      microscopic imaging system fully automated for all microscope functions (e.g.
      focusing, aperture, stage motion and measurements). Mapping can be made in thin
      sections with a thickness of 50 microm at room temperature and low temperatures
      (77 K) using a liquid N(2) cooling system. Infrared reflection spectra were
      obtained by five scans for each point with a range from 4000 to 400 cm(-1). The
      spectra were measured five times within about 2.5 s at each position. The
      scanning interval was 100-150 microm using a 100 x 100 microm(2) aperture. All
      obtained spectral data were stored in computer memory to construct two
      dimensional mappings of infrared absorption. From the comparisons between
      infrared mapping images and deformation microstructures, in addition to the
      molecular H(2)O around 3600-3400 cm(-1), the hydrogen-related point defects (i.e.
      SiOH and SiH) around 970-900 cm(-1) within quartz grains and between grain
      boundaries increased with decreasing grain sizes (increasing plastic strain). The
      method can detect the SiOH and SiH along grain boundaries that enhance the
      hydrolytic weakening of natural quartz.

PMID- 15566494
TI  - Shear force near-field optical microscope based on Q-controlled bimorph sensor
      for biological imaging in liquid.
AB  - Shear force near-field microscopy on biological samples in their physiological
      environment loses considerable sensitivity and resolution as a result of liquid
      viscous damping. Using a bimorph-based cantilever sensor incorporating force
      feedback, as recently developed by us, gives an alternative force detection
      scheme for biological imaging in liquid. The dynamics and sensitivity of this
      sensor were theoretically and experimentally discussed. Driving the bimorph
      cantilever close to its resonance frequency with appropriate force feedback
      allows us to obtain a quality factor (Q-factor) of up to 10(3) in water, without
      changing its intrinsic resonance frequency and spring constant. Thus, the force
      detection sensitivity is improved. Shear force imaging on mouse brain sections
      and human skin tissues in liquid with an enhanced Q-factor of 410 have shown a
      high sensitivity and stability. A resolution of about 50 nm has been obtained.
      The experimental results suggest that the system is reliable and particularly
      suitable for biological cell imaging in a liquid environment.

PMID- 15566495
TI  - Application of Fourier transform and autocorrelation to cluster identification in
      the three-dimensional atom probe.
AB  - Because of the increasing number of collected atoms (up to millions) in the three
      dimensional atom probe, derivation of chemical or structural information from the
      direct observation of three-dimensional images is becoming more and more
      difficult. New data analysis tools are thus required. Application of a discrete
      Fourier transform algorithm to three-dimensional atom probe datasets provides
      information that is not easily accessible in real space. Derivation of mean
      particle size from Fourier intensities or from three-dimensional autocorrelation
      is an example. These powerful methods can be used to detect and image nano
      segregations. Using three-dimensional 'bright-field' imaging, single nano
      segregations were isolated from the surrounding matrix of an iron-copper alloy.
      Measurement of the inner concentration within clusters is, therefore,
      straightforward. Theoretical aspects related to filtering in reciprocal space are
      developed.

PMID- 15566496
TI  - Investigation of quantitative secondary electron imaging of semiconducting
      polymer materials using environmental scanning electron microscopy.
AB  - The development of environmental scanning electron microscopy has opened the way
      for the examination of a wide variety of new sample types that were previously
      inaccessible to conventional scanning electron microscope techniques. With the
      advent of such a new methodology comes also the potential for new contrast
      mechanisms. We investigated the use of environmental scanning electron microscopy
      on semiconducting organic polymer materials. We observed contrast from these
      materials in secondary electron images, this contrast being attributed to
      differences in electron yield due to the polymer's electronic structure. Further
      study of these materials, and specifically the influence of film thickness on
      signal, has indicated a significant effect as the secondary electrons move
      through the sample. Systematic studies such as these are needed for a full
      understanding of the relationship between electronic properties and signal and,
      hence, the ability to probe structure-property relationships in greater depth.

PMID- 15566497
TI  - An optical-axis freezing stage for laser-scanning microscopy of broad ice-water
      interfaces.
AB  - This article presents a method to view a dynamic ice interface along the axis of
      ice growth using a laser-scanning microscope. A deep liquid volume is chilled
      from below so that ice growth is directed upward toward the microscope objective.
      The interface is made visible by rejection of fluorescent dye from the solid
      phase into the liquid. Images of the interface morphology in water with solutes
      of interest to cryobiology illustrate the imaging capability. These images are
      processed to quantify the lamellar structure of the ice interface. The optical
      axis cryostage provides advantages over horizontal arrangements because (1)
      immersion objectives enhance, rather than disturb, the desired thermal gradient,
      and (2) features in the ice interface are not confined within a narrow capillary
      tube or microscope slide. This arrangement loses some of the thermal control
      found in planar freezing stages, and the dynamic, refractive interface presents
      challenges to confocal microscopy.

PMID- 15566498
TI  - A method for determining void arrangements in inverse opals.
AB  - The periodic arrangement of voids in ceramic materials templated by colloidal
      crystal arrays (inverse opals) has been analysed by transmission electron
      microscopy. Individual particles consisting of an approximately spherical array
      of at least 100 voids were tilted through 90 degrees along a single axis within
      the transmission electron microscope. The bright-field images of these particles
      at high-symmetry points, their diffractograms calculated by fast Fourier
      transforms, and the transmission electron microscope goniometer angles were
      compared with model face-centred cubic, body-centred cubic, hexagonal close
      packed, and simple cubic lattices in real and reciprocal space. The spatial
      periodicities were calculated for two-dimensional projections. The systematic
      absences in these diffractograms differed from those found in diffraction
      patterns from three-dimensional objects. The experimental data matched only the
      model face-centred cubic lattice, so it was concluded that the packing of the
      voids (and, thus, the polymer spheres that composed the original colloidal
      crystals) was face-centred cubic. In face-centred cubic structures, the stacking
      fault displacement vector is a/6<211> . No stacking faults were observed when
      viewing the inverse opal structure along the orthogonal <110>-type directions,
      eliminating the possibility of a random hexagonally close-packed structure for
      the particles observed. This technique complements synchrotron X-ray scattering
      work on colloidal crystals by allowing both real-space and reciprocal-space
      analysis to be carried out on a smaller cross-sectional area.

PMID- 15566499
TI  - A primer on the molecular virology of hepatitis C.
AB  - Exciting advances have recently been made in the understanding of the molecular
      virology of hepatitis C. Powerful model systems have been developed that allow to
      systematically dissect important steps of the hepatitis C virus (HCV) life cycle.
      These include new systems for functional analyses of the HCV glycoproteins,
      providing insights into possible HCV receptors and cell entry mechanisms, and the
      replicon system, which has revolutionized investigation of HCV RNA replication
      and has facilitated drug discovery efforts. The largest gaps remain in the
      understanding of the virion structure and the processes that lead to the
      assembly, packaging and release of virions. However, given the pace of current
      HCV research, progress in these directions may be expected in the near future.
      Here, we provide a primer on the molecular virology of hepatitis C, with
      particular reference to novel antiviral targets and therapeutic strategies.

PMID- 15566500
TI  - RNA interference--small RNAs effectively fight viral hepatitis.
AB  - RNA interference (RNAi) is the process of sequence-specific gene silencing,
      initiated by double-stranded RNA that is homologous in sequence to the target
      gene. This unique phenomenon has been extensively investigated during the last
      few years not only in the context of its mechanism and its possible role in the
      regulation of gene expression and cell function, but also as a potential powerful
      tool for gene therapy. Targeting essential viral genes or oncogenic alleles are
      only some of the possible applications of RNAi in the field of gene-directed
      therapy. This review covers the potential use of RNAi against hepatitis B and
      hepatitis C viruses, the main pathogens causing chronic liver disease. The major
      milestones along the discovery of RNAi will also be covered.

PMID- 15566501
TI  - How molecular microscopy revealed new insights into the dynamics of hepatic
      endothelial fenestrae in the past decade.
AB  - This review discusses the current state of knowledge about the ultrastructure of
      hepatic endothelial fenestrae. The application of different high-resolution
      correlative microscopic methods during the past decade facilitated the
      accumulation of new insights in the morpho-functional and structural organization
      of the liver sieve. The data gathered unambiguously show the involvement of
      special domains in de novo formation and disappearance of fenestrae, and focuses
      future research into the (supra)molecular structure of the fenestrae-forming
      center, defenestration center and fenestrae-associated cytoskeleton ring by using
      cryo-electron microscopic tomography.

PMID- 15566502
TI  - Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic
      chemotherapy and the role of preemptive lamivudine administration.
AB  - BACKGROUND: Recent data suggest that hepatitis B virus (HBV) reactivation
      develops in 41% of breast cancer (BC) patients carrying HBV after chemotherapy.
      Our study aimed to determine the role of preemptive use of lamivudine in BC
      patients undergoing chemotherapy. PATIENTS AND METHODS: The test group consisted
      of 11 female patients with BC who were seropositive for hepatitis B surface
      antigen (HBsAg). Of these, 10 patients were treated in an adjuvant setting and
      one for metastatic disease. Lamivudine was given from the start of chemotherapy
      and was maintained until 1 month after the last infusion of chemotherapy. The
      control group consisted of nine historical BC patients carrying HBV and received
      similar systemic chemotherapy without preemptive lamivudine. Variables including
      HBsAg, HBV envelope antigen, anti-HBV envelope antibody, serial serum alanine
      transaminase (ALT), quantitative HBV viral DNA analysis, and HBV-DNA precore
      promoter and precore sequence were monitored. Test for emergence of mutant
      strains, notably nucleotide 550, was performed 6 months after the completion of
      chemotherapy. RESULTS: All patients tolerated lamivudine well without development
      of evident HBV reactivation or overt hepatitis. Serum ALT remained unchanged
      without rebound hepatitis after cessation of chemotherapy and withdrawal of
      lamivudine. No emergence of lamivudine-selective resistant strain (so-called
      tyrosine-methionine-aspartate-aspartate mutations) was observed. CONCLUSIONS: Our
      results encourage preemptive use of lamivudine for prevention of HBV reactivation
      in patients who need short-term chemotherapy.

PMID- 15566503
TI  - Lamivudine treatment for acute severe hepatitis B: a pilot study.
AB  - BACKGROUND: Experience with lamivudine treatment of immunocompetent patients with
      acute hepatitis B is limited. AIM OF STUDY: To evaluate the safety and efficacy
      of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection
      in immunocompetent adults. PATIENTS AND METHODS: Fifteen patients (10 men, 5
      women, mean age 34.3+/-7.3 years) with severe acute HBV infection were treated
      with lamivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of
      infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all
      patients had severe coagulopathy (mean INR was 4.5+/-6.4), and all patients had
      evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738+/-1659
      U/L, and mean total serum bilirubin 18+/-6.8 mg/dl). All patients had evidence of
      highly replicative HBV (mean HBV DNA 13.5 x 10(6)+/-11 x 10(6) copies/ml).
      RESULTS: Thirteen patients (86.6%) responded to treatment. Encephalopathy
      disappeared within 3 days of treatment and coagulopathy improved within 1 week.
      Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and
      serum liver enzyme levels normalized within 8 weeks. Two patients in whom
      lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent
      liver transplantation. (One died of vascular complications 1 month later). The 11
      patients who were serum HBeAg-positive before treatment seroconverted, and HBeAb
      developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested
      patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of
      them. Therapy was well tolerated in all cases. CONCLUSIONS: These data indicate
      that lamivudine induces a prompt clinical, biochemical, serological and
      virological response in immunocompetent patients with de novo HBV infection.
      Lamivudine may prevent the progression of severe acute disease to fulminant or
      chronic hepatitis and should be considered for use in selected patients. A large
      randomized controlled, double-blind prospective study is needed.

PMID- 15566504
TI  - Alterations of p53, Bcl-2, and hMSH2 protein expression in the cirrhotic,
      macroregenerative, dysplastic nodules and hepatocellular carcinomas in Upper
      Egypt.
AB  - BACKGROUND: Hepatocarcinogenesis involves alterations in p53, Bcl-2 and human Mut
      S homologue-2 (hMSH2) genes. In Upper Egypt, the clinicopathologic and genetic
      changes during hepatocarcinogensis (cirrhotic nodules (CN); macroregenerative
      nodules (MRN) and dysplastic nodules (DN) are unknown. METHODS: To examine these
      issues, 48 hepatic resection specimens entailing 25 CN, 16 MRN, 23 DN and 48
      hepatocellular carcinoma (HCC) were immunohistochemically evaluated for p53, Bcl
      2 and hMSH2 protein expression. RESULTS: HCC was common in males than in females
      (2.6:1, P<0.05) and with hepatitis C virus than hepatitis B virus infection
      (77.1% vs. 18.7%, P=0.001). p53 expression was found in DN (3/23) and HCC
      (12/48). Its average weighted scores were high in DN/HCC as compared with CN
      (1.60+/-0.40 and 7.20+/-1.20, P=0.0001). Bcl-2 expression was seen in CN, MRN, DN
      and HCC (7/48). Its average weighted scores were high in DN (7.60+/-1.60), HCC
      (6.86+/-0.85) as compared with CN (6.14+/-0.42) and MRN (6.50+/-0.50, P=0.22).
      hMSH2 average weighted scores were reduced in HCC (7.94+/-1.06) as compared with
      CN (8.47+/-0.52), MRN (8.00+/-1.00) and DN (8.20+/-0.80, P>0.05). CONCLUSION: In
      Upper Egypt: (1) HCC had similar clinicopathologic features to those in the high
      risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur
      during hepatocarcinogensis.

PMID- 15566505
TI  - Vigorous response of cytotoxic T lymphocytes associated with systemic activation
      of CD8 T lymphocytes in fulminant hepatitis B.
AB  - BACKGROUND: Fulminant hepatitis is a clinical syndrome characterized by sudden
      and severe liver dysfunction. METHODS: We analyzed two patients with a superacute
      form of fulminant hepatitis B and compared findings with those of four patients
      with acute self-limited hepatitis B, two patients with acute exacerbation of
      chronic hepatitis B and four healthy individuals. RESULTS: In fulminant
      hepatitis, an increased population of human leukocyte antigen (HLA)-DR(+) CD8(+)
      lymphocytes was observed in peripheral blood by flow cytometry, which was
      accompanied by the presence of HLA-DR(hi) lymphocytes. The phenotype of CD8(+) T
      lymphocytes from patients with fulminant hepatitis was mostly that of the
      effector T lymphocytes in peripheral blood, whereas lymphocytes with CD45RA(-)
      CCR7(-) phenotype dominated in the liver of these patients. A larger population
      of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) appeared in
      peripheral circulation of the fulminant hepatitis patients compared with that in
      a patient with acute hepatitis. HBV-specific CTLs were highly concentrated in the
      liver, although epitopes recognized by these CTLs in the peripheral blood and in
      the liver were similar. Peripheral CTLs were mostly functional as indicated by
      intracellular perforin and interferon-gamma. CONCLUSIONS: These results suggest
      the presence of vigorous activation of CD8(+) T cells in vivo in fulminant
      hepatitis and the necessity of extensive therapy in patients with this disease.

PMID- 15566506
TI  - Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus
      ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly
      infected with genotype 4.
AB  - AIM: Comparing the efficacy of peginterferon alpha-2b plus ribavirin with
      interferon alpha -2b plus ribavirin in Saudi patients with chronic hepatitis C
      virus (HCV) commonly infected with genotype 4. METHODS: A total of 96 patients
      with chronic HCV infection were randomly assigned to two treatment groups. Forty
      eight patients received once weekly 100 microg of peginterferon alpha-2b plus
      ribavirin given orally 800 mg/day (peginterferon group). Another 48 patients
      received thrice weekly 3 million units of interferon alpha-2b plus ribavirin 800
      mg/day (interferon group). At the end of treatment (48 weeks) and sustained (72
      weeks) biochemical and virologic responses were determined. RESULTS: In the
      peginterferon group, 70.8% (34/48) patients attained both biochemical and
      virologic responses at the end of the treatment as against 52.1% (25/48) patients
      in the interferon group. (P=0.09 for both). Similarly, sustained biochemical and
      virologic responses in the peginterferon group were attained in 52.1% (25/48) and
      43.8% (21/48) patients as against 43.8% (21/48) and 29.2% (14/48) patients in the
      interferon group, respectively (P=0.54 and 0.20, respectively). The sustained
      virologic response rates in patients with genotype 4 were 42.9% (12/28) in the
      peginterferon group and 32.3% (10/31) in the interferon group (P=0.43). Patients
      in peginterferon group had higher, although statistically not significant adverse
      reactions. CONCLUSIONS: Saudi patients with chronic HCV attained a higher,
      although statistically not significant sustained virologic response with
      pegylated interferon plus ribavirin compared with interferon plus ribavirin.

PMID- 15566507
TI  - Clinical significance of elevated alanine aminotransferase in blood donors: a
      follow-up study.
AB  - Alanine aminotransferase (ALT) elevation in blood donors can be related to many
      variables such as viral hepatitis, overweight and ethanol consumption.
      BACKGROUND/AIMS: This study aims to define factors associated with ALT elevation
      in candidates for blood donation, to evaluate ALT levels during follow-up, and to
      establish a histological diagnosis of hepatic disease. METHODS: Alcoholism,
      obesity, drug-induced liver disease, diabetes, hemochromatosis and alpha 1-anti
      trypsin deficiency were investigated in 119 subjects (113 males, six females,
      aged 33.4+/-8.4 years) who were hepatitis B surface antigen/anti-hepatitis C
      virus negative and had been rejected as blood donors as a result of elevated ALT
      (>1.5 times the upper normal limit (UNL) in two determinations). During follow
      up, ALT was determined every 8 weeks and liver biopsy recommended in cases with
      persistently elevated ALT levels. RESULTS: Obesity (30.2%) and alcoholism (28.6%)
      were most frequently associated with ALT elevation and in 9.2% of cases no
      association was found. ALT levels decreased significantly, regardless of the
      associated factor. Liver histology in 40 patients showed steatosis (35%),
      steatohepatitis (30%), non-specific reactive hepatitis (12.5% of cases), normal
      liver (15% of cases) and alcoholic cirrhosis, hemochromatosis and non-specific
      portal fibrosis in three cases. CONCLUSION: ALT levels usually dropped during
      follow-up and although severe hepatic lesions can be found in asymptomatic blood
      donors, mild hepatic damage is the rule.

PMID- 15566508
TI  - Circulating concentrations of interleukin-18, interleukin-18 binding protein, and
      gamma interferon in patients with alcoholic hepatitis.
AB  - BACKGROUND: Alcoholic hepatitis (AH) is associated with dysregulated inflammatory
      and immune responses. interleukin-18 (IL-18), described as gamma interferon
      (gammaIFN)-inducible factor, and its natural antagonist, IL-18 binding protein
      (IL-18 BP), has not been fully studied in patients with AH. Thus, our aim was:
      (i) to determine plasma values of IL-18, IL-18 BP, gammaIFN, and tumor necrosis
      factor alpha (TNF)-alpha in patients hospitalized for biopsy-proven AH; (ii) to
      correlate these cytokines with the severity of AH, as assessed by Maddrey's
      discriminant function (DF), the degree of liver failure using the Child-Pugh
      score and blood neutrophils; (iii) to compare cytokines values in survivors and
      non-survivors. METHODS: Cytokines were measured using specific immunoassays
      within 7 days of admission. The diagnosis of AH was based on histology in all
      cases. We studied 43 cirrhotic patients with a Maddrey's DF>/=32 (severe AH), 29
      patients with a score <32 (non-severe AH), 12 patients with abstinent alcoholic
      cirrhosis, and 10 healthy subjects. RESULTS: IL-18 and TNFalpha were increased in
      severe AH as compared with healthy subjects. Plasma IL-18 BP was elevated in
      patients with severe and non-severe AH as compared with healthy subjects.
      gammaIFN did not differ between groups. In patients with severe and non-severe
      AH, IL-18, IL-18 BP, TNFalpha, but not gammaIFN, were positively correlated to DF
      and Child-Pugh score. Neither IL-18 nor IL-18 BP correlated to TNFalpha. Patients
      who died (n=10) during the hospitalization had higher IL-18 BP and TNFalpha at
      admission as compared with survivors (322 [172-504] vs 222 [109-441] ng/ml; 7.5
      [2.2-17.3] vs 3 [0.6-20] pg/ml, P<0.01, respectively). CONCLUSION: In cirrhotic
      patients with AH, IL-18, IL-18 BP, and TNFalpha correlate to the hepatitis
      severity and to the degree of liver failure. High IL-18 BP and TNFalpha at
      hospital admission in non-survivors suggest it may be of prognostic value.

PMID- 15566509
TI  - Non-alcoholic fatty liver disease--a common and benign finding in octogenarian
      patients.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a common entity in the
      general population, has been shown to be linked with insulin resistance and
      metabolic syndrome. Several of the components of the metabolic syndrome are more
      common in the aged population. The aims of the current study were to determine in
      the aged, the prevalence and the clinical presentation of NAFLD, as well as the
      relation to the underlying metabolic abnormalities. METHOD: In this prospective
      study, we evaluated 91 octogenarians with a mean age of 85.56+/-3.76 years, who
      were admitted to the rehabilitation departments of a geriatric hospital. Clinical
      evaluation included: abdominal ultrasound (US), fasting glucose and lipid levels,
      serum liver enzymes, ferritin, iron and transferrin saturation. Elderly patients
      with NAFLD were compared with 46 young patients with NAFLD. RESULTS: NAFLD
      diagnosed by US was a common finding in this aged population, is present in 42/91
      patients (46.2%). No significant differences were observed between the patients
      with or without NAFLD in the following: age, gender, chronic illnesses,
      anthropometric parameters, lipid profile, fasting glucose levels, metabolic
      syndrome prevalence, serum levels of transaminases, ferritin and iron. Young
      patients with NAFLD had significantly higher serum levels of triglycerides and a
      significantly higher prevalence of glucose intolerance, obesity and the metabolic
      syndrome compared with the elderly patients with NAFLD. CONCLUSIONS: NAFLD was a
      common finding in our group of elderly patients and the prevalence was higher
      than reported in the general population. In contrast to the well-described
      association between the metabolic syndrome and NAFLD in the general population,
      we did not find this association in the aged group. In addition, none of the
      patients had stigmata of advanced liver disease. These data suggest that NAFLD is
      a common and benign finding in the elderly population, but is not associated with
      the metabolic syndrome.

PMID- 15566510
TI  - Randomized trial of three different regimens for 24 weeks for re-treatment of
      chronic hepatitis C patients who failed to respond to interferon-alpha
      monotherapy in Taiwan.
AB  - With the favorable result of interferon (IFN)-ribavirin combination therapy for
      24 weeks among naive Taiwanese chronic hepatitis C (CHC) patients, the optimal
      regimens of re-treatment for CHC patients who failed initial IFN monotherapy is
      not well-established. The study evaluated the effectiveness of re-treatment for
      24 weeks with 3 different regimens and predictors for sustained virological
      response (SVR). METHODS: Total 120 Taiwanese CHC patients (81 males, 70
      relapsers, mean age: 48.6 years) who failed initial IFN monotherapy were
      enrolled. They were assigned randomly (with a ratio of 1:1:2) to receive one of
      the three regimens for re-treatment for 24 weeks; group A: IFN 6 million units
      (MU) monotherapy (N=30), group B: combination therapy with ribavirin and IFN 3 MU
      (N=30) or group C: combination therapy with ribavirin and IFN 6 MU (N=60). The
      intention-to-treat rate of sustained virological response (SVR) was 38.3%. The
      SVR rate in group C (53.3%) was significantly higher than group A (16.7%,
      P<0.005) and group B (30%, P<0.05). Drop-out rates were similar between the three
      groups. Patients achieving SVR had significant improvement histologically.
      Hepatitis C virus (HCV) genotype non-1b infection, lower pretreatment HCV RNA
      levels, combined with ribavirin and with higher IFN dose, and relapsers were
      independent predictors for SVR. CONCLUSION: We concluded that more than one-third
      Taiwanese CHC patients achieved SVR after 24 weeks re-treatment and combination
      therapy, especially with higher dose of IFN, yielded higher efficacy.

PMID- 15566511
TI  - Risk factors for hepatocellular carcinoma in Hepatitis C patients with sustained
      virologic response to interferon therapy.
AB  - BACKGROUND: Although a variety of papers demonstrated inhibited
      hepatocarcinogenesis with interferon (IFN) therapy for chronic hepatitis C, a
      small number of hepatocellular carcinomas (HCCs) were still observed even in
      sustained virologic responders. AIMS: To clarify factors affecting the
      development of HCC, we analyzed the frequency of HCC in sustained virologic
      responders over a long-term observation period. METHODS: Seven hundred and ninety
      two out of the 2623 IFN-treated hepatitis C patients who had undergone liver
      biopsy showed sustained virologic response. Screening for development of HCC was
      performed periodically during an average follow-up of 5.1 years. Fibrosis of the
      pretreatment liver biopsy sample was graded. Risk factors for HCC were analyzed
      by using Cox proportional hazards regression. RESULTS: Of 792 patients, 23
      developed HCC. Univariate analysis showed that stage of hepatic fibrosis, age,
      and alcohol consumption were significantly associated with a risk of HCC
      (P<0.001). There was a significant difference in the cumulative incidence between
      patients stratified according to these variables (P<0.001). CONCLUSIONS:
      Pretreatment hepatic fibrosis score, age, and alcohol consumption may affect
      development of HCC even in sustained virologic responders. Thus, patients with
      these factors should be carefully followed even after eradication of the virus.

PMID- 15566512
TI  - Quantitative assessment of fibrosis in liver biopsies from patients with chronic
      hepatitis B.
AB  - BACKGROUND/AIM: Accurate histological assessment of liver fibrosis is essential
      in the management of chronic hepatitis B (CHB). Although semi-quantitative
      scoring systems describe well the pathological patterns of hepatic structure,
      they produce fibrosis evaluation that is not very precise. Image analysis or
      morphometry has the theoretical advantage of providing truly quantitative data.
      PATIENTS AND METHODS: The present study aimed at validating a new image analysis
      system, Bioquant Nova Prime, in estimating collagen content in liver biopsy
      samples from patients with CHB. The biopsies were stained with picrosirius red
      and the areas of collagen were measured. The results were correlated with
      laboratory parameters and Ishak modified histological scores. Discriminative
      reliability of morphometry was determined using receiver operating
      characteristics (ROC) analysis. RESULTS: There was excellent interobserver
      agreement (r=0.84-0.94, P<0.01) in the morphometric analysis. Significant
      correlations between the quantitative morphometric data and the semi-quantitative
      score (Spearman's r=0.68-0.78, P<0.001) were also demonstrated. Excellent
      discriminative power of morphometry in differentiating mild from advanced
      fibrosis and cirrhosis from absence of cirrhosis was shown by the ROC analysis.
      CONCLUSIONS: Our results validated the use of Bioquant Nova Prime in estimating
      collagen content in liver biopsies. We showed that morphometry is a sensitive
      method of liver fibrosis quantification in CHB and complements semi-quantitative
      histological scoring system. This tool, with its reliable intraassay variability,
      could be of special value in assessing histological response to treatment after
      anti-viral or anti-fibrotic therapy.

PMID- 15566513
TI  - A novel display of reconstruction computed tomography for the detection of small
      hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the usefulness of the alternate display of arterial and
      equilibrium phase images (ADAEI) of 2 mm-pitch reconstruction computed tomography
      (CT) in the detection of hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      One hundred and eleven nodules in 72 patients were confirmed as HCC by radiology,
      histology, or clinical course. Blinded to the outcome, we retrospectively
      reviewed the CT images obtained with dual-phase spiral CT (Radix Prima, Hitachi
      Medical, Tokyo, Japan) by ADAEI and by conventional display on cut films.
      Scanning for the arterial and equilibrium phases was initiated at 33 and 120 s,
      respectively, after starting the injection of contrast medium (iopamidol 3 ml/s)
      with a section thickness of 5 mm and a table feed speed of 5-7 mm/s. In ADAEI,
      all images were reconstructed with a 2-mm interval, and displayed on the monitor
      in an alternating fashion so that an image in the arterial phase was followed by
      the corresponding image in the equilibrium phase, and then by the next pair of
      images in the craniocaudal direction. RESULTS: All 20 HCC nodules larger than 20
      mm in diameter were detected by both ADAEI and the conventional display (NS). On
      the other hand, detectability of smaller HCC nodules was 91/91 (100%) and 72/91
      (79%), respectively (P<0.0001 by McNemar' test). False-positively identified HCC
      nodules, including those diagnosed as possible HCC, were 11 by ADAEI and eight by
      conventional display. CONCLUSION: The novel, alternate display, ADAEI of 2 mm
      pitch reconstruction CT images was useful in detecting small HCC nodules while
      not requiring additional equipment or expense.

PMID- 15566514
TI  - Evaluation of transcatheter arterial embolization prior to percutaneous tumor
      ablation in patients with hepatocellular carcinoma: a randomized controlled
      trial.
AB  - BACKGROUND: Transcatheter arterial embolization (TAE) may reduce the risk of
      hepatocellular carcinoma (HCC) recurrence when performed before percutaneous
      tumor ablation (PTA), either percutaneous ethanol injection therapy (PEIT) or
      radiofrequency ablation (RFA). We conducted a randomized, controlled trial
      comparing the use of TAE combined with percutaneous ethanol injection therapy
      (TAE/PEIT) to the use of PEIT only to assess the effects on HCC recurrence and
      survival. We continued the study after the introduction of RFA and compared TAE
      combined with RFA (TAE/RFA) with RFA only. METHODS: Between March 1997 and April
      2001, 42 HCC patients were enrolled who satisfied the following inclusion
      criteria: (1) uninodular HCC as determined by angiography under computed
      tomography, (2) arterial hypervascularity, and (3) no prior history of HCC
      treatment. Twenty-two patients were treated with TAE/PTA (PEIT, 12; RFA, 10) and
      20 patients with PTA only (PEIT, 14; RFA, 6). RESULTS: There were four cases of
      local recurrence in the PTA-only group and none in the TAE/PTA group (P=0.043).
      The four patients with local recurrence were treated with PEIT. None of the
      patients treated with RFA showed local recurrence. The effect of TAE on overall
      recurrence was not significant (P=0.4179). In the multivariate analysis, prior
      TAE was not significant for survival (P=0.514). CONCLUSIONS: TAE has a limited
      use in suppressing local recurrence when performed before PEIT but not before
      RFA.

PMID- 15566515
TI  - Hepatic iron loading in patients with compound heterozygous HFE mutations.
AB  - AIM: To assess the severity of hepatic iron loading in patients with a compound
      heterozygous C282Y/H63D HFE genotype. METHODS: A total of 246 patients were
      referred to the Hepatology Clinic at a tertiary hospital for HFE genotyping and
      further assessment of elevated serum transferrin saturation and/or ferritin
      results, either with or without abnormal liver function tests. Subjects of the
      study were 19 patients compound heterozygous for HFE who had liver biopsy,
      quantitative liver iron estimation and liver histopathology. RESULTS: Mild iron
      overload [hepatic iron concentration between 30 and 100 micromol/g dry weight],
      was present in 16/19 compound heterozygous patients, three patients had values
      within the reference range. As well as the compound heterozygous HFE genotype,
      18/19 patients were found to have had at least one additional risk factor for
      developing either iron loading or liver disease. CONCLUSION: Compound
      heterozygous patients show no more than mild liver iron loading. The decision
      whether or not to recommend liver biopsy in C282Y/H63D patients with abnormal
      serum iron indices and/or liver function tests should be based on the need to
      evaluate liver damage rather than solely to assess liver iron loading.

PMID- 15566516
TI  - Loss of cooperative function of transforming growth factor-beta signaling
      proteins, smad3 with embryonic liver fodrin, a beta-spectrin, in primary biliary
      cirrhosis.
AB  - Modulation of fibrogenesis, epithelial, and mesenchymal cell fates are prominent
      effects of transforming growth factor-beta (TGF-beta) signaling by Smad proteins.
      We have previously shown that Smad2 and Smad3 insufficiency leads to a loss of
      bile ducts. In addition, Smad3/4 activity is mediated by embryonic liver fodrin
      (ELF), a beta-Spectrin. In mouse elf(-/-) mutants and in liver explant cultures,
      loss of ELF function results in T lymphocytic proliferation and absent
      intrahepatic bile ducts. A similar phenotype is seen in a number of cholestatic
      diseases with progressive loss of intrahepatic bile ducts and fibrosis. However,
      the expression patterns of Smads or role of ELF in cholestatic and fibrotic liver
      diseases are not yet known. METHODS/RESULTS: We investigated the role of ELF in
      primary biliary cirrhosis (PBC), autoimmune hepatitis C, chronic viral hepatitis
      and in livers from mice deficient in Smad2/Smad3. We generated elf(+/-) mutant
      mice and analyzed for chronic liver disease and hepatocellular cancer (HCC) from
      6 to 12 months. Perturbations in ELF expression were consistently seen only in
      PBC tissues. ELF expression was similarly aberrant in tissues from Smad2(+/
      )/Smad3(+/-) mutant mice. Further studies indicated that ELF mislocalization is
      correlated with aberrant localization of Smad3 in some PBC tissues. Thirteen of
      17 elf(+/-) mutant mice developed steatosis, fibrosis, hepatic dysplasia, with
      HCC in two mice. CONCLUSIONS: These results suggest that a compromised
      cytoarchitecture and polarized trafficking of TGF-beta signaling molecules, ELF
      and Smad3 are involved in the pathogenesis of PBC as well as HCC.

PMID- 15566517
TI  - Chemokine receptor 5 and primary biliary cirrhosis: a two-centre genetic
      association study.
AB  - BACKGROUND: Chemokines and their receptors are important mediators of leucocyte
      trafficking and are suggested to be critical for establishment of inflammatory
      autoimmune processes. CC chemokine receptor 5 (CCR5) is expressed preferentially
      by CD4+ T cells. We hypothesised that the CCR5delta(Delta)32 genotype, which
      impairs surface expression of CCR5 in heterozygotes and is linked to a functional
      polymorphism of CD45RA expressed on suppressor-inducer-like 'naive' CD4+ T cells,
      may modulate the inflammatory process in primary biliary cirrhosis (PBC).
      METHODS: CCR5Delta32 polymorphism was determined by PCR in 226 Caucasian PBC
      patients and 197 racially matched controls from two geographical areas,
      Newcastle, UK and Padua, Italy. (UK: 144 PBC, 105 controls, Italy: 82 PBC, 92
      controls). RESULTS: When the two series were analysed separately, there were no
      significant differences in the genotype distribution comparing patients and
      controls (UK: wt/wt 72% vs 76%; wt/Delta32 28% vs 22%; Delta32/Delta32 0% vs 2%,
      P=0.24; Italy: wt/wt 72% vs 82%; wt/Delta32 27% vs 17%; Delta32/Delta32 0% vs 1%,
      P=0.14). However, when the data for the two series were pooled and reanalysed, we
      found an increase in the CCR5Delta32 mutation in PBC patients vs controls (28% vs
      21%, OR=1.43, P=0.03), but there was no evidence that this Delta32 polymorphism
      is associated with less severe disease. CONCLUSIONS: Although this two-centre
      genetic association study is large compared with others performed in PBC, taken
      separately, each geographically based cohort of patients and controls is
      underpowered to detect a small effect of this functional polymorphism. This
      emphasises the need for far larger case-control collections to address which
      polymorphic markers or haplotypes might modify the pathogenesis and clinical
      course of PBC. We propose that multi-centre collaboration on an international
      scale in 'orphan' complex liver diseases such as (PBC) is supported by the
      International Association for the Study of the Liver and promoted via their
      journal with development of a brief format for web-based publication of studies.

PMID- 15566518
TI  - Ultrasound detection of spontaneous hepato-cellular carcinomas in X/myc
      bitransgenic mice.
AB  - AIMS: To evaluate trans-abdominal ultrasound for the detection of Hepatocellular
      carcinoma (HCC) in a bitrasgenic murine (X/myc) model using a commercially
      available high-frequency ultrasound unit. METHODS: Sixty-one female animals were
      included in this study. These animals were submitted to a single ultrasound
      examination of the liver under general anesthesia (isoflurane), and then
      euthanized. Results of ultrasound were compared with necropsy and histopathology.
      RESULTS: The lesions demonstrated a fairly consistent aspect (oval- or round
      shaped, well-defined hypoechoic homogeneous lesions), and lesions as small as 2
      mm were identified. For detection of hepatic nodules per mouse the sensitivity
      was 75%, the specificity was 100% and the accuracy was 88.5%. For detection of
      hepatic focal lesions per lesions the overall sensitivity was 60%, the
      specificity was 97%, and the accuracy was 75.9%. Contrast-enhanced harmonic
      ultrasound imaging did not improve the identification of the lesions in our
      experimental conditions. CONCLUSION: High-frequency ultrasound appears to be an
      efficient tool allowing new possibilities to use this animal model and evaluate
      new therapies in longitudinal studies, which are much more powerful.

PMID- 15566519
TI  - Hypoxia potentiates transforming growth factor-beta expression of hepatocyte
      during the cirrhotic condition in rat liver.
AB  - BACKGROUND/AIMS: Many studies have reported that hypoxia might be associated with
      angiogenesis and fibrogenesis, and the level of transforming growth factor-beta1
      (TGF-beta1) was increased in fibrotic liver and maximal at cirrhosis. Therefore,
      we examined the expression of TGF-beta1, phosphorylated-Smad2/3 (p-Smad2/3) of
      the TGF-beta immediate down stream signaling system and hypoxic status during
      hepatic fibrogenesis. METHODS: Fibrosis of rats was induced by carbon
      tetrachloride. Collagens were detected with Azan stain. Immunohistochemistry and
      immunoblotting was used. RESULTS: TGF-beta1 was mainly produced by hypoxic
      hepatocytes at cirrhosis although myofibroblasts (MFBs) and macrophages producing
      TGF-beta1 were decreased. Moreover, distribution of p-Smad2/3 in hepatocytes was
      consistent with those of hypoxic hepatocytes regardless of MFBs. Furthermore, in
      recovery, most MFBs disappeared, whereas positive reactions of p-Smad2/3 still
      existed in the hepatocytes of hypoxic areas. Therefore, TGF-beta1 expression in
      hepatocytes might have been associated with hypoxia. CONCLUSIONS: We put forward
      the hypothesis that TGF-beta1 is mainly produced by MFBs and macrophages at early
      and middle stages of fibrotic processes, but it is predominantly released by
      hypoxic hepatocytes in the last fibrotic stage or cirrhosis.

PMID- 15566520
TI  - Presence of markers for liver progenitor cells in human-derived intrahepatic
      biliary epithelial cells.
AB  - AIMS: Rodent intrahepatic bile duct may harbor bipotential liver progenitor
      cells. In this study, human-derived intrahepatic biliary epithelial cells (BECs)
      were investigated in terms of whether they have the character of liver progenitor
      cells. METHODS: Ten liver tissue specimens were obtained after partial
      hepatectomy or liver explantation. Intrahepatic BECs were isolated by density
      gradient centrifugation and immunomagnetic separation using anti-human epithelial
      antigen and cultured in medium containing epidermal growth factor and hepatocyte
      growth factor. The isolated and cultured cells were characterized by
      immunostaining and reverse transcription polymerase chain reaction with a variety
      of markers for fetal hepatocytes and liver progenitor cells. RESULTS: These cells
      had proliferated for up to 18 weeks in vitro. They continuously expressed
      epithelial markers (cytokeratin (CK) 8 and CK 18) as well as biliary markers (CK
      7 and CK 19). Remarkably, some isolated and cultured cells also expressed markers
      for fetal hepatocytes and liver progenitor cells, including albumin, alpha
      fetoprotein, alpha1-antitrypsin, c-kit and chromogranin-A. CONCLUSION: Some human
      derived intrahepatic BECs coexpressed markers for liver progenitor cells. This
      finding further supports the hypothesis that the human biliary tree may also
      consist of liver progenitor cells.

PMID- 15566521
TI  - Hydrodynamic-based in vivo transfection of retinoic X receptor-alpha gene can
      enhance vitamin A-induced attenuation of liver fibrosis in mice.
AB  - BACKGROUND/AIM: In hepatic stellate cells isolated from rat fibrotic livers, the
      amount of retinoid X receptor-alpha (RXR-alpha) mRNA is greatly reduced. However,
      the effectiveness of retinoids in the treatment of liver fibrosis is
      controversial. We hypothesized that increasing the expression levels of RXR-alpha
      in livers will improve the response of liver fibrosis to retinoids treatment.
      METHODS: pTracer-CMV2 vector harboring both green fluorescent protein and RXR
      alpha genes was given to mice with carbon tetrachloride (CCl(4))-induced liver
      fibrosis, by hydrodynamic-based in vivo transfection. Vitamin A was
      simultaneously administered to the mice. Sirius red staining and measurement of
      hydroxyproline content were performed to evaluate liver fibrosis. The
      incorporation of 5-bromo-2-deoxyribouridine (BrdU) was carried out to determine
      liver cell proliferation. RESULTS: Successful transfection and expression of
      exogenous RXR-alpha gene in the liver was determined by observance of green
      fluorescence under a confocal microscope, and detection of RXR-alpha protein by
      immunohistochemistry. Hepatic fibrosis, evaluated by both Sirius red staining
      with image analysis and quantity of hydroxyproline in livers of RXR-alpha
      transfected group, tapered off remarkably. The hydroxyproline content and Sirius
      red-positive staining area on liver sections from RXR-alpha-transfected mice
      decreased by 34.3% and 54.63%, respectively, compared with the control group
      receiving empty vector. The labeling index of BrdU in non-parenchymal cells was
      much lower in livers from the RXR-alpha-transfected group than that of empty
      vector-transfected group. CONCLUSIONS: Hydrodynamic-based in vivo transfection of
      the RXR-alpha gene can enhance the vitamin A-induced attenuation of liver
      fibrosis in mice. One of the possible mechanisms of action for this gene
      treatment is inhibition of non-parenchymal cell proliferation mainly composed of
      hepatic stellate cells in fibrotic livers.

PMID- 15566522
TI  - Imatinib mesylate induces apoptosis in human cholangiocarcinoma cells.
AB  - BACKGROUND: Cholangiocarcinoma is a highly malignant, usually fatal cancer with
      limited therapeutic options. Receptor tyrosine kinases contribute to the
      development and progression of this cancer. The relatively selective tyrosine
      kinase inhibitor imatinib mesylate (STI-571 or Gleevec(R)) has recently been
      licensed. However, the ability of this drug to inhibit signal transduction and
      induce apoptosis in human cholangiocarcinoma cells is incompletely studied. Thus,
      our goal was to examine the ability of STI-571 to induce apoptosis in KMCH-1
      cells, a human cholangiocarcinoma cell line. METHODS: Apoptosis was assessed
      morphologically and also biochemically by measuring caspase activity and the
      mitochondrial membrane potential. STI-571 induced apoptosis and inhibited growth
      of KMCH-1 cells in a time- and concentration-dependent manner. The induction of
      apoptosis was accompanied by mitochondrial depolarization followed by a 4.5-fold
      increase in caspase activation and was abrogated by the pancaspase inhibitor z
      VAD(OMe)-fmk. Interestingly, cholangiocarcinoma cells do not express detectable
      PDGFR, c-Abl or c-Kit, which are protein kinases known to be directly inhibited
      by STI-571. However, a significant decrease in epidermal growth factor receptor
      (EGFR) and focal adhesion kinase (FAK) phosphorylation was observed following
      treatment with STI-571. This decrease in EGFR and FAK phosphorylation was
      associated with a reduction in Akt activity resulting in loss of Mcl-1, a potent
      anti-apoptotic Bcl-2 family protein. CONCLUSIONS: These results indicate that STI
      571 induces caspase-dependent apoptosis in a human cholangiocarcinoma cell line
      and suggest that STI-571 might warrant further investigation as a possible agent
      for treatment of human cholangiocarcinoma.

PMID- 15566523
TI  - Influence of large intrahepatic blood vessels on the gross and histological
      characteristics of lesions produced by radiofrequency ablation in a pig liver
      model.
AB  - AIMS: To determine whether the presence of large intrahepatic blood vessels (>/=3
      mm) affect radiofrequency (RF)-induced coagulation necrosis, the gross and
      histological characteristics of RF-ablated areas proximal to or around vessels
      were examined in normal pig livers. METHODS: An RF ablation treatment using a two
      stepwise extension technique produced 12 lesions: six contained vessels (Group
      A), and the other six were localized around vessels (Group B). RESULTS: Gross
      examination revealed that the longest and shortest diameters of the ablated
      lesions were significantly larger in Group B than in Group A. In Group A, patent
      vessels contiguous to the lesion were present in a tongue-shaped area, whereas
      the lesions in Group B were spherical. Staining with nicotinamide adenine
      dinucleotide diaphorase was negative within the ablated area; but, if vessels
      were present in the ablated area, the cells around the vessels in an opposite
      direction to the ablation were stained blue. CONCLUSIONS: Roll-off can be
      achieved with 100% cellular destruction within a lesion that does not contain
      large vessels. The ablated area was decreased in lesions that contained large
      vessels, suggesting that the presence of large vessels in the ablated area
      further increases the cooling effect and may require repeated RF ablation
      treatment to achieve complete coagulation necrosis.

PMID- 15566524
TI  - Multiorgan failure is the commonest cause of death in fulminant hepatic failure:
      a single centre experience.

PMID- 15566525
TI  - Massive hepatic infarction complicating ultrasound-guided percutaneous
      radiofrequency thermal ablation.

PMID- 15566527
TI  - Merging views on assessment.

PMID- 15566529
TI  - Full-curriculum interventions and small-scale studies of transfer: implications
      for psychology-type theory.

PMID- 15566530
TI  - The Network: Towards Unity for Health - 25th anniversary.

PMID- 15566531
TI  - Likert scales: how to (ab)use them.

PMID- 15566532
TI  - What impact will an increased number of teaching general practices have on
      patients, doctors and medical students?
AB  - BACKGROUND: Recommendations for medical training have seen a growing drive for
      undergraduate teaching to take place within the community - primarily in the
      general practice surgery. In light of the ongoing expansion of medical student
      numbers, many more general practices will be required to participate in
      undergraduate teaching. AIM: To explore the perceptions of primary care staff on
      the impact that increasing student numbers will have on them, on their patients
      and on the students themselves. DESIGN OF STUDY: Semi-structured interviews.
      SETTING: Three general practices presently involved in undergraduate teaching, 3
      practices about to become involved in undergraduate teaching and 1 non-teaching
      practice, all in the Black Country area of the West Midlands. METHODS: Semi
      structured interviews with prearranged prompts were undertaken with a variety of
      practice staff including general practitioners (GPs), practice managers and
      practice nurses, as well as administrative and reception staff. RESULTS: Eleven
      GPs, 6 practice managers, 4 practice nurses and 6 receptionists/administrators
      took part in the interviews. Three main themes emerged relating to the effects on
      students and reflecting attitudes towards the Black Country, the experience of
      working among deprived populations and issues around access to the new training
      locations. The majority of interviewees were of the opinion that patients both
      enjoy taking part in undergraduate teaching and are able to benefit from the
      process. Positive impacts on practice infrastructure were also elicited, but when
      asked about the resource implications for the practice of undergraduate teaching,
      there was a dichotomy of opinion. CONCLUSION: For many practices, involvement in
      undergraduate teaching is a double-edged sword.

PMID- 15566533
TI  - Fielding incognito standardised patients as 'known' patients in a controlled
      trial in general practice.
AB  - BACKGROUND: Incognito standardised patients (SPs) have only been used to
      represent new patients so far. The few trials with incognito SPs provide little
      detail on the method used for fielding them. OBJECTIVE: To establish the
      feasibility of introducing SPs as 'known' patients (i.e. patients who have
      previously visited the practice) into practices, to indicate the required
      practice preparations, and to describe the various aspects of using SPs in a
      pretest/post-test design. METHODS: We used incognito SPs as known patients in a
      controlled trial to assess the practice behaviour of 49 trainees. The SPs
      received a 2-day training in role playing and completing checklists. We compiled
      comprehensive practice information folders of each practice to be visited. Real
      personal data and faked medical data of SPs were inserted in the filing system of
      each practice to be visited. Apart from SP roles with slightly different reasons
      for-encounter and different SPs, the same training protocol, checklists and
      practice information folders were used in the post-test. RESULTS: The SPs carried
      out 287 visits in 50 practices. All practices prepared the patient records for
      the SP visits in a fairly authentic practice style. Trainees detected the SP in
      74 visits. The main reasons for detection were imperfections in patient records
      and aspects of SP roles or role playing. CONCLUSION: Fielding incognito SP visits
      as known patients was feasible but labour-intensive. Preparing the SP patient
      records and familiarising SPs with the interior of practices represented new
      elements in the use of SPs. The pretest/post-test format made their use more
      efficient instead of complicating it.

PMID- 15566534
TI  - Learning in a clinical education programme in primary care: the Maastricht
      Adoption Programme.
AB  - INTRODUCTION: At Maastricht University, the integration of knowledge, skills and
      attitudes in preclinical medical education is promoted by an 'Adoption
      Programme', where students carry out assignments in a general practice setting.
      The assignments are explained and discussed in practical medical coaching groups.
      The aim of this study was to examine the relationships between the elements that
      affect learning in the programme. METHOD: Data from the evaluation questionnaires
      of 188 medical students were used to test a causal model of learning in the
      programme. A distinction was made between 'action' and 'reflection on action'. We
      examined the relationships between perceived instructiveness (the programme's
      value as a learning experience) and the following variables: comprehensibility;
      feasibility and execution of the assignments; time spent on the assignments, and
      the direct and indirect influences of the hosting general practitioner (GP) and
      the practical medical coaching group. RESULTS: Performing the assignments had
      little effect on perceived instructiveness. Coaching by the hosting GP influenced
      the execution of assignments mainly by its effect on feasibility. Coaching by the
      GP and in the practical medical coaching groups barely affected perceived
      instructiveness. DISCUSSION AND CONCLUSION: The model gives insight into the
      contribution of aspects of the Adoption Programme to student learning. The
      results are probably negatively influenced by the insufficient priority given to
      the Adoption Programme in the practical medical coaching groups and by inadequate
      instruction given to the GPs for the purposes of their coaching role. More
      careful planning of patient-related assignments is recommended. Reflection on
      assignments and feedback on procedures are needed to lift practical experience
      onto a higher educational level.

PMID- 15566535
TI  - Setting a standard for performance assessment of doctor-patient communication in
      general practice.
AB  - CONTEXT: Continuing professional development (CPD) of general practitioners.
      OBJECTIVE: Criterion-referenced standards for assessing performance in the real
      practice of general practitioners (GPs) should be available to identify learning
      needs or poor performers for CPD. The applicability of common standard setting
      procedures in authentic assessment has not been investigated. METHODS: To set a
      standard for assessment of GP-patient communication with video observation of
      daily practice, we investigated 2 well known examples of 2 different standard
      setting approaches. An Angoff procedure was applied to 8 written cases. A
      borderline regression method was applied to videotaped consultations of 88 GPs.
      The procedures and outcomes were evaluated by the applicability of the procedure,
      the reliability of the standards and the credibility as perceived by the
      stakeholders, namely, the GPs. RESULTS: Both methods are applicable and reliable;
      the obtained standards are credible according to the GPs. CONCLUSIONS: Both
      modified methods can be used to set a standard for assessment in daily practice.
      The context in which the standard will be used - i.e. the specific purpose of the
      standard, the moment the standard must be available or if specific feedback must
      be given - is important because methods differ in practical aspects.

PMID- 15566536
TI  - Competence in the musculoskeletal system: assessing the progression of knowledge
      through an undergraduate medical course.
AB  - BACKGROUND: Professional bodies have expressed concerns that medical students
      lack appropriate knowledge in musculoskeletal medicine despite its high
      prevalence of use within the community. Changes in curriculum and teaching
      strategies may be contributing factors to this. There is little evidence to
      evaluate the degree to which these concerns are justified. OBJECTIVES: To design
      and evaluate an assessment procedure that tests the progress of medical students
      in achieving a core level of knowledge in musculoskeletal medicine during the
      course. PARTICIPANTS AND SETTING: A stratified sample of 136 volunteer students
      from all 5 years of the medical course at Sheffield University. METHODS: The
      progress test concept was adapted to provide a cross-sectional view of student
      knowledge gain during each year of the course. A test was devised which aimed to
      provide an assessment of competence set at the standard required of the newly
      qualified doctor in understanding basic and clinical sciences relevant to
      musculoskeletal medicine. The test was blueprinted against internal and external
      guidelines. It comprised 40 multiple-choice and extended matching questions
      administered by computer. Six musculoskeletal practitioners set the standard
      using a modified Angoff procedure. RESULTS: Test reliability was 0.6 (Cronbach's
      alpha). Mean scores of students increased from 41% in Year 1 to 84% by the final
      year. Data suggest that, from a baseline score in Year 1, there is a disparate
      experience of learning in Year 2 that evens out in Year 3, with knowledge
      progression becoming more consistent thereafter. All final year participants
      scored above the standard predicted by the Angoff procedure. CONCLUSIONS: This
      short computer-based test was a feasible method of estimating student knowledge
      acquisition in musculoskeletal medicine across the undergraduate curriculum.
      Tested students appear to have acquired a satisfactory knowledge base by the end
      of the course. Knowledge gain seemed relatively independent of specialty-specific
      clinical training. Proposals from specialty bodies to include long periods of
      disciplinary teaching may be unnecessary.

PMID- 15566537
TI  - The effect of in-training assessment on clinical confidence in postgraduate
      education.
AB  - INTRODUCTION: The literature on how in-training assessment (ITA) works in
      practice and what educational outcomes can actually be achieved is limited. One
      of the aims of introducing ITA is to increase trainees' clinical confidence; this
      relies on the assumption that assessment drives learning through its content,
      format and programming. The aim of this study was to investigate the effect of
      introducing a structured ITA programme on junior doctors' clinical confidence.
      The programme was aimed at first year trainees in anaesthesiology. METHODS: The
      study involved a nationwide survey of junior doctors' self-confidence in clinical
      performance before (in 2001) and 2 years after (in 2003) the introduction of an
      ITA programme. Respondents indicated confidence on a 155-item questionnaire
      related to performance of clinical skills and tasks reflecting broad aspects of
      competence. A total of 23 of these items related to the ITA programme. RESULTS:
      The response rate was 377/531 (71%) in 2001 and 344/521 (66%) in 2003. There were
      no statistically significant differences in mean levels of confidence before and
      2 years after the introduction of the ITA programme - neither in aspects that
      were related to the programme nor in those that were unrelated to the programme.
      DISCUSSION: This study demonstrates that the introduction of a structured ITA
      programme did not have any significant effect on trainees' mean level of
      confidence on a broad range of aspects of clinical competence. The importance of
      timeliness and rigorousness in the application of ITA is discussed.

PMID- 15566538
TI  - Feasibility and reliability of an in-training assessment programme in an
      undergraduate clerkship.
AB  - INTRODUCTION: Structured assessment, embedded in a training programme, with
      systematic observation, feedback and appropriate documentation may improve the
      reliability of clinical assessment. This type of assessment format is referred to
      as in-training assessment (ITA). The feasibility and reliability of an ITA
      programme in an internal medicine clerkship were evaluated. The programme
      comprised 4 ward-based test formats and 1 outpatient clinic-based test format. Of
      the 4 ward-based test formats, 3 were single-sample tests, consisting of 1
      student-patient encounter, 1 critical appraisal session and 1 case presentation.
      The other ward-based test and the outpatient-based test were multiple sample
      tests, consisting of 12 ward-based case write-ups and 4 long cases in the
      outpatient clinic. In all the ITA programme consisted of 19 assessments. METHODS:
      During 41 months, data were collected from 119 clerks. Feasibility was defined as
      over two thirds of the students obtaining 19 assessments. Reliability was
      estimated by performing generalisability analyses with 19 assessments as items
      and 5 test formats as items. RESULTS: A total of 73 students (69%) completed 19
      assessments. Reliability expressed by the generalisability coefficients was 0.81
      for 19 assessments and 0.55 for 5 test formats. CONCLUSIONS: The ITA programme
      proved to be feasible. Feasibility may be improved by scheduling protected time
      for assessment for both students and staff. Reliability may be improved by more
      frequent use of some of the test formats.

PMID- 15566539
TI  - A model of teaching and learning in the operating theatre.
AB  - INTRODUCTION: This paper extends the work of an earlier publication by the same
      author which reported the findings of a case study designed to investigate how
      medical students learn and are taught in the operating theatre. The earlier paper
      was descriptive in nature, examining the challenges students face as learners in
      theatres. These were conceptualised around 3 key domains: the challenge posed by
      the physical environment; the challenge of the educational task, and the
      challenge of managing and negotiating a role as a participant in the professional
      workplace of theatres. This paper focuses exclusively on the third domain. It
      presents an interpretive model of teaching and learning in the operating theatre,
      drawing largely on conceptual frameworks developed within the literature on
      learning in work-based settings. METHODS: A multimethod strategy included
      observation in theatres, interviews with students and surgeons, and a student
      survey. The themes that characterised the case were identified and the
      relationships among these themes were explored, leading to the development of the
      model. Symbolic interactionism provided the underlying theoretical framework.
      CONCLUSION: In any particular theatre session, the way in which learning evolves
      or is obstructed for any student, and the shape that teaching takes, depends on
      the interpretations that the student and the surgeon make in 'sizing up' the
      teaching and learning environment. How surgeons and students interpret and
      respond to each others' behaviour, style, attitude and even demeanour, has
      consequences for the way teaching and learning develop. The concepts of
      legitimacy and trust underpin these interpretations and are central to
      understanding the processes of teaching and learning in this setting.

PMID- 15566540
TI  - Towards evidence-based practice in medical training: making evaluations more
      meaningful.
AB  - CONTEXT: The evaluation of training is problematic and the evidence base
      inconclusive. This situation may arise for 2 main reasons: training is not
      understood as a complex intervention and, related to this, the evaluation methods
      applied are often overly simplistic. METHOD: This paper makes the case for
      construing training, especially in the field of specialist medical education, as
      a complex intervention. It also selectively reviews the available literature in
      order to match evaluative techniques with the demonstrated complexity.
      CONCLUSIONS: Construing training as a complex intervention can provide a
      framework for selecting the most appropriate methodology to evaluate a given
      training intervention and to appraise the evidence base for training fairly,
      choosing from among both quantitative and qualitative approaches and applying
      measurement at multiple levels of training impact.

PMID- 15566541
TI  - Growth of knowledge in psychiatry and behavioural sciences in a problem-based
      learning curriculum.
AB  - PURPOSE: To evaluate the effectiveness of undergraduate medical education in the
      domains of psychiatry and behavioural sciences, we examined the growth of
      knowledge in those disciplines in a 6-year, problem-based learning (PBL)
      curriculum. Psychiatry and behavioural sciences are taught in the 4 preclinical
      years and in the psychiatric clerkship. The integrative nature of this PBL
      curriculum led us to hypothesise that the knowledge growth curves for these
      disciplines are similar and show a steady upward trend throughout the curriculum.
      METHODS: All items pertaining to psychiatry and behavioural sciences in the
      progress tests administered in the period from September 1993 through May 2001
      were identified. For those items, the percentage of correct scores in the 6 year
      groups were considered a multivariate observation reflecting knowledge growth
      across the 6-year programme. RESULTS: Knowledge growth for psychiatry and
      behavioural sciences increased significantly, from 12% to 59% and from 28% to
      60%, respectively, between Year 1 and the end of Year 6. Apparently, students
      know more about behavioural sciences than about psychiatry when they enter
      medical school, but this difference vanishes in the last 2 years of training.
      Moreover, the growth curves for psychiatry and behavioural sciences started to
      level off after Years 3 and 4, respectively, with no additional significant
      growth in any of the later years. CONCLUSIONS: Psychiatry and behavioural
      sciences showed different patterns of knowledge growth and the 2 growth curves
      levelled off in Years 5 through 6. Because a student-centred, horizontally and
      vertically integrated PBL curriculum is aimed at effecting steady growth in
      knowledge in all disciplines, the slowdown in growth in the later years was among
      the reasons for initiating a major curricular innovation in 2001.

PMID- 15566542
TI  - The structure of reflective practice in medicine.
AB  - BACKGROUND: The capability to reflect consciously upon one's professional
      practice is generally considered important for the development of expertise and,
      hence, for education. However, to our knowledge no empirical research has been
      conducted to date into the nature of reflective practice in medicine. PURPOSE: To
      study the structure of reflective practice in medicine. METHODS: A questionnaire
      based on the literature was developed and administered to a group of primary care
      doctors. The data were subjected to confirmatory factor analysis using structural
      equations modelling. RESULTS: A 5-factor model of reflective practice emerged. It
      consisted of the following factors: deliberate induction; deliberate deduction;
      testing and synthesising; openness for reflection, and meta-reasoning. The model
      fitted the data sufficiently. CONCLUSION: A multidimensional structure of
      reflective practice in medicine was brought to light by the study. Its components
      in terms of reasoning processes, behaviours and attitudes were identified and
      measured among doctors. Once conceptualised and measured, reflective practice can
      be studied to gain a better understanding of its relation to expertise
      development in medicine. In addition, training students to apply reflective
      practices may become a goal in medical education.

PMID- 15566543
TI  - Curriculum for complex humanitarian emergencies is urgently needed.

PMID- 15566544
TI  - Constraints on conceptual development: a case study of the acquisition of
      folkbiological and folksociological knowledge in Madagascar.
AB  - How different are the concepts held by children who grow up in a North American
      middle class neighborhood and by children who grow up in a rural Malagasy fishing
      village? By probing Malagasy children's and adults' conceptual representations of
      human and animal kind, biological inheritance, innate potential and family
      relations, the studies presented in this Monograph address current debates about
      the acquisition and the nature of concepts in the domains of folkbiology and
      folksociology. Cross-cultural and developmental studies of this kind bear on the
      hypothesis that conceptual development in these domains is supported and
      constrained by innate conceptual content. If so, one would expect cross-cultural
      universality in the relevant adult concepts and their early emergence in
      childhood regardless of widely different input conditions. We chose to conduct
      these studies among the Vezo of Madagascar because the ethnographic literature
      has attributed to them folkbiological and folksociological theories that are
      radically different, even in commensurable, with those of North American adults.
      Vezo therefore provide a challenging test for the innate conceptual constraints
      hypothesis.Four studies probed aspects of biological and sociological reasoning
      of Vezo children, adolescents and adults through a number of adoption scenarios.
      Despite ethnographic reports to the contrary, we found cross-cultural convergence
      in adult concepts of biological inheritance, but the pattern of development of
      this concept differed greatly from that seen in North America. Moreover, in
      agreement with the ethnographic literature, we found that Vezo adults have
      constructed a distinctive theory of social group identity. However, we found that
      children's reasoning in this domain is under the influence of endogenous
      constraints that are overturned in the course of development. Finally, we found
      cross-cultural convergence in adults' concept of species kind, as well as
      evidence for the early emergence of this concept. In light of these findings, we
      discuss the nature of the constraints on children's conceptual representations,
      the developmental process through which the adults' concepts are constructed, and
      relations between Vezotheories of folkbiology and folksociology.

PMID- 15566554
TI  - Public money, public values.

PMID- 15566555
TI  - Child abuse prevention in Japan: an approach to screening and intervention with
      mothers.
AB  - The number of reported child abuse cases is on the increase in Japan. This report
      describes the testing of an approach to prevention based on a key question: "Do
      you find any of your children irritating?" The study employed a focus group and a
      survey. The focus group consisted of 13 mothers who had been severely abusive to
      their children and were undergoing individual psychotherapy in Tokyo. The survey
      included 1,538 mothers living with at least one child less than 6 years of age in
      metropolitan Tokyo. The survey questionnaire asked about mothers' attitudes
      toward their children and about details and frequency of possibly abusive
      behavior for their children. All 13 mothers of the focus group reported the
      experience of feeling their children irritating. They talked extensively and
      provided many details of their feelings. Of the survey mothers, 3.6% reported
      feeling their children irritating and showed high scores of abusive behavior.
      There was a difference in attribution of source of the irritation between these
      mothers and focus-group mothers. We conclude that the question on irritability is
      effective in eliciting mothers' feelings and behavior, especially for providing
      public health nurses with an opportunity for intervention in child abuse.

PMID- 15566556
TI  - Latino immigrants' knowledge of tuberculosis.
AB  - This study examined tuberculosis (TB) knowledge in Latino immigrants receiving
      latent TB infection (LTBI) therapy. The study design was descriptive
      correlational. Knowledge was measured using the LTBI Knowledge Instrument. The
      convenience sample included 82 Latino immigrants primarily from Central America
      and Bolivia who attended a public health clinic for their LTBI therapy. The mean
      TB knowledge score was 66%. Knowledge scores were correlated with years of
      education, but not with age or number of years in the United States. More than
      80% of study participants correctly answered questions about the importance of
      keeping monthly appointments and how Isoniazid works to eradicate TB germs in the
      human body. Questions that pertained to the contagiousness of active TB and how
      the disease spreads received the most incorrect responses. Public health nursing
      interventions should focus on increasing Latino immigrants' knowledge of TB, both
      in public health clinics and in the community.

PMID- 15566557
TI  - Cardiovascular disease: application of a composite risk index from the Telehealth
      System in a district community.
AB  - Assessing a combination of cardiovascular disease (CVD)-risk factors may be a
      practical tool for risk assessment and for finding the high-risk group among
      local community members. This study examines the association between the number
      of CVD-risk factors, regardless of any specific combination with the CVD ambit,
      using data from 1,570 residents in Tsing Yi community (Hong Kong) who registered
      with the Telehealth System. A quantitative composite CVD Risk Index (CVDRI) with
      scores ranging from 0 to 6 included rankings for high systolic and diastolic
      blood pressure, presence of diabetes, body mass index (BMI), smoking, and age.
      Multivariate logistic regression was used to estimate odds ratios for the
      prevalence of CVD. Those with a CVDRI of 1, 2, or 3 and above were 1.7 [95%
      confidence interval (CI) = 1.34-3.99], 5.3 (95% CI = 3.60-7.90), and 10 times
      (95% CI = 6.41-15.50) more likely to have CVD, respectively, than those with a
      risk index of 0. Among the CVDRI components, high blood pressure had the greatest
      influence on CVD risk, followed by presence of diabetes and high BMI. In
      conclusion, a CVDRI based on existing health data from a Telehealth System was
      developed and used to identify local community members at risk of CVD. Nurse
      intervention may achieve greater reduction of CVD morbidity and mortality if
      multiple risk factors for the high-risk group are addressed at the same time.

PMID- 15566558
TI  - Physical and psychosocial health in family caregiving: a comparison of AIDS and
      cancer caregivers.
AB  - The objectives of this study were to compare cancer and AIDS family caregivers in
      regard to their physical and emotional health. The sample consisted of 26
      caregivers of persons with cancer or AIDS. Study participants completed a
      questionnaire that included measures of depression, grief, symptoms of stress,
      caregiving demands, interpersonal relationships, health status, and quality of
      life. The data revealed that both AIDS and cancer caregivers reported high levels
      of stress and depression as compared to community norms. No significant
      differences were found between AIDS and cancer caregivers for any of the scale
      scores; however, the two groups differed on several individual subscales. Cancer
      caregivers demonstrated higher social functioning and were more likely to report
      that the work of caregiving itself disrupted their ability to socially engage
      with others. In contrast, AIDS caregivers were more likely to report that their
      own health limited their ability to socialize. Even though AIDS caregivers
      experienced less family support than cancer caregivers, they reported more
      rewards from caregiving. Results suggest that support delivered to caregivers
      emphasize a more inclusive approach to program delivery, versus a disease
      specific perspective, in order to increase the depth and breath of services
      provided to families undertaking these challenges.

PMID- 15566559
TI  - Qualitative evaluation of South Carolina's Postpartum/Infant Home Visit program.
AB  - Many states have introduced home visitation programs to improve the health of
      mothers and newborn infants. In South Carolina, the Postpartum/Infant Home Visit
      (P/IHV) program seeks to provide all Medicaid-eligible mothers and infants with
      at least one home visit by a nurse or other qualified health professional. In the
      summer 2002, the authors conducted a cost-benefit analysis of the P/IHV program
      using both qualitative and quantitative methods. This article describes the
      qualitative methods and findings from the larger study. Focus groups were held
      with nurses who provide P/IHV visits to gain insight into the structure and
      functioning of the P/IHV program, to hear firsthand the nurses' experiences with
      the program, and to provide guidance in developing the empiric model for
      measuring cost-benefit. Analysis of the focus-group data suggests that what
      actually occurs during a home visit is fairly standardized. Nurses indicated that
      they were knowledgeable about community resources and services available to the
      families they serve. Referral processes were identified as an important factor in
      determining whether a mother receives a home visit. Overall, the nurses felt that
      the home visit program has had a positive impact on the health and well-being of
      the mothers and infants served.

PMID- 15566560
TI  - Using geographic information systems to design population-based interventions.
AB  - Geographic information systems (GIS) offer public health nurses a new technology
      to plan and implement interventions within communities. The present article gives
      a brief overview of GIS, describes a project designed to pilot-test the use of
      GIS for developing population-based interventions, and discusses lessons learned
      from the project that need to be applied to any future work. Using GIS to map the
      incidence and prevalence of disease, locate risk factors, and identify access to
      health care services is not difficult. Trying to move beyond that and use the
      technology to depict community networks and develop and implement population
      based interventions is more problematic. The project identified specific
      questions that anyone involved in a planning or decision-making project in which
      GIS are used should ask.

PMID- 15566561
TI  - Workplace variables and their relationship to quality client outcomes in home
      health.
AB  - The purpose of the study was to investigate the relationship of workplace
      variables and client outcomes, and to propose a model of the fit between the
      workplace variable dimensions of nursing technology (NT) and organizational
      structure (OS) to predict client outcomes in home health. The researchers used a
      correlational, predictive, descriptive design to measure NT, OS, nurses' role
      clarity, client outcomes, and client satisfaction. A convenience sample consisted
      of 43 home health sites with 205 nurses and 325 clients completing surveys.
      Nurses perceived that clients had better outcomes when the three dimensions of NT
      fit the three dimensions of OS: (1) when clients' conditions were unstable,
      nurses interacted with peers; (2) when care was complex, nurses consulted with
      supervisors; and (3) when clients' needs varied, nurses used rules to guide
      clinical decisions. Findings suggested that nurses' understanding of their roles
      correlated to OS. Nurse managers in home health care settings can use the model
      constructed as a result of the research to adjust the dimensions of OS to improve
      client outcomes.

PMID- 15566562
TI  - Organizational structure and job satisfaction in public health nursing.
AB  - The purpose of this descriptive study was to describe the characteristics and
      relationship of organizational structure and job satisfaction in public health
      nursing. A significant relationship was found between organizational structure
      variables and job satisfaction for public health nurses employed in down state
      Illinois local health departments. The findings of this study suggest that work
      environments in which supervisors and subordinates consult together concerning
      job tasks and decisions, and in which individuals are involved with peers in
      decision making and task definition, are positively related to job satisfaction.
      This information will assist nurse administrators in development of work
      structures that support participative decision making and enhance job
      satisfaction, critical to retaining and attracting a well-qualified public health
      nurse workforce.

PMID- 15566563
TI  - Helping people is a democratic process. 1948.
AB  - Editor's Note Deciding when to assist and when to stand back so that individuals
      may follow their own desires has been a source of much public debate in the last
      few years with respect to health behaviors, social structures, and also political
      beliefs. The following short essay, published in the July 1948 issue of the first
      Public Health Nursing, illustrates, first, that from flawed logic we derive
      flawed conclusions, but also maybe a modicum of truth. Secondly, it aptly
      highlights the conundrum of "incentives" and the disillusionment of well-meaning
      "givers" when the recipients do not view our "gifts" through the same lens. We do
      not subscribe to the views of Ms. King, but rather raise the following questions
      for your consideration, "When we give, how much are we meeting our own needs
      rather than the needs of others?""Can a society be empathic without losing its
      own sense of identity?" Things to ponder in this holiday season ...

PMID- 15566564
TI  - Integrating partonomic hierarchies in anatomy ontologies.
AB  - BACKGROUND: Anatomy ontologies play an increasingly important role in developing
      integrated bioinformatics applications. One of the primary relationships between
      anatomical tissues represented in such ontologies is part-of. As there are a
      number of ways to divide up the anatomical structure of an organism, each may be
      represented by more than one valid partonomic (part-of) hierarchy. This raises
      the issue of how to represent and integrate multiple such hierarchies. RESULTS:
      In this paper we describe a solution that is based on our work on an anatomy
      ontology for mouse embryo development, which is part of the Edinburgh Mouse Atlas
      Project (EMAP). The paper describes the basic conceptual aspects of our approach
      and discusses strengths and limitations of the proposed solution. A prototype was
      implemented in Prolog for evaluation purposes. CONCLUSION: With the proposed name
      set approach, rather than having to standardise hierarchies, it is sufficient to
      agree on a suitable set of basic tissue terms and their meaning in order to
      facilitate the integration of multiple partonomic hierarchies.

PMID- 15566565
TI  - Immunodominant PstS1 antigen of mycobacterium tuberculosis is a potent biological
      response modifier for the treatment of bladder cancer.
AB  - BACKGROUND: Bacillus Calmette Guerin (BCG)-immunotherapy has a well-documented
      and successful clinical history in the treatment of bladder cancer. However,
      regularly observed side effects, a certain degree of nonresponders and
      restriction to superficial cancers remain a major obstacle. Therefore,
      alternative treatment strategies are intensively being explored. We report a
      novel approach of using a well defined immunostimulatory component of
      Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate
      transport protein PstS1 which represents the phosphate binding component of a
      mycobacterial phosphate uptake system is known to be a potent immunostimulatory
      antigen of M. tuberculosis. This preclinical study was designed to test the
      potential of recombinant PstS1 to serve as a non-viable and defined
      immunotherapeutic agent for intravesical bladder cancer therapy. METHODS:
      Mononuclear cells (PBMCs) were isolated from human peripheral blood and
      stimulated with PstS1 for seven days. The activation of PBMCs was determined by
      chromium release assay, IFN-gamma ELISA and measurement of lymphocyte
      proliferation. The potential of PstS1 to activate monocyte-derived human
      dendritic cells (DC) was determined by flow cytometric analysis of the marker
      molecules CD83 and CD86 as well as the release of the cytokines TNF-alpha and IL
      12. Survival of presensitized and intravesically treated, tumor-bearing mice was
      analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune
      response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA,
      splenocyte proliferation assay and immunohistochemistry. RESULTS: Our in vitro
      experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-gamma
      release and proliferation of PBMCs. Further investigations showed the potential
      of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies
      in an orthotopic murine bladder cancer model demonstrated the therapeutic
      potential of intravesically applied PstS1. Immunohistochemical analysis and
      splenocyte restimulation assay revealed that local and systemic immune responses
      were triggered by intravesical PstS1-immunotherapy. CONCLUSION: Our results
      demonstrate profound in vitro activation of human immune cells by recombinant
      PstS1. In addition, intravesical PstS1 immunotherapy induced strong local and
      systemic immune responses together with substantial anti-tumor activity in a
      preclinical mouse model. Thus, we have identified recombinant PstS1 antigen as a
      potent immunotherapeutic drug for cancer therapy.

PMID- 15566566
TI  - Negative and positive childhood experiences across developmental periods in
      psychiatric patients with different diagnoses - an explorative study.
AB  - BACKGROUND: A high frequency of childhood abuse has often been reported in adult
      psychiatric patients. The present survey explores the relationship between
      psychiatric diagnoses and positive and negative life events during childhood and
      adulthood in psychiatric samples. METHODS: A total of 192 patients with diagnoses
      of alcohol-related disorders (n = 45), schizophrenic disorders (n = 52),
      affective disorders (n = 54), and personality disorders (n = 41) completed a 42
      item self-rating scale (Traumatic Antecedents Questionnaire, TAQ). The TAQ
      assesses personal positive experiences (competence and safety) and negative
      experiences (neglect, separation, secrets, emotional, physical and sexual abuse,
      trauma witnessing, other traumas, and alcohol and drugs abuse) during four
      developmental periods, beginning from early childhood to adulthood. Patients were
      recruited from four Psychiatric hospitals in Germany, Switzerland, and Romania;
      63 subjects without any history of mental illness served as controls. RESULTS:
      The amount of positive experiences did not differ significantly among groups,
      except for safety scores that were lower in patients with personality disorders
      as compared to the other groups. On the other side, negative experiences appeared
      more frequently in patients than in controls. Emotional neglect and abuse were
      reported in patients more frequently than physical and sexual abuse, with
      negative experiences encountered more often in late childhood and adolescence
      than in early childhood. The patients with alcohol-related and personality
      disorders reported more negative events than the ones with schizophrenic and
      affective disorders. CONCLUSIONS: The present findings add evidence to the
      relationship between retrospectively reported childhood experiences and
      psychiatric diagnoses, and emphasize the fact that a) emotional neglect and abuse
      are the most prominent negative experiences, b) adolescence is a more 'sensitive'
      period for negative experiences as compared to early childhood, and c) a high
      amount of reported emotional and physical abuse occurs in patients with alcohol
      related and personality disorders respectively.

PMID- 15566567
TI  - Endodontic flare-ups: comparison of incidence between single and multiple visit
      procedures in patients attending a Nigerian teaching hospital.
AB  - BACKGROUND: Until recently the most accepted technique of doing root canal
      treatment stresses multiple visit procedure. Most schools also concentrated upon
      teaching the multi-visit concept. However, it has now been reported that the
      procedure of single visit treatment is advocated by at least 70% of schools in
      all geographical areas. It was therefore the aims of the present study to find
      the incidence of post-obturation flare-ups following single and multiple visit
      endodontic treatment procedures, and to establish the relationship between pre
      operative and post-obturation pain in patients referred for endodontic therapy in
      a Nigerian teaching Hospital. METHODS: Data collected included pulp vitality
      status, the presence or absence of pre-operative, inter-appointment and post
      obturation pain. Pain was recorded as none, slight, or moderate/severe. Flare-ups
      were defined as either patient's report of pain not controlled with over the
      counter medication or as increasing swelling. The patients were recalled at three
      specific post-obturation periods, 1st, 7th and 30th day. The presence or absence
      of pain, or the appropriate degree of pain was recorded for each recall visits
      and the interval between visits. The compiled data were analysed using chi-square
      where applicable. P level </= 0.05 was taken as significant. RESULTS: Ten
      endodontic flare-ups (8.1%) were recorded in the multiple visit group compared to
      19 (18.3%) flare-ups for the single visit group, P = 0.02. For both single and
      multiple visit procedures, there were statistically significant correlations
      between pre-operative and post-obturation pain (P = 0.002 and P = 0.0004
      respectively). Teeth with vital pulps reported the lowest frequency of post
      obturation pain (48.8%), while those with nonvital pulps were found to have the
      highest frequency of post-obturation pain (50.3%), P = 0.9. CONCLUSION: The
      present study reported higher incidences of post-obturation pain and flare-ups
      following the single visit procedures. However, single visit endodontic therapy
      has been shown to be a safe and effective alternative to multiple visit
      treatment, especially in communities where patients default after the first
      appointment at which pain is relieved.

PMID- 15566568
TI  - The establishment and characterization of the first canine hepatocellular
      carcinoma cell line, which resembles human oncogenic expression patterns.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most worldwide frequent
      primary carcinomas resulting in the death of many cirrhotic patients.
      Unfortunately, the molecular mechanisms of this cancer are not well understood;
      therefore, we need a good model system to study HCC. The dog is recognized as a
      promising model for human medical research, namely compared with rodents. The
      objective of this study was to establish and characterize a spontaneous canine
      tumor cell line as a potential model for studies on HCC. RESULTS:
      Histomorphological, biochemical, molecular biological and quantitative assays
      were performed to characterize the canine HCC cell line that originated from a
      dog with a spontaneous liver tumor. Morphological investigations provided strong
      evidence for the hepatocytic and neoplastic nature of the cell line, while
      biochemical assays showed that they produced liver-specific enzymes. PCR analysis
      confirmed expression of ceruloplasmin, alpha-fetoprotein and serum albumin.
      Quantitative RT-PCR showed that the canine HCC cell line resembles human HCC
      based on the measurements of expression profiles of genes involved in cell
      proliferation and apoptosis. CONCLUSIONS: We have developed a novel, spontaneous
      tumor liver cell line of canine origin that has many characteristics of human
      HCC. Therefore, the canine HCC cell line might be an excellent model for
      comparative studies on the molecular pathogenesis of HCC.

PMID- 15566569
TI  - Evolutionary relationships of Fusobacterium nucleatum based on phylogenetic
      analysis and comparative genomics.
AB  - BACKGROUND: The phylogenetic position and evolutionary relationships of
      Fusobacteria remain uncertain. Especially intriguing is their relatedness to low
      G+C Gram positive bacteria (Firmicutes) by ribosomal molecular phylogenies, but
      their possession of a typical gram negative outer membrane. Taking advantage of
      the recent completion of the Fusobacterium nucleatum genome sequence we have
      examined the evolutionary relationships of Fusobacterium genes by phylogenetic
      analysis and comparative genomics tools. RESULTS: The data indicate that
      Fusobacterium has a core genome of a very different nature to other bacterial
      lineages, and branches out at the base of Firmicutes. However, depending on the
      method used, 35-56% of Fusobacterium genes appear to have a xenologous origin
      from bacteroidetes, proteobacteria, spirochaetes and the Firmicutes themselves. A
      high number of hypothetical ORFs with unusual codon usage and short lengths were
      found and hypothesized to be remnants of transferred genes that were discarded.
      Some proteins and operons are also hypothesized to be of mixed ancestry. A large
      portion of the Gram-negative cell wall-related genes seems to have been
      transferred from proteobacteria. CONCLUSIONS: Many instances of similarity to
      other inhabitants of the dental plaque that have been sequenced were found. This
      suggests that the close physical contact found in this environment might
      facilitate horizontal gene transfer, supporting the idea of niche-specific gene
      pools. We hypothesize that at a point in time, probably associated to the rise of
      mammals, a strong selective pressure might have existed for a cell with a
      Clostridia-like metabolic apparatus but with the adhesive and immune camouflage
      features of Proteobacteria.

PMID- 15566570
TI  - Magnetic techniques for the isolation and purification of proteins and peptides.
AB  - Isolation and separation of specific molecules is used in almost all areas of
      biosciences and biotechnology. Diverse procedures can be used to achieve this
      goal. Recently, increased attention has been paid to the development and
      application of magnetic separation techniques, which employ small magnetic
      particles. The purpose of this review paper is to summarize various
      methodologies, strategies and materials which can be used for the isolation and
      purification of target proteins and peptides with the help of magnetic field. An
      extensive list of realised purification procedures documents the efficiency of
      magnetic separation techniques.

PMID- 15566571
TI  - Adoptive immunotherapy of cancer with polyclonal, 108-fold hyperexpanded, CD4+
      and CD8+ T cells.
AB  - T cell-mediated cancer immunotherapy is dose dependent and optimally requires
      participation of antigen-specific CD4+ and CD8+ T cells. Here, we isolated tumor
      sensitized T cells and activated them in vitro using conditions that led to
      greater than 108-fold numerical hyperexpansion of either the CD4+ or CD8+ subset
      while retaining their capacity for in vivo therapeutic efficacy. Murine tumor
      draining lymph node (TDLN) cells were segregated to purify the CD62Llow subset,
      or the CD4+ subset thereof. Cells were then propagated through multiple cycles of
      anti-CD3 activation with IL-2 + IL-7 for the CD8+ subset, or IL-7 + IL-23 for the
      CD4+ subset. A broad repertoire of TCR Vbeta families was maintained throughout
      hyperexpansion, which was similar to the starting population. Adoptive transfer
      of hyper-expanded CD8+ T cells eliminated established pulmonary metastases, in an
      immunologically specific fashion without the requirement for adjunct IL-2. Hyper
      expanded CD4+ T cells cured established tumors in intracranial or subcutaneous
      sites that were not susceptible to CD8+ T cells alone. Because accessibility and
      antigen presentation within metastases varies according to anatomic site,
      maintenance of a broad repertoire of both CD4+ and CD8+ T effector cells will
      augment the overall systemic efficacy of adoptive immunotherapy.

PMID- 15566572
TI  - Antitumor effectiveness of different amounts of electrical charge in Ehrlich and
      fibrosarcoma Sa-37 tumors.
AB  - BACKGROUND: In vivo studies were conducted to quantify the effectiveness of low
      level direct electric current for different amounts of electrical charge and the
      survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct
      electric in Ehrlich tumor was evaluate through the measurements of tumor volume
      and the peritumoral and tumoral findings. METHODS: BALB/c male mice, 7-8 week old
      and 20-22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing
      in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors,
      located dorsolaterally in animals, were initiated by the inoculation of 5 x 10(6)
      and 1 x 10(5) viable tumor cells, respectively. For each type of tumor four
      groups (one control group and three treated groups) consisting of 10 mice
      randomly divided were formed. When the tumors reached approximately 0.5 cm3, four
      platinum electrodes were inserted into their bases. The electric charge delivered
      to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of
      45 minutes. An additional experiment was performed in BALB/c male mice bearing
      Ehrlich tumor to examine from a histolological point of view the effects of
      direct electric current. A control group and a treated group with 77 C/cm3 (27.0
      C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the
      tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into
      the base perpendicular to the tumor long axis. RESULTS: Significant tumor growth
      delay and survival rate were achieved after electrotherapy and both were
      dependent on direct electric current intensity, being more marked in fibrosarcoma
      Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were
      observed for electrical charges of 80 and 92 C/cm3, respectively.
      Histopathological and peritumoral findings in Ehrlich tumor revealed in the
      treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil
      infiltration, an acute inflammatory response, and a moderate peritumoral monocyte
      infiltration. The morphologic pattern of necrotic cell mass after direct electric
      current treatment is the coagulative necrosis. These findings were not observed
      in any of the untreated tumors. CONCLUSION: The data presented indicate that
      electrotherapy with low-level DEC is feasible and effective in the treatment of
      the Ehrlich and fibrosarcoma Sa-37 tumors. Our results demonstrate that the
      sensitivity of these tumors to direct electric current and survival rates of the
      mice depended on both the amount of electrical charge and the type of tumor. Also
      the complete regression of each type of tumor is obtained for a threshold amount
      of electrical charge.

PMID- 15566573
TI  - Expression of leukemia inhibitory factor (LIF) and its receptor gp190 in human
      liver and in cultured human liver myofibroblasts. Cloning of new isoforms of LIF
      mRNA.
AB  - BACKGROUND: The cytokine leukemia inhibitory factor (LIF) mediates its biological
      effects through binding to its high affinity receptor made of the low-affinity
      LIF receptor subunit gp190 (LIF-R) and the gp130 subunit. LIF exerts several
      important effects in the liver, however, data on liver expression of LIF are
      scarce. The aim of this study was to examine the expression of LIF and LIF-R in
      human liver. RESULTS: LIF expression, analyzed by immunohistochemistry, was
      barely detectable in normal liver but was strong within cirrhotic fibrous septa
      and was found in spindle-shaped cells compatible with myofibroblasts.
      Accordingly, cultured human liver myofibroblasts expressed high levels of LIF as
      shown by ELISA and Northern blot. Biological assay demonstrated that
      myofibroblast-derived LIF was fully active. RT-PCR showed expression of the LIF-D
      and M isoforms, and also of low levels of new variants of LIF-D and LIF-M
      resulting from deletion of exon 2 through alternative splicing. LIF receptor
      expression was detected mainly as a continuous sinusoidal staining that was
      enhanced in cirrhotic liver, suggestive of endothelial cell and/or hepatocyte
      labeling. Immunohistochemistry, flow cytometry and STAT-3 phosphorylation assays
      did not provide evidence for LIF receptor expression by myofibroblasts
      themselves. LIF secretion by cultured myofibroblasts was down regulated by the
      addition of interleukin-4. CONCLUSIONS: We show for the first time the expression
      of LIF in human liver myofibroblasts, as well as of two new isoforms of LIF mRNA.
      Expression of LIF by myofibroblasts and of its receptor by adjacent cells
      suggests a potential LIF paracrine loop in human liver that may play a role in
      the regulation of intra-hepatic inflammation.

PMID- 15566574
TI  - Predictors of mortality of patients with acute respiratory failure secondary to
      chronic obstructive pulmonary disease admitted to an intensive care unit: a one
      year study.
AB  - BACKGROUND: Patients with acute exacerbation of chronic obstructive pulmonary
      disease (COPD) commonly require hospitalization and admission to intensive care
      unit (ICU). It is useful to identify patients at the time of admission who are
      likely to have poor outcome. This study was carried out to define the predictors
      of mortality in patients with acute exacerbation of COPD and to device a scoring
      system using the baseline physiological variables for prognosticating these
      patients. METHODS: Eighty-two patients with acute respiratory failure secondary
      to COPD admitted to medical ICU over a one-year period were included. Clinical
      and demographic profile at the time of admission to ICU including APACHE II score
      and Glasgow coma scale were recorded at the time of admission to ICU. In
      addition, acid base disorders, renal functions, liver functions and serum
      albumin, were recorded at the time of presentation. Primary outcome measure was
      hospital mortality. RESULTS: Invasive ventilation was required in 69 patients
      (84.1%). Fifty-two patients survived to hospital discharge (63.4%). APACHE II
      score at the time of admission to ICU {odds ratio (95 % CI): 1.32 (1.138-1.532);
      p < 0.001} and serum albumin (done within 24 hours of admission) {odds ratio (95
      % CI): 0.114 (0.03-0.432); p = 0.001}. An equation, constructed using the
      adjusted odds ratio for the two parameters, had an area under the ROC curve of
      91.3%. For the choice of cut-off, sensitivity, specificity, positive and negative
      predictive value for predicting outcome was 90%, 86.5%, 79.4% and 93.7%.
      CONCLUSION: APACHE II score at admission and SA levels with in 24 hrs after
      admission are independent predictors of mortality for patients with COPD admitted
      to ICU. The equation derived from these two parameters is useful for predicting
      outcome of these patients.

PMID- 15566575
TI  - Inhibition of c-Jun NH2-terminal kinase or extracellular signal-regulated kinase
      improves lung injury.
AB  - BACKGROUND: Although in vitro studies have determined that the activation of
      mitogen-activated protein (MAP) kinases is crucial to the activation of
      transcription factors and regulation of the production of proinflammatory
      mediators, the roles of c-Jun NH2-terminal kinase (JNK) and extracellular signal
      regulated kinase (ERK) in acute lung injury have not been elucidated. METHODS:
      Saline or lipopolysaccharide (LPS, 6 mg/kg of body weight) was administered
      intratracheally with a 1-hour pretreatment with SP600125 (a JNK inhibitor; 30
      mg/kg, IO), or PD98059 (an MEK/ERK inhibitor; 30 mg/kg, IO). Rats were sacrificed
      4 hours after LPS treatment. RESULTS: SP600125 or PD98059 inhibited LPS-induced
      phosphorylation of JNK and ERK, total protein and LDH activity in BAL fluid, and
      neutrophil influx into the lungs. In addition, these MAP kinase inhibitors
      substantially reduced LPS-induced production of inflammatory mediators, such as
      CINC, MMP-9, and nitric oxide. Inhibition of JNK correlated with suppression of
      NF-kappaB activation through downregulation of phosphorylation and degradation of
      IkappaB-alpha, while ERK inhibition only slightly influenced the NF-kappaB
      pathway. CONCLUSION: JNK and ERK play pivotal roles in LPS-induced acute lung
      injury. Therefore, inhibition of JNK or ERK activity has potential as an
      effective therapeutic strategy in interventions of inflammatory cascade
      associated lung injury.

PMID- 15566576
TI  - Family structure and risk factors for schizophrenia: case-sibling study.
AB  - BACKGROUND: Several family structure-related factors, such as birth order, family
      size, parental age, and age differences to siblings, have been suggested as risk
      factors for schizophrenia. We examined how family-structure-related variables
      modified the risk of schizophrenia in Finnish families with at least one child
      with schizophrenia born from 1950 to 1976. METHODS: We used case-sibling design,
      a variant of the matched case-control design in the analysis. Patients
      hospitalized for schizophrenia between 1969 and 1996 were identified from the
      Finnish Hospital Discharge Register, and their families from the Population
      Register Center. Only families with at least two children (7914 sibships and
      21059 individuals) were included in the analysis. Conditional logistic regression
      with sex, birth cohort, maternal schizophrenia status, and several family-related
      variables as explanatory variables was used in the case-sibling design. The
      effect of variables with the same value in each sibship was analyzed using
      ordinary logistic regression. RESULTS: Having a sibling who was less than five
      years older (OR 1.46, 95% CI 1.29-1.66), or being the firstborn (first born vs.
      second born 1.62, 1.87-1.4) predicted an elevated risk, but having siblings who
      were more than ten years older predicted a lower risk (0.66, 0.56-0.79).
      CONCLUSIONS: Several family-structure-related variables were identified as risk
      factors for schizophrenia. The underlying causative mechanisms are likely to be
      variable.

PMID- 15566577
TI  - Structure and evolution of protein interaction networks: a statistical model for
      link dynamics and gene duplications.
AB  - BACKGROUND: The structure of molecular networks derives from dynamical processes
      on evolutionary time scales. For protein interaction networks, global statistical
      features of their structure can now be inferred consistently from several large
      throughput datasets. Understanding the underlying evolutionary dynamics is
      crucial for discerning random parts of the network from biologically important
      properties shaped by natural selection. RESULTS: We present a detailed
      statistical analysis of the protein interactions in Saccharomyces cerevisiae
      based on several large-throughput datasets. Protein pairs resulting from gene
      duplications are used as tracers into the evolutionary past of the network. From
      this analysis, we infer rate estimates for two key evolutionary processes shaping
      the network: (i) gene duplications and (ii) gain and loss of interactions through
      mutations in existing proteins, which are referred to as link dynamics.
      Importantly, the link dynamics is asymmetric, i.e., the evolutionary steps are
      mutations in just one of the binding parters. The link turnover is shown to be
      much faster than gene duplications. Both processes are assembled into an
      empirically grounded, quantitative model for the evolution of protein interaction
      networks. CONCLUSIONS: According to this model, the link dynamics is the dominant
      evolutionary force shaping the statistical structure of the network, while the
      slower gene duplication dynamics mainly affects its size. Specifically, the model
      predicts (i) a broad distribution of the connectivities (i.e., the number of
      binding partners of a protein) and (ii) correlations between the connectivities
      of interacting proteins, a specific consequence of the asymmetry of the link
      dynamics. Both features have been observed in the protein interaction network of
      S. cerevisiae.

PMID- 15566578
TI  - Odontogenic tumors in Nigerian children and adolescents- a retrospective study of
      92 cases.
AB  - BACKGROUND: Tumours arising from odontogenic tissues are rare and constitute a
      heterogenous group of interesting lesions. The aim of this study was to determine
      the relative frequency of odontogenic tumors (OT) among Nigerian children and
      adolescents 19 years or younger. PATIENTS AND METHODS: The histopathology records
      were retrospectively reviewed for all the tumors and tumor-like lesions of the
      oral cavity and the jaws seen in children and adolescents <or= 19 years seen
      between January 1980 and December 2003. Hematoxylin and eosin-stained sections
      were re-evaluated and the diagnosis in each case was confirmed or modified
      according to World Health Organization (WHO) classification, 1992; and were
      subjected to analysis of age, sex, site of tumor and histopathologic type.
      RESULTS: A total of 477 tumors and tumor-like lesions were seen in patients <or=
      19 years during the period of the study. Of these, 92 (19.3%) were odontogenic
      tumors. Benign odontogenic tumors constituted 98.9% of the cases seen, while only
      1 case (1.1%) of malignant variety was seen during the period. The mean (SD) age
      of patients was 14.9 (+/- 3.1) years (range, 4-19 years). Male-to-female ratio
      was 1:1; and mandible-to-maxilla ratio was 2.7:1. OT's were most frequently seen
      in patients aged 16-19 years (46.7%) and the least number (2.2%) were found in
      patients aged 0-5 years. Among nine histologic types of OT seen, ameloblastoma
      (48.9%), adenomatoid odontogenic tumor (19.6%) and odontogenic myxoma (8.7%) were
      predominant. Multicystic/solid and unicystic variants of ameloblastoma were
      diagnosed in 40 (89%) and 5 (11%) cases respectively. CONCLUSIONS: Odontogenic
      tumors are relatively common in children and adolescents in Nigeria. One out of
      every 5 children and adolescents with tumors and tumor-like lesions of oral
      cavity and the jaws seen in this study had a diagnosis of odontogenic tumor.

PMID- 15566579
TI  - Combination of histopathological and electromyographic patterns can help to
      evaluate functional outcome of critical ill patients with neuromuscular weakness
      syndromes.
AB  - INTRODUCTION: The aim of the study was to describe patterns of neuromuscular
      weakness using a combination of electromyography and histology, and to evaluate
      functional outcome in patients following complicated cardiovascular surgery.
      METHODS: Fifteen adults requiring long-term mechanical ventilation (>15 days)
      following cardiovascular surgery associated with postoperative complications were
      prospectively included. Electrophysiological and histological analyses (muscle
      and nerve) were performed when failure to wean from mechanical ventilation
      associated with peripheral neuromuscular weakness was noticed. Functional
      disability was evaluated 12 months after surgery. RESULTS: Six patients had a
      predominantly axonal neuropathy, six presented with myopathy, and three patients
      had a combination of axonal neuropathy and myopathy. All of them presented with
      acute tetraparesis and failure to wean from mechanical ventilation. All of the
      study patients who received corticosteroids exhibited a myopathic pattern (with
      or without axonopathic changes) but never an axonopathic pattern only. Only two
      of the eight survivors at 12 months were not ambulatory. These two patients had
      no detectable compound muscle action potential on electrophysiological
      examination. CONCLUSION: The combination of electromyographic evaluation and
      neuromuscular histological abnormalities could help to identify the type and
      severity of neuromuscular weakness, in turn helping to evaluate the patient's
      potential functional prognosis.

PMID- 15566581
TI  - The routine use of pediatric airway exchange catheter after extubation of adult
      patients who have undergone maxillofacial or major neck surgery: a clinical
      observational study.
AB  - INTRODUCTION: We conducted the present study to determine the usefulness of
      routinely inserting a pediatric airway exchange catheter (PAEC) before tracheal
      extubation of adult patients who had undergone maxillofacial or major neck
      surgery and have risk factors for difficult reintubation. METHODS: A prospective,
      observational and clinical study was performed in the 25-bed general intensive
      care unit of a university hospital. Thirty-six adult patients who underwent
      maxillofacial or major neck surgery and had risk factors for difficult
      reintubation were extubated after insertion of the PAEC. RESULTS: Four of 36
      (11.1%) patients required emergency reintubation after 2, 4, 6 and 18 hours after
      tracheal extubation, respectively. Reintubation of these patients, which was
      thought to be nearly impossible by direct laryngoscopy, was easily achieved over
      the PAEC. CONCLUSION: The PAEC can be a life-saving device during reintubation of
      patients with risk factors for difficult reintubation such as laryngeo-pharyngeal
      oedema due to surgical manipulation or airway obstruction resulting from
      haematoma and anatomic changes. We therefore suggest the routine use of the PAEC
      in patients undergoing major maxillofacial or major neck surgery.

PMID- 15566580
TI  - Complex systems and the technology of variability analysis.
AB  - Characteristic patterns of variation over time, namely rhythms, represent a
      defining feature of complex systems, one that is synonymous with life. Despite
      the intrinsic dynamic, interdependent and nonlinear relationships of their parts,
      complex biological systems exhibit robust systemic stability. Applied to critical
      care, it is the systemic properties of the host response to a physiological
      insult that manifest as health or illness and determine outcome in our patients.
      Variability analysis provides a novel technology with which to evaluate the
      overall properties of a complex system. This review highlights the means by which
      we scientifically measure variation, including analyses of overall variation
      (time domain analysis, frequency distribution, spectral power), frequency
      contribution (spectral analysis), scale invariant (fractal) behaviour (detrended
      fluctuation and power law analysis) and regularity (approximate and multiscale
      entropy). Each technique is presented with a definition, interpretation, clinical
      application, advantages, limitations and summary of its calculation. The
      ubiquitous association between altered variability and illness is highlighted,
      followed by an analysis of how variability analysis may significantly improve
      prognostication of severity of illness and guide therapeutic intervention in
      critically ill patients.

PMID- 15566582
TI  - Early management after self-poisoning with an organophosphorus or carbamate
      pesticide - a treatment protocol for junior doctors.
AB  - Severe organophosphorus or carbamate pesticide poisoning is an important clinical
      problem in many countries of the world. Unfortunately, little clinical research
      has been performed and little evidence exists with which to determine best
      therapy. A cohort study of acute pesticide poisoned patients was established in
      Sri Lanka during 2002; so far, more than 2000 pesticide poisoned patients have
      been treated. A protocol for the early management of severely ill, unconscious
      organophosphorus/carbamate-poisoned patients was developed for use by newly
      qualified doctors. It concentrates on the early stabilisation of patients and the
      individualised administration of atropine. We present it here as a guide for
      junior doctors in rural parts of the developing world who see the majority of
      such patients and as a working model around which to base research to improve
      patient outcome. Improved management of pesticide poisoning will result in a
      reduced number of suicides globally.

PMID- 15566583
TI  - Effect of lung compliance and endotracheal tube leakage on measurement of tidal
      volume.
AB  - INTRODUCTION: The objective of this laboratory study was to measure the effect of
      decreased lung compliance and endotracheal tube (ETT) leakage on measured exhaled
      tidal volume at the airway and at the ventilator, in a research study with a test
      lung. METHODS: The subjects were infant, adult and pediatric test lungs. In the
      test lung model, lung compliances were set to normal and to levels seen in acute
      respiratory distress syndrome. Set tidal volume was 6 ml/kg across a range of
      simulated weights and ETT sizes. Data were recorded from both the ventilator
      light-emitting diode display and the CO2SMO Plus monitor display by a single
      observer. Effective tidal volume was calculated from a standard equation.
      RESULTS: In all test lung models, exhaled tidal volume measured at the airway
      decreased markedly with decreasing lung compliance, but measurement at the
      ventilator showed minimal change. In the absence of a simulated ETT leak,
      calculation of the effective tidal volume led to measurements very similar to
      exhaled tidal volume measured at the ETT. With a simulated ETT tube leak, the
      effective tidal volume markedly overestimated tidal volume measured at the
      airway. CONCLUSION: Previous investigators have emphasized the need to measure
      tidal volume at the ETT for all children. When ETT leakage is minimal, it seems
      from our simulated lung models that calculation of effective tidal volume would
      give similar readings to tidal volume measured at the airway, even in small
      patients. Future studies of tidal volume measurement accuracy in mechanically
      ventilated children should control for the degree of ETT leakage.

PMID- 15566584
TI  - The rules of the game: interprofessional collaboration on the intensive care unit
      team.
AB  - BACKGROUND: The intensive care unit (ICU) is a nexus for interspecialty and
      interdisciplinary tensions because of its pivotal role in the care of the
      hospital's most critically ill patients and in the management of critical care
      resources. In an environment charged with temporal, financial and professional
      tensions, learning how to get results collaboratively is a critical aspect of
      professional competence. This study explored how team members in the ICU interact
      to achieve daily clinical goals, delineate professional boundaries and negotiate
      complex systems issues. METHODS: Seven 1-hour focus groups were conducted with
      ICU team members in two hospitals. Participants consisted of four nursing groups
      (n = 27), two resident groups (n = 6) and one intensivist group (n = 4).
      Interviews were audio-recorded, anonymized and transcribed. With the use of a
      standard qualitative approach, transcripts were analyzed iteratively for
      recurrent themes by four researchers. RESULTS: Team members articulated their
      perceptions of the mechanisms by which team collaboration was achieved or
      undermined in a complex and high-pressure context. Two mechanisms were
      recurrently described: the perception of 'ownership' and the process of 'trade'.
      Analysis of these mechanisms reveals how power is commodified, possessed and
      exchanged as team members negotiate their daily needs and goals with one another.
      CONCLUSION: Our data provide a non-idealized depiction of how health care
      professionals function on a team so as to meet both individual and collective
      goals. We contend that the concept of 'team' must move beyond the rhetoric of
      'cooperation' and towards a more authentic depiction of the skills and strategies
      required to function in the competitive setting of the interprofessional health
      care team.

PMID- 15566585
TI  - An international sepsis survey: a study of doctors' knowledge and perception
      about sepsis.
AB  - BACKGROUND: To be able to diagnose and treat sepsis better it is important not
      only to improve the knowledge about definitions and pathophysiology, but also to
      gain more insight into specialists' perception of, and attitude towards, the
      current diagnosis and treatment of sepsis. METHODS: The study was conducted as a
      prospective, international survey by structured telephone interview. The subjects
      were intensive care physicians and other specialist physicians caring for
      intensive care unit (ICU) patients. RESULTS: The 1058 physicians who were
      interviewed (including 529 intensivists) agreed that sepsis is a leading cause of
      death on the ICU and that the incidence of sepsis is increasing, but that the
      symptoms of sepsis can easily be misattributed to other conditions. Physicians
      were concerned that this could lead to under-reporting of sepsis. Two-thirds
      (67%) were concerned that a common definition is lacking and 83% said it is
      likely that sepsis is frequently missed. Not more than 17% agreed on any one
      definition. CONCLUSION: There is a general awareness about the inadequacy of the
      current definitions of sepsis. Physicians caring for patients with sepsis
      recognise the difficulty of defining and diagnosing sepsis and are aware that
      they miss the diagnosis frequently.

PMID- 15566586
TI  - Prospective evaluation of an internet-linked handheld computer critical care
      knowledge access system.
AB  - INTRODUCTION: Critical care physicians may benefit from immediate access to
      medical reference material. We evaluated the feasibility and potential benefits
      of a handheld computer based knowledge access system linking a central academic
      intensive care unit (ICU) to multiple community-based ICUs. METHODS: Four
      community hospital ICUs with 17 physicians participated in this prospective
      interventional study. Following training in the use of an internet-linked,
      updateable handheld computer knowledge access system, the physicians used the
      handheld devices in their clinical environment for a 12-month intervention
      period. Feasibility of the system was evaluated by tracking use of the handheld
      computer and by conducting surveys and focus group discussions. Before and after
      the intervention period, participants underwent simulated patient care scenarios
      designed to evaluate the information sources they accessed, as well as the speed
      and quality of their decision making. Participants generated admission orders
      during each scenario, which were scored by blinded evaluators. RESULTS: Ten
      physicians (59%) used the system regularly, predominantly for nonmedical
      applications (median 32.8/month, interquartile range [IQR] 28.3-126.8), with
      medical software accessed less often (median 9/month, IQR 3.7-13.7). Eight out of
      13 physicians (62%) who completed the final scenarios chose to use the handheld
      computer for information access. The median time to access information on the
      handheld handheld computer was 19 s (IQR 15-40 s). This group exhibited a
      significant improvement in admission order score as compared with those who used
      other resources (P = 0.018). Benefits and barriers to use of this technology were
      identified. CONCLUSION: An updateable handheld computer system is feasible as a
      means of point-of-care access to medical reference material and may improve
      clinical decision making. However, during the study, acceptance of the system was
      variable. Improved training and new technology may overcome some of the barriers
      we identified.

PMID- 15566587
TI  - Ventilator associated pneumonia: comparison between quantitative and qualitative
      cultures of tracheal aspirates.
AB  - INTRODUCTION: Deferred or inappropriate antibiotic treatment in ventilator
      associated pneumonia (VAP) is associated with increased mortality, and clinical
      and radiological criteria are frequently employed to establish an early
      diagnosis. Culture results are used to confirm the clinical diagnosis and to
      adjust or sometimes withdraw antibiotic treatment. Tracheal aspirates have been
      shown to be useful for these purposes. Nonetheless, little is known about the
      usefulness of quantitative findings in tracheal secretions for diagnosing VAP.
      METHODS: To determine the value of quantification of bacterial colonies in
      tracheal aspirates for diagnosing VAP, we conducted a prospective follow-up study
      of 106 intensive care unit patients who were under ventilatory support. In total,
      the findings from 219 sequential weekly evaluations for VAP were examined.
      Clinical and radiological parameters were recorded and evaluated by three
      independent experts; a diagnosis of VAP required the agreement of at least two of
      the three experts. At the same time, cultures of tracheal aspirates were analyzed
      qualitatively and quantitatively (10(5) colony-forming units [cfu]/ml and 10(6)
      cfu/ml) RESULTS: Quantitative cultures of tracheal aspirates (10(5) cfu/ml and
      10(6) cfu/ml) exhibited increased specificity (48% and 78%, respectively) over
      qualitative cultures (23%), but decreased sensitivity (26% and 65%, respectively)
      as compared with the qualitative findings (81%). Quantification did not improve
      the ability to predict a diagnosis of VAP. CONCLUSION: Quantitative cultures of
      tracheal aspirates in selected critically ill patients have decreased sensitivity
      when compared with qualitative results, and they should not replace the latter to
      confirm a clinical diagnosis of VAP or to adjust antimicrobial therapy.

PMID- 15566588
TI  - Population-based epidemiology of intensive care: critical importance of
      ascertainment of residency status.
AB  - INTRODUCTION: Few studies evaluating the epidemiology of critical illness have
      used strict population-based designs that exclude subjects external to the base
      population. The objective of this study was to evaluate the potential effects of
      inclusion of nonresidents in population-based studies in intensive care. METHODS:
      A population-based cohort study including all adults admitted to Calgary Health
      Region (CHR) multidisciplinary and cardiovascular surgical intensive care units
      (ICUs) between 1 May 1999 and 30 April 2003 was conducted. A comparison of
      patients resident and nonresident in the base population was then performed.
      RESULTS: A total of 12,193 adult patients had at least one admission to an ICU;
      7767 (63.7%) were CHR residents, for an incidence of 263.7 per 100,000 per year.
      Male CHR residents were at significant increased risk for ICU admission as
      compared with females (330.5 per 100,000 versus 198.2 per 100,000; relative risk,
      1.67; 95% confidence interval, 1.59-1.74; P < 0.0001), as were CHR residents aged
      65 years and older as compared with younger patients (1719.9 per 100,000 versus
      238.7 per 100,000; relative risk, 7.21; 95% confidence interval, 6.95-7.47; P <
      0.0001). The mortality rate was significantly lower among non-CHR residents
      (12.7%) as compared with CHR residents (20.0%; P < 0.0001). Logistic regression
      modeling identified CHR residency as an independent risk factor for death (odds
      ratio, 1.4; 95% confidence interval, 1.2-1.5; P < 0.0001). CONCLUSION: This study
      provides information on the incidence of and demographic risk factors for
      admission to ICUs in a defined population. Inclusion of patients that are
      nonresident in base study populations may lead to gross errors in determination
      of the occurrence and outcomes of critical illness.

PMID- 15566589
TI  - Early postoperative hyperglycaemia is not a risk factor for infectious
      complications and prolonged in-hospital stay in patients undergoing
      oesophagectomy: a retrospective analysis of a prospective trial.
AB  - INTRODUCTION: Treating hyperglycaemia in hospitalized patients has proven to be
      beneficial, particularly in those with obstructive vascular disease. In a cohort
      of patients undergoing resection for oesophageal carcinoma (a group of patients
      with severe surgical stress but a low prevalence of vascular disease), we
      investigated whether early postoperative hyperglycaemia is associated with
      increased incidence of infectious complications and prolonged in-hospital stay.
      METHODS: Postoperative glucose values up to 48 hours after surgery were retrieved
      for 151 patients with American Society of Anesthesiologists class I or II who had
      been previously included in a randomized trial conducted in a tertiary referral
      hospital. Multivariate regression analysis was used to define the independent
      contribution of possible risk factors selected by univariate analysis. RESULTS:
      In univariate regression analysis, postoperative glucose levels were associated
      with increased length of in-hospital stay (P < 0.001) but not with infectious
      complications (P = 0.21). However, postoperative glucose concentration was not
      found to be an independent risk factor for prolonged in-hospital stay in
      multivariate analysis (P = 0.20). CONCLUSION: Our data indicate that
      postoperative hyperglycaemia is more likely to be a risk marker than a risk
      factor in patients undergoing highly invasive surgery for oesophageal cancer. We
      hypothesize that patients with a low prevalence of vascular disease may benefit
      less from intensive insulin therapy.

PMID- 15566590
TI  - G-CSF and IL-8 for early diagnosis of sepsis in neonates and critically ill
      children - safety and cost effectiveness of a new laboratory prediction model:
      study protocol of a randomized controlled trial [ISRCTN91123847].
AB  - INTRODUCTION: Bacterial infection represents a serious risk in neonates and
      critically ill paediatric patients. Current clinical practice is characterized by
      frequent antibiotic treatment despite low incidence of true infection. However,
      some patients escape early diagnosis and progress to septic shock. Many new
      markers, including cytokines, have been suggested to improve decision making, but
      the clinical efficacy of these techniques remains uncertain. Therefore, we will
      test the clinical efficacy of a previously validated diagnostic strategy to
      reduce antibiotic usage and nosocomial infection related morbidity. METHODS: All
      patients admitted to the multidisciplinary neonatal and paediatric intensive care
      unit of a university children's hospital will be included. Patients will be
      allocated either to routine sepsis work up or to the intervention strategy with
      additional cytokine measurements. Physicians will be requested to estimate the
      pre-test probability of sepsis and pneumonia at initial suspicion. In the
      treatment arm, physicians will receive raw cytokine results, the likelihood ratio
      and the updated post-test probability. A high post-test probability will suggest
      that immediate initiation of antibiotic treatment is appropriate, whereas a low
      post-test probability will be supportive of watchful waiting or discontinuing
      prophylactic empirical therapy. Physicians may overrule the suggestions resulting
      from the post-test probability. CONCLUSION: This trial will ascertain the
      clinical efficacy of introducing new diagnostic strategies consisting of pre-test
      probability estimate, novel laboratory markers, and computer-generated post-test
      probability in infectious disease work up in critically ill newborns and
      children.

PMID- 15566591
TI  - Extravascular lung water assessed by transpulmonary single thermodilution and
      postmortem gravimetry in sheep.
AB  - INTRODUCTION: Acute lung injury is associated with accumulation of extravascular
      lung water (EVLW). The aim of the present study was to compare two methods for
      quantification of EVLW: transpulmonary single thermodilution (EVLWST) and
      postmortem gravimetric (EVLWG). METHODS: Eighteen instrumented and awake sheep
      were randomly assigned to one of three groups. All groups received Ringer's
      lactate (5 ml/kg per hour intravenously). To induce lung injury of different
      severities, sheep received Escherichia coli lipopolysaccharide 15 ng/kg per min
      intravenously for 6 hours (n = 7) or oleic acid 0.06 ml/kg intravenously over 30
      min (n = 7). A third group (n = 4) was subjected to sham operation. Haemodynamic
      variables, including EVLWST, were measured using a PiCCOplus monitor (Pulsion
      Medical Systems, Munich, Germany), and the last measurement of EVLWST was
      compared with EVLWG. RESULTS: At the end of experiment, values for EVLWST (mean
      +/- standard error) were 8.9 +/- 0.6, 11.8 +/- 1.0 and 18.2 +/- 0.9 ml/kg in the
      sham-operated, lipopolysaccharide and oleic acid groups, respectively (P < 0.05).
      The corresponding values for EVLWIG were 6.2 +/- 0.3, 7.1 +/- 0.6 and 11.8 +/-
      0.7 ml/kg (P < 0.05). Ranges of EVLWIST and EVLWIG values were 7.5-21.0 and 4.9
      14.5 ml/kg. Regression analysis between in vivo EVLWST and postmortem EVLWG
      yielded the following relation: EVLWST = 1.30 x EVLWG + 2.32 (n = 18, r = 0.85, P
      < 0.0001). The mean bias +/- 2 standard deviations between EVLWST and EVLWG was
      4.9 +/- 5.1 ml/kg (P < 0.001). CONCLUSION: In sheep, EVLW determined using
      transpulmonary single thermodilution correlates closely with gravimetric
      measurements over a wide range of changes. However, transpulmonary single
      thermodilution overestimates EVLW as compared with postmortem gravimetry.

PMID- 15566592
TI  - Severe electrolyte disorders following cardiac surgery: a prospective controlled
      observational study.
AB  - INTRODUCTION: Electrolyte disorders are an important cause of ventricular and
      supraventricular arrhythmias as well as various other complications in the
      intensive care unit. Patients undergoing cardiac surgery are at risk for
      development of tachyarrhythmias, especially in the period during and immediately
      after surgical intervention. Preventing electrolyte disorders is thus an
      important goal of therapy in such patients. However, although levels of potassium
      are usually measured regularly in these patients, other electrolytes such as
      magnesium, phosphate and calcium are measured far less frequently. We
      hypothesized that patients undergoing cardiac surgical procedures might be at
      risk for electrolyte depletion, and we therefore conducted the present study to
      assess electrolyte levels in such patients. METHODS: Levels of magnesium,
      phosphate, potassium, calcium and sodium were measured in 500 consecutive
      patients undergoing various cardiac surgical procedures who required
      extracorporeal circulation (group 1). A total of 250 patients admitted to the
      intensive care unit following other major surgical procedures served as control
      individuals (group 2). Urine electrolyte excretion was measured in a subgroup of
      50 patients in both groups. RESULTS: All cardiac patients received 1 l
      cardioplegia solution containing 16 mmol potassium and 16 mmol magnesium. In
      addition, intravenous potassium supplementation was greater in cardiac surgery
      patients (mean +/- standard error: 10.2 +/- 4.8 mmol/hour in cardiac surgery
      patients versus 1.3 +/- 1.0 in control individuals; P < 0.01), and most (76%
      versus 2%; P < 0.01) received one or more doses of magnesium (on average 2.1 g)
      for clinical reasons, mostly intraoperative arrhythmia. Despite these differences
      in supplementation, electrolyte levels decreased significantly in cardiac surgery
      patients, most of whom (88% of cardiac surgery patients versus 20% of control
      individuals; P < 0.001) met criteria for clinical deficiency in one or more
      electrolytes. Electrolyte levels were as follows (mmol/l [mean +/- standard
      error]; cardiac patients versus control individuals): phosphate 0.43 +/- 0.22
      versus 0.92 +/- 0.32 (P < 0.001); magnesium 0.62 +/- 0.24 versus 0.95 +/- 0.27 (P
      < 0.001); calcium 1.96 +/- 0.41 versus 2.12 +/- 0.33 (P < 0.001); and potassium
      3.6 +/- 0.70 versus 3.9 +/- 0.63 (P < 0.01). Magnesium levels in patients who had
      not received supplementation were 0.47 +/- 0.16 mmol/l in group 1 and 0.95 +/-
      0.26 mmol/l in group 2 (P < 0.001). Urinary excretion of potassium, magnesium and
      phosphate was high in group 1 (data not shown), but this alone could not
      completely account for the observed electrolyte depletion. CONCLUSION: Patients
      undergoing cardiac surgery with extracorporeal circulation are at high risk for
      electrolyte depletion, despite supplementation of some electrolytes, such as
      potassium. The probable mechanism is a combination of increased urinary excretion
      and intracellular shift induced by a combination of extracorporeal circulation
      and decreased body temperature during surgery (hypothermia induced diuresis). Our
      findings may partly explain the high risk of tachyarrhythmia in patients who have
      undergone cardiac surgery. Prophylactic supplementation of potassium, magnesium
      and phosphate should be seriously considered in all patients undergoing cardiac
      surgical procedures, both during surgery and in the immediate postoperative
      period. Levels of these electrolytes should be monitored frequently in such
      patients.

PMID- 15566593
TI  - Discomfort and factual recollection in intensive care unit patients.
AB  - INTRODUCTION: A stay in the intensive care unit (ICU), although potentially life
      saving, may cause considerable discomfort to patients. However, retrospective
      assessment of discomfort is difficult because recollection of stressful events
      may be impaired by sedation and severe illness during the ICU stay. This study
      addresses the following questions. What is the incidence of discomfort reported
      by patients recently discharged from an ICU? What were the sources of discomfort
      reported? What was the degree of factual recollection during patients' stay in
      the ICU? Finally, was discomfort reported more often in patients with good
      factual recollection? METHODS: All ICU patients older than 18 years who had
      needed prolonged (>24 hour) admission with tracheal intubation and mechanical
      ventilation were consecutively included. Within three days after discharge from
      the ICU, a structured, in-person interview was conducted with each individual
      patient. All patients were asked to complete a questionnaire consisting of 14
      questions specifically concerning the environment of the ICU they had stayed in.
      Furthermore, they were asked whether they remembered any discomfort during their
      stay; if they did then they were asked to specify which sources of discomfort
      they could recall. A reference group of surgical ward patients, matched by sex
      and age to the ICU group, was studied to validate the questionnaire. RESULTS: A
      total of 125 patients discharged from the ICU were included in this study. Data
      for 123 ICU patients and 48 surgical ward patients were analyzed. The prevalence
      of recollection of any type of discomfort in the ICU patients was 54% (n = 66).
      These 66 patients were asked to identify the sources of discomfort, and presence
      of an endotracheal tube, hallucinations and medical activities were identified as
      such sources. The median (min-max) score for factual recollection in the ICU
      patients was 15 (0-28). The median (min-max) score for factual recollection in
      the reference group was 25 (19-28). Analysis revealed that discomfort was
      positively related to factual recollection (odds ratio 1.1; P < 0.001),
      especially discomfort caused by the presence of an endotracheal tube, medical
      activities and noise. Hallucinations were reported more often with increasing
      age. Pain as a source of discomfort was predominantly reported by younger
      patients. CONCLUSION: Among postdischarge ICU patients, 54% recalled discomfort.
      However, memory was often impaired: the median factual recollection score of ICU
      patients was significantly lower than that of matched control patients. The
      presence of an endotracheal tube, hallucinations and medical activities were most
      frequently reported as sources of discomfort. Patients with a higher factual
      recollection score were at greater risk for remembering the stressful presence of
      an endotracheal tube, medical activities and noise. Younger patients were more
      likely to report pain as a source of discomfort.

PMID- 15566594
TI  - Effects of lornoxicam on the physiology of severe sepsis.
AB  - INTRODUCTION: The purpose of the present study was to evaluate the effects of
      intravenous lornoxicam on haemodynamic and biochemical parameters, serum cytokine
      levels and patient outcomes in severe sepsis. METHODS: A total of 40 patients
      with severe sepsis were included, and were randomly assigned (20 per group) to
      receive either lornoxicam (8 mg administered intravenously every 12 hours for six
      doses) or placebo. For both groups the following were recorded: haemodynamic
      parameters (heart rate, mean arterial pressure), nasopharyngeal body temperature,
      arterial blood gas changes (pH, partial oxygen tension, partial carbon dioxide
      tension), plasma cytokine levels (IL-1beta, IL-2 receptor, IL-6, IL-8, tumour
      necrosis factor-alpha), biochemical parameters (lactate, leucocytes, trombocytes,
      creatinine, total bilirubin, serum glutamate oxalate transaminase), length of
      stay in the intensive care unit, duration of mechanical ventilation and
      mortality. All measurements were obtained at baseline (before the start of the
      study) and at 24, 48 and 72 hours from the start of lornoxicam/placebo
      administration. RESULTS: No significant differences were found between the
      intravenous lornoxicam and placebo groups in major cytokines, duration of
      ventilation and length of intensive care unit stay, and inspired fractional
      oxygen/arterial oxygen tension ratio (P > 0.05). CONCLUSION: In these patients
      with severe sepsis, we found intravenous lornoxicam to exert no effect on
      haemodynamic and biochemical parameters, cytokine levels, or patient outcomes.
      Because of the small number of patients included in the study and the short
      period of observation, these findings require confirmation by larger clinical
      trials of intravenous lornoxicam, administered in a dose titrated manner.

PMID- 15566595
TI  - The effect of interruption to propofol sedation on auditory event-related
      potentials and electroencephalogram in intensive care patients.
AB  - INTRODUCTION: In this observational pilot study we evaluated the
      electroencephalogram (EEG) and auditory event-related potentials (ERPs) before
      and after discontinuation of propofol sedation in neurologically intact intensive
      care patients. METHODS: Nineteen intensive care unit patients received a propofol
      infusion in accordance with a sedation protocol. The EEG signal and the ERPs were
      measured at the frontal region (Fz) and central region (Cz), both during propofol
      sedation and after cessation of infusion when the sedative effects had subsided.
      The EEG signal was subjected to power spectral estimation, and the total root
      mean squared power and spectral edge frequency 95% were computed. For ERPs, we
      used an oddball paradigm to obtain the N100 and the mismatch negativity
      components. RESULTS: Despite considerable individual variability, the root mean
      squared power at Cz and Fz (P = 0.004 and P = 0.005, respectively) and the
      amplitude of the N100 component in response to the standard stimulus at Fz (P =
      0.022) increased significantly after interruption to sedation. The amplitude of
      the N100 component (at Cz and Fz) was the only parameter that differed between
      sedation levels during propofol sedation (deep versus moderate versus light
      sedation: P = 0.016 and P = 0.008 for Cz and Fz, respectively). None of the
      computed parameters correlated with duration of propofol infusion. CONCLUSION:
      Our findings suggest that use of ERPs, especially the N100 potential, may help to
      differentiate between levels of sedation. Thus, they may represent a useful
      complement to clinical sedation scales in the monitoring of sedation status over
      time in a heterogeneous group of neurologically intact intensive care patients.

PMID- 15566596
TI  - Case report: greater meningeal inflammation in lumbar than in ventricular region
      in human bacterial meningitis.
AB  - Differences in the composition of ventricular and lumbar cerebrospinal fluid
      (CSF) based on single pairs of samples have previously been described. We
      describe a patient that developed post-surgical recurrent meningitis monitored by
      daily biochemical and bacteriological CSF analysis, simultaneously withdrawn from
      lumbar space and ventricles. A 20-year-old Caucasian man was admitted to the ICU
      after a resection of a chordoma that extended from the sphenoidal sinus to the
      anterior face of C2. CSF was continuously leaking into the pharyngeal cavity
      after surgery, and three episodes of recurrent meningitis, all due to Pseudomonas
      aeruginosa O12, occurred. Our case showed permanent ventricular-to-lumbar CSF
      gradients of leukocytes, protein and glucose that were increased during the acute
      phase of meningitis, with the greatest amplitude being observed when bacteria
      were present in both ventricular and lumbar CSF. This might suggest a greater
      extent of meningeal inflammation in the lumbar than in the ventricular region.
      Our case also showed that the increase in intravenous antibiotics (cefepim from 8
      to 12 g/day and ciprofloxacine from 1.2 to 2.4 g/day) led to an increase in
      concentration in plasma but not in CSF.

PMID- 15566597
TI  - Cardiovascular stability during arteriovenous extracorporeal therapy: a
      randomized controlled study in lambs with acute lung injury.
AB  - INTRODUCTION: Clinical application of arteriovenous (AV) extracorporeal membrane
      oxygenation (ECMO) requires assessment of cardiovascular ability to respond
      adequately to the presence of an AV shunt in the face of acute lung injury (ALI).
      This ability may be age dependent and vary with the experimental model. We
      studied cardiovascular stability in a lamb model of severe ALI, comparing
      conventional mechanical ventilation (CMV) with AV-ECMO therapy. METHODS:
      Seventeen lambs were anesthetized, tracheotomized, paralyzed, and ventilated to
      maintain normocapnia. Femoral and jugular veins, and femoral and carotid arteries
      were instrumented for the AV-ECMO circuit, systemic and pulmonary artery blood
      pressure monitoring, gas exchange, and cardiac output determination
      (thermodilution technique). A severe ALI (arterial oxygen tension/inspired
      fractional oxygen <200) was induced by lung lavage (repeated three times, each
      with 5 ml/kg saline) followed by tracheal instillation of 2.5 ml/kg of 0.1 N HCl.
      Lambs were consecutively assigned to CMV treatment (n = 8) or CMV plus AV-ECMO
      therapy using up to 15% of the cardiac output for the AV shunt flow during a 6
      hour study period (n = 9). The outcome measures were the degree of inotropic and
      ventilator support needed to maintain hemodynamic stability and normocapnia,
      respectively. RESULTS: Five of the nine lambs subjected to AV-ECMO therapy (56%)
      died before completion of the 6-hour study period, as compared with two out of
      eight lambs (25%) in the CMV group (P > 0.05; Fisher's exact test). Surviving and
      nonsurviving lambs in the AV-ECMO group, unlike the CMV group, required
      continuous volume expansion and inotropic support (P < 0.001; Fisher's exact
      test). Lambs in the AV-ECMO group were able to maintain normocapnia with a
      maximum of 30% reduction in the minute ventilation, as compared with the CMV
      group (P < 0.05). CONCLUSION: AV-ECMO therapy in lambs subjected to severe ALI
      requires continuous hemodynamic support to maintain cardiovascular stability and
      normocapnia, as compared with lambs receiving CMV support.

PMID- 15566598
TI  - Perioperative factors determine outcome after surgery for severe acute
      pancreatitis.
AB  - INTRODUCTION: There is evidence that postponing surgery in critically ill
      patients with severe acute pancreatitis (SAP) leads to improved survival, but
      previous reports included patients with both sterile and infected pancreatic
      necrosis who were operated on for various indications and with different degrees
      of organ dysfunction at the moment of surgery, which might be an important bias.
      The objective of this study is to analyze the impact of timing of surgery and
      perioperative factors (severity of organ dysfunction and microbiological status
      of the necrosis) on mortality in intensive care unit (ICU) patients undergoing
      surgery for SAP. METHODS: We retrospectively (January 1994 to March 2003)
      analyzed patients admitted to the ICU with SAP. Of 124 patients, 56 were treated
      surgically; these are the subject of this analysis. We recorded demographic
      characteristics and predictors of mortality at admission, timing of and
      indications for surgery, and outcome. We also studied the microbiological status
      of the necrosis and organ dysfunction at the moment of surgery. RESULTS:
      Patients' characteristics were comparable in patients undergoing early and late
      surgery, and there was a trend toward a higher mortality in patients who
      underwent early surgery (55% versus 29%, P = 0.06). In univariate analysis,
      patients who died were older, had higher organ dysfunction scores at the day of
      surgery, and had sterile necrosis more often; there was a trend toward earlier
      surgery in these patients. Logistic regression analysis showed that only age,
      organ dysfunction at the moment of surgery, and the presence of sterile necrosis
      were independent predictors of mortality. CONCLUSIONS: In this cohort of
      critically ill patients operated on for SAP, there was a trend toward higher
      mortality in patients operated on early in the course of the disease, but in
      multivariate analysis, only greater age, severity of organ dysfunction at the
      moment of surgery, and the presence of sterile necrosis, but not the timing of
      the surgical intervention, were independently associated with an increased risk
      for mortality.

PMID- 15566599
TI  - Evidence-based medicine journal club.

PMID- 15566600
TI  - Monitoring and oversight in critical care research.
AB  - Institutionally based research ethics review is a form of peer review that has -
      for better or worse - become the norm throughout the world. The vast majority of
      research ethics review takes the form of protocol review alone, conducted in
      advance of the research. Although oversight and monitoring in clinical research
      have long been recognized as essential features of sound research ethics, they
      are seldom exercised in ways that fulfill their motivating goals: to ensure that
      research is conducted as planned; that research participants comprehend the
      information presented to them in the consent process; and that the potential
      benefits and risks of study participation remain acceptable. Annual review of
      continuing research, monitoring informed consent, monitoring adherence to
      approved protocols and monitoring integrity of research data comprise the main
      types of monitoring and oversight activity. We believe that our institutionally
      based systems of research ethics review and responsibility require greater
      engagement and participation from researchers and research administrators. The
      appropriate role of critical care researchers and research administrators is to
      provide leadership to move toward a greater recognition of the importance of
      monitoring and oversight for ethical and high quality clinical research.

PMID- 15566601
TI  - Of hemorrhagic shock, spherical cows and Aloe vera.
AB  - The central question explored in this commentary is whether the beneficial
      effects of an Aloe vera derived drag-reducing polymer during hemorrhagic shock is
      due to its O2 radical scavenging properties or to changes in blood rheology.

PMID- 15566602
TI  - Recently published papers: clunk-click every trip, smile, but don't stop for a
      drink on the way.
AB  - Reviews of the risks associated with intrahospital transfer and prolonged spinal
      immobilization made uncomfortable reading in August. Studies on the timing of
      tracheotomy and a potential role for exogenous surfactant will have done little
      to allay controversy. We are reminded of the neutrality of the Swiss, and gain
      valuable insight into prognostic tools in mechanically ventilated patients with
      cirrhotic liver disease.

PMID- 15566603
TI  - Genetic epidemiology of acute lung injury: choosing the right candidate genes is
      the first step.
AB  - In an innovative scientific review in this issue, Grigoryev and colleagues report
      a method for choosing candidate genes for acute lung injury (ALI) based on gene
      expression data derived from multiple animal models of mechanical ventilation and
      shear stress. The authors conclude there are five key biologic processes that
      warrant further investigation: inflammatory and immune responses, cell
      proliferation, chemotaxis, and blood coagulation. This review represents an
      important first step toward studying the genetic epidemiology of ventilator
      induced lung injury and ALI. The application of these findings to future human
      studies of the genetic influence on ALI risks and outcomes is discussed here.

PMID- 15566604
TI  - Variability science in intensive care - how relevant is it?
AB  - The article by Seely et al. in this issue of Critical Care highlights that
      variability portend prognosis. Numerous parameters interact to modify variability
      in intensive care. The commentary discusses why variability can nevertheless
      accurately estimate prognosis and how easily this can be implemented in the
      critically ill.

PMID- 15566605
TI  - A stronger approach to weakness in the intensive care unit.
AB  - ICU-acquired limb and respiratory muscle weakness is a common, serious ICU
      syndrome, increasing in frequency with prolonged ICU stay and sepsis. A
      systematic approach facilitates precise localization of the problem within
      central or peripheral nervous system. Most cases relate to critical illness
      polyneuropathy or myopathy or a combination of both (critical illness
      neuromyopathy). Within the latter entity, the relative contribution of neuropathy
      versus myopathy varies considerably among affected patients. Muscle enzyme
      testing, electromyography-nerve conduction and muscle biopsy are valuable
      investigative tests. Nerve biopsy is less commonly needed, but is useful when
      vascultis is suspected.

PMID- 15566606
TI  - Shockingly complex: the difficult road to introducing new ideas to critical care.
AB  - Resuscitation of critically ill patients with trauma or sepsis continues to
      challenge clinicians. Early imperatives include diagnostic judgment as to the
      presenting problem - sepsis or trauma. Subsequently, the clinician decides on the
      phase of resuscitation required for support - 'ebb' versus 'flow'. Finally, the
      clinician needs to determine what therapeutic strategies to employ and then judge
      when resuscitation is complete. Shortcomings of current approaches to determining
      the adequacy of circulatory resuscitation have prompted the evaluation of new
      technologies purported to directly assess microcirculatory flow as a clinical
      endpoint for the adequacy of resuscitation. While early studies are intriguing,
      this technology requires much more study before it can be considered for
      widespread adoption by the clinician.

PMID- 15566607
TI  - Attending to the lightness of numbers: toward the understanding of critical care
      epidemiology.
AB  - Most of the epidemiological studies in critical care do not express their results
      in terms of population burden of critical illness. This happens because the
      population at risk of critical illness is particularly difficult to estimate,
      once intensive care units (ICUs) receive patients from many sources. The study by
      Laupland in this issue of Critical Care provides a good estimate of the incidence
      of admission to ICUs in the Calgary Health Region. He considered the Calgary
      Health Region population as the denominator and explored the effects of a
      changing numerator according to the residency status (resident in Calgary or not)
      on the estimation of the burden of admission to the ICU. He demonstrated that if
      the residency status were not known, the incidence of admission to the ICU would
      have been overestimated by more than 50%. Furthermore, non-residents had a lower
      mortality despite higher Acute Physiology and Chronic Health Evaluation (APACHE)
      II and Therapeutic Intervention Scoring System (TISS) scores. There is tremendous
      variability in decisions to admit a patient to the ICU and the epidemiology of
      critical care is influenced by them in a subtle but inextricable way. An
      understanding of the population epidemiology of critical illness and the use of
      the ICU, the variations in these parameters, and factors that influence this
      variation is extremely important. The notable effect of a changing numerator on
      the estimation of the population burden of ICU admissions in the study by
      Laupland illustrates how fluid our estimates of disease incidence and mortality -
      the mainstays of epidemiology - can be.

PMID- 15566608
TI  - Qualitative cultures in ventilator-associated pneumonia - can they be used with
      confidence?
AB  - The sensitivity and specificity of the radiographic and clinical evidence used to
      diagnose ventilator-associated pneumonia vary depending on the number of clinical
      criteria present. Bacteriological confirmation that rules out other diseases can
      be achieved by quantitative or qualitative cultures of tracheal aspirate. The
      rate of tracheal colonization in ventilated patients reduces the usefulness of
      qualitative cultures, but the absence of multiresistant micro-organisms in
      cultures from patients on prior antibiotics or a sterile culture in patients
      without prior antimicrobials may provide sufficient justification to stop or de
      escalate antibiotics. However, more accurate guidance regarding whether
      antibiotics are unnecessary and should be stopped is provided by quantitative
      culture.

PMID- 15566609
TI  - Tight blood glucose control: a recommendation applicable to any critically ill
      patient?
AB  - The issue of tight glucose control with intensive insulin therapy in critically
      ill patients remains controversial. Although compelling evidence supports this
      strategy in postoperative patients who have undergone cardiac surgery, the use of
      tight glucose control has been challenged in other situations, including in
      medical critically ill patients and in those who have undergone non-cardiac
      surgery. Similarly, the mechanisms that underlie the effects of high-dose insulin
      are not fully elucidated. These arguments emphasize the need to study the effects
      of tight glucose control in a large heterogeneous cohort of intensive care unit
      patients.

PMID- 15566610
TI  - Risk management in patients with severe acute pancreatitis.
AB  - Primary or secondary infection of necrotized areas by enteral bacteria is
      considered a primary cause of mortality in patients with severe acute
      pancreatitis (SAP). Indeed, 20-30% of patients die during the course of the
      disease from multiple organ dysfunction after infection. This is why strategies
      such as antibiotic prophylaxis and early surgical intervention are appealing, but
      the controlled data that support these measures are insufficient. On the other
      hand, environmental risk factors (e.g. smoking, alcohol) and genetic
      predisposition have been identified; together, these led to SAP being considered
      a 'multifactorial' disease. However, this description does not help the
      intensivist to assess risk in the individual patient. A number of prognostic
      factors in SAP have been identified, and different scoring systems have been
      developed that include therapy-associated and patient-related factors.
      Nevertheless, at present no prognostic model is available that takes into account
      all of these predictors. Moreover, despite several attempts to create guideline
      based strategies, SAP is still characterized by rapidly progressive multiple
      organ failure and high mortality, and both surgical and conservative therapies
      yield poor outcomes. This brief commentary highlights the most recent
      developments in risk management for patients with SAP.

PMID- 15566611
TI  - Optimum sedation and analgesia in critical illness: we need to keep trying.
AB  - Many studies have documented patients' distressing recollections of the intensive
      care unit (ICU). The study by van de Leur and colleagues, conducted in a group of
      surgical ICU patients with moderate severity of sickness, found that the
      frequency of such unpleasant memories was increased in those able to recall
      factual information about their stay in the ICU. The study did not include
      sedation scoring but it did use a simple tool to assess factual recall. This tool
      appeared reliable and could be easily applied in any ICU. Previous work strongly
      suggests that abolishing memory of ICU by using deep sedation would not be an
      appropriate response to these findings. Rather, we need to work on strategies
      that reduce distress by improving analgesia, reducing noxious stimuli (if
      possible) and, potentially, using pharmacology to produce a calm patient with
      minimal sedation. Achieving the latter is rarely possible today but it might
      become possible with future drug development.

PMID- 15566612
TI  - The challenge of sepsis.

PMID- 15566613
TI  - Can electrophysiological assessments of brain function be useful to the intensive
      care physician in daily clinical practice?
AB  - Changes in electroencephalogram parameters and auditory event-related potentials,
      induced by interruption to propofol sedation in intensive care patients, provide
      a number of electrophysiological measures that can be used to assess neurological
      function accurately. Studies of electroencephalogram parameters suggest that
      power spectral estimation, as root mean square power, is more useful and precise
      than spectral edge frequency 95% in evaluating the functional integrity of the
      brain. When such parameters are used to evaluate neurological function, in
      particular the N100 and mismatch negativity components, a precise assessment of a
      patient's readiness to awaken from a pharmacologically induced coma (such as
      sedation) can be obtained. In terms of ease of use, however, it is more difficult
      to establish whether N100 or mismatch negativity is superior.

PMID- 15566614
TI  - Science review: searching for gene candidates in acute lung injury.
AB  - Acute lung injury (ALI) is a complex and devastating illness, often occurring
      within the setting of sepsis, and carries an annual mortality rate of 30-50%.
      Although the genetic basis of ALI has not been fully established, an increasing
      body of evidence suggests that genetic predisposition contributes to disease
      susceptibility and severity. Significant difficulty exists, however, in defining
      the exact nature of these genetic factors, including large phenotypic variance,
      incomplete penetrance, complex gene-environment interactions, and strong
      potential for locus heterogeneity. We utilized the candidate gene approach and an
      ortholog gene database to provide relevant gene ontologies and insights into the
      genetic basis of ALI. We employed a Medline search of selected basic and clinical
      studies in the English literature and studies sponsored by the HopGene National
      Institutes of Health sponsored Program in Genomic Applications. Extensive gene
      expression profiling studies in animal models of ALI (rat, murine, canine), as
      well as in humans, were performed to identify potential candidate genes
      http://www.hopkins-genomics.org/. We identified a number of candidate genes for
      ALI, with blood coagulation and inflammation gene ontologies being the most
      highly represented. The candidate gene approach coupled with extensive gene
      profiling and novel bioinformatics approaches is a valuable way to identify genes
      that are involved in ALI.

PMID- 15566615
TI  - Science review: quantitative acid-base physiology using the Stewart model.
AB  - There has been renewed interest in quantifying acid-base disorders in the
      intensive care unit. One of the methods that has become increasingly used to
      calculate acid-base balance is the Stewart model. This model is briefly discussed
      in terms of its origin, its relationship to other methods such as the base excess
      approach, and the information it provides for the assessment and treatment of
      acid-base disorders in critically ill patients.

PMID- 15566616
TI  - Bench-to-bedside review: acute respiratory distress syndrome - how neutrophils
      migrate into the lung.
AB  - Acute lung injury and its more severe form, acute respiratory distress syndrome,
      are major challenges in critically ill patients. Activation of circulating
      neutrophils and transmigration into the alveolar airspace are associated with
      development of acute lung injury, and inhibitors of neutrophil recruitment
      attenuate lung damage in many experimental models. The molecular mechanisms of
      neutrophil recruitment in the lung differ fundamentally from those in other
      tissues. Distinct signals appear to regulate neutrophil passage from the
      intravascular into the interstitial and alveolar compartments. Entry into the
      alveolar compartment is under the control of CXC chemokine receptor (CXCR)2 and
      its ligands (CXC chemokine ligand [CXCL]1-8). The mechanisms that govern
      neutrophil sequestration into the vascular compartment of the lung involve
      changes in the actin cytoskeleton and adhesion molecules, including selectins,
      beta2 integrins and intercellular adhesion molecule-1. The mechanisms of
      neutrophil entry into the lung interstitial space are currently unknown. This
      review summarizes mechanisms of neutrophil trafficking in the inflamed lung and
      their relevance to lung injury.

PMID- 15566617
TI  - Bench-to-bedside review: sepsis is a disease of the microcirculation.
AB  - Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that
      maintaining systemic blood pressure is associated with inadequate perfusion of
      the microcirculation in sepsis. Microcirculatory perfusion is regulated by an
      intricate interplay of many neuroendocrine and paracrine pathways, which makes
      blood flow though this microvascular network a heterogeneous process. Owing to an
      increased microcirculatory resistance, a maldistribution of blood flow occurs
      with a decreased systemic vascular resistance due to shunting phenomena. Therapy
      in shock is aimed at the optimization of cardiac function, arterial hemoglobin
      saturation and tissue perfusion. This will mean the correction of hypovolemia and
      the restoration of an evenly distributed microcirculatory flow and adequate
      oxygen transport. A practical clinical score for the definition of shock is
      proposed and a novel technique for bedside visualization of the capillary network
      is discussed, including its possible implications for the treatment of septic
      shock patients with vasodilators to open the microcirculation.

PMID- 15566618
TI  - Bench-to-bedside review: the role of the alveolar epithelium in the resolution of
      pulmonary edema in acute lung injury.
AB  - Clearance of pulmonary edema fluid is accomplished by active ion transport,
      predominantly by the alveolar epithelium. Various ion pumps and channels on the
      surface of the alveolar epithelial cell generate an osmotic gradient across the
      epithelium, which in turn drives the movement of water out of the airspaces.
      Here, the mechanisms of alveolar ion and fluid clearance are reviewed. In
      addition, many factors that regulate the rate of edema clearance, such as
      catecholamines, steroids, cytokines, and growth factors, are discussed. Finally,
      we address the changes to the alveolar epithelium and its transport processes
      during acute lung injury (ALI). Since relevant clinical outcomes correlate with
      rates of edema clearance in ALI, therapies based on our understanding of the
      mechanisms and regulation of fluid transport may be developed.

PMID- 15566619
TI  - Clinical review: vascular access for fluid infusion in children.
AB  - The current literature on venous access in infants and children for acute
      intravascular access in the routine situation and in emergency or intensive care
      settings is reviewed. The various techniques for facilitating venous cannulation,
      such as application of local warmth, transillumination techniques and epidermal
      nitroglycerine, are described. Preferred sites for central venous access in
      infants and children are the external and internal jugular veins, the subclavian
      and axillary veins, and the femoral vein. The femoral venous cannulation appears
      to be the most safe and reliable technique in children of all ages, with a high
      success and low complication rates. Evidence from the reviewed literature
      strongly supports the use of real-time ultrasound techniques for venous
      cannulation in infants and children. Additionally, in emergency situations the
      intraosseous access has almost completely replaced saphenous cutdown procedures
      in children and has decreased the need for immediate central venous access.

PMID- 15566620
TI  - Clinical review: immunomodulatory effects of dopamine in general inflammation.
AB  - Large quantitaties of inflammatory mediators are released during the course of
      endotoxaemia. These mediators in turn can stimulate the sympathetic nervous
      system (SNS) to release catecholamines, which ultimately regulate inflammation
      associated impairment in tissue perfusion, myocardial impairment and
      vasodilatation. Treatment of sepsis is based on surgical and/or antibiotic
      therapy, appropriate fluid management and application of vasoactive
      catecholamines. With respect to the latter, discussions on the vasopressor of
      choice are still ongoing. Over the past decade dopamine has been considered the
      'first line' vasopressor and is frequently used to improve organ perfusion and
      blood pressure. However, there is a growing body of evidence that dopamine has
      deleterious side effects; therefore, its clinical relevance seems to be more and
      more questionable. Nevertheless, it has not been convincingly demonstrated that
      other catecholamines are superior to dopamine in this respect. Apart from its
      haemodynamic action, dopamine can modulate immune responses by influencing the
      cytokine network. This leads to inhibition of expression of adhesion molecules,
      inhibition of cytokine and chemokine production, inhibition of neutrophil
      chemotaxis and disturbed T-cell proliferation. In the present review we summarize
      our knowledge of the immunomodulatory effects of dopamine, with an emphasis on
      the mechanisms by which these effects are mediated.

PMID- 15566621
TI  - Clinical review: biphasic positive airway pressure and airway pressure release
      ventilation.
AB  - This review focuses on mechanical ventilation strategies that allow unsupported
      spontaneous breathing activity in any phase of the ventilatory cycle. By allowing
      patients with the acute respiratory distress syndrome to breathe spontaneously,
      one can expect improvements in gas exchange and systemic blood flow, based on
      findings from both experimental and clinical trials. In addition, by increasing
      end-expiratory lung volume, as occurs when using biphasic positive airway
      pressure or airway pressure release ventilation, recruitment of collapsed or
      consolidated lung is likely to occur, especially in juxtadiaphragmatic lung
      legions. Traditional approaches to mechanical ventilatory support of patients
      with acute respiratory distress syndrome require adaptation of the patient to the
      mechanical ventilator using heavy sedation and even muscle relaxation. Recent
      investigations have questioned the utility of sedation, muscle paralysis and
      mechanical control of ventilation. Furthermore, evidence exists that lowering
      sedation levels will decrease the duration of mechanical ventilatory support,
      length of stay in the intensive care unit, and overall costs of hospitalization.
      Based on currently available data, we suggest considering the use of techniques
      of mechanical ventilatory support that maintain, rather than suppress,
      spontaneous ventilatory effort, especially in patients with severe pulmonary
      dysfunction.

PMID- 15566622
TI  - Clinical review: impact of emergency department care on intensive care unit
      costs.
AB  - Critical care is both expensive and increasing. Emergency department (ED)
      management of critically ill patients before intensive care unit (ICU) admission
      is an under-explored area of potential cost saving in the ICU. Although limited,
      current data suggest that ED care has a significant impact on ICU costs both
      positive and negative. ICU practices can also affect the ED, with a lack of ICU
      beds being the primary reason for ED overcrowding and ambulance diversion in the
      USA. Earlier application in the ED of intensive therapies such as goal-directed
      therapy and noninvasive ventilation may reduce ICU costs by decreasing length of
      stay and need for admission. Future critical care policies and health services
      research should include both the ED and ICU in their analyses.

PMID- 15566623
TI  - Clinical review: how to optimize management of high-risk surgical patients.
AB  - For many patients optimal perioperative care may require little or no additional
      medical management beyond that given by the anaesthetist and surgeon. However,
      the continued existence of a group of surgical patients at high risk for
      morbidity and mortality indicates an ongoing need to identify such patients and
      deliver optimal care throughout the perioperative period. A group of patients
      exists in whom the risk for death and serious complications after major surgery
      is in excess of 20%. The risk is related mainly to the patient's preoperative
      physiological condition and, in particular, the cardiovascular and respiratory
      reserves. Cardiovascular management of the high-risk surgical patient is of
      particular importance. Once the medical management of underlying disease has been
      optimized, two principal areas remain: the use of haemodynamic goals to guide
      fluid and inotropic therapy, and perioperative beta blockade. A number of studies
      have shown that the use of goal-directed haemodynamic therapy during the
      perioperative period can result in large reductions in morbidity and mortality.
      Some patients may also benefit from perioperative beta blockade, which in
      selected patients has also been shown to result in significant mortality
      reductions. In this review a pragmatic approach to perioperative management is
      described, giving guidance on the identification of the high-risk patient and on
      the use of goal-directed haemodynamic therapy and beta blockade.

PMID- 15566624
TI  - Statistics review 13: receiver operating characteristic curves.
AB  - This review introduces some commonly used methods for assessing the performance
      of a diagnostic test. The sensitivity, specificity and likelihood ratio of a test
      are discussed. The uses of the receiver operating characteristic curve and the
      area under the curve are explained.

PMID- 15566625
TI  - An adaptogenic role for omega-3 fatty acids in stress; a randomised placebo
      controlled double blind intervention study (pilot) [ISRCTN22569553].
AB  - BACKGROUND: There is evidence for an adaptive role of the omega -3 fatty acid,
      docosahexaenoic acid (DHA) during stress. Mechanisms of action may involve
      regulation of stress mediators, such as the catecholamines and proinflammatory
      cytokines. Prevention of stress-induced aggression and hostility were
      demonstrated in a series of clinical trials. This study investigates whether
      perceived stress is ameliorated by DHA in stressed university staff. METHODS:
      Subjects that scored > or = 17 on the Perceived Stress Scale were randomised into
      a 6-week pilot intervention study. The diet reactive group was supplemented with
      6 g of fish oil containing 1.5 g per day DHA, while the placebo group was
      supplemented with 6 g a day of olive oil. The groups were compared with each
      other and a wider cross sectional study population that did not receive either
      active or placebo intervention. RESULTS: There was a significant reduction in
      perceived stress in both the fish oil and the placebo group from baseline. There
      was also a significant between-group difference between the fish oil group and
      the no-treatment controls in the rate of stress reduction (p < 0.05). However,
      there was not a significant between-group difference between the fish oil and the
      placebo group, nor the placebo group and the control group. These results are
      discussed in the context of several methodological limitations. The significant
      stress reductions in both the fish oil and the placebo group are considered in
      view of statistical regression, an effect likely to have been exaggerated by the
      time course of the study, a large placebo effect and the possibility of an active
      effect from the placebo. CONCLUSION: There were significant differences (p <
      0.05) in the fish oil group compared with no-treatment controls. This effect was
      not demonstrated in the placebo group. As a pilot study, it was not sufficiently
      powered to find the difference between the fish oil group and the placebo group
      significant. Further work needs to be undertaken to conclusively demonstrate
      these data trends. However, the findings from this research support the
      literature in finding a protective or 'adaptogenic' role for omega-3 fatty acids
      in stress.

PMID- 15566626
TI  - Autodissemination of the entomopathogenic fungus Metarhizium anisopliae amongst
      adults of the malaria vector Anopheles gambiae s.s.
AB  - BACKGROUND: The entomopathogenic fungus Metarhizium anisopliae is being
      considered as a biocontrol agent for adult African malaria vectors. In the
      laboratory, work was carried out to assess whether horizontal transmission of the
      pathogen can take place during copulation, as this would enhance the impact of
      the fungus on target populations when compared with insecticides. METHODS: Virgin
      female Anopheles gambiae sensu stricto were exposed to conidia whilst resting on
      fungus-impregnated paper. These females were then placed together for one hour
      with uncontaminated males in proportions of either 1:1 or 1:10 shortly before the
      onset of mating activity. RESULTS: Males that had acquired fungal infection after
      mating indicate that passive transfer of the pathogen from infected females does
      occur, with mean male infection rates between 10.7 +/- 3.2% and 33.3 +/- 3.8%.
      The infections caused by horizontal transmission did not result in overall
      differences in survival between males from test and control groups, but in one of
      the three experiments the infected males had significantly shorter life spans
      than uninfected males (P < 0.05). CONCLUSION: This study shows that
      autodissemination of fungal inoculum between An. gambiae s.s. mosquitoes during
      mating activity is possible under laboratory conditions. Field studies are
      required next, to assess the extent to which this phenomenon may augment the
      primary contamination pathway (i.e. direct contact with fungus-impregnated
      targets) of vector populations in the field.

PMID- 15566627
TI  - Relationship between three palliative care outcome scales.
AB  - BACKGROUND: Various scales have been used to assess palliative outcomes. But
      measurement can still be problematic and core components of measures have not
      been identified. This study aimed to determine the relationships between, and
      factorial structure of, three widely used scales among advanced cancer patients.
      METHODS: Patients were recruited who received home or hospital palliative care
      services in the south of England. Hope, quality of life and palliative outcomes
      were assessed by patients in face to face interviews, using three previously
      established scales - a generic measure (EQoL), a palliative care specific measure
      (POS) and a measure of hope (Herth Hope Index). Analysis comprised: exploratory
      factor analysis of each individual scale, and all scales combined, and
      confirmatory factor analysis for model building and validation. RESULTS: Of 171
      patients identified, 140 (81%) consented and completed first interviews; mean age
      was 71 years, 54% were women, 132 had cancer. In exploratory analysis of
      individual means, three out of the five factors in the EQoL explained 75% of its
      variability, four out of the 10 factors in POS explained 63% of its variability,
      and in the Hope Index, nine out of the 12 items explained 69% of its variability.
      When exploring the relative factorial structure of all three scales, five factors
      explained 56% of total combined variability. Confirmatory analysis reduced this
      to a model with four factors - self-sufficiency, positivity, symptoms and
      spiritual. Removal of the spiritual factor left a model with an improved goodness
      of fit and a measure with 11 items. CONCLUSION: We identified three factors which
      are important outcomes and would be simple to measure in clinical practice and
      research.

PMID- 15566637
TI  - [Effect of EBV encoded BARF1 gene on malignant transformation of human epithelial
      cell line HBE].
AB  - BACKGROUND & OBJECTIVE: The BARF(1) (BamHI A right frame1)gene,encoded by Epstein
      Barr virus(EBV),may have oncogenic properties,which leaded to immortalization of
      a monkey kidney epithelial cell line and malignant transformation of human B
      lymphocytes and murine fibroblasts. This study was designed to evaluate effect of
      BARF(1) on cell transformation and tumorgenesis on human epithelia and its
      mechanisms. METHODS: BARF(1) was amplified from B95-8 cell line by polymerase
      chain reaction (PCR). Eukaryotic recombinant vector pcDNA(3)-BARF(1) was
      constructed,and transfected into human bronchial epithelial cell line HBE,and
      expression of BARF(1) in the transfected cells was detected by Western blot.
      Growth status,proliferation rate,ability of colony formation in soft agar,and
      tumorigenicity of HBE cells transfected with BARF(1) were studied. RESULTS:
      BARF(1) gene promoted proliferation and transformation of HBE cells. After
      injected with 1 x 10(7) HBE cells transfected with BARF(1),tumor nodes were
      observed in 2 of 6 mice at the 10th day. CONCLUSION: BARF(1),as a virus
      oncogene,may play an important role in malignant transformation of HBE cells.

PMID- 15566638
TI  - [Effect of epidermal growth factor receptor-selective tyrosine kinase inhibitor
      gefitinib on nasopharyngeal carcinoma xenografts].
AB  - BACKGROUND & OBJECTIVE: Gefitinib,an anilinoquinazoline,is an orally
      active,selective epidermal growth factor receptor(EGFR) tyrosine kinase
      inhibitor,which has been approved for the treatment of advanced non-small cell
      lung cancer. We have found that the proliferation of nasopharyngeal carcinoma
      (NPC) cell lines CNE1,CNE2,and SUNE1 was inhibited by Gefitinib. The present
      study was designed to evaluate the effect of Gefitinib alone or in combination
      with cisplatin (DDP) on NPC CNE2 xenografts. METHODS: Exponentially growing CNE2
      cells were prepared into cell suspension (1 x 10(7) cells/ml). Suspension of 200
      mul of CNE2 cells was injected s.c. into the right flank area of the mice. After
      7 days,when well-established tumors of 100-200 mm(3) were detected,mice were
      randomized into five groups: control group,Gefitinib (100 mg/kg) group,Gefitinib
      (200 mg/kg) group,DDP group,and Gefitinib (100 mg/kg) plus DDP group. Gefitinib
      was administered by oral gavage on days 1-5 of each week for 4 weeks. DDP was
      administered i.p. once a week for 4 weeks. Tumor volume was determined by direct
      measurement with caliper and calculated by the formula 1/2x(large
      diameter)x(small diameter)(2). The mice were sacrificed at two days after the
      treatment ended; tumor masses were removed and weighed. The tumor inhibition
      rates were calculated. The student's test was used to evaluated the statistical
      significance of the results. RESULTS: Growth curves showed that tumor masses of
      control group grew more rapidly than ones of every treatment group. The average
      tumor volume was significantly smaller in Gefitinib (200 mg/kg) group than in
      control group (P=0.02). The average tumor volume had no significant difference
      between Gefitinib (100 mg/kg) group and control group. The average tumor volume
      of DDP or Gefitinib (100 mg/kg) plus DDP group was smaller than that of control
      group(P=0.007 and 0.001,respectively). The average tumor volume had no
      significant difference between DDP and Gefitinib (100 mg/kg) in combination with
      DDP group. The tumor inhibition rates of Gefitinib (100 mg/kg) group,Gefitinib
      (200 mg/kg) group,DDP group,and Gefitinib (100 mg/kg) plus DDP group were 26.3%,
      30.6%, 45.7% and 54.8%,respectively. The average tumor weight after treatment had
      no significant difference between Gefitinib (100 mg/kg) group and control group.
      The average tumor weights of Gefitinib (200 mg/kg) group,DDP group,Gefitinib (100
      mg/kg) plus DDP group were all smaller than that of control group. The average
      tumor weight had no significant difference between DDP group and Gefitinib (100
      mg/kg) plus DDP group. CONCLUSION: Gefitinib could inhibit the growth of NPC CNE2
      xenografts. Gefitinib in combination with DDP did not significantly potentiate
      the effect of DDP on NPC CNE2 xenografts.

PMID- 15566639
TI  - [Chimeric T cell receptor N29gamma redirect T lymphocytes response specific to
      p185HER2 in A murine model of metastatic breast cancer].
AB  - BACKGROUND & OBJECTIVE: Chimeric T-cell receptors (chTCR) are recombinant immune
      receptors with the characteristics of combining exquisite antigen specificity of
      a monoclonal antibody and activating T lymphocyte function by signal transduction
      element. Compared to "classic" TCR in mediating T cells immune response to target
      cells,a significant potential advantage of chTCR is the lack of major
      histocompatibility complex (MHC) restriction and antigen processing. N29gamma is
      a chTCR specific for p185HER2. The current study is to investigate the efficacy
      of N29gamma redirect T cells in response to p185HER2 in a murine model of
      metastatic breast cancer. METHODS: Splenic T cells from Balb/c mice were
      purificated by negative selection over sterile brushed nylon wool fiber,activated
      by immobilized purified anti-mouse CD3 and CD28 antibodies. Then the recombinant
      retrovirus pRet6N29gamma were transduced by centrifuging (1 300 g for 90 min, at
      32 Centigrade). The transduction efficiency was indirectly defermined by green
      fluorescence protein (GFP) expression of T cells in control group tested by flow
      cytometry. Mice bearing 3 days or 8 days MT901 or MT901/HER2 were randomized into
      experiment group or control group to receive IV infusions of polyclonal activated
      Balb/c splenic T cells transduced with the N29gamma retroviral vector or a
      control GFP vector(5 x 10(6)-40 x 10(6) of T cells per mouse). Each mouse was
      injected intraperitoneal with IL-2 of 3 x 10(4) IU every 12 h for 10 times. Mice
      were sacrificed at 11 days (Day 3 model) or 13 days (Day 8 model) after T cells
      transfer to enumerate the lung metastases. RESULTS: In Day 3 model, more than 200
      lung metastases were present in mice in mock group, received non-transduced T
      cells group as well as GFP transduced T cells group. Treatment of mice bearing
      HER2 positive tumor with N29gamma transduced T cells resulted in a significant
      reduction in the number of lung metastases (3.4+/-3.3/lung). In contrast,N29gamma
      transduced T cells failed to induce the regression of HER2 negative MT901
      pulmonary metastases (>200/lung). In Day 8 model, treatment with N29gamma
      modified T cells had a cell dose dependent effect on HER2+ lung metastases.
      Compared with 4 x 10(7) GFP T cells, 107 of N29gamma T cells were not enough to
      reduce the number of lung metastases (167+/-15.3) (P=0.198). With increasing
      dosage of N29gamma modified T cells from 2,3 to 4 x 10(7),there was a progressive
      decrease in the number of pulmonary metastases from 64+/-12.1,34+/-6.3,to 8+/
      4.3,respectively (P< 0.01). CONCLUSIONS: Gene engineered T cells expressing
      chimeric TCR N29gamma induced the HER2-specific regression of lung metastases in
      breast cancer. Higher doses of gene-modified T cells were necessary to eliminate
      more advanced lung metastases.

PMID- 15566640
TI  - [Observation of pathological morphology on nervous system of rat with maximum
      dose sophoridine in chronic toxic test].
AB  - BACKGROUND & OBJECTIVE: Sophoridine is a new anticancer drug with noticeable
      antitumor action and lower toxicity. No marked influence on bone marrow was found
      till now. The main toxicity is presented in nervous system. This study was to
      observe the morphological changes of the nervous system of the rats, which were
      treated with maximum dose of sorphoridine for a long time. METHODS: 30 rats,half
      of male when and half of female, were randomly divided into experimental group
      and control group. In the experimental group,rats were treated with maximum dose
      of sorphoridine [32 mg x(kg x d)(-1) ip, qd] for 60 days. In control group, rats
      were treated with the same volume of saline everyday for 60 days. The rats in
      both groups were killed at 20 d, 40 d, 60 d, and 75 d, respectively. The brain
      and spinal cord were taken out and made into pathological slices, which were
      stained by HE stain and special stain, sach as Nissel's body stain, glial
      fibrillary stain and myelin sheath stain. The differences in morphology between
      the two groups was observed. RESULTS: No pathological change was found in rats'
      cerebral cortex,internal capsul, striated body, hippocampus, substantia nigra,and
      spinal cord when the rats' were treated with sophoridine 32 mg x(kg x d)(-1) ip
      for 20 d, 40 d, 60 d. In the rats who had presented nervous system syndrome
      repeatedly or died for convulsion, or the rats who were killed in convalescence
      period (15 d after final administration), there was no pathological change
      either. CONCLUSION: No pathological changes and delayed changes in the nervous
      tissues were found when the rats were given maximum dose of Sophoridine
      continuously for 60 d. Our study showed that the syndrome of nervous system
      caused by Sophoridine is functional and stimulational, and can be recovered,and
      there is no any delayed change and sequela.

PMID- 15566641
TI  - [Enhancement of FG020326 on sensitivity of MCF-7/ADR cells to taxotere via
      enhancing activation of caspase-8 and caspase-3].
AB  - BACKGROUND & OBJECTIVE: Multidrug resistance (MDR) is often characterized by over
      expression of P-glycoprotein (P-gp) as drug efflux protein. Recent researches
      showed P-gp can inhibit caspase-dependent apoptosis, and protect MDR cells from
      apoptosis. This study was designed to investigate reversal effect of FG020326, a
      potent MDR modulator,on drug-resistance of MCF-7/ADR cells towards taxotere,and
      its mechanism. METHODS: Drug-resistant MCF-7/ADR cells, over-expressed P-gp, were
      cultured with FG020326 and taxotere. The reversal effect of FG020326 was assayed
      by MTT method. Apoptotic morphology of MCF-7/ADR cells was observed under
      fluorescent microscope after Hoechst33258 staining, cell apoptosis was measured
      by flow cytometry (FCM). Activation of caspase-8 and caspase-3 was measured by
      Western blot and colorimetric assay. RESULTS: FG020326 enhanced sensitivity of
      MCF-7/ADR cells to taxotere, and gave a 24-fold reversal of apoptosis-resistance
      with concentration of 10 micromol/L. Under effect of 10 micromol/L
      FG020326,chromatin condensation, apoptotic bodies, and sub-G1 peak were observed
      in MCF-7/ADR cells. Sensitivities of caspase-8 and caspase-3 were enhanced by
      demostrating cleavage of caspase-8, caspase-3,and PARP in MCF-7/ADR cells.
      Activities of caspase-3 and caspase-8 in MCF-7/ADR cells cultured with 10
      micromol/L FG020326 and 0.1 micromol/L taxotere were increased in a time
      dependent manner,and reached peak values at 48 h, which were significantly higher
      than those in cells cultured with taxotere alone. CONCLUSION: FG020326 may
      reverse drug-resistance of MCF-7/ADR cells towards taxotere through enhancing
      activation of caspase-8 and caspase-3 induced by taxotere.

PMID- 15566642
TI  - [Inducement of FLICE inhibitory protein antisense oligonucleotides on apoptosis
      of human gastric cancer cell line BGC823].
AB  - BACKGROUND & OBJECTIVE: Cellular FLICE inhibitory protein (cFLIP) plays an
      important role in cell apoptosis, researches of antisense oligonucleotides
      (ASODN) of cFLIP gene may provide a new method or protocol for treatment of human
      gastric cancer. This study was to explore effect of cFLIP ASODN on apoptosis of
      human gastric cancer cell line BGC823. METHODS: Human cervical cancer cell line
      HeLa was used as control, cFLIP ASODN was introduced into BGC823 cells and HeLa
      cells, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot
      were used to detect cFLIP(L/S) (cellular FLIP(Short) and cellular FLIP(long))
      mRNA and protein. The 5'FAM-conjugated ASODN was created complementary to a
      sequence that included the start site of FLIP open reading frame. After
      introducing, MTT was used to detect cell inhibition rate,TUNEL and flow cytometry
      (FCM) were used to detect cell apoptosis, and Western blot was used to detect
      protein level of cFLIP. RESULTS: The encoding mRNA and protein of cFLIP(L) and
      cFLIP(S) can be detected in both HeLa and BGC823 cells. MTT revealed that cFLIP
      ASODN significantly inhibited proliferation of BGC823 cells (P< 0.05) in a
      concentration-dependent manner. TUNEL staining detected positive FLIP expression,
      specific apoptotic peak can be detected before G1 peak by FCM, and Western blot
      revealed that protein level of cFLIP(L) and cFLIP(S) decreased significantly (P<
      0.05). CONCLUSION: The cFLIP(L/S) mRNA and encoded proteins expressed in both
      HeLa and BGC823 cells. ASODN may down-regulate cFLIP(L/S) protein level, and
      initiate apoptosis of BGC823 cells.

PMID- 15566643
TI  - [Correlation between P53 codon 72 polymorphism and tumorigenesis of cervical
      cancer].
AB  - BACKGROUND & OBJECTIVE: The p53 codon 72 polymorphism affects human
      papillomavirus (HPV) E6-mediated degradation of p53. This study was to
      investigate distribution of p53 polymorphism in Guangdong women, and relationship
      between p53 polymorphism and tumorigenesis of cervical cancer. METHODS: Cervical
      smears of 46 patients with cervical cancer (case group), and 84 patients with
      benign gynecologic tumor (control group) treated in our hospital from Sept. 2002
      to May 2003 were collected. DNA, extracted from cervical smears,were examined by
      polymerase chain reaction (PCR) for detection of HPV DNA and p53 codon 72
      polymorphism. RESULTS: Positive rate of HPV DNA in case group was 47.8%, in
      control group was 20.2%. Proportions of genotypes Arg/Arg, Pro/Pro, and Arg/Pro
      in case group were 56.5%, 21.7%,and 21.7%, respectively; in control group were
      71.4%,20.2%, and 8.3%,respectively. There were no significant differences in
      proportions of Arg/Arg (OR,0.520; 95% CI,0.245-1.102), and Arg/Pro (OR, 1.095;
      95% CI,0.454-2.639) between 2 groups; proportion of Pro/Pro in case group was
      significantly higher than control group (OR, 3.056; 95% CI,1.076-8.678), but no
      significant difference was found in women with HPV infection. CONCLUSION: Arg/Arg
      genotype is not a high-risk factor for cervical cancer in Chinese population, and
      individuals with Pro/Pro genotype are likely to develop cervical cancer.

PMID- 15566644
TI  - [Meta analysis of relationship between laryngeal tumor of chinese and human
      papillomavirus infection].
AB  - BACKGROUND & OBJECTIVE: Researches showed that the infection of human
      papillomavirus (HPV) was closely related to laryngeal tumor, but those results
      existed great differences because of different research methods. In this study
      Fisher's and Meta analysis were used to synthetically evaluate relationship
      between laryngeal benign and malignant tumors of Chinese and infection of
      different types of HPV. METHODS: A total of 123 references about relationship
      between laryngeal benign and malignant tumors of Chinese and infection of
      different types of HPV were collected from CBMdisc (Chinese Biomedical Literature
      Analysis and Retrieval System for Compact Disc). There were 11 references
      accorded with research criteria which were case-control study, and had detected
      HPV16 or HPV6/11 by polymerase chain reaction (PCR). Fisher and Meta analysis
      were used to quantitatively and qualitatively analyze these references
      synthetically. RESULTS: Mean detection rates of HPV16 in normal laryngeal tissue,
      laryngeal carcinoma (LC), laryngeal papilloma(LPa), laryngeal polyp (LPo) from
      all references were 10.8%,35.2%,27.5%,5.0%, respectively; and those of HPV6/11
      were 8.7%, 18.6%, 61.6%, 21.9%, respectively. The infection of HPV16 in LC were
      significantly higher than those in LPa, and LPo (P< 0.005); the combined odds
      ratio (ORc) for HPV16 infection in LC was 2.8 (1.7-4.7) times that in LPa, and
      12.7 (4.2-38.8) times that in LPo; mean positive rate of HPV16 in LC was 22.0%
      (12.2%-31.8%) higher than that in LPa, and 39.0% (19.4%-58.6%) higher than that
      in Lpo. The infection of HPV6/11 in LPa was significantly higher than that in LC
      (P< 0.005); OR(c) for HPV16 infection in LPa was 16.4 (5.6-48.1) times that LC;
      mean positive rate of HPV16 in LPa was 56.0% (34.4%-75.6%) higher than that in
      LC. There was no significant difference of HPV6/11 infection between LC and LPo
      (P >0.05). CONCLUSION: The infection of HPV16 may enhance risk of development of
      laryngeal carcinoma; and the infection of HPV6/11 may enhance risk of development
      of laryngeal papilloma.

PMID- 15566645
TI  - [Comparison of pelvic transarterial chemoembolization with lipiodol ultra-fluid
      carboplatin and transarterial carboplatin through experiment in dogs].
AB  - BACKGROUND & OBJECTIVE: Transarterial chemoembolization, based on transarterial
      chemotherapy, is a new treatment for malignant neoplasms. This study was to
      investigate distribution of platinum (Pt) in blood and uterine tissue after
      infusing different carboplatin arterially. METHODS: Fourteen female dogs were
      randomly divided into 2 groups: embolizational group (group A, 7 dogs),and
      chemotherapy group (group B, 7 dogs). In group A, carboplatin (12 mg/kg), mingled
      with lipidol ultra-fluid (0.2 ml/kg), was injected into dogs' iliac arteries. In
      group B, carboplatin (12 mg/kg), dissolved in 5% glucose, was injected into the
      same arteries. The uterine tissues and blood samples were collected at different
      time points, concentrations of Pt in samples were measured by atomic absorption
      method. RESULTS: Peak concentration of Pt in uterine tissues of group A was
      (215.0+/-17.6) microg/g, that of group B was (211.3+/-40.1) microg/g (P >0.05),
      the peak appeared at 0 min in both groups. Area under concentration-time curve
      (AUC) of Pt in tissues of group A was (13.9+/-3.9) mg x min x g(-1),
      significantly larger than that of group B (5.9+/-0.6) mg x min x g(-1). Peak
      concentration of Pt in plasma of group A was (8.7+/-12.5) microg/g, that of group
      B was (16.7+/-3.6) microg/g. AUC(0-240 min) was (0.5+/-0.1) mg x min x g(-1) in
      group A,and (1.2+/-0.4) mg x min x g(-1) in group B (P< 0.05). CONCLUSION:
      Compared with arterial chemotherapy, arterial chemo- embolization may result in
      higher Pt concentration in local area, and lower Pt concentration in plasma, it
      may reduce the systemic toxicities, and enhance local effect on tumor.

PMID- 15566646
TI  - [CHL prevent colon neoplasms in mice and its selective inhibition on COX-2].
AB  - BACKGROUND & OBJECTIVE: Chlorophyllin (CHL) was proved to have strong anti
      inducement effect toward many mutagens and epicarcinogens. This study was to
      explore effect of CHL in preventing colon neoplasms in mice induced by
      dimethylhydrazine (DMH), and the selective inhibition on cyclooxygenase 2(COX-2).
      METHODS: The colorectal neoplasms were induced with DMH in mice and the different
      dose of CHL were administered in different phases, then the prevention of
      colorectal neoplasms by CHL was examined; The IC50 and growth curve of HT29 cells
      were measured with MTT method after treated with CHL; The effect of CHL on the
      expression of COX-1 mRNA and COX-2 mRNA in HT29 cells were measured with RT-PCR
      method; The effect of CHL on the expression of COX-2 protein and NF-kappaB
      protein were measured with western blot and immunohistochemistry methods.
      RESULTS: The incidence of colon cancer, average tumor amount, and percentage of
      carcinoma in CHL group were significantly lower than those in DMH group (P< .05);
      CHL could inhibit the growth of HT29 cells. The effects were dose dependent; CHL
      could selectively inhibit the expression of COX-2mRNA in HT29 cells,the
      expression of COX-2 protein in colon neoplasms and HT29 cells, and the expression
      of NF-kappaB protein in colon neoplasms. CONCLUSIONS: CHL could prevent colon
      neoplasms in mice induced by DMH and the preventive effect related to selective
      inhibition on COX-2, furthermore, the inhibition of CHL on COX-2 was realized by
      inhibiting NF-kappaB protein.

PMID- 15566647
TI  - [Expression and significance of survivin in colon cancer].
AB  - BACKGROUND & OBJECTIVE: Survivin is a newly identified apoptosis inhibitor.
      Studies indicated that Survivin over-expressed in malignant tumors. This study
      was designed to evaluate the expression of Survivin in colon cancer,and the
      correlation of its expression to clinical characteristics and prognosis of
      patients with colon cancer. METHODS: Expression of Survivin protein was
      investigated by immunohistochemistry in 12 cases of normal colon tissues,and 79
      cases of colon cancer tissues without the history of radiotherapy or
      chemotherapy. RESULTS: Expression of Survivin was detected in 78.5%(62/79) of
      colon cancer tissues,higher than that in tumor nests adjacent tissues, which was
      32.9% (26/79). In contrast, normal colon tissues did not express Survivin. There
      was no relationship between the expression of Survivin and age, sex, blood type,
      serum CEA level, lymph node metastasis, histological grade, infiltration degree,
      and Dukes' stage(P >0.05). When 25% was used as the cut-off point between high
      and low expression of Survivin, 3-year overall survival rate of low expression
      group (63.56%) was much higher than that of high expression group (39.96%)
      (P=0.04). Cox proportional hazards model analysis showed that Dukes' stage, and
      high expression of Survivin were the only 2 prognosis factors influenced the
      survival times (Wald values were 24.225, and 5.504, respectively, P values were
      0.000, and 0.019, respectively). CONCLUSIONS: There is a high expression level of
      Survivin in colon cancer, it may play an important role in tumorgenesis and
      development of colon cancer. Over-expression of Survivin was related with poor
      prognosis, it may be a potential prognostic index.

PMID- 15566648
TI  - [Expression of adhesive molecule CD44v6 and p53 gene in breast cancer tissues and
      its relation with DNA ploidy].
AB  - BACKGROUND & OBJECTIVE: The variant form,CD44v6, of cellular surface adhesive
      molecule CD44 plays an important role in tumor metastasis, but the research
      results of its expression in breast cancer have obvious differences. Mutant of
      p53 gene was the most common gene abnormality associated with tumorigenesis of
      human. This study was to explore expression, and mutual relationship of p53,
      CD44v6, and DNA ploidy in breast cancer. METHODS: Flow cytometry was used to
      analyze expression level of p53, CD44v6, and DNA ploidy in 52 specimens of breast
      cancer tissues and adjacent noncancerous tissues, and 18 specimens of benign
      breast tumor tissues. RESULTS: Expression levels of p53 and CD44v6, S phase
      fraction (SPF), and proliferation index (PI) in breast cancer tissues were higher
      than those in adjacent noncancerous tissues, benign breast tumor tissues, and
      normal breast tissues (P< 0.05). Expression of p53, CD44v6, SPF, and PI had no
      relation with patients' age, pathologic type, tumor size, and clinical stage (P
      >0.05). Expression of p53,CD44v6, SPF, and PI in patients with lymph node
      metastasis were higher than those in patients without lymph node metastasis (P<
      0.05). Of 52 breast cancer patients, 23 were aneuploid (44.23%), 20 of 23 had
      metastasis; 29 were diploid (55.77%), 17 of 29 had metastasis. Lymph node
      metastasis rate in aneuploid patients was higher than that in diploid patients
      (P< 0.05); expression level of p53 protein in aneuploid tumors was higher than
      that in diploid tumors (P< 0.05), but this phenomenon was not seen in CD44v6
      expression (P >0.05). The correlation analysis revealed that p53 protein
      expression positively correlated with SPF and PI (P< 0.05), whereas CD44v6
      expression didn't correlate with SPF and PI (P >0.05). CONCLUSION: Expression of
      p53 and CD44v6,and DNA content may play important roles in tumorigenesis, and
      progression of breast cancer. Expression of p53 and CD44v6,DNA ploidy, SPF, and
      PI may be correlated with lymph node metastasis. p53 and CD44v6 gene, and DNA
      content may become prognostic factors of breast cancer.

PMID- 15566649
TI  - [Expression of angiogenic factors and their clinical significances in acute
      myeloid leukemia].
AB  - BACKGROUND & OBJECTIVE: To investigate the expression of vascular endothelial
      growth factor (VEGF) & basic fibroblast growth factor (bFGF) in primary acute
      myeloid leukemia (AML) cells, and study plasma VEGF& bFGF concentration in
      patients with AML and the two factors' clinical significance. METHODS: VEGF&bFGF
      and their receptors mRNA expression were detected by RT-PCR; VEGF & bFGF plasma
      level was analyzed by ELISA. RESULTS: In 107 AML patients, the positive mRNA
      expression rate of VEGF, KDR and Flt1 was 56.1%, 49.5%, and 2.8%, respectively;
      for bFGF and FGFR1-4, the positive rate was 21.5%, 35.5%, 9.4%, 35.5% and 23.4%,
      respectively. VEGF concentration in AML (154.75+/-109.98) pg/ml was significantly
      higher than that in AML-CR (72.05+/-23.39) pg/ml and the normal control (99.91+/
      41.87) pg/ml (P< 0.05). Nevertheless, the level of bFGF had no significant
      difference among AML, AML-CR and the normal control. VEGF level (124.05+/-76.57)
      pg/ml in patients, who got complete remission (CR) after 2 cycles of
      chemotherapy, was remarkably lower than that (211.243+/-169.88) pg/ml in patients
      without CR (P< 0.05). Furthermore, the higher the concentration of VEGF & bFGF,
      the shorter the survival was. CONCLUSION: VEGF& bFGF and their receptors mRNA in
      leukemic patients could be expressed to some degree,and our investigation
      suggested VEGF &bFGF and their receptors probably be produced by autocrine or
      paracrin. Abnormally high level of VEGF may be a poor factor for chemotherapy and
      survival in AML. The prognosis of patients with AML may be improved by treating
      VEGF and their receptors as therapy targets.

PMID- 15566650
TI  - [Primary assessment of treatment effect of thymosin alpha1 on chemotherapy
      induced neurotoxicity].
AB  - BACKGROUND & OBJECTIVE: Clinical trails showed that thymosin alpha1 offers
      protection from toxicities (nausea, vomiting, fatigue) of chemotherapy. This
      study was designed to investigate the protection of thymosin alpha1 to nervous
      system. METHODS: Twenty-two patients with advanced lung cancer, or advanced
      breast cancer were treated with vinorelbine (25 mg/m(2), d(1), d(8)) combined
      with cisplatin (80 mg/m(2), d(1)), or gemcitabine (1.25 g/m(2), d(1), d(8))
      combined with cisplatin (80 mg/m(2), d(1)),or paclitaxel (80 mg/m(2), d(1), d(8),
      d(15)) combined with carboplatin (AUC=6 d(1)),or paclitaxel (80 mg/m(2), d(1),
      d(8), d(15)) combined with epirubicin (80 mg/m(2), d(1)). They all experienced
      grade 2 to 4 of neurotoxicities according to common toxicity criteria of National
      Cancer Institute after chemotherapy. The same chemotherapy regimens were combined
      with thymosin alpha1 (1.6 mg/d for 4 days before chemotherapy, and 1.6 mg twice
      weekly for 1-3 weeks after chemotherapy began) in the next cycle. Clinical
      neurologic evaluation was performed at baseline every week. RESULTS: In 10
      patients (45.4%), neurotoxicities reduced from grade 2-4 before chemotherapy to
      less than grade 2 after chemotherapy. CONCLUSION: Thymosin alpha1 may prevent
      patients from chemotherapy-induced neurotoxicities.

PMID- 15566651
TI  - [A tolerability study of A cremophor-free albumin bound nanoparticle paclitaxel
      intravenously administered in patients with advanced solid tumor].
AB  - BACKGROUND & OBJECTIVE: Capxol is a Cremophor-free,protein stabilized,
      nanoparticle formulation of paclitaxel. This phase I study was designed to
      evaluate the tolerability/safety, toxicity profile, and maximum tolerated dose
      (MTD) of Capxol administered intravenously in Chinese patients with advanced
      solid tumor, and to provide the recommending dose for the phase II trial. METHOD:
      Capxol was administered intravenously over 30 minutes, no premedication was
      required. Doses of Capxol ranged from 135 to 350 mg/m(2). The treatment was
      repeated at 3 weeks interval. RESULTS: 22 patients were treated with Capxol and
      totally 94 treatments cycles were completed. No acute hypersensitivity reactions
      were observed during the infusion period. The treatment was tolerated well. Most
      of AEs (95%) were grade 1/2; >/= grade 3 AEs were only 5%. The most common
      toxicities were mild leucopenia and peripheral sensory neuropathy. The dose
      limiting toxicities,which occurred at dose level of 350 mg/m(2),were grade 4
      neutropenia (1 out of 3 patients) and grade 3 diplopia (1 out of 3 patients). The
      MTD was thus determined at 300 mg/m(2). Among 21 patients who were evaluable for
      efficacy, 1 CR, 7 PR, 9 SD, 4 PD were observed, overall response rate (CR+PR) was
      38%. CONCLUSION: This phase I trial has demonstrated that Capxol has several
      advantages on clinical application, which include non-premedication required,
      shorter infusion time,higher paclitaxel MTD and safer toxicity. The results
      support for that a phase II clinical trial to further evaluate the antitumor
      activity of this drug in Chinese patients is worthy. The recommended dose for
      phase II clinical trial is 260 mg/m(2), I.V. over 30 minutes,and treatment
      repeats at every 3 weeks.

PMID- 15566652
TI  - [Distribution of CD8+CD28- T cells and CD3+CD56+ NKT cells in peripheral blood of
      patients with B-cell non-Hodgkin's lymphoma].
AB  - BACKGROUND & OBJECTIVE: Patients with B-cell non-Hodgkin's lymphoma (B-NHL)
      usually have a poor immune response. CD8(+)CD28(-) T cells (Ts) and CD3(+)CD56(+)
      NKT cells (NKT) are new types of immune suppressor cells. This study was to
      analyze proportions and changes of them in peripheral blood of patients with B
      NHL, explore their effects on immunosuppression of B-NHL, and the influnce
      factors, to provide reference for intervening in immune function of B-NHL
      patients. METHODS: Peripheral blood samples were got from 79 naive patients with
      B-NHL before treatment, and 25 healthy people, samples of 18 patients who got
      complete remission (CR) after 4-6 cycles of chemotherapy were collected either
      before chemotherapy or after CR. Proportions of Ts and NKT were analyzed by flow
      cytometry (FCM). RESULTS: Compared with control group, proportions of Ts, and NKT
      in peripheral blood of B-NHL patients before chemotherapy were (18.19+/-5.03)%,
      and (6.08+/-3.29)%, significantly higher than those of healthy people [(11.20+/
      3.49)%, P< 0.01; (3.52+/-1.56)%, P< 0.01]. There were no significant differences
      of proportions of Ts among patients with B-NHL of different clinical stages (P
      >0.05), and different malignant grade (P >0.05), and between before treatment and
      after CR (P=0.55). No significant difference of proportions of NKT was found
      among patients with B-NHL of different clinical stages (P >0.05), and different
      malignant grade (P >0.05), and between before treatment and after CR (P=0.39).
      CONCLUSION: Populations of Ts and NKT commonly increased in peripheral blood of
      patients with B-NHL, they may play roles in immunosuppression of B-NHL.

PMID- 15566653
TI  - [Clinical outcomes of 106 patients with peripheral T-cell lymphoma treated by
      standard CHOP regimen].
AB  - BACKGROUND & OBJECTIVE: T-cell Non-Hodgkin's lymphoma (NHL) are common in Asia,
      It's biological behavior is different from B-cell NHL. It often shows lower chemo
      sensitivity, high incidence of relapse and poor prognosis. This study was
      designed to analyse the clinical characteristics and to evaluate the
      effectiveness and toxicity of standard CHOP regimen in the treatment of
      peripheral T-cell lymphomas-unspecified (PTCL-U) according to the Revised
      European- American Lymphoma (REAL) classification. METHODS: 106 patients with
      PTCL-U were treated by standard CHOP regimen with or without involved field
      radiotherapy from January 1997 to December 2003 in Cancer Center, Sun Yat-sen
      University, The clinical characteristics, response and long-term survival rates
      were analysed, retrospectively. RESULTS: Early stages (I-II) were present in
      78.3% (83/106) of the patients. Extranodal involvement account for 84.0% (89/106)
      with 34.9% (37/106) of more than 1 involved extranodal sites. The percentage of
      IPI score 0-1 was 78.3% (83/106). All the patients were treated by standard CHOP
      regimen plus IFRT for bulky disease. 55.7% (59/106) patients were treated by
      chemotherapy alone and 43.3% (46/106) were treated by chemotherapy plus
      radiotherapy. The overall response rate was 81.0% (85/105) with 58.2%(65/105)
      complete remission (CR) rates. The response rate of chemotherapy alone were 69.5%
      (41/59) and CR rates was 44.1% (26/59). The median duration of response was 16
      months (1-88 months). The actual 1, 3 and 5 year overall survival rates were
      69.9%, 42.9% and 22.0%, respectively. Median survival times were 24 (12-36)
      months. CONCLUSION: Long-term survival of PTCL-U treated by standard CHOP regimen
      were poor. Further investigation is wanted.

PMID- 15566654
TI  - [Primary study of relationship between serum level of VEGF and non-Hodgkin's
      lymphoma in children and adolescent patients].
AB  - BACKGROUND & OBJECTIVE: Angiogenesis is an important mechanism in morbility of
      malignant tumor, vascular endothelial growth factor (VEGF) is the key factor.
      This study was to investigate the serum level of VEGF in children and adolescent
      patients with non-Hodgkin's lymphoma (NHL). METHODS: The serum levels of
      VEGF(sVEGF) in 24 pretreated NHL patients were detected by ELISA. sVEGF in 10 of
      the 24 patients who received complete response after treatment were also detected
      by ELISA. RESULTS: The average serum VEGF level was 745.79 ng/L (40.64-3623.09
      ng/L)in 24 NHL patients. It was higher than normal [(294.20+/-23.40) ng/L]. sVEGF
      in 18 of the patients were higher than the standard, while in 6 of the patients
      were lower than the standard. The average serum VEGF level was 289.54 ng/L (35.11
      826.8 ng/L) in 10 of The CR patients, 8 cases of them had a high VEGF level
      before treatment but a nearly normal level after first CR. And 2 cases of them
      had normal level during the course. CONCLUSIONS: The serum level of VEGF in NHL
      patients was higher than normals. The high serum level of VEGF has a tendency to
      drop to the normal standard after receiving CR. From the clinical data, a high
      serum level was not found associated with stage, gender, PS. score, IPI score,
      serum LDH and "B" symptoms et al.

PMID- 15566655
TI  - [Clinical analysis of liver non-Hodgkin's lymphoma].
AB  - BACKGROUND & OBJECTIVE: Incidence of liver non-Hodgkin's lymphoma (NHL) is
      increasing. This study was to explore clinical features, diagnosis, treatment,
      and prognosis of liver NHL. METHODS: Records of 45 patients with liver NHL
      treated in our hospital from Jan. 1998 to May 2002, 9.6% of all NHL patients
      treated in the same period, were retrospectively analyzed with statistic software
      package of SPSS10.0. RESULTS: Of 45 patients, 32 were male,and 13 were female,
      the median age was 50 years. Immunophenotyping revealed that 24 cases were T cell
      original, 19 were B cell original, and 2 were undefined. According to
      International Work Formulation (IWF), 92% of 45 patients belonged to intermediate
      grade. Clinical features of liver NHL were presented with fever, jaundice,
      hepatosplenomegalia, and liver dysfunction. Combination treatment based on
      chemotherapy was the major therapy. Median survival time was 4 months, overall 1
      , and 2-year survival rates were 22%, and 18%. CONCLUSION: Early diagnose liver
      NHL is difficult, its treatment effect and prognosis are poor, combination
      therapy should be given as early as possible.

PMID- 15566656
TI  - [Gemcitabine plus cisplatin versus gemcitabine plus vinorelbine in treatment of
      advanced non-small cell lung cancer (NSCLC)].
AB  - BACKGROUND & OBJECTIVE: Although platin-based chemotherapy has become a standard
      treatment for non-small cell lung cancer (NSCLC), its severe toxicities limit
      clinical application, and a new replacement is required. The study was to
      evaluate the efficacy, survival rate and toxicity between the combination of
      gemcitabine and cisplatin (GP arm) and the combination of gemcitabine and
      vinorelbine (GN arm) in the treatment of advanced NSCLC. METHODS: Eighty-two
      patients with locally advanced or metastatic NSCLC were enrolled into this study.
      42 patients and 40 patients were randomized into GP group and GN group
      respectively. The patients' characteristics were similar between the two groups.
      They were treated with gemcitabine (1 000 mg/m(2) d(1), d(8)) plus cisplatin (80
      mg/m(2), d(1)) in GP group, or gemcitabine plus vinorelbine (25 mg/m(2) d(1),
      d(8)) in GN group. The chemotherapy was repeated every 3 weeks as a cycle. Every
      patient was treated two cycles at least. RESULTS: An objective response rate of
      28.6% was observed in GP arm versus 25% in GN arm (P=0.346). The 1-year survival
      rate was 64% in GP arm and 66% in GN arm. The median survival time was 9.87
      months for GN arm and 8.78 months for GP arm. Nausea and vomiting were the major
      dose-limiting toxicity. The incidence of grade III/IV nausea and vomiting was
      significantly higher in the GP arm than in the GN arm (P=0.000). The Leukopenia
      incidence was similar in two groups (P=0.130). CONCLUSION: The efficacy of GN
      regimen (platinum-free regimen) was similar to that of GP regimen, but the
      toxicity of GN regimen is lighter than that of GP regimen.

PMID- 15566657
TI  - [Paclitaxel and cisplatin combined with etoposide chemotherapy in non-small cell
      lung cancer with brain metastases].
AB  - BACKGROUND & OBJECTIVE: Chemotherapy has been rarely considered an important
      treatment modality for non-small cell lung cancer (NSCLC) with brain metastases
      (BM) because of the existence of blood-brain barrier (BBB). In the recent
      years,the studies about BBB suggest that many agents (such as paclitaxel,
      cisplatin) have increased permeability to BBB once BM occur. Therefore, we
      addressed the role of this combination with paclitaxel,etoposide, cisplatin (some
      effective agents to NSCLC) as front-line therapy in NSCLC with BM. METHODS: 20
      chemotherapy-naive patients with documented BM from NSCLC and at least one
      evaluable extracerebral lesion were treated with paclitaxel (150 mg/m(2)) on day
      1, etoposide (60 mg/m(2)) on day 1,3,5,and cisplatin (20 mg/m(2)) on day 1-5. The
      cycle was repeated every 28 days. RESULT: 17 patients were evaluated for response
      and 19 for toxicity. The intracranial objective response rate (ORR) was 41%,the
      extracranial ORR was 53%. Patients who responded for the brain also had a
      response at the extracerebral sites. Grade 3-4 myelosuppression occurred in 21%
      of the patients. The overall medican follow-up was 9 months. The medican survival
      time for the 9 died patients was 8.5 months. CONCLUSIONS: Paclitaxel and
      cisplatin combined with etoposide as front-line therapy in NSCLC with BM has some
      efficacy. The toxicity is mild. This combination chemotherapy seems to achieve
      responses similar to those for extracranial diseases, and further support the
      need for reconsideration of the role of chemotherapy in this setting.

PMID- 15566658
TI  - [Postoperative adjuvant therapy for 189 patients with completely resected non
      small cell lung cancer of stage III(A)].
AB  - BACKGROUND & OBJECTIVE: Postoperative adjuvant therapy for patients with
      completely resected non-small cell lung cancer (NSCLC) of stage III(A) is a hot
      research topic. This study was to discuss the influence of postoperative adjuvant
      radiotherapy and chemotherapy on survival time of patients with completely
      resected NSCLC of stage III(A). METHODS: Clinical data of 189 patients with
      completely resected NSCLC of stage III(A) treated in our hospital from Jan. 1995
      to Jan. 2000 were retrospectively analyzed to evaluate the influence of
      postoperative radiotherapy and chemotherapy on patients' survival time. RESULTS:
      Median survival time of 68 patients with squamous cell carcinoma was
      significantly higher than that of 121 patients with adenocarcinoma (43.8 months
      vs. 26.8 months, P=0.038). Of 68 patients with squamous cell carcinoma, median
      survival time of 21 patients treated by surgeon alone had no significant
      difference with that of 28 patients received postoperative radiotherapy (42.8
      months vs. 45.5 months, P=0.068), and 19 patients received postoperative
      chemotherapy (42.8 months vs. 52.0 months, P=0.075). Of 121 patients with
      adenocarcinoma, median survival time of 41 patients treated by surgeon alone has
      no significant difference with that of 43 patients received postoperative
      radiotherapy (26.7 months vs. 26.6 months, P=0.555), and 37 patients received
      postoperative chemotherapy (26.7 months vs.37.9 months, P=0.242). CONCLUSIONS:
      Pathologic type is the main factor that may affect survival time of patients with
      resectable NSCLC of stage III(A). Although no statistical significance appeared,
      postoperative adjuvant chemotherapy tend to prolong patients' survival time.

PMID- 15566659
TI  - [Pamidronate in treatment of pain caused by bone metastasis].
AB  - BACKGROUND & OBJECTIVE: Clinical studies showed that pamidronate has curative
      effects on pain induced by bone metastasis. This study was to observe curative
      effects, and side effects of different dosages of pamidronate on pain induced by
      bone metastasis. METHODS: Ninety patients with metastatic bone tumor were divided
      into 2 groups randomly. In group A, 120 mg pamidronate was given by intravenous
      infusion in 3 days (60 mg day(1), 30 mg day(2-3)); in group B, 90 mg pamidronate
      was given by intravenous infusion in 3 days (30 mg day(1-3)), repeated every 4
      weeks. RESULTS: The notable effect, effect, and no effect were observed in 20,
      23, and 2 patients of group A, and 16, 20, and 9 patients of group B,
      respectively. Total effective rate in group A was 95.6%(43/45) , in group B was
      80.0% (36/45) (P< 0.05). Curative rate within 1 course of treatment in group A
      was 88.9% (40/45), in group B was 57.8% (26/45) (P< 0.01). Curative rate within 1
      week in group A was 80% (36/45) , in group B was 57.8% (26/45) (P< 0.05). Side
      effects were observed in 3 patients (6.7%). CONCLUSIONS: Pamidronate has good
      curative effects in treating pain induced by bone metastasis. Efficacy of 120 mg
      pamidronate is better than 90 mg pamidronate.

PMID- 15566660
TI  - [Observation of clinical response of "sheng ban recipe" for platelets decrease
      after chemotherapy].
AB  - BACKGROUND & OBJECTIVE: The majority of cancer chemotherapy can lead to bone
      marrow depression, which often affects clinical response as chemotherapy can not
      be carried out with enough dosage on time. The platelets decrease is one of the
      problems caused by bone marrow depression. Though the clinical response of
      hyodermic "IL-11" is affirmed to advance platelets presently, it is limited by
      expensive price. Other agents that can be taken orally with suitable price and
      equal authenticity are less reported. The author observed clinical response of
      platelets decrease adopting traditional Chinese medicine "Sheng Ban Recipe"(SBR).
      METHODS: Totally 103 patients with platelets decrease after chemotherapy from
      July 1994 to Jannary 2002. They were randomly divided into two groups: SBR plus
      common treatment group and common treatment alone group. The previous group take
      1 package SBR for twice drink per day. Common treatment group give common therapy
      only. The follow-up period is 2 weeks. RESULTS: Among the 55 cases in SBR group,
      noticeable efficiency 20%, efficiency 50.9%, total efficiency 70.9%, which is
      evidently superior to common group. CONCLUSION: "Sheng Ban Recipe" can
      effectively treat thrombocytopenia after chemotherapy, which helps to reduce the
      necessary of intravenous drip of platelets and the risk of hemorrhage.

PMID- 15566661
TI  - [Chemoradiotherapy followed by surgery in treatment of locally advanced
      esophageal carcinoma: a phase II trial].
AB  - BACKGROUND & OBJECTIVE: Recently, neoadjuvant therapy has become the focus of
      interest in an effort to prolong survival and reduce recurrence rates in patients
      with oesophageal cancer. This study was designed to evaluate the tolerance and
      the short-term outcome of chemoradiotherapy followed by surgery for patients with
      locally advanced esophageal squamous carcinoma, to observe effects of
      chemoradiotherapy on tumor resection rate, incidence of complications after
      surgery, and perioperative mortality. METHODS: From January 2000 to September
      2003, Thirty-four consecutive patients with locally advanced esophageal squamous
      carcinoma were entered into this phase II study. The clinical pre-treatment
      staging of the tumors were determined by chest CT scan, abdomial CT Scan, EUS,
      and bronchoscopy examination. Chemotherapy and radiotherapy were performed
      concurrently. The chemotherapy consisted of Vinorelbine (or 5-Fluorouracil) and
      Cisplatin. 5-Fluorouracil at 2.4 g/m(2) was administered in continuous infusion
      for days 1-3 and days 22-25. Vinorelbine at 25 mg/m(2) per day was administered
      in bolus infusion on d1, d8, d22 and d29. Cisplatin at 75 mg/m(2) was
      administered by intravenously infusion on d1 and d22. A total radiotherapy dose
      of 40 Gy was delivered in 20 daily fractions of 2.0 Gy each (given 5 d/wk for 4
      weeks). After completion of chemoradiotherapy, clinical restaging was performed.
      Esophagectomy and lymphadenectomies were performed 3-5 weeks after
      chemoradiotherapy. RESULTS: Thirty-three patients completed the planned
      chemoradiotherapy, and 32 patients underwent surgery. The toxicities of
      chemoradiotherapy such as myelotoxicity, pulmonary toxicity, esophagitis were
      grade I or II. No death was resulted from chemoradiotherapy. The clinical
      response rate of chemoradiotherapy was 85.3%, the pathological complete response
      rate was 25%, the resectability rate was 100%. Postoperative pulmonary infection
      occurred in 8 patients (22.9%), anastomotic leak in 3 patients (9.4%). Two
      patients (6.3%) died perioperatively because of ARDS and anastomotic leak
      complicated with heart failure. CONCLUSIONS: The short-term results of this study
      suggest that the strategy of chemoradiotherapy followed by surgery is
      safe,although it caused considerable toxicity and increased operation-related
      complications rate and perioperative mortality rate compared with surgery alone
      at the same period. Preoperative chemoradiotherapy is able to significantly
      reduce the tumor stage, and achieve substantially high clinical response rate and
      pathological complete response rate.

PMID- 15566662
TI  - [Comparison of shaft temperature related treatment efficacy between "air-cooled"
      microwave coagulation and traditional microwave coagulation].
AB  - BACKGROUND & OBJECTIVE: The application and development of traditional
      percutaneous microwave coagulation therapy (PMCT) has been limited by high shaft
      temperature. The "air-cooled" PMCT is the newest advancement. This study was to
      compare shaft temperature related treatment efficacy between "air-cooled" PMCT
      and traditional PMCT. METHODS: Two pigs underwent traditional PMCT, and "air
      cooled" PMCT at 80 W for 10 min separately. Skin injury, surface temperature of
      guide-needle, charring tissue sticking to the shaft, and lesion shape in 2 pigs
      were compared. Five patients with liver tumor received traditional PMCT, and 8
      patients with liver tumor received "air-cooled" PMCT. Feeling of pain, skin
      injury, charring tissue sticking to the shaft, local therapeutic efficacy, and
      recurrence of these 2 groups of patients were compared. RESULTS: In the pig
      underwent traditional PMCT, surface temperature of guide-needle reached 119-160
      Centigrade; skin burn around puncture points was serious; charring tissue stuck
      to the front of electrodes; a trail sign was observed in coagulated lesion. In
      the pig underwent "air-cooled" PMCT, surface temperature of guide-needle was 28.8
      39.9 Centigrade; no skin injury was found around puncture points; no charring
      tissue stuck to the front of electrodes; no obvious trail sign was observed in
      coagulated lesion. In 5 patients received traditional PMCT, 3 had skin injury; 2
      had charring tissue stuck to the front of electrode; all felt moderate or serious
      epigastric pain lasted for 1-8 weeks; 4 had complete coagulation; 1 had local
      recurrence. In 8 patients received "air-cooled" PMCT, no one had skin injury, and
      charring tissue stuck to "air-cooled" electrode; 4 felt slight epigastric pain
      within 1 week; all had complete coagulation; no local recurrence was found.
      CONCLUSIONS: The technique of "air-cooled" electrode may decrease temperature of
      shaft safely and reliably, and eliminate side effects arose from high temperature
      of shaft. Treatment efficacy of "air-cooled" PMCT is better than that of
      traditional PMCT.

PMID- 15566663
TI  - [Significance of membrane type-1 matrix metalloproteinase expression in breast
      cancer].
AB  - BACKGROUND & OBJECTIVE: Recent researches manifested that MT1- MMP (Membrane type
      1 matrix metalloproteinase) is essential for breast cancer invasion and
      metastasis, but there are few reports about the clinical value of MT1- MMP. This
      study was designed to investigate the clinical significance of MT1-MMP protein
      and mRNA expression in human breast cancers. METHODS: Forty-six human breast
      cancer tissues were collected. MT1-MMP protein and mRNA expression were detected
      by semi-quantitative reverse transcriptase chain reaction (RT-PCR) and
      immunohistochemistry assay and their correlations with clinicopathological
      factors were analyzed. RESULTS: The expression of MT1-MMP protein was positive in
      52.2% of forty-six breast cancer tissues. The positive rates were 12.5%, 54.8%
      and 85.7% in stageI, stage II and stage III human breast cancers, respectively (P
      < 0.05), and 11.1%, 59.4% and 80.0% in the group of T(1), T(2) and T(3) (P <
      0.05), and 27.3%, 66.7% and 100.0% in the group of N(0), N(1) and N(2) (P <
      0.05). MT1-MMP mRNA expression were detected in all of the carcinomas. The means
      of MT1-MMP mRNA expression relative quantities were 0.4730, 0.6950 and 0.9100 in
      stageI, stage II and stage III human breast cancers, respectively (P < 0.05), and
      0.5240, 0.7150 and 0.8220 in the group of T(1),T(2) and T(3) (P < 0.05), and
      0.6305, 0.7022 and 0.8700 in the group of N(0), N(1) and N(2)(P < 0.05). There
      were no relations between the MT1-MMP protein or mRNA expression and ER, PR or C
      erbB-2(P >0.05). CONCLUSION: MT1-MMP protein and mRNA expression in human breast
      cancers had positive correlation with the stage,the tumor size and lymph node
      metastasis. MT1-MMP can be a predictor for the ability of breast cancer invasion
      and metastasis.

PMID- 15566664
TI  - [Phonation reconstruction and function assessment after total and near-total
      laryngectomy].
AB  - BACKGROUND & OBJECTIVE: Total laryngectomy is a common surgery pattern for
      treating laryngeal and hypopharyngeal cancer, but patients will lost phonation
      function after operation. This study was to retrospectively analyze usage of
      modified Amatsu, and modified Pearson operation in treating laryngeal and
      hypopharyngeal cancers, and to analyze phonation function by subjective and
      objective assessment. METHODS: Clinical data of 69 patients with laryngeal or
      hypopharyngeal cancer treated by total or near-total laryngectomy (modified
      Amatsu or modified Pearson operation) in our department from 1996 to 2003 were
      retrospectively analyzed. Phonation function of 69 patients was evaluated by
      acoustic analysis and Jiyan classification method, and compared with phonation
      quality of patients received vertical hemilaryngectomy (VHL) and healthy people.
      RESULTS: No patient appeared obvious aspiration. Four cases with post-operative
      radiotherapy all regained phonation function. The 3-year survival rate was 88%
      (22/25); 5-year survival rate was 80% (4/5). Results of acoustic assessment, and
      Jiyan classification method indicated that phonation function of patients
      received modified Amatsu or modified Pearson operation could meet daily
      requirements. CONCLUSIONS: Modified Amatsu and modified Pearson operations can be
      learnt and applied easily for phonation reconstruction after laryngectomy. They
      may be optional surgery patterns, especially modified Pearson operation.

PMID- 15566665
TI  - [Survivin expression in laryngeal squamous cell carcinoma and its relationship
      with clinical factors].
AB  - BACKGROUND & OBJECTIVE: Survivin, a new described member of the family of
      apoptosis inhibitory proteins (IAP), is undetectable in normal tissue of adults,
      but abundantly expressed in a variety of human malignancies. This study was
      designed to examine the expression of Survivin in laryngeal squamous cell
      carcinoma, analyze the relationships between the expression of Survivin and
      prognostic factors including age, gender, clinical stage, T stage, N stage,
      classification, histology and recurrence, to investigate its significance on
      prognosis. METHODS: Clinical information and paraffin- embedded tumor samples of
      81 cases laryngeal squamous cell carcinoma (LSCC) patients, who were treated at
      Cancer Center of Sun Yat-sen University between 1997 and 1998, were collected.
      Tissue chip was made, and SP method was performed to analyze Survivin expression
      in tumor tissue and adjacent normal laryngeal mucosa. SPSS 10.0 software was
      used. Kaplan-Meier method was used for survival analysis, and log-rank test was
      used for data analysis; multivariate analysis was carried out using Cox
      proportional hazard model. RESULTS: The overall 5-year survival rate for patients
      with laryngeal squamous cell carcinoma in this study was 58.33%. The over
      expression rate of Survivin in tumor tissue and adjacent normal laryngeal tissue
      were 50.62%, 0%, respectively (P< 0.05). The positive Survivin expression group(5
      year overall surivial rate: 22.06%) had a worse prognosis than that of negative
      group (5- year overall survival rate: 92.33%)(P< 0.05). The univariate analysis
      showed that clinical stage, T stage, N stage, histology grade, recurrence, and
      Survivin expression were the most important prognostic factors (P< 0.05). The
      Chi(2) test results showed that the expression of survivin was correlated with
      clinical stage, T stage, N stage, histology grade and recurrence (P< 0.05);
      Multivariate analysis results showed that clinical stage, survivin expression,
      and recurrence were independent prognosis factors on survival in LSCC patients.
      CONCLUSIONS: The expression of Survivin is an important biological factor
      affecting the prognosis; Tissue chip method can be simply and efficiently used in
      large scale of retrospective study in laryngeal squamous cell carcinoma.

PMID- 15566666
TI  - [Surgical treatment of well-differentiated thyroid carcinoma invading trachea: a
      report of 15 cases].
AB  - BACKGROUND & OBJECTIVES: At present head and neck surgeons from many countries
      have different opinions on management of well-differentiated thyroid cancer
      (WDTC). We will discuss WDTC invading trachea surgical treatment and its clinical
      significance. METHODS: Retrospectively reviewed clinical data of 15 cases WDTC
      invading trachea, According to WDTC invading extent and grade, there were 3 kinds
      of surgical approaches: 1) end to end anastomosis; 2) tissue flap reconstruction;
      3)larynx-tracheal dissociation. RESULTS: 15 cases underwent radical resection and
      reconstruct the defect of tracheal or larynx-tracheal dissociation. 2 cases
      received directly suture, 5 cases received sternocleidomastoid muscle flap
      reconstruction, 2 cases received pectorlis major muscle flap reconstruction, 2
      cases received platysma flap reconstruction, 2 cases received free forearm flap
      with muticore titanium-board reconstruction, 2 cases received larynx-tracheal
      dissociation with larynx block out and tracheal fistula. 10 cases (10/15, 66.7%)
      received decannulation postoperation. Patients who were success fully
      decannulated could recover phonation and maintain airway breath. In the 5
      patients who couldn't decannulate, underwent sternocleidomastoid muscle flap
      reconstruction, 1 underwent free forearm flap with muticore titanium-board
      reconstruction, 1 underwent pectorlis major muscle flap reconstruction, 2
      underwent larynx-tracheal dissociation, but all of them could hardly utter voice
      by compress tracheostoma and needed permanent tracheostoma due to collapse of
      trachea. The recurrence rate of our group is 33.33%, 5 years survival rate is
      88.89%. CONCLUSIONS: WDTC with trachea invading easily cause dyspnea or emptysis
      influencing on 5 years survival rate. We should take more actively surgical
      approach to resect all the tumor and involved organ, thus improve survival rate
      and reduce recurrence postoperation.

PMID- 15566667
TI  - [Clinical significance of human telomerase reverse transcriptase in patients with
      colon cancer].
AB  - BACKGROUND & OBJECTIVE: Although telomerase activity can be detected in 70%-90%
      malignant tumor tissues, it is still a controversial prognostic factor of
      patients with malignant tumors. This study was to evaluate clinical significance
      of human telomerase reverse transcriptase (hTERT) in patients with colon cancer.
      METHODS: Expression of hTERT in 59 matched pairs of tumor and adjacent non
      tumorous mucosa samples from patients with colon cancer who underwent complete
      resection were measured by quantitative real-time reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: Expression of hTERT in both tumor
      samples and nontumorous mucosa samples has no significant correlation with
      clinicopathologic factors. Of 32 patients with colon cancer of Dukes' A, and B
      stages, prognosis of 18 (56%) patients with hTERT expression of lower than 0.60
      in tumor tissue was better than that of 27 (44%) patients with hTERT expression
      of higher than 0.60 (P=0.006), prognosis of 20 (62%) patients with the value of
      hTERT expression in tumor tissue subtracted from that in matched non-tumorous
      tissue below 0.50 was better than that of 12 (38%) patients with that value above
      0.50 (P=0.035). In 27 patients with colon cancer of Dukes' C, and D stages, it
      was not practical to estimate the patients' prognosis with hTERT expression level
      in tumor tissue and the expression difference between tumor tissue and non
      tumorous tissue. CONCLUSION: hTERT expression may be a potential prognostic index
      for patients with colon cancer of Dukes' A, and B stages.

PMID- 15566668
TI  - [Long-term result of low anterior resection with stapling devices for rectal
      cancer].
AB  - BACKGROUND & OBJECTIVE: Currently, to preserve the anal function and improve the
      patients' quality of life, low anterior resection has become the preferred option
      in curative rectal cancer surgery. As the use of stapling instruments provides
      more reliable anastomoses in low anterior resection for rectal cancer, it
      enlarges the indication of this procedure. The aim of this study was to review
      the operation results and their outcomes of 449 rectal cancer patients who
      recieved of curative low anterior resections with stapling devices, and intent to
      find some measures that can reduce complications and improve long-term effects of
      this procedure. METHODS: The study included 449 patients who had a potentially
      curative anterior resection with stapled anastomosis in rectal cancer between
      Jan.1990 and Sept. 2002 at Sun Yat-sen University Cancer Center. All patients had
      complete follow-up data. All data were analyzed by SPSS8.0 software, risk factors
      for anastomotic leakage and recurrence were analyzed by Logistic regression,
      survival was analyzed by life table, and prognostic factors were screened by
      multivariate COX model. RESULTS: There were 11 cases of anastomotic leakage and
      23 cases of anastomotic recurrence after operation. The 5-year survival rate was
      78.4%. Age of >/= 65 years, and tumor involvement of more than half circumference
      were risk factors for anastomotic leakage, blood transfusion during operation was
      the risk factor for anastomotic recurrence. The independent factors for poor
      survival were stage of disease and tumor differentiation. CONCLUSIONS: Stapling
      devices can improve the anal reservation rate in low rectal cancer surgery, and
      stapled anastomoses is safe and feasible. Adequate preparation of bowel ends, a
      tension-free anastomosis with excellent blood supply and skilled stapled
      anastomoses were key measures to reduce anastomotic leakage, While TME,
      multidisciplinary therapy and the principle of avoiding medical spread, were key
      measures to improve treatment effect of rectal cancer.

PMID- 15566669
TI  - [Relationship between dihydropyrimidine dehydrogenase(DPD) activity and toxicity
      of 5-FU-based adjuvant chemotherapy in colorectal cancer patients].
AB  - BACKGROUND & OBJECTIVE: The efficacy and toxicity of 5-FU was various in
      different patients. It was reported that they were correlated to the activity of
      dihydropyrimidine dehydrogenase (DPD). This study is to measure DPD activity in
      blood and to analyze the relationship among DPD activity, the toxicity of 5-FU
      based adjuvant chemotherapy and the 5-FU plasma concentration in colorectal
      cancer patients. METHODS: 30 colorectal cancer patients were enrolled into the
      study to receive adjuvant chemotherapy 2 weeks after cured resection. The regimen
      was 5-FU 425 mg/m(2) plus CF 60 mg/m(2) continuous infused for 2 hours, daily for
      5 days. The concentration of endogenous uracil (U) and dihydrouracil (UH(2)) were
      assayed by high performance liquid chromatography (HPLC). The UH2-U ratio in
      plasma was used to represent DPD activity in blood. The plasma samples were
      collected before chemotherapy in all patients to detect the DPD activity in
      blood, and after 5-FU infusion at day 1 and day 5 to measure 5-FU plasma
      concentration. The relationship among the DPD activity in blood, the toxicity of
      chemotherapy and the plasma concentration of 5-FU in all patients were analyzed.
      RESULTS: 30 colorectal cancer patients have received adjuvant chemotherapy. The
      DPD activity in the blood of 30 colorectal cancer patients before chemotherapy
      was 4.09+/-1.21 (2.14-6.7), showed a trend of normal distribution. The 5-FU
      plasma concentration after 5-FU infusion was (2 079.12+/-621.41) microg/L (1
      200.10-3 554.80 microg/L) at the first day, and (2 197.64+/-606.78) microg/L at
      the fifth day (1 259.00-3 441.03 microg/L). There was a negative relationship
      between the DPD activity in blood and the 5-FU plasma concentration at day 1 (r=
      0.773, P=0.00), and day 5 after 5-FU infusion(r = -0.833, P = 0.00). No
      significant difference between the 5-FU plasma concentration of day 1 and day 5
      was found (P=0.458). The 5-Fu associated toxicities had a negative relationship
      with DPD activity in blood, and had a positive relationship with 5-FU plasma
      concentration (P< 0.05). CONCLUSION: The results indicated that the DPD activity
      in blood can be used to predict the toxicity and the 5-FU plasma concentration in
      patients with 5-FU based chemotherapy.

PMID- 15566670
TI  - [Initial results of intra-arterial chemotherapy for poorly differentiated bladder
      transitional cell carcinoma].
AB  - BACKGROUND & OBJECTIVE: Bladder cancer is the most common disease among
      urogenital tumors, and poorly differentiated bladder transitional cell carcinoma
      (BTCC) tends to recur, progress, and metastasize. This paper was to report our
      experiences in intra-arterial chemotherapy as adjuvant and palliative therapy for
      poorly differentiated BTCC. METHODS: Twenty-four patients with BTCC of grade 3
      were treated with intra-arterial chemotherapy of GC regimen (gemcitabine plus
      cisplatin). Among them, 21 had post-operative adjuvant intra-arterial
      chemotherapy for 3 cycles, 3 advanced cases had palliative intra-arterial
      chemotherapy for 6 cycles. RESULTS: All patients were followed-up for 6-20
      months. The mean follow-up was 12 months for 21 patients received adjuvant
      treatment, 1 developed pelvic metastasis, the others survived without evidenced
      tumors. Of 3 advanced cases, 1 with CR survived disease-freely for 8 months; 1
      with PR survived progression-freely for 6 months; 1 with PR died of tumor relapse
      13 months after chemotherapy. No serious complication was observed after intra
      arterial chemotherapy. CONCLUSIONS: Intra-arterial chemotherapy is effective in
      managing poorly differentiated BTCC.

PMID- 15566671
TI  - [Palliative surgery combined with oxaliplatin-based chemotherapy in treatment of
      patients with advanced gastric cancer].
AB  - BACKGROUND & OBJECTIVE: Gastric cancer has the highest incidence rate and
      mortality rate among gastrointestinal malignancies. Twenty percent of the
      patients with dissectable gastric cancer cannot be cured simply by surgery due to
      local infiltration and distant metastasis. To evaluate the therapeutic
      effectiveness and safety of oxaliplatin combined with 5-fluorouracil and
      leucovorin on the patients with gastric carcinoma after palliative gastric
      resection, we analyzed all of the cases of gastric adenocarcinoma undergone
      palliative gastric resection in our Cancer Center in recent years. METHODS: A
      total of 41 patients who underwent palliative gastric resection from Jan. 2000 to
      May 2004 in our Cancer Center were evaluated. Chemotherapy was given 8-18 days
      post-surgically with oxaliplatin (130 mg/m(2), intravenus infusion) on day 1,
      leukovorin (200 mg/m(2)) on day 1, 5-FU (500 mg/m(2), infusion) on day 1 followed
      by (5-FU 2600 mg/m(2), continuous infusion) for 48 h, the cycle was repeated
      every 4 weeks. Primary evaluation was performed after 3 cycles of chemotherapy.
      The chemotherapy was terminated in the patients without response to the
      treatment. In the patients with response to the treatment, the chemotherapy
      continued until 6-8 cycles for further analyses. RESULTS: None of the patients
      died from surgery or chemotherapy. Complete response occurred in 2 cases, partial
      response occurred in 19 cases, stable disease in 8 cases, and progressive disease
      in 12 cases. The total response rate was 52.5%. The 1-year, 2-year, and 3-year
      survival rates were 71%, 43%, and 32%, respectively. The side effects included
      neuropathy, nausea, vomiting, and myelosuppression. No grade 3 or 4
      myelosuppression was observed. CONCLUSION: Palliative surgery in late stage
      gastric cancer followed by combination chemotherapy of oxaliplatin, 5
      fluorouracil and leucovorin is a safe therapeutic modality with promising short
      term effectiveness and mild side effects.

PMID- 15566672
TI  - [Regulation for distribution of metastatic cervical lymph nodes of 512 cases of
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: To identify the target volume of radiotherapy is more and
      more important. This study was designed to explore the regulation for the
      distribution of metastatic cervical lymph nodes of nasopharyngeal carcinoma (NPC)
      and to recommend the delineation of clinical target volume of the neck for three
      dimensional conformal radiotherapy in NPC. METHODS: From Jan. 2003 to Jun. 2004,
      512 of cases of NPC, histologically diagnosed, received enhanced transversal CT
      scan. The cervical node was divided into six levels (I-VI) plus retropharyngeal
      nodes according to RTOG guidelines proposed in 2003. RESULTS: Of 512 patients,
      328 (64.1%) had cervical lymphadenopathy at presentation. Of the 328 neck
      positive cases, the node involvement was unilateral in 61.3% patient and
      bilateral in 38.7%. 328 (64.1%) cases showed enlargement of retropharyngeal node,
      and unilateral 50.9%, bilateral 49.1%. The involvement for levelIto level VI and
      retropharyngeal area in node-positive cases was 3.0%, 97.9%, 46.0%, 9.5%, 13.7%,
      0% and 74.4%. Of the node-positive patient, the incidence of skip metastasis was
      from 4.6% to 6.5%. 25.3% of the node-positive cases showed involvement, which is
      beyond CTV for the neck of stage N0 recommended by RTOG. CONCLUSIONS: The
      cervical node involvement of NPC is spread orderly down the neck, and the
      incidence of skip metastasis is lower. Retropharyneal node was the first echo
      node to metastases of NPC. The retropharyngeal node, level II, and level III were
      the most frequently involved area. Level Ia and level VI were never involved.
      There are few cases with positive nodes beyond CTV for the neck of stage N0
      recommended by RTOG. Our data is helpful for the delineation cervical target in
      the 3-D conformal radiotherapy of NPC.

PMID- 15566673
TI  - [Analysis of differences on delineation of the gross tumor volume (GTV) of
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Accurate delineation of tumor target volume and organ at
      risk based on CT simulation, is essential in modern radiotherapy planning. It is
      also the basic requirement to improve the treatment outcome and quality of life
      in nasopharyngeal carcinoma (NPC). In this study, the impact factors on
      delineation of the gross tumor volume (GTV) of NPC were analysis. by comparing
      difference among various doctors' contours. METHODS: Thirty cases of NPC
      treatment planning with contrast enhanced CT scan were reviewed. Primary GTV
      delineated by in-charged physician was defined as GTV1. Another GTV delineated by
      author and a radiologist was defined as GTV2, while GTV1 was concealed by the
      functions of the treatment planning system, the longest diameters of each axis of
      GTV were measured and recorded respectively as X(1), Y(1), Z(1), and X(2), Y(2),
      Z(2). The volumes of GTV were calculated as V1 and V2. Maximum permitted error
      (MPE) was 2 mm on X and Y axes and 3 mm on Z axis. Margin of each axis was
      compared to Coparable MPEs by matching t-test. RESULTS: The differences on axes
      of X, Y, Z between GTV1 and GTV2 were 2.95+/-4.33, 6.24+/-7.52, 6.25+/-9.35,
      respectively (P</=0.001). GTV1 was universally delineated too much, 33.33%(10/30)
      of them were over contour of air cavity. In all of the cases, at least difference
      in 1 site was found, while 19 cases had differences in 3 or more sites. However,
      one third was deficient on Z axis. CONCLUSION: The delineation of GTV of NPC
      varied by radiation oncologists remarkably. This should be taken into
      consideration as one of uncertainties in treatment planning designation. Further
      training of radiology for radiation oncologist to improve their imaging diagnosis
      ability and implementation of more advance imaging equipment are warranted.

PMID- 15566674
TI  - [Intensity modulated radiotherapy for local-regional advanced nasopharyngeal
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Local-regional uncontrolled is an important reason of
      treatment failure for advanced nasopharyngeal carcinoma (NPC) after radiotherapy.
      Local-regional control rate increased with dose to tumor target volumes. Because
      of the complex anatomy features, dose escalation using conventional two
      dimensional radiotherapy planning is limited by the tolerance of adjacent
      critical organs. In order to enhance doses to target volumes and local-regional
      control rates, this study explored application of intensity modulated radiation
      therapy (IMRT) in local-regional advanced NPC. METHODS: Sixty patients with naive
      primary NPC, 49 in stage III, and 11 in stage IVa, received IMRT alone with an
      inverse planning system (CORVUS 3.0, Peacock plan). Treatment was delivered with
      the Multi-leaf Intensity Modulating Collimator (MIMiC) using a slice-by-slice arc
      rotation approach. The prescription dose was 68 Gy to nasopharynx gross tumor
      volume (GTVnx), 60-64 Gy to positive neck lymph nodes (GTVnd), 60 Gy to clinical
      target volume I (Target I), and 54 Gy to clinical target volume II (Target II),
      delivered by 30 fractions. Acute normal tissue effects were graded according to
      RTOG/EORTC radiation morbidity scoring criteria. Local control rate, regional
      control rate, distant metastasis-free rate, and overall survival rate were
      calculated using Kaplan-Meier method. RESULTS: Analysis of dose-volume histograms
      (DVH) showed that the average mean dose delivered were 71.21 Gy to GTVnx, 65.85
      Gy to GTVnd(L), 66.26 Gy to GTVnd(R), 67.59 Gy to Target I, and 61.42 Gy to
      Target II. The mean fractional dosage delivered were 2.37 Gy to GTVnx, 2.20 Gy to
      GTVnd(L), and 2.21 Gy to GTVnd(R). The average volumes of all target volumes
      covered by 95% isodose were more than 99%, and the average volume of GTVnx
      covered by 105% isodose was 43.87%; 5% of brainstem volume, and 1cc of spinal
      cord volume received average dosage were 46.96 Gy, and 39.99 Gy; 33% of volume of
      bilateral parotids, and T-M Joints received average dose was less than 38 Gy.
      There was no Grade 4 acute toxicity in all patients, and incidences of acute
      grade 3 toxicity of skin, mucous membrane, and salivary glands were 1.7%, 15.0%,
      and 1.7%, respectively. With the median follow-up of 15.5 months (6-37 months),
      no patient failed at the primary site, 2 patients relapsed at neck, 7 patients
      developed distant metastases, 9 patients died. The 3-year local control rate,
      regional control rate, and distant metastasis-free rate were 96.67%, 94.06%, and
      84.98% respectively, 3-year overall survival rate was 74.97%. CONCLUSIONS: IMRT
      could escalate the total dose and fractional dosage to target volumes, and
      decrease the irradiation dose of surrounding critical organs. The acute
      toxicities were slight and tolerable. The local-regional control rates were
      satisfied. Distant metastasis is the main cause of failure.

PMID- 15566675
TI  - [Application of 18F-FDG PET/CT scan in following-up of nasopharyngeal carcinoma
      after radiotherapy].
AB  - BACKGROUND & OBJECTIVE: Local relapse,tumor residue, and whole body metastases of
      nasopharyngeal carcinoma (NPC) after radiotherapy were mainly confirmed by CT,
      MRI, SPE/CT, and PET examinations. This study was to discuss the value of F-18
      fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography
      (PET/CT) in detecting suspected recurrence or tumor residue, and whole body
      metastases of NPC after radiotherapy. METHODS: PET/CT were performed on 38 NPC
      patients 3-36 months after radiotherapy. The images of PET/CT, CT, and PET were
      observed. PET standardized uptake value (SUV) was calculated, and SUV of > 2.5
      was considered as positive. The Patients were divided into 4 groups by diagnosis:
      (1) no recurrence/residue, and no whole body metastases; (2) with
      recurrence/residue, but no whole body metastases; (3) no recurrence/residue, but
      with whole body metastases; (4) with both recurrence/residue and whole body
      metastases. Diagnoses of all patients were referred to the proved follow-up
      clinical information. The following-up time was 6-10 months. RESULTS: The
      sensitivity, and specificity of PET/CT (100%,and 89.5%) were better than that of
      CT alone (77.8%, and 84.2%), a litter better than that of PET alone (100%, and
      80.0%). CONCLUSIONS: FDG-PET scan is a better tool than CT alone for the
      detection of recurrene or residue, and whole body metastases of NPC, a litter
      better than PET alone. PET/CT may provide valuable information for judging
      whether the focus is metastasis.

PMID- 15566676
TI  - [Prognosis and treatment for 98 patients with carcinoma of nasal cavity].
AB  - BACKGROUND & OBJECTIVE: Carcinoma of nasal cavity is a rare disease without
      standard treatment. This study was designed to evaluate treatment outcome, and
      prognostic factors of patients with carcinoma of nasal cavity. METHODS: Records
      of 98 patients with carcinoma of nasal cavity were reviewed,43 patients received
      radiotherapy alone, 55 patients received surgery plus radiotherapy. Survival
      analysis was performed by Kaplan-Meier method,differences between groups were
      tested by log-rank test,multivariate analysis was carried out by Cox proportional
      hazard model. RESULTS: The overall 5-, and 10-year survival rates were 65.3%, and
      37.1%. The 5-, and 10-year survival rates of patients with tumor of stage I, II
      were 87.3%, and 51.1%, those of patients with tumor of stage III, IV were 56.1%,
      and 32.2% (P=0.02). The patients with squamous cell carcinoma had lower survival
      rates than those with adenocarcinoma (P< 0.01). There was significant difference
      in survival rates between patients received radiotherapy alone and patients
      received radiotherapy plus surgery in advanced lesions (P=0.04) and in squamous
      cell carcinoma (P< 0.01), but not in early lesions (P=0.41) and in adenocarcinoma
      (P=0.73). Patients who were initially diagnosed cervical lymph node metastasis
      had a reduced survival rate compared with node-negative patients (P=0.01). In
      Cox's regression, clinical stage and node-positive were independent prognostic
      factors. CONCLUSIONS: The criteria should be taken into account when choosing
      treatment method for patients with carcinoma of nasal cavity: radiotherapy plus
      surgery is preferred for advanced lesions and for squamous cell carcinoma,
      radiotherapy alone is better for early lesions and for adenocarcinoma. Clinical
      stage, and node-positive may be independent prognostic factors of patients with
      carcinoma of nasal cavity.

PMID- 15566677
TI  - [Prognostic analysis of 151 patients with maxillary sinus malignant neoplasms].
AB  - BACKGROUND & OBJECTIVE: Five-year survival rate of patients with maxillary
      malignant neoplasms is low, the prognostic factors of these neoplasms were
      unclear. This study was to investigate prognostic factors of maxillary sinus
      malignant neoplasms. METHODS: Records of 151 inpatients with malignant neoplasms
      of maxillary sinus initially treated at Cancer Center of Sun Yat-sen University
      from Sep. 1983 to Mar. 1999 were reviewed. Of 151 cases, 72 were squamous cell
      carcinoma (SCC), 44 were adenocarcinoma, 16 were sarcoma, and 19 were other
      histological types; according to 1997 UICC classification, 7 were stage II, 55
      were stage III, and 89 were stage IV; 66 patients received combined therapy of
      surgery and radiotherapy, 14 received surgery alone, 25 received radiotherapy
      alone, 39 received other treatments, and 7 gave up treatment. All patients were
      followed up for more than 5 years. Influences of clinicopathologic factors on
      prognosis of patients with maxillary sinus malignant neoplasms were analyzed by
      Kaplan-Meier method, and Cox regression model with SPSS10.0 software. RESULTS:
      Five-year overall survival rate of patients of </=40 years old was 55.7%, that of
      patients of >40 years old was 33.3%(P=0.030); that of patients with SCC was
      30.2%, of patients with adenocarcinoma was 57.5%, of patients with sarcoma was
      24.3%, of patients with tumor of other histological types was 50.7% (P=0.011);
      that of patients with tumor of stage II, III, and IV were 85.7%, 45.8%, and
      32.7%, respectively (P=0.029); that of patients with cervical metastases was
      14.4%, of patients without cervical metastases was 44.1% (P=0.005); that of
      patients with distant metastases was 14.3%, of patients without distant
      metastases was 41.1% (P=0.011); that of patients without treatment was 14.3%, of
      patients treated with surgery alone was 42.9%, of patients treated with
      radiotherapy alone was 32.3%, of patients treated with combined therapy of
      surgery and radiotherapy was 50.8%, of patients treated with other treatments was
      29.1% (P=0.004). Univariate survival analysis showed that the above 6 factors
      were prognostic factors of patients with maxillary sinus malignant neoplasms.
      Multivariate analysis showed that combination of surgery and radiotherapy
      (P=0.004, OR< 1), clinical stage (P=0.025, OR >1), SCC (P=0.016, OR >1), and
      sarcoma (P=0.003, OR >1) were independent prognostic factors of patients with
      maxillary sinus malignant neoplasms. CONCLUSION: For maxillary sinus malignant
      neoplasms, patients with SCC or sarcoma had poorer survival than patients with
      adenocarcinoma or other histological types of tumor; patients with sarcoma had
      poorer survival than patients with SCC. The higher the patient's clinical stage
      was, the worse his prognosis was. Combination of surgery and radiotherapy may be
      the best treatment for patients with maxillary sinus malignant neoplasms.

PMID- 15566678
TI  - [Expression of P53 and PCNA in nasopharyngeal carcinoma and their relation with
      clinical stage, VCA/IgA, EA/IgA, radiation sensibility, and pognosis].
AB  - BACKGROUND & OBJECTIVE: P53 and proliferating cell nuclear antigen(PCNA) relate
      with tumorigenesis, development, and prognosis of malignant tumors. This study
      was to detect expression of P53 and PCNA in nasopharyngeal carcinoma (NPC)
      tissue, and discuss their relation of p53 and PCNA expression with clinical
      stage, VCA/IgA, EA/IgA, radiation sensibility, and prognosis. METHODS:
      Immunohistochemistry was used to detect P53 and PCNA expression in NPC tissue of
      80 patients received radiotherapy alone. Relation of P53 and PCNA expression with
      clinical stage, VCA/IgA, EA/IgA, extinction of nasopharygeal tumor and neck lymph
      node when radiation dose was 36 Gy, and 5-year survival rate was analyzed by Chi
      square test. RESULTS: Positive rate of P53 in NPC tissues was 92.5%, and that of
      PCNA was 100%. Expression intensity of PCNA significantly related with extinction
      of nasopharygeal tumor, and neck lymph node when radiation dose was 36 Gy, but
      P53 had no significant relation with it. Expression intensities of P53 and PCNA
      had no significant relation with NPC clinical stage, VCA/IgA, EA/IgA, and 5-year
      survival rate. CONCLUSIONS: P53 and PCNA relate with NPC occurrence. PCNA relates
      with NPC radiation sensibility, but P53 doesn't. P53 and PCNA have no relation
      with NPC clinical stage, VCA/IgA, EA/IgA, and prognosis.

PMID- 15566679
TI  - [Individualized therapy and outcomes of microsurgery, radiotherapy, and
      chemotherapy for astrocytoma].
AB  - BACKGROUND & OBJECTIVE: Astrocytomas, constitute about 75% of neuroepithelial
      tumors, is one of the most common primary tumors in central nervous system with
      fairly high incidence and poor prognosis. Individualized multimodality is the
      hope for improving prognosis of patients with astrocytoma. This study was
      designed to investigate the efficiency of individualized treatment of
      microsurgery, radiotherapy, and chemotherapy for 62 patients with astrocytoma.
      METHODS: Sixty-two patients with astrocytoma in study group were treated with
      individualized multimodality of microsurgery, postoperative radiotherapy, and/or
      postoperative chemotherapy according to in vitro sensitivity assay. After
      microsurgery, 59 patients accepted radiotherapy, 46 patients received
      chemotherapy. Fifty patients with astrocytoma in control group were treated with
      conventional treatment of surgery, chemotherapy, and radiotherapy. After surgery,
      31 patients received radiotherapy following by BCNU chemotherapy, while 19
      patients accepted BCNU chemotherapy following radiotherapy. Pathologic diagnosis
      of patients in study group were 19 cases of grade, 32 cases of grade III, and 11
      cases of grade IV; in control group were 13 cases of grade II, 28 cases of grade
      III, and 9 cases of grade IV. Mean follow-up time were 25.8 months, and the
      outcome was evaluated by MRI, KPS, and survival rate. RESULTS: Tumor total
      resection rate in study group was 67.7%, while that in control group was 58.0%.
      There was no significant difference of KPS and survival rate in patients with low
      grade astrocytoma between 2 groups, while the outcome of patients with malignant
      astrocytoma was significantly improved by individualized treatment. In study
      group, 2-year expectant survival rate of patients with astrocytoma of grade III,
      and grade IV were 93.7%, and 36.3%, while in control group were 67.5%, and 22.2%
      (P< 0.05). In glioblastoma patients, median survival time of study group was
      18.68 months, while that of control group was 12.83 months (P< 0.01). CONCLUSION:
      Individualized microsurgery may improve the total resection of astrocytoma, and
      benefit to postoperative treatment.Individualized radiotherapy/chemotherapy may
      prevent patients from some complications. Individualized management may improve
      prognosis of patients with astrocytoma, particularly malignant astrocytoma.

PMID- 15566680
TI  - [Prognostic analysis of patients with cerebral glioma treated with radiotherapy].
AB  - BACKGROUND & OBJECTIVE: Surgery is the major treatment for glioma, and
      radiotherapy is often needed after operation. This study was to evaluate
      prognostic factors of patients with cerebral glioma treated with radiotherapy.
      METHODS: Records of 158 patients with cerebral glioma, including 123 patients
      with astrocytoma (AC), 12 patients with oligodendroglioma (OD) or mixed
      oligoastrocytoma (OA), and 23 patients with glioblastoma multiforme (GBM),
      received radiotherapy in our center were analyzed. Eighty patients received total
      resection, 77 received subtotal resection, and 1 received biopsy before
      radiotherapy. Median radiation dose was 58 Gy (36-75 Gy). Median waiting time
      from operation to radiotherapy was 29 days (12-261 days). Sixty-eight patients
      received chemotherapy before or after radiotherapy. Cox model was used for
      univariate and multivariate analysis. RESULTS: Median follow-up was 23 months (2
      62 months), 27 patients relapsed, and 57 patients died. The 2- and 4-year overall
      survival rate were 66.5% and 45.7%. Univariate analysis showed that histologic
      grade (I/II vs. II/IV), histologic type (AC/OD vs. GBM), Karnofsky performance
      state (KPS) before radiotherapy (>/=80 vs.< 80), extent of resection (total vs
      non-total), and age(</=40 years vs. >40 years) were significant predictors in
      association with overall survival rate of patients with glioma. Multivariate
      analysis showed that histologic grade (P=0.001), age (P=0.006), KPS before
      radiotherapy (P=0.009), and extent of resection (P=0.037) were independent
      prognostic factors of glioma. CONCLUSION: Low grade (I/II), age </=40 years,
      KPS>/=80 before radiotherapy, and total resection are independent factors for
      predicting better survival of glioma patients.

PMID- 15566681
TI  - [Clinical value of brachytherapy of malignant biliary obstruction after
      implanting expandable metallic biliary endoprothesis (EMBE)].
AB  - BACKGROUND & OBJECTIVE: For malignant biliary obstruction,drainage is the only
      procedure to cope with jaundice itself. It does not work for neoplasm. Patient
      will die of disease progress in a short time.With after-loading
      radiotherapy,radiofrequency ablation(RFA) and port catheter system(PCS)
      chemotherapy,we can directly apply these methods to treat neoplasm. This study is
      to investigate the value of after-loading treatment through biliary drainage and
      local chemotherapy embolism of PCS and RFA on treatment of malignant biliary
      obstruction after Expandable Metallic stent placement. Materials and Methods 49
      cases with malignant biliary obstruction can not or do not be suit for surgical
      treatment, including hepatic portal tumor 25 cases (17 with primary
      hepatocellular carcinoma,8 with metastasis carcinoma), biliary carcinoma 11
      cases, pancreatic carcinoma 6 cases, Clastkin tumor 7 cases. These patients were
      divided into four groups in random sampling. One underwent EMBE, the second
      underwent both EMBE and after-loading treatment,the third group underwent both
      EMBE and RFA, The last underwent both EMBE and PCS. EMBE of Percutaneous biliary
      drainage were placed in these patients first. The second group was given after
      loading treatment then. The third group was given RFA after EMBE. PCS were done
      in the last group. Chemotherapeutic agents were infused through PCS according to
      characteristics of biology and pharmacokinetics. RESULTS: 49 cases were
      successfully placed EMBE. In 49, 13 cases underwent EMBE, 16 cases underwent
      after-loading treatment after EMBE, 9 cases received RFA treatment, 11 cases
      underwent PCS after EMBE. Follow-up time was 1-12 months. For group EMBE: 6 cases
      (46.1%) developed re-obstruction in 1-3 months, 8 cases(61.5%)died in 2-6 months
      ,11 cases (84.6%)died in 12 months; for group after-loading:4 cases (25.0%)
      reobstructed in 1-3 months, 5 cases(31.25%) died in 2-6 months, 6 cases(37.5%)
      died in 12 months; for group EMBE and RFA: 2 cases (22.2%) reobstructed in 1-3
      months ,2 cases (22.2%) died in 2-6 months, 3 cases (33.3%) died in 12 months;for
      group EMBE and PCS:3 cases (27.27%) reobstructed in 1-3 months ,5 cases (45.45% )
      died in 2-6 months, 6 cases (54.54%) died in 12 months. The four groups have
      significant difference in reobstruction rate and mortality rate, by T-test (P<
      0.01). conclusion EMBE combined with brachytherapy is more effective methods than
      EMBE in treatment of malignant biliary obstruction.

PMID- 15566682
TI  - [MRI representations of glioma radioencephalopathy].
AB  - BACKGROUND & OBJECTIVE: Correctly distinguishing normal tissue reactive changes,
      tumor residue or relapse, and radioencephalopathy of glioma after radiotherapy by
      imaging methods is difficult. This study was to analysis MRI representations of
      glioma radioencephalopathy. METHODS: MRI records of 5 patients with golima
      radioencephalopathy treated in our hospital from Sept. 1998 to May 2004 were
      collected, 4 cases were confirmed by operation, and 1 was diagnosed by MRI and
      PET. All these 5 cases were suspected recurrence in MRI scans after 1 or 2
      radiotherapy periods, but them were confirmed radioencephalopathy pathologically
      after excision. RESULTS: MRI revealed all patients deteriorated within 40 days to
      7 months. The edema aggravated (5/5), and most were moderate or severe (4/5).
      Space occupying signs aggravated (5/5). Lesions enlarged (5/5) with irregular
      shapes like coral, map, or ring in enhanced scans. CONCLUSIONS:
      Radioencephalopathy of glioma occurs within 2 years after radiotherapy mostly.
      MRI scans manifest edema and space occupying signs aggravated, meanwhile the
      lesions enlarged progressively in a rather short time. It is characteristic that
      enhanced lesions were irregular and radiate.

PMID- 15566683
TI  - [Proteome analysis for identification of tumor-associated biomarkers in breast
      cancer].
AB  - BACKGROUND & OBJECTIVE: Pre-symptomatic screening of early-stage breast cancer
      may greatly reduce tumor-related mortality. Some tumor markers, such as CA15-3
      and CA27-29, are recommended only for monitoring therapy of advanced or relapsed
      breast cancer. This study was to find new biomarkers that could be used
      individually or in combination with an existing modality for cost-effective
      screening of breast cancer by proteome analysis. METHODS: Protein expression
      differences among 128 serum samples of 64 breast cancer patients (19 of stage I,
      24 of stage II, and 21 of stage III), 52 patients with benign breast diseases,
      and 12 healthy women were analyzed with IMAC3 and WCX2 Ciphergen ProteinChip
      Arrays. RESULTS: On WCX2 chip, a panel of 5 proteins (9 116, 8 905, 8 749, 9 470,
      and 9 692 Da) was selected based on their collective contribution to the optimal
      separation between breast cancer patients and both non-cancer patients and
      healthy women, and expression of another 2 proteins (9 405 and 6 424 Da) was
      different between patients with breast cancer of stage I and stage III. On IMAC3
      chip, a panel of 9 proteins (5 236, 7 823, 7 464, 5 213, 5 334, 5 064, 5 374, 7
      756, and 7 623 Da) was selected based on their collective contribution to the
      optimal separation between breast cancer patients and both non-cancer patients
      and healthy women, and expression of another 3 proteins (7 922, 4 641, and 5 910
      Da) was different between patients with breast cancer of stage I and stage III.
      CONCLUSION: Protein expression in breast cancer patients is different from that
      in both non-cancer patients and healthy women, and those proteins with different
      expression may be used as new biomarkers in breast cancer.

PMID- 15566684
TI  - [Clinical featares and treatment principles of appendix carcinoid tumor: a report
      of 13 cases].
AB  - BACKGROUND & OBJECTIVE: Appendix carcinoid tumor is a rare disease, and lack of
      classic clinical features. This study was to explore clinical characteristics and
      treatment principles of appendix carcinoid tumor. METHODS: Clinical data,
      surgical procedures, and prognosis of 13 patients with appendix carcinoid tumor
      received appendectomy from 1985 to 2000 in our hospital were analyzed
      retrospectively. RESULTS: The diagnosis was established through operation and
      pathology. Patients with appendix carcinoid tumor comprised 0.29% of 4483
      patients underwent appendectomy during the same period. The tumors were located
      at the tip and the middle of appendix in 12 patients(92.3%). The diameter of
      tumor in 12 patients(92.3%) was less than 2 cm. Single appendectomy was performed
      on 11 patients, right-side colonectomy was performed on 2 patients. Nine patients
      were alive and remained free of tumor recurrence and metastasis, 3 were lost of
      follow up, and 1 died of heart disease. The 5-year survival rate is 100%.
      CONCLUSIONS: Appendix carcinoid tumor has no specific clinical symptom, and
      located at the tip and the middle of appendix; tumor with diameter of < 1 cm may
      be resected by single appendectomy.

PMID- 15566685
TI  - [Value of transvaginal color Doppler flow imaging conjugated with multiple serum
      tumor markers in diagnosis of ovarian tumors].
AB  - BACKGROUND & OBJECTIVE: To investigate the value of trasvaginal color Doppler
      flow imaging (TV-CDFI ) in combination with multiple serum tumor markers in the
      diagnosis of ovarian tumors. METHODS: A total of 74 patients with pelvic masses (
      30 cases with benign tumors, 44 cases with malignant tumors) were examined by TV
      CDFI and the level of 7 serum tumor markers was also measured at same time. The
      above results were compared with the pathologic findings. RESULTS: The diagnostic
      accuracy for the TV-CDFI only, and 7 serum tumor markers measured were 90.5% and
      59.5% respectively. If TV-CDFI combined with multiple serum tumor marker
      measurements, the diagnostic accuracy of 98.6% was achieved, whereby it was 97.7%
      for malignant tumors. CONCLUSION: TV-CDFI allows the diagnosis and differential
      diagnosis of the majority of ovarian tumors, particularly in part of ovarian
      carcinoma at early stage. Combined with multiple serum tumor marker measurements,
      this method can improve diagnostic sensitivity and specificity,hence it
      facilitates the early diagnosis and differential diagnosis.

PMID- 15566686
TI  - [Affecting factors of quality of life of colostomy patients].
AB  - BACKGROUND & OBJECTIVE: This study was to identify the factors that affect the
      quality of life (QOL) and bring forward methods of improving the QOL of colostomy
      patients, so as to offer evidences for practical nurses. METHODS: A descriptive,
      correlative design was employed in this study. From October, 2002 to February,
      2004, 86 colostomy patients who discharged from Tumor Hospital of Sun Yat-sen
      University were recruited to complete a series of questionnaires, including EORTC
      QLQ-C30, Symptom Check List(SCL-90), Perceived Social Support Scale(PSSS). The
      SPSS11.0 was used for data analysis. RESULTS: The QOL of colostomy patients was
      relatively low. The mean score of EORTC QLQ-C30 was 49.13+/-17.20. The score of
      QOL was negatively correlated with the score of SCL-90 and positively correlated
      with the score of social support. The score of SCL-90 was the most important
      factor that affected the QOL, followed by the income of the patients. CONCLUSION:
      The major factors affecting the QOL were mental health status, financial status
      and social support of the patients. The results point out practical nurses should
      keep an eye on these factors.

PMID- 15566687
TI  - Effect of environment on extremely severe road traffic crashes: retrospective
      epidemic analysis during 2000-2001.
AB  - OBJECTIVE: To make an epidemiological analysis of the effect of environment on
      extremely severe road traffic crashes (RTCs). METHODS: Epidemiologic data of
      extremely severe RTCs associated with environmental factors, including weather,
      topography, road conditions and other traffic conditions in Mainland China during
      2000-2001, were collected and analyzed. RESULTS: (1) During 2000-2001, there were
      3365 extremely severe RTCs with 13666 deaths, 12204 injuries and a direct
      economical loss of 136 million RMB. (2) Most extremely severe RTCs occurred in
      fine weather days and in the daytime. The high occurrence sites were plain areas,
      horizontal and straight roads, Grade B and C roads, ordinary road segment, and
      asphalt, smooth and mixed roads. (3) Compared with other RTCs, extremely severe
      RTCs were more likely to happen under following conditions: on cloudy, snowing,
      misty and blustering days; in hill and mountainous areas; on crooked and sloping
      roads; on freeway, Grade A, B, and C roads; mixed roads; ordinary, bridge, narrow
      and transitional roads; sand and dirt-roads; without traffic control measures;
      night without lighting. (4) Extremely severe RTCs of mountainous area or crooked
      and sloping roads were most severe in terms of deaths and injures per crash.
      CONCLUSIONS: Extremely severe RTCs are closely related with environmental
      factors. Rational road programming, enhancing road establishment and improving
      road conditions are probably effective measures to reduce the road traffic
      injuries.

PMID- 15566688
TI  - Gene expression profile of degenerated cervical intervertebral disc tissues in
      rats.
AB  - OBJECTIVE: To analyze the gene expression profile of degenerated cervical
      intervertebral disc of Sprague Dawley rats on a large scale. METHODS: Degenerated
      models of Sprague Dawley rats of 9 months old (degeneration group, n=9) and
      normal Sprague Dawley rats of 3 months old (control group, n=9) were prepared,
      respectively. mRNA was obtained from the cervical intervertebral disc of rats in
      both groups, respectively, and then labelled by Cy5 and Cy3 fluorescence
      respectively after reverse transcription to obtain intervertebral disc cDNA
      probes. cDNA probes were hybridized with BiostarR-40s gene expression profile
      chips and scanned by laser scanner. The results were treated with portrait
      analysis, standardization management, and ratio analysis with softwares. RESULTS:
      Compared with the rats in the control group, 9.6% (381 pieces in total) gene
      expression changed obviously in the rats in the degeneration group, among which,
      the gene expression quantities of 171 pieces increased significantly (r=the ratio
      of the degeneration group to the control group>2.0), 52 pieces of which had
      certain function. While the gene expression quantities of 211 pieces decreased
      significantly (r<0.5), 41 pieces of which had certain function. CONCLUSIONS: Gene
      chip technology can be used to analyze the gene expression profile of degenerated
      intervertebral disc of rats in parallel, in quantity and on a large scale, which
      helps to testify the representative genes and protein expression, and plays an
      important role in clarifying the pathogenesis of degenerated intervertebral disc.

PMID- 15566689
TI  - Effect of arousal methods for 175 cases of prolonged coma after severe traumatic
      brain injury and its related factors.
AB  - OBJECTIVE: To determine the effect of arousal methods for prolonged coma of 175
      patients with severe traumatic brain injury and related factors. METHODS: There
      were 175 cases with persistent coma longer than 1 month after severe traumatic
      brain injury. Coma lasted 1-12 months. Arousal procedures included hyperbaric
      oxygen, physical therapy and arousal drugs. RESULTS: In the 175 prolonged coma
      patients 110 got recovery of consciousness; in 118 cases with coma of 1-3 months,
      86 cases recovered consciousness (72.9%); in 42 cases with coma of 4-6 months, 20
      cases recovered consciousness (47.6); and in 15 cases with coma of longer than 6
      months, only 4 cases recovered consciousness (26.7%). The recovery of
      consciousness depended on patient's primary brain stem damage, cerebral hernia,
      GCS score, and age. CONCLUSIONS: Application of appropriate arousal procedures
      improves recovery of consciousness in patients with prolonged coma.

PMID- 15566690
TI  - The first metatarsal web space: its applied anatomy and usage in tracing the
      first dorsal metatarsal artery in thumb reconstruction.
AB  - OBJECTIVE: To clarify the anatomical relationship of the structures in the first
      toe webbing space for better dissection of toes in thumb reconstruction. METHODS:
      The first dorsal metatarsal artery, the first deep transverse metatarsal ligament
      and the extensor expansion were observed on 42 adult cadaveric lower extremities.
      Clinically the method of tracing the first dorsal metatarsal artery around the
      space of the extensor expansion was used in 36 cases of thumb reconstruction.
      RESULTS: The distal segments of the first dorsal metatarsal artery of Gilbert
      types I and II were located superficially to the extensor expansion. The
      harvesting time of a toe was shortened from 90 minutes to 50 minutes with 100%
      survival of reconstructed fingers. CONCLUSIONS: The distal segment of the first
      dorsal metatarsal artery lies constantly at the superficial layer of the extensor
      expansion. Most of the first metatarsal arteries of Gilbert types I and II can be
      easily located via the combined sequential and reverse dissection around the
      space of the extensor expansion.

PMID- 15566691
TI  - A long-term follow-up study of high tibial osteotomy for medial compartment
      osteoarthrosis.
AB  - OBJECTIVE: To observe the long-term outcome of high tibial osteotomy (HTO) in
      treating medial compartment osteoarthrosis of knees. METHODS: A retrospective
      study was carried out on 194 patients (215 knees) treated with HTO for medial
      compartment osteoarthritis at the Orthopaedic Hospital of Kiel University between
      1985 and 1996. RESULTS: One hundred and sixty-one knees (144 patients) were
      followed up for 1.5-12 years with an average of 7.5 years and their data were
      reviewed. The proportion of excellent outcome were 97.3%, 93.6% and 78.2% two,
      five and over five years after HTO, respectively. The revision rate of total knee
      arthroplasty (TKA) was 11.8% (19 knees retreated with TKA for HTO failure). The
      survivorship analysis of the 19 knees retreated with TKA showed an expected
      survival rate of 98.7%, 95.0% and 84.1% 2, 5 and 10 years after HTO,
      respectively. There were 5.6% complications (12/161), including five superficial
      wound infections, one deep infection, five delayed bone healing, and one peroneal
      nerve palsy. Fifty patients (54 knees) missed follow-up, among them 10 patients
      (11 knees) died. CONCLUSIONS: HTO is an effective method in treating medial
      compartment osteoarthritis with a varus knee. Appropriate overcorrection of
      femorotibial alignment is the key for the success of the operation. But as the
      long-term effect is concerned, there is a trend of deterioration and some of the
      patients may have a second operation of revision with TKA.

PMID- 15566692
TI  - Pedicle screw fixation with translaminar facet joint screws for the treatment of
      thoracolumbar fracture.
AB  - OBJECTIVE: To evaluate the efficacy of Cotrel-Dubeusset (CD) instrumentation
      combined with translaminar facet joint screw (TLS) in the treatment of
      thoracolumbar fracture. METHODS: A total of six L(2)-L(4) spines were used to
      establish unstable fracture model with three-dimensional range of motion (ROM) of
      the spines measured. Fixation with CD and fixation with CD combined with
      translaminar facet joint screw were achieved to compare their stability. Thirty
      cases of thoracolumbar fracture, in whom the anterior edge of vertebral body was
      compressed to 59% and the posterior edge compressed to 88%, were treated by
      pedicle screw fixation combined with TLS. Among them, 19 received posterolateral
      or anterior-posterior bone grafting. RESULTS: There was significant difference in
      ROM between the two techniques except that in extension. In Group CD+TLS, ROM was
      5.38% lower, lateral bending 4.91% lower and axial rotation 11.85% lower than
      those in Group CD respectively. In the clinical group, the average anterior edge
      restored to 97% and posterior edge to 98%. The duration of follow-up was 5-24
      months (mean, 10 months). The rate of correction loss on the anterior edge was
      4.5%. Among the 19 cases of bone grafting, all of them achieved bony fusion (mean
      fusion time, 4.3 month) with a correction loss rate of 3.4%. CONCLUSIONS: In the
      treatment of thoracolumbar fracture, pedicle screw fixation combined with TLS can
      strengthen the stability of pedicle screws, especially anti-rotation stability
      and enhance fusion rate and reduce correction loss.

PMID- 15566693
TI  - Effect of type I collagen on the adhesion, proliferation, and osteoblastic gene
      expression of bone marrow-derived mesenchymal stem cells.
AB  - OBJECTIVE: To investigate the effects of porous poly lactide-co-glycolide (PLGA)
      modified by type I collagen on the adhesion, proliferation, and differentiation
      of rabbit marrow-derived mesenchymal stem cells (MSCs). METHODS: The third
      generation MSCs isolated from mature rabbits by density gradient centrifugation
      were cultured at different initial concentrations on 0.3 cm x 1.2 cm x 2.0 cm 3-D
      porous PLGA coated by type I collagen in RPMI 1640 containing 10% fetal calf
      serum, while cultured on PLGA without type I collagen as control. The cells
      adhesive and proliferative behavior at 7, 14, and 21 days after inoculation was
      assessed by determining the incorporation rate of [(3)H]-TdR. In order to examine
      MSCs differentiation, the expression of osteoblasts marker genes, osteocalcin
      (OCN), alkaline phosphatase (ALP), osteopontin (OPN) mRNA, were evaluated by
      reverse transcription-polymerase chain reaction (RT-PCR), and further more, the
      cell morphology at 21 days was also observed by scanning electron microscope
      (SEM). RESULTS: Type I collagen promoted cell adhesion on PLGA. The valve was
      significantly higher than controls (6 h, 2144 cpm+/-141 cpm vs. 1797 cpm+/-118
      cpm, P=0.017; 8 h, 2311 cpm+/-113 cpm vs. 1891 cpm+/-103 cpm, P=0.01). The cells
      which cultured on PLGA coated with type I collagen showed significantly higher
      cell proliferation than controls on the 7 th day (1021 cpm+/-159 cpm vs. 451
      cpm+/-67 cpm, P=0.002), the 14th day (1472 cpm+/-82 cpm vs. 583 cpm+/-67 cpm,
      P<0.001) and 21 th day (1728 cpm+/-78 cpm vs. 632 cpm+/-55 cpm, P<0.001).
      Osteoblasts markers, OCN, ALP, OPN mRNA, were all detected on PLGA coated by type
      I collagen on the 21 th day, but OCN, OPN mRNA could not be found in controls.
      Spindle and polygonal cells well distributed on the polymer coated by type I
      collagen while cylindric or round cells in controls. CONCLUSIONS: Type I collagen
      is effective in promoting the adhesion, proliferation and differentiation of MSCs
      on PLGA.

PMID- 15566694
TI  - Effect of Shenfu Injection (ginesenoside and aconite alkaloid) on the apoptosis
      of intestinal mucosal epithelial cells and its mechanism during ischemia
      reperfusion in rats.
AB  - OBJECTIVE: To investigate the effect of Shenfu Injection (SF, ginesenoside and
      aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells during
      ischemia-reperfusion in rats and its potential mechanisms. METHODS: Ischemia
      reperfusion model was established in rats. Twenty-four rats were divided into 3
      groups with 8 rats in each, eg, ischemia-reperfusion (I/R) group, SF-treated
      group, and control group. In both SF and I/R groups, the superior mesenteric
      artery was closed with forceps for 1 hour and then reperfused for 2 hours. Either
      SF (3 ml/kg, SF group) or normal saline (I/R and control groups) was injected
      intravenously and continuously for 5 ml/kg with a micropump before the superior
      mesenteric artery was closed. The superior mesenteric artery was not closed for
      animals in control group. The expression of casapse-3 and Fas, and the level of
      TNF-alpha and pathological changes of the ileal mucosal tissue were assayed.
      RESULTS: (1) The number of apoptosis cells increased obviously in I/R group and
      was significantly higher than that in SF and control groups (P<0.05). (2) The
      expression of caspase-3, Fas, and TNF-alpha was significantly higher in I/R group
      than SF and control groups (P<0.01); however, there was not significant
      difference in the expression of capase-3 between control group and SF group.
      There was a positive correlation between the expression of caspase-3, Fas, and
      TNF-alpha, and the number of apoptosis cells. (3) Under light microscope,
      intestinal mucosal impairment was found milder in SF group than I/R group
      (P<0.05). CONCLUSIONS: SF can depress the apoptosis of intestinal mucosal
      epithelial cells during ischemia-reperfusion by restraining the expression of TNF
      alpha, Fas, caspase-3, and accordingly alleviate the ischemia and reperfusion
      injury of intestinal mucosal epithelial cells.

PMID- 15566695
TI  - Protective effects of hypovolemic hypotension preconditioning on cardiopulmonary
      function after myocardium ischemia/reperfusion injury.
AB  - OBJECTIVE: To identify the protective effects of hypovolemic hypotension
      preconditioning on cardiopulmonary function after myocardial ischemia/reperfusion
      injury and to explore the possible mechanism. METHODS: Twenty-four male white
      rabbits were randomly assigned to two groups. In the control group,
      ischemia/reperfusion animals(Group I/R, n=10) were subjected to thirty-minute
      occlusion of left anterior descending coronary artery and two-hour reperfusion.
      Animals in hypovolemic hypotension preconditioning group (Group HHP, n=14)
      experienced brief systemic ischemia preconditioning through blood withdrawal to
      lower blood pressure to 40%-50% of the baseline before myocardial
      ischemia/reperfusion. Hemodynamic parameters were recorded. Blood sample was
      taken to measure superoxide dismutase (SOD), malondialdehyde (MDA) and nitrogen
      monoxide (NO) changes with blood gas analysis. Myocardium specimens were sampled
      to examine apoptosis-related gene interleukin-1 beta converting enzyme (ICE)
      mRNA. RESULTS: Cardiac mechanical function and lung gas exchange remained stable
      in Group HHP with a significant increase in NO level; while in Group I/R without
      preconditioning, cardiopulmonary dysfunction was present after 2 h reperfusion
      associated with a significant reduction in NO formation and an increase in MDA
      (P<0.001). There was negative expression of ICE mRNA in the two groups.
      CONCLUSIONS: Hypovolemic hypotension preconditioning significantly improves
      cardiopulmonary function and increases NO formation and the protective benefit
      associated with hypovolemic hypotension preconditioning of the heart may be
      regulated through NO mediated mechanism.

PMID- 15566696
TI  - Observation and establishment of an animal model of tractive spinal cord injury
      in rats.
AB  - OBJECTIVE: To establish an animal model of tractive spinal cord injury in rats in
      order to investigate its pathophysiological changes and clinical significance.
      METHODS: T(12)-L(3) spines were tracted longitudinally with a special spinal
      retractor that was put on the proccessus transverses of T(12)-L(3) vertebrae of
      the rat after exposing T(13)-L(2) spinal cord via dual laminectomy. At the same
      tine, the spinal cord function was monitored by cortical somatosensory evoked
      potential (CSEP). Rats were randomly divided into four groups according to the
      amplitude of CSEP P(1)-N(1) wave, the amount of the decreasing P(1)-N(1) wave was
      30% (the 30% group), 50% (the 50% group) and 70% (the 70% group), respectively.
      After traction, the changes of the neural behavioral function in rats were
      observed and the morphological structure of the spinal cord was analyzed
      quantitatively with image analysis system of computer. RESULTS: With traction of
      spine, compared with the control group, the 30% group had no marked difference in
      combined behavioral score (CBS), neuron count, section area of neuron and Nissl
      body density, but the 50% and 70% groups had marked difference (P<0.01). Light
      microscope showed that the neuron volume was slightly small and the Nissl body
      was reduced lightly in the 30% group; the neuron space was enlarged and the
      neuron was degenerative, reductive, and dissolved, and the spinal cord structure
      was destroyed in the 50% and 70% groups. CONCLUSIONS: The animal model of
      tractive spinal cord injury in rats is a reproducible, graded and clinic mimic.
      The model in this article provides a valuable assistance in further understanding
      etiopathology and screening effective measures of therapy and prophylaxis of the
      injury.

PMID- 15566697
TI  - Clinical analysis of 28 children suffering from intracranial hematoma and
      multiple injuries following traffic accidents.
AB  - OBJECTIVE: To evaluate the result of diagnosis and treatment of intracranial
      hematoma and multiple injuries caused by road traffic accidents. METHODS: Twenty
      eight patients, aged from 1 to 14 years, receiving craniotomy and other surgical
      treatments were retrospectively reviewed. RESULTS: Among the 28 cases, 23 cured
      with the recovery rate of 82.3%, 2 had a sequel of moderate disability, and 3
      died from severe brain injury, hemorrhagic shock, and other visceral
      complications. The clinical symptoms and signs were severe and perplexing. The
      major characters included: severe head injury, usually combined by multiple
      injuries, and easy of access to missed diagnosis and misdiagnosis. CONCLUSIONS:
      The occurrence of infection is high after traffic accidents as a result of
      depression of humoral and cellular immunity, long-term bed rest, and fractures of
      limbs. Hence, on the basis of maintaining vital signs, the management of primary
      wound is essential to reduce infection and underlying death. In addition to the
      management of brain injury, concurrent injuries should also be highlighted so as
      to reach a good result for their patients.

PMID- 15566698
TI  - Treatment for severe craniocerebral trauma combined with transtentorial hernia in
      children.
AB  - OBJECTIVE: To explore the treating method for severe craniocerebral trauma
      combined with transtentorial hernia in children. METHODS: We treated 58 children
      with severe craniocerebral trauma combined with transtentorial hernia through
      evacuating the hematomas, incising the tentorium but preserving the floating bone
      flap between January 1996 and January 2002. RESULTS: GCS was 3-5 in 17 cases and
      6-8 in 41 cases. After treatment, 46 patients (79.30%) recovered well, 6 (10.30%)
      suffered from mild disability, 1 (1.72%) suffered from severe disability, 1
      (1.72%) was in vegetative state, and 4 (6.90%) died. CONCLUSIONS: Evacuating
      hematomas and incising tentorium can effectively treat the child patients with
      severe craniocerebral trauma combined with transtentorial hernia, which can
      decrease the disability and mortality rates greatly, preserve the skull, exempt
      reoperation for cranioplasty and relieve the psychologic and physiologic burden
      of the child patients.

PMID- 15566699
TI  - Surgical treatment of superficial peroneal neuroma.
AB  - BACKGROUND: Several techniques have been described for the surgical treatment of
      symptomatic superficial peroneal neuromas, including transection of the nerve
      with burial in muscle or bone to prevent recurrence. METHODS: We compared in 27
      consecutive patients the results of transection and burial of the proximal
      peroneal nerve stump into muscle (group A) with results of transection and burial
      of the proximal stump into bone (group B). RESULTS: The perceived pain relief and
      improvement in mean pain score were significantly higher (p < .05) in group B
      than in group A. In addition, four patients in group A required revision
      neurotomy compared to none in group B. CONCLUSION: For symptomatic superficial
      peroneal neuromas, transection with transposition of the proximal nerve stump
      into bone provides superior results compared with those of neurotomy with
      transposition of the proximal stump into muscle.

PMID- 15566700
TI  - The management of concomitant tears of the peroneus longus and brevis tendons.
AB  - BACKGROUND: Concomitant chronic tears of both peroneal tendons rarely are
      reported. We present our experience in treating these injuries and suggest an
      algorithm for surgical treatment, determined by the presence of a functioning
      tendon or tendons, mobility of the remaining peroneal musculature, ankle
      stability, and position of the heel. METHODS: Twenty-eight consecutive patients
      (29 feet) were followed postoperatively for a mean of 4.6 (range 1.5 to 8) years.
      The mean age was 36 (range 19 to 54) years, and all patients had chronic ankle
      pain with or without instability and with combinations of complete, partial, or
      longitudinal tears of both tendons. Of the 28 patients, six had hindfoot varus
      and three had cavovarus. Eight patients had mechanical ankle instability, but
      there was no correlation between instability and the presence of hindfoot varus.
      RESULTS: The mean postoperative American Orthopaedics Foot and Ankle Society
      ankle score was 82 (range 20 to 100) points, and 91% of patients achieved normal
      or moderate peroneal muscle strength. Ankle instability was successfully
      corrected in all patients and progressive worsening of varus deformity was
      prevented. CONCLUSION: The presence of chronic peroneal tendon subluxation or
      dislocation, chronic ankle instability, or hindfoot varus deformity, in
      association with retrofibular pain and swelling, should alert the surgeon to the
      possibility of a tear of the peroneal tendons and is an indication for surgical
      intervention. At the time of tendon repair, every effort should be made to treat
      the primary or contributing causes of the tear. Our results suggest that patients
      with symptomatic concomitant peroneus longus and brevis tendon tears are likely
      to experience substantial improvement in function if operative treatment is
      adequate.

PMID- 15566701
TI  - Comparison between manual and computer-assisted measurements of hallux valgus
      parameters.
AB  - BACKGROUND: The aim of this study was to determine if there are intraobserver and
      interobserver differences in reliability when measuring hallux valgus angles
      (HVA), 1-2 intermetatarsal angles (IMA), and distal metatarsal articular angles
      (DMAA) manually compared to computer-assisted means. Our hypothesis was that the
      measurements taken by computer-assisted methods of these three forefoot angles
      would be superior in consistency and accuracy compared to manual measurements.
      METHODS: Four examiners studied 20 weightbearing anteroposterior radiographs of
      patients with hallux valgus. Manual measurements were taken on photographic
      prints using a goniometer and a fine point pen. Computer-assisted measurements
      were taken on digitized images using computer software. Three sets of
      measurements by both of these methods were taken 1 week apart. RESULTS: There was
      no statistically significant difference between digital and manual measurements
      for any of the three angles measured (p .05). However, the reliability of
      measurements within a range of 5 degrees for both methods was 70.6% for HVA, 84%
      for 1-2 IMA, and 59% for DMAA. CONCLUSION: There were no significant differences
      in interobserver and intraobserver reliability in measuring 1-2 IMA and HVA,
      regardless of the method of measurement; however, there was a significant
      difference in interobserver reliability when measuring the DMAA either on
      computer or manually (p = <.05).

PMID- 15566702
TI  - Strength and knot security of braided polyester and caprolactone/glycolide
      suture.
AB  - BACKGROUND: Appropriate suture selection is necessary in providing mechanical
      stability to soft tissue reconstructions. Caprolactone/glycolide (Panacryltrade
      mark) became a popular suture, possessing excellent handling properties; however,
      clinical observations questioned the knot security of caprolactone/glycolide.
      Caprolactone/glycolide is still available on many commercial suture anchor
      systems. This study compared the security of the knots and ultimate tensile
      strength of braided caprolactone/glycolide suture to that of a commonly used
      suture material, braided polyester (Ethibondtrade mark). MATERIALS: Suture knots
      of No. 2 braided polyester suture and No. 2 braided caprolactone/glycolide suture
      were submersed in a physiologic saline solution and stressed using a continuous
      (non-cyclic) load, simulating a single maximal loading event in a clinical
      setting. Continuous loading was done to achieve clinical suture knot failure (3
      mm knot slippage), then continued until catastrophic suture failure (suture
      breakage) occurred. Ten trials of each suture were tested. RESULTS: Force
      required to cause knot slippage of 3 mm was greater for braided polyester than
      for braided caprolactone/glycolide (p <. 0001, unpaired Students' t-test). Forces
      resulting in catastrophic failure were greater for braided polyester than braided
      caprolactone/glycolide (p = .0284, unpaired Students' t-test). CONCLUSIONS: These
      data have important implications in the selection of suture materials for repair
      of soft tissue injuries. In the clinical setting, a single maximal loading event
      may result in suture failure. These data indicate that braided polyester
      possesses superior in-vitro mechanical properties and suggest that braided
      polyester may provide greater security in-vivo than braided
      caprolactone/glycolide suture.

PMID- 15566703
TI  - Trimalleolar fractures with impaction of the posteromedial tibial plafond:
      implications for talar stability.
AB  - BACKGROUND: Trimalleolar fractures usually include a lateral malleolar fracture,
      a triangular fracture of the posterolateral corner of the tibial plafond, and a
      horizontal or oblique fracture of the medial malleolus. A subtype of a
      trimalleolar fracture is reported, differing in the shape and extent of the
      medial malleolar fracture and the posterior lip fracture, with implications for
      treatment. METHODS: In a 3-year period, 10 patients were treated for a
      trimalleolar fracture with a multifragmentary transverse fracture of the entire
      posterior tibial lip, including the posterior colliculus of the medial malleolus.
      The radiographs of all patients showed a pathognomonic double-contour or flake
      fragment sign above the medial malleolus. One patient's posteromedial fracture
      was not initially recognized and he had a standard lateral fracture repair. A
      double posterior approach was used in nine patients, with fracture repair
      proceeding from medial to lateral. Intraoperatively, eight of nine patients had
      impacted osteochondral fragments at the posteromedial corner of the tibial
      plafond that blocked anatomic reduction and allowed posteromedial subluxation of
      the talus. RESULTS: Nine patients had anatomic reconstruction of the
      posteromedial corner. All fractures healed, and function was normal at one year.
      One patient had moderate loss of joint space. The patient with the malunited
      fracture developed symptomatic posteromedial instability of the talus and
      required an osteotomy of the malunited fragment. He had a good result at 18
      months. CONCLUSIONS: This unique subtype of trimalleolar fracture has distinct
      radiological features and implications for the strategy of the operative
      treatment. If recognized immediately and treated appropriately, the results were
      excellent. If missed initially, reconstructive osteotomy was possible and led to
      a good result.

PMID- 15566704
TI  - The obliquity of the first metatarsal base.
AB  - BACKGROUND: The degree of obliquity of the base of the first metatarsal is
      thought to predispose to metatarsus primus varus deformity. Radiographs currently
      are used to interpret the obliquity of the proximal first metatarsal but are
      subject to error. A 'normal' obliquity of the first metatarsal base has not yet
      been established. METHODS: Direct measurements of 77 human first metatarsals were
      used to establish mean values for the proximal first metatarsal obliquity angle
      with respect to age, gender, and ethnicity in this sample population. The overall
      length of the first metatarsal and the width of the base were measured. The
      measured values were compared in relation to age, gender, and ethnicity of the
      specimens. RESULTS: The overall mean obliquity angle was 3.42 degrees (range, -3
      to 8 degrees, SD 2.54). The mean obliquity angle in females was 3.67 degrees
      (range, -3 to 8 degrees, SD 2.91). The mean obliquity angle in males was 3.30
      degrees (range, -2 to 7 degrees, SD 2.24). Mean base obliquity angle in the
      African-American specimens was 3.0 degrees (range, 3 to 7 degrees, SD 2.59),
      while the average first obliquity angle in the Caucasian specimens was 3.83
      degrees (range, -2 to 8 degrees, SD 2.34). The obliquity of the first metatarsal
      base increased with age from a mean of 3.5 degrees in the youngest group to 5.13
      degrees in the oldest. CONCLUSIONS: Exaggerated obliquity of the first metatarsal
      base is a proposed cause for metatarsus primus varus. No average values had been
      established for the proximal first metatarsal obliquity. These mean values are
      useful in determining if pathologic obliquity is present. In this study group,
      the mean medial obliquity angle was 3.42 degrees.

PMID- 15566705
TI  - Functional outcome (SF-36) of patients with displaced calcaneal fractures
      compared to SF-36 normative data.
AB  - BACKGROUND: The purpose of this study was to demonstrate the general health
      status after treatment of displaced intraarticular calcaneal fractures compared
      to normative data, other orthopaedic procedures, and other medical conditions.
      METHODS: Three hundred and twelve patients between 25 and 64 years of age were
      treated for displaced intraarticular calcaneal fractures at a Level I trauma
      center. Followup ranged from 2 to 8 years. The Short Form 36 Health Status Survey
      (SF-36) was used for outcome measurement. RESULTS: The scores in eight SF-36
      categories in patients with displaced intraarticular calcaneal fractures differed
      by more than five points from the population norms. This suggests that there is
      clinical and social relevance to this injury. Outcomes in patients with displaced
      intraarticular calcaneal fractures were not as good across most SF-36 categories
      as were outcomes of patients with other orthopaedic conditions. Outcomes in
      patients with intraarticular calcaneal fractures also were worse across most
      categories than outcomes in patients who had organ transplants or myocardial
      infarctions. CONCLUSION: By comparing treatment for displaced intraarticular
      calcaneal fractures with treatment for orthopaedic problems or other disease
      processes, we concluded that intraarticular calcaneal fractures are serious life
      changing events.

PMID- 15566706
TI  - Reproducibility of plantar pressure measurements in patients with chronic
      arthritis: a comparison of one-step, two-step, and three-step protocols and an
      estimate of the number of measurements required.
AB  - BACKGROUND: Plantar pressure measurement may be a helpful evaluation tool in
      patients with foot complaints. Determination of dynamic pressure distribution
      under the foot may give information regarding gait, progress of disorders, and
      the effect of treatment. However, for these measurements to have clinical
      application, reproducibility, consistency, and accuracy must be ascertained. We
      compared the reproducibility of measurements among one-step, two-step, and three
      step protocols for data collection in patients with arthritis. In addition, the
      number of measurements needed for a consistent average was determined for the
      protocol that was found to be the most reproducible. METHODS: Twenty patients
      with foot complaints secondary to arthritis participated in the study. Each
      patient was tested with a pressure platform system using two of the three testing
      protocols. Reproducibility of contact time and maximal peak pressure were
      assessed. Intraclass Correlation Coefficients (ICC) were calculated for
      measurement results among protocols. In stage two of the study, the number of
      measurements needed for a consistent average was determined by calculating the
      first three measurements, the first five measurements, and then all seven
      measurements for both feet. ICC of three, five, and seven measurements were
      compared. The two-step protocol (13 patients), which was found in stage one of
      the study to be the most reproducible, was used for this determination. RESULTS:
      Reproducibility was found to be reasonable or good for all three measurement
      protocols. The mean values of contact time for the one-step protocol were found
      to be higher than the mean values of contact time for the two-step or three-step
      protocols in both feet. The differences between the one-step and three-step
      protocols were statistically significant for the left foot only. The mean peak
      pressure did not show statistically-significant differences among the three
      protocols. The one-step and three-step protocols were not used for stage two of
      the study. Using the two-step protocol, three measurements were found to be
      sufficient for obtaining a consistent average. CONCLUSIONS: The results of our
      study indicated that the one-step, two-step, and three-step protocols of
      collecting plantar pressure measurements in patients with foot complaints
      secondary to chronic arthritis were all similar. However, the use of the two-step
      protocol is recommended over the one-step and three-step protocols; the one-step
      protocol produced a longer stance phase that did not resemble normal walking and
      when comparing the two-step and three-step protocols, the two-step protocol was
      less time consuming and less strenuous for patients with painful feet.

PMID- 15566707
TI  - Reliability of visual measurement of forefoot alignment.
AB  - BACKGROUND: The purpose of this study was to determine the interrater reliability
      of visual rating of forefoot frontal plane deformities among clinicians with
      different training. METHODS: Thirty individuals (16 men and 14 women) between the
      ages of 22 and 52 years of age participated in the study. None of the patients
      had a history of congenital deformity, pain, or trauma in the lower extremities
      during the 6 months before the study. Three clinicians of different educational
      backgrounds and experience visually evaluated each of the patients and rated
      forefoot alignment. None of the clinicians knew the rating assigned by either of
      the other two clinicians. RESULTS: The results of this study showed that two of
      the clinical raters agreed 61.7% of the time, but neither of them agreed with the
      third clinician more than 15% of the time. CONCLUSION: This study indicates that
      the commonplace method of visually rating forefoot frontal plane deformities is
      unreliable and of questionable clinical value.

PMID- 15566708
TI  - Diabetic neuropathy: review of a surgical approach to restore sensation, relieve
      pain, and prevent ulceration and amputation.
AB  - Diabetic neuropathy occurs in a stocking and glove distribution consistent with a
      systemic metabolic disease. Historically, this concept led to the conclusion that
      the only role for surgery in a patient with diabetic neuropathy is for treatment
      of wounds, amputation, or reconstruction of a Charcot foot. This article reviews
      the basic scientific and clinical research that support the concepts that
      metabolic neuropathy renders the peripheral nerve susceptible to compression in
      patients with diabetes and that decompression of lower extremity peripheral
      nerves in these patients can relieve pain, restore sensation, and prevent
      ulceration and amputation.

PMID- 15566709
TI  - Informed consent for ankle fracture surgery: patient comprehension of verbal and
      videotaped information.
AB  - BACKGROUND: The purpose of our study was to evaluate the effectiveness of using a
      videotape to give patients information about the risks, benefits, alternatives,
      and treatment of a common orthopaedic procedure before they sign consent forms.
      METHODS: During a 9-month period, 48 patients with isolated closed ankle
      fractures requiring surgical intervention were randomized into two groups that
      received either videotaped or conventional verbal information regarding consent
      for surgery. The study group watched a videotape containing information about the
      risks, benefits, and treatment alternatives, while the control group obtained
      this information verbally. To determine comprehension and retention, all patients
      completed a multiple-choice questionnaire immediately after receiving the
      information, and 37 patients (77%) were available to complete a questionnaire at
      an average of 10 weeks later. RESULTS: The videotape group outperformed the
      verbal consent group by 40.1% on the initial questionnaire (p = .0002) and by
      27.2% on the followup questionnaire (p = 0.0139). Patients with educational
      levels of less than or equal to the 12th grade performed 67.8% better on the
      initial questionnaire after watching the video than after receiving the
      information verbally. (p = .0001). CONCLUSION: Patients who received information
      about their surgery on a videotape before giving their consent demonstrated a
      significant increase in comprehension compared to patients who received this
      information verbally. The benefit was even greater for patients with lower
      education levels.

PMID- 15566710
TI  - Mycetoma of foot: a rare case report and review of the literature.

PMID- 15566712
TI  - Hepatitis E virus infection in Europe: regional situation regarding laboratory
      diagnosis and epidemiology.
AB  - Hepatitis E virus (HEV) was first identified in the excreta of an experimentally
      infected human volunteer and further confirmed by similar findings in clinical
      specimens from patients with acute jaundice disease different from hepatitis A
      and B. The HEV is a 27- to 34-nm spherical non-enveloped virus obviously
      represented by a single serotype; however, its final taxonomic definition remains
      to be established. Studies on molecular biology of this virus revealed some
      peculiar characteristics showing no homologies in its nucleotide sequence to any
      entries in the Genbank database. The HEV infection was experimentally transmitted
      to non-human primates producing a disease in many features similar to that
      occurring in humans. Recently cell lines persistently infected with the HEV have
      also been obtained. These studies provided valuable virus-specific reagents which
      were used in diagnostic tests. Currently immune electron microscopy, fluorescent
      antibody technique, latex agglutination, cDNA hybridization, and Western blotting
      are employed to prove the etiological involvement of HEV in suspected hepatitis
      cases; serological tests with synthetic substances analogous to HEV antigens are
      expected to be available soon. Reliable diagnostic procedures can be carried out
      in a number of laboratories with the locally produced reagents. The HEV infection
      is common in many hot climate countries being responsible for more than 50% of
      jaundice cases among young adults. The European region is considered to be free
      of natural foci of this infection, however, several sporadic cases of HEV disease
      were reported to occur in Europeans who developed jaundice shortly after
      returning from endemic areas. It is suspected that in the Mediterranean countries
      (Italy and Spain) the cases of HEV infection could be causatively related to the
      consumption of shell-fish cultivated in sewage-polluted waters.

PMID- 15566713
TI  - HIV-infection in Estonia.
AB  - Only a few cases of clinical AIDS have been diagnosed in the Baltic countries
      that previously were part of the Soviet Union. This suggests that the spread of
      HIV-infection has been much slower than in several other countries belonging to
      the previous Eastern Europe. To get a more precise picture of the situation, we
      have analyzed the data from seroepidemiological screening programs that have been
      conducted in Estonia since June 1987. Large population groups were tested
      according to a decree by the former soviet All-Union center on AIDS. On several
      occasions the tests were mandatory and probably had a coverage close to 100%.
      After more than a million serum samples were tested, 29 HIV-infected persons, 3
      women and 26 men have been identified. One of them was HIV-2 positive. Most of
      them live in Tallinn, the capital city of Estonia. All cases probably have a
      sexually transmitted infection. In one the infection has proceeded to clinical
      AIDS. Analysis of the gene sequences of several strains suggests that the strains
      are closely related and that the number of sources of infection is quite small.
      The study suggests that the spread of HIV in Estonia is still quite limited. A
      contributing factor may be the restricted possibilities for travel to the Western
      countries during the Soviet era.

PMID- 15566714
TI  - Seroepidemiology of hepatitis C virus in Beijing, China.
AB  - To investigate the seroprevalence of hepatitis C virus (HCV) in China we tested
      sera from healthy individuals without hepatitis and no history of parenteral
      blood exposure and from patients admitted to a hepatitis hospital in Beijing.
      Sera were tested for anti-HCV by first-generation enzyme immunoassay; selected
      positives were tested with two second-generation EIAs, one utilizing recombinant
      antigens and the other synthetic peptides. We found anti-HCV with the following
      frequencies: 10 of 164 (6%) individuals with no disease; 2 of 36 (5.5%) patients
      with acute non-A non-B hepatitis (NANBH); 26 of 39 (67%) patients with post
      transfusion NANBH; 10 of 34 (29%) patients with chronic hepatitis negative for
      hepatitis B surface antigen (HBsAg); 3 of 30 (10%) patients with chronic HBsAg
      positive hepatitis; 0 of 19 patients with acute HBsAg-positive hepatitis. Of 24
      repeat-positive sera, 19 were positive by both and 4 by one second-generation
      tests. We conclude that hepatitis C infection is common in China, that it
      contributes substantially to the incidence of post-transfusion hepatitis, and
      that HCV plays a significant role in both acute and chronic hepatitis. Further
      studies are needed to extend these observations and to define the predominant
      routes of transmission of HCV in China.

PMID- 15566715
TI  - Spin-amplified culture followed by enzyme immunoassay for detection of herpes
      simplex virus in patient specimens: a comparative study.
AB  - In a comparative study it was found that a combination technique of spin
      amplified culture and detection of herpes simplex virus (HSV) antigen in 48-h
      incubated cell culture lysate by a HSV antigen detection enzyme immunoassay kit
      (Dupont Herpchek) detected the largest number (227) of confirmed HSV positives
      when compared to standard cell culture (191) and direct Herpchek (146) on the
      same 415 clinical specimens.

PMID- 15566716
TI  - Detection of antibodies to herpes simplex virus type 2 with a mammalian cell line
      expressing glycoprotein gG-2.
AB  - The gene (US4) coding for herpes simplex virus type 2 (HSV-2) glycoprotein G (gG
      2) was cloned and constitutively expressed in Chinese hamster ovary (CHO) cells.
      The expression vector containing the dihydrofolate reductase (dhfr) gene, and the
      HSV-2 US4 gene under the control of the Simian virus 40 early promoter (SV40 EP),
      was transfected into dhfr-deficient CHO cells. The transfected cells were
      selected and amplified using methotrexate (MTX). To demonstrate that the gG-2
      produced in these transformed cells had antigenic determinants in common with the
      native glycoprotein, CHO cells expressing gG-2 were used in an immunofluorescent
      assay (IFA) for the detection of HSV-2 type-specific antibodies in human serum
      samples. Seven of eight serum samples from adults with prior episodes of culture
      proven HSV-2 infections were found to be positive by the IFA method whereas none
      of seven serum samples from young children with culture documented HSV-1
      infections were positive by IFA. Thus the recombinant CHO : gG-2 cells have
      diagnostic utility in an HSV-2 specific serologic assay.

PMID- 15566717
TI  - Evaluation of a rapid membrane enzyme immunoassay (Testpack HIV-1/HIV-2) at
      zonal, regional and district hospital laboratories in Tanzania.
AB  - The performance of a rapid and simple membrane enzyme immunoassay for antibodies
      to HIV-1 and HIV-2 (Testpack HIV-1/HIV-2) was evaluated by testing 1000 sera from
      the Kilimanjaro region of Tanzania. A sensitivity of 100% (118/118 positives) and
      specificity of 95.1% were obtained following the manufacturer's procedure. The
      specificity was significantly enhanced to 97.2% (P = 0.026) by modifying the
      Testpack procedure by including an extra was after serum adsorption to the unit
      membrane. The testing of a single specimen could be completed in 8 min and up to
      10 individual tests could be run simultaneously. There was complete agreement in
      interpretation when the results were read independently by two trained
      technicians. A built-in control insured against incorrect procedures or inactive
      reagents. In a subsequent field trial including 450 sera, one strongly reactive
      sample failed to be detected at a participating field hospital for unknown
      reasons. The Testpack reagents proved stable for up to one year at room
      temperature (25-30 degrees C). The data indicate that Testpack is suitable for
      the detection of serum antibodies to HIV and is especially applicable in
      laboratories with limited facilities. When used to test African sera which are
      known to produce a high degree of false positivity, an extra wash of the membrane
      after serum adsorption is recommended.

PMID- 15566718
TI  - Correlation of quantitative human cytomegalovirus pp65-, p72- and p150
      antigenemia, viremia and circulating endothelial giant cells with clinical
      symptoms and antiviral treatment in immunocompromised patients.
AB  - Human cytomegalovirus (HCMV) replication in peripheral blood polymorphonuclear
      (PMNL) and mononuclear (MNL) leukocytes was investigated by quantitative
      determination of pp65-, p72- and p150-antigenemia and viremia in 7 (4 heart or
      heart-lung transplanted and 3 AIDS) immunosuppressed patients. These parameters
      were correlated with appearance of clinical symptoms and with their disappearance
      following antiviral treatment. Onset and progression of HCMV infection was
      associated to increasing levels of pp65-, p72- and p150-antigenemia and viremia,
      and a significant correlation was found between antigenemia and viremia in both
      PMNL and MNL. pp65-antigenemia showed absolute levels higher than p72- and p150
      antigenemia both in PMNL and MNL, but PMNL showed figures consistently higher
      than MNL for all 3 viral proteins. levels of p150-antigenemia and viremia > 100
      were associated to clinical symptoms in patients with peak of infection within 40
      days after transplantation. In addition, number of HCMV-infected circulating
      giant cells (CGC) progressively increased in the presence of an organ syndrome.
      Antiviral treatment with either foscarnet or ganciclovir induced rapid
      disappearance of p150-positive PMNL and MNL as well as CGC, followed by
      disappearance of p72-positive leukocytes within a few days. pp65-positive cells
      were the last to disappear. Reported data suggest that viral replication may
      occur not only in MNL, but also in PMNL. Interaction between HCMV-infected
      circulating leukocytes and CGC may represent one of the major pathogenetic
      pathways for the development and dissemination of HCMV infection in
      immunocompromised patients.

PMID- 15566719
TI  - Prenatal treatment of congenital human cytomegalovirus infection by fetal
      intravascular administration of ganciclovir.
AB  - Ganciclovir was administered 'in utero' for 12 days in a 29-week-old fetus with
      ascertained congenital human cytomegalovirus (HCMV) infection, thrombocytopenia
      and elevated gamma-glutamyl transferase (gammaGT) value. Efficacy of therapy was
      shown by reduction in virus titer of amniotic fluid and fetal urine,
      disappearance of viral DNA in fetal blood, and normalization of platelet count
      and gammaGT value. However, stillbirth occurred at 32 weeks of gestation and HCMV
      inclusion bodies were detected in kidneys, lungs, heart and pancreas at autopsy.
      During therapy, side-effects,possibly related to ganciclovir administration, were
      observed.

PMID- 15566721
TI  - Human herpes virus-6 (HHV-6) in diseases.

PMID- 15566722
TI  - Deficiency in interferon production by leukocytes from children with recurrent
      respiratory infections.
AB  - In vitro interferon production by peripheral blood mononuclear cells from 50
      children suffering from recurrent upper respiratory tract infections was
      examined, and compared with that of 50 healthy children. Five respiratory
      pathogenic viruses and Mycoplasma pneumoniae were used as inducers. Cells from
      every child responded to at least three out of the six inducers by interferon
      production. As a group, cultures prepared from patient cells showed decreased
      production of IFN when stimulated with adeno, rhino, corona or RS viruses or with
      the mycoplasma. Similar trend between the two groups of children was seen as
      regards influenza A virus induced IFN production in leukocyte cultures. These
      results corroborate our previous findings that relative deficiency in interferon
      production appears to be inducer-specific, and suggest that this phenomenon may
      have a role in the pathogenesis of recurrent respiratory infections.

PMID- 15566723
TI  - Isolation of St. Louis encephalitis virus from a killer whale.
AB  - We report the isolation of St. Louis Encephalitis (SLE) virus from a mature male
      killer whale (Orcinus orca). This represents the first isolation of SLE virus
      from a marine mammal. The animal presented with reduced appetite, rapidly became
      lethargic and subsequently died. Virus-induced CPE was observed in a dolphin cell
      line, SP-1K (ATCC CCL 78), inoculated with brain, kidney, and lung tissues
      obtained at necropsy. Electron microscopy of infected SP-1K cells revealed the
      presence of virions having morphology and size resembling members of the
      Flaviviridae. Final identification as SLE virus was made by neutralization and
      immunofluorescence staining tests.

PMID- 15566724
TI  - Evaluation of five hepatitis C virus screening tests and two supplemental assays:
      performance when testing sera from sexually transmitted diseases clinic attendees
      in the USA.
AB  - The performances of five screening tests (recombinant peptide-based first and
      second generation tests from Abbott and Ortho, and a synthetic peptide-based test
      from Biochem Immunosystems) and two supplemental tests: recombinant peptide-
      based, Abbott neutralization test and Chiron second generation recombinant
      immunoblot assay (RIBA 2), were evaluated for their ability to detect hepatitis C
      virus (HCV) antibodies in a population of 276 individuals attending a sexually
      transmitted diseases (STD) clinic in the USA. Although the five screening tests
      produced a variable number (35-62) of repeatedly reactive samples, only 13%
      (36/276) were classified as true positives by the supplemental tests. Thirty-four
      of the 36 were reactive by all screening tests and 32 of the true positives were
      reactive by both supplemental tests, while 2 did not neutralize but were reactive
      in the RIBA 2 test. Of the remaining 2 of the true positives which were
      discordant by several of the screening assays, 1 was confirmed by both
      supplemental assays but the other required a chemiluminescent enhancement
      technique to show positivity in RIBA 2. The sensitivities of the first and second
      generation Abbott and Ortho tests ranged from 97% to 100% and that of the Biochem
      test was 94%. The specificities of these tests ranged from 89.2% to 99.6%. The
      second generation Ortho test presented 9.4% (26/276) false positives. The use of
      second generation Ortho as a screening test would lead to an excessive number of
      confirmatory false positives. the positive predictive values of the screening
      tests ranged from 58.1% to 97.1%. Although the synthetic peptide based Biochem
      test exhibited the best overall indices, the presence of 2 false negative results
      would prevent its use as a singular screening test. Nevertheless its high
      specificity may lend itself to be used as a second screening test before
      confirmatory testing with RIBA 2.

PMID- 15566725
TI  - Detection of influenza A in clinical specimens and cell culture fluid by a
      commercial EIA.
AB  - A MoAb-based capture EIA for the direct detection of influenza A from clinical
      samples was compared with cell culture isolation. A total of 330 respiratory
      specimens were submitted for detection of influenza A and/or other respiratory
      viruses. Influenza A was detected in 39 of 330 (12%) respiratory samples by
      culture or EIA. There were 33 concordant (EIA+/Culture-) samples (82%), and 6
      discordant samples (3 EIA +/Culture-; 3 EIA-/Culture+). Compared to viral
      isolation, the EIA had a sensitivity of 92%, a specificity of 98%, with positive
      and negative predictive values of 92% and 99%, respectively.

PMID- 15566726
TI  - Immunogenicity and adverse reactions of influenza vaccination in elderly patients
      given acetaminophen or placebo.
AB  - The objective was to examine the antibody responses to influenza immunization in
      an elderly population and the effect of prophylactic acetaminophen on adverse
      responses due to inactivated whole virus vaccine containing influenza A (H3N2 and
      H1N1) and B antigens. During the autumn of 1990, 100 patients 65 years or older
      were immunized and randomly allocated to receive placebo or 1,950 mg (2 x 975 mg)
      of acetaminophen. They recorded any local and systemic side effects over a 3-day
      period. Serology was performed on pre- and post (4-6 weeks) -vaccination sera.
      Age and gender distribution in the study were: 47% who were 75 years or older,
      and 61% of the patients were female. Most of the patients (97%) had pre-existing
      antibodies to Influenza A or B. Average peak preimmunization antibody titers were
      40 to B Yamagata and A Taiwan (H1N1) and 80 for A Shanghai (H3N2). Half of each
      treatment group had a 4-fold or greater rise in antibody titer in response to the
      vaccine. Only 30% of patients immunized the previous year but 80% of those never
      vaccinated previously demonstrated a 4-fold or greater serological response to
      the vaccine. However, measurement of protection rates (HI >/= 40) before and
      after vaccination indicated 81.1-100% protection for the 3 viruses not influenced
      by treatment, gender or a history of previous vaccination. Both treatment groups
      had equally small numbers of patients who recorded systemic symptoms of
      drowsiness, myalgia, fever and chills and about 50% had arm soreness. Although
      about 80% of previously unimmunized adults mounted a 4-fold antibody rise to
      influenza vaccine antigens whereas booster effects were seen in only 30% of those
      immunized the previous year, protection rates were high (81-100%) after
      immunization and were not affected by acetaminophen treatment. Adverse effects
      (15% systemic and 50% local) were not ameliorated by 1950 mg of acetaminophen in
      these elderly patients.

PMID- 15566727
TI  - Comparison of enterovirus 71 (E71) isolated from a patient with hand-foot-and
      mouth disease in China to prototype E71 BrCr strain by polymerase chain reaction
      using a unique primer pair.

PMID- 15566728
TI  - Diagnosis of infection with human T-lymphotropic virus type II (HTLV-II) in
      Norwegian HIV-infected individuals.
AB  - Sera from 298 HIV-infected individuals from Southern Norway were examined for
      antibodies against HTLV. 30 sera (10.1%) were HTLV-II positive and 1(0.3%) HTLV-I
      positive. 25 of the HTLV-II infected subjects were intravenous drug abusers
      (IVDAs), giving a prevalence of HTLV-II infection of 24.5% in this group.
      Examination of blood samples by polymerase chain reaction followed by restriction
      enzyme analysis or sequencing confirmed the serological diagnosis. To evaluate
      current screening and verification HTLV tests, 44 sera were examined using a
      gelatin particle agglutination test, 5 different enzyme-linked immunoassays
      (ELISA) and 4 Western blots (WB). While earlier ELISAs and WBs were inadequate, a
      recent ELISA and WB including recombinant envelope glycoproteins from both
      viruses permitted serological diagnosis and distinction between HTLV-I and HTLV
      II. Thus, HTLV-II now spreads among IVDAs in a North-European country. Health
      authorities in other countries should estimate the magnitude of the problem to
      decide upon measures to avoid transmission through blood transfusion.

PMID- 15566729
TI  - Evaluation of serum antibody response to a newly identified B-cell epitope in the
      minor nucleocapsid protein L2 of human papillomavirus type 16.
AB  - The aim of this work was to identify B-cell epitopes in the minor nucleocapsid
      (L2) protein of human papillomavirus (HPV) type 16 and characterization of allied
      antibody response. Serum samples of 513 individuals (323 women with various
      degrees of cervical atypia, 150 men and 40 small children) were available for the
      study. Synthetic peptides overlapping the L2 protein of HPV 16 twice were applied
      in ELISA for epitope scanning and antibody determination. An HPV 16 L2 derived
      dodecamer SGYIPANTTIPF (amino acids 391-402) proved to be the major B-cell
      epitope. Both IgA antipeptide antibody positivity (range 7-28%) and mean IgA
      antibody levels (range 13.2 EIU to 42.4 EIU, P < 0.05) increased with the degree
      of cervical atypia, whereas antipeptide IgG antibodies showed an opposite trend.
      During a 2-years follow-up significantly (P < 0.0005) decreasing IgA antibody
      levels to the SGYIPANTTIPF peptide were associated with regression of
      koilocytotic atypia. Analysis of anti-peptide IgA antibodies of 118 women with
      known HPV type revealed that a majority of positives had HPV 16/18 DNA. It was
      concluded that antibody response to the newly discovered peptide was partially
      type- and disease-specific. Our results also suggest an impairment of the IgG but
      not IgA class antibody response to HPV 16 in patients with persistent cervical
      HPV infection.

PMID- 15566730
TI  - Are seroepidemiological surveys for human immunodeficiency virus infection based
      on tests on pools of serum specimens accurate and cost-effective?
AB  - Serum specimens (n = 17668) from UK antenatal patients in the Thames Regions were
      tested by Wellcozyme HIV 1/2 EIA singly and in pools of 6, 12 and 24: 35 (0.2%, 1
      in 505) were confirmed as anti-HIV positive. The pools of 12 were also tested for
      anti-HIV 1/2 by IAF Biochem, Behring and Diagnostics Pasteur EIAs. All 35
      positive specimens were easily detectable after pooling in groups of 12. The
      false positive rate for Wellcozyme was nearly halved compared with individual
      testing (1 in 309 false positive compared with 1 in 174). For the other assays
      false positive rates on pools of 12 were: IAF Biochem 1 in 193, Behring 1 in 140,
      Diagnostics Pasteur 1 in 1547. Twenty-two known anti-HIV 2-positive sera were
      detected by all four EIAs when diluted as in pools of 6 and 12, but by only three
      EIAs in pools of 24 and 48. Pooling in groups of 6 did not seem to delay
      detection of HIV 1 seroconversion, but pooling in groups of 12, 24 and 48 might
      delay it by 1, 2 and 3 weeks respectively. For this study the effect of pooling
      in groups of 12 would have been a reagent saving of 87-91% and a labour saving of
      about 50%. Because of the low HIV incidence and rarity of specimens collected
      around seroconversion in UK, little, if any, loss of sensitivity would result
      from it. Pooling in groups of 12 has therefore been chosen for the screening of
      anonymous antenatal specimens in the UK.

PMID- 15566731
TI  - Antiviral susceptibility testing of cytomegalovirus: criteria for detecting
      resistance to antivirals.
AB  - Testing cytomegaloviruses for antiviral susceptibility is increasing especially
      since the reports of 'resistance' to ganciclovir and foscarnet (Erice et al.,
      1989; Knox et al., 1991). There is however no standardized method for
      susceptibility testing nor are there criteria for designating an isolate as
      sensitive or resistant. In a previous paper we utilized a plaque reduction assay
      and suggested that a resistant strain be defined as one requiring > 12 microM
      ganciclovir for inhibition of 50% of viral plaques. (Drew et al., 1991) This
      concentration was chosen because it was at least four-fold greater than the mean
      concentration required to inhibit pretherapy isolates. In this paper we present
      the results of testing a large number of isolates prior to and during therapy
      with either ganciclovir or foscarnet. By analyzing the results of these assays we
      propose revised criteria for susceptibility of cytomegalovirus </= 5 microM for
      ganciclovir and <400 microM for foscarnet.

PMID- 15566732
TI  - Southern blot and dot blot hybridisation compared to PCR for the detection of
      human papillomavirus DNA in biopsies of the uterine cervix from women with
      dysplasia.
AB  - The aim of this study was to compare the sensitivity of Southern blot (SB) and
      dot blot (DB) hybridisation with polymerase chain reaction (PCR) for the
      detection of HPV in cervical biopsies from samples with differing histology. One
      hundred and forty seven women with cervical dysplasia had biopsies performed; one
      sample was analyzed for HPV DNA from types 6/11, 16, and 18 by SB, DB and PCR (L1
      consensus primer and type specific probes) while an adjacent sample was examined
      histologically. The histology of the samples was normal in 40 (27%), squamous
      metaplasia in 25 (17%), inflammation 2 (1%) HPV infection 24 (17%), cervical
      intraepithelial neoplasia (CIN) grade I in 11 (7%), CIN II in 18 (12%), CIN III
      in 22 (15%), while 5 (3%) had invasive cancer. The number of biopsies positive
      for HPV DNA from types 6/11, 16, and 18, using the different hybridisation
      methods was 56 (38%) by dot blot, 57 (39%) by Southern blot hybridisation and 66
      (45%) by PCR. When the L1 consensus primer was used 100 (68%) specimens were
      positive by PCR. The sensitivity of SB and DB hybridisation, as compared with PCR
      (type specific probes 6/11, 16, 18) was greater in biopsies with abnormal
      histology (histological grades of HPV infection and greater, as a group)
      (sensitivity of SB 83%, DB 74%) than those with normal and metaplastic change (as
      a group) (sensitivity of SB 44%, DB 35%) (P < 0.005 for SB and DB) (inflammation
      excluded from analysis). This study demonstrated that the sensitivity of SB and
      DB hybridisation, relative to PCR is greater in samples with abnormal histology
      than in samples with normal histology.

PMID- 15566733
TI  - A novel approach to diagnosis of acute HCV infection in an immunosuppressed
      transplant recipient.

PMID- 15566734
TI  - Detection of antibodies to HIV in homologous sets of plasma, urine and oral
      mucosal transudate samples using rapid assays in Tanzania.
AB  - The aim of this study was to evaluate the performance of commercially available
      anti-HIV assays when testing plasma, urine and oral mucosal transudate (OMT)
      samples for the presence of antibodies to HIV. Homologous sets of plasma, urine
      and oral mucosal transudate specimens were collected from 288 hospitalized
      patients in northern Tanzania and tested for antibodies to HIV using a routine
      enzyme immunoassay (Recombinant 3rd Generation EIA, Abbott) and two rapid assays
      (Testpack HIV-1/HIV-2; Abbott and SUDS HIV-1, Murex). Incubation times and/or
      sample volumes when testing OMT or urine were increased as compared to those
      recommended for plasma. The corresponding plasma specimens from all repeatedly
      reactive samples and samples presenting discordant results were subjected to
      confirmational testing by an HIV-1/2 Western blot. A total of 15.3% (44/288) of
      the plasma samples were anti-HIV-1 positive by Western blot. The sensitivity
      using plasma was 100% by all assays, 69.7-97.7% using urine, and 92.7-100% using
      oral transudate specimens. The sensitivity of both rapid assays was excellent and
      higher than the EIA when testing OMT. Specificities ranged from 98.8-100% for
      plasma, 99-100% for urine and were 100% by all assays using oral samples. The
      results obtained using oral mucosal transudate specimens and rapid assays were at
      least comparable to those obtained with plasma, while the use of urine specimens
      produced suboptimal sensitivities with two of the three assays. The testing of
      alternative body fluids for antibodies to HIV is yet another strategy that may be
      applicable, particularly in developing countries.

PMID- 15566735
TI  - Comparison of four enzyme immunoassays for the detection of cytomegalovirus IgG
      antibodies.
AB  - Four commercial enzyme immunoassays (EIA), namely the Behring Enzygnost EIA (BE
      EIA), Abbott IMx, Whittaker CMV STAT Test Kit and Diamedix assay, were evaluated
      for the detection of CMV IgG. The methods were compared as to sensitivity,
      specificity, positive and negative predictive values, global agreement, ease of
      performance and, for a small number of specimens, reproducibility. Discordant
      results were resolved by using the Gull CMV indirect fluorescent antibody (IFA)
      method. Our data suggest that all four assays were valuable screening tools for
      the detection of CMV IgG based on their high sensitivity and high negative
      predictive value. However, differences were noted in the reproducibility level
      and in the incidence of false-positive, equivocal and nonspecific results
      regarding certain tests in particular. In our hands, the Abbott IMx and the BE
      EIA ranked high in the performance characteristics for a good screening test, yet
      the Abbott IMx offers the added advantages of being the easiest to perform and
      having the most rapid turnaround time.

PMID- 15566736
TI  - Anti-HIV testing by automated systems.
AB  - The accuracy and ease of use of three automated test systems (Behring Opus,
      Boehringer Mannheim ES300 and bioMerieux Vidas) and their associated assays (Opus
      HIV 1 + 2, Enzymun-Test Anti-HIV 1 + 2 and Vidas HIV 1 + 2) for the detection of
      anti HIV-1 and anti HIV-2 in human serum and plasma were investigated by testing
      them against a panel of 364 well-characterised specimens. The panel included
      specimens confirmed to contain anti HIV-1 (n = 65) and anti HIV-2 (n = 25),
      specimens collected during HIV-1 seroconversion (n = 40), specimens (n = 116)
      which had given spurious reactions in a variety of anti-HIV screening assays,
      specimens from patients infected with anti HTLV-I (n = 18) and specimens from
      unselected blood donors (n = 100). Excluding the seroconversion specimens, all
      three assays were 100% sensitive. Observed specificities ranged from 98.3% to
      99.6%. For the seroconversion specimens the Vidas HIV 1 + 2 was the most
      sensitive overall. All three assays were as sensitive and specific as most of the
      conventional anti-HIV enzyme immunoassays currently available. The Opus and Vidas
      systems would be convenient for clinical laboratories handling small to medium
      numbers of specimens per day. The Boehringer Mannheim ES300 is designed for
      larger scale use and required more familiarisation.

PMID- 15566737
TI  - A ribonuclease protection assay for the direct detection and quantitation of
      hepatitis C virus RNA.
AB  - A ribonuclease protection assay (RPA) was developed for the direct detection and
      quantitation of HCV RNA in infected patients' sera or plasma using HCV [(32)P]RNA
      from the conserved 5'-untranslated region (5'-UTR) as a probe. We were able to
      directly detect the presence of HCV RNA by RPA in several infected patients'
      samples. The viremic status of HCV infected patients with indeterminate
      recombinant immunoblot assay (RIBA II) was also determined by this assay.
      Polymerase chain reaction (PCR) was also performed on all these samples and were
      found to be positive with a concordance of 100% between the results of PCR and
      RPA. The RPA was able to detect approximately 1 pg of HCV RNA. A limited sequence
      heterogeneity among HCV isolates was also observed by this assay, suggesting that
      this may be a faster method of detecting heterogeneous HCV sequences in patients'
      samples. This simple and specific method could be used to quantitate HCV RNA in
      order to better determine viremia and follow the course of HCV infection
      especially when RIBA II results are indeterminate.

PMID- 15566738
TI  - Phase I/II trial of didanosine (2',3'-dideoxyinosine) in hemophiliac patients
      with AIDS or AIDS-related complex.
AB  - Forty-three hemophiliacs with AIDS or ARC received a daily dose of 334 or 500 mg
      didanosine (2',3'-dideoxyinosine or ddI) orally in 2 divided doses in phase I/II,
      open-label clinical trial conducted in Japan. Twenty-eight patients completed 6
      months of therapy. There was an increase in circulating CD4(+) cells in 19
      valuable patients from 91 +/- 25 (mean +/- SE) at entry to 131 +/- 38 at 24 weeks
      of therapy P = 0.01; Wilcoxon signed rank). Fourteen of 37 patients met the
      criteria for CD4 rise >/= 50/mm3 rise or >/= 50% increase from entry values) for
      more than 4 consecutive weeks. Twenty patients were p24 positive at entry. Nine
      out of the 10 evaluable patients (90%) showed a decline in p24 antigen at weeks
      20-24 (P = 0.02). Thirty-five patients had symptoms related to HIV-1 infection at
      entry. Twenty-seven patients reported improvements in constitutional symptoms
      during therapy. Nine patients presented with possible drug-related adverse
      effects, and didanosine was discontinued in 6 patients (one each with edema;
      abdominal pain with anorexia; hematuria with edema and rash; sense of abdominal
      distension with anorexia; diarrhea and abdominal pain; and irritability). One
      patient had a transient increase in serum amylase level to twice the upper limit
      of normal, but he continued to receive the drug. These data suggest that
      didanosine was generally well tolerated in hemophiliacs with AIDS or ARC, and its
      administration correlated with improvement in constitutional symptoms and
      laboratory findings. The adverse effects of didanosine seen in this population
      were moderate to mild, and no complications related to hemorrhagic diathesis were
      observed, although the relative risk of acute pancreatitis in this population
      (while not seen in the present study to date) requires more study.

PMID- 15566739
TI  - Avoiding false positive HIV results on life assurance proposers: the necessity
      for follow-up.
AB  - The serological reaction to HIV infection is almost invariably a dynamic
      progression towards strong reactivity to a wide range of viral antigens.
      Serological diagnosis should therefore be based either on the presence of this
      wide range in a single specimen or on the demonstration of increasing activity
      between two specimens collected at an interval of two or more weeks and tested in
      parallel. When a specimen is reactive a second should in any case be collected to
      check the identity of the first. These precepts are sometimes being ignored,
      especially in non-clinical testing, e.g., for purpose of life assurance. Two
      recent cases in which there were false but unchanging enzyme immunoassay and
      Western blot reactions that might have been interpreted as positive illustrate
      the potential for error.

PMID- 15566740
TI  - HHV-6 infection in Italy: characterization of an endemic isolate and
      seroepidemiologic analysis.
AB  - A biologic, immunologic and molecular characterization of an HHV-6 isolate (BA92)
      rescued by the peripheral blood mononuclear cells of a child affected by Exanthem
      subitum is reported. The comparison with the known HHV-6 prototype strains showed
      that BA92 is indistinguishable from the Z29 isolate, and can be included in the
      variant B group of HHV-6. A seroepidemiologic analysis of the antibody response
      to BA92 of normal individuals as well as patients affected by diseases
      potentially associated to HHV-6 infection has shown an overall seroprevalence of
      81%, and that no variations in seroprevalence or in antibody geometric mean titer
      are observed assaying the sera also against G.S., U1102, or Z29 infected cells,
      respectively. These findings indicate: (1) HHV-6 infection is widely diffuse in
      Italy; (2) it is not possible to discriminate between the viral variants by the
      currently available IF assays, and (3) no conclusions can be drawn on the
      potential association of HHV-6 with any of the diseases examined.

PMID- 15566741
TI  - Early kinetics of antibody response to inactivated influenza vaccine.
AB  - The aim was to examine the rapidity of haemagglutination inhibiting (HI) antibody
      response induced by immunization with a current inactivated trivalent influenza
      vaccine. Five to six sequential serum samples collected in autumn 1992 from each
      of 68 vaccinees in three age groups were studied for HI antibodies to ten
      influenza virus strains representing vaccine and epidemic viruses. Geometric mean
      titres, response rates and protection rates are presented. Response rates of >
      70% were overall, but not until two weeks after the vaccination. Significant two-
      and four-day post-vaccination antibody responses were detected only occasionally.
      In previously vaccinated persons, average antibody titres to some of the viruses
      decreased during the first days after the vaccination. In the subsequent samples,
      the titres remained lower than in persons who were not vaccinated against
      influenza in preceding years. Protection against influenza infection may be
      frequently developed not until two weeks after vaccination. This has relevance to
      prophylactic administration of amantadine and rimantadine when an influenza A
      outbreak is imminent and the vaccination is late.

PMID- 15566742
TI  - Influence of HIV-infection on the phagocytic activity of monocytes/macrophages
      and granulocytes.
AB  - Because of the great importance of phagocytosis as a key process in host defence,
      the influence of HIV-infection on the phagocytic activity of
      monocytes/macrophages (M0/MAC) and granulocytes was investigated. Therefore,
      blood samples from the peripheral blood of 70 HIV-infected individuals were
      incubated with fluorescein isothiocyanate (FITC) labeled Escherichia coli. The
      uptake of the bacteria was monitored by flow cytometer analysis. A strong and
      significant increase in the relative number of phagocytic granulocytes was
      observed ranging from 12.8% in an uninfected control collective to over 30% in
      AIDS patients. This effect was obtained for all patients and independent of the
      stage of disease. For monocytes, only marginal changes were found in their
      phagocytic function. These data suggest that the high susceptibility of HIV
      patients for secondary infections is not linked to a loss of phagocytic ability
      of monocytes/macrophages and/or granulocytes.

PMID- 15566743
TI  - Detection of hepatitis C virus RNA by reverse-transcriptase and polymerase chain
      reaction: clinical applications of quantitative analysis.
AB  - Polymerase chain reaction (PCR) applications to diagnostics allowed the detection
      of viral nucleic acids in expected and unexpected clinical circumstances. This
      has raised some scepticism on the practical usefulness of PCR in the routine
      laboratory and emphasized the need for quantitative analysis. We addressed this
      question detecting HCV-RNA by a single step RT-PCR in serum samples from 50
      patients with chronic non-A, non-B hepatitis included in clinical trials for
      recombinant alpha-interferon therapy. We obtained at least 5 serum specimens from
      each patient (baseline, during and after therapy samples) during an 18-month mean
      follow-up (range 12-45 months). RT-PCR was performed on total RNA extracted from
      100 microl serum aliquots using primers for the highly conserved 5'NCR of HCV-RNA
      and 35 amplification cycles. PCR products were analyzed by agarose gel
      electrophoresis and Southern blot hybridization against a P(32)-oligonucleotide
      probe. Sensitivity was evaluated in separate experiments on tenfold dilutions of
      a reference Chimp serum containing 10(6) CID(50)/ml. The overall sensitivity of
      our assay ranged between 10(2) and 10(3) genome Eq./ml. We establish a
      semiquantitative score system to evaluate viremia levels: 2 = HCV-RNA levels
      >10(4) genome Eq./ml; 1 = levels between 10(3) and 10(4) g.Eq./ml; 0 = levels
      less than 10(2) g.Eq/ml. The reproducibility of this scoring system was confirmed
      testing repeatedly in duplicate end-point dilutions of positive serum samples. A
      statistically significant relation was observed between elevated HCV-RNA and ALT
      values (83.8%, chi-square 159.963 P < 0.001). Response to IFN therapy was
      significantly better in patients with lower baseline HCV-RNA levels. A time
      relation was found between flare-ups of serum HCV-RNA levels and ALT elevations
      higher than 3 x normal values viremia elevations coincident or occurring about 1
      month earlier than ALT elevations. This finding suggests that immuno pathogenesis
      might be responsible of HCV-induced liver damage as in chronic hepatitis B where
      identical relations were observed between viremia and ALT serum levels. In
      conclusion, single-step HCV-RNA RT-PCR can be a specific and reproducible
      semiquantitative assay and provides useful diagnostic informations for
      therapeutic decision making and monitoring of HCV-infected patients.

PMID- 15566744
TI  - Detection of anti-HIV in saliva and urine at the time of seroconversion.
AB  - To determine whether there is a delay between the appearance of anti-HIV in
      serum/plasma and its detection in saliva and urine, salivary and urine specimens
      were collected from nine individuals who, on the basis of increasing IgG anti-HIV
      reactivity, Western blot band patterns and presence of strong IgM anti-HIV
      reactivity in their serum specimens, were believed to have recently become anti
      HIV-positive. Serum from 8 of these patients and 3 commercial panels of plasma
      specimens collected during seroconversion were diluted to mimic the low
      immunoglobulin concentrations present in saliva and urine and tested in
      Wellcozyme HIV 1 + 2 GACELISA and four commercial EIAs intended for testing serum
      specimens. The 9 pairs of saliva and urine specimens were collected between 4 and
      43 days (median 24 days) after the first evidence of seroconversion. All were
      reactive by Wellcozyme HIV 1 + 2 GACELISA and gave optical density/cut off
      (OD/CO) ratios in the range 3.8 to 9.8 (median 5.2) for dribbled saliva and 2.4
      to 10.1 (median 6.3) for urine. Salivary specimens taken with commercial
      collection devices gave OD/CO ratios in the range 1.6 to 10.6 (median 5.9). In
      the serum/plasma specimens Wellcozyme HIV 1 + 2 GACELISA detected anti-HIV at
      higher dilutions than the other assays, often with a 100-fold or more difference.
      Saliva and urine specimens were all strongly reactive by Wellcozyme HIV 1 + 2
      GACELISA. We therefore predict that it would first detect anti-HIV in salivary
      and urine specimens at about the same time as it becomes detectable in
      serum/plasma but that other commercial EIAs would not.

PMID- 15566745
TI  - A conformational epitope on the dimer of the fusion protein of respiratory
      syncytial virus detected in natural infections.
AB  - A murine monoclonal antibody (MAb), 2D8, was used in immunofluorescence reactions
      to detect respiratory syncytial virus (RSV) antigen in clinical specimens.
      Nasopharyngeal epithelial cells from 63 of 66 children with RSV infections
      reacted with this MAb. The MAb was further characterized and was demonstrated to
      recognize a conformational epitope on the dimer of the fusion protein of RSV. No
      reaction was detected with the MAb, 2D8, on Western blots of antigen prepared
      from RSV-infected HEp-2 cells under reducing conditions. Under non-reducing
      conditions, 2D8 reacted with a 145-170 K protein; this reactivity was lost when
      the antigen preparation was heated to 100 degrees C. 2D8 reacted with purified F
      glycoprotein of RSV Long in an ELISA, neutralized infectivity of RSV by >50% at a
      dilution of 1:500, and was able to inhibit cell-to-cell fusion of RSV-infected
      cells. In a competitive ELISA, the epitope detected by 2D8 was localized to
      antigenic site A. The conformational epitope detected by 2D8 required protein
      dimerization and glycosylation for full reactivity. This report extends previous
      characterizations of the F protein in its native state in that the MAb defines a
      conformational epitope on the fusion protein dimer that is expressed in natural
      infections and elicits antibody that can neutralize virus infectivity and inhibit
      cell-to-cell fusion. In addition to its application as a diagnostic reagent, this
      MAb can be of use in testing preparations of RSV or purified F protein in which
      the purification or extraction processes could have destroyed conformational
      epitopes.

PMID- 15566746
TI  - Detection and identification of human papillomavirus DNA in genital tract by
      digoxigenin labelling using the polymerase chain reaction method.
AB  - We propose here a simple and rapid method of Human Papillomavirus (HPV) detection
      applied to genital samples. The method consists of a polymerase chain reaction
      (PCR) of samples using a consensus primer ser (Snijders et al., 1990) with
      labelling by Dig-dUTP (Digoxigenin deoxyuridine triphosphate) during
      amplification. Type identification was carried out by hybridization of the
      labelling PCR product with a panel of different plasmidic HPVs dotted beforehand
      on nylon membranes. Forty-five genital samples were tested with this method (30
      samples with evident signs of HPV infection, and 15 cervical scrapes which had a
      normal colposcopic examination and no cytologic signs of HPV infection). We found
      good sensitivity and specificity levels. The labelling method during PCR did not
      modify the sensitivity of PCR. Forty-five genital samples were analyzed by this
      technique and compared with the results of dot-blot and two PCR methods using
      different primers. They showed a good correlation except in four samples (high
      grade cervical lesions) which seemed to show a partial deletion or rearrangement.
      Our method, used for the first time in HPV detection, needed just one PCR and one
      dot-blot, thus saving an important amount of time and also decreasing examination
      costs.

PMID- 15566747
TI  - A shortened dengue IgM capture ELISA using simultaneous incubation of antigen and
      peroxidase-labeled monoclonal antibody.
AB  - A shortened IgM capture ELISA for the detection of dengue IgM antibodies using
      simultaneous incubation of antigen and peroxidase-labeled monoclonal antibody was
      described. The shortened two-step assay was compared with the four-step IgM
      capture ELISA on sera from dengue patients confirmed by the hemagglutination
      inhibition (HI) test. When paired acute and convalescent sera were tested, the
      shortened ELISA showed 100% agreement with HI results. It detected dengue IgM
      antibodies in the acute sera of 66% of patients with a primary dengue infection,
      60% of patients with a secondary infection, and 98% of patients with a
      presumptive secondary infection. When the results of 151 dengue patients were
      combined, 75% of the acute sera were positive by the shortened IgM capture ELISA.

PMID- 15566748
TI  - Evaluation of the WHO human immunodeficiency virus (HIV) antibody testing
      strategy for the diagnosis of HIV infection.
AB  - OBJECTIVE: To evaluate a WHO testing strategy based on the use of two consecutive
      enzyme-linked immunosorbent assays (ELISA) as an alternative to ELISA followed by
      Western blotting (WB) for the serologic diagnosis of HIV infection. STUDY DESIGN:
      The study was of 2069 consecutive serum specimens from patients suspected of HIV
      infection received for HIV diagnostic testing at the HIV laboratory, Muhimbili
      Medical Centre, Dar es Salaam. The strategy involved testing all sera with
      Behring indirect anti-HIV 1 + 2 peptide ELISA, followed by Wellcozyme anti-HIV-1
      recombinant competitive ELISA on those sera reactive by the first ELISA. WB was
      done on a sample of the sera reactive on both ELISAs and on all those giving
      discordant results on the two ELISAs. Of the 2069 sera tested, 837 (40.5%) were
      negative on the first ELISA, 1172 (56.6%) were reactive on both ELISAs and 60
      (2.9%) were initially reactive on the first test but not on the second assay.
      RESULTS: Of the 1172 sera reactive on both ELISAs, 329 (28.1%) were tested by WB.
      The diagnostic accuracy of the WHO alternative testing strategy using WB
      confirmation as the 'gold' standard was as follows: sensitivity 99.4% (326/328),
      specificity 99.7%, (893/896), positive predictive value 99.1% (328/331) and
      negative predictive value 99.8% (893/895). Repeated testing by ELISA of the sera
      which initially gave discordant results on the two ELISAs increased the
      sensitivity to 100%. Three sera giving false positive reactions on both ELISAs
      became negative on both ELISAs after retesting. In order to achieve a specificity
      and a positive predictive value of 100%, it would have been necessary to subject
      all sera reacting on both ELISAs to retesting on one ELISA. CONCLUSIONS: A second
      ELISA based on different antigens and a different test principle compared with
      the first ELISA could be used as an alternative to the WB assay for confirmation
      of HIV antibodies. However, some modifications of the WHO strategy for diagnostic
      HIV antibody testing were required in order to maximize the diagnostic accuracy.

PMID- 15566749
TI  - Hepatitis C virus serological and polymerase chain reactions in human
      immunodeficiency virus-positive and -negative patients.
AB  - BACKGROUND: Polytransfused patients may be dually infected with hepatitis C virus
      (HCV) and human immunodeficiency virus (HIV). OBJECTIVES: To assess the
      correlation of antibodies to HCV with viral RNA in serum as determined by
      polymerase chain reaction (PCR) in anti HIV-positive and -negative haemophiliacs.
      STUDY DESIGN: Serum from 150 Patients with or without HIV infection were examined
      for anti-HCV by second generation enzyme-linked immunosorbent assay (ELISA) and
      recombinant immunoblotting assay (RIBA). A sample was also tested in a nested
      reverse transcription PCR for a conserved sequence of the 5' untranslated region
      of HCV. PCR-positive specimens were titrated and a type-specific PCR using viral
      core gene sequences was used to determine distribution of HCV viral types.
      RESULTS: Eighty-seven percent of the patients were positive in ELISA. All the
      positives but 2 were either positive of indeterminate in RIBA. The frequency of
      indeterminate RIBA results was 33% among HIV-positive subjects and less than 1%
      among HIV-negative ones. PCR was positive in 68% of 73 RIBA-positive or 
      indeterminate individuals and negative in all HCV-seronegative individuals
      examined. No significant differences were observed in HCV viral type, prevalence
      or titers of viraemia between HIV-positive or -negative patients. CONCLUSIONS:
      The majority (68%) of anti-HCV-positive haemophiliacs examined in this study had
      HCV RNA in their sera and anti-HCV profile determined by RIBA had no apparent
      influence on viraemia. The presence of HIV infection in these patients had no
      significant impact on HCV RNA prevalence, titer or HCV type distribution.

PMID- 15566750
TI  - HCMV strain comparison by restriction analysis of genomic virus DNA and of a PCR
      amplified DNA fragment.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is ubiquitous and a major cause of
      disease in the immunocompromised which include the unborn fetus. HCMV strains are
      closely related and may be difficult to differentiate. OBJECTIVES: To analyze new
      HCMV isolates and highly passaged strains by conventional restriction fragment
      length polymorphism (RFLP) analysis of HCMV DNA and restriction analysis (RA) of
      a PCR-amplified a-sequence fragment to identify epidemiological relatedness.
      STUDY DESIGN: DNA from 14 low-passaged clinical isolates and the high-passaged
      strains S348 and AD169 were analyzed by RFLP analysis of BamHI, PstI or HpaII
      digestion as well as by PCR a-sequence amplification. The laboratory results were
      compared according to epidemiological findings. RESULTS: Of the 14 clinical
      isolates 13 could be distinguished from each other by RFLP analysis. Isolates
      from an infant and its mother had identical restriction fragment patterns. Eight
      of 13 clinical isolates were differentiated from each other by comparing a
      sequence PCR fragments according to length and the presence of cleavage sites for
      6 different restriction enzymes. The mother-infant isolates were identical by the
      a-sequence PCR criteria. All 14 low-passaged isolates differed from the high
      passaged S384 and AD169 strains by both distinguishing approaches. CONCLUSIONS:
      Both RFLP and PCR-amplified a-sequence fragment analysis clearly differentiated
      between low- and high-passaged HCMV isolates and are useful epidemiological tools
      for determining viral strain relatedness.

PMID- 15566751
TI  - Differentiation of primary from secondary anti-EBNA-1-negative cases by
      determination of avidity of VCA-IgG.
AB  - BACKGROUND: Serological techniques are used to determine Epstein Barr virus (EBV)
      etiology of a constellation of signs or symptoms related to lymphadenopathy,
      fever, respiratory tract infection, mononucleosis, hepatitis, thrombocytopenia or
      neurological disorder. Anti-Epstein Barr Nuclear antigen (EBNA)-1 is regularly
      negative during the first 3-4 weeks after the onset of clinical symptoms
      indicating acute EBV infection (primary anti-EBNA-1-negative). It may, however,
      also be negative in immunocompromised convalescent individuals (secondary anti
      EBNA-1-negative) such as tumor patients, HIV-positive patients and transplant
      recipients. OBJECTIVES: The aim of this study was to determine the frequency of
      secondary anti-EBNA-1-negative cases and to find a way to distinguish them from
      primary anti-EBNA-1-negative cases using anticomplementary immunofluorescence
      (ACIF) and enzyme immunoassay (EIA). STUDY DESIGN: All sera sent to our institute
      for EBV serology during one year were routinely tested for Viral Capsid antibody
      (VCA)-IgM, VCA-IgG and anti-EBNA-1. RESULTS: VCA-IgG-positive/anti-EBNA-1
      negative cases (13.5% of total VCA-IgG-positive) comprised 55% primary and 45%
      secondary anti-EBNA-1-negative cases. Detection of secondary anti-EBNA-1-negative
      cases was independent of the method used, i.e., ACIF or EIA. VCA-IgG retained its
      high avidity in secondary anti-EBNA-1-negative cases, whereas primary anti-EBNA-1
      negative cases taken during the early phase of acute infection showed low avidity
      of VCA-IgG. CONCLUSION: Determination of the avidity of VCA-IgG routinely and in
      concert with standard serodiagnosis (VCA-IgG, VCA-IgM, anti-EBNA-1) can enable
      the differentiation of primary and secondary anti-EBNA-1-negative cases.

PMID- 15566752
TI  - Detection of yellow fever virus by polymerase chain reaction.
AB  - BACKGROUND: Yellow fever virus continues to cause major epidemics. A sensitive
      rapid diagnostic test is required to identify cases and contacts in order to
      implement emergency immunization campaigns. OBJECTIVES: To identify YFV envelope
      protein gene fragments, construct a polymerase chain reaction (PCR) assay and
      test its utility in identifying viruses isolated from laboratory and clinical
      specimens. STUDY DESIGN: YFV RNA was transcribed with reverse transcriptase and
      the cDNA amplified by PCR using primers encoding a portion of the viral envelope
      protein gene. The identity of the 482 bp amplified product was confirmed by
      restriction enzyme analysis and by dot blot hybridization with a labelled
      oligonucleotide probe. The assay was tested for sensitivity and specificity on
      isolates from South America and Africa. Detection limits were determined using
      different probe labels. PCR inhibitory effects were analyzed with laboratory and
      clinical specimens. RESULTS: The assay was specific for YFV and did not detect
      any of 15 other flaviviruses. The amplified region was conserved among all 32
      South American and African isolates tested. Four strains from Africa did not
      hybridize with the probe, indicating sequence divergence in the envelope protein
      gene. Samples containing 30 pfu of virus were detected by visual inspection of
      the ethidium bromide stained 482 bp DNA amplimer and 10 pfu were detected with a
      digoxigenin labelled probe. Inhibitory effects of human serum on the PCR were
      overcome by diluting samples 4-fold in buffer. Viral neutralizing antibody in
      experimental samples did not affect the sensitivity of detection. Yellow fever
      virus in serum from experimentally infected Cynomolgus monkeys (10(3.7)-10(7.0)
      pfu/0.1 ml) was detected with signal intensities corresponding to the amount of
      virus in the sample. When YFV was added to normal human serum and held at 27
      degrees C and 80% humidity, the RNA could be detected for up to 3 weeks in
      samples that had no infectious virus. CONCLUSIONS: A PCR assay was constructed
      which detected YFV RNA in isolates from patients infected in South America and
      Africa. This assay is specific for YFV but some African strains were not
      detected. More clinical samples should be tested.

PMID- 15566753
TI  - The effect of rolling and orbital motion on herpesvirus replication in tube
      cultures and shell vials.
AB  - BACKGROUND: Isolation of viruses from clinical specimens remains a viable
      diagnostic manoeuvre but positive isolation rates may be low and time to observe
      cytopathic effects (CPE) may be longer than preferred for optimal management.
      Both shell vial (SV) centrifugation and rolling of conventional tube cultures
      (TC) have been used to enhance the isolation process. OBJECTIVES: To determine
      the effect of rolling and orbital motion on the replication of herpes simplex
      virus (HSV) and cytomegalovirus (CMV) TC and SV. STUDY DESIGN: TC were inoculated
      with HSV or CMV at varying dilutions and subjected to rolling or incubated
      stationary. Samples were selected to determine the impact of motion on viral
      yield, time to CPE according to initial multiplicity of infection (MOI) and stage
      of the infection process. Similar studies were performed with SV centrifuged with
      virus followed by stationary incubation or not centrifuged but incubated on an
      orbital shaker. RESULTS: Rolling HSV-infected TC 383 rotations per minute (RPM)
      (30.2 x g) for 4 days enhanced viral yields by 53-fold over TC without motion.
      The optimal RPM response for HSV replication occurred at 96 RPM (1.9 x g) where
      an 89-fold increase in viral yield was detected, P < 0.01. One-step growth
      studies at 0,2 and 96 RPM demonstrated enhancement of HSV replication at 2 and 96
      RPM. TC infected with HSV at low MOI and rolled at 96 RPM had more CPE-positive
      cultures after 1-3 days than controls. Late in the infection process, no
      differences in CPE-positive were detected between rolled and non-rolled TC.
      Studies with CMV and rolling at 96 RPM resulted in more positive TC and greater
      CPE. SV that were not centrifuged but incubated for 16 h on an orbital shaker had
      significantly more HSV foci than those handled by a conventional SV method.
      CONCLUSION: Our studies indicate that orbital motion and motion yielding a force
      near [Formula: see text] enhances the isolation and growth of HSV and CMV in TC
      and SV.

PMID- 15566754
TI  - HTLV-I infection associated with disease in aboriginal Indians from British
      Columbia: a serological and PCR analysis.
AB  - BACKGROUND: Recent epidemiology studies have demonstrated the presence of HTLV-I
      and its close relative, HTLV-II in several aboriginal populations in North,
      Central and South America but not in Canadian Indian populations. HTLV-II appears
      to be more prevalent than HTLV-I in aboriginal populations of the Americas.
      Recently several clinical cases of HTLV-I associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) and a case of adult T-cell leukemia (ATL) have been
      identified in British Columbian Indians. This data suggests that a new endemic
      area of HTLV-I infection may be present within British Columbian Indian
      population. However, it has recently been shown that HTLV-II may also be
      associated with a neurological disease similar to HAM/TSP. OBJECTIVES: The
      purpose of the work reported here was to demonstrate whether HTLV-I, HTLV-II or
      both were responsible for the diseases seen in the British Columbian Indians.
      STUDY DESIGN: In this study serological and gene amplification techniques were
      used to determine whether HTLV-I or HTLV-II was present in four families and
      three unrelated individuals all from different bands of aboriginal Native Indians
      in British Columbia. In each family, one member had an HTLV-associated disease,
      three cases of HAM/TSP and one case of ATL. Of the three individual aboriginal
      natives unrelated to the four families, two had HAM/TSP while the third was
      asymptomatic for HTLV-associated diseases. RESULTS: This study demonstrated the
      presence of HTLV-I in the aboriginal Indians with disease and in some of their
      family members. HTLV-II was not detected in any of the British Columbian Indians
      tested in this study. CONCLUSIONS: These British Columbian Indians represent the
      first Canadian aboriginal Indians with HTLV-I infection and associated diseases.
      Furthermore, the British Columbian Indian population may represent a previously
      unrecognized endemic population of HTLV-I infection.

PMID- 15566755
TI  - Sequence variation within the carboxyl terminus of the nucleoprotein gene of
      mumps virus strains.
AB  - BACKGROUND: On rare occasions, clinically apparent mumps virus infection and
      meningitis can be caused by vaccine virus as well as wild type strains. This has
      been shown by nucleotide sequencing of short regions of the viral genome.
      OBJECTIVES: We wished to confirm and extended these findings by investigating for
      strain differences within the carboxyl terminus of the nucleoprotein (NP) gene,
      which is known to be highly variable amongst paramyxoviruses in general. STUDY
      DESIGN: A 576 bp carboxyterminal fragment of NP was amplified by reverse
      transcriptase (RT) PCR from several different strains and was sequenced directly.
      RESULTS: Three Urabe vaccine variants and five clinical isolates previously
      classified as Urabe strains revealed the same carboxyterminal pattern for NP.
      Three other isolates and the Leningrad-3 vaccine strain showed characteristic
      differences of up to 5% compared to the Urabe strains, with U/C substitutions
      being predominant. CONCLUSIONS: The carboxyterminal sequence of NP varies
      significantly between mumps virus strains such that it can be used for
      differentiating between vaccine and wild-type isolates.

PMID- 15566756
TI  - Parvovirus B19 infection during pregnancy and development of hydrops fetalis
      despite the evidence for pre-existing anti-B19 antibody: how reliable are
      serological results?
AB  - BACKGROUND: Primary infection with human parvovirus B19 during pregnancy can lead
      to fetal hydrops, abortion, or stillbirth. However, reinfection in the presence
      of pre-existing anti-B19 antibody is generally assumed to have no significant
      effect on the developing fetus. OBJECTIVES: To describe a case of fetal loss at
      28 weeks' gestation associated with parvovirus B19 infection which took place in
      a 26-year-old woman despite the evidence for pre-existing anti-B19 IgG
      antibodies. STUDY DESIGN: A nested-PCR assay for parvovirus B19 DNA was performed
      on maternal and fetal samples. Blood samples were tested by various enzyme
      immunoassays (EIA) for the presence of both anti-B19 IgM and IgG antibodies.
      RESULTS: B19 DNA together with anti-B19 IgG antibody were detected in maternal
      blood at the time of intrauterine fetal demise. Amniotic fluid, chorionic villi
      and various fetal tissues also tested positive for viral DNA. In retrospect,
      presence of anti-B19 IgG antibody, but no viral DNA, was repeatedly demonstrated
      in maternal blood before infection took place. However, the serological results
      differed with the test system used. CONCLUSIONS: Provided that the positive
      serological results are reliable, the presence of anti-B19 IgG in blood samples
      collected as early as four years before pregnancy neither protected the mother
      from reinfection not the fetus from transplacental infection with B19 virus.
      However, discrepant (negative) serological results were also obtained depending
      on the test system used. Therefore, and in the light of the possible severe
      consequences of B19-infection during pregnancy, the means for assessment of the
      significance of anti-B19 titers have to be urgently established by development of
      both qualitative and quantitative anti-B19 IgM and IgG standards.

PMID- 15566757
TI  - Re-examination of the McCoy cell line for confirmation of its mouse origin:
      karyotyping, electron microscopy and reverse transcriptase assay for endogenous
      retrovirus.
AB  - BACKGROUND: The McCoy cell line originally derived from human synovial fluid in
      1955, has been later found useful for cultivation of Chlamydia trachomatis. This
      cell line has been subcultured and exchanged between laboratories for many years.
      In recent years, the McCoy cell line has been widely used in many clinical
      diagnostic laboratories and has been supplied through commercial companies for
      the isolation and identification of Chlamydia trachomatis from clinical
      specimens. OBJECTIVES: Since retrovirus-like particles have been observed in
      McCoy cells and the species of origin of the currently used cell line has not
      been adequately documented, further characterization of McCoy cell line obtained
      from commercial sources was carried out. STUDY DESIGN: This study includes
      karyotypes analysis using G-banding for the confirmation of species origin of
      McCoy cells, electron microscopy for examination of virus particles associated
      with the cells and biochemical assay for reverse transcriptase activity for
      detection of retrovirus. RESULTS: Our results showed by karyotype analysis that
      McCoy cells are of mouse origin. Electron microscopic examination revealed the
      presence of endogenous retrovirus type-A and type-C virions. Biochemical assays
      of culture supernatant fluids from McCoy cells detected reverse transcriptase
      activity which required Mg(2+) ions. CONCLUSIONS: The present study has confirmed
      that McCoy cells currently used by many laboratories are mouse cells, not the
      original McCoy cells derived from human cells. Laboratory workers should be aware
      of the presence of endogenous murine retrovirus in this cell line and appropriate
      precautions should be taken.

PMID- 15566758
TI  - Comparison of the rapid second generation directigen EIA with cell culture and
      immunofluorescence for the detection of respiratory syncytial virus in
      nasopharyngeal aspirates.
AB  - BACKGROUND: A second generation-RSV enzyme immunoassay (EIA) was compared with
      cell culture and immunofluorescence to determine the improved efficacy of this
      reformulated system. OBJECTIVES: This study was performed to identify whether the
      EIA might serve an ancillary function during non-operational virology hours, or
      whether the EIA may serve as a replacement of the commonly used direct
      fluorescent assay (DFA). STUDY DESIGN: During the 1992-1993 (September-April) RSV
      season, 124 freshly collected nasopharyngeal (NP) aspirates were tested by the
      EIA and the DFA for the presence of antigen to the infectious agent. Infectivity
      was performed by tube culture cytopathic effect (TC-CPE) in parallel with the two
      antigen detection methodologies. RESULTS: Thirteen of the 48 confirmed positive
      specimens (27%) failed to yield infectious virus by TC-CPE. The sensitivity,
      specificity, positive and negative predictive values of the EIA were 90, 95, 91
      and 94% respectively. This observed sensitivity of 90% using freshly collected NP
      aspirates, represents a marked improvement over an earlier generation EIA kit.
      CONCLUSIONS: Considering the simplicity and speed of this EIA (10 min), the test
      is recommended for use by medical personnel when facilities for DFA and
      traditional virus culture are not readily available.

PMID- 15566759
TI  - A poliovirus type-specific IgM antibody-capture enzyme-linked immunosorbent assay
      for the rapid diagnosis of poliomyelitis.
AB  - OBJECTIVES: To develop and evaluate an IgM antibody-capture ELISA for the rapid
      detection of poliovirus type-specific IgM antibodies in serum and CSF of patients
      suspected of poliomyelitis. STUDY DESIGN: The assay uses monoclonal antibody to
      human IgM as catching antibody, monovalent IPV as antigen and type-specific
      monoclonal antibodies labeled with horseradish peroxidase as detecting antibody.
      RESULTS: Sera from 21 of 24 patients, contacts of these patients or recently
      vaccinated children were positive in the IgM assay. Sera from 100 healthy
      individuals were negative in all three poliovirus type-specific ELISAs. Sera from
      5 of 81 patients with non-polio viral infections showed (weak) reactivity in one
      or more of the IgM assays. In a prospective study, sera and/or CSFs from 72
      patients with a recent clinical diagnosis of poliomyelitis were tested. A
      homotypic IgM antibody response was found in 51 of the 55 patients which shedded
      wild poliovirus in stool or throat. Poliovirus type-specific IgM antibodies were
      also detected in serum from 13 of the 17 patients, from whom no poliovirus was
      isolated. Poliovirus type-specific IgM-antibodies could be detected from the
      second day up till at least 28 days after onset of paralysis. BACKGROUND:
      Poliovirus infections still create measurable morbidity and mortality in the
      world. Rapid diagnosis methods are needed to detect infection. CONCLUSION: The
      use of the poliovirus type-specific IgM antibody-capture ELISA allows rapid
      diagnosis of poliomyelitis within 24 h after obtaining serum or a CSF specimen.

PMID- 15566760
TI  - Nested PCR for detection of BK virus and JC virus DNA.
AB  - BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK
      virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI
      restriction enzyme was located in teh JCV amplimer and cleavage was used to
      differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens
      from 17 bone marrow recipients with haemorrhagic cystitis and one liver
      transplant patient were tested for the presence of BKV and JCV DNA. Four brain
      tissue specimens (paraffin embedded brain tissues and a fresh frozen brain
      biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant
      patient, all with progressive multifocal leukoencephalopathy (PML), were also
      examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each
      virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant
      patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from
      patients with PML. CONCLUSION: Our results show that the nested PCR is a
      sensitive and rapid assay that can be used for diagnosis of BKV and JCV
      infections.

PMID- 15566761
TI  - A multicentric seroepidemiological survey of HTLV-I/II in Italy.
AB  - BACKGROUND: Several studies carried out in the USA and in Europe have shown the
      presence of HTLV-I/II antibodies in subjects belonging to high-risk groups for
      HIV infection as well as blood donors. Concern about the presence of HTLV-I/II
      markers in the normal population, as well as the efficient transmission of HTLV
      I/II by whole blood or infected blood cells have led several countries to include
      screening for anti-HTLV-I/II among the mandatory serological testing of blood
      donors. OBJECTIVE: In order to assess the risk of HTLV-I/II infection related to
      blood transfusions, a multicentric survey for antibodies against HTLV-I and HTLV
      II was carried out involving 10 Italian sites during the spring of 1991. STUDY
      DESIGN: Serum specimens were collected from 14,598 blood donors, 1,411 injecting
      drug users, 1,015 thalassemics, 142 hemophiliacs and 138 hemodialysis patients.
      HTLV antibodies were detected by a screening EIA which combines a viral lysate
      with a recombinant HTLV-I env protein (p21e). The serological confirmation was
      performed by a semi-automated dot-blot immunoassay that detects gag p19 and p24
      and env p21e specific antibodies, while the discrimination of HTLV-I and HTLV-II
      reactivities was carried out by EIAs employing synthetic peptides of the ENV
      region specific for each virus. RESULTS: The seroprevalence of confirmed
      positives was 0.034% among blood donors and 3.61% among IDUs, while no sample of
      the other categories could be confirmed, although several were indeterminate and
      one thalassemic reacted against HTLV-I on peptide testing. HTLV-I reactivity was
      observed in one blood donor, while all 38 of the 51 confirmed seropositive IDU's
      reacted only to the HTLV-II synthetic peptide. CONCLUSIONS: These data confirm a
      high prevalence of HTLV-II among Italian IDUs and show an HTLV-I/II
      seroprevalence among blood donors very similar to that which was found in the USA
      volunteer blood donors. A surveillance program among blood donors seems advisable
      in order to establish the possible need of a mandatory screening for HTLV-I/II.

PMID- 15566762
TI  - Recombinant rubella E1 fusion proteins for antibody screening and diagnosis.
AB  - BACKGROUND: Until rubella is eradicated there will be a continuing need for
      rubella antibody surveillance. Antigen production using recombinant DNA
      technology may be a viable alternative to traditional techniques of producing
      antigens for enzyme immunoassays (EIAs). OBJECTIVES: To investigate the potential
      of bacterial fusion proteins containing rubella E1 protein sequences for use in
      EIAs to detect rubella antibodies. STUDY DESIGN: Purified bacterial fusion
      proteins containing rubella E1 sequences to be used as antigens in EIAs and
      compared to 'traditional' assays using virus derived antigens for rubella
      antibody screening. RESULTS: cDNA clones coding for the complete rubella E1
      protein sequence and subfragments of E1 were modified for expression as carboxy
      terminal fusions with either beta-galactosidase or glutathione-S-transferase.
      beta-galactosidase fusions with the complete E1 coding sequence or amino acids
      201 to 307, which contain known epitopes, resulted in the production of
      predominantly insoluble fusion proteins unsuitable for use in EIA. Nine
      glutathione-S-transferase-E1 fusion proteins were produced with individual fusion
      proteins exhibiting varying properties with regard to the levels of protein
      produced, apparent stability, solubility and the potential for affinity
      purification using glutathione agarose. Reduction of the E1 component to only 44
      amino acids containing three B-cell epitopes (Terry et al., 1988) produced an
      abundant soluble GST-E1 fusion protein (3.5 mug/ml), which could be affinity
      purified using glutathione agarose. This fusion protein has been successfully
      used in EIA to detect rubella antibodies. CONCLUSIONS: We have shown that GST-E1
      fusions have potential as antigens in tests for rubella antibodies.

PMID- 15566763
TI  - Antigen detection in human respiratory Coronavirus infections by monoclonal time
      resolved fluoroimmunoassay.
AB  - BACKGROUND: The diagnosis of respiratory infections by detecting viral antigens
      has received considerable attention using immunofluorescent assays (IFA) and
      enzyme immunoassays (EIA). Time-resolved fluoroimmunoassay (TR-FIA) has been
      developed for several viruses. OBJECTIVES: To prepare monoclonal antibodies to
      coronavirus strains, to incorporate them into a TR-FIA, and test the assay on
      clinical specimens. STUDY DESIGN: Monoclonal antibodies were prepared to the N
      nucleoprotein of the two human respiratory coronaviruses, HCV strains 229E and
      OC43. Monoclonals to both viruses were completely type-specific; they did not
      cross-react between themselves or with multiple strains of other respiratory
      viruses. These antibodies were configured into optimized EIA and TR-FIA tests.
      The all-monoclonal tests were then compared to polyclonal EIA tests in terms of
      their ability to detect virus in clinical specimens. RESULTS: The all-monoclonal
      TR-FIA was uniformly the most sensitive, detecting virus in all 13 229E-positive
      specimens compared to 69% for the monoclonal EIA and 54% for the polyclonal EIA
      test. Similar results were obtained for 10 OC43-positive specimens: 100% in TR
      FIA, 90% in monoclonal EIA, and 80% in polyclonal EIA. For 229E in TR-FIA, mean
      positive/negative (P/N) ratios were 143 for 229E-positive human embryonic lung
      fibroblast (HLF) cell culture fluids and 10 for positive nasopharyngeal aspirate
      specimens; for OC43 in TR-FIA, mean P/N values were 964 for OC43-positive
      rhabdomyosarcoma (RD) cell culture fluids and 174 for positive NPA specimens. The
      sensitivities of the TR-FIA were determined with purified virions to be 0.308 ng
      virus per well for HCV-229E and 0.098 ng virus per well for HCV-OC43.
      CONCLUSIONS: This rapid and sensitive test appears to be much more sensitive than
      traditional antigen detection assays but will require more extensive field
      testing on clinical specimens.

PMID- 15566764
TI  - Identification of influenza A virus by shell vial culture and two commercially
      available antigen detection methods.
AB  - BACKGROUND: Influenza continues to be a major cause of morbidity and mortality
      especially in the elderly and persons with underlying disease. Shell vial cell
      culture and antigen detection techniques may speed up diagnosis and enable better
      patient treatment and management. OBJECTIVES: To compare shell vial
      centrifugation culture with commercially available direct fluorescence and enzyme
      immunoassay kits using a variety of respiratory specimens. STUDY DESIGN: To
      detect influenza A virus, we compared direct fluorescent antibody (DFA) staining
      using the Bartels Viral Respiratory Panel and the Directigen FLU-A enzyme
      immunoassay (EIA) with shell vial centrifugation culture. Ninety-seven fresh
      specimens from a variety of respiratory sources, and transported from hospitals
      throughout the U.S. to our national referral laboratory, were tested. RESULTS:
      Fifteen specimens were true positives: culture positive or both antigen tests
      positive. Sensitivity with culture was 93%, EIA 67%, and DFA 47%. Specificity was
      excellent with all three methods: 100%, 98%, 99%. Culture detected additional
      viruses that can cause respiratory tract disease: herpes simplex,
      cytomegalovirus, respiratory syncytial, influenza B, and adenovirus. Fourteen
      (70%) of 20 frozen specimens previously positive for influenza A were positive on
      retest by EIA. Overall sensitivity of EIA compared with culture using 35 positive
      specimens was 69%. CONCLUSIONS: The rapid EIA is useful to screen for influenza
      A, but critical antigen-negative specimens should be submitted to a virology
      laboratory for culture. Shell vial cultures can provide a sensitive and universal
      diagnostic system for influenza A and a variety of other viruses.

PMID- 15566765
TI  - Detection of Japanese encephalitis virus antigens in the CSF using monoclonal
      antibodies.
AB  - BACKGROUND: Antigen detection in the CSF is an invaluable tool in the diagnosis
      of viral infections of the nervous system, especially in the early phase of the
      illness. Very little information is available on the use of antigen detection in
      the diagnosis of Japanese encephalitis (JE). OBJECTIVES: Evaluation of two
      monoclonal antibody-based antigen detection methods in the diagnosis of JE in
      comparison with the detection of virus-specific IgM antibodies in the CSF. STUDY
      DESIGN: In this study 115 patients with a clinical diagnosis of JE were
      investigated. A reverse passive haemagglutination test for the detection of
      soluble JEV antigens, an immunofluorescent assay for the detection of cell
      associated antigen and an IgM capture ELISA for the detection of virus specific
      IgM antibodies in the CSF were used. RESULTS: Laboratory confirmation of JE was
      possible in 92/115 patients. Virus-specific IgM was detected in 75/92 and JEV
      antigen was detected in 52/92 patients. Soluble antigen was detected in 37/52,
      cell-associated antigen in 30/52. There was no significant difference in the
      sensitivity of the two antigen detection systems used. CONCLUSIONS: Diagnosis by
      antigen detection could be done less frequently than by demonstration of virus
      specific IgM antibodies in the spinal fluid. However, antigen detection proved
      useful during the first week of illness when IgM antibodies were not detected in
      the CSF.

PMID- 15566766
TI  - Viral pathogens and clinical manifestations associated with acute lower
      respiratory tract infections in children of the Sudan.
AB  - BACKGROUND: Incomplete knowledge regarding the viral agents causing respiratory
      infections in children living in developing countries impedes diagnosis and
      management of patients. OBJECTIVES: To assess the role of viral pathogens in
      Sudanese children presenting with acute lower respiratory tract infections
      (ALRI). STUDY DESIGN: The study population consisted of patients presenting with
      ALRI at the Children's Emergency Hospital in Khartoum during 2 periods (December
      1987 to April 1988 and September 1990 to March 1991). Identification of viral
      infections was based an antigen detection by immunofluorescence and enzyme-linked
      immunosorbent assay (ELISA) on nasopharyngeal secretions and/or serology.
      RESULTS: After exclusion of children with measles, 102 and 111 children,
      respectively, were prospectively enrolled in the study during the 2 periods.
      Their ages ranged between one mouth and 14 years (mean 2.0 years). Radiologic
      pulmonary infiltrations were detected in 135 (66%) of the 206 patients who had
      chest radiographs, whereas 7 (3%) showed lobar pneumonia. The case fatality rate
      was 2.3%. Of 83 virus infections detected, 79 were in children < years and
      consisted mainly of respiratory syncytial virus (RSV, 28%), followed by
      parainfluenza (7%), adenovirus (5%) and influenza A (2%). Infiltrates on
      radiographs were significantly less often found in virus-infected cases than in
      ALRI-cases with negative virus tests. CONCLUSIONS: RSV predominantly infected
      young infants (</= 3 months) compared with those who were 5 years or older (28%
      and 13%, respectively). A tendency for respiratory viruses to be more prevalent
      was seen during the cooler months (January and February). There were no
      significant differences in clinical features between virus-positive cases and
      others. The panorama of viral infections proved to be the same as in other
      developing countries.

PMID- 15566767
TI  - Nested PCR for detection of BK virus and JC virus DNA.
AB  - BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK
      virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI
      restriction enzyme was located in the JCV amplimer and cleavage was used to
      differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens
      from 17 bone marrow recipients with haemorrhagic cystitis and one liver
      transplant patient were tested for the presence of BKV and JCV DNA. Four brain
      tissue specimens (paraffin embedded brain tissues and a fresh frozen brain
      biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant
      patient, all with progressive multifocal leukoencephalopathy (PML), were also
      examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each
      virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant
      patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from
      patients with PML. CONCLUSION: Our results show that the nested PCR is a
      sensitive and rapid assay that can be used for diagnosis of BKV and JCV
      infections. The cerebrospinal fluid appears to be a suitable material for
      diagnosis of JC virus reactivation in the brain.

PMID- 15566768
TI  - Generation of hydrogen peroxide by varicella-zoster virus-stimulated
      polymorphonuclear leukocytes.
AB  - BACKGROUND: In varicella-zoster virus (VZV) infections, the initial response in
      cutaneous lesions is predominantly polymorphonuclear leukocytes (PMN). However,
      interaction of VZV and PMN has not yet been fully defined. OBJECTIVES: To explore
      the potential role of PMN in VZV infections, we investigated the ability of PMN
      to generate hydrogen peroxide (H(2)O(2)) after stimulation with VZV antigen.
      STUDY DESIGN: H(2)O(2), one of the reactive oxygen species, was measured by
      cytofluorography after PMN were incubated with varicella-zoster virus (VZV)
      antigen in the presence of seropositive or seronegative serum. RESULTS: H(2)O(2)
      was detectable in unseparated PMN obtained from seropositive children and adults,
      while unseparated PMN of seronegative donors were not capable of generating
      H(2)O(2). Separated PMN obtained from either seropositive or seronegative donors
      were capable of generating H(2)O(2) in the presence of seropositive serum.
      However, H(2)O(2) was not detectable in separated PMN of seropositive donors in
      the presence of seronegative serum. The of H(2)O(2) generation did not correlate
      with concentrations of serum antibodies to VZV. CONCLUSIONS: VZV antigen-antibody
      complexes might induce H(2)O(2) generation by PMN.

PMID- 15566769
TI  - Detection of antibody to HIV in saliva: a brief review.
AB  - BACKGROUND: The possibility that saliva could be used for HIV screening and
      diagnosis has been known since 1986. Despite the obvious advantages over
      venepuncture of ease of collection, safety, compliance and cost, interest in
      salivary testing has grown relatively slowly. Several studies have demonstrated
      that salivary anti-HIV testing can be highly accurate, particularly if specimen
      collection procedure are optimal. OBJECTIVE: To review current knowledge about
      the detection of anti-HIV in oral fluids, with an emphasis on the identification
      of optimal procedures. STUDY DESIGN: In the light of existing published data, the
      factors leading to accurate salivary diagnosis of HIV infection were identified
      and reviewed. RESULTS: To achieve the best results it is essential to collect
      oral fluid specimens that are rich in IgG. Most IgG in the oral cavity derives
      from the crevicular space between the gums and the teeth, and not from salivary
      glands. Available methods for collecting salivary specimens are discussed. Until
      these collection methods are fully validated, individual specimens or at least
      clinical ones found anti-HIV negative should be tested for total IgG before being
      reported on. There is a lack of proven confirmatory methods for salivary anti-HIV
      and this problem is reviewed. Salivary anti-HIV testing has been employed mostly
      for surveillance, but life insurance applicants are increasingly screened in this
      way and clinical applications are under active consideration. With appropriate
      safeguards, diagnostic and pre-blood donation salivary testing could be
      introduced shortly. The necessary technology is also available to develop rapid
      single-use salivary tests. This would bring anti-HIV testing closer to the
      patient. CONCLUSIONS: Salivary tests for anti-HIV offer advantages of
      convenience, economy and safety, and are more acceptable to subjects than blood
      tests. Further evaluation of the collection devices and assays, the introduction
      of safeguards against inadequate sampling and the development of suitable
      confirmatory assays are required. When these deficiencies have been met, salivary
      tests may supersede tests on serum for HIV and also other infections.

PMID- 15566770
TI  - Serological diagnosis of cytomegalovirus infection: comparison of 8 enzyme
      immunoassays for the detection of HCMV-specific IgM antibody.
AB  - BACKGROUND: Recently, numerous commercial ELISA kits for the detection of HCMV
      specific IgM antibodies have been developed and are available on the
      international market. OBJECTIVE: The aim of the present study was to compare
      eight different ELISAs for the early serological diagnosis of HCMV infection.
      STUDY DESIGN: A panel of paired sera obtained from patients suffering from
      primary or secondary infection and potential cross-reactive serum samples
      positive for IgM antibodies against other herpesviruses, antinuclear antibody and
      rheumatoid factor were investigated with 5 indirect ELISAs (1-5) and 3 mu-capture
      assays (ELISAs 6-8). RESULTS: The highest sensitivity for IgM detection was
      achieved by a mu-capture assay (ELISA 8) and a traditional indirect ELISA (4).
      Their respective sensitivities were 78.0 and 76.0%. Overall, mu-capture
      immunoassays (ELISAs 6-8) detected HCMV infection earlier than indirect ELISAs (1
      5) and showed a higher sensitivity for antibody detection in dilution series of
      IgM positive serum samples. Whereas ELISAs 1, 2, 5 and 6 showed a specificity of
      100%, the alternative assays were affected by a variable number of false positive
      results obtained by testing potential cross-reactive serum samples. Their
      specificities ranged from 72.0% (ELISA 8) to 96.0% (ELISA 3). CONCLUSION: The
      results of the present study show that recent mu-capture and indirect ELISAs
      permit a relatively sensitive and reliable diagnosis of HCMV infection. Cross
      reactive antigens and interference from antinuclear antibody may limit the
      specificity of commercial kits.

PMID- 15566771
TI  - Identification of influenza A virus by shell vial culture and two commercially
      available antigen detection methods.
AB  - BACKGROUND: Effective use of amantidine and rimantidine for treating patients and
      for reducing transmission requires rapid diagnosis of influenza A. Rapid culture
      methods require 1-2 days to detect influenza A virus. Direct fluorescent antibody
      (DFA) staining and enzyme immunoassay (EIA) can detect influenza A antigen within
      1-4 h. OBJECTIVES: We compared DFA staining using the Bartels viral respiratory
      panel and the Directigen FLU-A EIA with shell vial centrifugation culture. STUDY
      DESIGN: Ninety-seven fresh specimens from a variety of respiratory sources and
      transported from hospitals throughout the USA to our national referral laboratory
      were tested. A true positive was defined as culture positive or both antigen
      tests positive. RESULTS: Fifteen specimens were true positive. Sensitivity with
      culture was 93%, EIA 67%, and DFA 47%. Specificity was excellent with all three
      methods: 100%, 98%, 99%. Culture detected additional viruses that can cause
      respiratory tract disease: herpes simplex, cytomegalovirus, respiratory
      syncytial, influenza B, and adenovirus. Fourteen (70%) of 20 frozen specimens
      previously positive for influenza A were positive on retest by EIA. Overall
      sensitivity of EIA compared with culture using 35 positive specimens was 69%.
      CONCLUSIONS: These results suggest that the rapid EIA is useful to screen for
      influenza A, but that critical antigen-negative specimens should be submitted to
      a virology laboratory for culture for optimal sensitivity and for recovery of
      other viruses.

PMID- 15566772
TI  - Detection of antibodies to varicella-zoster virus using a latex agglutination
      assay.
AB  - BACKGROUND: There is a clinical need to have a rapid and sensitive means to
      identify persons with immunity to varicella-zoster virus (VZV). OBJECTIVES: We
      evaluated a simple-to-perform assay for detecting antibodies to VZV using a
      commercial latex agglutination (LA) test, in which dilutions of test sera were
      added to latex particles that had been coated with VZV glycoprotein antigens.
      STUDY DESIGN: Sera obtained from patients, including recipients of varicella
      vaccine, whose clinical immune status to VZV was known, were tested by LA and the
      results compared to those obtained by a standard indirect immunofluorescence
      assay (FAMA). Using the LA test, long-term persistence of antibodies in leukemic
      and adult recipients of varicella vaccine were determined. RESULTS: The LA test
      compared favorably with FAMA in varicella susceptibles and immunes. 741 acute
      sera were negative and 741 convalescent varicella sera were positive by LA.
      Antibodies to VZV were found to persist for as long as 11 years in most
      recipients of varicella vaccine (n = 145). Geometric mean titers were higher by
      LA than FAMA. Prozone phenomena were noted in about 5% of antibody-positive sera.
      Results from this test are available in less than an hour, and no special
      equipment is required. CONCLUSIONS: This assay is rapid, simple to perform, and
      inexpensive. It is particularly useful for identifying individuals who are immune
      to varicella, including those who have been immunized in the distant past. The
      main problem associated with the test is that prozone phenomena can occur; these
      may be avoided by testing sera at various dilutions.

PMID- 15566773
TI  - Detection of respiratory syncytial virus infection in nasal aspirate samples by
      flow cytometry.
AB  - HYPOTHESES: (i) Flow cytometry has the potential for rapid detection of
      respiratory viral antigens. (ii) This technique can be applied to viral diagnosis
      in clinical samples. OBJECTIVES AND STUDY DESIGN: (i) To study the identification
      of six common respiratory viral pathogens by flow cytometry, in virus infected
      and uninfected cultured cells, as models of positive and negative clinical
      samples. (ii) To compare flow cytometry with the established techniques of viral
      isolation and immunofluorescent microscopy in the diagnosis of respiratory
      syncytial virus infection in 68 naso-pharyngeal aspirates taken from children and
      sent to the virology laboratory for routine virological diagnosis. RESULTS: (i)
      For each virus analysed, populations of infected and non-infected cells were
      clearly discernable, confirming potential for this method in rapid viral
      diagnosis in clinical samples. (ii) Two definitions were employed for a sample to
      be positive by flow cytometry, these were compared with the combined established
      techniques. The sensitivity, specificity, positive and negative predictive values
      of flow cytometry were 41%, 98%, 92% and 71% for the first definition and 74%,
      88%, 80% and 84% for the second definition respectively. CONCLUSIONS: As tested
      in this study, flow cytometry is less sensitive than established techniques as
      well as recently developed rapid diagnostic techniques for the diagnosis of
      respiratory syncytial virus infection. Further evaluation of the potential of
      flow cytometry in rapid viral diagnosis is warranted.

PMID- 15566774
TI  - Rapid detection of tick-borne encephalitis virus sequences by cDNA amplification
      coupled to a simple DNA enzyme immunoassay.
AB  - BACKGROUND: The tick-borne encephalitis virus (TBEV) causes many cases of severe
      neurological disease in Europe and Asia. Rapid and virus specific laboratory
      tests are needed for epidemiological studies and for diagnosis of human diseases.
      OBJECTIVES: A newly developed colorimetric method, DNA enzyme immunoassay (DEIA),
      was applied to the detection of TBEV-specific sequences. STUDY DESIGN: Reverse
      transcription and polymerase chain reaction (PRC) were used for g genomic
      amplification. The specificity of PCR products was confirmed using an internal
      biotinylated probe from the 5'-NCR immobilized on streptavidin coated microtiter
      wells. The hybridization event was revealed by monoclonal antibodies to double
      stranded DNA in a standard ELISA reaction. RESULTS: A total of 23 TBEV strains
      among them prototype strains and isolates from Germany and other European
      countries was investigated. In all cases hybridization with the internal probe
      has occurred. CONCLUSION: The DEIA described here is a simple and rapid method
      facilitating the handling of a large number of samples and therefore seems to be
      especially valuable to surveillance studies of endemic areas and for diagnosis of
      human diseases.

PMID- 15566775
TI  - Serological survey on hepatitis E virus infection in an endemic area: diagnosis
      potential of enzyme immunoassay for detection of IgG antibody.
AB  - BACKGROUND: Hepatitis E is a major cause of acute icteric disease widespread in
      tropical and sub-tropical regions but rarely occurring in industrialized
      countries. Recently solid-phase enzyme immunoassays with recombinant antigens
      have been introduced for diagnosis of this infection. OBJECTIVES: The aim of this
      study was to evaluate the diagnostic potential of a newly developed Abbott test
      for the detection of IgG class antibodies to hepatitis E virus (anti-HEV IgG) in
      hepatitis patients and 'normal' individuals. STUDY DESIGN: Sera taken from
      hepatitis patients and individuals without liver disorders in endemic
      (Kirghizstan and Uzkbekistan) versus non-endemic (Moscow) areas were
      investigated. In parallel IgG class antibodies to hepatitis A virus (anti-HAV
      IgG) were determined by an enzyme immunoassay with native HAV antigen. RESULTS:
      In five groups comprising altogether 86 suspected hepatitis E patients from
      endemic area the rate of anti-HEV IgG seropositivity varied from 85% to 17%. In
      Moscow anti-HEV IgG was found in one patient (who also had acute hepatitis B) out
      of 19. Anti-HEV IgG persisted in an experimentally infected volunteer for at
      least 12 years after the acute disease. Among the individuals without liver
      disorders eight out of 173 (4.6%) showed anti-HEV IgG seropositivity in
      Kirghizstan while there was only one seropositive out of 165 (0.6%) in Moscow. In
      contrast, anti-HAV IgG were frequently present in the residents of both areas: in
      Kirghizstan over 90% of individuals from young age groups already had these
      antibodies; in Moscow the rate of anti-HAV IgG seropositivity constantly
      increased from 31% in the youngest age group to almost 85% in the oldest one.
      CONCLUSION: Prevalence of anti-HEV antibodies was unexpectedly low in endemic
      area; in Moscow anti-HEV IgG was found only in single cases. Anti-HEV IgG
      seropositivity in a single serum sample could be of certain diagnostic value in
      non-endemic areas.

PMID- 15566776
TI  - Human herpesvirus-6-associated malignant lymphoma in a bone marrow transplant
      recipient.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6), the sixth member of the herpesvirus
      family, can infect and replicate in human hematopoetic cell lines and can cause
      various illnesses in humans. HHV-6 has been suggested to be linked to various
      lymhoproliferative disorders. In vitro studies have demonstrated the oncogenic
      potential of HHV-6. The role of HHV-6 in human lymphomas needs to be examined.
      OBJECTIVE: To determine the involvement of HHV-6 in an immunoblastic lymphoma
      which developed in a bone marrow transplant patient, who had HHV-6 viremia. STUDY
      DESIGN: Paraffin-embedded lymphoma tissues were examined for the presence of HHV
      6 by immunohistochemistry, PCR and in-situ hybridization. This is a case report
      investigation. RESULTS: An acute myelogenous leukemia patient received an
      allogeneic bone marrow transplant. He developed human herpesvirus-6 (HHV-6)
      viremia approximately 6 weeks after transplantation and HHV-6 was concurrently
      isolated from his bone marrow. Soon afterward, a large cell immunoblastic
      lymphoma was diagnosed. Complications of this tumor subsequently resulted in the
      patient's death. Periaortic lymph nodes and tumor cells infiltrating the liver
      and kidneys showed the presence of HHV-6 by immunohistochemistry and polymerase
      chain reaction (PCR). Southern blot analysis of the PCR amplified DNAs confirmed
      the presence of transforming pZVH14 DNA sequences of HHV-6 in the tumor tissues.
      Lymph nodes of 6 immunologically intact individuals were negative for HHV-6 by
      immunohistochemistry and PCR analysis. Tumor tissues were negative for EBV DNA by
      in situ hybridization with DNA probes specific for the EBV EBER RNAs. CONCLUSION:
      Our data suggest that HHV-6 may be involved in the pathogenesis of some
      immunoblastic lymphomas.

PMID- 15566777
TI  - Multiple viral infections in the immunocompromised host: recognition and
      interpretation.
AB  - BACKGROUND: During the past decade, diagnostic virology has become an integral
      part of patient management. Concurrent infection with multiple viruses occurs in
      both the healthy and immunocompromised host. Many common viruses result in latent
      infection with the potential for reactivation throughout the life of the host.
      Superimposed on this are transient infections with yet other viruses. OBJECTIVES:
      To review multiple viral infections in immunocompromised hosts, focusing on
      laboratory recognition and interpretation of results. STUDY DESIGN: A review of
      the literature, with case examples from the author's laboratory. RESULTS: Viral
      infections are more likely to cause morbidity and mortality in immunodeficient
      hosts, and early recognition and treatment may be lifesaving. To detect two or
      more viruses shed concurrently from the same body site requires the use of
      multiple test modalities, which are now available in many clinical laboratories.
      Establishing the significance of a virus isolate is a complex process. Knowledge
      of the specimen source, virus quantitation and characteristics of the patient are
      helpful. Careful evaluation of the patient's clinical findings together with
      other laboratory test results, including histopathology, X-rays and the detection
      of other microorganisms, is also essential. CONCLUSIONS: The recognition and
      interpretation of multiple virus infections requires heightened awareness as well
      as close cooperation and communication between the professionals in the
      laboratory and physicians at the bedside.

PMID- 15566778
TI  - Seasonality and prevalence of rotavirus in Al-Ain, United Arab Emirates.
AB  - BACKGROUND: Rotaviruses are the single most important causative agent of acute
      neonatal enteritis in most avian and mammalian species including humans.
      Rotaviruses infections have also been shown to be associated with the elderly,
      immunocompromised individuals and more recently with epidemic diarrheal illness
      in adults. OBJECTIVES: To study the incidence and the effect of seasonality on
      the prevalence of rotaviruses in Al-Ain, United Arab Emirates. STUDY DESIGN: A
      total of 650 stool samples submitted to the laboratories of two University
      Teaching Hospitals (Al-Ain and Tawam) and a private hospital (Oasis) were
      examined for the presence of rotaviruses from January 1990-December, 1992, using
      a commercially available latex agglutination assay. The meteorological data
      (temperature, relative humidity and rainfall) recorded during the sampling period
      was analyzed statistically to examine the effect of seasonality on the prevalence
      of rotavirus cases in Al-Ain, United Arab Emirates. RESULTS: Rotavirus was
      detected in 21.4% of the samples examined. The predominant number of positive
      cases (35%) were in the 7-12 months age group. It was interesting to find
      rotavirus-positive cases in as low an age group as < 3 months (3.6%) and as high
      as 10 years (8.04%). There was no significant difference on infection rates
      between male and female groups in the study. However, there was a significant
      difference between the national (38.18%) and non-national children (61.28%). The
      higher rate of the latter may be due to import of infections. There appeared to
      be a seasonal pattern of rotavirus occurrence in the cases studied, with a marked
      increase in the number of positive cases during the months when the relative
      humidity was low (25-45%) and there was no rainfall. CONCLUSIONS: Rotavirus was
      detected in all age groups with a predominance in 7-12 month age groups, and a
      higher incidence in non-nationals. There was a marked increase in the number of
      positive cases during the months when the relative humidity was low (25-45%) and
      there was no rainfall. These findings are discussed in relation to the
      epidemiology and prophylaxis of rotavirus infections.

PMID- 15566779
TI  - Human parvovirus B19 serology with recombinant VP1 and VP2 antigens: diagnosis of
      acute infections by detecting B19-specific IgM and IgA antibodies.
AB  - BACKGROUND: The availability of immunoassays for the laboratory diagnosis of
      human parvovirus B19 (B19) infection, which is commonly associated with erythema
      infectiosum in children and arthropathy and arthralgia in adults has been
      hampered by the lack of native B19 antigen. The production of abundant supplies
      of recombinant (r) B19 proteins, through the cloning of the B19 genome into
      expression vectors, has led to a proliferation of assays for detecting B19
      specific antibodies. OBJECTIVES: This study was undertaken to evaluate
      serological assays for detecting B19-specific IgM and IgA antibodies using rVP1
      and rVP2 B19 viral coat proteins. Their suitability in the diagnosis of acute B19
      infections and the incidence of non-specific reactivity were determined. STUDY
      DESIGN: A panel of sera consisting of B19-specific IgM-positive and -negative
      samples was tested for B19-specific IgM and IgA antibodies in an indirect IFA
      using rVP1 antigen. These samples and a further panel collected from patients
      with other virus infections and samples containing rheumatoid factor were tested
      for B19-specific IgM in an antibody-capture ELISA and an indirect ELISA, both of
      which utilized rVP2 antigen. RESULTS: Data from the two ELISAs using rVP2 antigen
      and the IFA with rVP1 antigen all showed significant correlation (P >/= 0.001)
      with a reference RIA using native B19 antigen. Non-specific reactions were
      observed with Paul-Bunnell-positive and rubella virus-specific IgM antibody
      positive sera in the ELISAs but not in the IFA. B19-specific IgA antibodies were
      detected in all sera containing B19-specific IgM antibodies but were also found
      in a small number of sera collected from healthy blood donors with no history of
      recent B19 infection. CONCLUSION: This study demonstrates the usefulness of
      assays employing rVP1 and rVP2 B19 antigens for detecting B19-specific
      antibodies. The use of IgM-specific ELISAs allows the processing of large numbers
      of samples and the absence of non-specific reactivity in the IFA may indicate a
      role for this assay as a confirmatory test.

PMID- 15566780
TI  - Anti-HBs kinetics after HBV vaccination in neonates.
AB  - BACKGROUND AND OBJECTIVES: We report the results of a study using a recombinant
      DNA HBV vaccine in newborns from an endemic area for HBV and compare the anti-HBs
      kinetics with observations in adults in order to make estimates about the need
      for booster vaccinations. STUDY DESIGN: One hundred and forty-eight neonates were
      vaccinated and followed for 62 months. Based on the presence or absence of
      hepatitis B surface antigen in the mother, cohorts of 'exposed' and of 'non
      exposed' neonates were identified. RESULTS: A maximum concentration is normally
      observed after the booster vaccination followed by a rapid decline. According to
      Ambrosch et al. and Gesemann et al., titer calculations as a function of time,
      yielded 37 IU/1 and 47 IU/1 at month 60 respectively. The mean titer for the
      three groups of neonates investigated was at that time 74 IU/1. The prospective
      time intervals to arrive at an anti-HBs level of at least 10 IU/1 can be
      individually calculated from the individual titer after the booster vaccination.
      These calculated estimates show respectively: that 8.3% of the vaccinated
      neonates need a new booster vaccination within 14 months; that 26.7% will need a
      new booster within 50 months; and that only 65% need a new booster in 50 or more
      months. CONCLUSION: It can be concluded that anti-HBs kinetics in very young
      children and adults are comparable. The least expensive way of maintaining
      protection against HBV in neonates seems to be the determination of the
      individual titers after the first booster vaccination and calculation of the
      prospective time interval to arrive at a minimum titer of 10 IU/1 and the need
      for a new booster vaccination.

PMID- 15566781
TI  - Rubella reinfection; role of neutralising antibodies and cell-mediated immunity.
AB  - BACKGROUND: Rubella virus may be transmitted to the fetus following rubella
      reinfection in early pregnancy. The mechanisms responsible for maternal-fetal
      transmission in women with pre-existing rubella antibodies are, however, unclear.
      OBJECTIVES: To evaluate the protective role of rubella specific neutralising
      antibodies and cell-mediated immunity in rubella reinfection. STUDY DESIGN:
      Rubella Nt antibodies were measured in sera obtained from: women who experienced
      rubella reinfection during pregnancy, volunteers experimentally challenged with
      rubella vaccine and women attending for routine rubella antibody screening. Cell
      mediated immunity was assessed by measuring rubella specific LT responses among
      women who had experienced rubella reinfection during pregnancy. RESULTS: Some
      women experienced rubella reinfection during pregnancy despite the presence of Nt
      antibodies in sera obtained before contact. Only 2 of 13 (15.3%) volunteers with
      low levels (< 15 IU/ml) of rubella antibody had detectable Nt antibodies prior to
      experimental challenge. Despite this, they did not develop rubella viraemia
      following challenge and virus excretion was detected in only one case, although
      the majority (11/13, 84.6%) demonstrated a significant rise in antibody titre.
      Among pregnant women screened as having a low level of rubella antibody
      antenally, only 37% had detectable Nt antibodies. Among 23 women who experienced
      rubella reinfection during pregnancy 4 months to 6 years (mean 32 months)
      previously, 20 (86.9%) had a positive rubella-specific LT response. Only one of 4
      cases where rubella virus was transmitted to the fetus failed to produce a a
      specific LT response. CONCLUSIONS: This study indicates that rubella reinfection
      is not associated with a lack of Nt antibodies or persistent impairment of
      rubella-specific LT responses.

PMID- 15566782
TI  - Molecular characterization of a human group A rotavirus isolated from an adult
      with severe dehydrating diarrhea and its relationship to strains concurrently
      circulating among children.
AB  - BACKGROUND: While group A rotavirus is widely accepted as an important etiology
      of acute gastroenteritis in children, this agent rarely causes severe diarrhea in
      adults and, thus, is not considered by physicians to be an etiological agent for
      such diseases. OBJECTIVES: None of the reports describing such rare cases in
      adults has examined the causative strains genetically in detail. STUDY DESIGN: We
      determined the G type, the gene 4 genotype, the electropherotype, and the genomic
      RNA constellation (genogroup) of a group A rotavirus strain isolated from an
      adult with severe diarrhea. This patient, the first documented case of rotavirus
      diarrhea in adult in Japan, suffered from severe dehydrating diarrhea with 'rice
      water' appearance, vomiting and little abdominal pain, presenting a clinical
      picture typical of cholera. RESULTS: Rotavirus antigen and genomic RNA were
      detected in the stool but other enteric pathogens including Vibrio cholerae
      responsible for the disease were not isolated. Molecular characterization
      revealed that the patient was infected with a strain of the DS-1 genogroup with
      G2 and gene 4 genotype 4 which was circulating among children during the same
      period. CONCLUSIONS: The result that the same group A rotavirus strain was
      isolated from children and an adult underlines the necessity of examining
      rotavirus in adults with acute diarrhea.

PMID- 15566783
TI  - Current status of the molecular genetics of hepatitis C virus and its utilization
      in the diagnosis of infection.
AB  - BACKGROUND: Since the discovery of hepatitis C virus (HCV) as a major cause of
      non-A non-B hepatitis, advances have been made in our understanding of the
      molecular biology of HCV and its relatedness to the flaviviruses and
      pestiviruses. The use of molecular techniques to construct an antibody assay has
      enabled the accumulation of information concerning the natural history and
      pathogenesis of HCV infection. OBJECTIVES: The objective was to review the
      literature to March 1994 on the structure, function and genetics of HCV and to
      correlate these findings with approaches to diagnosis that have contributed to
      our understanding of HCV infections. STUDY DESIGN: We reviewed the virological
      and medical literature from 1988 to March of 1994 with a focus on the stated
      objectives. RESULTS: Although the structure of HCV has been well-defined, our
      knowledge of the function of all the genes of HCV is incomplete. Structural core
      and envelope proteins as well as enzymes have been described. The 5' end of the
      polypeptide is most conserved. Genotyping of isolates varies according to the
      part of the gene examined. Several genotypes exist and tend to predominate in
      global populations. Antibodies to the various proteins can be measured by EIA
      assays and positive specimens often require confirmatory testing. Uniquely
      sensitive nucleic acid detection systems for RNA amplified by PCR have enabled a
      better understanding of the natural history, epidemiology and responses to
      treatment. CONCLUSIONS: Well-designed studies for the detection of nucleic acid,
      antibodies and antigens using a variety of viral gene products will provide even
      more information about HCV infections and help lead to treatment and prevention.

PMID- 15566784
TI  - Application of ELISA for IgM, IgA and antigen detection for rapid diagnosis of
      respiratory syncytial virus infections: a comparative study.
AB  - BACKGROUND: Infection with Respiratory Syncytial Virus (RSV) can be rapidly
      diagnosed by detection of viral antigen in nasopharyngeal secretions (NPS) or
      serologically by detecting IgM and IgA antibodies. OBJECTIVES: To evaluate the
      above methods for reliability and rapidity, and compare them with the complement
      fixation (CF) test and virus isolation. STUDY DESIGN: Viral antigen was tested in
      145 NPS samples by ELISA in parallel with tissue culture isolation. The geometric
      mean titer (GMT) of complement fixing antibodies in various age groups was
      determined from 92 individual serum samples by CF test. The diagnostic methods,
      CF test, ELISA-IgM and ELISA-IgA, were evaluated using 21 pairs of acute and
      convalescent sera. Appearance of IgM and IgA in serum samples with low or
      negative CF titers was studied in two age groups: 0-10 months (n = 82), and 11
      months-9 years (n = 47). RESULTS: From the 145 NPS samples, 20 samples were
      positive by both ELISA and virus isolation, 9 were positive only by ELISA and 5
      were positive only by virus isolation. The GMT by age group for 92 sera evaluated
      by CF test were 40 (0-10 months), 195 (11-24 months), 269 (2-4 years), 173 (5-12
      years) and 132 (adults). Among the 21 paired sera examined, CF test detected 13
      RSV infections by antibody rise or seroconversion while the ELISA-IgM/IgA tests
      identified all 21 infections, 7 of them in the first sample. The presence of IgM
      alone or IgM and IgA antibodies was demonstrated in both age groups examined;
      however, IgA alone was found only in the age group 11 months and older.
      CONCLUSIONS: ELISA for antigen detection is better than virus isolation because
      it is faster (6-20 h vs. 3-20 days, respectively) and more sensitive (29/34 vs.
      25/34 positives, respectively). ELISA-IgM and ELISA-IgA was more sensitive and
      reliable than the CF test, particularly for the 0-10 month age group. Thus, when
      necessary, serological diagnosis of RSV infection can be based on the presence of
      IgM and/or IgA antibodies in serum samples obtained early after onset of
      symptoms.

PMID- 15566785
TI  - Direct detection and characterization of rotavirus into subgroups by dot blot
      hybridization and correlation with 'long' and 'short' electropherotypes.
AB  - BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) and polyacrylamide gel
      electrophoresis (PAGE) of viral RNA are well-established methods for detection of
      rotavirus in stool samples. Dot-blot hybridization has also been found to be a
      sensitive and specific technique for detection and characterization of
      rotaviruses. OBJECTIVES: To compare the performance of dot blot hybridization
      with ELISA and PAGE for detection of rotavirus in stool samples. To assess the
      use of dot blot hybridization for characterization of rotaviruses into subgroups.
      STUDY DESIGN: Stool samples were collected from 214 children presenting to the
      hospital with acute diarrhoea. These were assayed for rotavirus by ELISA and
      PAGE. Dot-blot hybridization was done with full length cloned radiolabelled c-DNA
      probes of gene segment 6 of SA-11 (subgroup I) and Wa (subgroup II) rotaviruses.
      RESULTS: Out of 214 stool samples 134 were found to be positive for rotavirus by
      one of the three methods. Among these 134 positive specimens 114 were positive by
      dot blot hybridization, this included 18 specimens which were positive only by
      dot blot assay. One-hundred-and-twelve of these 114 specimens could be
      subgrouped. Fifteen of these were classified as subgroup I, 97 as subgroup II and
      two had a dual subgroup specificity. Three subgroup 1 strains had a 'long' RNA
      pattern, whereas one subgroup II strain had a 'short' RNA pattern which has not
      been reported earlier for human rotaviruses. CONCLUSION: Dot blot hybridization
      as described here is a sensitive and specific assay for detection and subgrouping
      of rotaviruses. However, as there is a considerable genomic diversity among
      rotaviruses, the panel should include probes from all the genotypes of gene
      segment 6.

PMID- 15566786
TI  - Evaluation of sexual transmission in patients with chronic hepatitis C infection.
AB  - BACKGROUND: The transmission of hepatitis C virus (HCV) by parenteral exposure is
      well documented. However, a proportion of patients with acute or chronic HCV
      infection have an unknown source of infection. OBJECTIVES: The purpose of this
      study is to evaluate the role of sexual transmission in HCV infection. STUDY
      DESIGN: 68 patients (median age, 50 years) with chronic hepatitis C and their
      spouses were tested for the presence of antibody to HCV (anti-HCV) by multi
      antigen and chimeric C25 antigen enzyme immunoassays and for HCV RNA by the
      polymerase chain reaction. Information on sexual activity and risk factors for
      HCV infection were obtained from all couples via a questionnaire. RESULTS: All
      index patients were positive for both anti-HCV and HCV RNA. Antibody to HCV was
      detected in four (5.9%) of their spouses. One anti-HCV-positive spouse had a
      history of blood transfusion while the other three (4.4%, 95% CI = 1.5-12.2%) had
      no known risk factors for HCV infection and thus may have been exposed to HCV via
      sexual transmission. Two of these 3 spouses had positive serum HCV RNA and had
      identical HCV genotype to the index patients. The length of sexual exposure was
      significantly longer in the couples who both were anti-HCV-positive than in
      patients whose spouses were anti-HCV negative (median: 25 vs. 10 years, P = 0.02,
      Mann-Whitney test). In our 68 index patients, 96% had antibodies to the
      recombinant proteins from the C22 (core) and C33C (NS3) regions, and 82% and 76%
      had antibodies to the proteins from the NS5 and C100-3 (NS4) regions. Identical
      anti-HCV profiles were noted in two of the four anti-HCV-positive couples.
      CONCLUSIONS: Our results indicate that sexual transmission, although uncommon,
      should be considered as a risk factor for HCV infection, especially in spouses
      who have had long-term intimate relationships with a chronic hepatitis C patient.

PMID- 15566787
TI  - Laboratory diagnosis of HCMV-related disease in renal transplant patients - pp65
      antigen detection versus nested PCR.
AB  - BACKGROUND: Sixty-five renal transplant (Tx) recipients were monitored for signs
      and symptoms of human cytomegalovirus (HCMV) infection. OBJECTIVES: Different
      diagnostic markers were evaluated for early and correct diagnosis of HCMV
      disease. STUDY DESIGN: Blood and urine samples were obtained in weekly intervals
      and the following markers were determined: (1) IgG and IgM antibodies in serum
      using immunofluorescence and ELISA tests; (2) viral shedding in urine by rapid
      centrifugation culture (RCC); (3) viral antigen (pp65) in peripheral blood
      leukocytes (PBL) by immunofluorescence and (4) viral DNA in PBL by nested PCR
      (NPCR). RESULTS: Twenty-two patients remained free of HCMV infection, 18 patients
      developed clinical symptoms of HCMV disease, and 25 patients remained
      asymptomatic in spite of laboratory signs of HCMV infection. For the early
      detection of HCMV disease, the highest sensitivity was achieved using NPCR (100%)
      and pp65 antigen detection (94%). RCC and IgM serology were less sensitive (62%
      and 40% respectively). The differences of sensitivity were significant. Clinical
      specificity was 47% for NPCR, 79% for pp65 antigen detection, 66% for RCC, and
      68% for IgM serology. CONCLUSION: In contrast to NPCR, pp65 antigen detection was
      closely correlated with the appearance of clinical disease and proved to be a
      useful marker in the monitoring of antiviral therapy.

PMID- 15566788
TI  - Distribution of HIV genomic DNA in brains of AIDS patients.
AB  - BACKGROUND: Data concerning the distribution of HIV in the brains of AIDS
      patients at different stages of viral infection might contribute towards: (1)
      understanding the route(s) of HIV entry into the brain and virus dissemination
      within the brain and (2) establishing a possible correlation between the extent
      of CNS damage and the distribution of virus in AIDS brains. OBJECTIVE: To
      determine the distribution of HIV-1 genomic DNA within the brains of three
      deceased AIDS patients by polymerase chain reaction (PCR). STUDY DESIGN: The
      brains of three deceased AIDS patients were examined. Two brains had limited
      neuropathologic findings (brains I and II), and one brain (brain III) showed
      primary HIV-specific neuropathologic damage. Tissues were taken from different
      locations within each brain, and high molecular weight DNA isolated from the
      tissues was assessed for HIV-1 genomic DNA by PCR. RESULTS: HIV-1 genomic DNA was
      found in all three brains, but the amount was low: order of magnitude of 1 viral
      genome per 1,000 cells. Multiple PCR analyses of DNA from brain I showed that the
      viral genomic DNA in this brain was non-uniformly distributed; only samples taken
      from the brainstem were clearly positive for HIV-1. HIV-1 genomic DNA in brain II
      was found in portions of the lower and upper hemispheres. All but one of the
      brain III samples were clearly positive for HIV-1, and they had been taken from
      locations spread throughout this brain. CONCLUSIONS: Our results suggest that in
      early or latent stages of HIV-infection of the brain, viral genomic DNA is
      localized at restricted regions. At later stages this DNA is distributed more
      uniformly throughout the brain. Our data are compatible with the concept of rare
      infection events followed by viral spreading within brain tissues.

PMID- 15566789
TI  - Detection of human cytomegalovirus DNA in immunocompromised children by
      polymerase chain reaction.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is a major complication in
      immunocompromised patients, such as those with leukemia, acquired
      immunodeficiency syndrome (AIDS) and allograft recipients. A sensitive and
      specific diagnostic procedure of CMV infection is required. The polymerase chain
      reaction (PCR) procedure has been demonstrated to be more sensitive than
      conventional virus isolation. However, CMV DNA can be detected in patients with
      latent or asymptomatic infections by PCR because of its extreme sensitivity.
      OBJECTIVES: In this study, we used PCR and reverse transcription PCR (RT-PCR) to
      detect CMV DNA and mRNA in immunocompromised patients and evaluated the value of
      PCR and RT-PCR for diagnosis of active CMV infection. STUDY DESIGN: We examined
      thirty immunocompromised children for CMV DNA using peripheral blood mononuclear
      cells (PBMC), polymorphonuclear leukocytes (PMNL). urine and throat swabs from
      October 1991 to March 1992. Eighteen of the patients had acute lymphoblastic
      leukemia, four had non-Hodgkin's lymphoma, two had Wilms' tumor and six were
      recipients of an allogeneic bone marrow transplantation. Four patients developed
      CMV-related clinical symptoms during the observation period: two patients with
      pneumonia and two patients with hepatitis. RESULTS: CMV DNA was detected in four
      patients with clinical symptoms and in five patients without evidence of CMV
      infection. The incidence of CMV DNA was significantly higher in symptomatic
      patients than asymptomatic patients. CMV mRNA encoding the late antigen was
      detected by RT-PCR only in patients with clinical symptoms of CMV infection.
      CONCLUSIONS: We concluded that detection of CMV DNA by PCR is of little clinical
      significance for distinguishing latent form active CMV infection. It is suggested
      that detection of CMV mRNA by RT-PCR is useful for diagnosis of active CMV
      infection.

PMID- 15566790
TI  - Identification of enteroviruses by indirect immunofluorescence using monoclonal
      antibodies.
AB  - BACKGROUND: Serum neutralization (Nt) is used most often to type enterovirus
      isolates, but it is labor-intensive, expensive, and supplies of reference
      antisera for Nt are limited. Alternative methods of enterovirus typing are
      needed. OBJECTIVES: To investigate the use of indirect immunofluorescence (IFA)
      with commercially available monoclonal antibodies (MAbs) as an alternative to Nt
      for the identification of enteroviruses. STUDY DESIGN: Two MAb blends (one for
      coxsackie B viruses and one for echoviruses 4, 6, 9, 11, 30, and 34) and a
      coxsackie A9 MAb were used to screen 465 clinical isolates over a period of two
      years. Virus isolates which tested positive with one of the blends were typed
      with the individual MAbs of the respective blend. Individual MAbs for
      polioviruses 1, 2, and 3 acquired late in the study were used to screen 45 viral
      isolates. RESULTS: The antibodies identified 251/465 (54%) of the total number of
      isolates tested. IFA results for 451 of 465 viral isolates were in agreement with
      conventional identification methods. The sensitivity of the IFA screen using the
      MAb blends and coxsackie A9 MAb was 93% and the specificity was 99%. Thirteen
      discrepant isolates were negative by IFA, with twelve positive by Nt for
      echovirus 30 and one isolate positive by Nt for coxsackie A9. The remaining
      discrepant isolate was positive by IFA for both coxsackie A9 and coxsackie B5,
      but positive by Nt for coxsackie A9 only. CONCLUSIONS: IFA is highly specific for
      the identification of enteroviruses, but may not be sensitive enough to identify
      all strains within an enterovirus type. Procedures which utilize an IFA screen
      and confirm final results by Nt decrease turnaround time and reduce the number of
      cell culture tubes required for the identification of each enterovirus isolate.

PMID- 15566791
TI  - Quantitative PCR for the measurement of circulating proviral load in HIV-infected
      individuals.
AB  - BACKGROUND: PCR has been applied extensively as a tool for the detection of HIV.
      We have previously developed a semi-quantitative microtiter plate assay for the
      specific detection of HIV PCR products. OBJECTIVE: To develop and evaluate a
      novel quantitative assay for the measurement of circulating proviral load in HIV
      infected individuals. STUDY DESIGN: We evaluated 70 consecutive, unselected HIV
      infected patients, divided into 3 groups, according to their CD4 cell count:
      greater than 500 cells/microl (10 subjects); 200-500 cells/microl (31 subjects);
      less than 200 cells/microl (29 subjects). Peripheral blood mononuclear cell
      lysates were amplified, and a portion of the product was added to streptavidin
      coated wells with a biotinylated capture probe and a horseradish peroxidase
      linked reporter probe, complementary to separate regions of the amplified
      product. Following incubation, readings were taken with an automated plate
      reader. Products were quantitated by interpolation into a standard curve of
      serial dilutions of an HIV-containing plasmid, included in each assay. RESULTS:
      HIV sequences were detected in all 70 clinical samples. Within each patient
      category, a wide range of proviral loads were observed. However, proviral
      load/10(6) CD4 cells was associated with disease progression when the patient
      groups were considered (up to 9.6% infected cells in subjects with CD4 cell
      counts below 200/microl). CONCLUSIONS: This quantitative PCR assay will allow the
      measurement of proviral load in clinical samples. It may be useful in the
      managment of HIV-infected individuals and the evaluation of the efficacy of
      antiretroviral therapy.

PMID- 15566792
TI  - Genotyping of hepatitis C virus by a simple ELISA method.
AB  - BACKGROUND: Hepatitis C virus (HCV) has been classified into five distinct types
      by nucleotide sequence analysis of the genome. The correlation between genotypes
      of HCV and sensitivity to treatment or prognosis is still controversial.
      OBJECTIVES: We tried to establish a simple antibody assay to determine the HCV
      serotype instead of genotype determined by PCR or nucleotide sequence. STUDY
      DESIGN: We made an enzyme-linked immunosorbent assay (ELISA) system by using
      synthetic oligopeptides of NS4 regions of types 1 (CH) and 2 (KN) HCV, and
      examined sera of various stages of hepatitis C patients. RESULTS: Among 13 HCV
      RNA-positive sera, serotyping was consistent with genotyping. Four sera of type 1
      and 7 sera of type 2 were positive to anti-CH and anti-KN antibodies,
      respectively. Two sera of patients mixedly infected with type 1 and 2 HCV were
      positive to both antibodies. The number of type 1 and 2 in patients with chronic
      hepatitis, liver cirrhosis and hepatocellular carcinoma was 27 and 18, 28 and 15,
      and 46 and 12 respectively. CONCLUSIONS: Our result suggests that this simple
      ELISA method is useful for typing of HCV, and there is no significant
      relationship between HCV type and liver failure.

PMID- 15566793
TI  - Multi-organ donor transmission of hepatitis C virus to five solid organ
      transplant recipients and lack of transmission to corneal transplant recipients.
AB  - BACKGROUND: A multi-organ donor seronegative for hepatitis C virus (HCV) by 1st
      generation enzyme immunoassay (EIA) supplied 5 solid organs and 2 corneas to 7
      recipients. This donor was retrospectively shown to be 2nd generation HCV EIA
      positive and polymerase chain reaction (PCR)-positive. All 5 solid organ
      recipients but none of the corneal recipients developed HCV infection.
      OBJECTIVES: To demonstrate the discordance between serological and PCR-based HCV
      detection in solid organ transplant recipients and the lack of transmission of
      HCV to the two corneal transplant recipients. STUDY DESIGN: All 5 solid organ
      recipients were retrospectively shown to be HCV PCR-negative and -seronegative
      pre-transplant and HCV PCR-positive post-transplant. Serial serum samples on 3
      recipients were evaluated by 2nd generation EIA, a prototypic structural and non
      structural dual bead assay (EIA-SA, Abbott), the Chiron Recombinant Immunoblot
      Assay, 2nd generation (RIBA-2), and the Chiron RIBA HCV Test System Strip
      Immunoblot Assay 3.0 (RIBA-3, Chiron). RESULTS: The dual bead EIA-SA and RIBA-3
      were able to detect HCV seroconversion approximately 6 months earlier than the
      2nd generation EIA in 2 recipients, and in 1 recipient only PCR detected
      infection within the first 10 months. There was no evidence of HCV transmission
      to the corneal recipients. CONCLUSIONS: Although third generation assays such as
      the RIBA-3 and EIA-SA narrowed the window of HCV seronegativity in transplant
      recipients compared with the 2nd generation EIA, PCR was the most sensitive
      method of detecting acute HCV infection. Despite transmission of HCV to all of
      the solid organ recipients HCV was not transmitted to the corneal transplant
      recipients.

PMID- 15566794
TI  - No direct relationship between HIV1/2 infection and HHV-6 antibody response in a
      large-scale European and African trial.
AB  - BACKGROUND: Tropism of both human herpesvirus-6 (HHV-6) and human
      immunodeficiency virus (HIV) for CD4+ lymphocytes, and several studies on HIV
      enhancer transactivation by HHV-6 have suggested that HHV-6 could be implicated
      as a cofactor in the progression of HIV infection to AIDS. OBJECTIVES: To
      determine if there is any relationship between HHV-6 infection and the course of
      HIV infection. STUDY DESIGN: 527 French and 558 African sera (210 from Senegal,
      348 from Ivory Coast) were tested for HHV-6 titers by immunofluorescence assay
      (IFA). For each country, patients studied were divided into several groups; those
      with AIDS, those who were HIV-seropositive but symptomless, and HIV-seronegative
      patients. RESULTS: No statistical difference could be found between HHV-6
      prevalences or HHV-6 geometric mean titers obtained for each geographical area in
      the different HIV-1- and/or HIV-2-positive and HIV-negative groups. HIV patients
      with clinical manifestations of AIDS did not differ in percent seropositivity or
      distribution of titers from the HIV-asymptomatic patients or HIV-seronegative
      patients. CONCLUSION: These findings suggest that there is no correlation between
      HHV-6 antibodies and HIV seropositivity or with the stage of HIV infection.

PMID- 15566795
TI  - HIV p24 antigen concentration in serum of 11 anti-HIV 1-positive patients before
      and after immune-complex dissociation: a study of a 5-year period.
AB  - BACKGROUND: Determination of the p24 antigen of the human immunodeficiency virus
      type 1 (HIV 1) is widely used to monitor viral activity though it is well known
      that substructures with p24 specificity present in serum can be complexed with
      specific antibodies, thereby preventing them from being detected by regular p24
      antigen detection assays. OBJECTIVES: To compare the regular assay for p24
      antigen with a procedure that dissociates immune-complexes before determination
      of this antigen. STUDY DESIGN: Eleven HIV 1-infected patients were followed for
      up to 5 years in order to obtain continuity in terms of the development of the
      p24 antigen in comparison with other surrogate markers. RESULTS: The results show
      that even low concentrations of anti-p24 antibodies are able to complex p24
      antigens, rendering them undetectable in the routine assay. p24 antigens became
      detectable only after dissociation of these immune complexes by acid treatment
      procedure. In most patients viral activity became demonstrable only after
      application of the dissociation procedure.

PMID- 15566796
TI  - CMV PCR monitoring in leucocytes of transplant patients.
AB  - BACKGROUND: The presumed latency of cytomegalovirus (CMV) in leucocytes and the
      sensitivity of the polymerase chain reaction (PCR) raise a question of its
      clinical value. OBJECTIVES: To develop and standardize a CMV PCR as a diagnostic
      tool for CMV infection in solid organ and bone marrow transplant patients by
      comparing it to a likewise standardized isolation, rapid isolation and to
      clinical symptoms. STUDY DESIGN: The material comprised 822 EDTA peripheral blood
      samples from 96 solid organ and 119 bone marrow transplant patients. One sample
      from each of 21 healthy bone marrow donors and 25 blood donors were used as
      controls. Two million leucocytes were lysed and one-tenth of a volume was used in
      a nested PCR employing immediate early gene primers. RESULTS: The limit of
      detection was approximately 10 gene copies of a CMV DNA clone and 1 TCID(50) of
      extracted DNA from a cell suspension. The specificity was >/=0.99 when tested in
      CMV seronegative individuals. The positive and negative predictive values were
      0.62 and 1.00, respectively. When PCR was compared to virus isolation/rapid
      culture in individual patients, PCR was positive more frequently in solid organ
      transplant patients than was CMV isolation/rapid culture, but the difference was
      not significant in bone marrow transplant patients. In isolation-positive
      patients, PCR became positive in samples taken 1-2 weeks earlier. In 54 solid
      organ transplant patients with PCR-positive samples, CMV-associated symptoms were
      present in 29/31 patients with CMV isolated from blood but in only 5/23 patients
      without viraemia. In 17 bone marrow transplant patients treated with ganciclovir,
      PCR became negative during or immediately after treatment in 14/20 (70%)
      episodes. This was true of 5/12 (42%) solid organ transplant patients.
      CONCLUSION: Screening of transplant patients with CMV PCR can be standardized at
      a clinically relevant level so that antiviral therapy can be instituted early.

PMID- 15566797
TI  - Utilization of a DNA enzyme immunoassay for the detection of proviral DNA of
      human immunodeficiency virus type 1 by polymerase chain reaction.
AB  - BACKGROUND: The detection of proviral DNA by Polymerase Chain Reaction (PCR) is
      regarded as an important tool in the diagnosis of HIV-1 infection, specially
      among adults at risk of AIDS and children born to seropositive mothers. However,
      application of PCR in routine testing is hampered by the need to use radioactive
      probes. OBJECTIVES: In this study, a non-radioactive test based on a microtiter
      plate (DNA Enzyme ImmunoAssay, DEIA) was used for the detection of proviral
      sequences of HIV-1 in peripheral blood cells of different patients. The results
      of the PCR-DEIA assay were compared to those obtained by liquid hybridization
      (PCR-LH), virus isolation (VI) and Western blot (WB). STUDY DESIGN: The study
      population included 92 patients belonging to three different groups: seropositive
      subjects with a well-defined clinical status and WB profile; adults at risk of
      infection with negative or indeterminate WB; children born to seropositive
      mothers with still unestablished HIV-1 infection. RESULTS: In the seropositive
      subjects, both PCR-LH and PCR-DEIA confirmed infection and gave the same results
      as WB. In adults at risk of infection, PCR with both methods anticipated the
      seroconversion in one patient with indeterminate WB and confirmed the absence of
      infection among seronegative and other indeterminate patients. In children born
      to seropositive mothers, both PCR systems as well as VI permitted an early
      diagnosis of infection, as confirmed by the clinical follow-up. CONCLUSION: This
      study has shown that in subjects at risk of AIDS and in children born to
      seropositive mothers, the non-isotopic DEIA method presents the same sensitivity
      and specificity for the detection of HIV-1 infection as the radioactive
      procedure. The DEIA method appears to be particularly useful for the detection of
      PCR products in routine diagnostic analyses.

PMID- 15566798
TI  - Diagnosing dengue virus infection in archived autopsy tissues by means of the in
      situ PCR method: a case report.
AB  - BACKGROUND: The pathogenesis of the severe form of dengue virus infection, dengue
      hemorrhagic fever, is still obscure. A major research objective has been to
      determine which body organs are being damaged by dengue virus in this form of
      dengue. Research has been difficult because dengue hemorrhagic fever is sporadic
      and tends to occur in parts of the world where modern facilities are scarce and
      fresh or frozen patient materials are not available. However, major hospitals in
      these areas have accumulated libraries of paraffin-embedded surgical and autopsy
      tissues over the years. These tissues may have been subjected to less than
      optimal fixation and storage. Attempts to localize dengue virus using antigen
      detection in the stored tissue have encountered many difficulties. OBJECTIVE:
      Since viral nucleic acid may be preserved under circumstances which destroy
      protein antigens, our objective was to detect dengue viral RNA in situ in
      histologic sections of tissues from patients dying of dengue hemorrhagic fever in
      Thailand. STUDY DESIGN: Tissues from an 11-year-old boy who died at Ramathibodi
      Hospital, Bangkok, Thailand in November, 1987 with the clinical diagnosis of
      dengue hemorrhagic fever were treated by transcribing the dengue viral RNA to DNA
      followed by amplification using the polymerase chain reaction with subsequent in
      situ hybridization in order to visualize the cells infected with dengue virus.
      RESULTS: Viral RNA was detected in hepatocytes in the mid-zonal region of the
      liver, as well as scattered macrophages in skin and lymph nodes. CONCLUSION:
      Dengue virus infection can be detected in paraffin-embedded autopsy tissues which
      have been stored for five years. The same procedure can be used for diagnosing
      dengue viral infection and for studying the pathogenesis of dengue hemorrhagic
      fever.

PMID- 15566799
TI  - Investigation of a hepatitis A outbreak in a primary school by sequential saliva
      sampling.
AB  - BACKGROUND: An outbreak of hepatitis A occurred in a primary school (children
      aged 4-11 years), starting in the Autumn of 1990 and terminating some 5 months
      later after some spread into the local community. OBJECTIVES: The objectives were
      to monitor the spread of the virus within the primary school over time, to
      document infection in asymptomatic individuals and the efficacy of using saliva
      for HAV antibody detection in young children as an acceptable screening method by
      using the Salivette method and ordinary cotton tipped swabs. STUDY DESIGN: Serial
      saliva samples were taken over a period of months and anti-HAV IgM and IgG
      antibodies measured by radioimmunoassay. RESULTS: Twenty-seven children in the
      school and nine individuals from the surrounding community acquired hepatitis A.
      Twenty-one (78%) of the 27 children were symptomatic, as were all the affected
      adults. The cotton-tipped swabs were found to be as effective a method as
      Salivette at diagnosing infection in those in whom the methods were compared.
      CONCLUSIONS: Despite many reports stating that children are more likely to be
      asymptomatic with HAV infection we found the majority to report significant
      symptoms. Young children do not easily accept serum sampling as a method for
      diagnosis or epidemiological studies, and we show that saliva sampling is an
      effective and acceptable diagnostic method.

PMID- 15566800
TI  - Development of an IgM capture assay for the diagnosis of B19 parvovirus infection
      using recombinant baculoviruses expressing VP1 or VP2 antigens.
AB  - BACKGROUND: The clinical manifestations of human parvovirus B19 infection are
      often similar to those induced as the result of infection by other infectious
      agents such as rubella and some bacteria. Although diagnosis of B19 infection is
      feasible by detection of specific antibodies, the tests require viraemic serum as
      a source of antigen. This inevitably leads to problems of reproducibility and
      dependence upon appropriate high quality clinical material. OBJECTIVES: To
      develop a monoclonal antibody capture ELISA (MACEIA) for detecting anti-B19 IgM
      antibody in human sera, using recombinant baculoviruses expressing the B19
      parvovirus VP1 and VP2 proteins and to compare this with MACEIA using a plasma
      derived B19 antigen. STUDY DESIGN: Sera from 85 patients with proven B19
      infection and the paired convalescent sera from 26 anti-B19 IgM-positive acute
      samples were examined for B19-specific IgM antibody by a monoclonal antibody
      capture assay that utilised recombinant baculoviruses expressing B19 proteins in
      lieu of a plasma-derived B19 antigen. Control samples consisted of 24 anti
      rubella IgM, 24 anti-EBV IgM and 102 negative sera from uninfected individuals.
      RESULTS: Eighty-four of the 85 sera were anti-B19 IgM positive by MACEIA using
      recombinant baculovirus derived B19 antigen and by indirect immunofluorescence
      tests, whereas 79 were positive by MACEIA using plasma-derived antigen. Of the 26
      convalescent samples which were positive as acute sera, 4 had become negative by
      8 weeks post-infection. The expressed recombinant baculovirus antigens had
      identical molecular weights to the VP1 (84 kDa) and VP2 (58 kDa) proteins of
      virus purified from human plasma. Recombinant baculovirus-derived VP1 antigen was
      as effective as VP2 particles at detecting antibodies. CONCLUSIONS: Recombinant
      proteins VP1 and VP2, obtained from recombinant baculovirus-infected cell lysate,
      showed equal specificity to and higher sensitivity than, B19 virus purified from
      human plasma when used in MACEIA to detect B19-IgM antibody.

PMID- 15566801
TI  - An evaluation of a hemagglutination-inhibition test for the detection of
      antibodies to herpes simplex virus type 1.
AB  - BACKGROUND: We have recently demonstrated the ability of herpes simplex virus
      type 1 (HSV-1) to agglutinate mouse red blood cells, and identified glycoprotein
      C (gC-1) as a major virus hemagglutinin. Based on this a classical
      hemagglutination-inhibition (HI) assay was developed. OBJECTIVES: Regarding
      significant structural differences between HSV-1 gC-1 and its herpes simplex
      virus type 2 (HSV-2) counterpart, gC-2, the possibility of application of a
      classical HI assay for the detection of HSV-1-specific antibodies was explored.
      STUDY DESIGN: HI antibody titers were compared with those of gC-1-specific enzyme
      linked immunoassay (ELISA), and with the results of the standard gG-1- and gG-2
      specific immunodot enzymatic assays for the detection of type-specific antibodies
      to HSV-1 and HSV-2 respectively. RESULTS: The sensitivity of HI test was 89% and
      97% of that gC-1-ELISA and gG-1-immunodot respectively. Approximately 21% of
      serum specimens, defined as containing antibodies specific for only HSV-2, showed
      low HI titers. Heterotypic reactivity with purified gC-1 antigen was also
      observed in both ELISA and immunoblot assays. CONCLUSION: Antibodies detectable
      in HI assay were mainly HSV-1-specific; however, a limited degree of serologic
      reactivity between HSV-2-specific sera and HSV-1 hemagglutinin also occurred.
      Thus, our results confirmed prevalent opinion about the presence of a limited
      number of antigenic determinants shared by HSV-1 gC-1 and HSV-2 gC-2.

PMID- 15566802
TI  - Evaluation of the automated vitek immunodiagnostic assay system (VIDAS) for the
      detection of measles (rubeola) IgG antibodies.
AB  - BACKGROUND: The VIDAS MSG assay is a rapid, automated assay system for the
      detection of measles antibodies which has not yet been fully evaluated.
      OBJECTIVES: To compare the VIDAS MSG assay with hemagglutination inhibition (HAI)
      and a commercial enzyme immunoassay (EIA) for the determination of measles immune
      status. STUDY DESIGN: Four hundred and seventy-seven serum samples collected from
      hospital employees for pre-employment screening were tested for measles
      antibodies using the VIDAS MSG assay and the results compared with those obtained
      by HAI and EIA. Intra-and inter-assay precision runs of the VIDAS instrument were
      evaluated using the positive standard provided by the manufacturer. RESULTS: The
      sensitivity of the VIDAS assay compared to HAI and EIA was 96.4% and 96.7%,
      respectively. The specificity of the VIDAS assay, when grouping equivocal with
      negative results was 77.6% and 100% compared to HAI and EIA respectively. The co
      efficient of variation for both precision runs was less than 10%, indicating good
      reproducibility. CONCLUSIONS: The VIDAS MSG assay system is rapid and less labour
      intensive than HAI and manual EIA for the detection of measles antibody. The
      significance of equivocal results is not known, but may represent low, non
      protective antibody levels. Testing of equivocal samples using another test may
      provide a definitive (positive or negative) result, but the degree of protection
      afforded by a positive result is not known. Alternatively, equivocals may be
      grouped with negatives for exposure or vaccination purposes. This may result in
      overuse of vaccine if the VIDAS MSG assay is used to determine immune status in
      screening programs such as pre-employment of hospital staff.

PMID- 15566803
TI  - Diagnosis of astrovirus by reverse transcriptase PCR in stools from patients in
      the UK and Saudi Arabia.
AB  - BACKGROUND: Astroviruses are becoming increasingly recognised as a cause of
      diarrhoea in children, and to a lesser extent, adults. Electron microscopy is the
      recognised standard for diagnosis but is not available in many centres.
      OBJECTIVES: This study set out to evaluate a RT-PCR method for the diagnosis of
      astrovirus in faecal specimens. STUDY DESIGN: 130 diarrhoeal stools were
      collected prospectively both from Saudi Arabia and Leicester, UK. The patients
      from each centre were age-matched. Twenty control isolates from food service
      staff without clinical illness were also collected. Both electron microscopy (EM)
      and RT-PCR (for astrovirus serotype 1) were used to diagnose astrovirus
      infection. RESULTS: Of 23 PCR-positive specimens, only 17 were detected by EM.
      The prevalence of astrovirus serotype 1 was determined by PCR as 1.5% in Saudi
      Arabia and 4.6% in the UK. CONCLUSION: RT-PCR is a more sensitive alternative to
      EM for astrovirus serotype 1.

PMID- 15566804
TI  - Monoclonal antibodies to p24-core protein of HIV-1 mediate ADCC and inhibit virus
      spread in vitro.
AB  - BACKGROUND: Certain antigens of the HIV-1, e.g., gp120-envelop proteins, can be
      expressed on the membrane of HIV-infected cells. Little is known about the
      membrane expression of other HIV-antigens and their interaction with specific
      antibodies. OBJECTIVE: To develop murine monoclonal antibodies (mAbs) to the p24
      core protein of HIV-1 and to characterise their binding sites and biological
      activities on HIV-infected T cells. METHODS: Monoclonal antibodies were developed
      from mice hyperimmunised with a recombinant p24-core protein from HIV-1. Two mAbs
      were epitope-mapped on overlapping peptides and characterised for their
      reactivity with non-fixed HIV-infected T cells by immunofluorescence staining and
      flow cytometric analysis. Their biological activities were studied for antibody
      dependent cellular cytotoxicity (ADCC) and suppression of viral spread in vitro.
      RESULTS: The epitopes of two selected mAbs were located on the amino terminal
      region of p24 in the regions 147-152 aa and 178-187 aa, respectively. The
      antibodies were able to react with living HIV-1 infected cells. The expression of
      the antigens was time-dependent after the infection of certain cell lines by HIV
      1. The mAbs mediated a strong HIV-1-specific ADCC and were able to delay the
      spread of HIV-1 for about 6 days in cell cultures. CONCLUSIONS: Certain epitopes
      of the p24-core protein of HIV-1 can be expressed on living, HIV-infected T cells
      and are recognised by specific antibodies. Such antibodies can destroy infected
      cells by ADCC or delay the virus spread, and therefore, should be considered in
      immunisation strategies against HIV.

PMID- 15566805
TI  - Detection of Coxsackievirus B3 RNA in mouse myocarditis by nested polymerase
      chain reaction.
AB  - BACKGROUND: A majority of cases of viral myocarditis are associated with group B
      Coxsackieviruses (CVB) and the persistence of these viruses in the myocardium is
      associated with the progression of acute myocarditis to chronic dilated
      cardiomyopathy. A highly sensitive nested polymerase chain reaction (NPCR) is
      required to study the mechanisms of viral persistence in the myocardium.
      OBJECTIVES: To develop an enterovirus group-specific NPCR system, to compare it
      to the reverse-transcription PCR (RT-PCR) plus Southern hybridisation and to
      investigate the dynamics of viral RNA in a murine model of myocarditis induced by
      CVB3. STUDY DESIGN: Primers corresponding to the conserved sequences in the 5'
      nontranslated region of enteroviruses were designed to ensure a broad
      specificity. The specificity of PCR products was confirmed by Southern
      hybridisation. The sensitivity of RT-PCR or NPCR was assessed using reconstructed
      infected muscle samples. The myocardial samples of the SWR murine model of CVB3
      myocarditis were collected from day 1 to 30 after infection. The presence of
      viral RNA was detected by the RT-PCR or NPCR and infectious virus was isolated by
      cell culture. RESULTS: Both RT-PCR and NPCR could detect all 11 representative
      enteroviruses. The NPCR could detect as few as 0.01 plaque forming unit of virus,
      100 times more sensitive than the RT-PCR. Virus was isolated from the myocardium
      in acute phase, but was no longer recoverable after 9 days. Viral RNA was
      detected by the NPCR technique throughout the studied period. CONCLUSIONS: An
      enterovirus group-specific NPCR system was developed and was much more sensitive
      than the RT-PCR technique. It can replace the Southern hybridisation of RT-PCR
      products. The presence of viral RNA in the myocardium after acute phase indicates
      a possibility of CVB3 shifting to persistent infection in the SWR mice.

PMID- 15566806
TI  - Direct and uninterrupted RNA amplification of enteroviruses with colorimetric
      microwell detection.
AB  - BACKGROUND: Enteroviruses (EV) cause a broad spectrum of human diseases, of which
      aseptic meningitis is among the most common and most clinically vexing. While the
      clinical symptoms of meningitis caused by bacteria, fungi and viruses are
      similar, the diagnosis, therapy and outcome of disease caused by these agents
      vary greatly. In order to appropriately manage meningitis patients, rapid and
      reliable diagnosis of EV meningitis impacts significantly on patient management.
      OBJECTIVE: To develop a direct and uninterrupted RNA amplification of
      enteroviruses using rTth DNA polymerase. STUDY DESIGN: Purified coxsackievirus B6
      RNA of various concentrations was amplified by rTth DNA polymerase-mediated
      amplification to determine analytic sensitivity. The specificity of the EV
      amplification was examined with a panel of nucleic acids from 36 EV serotypes, 15
      non-EV pathogens and 10 coded clinical specimens of cerebrospinal fluid (CSF).
      RESULTS: All EV serotypes tested were detected successfully by this method at a
      sensitivity of 1 TCID(50) with the exception of echoviruses 1, 5, 22 and 23.
      Echovirus 5 was detected at 10 TCID(50), and echovirus 1 was detected at 100
      TCID(50). Echoviruses 22 and 23 were not detectable at 100 TCID(50). Cross
      reactivity of EV RT-PCR assay with 15 known non-EV meningitis pathogens has not
      been observed. Results of 10 CSF tested with this system correlated well with
      tissue culture. CONCLUSIONS: We have developed an EV amplification assay which
      has several important advantages over previously reported methods. This assay
      employs rTth DNA polymerase which possesses both reverse transcriptase and DNA
      polymerase activities, simplifying RNA reverse transcription and DNA
      amplification to an uninterrupted reaction. Additionally, potential carryover
      contamination and enhanced amplification specificity is provided by substituting
      dUTP for dTTP and adding uracil N-glycosylase (UNG) in the amplification
      reaction. Finally, the detection of amplified product is via a colorimetric,
      microwell format permitting the use of readily available instrumentation.

PMID- 15566807
TI  - A rapid, direct test for zidovudine susceptibility in clinical isolates of human
      immunodeficiency virus type 1 (HIV-1) from infected children.
AB  - BACKGROUND: Existing phenotypic tests of antiretroviral susceptibility in
      clinical isolates of human immunodeficiency virus (HIV) are expensive and slow,
      and require passage of virus in cell culture with the possible consequence of
      selecting variants. OBJECTIVES: We sought to develop a rapid 14-day assay for
      zidovudine susceptibility of cell-associated HIV performed directly in patient
      blood samples. STUDY DESIGN: Twenty-three tests were performed prospectively in
      21 children, and the results were compared with those of the AIDS Clinical Trials
      Group/Department of Defense consensus drug susceptibility assay (DSA) as well as
      certain clinical parameters. RESULTS: Five strains from ZDV-naive children were
      sensitive by the rapid test. Three were tested by DSA, and all were sensitive.
      Six strains from children who had received >/=24 months of ZDV were resistant by
      the rapid assay. Four of these strains were tested by the DSA, and all were shown
      resistant. The viral strains from children who received <24 months of therapy or
      who had switched from ZDV to other antiviral therapy exhibited variable
      sensitivity by both tests. Changes in CD4 cells in the subsequent 6 months, as
      well as weight gain during this time were both correlated to the results of the
      rapid test. The syncytium-inducing capacity of the virus strains was analyzed
      similarly. CONCLUSIONS: The rapid intracellular virus susceptibility assay is a
      test of drug sensitivity performed on HIV growing in cells obtained directly from
      an infected patient. The test has a two-week turn-around time and, in this
      preliminary report, gives results which correlate with both time on zidovudine
      and also subsequent CD4 cell changes.

PMID- 15566808
TI  - Acute symptoms and sequelae of Ross River virus infection in South-Western
      Australia: a follow-up study.
AB  - BACKGROUND: Unusually high tides along the south-west coast of Western Australia
      (WA) during the spring and summer of 1988-89 provided ideal breeding conditions
      for mosquito vectors of Ross River virus (RRV). This was followed by the biggest
      outbreak of RRV infection ever documented in WA (330 notified cases). OBJECTIVES:
      To describe the nature and duration of symptoms of RRV infection in WA, and
      associated functional disability; to determine the perceived effectiveness of
      treatments; to determine the usefulness of available information on RRV
      infection. STUDY DESIGN: A retrospective study of all cases of RRV infection
      reported from South West WA during the 1988-89 outbreak, using a self
      administered patient questionnaire. RESULTS: The most common symptoms were
      arthralgia, tiredness and lethargy, and joint stiffness and swelling. In patients
      with joint manifestations, the knees, wrists and ankles were almost always
      affected. Non-steroidal anti-inflammatory agents, rest, simple analgesics and
      hydrotherapy were subjectively the most helpful treatments. Only 27% of patients
      had recovered completely within 6 months of onset of symptoms. Three years after
      the outbreak, up to 57% still experienced at least intermittent joint symptoms.
      Less than one-third of people reported that the available information adequately
      explained the consequences of RRV infection. CONCLUSIONS: Compared with patients
      elsewhere in Australia, people infected with RRV in the South West of WA
      experience a slightly different spectrum of clinical symptoms, with a longer
      period of disability. This may be related to the presence of a different topotype
      of the virus to that found elsewhere in Australia. Better information for doctors
      and patients on the likely course of the illness is needed. Future studies should
      examine the economic cost associated with RRV infection, and evaluate treatments
      to shorten the period of disability.

PMID- 15566809
TI  - Prevalence and distribution of BK virus subtypes in healthy people and
      immunocompromised patients detected by PCR-restriction enzyme analysis.
AB  - BACKGROUND: Four antigenic subtypes of BK virus (BKV) have recently been
      characterised by both genomic subtyping and serological reactivity. OBJECTIVES:
      To study the prevalence and distribution of subtypes of BKV in different groups
      of patients. STUDY DESIGN: Urine specimens were collected from 33 bone marrow
      transplant (BMT) recipients, from 101 HIV-infected patients, from 15 children
      aged 2-5 and from 40 pregnant women were tested for BKV DNA by polymerase chain
      reaction (PCR) and subtyped using a PCR-sequencing (PCR-S) and a modified PCR
      restriction enzyme analysis (PCR-RE) methods. RESULTS: BKV DNA was detected in
      12/18 (67%) of BMT patients with haematuria and 5/15 (33%) without. Overall BKV
      DNA was detected in 45% of HIV-infected patients, the prevalence of BKV DNA
      increased with greater immunosuppression as defined by CD4 cell counts. BKV DNA
      was detected in urine samples from 27% of children and 47% of pregnant women.
      Four stable BKV subtypes were detected in these patient groups. Dual infections
      with more than one subtype were identified in urine samples from HIV-infected
      patients, children and pregnant women but not in the samples from bone marrow
      recipients. CONCLUSION: This study has confirmed the high prevalence of BKV
      infection in immunocompromised patients and suggests that stable BKV subtypes
      with conserved sequences are circulating in the human population. The techniques
      of PCR-S and PCR-RE described in this study are sufficiently sensitive for
      subtyping BKV direct from clinical specimens.

PMID- 15566810
TI  - Prevalence of antibody to human herpesvirus 7 in children in Japan.

PMID- 15566811
TI  - HIV-1 chemotherapy and drug resistance.
AB  - BACKGROUND: Therapy with inhibitors of human immunodeficiency virus type 1 (HIV
      1) replication has had only transient clinical benefit to date. It has been
      speculated that drug-resistant virus mutants may contribute to therapeutic
      failure. OBJECTIVE: To extrapolate from the biology of drug-resistant HIV-1 to
      improve antiretroviral chemotherapeutic strategies. STUDY DESIGN: The literature
      was reviewed in regard to clinical and virologic correlates of HIV-1 drug
      resistance, methodology for detection of resistant virus, and chemotherapeutic
      strategies for prolonging suppression of virus replication. RESULTS: HIV-1
      isolates resistant to different nucleoside reverse transcriptase (RT) inhibitors,
      nonnucleoside RT inhibitors, and protease inhibitors have been implicated to
      different extents with virologic or clinical failure of therapeutic
      effectiveness. The in vivo antiviral effect of certain nonnucleoside RT
      inhibitors as monotherapy is lost coincident with emergence of a dominant
      population of resistant virus. Disease progression is more rapid among patients
      at advanced stages of HIV-1 disease with highly zidovudine (AZT)-resistant virus
      (50% inhibitory concentration 1.0 muM AZT) and is not attributable to effects of
      other baseline predictors of progression studied to date. However, there is no
      definitive evidence that high level AZT resistance causes the loss of therapeutic
      benefit of AZT. Several of the research methods used for detection of drug
      resistant mutants could be developed for future use as screening assays in
      clinical virology laboratories. CONCLUSIONS: Strategies for individualizing
      therapy based on switching, or adding, drugs at first detection of drug-resistant
      HIV-1 aim to minimize replication of viruses that are drug-resistant, as well as
      those that remain susceptible to the drug. If clinical investigation reveals that
      such approaches extend duration of antiretroviral therapeutic benefit, HIV-1 drug
      resistance assessment may be increasingly requested from clinical virology
      laboratories. Monitoring antiviral suppression by quantifying plasma HIV-1 RNA
      appears more practical at present, however. Different combination regimens are
      also being studied to see if some regimens delay emergence of resistant virus
      longer than others. In the future, sequential empiric changes to new combination
      regimens every few months may also bear investigation to attempt to "pre-empt"
      HIV-1 resistance development.

PMID- 15566812
TI  - Direct quantitative comparison of shell vial and conventional culture for
      detection of CMV viremia.
AB  - BACKGROUND: Centrifugation shell vial (SV) and conventional tube culture (TC) are
      the most common methods for detecting cytomegalovirus (CMV) viremia. Studies have
      indicated that SV is more sensitive than TC but at least one report suggested
      that TC was more sensitive. Because CMV in the blood is primarily associated with
      infected leukocytes, the number of leukocytes inoculated into the different
      culture systems could affect the sensitivities of the two systems. OBJECTIVES: To
      compare the sensitivities of SV and TC for detection of CMV viremia by
      inoculating equal numbers of leukocytes into paired SV cultures and TC cultures.
      STUDY DESIGN: Leukocytes from transplant recipients were isolated and counted.
      Equal numbers of leukocytes were then inoculated into each of two MRC-5 SV and
      into each of two MRC-5 TC. SV was considered positive when either one or both
      vials were positive, and TC was considered positive when either one or both tubes
      showed evidence of CMV cytopathic effect (CPE). RESULTS: From a total of 434
      specimens tested, 85 (19.6%) were positive by SV or TC. CMV was detected by SV in
      75 (88%) of the positive specimens, compared to TC which was positive in 40 (47%)
      of the positive specimens. CONCLUSIONS: When equal numbers of leukocytes were
      inoculated into each system, SV had significantly greater sensitivity than TC for
      detecting CMV viremia. However, a small number of episodes of viremia were
      detected only by TC. Therefore, both methods should be used for maximum
      sensitivity.

PMID- 15566813
TI  - Application of fluoroimmunoassay to the identification of low avidity specific
      IgG against pathogenic human viruses and Toxoplasma gondii.
AB  - BACKGROUND: Serological diagnosis of primary viral infections is usually made by
      detection of specific IgM. In some cases, false positive results (mainly due to
      crossreactions between closely related viruses) can be obtained. Moreover, some
      primary infections occur without specific IgM response. Thus, alternative
      serological approaches are required for diagnosis. Detection of low avidity,
      specific IgG has been applied as a useful serological marker for diagnosing
      infections caused by several viruses and Toxoplasma gondii. OBJECTIVE: The
      standardization and application of specific IgG avidity assays using a
      semiautomated solid phase immunoassay (fluoroimmunoassay (FIA)) on the basis of
      the urea elution principle, for the characterization of low avidity specific IgG
      against rubella virus, herpes simplex virus (HSV), varicella-zoster virus (VZV),
      cytomegalovirus (CMV) and T. gondii. STUDY DESIGN: The method consists of two
      simultaneous determinations, one as recommended by the manufacturer and the other
      including a washing step with 8 M urea after the antigen-antibody reaction. A
      reduction in titer higher than, or equal to, 50% was considered indicative for
      presence of low avidity specific IgG. RESULTS: When applied to the diagnosis of
      infections, this method showed sensitivity ranging from 81% to 100%, and absolute
      specificity. The detection of low avidity specific IgG allowed the
      differentiation between primary and recurrent infections caused by VZV.
      Furthermore, it helped in the identification of CMV as the etiological agent of
      congenital infection in the absence of specific IgM response, as well as in the
      elucidation of crossreactivity between antigenically related viruses, i.e., VZV
      and HSV, and Epstein-Barr virus and CMV. CONCLUSION: FIA can be used for the
      characterization of the avidity of specific IgG antibody as a diagnostic test in
      clinical laboratories.

PMID- 15566814
TI  - Diagnosis of human herpesvirus-6 infection in two patients with central nervous
      system complications.
AB  - BACKGROUND: Although exanthem subitum (ES) is generally a mild, self-limiting
      disease of early childhood, some cases of ES are complicated by seizures and
      encephalopathy. The presence of human herpesvirus-6 (HHV-6) DNA in cerebrospinal
      fluid (CSF) of these patients suggests that HHV-6 can infect the central nervous
      system (CNS) causing encephalitis. OBJECTIVES: To demonstrate HHV-6 infection in
      two patients with serious CNS complications. The patients, a child and an adult,
      failed to develop the characteristic rash normally associated with ES. STUDY
      DESIGN: Peripheral blood mononuclear cells (PBMCs) and CSF were examined for the
      presence of HHV-6 or viral DNA, using virus isolation techniques and the
      polymerase chain reaction (PCR). Serum samples were tested by immunofluorescence
      (IF) and enzyme linked immuno-sorbent assay (ELISA) for the presence of anti-HHV
      6 IgM and anti-HHV-6 IgG respectively. RESULTS: HHV-6 was isolated from the PBMCs
      of the adult patient and the presence of virus in these cells was confirmed using
      electron microscopy. HHV-6 DNA was detected in CSF taken early during the
      infection in both patients, together with anti-HHV-6 IgM antibodies and
      increasing levels of anti-HHV-6 IgG. CONCLUSIONS: The diagnosis of HHV-6
      infection in these patients was confirmed either by virus isolation or by the
      detection of HHV-6 DNA in the CSF, and the results of serology. These cases show
      that HHV-6 infection may result in serious CNS complications, in children and
      adults.

PMID- 15566815
TI  - A nitrocellulose membrane based IgM capture enzyme immunoassay for etiological
      diagnosis of dengue virus infections.
AB  - A nitrocellulose membrane based immunoassay for the detection of dengue virus
      specific IgM suitable for use in field situations or in peripheral laboratories
      would be useful for disease surveillance and control. This paper describes such
      an assay in an IgM capture format (MAC DOT) similar to the microplate based MAC
      ELISAs currently in use in several research and reference laboratories around the
      world. The MAC DOT was tested on several sample sets including a retrospective
      study of 119 patients from Children's Hospital, Bangkok, Thailand, with confirmed
      dengue infection. The sensitivity of the test was shown to be 94% taking only
      admission sera into consideration but rising to 99% when both an admission and a
      discharge specimen were considered. Other sample sets confirmed the high
      sensitivity and a study of 494 unselected febrile children showed that the
      specificity of the MAC DOT was 98%.

PMID- 15566816
TI  - Comparison of monoclonal biotin-avidin enzyme immunoassay and monoclonal time
      resolved fluoroimmunoassay in detection of respiratory virus antigens.
AB  - BACKGROUND: Detection of respiratory viruses by time-resolved fluoroimmunoassay
      based on monoclonal antibodies were developed in our laboratories in the late
      1980s and they have been successfully used in daily diagnosis for more than seven
      years. Later, similar Biotin-EIAs were developed but the sensitivities were
      unsatisfactory. OBJECTIVES: Further optimization of monoclonal Biotin-EIAs and
      comparison of the optimized assays with TR-FIAs. STUDY DESIGN: Variations in test
      format, diluents, incubation times and temperatures, and different monoclonal
      antibodies were tested, and the final comparisons were made with TR-FIA using
      stored nasopharyngeal aspirates. RESULTS: The improvements in Biotin-EIA featured
      four changes which increased sensitivity in the assay: (a) test diluent contained
      diethylenetriamino-pentaacetic acid; (b) antigen and biotinylated detector
      antibody were added simultaneously; (c) reaction time was extended from 1 h at 37
      degrees C to overnight at 4 degrees C; (d) from the thirteen monoclonal
      antibodies used in TR-FIA, ten were optimal also in Biotin-EIA, but in the
      parainfluenza 1 and 2 assays other monoclonals proved more sensitive. Out of 257
      originally positive specimens tested in the comparison studies, 192 (74.7%) were
      again positive and 54 (21.0%) were negative in both assays; nine were negative in
      TR-FIA but positive in Biotin-EIA, while two specimens were negative in Biotin
      EIA but positive in TR-FIA. The overall agreement between the two assays was
      95.7%. CONCLUSIONS: All monoclonal Biotin-EIAs can be optimized to the same
      sensitivity as TR-FIAs for the detection of respiratory viruses. Laboratories
      which have no TR-FIA expertise may use Biotin-EIA in the diagnosis of acute
      respiratory infections.

PMID- 15566817
TI  - Monoclonal antibodies for the direct detection of influenza-A virus by ELISA in
      clinical specimens from patients with respiratory infections.
AB  - BACKGROUND: Monoclonal antibody technology provides antibody reagents of known
      specificity, high titres and unlimited availability, that form ideal reference
      antibodies for use in specific viral antigen-detection methods. OBJECTIVES: To
      produce mouse monoclonal antibodies against antigenic sites of influenza-A virus,
      and evaluate their use as diagnostic reagents in a sandwich ELISA. STUDY DESIGN:
      (1) Production and characterization of monoclonal antibodies against influenza-A
      virus; (2) application of these antibodies in an ELISA method for direct antigen
      detection; and (3) evaluation of the ELISA as routine procedure. RESULTS: Four
      monoclonal antibodies (A1-A4) from mice immunized intranasally with influenza-A
      virus were selected according to their specific reactivity with either
      nucleoprotein or matrix protein antigens as demonstrated by Western blot
      analysis. These antibodies lacked haemagglutination inhibition and neutralization
      properties and recognized both H1N1 and H3N2 strains of influenza-A virus
      equally. A sandwich ELISA using unlabelled antibodies for antigen capture and
      biotin-labelled antibodies for antigen detection was used to analyse
      nasopharyngeal secretions or nasal swabs from culture-confirmed influenza-A
      infected patients and comparable specimens from patients with other viral
      respiratory infections. Only influenza-A virus (strains H1N1 and H3N2) could be
      detected in samples from patients with known influenza-A and influenza-B
      infections, and also after re-isolation of such viruses in conventional cultures
      of MDCK cells or embryonated hens' eggs. The antigen-detection assay showed a
      diagnostic sensitivity of 100% and a specificity of 98.3% compared with
      conventional culture methods. CONCLUSION: The reported ELISA appears to be a
      rapid and inexpensive method for diagnosis and epidemiological studies of
      influenza-A infections.

PMID- 15566818
TI  - Continuous detection of CMV DNA in plasma of patients with advanced HIV infection
      implies the poorest prognosis.
AB  - BACKGROUND: The contribution of cytomegalovirus (CMV) to progressive HIV
      infection is still controversial. OBJECTIVE: The occurrence of CMV DNA in the
      plasma of patients with advanced HIV infection was studied in relation to the
      development of clinical disease. STUDY DESIGN: Plasma samples were collected
      every 2 weeks for 6 months. The patients have thereafter been followed clinically
      at least every 3 months. CMV DNA was extracted and analysed by a nested PCR.
      RESULTS: CMV DNA was repeatedly detected in the plasma of five patients for more
      than 45 days (group 1). These patients also had very low CD4+ cell counts 51+/-41
      x 10(6) /l). Three patients in group 1 developed CMV complications and CMV was
      the cause of death in two cases. Two patients with anti-CMV IgM responses did not
      develop CMV complications. All five patients died at a mean of 17 months after
      CMV DNA became continuously detectable by PCR. In another six patients, CMV DNA
      was not or only sporadically detected (group 2). In these six patients, four are
      still alive after more than 3.5 years and only one patient developed CMV
      retinitis 3 years later. CONCLUSIONS: The presence of CMV DNA in plasma was
      frequent in 11 patients with advanced HIV infection. The continued presence of
      CMV DNA in plasma of the patients with low CD4+ cell counts was related to the
      development of clinical CMV disease and carried the poorest prognosis.

PMID- 15566819
TI  - A pilot, open-labelled, phase II study using oral ribavirin in the treatment of
      patients with chronic active hepatitis B.
AB  - BACKGROUND: Ribavirin is a synthetic purine nucleoside with demonstrated
      antiviral activity against several DNA and RNA viruses. OBJECTIVES: An open
      labelled pilot study to evaluate the safety and effect of ribavirin in the
      treatment of patients with chronic active hepatitis B (CAH-B). STUDY DESIGN: 24
      CAH-B patients were treated with oral ribavirin 1200 mg daily in 3 divided doses
      for 4 weeks. Biochemical and virological parameters were monitored at regular
      interval during and after treatment. RESULTS: The serum hepatitis B e antigen
      (HBeAg) and HBV DNA measured by dot-blot hybridization were positive in all
      patients before treatment. At the end of 4 weeks of therapy, the HBV DNA levels
      decreased in 15 (63%) patients and became undetectable in 1 (4%) of these
      individuals. The mean HBV DNA decreased from 288+/-78 pg/ml at baseline to 219+/
      79 pg/ml at the end of the 4 weeks of treatment (p = 0.046). Eight weeks after
      cessation of treatment, HBV DNA was undetectable in 10 (42%) patients, and the
      mean HBV DNA was 46+/-23 pg/ml (p < 0.01 when compared to mean baseline value).
      Seven (29%) patients seroconverted from HBeAg positive to anti-HBe positive but
      no patients lost hepatitis B surface antigen (HBsAg) during the 8 weeks of follow
      up. At the end of 4 weeks of ribavirin treatment, serum levels of alanine
      aminotransferase (ALT) decreased in all but 1 patient; only 1 patient normalized
      serum ALT at this time. The mean serum ALT decreased significantly from 416+/-72
      IU/l at baseline to 179+/-35 IU/l at the end of 4 weeks of treatment (p = 0.001).
      Eight weeks after cessation of therapy, the mean serum ALT value was 151+/-32
      IU/l (p < 0.001 when compared to mean baseline value) and 5 (21%) patients
      normalized serum ALT at this time. During ribavirin treatment, the main side
      effect was a decrease in the hemoglobin level which returned to the pretreatment
      level in each instance within 2 months after discontinuance of therapy.
      CONCLUSIONS: Results of this pilot study indicated that oral ribavirin was well
      tolerated in CAH-B patients and resulted in lowering of serum ALT and HBV DNA
      values. A randomized controlled trial is needed to fully evaluate the beneficial
      effects of ribavirin in CAH-B patients.

PMID- 15566822
TI  - Mysteries and miracles: personal recollections in clinical and diagnostic
      virology.

PMID- 15566823
TI  - Human herpesvirus-7 (HHV-7): current status.
AB  - BACKGROUND: Human herpesvirus-7 (HHV-7) is a newly discovered virus and very
      little is known about its prevalence, biologic, immunologic and molecular biology
      aspect. Besides the HHV-7 etiologic role in a few cases of exanthem subitum, its
      association with other diseases has not been reported. OBJECTIVES: To review what
      is currently known about HHV-7. RESULTS: HHV-7 was first isolated in 1990 from
      purified T-cells from a healthy individual. Following this report, an independent
      isolation of HHV-7 was reported from the mononuclear cells (PBMC) of a chronic
      fatigue syndrome patient. HHV-7 is closely related to human herpesvirus-6 (HHV-6)
      and human cytomegalovirus (HCMV), but is distinct from Epstein-Barr virus (EBV),
      herpes simplex virus and varicella zoster virus. Using polyvalent and monoclonal
      antibodies, several HHV-7 viral proteins were identified, ranging from 136 to 30
      kDa. HHV-7 infection occurs later than HHV-6, which appears in early childhood.
      HHV-7 is ubiquitous, and its prevalence rate is >85% in the US population,
      although its rates of prevalence in Japan is lower than in the USA and Europe.
      HHV-7 is frequently isolated from saliva; however, HHV-7 has been consistently
      isolated from PBMC from young children as well. Several cases of exanthem subitum
      have been linked to primary infection of HHV-7, suggesting that it may also cause
      exanthem subitum. Primary infection with HHV-7 was also reported from a patient
      with features of hepatitis and exanthem subitum. This virus was also isolated
      from tissues from a case of hepatosplenomegaly and pancytopenia lacking either
      EBV or HCMV. Thus far, no other disease associated with HHV-7 has been reported.
      Only one continuous T-cell line (SupT1) can support the replication of HHV-7, but
      the virus yield is extremely low. CONCLUSIONS: It has been about 4 years since
      this member of the human herpesvirus family was reported. In the coming years,
      more data will be available on the epidemiology, biology, immunology, molecular
      biology, and pathogenesis of HHV-7. The finding of reciprocal interference
      between HHV-7 and HIV-1, suggesting competition at the receptor level is
      important, needs further work and here HHV-7 may play a role as a negative
      cofactor in the natural history of HIV infection. Because of HHV-7 interaction
      with HIV-1, the possibility of its vertical transmission needs to be
      investigated. This review on HHV-7 is intended to provide current information on
      HHV-7.

PMID- 15566824
TI  - Large-scale evaluation of an alternative strategy for confirmation of HIV
      antibodies.
AB  - OBJECTIVE: To retrospectively compare the accuracy of combinations of two enzyme
      linked immunosorbent assays (ELISAs) with a Western blot based strategy for
      identification of human immunodeficiency virus type 1 (HIV-1) seropositivity.
      MATERIALS AND METHODS: 48,977 sera, sent to the National Bacteriological
      Laboratory, Stockholm, Sweden, for HIV antibody determinations between October
      1988 and June 1993, were investigated. All samples were tested in parallel with
      two different ELISAs, either Abbott Recombinant HIV-1 EIA and Wellcozyme
      Recombinant Anti-HIV-1 EIA, or Enzygnost Anti-HIV-1/2 and Wellcozyme Recombinant
      Anti-HIV-1 EIA, or Enzygnost Anti-HIV-1/2 and Wellcozyme Anti-HIV-1+2 EIA. 1565
      sera repeatedly reactive by one or both ELISAs were investigated by Western blot
      (WB). Furthermore, a total of 2820 referred sera, screen reactive at primary
      laboratories but negative on our combinations of two ELISAs were analysed by WB.
      RESULTS: Out of 1244 truly HIV antibody positive samples 1203 were WB positive
      and 41 (3.4%) were WB indeterminate. A sensitivity of 100% was obtained by all
      three combinations of two ELISAs on examination of these 1244 sera including
      repeated testing of 5 samples with initially discrepant results. Among 2820 sera
      from HIV-negative individuals 649 (23%) sera were WB indeterminate. The
      combination of Enzygnost (indirect test with synthetic peptides) and Wellcozyme
      (sandwich test with recombinant and synthetic peptides) Anti-HIV 1+2 EIAs was
      100% specific when used for analysis of 9111 sera. One of 30,323 HIV-1 antibody
      negative sera tested was initially reactive on both Enzygnost Anti-HIV 1+2 and
      Wellcozyme Recombinant Anti-HIV-1 EIA (competitive assay) but was found to be
      negative by repeated testing, resulting in a specificity of 100% for that
      combination of ELISAs. Abbott Recombinant Anti-HIV-1 EIA (indirect assay)
      combined with Wellcozyme Recombinant Anti-HIV-1 EIA was initially falsely
      reactive with 12 of 8272 sera of which 6 were repeatedly reactive. CONCLUSIONS:
      This large-scale evaluation demonstrates that combinations of two ELISAs based on
      different test principles and antigens increase the accuracy of the HIV antibody
      determination and could be used as an alternative or complement to WB.

PMID- 15566825
TI  - Monoclonal antibodies for the rapid diagnosis of influenza-B virus infections by
      ELISA: production and characterization.
AB  - BACKGROUND: Monoclonal antibodies directed against conserved epitopes of viral
      proteins have substantially improved the accuracy of several immunochemical
      methods in diagnostic virology. OBJECTIVES: To characterize mouse monoclonal
      antibodies directed against structural protein antigens of influenza-B virus and
      evaluate their use as diagnostic reagents for the direct detection of such
      antigens in clinical specimens from patients with respiratory infections of
      unknown aetiology. STUDY DESIGN: (a) Production and characterization of
      monoclonal antibodies against influenza-B viral antigens, and (b) their use in
      two different ELISA systems for detecting influenza-B antigen either directly in
      clinical specimens or after confirmation by rapid culture in MDCK cells. RESULTS:
      Four monoclonal antibodies were selected for their specificity for the
      nucleoprotein antigen as demonstrated by Western blot analysis. The specificity
      of these antibodies for different epitopes of the nucleoprotein was demonstrated
      by competition experiments, using unlabelled and biotin-labelled purified
      antibodies in a sandwich assay. All four antibodies belong to the mouse IgG(2a)
      isotype, lack haemagglutination inhibition and neutralization properties and
      exhibit titres as high as 10(-6) in ELISA with as little as 30 ng purified
      influenza-B virus. ELISA methods using these antibodies detected only influenza-B
      viral antigens in direct testing of clinical specimens from patients with known
      influenza-B or influenza-A infections, or after reisolating virus from such
      specimens in tissue culture of MDCK cells. CONCLUSION: The antibodies were
      suitable for the direct detection and typing of influenza-B virus in clinical
      specimens or for use in rapid confirmation cultures.

PMID- 15566826
TI  - Indirect immunofluorescence for serological diagnosis of dengue virus infections
      in Swedish patients.
AB  - BACKGROUND: An increasing number of travellers to dengue endemic areas has
      emphasized the need for an easy and reliable serological test for diagnosis of
      dengue virus infections. OBJECTIVES: Indirect immunofluorescence (IF) and
      hemagglutination inhibition (HI) tests were compared for serological diagnosis of
      dengue fever (DF). STUDY DESIGN: Sera from patients with clinical symptoms
      compatible with DF and a travel history comprising dengue endemic areas were
      included in the study. Paired serum samples from 24 patients and single
      convalescent sera from five patients were investigated by HI and IF. Paired sera
      from ten patients were investigated by plaque reduction neutralization test
      (PRNT) in order to confirm the HI/IF results. RESULTS: In twelve of the patients
      with paired sera a sero-conversion or a significant (4-fold) antibody titer rise
      was seen with HI as well as with IF. Four patients with stationary HI-titers had
      significant titer rises when investigated by IF. Stationary or declining HI- and
      IF-titers were found in the remaining eight patients. The five single sera were
      antibody-positive by both methods. Investigation by PRNT of paired sera from ten
      patients confirmed the IF results. A total of 298 serum samples (paired sera or
      early convalescent samples) were investigated for dengue antibodies by IF. A sero
      conversion, significant titer-rise or an IF-titer of 320 was generally seen 7-13
      days post onset of disease. During the years 1991-1993 altogether 161 cases of
      dengue were diagnosed by IF in Swedish patients, a majority of which had
      travelled to Southeast Asia. CONCLUSION: Antibody detection by indirect IF proved
      to be at least as reliable as HI for diagnosis of dengue infections in Swedish
      patients. The specificity of the IF was ensured by testing the sera of ten
      patients for serotype specific neutralizing dengue antibodies.

PMID- 15566827
TI  - Laboratory acquired tick-borne meningoencephalitis: characterisation of virus
      strains.
AB  - BACKGROUND: The handling of tick-borne encephalitis (TBE) virus is potentially
      hazardous, as indicated by a number of laboratory-acquired infections in the
      prevaccination era. OBJECTIVES: (1) To reemphasize the hazard of handling TBE
      virus without being vaccinated by describing the case of a laboratory-acquired
      full-blown TBE in a microbiologist who isolated the virus from a blood sample.
      (2) To molecularly characterize the causative virus strain isolated in Slovenia
      in comparison with the European prototype strain Neudoerfl. STUDY DESIGN: The
      virological diagnosis of the laboratory infection was established by serology and
      virus isolation. The virus was characterized by restriction fragment analysis of
      PCR products of amplified genomic sequences and a panel of monoclonal antibodies
      reacting with the major envelope protein. RESULTS: The laboratory infection, most
      probably acquired by aerosol, resulted in a biphasic course of the disease with a
      severe meningoencephalitis in the second phase. Both by restriction fragment and
      monoclonal antibody analysis the Slovenian virus strains involved were
      indistinguishable from the European prototype strain. CONCLUSIONS: This report
      confirms the potential hazard of handling TBE virus in the laboratory without
      being vaccinated. The similarity of the virus isolates from Slovenia with the
      European prototype strain confirms the previously observed homogeneity of TBE
      virus strains from different European countries.

PMID- 15566828
TI  - Detection of varicella-zoster virus DNA in maternal breast milk from a mother
      with herpes zoster.
AB  - BACKGROUND: We previously reported that varicella-zoster virus (VZV) DNA was
      detected by polymerase chain reaction (PCR) from maternal breast milk of a post
      partum mother with chickenpox. OBJECTIVES: We tried to decide the route of VZV
      contamination to maternal milk. CASE REPORT: A 22-year-old woman developed herpes
      zoster on her right Th3-4 dermatome. RESULTS AND CONCLUSIONS: VZV DNA was
      detected by PCR from peripheral blood and the maternal milk of the right breast,
      but not from the maternal milk of the left breast. These results suggest that VZV
      in maternal milk may not derive from VZV-infected mononuclear cells in peripheral
      blood, but from the VZV-infected epitheliums of the lacteal gland.

PMID- 15566829
TI  - Evaluation of HIV-1/HIV-2 immunoblots for detection of HIV-2 antibodies.
AB  - OBJECTIVE: To evaluate the sensitivity of commercially available HIV-2
      immunoblots and to identify the HIV-2 glycoproteins on Western blots. METHODS:
      HIV-2 Western blot (WB) strips commercially available from Diagnostic
      Biotechnology, Diagnostic Pasteur and Cambridge Biotech and in-house HIV-2 WB
      strips were investigated by monoclonal HIV-2 gp36 and gp125 antibodies for
      identification of the glycoproteins. The WB strips and commercially available HIV
      1/HIV-2 line immunoassays (LIAs) from Diagnostic Pasteur (PEPTI-LAV 1-2),
      Diagnostic Biotechnology (version 2.2) and Innogenetics (INNO-LIA HIV-1/HIV-2 ab)
      were analyzed by seroconversion panels from HIV-2 infected cynomolgus monkeys
      (Macaca fascicularis) to investigate their sensitivity for detection of HIV-2
      antibodies. The LIAs were also investigated by use of 100 HIV-2 antibody positive
      human sera from Guinea Bissau. The in-house WB strips contained HIV-2/SBL-6669
      antigen treated with various concentrations of sodium dodecyl sulphate (SDS, 0
      2%) at 37 degrees C or 100 degrees C for various times to obtain gp36 in
      oligomeric and/or monomeric form. RESULTS: By use of monoclonal antibodies, WB
      strips from Diagnostic Biotechnology and Diagnostic Pasteur were shown to contain
      gp125 as well as monomeric and oligomeric forms of gp36, whereas Cambridge WB
      strips contained mainly oligomeric gp36 and no detectable gp125. The sensitivity
      of the WB strips for detection of HIV-2 seroconversion was similar if WB
      seropositivity was defined as reactivity with p24 and one envelope protein. When
      the WHO WB criteria were applied requiring reactivity with at least two envelope
      proteins for positivity, the sensitivity of the WB strips from Diagnostic
      Biotechnology and Diagnostic Pasteur was retained, whereas the sensitivity of
      Cambridge Biotech WB strips was reduced. Among 100 HIV-2 antibody positive human
      sera all were reactive on PEPTI-LAV 1-2 and INNO-LIA HIV-1/HIV-2 ab, but two of
      the hundred sera failed to react with the HIV-2 synthetic peptide band on
      Diagnostic Biotechnology version 2.2 WB strips. On in-house WB strips the
      relation between monomeric and oligomeric gp36 was changed by altering the SDS
      concentration and the temperature. Thus the monomeric form increased with the SDS
      concentration and the temperature. The sensitivity for detection of antibodies
      during seroconversion did not differ between the monomeric and oligomeric forms
      of gp36. CONCLUSIONS: The sensitivity for detection of HIV-2 antibodies during
      seroconversion was independent of the oligomeric or monomeric structure of the
      transmembrane glycoprotein. One of the three commercial WB kits tested had a
      lower sensitivity for detection of HIV-2 seroconversion compared with the other
      two kits when the WHO criteria for WB positivity were used.

PMID- 15566830
TI  - A comparative evaluation of three methods of antiviral susceptibility testing of
      clinical herpes simplex virus isolates.
AB  - BACKGROUND: Current methods of antiviral susceptibility testing for herpes
      simplex virus (HSV) are poorly standardized and have rarely been compared
      critically. OBJECTIVES: To compare the three most commonly utilized HSV
      susceptibility assays for accuracy of result, method of implementation, and time
      required. STUDY DESIGN: We compared susceptibility results for acyclovir and
      foscarnet using the plaque reduction, dye uptake and DNA hybridization assays in
      30 patient isolates of HSV, of varying susceptibility pattern. Compared
      parameters included: values for ID(50) (the concentration of drug required to
      inhibit virus growth by 50% or more), ratio of ID(90) to ID(50), and correlation
      of susceptibility result with clinical response to antiviral therapy, when
      available. In addition, we compared ease of the assay, presence of objective
      endpoint, time required to generate the susceptibility result, and necessary
      equipment for implementation. RESULTS: The dye uptake yielded ID(50) results that
      were approximately two-fold greater than those from the plaque reduction assay,
      while ID(50) values from the DNA hybridization assay were one-half those from the
      plaque reduction assay. Comparison of the correlation of susceptibility result
      with clinical response to acyclovir therapy in 17 instances and to foscarnet
      therapy in 10 instances suggested the possibility of a somewhat greater
      discriminative ability of the dye uptake assay, and a somewhat lesser
      discriminative ability of the DNA hybridization assay, when compared with results
      from the plaque reduction assay in isolates with borderline acyclovir
      susceptibility. CONCLUSIONS: Larger comparative studies are necessary to further
      differences in discriminative ability of the three assays for HSV. All three
      assays were deemed suboptimal due to an overly long turnaround time, associated
      expense, and/or level of equipment required for their performance. Continued
      evaluation of alternative, more rapid assays is therefore warranted.

PMID- 15566831
TI  - African green monkey origin of the atypical cytopathic 'stealth virus' isolated
      from a patient with chronic fatigue syndrome.
AB  - BACKGROUND: A cytomegalovirus-like 'stealth virus' had previously been isolated
      from a patient with the chronic fatigue syndrome (CFS). OBJECTIVE: To determine
      the original derivation of this virus. STUDY DESIGN: DNA sequencing of cloned
      regions of the virus was performed and the sequences were compared using BLASTN
      and FASTA analyses against the entire GenBank database. Viral sequences were also
      used to design primers for the polymerase chain reaction (PCR). RESULTS: DNA and
      amino acid sequence comparisons showed that the stealth virus was more closely
      related to the Colburn strain of simian cytomegalovirus (SCMV) than to CMV of
      either human or rhesus monkey origin or to any other sequenced herpesvirus.
      Similarity, but non-identity, between the stealth virus and SCMV, was confirmed
      using PCR. CONCLUSION: The findings implicate the African green monkey as the
      probable source of the virus isolated from this CFS patient.

PMID- 15566832
TI  - Detection of varicella-zoster virus (VZV) DNA in throat swabs and peripheral
      blood mononuclear cells of immunocompromised patients with herpes zoster by
      polymerase chain reaction.
AB  - BACKGROUND: Varicella-zoster virus (VZV) is rarely isolated from throat swabs and
      peripheral blood leukocytes from patients with herpes zoster by conventional
      virus isolation methods. The polymerase chain reaction (PCR) is a highly
      sensitive method to detect VZV genomes. It has been reported that VZV DNA was
      detected in the cerebrospinal fluid (Puchhammerstockl et al., 1991) and
      peripheral blood mononuclear cells (PBMC) of patients with VZV-associated
      neurological symptoms (Gilden et al., 1992) by PCR. OBJECTIVES: We used the
      nested double PCR to detect VZV DNA in patients with herpes zoster. STUDY DESIGN:
      Sixteen patients with herpes zoster, ten immunocompromised and six
      immunocompetent patients, were studied. Throat swabs and PBMC were collected
      weekly and examined for VZV DNA by the nested double PCR. RESULTS: VZV DNA was
      detected in 60% (6/10) of throat swabs and in 60% (6/10) of PBMC of
      immunocompromised patients, and in 16.7% (1/6) of throat swabs and in 33% (2/6)
      of PBMC of immunocompetent patients within two weeks after the onset of skin
      rash. VZV DNA was detected in throat swabs or PBMC of two patients 5 and 7 days
      after cessation of acyclovir. CONCLUSION: VZV DNA was detected in throat swabs
      and PBMC-associated viremia exist in patients with herpes zoster. It is suggested
      that VZV spread from sensory ganglia to the skin or pharyngeal area along the
      nerve fiber or hematogenously and local cutaneous replication of VZV can lead to
      viremia with subsequent hematogenous dissemination in patients with herpes
      zoster.

PMID- 15566833
TI  - Semi-nested PCR using NS3 primers for the detection and typing of dengue viruses
      in clinical serum specimens.
AB  - BACKGROUND: More rapid, specific and sensitive tests for the laboratory diagnosis
      of dengue virus infections are needed. OBJECTIVE: To develop a semi-nested
      polymerase chain reaction (PCR) assay based on primers within the NS3 gene for
      the simultaneous detection and typing of dengue viruses in human sera. STUDY
      DESIGN: A first round of single-step reverse transcription-polymerase chain
      reaction (RT-PCR) was carried out with a pair of consensus primers, followed by a
      second round of semi-nested amplification using the upstream consensus primer and
      four type-specific down-stream primers. The sensitivity and specificity of the
      semi-nested PCR assay were determined using plaque- or TCID(50)-titrated virus
      infected tissue culture fluid, and total RNA extracted from C6/36 cells infected
      with dengue and other flaviviruses, respectively. A retrospective study was
      performed on acute sera from thirteen patients with dengue (confirmed by virus
      isolation) employing semi-nested PCR in parallel with virus re-isolation and a
      single-step RT-PCR method for the typing of dengue viruses in human sera.
      RESULTS: The semi-nested PCR assay could detect up to 1 pfu of dengue virus, but
      not other flaviviruses. The semi-nested PCR and single-step RT-PCR assays
      correctly typed dengue viruses in twelve and five sera, respectively, whereas
      none of the sera was positive by virus re-isolation. CONCLUSIONS: This semi
      nested PCR assay is a sensitive and specific tool for the detection and typing of
      dengue viruses from viremic human sera.

PMID- 15566834
TI  - Polymerase chain reaction for the early diagnosis of cytomegalovirus hepatitis in
      liver transplant patients.
AB  - BACKGROUND: In liver transplant (LTX) patients, cytomegalovirus (CMV) hepatitis
      as a cause of graft dysfunction occurs in 15-25% of the patients. Polymerase
      chain reaction (PCR), applied to liver biopsy specimens, may increase the ability
      to detect CMV DNA at a local site. In this study, PCR was used to compare its
      relation to the development of clinical CMV hepatitis. STUDY DESIGN: Nested
      polymerase chain reaction (nPCR), derived from a conserved region of the CMV
      major immediate-early gene, was used to examine 141 frozen liver biopsies from 61
      LTX patients for the presence of CMV DNA. 134 biopsies were obtained from 54
      patients with pathological liver function tests within four months after
      transplantation. The remaining seven patient biopsies were derived from the one
      year investigation after LTX and served as controls. The results were compared to
      virus isolation, antigen detection by immunohistology and in situ hybridization
      for CMV DNA of the biopsy specimens. Histological examination was performed to
      verify a diagnosis of viral hepatitis. RESULTS: CMV DNA was amplified in 11%
      (15/134) of the biopsies, corresponding to 20% (11/54) of the patients. Virus
      isolation revealed CMV in 5% (7/134) of the samples. None of the nPCR-negative
      biopsies was virus culture positive. CMV genomes were detected by nPCR more
      frequently than CMV hepatitis was diagnosed by using the combination of CMV
      specific histopathology and/or immunohistology and/or CMV-positive virus
      isolation (p < 0.01). However, when this comparison was performed within
      individual patients, the difference was not significant (p > 0.05). If the
      results of in situ hybridization were included in the diagnostic criteria of CMV
      hepatitis, the nPCR was comparable to these, both at the biopsy and the patient
      levels (p > 0.1 and p > 0.05, respectively). For the diagnosis of CMV hepatitis
      the negative predictive value of CMV-nPCR was 1.0. The positive predictive value
      ranged from 0.55 to 0.82 depending on the criteria of CMV hepatitis. The nPCR
      also detected signs of CMV infection in the liver graft earlier than virus
      isolation, 11 versus 21 days, respectively, after transplantation. CONCLUSION:
      The frequency of CMV DNA positivity, measured by nPCR, was similar to that
      revealed by other combined methods. We suggest that the combined findings of
      histological cholangitis and/or lobulitis together with nPCR for CMV DNA can be
      used as a diagnostic criterion for initiation of antiviral treatment against CMV
      hepatitis.

PMID- 15566835
TI  - Antibody reactivity to individual structural proteins of measles virus in the CSF
      of SSPE and MS patients.
AB  - BACKGROUND: Chronic progressive disorders of the central nervous system (CNS)
      impose diagnostic problems, particularly in younger patients. The demonstration
      of antibodies against measles virus (MV) in the cerebrospinal fluid (CSF) plays a
      major role in the laboratory diagnosis of subacute sclerosing panencephalitis
      (SSPE) as well as multiple sclerosis (MS). OBJECTIVES: Because intrathecally
      synthesized antibodies against MV can be found in both diseases, it is necessary
      to establish easy and reliable methods to improve the differential diagnosis.
      STUDY DESIGN: Seventy-one paired serum/CSF samples obtained from patients with
      the diagnosis of SSPE (n = 23), MS (n = 14), or acute postinfectious measles
      encephalitis (APME, n = 8) have been examined. The reactivity of intrathecally
      synthesized immunoglobulin to individual recombinant MV structural proteins was
      assessed using Western blot analysis, ELISA as well as isoelectric focusing
      (IEF). RESULTS: All CSF samples obtained from patients suffering from SSPE showed
      a strong antibody response to MV-nucleocapsid (N) and phosphoprotein (P). Sera
      from 15 of the 23 SSPE patients were reactive to MV-fusion protein (F). Faint
      reactivity was obtained against MV-matrix (M) or hemagglutinin protein (H) in the
      minority of samples (40 and 20%, respectively). CSF samples of MS patients only
      revealed a clear response to N, and in two cases to F. The other proteins were
      not recognized in the CSF samples of MS patients. In contrast to SSPE, the IEF of
      CSF from MS patients revealed only few MV-specific oligoclonal bands. In the CSF
      samples from APME patients, intrathecal MV antibodies were not detected.
      CONCLUSIONS: This study shows that discrimination between SSPE and MS can be
      achieved in doubtful cases by IEF using MV-N, P and F proteins.

PMID- 15566836
TI  - Re-evaluation of anti-HTLV-I Western blot assay using HTLV-I and HTLV-II serum
      panels.
AB  - BACKGROUND: Western blot assay is accepted to be a confirmatory test of anti-HTLV
      I antibodies, and several WB criteria have been proposed for confirming HTLV-I
      seropositivity. There is a necessity for comprehensive study on the criteria.
      OBJECTIVES: This study was performed to evaluate anti-HTLV-I WB kits and
      feasibility of the WB criteria. STUDY DESIGN: We tested 3 commercially available
      WB kits: PROBLOT HTLV-I, Eitest ATL-WB and HTLV BLOT 2.2, by a standard HTLV-I
      serum panel which had been established in our previous study. Sensitivity and
      specificity to detect each component of HTLV-I antigens were evaluated by the
      correlation coefficient, R-value. Specificity of the anti-HTLV-I WB kits and HTLV
      BLOT 2.3 was further evaluated by a standard HTLV-II serum panel established from
      the HTLV-I/II epidemiological surveillance of Colombian natives. RESULTS: PROBLOT
      HTLV-I showed high R-values (>/=0.980) for p28, p53 and gp46, but low R-values
      (<0.900) for p19 and p24. Eitest ATL-WB showed a high R-value for p19, but low R
      values for p53, gp46 and rgp21. HTLV BLOT 2.2 showed high R-values for p28 and
      recombinant gp46-I, but low R-values for p53 and gp46. The HTLV-II serum panel
      showed positive reactions with p24 and p19 of HTLV-I but a little if any
      reactions with p28 and gp46 of HTLV-I. Although these reactions could not define
      HTLV-II-specific WB patterns in anti-HTLV-I WB, HTLV-I- and HTLV-II-specific
      recombinant gp46 in HTLV BLOT 2.3 were useful to distinguish anti-HTLV-II
      antibodies. CONCLUSIONS: The currently available anti-HTLV-I WB kits are
      sufficient for confirmatory testing of anti-HTLV-I antibodies with WHO criteria
      using one gag and one env positivity, but they are inadequate for anti-HTLV-II
      confirmatory testing.

PMID- 15566837
TI  - Early diagnosis of HIV-1 infection in infants in Dar es Salaam, Tanzania.
AB  - OBJECTIVES: To evaluate two simple methods, an immune complex dissociation (ICD)
      p24 antigen assay and an HIV-1-specific IgA antibody assay, for the early
      demonstration of HIV-1 infection in infants, using the polymerase chain reaction
      (PCR) as the reference method. DESIGN AND SETTING: Group A: 143 HIV-1
      seropositive and 134 -seronegative mothers and their infants were recruited at
      delivery at the main hospital in Dar es Salaam, Tanzania. Group B: 26 HIV-PCR
      positive hospitalized children in Dar es Salaam, 3-15 months old and suspected of
      having an HIV-related illness. METHODS: Blood samples were taken from mothers and
      infants in group A at intervals during the children's first 24 months and once
      from each of the children in group B. Peripheral blood mononuclear cells were
      tested by nested PCR for viral DNA. Plasma samples were tested by the Coulter p24
      antigen (ag) enzyme-linked immunosorbent assay (ELISA) after acid dissociation of
      p24 antigen-antibody complexes. All p24-ag-positive reactions were confirmed by
      neutralization. Viral specific IgA antibodies were demonstrated in plasma by a
      modified ELISA. RESULTS: One hundred and sixty-three of 174 samples from
      seropositive mothers were PCR-positive (sensitivity 93.7%) and 612 of 614 samples
      from seronegative mothers and children of seronegative mothers were PCR-negative
      (specificity 99.7%). Twenty-nine of 145 (20.0%) children born to seropositive
      mothers were positive by PCR when tested during the first year of life. By use of
      both the p24 ag ELISA and the IgA antibody ELISA in combination, HIV-1 infection
      was detected in 9 of 17 (53%) PCR-positive children 1-8 weeks old, in 15 of 18
      (83%) PCR-positive children 9-26 weeks old and in 23 of 24 (96%) PCR-positive
      children 27-52 weeks old. The specificities of the p24 ag ELISA and the IgA ELISA
      were 100%. CONCLUSIONS: The p24 ag assay and the IgA antibody ELISA, when used in
      combination, had a high sensitivity and specificity for detection of HIV-1
      infection in infants, especially in those above the age of 6 months.

PMID- 15566838
TI  - Rapid detection of HSV with an enzyme-linked virus inducible system (ELVIS)
      employing a genetically modified cell line.
AB  - BACKGROUND: Infections with herpes simplex viruses (HSV) are common and may cause
      severe disease in immunocompromised hosts and in neonates. Isolation of
      infectious HSV in tissue culture is the most sensitive method of detection, but
      is not the most rapid. Recently, however, an Enzyme-Linked Virus Inducible System
      (ELVIS) for rapid detection of HSV in culture has been developed. The system
      employs genetically engineered baby hamster kidney (BHK) cells (ELVIS cells)
      whose DNA bears and HSV inducible promoter gene chimerically linked to an E. coli
      LacZ "reporter" gene. Induction of the promoter by HSV leads to the production of
      LacZ product, beta-galactosidase, which is readily detected histochemically.
      OBJECTIVE: To evaluate these ELVIS cells, as a test for HSV, in comparison with
      HSV detection in MRC-5 cells in shell vial cultures confirmed by staining with
      fluorescent antibodies. STUDY DESIGN: Over a period of one month, 167 specimens
      submitted to the laboratory for detection of HSV were evaluated. Specimens were
      inoculated onto MRC-5 cells growing on glass coverslips in each of two shell
      vials and into two wells of a 24-well cluster plate containing ELVIS cells. MRC-5
      shell vial cultures were observed daily for cpe for up to 7 days. With the
      appearance of cpe, the coverslips were fixed and the cells were typed for HSV-1
      and HSV-2 with monoclonal antibodies. Specimens inoculated onto ELVIS cells were
      incubated for 16-24 h, then substrate was added to stain for beta-galactosidase.
      ELVIS cells, induced by HSV infection to express beta-galactosidase, stained blue
      upon reaction with substrate. RESULTS: Of 167 specimens inoculated onto MRC-5
      cells, 13 were excluded because of contamination or toxicity. Among the remaining
      154 specimens, 24 were positive for HSV in the MRC-5 shell vials. Of 166
      specimens inoculated into the ELVIS cell, all were completed within 24 h. Twenty
      three (23) of the 24 shell-vial-positive cultures also were positive on the ELVIS
      cells. All 23 specimens detected in the ELVIS cells were positive within 24 h,
      whereas only nine were positive within 24 hours in MRC-5 shell vial cultures. The
      remaining 15 became positive after 24 h. Specimens positive for viruses other
      than HSV-1 or HSV-2 were not positive on the ELVIS cells. CONCLUSIONS: The ELVIS
      assay for HSV is simple to perform, is rapid, sensitive, and specific. The assay
      detects both HSV-1 and HSV-2. No antibodies are required unless typing, which can
      be done on the ELVIS cells, is necessary.

PMID- 15566839
TI  - The JC virus antibody response in serum and cerebrospinal fluid in progressive
      multifocal leucoencephalopathy.
AB  - BACKGROUND: A clinical diagnosis of progressive multifocal leucoencephalopathy
      (PML) can be confirmed by histological or virological examination of brain
      material. Whilst a less invasive method is provided by the detection of JC DNA in
      cerebrospinal fluid (CSF), very few studies have been done to assess the value of
      JC virus (JCV) serology in PML diagnosis. OBJECTIVES: To study the JCV antibody
      response in the serum and CSF of PML patients. STUDY DESIGN: A retrospective
      study was done using haemagglutination inhibition (HI), M-antibody capture
      radioimmunoassay (MACRIA) and JC-specific oligoclonal IgG banding on one or more
      sera and/or CSFs from 28 confirmed PML patients. Seventy-one serum and CSF
      samples were tested from patients with memory loss or dementia as a control
      group. RESULTS: Twenty-seven PML patients (96%) had detectable JCV HI antibody in
      the serum, with titres ranging from 1 : 10 to > 1 : 20480, compared to 48 (68%)
      of the controls (P = <0.005). JCV IgM antibody was detected in the serum of 12/22
      (55%) PML patients. JCV HI antibody was detected in the CSF in 12 of 18 (67%) PML
      patients, antibody index measurements being used to control for a possible
      breakdown of the blood-brain barrier. Intrathecal JCV antibody was not found in
      any control patient. Locally produced JCV-specific IgG bands were detected in the
      CSF of 7 PML patients tested, confirming the intrathecal origin and specificity
      of the HI antibody. CONCLUSIONS: The presence of intrathecal JCV antibody
      indicates active central nervous system infection with JC virus, and provides a
      useful diagnostic test for PML, with a sensitivity of 67% and a specificity of
      100%. The absence of serum JCV antibody nearly always excludes a diagnosis of
      PML, but the titre of antibody, IgG or IgM, correlates with the underlying
      condition rather than the development of neurological symptoms.

PMID- 15566840
TI  - Specific enzyme immunoassays for the rapid detection of Ross River virus in cell
      cultures inoculated with infected mosquito homogenates.
AB  - BACKGROUND: Ross River (RR) virus is a mosquito-borne alphavirus and one of the
      aetiological agents of epidemic polyarthritis in humans. Early detection of
      increased virus activity in mosquito populations enables public health
      authorities to implement measures to reduce the number of human infections during
      epidemics. However, current surveillance techniques require a minimum of four
      weeks for viruses to be isolated and identified. OBJECTIVES: This study was
      carried out to assess the use of enzyme immunoassays (EIA) as rapid alternatives
      to traditional cell culture techniques for detection of RR virus in mosquitoes.
      STUDY DESIGN: Enzyme immunoassays and immunoperoxidase assays were developed
      using RR-specific monoclonal antibodies and compared to traditional methods for
      detection of RR virus in field-caught mosquito samples. RESULTS: By inoculation
      of C6/36 cell cultures with mosquito homogenates and testing monolayers and
      culture supernatant by EIA, RR virus was detected and identified in all infected
      samples within 6 days. CONCLUSIONS: The use of EIA provides a rapid, sensitive
      and specific alternative to traditional methods for the detection of RR virus in
      mosquito vectors.

PMID- 15566841
TI  - Adult dengue deaths in Singapore.
AB  - BACKGROUND: Dengue haemorrhagic fever (DHF) is a leading cause of hospitalization
      of children in Southeast Asia and regarded mainly as a problem of childhood. In
      Singapore, however, both dengue fever (DF) and DHF now occur most frequently in
      those aged 16-25 years and case fatality rates are higher among adults than
      children. OBJECTIVE: To describe adults who died from DHF in Singapore. STUDY
      DESIGN: The clinical, laboratory and, where performed, autopsy records of adults
      reported to the Ministry of the Environment to have died from DHF were reviewed.
      RESULTS: Four of 10 adults had clinical, serological and/or virological evidence
      of acute dengue virus infection. All 4 patients, who were between 27 and 58 years
      old, had dengue IgM antibodies. Two of them had elevated dengue IgG antibodies
      consistent with a recent infection. Dengue type 2 virus was isolated from one of
      these two patients who had bled into the lungs, skin, pericardial and pleural
      surfaces and succumbed to shock. The other patient had no evidence of overt
      bleeding. A third patient, who suffered massive intractable retroperitoneal
      haemorrhage and shock, seroconverted in the haemagglutination inhibition test for
      dengue antibodies. The fourth patient had bleeding into her skin, urinary and
      gastrointestinal tracts, acute pulmonary oedema, ascites and hypotension. Her
      stillborn baby also had ascites. CONCLUSION: Deaths from DHF are not mainly a
      childhood occurrence. Adults do die from severe DHF, whether the infection be
      primary or secondary.

PMID- 15566842
TI  - No association of JC virus with Alzheimer's disease or astrocytomas.
AB  - OBJECTIVES: To investigate if JC virus (JCV) can be involved in the pathogenesis
      of Alzheimer's disease (AD) and astrocytomas. STUDY DESIGN: A nested polymerase
      chain reaction (PCR) was used for the detection of JCV DNA in autopsy brain
      material (cerebral white matter) and cerebrospinal fluid (CSF) specimens from
      patients with AD and age-matched control patients without neurological diseases,
      together with biopsies from patients with astrocytomas (grades 3 and 4). Brain
      autopsy material from AIDS patients with progressive multifocal
      leukoencephalopathy (PML) was examined as positive control material. RESULTS: JCV
      DNA was detected by PCR in only one of the 17 brain autopsies from patients with
      AD, but in none of the 26 control patients without neurological diseases and in
      none of the 5 astrocytoma biopsies. JCV DNA was, however, detected in the brain
      material from two patients with PML. CONCLUSION: Our results show that JCV
      infection does not seem to be directly involved in the pathology of AD or in the
      development of astrocytomas. In addition, since no viral DNA was detected in CSF
      specimens from 43 patients without PML (17 with AD and 26 elderly controls), our
      results suggest that the finding of JCV DNA in CSF correlates to PML.

PMID- 15566843
TI  - Requirements for diagnosis of prenatal cytomegalovirus infection by amniotic
      fluid culture.
AB  - BACKGROUND: Amniotic fluid culture is considered to be the best method for the
      detection of antenatal cytomegalovirus (CMV) infection and prediction of
      congenital CMV infection. Recently, however, some false-negative results have
      been reported. OBJECTIVES: Prediction of congenital CMV infection by amniotic
      fluid culture with emphasis on false-negative results. STUDY DESIGN:
      Retrospective study of 42 pregnant women with primary CMV infection. First,
      estimation of seroconversion related to the gestational age was established.
      Afterwards, results of amniotic fluid culture were compared either with CMV
      isolation from biopsies from aborted fetuses, or with viral culture of newborns'
      urine. RESULTS: In 18 cases (43%), amniotic fluid culture gave negative results
      which coincided with 18 uninfected newborns. In 18 other cases (43%), amniotic
      fluid culture was positive for CMV: 7 newborns with CMV viruria and 11
      terminations of pregnancy with CMV isolated from fetal biopsies. In the remaining
      6 cases, amniotic fluid culture gave negative results, whereas the 6 newborns
      were all infected. CONCLUSION: Amniotic fluid culture remains an accurate method
      for the diagnosis of CMV antenatal infection. However, in order to avoid false
      negative results, the importance of a correct estimation of the gestational age
      of seroconversion and of a sufficient interval between primary infection and
      amniocentesis are stressed.

PMID- 15566844
TI  - Detection of hepatitis C viral sequences in serum by 'nested' polymerase chain
      reaction (PCR) and a commercial single-round PCR assay.
AB  - BACKGROUND: Demonstration of the hepatitis C virus (HCV) genome is usually done
      with combined reverse transcription and polymerase chain reaction (RT-PCR)
      employing nested primer sets. Recently, a commercial PCR assay (Amplicor PCR
      assay), based on a simplified sample preparation procedure, a single, combined
      reverse transcription and polymerase chain reaction (RT-PCR), and a microwell
      plate capture and detection, has been developed. OBJECTIVE: The aim of the
      present study was to compare the new Amplicor assay with an 'in-house' PCR.
      Additional testing included a third-generation enzyme immunoassay for anti-HCV
      antibodies, the Wellcozyme HCV Western Blot, which is equivalent to a third
      generation recombinant immunoblot assay. Furthermore, HCV genotypes were
      classified. STUDY DESIGN: Sera from a total of 127 patients were studied. After
      screening with a third-generation enzyme immunoassay (EIA), the Wellcozyme HCV
      Western Blot, was performed as well as the conventional RT-PCR and the Amplicor
      PCR. Specimens, which were found positive by testing with the Amplicor kit, were
      subjected to storage at room temperature for 96 h. RESULTS: A total of 52
      patients were found to be positive for anti-HCV by the third-generation EIA. With
      the Amplicor assay, the HCV genome was detected in 38 patients. In comparison
      with the 'in-house' assay, two discrepant results were found. Resolution of
      discrepant samples increased the total number of true positives to 39. A good
      correlation was found between a positive anti-HCV test result and the presence of
      HCV-RNA by RT-PCR. No significant reduction in the amount of amplification
      product was observed by retesting of suboptimally stored samples with the
      Amplicor assay. CONCLUSION: Because of the rapidity and the improved ease of
      handling, the Amplicor assay was found to be a good contribution for detection of
      HCV in serum.

PMID- 15566845
TI  - Rapid culture for influenza virus, types A and B, in 96-well plates.
AB  - BACKGROUND: Rapid diagnosis and typing of influenza virus are important for
      patient treatment and management during seasonal outbreaks. Centrifugation
      enhanced rapid culture has been reported to be useful as an adjunct to
      traditional tube culture for rapid diagnosis of influenza virus. OBJECTIVES: We
      compared rapid culture in 96-well plates against standard tube culture for
      recovery of influenza virus, types A and B. We also tested two different cell
      types, MDCK and RMK, to determine if the use of multiple cell lines increases the
      sensitivity of rapid culture. STUDY DESIGN: The rapid method was initially
      evaluated by retrospective culture of previously positive frozen specimens. It
      was then compared to standard culture for recovery of influenza virus by parallel
      testing of fresh respiratory specimens. RESULTS: Of 32 previously positive frozen
      specimens, 28 were positive upon repeat culture. Rapid culture recovered 25
      (89.3%) and standard culture recovered 23 (82.1%). All positives were type A. Of
      722 fresh specimens cultured in parallel, 76 (10.5%) were positive for influenza
      virus: 43 for type A and 33 for type B. For type A, rapid culture recovered 42 of
      43 (97.7%) and tube culture recovered 39 (90.7%). For type B, rapid culture
      recovered 33 of 33 (100%) and tube culture recovered 24 (72.7%). In the rapid
      system, the MDCK cell line was positive for 40 of 42 type A positives (95.2%) and
      the RMK was positive for 41 (97.6%). The MDCK line was positive for 32 of the 33
      type B isolates (97.0%) and the RMK cells were positive for all 33 (100%).
      CONCLUSIONS: Rapid culture substantially reduced total test time and was more
      sensitive than tube culture. Duplicate cell lines did not significantly increase
      test sensitivity.

PMID- 15566846
TI  - Detection of Ross River virus in clinical samples using a nested reverse
      transcription-polymerase chain reaction.
AB  - BACKGROUND: Ross River virus (RRV) is a mosquito borne alphavirus that has been
      found in Australia, Papua New Guinea and the Pacific Islands. It is aetiological
      agent of epidemic polyarthritis, a debilitating illness whose symptoms are
      arthritis, arthralgia, lethargy, rash and fever which may persist for weeks or
      months. Diagnosis is made on a serological basis, but in many cases is
      presumptive rather than definite. OBJECTIVES: To apply the polymerase chain
      reaction (PCR) to detection of RRV in human sera to assess its suitability for
      application in disease diagnosis. STUDY DESIGN: Sensitivity of the nested RT-PCR
      assay was determined by detection of virus of known titre diluted in uninfected
      serum. Clinical serum samples from patients serologically diagnosed of having RRV
      infection were tested by nested RT-PCR to assess its diagnostic value. RESULTS:
      Sensitivity of the nested RT-PCR assay was determined to be detection of 0.01 PFU
      of virus stock in 100 mul serum. Clinical samples tested showed that 10 of 26
      (38%) serum samples with low or negative (non-diagnostic) virus-specific antibody
      titres were PCR-positive, whereas all 22 specimens with high antibody titres were
      PCR-negative. PCR positivity was unaffected by repeated freezing and thawing of
      samples. CONCLUSIONS: While PCR cannot replace serology as a means of RRV
      diagnosis, it may be useful in conjunction with serological testing, particularly
      for forming definitive diagnoses in those samples with low (inconclusive)
      antibody titres. It is faster and more sensitive than virus isolation by tissue
      culture, and could also prove useful in investigations of disease pathogenesis.

PMID- 15566847
TI  - Use of continuous human lung cells in the laboratory diagnosis of respiratory
      syncytial virus.

PMID- 15566848
TI  - Hepatitis C in Lithuania: incidence, prevalence, risk factors and viral
      genotypes.
AB  - BACKGROUND: The epidemiology of hepatitis C virus (HCV) infection has been
      studied in many countries. However, little is known about HCV infection in
      Lithuania, a Baltic country, that was part of the former Soviet Union.
      OBJECTIVES: The aim of this study was to determine and evaluate the etiology of
      acute viral hepatitis, the risk factors for acquiring HCV in comparison to
      hepatitis B virus (HBV), seroprevalence of anti-HCV among blood donors and risk
      groups of the population in Lithuania. The distribution of HCV genotypes from
      Lithuanian first-time blood donors was also assessed. STUDY DESIGN: Sera taken
      from clinical viral hepatitis patients, blood donors, risk groups of population
      were investigated serologically. Patients with acute viral hepatitis were
      interviewed to determine their risk factors for HCV and HBV. HCV genotyping was
      done by PCR using type specific primers. RESULTS: Acute hepatitis C accounted for
      5.0-8.5% of reported viral hepatitis cases in adults in Vilnius. Of the acute
      hepatitis C cases, 37.0% was associated with blood transfusions before the
      implementation of screening of blood donors for anti-HCV and only 15.4% (2/13)
      after the screening was started. Anti-HCV was found in 2.2% of first-time blood
      donors, in 7.9% of commercial blood donors, in 13.9% of commercial blood plasma
      donors, in 48.3% of hemodialysis patients, in 29.4% of prisoners, in 9.4% of
      elderly nursing home residents, and in 7.9% of hemodialysis staff. The following
      distribution in genotypes were found: genotype 1b (54.3%), 3a (23.9%), 2a (10.9%)
      2b (4.3%), 1a (0%), and double infection (6.5%). CONCLUSIONS: Lithuania is a
      country with a considerable hepatitis C problem.

PMID- 15566849
TI  - Markedly elevated levels of beta2-microglobulin in urine with measles viruria in
      patients with measles.
AB  - BACKGROUND: Measles is a highly contagious infectious disease in children.
      However, the pathogenesis has not yet been fully defined since susceptible cells
      to measles virus (MV) had not been developed. Recently, B95a cells, which are
      very susceptible to MV, have been reported. OBJECTIVES: To evaluate measles
      viruria in patients with measles, isolation of MV from urine was performed using
      B95a cells. STUDY DESIGN: Isolation of MV from supernates or sediments of urine
      in patients with measles was performed using B95a cells. The levels of beta2
      microglobulin (MG) in urine and serum were also measured. RESULTS: MV was
      isolated from either supernates or sediments of urine. MV was isolated from 10 of
      11 samples (91%) within 2 days of the appearance of a rash. MV was isolated from
      supernates of urine for up to 4 days after the appearance of a rash, and from
      sediments for up to 5 days. The levels of urinary beta2-MG were elevated within 2
      days of the appearance of a rash. The levels of urinary beta2-MG with measles
      viruria were significantly higher compared to those without measles viruria.
      CONCLUSIONS: Measles viruria may occur early in all patients with measles and
      elevated levels of urinary beta2-MG in patients with measles may be the
      consequence of tubular injury.

PMID- 15566850
TI  - IgM anti-hepatitis C virus in patients with chronic non-A, non-B hepatitis and
      their relationship to viral replication.
AB  - Patients with hepatitis C virus (HCV) infection may have different patterns of
      antibody response to various structural and non-structural viral antigens. We
      have correlated the serological patterns to the clinical features of chronic
      infection and to viral replication in 68 HCV-Ab-positive patients with chronic
      liver disease at different stages (19 with cirrhosis-hepatocellular carcinoma, 38
      with chronic active hepatitis and 11 with chronic persistent hepatitis). Serum
      samples from each patient were assayed for HCV-IgM by enzyme immunoassay and for
      HCV-RNA by the polymerase chain reaction using primer sets derived from the 5'
      non-coding region. The prevalence of HCV-IgM was high (54 patients (79.4%)) and
      the study showed a good correlation between high values of anti-HCV-IgM and the
      presence of HCV-RNA in serum, since HCV-RNA was detected in 35 of the 54 IgM
      positive patients (64.8%) and notably in 19 of the 20 subjects with high levels
      of specific IgM. Conversely, all the 35 sera containing HCV-RNA were also
      reactive for HCV-IgM, while none of the HCV-IgM-negative sera was HCV-RNA
      reactive. Positivity rates for both HCV-RNA and IgM anti-HCV were higher in the
      more advanced stages of disease; thus, the clinical pattern of HCV chronic
      hepatitis seems to be strictly related to the serological pattern and the
      presence of HCV-RNA.

PMID- 15566851
TI  - Cytomegalovirus-caused release of collagenase IV from human cerebral
      microvascular endothelial cells.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) in most normal individuals results in an
      asymptomatic infection, but under some circumstances, such as in the transplant
      setting, AIDS and intrauterine infection of the fetus, HCMV infection can lead to
      more serious consequences, including central nervous system infection. Recently
      it has been demonstrated that HCMV-infected endothelial cells can be detected in
      the circulation; however, no mechanism has been suggested. OBJECTIVE: To
      determine whether HCMV infection of confluent human microvascular endothelial
      cells (HMEC) in culture results in the induction of type IV collagenase. This
      would provide a mechanism by which HCMV-infected HMECs could be released into the
      circulation. STUDY DESIGN: Confluent cultures of brain-derived HMECs were
      infected with HCMV and culture supernatants were sampled for collagenase IV,
      general protease and viral titers. RESULTS: HCMV infection of HMECs stimulated a
      significant release of collagenase type IV activity which peaked early in the
      assay within 3-5 days and fell off rapidly thereafter. This stimulation of
      protease activity differed only slightly between non-infected and infected
      cultures. By day 6, viral cytopathic effects became evident and HCMV titers
      reached approximately 5 x 10(5) PFU/ml by day 9. CONCLUSIONS: These results
      demonstrate that HCMV infection of HMEC induces the release of collagenase type
      IV. This may lead to the degradation of the basement membrane and subsequently to
      the release of fully infected endothelial cells into the circulation resulting in
      further dissemination of the infection.

PMID- 15566852
TI  - Evaluation and comparison of the Amplicor HIV-1 PCR kit with an 'in-house' nested
      PCR.
AB  - BACKGROUND: The polymerase chain reaction (PCR), a powerful gene amplification
      technique, is moving rapidly from the research laboratory into routine clinical
      use. OBJECTIVES: To evaluate the specificity and sensitivity of a commercially
      available PCR kit, the Amplicor HIV-1 PCR kit (AMP) and to compare it with an in
      house nested PCR, which amplified part of the POL gene (POL(n)). STUDY DESIGN: A
      total of 517 samples were tested by AMP, including 159 fresh whole blood
      specimens from HIV-1 antibody positive Europeans and 358 archival samples (338
      seropositive and 20 seronegative individuals) originating from 35 different
      countries in Africa and Europe. We compared the performance of AMP on the
      archival samples with POL(n). RESULTS: The overall sensitivity and specificity as
      compared to HIV-1 serology were 93% and 100%, and 96% and 100%, for AMP and the
      in-house PCR, respectively. Repeat testing on co-cultured lymphocytes increased
      the sensitivity of AMP to 95%. CONCLUSIONS: AMP is a rapid, and easy to use
      commercially available PCR kit, since only one amplification of the test sample
      is required. Moreover, the use of radioactivity is omitted, and reading of the
      test can be done with a spectrophotometer. The use of at least one additional
      primer pair may increase confidence in distinguishing a positive and negative
      sample by both PCR techniques.

PMID- 15566853
TI  - Identification of tick-borne encephalitis virus ribonucleic acid in tick
      suspensions and in clinical specimens by a reverse transcription-nested
      polymerase chain reaction assay.
AB  - BACKGROUND: Tick-borne encephalitis virus (TBEV) is a major human pathogenic
      flavivirus. Sensitive assays for the detection of viral RNA may be valuable both
      for the identification of virus in ticks as well as for diagnostic purposes.
      OBJECTIVES: (1) The development of a sensitive polymerase chain reaction (PCR)
      test system for the detection of TBEV-RNA and its application to the
      identification of infected ticks; and (2) evaluation of the PCR assay for
      diagnostic purposes, i.e., detection of TBE virus RNA in blood and in
      cerebrospinal fluid (CSF) of TBE patients. STUDY DESIGN: (1) Establishment of a
      TBEV-specific reverse transcription (RT)-nested PCR assay and evaluation of its
      sensitivity; (2) comparison of the PCR assay with that of virus isolation from
      tick suspensions; and (3) investigation of 105; serum and CSF samples from
      patients with serologically confirmed TBE by RT-nested PCR. RESULTS: An RT-nested
      PCR assay was established with a detection limit of 100-1000 copies of TBEV RNA.
      All tick suspensions from which the virus could be isolated by inoculation of
      suckling mice also screened positive in the PCR assay. Of the 105 clinical
      samples investigated, only one serum and one CSF sample were positive by PCR
      assay, and these were both obtained very early in the course of the disease.
      CONCLUSIONS: The PCR assay described is valuable for the detection of TBEV in
      tick suspensions and can substitute for the usual virus isolation procedure in
      which suckling mice are inoculated. Its application for diagnostic purposes,
      however, does not seem to provide a significant improvement over serological
      diagnosis. Only in very rare cases, when a sample is drawn extremely early in the
      course of disease, may TBEV RNA be detected in serum or CSF before the appearance
      of specific IgM antibodies and thus allow an earlier diagnosis.

PMID- 15566854
TI  - Detection of an RNA-dependent DNA polymerase activity.

PMID- 15566855
TI  - How valuable are IgA and IgM anti-HIV tests for the diagnosis of mother-child
      transmission of HIV in an African setting?
AB  - BACKGROUND: Babies born to HIV-infected mothers retain anti-HIV of maternal
      origin until 15-18 months of age. Because of this, HIV proviral DNA and p24
      antigen measurements have become the methods of choice for timely diagnosis of
      HIV infection in infancy. They are, however, too expensive for widespread use in
      the developing world. OBJECTIVE: To evaluate a simple, inexpensive serological
      method for diagnosing mother-child transmission of HIV, in an African population,
      which takes account of the effects of placental transfer of maternal antibody and
      continued exposure to HIV through breast-feeding. STUDY DESIGN: Plasma specimens
      for a prospective study of mother-to-infant transmission of HIV in rural Zaire
      were collected at birth, 3, 6, 9, 12, 18 and 24 months from 21 infected infants
      (PP group), 21 uninfected infants (PN group) born to seropositive mothers and 21
      control infants (NN group) born to uninfected mothers. The specimens were
      retrospectively tested for IgG, IgM and IgA anti-HIV by immunoglobulin class
      specific capture EIAs, and by a commercial anti-HIV EIA. RESULTS: In neonatal
      specimens, IgA and IgM anti-HIV were present, respectively, in 13 of 14 (97%) and
      8 of 14 (57%) of the PP group and in 6 of 11 (55%) and 2 of 11 (18%) of the PN
      group. Later, at 3 months and older, IgA and IgM anti-HIV were only detected in
      the PP group. They peaked at 18 months (93%) and 24 months (67%) respectively. Of
      the 21 PP group children, 8 (38%) were transiently IgG anti-HIV-negative in the
      first year, indicating that infection had probably taken place after birth; four
      of the 8 had no detectable IgA anti-HIV during the first year. None of the
      specimens collected from the NN group babies were reactive for IgA, IgM or IgG
      anti-HIV. CONCLUSIONS: IgA and IgM anti-HIV may be passively transferred across
      the placenta. Where breast-feeding is prevalent, about half of the transmissions
      may occur after birth, thus delaying the diagnosis of mother-child transmission.
      Nevertheless, this simple, cheap IgA anti-HIV, EIA identified 65% of
      transmissions by 9 months of age, and 93% at 18 months of age. It is a more
      useful marker than IgM anti-HIV, and gave a much more rapid answer than did tests
      for IgG anti-HIV seroreversion.

PMID- 15566856
TI  - Evaluation of recombinant rubella-like particles in a commercial immunoassay for
      the detection of anti-rubella IgG.
AB  - BACKGROUND: We have investigated the performance of the novel rubella serology
      assay, Cobas Core Rubella IgG EIA recomb, which uses rubella-like particles
      (RLPs) expressed in transfected BHK-21 cells as the antigen. STUDY DESIGN:
      Evaluation of the assay included comparison with the hemagglutination inhibition
      (HAI) assay and another enzyme immunoassay (EIA) using native rubella virus (RV)
      as antigen, i.e. the Abbott IMx Rubella IgG. The assay was calibrated against the
      WHO 1000 IU/ml reference serum and showed good correlation with the HAI test in
      the analysis of 404 serum samples. However, quantitative differences in IgG
      values measured in the Cobas Core and the Abbott IMx assays were noted. RESULTS:
      Values obtained for patient sera as well as CDC and WHO standards were generally
      more than twice as high in the Abbott IMx assay as in the Cobas Core test.
      CONCLUSIONS: For sera whose IgG levels in the immunoassay and HAI test were
      discordant, immunoblotting proved valuable as a confirmatory method and indicated
      that a significant number of HAI-negative samples were correctly interpreted as
      positive by the immunoassay.

PMID- 15566857
TI  - Evaluation of 15 commercial enzyme immunoassays for the detection of rubella
      specific IgM.
AB  - BACKGROUND: Detection of rubella-specific IgM is a critical investigation in the
      diagnosis of recent or congenital rubella for which many commercial enzyme
      immunoassays (EIAs) are now available. OBJECTIVES: To evaluate 15 commercially
      available EIA kits for the detection of rubella-specific IgM. STUDY DESIGN: A
      panel of 229 sera was established comprising 72 sera from cases of primary
      rubella, re-infection, congenital rubella and primary immunization in which
      rubella-specific IgM had been detected by M-antibody capture radioimmunoassay
      (MACRIA); 80 sera, negative by MACRIA and no evidence of recent illness; 77 sera
      from recent illness with a number of other microbial agents, sera containing
      rheumatoid factor, and sera previously shown to give non-specific reactivity by
      MACRIA. These sera were tested in 15 commercial EIA kits for rubella-specific IgM
      according to the manufacturers' instructions. Sensitivity and specificity for
      each assay was established. RESULTS: Specificities ranged from 82-98%, improving
      to 88-100% if the previously established non-specific reactive sera were
      excluded. Sensitivities ranged from 63-92%. Although only two sera from
      congenital rubella were tested, for one serum only four assays detected specific
      IgM. CONCLUSION: Some commercial EIAs for rubella-specific IgM now give an
      acceptable balance of sensitivity and specificity, but all assays may give
      reactivity with occasional sera where there is no supporting evidence for recent
      primary rubella or rubella reinfection.

PMID- 15566858
TI  - Evaluation of an antigen capture ELISA based on recombinant mexico virus capsid
      protein.
AB  - BACKGROUND: The diagnosis of gastrointestinal infections caused by small round
      structured viruses (SRSV) has relied upon electron microscopy and
      antigen/antibody assays based on Norwalk virus. We investigated cases of
      gastroenteritis associated with SRSVs employing a new sandwich enzyme-linked
      immunosorbent assay (ELISA) using hyperimmune animal anti-sera against
      recombinant Mexico virus capsid protein (rMXV). STUDY DESIGN: One hundred and
      thirty-five specimens from 86 episodes of gastroenteritis associated with SRSVs,
      collected in the UK between October 1993 and September 1994, were tested in the
      rMXV assay. RESULTS: Forty-seven (35%) specimens from 35 of 86 (41%) episodes
      were positive in the rMXV ELISA and these could further be divided into high and
      low reactors. Sequencing of a 266-base region of the RNA polymerase gene revealed
      that strains highly reactive in the rMXV assay demonstrated a high degree of
      similarity to MXV (97-99% at the nucleotide level), whereas low-reactive strains
      consist of Mexico-like strains and a heterogeneous group of viruses exhibiting 70
      75% similarity to MXV. CONCLUSION: Our results indicate that the rMXV ELISA is
      predominantly a type specific assay, although some cross reactivity with other
      genogroup 2 SRSVs was observed. MXV was responsible for 26% of SRSV-associated
      gastrointestinal infections investigated in the UK during one year's
      surveillance.

PMID- 15566859
TI  - Detection by polymerase chain reaction of wild-type measles virus genome in the
      cerebrospinal fluid of a patient with SSPE who had received measles vaccine.
AB  - BACKGROUND: Previous studies have reported that approximately 4-5% of patients
      with subacute sclerosing panencephalitis (SSPE) were given measles vaccination
      but had no history of natural measles. However, in the case who received measles
      vaccine, it has been extremely difficult to determine whether the actual cause of
      SSPE is the inoculated vaccine virus or not. OBJECTIVES: To detect the measles
      virus genome in a patient with SSPE and to analyze its nucleotide and deduced
      amino acid sequence. STUDY DESIGN: We applied the polymerase chain reaction (PCR)
      to detect the measles virus genome in specimens from a 12-year-old boy with SSPE
      who had received measles vaccine 10 years before and had no history of apparent
      natural measles. The oligonucleotide primers for PCR were prepared based on the
      nucleotide sequence of the F and NP genes of the measles virus Edmonston strain.
      RESULTS: F and NP genes were detected in both the cerebrospinal fluid and
      peripheral blood lymphocytes. Nucleotide and deduced amino acid sequence analysis
      of the F gene showed that the patient's virus was different from that of the
      vaccine strain. Judging from these results, it was likely that the SSPE
      associated strain in this case was derived from the wild-type rather than the
      vaccine strain. CONCLUSIONS: PCR is a useful method to establish a definitive
      diagnosis of SSPE and to study the nature of the SSPE-associated virus.

PMID- 15566860
TI  - Detectionof reverse transcriptase activity in live attenuated virus vaccines.
AB  - BACKGROUND: Safety considerations require that biological products for human use
      are free from any agent that might pose a potential health hazard. One method to
      detect the presence of retroviral particles is the reverse transcriptase (RT)
      assay. This assay is capable of detecting all infectious retrovirus particles,
      irrespective of genome or protein composition. Recently, a family of
      ultrasensitive RT tests, named product-enhanced reverse transcriptase (PERT)
      assays, has been designed with a detection limit that is 10(6) - 10(7) times
      lower than that of conventional RT tests. OBJECTIVES: To investigate with the
      PERT assay whether RT activity is detectable in live attenuated virus vaccines
      and to characterize eventual RT activities. STUDY DESIGN: A total of 12 different
      monovalent and one trivalent virus vaccines containing live attenuated viruses
      were tested for RT activity with the PERT assay and a conventional RT test. RT
      activities were investigated with respect to their susceptibility to RT
      inhibitors, association with physical particles, and their possible origin.
      RESULTS: One trivalent and five different monovalent vaccines contained RT
      activity when tested with the PERT assay, but were negative in a conventional RT
      assay. All lots tested of these vaccines showed RT activity. The activity in all
      vaccines was sensitive to AZT-triphosphate and ddTTP and at least part of it was
      associated with particles. Mg(2+)-dependent RT activity banded at a density of
      1.14 g/ml. All positive vaccines were produced using chicken cells. CONCLUSIONS:
      The data indicate the systematic presence of partially particle-associated
      retroviral reverse transcriptase in attenuated live virus vaccines that are
      produced in chicken-derived cells. The identification and further
      characterization of these particles, as well as the elucidation of possible
      interactions with the human organism are imperative goals despite the fact that
      these vaccines have been safely used for many years.

PMID- 15566861
TI  - Detection of the 5' region of the rubella virus genome in clinical samples by
      polymerase chain reaction.
AB  - BACKGROUND: Maternal rubella infection in early pregnancy has a high probability
      of causing congenital rubella infection. In some cases it may be difficult to
      establish the risk of congenital infection and polymerase chain reaction (PCR)
      based techniques are therefore being applied to prenatal diagnosis. OBJECTIVES:
      To investigate whether the non-structural region of the rubella virus (RV) genome
      can be detected in clinical samples using PCR, thereby providing a prenatal assay
      independent of those currently used to detect the structural protein coding
      region. STUDY DESIGN: Oligonucleotide primers coding for RV nucleotides 1-17 and
      541-558 from the non-structural protein coding region of the RV genome were used
      in a reverse transcription polymerase chain reaction (NS RT-PCR) to amplify 558
      nucleotides of RV cDNA. Amplification of RV specific sequences was confirmed by
      Southern hybridization. RESULTS: The specificity of the assay was confirmed by
      the detection of RV RNA from both wild-type and vaccine strains of RV, pharyngeal
      swabs from two adult males with acute rubella and products of conception from
      three women with serologically confirmed primary rubella in pregnancy. RV RNA was
      not detected in uninfected HEL and Vero cells or peripheral blood mononuclear
      cells. The results were concordant with those of an RT-PCR directed to the E1
      protein coding region and with virus isolation. CONCLUSIONS: Detection of the non
      structural coding region of the RV genome in clinical samples suggests that NS RT
      PCR could be used as a confirmatory assay for prenatal diagnosis of congenital
      rubella, and that it will be of value for the identification of nucleotide
      changes in the 5' region of the RV genome.

PMID- 15566862
TI  - Improved detection of varicella zoster infection with a spin amplification shell
      vial technique and blind passage.
AB  - BACKGROUND: Among the methods available for the diagnosis of varicella zoster
      virus (VZV) infections, only tissue culture yields an isolate available for
      antiviral susceptibility testing or pathogenesis studies. However, conventional
      tube tissue culture (TC) has a low sensitivity. OBJECTIVE: To increase the
      recovery rate of VZV in tissue culture. STUDY DESIGN: Clinical specimens
      submitted for VZV isolation were processed by TC and rapid shell vial (SV)
      techniques followed by a blind passage (BP). For SV, two incubation times and two
      mAbs, directed against viral-early or immediate-early antigens, were compared.
      RESULTS: Isolation of VZV using the SV stained at 72 h postinoculation was more
      sensitive (88-96%) than TC (50-67%), or the SV technique at 48 h (66-70%). It was
      also more rapid than TC (9.6 days). The comparison of mAbs yielded similar
      results in SV. Blind passage of SV at 7 days postinoculation further increased
      detection. CONCLUSIONS: SV combined with BP is the method of choice for VZV
      isolation.

PMID- 15566863
TI  - Effects of sonication of clinical specimens on detection of cytomegalovirus in
      shell vial cultures.
AB  - BACKGROUND: The centrifugation-enhanced shell vial (SV) method of virus culturing
      has decreased the time to laboratory detection of many viruses, and has become
      the principal method for the rapid detection of cytomegalovirus (CMV) in clinical
      specimens. OBJECTIVES: To examine the use of sonication and centrifugation of
      clinical specimens as a means of optimizing the sensitivity of SV detection of
      CMV, decreasing the toxicity of specimens to the SV monolayer, and facilitating
      the examination and interpretation of SV monolayers. STUDY DESIGN: A total of 350
      clinical specimens submitted for CMV culture were processed and then divided in
      half, with one-half sonicated for 1 min in a cup-horn-equipped sonicator, and the
      other half left unsonicated. Sonicated specimens were centrifuged to recover a
      cell-free supernatant. SVs containing MRC-5 fibroblast monolayers were inoculated
      with either the unsonicated whole specimen or the cell-free supernatant, and were
      stained with monoclonal antibodies directed against the immediate-early antigen
      of CMV after 24 and 48 h of incubation. RESULTS: While no significant difference
      was observed in the overall number of specimens in which CMV was detected
      following sonication, sonication did afford a 31% increase in the number of CMV
      positive specimens detected at 24 h. A significant reduction in toxicity of all
      specimens except for blood was observed for the sonicated specimens, although
      sonication of blood increased the number of blood specimens toxic to the
      monolayer by 40%. Use of the cell-free inoculum following sonication facilitated
      microscopic examination and interpretation of SV monolayers without adversely
      affecting the sensitivity of the culture. CONCLUSIONS: Sonication of clinical
      specimens prior to shell vial culturing for CMV is beneficial and can help to
      reduce specimen toxicity, facilitate interpretation of monolayers, and allow the
      earlier detection of a positive specimen.

PMID- 15566864
TI  - Quantitation and genotyping of hepatitis C virus RNA in sera of hemodialysis and
      AIDS patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent in hemodialysis
      and AIDS patients. Little information exists about the viral load in those
      patients. OBJECTIVE: To characterize HCV infection in hemodialysis and AIDS
      patients, the viral load in the sera was measured. Results were compared with
      genotypes, gender of the patients, and biochemical markers of active hepatitis.
      STUDY DESIGN: Sera from a total of 442 patients were screened with a third
      generation EIA, and anti-HCV immunoreactivity was confirmed with the Wellcozyme
      HCV Western Blot. After qualitative PCR with the Amplicor PCR Test, positives
      were genotyped using a reverse hybridization test. Determination of HCV levels
      was done with the Amplicor HCV Monitor assay. RESULTS: HCV RNA was detected in
      the sera of 95 (74.8%) EIA-positive patients. HCV RNA levels ranged from 1 x
      10(4) to 1.4 x 10(6) molecules of HCV RNA/ml. Median HCV RNA levels of AIDS
      patients were slightly higher than those of hemodialysis patients. Male patients
      had higher median HCV RNA levels compared with female patients. No association
      between HCV RNA levels and both alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels was found. The most common genotypes were type 1b
      and type 1a, followed by type 3, type 4, and type 2a. There were no significant
      differences in HCV RNA levels among patients with genotypes 1a, 1b, and 2a.
      Patients infected with types 3 and 4, respectively, had significantly lower HCV
      RNA levels compared with other genotypes. CONCLUSION: Because the Amplicor HCV
      Monitor assay allows quantitation of low-titer viremic patients, HCV RNA levels
      were distinctly lower compared with previous reports. HCV RNA levels of males did
      not differ significantly from those of females. ALT and AST are very poor
      indicators of ongoing HCV infection. Patients with chronic type 3 or type 4 HCV
      infection tended to have lower HCV RNA levels.

PMID- 15566866
TI  - Viral diagnosis by antigen detection techniques.
AB  - BACKGROUND: Diagnosis of viral infections can be obtained in the early stages of
      a disease by detection of viral antigens directly in the clinical specimen. This
      has become an important tool for rapid virus diagnosis. METHODS: Antigens
      produced during virus infections can be detected either in cells collected from
      the site of infection by immunohistological investigation or in secretions and
      blood by solid phase immunoassays (IA). Viruses causing acute respiratory
      infections can be diagnosed in cells from the respiratory tract, viruses causing
      vesicular eruptions in epithelial cells from skin scrapings, rabies virus in
      nerve cells of the brain or epithelial cells from skin and cornea and
      cytomegalovirus (CMV) matrix antigen, pp65, can be detected in peripheral blood
      leukocytes (PBL) by immunofluorescence (IF) or immunoperoxidase techniques. The
      quality of specimens can be easily checked during the reading of results. Some
      IAs for antigen detection, such as detection of HBsAg and HIV p24 antigen in
      blood are standardized and sensitive. Others give less sensitive results because
      of the variation of quality of the clinical specimen. The latex agglutination
      tests are mainly used for rapid detection of virus or viral antigens in faeces:
      rota-and adenoviruses; the method may not be very sensitive but yields a result
      within a few minutes. Assays detecting viral nucleic acids are more sensitive
      than antigen detection tests because of a tremendous amplification of gene
      segments obtained by the polymerase chain reaction (PCR). So far such assays are
      time consuming and expensive and are mainly used in specific clinical situations.
      RESULTS: After introduction of specific monoclonal antibodies (Mabs), the antigen
      detection techniques are increasingly used. the need for quality control, trained
      staff, and standardized reagents and methods for specimen collection and
      preparation is now being appreciated. IF for viral respiratory viruses is used
      for diagnosis and epidemiological studies all over the world. Likewise, IF is
      still the method most often used for rabies diagnosis. For CMV, the pp65 matrix
      antigen is shown to be a sensitive marker closely correlated with clinical
      symptoms. Its detection by the IF technique has proven to be superior to other
      techniques for prediction of CMV pneumonia in bone marrow transplant patients.
      IAs are currently used in fully automated systems for large scale diagnosis based
      on antigen detection in serum specimens. Increase of antibody specificity on the
      solid phase by use of Mabs directed against the most abundant viral antigen in
      the clinical specimen shortens the reaction time; this has been employed in most
      of the constantly appearing new rapid diagnosis kits based on the immunoassay
      principle. CONCLUSION: Although, in virology, more sensitive results are obtained
      by the gene detection method, PCR, directly in clinical samples, viral antigen
      detection tests are, after the introduction of Mabs for diagnostic purposes,
      increasingly used because of their low demand on laboratory equipment, their
      rapid and early result and relatively low cost. Antigen detection is successfully
      used directly in clinical specimens for rapid diagnosis of many viral infections
      as well as for identification of tissue culture isolated viruses. With Mab-based
      IAs the reaction time is shortened and new rapid, almost 'instant test' kits are
      appearing on the market.

PMID- 15566868
TI  - Classical and molecular techniques for the diagnosis of viral gastroenteritis.

PMID- 15566867
TI  - Advances in the diagnosis of respiratory virus infections.
AB  - BACKGROUND: Advances have been made in selecting sensitive cell lines for
      isolation, in early detection of respiratory virus growth in cells by rapid
      culture assays, in production of monoclonal antibodies to improve many tests such
      as immunofluorescence detection of virus antigens in nasopharyngeal aspirates, in
      highly sensitive antigen detections by time-resolved fluoroimmunoassays (TR-FIAs)
      and biotin-enzyme immunoassays (BIOTH-E), and, finally, in the polymerase chain
      reaction (PCR) detection of respiratory virus DNA or RNA in clinical specimens.
      All of these advances have contributed to new or improved possibilities for the
      diagnosis of respiratory virus infections. OBJECTIVES AND STUDY DESIGN: This
      review summarizes our experiences during the last 15 years in the development of
      diagnostic tests for respiratory virus infections, and in use of these tests in
      daily diagnostic work and in epidemiological studies. RESULTS: Immunofluorescence
      tests based on monoclonal antibodies, all-monoclonal TR-FIAs, and biotin-enzyme
      immunoassays (EIAs) have about the same sensitivities and specificities. They
      compare well with the sensitivity of virus culture. PCR followed by liquid-phase
      hybridization is a sensitive method for detecting adenovirus DNA and enterovirus
      and rhinovirus RNA in clinical specimens. IgG EIA on paired acute and
      convalescent phase sera is the most sensitive serological test for respiratory
      virus infections and is a valuable reference method when evaluating the
      sensitivity of new diagnostic tests. The IgG avidity test can distinguish primary
      infections from re-infections at least in respiratory syncytial virus (RSV)
      infections. IgM antibody assays, on the other hand, had low sensitivities in our
      studies. CONCLUSIONS: The choice of diagnostic methods for respiratory virus
      infections depends on the type and location of the laboratory, the number of
      specimens tested, and the previous experience of the laboratory. Virus culture,
      whenever possible, should be the basic diagnostic method; the results, including
      identification of the virus, should be available no more than 24 h later than the
      results of rapid diagnostic tests. In small laboratories, especially in hospitals
      where specimen transportation is well organized, immunofluorescence may be the
      best choice for antigen detection with the provision that an experienced
      microscopist and a good UV microscope are available. If the laboratory receives a
      large number of specimens and has previous experience with EIAs, then biotin-EIAs
      or TR-FIAs may be the most practical techniques. Their advantages include the
      stability of the antigens in clinical samples since intact, exfoliated epithelial
      cells are not required, treatment of specimens is practical, testing of large
      numbers of specimens is possible, and reading the printed test result is less
      subjective than reading fluorescence microscopy. The larger role of PCR in the
      diagnosis of respiratory virus infections depends on future developments such as
      practical methods to extract DNA or RNA and to purify the extracts from
      nonspecific inhibitors, plus further improvements to minimize cross
      contamination. Group-specific detection of enteroviruses and rhinoviruses is an
      example of the potential for PCR technology. In experienced laboratories. EIA IgG
      antibody tests should be available. Recombinant antigens may be a useful part of
      such assays.

PMID- 15566869
TI  - Uses of biosensor technology in the development of probes for viral diagnosis.
AB  - BACKGROUND: Since 1990, a new biosensor technology based on surface plasmon
      resonance makes it possible to visualize molecular recognition as a function of
      time, in terms of change in mass concentration occurring on a sensor chip
      surface. One of the reactants is immobilized on a dextran matrix while the other
      is introduced in a flow passing over the surface. The binding is followed in real
      time by the increase in refractive index caused by the mass of bound species.
      OBJECTIVES: In the present review, the applications of this new technology for
      developing probes intended for viral diagnosis will be described. STUDY DESIGN:
      In contrast with other immunoassay systems, the biosensor technique preserves the
      conformational integrity of the reactants since no labelling is required. It also
      makes it possible to follow every step of a multiple-layer assay and allows
      interaction measurements in real time. Suitable antigen and antibody probes can
      be selected on the basis of the conditions of the diagnostic assay that is being
      developed, especially in terms of affinity and specificity. RESULTS: Our results
      suggest that when the cyclic peptide 209-222 of the E1 protein of hepatitis C
      virus (HCV) is immobilized on the sensor chip via a biotin moiety, it retains a
      constrained conformation which is better recognized by HCV antibodies than the
      linear form. Data are presented which indicate that the biosensor technique
      facilitates the screening and selection of anti HIV-1 antibodies that are likely
      to possess the most potent neutralizing potential. CONCLUSION: Since there is a
      good correlation between BIAcore and ELISA data, it seems likely that the
      biosensor technology will be increasingly used for developing reagents intended
      for viral diagnosis.

PMID- 15566870
TI  - Laboratory diagnosis of intrauterine and perinatal virus infections.
AB  - BACKGROUND: Intrauterine infection with rubella, cytomegalovirus (CMV), varicella
      zoster virus (VZV), parvovirus B19 and human immunodeficiency virus type 1 (HIV
      1) may occur following maternal infection. Diagnosis of congenital infection in
      the neonate is dependent on the appropriate laboratory techniques being used.
      Prenatal diagnosis of intrauterine infection may also be indicated. Herpes
      simplex virus (HSV), HIV-1, VZV, enteroviruses, hepatitis B (HBV) and hepatitis C
      viruses (HCV), human T-cell lymphotropic viruses (HTLV-1 and 2) and genital
      papillomaviruses (PVs) may be acquired at delivery. Neonatal HSV, VZV and
      enterovirus infections may be severe or even fatal. Perinatally acquired HBV,
      HCV, HIV-1 and HTLVs are associated with persistent infection and chronic disease
      in later life. However, if the mother is identified as a carrier in the antenatal
      period, mother-infant transmission of HBV may be prevented by active/passive
      immunisation of the neonate, HIV-1 by caesarian section or antiviral therapy, and
      of HTLV-1 by avoiding breast feeding. OBJECTIVES AND STUDY DESIGN: To review the
      techniques available for the diagnosis of intrauterine infections, neonatal
      infections with HSV, HIV-1, VZV and enteroviruses, maternal infection with HBV,
      HCV and HIV-1 and prenatal diagnosis of intrauterine rubella, CMV and B19.
      RESULTS: Congenital rubella may be diagnosed by detection of specific IgM, but
      virus detection is the technique of choice for congenital cytomegalovirus.
      Congenital VZV may be diagnosed by serological techniques in up to 71% of cases.
      Detection of virus in vesicle scrapings or swabs from the oropharynx is the
      technique of choice for neonatal HSV, while enterovirus infections are best
      diagnosed by detection of viral RNA. A clinical diagnosis of congenital VZV is
      often possible. HIV-1 may be diagnosed within 3 months of birth by testing serial
      blood samples with a combination of techniques. Maternal infection with HBV, HCV,
      HIV and HTLV1/11 may be diagnosed by serological techniques and genital PVs by
      detection of viral DNA. Chorionic villus samples, amniotic fluid and fetal blood
      may be obtained for prenatal diagnosis of infection. Although detection of virus
      in amniotic fluid is the technique of choice for prenatal diagnosis of CMV,
      insufficient data is currently available to determine whether it may be used for
      intrauterine rubella. The most reliable technique for diagnosis of fetal B19
      infection is detection of viral DNA in fetal blood. CONCLUSIONS: Close liaison
      between clinicians and microbiologists/virologists is required in order that
      appropriate specimens are collected from infant and/or mother and appropriate
      tests conducted. The use of TORCH screening should be discouraged.

PMID- 15566871
TI  - Antibody tests: progress and pitfalls.
AB  - BACKGROUND: Serological tests are the basis for most laboratory virological
      diagnosis. The recent development of DNA amplification methods, allowing the
      detection of viral nucleotide sequences in clinical specimens, raises the
      question of whether or not these will supersede antibody tests. OBJECTIVE: To
      assess the current strengths and weaknesses of current viral serology in the
      light of this new diagnostic approach. STUDY DESIGN: Review of relevant
      literature and consideration of experience in a national reference laboratory.
      RESULTS: Due to technical advances, the intervals between exposure and
      seroconversion have decreased and tests for the specificity of antibody screening
      assays have improved. Also, viral antibodies can now be detected in saliva and
      urine. For epidemiological purposes sera can be tested cheaply and accurately in
      small pools. In some cases infecting viruses can be subtyped according to the
      antibody response. On the negative side, increased sensitivity has made tests
      prone to cross-contamination effects and, in some circumstances, serological
      responses are delayed or absent. CONCLUSION: Viral diagnosis using antibody tests
      is highly cost-effective. Because they are versatile, relatively accurate and
      cheap, these tests will remain the backbone of routine laboratory diagnosis for
      some time to come.

PMID- 15566872
TI  - Licencing of diagnostic HIV kits-to keep a sensible standpoint in an area of
      permanent revolution.
AB  - BACKGROUND: In vitro diagnostic medical devices or 'test kits' are important
      tools for diagnosing illnesses and monitoring the patients' state of health or
      the effects of medical treatment. It is in the public interest that commercial
      kits are of high quality. OBJECTIVES: To review the current situation of kit
      evaluation in Europe and to establish practical and sensible criteria for kit
      evaluation in general, based on the Swiss experience with the licencing of kits
      for the detection of human immunodeficiency virus (HIV) infection. Kit evaluation
      should provide the user with a selection of sufficiently good products. In
      addition, it should be simple and not require rare patient materials. Also of
      importance is that all manufacturers are treated equally. METHODS: The evaluation
      criteria depend on the legal situation, the intended use of the test, the state
      of the art and the graveness of false-negative or -positive results. In addition
      to diagnostic sensitivity and specificity, other important considerations include
      the quality control by the manufacturer, kit presentation, intra- and inter-lot
      reproducibility and how a test fits into a country's adopted testing system.
      RESULTS: The above goals can be achieved by setting minimal performance
      standards, preferably in the form of a lower limit of the confidence interval for
      the sensitivity/specificity that has been observed in the test's field
      evaluation. The better the test, the fewer samples have to be studied. For tests
      with no false results observed during field trials, the minimum sample number
      necessary for demonstration of a sensitivity or specificity >/= 99% is about 400,
      while it is 700 for a >/= 99.5% demonstration. Further insight into sensitivity
      is provided by results from well described and frequently used commercial
      seroconversion panels. This represents a dynamic tool that readily identifies
      insensitive kits that have become technically obsolete. Specificity assessment
      should not only involve blood donors, but also appropriate clinical controls. It
      is clear that the test design has an important bearing with respect to
      sensitivity and specificity. There are inherent advantages and disadvantages of
      indirect binding assays, capture assays and double antigen sandwich assays.
      Positive or negative results with these different test formats may not carry
      exactly the same message. CONCLUSION: Efficient kit evaluation does not require
      tens of thousands of samples but can be performed with relatively little
      disbursement on materials and manpower.

PMID- 15566873
TI  - Evaluation of diagnostic kits and reagents-a viewpoint from the industry.
AB  - BACKGROUND AND OBJECTIVES: Assuring the performance characteristics of in vitro
      diagnostics (IVDs) is a major objective of product evaluations. This includes
      using sets of well planned and controlled trials in order to: (i) analyze product
      performance characteristics; (ii) validate design specifications; and (iii)
      assess product safety. Performance parameters like sensitivity, specificity,
      precision, robustness etc. are assessed in order to assure that the product
      design consistently meets performance specifications upon manufacturing.
      Documentation on product performance can also be used for pre-market approval
      submissions which are required in some European countries. THE CONTEXT FOR IVD
      PRODUCT EVALUATIONS: Internal quality policies have the following impact on the
      design of evaluation trials: (i) use of at least three production lots (with
      final specifications); (ii) performed under field conditions and GLP; (iii)
      performed at different sites; (iv) analyzing clinical specimens having
      statistically significant numbers; (v) use of validated statistical
      methods/software (SAS); (6) quality-assuring documentation. External expectations
      influencing product evaluations include the following aspects: (i) state-of-the
      art performance; (ii) technical standards like ISO, EN, DIN; (iii) Customers'
      needs; and (iv) regulatory requirements for the approval of IVDs. IVD PRODUCT
      EVALUATIONS AT ABBOTT DIAGNOSTICS: Based on a quality system (ISO 9001), product
      evaluations are a major constituent in a phased development and manufacturing
      process of IVDs prior to market entry. Product evaluations address particular
      performance goals which relate to aspects outlined above including regulatory
      requirements. Depending on the assay type, they are displayed in absolute and
      relative features, e.g. (i) intra- and interassay variation below 10% for
      precision; (ii) no false-negatives among certified positive specimens for
      sensitivity; (iii) a 'true' specificity > 99.75% (lower limit of 95% CI); and (4)
      earlier detection of seroconversion by the 'new' assay vs. the 'old' assay etc.
      The basic design and the assessment of performance characteristics is described
      by giving particular examples.

PMID- 15566874
TI  - Molecular in situ localization techniques in diagnosis and pathogenicity studies
      of enteroviral heart disease.
AB  - BACKGROUND: Enteroviruses, including coxsackieviruses of group B (CVB), are
      considered to be the most common agents of viral myocarditis. As demonstrated by
      in situ hybridization for the detection of viral RNA in endomyocardial biopsies
      and autopsy hearts, such infections are also detectable in patients with
      'idiopathic' dilated cardiomyopathy, indicating the possibility of myocardial
      enterovirus persistence. Persistent enterovirus infection of the human heart is
      supported by the recent discovery in various murine models of chronic
      myocarditis, demonstrating that CVB3, typically a cytolytic virus, is capable of
      evading immunological surveillance in a host-dependent manner. METHODS: In order
      to investigate mechanisms underlying acute and persistent enterovirus infection
      in the myocardium, diverse tissues from CVB3 infected immunocompetent mice were
      processed in in situ hybridization for the detection of viral RNA. In addition,
      virus-host interactions were analyzed at the subcellular level in the myocardium
      in the course of the infection by means of an electron microscopic in situ
      hybridization assay. RESULTS: A close spatial and temporal relationship between
      viral replication and inflammatory lesions was observed during the acute as well
      as persistent phase of myocardial infection. A multiorgan study revealed that, in
      addition to heart muscle cells, lymphoid cells of spleen and lymph nodes are
      persistently infected. The results obtained at the ultrastructural level
      demonstrate that loss of host cell integrity is a direct consequence of acute
      viral replication and confirm that chronic myocarditis may be associated with
      persistent heart muscle infection. CONCLUSIONS: Viral replication plays a central
      role in the pathogenesis of acute and chronic myocarditis. Immune cells are
      important targets of the infection and provide a non-cardiac viral reservoir.

PMID- 15566875
TI  - Artificial mosaic proteins as new immunodiagnostic reagents: the hepatitis E
      virus experience.
AB  - BACKGROUND: Naturally occurring viral proteins derived from cell culture and
      recombinant proteins expressed in procaryotic systems have been used extensively
      as target proteins in the development of immunoassay methods for the detection of
      antibodies. However, immunoassays utilizing these proteins often yield false
      positive reactions suggesting that it may be possible to identify and remove
      regions responsible for these non-specific reactions. OBJECTIVE: In this paper we
      describe a new strategy for the construction of immunoreactive recombinant
      proteins designed to improve immunoassay specificity. STUDY DESIGN: A synthetic
      gene encoding an artificial polypeptide composed of antigenic epitopes of the
      hepatitis E virus (HEV) proteins was constructed from short oligonucleotides by
      the polymerase chain reaction (PCR). The polypeptide comprises a mosaic of three
      antigenically dominant regions from the protein encoded by open reading frame 2
      (ORF2), one antigenically active region from the protein encoded by ORF3 of the
      Burmese HEV strain, and one antigenically active region from the protein encoded
      by ORF3 of the Mexican strain. The mosaic protein was expressed in Escherichia
      coli as a chimera with glutathione-S-transferase or beta-galactosidase. RESULTS:
      Guinea pig sera containing antibodies to the corresponding HEV synthetic peptides
      were used to demonstrate by immunoblot analysis and by enzyme immunoassay (EIA)
      the presence and accessibility of all HEV-specific antigenic epitopes designed
      into the mosaic protein. Both hybrid proteins were shown by immunoblot analysis
      using a panel of human anti-HEV-positive and -negative sera to be HEV-specific. A
      sensitive and specific EIA was developed to detect IgG anti-HEV activity in human
      sera. A neutralization test using individual synthetic peptides corresponding to
      the epitopes designed into the mosaic protein was also developed to confirm IgG
      anti-HEV activity by absorbing the specimen before retesting by EIA. CONCLUSION:
      An artificial mosaic protein composed of short linear HEV-specific antigenic
      epitopes was constructed from synthetic oligonucleotides by PCR and used to
      develop a sensitive and specific EIA for the detection of anti-HEV activity in
      human sera.

PMID- 15566876
TI  - Diagnosis of human cytomegalovirus infections in the immunocompromised host.
AB  - BACKGROUND: In the last decade several major advances have been made in the rapid
      diagnosis of human cytomegalovirus (HCMV) infections and disease in
      immunocompromised patients both at the immunological and molecular level.
      OBJECTIVES: The objective was to review in some detail the new diagnostic tools
      allowing determination and quantitation of HCMV infection in blood of
      transplanted and AIDS patients. STUDY DESIGN: The determination and quantitation
      as well as the clinical significance of antigenemia, viremia, HCMV-infected
      circulating endothelial cells (CEC) and DNAemia will be discussed in view of the
      therapeutic management of HCMV disease. Levels of viremia represent the number of
      p72-positive cultured fibroblasts inoculated with 2 x 10(5)PBL, while levels of
      antigenemia represent number of pp65-positive PBL/2 x 10(5) PBL examined. The
      number of CEC is determined simultaneously and in parallel with antigenemia.
      DNAemia, both qualitative and quantitative, can be determined by polymerase chain
      reaction (PCR) per 1 x 10(5)PBL. The clinical utility of determining either
      immediate-early or late mRNA is still debated. RESULTS: In solid organ transplant
      recipients mean levels of viremia of 100 and of antigenemia of 400 correlate with
      onset of clinical symptoms. The time between first HCMV positivity and the onset
      of symptoms (>/= 10 days), together with the observation that most patients with
      reactivated infection clear virus without treatment, allowed the establishment of
      an antigenemia cut-off of 100 for the initiation of treatment. On the other hand,
      seronegative recipients of solid organs from seropositive donors must be treated
      preemptively, i.e. at first appearance of HCMV positivity in blood. Due to the
      risk of early appearance of HCMV pneumonia, the same preemptive approach must be
      used in bone-marrow transplant recipients. In acquired immunodeficiency syndrome
      (AIDS) patients with HCMV infection/disease, general criteria for initiation of
      treatment are more difficult to establish and treatment must be maintained. CEC
      are detected only in untreated disseminated HCMV infections with organ
      involvement. Qualitative DNA determination is useful only in special cases, such
      as in aqueous or vitreous humor of AIDS patients with HCMV retinitis.
      Quantitative DNA levels obtained by PCR are much more helpful for diagnosing HCMV
      disease and establishing initiation of treatment. CONCLUSIONS: New diagnostic
      procedures currently ensure fine monitoring of HCMV infections/diseases and
      evaluation of the effect of specific antiviral treatment in the immunocompromised
      host.

PMID- 15566877
TI  - Current issues in the diagnosis of hepatitis B and C virus infections.
AB  - Diagnostic tests for hepatitis B virus infection are well established, although
      development of format and components continues. Variants of HBV with amino acid
      changes in the major antigenic determinant of the surface protein (HBsAg), and
      which may escape neutralisation by anti-HBs, have been described in many
      countries. The increasing reliance on monoclonal antibodies in the formulation of
      new assays for HBsAg raises the question of whether these surface variants may
      escape detection. The prevalence of variants which are unable to synthesise the e
      antigen (precor mutants), especially in certain geographical areas, means that
      the absence of HBeAg in carriers, with or without anti-HBe, does not necessarily
      indicate clearance of viraemia. The discovery of hepatitis C virus was followed
      rapidly by evidence of considerable sequence variation among different isolates.
      At least six major genotypes of HCV are recognised worldwide. Nonetheless,
      current assays seem reliable for detection of antibodies to this diverse virus.
      Assays for antigen are not available and diagnosis of viraemia requires sensitive
      detection of the viral genome, for example using reverse transcription and the
      polymerase chain reaction (RT-PCR). Evaluation of the efficacy of anti-viral
      therapy requires quantitative assays, adding a further degree of complexity.
      Other tests, such as the branch DNA (bDNA) assays are available, but lack
      sensitivity. Whether different genotypes of HCV vary in their pathogenicity and
      response to therapy remains contentious and convenient methods for determination
      of the genotype (or equivalent serotyping assays) are required to resolve this
      issue.

PMID- 15566878
TI  - The year of Pasteur: from the concept of antibody and antigen by Bordet (1895) to
      the ELISA. What future for immunological diagnosis?
AB  - BACKGROUND: Chronological account of the increase of the sensitivity of
      immunological reactions and future possible improvements are presented. RESULTS:
      During these 100 years, the sensitivity of immunological reactions has been
      increased by approximately 5 log by reference to the basic technique of
      quantitative immunoprecipitation. OBJECTIVES: Future progresses can be foreseen
      (i) in the signal of labeled reagents, with the development of time-resolved
      fluoro-immunoassays; (ii) in the presentation of viral antigens on solid phase,
      with a larger use of polystyrene microbeads; (iii) in the antigen used for
      antibody detection, by promoting the characterization of antibodies to
      conformational structures of viruses; (iv) for antibody reagent preparations,
      particularly by immunomodulation for the development of antibodies to weak
      epitopes or to presently non-immunogenic structures and; (v) in the
      discrimination of detected antibodies. Characterization of the discontinuous or
      continuous nature of the recognized epitopes and of the affinity of antibodies
      could permit to date the infection. Inhibition of a monoclonal antibody reacting
      with a conformational epitope, and identification of an idiotope, will be more
      selective than the usual characterization of a large polyclonal antibody
      activity. Finally, the use of antibodies specific of the sole SIgA, molecule is
      expected to carry new informations in serological diagnosis at the entry of
      numerous infectious agents. ELISA techniques will become tightly complementary to
      PCR, which leads to an early diagnosis when the focus of infection is easily
      accessible, but rapidly looses its diagnosis capacity in acute infections.

PMID- 15566879
TI  - Isolation of an in vitro transmissible agent with reverse transcriptase activity
      from a blood donor with a borderline-positive HIV-1 serology for more than five
      years.
AB  - BACKGROUND: Reverse transcriptase (RT) is present in all infectious retrovirus
      particles. Sensitive RT tests should thus detect all such particles. A family of
      ultrasensitive RT tests, product-enhanced reverse transcriptase (PERT) assays,
      have been designed. Accumulated results show that (i) a first version of the PERT
      assay that uses microtiter/ELISA technology detects RT of only 3-11 retroviral
      particles, (ii) very different human and animal lenti- and oncoviruses are
      detected very sensitively, (iii) HIV-1 is detected as sensitively as with
      polymerase chain reaction (PCR) for viral RNA, and (iv) prevalence of elevated
      particle-associated RT in plasma of unselected Swiss blood donors was 1.9%.
      OBJECTIVE: To investigate whether the RT activity detected in one unselected
      donor with a chronically elevated level of the liver enzyme alanine
      aminotransferase and two selected donors with chronically indeterminate or
      borderline-positive HIV-1 serology was due to human immunodeficiency virus (HIV)
      or human T-cell leukemia virus (HTLV) infection. STUDY DESIGN: Blood samples were
      tested by PCR for viral DNA and/or RNA of HIV-1, HIV-2, HTLV-1, HTLV-2, hepatitis
      B and C virus. Serological tests and virus cultures were also employed. RESULTS:
      Infection with any of the above agents could not be demonstrated. Virus
      cultivation in one case of borderline-positive HIV-1 Western blot for more than 5
      years yielded a peak of RT production that was repeatedly transmissible to fresh
      cells. CONCLUSIONS: The findings suggest the presence of an infectious RT
      positive agent, probably different from HIV-1/2 or HTLV-1/2, in a healthy
      individual with chronically borderline-positive HIV-1 serology. The PERT assay
      may detect retroviruses currently undetectable by other tests. The use of more
      stringent Western blot interpretation guidelines other than those of CDC or WHO
      is strongly recommended.

PMID- 15566880
TI  - HIV-1 D subtype viruses in Finland.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-1 strains are divided into seven
      genetic subtypes based on their gag sequences (A, B, C, D, F, G and H). Strains
      that have appeared in Finland show unusual heterogeneity compared to most
      industrialized countries, up to 25% of the strains belong to non-B subtypes
      (Liitsola et al., 1996). Three D subtype viruses have so far been identified in
      Finland. All patients were men, one Kenyan immigrant and two Finnish men, who had
      been infected in Africa. Here we describe some of the characteristics of the
      genomic diversity of these strains. METHOD: The genotype was determined by direct
      solid-phase sequencing of the p7 gag region. Phylogenetic analysis was done using
      standard methods. RESULTS: The analysis showed that the D subtype sequences
      clustered clearly distinctly from the other non-B strains, but did not suggest
      any transmission links between the three cases. From one case both cerebrospinal
      fluid (CSF) and blood leukocyte virus isolates were studied. The analysis
      revealed significant differences between the blood and CSF viruses. A four amino
      acid duplication and other differences were observed between the strains.
      CONCLUSION: The results confirm that D subtype viruses do indeed occur in Finland
      and they represent quite heterogenic strains within the D cluster.

PMID- 15566881
TI  - Sequence analysis of the 5' non coding region of Turkish HCV isolates:
      implications for PCR diagnosis.
AB  - Hepatitis C virus (HCV) is a positive-strand RNA virus related to pestiviruses
      and flaviviruses. The 5' noncoding region (NCR) of the virus genome consists of
      324-341 nucleotides and is generally highly conserved among different HCV
      isolates which has made this region the choice for primer selection in
      amplification of HCV sequences by polymerase chain reaction (PCR). In this study,
      we report the partial nucleotide sequences of the 5'-NCR from type 1a (n = 4),
      type 1b (n = 6) and type 4 (n = 1) Turkish HCV isolates. Sequence information was
      obtained by direct sequencing of RT-PCR product using biotinylated primers and
      single strands were sequenced using T7 DNA polymerase after binding to
      streptavidin coated magnetic beads. In comparison to prototype type 1a consensus
      sequence, all type 1b sequences had A-G substitution at position - 99. Nucleotid
      changes from the prototype 1a sequence were found in 12 of the 174 nucleotide
      positions. The most variable domain spans 51 nucleotides (positions - 167 to -
      117) where nine polymorphic sites were identified. Although the nucleotide
      sequence of the 5'-noncoding region is highly conserved there are type-specific
      polymorphic sites within this region that has to be taken into consideration in
      the design of oligonucleotide primers for reliable amplification of sequences
      from different HCV genotypes.

PMID- 15566882
TI  - Detection of human papillomavirus type 16 in microtitre plate based immuno
      enzymatic assays: use to determine E5 gene expression in cervical carcinomas.
AB  - BACKGROUND: E5-based nested polymerase chain reaction (PCR) assays and a PCR
      enzyme immunoassay (EIA) to detect human papillomavirus type 16 (HPV-16) DNA have
      been developed. These assays were designed to detect small amounts of HPV-16 DNA
      for epidemiological studies of subclinical infection. OBJECTIVES: The E5 gene of
      HPV-16 may be lost in some cell lines derived from cervical carcinomas. The aim
      of this study was to determine if, and how frequently, E5 gene loss occurs in
      biopsy samples from patients with cervical lesions. STUDY DESIGN: Sixteen HPV-16
      (E7) DNA positive and five HPV-16 DNA negative cervical lesions (nineteen
      cervical carcinomas, two cervical intraepithelial neoplasias) were investigated
      by E5 nested PCR and EIA. RESULTS: Overall, 15 of the 16 (93.75%) HPV-16 E7
      positive samples were positive for HPV-16 E5 DNA: 14 of 16 (87.5%) were positive
      by E5 PCR and 15 of 16 (93.75%) were positive by E5 PCR, nested PCR and by PCR
      EIA. One of 14 HPV-16 (E7) DNA positive cervical carcinomas was negative for E5
      DNA in all three assays. CONCLUSION: Loss of the HPV-16 E5 open reading frame
      (ORF) is a rare event in HPV-16 positive cervical carcinomas and was detected in
      just one of 14 (7.1%) cases.

PMID- 15566883
TI  - DNA insitu hybridization in the diagnosis of human papillomavirus infection.
AB  - BACKGROUND: Certain types of human papillomavirus (HPV) are shown to be
      associated with the development of genital lesions. DNA hybridization methods are
      used for the diagnosis of HPV infections. OBJECTIVE: To use a nonradioactive DNA
      in situ hybridization system for the investigation of HPV infections responsible
      for the development of genital lesions in women. STUDY DESIGN: Sections from
      archival paraffin embedded biopsy specimens of 59 cases were screened for the
      presence of HPV DNA sequences by using digoxigenin labeled DNA probe which is
      specific for all types of HPVs and digoxigenin detection system. The study group
      consisted of samples diagnosed as squamous hyperplasia of the vulva (group 1),
      koilocytosis (group 2), condyloma acuminatum/koilocytotic atypy (group 3),
      cervical intraepithelial neoplasia (CIN), and epidermoid carcinoma (group 4).
      RESULTS: No HPV DNA was detected in groups 1 and 2 which consisted of 3 and 13
      specimens respectively. Seven of 11 (63.6%) specimens in group 3 and 7 of 32
      (21.9%) in group 4 were found to be positive for in situ HPV DNA. Seven positive
      samples in group 3 and one positive sample in group 4 were typed as HPV 6/11.
      Five samples of the remaining positives in group 4 were typed as HPV 16/18. One
      case was found to be positive with both 16/18 and 31/33. CONCLUSION:
      Nonradioactive DNA in situ hybridization is an easy and efficient method to be
      performed for the diagnosis of HPV infections. Koilocytosis with atypy is
      directly correlated with HPV infection and it is suggested to monitor the CIN
      cases with HPV type 16/18 infection since the pathology can be progressive.

PMID- 15566884
TI  - Specific IgE detected by ELISA and immunoblot after human cytomegalovirus
      infection (HCMV) in renal transplant (RT) recipients.
AB  - BACKGROUND: Specific HCMV IgE response has been reported by some authors, and was
      proposed as a valuable virologic marker of CMV infection. OBJECTIVES: we
      evaluated specific HCMV IgE in renal transplant patients with active (primary and
      secondary) HCMV infection with special interest to symptomatic infections. STUDY
      DESIGN: Specific IgE was tested retrospectively by ELISA and immunoblot (IB) on
      sera of 55 RT patients who were followed before and after transplantation with
      virologic markers of CMV infection. RESULTS: Total serum IgE levels were similar
      in control group and in patients with primary and secondary HCMV infections. Anti
      CMV specific IgE response by ELISA was more frequently found in patients with
      primary infection (76.9%) than in patients with secondary infection (47.1%).
      These specific IgE reacted on immunoblot with a 150 kDa protein in 84.6% of
      patients with primary infection and 94.1% with secondary infections; and reacted
      with rp52 (pUL44) in 76.9% of primary infection and 47.1% of secondary infection.
      CONCLUSIONS: Anti-CMV specific IgE tested by immunoblot and ELISA is a marker of
      CMV infection. It was clearly detected in cases of active infection (primary and
      secondary) and was present in cases with severe CMV clinical manifestations. In
      contrast, anti-CMV specific IgE, was consistently negative among healthy blood
      donors. This is the first report of CMV proteins detected by IgE immunoblot.

PMID- 15566885
TI  - Virus-induced interferon production in leukocyte cultures from children with
      recurrent respiratory infections. A follow-up study.
AB  - BACKGROUND: Lowered yields of virus-induced interferon (IFN) by leukocyte
      cultures were previously suggested to be associated with recurrent respiratory
      infections in children (Pitkaranta et al. (1993) Clin. Diagn. Virol. 1, 101-108).
      OBJECTIVES: To investigate if the observed lowered IFN producing capacity was
      secondary to the underlying disease and, consequently, would be normalized after
      recovery of the child from the chain of infections. STUDY DESIGN: Forty-eight 3
      12-year-old children suffering from recurrent upper respiratory tract infections
      (acute otitis media included) were followed-up for 2 years. Their clinical
      condition and virus-induced interferon production in cultures of peripheral blood
      leukocytes were examined at the beginning and end of this period. RESULTS: In 24
      children the health improved strikingly during the follow-up, in 12 children a
      mild improvement took place, while 12 children remained constantly ill. IFN
      yields in cultures stimulated with corona- and respiratory syncytial viruses
      improved along with the clinical situation of the children. Parallel cultures
      induced with adeno-, influenza A or rhinoviruses did not show a similar
      correlation. CONCLUSION: These results suggest that the relationship between
      interferon production by leukocyte cultures and recurrent infections is complex
      and may be virus-specific.

PMID- 15566886
TI  - The clinical usefulness of a Puumalavirus recombinant nucleocapsid protein based
      enzyme-linked immunosorbent assay in the diagnosis of nephropathia epidemica as
      compared with an immunofluorescence assay.
AB  - BACKGROUND: Nephropathia epidemica (NE), a hemorrhagic fever with renal syndrome
      (HFRS) predominantly encountered in northern Europe, is a febrile disease,
      commonly associated with acute renal impairment. A rapid and reliable serological
      diagnosis is required to differentiate NE from other acute febrile illnesses in
      endemic areas. OBJECTIVE: To evaluate a Puumala (PUU) virus recombinant
      nucleocapsid protein (rN) based enzyme-linked immunosorbent assay (ELISA) for the
      serological diagnosis of NE as compared with an immunofluorescence assay (IFA) in
      a clinically relevant patient sample. STUDY DESIGN: During a four-month period,
      618 serum samples from 512 patients with an illness suggestive of NE, sent to the
      Department of Clinical Virology for serological analysis, were included in the
      study. All sera were tested by PUU rN ELISA for presence of specific IgG, IgM and
      IgA antibodies and by IFA using PUU virus infected cells as antigen for presence
      of IgG and IgM antibodies. Patients with discordant results by IFA and rN ELISA
      were further serologically and/or clinically evaluated to assess the probability
      of NE. RESULTS: Compared to IFA, the specificities of the IgM and IgG rN ELISA
      were 100% and the corresponding sensitivities were 94.0%. The positive and
      negative predictive values of the PUU IgM rN ELISA in diagnosing NE infection was
      100 and 98.6%, respectively. The positive predictive values for present NE
      infection of IgG rN ELISA and IFA were 68.3 and 71.4%, respectively. The positive
      predictive value of IgA rN ELISA was 95.8% and the negative 92.7%. CONCLUSIONS:
      The demonstration of specific IgM by rN ELISA is a highly specific and reliable
      method for the serological confirmation of NE. Detection of IgG antibodies by rN
      ELISA or IFA has a low predictive value to diagnose NE in an endemic area. The
      diagnostic value of IgA determination is in between IgM and IgG determinations.

PMID- 15566887
TI  - Diagnosis of congenital cytomegalovirus infection by detection of viral DNA in
      dried blood spots.
AB  - BACKGROUND: The reference method of cytomegalovirus (CMV) isolation from urine or
      saliva is not a feasible routine technique for all newborns, and laboratory
      diagnosis of this infection would be useful both for epidemiological purposes and
      to enable prompt institution of adequate measures to identify and correct late
      sequelae. Extraction and amplification of viral DNA from dried blood spots (DBS)
      collected from babies in the first days of life during routine screening for
      genetic and metabolic disorders has been proposed for the early diagnosis of
      viral congenital infections. OBJECTIVES: To test the method for CMV DNA
      extraction from DBS and to evaluate the results obtained in newborns with and
      without a diagnosis of congenital infection based on viral isolation from urine
      and or saliva at birth. STUDY DESIGN: DBS from Guthrie cards collected in babies
      who underwent virological tests for CMV infection were tested for CMV DNA by
      observers blinded to the virological results. DNA was extracted from DBS both in
      water and in cell culture medium according to Shibata et al. with minor
      modifications. The products of nested polymerase chain reactions (PCR) amplifying
      two regions in the IE1 and gp58 genes were detected by agarose gel
      electrophoresis. Strict control measures were adopted to avoid carryovers and
      contaminations. RESULTS: DBS from the eight symptomatic and 11 asymptomatic
      congenitally infected babies were positive when extraction was performed in
      medium, whereas extraction in water failed to identify two of the asymptomatic
      cases. The results obtained with the two extraction methods agreed in the
      remaining cases; the 71 CMV negative control babies were negative and two out of
      21 cases of supposed postnatal infection were diagnosed as congenital on the
      basis of a positive DBS. All positive cases were identified by gp58 PCR but only
      slightly over half of them by IE1 PCR. Extraction in medium was more efficient
      than in water. CONCLUSIONS: The method of CMV DNA extraction in medium followed
      by amplification of the gp58 region showed 100% sensitivity and specificity
      compared with isolation in cell culture. Therefore, we propose this procedure to
      diagnose congenital CMV infection at birth and also later.

PMID- 15566888
TI  - Detection of herpes simplex virus (types 1 and 2) and human herpesvirus 6 DNA in
      human brain tissue by polymerase chain reaction.
AB  - BACKGROUND: Previous studies, using a variety of techniques to determine whether
      herpes simplex virus type 1 (HSV-1) and/or type 2 (HSV-2) are present in normal
      brains or have a higher incidence in either multiple sclerosis (MS) or
      psychiatric disorders have yielded conflicting results. Similarly, studies to
      examine human brain tissue for human herpes virus 6 (HHV-6) have also proved
      inconsistent. These discrepancies may be partially due to differences in
      sensitivity of the methods used. OBJECTIVES: To determine whether: (i)
      Herpesvirus latency is a normal occurrence in the human central nervous system
      (CNS), (ii) the incidence of latency is higher in either demyelinating diseases
      or schizophrenia (iii) significant virus reactivation occurs in demyelinating
      diseases. STUDY DESIGN: Frozen brain tissue from 7 cases of MS/demyelinating
      disease, 6 cases of schizophrenia and 27 non-neurological and 3 neurological
      controls were examined by polymerase chain reaction (PCR) for the presence of HSV
      1 DNA. Tissue from the above catagories (except schizophrenia) were also examined
      for HSV-2 and HHV-6 DNA. In situ hybridization (ISH) and immunocytochemistry
      (ICC) were carried out in formalin-fixed paraffin sections from selected HSV PCR
      positive cases, including a case of HSV encephalitis (HSE). RESULTS: Cases from
      all groups were found to be positive for HSV-1 by PCR. Only one case (MS) was
      found positive for HSV-2, whereas HHV-6 DNA was present in 18 of 23 brains (MS
      and controls). Only the HSE case gave positive results with ISH and ICC
      techniques. CONCLUSIONS: These results suggest that herpesvirus latency in the
      human CNS is a common occurrence but there is no obvious correlation with
      increased incidence in either demyelinating disease or schizophrenia.
      Furthermore, failure to detect virus by ISH or ICC (except in a case of HSE)
      indicates lack of any significant virus reactivation in demyelinating diseases.

PMID- 15566889
TI  - IgG subclass response to human parvovirus B19 infection.
AB  - BACKGROUND: IgG antibodies are essential to immunity against human parvovirus B19
      and can neutralize infection both in bone marrow cell cultures infected in vitro
      and in chronically infected immunosuppressed individuals. OBJECTIVES: To assess
      the levels and response kinetics of IgG subclasses towards individual structural
      proteins of human parvovirus B19. STUDY DESIGN: Subclasses of IgG for capsid
      proteins VP1 or VP2 were quantified by EIA using monoclonal antibodies in 30
      acutely infected and 30 convalescent patients, as well as in 32 remotely infected
      and 20 non-infected controls. RESULTS: In all groups of seropositive individuals
      the predominant subclass for either structural protein was IgG1. Subclass IgG3
      was associated with acute infection. By contrast, IgG4 appeared months after
      infection, and occurred specifically towards VP1. The ratio of VP1-specific
      subclasses IgG3 and IgG4 provided a diagnostic test for recent infection with a
      specificity of 98% and a sensitivity of 97%. CONCLUSIONS: Comparative measurement
      of VP1-specific IgG3 and IgG4 is useful in diagnosis. The IgG4 results point to
      long-term expression of immunologically active VP1 and to T-cell help of T(h)2
      type for B-cells recognizing VP1.

PMID- 15566890
TI  - Diagnosis of cytomegalovirus (CMV) infection in pediatric transplant patients by
      the antigenemia, shell vial, and conventional culture assays performed on blood:
      correlation with CMV disease.
AB  - BACKGROUND: Human cytomegalovirus (CMV) is a significant cause of morbidity and
      mortality in transplant recipients. Isolation of CMV from blood leukocytes (CMV
      viremia) is considered predictive of CMV disease in transplant recipients.
      Therefore, investigation of methods for the rapid detection of CMV in the blood
      is important for diagnosis and management of these patients. OBJECTIVE: To
      compare three techniques for the diagnosis and monitoring of CMV infection in a
      pediatric transplant population through the quantitative detection of CMV in
      peripheral blood leukocytes (PBL). METHODS: Serial blood specimens were obtained
      for most patients. After separation of the PBL from each specimen, aliquots of
      the PBL were used for direct detection of CMV antigenemia by immunoperoxidase
      staining of acetone-fixed cells (CMV-vue kit, INCSTAR), and by immunofluorescence
      staining of formaldehyde-fixed cells (Complete 1C3 kit, Biosoft Argene). PBL were
      also inoculated into conventional cell culture tubes and shell vials. Patients'
      medical records were reviewed to ascertain the clinical significance of the
      results. RESULTS: A total of 154 specimens obtained from 38 pediatric transplant
      recipients were evaluated. CMV was detected in 16 specimens obtained from eight
      patients: 11 specimens were found positive with the CMV-vue kit, 10 with the
      Complete 1C3 kit, four by conventional culture, and one by the shell vial assay.
      Seven of the eight patients with CMV-positive PBL had clinical signs and other
      laboratory evidence of active CMV infection. In general, a high-level antigenemia
      was demonstrated in the presence of clinical disease, but there were exceptions.
      CONCLUSIONS: The two antigenemia kits were more sensitive than conventional
      culture and the shell vial assay for the detection of CMV in the blood of
      pediatric transplant patients. Our results suggest that CMV antigenemia is a
      sensitive and specific rapid method for the diagnosis and monitoring of CMV
      infection in our patient population.

PMID- 15566891
TI  - Recent influenza B viruses in Europe: a phylogenetic analysis.
AB  - BACKGROUND: Influenza B virus evolution is currently in a unique situation having
      two cocirculating main lineages B/Yamagata/16/88 (YM/88)-like and B/Victoria/2/87
      (VI/87)-like viruses. Continuation of this bifurcation would mean development
      towards distinct forms resembling the HA subtypes of influenza A viruses.
      OBJECTIVE: We wanted to examine both intraepidemic heterogeneity and recent
      evolution in these two lineages. The initial purpose was to determine the
      geographic distribution of the two sublineages of the VI/87-like viruses in
      Europe in 1989-1990 under circumstances of low epidemic activity. Due to the
      outbreaks of YM/88-like viruses since 1991, the study was extended to contain the
      evolution of these viruses and their genetic relationship with the vaccine
      strains of that time. STUDY DESIGN: The HA1 gene sequences of 33 influenza B
      strains isolated in ten European countries since 1989 were determined and
      compared with those available through databases or personal contacts. RESULTS:
      The two main lineages, YM/88-like and VI/87-like viruses, both continued to
      circulate. In both lineages, changes in the potential glycosylation sites were
      observed. Two sublineages of the VI/87 lineage cocirculated during the 1989-1990
      season with somewhat different geographic distributions. A high degree of
      intraepidemic heterogeneity was observed, as well as examples of conserved
      nucleotide sequences. CONCLUSIONS: It is important to follow the evolution and
      circulation of VI/87-like viruses. Current vaccines give poor or no protection
      against VI/87-like viruses in immunologically unprimed children or even in primed
      adults (Levandowski et al., 1991, Pyhala et al., 1994). Changes in the potential
      glycosylation pattern in the latest virus isolates of both main lineages have
      occurred and it is interesting to see the significance of these changes to viral
      evolution.

PMID- 15566892
TI  - Populations with high prevalence of antibody against hepatitis E virus in Israel.

PMID- 15566893
TI  - Seroprevalence of viral hepatitis in Inner Mongolia, China.

PMID- 15566894
TI  - Importance of simultaneous active cytomegalovirus and Epstein-Barr virus
      infection in renal transplantation.
AB  - BACKGROUND: Although being the most common infective complication after
      transplantation, cytomegalovirus (CMV) infection does not always produce disease
      symptoms in immunosuppressed patients. Development of CMV disease may depend on
      different factors such as virulence of particular CMV strains and impairment of
      CMV-specific immune reactions. OBJECTIVE: Demonstration of the importance of
      simultaneous Epstein-Barr virus (EBV) activation for development of symptomatic
      CMV infections. STUDY DESIGN: 208 renal transplantation patients were monitored
      for 3 years with respect to (i) CMV and EBV replications, and (ii) clinical
      symptoms associated with combined and single infections, respectively. RESULTS:
      CMV and EBV replications were observed in 22% and 19% of the patients,
      respectively. Many of these active virus infections were found to overlap in time
      (59% and 74% of all active CMV and EBV infections, respectively). The increased
      detection of combined CMV and EBV infections probably does not result from higher
      initial immunosuppression in these patients, since the percentage of patients
      receiving OKT3 or ATG was almost identical in the groups of single and combined
      infections. In 18 cases of combined infections, CMV replication preceeded EBV
      replication, while EBV replication prior to CMV replication was observed in one
      case only, indicating that activation of latent EBV infection may be induced
      during active CMV infection. CONCLUSIONS: Simultaneous replication of both
      viruses seems to be clinically important, since severe clinical symptoms were
      observed only in the group of combined CMV and EBV infections. Symptoms were
      similar to the clinical pictures of CMV disease. Thus, simultaneous EBV
      replication may be an important co-factor for the development of CMV disease,
      possibly by further decreasing the number of functional CD4 T cells or enhancing
      the CD8-positive cytolytic/suppressor T-cell subset as reflected by the
      comparatively stronger decrease of CD4/CD8 ratio during simultaneous CMV and EBV
      replication, particularly in the case of symptomatic infections.

PMID- 15566895
TI  - Viruses that multiply in the gut and cause endemic and epidemic gastroenteritis.
AB  - BACKGROUND: Acute infectious diarrhea in young children is a leading cause of
      morbidity and mortality in developing countries. Even in developed countries,
      infectious enteritis is second only to respiratory infections as a cause of
      morbidity in early childhood. OBJECTIVE: To nominate the various viral agents
      that cause enteritis, discuss the pathogenesis, clinical features, epidemiology
      and diagnostic procedures employed. STUDY DESIGN: Pertinent literature was
      reviewed and the findings of investigations carried out on viral enteritis by
      various colleagues recalled. RESULTS: The viruses causing gastroenteritis
      include: Rotaviruses; Adenoviruses-especially Ad 31, Ad 40 and Ad 41; members of
      the Caliciviridae, e.g. Norwalk virus, Hawaii virus, Snow Mountain virus, Taunton
      virus, Southampton virus, Toronto virus (formerly mini-reovirus) and others;
      Astrovirus; Coronavirus; Torovirus; Cytomegalovirus (CMV) and possibly
      Picobirnavirus. Enteritis-producing viruses replicate in columar epithelial cells
      in the distal parts of villi of the small intestine. Two mechanisms are addressed
      to explain why diarrhea occurs. Clinically, the main expression of illness is a
      watery diarrhea that lasts 24 h to about 7 days. Vomiting is of shorter duration
      and may not always accompany the diarrhea. Fever is generally 38.5 degrees C.
      Virus is shed in the stool for about 3-7 days. Diagnostic procedures employ
      electron microscopy (EM), immune electron microscopy (IEM), enzyme-linked
      immunosorbent assay (ELISA), time-resolved fluoroimmunoassay (TR-FIA), latex
      agglutination, polyacrylamide gel electrophoresis (PAGE) and the polymerase chain
      reaction (PCR). CONCLUSION: In developed countries viral enteritis among young
      children may be up to three times more common than bacterial gut disease. With
      the exception of CMV enteric involvement, the stool is characteristically not
      bloody and white blood cells are not found. Patient management may involve the
      employment of IV replacement therapy to counter dehydration and electrolyte
      imbalance. Milder cases may be managed with oral rehydration.

PMID- 15566896
TI  - Sensitivity and specificity of a DNA polymerase chain reaction nonisotopic-based
      detection method for the confirmation of infection with human T-lymphotropic
      virus types I and II.
AB  - BACKGROUND: A convenient, standard format for the detection of polymerase chain
      reaction (PCR) amplicons would increase the use of PCR for the confirmation of
      infection with human T-lymphotropic virus types I and II (HTLV-I and HTLV-II).
      OBJECTIVES: To determine the sensitivity and specificity of an enzyme
      oligonucleotide assay (EOA) for the confirmation of infection with HTLV-I or HTLV
      II. STUDY DESIGN: The sensitivity of the EOA was determined by examining 88
      specimens representing diverse geographic-associated genotypes and clinical
      manifestations. The specificity was determined by testing 40 HTLV
      seroindeterminate (PCR-negative) specimens. RESULTS: Of the 52 HTLV-I-positive
      specimens tested, 46 (88%) were confirmed positive for HTLV-I by the EOA; these
      included 25 of 30 (83%) specimens from asymptomatic carriers, 14 of 15 (93%)
      specimens from patients with HTLV-I-associated myelopathy, and all 7 specimens
      from patients with adult T-cell leukemia. Similarly, 33 of 36 (92%) HTLV-II
      positive specimens were confirmed positive for HTLV-II. None of the specimens
      were wrongly classified. All specimens tested with distinct geographic-associated
      genotypes for HTLV-I and -II were detected by EOA. Analysis of seroindeterminate
      specimens, all of which were previously shown to be negative by nested PCR,
      showed that none of 40 were detected by either the HTLV-I or HTLV-II EOA.
      CONCLUSIONS: The overall sensitivity of the EOA detection for confirmation of
      HTLV-I and HTLV-II was 79 of 88 (90%) and the overall specificity was 100%. These
      findings demonstrate that the EOA provides a simple, standardized assay system
      for reliable confirmation and typing of HTLV infection.

PMID- 15566897
TI  - Acute HIV seroconversion illness presenting as African viral haemorrhagic fever.
AB  - BACKGROUND: Both human immunodeficiency virus type 1 (HIV-1) and African viral
      haemorrhagic fever (VHF) viruses cause similar symptoms in acutely infected
      individuals and must be included in the differential diagnosis in areas where HIV
      1 and VHF viruses both occur. OBJECTIVES: To determine the cause of an acute
      illness in a patient at risk of exposure to both HIV-1 and African VHF viruses.
      RESULTS: Serological examination revealed the presence of high levels of the p24
      core antigen of HIV-1 in the absence of antibodies to HIV-1 in a specimen
      collected during the acute stage of the infection. On follow-up, the antigen
      enzyme-linked immunosorbent assay (ELISA) became negative while the antibody
      ELISA and confirmatory Western blot for HIV-1 became positive. CONCLUSIONS: Acute
      HIV seroconversion illness may have protean manifestations and, in the more
      severe forms, may cause diagnostic dilemmas, particularly in regions where
      African VHFs occur.

PMID- 15566898
TI  - Analyses of functional antibody responses in HIV-1-infected individuals after
      vaccination with rgp160.
AB  - BACKGROUND: The immune response to HIV infection has been extensively studied and
      the antibody response against the virus has been characterized in detail. It is,
      however, still unclear which immune function it is most important to stimulate
      when administering a vaccine against HIV. OBJECTIVES: To analyze the functional
      antibody responses in asymptomatic HIV-1-infected individuals after vaccination
      with rgp160. STUDY DESIGN: Forty-nine asymptomatic HIV-1-infected individuals
      were followed for 9 months and analyzed for changes in functional antibody
      responses. Forty of them received HIV-1 envelope rgp160 injections and nine did
      not. RESULTS: Increased levels of antibodies mediating neutralization and
      cellular cytotoxicity (ADCC) could be seen in subjects who also showed a better
      CD4 development compared with the patients without increased levels of functional
      antibodies. Out of nine matched HIV-infected and influenza-immunized controls,
      none had increased neutralizing activity and only one had an increased ADCC
      titer. An increased capacity to block soluble CD4 binding to gp120 occurred in 10
      immunized patients. Seroreactivity and avidity maturation were detectable to
      peptides representing consensus HIV-1 envelope regions, indicating an anamnestic
      response to the patients own virus. CONCLUSIONS: The humoral immune response in
      HIV-1-infected individuals was moderately influenced by repeated gp160
      immunizations, while previous studies have shown that HIV-specific T-cell
      reactivity was strongly increased.

PMID- 15566899
TI  - Inhibition of syncytia-inducing (SI) virus by autologous serum from HIV-1
      infected individuals.
AB  - BACKGROUND: Progression from HIV infection to AIDS is often accompanied or even
      predicted by a switch of the virus to a more pathogenic or syncytia-inducing (SI)
      phenotype concomitant with the development of HIV variants escaping neutralizing
      antibodies. OBJECTIVE: Here we studied the capacity of sera to neutralize
      autologous SI-HIV or the laboratory strain III(B) and compared these data to the
      viral load in HIV-1-infected patients. METHODS: The SI phenotype of HIV was
      detected by co-cultivation of peripheral blood mononuclear cells (PBMCs) with MT2
      cells in 112 patients stratified by their CD4 cell counts. Sera at dilutions of 1
      : 15 and 1 : 75 were added to MT2 co-cultures with autologous PBMCs as well as
      with HIV-1/IIIB-infected H9 cells to study the inhibitory capacity. The p24
      antigenemia was detected by enzyme-linked immunosorbent assay (ELISA) and the
      circulating HIV RNA was determined using the polymerase chain reaction (PCR).
      RESULTS: The SI virus was detected in PBMCs from 31/65 patients with < or = 200
      CD4+ cells, 8/28 patients with 201-499 CD4+ cells, and 1/19 patients with > or =
      500 CD4+ cells. Sera from 16/40 patients inhibited the autologous SI-HIV. In sera
      from patients with < or = 200 CD4+ cells, p24 antigen could be detected in 17/34
      (50%) patients with non-syncytia-inducing (NSI) phenotype and in 7/19 (37%)
      patients carrying SI-HIV without serum inhibition. In contrast, all 12 sera with
      inhibitory activity to the autologous SI-HIV were negative for p24 antigen. A
      similar tendency was seen in patients with higher CD4+ T-cell counts. The mean
      load of circulating HIV RNA did not differ among groups of patients.
      Independently of their neutralizing activity to the autologous SI virus, the
      majority of sera were able to neutralize the laboratory HIV-1/III(B).
      CONCLUSIONS: While most of the patients' sera neutralized the laboratory HIV
      1/III(B) strain, only some sera were able to inhibit the autologous SI-HIV. In
      these cases, the detectable SI-HIV may still be controlled by the immune system
      in vivo, which is consistent with a low p24 antigenemia.

PMID- 15566900
TI  - Diagnosis of hepatitis C virus (HCV) infection by antigen-capturing ELISA.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major cause of non-A non-B hepatitis.
      Detection of circulating antibodies against HCV by enzyme-linked immunosorbent
      assay (ELISA) has provided the main approach for the diagnosis of HCV infection.
      Most ELISA kits use a mixture of core, NS3, NS4 and NS5 antigen as capture
      antigens and enzyme-labeled goat anti-human IgG as conjugate. OBJECTIVES: To
      establish an ELISA system based on the antigen-capturing principle, using a
      recombinant chimeric polyprotein containing four HCV antigenic components as
      antigen. STUDY DESIGN: HCV antigens were expressed in Escherichia coli as
      chimeric polyprotein either in inclusion bodies or in soluble form. Protein
      expressed in inclusion bodies was used as solid-phase antigen, and the antigen
      expressed in a soluble form was used as enzyme conjugate after being labeled with
      horseradish peroxidase (HRP). RESULTS: Genes coding HCV antigens were cloned and
      sequenced, chimeric polyproteins containing four immunodominant components (core,
      NS3, NS4 and NS5) were expressed in E. coli both in soluble and in inclusion body
      form. These two chimeric proteins retained the antigenicity of HCV antigens.
      Antibody-capturing ELISA using the chimeric antigens showed a sensitivity of 97%
      (97/100) and a specificity of 98% (97/99) using the reference panel from the
      National Institute for the Control of Pharmaceutic and Biological Products of
      China (NICPBC); the same assay showed a sensitivity of 97.9% (48/49) and a
      specificity of 100% (43/43) using the self-established reference panel. Antigen
      capturing ELISA was set up using the antigen labeled with horseradish peroxidase
      as conjugate, and was shown to be as sensitive as (97.9%) and more specific than
      (100%) antibody-capturing ELISA using the reference panel in this work. The
      antigen-capturing ELISA also showed a high accordance (98.9%) with UBI HCV enzyme
      immunoassay (EIA) 4.0 kits (United Biomedical Inc. USA). CONCLUSION: Antigen
      capturing ELISA provided a convenient, sensitive and more specific approach for
      the diagnosis of hepatitis C virus infection.

PMID- 15566901
TI  - Detection of respiratory viruses in nasopharyngeal secretions with
      immunofluorescence technique for multiplex screening-an evaluation of the
      Chemicon assay.
AB  - BACKGROUND: Antigen detection with immunofluorescence is an efficient method for
      diagnosis of respiratory tract infections, but has previously not allowed for
      simple screening of many respiratory viruses. Pools of monoclonal antibodies
      against various respiratory viruses are now available, and are potentially
      important tools for improvement of antigen detection in nasopharyngeal samples.
      OBJECTIVE: To evaluate the commercially available Chemicon immunofluorescence
      assay (IFA; respiratory viruses panel and identification kit), an indirect IFA
      containing a pool of monoclonal antibodies for screening for influenza A, B,
      respiratory syncytial virus (RSV), parainfluenza 1, 2, 3 and adenovirus, and the
      respective individual antibodies. STUDY DESIGN: Ninety-six frozen preparations
      from nasopharyngeal secretions or bronchoalveolar lavages were retrospectively
      examined with the assay, and the results compared with other IFAs for antigen
      detection and cell culture isolation obtained in the everyday routine.
      Nasopharyngeal preparations from 300 children with lower respiratory tract
      infections at Beijing Children's Hospital during the 1994-1995 winter season were
      also examined. RESULTS: The sensitivity of the Chemicon assay compared to the
      combined results of routine IFA and isolation was 89% and specificity 92%. If
      five identifications of RSV made with the Chemicon assay alone were regarded to
      be truly positive, the specificity was 100%. A viral etiology was identified in
      105/280 (38%) evaluable samples drawn from the Chinese children (influenza A 20%,
      RSV 14%, adenovirus 3% and parainfluenza 1, 2 or 3, 7%). CONCLUSION: One problem
      with the Chemicon assay was that for around 4-13% of samples there was a non
      specific staining in the screening assay, necessitating stainings for
      verification. Despite this, the assay is an excellent tool for identification of
      viral respiratory tract infections, giving an increased sensitivity compared to
      direct immunofluorescence assays.

PMID- 15566902
TI  - HBsAg confirmation: an experimental test.
AB  - BACKGROUND: The specificity of HBsAg testing is to be confirmed with antibody
      blocking to avoid false positive results. OBJECTIVE: To test the experimental
      HrAb HBsAg-blocking activity and to use this new antibody in the verification of
      repeatedly reactive HBsAg blood serum samples. STUDY DESIGN: HbsAg screening of
      three quality control panels was followed by a comparative confirmatory test with
      commercial HuAb and experimental HrAb. The HrAb was used in subsequent HBsAg
      confirmation trials. RESULTS: A good agreement in the results obtained using the
      two antibodies was found, independently of the type of HBsAg neutralization step
      performed (either preincubation or competitive inhibition). Of the 97 repeatedly
      reactive HBsAg blood serum samples, 79 were 'confirmed positives'. On repeated
      confirmations by two antibodies, 13/18 'not confirmed' converted to 'confirmed
      positives', while the same five samples still remained false positive.
      CONCLUSION: The results suggest that (1) HrAb is as good as HuAb in HBsAg
      confirmation and (2) HBsAg confirmatory testing is essential in the laboratory
      examinations of the HBsAg repeatedly reactive samples.

PMID- 15566903
TI  - Rapid, non-radioactive detection of virus infection by polymerase chain reaction.
AB  - BACKGROUND: Polymerase chain reaction (PCR) diagnosis of infectious diseases,
      especially virus diseases, offers a very sensitive and specific technique for
      clinical diagnosis. However, detection systems for amplified DNA requiring
      radioactive probe hybridization or signal development using blot transfer or
      nucleotide capture require overnight incubation or specially labeled probe
      molecules for analysis of amplified DNA. OBJECTIVES: To place this technology in
      the clinical laboratory, rapid and sensitive methods are needed for the detection
      of amplified DNA which are applicable to the assay of multiple specimens
      representing many different organisms and requiring a minimum of manipulation.
      STUDY DESIGN: Electrophoretic separation of amplified DNA fragments, stained with
      the fluorescent dye SYBR Green I, and laser scanning of the gels for detection of
      virus-specific PCR products was compared with detection of amplified DNA by
      liquid hybridization with radioactive probes and gel retardation analysis of
      labeled probe molecules. RESULTS: Fluorescent scanning methodology was applied to
      the detection of cytomegalovirus (CMV), herpes simplex virus (HSV) and the human
      immunodeficiency virus (HIV). This method was at least 10 times more sensitive
      than radioactive probe hybridization in the detection of CMV-specific PCR
      products. This method also required less time and avoided the use of
      radioactivity. CONCLUSIONS: Clinical diagnosis of virus infections can be
      conveniently and rapidly accomplished, while avoiding the dangers of radioactive
      probe handling, by fluorescence staining and laser scanning of specifically
      amplified gene fragments. This technology is applicable to the detection of genes
      from many different organisms, without specially synthesized and/or labeled
      oligonucleotide primer or probe sequences.

PMID- 15566904
TI  - Effect of statin therapy prior to elective percutaneous coronary intervention on
      frequency of periprocedural myocardial injury.
AB  - This study evaluated whether pretreatment with statins was associated with a
      decreased incidence of periprocedural myocardial injury. Periprocedural
      myocardial injury occurs after percutaneous coronary intervention (PCI) and is
      associated with adverse outcomes. The pleiotropic properties of statins stabilize
      plaque and decrease the inflammatory milieu of atherosclerotic lesions.
      Accordingly, we hypothesized that preprocedural statin therapy would decrease
      periprocedural myocardial injury. We enrolled 425 patients who underwent
      successful PCI. The control arm (n = 150) included patients not on statin therapy
      at the time of PCI, and the statin arm (n = 275) included patients who were
      taking statin medication before PCI. All patients had serial enzymes measured,
      including creatine kinase (CK), CK-MB, and troponin I. The incidence of increased
      levels of CK and CK-MB >3 times normal and the absolute increase in CK and
      troponin I were compared between groups. The control arm had significantly higher
      periprocedural levels of CK. In the control group, 6% of patients had CK
      increases >3 times the upper limit of normal compared with 1.8% in the statin
      group (p = 0.02). The control arm had a higher frequency of CK-MB increases >3
      times the upper limit of normal (7.3% vs 2.2%, p = 0.01). There was a trend
      toward higher levels of troponin I in the control group (3.21 vs 1.85 ng/ml, p =
      0.06). Thus, statin therapy before elective PCI was associated with lower levels
      of periprocedural CK.

PMID- 15566905
TI  - Comparison of safety and efficacy of the early injection of atropine during
      dobutamine stress echocardiography with the conventional protocol.
AB  - Although dobutamine-atropine stress echocardiography (DASE) is an established
      method for evaluating patients who have coronary artery disease (CAD), it can
      increase test duration and a patient's exposure to large doses of dobutamine. New
      protocols, including the early injection of atropine during dobutamine stress
      echocardiography (EA-DSE), have been proposed to decrease test duration. This
      study compared the safety, efficacy, and accuracy of EA-DSE with those of DASE.
      We retrospectively evaluated 3,163 patients who underwent DASE and 1,664 patients
      who underwent EA-DSE over a period of 12 years. In EA-DSE, atropine at a dose
      </=2 mg was started with 20 microg/kg/min of dobutamine if heart rate was <100
      beats/min. Diagnostic accuracy for detecting CAD (>50% stenosis) was assessed in
      patients who underwent quantitative angiography </=3 months of stress testing.
      The dobutamine dose used in EA-DSE was smaller than that used in DASE (31 +/- 6
      vs 36 +/- 6 microg/kg/min, p <0.0001), although the atropine dose was larger (0.8
      +/- 0.5 vs 0.5 +/- 0.25 mg, p <0.0001). EA-DSE resulted in a significantly
      shorter duration of dobutamine infusion (12.4 +/- 2.0 vs 14.6 +/- 2.5 minutes, p
      <0.0001), more diagnostic studies (88% vs 81%, p <0.0001), and a lower incidence
      of minor adverse effects than did DASE. The rate of major adverse effects was
      similar in the 2 protocols. Sensitivities, specificities, positive predictive
      values, negative predictive values, and accuracies for detecting CAD were 84%,
      90%, 93%, 76%, and 86% for EA-DSE and 86%, 78%, 84%, 79%, and 82% for DASE,
      respectively (p = NS). Therefore, EA-DSE is a safe and effective alternative to
      DASE and had a similar accuracy for the detection of CAD.

PMID- 15566906
TI  - A 25-year perspective into the changing landscape of patients hospitalized with
      acute myocardial infarction (the Worcester Heart Attack Study).
AB  - Over the past several decades, significant advances have been made in the primary
      and secondary prevention of coronary artery disease. However, effects of changing
      lifestyle and treatment practices on demographic and clinical profiles and on
      hospital outcomes of patients who present with acute myocardial infarction (AMI)
      have not been well characterized. We carried out a prospective population-based
      investigation of >25-year trends (1975 to 2001) in demographic and clinical
      characteristics, treatment practices, and hospital outcomes of patients who had
      been hospitalized with AMI. Residents of a metropolitan area (Worcester,
      Massachusetts) who had been hospitalized with validated AMI (n = 10,440) in all
      greater Worcester hospitals during thirteen 1-year periods between 1975 and 2001
      comprised the sample of interest. Patients who had been hospitalized during the
      most recent study years were significantly older, were more likely to be women,
      and had a greater prevalence of co-morbidities. Hospitalized patients were
      increasingly more likely to receive effective cardiac medications and coronary
      interventions over the period under investigation. Multivariable-adjusted
      hospital survival rates improved considerably over time, whereas different trends
      were observed in the occurrence of several important clinical complications. The
      present results provide insights into the changing characteristics of patients
      who are hospitalized with AMI, treatment practices, and their short-term
      outcomes. Given the magnitude of AMI and evolving approaches to manage it,
      continued monitoring of these trends remains of considerable clinical and public
      health importance.

PMID- 15566907
TI  - Outcome of patients with newly diagnosed atrial fibrillation at the Mayo Clinic
      and residing in that area.
AB  - This study examined the prognostic significance of atrial fibrillation (AF) in a
      community-based cohort. AF, the most common cardiac dysrhythmia, frequently
      occurs in the presence of concomitant medical illness. Population-based studies
      have associated AF with excess mortality, and this risk of death is independent
      of concomitant cardiovascular disease. The effect of noncardiovascular medical
      illnesses on mortality in patients who have AF has not been determined. We
      examined a community-based cohort of 390 residents of Olmsted County, Minnesota,
      who had newly diagnosed AF; patients were identified retrospectively but followed
      prospectively. The cohort included all patients who had electrocardiographically
      proved first-onset AF; patients were not excluded on the basis of medical
      illness. Mean age of the cohort was 73 +/- 14 years (56% were men). Mean follow
      up was 2.7 +/- 1.7 years. Onset of AF frequently occurred during hospitalization
      (78%). One hundred sixty-six deaths occurred, a death rate significantly higher
      than expected for the cohort. Most deaths had a noncardiovascular cause. This
      trend was maintained for patients who had no previous cardiovascular disease and
      for those who had a cardiovascular diagnosis at the time AF was diagnosed. AF is
      observed frequently among hospitalized patients who are medically ill. The
      survival rate of these patients is low, but AF may be only a minor component of
      the excess mortality.

PMID- 15566908
TI  - Comparison of the prognostic value of left ventricular hypertrophy in African
      American men versus women.
AB  - Echocardiographically determined left ventricular (LV) hypertrophy may be a
      stronger risk factor of cardiovascular disease (CVD) for women than for men,
      although it is unclear whether reported gender differences are real or
      attributable to confounding. We evaluated echocardiographic LV hypertrophy
      (defined as LV mass/height(2.7) >/=51 g/m(2.7)) collected from the African
      American population of the Atherosclerosis Risk in Communities Study. Incident
      CVD events (57 in men, 62 in women) were determined during a median follow-up of
      4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial
      infarction, cardiac death, coronary revascularization, and stroke. We conducted 2
      analyses. First, we created matched samples of 340 men and 812 women who had LV
      hypertrophy based on propensity score and estimated the gender-specific incidence
      rate ratios and population-attributable risks. Second, we evaluated the complete
      cohort (604 men and 1,113 women) with Poisson's regression after adjusting for
      age, body mass index, hypertension, diabetes mellitus, ratio of total cholesterol
      to high-density lipoprotein cholesterol, current smoking, and education level. LV
      hypertrophy was significantly predictive of incident CVD, and the association
      shown by analyses of matched propensity scores was similar in men and women
      (incidence rate ratio 1.88 vs 1.92, p = 0.97 for men, population-attributable
      risk 0.22 vs 0.26, p <0.07 for women). In the multivariate analysis, we found
      comparable effect estimates for LV hypertrophy (incidence rate ratio 1.66 vs
      2.09, p = 0.55 for men; population-attributable risk 0.24 vs 0.32, p <0.07 for
      women). Thus, LV hypertrophy is a strong predictor of CVD in African-Americans,
      and the effect of LV hypertrophy on CVD is similar in men and women.

PMID- 15566909
TI  - Three-dimensional assessment of left ventricular systolic strain in patients with
      type 2 diabetes mellitus, diastolic dysfunction, and normal ejection fraction.
AB  - Left ventricular (LV) diastolic dysfunction often occurs in patients with type 2
      diabetes mellitus (DM) independent of atherosclerotic coronary artery disease,
      myocardial ischemia, and regional wall motion anomalies. Limited information
      exists on LV myocardial tissue strain in this patient group. We measured 3
      dimensional (3-D) parameters of LV systolic and diastolic functions in 28
      patients who had type 2 DM (age 33 to 70 years), standard echocardiographic
      evidence of LV diastolic dysfunction, and normal LV ejection fraction, and 31
      normal control subjects (age 19 to 74 years) who had no evidence of cardiac
      disease, with multislice cine anatomic and tagged magnetic resonance imaging.
      Three-dimensional analysis of the resulting images showed that peak systolic
      mitral valve plane displacement was 12% smaller (p = 0.040) and peak diastolic
      mitral valve plane velocity was 21% lower (p = 0.008) in patients who had DM than
      in normal controls. Peak systolic circumferential and longitudinal strains and
      principal 3-D shortening strain were 14%, 22%, and 10% smaller, respectively, in
      the DM group (p <0.001 for each). Peak diastolic rate of relaxation of
      circumferential and longitudinal strains and principal 3-D shortening strain were
      35%, 32%, and 33% lower, respectively, in the DM group (p <0.001 for each). Thus,
      LV systolic circumferential, longitudinal and 3-D principal strains, and
      diastolic strain rates are impaired in patients who have type 2 DM, LV diastolic
      dysfunction, and normal LV ejection fraction.

PMID- 15566910
TI  - Mechanisms of aortic valve calcification.
AB  - The calcified aortic valve lesion develops in the setting of endothelial injury
      and inflammation and displays hallmarks of atherosclerosis, including lipids
      accumulation, matrix metalloproteinase activation, and interaction with renin
      angiotensin system. Current evidence indicates that modification of
      atherosclerotic risk factors will slow the progression of aortic valve
      calcification, and valve risk factors should be addressed in all patients who
      have aortic valve calcification.

PMID- 15566911
TI  - Frequency of returning to work one and six months following percutaneous coronary
      intervention for acute myocardial infarction.
AB  - We conducted an analysis of the frequency and variables associated with early
      (after 1 month) and late (after 6 months) return to work after percutaneous
      coronary intervention for acute myocardial infarction in patients who had been
      randomized in the Stent Primary Angioplasty in Myocardial Infarction trial. Of
      450 patients who were employed before the acute myocardial infarction, 230 (51%)
      returned to work within 1 month with no increases in in-hospital and 1- or 6
      month event rates compared with those who did not return to work. Multivariate
      analysis showed that predictors of early return to work were employment in the
      United States, no history of smoking, and single-vessel coronary disease. At 6
      months, 353 of 435 patients (78%) had returned to work, and multivariate analysis
      showed that predictors of late return to work were employment in the United
      States and absence of angina.

PMID- 15566912
TI  - Association of platelet count with residual thrombus in the myocardial infarct
      related coronary artery among patients treated with fibrinolytic therapy for ST
      segment elevation acute myocardial infarction.
AB  - A higher platelet count is independently associated with the presence of residual
      thrombus in the infarct-related artery after administration of fibrinolytic
      therapy, even after multivariate adjustment.

PMID- 15566913
TI  - Soluble fibrin, C-reactive protein, fibrinogen, factor VII, antithrombin,
      proteins C and S, tissue factor, D-dimer, and prothrombin fragment 1 + 2 in men
      with acute myocardial infarction </=45 years of age.
AB  - To evaluate the contribution of hematologic factors and long-term inflammation to
      the development of myocardial infarction at a young age, we measured hematologic
      variables, including soluble fibrin and high-sensitivity C-reactive protein, in
      90 patients who had myocardial infarction and 138 controls </=45 years of age.
      Plasma levels of soluble fibrin and C-reactive protein were significantly higher
      in patients than in controls. On multivariate regression analysis, soluble fibrin
      was the strongest predictor of myocardial infarction at a young age.

PMID- 15566914
TI  - Comparison of late (four years) functional health status between percutaneous
      transluminal angioplasty intervention and off-pump left internal mammary artery
      bypass grafting for isolated high-grade narrowing of the proximal left anterior
      descending coronary artery.
AB  - In a 4-year follow-up study, we compared functional health status (FHS) in
      patients randomized to surgery (n = 51) or angioplasty (n = 51) for an isolated
      narrowing of the proximal left anterior descending coronary artery. FHS was
      assessed with the Short Form-36 and the Minnesota Living with Heart Failure
      questionnaires. Although the occurrence of angina (p = 0.036) and major adverse
      cardiac and cerebrovascular events (p = 0.02) was significantly higher 4 years
      after angioplasty, FHS did not differ between treatments and was comparable to a
      healthy reference population.

PMID- 15566915
TI  - Effect of bivalirudin on length of stay in the recovery area after percutaneous
      coronary intervention compared with heparin alone, heparin + abciximab, or
      heparin + eptifibatide.
AB  - Three hundred nine patients were followed during their recovery area stay after
      percutaneous coronary intervention. Recovery area times for patients who received
      bivalirudin during percutaneous coronary intervention showed an average reduction
      in total recovery area length of stay of 36 minutes (p <0.0001) compared with
      patients who received heparin alone. This reduction was also seen when compared
      with the heparin + abciximab group (46-minute reduction, p = 0.0007), and the
      heparin + eptifibatide group (35-minute reduction, p = 0.0005). Patients who
      received bivalirudin took significantly less time for the activated clotting time
      (ACT) to normalize despite significantly higher average ACTs and significantly
      fewer subtherapeutic ACTs.

PMID- 15566916
TI  - Endothelial dysfunction and inflammation after percutaneous coronary
      intervention.
AB  - We studied 30 consecutive patients who underwent coronary stenting with respect
      to postprocedure endothelial dysfunction and levels of pre- and postprocedure
      cytokines. Patients with severe impairment of flow-mediated dependent dilation,
      but not flow- mediated independent dilation, had higher concentrations of C
      reactive protein before percutaneous coronary intervention (12.9 +/- 20.2 vs 5.6
      +/- 13.0 microg/ml, p = 0.04) and 24 hours after stenting (18.8 +/- 20.8 vs 11.8
      +/- 20.0 microg/ml, p = 0.05) than patients without severe abnormities of
      systemic endothelial function. Thus, endothelium-dependent dilation abnormalities
      were related to the systemic inflammatory state, whereas endothelium-independent
      dilation abnormalities were not related to the inflammatory status of the
      patient.

PMID- 15566917
TI  - Impact of fluid balance on incidence of atrial fibrillation after cardiothoracic
      surgery.
AB  - Excessive fluid administration after cardiothoracic surgery has been proposed as
      a cause of postoperative atrial fibrillation. In this study, we observed that
      fluid balance and volume administered on postoperative day 2 was greater in
      patients who developed postoperative AF than in those who did not. We also found
      that net fluid balance on postoperative day 2 was an independent predictor of
      postoperative AF among patients not receiving prophylactic therapy.

PMID- 15566918
TI  - Effect of azithromycin therapy on coronary circulation in patients with coronary
      artery disease.
AB  - This study examined the effect of azithromycin therapy on the coronary
      microcirculation using measurement of coronary flow velocity reserve (CFVR) by
      transthoracic Doppler echocardiography in 35 patients with coronary artery
      disease. CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs
      3.5 +/- 0.7, p <0.001). The changes in CFVR were negatively correlated with
      changes in high-sensitivity C-reactive protein levels in patients receiving
      azithromycin.

PMID- 15566919
TI  - Stent implantation in very small coronary arteries: the Tsunami SV International
      Registry.
AB  - The aim of this multicenter registry was to examine the in-hospital and long-term
      clinical outcomes of patients who underwent Tsunami SV stent implantation for the
      treatment of lesions involving coronary arteries with a reference diameter of
      <2.5 mm. The angiographic success rate was 97.5%. No in-hospital or 30-day major
      adverse cardiac events occurred. During the 6-month follow-up, there was 1
      cardiac death (1%), and 5 subjects (4.8%) underwent repeat target lesion
      revascularization.

PMID- 15566920
TI  - Frequency of coronary artery ectasia in patients undergoing surgery for ascending
      aortic aneurysms.
AB  - We retrospectively studied the coronary arteriograms of 82 consecutive patients
      who underwent planned surgical repair of an ascending aorta aneurysm and an age
      matched control group of 92 consecutive patients who underwent coronary
      angiography during the same time period. The present study examines the incidence
      of coronary artery ectasia in patients with aneurysms of the ascending aorta.

PMID- 15566921
TI  - Usefulness of procainamide challenge for electrophysiologic arrhythmia risk
      stratification.
AB  - Among 58 consecutive patients who underwent electrophysiologic testing for risk
      assessment and who subsequently received a third-generation implantable
      cardioverter-defibrillator, 39 had ventricular tachycardia induced in the
      baseline state and 19 had ventricular tachycardia induced only after
      administration of intravenous procainamide, increasing the yield of
      electrophysiologic risk assessment by 49%. At follow-up, ventricular arrhythmias
      requiring implantable cardioverter-defibrillator termination occurred in 14 of 39
      patients inducible in the baseline state and in 7 of 19 patients inducible only
      with intravenous procainamide. The provocative use of intravenous procainamide
      during electrophysiologic risk assessment increases the detection rate for risk
      of sustained ventricular arrhythmias with no loss of positive predictive value.

PMID- 15566922
TI  - Comparison of rectilinear biphasic waveform energy versus truncated exponential
      biphasic waveform energy for transthoracic cardioversion of atrial fibrillation.
AB  - Success rates of cardioversion with a defibrillator using the truncated
      exponential biphasic waveform (with a maximum energy of 360 J) and a
      defibrillator using the rectilinear biphasic waveform (with a maximum energy of
      200 J) were randomly compared in 145 patients. Success rates at 50, 100, 150, and
      200 J were not significantly different, but 2 patients who did not achieve
      cardioversion after a 200-J maximum energy shock by the rectilinear device
      underwent successful cardioversion with a 360-J shock by the truncated
      exponential device after crossover.

PMID- 15566923
TI  - Findings on magnetic resonance imaging of idiopathic right ventricular outflow
      tachycardia.
AB  - We evaluated 20 patients with idiopathic ventricular tachycardia for structural
      abnormalities using magnetic resonance imaging (MRI) and compared them with 20
      controls. Two experienced observers interpreted the MRIs. There were no
      differences in incidence of qualitative MRI findings in patients compared with
      controls. These findings do not favor an association between anatomic
      abnormalities and arrhythmia in these patients.

PMID- 15566924
TI  - Upper limit of vulnerability determination during implantable cardioverter
      defibrillator placement to minimize ventricular fibrillation inductions.
AB  - The defibrillation threshold (DFT) and upper limit of vulnerability (ULV) were
      determined using step-down protocols in 50 patients who underwent implantable
      cardioverter-defibrillator placement or testing. The sensitivity and specificity
      of each ULV energy level was assessed for detecting an increased DFT, correlation
      of the DFT and ULV, and optimal shock timing for ULV determination. A ULV <10 or
      11 J (failure to induce ventricular fibrillation with 10- to 11-J shocks) was
      100% predictive of an acceptable DFT and may be sufficient to exclude
      unacceptable DFTs in 60% of implantable cardioverter-defibrillator recipients.
      All 4 shocks used to scan the peak of the T wave during ULV testing were
      necessary for accurate ULV determination.

PMID- 15566925
TI  - Noninvasive mapping of left ventricular electromechanical asynchrony by three
      dimensional echocardiography and semi-automatic contour detection.
AB  - A system for analyzing left ventricular (LV) electromechanical asynchrony based
      on transesophageal 3-dimensional echocardiography (3-DE) and semi-automatic
      endocardial contour detection is described. Eighteen consecutive patients
      underwent 3-DE. Using TomTec 4DLV software, a 3-dimensional endocardial surface
      was reconstructed throughout the cardiac cycle. Matlab software generated color
      coded polar maps, displaying regional LV displacement and its timing. At the
      segmental level, Bland-Altmann assessment showed intraobserver variability of LV
      displacement of 0.1 +/- 3.0 mm and timing of -5.6 +/- 160 ms (bias +/- 2 SD) for
      all segments and -1.6 +/- 94 ms for the nonapical segments. The combination of 3
      DE and semi-automatic contour detection is feasible and provides unique
      information for assessing regional LV endocardial displacement and
      electromechanical asynchrony.

PMID- 15566926
TI  - Effects of hormone replacement therapy or raloxifene on ambulatory blood pressure
      and arterial stiffness in treated hypertensive postmenopausal women.
AB  - The administration of oral raloxifene in 30 postmenopausal hypertensive women was
      evaluated to demonstrate its effect on arterial stiffness. Casual and ambulatory
      blood pressure (BP) and pulse-wave velocity (PWV) data were obtained before and
      after patients received raloxifene, estrogen-progestin replacement therapy, or
      placebo in a randomized crossover study. It was shown that the 2 therapies
      decreased BP and carotid-femoral PWV, and the effect of raloxifene on vascular
      compliance was independent of the effects on BP.

PMID- 15566927
TI  - Early detection by the Tei index of carvedilol-induced improved left ventricular
      function in patients with heart failure.
AB  - Twenty-two patients (19 men) with heart failure (16 ischemic, 6 dilated
      cardiomyopathy; mean age of 67 +/- 6 years) in New York Heart Association classes
      I (2 patients), II (18 patients), and III (2 patients) under optimal therapy were
      strictly monitored after carvedilol supplementation. The Tei index decreased
      significantly from 0.87 +/- 0.17 to 0.53 +/- 0.29 (p <0.03). Conversely, the
      ejection fraction and transmitral Doppler flow analysis did not show significant
      improvement, despite a trend toward the amelioration of the ejection fraction,
      the E-/A-wave ratio, and atrial contribution. The Tei index could represent an
      earlier marker to evaluate drug-induced left ventricular function improvement in
      patients with heart failure and could represent a more sensitive tool to monitor
      left ventricular function during drug interventions.

PMID- 15566928
TI  - Relation of dose of carvedilol to reduction in QT dispersion in patients with
      mild to moderate heart failure secondary to ischemic or to idiopathic dilated
      cardiomyopathy.
AB  - Carvedilol has been shown to improve survival and morbidity in patients with
      heart failure. It has been demonstrated that carvedilol use is associated with
      dose-dependent reduction in QT dispersion (QTd) independent of the cause of heart
      failure, suggesting that reduction in QTd may be a mechanism by which carvedilol
      improves outcomes in heart failure.

PMID- 15566929
TI  - Effect of cardiac resynchronization therapy on functional mitral regurgitation in
      heart failure.
AB  - Cardiac resynchronization therapy (CRT) reduces functional mitral regurgitation
      (MR) at rest. This study assessed exercise-induced changes in MR in patients with
      heart failure who were helped by CRT. The determinants of these exercise-induced
      changes in MR were analyzed in asynchronous and resynchronized left ventricles.

PMID- 15566930
TI  - Survey of the use of organic nitrates for the treatment of chronic congestive
      heart failure in the United States.
AB  - A survey of members of the Heart Failure Society of America revealed that despite
      their lack of approval by the United States Food and Drug Administration,
      nitrates are widely used in patients with chronic congestive heart failure (CHF).
      Most members reported using nitrates in patients with ischemic (90%) and
      nonischemic (81%) causes of chronic CHF, especially those with symptomatic CHF
      (43% reported using nitrates in >50% of their patients with ischemic and 25% with
      nonischemic causes). Ninety-six percent reported using nitrates to reduce
      symptoms, 74% for hemodynamic improvement, 65% for better exercise tolerance, and
      only 14% for left ventricular reversed remodeling. Nitrates were always combined
      with hydralazine in 25% of patients and occasionally combined with hydralazine in
      67%.

PMID- 15566931
TI  - Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy.
AB  - Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in
      patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum
      tenascin-C levels were increased in proportion to the severity of left
      ventricular dysfunction in patients with IDC. The associations of serum tenascin
      C levels with serum troponin T and procollagen type III aminoterminal peptide
      levels suggest that increased levels of serum tenascin-C indicate ongoing
      replacement fibrosis after myocardial damage in IDC.

PMID- 15566932
TI  - Preoperative risk stratification for endovascular surgery using pharmacologic
      stress myocardial imaging.
AB  - To stratify perioperative cardiac risk for endovascular surgery, pharmacologic
      stress single-photon emission computed tomography (SPECT) was performed in 206
      patients. Of 8 patients who had cardiac events, 7 occurred in 67 patients with
      positive SPECT results, whereas only 1 occurred in 139 patients with negative
      SPECT results (7 of 67 vs 1 of 139, p <0.002). Furthermore, a scintigraphic
      marker of a summed stress score >/=14 was the most important factor identifying
      patients who subsequently had cardiac events by multivariate analysis.

PMID- 15566933
TI  - Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in
      severe heart failure.
AB  - This study sought to evaluate the utility of sildenafil in assessing pulmonary
      artery reactivity in left-sided cardiac failure and secondary pulmonary
      hypertension (PH). Fourteen consecutive patients with heart failure were studied,
      with oral doses of either sildenafil 25 mg (n = 8) or 50 mg (n = 6) every 8 hours
      for </=3 doses, and invasive serial hemodynamic measurements were performed.
      Thirteen patients (93%) demonstrated >20% decreases in pulmonary artery
      pressures. There was also a 20% reduction of the pulmonary vascular
      resistance/systemic vascular resistance ratio, indicating relative pulmonary
      artery selectivity. Compared with sildenafil 25 mg, sildenafil 50 mg demonstrated
      greater reductions of pulmonary pressures. Oral sildenafil is safe and effective
      for the evaluation of PH reactivity in heart failure.

PMID- 15566934
TI  - Impact of body mass index on in-hospital outcomes following percutaneous coronary
      intervention.

PMID- 15566935
TI  - Clinical and therapeutic implications of troponin elevation in cardiac arrest.

PMID- 15566936
TI  - Which role of echocardiography to predict systemic embolism in dilated
      cardiomyopathy?

PMID- 15566937
TI  - Neurobiology of decreased heart rate variability in older patients with recent
      acute coronary syndrome.

PMID- 15566939
TI  - Molecular cloning of the chicken ST2 gene and a novel variant form of the ST2
      gene product, ST2LV.
AB  - The ST2 gene encodes receptor-like molecules that are very similar to the
      interleukin-1 receptors. Three types of ST2 gene products, ST2, ST2L, and ST2V,
      can be produced by alternative splicing. In the course of cloning the chicken ST2
      and ST2L cDNAs, we identified a novel variant cDNA other than ST2, ST2L, or ST2V,
      and tentatively named it ST2LV. ST2LV was produced by alternative splicing that
      deleted the transmembrane domain of ST2L. The chicken ST2 gene consisted of 13
      exons and had two promoters followed by noncoding exons 1a and 1b, like the ST2
      genes of human, mouse, and rat. The chicken ST2 mRNA was detected by RT-PCR as
      early as embryonic day 5. After that, the chicken ST2 mRNA was expressed in all
      examined organs, including the brain, eye, heart, lung, and liver. The chicken
      ST2LV mRNA was detected from embryonic day 10. The chicken ST2LV cDNA was
      transiently expressed in COS-7 cells. A protein of 69 kDa was detected in the
      culture supernatant, and the size of the protein was reduced to 53 kDa by
      treatment with peptide-N-glycosidase F, which suggested that ST2LV is a new
      soluble secreted and N-glycosylated variant of the ST2 gene product.

PMID- 15566940
TI  - Selective transcription of p53 target genes by zinc finger-p53 DNA binding domain
      chimeras.
AB  - Active p53 stimulates the transcription of a number of key genes, including the
      pro-apoptotic gene bax, as well as p21, a cell cycle regulator. In this study we
      constructed novel chimeric zinc finger-p53 DNA binding domain (DBD) transcription
      factors designed to bind to the promoters of specific p53 regulated genes. In
      order to selectively increase the expression of Bax, we coupled a pre-selected
      three-zinc finger (Zif) peptide targeted to a sequence in the bax promoter to a
      minimal p53 DBD. This chimeric protein could increase reporter gene transcription
      from a minimal bax promoter (up to 10-fold) but not from a minimal p21 promoter
      in p53-deficient Saos-2 cells. However, fusion proteins carrying longer p53 DBDs
      displayed entirely different selectivity and potency. Thus, Zif-p53 DBD chimeras
      containing N- and C-terminal extensions of the minimal DBD could increase
      transcription driven by a minimal p21 promoter up to 800-fold. These chimeras
      preferred the minimal p21 promoter up to 500-fold over the minimal bax promoter.
      Additionally, endogenous p21 message and protein levels were increased in cells
      expressing the p21 selective Zif-p53 DBD chimera and expression of the chimeric
      proteins resulted in partial cell cycle arrest. Cell fractionation experiments
      indicated that the Zifs enhanced nuclear localization of the Zif-p53 DBD chimera.
      These studies suggest that it is possible to create chimeric transcription
      factors able to strongly and selectively activate genes downstream of p53.

PMID- 15566941
TI  - Transcriptional regulation of the IAPP gene in pancreatic beta-cells.
AB  - Islet amyloid polypeptide (IAPP or amylin) is co-secreted with insulin from the
      pancreatic beta-cells. Transcription of the IAPP gene is controlled by a complex
      promoter region, spanning from -2798 to +450 relative to the transcriptional
      start site. In the present study, we have used reporter gene analysis and semi
      quantitative RT-PCR to establish that insulin, glucagon, glucagon-like peptide-1
      (GLP-1) and the GLP-1 derivatives GLP(7-36)Amide and Exendin-4 all stimulate IAPP
      promoter activity, as well as endogenous IAPP mRNA levels in isolated islets of
      Langerhans. In contrast, somatostatin had no effect, and whilst the inflammatory
      cytokines TNF-alpha, IL-1alpha and IL-1beta had no effect on promoter activity,
      they all decreased IAPP mRNA levels in isolated islets. Finally, utilising a
      series of deletion reporter gene constructs of the human IAPP gene promoter, we
      used overexpression studies to establish that HNF-3beta (FoxA2) negatively
      regulates the IAPP promoter, whilst the MODY3 transcription factor HNF-1alpha
      positively regulates promoter activity.

PMID- 15566942
TI  - Induction of gene expression of xenobiotic metabolism enzymes and ABC-transport
      proteins by PAH and a reconstituted PAH mixture in human Caco-2 cells.
AB  - It was shown recently that in epithelial Caco-2 cells the food contaminant
      benzo[a]pyrene (B[a]P) is metabolized and B[a]P-sulfate metabolites were
      transported out of the cells. The aim of this study was to investigate whether
      B[a]P and other polycyclic aromatic hydrocarbons (PAH) such as chrysene,
      phenanthrene, benzo[k]fluoranthene (B[k]F), dibenzo[a,l]pyrene (DB[a,l]P), and
      pyrene alone or in a mixture in a ratio as they occur in tobacco smoke have
      effects on gene expression of intestinal cytochrome P450 enzymes (CYP), Phase II
      enzymes and ATP-binding cassette (ABC)-transport proteins in the human Caco-2
      cells. B[a]P induced its own metabolism. Treatment of the Caco-2 cells with
      B[a]P, chrysene, B[k]F, or DB[a,l]P induced mRNA expression of CYP1A1 and CYP1B1
      specifically as measured by RT-PCR. In contrast, the mRNA expression of the
      microsomal epoxide hydrolase (mEH) was not affected by PAH. The gene expression
      of the Phase II enzymes UDP-glucuronosyltransferase 1A6 (UGT1A6) and UGT1A7 was
      also induced by these PAH but treatment with them had no effect on gene
      expression of sulfotransferases (SULT) at all. Of the ABC-transport proteins,
      MDR1 mRNA expression was induced by treatment with carcinogenic PAH, whereas MRP2
      mRNA expression was not changed. The mixture of PAH also induced CYP1A1, CYP1B1,
      UGT1A6, and UGT1A7 mRNA expression. We conclude that B[a]P, chrysene, B[k]F, and
      DB[a,l]P have specific effects on intestinal CYP1A1, CYP1B1, UGT1A6, and UDP1A7
      mRNA expression but no effects on the expression of SULT.

PMID- 15566943
TI  - Characterization of the promoter of the mouse c-Jun NH2-terminal/stress-activated
      protein kinase alpha gene.
AB  - We report the isolation of the mouse JNK/SAPKalpha gene, the determination of its
      exon/intron organization and the characterization of its promoter region. The
      mouse JNK/SAPKalpha gene spans a region of 36 kbp and contains 13 exons, which
      represent about 8% of the gene sequence. Major JNK/SAPKalpha splice variants (I
      and II) are generated by alternative splicing of exons 7 and 8, respectively,
      whereas minor variants (III and IV) are generated using cryptic sites located
      inside exon 9. The regulatory elements of the JNK/SAPKalpha gene are located in a
      400-bp region placed upstream of the first exon. The gene lacks a TATA element
      and the initiation of transcription is located inside a 1-kbp CG island. Two
      regulatory regions located at -98/-69 and -69/-30 were defined by deletion
      analysis of the promoter.

PMID- 15566944
TI  - Molecular cloning and characterization of a human urate transporter (hURAT1) gene
      promoter.
AB  - We report the novel cloning and preliminary characterization of a human urate
      transporter (hURAT1) gene promoter. The transcription initiation site was mapped
      to a base 337 bp upstream of the ATG start codon by primer extension and 5'-RACE.
      The minimal functional promoter region is within 253 bp when the
      promoter/luciferase constructs were transfected into OK cells. The sex hormone
      testosterone significantly increases promoter activity, suggesting that hormonal
      regulation of hURAT1 is the root cause of observed differences in urate levels
      between males and females.

PMID- 15566945
TI  - Life history of wild Sumatran orangutans (Pongo abelii).
AB  - We present life history data on wild Sumatran orangutans gleaned from a 32-year
      and a 5.5-year study. Estimated age at first reproduction was 15.4 years. At 9.3
      years, the average interbirth interval for this population is the longest ever
      recorded for any great ape population, significantly longer than that of a
      Bornean orangutan population. We find that age-specific mortality of Sumatran
      orangutans does not differ between sexes and is significantly lower than that of
      wild chimpanzees. We conclude that orangutan life history is the slowest among
      extant great apes. In accordance with their slow life history, longevity in the
      wild is estimated to be at least 58 years for males and at least 53 for females.
      We find no evidence for menopause. These data suggest that compared to the
      ancestral state, humans have undergone less of an increase in longevity than
      commonly assumed, and have experienced selection on earlier cessation of
      reproduction.

PMID- 15566946
TI  - Inferring hominoid and early hominid phylogeny using craniodental characters: the
      role of fossil taxa.
AB  - Recent discoveries of new fossil hominid species have been accompanied by several
      phylogenetic hypotheses. All of these hypotheses are based on a consideration of
      hominid craniodental morphology. However, Collard and Wood (2000) suggested that
      cladograms derived from craniodental data are inconsistent with the prevailing
      hypothesis of ape phylogeny based on molecular data. The implication of their
      study is that craniodental characters are unreliable indicators of phylogeny in
      hominoids and fossil hominids but, notably, their analysis did not include
      extinct species. We report here on a cladistic analysis designed to test whether
      the inclusion of fossil taxa affects the ability of morphological characters to
      recover the molecular ape phylogeny. In the process of doing so, the study tests
      both Collard and Wood's (2000) hypothesis of character reliability, and the
      several recently proposed hypotheses of early hominid phylogeny. One hundred and
      ninety-eight craniodental characters were examined, including 109 traits that
      traditionally have been of interest in prior studies of hominoid and early
      hominid phylogeny, and 89 craniometric traits that represent size-corrected
      linear dimensions measured between standard cranial landmarks. The characters
      were partitioned into two data sets. One set contained all of the characters, and
      the other omitted the craniometric characters. Six parsimony analyses were
      performed; each data set was analyzed three times, once using an ingroup that
      consisted only of extant hominoids, a second time using an ingroup of extant
      hominoids and extinct early hominids, and a third time excluding Kenyanthropus
      platyops. Results suggest that the inclusion of fossil taxa can play a
      significant role in phylogenetic analysis. Analyses that examined only extant
      taxa produced most parsimonious cladograms that were inconsistent with the ape
      molecular tree. In contrast, analyses that included fossil hominids were
      consistent with that tree. This consistency refutes the basis for the hypothesis
      that craniodental characters are unreliable for reconstructing phylogenetic
      relationships. Regarding early hominids, the relationships of Sahelanthropus
      tchadensis and Ardipithecus ramidus were relatively unstable. However, there is
      tentative support for the hypotheses that S. tchadensis is the sister taxon of
      all other hominids. There is support for the hypothesis that A. anamensis is the
      sister taxon of all hominids except S. tchadensis and Ar. ramidus. There is no
      compelling support for the hypothesis that Kenyanthropus platyops shares
      especially close affinities with Homo rudolfensis. Rather, K. platyops is nested
      within the Homo + Paranthropus + Australopithecus africanus clade. If K. platyops
      is a valid species, these relationships suggest that Homo and Paranthropus are
      likely to have diverged from other hominids much earlier than previously
      supposed. There is no support for the hypothesis that A. garhi is either the
      sister taxon or direct ancestor of the genus Homo. Phylogenetic relationships
      indicate that Australopithecus is paraphyletic. Thus, A. anamensis and A. garhi
      should be allocated to new genera.

PMID- 15566947
TI  - Comparison of inverse-dynamics musculo-skeletal models of AL 288-1
      Australopithecus afarensis and KNM-WT 15000 Homo ergaster to modern humans, with
      implications for the evolution of bipedalism.
AB  - Size and proportions of the postcranial skeleton differ markedly between
      Australopithecus afarensis and Homo ergaster, and between the latter and modern
      Homo sapiens. This study uses computer simulations of gait in models derived from
      the best-known skeletons of these species (AL 288-1, Australopithecus afarensis,
      3.18 million year ago) and KNM-WT 15000 (Homo ergaster, 1.5-1.8 million year ago)
      compared to models of adult human males and females, to estimate the required
      muscle power during bipedal walking, and to compare this with those in modern
      humans. Skeletal measurements were carried out on a cast of KNM-WT 15000, but for
      AL 288-1 were taken from the literature. Muscle attachments were applied to the
      models based on their position relative to the bone in modern humans. Joint
      motions and moments from experiments on human walking were input into the models
      to calculate muscle stress and power. The models were tested in erect walking and
      'bent-hip bent-knee' gait. Calculated muscle forces were verified against EMG
      activity phases from experimental data, with reference to reasonable
      activation/force delays. Calculated muscle powers are reasonably comparable to
      experimentally derived metabolic values from the literature, given likely values
      for muscle efficiency. The results show that: 1) if evaluated by the power
      expenditure per unit of mass (W/kg) in walking, AL 288-1 and KNM-WT 15000 would
      need similar power to modern humans; however, 2) with distance-specific
      parameters as the criteria, AL 288-1 would require to expend relatively more
      muscle power (W/kg.m(-1)) in comparison to modern humans. The results imply that
      in the evolution of bipedalism, body proportions, for example those of KNM-WT
      15000, may have evolved to obtain an effective application of muscle power to
      bipedal walking over a long distance, or at high speed.

PMID- 15566948
TI  - Hepatitis intensified oxidative stress, MIP-1beta and RANTES plasma levels in
      uraemic patients.
AB  - HBV and HCV infections are associated with the increased production of reactive
      oxygen species (ROS) within the liver that are responsible for the oxidation of
      intracellular molecules and activation transcription factors. The aim of the
      present study was to establish whether the presence of hepatitis could be
      implicated in the elevation of oxidative stress (SOX) and plasma proinflammatory
      and chemoattractant cytokine levels in uraemic patients. The markers of SOX
      autoantibodies to oxidized LDL (OxLDL-Ab); total peroxides; and the major
      antioxidant enzyme Cu/Zn superoxide dismutase (Cu/Zn SOD); as well as tumor
      necrosis factor-alpha (TNF-alpha); regulated upon activation, normal T cell
      expressed and secreted (RANTES); and macrophage inflammatory protein-1alpha (MIP
      1alpha) and beta (MIP-1beta) levels were measured in the plasma of uraemic
      patients with hepatitis in comparison to subjects without hepatitis and to
      healthy volunteers. The values of total peroxide, Cu/Zn SOD, TNF-alpha, and MIP
      1beta, were significantly elevated in uraemic patients when compared to the
      controls, whereas RANTES were decreased. MIP-1alpha and OxLDL-Ab were similar in
      the two groups. Cu/Zn SOD, MIP-1beta and RANTES concentrations were significantly
      higher in the hepatitis-positive relative to the hepatitis-negative group. Both
      MIP-1beta and RANTES were directly associated with Cu/Zn SOD levels and the
      presence of hepatitis. Multiple stepwise regression analysis has shown that the
      duration of dialysis, followed by the presence of hepatitis, independently and
      significantly predicted increased Cu/Zn SOD levels, whereas elevated Cu/Zn SOD as
      an independent variable was significantly associated with both increased both MIP
      1beta and RANTES in uraemic patients. These results suggest that the presence of
      viral hepatitis status and liver injury are novel determinants of increased
      oxidative stress, as well as of increased MIP-1beta and RANTES levels in uraemic
      patients.

PMID- 15566949
TI  - Modulation of cytokine profiles by malaria pigment--hemozoin: role of IL-10 in
      suppression of proliferative responses of mitogen stimulated human PBMC.
AB  - The malaria parasite pigment hemozoin (Hz) is internalized by circulating and
      resident phagocytes and modulates their functions. We report here that Hz from
      Plasmodium falciparum inhibits proliferative responses of PHA stimulated human
      peripheral blood mononuclear cells (PBMC) in a dose dependent manner. Hz
      phagocytosed monocyte/macrophages (MO/MQ) secreted high levels of IL-10, IL-1beta
      and TNF-alpha, but inhibition of proliferation was mediated by IL-10 alone which
      was reversed by neutralization of the cytokine. Drastic decrease in the levels of
      IL-2, IL-12 and IFN-gamma were observed in supernatants from PBMC stimulated in
      the presence of Hz loaded MO/MQ cells. Exogenous addition of these cytokines did
      not abrogate immunosuppression indicating the inability of these cytokines to
      enhance proliferation in the presence of IL-10. We provide additional data that
      the IL-10 levels correlated positively with the load of Hz in the MO/MQ. Kinetics
      of IL-10 secretion analyzed up to day 6 in MO/MQ cultures fed with Hz revealed
      that high levels of IL-10 were secreted during the first 48 h after ingestion and
      decreased drastically at later time points.

PMID- 15566950
TI  - Modulation of endotoxin stimulated interleukin-6 production in monocytes and
      Kupffer cells by S-adenosylmethionine (SAMe).
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine having primarily anti
      apoptotic and anti-inflammatory effects. Recent reports have documented that IL-6
      plays a key role in liver regeneration. Intracellular deficiency of S
      adenosylmethionine (SAMe) is a hallmark of toxin-induced liver injury. Although
      the administration of exogenous SAMe attenuates liver injury, its mechanisms of
      action are not fully understood. Here we investigated the effects of exogenous
      SAMe on IL-6 production in monocytes and Kupffer cells. RAW 264.7 cells, a murine
      monocyte cell line, and isolated rat Kupffer cells were stimulated with
      lipopolysaccharide (LPS) in the absence or presence of exogenous SAMe. IL-6
      production was assayed by ELISA and intracellular SAMe concentrations were
      measured by HPLC. We have found that exogenous SAMe administration enhanced both
      IL-6 protein production and gene expression in LPS-stimulated monocytes and
      Kupffer cells. Cycloleucine (CL), an inhibitor for extrahepatic methionine
      adenosyltransferases (MAT), inhibited LPS-stimulated IL-6 production. The
      enhancement of LPS-stimulated IL-6 production by SAMe was inhibited by ZM241385,
      a specific antagonist of adenosine (A2) receptor. Our results demonstrate that
      SAMe administration may exert its anti-inflammatory and hepatoprotective effects,
      at least in part, by enhancing LPS-stimulated IL-6 production.

PMID- 15566951
TI  - Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation
      and airway remodeling.
AB  - Asthma is a chronic inflammatory disease characterized by reversible bronchial
      constriction, pulmonary inflammation and airway remodeling. Current standard
      therapies for asthma provide symptomatic control but fail to target the
      underlying disease pathology. Furthermore, no therapeutic agent is effective in
      preventing airway remodeling. Interleukin 13 (IL-13) is a pleiotropic cytokine
      produced mainly by T cells. A substantial amount of evidence suggests that IL-13
      plays a critical role in the pathogenesis of asthma. Therefore, a neutralizing
      anti-IL-13 monoclonal antibody could provide therapeutic benefits to asthmatic
      patients. To test the concept we have generated a neutralizing rat anti-mouse IL
      13 monoclonal antibody, and evaluated its effects in a chronic mouse model of
      asthma. Chronic asthma-like response was induced in ovalbumin (OVA) sensitized
      mice by repeated intranasal OVA challenges. After weeks of challenge, mice
      developed airway hyperresponsiveness (AHR) to methacholine stimulation, severe
      airway inflammation, hyper mucus production, and subepithelial fibrosis. When
      given at the time of each intranasal OVA challenge, anti-IL-13 antibody
      significantly suppressed AHR, eosinophil infiltration, proinflammatory
      cytokine/chemokine production, serum IgE, and most interestingly, airway
      remodeling. Taken together, these results strongly suggest that a neutralizing
      anti-human IL-13 monoclonal antibody could be an effective therapeutic agent for
      asthma.

PMID- 15566952
TI  - Cytokine gene polymorphisms in endemic pemphigus foliaceus: a possible role for
      IL6 variants.
AB  - Endemic pemphigus foliaceus (EPF) is a complex autoimmune disease characterized
      by the presence of antibodies against desmoglein 1, which lead to the loss of
      adhesion among keratinocytes (acantholysis). Variants of HLA class II genes have
      been the only genetic factors found to modulate susceptibility to EPF. This study
      aims at investigating the influence of cytokine genetic variants in the
      pathogenesis of EPF, since they may affect the expression levels of these
      immunomodulatory molecules. The sample included 168 patients and 189 controls and
      was comprised of mostly Caucasoids and Mulattos. The approach consisted of a case
      control association study and the alleles were identified by mismatched PCR-RFLP.
      No associations were found with variants of IL1A, IL1B, IL1RN, IL4R and IL10.
      There was a weak negative association with the haplotype -1082G -592C (OR=0.49)
      of the IL10 gene in Mulattos. In regard to polymorphism -590 of the IL4 gene, a
      positive association with the T/T genotype (OR=2.71) and a negative association
      with the C variant (OR=0.37) were found. Associations with IL6 -174 variants
      suggest that the C/C genotype has a protective effect (OR=0.13) while carriers of
      the G allele are more susceptible (OR=7.66) to EPF.

PMID- 15566953
TI  - Stabilization of macromolecular chromatin complexes in mitotic chromosomes by
      light irradiation in the presence of ethidium bromide.
AB  - A method was developed for stabilizing mitotic chromosomes. Light irradiation of
      permeabilized cells in a low concentration of ethidium bromide made chromatin
      resistant to high salt concentrations and decondensing buffer. This resistance
      was abolished by proteinase treatment, but not by DNase or RNase treatment. In
      photostabilized and extracted chromosomes, chromatin appeared as thick fibers
      with discrete high electron density regions. These stabilized structures might
      correspond to the higher-level structures (chromonemata) observed in native
      chromatin. Moreover, the electron density was higher in the centromeric regions
      than the chromosome arm material. Thus, the method allows chromatin substructures
      (chromonemata and centromeric heterochromatin) to be stabilized inside mitotic
      chromosomes.

PMID- 15566954
TI  - Subnucleolar distribution and organization of Vicia faba L. rDNA in situ.
AB  - The distribution and organization of nucleolar DNA in Vicia faba L. was analyzed
      by specific cytochemical staining using NAMA-Ur. The results showed that
      nucleolar DNA was distributed in the FCs and at the FC/DFC junctions. Statistical
      analysis showed that the rRNA genes occupied about one-third of the total dense
      fibrillar component region. The rDNA was condensed in some regions and
      uncondensed in others. Nucleolus-associated chromatin extended from outside the
      nucleolus to the periphery of the FCs via nucleolar channels, suggesting a
      possible origin for nucleolar DNA.

PMID- 15566955
TI  - FGF-2 and S100beta immunoreactivities increase in reactive astrocytes, but not in
      microglia, in ascending dopamine pathways following a striatal 6-OHDA-induced
      partial lesion of the nigrostriatal system.
AB  - Partial lesions were induced in rat midbrain dopamine ascending pathways by
      intrastriatal injection of 6-hydroxydopamine (6-OHDA), and after two weeks
      changes were observed in the immunoreactivities of S100beta, a calcium-binding
      protein, and basic fibroblast growth factor (FGF-2), which is neurotrophic.
      Semiquantitative microdensitometric image analysis revealed increased intensities
      of FGF-2 and S100beta immunostaining in putative glial profiles of the
      ipsilateral neostriatum, pars compacta (SNc) and reticulata (SNr) of the
      substantia nigra and ventral tegmental area (VTA). Double immunofluorescence and
      immunoperoxidase procedures, using antibodies against glial fibrillary acidic
      protein and OX-42, showed that these increased immunoreactivities were restricted
      to reactive astrocytes; they were not observed in reactive microglia. These
      results indicate that reactive astrocytes may exert paracrine trophic actions
      through S100beta and FGF-2 in the midbrain dopamine ascending pathways after
      striatal 6-OHDA treatment. Interactions between S100beta and FGF-2 may be
      relevant to neuronal maintenance and repair following dopamine injury.

PMID- 15566956
TI  - Connective tissue growth factor regulates the key events in tubular epithelial to
      myofibroblast transition in vitro.
AB  - Connective tissue growth factor (CTGF) has been reported to play an important
      role in mediating the profibrotic effects of transforming growth factor-beta (TGF
      beta) in various renal diseases. To elucidate the role of CTGF in renal tubular
      epithelial-myofibroblast transdifferentiation, we examined the expression of
      alpha-smooth muscle actin (alpha-SMA), vimentin, tenascin-C, and collagen IV
      expression upon the stimulation of CTGF in cultured human proximal tubular
      epithelial cell line (HKC), and further investigated the effects of endogenous
      CTGF blockade on the transdifferentiation process induced by TGF-beta. It is
      revealed that upon the stimulation of recombinant human CTGF (rhCTGF, 2.5 or 5.0
      microg/L), the expression of alpha-SMA and tenascin-C mRNA increased
      significantly (p<0.01), while collagen IV gene expression decreased significantly
      (p<0.01), all in a dose-dependent manner. The percentage of alpha-SMA-positive
      cells was significantly larger in the rhCTGF-stimulated groups than that in
      negative control (38.9%, 65.5% vs. 2.4%, respectively, p<0.01) as confirmed by
      flow cytometry. Both cytoplasmic and secretory tenascin-C expression was
      upregulated by the stimulation of rhCTGF (p<0.01). Under this condition, collagen
      IV secreted into the culture media was lowered markedly (p<0.01). On RT-PCR
      analysis, TGF-beta1 upregulated CTGF gene expression, preceding that of alpha
      SMA. The alpha-SMA mRNA expression induced by TGF-beta1 was significantly
      inhibited by CTGF antisense oligodeoxynucleotide (ODN) transfection (p<0.01).
      With prolonged incubation time, CTGF antisense ODN also inhibited intracellular
      alpha-SMA protein synthesis, as demonstrated by indirect immuno-fluorescence. So
      it is concluded that CTGF could promote the transdifferentiation of human renal
      tubular epithelial cells towards myofibroblasts in vitro, both directly and as a
      downstream mediator of TGF-beta, and CTGF blockade would be a possible
      therapeutic target against tubulointerstitial fibrosis.

PMID- 15566957
TI  - Hyperphosphorylation of extracellular regulated kinase 2 (ERK2) and inhibition of
      JNK2 phosphorylation are associated with increased S-phase during transformation
      of Syrian hamster embryo cells by Malachite Green.
AB  - Malachite Green (MG), consisting of green crystals with a metallic lustre, is
      highly soluble in water, cytotoxic to various mammalian cells and also acts as a
      liver tumour promoter. In view of its industrial importance and possible exposure
      to human beings, MG poses a potential environmental health hazard. We have
      earlier reported the malignant transformation of Syrian hamster embryo (SHE)
      cells in primary culture by MG. In this study, we have studied the mitogen
      activated protein (MAP) kinase signal transduction pathway in preneoplastic cells
      induced by MG. Western blots of MG induced preneoplastic cells showed no
      phosphorylation of ERK1, an increased phosphoactive ERK2 associated with a
      decreased expression of phosphoactive JNK2. However, total forms of ERKs, JNKs
      and p38 Kinases showed similar levels of expression in control and preneoplastic
      SHE cells. Indirect immunofluorescence studies have shown a distinct nuclear
      localisation of phosphoactive ERKs in MG induced preneoplastic cells. Flow
      cytometric analysis showed an increase of S-phase cells in preneoplastic cells
      compared to control SHE cells. The present study indicates that
      hyperphosphorylation of ERK2, decreased JNK2 phosphorylation and an increase in S
      phase cells seems to be the early changes associated with the MG induced
      malignant transformation of SHE cells in primary culture.

PMID- 15566958
TI  - Muscular myosin isoforms of Taenia solium (Cestoda).
AB  - Type II myosin, the primary component of the thick filament of muscle fibers, is
      organized as a dimeric high molecular weight protein, and is composed of a pair
      of heavy chains (MHC) and two pairs of light chains. Myosin II transforms ATP
      energy into mechanical force. All type II myosins are conserved proteins but they
      have two variable regions that are located in different places of the molecule.
      Myosin molecules are encoded by a multigene family and many isoforms are
      generated. The expression of myosins depends on the developmental stage and on
      the type and degree of contractile activity and tissue, therefore several myosin
      isoforms are found in the same organism. Here we describe the use of different
      techniques that allowed demonstrating the presence of isoforms of the heavy chain
      type II myosin of Taenia solium cysticerci (larvae) and tapeworms (adults), a
      cestode parasite of importance in public health in many developing countries.
      Myosin was purified and used in comparative proteolytic fragmentation, ATPase
      activity, detection of antigenic differences and electrophoretic separation. The
      results obtained showed biochemical and immunochemical differences among
      cysticerci and tapeworms, and demonstrate the presence of myosin isoforms in T.
      solium that are probably associated to physiological requirements of each
      developmental stage.

PMID- 15566959
TI  - Dual apoptotic effect of Xrel3 c-Rel/NF-kappaB homolog in human cervical cancer
      cells.
AB  - Cervical cancer is one of the most common cancers affecting a woman's
      reproductive organs. Despite its frequency and recurrence, the death rate has
      been declining over the past 40 years, due to early detection and treatment. In a
      previous report [Shehata Marlene, Shehata Marian, Shehata Fady, Pater Alan.
      Apoptosis effects of Xrel3 c-Rel/Nuclear factor-kappa B homolog in human cervical
      cancer cells. Cell Biology International, in press], we studied the role of the
      NF-kappaB gene family in HeLa human cervical cancer cells, using the Xrel3 c-Rel
      homologue of Xenopus laevis. These results showed that the expression of Xrel3/c
      Rel slowed cell growth, consistent with an upregulated expression of the cell
      cycle inhibitor p21 and the activated poly(ADP-ribose) polymerase (PARP)
      apoptosis effector. However, in this report, we examined more apoptotic and anti
      apoptotic factors acting upstream and downstream in apoptosis pathways after
      cisplatin treatment of HeLa cervical cancer cells. After 1 microM cisplatin
      treatment, Xrel3 had an anti-apoptotic effect, based on significantly lower
      levels of apoptotic proteins, including caspase-8, caspase-3 and p21. Anti
      apoptotic BAG-1 isoforms were upregulated. After 5 microM cisplatin treatment,
      expression of HeLa Xrel3 had an apoptotic effect, based on significantly
      increased expression of the cell cycle inhibitor p21 and apoptotic proteins,
      including cleaved PARP, caspase-8, and caspase-3. However, anti-apoptotic Bcl-2
      and Bcl-X(L) were elevated and the cell cycle regulator cyclin D1 was slightly
      upregulated with both 1 and 5 microM cisplatin treatment. The HPV E6 oncoprotein
      showed no significant changes. These results support previous conclusions on the
      potential anti-apoptotic effects of c-Rel/NF-kappaB in mild stress environments,
      as opposed to the apoptotic effects associated with high stress conditions [Lake
      BB, Ford R, Kao KR. Xrel3 is required for head development in Xenopus laevis.
      Development 2001; 128(2), 263-73.]. Thus, c-Rel/NF-kappaB may potentially be of
      clinical significance in chemotherapy.

PMID- 15566960
TI  - Metallothionein protects bone marrow stromal cells against hydrogen peroxide
      induced inhibition of osteoblastic differentiation.
AB  - Metallothionein (MT), a cysteine-rich, metal-binding protein, is involved in
      homeostatic regulation of essential metals and protection of cells against
      oxidative injury. It has been shown that oxidative stress is associated with
      pathogenesis of osteoporosis and is capable of inhibiting osteoblastic
      differentiation of bone cells by nuclear factor-kappaB (NF-kappaB). In this
      study, the effect of MT on oxidative stress-induced inhibition of osteoblast
      differentiation was examined. 50-200 microM hydrogen peroxide-induced oxidative
      stress suppressed the osteoblastic differentiation process of primary mouse bone
      marrow stromal cells (BMSCs), manifested by a reduction in the differentiation
      marker alkaline phosphatase (ALP). The presence of exogenous MT (20-500 microM)
      or induction of endogenous MT by ZnCl2 (50-200 microM) could protect BMSCs
      against H2O2-induced inhibition of osteoblastic differentiation, manifested by a
      resumption of H2O2-inhibited ALP activity and ALP positive cells. Furthermore,
      adding exogenous MT or inducing endogenous MT expression impaired H2O2-stimulated
      NF-kappaB signaling. These data indicate the ability of MT to protect BMSCs
      against oxidative stress-induced inhibition of osteoblastic differentiation.

PMID- 15566961
TI  - Review and proposed action of alpha-fetoprotein growth inhibitory peptides as
      estrogen and cytoskeleton-associated factors.
AB  - The (H) human growth-promoting factor, alpha-fetoprotein (AFP), has been reported
      to possess a growth inhibitory motif as an occult epitope in the compactly folded
      circulating form of the protein. Intermediate unfolded forms of the human HAFP
      molecule induced by stress, shock, and high ligand concentrations have revealed
      the presence of an encrypted growth-suppressive segment on the third domain of
      HAFP. A purified linear synthetic 34-mer segment termed the "growth inhibitory
      peptide" (GIP) exhibits various oligomeric forms with complex aggregation
      behaviors, in which dominant trimeric forms were found to be suppressive in
      assays of estrogen-induced growth. While several amino acid analogs of the
      cysteines of the GIP retained inhibitory activity, heavy metal binding and pre
      incubation of the peptides with a variety of cations and hormone ligands were
      found to influence the outcomes of growth bioassays. Smaller segments of the
      original 34-mer were each found to display growth activities of their own, with
      the middle segment (P149b) also showing hydrophobic dye-binding properties.
      Studies of amino acid sequence identity further revealed that the GIP sequences
      displayed identity/similarity matches to both cytoplasmic and nucleus
      cytoskeleton-associated proteins, and experimental evidence served to support
      these findings. That is, the peptide was capable of modulating tubulin
      polymerization, cell shape, and cell-surface aggregation phenomena reminiscent of
      a microtubule-associated protein. Immunofluorescence studies further pinpointed
      the localization of the GIP to cytoplasmic regions of high cytoskeletal density
      in the cell. Because of the involvement of the GIP in experimental models of the
      estrogen receptor/cytoskeleton, a mechanism of action is forwarded in which the
      linear GIP is proposed to be a G-coupled receptor binding ligand that is
      translocated across the plasma membrane via receptor-mediated endocytosis. Thus,
      it was predicted that the linear GIP and possibly its peptidic segments serve as
      decoy ligands to cell-surface receptors in order to gain access to the
      cytoplasmic compartment of the cell.

PMID- 15566962
TI  - Phosphorylation of actin-binding protein (ABP-280; filamin) by tyrosine kinase
      p56lck modulates actin filament cross-linking.
AB  - Actin-binding protein (ABP-280; filamin) is a phosphoprotein present in the
      periphery of the cytoplasm where it can cross-link actin filaments, associate
      with lipid membranes, and bind to membrane surface receptors. Given its function
      and localization in the cell, we decided to investigate the possibility of
      whether it serves as substrate for p56lck, a lymphocyte-specific member of the
      src family of protein tyrosine kinases associated with cell surface
      glycoproteins. The interaction of p56lck with membrane glycoproteins is important
      for cell development and functional activation. Here, we show that purified
      p56lck interacts and catalyzes in vitro kinase reactions. Tyrosine
      phosphorylation by p56lck is restricted to a single peptide of labeled ABP-280
      shown by protease digest. The addition of phorbol ester to cells results in the
      inhibition of phosphorylation of ABP-280 by p56lck. These results show a decrease
      in phosphorylation suggesting conformationally induced regulation. Dynamic light
      scattering confirmed increased actin filament cross-linking due to
      phosphorylation of ABP-280 by p56lck.

PMID- 15566963
TI  - Synapsin IIb interacts with the C-terminal SH2 and SH3 domains of PLCgamma1 and
      inhibits its enzymatic activity.
AB  - To elucidate the function of PLCgamma1, we have investigated the proteins that
      bind to its SH (Src homology) domain. Immunoscreening was performed with purified
      antisera specific for SH223 (two SH2 and one SH3)-binding proteins. Several
      immunoreactive clones were identified as putative binding proteins and one of
      them was identified as synapsin IIb. We demonstrate a stable association between
      PLCgamma1 and synapsin IIb, which binds the carboxyl terminal SH2 and SH3 domains
      of the enzyme and inhibits it.

PMID- 15566964
TI  - The influence of 2-chlorodeoxyadenosine (2-CdA) on the adenine energy charge and
      glutathione content of human erythrocytes.
AB  - We have examined the effect of exposure of human erythrocytes to the new
      chemotherapy drug 2-chlorodeoxyadenosine (2-CdA, cladribine), focusing on the
      glutathione (GSH and GSSG) content and the adenine energy charge (AEC).
      Incubation of erythrocytes with 0.1-5 microg/ml 2-CdA induced no significant
      change in the reduced or total glutathione level or in the AMP and ATP
      concentrations. The ADP concentration increased slightly and the AEC value is in
      the range typical of healthy organisms. Incubation of erythrocytes with 2-CdA
      also caused cell shape changes, converting most of the cells to echinocytes.

PMID- 15566965
TI  - The application of image cytometry to viability assessment in dual fluorescence
      stained fish spermatozoa.
AB  - The viability of spermatozoa has been assessed using SYBR 14 staining for DNA of
      living cells and propidium iodide staining for DNA of degenerate cells. This dual
      staining was performed on four fish species (Siberian sturgeon, Acipenser baerii;
      common carp, Cyprinus carpio; tench, Tinca tinca and wels, Silurus glanis) and
      the proportions of live and dead spermatozoa were assessed by epifluorescence
      microscopy and image cytometry. Ten phase contrast and epifluorescent images were
      recorded per sample, corresponding images were overlaid, and the blended images
      were evaluated for live and dead spermatozoa, represented by green and red
      fluorescence signals. Live/dead proportions were assessed, after dual
      thresholding, by imaging software that counted absolute numbers of objects and
      computed their frequencies. All sperm heads were found to be labelled, emitting
      either green or red light. Mean numbers of spermatozoa per image were in the
      ranges 32-113, 61-105, 48-104 and 29-91 for Siberian sturgeon, common carp, tench
      and wels, respectively. The corresponding proportions of live spermatozoa were in
      the ranges 83.56-94.59%, 93.92-97.02%, 76.14-97.76% and 79.45-83.76%. Standard
      deviations did not exceed 5% of the means. The image cytometric system using dual
      staining with SYBR 14 and propidium iodide was clearly suitable for assessing the
      viability of freshwater fish spermatozoa.

PMID- 15566966
TI  - Trouble with the analysis of nitrite, nitrate, S-nitrosothiols and 3
      nitrotyrosine: freezing-induced artifacts?

PMID- 15566968
TI  - In situ detection and visualization of S-nitrosylated proteins following chemical
      derivatization: identification of Ran GTPase as a target for S-nitrosylation.
AB  - The formation of S-nitrosylated proteins is a nitric oxide-dependent post
      translational modification important in signal transduction, yet the in situ
      detection of S-nitrosylated proteins remains problematic. In this study, we
      adapted a recently developed biotin derivatization approach to visualize S
      nitrosylated proteins in intact cells. This strategy circumvents the use of
      antibodies directed against S-nitrosocysteine, which may have problematic
      specificity, due to epitope instability. Endogenous protein S-nitrosylation could
      be observed in intact cells and in mouse lung sections using fluorophore
      conjugated streptavidin and confocal microscopy, and was enhanced by S
      nitrosothiols and reduced following treatment with the nitric oxide synthase
      inhibitor, L-N-monomethyl arginine. Intriguingly, protein S-nitrosylation was
      detected mainly in the nuclear compartment of cells under baseline conditions and
      was enhanced when nuclear export was blocked with leptomycin B. We also
      determined that the small GTPase Ran, a key regulator of nucleocytoplasmic
      transport, is a target for S-nitrosylation. These findings demonstrate that
      biotin derivatization is a useful approach to detect S-nitrosylated proteins in
      situ in cellular compartments or tissues, and will be useful in the assessment of
      altered S-nitrosylation in pathological conditions.

PMID- 15566969
TI  - Stimulation of inducible nitric oxide synthase by monosodium urate crystals in
      macrophages and expression of iNOS in gouty arthritis.
AB  - From the studies on the involvement of iNOS in arthritis, it is clear that
      attention has focused primarily on rheumatoid arthritis (RA) and osteoarthritis
      (OA). To date, little is known about the role of iNOS in the pathophysiology of
      gouty arthritis (GA). Here, we investigated the significance of iNOS expression
      in cell culture system as well as in GA patients. Gouty crystals monosodium urate
      (MSU) appeared to up-regulate inducible nitric oxide synthase (iNOS) mRNA and
      protein expression in a concentration- and time-dependent manner in RAW264.7
      macrophages. This increase of iNOS expression is attributable to the activation
      of multiple signaling pathways. Evidence for this was initially established by
      inhibitor treatment of cells in the presence of MSU. While the JAK inhibitor
      AG490, the PI3K inhibitor LY294002, and the NFkappaB inhibitor PDTC abrogated
      almost completely the expression of iNOS induced by MSU, the ERK1/2 inhibitor
      PD98059 was only partially effective. Furthermore, the effect of MSU on the
      activation of PI3K/Akt, JAK/STAT, ERK1/2, and NFkappaB signaling molecules was
      carefully examined. Moreover, it was shown that GAS and NFkappaB motifs are
      required for iNOS expression mediated by MSU. In addition, synovial tissues
      obtained from GA patients displayed enhanced expression of iNOS when compared
      with normal synovium. Taken together, these findings provide the first evidence
      for the potential importance of iNOS in the pathogenesis of GA as well as RA and
      OA, and in turn raise the possibility that iNOS may be an ideal target for
      preventive therapy in human arthritis.

PMID- 15566970
TI  - Human gingival mucosal keratinocytes exhibiting anchorage-independent growth
      express increased inducible nitric oxide synthase: regulation by MAP kinases.
AB  - Inducible nitric oxide synthase (iNOS) has been implicated in cancer formation
      because of its vast presence cancer tissues. Studies to support such a role
      during transformation of human cells are very limited. We have developed a cell
      culture system, which renders a more transformed epithelial phenotype. The model
      cells generated from immortalized human gingival mucosal (GM) keratinocytes are
      consisted of less transformed epithelial-like (EPI) cells and more transformed
      fibroblast-like (FIB) cells. The latter exhibit anchorage independent growth
      (AIG). Our data showed that iNOS at mRNA and protein levels was up-regulated in
      more transformed FIB cells in comparison with less transformed EPI cells. FIB
      cells at low passages (p<22) were unstable being able to morphologically and
      functionally revert back to EPI phenotype, while no reversion was observed in FIB
      cells at high passages (p>43). The morphological reversion of FIB cells was
      associated with the reversal of vimentin expression as well as AIG. More
      importantly, these revertants showed reduced levels of iNOS mRNA as well as MAP
      kinase ERK and phospho-ERK protein expression, while FIB cells without reversion
      maintained the expression. Furthermore, the MEK1/2 inhibitor U0126 could reduce
      detectable iNOS mRNA levels suggesting that MAP kinases were upstream regulators
      of iNOS transcription. U0126 caused both morphological and functional reversion
      of FIB cells indicating involvement of MAP kinases in these functions. Taken
      together, we provide evidence for an up-regulation of iNOS in cultured human
      keratinocytes which exhibit AIG. This up-regulation may reflect progressive
      transformation which still requires further changes to reach tumorigenic
      conversion.

PMID- 15566971
TI  - Nitric oxide formation in the oropharyngeal tract: possible influence of
      cigarette smoking.
AB  - Cigarette smoking reduces the level of nitric oxide (NO) in exhaled air by an
      unknown mechanism. The view that part of the effect of cigarette smoking on NO
      production should occur in the oropharyngeal tract is supported by several
      studies. We have therefore compared smokers and non-smokers regarding non
      enzymatic formation of NO from nitrite in the oral cavity since this is a primary
      candidate target for cigarette smoke. We have also looked at NO synthase
      dependent NO formation in the mucosa of the oropharyngeal tract as an alternative
      target for the inhibitory effect induced by cigarette smoke. Smokers exhaled 67%
      lower levels of NO than controls (p<0.01, n=15 each group). We could not detect
      any significant difference in salivary nitrite, nitrate or ascorbate between
      smokers and non-smokers. Mouthwash with the antibacterial agent chlorhexidine
      reduced salivary nitrite (-65%) and exhaled NO levels (-10%) similarly in the two
      groups. Immunohistochemical techniques revealed dense expression of inducible
      (but not endothelial or neuronal) NO synthase in the squamous epithelium of non
      inflamed tonsillar and gingival tissue biopsies. In the same biopsies,
      significant Ca2+ -independent citrulline-forming activity was detected. We found
      no difference between smoking and non-smoking subjects regarding NO-synthase
      expression and in vitro activity. In another group of non-smoking subjects
      (n=10), spraying the oropharyngeal tract with the NO-synthase inhibitor NG
      monomethyl-L-arginine (250 mg) significantly reduced exhaled NO levels for at
      least 30 min (-18%, p<0.01). Our data suggest that cigarette smoking does not
      affect non-enzymatic NO formation from nitrite in saliva. However, NO is also
      formed by inducible NO synthase in the squamous epithelium of the normal
      oropharyngeal tract. We suggest that cigarette smoking may down-regulate
      enzymatic NO formation in the oropharyngeal compartment as well as in the
      bronchial compartment.

PMID- 15566972
TI  - Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-)
      species.
AB  - The conversion of NO into its congeners, nitrosonium (NO+) and nitroxyl (HNO/NO-)
      species, has important consequences in NO metabolism. Dinitrosyl iron complex
      (DNIC) combined with thiol ligands was shown to catalyze the conversion of NO
      into NO+, resulting in the synthesis of S-nitrosothiols (RSNO) both in vitro and
      in vivo. The formation mechanism of DNIC was proposed to involve the intermediate
      release of nitroxyl. Since the detection of hydroxylamine (as the product of a
      rapid reaction of HNO/NO- with thiols) is taken as the evidence for nitroxyl
      generation, we examined the formation of hydroxylamine, RSNO, and nitrite (the
      product of a rapid reaction of NO+ with water) in neutral solutions containing
      iron ions and thiols exposed to NO under anaerobic conditions. Hydroxylamine was
      detected in NO treated solutions of iron ions in the presence of cysteine, but
      not glutathione (GSH). The addition of urate, a major "free" iron-binding agent
      in humans, to solutions of GSH and iron ions, and the subsequent treatment of
      these solutions with NO increased the synthesis of GSNO and resulted in the
      formation of hydroxylamine. This caused a loss of urate and yielded a novel
      nitrosative/nitration product. GSH attenuated the urate decomposition to such a
      degree that it could be reflected as the function of GSH:urate. Results described
      here contribute to the understanding of the role of iron ions in catalyzing the
      conversion of NO into HNO/NO- and point to the role of uric acid not previously
      described.

PMID- 15566973
TI  - S-nitrosoglutathione incorporated in poly(ethylene glycol) matrix: potential use
      for topical nitric oxide delivery.
AB  - Incorporation of nitric oxide (NO) donors in non-toxic polymeric matrices can be
      a useful strategy for allowing topical NO delivery. We have incorporated the NO
      donor S-nitrosoglutathione (GSNO) into a liquid poly(ethylene glycol) (PEG)/H2O
      matrix through the S-nitrosation of GSH by a NO/O2 gas mixture. Kinetic
      measurements of GSNO decomposition associated with NO release were performed at
      25, 35, and 45 degrees C in the dark and under irradiation with UV/Vis light,
      lambda>480 nm and lambda=333 nm. NO release from the liquid matrix to the gas
      phase was confirmed by mass spectrometry. The PEG/H2O matrix stabilizes GSNO
      leading to expressive reductions in the initial rates of thermal and
      photochemical NO release, compared to aqueous GSNO solution. This matrix effect
      is assigned to diffusional constrains imposed on the escape of the NO and GS
      radicals formed in the solvent cage. This effect allows the storage of PEG-GSNO
      formulations for extended periods (more than 65 days at freezer) with negligible
      decomposition. PEG-GSNO formulation seems therefore to be applicable in topical
      NO delivery and GSNO displays potential as a percutaneous absorption enhancer.
      Moreover, the rate of NO release can be locally increased by irradiation with
      visible light.

PMID- 15566974
TI  - Relationship of asymmetric dimethylarginine to haemodialysis hypotension.
AB  - Hypotension is one of the major complications in patients undergoing
      haemodialysis (HD), that is well evident in patients defined as "hypotension
      prone." The mechanisms underlying the hypotensive episodes are not known. We
      carried out a clinical study on hypotension-prone HD patients to test the
      existence of a dysregulation in the nitric oxide (NO) generating pathway. Since
      asymmetric dimethylarginine (ADMA) is an endogenous compound which regulates NO
      synthesis, we measured its variation in plasma of stable-HD and hypotension-prone
      patients before, during, and at the end of HD. Before HD, the hypotension-prone
      patients have higher ADMA levels than stable-HD patients. The HD procedure
      significantly removes ADMA from plasma of stable-HD patients, while in the
      hypotension-prone ADMA levels are unchanged at the end of the HD. Moreover, in
      the hypotension-prone patients, during the hypotensive episode, a dramatic drop
      of ADMA levels is observed, followed by a rapid increase at the end of the HD.
      The symmetric dimethylarginine (SDMA), which has no effect on NO synthesis, is
      also high in plasma of both groups of HD patients compared to normal subjects,
      and in both groups its levels at the end of HD are significantly reduced. The
      hypotension-prone patients have basal TNF-alpha levels lower than the stable-HD
      groups, that significantly increase during the hypotensive episode. On the basis
      of these findings, we suggest that the hypotensive syndrome could be related to a
      dysregulation between ADMA metabolism and clearance due both to cytokines release
      and to an extremely fast ADMA clearance during HD, leading to an increase in NO
      blood levels.

PMID- 15566975
TI  - Potential and opportunities for use of recombinant lactic acid bacteria in human
      health.

PMID- 15566976
TI  - Novel aspects of signaling in Streptomyces development.

PMID- 15566977
TI  - Polysaccharide breakdown by anaerobic microorganisms inhabiting the Mammalian
      gut.

PMID- 15566978
TI  - Lincosamides: chemical structure, biosynthesis, mechanism of action, resistance,
      and applications.

PMID- 15566979
TI  - Ribosome engineering and secondary metabolite production.

PMID- 15566980
TI  - Developments in microbial methods for the treatment of dye effluents.

PMID- 15566981
TI  - Extracellular glycosyl hydrolases from clostridia.

PMID- 15566982
TI  - Kernel knowledge: smut of corn.

PMID- 15566983
TI  - Bacterial ACC deaminase and the alleviation of plant stress.

PMID- 15566984
TI  - Uses of Trichoderma spp. to alleviate or remediate soil and water pollution.

PMID- 15566985
TI  - Bacteriophage defense systems and strategies for lactic acid bacteria.

PMID- 15566986
TI  - Current issues in genetic toxicology testing for microbiologists.

PMID- 15566987
TI  - The Mexico Statement: strengthening health systems.

PMID- 15566988
TI  - Europe's health priorities for the world.

PMID- 15566989
TI  - The time has come for common ground on preventing sexual transmission of HIV.

PMID- 15566990
TI  - From a vicious circle to a virtuous circle: reinforcing strategies of risk,
      vulnerability, and impact reduction for HIV prevention.

PMID- 15566991
TI  - The imperative for family planning in ART therapy in Africa.

PMID- 15566992
TI  - Opioid substitution and HIV/AIDS treatment and prevention.

PMID- 15566993
TI  - Why AIDS in South Africa threatens stability and economic growth in other parts
      of Africa.

PMID- 15566994
TI  - Primum non nocere: prophylactic versus curative ibuprofen.

PMID- 15566995
TI  - Rescuing malaria treatment, or not?

PMID- 15566996
TI  - The James Lind Alliance: patients and clinicians should jointly identify their
      priorities for clinical trials.

PMID- 15566997
TI  - Statins for patients with type 2 diabetes.

PMID- 15566999
TI  - Statins for patients with type 2 diabetes.

PMID- 15567000
TI  - Cervical cerclage for prevention of preterm delivery in women with short cervix.

PMID- 15567001
TI  - Cervical cerclage for prevention of preterm delivery in women with short cervix.

PMID- 15567002
TI  - Stem-cell therapy: what dose should we use?

PMID- 15567004
TI  - Stem-cell therapy in amyotrophic lateral sclerosis.

PMID- 15567005
TI  - Nature of stem cell involved in fetomaternal microchimerism.

PMID- 15567006
TI  - Chemical danger.

PMID- 15567007
TI  - Chemical danger.

PMID- 15567008
TI  - An AIDS vaccine: no time to give up.

PMID- 15567009
TI  - Prophylactic ibuprofen versus placebo in very premature infants: a randomised,
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: Patent ductus arteriosus is a common complication of prematurity that
      frequently requires surgical or medical treatment. The benefit of prophylactic
      treatment by indometacin, a cyclo-oxygenase inhibitor, remains uncertain compared
      with curative treatment. This benefit could be improved with ibuprofen, another
      cyclo-oxygenase inhibitor with fewer adverse effects than indometacin on renal,
      mesenteric, and cerebral perfusion. We aimed to compare prophylactic and curative
      ibuprofen in the treatment of this abnormality in very premature infants.
      METHODS: We did a randomised controlled trial in infants younger than 28 weeks of
      gestation, who were randomly assigned to receive either three doses of ibuprofen
      or placebo within 6 h of birth. After day 3, symptomatic patent ductus arteriosus
      was treated first by open curative ibuprofen, then back-up indometacin, surgery,
      or both. The primary endpoint was need for surgical ligation. Analysis was per
      protocol. FINDINGS: The study was stopped prematurely after 135 enrollments
      because of three cases of severe pulmonary hypertension in the prophylactic
      group. 65 infants received prophylactic ibuprofen, and 66 received placebo.
      Prophylaxis reduced the need for surgical ligation from six (9%) to zero
      (p=0.03), and decreased the rate of severe intraventricular haemorrhage from 15
      (23%) to seven (11%) (p=0.10). However, survival was not improved (47 [71%]
      placebo vs 47 [72%] treatment, p=1.00), because of high frequency of adverse
      respiratory, renal, and digestive events. INTERPRETATION: In premature infants,
      prophylactic ibuprofen reduces the need for surgical ligation of patent ductus
      arteriosus, but does not reduce mortality or morbidity. Therefore, it should not
      be preferred to early curative ibuprofen.

PMID- 15567010
TI  - Prophylactic ibuprofen in premature infants: a multicentre, randomised, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Ibuprofen is used for treatment and prevention of patent ductus
      arteriosus in low-birthweight infants. Its effects on regional circulations
      differ from those of indometacin. Because prophylactic indometacin reduces the
      frequency of severe intraventricular haemorrhage and patent ductus arteriosus, we
      aimed to study the efficacy of early ibuprofen in reducing these outcomes in a
      double-blind, multicentre trial. METHODS: Within 6 h after birth, 415 low
      birthweight infants (gestational age <31 weeks) were randomly allocated ibuprofen
      lysine (10 mg/kg then two doses of 5 mg/kg after 24 h and 48 h) or placebo
      intravenously. The primary outcome was occurrence of severe intraventricular
      haemorrhage; secondary outcomes were occurrence of patent ductus arteriosus and
      possible adverse effects of ibuprofen. Analysis was by intention to treat.
      FINDINGS: 17 (8%) of 205 infants assigned ibuprofen and 18 (9%) of 210 assigned
      placebo developed severe intraventricular haemorrhage (relative risk 0.97 [95% CI
      0.51-1.82]). In 172 (84%) infants of the ibuprofen group, the ductus was closed
      on day 3 compared with 126 (60%) of the placebo group (relative risk 1.40 [1.23
      1.59]). No important differences in other outcomes or side-effects were noted;
      however, urine production was significantly lower on day 1 and concentration of
      creatinine in serum was significantly higher on day 3 after ibuprofen.
      INTERPRETATION: Ibuprofen prophylaxis in preterm infants does not reduce the
      frequency of intraventricular haemorrhage, but does decrease occurrence of patent
      ductus arteriosus.

PMID- 15567011
TI  - Combination treatments for uncomplicated falciparum malaria in Kampala, Uganda:
      randomised clinical trial.
AB  - BACKGROUND: Plasmodium falciparum resistance has rendered chloroquine monotherapy
      ineffective in much of Africa, but data on alternative regimens are limited. We
      compared chloroquine+sulfadoxine-pyrimethamine, amodiaquine+sulfadoxine
      pyrimethamine, and amodiaquine+artesunate for treatment of uncomplicated malaria
      in Kampala, Uganda. METHODS: Of 1017 consecutive patients aged 6 months to 10
      years with uncomplicated malaria who were screened, 418 were randomised to
      receive: chloroquine (25 mg/kg over 3 days) and sulfadoxine-pyrimethamine (25
      mg/kg sulfadoxine, 1.25 mg/kg pyrimethamine, single dose); amodiaquine (25 mg/kg
      over 3 days) and sulfadoxine-pyrimethamine; or amodiaquine and artesunate (4
      mg/kg daily for 3 days). Primary efficacy outcomes were 28-day clinical failure
      risks, adjusted and unadjusted by genotyping to distinguish new infection and
      recrudescence. The primary safety endpoint was incidence of serious adverse
      events during follow-up. Analysis was intention to treat and per protocol.
      FINDINGS: 18 patients were excluded before enrollment. Of those enrolled, 384 of
      400 (96%) were assigned an efficacy outcome and 396 (99%) were assessed for
      safety. Risk of 28-day clinical treatment failure was significantly higher with
      chloroquine+sulfadoxine-pyrimethamine (44/125 [35%]) than with
      amodiaquine+sulfadoxine-pyrimethamine (12/129 [9%]; risk difference 26% [95% CI
      16-36]; p<0.0001) or amodiaquine+artesunate (3/130 [2%]; 33% [24-42]; p<0.0001).
      The greater risk of clinical treatment failure with amodiaquine+sulfadoxine
      pyrimethamine was balanced by a lower risk of new infection, resulting in a
      similar need for retreatment over 28 days for amodiaquine+sulfadoxine
      pyrimethamine (17/129 [13%]) and amodiaquine+artesunate (16/130 [12%]; p=0.854).
      Serious adverse events were uncommon with all regimens. INTERPRETATION: Risk of
      treatment failure with chloroquine+sulfadoxine-pyrimethamine was unacceptably
      high. Combinations of amodiaquine and sulfadoxine-pyrimethamine or artesunate
      were significantly more efficacious, and each regimen could be an appropriate
      alternative for treatment of uncomplicated malaria in Africa.

PMID- 15567012
TI  - Operative correction of conjoined twins fused at head.

PMID- 15567013
TI  - Insomnia.
AB  - Effective management of insomnia begins with recognition and adequate assessment.
      Family doctors and other health care providers such as practice nurses and
      psychologists should routinely enquire about sleep habits as a component of
      overall health assessment. Identification and treatment of primary psychiatric
      disorders, medical conditions, circadian disorders, or specific physiological
      sleep disorders--eg, sleep apnoea and periodic limb movement disorder--are
      essential steps in management of insomnia. Conditioned aspects of insomnia can be
      primary (psychophysiological insomnia) or may complicate sleep disturbance owing
      to other causes. Approved hypnotic drugs have clearly been shown to improve
      subjective and objective sleep measures in various short-term situations. Despite
      widespread use of standard hypnotics and sedating antidepressants for chronic
      insomnia, their role for this indication still remains to be further defined by
      research evidence. Non-pharmacological treatments, particularly stimulus control
      and sleep restriction, are effective for conditioned aspects of insomnia and are
      associated with durable long-term improvement in sleep.

PMID- 15567014
TI  - Communicable diseases in complex emergencies: impact and challenges.
AB  - Communicable diseases, alone or in combination with malnutrition, account for
      most deaths in complex emergencies. Factors promoting disease transmission
      interact synergistically leading to high incidence rates of diarrhoea,
      respiratory infection, malaria, and measles. This excess morbidity and mortality
      is avoidable as effective interventions are available. Adequate shelter, water,
      food, and sanitation linked to effective case management, immunisation, health
      education, and disease surveillance are crucial. However, delivery mechanisms are
      often compromised by loss of health staff, damage to infrastructure, insecurity,
      and poor co-ordination. Although progress has been made in the control of
      specific communicable diseases in camp settings, complex emergencies affecting
      large geographical areas or entire countries pose a greater challenge. Available
      interventions need to be implemented more systematically in complex emergencies
      with higher levels of coordination between governments, UN agencies, and non
      governmental organisations. In addition, further research is needed to adapt and
      simplify interventions, and to explore novel diagnostics, vaccines, and
      therapies.

PMID- 15567015
TI  - Human resources for health: overcoming the crisis.
AB  - In this analysis of the global workforce, the Joint Learning Initiative-a
      consortium of more than 100 health leaders-proposes that mobilisation and
      strengthening of human resources for health, neglected yet critical, is central
      to combating health crises in some of the world's poorest countries and for
      building sustainable health systems in all countries. Nearly all countries are
      challenged by worker shortage, skill mix imbalance, maldistribution, negative
      work environment, and weak knowledge base. Especially in the poorest countries,
      the workforce is under assault by HIV/AIDS, out-migration, and inadequate
      investment. Effective country strategies should be backed by international
      reinforcement. Ultimately, the crisis in human resources is a shared problem
      requiring shared responsibility for cooperative action. Alliances for action are
      recommended to strengthen the performance of all existing actors while expanding
      space and energy for fresh actors.

PMID- 15567016
TI  - As a doctor you believe in facts, but as a manager you must believe in
      perceptions.

PMID- 15567017
TI  - Back pain and renal failure.

PMID- 15567019
TI  - Relations among relationships.

PMID- 15567020
TI  - Childhood abuse and neglect and adult intimate relationships: a prospective
      study.
AB  - OBJECTIVE: The present study extends prior research on childhood maltreatment and
      social functioning by examining the impact of early childhood physical abuse,
      sexual abuse, and neglect on rates of involvement in adult intimate relationships
      and relationship functioning. METHOD: Substantiated cases of child abuse and
      neglect from 1967 to 1971 were matched on gender, age, race, and approximate
      family class with non-abused and non-neglected children and followed
      prospectively into adulthood. Between 1989 and 1995, 1,196 participants (676
      abused and neglected and 520 controls) were administered a 2-hour in-person
      interview, including a psychiatric assessment and a variety of standardized
      rating scales. RESULTS: Male and female abuse and neglect victims reported higher
      rates of cohabitation, walking out, and divorce than controls. Abused and
      neglected females were also less likely than female controls to have positive
      perceptions of current romantic partners and to be sexually faithful.
      CONCLUSIONS: Although previous research on childhood maltreatment and adult
      intimate relationships has emphasized outcomes for female victims of childhood
      sexual abuse, present findings suggest that other forms of early maltreatment
      (physical abuse and neglect) also have a negative effect on both males' and
      females' ability to establish and maintain healthy intimate relationships in
      adulthood.

PMID- 15567021
TI  - Improving child maltreatment detection systems: a large-scale case study
      involving health, social services, and school professionals.
AB  - OBJECTIVES: The purpose of this 5-year study was to improve detection in two
      consecutive phases: (a) To close the gap between the number of identified cases
      and the actual number of cases of child abuse by increasing detection; and (b) To
      increase the possibility of a broader spectrum of detection. METHOD: The Balearic
      Islands (one of the Autonomous Communities of Spain, with 161,287 children under
      18 years old) was selected as the study area. Phase 1: front-line professionals
      (181) from all the health and social services agencies were trained in detection.
      Phase 2, school professionals (251) from all schools in the territory were also
      trained. The independent factor was the intervention provided to the
      professionals with training and support. A pre-post design was used over the
      area, divided in territories, in which the program was gradually implemented to
      provide within-territory and between-territories controls. RESULTS: Phase 1:
      Comparison before-after implementation of the program showed that detection was
      tripled in the Balearic Islands (from .58 to 1.77 per 1,000 children). An
      unplanned generalization effect was found, and post hoc analysis considering only
      the islands showed the expected increase. Phase 2: A subsequent increased
      detection rate was found in Child Protection Services cases 2.18 per 1,000. Of
      those new cases, 24.5% came from schools, after controlling for duplication.
      CONCLUSIONS: This detection system showed positive changes after training and
      supporting frontline health and social services professionals. However, these
      professionals only have occasional contacts with the child population. Therefore,
      to broaden the spectrum of detection and to reach more maltreated children, who
      are less likely to be visible to CPS, it is necessary to train and support school
      professionals because of the frequency of their contacts with children on an
      almost daily basis.

PMID- 15567022
TI  - Child sexual abuse in China: a study of adolescents in four provinces.
AB  - OBJECTIVE: Little is known about Child Sexual Abuse (CSA) in Chinese societies.
      This study examined CSA experiences and associations with demographic factors,
      self-reported health and risky behaviors among senior high school students in
      four provinces in central and northern China. METHOD: Students in four schools in
      Hubei, Henan, Hebei, and Beijing provinces participated in an anonymous, self
      completed questionnaire survey. From a total enrollment of 3,261 students in the
      target classes in years 11 and 12, 2,300 (70.5%) returned valid questionnaires.
      Mean age was 17.2 years. The questionnaire was adapted from prior CSA research in
      Australia and utilized standard scales for depression, self-esteem, and youth
      risk behavior. RESULTS: Prevalence of any unwanted sexual experience before the
      age of 16 years was higher among females (16.7%) than males (10.5%). Sexual
      penetration was rarely reported (1%), while 7% reported at least one type of
      physical contact abuse (female 8.9%, male 5.0%). Risk of any CSA was not
      associated with the existence of siblings (one-child vs. two- or more child
      families), rural/urban residence during childhood, or parental education. Males
      and females with CSA were more depressed and suicidal, and drank alcohol more
      often, than unaffected adolescents. Contact CSA was strongly associated with
      sexual intercourse (ever) for both males and females. Females with CSA were more
      likely than others to engage in anorexic and bulimic behaviors, while males with
      CSA were often involved in violence. CONCLUSION: Social norms for consensual
      sexual experiences differ between Eastern and Western societies. CSA experiences
      also differ, with substantially less penetrative and physical contact abuse in
      China. However, the psychological and behavioral profile of abused, young Chinese
      people, including the additional burden associated with contact abuse, is similar
      to that found in other cultures.

PMID- 15567023
TI  - Intention to participate in child sexual abuse prevention programs: a study of
      Chinese adults in Hong Kong.
AB  - OBJECTIVES: This study aimed to explore factors relating to intention to
      participate in community child sexual abuse (CSA) prevention programs among
      Chinese adults in Hong Kong. METHOD: A total of 1,606 Chinese adults (497 men and
      1,109 women) were individually interviewed about their intention to participate
      in community CSA prevention programs, endorsement of myths about CSA, their
      acquaintance with CSA victims, worry about CSA, and perceived prevalence of CSA.
      RESULTS: Among participants, nearly two-thirds believed CSA involved physical
      injuries of victims, 40% perceived boys as unlikely victims of CSA, and one-third
      were skeptical about children reports of CSA. About 24% of participants reported
      that they would definitely take part in CSA prevention programs. Participants who
      showed definite intention to participate in these programs endorsed fewer myths
      in relation to CSA, showed more worry about children being at risk of sexual
      abuse, perceived CSA as more prevalent and involving more physical injuries of
      victims, and were more likely to be women. CONCLUSIONS: Attention should be
      addressed to predisposing factors of adult participation in CSA prevention
      programs.

PMID- 15567024
TI  - Family of origin environments in two clinical samples of survivors of intra
      familial, extra-familial, and both types of sexual abuse.
AB  - OBJECTIVE: It has been suggested that survivors of ongoing childhood sexual abuse
      (CSA) tend to have been reared in ineffective family environments that render
      them particularly vulnerable to maltreatment and which foster psychological
      difficulties beyond those accounted for solely by their abuse. If this conjecture
      is valid, one would expect that the family of origin environments of CSA
      survivors would be disturbed whether their abuser was intra-familial or extra
      familial. To assess this hypothesis, two studies compared the childhood family of
      origin environments and supportive parenting characteristics of a clinical sample
      of women sexually abused by family members only (the intra-familial group), by
      non-family members only (the extra-familial group), and by both family and non
      family members (the "both" group). METHOD: Study 1 compared the three groups
      (total N = 213) using the Family Environment Scale (FES). Study 2 compared groups
      (total N = 86) on the positive parenting scales of the Exposure to Abusive and
      Supportive Environments Parenting Inventory (EASE-PI). RESULTS: In Study 1,
      multivariate analyses indicated significant differences on the independence,
      cohesion, and conflict subscales of the FES. Pairwise comparisons revealed that
      the extra-familial group reported significantly higher levels of family
      independence and lower levels of conflict than the other two groups. In addition,
      the extra-familial group reported higher levels of cohesion than the intra
      familial group. However, the effect sizes of these comparisons were extremely
      small. In Study 2, multivariate analyses revealed no group differences on the
      EASE-PI scales. CONCLUSIONS: Low effect sizes on the three significant FES
      scales, non-significance on the remaining seven FES scales, and non-significance
      on the EASE-PI scales suggest that there is considerable similarity in the family
      of origin environments of adult female CSA survivors seeking therapy regardless
      of whether their perpetrators were family members, non-family members, or both
      family and non-family members.

PMID- 15567025
TI  - Many ways of telling: expanding conceptualizations of child sexual abuse
      disclosure.
AB  - OBJECTIVE: The aim of this study was to explore influences that inhibit or
      promote child sexual abuse (CSA) disclosure. METHOD: Face-to-face in-depth
      interviews of 24 female and male survivors of CSA were conducted, using the Long
      Interview method to trace disclosure processes. Verbatim transcriptions of the
      interviews were analyzed by hand and by using a computerized data analysis system
      (N*Vivo). The results of this investigation identified several patterns of
      disclosure. Prolonged engagement, persistent observation, negative case analysis,
      and peer debriefing were among the techniques used to ensure the trustworthiness
      of data. RESULTS: Through analysis of the interview data, previously undefined
      dimensions of disclosure emerged. First, three frequently used categories of
      'accidental, purposeful, and prompted/elicited' disclosure types accounted for
      42% of disclosure patterns in the study sample. However, over half the disclosure
      patterns described by research participants did not fit these previously
      established definitions. Results of the study facilitated expanding
      conceptualization of additional disclosure patterns to include behavioral and
      indirect verbal attempts, disclosures intentionally withheld, and disclosures
      triggered by recovered memories. CONCLUSIONS: The author concludes that these
      supplementary definitions integrate complex facets of disclosure derived within
      the context of human development, memory and environmental influences. This
      expanded conceptualization provides professionals with a broader framework to
      understand and respond to child victims and adult survivor's disclosures more
      effectively.

PMID- 15567026
TI  - African-American women who use crack cocaine: a comparison of mothers who live
      with and have been separated from their children.
AB  - OBJECTIVE: This study examined factors that influenced caregiver status for
      African-American mothers who use crack cocaine but are not receiving drug
      treatment and participated in an HIV prevention study in North Carolina. METHOD:
      Caregiver mothers who were living with at least one of their children at intake
      (n = 257) were compared with non-Caregivers who were separated from all of their
      children (n = 378). Bivariate analyses and logistic regression were used to
      compare these mothers at intake on current drug use, risky sex practices,
      psychological symptoms, victimization, and aggression. RESULTS: Compared with
      Caregiver mothers, non-Caregivers reported higher frequencies of drug use, risky
      sex practices, psychological distress, and victimization experiences. Caregiver
      mothers were more likely than non-Caregiver mothers to have health insurance, but
      were less likely to have received drug treatment. Logistic regression found that
      non-Caregiver mothers were significantly more likely than Caregiver mothers to be
      older, to have been physically abused as children, to trade sex more frequently,
      to be homeless, and to have no health insurance. Recent crack use, psychological
      symptoms, and victimization were not significantly related to caregiver status.
      CONCLUSIONS: Findings that socio-environmental factors were more strongly
      associated with caregiver status than crack use underscore the importance of
      contextual issues such as housing, victimization history, and resources in
      serving maternal crack users. Community outreach and interventions that engage
      mothers who use drugs and live with their children may be more effective
      strategies than formal office-based services to link mothers who use crack and
      their children to needed drug treatment and family and child services.

PMID- 15567027
TI  - Complete nucleotide sequence of the hirame rhabdovirus, a pathogen of marine
      fish.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) derived clones were
      constructed for the hirame rhabdovirus (HIRRV) CA-9703 strain from Korea, and the
      DNA was sequenced. The 3'-end of genomic RNA was cloned by poly(A)-tailing of the
      genomic RNA before reverse transcription, and the 5'-end of the genome was cloned
      by poly(G)- or poly(C)-tailing of the first strand, followed by PCR. The
      remainder of the genomic DNA was cloned by reverse transcription-polymerase chain
      reaction using primers that were based on the published rhabdovirus sequences.
      The complete genome of HIRRV CA-9703 strain comprises 11,034 nucleotides and
      encodes six genes in the order of: 3'-leader, N, P, M, G, NV, L, and 5'-trailer.
      These genes are separated by conserved sequences or gene junctions, with one
      nucleotide gene spacers. The first 16 of the 19 nucleotides at the ends of the
      HIRRV genome are complementary, and the first four nucleotides at the 3'-ends of
      the HIRRV, infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic
      septicemia virus (VHSV), and snakehead rhabdovirus (SHRV) genomes are identical.
      The HIRRV proteins share the highest amino acid sequence homology (ranging from
      72% to 92%) with the proteins of IHNV, of all the known fish rhabdoviruses, and
      the highest sequence homology with respect to the L protein was shared among
      HIRRV, IHNV, VHSV, and SHRV. Although there were differences in the degrees of
      relatedness, phylogenetic trees that were derived from multiple sequence
      alignments of the rhabdovirus proteins showed similar patterns of relationship
      among these viruses, in which fish Novirhabdoviruses formed a separate clade from
      spring viremia of carp virus (SVCV), unassigned fish rhabdovirus that was closer
      to mammalian rhabdoviruses.

PMID- 15567028
TI  - Sequence polymorphism in the E3 7.7K ORF of subspecies B1 human adenoviruses.
AB  - Sequences corresponding to the 7.7K open-reading frame (ORF) of the E3 region of
      subspecies B1 adenoviruses (Ads) were compared with prototype strains of Ad3,
      Ad7, Ad16, Ad21, and Ad50 and field isolates representing a variety of genome
      restriction types of Ad3 and Ad7 to better assess the extent of genetic variation
      in this intriguing region of the viral genome encoding a product whose function
      is still unknown. Alignment of 55 species B1 Ad sequences revealed a marked
      polymorphism in the 7.7K ORF and allowed the identification of eight distinct
      sequence profiles (SPs) characterized by (1) deletions that retain or change the
      reading frame, (2) single-base mutations (SBMs) that change the start codon (ATG
      to ATT or ATC), and (3) other SBMs. mRNAs of expected size for the observed
      sequence polymorphisms were identified by RT-PCR from DNAse I-treated total RNA
      extracts of infected cells. Predicted proteins ranged from 0 to 94 amino acids
      corresponding to molecular masses of 0-11 K. Together with the hypervariable
      regions of the hexon gene, the E3 7.7K ORF appears to be another area of the Ad
      genome in which genetic diversity may be generated by illegitimate recombination.

PMID- 15567029
TI  - Cys254 and Cys49/Cys87of simian virus 40 Vp1 are essential in formation of
      infectious virions.
AB  - The SV40 capsid is composed of pentameric capsomeres of Vp1. We have previously
      shown that disulfide linkages at Vp1 Cys9, Cys104, and Cys207 are essential in
      formation of infectious virions. Here, the role of the remaining four cysteines
      was explored. Single, double, and quadruple cys --> ser mutant genomes at Vp1
      Cys49, Cys87, Cys254, and Cys267 codons were generated and transfected into CV-1
      cells. The quadruple mutant Vp1 continued to localize to the nucleus and to bind
      DNA, but resulted in no plaques. SV40Vp1.Cys254 was the only single mutant with
      complete defect in plaque formation. The double mutant at Vp1.Cys49.Cys87 showed
      complete defect in plaque formation, while single mutants at the two residues
      resulted in plaques, suggesting a cumulative effect. All mutants defective in
      plaque formation continued to localize viral proteins in the nucleus. Taken
      together, our results suggest that Cys254 and the Cys49/Cys87 combination are
      essential in late stages of infectious virion formation.

PMID- 15567030
TI  - Adaptability costs in immune escape variants of vesicular stomatitis virus.
AB  - We have used vesicular stomatitis virus (VSV) to determine the cost of antiserum
      resistance during escape from a polyclonal immune response. Replication of VSV in
      the presence of polyclonal antiserum resulted in the selection of antibody-escape
      mutants, as shown by increased fitness in the presence of antiserum and by
      increased resistance to neutralization. However, resistance came at a cost of
      overall fitness loss in the BHK-21 host cells. Sequencing of the surface G
      glycoprotein showed that two to four mutations were fixed in each population,
      most of which mapped in the A1 and A2 antigenic sites. Selected resistant
      populations were passaged as large populations in BHK-21 cells under constant
      conditions, which would normally lead to fitness increases. Nevertheless, many of
      the populations showed little or no sign of recovery, although the resistant
      phenotype was maintained. These results suggest that while antiserum resistance
      can develop, it may come at a cost in fitness and further limitations in the
      adaptability of the populations.

PMID- 15567031
TI  - Replication of Theiler's murine encephalomyelitis virus in Xenopus laevis
      oocytes.
AB  - Xenopus laevis oocytes can be used as an alternative system to study replication
      of Theiler's murine encephalomyelitis virus (TMEV). We have shown that transcript
      RNA, containing full-length viral genome, can be directly used to programme the
      oocytes. In the programmed oocytes, there is correct viral translation,
      polyprotein processing and assembly of capsid proteins leading to the production
      of infectious TMEV. The vast majority of de novo synthesised virions were found
      in the medium in which the programmed oocytes were incubated and not in the
      oocytes.

PMID- 15567032
TI  - Nucleotide sequence of a mitochondrial RNA virus from the plant pathogenic
      fungus, Helicobasidium mompa Tanaka.
AB  - A double-stranded (ds) RNA (2411 bp) from a strain V18 of the violet root rot
      basidiomycetous fungus, Helicobasidium mompa was sequenced. Using the fungal
      mitochondrial genetic code in which UGA codes for tryptophan, the positive strand
      of V18 dsRNA was found to contain a long open-reading frame with the potential to
      encode a protein of 700 amino acids (molecular mass 79,805 Da), including
      conserved motifs characteristic of RNA-dependent RNA polymerase (RDRP). This
      putative RDRP was shown to be related to putative RDRPs of several fungal
      mitochondrial viruses. It is proposed that V18 dsRNA is assigned to the genus
      Mitovirus in the family Narnaviridae and designated as H. mompa mitovirus 1-18
      (HmMV1-18). Like other mitoviruses, HmMV1-18 RNA can be folded into potentially
      stable stem-loop structures at both the 5'- and 3'-termini, and both terminal
      sequences have inverted complementarity with the potential to form panhandle
      structure. BLAST analysis indicates that the RDRP encoded by HmMV1-18 is more
      closely related to those encoded by mitochondrial viruses of some ascomycetes
      than to that of the unassigned RsM2-1A1 dsRNA in the basidiomycetous Rhizoctonia
      solani. HmMV1-18 is the first member of the genus Mitovirus from basidiomycete
      fungi.

PMID- 15567033
TI  - Ostreid herpesvirus 1 (OsHV-1) detection among three successive generations of
      Pacific oysters (Crassostrea gigas).
AB  - Ostreid Herpesvirus 1 (OsHV-1) was likely detected in Pacific oysters,
      Crassostrea gigas, at different stages of development. Viral infections were
      associated with high mortality rates in the spat and larvae. Furthermore, the
      persistance of OsHV-1 in asymptomatic adults was demonstrated by detection of
      viral DNA and proteins. In the present study, three successive generations of C.
      gigas (G0 and G1 parental oysters, G1 and G2 larvae) were screened for OsHV-1 by
      PCR. Viral DNA was detected in 2-day-old larvae, indicating that infection may
      take place at very early stages. Although results strengthen the hypothesis of a
      vertical transmission, it was not possible to predict the issue of a particular
      type of cross. Indeed, the detection of viral DNA in parental oysters did not
      systematically correspond to a productive infection or result in a successful
      transmission to the progeny. However, the infective status of the parents
      appeared to have an influence on both the infection and the survival rates of the
      progeny. Crosses involving an OsHV-1 infected male and a non-infected female
      resulted in hatching and larval survival rates statistically lower than those
      observed in the other types of cross. These results suggest that OsHV-1-infected
      females may transmit to their offspring some kind of protection or resistance
      against viral infection.

PMID- 15567034
TI  - Identification and enzymatic characterization of NS2B-NS3 protease of Alkhurma
      virus, a class-4 flavivirus.
AB  - Alkhurma virus (ALKV) is a recently discovered class-4 flavivirus that was
      responsible for several cases of severe haemorrhagic fever in humans in Saudi
      Arabia. It has been shown for other flaviviruses that processing of the viral
      polyprotein is partly due to the virus-encoded NS2B/NS3 trypsin-like serine
      protease. As the viral proteinase plays a critical role in the virus replication
      cycle, it represents one of the main targets for antiviral therapy against
      members of the Flavivirus genus. We report here on the identification of the ALKV
      NS2B and NS3 domains and the expression and purification of a catalytically
      active viral protease as a hexahistidine recombinant protein. Its enzymatic
      properties were characterized in vitro using a para-nitroanilide substrate. This
      constitutes the first characterization of the proteinase from a class-4
      flavivirus. Our results indicate that the association of NS3 with a short segment
      of NS2B is necessary and sufficient for protease activity. The developed system
      could help to identify or design inhibitors potentially active as antiviral drugs
      against ALKV and other pathogenic flaviviruses.

PMID- 15567035
TI  - Molecular analysis of the proviral DNA of equine infectious anemia virus in mules
      in Greece.
AB  - Molecular analysis of the regulatory and structurally important genetic segments
      of equine infectious anemia virus (EIAV) in mules is presented. We have
      previously reported clinicopathological and laboratory findings in mules infected
      with EIAV, both naturally and after experimental inoculation. In this study the
      fragment coding for integrase, gp90, tat and the fusion domain of gp45 of the
      proviral genome from these animals was sequenced and compared with one another
      and with that of EIAV strains already published in the literature. Significant
      variations were observed mainly in the sequences of the gp90 surface protein. In
      the two wild type sequences, there were substitutions in the V5 hypervariable
      domain of this protein. In the sequences of the experimentally inoculated animals
      and the donor strain, variations were due to insertions/duplications in the V3
      principal neutralizing domain (PND) and substitutions in the V5 hypervariable
      domain. Finally, when compared with the already published strains, the wild type
      sequences had single amino acid substitutions across the whole protein and
      multiple substitutions in the V4-V6 variable domains. In general, the two Greek
      wild type sequences were closer to two of the American strains (WSU5 and
      Massachusetts), than to the two Japanese (V26 and V70) or the third American
      strain (Wyoming_wi) used in this study.

PMID- 15567036
TI  - cDNA microarray analysis to compare HCV subgenomic replicon cells with their
      cured cells.
AB  - The hepatitis C virus (HCV) replicon system carrying autonomously replicating HCV
      subgenomic RNA in human hepatocyte cells is a potent tool for basic studies of
      HCV, such as viral replication and drug development. Recently, we developed two
      HCV subgenomic replicons (50-1 and 1B-2R1) derived from two HCV strains, 1B-1 and
      1B-2, respectively. Since the expression of HCV proteins is thought to affect the
      host cells' gene expression profiles, we attempted to identify target genes of
      HCV proteins using microarray analysis (9970 genes) by comparing 50-1 and 1B-2R1
      replicon cells with their "cured cells", from which the replicons had been
      eliminated by prolonged treatment with interferon-alpha. The results showed that
      HCV replicons could have a variety of expression profiles in human hepatocytes.
      The results also showed that 2 and 6 genes were commonly up-regulated (more than
      2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both 50-1
      and 1B-2R1 replicon cells compared with their cured cells. The differential
      expression profiles of genes selected by the microarray analysis were confirmed
      with standard RT-PCR and real-time LightCycler PCR. It was noteworthy that the
      commonly down-regulated genes contained large multifunctional proteases 2 and 7,
      which are known as catalytic subunits of immunoproteasome, and serine proteinase
      inhibitor clade C. Our microarray analysis demonstrated that HCV subgenomic
      replicons can change the gene expression profiles of host cells, and it allowed
      us to compile the first list of genes that the replicons transcriptionally
      regulate.

PMID- 15567037
TI  - Comparison of the full-length genome sequence of avian metapneumovirus subtype C
      with other paramyxoviruses.
AB  - We determined the nucleotide (nt) sequence of the small hydrophobic (SH),
      attachment glycoprotein (G), and RNA polymerase (L) genes, plus the leader and
      trailer regions of the Colorado strain of Avian metapneumovirus subtype C
      (aMPV/C) in order to complete the genome sequencing. The complete genome
      comprised of 13,134 nucleotides, with a 40 nt leader at its 3' end and a 45 nt
      trailer at its 5' end. The aMPV/C L gene was the largest with 6173 nt and
      consisting of a single open reading frame encoding a 2005 amino acids (aa)
      protein. Comparison of the aMPV/C SH, G, and L nt and predicted aa sequences with
      those of Human metapneumoviruses (hMPV) revealed higher nt and aa sequence
      identities than the sequence identities between the aMPV subtypes A, B, C, and D,
      supporting earlier finding that aMPV/C was closer evolutionary to hMPV than the
      other aMPV subtypes.

PMID- 15567038
TI  - SARS-coronavirus replication in human peripheral monocytes/macrophages.
AB  - A novel coronavirus (CoV) has been described in association with cases of severe
      acute respiratory syndrome (SARS). The virus, SARS-CoV, differs from the
      previously described human coronaviruses, 229E and OC43. 229E was previously
      shown to productively infect human monocytes/macrophages, whereas OC43 poorly
      infected the cells. In this study, we examined whether SARS-CoV could
      productively infect purified monocytes/macrophages (PM) derived from human donor
      cells. Unlike 229E-infected cells, which produced viral titers of 10(3.5) to
      10(6)TCID50/ml, SARS-CoV replicated poorly in PM, producing titers of 10(1.75) to
      10(2)TCID50/ml. This finding was similar to results reported for OC43-infected
      cells, with titers ranging from 10(1.2) to 10(2.7)TCID50/ml. Of interest, SARS
      CoV proteins were detected only in PM that did not produce significant amounts of
      interferon (IFN)-alpha, and in one such case, preliminary electron microscope
      studies demonstrated that SARS-CoV-like particles could enter the cells, possibly
      via phagocytosis. These results suggest that SARS-CoV, like human CoV OC43,
      poorly infects human PM, and production of IFN-alpha by these cells further
      limits the infection. Given the importance of monocytes/macrophages to the immune
      response, it is possible that their infection by SARS-CoV and alteration of this
      infection by IFN-alpha may be important to the course of the infection in humans.

PMID- 15567039
TI  - Transcriptional response of avian cells to infection with Newcastle disease
      virus.
AB  - Newcastle disease virus (NDV) causes widespread disease in poultry and wild-birds
      throughout the world. cDNA microarray analysis was used to examine the effect of
      NDV infection on host cell transcription. The results show that NDV infection
      causes an apparent suppression of the interferon response genes during the early
      stages of infection. In addition, the results reveal transcriptional silencing of
      cytoskeletal proteins such as the alpha, beta, and gamma types of actin, and a
      downregulation of the thioredoxin gene, a likely mediator of apoptosis with
      possible implications in NDV pathogenesis. Comparative analyses show that a
      majority of genes that were transcriptionally regulated during infection with
      another common respiratory pathogen of poultry, the avian pneumovirus, remained
      unaltered during NDV infection, suggesting that even phylogenetically related
      viruses elicit unique or "signature" patterns of host transcriptional profiles
      during infection of host cells.

PMID- 15567040
TI  - An interlaboratory comparison of immunohistochemistry and PCR methods for
      detection of Neospora caninum in bovine foetal tissues.
AB  - Seven European laboratories contributed to a multi-centre evaluation of detection
      techniques for Neospora caninum in bovine foetuses. Six laboratories participated
      in immunohistochemistry (IHC) testing. All seven laboratories participated in PCR
      testing, but the results from one laboratory were not included in the analysis,
      because of contamination problems in the preparation of the samples. A coded
      panel of tissue sections from 36 infected and non-infected foetuses was used to
      evaluate the IHC detection of parasites. A coded panel consisting of 44
      homogenized foetal brain samples from natural bovine abortion cases and 32 spiked
      samples were used to evaluate the PCR methods. Inclusion of a duplicate dilution
      series of spiked samples was used to evaluate detection limits and repeatability.
      IHC methods had a relatively low sensitivity, but a high specificity. There was
      considerable variation in IHC results between participating laboratories, which
      may be partly explained by examination practices that depended on the experience
      of the operator. In addition, the use of different antibody reagents, different
      antibody dilutions, and different enzymatic treatments of tissues may have
      contributed to the observed variation. PCR methods generally had a higher
      sensitivity than IHC methods and also a high specificity. The agreement between
      the majority scores of IHC and PCR methods was low. False positive PCR results
      indicated contamination problems in some instances. Agreement between the PCR
      results of the various laboratories was better, compared with the IHC results.
      There appeared to be no clear relationship between the PCR format (i.e. single or
      nested) and diagnostic sensitivity. Consequently, an improvement of diagnostic
      performance of PCR might possibly be achieved by optimizing DNA extraction
      methods.

PMID- 15567041
TI  - A comparative evaluation of parasitological, serological and DNA amplification
      methods for diagnosis of natural Trypanosoma evansi infection in camels.
AB  - A representative number of 217 camels (Camelus dromedarius) from different areas
      of western Rajasthan State, India, were examined from July 2002 to May 2003 for
      Trypanosoma evansi infection. The tests used were parasitological (wet blood
      film, WBF; stained thin blood smear, TBS), immunodiagnostic (double antibody
      sandwich enzyme linked immunosorbent assay for antigen detection, Ag-ELISA), and
      DNA amplification by polymerase chain reaction (PCR). These techniques were
      compared and the best efficiency was found for the last named (PCR). A prevalence
      of T. evansi infection was detected in 17.05, 9.67, 4.60 and 4.14% by PCR, Ag
      ELISA, TBS and WBF with a sensitivity of 100, 56.75, 27.02 and 24.32%,
      respectively. PCR revealed a specific 227bp band in positive samples. The
      intensity of PCR bands was variable in different test samples depending upon the
      level of infection in the test samples. The history of intermittent fever,
      emaciation, oedema, poor body condition significantly correlated with positive
      serological status in ELISA as well as trypanosome DNA detection by PCR.

PMID- 15567042
TI  - Bermudagrass management in the Southern Piedmont USA. V: Gastrointestinal
      parasite control in cattle.
AB  - Parasite-free pastures would improve cattle health and performance, resulting in
      possible economic return to producers. Our objective was to determine the effect
      of a single series of anthelmintic treatment of steers prior to stocking on
      Coastal bermudagrass pastures, during five consecutive summers, on the parasite
      burden in cattle. The site for this experiment had been conventionally cropped
      for several decades, with no exposure to cattle, and would be expected to be
      relatively free of nematode larvae. The experimental design was a randomized
      complete block (landscape features) with a split plot arrangement of treatments
      where main plots were pasture fertilization treatments (mineral, clover plus
      mineral, and broiler litter) and split plots were low and high forage mass.
      Anthelmintic treatment included pour-on ivermectin on day -21, albendazole on day
      -7, and injectable ivermectin 48 h prior to stocking of pastures, with the cattle
      remaining in drylot during the 48-h period prior to being placed on the
      experimental paddocks. All steers received only one series of treatments during
      any given year. Yearling Angus steers (Bos taurus) were managed in a put-and-take
      grazing system with three "tester" steers assigned to each paddock and "grazer"
      steers added or removed at 28-day intervals. From 1994 to 1998, steers grazed the
      paddocks for a 140-day period from mid May until early October each year. Fecal
      samples for worm egg counts were obtained on day 0 and at 28-day intervals,
      thereafter. On all sampling days after day 0, samples were obtained only from
      tester animals. Over the 5-year period, the mean eggs per gram of feces (epg)
      gradually increased from 0 (following treatment) to a mean of 2.2 (range from 0.7
      to 3.0) by the end of the grazing season (the last sampling date) in October.
      Although the epg were not zero, they were below threshold levels that would allow
      development of a parasite burden in cattle. In traditional management systems,
      cattle graze parasite-contaminated pastures; therefore, parasites negatively
      impact growth and productivity throughout the entire grazing period. Periodic
      anthelmintic treatments simply give a temporary reprieve from those parasitic
      infections. Conceptually, using the current grazing system, it should be possible
      to maintain these pastures in a parasite-free status indefinitely; however, from
      a drug resistance perspective, it would be most applicable in sod-based rotation
      systems where cattle graze from two to five years before land is returned to row
      crops. By removing the effect of parasites, cattle can grow without the
      physiological constraints that gastrointestinal parasites place on appetite,
      digestion, nutrient utilization, and general well being.

PMID- 15567043
TI  - The risks of translocating wildlife. Pathogenic infection with Theileria sp. and
      Elaeophora elaphi in an imported red deer.
AB  - It is well known that the translocation of wild animals poses risks of the
      introduction of pathogens into populations, and regulations and recommendations
      regarding quarantine and screening protocols for wild animals do exist. Less is
      known about the infection of imported animals with local endemic pathogens. A red
      deer stag that had been imported from Germany was found recumbent and died from
      hemolytic anaemia and a process of exertional myopathy. Infection with Theileria
      sp. was detected in thin blood smears and confirmed by PCR and sequencing. In
      addition, massive parasitation by Elaeophora elaphi, a parasite endemic to
      Iberian red deer, was detected. Sequence comparison between the 18S rRNA gene
      sequence determined that the Theileria strain involved in this case had a 99.7%
      identity with a Theileria sp. strain obtained from sika-deer, and 95.3% identity
      with T. cervi. Using sequence distance analysis, the strain from red deer grouped
      with isolates from Cervus spp. as opposed to isolates from Odocoileus spp. and
      bovines. Both detected parasites are of little pathogenicity to local red deer,
      but were pathogenic for the imported red deer from Northern Europe. This case
      demonstrates that local endemic pathogens may pose naive translocated animals at
      risk, and illustrates the need for thorough examination and planification of
      translocation protocols.

PMID- 15567044
TI  - Observations of the sheath extension of the third stage, infective larvae of
      Trichostrongylus rugatus.
AB  - The length of the sheath extension of third stage (L(3)), infective larvae of
      Trichostrongylus rugatus is reported. The total length and length of the sheath
      extension of L(3) recovered from the faeces of sheep originating from two
      localities in South Australia were measured. The total length of larvae was 615
      722 microm and the length of the sheath extension was 46-56 microm (mean 51.5).
      The larvae of T. rugatus comprised up to 72% of the larvae recovered. Worm free
      sheep were infected with larvae from the two localities and L(3) were recovered
      following culture of faeces from these experimentally infected animals. L(3)
      measured 640-746 microm in total length with a sheath extension of 46-56 microm
      (mean 51.4). Adult nematodes recovered from gastro-intestinal tracts were
      identified as T. rugatus. The length of the sheath extension used in conjunction
      with the total length is a characteristic that enables confident differentiation
      of infective larvae of T. rugatus from other Trichostrongylus species infecting
      sheep in southern Australia and Haemonchus contortus.

PMID- 15567045
TI  - The relationship among voice onset, voice quality, and fundamental frequency: a
      dynamical perspective.
AB  - In dynamical motor theory, skill acquisition occurs as a modification of
      preexisting coordination patterns or attractor states. The purpose of this study
      was to assess how different levels of voice onset, voice quality, and fundamental
      frequency (F(0)) combine to form the attractor states common to voice motor
      control. Three levels of voice onset (glottal, simultaneous, and breathy), voice
      quality (modal speech, mixed, and falsetto), and fundamental frequency (low, mid,
      and high) were manipulated by vocally untrained, female subjects. Percent correct
      of acquisition trials and self-report of effort were used as measures of stable
      phonations indicative of an attractor state. Using intensity as a covariate, the
      results provided support for two of the three predicted triads representing
      attractor states in female speakers: (1) glottal onset/modal speech quality/low
      F(0); and (2) breathy onset/falsetto quality/high F(0). The results of this study
      suggest that certain parameters of voice motor control, such as onset, quality,
      and F(0), exist as part of a dynamical system that can be identified and
      manipulated in voice motor acquisition and learning.

PMID- 15567046
TI  - Vocal stability in functional dysphonic versus healthy voices at different times
      of voice loading.
AB  - Functional (nonorganic) dysphonia is often characterized by vocal instability.
      The purpose of the prospective study was to examine whether there is a difference
      in vocal instability of functional dysphonic voices compared with healthy ones,
      this means whether electroglottographic perturbation values differ (1) between
      healthy and dysphonic voices and (2) between two subgroups of the dysphponic
      voices (hypertonic and hypotonic dysphonic voices). Twenty-three patients with
      hypertonic functional dysphonia, 9 with hypotonic functional dysphonia and 31
      healthy nonsmokers, were each examined electroglottographically before (Ex 1),
      immediately after (Ex 2), and 1 hour after (Ex 3) voice loading. Perturbations of
      frequency, amplitude, quasi-open-quotient, and contact-index were calculated from
      the EGG signal. At all three times of examination, hypertonic dysphonic voices
      showed higher perturbations than healthy voices, and they had higher
      perturbations than hypotonic dysphonic voices before and 1 hour after voice
      loading. Hypotonic dysphonic voices showed higher perturbations than healthy
      voices only 1 hour after voice loading. Voice loading induced different reactions
      in dysphonic voices: Some voices showed increased perturbations, and others
      exhibited normal or even decreased perturbation immediately after voice loading.
      Examination of electroglottographic-derived perturbations immediately after voice
      loading seems not to be useful. Differentiation of hypertonic and hypotonic
      dysphonic voices was possible with an estimated sensitivity of 88.9% and a
      specificity of 87.0% by using the sum of the amplitude-perturbation and the quasi
      open-quotient-perturbation measured before voice loading.

PMID- 15567047
TI  - Perceived phonatory effort and phonation threshold pressure across a prolonged
      voice loading task: a study of vocal fatigue.
AB  - Although the problem of vocal fatigue is not uncommon in people with voice
      disorders, research on objective quantifiable indicators of vocal fatigue is
      limited. It has been suggested that a speaker's perception of increased phonatory
      effort associated with periods of prolonged voice use is related to increased
      lung pressure required to initiate and sustain phonation. The purpose of this
      study was to examine the relationship among perceived phonatory effort (PPE),
      which was used as a subjective index of vocal fatigue, and phonation threshold
      pressure (PTP), a quantifiable measure defined as the minimal lung pressure
      required to initiate and sustain vocal fold oscillation. PTP and PPE were
      recorded before, during, and after five adult male and five adult female speakers
      engaged in a prolonged oral reading task designed to induce vocal fatigue. The
      results supported a direct, moderately strong relationship between PTP and PPE,
      particularly when PTP was measured during speech produced at comfortable and low
      speaking pitch levels. No gender effects were found. PTP returned to baseline
      levels within 1 hour after the fatiguing task. PPE returned to baseline within 1
      day. The data support the use of PTP as an objective index of vocal fatigue.

PMID- 15567048
TI  - Outcome of laryngeal manual therapy in four Dutch adults with persistent moderate
      to-severe vocal hyperfunction: a pilot study.
AB  - A relatively new management strategy for the treatment of voice disorders is the
      use of laryngeal manual therapy. The main purpose of the present pilot study is
      to document the outcome of vocal quality after a well-defined laryngeal manual
      therapy (LMT) program. Four Dutch professional voice users with a persistent
      moderate or severe muscle tension dysphonia were studied pretreatment (1 week
      before LMT) and posttreatment (1 week) after completion of manual therapy (25
      sessions). These subjects had received several months of traditional voice
      therapy, without any success. To measure and compare, the effect of LMT objective
      and subjective assessment techniques were used. Perceptual voice assessment
      included a perceptual rating of the voice using the GRBAS scale. Furthermore, the
      vocal quality in this population was modeled by means of the Dysphonia Severity
      Index (DSI). All of the subjects selected for LMT showed improvement in
      perceptual vocal quality and DSI values. As the DSI is a weighted variable
      including aerodynamic and acoustic measures, small improvements (closer to 5) are
      very indicative of vocal quality improvement. The use of LMT in professional
      voice users with persistent moderate-to-severe muscle tension dysphonia,
      especially in some subjects who have not responded to traditional voice therapy,
      is supported by this pilot study.

PMID- 15567049
TI  - Effects of HearFones on speaking and singing voice quality.
AB  - HearFones (HF) have been designed to enhance auditory feedback during phonation.
      This study investigated the effects of HF (1) on sound perceivable by the
      subject, (2) on voice quality in reading and singing, and (3) on voice production
      in speech and singing at the same pitch and sound level. Test 1: Text reading was
      recorded with two identical microphones in the ears of a subject. One ear was
      covered with HF, and the other was free. Four subjects attended this test. Tests
      2 and 3: A reading sample was recorded from 13 subjects and a song from 12
      subjects without and with HF on. Test 4: Six females repeated [pa:p:a] in
      speaking and singing modes without and with HF on same pitch and sound level.
      Long-term average spectra were made (Tests 1-3), and formant frequencies,
      fundamental frequency, and sound level were measured (Tests 2 and 3). Subglottic
      pressure was estimated from oral pressure in [p], and simultaneously
      electroglottography (EGG) was registered during voicing on [a:] (Test 4). Voice
      quality in speech and singing was evaluated by three professional voice trainers
      (Tests 2-4). HF seemed to enhance sound perceivable at the whole range studied (0
      8 kHz), with the greatest enhancement (up to ca 25 dB) being at 1-3 kHz and at 4
      7 kHz. The subjects tended to decrease loudness with HF (when sound level was not
      being monitored). In more than half of the cases, voice quality was evaluated
      "less strained" and "better controlled" with HF. When pitch and loudness were
      constant, no clear differences were heard but closed quotient of the EGG signal
      was higher and the signal more skewed, suggesting a better glottal closure and/or
      diminished activity of the thyroarytenoid muscle.

PMID- 15567050
TI  - Fragments of a Greek Trilogy: impact on phonation.
AB  - This study documents the vocal characteristics of an actor before and after a
      series of eight performances involving extended voice use. The hypothesis was
      that this type of extended voice use would result in symptoms of vocal abuse and
      that damage to the actor's voice would be evident in measures made after the
      performance series. Three pre-performance and three post-performance speech
      samples were gathered and analyzed using the CSL and Visipitch II. Measurements
      taken included maximum phonational range; maximum sustained phonation;
      fundamental frequency during reading; maximum intensity levels; sound pressure
      levels for soft, moderate, and loud productions of sustained /a/; and
      perturbation including jitter, shimmer, harmonics-to-noise ratio, and an s/z
      ratio. Pre- and post-performance samples of the "Rainbow passage" and sustained
      vowel phonation were rated by a group of blinded listeners that included
      professional voice trainers and speech pathologists. In addition, sample lines
      from the performance were played for the listeners to judge whether this
      technique would result in symptoms of vocal abuse. Eleven out of 12 professional
      voice trainers rated that this technique would result in symptoms of vocal abuse.
      The data revealed post-performance improvement in phonational range, maximum
      intensity levels, perturbation measures, and s/z ratio. Measures of maximum
      sustained phonation, fundamental frequency, and sound pressure levels remained
      stable. Videoendoscopy revealed normal function of the larynx and vocal folds.

PMID- 15567051
TI  - The association between upper trapezius activity and thorax movement in classical
      singing.
AB  - This study aimed to examine in classical singing the phasing of the activity in
      upper trapezius (TR) to upper and lower thorax movement and to the phasing of
      activity in the intercostals (INT) and in the lateral abdominal (OBL) muscles.
      Electromyographic (EMG) activity was recorded from the TR, INT, and OBL muscles
      on the right side. Thorax movement (TX) was traced with two strain gauge sensors
      placed around the upper and lower thorax. Four professional opera singers
      (soprano, mezzo, tenor, and baritone) and four advanced student classical singers
      (three sopranos and one mezzo) participated. Three of the professional singers
      were 33 years, and one was 40 years. The students were between 23 and 30 years.
      Different arias, freely chosen by the singers from their professional repertoire,
      served as the singing task for the opera singers. All students sang "Summertime"
      from Porgy and Bess. All subjects performed their task three times with variation
      in vocal loudness (normal, forte, piano). Thereafter, for all subjects, a
      biofeedback (BF) procedure was performed on TR to lower TR activity and a repeat
      performance of the singing tasks was carried out. EMG activity from the three
      recording sites and upper and lower TX circumference were compared before and
      after BF. A phasing of upper TR activity to INT and OBL activity was discovered,
      all muscles supporting the expiration phase. During phonation, the upper TR
      contributes in the compression of upper TX, thus serving as an accessory muscle
      of expiration. Group results from both opera singers and student singers showed
      that EMG activity was significantly lowered after BF. The lowered TR activity
      resulted in an expanded upper TX circumference and less TX respiratory movement
      after BF.

PMID- 15567052
TI  - Preparing the singing voice specialist revisited.
AB  - In review of singing voice specialist preparation, discussion can be chronicled
      prior to the establishment of Arts Medicine in 1987. Although discussion began in
      1984 (and earlier), no formal academic program currently exists to train the
      singing voice specialist. The need now is greater than ever for a formal program
      of study to prepare a person who seeks to be a singing voice specialist. The
      question of adequate preparation continues to be in need of an appropriate answer
      because no formal training programs or fellowships are available. It is essential
      to first define the role of singing voice specialists and the populations that
      they will encounter. To meet the needs of a diverse population, care of the
      professional voice demands cross-disciplinary training. Knowledge from the fields
      of music, science, medicine and communication disorders and
      experience/observation, clinical preparation, and research would provide for
      optimal preparation. To meet this need, development of a Masters degree program
      seems highly desirable. The structure of such a program is proposed, along with
      specific requirements outlined from the music and singing voice pathology
      components for a Masters Degree in Arts Medicine with a concentration in voice.

PMID- 15567053
TI  - Evaluating the effectiveness and efficiency of voice therapy using transnasal
      flexible laryngoscopy: a randomized controlled trial.
AB  - Transnasal flexible laryngoscopy (TFL) is an examination of laryngeal anatomy and
      physiology using continuous light. TFL is being used increasingly by voice
      pathologists in treatment but with little scientific evidence to support it. The
      purpose of this study was to evaluate the effectiveness and efficiency of TFL as
      a therapeutic tool. The study used a prospective randomized controlled trial.
      Fifty dysphonic subjects were recruited and randomly assigned to either a
      traditional treatment group or a TFL-assisted treatment group. The effectiveness
      of voice therapy in both treatment groups was measured with a package of voice
      outcome measures. Subjects in both treatment groups demonstrated statistically
      significant improvements after voice therapy (perceptual auditory rating of voice
      quality measurement p < 0.01; instrumental electroglottographic measurement p <
      0.01; patient questionnaire measurement p < 0.01). The time taken to complete
      treatment in both groups was recorded. The average (median) time taken to
      complete voice therapy in the TFL-assisted treatment group was 2 hours less than
      in the traditional treatment group (p < 0.01). Voice therapy with TFL as a
      therapy tool was effective and more efficient than traditional voice therapy.

PMID- 15567054
TI  - G. Paul Moore lecture: lessons in phonosurgery.

PMID- 15567055
TI  - Voice quality after carbon dioxide laser and conventional surgery for T1A glottic
      carcinoma.
AB  - The different types of small vocal fold tumor therapy allow the preservation of
      respiration and deglutition; the quality of phonation is the most important
      criterion for the patient. The aim of the study is to compare vocal function
      after treatment of T1a tumors by conventional and laser cordectomy. Fifty-seven
      male patients were included in the study: 27 underwent conventional cordectomy
      using an external approach, and 30 underwent an endoscopic microscopic laser
      cordectomy. Videolaryngoscopy was performed for each subject, and the maximal
      phonation time was measured. Spectrograms were recorded, and a perturbation
      analysis was performed if a clear harmonic structure was visible. Voices were
      perceptually rated by two experienced phoniatricians using the GRBAS scale. Even
      though a slightly better voice was found after conventional surgery throughout
      the data, no statistically significant difference was measured in the two groups.
      The data on voice outcome per se do not indicate the selection of one surgical
      approach over another.

PMID- 15567056
TI  - Efficacy of cidofovir injection for the treatment of recurrent respiratory
      papillomatosis.
AB  - To evaluate the efficacy of intralesional cidofovir injection for the treatment
      of recurrent respiratory papillomatosis (RRP). It is a prospective, open-label
      study design. This prospective study included 16 RRP patients, ages 9 to 68
      years, who were treated with intralesional injections of cidofovir combined with
      surgical excision of RRP. The disease states of the patients pretreatment and
      posttreatment were assessed by assigning RRP severity scores, examining the need
      for any surgical excision of RRP, and evaluating the presence of RRP upon long
      term follow-up. Sixteen patients were treated with cidofovir; however, three were
      lost to follow-up. Thirteen patients are the subjects of this report. This study
      group included three pediatric patients. Ten of thirteen patients (76.9%)
      responded to the treatment and are presently in remission. One patient did not
      respond, and two patients relapsed after initial success or had a partial
      response. The responders consisted of eight adults and two children. The mean
      number of injections the responders received was 3.5, and the average follow-up
      period of the responders was 25.4 months. No immediate complication of cidofovir
      treatment was evident. However, three patients were found to have significant
      vocal fold scarring after long-term follow-up. Cidofovir has been found to be
      efficacious in treating RRP. Further study regarding long-term follow-up and the
      assessment of possible side effects after cidofovir intralesional injection for
      RRP is required.

PMID- 15567057
TI  - Velopharyngeal aerodynamics of /m/ and /p/ in tracheoesophageal speech.
AB  - The purpose of this study was to compare oral pressure (P(o)), nasal airflow
      (V(n)), and velopharyngeal (VP) orifice area estimates from 12 tracheoesophageal
      (TE) and 12 laryngeal speakers as they produced /p/ and /m/ in syllable series.
      The findings were as follows: (1) TE speakers produced greater P(o) than the
      laryngeal speakers; (2) for /p/, TE speakers generated V(n), and VP orifice area
      estimates comparable with, or less than, the laryngeal speakers; and (3) for /m/,
      TE speakers had V(n) and VP orifice area estimates greater than the laryngeal
      speakers. The elevated P(o) could be the result of several factors such as high
      source driving pressures and vocal tract volume changes postlaryngectomy.
      Attempts at more precise articulation, and subsequently less coarticulation, by
      the TE speakers may explain the V(n) and VP orifice area estimates for /p/ and
      /m/. TE speakers may be limiting the oral-nasal cavity coupling for /p/ (smaller
      VP gap, less V(n)) in an attempt to produce a very precise oral /p/. For /m/, TE
      speakers may be attempting to overtly mark the consonant as a nasal (greater
      V(n), larger VP gap). Further studies are needed to confirm/refute the
      explanations postulated here regarding the VP aerodynamic differences that were
      identified.

PMID- 15567058
TI  - Aerodynamic characteristics of laryngectomees breathing quietly and speaking with
      the electrolarynx.
AB  - The primary purpose of this study was to investigate the aerodynamic
      characteristics of laryngectomees under two conditions: breathing quietly and
      speaking with electrolarynx. Twenty male adult subjects, 8 normal speakers, and
      12 laryngectomees participated the experiment. Airflow, pressure, and speech data
      were obtained simultaneously. The acceptability of electrolarynx speech under
      different conditions was also evaluated by 20 listeners (14 men, 6 women).
      Results indicated a higher peak expiration airflow and pressure among the
      laryngectomees as compared with the normal during breathing. Three different
      breathing patterns appeared among the laryngectomees when speaking with the
      electrolarynx: holding breath, exhaling, and breathing. Four long-time
      electrolarynx users held breath during speaking. Seven of 12 laryngectomees kept
      exhaling, whereas only 1 could breathe during speech production. In addition, (1)
      the acceptability of electrolarynx speech was the highest when speaking
      breathlessly; (2) no significant difference was found in the acceptability
      between the patterns of exhaling and breathing smoothly; and (3) the
      acceptability decreased if breathing quickly during phonation with the
      electrolarynx. It also suggests that the laryngectomees who can breathe during
      speaking may be more appropriate to use the new electrolarynx controlling the
      pitch by expiration pressure.

PMID- 15567059
TI  - cAMP-PKA signaling to the mitochondria: protein scaffolds, mRNA and phosphatases.
AB  - Energy metabolism and, specifically, the coupling of mitochondria to growth and
      survival is controlled by the cAMP-PKA pathway in yeast. In higher eukaryotes,
      cAMP signaling originating at the plasma membrane is distributed to different
      subcellular districts by cAMP waves received by PKA bound to PKA anchor proteins
      (AKAPs) tethered to these compartments. This review focuses on the subgroup of
      AKAPs that anchor PKA to the mitochondrial outer membrane (mtAKAPs). Only PKA
      anchored to mtAKAPs can efficiently transmit cAMP signals to mitochondria. mtAKAP
      complexes are remarkably heterogeneous. In addition to PKA regulatory subunits,
      they may include mRNAs, tyrosine phosphatase(s) and tyrosine kinase(s). Selective
      regulation of these components by cAMP-PKA integrates various signal transduction
      pathways and can determine which subcellular compartment receives the signal.
      Unveiling the interactions among the components of these large complexes will
      shed light on how cAMP and PKA regulate vital mitochondrial processes.

PMID- 15567060
TI  - The role of sphingosine-1-phosphate in smooth muscle contraction.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that is
      known to mediate diverse cellular responses including cell growth, survival, and
      migration. Most of these effects have been attributed to its binding to a
      specific subfamily of G protein-coupled receptors (GPCR), namely S1P(1-5). Recent
      studies have suggested that S1P also plays a prominent role in the contraction of
      various types of smooth muscle. This review provides a brief overview of its role
      in this process and also highlights how S1P-dependent signaling serves as an
      important regulator of smooth muscle contraction.

PMID- 15567061
TI  - Phorbol 12-myristate 13-acetate upregulates cyclooxygenase-2 expression in human
      pulmonary epithelial cells via Ras, Raf-1, ERK, and NF-kappaB, but not p38 MAPK,
      pathways.
AB  - In this study, we investigated the signaling pathway involved in cyclooxygenase-2
      (COX-2) expression and prostaglandin E2 (PGE2) release by phorbol 12-myristate 13
      acetate (PMA), a protein kinase C (PKC) activator, in human pulmonary epithelial
      cells (A549). PMA-induced COX-2 expression was attenuated by PKC inhibitors (Go
      6976 and Ro 31-8220), a Ras inhibitor (manumycin A), a Raf-1 inhibitor (GW 5074),
      a MEK inhibitor (PD 098059), and an NF-kappaB inhibitor (PDTC), but not by a
      tyrosine kinase inhibitor (genistein) or a p38 MAPK inhibitor (SB 203580). PMA
      also caused the activation of Ras, Raf-1, and ERK1/2. PMA-induced activation of
      Ras and Raf-1 was inhibited by Ro 31-8220 and manumycin A. PMA-mediated
      activation of ERK1/2 was inhibited by Ro 31-8220, manumycin A, GW 5074, and PD
      098059. Stimulation of cells with PMA caused IkappaBalpha phosphorylation,
      IkappaBalpha degradation, and the formation of a NF-kappaB-specific DNA-protein
      complex. The PMA-mediated increase in kappaB-luciferase activity was inhibited by
      Ro 31-8220, manumycin A, GW5074, PD 098059, and PDTC. Taken together, these
      results indicate that PMA might activate PKC to elicit activation of the Ras/Raf
      1/ERK1/2 pathway, which in turn initiates NF-kappaB activation, and finally
      induces COX-2 expression and PGE2 release in A549 cells.

PMID- 15567062
TI  - Stretch-induced Raf-1 activation in mesangial cells requires actin cytoskeletal
      integrity.
AB  - Glomerular capillary hypertension is a determinant of glomerulosclerosis and is
      modelled in vitro by exposure of mesangial cells to cyclic mechanical strain. In
      response to strain, Erk is activated and mediates extracellular matrix
      accumulation and mesangial cell proliferation. Erk activation is dependent on an
      intact cytoskeleton. Since Raf-1 lies upstream of Erk in response to numerous
      stimuli, and since its activation is dependent on membrane recruitment, we
      postulated that the cytoskeleton was essential for Raf-1 membrane recruitment and
      Erk activation. Primary rat mesangial cells (passages 8-20) were stretched at 1
      Hz and 27 kPa. Raf-1 was both phosphorylated on serine-338 (S338) and activated
      within 2 min of strain. The Raf-1 inhibitor, GW5074, dose-dependently blocked
      strain-induced Erk activation and Raf-1 phosphorylation. Although
      phosphatidylinositol-3-kinase (PI3-K) may mediate Raf-1 activation, PI3-K
      inhibition with wortmannin or LY294002 had no effect on stretch-induced Raf-1
      activation. Cytoskeletal disruption with cytochalasin D and the Rho-kinase
      inhibitor, Y-27632, however, blocked both Raf-1 phosphorylation and activation.
      Furthermore, membrane localization of Raf-1 was increased by strain and prevented
      by cytoskeletal disruption. Thus, strain leads to rapid membrane localization,
      S338 phosphorylation, and activation of Raf-1. These events are independent of
      PI3-K, but require Rho-kinase activation and an intact actin cytoskeleton.

PMID- 15567063
TI  - Inhibition by Rho-kinase and protein kinase C of myosin phosphatase is involved
      in thrombin-induced shape change of megakaryocytic leukemia cell line UT-7/TPO.
AB  - Thrombin induced a shape change of UT-7/TPO, a thrombopoietin-dependent human
      megakaryocytic cell line. Expression of myosin light chain (MLC) kinase was
      negligible in UT-7/TPO cells, while Rho-kinase and protein kinase C (PKC) were
      detected. Thrombin stimulated both monophosphorylation at Ser19 and
      diphosphorylation at Thr18 and Ser19 of 20 kDa MLC, as well as phosphorylation of
      myosin-binding subunit (MBS) and PKC-potentiated inhibitory phosphoprotein of
      myosin phosphatase (CPI). The Rho-kinase inhibitor Y-27632 [(+)-(R)-trans-(1
      aminoethyl)-N-(4-phynidyl) cyclohexane-carboxamide dihydrochloride, monohydrade]
      strongly inhibited thrombin-induced shape change, MBS phosphorylation, and mono-
      and diphosphorylation of MLC. The PKC inhibitor GF109203X (2-[1-(3
      dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide) partially
      inhibited thrombin-induced shape change and MLC diphosphorylation even at the
      concentration that completely inhibited thrombin-induced CPI phosphorylation. In
      shape-changed UT-7/TPO cells induced by thrombin, phosphorylated MBS and CPI were
      colocalized with diphosphorylated MLC at pseudopods, whereas monophosphorylated
      MLC was mainly located in the cortical region. The accumulation of
      diphosphorylated MLC was blocked by preincubation with either Y-27632 or
      GF109203X. These results suggest that Rho-kinase is responsible for the induction
      of MLC phosphorylation in thrombin-induced shape change of UT-7/TPO cells and
      that myosin phosphatase inactivation through Rho-kinase-MBS and PKC-CPI pathways
      could be necessary for enhancement of MLC diphosphorylation which promote the
      pseudopod formation.

PMID- 15567064
TI  - The effect of Sildenafil on human platelet secretory function is controlled by a
      complex interplay between phosphodiesterases 2, 3 and 5.
AB  - Human platelets contain the cyclic nucleotide-hydrolyzing phosphodiesterases
      (PDEs) 2, 3 and 5. The cGMP-PDE5 inhibitors Sildenafil and Zaprinast have been
      demonstrated to potentiate the anti-platelet aggregatory effect of NO donors like
      sodium nitroprusside (SNP) in vitro but the mechanisms of Sildenafil's action on
      the secretory function of human platelets have not been analysed in detail. In
      the present paper, we show (1) that both compounds potentiate the SNP-induced
      increase in cGMP in human platelets concentration-dependently. (2) However,
      whereas Sildenafil plus SNP treatment only partially inhibits thrombin-induced
      release of serotonin, the less selective Zaprinast plus SNP cause a complete
      inhibition. (3) The inhibition mediated by Sildenafil plus SNP is limited to low
      compound concentrations at which cAMP levels are increased, probably due to cGMP
      mediated inhibition of PDE3. (4) High concentrations of Sildenafil (plus SNP)
      neither affect cAMP levels, likely due to the activation of PDE2, nor inhibits
      the release of serotonin. Thus, increases in both cyclic nucleotides seem to
      control platelet function. (5) Accordingly, treatment with increasing
      concentrations of Sildenafil plus SNP and a selective PDE2 inhibitor, which by
      its own has no effect, induced a concentration-dependent increase in cAMP and
      complete inhibition of platelet activation. In summary, our data indicate that
      Sildenafil inhibits secretory function of human platelets at least in part due to
      the cGMP-mediated effects on intracellular cAMP and that entire inhibition of
      serotonin release from thrombin-activated platelets is controlled by both cyclic
      nucleotides.

PMID- 15567065
TI  - Fer kinase sustains the activation level of ERK1/2 and increases the production
      of VEGF in hypoxic cells.
AB  - Fer is a nuclear and cytoplasmic tyrosine kinase that is ubiquitously expressed
      in mammalian cells. Herein we show that Fer sustains a key signaling step in
      hypoxic cells. Knock-down of the Fer protein using a specific siRNA decreased the
      production of VEGF by the hypoxic cells. Conversely, ectopic expression of this
      kinase led to an elevated production of VEGF under hypoxia. At the molecular
      level, Fer was found to associate with ERK1/2 and this interaction was
      intensified under hypoxia. Moreover, Fer increased the activation levels of
      ERK1/2, and reducing the level of Fer, impaired the activation of ERK1/2 in
      hypoxic cells. Blocking the MEK-ERK1/2 signaling pathway with the MEK inhibitors
      U0126, or PD98059 led to the abrogation of ERK1/2 activity in hypoxic cells, an
      effect that was counteracted by Fer. Hence, Fer sustains the activation of ERK1/2
      and increases the production of VEGF in hypoxic cells, without affecting the MEK
      ERK signaling pathway.

PMID- 15567066
TI  - CCL3 (MIP-1alpha) induces in vitro migration of GM-CSF-primed human neutrophils
      via CCR5-dependent activation of ERK 1/2.
AB  - CCL3 (MIP-1alpha), a prototype of CC chemokines, is a potent chemoattractant
      toward human neutrophils pre-treated with GM-CSF for 15 min. GM-CSF-treated
      neutrophils migrate also to the selective CCR5 agonist CCL4 (MIP-1beta). CCL3-
      and CCL4-triggered migration of GM-CSF-primed neutrophils was inhibited by the
      CCR5 antagonist TAK-779. Accordingly, freshly isolated neutrophils express CCR5.
      Extracellular signal-regulated kinases (ERK)-1/2 and p38 mitogen-activated
      protein kinase (MAPK) inhibitors blocked CCL3-induced migration of GM-CSF-primed
      neutrophils. When the activation of ERK-1/2 and p38 MAPK by CCL3 and the
      classical neutrophilic chemokine CXCL8 (IL-8) were compared, both the chemokines
      were capable of activating p38 MAPK. On the contrary, whereas both ERK-1 and ERK
      2 were activated by CXCL8, no ERK-1 band was detectable after CCL3 triggering.
      Finally, neutrophil pre-treatment with GM-CSF activated both ERK-1 and ERK-2.
      This suggests that by activating ERK-1, GM-CSF renders neutrophils rapidly
      responsive to CCL3 stimulation throughout CCR5 which is constitutively expressed
      on the cell surface.

PMID- 15567067
TI  - Regulation of GDF-8 signaling by the p38 MAPK.
AB  - Growth differentiation factor-8 (GDF-8), a member of the TGF-beta superfamily, is
      a negative regulator of skeletal muscle growth, which functions through
      activation of the Smad proteins. We found that GDF-8 can activate the p38 mitogen
      activated protein kinase (MAPK) through the TGF-beta-activated kinase 1 (TAK1),
      and this appeared to be independent of Smad signaling. GDF-8-induced
      transcriptional activation was inhibited by expression of dominant negative MKK6
      or treatment with the p38 inhibitor SB203580, while overexpression of wild-type
      forms of either MKK6 or p38 augmented GDF-8-induced transcriptional activity. In
      addition, ATF-2, a known transcription factor target of p38, was found to be
      phosphorylated on GDF-8 stimulation and was detected in a complex with
      Smad3/Smad4 upon GDF-8 treatment. Furthermore, we found that the p38 MAPK played
      an important role in GDF-8-induced inhibition of proliferation and upregulation
      of the cyclin kinase inhibitor p21. Together, these results highlight a
      functional link between the p38 MAPK and GDF-8-activated Smad pathways, and
      identify a critical role for the p38 MAPK in GDF-8's function as a negative
      regulator of muscle growth.

PMID- 15567068
TI  - Role of protein kinase Cdelta in UV-B-induced apoptosis of macrophages in vitro.
AB  - We have previously reported that murine peritoneal macrophages exposed to
      ultraviolet B (UV-B; 100 mJ/cm2) undergo apoptosis, as indicated by alterations
      in cell morphology, caspase-3 activation, poly (ADP-ribose) polymerase (PARP)
      cleavage, DNA fragmentation, sustained activation of p38/c-Jun N-terminal kinase
      (JNK) mitogen-activated protein kinases (MAPKs) and inactivation of p42/44 MAPKs.
      It is now reported that macrophages undergoing UV-B-induced apoptosis show
      enhanced expression of protein kinase Cdelta (PKCdelta) in a time-dependent
      manner. Pretreatment of macrophages with PKCdelta-specific inhibitor rottlerin
      prior to the UV-B irradiation inhibits activation of caspase-3, PARP cleavage,
      DNA fragmentation and release of intracellular Ca2+. Inhibition of PKCdelta also
      blocks the sustained activation of p38 and JNK MAPKs as well as inactivation of
      p42/44 MAPKs. PKCalpha and PKCbeta1 expression also increases during UV-B-induced
      apoptosis in macrophages. Inhibition of these two isoforms with Go6976 slightly
      suppresses caspase-3 activation, PARP cleavage, DNA fragmentation and release of
      intracellular Ca2+, but has no effect on the sustained activation of p38/JNK
      MAPKs or inactivation of p42/44 MAPKs. It is, therefore, suggested that
      activation of PKCdelta might play an important role in the UV-B-induced apoptosis
      and that specific activated isoforms of PKC may have distinct functions in cell
      death.

PMID- 15567069
TI  - Involvement of PKCalpha/beta in TLR4 and TLR2 dependent activation of NF-kappaB.
AB  - Protein kinase C (PKC)alpha/beta dependent signaling events downstream of TLR4 or
      TLR2 were investigated in neutrophils stimulated with LPS or PGN. Pretreatment of
      neutrophils with the structurally distinct PKCalpha/beta inhibitors Go6976 or
      GF109203X decreased nuclear translocation of NF-kappaB and production of the
      proinflammatory cytokine TNF-alpha. Inhibition of PKCalpha/beta also prevented
      LPS or PGN induced phosphorylation of IKKalpha/beta, phosphorylation and
      degradation of IkappaB-alpha, as well as phosphorylation of the p65 subunit of NF
      kappaB. Activation of p38, JNK, and ERK 1/2 in response to TLR2 engagement was
      diminished in neutrophils in which PKCalpha/beta was inhibited. However, no
      alteration in the activation of these kinases was found in TLR4 stimulated
      neutrophils when PKCalpha/beta was blocked. Such results indicate that distinct
      intracellular signalling pathways leading to MAPK activation are induced by TLR4
      and TLR2 stimulation. PKCalpha/beta can regulate NF-kappaB dependent
      transcription in neutrophils both by enhancing nuclear translocation of NF-kappaB
      and also by stimulating phosphorylation of the p65 subunit.

PMID- 15567070
TI  - Roles of the intracellular regions of angiotensin II receptor AT2 in mediating
      reduction of intracellular cGMP levels.
AB  - We have shown previously that the angiotensin II (Ang II) receptor AT2 reduces
      the intracellular levels of cGMP in Xenopus oocytes when activated by ligand
      binding, and the C-terminal cytoplasmic tail of the AT2 acts as a negative
      regulator of this function. Here we report the effects of mutations in the 2nd
      and 3rd intracellular loops of AT2 on AT2-mediated cGMP reduction. Mutating the
      highly conserved DRY motif (D141G-R142G-Y143A) of the 2nd ICL implicated in
      activating G(alpha) subunit of trimeric G-proteins did not affect AT2-mediated
      cGMP reduction. Moreover, anti-Gialpha antibody or phosphodiesterase inhibitor
      IBMX did not inhibit AT2-mediated cGMP reduction, suggesting that Gialpha
      activation and subsequent phosphodiesterase activation are not involved in this
      function. In contrast, mutations T250R-R251N and L255F-K256R located in the C
      terminus of the 3rd ICL of AT2 retained ligand-binding properties of the wild
      type AT2, and its ability to interact with the ErbB3 in yeast two-hybrid assay,
      but abolished AT2-mediated cGMP reduction. Similarities in the roles of ICLs of
      AT2 in AT2-mediated cGMP reduction in oocytes, and AT2-mediated SHP1 activation
      in COS-7 cells, (need of 3rd ICL for both functions and lack of involvement of
      DRY motif), suggest that the cascade of events in these two signaling mechanisms
      could be similar, and that an oocyte-specific SHP1-like protein may be involved
      in AT2-mediated cGMP reduction in these cells.

PMID- 15567071
TI  - Language disorder in schizophrenia as a developmental learning disorder.
AB  - Receptive language disorder in schizophrenia is hypothesized to represent a
      learning disorder that involves a neurodevelopmental etiology. It is argued that
      a preexisting developmental language disorder may characterize a subset of
      schizophrenia patients. A primary deficit in the temporal dynamics of brain
      function is assumed to cause receptive language disorder in schizophrenia. This
      hypothesized core deficit includes both disturbance in the processing of rapid,
      sequential information and disruptions to patterns of brain activation and
      synchronization. These timing deficits may alter the way associative connections
      are formed and/or accessed in semantic memory. It is suggested that abnormalities
      in second-messenger pathways of subcortical-cortical circuitry offer an
      etiological nexus for language dysfunction in schizophrenia and developmental
      dyslexia.

PMID- 15567072
TI  - A case-control study of the relationship between the metabotropic glutamate
      receptor 3 gene and schizophrenia in the Chinese population.
AB  - Recent studies of the association between the metabotropic glutamate receptor 3
      gene (GRM3) and schizophrenia have produced conflicting results, although GRM3 is
      a promising candidate gene. Fujii et al. found a single nuclear polymorphism
      (SNP) for within this gene, rs1468412 to have a positive association to
      schizophrenia in Japanese patients. To investigate this further, we genotyped 7
      SNPs around GRM3 including rs1468412, in 752 Chinese patients with schizophrenia
      and 752 controls using Taqman technology. We did not detect any association
      between rs1468412 and schizophrenia, however we found differences in the allele
      frequency distribution of SNP rs2299225 (p=0.0297, odds ration [OR]=1.44, 95%
      confidence interval 1.05-1.99) between cases and controls. Moreover, the overall
      frequency of haplotypes constructed from three SNPs including rs2299225 showed
      significant differences between cases and controls (p=0.0017). Our results
      partially support the previous studies in other ethnic groups and indicate that
      the GRM3 gene may play an important role in the etiology of schizophrenia in the
      Han Chinese.

PMID- 15567073
TI  - COMT Val(158)Met and BDNF C(270)T polymorphisms in schizophrenia: a case-control
      study.
AB  - In a multicenter study involving 217 subjects of European ancestry [106 patients
      with schizophrenia and 111 healthy subjects], we tested the hypothesis that the
      catechol-O-methyl transferase (COMT) Val(158)Met and/or the brain-derived
      neurotrophic factor (BDNF) C(270)T gene polymorphisms are associated with
      schizophrenia. The COMT and BDNF genotype and their allele distribution did not
      differ between patients with schizophrenia and healthy comparison subjects. These
      results do not support the hypothesis that the COMT Val(158)Met or BDNF C(270)T
      gene polymorphisms are associated with liability to schizophrenia.

PMID- 15567074
TI  - The C/C genotype of the C957T polymorphism of the dopamine D2 receptor is
      associated with schizophrenia.
AB  - The T allele of the human dopamine D2 receptor (DRD2) gene C957T polymorphism is
      associated with reduced mRNA translation and stability. This results in decreased
      dopamine induced DRD2 upregulation and decreased in vivo D2 dopamine binding.
      Conversely, the C allele of the C957T polymorphism is not associated with such
      changes in mRNA leading to increased DRD2 expression. PET and postmortem binding
      studies show that schizophrenia is often associated with increased DRD2
      availability. We report that on the basis of comparing the frequencies of the C/C
      and T/T genotypes of 153 patients with schizophrenia and 148 controls that
      schizophrenia is associated with the C/C genotype. The C957T shows a population
      attributable risk for schizophrenia of 24% and an attributable risk in those with
      schizophrenia of 42%. Increased expression of D2 receptors associated with the C
      allele is likely to be important in the underlying pathophysiology of at least
      some forms of schizophrenia. Enhanced understanding of schizophrenia afforded by
      this finding may lead to advances in treatment and prevention.

PMID- 15567075
TI  - Explaining variation in the premorbid adjustment of schizophrenia patients: the
      role of season of birth and family history.
AB  - Several studies have shown that patients with schizophrenia are more likely to be
      born in the winter and early spring than at any other time of the year.
      Furthermore, some studies have reported that winter-born patients differ from non
      winter-born patients in terms of risk factors, symptoms, sensory abnormalities
      and brain morphology. Associations between season of birth and premorbid
      adjustment (PMA), however, are still unclear. OBJECTIVE: The main purpose of this
      study was to determine whether winter-born and non-winter-born schizophrenia
      patients differ in terms of PMA and to examine how family history of
      schizophrenia-spectrum disorders may influence the association. METHOD: Data on
      four PMA dimensions (attention, internalizing, externalizing and social problems)
      and family history were gathered from 37 schizophrenia patients (26 males and 11
      females) and their mothers. RESULTS: Non-winter-birth and a positive family
      history of schizophrenia-spectrum disorders were associated with worse PMA.
      Results suggest that, although no significant interaction was found, season of
      birth and family history appear to work together in explaining distinct
      dimensions of PMA.

PMID- 15567076
TI  - Association between dopamine D3 receptor gene polymorphisms and schizophrenia in
      an isolate population.
AB  - There are several lines of evidence implicating the dopamine D3 receptor in the
      pathophysiology of schizophrenia. The Ser9Gly polymorphism of the dopamine D3
      receptor gene (DRD3) has been the most extensively investigated DRD3 variant in
      connection with the disease but results have been inconclusive. Recent reports
      indicate that the Ser9Gly polymorphism is in linkage disequilibrium with other
      markers, but association studies between DRD3 haplotypes and schizophrenia have
      had mixed results. Genetic heterogeneity may be one of the causes of
      contradicting results. In order to clarify the role of DRD3 alterations in the
      aetiology of disease, we have investigated three D3 genetic variants (Ser9Gly, 
      205-G/A, -7685-G/C) in a sample of patients with schizophrenia or schizoaffective
      disorder (N=118) and controls (N=162) recruited from a human isolate from Navarra
      (Northern Spain) of Basque origin. Although no association was found between the
      Ser9Gly or the -205-A/G polymorphisms and disease, an excess of allele -7685-C
      was observed in patients (p=0.002 after correction for multiple analyses).
      Haplotype analysis shows the three markers to be in strong linkage disequilibrium
      (p<0.0001) and strongly associated with disease (p<1x 10(-5)). These results may
      suggest that these polymorphisms exert a combined or synergistic effect on
      susceptibility to schizophrenia, or are in linkage with an unknown causative
      factor. However, further replication in independent samples is required.

PMID- 15567077
TI  - Meta-analysis shows schizophrenia is not associated with the 40-base-pair repeat
      polymorphism of the dopamine transporter gene.
AB  - OBJECTIVE: Several case-control studies examined an association between
      schizophrenia and the 40-bp variable number tandem repeat (VTNR) polymorphism in
      the 3'-UTR of the dopamine transporter gene (SLC6A3). The results of these
      studies have been equivocal due to small sample size and low power. This meta
      analysis has the aim to evaluate the collective evidence for an association
      between the VTNR polymorphism and schizophrenia. METHOD: Different meta-analyses
      were performed, sequentially considering the 9- and 10-repeat alleles and
      different genotypes (genotypes 9/9, 9/10, 10/10) as risk factors for
      schizophrenia. Analyses of the alleles included 659 cases and 563 controls from
      six case-control studies. RESULTS: The pooled OR from each analysis approximated
      1.0, and none were significant. Lack of significance attributable to the negative
      effects of single large studies or to heterogeneity between the studies was
      excluded. CONCLUSION: Despite over 90% power to detect a significant odds ratio
      as small as 1.3, no association was observed. Considering the cumulative evidence
      from six case-control studies and results from additional family-based studies,
      it seems unlikely that the 40-base-pair VTNR polymorphism of the SLC6A3 gene
      influences risk for schizophrenia.

PMID- 15567078
TI  - Smaller corpus callosum subregions containing motor fibers in schizophrenia.
AB  - Neuropsychological and neurophysiological studies provide evidence for abnormal
      interhemispheric communication in schizophrenia. These abnormalities may have a
      substrate in structural irregularities of the corpus callosum. This study
      investigated schizophrenia patients (n=27) and healthy comparison subjects
      (n=31). Global and regional measurements of the corpus callosum were acquired
      from one midsagittal SPGR slice. Eight subregions were approximately matched to
      fiber pathways from cortical regions. Overall effects of diagnosis [Wilks' Lambda
      F(8,46)=2.45, p=0.03] and diagnosis by age interaction [Wilks' Lambda
      F(8,46)=2.58, p=0.02] were found in a MANCOVA of the eight functionally specific
      subregions. Specifically, chronic schizophrenia was associated with a smaller
      rostral body [lower by 6.9%, F(1,53)=9.70, p=0.003] and anterior midbody [lower
      by 9.7%, F(1,53)=4.89, p=0.03] subregions. The rostral body and anterior midbody
      subregions of the corpus callosum primarily have premotor, supplementary motor,
      and motor cortical fibers transversing through them. Functional abnormalities of
      the associated cortical regions are reported in schizophrenia. These novel
      findings suggest that structural abnormalities of the corpus callosum exist in
      schizophrenia, with perhaps the motor-specific subregions affected more than
      others. Structural differences in the corpus callosum may be a substrate for
      interhemispheric functional dysconnectivity in schizophrenia.

PMID- 15567079
TI  - Evidence for altered neuronal organisation within the planum temporale in major
      psychiatric disorders.
AB  - Reductions in neuronal size and glial cell density have been described in the
      frontal cortex in major psychiatric disorders. In this investigation, we
      performed a cytoarchitectural assessment within the planum temporale (PT), an
      auditory association region located within the superior temporal gyrus, using two
      dimensional (2D) measures of cell size and density and spatial point pattern
      analysis. In sections of the PT from subjects with schizophrenia, bipolar
      disorder, major depressive disorder and controls (15 subjects per group), the
      laminar distribution and size of all neurons and glial cell nuclei was recorded.
      Spatial point pattern investigation demonstrated reduced neuronal clustering in
      bipolar disorder (p=0.033) and schizophrenia (p=0.027) compared with controls.
      Statistical analyses comparing each of the patient groups with the control group
      failed to identify differences in neuronal density between groups. Neuronal size
      was reduced in cortical layer 3 (p=0.02) and glial cell density reduced in
      cortical layer 6 (p=0.05) in bipolar disorder relative to controls but these
      findings did not remain significant after adjusting for six layer-wise
      comparisons. We propose that alterations in cortical cytoarchitecture within this
      region are subtle and involve reduced clustering of neurons, which may be due to
      altered neuronal organisation within cortical mini-columns or within cortical
      layers.

PMID- 15567080
TI  - A cross-study meta-analysis and three-dimensional comparison of cell counting in
      the anterior cingulate cortex of schizophrenic and bipolar brain.
AB  - Using a two-dimensional cell counting approach, a 1991 study in the anterior
      cingulate cortex (ACCx) detected a reduction in the density of nonpyramidal
      neurons in layers II-VI of schizophrenic subjects. Schizophrenics without
      superimposed mood disturbances showed a 16% decrease in layer II, while
      schizoaffectives showed a 30% decrease, suggesting that a decreased density of
      nonpyramidal neurons in layer II of ACCx might vary more strongly with affective
      disorder than with schizophrenia. Two follow-up studies from this laboratory, one
      a replication of that reported in 1991 and the other an analysis of tyrosine
      hydroxylase immunoreactive fibers, were undertaken in ACCx of normal controls and
      schizophrenics. These three data sets have been combined and a meta-analysis of
      the density of pyramidal, nonpyramidal and glial cells was performed to explore
      whether changes in the density of interneurons in ACCx may be a reliable finding
      in the major psychoses. Not all groups have reported this finding, but several
      had employed a different cell counting technique (i.e. three dimensional optical
      dissector), which could help to explain the discrepant findings in schizophrenia
      and affective disorder. The data from each of three different studies (now
      designated as studies A, B and C, respectively) have been internally normalized,
      combined into a single dataset and analyzed using nonparametric statistics.
      Tissue blocks from a subset of cases in study B (six controls, six schizophrenics
      and six bipolars) were embedded in celloidin and counted using an "unbiased"
      three dimensional counting method (study D). The data from studies A and B
      indicate that the density of nonpyramidal neurons in layer II of ACCx in the
      schizoaffective and bipolar samples was significantly decreased. In the
      schizophrenics, the nonpyramidal neurons were also decreased, but only by 15%.
      All three groups also showed a decrease of pyramidal neurons in layers IV, V and
      VI, but this difference was significant only in layer IV of the schizophrenics.
      When data from study C were added, the differences in pyramidal and nonpyramidal
      neurons were less striking. For study D, the pattern of findings are strikingly
      similar to those obtained in studies A, B and C, indicating that both 2D and 3D
      cell counting methodologies are capable of detecting the same differences. Taken
      together, these results indicate that the earlier finding of a decreased density
      of nonpyramidal neurons in ACCx of schizophrenics is consistent across non
      overlapping subjects and/or methods in four separate studies, and is more
      pronounced in schizoaffective and bipolar subjects than in schizophrenics without
      superimposed mood disturbance.

PMID- 15567081
TI  - Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric
      MRI study.
AB  - OBJECTIVE: The thalamus, as a composite of several functionally very different
      nuclei, is a major relay and filter station in the CNS and is significantly
      involved in information processing and gating. The aim of our study is to
      investigate first-episode and chronic patients and controls to shed light on the
      potential pathogenetic role of the thalamus in schizophrenia and to assess the
      relationship between thalamic volumes and psychopathology ratings. METHODS: Forty
      three male right-handed chronic and 25 male right-handed first-episode
      schizophrenic patients treated at the psychiatric hospital of the Ludwig
      Maximilians University in Munich and 50 male control subjects were enrolled into
      the study. Demographic information and current symptom profile of all
      schizophrenic subjects were assessed using a semistructured interview, including
      a variety of measures relevant to the study. Volumetry of the thalamic gray and
      white matter was obtained with 1.5 T MRI, using the BRAINS software application.
      RESULTS: No significant differences regarding thalamic volumes were detected
      across groups. However, negative symptoms were significantly correlated with
      thalamic volumes in first-episode patients, whereas duration of illness and
      extrapyramidal symptoms were related to thalamic volumes in chronic patients.
      SUMMARY: Our findings indicate that, while the thalamus might be involved in the
      pathogenesis of negative symptoms, thalamic volume reduction is not a required
      element in the pathophysiology of the schizophrenic phenotype.

PMID- 15567082
TI  - Anterior and posterior hippocampal volumes in schizophrenia.
AB  - BACKGROUND: While the evidence for hippocampal structural abnormalities in
      schizophrenia is now well accepted, whether there is differentially greater
      volume loss within specific subregions of the hippocampus remains a matter of
      some debate. Here we present volume estimates of anterior and posterior
      hippocampal volumes using a novel morphometric protocol. METHODS: We studied 25
      male patients with schizophrenia and 25 age-matched male control subjects.
      Hippocampal volumes were estimated using a three-dimensional morphometric
      protocol for the analysis of high-resolution structural magnetic resonance images
      (MRI). Anterior hippocampal volumes were differentiated from posterior
      hippocampal volumes by the presence of the uncus in coronal slices. RESULTS:
      While the patients with schizophrenia had significantly smaller overall
      hippocampal volumes relative to the control group, there was no evidence for a
      topographically specific pattern of volume loss along the anterior-posterior
      hippocampal axis. CONCLUSIONS: These results confirm the presence of overall
      hippocampal volume decreases in patients with schizophrenia, but do not confirm a
      topographically specific localization of this effect. It appears that the
      hippocampal volume deficit in schizophrenia is diffuse, a finding that has
      important consequences for understanding the underlying pathophysiologic
      mechanisms in schizophrenia.

PMID- 15567083
TI  - Insular volumes in first-episode schizophrenia: gender effect.
AB  - Insula is a multimodal sensory integration region that acts as a gateway between
      somatosensory areas and limbic structures such as amygdala. Only a handful of
      region of interest (ROI) studies have suggested insular volume reduction in
      patients with schizophrenia but none have documented a gender effect on the
      volume of this structure. The authors used magnetic resonance images to measure
      insular volumes in previously untreated patients with first-episode schizophrenia
      (N=30) relative to those of healthy comparison subjects (N=30). Correlations with
      symptom severity were carried out. Intracranial volume was used as a covariate in
      the analysis. Female patients (N=15) had significantly reduced right insular
      volume relative to healthy female comparison subjects (p<0.05). On preliminary
      analysis, the right and left insular volumes in female patients had significant
      negative correlations with the positive symptoms scores (p<0.05), but not on
      correcting for multiple comparisons. Insula is developmentally and
      phylogenetically a watershed region where the more primitive allocortex
      transitions into the more developed isocortex. Thus its role as a substrate of
      neurodevelopmental hypothesis in schizophrenia and the interplay with gender
      deserves more attention.

PMID- 15567084
TI  - Functional near infrared spectroscopy reveals differences in self-other
      processing as a function of schizotypal personality traits.

PMID- 15567085
TI  - The dopamine D4 receptor VNTR in Polish schizophrenia patients.

PMID- 15567086
TI  - Association of the 120-bp duplication in the dopamine D4 receptor gene and
      schizophrenia in a sample of Danish subjects.

PMID- 15567088
TI  - Prevalence of HCV coinfection in HIV-infected individuals in Nigeria and
      characterization of HCV genotypes.
AB  - BACKGROUND: Coinfection with hepatitis C virus (HCV) in individuals infected with
      HIV is associated with a higher incidence of liver injury, hepatic
      decompensation, and decreased survival time than that seen in an HIV-monoinfected
      population. While prevalence studies on HIV/HCV coinfection have been performed
      in the U.S. and in some European countries, little is known about coinfection
      rates in Africa. DESIGN: Retrospectively collected specimens from 146 confirmed
      HIV-positive individuals in Nigeria who had access to antiretroviral therapy
      (ART) were tested for HCV RNA, using the VERSANT HCV RNA qualitative assay (TMA),
      and, if HCV RNA-positive, for HCV genotype using the VERSANT HCV genotype assay
      (LiPA). RESULTS: Twelve out of the 146 individuals tested (8.2%) were HCV
      positive. Nine of the 12 HCV-positive individuals were infected with HCV genotype
      1 (five 1a, three 1b, one non-subtypable) and three were infected with HCV
      genotype 2 (all non-subtypable). Coinfected individuals were more likely to be
      male, older, and have lower CD4+ cell counts than HIV-monoinfected individuals,
      although none of the differences reached statistical significance. CONCLUSION:
      The results highlight the potential public health impact of HCV infection in
      Nigeria, where anti-HCV testing is generally not performed in HIV-infected
      populations or in most blood transfusion centers.

PMID- 15567089
TI  - Virologic therapy response significantly correlates with the number of active
      drugs as evaluated using a LiPA HIV-1 resistance scoring system.
AB  - BACKGROUND: Resistance testing is increasingly accepted as a tool in guiding the
      selection of human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy
      in HIV-1 infected individuals who fail their current regimen. OBJECTIVES: To
      descriptively compare the correlation between virologic treatment response and
      results using three genotypic HIV-1 drug resistance interpretation systems: the
      VERSANT HIV-1 Resistance Assay (LiPA) system and two sequence-based
      interpretation systems. STUDY DESIGN: Specimens from 213 HIV-1-infected subjects,
      either starting (n=104) or switching to (n=109) a regimen of three or four
      antiretroviral drugs, were collected retrospectively at baseline and after 3
      months of uninterrupted therapy. The correlation between viral load change and
      the number of predicted active drugs in the treatment regimen was assessed. An
      interpretation algorithm was recently developed to process VERSANT HIV-1
      Resistance Assay (LiPA) data. The number of active drugs predicted using this
      algorithm was rank correlated with the viral load change over a 3-month treatment
      period. For comparison, a similar calculation was made using two sequence-based
      algorithms (REGA version 5.5 and VGI GuideLines Rules 4.0), both applied on the
      same sequences. RESULTS: Statistically significant (p<0.05) correlation
      coefficients for each of the three HIV-1 drug resistance interpretation systems
      were observed in the treatment-experienced subjects on a 3-drug regimen (-0.39, 
      0.38, and -0.42, respectively) as well as on a 4-drug regimen (-0.33, -0.31, and 
      0.37, respectively). However, no significant correlation was observed in
      treatment-naive subjects, probably due to the very low frequency of drug
      resistance in these subjects. CONCLUSION: All three genotypic drug resistance
      interpretation systems (LiPA version 1, REGA version 5.5, and VGI GuideLines
      Rules 4.0) were statistically significantly correlated with virologic therapy
      response as measured by viral load testing.

PMID- 15567090
TI  - Antigenic complementarity among AIDS-associated infectious agents and molecular
      mimicry of lymphocyte proteins as inducers of lymphocytotoxic antibodies and
      circulating immune complexes.
AB  - BACKGROUND: People at risk for acquired immunodeficiency syndrome (AIDS) have
      high rates of cofactor infections in addition to HIV, including cytomegalovirus,
      hepatitis viruses, Mycobacteria, Mycoplasmas, and Staphylococcus aureus. Most
      people with AIDS also develop lymphocytotoxic antibodies (LCTA) and circulating
      immune complexes (CIC). While HIV proteins mimic HLA antigens, many cofactor
      agents mimic CD4 antigens. It has therefore been proposed that cofactor
      infections may interact with HIV by producing complementary antigens that induce
      LCTA and CIC, and that the resulting immunological dysfunction is part of AIDS
      pathogenesis. OBJECTIVES: To test (1) whether HIV and its cofactor infections
      elicit complementary (idiotype-anti-idiotype) antibodies, and (2) if any of these
      antibodies mimic anti-lymphocyte antibodies. STUDY DESIGN: Two immunological
      methods are employed to test for antibody complementarity: (1) double antibody
      diffusion, a modification of Ouchterlony immunodiffusion, in which antibodies are
      tested for their ability to precipitate each other; (2) double-antibody ELISA, in
      which an antibody against one infectious agent is adsorbed to an ELISA plate and
      an antibody against a second agent is used to detect the first. RESULTS: Data on
      over a thousand double antibody diffusion (DAD) and about 70 DA-ELISA experiments
      are reported. These show that only specific pairs of antibodies are
      complementary: HIV-CMV; HIV-HBV; HIV-tuberculosis; HIV-mycoplasmas; HIV-S.
      aureus; and CMV-mycoplasmas. In addition, HIV antibodies precipitate CD4
      antibodies; CMV antibodies precipitate HLA-DR antibodies; while mycobacteria and
      mycoplasma antibodies precipitate macrophage antibodies. CONCLUSIONS: Antibodies
      elicited by HIV infection can interact with antibodies elicited by cofactor
      infections to form CIC, and some of these antibodies mimic lymphocyte antibodies
      so that they may function as LCTA. Since LCTA and CIC are associated with
      increased lymphocyte death in AIDS, the immune response against cofactors in HIV
      may play a significant role in AIDS pathogenesis. The fact that both HIV and
      cofactors elicit antibodies with LCTA characteristics may pose problems for
      vaccine development.

PMID- 15567091
TI  - Exclusion of HIV epitopes shared with human proteins is prerequisite for
      designing safer AIDS vaccines.
AB  - BACKGROUND: The safety of a potential AIDS vaccine is an issue that will become
      critical at later stages of product development and needs to be addressed before
      it is too late. OBJECTIVE: In order to design safer vaccine, the HIV antigens, to
      be deployed in it, should be free of regions that are either present in human
      proteins or exhibit pronounced structural similarity to proteins responsible for
      important physiological functions. STUDY DESIGN: The approach is based on the use
      of an original matrix predicting the antigenic similarity of amino acids. This
      mathematical approach developed by us was applied for identification of fragments
      with similarity to human proteins within potentially immunodominant regions of
      HIV proteins. A potential self-sensitization by viral quasispecies with variants
      of hypervariable V3 region, generated as a result of immune pressure on the
      immunodominant region of envelope, was considered in detail. RESULTS: Viral
      fragments occurring in normal human proteins as well as regions exhibiting high
      similarity to proteins responsible for physiological homeostasis were identified
      in every HIV protein at a frequency higher than expected. Most such regions
      contained either T-cell (CD8(+) CTL or CD4(+) Helper) or B-cell epitopes, or both
      of them simultaneously. The gained knowledge was applied in designing a synthetic
      immunogen containing multiple CTL epitopes. The synthesis of series of chimeric
      peptides representing hypervariable region of V3 loop of HIV envelope, to be used
      as a multi-epitope or mixotope vaccine candidate, has been achieved. Such a
      vaccine could theoretically pre-empt any escape mutant borrowing from antigenic
      diversity of hypervariable region of V3 loop of HIV envelope. CONCLUSIONS: The
      epitopes shared by HIV and its host are likely to be implicated in the
      immunopathogenesis of AIDS through induction of cross-reacting effectors of the
      immune system. The prospect that 'house-keeping' immune mechanism can be foiled
      by molecular mimicry of HIV with physiologically important human proteins should
      be taken into consideration in safer vaccine design.

PMID- 15567092
TI  - Antibodies reactive with C-terminus of the second conserved region of HIV-1gp120
      as possible prognostic marker and therapeutic agent for HIV disease.
AB  - It has been reported that antibodies reactive with peptide
      RSANFTDNAKTIIVQLNQSVEIN (peptide NTM) derived from the C-terminus of the second
      conserved domain of HIV-1 envelope glycoprotein gp120 could represent an
      important factor in control of the HIV disease. In order to check this notion we
      (i) tested reactivity with peptide NTM serum samples collected from 310
      consecutive HIV-1 infected patients with a CD4(+) lymphocyte count ranging from
      10 to 800/microL and (ii) performed the longitudinal study that included 107 sera
      samples collected from 29 HIV patients. Results of these studies demonstrated
      correlation between presence of anti-NTM antibodies in sera of HIV patients and
      disease progression measured by the CD4(+) cell count. Based on these findings we
      proposed the anti-NTM antibodies as useful prognostic marker for HIV disease.

PMID- 15567093
TI  - Monoclonal antibody hNM01 in HIV-infected patients: a phase I study.
AB  - BACKGROUND: hNM01 is a humanized monoclonal antibody that binds to the V(3)
      region of the HIV-1 envelope protein gp120. This binding leads to the activation
      of complement and the disruption of the viral envelope. OBJECTIVES AND STUDY
      DESIGN: The aim of this study was to investigate the clinical responses of the
      individuals when treated with the humanized antibody NMO1. In this phase I study,
      four HIV-1 infected patients with CD4 counts between 50 and 500 cells/mul
      received a total of four doses of hNM01 in an intrapatient dose escalation
      fashion: day 1-0.2 mg/kg, day 15-1 mg/kg, day 29-5 mg/kg, and day 43-5mg/kg.
      Patients were required to have virus that reacted to hNM01 by a virion capture
      assay and to have a viral load > or =15,000 copies/mL. RESULTS AND CONCLUSION:
      The antibody was well-tolerated; no significant adverse events were observed even
      at the highest dose tolerated. None of the patient developed either human anti
      hNM01 (anti-idiotype) or human anti-rat antibodies. The mean elimination half
      life was 153 h (6.4 days). During hNMO1 therapy effects were observed on CD4 cell
      counts and plasma viral loads and further dose finding trials are necessary to
      better determine the therapeutic activity of hNM01 in HIV-infected individuals.

PMID- 15567094
TI  - T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) is frequently associated
      with only partial restoration of CD4 T-cell levels. Autoimmunity to CD4 T-cells
      may account for the persistence of the CD4 T-cell lymphopenia in such cases.
      OBJECTIVE: To document T-cell autoimmunity to CD4 in HIV-infected patients and to
      determine if T-cell vaccination against CD4 autoimmunity is feasible and safe.
      STUDY DESIGN: Seven out of 20 HIV-infected patients undergoing HAART who
      manifested T- cell reactivity to rCD4, gp120 and to recall antigens (Tetanus
      toxoid and Candida) were treated with T-cell vaccines composed of glutaraldehyde
      treated autologous, activated T-cells, and enriched in anti CD4-reactive T-cells.
      The response of the seven vaccinated patients was compared to seven non
      vaccinated HIV-1 infected subjects. RESULTS: Five out of seven responded with a
      decrease in anti-CD4 autoimmunity, associated with a persistent increase in their
      CD4 T-cell levels; just one of the control patients showed increased CD4 levels.
      No change in HIV plasma viral loads and no adverse effects were detected in any
      of the T-cell vaccinated patients. CONCLUSIONS: The persistence of CD4 T-cell
      lymphopenia despite effective anti-retroviral treatment may be associated with
      anti-CD4 autoimmunity. T-cell vaccination with autologous autoimmune CD8 T-cells
      may decrease such autoimmunity and increase CD4 T-cell numbers.

PMID- 15567095
TI  - Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for
      treatment of HIV.
AB  - BACKGROUND: V-1 Immunitor (V1) is an oral AIDS vaccine containing heat- and
      chemically-inactivated viral antigens derived from pooled blood of HIV-positive
      donors. V1 has a pending status as an investigational drug but is currently
      marketed as a dietary supplement. Earlier published, uncontrolled studies of V1
      demonstrated body weight gain, increase in T-lymphocyte numbers, decrease in
      viral load, and improved survival of end-stage AIDS patients. OBJECTIVES AND
      STUDY DESIGN: In order to substantiate prior observations we have undertaken a
      placebo-controlled phase II clinical trial involving 47 antiviral therapy naive,
      asymptomatic individuals who had over 350 mm(3) CD4 T-cells (mean/median 538/480)
      at study entry. Both placebo and treatment arms were identical demographically
      and by every clinical parameter measured at baseline. RESULTS AND CONCLUSIONS: At
      the end of 6-month follow-up 29 volunteers who received V1 b.i.d. had gained on
      average 43 CD4 T-cells (540 versus 583). This gain was statistically significant
      (p=0.01) while changes in T-cell numbers in placebo group failed to reach the
      significance threshold (p=0.33). The clinical potential of V1 is further
      supported by an elevation in CD4/CD8 ratio among V1 recipients and decline in
      CD4/CD8 ratio in patients on placebo (0.575 versus 0.524; p=0.02). The average
      weight gain among patients on V1 was 1.8 kg while placebo group lost 0.5 kg.
      These results suggest that V1 may delay or reverse the disease progression
      without any concurrent toxicity and support our prior open-label studies
      indicating that V1 confers clinical benefit. A phase III clinical study is
      required to confirm these findings and to allow us to seek license for V1 as a
      therapeutic AIDS vaccine.

PMID- 15567096
TI  - Oral immune regulation: a novel method for modulation of anti-viral immunity.
AB  - Chronic viral infections, including hepatitis B and C and human immunodeficiency
      virus (HIV) infections, afflict a significant part of the world's population. In
      many of these diseases, chronicity has been linked to defective anti-viral
      immunity that damages host tissues without producing viral clearance. Currently
      available therapeutic measures for chronic viral infections are limited. Oral
      immune regulation, the manipulation of immune responses towards antigens by their
      oral administration, is a relatively simple and antigen-specific immune
      modulatory tool. Recent evidence suggests that induction of oral immune
      regulation towards viral antigens may entail a complex immune effect,
      characterized by simultaneous enhancement and suppression of different elements
      of the immune response in a manner that benefits the host. Such manipulation of
      the immune response towards viruses may achieve a combination of upregulated
      specific anti-viral immunity and inhibition of immune-mediated damage. Oral
      immune regulation may prove to be an important addition to the available
      therapeutic arsenal for chronic viral infections.

PMID- 15567097
TI  - Assessment of the relative therapeutic effects of vaccines on virus load and
      immune responses in small groups at several time points: efficacy of mucosal and
      subcutaneous polypeptide vaccines in rhesus macaques exposed to SHIV.
AB  - BACKGROUND: Due to the high cost, subject availability and ethical constraints,
      it is often critically important in pre-clinical and clinical studies to carry
      out an adequate statistical analysis of longitudinal multivariate data over
      several time points in trials in several small groups. OBJECTIVES: We aim to
      accurately assess and develop an appropriate distribution-free longitudinal model
      for an estimate of the comparative treatment effects of several biological
      factors in several small groups even if data sets should contain outlier
      measurements and censored values. This approach is used to evaluate the relative
      efficacy of mucosal and subcutaneous polypeptide vaccines in rhesus macaques
      exposed to SHIV. STUDY DESIGN: The algorithms of the non-parametric repeated
      measures ANOVA models [Mack GA. A quick and easy distribution-free test for main
      effects in a two-factor ANOVA. Communic Stat Part B: Simp Comp 1981;10:571-91;
      Akritas MG, Brunner, E. A unified approach to rank tests for mixed models. J Stat
      Plan Inference 1997;61:249-77; Brunner E, Puri ML. Nonparametric methods in
      factorial designs. Stat Pap 2001;42:1-52.] are described, programmed and
      assessed. The viral loads, CD4(+) and CD8(+) cell counts were analyzed at several
      time points in peripheral blood of the 11 MamuA(*)01 positive macaques
      intrarectally challenged with pathogenic SHIV-Ku2 and immunized intrarectally
      with synthetic HIV/SIV peptide vaccine. RESULTS: Using nonparametric ANOVA tests,
      we demonstrated with statistical significance that after intrarectal challenge
      with pathogenic SHIV-Ku2, intrarectally immunized monkeys expressed viral titers
      that fell below the level of detection in blood and intestine (which is a major
      reservoir of viral replication), whereas the subcutaneously immunized or control
      macaques had residual viraemia. Moreover, the proliferative response of T cells
      and both CD4(+) and CD8(+) cells were better preserved in intrarectally immunized
      animals. Robustness of the comparisons was confirmed by gradual removal of up to
      50% of data points. CONCLUSION: Despite limited data, our analysis shows better
      preservation of both CD4(+) and CD8(+) cells in intrarectally immunized animals.
      The result is consistent with our hypothesis that mucosal immunization is more
      effective than systemic immunization and that an induction of specific CTLs in
      the intestinal mucosa, a key site of virus replication, with a mucosal AIDS
      vaccine ameliorates SHIV infection in non-human primates. Our analytical
      methodology can be applicable in comparative estimates of the different treatment
      associated effects and their synergy for a variety of longitudinal data sets in
      small treatment groups.

PMID- 15567098
TI  - Small animal model of HIV-1 infection.
AB  - BACKGROUND: The lack convenient and inexpensive small animal model of HIV
      infection hampers significantly the research on immunopathogenesis, antiviral
      drugs, and vaccines. OBJECTIVES: Development of HIV model in small animals, i.e.,
      cotton rats, was undertaken. STUDY DESIGN: Cotton rats of both sexes were exposed
      to highly replicating HIV-1(zmb) strain by intraperitonial and retrobulbar
      routes. The infection was evaluated by morphological and clinical criteria and by
      amplification of HIV DNA integrated in animal tissues. RESULTS: Six months after
      intraperitoneal infection the lymphoid tissues of all inoculated animals
      exhibited integrated proviral DNA. Despite viral integration no active systemic
      HIV replication was observed. Brain and spleen morphological changes indicated
      the presence of the inflammatory reaction, which was followed by a degenerative
      process. Clinical manifestations of the infection, while varied, revealed
      relative weight loss at three months after infection; apparent respiratory
      disorders; and death of some animals with signs of cachexia and alopecia.
      CONCLUSIONS: Clinical, morphological, and virology assessment of infected animals
      indicate that the virus crosses the interspecies barrier and cotton rats can be
      used as a small animal model of HIV infection.

PMID- 15567099
TI  - Limited cross-reactivity between different HIV-1 clades.
AB  - BACKGROUND: The past two decades has seen an extensive search for a vaccine to
      curtail the HIV/AIDS pandemic. The prevailing opinion is that an HIV vaccine
      should elicit broadly cross-neutralizing antibodies and cellular immune responses
      against primary isolates from divergent clades. The majority of subunit or
      protein based vaccines currently in clinical trials are based on HIV-1 envelope
      proteins mainly derived from subtypes B/A. This has serious implications for
      developing nations where the pandemic is caused by HIV-1 subtype C. This study
      was undertaken considering speculation on the potential cross-reactivity between
      antigens derived from--and immune responses induced by different viral subtypes.
      OBJECTIVES: We report our observations after Galanthus nivalis affinity
      purification of recombinant HIV envelope proteins (CHO gp120/140/160) derived
      from subtypes B/A and using these purified proteins as antigens in ELISA assays
      (against subtype C induced antibodies). RESULTS AND CONCLUSIONS: Polyclonal
      antibodies from HIV-1 subtype C infected HIV/AIDS patients recognized the
      recombinant antigens at varying antibody titers (100-1000). Prior to ELISA
      assays, routine SDS-PAGE and N-terminal sequencing confirmed the identity of the
      purified proteins while their ability to induce apoptosis confirmed their
      functionality. The purified proteins were also used to elicit polyclonal
      antibodies in mice, which recognized the immunogens as antigen in ELISA assays at
      titers of 500-5000, and cross-reacted at lower antibody titers.

PMID- 15567100
TI  - The effect of iron overload on in vitro HIV-1 infection.
AB  - BACKGROUND: It has been shown that Fe is required by HIV-infected cells for
      production of viral particles. Excess iron in the cell is detrimental to the host
      but beneficial to the pathogen. OBJECTIVES: Here, we investigated the effect of
      excess Fe (overload) and chelation of the metal on in vitro HIV infection by
      assessing host cell responses (viability/death, stress protein expression and
      cytokine production) as well as virus replication (core protein content and
      enzyme activity). RESULTS AND CONCLUSION: Excess iron decreased viability (21%,
      P<0.01) of HIV-infected cells, increased p24 levels by 8.6% (P=0.32) and elevated
      reverse transcriptase (RT) activity (81.7%, P<0.01). The stimulation of viral
      replication was decreased when Fe was first complexed to desferrioxamine (DFO).
      DFO alone (in the absence of excess Fe), lowered cell viability (35%, P=0.039)
      and in the presence of virus lowered both p24 levels (66%, P=0.054) and RT
      activity (43%, P<0.01) and unexpectedly increased cell viability (25%,
      P=0.01047). Interleukin-2 (IL-2) production of infected cells was completely
      inhibited by DFO and excess iron while stress protein (Hsp70) levels were lowered
      in the presence of HIV in combination with excess iron (37%, P<0.01) or DFO
      (47.2%, P<0.01) when compared to untreated cells. According to flow cytometric
      data, HIV infection caused a two-fold increase in the numbers of necrotic
      (P=0.006) and decreased apoptotic cells (28.5%, P=0.15) cells. These findings
      indicate that Fe overload associated with HIV infection is detrimental to host
      cell responses against viral infection and that chelation can prevent and/or
      reverse this effect.

PMID- 15567101
TI  - Intranasal immunization with liposome-encapsulated plasmid DNA encoding influenza
      virus hemagglutinin elicits mucosal, cellular and humoral immune responses.
AB  - BACKGROUND: Influenza viral infections are a significant global public health
      concern due to the morbidity and mortality associated with acute respiratory
      disease, associated secondary complications and pandemic threat. Currently, the
      most effective preventative measure is an annual intramuscular (i.m.) injection
      of a trivalent vaccine. Intramuscular immunization induces strong systemic
      humoral responses but not mucosal immune responses which are important in the
      first line of defense against influenza. OBJECTIVES: A plasmid encoding influenza
      A/PR/8/34 (H1N1) hemagglutinin (HA; pCI-HA10) was evaluated with respect to the
      mucosal, cellular and humoral immune responses generated and to its efficacy in
      protection against a challenge with a lethal dose of influenza. STUDY DESIGN:
      BALB/c mice were immunized with pCI-HA10 DNA or liposome-encapsulated pCI-HA10 by
      either an intranasal (i.n.) or i.m. route. Sera and bronchoalveolar lavage (BAL)
      fluid were collected at various times and evaluated for HA-specific IgG and IgA
      antibodies and T cells, isolated from draining lymph nodes and spleens, were
      analyzed for their proliferative ability. Immunized mice were challenged with a
      lethal dose (5LD(50)) of influenza and monitored for survival. RESULTS AND
      CONCLUSIONS: Intranasal immunization with liposome-encapsulated pCI-HA10
      stimulated both IgG and IgA humoral responses and increased IgA titers in BAL
      fluid, whereas immunization with naked pCI-HA10 had no effect on the antibody
      response. Intramuscular immunization with both naked and liposome-encapsulated
      pCI-HA10 elevated serum IgG levels, but had no effect on IgA levels in either the
      serum or BAL fluid. Both i.n. and i.m. administration of HA vaccine (naked and
      liposome-encapsulated) elicited T cell proliferative responses. These results
      suggest that i.n. administration of liposome-encapsulated HA-encoding DNA is
      effective at eliciting mucosal, cellular and humoral immune responses. Mice
      immunized i.n. were able to withstand a lethal challenge of influenza virus,
      confirming that the immune responses mediated by the vaccine were protective.

PMID- 15567102
TI  - Effect of surface roughness of ground titanium on initial cell adhesion.
AB  - The effect of surface roughness of ground Ti on the initial adhesion of
      osteoblast-like U-2 OS cells was investigated in this study. Different numbers
      (#120, #600, and #1500) of SiC sandpaper and two Al2O3 polishing powder (0.3 and
      1 microm) were used to prepare the metal specimens with varying degrees of
      surface roughness. Surface roughness (Ra) was measured by profilometry. Surface
      topography was observed using an atomic force microscope. MTT (3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was used to measure
      the optical density (OD) of specimens after 2 h of cell incubation. The OD value
      was analyzed by one-way ANOVA for analyzing the factor of surface roughness.
      Crystal violet staining technique was used to characterize the cell spreading.
      Results showed that the specimen of #1500 Ti (Ra: 0.15 microm) had the highest OD
      value. The specimens polished with 0.3 and 1 microm Al2O3 powder (Ra: 0.05 and
      0.07 microm) exhibited the worst cell adhesion behavior. Contact guidance of
      cells could be observed on the rougher #600 and #120 specimens (Ra: 0.33 and 1.20
      microm). This study concludes that the surface roughness (Ra: 0.05-1.20 microm)
      of ground Ti has a highly significant influence on the initial adhesion of
      osteoblast-like U-2 OS cells. The ground Ti with an Ra of 0.15 microm shows the
      optimal cell adhesion behavior with respect to either the rougher or smoother
      specimens.

PMID- 15567103
TI  - Bioeffect of ultrasound on endothelial cells in vitro.
AB  - The effects of low-intensity ultrasound (US) on biological systems have been
      investigated extensively; however, the effects of ultrasound stimulation on
      endothelial cells were rarely studied. In this study, 1 MHz, pulsed 1:4, and four
      different spatial-average temporal-peak intensities (0.5, 1.0, 1.6, and 2W/cm2)
      of ultrasound were used to stimulate endothelial cells for 10 min per day. The
      results showed that ultrasound (intensity 1.6-2.0W/cm2) treatment after 6 days
      enhanced the nitric oxide (NO) and Ca2+ release from the endothelial cells but
      did not promote cell growth. In addition, ultrasound stimulation changed the
      cellular morphology and orientation, and increased extracellular matrix secretion
      from endothelial cells.

PMID- 15567104
TI  - Adherence of Staphylococcus aureus fibronectin binding protein A mutants: an
      investigation using optical tweezers.
AB  - Bacterial adhesion to extracellular matrix proteins plays a major role in
      infections of host tissue and medical devices. In some species of gram-positive
      cocci, this adhesion is mediated by specific molecules present on the bacterial
      cell surface. We have used optical tweezers to dynamically measure the adhesive
      force between an individual Staphylococcus aureus bacterium and a fibronectin
      coated surface. A bacterium was optically trapped and brought in contact with a
      10-microm diameter polystyrene microsphere coated with fibronectin. The force
      required to detach the cell from the microsphere was measured by tracking the
      displacement signals of the trapped cell on a quadrant photodiode throughout the
      detachment process for a series of S. aureus strains expressing fibronectin
      binding proteins with various degrees of mutation. The single-bond rupture forces
      ranged between 15 and 26 pN depending on the extent of mutation. No binding was
      observed in the strain with the highest degree of mutation. These results confirm
      that multiple regions of the S. aureus fibronectin adhesin participate in the
      binding process and provide further insight into the role of these regions in the
      adhesive process.

PMID- 15567105
TI  - RNA interference: PCR strategies for the quantification of stable degradation
      fragments derived from siRNA-targeted mRNAs.
AB  - mRNA targeted by siRNA is endogeneously cleaved into a 5'- and a 3'-fragment and
      finally degraded in cells. Little is known about the relative stability and
      degradation kinetics of these 5'- and 3'-fragments after the siRNA mediated first
      cut. We present a qRT-PCR protocol which allows the determination of the optimal
      time point for mRNA analyses, helping to avoid the generation of false positive
      effects in downstream experiments, such as microarray analysis, which may be
      caused by undegraded fragments of a siRNA-targeted mRNA.

PMID- 15567106
TI  - Are romantic partners a source of college students' weight concern?
AB  - This study explored the importance of weight in college students' dating
      relationships and the expression of weight-related concerns between dating
      romantic partners. In a survey of 554 undergraduates, we found that overweight
      women were less likely to be dating than their peers, and that weight was
      positively correlated with relationship satisfaction in men, but negatively
      correlated with satisfaction in women. We also found that over 30% of students in
      exclusive relationships had either been told by their partner (or had told their
      partner) to gain or lose weight. While male partners were typically told to gain
      weight, female partners were as likely to be told to lose as gain weight. Women's
      weight-loss attempts and self-esteem were not related to being the targets of
      these comments, but women told to lose weight reported lower relationship
      satisfaction; men's self-esteem was not related to being the targets of these
      comments, but men told to gain weight reported lower relationship satisfaction.
      Although our results support prior research suggesting that weight is
      differentially important for men and women in romantic relationships, they
      challenge the hypothesis that individual romantic partners are a primary source
      of students' body dissatisfaction and weight concerns.

PMID- 15567107
TI  - Biological, psychological, and sociocultural correlates of body change strategies
      and eating problems in adolescent boys and girls.
AB  - The present study examines correlates of body change strategies and eating
      problems in youths. A large sample of adolescents aged 12 to 16 years (N = 307)
      was asked to complete a set of questionnaires, which measured biological (age,
      pubertal status, and body mass index [BMI]), psychological (self-esteem, body
      dissatisfaction, body importance, and body comparison), and sociocultural
      variables (influence of media, parents, and peers), as well as body change
      strategies and disturbed eating attitudes and behaviors. Results showed that boys
      generally try to become more muscular, whereas girls attempt to lose weight.
      Further, correlational and regression analyses demonstrated that biological,
      psychological, and sociocultural influences made unique and significant
      contributions to various body image and body change/eating problems variables.
      Finally, hierarchical regression analyses yielded theoretically meaningful models
      for the main body change strategies in boys and girls. In these models, BMI, self
      esteem, and sociocultural influences turned out to be significant predictor
      variables, while body-image-related factors, and in particular body comparison
      (i.e., the tendency to compare one's body with that of others), partially or
      fully mediated the influence of some predictor variables.

PMID- 15567108
TI  - Influences of ethnicity and socioeconomic status on the body dissatisfaction and
      eating behaviour of Australian children and adolescents.
AB  - The present study examined the association between socioeconomic status (SES),
      ethnicity, body dissatisfaction, and eating behaviours of 10- to 18-year-old
      children and adolescents. The study participants (N = 768) were categorised as
      Caucasian (74.7%), Chinese or Vietnamese (18.2%), and Italian or Greek (7.0%),
      and high (82%), middle (8.6%), and low SES (9.4%) according to parents'
      occupations. The chi(2), Mann-Whitney U test and Kruskal-Wallis test and logistic
      regression model were used to determine the interaction between variables.
      Females and older participants were more likely to desire a body figure that was
      thinner than their perceived current figure. Furthermore, the same groups were
      also more likely to be preoccupied with eating problems (females 7.1% vs. males
      1.4%; for participants aged 15-18 years, 7.8% vs. participants aged 10-14 years,
      3.9%). The body dissatisfaction gender difference was females 42.8% vs. males
      11.8%, and participants aged 15-18 years 41.7% vs. those aged 10-14 years, 28.3%.
      Participants whose parents were managers/professionals were more likely to desire
      a body figure that was thinner than their perceived current figure than those
      from white-collar and blue-collar families. This was also the case for Caucasian
      Australians compared to those from Chinese or Vietnamese backgrounds. In
      conclusion, age and gender differences in body image and problems in eating
      behaviour were evident among children and adolescents. However, there was no
      significant SES and ethnic difference in the proportion of participants with
      eating problems and body dissatisfaction.

PMID- 15567109
TI  - Binge eating and psychological distress: is the degree of obesity a factor?
AB  - The purpose of the present study was to examine whether individuals with Binge
      Eating Disorder (BED) demonstrate comparable levels of eating pathology and
      psychological distress independent of weight status. Male and female participants
      with BED (N = 96) completed the Questionnaire on Eating and Weight Patterns
      Revised; Beck Depression Inventory (BDI), Symptom Checklist (SCL)-90-Revised, and
      Eating Disorder Inventory-2 (EDI-2). Participants were divided into categories of
      normal/overweight, obese, and severely obese based on their body mass index
      (BMI). Analysis of variance was performed using scores on the psychological
      measures with subjects grouped according to weight status. Participants with BED
      did not differ on any of the measures of psychological or eating symptoms
      regardless of weight status. These results replicate and extend previous
      findings, suggesting that binge eating pathology independent of weight status,
      accounts for psychological distress among binge eaters.

PMID- 15567110
TI  - Pathological dieting and alcohol use in college women--a continuum of behaviors.
AB  - The relationship between dieting and bingeing severity and alcohol use was
      studied in a sample of women in their first year of college (n = 1384). The study
      was designed to replicate and extend earlier findings of a graded positive
      relationship between the dieting and bingeing severity and the frequency,
      intensity, and negative consequences of alcohol use in young women, while
      adjusting for known predictors of alcohol use. Prevalence of past month alcohol
      use, drinking enough to get high on half or more drinking occasions, and heavy
      drinking (>or= five drinks in a row) in these women were positively associated
      with dieting and bingeing severity in a graded manner across the entire range of
      these behaviors. Dieting and bingeing severity was also more closely associated
      with the frequency and intensity of alcohol use than measures of depression,
      parents' drinking level, and early age of first drink. Finally, dieting and
      bingeing severity was positively associated with the prevalence of negative
      consequences of alcohol use, such as blackouts and unintended sexual activity.
      These results suggest that the dysfunctional eating behaviors often associated
      with dieting could also be associated with dysfunctional alcohol use.

PMID- 15567111
TI  - Empirical classification of eating disorders.
AB  - Although the eating disorder nosology has become refined over the years,
      considerable problems remain. The purpose of the present study was to empirically
      examine eating disorder classification using a sample of treatment-seeking eating
      disorder patients. One hundred and fifty-nine patients with diagnoses of anorexia
      nervosa (AN), bulimia nervosa (BN), and eating disorder, not otherwise specified
      (EDNOS), were included in a cluster analysis using a variety of eating disorder
      variables. Findings revealed four clusters, with three clusters resembling AN,
      restricting type, BN, and binge-eating disorder (BED). The remaining cluster
      appeared to be a group of patients that were subthresholded in terms of symptom
      severity. Results also indicated a relatively poor fit between the empirically
      derived groupings and clinical diagnoses. The implications of these findings for
      both the current classification system and treatment considerations are
      discussed.

PMID- 15567112
TI  - Night eating syndrome: evaluation of two screening instruments.
AB  - The purpose of the present study was to determine whether night eating syndrome
      was associated with treatment outcomes during a brief weight loss intervention
      for self-identified night snackers, and to evaluate the diagnostic utility of a
      screening question and the Night Eating Syndrome Questionnaire (NESQ) for the
      detection of night eating syndrome. Participants enrolled in a 4-week randomized
      clinical trial for obese and overweight persons who self-identified as night
      snackers were administered a structured clinical interview, a night eating
      screening question, and the NESQ. Treatment outcomes included adherence and
      weight loss. Results showed that night eating syndrome diagnoses were not
      associated with treatment outcomes. The screening question had adequate
      sensitivity but poor specificity. The night eating questionnaire was positively
      correlated with increasingly stringent definitions of night eating syndrome.
      Night eating syndrome is not the equivalent of night snacking. The definition of
      night eating syndrome must be expanded to include a sleep disturbance component
      accompanied by night eating.

PMID- 15567113
TI  - The effects of modeling dietary restraint on food consumption: do restrained
      models promote restrained eating?
AB  - Sixty-nine female undergraduates completed the restraint scale, a dieting
      checklist, and the Eating Attribution Style Questionnaire (EASQ). The
      participants were exposed either to no model, a peer model who behaviorally
      demonstrated dietary restraint, or a peer model who behaviorally and verbally
      demonstrated dietary restraint. The participants had an opportunity to consume
      food as part of a taste test. The findings revealed that attribution style, but
      not restraint or current dieting status, moderated the effects of exposure to the
      peer models. Females who had an internal attribution style for indulgent food
      consumption decreased their consumption of food as a function of the dietary
      restraint of the models, whereas females who had an external attribution style
      for indulgent food consumption increased their consumption of food as a function
      of the dietary restraint of the models. The latter disinhibitory effect was
      attributed to negative social comparison and learned helplessness. The results
      supported the conclusion that the effectiveness of modeling dietary restraint is
      dependent on the attribution style of the observers.

PMID- 15567114
TI  - Test-retest reliability and discriminant validity of the Restraint Scale
      translated into Portuguese.
AB  - The aim of this study was to evaluate reliability and discriminant validity of
      the Restraint Scale (RS) translated into Portuguese. The version was obtained
      through a process of translation and back translation. Women with eating
      disorders (n = 39: 24 bulimics and 15 anorexics) and students without eating
      disorders (n = 57) filled the scale. It was hypothesized that if the scale has
      any discriminant validity, the bulimic scores should differ from those of the
      students and the anorexics. The questionnaire was applied twice to the controls
      with 1-month interval to evaluate test-retest stability. Bulimics obtained a
      score of 28.1 +/- 13 (significantly different from students and anorexics),
      anorexics obtained 17.3 +/- 9 (significantly different from students), and
      students 11.3 +/- 5. Body mass index (BMI) was significantly correlated to
      dietary restraint, especially among controls. Test-retest correlation coefficient
      was .64 (P = .000001). The RS translated into Portuguese seems to be a valid and
      reliable instrument, which can be used in many studies of eating behaviors.

PMID- 15567115
TI  - Comparison of child interview and parent reports of children's eating disordered
      behaviors.
AB  - Self-report questionnaires of child eating behavior have demonstrated poor
      agreement with child interview methods and parent report. However, no study has
      investigated the relationship between child interview and parent report.
      Therefore, we compared results from a diagnostic interview, the Eating Disorder
      Examination adapted for Children (ChEDE) to those from a questionnaire, the
      Adolescent Version of the Questionnaire on Eating and Weight Patterns-parent
      version (QEWP-P), in a nontreatment sample of overweight and normal weight
      children. Both instruments were administered to 88 overweight (BMI >or= 85th
      percentile) and 79 normal weight (BMI<85th percentile) children, age 10.2 +/- 1.7
      years, recruited from the community. The ChEDE and QEWP-P were not concordant in
      terms of the type of eating episodes that occurred in the past month. Using the
      ChEDE as the criterion method, the QEWP-P had reasonably high specificity, but
      low sensitivity for the presence of binge episodes (sensitivity 50%, specificity
      83%) or objective overeating (sensitivity 30%, specificity 79%) during the past
      month. ChEDE subscales were, however, significantly related to items assessing
      eating-related distress on the QEWP-P. While parent report of child eating
      behaviors may provide some general information regarding eating psychopathology
      in young nontreatment-seeking children, they do not accurately reflect the
      results of a structured interview.

PMID- 15567116
TI  - Hospital hygiene sweeps resistance under the carpet.

PMID- 15567117
TI  - Amodiaquine during pregnancy.

PMID- 15567118
TI  - Nosocomial infection: a terminological clarification.

PMID- 15567120
TI  - Favourite papers in infectious diseases 2004.

PMID- 15567122
TI  - Human cytomegalovirus: clinical aspects, immune regulation, and emerging
      treatments.
AB  - After initial infection, human cytomegalovirus remains in a persistent state with
      the host. Immunity against the virus controls replication, although intermitent
      viral shedding can still take place in the seropositive immunocompetent person.
      Replication of cytomegalovirus in the absence of an effective immune response is
      central to the pathogenesis of disease. Therefore, complications are primarily
      seen in individuals whose immune system is immature, or is suppressed by drug
      treatment or coinfection with other pathogens. Although our increasing knowledge
      of the host-virus relationship has lead to the development of new pharmacological
      strategies for cytomegalovirus-associated infections, these strategies all have
      limitations-eg, drug toxicities, development of resistance, poor oral
      bioavailability, and low potency. Immune-based therapies to complement
      pharmacological strategies for the successful treatment of virus-associated
      complications should be prospectively investigated.

PMID- 15567123
TI  - Human genetics of intracellular infectious diseases: molecular and cellular
      immunity against mycobacteria and salmonellae.
AB  - The ability to develop adequate immunity to intracellular bacterial pathogens is
      unequally distributed among human beings. In the case of tuberculosis, for
      example, infection with Mycobacterium tuberculosis results in disease in 5-10% of
      exposed individuals, whereas the remainder control infection effectively. Similar
      interindividual differences in disease susceptibility are characteristic features
      of leprosy, typhoid fever, leishmaniasis, and other chronic infectious diseases,
      including viral infections. The outcome of infection is influenced by many
      factors, such as nutritional status, co-infections, exposure to environmental
      microbes, and previous vaccinations. It is clear, however, that genetic host
      factors also play an important part in controlling disease susceptibility to
      intracellular pathogens. Recently, patients with severe infections due to
      otherwise poorly pathogenic mycobacteria (non-tuberculous mycobacteria or
      Mycobacterium bovis BCG) or Salmonella spp have been identified. Many of these
      patients were unable to produce or respond to interferon gamma, due to
      deleterious mutations in genes that encode major proteins in the type 1 cytokine
      (interleukin 12/interleukin 23/interferon gamma) axis (interleukin
      12p40/interleukin 23p40, IL12 receptor beta1/IL23 receptor beta1, interferon
      gamma receptors 1 and 2, or signal transducer and activator of transcription 1).
      This axis is a major immunoregulatory system that bridges innate and adaptive
      immunity. Unusual mycobacterial infections were also reported in several patients
      with genetic defects in inhibitor of NFkappaB kinase gamma, a key regulatory
      molecule in the nuclear factor kappaB pathway. New findings discussed in this
      review provide further and sometimes surprising insights into the role of type 1
      cytokines, and into the unexpected heterogeneity seen in these syndromes.

PMID- 15567124
TI  - Idiopathic pneumothorax, or not?

PMID- 15567125
TI  - New developments in the diagnosis of bloodstream infections.
AB  - New techniques have emerged for the detection of bacteria in blood, because the
      blood culture as gold standard is slow and insufficiently sensitive when the
      patient has previously received antibiotics or in the presence of fastidious
      organisms. DNA-based techniques, hybridisation probes, and PCR-based detection or
      protein-based detection by mass spectroscopy are aimed at rapid identification of
      bacteria and provide results within 2 h after the first signal of growth in
      conventional blood cultures. Also, detection of microorganisms directly in blood
      by pathogen-specific or broad-range PCR assays (eubacterial or panfungal) shows
      promising results. Interpretation is complex, however, because of detection of
      DNA rather than living pathogens, the risk of interfering contamination, the
      presence of background DNA in blood, and the lack of a gold standard. As these
      techniques are emerging, clinical value and cost-effectiveness have to be
      assessed. Nevertheless, molecular assays are expected eventually to replace the
      current conventional microbiological techniques for detection of bloodstream
      infections.

PMID- 15567126
TI  - Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic
      review.
AB  - A major challenge in tuberculosis control is the diagnosis and treatment of
      latent tuberculosis infection. Until recently, there were no alternatives to the
      tuberculin skin test (TST) for diagnosing latent tuberculosis. However, an
      alternative has now emerged in the form of a new in-vitro test: the interferon
      gamma assay. We did a systematic review to assess the performance of interferon
      gamma assays in the immunodiagnosis of tuberculosis. By searching databases,
      contacting experts and test manufacturers, we identified 75 relevant studies. The
      results suggest that interferon-gamma assays that use Mycobacterium tuberculosis
      specific region of difference 1 (RD1) antigens (such as early secretory antigenic
      target 6 and culture filtrate protein 10) may have advantages over the TST, in
      terms of higher specificity, better correlation with exposure to M tuberculosis,
      and less cross-reactivity due to BCG vaccination and non-tuberculous
      mycobacterial infection. However, interferon-gamma assays that use RD1 antigens
      in isolation may maximise specificity at the cost of sensitivity. Assays that use
      cocktails of RD1 antigens seem to overcome this problem, and such assays have the
      highest accuracy. RD1-based interferon-gamma assays can potentially identify
      those with latent tuberculosis who are at high risk for developing active
      disease, but this requires confirmation. There is inadequate evidence on the
      value of interferon-gamma assays in the management of immunocompromised
      individuals, children, patients with extrapulmonary or non-tuberculous
      mycobacterial disease, and populations in countries where tuberculosis is
      endemic. Current evidence suggests that interferon-gamma assays based on
      cocktails of RD1 antigens have the potential to become useful diagnostic tools.
      Whether this potential can be realised in practice remains to be confirmed in
      well designed, long-term studies.

PMID- 15567127
TI  - A mechanic with a bad valve: blood-culture-negative endocarditis.
AB  - A 33-year-old man with a known bicuspid aortic valve presented with fever,
      chills, progressive fatigue, anorexia, and night sweats. Echocardiography
      confirmed aortic-valve endocarditis, but blood cultures remained negative.
      Bartonella henselae endocarditis was ultimately confirmed by serology as well as
      by immunohistochemistry and PCR testing of the excised valve. The patient
      recovered with appropriate antibiotic therapy. B henselae is a common cause of
      culture-negative endocarditis. It predominantly affects men with underlying
      valvular disease, and has a predilection for aortic valves. Diagnosis is usually
      made serologically and with either tissue culture, immunohistochemistry, or PCR.
      Treatment of this destructive endocarditis consists of a combination of long-term
      antibiotic therapy and surgical valve repair. This case is used to discuss the
      approach towards the treatment of patients with endocarditis that is blood
      culture negative.

PMID- 15567128
TI  - David Heymann--WHO's public health guru. Interview by Haroon Ashraf.

PMID- 15567132
TI  - Training for bacteria.

PMID- 15567133
TI  - Bacteriophage-encoded type III effectors in Salmonella enterica subspecies 1
      serovar Typhimurium.
AB  - Salmonella spp. are Gram-negative bacteria which cause infections ranging from
      mild, self-limiting enterocolitis to systemic (typhoid) disease. Recent work has
      established that the genetic makeup varies considerably between different
      Salmonella strains. Phages play an important role in this diversity. In fact,
      Salmonella has emerged as a prime example for the involvement of virulence factor
      encoding phages in the emergence of new epidemic strains. Among other virulence
      factors, Salmonella enterica utilizes two specialized protein secretion systems
      termed type III secretion systems (TTSS) to deliver effector proteins into host
      cells which manipulate host cell signaling cascades. These two TTSS and several
      effectors are encoded within Salmonella pathogenicity islands 1 and 2. Some
      effectors including SopE, SspH1, SseI and SopE2 are encoded by phages or phage
      remnants. These phage-encoded effectors seem to be transferred between different
      Salmonella strains. They have attracted much interest because they might
      contribute to the evolution of Salmonella spp. Here we will focus on SopEPhi
      which encodes the SPI-1 effector SopE. It provides an excellent example to
      illustrate how horizontally transferred effector proteins are integrated into the
      complex regulatory network of a TTSS in a recipient bacterium. Additional data
      supporting the hypothesis are presented. This is a prerequisite to allow
      optimization of the bacterium host cell interaction by reassortment of the phage
      encoded effector protein repertoire.

PMID- 15567134
TI  - theta-Defensin pseudogenes in HIV-1-exposed, persistently seronegative female sex
      workers from Thailand.
AB  - The leukocytes of rhesus monkeys contain cyclic octadecapeptides (theta;
      defensins) that can protect cells from infection by HIV-1 in vitro. Although
      humans express mRNA from one or more theta;-defensin pseudogenes, these
      transcripts contain a premature stop codon that prevents formation of theta;
      defensin peptides. We hypothesized that some highly exposed persistently
      seronegative (HEPS) individuals might have intact theta;-defensin (DEFT) genes
      and produce functional theta;-defensins that might account for their resistance
      to HIV-1 infection. We sequenced DEFT genes from 30 women in Chiang Rai, northern
      Thailand: 11 HEPS female sex-workers and 19 control women (10 HIV-1 infected and
      9 HIV-1 uninfected). We found that theta;-defensin genes from all 11 HEPS women
      contained the crucial signal sequence stop codon, as did the 19 control women.
      Synthetic theta;-defensins based on the cDNA sequences to generate a human theta;
      defensin (termed retrocyclin-1 and -2) were capable of inhibiting replication of
      Thai HIV-1 subtype B and CRF01_AE isolates regardless of the coreceptor
      utilization of the isolates. Although our study indicates that synthetic theta;
      defensin peptides are effective in vitro against Thai subtype B and CRF01_AE
      isolates of HIV-1, the presence of premature stop codons in the DEFT genes of
      these HEPS women makes it unlikely that endogenous theta;-defensin production
      accounts for their resistance to HIV-1.

PMID- 15567135
TI  - Internal transcribed spacers (ITS) of Trypanosoma rangeli ribosomal DNA (rDNA): a
      useful marker for inter-specific differentiation.
AB  - The internal transcribed spacers (ITS) flanking the 5.8S subunit of the ribosomal
      RNA genes (rDNA) of Trypanosoma rangeli strains isolated from distinct
      geographical regions and hosts were studied. The results revealed the sequence
      variability of the ITS spacers showing the presence of microsatellite repeats and
      single nucleotide polymorphisms (SNP), which were also observed within the 5.8S
      rDNA sequence. ITS-2 spacer was the most phylogenetically informative region due
      the presence of a higher number of parsimonious sites in both inter- and intra
      specific analysis. Sequence analysis of both ITS spacers plus the 5.8S rDNA of T.
      rangeli strains allowed a clear inter-specific differentiation from Trypanosoma
      cruzi strains representative of the parasite zymodemes.

PMID- 15567136
TI  - Sudanese mucosal leishmaniasis: isolation of a parasite within the Leishmania
      donovani complex that differs genotypically from L. donovani causing classical
      visceral leishmaniasis.
AB  - Mucosal leishmaniasis, which is a sporadic disease in the Sudan, was shown by
      isoenzyme characterization and PCR to be caused by Leishmania donovani. However,
      it was not clear if the parasite was exactly the same strain as that causing
      visceral leishmaniasis (VL), or of a different strain. We utilized a new
      generation of molecular DNA markers, minisatellites and kinetoplast DNA, for
      rapid characterization of the parasite. The results show that the genotypes of
      some of the parasites causing VL are different from those causing mucosal
      leishmaniasis. The L. donovani isolates causing visceral disease, as well as post
      kala-azar mucosal leishmaniasis (PKML), have been shown to possess characteristic
      haplotypes. However, sequencing of a portion of the cytochrome oxidase II (COII)
      gene indicates that the parasite that invades the oral mucosa is divergent from
      other parasites causing VL. It appears to possess features of a more ancestral
      parasite with pronounced sequence homology to L. major. This agrees with earlier
      studies where isolates of mucosal leishmaniasis have been shown to possess an
      isoenzyme profile distinct from L. donovani and a different geographical
      distribution, albeit often overlapping with that of L. donovani.

PMID- 15567137
TI  - Methods of quantifying and visualising outbreaks of tuberculosis using genotypic
      information.
AB  - Genotypic data from pathogenic isolates are often used to measure the extent of
      infectious disease transmission. These methods include phylogenetic
      reconstruction and the evaluation of clustering indices. The first aim of this
      paper is to critique current methods used to analyse genotypic data from
      molecular epidemiological studies of tuberculosis. In particular, by not
      accounting for the mutation rate of markers, errors arise in making inferences
      about outbreaks based on genotypic information. The second aim is to suggest a
      new way to represent genotypic data visually, involving graphs and trees. We also
      discuss some interpretations and modifications of existing indices. Although our
      focus is tuberculosis, the methods we discuss are generally applicable to any
      directly transmissible clonal pathogen.

PMID- 15567138
TI  - Characteristics of HIV-1 env V3 loop sequences for subtype A1 variant spread in
      Eastern Europe.
AB  - OBJECTIVES: The aim of our investigation was to study the HIV-1 env V3 loop
      sequences of the subtype A variant of the virus actively circulating in the
      territory of Eastern Europe (A1-EE). DESIGN: It appears that the characteristics
      of HIV-1 V3 loop sequences of the thoroughly studied subtype B strains determine
      the viruses tropism and phenotype. We were interested to find out to what extent
      these trends are preserved with the subtype A isolates spread in Eastern Europe.
      METHODS: About 474 HIV-1 strains were isolated by cocultivation with
      phytohemagglutinin stimulated and interleukin-2 activated PBMC. Isolates were
      subtyped after distinct regions gag, pol and env were amplified by nested
      polymerase chain reaction. V3 sequences were studied in detail and compared with
      the isolates that appeared as SI or NSI in test-cultures MT-2. RESULTS: The
      subtype A HIV-1 strains spread in Eastern Europe appeared to have V3 loop
      sequences with a high level of conservatism. The consensus sequences of the SI
      and NSI isolates proved identical, and correspond to the phenotype markers of
      subtype B NSI strains. Nevertheless, the subtype A SI isolates induced active
      syncytium-formation processes in the MT-2 test culture. CONCLUSION: The data
      obtained evidenced to the following: the HIV-1 subtype A variant spread in
      Eastern Europe, is capable of using for interaction with receptor structures of
      sensitive cells the tools and mechanisms, which are significantly different from
      those described for subtype B.

PMID- 15567139
TI  - Mode of selection and experimental evolution of antiviral drugs resistance in
      vesicular stomatitis virus.
AB  - The possession of an antiviral resistance mutation benefits a virus when the
      corresponding antiviral is present. But does the resistant virus pay a fitness
      cost when the antiviral is absent? Would an evolutionary history of association
      between a genotype and a resistance mutation overcome this cost by changes
      compensating the harmful side-effect of resistance mutations? Are combined
      therapies more effective against the rise of resistant viruses or against
      evolutionary compensations? To explore all these questions, we took an
      experimental evolution approach. After selecting vesicular stomatitis virus (VSV)
      populations able to replicate under increasing concentrations of ribavirin and/or
      alpha-interferon, we evolved them for more than 100 generations under sub
      inhibitory concentrations of the corresponding antivirals, allowing for
      evolutionary compensation. Our results show that resistance for these two
      antivirals was not easily achieved, being the selected populations generally less
      fit than the ancestrals both in presence and absence of the antivirals. Evolution
      in presence of sub-inhibitory concentrations of antivirals compensated for the
      reduction in fitness in presence of antiviral therapy.

PMID- 15567140
TI  - Differentiation of highly prevalent IS6110 single-copy strains of Mycobacterium
      tuberculosis from a rural community in South India with an ongoing DOTS
      programme.
AB  - We have prospectively analysed the DNA fingerprinting of Mycobacterium
      tuberculosis strains in a rural community from high prevalence area in South
      India with an ongoing DOTS programme. Strains from 451 culture-positive cases,
      diagnosed during July 1999-December 2000, were fingerprinted initially by both
      IS6110 and DR probes followed by polymorphic GC-rich repeat sequences (PGRS)
      typing only on low-copy strains. The results were correlated with selected
      epidemiological and clinical data. Forty one percent of strains showed single
      copy of IS6110, which further got differentiated into 62 DR and 27 PGRS patterns.
      One predominant DR pattern (5B/2) was found in 20% of the low-copy strains and
      was also involved in clusters. In all, 183 patients out of 451 (40%) were
      clustered in total 44 clusters when analysed by IS6110 and DR probes. With
      additional PGRS typing, the number of patients clustered was further reduced to
      106 (23%). More number of patients (131) were clustered in IS6110 single-copy
      group. The maximum number of clusters was found with two or three patients. Only
      a small percentage (16%) of the patients reported direct epidemiological links
      while remaining patients might have had indirect links or casual contacts. Thus,
      a combination of two to three genetic markers is able to differentiate the most
      endemic strains of M. tuberculosis in areas with a high incidence of
      tuberculosis. The epidemiological data do not suggest any major outbreaks or a
      hot-spot hypothesis of transmission in this region. Phylogenetic analysis using
      IS6110, DR and PGRS RFLP (restriction fragment length polymorphism, RFLP)
      fingerprints showed that isolates exhibited clonal evolutionary pattern. The
      predominance of certain genotypes and agreement between the phylogenetic trees
      indicated that these strains were closely related and might have evolved or
      propagated from the common ancestor.

PMID- 15567141
TI  - Distribution of virulence related genes among enteroaggregative Escherichia coli
      isolates: using multiplex PCR and hybridization.
AB  - The importance of enteroaggregative Escherichia coli (EAEC) strains in public
      health around the world is becoming increasingly clear. EAEC diagnosis has long
      been problematic. In this study, the recently designed multiplex PCR based on
      three plasmid-borne genes (AA probe, aap, and aggR) and DNA hybridization assay
      with plasmid-derived DNA probes were used for detection of HEp-2 adherent
      strains. These were isolated from an epidemiologic study of diarrhea in Iran.
      Using AA and DA probes revealed that 32.4%, 16.2%, 23%, and 28.4% of these
      isolates were AA, DA, AA/DA, and non-AA/DA, respectively. However, employing
      multiplex PCR for detection of these isolates, showed that 51.3% of the strains
      were AA and the rest 48.7% were not AA. While presence of other genes (pet, shf,
      aggA, aafA) considered to be specific for EAEC were checked among these isolates.
      The data obtained revealed that except for AA, aap, and aggR, the rest of the
      virulence related genes are not specific for EAEC isolates and are randomly
      distributed among adherent isolates. Over all the results obtained here indicated
      that this multiplex PCR is specific and sensitive assay. Phenotypically adherent
      strains are divided into two main groups, by use of this multiplex PCR i.e.,
      typical EAEC isolates that carry the three plasmid-borne genes all together and
      atypical EAEC isolates in which the three genes are not linked together.

PMID- 15567142
TI  - HIV-1 intra-subtype superinfection rates: estimates using a structured coalescent
      with recombination.
AB  - Because recombination between a pair of viral genomes can occur only when both
      viruses are present in the same host, genealogical evidence of recombination is
      influenced by the rate of viral migration between infected hosts. If
      superinfection is rare, then recombining viral genomes will usually be more
      closely related to each other than to viral genomes present in other hosts and
      the impact of recombination on the genealogy of a sample of viruses from
      different hosts may be weak. We used this relationship to estimate the relative
      rate of intra-subtype HIV-1 superinfection in six urban populations. Comparisons
      of the population recombination rates estimated from the HIV-1 sequence data with
      population recombination rates estimated for sets of sequences simulated using a
      structured coalescent process suggest that intra-subtype superinfection rates in
      all but one of these populations may be as high as 15% of the corresponding
      infection rate. However, we caution that these estimates might be upwardly biased
      if variation in contact and mixing rates between infected hosts causes viral
      lineages to be concentrated in groups with higher than average superinfection
      rates.

PMID- 15567143
TI  - Applied and fundamental research: towards positive encounters. A position paper.

PMID- 15567144
TI  - Desensitization to gonadotropic hormones: a model system for the regulation of a
      G-protein-coupled receptor with 7-transmembrane spanning regions.
AB  - Gonadotropic hormone, luteinizing hormone, and follicle-stimulating hormone exert
      their effect via activation of G-coupled receptors, which activate the hormone
      sensitive adenylyl cyclase, protein kinase A, and cyclic AMP responsive elements.
      This activation leads to specific de novo synthesis of steroidogenic factors and
      steroidogenic enzymes. In normal cells and following activation of this signaling
      pathway, desensitization period will be followed. This down-regulation, which was
      studied in detail for the last three decays, was found to take place at various
      steps of these signal transduction pathways as well as at different kinetics. A
      common and diverse feature of the mechanism of desensitization in other G-coupled
      7-transmembrane receptor system is also discussed.

PMID- 15567145
TI  - Over-expression of human UREB1 in colorectal cancer: HECT domain of human UREB1
      inhibits the activity of tumor suppressor p53 protein.
AB  - Many fundamental processes, including oncogenesis, have implicated HECT domain
      proteins with ubiquitin ligase activity. The protein human upstream regulatory
      element binding protein 1 (hUREB1) is a HECT domain protein whose function is not
      defined yet. Here, we investigate the function of hUREB1 as a ubiquitin-protein
      ligase in human colorectal cells. Ectopic expression of the HECT domain of hUREB1
      reduces the protein level and transcriptional activity of the p53 tumor
      suppressor, which is abrogated by the deletion in the HECT domain or point
      mutations in the essential residues of the HECT domain. The ubiquitination and
      destabilization of p53 is observed in cells treated with the protease inhibitor
      MG132, implying that the HECT domain of hUREB1 suppresses the transcriptional
      activity of p53 through a ubiquitin-dependent degradation pathway. Based on the
      results of Northern blot analysis, RT-PCR, and immunohistochemical analyses, the
      over-expression of hUREB1 is associated with colorectal carcinoma. Moreover,
      protein levels of hUREB1 and p53 were inversely correlated. These findings
      suggest that hUREB1 can function, at least in part, as a negative regulator of
      p53 during the colorectal carcinoma progression through the ubiquitination
      pathway mediated by the HECT domain.

PMID- 15567146
TI  - Prion disease incubation time is not affected in mice heterozygous for a dynein
      mutation.
AB  - A mechanism for transmission of the infectious prions from the peripheral nerve
      ends to the central nervous system is thought to involve neuronal anterograde and
      retrograde transport systems. Cytoplasmic dynein is the major retrograde
      transport molecular motor whose function is impaired in the Legs at odd angles
      (Loa) mouse due to a point mutation in the cytoplasmic dynein heavy chain
      subunit. Loa is a dominant trait which causes neurodegeneration and progressive
      motor function deficit in the heterozygotes. To investigate the role of
      cytoplasmic dynein in the transmission of prions within neurons, we inoculated
      heterozygous Loa and wild type littermates with mouse-adapted scrapie prions
      intracerebrally and intraperitonially, and determined the incubation period to
      onset of clinical prion disease. Our data indicate that the dynein mutation in
      the heterozygous state does not affect prion disease incubation time or its
      neuropathology in Loa mice.

PMID- 15567147
TI  - Post-transcriptional regulation of CRLR expression during hypoxia.
AB  - Adrenomedullin and CGRP are two potent vasodilator peptides, and their receptors
      are formed by heterodimerization of the CRLR and a RAMP molecule. Hypoxia is
      associated with many diseases of the cardiovascular system. It was recently shown
      that the human CRLR gene promoter contains an HIF-1alpha regulatory element, and
      that CRLR mRNA was increased by hypoxia in human endothelial cells. In the
      present work, we have assessed the effect of hypoxia on CRLR expression both in
      vivo and in vitro using two different experimental models. We have also
      investigated the effect of hypoxia on RAMP expression. (1) We analyzed the
      effects of a chronic hypobaric hypoxia on rat ventricle expression of RAMPs and
      CRLR. (2) Acute hypoxia was studied in human vascular smooth cells from coronary
      artery (CASMC) exposed for 6h to 2% O(2). RT-PCR was used to analyze the mRNA
      expression, and protein levels were determined by Western blotting. A sharp
      increase in HIF-1alpha protein levels was induced by hypoxia in CASMC, and 3.5
      fold rise of the CRLR protein occurred after 1h of hypoxia in face of unchanged
      mRNA levels. The CRLR mRNA levels were only elevated later. A clear decrease of
      the CRLR protein level occurred after 3 and 6h of hypoxia. Thus, acute hypoxia in
      CASMC induced a rapid change of the CRLR protein amount independently of changes
      in the CRLR mRNA. This finding suggested a major post-transcriptional effect of
      hypoxia on CRLR expression in CASMC. RAMP2 and adrenomedullin mRNAs were
      increased after 4h, but no change was observed for RAMP1. Chronic hypoxia in rats
      enhanced both mRNA and protein levels of the three RAMPs and CRLR in right and
      left ventricles. Together, our in vivo and in vitro data suggested that hypoxia
      up-regulates both adrenomedullin and its receptor (CRLR/RAMP2) to enhance the
      signaling at the target cell.

PMID- 15567148
TI  - Study of the preferred modification sites of the quinone methide intermediate
      resulting from the latent trapping device of the activity probes for hydrolases.
AB  - Use of activity probes has been demonstrated to be a powerful tool in modern
      chemical proteomic study. Previously we have designed and synthesized a series of
      mechanism-based activity probes that utilized quinone methide chemistry. Here, we
      characterized the trend of chemical reactivity for the reactive quinone methide
      intermediate 3 (QM-3) resulting from the latent trapping device. In a competition
      assay, the labeling of PTP1B by probe 1a was blocked by externally added cysteine
      without affecting the catalytic activity of the enzyme. Further sequencing
      analysis on the trypsin-digested peptides of probe 1a-labeled PTP1B using tandem
      mass spectrometry revealed that all six cysteine residues of PTP1B are capable of
      being modified by probe 1a. These results indicated that the sulfhydryl group of
      cysteine residue is the preferred nucleophile for the reactive QM-3. Our finding
      provides the first example in understanding the preferred amino acid residues
      modified by the reactive QM-3, which is also the key structural unit responsible
      for forming covalent bonds in many biochemical applications.

PMID- 15567149
TI  - Cloning, expression, and differentiation-dependent regulation of SMAF1 in
      adipogenesis.
AB  - With the aim of identifying novel molecular pathways in the adipocyte, we
      conducted differential screening of DNA filter arrays with probes from 3T3-L1
      preadipocytes and adipocytes, and discovered a novel 0.7kb transcript we term
      small adipocyte factor 1 (SMAF1). SMAF1 encodes a wholly novel 10kDa protein.
      Transfection and localization studies of a SMAF1-EGFP fusion construct indicate
      nuclear localization, suggestive of a possible regulatory role. Northern blot
      analysis of various murine tissues indicates adipose tissue-restricted
      expression, and fractionation of adipose tissue reveals that SMAF1 is expressed
      soley in adipocytes and not in the stromal-vascular cell population. Northern
      blot analysis of brown and white adipogenic conversion reveals that expression of
      SMAF1 closely parallels emergence of an adipocyte phenotype and that TNFalpha
      mediated dedifferentiation of 3T3-L1 adipocytes results in a rapid decline of
      SMAF1 transcript. These data indicate that SMAF1 is closely tied to the adipocyte
      phenotype and predict a novel and possibly regulatory role for this gene in
      adipocyte function.

PMID- 15567150
TI  - Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in
      mice fed high-fat diet.
AB  - The role of inducible nitric oxide synthase (iNOS) in the progression of fibrosis
      during nonalcoholic steatohepatitis remains to be elucidated. This study examined
      the role of iNOS in the progression of fibrosis during steatohepatitis by
      comparing iNOS knockout (iNOS(-/-)) and wild-type (iNOS(+/+)) mice that were fed
      a high-fat diet. Severe fatty metamorphosis developed in the liver of iNOS(+/+)
      and iNOS(-/-) mice. Fibrotic changes were marked in iNOS(-/-) mice. Gelatin
      zymography showed that pro MMP-2 and pro MMP-9 protein expressions were more
      highly induced in iNOS(+/+) mice than in iNOS(-/-) mice. Active forms of MMP-2
      and MMP-9 were clearly present only in the liver tissue of iNOS(+/+) mice. In
      situ zymography showed strong gelatinolytic activities in the liver tissue of
      iNOS(+/+) mice, but only spotty activity in iNOS(-/-)mice. iNOS may attenuate the
      progression of liver fibrosis in steatohepatitis, in part by inducing MMP-2 and
      MMP-9 expression and augmenting their activity.

PMID- 15567151
TI  - 1.42A crystal structure of mini-IGF-1(2): an analysis of the disulfide
      isomerization property and receptor binding property of IGF-1 based on the three
      dimensional structure.
AB  - Insulin and insulin-like growth factor 1 (IGF-1) share a homologous sequence, a
      similar three-dimensional structure and weakly overlapping biological activity,
      but IGF-1 folds into two thermodynamically stable disulfide isomers, while
      insulin folds into one unique stable tertiary structure. This is a very
      interesting phenomenon in which one amino acid sequence encodes two three
      dimensional structures, and its molecular mechanism has remained unclear for a
      long time. In this study, the crystal structure of mini-IGF-1(2), a disulfide
      isomer of an artificial analog of IGF-1, was solved by the SAD/SIRAS method using
      our in-house X-ray source. Evidence was found in the structure showing that the
      intra-A-chain/domain disulfide bond of some molecules was broken; thus, it was
      proposed that disulfide isomerization begins with the breakdown of this disulfide
      bond. Furthermore, based on the structural comparison of IGF-1 and insulin, a new
      assumption was made that in insulin the several hydrogen bonds formed between the
      N-terminal region of the B-chain and the intra-A-chain disulfide region of the A
      chain are the main reason for the stability of the intra-A-chain disulfide bond
      and for the prevention of disulfide isomerization, while Phe B1 and His B5 are
      very important for the formation of these hydrogen bonds. Moreover, the receptor
      binding property of IGF-1 was analyzed in detail based on the structural
      comparison of mini-IGF-1(2), native IGF-1, and small mini-IGF-1.

PMID- 15567152
TI  - Sulfonylurea as well as elevated glucose levels stimulate reactive oxygen species
      production in the pancreatic beta-cell line, MIN6-a role of NAD(P)H oxidase in
      beta-cells.
AB  - Increased oxidative stress may play a key role in the progressive deterioration
      of pancreatic beta-cells and the development of diabetes. However, the underlying
      mechanism is not well understood. Exposure of pancreatic beta-cell line, MIN6
      cells, to elevated glucose level for 2h induced an increase in reactive oxygen
      species (ROS) production, as evaluated by the staining of 2',7'
      dichlorofluorescein diacetate. This effect was completely blocked by NAD(P)H
      oxidase inhibitor (diphenylene iodonium) and protein kinase C (PKC) inhibitor
      (calphostin C), but not affected by other flavoprotein inhibitors (rotenone,
      oxypurinol, or l-N-monomethyl arginine). Glibenclamide also stimulated ROS
      production in a dose-dependent manner. This effect was again blocked by
      diphenylene iodonium and calphostin C. In conclusion, insulin secretagogues, both
      glibenclamide and elevated glucose level, stimulated ROS production in beta-cells
      through a PKC-dependent activation of NAD(P)H oxidase. This mechanism may be a
      novel therapeutic target for preventing the progression of beta-cell
      deterioration.

PMID- 15567153
TI  - Human hepatocytes in mice receiving pre-immune injection with human cord blood
      cells.
AB  - It is well established that certain subpopulations of human adult stem cells can
      generate hepatocyte-like cells when transplanted into adult immunosuppressed
      mice. In the present study, we wanted to explore whether xeno-transplantation of
      human cord blood CD34(+) (hCBCD34(+)) cells during pre-immune stages of
      development in immunocompetent mice might also lead to human-mouse liver
      chimerism. Freshly isolated hCBCD34(+) cells were xeno-transplanted into non
      immunosuppressed mice by both intra-blastocyst and intra-fetal injections. One
      and four weeks after birth, immunostaining for different human-specific
      hepatocyte markers: human hepatocyte-specific antigen, human serum albumin, and
      human alpha-1-antitrypsin indicated the presence of human hepatocyte-like cells
      in the livers of transplanted animals. Detection of human albumin mRNA further
      corroborated the development of pre-immune human-mouse chimeras. The current
      report, besides providing new evidence of the potential of hCBCD34(+) cells to
      generate human hepatocyte-like cells, suggests novel strategies for generating
      immunocompetent mice harboring humanized liver.

PMID- 15567154
TI  - Site-directed mutagenesis alters DnaK-dependent folding process.
AB  - The overproduction of d-aminoacylase (A6-d-ANase) of Alcaligenes xylosoxydans
      subsp. xylosoxydans A-6 (Alcaligenes A-6) is accompanied by aggregation of the
      overproduced protein, and its soluble expression is facilitated by the
      coexpression of DnaK-DnaJ-GrpE (DnaKJE). When the A6-d-ANase gene was expressed
      in the Escherichia coli dnaK mutant dnaK756, little activity was observed in the
      soluble fraction, and it was restored by the coexpression of DnaKJE or the
      substitution of the R354 residue of A6-d-ANase for lysine. These results suggest
      that the guanidino group of the R354 residue of A6-d-ANase disturbs its proper
      folding in the absence of DnaK and the disturbance is eliminated by binding of
      DnaK to the R354 residue in the presence of DnaK. This is the first report that
      the DnaK-dependent folding process of the enzyme is altered by site-directed
      mutagenesis.

PMID- 15567155
TI  - Yin Yang 1 represses alpha-myosin heavy chain gene expression in pathologic
      cardiac hypertrophy.
AB  - In the work presented here, we elucidate a mechanism for the repression of alpha
      myosin heavy chain (MyHC) during pathological cardiac hypertrophy. We demonstrate
      that the transcription factor Yin Yang 1 (YY1) significantly decreases endogenous
      alpha-MyHC mRNA and protein expression in neonatal rat ventricular myocytes.
      Furthermore, mutation of the YY1 binding sites in the proximal rat alpha-MyHC
      promoter increases promoter activity and alleviates YY1-mediated repression of
      the promoter. Despite the presence of 5 sites that bind YY1, only one site,
      located at -94bp of the rat alpha-MyHC promoter, is both necessary and sufficient
      for pathological repression of the promoter by phorbol esters, revealing a unique
      mechanism for the repression of alpha-MyHC expression during cardiac hypertrophy.

PMID- 15567156
TI  - An enzymatic cycling method for the determination of serum total bile acids with
      recombinant 3alpha-hydroxysteroid dehydrogenase.
AB  - A highly sensitive enzymatic cycling method was developed for the serum total
      bile acids assay. We constructed a prokaryotic expression system to prepare the
      recombinant 3alpha-hydroxysteroid dehydrogenase in place of the natural enzyme
      and for the first time used it in the total bile acids assay. The production rate
      of thio-NADH correlated with the bile acids concentration and was measured by the
      change of absorbance at 405/660 nm. The enzymatic cycling method could detect
      0.22 micromol/L total bile acids in serum. Within-run and between-run
      imprecisions were 1.2-3.7% and 2.3-4.8%, respectively. The calibration curve for
      total bile acids in serum was linear between 0.5 and 180 micromol/L. This method
      was free from interference by bilirubin, hemoglobin, ascorbate, and lactate
      dehydrogenase. In conclusion, serum total bile acids could be measured by the
      enzymatic cycling method with recombinant 3alpha-hydroxysteroid dehydrogenase as
      the tool enzyme.

PMID- 15567157
TI  - NO-donating aspirin inhibits the growth of leukemic Jurkat cells and modulates
      beta-catenin expression.
AB  - beta-Catenin has been implicated in leukemic cell proliferation. We compared the
      effects of aspirin (ASA) and the ortho, meta, and para positional isomers of NO
      donating aspirin (NO-ASA) on cell growth and beta-catenin expression in human
      Jurkat T leukemic cells. Cell growth inhibition was strong: IC(50) for p-, o-,
      and m- were 20+/-1.6 (mean+/-SEM), 15+/-1.5, and 200+/-12 microM, respectively,
      in contrast to that of ASA (3200+/-375 microM). The para isomer of NO-ASA
      degraded beta-catenin in a dose- and time-dependent manner coinciding with
      increasing expression of activated caspase-3. The caspase inhibitor ZVAD blocked
      beta-catenin cleavage by p-NO-ASA and partially reversed cell growth inhibition
      by p-NO-ASA but not that by ASA. A denitrated analog of p-NO-ASA did not degrade
      beta-catenin indicating the importance of the NO-donating moiety. Our findings
      suggest that NO-ASA merits further study as an agent against leukemia.

PMID- 15567158
TI  - Characterization of MVP and VPARP assembly into vault ribonucleoprotein
      complexes.
AB  - Vaults are barrel-shaped cytoplasmic ribonucleoprotein particles composed of
      three proteins: the major vault protein (MVP), the vault poly(ADP
      ribose)polymerase (VPARP), and the telomerase-associated protein 1, together with
      one or more small untranslated RNAs. To date, little is known about the process
      of vault assembly or about the stability of vault components. In this study, we
      analyzed the biosynthesis of MVP and VPARP, and their half-lives within the vault
      particle in human ACHN renal carcinoma cells. Using an immunoprecipitation assay,
      we found that it took more than 4h for newly synthesized MVPs to be incorporated
      into vault particles but that biosynthesized VPARPs were completely incorporated
      into vaults within 1.5h. Once incorporated into the vault complex, both MVP and
      VPARP were very stable. Expression of human MVP alone in Escherichia coli
      resulted in the formation of particles that had a distinct vault morphology. The
      C-terminal region of VPARP that lacks poly(ADP-ribose)polymerase activity co
      sedimented with MVP particles. This suggests that the activity of VPARP is not
      essential for interaction with MVP-self-assembled vault-like particles. In
      conclusion, our findings provide an insight into potential mechanisms of
      physiological vault assembly.

PMID- 15567159
TI  - Equilibrium unfolding of an oligomeric protein involves formation of a multimeric
      intermediate state(s).
AB  - Superoxide dismutases (SODs) are important metalloenzymes which protect cells
      against oxidative stress by scavenging reactive superoxides. Missense mutations
      in SODs are known to lead to some familial cases of amyotrophic lateral sclerosis
      and several forms of cancers. In the present study, we investigate the
      guanidinium hydrochloride (GdnHCl)-induced equilibrium unfolding of apo-manganese
      superoxide dismutase (apo-MnSOD) isolated from Vibrio alginolyticus using a
      variety of biophysical techniques. GdnHCl-induced equilibrium unfolding of apo
      MnSOD is non-cooperative and involves the accumulation of stable intermediate
      state(s). Results of 1-anilino-8-naphthalene sulfonate binding experiments
      suggest that the equilibrium intermediate state(s) accumulates maximally in 1.5M
      GdnHCl. The intermediate state(s) appears to be obligatory and occurs both in the
      unfolding and refolding pathways. Size-exclusion chromatography and sedimentation
      velocity data reveal that the equilibrium intermediate state(s) is multimeric. To
      our knowledge, this is the first report of the identification of a multimeric
      intermediate in the unfolding pathway(s) of oligomeric proteins. The formation
      and dissociation of the multimeric intermediate state(s) appears to dictate the
      fate of the protein either to refold to its native conformation or misfold and
      form aggregates as observed in amyotrophic lateral sclerosis.

PMID- 15567160
TI  - Neural precursor cells differentiated from mouse embryonic stem cells relieve
      symptomatic motor behavior in a rat model of Parkinson's disease.
AB  - Pluripotent embryonic stem (ES) cells are the most versatile cells, with the
      potential to differentiate into all types of cell lineages including neural
      precursor cells (NPCs), which can be expanded in large numbers for significant
      periods of time to provide a reliable cell source for transplantation in
      neurodegenerative disorders such as Parkinson's disease (PD). In the present
      study, we used the MESPU35 mouse ES cell line, which expresses enhanced green
      fluorescent protein that enables one to distinguish between transplanted cells
      and cells of host origin. Embryoid bodies (EBs) were formed and were induced to
      NPCs in N2 selection medium plus fibronectin. Praxiology and immunohistochemistry
      methods were used to observe the survival, differentiation, and therapeutic
      effect of NPCs after grafted into the striatum of PD rats. We found that mouse
      ESc were differentiated into nestin-positive NPCs 6 days after the EBs formed and
      cultured in the N2 selection medium. The number of survival NPCs was increased
      significantly by fibronectin. About 23.76+/-2.29% of remaining cells were
      tyrosine hydroxylase (TH)-positive 12 days after NPCs were cultured in N2
      selective medium. The survival rates of NPCs were 2.10+/-0.41% and about 90.90+/
      3.00% of the engrafted NPCs were TH-positive 6 weeks after transplantation into
      the striatum of PD rats. The rotation of PD rats was relieved 3 weeks after the
      NPCs transplantation and this effect was kept for at least 6 weeks. It suggests
      that most of the survival NPCs derived from ES cells differentiated into TH
      positive neurons after grafted into the striatum of PD rats, which produces
      therapeutic effect on PD.

PMID- 15567161
TI  - Molecular mechanism of high altitude respiration: primary structure of a minor
      hemoglobin component from Tufted duck (Aythya fuligula, Anseriformes).
AB  - Avian hemoglobins have attracted much attention in view of the unique oxygen
      transport characteristics. The present study describes the primary structure of
      minor hemoglobin component HbD from Tufted duck (Aythya fuligula), a migratory
      bird seen in Pakistan during the winter season. Separation of the polypeptide
      subunits was achieved by ion exchange chromatography in the presence of 8M urea.
      Molecular masses of the intact protein as well as peptides obtained from chemical
      and enzymatic cleavages were determined by electrospray ionization mass
      spectrometry. The sequence was studied by automatic Edman degradation of the
      native chains and their tryptic/hydrolytic fragments in a gas-phase sequencer.
      Comparison of the hemoglobin sequence with the corresponding sequences of
      Anseriform representatives and other avian species shows residues like alpha(D)23
      Asp, alpha(D)120 Asp as being specific to Tufted duck. The three-dimensional
      structure analyzed with the protein structure modeling package, WHAT IF, using
      the crystal structure coordinates of chicken hemoglobin (PDB code=1hbr) shows
      alpha(D)34 Val, alpha(D)38 Gln, and alpha(D)94 Asp as possible mediators offering
      alternate pathway for oxygen uptake and release thereby leading to distinct
      hypoxia tolerance in the Tufted ducks. Results are discussed with reference to
      function and evolution in the Anseriform representatives.

PMID- 15567162
TI  - RANK-L induces the expression of NFATc1, but not of NFkappaB subunits during
      osteoclast formation.
AB  - We report the program of gene expression during osteoclast formation from
      RAW264.7 cell precursors in response to RANK-ligand (RANK-L) using a combination
      of quantitative real time PCR and Affymetrix gene chip assays. We found that
      genes obligatory to osteoclast formation and function, namely tartrate-resistant
      acid phosphatase, cathepsin K, beta3 integrin, and calcitonin receptors, were up
      regulated by RANK-L markedly by up to approximately 2000-fold. In contrast, we
      found a cluster of genes that were significantly down-regulated: these included
      interleukin-18, insulin-like growth factor-1, interleukin-6 receptor, and
      cathepsins B, C, and L. These results from real time PCR were broadly concordant
      with those obtained from Affymetrix. We also explored the expression of the
      transcription factors of the NFAT and NFkappaB family at days 3 and 5 of culture.
      Whereas NFATc1 expression was increased significantly at days 3 and 5 following
      RANK-L exposure, there were no significant increases in the expression of
      NFkappaB subunits, namely p65, p50, c-Rel, IkappaBalpha, and IkappaBbeta. There
      were also no significant differences in transcription modulator expression
      between days 3 and 5, except for c-Rel and NFATc4, which were both decreased
      significantly at day 5. The studies suggest RANK-L regulates the expression only
      of NFATc1, while it signals through both NFATc1 and NFkappaB.

PMID- 15567163
TI  - The subcellular localization of 3-phosphoinositide-dependent protein kinase is
      controlled by caveolin-1 binding.
AB  - 3-Phosphoinositide-dependent protein kinase 1 (PDK1), a member of the
      serine/threonine kinase family, has been demonstrated to be crucial for cellular
      survival, differentiation, and metabolism. Here, we present evidence that PDK1 is
      associated with caveolin-1, a 22-kDa integral membrane protein, which is the
      principal structural and regulatory component of the caveolae membranes in COS-1.
      First, we noted the presence of two potential caveolin-1 binding motifs
      ((141)FFVKLYFTF(149) and (299)YDFPEKFF(306)) in the PDK1 catalytic domain. Using
      a pull-down approach, we observed that PDK1 interacts physically with caveolin-1
      both in vivo and in vitro. Second, we detected the co-localization of PDK1 and
      caveolin-1 via confocal microscopy. The localization of PDK1 to the plasma
      membrane was disrupted by caveolin binding. Third, in transient transfection
      assays, interaction with caveolin-1 induced a substantial reduction in the in
      vivo serine/threonine phosphorylation of PDK1, whereas the caveolin-1 binding
      site mutant ((141)FFVKLYFTF(149) and (299)YDFPEKFF(306) change to
      (141)AFVKLAFTA(149) and (299)ADAPEFLA(306)) did not. Furthermore, a caveolin-1
      scaffolding peptide (amino acids 82-101) functionally suppressed the self
      phosphorylation and kinase activities of purified recombinant PDK1 protein. Thus,
      our observations indicated that PDK1 binds to caveolin-1 through its caveolin
      binding motifs, and also that the protein-protein interaction between PDK1 and
      caveolin-1 regulates PDK1 self-phosphorylation, kinase activity, and subcellular
      localization.

PMID- 15567164
TI  - S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal
      ligament cells.
AB  - Periodontal ligament (PDL) is a thin fibrous connective tissue located between
      alveolar bone and cementum that remains unmineralized physiologically. It is thus
      thought that PDL cells possess mechanisms to inhibit mineralization. It has been
      demonstrated that S100A4, a member of the S100 calcium-binding protein family, is
      synthesized and secreted by PDL cells, and that it may act as an inhibitor of
      mineralization. However, the mechanisms of action of S100A4 in mineralization
      have not been thoroughly clarified. In the present study we investigated the
      effects of S100A4 inhibition by a short interfering RNA (siRNA) on the expression
      of osteoblast related genes by human PDL cells. Inhibition of S100A4 by siRNA
      resulted in increased expression of osteoblastic markers such as osteopontin and
      osteocalcin, and the osteoblast-specific transcription factors, Runx2/Cbfa1 and
      Osterix. These results indicate that S100A4 suppresses the expression of
      osteoblastic genes in PDL cells and may thus inhibit mineralization in the PDL.

PMID- 15567165
TI  - Divergent effects of estrogen and nicotine on Rho-kinase expression in human
      coronary vascular smooth muscle cells.
AB  - Recent studies have demonstrated that up-regulated Rho-kinase plays an important
      role in the pathogenesis of coronary arteriosclerosis and vasospasm. We have
      shown that inflammatory stimuli, such as angiotensin II and interleukin-1beta, up
      regulate Rho-kinase expression and activity in human coronary vascular smooth
      muscle cells, for which intracellular signal transduction mediated by protein
      kinase C and NF-kappaB is involved. Here, we show that estrogen down-regulates
      while nicotine up-regulates Rho-kinase and that nicotine counteracts the
      inhibitory effect of estrogen on angiotensin II-induced Rho-kinase expression.
      Furthermore, we demonstrated that the intracellular signal transduction of the
      inhibitory effect of estrogen is mediated by an estrogen receptor. These results
      demonstrate that inflammatory stimuli up-regulate Rho-kinase, for which estrogen
      (mediated by an estrogen receptor) and nicotine exert divergent inhibitory and
      stimulatory effects on the Rho-kinase expression, respectively, and may explain
      in part why the incidence of arteriosclerotic and vasospastic disorders is
      increased in postmenopausal women and smokers.

PMID- 15567166
TI  - Circadian gene expression patterns of melanopsin and pinopsin in the chick pineal
      gland.
AB  - The directly light-sensitive chick pineal gland contains at least two
      photopigments. Pinopsin seems to mediate the acute inhibitory effect of light on
      melatonin synthesis, whereas melanopsin may act by phase-shifting the intrapineal
      circadian clock. In the present study we have investigated, by means of
      quantitative RT-PCR, the daily rhythm of photopigment gene expression as
      monitored by mRNA levels. Under a 12-h light/12-h dark cycle, the mRNA levels of
      both pigments were 5-fold higher in the transitional phase from light to dark
      than at night, both in vivo and in vitro. Under constant darkness in vivo and in
      vitro, the peak of pinopsin mRNA levels was attenuated, whereas that of
      melanopsin was not. Thus, whereas the daily rhythm of pinopsin gene expression is
      dually regulated by light plus the intrapineal circadian oscillator, that of
      melanopsin appears to depend solely on the oscillator.

PMID- 15567167
TI  - Estrogen and bisphenol A disrupt spontaneous [Ca(2+)](i) oscillations in mouse
      oocytes.
AB  - The present work aims to study the effects of estrogen or endocrine disrupters
      (EDs) on the dynamic changes in intracellular Ca(2+) concentration of mouse
      immature oocytes (IOs) loaded with Ca(2+)-sensitive dye Fura-2 using an image
      analyzer. The majority of IOs isolated from the ovary exhibited spontaneous
      Ca(2+) oscillations at regular intervals. Entry of external Ca(2+), probably
      through gap junctions, contributes to Ca(2+) oscillations since they were
      reversibly inhibited by removing Ca(2+) from the bathing medium or by the
      application of a gap-junction inhibitor carbenoxolone (CBX, 30 microM). Both
      17beta-estradiol (E2) and E2-BSA, a membrane impermeable estrogen, shortened the
      duration of Ca(2+) oscillations in a dose-dependent manner (1-1000 nM), and
      produced an irregular pattern of the oscillations, strongly suggesting that E2
      acts on the plasma membrane of the oocyte. For bisphenol A (BPA), one of the
      estrogen-mimicking EDs, a 10,000-fold higher concentration (100 microM) was
      necessary to exert similar inhibitory action to that of E2.

PMID- 15567168
TI  - Glutamine is a key regulator for amino acid-controlled cell growth through the
      mTOR signaling pathway in rat intestinal epithelial cells.
AB  - Amino acids, especially branched-chain amino acids such as l-leucine, have been
      shown to regulate activation of p70 S6 kinase and phosphorylation of 4E-BP1
      through the mTOR signaling pathway. In our recent study, l-arginine was also
      shown to activate the mTOR signaling pathway in rat intestinal epithelial cells.
      l-Glutamine is an amino acid that is required for culturing of numerous cell
      types, including rat intestinal epithelial cells. In this study, we showed that l
      glutamine inhibited the activation of p70 S6 kinase and phosphorylation of 4E-BP1
      induced by arginine or leucine in rat intestinal epithelial cells. Although the
      molecular mechanism of l-glutamine-induced inhibition of the mTOR signaling
      pathway is still unknown, the presence of this novel signal pathway may indicate
      that individual amino acids play specific roles for cellular proliferation and
      growth.

PMID- 15567169
TI  - Tissue distribution and hormonal regulation of the breast cancer resistance
      protein (Bcrp/Abcg2) in rats and mice.
AB  - Breast cancer resistance protein (Bcrp/Abcg2) is a member of the ABC transporter
      family. The purpose of this study was to quantify Bcrp mRNA in rat and mouse
      tissues, and to determine whether there are gender differences in Bcrp mRNA
      expression. Rat Bcrp mRNA levels were high in intestine and male kidney, and
      intermediate in testes. Mouse Bcrp expression was highest in kidney, followed by
      liver, ileum, and testes. Male-predominant expression of Bcrp was observed in rat
      kidney and mouse liver. Furthermore, gonadectomy and hypophysectomy experiments
      were conducted to determine whether sex steroids and/or growth hormone are
      responsible for Bcrp gender-divergent expression patterns. Male-predominant
      expression of Bcrp in rat kidney appears to be due to the suppressive effect of
      estradiol, and male-predominant expression of Bcrp in mouse liver appears to be
      due to the inductive effect of testosterone.

PMID- 15567170
TI  - Functional analysis, overexpression, and kinetic characterization of pyruvate
      kinase from Plasmodium falciparum.
AB  - The important role of pyruvate kinase during malarial infection has prompted the
      cloning of a cDNA encoding Plasmodium falciparum pyruvate kinase (pfPyrK), using
      mRNA from intraerythrocytic-stage malaria parasites. The full-length cDNA encodes
      a protein with a computed molecular weight of 55.6 kDa and an isoelectric point
      of 7.5. The purified recombinant pfPyrK is enzymatically active and exists as a
      homotetramer in its active form. The enzyme exhibits hyperbolic kinetics with
      respect to phosphoenolpyruvate and ADP, with K(m) of 0.19 and 0.12 mM,
      respectively. pfPyrK is not affected by fructose-1,6-bisphosphate, a general
      activating factor of pyruvate kinase for most species. Glucose-6-phosphate, an
      activator of the Toxoplasma gondii enzyme, does not affect pfPyrK activity.
      Similar to rabbit pyruvate kinase, pfPyrK is susceptible to inactivation by 1mM
      pyridoxal-5'-phosphate, but to a lesser extent. A screen for inhibitors to pfPyrK
      revealed that it is markedly inhibited by ATP and citrate. Detailed kinetic
      analysis revealed a transition from hyperbolic to sigmoidal kinetics for PEP in
      the presence of citrate, as well as competitive inhibitory behavior for ATP with
      respect to PEP. Citrate exhibits non-competitive inhibition with respect to ADP
      with a K(i) of 0.8mM. In conclusion, P. falciparum expresses an active pyruvate
      kinase during the intraerythrocytic-stage of its developmental cycle that may
      play important metabolic roles during infection.

PMID- 15567171
TI  - alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats.
AB  - Several lines of evidence have suggested that triglyceride accumulation in
      skeletal muscle and pancreatic islets is causally related to type 2 diabetes
      mellitus. We recently showed that alpha-lipoic acid (ALA), a potent antioxidant
      and cofactor of mitochondrial respiratory enzymes, reduces body weight of rodents
      by suppressing food intake and increasing energy expenditure. We sought to
      determine if ALA can prevent the development of diabetes mellitus in obese Otsuka
      Long-Evans Tokushima Fatty (OLETF) rats. Most (78%) untreated OLETF rats showed
      glycosuria at 40 weeks of age, but this was completely prevented by ALA. Compared
      with untreated OLETF rats, ALA reduced body weight and protected pancreatic beta
      cells from destruction. ALA also reduced triglyceride accumulation in skeletal
      muscle and pancreatic islets. These results indicate that ALA prevents diabetes
      mellitus in obese diabetes-prone rats by reducing lipid accumulation in non
      adipose tissue as well as in adipose tissue.

PMID- 15567172
TI  - Induction of a homeodomain-leucine zipper gene by auxin is inhibited by cytokinin
      in Arabidopsis roots.
AB  - Homeobox genes are essential regulators of the development of plants as well as
      other organisms. We chose eight putative Arabidopsis homeobox genes not
      previously characterized and examined their expression in response to treatment
      with auxin/cytokinin. One of them, ATHB53, was further studied because it was
      auxin-inducible and its induction was inhibited by cytokinin. Its full-length
      cDNA was cloned and found to encode a protein of the HD-Zip superfamily. Whole
      mount in situ hybridization and RT-PCR showed that it was expressed in the root
      meristem, and auxin treatment increased its expression, especially in a region
      from 0.3 to 0.6mm from the root tip. These results suggest that ATHB53 plays a
      regulatory role in auxin/cytokinin signaling during root development.

PMID- 15567173
TI  - Xanthorrhizol, a natural sesquiterpenoid from Curcuma xanthorrhiza, has an anti
      metastatic potential in experimental mouse lung metastasis model.
AB  - Xanthorrhizol is a sesquiterpenoid compound isolated from the rhizome of Curcuma
      xanthorrhiza. In this study, the anti-metastatic activity of xanthorrhizol was
      evaluated by using an in vivo mouse lung metastasis model and a tumor mass
      formation assay. Interestingly, xanthorrhizol dramatically inhibited the
      formation of tumor nodules in the lung tissue and the intra-abdominal tumor mass
      formation. Next, to examine the mechanism of the anti-metastatic action of
      xanthorrhizol in the mouse lung metastasis, expression patterns of the several
      intracellular signaling molecules were evaluated using the lung tissues with
      tumor nodules. Higher expression levels of cyclooxygenase-2 (COX-2), matrix
      metalloproteinase-9 (MMP-9), and phosphorylated extracellular signal-regulated
      kinase (ERK) were observed in the metastatic group compared with control, but
      these were attenuated by the treatment of xanthorrhizol. In conclusion,
      xanthorrhizol exerts anti-metastatic activity in vivo and this effect could be
      highly linked to the metastasis-related multiplex signal pathway including ERK,
      COX-2, and MMP-9.

PMID- 15567174
TI  - Loss of annexin A1 expression in human breast cancer detected by multiple high
      throughput analyses.
AB  - To test the efficacy of combined high-throughput analyses (HTA) in target gene
      identification, screening criteria were set using >fivefold difference by
      microarray and statistically significant changes (p<0.01) in SAGE and EST.
      Microarray analysis of two normal and seven breast cancer samples found 129 genes
      with >fivefold changes. Further SAGE and EST analyses of these genes identified
      four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was
      validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1
      in breast cancer was further confirmed at mRNA level by Human Breast Cancer
      Tissue Profiling Array and at protein level by immunohistochemical staining. This
      study demonstrated that combined HTA effectively narrowed the number of genes for
      further study, while retaining the sensitivity in identifying biologically
      important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast
      cancer suggests its involvement in maintaining normal breast biology.

PMID- 15567175
TI  - N-cadherin-mediated cell adhesion determines the plasticity for cell alignment in
      response to mechanical stretch in cultured cardiomyocytes.
AB  - Mechanical stretch has been implicated as the growth stimuli in the heart.
      Physiologically, mechanical stretch is reported to contribute to the orientation
      of cardiomyocytes, though the molecular mechanism remains to be elucidated. This
      study was designed to make clear functional significances of N-cadherin in
      plasticity of cell alignment in response to mechanical stretch. Neonatal rat
      cardiomyocytes, cultured on silicone dishes, were subjected to artificial
      uniaxial cyclic stretch. Mechanical stretch was started at certain times (3-75h)
      after seeding and continued for 24h. Stretch stimulation in 3h after cultivation
      promoted cell orientation running parallel to tension direction. In contrast,
      cardiac myocytes fail to align when exposed to stretch 24-75h after cultivation.
      To address the importance of N-cadherin in the responsiveness to stretch, the
      expression and distribution of N-cadherin were analyzed. Immediately after
      seeding, N-cadherin showed dispersed distributions. During cultivation, N
      cadherin localized to cell-cell contacts accompanied by the upregulation of its
      protein. Next, to investigate influence of cell-cell adhesion, cardiomyocytes
      cultured for 72h were replated by trypsin treatment and exposed to stretch 3h
      after replating. The cardiomyocytes replated by trypsinization were oriented in
      parallel to tension direction by mechanical stretch. Finally, adenoviral
      transfection of dominant-negative N-cadherin recovered the ability to exhibit
      cell orientation in response to stretch. Our results suggested that N-cadherin
      was involved in the oriented responses of cardiomyocytes induced by mechanical
      stretch.

PMID- 15567176
TI  - Genomic organization and expression of 23 new genes from MATalpha locus of
      Cryptococcus neoformans var. gattii.
AB  - The pathogenic yeast Cryptococcus neoformans (Cn) causes cryptococcosis, a life
      threatening disease of the brain. Molecular studies of Cn variety gattii have
      lagged behind other two varieties (var. grubii and var. neoformans) although they
      have distinct biology and disease patterns. We focused on gene discovery in
      MATalpha locus because it predominates in clinical strains. A var. gattii cosmid
      library was screened with DNA probes from other two varieties. Two positive
      clones were sequenced to identify ORFs based on similarities to known proteins,
      and to ESTs using bioinformatics, and manually by a curator. Approximately 76kb
      sequenced DNA revealed 23 genes and ORFs. The existence of predicted genes was
      verified by RT-PCR analyses designed to amplify spliced sequences. The results
      confirmed that the transcripts were expressed both at 30 and 37 degrees C. The
      var. gattii MATalpha locus genes showed rearrangements in order and orientation
      vis-a-vis other two varieties. Mating-specific genes showed higher nonsynonymous
      mutation rates, and gene trees showed var. gattii strains in a distinct clade.
      The identification of the largest number, thus far, of var. gattii structural
      genes should set the stage for future molecular pathogenesis studies.

PMID- 15567177
TI  - The ARF tumor suppressor inhibits BCL6-mediated transcriptional repression.
AB  - The ARF tumor suppressor gene antagonizes generation of various tumors. ARF
      mediated tumor suppression occurs in a p53-independent manner as well as in a p53
      dependent manner. We here demonstrate that BCL6 is a target of the ARF tumor
      suppressor. Either mouse p19(ARF) or human p14(ARF) binds to BCL6 and
      downregulates BCL6-induced transcriptional repression. ARF-mediated
      downregulation of the BCL6 activity may account in part for ARF-mediated tumor
      suppression.

PMID- 15567178
TI  - Mitotic dissociation of IQGAP1 from Rac-bound beta1-integrin is mediated by
      protein phosphatase 2A.
AB  - Assembly of F-actin that links with beta1-integrin during the G1 phase of cell
      cycle is released from beta1-integrin and disrupted at mitosis. However, it
      remains unclear how F-actin assembly to which beta1-integrin anchors is cell
      cycle-dependently regulated. We show that beta1-integrin was co
      immunoprecipitated and co-localized with a small GTPase Rac and its effector
      IQGAP1, along with PP2A-AC, in HME cells during G1. When the cells were
      accumulated to G2/M, the co-immunoprecipitation or co-localization of IQGAP1 and
      PP2A-AC with beta1-integrin was lost, leaving Rac bound to beta1-integrin. The
      dissociated IQGAP1 was co-immunoprecipitated with the concomitantly dissociated
      PP2A-A and -C, indicating the complex formation among the proteins in G2/M cells.
      Falling ball viscometric assays revealed that only IQGAP1-bound beta1-integrin
      Rac in G1 cells exhibited an enhanced F-actin cross-linking activity. The results
      suggest that the mitotic loss of F-actin assembly to which beta1-integrin anchors
      is due to PP2A-mediated dissociation of IQGAP1 from Rac-bound beta1-integrin.

PMID- 15567179
TI  - Recombinant SEC14-like proteins (TAP) possess GTPase activity.
AB  - The three human SEC14-like proteins TAP1, TAP2, and TAP3 were expressed in
      Escherichia coli and purified by means of an amino-terminal His-tag. The
      recombinant TAP proteins bound alpha-, beta-, gamma-, and delta-tocopherol,
      certain phospholipids, and squalene. Intriguingly, the TAP proteins showed
      considerable GTPase activity that was comparable to that of small GTP-binding
      proteins of the Rab family. Although the TAP proteins contain important motifs to
      provide GTPase activity, the surrounding secondary structure markedly differed
      from common G-protein domains. However, these motifs are located in close
      proximity in the TAP structure and may therefore form an active site for GTP
      binding and hydrolysis.

PMID- 15567180
TI  - The relation of breast cancer staging to screening protocol compliance: a
      computer simulation study.
AB  - A computer model based on relational database techniques was used to analyze the
      relationship between staging and population compliance to a breast cancer
      screening protocol. Stage distribution data permitted estimates of compliance to
      the protocol. This relationship followed the equation y=5.83e-2.44x where y was
      compliance and x was disease stage. Application of this equation to SEER and NCDB
      data estimated that the levels of compliance never exceeded 16 percent. Results
      indicated increasing clinical Stage IV disease as population compliance
      decreased. As the clinical staging increased there was increased sub-clinical
      Stage IV disease. With regular screening, simulation suggested that mortality
      would decrease.

PMID- 15567181
TI  - Determining the asymmetry of skin lesion with fuzzy borders.
AB  - It is highly desirable to identify malignant melanoma, a common cancer, at an
      early stage. One important clinical feature of this cancer is asymmetrical skin
      lesions. In this paper, we propose an adaptive fuzzy approach that uses symmetric
      distance (SD) to measure lesions with fuzzy borders. The use of a number of SD
      variations and the adoption of a backpropagation neural network enhances the
      discriminative power of the approach. Digitized images from the Lesion Clinic in
      Vancouver, Canada, demonstrate the accurate classification of asymmetric lesions
      at around 80%.

PMID- 15567182
TI  - Detection of ophthalmic arterial doppler signals with Behcet disease using
      multilayer perceptron neural network.
AB  - Doppler ultrasound is known as a reliable technique, which demonstrates the flow
      characteristics and resistance of ophthalmic arteries. In this study, ophthalmic
      arterial Doppler signals were obtained from 106 subjects, 54 of whom suffered
      from ocular Behcet disease while the rest were healthy subjects. Multilayer
      perceptron neural network (MLPNN) employing delta-bar-delta training algorithm
      was used to detect the presence of ocular Behcet disease. Spectral analysis of
      the ophthalmic arterial Doppler signals was performed by least squares (LS)
      autoregressive (AR) method for determining the MLPNN inputs. The MLPNN was
      trained with training set, cross validated with cross validation set and tested
      with testing set. All these data sets were obtained from ophthalmic arteries of
      healthy subjects and subjects suffering from ocular Behcet disease. Performance
      indicators and statistical measures were used for evaluating the MLPNN. The
      correct classification rate was 96.43% for healthy subjects and 93.75% for
      unhealthy subjects suffering from ocular Behcet disease. The classification
      results showed that the MLPNN employing delta-bar-delta training algorithm was
      effective to detect the ophthalmic arterial Doppler signals with Behcet disease.

PMID- 15567183
TI  - Transcranial electric stimulation of motor pathways: a theoretical analysis.
AB  - The response to transcranial electrical stimulation of the brain is an important
      means of assessing motor pathways in the anesthetized patient. The purposes of
      this study were to elucidate the pattern of axonal excitation produced by
      transcranial stimulation and to demonstrate how this pattern is affected by
      changes in the conductivity or geometry of the skull-CSF-brain complex. To this
      end, analytic solutions to the problem of electrodes placed on a three shell
      spherical model were obtained under constant current conditions. The potentials,
      currents and fields generated were computed and the "activating function" was
      computed for an idealized set of radially organized axons in order to estimate
      the degree of membrane depolarization produced by stimulation. The degree to
      which electromagnetic/radiation effects change these solutions was also
      estimated. The pattern of stimulation was only slightly dependent on the
      conductivity and the thickness of the CSF layer. Axons very close to the anode
      were stimulated with lowest threshold at the brain surface. Axons further away
      were stimulated with higher thresholds and the point of maximum stimulation moved
      nearer the center of the sphere. Near the cathode, stimulation was maximal about
      5-7 degrees away from the edge of the electrode but the peak magnitude of the
      activating function was generally 20 times lower than over the anode.

PMID- 15567184
TI  - On a relaxation-labelling algorithm for quantitative assessment of tumour
      vasculature in tissue section images.
AB  - Although tumour vasculature constitutes a biological factor playing a crucial
      role in the radiation response of tumours, the current procedures of assessment
      are semiquantitative, typically employing visual examination of stained
      histological material. Such techniques are also time consuming, and inefficient
      of extracting essential information on the vascular network. Image analysis has
      yet to contribute significantly in this direction, and most studies to date focus
      on blood vessel segmentation through empirical, user-selected thresholds. The
      present paper proposes an alternative segmentation approach, based on a
      probabilistic relaxation algorithm, applied in microscopic images of stained
      tissues. After image partitioning various information is obtained, such as
      vascular domains and geometrical characteristics of vessels.

PMID- 15567185
TI  - On exact string matching of unique oligonucleotides.
AB  - Unique, gene-specific oligonucleotides are used for many genetic investigations
      such as polymerase chain reaction, gene cloning, microarray technology and
      antisense DNA studies. It is a computationally demanding task to extract these
      oligonucleotides from DNA databases. We studied the problem from the point of
      view of the string matching problem. We implemented and tested several exact
      string matching algorithms and modified the implementations to be as effective as
      possible. Ten different implementations were tested on yeast genomic sequence
      data. The run times for the best algorithms were significantly improved compared
      to conventional approaches, while in principle, i.e. in respect of theoretical
      time complexity, these algorithms do not actually differ essentially from each
      other.

PMID- 15567186
TI  - Agonist-specific regulation of the delta-opioid receptor.
AB  - Delta opioid receptor (DOR) agonists are attractive potential analgesics, since
      these compounds exhibit strong antinociceptive activity with relatively few side
      effects. In the past decade, several novel classes of delta-opioid agonists have
      been synthesized. Recent experimental data indicate that structurally distinct
      opioid agonists interact differently with the delta-opioid receptor.
      Consequently, individual agonist-bound DOR conformations may interact differently
      with intracellular proteins. In the present paper, after a brief review of the
      cellular processes that contribute to homologous desensitization of the DOR
      signaling, we shall focus on experimental data demonstrating that chemically
      different agonists differ in their ability to phosphorylate, internalize, and/or
      down-regulate the DOR. Homologous regulation of the opioid receptor signaling is
      thought to play an important role in the development of opioid tolerance.
      Therefore, agonist-specific differences in DOR regulation suggest that by further
      chemical modification, delta-selective opioid analgesics can be designed that
      exhibit a reduced propensity for analgesic tolerance.

PMID- 15567187
TI  - Effects of nanomolar concentration dihydroouabain on calcium current and
      intracellular calcium in guinea pig ventricular myocytes.
AB  - The effects of nanomolar concentration of dihydroouabain (DHO) on L-type calcium
      current (ICa-L), TTX-sensitive calcium current (ICa(TTX)), and intracellular
      calcium concentration ([Ca2+]i) were investigated in guinea pig ventricular
      myocytes. The whole-cell patch-clamp technique was used to record ICa-L and
      ICa(TTX); [Ca2+]i was detected and recorded with the confocal microscopy. The
      nanomolar concentration of DHO increased the ICa-L, ICa(TTX), and [Ca2+]i, which
      could be partially inhibited by nisoldipine or TTX, but still appeared in the
      absence of extracellular K+ and Na+. These data suggest that DHO could increase
      [Ca2+]i in non-beating myocytes via stimulating the ICa-L and ICa(TTX), or
      perhaps triggering directly a release of intracellular calcium.

PMID- 15567188
TI  - Effects of gold on testicular steroidogenic and gametogenic functions in immature
      male albino rats.
AB  - The present study was undertaken to evaluate the effects of gold chloride, a
      metallic earth salt, on steroidogenic and gametogenic functions of testis in
      immature rats. Immature rats of Wistar strain, were injected (s.c.) with gold
      chloride at the dose of 0.3 mg and 0.5 mg/kg body weight/day for 26 days. All the
      treated animals along with the vehicle-treated controls were sacrificed 24 hours
      after last injections. Testicular steroidogenic activity was evaluated by
      measuring the activities of two steroidogenic key enzymes, Delta5-3beta
      hydroxysteroid dehydrogenase (Delta5-3beta-HSD) and 17-beta hydroxysteroid
      dehydrogenase (17-beta HSD). Gametogenic capacity was determined by counting the
      number of germ cells at stage VII of seminiferous cycle. Plasma levels of
      testosterone (T) was measured by radioimmunoassay (RIA). Administration of gold
      chloride at a dose of 0.3 mg/ kg body weight for 26 days led to insignificant
      changes of testicular Delta5-3beta-HSD,17beta-HSD activities and gametogenesis
      along with plasma T. In contrast 0.5 mg gold chloride treatment for 26 days
      caused a significant increase in plasma T (p < 0.001) along with stimulation of
      testicular Delta5-3beta-HSD activity (p < 0.001) and 17beta-HSD activity (p <
      0.001). Gametogenic activity exhibited a significant increase in the number of
      step 7 spermatids (7Sd) (p < 0.001) at stage VII of seminiferous cycle when
      compared to control. The results of our experiment suggest that gold chloride
      treatment might be associated with significant stimulatory effects on testicular
      activities. Furthermore, since hormonal changes, altered steroidogenic enzymes
      and gametogenic activities were evident to a specific dose of gold chloride
      treatment, our data may have some clinical implication on the stimulation of
      fertility.

PMID- 15567189
TI  - Whole blood serotonin and platelet activation in depressed post-myocardial
      infarction patients.
AB  - Depression is an independent risk factor for post myocardial infarction (MI)
      mortality. Abnormalities in platelet function have been proposed as one of the
      mechanisms involved in increased cardiovascular risk among patients with
      depression post-MI. Depression in somatically healthy patients has been
      associated with increased platelet activation. Some but not all studies showed
      changes in blood serotonin level. Increased platelet activation and blood
      serotonin level have been associated with increased risk of cardiac events in
      patients with MI. The goal of this study was to investigate whether 1) depressed
      post-MI patients have higher markers of platelet activation as measured by plasma
      levels of beta-thromboglobulin (betaTG), platelet factor 4 (PF4) and soluble CD40
      ligand (sCD40L) and higher serotonin (5-HT) levels than non-depressed post-MI
      patients and 2) treatment with the antidepressant mirtazapine decreases platelet
      activation. In this study, 25 depressed post-MI patients were asked for blood
      collection before start as well as after 8 weeks treatment with mirtazapine or
      placebo. The control group (n=22) consisted of non-depressed post-MI patients,
      matched for age, gender and time elapsed since MI. Plasma levels of betaTG, PF4
      and sCD40L were not statistically different between the groups, but 5-HT levels
      were significantly higher in depressed patients. Treatment with mirtazapine
      resulted in a non-significant decrease in betaTG and PF4 and platelet 5-HT
      levels. Platelet and whole blood 5-HT, but not platelet activation was
      significantly increased in depressed post-MI patients. Treatment with mirtazapine
      showed a non-significant decrease in platelet activation and platelet 5-HT.

PMID- 15567190
TI  - Effect of desflurane-induced preconditioning following ischemia-reperfusion on
      nitric oxide release in rabbits.
AB  - Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial
      infarction. Desflurane produces anesthetic preconditioning to protect the
      myocardium against infarction. In the model of myocardial ischemia-reperfusion
      injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and
      studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white
      rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed
      by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long
      lasting left anterior descending coronary artery (LAD) occlusion and three hours
      (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly
      allocated into four groups for preconditioning treatment (eight for each group).
      The control group did not receive any preconditioning treatment. The desflurane
      group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar
      concentration) for 30 min that was followed by a 15 min washout period. The L
      NAME-desflurane group received L-NAME (NG-nitro-L-arginine methyl ester; non
      selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0
      MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV.
      Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH),
      creatine kinase (CK) activity and myocardial perfusion were recorded
      simultaneously. We have found that hemodynamic values of the coronary blood flow
      before, during, and after LAD occlusion were not significantly different among
      these four groups. For the myocardial ischemia-reperfusion injury animals, the
      infarction size (mean +/- SEM) in the desflurane group was significantly reduced
      to 18 +/- 3% in the area at risk as compared with 42 +/- 7% in the control group,
      35 +/- 6 in the L-NAME group, and 34 +/- 4% in the L-NAME-desflurane group. The
      plasma LDH, CK levels, and duration of ventricular arrhythmia were also
      significantly decreased in the desflurane group during ischemia-reperfusion
      injury. Our results indicate that desflurane is an anesthetic preconditioning
      agent, which could protect the myocardium against the ischemia-reperfusion
      injury. This beneficial effect of desflurane on the ischemic preconditioning is
      probably through NO release since L-NAME abrogates the desflurane preconditioning
      effect.

PMID- 15567191
TI  - Preservation of neurological functions by nitric oxide synthase inhibitors in
      conscious rats following delayed hemorrhagic shock.
AB  - Excessive production of nitric oxide (NO) as result of inducible nitric oxide
      synthase (iNOS) induction has been implicated in the pathophysiology of
      hemorrhagic shock. Our aim was to study the effects of NOS inhibitors,
      aminoguanidine (AG) and NG-nitro-L-arginine methyl ester (L-NAME), on survival
      rate, mean arterial blood pressure (MABP), temporal evolution of infarct volume,
      nitric oxide (NO) production and neurological deficit in a model of delayed
      hemorrhagic shock (DHS) in conscious rats. Our results showed that the NOS
      inhibitors significantly improved survival rate, MABP, and attenuated brain NO
      overproduction 24, 48 h and 72 h after DHS. AG reduced brain infarct volume and
      improved the neurological performance evaluated by the rotameric and grip
      strength tests while L-NAME did not show protective effect in rats following DHS.
      These findings suggest that NO formation via iNOS activation may contribute to
      organ damage and that the selective iNOS inhibitor, AG, may be of interest as a
      therapeutic agent for neurological recovery following DHS.

PMID- 15567192
TI  - Constituents in Easter lily flowers with medicinal activity.
AB  - Easter lily (Lilium longiflorum) flowers have been used in traditional medicine
      for alleviating many ailments. However, the chemical basis of its bioactivity has
      not been investigated. We have determined bioactive components in Easter lily
      flowers using lipid peroxidation and cyclooxygenase enzyme inhibitory assays and
      found to be kaempferol (1), kaempferol glycosides (2, 3, 4, 8, 9 and 10),
      quercetin glycosides (5, 6 and 7), a regaloside (11), a chalcone (12) and a fatty
      acid fraction (13). The structures of compounds were determined by NMR, IR,
      UV/VIS and mass spectroscopic studies. Compound 1 showed the highest COX-1
      inhibition (94.1%) followed by 3, 8 and 12 with 38.7, 30.8 and 32.4%,
      respectively. Only compound 1 inhibited COX-2 enzyme by 36.9% at 80 ppm. In lipid
      peroxidation inhibitory assay, kaempferol showed 37 and 100 % inhibitions at 1
      and 10 ppm, respectively. At 10 ppm, more than 20% inhibition was observed for
      compounds 4, 7, 10, 11 and 12 and 53% for compound 3. The compounds reported in
      here are isolated for the first time from Easter lily flowers including novel
      compounds 10, 11 and 12. Our results suggest that kaempferol and quercetin
      flavonoids contributed to the anecdotal medicinal properties of Easter lily
      flowers.

PMID- 15567193
TI  - Benznidazole, a drug used in Chagas' disease, ameliorates LPS-induced
      inflammatory response in mice.
AB  - Benznidazole (BZL) is a drug currently used for treating Chagas' disease. Given
      our earlier demonstration in which BZL downregulated cytokine and nitric oxide
      (NO) synthesis by LPS and/or IFN-gamma-stimulated murine macrophages, we have now
      analysed whether this compound could exert beneficial effects in a model of LPS
      induced inflammation in C57BL/6 mice. The lethal model consisted of two LPS
      intraperitoneal injections, 200 microg each separated by 2 h, with BZL given
      orally at a dose of 200 mg/kg, 18 and 2 h before the first challenge and 20 and
      44 hr following the second one. In this model, BZL treatment led to a
      significantly decreased mortality in comparison with untreated counterparts.
      Remaining experiments were carried out in mice given a unique LPS dose,
      pretreated with BZL or not, since those subjected to the lethal protocol were
      unsuitable for laboratory handling. Analysis of IL-1beta, IL-6, TNF-alpha, IL-12
      and iNOS mRNA expression in liver samples taken at 90 min post-LPS showed a
      marked reduction of the two latter mRNAs in BZL-treated mice. These animals also
      displayed significantly decreased peaks levels of serum TNF-alpha and IL-6,
      accompanied by a diminished number of IL-6-producing peritoneal macrophages.
      Present effects may broaden the potential usefulness of BZL in situations
      accompanied by an excessive inflammatory response.

PMID- 15567194
TI  - Induction of cytochrome P4501A (CYP1A) by clotrimazole, a non-planar aromatic
      compound. Computational studies on structural features of clotrimazole and
      related imidazole derivatives.
AB  - The classical pathway for induction of cytochrome P4501A (CYP1A) by xenobiotics
      is ligand binding to the aryl hydrocarbon receptor (AhR). High-affinity AhR
      ligands are planar polyaromatic molecules such as the prototypic ligand, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). The present work investigated the ability of
      the imidazole derivative, clotrimazole [1-(2'chlorotrityl)imidazole, CLO], to
      induce CYP1A in cultured rainbow trout (Oncorhynchus mykiss) hepatocytes at the
      catalytic activity (determined as 7-ethoxyresorufin-O-deethylase, EROD) and at
      the transcriptional level. CLO resulted in a significant increase of hepatocyte
      EROD activity and CYP1A mRNA at a concentration of 1.56 microM. Computational
      studies on the molecular structure of CLO show that CLO is unlikely to take a
      planar conformation. Further indications that CLO does not behave like a planar
      AhR ligand come from the experimental observation that co-incubation of trout
      hepatocytes with CLO and the AhR antagonist, alpha-naphthoflavone (alpha-NF), did
      not result in an inhibition of CLO induction of CYP1A mRNA, whereas alpha-NF was
      able to inhibit CYP1A induction by the prototpyic, planar AhR ligand, beta
      naphthoflavone. The experimental findings on CLO agree with previous results
      obtained for another non-planar imidazole derivative, 1-benzylimidazole (BIM).
      Further, computational studies showed that the non-planar imidazoles, BIM and
      CLO, are highly similar with respect to some electrostatic properties, namely the
      dipole moment and the molecular electrostatic potential (MEP). Overall our
      experimental and computational studies suggest that transcriptional activation of
      CYP1A by the imidazole derivatives CLO and BIM is mediated by a mechanism
      different to that of prototypic CYP1A inducers such as the planar AhR-ligands.

PMID- 15567195
TI  - Humidity and aggregate content correction factors for air-coupled ultrasonic
      evaluation of concrete.
AB  - This paper describes the use of non-contact ultrasound for the evaluation of
      concrete. Micromachined capacitance transducers are used to transmit ultrasonic
      longitudinal chirp signals through concrete samples using air as the coupling
      medium, and a pulse compression technique is then employed for measurement of
      time of flight through the sample. The effect on the ultrasonic wave speed of
      storing concrete samples, made with the same water/cement ratio, at different
      humidity levels is investigated. It is shown that there is a correlation between
      humidity and speed of sound, allowing a correction factor for humidity to be
      derived. A strong positive linear correlation between aggregate content and speed
      of sound was then observed; there was no obvious correlation between compressive
      strength and speed of sound. The results from the non-contact system are compared
      with that from a contact system, and conclusions drawn concerning coupling of
      energy into the samples.

PMID- 15567196
TI  - Estimating organic chain length through sound velocity measurements.
AB  - The ability to measure the length of polymers while monitoring their production
      is evidently extremely valuable, but is also a useful tool for chemical
      identification purposes at other times, e.g. the analysis of waste water. A study
      of the relationship between velocity of sound and chain length has been carried
      out. Initial studies were performed on two model systems; a series of pure liquid
      n-alkanes (pentane to hexadecane) and 1-alcohols (methanol to 1-dodecanol). This
      study was extended to look at an industrially significant system of
      dimethylsiloxanes 200 fluid (L2, 0.65 cSt) to 200 fluid (5000 cSt). Corresponding
      density data have been taken from the literature and the adiabatic
      compressibility determined. The measured adiabatic compressibility has been
      compared with two molecular models of wound velocity, the Schaaffs model and a
      development of the Urick equation. The Urick equation approach is based on a
      determination of the compressibility of the methylene or siloxane repeat units
      which make up the chains in these linear molecules. We show that the Urick
      equation approach accurately predicts sound velocity and compressibility for the
      higher members of each series, whilst the Schaaffs approach fails for the 1
      alcohols. We suggest that this is because of the influence of the hydroxyl end
      group through hydrogen bonding with methylene groups within the chain. This
      interaction modifies the derived compressibility of the methylene groups, so
      reducing their compressibility relative to that of the n-alkanes. The technique
      described provides valuable new insights into end-group, intermolecular and intra
      molecular interactions in liquid linear-chain molecules. From this detailed
      analysis of the mechanisms involved, a model is derived. This model can give very
      precise estimations of the composition of a pure liquid. In the case of mixtures
      of polymers, it is necessary to use the modified Urick equation and then, in
      addition, the concentration dependence of both the velocity of sound and the
      density must be measured.

PMID- 15567197
TI  - A study on the primary and secondary nucleation of ice by power ultrasound.
AB  - Several different investigations have been carried out to study the primary and
      secondary nucleation of ice by sonocrystallisation. Firstly, the primary
      nucleation of discrete ice crystals in a supercooled sucrose solution has been
      observed. For increasing concentrations of sucrose solutions from 0 to 45 wt%,
      the nucleation temperature consistently occurs at a higher nucleation temperature
      in the presence of ultrasound. The nucleation temperature also increases as the
      power output and duty cycle of a commercial ultrasonic horn are increased. Snap
      shot images of the bubble clouds obtained from the ultrasonic horn also show that
      the number of bubbles appears to increase as the ultrasonic output is increased.
      This suggests that the nucleation of ice is related to the power output and
      number of cavitation bubbles. The effect of a single bubble on the
      sonocrystallisation of ice is discussed. High-speed movies (1120 fps) have shown
      that the crystallisation appears to occur in the immediate vicinity of the single
      bubble. In most cases, many crystals are observed and it is not known whether a
      single ice crystal is being fragmented by the bubble or whether many crystals are
      being initiated. The bubble appears to undergo a dancing regime, frequently
      splitting and rejoining and also emitting some small microbubbles. A study on the
      secondary nucleation of ice in sucrose solutions has been carried out using a
      unique ultrasonic cold stage device. Images taken using a microscope system show
      that the pre-existing ice dendrite crystals can be broken up into smaller
      fragments by an ultrasonic field. Cavitation bubbles appear to be important
      during the fragmentation process, possibly melting any ice crystals in their
      path. Flow patterns around cavitation bubbles have also been observed, and these
      may be responsible for the fragmentation of ice crystals.

PMID- 15567198
TI  - Detection and quantification of insoluble particles by ultrasound spectroscopy.
AB  - The Ultrafood system, a custom-built diagnostic ultrasound device, is used to
      accurately measure the concentration of particulate matter in a fluctuating high
      temperature liquid system. The two main problems, of thermal expansion and
      thermal variation in ultrasonic outputs were tackled by multi-distance
      measurement and low frequency spectroscopy, respectively. The resulting
      techniques have application at laboratory, scale for investigation of particulate
      suspensions and for online process monitoring.

PMID- 15567199
TI  - Ultrasonic techniques for nondestructive testing of standing trees.
AB  - The aim of this study is to assess wood quality of standing trees with ultrasonic
      velocity methods. The ultrasonic techniques currently used are: scattering based
      techniques that use travel time and other wave parameters for measuring the
      elastic constants of wood, and ultrasonic tomographic imaging techniques which
      seek to provide a high resolution picture of the defect. Scattering based
      techniques were firstly used as nondestructive techniques with increment cores of
      5 mm diameter. On these specimens measurements with bulk waves--longitudinal and
      shear were used to detect the influence of sylvicultural treatment (pruning) on
      wood quality and also to detect defects (slope of grain, wavy figures). High
      resolution imaging techniques were developed for imaging abnormalities induced by
      biological attacks of fungi or insects in standing trees. In this case,
      ultrasonic tomography refers to cross-sectional imaging of trees from data
      collected by illuminating the tree from different directions. Ultrasonic images
      were reconstructed from the time of flight. The images were reconstructed from
      120 measurements in situ and through the bark with direct transmission technique,
      using 1 MHz transducers. The resolution is 5 cm.

PMID- 15567200
TI  - Acoustically assisted removal of nitrogen oxide from high temperature flue gas.
AB  - The present study focuses on a possibility for improving NO removal efficiency
      from flue gas by application of powerful sound waves. The sound waves (frequency
      6.9-17.2kHz, intensity 144-160dB) are propagated from Hartmann sound generators
      to a preheated graphite disk inside a vertical reaction tube (height 1.8m, I.D.
      105mm). An Ar-NO synthetic mixture (NO 911-934ppm) is blown onto the disk surface
      to perform reactions in the system C-NO. It is found that the NO reduction rate
      can be significantly enhanced by the sound waves but the enhancement effect is
      dependent on the sound frequency, intensity and temperature of disk surface. The
      better effects are obtained at a temperature of 973K and sound frequencies
      between 9.6 and 12.4kHz. Under these conditions, the sound application results in
      3-5-fold enhancement of NO reduction rate. The obtained effects are explained in
      terms of gas-phase mass transfer controlling mechanism and of near surface
      turbulent diffusivity.

PMID- 15567201
TI  - Ultrasonic velocity in water-ethanol-sucrose mixtures during alcoholic
      fermentation.
AB  - During alcoholic fermentation, sucrose and water are transformed into ethanol and
      carbon dioxide by the action of yeast enzymes. The measurement of the velocity of
      an ultrasonic pulse travelling through a fermentation tank can be used to
      characterize the state of the process. In this work, an experimental study of the
      density and ultrasonic velocity in the ternary mixture (water-ethanol-saccharose)
      is presented. Experimental results were compared to ideal density and to commonly
      used expressions of the sound velocity in liquid mixtures (Urick, Natta
      Baccaredda and Nomoto). A semiempirical approach was proposed to improve the
      efficiency of theoretical models when dealing with mixtures of associated
      liquids.

PMID- 15567202
TI  - Sensitivity analysis of an inverse procedure for determination of elastic
      coefficients for strong anisotropy.
AB  - The elastic coefficients of anisotropic solids are often evaluated from
      measurements of phase or group velocities of ultrasonic bulk waves by the usage
      of inverse optimizing procedures. This paper discusses the effects of various
      factors on such procedures results for transversely isotropic solids with
      considerably strong anisotropy. First, the inverse determination of all elastic
      coefficients of unidirectional CFRP composite is briefly outlined. Then the
      results of the optimization are treated as exact values and the sensitivity of
      the optimizing process versus main considered sources of inaccuracies is
      analyzed. Results of extensive simulations are presented to illustrate the effect
      of input data distortion, input data incompleteness, and geometrical conversion
      from experimentally obtained group velocities into corresponding phase velocities
      used as input data for the optimizing procedure. The paper takes note of how
      information about the elastic coefficients can be extracted from the different
      segments of the phase velocity surface. The stability versus input data
      distortion for inversion from group velocities and phase velocities is compared
      and the importance of reliable geometrical converting from group into phase
      velocities is illustrated. An novel method for geometrical conversion of
      distorted group velocity data into corresponding phase velocities based on affine
      combinations of low-order polynomials is presented and compared with piecewise or
      high-order polynomial fitting.

PMID- 15567203
TI  - Intra-operative acoustic hemostasis of liver: production of a homogenate for
      effective treatment.
AB  - OBJECTIVE: We have shown that High-Intensity Focused Ultrasound (HIFU) can
      effectively control bleeding from injuries to solid organs such as liver, spleen,
      and lung. Achievement of hemostasis was augmented when a homogenate of tissue and
      blood was formed. The objective of this study was to investigate quantitatively
      the effect of homogenate production on HIFU application time for hemostasis.
      Possible mechanisms involved in homogenate production were also studied. METHODS:
      Ten anesthetized rabbits had laparotomy and liver exposure. Liver incisions, 15
      25 mm long and 3-4 mm deep, were made followed immediately by HIFU application.
      Two electrical powers of 80 and 100 W corresponding to focal acoustic intensities
      of 2264 and 2829 W/cm(2), respectively were used. Tissue and homogenate
      temperatures were measured. Smear and histological tissue sample analysis using
      light microscopy were performed. RESULTS: In treatments with homogenate
      formation, hemostasis was achieved in 76+/-1.3 s (Mean+/-Standard Error Mean:
      SEM) at 80 W. In treatments without homogenate formation (at 80 W), hemostasis
      was achieved in 106+/-0.87 s. At 100 W, hemostasis was achieved in 46+/-0.3 s.
      The time required for homogenate formation, at 80 and 100 W were 60+/-2.5 and
      23+/-0.3 s, respectively. The homogenate temperature was 83 degrees C (SEM 0.6
      degrees C), and the non-homogenate tissue temperature at the treatment site was
      60 degrees C (SEM 0.4 degrees C). The smear and histological analysis showed
      significant blood components and cellular debris in the homogenate, with some
      intact cells. CONCLUSION: The HIFU-induced homogenate of blood and tissue
      resulted in a statistically significant shorter HIFU application time for
      hemostasis. The incisions with homogenate had higher temperatures as compared to
      incisions without homogenate. Further studies of the correlation between
      homogenate formation and temperature must be done, as well as studies on the long
      term effects of homogenate in achieving hemostasis.

PMID- 15567204
TI  - Frequency dependence of the acoustic radiation force acting on absorbing
      cylindrical shells.
AB  - The frequency dependence of the radiation force function Y(p) for absorbing
      cylindrical shells suspended in an inviscid fluid in a plane incident sound field
      is analysed, in relation to the thickness and the content of their interior
      hollow region. The theory is modified to include the effect of hysteresis type
      absorption of compressional and shear waves in the material. The results of
      numerical calculations are presented for two viscoelastic (lucite and phenolic
      polymer) materials, with the hollow region filled with water or air indicating
      how damping and change of the interior fluid inside the shell's hollow region
      affect the acoustic radiation force. The acoustic radiation force acting on
      cylindrical lucite shells immersed in a high density fluid (in this case mercury)
      and filled with water in their hollow region, is also studied.

PMID- 15567205
TI  - A useful analytical description of the coefficients in an inhomogeneous wave
      decomposition of a symmetrical bounded beam.
AB  - If a bounded beam is described using a superposition of infinite inhomogeneous
      waves, the values of the coefficients attributed to each inhomogeneous wave are
      found using a classical optimization procedure, whence it is impossible to
      describe the obtained values analytically. In this paper, we develop a new and
      easy to apply straightforward analytical method to find the appropriate values of
      the sought coefficients. Supplementary to its analytical and straightforward
      nature, the method proves to reduce the inherent instabilities found in the
      inhomogeneous wave decomposition.

PMID- 15567206
TI  - On low order moments of the homodyned-K distribution.
AB  - Fractional low order moments have been reported as beneficial for sampling
      computations using the K distribution. However, it has been recently pointed out
      that this it not the case for the homodyned-K distribution for a tissue
      discrimination problem. In this paper we show that such an statement is not fully
      justified. To that end, we follow a standard pattern recognition procedure both
      to determine class separability measures and to classify data with several
      classifiers. We conclude that the optimum order of the moments is intimately
      linked to the specific statistical properties of the tissues to be discriminated.
      Some ideas on how to choose the optimum order are discussed.

PMID- 15567207
TI  - Clinical features of depressed outpatients with and without co-occurring general
      medical conditions in STAR*D.
AB  - BACKGROUND: A significant percentage of patients with major depressive disorder
      (MDD) suffer from concurrent general medical conditions (GMCs). OBJECTIVE: The
      objective of this preliminary report was to describe the rates of co-occurring
      significant GMCs and the clinical correlates and symptom features associated with
      the presence of GMCs. DESIGN: Baseline cross-sectional case-control study of
      patients enrolling in a prospective randomized multistage treatment study of MDD.
      SETTING: Fourteen regional U.S. centers representing 19 primary care and 22
      psychiatric practices. PATIENTS: One thousand five hundred outpatients with DSM
      IV nonpsychotic MDD. MEASUREMENTS: Sociodemographic status, medical illness
      ratings, psychiatric status, quality of life and DSM-IV depression symptom
      ratings. RESULTS: The prevalence of significant medical comorbidity in this
      population was 52.8% (95% CI 50.3-55.3%). Concurrent significant medical
      comorbidity was associated with older age, lower income, unemployment, limited
      education, longer duration of index depressive episode and absence of self
      reported family history of depression. Somatic symptoms common in MDD were
      endorsed at a higher rate in those with GMCs. Those without a GMC had higher
      rates of endorsement of impaired mood reactivity, distinct mood quality and
      interpersonal sensitivity. CONCLUSIONS: Concurrent GMCs are common among
      outpatients with MDD in both primary care and specialty settings. Concurrent GMCs
      appear to influence the severity and symptom patterns in MDD and describe a
      vulnerable population with sociodemographic challenges to effective assessment
      and treatment.

PMID- 15567208
TI  - Depression and diabetes symptom burden.
AB  - OBJECTIVE: To examine the relationship among patient-reported diabetes symptoms,
      severity of depressive illness and objective measures of diabetes control and
      severity among a population-based sample of patients with diabetes. METHODS: A
      mailed survey was sent to all patients with diabetes from nine primary care
      clinics of a Health Maintenance Organization. The Patient Health Questionnaire
      (PHQ-9) was used to diagnose major depression, the Self-Completion Patient
      Outcome instrument assessed diabetes symptoms and automated medical record data
      were used to measure diabetes treatment intensity, HbA(1c) levels, diabetes
      complications and medical comorbidity. Analysis of covariance (ANCOVA) was used
      to determine if the number of diabetes symptoms was related to having major
      depression and to number of depressive symptoms. Logistic regression analyses
      determined the relative strengths of the associations between each individual
      diabetic symptom and presence of major depression, HbA(1c) levels above 8.0% and
      two or more diabetes complications. RESULTS: Among 4168 patients with diabetes,
      those with major depression (N=487) reported significantly more diabetes symptoms
      (mean=4.40) than participants without depression (mean=2.46) after adjusting for
      demographic characteristics, objective measures of diabetes severity and medical
      comorbidity [F(1,4029)=339.31, P<.0001]. The overall number of diabetes symptoms
      was related to the number of depressive symptoms (from 0 to 9) endorsed by
      participants [F(9,4021)=110.05, P<.0001]. Logistic regression analyses found that
      depression was significantly related to each of the 10 diabetes symptoms (all
      P<.001). CONCLUSIONS: The depression-diabetes symptom association is stronger
      than the association of diabetes symptoms with measures of glycemic control and
      diabetes complications.

PMID- 15567209
TI  - Use of the Beck Depression Inventory-II with African American primary care
      patients.
AB  - The Beck Depression Inventory-II (BDI-II) is one of the most common self-report
      instruments used for depression screening. However, there is a lack of research
      examining the effectiveness of this instrument in detecting depression in an
      African American primary care sample. The current study included 220 African
      American primary care patients who completed the BDI-II and were administered a
      diagnostic interview to establish depressive diagnoses. Results indicated that
      depressed patients demonstrated significantly greater BDI-II total scores
      compared to non-depressed patients. The recommended cutoff score of 14 for
      screening for depression appears to be appropriate for African American patients
      in the primary care setting. This cutoff yielded sensitivity of 87.7% and
      specificity of 83.9%. Positive predictive value of the BDI-II was .70, and
      negative predictive value was .94. Similar to findings with predominantly
      Caucasian samples, current results suggest the BDI-II is an appropriate and
      accurate instrument to use for depression screening among African American
      primary care patients.

PMID- 15567210
TI  - Holocaust survivors coping with open heart surgery decades later: posttraumatic
      symptoms and quality of life.
AB  - OBJECTIVE: History of prolonged traumatization has been associated with reduced
      quality of life (QoL) and difficulties in coping with major life-threatening
      conditions. We assessed the association between the impact of Holocaust
      experience (posttraumatic symptoms) and QoL of patients before and after an open
      heart surgery. METHOD: Sixty-three Holocaust survivors were interviewed before
      open heart surgery (at admission), 52 at follow-up at 1 week, and 58 at follow-up
      at 6 months. The interview included background data, Impact of Event Scale (IES),
      Mastery scale, and QoL measured by the Nottingham Health Profile. Medical data
      were retrieved from the patients' charts. RESULTS: The total IES score indicate a
      high level of posttraumatic symptoms at all the time points (close to a mean of
      18), but there was a clear trend of changes in the avoidance subscale: At
      admission, the patients manifested lower avoidance compared with the levels after
      the surgery and at the follow-up. No significant differences in IES were found by
      Holocaust experiences. Significant improvements in most components of QoL were
      found at the follow-up. In multivariate analyses at each time point, the findings
      show that those with higher levels of posttraumatic symptoms are more at risk for
      problems in pain and mobility domains of QoL at admission, for emotional reaction
      after the surgery, and at the follow-up, these associations are only at trend
      level, while lower sense of mastery became significant. CONCLUSIONS: The
      improvement in QoL despite persistence of the impact of the Holocaust may
      indicate that past severe prolonged traumatization does not necessarily reduce
      the survivors' ability to cope with and regain physical and psychosocial
      functioning after a severe life-threatening medical condition. This may be
      further generalized to other significant crisis situations in life, such as
      prolonged periods of stress, suffered by many populations throughout the world.

PMID- 15567211
TI  - The prognosis of minor depression in the general population: a systematic review.
AB  - Minor depression is common in the general population. There is no consensus about
      prognostic indicators that can identify people at high and low risk of
      chronicity. We systematically reviewed the available literature on the prognosis
      of minor depression in the general population and identified five studies. Two of
      these were considered to be of relatively high methodological quality. There was
      a wide variety among the studies in the definitions of minor depression, the
      characteristics of the study population, length of follow-up and type of outcome
      measure. The results show that the majority of people with minor depression have
      a favorable prognosis; 46-71.4% achieve remission after a follow-up of 1-6 years.
      However, 16-62.3% still have a minor depression after 5 months to 1 year of
      follow-up, suggesting that for many people minor depression is chronic or
      recurrent; 12.7-27% develop a more severe form of depression; they were diagnosed
      with dysthymia or major depression after 1-6 years of follow-up. There was
      inconsistent evidence regarding mortality and functional impairment. No study
      presented results of prognostic factors, so it remains unclear which people have
      a more favorable course than others. The results of our review need to be
      interpreted with caution because of the small number of studies and the large
      heterogeneity among studies.

PMID- 15567212
TI  - Psychological factors, pain attribution and medical morbidity in chest-pain
      patients with and without coronary artery disease.
AB  - This cross-sectional psychiatric and cardiological study compared patients with
      and without coronary artery disease (CAD) with respect to psychiatric morbidity,
      psychological factors, pain characteristics, medical morbidity and the prevalence
      of coronary risk factors. The 199 participants had been referred to cardiological
      outpatient clinics for the investigation of chest pain and had no history of
      heart disease. Current panic disorder occurred significantly more often in non
      CAD patients (41% vs. 22%). No significant differences were found for other
      psychiatric disorders and psychological variables. Non-CAD patients reported
      significantly longer histories of pain and a higher prevalence of atypical chest
      pain. In other respects, there were surprisingly few differences between the
      groups. High morbidity of both psychiatric disease (pain disorder, 19%; any
      current psychiatric disorder, 72%) and somatic conditions (musculoskeletal
      disease, 33%; dyspepsia, 23%) was found with no significant differences between
      the groups. In these patients, multifactorial complaints may explain chest pain
      in both patient groups. The physicians should attend to psychiatric disorders in
      non-CAD as well as in CAD patients.

PMID- 15567213
TI  - A study of lifetime prevalence of anxiety and depressive disorders in patients
      presenting with chest pain to emergency medicine.
AB  - We studied the prevalence of anxiety and depressive disorders in patients with
      chest pain presenting to an emergency department. Majority of the patients had
      coronary artery disease (CAD). Twenty-three percent of patients with chest pain
      had a diagnosable psychiatric disorder according to ICD-10 research criteria.
      Anxiety and depressive disorders were equally distributed among patients with
      concomitant psychiatric syndrome. The level of psychological distress as measured
      on hospital anxiety and depression scale in patients of CAD with comorbid
      psychiatric syndrome was significantly more than patients with CAD alone and
      similar to non-CAD patients with psychiatric disorder. This finding is in
      agreement with an earlier study suggesting that the psychological distress seen
      in patients with CAD is related to the comorbid psychiatric condition and not to
      CAD.

PMID- 15567214
TI  - When agreeing with the patient is not enough: a schizophrenic woman requests
      pregnancy termination.
AB  - In this article, we discuss the ethical dilemma health care providers faced when
      Rebecca, a pregnant schizophrenic patient who lacked decision-making capacity,
      inconsistently requested elective pregnancy termination. When a patient's
      decision-making capacity is severely impaired, how does the physician balance
      obligations to protect the patient from harm (beneficence) while also respecting
      her reproductive preferences and decisions (respect for autonomy)? Rebecca
      suffers from polysubstance abuse and paranoid schizophrenia characterized by
      disorganized thought and speech, auditory hallucinations, and delusional ideas.
      She arrived 14+ weeks pregnant and unaccompanied at an obstetric clinic
      requesting an abortion. This is her second and final request. On all prior and
      subsequent occasions, she was either ambivalent or said she wanted to continue
      the pregnancy. After the consulting psychiatrist determined that she lacked
      decision-making capacity, steps were taken to address ethical and clinical
      issues. The steps included treating her schizophrenia to see if she could regain
      decision-making capacity; identifying a surrogate and using a shared decision
      making model; and devising strategies to protect Rebecca and her fetus without
      resorting to excessive paternalism. Rebecca continued her pregnancy. Due to poor
      adherence to medical regimen and inadequate social support, Rebecca's
      schizophrenia was poorly controlled and she continued to use drugs during the
      pregnancy. She delivered a term baby who was soon removed from her custody.
      Despite some people's desire to protect Rebecca by complying with her request for
      abortion, we conclude that to do so would be ethically unjustified. To treat a
      decisionally impaired patient's requests for abortion as autonomous is
      disrespectful of the vulnerable patient because such paternalism fails to respect
      the patient's liberty and the surrogate's authority.

PMID- 15567215
TI  - Venous thromboembolism and escitalopram.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are currently used as a first
      line treatment for depression, as they have a favorable side-effect profile.
      Escitalopram, a new SSRI, is also well-tolerated and serious side effects are
      rarely associated with its use. There have been several reports that SSRIs might
      increase bleeding tendency in some patients by affecting platelet function.
      However, to our knowledge, there have been no reports about their relation to
      thrombosis. In this brief report, we present a case of venous thromboembolism
      associated with escitalopram in a patient with psychotic depression without any
      major risk factors for thrombosis. SSRIs might have a dual effect on platelet
      function. The immediate and early effect of SSRI use on platelets might be an
      increase be an in tendency for thrombosis, whereas the late effect after repeated
      dosing might be an increase in tendency to bleed, as suggested by previous
      literature.

PMID- 15567216
TI  - Belief in an afterlife, spiritual well-being and end-of-life despair in patients
      with advanced cancer.
AB  - Despite the plethora of research linking spirituality, religiosity and
      psychological well-being among people living with medical illnesses, the role of
      afterlife beliefs on psychological functioning has been virtually ignored. The
      present investigation assessed afterlife beliefs, spiritual well-being and
      psychological functioning at the end of life among 276 terminally ill cancer
      patients. Results indicated that belief in an afterlife was associated with lower
      levels of end-of-life despair (desire for death, hopelessness and suicidal
      ideation) but was not associated with levels of depression or anxiety. Further
      analyses indicated that when spirituality levels were controlled for, the effect
      of afterlife beliefs disappeared. The authors concluded that spirituality has a
      much more powerful effect on psychological functioning than beliefs held about an
      afterlife. Treatment implications are discussed.

PMID- 15567217
TI  - Patient attitudes toward weight gain with medications.
AB  - OBJECTIVE: The purpose of this study was to examine patient attitudes toward
      weight gain with medications under 4 conditions-medical vs psychiatric and life
      threatening vs non-life-threatening. METHOD: In a suburban primary care practice,
      241 patients completed surveys that explored the 4 study conditions and the
      amount of weight, from 0 to 20 or more pounds, willing to be gained on
      medication. RESULTS: Participants were willing to gain an average of 5.51 lb for
      a non-life-threatening medical condition, 5.37 lb for a non-life-threatening
      psychiatric condition, 13.30 lb for a life-threatening medical condition, and
      12.70 lb for a life-threatening psychiatric condition. Participants were willing
      to gain significantly more weight with a medical vs psychiatric condition and
      with a life-threatening vs non-life-threatening condition. There were no
      significant gender differences in responses. CONCLUSIONS: There appear to be
      distinct patterns of acceptability of weight gain with medications. This
      information may enhance prescribers' ability to strategize medication compliance
      among patients.

PMID- 15567218
TI  - Recurrent mania associated with repeated brain injury.

PMID- 15567219
TI  - Optimized sequence retrieval from single bands of temperature gradient gel
      electrophoresis profiles of the amplified 16S rDNA fragments from an activated
      sludge system.
AB  - Sequence retrieval from single bands of polymerase chain reaction (PCR)
      denaturing gel electrophoresis (DGE) profiles is an important but often difficult
      step for molecular diversity analysis of complex microbial communities such as
      activated sludge systems. We analyzed the temperature gradient gel
      electrophoresis (TGGE) profiles of PCR-amplified 16S rDNA fragments from an
      activated sludge sample of a coking wastewater treatment plant. Single bands were
      excised, and a clone library was constructed for each. Sequence heterogeneity in
      each single band was found to be significantly overestimated due to single
      stranded DNA (ssDNA) contamination formed during the PCR amplification, since
      only 10-60% of library clones of each single TGGE band had identical migration
      behavior compared with the parent band. Three methods, digestion with mung bean
      nuclease, optimization of PCR amplification, and purification via denatured
      polyacrylamide gel electrophoresis (d-PAGE), were compared for their ability to
      minimize ssDNA contamination, with the last one being the most efficient. After
      using d-PAGE to minimize ssDNA to a nearly nondetectable level, 70-100% of
      library clones for each single TGGE band had identical migration compared with
      the parent band. Several sequences were found in each of six single bands, and
      this co-migration could be predicted with the Poland software. The predominant
      bacteria of the activated sludge were assessed via a combination of sequence
      retrieval from each single TGGE band and band intensity analysis. Only beta and
      alpha subclasses of the Proteobacteria were detected, 93.8% and 6.2%,
      respectively. Our work suggests that prior to constructing a clone library to
      retrieve the actual sequence diversity of a single DGE band, it is advisable to
      minimize ssDNA contamination to a nondetectable level.

PMID- 15567220
TI  - Development of real-time PCR for the differential detection and quantification of
      Ureaplasma urealyticum and Ureaplasma parvum.
AB  - Ureaplasma parvum and Ureaplasma urealyticum are recently recognized species of
      the genus Ureaplasma. In humans, Ureaplasma spp. can be found on mucosal
      surfaces, primarily in the respiratory and urogenital tracts. They have been
      implicated in various human diseases such as nongonococcal urethritis,
      intrauterine infections in association with adverse pregnancy outcome and fetal
      morbidity, and pneumonitis in immunocompromised hosts. We have developed two
      quantitative real-time PCR assays to differentially detect U. parvum and U.
      urealyticum. Based upon the sequence information of the urease gene (ureB), we
      designed two TaqMan primer and probe combinations specific for U. parvum and U.
      urealyticum, respectively. The assays did not react with nucleic acid
      preparations from 16 bacterial species commonly encountered in relevant clinical
      specimens, including seven urease-producing species. Each assay had a detection
      limit of approximately five copies per reaction of the respective gene target.
      The results suggest that these assays are both sensitive and specific for U.
      parvum and U. urealyticum. Further investigation of both assays using clinical
      specimens is appropriate.

PMID- 15567221
TI  - Optimisation of the fluorescein diacetate antibacterial assay.
AB  - The fluorescein diacetate (FDA) antibacterial assay relies on the cleavage of
      fluorescein diacetate by metabolically active bacteria. The recent finding that
      microbiological media can lead to significant levels of cleavage has reduced the
      reliability of the assay. Using the nucleophilic scavengers N-ethylmaleimide and
      maleic anhydride, we have demonstrated that this abiotic cleavage is most likely
      due to nucleophiles such as cysteine and histidine commonly present in the media.
      To increase the reliability of the assay we have modified the original assay
      conditions to include use of dilute medium (peptone 0.2% w/v, yeast extract 0.1%
      w/v and NaCl 0.1% w/v) in a non-nucleophilic buffer and overnight incubation of
      the medium after addition of antibacterial agents. The optimised fluorescein
      diacetate assay has been used to determine the MIC of gentamicin, tetracycline
      and chloramphenicol for Escherichia coli, Staphyloccocus aureus and Pseudomonas
      aeruginosa and gave quantitative results that were reproducible and consistent
      with published data.

PMID- 15567222
TI  - Effect of natamycin on the enumeration, genetic structure and composition of
      bacterial community isolated from soils and soybean rhizosphere.
AB  - Natamycin is commonly used to control fungal growth on agar media used for
      bacterial enumeration or strain isolation. However, there is no conclusive report
      on the possible effect of this antibiotic on bacterial growth or on the diversity
      of the recovered soil bacteria. Therefore, the possible effects of natamycin on
      the numbers of bacteria isolated at 12 degrees C from three different soils and
      soybean rhizosphere soil were investigated using natamycin concentrations ranging
      from 0 to 200 mg l(-1). Our results demonstrate that natamycin concentrations,
      which inhibit the growth of fungi on the media, have a small but significant
      inhibitory effect on the number of bacterial colony forming units. A natamycin
      concentration of 50-200 mg l(-1) is required for an efficient control of fungal
      growth on media in our experimental conditions depending on the soil type.
      Bacterial community structure was assessed on culturable cells (cells washed from
      enumeration plates: plate-wash approach) obtained at 12 degrees C from soybean
      rhizosphere soil by performing Ribosomal Intergenic Spacer Analysis (RISA)
      fingerprinting. We demonstrate that all natamycin concentrations used alter the
      structure of the recovered, culturable bacterial community, compared to control
      without natamycin. Using ARDRA (amplification of the 16S rDNA gene and
      restriction analysis) genotyping of individual isolates, some differences were
      observed between the bacterial isolates obtained in the presence or absence of
      natamycin. Bacterial isolates recovered in the presence of natamycin are more
      tolerant (maximal growth rate and lag phase) to this compound than those isolated
      without natamycin, indicating a possible selection of resistant strains.
      Therefore, high concentration of natamycin cannot be used for isolation of
      bacterial strains with the aim of studying biodiversity and could bias a
      selection of strains for practical applications.

PMID- 15567223
TI  - Activity-dependent fluorescent labeling of bacterial cells expressing the TOL
      pathway.
AB  - 3-Ethynylbenzoate (3EB) functions as a novel, activity-dependent, fluorogenic,
      and chromogenic probe for bacterial strains expressing the TOL pathway, which
      degrade toluene via conversion to benzoate, followed by meta ring fission of the
      intermediate catechol. This direct physiological analysis allows the fluorescent
      labeling of cells whose toluene-degrading enzymes have been induced by an
      aromatic substrate.

PMID- 15567224
TI  - Direct detection of Staphylococcus aureus mRNA using a flow through microarray.
AB  - The direct detection of mRNAs from bacterial cultures on a DNA array without
      amplification and labelling would greatly extend the range of applications
      suitable for microarray analysis. Here we describe the direct detection of 23S
      rRNA and seven mRNA species from total Staphylococcus aureus RNA prepared using
      commercially available RNA purification columns followed by fluorescent detection
      on a flow through microarray. RNA hybridisation was detected using paired
      secondary labelled probes directly 5' and 3' to immobilised 60 mers. In this way,
      we were able to detect the effect of 30-min exposure to antimicrobials on mRNA
      levels within 3 h after column purification of total RNA without the need for
      enzymatic manipulation. Specifically the expression of mecA was confirmed in a
      highly resistant strain and induction of katA and ile-tRNA synthetase genes after
      exposure to mupirocin could be detected.

PMID- 15567225
TI  - A rapid microplate method for quantifying inhibition of bacterial adhesion to
      eukaryotic cells.
AB  - Adhesion of bacteria to the mucosal epithelial cell surface is the first step in
      infection, and studies have shown that inhibition of this step may be useful
      therapeutically. To test compounds that may prevent bacterial binding to a number
      of epithelial cell lines, we have developed a high-throughput adhesion assay
      using a microtitre plate system and bacteria that have been modified to express
      firefly luciferase. This method has proved to be a sensitive, rapid, and
      reproducible system for screening antiadhesive agents for their effects on
      bacterial adhesion.

PMID- 15567226
TI  - Culture independent PCR: an alternative enzyme discovery strategy.
AB  - Degenerate primers were designed for use in a culture-independent PCR screening
      of DNA from composite fungal communities, inhabiting residues of corn stovers and
      leaves. According to similarity searches and alignments amplified clone sequences
      affiliated with glycosyl hydrolase family 7 and glycosyl hydrolase family 45
      though significant sequence divergence was observed. Glycosyl hydrolases from
      families 7 and 45 play a crucial role in biomass conversion to fuel ethanol.
      Research in this renewable energy source has two objectives: (i) To contribute to
      development of a renewable alternative to world's limited crude fossil oil
      reserves and (ii) to reduce air pollution. Amplification with 18S rDNA-specific
      primers revealed species within the ascomycetous orders Sordariales and
      Hypocreales as well as basidiomycetous order Agaricales to be present in these
      communities. Our study documents the value of culture-independent PCR in
      microbial diversity studies and could add to development of a new enzyme
      screening technology.

PMID- 15567227
TI  - Development of real-time PCR using Minor Groove Binding probe to monitor the
      biological control agent Candida oleophila (strain O).
AB  - A real-time PCR assay using a 3'-Minor Groove Binding (MGB) probe was developed
      for specific detection and monitoring of Candida oleophila (strain O), a
      biocontrol agent against Botrytis cinerea and Penicillium expansum, on harvested
      apples. The application of the RAPD technique on C. oleophila strains followed by
      reproducible sequence characterized amplified region (SCAR) amplifications
      allowed the identification of a semi-specific fragment of 244 bp, observed in the
      profiles of strain O and three other C. oleophila strains. After sequencing,
      polymorphisms (3%) were observed between the strain O sequence and the three
      other sequences. A 3'-Minor Groove Binding probe was designed to specifically
      match a region of the strain O sequence and was able to discriminate a single
      base mutation or a two-base difference in the corresponding sequences of the non
      target strains. This specific detection method was applied to monitor strain O
      population, recovered by a washing buffer, from harvested apples. Population
      densities were calculated using an external standard curve consisting in a serial
      dilution of strain O cells in the washing buffer from untreated apples. Linearity
      in the standard curve was kept between 1.64 x 10(2) and 1.64 x 10(5) cfu cm(-2)
      of apple surface. During a first practical experiment, the calculated population
      densities were similar to those obtained by plating on semi-selective media. This
      new real-time PCR method is a promising tool to monitor quickly and specifically
      strain O population on apple surface in middle- or large-scale experiments.

PMID- 15567228
TI  - Capillary electrophoresis single-strand conformation polymorphism analysis for
      monitoring soil bacteria.
AB  - The ability to effectively monitor a microbial community is necessary to design
      and implement remediation strategies for contaminated soil. Single-strand
      conformation polymorphism (SSCP), a technique which separates DNA fragments based
      on their sequence, was used to analyze amplified 16S rRNA gene fragments of 12
      common soil bacteria. Separation was performed using capillary electrophoresis
      (CE), as opposed to other common gel techniques, to eliminate the need for band
      analysis on gel matrices. Four different universal bacterial primer sets were
      used for DNA amplification: 341-534, P11-P13, Er10-Er11, and Er14-Er15
      corresponding to the V3, V8, V2, and V4 regions, respectively. The forward strand
      of each primer was labeled with 6-carboxy fluorescein fluorescent dye. Analyses
      were performed on the Applied Biosystems 310 genetic analyzer using GeneScan
      Analysis Software version 3.5. The best results were obtained using primer 341
      534, in which 6 of the 12 bacteria could be distinguished. By combining primer
      sets 341-534 and Er10-Er11, all 12 of the bacteria could be separated, indicating
      various degrees of polymorphism within the selected primer regions. When
      performing simultaneous amplification and analysis of all 12 species some
      preferential amplification occurred, as not all peaks could be observed. However,
      SSCP profiles obtained for pure bacterial cultures show the potential of CE-SSCP
      for bacterial community analysis.

PMID- 15567229
TI  - Multiplex PCR-DNA probe assay for the detection of pathogenic Escherichia coli.
AB  - A multiplex PCR-DNA probing assay was developed to detect four major Escherichia
      coli virotypes. Six highly specific polymerase chain reaction (PCR) primer sets
      and DIG-labeled chemiluminescent probes were designed to target the Shiga-like
      toxin I and II genes (stxI and stxII) of verotoxigenic E. coli (VTEC), heat
      stable and heat-labile toxin genes of enterotoxigenic E. coli (ETEC), adherence
      factor (EAF) of enteropathogenic E. coli (EPEC) and a fragment of the
      invasiveness plasmid (IAL) of enteroinvasive E. coli (EIEC). The primer pairs
      generate products of 350, 262, 170, 322, 293 and 390 bp in length, respectively.
      The multiplex primers and probes were tested for specificity against 31
      pathogenic E. coli strains, nine nonpathogenic E. coli and non-E.coli enteric and
      environmental bacterial strains. The results showed a high degree of specificity
      of the primers and probes for strains from corresponding virotypes and no
      reaction with the nontarget bacterial strains. The proposed multiplex PCR-DNA
      probing assay provides rapid and specific detection of four major virotypes of E.
      coli.

PMID- 15567230
TI  - McRAPD as a new approach to rapid and accurate identification of pathogenic
      yeasts.
AB  - Despite advances in antifungal prophylaxis and therapy, morbidity and mortality
      incurred by yeasts remain a significant burden. As pathogenic yeast species vary
      in their susceptibilities to antifungal agents, clinical microbiology
      laboratories face an important challenge to identify them rapidly and accurately.
      Although a vast array of phenotyping and genotyping methods has been developed,
      these are either unable to cover the whole spectrum of potential yeast pathogens
      or can do this only in a rather costly or laborious way. Random amplified
      polymorphic DNA (RAPD) fingerprinting was repeatedly demonstrated to be a
      convenient tool for species identification in pathogenic yeasts. However, its
      wider acceptance has been limited mainly due to special expertise and software
      needed for analysis and comparison of the resulting banding patterns. Based on a
      pilot study, we demonstrate here that a simple and rapid melting curve analysis
      of RAPD products can provide data for identification of five of the most
      medically important Candida species. We have termed this new approach melting
      curve of random amplified polymorphic DNA (McRAPD) to emphasize its rapidity and
      potential for automation, highly desirable features for a routine laboratory
      test.

PMID- 15567231
TI  - Development of PCR primers specific for the amplification and direct sequencing
      of gyrB genes from microbacteria, order Actinomycetales.
AB  - PCR primer sets were developed for the specific amplification and sequence
      analyses encoding the gyrase subunit B (gyrB) of members of the family
      Microbacteriaceae, class Actinobacteria. The family contains species highly
      related by 16S rRNA gene sequence analyses. In order to test if the gene sequence
      analysis of gyrB is appropriate to discriminate between closely related species,
      we evaluate the 16S rRNA gene phylogeny of its members. As the published
      universal primer set for gyrB failed to amplify the responding gene of the
      majority of the 80 type strains of the family, three new primer sets were
      identified that generated fragments with a composite sequence length of about 900
      nt. However, the amplification of all three fragments was successful only in 25%
      of the 80 type strains. In this study, the substitution frequencies in genes
      encoding gyrase and 16S rDNA were compared for 10 strains of nine genera. The
      frequency of gyrB nucleotide substitution is significantly higher than that of
      the 16S rDNA, and no linear correlation exists between the similarities of both
      molecules among members of the Microbacteriaceae. The phylogenetic analyses using
      the gyrB sequences provide higher resolution than using 16S rDNA sequences and
      seem able to discriminate between closely related species.

PMID- 15567232
TI  - Reliability of the Amplicor internal control to disclose false-negative Chlamydia
      trachomatis PCR results.
AB  - Four possibly false-negative samples were detected when 514 male urine specimens
      were tested in the Amplicor Chlamydia trachomatis assay. In three of the four
      samples, the inhibition could be reduced by removal of urine supernatant. Under
      partially inhibitory conditions, after spiking with 50 C. trachomatis elementary
      bodies/ml specimen, a selective inhibition of the C. trachomatis target
      amplification and a preferential internal control amplification was observed. We
      conclude that a positive internal control signal might be misleading in
      inhibitory specimens with low amount of C. trachomatis.

PMID- 15567233
TI  - A simple and economic preservation method for genomic bacterial DNA from
      clinically significant pathogens.
AB  - Bacterial culture was allowed to dry to completeness on Columbia agar base with
      defibrinated horse blood. Following 6 months storage at room temperature,
      microbial DNA was extracted and successfully amplified by PCR. This storage
      technique has the advantage over other methods of not requiring (i) a DNA
      extraction protocol prior to storage and (ii) refrigeration and/or freezing. This
      technique maybe useful in the transportation of bacterial genomic DNA in
      nonviable cells as well as reliable method for the storage of DNA in
      underdeveloped countries.

PMID- 15567234
TI  - A simple imaging method for biomass determination.
AB  - An inexpensive and fast method based on images taken during growth of bacterial
      cells on multi-well plates was developed for biomass quantification. A
      correlation of 85% between the results obtained by image analysis and optical
      density measurements was obtained. This simple method allows the assessment of
      growth with highly aggregated cell cultures and the rapid screening of a large
      number of carbon sources.

PMID- 15567235
TI  - Antioxidant lignan glucosides from Strychnos vanprukii.
AB  - From the stem of Strychnos vanprukii, two new lignan glucosides, vanprukoside (1)
      and strychnoside (2), were isolated together with the known lignan glucoside, (+)
      lyoniresinol-3 alpha-O-beta-glucopyranoside (3). The structures of these
      compounds were elucidated on the basis of their spectroscopic data. All three
      compounds exhibited antioxidant activity.

PMID- 15567236
TI  - Antiplatelet activity of Varthemia iphionoides.
AB  - Aqueous and alcoholic extracts, volatile oil and four flavonoids, xanthomicrol
      (1), kumatokenin (2), jaceidin (3) and 3, 3'-di-O-methylquercetin (4), isolated
      from Varthemia iphionoides were investigated for their in vitro anti-platelet
      activity. Aqueous extract and compounds (1), (2) and (4) showed anti-platelet
      activity. Volatile oil and the alcoholic extract did not exhibit any anti
      platelet activity. Structures of the isolated compounds (1)-(4) were determined
      by spectroscopic methods (UV, IR, MS, (1)H-NMR).

PMID- 15567237
TI  - Saponins from Furcraea selloa var. marginata.
AB  - Four steroidal saponins were isolated from the leaves of Furcraea selloa var.
      marginata. These included one furostanol saponin, furcreafurostatin (1), and
      three known spirostanol saponins, furcreastatin (3), yuccaloeside C (4) and
      cantalasaponin-1 (5). The 22-O-methyl ether (2) of furcreafurostatin (1) was also
      characterized. The structures were determined by using a combination of
      spectroscopic techniques.

PMID- 15567238
TI  - Antiproliferative activity of Goldfussia psilostachys ethanolic extract on K562
      leukemia cells.
AB  - A dose-dependent and significant (P<0.01) antiproliferative effect of Goldfussia
      psilostachys ethanolic extract was observed on K562 cells. The IC(50) is ca. 0.5
      microg/ml. The extract markedly increases the proportion of cell in G2/M phases
      and decreases the population of cells in G0/G1 phases. Moreover, the antimitotic
      effect is correlated with polymerization of microtubule assembly. These results
      indicate that G. psilostachys ethanolic extract inhibits the proliferation of
      K562 cells and disrupts the normal dynamic of microtubules during mitosis.

PMID- 15567239
TI  - Morphological evidences for onion-induced growth inhibition of Trichophyton
      rubrum and Trichophyton mentagrophytes.
AB  - The antifungal activity of onion (Allium cepa L.) on two important dermatophytes,
      Trichophyton rubrum and Trichophyton mentagrophytes, with special reference to
      morphological aspects was studied. Growth of both fungi was found to be strongly
      inhibited by aqueous onion extract (AOE) as a dose-dependent manner. The extract
      showed fungicidal effect for both fungi at concentrations >3.12% (v/v). The
      fungus T. mentagrophytes was more affected by the onion as compared to T. rubrum
      at all concentrations used. Morphological effects of onion exposure were examined
      in correlation with fungal growth. Corresponding to the growth inhibition, light
      and electron microscopy observations revealed morphological anomalies in hyphal
      compartments. The results demonstrated that AOE targets the cell membrane of the
      fungi as breaking down of both inner and outer membranes with consequent
      extrution of materials into the surrounding medium. Cytoplasmic membranes and
      other membranous structures of organelles, such as nuclei and mitochondria, were
      also disrupted. In correlation to the fungal growth, morphological alterations
      occurred to a less content for T. rubrum compared with T. mentagrophytes. The
      hyphae of T. rubrum were found to be mainly affected by converting to resistant
      forms, i.e., chlamidospores as a consequence of phenotype switching response to
      AOE. Plasmolysis accompanied by an almost complete depletion and disorganization
      of cytoplasmic structures were found to be the final event which led to cell
      death. Ultrastructural evidences obtained from this study strongly support that
      morphological changes of T. rubrum and T. mentagrophytes caused by AOE are
      associated with its fungistatic and fungicidal activities. With respect to the
      morphological results and the preliminary data on fungal biochemistry, a
      mechanism of action by interacting of AOE with thiol (-SH) groups present in
      essential compartments of the fungal cells was postulated.

PMID- 15567240
TI  - Supercritical fluid extraction of sapogenins from tubers of Smilax china.
AB  - Supercritical CO(2) fluid extraction (SFE-CO(2)) was used to extract the
      sapogenins after acid hydrolysis from Smilax china tubers. The influence of
      extraction variables, such as modifier, pressure, temperature and extraction
      time, were studied. SFE-CO(2) was found to produce higher yield than conventional
      solvent extraction. The highest yield (0.454%) of sapogenins, mostly containing
      diosgenin, was obtained using 35 MPa pressure, 65 degrees C and 95% EtOH as a
      modifier for 180 min, higher than that obtained with conventional extraction
      methods (0.385%).

PMID- 15567241
TI  - Isolation, purification and identification of polysaccharides from cultured
      Cordyceps militaris.
AB  - Four polysaccharides from the water extract of cultured Cordyceps militaris were
      isolated through ethanol precipitation, deproteination and gel-filtration
      chromatography. Their molecular weights were determined using gel-filtration
      chromatography. Among the four isolated polysaccharides, the structures of two of
      them (CPS-2 and CPS-3) were elucidated by sugar analysis, Smith degradation, IR
      and (13)C-NMR spectroscopy.

PMID- 15567242
TI  - Antinociceptive effect of Melastoma malabathricum ethanolic extract in mice.
AB  - The antinociceptive effect of the ethanolic extract of Melastoma malabathricum
      (MME) was investigated using acetic acid-induced abdominal writhing test and hot
      plate test in mice. It was demonstrated that the extract (30-300 mg/kg, i.p.)
      strongly and dose-dependently inhibited the acetic acid-induced writhing with an
      ED(50) of 100 (78-160) mg/kg i.p. It also significantly increased the response
      latency period to thermal stimuli. Furthermore, the nonselective opioid receptor
      antagonist, naloxone blocked the antinociceptive effect of the extract in both
      tests, suggesting that M. malabathricum may act both at peripheral and central
      levels.

PMID- 15567243
TI  - CNS activity of Alstonia macrophylla leaf extracts: an ethnomedicine of Onge of
      Bay Islands.
AB  - Methanol extract at 100-200 mg/kg p.o. and major nonpolar fraction B at 50 mg/kg
      of Alstonia macrophylla leaves caused a significant reduction in spontaneous
      activity, remarkable decrease in exploratory behavioural pattern, a reduction in
      muscle relaxant activity and also significantly potentiated phenobarbitone sodium
      induced sleeping time. The phytochemical study of crude leaf extract revealed the
      presence of tannin, triterpenoid, flavonoid, sterol, alkaloid and reducing
      sugars. Further fractionation and purification of the n-butanol part of methanol
      extract yielded fraction A, fraction B and fraction C along with some minor fatty
      acids as the major compounds.

PMID- 15567244
TI  - New polyisoprenylated benzophenones from Venezuelan propolis.
AB  - Two new polyisoprenylated benzophenones, 18-ethyloxy-17-hydroxy-17,18
      dihydroscrobiculatone A and 18-ethyloxy-17-hydroxy-17,18-dihydroscrobiculatone B,
      together with the known scrobiculatones A and B, were isolated from Venezuelan
      propolis. The scrobiculatones A and B showed significant antibacterial activity
      and moderate toxicity to Artemia salina nauplii.

PMID- 15567245
TI  - Spasmolytic stilbenoids from Maxillaria densa.
AB  - 2,5-dihydroxy-3,4-dimethoxyphenanthrene (1), fimbriol-A (2), nudol (3),
      gymnopusin (4) and erianthridin (5) isolated from Maxillaria densa provoked a
      concentration-dependent inhibition of the spontaneous contractions of the rat
      ileum with potencies comparable to papaverine. In order to establish the mode of
      action of stilbenoids 1-5, their effect on the contractions induced by different
      spasmogens (histamine, barium chloride and L-NAME) was investigated. In general,
      the results suggested that the relaxant activity of the products does not involve
      a direct nitrergic or antihistaminergic mode of action or an interference with
      calcium influx into the smooth muscle cells.

PMID- 15567246
TI  - Analysis of essential oils from wild and micropropagated plants of damiana
      (Turnera diffusa).
AB  - Damiana is a medicinal plant with many traditional uses and a reputation as an
      aphrodisiac. Essential oils produced by this plant are used in traditional
      medicine, and for the preparation of liquors and tea. The composition of
      essential oils from wild damiana, plants grown with micropropagated methods
      involving cell suspension, and explants in solid medium, is presented. Relevant
      differences are observed in oils coming from wild and micropropagated plants,
      where micropropagated plants being more uniform with respect to quality and
      quantity. The most abundant constituents of the oils were caryophyllene oxide,
      caryophyllene, delta-cadinene, elemene and 1,8-cineol.

PMID- 15567247
TI  - Morphological, histochemical and phytochemical investigation of the genus
      Hypericum of the Central Italy.
AB  - Eight entities of the genus Hypericum that spontaneously grow on the Central
      Italy (Appennino Umbro-Marchigiano) have been studied under the morphological,
      histochemical and phytochemical aspects. From the morphological standpoint, they
      differ in the shape and size of flowers and leaves and in the dimension and
      distribution of the secretory structures through the various parts of the plant.
      It has been possible, with the histochemical and phytochemical studies, to
      localize and identify some secondary metabolites inside the secretory structures.

PMID- 15567248
TI  - Effects of the plant alkaloid thaliblastine on non-cross-resistant and sensitive
      human leukemia cells in relation with reversal of acquired anthracycline
      resistance.
AB  - Thaliblastine exhibits dose dependent cytotoxic effect on HL-60, HL-60/DOX, RHE
      and HD-MY-2 leukemia cells. Additionally, typical for apoptosis oligonucleosomal
      DNA fragmentation could be detected in leukemia cells treated with thaliblastine.
      Moreover, an MDR-phenotype reversing effect of thaliblastine was also identified.

PMID- 15567249
TI  - Inhibition of Trypanosoma cruzi by plant extracts used in Chinese medicine.
AB  - In this work, we assessed the effect of extracts obtained from 17 plants used in
      traditional Chinese medicine. These extracts were tested in vitro with the
      epimastigote form of Trypanosoma cruzi, clone Bra C(15) C(2), at 27 degrees C in
      F-29 medium at a concentration of 100 microg/ml in axenic cultures. Allopurinol
      was used as reference drug. Seven plant extracts showed inhibitory activities
      lower than 25%. Pueraria lobata, Mahonia beaei, Dictamus dasycarpus, Kochia
      scoparia, Sophora flavescens and Ligustrum lucidum showed effects with inhibition
      values between 25% and 60%, whereas Lithospermum erythrorhizon, Saussurea lappa,
      Melia toosendan and Cinnamomum cassia showed the greatest inhibitory activity of
      100%. The IC(50) of these extracts were: 0.4, 2.4, 1.8 and 3.9 microg/ml,
      respectively. The MTT assay was made and did not show cytotoxic activity. These
      results allowed us to suggest that L. erythrorhizon, S. lappa, M. toosendan and
      C. cassia could be a source of new compounds against T. cruzi.

PMID- 15567250
TI  - Larvicidal activity of a botanical natural product, AkseBio2, against Culex
      pipiens.
AB  - A botanical natural product, AkseBio2, was evaluated for its larvicidal effect
      against Culex pipiens under laboratory conditions. The product exhibited strong
      larvicidal activity and caused >90% mortalities in both the young (first-second)
      and the older (third-fourth) larval stages of the species at 24 h at the doses of
      25 and 50 ppm. However, it was determined that the young larval stages were more
      susceptible to the product in comparison with the older larval stages. The
      results suggest that the product is promising as a larvicide against C. pipiens
      and could be useful in the search of new larvicidal natural compounds.

PMID- 15567251
TI  - Phytochemical and antimicrobial activities of the Daniellia oliveri leaves.
AB  - The n-butanol soluble part and four chromatographic fractions of the aqueous
      ethanolic extract of the leaves of Daniellia oliveri were investigated for
      antimicrobial properties. All fractions showed activity against Staphylococcus
      aureus. A chromatographic fraction showed significant activity against the fungus
      Tricophyton rubrum.

PMID- 15567252
TI  - Antibacterial activity of Achillea clavennae essential oil against respiratory
      tract pathogens.
AB  - The essential oil of Achillea clavennae was investigated for its antibacterial
      activity against some respiratory tract pathogens. Maximum activity was observed
      against Klebsiella pneumoniae and penicillin-susceptible and penicillin-resistant
      Streptococcus pneumoniae. The oil also exhibited strong activity against Gram (-)
      Haemophilus influenzae and Pseudomonas aeruginosa. Gram (+) Streptococcus
      pyogenes was the most resistant to the oil.

PMID- 15567253
TI  - Antibacterial activity of Cichorium intybus.
AB  - Antibacterial activity of the water, ethanol and ethyl acetate extracts of
      Cichorium intybus was investigated. All the tested extracts showed antibacterial
      activity, the ethyl acetate extract being the most active. Water extract inhibits
      Agrobacterium radiobacter sp. tumefaciens, Erwinia carotovora, Pseudomonas
      fluorescens and P. aeruginosa.

PMID- 15567254
TI  - Anti-inflammatory and antinociceptive activities of Trewia polycarpa roots.
AB  - The alcoholic extract of Trewia polycarpa roots, when administered orally to rats
      at doses of 50-400 mg/kg, exhibited a dose-dependent anti-inflammatory activity
      in both acute and chronic models. It also showed a significant antinociceptive
      action mice in the dose range of 25-200 mg/kg. The extract did not reveal any
      toxicity in rats up to a dose of 3.2 g/kg (p.o.). It showed the presence of
      terpenoids, alkaloids, flavonoids, quinones and glycosides on phytochemical
      screening.

PMID- 15567255
TI  - Insecticidal activity of certain medicinal plants.
AB  - The methanol extracts of eight species of medicinal plants were tested for
      insecticidal activity in third instar larvae of Egyptian cottonworm (Spodoptera
      littoralis). All extracts showed a certain degree of larval toxicity. The
      extracts of Ocimum basilicum, Origanum majorana and Salvia officinalis appeared
      to be highly toxic. The extracts significantly affected the growth indexes
      [relative growth rate (RGR), efficiency of conversion of ingested food (ECI),
      efficiency of conversion of digested food (ECD)].

PMID- 15567256
TI  - Antimicrobial activity of alkaloidal fraction from barks of Himatanthus
      lancifolius.
AB  - The alkaloidal fraction from Himatanthus lancifolius barks demonstrated a broad
      spectrum in vitro antimicrobial activity for most of the Gram (+) and Gram (-)
      tested microorganisms.

PMID- 15567257
TI  - Antimicrobial and free radical scavenging activity of Gentianella nitida.
AB  - The antimicrobial and free radical scavenging activity of the ethanol extract and
      fractions of Gentianella nitida have been assessed. The most susceptible
      microorganisms were Candida albicans, Trichophyton mentagrophytes and Microsporum
      gypseum. The antifungal activity was concentrated in the 90% methanol and
      nonsoluble fractions, while the radical scavenging activity was stronger in the
      ethyl acetate and nonsoluble fractions.

PMID- 15567258
TI  - Antibacterial activity of the essential oil from Ferula gummosa seed.
AB  - Antibacterial activity of Ferula gummosa essential oil was studied against
      bacterial laboratory ATCC standards using the disk diffusion method. The results
      showed activity against Gram(+) bacteria and Escherichia coli. Little
      antibacterial activity was found against Pseudomonas aeruginosa.

PMID- 15567259
TI  - The bifidogenic effect of Taraxacum officinale root.
AB  - The infusion of dandelion root (Taraxacum officinale) stimulated in vitro the
      growth of 14 strains of bifidobacteria. The utilization of oligofructans,
      glucose, fructose and total saccharides was determined by enzymatic and phenol
      sulfuric methods. Dandelion oligofructans were important source of carbon and
      energy for bifidobacteria tested.

PMID- 15567260
TI  - A bioactive biflavonoid from Campnosperma panamense.
AB  - Lanaroflavone (1), a biflavonoid isolated from the methanol extract of the aerial
      part of Campnosperma panamense by bioguided fractionation, has been assessed for
      in vitro antiprotozoal activity. Lanaroflavone showed both antimalarial and
      leishmanicidal activities, but was inactive against Chagas disease vector,
      Trypanosoma cruzi.

PMID- 15567261
TI  - Antimicrobial activity of crude methanolic extract of Satureja khuzistanica.
AB  - The methanolic extract of the aerial parts of Satureja khuzistanica was
      investigated for its antimicrobial activity. The maximum antibacterial and
      antifungal activities were observed against Staphylococcus aureus and Candida
      albicans.

PMID- 15567262
TI  - Isolation and NMR spectra of syringaresinol-beta-D-glucoside from Cressa cretica.
AB  - The isolation, (1)H-NMR and revised (13)C-NMR assignments of syringaresinol-beta
      D-glucoside from Cressa cretica are reported.

PMID- 15567263
TI  - Isolation and X-ray crystal structure of a new isoquinoline-N-oxide alkaloid from
      Calycotome villosa subsp. intermedia.
AB  - A new isoquinoline-N-oxide alkaloid was extracted from the alkaloid fraction of a
      methanol extract of the seeds of Calycotome villosa subsp. intermedia. Its
      structure was established as 1-hydroxymethyl-6,7-dimethoxyisoquinoline-N-oxide
      (1) by spectroscopic techniques and X-ray diffraction analysis.

PMID- 15567264
TI  - A new cardenolide from the roots of Streptocaulon tomentosum.
AB  - A new cardenolide, (17 alpha)-H-periplogenin-3-O-beta-D-glucopyranosyl-(1-4)-2-O
      acetyl-3-O-methyl-beta-fucopyranoside (1), was isolated from the roots of
      Streptocaulon tomentosum.

PMID- 15567265
TI  - Arbutin-2'-sulphonyl from the infusion of Ilex theezans leaves.
AB  - A sulphate arbutin derivative was isolated from the leaves of Ilex theezans, an
      adulterant of mate (Ilex paraguariensis). The structure was determined by
      spectral analysis.

PMID- 15567266
TI  - A new diglycosyl megastigmane from Carallia brachiata.
AB  - A new megastigmane diglycoside was isolated from the leaves of Carallia
      brachiata. The structure was determined by spectroscopic methods as 3-hydroxy-5,6
      epoxy-beta-ionol -3-O-beta-apiofuranosyl-(1-->6)-beta-glucopyranoside (1).
      Additionally, 29 known compounds consisting of two megastigmanes, one 1,2
      dithiolane derivative, seven aromatic compounds, five condensed tannins, 12
      flavonoids, and two glyceroglycolipids were isolated and identified.

PMID- 15567267
TI  - Trans-2,2',4,4'-tetramethyl-6,6'-dinitroazobenzene from Aconitum sungpanense.
AB  - Trans-2,2',4,4'-tetramethyl-6,6'-dinitroazobenzene from the leaves of Aconitum
      sungpanense was reported as a new compound. The structure was determined by
      spectroscopic methods and X-ray diffraction analysis.

PMID- 15567268
TI  - Morphinandienone alkaloids from Dehaasia longipedicellata.
AB  - Five morphinoid alkaloids have been isolated from Dehaasia longipedicellata,
      namely (-) pallidine, a new alkaloid (+) pallidinine (1), (+)-milonine, (-) 8,14
      dehydrosalutaridine and (-) sinoacutine.

PMID- 15567269
TI  - A new sesquiterpene from the fruits of Allophylus laevigatus.
AB  - From the fruits of Allophylus laevigatus a new sesquiterpene, 11-acetoxy-4 alpha
      methoxyeudesmane, was isolated alongwith the known compounds carissone and
      apigenin-8-C-beta-rhamnopyranoside. The flavone showed no antioxidant activity in
      the autoxidation of beta-carotene assay.

PMID- 15567270
TI  - A new flavan from Daphne odora var. atrocaulis.
AB  - The isolation of a new flavan, 5,7,4'-trihydroxy-8-ethoxycarbonylflavan (1), from
      the root of Daphne odora var. atrocaulis is reported.

PMID- 15567271
TI  - Constituents of aromatic plants: carvacrol.
AB  - Carvacrol is a component of numerous aromatic plants. Up to now, no toxicological
      data were available. Carvacrol show a weak activity in the mutagenicity studies.
      Moreover, in the metabolism study, carvacrol has shown to be excreted with urine
      after 24 h in large quantities or unchanged or as glucoronide and sulphate
      conjugates. The available data do not allow the assessment of the NOEL. Further
      toxicological studies are needed.

PMID- 15567272
TI  - Adaptive mechanisms of nitrogen and carbon assimilatory pathways in the marine
      cyanobacteria Prochlorococcus.
AB  - Prochlorococcus is an abundant marine cyanobacterium responsible for a
      significant part of global primary production. There exist various ecotypes
      adapted to conditions found along the water column, showing that largely modified
      photosynthetic apparatus efficiently harvest the light energy penetrating into
      their habitats. In view of the recent availability of three Prochlorococcus
      genomes, we review here additional adaptive changes observed in nitrogen and
      carbon metabolism.

PMID- 15567273
TI  - Dissecting the twin-arginine translocation pathway using genome-wide analysis.
AB  - A recently discovered route for protein export, known as the twin-arginine
      translocation (Tat) pathway, has received much attention owing to several
      atypical characteristics that distinguish it from other transport mechanisms. For
      instance, recent evidence has clearly established that this pathway only
      transports folded polypeptides. Moreover, several studies have demonstrated a
      vital role for the Tat pathway in bacterial pathogenesis. In this review, we
      discuss genomic approaches that have been employed to determine the prevalence
      and capacity of the Tat system and how the information generated from these
      approaches is helping to connect Tat transport to bacterial physiology and
      virulence.

PMID- 15567274
TI  - Extracellular enzymes serving as virulence factors in nematophagous fungi
      involved in infection of the host.
AB  - Extracellular enzymes, including serine protease, chitinase and collagenase,
      corresponding to the main chemical constituents of the nematode cuticle and
      eggshell, have been reported to be involved in the infectious process as
      virulence factors. This review will focus on the categories, characterization,
      purification, cloning and potential function of these virulence enzymes and will
      attempt to provide new insights into the mechanisms of fungal pathogenesis in
      nematodes.

PMID- 15567275
TI  - Identification and semi-quantitative analysis of Mycobacterium tuberculosis H37Rv
      ftsZ gene-specific promoter activity-containing regions.
AB  - The cytokinetic protein FtsZ plays a pivotal role in regulation of cell division
      in bacteria. Multiple promoters regulate transcription of the ftsZ gene in
      Escherichia coli, Streptomyces and Bacillus species. In order to identify
      promoter activity-containing regions of the ftsZ gene of Mycobacterium
      tuberculosis H37Rv (MtftsZ) in vivo, different regions upstream of MtftsZ,
      namely, the ftsQ-ftsZ intergenic region, the ftsQ open reading frame (ORF), and
      different regions of ftsQ ORF, were analyzed in a gfp reporter plasmid in
      Mycobacterium smegmatis mc(2)155 cells. Flow cytometric analysis of mid
      logarithmic M. smegmatis mc(2)155 cells containing these transcription fusion
      constructs revealed GFP expression in the cells harboring the ftsQ-ftsZ
      intergenic region (172 bp), the entire ftsQ ORF (945 bp), and 5' 467-bp and 3'
      217-bp regions of ftsQ ORF. RT-PCR analyses on RNA from M. smegmatis mc(2)155
      cells, transformed with the entire ftsQ ORF-ftsQ-ftsZ intergenic region
      containing construct, as well as on RNA from M. tuberculosis, confirmed that the
      regions identified indeed elicit promoter activity. Semi-quantitative RT-PCR
      analyses of gfp transcripts driven by cloned MtftsZ promoter regions in M.
      smegmatis cells showed threefold higher promoter activity from ftsQ ORF than from
      the ftsQ-ftsZ intergenic region. Expression from the individual 5' and 3' regions
      of ftsQ ORF was almost equivalent to that from the ftsQ-ftsZ intergenic region.
      RT-PCR analyses on RNA from M. tuberculosis quantitatively confirmed these
      promoter activities. Thus, at least three independent regions in the immediate
      upstream sequence of MtftsZ contain promoter activity, with the major
      contribution coming from ftsQ ORF.

PMID- 15567276
TI  - An unusually high level of quinolone resistance associated with type II
      topoisomerase mutations in quinolone resistance-determining regions of Aeromonas
      caviae isolated from diarrhoeal patients.
AB  - We examined 158 strains belonging to different Aeromonas species isolated from
      hospitalized acute diarrhoea cases for susceptibility to quinolones. Compared to
      other species, a high percentage of the A. caviae strains were resistant to
      ciprofloxacin and norfloxacin. Based on MIC values, 6 A. caviae strains were
      selected and the nucleotide sequences for the quinolone-resistant-determining
      regions (QRDRs) of gyrA, gyrB and parC genes were analysed. In resistant strains,
      double mutations (Ser(83)-->Ile and Asp(87)-->Asn) and a single mutation (Ser(80)
      ->Ile) were detected in the QRDR of gyrA and parC, respectively.

PMID- 15567277
TI  - Characterisation of rpsL, rrs and embB mutations associated with streptomycin and
      ethambutol resistance in Mycobacterium tuberculosis.
AB  - In order to characterise molecular mechanisms of first-line drug resistance in
      Mycobacterium tuberculosis and to evaluate the use of molecular markers of
      resistance (gene point mutations), we analysed 66 multi-drug-resistant (MDR)
      isolates from Latvian tuberculosis patients. They were all resistant to rifampin
      (RIF), isoniazid (INH) and streptomycin (SM), and 33 were resistant to ethambutol
      (EMB). Enzymatic digestion by MboII and nucleotide sequencing of the rpsL gene
      fragment detected a single nucleotide substitution K43R in 40 (61%) of the 66 SM
      resistant M. tuberculosis isolates. Of the other 26 SM-resistant isolates, 16
      (24%) had mutations at positions 513A-->C and 516C-->T of the rrs gene and 10
      (15%) had the wild-type sequence. The single-stranded DNA conformation
      polymorphism (SSCP) method was used to detect mutations in the embB gene
      associated with EMB resistance. Substitutions in the embB gene were found by SSCP
      analysis in 15 (45%) and by sequencing in 17 (52%) of the 33 EMB-resistant
      isolates. Surprisingly, SSCP revealed a nucleotide mutation at codon M306 in five
      (15%) of 33 in vitro EMB-susceptible MDR isolates.

PMID- 15567278
TI  - Proteomic analysis of salt-sensitive outer membrane proteins of Vibrio
      parahaemolyticus.
AB  - Vibrio parahaemolyticus, a universal marine pathogen with available genome
      sequences, could be used as a bacterial model to clarify the various
      physiological phenomena of its native and host environments. In the present
      study, proteomic methodologies were applied to investigate the expression pattern
      of outer membrane proteins (OMPs) of V. parahaemolyticus at different NaCl
      concentrations. OmpW, OmpV, elongation factor TU and polar flagellin were
      determined to be osmoregulation-sensitive OMPs, among which OmpW and OmpV were
      reported to vary with changed NaCl concentrations in the pattern of osmolarity
      regulation. Therefore, our results not only expand our knowledge on
      osmoregulation-related proteins, but also provide a valuable strategy for the
      screening of salt-sensitive proteins.

PMID- 15567279
TI  - Plasmid-related beta-lactamase production in Bacteroides fragilis strains.
AB  - Twenty Bacteroides fragilis group species isolated from children with and without
      diarrhea were analyzed. Antibiotic susceptibility was performed using an agar
      dilution method; beta-lactamase production was determined using a nitrocefin
      method, and plasmids were extracted using a commercial Miniprep System. MIC
      values ranged from 16 to 256 microg/ml for penicillin, 4-128 microg/ml for
      amoxicillin/clavulanic acid, 0.25-256 microg/ml for clindamycin, and 16-256
      microg/ml for penicillin. beta-Lactamase was detected in all isolates. Only five
      isolates harbored plasmids varying from 7.8 to 1.8 kb. Loss of 6.4- and 3.8-kb
      plasmids in B. fragilis C68c was related to antibiotic resistance. Low molecular
      weight plasmids of 2.8-1.8 kb were stable. PCR amplification of cfiA and cepA
      genes was observed using total DNA, and the cfiA gene was also amplified from the
      6.4-kb plasmid.

PMID- 15567280
TI  - Lactovum miscens gen. nov., sp. nov., an aerotolerant, psychrotolerant, mixed
      fermentative anaerobe from acidic forest soil.
AB  - An aerotolerant, psychrotolerant anaerobe, anNAG3, was isolated from an acidic
      forest floor solution (in situ pH of 4.5). Cells of anNAG3 stained Gram-positive
      did not form spores, and were not motile. Cells were ovoid, approximately 1
      microm long and 0.7 microm wide, mostly in pairs, and contained a multi-layered
      cell wall and intracytoplasmic membranes. Growth was observed at pH 3.5-7.5 and 0
      35 degrees C. Glucose, galactose, fructose, mannitol, glucosamine, N
      acetylglucosamine, cellobiose, and maltose supported growth. Lactate, ethanol,
      formate, and acetate were end products. H(2) and CH(4) were not detected, and
      only very minor amounts of CO(2) were produced. The relative amount of a
      particular product was dependent on the substrate utilized, and product profiles
      indicated that (i) sugars were initially metabolized to pyruvate via glycolysis,
      and (ii) lactate dehydrogenase and pyruvate-formate lyase were responsible for
      the subsequent metabolism of pyruvate. O(2) was not significantly utilized and
      was not toxic to growth. anNAG3 did not contain detectable membranous or
      cytoplasmic cytochromes. Nitrate, sulfate, and Fe(III) were not dissimilated.
      Thus, anNAG3 was characterized as an aerotolerant, non-acetogenic
      chemoorganotroph with a mixed-fermentative metabolism. The G + C content of the
      DNA was 37.6 mol%. The similarity of the 16S rRNA gene sequence of anNAG3 to that
      of its closest phylogenetic relatives (which were in the genera Lactococcus and
      Streptococcus) approximated 88-89%, indicating that anNAG3 constitutes the type
      species of a new genus. Based on the collective properties of anNAG3, it is
      proposed that anNAG3 be termed Lactovum miscens.

PMID- 15567281
TI  - The symbiotic defect in a Sinorhizobium meliloti lipopolysaccharide mutant can be
      overcome by expression of other surface polysaccharides.
AB  - In this work we have examined the extent of functional complementation in
      symbiosis among different Sinorhizobium meliloti surface polysaccharides
      including lipopolysaccharide (LPS). We show that a symbiotic deficiency
      associated with an LPS defect can be reversed by appropriate expression of other
      surface polysaccharides such as galactoglucan (EPSII) and a particular form of
      capsular polysaccharide (KdoPS). It is noteworthy that, while succinoglycan EPSI
      and LPS cannot functionally substitute for each other, they can both be replaced
      by the same common set of polysaccharides (i.e., EPSII/KdoPS). The complex
      pattern of functional complementation in symbiosis among S. meliloti surface
      polysaccharides was shown to be different in Medicago truncatula compared to that
      previously reported for M. sativa.

PMID- 15567282
TI  - Effects of temperature and incubation time on production of ochratoxin A by black
      aspergilli.
AB  - The effects of temperature (5-45 degrees C) on the growth and production of
      ochratoxin A (OTA) by eighteen strains of Aspergillus section Nigri, cultured on
      Czapek yeast autolysate agar (CYA) and on yeast extract sucrose agar (YES), were
      studied for an incubation period of 30 days. Isolates were selected to include
      different sources and different reported abilities to produce OTA. Temperature
      ranges for OTA production were more restrictive than those for growth and each
      strain tested differed in its optimum conditions for OTA production. Aspergillus
      niger aggregate strains achieved maximum OTA levels in YES medium mainly at 20-25
      degrees C. The A. carbonarius strains produced the highest OTA levels in CYA
      medium at 15 or 20 degrees C. Significant amounts of OTA were produced after only
      five days of incubation. Due to their ability to produce OTA at a wide range of
      temperatures, OTA can be continuously produced in the field. This fact has to be
      taken into account in commodities such as grapes, raisins and wine, where A.
      carbonarius and members of the A. niger aggregate are considered to be the main
      sources of the OTA contamination.

PMID- 15567283
TI  - Functional consequences of 7TM receptor dimerization.
AB  - 7TM receptors work as signaling platforms that activate multiple signalling
      systems at the intracellular face of the plasma membrane. It is an emerging
      concept that 7TM receptors form homo- and hetero-dimers or -oligomers in vitro
      and in vivo. Numerous studies suggest dimerization is important for receptor
      function including agonist/antagonist affinity, efficacy, trafficking, and
      specificity of signal transduction, yet it remains unknown whether dimerization
      is a prerequisite for 7TM receptor signaling. The current review provides an
      overview of the biochemical support for 7TM homodimerization, followed by a
      discussion of the characteristics of homodimerization, with focus on dimer
      organization, and the functional consequences of dimerization. Heterodimerization
      will not generally be discussed in this review although we have included a few
      examples to illustrate specific points, and a table that summarises the current
      literature on this subject.

PMID- 15567284
TI  - Acyclovir prodrug for the intestinal di/tri-peptide transporter PEPT1: comparison
      of in vivo bioavailability in rats and transport in Caco-2 cells.
AB  - It has previously been shown that the prodrug Glu(acyclovir)-Sar has a high
      affinity for PEPT1 in Caco-2 cells. However, affinity does not necessarily lead
      to translocation by the transporter which is necessary for achieving an increased
      oral bioavailability. Therefore i.v. and p.o. doses of Glu(acyclovir)-Sar,
      acyclovir and valacyclovir were given to rats and the collected blood samples
      were analysed via LC-MS-MS. Furthermore, Caco-2 cell monolayers were exposed
      apically to Glu(acyclovir)-Sar, acyclovir, and valacyclovir and the concentration
      of drug and prodrugs in the cell extracts were determined and taken as a measure
      for intracellular accumulation. In addition, bi-directional transport studies of
      Glu(acyclovir)-Sar across Caco-2 cell monolayers and in vitro metabolism studies
      of Glu(acyclovir)-Sar in various media of rat origin were performed. For these
      purposes HPLC-UV analysis was applied. Oral administration of Glu(acyclovir)-Sar
      to rats resulted in low bioavailabilities of acyclovir (<2%) and intact prodrug
      (<5%). Studies performed on Caco-2 cell monolayers showed that in contrast to
      valacyclovir Glu(acyclovir)-Sar did not result in a detectable amount of
      acyclovir or Glu(acyclovir)-Sar in the cell extracts. Bi-directional flux across
      Caco-2 cell monolayers apical to basolateral (FluxA-->B) and basolateral to
      apical (FluxB-->A) was measured and the FluxB-->A/FluxA-->B ratios of
      approximately 0.8 indicate that apical efflux mechanisms may not explain this
      lack of intracellular accumulation. These data indicate that Glu(acyclovir)-Sar
      may not be translocated by PEPT1.

PMID- 15567285
TI  - Development of a novel approach towards predicting the milling behaviour of
      pharmaceutical powders.
AB  - A novel approach has been developed for evaluating the milling behaviour of
      pharmaceutical powders based on their material and mechanical properties obtained
      by single particle impact testing. Milling behaviour of two widely used
      pharmaceutical excipients, namely microcrystalline cellulose and alpha-lactose
      monohydrate has been analysed in an oscillatory single ball mill. It is found
      that the milling behaviour of these two powders can be described by analogy with
      a first-order rate process except for alphaLM at 18Hz of milling frequency. At
      the same time, single particle impact testing has been used to infer the material
      properties that are related to breakage. The milling rate of these powders is
      found to correlate well with the parameter representing the material properties
      including the particle size, density, hardness and critical stress intensity
      factor. This provides the basis for a novel approach towards analyzing the
      milling behaviour of a material based on a simple and reliable approach.

PMID- 15567286
TI  - N4-alkyloxycarbonyl derivatives of cytosine: physicochemical characterisation,
      and cytosine regeneration rates and release from alginic acid gels.
AB  - Nucleobase containing compounds might constitute a potential alternative to
      conventional antibiotics in the treatment of Helicobacter pylori infections. N4
      alkyloxycarbonyl-cytosine derivatives were synthesized and subjected to basic
      physicochemical characterisation including assessment of hydrolytic stability in
      various matrices. pH-rate profiles of selected compounds (range 0-12) were
      constructed. Hydrolysis of the derivatives in slightly alkaline solution (60
      degrees C) resulted in quantitative conversion to parent cytosine whereas at
      acidic pH (60 degrees C) liberation of cytosine was in most cases accompanied by
      the parallel formation of uracil. Interestingly the lipophilic N4
      adamantyloxycarbonyl-cytosine prodrug exhibited a half-life of 41 min (pH 1.1 at
      37 degrees C) with quantitative conversion to parent cytosine, the degradation
      rate being approximately 200 times faster than that of the non-cyclic aliphatic
      derivatives investigated. The presence of pig stomach homogenates, pepsin A and
      H. pylori did not have a noteworthy catalytic effect on the hydrolysis of the
      derivatives. The release of parent cytosine was markedly delayed from alginic
      acid gels loaded with the acid-labile and poorly soluble ADC prodrug as compared
      to gels loaded with parent cytosine.

PMID- 15567287
TI  - Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system
      with menthol.
AB  - To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with
      menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous
      solubility of ibuprofen were investigated. The physicochemical properties such as
      gelation temperature, gel strength and bioadhesive force of various formulations
      composed of ibuprofen, menthol and P 188 were investigated. Then, the
      pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed
      of P 188 and menthol were then performed. In the absence of P 188, the solubility
      of ibuprofen increased until the ratio of menthol to ibuprofen increased from
      0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6,
      indicating that four parts of ibuprofen formed eutectic mixture with six parts of
      menthol. In the presence of P 188, the solutions with the same ratio showed
      abrupt increase in the solubility of ibuprofen. Furthermore, the solution with
      ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of
      ibuprofen compared with that without additives and that without menthol,
      respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher
      than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml.
      Ibuprofen increased the gelation temperature and weakened the gel strength and
      bioadhesive force of liquid suppositories. However, menthol did the opposite due
      to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid
      suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen
      solubility of 1.2mg/ml was administered easily to the anus and to remain at the
      administered site without leakage after the dose. Furthermore, it gave
      significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen
      than did solid suppository, indicating that the drug from poloxamer gel could be
      more absorbed than that from solid one in rats. Thus, the liquid suppository
      system with P 188 and menthol, a more convenient and effective rectal dosage form
      for ibuprofen will be expected to enhance the rectal bioavailability of
      ibuprofen.

PMID- 15567288
TI  - Development and validation of a direct, non-destructive quantitative method for
      medroxyprogesterone acetate in a pharmaceutical suspension using FT-Raman
      spectroscopy.
AB  - A simple linear regression method was developed and statistically validated for
      the direct and non-destructive quantitative analysis--without sample preparation-
      of the active pharmaceutical ingredient (API) medroxyprogesterone acetate (MPA)
      in an aqueous pharmaceutical suspension (150 mg in 1.0 ml) using FT-Raman
      spectroscopy. The linear regression was modelled by plotting the highest peak
      intensity of the vector normalized spectral band between 1630 and 1590 cm-1
      against different MPA standard suspension concentrations. At this band, no
      spectral interferences from additives in the suspension are observed. The
      validated model was used for the quantification of a commercial suspension (150
      mg in 1.0 ml) of the commercialized preparations. The same standards and samples
      were used, respectively, for the development and validation of a simple linear
      regression model and for the quantitative determination by means of HPLC-with
      sample preparation-as described for the related substances of MPA in the Ph. Eur.
      IV. The quantification results obtained by the FT-Raman method corresponded with
      the claimed label concentration (150.01+/-0.96 mg/ml (n=6)). Applying the HPLC
      method, however, a systematic error was observed (157.77+/-0.94 mg/ml (n=6)). The
      direct FT-Raman method hence appears the most reliable for the quantification of
      the MPA component in suspension, compared to the HPLC method that requires sample
      preparation. The latter method provides a systematic error because the exact
      volume or density of a suspension sample is unknown. A precise isolation of fixed
      volumes from a suspension is rather unfeasible because of the continuous sagging
      of the suspended particles and their sticking to the used materials in the
      isolation process.

PMID- 15567289
TI  - New optimized piperamide analogues with potent in vivo hypotensive properties.
AB  - We describe herein the structural optimization of new piperamide analogues,
      designed from two natural prototypes, piperine 1 and piperdardine 2, obtained
      from Piper tuberculatum Jacq. (Piperaceae). Molecular modeling studies using
      semiempirical AM1 method were made in order to establish rational modifications
      to optimize them by molecular simplification. The targeted compounds (10) and
      (11) were respectively obtained using benzaldehyde (12) and para-anisaldehyde
      (13) as starting materials. 1H NMR spectra showed that the target compounds were
      diastereoselectively obtained as the (E)-isomer, the same geometry of the natural
      prototypes. These new synthetic amides presented significant hypotensive effects
      in cardiovascular essays using in vivo methodologies. Compound 11 (N-[5-(4'
      methoxyphenyl)-2(E)-pentenoyl]thiomorpholine) showed a potency 10,000 times
      greater than its prototype 5, evidencing an optimization of the molecular
      architecture for this class of hypotensive drug candidates.

PMID- 15567290
TI  - Electrochemical and calorimetric study of oligonucleotide complexation with
      cetylpyridinium chloride.
AB  - The complexation of oligonucleotides and antisense drugs with a cationic
      surfactant, cetylpyridinium chloride (CPC), has been studied using
      electrochemistry at a micrometer sized liquid/liquid interface. This method can
      be used to investigate the effect of chemical and structural modifications on the
      complexation behaviour of oligonucleotides. For the interaction between CPC and
      oligonucleotides the effect of phosphorothioate derivatisation upon binding
      characteristics has been examined. Phosphoromonothioate modification causes the
      onset of binding to occur at a lower free surfactant concentration. Calorimetric
      studies show that surfactants are strongly bound to oligonucleotides and the
      binding is driven by entropy. The enthalpy change for the formation of
      oligonucleotide-surfactant complex is negative in all cases at 25 degrees C
      indicating exothermic reaction.

PMID- 15567291
TI  - Improvement of warfarin biopharmaceutics by conjugation with poly(ethylene
      glycol).
AB  - One of the most used and useful polymers, poly(ethylene glycol) (PEG) was used as
      a carrier for warfarin. The drug-polymer conjugate was freely water soluble at
      room temperature. The hydrolytic stability of the PEG-warfarin was investigated
      at physiological pH and confirmed the stability of the conjugate. In vivo release
      studies demonstrated a good release of parent drug, without the initial high
      plasma level of warfarin.

PMID- 15567292
TI  - Localisation of drug permeability along the rat small intestine, using markers of
      the paracellular, transcellular and some transporter routes.
AB  - The small intestine is the major site of drug absorption. Some reports in the
      literature have evoked the concept of "absorption windows" in the small
      intestine: are there specific regions where drug absorption is significantly
      higher than others? To investigate this question, we used an everted gut sac
      method to study the permeability of drugs and markers every 3-4cm down the entire
      small intestine in rat. These markers were chosen to be representative of the
      mechanisms by which drugs cross the small intestinal mucosa: paracellular and
      transcellular passive diffusion, via influx transporters, and a drug (digoxin)
      that is effluxed from cells by P-glycoprotein (P-gp). The passive diffusion and
      influx transporter markers gave similar profiles with a plateau of permeability
      along the jejunum, and with the exception of L-Dopa, lower permeability in the
      ileum. Digoxin showed a linear decrease in the profile from the proximal jejunum
      to the ileum. Permeability in the duodenum was two to three times lower than the
      jejunum for all compounds. There were no narrow specific regions of high
      permeability and so the concept of discrete "absorption windows" along the small
      intestine as suggested from some pharmacokinetic studies may be related to other
      effects such as pH and/or solubility.

PMID- 15567293
TI  - A novel method for coupling doxorubicin to lactosaminated human albumin by an
      acid sensitive hydrazone bond: synthesis, characterization and preliminary
      biological properties of the conjugate.
AB  - The expression of the asialoglycoprotein receptor on the cells of the large
      majority of the well differentiated hepatocellular carcinomas can be exploited to
      improve the chemotherapy of these tumours by coupling anticancer agents to
      macromolecules taken up by the receptor. In line with this approach, in previous
      experiments we coupled doxorubicin (DOXO) to lactosaminated human albumin (L-HSA)
      using the (6-maleimidocaproyl)hydrazone derivative of the drug as an acid
      sensitive linker. Encouraging results were obtained in laboratory animals using L
      HSA-DOXO. This conjugate, however, has the disadvantage of a difficult synthesis,
      which requires protein thiolation with iminothiolane and can hinder its
      preparation on a large scale. Here we describe a very simple method of coupling.
      The HS-groups required for the reaction with the maleimide moiety of DOXO-EMCH
      are made available in L-HSA by a cleavage of the protein disulphides achieved
      with tris(2-carboxyethyl) phosphine (TCEP). Contrary to thiolic reducing agents,
      the use of TCEP eliminates the need of an inert atmosphere and allows a one-step
      coupling reaction, without purification of the reduced protein before the
      addition of DOXO-EMCH. As the previous L-HSA-DOXO conjugate, the new conjugate
      accomplishes a very efficient liver targeting of the drug. This novel method of
      synthesis should facilitate the preparation of L-HSA-DOXO in the amounts required
      for clinical studies.

PMID- 15567295
TI  - In vitro adsorption of plasma proteins onto the surface (charges) modified
      submicron emulsions for intravenous administration.
AB  - Surface (charge) modified submicron emulsions (cationic and anionic) were
      prepared following the well established combined emulsification techniques and
      characterized for their droplet size distribution and surface charge. The effect
      of these emulsions on in vitro adsorption of plasma proteins was investigated by
      means of two dimensional polyacrylamide gel electrophoresis (2D PAGE). The
      presence of poloxamer 188 in tested emulsions effectively eliminated the
      adsorption of the larger proteins like immunoglobulins, fibrinogen, etc. However,
      depending on the type of surface charges, the smaller proteins such as
      apolipoproteins and albumin were almost completely adsorbed onto the submicron
      emulsions. Indeed, when compared to marketed lipofundin MCT 10%-and deoxycholic
      acid-based anionic emulsions, the adsorption of apolipoprotein, especially apoA
      1, was approximately three times more on stearylamine-and oleylamine-based
      cationic emulsions and oleic acid-based anionic emulsions. In addition, the ratio
      between the apoA-1 and apoA-IV was found to be 1 for lipofundin MCT 10% whereas
      it was about 0.26 for deoxycholic acid-based anionic emulsion and above 5 for
      oleic acid-based anionic emulsions and cationic emulsions. This indicates that
      emulsions having similar surface/interfacial charge imparted by different anion
      forming stabilizers (oleic or deoxycholic acids) exhibited markedly different
      protein adsorption patterns.

PMID- 15567296
TI  - Evaluation of extrusion/spheronisation, layering and compaction for the
      preparation of an oral, multi-particulate formulation of viable, hIL-10 producing
      Lactococcus lactis.
AB  - Three formulation techniques were compared in order to develop a multi
      particulate formulation of viable, interleukin-10 producing Lactococcus lactis
      Thy12. First, freeze-dried L. lactis was compacted into mini-tablets. Next,
      liquid L. lactis culture was used as the granulation fluid for the production of
      pellets by extrusion/spheronisation. Finally, liquid L. lactis culture was
      layered on inert pellets as an alternative technique for the production of
      pellets. L. lactis viability and interleukin-10 production was evaluated.
      Viability dropped to 15.7% after compaction of freeze-dried L. lactis and to 1.0%
      after pelletisation of liquid L. lactis by extrusion/spheronisation. The
      viability in the mini-tablets and pellets, stored for 1 week at RT and 10% RH was
      reduced to 23 and 0.5% of initial viability, respectively. Storage for 1 week at
      RT and 60% RH resulted in complete loss of viability. Layering of L. lactis on
      inert pellets resulted in low viability (4.86%), but 1 week after storage at RT
      and 10% RH, 68% of initial viability was maintained. Increasing product
      temperature and cell density of L. lactis in the layering suspension did not
      significantly change viability after layering and storage. Interleukin-10
      production capacity of L. lactis Thy12 was maintained after layering.

PMID- 15567297
TI  - Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2:
      analysis of affinity constants and comparison with PEPT1.
AB  - The activity of the renal peptide transporters PEPT2 and PEPT1 determines-among
      other factors such as metabolic stability in liver and plasma-the circulatory
      half-life of penicillins and cephalosporins during therapy. This study was
      initiated to examine systematically the interaction of beta-lactam antibiotics
      with PEPT2. Interaction of 31 cephalosporins and penicillins with the carrier
      protein was characterized by measuring their ability to inhibit the uptake of
      [(14)C]Gly-Sar into renal SKPT cells. Cefadroxil, cefaclor, cyclacillin,
      cephradine, cephalexin and moxalactam were recognized by PEPT2 with very high
      affinity comparable to that of natural dipeptides (K(i)=3-100microM). Ceftibuten,
      dicloxacillin, amoxicillin, metampicillin, cloxacillin, ampicillin, cefixime,
      cefamandole, oxacillin and cefmetazole interacted with PEPT2 with medium affinity
      (K(i)=0.1-5mM). For the other beta-lactam antibiotics studied interaction was
      very low or not measurable (K(i)>5mM). The affinity constants of beta-lactam
      antibiotics at rPEPT2 and hPEPT1 are significantly correlated, but the rank
      orders are not identical. Decisive differences between PEPT1 and PEPT2
      recognition of the N-terminal part of the compounds became evident. Moreover,
      this large data set of affinity constants of beta-lactam antibiotics will be
      useful for structure-transport (binding) analyses of PEPT2.

PMID- 15567298
TI  - Formulation development of inhalation powders for FK888 using the E-haler to
      improve the inhalation performance at a high dose, and its absorption in healthy
      volunteers.
AB  - FK888 is a candidate selective NK1 receptor antagonist, and it exhibits poor
      absorption from the gastrointestinal tract in healthy volunteers. In a previous
      study, the optimized dry powder inhaler (DPI) formulation with carrier lactose
      using the Spinhaler was developed, although the maximum dose per capsule was only
      5mg because the fine particle fraction (FPF) was reduced at doses over 5mg. The
      objective of this study was to develop an optimized DPI formulation for higher
      doses, such as 40 mg, with proportional systemic absorption. The Spinhaler and E
      haler were used as the inhalation devices, and the in vitro deposition was
      evaluated using a multistage cascade impactor at different flow rates (28.3 and
      60 l/min). When hydroxypropyl methylcellulose (HPMC) capsules were used as the
      container, and spherical soft agglomerates of fine FK888 particles (soft pellets)
      and the E-haler were used, the fraction of particles emitted from the inhalation
      system (Em) was significantly improved, to over 80% of the nominal dose, and no
      significant difference was found between the airflow rates (84.3+/-2.3% for 28.3
      l/min, 88.1+/-3.6% for 60 l/min). It was also found that the E-haler was an
      extremely suitable device for obtaining the higher respirable particle percentage
      of emitted particles (RP) in the 40 mg formulation with the soft pellets
      contained in HPMC capsules (35.0+/-1.8% for 28.3 l/min and 42.5+/-3.5% for 60
      l/min), compared with the Spinhaler (13.8+/-3.0% for 28.3 l/min and 28.9+/-1.0%
      for 60 l/min). Using the formulations with the E-haler, proportional systemic
      absorption was achieved up to 40 mg FK888 in healthy volunteers (62.91+/-27.58,
      103.70+/-40.19 and 254.79+/-85.01 ngh/ml as AUCs for 10, 20 and 40 mg FK888,
      respectively; R(2)=0.9641). It is also expected that the E-haler will act as an
      efficient device when a higher dose, such as 40 mg, is required in clinical
      situations.

PMID- 15567299
TI  - Large-scale production of lipoplexes with long shelf-life.
AB  - The instability of lipoplex formulations is a major obstacle to overcome before
      their commercial application in gene therapy. In this study, a continuous mixing
      technique for the large-scale preparation of lipoplexes followed by
      lyophilisation for increased stability and shelf-life has been developed.
      Lipoplexes were analysed for transfection efficiency and cytotoxicity in human
      aorta smooth muscle cells (HASMC) and a rat smooth muscle cell line (A-10 SMC).
      Homogeneity of lipid/DNA-products was investigated by photon correlation
      spectroscopy (PCS) and cryotransmission electron microscopy (cryo-TEM). Studies
      have been undertaken with DAC-30, a composition of 3beta-[N-(N,N'
      dimethylaminoethane)-carbamoyl]-cholesterol (DAC-Chol) and
      dioleylphosphatidylethanolamine (DOPE) and a green fluorescent protein (GFP)
      expressing marker plasmid. A continuous mixing technique was compared to the
      small-scale preparation of lipoplexes by pipetting. Individual steps of the
      continuous mixing process were evaluated in order to optimise the manufacturing
      technique: lipid/plasmid ratio, composition of transfection medium, pre-treatment
      of the lipid, size of the mixing device, mixing procedure and the influence of
      the lyophilisation process. It could be shown that the method developed for
      production of lipoplexes on a large scale under sterile conditions led to
      lipoplexes with good transfection efficiencies combined with low cytotoxicity,
      improved characteristics and long shelf-life.

PMID- 15567300
TI  - Permeability modulation of human intestinal Caco-2 cell monolayers by
      interferons.
AB  - We investigated the effects of interferon-beta (IFN-beta) and IFN-gamma on the
      drug efflux activity of the human intestinal Caco-2 cell line, expressing the P
      glycoprotein (P-gp) on the apical membrane. The cells grown on Transwell plates
      were pretreated with 1000U/ml IFN-beta, IFN-gamma or a combination of both for 3
      days, and then the transepithelial electrical resistance (TEER) and the vectorial
      transport of rhodamine-123 (Rho-123) across the cell monolayers were evaluated.
      Exposure to IFN-gamma reduced substantially the TEER, but the effect of IFN-beta
      was minimal? The apparent permeability of Rho-123 in both the basolateral-to
      apical and apical-to-basolateral directions was significantly increased by IFN
      gamma but scarcely by IFN-beta. The combination of IFN-gamma and IFN-beta showed
      similar effects to IFN-gamma alone. Meanwhile, the cellular uptake of Rho-123
      from the apical side was not affected by any IFN treatment. The uptake level was
      increased approximately three times in the presence of verapamil, a P-gp
      inhibitor, and the increased level was not affected by any IFN treatment,
      indicating that the efflux activity mediated by P-gp in the monolayers is not
      altered by these cytokines. Taken together, these results suggest that IFNs
      modulate the permeability of Caco-2 monolayer through effect on paracellular
      transport rather than effect on P-gp activity.

PMID- 15567301
TI  - Conversion of cyclosporine A prodrugs in human tears vs rabbits tears.
AB  - The aim of this study was to evaluate the rate and mechanism of conversion of two
      water-soluble prodrugs of cyclosporine A (CsA) intended for topical delivery to
      the eye. The new molecules were designed according to the double prodrug concept:
      a solubilizing moiety was grafted onto CsA via an ester function, which could be
      hydrolysed via a two-step process (enzymatic and chemical). Prodrug solutions
      were prepared extemporaneously in an isotonic and neutral aqueous medium
      compatible with ophthalmic use. The rates of conversion into the parent molecule
      were determined by incubating the prodrugs in fresh rabbit or human tears or in a
      phosphate buffer solution (PBS) at pH 7.4. Both prodrugs were converted into CsA
      within the first minute in the presence of rabbit tears with rate constants of
      k=5.9x10(-3)min(-1) and k=3.8x10(-3)min(-1), respectively, for UNIL088 and
      UNIL089, whereas chemical conversion in PBS was negligible (k=0.5x10(-3)min(-1)
      for both molecules). Incubation of UNIL088 in human tears showed a significantly
      high conversion rate. It is concluded that the developed double prodrugs
      underwent a bioconversion in physiological media and thus represent promising
      candidates for topical delivery of CsA to the eye.

PMID- 15567302
TI  - Non-phospholipid vesicles for pulmonary glucocorticoid delivery.
AB  - In the formulation of inhaled drugs for the treatment of asthma and chronic
      obstructive pulmonary disease (COPD), considerable attention has been devoted to
      new aerosol morphologies which can either enhance the local effect and/or
      increase the penetration through the mucus, secreted in bronchial inflammatory
      diseases. In diseases characterized by bronchial hypersecretion, lipophilic
      substances, such as corticosteroids, can be remarkably impeded in reaching their
      receptors, which are localized within the cytoplasm of bronchial epithelial
      cells. Vesicles consisting of one or more surfactant bilayers enclosing aqueous
      spaces, are of particular interest because they offer several advantages with
      regard to chemical stability, lower cost and availability of materials compared
      to conventional liposomes. With the purpose of carrying out research leading to
      an innovative formulation for lung delivery capable of permeating the mucous
      layer, beclomethasone dipropionate, clinically used for the treatment of asthma
      and COPD, was entrapped in non-phospholipid vesicles. The composition providing
      the highest entrapment efficiency was chosen. The vesicles obtained after jet
      nebulization were characterized by means of freeze-fracture microscopy and
      dynamic light scattering. The efficiency of this new drug delivery system was
      evaluated in vitro with simulated mucus by means of diffusion experiments (three
      compartment cell apparatus), using 0.1% mucin gel-like dispersion as a barrier to
      drug permeation.

PMID- 15567303
TI  - Applying pattern recognition methods and structure property correlations to
      determine drug carrier potential of nicotinic acid and analogize to
      dihydropyridine.
AB  - Multivariate methods are utilized to compare nicotinic acid and dihydropyridine
      as a drug carrier. Nicotinic acid and dihydropyridine form ester groups on 10
      beta-lactam antibiotics with an oxymethyl group forming a linkage between the
      antibiotic and the drug carrier (nicotinic acid or dihydropyridine). Calculated
      molecular properties are analyzed by self-organizing tree algorithm (SOTA),
      bivariate regression, cluster analysis, factor analysis, discriminant analysis,
      hierarchical classification, and principal coordinates analysis. Ten important
      pharmacological properties for each of the nicotinic acid and dihydropyridine
      antibiotic derivatives are numerically similar and highly correlated. Calculated
      molecular properties include molar refractivity, molar volume, parachor, index of
      refraction, partition coefficient (log P), polarizability, and polar surface
      area. Dermal permeability coefficients (Kp) for nicotinic acid derivatives are
      similar to values for dihydropyridine derivatives. Dermal permeabliity
      coefficients analyzed by hierarchical classification and SOTA analysis were shown
      to be closely interrelated and highly correlated. Ten properties of the nicotinic
      acid and dihydropyridine were compared by Passing-Bablok regression analysis and
      shown to be highly correlated (r=0.9879). Box plot analysis of 10 properties,
      inclusive of both groups of derivatives, showed narrow ranges in values. Cluster
      analysis of derivative properties showed the nicotinic acid derivatives to be
      highly similar to the dihydropyridine derivatives of the same antibiotics.
      Cluster analysis was performed by single linkage, complete linkage, and centroid
      linkage. Factor analysis showed the nicotinic acid derivatives to be interrelated
      and similar to the dihydropyridine derivatives. Discriminant analysis performed
      on all derivatives formed a single highly cohesive and non-differentiated
      cluster, demonstrating strong similarity among nicotinic acid and dihydropyridine
      derivatives. Principal coordinates analysis (determines similarity) of Kp values
      showed high similarity between the nicotinic acid and dihydropyridine antibiotic
      derivatives.

PMID- 15567304
TI  - Drug release from tableted wet granulations comprising cellulosic (HPMC or HPC)
      and hydrophobic component.
AB  - The effects of component nature, proportion and processing on the release rate
      and mechanism were investigated for tablets comprising drug, cellulosic polymer
      and hydrophobic components. Four drugs differing in solubility (diclofenac
      sodium, ibuprofen, naproxen and indomethacin), two cellulosic polymers (HPC and
      HPMC) and hydrophobic Emvelop were used in two levels of mass fraction and weight
      ratio of drug:carrier and of cellulosic-hydrophobic component. Compression was
      applied after granulation or physical mixing. Drug release was evaluated in pH
      6.5 phosphate buffer BP and elucidation of the release mechanism was attempted by
      fitting kinetic models. Statistical significance of the effects of formulation
      variables on the release rate and mechanism expressed by the coefficient, k, and
      exponent, n, of the power law kinetic model, respectively, was evaluated by
      ANOVA. It was found that for the release mechanism most significant is the effect
      of drug solubility followed by cellulosic polymer type, mixing procedure and drug
      mass fraction. Significant interaction between drug solubility and type of
      cellulosic polymer indicated that alteration in the swelling of HPMC and HPC is
      caused by the drug solubility. Weight ratio of cellulosic-hydrophobic component
      does not affect the release mechanism, but only the release rate. Similarly, for
      the release rate most significant was found the effect of drug solubility,
      followed by cellulosic polymer type, weight ratio of cellulosic-hydrophobic
      component, mixing method and drug mass fraction. Also significant were the
      interactions of drug solubility with the type and proportion of the cellulosic
      polymer and the processing applied. Depending on the drug solubility and type of
      polymer present, wet granulation can increase or decrease the release rate.

PMID- 15567305
TI  - Properties of hot-melt extruded tablet formulations for the colonic delivery of 5
      aminosalicylic acid.
AB  - Hot-melt extruded tablets were prepared using Eudragit S 100 as the polymeric
      carrier to target delivery of 5-aminosalicylic acid (5-ASA) to the colon.
      Scanning electron microscopy, modulated differential scanning calorimetry and X
      ray diffraction analysis of the hot-melt tablet extrudates demonstrated that 5
      ASA remained crystalline and was homogeneously dispersed throughout the polymer
      matrix. A pre-plasticization step was necessary when incorporating triethyl
      citrate (TEC) into the formulation in order to achieve uniform mixing of the
      polymer and plasticizer, effectively reduce the polymer glass transition
      temperature (T(g)), and to lower the processing temperatures. The concentration
      of TEC in the extrudates not only influenced the processing temperature, but also
      influenced the drug release rates from the extruded tablets due to leaching of
      the TEC during dissolution testing. Citric acid monohydrate was found to
      plasticize Eudragit S 100, and when combined with TEC in the powder blend, the
      temperatures required for processing were reduced. Tablets containing citric acid
      released drug at a slower rate as a result of the suppression of polymer
      ionization due to a decrease in the micro-environmental pH of the tablet. The
      drug release profiles of the extruded tablets were found to fit both diffusion
      and surface erosion models.

PMID- 15567306
TI  - Solid-state characterization and dissolution properties of naproxen-arginine
      hydroxypropyl-beta-cyclodextrin ternary system.
AB  - The effect of ternary complexation of naproxen, a poorly water soluble anti
      inflammatory drug, with hydroxypropyl-beta-cyclodextrin and the basic aminoacid L
      arginine on the drug dissolution properties has been investigated. Equimolar
      binary (drug-cyclodextrin or drug-arginine) and ternary (drug-cyclodextrin
      arginine) systems were prepared by blending, cogrinding, coevaporation, and
      characterized by differential scanning calorimetry, thermogravimetric analysis,
      FT-IR spectroscopy, X-ray diffractometry. The dissolution behavior of naproxen
      from the different products was evaluated by means of a continuous flow through
      method. The results of solid state studies indicated the presence of strong
      interactions between the components in ternary coevaporated and coground systems,
      which were both of totally amorphous nature. In contrast, the presence of either
      free drug or free arginine was detected when the third component (cyclodextrin or
      aminoacid) was physically mixed, respectively, to the drug-arginine binary system
      (as physical mixture, coevaporate, or coground product) or to the drug
      cyclodextrin binary system (as physical mixture, coevaporate, or coground
      product). All ternary combinations were significantly (P<0.001) more effective
      than the corresponding binary drug-cyclodextrin and drug-arginine systems in
      improving the naproxen dissolution rate. The best performance in this respect was
      given by the ternary coevaporate, with about 15 times increase in terms of both
      drug relative dissolution rate and dissolution efficiency. The synergistic effect
      of the simultaneous use of arginine and cyclodextrin on the dissolution rate of
      naproxen was attributed to the combined effects of inclusion in cyclodextrin and
      salt formation, as well as to a specific role played by arginine in this
      interaction.

PMID- 15567307
TI  - Solid dispersions of nimodipine and polyethylene glycol 2000: dissolution
      properties and physico-chemical characterisation.
AB  - The incorporation of a drug in a carrier by melt embedding may either result in a
      solid solution or in a solid suspension of the active ingredient within the
      carrier material. As the dispersivity of the drug is of outstanding importance
      for its dissolution characteristics, parameters which are supposed to influence
      crystallinity and dispersivity, e.g. cooling rate during preparation and storage
      conditions like temperature and relative humidity are investigated. It is found
      that the absence of crystalline drug material in solid dispersions containing
      nimodipine and polyethylene glycol 2000 is the prerequisite for a high
      dissolution rate and a remarkable supersaturation in the dissolution medium.
      Shock freezing during the preparation process, low storage temperatures and low
      relative humidities are identified to prevent recrystallisation. Furthermore,
      emphasis is put on the physico-chemical characterisation of solid dispersions. It
      is shown that the determination of crystallinity and dispersivity of the drug in
      solid dispersions can only be successful by combining different investigation
      methods like differential scanning calorimetry, hot stage microscopy, X-ray
      diffraction as well as macroscopic observation.

PMID- 15567308
TI  - Study of the physicochemical properties and stability of solid dispersions of
      loperamide and PEG6000 prepared by spray drying.
AB  - Solid dispersions of PEG6000 and loperamide-a poorly water-soluble agent-were
      prepared by spray drying. Their physicochemical properties were evaluated
      immediately after preparation. The dissolution was higher than that of pure
      crystalline loperamide. DSC- and XRD-measurements revealed that in the
      dispersions, loperamide is partially present in the crystalline state. A eutectic
      state diagram was obtained. The samples containing 20% loperamide were stored
      under different conditions (40 degrees C and 0% RH, 25 degrees C and 52% RH, 4
      degrees C and 0% RH) to investigate their stability as a function of time. The
      dissolution properties deteriorate upon storage at high temperature (40 degrees C
      and 0% RH) and in conditions of higher relative humidity (25 degrees C and 52%
      RH). The DSC-curves clearly indicate an increase in the amount of crystalline
      compound under these conditions. From these observations it could be concluded
      that loperamide, which is partially crystalline and partially amorphous in the
      freshly prepared samples, continues to crystallize under these conditions,
      resulting in progressively poorer dissolution properties.

PMID- 15567309
TI  - Preliminary assessment of carrageenan as excipient for extrusion/spheronisation.
AB  - The current study pursues the suitability of different types of carrageenan as a
      novel extrusion aid. The aim was to find out a suitable substitution to the
      commonly used microcrystalline cellulose (MCC). The types of kappa-carrageenan
      were found to be the most appropriate material and the required fraction to
      produce acceptable pellets in the formulation was determined. The investigation
      showed that 5% of kappa-carageenan was necessary to produce pellets without MCC.
      Similar formulations produced with MCC or kappa-carrageenan were compared with
      respect to size and shape of the pellets. kappa-Carrageenan required higher water
      content for the formation of pellets, but the formulation was more robust as the
      optimal range of water content was much broader. Hence, kappa-Carrageenan seems
      to be a suitable and promising extrusion aid. The study showed that the
      substitution of MCC by kappa-carrageenan in formulations is possible and the
      produced pellets were of high quality.

PMID- 15567310
TI  - Compaction mechanism and tablet strength of unlubricated and lubricated
      (silicified) microcrystalline cellulose.
AB  - This paper describes the differences in compaction properties between
      microcrystalline cellulose (MCC) and microcrystalline cellulose co-processed with
      colloidal silicon dioxide (SMCC). The different compaction parameters are not
      only compared for the pure materials, but also for the lubricated powders with
      magnesium stearate. Neither magnesium stearate, nor colloidal silicon dioxide,
      facilitates extensively the densification of (silicified) microcrystalline
      cellulose during compaction. The difference in tablet relaxation of MCC and SMCC
      indicates a small negative effect of colloidal silicon dioxide on the
      interparticle bonding strength of unlubricated MCC. However, for lubricated MCC a
      larger increase in tablet relaxation at a high compression speed was found than
      for lubricated SMCC tablets. Accordingly, the decrease in tablet strength was
      larger for the MCC tablets than for the SMCC tablets when lubrication was
      applied. The examination of the tablet strengths of tablets compressed from
      physical mixtures of MCC with increasing concentrations of colloidal silicon
      dioxide proved the slightly negative influence of silicon dioxide on the tablet
      strength of unlubricated MCC tablets and the positive effect of colloidal silicon
      dioxide addition on the tensile strength of lubricated MCC tablets. Co-processing
      of MCC with colloidal silicon dioxide showed no extra contribution on the tablet
      strength of lubricated tablets above the physical mixtures. The interactions
      between the different materials were further supported by the interaction
      parameters based on partial solubility parameters.

PMID- 15567311
TI  - Effects of gamma-irradiation on trehalose-hydroxyethylcellulose microspheres
      loaded with vancomycin.
AB  - Ionizing radiation can be used as a drug sterilization technique, provided that
      the drug itself is not modified and that no toxic products are produced;
      moreover, if the irradiated product is a drug delivery system, the drug release
      characteristics must not be significantly altered by radiation. The aim of this
      work was to study the effects of sterilization by ionizing radiation on
      hydroxyethylcellulose/trehalose spherical micromatrices, containing the
      antibiotic vancomycin. Our experimental results showed that gamma-rays did not
      alter the chromophore groups of vancomycin (UV measurements), and did not modify
      the kinetic behavior of drug release from microspheres. Moreover, no significant
      changes in the shape and in the size distribution of microspheres were found
      after irradiation. The electron spin resonance (ESR) spectroscopy was proven to
      be a valid identification method of the executed radiation treatment, even after
      5 years. The experimental results showed that the therapeutic application of the
      pharmacological system investigated was not compromised by irradiation, and that
      ESR spectroscopy can be used to distinguish irradiated from non-irradiated
      products.

PMID- 15567312
TI  - Influence of hydroxyethylcellulose on the drug release properties of theophylline
      pellets coated with Eudragit RS 30 D.
AB  - The objective of this study was to investigate the influence of a hydrophilic
      polymer, hydroxyethylcellulose (HEC), on the release properties of theophylline
      from pellets coated with Eudragit RS 30 D, and the physicochemical properties of
      Eudragit RS 30 D cast films. The release rate of theophylline from Eudragit RS 30
      D coated pellets decreased during storage at 25 degrees C/60% RH due to the
      further coalescence of colloidal acrylic particles. In addition, water-vapor
      permeability and tensile strength of Eudragit RS 30 D cast film decreased after 1
      month storage at 25 degrees C/60% RH. The presence of 10% hydroxyethylcellulose
      in the coating formulation was shown to stabilize the drug release rate from
      coated pellets, the water-vapor permeability and the tensile strength of free
      films. Atomic force microscopy and scanning electronic microscopy were used to
      demonstrate that the HEC was immiscible with Eudragit RS 30 D in the cast films.
      The stabilization effect of HEC was investigated and determined to be due to the
      formation of an incompatible phase between the latex particles which impaired
      further coalescence of the colloidal acrylic particles.

PMID- 15567313
TI  - Synthesis and properties of polysaccharide prodrugs of 5-aminosalicylic acid as
      potential colon-specific delivery systems.
AB  - The drug release of the polymer prodrugs of 5-aminosalicylic acid (5-ASA) was not
      only dependent on the property of the polymers but also dependent on the
      solubility of the prodrugs. We prepared several polysaccharide prodrugs of 5-ASA
      to examine the effect of solubility of prodrugs on the release characteristics of
      5-ASA in the gastrointestinal contents of rats. The amide prodrug, chitosan-5-ASA
      (ChT-5-ASA), did not release the 5-ASA in the cecal and colonic contents. The
      ester prodrugs, hydroxypropyl cellulose-5-ASA (HPC-5-ASA), being poor solubility
      in 0.05mol/l acetic acid solution also did not release the 5-ASA in any of
      gastrointestinal contents of rats. Whereas the 5-ASA release from cyclodextrins-5
      ASA (CyDs-5-ASA) in cecal and colonic contents was significantly higher than that
      in stomach and small intestine contents. And furthermore, with the decrease in
      the degree of substitution, the solubility of CyD-5-ASA increased, and the
      release of 5-ASA in the gastrointestinal contents was also higher at the same
      time interval of incubation. When the ratio of cyclodextrin (CyD) and 5
      formylaminosalicylic acid (5-fASA), a precursor of 5-ASA prodrugs, was 1:10, CyD
      5-ASA was very slightly soluble, and no release of 5-ASA was observed within 48h
      in gastrointestinal contents. The present results suggested that the ester
      prodrugs of 5-ASA with certain solubility could release 5-ASA in the cecal and
      colonic contents of rat.

PMID- 15567314
TI  - Liposomal incorporation of Artemisia arborescens L. essential oil and in vitro
      antiviral activity.
AB  - The effect of liposomal inclusion on the in vitro antiherpetic activity of
      Artemisia arborescens L. essential oil was investigated. In order to study the
      influence of vesicle structure and composition on the antiviral activity of the
      vesicle-incorporated oil, multilamellar (MLV) and unilamellar (SUV) positively
      charged liposomes were prepared by the film method and sonication. Liposomes were
      obtained from hydrogenated (P90H) and non-hydrogenated (P90) soy
      phosphatidylcholine. Formulations were examined for their stability for over one
      year, monitoring the oil leakage from vesicles and the average size distribution.
      The antiviral activity was studied against Herpes simplex virus type 1 (HSV-1) by
      a quantitative tetrazolium-based colorimetric method. Results showed that
      Artemisia essential oil can be incorporated in good amounts in the prepared
      vesicular dispersions. Stability studies pointed out that vesicle dispersions
      were very stable for at least six months and neither oil leakage nor vesicle size
      alteration occurred during this period. After one year of storage oil retention
      was still good, but vesicle fusion was present. Antiviral assays demonstrated
      that the liposomal incorporation of A. arborescens essential oil enhanced its in
      vitro antiherpetic activity especially when vesicles were made with P90H. On the
      contrary, no significant difference in antiviral activity was observed between
      the free and SUV-incorporated oil.

PMID- 15567315
TI  - Evaluation of in vitro and in vivo antitumor activity of BCNU-loaded PLGA wafer
      against 9L gliosarcoma.
AB  - The purpose of the present study was to develop implantable BCNU-loaded poly(D,L
      lactide-co-glycolide) (PLGA) wafer for the controlled release of 1,3-bis(2
      chloroethyl)-1-nitrosourea (BCNU) and to evaluate its in vitro and in vivo
      antitumor activity. The release rate of BCNU from PLGA wafer increased with the
      increase of BCNU amount loaded and the release was continued until 7 days. In
      vitro and in vivo antitumor activity of BCNU-loaded PLGA wafer was investigated
      using in vitro cytotoxicity against 9L gliosarcoma cells and a subcutaneous
      (s.c.) solid tumor model of 9L gliosarcoma, respectively. The wafers containing
      BCNU showed more effective cytotoxicity than BCNU powder due to its short half
      life and inhibited the proliferation of 9L gliosarcoma cells. BCNU-loaded PLGA
      wafer delayed the growth of the tumors significantly and increasing the dose of
      BCNU in the wafer resulted in a substantial regression of the tumor. These
      results of antitumor activity of BCNU-loaded PLGA wafer demonstrate the
      feasibility of the wafers for clinical application.

PMID- 15567316
TI  - Development and characterization of a novel Cremophor EL free liposome-based
      paclitaxel (LEP-ETU) formulation.
AB  - Taxol is a marketed product for the treatment of ovarian, breast, non-small cell
      lung cancer and AIDS-related Kaposi's Sarcoma. It is thus far one of the most
      effective anticancer drugs available on the market. However, paclitaxel is only
      sparingly soluble in water and therefore, intravenous administration depends on
      the use of the non-ionic surfactant Cremophor EL (polyethoxylated castor oil) to
      achieve a clinically relevant concentrated solution. Unfortunately, Cremophor EL
      increases toxicity and leads to hypersensitivity reactions in certain
      individuals. We have developed a well characterized novel lyophilized liposome
      based paclitaxel (LEP-ETU) formulation that is sterile, stable and easy-to-use.
      The mean particle size of the liposomes is about 150 nm before and after
      lyophilization, and the drug entrapment efficiency is greater than 90%. Stability
      data indicated that the lyophilized LEP-ETU was physically and chemically stable
      for at least 12 months at 2-8 and 25 degrees C. Moreover, the formulation can be
      diluted to about 0.25mg/ml without drug precipitation or change in particle size.
      In vitro drug release study in phosphate-buffered saline (PBS, pH 7.4) showed
      that less than 6% of the entrapped paclitaxel was released after 120 h,
      indicating that the drug is highly stable in an entrapped form at physiologic
      temperature.

PMID- 15567317
TI  - Characterization of cellulosic hot-melt extruded films containing lidocaine.
AB  - Hot-melt extrusion technology was used to produce thin films containing a model
      drug, lidocaine, and the cellulosic polymers hydroxypropyl cellulose (HPC) and
      hydroxypropyl methyl cellulose (HPMC). Two film formulations were extruded and
      compared, one containing only HPC and the other containing HPC:HPMC (80:20).
      Thermal analysis of the films using differential scanning calorimetry (DSC)
      suggested that the drug existed in the amorphous condition, which was confirmed
      by wide angle X-ray diffractometry. Sustained release of the drug was observed
      from both of the polymer matrices. Dissolution profiles suggested that HPMC
      retarded the drug release from HPC:HPMC (80:20) films. However, the mechanism of
      drug release from both of the films was predominantly diffusion of the drug
      through the polymer matrices. Incorporation of HPMC also increased both adhesive
      strength and work of adhesion as compared to the HPC-only films.

PMID- 15567318
TI  - The interaction between carrier rugosity and carrier payload, and its effect on
      drug particle redispersion from adhesive mixtures during inhalation.
AB  - The effectiveness of press-on forces (defined as the adhesive forces between drug
      and carrier particles) in relation to carrier payload as the result of collisions
      between carrier particles during the mixing process of an adhesive mixture, has
      been investigated. Three different carriers of the same size fraction (250-355
      microm), but with completely different surface rugosity were studied. It could be
      shown that this effectiveness depends on the carrier rugosity. The fraction of
      drug detached from the carrier particles during inhalation appeared to decrease
      faster with increasing carrier payload for crystalline carriers than for granular
      carriers. Apparently, increasing the volume of the carrier surface cavities
      increases the drug mass that can find shelter from the press-on forces during
      mixing. By measuring the size distribution in the aerosol, it could also be shown
      that the press-on forces may increase the size of the particles that are
      detached. This seems to be the result of drug particle re-agglomeration on the
      carrier surface during mixing. On the other hand, when press-on forces are highly
      ineffective, an increase in the size of detached particles may also be the result
      of incomplete break-up of natural drug agglomerates. Finally, it could be shown
      that when the press-on forces are highly effective, the effect of mixing time is
      small.

PMID- 15567319
TI  - Mucoadhesive, triclosan-loaded polymer microspheres for application to the oral
      cavity: preparation and controlled release characteristics.
AB  - The aim of this study was to develop mucoadhesive microspheres that can be
      utilised for the controlled release of triclosan in oral-care formulations,
      specifically dental pastes. Using a double-emulsion solvent evaporation
      technique, triclosan was incorporated into microspheres that were prepared from
      Gantreztrade mark MS-955, Carbopol 974P, polycarbophil or chitosan and the
      profiles for its release were established under simulated 'in use' conditions.
      Triclosan was rapidly released into a sodium lauryl sulphate containing buffer
      from all but the chitosan microspheres. The release of triclosan from
      microspheres suspended in a non-aqueous paste, was found to be sustained over
      considerable time-periods, which were influenced strongly by the nature of the
      polymeric carrier. For microspheres that were fabricated from Gantrez, Carbopol
      or polycarbophil, the release appeared to obey zero-order kinetics whereas in the
      case of chitosan-derived vehicles, the release profile fitted the Baker and
      Lonsdale model. The work has demonstrated that these polymeric microspheres,
      particularly those of chitosan, are promising candidates for the sustained
      release of triclosan in the oral cavity.

PMID- 15567320
TI  - Development of a long-acting therapeutic system: Part I: A method to produce
      silicon rubbers with well-defined microstructures.
AB  - Based on the free-volume theory of diffusion in rubbers it is shown that the
      diffusion coefficient D of a permeating drug can be written as the product of two
      probabilities D approximately w(1)w(2). The polymer chains in a rubber are
      subject to thermal vibrations. Hence collisions between vibrating polymer
      segments and permeating drug molecules can occur. w(1) describes the probability
      that by such a collision a drug molecule experiences an energy exchange which is
      large enough to overcome its interactions with its neighborhood. w(2) describes
      the probability that a permeating drug molecule will find in its immediate
      neighborhood a free volume being equal or larger than its own volume. Diffusion
      takes place if the drug molecule experiences a sufficiently large exchange of
      momentum and finds at the same time a sufficiently large free volume. As both
      events are independent their overall probability is given by the product of the
      two probabilities. For a given rubber and a given species of drug molecules in a
      first approximation w(1) can be considered as constant. This means the diffusion
      coefficient is mainly determined by w(2). This probability, however, is strongly
      determined by the microstructure of the rubber. In this study a procedure is
      developed allowing for a straightforward synthesis of silicone rubbers with
      defined network density.

PMID- 15567321
TI  - Handling of computational in vitro/in vivo correlation problems by Microsoft
      Excel: IV. Generalized matrix analysis of linear compartment systems.
AB  - A linear system comprising n compartments is completely defined by the rate
      constants between any of the compartments and the initial condition in which
      compartment(s) the drug is present at the beginning. The generalized solution is
      the time profiles of drug amount in each compartment, described by
      polyexponential equations. Based on standard matrix operations, an Excel
      worksheet computes the rate constants and the coefficients, finally the full time
      profiles for a specified range of time values.

PMID- 15567322
TI  - Reverse iontophoresis of lithium: electrode formulation using a thermoreversible
      polymer.
AB  - This work investigated the use of a thermoreversible gel as a collector vehicle
      in reverse iontophoresis applications. A 20% (w/w) aqueous gel of Pluronic F127
      was a suitable receptor medium to be used at the cathodal chamber. In vitro
      iontophoresis experiments investigated the simultaneous extraction of lithium
      (analyte of interest) and sodium (used as an internal standard) into either a
      control buffer or a gelled receptor. The gelification process at room temperature
      provided a suitable consistency and contact with the skin surface during the
      iontophoresis experiments. Subsequent cooling of the gelled solution to 4 degrees
      C allows an easy recovery of lithium and sodium for later quantification. Both
      the lithium extraction fluxes and the lithium to sodium ratio of extraction
      fluxes were linearly related to the subdermal lithium concentration. On the
      whole, the results show that thermoreversible polymer solutions offer a simple
      and convenient way to handle samples in reverse iontophoresis studies.

PMID- 15567323
TI  - The promise of siRNAs for the treatment of influenza.
AB  - Current WHO reports on the Asian avian influenza virus outbreaks are poignant
      reminders of the potential for the emergence of highly virulent strains of
      influenza A virus (IAV) and the fact that it remains a scourge on human health.
      As IAV drifts and shifts its genetic and antigenic composition, it presents an
      ever-changing challenge for vaccines and antiviral medications. Short-interfering
      RNAs (siRNAs) are the latest class of potential antiviral therapeutics to be
      developed. Recent reports using siRNAs in mice suggest that they hold great
      promise for the prevention and treatment of IAV infections.

PMID- 15567324
TI  - Single cell proteomics for personalised medicine.
AB  - Recently, multicolour FACS combined with phosphospecific antibodies has been
      developed, enabling the determination of the relative phosphorylation of signal
      transduction intermediates in individual cells. It has become clear that, when
      stimulated with cytokines, individual leukemia cells exhibit marked differences
      in phosphoprotein patterns and that these patterns correlate with disease
      outcome. Thus, single cell phosphoproteomic techniques might be superior to other
      proteomic approaches for the molecular diagnosis of disease and instrumental for
      the development of personalised medicine.

PMID- 15567325
TI  - Unexpected Hedgehog-Wnt interactions in epithelial differentiation.
AB  - Wnt and Hedgehog (Hh) signalling regulate stem-cell self-renewal and
      differentiation in a range of epithelia and the inappropriate activation of these
      pathways contributes to epithelial cancers. Recently, it was reported that Indian
      Hedgehog (Ihh) antagonises Wnt signalling in colonic epithelium. This observation
      contrasts with other reports of positive synergy between the pathways and
      challenges the view that systemically administered Hedgehog antagonists could be
      beneficial for the treatment of intestinal tumours. The work is discussed in the
      broader context of Ihh expression and function in epithelia and the different
      ways in which the Hh and Wnt pathways interact.

PMID- 15567326
TI  - Inflammation and apoptosis: linked therapeutic targets in spinal cord injury.
AB  - The secondary cascade of cell death that follows central nervous system (CNS)
      injury or ischemia has long been considered a target for neuroprotective agents
      aimed at sparing tissue and function. Recently, several laboratories have shown
      remarkable protection and recovery of function in rodent models of spinal cord
      injury using treatments that target components of the CNS inflammatory response.
      The use of minocycline, an antibiotic that reduces microglial activation,
      antibody blockade of the CD95 (FAS) ligand and the blockade of glycosphingolipid
      induced iNOS (inducible nitric oxide synthase) have recently been shown to reduce
      neuronal and glial apoptosis with concomitant improvement in neurological
      function, and appear to enhance the efficacy of cell transplantation strategies.

PMID- 15567327
TI  - Molecular mechanisms of water transport in bile formation: aquaporin water
      channels.

PMID- 15567328
TI  - Salivary glands: novel target sites for gene therapeutics.
AB  - Directing the local or systemic expression of therapeutic proteins is a
      potentially important clinical application of gene transfer technology. Gene
      based therapeutics theoretically offer many advantages over protein therapeutics.
      Numerous tissues have been evaluated for this purpose in animal models, most
      commonly the liver and skeletal muscle. Based on pre-clinical studies, we suggest
      that salivary glands are a valuable, yet under-appreciated, target tissue for
      both systemic and upper gastrointestinal tract gene therapeutic applications.

PMID- 15567329
TI  - Targeting promiscuous signaling pathways in cancer: another Notch in the bedpost.
AB  - The chromosomal translocation t(7;9)(q34;q34.3) in human T-cell acute
      lymphoblastic leukemia results in the constitutive activation of Notch (Nic).
      Reported mutations in Ikaros cause the loss of DNA-binding, which in turn leads
      to a loss of repressive activity. Recently, these two mutations have been shown
      to cooperate in leukemogenesis. The current model proposes that the combination
      of the loss of Ikaros activity and the gain of constitutive Notch activity
      disrupts the normal balance between repression and activation at common
      regulatory elements. Furthermore, the model is extended to suggest that multiple
      transcription factors coordinate transcriptional repression and activation
      through these common regulatory elements. In leukemogenesis, the breakdown of
      this coordinate regulation underlies one of the pathophysiological mechanisms.
      Finally, using Notch as a template, potential points of interdiction by designer
      therapeutics are discussed.

PMID- 15567330
TI  - The role of pyocyanin in Pseudomonas aeruginosa infection.
AB  - Pyocyanin (PCN) is a blue redox-active secondary metabolite that is produced by
      Pseudomonas aeruginosa. PCN is readily recovered in large quantities in sputum
      from patients with cystic fibrosis who are infected by P. aeruginosa. Despite in
      vitro studies demonstrating that PCN interferes with multiple cellular functions,
      its importance during clinical infection is uncertain. This is partially caused
      by the difficulty in defining the contribution of PCN among the numerous
      virulence factors produced by P. aeruginosa during infection. In addition, few
      cellular pathways that are affected by PCN are known. This review briefly
      highlights recent advances that might clarify the role of PCN in P. aeruginosa
      pathogenesis.

PMID- 15567331
TI  - Cooperative translational control of gene expression by Ras and Akt in cancer.
AB  - Ras and Akt are signaling proteins that mediate fundamental aspects of normal
      growth and development in many organisms. When the Ras and Akt pathways become
      overly active, malignant transformation of normal tissue can occur. The combined
      activity of these two proteins has generated the transformation of human cell
      cultures and tumor formation in mice. In this review we highlight malignant
      glioma as a tumor type in which Ras and Akt pathways cooperate to cause
      tumorigenesis and regulate translation. The downstream components of these
      pathways have provided therapeutic targets that are currently being tested in
      clinical trials.

PMID- 15567332
TI  - Enhanced tail pinch-induced activation of catecholamine metabolism in the
      pericerulean area of RU 24722-treated rats.
AB  - Our study was devoted to determine in freely moving rats whether the increase in
      tissue concentration of tyrosine hydroxylase (TH) elicited by a single
      administration of RU 24722 could modify the catecholaminergic reactivity of
      neuronal processes present in the rostrolateral part of the pericerulean area (r
      lPCA) in response to tail pinch. Catecholaminergic activity was monitored by
      measuring in vivo the concentration of dopamine metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) using microdialysis coupled to HPLC detection.
      In this study, the microdialysis probe was implanted at a sufficient distance
      from the lateral border of rostral nucleus locus ceruleus (LC) to avoid a large
      contribution of the noradrenergic cell bodies in the measurements performed. We
      first evidenced that DOPAC measured in the r-lPCA indicated the functional state
      of catecholaminergic metabolism in neuronal processes (dendrites and fibers)
      laying in this region. We also showed that the enhancement of TH protein
      concentration in the r-lPCA following RU 24722 treatment supported an increased
      in vivo catecholaminergic metabolism in this region. Furthermore,
      catecholaminergic metabolism response to tail pinch was potentiated in animals
      with greater TH tissue concentration. Thus, our study reveals that the modulation
      of both TH concentration and catecholaminergic metabolism in the r-lPCA may be
      critical in the functioning of cells and neuronal elements present in this
      region, notably in adaptive responses to noxious stimuli.

PMID- 15567333
TI  - In vivo 1H magnetic resonance spectroscopy, T2-weighted and diffusion-weighted
      MRI during lithium-pilocarpine-induced status epilepticus in the rat.
AB  - Temporal lobe epilepsy (TLE) is associated with febrile convulsions and childhood
      status epilepticus (SE). Since the initial precipitating injury, triggering
      epileptogenesis, occurs during this SE, we aimed to examine the metabolic and
      morphological cerebral changes during the acute phase of experimental SE
      noninvasively. In the rat lithium-pilocarpine model of SE, we performed
      quantified T(2)- and isotropic-diffusion-weighted (DW) magnetic resonance imaging
      (MRI) at 3 and 5 h of SE and acquired single-voxel (1)H MR spectra at 2, 4 and 6
      h of SE. T(2) was globally decreased, most pronounced in the amygdala (Am) and
      piriformic cortex (Pi), in which also a significant decrease in apparent
      diffusion coefficient (ADC) was found. In contrast, ADC values increased
      transiently in the hippocampus (HC) and thalamus (Th). MR spectra showed a
      decrease in N-acetylaspartate (NAA) and choline (Cho) and an increase of lactate
      in a hippocampal voxel. The T(2) decrease, attributed to raised deoxyhemoglobin,
      and the presence of lactate both indicate a mismatch between oxygen demand and
      delivery. The ADC decrease, indicative of excitotoxicity, confirms that the
      amygdala and piriformic cortex are particularly vulnerable to lithium-pilocarpine
      induced seizures. The transient ADC increase in the thalamus may reflect the
      breakdown of the blood-brain barrier (BBB), which is shown to occur in this
      region at these time points. Neuronal damage and failure of energy-dependent
      formation of NAA are likely causes of an observed decrease in NAA, while the
      decrease in Cho is possibly due to depletion of the cholinergic system. This
      study illustrates that relative hypoxia, excitotoxicity and concomitant neuronal
      damage associated with SE can be probed noninvasively with MR. These pathological
      phenomena are the first to contribute to the pathophysiology of spontaneous
      recurrent seizures in a later stage in this animal model.

PMID- 15567334
TI  - Expression of insulin-like growth factor 1 and receptor in ischemic rats treated
      with human marrow stromal cells.
AB  - Human bone marrow stromal cells (hMSCs) enhance neurological recovery after
      stroke in rodents, possibly via induction of growth factors. We therefore elected
      to test the effects of hMSC treatment on insulin-like growth factor 1 (IGF-1),
      which plays an important role in growth, development, neuroprotection and repair
      in the adult. Rats (n=57) were subjected to permanent middle cerebral artery
      occlusion (MCAo) and injected intravenously with 3 x 10(6) hMSCs or phosphate
      buffered saline (PBS) at 1 day after MCAo. Functional outcome was measured after
      MCAo using a modified Neurological Severity Score (mNSS). Gene expression of IGF
      1 and IGF-1 receptor (IGF-1R) in the ischemic brain tissue were measured at 2 and
      7 days after MCAo using reverse transcription-polymerase chain reaction (RT-PCR).
      Immunohistochemistry was performed to measure the expression of bromodeoxyuridine
      (BrdU), doublecortin (DCX), IGF-1 and IGF-1R at 7, 14 and 30 days after MCAo.
      Treatment of MCAo with hMSCs significantly improved functional recovery from 14
      to 30 days. MAB1281-labeled hMSCs entered the ischemic brain and increased time
      dependently. hMSC treatment significantly increased IGF-1 mRNA and BrdU(+),
      DCX(+), IGF-1(+) and IGF-1R(+) cells compared to PBS-treated rats (p<0.05). The
      percentage of BrdU(+) or DCX(+) cells colocalized with IGF-1 increased in the
      hMSC-treated rats compared to the PBS-treated rats (p<0.05). IGF-1 and IGF-1R may
      contribute to improved functional recovery and increased neurogenesis after
      treatment of stroke with hMSCs.

PMID- 15567336
TI  - Comparative hydrolysis of extracellular adenine nucleotides and adenosine in
      synaptic membranes from porcine brain cortex, hippocampus, cerebellum and medulla
      oblongata.
AB  - We have investigated the metabolism of extracellular adenine nucleotides and
      adenosine in porcine brain. The cortex synaptic plasma membranes hydrolyzed ATP
      to ADP, AMP and adenosine. We also observed a slow hydrolysis of adenosine with
      the concomitant accumulation of inosine. These results indicate that NTPDase1,
      NTPDase2, ecto-5'-nucleotidase, and adenosine deaminase are present in cortex
      synaptic membranes from porcine brain. We further showed that all these enzymes
      are also abundant in synaptic membranes from hippocampus, cerebellum, and medulla
      oblongata and compared their specific activities. Brain cortex and hippocampus
      exhibited higher activities of NTPDase1 and NTPDase2 than cerebellum and medulla
      oblongata. It was consistent with the high level of the expression of NTPDases in
      the two first structures. Adenosine deaminase activity was found in all brain
      structures analyzed; however, it was lower than the activity of ecto
      nucleotidases. Taken together, our data suggest that investigated enzymes have a
      ubiquitous abundance in porcine brain, and observed differences in their
      activities in cortex, hippocampus, cerebellum, and medulla oblongata may
      correlate with the pattern of P2 receptor expression in these brain areas. In
      addition, low activity of adenosine deaminase may indicate that nonenzymatic
      mechanism(s) are responsible for the termination of P1 receptor signaling in
      porcine brain.

PMID- 15567335
TI  - Distribution of methionine and leucine enkephalin neurons within the social
      behavior circuitry of the male Syrian hamster brain.
AB  - Enkephalin plays a role in the social behaviors of many species, but no
      corresponding role for this peptide has been investigated in the male Syrian
      hamster, a species in which brain nuclei controlling social behaviors have been
      identified. Previous studies have shown the distribution of dynorphin and beta
      endorphin throughout social behavior circuits within the male hamster brain. To
      date, the only studies of enkephalin in the hamster brain address the
      distribution of this peptide in the olfactory bulb and hippocampus. The present
      study provides a complete map of enkephalinergic neurons within the forebrain and
      midbrain of the male Syrian hamster and addresses the question of whether
      enkephalin immunoreactive (Enk-ir) cells are found within brain regions relevant
      to male hamster social behaviors. Following immunocytochemistry for either
      methionine enkephalin (met-enkephalin) or leucine enkephalin (leu-enkephalin), we
      observed enkephalin localization consistent with data that have previously been
      reported in the rat, with notable exceptions including lateral septum,
      ventromedial nucleus of the hypothalamus and cingulate gyrus. Additionally, met-
      and leu-enkephalin localization patterns largely overlap. Consistent with the
      post-translational processing of preproenkephalin, met-enkephalin was more
      abundant than leu-enkephalin both within individual cells (darker staining), and
      within given brain nuclei (more met-enkephalin immunoreactive cells). Two
      exceptions were the posterointermediate bed nucleus of the stria terminalis,
      containing more neurons heavily labeled for leu-enkephalin, and the main
      olfactory bulb, where only met-enkephalin was observed. Of most interest for this
      study was the observation of Enk-ir cells and terminals in areas implicated in
      both sexual and agonistic behaviors in this species.

PMID- 15567337
TI  - Suppression of excitatory synaptic transmission can facilitate low-calcium
      epileptiform activity in the hippocampus in vivo.
AB  - It has been reported that the inhibitory postsynaptic potential (IPSP) is
      abolished before the excitatory postsynaptic potential (EPSP) when the
      extracellular concentration of Ca(2+) ([Ca(2+)](o)) is removed gradually in
      hippocampal slices. However, the low-Ca(2+) nonsynaptic epileptiform activity
      does not appear until the [Ca(2+)](o) is decreased to a level sufficient to
      depress the excitatory synaptic transmission. This suggests the hypothesis that
      the suppression of excitatory synaptic transmission itself could facilitate the
      generation of epileptiform activity. In the present study, we tested this
      hypothesis and developed a new model of nonsynaptic epileptiform activity by
      gradually raising the neuronal excitability and blocking the synaptic
      transmission with high K(+), zero Ca(2+) and calcium chelator ethylene glycol-bis
      (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the CA1 region of
      hippocampus in vivo. The changes of synaptic transmission and recurrent
      inhibitory activity during this process were evaluated by measuring the amplitude
      of the population spikes (PS) in response to paired-pulse orthodromic
      stimulation. The results show that the epileptiform activity appeared only when
      the excitatory synaptic transmission was depressed by further lowering
      [Ca(2+)](o) with EGTA. Similar epileptiform activity could be induced when EGTA
      was replaced by the excitatory postsynaptic amino acid antagonists D-(-)-2-amino
      5-phosphonopentanoic acid (APV) plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) or
      APV alone but not DNQX alone. The combination application of APV and cadmium
      enhanced the epileptiform activity. These results suggest that the suppression of
      excitatory synaptic transmission can facilitate the appearance of epileptiform
      activity in solution with high K(+) and low Ca(2+) in vivo. These data provide
      new information to be considered in the development of antiepileptic drugs. They
      also suggest a possible mechanism to explain the fact that low-frequency
      electrical stimulation can suppress epileptiform activity.

PMID- 15567338
TI  - Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons
      against MPTP neurotoxicity in mice.
AB  - We examined the neuroprotective effects of a novel astrocyte-modulating agent,
      arundic acid (ONO-2506), in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      mouse model of Parkinson's disease. Male C57BL/6 mice received four
      intraperitoneal injections of MPTP (20 mg/kg) at 2 h intervals. Dopamine content
      in the striatum was reduced to 21% of the normal control after 7 days. Treatment
      with arundic acid (30 mg/kg, i.p.) administered 1 min, 6 h, 24 h, 48 h, and 72 h
      after the last MPTP injection prevented the dopamine depletion (52% of the
      control, p<0.01). In addition, this treatment resulted in behavioral benefits.
      Behavioral testing showed that MPTP-injected mice exhibited motor deficits in the
      pole test and catalepsy test after 7 days, but arundic acid prevented the
      appearance of motor abnormalities in these tests. The MPTP-injected animals
      exhibited an 87% loss of tyrosine hydroxylase-containing dopaminergic neurons in
      the substantia nigra after 7 days, but the arundic acid-treated mice showed only
      a 56% reduction (p<0.01). GFAP-positive reactive astrocytes were accumulated in
      the striatum and substantia nigra 7 days after the MPTP injection, whereas
      arundic acid treatment induced an earlier appearance of reactive astrocytes by 3
      days. The reactive astrocytes increased the production of S-100 protein, which is
      thought to promote neuronal damage, but arundic acid suppressed the expression of
      S-100. Thus, arundic acid protected dopaminergic neurons against MPTP
      neurotoxicity in mice and ameliorated neurological deficits. The results suggest
      that the neuroprotection is mediated through the modulation of astrocytic
      activation, including the inhibition of S-100 protein synthesis.

PMID- 15567339
TI  - Serotonergic mechanism of the lateral parabrachial nucleus and relaxin-induced
      sodium intake.
AB  - It has been shown that central or peripheral injections of the peptide relaxin
      induces water intake, not sodium intake in rats. Important inhibitory mechanisms
      involving serotonin and other neurotransmitters in the control of water and NaCl
      intake have been demonstrated in the lateral parabrachial nucleus (LPBN). In the
      present study, we investigated the effects of bilateral injections of
      methysergide (serotonergic receptor antagonist) into the LPBN on
      intracerebroventricular (i.c.v.) relaxin-induced water and NaCl intake in rats.
      Additionally, the effect of the blockade of central angiotensin AT(1) receptors
      with i.c.v. losartan on relaxin-induced water and NaCl intake in rats treated
      with methysergide into the LPBN was also investigated. Male Holtzman rats with
      cannulas implanted into the lateral ventricle (LV) and bilaterally in the LPBN
      were used. Intracerebroventricular injections of relaxin (500 ng/1 microl)
      induced water intake (5.1+/-0.7 ml/120 min), but not significant 1.8% NaCl intake
      (0.5+/-0.4 ml/120 min). Bilateral injections of methysergide (4 microg/0.2
      microl) into the LPBN strongly stimulated relaxin-induced 1.8% NaCl intake
      (34.5+/-10.9 ml/120 min) and slightly increased water intake (10.5+/-4.9 ml/120
      min). The pretreatment with i.c.v. losartan (100 microg/1 microl) abolished the
      effects of i.c.v. relaxin combined with LPBN methysergide on 1.8% NaCl intake
      (0.5+/-0.4 ml/120 min). Losartan (100 microg/1 microl) also abolished relaxin
      induced water intake in rats injected with methysergide into the LPBN (1.6+/-0.8
      ml/120 min) or not (0.5+/-0.3 ml/120 min). Losartan (50 microg/1 microl)
      partially reduced the effects of relaxin. The results show that central relaxin
      interacting with central angiotensinergic mechanisms induces NaCl intake after
      the blockade of LPBN serotonergic mechanisms.

PMID- 15567340
TI  - N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) suppresses neuritic
      degeneration caused by different experimental paradigms including in vitro
      Wallerian degeneration.
AB  - Accumulating evidence indicates that neurite degeneration occurs via a distinct
      mechanism from somal death programs. We have previously shown that neuritic ATP
      level in sympathetic neurons decreases, whereas somal ATP level remains unaltered
      during degeneration caused by the microtubule-disrupting agent, vinblastine.
      Moreover, caspase activation occurs only in cell soma, supporting the view of
      somal apoptosis and neuritic necrosis. Therefore, the ATP level of neurites is
      crucial for their degeneration; it appears to correlate with membrane blebbing or
      beading which precedes late whole fragmentation of neurites under these
      conditions. Based on these metabolic and morphological criteria, we have tested
      the effects of various protease inhibitors on vinblastine-induced neurite
      degeneration in superior cervical ganglia from neonatal mice. Among agents
      tested, N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), the trypsin-like
      serine protease inhibitor, but not N-p-tosyl-L-phenylalanine chloromethyl ketone
      (TPCK), the chymotrypsin-like serine protease inhibitor, protected sympathetic
      neurites from beading formation, neuritic fragmentation and a decrease in their
      ATP level. The commitment time for the saving effect of TLCK occurred around 7 h
      following treatment with vinblastine, at a time point after microtubule
      degradation (2 h) and before massive beading formation (later than 12 h).
      Moreover, TLCK was also capable of suppressing Wallerian degeneration in culture
      and neuritic degeneration following withdrawal of NGF in a dose-dependent manner.
      These results strongly suggest that TLCK intervenes in a common step in the
      cascade of neuritic degeneration caused by these different experimental paradigms
      and provides a helpful clue for identifying such a molecular step.

PMID- 15567341
TI  - Autologous transplantation of expanded neural precursor cells into the
      demyelinated monkey spinal cord.
AB  - The objective of this study was to establish if neural precursor cells could
      safely be developed from biopsy of the subventricular zone (SVZ) in the non-human
      primate (marmoset), and to determine their myelinating potential after autologous
      transplantation into a demyelinated lesion. Small amounts of tissue were safely
      collected from the subventricular-subependymal zone of the adult primate brain
      under ultrasonography without any neurological deficit. Neural precursor cells
      were isolated and expanded in the presence of mitogen in vitro. The dorsal
      columns of the adult marmoset spinal cord were demyelinated by X-irradiation and
      intraspinal injections of ethidium bromide in the center of the radiation field.
      Cell suspensions of the neural precursors were microinjected through a
      micropipette into the demyelinated lesion site in the spinal cord. Lesions were
      histologically examined 3 weeks after transplantation. Light and electron
      microscopic examination of plastic embedded sections revealed a significant
      number of myelinating profiles in the transplantation zone; no myelination was
      observed in control lesions. The myelinated axons had predominantly peripheral
      patterns of myelination. These results demonstrate that autologous
      transplantation of neural precursor cells in the adult nonhuman primate can
      remyelinate demyelinated central nervous system (CNS) axons, thus suggesting the
      potential utility of such an approach in demyelinating lesions in humans.

PMID- 15567342
TI  - Electroacupuncture induces c-Fos expression in the rostral ventrolateral medulla
      and periaqueductal gray in cats: relation to opioid containing neurons.
AB  - Our previous studies have shown that electroacupuncture (EA) at the Neiguan
      Jianshi (P5-P6) acupoints inhibits sympathetic outflow and attenuates excitatory
      visceral cardiovascular reflexes through enkephalin- or beta-endorphin-related
      opioid receptors in the rostral ventrolateral medulla (rVLM). It is not known
      whether EA at these acupoints activates neurons containing enkephalin or beta
      endorphin in the rVLM as well as in the periaqueductal gray (PAG) that are
      involved in EA-mediated central neural regulation of sympathetic activity. The
      present study evaluated activated neurons in the rVLM and PAG by detecting c-Fos
      immunoreactivity, and identified the relationship between c-Fos nuclei and
      neuronal structures containing enkephalin or beta-endorphin in these regions. To
      enhance the detection of cell bodies containing enkephalin or beta-endorphin,
      colchicine (90-100 microg/kg) was injected into the subarachnoid space in
      anesthetized cats 28-30 h prior to EA or the sham-operated control for EA.
      Following bilateral barodenervation and cervical vagotomy, EA (1-4 mA, 2 Hz, 0.5
      ms) was performed at the P5-P6 acupoints (overlying median nerve; n=7) for 30
      min. Identical procedures, with the exception of electrical stimulation, were
      carried out in five control animals. EA decreased blood pressure (BP) in four of
      seven cats (5-15 mm Hg) while the sham procedure for EA produced no responses.
      Perikarya containing enkephalin were found in the rVLM and rarely in the PAG,
      while no cell bodies labeled with beta-endorphin were identified in either
      region. Compared to animals in the control group, more c-Fos immunoreactivity,
      located principally in close proximity to fibers containing enkephalin or beta
      endorphin, was observed in the rVLM and ventrolateral PAG (vlPAG) in EA-treated
      cats. Moreover, neurons double-labeled with c-Fos and enkephalin in the rVLM were
      significantly increased in cats following EA stimulation (P<0.05). These data
      indicate that EA at the P5-P6 acupoints activates neurons in the rVLM and vlPAG.
      These activated neurons contain enkephalin in the rVLM, and most likely interact
      with nerve fibers containing enkephalin or beta-endorphin in both the rVLM and
      vlPAG. The results from this study provide the first anatomical evidence showing
      that EA at the P5-P6 acupoints has the potential to influence neuronal structures
      (perikarya, axons and/or dendrites) containing enkephalin or beta-endorphin in
      specific regions of the brain stem. These neurons likely form the substrate for
      EA's influence on sympathoexcitatory cardiovascular reflexes.

PMID- 15567343
TI  - Insulin-like growth factor-I receptor and estrogen receptor crosstalk mediates
      hormone-induced neurite outgrowth in PC12 cells.
AB  - Estradiol (E(2)) and insulin-like growth factor-I (IGF-I) can act independently
      or in concert to promote neurite outgrowth in vivo and in cultured neurons. This
      study examined the role of crosstalk between estrogen receptor (ER)alpha and the
      IGF-I receptor as a critical mediator of hormone- and growth factor-dependent
      neurite outgrowth in a homogenous cell system. We used control PC12 cells and
      PC12 cells stably transfected with ER alpha, both of which express IGF-I
      receptor. Cells were treated for 1 week with vehicle, 1 nM E(2) or 100 ng/ml IGF
      I alone or with E(2) or IGF-I in the presence of either the IGF-I receptor
      antagonist JB1 or the ER antagonist ICI 182,780. IGF-I significantly increased
      neurite outgrowth, as measured by the percentage of process-bearing cells, and
      absolute neurite length per cell in both control and ER alpha-transfected PC12
      cells. In contrast, E(2) increased process formation and extension only in PC12
      cells that were stably transfected with ER alpha. ICI 182,780 and JB1 blocked the
      IGF-I-induced increases in neurite length in both cell types. The efficacy of ICI
      182,780 in control PC12 cells may have been due to the upregulation of ER alpha
      in these cells by the 7-day treatment with IGF-I. The ER and IGF-I receptor
      antagonists similarly blocked the E(2)-induced increase in neurite lengths in ER
      alpha-transfected cells. Immunofluorescent analysis of the cellular distribution
      of an axonal marker, phospho-neurofilament, verified that the processes extended
      by PC12 cells were neurites. These data suggest that receptor crosstalk between
      IGF-I receptors and ER alpha has an important role in neurite formation and
      extension even in a single-cell system.

PMID- 15567344
TI  - Endothelin-mediated induction of heme oxygenase-1 in the spinal cord is
      attenuated in transgenic mice overexpressing superoxide dismutase.
AB  - Spinal cord blood flow and the induction of heme oxygenase-1 (HO-1), an indicator
      of oxidative stress, were studied in the spinal cords of adult wild-type and
      transgenic mice overexpressing the antioxidant copper, zinc superoxide dismutase
      (CuZn SOD) after intrathecal administration of the potent vasoactive peptide
      endothelin-1 (ET-1). Gelfoam, saturated with ET-1 (40, 80, or 400 micromol/L),
      was positioned in the intrathecal space at the midthoracic level in anesthetized
      animals. Blood flow was continuously monitored by laser Doppler for 10 min after
      the intrathecal application of ET-1. There was a significant reduction in spinal
      cord blood flow to approximately 40% of control values by 10 min after the
      intrathecal application of the peptide in both wild-type and transgenic mice.
      Moreover, SB209670, a nonselective endothelin receptor antagonist, blocked this
      reduction in flow. Each animal was euthanized 24 h after the intrathecal
      administration of ET-1, and the spinal cord was prepared for quantitative
      immunocytochemistry. HO-1 was primarily induced in astrocytes near the dorsal
      surface of the spinal cord in wild-type mice. This induction was attenuated in
      both wild-type, treated with SB209670, and untreated transgenic mice. Together,
      these findings suggest that ET-1 mediates oxidative stress in the spinal cord
      through the modulation of spinal cord blood flow.

PMID- 15567345
TI  - Effects of hyperglycemia and hypercapnia on lipid metabolism during complete
      brain ischemia.
AB  - Ischemic damage is greatly enhanced by preischemic hyperglycemia or hypercapnia,
      which affects many intracellular responses including protein kinase C (PKC)
      translocation. We explored whether hyperglycemic or hypercapnic ischemia affects
      lipid metabolism, especially ischemia-induced release of free fatty acids (FFAs)
      and diacylglycerols (DAGs). A change in intraischemic level of acidosis was
      induced either by injecting glucose (hyperglycemic, HG) or by adding CO(2)
      (hypercapnic, HC). Complete cerebral ischemia was induced, and the brain was
      frozen in situ after 3, 5, and 10 min at 37 degrees C. Frontoparietal neocortex
      was dissected for FFA and DAG lipid analysis by thin-layer chromatography and gas
      liquid chromatography. Significant differences were shown between normoglycemic
      and either hypercapnic or hyperglycemic values for individual and total FFAs. A
      significant delay in the release of FFA in ischemia with hyperglycemia or
      hypercapnia was observed. Significant differences were also shown in individual
      DAG-acyl groups and total DAGs. Hyperglycemic or hypercapnic ischemia resulted in
      a significant decrease of DAG at 10 min of ischemia. This was unexpected because
      a previous study showed that PKC translocation was significantly enhanced under
      similar condition at this time point. Upon cellular depolarization, massive
      influx of calcium and FFA accumulation may decrease the PKC dependence of DAG for
      translocation. In addition, PKC activation may lead to a negative feedback
      inhibition of phospholipase C.

PMID- 15567346
TI  - Inhibition of energy metabolism in cerebral cortex of young rats by the medium
      chain fatty acids accumulating in MCAD deficiency.
AB  - Patients affected by medium-chain acyl CoA dehydrogenase (MCAD) deficiency, a
      frequent inborn error of metabolism, suffer from acute episodes of
      encephalopathy. However, the mechanisms underlying the neuropathology of this
      disease are poorly known. In the present study, we investigated the in vitro
      effect of the medium-chain fatty acids (MCFA), at concentrations varying from
      0.01 to 3 mM, accumulating in MCAD deficiency on some parameters of energy
      metabolism in cerebral cortex of young rats. (14)CO(2) production from [U(14)]
      glucose, [1-(14)C] acetate and [1,5-(14)C] citrate was evaluated by incubating
      cerebral cortex homogenates from 30-day-old rats in the absence (controls) or
      presence of octanoic acid, decanoic acid or cis-4-decenoic acid. OA and DA
      significantly reduced (14)CO(2) production from acetate by around 30-40%, and
      from glucose by around 70%. DA significantly reduced (14)CO(2) production from
      citrate by around 40%, while OA did not affect this parameter. cDA inhibited
      (14)CO(2) production from all tested substrates by around 30-40%. The activities
      of the respiratory chain complexes and of creatine kinase were also tested in the
      presence of DA and cDA. Both metabolites significantly inhibited cytochrome c
      oxidase activity (by 30%) and complex II-III activity (DA, 25%; cDA, 80%).
      Furthermore, only cDA inhibited complex II activity (by 30%), while complex I-III
      and citrate synthase were not affected by these MCFA. On the other hand, only cDA
      reduced the activity of creatine kinase in total homogenates, as well as in
      mitochondrial and cytosolic fractions from cerebral cortex (by 50%). The data
      suggest that the major metabolites which accumulate in MCAD deficiency, with
      particular emphasis to cDA, compromise brain energy metabolism. We presume that
      these findings may contribute to the understanding of the pathophysiology of the
      neurological dysfunction of MCAD deficient patients.

PMID- 15567347
TI  - Changes of melanin-concentrating hormone related to LHRH release in the median
      eminence of rats.
AB  - The present research was carried out to study the distribution of melanin
      concentrating hormone (MCH) fibers in the median eminence of rats and to evaluate
      if changes in the MCH content of the median eminence could be related to the
      release of LHRH. Immunocytochemical studies in the median eminence of males and
      estrous females showed the presence of MCH fibers, mainly in its internal layer.
      Diestrous and proestrous animals displayed MCH immunoreactivity in both the
      internal and external layers of the median eminence. Longitudinal sections of the
      median eminence in proestrous animals showed that MCH-immunoreactive (ir) density
      is higher at 12 than at 9 h in both layers of the median eminence. MCH was
      assayed by radioimmunoassay in median eminences of males and in females in all
      stages of the estrous cycle at 10 h. It was observed that the content of MCH at
      diestrus-1 and -2 was higher than in estrus and in male rats. In the day of
      proestrus, MCH and LHRH were assayed at 10, 12, 13, 14, 15 and 17 h. At 12 h, the
      content of MCH and LHRH showed the maximal values. At 13 h, MCH content showed a
      decline, while LHRH was still high. At 14 h, the LHRH content started to
      decrease. The present results suggest that MCH is involved in the regulation of
      LHRH release in the female rat.

PMID- 15567348
TI  - Administration of nicotine to adolescent rats evokes regionally selective
      upregulation of CNS alpha 7 nicotinic acetylcholine receptors.
AB  - Alpha 7 Nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis,
      synaptogenesis and synaptic plasticity, and are therefore targets for
      developmental neurotoxicants. We administered nicotine to adolescent rats and
      evaluated the effects on alpha 7 nAChRs in the striatum, brainstem and
      cerebellum. During the period of nicotine administration (30-47.5 days of age),
      nicotine elicited alpha 7 nAChR upregulation with a regional hierarchy of
      striatum>brainstem>cerebellum. Values returned to normal or became slightly
      subnormal almost immediately after the cessation of treatment (50 days of age)
      with no further changes through 75 days of age. The temporal and regional
      patterns of the effects on alpha 7 nAChRs were distinct from those reported
      earlier for the alpha 4 beta 2 subtype, and neither adult nor fetal/neonatal
      administration upregulates the alpha 7 subtype in the striatum. Targeting of the
      striatum is thus unique to nicotine exposure during adolescence and parallels
      earlier work showing regionally selective effects of this treatment on synaptic
      signaling. We obtained preliminary evidence for nicotine-induced oxidative stress
      as a potential contributory mechanism. The present findings reinforce the concept
      of biologically distinct effects of nicotine in the adolescent brain and provide
      evidence for a mechanistic involvement of alpha 7 nAChRs in its unique effects
      during this developmental period.

PMID- 15567349
TI  - A modeling approach to the impact of HIV mutations on the immune system.
AB  - A dynamical system modeling the HIV infection, including a mutation occurrence
      process, is used, after simplifications, to show the impact of the viral
      diversity on the immune response and disease dynamics, by introducing an
      indicator of the immune system behavior, the immunological recognition efficacy
      (IRE) index. The existence, the expression and the stability of the endemically
      infected steady state of the IRE index-based model, as function of this index,
      are mathematically analyzed. The monotony of the steady state with respect to the
      IRE index is studied and an asymptotic analysis of the dynamical system
      performed. It is shown that the IRE index-based model provides a bound to the
      responses of the initial complex dynamical system. The biological interpretation
      of these mathematical results is the exhaustion of the immune system as a
      consequence of the continuous generation of viral mutants.

PMID- 15567350
TI  - An EMG-driven model of the upper extremity and estimation of long head biceps
      force.
AB  - An electromyography (EMG) driven model of the upper extremity has been developed
      that incorporates musculoskeletal geometry of the glenohumeral and elbow joints,
      estimated relevant physiologic muscle parameters including optimal muscle
      lengths, and EMG activity. The model is designed to predict forces in muscles
      spanning the glenohumeral joint resulting from functionally relevant tasks. The
      model is composed of four sub-models that comprise a mathematical as well as
      graphical three-dimensional representation of the upper extremity: a
      musculoskeletal model for estimation of muscle-tendon lengths and moment arms, a
      Hill-based muscle force model, a model for estimating optimal muscle lengths, and
      a model for estimation of muscle activation from EMG signal of the biceps. The
      purpose of this paper is to describe the components of the model, as well as the
      data required to drive the model. Collection of data is described in the context
      of applying the model to determine biceps muscle forces for testing of functional
      tasks. Results obtained from applying the model to analyze the functional tasks
      are summarized, and model strengths and limitations are discussed.

PMID- 15567351
TI  - 3D-Visualization of particle deposition patterns in the human lung generated by
      Monte Carlo modeling: methodology and applications.
AB  - An advanced stochastic model is described which enables the generation of three
      dimensional particle deposition patterns in the human lung. While particle
      trajectories are represented as a combination of randomly oriented vectors in a
      coordinate system with the trachea defining the z direction, deposition sites of
      single particles are determined by using a grid of specific volume elements
      (voxels). After storage in an array, the spatial coordinates are visualized with
      an appropriate graphic editor, enabling the combination of respective deposition
      images with lung outlines and the creation of two-dimensional distributions by
      sectioning the three-dimensional structures at pre-defined positions.

PMID- 15567352
TI  - Comparison of the autoregressive modeling and fast Fourier transformation in
      demonstrating Doppler spectral waveform changes in the early phase of
      atherosclerosis.
AB  - In this study, we have performed fast Fourier transformation (FFT) and
      autoregressive (AR) signal processing of the Doppler signals at a nonstenotic
      arterial site in patients with atherosclerosis and healthy volunteers. We have
      not only utilized Doppler sonograms, but also facilitated the power spectral
      density distribution graphs using AR modeling and FFT. Our preliminary analysis
      show that AR modeling has a higher efficacy in demonstrating Doppler spectral
      waveform changes in the preclinic or silent phase of atherosclerosis. AR has
      especially revealed an outstanding difference in the calculation for frequency
      level of maximum power spectral density.

PMID- 15567353
TI  - Two-stage classification of respiratory sound patterns.
AB  - The classification problem of respiratory sound signals has been addressed by
      taking into account their cyclic nature, and a novel hierarchical decision fusion
      scheme based on the cooperation of classifiers has been developed. Respiratory
      signals from three different classes are partitioned into segments, which are
      later joined to form six different phases of the respiration cycle. Multilayer
      perceptron classifiers classify the parameterized segments from each phase and
      decision vectors obtained from different phases are combined using a nonlinear
      decision combination function to form a final decision on each subject.
      Furthermore a new regularization scheme is applied to the data to stabilize
      training and consultation.

PMID- 15567354
TI  - Neurons with radial basis like rate functions.
AB  - Artificial neural networks constructed with "locally tuned processing units" and
      more generally referred to as "radial basis function networks" have been proposed
      by a number of workers. In this communication, I submit a conjecture, based on
      indirect experimental and direct computational evidence of the Hodgkin-Huxley
      model, that there may be biological neurons in nervous systems for which the rate
      function is locally tuned. If proved to be valid, this conjecture may simplify
      neurodynamic models of some functions of nervous systems.

PMID- 15567357
TI  - Variations of structure and appearance of the oral mucosa.
AB  - Among the most important factors in a thorough clinical examination is the
      dentist's ability to recognize and make distinctions among normal oral
      structures, variations of normal structures, and pathologic entities. The
      practitioner's diagnostic acumen is essential to this process and is a skill
      gained and refined by clinical experience and continuing education. In this
      introductory article, the authors describe normal entities, anomalies, and benign
      soft tissue lesions of interest to the clinician. For presentation, these
      structures are organized according to their location within the oral cavity.

PMID- 15567358
TI  - Oral herpetic infections (HSV 1-8).
AB  - Oral herpes virus infections are commonly seen by the dental practitioner. Saliva
      is a reservoir for the herpes virus, and a variety of infections, both localized
      and systemic, may be induced by the virus. Patients who are immunocompromised may
      be at risk for serious and potentially life-threatening complications of herpes
      virus infections. This article highlights the basic virology and clinical
      manifestations of herpetic infections and the differential diagnosis and
      management of oral herpes virus infections.

PMID- 15567359
TI  - Recurrent aphthous stomatitis.
AB  - The cause of recurrent aphthous stomatitis (RAS) remains unknown despite
      considerable research. This article reviews the evidence for current theories
      regarding this disorder, including possible suspected relationships with
      microbial and immunologic factors, and presents medical diseases that mimic RAS
      lesions in certain patients. Topical management of the common form of minor RAS
      is described along with systemic therapy currently available to patients with
      severe forms of this disease.

PMID- 15567360
TI  - Oral fungal infections.
AB  - Candidiasis is the most common oral fungal infection diagnosed in humans.
      Candidiasis may result from immune system dysfunction or as a result of local or
      systemic medical treatment. Because oral candidiasis is generally a localized
      infection, topical treatment methods are the first line of therapy, especially
      for the pseudomembranous and erythematous variants. Patients with dental
      prostheses should also be advised to disinfect the prosthesis routinely during
      the candidal treatment period, because the prosthesis may serve as a source of
      reinfection. Additionally, patients should be advised that oral hygiene aids,
      such as toothbrushes and denture brushes, may also be contaminated and should be
      discarded or disinfected. A disinfecting solution of equal parts of hydrogen
      peroxide and water may be used. Likewise, 2% chlorhexidine gluconate solution may
      be used asa disinfecting solution for dental prostheses and oral hygiene aids.
      Occasionally the clinician encounters a more resistant form of oral candidiasis
      such as the hyperplastic variant or a variant that does not respond to topical
      therapy. Appropriate systemic therapy should be employed for the treatment of
      these infections. Additionally, a biopsy should be undertaken in individuals with
      the hyperplastic variant of Candida because there is some degree of risk for
      malignant transformation. Deep fungal infections should be managed in association
      with appropriate medical specialists to rule out other systemic involvement. The
      dental health care provider plays an important part in the diagnosis and
      management of fungal disease, and therefore clinicians should be aware of the
      presenting signs and symptoms or oral fungal disease.

PMID- 15567361
TI  - Erythema multiforme: a review and contrast from Stevens-Johnson syndrome/toxic
      epidermal necrolysis.
AB  - Erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis are
      separate diseases. Recent evidence suggests that they have different etiologies
      and require different treatments. This article provides an overview of the two
      conditions with emphasis on the differences between them. An outline of the
      diagnosis and management of the diseases is included.

PMID- 15567362
TI  - Lichen planus, lichenoid drug reactions, and lichenoid mucositis.
AB  - Lichen planus is a common mucocutaneous disease affecting a significant portion
      of the general population. This article reviews the most current concepts on the
      epidemiology, etiology, pathogenesis, clinical presentations, and treatment of
      oral lichen planus, lichenoid drug reactions, and lichenoid mucositis.

PMID- 15567363
TI  - Mucous membrane pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) is a chronic, subepithelial autoimmune disease,
      which predominantly involves mucosal surfaces and results in mucosal blistering,
      ulceration, and subsequent scarring. This article discusses the epidemiology,
      clinical presentation, pathophysiology, diagnosis, and management of MMP, with
      mention of related subepithelial bullous dermatoses.

PMID- 15567364
TI  - Pemphigus.
AB  - Pemphigus is an umbrella term for more than 10 different epidermal disease types
      and subtypes currently classified under this name. Characteristic for pemphigus
      are the presence of autoantibodies against epidermal cell adhesion structures
      (desmosomes), leading to a breakdown of cutaneous and mucosal barriers. The two
      most important disease types for dentists are pemphigus vulgaris and
      paraneoplastic pemphigus because they almost invariably present with oral
      manifestations. This article highlights current knowledge on the pathophysiology,
      the clinical signs, and the practical clinical diagnostic approach to these two
      serious disorders and treatment.

PMID- 15567365
TI  - Oral manifestations of patients with lupus erythematosus.
AB  - Lupus erythematosus manifests as cutaneous variants, such as discoid lupus
      erythematosus or systemic lupus erythematosus. Systemic lupus erythematosus is a
      multisystem autoimmune disease characterized by general autoantibody production
      and a wide range of mucocutaneous, renal, neuropsychiatric, cardiovascular,
      infectious, and hematologic manifestations. This article discusses the prevalence
      of and considerations for oral mucosal lesions in lupus erythematosus and the
      impact of the various disease manifestations of systemic lupus erythematosus on
      dental management.

PMID- 15567366
TI  - Oral cancer: leukoplakia and squamous cell carcinoma.
AB  - This article reviews the epidemiology, etiologic risk factors, clinical
      presentation, recognition, and diagnosis of oral precancer and cancer. The actual
      treatment and complications from treatment of oral cancer are discussed only
      briefly.

PMID- 15567367
TI  - Oral mucositis.
AB  - Oral mucositis refers to erythematous, erosive, and ulcerative lesions of the
      oral mucosa seen in two patient populations: (1) head and neck cancer patients
      undergoing radiation therapy to fields involving the oral cavity, and (2)
      patients receiving high-dose chemotherapy for cancer. Oral mucositis is a
      significant and dose-limiting toxicity of cancer therapy, with important clinical
      and economic implications. This article reviews the current knowledge on the
      pathogenesis, clinical presentation, diagnosis, and management of oral mucositis.

PMID- 15567368
TI  - Pigmented lesions of the oral cavity.
AB  - The management of pigmented oral lesions varies based on the diagnosis, ranging
      from the extremes of patient reassurance to radical surgical excision. This
      article delineates the factors that will help the clinician differentially
      diagnose pigmented lesions of the oral cavity. The parameters of care regarding
      the spectrum of pigmentations are also reviewed.

PMID- 15567369
TI  - Granulomatous diseases of the oral tissues: differential diagnosis and update.
AB  - Because of the relatively nonspecific clinical findings associated with a variety
      of granulomatous diseases, a microscopic diagnosis of granulomatous inflammation
      often presents a diagnostic dilemma for the clinician. The most common
      differential diagnosis includes foreign body reactions, infection, Crohn's
      disease, sarcoidosis, and orofacial granulomatosis. However, a variety of other
      conditions may be associated with granuloma formation. Often an extensive
      clinical, microscopic, and laboratory evaluation may be required to identify the
      source of the granulomatous inflammation. This article highlights the origin,
      clinical manifestations, current diagnostic modalities, and treatment of specific
      granulomatous diseases that may be encountered in clinical practice.

PMID- 15567370
TI  - Common benign oral soft tissue masses.
AB  - This article reviews some of the more common benign oral soft tissue masses with
      emphasis on their etiology, epidemiology, clinical presentation, histopathology,
      and treatment. These lesions include traumatic fibroma, mucocele,
      warts/papilloma, pyogenic granuloma, peripheral giant cell granuloma, generalized
      gingival hyperplasia, gingival fibromatosis, lateral periodontal cyst, lipoma,
      and denture-induced hyperplasia.

PMID- 15567371
TI  - Pediatric soft tissue lesions.
AB  - Soft tissue oral and perioral lesions in the pediatric population are numerous
      and occur in various clinical presentations. Some conditions observed in children
      share characteristics with adult-onset disease. Other oral lesions are limited to
      the pediatric population. This article focuses on the more common soft tissue
      manifestations in children. Rather than a comprehensive review of pediatric oral
      pathology, the article offers an overview of selected clinical conditions often
      encountered in young patients.

PMID- 15567372
TI  - Orofacial disorders in children with HIV disease.
AB  - The most common orofacial disorders found among HIV-infected children are oral
      candidiasis, parotid gland enlargement, lymphadenopathy, and oral dryness. These
      changes are strongly related to immune suppression, immune deterioration, and HIV
      disease progression. The classification of oral lesions in pediatric patients
      needs to be updated to reflect the relationship between immunologic and virologic
      markers.

PMID- 15567373
TI  - Adsorption and heterocoagulation of nonionic surfactants and latex particles on
      cement hydrates.
AB  - The adsorption of nonionic surfactants of the alkyl-phenol-poly(ethylene oxide)
      family and of acrylic latex particles on several anhydrous (but hydrating) or
      fully hydrated mineral phases of Portland cement was studied. No or negligible
      adsorption of the surfactant was observed. This was assigned to the ionized
      character of the surface silanol groups in calcium-silicate-hydrates and to the
      strongly ionic character of the OH groups in calcium hydroxide and in the calcium
      sulfoaluminate-hydrates, which prevents the formation of surface-ethoxy hydrogen
      bonds. In contrast, provided they are properly stabilized by the surfactant, the
      latex particles form a loose monolayer on the surface of hydrating tricalcium
      silicate particles. The attractive interaction between the positive mineral
      surface and the negative latex surface appears to be the driving force for
      adsorption. In line with this, adsorption is reduced by sulfate anions, which
      adsorb specifically onto the silicate surface. Compared to tricalcium silicate,
      portlandite and gypsum interact only marginally with the latex particles. Our
      results show that the stability of the nonionic surfactant/latex/cement systems
      is essentially controlled by the latex colloidal stability and the latex-cement
      interactions, the surfactant having little direct interaction, if any, with the
      mineral surfaces.

PMID- 15567374
TI  - Selective and sequential adsorption of bovine serum albumin and lysozyme from a
      binary mixture on nanosized magnetic particles.
AB  - Magnetic particles about 10 nm in size were prepared by chemical precipitation
      under nitrogen and used for the selective and sequential adsorption of bovine
      serum albumin (BSA) (pI = 4.7) and lysozyme (LSZ) (pI = 1.1) under different
      conditions, such as pH and initial protein concentration. The separation ratio of
      BSA over LSZ at pH 4.6 is about 5, which is about 1.5 times the separation ratio
      of LSZ over BSA at pH 11.0. Only 10% of the preadsorbed BSA could be displaced by
      the sequential adsorption of LSZ at pH 11.0. On the other hand, 60% of the
      preadsorbed LSZ was desorbed due to the sequential adsorption of BSA at pH 4.6.
      Over 50% desorption of BSA or LSZ could be achieved either by 0.5 M Na(2)HPO(4)
      or 0.5 M NaH(2)PO(4) after 2 h. Over 80% of the enzymatic activity of LSZ was
      preserved when it was desorbed from magnetic particles.

PMID- 15567375
TI  - The effects of acid and alkali modification on the adsorption performance of
      fuller's earth for basic dye.
AB  - The objective of this work was to prepare modified adsorbents from fuller's earth
      (FE) by acid and alkali treatment for enhancement cationic dye adsorption.
      Toluidine blue (TB) was selected as adsorbate for evaluating the adsorption
      performance of fuller's earth samples, which was affected significantly by acid
      and alkali modification. The adsorption of TB was studied by visible spectra. The
      absorption band of the monomer at low loading of TB in FE suspension with respect
      to its maximum in aqueous solution is red-shifted, which is related to
      accessibility of dye interlamellar space in the presence of positively charged
      surface sites. Since all surfaces are negatively charged under experimental
      conditions, this effect has not been observed in acid- and alkali-treated FE
      suspensions. It was seen that the adsorption capacity of alkali-treated surface
      (FEAl) for TB was higher than these of acid-treated adsorbent (FEAc) and FE.
      Scanning electron micrographs (SEM) and X-ray diffraction (XRD) and fluorescence
      (XRF) spectra were applied to analyze the structure of the raw and modified FE
      samples. Absence of any identifiable amount of a crystalline compound in the
      solid reaction products after acid treatment was confirmed by XRD and SEM,
      whereas the crystalline form of FEAl was preserved. Experimental data for high
      concentration regions were well described by Freundlich and Langmuir adsorption
      equations. The thermodynamic parameters were estimated for FE, FEAc, and FEAl by
      using temperature dependence of adsorption equilibrium constants.

PMID- 15567376
TI  - Removal of 2,4-dichlorophenoxyacetic acid from aqueous solutions by partially
      characterized organophilic sepiolite: thermodynamic and kinetic calculations.
AB  - The adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) on organophilic
      sepiolite (dodecylammonium sepiolite, DAS) was studied as a function of solution
      concentration and temperature. The observed adsorption rates were found to be
      equal to the first-order kinetics. The rate constants were calculated for
      temperatures ranging between 25 and 40 degrees C at constant concentration. The
      adsorption energies, E, and adsorption capacity, q(m), for 2,4-D adsorption on
      organophilic sepiolite was estimated using the Dubinin-Radushkevic equation.
      Thermodynamic parameters (Deltag(a), Deltah(a), Deltas(a)) were determined by a
      new approximation from the isotherm of 2,4-D adsorption on DAS. Also, DeltaS(0)
      and DeltaH(0) values were calculated from the van't Hoff equation. These
      isotherms were modeled according to the Freundlich and Dubinin-Radushkevic
      adsorption equations. The amount of adsorption of this herbicide on organophilic
      sepiolite was found to be dependent on the relative energies of adsorbent
      adsorbate, adsorbate-solvent, and adsorbate-adsorbate interaction.

PMID- 15567377
TI  - Investigation of the factors affecting organic cation adsorption on some silicate
      minerals.
AB  - In this study, the effects of some factors on the adsorption of a basic dye
      (methylene blue) on bentonite and sepiolite samples were studied. These factors
      are cation (Na(+) and Ca(2+)) saturation of the samples and pH and ionic strength
      of the dye solution. The adsorption data were found to conform to the Langmuir
      equation within the concentration range studied and Langmuir constants were
      determined for each of the samples. The adsorption capacities of the samples were
      found to increase with cation saturation. Changes in the pH of the dye solution
      had no significant influence on the adsorption capacity and adsorption capacities
      were found to decrease with increasing ionic strength. The maximum sorption
      capacity of methylene blue exceeded the cation exchange capacity of bentonite and
      sepiolite.

PMID- 15567378
TI  - Modeling Pb sorption to microporous amorphous oxides as discrete particles and
      coatings.
AB  - Hydrous amorphous Al (HAO), Fe (HFO), and Mn (HMO) oxides are ubiquitous in the
      subsurface as both discrete particles and coatings and exhibit a high affinity
      for heavy metal contaminants. To assess risks associated with heavy metals, such
      as Pb, to the surrounding environment and manage remedial activities requires
      accurate mechanistic models with well-defined transport parameters that represent
      sorption processes. Experiments were conducted to evaluate Pb sorption to
      microporous Al, Fe, and Mn oxides, as well as to montmorillonite and HAO-coated
      montmorillonite. Intraparticle diffusion, a natural attenuating process, was
      observed to be the rate-limiting mechanism in the sorption process, where best
      fit surface diffusivities ranged from 10(-18) to 10(-15) cm(2) s(-1).
      Specifically, diffusivities of Pb sorption to discrete aluminum oxide, aluminum
      oxide-coated montmorillonite, and montmorillonite indicated substrate surface
      characteristics influence metal mobility where diffusivity increased as affinity
      decreased. Furthermore, the diffusivity for aluminum oxide-coated montmorillonite
      was consistent with the concentrations of the individual minerals present and
      their associated particle size distributions. These results suggest that
      diffusivities for other coated systems can be predicted, and that oxide coatings
      and montmorillonite are effective sinks for heavy metal ions.

PMID- 15567379
TI  - A comparative adsorption study with different industrial wastes as adsorbents for
      the removal of cationic dyes from water.
AB  - Four adsorbents have been prepared from industrial wastes obtained from the steel
      and fertilizer industries and investigated for their utility to remove cationic
      dyes. Studies have shown that the adsorbents prepared from blast furnace sludge,
      dust, and slag have poor porosity and low surface area, resulting in very low
      efficiency for the adsorption of dyes. On the other hand, carbonaceous adsorbent
      prepared from carbon slurry waste obtained from the fertilizer industry was found
      to show good porosity and appreciable surface area and consequently adsorbs dyes
      to an appreciable extent. The adsorption of two cationic dyes, viz., rhodamine B
      and Bismark Brown R on carbonaceous adsorbent conforms to Langmuir equation, is a
      first-order process and pore diffusion controlled. As the adsorption of dyes
      investigated was appreciable on carbonaceous adsorbent, its efficiency was
      evaluated by comparing the results with those obtained on a standard activated
      charcoal sample. It was found that prepared carbonaceous adsorbent exhibits dye
      removal efficiency that is about 80-90% of that observed with standard activated
      charcoal samples. Thus, it can be fruitfully used for the removal of dyes and is
      a suitable alternative to standard activated charcoal in view of its cheaper
      cost.

PMID- 15567380
TI  - Removal of lead ions in drinking water by coffee grounds as vegetable biomass.
AB  - In an attempt to reuse food waste for useful purposes, we investigated the
      possibility of using coffee grounds to remove lead ions from drinking water. We
      studied the lead ion adsorption characteristics of coffee beans and grounds by
      measuring their fat and protein content, adsorption isotherms for lead ions, and
      adsorption rates for lead ions. The number of lead ions adsorbed by coffee
      grounds did not depend on the kind of coffee beans or the temperature at which
      adsorption tests were performed. The rate of lead ion adsorption by coffee
      grounds was directly proportional to the amount of coffee grounds added to the
      solution. When coffee grounds were degreased or boiled, the number of lead ions
      decreased. When proteins contained in coffee grounds were denatured, the lead ion
      adsorption was considerably reduced. The lead ion adsorption capacity of coffee
      grounds decreased with increased concentration of perchloric acid used for
      treating them and disappeared with 10% perchloric acid. The experiments
      demonstrated that proteins contained in coffee beans depend upon the adsorption
      of lead ion. The present study gave an affirmative answer to the possibility of
      using coffee grounds, an abundant food waste, for removing lead ions from
      drinking water.

PMID- 15567381
TI  - Thermodynamic and kinetic investigations of PO3-4 adsorption on blast furnace
      slag.
AB  - The kinetics of adsorption of PO(3-)(4) by blast furnace slag were found to be
      fast, reaching equilibrium in 20 min and following a pseudo-second-order rate
      equation. The adsorption behavior of PO(3-)(4) on blast furnace slag has been
      studied as a function of the solution agitation speed, pH, and temperature.
      Results have been analyzed by Freundlich, Langmuir, BET, and Dubinin-Radushkevich
      (D-R) adsorption isotherms. The mean energy of adsorption, 10.31 kJ mol(-1), was
      calculated from the D-R adsorption isotherm. The rate constants were calculated
      for 293, 298, 303, and 308 K using a pseudo-second-order rate equation and the
      activation energy (E(a)) was derived using the Arrhenius equation. Thermodynamic
      parameters such as DeltaH(0), DeltaS(0), and DeltaG(0) were calculated from the
      slope and intercept of linear plot of lnK(D) against 1/T. The DeltaH(0) and
      DeltaG(0) values of PO(3-)(4) adsorption on the blast furnace slag show
      endothermic heat of adsorption. But there is a negative free energy value,
      indicating that the process of PO(3-)(4) adsorption is favored at high
      temperatures.

PMID- 15567382
TI  - The concept of "capacity" in zeolite ion-exchange systems.
AB  - In the present paper a study is conducted in order to distinguish the several
      types of capacity used in the literature on zeolite ion-exchange systems, to
      verify the use of each capacity type, and to analyze the several experimental
      methods used for capacity determination. Although the study is focused on zeolite
      clinoptilolite as a characteristic paradigm, its theoretical approaches and
      experimental findings and methods could also apply to other zeolites.

PMID- 15567383
TI  - Properties and structure of manganese oxide-coated clay.
AB  - In the environment, heavy metals are important contaminants that sorb to and
      accumulate in soils and sediments. Dominant minerals in the subsurface are oxides
      and clay, which occur as discrete particles and heterogeneous systems; these
      surfaces can significantly impact the mobility and bioavailability of metals
      through sorption. To better understand heterogeneous systems, amorphous (hydrous
      manganese oxide (HMO)) and crystalline manganese oxides (birnessite and
      pyrolusite) were coated on montmorillonite. However, the montmorillonite
      substrate potentially inhibited crystallization of the pyrolusite coating, and
      also resulted in a poorly crystalline birnessite. Mineralogy and morphology of
      the coated systems suggest an amorphous structure for HMO and uniform coverage
      for HMO and birnessite coatings; the presence of Si and Al indicates uncoated
      areas along intraplanar surfaces. The coating surface charge behaved similarly to
      that of discrete oxides and clay where the pH(znpc) of HMO- and birnessite-coated
      clay were 2.8 and 3.1, respectively. Surface area of the coated systems increased
      while the pore size distribution decreased as compared to the external surface
      area and pores of montmorillonite. X-ray absorption spectroscopy (XAS) revealed
      the local structural environment of Mn in the HMO- and birnessite-coated clay was
      consistent with the pure phase oxides: for HMO-coated clay 3.1 atoms of oxygen at
      1.89 +/- 0.02 A in the first shell and 2.7 atoms of manganese at 2.85 +/- 0.02 in
      the second shell; and, for birnessite-coated clay 6 atoms of oxygen at 1.91 +/-
      0.02 A in the first shell and 6 atoms of manganese at distance 2.99 +/- 0.02 A in
      the second shell. Overall, the surface properties suggest that the coating
      behaves like that of discrete oxides, an important sink for metal contaminants.

PMID- 15567384
TI  - Interfacial properties of poly(maleic acid-alt-1-alkene) disodium salts at
      water/hydrocarbon interfaces.
AB  - The interfacial properties of poly(maleic acid-alt-1-alkene) disodium salts at
      hydrocarbon/water interfaces are determined. In all the studied systems, the
      interfacial tension decreases markedly with the polyelectrolyte concentration as
      the side-chain length increases. The results of the standard free energy of
      adsorption, DeltaG(ads)(0), are a linear function of the number of carbon atoms
      in the polyelectrolyte side chain. The contribution to DeltaG(ads)(0) per mol of
      methylene group varies from -0.64 to -0.52 kJ/mol for the n-octane/water to n
      dodecane/water interfaces. DeltaG(ads)(0) data also reveal that the adsorption
      process is mainly determined by adsorption efficiency. Comparatively, the
      adsorption effectiveness seems to play a less important role. The theoretical
      interaction energies calculated for the insertion of one hydrocarbon molecule
      into the space formed by two neighboring polyelectrolyte side chains are in good
      agreement with the experimental results. The latter results are consistent with
      van der Waals-type interactions between the hydrocarbon molecules and the
      polyelectrolyte side chains.

PMID- 15567385
TI  - Interaction forces between cellulose microspheres and ultrathin cellulose films
      monitored by colloidal probe microscopy-effect of wet strength agents.
AB  - Colloidal probe microscopy was employed to study forces between cellulose
      surfaces upon addition of a series of cationic copolymers in aqueous solution, as
      model compounds for wet strength agents. The content of quaternary ammonium
      groups and primary amines was systematically varied in the cationic polymers, to
      distinguish between the importance of electrostatical and H-bonding effects.
      Cellulose microspheres were glued at the apex of tipless microfabricated
      cantilevers and used as colloidal probes. Ultra thin cellulose films and
      cellulose fibres were employed as model surfaces. The cellulose films of a
      thickness of about 5 nm were spin-coated from cellulose solution onto silicon
      substrates. The root-mean-square-roughness (RMS) was 0.3-0.8 nm. The cationic
      model polymers were compared to Servamine, a polymer employed as standard wet
      strength resin in papermaking industries. Force versus separation measurements
      showed a detailed picture of adhesion and contact breaking. Relatively strong
      adhesion of the order of 0.3 mJ/m(2) was observed with Servamine within a range
      of approximately 10 nm. At larger distances weak bond breaking and elastic chain
      pulling were identified. When approaching the surface one to two small jump-in's
      possibly related to strong binding of Servamine and subsequent attraction could
      be found in the case of Servamine. In contrast, all the model copolymers showed
      only a weak adhesion of 8-30 micro/m(2), i.e., an order of magnitude less than
      that of Servamine and subsequent elastic rupture domains. The contour length,
      persistence length and characteristic rupture distances were calculated by means
      of applying the WLC model. Measurements against cellulose fibres obtained from
      the production process proved the relevance of the model systems.

PMID- 15567386
TI  - Chemisorption of thiolated poly(ethylene oxide) to gold: surface chain densities
      measured by ellipsometry and neutron reflectometry.
AB  - Physical property studies of surfaces formed by chemisorption of polyethylene
      oxide (PEO) onto gold are reported. Such surfaces have potential as model
      materials for elucidation of the mechanism of resistance to protein adsorption by
      PEO surfaces. Thiolated monomethoxy poly(ethylene oxide) (PEO) was chemisorbed
      onto gold-coated silicon wafers under various conditions such that different
      surface chain densities were achieved. Chain density was varied by controlling
      PEO solubility (proximity to cloud-point conditions) as well as chemisorption
      time. Films prepared with PEO of molecular weight 750, 2000, and 5000 g/mol were
      studied. Chain densities determined in the dry state by ellipsometry were found
      to be in the range of 0.4-0.7, 0.33-0.58, and 0.12-0.30 chains/nm(2) for MW 750,
      2000, and 5000 PEO, respectively. Chain density was found to decrease with
      increasing molecular weight and to increase as cloud-point conditions were
      approached. PEO-layer mass densities and chain densities were determined
      independently by neutron reflectometry. Under low-solubility conditions and for a
      4-h chemisorption time, film mass and chain density values of 1.0 +/-0.3 g cm(-3)
      and 1.8 +/- 0.9 chains/nm(2) were found for MW 750 PEO, and 0.82 +/- 0.02 g cm(
      3) and 0.23 +/- 0.07 chains/nm(2) for MW 5000 PEO. Ellipsometry data for these
      systems yielded graft densities of 0.63 +/- 0.13 and 0.30 +/- 0.02 chains/nm(2),
      respectively. Using the mass densities obtained from the neutron data in the
      ellipsometry calculations, chain densities of 0.6 +/- 0.3 and 0.25 +/- 0.02
      chains/nm(2), respectively, were obtained for the MW 750 and 5000 films. The
      ellipsometry and neutron data for the MW 5000 system are thus in agreement within
      experimental error. In general, the chain-density values are much higher than
      those corresponding to layers of unperturbed random coil PEO ("mushrooms"),
      suggesting that the PEO layers are in the brush regime with the chains in an
      extended conformation.

PMID- 15567387
TI  - Improved cellular adhesion to acetone plasma modified polystyrene surfaces.
AB  - The plasma polymerization of acetone has been used to modify polystyrene
      substrates for the controlled growth of human fibroblast cells. The surface
      modified polystyrene was studied by X-ray photoelectron spectroscopy, water
      contact angle and atomic force microscopy. This showed the surface oxygen levels
      and wettability to increase rapidly with exposure to the acetone plasma. High
      resolution XPS allowed the determination of the relative amounts of surface
      hydroxyl, carbonyl and carboxyl groups. This showed that there was little
      incorporation of carboxyl groups in the deposited films. AFM measurements
      revealed the films to be conformal with a surface roughness equivalent to that of
      the underlying polystyrene substrate with film growth rates of approximately 0.5
      nm min(-1). High edge-definition patterns were produced with a simple masking
      procedure and allowed the confinement of cells to selected areas of the
      substrate. These chemically patterned surfaces allowed the study of cells
      confined to particular regions of the substrate as a function of incubation time.

PMID- 15567388
TI  - Dissolution kinetics of granular calcium carbonate in concentrated aqueous sodium
      dichromate solution at pH 6.0-7.0 and 110-130 degrees C.
AB  - An understanding of the factors controlling calcite dissolution is important for
      modeling geochemical cycles and impacts of greenhouse gases on climate,
      diagenesis of sediments, and sedimentary rocks. It also has practical
      significance in the investigation of behavior of carbonates in petroleum and
      natural gas reservoirs and in the preservation of buildings and monuments
      constructed from limestone and marble. A large number of papers have been
      published on dissolution kinetics of calcium carbonate in aqueous solutions. But
      few involved the near-equilibrium region, especially at elevated temperatures and
      in concentrated solutions. In this paper, the dissolution kinetics of calcium
      carbonate in concentrated aqueous sodium dichromate solutions at pH 6.0-7.0 and
      110-130 degrees C were studied in a 2-L autoclave. The results indicate that the
      dissolution reaction is mix-controlled, with surface reaction as the prevailing
      factor. The concentration of calcium ions in solution hardly affects the
      dissolution rate, but carbon dioxide in the vapor phase inhibits the dissolution
      reaction. The dissolution rate can be expressed by R = k(1)a(2)(H+) + k(2), and
      the apparent activation energy is 55-84 kJ mol(-1).

PMID- 15567389
TI  - Physicochemical properties and stability of activated sludge flocs under
      temperature upshifts from 30 to 45 degrees C.
AB  - The impacts of temperature shifts from 30 to 45 degrees C on the structural
      stability and surface charge of activated sludge flocs were assessed in four
      sequencing batch reactors (SBRs) treating pulp and paper mill effluent. The
      improvement in floc stability was tested by sludge magnesium enrichment in one
      SBR and by operating another reactor at a high sludge retention time (SRT) of 33
      days. Floc stability was characterized by dissociation constants with solutions
      of CaCl(2), KCl, urea, and ethylenediamine tetraacetate (EDTA). Surface charge
      was assessed by cationic-anionic titration and metals concentrations were also
      determined. The temperature shift consistently caused an increase in the negative
      sludge surface charge from approximately -0.180 to -0.300 meq/g MLSS. Magnesium
      enrichment and a high SRT of 33 days promoted less negatively charged sludge,
      dampened the increase in negative sludge surface charge, and yielded structurally
      stronger flocs; however, sludge deflocculation still occurred. Manganese and iron
      appeared to be released by sludge under the temperature shift. It was concluded
      that the temperature shift deteriorates the flocculating physicochemical
      properties of the sludge and that better floc stability achieved by magnesium
      enrichment and a high SRT is not enough to stop deflocculation. Further research
      is required to clarify the origin of the increase in negative sludge surface
      charge, the role of metals, and the governing factors in sludge deflocculation
      under such temperature shifts.

PMID- 15567390
TI  - Migration and precipitation of soluble species during drying of colloidal films.
AB  - The evaporation-induced convection resulted in a transport of dissolved species,
      a water-soluble polymer (carboxymethylcellulose) and dissolved CaCO(3), to the
      drying front of silica and CaCO(3) dispersions where the material eventually
      precipitates. Scanning electron microscopy and chemical analysis showed that the
      concentration of carboxymethylcellulose, CMC, is highest in the centre of the
      dried silica film and decreases towards the perifery. The colloidal films of the
      monodisperse silica particles displayed a high degree of structural order even at
      high concentrations of the non-adsorbed polymer CMC, which suggests that any
      depletion induced interparticle attraction is insufficient to affect the assembly
      of the colloidal crystal. The CaCO(3) particles are slightly soluble and we found
      that rod-like crystals reprecipitated in the centre of the particle films on top
      of the polyacrylate-coated particles. Addition of CMC disturbs the formation of
      distinct crystal shapes which was attributed to a complexation of Ca(2+) in
      solution.

PMID- 15567391
TI  - Adsorption of poly(acrylic acid) onto the surface of titanium dioxide and the
      colloidal stability of aqueous suspension.
AB  - The adsorption of poly(acrylic acid) (PAA) in aqueous suspension onto the surface
      of TiO(2) nanoparticles was investigated. FTIR spectroscopic data provided
      evidence in support of hydrogen bonding and chemical interaction in the case of
      the PAA-TiO(2) system. Adsorption isotherms demonstrated that part of the PAA
      initially added to the suspension was adsorbed onto the TiO(2) surface, after
      which there was a gradual attainment of an adsorption plateau. The adsorption
      density of PAA was found to increase with an increase of PAA molecular weight,
      while it decreased with an increase of pH. The thickness of the PAA adsorption
      layer was calculated based on measurements of suspension viscosities in the
      absence and presence of PAA. It was shown that the thickness of the adsorption
      layer increased with the increase of pH, PAA molecular weight, and its
      concentration. The surface charge density, the diffuse charge density, and the
      zeta potential of TiO(2) varied distinctly after PAA adsorption. The shift of
      pH(iep) toward a lower pH value was observed in the presence of PAA. PAA was
      found to stabilize the suspension of TiO(2) nanoparticles through electrosteric
      repulsion. The influence of factors such as PAA molecular weight and its
      concentration on the colloidal stability of the aqueous suspension was also
      investigated.

PMID- 15567392
TI  - Bimetallic isopropoxides M[Al(OC(3)H(i)(7))(4)](3) (M = Pr, Nd)--catalyzed
      reduction of 2-octanone and benzophenone.
AB  - Bimetallic alkoxides of praseodymium and neodymium with aluminum, viz.,
      M[Al(OC(3)H(i)(7))(4)](3), where M = Pr(III)/Nd(III), have been used as catalysts
      in Meerwein-Ponndorf-Verley (MPV) reduction of 2-octanone and benzophenone in
      isopropanol to give their corresponding secondary alcohols. The reduction of
      ketones is investigated by following the absorption spectra involving 4f-4f
      transitions. During the MPV reduction the oscillator strengths (P) and the Judd
      Ofelt intensity (T(lambda), lambda = 2,4,6) parameters corresponding to each 4f
      4f band (H43-->D21, H43-->P03, H43-->P13, and H43-->P23 in praseodymium, and
      I9/24-->F3/24, I9/24-->F5/24, I9/24-->F7/24, I9/24-->G5/24, and I9/24-->G7/24 in
      neodymium alkoxides) at different time intervals have also been calculated and
      used in the determination of rates. Rates were calculated in terms of
      complexation of ketone and isopropanol with M[Al(OC(3)H(i)(7))(4)](3) during the
      MPV reaction, from the changes in both absorbance and oscillator strength with
      time, and were found to be comparable, verifying the Judd-Ofelt theory. The
      stronger oxyphilicity of Pr(III) and Nd(III) in M[Al(OC(3)H(i)(7))(4)](3) than of
      their analogue Al(III) in Al(OC(3)H(i)(7))(3) made the bimetallic alkoxides
      better catalyst in MPV reduction of ketones.

PMID- 15567393
TI  - Adsorption of NO and CO over transition-metal-incorporated mesoporous catalytic
      materials.
AB  - Novel high-surface-area mesoporous catalysts of type Al-MCM-41 containing
      transition metals such as iron, nickel, cobalt, zinc, copper, and cobalt were
      prepared and characterized using techniques such as BET, FTIR, ICP-MS, XPS, and
      XRD. The XPS measurements indicated that the transition-metal particles are
      located in the bulk or pore channels of the Al-MCM-41 materials. A detailed in
      situ FTIR investigation undertaken on the adsorption and disproportionation of NO
      and CO over the transition-metal-Al-MCM-41 mesoporous catalysts indicated the
      formation of various NO/CO species or complexes with active metal sites. The
      structure and dynamics of the metal activated complex and reactive species formed
      during the CO/NO reaction together with advantages of these catalysts and the
      influence of reaction temperature and pressure have been studied. NO adsorption
      at room temperature leads to the formation of adsorbed N(2)O, NO(2), MNO(2), MNO,
      and [M(NO)(2)] complexes. CO adsorption at room temperature leads to the
      formation of physisorbed carbon dioxide and cationic Lewis acid carbonyl moieties
      as well as transition-metal carbonyl complexes. The copper mesoporous catalysts
      prepared by different procedures (ion exchanged and as-synthesized) were compared
      for their interactions with CO and NO probe molecules.

PMID- 15567394
TI  - Modification of ion-exchange membrane used for separation of protons and metallic
      cations and characterization of the membrane by current-voltage curves.
AB  - The ionic transport properties of several cations (H(+), Na(+), and Zn(2+))
      across sulfonated ion-exchange membranes modified with an amine were investigated
      by the measurement of current-voltage curves to determine the effect of the
      surface modification of the membrane. The membrane was modified by
      chlorosulfonation and amination with a diamine (N,N-dimethylethylenediamine) and
      an amine (isoamylamine) to form a sulfonamide bond between amine groups and the
      surface layer. In the case of the modification with the diamine, the terminal
      amine was protonated in acidic media or quaternized with methyl iodide. The
      presence of a positively charged layer on the two sides of the membrane strongly
      decreased the limiting current flowing across the membrane in the presence of a
      1:1 electrolyte such as HCl or HNO(3) due to an increase of the resistance of the
      membrane. In the case of divalent cations such as Na(+) and Zn(2+), electrostatic
      repulsion also contributes to the decrease of the limiting current. The presence
      of divalent anions seems to increase the limiting current somewhat due to their
      preconcentration within the cationic layer, which facilitates their subsequent
      transport across the membrane. When only one face of the membrane was modified,
      the current-voltage measurements showed that the membrane did not behave like a
      bipolar membrane. For one-side (under forward polarization) and two-side modified
      membranes, counterions are slightly blocked in the membrane by the cationic
      layer, which led to a decrease of the membrane conductivity during
      electrodialysis.

PMID- 15567395
TI  - Effect of calcium and carbonate concentrations on cationic membrane fouling
      during electrodialysis.
AB  - Fouling, which is the accumulation of undesired solid materials at the phase
      interfaces of permselective membranes, is one of the major problems in
      electrodialysis. The aim of the present work was to investigate the effect on the
      fouling of cation-exchange membranes of the composition in calcium and carbonate
      of a model solution to be treated by electrodialysis. No fouling was observed at
      400 and 800 mg/L of CaCl(2) in the absence of carbonate, while at only 400 mg/L
      CaCl(2) with carbonate, a deposit was observed. This difference could be
      explained by the buffering capacity of the carbonate, which affects the treatment
      duration with and without sodium carbonate. Since the duration was longer with
      carbonate, more calcium ions were able to migrate across the CMX-S membrane,
      which explained the higher deposit on its surface. Furthermore, whether there was
      carbonate in the solution treated by electrodialysis or not, the deposit on the
      surface of the cationic membrane was calcium hydroxide. However, this fouling
      formed during conventional ED was easily cleaned by an acid procedure.

PMID- 15567396
TI  - Solid base for hydrogen sulfide removal in light oil.
AB  - Three solid bases, with three kinds of activated carbon as supporters and
      alkaline materials as active components, were tested for hydrogen sulfide removal
      in light oil. The solid bases have high intensity and greater adsorption capacity
      for hydrogen sulfide removal and are more easily regenerated.

PMID- 15567397
TI  - Observation of wall wettability under imposed flow by fluorescence
      depolarization: dependence on surface oxygen content and degree of polymer
      branching.
AB  - This work was concerned with the dependence of the interfacial tension
      (Gamma(SL)) on surface degree of oxygen content and on polymer branching degree.
      The static Gamma(SL) was evaluated by contact angle (theta;(c)) and the dynamic
      Gamma(SL) by fluorescence depolarization of molecular probes seeded in induced
      flows of monoethylene glycol. The latter results were interpreted using
      statistical covariant analysis. Two different systems of flowing films were
      studied: free films flowing on the surfaces on which they impinge and films
      flowing inside 1-mm-thick microflow cells. The solid surfaces were polyethylene
      of low density, medium density, high density, and linear with low density,
      polypropylene, vinyl acetate co-polymer with oxygen content of 15% and 28%,
      borosilicate, and tin dioxide. Increase in oxygen content of the surface
      decreased both the static and the dynamic Gamma(SL), which demonstrated that the
      presence of oxygen atoms hindered wetting. Only the dynamical Gamma(SL) was
      sensitive to polymer branching, and it increased as branching degree decreased.
      This was attributed to the higher hydrogen-atom density at the surface, which
      favored temporary intermolecular bonds between the surface and the flowing
      liquid.

PMID- 15567398
TI  - Energy and hydrodynamic approaches to magnetocapillary instability of
      nonconducting jets.
AB  - The field energy and magnetocapillary instability of isothermal incompressible
      and inviscid nonconducting liquid jets in a uniform magnetic field are
      considered. The equivalence between static and dynamic approaches at the onset of
      instability and cutoff wavelength is shown and its implications are discussed. A
      new dispersion relation for magnetocapillary instability in such jets is derived.
      This relation differs from that given in the literature. The existence of a
      critical magnetic field that stabilizes jets with finite susceptibility is
      established. It is shown that the jet is stabilized by the field irrespective of
      its being para- or diamagnetic, but the extent of stabilization is different.

PMID- 15567399
TI  - Interactions between n-octyl and n-nonyl beta-D-glucosides and alpha- and beta
      cyclodextrins as seen by self-diffusion NMR.
AB  - In this work (1)H NMR self-diffusion experiments have been performed to determine
      the self-diffusion coefficients of n-octyl beta-d-glucoside and n-nonyl beta-d
      glucoside in alpha-cyclodextrin and beta-cyclodextrin solutions at 25 degrees C.
      Two questions are addressed. The first concerns the general influence on nonionic
      surfactant transport properties when cyclodextrins are present in solution. The
      second question concerns the influence of surfactant-chain length and
      cyclodextrin cavity volume on the association constant. The self-diffusion
      coefficients of the alkyl glucosides, in cyclodextrin-containing solutions,
      depend on the cyclodextrin concentration on account of the formation of
      complexes. The cyclodextrin diffusion is only mildly influenced, since the
      complex has similar diffusion coefficients as the free cyclodextrin. There are
      some obstruction effects at the highest surfactant concentrations which decrease
      the cyclodextrin diffusion. A set of equations to model the self-diffusion
      coefficients of the surfactant and cyclodextrin was developed and is presented.
      On the basis of such equations, properties such as association constants, and
      micelle and complex diffusion coefficients can be estimated.

PMID- 15567400
TI  - Effect of microwave pretreatment of coal for improvement of rheological
      characteristics of coal-water slurries.
AB  - Indian high-ash coal contains alpha-silica components of the mineral matter. When
      coal is transported in the form of a slurry, alpha-silica adds to the settling
      properties of coal and enhances erosion of pipelines. As such any technique that
      will contribute to changing the characteristics of mineral matter by selective
      demineralization is bound to supplement the knowledge of coal slurries in the
      science of rheology. One such method is the use of a novel microwave technology,
      which changes the alpha-silica to less harmful beta-silica. Thus microwave
      treated coal slurry facilitates enhanced flow characteristics and abates the
      erosion problem in pipeline transport as well as in coal-slurry injection
      furnaces. This paper reports on the rheological study of closely sized coal
      particles of medium-volatile, low-ash, low-moisture cleans and high-ash rejects
      with and without microwave treatment. Viscosity of suspensions of microwave
      treated coal was found to be less than that of untreated coal, in the case of
      both cleans and rejects. Microwave pretreatment thus reduces the viscosity and
      the pumping cost and opens a new outlook for pipeline transport. An attempt has
      been made to quantify the improvement of rheological characteristics due to
      microwave pretreatment.

PMID- 15567401
TI  - An oscillating electric field with thermal noise increases the rotational
      diffusion and drives rotation in a dipole.
AB  - Here we consider a dipole in a viscous medium under the influence of an
      oscillating electric field and thermal noise. Because of the very low Reynolds
      numbers involved in molecular processes, we considered overdamped Langevin
      dynamics. As a consequence the inertia term becomes negligible. We observed a
      great increase in the rotational diffusion and also net rotation for some values
      of the parameters.

PMID- 15567402
TI  - Electrokinetic properties of sepiolite suspensions in different electrolyte
      media.
AB  - The present paper deals with the electrokinetic characterization of sepiolite. A
      series of systematic zeta potential measurements have been carried out to
      determine the isoelectric point (iep) and potential-determining ions (pdi), and
      the effect of mono-, di-, and trivalent electrolytes such as NaCl, KCl, LiCl,
      NaNO(3), NaCH(3)COO, MgCl(2), CaCl(2), BaCl(2), CoCl(2), CuCl(2), Pb(NO(3))(2),
      Na(2)CO(3), Na(2)SO(4), AlCl(3), FeCl(3), and Na(3)PO(4) on the zeta potential of
      sepiolite. Zeta potential has been calculated with the aid of Smoluchowski's
      equation. Sepiolite yields an isoelectric point at pH 6.6. The zeta potential for
      the sepiolite has ranged from +23.3 mV at pH approximately 2 to -22.4 mV at pH
      approximately 8 at 20 +/- 2 degrees C in water. The valency of the ions have
      proven to have a great influence on the electrokinetic behavior of the
      suspension. Monovalent cations were found to have a weak effect, while di- and
      trivalent cations made the zeta potential positive. Charge reversal was observed
      for divalent cations at 1 x 10(-2) M and for trivalent cations at 3 x 10(-4) M.
      As a result, it can be said that monovalent cations are indifferent ions when di-
      and trivalent cations are potential-determining ions.

PMID- 15567403
TI  - Soap-free synthesis for producing highly monodisperse, micrometer-sized
      polystyrene particles up to 6 microm.
AB  - A soap-free emulsion polymerization method with the use of an amphoteric
      initiator, currently proposed by the authors for producing highly monodisperse,
      micrometer-sized polymer particles, was examined in the polymerization of styrene
      with a 2,2'-azobis [N-(2-carboxyethyl)-2-2-methylpropionamidine] hydrate
      initiator and an NH(4)OH/NH(4)Cl pH buffer. The pH buffer was used to control the
      electric surface potential of particles to maintain a stable dispersion of
      particles and to prevent generation of new particles during the polymerization.
      Addition of monomer to the reaction system during polymerization could enlarge
      the average size of polymer particles to 5.7 microm with a coefficient of
      variation of 1.5%, which is much less than the standard criteria of
      monodispersity, 10%.

PMID- 15567404
TI  - Chemical remediation of beech condensates.
AB  - In the present work, beech wood condensates are separated from the aqueous phase.
      Experimental results reveal an electrostatic interaction between the oppositely
      charged wood extracts after oxidation and Ca(OH)(2). The increase in aqueous
      phase pH resulted in enhanced removal of wood extracts from water. The
      polarographic assays were carried out at 25 degrees C using a Gilson oxygraph
      equipped with a Clark electrode in order to determine the oxygen uptake during
      the oxidation reaction. The effect of pH is explained based on oxygen uptake. The
      organic compounds found in the aqueous effluent are responsible for the brown
      color. The objective of this study is to find the optimum pH to eliminate the
      wood extracts from the liquid effluents.

PMID- 15567405
TI  - Analytical expressions for the electrical potential near planar, cylindrical, and
      spherical surfaces for symmetric electrolytes.
AB  - The conjecture of Tuinier (J. Colloid Interface Sci. 258 (2003) 45) for the
      electrical potentials near a cylindrical surface and near a spherical surface
      under the conditions of symmetric electrolyte and large scaled radius are derived
      by solving the corresponding Poisson-Boltzmann equation. The surface charge
      density-surface potential relations for these surfaces are also derived under the
      conditions of constant surface potential. We show that the level of surface
      charge density for planar, cylindrical, and spherical surfaces follows the order
      spherical surface > cylindrical surface > planar surface.

PMID- 15567406
TI  - Structural and evolutionary division of phosphotyrosine binding (PTB) domains.
AB  - Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or
      scaffolds to organize the signaling complexes involved in wide-ranging
      physiological processes including neural development, immunity, tissue
      homeostasis and cell growth. There are more than 200 proteins in eukaryotes and
      nearly 60 human proteins having PTB domains. Six PTB domain encoded proteins have
      been found to have mutations that contribute to inherited human diseases
      including familial stroke, hypercholesteremia, coronary artery disease,
      Alzheimer's disease and diabetes, demonstrating the importance of PTB scaffold
      proteins in organizing critical signaling complexes. PTB domains bind both
      peptides and headgroups of phosphatidylinositides, utilizing two distinct binding
      motifs to mediate spatial organization and localization within cells. The
      structure of PTB domains confers specificity for binding peptides having a NPXY
      motif with differing requirements for phosphorylation of the tyrosine within this
      recognition sequence. In this review, we use structural, evolutionary and
      functional analysis to divide PTB domains into three groups represented by
      phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like and
      phosphotyrosine-independent Dab-like PTBs, with the Dab-like PTB domains
      representing nearly 75% of proteins encoding PTB domains. In addition, we further
      define the binding characteristics of the cognate ligands for each group of PTB
      domains. The signaling complexes organized by PTB domain encoded proteins are
      largely unknown and represents an important challenge in systems biology for the
      future.

PMID- 15567407
TI  - Structural characterization of the Ser324Thr variant of the catalase-peroxidase
      (KatG) from Burkholderia pseudomallei.
AB  - The Ser315Thr variant of the catalase-peroxidase KatG from Mycobacterium
      tuberculosis imparts resistance to the pro-drug isonicotinic acid hydrazide
      (isoniazid) through a failure to convert it to the active drug, isonicotinoyl
      NAD. The equivalent variant in KatG from Burkholderia pseudomallei, Ser324Thr,
      has been constructed, revealing catalase and peroxidase activities that are
      similar to those of the native enzyme. The other activities of the variant
      protein, including the NADH oxidase, the isoniazid hydrazinolysis and
      isonicotinoyl-NAD synthase activities are reduced by 60-70%. The crystal
      structure of the variant differs from that of the native enzyme in having the
      methyl group of Thr324 situated in the entrance channel to the heme cavity, in a
      modified water matrix in the entrance channel and heme cavity, in lacking the
      putative perhydroxy modification on the heme, in the multiple locations of a few
      side-chains, and in the presence of an apparent perhydroxy modification on the
      indole nitrogen atom of the active-site Trp111. The position of the methyl group
      of Thr324 creates a constriction or narrowing of the channel leading to the heme
      cavity, providing an explanation for the lower reactivity towards isoniazid and
      the slower rate of isonicotinoyl-NAD synthesis.

PMID- 15567408
TI  - X-ray structural studies of Mycobacterium tuberculosis RRF and a comparative
      study of RRFs of known structure. Molecular plasticity and biological
      implications.
AB  - The crystal structure of Mycobacterium tuberculosis ribosome recycling factor has
      been determined and refined against three X-ray diffraction data sets, two
      collected at room temperature and the other at 100K. The two room-temperature
      data sets differ in the radiation damage suffered by the crystals before the data
      used for processing were collected. A comparison between the structures refined
      against the two data sets indicates the possibility of radiation-induced
      conformational change. The L-shaped molecule is composed of a long three-helix
      bundle domain (domain I) and a globular domain (domain II) connected by a linker
      region. The main difference between the room-temperature structure and the low
      temperature structure is in the rotation of domain II about an axis close to its
      libration axis. This observation and a detailed comparative study of ribosome
      recycling factors (RRFs) of known structures led to an elaboration of the present
      understanding of the structural variability of RRF. The variability involves a
      change in the angle between the two arms of the molecule, a rotation of domain II
      in a plane nearly perpendicular to the axis of the helix bundle and an internal
      rotation of domain II. Furthermore, the domains and the linker could be
      delineated into fixed and variable regions in a physically meaningful manner. The
      relative mobility of the domains of the molecule in the crystal structure appears
      to be similar to that in the ribosome--RRF complex. That permits a meaningful
      discussion of the structural features of RRF in terms of ribosome--RRF
      interactions. The structure also provides insights into the results of inter
      species complementation studies.

PMID- 15567409
TI  - P-site pairing subtleties revealed by the effects of different tRNAs on
      programmed translational bypassing where anticodon re-pairing to mRNA is
      separated from dissociation.
AB  - Programmed ribosomal bypassing occurs in decoding phage T4 gene 60 mRNA. Half the
      ribosomes bypass a 50 nucleotide gap between codons 46 and 47. Peptidyl-tRNA
      dissociates from the "take-off" GGA, codon 46, and re-pairs to mRNA at a matched
      GGA "landing site" codon directly 5' of codon 47 where translation resumes. The
      system described here allows the contribution of peptidyl-tRNA re-pairing to be
      measured independently of dissociation. The matched GGA codons have been replaced
      by 62 other matched codons, giving a wide range of bypassing efficiencies. Codons
      with G or C in either or both of the first two codon positions yielded high
      levels of bypassing. The results are compared with those from a complementary
      study of non-programmed bypassing, where the combined effects of peptidyl-tRNA
      dissociation and reassociation were measured. The wild-type, GGA, matched codons
      are the most efficient in their gene 60 context in contrast to the relatively low
      value in the non-programmed bypassing study.

PMID- 15567410
TI  - Structural analysis of the group II intron splicing factor CRS2 yields insights
      into its protein and RNA interaction surfaces.
AB  - Chloroplast RNA splicing 2 (CRS2) is a nuclear-encoded protein required for the
      splicing of nine group II introns in maize chloroplasts. CRS2 functions in the
      context of splicing complexes that include one of two CRS2-associated factors
      (CAF1 and CAF2). The CRS2-CAF1 and CRS2-CAF2 complexes are required for the
      splicing of different subsets of CRS2-dependent introns, and they bind tightly
      and specifically to their genetically defined intron targets in vivo. The CRS2
      amino acid sequence is closely related to those of bacterial peptidyl-tRNA
      hydrolases (PTHs). To identify the structural differences between CRS2 and
      bacterial PTHs responsible for CRS2's gains of CAF binding and intron splicing
      functions, we determined the structure of CRS2 by X-ray crystallography. The fold
      of CRS2 is the same as that of Escherichia coli PTH, but CRS2 has two surfaces
      that differ from the corresponding surfaces in PTH. One of these is more
      hydrophobic in CRS2 than in PTH. Site-directed mutagenesis of this surface
      blocked CRS2-CAF complex formation, indicating that it is the CAF binding site.
      The CRS2 surface corresponding to the putative tRNA binding face of PTH is
      considerably more basic than in PTH, suggesting that CRS2 interacts with group II
      intron substrates via this surface. Both the sequence and the structural context
      of the amino acid residues essential for peptidyl-tRNA hydrolase activity are
      conserved in CRS2, yet expression of CRS2 is incapable of rescuing a
      pth(ts)E.coli strain.

PMID- 15567411
TI  - Untying the FIV frameshifting pseudoknot structure by MS3D.
AB  - The structure of the putative feline immunodeficiency virus (FIV) ribosomal
      frameshifting pseudoknot (PK) has been investigated by a mass spectrometric three
      dimensional (MS3D) approach, which involves the application of established
      solvent-accessibility probes and chemical crosslinkers with detection by
      electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS).
      Regardless of their size, probed substrates can be treated with ribonucleases and
      analyzed by ESI-FTMS to obtain the correct position of chemically modified
      nucleotides. Protection maps and distance information can be utilized to generate
      3D models using the constraint satisfaction algorithm provided by MC-SYM and the
      energy minimization modules included in CNS. Control experiments were performed
      on a mutant of mouse mammary tumor virus pseudoknot (VPK), for which an NMR
      structure is available. Comparison between the MS3D model and the high-resolution
      structure provided a approximately 3A root-mean-square deviation calculated from
      all the atoms present in double-stranded regions. Applied to FIV-PK, the MS3D
      approach confirmed that the selected sequence could fold into an actual
      pseudoknot, supporting the sequence alignment predictions. Characteristic
      features of H-type pseudoknots were recognized immediately, but a putative A13
      U30 pair was not observed at the stem junction, making FIV-PK resemble VPK more
      closely than the initially suggested simian retrovirus type-1 pseudoknot. In our
      model, the unpaired U30 protrudes into the medium, while the hinging A13 assumes
      a stacked conformation that enables the stems to form a approximately 60 degrees
      bend and relieve the strain caused by a short loop 1. The model provided the
      basis to explain the different alkylation patterns observed in the absence and
      presence of Mg(2+), suggesting the possible formation of a specific metal-binding
      site between loop 1 and stem 2. This instance illustrates how the MS3D model of
      FIV-PK can be utilized effectively to generate hypotheses and support functional
      observations in the absence of a high-resolution structure.

PMID- 15567412
TI  - Mechanism of PKR activation: dimerization and kinase activation in the absence of
      double-stranded RNA.
AB  - The kinase PKR is a central component of the interferon antiviral pathway. PKR is
      activated upon binding double-stranded (ds) RNA to undergo autophosphorylation.
      Although PKR is known to dimerize, the relationship between dimerization and
      activation remains unclear. Here, we directly characterize dimerization of PKR in
      free solution using analytical ultracentrifugation and correlate self-association
      with autophosphorylation activity. Latent, unphosphorylated PKR exists
      predominantly as a monomer at protein concentrations below 2 mg/ml. A monomer
      sedimentation coefficient of s(20,w)(0)=3.58 S and a frictional ratio of
      f/f(0)=1.62 indicate an asymmetric shape. Sedimentation equilibrium measurements
      indicate that PKR undergoes a weak, reversible monomer-dimer equilibrium with
      K(d)=450 microM. This dimerization reaction serves to initiate a previously
      unrecognized dsRNA-independent autophosphorylation reaction. The resulting
      activated enzyme is phosphorylated on the two critical threonine residues present
      in the activation loop and is competent to phosphorylate the physiological
      substrate, eIF2alpha. Dimer stability is enhanced by approximately 500-fold upon
      autophosphorylation. We propose a chain reaction model for PKR dsRNA-independent
      activation where dimerization of latent enzyme followed by intermolecular
      phosphorylation serves as the initiation step. Subsequent propagation steps
      likely involve phosphorylation of latent PKR monomers by activated enzyme within
      high-affinity heterodimers. Our results support a model whereby dsRNA functions
      by bringing PKR monomers into close proximity in a manner that is analogous to
      the dimerization of free PKR.

PMID- 15567413
TI  - Mechanism of recruitment of class II histone deacetylases by myocyte enhancer
      factor-2.
AB  - Class II histone deacetylases (HDACs) bind myocyte enhancer factor-2 (MEF2) and
      repress specific gene expression in a calcium-dependent manner. Despite their
      significant physiological functions in muscle, immune and neuronal cells, the
      mechanism of recruitment of class II HDACs by MEF2 is not well understood. Here,
      we have characterized the complex between the MEF2-binding motif of class II
      HDACs and the MADS-box/MEF2S domain of MEF2B by structural and biochemical
      methods. The crystal structure of a HDAC9/MEF2/DNA complex reveals that HDAC9
      binds to a hydrophobic groove of the MEF2 dimer. The overall binding mode is
      similar to that seen in the Cabin1/MEF2/DNA complex. The detailed binding
      interactions at the HDAC9/MEF2 interface, however, show marked differences from
      those at the Cabin1/MEF2 interface. Our studies suggest a general mechanism by
      which class II HDACs and possibly other transcriptional co-regulators are
      recruited by MEF2. On the other hand, the differential binding between MEF2 and
      its various partners may confer specific regulatory and functional properties to
      MEF2 in distinct cellular processes. Such specificity provides a basis for
      selectively disrupting a particular MEF2/co-regulator complex by mutations or
      small molecules.

PMID- 15567414
TI  - Nucleosomes in solution exist as a mixture of twist-defect states.
AB  - The 2.0 A crystal structure of a nucleosome core particle in complex with a
      bivalent pyrrole-imidazole polyamide reveals that this "clamp" effectively
      crossbraces the two gyres of the DNA superhelix, thereby stabilizing the
      nucleosome against dissociation. Using X-ray crystallography and footprinting
      techniques, we show that the clamp preferentially binds nucleosomes over free
      DNA, and that nucleosomal DNA exists as a mixture of multiple twist-defect
      intermediates in solution. The nucleosomes exist in one of two different
      conformations in various crystal structures that trap twist-defect intermediates,
      even on a strong positioning sequence. Evidence has been obtained supporting the
      existence of twist-defect states in nucleosomal DNA in solution that are similar
      to those obtained in crystal structures. Our results also substantiate the idea
      that twist diffusion may represent an important means of altering the
      accessibility of nucleosomal DNA both in the presence and in the absence of ATP
      dependent chromatin-remodelling enzymes.

PMID- 15567415
TI  - The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase
      in a ternary complex with the antimalarial compound fosmidomycin and NADPH
      reveals a tight-binding closed enzyme conformation.
AB  - The key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis, 1-deoxy
      D-xylulose 5-phosphate reductoisomerase (DXR) has been shown to be the target
      enzyme of fosmidomycin, an antimalarial, antibacterial and herbicidal compound.
      Here we report the crystal structure of selenomethionine-labelled Escherichia
      coli DXR in a ternary complex with NADPH and fosmidomycin at 2.2 A resolution.
      The structure reveals a considerable conformational rearrangement upon
      fosmidomycin binding and provides insights into the slow, tight binding
      inhibition mode of the inhibitor. Although the inhibitor displays an unusual non
      metal mediated mode of inhibition, which is an artefact most likely due to the
      low metal affinity of DXR at the pH used for crystallization, the structural data
      add valuable information for the rational design of novel DXR inhibitors. Using
      this structure together with the published structural data and the 1.9 A crystal
      structure of DXR in a ternary complex with NADPH and the substrate 1-deoxy-D
      xylulose 5-phosphate, a model for the physiologically relevant tight-binding mode
      of inhibition is proposed. The structure of the substrate complex must be
      interpreted with caution due to the presence of a second diastereomer in the
      active site.

PMID- 15567416
TI  - Structural requirements and mechanism for heparin-dependent activation and
      tetramerization of human betaI- and betaII-tryptase.
AB  - Tryptase, a tetrameric serine protease, is a main constituent of the secretory
      granules in human mast cells, where it is stored in complex with heparin or
      chondroitin sulfate proteoglycan. Human tryptase has been implicated in a variety
      of clinical conditions including asthma, but the mechanisms that lead to its
      tetramerization/activation have not been extensively investigated. Here we
      addressed the activation mechanisms for human betaI and betaII-tryptase, which
      differ in that betaI-tryptase is N-glycosylated at Asn102 whereas betaII-tryptase
      has a Lys residue at position 102, and consequently lacks the corresponding N
      glycosylation. We found that both tryptases were dependent on heparin for
      activation/tetramerization, but whereas betaI-tryptase activation preferentially
      occurred at acidic pH, betaII-tryptase activation was less pH-dependent. Both
      betaI and betaII-tryptase bound strongly to heparin-Sepharose at acidic pH but
      with lower affinity at neutral pH. Further, while addition of heparin to betaI
      tryptase predominantly resulted in formation of active tetrameric enzyme, betaII
      tryptase showed a tendency to form inactive aggregates. betaI and betaII-tryptase
      were similar in that the minimal heparin size to induce activation was an
      octasaccharide and in that the interaction with heparin and structurally related
      polysaccharides was dependent on high anionic charge density rather than on
      specific structural motifs. Addition of decasaccharides to both betaI and betaII
      tryptase resulted in the formation of active monomeric enzyme, whereas intact
      heparin promoted assembly of tetrameric enzyme. This, together with a bell-shaped
      dose response curve for heparin-induced activation, suggests that the mechanism
      for tetramerization involves bridging of individual tryptase monomers by heparin.
      Taken together, this study indicates a key role for heparin in the activation of
      human beta-tryptase.

PMID- 15567417
TI  - Structure of a complex between Nedd8 and the Ulp/Senp protease family member
      Den1.
AB  - The Nedd8 conjugation pathway is conserved from yeast to humans and is essential
      in many organisms. Nedd8 is conjugated to cullin proteins in a process that
      alters SCF E3 ubiquitin ligase activity, and it is presumed that Nedd8
      deconjugation would reverse these effects. We now report the X-ray structures of
      the human Nedd8-specific protease, Den1, in a complex with the inhibitor Nedd8
      aldehyde, thus revealing a model for the tetrahedral transition state
      intermediate generated during proteolysis. Although Den1 is closely related to
      the SUMO-specific protease family (Ulp/Senp family), structural analysis of the
      interface suggests determinants involved in Nedd8 selectivity by Den1 over other
      ubiquitin-like family members and suggests how the Ulp/Senp architecture has been
      modified to interact with different ubiquitin-like modifiers.

PMID- 15567418
TI  - Molecular basis for the effect of urea and guanidinium chloride on the dynamics
      of unfolded polypeptide chains.
AB  - Chemical denaturants are frequently used to unfold proteins and to characterize
      mechanisms and transition states of protein folding reactions. The molecular
      basis of the effect of urea and guanidinium chloride (GdmCl) on polypeptide
      chains is still not well understood. Models for denaturant--protein interaction
      include both direct binding and indirect changes in solvent properties. Here we
      report studies on the effect of urea and GdmCl on the rate constants (k(c)) of
      end-to-end diffusion in unstructured poly(glycine-serine) chains of different
      length. Urea and GdmCl both lead to a linear decrease of lnk(c) with denaturant
      concentration, as observed for the rate constants for protein folding. This
      suggests that the effect of denaturants on chain dynamics significantly
      contributes to the denaturant-dependence of folding rate constants for small
      proteins. We show that this linear dependency is the result of two additive non
      linear effects, namely increased solvent viscosity and denaturant binding. The
      contribution from denaturant binding can be quantitatively described by
      Schellman's weak binding model with binding constants (K) of 0.62(+/-0.01)M(-1)
      for GdmCl and 0.26(+/-0.01)M(-1) for urea. In our model peptides the number of
      binding sites and the effect of a bound denaturant molecule on chain dynamics is
      identical for urea and GdmCl. The results further identify the polypeptide
      backbone as the major denaturant binding site and give an upper limit of a few
      nanoseconds for residence times of denaturant molecules on the polypeptide chain.

PMID- 15567419
TI  - Analysis of the pH-dependent folding and stability of histidine point mutants
      allows characterization of the denatured state and transition state for protein
      folding.
AB  - pH-Dependent studies of the folding kinetics and stability of a set of His to Gln
      point mutants were used to characterize the denatured state and transition state
      ensembles for the C-terminal domain of the ribosomal protein L9 (CTL9). CTL9
      contains three histidine residues, two of which, H106 and H134, are buried in the
      native state, while the third, H144, is more exposed. Comparison of the pH
      dependent stability calculated using the Tanford-Wyman linkage relationship to
      the measured values demonstrates that the apparent pK(a) values of the three
      histidine residues are not significantly perturbed in the denatured state
      ensemble. Kinetic measurements show that mutation of H134 has a larger effect on
      the folding process than does mutation of H106 and H144. The Phi-value for H134
      is significantly larger than the Phi-values for the other histidine residues,
      which are near zero at both pH 5.45 and pH 8.0. The Phi-value for H134 is higher,
      0.55, at pH 8.0 than at pH 5.45, 0.39. At pH 5.45, H134 is protonated in the
      unfolded state but deprotonated in the native state, while at pH 8.0 it is
      deprotonated in both. There is an excellent linear relationship between stability
      (logK) and folding rates (logk(f)) over the range of pH 5-9 for all mutants. From
      these plots, the ratio of DeltaQ( not equal)/DeltaQ can be calculated for each
      mutant. DeltaQ( not equal) is the difference in the number of protons bound to
      the transition state and to the unfolded state, while DeltaQ represents the
      difference between folded and denatured state. The linear plots indicate that the
      relative position of the transition state ensemble as judged by DeltaQ( not
      equal)/DeltaQ is independent of pH. The linkage analysis is consistent with the
      Phi-value analysis, showing that H134 is the most critical contributor to the
      development of pH-dependent interactions, including desolvation effects in the
      transition state ensemble.

PMID- 15567420
TI  - Amino acid requirements for formation of the TGF-beta-latent TGF-beta binding
      protein complexes.
AB  - Transforming growth factor beta (TGF-beta) is secreted primarily as a latent
      complex consisting of the TGF-beta homodimer, the TGF-beta propeptides (called
      the latency-associated protein or LAP) and the latent TGF-beta binding protein
      (LTBP). Mature TGF-beta remains associated with LAP by non-covalent interactions
      that block TGF-beta from binding to its receptor. Complex formation between LAP
      and LTBP is mediated by an intramolecular disulfide exchange between the third 8
      cysteine (8-Cys3) domain of LTBP with a pair of cysteine residues in LAP. Only
      the third 8-Cys domains of LTBP-1, -3, and -4 bind LAP. From comparison of the 8
      Cys3(LTBP-1) structure with that of the non-TGF-beta-binding 8-Cys6(fibrillin-1),
      we observed that a two-residue insertion in 8-Cys3(LTBP-1) increased the
      potential for disulfide exchange of the 2-6 disulfide bond. We further proposed
      that five negatively charged amino acid residues surrounding this bond mediate
      initial protein-protein association. To validate this hypothesis, we monitored
      binding by fluorescence resonance energy transfer (FRET) analysis and co
      expression assays with TGF-beta1 LAP (LAP-1) and wild-type and mutant 8-Cys3
      domains. FRET experiments demonstrated ionic interactions between LAP-1 and 8
      Cys3. Mutation of the five amino acid residues revealed that efficient complex
      formation is most dependent on two of these residues. Although 8-Cys3(LTBP-1)
      binds proTGF-betas effectively, the domain from LTBP-4 does so poorly. We
      speculated that this difference was due to the substitution of three acidic
      residues by alanine, serine, and arginine in the LTBP-4 sequence. Additional
      experiments with 8-Cys3(LTBP-4) indicated that enhanced binding of LAP to 8
      Cys3(LTBP-4) is achieved if the residues A, S, and R are changed to those in 8
      Cys3(LTBP1) (D, D, and E) and the QQ dipeptide insertion of LTBP-4 is changed to
      the FP in 8-Cys3(LTBP-1). These studies identify surface residues that contribute
      to the interactions of 8-Cys3 and LAP-1 and may yield information germane to the
      interaction of 8-Cys domains and additional TGF-beta superfamily propeptides, an
      emerging paradigm for growth factor regulation.

PMID- 15567421
TI  - Predicting enzyme class from protein structure without alignments.
AB  - Methods for predicting protein function from structure are becoming more
      important as the rate at which structures are solved increases more rapidly than
      experimental knowledge. As a result, protein structures now frequently lack
      functional annotations. The majority of methods for predicting protein function
      are reliant upon identifying a similar protein and transferring its annotations
      to the query protein. This method fails when a similar protein cannot be
      identified, or when any similar proteins identified also lack reliable
      annotations. Here, we describe a method that can assign function from structure
      without the use of algorithms reliant upon alignments. Using simple attributes
      that can be calculated from any crystal structure, such as secondary structure
      content, amino acid propensities, surface properties and ligands, we describe
      each enzyme in a non-redundant set. The set is split according to Enzyme
      Classification (EC) number. We combine the predictions of one-class versus one
      class support vector machine models to make overall assignments of EC number to
      an accuracy of 35% with the top-ranked prediction, rising to 60% accuracy with
      the top two ranks. In doing so we demonstrate the utility of simple structural
      attributes in protein function prediction and shed light on the link between
      structure and function. We apply our methods to predict the function of every
      currently unclassified protein in the Protein Data Bank.

PMID- 15567422
TI  - Phenotypic analysis of dopamine receptor knockout mice; recent insights into the
      functional specificity of dopamine receptor subtypes.
AB  - The functional specificity of dopamine receptor subtypes remains incompletely
      understood, in part due to the absence of highly selective agonists and
      antagonists. Phenotypic analysis of dopamine receptor knockout mice has been
      instrumental in identifying the role of dopamine receptor subtypes in mediating
      dopamine's effects on motor function, cognition, reward, and emotional behaviors.
      In this article, we provide an update of recent studies in dopamine receptor
      knockout mice and discuss the limitations and future promise of this approach.

PMID- 15567423
TI  - The mGlu2/3 receptor agonist LY379268 injected into cortex or thalamus decreases
      neuronal injury in retrosplenial cortex produced by NMDA receptor antagonist MK
      801: possible implications for psychosis.
AB  - The non-competitive NMDA receptor antagonists, including PCP (phencyclidine),
      ketamine, and MK-801 (dizocilpine) produce psychosis in humans and injure neurons
      in retrosplenial cortex in adult rodent brain. This study examined the effects of
      the metabotropic mGlu2/3 agonist LY379268 and antagonist LY341495 on cortical
      injury produced by systemic MK-801 (1 mg/kg i.p.) in adult female rats. Systemic
      injections of mGlu2/3 agonist LY379268, but not mGlu2/3 antagonist LY341495,
      decreased the injury in the retrosplenial cortex produced by systemic MK-801 as
      assessed by Hsp70 induction. Bilateral injections of LY379268, but not vehicle,
      into retrosplenial cortex or bilateral injections of LY379268 into anterior
      thalamus also decreased the injury in retrosplenial cortex produced by systemic
      MK-801. The data show that bilateral activation of mGlu2/3 glutamate receptors in
      cortex or anterior thalamus decreases the neuronal injury in retrosplenial cortex
      produced by systemic MK-801. Because antipsychotic medications decrease cortical
      injury produced by NMDA antagonists in rodents and decrease psychosis in humans,
      mGlu2/3 agonists that decrease cortical injury produced by NMDA antagonists in
      rodents might be evaluated for decreasing psychosis in people.

PMID- 15567424
TI  - Gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB receptor (GABABR)
      binding sites are distinctive from one another: molecular evidence.
AB  - gamma-Hydroxybutyric Acid (GHB) is thought to be a weak partial agonist at the
      gamma-aminobutyric acid(B) Receptor (GABA(B)R), but the precise relationship of
      the GHB receptor (GHBR) to the GABA(B)R remains unclear. In order to test the
      hypothesis that the GHBR is not identical to the GABA(B)R, we conducted two
      groups of experiments. First, GABA(B)R subtype 1 (R1) and/or subtype 2 (R2) were
      over expressed in HEK 293 cells and membrane binding studies on the transfected
      cells done using [(3)H]GHB and [(3)H] (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H
      benzo[a][7]annulen-6-ylidene) ethanoic acid ([(3)H]NCS-382). The latter is a
      specific antagonist at the GHB binding site. Second, [(3)H]GHB and [(3)H]NCS-382
      autoradiographic binding studies were done on the brains of mice in which the
      gene for GABA(B)R1a was deleted. Such mice do not have a functioning GABA(B)R.
      There was no detectable specific [(3)H]GHB or [(3)H]NCS-382 binding in HEK 293
      cells transfected with GABA(B)R1, R2, or R1/R2. Binding to [(3)H]CGP54626A, a
      high affinity GABA(B)R antagonist, was absent in GABA(B)R1a(-/-) mice. There was
      no difference in [(3)H]NCS-382 binding observed in the brains of GABA(B)R1a(-/-),
      GABA(B)R1a(+/-) or GABA(B)R1a(+/+) mice. Specific [(3)H]GHB binding was observed
      in the brain of GABA(B)R1a(-/-) mice but was significantly lower than in wild
      type mice. These data support the hypothesis that the GHB binding site is
      separate and distinct from the GABA(B)R.

PMID- 15567425
TI  - Modulation of morphine-induced Fos-immunoreactivity by the cannabinoid receptor
      antagonist SR 141716.
AB  - A growing body of evidence suggests the existence of a functional interaction
      between opioid and cannabinoid systems. The present study further investigated
      this functional interaction by examining the combined effects of morphine and the
      cannabinoid receptor antagonist SR 141716 on Fos-immunoreactivity (Fos-IR), a
      marker for neural activation. Male albino Wistar rats were treated with SR 141716
      (3 mg/kg, intraperitoneally), morphine HCl (10 mg/kg, subcutaneously), vehicle,
      or SR 141716 and morphine combined (n = 6 per group). Rats were injected with
      morphine or its vehicle 30-min after administration of SR 141716 or its vehicle
      and perfused 3 h later. Locomotor activity and body temperature were both
      increased in the morphine-treated group and SR 141716 significantly inhibited
      these effects. Morphine increased Fos-IR in several brain regions including the
      caudate-putamen (CPu), cortex (cingulate, insular and piriform), nucleus
      accumbens (NAS) shell, lateral septum (LS), bed nucleus of the stria terminalis
      (BNST), median preoptic nucleus (MnPO), medial preoptic nucleus (MPO),
      hypothalamus (paraventricular, dorsomedial and ventromedial), paraventricular
      thalamic nucleus (PV), amygdala (central and basolateral nuclei), dorsolateral
      periaqueductal gray, ventral tegmental area (VTA), and Edinger-Westphal nucleus.
      SR 141716 alone increased Fos-IR in the cortex (cingulate, insular and piriform),
      NAS (shell), LS, BNST, hypothalamus (paraventricular, dorsomedial and
      ventromedial), PV, amygdala (central, basolateral and medial nuclei), VTA, and
      Edinger-Westphal nucleus. SR 141716 attenuated morphine-induced Fos-IR in several
      regions including the CPu, cortex, NAS (shell), LS, MnPO, MPO, paraventricular
      and dorsomedial hypothalamus, PV, basolateral amygdala, VTA, and Edinger-Westphal
      nucleus (EW). These results provide further support for functional interplay
      between the cannabinoid and opioid systems. Possible behavioural and
      physiological implications of the interactive effects of SR 141716 on morphine
      induced Fos-IR are discussed.

PMID- 15567426
TI  - Differential effects of THC- or CBD-rich cannabis extracts on working memory in
      rats.
AB  - Cannabinoid receptors in the brain (CB(1)) take part in modulation of learning,
      and are particularly important for working and short-term memory. Here, we
      employed a delayed-matching-to-place (DMTP) task in the open-field water maze and
      examined the effects of cannabis plant extracts rich in either Delta(9)
      tetrahydrocannabinol (Delta(9)-THC), or rich in cannabidiol (CBD), on spatial
      working and short-term memory formation in rats. Delta(9)-THC-rich extracts
      impaired performance in the memory trial (trial 2) of the DMTP task in a dose
      dependent but delay-independent manner. Deficits appeared at doses of 2 or 5
      mg/kg (i.p.) at both 30 s and 4 h delays and were similar in severity compared
      with synthetic Delta(9)-THC. Despite considerable amounts of Delta(9)-THC
      present, CBD-rich extracts had no effect on spatial working/short-term memory,
      even at doses of up to 50 mg/kg. When given concomitantly, CBD-rich extracts did
      not reverse memory deficits of the additional Delta(9)-THC-rich extract. CBD-rich
      extracts also did not alter Delta(9)-THC-rich extract-induced catalepsy as
      revealed by the bar test. It appears that spatial working/short-term memory is
      not sensitive to CBD-rich extracts and that potentiation and antagonism of
      Delta(9)-THC-induced spatial memory deficits is dependent on the ratio between
      CBD and Delta(9)-THC.

PMID- 15567427
TI  - Effect of estrogen receptor agonists treatment in MPTP mice: evidence of
      neuroprotection by an ER alpha agonist.
AB  - Beneficial effects of 17 beta-estradiol (17 beta-E(2)) on 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced striatal dopamine (DA) depletion are
      well documented but the mechanisms implicated are poorly understood. The present
      experiments investigated the effect of estrogen receptor (ER) agonists treatment
      in MPTP mice as compared to 17 beta-E(2). The agonists specific for each subtype
      were 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT) (ER alpha
      agonist), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and Delta 3-diol (5
      androsten-3 beta, 17 beta-diol, also known as 5-androstenediol, androstenediol or
      hermaphrodiol) (ER beta agonists). Biogenic amines were assayed by HPLC with
      electrochemical detection. 8 mg/kg of MPTP was administered to give a moderate
      depletion of striatal DA and its metabolite dihydroxyphenylacetic acid (DOPAC).
      Protection against MPTP-induced striatal DA and DOPAC depletion was obtained with
      PPT and 17 beta-E(2) but not with DPN or Delta 3-diol. The striatal dopamine
      transporter (DAT) was assayed by autoradiography with [(125)I]RTI-121-specific
      binding. A positive and significant correlation was observed between striatal DA
      concentrations and [(125)I]RTI-121-specific binding, suggesting that estrogenic
      treatment that prevented the MPTP-induced DA depletion also prevented loss of
      DAT. The effect of PPT suggests the implication of an ER alpha in the estrogenic
      neuroprotection against MPTP. Pointing out which ER is implicated in
      neuroprotection becomes helpful in designing more specific estrogenic drugs for
      protection of the aging brain.

PMID- 15567428
TI  - Magnesium-deficient diet alters depression- and anxiety-related behavior in mice-
      influence of desipramine and Hypericum perforatum extract.
AB  - A relation between magnesium (Mg) status and mood disorders has been suggested,
      but evidence remains inconsistent. Therefore, we examined in mice whether Mg
      depletion would alter behavior evaluated in established animal models of
      depression and anxiety and whether these effects would be sensitive to
      antidepressants. Compared to control mice fed with normal diet, mice receiving a
      low Mg diet (10% of daily requirement) for several weeks displayed increased
      immobility time in the forced swim test, indicating enhanced depression-like
      behavior. In addition, the partial Mg-depletion increased anxiety-related
      behavior in the light/dark and open field test, while locomotor activity or motor
      coordination was not influenced. Chronic oral administration of desipramine (30
      mg/kg/day), or Hypericum extract LI160 (Hyp, 380 mg/kg/day) prevented the "pro
      depression-like" forced swim behavior in Mg-depleted mice. Furthermore, the
      increase in anxiety-related behavior of Mg-depleted mice was abolished in both
      the open field and light dark test by Hyp. Taken together, we report that Mg
      depletion leads to enhanced depression- and anxiety-related behavior in mice,
      which was further validated by the reversibility of the behavioral changes by
      known antidepressant and anxiolytic substances. Further, the utility of Mg
      depletion as a new screening model for clinically active antidepressant and
      anxiolytic drugs is suggested.

PMID- 15567429
TI  - Novel neuronal targets for the acetylcholinesterase inhibitor donepezil.
AB  - The effects of the acetylcholinesterase inhibitor donepezil on cell viability and
      proliferation events have been analysed in SH-SY5Y human neuroblastoma cells.
      Short- (48 h) or long-term (7 days) exposure of SH-SY5Y cells to donepezil (100
      nM-10 microM) induced a concentration-dependent inhibition of cell proliferation
      that was not modified by muscarinic and nicotinic receptor antagonists, or
      mimicked by galantamine, and was not related to induction of apoptosis. By
      analysing the distribution profile of cell populations within the cell cycle
      following treatment with 10 microM donepezil, a reduction of cells in the S-G2/M
      phases of the cycle and a parallel increase of the G0/G1 population were
      observed. In addition, the expression of two cyclins of the G1/S and G2/M
      transitions, cyclin E and cyclin B, was significantly reduced in donepezil
      treated cells. In contrast, the expression of the cell cycle inhibitor p21
      rapidly (6 h) increased following exposure to the drug. Finally, donepezil
      increased the expression of the neuronal marker MAP-2 in selected subpopulations
      of SH-SY5Y cells, suggesting that the effect on cell proliferation by donepezil
      may correlate to a trend to neuronal differentiation.

PMID- 15567430
TI  - Anticonvulsant effects of carbenoxolone in genetically epilepsy prone rats
      (GEPRs).
AB  - Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor
      of gap junctional intercellular communication. Systemic administration of CBX was
      able to decrease the seizure severity score and to increase the latency time of
      seizure onset in genetically epilepsy prone rats (GEPRs). In particular,
      intravenous or intraperitoneal administration of carbenoxolone (5-30 mg/kg)
      produced a dose-dependent and significant reduction in the clonic and tonic
      phases of the audiogenic seizures in GEPRs. The anticonvulsant doses were not
      associated with an impairment of motor coordination. The bilateral microinjection
      of CBX (0.001-0.50 microg/0.5 microl) into the inferior colliculi, the substantia
      nigra (pars reticulata or compacta) and the inferior olivary complex was able to
      reduce the seizure severity score in a dose-dependent manner. The anticonvulsant
      effects were longer lasting after focal microinjection than after systemic
      administration. No anticonvulsant effects were observed following focal bilateral
      microinjections of glycyrrhizin into the same brain areas where CBX was shown to
      be effective.

PMID- 15567431
TI  - Independent roles of perforin, granzymes, and Fas in the control of Friend
      retrovirus infection.
AB  - Cytotoxic T-cells (CTL) play a central role in the recovery of mammalian hosts
      from retroviral infections. However, the molecular pathways that mediate the
      antiretroviral activity of CTL are still elusive. Here we explore the protective
      role of the two main cytolytic pathways of CTL, that is, granule exocytosis and
      Fas/Fas ligand (FasL), in acute and persistent Friend retrovirus (FV) infection
      of mice. For this purpose, we have used mutant mouse strains with targeted gene
      defects in one or more components of the two cytolytic pathways including
      perforin, granzyme A, granzyme B, Fas, and FasL. The important function of CTL in
      resistance of C57BL/6 (B6) mice to FV is emphasized by the finding that depletion
      of CD8+ T-cells prior to virus infection resulted in severe splenomegaly and high
      viral loads in blood and spleen tissue. Analysis of primary FV infection in
      knockout mice revealed that acute infection was readily controlled in the absence
      of functional Fas. Most notably in the presence of Fas/FasL each of the three
      effector molecules of the exocytosis pathway (i.e., perforin, granzyme A, and
      granzyme B) was capable on its own to mediate suppression of virus replication
      and protection from leukemia. However, triple knockout mice lacking perforin and
      the two granzymes were fully susceptible to FV-induced leukemia. In contrast to
      acute infection the Fas/FasL pathway was mandatory for effective control of FV
      replication during persistent infection. These findings suggest novel pathways of
      CTL-mediated viral defense and contribute towards a better understanding of the
      molecular mechanisms of CTL activity in retroviral infections.

PMID- 15567432
TI  - Two novel adeno-associated viruses from cynomolgus monkey: pseudotyping
      characterization of capsid protein.
AB  - We demonstrated the presence of two adeno-associated viruses (AAVs), designated
      AAV10 and AAV11, in cynomolgus monkeys by isolating and sequencing the entire
      viral coding regions from the monkey DNA. AAV10 and AAV11 capsid proteins shared
      84% and 65%, respectively, of amino acids with AAV2. A phylogenetic analysis of
      AAV capsid proteins showed that AAV10 and AAV11 resembled most AAV8 and AAV4,
      respectively. To characterize the capsid protein, we pseudotyped an AAV2 vector
      with the monkey AAV capsid proteins and examined the resulting pseudotypes
      AAV2/10 and AAV2/11, in comparison with the AAV2 vector, for their host ranges in
      cell lines and tissue tropism in mice. AAV2/10 and AAV2/11 transduced primate
      cells less efficiently than AAV2. Whereas AAV2 transduced undifferentiated C2C12
      mouse myoblasts more efficiently than differentiated ones, AAV2/10 and AAV2/11
      transduced the undifferentiated myoblasts less efficiently than differentiated
      ones. Three weeks after injection to the muscle of the hind legs, AAV2/10 and
      AAV2 induced transgene expression similarly, but AAV2/11 did not transduce the
      skeletal muscle. Six weeks after systemic administration, transduced vector DNA
      was detected by PCR in the liver and spleen of mice inoculated with AAV2, in the
      liver, heart, muscle, lung, kidney, and uterus of mice with AAV2/10, and the
      muscle, kidney, spleen, lung, heart, and stomach of mice with AAV2/11. Mouse
      antisera against capsid protein VP2 of the three AAVs neutralized the respective
      vector particles in a type-specific manner. The results indicate that AAV10 and
      AAV11 capsid proteins, which are antigenically distinct from each other and AAV2,
      are likely to determine their host ranges and tissue tropism that are different
      from AAV2s, suggesting that cynomolgus AAVs could provide a broader choice of
      pseudotype AAV vectors for gene therapy.

PMID- 15567433
TI  - Respiratory syncytial virus deficient in soluble G protein induced an increased
      proinflammatory response in human lung epithelial cells.
AB  - Respiratory syncytial virus (RSV) is worldwide the single most important
      respiratory pathogen in infancy and early childhood. The G glycoprotein of RSV,
      named attachment protein, is produced by RSV-infected lung epithelial cells in
      both a membrane-anchored (mG protein) and a soluble form (sG protein) that is
      secreted by the epithelial cell. Currently, the biological role of the sG protein
      in primary RSV infection is still elusive. Therefore, we analyzed the
      inflammatory response of human lung epithelial cells (A549) infected either with
      wild-type RSV (RSV-WT) or a spontaneous mutant thereof deficient in the
      production of secreted G protein (RSV-DeltasG). Our data reveal that RSV-DeltasG,
      in comparison to RSV-WT, induced an increased cell surface expression of ICAM-1
      on A549 cells and an enhanced release of the chemokines IL-8 and RANTES after 20
      h postinfection. The increased protein expression pattern correlated with an
      enhanced mRNA level encoding for ICAM-1, IL-8, and RANTES, respectively.
      Furthermore, epithelial cells infected with RSV-DeltasG showed a more increased
      binding activity of the transcription factor NF-kappaB when compared to RSV-WT.
      In contrast, the mutant RSV-DeltasG replicated less efficiently in A549 cells
      than RSV-WT. Our data suggest that RSV, in the course of an ongoing infection,
      reduces by the production of sG protein the detrimental inflammatory response
      evolved by the infected resident lung epithelial cell and thereby supports its
      own replication.

PMID- 15567434
TI  - Activation of c-myb by 5' retrovirus promoter insertion in myeloid neoplasms is
      dependent upon an intact alternative splice donor site (SD') in gag.
AB  - Alternative splicing in Mo-MuLV recruits a splice donor site, SD', within the gag
      that is required for optimal replication in vitro. Remarkably, this SD' site was
      also found to be utilized for production of oncogenic gag-myb fusion RNA in 100%
      of murine-induced myeloid leukemia (MML) in pristane-treated BALB/c mice.
      Therefore, we investigated the influence of silent mutations of SD' in this
      model. Although there was no decrease in the overall incidence of disease, there
      was a decrease in the incidence of myeloid leukemia with a concomitant increase
      in lymphoid leukemia. Importantly, there was a complete lack of myeloid tumors
      associated with 5' insertional mutagenic activation of c-myb, suggesting the
      specific requirement of the SD' site in this mechanism.

PMID- 15567435
TI  - Comparisons of the genetic structure of populations of Turnip mosaic virus in
      West and East Eurasia.
AB  - The genetic structure of populations of Turnip mosaic virus in Eurasia was
      assessed by making host range and gene sequence comparisons of 142 isolates. Most
      isolates collected in West Eurasia infected Brassica plants whereas those from
      East Eurasia infected both Brassica and Raphanus plants. Analyses of
      recombination sites (RSs) in five regions of the genome (one third of the full
      sequence) showed that the protein 1 (P1 gene) had recombined more frequently than
      the other gene regions in both subpopulations, but that the RSs were located in
      different parts of the genomes of the subpopulations. Estimates of nucleotide
      diversity showed that the West Eurasian subpopulation was more diverse than the
      East Eurasian subpopulation, but the Asian-BR group of the genes from the latter
      subpopulation had a greater nonsynonymous/synonymous substitution ratio,
      especially in the P1, viral genome-linked protein (VPg) and nuclear inclusion a
      proteinase (NIa-Pro) genes. These subpopulations seem to have evolved
      independently from the ancestral European population, and their genetic structure
      probably reflects founder effects.

PMID- 15567436
TI  - Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in
      activated PBMC by a mechanism dependent on gp41 function.
AB  - Feline Immunodeficiency Virus (FIV) is a lentivirus that causes immunodeficiency
      in cats, which parallels HIV-1-induced immunodeficiency in humans. It has been
      established that HIV envelope (Env) glycoprotein mediates T cell loss via a
      mechanism that requires CXCR4 binding. The Env glycoprotein of FIV, similar to
      HIV, requires CXCR4 binding for viral entry, as well as inducing membrane fusion
      leading to syncytia formation. However, the role of FIV Env in T cell loss and
      the molecular mechanisms governing this process have not been elucidated. We
      studied the role of Env glycoprotein in FIV-mediated T cell apoptosis in an in
      vitro model. Our studies demonstrate that membrane-expressed FIV Env induces
      apoptosis in activated feline peripheral blood mononuclear cells (PBMC) by a
      mechanism that requires CXCR4 binding, as the process was inhibited by CXCR4
      antagonist AMD3100 in a dose-dependent manner. Interestingly, studies regarding
      the role of CD134, the recently identified primary receptor of FIV, suggest that
      binding to CD134 may not be important for induction of apoptosis in PBMC.
      However, inhibiting Env-mediated fusion post CXCR4 binding by FIV gp41-specific
      fusion inhibitor also inhibited apoptosis. Under similar conditions, a fusion
      defective gp41 mutant was unable to induce apoptosis in activated PBMC. Our
      findings are the first report suggesting the potential of FIV Env to mediate
      apoptosis in bystander cells by a process that is dependent on gp41 function.

PMID- 15567437
TI  - Characterization of nonconventional hepatitis B viruses lacking the core
      promoter.
AB  - The core gene (C-gene) promoter and regulatory sequences play a central role in
      the hepatitis B virus (HBV) life cycle. They are essential for the synthesis of
      the pregenomic and precore mRNA. The pregenomic RNA is the template required for
      replication and also the template for the synthesis of the core protein and
      polymerase. Here, we report the in vivo existence and functional characterization
      of HBV variants that lack the C-gene promoter region and the regulatory sequences
      located therein. HBV promoter fragments were isolated by PCR from sera of chronic
      carriers and characterized. Truncated promoter elements were identified, and then
      tested in the context of wild-type genomes in the HuH-7 cell line. The expression
      of the recombinant HBV genome resulted in the synthesis of surface proteins, and
      low level of core protein as well as a transcript pattern similar to, but smaller
      in size to wild-type virus. The recombinant HBV genome with the truncated
      promoter region produced pregenomic RNA-like transcripts. These transcripts were
      encapsidated and reverse transcribed when complemented by sufficient core and
      polymerase protein. These date provide an explanation as to why such deletion
      mutants of HBV can be produced at all, they highlight the functional potentials
      of viral sequences activated by mutations and may be of relevance for viral
      evolution and persistence.

PMID- 15567438
TI  - A complex of seven vaccinia virus proteins conserved in all chordopoxviruses is
      required for the association of membranes and viroplasm to form immature virions.
AB  - Early events in vaccinia virus (VAC) morphogenesis, particularly the formation of
      viral membranes and their association with viroplasm, are poorly understood.
      Recently, we showed that repression of A30 or G7 expression results in the
      accumulation of normal viral membranes that form empty-looking immature virions
      (IV), which are separated from large masses of electron-dense viroplasm. In
      addition, A30 and G7 physically and functionally interact with each other and
      with the F10 protein kinase. To identify other proteins involved in early
      morphogenesis, proteins from cells that had been infected with vaccinia virus
      expressing an epitope-tagged copy of F10 were purified by immunoaffinity
      chromatography and analyzed by gel electrophoresis. In addition to F10, A30, and
      G7, viral proteins A15, D2, D3, and J1 were identified by mass spectrometry of
      tryptic peptides. Further evidence for the complex was obtained by
      immunopurification of proteins associated with epitope-tagged A15, D2, and D3.
      The previously unstudied A15, like other proteins in the complex, was expressed
      late in infection, associated with virus cores, and required for the stability
      and kinase activity of F10. Biochemical and electron microscopic analyses
      indicated that mutants in which A15 or D2 expression was regulated by the
      Escherichia coli lac operator system exhibited phenotypes characterized by the
      presence of large numbers of empty immature virions, similar to the results
      obtained with inducible A30 and G7 mutants. Empty immature virions were also seen
      by electron microscopy of cells infected with temperature-sensitive mutants of D2
      or D3, though the numbers of membrane forms were reduced perhaps due to
      additional effects of high temperature.

PMID- 15567439
TI  - Identification and characterization of a DNA photolyase-containing baculovirus
      from Chrysodeixis chalcites.
AB  - A hitherto unknown single nucleocapsid nucleopolyhedrovirus (SNPV) with a unique
      property was isolated from larvae of the looper Chrysodeixis chalcites
      (Lepidoptera, Noctuidae, Plusiinae). Polyhedrin, lef-8, and pif-2 gene sequences
      were obtained by PCR with degenerate primers and used for phylogenetic analysis.
      ChchNPV belonged to class II NPVs and its polyhedrin sequence was most similar to
      that of class II NPVs of other members of the subfamily Plusiinae. Further
      genetic characterization involved the random cloning of HindIII fragments into a
      plasmid vector and analysis by end-in sequencing. A gene so far unique to
      baculoviruses was identified, which encodes a putative DNA repair enzyme:
      cyclobutane pyrimidine dimer (CPD) DNA photolyase (dpl). The transcriptional
      activity of this gene was demonstrated in both ChchNPV-infected C. chalcites
      larvae and infected Trichoplusia ni High Five cells by RT-PCR and 5' and 3' RACE
      analysis. The possible role of this gene in the biology of the virus is
      discussed.

PMID- 15567440
TI  - A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev.
AB  - HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells,
      which allows formation of infectious HIV-1 virions. We have identified a putative
      DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev,
      through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev
      as "bait". DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of
      DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)
      containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev-
      cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with
      HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as
      to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE
      axis. Moreover, down-regulation of DDX1 altered the steady state subcellular
      distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These
      findings indicate that DDX1 is a critical cellular co-factor for Rev function,
      which maintains the proper subcellular distribution of this lentiviral regulatory
      protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1
      persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV
      1 strategies and therapeutics.

PMID- 15567441
TI  - The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat
      through a pathway responsible for biological activity.
AB  - Cell surface heparan sulfate proteoglycans (HSPGs) mediate internalization of HIV
      1 Tat. Herein, we report that human WiDr cells, which express perlecan but no
      other HSPGs, can internalize 125I-labeled Tat with minimal lysosomal degradation.
      Pre-treatment of cells with heparitinase almost completely abolished 125I-Tat
      surface binding, while the use of an HIV-1 long terminal repeat (LTR) promoter
      reporter construct demonstrated that transactivation was potently blocked by
      pretreatment of cells with heparitinase, indicating an essential role for
      perlecan in the biologic effects of Tat. We conclude that the perlecan mediates
      Tat uptake and is required for HIV-1 LTR-directed transactivation in this human
      cell type.

PMID- 15567442
TI  - Proteomics of herpes simplex virus infected cell protein 27: association with
      translation initiation factors.
AB  - The herpes simplex virus (HSV) immediate early ICP27 protein plays an essential
      role in stimulating viral early and late gene expression. ICP27 appears to be
      multifunctional in that it has been reported to stimulate viral late gene
      transcription, polyadenylation site usage, and RNA export. We report here on
      proteomic studies involving immunoprecipitation of ICP27 and mass spectrometric
      identification of co-precipitated proteins. These studies show an association of
      ICP27 with the cellular translation initiation factors poly A binding protein
      (PABP), eukaryotic initiation factor 3 (eIF3), and eukaryotic initiation factor
      4G (eIF4G) in infected cells. Immunoprecipitation-western blot studies confirmed
      these associations. Finally, purified MBP-tagged ICP27 (MBP-27) can interact with
      eIF3 subunits p47 and p116 in vitro. These results suggest that ICP27 may also
      play a role in stimulating translation of certain viral and host mRNAs and/or in
      inhibiting host mRNA translation.

PMID- 15567443
TI  - Efficient bunyavirus rescue from cloned cDNA.
AB  - Bunyaviruses are trisegmented, negative-sense RNA viruses. Previously, we
      described a rescue system to recover infectious Bunyamwera virus (genus
      Orthobunyavirus) entirely from cloned cDNA (Bridgen, A. and Elliott, R.M. (1996)
      Proc. Nat. Acad. Sci. USA 93, 15400-15404) utilizing a recombinant vaccinia virus
      expressing bacteriophage T7 RNA polymerase to drive intracellular transcription
      of transfected T7 promoter-containing plasmids. Here we report efforts to improve
      the efficiency of the system by comparing different methods of providing T7
      polymerase. We found that a BHK-derived cell line BSR-T7/5 that constitutively
      expresses T7 RNA polymerase supported efficient and reproducible recovery of
      Bunyamwera virus, routinely generating >10(7) pfu per rescue experiment.
      Furthermore, we show that the virus can be recovered from transfecting cells with
      just three plasmids that express full-length antigenome viral RNAs, greatly
      simplifying the procedure. We suggest that this procedure should be applicable to
      viruses in other genera of the family Bunyaviridae and perhaps also to
      arenaviruses.

PMID- 15567444
TI  - Complete or near-complete nucleotide sequences of hepatitis E virus genome
      recovered from a wild boar, a deer, and four patients who ate the deer.
AB  - Zoonosis has been implicated in hepatitis E virus (HEV) transmission. We examined
      wild boar living in a forest of Hyogo prefecture, Japan, and found HEV RNA in
      three of seven boars. A full-genome HEV isolate from one of them was revealed to
      be 99.7% identical to a previous isolate from a wild deer hunted in the same
      forest and to those from four patients who contracted hepatitis E after eating
      raw meat of the deer. These findings suggest an interspecies HEV transmission
      between boar and deer in their wild life, and that both animals might serve as an
      infection source for human beings as suggested previously.

PMID- 15567446
TI  - Evidence based treatment of the antiphospholipid syndrome II. Optimal
      anticoagulant therapy for thrombosis.
AB  - INTRODUCTION: Current consensus recommendations suggest that patients with
      antiphospholipid antibodies (APLA) are at high risk of recurrent arterial or
      venous thromboembolism (VTE) despite warfarin administered to achieve an
      international normalized ratio (INR) of 2.0 to 3.0. These recommendations have
      been called into question by three recently reported studies. METHODS: We sought
      to determine the current "best practice" for the prevention of recurrent TE in
      patients with APLA and TE. Data was derived from a MEDLINE search and review of
      recent conference abstracts. The literature search was confined to studies of
      treatment to prevent recurrent thrombosis in patients with APLA. RESULTS: The
      overall proportion of patients suffering recurrent TE when allocated to moderated
      intensity warfarin (target INR of 2.0 to 3.0) was 5/113 (4.4%), and it was 11/110
      (10.0%) when such patients were randomized to high-intensity warfarin (target INR
      of 3.0 to 4.0). APLA-positive patients with noncardioembolic/nonatheroembolic
      stroke appear to have similar risks of recurrent TE whether they are treated with
      warfarin or aspirin. DISCUSSION: Patients with APLA and TE have an acceptable
      rate of recurrent TE if they are treated with usual-intensity warfarin. Patients
      with APLA and stroke are probably best treated with aspirin, while those with
      other forms of arterial TE are likely best treated with moderate-intensity
      warfarin plus aspirin.

PMID- 15567447
TI  - A review of the effects of the oral direct thrombin inhibitor ximelagatran on
      coagulation assays.

PMID- 15567448
TI  - Is there a link between CD146, a novel adhesion molecule and other markers of
      endothelial dysfunction in nephrotic syndrome and continuous ambulatory
      peritoneal dialysis?
AB  - BACKGROUND: CD146 is a novel cell adhesion molecule localized at the endothelial
      junction. Its increased plasma levels in chronic renal failure are linked to
      endothelial dysfunction. Endothelial dysfunction and hemostatic disturbances, a
      common feature of nephrotic syndrome (NS), mimics a state of protein loosing by
      peritoneal membrane in patients on chronic ambulatory peritoneal dialyses (CAPD).
      The aim of the study was to assess CD146 in relation to other markers of
      endothelial cell injury in patients with NS in comparison to patients on CAPD.
      MATERIALS AND METHODS: We studied 45 CAPD patients, 43 patients with nephrotic
      syndrome and 25 healthy volunteers. Markers of endothelial cell injury: TFPI
      total, full length, truncated, von Willebrand factor, trombomodulin, P-selectin,
      E-selectin, ICAM, VCAM and CD146 were assessed using commercially available kits.
      RESULTS: All these markers studied except selectins were significantly elevated
      in patients with NS and CAPD when compared to the healthy volunteers. In CAPD,
      VCAM, thrombomodulin and CD146 were significantly elevated over NS patients.
      CD146 correlated significantly with ICAM as well as total and truncated TFPI in
      CAPD patients. Moreover, total TFPI was positively related to VCAM. CD146
      correlated with ICAM in NS, whereas in healthy volunteers CD146 correlated only
      with TFPI concentration. CONCLUSIONS: Our studies indicate that in nephrotic
      patients, as well as in CAPD, there is an evidence of endothelial cell injury.
      Correlations between CD146 and adhesion molecules and TFPI might further support
      its use as a endothelial cell function marker.

PMID- 15567449
TI  - Late saphenous vein graft occlusion in patients with coronary bypass: possible
      role of aspirin resistance.
AB  - BACKGROUND: Late venous graft thrombosis, leading to recurrent ischemia, is
      frequently encountered in old, degenerated vein grafts with advanced
      atherosclerotic plaque formation. Aspirin has been indicated to maintain venous
      graft patency in the post-operative period. However, there is considerable
      evidence that aspirin resistance is of concern in patients with venous grafts.
      MATERIAL AND METHOD: Prospectively enrolled 14 patients (11 male, 3 female, Group
      1), who were shown to have at least one occluded saphenous vein graft on their
      late control coronary angiogram after bypass operation, were compared for the
      presence of aspirin resistance by PFA-100 with age- and sex-matched 14 patients
      (10 male, 4 female, Group 2), who were found patent and well-functioning vein
      grafts without wall irregularities on late post-operative coronary angiograms
      (mean 6.5+/-2.5 years), enrolled as a control group. RESULTS: Mean CT of
      collagen/epinephrine cartridge in Group 1 was 197+/-85 s and significantly less
      than in Group 2 (279+/-44 s; p=0.011). It was found that 50% of patients in Group
      1 were so-called aspirin resistant, whereas in Group 2, this ratio was 7.1%
      (p=0.033). BMI (p=0.038, Beta=-0.322), uric acid level (p=0.023, Beta=-0.355),
      and CT by collagen/epinephrine cartridge (p=0.008, Beta=0.431) were independently
      predicting late occlusion of saphenous vein graft. CONCLUSION: Aspirin resistance
      is highly prevalent in patients with occluded venous grafts at a relatively late
      period.

PMID- 15567450
TI  - Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a
      randomized controlled clinical trial.
AB  - BACKGROUND: Cardiovascular mortality is especially low in southwest France (the
      French Paradox). In previous experimental studies, we found that alcohol-free
      extracts of armagnac could inhibit human platelet function in vitro and
      experimental thrombosis in vivo. To test the possible relevance of these
      findings, we tested the effects of daily use of small quantities of armagnac
      against same alcohol strength, polyphenol-free vodka in healthy volunteers.
      METHOD: Randomized controlled trial comparing 5-year old armagnac (30 ml/day for
      2 weeks) to same alcoholic strength vodka, in 20 healthy volunteers, on platelet
      aggregation induced by ADP, collagen, and thrombin, as well as bleeding time,
      partial thromboplastin time (pTT), and plasma lipids during and after
      consumption. Platelet testing was done blind. RESULTS: After 14 days, ADP-induced
      platelet aggregation was inhibited more in armagnac (-31+/-3.2% compared to
      pretreatment values, p<.01) than in vodka (-11.0+/-6.8%, NS) users (p<.05,
      armagnac vs. vodka). A rebound increase of aggregation was found 2 weeks later in
      vodka but not in armagnac users. The same pattern was found for thrombin-induced
      aggregation, including post-treatment rebound. No effect was found on collagen
      induced aggregation, bleeding time, pTT, or plasma lipids. CONCLUSION: The
      chronic ingestion of moderate quantities of armagnac modified platelet
      aggregation to ADP in healthy volunteers. The difference with the effects of same
      alcohol degree vodka is in favour of an effect of the nonalcoholic fraction in
      the effects of armagnac, rather than just alcohol. All spirits may not be equal
      for cardioprotection.

PMID- 15567451
TI  - Heparin-mediated extracorporeal LDL precipitation treating a peripheral arterial
      disease patient suffering from repeated postoperative bypass occlusion.
AB  - Acute occlusion of a peripheral artery is a serious complication in peripheral
      arterial disease (PAD). Traditionally open surgical intervention in combination
      with antithrombotic therapy is the choice for treatment but the beneficial
      effects of both strategies are limited often by the patient's situation and
      therapeutic side effects. Heparin-mediated extracorporeal low-density lipoprotein
      precipitation (H.E.L.P.) apheresis efficiently removes circulating atherogenic
      lipoproteins, fibrinogen and C-reactive proteins as well as various
      proinflammatory and procoagulatory factors. We first report H.E.L.P. apheresis
      treating a PAD patient suffering from repeated postoperative femoropopliteal
      bypass graft occlusion, first, intensively, followed by weekly intervals. Limb
      amputation was avoided and the patient is doing well now. Angiography revealed
      bypass graft remained patent half a year after operation. This case report might
      help to design the regime for preventing postoperative bypass occlusion in
      patients with hyperlipidemia or hyperfibrinogenemia.

PMID- 15567452
TI  - Pharmacokinetics of UH and LMWH are similar with respect to antithrombin
      activity.
AB  - BACKGROUND: The ability to administer low molecular weight heparins (LMWH)
      subcutaneously without laboratory monitoring contributes to their popularity for
      the treatment of thrombotic disorders. Subcutaneous unfractionated heparin,
      although less expensive, is deemed to require routine laboratory monitoring on
      the basis of more variability in drug effect compared to LMWH. However, the more
      predictable pharmacokinetic profiles of low molecular weight heparins are largely
      based on anti-Xa activity, while antithrombin activity may be at least as
      important to their mechanisms of action. METHODS: We performed a clinical
      pharmacokinetic trial to compare the variability in peak antithrombin effect
      between subcutaneous unfractionated heparin and various LMWHs, all given in
      recommended weight-adjusted treatment doses. Sixty-one patients enrolled in a
      warfarin clinic were randomized to receive one of four different weight-adjusted
      subcutaneous heparin doses: unfractionated heparin, 250 units/kg (n=15);
      tinzaparin, 175 units/kg (n=15); dalteparin, 200 units/kg (n=15); or enoxaparin,
      1 mg/kg (n=16). The areas under the curves of antithrombin levels during the
      first 3 h after administration were determined for each patient, and the
      coefficients of variation (CV) and 95% confidence intervals of the AUCs were
      compared among the treatment groups. RESULTS: There was no statistically
      significant difference in the coefficients of variation of antithrombin effect
      between unfractionated heparin (52.8, 95% CI: 32.6-72.9) and enoxaparin (56.5,
      95% CI: 35.7-77.4) or dalteparin (43.5, 95% CI 25.4-61.6). Tinzaparin had
      statistically significant decrease in coefficients of variation (21.6, 95% CI:
      12.2-30.9) relative to unfractionated heparin, dalteparin and enoxaparin.
      CONCLUSIONS: LMWHs, as a class of drugs, are no more predictable in antithrombin
      effect after subcutaneous injection than unfractionated heparin. There were
      considerable differences among LMWHs in the observed variability of antithrombin
      effects, with tinzaparin being somewhat more predictable than the other drugs
      tested.

PMID- 15567453
TI  - Elevated plasma levels of fibrin degradation products by granulocyte-derived
      elastase in patients with deep vein thrombosis.
AB  - Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer and soluble
      fibrin (SF) were examined in 53 patients with deep vein thrombosis (DVT) and in
      100 healthy volunteers. The mean plasma level of D-dimer was 0.92+/-0.81
      microg/ml (+/-S.D.) in healthy volunteers and the mean+2 S.D. value (cutoff value
      for DVT) was 2.53 microg/ml, which was higher than that used in Europe and North
      America. Plasma levels of GE-XDP, D-dimer and SF were significantly higher in
      patients with DVT than in healthy volunteers, and diminished after 1 week of
      treatment with heparin, urokinase or tissue type plasminogen activator, though
      were still higher than those of the control subjects. The sensitivity of GE-XDP,
      D-dimer and SF for DVT was 81.1%, 75.5% and 79.2%, respectively. GE-XDP levels
      correlated with those of D-dimer and SF. Our results indicate that GE-XDP is a
      potentially useful marker for the diagnosis of DVT, suggesting that granulocytes
      are activated in patients with DVT. In our system, the cutoff value of D-dimer
      for the diagnosis of DVT is higher than in western countries, probably due to the
      use of different analytical assays.

PMID- 15567454
TI  - Symptomatic venous thromboembolism in acute leukemia. Incidence, risk factors,
      and impact on prognosis.
AB  - The association between malignant disorders and occurrence of venous
      thromboembolism is well established. Patients with cancer and venous
      thromboembolism have adverse prognosis. No systematic study on the incidence and
      prognostic impact of venous thromboembolism in acute leukemia has been performed
      as yet. We retrospectively evaluated the incidence of symptomatic venous
      thromboembolism before chemotherapy in 719 patients (371 males and 348 females,
      median age of 57.4 years), diagnosed with acute leukemia [534 with acute
      myelogenous leukemia, 185 with acute lymphoblastic leukemia]. Furthermore, the
      relationship of venous thromboembolism to clinical and laboratory parameters and
      its impact on prognosis was assessed. Fifteen patients (2.09%) had venous
      thromboembolism (objectively confirmed in 13 patients) in close temporal
      relationship to the onset of acute leukemia. The incidence of venous
      thromboembolism was the same in acute myelogenous and lymphoblastic leukemia. In
      five patients, pulmonary embolism was documented. Venous thromboembolism occurred
      in all subtypes of acute leukemia, but was most common in promyelocytic leukemia.
      All but one patient were treated with anticoagulants. No patient died from
      treatment-related bleedings or venous thromboembolism. Overall, survival, disease
      free survival, and remission duration did not differ between the patient groups
      with and without venous thromboembolism. In contrast to solid tumors, venous
      thromboembolism before or at diagnosis of acute leukemia is not associated with
      poor prognosis.

PMID- 15567455
TI  - Acute coronary syndromes do not promote prolonged in vivo FXII-dependent
      prothrombotic activity.
AB  - BACKGROUND: Coagulation FXII is activated on contact with lipoprotein particles.
      It has been suggested that contact with subendothelial tissue provides an
      alternative biological surface for FXII activation. Our aim was to investigate
      whether activated FXII (FXIIa) is elevated in patients with coronary
      atherosclerosis, and whether disease status (acute phase or stable state) affects
      circulating levels of FXIIa. METHODS: Circulating FXIIa levels were measured in
      the peripheral blood of 122 patients with coronary atherosclerosis (32, stable
      angina; 54, unstable angina; 36, nQ myocardial infarction) and in 45 age-matched
      subjects (Contr). RESULTS: FXIIa levels (median, first and third quartiles;
      ng/ml) were higher in patients than in Contr: 1.61 (1.26-2.02) vs. 1.34 (1.13
      1.81) (p<0.01). FXIIa levels were similar among patients with stable angina [1.66
      (1.23-1.91)], unstable angina [1.53 (1.21-2.04)], and nQ myocardial infarction
      [1.75 (1.34-2.03)]. The three groups of patients had similar prevalence for most
      atherothrombotic risk factors; patients with stable angina had an increased
      severity of coronary disease, which did not explain the different levels of
      FXIIa. Fasting levels of triglycerides were the best predictor of FXIIa levels in
      our patients. CONCLUSIONS: The finding of similar FXIIa levels among patients in
      either acute or chronic phases of coronary atherosclerosis suggests that the
      initial arterial denudation and the acute-phase response associated to acute
      coronary syndromes are not major determinants for prolonged FXII activation.

PMID- 15567456
TI  - Plasma thrombosis markers following cerebral infarction in African Americans.

PMID- 15567457
TI  - In vivo platelet redistribution and acute transient thrombocytopenia after
      eptifibatide injection in baboons.
AB  - BACKGROUND: The occurrence of thrombocytopenia has been reported during clinical
      eptifibatide (Integrilin) therapy, but the exact mechanism is not yet established
      to explain the varied duration and severity of thrombocytopenia associated with
      glycoprotein (GP) IIb/IIIa inhibitors. We assessed the redistribution of
      platelets in juvenile baboons during acute transient thrombocytopenia that was
      observed after eptifibatide injection. METHODS: Eptifibatide was administered
      intravenously to eight baboons by infusion at 20 microg/kg/min or a bolus
      injection of 10 mg. Platelet distribution was measured with a gamma scintillation
      camera using 111In-labeled autologous platelets. Platelet function and GP
      IIb/IIIa receptor inhibition were evaluated using the Plateletworks system. The
      effects of pretreatment with abciximab (0.4 mg/kg) or human immunoglobulin
      concentrate (0.75 g/kg) were also investigated. RESULTS: Eptifibatide,
      administered as an infusion or a bolus, caused transient thrombocytopenia with
      uptake of platelets predominantly by the liver. The recovery of platelet
      aggregation was associated with the re-entry of platelets from the liver into the
      systemic circulation. Pretreatment with either abciximab (0.4 mg/kg) or human
      intravenous immunoglobulin (IVIG, 0.75 g/kg) attenuated eptifibatide-induced
      thrombocytopenia and the hepatic uptake of radiolabeled platelets. CONCLUSION:
      Acute thrombocytopenia after eptifibatide injection was caused by the transient
      redistribution of platelets to the liver. Attenuation of the decrease in platelet
      count and hepatic sequestration by abciximab and IVIG suggests that
      thrombocytopenia may have been caused by ligand-induced binding site antigen
      induction and recognition by the reticuloendothelial system.

PMID- 15567458
TI  - The difference between clopidogrel responsiveness and posttreatment platelet
      reactivity.
AB  - BACKGROUND: Aggregation is the most common measure of platelet reactivity. The
      relative inhibition of platelet aggregation between pretreatment and
      posttreatment is the most common estimate of clopidogrel responsiveness. However,
      patients responsive to clopidogrel may remain with highly reactive platelets and
      thus have increased thrombotic risk. METHODS: Platelet reactivity was determined
      by ADP-induced aggregation (%) in 62 patients undergoing elective coronary
      stenting at pretreatment and 5 days postprocedure. All patients were on aspirin
      (325 mg) and received 300 mg of clopidogrel immediately poststenting and 75 mg
      qd. Pretreatment reactivity was divided into tertiles. Based on clopidogrel drug
      responsiveness, nonresponders were defined as <10% relative inhibition of
      pretreatment aggregation, semiresponders as 10-30%, and responders as >30%. We
      determined the relation between clopidogrel responsiveness and platelet
      reactivity. RESULTS: Pretreatment reactivity tertiles by 5 microM ADP were: low
      (47+/-9%), moderate (64+/-4%), and high (78+/-6%). Eight patients were
      nonresponders, 18 were semiresponders, and 36 were responders. Clopidogrel
      responsiveness directly correlated with pretreatment reactivity, 86% of
      responders had moderate or high pretreatment reactivity, whereas 75% of
      nonresponders had low pretreatment reactivity. Despite being more responsive, 16%
      of patients with high pretreatment reactivity and 17% with moderate pretreatment
      reactivity remained with moderate posttreatment reactivity. CONCLUSION: Measuring
      clopidogrel responsiveness may overestimate the risk of stent thrombosis in
      nonresponders with low pretreatment reactivity and underestimate risk in those
      responders who remain with high posttreatment platelet reactivity. Posttreatment
      platelet reactivity is a better measure of thrombotic risk than responsiveness to
      clopidogrel.

PMID- 15567459
TI  - An optimized murine model of ferric chloride-induced arterial thrombosis for
      thrombosis research.
AB  - INTRODUCTION/OBJECTIVES: Animal models are important tools in thrombosis research
      and preclinical drug development. Ferric chloride has been widely used to induce
      arterial thrombosis in a variety of species. However, almost all previous reports
      applied a very high concentration of ferric chloride (10-60%) to induce thrombus
      formation leading to difficulties in evaluating the efficacy of antithrombotic
      agents. Thus, the purpose of this study was to refine the ferric-chloride-induced
      thrombosis model to be better suited for thrombosis research. METHODS AND
      RESULTS: Dose-dependent study was used to identify a threshold concentration of
      ferric chloride sufficient for consistent occlusion (as reflected by the Doppler
      blood flow) of the carotid artery in C57BL/6 mice. Ferric chloride concentration
      at or about a threshold of 2.5% was found to be sensitive to anticoagulant (e.g.,
      heparin) and antiplatelet (e.g., clopidogrel) agents. In contrast, the vessel
      rapidly occluded at or above 5% ferric chloride concentration despite
      pretreatment with the antithrombotic agents, even at doses that exerted maximal
      prolongation of tail bleeding time. CONCLUSIONS: Our study provides a simple,
      sensitive and highly controlled method for limiting vessel injury in mice to
      better detect the efficacy of antithrombotic drugs and/or evaluate therapeutic
      targets.

PMID- 15567460
TI  - Identification of low responders to a 300-mg clopidogrel loading dose in patients
      undergoing coronary stenting.
AB  - BACKGROUND: Although patients undergoing coronary stenting routinely receive dual
      antiplatelet treatment to reduce the risk of stent thrombosis, this undesired
      event still occurs. A suboptimal response to clopidogrel treatment (low
      responders) has been suggested to contribute to stent thrombosis. In the present
      study, platelet function profiles were assessed in patients undergoing coronary
      stenting receiving a standard 300-mg clopidogrel loading dose with the aim to
      identify low clopidogrel responders. MATERIALS AND METHODS: Platelet aggregation
      was assessed by light transmittance aggregometry following 6 microM ADP stimuli
      in 48 patients before and 10 min, 4 and 24 h after receiving clopidogrel front
      loading. Patients having > or =40% inhibition of platelet aggregation 24 h after
      clopidogrel administration were defined as normal responders, whereas those
      having <40% inhibition were low responders. Glycoprotein (GP) IIb/IIIa activation
      and P-selectin expression were assessed by whole blood flow cytometry following 2
      microM ADP stimuli at the same time points. Platelet function profiles were
      compared between normal and low clopidogrel responders. RESULTS: Twenty-seven
      patients (56%) were normal responders and 21 (44%) low responders. Baseline GP
      IIb/IIIa activation was higher in low responders (74.6+/-16.6% vs. 58.2+/-24.5%,
      p=0.03). Although GP IIb/IIIa activation reduced following clopidogrel front
      loading in both groups, it remained increased among low responders at 24 h
      (58.6+/-21.3% vs. 40.2+/-28.7%, p=0.05) and during the overall study time course
      (p=0.02). There were no differences in P-selectin expression. CONCLUSIONS: A
      considerable proportion of patients have an early suboptimal response to a 300-mg
      clopidogrel loading dose. An increased GP IIb/IIIa activation before intervention
      may identify this group of patients suggesting the use of a more aggressive
      antithrombotic treatment in these individuals.

PMID- 15567461
TI  - Annexin II cell surface and mRNA expression in human acute myeloid leukaemia cell
      lines.
AB  - INTRODUCTION: Acute promyelocytic leukaemia (APL) (M3) is associated with both a
      characteristic t(15;17) and severe bleeding diathesis caused by disseminated
      intravascular coagulation (DIC) and/or hyperfibrinolysis. It has been suggested
      that annexin II, a coreceptor for tissue plasminogen activator (t-PA) and
      plasminogen (PLG), is overexpressed on the surface of promyelocytes, leading to
      an increased fibrinolytic potential. MATERIALS AND METHODS: This study examined
      the level of annexin II cell surface and mRNA expression in a range of acute
      myeloid leukaemia (AML) cell lines. The evidence that annexin II levels are
      higher in APL would lend support to the hypothesis that the bleeding disorder
      seen in APL is caused by hyperfibrinolysis. RESULTS: Cell surface annexin II was
      found to be expressed at higher levels on NB4 (promyelocytic) cells than on
      either KG1a (early myeloid) or HL60 (myelocytic) cells. However, even higher
      levels were found on U937 and MM6 (histo-monocytic) and HEL (erythroid) cells
      (p<0.01). MM6 cells showed a threefold increase in annexin II mRNA compared to
      any of the other cell lines. CONCLUSIONS: These findings do not fully support the
      concept of the coagulopathy associated with APL being caused by hyperfibrinolysis
      alone. Further investigations are required to identify the significance of
      annexin II expression and regulation in leukaemia.

PMID- 15567462
TI  - Anti-thrombotic effect of proanthocyanidin, a purified ingredient of grape seed.
AB  - INTRODUCTION: Moderate and regular consumption of wine reduces the risk of acute
      coronary thrombotic events. The mechanism of the anti-thrombotic effect of wine
      is not clear. Extract or purified ingredients of grapes have not yet been studied
      for anti-thrombotic effect. MATERIALS AND METHODS: Anti-thrombotic effect of
      proanthocyanidin, a highly purified ingredient of grape seed, was assessed by a
      shear-induced thrombosis test in vitro and by a laser-induced thrombosis test in
      the mouse carotid artery, in vivo. RESULTS AND CONCLUSIONS: Intravenously (20
      mg/kg body weight, BW) or orally (2 x 200 mg/kg BW) administered proanthocyanidin
      significantly inhibited the laser-irradiation induced thrombus formation in the
      carotid artery (both P=0.01). Subsequent to oral administration of
      proanthocyanidin, in vitro platelet reactivity to shear stress has been
      inhibited. The latter suggests that the in vivo anti-thrombotic effect of
      proanthocyanidin may be due to a direct inhibitory effect on platelets.

PMID- 15567463
TI  - Assembly and regulation of prothrombinase complex on B16F10 melanoma cells.
AB  - A number of studies indicate that coagulation proteases play significant roles in
      cancer biology. Melanoma is a highly metastatic cancer, and there is evidence
      that thrombin contributes to this aggressive pattern. However, few studies
      correlate this type of cancer with formation of the prothrombinase complex, which
      is responsible for conversion of prothrombin into thrombin in the coagulation
      system. The aim of this study was to investigate the assembly and regulation of
      prothrombinase complex on the murine melanoma cell line, B16F10. B16F10 cells
      were unable to activate prothrombin except when previously incubated with factor
      Xa. This effect was dependent on factor Xa binding to cell membranes, since no
      activation was detected with Gla-domainless factor Xa. The thrombin formation by
      B16F10-bound factor Xa was enhanced approximately 10 fold in the presence of
      factor Va, indicating the assembly of prothrombinase complex. Differently from
      platelets, B16F10-assembled prothrombinase complex was inhibited by prothrombin
      fragment 1 but not by fragment 2. In addition, bothrojaracin, a specific ligand
      of proexosite I on prothrombin, caused a significant decrease in the zymogen
      activation. Our data demonstrate that B16F10 melanoma cells generate thrombin by
      promoting assembly of the prothrombinase complex. This ability might be
      correlated with the increased metastatic potential of this cell line. Moreover,
      B16F10-assembled prothrombinase complex seems to be modulated in a different way
      from that found for the physiological complex assembled on platelets.

PMID- 15567464
TI  - Agreement of a new whole-blood PT/INR test using capillary samples with plasma
      INR determinations.
AB  - PURPOSE: The objective of the study was to compare in anticoagulated patients the
      international normalized ratio (INR) measured with a new capillary whole-blood
      device, the i-STAT Portable Clinical Analyser, with conventional plasma INR
      obtained from the central laboratory. PATIENTS AND METHODS: Between-cartridge
      variability was first determined with two lyophilized controls with INR levels of
      1.60 and 2.75 (n=10). Next, in 35 patients under different intensities of oral
      anticoagulation, capillary blood INR was measured with two i-STAT devices and was
      compared to central laboratory plasma INR (Innovin reagent and BCS analyser).
      RESULTS: Between-cartridge coefficients of variation were 5% (95%, CI 3.4-9.1)
      and 3% (95%, CI 2.1-5.5) at INR levels of 1.60 and 2.75. Mean INR difference
      between the two i-STAT devices was 0.1, and the correlation coefficient was 0.98.
      Between i-STAT and central laboratory INR, the correlation coefficient was 0.95.
      Bias values were 0.04, 0.2, and -0.04 at INR levels of 2.0, 2.5, and 3.5,
      respectively. CONCLUSION: The INR measured with the i-STAT Portable Clinical
      Analyser is precise and compares well with plasma INR performed in a central
      laboratory.

PMID- 15567465
TI  - Anticoagulant action of melagatran, the active form of the oral direct thrombin
      inhibitor ximelagatran, in umbilical cord and adult plasma: an in vitro
      examination.
AB  - INTRODUCTION: This study was performed to compare the anticoagulant activity of
      melagatran, the active form of the oral direct thrombin inhibitor ximelagatran,
      in umbilical cord plasma with that in adult plasma. In contrast with the most
      frequently administered anticoagulants, the heparins, melagatran acts
      independently of antithrombin (AT). As a consequence, administration of
      melagatran is of special interest in neonates, who have physiologically low
      levels of AT. MATERIALS AND METHODS: Plasma samples were activated under high (as
      used in standard clotting assays) and low (more comparable with the physiological
      milieu) coagulant challenge. In the absence of melagatran, adult plasma clotted
      significantly faster than umbilical cord plasma under high coagulant challenge.
      Conversely, under low coagulant challenge, clotting of adult plasma was
      significantly delayed compared with umbilical cord plasma. For both high and low
      coagulant challenges, clotting times increased and prothrombin fragment 1.2 and
      thrombin-antithrombin (TAT) formation decreased with melagatran in a
      concentration-dependent fashion in umbilical cord and adult plasma. With
      increasing melagatran concentrations, the quotient between prothrombin fragment
      1.2 and TAT formation increased in adult and umbilical cord plasma under both
      high and low coagulant challenges. RESULTS AND CONCLUSIONS: Our in vitro results
      cannot be directly extrapolated to clinical efficacy, but assessing the degree of
      inhibition of thrombin generation may be a useful surrogate for selecting
      effective doses of ximelagatran for in vivo studies in neonates with
      thromboembolic complications.

PMID- 15567466
TI  - Direct-acting fibrinolytic enzymes in shark cartilage extract: potential
      therapeutic role in vascular disorders.
AB  - Fibrinogen and fibrin are molecules with overlapping roles in blood clotting,
      fibrinolysis, wound healing, inflammation, matrix and cellular interactions and
      neoplasia. There is currently much interest in the possible use of fibrinolytic
      agents in human therapeutics. In this study, we report the presence of
      fibrinolytic activities in shark cartilage extract (SCE). In vitro, SCE at 100
      microg/ml completely degraded fibrin gel in an aprotinin-insensitive manner,
      suggesting a non-plasmin molecular nature. SCE was able to cleave all chains of
      fibrinogen and fibrin and the cleavage was completely inhibited by 1,10
      phenanthroline, suggesting an essential role for metalloprotease(s) in this
      process. Using fibrinogen zymography, we show that SCE contains two plasmin
      independent fibrinolytic activities and that these activities are correlated with
      the presence of 58 and 62 kDa proteases in the extract. SCE-fibrinolytic
      activities are inhibited by dithiothreitol, suggesting that disulfide bonds are
      necessary for the protease structure. Finally, using thromboelastography, SCE
      markedly induced retraction of human platelet-rich plasma (PRP) clot, this
      process being completely abolished by 1,10-phenanthroline. These data suggest the
      presence of novel non-plasmin fibrinolytic activities within SCE. This extract
      may thus represent a potential source of new therapeutic molecules to prevent and
      treat vaso-occlusive and thromboembolic disorders.

PMID- 15567467
TI  - A prothrombotic phenotype in the Copenhagen rat strain.
AB  - INTRODUCTION: Experimental and epidemiologic studies have identified several
      potential genetic components for increased thrombotic risk. Studies of thrombosis
      often use rat models without considering the effect of strain differences on
      thrombotic propensity. MATERIALS AND METHODS: A comparison of in vivo thrombotic
      occlusion after small-vessel anastomosis was made between age/weight-matched male
      Copenhagen and Lewis rats. RESULTS: One-day thrombotic occlusion rates were
      significantly higher in Copenhagen arteries (67%) and veins (100%) compared to
      Lewis arteries (8%) and veins (50%), respectively. Single-bolus intravenous
      heparin (150 units/kg body weight) had a slight effect on reducing occlusion
      rates in Copenhagen rats (50% and 67% for arteries and veins, respectively),
      while occlusion was totally prevented by heparin in both vessel types of Lewis
      rats (0% occlusion). In vitro assays for platelet aggregation and coagulation
      revealed no apparent differences between these two rats strains, although AT-III
      levels were slightly higher in Copenhagen rats, contrary to the prothrombotic
      state. CONCLUSIONS: These findings indicate a profound prothrombotic tendency in
      the Copenhagen rat strain and support a broader investigation of the genetic
      basis of this thrombotic potential.

PMID- 15567468
TI  - Elevated FVIII and FIX level in a Behcet's disease patient with intracardiac
      thrombosis and pulmonary arterial aneurysms.

PMID- 15567469
TI  - Galanin and galanin receptors in epilepsy.
AB  - The shift in the balance between the inhibition and the excitation in favor of
      the latter is a major mechanism of the evolvement of epileptic seizures. On the
      neurotransmitter level two major players contribute to such misbalance: an
      inhibitory transmitter gamma-aminobutyric acid, and an excitatory amino acid
      glutamate. Neuropeptides are powerful modulators of classical neurotransmitters,
      and thus represent an intriguing tool for restoring the balance between the
      inhibition and the excitation, through either blocking or activating peptide
      receptors depending on whether a peptide is pro- or anticonvulsant. Galanin, a 29
      amino acid residues neuropeptide which inhibits glutamate release in the
      hippocampus, is a likely member of the anticonvulsant peptide family. During the
      past decade growing evidence has been suggesting that galanin is in fact a
      powerful inhibitor of seizure activity. This review summarizes the state of
      research of galanin in epilepsy, beginning with the first simple experiments
      which showed that central injection of galanin agonists inhibited seizures, and
      that seizures themselves affected galanin signaling in the hippocampus; exploring
      the impact of active manipulation with the expression of galanin and galanin
      receptors on seizures, using transgenic animals, antisense and peptide-expressing
      vector approaches; and concluding with the recent advances in pharmacology, which
      led to the synthesis of non-peptide galanin receptor agonists with anticonvulsant
      properties. We also address recently established functions of galanin in seizure
      associated neuronal degeneration and neuronal plasticity.

PMID- 15567470
TI  - Neuropeptide Y immunoreactivity and corticotropin-releasing hormone mRNA level
      are increased in the hypothalamus of mouse bearing a human oral squamous cell
      carcinoma.
AB  - We examined gene expression of corticotropin-releasing hormone and neuropeptide Y
      level in the hypothalamic paraventricular nucleus of mouse bearing a human oral
      squamous cell carcinoma. A cell line derived from a human oral squamous cell
      carcinoma was inoculated into the lower dorsal area of nude mice. Body weight,
      tumor size and daily food intake were recorded every morning. Mice were
      sacrificed for corticotropin-releasing hormone mRNA in situ hybridization and
      neuropeptide Y immunohistochemistry, when the tumor ratio reached to 11-13% of
      real body weight. The results were compared with the age-matching non-tumor
      controls injected with saline instead of carcinoma cell. Body weight gain was
      significantly reduced in tumor bearing mice, however, no compensatory hyperphagia
      was found, i.e. daily food intake of the tumor mice did not differ from the non
      tumor mice. Both neuropeptide Y immunoreactivity and corticotropin-releasing
      hormone mRNA level were significantly increased in the hypothalamic
      paraventricular nucleus of tumor mice. These results suggest that a human oral
      squamous cell carcinoma may induce anorexia, at least partly, via increasing the
      hypothalamic expression of corticotropin-releasing hormone in the tumor subjects.
      Additionally, neuropeptide Y-induced feeding appears to be inhibited in this
      tumor anorexia model, and this may correlate with increased expression of
      corticotropin-releasing hormone.

PMID- 15567471
TI  - Chlorine inhalation produces nasal airflow limitation in allergic rhinitic
      subjects without evidence of neuropeptide release.
AB  - BACKGROUND: Seasonal allergic rhinitic (SAR) subjects are more physiologically
      reactive to airborne irritants than non-rhinitic (NR) subjects; however the
      mechanism underlying this difference is unclear. OBJECTIVE: We sought to
      determine whether irritant-induced nasal airflow limitation involves neuropeptide
      release into nasal lining fluid, and if so, whether such release occurs
      differentially by rhinitic status. METHODS: Eight SAR and 8 NR subjects were
      exposed to 1.0 ppm chlorine and filtered air in random order during separate
      visits; exposures were via nasal mask and lasted 15 min. Rhinomanometry was
      performed before, immediately post-, and 15 min post-exposure. Following a
      minimum of 2 weeks' time, exposures and symptom reporting were repeated with
      nasal lavage pre- and post-exposure. Neuropeptides (substance P, cacitonin gene
      related protein, vasoactive intestinal peptide, and neuropeptide Y) as well as
      markers of plasma leakage (albumin and urea) and glandular secretion (lysozyme
      and 7F10-mucin) were measured using standard methods. RESULTS: Cl(2) provocation
      significantly increased nasal airway resistance in SAR but not NR subjects
      (p<0.05). Neuropeptide levels in nasal lavage fluid, on the other hand, were
      unaffected, with the exception of a paradoxical increase in vasoactive intestinal
      peptide in non-rhinitic controls post-Cl(2) provocation. CONCLUSIONS: Irritant
      induced nasal airflow limitation is more pronounced among SAR than NR subjects.
      We could not, however, demonstrate a role for neuropeptide release in the nasal
      congestive response of SAR subjects.

PMID- 15567472
TI  - Innate differences in neuropeptide Y (NPY) mRNA expression in discrete brain
      regions between alcohol-preferring (P) and -nonpreferring (NP) rats: a
      significantly low level of NPY mRNA in dentate gyrus of the hippocampus and
      absence of NPY mRNA in the medial habenular nucleus of P rats.
AB  - The neuropeptide Y (NPY) gene in rat chromosome 4 has been shown to play an
      important role in alcohol-seeking behavior. NPY knockout mice drink more alcohol
      than wild-type mice, implicating a link between NPY deficiency and high alcohol
      intake. This is supported by recent studies showing that intracerebroventricular
      injections of NPY reduce alcohol intake in both alcohol-preferring (P) and high
      alcohol-drinking rats. However, it is unknown which anatomical NPY systems are
      involved in alcohol preference. This study was designed to investigate whether
      there are innate differences in NPY mRNA in cerebral cortical areas, dentate
      gyrus (DG) of the hippocampus and medial habenular nucleus (MHb) between P and
      alcohol-nonpreferring (NP) rats, as these discrete brain regions are rich in NPY
      mRNA. [(33)P]-labeled 28-mer oligodeoxynucleotide probe was applied for the in
      situ hybridization study to detect the NPY mRNA, measured using quantitative
      autoradiography. This study revealed an absence of NPY mRNA in the MHb of P rats.
      We found that NPY mRNA was significantly lower in the DG of P rats than NP rats.
      This innate difference of NPY mRNA expression in the DG between P and NP rats is
      region specific. For example, in most of the cerebral cortical areas examined, an
      innate difference was not seen. Our study suggests that lower NPY gene expression
      in the DG and MHb of P rats may be factors contributing to some of the phenotypic
      differences observed between the P and NP lines of rats.

PMID- 15567473
TI  - Forty years in capsaicin research for sensory pharmacology and physiology.
AB  - Capsaicin, the pungent ingredient of chilli peppers has become a "hot" topic in
      neuroscience with yearly publications over half thousand papers. It is outlined
      in this survey how this exciting Hungarian research field emerged from almost
      complete ignorance. From the initial observation of the phenomenon of "capsaicin
      desensitization", a long-lasting chemoanalgesia and impairment in
      thermoregulation against heat, the chain of new discoveries which led to the
      formulation of the existence of a "capsaicin receptor" on C-polymodal nociceptors
      is briefly summarized. Neurogenic inflammation is mediated by these C-afferents
      which are supplied by the putative capsaicin receptor and were termed as
      "capsaicin sensitive" chemoceptive afferents. They opened new avenues in local
      peptidergic regulation in peripheral tissues. It has been suggested that in
      contrast to the classical axon reflex theory, the capsaicin-sensitive sensory
      system subserves a "dual sensory-efferent" function whereby initiation of
      afferent signals and neuropeptide release are coupled at the same nerve endings.
      Furthermore, in the skin at threshold stimuli which do not evoke sensation elicit
      already maximum efferent response as enhanced microcirculation. In isolated organ
      preparations large scale of new type of peptidergic capsaicin-sensitive
      neurogenic smooth muscle responses were revealed after the first one was
      described by ourselves on the guinea-pig ileum in 1978. Recently the "capsaicin
      receptor" has been cloned and it is now named as the "transient receptor
      potential vanilloid 1" (TRPV1). Hence, capsaicin research led to the discovery of
      the first temperature-gated ion channel gated by noxious heat, protons,
      vanilloids and endogenous ligands as anandamide, N-oleoyldopamine and
      lipoxygenase products. Another recent achievement is the discovery of a novel
      "unorthodox" neurohumoral regulatory mechanism mediated by somatostatin.
      Somatostatin released from the TRPV1-expressing nerve endings reaches the
      circulation and elicits systemic antiinflammatory and analgesic "sensocrine"
      functions with counter-regulatory influence e.g. in Freund's adjuvant-induced
      chronic arthritis. Nociceptors supplied by TRPV1 and sst4 somatostatin receptors
      has become nowadays promising targets for drug development.

PMID- 15567474
TI  - A novel action of stargazin as an enhancer of AMPA receptor activity.
AB  - Stargazin (gamma-2) is disrupted in the ataxic and epileptic mutant mouse,
      stargazer (stg). The striking defect in the stg cerebellum is the lack of
      functional AMPA receptors on granule cells. Recently, it has been reported that
      gamma-2 and its related molecules are crucial for the surface expression,
      synaptic targeting and recycling of AMPA receptors, being termed collectively as
      the transmembrane AMPA receptor regulatory proteins (TARPs). However, it is still
      unclear whether TARPs directly modulate AMPA receptor activity. Here we report
      that coexpression of GluRalpha1 (GluR1) with gamma-2 using HEK293 cells and
      Xenopus oocytes markedly enhanced glutamate-induced currents. This effect was far
      beyond the increase of AMPA receptor surface expression and accompanied by
      increased glutamate affinity and subunit cooperativity. Other member of TARPs
      (gamma-3, gamma-4, and gamma-8) also enhanced the current response through the
      AMPA receptors. The enhancing effect by gamma-2 coexpression was further observed
      for homomeric GluRalpha2 (GluR2) channels, which, when expressed alone, are known
      to produce only a small or negligible current response. These results suggest
      that gamma-2 not only promotes AMPA receptor surface expression but also directly
      modulates AMPA receptor activity.

PMID- 15567475
TI  - Ketogenic diet fed rats have low levels of S100B in cerebrospinal fluid.
AB  - Ketogenic diets have been used to treat seizure disorders of children resistant
      to conventional anti-epileptic drug treatment. The mechanism of action of this
      diet, however, is unknown. Gliosis is a very common characteristic in tissues
      associated with epileptogenesis and glial cytokines may be involved in the
      pathology of seizure disorders. We investigate herein, whether ketogenic diet fed
      rats demonstrate changes in the immunocontent of S100B, an astrocyte-derived
      cytokine elevated in the temporal lobe of refractory epilepsy. Lower levels of
      S100B were observed in cerebrospinal fluid with no significant changes in S100B
      and GFAP content in brain tissue. Ketogenic fed rats presented a lower seizure
      severity induced by pentylenetetrazole and no change in cerebrospinal fluid S100B
      after pentylenetetrazole administration. These results support the concept that
      the ketogenic diet is neuroprotective in seizure disorders. Since S100B has an
      extracellular activity in neuronal excitability and synaptic plasticity, it would
      be reasonable to conceive that a decrease in the S100B could be involved in the
      mechanism of action of the ketogenic diet. However, it is not possible to
      establish a direct link between reduced CSF S100B and decreased severity of PTZ
      induced attacks at present moment. Regardless of this, CSF S100B could be
      proposed as an index of efficacy of ketogenic diet for seizure disorders.

PMID- 15567476
TI  - Intracellularly labeled pyramidal neurons in the cortical areas projecting to the
      spinal cord. I. Electrophysiological properties of pyramidal neurons.
AB  - To study cortical motor control, we examined electrical characteristics of
      pyramidal neurons in the present report, and intra- or juxta-columnar connections
      of the pyramidal neurons to corticospinal neurons in the accompanying report.
      Pyramidal neurons were intracellularly recorded and stained in slices of rat
      motorsensory cortices (areas FL, HL and M1) where many corticospinal neurons were
      labeled retrogradely. They were morphologically classified into classical, star
      and other modified pyramidal neurons, and electrophysiologically into regular
      spiking (RS), intrinsic bursting (IB) and irregular-spiking (IS) neurons on the
      basis of spiking pattern in response to 500 ms depolarizing current pulses. RS
      responses were further divided into RS with slow adaptation (RS-SA) and RS with
      fast adaptation (RS-FA). The electrical properties were associated with the
      laminar location of the neurons; RS-SA responses were observed frequently in
      layer II/III and less frequently in layers IV-VI, and IB and IS responses were
      exclusively found in layers V and VI, respectively. Interestingly, all layer IV
      neurons in area FL/HL were RS-FA star-pyramidal neurons, whereas layer IV neurons
      in area M1 were RS-SA classical pyramidal neurons. Although weak stimulation of
      areas FL/HL and M1 is known to elicit movement, these results suggest different
      information processings between the two areas.

PMID- 15567477
TI  - Intracellularly labeled pyramidal neurons in the cortical areas projecting to the
      spinal cord. II. Intra- and juxta-columnar projection of pyramidal neurons to
      corticospinal neurons.
AB  - Intra- or juxta-columnar connections of pyramidal neurons to corticospinal
      neurons in rat motorsensory cortices were examined with brain slices by combining
      intracellular staining with Golgi-like retrograde labeling of corticospinal
      neurons. Of 108 intracellularly labeled pyramidal neurons, 27 neurons were
      selected for morphological analysis by successful staining of their axonal
      arborizations and sufficient retrograde labeling of corticospinal neurons. Many
      varicosities of local axon collaterals of each pyramidal neuron were closely
      apposed to the dendrites of corticospinal neurons, suggesting the convergent
      projections of layer II-VI pyramidal neurons to corticospinal neurons.
      Particularly, the varicosities of a layer IV star-pyramidal neuron made two- to
      three-fold more appositions to the dendrites of corticospinal neurons than those
      of a pyramidal neuron in the other layers. Fifteen appositions were examined
      electron-microscopically and 60% of them made asymmetric axospinous synapses. The
      present results together with those of the preceding report suggest that thalamic
      inputs are conveyed to corticospinal neurons preferentially via layer IV star
      pyramidal neurons with phasic response properties, and thereby might contribute
      to the initiation or switching of movement. In contrast, inputs with tonic
      response properties from the other layers seem to be integrated in corticospinal
      neurons, and might be useful in maintaining the activity of corticospinal
      neurons.

PMID- 15567478
TI  - Expression of serotonin2A receptors in Purkinje cells of the developing rat
      cerebellum.
AB  - Previous physiological and pharmacological studies have shown that the
      serotonin2A (5-HT2A) receptor is involved in cerebellar functions. However, the
      expression of 5-HT2A receptors in the developing cerebellum has not been
      elucidated to date. In the present immunohistochemical study, we examined
      developmental changes of the distribution of 5-HT2A receptors in Purkinje cells
      of the rat cerebellum from embryonic day 18 (E18) to postnatal day 21 (P21). The
      weak immunoreaction to 5-HT2A receptors was found in the deep cerebellar nuclei
      on E19. In the cerebellar cortex of the hemisphere and the posterior vermis,
      somata of Purkinje cells became weakly immunoreactive on P0. With the dendritic
      elongation and arborization, the immunoreaction appeared in the proximal parts of
      Purkinje cell dendrites. Distal parts of the dendrites became immunoreactive
      after P12, and were strongly immunolabeled by P21. The present study may provide
      a structural basis to investigate the roles of 5-HT2A receptors during the
      cerebellar development.

PMID- 15567479
TI  - Analysis of human locomotion by recording sole-floor reaction forces from
      anatomically discrete points.
AB  - Sole-floor reaction forces were recorded from five anatomically discrete points
      to analyze characteristics of human locomotion. Strain gauge of 14 mm diameter
      were firmly attached to the sole of bare-foot for recording force changes from
      the following five points: (1) medial process of calcaneus, (2) head of 1st
      metatarsal, (3) head of 3rd metatarsal, (4) head of 5th metatarsal and (5) great
      toe. Fifteen healthy adults were asked to walk at 2, 4, 6 and 8 km/h and to run
      at 8 km/h on the treadmill. Sole-floor reaction forces from 1st to 5th
      metatarsals show reciprocal changes during stance phase, while force from 1st
      metatarsal is strong 5th metatarsal shows weak reaction and vice versa. This
      phenomenon may be an expression of locomotor program to maintain vertical
      stability of the body during stance phase. There was a linear relation between
      walking speeds and sum of force from the five points, although sum of forces from
      three metatarsals did not change significantly during the walking speeds,
      indicating mainly calcaneus and great toe contribute to increasing walking speed.
      During running the sum of force from the three metatarsals increased sharply,
      joining the other two points to increase thrust.

PMID- 15567480
TI  - Two different effects of transcranial magnetic stimulation to the human motor
      cortex during the pre-movement period.
AB  - A single-pulse TMS to the human motor cortex (M1) influences reaction time (RT).
      We may summarize from previous studies where different groups of subjects
      participated in various types of RT tasks that TMS above motor threshold (MT)
      delays RT, whereas TMS below MT shortens RT and that these RT changes depends on
      TMS timings during RT period. However, these effects have never been
      systematically investigated in a single study where an identical group of
      subjects participated. The purpose of this study is to test previous TMS effects
      in a study of simple RT task. Seven subjects isometrically abducted their right
      index fingers as quickly as possible when a visual stimulus appeared. A single
      pulse TMS was randomly delivered over the left M1 at various timings during RT
      period in a single trial (at 0, 40, 60, 80 or 100 ms after the visual stimulus).
      Motor-evoked potential (MEP) and EMG activity for response were recorded from the
      right finger muscles. Only the TMS above MT delivered at 80 or 100 ms, which
      increased MEP amplitude, significantly delayed RT and increased the size of
      response EMG activities that may reflect contents of central motor commands. The
      TMS below MT at these timings, which occasionally evoked MEP, exclusively
      shortened RT despite the fact that the response EMG size was unchanged. A single
      pulse TMS has different effects on the ongoing neuronal processes in M1 during
      the pre-movement period: TMS above MT may temporally retard the processes and
      also affect contents of central motor commands, whereas TMS below MT may simply
      facilitate its processes without affecting motor commands.

PMID- 15567481
TI  - System L-amino acid transporters are differently expressed in rat astrocyte and
      C6 glioma cells.
AB  - The system L-amino acid transporter is a major nutrient transport system that is
      responsible for Na+-independent transport of neutral amino acids including
      several essential amino acids. We have compared and examined the expressions and
      functions of the system L-amino acid transporters in both rat astrocyte cultures
      and C6 glioma cells. The rat astrocyte cultures expressed the l-type amino acid
      transporter 2 (LAT2) with its subunit 4F2hc, whereas the l-type amino acid
      transporter 1 (LAT1) was not expressed in these cells. The C6 glioma cells
      expressed LAT1 but not LAT2 with 4F2hc. The [14C]l-leucine uptakes by the rat
      astrocyte cultures and C6 glioma cells were Na+-independent and were completely
      inhibited by the system l selective inhibitor, BCH. These results suggest that
      the transport of neutral amino acids including several essential amino acids into
      rat astrocyte cultures and C6 glioma cells are for the most part mediated by LAT2
      and LAT1, respectively. Therefore, the rat astrocyte cultures and C6 glioma cells
      are excellent tools for examining the properties of LAT2 and LAT1, respectively.
      Moreover, the specific inhibition of LAT1 in cancer cells might be a new
      rationale for anti-cancer therapy.

PMID- 15567482
TI  - Extrasynaptic localization of GABA in the developing mouse cerebellum.
AB  - In the adult brain, gamma-amino butyric acid (GABA) is synaptically released and
      mediates inhibitory transmission. Recent studies have revealed that GABA is a
      trophic factor for brain development. To reveal the distribution of GABA and its
      secretion mechanisms during brain development, we investigated the
      immunohistochemical localization of two molecules, GABA and vesicular GABA
      transporter (VGAT), which is a GABAergic vesicle protein, in the developing mouse
      cerebellum by means of newly developed antibodies. Furthermore, we tested the
      relationship between developmental changes in distribution of above two molecules
      in the presynapses and ontogeny of GABAergic synapses. GABAergic synapses were
      detected by immunohistochemistry for the GABA(A) receptor alpha1 subunit, which
      is an essential subunit for inhibitory synaptic transmission in the mature
      cerebellar cortex. Until postnatal day 7 (P7), GABA was localized throughout the
      GABAergic neurons, and VGAT accumulated at axon varicosities and growth cones,
      where the alpha1 subunit did not accumulate. After P10, both GABA and VGAT became
      confined to the terminal sites where the alpha1 subunit was localized. These
      results suggested that GABA was extrasynaptically released from axon varicosities
      and growth cones by vesicular secretion 'exocytosis' and from all parts of
      GABAergic neurons during the cerebellar development by non-vesicular secretion
      'diacrine'.

PMID- 15567483
TI  - Distribution and in situ proliferation patterns of intravenously injected
      immortalized human neural stem-like cells in rats with focal cerebral ischemia.
AB  - Neural stem cells are considered as a candidate for cell replacement therapy in
      various neurological diseases. To investigate whether human neural stem cells can
      migrate into the adult ischemic rat brain, we transplanted immortalized human
      neural 'tem-like' cells intravenously 24 h after focal cerebral ischemia. The
      intravenously injected human neural stem-like cells were found around the
      infarcted area, differentiated into neurons and astrocytes in the lesioned areas,
      and survive up to 56 days after transplantation. The number of the injected cells
      increased between 7 and 14 days after transplantation with incorporating BrdU.
      Our findings show that intravenously injected human neural stem-like cells may
      incorporate into the ischemic brain, and undergo proliferation responding to the
      endogenous mitotic signal during the acute period of focal ischemia.

PMID- 15567484
TI  - Glycolysis regulates the induction of lactate utilization for synaptic potentials
      after hypoxia in the granule cell of guinea pig hippocampus.
AB  - Lactate is considered an alternative substrate that is capable of replacing
      glucose in maintaining synaptic function in adult neurons. But, we found recently
      that lactate could be utilized for maintenance of synaptic potentials only after
      the activation of NMDA and voltage-dependent-calcium channel during glucose
      deprivation. To clarify more on the relationship between glycolysis and induction
      of lactate utilization, we tested lower concentration of glucose with hypoxia to
      induce a relative shortage of anaerobic energy production. Population spikes are
      not maintained with lactate following hypoxia in 10 mM glucose medium, but are
      maintained at their original levels with lactate after exposure to hypoxia in
      lower concentration (5 mM) of glucose. Hypothermia during low glucose-hypoxia,
      bath application of the NMDA channel blocker and the voltage-sensitive calcium
      channel blocker, as well as the omission of extracellular calcium prevented the
      induction of the lactate-supported population spikes. ATP levels in the tissue
      slices are relatively preserved in the conditions that block the induction of
      lactate-supported population spikes. From these observations, we propose that the
      energy source for maintenance of synaptic function in adult neuron changes from
      adult form (glucose alone) to immature one (glucose and/or lactate) after short
      of glucose supply.

PMID- 15567485
TI  - Dominance of the left oblique view in activating the cortical network for face
      recognition.
AB  - Faces in portraits are often depicted from the left 3/4 view (an oblique view of
      the face that is intermediate between the frontal view and left profile). Here,
      we used functional magnetic resonance imaging (fMRI) to show that, compared with
      photographs of right 3/4 views of familiar faces, photographs of left 3/4 views
      of the same faces elicited stronger neural responses in the right middle
      occipital/inferior parietal cortex, and right inferior frontal gyrus; which are
      known to be involved in face recognition. By contrast, there was no differential
      activation in the temporal cortex including the superior temporal sulcus and
      fusiform gyrus, which are thought to process face-related visual stimuli at a
      stage that precedes recognition. We suggest that the preference for the left 3/4
      view of faces was produced at a later stage of facial information processing that
      involves attention or memory retrieval.

PMID- 15567486
TI  - Immunohistochemical study of hnRNP B1 in the postmortem temporal cortices of
      patients with Alzheimer's disease.
AB  - In order to examine the post-transcriptional regulations in Alzheimer's disease,
      we employed immunohistochemical techniques and examined the expression of
      heterogeneous nuclear ribonucleoprotein (hnRNP) B1 in the inferior temporal
      cortex of subjects with Alzheimer's disease. In the mild cases, intense B1
      immunoreactivity was observed in neurons of layer V, and less intense
      immunoreactivity was observed in layers II and III. The overall distributions and
      intensities of B1 immunoreactivity were undistinguishable among mild, moderate,
      and severe cases. Double-immunolabeling with MC1 and B1 demonstrated that B1
      immunoreactivity was preserved in the majority of neurofibrillary tangle (NFT)
      bearing neurons. Our study suggests that hnRNP B1-associated post-transcriptional
      regulations are preserved in the inferior temporal cortex of Alzheimer's disease.

PMID- 15567487
TI  - N(omega)-nitro-L-arginine methyl ester attenuates lithium-induced c-Fos, but not
      conditioned taste aversion, in rats.
AB  - Lithium chloride (LiCl) at doses sufficient to induce conditioned taste aversion
      (CTA) causes c-Fos expression in the relevant brain regions and activates the
      hypothalamic-pituitary-adrenal (HPA) axis. It has been suggested that nitric
      oxide (NO) in the central nervous system may play a role not only in the
      activation of HPA axis but also in CTA learning, and that LiCl may activate the
      brain NO system. To determine the role of NO in lithium-induced CTA, we examined
      the lithium-induced CTA, brain c-Fos expression, and plasma corticosterone level
      with Nomega-nitro-L-arginine methyl ester (L-NAME) pretreatment. Intraperitoneal
      L-NAME (30 mg/kg) given 30 min prior to LiCl significantly decreased lithium
      induced c-Fos expression in the brain regions implicated in CTA learning, such as
      the hypothalamic paraventricular nucleus (PVN), central nucleus of amygdala
      (CeA), and nucleus tractus of solitarius. However, either the lithium-induced CTA
      acquisition or the increase in plasma corticosterone was not attenuated by l-NAME
      pretreatment. These results suggest that NO may be involved in lithium-induced
      neuronal activation of the brain regions, but not in the CTA acquisition or the
      HPA axis activation.

PMID- 15567488
TI  - Two types of acid-sensing ion channel currents in rat hippocampal neurons.
AB  - Two types of acid-sensing ion channel (ASIC)-like currents in cultured rat
      hippocampal neurons were recorded and their characteristics were studied by using
      a whole-cell recording technique. The results revealed that the ASIC-like
      currents, induced by a quick drop of the extracellular pH, decayed with different
      time constants (tau) of 229 +/- 16 (Type I) and 1209 +/- 56 ms (Type II). The
      ASIC-like currents displayed different sensitivities to extracellular proton
      (pH0.5 was 6.17 +/- 0.04 for Type I and 5.70 +/- 0.07 for Type II) and amiloride,
      a specific ASIC channel blocker (IC50 was 1.19 +/- 0.37 microM for Type I and
      0.14 +/- 0.02 microM for Type II). Among all the 360 recorded neurons, ASIC-like
      currents were induced in 314 neurons (87.2%). In the neurons expressing ASICs,
      Type I currents were evoked from 269 neurons (85.7%) and Type II currents were
      induced only from 45 neurons (14.3%). As these ASIC-like currents presented
      various electrophysiological and pharmacological properties, further experiments
      should be conducted to decipher the complex subunit composition of ASICs in the
      hippocampus.

PMID- 15567489
TI  - Mechanisms of enveloped virus release.

PMID- 15567490
TI  - Retrovirus budding.
AB  - The release of retrovirus particles from the infected cell is greatly stimulated
      by short motifs, known as "late" or "L" domains, present within the Gag precursor
      protein. Three distinct classes of L domains have been identified; these bear the
      core sequence: Pro-Thr/Ser-Ala-Pro [P(T/S)AP], Pro-Pro-x-Tyr (PPxY), or Tyr-Pro-x
      Leu (YPxL). A number of recent studies have demonstrated that L domains function
      by interacting with components of the machinery responsible for sorting cellular
      proteins into the multivesicular body (MVB) pathway. This review traces the
      history of L domain discovery and characterization, and highlights the
      relationship between L domain activity, retrovirus release, and the host
      endosomal sorting machinery.

PMID- 15567491
TI  - Budding of alphaviruses.
AB  - Alphaviruses are small highly ordered enveloped RNA viruses, which replicate very
      efficiently in the infected cell. They consist of a nucleocapsid (NC) and a
      surrounding membrane with glycoproteins. In the NC the positive single stranded
      RNA genome of the virus is enclosed by a T=4 icosahedral shell of capsid (C)
      proteins. The glycoproteins form a second shell with corresponding symmetry on
      the outside of the lipid membrane. These viruses mature by budding at the plasma
      membrane (PM) of the infected cell and enter into new cells by acid-triggered
      membrane fusion in endosomes. The viral glycoprotein consists of two subunits,
      E1, which carries the membrane fusion function, and E2, which suppresses this
      function until acid activation occurs. In the infected cell the RNA replication
      and transcription are confined to the cytoplasmic surface of endosome-derived
      vesicles called cytopathic vacuoles type I (CPV I). These structures are closely
      associated with membranes of the endoplasmic reticulum (ER), thereby creating a
      microenvironment for synthesis of viral proteins, assembly of the glycoproteins
      and formation of genome-C complexes. The budding process of the virus is
      initiated by C-glycoprotein interactions, possibly already before the
      glycoproteins arrive at the PM. This might involve a premade, ordered NC or a
      less ordered form of the genome-C complex. In the latter case, the interactions
      in the glycoprotein shell provide the major driving force for budding. The nature
      of the C-glycoprotein interaction has been resolved at atomic resolution by
      modelling. It involves hydrophobic interactions between a Tyr-X-Leu tripeptide in
      the internal tail of the E2 subunit and a pocket on the surface of the C protein.
      When the virus enters the endosome of a new cell the acid conditions trigger
      rearrangements in the glycoprotein shell, which result in the dissociation of the
      interactions that drive budding and a concomitant activation of the membrane
      fusion function in the E1 subunit.

PMID- 15567492
TI  - Rhabdovirus assembly and budding.
AB  - Rhabdoviruses are a diverse, widely-distributed group of enveloped viruses that
      assemble and bud from the plasma membrane of host cells. Recent advances in the
      identification of domains on both the envelope glycoprotein and the matrix
      protein of rhabdoviruses that contribute to virus assembly and release have
      allowed us to refine current models of rhabdovirus budding and to describe in
      better detail the interplay between both viral and cellular components involved
      in the budding process. In this review we discuss the steps involved in
      rhabdovirus assembly beginning with genome encapsidation and the association of
      nucleocapsid-matrix protein pre-assembly complexes with the inner leaflet of the
      plasma membrane, how condensation of these complexes may occur, how microdomains
      containing the envelope glycoprotein facilitate bud site formation, and how
      multiple forms of the matrix protein may participate in virion extrusion and
      release.

PMID- 15567493
TI  - Molecular mechanism of paramyxovirus budding.
AB  - Components of paramyxoviruses are assembled at the plasma membrane of infected
      cells, and progeny viruses are formed by the budding process. Although the
      molecular mechanisms that drive budding (membrane curving and "pinching-off"
      reaction) are not well understood, the viral matrix (M) protein is thought to
      play a major role in the process. The M protein forms a dense layer tightly
      associated with the inner leaflet of the plasma membrane of infected cells.
      Expression of the M protein of some paramyxoviruses results in the formation and
      release of virus-like particles that contain the M protein; thus, in these
      viruses, the M protein alone can apparently trigger all steps required for the
      formation and release of virus-like particles. M also interacts specifically with
      viral envelope glycoproteins and nucleocapsids and is involved in directed
      transport of viral components to the budding site at the apical surface of
      polarized cells. In addition, protein-protein interactions between M and the
      cytoplasmic tail of viral glycoproteins and between M and the nucleocapsid affect
      the efficiency of virus production. The structural organization of the virion and
      the functions of the M protein clearly indicate that this protein orchestrates
      the budding of paramyxovirus.

PMID- 15567494
TI  - Assembly and budding of influenza virus.
AB  - Influenza viruses are causative agents of an acute febrile respiratory disease
      called influenza (commonly known as "flu") and belong to the Orthomyxoviridae
      family. These viruses possess segmented, negative stranded RNA genomes (vRNA) and
      are enveloped, usually spherical and bud from the plasma membrane (more
      specifically, the apical plasma membrane of polarized epithelial cells). Complete
      virus particles, therefore, are not found inside infected cells. Virus particles
      consist of three major subviral components, namely the viral envelope, matrix
      protein (M1), and core (viral ribonucleocapsid [vRNP]). The viral envelope
      surrounding the vRNP consists of a lipid bilayer containing spikes composed of
      viral glycoproteins (HA, NA, and M2) on the outer side and M1 on the inner side.
      Viral lipids, derived from the host plasma membrane, are selectively enriched in
      cholesterol and glycosphingolipids. M1 forms the bridge between the viral
      envelope and the core. The viral core consists of helical vRNP containing vRNA
      (minus strand) and NP along with minor amounts of NEP and polymerase complex (PA,
      PB1, and PB2). For viral morphogenesis to occur, all three viral components,
      namely the viral envelope (containing lipids and transmembrane proteins), M1, and
      the vRNP must be brought to the assembly site, i.e. the apical plasma membrane in
      polarized epithelial cells. Finally, buds must be formed at the assembly site and
      virus particles released with the closure of buds. Transmembrane viral proteins
      are transported to the assembly site on the plasma membrane via the exocytic
      pathway. Both HA and NA possess apical sorting signals and use lipid rafts for
      cell surface transport and apical sorting. These lipid rafts are enriched in
      cholesterol, glycosphingolipids and are relatively resistant to neutral detergent
      extraction at low temperature. M1 is synthesized on free cytosolic polyribosomes.
      vRNPs are made inside the host nucleus and are exported into the cytoplasm
      through the nuclear pore with the help of M1 and NEP. How M1 and vRNPs are
      directed to the assembly site on the plasma membrane remains unclear. The likely
      possibilities are that they use a piggy-back mechanism on viral glycoproteins or
      cytoskeletal elements. Alternatively, they may possess apical determinants or
      diffuse to the assembly site, or a combination of these pathways. Interactions of
      M1 with M1, M1 with vRNP, and M1 with HA and NA facilitate concentration of viral
      components and exclusion of host proteins from the budding site. M1 interacts
      with the cytoplasmic tail (CT) and transmembrane domain (TMD) of glycoproteins,
      and thereby functions as a bridge between the viral envelope and vRNP. Lipid
      rafts function as microdomains for concentrating viral glycoproteins and may
      serve as a platform for virus budding. Virus bud formation requires membrane
      bending at the budding site. A combination of factors including concentration of
      and interaction among viral components, increased viscosity and asymmetry of the
      lipid bilayer of the lipid raft as well as pulling and pushing forces of viral
      and host components are likely to cause outward curvature of the plasma membrane
      at the assembly site leading to bud formation. Eventually, virus release requires
      completion of the bud due to fusion of the apposing membranes, leading to the
      closure of the bud, separation of the virus particle from the host plasma
      membrane and release of the virus particle into the extracellular environment.
      Among the viral components, M1 contains an L domain motif and plays a critical
      role in budding. Bud completion requires not only viral components but also host
      components. However, how host components facilitate bud completion remains
      unclear. In addition to bud completion, influenza virus requires NA to release
      virus particles from sialic acid residues on the cell surface and spread from
      cell to cell. Elucidation of both viral and host factors involved in viral
      morphogenesis and budding may lead to the development of drugs interfering with
      the steps of viral morphogenesis and in disease progression.

PMID- 15567495
TI  - Budding events in herpesvirus morphogenesis.
AB  - Herpes virions are complex particles that consist of more than 30 different
      virally encoded proteins. The molecular basis of how this complicated structure
      is assembled is only recently beginning to emerge. After replication in the host
      cell nucleus viral DNA is incorporated into preformed capsids, which leave the
      nucleus by a first budding event at the inner nuclear membrane resulting in the
      formation of primary enveloped virions in the perinuclear space. The primary
      envelope then fuses with the outer leaflet of the nuclear membrane thereby
      releasing nucleocapsids into the cytoplasm. Final envelopment, including the
      acquisition of more than 15 tegument and more than 10 envelope (glyco) proteins
      occurs by budding into Golgi-derived vesicles. Mature virions are released after
      fusion of the vesicle membrane with the plasma membrane of the cell. Thus,
      herpesvirus morphogenesis requires two different budding steps, which are
      distinct not only in the subcellular compartments in which they occur but also by
      the viral proteins involved. This review summarizes recent advances in our
      understanding of the two herpesvirus budding events.

PMID- 15567496
TI  - Filovirus budding.
AB  - Family Filoviridae, which includes Ebola virus (EBOV) and Marburg virus (MARV),
      is a growing threat to human and non-human primate populations in central Africa.
      Although many facets of the filovirus life cycle remain to be deciphered, a great
      deal has been learned in recent years. In particular, a clearer understanding of
      the roles played by viral, as well as cellular, proteins in the assembly and
      budding processes has been achieved. This review will discuss the current state
      of filovirus budding research, with especial emphasis placed on the viral matrix
      protein VP40 and its relationship with the cellular vesicular sorting pathway.
      Possible budding functions of the viral glycoprotein (GP), as well as the
      membrane-associated viral protein 24 (VP24), will also be described, and a model
      for filovirus budding will be proposed.

PMID- 15567497
TI  - The exit of vaccinia virus from infected cells.
AB  - Vaccinia virus (VACV) is the prototypic member of the Poxviridae a group of large
      DNA viruses that replicate in the cell cytoplasm. The entry and exit of VACV are
      complicated by the existence of two distinct forms of virus, intracellular mature
      virus (IMV) and extracellular enveloped virus (EEV), that are surrounded by
      different numbers of lipid membranes and have different surface proteins. Here
      the mechanisms used by these different forms of VACV to leave the infected cell
      are reviewed. Whereas some enveloped viruses complete virus assembly by budding
      through the plasma membrane, infectious poxvirus particles (IMV) are produced
      within the cytoplasm. These particles are either further enveloped by
      intracellular membranes to form intracellular enveloped virus (IEV) that are
      transported to the cell surface on microtubules and exposed on the cell surface
      by exocytosis, or are released after cell lysis. If the enveloped virion remains
      attached to the cell surface it is called cell-associated enveloped virus (CEV)
      and is propelled into surrounding cells by growing actin tails beneath the plasma
      membrane. Alternatively, the surface virion may be released as EEV.

PMID- 15567498
TI  - Envelopment of the hepatitis B virus nucleocapsid.
AB  - The hepatitis B virus (HBV) is an enveloped DNA virus with an icosahedral capsid
      replicating via reverse transcription. The crystal structure of the capsid is
      known. It has a diameter of 36 nm and is formed by one protein species (C
      protein). The viral envelope contains three different coterminal proteins (S, M,
      and L proteins) spanning the membrane several times. These proteins are not only
      released from infected cells as components of the viral envelope but in 10,000
      fold excess as subviral lipoprotein particles with a diameter of 22 nm containing
      no capsid. Assembly of the capsid occurs in the cytosol and results in packaging
      of a 3.5 kb RNA molecule together with viral and cellular factors. This newly
      formed capsid cannot be enveloped. Rather, synthesis of the viral DNA genome in
      the lumen of the capsid by reverse transcription is required to induce a budding
      competent state. Envelopment then takes place at an intracellular membrane of the
      pre-Golgi compartment. The S and the L protein, but not the M protein, is
      required for this process. The L protein forms two different transmembrane
      topologies. The isoform exposing the N-terminal part at the cytosolic side of the
      membrane is essential for budding. In this domain, a 22 amino acid (aa) long
      linear stretch has been mapped genetically to play a vital role in the
      morphogenetic process. This domain probably mediates the contact to the capsid. A
      second matrix domain was mapped to the cytosolic loop of the S protein. A similar
      genetic approach identified two small areas on the capsid surface, which might
      interact with the envelope proteins during envelopment.

PMID- 15567499
TI  - Novel strategic therapeutic approaches for prevention of local recurrence of
      pancreatic cancer after resection: trans-tissue, sustained local drug-delivery
      systems.
AB  - Local recurrence and hepatic metastasis are still the major causes of death of
      patients who have undergone resection for pancreatic cancer. To decrease the
      incidence of local recurrence, we have proposed and devised several trans-tissue
      and local delivery systems, all of which could be applied immediately after
      surgery at the resected sites: (1) System I: a drug-loaded photocured gelatinous
      tissue-adhesive gel (bioactive substance reservoir) that enables the sustained
      release of a drug, protein, or gene-encoding adenovirus, (2) System II: an anti
      cytokine antibody-fixed photocured gelatinous, tissue-adhesive gel (cytokine
      barrier) that prevents cytokine permeation into the resected tissue, (3) System
      III: a gene-modified cell sheet that enables the sustained release of a very
      costly protein produced by gene-transduced cells and (4) System IV: a
      percutaneous drug-delivery device that enables continuous drug infusion and easy
      removal from the body. This review article is a summary of our several years of
      efforts and attempts, which are composed of integrated disciplines including
      active biomaterials and genetic- and tissue-engineerings, to overcome the
      recurrence of pancreatic cancer. Here, we outline our proposed strategies and
      therapeutic devices/materials and discuss their potential therapeutic
      effectiveness, promises and challenges in the clinical settings.

PMID- 15567500
TI  - Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes
      containing lipophilic gemcitabine prodrugs.
AB  - Gemcitabine is a known anticancer agent rapidly deaminated to the inactive
      metabolite 2',2'-difluorodeoxyuridine; it must therefore be administered at very
      high dose. Many different approaches have been tried to improve the metabolic
      stability; we synthesized a series of increasingly lipophilic prodrugs of
      gemcitabine by linking the 4-amino group with valeroyl, heptanoyl, lauroyl and
      stearoyl linear acyl derivatives. We studied their stability at storage, in
      plasma and with the lysosomal intracellular enzyme cathepsins. We studied
      incorporation of these lipophilic prodrugs in liposomes, where their
      encapsulation efficiency (EE) closely depends on the length of the saturated 4
      (N)-acyl chain, the phospholipids chosen and the presence of cholesterol. A
      maximum EE of 98% was determined for 4-(N)-stearoyl-gemcitabine incorporated in
      DSPC/DSPG 9:1. This formulation was correlated with the highest stability in
      vitro and in vivo. Cytotoxicity of gemcitabine prodrugs, free or encapsulated in
      liposomes, was between two- and sevenfold that of free gemcitabine. Encapsulation
      of long-chain lipophilic prodrugs of gemcitabine in liposomes protected the drug
      from degradation in plasma, assuring a long plasma half-time and intracellular
      release of the free drug.

PMID- 15567501
TI  - In vitro degradation of nanoparticles prepared from polymers based on DL-lactide,
      glycolide and poly(ethylene oxide).
AB  - Nanoparticles of poly(DL-lactic acid) (PDLLA), poly(DL-lactic-co-glycolic acid)
      (PLGA) and poly(ethylene oxide)-PLGA diblock copolymer (PEO-PLGA) were prepared
      by the salting-out method. The in vitro degradation of PDLLA, PLGA and PEO-PLGA
      nanoparticles in PBS (pH 7.4) at 37 degrees C was studied. The particle size,
      molecular weight of the polymers and the amount of lactic and glycolic acids
      formed were followed in time. PDLLA nanoparticles gradually degraded over a
      period of 2 years and retain their size during that period. A faster degradation
      was observed for PLGA nanoparticles, which was nearly complete after 10 weeks.
      PLGA nanoparticles retained their size during that period. In PEO-PLGA
      nanoparticles, the ester bond connecting the PEO and the PLGA segments was
      preferentially cleaved, which led to a relatively fast decrease in molecular
      weight and to (partial) aggregation, as multimodal size distributions were
      observed. PEO-PLGA nanoparticles were almost completely degraded within 8 weeks.

PMID- 15567502
TI  - Conjugation of an antibody to cross-linked fibrin for targeted delivery of anti
      restenotic drugs.
AB  - There is an urgent need to treat restenosis, a major complication of the
      treatment of arteries blocked by atherosclerotic plaque, using local delivery
      techniques. We observed that cross-linked fibrin (XLF) is deposited at the site
      of surgical injury of arteries. An antibody to XLF, conjugated to anti-restenotic
      agents, should deliver the drugs directly and only to the site of injury. An anti
      XLF antibody (H93.7C.1D2/48; 1D2) was conjugated to heparin (using N-succinimidyl
      3-(2-pyridyldithio)propionate), low molecular weight heparin (LMWH) (adipic acid
      dihydrazide) and rapamycin (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N
      hydroxysuccinimide), and the conjugates purified and tested for activity before
      use in vivo. Rabbits had their right carotid arteries de-endothelialised and then
      given a bolus of 1D2-heparin, 1D2-LMWH or 1D2-rapamycin conjugate or controls of
      saline, heparin, LMWH, rapamycin or 1D2 (+/-heparin bolus) and sacrificed after 2
      or 4 weeks (12 groups, n=6/group). Rabbits given any of the conjugates had
      minimal neointimal development in injured arteries, with up to 59% fewer
      neointimal cells than those given control drugs. Rabbits given 1D2-heparin or 1D2
      LMWH had an increased or insignificant reduction in luminal area, with positive
      remodelling, while the medial and total arterial areas of rabbits given 1D2
      rapamycin were not affected by injury. Arteries exposed to 1D2-heparin or 1D2
      rapamycin had more endothelial cells than rabbits given control drugs. Thus, XLF
      antibodies can site-deliver anti-restenotic agents to injured areas of the artery
      wall, where the conjugates can influence remodelling, re-endothelialisation and
      neointimal cell density, with reduced neointimal formation.

PMID- 15567503
TI  - A new microencapsulation method using an ultrasonic atomizer based on interfacial
      solvent exchange.
AB  - Reservoir-type microcapsules were produced in a mild and highly efficient manner
      using a coaxial ultrasonic atomizer. To understand the microencapsulation
      mechanism, the atomizer was operated in different modes. The results suggested
      the reservoir-type microcapsules were formed by midair collision of the
      microdrops of the two component liquids consisting of a polymer solution and an
      aqueous solution. The encapsulation efficiency and the distribution of the
      microdrops captured in midair were dependent on the ratio of the flow rates of
      the two liquids, which suggested that the collision involved multiple microdrops.
      This method allowed lysozyme to be encapsulated without loss of functional
      integrity and to be released with near zero-order kinetics for over 50 days. The
      ultrasonic atomizer provided a new method of preparing reservoir-type
      microcapsules.

PMID- 15567504
TI  - Distribution kinetics of a micelle-forming block copolymer Pluronic P85.
AB  - Pluronic block copolymers, micelle-forming polymeric surfactants, are currently
      being evaluated in chemotherapy clinical trials in combination with doxorubicin
      to treat multidrug-resistant (MDR) tumors. This study examines the
      pharmacokinetics and biodistribution of Pluronic P85 (P85), a potent inhibitor of
      P-glycoprotein (Pgp). P85 was radioactively labeled and administered
      intravenously (i.v.) to mice. The concentration of the copolymer was varied to
      examine the effects of micelle formation on the distribution kinetics. The main
      pharmacokinetic parameters (the area under the curve, half-life, clearance, mean
      residence time, and volume of distribution) were determined. The results suggest
      that half-life of P85 varies from 60 to 90 h, depending on its aggregation state.
      Formation of micelles decreased the uptake of the block copolymer in the liver.
      However, it had no effect on the total clearance, suggesting that the elimination
      of P85 was controlled by the renal elimination of P85 unimers and not by the rate
      of micelle disposition or disintegration. The total clearance value suggests that
      a significant portion of P85 is reabsorbed back into the blood, probably through
      the kidney's tubular membranes.

PMID- 15567505
TI  - Intercalation, delivery, and expression of the gene encoding green fluorescence
      protein utilizing nanobiohybrids.
AB  - Non-viral gene vectors have attracted much attention recently due to setbacks
      with viral delivery systems. Here a new non-viral delivery system based on
      nanobiohybrids synthesized by the intercalation of a full gene and promoter
      encoding Green Fluorescent Protein (GFP) between the layers of an inorganic host
      is reported. The nanobiohybrids were delivered to 9L glioma cells, JEG3
      choriocarcinoma placental cells, and cardiac myocytes. All cells were able to
      internalize and tolerate the nanobiohybrids. In addition, all cells expressed the
      gene with some cell lines having up to 90% transfection efficiency. This new, bio
      mimetic delivery system shows promise for use in non-viral gene therapy.

PMID- 15567506
TI  - Comparison of antisense oligonucleotide drug delivery systems.
AB  - Antisense oligonucleotides (AS-ONs) are specific drugs to inhibit gene expression
      at the transcriptional level. They possess a poor bioavailability and can be
      degraded by nucleases very rapidly. Therefore, a strong need for the development
      of oligonucleotide drug delivery systems exists. In the present study, two
      commercially available liposomes (DOTAP, lipofectin), one artificial virus
      capsoid (polyoma VP1), two cationic acrylate nanoparticles and two protamine
      based nanoparticle preparations (proticles) were compared. Physical parameters of
      all carrier systems including z-average size, size distribution and surface
      charge regarding were determined. Cellular uptake was measured by a microplate
      fluorescence quantification method and, in addition, was visualized in mouse
      fibroblasts by confocal laser scan microscopy (CLSM). A comparison of
      cytotoxicity of the different drug delivery systems was performed in vitro using
      a MTT assay. Mouse fibroblasts which were stable transfected with the cDNA of a N
      methyl-D-aspartate (NMDA) receptor also served as functional antisense
      oligonucleotide test system based on excitotoxicity (cell death). In addition,
      the efficiency of our oligonucleotide delivery systems was compared on the level
      of protein expression by Western blotting. Concluding the results, an increased
      uptake of the ON was found (2-18-fold) for all delivery systems compared to the
      free ON. Protamine-based nanoparticles showed a very low cytotoxicity in
      contradiction to all other carrier systems. Lipofectin could be identified as the
      most potent delivery system in terms of antisense effect, followed by protamine
      nanoparticles and DOTAP. Sequence-specific antisense effects up to 80% were
      observed in the functional cell death assay. The highest reduction of NMDA
      expression was obtained from liposomal preparations with approximately 60%
      analyzed by Western blot.

PMID- 15567507
TI  - Modified polyethylenimines as non viral gene delivery systems for aerosol
      therapy: effects of nebulization on cellular uptake and transfection efficiency.
AB  - This study examined the effect of nebulization on the cellular uptake and
      transfection efficiency of polyplexes from four polyethylenimine (PEI)
      modifications: branched 25 kDa PEI (bPEI), linear 22 kDa PEI (linPEI), pegylated
      PEI (pegPEI) and biodegradable PEI (bioPEI). Polyplexes were aerosolized with air
      jet and ultrasonic nebulizers. The aerosol was collected and used to determine
      complex size and zeta potential. Fluorescence-assisted cell sorting (FACS) was
      used to quantify the cellular association of polyplexes in primary alveolar cells
      (AEC), A549 cells and primary bronchial cells (BEC). Confocal laser scanning
      microscopic images provided information about the internalization of polyplexes.
      Transfection efficiencies of polyplexes were quantified via measurement of
      luciferase expression. All polymers were stable during nebulization, although
      size increases were observed after air-jet nebulization. FACS studies showed a
      two- to three-fold increase in polyplex association with BEC compared to A549
      cells, while polyplex association with AEC was negligible. BPEI, linPEI and
      bioPEI polyplexes were internalized, while pegPEI polyplexes remained
      predominately attached to the cellular membrane. Luciferase expression was
      detected only in BEC and A549 cells with transfection efficiencies approximately
      one order of magnitude higher in BEC. All PEI modifications investigated were
      suitable for aerosol therapy, although cell type and polymer structure
      significantly influenced the uptake and transfection efficiency of the
      polyplexes.

PMID- 15567508
TI  - Modified polyethylenimines as non-viral gene delivery systems for aerosol gene
      therapy: investigations of the complex structure and stability during air-jet and
      ultrasonic nebulization.
AB  - Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising
      non-viral delivery systems for pulmonary inhalation gene therapy and thus require
      sufficient stability during nebulization. The structure and stability of four
      different PEI-DNA polyplexes, namely branched (bPEI), linear (linPEI),
      poly(ethylene glycol)-grafted PEI (PEGPEI), biodegradable (bioPEI) PEI with DNA,
      were investigated. Using atomic force microscopy, the morphology of DNA and
      polyplexes before and after both air-jet and ultrasonic nebulization was
      characterized. The influence of nebulization on physico-chemical properties,
      particle size and zeta potential, was studied. Efficient DNA condensation to
      spherical particles was achieved with bPEI (90 nm) and PEGPEI (110 nm). By
      contrast, incomplete DNA condensations, seen as flower structures, were observed
      with linPEI (110 nm) and bioPEI (105 nm). Air-jet nebulization altered the
      polyplex structure to a greater extent than ultrasonic nebulization and resulted
      mainly in smaller and non-spherical particles (30-200 nm). Ultrasonic
      nebulization did not change the spherical structure or particle size of the
      polyplexes. In particular, the shape and size of the PEGPEI polyplexes did not
      change. We conclude that ultrasonic nebulization is a milder aerosolization
      method for gene delivery systems based on PEI. Additionally, PEGPEI-DNA
      polyplexes seem to be more stable than their counterparts, which may be
      advantageous in pulmonary inhalation gene therapy.

PMID- 15567509
TI  - Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of
      polystyrene nanosphere: implications for rational design of nanoparticles.
AB  - We evaluated the in vivo disposition characteristics of polystyrene nanospheres
      (NS) with the particle size of 50 nm (NS-50) pre-coated with human serum albumin
      (HSA) after intravenous administration in rats. HSA-coated NS-50 showed much
      longer blood-circulating property and the hepatic uptake clearance for HSA-coated
      NS-50 was about 1/5 of that for NS-50. In parallel with the results obtained in
      the in vivo study, liver perfusion experiments also showed that the hepatic
      disposition of HSA-coated NS-50 was much less than that of NS-50 in the presence
      of serum in the perfusate. To unravel the mechanism behind the less affinity of
      HSA-coated NS-50 to the liver, serum proteins associated on the surface was
      quantitatively and qualitatively assessed. The results indicated that pre-coated
      HSA impaired subsequent association of serum proteins onto the surface,
      suggesting that the association of a given serum protein with opsonic activity
      might be suppressed by HSA pre-coating. From these findings, pre-coating of
      nanoparticles with serum albumin could be useful to prevent their rapid clearance
      by mononuclear phagocyte system in vivo.

PMID- 15567510
TI  - Effects of repeated inhalation of toluene on ionotropic GABA A and glutamate
      receptor subunit levels in rat brain.
AB  - Toluene is a commonly abused solvent found in many industrial and commercial
      products. The neurobiological effects of toluene remain unclear, but many of
      them, like those of ethanol, may be mediated by gamma-aminobutyric acid (GABA)
      and glutamate receptors. Chronic ethanol administration has been shown to alter
      levels of specific subunits for GABA type A (GABA(A)), N-methyl-d-aspartate
      (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      receptors. However, little is known about the effects of toluene on subunit
      levels of these receptors. To examine this, rats were exposed to toluene vapors
      (8000 ppm) or air for 10 days (30 min/day), and afterwards GABA(A) alpha1, NR1
      and NR2B (NMDA) and GluR1 and GluR2/3 (AMPA) receptor subunit levels were
      determined in discrete brain regions of these animals by Western blotting.
      Toluene increased GABA(A) alpha1, NR1, NR2B and GluR2/3 subunits in the medial
      prefrontal cortex and decreased GABA(A) alpha1 and NR1 subunits in the substantia
      nigra compacta. Toluene inhalation produced modest increases in GABA(A) alpha1
      subunits in the striatum, as well as slight decreases in this subunit in the
      ventral tegmental area. NR2B subunit levels were also slightly increased within
      the nucleus accumbens by toluene. These studies show that toluene differentially
      alters the levels of specific GABAergic and glutamatergic receptor subunits in a
      regionally selective manner.

PMID- 15567511
TI  - Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal
      degeneration in Parkinson's disease and Huntington's disease.
AB  - Double-strand RNA dependent protein kinase (PKR) plays an important role in
      control of cell death. We previously reported that activation of PKR is
      associated with hippocampal neuronal loss in Alzheimer's disease (AD). Recent
      studies have reported that Parkinson's (PD) and Huntington's (HD) disease brains
      displayed progressive hippocampal neuronal loss in extrastriatal degeneration.
      However, association between PKR and hippocampal neuronal loss in PD and HD
      brains is not known. In this report, brain tissues from patients with PD and HD
      displayed strong induction of phosphorylated-PKR (p-PKR) in hippocampal neurons.
      Immunoblotting analysis also demonstrated that levels of nuclear p-PKR in the
      hippocampus affected by these diseases were increased compared with age-matched
      disease controls. These results suggest that a close association exists between
      PKR and extrastriatal degeneration in PD and HD pathology.

PMID- 15567512
TI  - Cerebellar protein expression in three different mouse strains and their
      relevance for motor performance.
AB  - The present study uses a proteomic approach to link motor function to cerebellar
      protein expression in 129X1/SvJ, C57BL/6J and nNOS WT mice. Poor performance on
      the Rota rod, the standard test for motor coordination, was detected in 129X1/SvJ
      mice. No gross impairments of neurological, cognitive and behavioural functions
      were observed. Identification and quantification of 48 proteins revealed reduced
      expression of calbindin, septin 5 and syntaxin binding protein 1 in 129X1/SvJ. In
      nNos WT glucose-6-phosphate 1 dehydrogenase X was decreased whereas
      dihydropyrimidinase-related protein-4 was increased. In C57BL/6J stress-70
      protein, alpha enolase, NAD-dependent deacetylase sirtuin 2, septin 2,
      dihydropyrimidinase-related protein-2 and brain derived neurotrophic factor
      showed elevated levels. Neurological examination, Rota rod test, Morris Water
      Maze, Multiple-T-Maze, Open field and Elevated plus-maze were employed to study
      motor, cognitive and behavioural function. Mice were sacrificed and cerebellar
      tissue was homogenized. Proteins were extracted and separated on two-dimensional
      gel electrophoresis with subsequent in-gel digestion followed by mass
      spectrometrical analysis of peptides (MALDI-TOF/TOF-TOF). Quantification of spots
      was carried out by specific software. A strong association of impaired motor
      function with altered cerebellar protein expression of calbindin, septin 5 and
      syntaxin binding protein 1in 129X1/SvJ was observed and is in agreement with
      previous observations of motor deficiencies in a calbindin knock-out mouse. These
      results have to be taken into account when using 129X1/SvJ for biochemical,
      toxicological or gene targeting experiments as well as when studying the above
      mentioned proteins or corresponding pathways and cascades in this mouse strain.

PMID- 15567513
TI  - Effects of positive AMPA receptor modulators on calpain-mediated spectrin
      degradation in cultured hippocampal slices.
AB  - Positive modulators of AMPA receptors (AMPAr), also known as ampakines, are
      allosteric effectors of the receptors and have been extensively studied in past
      years due to their potential use as treatment for various diseases and ailments
      of the central nervous system such as mild cognitive impairment, schizophrenia,
      and Alzheimer's disease. Ampakines have been shown to improve performance on
      memory tasks in animals and in human subjects, an effect linked to their ability
      to increase agonist-mediated ion influx through AMPAr, thus leading to enhanced
      synaptic responses and facilitation of long-term potentiation (LTP) induction at
      glutamatergic synapses. As LTP is associated with calpain activation and spectrin
      degradation, we determined the effects of ampakine treatment of cultured
      hippocampal slices on spectrin degradation. Calpain activation was evaluated by
      determining the levels of the 145-150kDa degradation products of spectrin. Our
      data indicated that incubation of hippocampal slices with some, but not all
      positive modulators of AMPA receptors resulted in enhanced spectrin degradation,
      an effect that was blocked by a calpain inhibitor. In addition, an antagonist of
      AMPAr but not of NMDAr blocked ampakine-induced spectrin degradation. These
      results indicate that prolonged treatment with selected ampakines leads to
      spectrin degradation mediated by activation of the calcium-dependent protease
      calpain.

PMID- 15567514
TI  - Regulation of XIAP and Smac/DIABLO in the rat hippocampus following transient
      forebrain ischemia.
AB  - We investigated the expression of XIAP (X chromosome-linked inhibitor of
      apoptosis protein) and Smac/DIABLO, a newly identified mitochondrial apoptogenig
      molecule in the hippocampus following transient global ischemia. Transient global
      ischemia produced by two-vessel occlusion triggers the delayed neuronal death of
      CA1 neurons in the hippocampus. We demonstrate that CA1 neuronal loss induced by
      ischemia (10 min) is preceded by a selective and marked elevation of
      catalytically active caspase-3 in these neurons, indicative of apoptosis. XIAP (X
      chromosome-linked inhibitor of apoptosis protein) is a member of the inhibitor of
      apoptosis (IAP) gene family that, in addition to suppressing cell death by
      inhibition of caspases, is involved in an increasing number of signalling
      cascades. The present study shows alterations in the levels of XIAP and of
      Smac/DIABLO (second mitochondrial activator of caspase) after cerebral ischemia.
      The protein levels of XIAP and the number of XIAP-positive cells were regulated
      by cerebral ischemia in a strictly time and region dependent manner. The largest
      change in XIAP-IR was observed in the CA1 sub field, which is the most vulnerable
      area of hippocampus. The mitochondrial expression level of Smac/DIABLO increased
      during reperfusion. Smac/DIABLO expression was associated with alteration of the
      XIAP levels and the appearance of activated form of caspase-3 within the
      hippocampus during reperfusion in spatial and temporal manners.

PMID- 15567515
TI  - Omega-agatoxin-TK is a useful tool to study P-type Ca2+ channel-mediated changes
      in internal Ca2+ and glutamate release in depolarised brain nerve terminals.
AB  - The present study shows that omega-agatoxin-TK, a toxin of the venom of
      Agelenopsis aperta, which is 10 times more concentrated than the P/Q type Ca(2+)
      channel blocker, omega-agatoxin-IVA in the venom, inhibits the high K(+)
      depolarisation-induced rise in internal Ca(2+) (Ca(i), as determined with fura-2)
      dose dependently in cerebral (striatal and hippocampal) isolated nerve endings,
      with calculated IC(50)'s of about 60nM. The maximal inhibition exerted by omega
      agatoxin-TK in striatal synaptosomes (61 +/- 11%) is 10% larger than in
      hippocampal synaptosomes, suggesting a larger population of omega-agatoxin-TK
      sensitive Ca(2+) channels in striatal than in hippocampal nerve endings. The N
      type Ca(2+) channel blocker, omega-conotoxin-GVIA (1muM), inhibits part of the
      omega-agatoxin-TK-insensitive rise in Ca(i) induced by high K(+). In contrast to
      the inhibition exerted by omega-agatoxin-TK on the Ca(i) response to high K(+),
      omega-agatoxin-TK failed to inhibit the tetrodotoxin-sensitive elevations in
      Ca(i) and in internal Na(+) (Na(i), as determined with SBFI) induced by
      veratridine, indicating that the Ca(2+) influx activated by veratridine does not
      involve omega-agatoxin-TK-sensitive channels. High K(+) does not increase Na(i).
      In [(3)H]Glu preloaded hippocampal synaptosomes super-fused with low Na(+) Krebs
      Ringer HEPES (a condition that guarantees the elimination of neurotransmitter
      transporters-mediated release), the release of [(3)H]Glu induced by high K(+) is
      absolutely dependent on the entrance of external Ca(2+). This exocytotic release
      of [(3)H]Glu attained in the absence of a chemical Na(+) gradient is inhibited
      with the same potency and efficacy by omega-agatoxin-TK and by omega-agatoxin
      IVA, which is known to differ from omega-agatoxin-TK in its amino terminal
      moiety. These results indicate that omega-agatoxin-TK represents a good
      pharmacological tool to study P/Q type Ca(2+) channel-mediated responses in
      cerebral nerve endings.

PMID- 15567516
TI  - Neurotrophins protect against cytosine arabinoside-induced apoptosis of immature
      rat cerebellar neurons.
AB  - Neurotrophin-induced neuroprotection against apoptosis was investigated using
      immature cultured cerebellar granule cells (CGC) from newborn rat pups. Apoptotic
      cell death induced by treatment with cytosine arabinoside (AraC) was confirmed by
      DNA fragmentation and quantified by cell survival assays. AraC was most effective
      in inducing apoptosis when added to CGC on the day of culture preparation, while
      less or no effect was observed when added at 24 or 48h after plating,
      respectively. Pretreatment of CGC cultures for 24h with brain-derived
      neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), but not neurotrophin-3 (NT
      3), robustly protected against AraC neurotoxicity. K252a, an inhibitor of the
      tropomyosin-related kinase (Trk) tyrosine kinase receptor family which showed no
      toxicity by itself, blocked BDNF protection of AraC-induced apoptosis in a
      concentration-dependent manner. Neither protein kinase C activation nor
      inhibition mimicked or affected BDNF protection against AraC neurotoxicity. BDNF,
      but not NT-3, treatment of immature CGC caused a marked, but transient activation
      of Akt through phosphatidylinositol (PI) 3-kinase. The neuroprotective effects of
      BDNF were suppressed by pretreatment with LY 294002 (a PI 3-kinase inhibitor).
      BDNF neuroprotection was also preceded by activation of mitogen activated protein
      kinase (MAPK) and suppressed by two MAPK/ERK (MEK)-selective inhibitors, PD 98059
      and U-0126. Moreover, inhibitors of PI 3-kinase and MEK potentiated AraC-induced
      neurotoxicity. These results show that neurotrophins protect against AraC-induced
      apoptosis, at least in part, through TrkB-mediated activation of the PI 3
      kinase/Akt and MEK signaling pathways.

PMID- 15567517
TI  - Role of Bcl-2 family of proteins in mediating apoptotic death of PC12 cells
      exposed to oxygen and glucose deprivation.
AB  - Apoptotic cell death has been observed in many in vivo and in vitro models of
      ischemia. However, the molecular pathways involved in ischemia-induced apoptosis
      remain unclear. We have examined the role of Bcl-2 family of proteins in
      mediating apoptosis of PC12 cells exposed to the conditions of oxygen and glucose
      deprivation (OGD) or OGD followed by restoration of oxygen and glucose (OGD
      restoration, OGD-R). OGD decreased mitochondrial membrane potential and induced
      necrosis of PC12 cells, which were both prevented by the overexpression of Bcl-2
      proteins. OGD-R caused apoptotic cell death, induced cytochrome C release from
      mitochondria and caspase-3 activation, decreased mitochondrial membrane
      potential, and increased levels of pro-apoptotic Bax translocated to the
      mitochondrial membrane, all of which were reversed by overexpression of Bcl-2.
      These results demonstrate that the cell death induced by OGD and OGD-R in PC12
      cells is potentially mediated through the regulation of mitochondrial membrane
      potential by the Bcl-2 family of proteins. It also reveals the importance of
      developing therapeutic strategies for maintaining the mitochondrial membrane
      potential as a possible way of reducing necrotic and apoptotic cell death that
      occurs following an ischemic insult.

PMID- 15567518
TI  - PC12 and HEL cell communication in a reconstituted synapse analyzed with
      mathematical modeling.
AB  - A synapse simulating model comprising of the nerve growth factor (NGF)
      differentiated PC12 cells releasing neurotransmitter (NT) and sensor 92.1.7.human
      erythroleukemia (HEL) cells has been used for simulating the connection between
      neurons and target cells. A Ca(2+) elevation was observed in both cell types when
      the PC12 cells were challenged with nicotine. The response patterns of individual
      cell were subsequently analyzed mathematically. The Ca(2+) signals of the PC12
      cells were described by an equation representing a simple bi-exponential
      function. The NT-noradrenaline discharged by the PC12 cells in response to
      nicotine caused heterogeneous secondary Ca(2+) elevations in the HEL cells after
      a certain delay. Model fitting of this response disclosed slow "hidden"
      oscillations and heterogeneous secondary Ca(2+) signals could be grouped on the
      basis of the oscillation frequency. As determined in control experiments with
      noradrenaline (NA), the value of oscillation frequency also revealed a good
      correlation with the NT concentration.

PMID- 15567519
TI  - Scientiae forum / models and speculations pathways for axonal targeting of
      membrane proteins.
AB  - The distribution of proteins to the correct domains of neurons is crucial for
      neuronal functioning. Here I discuss possible mechanisms underlying sorting to
      the axonal plasma membrane which differ with respect to the steps providing
      selectivity for axonal vs. somatodendritic cargo. Selectivity can be executed at
      one or more than one step, including sorting into distinct carriers in the Golgi,
      preferential transport along axonal microtubules, fusion with the plasma
      membrane, and importantly retrieval by endocytosis. A protein might in fact be
      sorted multiple times at different places to achieve axonal localization.

PMID- 15567520
TI  - Can the description of a cascade of biochemical events establish the basis of the
      integration of a biological function?

PMID- 15567521
TI  - A cascade of biochemical events creates emergence.

PMID- 15567522
TI  - Testing the geometric clutch hypothesis.
AB  - The Geometric Clutch hypothesis is based on the premise that transverse forces (t
      forces) acting on the outer doublets of the eukaryotic axoneme coordinate the
      action of the dynein motors to produce flagellar and ciliary beating. T-forces
      result from tension and compression on the outer doublets when a bend is present
      on the flagellum or cilium. The t-force acts to pry the doublets apart in an
      active bend, and push the doublets together when the flagellum is passively bent
      and thus could engage and disengage the dynein motors. Computed simulations of
      this working mechanism have reproduced the beating pattern of simple cilia and
      flagella, and of mammalian sperm. Cilia-like beating, with a clearly defined
      effective and recovery stroke, can be generated using one uniformly applied
      switching algorithm. When the mechanical properties and dimensions appropriate to
      a specific flagellum are incorporated into the model the same algorithm can
      simulate a sea urchin or bull sperm-like beat. The computed model reproduces many
      of the observed behaviors of real flagella and cilia. The model can duplicate the
      results of outer arm extraction experiments in cilia and predicted two types of
      arrest behavior that were verified experimentally in bull sperm. It also
      successfully predicted the experimentally determined nexin elasticity.
      Calculations based on live and reactivated sea urchin and bull sperm yielded a
      value of 0.5 nN/microm for the t-force at the switch-point. This is a force
      sufficient to overcome the shearing force generated by all the dyneins on one
      micron of outer doublet. A t-force of this magnitude should produce substantial
      distortion of the axoneme at the switch-point, especially in spoke or spoke-head
      deficient motile flagella. This concrete and verifiable prediction is within the
      grasp of recent advances in imaging technology, specifically cryoelectron
      microscopy and atomic force microscopy.

PMID- 15567523
TI  - Speculations on the evolution of 9+2 organelles and the role of central pair
      microtubules.
AB  - Motility generated by 9+2 organelles, variably called cilia or flagella, evolved
      before divergence from the last common ancestor of extant eukaryotes. In order to
      understand better how motility in these organelles is regulated, evolutionary
      steps that led to the present 9+2 morphology are considered. In addition, recent
      advances in our knowledge of flagellar assembly, together with heightened
      appreciation of the widespread role of cilia in sensory processes, suggest that
      these organelles may have served multiple roles in early eukaryotic cells. In
      addition to their function as undulating motility organelles, we speculate that
      protocilia were the primary determinants of cell polarity and directed motility
      in early eukaryotes, and that they provided the first defined membrane domain for
      localization of receptors that allowed cells to respond tactically to
      environmental cues. Initially, motility associated with these protocilia may have
      been gliding motility rather than the more complex bend propagation. Once these
      protocilia became functional motile organelles for beating, we believe that
      addition of an asymmetric central apparatus, capable of transducing signals to
      dynein motors and altering beat parameters, provided refined directional control
      in response to tactic signals. This paper presents hypothesized steps in this
      evolutionary process, and examples to support these hypotheses.

PMID- 15567524
TI  - Oscillation modes of microtubules.
AB  - Microtubules are long, filamentous protein complexes which play a central role in
      several cellular physiological processes, such as cell division transport and
      locomotion. Their mechanical properties are extremely important since they
      determine the biological function. In a recently published experiment [Phys. Rev.
      Lett. 89 (2002) 248101], microtubule's Young's and shear moduli were
      simultaneously measured, proving that they are highly anisotropic. Together with
      the known structure, this finding opens the way to better understand and predict
      their mechanical behavior under a particular set of conditions. In the present
      study, we modeled microtubules by using the finite elements method and analyzed
      their oscillation modes. The analysis revealed that oscillation modes involving a
      change in the diameter of the microtubules strongly depend on the shear modulus.
      In these modes, the correlation times of the movements are just slightly shorter
      than diffusion times of free molecules surrounding the microtubule. It could be
      therefore speculated that the matching of the two timescales could play a role in
      facilitating the interactions between microtubules and MT associated proteins,
      and between microtubules and tubulins themselves.

PMID- 15567525
TI  - TPPP/p25: from unfolded protein to misfolding disease: prediction and
      experiments.
AB  - TPPP/p25, the first representative of a new protein family, identified as a brain
      specific unfolded protein induces aberrant microtubule assemblies in vitro,
      suppresses mitosis in Drosophila embryo and is accumulated in inclusion bodies of
      human pathological brain tissues. In this paper, we present prediction and
      additional experimental data that validate TPPP/p25 to be a new member of the
      "intrinsically unstructured" protein family. The comparison of these
      characteristics with that of alpha-synuclein and tau, involved also in
      neurodegenerative diseases, suggested that although the primary sequences of
      these proteins are entirely different, there are similarities in their well
      defined unstructured segments interrupted by "stabilization centres",
      phosphorylation and tubulin binding motives. SK-N-MC neuroblastoma cells were
      transfected with pEGFP-TPPP/p25 construct and a stable clone denoted K4 was
      selected and used to establish the effect of this unstructured protein on the
      energy state/metabolism of the cells. Our data by analyzing the mitochondrial
      membrane polarization by fluorescence microscopy revealed that the high-energy
      phosphate production in K4 clone is not damaged by the TPPP/p25 expression.
      Biochemical analysis with cell homogenates provided quantitative data that the
      ATP level increased 1.5-fold and the activities of hexokinase, glucosephosphate
      isomerase, phosphofructokinase, triosephosphate isomerase and glyceraldehyde-3
      phosphate dehydrogenase were 1.2 to 2.0-fold higher in K4 as compared to the
      control. Our modelling using these data and rate equations of the individual
      enzymes suggests that the TPPP/p25 expression stimulates glucose metabolism. At
      pathological conditions TPPP/p25 is localized in inclusion bodies in multiple
      system atrophy, it tightly co-localizes with alpha-synuclein, partially with
      tubulin and not with vimentin. The previous and the present studies obtained with
      immunohistochemistry with pathological human brain tissues rendered it possible
      to classify among pathological inclusions on the basis of immunolabelling of
      TPPP/p25, and suggest this protein to be a potential linkage between Parkinson's
      and Alzheimer's diseases.

PMID- 15567526
TI  - Understanding the parts in terms of the whole.
AB  - Metabolism is usually treated as a set of chemical reactions catalysed by
      separate enzymes. However, various complications, such as transport of molecules
      across membranes, physical association of different enzymes, giving the
      possibility of metabolite channelling, need to be taken into account. More
      generally, a proper understanding of the nature of life will require metabolism
      to be treated as a complete system, and not just as a collection of components.
      Certain properties of metabolic systems, such as feedback inhibition of the first
      committed step of a pathway, make sense only if one takes a broader view of a
      pathway than is usual in textbooks, so that one can appreciate ideas such as
      regulation of biosynthesis according to demand. More generally still,
      consideration of metabolism as a whole puts the emphasis on certain systemic
      aspects that are crucial but which can pass unnoticed if attention is always
      focussed on details. For example, a living organism, unlike any machine known or
      conceivable at present, makes and maintains itself and all of its components. Any
      serious investigation of how this can be possible implies an infinite regress in
      which each set of enzymes needed for the metabolic activity of the organism
      implies the existence of another set of enzymes to maintain them, which, in turn,
      implies another set, and so on indefinitely. Avoiding this implication of
      infinite regress represents a major challenge for future investigation.

PMID- 15567527
TI  - Reduction, integration and emergence in biochemical networks.
AB  - Most studies of molecular cell biology are based upon a process of decomposition
      of complex biological systems into their components, followed by the study of
      these components. The aim of the present paper is to discuss, on a physical
      basis, the internal logic of this process of reduction. The analysis is performed
      on simple biological systems, namely protein and metabolic networks. A multi
      sited protein that binds two ligands x and y can be considered the simplest
      possible biochemical network. The organization of this network can be described
      through a comparison of three systems, i.e. XY, X and Y. X and Y are component
      sub-systems that collect states x(i) and y(j), respectively, i.e. protein states
      that have bound either i molecules of x (whether or not these states have also
      bound y), or j molecules of y (whether or not these states have bound x). XY is a
      system made up of the specific association of X and Y that collects states
      x(i)y(j). One can define mean self-informations per node of the network, <H(X)>,
      <H(Y)> and <H(X,Y)>. Reduction of the system XY into its components is possible
      if, and only if, <H(X,Y)>,is equal to the sum of <H(X)> and <H(Y)>. If <H(X,Y)>
      is smaller than the sum of<H(X)> and <H(Y)>, the system is integrated, for it has
      less self-information than the set of its components X and Y. It can also occur
      that <H(X,Y)>, be larger than the sum of <H(X)> and <H(Y)>. Hence, the system XY
      displays negative integration and emergence of self-information relative to its
      components X and Y. Such a system is defined as complex. Positive or negative
      integration of the system implies it cannot be reduced to its components. The
      degree of integration can be measured by a function <I(X:Y)>, called mutual
      information of integration. In the case of enzyme networks, emergence of self
      information is associated with emergence of catalytic activity. Moreover, if the
      enzyme reaction is part of a metabolic sequence, its mutual information of
      integration can be increased by an effect of context of this sequence.

PMID- 15567528
TI  - Glial fibrillary acidic protein (GFAP)-like immunoreactivity in the visual system
      of the crab Ucides cordatus (Crustacea, Decapoda).
AB  - Glial fibrillary acidic protein (GFAP) is the main intermediate filament protein
      used as a marker for the identification of astrocytes in the central nervous
      system of vertebrates. Analogous filaments have been observed in the glial cells
      of many mollusks and annelids but not in crustaceans. The present study was
      carried out to identify by light microscopy immunohistochemistry,
      immunoelectronmicroscopy and immunoblotting, GFAP-like positive structures in the
      visual system of the crab Ucides cordatus as additional information to help
      detect and classify glial cells in crustaceans. Conventional electron microscopy,
      light microscopy of semithin sections and fluorescence light microscopy were also
      employed to characterize cells and tissues morphology. Our results indicated the
      presence of GFAP-like positive cell processes and cell bodies in the retina and
      adjoining optic lobe. The labeling pattern on the reactive profiles was
      continuous and very well defined, differing considerably from what has been
      previously reported in the central nervous system of some mollusks, where a
      diffuse spotted fluorescence pattern of labeling was observed. We suggest that
      this glial filament protein may be conserved in the evolution of the invertebrate
      nervous systems and that it may be used as a label for some types of glial cells
      in the crab.

PMID- 15567529
TI  - The median body of Giardia lamblia: an ultrastructural study.
AB  - Giardia lamblia is an intestinal parasite of several mammals. The most striking
      feature of Giardia is the presence of a complex and unique cytoskeleton, and
      among its components the median body (MB) is the least defined microtubular
      structure. In the present study, we used a technique that allowed the removal of
      the plasma membrane and observation of cytoskeletal structures by both routine
      scanning electron microscopy (SEM) and field emission high resolution SEM. This
      technique permitted new observations such as details and insights of the median
      bodies, not previously described or controversial in the literature. Light
      microscopy after Panotic staining, immunofluorescence microscopy using several
      antibodies, and thin sections were also used to better characterized the Giardia
      MB. The new observations concerning the median bodies were : (1) they are not one
      or two structures, but varied in number, shape and position ; (2) they were found
      in mitotic and interphasic trophozoites, in disagreement with previous works ;
      (3) they were present in about 80 % of the cells, and not in 50 % of the cells,
      as previously described ; (4) they could be connected either to the plasma
      membrane, to the adhesive disc, and caudal flagella, and thus they are not
      completely free in the cells, as published before ; (5) they can protrude the
      cell surface ; (6) their microtubules react with several anti-tubulin and -beta
      giardin antibodies. These observations add new data on the scarce literature and
      to this largely understudied cell structure.

PMID- 15567530
TI  - Autolabeling 3D tracks using neural networks.
AB  - Motion capturing systems based on monochrome video have problems assigning
      measured 3D marker positions to the anatomically defined positions or labels of
      the markers applied to the test subject. This task is usually called "labelling"
      and is paramount to the reconstruction of 3D trajectories from a set of video
      frames from multiple cameras--the tracking procedure. Labelling means sorting a
      set of 3D vectors by their spatial positions. Neural networks can be made to
      "learn" from examples of marker positions in a given marker set, i.e. previously
      manually tracked video sequences. Trained neural networks are able to calculate a
      set of sorted approximate marker positions from an unsorted set of exact marker
      positions. The set of sorted exact positions can be found by pairing up both sets
      of marker positions via a minimum distance function. The neural network is
      trained only once and can then be applied to any number of individuals. The
      algorithm is designed for cyclic motions like for locomotion analysis.

PMID- 15567531
TI  - Relationships of EMG to effort in the trunk under isometric conditions: force
      increasing and decreasing effects and temporal delays.
AB  - BACKGROUND: Electromyograms are used in increasingly sophisticated biomechanical
      analyses to estimate forces within the trunk to prevent and evaluate painful
      spinal conditions. However, even under nominally isometric conditions the
      relationship between EMG and effort is complex. This study quantified influences
      of pulling direction, increasing versus decreasing effort and electromechanical
      delay on the EMG/effort relationships for principal lower trunk muscle groups in
      isometric pulling tasks, to determine whether the observed differences between
      increasing versus decreasing effort relationships were consistent with
      electromechanical delay or activation differences. METHODS: Twenty-three healthy
      subjects (15 male, 8 female; mean age 32 years; mean bodymass 74.5 kg) each stood
      in an apparatus to stabilize the pelvis and performed ramped isometric efforts
      with a harness around the thorax connected to each of a series of five anchor
      points on the wall, for angles of pull at each 45 degrees increment from 0
      degrees to 180 degrees to the anterior direction. A load cell recorded the
      generated force for a 5 s timed increase up to a voluntary maximum, a 1s 'dwell',
      and a 5 s relaxation back to zero effort. EMG signals were recorded via
      electrodes (surface, except indwelling for multifidus) from right and left rectus
      abdominis, internal and external obliques, longissimus, iliocostalis and L2 and
      L4 level multifidus. EMG signals were rectified with a 250 ms root-mean-square
      moving average filter. Effort-increasing and effort-decreasing sections of
      recordings were analyzed separately. FINDINGS: The EMG/effort relationship had a
      statistically significantly greater gradient as the effort was increasing than
      when decreasing for 28 of 70 muscle-angle permutations. This difference in
      gradient was found to explain a significant part of the apparent lag between
      effort generated and EMG signal that averaged between 261 and 658 ms before and
      between 31 and 196 ms for different muscles after the slope difference was taken
      into account. INTERPRETATION: The findings were consistent with the notion that
      the motor unit recruitment differs in increasing versus decreasing isometric
      efforts, probably because of a small stretching of the muscle as its tension
      increases. The residual temporal delay was thought to represent electromechanical
      delay.

PMID- 15567532
TI  - Effects of static flexion-relaxation on paraspinal reflex behavior.
AB  - BACKGROUND: Static trunk flexion working postures and disturbed trunk muscle
      reflexes are related to increased risk of low-back pain. Animal studies conclude
      that these factors may be related; passive tissue strain in spinal ligaments
      causes subsequent short-term changes in reflex. Although studies have documented
      changes in the myoelectric onset angle of flexion-relaxation following prolonged
      static flexion and cyclic flexion we could find no published evidence related to
      the human reflex response of the trunk extensor muscles following a period of
      static flexion-relaxation loading. METHODS: Eighteen subjects maintained static
      lumbar flexion for 15 min. Paraspinal muscle reflexes were elicited both before
      and after the flexion-relaxation protocol using pseudorandom stochastic force
      disturbances while recording EMG. Reflex gain was computed from the peak value of
      the impulse response function relating input force perturbation to EMG response
      using time-domain deconvolution analyses. FINDINGS: Reflexes showed a trend
      toward increased gain after the period of flexion-relaxation (P < 0.055) and were
      increased with trunk extension exertion (P < 0.021). Significant gender
      differences in reflex gain were observed (P < 0.01). INTERPRETATIONS:
      Occupational activities requiring extended periods of trunk flexion contribute to
      changes in reflex behavior of the paraspinal muscles. Results suggest potential
      mechanisms by which flexed posture work may contribute to low-back pain.
      Significant gender differences indicate risk analyses should consider personal
      factors when considering neuromuscular behavior.

PMID- 15567533
TI  - The effect on anterior column loading due to different vertebral augmentation
      techniques.
AB  - BACKGROUND: Vertebral compression fractures are a significant cause of morbidity
      amongst the elderly, resulting in pain, kyphosis, decreased mobility, and often
      depression. The two most popular operative treatments of compression wedge
      fractures are vertebroplasty and kyphoplasty, however, which method leads to
      restoration of normal spinal loading is unknown. METHODS: A cadaveric
      thoracolumbar spine model was fractured and then treated using one of two
      techniques: vertebroplasty or kyphoplasty. Three non-destructive loading regimes
      were applied to the intact, fractured and treated cases. Sub-adjacent nuclear
      pressure, used as a measure of anterior column loading, was determined for each
      experimental variant and loading case. FINDINGS: The data indicate that nuclear
      pressure was substantially reduced after the spine was fractured. These pressures
      were minimally increased after treatment, however, not to the level of the pre
      fractured condition. In all loading cases, there were no significant differences
      between the two treatment types. INTERPRETATION: While our data show that both
      vertebroplasty and kyphoplasty allow the disc to generate higher nuclear
      pressures, neither treatment increased nucleus pulposus pressure above the level
      of the intact state. This directly relates to the clinical condition in that
      adjacent segment fractures sustained subsequent to either treatment is likely the
      result of overall disease progression, and not a direct result of the
      intervention.

PMID- 15567534
TI  - Scapular kinematics during transfers in manual wheelchair users with and without
      shoulder impingement.
AB  - BACKGROUND: Scapular function during humeral elevation has been reported in
      groups with and without shoulder impingement pathology. To date, no one has
      assessed scapular kinematics during upper extremity loaded tasks that manual
      wheelchair users must perform on a daily basis. Therefore, the objective of this
      study was to compare scapular kinematics and muscle activation patterns during
      two different wheelchair transfers in groups of manual wheelchair users with and
      without shoulder impingement. METHODS: A case controlled study of manual
      wheelchair users, with and without shoulder impingement was performed. Twenty
      three male manual wheelchair users (13 without shoulder impingement, 10 with
      shoulder impingement) performed transfers toward the involved or dominant limb
      (lead limb transfer) and away from the instrumented limb (trail limb transfer).
      Position and orientation measures of the thorax, scapula and humerus were
      obtained using an electromagnetic tracking system. Muscle activity data were
      collected using telemetered electromyography. Each subject performed three trials
      of wheelchair transfers to each side. FINDINGS: Manual wheelchair users with
      impingement performed transfers with reduced thoracic flexion, increased scapular
      internal rotation, and increased humeral internal rotation as compared to those
      without impingement. Differences were found between the tasks in the scapular
      motions and EMG amplitude. Trail limb transfer presented with reduced scapular
      upward rotation and posterior tip as compared to the lead limb transfer task.
      Increased muscle activity for the lower trapezius and serratus anterior muscles
      was demonstrated in the trail limb transfer. INTERPRETATION: This study provides
      the first kinematic description of scapular kinematics during transfer tasks.
      Shoulder impingement and direction of transfer does affect transfer task
      performance in manual wheelchair users. Scapular kinematics and muscle patterns
      during transfers may predispose manual wheelchair users to the development of
      shoulder pathology.

PMID- 15567535
TI  - Anatomical and mechanical changes following repetitive eccentric exertions.
AB  - BACKGROUND: Submaximal eccentric exertions occur occupationally when rapidly
      rising tool-generated forces exceed the operator's capacity to react against
      them. The purpose of this study was to investigate the effects of short duration
      repetitive submaximal eccentric forearm exertions at levels comparable to
      industrial power hand tool use on dynamic mechanical properties (stiffness,
      effective mass and damping) and on forearm edema. METHODS: This study
      investigated changes following short term repetitive submaximal eccentric
      exertions comparable to occupational levels. Eight male participants exercised
      eccentrically for 30 min at 50% of isometric maximum voluntary contraction
      forearm supination in a posture and loading similar to power hand tool use in the
      workplace. Dynamic mechanical properties (stiffness, effective mass and damping)
      of the upper limb were measured before, immediately following, and daily for
      three days after the activity. An MRI scan to assess edema was also performed for
      five of the participants before, on day one and day three following the activity.
      FINDINGS: Mechanical stiffness decreased 51% (P < 0.05) and effective mass
      decreased 43% (P = 0.052) immediately following eccentric exercise. Average
      isometric strength also decreased 42% immediately following exercise (P < 0.01)
      and pain persisted for two days. The recovery of static strength however was not
      correlated with changes in mechanical stiffness (r = 0.56) or effective mass (r =
      0.30). The exercised arms had a 360% increase (P < 0.01) in supinator-extensor
      T(2) relaxation time difference, a quantifiable measure of edema, one day after
      exercise while the non-exercised arms had no significant changes. INTERPRETATION:
      Changes in both T(2) relaxation time, indicative of edema, and forearm mechanical
      properties, were observed following short duration submaximal repetitive
      exercise. If similar changes in dynamic mechanical properties of the upper
      extremity occur following repetitive submaximal eccentric activity in the
      workplace, they could negatively impact the ability of the arm to react to rapid
      forceful loading during repetitive industrial work activities and increase
      mechanical loading of the upper limb.

PMID- 15567536
TI  - Tendon and nerve displacement at the wrist during finger movements.
AB  - BACKGROUND: Repetitive motion of the hand has been suggested as a major factor of
      pathogenesis of cumulative trauma disorders (e.g., carpal tunnel syndrome). The
      purpose of this study was to investigate the 3D displacement of the median nerve
      and extrinsic finger flexor tendons (flexor digitorum superficialis; flexor
      digitorum profundus) as a function of flexion/extension of metacarpophalangeal
      joints of the index and middle fingers. METHODS: Shim markers were placed on the
      median nerve, flexor digitorum superficialis, and flexor digitorum profundus
      tendons at the wrist region of seven cadaveric specimens for the purpose of
      digitization of tendon and nerve locations. The metacarpophalangeal joint of the
      index or middle finger was moved from 15 degrees extension to 75 degrees of
      flexion while the markers were digitized at increments of 15 degrees. Marker
      displacements were determined in the longitudinal, radial-ulnar, and dorsal
      palmar directions. FINDINGS: Movement of metacarpophalangeal joint of the index
      or middle finger caused tendon and nerve displacements in the longitudinal,
      radial-ulnar, and dorsal-palmar directions. The longitudinal displacements of the
      median nerve and the flexor tendons were linearly correlated with angular
      movement of the metacarpophalangeal joint. The maximum longitudinal displacements
      of the flexor digitorum superficialis tendon, flexor digitorum profundus tendon,
      and median nerve were, on average, 14.7 mm, 11.9 mm, and 3.0 mm, respectively,
      for the index finger; and 18.4 mm, 14.5 mm, and 4.0 mm, respectively, for the
      middle finger. The radial-ulnar and dorsal-palmar displacements were irregular
      and relatively small. The maximum displacements in these transverse directions
      fell in the range of 1.4-5.1 mm for the median nerve and 1.9-7.3 mm for the
      flexor tendons. INTERPRETATIONS: Finger flexor tendons and median nerve move not
      only concurrently, but also differentially, in all anatomical directions. Tendon
      and nerve movement during prolonged repetitive hand movement may cause hand
      disorders such as carpal tunnel syndrome.

PMID- 15567537
TI  - Does the orientation of the distal radioulnar joint influence the force in the
      joint and the tension in the interosseous membrane?
AB  - OBJECTIVE: To investigate the effect of change in the orientation of the distal
      radioulnar joint on the force in the joint and the strain in the interosseous
      membrane. DESIGN: Biomechanical study in fresh frozen cadavers. BACKGROUND: The
      articular surfaces of the distal radioulnar joint may be orientated in parallel
      with the long axis of the forearm (a Type I joint) or at an oblique angle opening
      distally to the ulnar side (a Type II joint). METHODS: Three cadaveric upper
      limbs were held on a custom built frame allowing measured rotation and axial
      loading across the wrist. Measurements of force in the distal radioulnar joint
      and strain in the interosseous membrane were taken and repeated after replacement
      of the distal radioulnar joint with prosthetic Type I and Type II joints.
      FINDINGS: The force in the joint and the strain in the interosseous membrane
      increased with increasing load across the wrist (P < 0.0001). The force in the
      Type I joint was reduced compared to the normal or Type II joint. This difference
      was greater with increasing load and was significant at 8 kg (P < 0.001). The
      strain in the interosseous membrane was maximal at neutral forearm rotation and
      decreased with increasing pronation and supination. INTERPRETATION: The force in
      the joint is greater with the Type II distal radioulnar joint. We believe this
      compressive force increases joint stability and this orientation of the articular
      surfaces should be considered in the design of a total distal radioulnar joint
      arthroplasty.

PMID- 15567538
TI  - The degrees to which transtrochanteric rotational osteotomy moves the region of
      osteonecrotic femoral head out of the weight-bearing area as evaluated by
      computer simulation.
AB  - BACKGROUND: Transtrochanteric rotational osteotomy is a technical demanding
      procedure. Currently, the pre-operative planning of the transtrochanteric
      rotational osteotomy is mostly based on X-ray images. The surgeons would need to
      reconstruct the three-dimensional structure of the femoral head and the necrosis
      in their mind. This study develops a simulation platform using computer models
      based on the computed tomography images of the femoral head to evaluate the
      degree to which transtrochanteric rotational osteotomy moves the region of
      osteonecrotic femoral head out of the weight-bearing area in stance and gait
      cycle conditions. Based on this simulation procedure, the surgeons would be
      better informed before the surgery and the indication can be carefully assessed.
      METHOD: A case with osteonecrosis involving 15% of the femoral head was
      recruited. Virtual models with the same size lesion but at different locations
      were devised. Computer models were created using SolidWorks 2000 CAD software.
      The area ratio of weight-bearing zone occupied by the necrotic lesion on two
      conditions, stance and gait cycle, were measured after surgery simulations.
      FINDINGS: For the specific case and virtual models devised in this study,
      computer simulation showed the following two findings: (1) The degrees needed to
      move the necrosis out of the weight-bearing zone in stance were less by anterior
      rotational osteotomy as compared to that of posterior rotational osteotomy.
      However, the necrotic region would still overlap with the weight-bearing area
      during gait cycle. (2) Because the degrees allowed for posterior rotation were
      less restricted than anterior rotation, posterior rotational osteotomies were
      often more effective to move the necrotic region out of the weight-bearing area
      during gait cycle. INTERPRETATION: The computer simulation platform by
      registering actual CT images is a useful tool to assess the direction and degrees
      needed for transtrochanteric rotational osteotomy. Although the results indicated
      that anterior rotational osteotomy was more effective to move the necrosis out of
      the weight-bearing zone in stance for models devised in this study, in
      circumstances where the necrotic region located at various locale, considering
      the limitation of anterior rotation inherited with the risk of vascular
      compromise, it might be more beneficial to perform posterior rotation osteotomy
      in taking account of gait cycle.

PMID- 15567539
TI  - A biomechanical study comparing cortical onlay allograft struts and plates in the
      treatment of periprosthetic femoral fractures.
AB  - BACKGROUND: Periprosthetic femoral fractures with well-fixed femoral components
      can be difficult to manage and internal fixation is usually necessary. This study
      was designed to determine the effect of cable plate, strut allograft and combined
      plate and strut allograft fixations of periprosthetic femoral fractures. METHODS:
      A transverse fracture at the level of the tip of the femoral stem was simulated
      in six cadaveric femurs. The fracture was fixed with a plate-strut graft
      construct with and without proximal screws, a plate only construct with and
      without proximal screws and with both anterior and lateral struts grafts of 12 cm
      or 20 cm in length. The intact femur and the six constructs were tested using
      anteroposterior and axial loads to simulate the forces at the hip during gait.
      The interfragmentary motions were measured with an optoelectronic camera system.
      FINDINGS: The highest median interfragmentary translations were observed with the
      plate only construct without proximal screws. No significant differences in
      median translations were found between the combined plate-strut and the strut
      graft alone constructs. Median interfragmentary rotations were largest with the
      plate only construct and lowest with the plate-strut constructs. INTERPRETATION:
      The best fracture fixation was achieved with the combined plate and strut graft
      constructs particularly in combination with the two unicortical screws above the
      fracture. The plate only constructs may not provide sufficient fixation stability
      in rotation for the simulated transverse fracture. The within-construct
      interfragmentary motions were not significantly different except for the plate
      only constructs. This suggests that the fixation construct type is the
      determining factor of interfragmentary motion.

PMID- 15567540
TI  - Importance of pre-clinical testing exemplified by femoral fractures in vitro with
      new bone preparation technique.
AB  - BACKGROUND: A new bone preparation technique, using smooth tamps for bone
      compaction, has increased crucial initial implant stability. However, preparing
      the femur with bulky smooth tamps, which from size to size increases the same
      amount in anterior to posterior as in lateral to medial dimensions, has increased
      the risk of a femoral fracture. This study examined whether compaction also
      involved an increased femoral fracture risk when using newly developed smooth
      tamps with a slim anterior to posterior dimension. METHODS: One femur in each
      pair of 10 cadaver femurs was prepared by the compaction technique using
      cylindrical reamers and smooth tamps. The contralateral femur was conventionally
      prepared with conical reamers and toothed rasps. The tamps and rasps differed in
      design as a proximal lateral tip was only present on the smooth tamps. Using a
      standardized test protocol, the instruments were driven into the femoral canal in
      controlled manner by a drop tower. FINDINGS: At maximum test conditions, five of
      10 femurs in the compaction group had fractured, as compared with no fractures in
      the rasping group. All fractures were longitudinal fissures in the greater
      trochanter, and these fissures were associated with the extended proximal lateral
      tip of the tamps. INTERPRETATION: Since the lateral fractures in the compaction
      group were associated with the extended proximal lateral tip of the tamps, it
      seems that fracture rates are influenced by instrumentation design. Therefore
      adequate pre-clinical evaluation is warranted prior to the introduction of new
      implantation techniques.

PMID- 15567541
TI  - Computational simulation of axial dynamization on long bone fractures.
AB  - BACKGROUND: Axial dynamization has been shown in previous studies to promote
      callus formation, improve bone healing at fracture sites, and enhance bone
      remodeling. However, the possibility of non-axial movements or uniform fracture
      site compression during dynamization, and the appropriate relaxation of fixator
      joints to achieve such function, have not been investigated. METHODS: This study
      used previously developed computational models based on two commercially
      available unilateral external fixators (Dynafix and Orthofix) to analyze the
      fixator joint adjustments used and the fracture site movements generated during
      dynamization. FINDINGS: When none of the fixator's sliding joints were parallel
      to the long bone axis, significant non-axial movements occurred during
      dynamization. The dual sliding joint design of the Dynafix fixator was beneficial
      in reducing these non-axial movements. When all of the fixator joints were
      allowed to adjust simultaneously during dynamization, exact axial movement or
      uniform compression at a complicated fracture site was achievable.
      INTERPRETATION: This study revealed that significant non-axial movements may
      occur during dynamization, and that such a deficiency can be corrected by
      relaxing certain fixator joints in addition to the sliding mechanism. The same
      modeling technique can also be applied in bone lengthening application to assure
      desirable limb alignment during the distraction process. These analysis results
      can aid the performance assessment of an external fixator and facilitate
      appropriate application of such a device to achieve either active or controlled
      axial movement.

PMID- 15567542
TI  - Asymmetrical fracture fixation: stability of oblique fractures is influenced by
      orientation.
AB  - BACKGROUND: Although clear differences in fracture site displacement have
      previously been demonstrated between transverse and oblique fracture models
      stabilised by an asymmetrical method, the direction of the obliquity has not been
      examined biomechanically. METHODS: Eight Sawbones tibiae were cut to represent
      oblique fractures: four ran from antero-inferior to postero-superior and four
      from antero-superior to postero-inferior. These were fixed with a Sheffield Ring
      Fixator and cyclically loaded in axial and off-axis compression. Direct
      measurements were taken of inter-fragmentary displacement. RESULTS: Significant
      differences were detected between the fracture directions (P < 0.01) and inter
      fragmentary displacements were generally reduced in antero-superior to postero
      inferior fractures compared with antero-inferio to postero-superior fractures.
      INTERPRETATION: Fixation asymmetries need to be tailored to specific fracture
      orientation to improve fracture site mechanics.

PMID- 15567543
TI  - Altered hamstring-quadriceps muscle balance in patients with knee osteoarthritis.
AB  - BACKGROUND: To compare hamstring to quadriceps muscle coactivity during level
      walking, stair ascent, and stair decent between individuals with and without knee
      osteoarthritis. METHODS: In a cross-sectional study, subjects with grade II knee
      osteoarthritis (n = 26), healthy age- and gender-matched (n = 20) and healthy,
      young adults (n = 20) performed three activities of daily living. During the
      stance phase of these activities surface electromyography was measured. Two
      coactivity ratios were computed, the biceps femoris to vastus lateralis ratio and
      the ratio of the biceps femoris EMG activity relative to the EMG activity
      measured during contraction- and velocity-specific maximal voluntary biceps
      femoris contraction, i.e., biceps femoris to maximal biceps femoris activity.
      FINDINGS: Subjects with knee osteoarthritis had significantly higher coactivity
      than age-matched healthy adults and young adults and healthy adults had more
      coactivity than young adults regardless the type of coactivity ratio. The biceps
      femoris to vastus lateralis ratio yielded 25% higher coactivity value than the
      biceps femoris to maximal biceps femoris ratio (P < 0.0001). The EMG activity of
      the vastus lateralis relative to maximal vastus lateralis EMG activity was 92% in
      subjects with knee osteoarthritis, 57% in age-matched controls, and 47% in young
      adults (P < 0.0001). INTERPRETATION: Patients with knee osteoarthritis revealed
      increased hamstring muscle activation while executing activities of daily living.
      Altered muscle activation at the knee may interfere with normal load distribution
      in the knee and facilitate disease progression. Therapeutic interventions should
      focus not only on quadriceps strengthening but also on improving muscle balance
      at the knee.

PMID- 15567544
TI  - Modifying center of mass trajectory during sit-to-stand tasks redistributes the
      mechanical demand across the lower extremity joints.
AB  - OBJECTIVE: Sit-to-stand tasks are commonly facilitated by modifying the initial
      position of the center of mass relative to the feet. It was hypothesized that
      modifications in the center of mass trajectory during sit-to-stand tasks altered
      the total body momentum at seat departure and redistributed the lower extremity
      net joint moments. DESIGN: Between-task within-subject comparison was employed
      using a robust statistical method to accommodate for small sample size. METHODS:
      Six individuals performed four sit-to-stand tasks with systematic modifications
      in the initial center of mass position by varying the orientation of the lower
      extremity segments. The momentum of the center of mass and lower extremity net
      joint moments were quantified and compared. RESULTS: Reducing the horizontal
      center of mass displacement significantly reduced horizontal total body momentum
      required at seat departure. Sit-to-stand tasks initiated with more horizontal
      shank and thigh positions required significantly greater knee and hip extensor
      net joint moments than those with more vertical shank and thigh positions. Sit-to
      stand tasks initiated with vertical shank positions also required significantly
      greater hip extensor net joint moments as compared to those with more horizontal
      shank orientations. INTERPRETATION: When changes in initial center of mass
      position are made, alteration in center of mass horizontal momentum and the
      orientation of the lower extremity segments relative to the reaction force are
      observed. Consequently, mechanical demand imposed on the ankle, knee, and hip
      joint is redistributed. The magnitude of the net joint moments is dependent on
      the segment orientation, the reaction force, and the adjacent net joint moment.

PMID- 15567545
TI  - Changes in distal muscle timing may contribute to slowness during sit to stand in
      Parkinsons disease.
AB  - OBJECTIVE: To compare patterns of muscle activation in the lower extremity and
      subsequent forces during sit to stand in persons with Parkinsonism. BACKGROUND:
      There is an interruption of the tibialis anterior/soleus interaction during
      forward oriented movements in some subjects with Parkinsonism, including sit to
      stand. This task is a major determinant of independence and 44% of those with
      Parkinsonism report difficulty. METHODS: 41 subjects with Parkinsonism were asked
      to stand up from a bench. Peak acceleration and vertical ground reaction forces,
      the slopes to these peaks, and the timing of events were measured. Surface
      electrodes were placed on tibialis anterior and soleus. RESULTS: The slower group
      produced force at slower rate than the fast group. The slower group spent 64% of
      the time taken to stand to complete the flexion-momentum phase, and the fast
      group spent 56%. The slower group had a larger proportion of co-contraction
      trials than the other groups. CONCLUSIONS: Slower subjects took longer to perform
      the task due to a longer time for seat off. Deficits recruiting tibialis anterior
      may contribute to the decreased rate of production of the acceleration forces and
      the longer time required for seat off. Relevance Decreased rate of rise of force
      is used to identify fallers in the elderly and subjects with stroke. Decreased
      rates of force production may therefore assist in identifying those with
      Parkinsonism at risk of falls. Treatment strategies designed to facilitate
      tibialis anterior activation may improve the functional performance of this task.

PMID- 15567546
TI  - Neurological complications in renal failure: a review.
AB  - Neurological complications whether due to the uremic state or its treatment,
      contribute largely to the morbidity and mortality in patients with renal failure.
      Despite continuous therapeutic advances, many neurological complications of
      uremia, like uremic encephalopathy, atherosclerosis, neuropathy and myopathy fail
      to fully respond to dialysis. Moreover, dialytic therapy or kidney
      transplantation may even induce neurological complications. Dialysis can directly
      or indirectly be associated with dialysis dementia, dysequilibrium syndrome,
      aggravation of atherosclerosis, cerebrovascular accidents due to ultrafiltration
      related arterial hypotension, hypertensive encephalopathy, Wernicke's
      encephalopathy, hemorrhagic stroke, subdural hematoma, osmotic myelinolysis,
      opportunistic infections, intracranial hypertension and mononeuropathy. Renal
      transplantation itself can give rise to acute femoral neuropathy, rejection
      encephalopathy and neuropathy in graft versus host disease. The use of
      immunosuppressive drugs after renal transplantation can cause encephalopathy,
      movement disorders, opportunistic infections, neoplasms, myopathy and progression
      of atherosclerosis. We address the clinical, pathophysiological and therapeutical
      aspects of both central and peripheral nervous system complications in uremia.

PMID- 15567547
TI  - Function localisation in neurosurgery: new tools, new practices?

PMID- 15567548
TI  - Magnetic source imaging supports clinical decision making in glioma patients.
AB  - OBJECTIVE: This study addresses the potential utility of preoperative functional
      imaging with magnetoencephalography (MEG) for the selection of glioma patients
      who are likely to benefit from resective surgical treatment regarding
      postoperative morbidity. METHODS: One hundred and nineteen patients with gliomas
      adjacent to sensorimotor, visual and speech related brain areas were investigated
      preoperatively with a MAGNES II biomagnetometer. In each patient the pre-surgical
      evaluation was focussed on the visual, sensorimotor cortex and/or of the speech
      related brain areas. A grading system was then used according to the distance of
      the MEG activation sources to the nearest tumour border to determine the further
      treatment. The therapeutic options consisted in conservative treatment,
      stereotactic biopsy and/or a radiation and chemotherapy, substantial
      cytoreduction and the gross total removal of the lesion. RESULTS: From 119
      investigated patients, 55 patients (46.2%) were not considered for surgery due to
      tumour invasion to functional cortex. Sixty four patients (53.8%) were chosen for
      resective surgery. In the surgical group only four patients (6.2%) suffered from
      neurological deterioration. CONCLUSIONS: Magnetic source imaging (MSI) proved to
      be a valuable help in the clinical decision making process of lesions adjacent to
      functional important brain areas. The relative high number of patients in whom
      MSI warns of the postoperative crippling sequelae may lead to a better selection
      of patients who benefit from resective surgery. This method may help to find the
      patients for whom conservative treatment seems to be more favourable concerning
      quality of life in the surviving time.

PMID- 15567549
TI  - A review of isolated third nerve palsy without subarachnoid hemorrhage using
      computed tomographic angiography as the first line of investigation.
AB  - INTRODUCTION: Digital subtraction angiography is recognized as the standard
      investigation for isolated third nerve palsy thought to be caused by an expanding
      aneurysm. We reviewed our experience in using computed tomographic angiography
      (CTA) as the first line investigation for patients presenting with isolated third
      nerve palsy without subarachnoid hemorrhage. METHOD: We retrieved the medical
      records of 34 patients who had presented with isolated third nerve palsy without
      associated subarachnoid hemorrhage to our institution between January 1998 and
      July 2001. The clinical history, course and outcome as well as the radiological
      data was reviewed. RESULTS: A total of nine structural lesions (26%) were noted
      as the etiology of the third nerve palsy. All of the five posterior communicating
      artery aneurysms were picked up by the CTA. Neither the presence nor the absence
      of painful complete third nerve palsy was of diagnostic value for intracranial
      aneurysm. CONCLUSION: A good quality CTA is sufficient to detect a compressive
      aneurysm and may detect other structural lesions. This allows neurosurgeons to
      plan the management of patients with isolated third nerve palsy. Patients in whom
      CTA results are inconclusive should be further investigated with catheter
      angiography.

PMID- 15567550
TI  - Oropharyngeal dysphagia in polymyositis/dermatomyositis.
AB  - The nature of the oropharyngeal dysphagia in polymyositis/dermatomyositis (PM/DM)
      has been investigated by EMG methods. Nineteen patients with PM/DM were studied.
      The oropharyngeal phase of swallowing was evaluated by the electrophysiological
      methods measuring the laryngeal relocation time, pharyngeal transit time and the
      triggering of the pharyngeal phase of swallowing reflex. The EMG of
      cricopharyngeal muscle of the upper esophageal sphincter was also recorded in 10
      patients. The patients have been compared with a group of 22 healthy controls
      matched with age and gender. Dysphagia limit was also measured for all patients
      and control subjects. Fourteen out of 19 patients could not swallow 20 ml or less
      amount of water at one go and divided the bolus into two or more pieces
      (piecemeal deglutition) in comparison to normal subjects. In PM/DM patients, the
      triggering of the swallowing reflex for the voluntarily initiated swallow was
      normal while the pharyngeal phase of swallowing was significantly prolonged. The
      cricopharyngeal sphincter muscle EMG demonstrated severe abnormalities in halves
      of the patients investigated. These findings demonstrated the weakness of the
      striated oropharyngeal muscles. Cricopharyngeal sphincter muscle was affected
      less frequently and showed either hyperreflexic or hyporeflexic states during
      swallowing. It is concluded that the pharyngeal stage of oropharyngeal swallowing
      is mainly involved in patients with PM/DM.

PMID- 15567551
TI  - Predictive value of white blood cell count on admission for in-hospital mortality
      in acute stroke patients.
AB  - OBJECTIVE: In the present study, we sought to determine the predictive value of
      white blood cell (WBC) count measured on admission for in-hospital death in acute
      stroke patients. METHODS: WBC count was measured automatically in 400 consecutive
      acute stroke patients (67.5 +/- 12.9 years old; 226 female) on admission to
      hospital. Patients included into the study had symptoms starting less than 12 h
      prior to hospitalization and no known causes of inflammation. Logistic regression
      adjusted for age, gender, the presence of diabetes, hypertension, atrial
      fibrillation, previous stroke and ischemic heart disease was used for the
      calculation of odds ratio (OR) with 95% confidence interval (CI) for in-hospital
      mortality. RESULTS: Stroke patients with WBC counts in the third tertile (over
      9.7 x 10(3) microL(-1)) had more than eight times (OR: 8.26; 95% CI: 3.95-17.25;
      P < 0.0001) increased risk of in-hospital mortality as compared with the rest of
      the patients. The WBC count increment of every 1000 cell/microL was associated
      with OR for in-hospital death of 1.27 (95% CI: 1.17-1.39; P < 0.0001). There was
      also a significant correlation between patients' WBC count and their clinical
      condition and degree of disability at the time of admission to hospital.
      CONCLUSION: An increased WBC count within the first 12 h of onset of an ischemic
      stroke is a strong prognostic factor for in-hospital mortality.

PMID- 15567552
TI  - Venlafaxine versus amitriptyline in the prophylactic treatment of migraine:
      randomized, double-blind, crossover study.
AB  - In patients with migraine with or without aura the prophylactic effect of
      amitriptyline (AMT) and venlafaxine (VLF) was compared in a randomized double
      blind crossover study. Intolerable side effects resulted in drop out of five
      patients on AMT (due to hypersomnia, difficulty in concentration and orthostatic
      hypotension) and one patient on VLF (because of nausea and vomiting). Following
      the run-in period the patients (n = 52) were randomly treated with one of the
      study medications for 12 weeks. After a wash-out period lasting 4 weeks the
      patients were treated with the other drug for further 12 weeks. Both drugs had
      significant beneficial effect on pain parameters. Total number of side effects of
      VLF was low when compared with the side effect profile of AMT. In conclusion, it
      is suggested that VLF may be considered for the prophylaxis of migraine because
      of its low and/or tolerable side effect properties.

PMID- 15567553
TI  - Altered expression of Cx43 in astrocytic tumors.
AB  - OBJECTIVE: To evaluate the Cx43 expression of astrocytic tumors and correlate
      their expression with degrees of malignancy and proliferation activity of tumors.
      METHODS: Cx43 expression in eight normal brain tissues, 44 freshly resected
      astrocytic tumor specimens and four malignant glioma cell lines were examined by
      Northern blot analysis and immunohistochemical staining. The proliferation
      activity of tumors was measured by Ki67 labeling index (Ki67LI) with
      immunostaining. Scrape loading and dye transfer assay was used for examination of
      gap junction intercellular communication (GJIC) in glioma cell lines. RESULTS:
      Twenty-three out of 44 astrocytic tumors (52%) expressed both Cx43 mRNA and
      Protein. Cx43 expression was decreased with the ascending of tumor grade and
      negatively correlated with Ki67LI. GJIC was interrupted in glioma cell lines
      deficient in Cx43 expression. CONCLUSIONS: Cx43 expression level is inversely
      correlated with the tumor grade and proliferation activity of tumor, suggesting
      the potential role of Cx43 in the malignant progression of astrocytic tumors.

PMID- 15567554
TI  - Primary central nervous system lymphoma report of 32 cases and review of the
      literature.
AB  - We retrospectively analyzed 32 cases of primary central nervous system lymphoma
      (PCNSL). Five cases were diagnosed in the period 1987-1994, for 27 cases in the
      period 1995-2002. There were 17 men and 15 women whose median age was 69 years.
      Three patients were immunodeficient. The commonest symptoms were focal deficit
      (16 patients) and cognitive/behaviour disturbances (14 patients). Radiologically,
      a total of 47 contrast-enhancing lesions were observed in 32 patients; 18
      patients had deep-seated lesions. All but two patients underwent histological
      diagnosis following craniotomy (11 patients) and/or stereotaxic biopsy (22
      patients); diagnosis was obtained on CSF cytology in one patient with a third
      ventricle tumour. In the last patient, the diagnosis was based on the finding of
      marked tumour shrinkage under corticotherapy, despite two negative histological
      examinations. Treatment included surgical resection (10 patients), chemotherapy
      (25 patients) and/or radiotherapy (12 patients). According to the therapeutic
      recommendations of the GELA (Groupe d'Etude des Lymphomes de l'Adulte), 19
      patients received at least two courses of high-dose methotrexate; intrathecal
      chemotherapy was used in 20 patients with methotrexate and/or cytosine
      arabinoside. Radiation therapy consisted of whole brain irradiation followed by a
      boost on tumour site. Nine patients received a combined treatment of chemotherapy
      and radiotherapy. Twelve patients showed rapid progression to death. At the time
      of last contact, 28/32 patients (88%) had died, all from PCNSL disease or from
      complications due to its treatment. The median survival time was 13.9 months. We
      conclude that PCNSL is an increasingly frequent tumour. The diagnosis is obtained
      by stereotactic biopsy in the majority of cases. The prognosis appears dismal
      despite an intensive multidisciplinary therapeutic approach.

PMID- 15567555
TI  - Clinical features of 1039 patients with neurophysiological diagnosis of carpal
      tunnel syndrome.
AB  - PURPOSE: To describe the clinical features of patients with a neurophysiologic
      diagnosis of carpal tunnel syndrome (CTS) in the state of Rio Grande do Sul,
      Brazil. METHODS: We prospectively studied 1039 patients with a neurophysiologic
      diagnosis of CTS in southern Brazil. All patients completed a
      clinicoepidemiological questionnaire which included a drawing of the arm and
      hand, in which they were asked to paint the areas in which paresthesia and pain
      occurred. In part of the sample, we also investigated the presence of clinical
      signs such as Tinel's, Phalen, and tenar atrophy. The diagnosis of CTS was
      performed using a predetermined neurophysiological protocol. RESULTS: A total of
      1528 hands were diagnosed with CTS. The severity of CTS was mild in 42% of cases,
      moderate in 18% and severe in 40%. Patients had a mean age of 48.3 +/- 12.4 years
      old, and a ratio of 5.6 females to 1 male was observed. Symptoms restricted to
      the hand and wrist was observed in 51.8% of cases with paresthesia and in 18.5%
      of cases with pain. In 92.5% of the partially affected hands, paresthesia was
      present in at least one of the first three fingers, while pain affected the three
      first fingers in 78.8% of these hands. Pain with a distribution which did not
      involve the hand occurred in 18.5% of cases, while paresthesia without
      involvement of the hand occurred in only 1.9%. Distribution of symptoms,
      according to Katz's hand diagram, showed a classic pattern in 12.6% of affected
      hands, a pattern classified as probable CTS in 66.3%, and an unlikely CTS pattern
      in 4.1%. Tinel's and Phalen's sign were observed in 34.2 and 56.3% of the hands,
      respectively. CONCLUSION: The clinical presentation of CTS is pleomorphic,
      ranging from the absence of symptoms to very severe cases. This variation
      probably is dependent on coexistent diseases, such as tendinitis and
      fibromyalgia, as well as on subjective aspects of the patients.

PMID- 15567556
TI  - Presumed pharmacologically induced change from upbeat- to downbeat nystagmus in a
      patient with Wernicke's encephalopathy.
AB  - A case of Wernicke's encephalopathy due to proven thiamine deficiency suffering
      from upbeat nystagmus (UN) changing to downbeat nystagmus (DN) after a latency of
      1 year is presented. The case was also notable for the finding of positive
      oligoclonal bands in the CSF. The underlying pathophysiological mechanisms and a
      possible effect of baclofen treatment are discussed.

PMID- 15567557
TI  - Citalopram-induced jaw tremor.
AB  - A variety of medications can induce or enhance a tremor. Tremors most commonly
      affect the limbs, especially the arms. We report a patient who presented with a 5
      6 Hz jaw tremor with a temporal association with the administration of
      citalopram. To our knowledge, this is the first report in literature, of a
      transient jaw tremor associated with citalopram. According to the current data,
      citalopram-induced jaw tremor can be explained by an indirect inhibitory effect
      on central dopaminergic activity.

PMID- 15567558
TI  - Response of neuropeptide Y-induced feeding to mu-, delta- and kappa-opioid
      receptor antagonists in the neonatal chick.
AB  - It is known that opioid antagonists reduce the orexigenic effect of neropeptide Y
      (NPY) in mammals. We studied the effect of three opioid antagonists on NPY
      induced feeding in male broiler chicks. Beta-funaltrexamine (beta-FNA),
      naloxonazine (NAL), ICI-174,864 (ICI) or nor-binaltorphimine (nor-BNI),
      antagonists of mu-, mu1-, delta- or kappa-receptors, and NPY were co-injected in
      chicks. Food intake was measured 30 min after treatment. Co-injection of beta-FNA
      or NAL was effective in reducing NPY-induced feeding, whereas ICI and nor-BNI had
      little effect on NPY-induced feeding. These data suggest that the mu-opioid
      receptor, especially the mu1-opioid has some relation to NPY-induced feeding, and
      implies that an endogenous ligand, such as beta-endorphin, participates in the
      orexigenic effect of NPY in neonatal chicks.

PMID- 15567559
TI  - Augmented breath phase volume and timing relationships in the anesthetized rat.
AB  - Augmented breaths (ABs), or sighs, are airway protective reflexes and part of the
      normal repertoire of respiratory behaviors. ABs consist of two phases, where
      phase I volume and timing resembles preceding eupnic breaths, and phase II is an
      augmenting motor pattern and occurs at the end of phase I. Recent evidence
      suggest multiple respiratory motor patterns can occur following dynamic
      functional reconfiguration of one respiratory neural network. It follows that the
      response of the respiratory network to modulatory inputs also may undergo dynamic
      reconfiguration. We hypothesized that lung-volume related feedback during ABs
      would alter AB timing differentially during phase I and II. We measured phase I
      and II volumes and durations in urethane anesthetized rats with decreased lung
      volume secondary to three models of varying phrenic motor impairment (spinal
      injury alone, unilateral phrenicotomy, and combined injuries). AB phase I and II
      inspired volume were decreased after phrenic motor impairment (p<0.05). In
      contrast, only phase I duration following injury was altered compared to
      controls. Phase II duration remaining unchanged despite the greatest effect of
      injury on volume occurring during phase II. Thus, sigh volume-timing
      relationships differ between phases of an augmented breath suggesting that the
      response of the respiratory network to modulatory inputs has changed. These data
      support the hypothesis that multiple respiratory behaviors occur following
      dynamic reconfiguration of the respiratory neural network.

PMID- 15567560
TI  - Effects of Pavlovian fear conditioning on septohippocampal metabolism in rats.
AB  - The effects of classical fear conditioning in different regions of the limbic
      system were analysed using cytochrome oxidase (CO) histochemistry. Wistar rats
      were submitted to different conditions. Rats in the group Paired received tone
      shock pairing, to elicit conditioned suppression of lever pressing (i.e., tone
      will evoke conditioned fear responses). The group Unpaired underwent random
      presentations of these stimuli and developed no conditioned fear. Untrained
      animals were also included as a control group. A significant decrease in CO
      activity was found in the medial septal area and the dorsal hippocampus (CA3
      subfield and dentate gyrus) in the group Paired as compared with the group
      Unpaired. Furthermore there was greater metabolic activity in the control group
      as compared with the other two groups. No differences in CO labelling of the
      basolateral amygdala were detected among all groups. These findings suggest that
      the septohippocampal system plays an important role in controlling conditioned
      fear behaviour.

PMID- 15567561
TI  - Delayed rectifier potassium currents and Kv2.1 mRNA increase in hippocampal
      neurons of scopolamine-induced memory-deficient rats.
AB  - To explore the ionic mechanisms of memory deficits induced by cholinergic lesion,
      whole-cell patch clamp recording techniques in combination with single-cell RT
      PCR were used to characterize delayed rectifier potassium currents (IK) in
      acutely isolated hippocampal pyramidal neurons of scopolamine-induced cognitive
      impairment rats. Scopolamine could induce deficits in spatial memory of rats. The
      peak amplitude and current density of IK measured in hippocampal pyramidal
      neurons were increased from 1.2+/-0.6 nA and 38+/-19 pA/pF of the control group
      (n=12) to 1.8+/-0.5 nA and 62+/-24 pA/pF (n=48, P<0.01) of the scopolamine
      treated group. The steady-state activation curve of IK was shifted about 8 mV
      (P<0.01) in the direction of hyperpolarization in scopolamine-treated rats. The
      mRNA level of Kv2.1 was increased (P<0.01) in the scopolamine-treated group, but
      there was no significant change of Kv1.5 mRNA level. The present study
      demonstrated for the first time that IK was enhanced significantly in hippocampal
      pyramidal neurons of scopolamine-induced cognitive impairment rats. The increase
      of Kv2.1 mRNA expression in hippocampal pyramidal cells might be responsible for
      the enhancement of IK and could be the ionic basis of the memory deficits induced
      by scopolamine.

PMID- 15567562
TI  - Expression of neuronal markers during NTera2/cloneD1 differentiation by cell
      aggregation method.
AB  - Human teratocarcinoma NTera2/cloneD1 (NT2) cells are able to generate postmitotic
      neurons in response to retinoic acid (RA) and for this reason these cells provide
      an important tool to study human neurogenesis in vitro. We have obtained neurons
      by treating NT2 aggregated cells with RA for solely 14 days. RT-PCR assays showed
      that NT2 cells express mRNAs of several neural bHLH genes such as Hes1, Ngn1,
      Mash1, NeuroD, Math1 and Pax6, just in the early days of RA exposure. In
      particular, we reported for the first time that RA treatment was followed by a
      modulation of endogenous Ngn1 and Math1 transcripts. RT-PCR and Western blotting
      experiments also demonstrated expression of typical neuronal markers such as
      GluR, MAP2, Tau and NeuN. Knowledge of the expression pattern of the different
      neuronal genes during NT2 commitment could be used to investigate alterations in
      the molecular pathways involved in the human neuronal differentiation.

PMID- 15567563
TI  - Nicastrin gene polymorphisms, cognitive ability level and cognitive ageing.
AB  - The hypothesis that polymorphisms in the gene for nicastrin (NCSTN) are
      associated with differences in cognitive level and ageing was tested in 462
      relatively healthy surviving participants of the Scottish Mental Survey 1932.
      None had a history of dementia. They were tested on the Moray House Test of
      verbal reasoning at age 11 in 1932 and at age 79 between 1999 and 2001. At age 79
      they also took tests of non-verbal reasoning, short- and long-term verbal
      declarative memory, Verbal Fluency, and a short screening test for dementia.
      Subjects who possessed at least one copy of the NCSTN B haplotype (Hap B) had
      higher scores on the Moray House Test (a test principally of verbal reasoning) at
      age 11 (p=0.036) and age 79 (p=0.027). The effect of Hap B on cognition at age 79
      was non-significant after adjusting for the effect at age 11. Therefore, the
      effect of Hap B in this sample is on the life-long stable trait of cognitive
      ability, and not on age-related cognitive change. The possibility that this
      result might be a selection effect was not supported by the samples being in
      Hardy-Weinberg equilibrium with respect to the distribution of NCSTN genotypes.

PMID- 15567564
TI  - NF-kappaB precursor, p105, and NF-kappaB inhibitor, IkappaBgamma, are both
      elevated in Alzheimer disease brain.
AB  - The nuclear factor-kappaB (NF-kappaB) signal transduction pathway regulates
      several vital cellular processes. During our studies of the glycoproteins
      involved in Alzheimer disease (AD), we found a significant increase of a 45-kDa
      protein band that was stained by lectin Maackia amurensis agglutinin (MAA). Mass
      spectrometry and Western blot analyses indicated that this 45-kDa MMA-positive
      protein was an inhibitor of NF-kappaB, IkappaBgamma. By Western blot analysis,
      the levels of both IkappaBgamma and NF-kappaB precursor, p105, were found to be
      elevated in AD brain as compared to age-matched controls. Our findings suggest
      that the NF-kappaB pathway might be involved in the molecular mechanism of AD.

PMID- 15567565
TI  - Enhanced hippocampal long-term potentiation in rats after chronic exposure to
      homocysteine.
AB  - Homocysteine (HCY) is a sulphur-containing amino acid, which has been linked to
      neurodegenerative diseases such as Alzheimer's disease, and is widely reported to
      enhance vulnerability of neurons to oxidative, excitotoxic and apoptotic injury
      via perturbed calcium homeostasis, activation of N-methyl-D-aspartate (NMDA) and
      metabotropic glutamate (mGlu) receptors. The present study was undertaken to
      investigate the effects of HCY on long-term potentiation (LTP) and synaptic
      transmission after chronic 4-week systemic exposure to HCY in adult rats, and
      possible longer-term effects of HCY 4 weeks after exposure had ended. Contrary to
      expectation, LTP was enhanced, not retarded after chronic HCY exposure relative
      to controls. Basic synaptic transmission was not affected at this time point.
      However, after the 4-week wash out period, a decrease in speed of basic synaptic
      transmission emerged, and LTP was still partially enhanced, particularly for time
      points >30 min post-tetanus. In summary, we provide first evidence for sustained
      HCY-induced changes in hippocampal plasticity and a slow-onset disruption in
      synaptic transmission. These changes may reflect the suggested (excito-)toxicity
      of HCY and its putative contribution to neurodegenerative disease.

PMID- 15567566
TI  - Stability of neuropathic pain symptoms in partial sciatic nerve ligation in rats
      is affected by suture material.
AB  - Many factors affect the development of neuropathic pain behavior in animal
      models. In this letter, we describe the differences in the development of
      neuropathic pain behavior observed when the partial sciatic nerve ligation (PNL)
      is performed with either a synthetic silk or chromic catgut ligation. To
      characterize nociceptive changes over time after surgery, neutral plate, hot
      plate, Von Frey, pinprick, acetone spray and cold plate testing was performed.
      The results indicated that a chromic catgut ligature caused cold allodynia,
      chemical hyperreactivity, mechanical hyperalgesia and hypersensitivity that
      remained present for the entire 56 days post-surgical observation period. With
      the synthetic silk ligature, comparable functional deficits were present in the
      initial phase after surgery, but several of these deficits diminished over time
      21-28 days post-surgery. In conclusion, performing the PNL using chromic catgut
      suture thread gives rise to more robust sensory deficits than when synthetic silk
      is used. Therefore, the material that is used for the ligature in the partial
      sciatic ligation model has an effect on the outcome of the observed sensory
      abnormalities.

PMID- 15567567
TI  - Separate sets of neurons of the central nucleus of the amygdala project to the
      substantia innominata and the caudal pontine reticular nucleus in the rat.
AB  - The central nucleus of the amygdala (CeA) is generally regarded as a control
      nucleus of subcortical target systems. Due to its widespread projections to
      different brain areas it is able to modulate emotional behavior of the organism.
      However, it is still not clear whether single neurons of the CeA project to
      different areas or to one target area. Injections of the retrograde tracers
      Fluorogold and True Blue into target regions of the central nucleus of the
      amygdala, i.e., the substantia innominata (SI) and the caudal pontine reticular
      nucleus (PNC), revealed overlapping but otherwise distinct neuronal populations
      within mainly the medial division of the CeA. From our study we conclude that SI
      and PNC receive input from different subsets of amygdala neurons.

PMID- 15567568
TI  - Distribution of facial motor neurons in the pond turtle Pseudemys scripta
      elegans.
AB  - A tract tracing study was performed to examine the localization of the facial
      nucleus in the brain stem of the pond turtle, Pseudemys scripta elegans.
      Neurobiotin and the fluorescent tracers alexa fluor 488 and 594 were used to
      retrogradely label neurons of the abducens or facial nerves. The results showed
      that the facial nucleus has two subnuclei, a medial group and a lateral group.
      Measurements of cell size revealed no significant differences between these
      populations. Double labeling studies showed that the medial cell group of the
      facial nucleus lies between the principal and accessory abducens nuclei in the
      pons, whereas the lateral group lies adjacent to the accessory abducens nucleus.
      The facial nucleus of pond turtles largely overlaps the rostrocaudal extent of
      the accessory abducens nucleus, but extends well beyond it into the medulla.
      These data elucidate the position and distribution of the facial nucleus in the
      brain stem of pond turtles and contribute to the body of comparative
      neuroanatomical literature on the distribution of the cranial nerve nuclei of
      reptiles.

PMID- 15567569
TI  - Reinnervation of motor units in intrinsic muscles of a transplanted hand.
AB  - Functional recovery of transplanted hand can be evaluated clinically but until
      now there has been no direct assessment of muscle control. In October 2000 we
      transplanted the right hand of a brain-dead man aged 43 onto a man aged 35 who
      had lost his right dominant hand 22 years before. Starting from day 205 after the
      transplant, multi-channel surface electromyographic (EMG) signals were recorded
      from intrinsic muscles of the transplanted hand in order to assess their degree
      of reinnervation. Eleven months post-operatively, the first motor unit action
      potential train was detected from the abductor digiti minimi. One month later,
      also the abductor pollicis brevis and the opponens pollicis muscles showed motor
      unit activity, while, after 15 and 24 months, the first dorsal interosseous and
      the first lumbricalis muscles, respectively, showed activation of their first
      motor units. An increase in the number of active motor units was observed after
      the first signs of reinnervation, although the process was rather slow. In
      sustained maximal contractions, the motor unit discharge rate decreased from
      (mean +/- S.D.) 34.0+/-6.7 pps to 23.4+/-5.1 pps in 60 s for the abductor digiti
      minimi, although the subject was verbally encouraged to maintain a maximal
      activation. Moreover, the subject was able to perform basic control tasks
      involving voluntary modulation of motor unit discharge rate. With a visual
      feedback, he could increase discharge rate of the abductor digiti minimi
      approximately linearly over time, from 13.4+/-6.7 pps to 32.5+/-11.2 pps in 60 s.
      In conclusion, we showed reinnervation of single motor units in a transplanted
      hand after 22 years of denervation. Moreover, voluntary modulation of discharge
      rates of these motor units could be performed since the first sign of
      reinnervation.

PMID- 15567570
TI  - Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra
      foliacea metabolite.
AB  - The effects of various Flustra foliacea metabolites on different types of human
      neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes
      were investigated. Whereas most of the compounds tested had a small blocking
      effect, one of them, deformylflustrabromine, selectively increased the current
      obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The
      current increase was reversible and concentration-dependent. This potentiating
      effect was still present at saturating concentrations of acetylcholine, and no
      changes in single-channel conductance or reversal potential were observed, thus
      suggesting a modification in the gating of alpha4beta2 receptors. Dwell time
      analysis of single channel records indicates that the mechanism of action of
      deformylflustrabromine could be both an increase of the opening rate constant and
      a decrease of the closing rate constant on alpha4beta2 receptors. Thus,
      deformylflustrabromine may constitute an excellent starting point for the future
      development of related agents able to potentiate human neuronal nicotinic
      receptor function.

PMID- 15567571
TI  - Similar dynamics of G-protein coupled receptors molecules in response to
      antagonist binding.
AB  - In this communication we would like to draw attention on surprisingly similar
      transition of G-protein coupled receptors (GPCR) molecules, observed in these
      kinetic studies made with different receptors and their antagonists.

PMID- 15567572
TI  - Perceptual-motor organization of children's catching behaviour under different
      postural constraints.
AB  - The experiment investigates the perceptual-motor organization underlying
      children's catching performance when the demands on the postural system are
      varied. For this purpose, one-handed catching performance was observed under
      different postural constraints in children aged 9-10 years. Two groups of eleven
      participants, classified as either good or poor catchers, performed one-handed
      catches under three different postural conditions: standing, sitting, and
      standing while pressing a button positioned to a postural support aid (PSA).
      Results revealed, first, that when seated, poor catchers approached the level of
      the good catchers' performance. Second, poor catchers improved their performance
      by using the PSA, but not to the same performance as when sitting. Third, there
      was no effect of postural condition on the performance of the good catchers. The
      performance increase in the poor catchers is attributable to a combined change in
      functional postural sway and better timed movement of the catching hand, made
      possible by exploiting the extra surface support area afforded by sitting.

PMID- 15567573
TI  - Molecular mechanisms responsible for microglia-derived protection of Sprague
      Dawley rat brain cells during in vitro ischemia.
AB  - Microglia-derived protection of brain cells (microglia, astrocytes, and neurons)
      during in vitro ischemic stress (deprivation of glucose, oxygen, and serum) was
      determined. Trypan blue exclusion assay, immunoblocking assay, Western blot
      analysis, and ELISA assay were used to determine the molecular mechanisms
      responsible for the microglia-derived protection. Results demonstrated that
      supernatants from the ischemic microglia protected all three cell-types from
      ischemia-induced damage by releasing the transforming growth factor-beta1 (TGF
      beta1) and glial cell line-derived neurotrophic factor (GDNF). The protection of
      microglia was TGF-beta1 related, whereas astrocytes protection was GDNF
      dependent. The protection of neurons was TGF-beta1 and GDNF independent, and the
      molecular nature responsible for their protection remains to be determined. These
      results indicate contribution from the surrounding cells and the types of
      receptors expressed on different brain cells probably also play an important role
      in determining their fate against ischemia.

PMID- 15567574
TI  - Importance of anesthesia for the genesis of neurogenic pulmonary edema in spinal
      cord injury.
AB  - There are reports describing both provocation and inhibition of neurogenic
      pulmonary edema by anesthetic drugs. Therefore, we compared the effect of two
      types of anesthesia on the formation of neurogenic pulmonary edema in rats with
      balloon-induced acute spinal cord injury. Animals with sham procedure (group 1)
      were anesthesized by intraperitoneal sodium pentobarbital. In the experimental
      groups, rats were submitted to acute spinal cord lesion by insufflations of a
      balloon in the epidural space at T8 for 1 min (group 3 under i.p. sodium
      pentobarbital and group 2 under i.p. xylazine-ketamine anesthesia). In rats with
      pentobarbital anesthesia, systolic blood pressure doubled the baseline value
      during compression, whereas this effect was less pronounced in the ketamine
      xylazine group. The pulmonary index (100 x wet lung weight/body weight) was 0.395
      (+/-0.018) in sham-operated rats, rose to 0.499 (+/-0.060) in group 2, and was
      maximum under pentobarbital anesthesia (0.639+/-0.14; p=0.0018). Histologic
      examination of the spinal cord showed parenchymal ruptures and acute hemorrhage.
      Comparison of the pulmonary index with histologic slides of lung parenchyma
      revealed that relevant intra-alveolar edema occurred only for index values above
      0.55. On electron microscopy, endothelial alterations, and damage of the alveolar
      lining cells were found. Our study indicates that neurogenic pulmonary edema
      caused by spinal cord injury is less pronounced in rats under xylazine-ketamine
      anesthesia, when compared with pentobarbital.

PMID- 15567576
TI  - Factors contributing to the public health and economic importance of waterborne
      zoonotic parasites.
AB  - This is the first of a series of review articles in a Special Issue publication
      on waterborne zoonotic parasites. A brief historical overview of the occurrence
      and importance of waterborne parasites, dating from early civilization is
      presented. The article considers the diversity of parasites including protozoa,
      nematodes, cestodes and trematodes and the related zoonotic organism
      microsporidia. Many of the life cycle stages and their characteristics, which
      make parasites environmentally resistant and suitable for waterborne transmission
      are discussed. Surfaces of transmission stages consist of multiple layers of
      proteins, lipids, chitin or other substances capable of withstanding a variety of
      physical and chemical treatments. Delivery of waterborne parasites is facilitated
      by various mass distribution systems to consumers, and by transport and
      intermediate hosts such as fish and filter-feeding invertebrates which are
      consumed by humans. The article discusses the trends in global warming and
      climate change and potential for concurrent rise in waterborne disease outbreaks
      due to parasites. Impacts of technological modernization and globalization on the
      transmission of zoonotic waterborne zoonotic parasites are considered, including
      the effects of large-scale agricultural practices, rapid transportation of goods,
      and widespread movement of individuals and animals. Finally, transmission
      features and parasite attributes which contribute to concerns about accidental or
      orchestrated waterborne disease outbreaks are discussed.

PMID- 15567577
TI  - The zoonotic significance and molecular epidemiology of Giardia and giardiasis.
AB  - The taxonomy and molecular epidemiology of Giardia and Giardia infections are
      reviewed in the context of zoonotic and waterborne transmission. Evidence to
      support the zoonotic transmission of Giardia is very strong, but how frequent
      such transmission occurs and under what circumstances, have yet to be determined.
      Zoonotic origin for waterborne outbreaks of Giardia infection appears to be
      uncommon. Similarly, livestock are unlikely to be an important source of
      infection in humans. The greatest risk of zoonotic transmission appears to be
      from companion animals such as dogs and cats, although further studies are
      required in different endemic foci in order to determine the frequency of such
      transmission.

PMID- 15567578
TI  - Cryptosporidium: a water-borne zoonotic parasite.
AB  - Of 155 species of mammals reported to be infected with Cryptosporidium parvum or
      C. parvum-like organisms most animals are found in the Orders Artiodactyla,
      Primates, and Rodentia. Because Cryptosporidium from most of these animals have
      been identified by oocyst morphology alone with little or no host specificity
      and/or molecular data to support identification it is not known how many of the
      reported isolates are actually C. parvum or other species. Cryptosporidiosis is a
      cause of morbidity and mortality in animals and humans, resulting primarily in
      diarrhea, and resulting in the most severe infections in immune-compromised
      individuals. Of 15 named species of Cryptosporidium infectious for nonhuman
      vertebrate hosts C. baileyi, C. canis, C. felis, C. hominis, C. meleagridis, C.
      muris, and C. parvum have been reported to also infect humans. Humans are the
      primary hosts for C. hominis, and except for C. parvum, which is widespread
      amongst nonhuman hosts and is the most frequently reported zoonotic species, the
      remaining species have been reported primarily in immunocompromised humans. The
      oocyst stage can remain infective under cool, moist conditions for many months,
      especially where water temperatures in rivers, lakes, and ponds remain low but
      above freezing. Surveys of surface water, groundwater, estuaries, and seawater
      have dispelled the assumption that Cryptosporidium oocysts are present
      infrequently and in geographically isolated locations. Numerous reports of
      outbreaks of cryptosporidiosis related to drinking water in North America, the
      UK, and Japan, where detection methods are in place, indicate that water is a
      major vehicle for transmission of cryptosporidiosis.

PMID- 15567579
TI  - Toxoplasmosis - a waterborne zoonosis.
AB  - Humans become infected with Toxoplasma gondii mainly by ingesting uncooked meat
      containing viable tissue cysts or by ingesting food or water contaminated with
      oocysts from the feces of infected cats. Circumstantial evidence suggests that
      oocyst-induced infections in humans are clinically more severe than tissue cyst
      acquired infections. Until recently, water-borne transmission of T. gondii was
      considered uncommon but a large human outbreak linked to contamination of a
      municipal water reservoir in Canada by wild felids and the widespread infection
      by marine mammals in the USA provide reasons to question this view. The present
      paper reviews information on the biology of oocyst-induced infections of T.
      gondii in humans and animals and examines possible importance of transmission by
      water.

PMID- 15567580
TI  - Cyclospora cayetanensis, a food- and waterborne coccidian parasite.
AB  - Food- and waterborne coccidia including Cryptosporidium parvum, Cyclospora
      cayetanensis, Sarcocystis hominis and Sarcocystis suihominis, and Isospora belli
      are cyst-forming apicomplexan protozoa that cause intracellular infections,
      predominantly in the epithelial cells of the intestine. They are transmitted by
      oocysts from person-to-person by the fecal-oral route or via contaminated water
      or food. The most common symptom of infection is diarrhea, however, asymptomatic
      infections occur. Infections are associated with intestinal inflammation, with
      pathological lesions such as villus blunting, and abnormal function such as
      malabsorption. Mild-to-moderate, self-limiting diarrhea is common in healthy
      individuals ingesting infective stages of these organisms. However, patients with
      immune dysfunction can have severe intestinal injury and prolonged diarrhea.
      Diagnosis in many cases is made by a microscopic examination of the stool, and
      the use of appropriate staining techniques, but more recently molecular methods
      for detection are used increasingly. Effective antimicrobial treatment for
      prolonged infection in immunocompromised patients is available for most of these
      infections. These gastrointestinal coccidial pathogens have important
      similarities in epidemiology, disease pathogenesis, clinical manifestations,
      diagnosis, and treatment. Although there are many other cyst-forming coccidia of
      public health, veterinary and/or economic importance, discussion in this chapter
      will be limited to C. cayetanensis, as an important example of the group. Aspects
      of the biology, epidemiology, diagnosis, disease, treatment and control are
      considered. This parasite is considered to be an emerging pathogen. From 1990 to
      2000, there were 11 foodborne outbreaks of cyclosporosis in North America that
      affected at least 3600 people. There are many outstanding questions regarding
      this parasite and under-reporting is common because general diagnostic methods
      for intestinal parasites are inadequate for detection of Cyclospora.

PMID- 15567581
TI  - Amebae and ciliated protozoa as causal agents of waterborne zoonotic disease.
AB  - The roles free-living amebae and the parasitic protozoa Entamoeba histolytica and
      Balantidium coli play as agents of waterborne zoonotic diseases are examined. The
      free-living soil and water amebae Naegleria fowleri, Acanthamoeba spp., and
      Balamuthia mandrillaris are recognized etiologic agents of mostly fatal amebic
      encephalitides in humans and other animals, with immunocompromised and
      immunocompetent hosts among the victims. Acanthamoeba spp. are also agents of
      amebic keratitis. Infection is through the respiratory tract, breaks in the skin,
      or by uptake of water into the nostrils, with spread to the central nervous
      system. E. histolytica and B. coli are parasitic protozoa that cause amebic
      dysentery and balantidiasis, respectively. Both intestinal infections are spread
      via a fecal-oral route, with cysts as the infective stage. Although the amebic
      encephalitides can be acquired by contact with water, they are not, strictly
      speaking, waterborne diseases and are not transmitted to humans from animals. Non
      human primates and swine are reservoirs for E. histolytica and B. coli, and the
      diseases they cause are acquired from cysts, usually in sewage-contaminated
      water. Amebic dysentery and balantidiasis are examples of zoonotic waterborne
      infections, though human-to-human transmission can occur. The epidemiology of the
      diseases is examined, as are diagnostic procedures, anti-microbial interventions,
      and the influence of globalization, climate change, and technological advances on
      their spread.

PMID- 15567582
TI  - Blastocystis in humans and animals: new insights using modern methodologies.
AB  - Among the waterborne protozoan parasites of medical and veterinary importance,
      Blastocystis is perhaps one of the less well-understood. However, in recent
      years, there has been a surge of interest in the organism, fueled in part by the
      possible association of Blastocystis infection with intestinal disorders, and its
      unusual taxonomic affiliations. Although there is information on the parasite's
      morphology, taxonomy and mode of transmission, its pathogenicity, life cycle, and
      function of certain organelles continue to baffle investigators. The clinical
      relevance of Blastocystis will be better answered once an animal model is found.
      Blastocystis infections have a worldwide distribution but prevalence is highest
      in areas with poor hygiene and deficient sanitation services and facilities.
      Application of modern molecular tools has advanced knowledge of the organism's
      genetic diversity, taxonomy and zoonotic potential.

PMID- 15567583
TI  - Epidemiology of microsporidiosis: sources and modes of transmission.
AB  - Microsporidia are single-celled, obligate intracellular parasites that were
      recently reclassified from protozoa to fungi. Microsporidia are considered a
      cause of emerging and opportunistic infections in humans, and species infecting
      humans also infect a wide range of animals, raising the concern for zoonotic
      transmission. Persistent or self-limiting diarrhea are the most common symptoms
      associated with microsporidiosis in immune-deficient or immune-competent
      individuals, respectively. Microsporidian spores appear to be relatively
      resistant under environmental conditions, and species of microsporidia infecting
      humans and animals have been identified in water sources, raising concern about
      water-borne transmission. Sensitive and specific immunomagnetic bead separation
      and PCR-based methods are being developed and applied for detecting microsporidia
      in infected hosts and water sources for generating more reliable prevalence data.
      The most effective drugs for treating microsporidiosis in humans currently
      include albendazole, which is effective against the Encephalitozoon species but
      not against Enterocytozoon bieneusi, and fumagillin, which has broader anti
      microsporidia activity but is toxic in mammals, suggesting a need to identify
      better drugs. Strategies to capture and disinfect microsporidia in water are
      being developed and include filtration, coagulation, chlorination, gamma
      irradiation, and ozonation.

PMID- 15567584
TI  - Waterborne zoonotic helminthiases.
AB  - This review deals with waterborne zoonotic helminths, many of which are
      opportunistic parasites spreading directly from animals to man or man to animals
      through water that is either ingested or that contains forms capable of skin
      penetration. Disease severity ranges from being rapidly fatal to low-grade
      chronic infections that may be asymptomatic for many years. The most significant
      zoonotic waterborne helminthic diseases are either snail-mediated, copepod
      mediated or transmitted by faecal-contaminated water. Snail-mediated
      helminthiases described here are caused by digenetic trematodes that undergo
      complex life cycles involving various species of aquatic snails. These diseases
      include schistosomiasis, cercarial dermatitis, fascioliasis and fasciolopsiasis.
      The primary copepod-mediated helminthiases are sparganosis, gnathostomiasis and
      dracunculiasis, and the major faecal-contaminated water helminthiases are
      cysticercosis, hydatid disease and larva migrans. Generally, only parasites whose
      infective stages can be transmitted directly by water are discussed in this
      article. Although many do not require a water environment in which to complete
      their life cycle, their infective stages can certainly be distributed and
      acquired directly through water. Transmission via the external environment is
      necessary for many helminth parasites, with water and faecal contamination being
      important considerations. Human behaviour, particularly poor hygiene, is a major
      factor in the re-emergence, and spread of parasitic infections. Also important in
      assessing the risk of infection by water transmission are human habits and
      population density, the prevalence of infection in them and in alternate animal
      hosts, methods of treating sewage and drinking water, and climate. Disease
      prevention methods, including disease surveillance, education and improved
      drinking water treatment are described.

PMID- 15567585
TI  - Concentrating, purifying and detecting waterborne parasites.
AB  - There has been recent emphasis on developing better methods for detecting
      diseases of zoonotic and veterinary importance. This has been prompted by an
      increase in human disease agents detectable in environmental samples, the
      potential for bioterrorism, and the lowering of international trade barriers and
      expansion of personal travel, which are bringing previously considered exotic
      diseases to new geographical localities. To appreciate the complexities of
      developing detection methods and working with environmental samples, it is
      appropriate to review technologies currently in use, as well as those in
      development and presently limited to research laboratories. Discussion of
      parasite detection would not be possible without including methods for parasite
      sampling, concentration, and purification because it is often necessary to
      process large sample volumes prior to analysis, and no reliable methods are
      available for significantly amplifying parasites in vitro. Reviewing proven
      methods currently in use will provide a baseline for generating, accepting and
      implementing the more sensitive and specific methods under development today.

PMID- 15567586
TI  - Drinking water treatment processes for removal of Cryptosporidium and Giardia.
AB  - Major waterborne cryptosporidiosis and giardiasis outbreaks associated with
      contaminated drinking water have been linked to evidence of suboptimal treatment.
      Cryptosporidium parvum oocysts are particularly more resistant than Giardia
      lamblia cysts to removal and inactivation by conventional water treatment
      (coagulation, sedimentation, filtration and chlorine disinfection); therefore,
      extensive research has been focused on the optimization of treatment processes
      and application of new technologies to reduce concentrations of viable/infectious
      oocysts to a level that prevents disease. The majority of the data on the
      performance of treatment processes to remove cysts and oocysts from drinking
      water have been obtained from pilot-tests, with a few studies performed in full
      scale conventional water treatment plants. These studies have demonstrated that
      protozoan cyst removal throughout all stages of the conventional treatment is
      largely influenced by the effectiveness of coagulation pretreatment, which along
      with clarification constitutes the first treatment barrier against protozoan
      breakthrough. Physical removal of waterborne Crytosporidium oocysts and Giardia
      cysts is ultimately achieved by properly functioning conventional filters,
      providing that effective pretreatment of the water is applied. Disinfection by
      chemical or physical methods is finally required to inactivate/remove the
      infectious life stages of these organisms. The effectiveness of conventional
      (chlorination) and alternative (chlorine dioxide, ozonation and ultra violet [UV]
      irradiation) disinfection procedures for inactivation of Cryptosporidium has been
      the focus of much research due to the recalcitrant nature of waterborne oocysts
      to disinfectants. This paper provides technical information on conventional and
      alternative drinking water treatment technologies for removal and inactivation of
      the protozoan parasites Cryptosporidium and Giardia.

PMID- 15567587
TI  - Quality assurance considerations for detection of waterborne zoonotic parasites
      using Cryptosporidium oocyst detection as the main example.
AB  - A laboratory quality assurance (QA) program can minimize errors and provide
      confidence in the validity of laboratory test results. The structure of a QA
      program varies somewhat among laboratories but usually requires addressing a QA
      manual, QA goals, quality of resources, standard operating procedures, internal
      quality control, and external QA procedures. This paper reviews these general
      components and discusses some of the more particular QA considerations specific
      to filtration, immunomagnetic separation (IMS), immunofluorescence microscopy
      (FA), vital dye staining, differential interference contrast (DIC) microscopy,
      and molecular methods, which are involved in the detection and enumeration of
      Cryptosporidium oocysts.

PMID- 15567588
TI  - Prevalence of antibodies to Toxoplasma gondii and intestinal parasites in stray,
      farm and household cats in Spain.
AB  - Seroprevalence of Toxoplasma gondii was tested for in 585 cats in different
      regions of Spain. Sera were tested by the indirect immunofluorescence antibody
      test (IFAT). Specific antitoxoplasma IgG (IFAT titer>or=1/80) were found in 189
      of 585 (32.3%): 117 of 317 (36.9%) stray cats, 16 of 48 (33.3%) farm cats and 56
      of 220 (25.5%) household cats. The overall prevalence was significantly higher in
      stray groups (36.4% of 365) than in household cats (25.5% of 220), higher in
      adult cats (>6 months old, 36.8% of 443) than in juvenile cats (<6 months old,
      13.9% of 101), and higher in male stray cats (45.3% of 128) than in female stray
      cats (32% of 153). Prevalence of intestinal parasites was also analysed by a
      routine coprological method in 382 of the 585 cats. Intestinal parasites were
      found in 107 faecal samples (28%): 76 of 231 (32.9%) stray cats, 14 of 48 (29.2%)
      farm cats and 17 of 103 (16.5%) household cats. T. gondii oocysts were not found
      in any faecal samples analysed. The following prevalences of other intestinal
      parasites were found: Toxocara cati (18.3%), Toxascaris leonina (1.3%),
      Ancylostoma sp. (1%), Capillaria spp. (1.3%), Aelurostrongylus abstrusus (1%),
      Taenia like (3.7%), Dipylidium caninum (2.6%) and Cystoisospora spp. (6.3%).

PMID- 15567589
TI  - Elaboration of a crude antigen ELISA for serodiagnosis of caprine neosporosis:
      validation of the test by detection of Neospora caninum-specific antibodies in
      goats from Sri Lanka.
AB  - The protozoan parasite N. caninum is a major pathogen in cattle and dogs.
      However, clinical symptoms are occasionally described for other potential hosts.
      Natural abortion in goats due to N. caninum has been rarely reported and only
      little data is available on the seroprevalence of N. caninum in this species. In
      the present study, 486 goats from Sri Lanka were tested in a crude antigen ELISA
      for the presence of serum antibodies against N. caninum. Additionally, the sera
      were analysed by N. caninum-Western blot and indirect fluorescence antibody test
      (IFAT). In all three tests applied, only three sera (0.7%) were scored clearly
      positive for anti-N. caninum antibodies. The optimal correlation between ELISA,
      IFAT, and Western blot confirms the suitability of the ELISA for large-scale
      seroepidemiologic studies, not only in cattle but also in goats.

PMID- 15567590
TI  - Isolation of Neospora caninum from a calf in Malaysia.
AB  - In order to attempt isolate the protozoan parasite Neospora caninum, an N.
      caninum seropositive pregnant Sahiwal Friesian cross heifer from a large-scale
      dairy farm in Malaysia was kept for observation until parturition at the
      Veterinary Research Institute, Ipoh. The heifer gave birth to a female calf that
      was weak, underweight and unable to rise. Precolostral serum from the calf had an
      N. caninum indirect fluorescent antibody test titre of 1:3200. It died 12 h after
      birth and necropsy was performed. Brain homogenate from the calf was inoculated
      into 10 BALB/c mice that were kept for 3 months after which brain tissue from the
      mice was inoculated onto 24 h fresh monolayer Vero cell lines. The cell cultures
      were examined daily until growth of intracellular protozoa was observed. DNA of
      the organisms from the cell cultures was analyzed by PCR and DNA sequencing. DNA
      fragments of the expected size were amplified from the isolate using N. caninum
      specific primers, and sequence analysis of ITS1 clearly identified the isolate as
      N. caninum. This is the first successful isolation of N. caninum from a bovine in
      Malaysia, and the isolate is designated Nc-MalB1.

PMID- 15567591
TI  - Cross-sectional survey in pig breeding farms in Hesse, Germany: seroprevalence
      and risk factors of infections with Toxoplasma gondii, Sarcocystis spp. and
      Neospora caninum in sows.
AB  - A cross-sectional survey was performed to estimate the prevalences of antibodies
      to Toxoplasma gondii (ELISA, IFAT), Sarcocystis spp. (ELISA, using S.
      miescheriana as antigen) and Neospora caninum (ELISA, immunoblotting) in sows
      from breeding farms in southern Hesse, Germany. A total of 2041 plasma samples of
      sows from 94 randomly selected farms was examined. Data on farm profiles,
      husbandry management and sows were collected by a questionnaire and exploratively
      analysed. For T. gondii the ELISA results agreed well with the results obtained
      by IFAT (kappa=0.71). Antibodies to T. gondii were detected by ELISA in 19% of
      the sows. Sixty-nine percent of the farms had at least one seropositive sow, and
      a within-farm seroprevalence of >or=50% was observed in 14% of all farms. The
      prevalence of anti-T. gondii antibodies was positively correlated with the age of
      sows. The within-herd seroprevalence was significantly higher in farms with
      reproductive disorders than in those without such problems. On the farm level,
      the farm type 'piglet production' (versus 'pedigree breeding' or 'farrow-to
      finish') was the only risk factor associated with the presence of T. gondii
      seropositive sows. Antibodies to Sarcocystis spp. were found in 29% of the sows.
      Seventy-two percent of the farms harboured at least one seropositive sow, and a
      within-farm seroprevalence of >or=50% was detected in 23% of all farms. The
      seroprevalence increased significantly with the age of sows. On the farm level,
      only the farm type 'piglet production' (versus 'pedigree breeding') and the
      replacement of sows by purchasing (versus raising on the own farm) were
      identified as risk factors for seropositivity. Antibodies to N. caninum were
      detected in one sow using both the screening ELISA and the confirmatory
      immunoblotting technique. This may indicate the first natural N. caninum
      infection in pigs.

PMID- 15567592
TI  - Vaccination of mice and sheep with Fh12 FABP from Fasciola hepatica using the new
      adjuvant/immunomodulator system ADAD.
AB  - We evaluate the ability of a Fasciola hepatica FABP native antigen (Fh12) with a
      new vaccination system called ADAD to protect mice and sheep against an
      experimental F. hepatica infection. The vaccination protocol consists of a set of
      two injections. The first injection contains a micelle in which two components
      are included, saponin from Quillaja saponaria (Qs) and/or Anapsos (A) a
      Polypodium leucotomos hydroalcoholic extract, both emulsified in a non-mineral
      oil (Montanide) in a water/oil emulsion (30/70). This is subcutaneously injected
      to achieve the "adaptation" of the immune system to subsequent stimuli. The
      second injection contains in addition the Fh12 antigen. Two different experiments
      were carried out using two mouse strains (BALB/c and CD-1). Mice vaccinated with
      Qs+A+Fh12 presented a survival rate of 40%, when compared with control groups.
      Furthermore, we evaluated the efficiency of the vaccination in sheep against an
      experimental F. hepatica challenge. The vaccinated sheep presented lower fluke
      recovery (24.5%), number of eggs in bile fluid (58.1%) and faeces (40.3%) than
      control groups. The recovered flukes were shorter (32.7%), immature (34.0%) and
      with lower body mass (31.6%) than non-complete vaccinated sheep. Thus, the new
      ADAD system could be a good alternative for future vaccination experiments
      against fasciolosis.

PMID- 15567593
TI  - Evaluation of biological control of sheep parasites using Duddingtonia flagrans
      under commercial farming conditions on the island of Gotland, Sweden.
AB  - Field trials, conducted over 3 consecutive years, were aimed at assessing farmer
      opinions of the practicality and effectiveness of using Duddingtonia flagrans to
      control nematode parasites in their flocks on the Swedish island of Gotland.
      These trials were also monitored by intensive parasitological investigation. On
      Gotland, lambing occurs in spring, and around mid-summer (late June), ewes and
      lambs are moved to saved pastures due to pasture deterioration caused by dry
      conditions. Weaned lambs are then returned to original lambing pastures in early
      autumn for finishing. One farm (B) was used for 2001-2003 and a second farm (N)
      was also used in 2002 and 2003. On each farm, two flocks (each of 20 ewes + twin
      lambs) were managed separately, namely: fungus group which received a daily
      supplement + fungal spores from lambing until the summer move (6 weeks) and:
      control group which received supplement only. For Farm B, the numbers of lambs
      that were marketed prior to the end of the grazing season, were 13, 18, 19 for
      the fungus treatment whereas corresponding numbers for the control treatment were
      8, 16 and 11 for years 2001, 2002 and 2003, respectively. Final weights of the
      remaining lambs at the end of each year were also consistently heavier, and the
      numbers of lambs retained for finishing during winter were less, on the fungus
      treatment compared with the control treatment. On Farm N, similar results were
      recorded, with more lambs marketed earlier in the fungus group (25 and 19)
      compared with the control (19 and 15) in 2002 and 2003, respectively. The weights
      of the remaining lambs at the end of the trial in 2003 showed a 4.5 kg weight
      gain advantage of the fungus group compared to the controls. Tracer tests during
      autumn 2001 on Farm B, showed that Teladorsagia circumcincta plus
      Trichostrongylus spp. levels were significantly less on the fungus treatment
      (P=0.018). The summer/autumn of 2002 was one of the driest on record for Gotland.
      This resulted in very low levels of infective larval availability. But on both
      farms, T. circumcincta numbers were less on the fungus than on the control
      paddocks (P=0.048 on Farm B). In 2003 very low numbers of infective larvae were
      recorded in the autumn tracers for both treatments on both farms. Both farmer co
      operators were encouraged with these results and consider that biological control
      of nematode parasites in their flocks, using D. flagrans, is of practical value.

PMID- 15567594
TI  - Circulation of Toxocara spp. in suburban and rural ecosystems in the Slovak
      Republic.
AB  - Toxocara spp., the common roundworms of domestic and wild animals, are the
      causative agents of larval toxocarosis in humans. The migration of Toxocara
      larvae in men causes clinical syndrome, called larva migrans visceralis or larva
      migrans ocularis. The objective of the present work was to investigate the
      prevalence of toxocarosis in dogs, red foxes (Vulpes vulpes), and small mammals
      in the Slovak Republic. T. canis infection was diagnosed in 16.6% out of 145 dogs
      examined. Young animals showed significantly higher positivity (50.0%) than
      adults (12.4%). Coprological investigation of 310 red foxes showed 8.1%
      prevalence of T. canis, with higher occurrence in animals from rural conditions
      (8.6%) than from suburban environment (5.6%). Out of 710 small mammals examined,
      anti-Toxocara antibodies were detected in 7.7% of the animals. The most
      frequently seropositive species was Apodemus agrarius (15.9%). Seropositivity of
      small mammals from suburban localities was higher (10%) compared with rural areas
      (5.8%), with adult animals exhibiting higher seropositivity (8.0%) than subadults
      (6.8%). Our results have confirmed the importance of dogs, red foxes and small
      mammals in circulation of this serious helminthozoonosis in suburban and rural
      ecosystems.

PMID- 15567595
TI  - Effects of subcutaneous injections of a long acting moxidectin formulation in
      grazing beef cattle on parasite fecal egg reduction and animal weight gain.
AB  - Trials were conducted in Arkansas, Idaho, Illinois and Wisconsin using a common
      protocol to evaluate effectiveness and safety of a long acting (LA), oil-based
      injectable formulation of moxidectin in beef cattle grazing spring and/or summer
      pastures. At each site, 150 cattle (steers and/or heifers) were blocked based on
      pretreatment fecal strongyle egg counts (EPG) and then randomly assigned to
      treatments within blocks. Presence of naturally acquired parasitic infections,
      confirmed by presence of parasite eggs in feces, was a prerequisite for study
      enrollment. Within each block of three animals, two received moxidectin LA
      injectable on day 0 at a dosing rate of 1.0 mg moxidectin/kg b.w. into the dorsal
      aspect of the proximal third of the ear, and one received a placebo control
      treatment. Cattle were weighed before treatment and on day 55 or 56 (55/56) after
      treatment. Fecal samples were also collected from 10 randomly selected blocks of
      animals at each site on days 14, 28 and 55/56 for EPG quantification. Average
      daily gain (ADG) was computed over the posttreatment period. Data pertaining to
      ADG and EPG were combined across sites and analyzed by mixed model analysis of
      variance to assess the fixed effect of treatment and random effects of site,
      block within site and the treatment by site interaction. Compared to placebo
      treated controls, the geometric means of fecal EPG counts from cattle treated
      with moxidectin LA injectable were reduced 99.8% 14 days after treatment, 99.1%
      28 days after treatment and 96.7% 55/56 days after treatment. Rate of weight gain
      by cattle treated with moxidectin LA injectable was 0.59 kg/day, or 23% (0.11
      kg/day) more than placebo-treated controls (P<0.05). None of the cattle treated
      with moxidectin LA injectable exhibited signs of macrocyclic lactone toxicosis.
      Summarized across all study sites, proportions of cattle that received concurrent
      therapeutic treatments were similar among treatment groups. Study results
      demonstrate that moxidectin cattle LA injectable administered at a dosing rate of
      1.0 mg moxidectin/kg b.w. to grazing beef cattle was effective and safe.

PMID- 15567596
TI  - Examination of the migration of first instar larvae of the parasite OEstrus ovis
      (Linne 1761) [Diptera: OEstridae] in the upper respiratory tract of artificially
      infected lambs and daily measurements of the kinetics of blood eosinophilia and
      mucosal inflammatory response associated with repeated infection.
AB  - Twelve lambs were divided into two groups: Group C control, non-infected, and
      Group O infected once a week for 5 weeks with OEstrus ovis L1 through the same
      nostril. The first objective of this experiment was to check whether larvae
      moving through a given nostril remain in the same side nasal cavity or might to
      spread in both nasal cavities. It has been observed that larvae invade and spread
      through the entire nasal cavities. The only possible passage way between both
      sides is via the choanae and velum palatinum. The second objective was to follow
      the kinetics of blood eosinophilia. A primary peak in eosinophil numbers was
      noted 4 days following infection, with a higher peak following the second
      infection. After that, no major changes were seen. Nevertheless, the numbers of
      eosinophils were always higher than in control animals until the end of the
      follow-up. The third objective of the study was an enumeration of reactive cells
      (mast cells, globule leucocytes, and eosinophils) in the mucosae of the upper and
      lower respiratory tract after necropsy of the animals of the two groups. As
      observed in previous experiments, there was a large accumulation of these cells
      in mucosae of the upper respiratory tract. It was also worth noting a significant
      accumulation of eosinophils in the tissues of the trachea, bronchae and lungs
      even though OE. ovis was not present there. This "distant" eosinophilic reaction
      may have important consequences on patho-physiology of other parasites living in
      these locations: eosinophils have the potential to kill them even though these
      cells are not activated by their specific antigens.

PMID- 15567597
TI  - Velocity discrimination of auditory image moving in vertical plane.
AB  - This research investigated the ability of humans to discriminate changes in
      velocity of apparent movement of a sound source (as defined by the time required
      for the sound to traverse a 180 deg arc) in the median vertical plane. Apparent
      auditory movement was created by successive switching of the loudspeakers
      situated over the arc. The broadband noise with band width of 0.25-4 kHz (low
      pass noise - LP) and of 4-12.5 kHz (high-pass noise - HP) was employed as
      stimuli. Discrimination thresholds were calculated for reference velocities of 58
      and 115 deg/s under four stimuli types: movement of stepped movement of noise for
      low-pass noise and for high-pass noise and continuous motion for low-pass noise
      and for high-pass noise. The result showed that discrimination of the velocity
      depended on the signal frequency spectrum. The differential thresholds for the
      signals with low pass noise were significantly higher than those for signals with
      high pass noise (F(1;78) >> 3.96, p < 0.05). Magnitude of the absolute thresholds
      was the highest when the velocity was 115 deg/s for each of four types. It is
      interesting to note that the thresholds magnitude depended on the type of signal
      motion, that is on whether it was continuous or stepped.

PMID- 15567598
TI  - Round window membrane motion with air conduction and bone conduction stimulation.
AB  - The vibration patterns of the round window (RW) membrane in human cadaver
      temporal bone specimens were assessed by measurements of the velocity of
      reflective targets placed on the RW membrane with an approximate spacing of 0.2
      mm. The velocity was measured in the frequency range 0.1-10 kHz by a laser
      Doppler vibrometer in four specimens with air conduction (AC) stimulation and in
      four specimens with bone conduction (BC) stimulation. The response pattern was
      investigated by analyzing the velocity response of all targets on the RW
      membrane, by making iso-amplitude and iso-phase contour plots of the membrane
      surface, and by creating animations of the surface vibration at several
      frequencies. Similar response pattern was found with AC and BC stimulations. At
      frequencies below 1.5 kHz, the RW membrane vibrates nearly as a whole in an in
      and-out motion and above 1.5 kHz, the membrane moves primarily in two sections
      that vibrate with approximately 180 degrees difference. Indication of some
      traveling wave motion of the RW membrane at those frequencies was also found. At
      higher frequencies, above 3 kHz, the membrane motion is complex with a mixture of
      modal and traveling wave motion. An increase of the stimulation level did not
      alter the vibration pattern; it only gave an increase of the RW membrane
      vibration amplitude corresponding to the increase in stimulation. When the mode
      of stimulation at the oval window was altered, by the insertion of a 0.6 mm
      piston, the vibration pattern of the RW membrane changed.

PMID- 15567599
TI  - Tracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea.
AB  - Neurotrophin therapy in the cochlea can potentially slow or reverse the
      degeneration of the auditory nerve that occurs during progressive deafness.
      Studies were performed to trace the diffusion and uptake of neurotrophin-3 (NT-3)
      following infusion into the cochlea. NT-3 labeled with (125)I or coated onto
      fluorescent microspheres was introduced into the basal turn of normal hearing and
      deafened guinea pig cochleae via a single slow-rate injection. Cochleae were
      examined between 2 h and 28 days post-infusion by autoradiography or fluorescent
      microscopy to determine the number of turns labeled by NT-3, identify individual
      cells and tissues receiving NT-3 and quantify the proportion of signal in each
      tissue. In general, long-term infusions were required for all cochlear turns to
      receive NT-3. (125)I NT-3 signal was strongest in cells lining the perilymphatic
      space of the scala tympani, basilar membrane, osseous spiral lamina and spiral
      ligament. Signal in the peripheral nerve tract and Rosenthal's canal was only 1.3
      2.1 times background levels of radiation. NT-3 microspheres were detected within
      neural areas of the cochlea (nerve tract and Rosenthal's canal) in all cases, but
      not within neuronal cell bodies. NT-3 microspheres remained in the cochlea for at
      least 28 days, suggesting a low clearance rate within cochlear tissues.

PMID- 15567600
TI  - Down-regulation of otospiralin mRNA in response to acoustic stress in guinea pig.
AB  - Noise over-stimulation will induce or influence molecular pathways in the
      cochlea; one approach to the identification of the components of these pathways
      in the cochlea is to examine genes and proteins that change following different
      types and levels of stress. Quantitative reverse transcription polymerase chain
      reaction provides a method to look at differential expression of genes in the
      acoustic stress response. By using this technique we have revealed a down
      regulation of the level of otospiralin mRNA in the cochlea of guinea pigs after
      white noise over-stimulation for 2 h at 108 dB SPL. Otospiralin represents an
      inner ear specific protein found in fibrocytes of spiral limbus and spiral
      ligament in the cochlea, and some regions of the vestibule as the stroma
      underlying the utricle and crista sensory epithelia and the subepithelial layer
      of the walls of semicircular canals and maculae. It has been recently reported
      that transient down-regulation of otospiralin in guinea pigs causes vestibular
      syndrome and deafness. Our results suggest a possible role of this gene in
      response to acoustical stress, although the exact mechanism remains to be
      resolved.

PMID- 15567601
TI  - Morphological comparison of apoptotic with non-apoptotic dying cells in the
      developing inner ear of mouse embryos.
AB  - Dying cells studied by the TdT-mediated dUTP nick end-labeling (TUNEL) method
      have been classified as "apoptotic" and "non-apoptotic" cells. In this study, in
      which 12-day-old mouse embryos were used because of a high frequency of "natural
      cell death" due to changing inner ear morphology [Kaufman, M.H., 1992. The Atlas
      of Mouse Development, first ed., Academic Press, London, p. 147], the percentages
      of "apoptotic" and "non-apoptotic" dying cells (ADC and NADC) among total dying
      cells in the inner ear were calculated. Observation of consecutive paraffin
      sections showed about 90% of the dying inner ear cells to be ADC and about 10% to
      be NADC. ADC and NADC TUNEL positive dying cells in resin sections observed by
      light microscopy were examined again by transmission electron microscopy using a
      re-embedding procedure. ADC and NADC were then analyzed based on the
      classification of dying cells (types 1, 2, 3A, and 3B) as described by Clarke
      [Anat. Embryol. 181 (1990) 195]. It was clear that ADC were the equivalent of
      type 1 (apoptotic) dying cells and NADC were the equivalent of type 2
      (autophagic) dying cells. We consider these findings to be important baselines
      for determining the process underlying abnormal development of the inner ear and
      its functional disorders such as hearing loss.

PMID- 15567602
TI  - Feasibility of using silicon-substrate recording electrodes within the auditory
      nerve.
AB  - The use of penetrating, silicon-substrate (i.e., "thin-film") probes within a
      cross-section of a sensory nerve offers the possibility of assessing the pattern
      and extent of fiber excitation within the nerve. We used acute cat preparations
      to assess the feasibility of this technique for recordings within the auditory
      nerve trunk. Four probe configurations fabricated by the University of Michigan
      Center for Neural Communication Technology were evaluated using acoustic and
      electric stimuli. Our main concerns were the nature of the recorded potentials
      and the degree of spatial selectivity provided by these probes. We also made some
      basic assessments of electrode-tissue compatibility. The recorded potentials were
      characterized as field potentials with varying degrees of spatial selectivity. In
      some cases, responses to pure tones demonstrated good spatial selectivity, with
      unique responses recorded by different electrode sites. When electrode sites were
      positioned at different longitudinal positions along the nerve trunk, responses
      with latencies characteristic of each site were recorded. These results indicate
      that thin-film electrodes are capable of providing spatially specific response
      information from sensory nerves. However, in the case of feline auditory nerves,
      place-specific responses were inconsistently observed, making it difficult to use
      this technique to obtain detailed cochleotopic maps of neural excitation. More
      productive results may be possible from other peripheral nerves with less complex
      spatial arrangements of fibers.

PMID- 15567603
TI  - Chlorpromazine inhibits cochlear function in guinea pigs.
AB  - Outer hair cell (OHC) electromotility provides mechanical positive feedback that
      functions as the cochlear amplifier. In isolated OHCs, chlorpromazine shifts the
      electromotility voltage-displacement transfer function in a depolarizing
      direction without affecting its magnitude. This study sought to measure the
      effects of chlorpromazine on cochlear function in vivo. Salicylate, a drug that
      greatly reduces the magnitude of electromotility, was used for comparison.
      Perilymphatic perfusion of the guinea pig cochlea with chlorpromazine or
      salicylate increased the compound action potential (CAP) threshold across the
      frequency spectrum (1-20 kHz). Both drugs also increased distortion product
      otoacoustic emission (DPOAE) thresholds in the higher frequencies (10-20 kHz).
      Complete reversibility of these effects occurred after washout. Both drugs
      demonstrated concentration-dependent reductions in cochlear function that
      followed sigmoidal curves with similar fits to previously reported results in
      isolated OHCs. The endolymphatic potential was not affected by either of these
      drugs. Thus, chlorpromazine inhibits cochlear function in a manner consistent
      with what would be expected from data in isolated OHCs. This suggests that
      shifting the electromotility transfer function correspondingly reduces the gain
      of the cochlear amplifier.

PMID- 15567604
TI  - MMN to natural Arabic CV syllables: 1-normative data.
AB  - Mismatch negativity response parameters; latency, amplitude, and duration to
      natural Arabic CV syllables differing in durational change (Baa-Waa) and in
      spectrotemporal change (Gaa-Daa) were obtained from normal hearing young adult
      Egyptians. The aim was to get normative data for MMN response parameters and to
      find any differences between both primary and non-primary auditory pathways in
      encoding and processing speech signals. Statistically significant differences
      between durational and spectrotemporal contrasts for latency and duration were
      found. This was attributed to acoustic differences and to physiological
      differences between primary and non-primary auditory pathways.

PMID- 15567605
TI  - Intracochlear and extracochlear ECAPs suggest antidromic action potentials.
AB  - With experimental animals, the electrically evoked compound action potential
      (ECAP) can be recorded from multiple sites (e.g., round window, intracranial and
      intracochlear sites). However, human ECAPs are typically recorded from
      intracochlear electrodes of the implanted array. To bridge this difference, we
      obtained ECAPs from cats using both intracochlear and nerve-trunk recording
      sites. We also sought to determine how recording the site influences the acquired
      evoked potential and how those differences may provide insight into basic
      excitation properties. In the main experiment, ECAPs were recorded from four
      acutely deafened cats after implanting a Nucleus-style banded electrode array.
      Potentials were recorded from an electrode positioned on the nerve trunk and an
      intracochlear electrode. We manipulated stimulus level, electrode configuration
      (monopolar vs bipolar) and stimulus polarity, variables that influence the site
      of excitation. Intracochlear ECAPs were found to be an order of magnitude greater
      than those obtained with the nerve-trunk electrode. Also, compared with the nerve
      trunk potentials, the intracochlear ECAPs more closely resembled those obtained
      from humans in that latencies were shorter and the waveform morphology was
      typically biphasic (a negative peak followed by a positive peak). With anodic
      monophasic stimuli, the ECAP had a unique positive-to-negative morphology which
      we attributed to antidromic action potentials resulting from a relatively central
      site of excitation. We also collected intracochlear ECAPs from twenty Nucleus 24
      implant users. Compared with the feline ECAPs, the human potentials had smaller
      amplitudes and longer latencies. It is not clear what underlies these
      differences, although several factors are considered.

PMID- 15567606
TI  - Side-difference of vestibular evoked myogenic potentials in healthy subjects.
AB  - The aim of this study was to investigate the side-difference of vestibular evoked
      myogenic potentials (VEMPs) in relation to the provocation rates, latencies and
      amplitudes using binaural acoustic stimulation with bilateral recording. Fourteen
      healthy volunteers underwent a serial VEMP testings elicited binaurally by a
      sequence of alternating stimulus intensities, that is, 95-95 (right-left), 85-95,
      95-85, and 85-85 dBHL tone burst, respectively. The provocation rates as well as
      the mean latencies of p13 and n23 for the VEMPs demonstrated no significant side
      difference despite using 95-95, 85-95, 95-85 and 85-85 dBHL binaural acoustic
      stimulation. In contrast, nine (64%) of the 14 subjects showed side-difference of
      absolute p13-n23 amplitude, including right side dominant in five subjects, and
      left side dominant in four subjects. However, there was no significant side
      difference in terms of relative amplitude despite using 95-95, 85-95, 95-85 and
      85-85 dBHL binaural acoustic stimulation. Furthermore, the relative amplitude or
      interaural amplitude difference (IAD) ratios between those with and without side
      difference of p13-n23 amplitude did not differ significantly. Hence, this study
      provides a potentially important method for adjusting the side difference of p13
      n23 amplitudes by using a relative amplitude or IAD ratio adjustment. It also
      adds confidence to the successful use of binaural stimulation and recording of
      VEMPs under conditions of bilateral SCM muscular contractions.

PMID- 15567607
TI  - Organization of inhibitory feed-forward synapses from the dorsal to the ventral
      cochlear nucleus in the cat: a quantitative analysis of endings by vesicle
      morphology.
AB  - The main ascending, excitatory pathway from the cochlea undergoes synaptic
      interruption in the dorsal and ventral cochlear nuclei. The dorsal cochlear
      nucleus also forms a feed-forward circuit, which receives cochlear input and
      projects to the ventral cochlear nucleus by a tuberculo-ventral tract. This
      circuit may provide an inhibitory fringe (side bands) surrounding the center
      bands of the main ascending pathway. Biotinylated dextran injections into the
      dorsal cochlear nucleus anterogradely labeled the tuberculo-ventral tract and its
      endings in the anteroventral cochlear nucleus but also retrogradely filled
      cochlear nerve fibers and their terminals in the same regions. To distinguish
      tuberculo-ventral from cochlear nerve terminals, we used electron microscopy of
      the immunolabeled endings. Images were digitized and filter-enhanced, and the
      sizes and shapes of synaptic vesicles were used to construct quantitative
      profiles of the terminal types. The cochlear nerve endbulbs mapped to the same
      iso-frequency band of the injection site (main band). Flanking the main band were
      smaller labeled endings. About 45% of labeled terminals were pleomorphic and
      equally represented in the main band and side bands. Therefore, if there is an
      inhibitory fringe in the main projection pathway, it was not selective for
      tuberculo-ventral tract endings. Surprisingly, an excitatory category of round
      vesicles of intermediate size was labeled in the main band but not in the side
      bands. These intermediate endings may balance the feed-forward inhibition from
      the tuberculo-ventral tract. The quantitative method devised for classification
      of ending types by their vesicle profiles should be a generally useful tool for
      analysis.

PMID- 15567608
TI  - Effects of intensity and location on sound location discrimination in macaque
      monkeys.
AB  - Sound localization performance is degraded at low stimulus intensities in humans,
      and while the sound localization ability of humans and macaque monkeys appears
      similar, the effects of intensity have yet to be described in the macaque. We
      therefore defined the ability of four macaque monkeys to localize broadband noise
      stimuli at four different absolute intensities and six different starting
      locations in azimuth. Results indicate that performance was poorest at the lowest
      intensity tested (25 dB SPL), intermediate at 35 dB SPL, and equivalent at 55 and
      75 dB SPL. Localization performance was best at 0 degree (directly in front of
      the animal) and was systematically degraded at more peripheral locations (+/-30
      degrees and 90 degrees) and worst at a location directly behind the animal.
      Reaction times showed the same trends, with reaction times increasing with
      decreasing stimulus intensity, even under conditions where the monkey
      discriminated the location change with the same performance. These results
      indicate that sound level as well as position profoundly influences sound
      localization ability.

PMID- 15567609
TI  - Hemispheric asymmetry of the right ear advantage in dichotic listening.
AB  - ERP waveforms evoked by target-right and target-left stimuli in a directed
      attention, dichotic-listening paradigm were examined using cross-correlation
      analysis. We analyzed data from two experiments involving linguistic processing.
      They involved listening for (1) a phonemic feature, and (2) a series of morpho
      syntactic anomalies. The maximum correlation between target-right and target-left
      waveforms was achieved when the target-right waveform was delayed relative to the
      target-left waveform (the tau shift), reflecting the shorter latency of the
      target-right waveform. We interpret the direction of displacement as equivalent
      to a "right-ear advantage" in the dichotic listening paradigm. In both tasks, tau
      shifts were not uniformly distributed across the parietal electrode array. They
      were greatest on the extreme left side of the head and systematically declined as
      the electrode site moved rightward, indicating a temporal gradient in the
      relative latencies of the two waveforms. Results are interpreted in relation to
      both structural and attentional aspects of dichotic listening.

PMID- 15567610
TI  - Antioxidant protection in a new animal model of cisplatin-induced ototoxicity.
AB  - Mortality is a major complication in animal models of cisplatin-induced hearing
      loss due to the systemic toxicity of the drug. Here we report on a novel two
      cycle treatment in rats, each cycle consisting of four days of cisplatin
      injections (1 mg/kg, i.p., twice daily) separated by 10 days of rest. This
      regimen, similar to clinical courses of cancer chemotherapy, produced significant
      hearing loss without mortality. Auditory brain stem evoked responses were
      unchanged after the first cycle but were elevated by 40-50 dB at 16 and 20 kHz
      after the second. Loss of outer hair cells occurred after the second cycle,
      predominantly in the base of the cochlea. Total cochlear antioxidants declined
      progressively during drug treatment and were reduced to 60% of control values
      after the second cisplatin cycle. Co-administration of salicylate (100 mg/kg,
      s.c., twice daily) during both cycles or during the second cycle restored
      antioxidant levels and reduced cisplatin-induced threshold shifts. This model of
      cisplatin ototoxicity without mortality eliminates potentially confounding
      factors that may determine the survival of a special cohort of animals. The
      results also support the notion that reactive oxygen species are involved in
      cisplatin ototoxicity and show the potential usefulness of antioxidant treatment.

PMID- 15567611
TI  - Hearing in American leaf-nosed bats. III: Artibeus jamaicensis [Hearing Research
      184 (2003) 113-122].

PMID- 15567614
TI  - Course of the meatus acusticus internus as criterion for sex differentiation.
AB  - The importance of features that allow the determination of an individual's gender
      even with skulls that have been largely destroyed is undisputed in archaeological
      and anthropological practice. Due to its extreme mechanical strength, the pars
      petrosa ossis temporalis is usually preserved in skulls and the sex dimorphisms
      of this skeletal part are therefore of particular significance. In the present
      study, we aimed at clarifying the controversial question whether the course of
      the meatus acusticus internus (M.a.i.) beneath the superior surface also reveals
      sex-specific differences. Using 410 forensically modern petrous portions, the
      course of the canal was examined and the respective angles determined using a
      specifically developed casting and cutting technique. The median values certainly
      reveal sex differences: the lateral angle on the male petrous portions is 10
      degrees smaller than that of females; the medial angles on female petrous
      portions are approximately 5 degrees smaller than those of male skulls. Using
      discriminant analysis, approximately 66% of the specimens can be determined
      accurately.

PMID- 15567615
TI  - Metric analysis of sex differences in South African black and white pelves.
AB  - Sex determination of unknown skeletal material is one of the most vital
      determinations made by forensic anthropologists. Numerous studies have focussed
      on the differences, both osteometric and morphological, between the sexes of a
      particular racial phenotype and population. Previous work by a variety of
      researchers has underscored the necessity of population specific standards. The
      purpose of this research is to metrically assess sex differences in the pelvis of
      South African whites and blacks and develop standards tailored to these groups.
      Data were collected from 400 known sex/race skeletons from the Pretoria and Dart
      Collections. Nine measurements (traditional and newly developed) were taken and
      subjected to SPSS stepwise and direct discriminant analysis. Results indicated
      that there are significant differences (p < or = 0.001) between the sexes of both
      races for most measurements. Discriminant function analysis selected ischial
      length as the most sexually dimorphic dimension in whites (averaged 86%
      accuracy), while acetabulum diameter was most diagnostic in blacks (averaged 84%
      accuracy). Six functions were developed from the pelvic dimensions. Highest
      accuracy was achieved from Function 1 (including all dimensions) which averaged
      95.5% correct classification in whites and 94% in blacks. Functions based on
      selected parts of the pelvis were not as effective and ranged from 73-86% in
      whites and 72-84% in blacks. This research provided evidence of the significant
      sex differences that exist between the pelves of South African whites and blacks
      whilst measurements used here for discriminant function analysis gave
      classifications with high accuracies. These results can be used to aid in the
      identification of human skeletal remains in South Africa.

PMID- 15567616
TI  - Sex determination by discriminant analysis: an evaluation of the reliability of
      patella measurements.
AB  - Recently, a method which estimates the sex of unknown skeletal remains by
      discriminant function analysis of the patella has received much recognition. With
      seven simple measurements and a sexing accuracy of almost 84% this morphometric
      approach would be very suitable both in the forensic and anthropological context.
      In order to put this method to the test, 52 unfractured and non-pathological left
      and right patellae (26 males, 26 females) from a prehistoric skeletal sample were
      analyzed. In addition, 30 patellae were randomly selected which were not part of
      the original reference series. The first 15 (4 males, 11 females) had the same
      sample origin as the 30 target specimen but were of mediocre preservational
      state. The second 15 belonged to an archaeological sample of different
      provenience (8 males, 7 females). The results of the current study indicate that
      the morphometric assessment of this sesamoid is indeed well-suited as the results
      of the previous study could be duplicated, when sample size was not taken into
      consideration (85%). However, when the issue of small sample size was
      systematically addressed via a jack-knife procedure or the calculation of Delta
      value, the resultant accuracies dropped to 78 and 74%, respectively. It is
      suggested that two confounding factors--age and sex of the individual--may be
      held accountable. There are slight, whilst not statistically significant
      tendencies to misclassify female and older specimen.

PMID- 15567617
TI  - Triangle identified at the proximal end of femur: a new sex determinant.
AB  - Deviating from the conventional measurements, the present study uses the points
      of traction epiphysis on the upper end the femur as a landmark for measurement. A
      triangle was drawn on the posterior aspect of the femur using the apex of two
      traction epiphyses and the lateral most point on the articular margin of head.
      The study was conducted on 200 male and 80 female femora belonging to Central
      India. The lengths of triangle, so drawn, yielded highly significant results. The
      measurements were further evaluated by discriminant function analysis. Employing
      a single variable attained a prediction accuracy of 85.5% for males and 81.3% for
      females. When the variables were combined into a function, the accuracy improved
      to 86.5% for males and 86.3% for females. One of the advantages of the
      measurements on the proximal end of femur is that they can be used on fragmented
      bone where the shaft and distal end are missing. The study has applied value in
      the field of forensic anthropology.

PMID- 15567618
TI  - An evaluation of sex and body weight determination from the proximal femur using
      DXA technology and its potential for forensic anthropology.
AB  - Dual energy X-ray absorptiometry (DXA) is a rarely used technology in forensic
      anthropology. These densitometers quantify bone mineral density (BMD) and bone
      mineral content (BMC) and thus introduce new variables which are important for
      the application of forensic anthropology. This study investigates the importance
      of these variables and of this technology using bone scans of the proximal femur
      in sex and body weight determination. Two data sets from studies conducted at the
      University of Alabama at Birmingham were examined. The first study had 41 White
      patients, of which there were 17 males and 24 females, ranging in age from 61 to
      79 years and in weight from 99 to 242 lb. The following variables were utilized
      from the DXA scans: BMD in the femoral neck, greater trochanter and in Ward's
      triangle. A manual ruler in the software facilitated measurements on the minimum
      neck diameter and shaft diameter just below the lesser trochanter from each scan.
      The second study had 128 female patients, 71 of which were Black and 57 were
      White. They ranged in age from 23 to 47 1/2 years and they weighed between 31 1/2
      and 98 1/4 kg. The same variables were examined on these DXA scans as in the
      first study, with the addition of BMC of the femoral neck and the deletion of the
      minimum shaft diameter below the lesser trochanter. The first study showed
      statistically significant sex determination relationships (p < 0.02, t-tests for
      equality of means) at the supero-inferior femoral neck and lesser trochanter
      diameters, and from BMD at the femoral neck, trochanter, and Ward's triangle.
      Discriminant function analysis correctly classified sex over 92% of the original
      grouped cases using these variables. Multiple regression analysis using body
      weight as the dependent variable and various measures of the proximal femur as
      independent variables shows that while they are statistically significant and
      they have reasonably high R2 values up to 0.49; nevertheless, their standard
      errors of the estimates are too wide to be of much forensic use. The second study
      examined ethnic differences, Blacks and Whites, and body weight relationships in
      a larger, all female data set. Statistically significant differences between
      Blacks and Whites of BMD were found at Ward's triangle. Multiple regression
      analyses were again run on body weight and various measures of the proximal
      femur. The results were also broken down by ethnicity. Some body weight
      relationships were again statistically significant such as between the BMC of the
      femoral neck and the BMD of the greater trochanter and the BMC of the neck and
      the minimum neck diameter, but again, the standard error of the estimate is too
      wide to be of much use. In addition, the square of the correlation coefficient
      (R2) is very low, for example, below 0.1 in all cases. Thus, there is very little
      variability in weight that can be accounted for with these variables. DXA
      technology offers the potential of a living skeletal data bank and of variables
      that are useful in cause-effect relationships between bone mineralization and
      skeletal loads.

PMID- 15567619
TI  - Discriminant function sexing of fragmentary and complete tibiae from medieval
      Croatian sites.
AB  - Previous studies have demonstrated that populations differ from each other in
      size and proportion and that these differences can affect metric assessment of
      sex. This paper establishes standards for determining sex from fragmentary and
      complete tibiae in the medieval Croatian population. The sample is composed of
      180 tibiae (96 males and 84 females) from six medieval archaeological sites in
      Croatia. Three of the sites were located in continental Croatia, three on the
      eastern Adriatic coast and its immediate hinterland. Six tibial dimensions were
      measured: (1) length of the tibia; (2) maximum epiphyseal breadth of the proximal
      tibia; (3) maximum epiphyseal breadth of the distal tibia; (4) maximum diameter
      of the tibia at the nutritient foramen; (5) transverse diameter of the tibia at
      the nutritient foramen; and (6) circumference of the tibia at the nutritient
      foramen. Unifactorial and multifactorial analyses were performed on the collected
      data. Six discriminant functions were generated, one using six variables, two
      using two variables, and three employing one variable. Results show that complete
      tibiae can be sexed with 92.2% accuracy. Slightly lower accuracies (91.7 and
      87.8%) were achieved using a combination of two variables, while functions
      employing one variable were accurate from 85.6 to 81.7%. The results of this
      study show that the medieval Croatian tibia is a good skeletal component for
      determining sex. Standardized coefficients of the discriminant functions
      generated in this study support the results of previous studies that found that
      breadth dimensions provide better separation of the sexes than length.

PMID- 15567620
TI  - Metric determination of sex from the humerus in a Guatemalan forensic sample.
AB  - The absence of population-specific standards for sex, age and stature estimation
      for rural Guatemala is problematic for the forensic analysis of skeletal remains
      recovered from clandestine graves attributed to the recent armed conflict in that
      country. In order to increase the reliability of the forensic analyses being
      undertaken in Guatemala, standards for metric determination of sex were
      developed. Data was collected on several bones; the results for the humerus are
      presented here. A sample of 118 complete humeri (68 male and 50 female) was
      studied; maximum length, maximum diameter of the head, circumference at midshaft,
      maximum diameter at midshaft, minimum diameter at midshaft and epicondylar
      breadth were measured and subjected to discriminant function analysis. The
      classification accuracies for the univariate functions range from 76.8% for the
      maximum diameter at midshaft to 95.5% for the maximum diameter of the head. The
      classification accuracy for the stepwise procedure was 98.2%.

PMID- 15567621
TI  - The reliability of sex determination of skeletons from forensic context in the
      Balkans.
AB  - In this study we have tested the applicability of morphological methods for sex
      assessment, based on seven pelvic and nine cranial traits, using contemporary
      Balkans population. The material involved in the study comprises 262 pelvic bones
      and 180 skulls of male individuals from two mass graves in Serbia. The material
      was examined separately by an experienced and an inexperienced physical
      anthropologists. Sex was correctly estimated by the experienced anthropologist in
      100% of individuals using all of the 16 pelvic and cranial criteria. In fact, sex
      differences in pelvic morphology were large enough to allow sexing the
      individuals with 100% accuracy. Among seven features observed on the pelvic
      bones, the least reliable single sex indicator was the width of the great sciatic
      notch (with accuracy of 79.15%). Looking at the skull alone, sex was correctly
      determined in 70.56% cases. It was shown that the most accurate single indicators
      among cranial methods was the robustness of the mandible (with accuracy of
      70.93%), while the sharpness of the supraorbital margins was the least reliable
      indicator demonstrating accuracy in only 28.75% of crania. Examination of the
      sample by an individual with training in physical anthropology, but no case
      experience, suggests that experience is likely to contribute moderately to the
      accuracy of the sex determination. Namely, the inexperienced anthropologist
      accurately assessed the sex of the sample 95.04% of the time; 4.06% less accurate
      than the experienced anthropologist. The two anthropologists showed the least
      agreement in scoring the ventral arc and composite arc on the pelvic bones.

PMID- 15567622
TI  - Ilium growth study: applicability in sex and age diagnosis.
AB  - The use of coxal elements for age and sex diagnosis from the skeleton is the
      primary and most widespread way of bringing us closer to the identity of dead
      individuals in archaeological and certain forensic scenarios. Diagnosis in sub
      adults, especially in fetus and infant age, is not clear; and further studies are
      needed. This work presents the analysis of the growth of six variables in the
      ilium, from birth to 97 years of age, in order to evaluate its significance and
      its capacity for age and sex determination during and after growth. The materials
      used were 327 specimens from four documented Western European collections. Growth
      curves were calculated for the three classical variables of the ilium (width,
      length and index) and three new variables of the acetabulum area (horizontal and
      vertical diameter of the ilium acetabular surface and the ilium acetabular
      index). None of the curves showed a lineal growth, except those of the horizontal
      diameter of the ilium acetabular surface for the male series. The ilium width has
      the most complicated growth and it is explained by a four-degree polynomial. All
      the variables studied can be useful for adult sex discrimination with the
      exception of the ilium width and ilium acetabular index. Furthermore, the most
      useful variables for subadult and adult age estimation in archaeological samples,
      as well as in forensic samples, are the absolute measurements (ilium length and
      width, horizontal and vertical diameter of the ilium acetabular surface);
      however, the ilium width is the best variable, as this can be applied to all
      growth ages using both sexual series together up to 20 years of age.

PMID- 15567623
TI  - Determination of sex by discriminant function analysis and stature by regression
      analysis: a lateral cephalometric study.
AB  - Determination of sex and estimation of stature from the skeleton is vital to
      medicolegal investigations. In the present study, an attempt is made to determine
      sex and estimate stature of an individual using data derived from lateral
      cephalogram in Central Indian population. Skull is composed of hard tissue and is
      the best preserved part of skeleton after death, hence, in many cases it is the
      only available part for forensic examination. Lateral cephalogram is ideal for
      the skull examination as it gives details of various anatomical points in a
      single radiograph, also it easily provides architectural and morphological
      details of skull superstructures and intra-cranial details for comparisons. A
      discriminant function derived from 10 cephalometric variables provided 99%
      reliability in sex determination. The formulae obtained from regression analysis
      using the maximum length of skull showed very high degree of reliability for
      estimation of stature in males as well as females.

PMID- 15567624
TI  - Stature and sex estimate using foot and shoe dimensions.
AB  - The aim of the study was to develop a formula to estimate the stature and sex of
      an individual using foot and shoe dimensions. To this aim the stature, right and
      left shoe sizes, and maximum and minimum feet length and width measurements of a
      target group of 569 individuals were taken. The group was composed of 294 males
      and 275 females. The highest correlation coefficient was found in length
      measurements. A notable difference between males and females existed with regard
      to both right and left foot and shoe length and width averages and shoe sizes (p
      < 0.001). Among the group, a significant correlation was found in regard to
      stature and right shoe length (r = 0.591, p < 0.001), with the correlation
      between stature and right foot length and stature and right shoe length being
      0.579 (p < 0.001); as for the female group, there was a significant correlation
      between stature and right foot length and stature and right shoe length (r =
      0.460, p < 0.001). Thus the regression formula obtained are as follows: for the
      right side: sex = 69.169 + 0.173 (maximum foot length) - 0.368 (maximum foot
      width) - 0.820 (shoe length) + 0.224 (shoe width) - 1.280 (shoe number). For the
      left side: sex = 69.551 + 0.276 (maximum foot length) - 0.504 (maximum foot
      width) - 0.739 (shoe length) + 0.344 (shoe width) - 1.360 (shoe number). In
      application of the formula, if sex is lower than 0.50, the shoe belongs to a
      male, if higher, then to female. The formula which was obtained in regression
      analysis in order to estimate the stature when the measurements of shoe and foot
      were known. For the right side, stature = 47.93 + 1.083 (maximum foot length) +
      0.788 (shoe length) 1.813 (shoe number) (SEE:31.410). For the left side: stature
      = 47.33 + 1.139 (maximum foot length) + 0.593 (shoe length) x 1.924 (shoe number)
      (SEE:31.607). It was understood that foot and shoe sizes are a criteria to
      estimate the stature of a person that there was a strong relationship between
      foot and shoe length and width and that these can be used to aid estimation. It
      was found that in sex estimate, foot and shoe lengths are better in helping the
      estimate than width measurements, and that the use of shoe measurements rather
      than bare foot measurements are better to obtain meaningful results.

PMID- 15567625
TI  - The estimation of stature on the basis of measurements of the femur.
AB  - The study aims to establish the relationship between body height and the greatest
      length of the femur. The motive for undertaking these examinations was the lack
      in the literature of studies that allow -- with reference to the current
      population of Central Europe -- the reconstruction of height while alive based on
      measurements of a skeleton. It was decided to examine isolated bones from human
      remains undergoing forensic autopsy, and belonging to individuals of both sexes
      whose growth processes had stopped. Examinations were conducted on 91 human
      bodies from the contemporary Polish population. The research points to a very
      close relationship between the length of a dead body and the measured greatest
      length of the femur. This relationship was expressed in nine coefficients of
      correlation calculated for both sexes.

PMID- 15567626
TI  - The diagnostic randomized clinical trial is the best solution for management
      issues in critical limb ischemia.
AB  - OBJECTIVE: The value of a new diagnostic test is usually established by analyzing
      its accuracy in relation to a reference standard. Here we describe a potentially
      better model of diagnostic research, namely, a diagnostic randomized clinical
      trial (D-RCT), and discuss its pros and cons using management of critical limb
      ischemia as an example. STUDY DESIGN AND SETTING: Patients clinically suspected
      of critical limb ischemia are randomized either for the conventional management
      strategy (treating physician determines the diagnostic and therapeutic strategy
      on clinical judgment and ankle pressure) or new strategy (transcutaneous oxygen
      and toe pressure determine the diagnostic and therapeutic strategy). The effect
      of the diagnostic work-up on the diagnostic and therapeutic process and clinical
      outcome will be evaluated. RESULTS: A D-RCT is suited when a true reference
      standard is lacking. It is the best available research method to control for
      confounding and bias, and it also incorporates the total effect (interpretation
      and side effects) on clinical outcome. The D-RCT has some disadvantages, however,
      as to the power and size of the trial and the influence of treatment on the
      outcome parameter. CONCLUSIONS: A D-RCT can provide valuable information as to
      the evaluation of diagnostic tests.

PMID- 15567627
TI  - Block design allowed for control of the Hawthorne effect in a randomized
      controlled trial of test ordering.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the value of balanced incomplete block
      designs in quality improvement research, and their capacity to control for the
      Hawthorne effect. METHODS: General practitioners teams were randomized into three
      arms and received an intervention on test ordering, relating to tests for two
      groups of clinical problems (A tests and B tests). In the two trials within the
      block design, we tried to control for the Hawthorne effect by comparing the
      complete intervention in both arms on either the A (arm I) or B tests (arm II);
      the arms acted as blind controls for each other. In the classical trial, the
      complete intervention on B tests (arm II) was compared with a control arm without
      any intervention on B tests (arm III). RESULTS: The trials with the block design
      yielded statistically significant changes in the numbers of A tests ordered
      (P=.013), but not in the numbers of B tests ordered (P=.29). In the classical
      design, the complete intervention reached a marginally significant change in the
      B tests (P=.068). The Hawthorne effect was the same for both arms of the block
      design. In the classical design, the effect could to some extent be attributed to
      the Hawthorne effect. CONCLUSION: Our block design allowed us to control for the
      Hawthorne effect. Suitable use of block designs may further our knowledge of
      nonspecific effects in quality improvement research.

PMID- 15567628
TI  - In a randomized controlled trial, missing data led to biased results regarding
      anxiety.
AB  - BACKGROUND AND OBJECTIVE: Randomization does not protect against bias due to
      missing observations. In addition, different reasons for missing observations may
      lead to different invalid results. The purpose of this study was to illustrate
      how randomized intervention studies can be threatened by bias due to missing
      observations because of death or nonresponse. METHODS: A randomized clinical
      trial of the effect of psychosocial intervention on well-being after an operation
      for colorectal cancer was conducted in Denmark. Patients were interviewed 3, 6,
      12, and 24 months after discharge from hospital. RESULTS: We found that the
      probability of nonresponse decreased with increasing anxiety score in the
      intervention group, but it increased with increasing anxiety score in the control
      group. This could lead to severe bias in an analysis of the effect of
      intervention on anxiety. Low physical functioning and low global health status
      and quality of life were related to an increased probability of dying before the
      next follow-up, and this association could explain the associations between
      anxiety and depression, respectively, and the probability of dying observed in
      crude analyses. CONCLUSION: Our study emphasizes the importance of performing
      specific missing data analyses in any study of well-being variables.

PMID- 15567629
TI  - Automated variable selection methods for logistic regression produced unstable
      models for predicting acute myocardial infarction mortality.
AB  - OBJECTIVES: Automated variable selection methods are frequently used to determine
      the independent predictors of an outcome. The objective of this study was to
      determine the reproducibility of logistic regression models developed using
      automated variable selection methods. STUDY DESIGN AND SETTING: An initial set of
      29 candidate variables were considered for predicting mortality after acute
      myocardial infarction (AMI). We drew 1,000 bootstrap samples from a dataset
      consisting of 4,911 patients admitted to hospital with an AMI. Using each
      bootstrap sample, logistic regression models predicting 30-day mortality were
      obtained using backward elimination, forward selection, and stepwise selection.
      The agreement between the different model selection methods and the agreement
      across the 1,000 bootstrap samples were compared. RESULTS: Using 1,000 bootstrap
      samples, backward elimination identified 940 unique models for predicting
      mortality. Similar results were obtained for forward and stepwise selection.
      Three variables were identified as independent predictors of mortality among all
      bootstrap samples. Over half the candidate prognostic variables were identified
      as independent predictors in less than half of the bootstrap samples. CONCLUSION:
      Automated variable selection methods result in models that are unstable and not
      reproducible. The variables selected as independent predictors are sensitive to
      random fluctuations in the data.

PMID- 15567630
TI  - A review of two journals found that articles using multivariable logistic
      regression frequently did not report commonly recommended assumptions.
AB  - BACKGROUND AND OBJECTIVE: To examine if commonly recommended assumptions for
      multivariable logistic regression are addressed in two major epidemiological
      journals. METHODS: Ninety-nine articles from the Journal of Clinical Epidemiology
      and the American Journal of Epidemiology were surveyed for 10 criteria: six
      dealing with computation and four with reporting multivariable logistic
      regression results. RESULTS: Three of the 10 criteria were addressed in 50% or
      more of the articles. Statistical significance testing or confidence intervals
      were reported in all articles. Methods for selecting independent variables were
      described in 82%, and specific procedures used to generate the models were
      discussed in 65%. Fewer than 50% of the articles indicated if interactions were
      tested or met the recommended events per independent variable ratio of 10:1.
      Fewer than 20% of the articles described conformity to a linear gradient,
      examined collinearity, reported information on validation procedures, goodness-of
      fit, discrimination statistics, or provided complete information on variable
      coding. There was no significant difference (P>.05) in the proportion of articles
      meeting the criteria across the two journals. CONCLUSION: Articles reviewed
      frequently did not report commonly recommended assumptions for using
      multivariable logistic regression.

PMID- 15567631
TI  - An integrated method to determine meaningful changes in health-related quality of
      life.
AB  - OBJECTIVE: We describe an integrated method for determining meaningful change in
      health-related quality of life (HRQOL) that combines information from anchor
      based and distribution-based methods and illustrate this method using data
      aggregated from weight loss studies. STUDY DESIGN AND SETTING: A total of 1476
      participants in weight loss studies were evaluated at baseline and at 6 months
      using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite). Severity of
      baseline impairment was determined by comparing scores with those obtained from a
      normative sample of 534 normal/overweight individuals. The precision of the IWQOL
      Lite was evaluated using standard error of measurement corrected for regression
      to the mean. Weight loss was used as an anchor for evaluating changes in IWQOL
      Lite scores. RESULTS: Change in HRQOL varied as a function of weight loss and
      baseline severity of HRQOL. Using this integrated method, an improvement of 7.7
      to 12 points (depending on baseline severity) on IWQOL-Lite total score is
      considered meaningful. CONCLUSION: Meaningful change in HRQOL can be determined
      using an integrated method that (1) combines information from anchor-based and
      distribution-based methods, (2) reconciles discrepancies between these two
      methods, and (3) adjusts for baseline severity and regression to the mean. This
      method may be applied to other types of HRQOL measures and conditions.

PMID- 15567632
TI  - Health-related quality of life (HRQL) scores reported from parents and their
      children with chronic illness differed depending on utility elicitation method.
AB  - OBJECTIVE: To describe the relationship between health-related quality of life
      (HRQL) as measured by utility when elicited from parents and their children with
      chronic illness. STUDY DESIGN AND SETTING: We enrolled families of children
      admitted for cancer chemotherapy and those attending outpatient rheumatology,
      hemophilia and bone marrow transplantation clinics. Children in grade 6 or higher
      were included. The child's HRQL was rated by parent and child using the Standard
      Gamble (SG), Visual Analogue Scale (VAS), Time Trade-Off (TTO), and Health
      Utilities Index Mark 2/3 (HUI2 and HUI3). RESULTS: 22 families were included. The
      mean parent SG was 0.92 +/- 0.09, which was similar to the mean SG elicited from
      their children of 0.92 +/- 0.10. The parent and child SG were moderately
      concordant (ICC=0.64, 95% CI=0.30, 0.83; P=.0005). In contrast, TTO scores were
      not concordant (ICC=0.14, 95% CI=-0.29, 0.53; P=.3), with parents (mean TTO=0.77
      +/- 0.31) rating HRQL worse than children (mean TTO=0.92 +/- 0.11; P=.04).
      Similarly, the mean parent HUI2 of 0.82 +/- 0.22 was lower than the child HUI2 of
      0.95 +/- 0.07; P=.02 and HUI2 were not concordant (ICC=0.11, 95% CI=-0.35, 0.53;
      P=.3) between parents and children. CONCLUSION: Parents and children rate HRQL
      similarly according to SG, but parents rate HRQL significantly worse using TTO
      and HUI2.

PMID- 15567633
TI  - Mode of delivery, but not questionnaire length, affected response in an
      epidemiological study of eating-disordered behavior.
AB  - BACKGROUND AND OBJECTIVES: The effects of questionnaire length and mode of
      delivery on response rates were examined in an epidemiological study of eating
      disordered behavior. METHODS: Short (8 pages) and long (14 pages) questionnaires
      were posted or hand-delivered to a community sample of 802 women. Nonrespondents
      who received the first questionnaire by hand delivery received a reminder letter
      and replacement questionnaire by post; those who received the initial
      questionnaire by post were further randomized to receive the first reminder by
      hand delivery or by post, in short or long form. A second reminder letter and
      questionnaire (in short or long form) were posted to all remaining
      nonrespondents. RESULTS: The overall response rate was 52.9%. This is a
      conservative estimate of true response, because in a substantial proportion of
      cases (12.2%) individuals were no longer resident at the listed address. There
      was a significant effect of mode of delivery on response, favoring hand delivery,
      at both the initial mailout and first reminder. There was no effect of
      questionnaire length on response to the initial mailout, although overall
      response was significantly higher for the longer form. It was estimated that an
      overall response of 58.0% would have been achieved had first reminders been hand
      delivered to all nonrespondents who received the initial mailout by post.
      CONCLUSIONS: Delivery of questionnaires by hand may be an effective way to
      increase response rates in epidemiological research, but little is to be gained
      by reducing questionnaire length.

PMID- 15567634
TI  - Active recruitment increased enrollment in a hereditary cancer registry.
AB  - BACKGROUND AND OBJECTIVE: The Mid-Atlantic Cancer Genetics Network (MACGN)
      targets individuals from cancer risk assessment clinics for recruitment into a
      national hereditary cancer registry. We sought to determine whether different
      recruitment methods used in a high-risk breast and ovarian cancer clinic yielded
      differences into enrollment into MACGN. METHODS: Two methods of recruitment were
      compared over an 8-month period. A passive recruitment technique, used during the
      first 4 months of recruitment, involved distribution of a brochure. An active
      recruitment method, used during the second 4-month period, required a MACGN
      recruiter to approach patients and initiate a brief discussion of the registry.
      RESULTS: During the first 4-month period, 158 eight patients were seen in the
      clinic and 142 were seen in the second 4-month period. During passive
      recruitment, 20% of available patients were approached, compared with 63% during
      active recruitment. Active recruitment also resulted in fourfold increase over
      passive recruitment in enrollment (from 15.6% to 67.4%). CONCLUSION: Allocating
      research staff specifically for recruitment and personal contact with potential
      participants is effective in achieving increased enrollment into a national
      hereditary cancer research registry.

PMID- 15567635
TI  - Asthma severity scores for preschoolers displayed weaknesses in reliability,
      validity, and responsiveness.
AB  - OBJECTIVE: To evaluate the measurement properties of asthma severity scores for
      use in preschool children. METHODS: A Medline search was used to identify
      published asthma severity scores for use in preschool children. The measurement
      properties of the scores (item development, reliability, validity,
      responsiveness, and usability) were evaluated using a published framework.
      RESULTS: Ten asthma severity scores were identified, with 19 different clinical
      variables used as items. Interrater agreement was assessed by five scores. Only
      two scores--Clinical Asthma Score (CAS) and Respiratory Distress Assessment Index
      (RDAI)--reported good agreement based on weighted kappa-statistics (0.64-0.90).
      Construct validity was reported by the CAS, Clinical Asthma Evaluation Score
      (CAES), the Clinical Symptom Grading System (CSGS), and the Preschool Respiratory
      Assessment Measure (PRAM). Correlation coefficients between asthma severity
      scores and clinical measures (length of stay, drug dosing interval, O2
      saturation, health professional assessment, PaO2, PaCO2) ranged from 0.47 to
      0.70. Responsiveness was formally demonstrated for two scales (PRAM, CAS).
      CONCLUSIONS: Most asthma severity scales for use in preschool children have been
      informally developed. Recently developed scores (CAS, PRAM) have more rigorously
      evaluated their measurement properties. Research is needed to directly compare
      the asthma severity scores developed for use in preschool children.

PMID- 15567636
TI  - Most severe neutropenia in individuals with no chronic condition did not result
      in a specific diagnosis.
AB  - BACKGROUND AND OBJECTIVES: This study estimated the incidence of unexplained
      severe neutropenia (neutrophil count 500 x 10(6)/L) and hospitalized morbidity in
      the year after a finding of severe neutropenia in persons 2 years of age or older
      based on clinical laboratory data. METHODS: Computer-stored data from the Kaiser
      Permanente Laboratory Management System/Results Management System were used to
      identify findings of severe neutropenia in members of Kaiser Permanente Southern
      California 2 years of age or older during the period January 1, 1997, through
      December 31, 1999. Computer record linkage and medical record review were used to
      exclude individuals with chronic disease or treatments with bone marrow toxic
      drugs known to cause neutropenia. RESULTS: The incidence of findings of severe
      neutropenia was 47 per million persons per year (95% CI=42-53). Only 11% of
      individuals with a finding of severe neutropenia were hospitalized with
      neutropenia diagnosis. The hospitalization rate for infection occurring within 1
      year of severe neutropenia was 3.2% (95% CI=1.5-6.2%). CONCLUSION: Most
      laboratory findings of severe neutropenia in individuals with no chronic
      condition do not result in a specific diagnosis. In a population-based sample of
      findings of severe neutropenia identified by laboratory testing, hospitalization
      for infection was rare.

PMID- 15567637
TI  - Patients with type 2 diabetes had higher rates of hospitalization than the
      general population.
AB  - OBJECTIVE: We describe the rate, causes, and predictors of hospitalization for
      all patients with type 2 diabetes in a diabetes clinic in Turin, Italy and
      compare their hospitalization rates with those of the general population. STUDY
      DESIGN AND SETTING: All patients were recruited and followed up for hospital
      admissions from January 1996 to June 2000. The role of risk factors was analyzed
      with a conditional proportional hazard model for repeated events. RESULTS: More
      than 50% of the patients had been admitted to hospital at least once for any
      cause, and 30% had had multiple admissions, accounting for nearly 90% of all days
      in hospital. For these patients, older age, high glycated hemoglobin level,
      obesity, insulin treatment, presence of nephropathy, coronary and peripheral
      artery disease and comorbidity were statistically independent predictors of
      hospital admission. The standardized hospital admission ratios were 158.8 for men
      <65 years of age and 113.3 for men > or = 65 years and 245.2 for women <65 years
      of age and 135.3 for women > or = 65 years of age. The highest ratios were for
      diabetes, vascular (cardiac and cerebral) diseases, and eye diseases in younger
      women. CONCLUSION: Patients with type 2 diabetes, and particularly younger women,
      had higher rates of hospitalization than the general population, with an excess
      risk of about 30%.

PMID- 15567638
TI  - A population survey found an association between self-reports of traumatic brain
      injury and increased psychiatric symptoms.
AB  - OBJECTIVE: This study determined whether self-reported Traumatic Brain Injury
      (TBI), identified in a community sample and occurring up to 60 years previously,
      is associated with current psychiatric symptoms, suicidality, and psychologic
      well-being. STUDY DESIGN AND SETTING: Three age cohorts (20-24, 40-44, 60-64)
      were randomly sampled from the cities of Canberra and Queanbeyan, Australia,
      yielding a total of 7,485 participants. The samples were administered scales
      measuring anxiety, depression, suicidality, positive and negative affect,
      personality traits, and physical health status. RESULTS: Of the total sample,
      5.7% reported history of TBI involving loss of consciousness for at least 15 min,
      occurring an average of 22 years previously. History of TBI was associated with
      increased symptoms of depression, anxiety, negative affect, and suicidal
      ideation. CONCLUSION: History of TBI is a risk factor for psychiatric morbidity.
      The effect is greatest in young adults, and occurs up to several decades
      subsequent to the occurrence of TBI.

PMID- 15567639
TI  - An interview strategy was critical for obtaining valid information on the use of
      hormone replacement therapy.
AB  - OBJECTIVE: We compared telephone reports of hormone replacement therapy (HRT) use
      to claims for drugs dispensed. STUDY DESIGN AND SETTING: The study subjects
      included 106 women who were dispensed HRT and 107 who were not dispensed HRT.
      RESULTS: Recall of drug use overall was relatively good (65/79=82.3%, 95%
      confidence interval [CI] 73.9-90.7). Agreement between recall of drug name and
      the claims for dispensed drugs was lower (61/79=77.2%, 95% CI 68.0-86.5). Of 65
      women reporting use of HRT in response to the indication prompt, nine (13.8%)
      could not identify the drug name using the drug list prompt, but all 65 women
      identified a drug using the photo prompt. Recall of start date of drug use was
      poor (29.2% agreement on month/year; 45.8% agreement within 1 month), and recall
      of end date of drug use was poorer yet (7.7% agreement on month/year; 21.5%
      agreement within 1 month). CONCLUSION: Recall of drug use and drug names is far
      better than recall of dates of use. Recall can be enhanced with lists of drug
      names and color photos, but even with memory prompts, recall remains imperfect.
      If drug use is the primary exposure of interest in a study, considerable effort
      is needed to collect it correctly. If not, then perhaps drug histories should be
      omitted.

PMID- 15567640
TI  - Two measures of insulin sensitivity provided similar information in a U.S.
      population.
AB  - BACKGROUND AND OBJECTIVE: Two methods for measuring insulin sensitivity, fasting
      plasma insulin (FPI) and homeostasis model assessment (HOMA) have been proposed
      for use in large epidemiological research and clinical practice. This project
      describes the range of observed values of the HOMA and FPI in a large sample of
      the U.S. population. METHODS: We used fasting plasma glucose and insulin values
      from the Third National Health and Nutrition Survey (NHANES III) to identify the
      FPI and HOMA values. For both FPI and HOMA, higher values indicate lower insulin
      sensitivity. RESULTS: Among 6,511 participants without treated diabetes mellitus,
      FPI ranged from 1.8 to 175.8 microU/mL, with 25th percentile=6.7, median=9.3,
      75th percentile=13.3, and mean+/-1 SD=11.2+/-7.5; HOMA ranged from 0.3 to 52.6
      (mmol)(microU)/L(2), with 25th percentile=1.5, median=2.2, 75th percentile=3.3,
      and mean+/-SD=2.8+/-2.4. CONCLUSION: These findings describe the spectrum of
      insulin sensitivity and may be useful in helping physicians develop a clinical
      understanding of the dynamic range of both FPI and HOMA measures.

PMID- 15567641
TI  - The postoperative analgesic efficacy of wound instillation with ropivacaine 0.1%
      versus ropivacaine 0.2%.
AB  - STUDY OBJECTIVES: To assess the influence of ropivacaine concentration on wound
      instillation-induced postoperative analgesia following total abdominal
      hysterectomy with bilateral salpingo-oophorectomy. DESIGN: Prospective,
      randomized, double-blind study. SETTING: Large referral hospital. PATIENTS: 40
      ASA physical status I and II patients undergoing total abdominal hysterectomy
      with bilateral salpingo-oophorectomy. INTERVENTIONS: A standard general
      anesthetic was administered. In all cases surgery was performed via a
      Pfannenstiel incision. On completion of the surgery, a multi-orifice, 20-gauge
      epidural catheter was placed above the fascia such that the tip was sited at the
      point that demarcated 50% of the length of the surgical wound. Thereafter, the
      catheter was connected to an electronic patient-controlled analgesia (PCA) device
      programmed to deliver 9 mL of drug, with a lockout time of 60 minutes and no
      basal infusion. Patients were randomized to receive PCA with ropivacaine 0.1%
      (Group 0.1) or ropivacaine 0.2% (Group 0.2). During the first 6 postoperative
      hours, a co-investigator administered "rescue" morphine (2 mg IV). Thereafter,
      "rescue" meperidine 1 mg/kg was administered on patient request. MEASUREMENTS AND
      MAIN RESULTS: The number of attempts to activate the PCA device and actual PCA
      instillations during the 24 hour study period were similar between the groups.
      The number of 2 mg "rescue" morphine dosages administered was 4.3 +/- 1.7 versus
      4.4 +/- 2.5 for the Group 0.1 and Group 0.2, respectively. For Group 0.1 and
      Group 0.2, the total dose of "rescue" morphine administered during the first 6
      postoperative hours was 8.7 mg +/- 3.6 versus 9.1 mg +/- 5, respectively.
      "Rescue" meperidine administration during the subsequent 18 hours was similar
      between the groups. Throughout the study period, pain scores were similar between
      the groups. CONCLUSION: With a pre-set volume, varying the concentration of
      ropivacaine (0.1% versus 0.2%) does not affect the analgesic efficacy of wound
      instillation following total abdominal hysterectomy with bilateral salpingo
      oophorectomy.

PMID- 15567642
TI  - A comparison of anesthetic quality in propofol-spinal anesthesia and propofol
      fentanyl anesthesia for total knee arthroplasty in elderly patients.
AB  - STUDY OBJECTIVE: To compare propofol plus spinal anesthesia during spontaneous
      ventilation using the Laryngeal Mask Airway and propofol plus fentanyl anesthesia
      during mechanical ventilation with an endotracheal tube on quality of recovery
      after anesthesia. DESIGN: Prospective, randomized study. SETTING: Hirosaki
      National Hospital. PATIENTS: 150 patients (aged > 70 years) undergoing total knee
      arthroplasty. INTERVENTIONS: Patients were divided randomly into two groups, to
      receive spontaneous ventilation with a Laryngeal Mask Airway during propofol
      spinal anesthesia, or to receive propofol-fentanyl anesthesia with mechanical
      ventilation via endotracheal tube. MEASUREMENTS: Quality of anesthesia recovery
      such as nausea, vomiting, headache, pain throat, hoarse voice, back pain,
      dizziness, feeling comfortable, dreaming, recovery times in recovery of
      anesthesia, recovery times, postoperative pain, confusion, was assessed. MAIN
      RESULTS: The frequency of postoperative pain throat, hoarse voice, and nausea was
      significantly lower in the propofol-spinal anesthesia group than the propofol
      fentanyl anesthesia group. The time to extubation, emergence, response to
      commands, and orientation were significantly faster (p < 0.001) in the propofol
      spinal anesthesia group than the propofol-fentanyl anesthesia group. The
      frequency of postoperative confusion occurring in the propofol-spinal anesthesia
      group during the first 24 hours was significantly lower than that of the propofol
      fentanyl anesthesia group (p = 0.03). CONCLUSIONS: Propofol-spinal anesthesia
      provided better and faster recovery than did propofol-fentanyl anesthesia for
      elderly patients undergoing total knee arthroplasty.

PMID- 15567643
TI  - Induction of labor with oxytocin increases cesarean section rate as compared with
      oxytocin for augmentation of spontaneous labor in nulliparous parturients
      controlled for lumbar epidural analgesia.
AB  - STUDY OBJECTIVES: To study labor outcomes in parturients receiving oxytocin for
      augmentation or induction of labor, in the presence of labor epidural analgesia.
      DESIGN: Retrospective study of data from a continuous quality improvement
      database. SETTING: Tertiary-care hospital with more than 8000 deliveries per
      annum. MEASUREMENTS AND MAIN RESULTS: Of the 1671 healthy nulliparous women with
      singleton pregnancies and who requested labor epidural analgesia at our
      institution, 675 patients received oxytocin during elective induction of labor,
      whereas 996 patients received oxytocin for augmentation of spontaneous labor.
      Measured variables were cervical dilatation at time of epidural analgesia
      request, epidural insertion to 10-cm time, duration of stage 2 of labor, normal
      spontaneous vaginal delivery rate, cesarean section rate, operative vaginal
      delivery rate, and baby weight. Women admitted for induction of labor requested
      epidural analgesia sooner than those who had their labor augmented (p < 0.001).
      The incidence of cesarean section was higher in the induced group (p = 0.008).
      CONCLUSION: Patients who have their labor induced request analgesia sooner and
      are at a higher risk of cesarean section than are patients who go into labor
      spontaneously. Any study that purports to assess the effects of epidural
      analgesia in labor should distinguish between induced and augmented/spontaneous
      labor.

PMID- 15567644
TI  - Establishing a nurse-based, anesthesiologist-supervised inpatient acute pain
      service: experience of 4,617 patients.
AB  - STUDY OBJECTIVE: To describe our nurse-based Acute Pain Services (APS) and
      present the results of 4617 patients treated by our service. DESIGN: Descriptive
      audit. SETTING: Large referral hospital. PATIENTS: 4617 patients treated by the
      APS. MEASUREMENT AND MAIN RESULTS: Analgesic regimens [basic pain treatment,
      patient-controlled analgesia (PCA), epidural analgesia, spinal analgesia, and
      wound instillation], as well as the associated patient monitoring and event
      response algorithms are detailed. The mean visual analog score (VAS) for pain was
      low. A VAS for pain greater than 30 mm was noted in 15.3% of all pain scores
      recorded. Bradypnea (respiratory rate < 10 breaths/min) was recorded in 19
      patients (overall incidence = 0.4%). No complications resulting in sustained
      morbidity or mortality occurred. Of the patients, 96% described their overall
      satisfaction with the APS as either good or excellent. CONCLUSION: A nurse-based
      APS provides effective and safe postoperative pain management.

PMID- 15567645
TI  - Using length of stay data from a hospital to evaluate whether limiting elective
      surgery at the hospital is an inappropriate decision.
AB  - STUDY OBJECTIVE: At hospitals without detailed managerial accounting data but
      with overall longer than average diagnosis-related groups (DRG)-adjusted lengths
      of stays (LOS), some administrators do not aggressively hire the nurses needed to
      maintain surgical hospital capacity. The consequence of this (long-term) decision
      is that day-of-surgery admit cases are delayed or cancelled from a lack of beds.
      The anesthesiologists suffer financially. In this paper, we show how publicly
      released national LOS data can be applied specifically to these cases. DESIGN: We
      applied the method to 1 year of data from two academic hospitals. Each case's LOS
      was compared to the United States national average LOS for cases with the same
      DRG. MEASUREMENTS AND MAIN RESULTS: A total of 8,050 and 10,099 hospitalizations,
      respectively. Among all surgical admissions, mean LOS was 2.5 days longer than
      the national average for Hospital #1 (95% confidence interval [CI], 2.1 to 2.8)
      and 3.1 days longer for Hospital #2 (95% CI, 2.8 to 3.4). Among patients
      undergoing elective, scheduled surgery with day of surgery admission, mean LOS
      was 0.7 days less than average for Hospital #1 (0.6 to 0.9) and 1.2 days less
      than average for Hospital #2 (1.1 to 1.4). CONCLUSIONS: This method can be used
      by anesthesiologists to show that LOS are not longer than average among patients
      whose surgeries may be cancelled or delayed for a lack of hospital ward staff.

PMID- 15567646
TI  - Patient attitudes toward granting consent to participate in perioperative
      randomized clinical trials.
AB  - STUDY OBJECTIVE: To determine the factors that affect patients' decisions to
      provide informed consent to participate in perioperative clinical trials. DESIGN:
      Survey instrument (questionnaire). SETTING: Urban, tertiary-care, university
      affiliated hospital. MEASUREMENTS AND MAIN RESULTS: Of 52 patients who had been
      asked to participate in a randomized control trial (RCT), 43 agreed to be
      participate in our survey. Almost all consenters (97%), but only 62% of
      nonconsenters agreed to answer the survey questions (p = 0.002). No significant
      difference in gender, ethnic background, marital status, or education level was
      found between groups who were or were not willing to participate. Univariate
      correlates of agreement to participate in RCTs included older age (>60 yrs;p =
      0.02), a reassuring attitude conveyed by study personnel (p = 0.02), and trust in
      study personnel (p = 0.02). Those who declined participation in clinical trials
      more frequently indicated that the study made them feel like a "guinea pig" (p =
      0.02). CONCLUSION: Patient age and personal attitudes predict the likelihood of
      participation in perioperative clinical trials. Neither gender nor race affected
      willingness to participate. Further work in larger groups is needed to identify
      predictors of consent and techniques to increase willing participation.

PMID- 15567647
TI  - Vascular endothelial growth factor (VEGF) in plasma increases after hip surgery.
AB  - STUDY OBJECTIVE: To determine whether the plasma concentration of vascular
      endothelial growth factor (VEGF) is elevated after a common surgical procedure,
      and if any increase is followed by a reduction in the amount of infused
      crystalloid fluid in the blood. DESIGN: Nonrandomized study. Experimental group
      age-matched to control group. SETTING: Operating room of a large medical research
      center. PATIENTS: 10 ASA physical status I, II, and III patients, aged 51 to 94
      years, scheduled for hip surgery; and 10 ASA physical status I and II volunteers,
      aged 53 to 71 years, comprising a control group. INTERVENTIONS: Patients and
      control subjects were given an intravenous volume load of Ringer's acetate
      solution (12.5 mL/kg for 30 min). MEASUREMENTS: The plasma concentrations of C
      reactive protein, interleukin-6, interleukin-8 (inflammatory parameters used as
      biochemical evidence of trauma), and VEGF were measured in patients the morning
      after the day of the surgery. The area under the curve (AUC) for the plasma
      dilution was calculated in response to the intravenous fluid. MAIN RESULTS: VEGF
      concentration was tripled in the hip group (100.7 +/- 18.5 pg/L vs. 31.9 +/- 7.2
      pg/L; p < 0.001) as a consequence of the trauma of surgery. The other
      inflammatory parameters were also significantly increased. There was no
      difference in AUC between the two groups during infusion, but after infusion AUC
      was significantly increased in the hip group versus controls (4.88 vs. 2.8; p =
      0.025), suggesting persistence of the infused fluid to remain in the vasculature.
      AUC was not highly correlated with any of the inflammatory parameters regardless
      of group during or after infusion. CONCLUSIONS: Intravascular persistence of
      infused crystalloid is increased after hip surgery despite elevated VEGF levels
      in plasma.

PMID- 15567648
TI  - Spinal cord infarction and paraplegia after peripheral vascular surgery with
      spinal anesthesia.
AB  - Paraplegia after peripheral vascular surgery under spinal anesthesia is rare and
      may be a result of multiple factors, including hematoma, trauma from the needle,
      toxic injection, and spinal cord infarction. We report a case of T(10) paraplegia
      after uncomplicated spinal anesthesia in a patient undergoing emergency
      thrombectomy and femoral-popliteal bypass.

PMID- 15567649
TI  - Case report of the one-armed anesthesiology resident.
AB  - A severe limb injury challenges an anesthesiologist's ability to provide care. We
      describe the difficulties encountered by an anesthesiology resident with a
      severely injured left arm and present solutions to overcoming an inability to
      perform traditional direct laryngoscopy. Airway management adjuncts explored
      include modified left-handed direct laryngoscopy, lighted stylet intubation,
      fiberoptic intubation, Laryngeal Mask Airway, Combitube, retrograde wire
      technique, and the eventual conversion to direct laryngoscopy with the right hand
      with the reversed Macintosh and the Cranwall modification of the Miller blade.
      The practical and social problems of a disability during residency are also
      discussed.

PMID- 15567650
TI  - Hyperkalemic cardiac arrest following succinylcholine administration: The use of
      extracorporeal membrane oxygenation in an emergency situation.
AB  - We report an 11-year-old male with undiagnosed myopathy, who developed cardiac
      arrest secondary to severe rhabdomyolysis and hyperkalemia following
      succinylcholine administration. The patient required extracorporeal membrane
      oxygenation support from which he was eventually weaned successfully. He died
      eleven days after the cardiac arrest as a result of apparent ischemic brain
      injury.

PMID- 15567651
TI  - Laser endotracheal tube failure: kinking of the Rusch Lasertubus resulting in
      near-total airway occlusion.
AB  - We report a case in which kinking of the Lasertubus resulted in near-total
      occlusion of the endotracheal tube, which in turn precluded adequate ventilation.
      Although the reporting of kinked endotracheal tubes is not uncommon in the
      anesthesia literature, our case is unique with respect to the physical mechanism
      responsible for tube deformation.

PMID- 15567652
TI  - Anesthetic management of a patient with congenital methemoglobinemia.
AB  - A knowledge of congenital methemoglobinemia is essential to deliver a safe
      anesthetic to this group of patients. We report the case of a 33-year-old patient
      with congenital methemoglobinemia undergoing a gynecological procedure, and
      discuss the anesthetic implications. The etiology, pathophysiology,
      classification, diagnosis, clinical manifestations, anesthetic considerations,
      treatment options, and postoperative management are also discussed.

PMID- 15567653
TI  - Anesthetic and perioperative management of a patient with Bernard-Soulier
      syndrome.
AB  - We describe a patient with Bernard-Soulier syndrome who underwent emergency
      laparotomy for intraabdominal bleeding. Presentation of this recent case
      highlights some of the anesthetic and perioperative implications of the disease.
      Briefly, perioperative and anesthetic management of patients with Bernard-Soulier
      syndrome should include platelet transfusions and choice of appropriate
      anesthetic drugs and techniques. The potential benefit of desmopressin and
      corticosteroids should be considered. Thrombelastography, if available, is also
      useful.

PMID- 15567654
TI  - Severe maternal bradycardia and asystole after combined spinal-epidural labor
      analgesia in a morbidly obese parturient.
AB  - Serious maternal bradycardia and asystole in laboring parturients after combined
      spinal-epidural labor analgesia are rare. We report such a case in a morbidly
      obese laboring parturient after receiving combined spinal-epidural labor
      analgesia. The differential diagnosis, risk factors, potential contributing
      factors, and the successful management of the complications with our positive
      patient outcome are discussed. Even with the low dose of neuraxial drugs commonly
      administered in combined spinal-epidural labor analgesia, this case underscores
      the importance of vigilance, frequent monitoring, proper positioning, and rapid
      resuscitation with escalating doses of ephedrine, atropine, and epinephrine, all
      of which are essential in the presence of bradycardia or asystole in these
      patients.

PMID- 15567655
TI  - Diagnosis of an unsuspected maternal hemorrhage via fetal heart rate tracing.
AB  - Early detection of placental abruption often relies on the observation of vaginal
      bleeding; however, overt bleeding does not always occur. We report the case of an
      unsuspected placental abruption diagnosis that was prompted by an internal fetal
      scalp electrode tracing. The presence of a "normal" fetal heart rate (FHR) of
      approximately 150 beats per minute with poor variability, which matched the
      maternal heart rate (MHR), suggested that the tracing was not of fetal origin. An
      urgent ultrasound examination revealed a fetal demise with a possible concealed
      abruption, proving that the scalp electrode tracing was actually maternal in
      origin. Though reports of transmission of MHR via a deceased fetus are not new,
      it is uncommon for MHR to mimic a normal, reassuring FHR. This report reinforces
      the need for anesthesiologists to be adept at interpreting and integrating FHR
      monitors with maternal monitors prior to initiation of epidural analgesia.

PMID- 15567656
TI  - Folding of the epiglottis - an unusual complication to be recognized after
      laryngoscopic endotracheal intubation.
AB  - We report a case of folding of the epiglottis during endotracheal intubation, an
      unusual complication of intubation. A 36-year-old female patient underwent
      laryngeal microsurgery for a vocal polyp. Following anesthesia induction, an
      endotracheal tube (ID = 6.0 mm, cuffed) was advanced through an intubating
      laryngoscope via the oropharyngeal route. At the beginning of the surgery, the
      otolaryngologist noted that the patient's epiglottis was folded under the view of
      the surgical laryngoscopy. The endotracheal tube was adjusted immediately by
      withdrawing it 0.5 cm with the cuff deflated. Slight edema of the upper ridge of
      the epiglottis was noted. There were no sequelae such as laryngeal spasm or vocal
      cord palsy after the surgery. The "peardrop" phenomenon is suggested as a
      possible cause of this event. Potential adverse outcomes of this unusual
      occurrence are reviewed.

PMID- 15567657
TI  - Resident training in advanced airway management.
AB  - Management of the difficult airway is an essential skill that should be taught
      during an anesthesiology residency. However, only a minority of anesthesiology
      residency programs have formal rotations in advanced airway management. We
      developed a formal advanced airway rotation as an integral part of our residency
      program, consisting of two 1-month rotations during the residency, each with a
      separate focus. While on the advanced airway rotation, the resident
      anesthesiologist is given a set of objectives, a list of required reading, and a
      required number of procedures unique to advanced airway management that they must
      perform during the rotation. We believe that this rotation has been beneficial in
      improving the residents' exposure to advanced airway techniques, and has
      dramatically improved their capabilities in this important aspect of anesthetic
      of anesthetic training. Additionally, the structure of the rotation ensures
      uniformity in the residents' acquisition of advanced airway skills.

PMID- 15567659
TI  - Standard epidural test dose in obstetric anesthesia: it is not obsolete, but has
      a risk/benefit ratio.

PMID- 15567660
TI  - Beyond cancellations: decreased day of surgery delays from a dedicated
      preoperative clinic may provide cost savings.

PMID- 15567661
TI  - "Renewed" interest in the management of municipal solid waste in economically
      developing countries.

PMID- 15567662
TI  - Suitability of shredded tires for use in landfill leachate collection systems.
AB  - The suitability of shredded tires or "tire chips" for use in the leachate
      collection drainage layer of a municipal solid waste landfill was investigated in
      terms of the: (1) compressibility of the tire chips and resulting changes in
      hydraulic conductivity under varying applied loads, and (2) effect of leachate pH
      on the shredded tries compressibility and hydraulic conductivity behavior. A
      constant head hydraulic conductivity apparatus was fabricated to measure the
      hydraulic conductivity of the tire shred sample under different axial strains.
      Further, the fabricated assembly was capable of measuring hydraulic conductivity
      of the sample at various sample locations at a given strain level. One aim of
      this study was to provide supporting information for permission to use tire chips
      as an alternative to crushed stone in the leachate collection system of a
      landfill. Shredded tires from two different sources were used in this study to
      investigate any differences in the sensitivity of the shredding process to
      compressibility and hydraulic conductivity responses under varied applied loads.
      Under applied vertical loads resulting in average vertical stresses of up to 440
      kPa, equivalent to over 50 m of waste, the maximum normal strain recorded in each
      type of tire chip was observed to plateau at a strain level near or slightly
      greater than 0.5. The results of the permeability testing indicated average
      hydraulic conductivity values ranging between 0.67 and 13.4 cm/s under average
      applied normal stresses ranging from approximately 60 to 335 kPa and strain
      increments between 0.3 and 0.5. These results are one to three orders of
      magnitude higher than the hydraulic conductivity typically specified for drainage
      layers in leachate collection systems of 0.01 cm/s. Additional tests were also
      carried out to identify how landfill leachate and varied pH levels may affect the
      compressibility and hydraulic conductivity of the shredded tires. Care should be
      exercised in extending these results to field conditions, as the results
      presented are based on limited experimental testing data and a limited time
      frame.

PMID- 15567663
TI  - Effect of vermiculite addition on compost produced from Korean food wastes.
AB  - To evaluate the effect of vermiculite addition on composting food wastes from
      Korean households, food wastes were composted in three small bins to which
      different additives were added. The following three bins were employed: in Case
      I, only recycled compost was composted; in Case II, food wastes with recycled
      compost; and in Case III, food wastes with recycled compost and vermiculite. In
      the experiment performed for 30 days, it was confirmed that the supplementary
      addition of vermiculite to the composting mixture did not significantly improve
      the weight loss rate and the decomposition rate of food wastes. Due to dilution
      through the use of inorganic vermiculite, the vermiculite addition reduced the
      organic matter concentration of the composting mixtures. Vermiculite addition did
      not raise the pH value. Weight losses of roughly 70% were observed based on
      calculating moisture loss as well as dry food waste loss and not considering
      additives, while dry food waste loss was 29.4% and 35.8% with and without the
      addition of vermiculite, respectively. For these experiments, the major portion
      of the weight loss was the loss of water. The results indicate a need to
      differentiate between weight loss percentages and decomposition percentages, and
      a need to indicate if either of these percentages includes or excludes the mass
      of additives.

PMID- 15567664
TI  - A systems analysis tool for construction and demolition wastes management.
AB  - Managing construction and demolition (C&D) wastes has challenged many
      municipalities with diminishing waste disposal capacity. Facing such challenges,
      the Massachusetts Department of Environmental Protection proposed a policy
      restricting the landfill disposal of certain C&D waste materials, if unprocessed.
      This research is to study the potential economic impact of such restriction on
      construction contractors and C&D waste processors. A spreadsheet-based systems
      analysis model has been developed to assist the cost-benefit evaluation for
      various C&D waste management scenarios. The model, developed based on the mass
      balance principle, is designed to track a C&D waste stream through the various
      stages of a waste management system, i.e. generation, source separation,
      processing, recycling, and final disposal. This model, by incorporating the
      material flow data with the cost/revenue data associated with each management
      activity, can then provide an economic analysis for a proposed C&D waste
      management scenario. A case study illustrating the application of this model for
      Massachusetts is also presented.

PMID- 15567665
TI  - Re-cycling of sugar-ash: a raw feed material for rotary kilns.
AB  - Large amounts of sugar-ash, a material rich in calcium carbonate, are produced as
      a by-product in the Greek Sugar Industry. This work explores the possibility of
      re-cycling sugar-ash for use in the lime industry. A representative sample of
      sugar-ash from the Plati Imathias sugar plant was studied by PXRD, TG/DTG,
      calcination experiments at temperatures between 650 and 1150 degrees C and
      experiments to determine the quality of the quicklime produced at temperatures
      between 850 and 1150 degrees C following methods described in ASTM C110 standard.
      The sugar-ash was found to consist of 90 wt% calcium rich minerals (calcite and
      monohydrocalcite) and 10 wt% amorphous material. Traces of quartz were also
      detected. The quicklime of highest quality was produced at 950 degrees C. It is
      concluded that this "useless" material (sugar-ash) can be re-cycled for use in
      rotary kilns in the lime industry at calcination temperatures up to 950-1000
      degrees C.

PMID- 15567666
TI  - Material flow analysis of RDF-production processes.
AB  - The authors evaluate the possibilities of modifying the chemical characteristics
      of refuse-derived fuels (RDF) that are processed from residual household waste by
      mechanical operations to achieve and assure quality targets for relevant chemical
      concentrations, especially for heavy metals and chlorine. Quality assurance in
      the production of RDF demands that, together with an enrichment of the calorific
      value, highly toxic waste components are selectively separated and concentrated
      in a small stream to produce high yields of a relatively low polluted fuel. Based
      on the method of material flow analysis, a process evaluation is developed that
      considers the aspect of minimizing hazardous chemicals along with classical
      process data such as yield and product quality. Data on specific concentration of
      hazardous chemicals in waste components and their distribution in residual
      household waste as well as the results from large-scale test runs using different
      separation techniques demonstrate that mechanical operations alone are
      insufficient for separating hazardous chemicals. In the test runs, chemical
      compounds such as chlorine, cadmium and lead were often concentrated in the
      product. Even using optimized techniques, the ability to reduce hazards in the
      product is limited due to the distribution of the element concentration in the
      various components of the waste stream.

PMID- 15567667
TI  - Rehabilitation of El Yahoudia dumping site, Tunisia.
AB  - As in all developing countries, cities in Tunisia face serious problems of
      environmental pollution caused mainly by the inadequate and inefficient final
      disposal of their generated solid wastes. The Tunisian government launched a
      development program including the construction of landfills in the main cities
      and the closure of the contaminated sites issued from solid wastes landrising
      practice. The project of the Henchir El Yahoudia landfill restoration is the
      first experience in this programme. It has been suggested to convert the site to
      a green park and to implement an ornamental plant nursery. The whole surface of
      the landfill is approximately 100 ha from which 30 ha have been already
      transformed to an urban recreational area and the remaining 70 ha have to be
      characterized for the project extension. A field investigation by boring was
      conducted in order to define the geological and the hydrogeological conditions,
      the vertical and horizontal wastes layer extension, content and degree of
      decomposition and the composition and quantities of leachate and landfill gas.
      Representative samples of waste, soil, groundwater and leachate were collected
      for laboratory analyses. Several of these borings were converted to piezometers
      to define the flow regime in the site. The results showed that the biogas (CH4,
      H2S, and CO2), leachate and waste, distribution in the site is mainly affected by
      the temporal variation of the site operating method. The underlying fissured clay
      layer facilitated leachate infiltration into the groundwater where high BOD, COD
      and nitrogen concentrations were registered.

PMID- 15567668
TI  - Variation in deformation properties of processed MSWI bottom ash: results from
      triaxial tests.
AB  - This study is part of a larger study of the mechanical properties of processed
      municipal solid waste incinerator bottom ash. The aim was to investigate the
      variation in deformation properties of the ash for future use in unbound road
      layers. The effect of the material variation was analysed in particular.
      Specimens of bottom ash from four different incinerator plants and four sampling
      periods over a period of one year were tested by means of cyclic load triaxial
      tests. The results showed that there were variations in the deformation
      properties of the materials. Although there were significant differences between
      incinerator plants, the seasonal fluctuations were not significant. The
      differences were mainly due to the organic matter content. For the cyclic stress
      levels used, the resilient modulus ranged between 60 and 140 MPa, which is
      comparable to that of sand, but the plastic/permanent deformation was lower than
      for sand. It was also shown that the organic content has a limiting effect on the
      resilient modulus. For the material studied, the resilient modulus increased by
      50% when the content of organic matter was halved.

PMID- 15567669
TI  - Characteristics of bricks made from waste steel slag.
AB  - The characteristics of bricks made from steel slag were investigated in this
      research. Slag addition was shown to reduce the required firing temperature. When
      the firing temperature was greater than 1050 degrees C and the slag addition less
      than 10%, the bricks met ROC national standard CNS 3319 third-class brick for
      builders. The percentage of slag increased as the quartz and kaolin decreased in
      the sintered samples while the magnesium aluminum silicate and calcium silicate
      increased. There were no new crystal phases observed in these samples.

PMID- 15567670
TI  - Environmental management of construction and demolition waste in Kuwait.
AB  - There is an increasing pressure on the construction industry to reduce costs and
      improve the quality of our environment. The fact is that both of these goals can
      be achieved at the same time. Although construction and demolition (C&D)
      constitutes a major source of waste in terms of volume and weight, its management
      and recycling efforts have not yet seen the light in Kuwait. This study focuses
      on recycling efforts leading to the minimization of the total C&D waste that is
      currently landfilled in Kuwait. This paper presents the current status of C&D
      waste disposal system in Kuwait and identifies the potential problems to the
      environment, people and economy. Then, it investigates alternative solutions to
      manage and control this major type of waste in an economically efficient and
      environmentally safe manner. Next, the paper describes the feasibility of
      establishing a C&D waste recycling facility in Kuwait. It concludes by
      highlighting the major benefits and bottleneck problems with such a recycling
      facility.

PMID- 15567671
TI  - A review of environmental and economic regulations for promoting industrial waste
      recycling in Taiwan.
AB  - The objective of this paper is to present a compilation of recent Taiwan
      government laws/regulations to promote industrial waste recycling. The
      description is thus centered on legislation/regulations concerning general
      industrial wastes recycling in the policies of environmental protection, economic
      incentives and engineering technologies (3E) that have become effective since
      2001. The regulatory system, including Waste Disposal Act, Resource
      Recycling/Reuse Act, Environmental Basis Law, and Statute for Upgrading
      Industries, not only gives financial incentives, but also provides technical
      assistance and information transfer on promoting industrial waste recycling. In
      order to further utilize the recyclable resources and upgrade the environmental
      technology, Taiwan's Environmental Protection Administration (EPA), in
      cooperation with the Ministry of Economic Affairs (MOEA), has jointly ventured
      some promotion programs, which highlight an Industrial Waste Exchange Information
      Center and Environmental Technology Park Development Program, also described in
      the paper.

PMID- 15567672
TI  - Service improvement: tell us your story.

PMID- 15567673
TI  - Bowel management in the intensive care unit.
AB  - The area of bowel care in the intensive care unit (ICU) is often overlooked in
      the holistic care of the critically ill individual. With the primary concern of
      optimising patients to preserve life the problem of bowel care has been given
      less priority. The guidelines included within this service improvement paper
      offer a simple approach to bowel care management with the use of an algorithm and
      visual display score to be used in conjunction with the algorithm. This was
      developed in the intensive care unit of the Royal Free Hospital, London and is
      presently in use.

PMID- 15567674
TI  - A review of the nursing care of enteral feeding tubes in critically ill adults:
      part I.
AB  - Enteral tubes are frequently used in critically ill patients for feeding and
      gastric decompression. Many of the nursing guidelines to facilitate the care of
      patients with enteral tubes have not been based on current research, but on
      ritual and opinion. Using a computerised literature search and an evidence-based
      classification system as described by the Joanna Briggs Institute for Evidence
      Based Nursing and Midwifery (JBI), a comprehensive review was undertaken of
      enteral tube management. Several nursing practices related to enteral tube
      management are described. Evidence to support alternate methods of tube placement
      assessment other than abdominal X-ray was inconclusive. Enteral feeding should
      continue if gastric residual volumes are not considered excessive, as feeding is
      often withheld unnecessarily. Frequency of checking gastric residual volumes is
      largely opinion based and varies considerably, but prokinetics that aid gastric
      emptying should be used if absorption of feeds is problematic. Other
      recommendations include continuous rather than intermittent feeding, semi
      recumbent positioning to reduce the risk of airway aspiration and diligent
      artificial airway cuff management. Contamination of feeds can be minimised by
      minimal, meticulous handling and the use of closed rather than open systems.
      Generally, there was little high quality evidence to support practice
      recommendations leaving significant scope for further research by nurses in the
      management of patients with enteral tubes.

PMID- 15567675
TI  - Opioid and benzodiazepine withdrawal symptoms in paediatric intensive care
      patients.
AB  - The purposes of this prospective repeated measures study were to: (a) describe
      the occurrence of withdrawal symptoms with the use of a standardised protocol to
      slowly taper opioids and benzodiazepines; and (b) to test the predictive validity
      of an opioid and benzodiazepine withdrawal assessment scoring tool in critically
      ill infants and young children after prolonged opioid and benzodiazepine therapy.
      Fifteen children (6 weeks-28 months of age) with complex congenital heart disease
      and/or respiratory failure who received opioids and benzodiazepines for 4 days or
      greater were evaluated for withdrawal symptoms using a standardized assessment
      tool. Thirteen children showed moderate to severe withdrawal symptoms a median 3
      days after commencement of tapering. Symptom intensity was not related to prior
      opioid or benzodiazepine exposure, extracorporeal membrane oxygenation (ECMO)
      therapy or length of tapering. Children who received fentanyl in addition to
      morphine more often exhibited signs of withdrawal. This study demonstrated that
      significant withdrawal symptoms occur in critically ill children even with the
      use of a standardised assessment tool and tapering management protocol. The
      predictive validity and utility of the Opioid and Benzodiazepine Withdrawal Score
      (OBWS) was adequate for clinical use, but areas for further improvement of the
      tool were identified. Problems with the clinical withdrawal prevention and
      management guidelines were also identified. More research is needed to establish
      the optimal methods for prevention and management of iatrogenic opioid and
      benzodiazepine withdrawal in paediatric critical care.

PMID- 15567676
TI  - Omissions and errors during oxygen therapy of hospitalized patients in a large
      city of Greece.
AB  - Omissions and errors are commonly found concerning hospital oxygen use and the
      use of nebulizers. The aim of the study was to record oxygen use in seven
      hospitals located in a large district city of Greece. Another aim was to record
      the use of nebulizers in the same hospitals. We included 105 head nurses (HNs)
      working in seven hospitals of a large city district of Greece. Data were
      collected after interviewing each HN using a questionnaire and completing an
      anonymous data form. Data are expressed as percentages and analyzed using the chi
      square test. We found that 41% of HN believed O(2) is a gas that improves
      patient's dyspnea. The majority of the nurses (88.6%) stated that there was no
      protocol for O(2) therapy in the departments in which they worked. We found that
      O(2) therapy was commonly started, modified, discontinued by nurses in the
      absence of a medical order. Oxygen therapy was commonly not guided by arterial
      blood gas (ABG) analysis. We also found that there are no guidelines to prevent
      O(2) therapy interruption during intra-hospital transportation, and that few
      measures were taken to prevent O(2) explosion. In 95.2% of the departments the
      nebulizers were filled with tap water and were not changed on a daily basis
      (81.2%). Our results indicate that educational programmes, nursing protocols and
      guidelines are becoming mandatory in our country in order to ensure the proper
      use of O(2) therapy and nebulizers.

PMID- 15567677
TI  - Methods to prevent ventilator-associated lung injury: a summary.
AB  - Mechanical ventilation can cause ventilator-associated lung injury (VALI). This
      may manifest itself in various forms such as pneumothorax or, at the most extreme
      level, multi-system organ failure. The exact mechanisms by which the injury
      occurs are not known but appear to involve the conversion of mechanical
      stimulation of alveolar membranes into intracellular signalling, with subsequent
      upregulation of inflammatory mediators that produce the damage. This has been
      termed biotrauma. Furthermore, disruption of alveolar-capillary membranes may
      allow the release of these mediators into the systemic circulation that underpins
      the systemic inflammatory response syndrome. Various protective ventilatory
      strategies may be employed in order to reduce the lung damage and shall be
      discussed in this paper.

PMID- 15567678
TI  - Examining discharge outcomes and health status of critically ill patients: some
      practical considerations.
AB  - This prospective observational study examined the outcomes of 200 consecutive
      admissions to an adult tertiary level Intensive Care Unit (ICU). Eligible and
      consenting participants were also involved in a sub-study that examined health
      status at four measurement points from pre-illness to 6 months post-discharge. Of
      the 189 individual patients admitted, 23% died in ICU and 57% were discharged
      home. The health status sub-study enrolled 34 participants (39% of eligible
      patients) who were representative of the ICU population for demographic and
      clinical variables. Surviving participants returned to a similar, though not
      identical state of health at 6 months post-discharge, when compared to their pre
      ICU health-state using the 15D and SF-36 instruments. Health status at ICU
      discharge was significantly impaired when compared to other measurement points,
      particularly for mobility, breathing, eating, usual activities and vitality. A
      number of methodological challenges were evident, particularly for the health
      status sub-study, including prospective subject recruitment and retention, losses
      to follow-up and instrument responsiveness. Despite the limitations noted, the
      study provided useful findings and recommendations for the continued development
      of methods to examine the health status of critically ill patients.

PMID- 15567679
TI  - [Surveillance of maternal mortality in France: why and how?].

PMID- 15567680
TI  - [Embolization of uterine arteries for uterine fibroids: state-of-the-art].
AB  - Embolization of uterine arteries for fibroids is a modern minimally invasive
      method for treatment of uterine fibroids. Results from published data show a
      substantial short-term uterine reduction, an improvement in menorrhagias, and a
      reduction in fibroid related pain. Hospital stay and recovery are shortened
      compared with hysterectomy. One randomised comparative trial EAU vs hysterectomy
      has showed a reduction in hospital stay length and in the rate of major
      complications, but an increased rate of minor complications. Pregnancies and
      uneventful deliveries have been reported after uterine arteries embolization.
      Rare but severe complications have been described. Embolization of uterine
      arteries can be considered as a safe alternative to hysterectomy or myomectomy in
      selected cases. It cannot be a routine method for treating fibroids with women of
      childbearing age.

PMID- 15567681
TI  - [Effect of laparoscopic trocar model on the quality of the movement: experimental
      study of friction].
AB  - OBJECTIVE: To keep the pneumoperitoneum and the tightness of the abdominal and
      pelvic cavity during a laparoscopy, the sheaths of trocar are provided with a
      device (valvule, membranes etc.) inducing a friction during the handling of the
      instrument. The objective of this article is to analyse friction from different
      types of trocar's port. MATERIALS AND METHODS: We present here the experimental
      results obtained during a testing bench of three different trocar sheaths. The
      mechanism of tightness of the first trocar sheath is made of a fine membrane
      associated to a valve, of a thick membrane for the second trocar sheath, whereas
      the third trocar sheath is made of two membranes, a fine and a thick, associated
      to a valve. After reporting the experimental device and the analytic model
      adopted to describe the relationship between the measured physical parameters, we
      lay out our results. The identification of parameters of this model makes it
      possible to objectively compare the three trocars. RESULTS: Our results revealed
      that, under experimental conditions, the amplitude of friction was significantly
      lower with trocar's port provided with a valve and a fine membrane than with both
      other ports (fivefold weaker). DISCUSSION AND CONCLUSION: We evoke the importance
      of the possible disruption brought by these frictions while referring these
      values to those of other measurements concerning interactions between instrument
      and organs. These different behaviours of the material could have some
      consequences in choosing the tools for the performance of precise gestures.

PMID- 15567682
TI  - [Obstetrical prognosis improvement in patients exposed in utero to
      diethylstilbestrol with specific care management].
AB  - OBJECTIVE: To define the interest of a specific care management of pregnancies in
      patients exposed in utero to diethylstilbestrol, with the intention of reducing
      the number of spontaneous miscarriage and prematurity. PATIENTS AND METHODS: One
      hundred and three pregnancies in 49 patients exposed in utero to
      diethylstilbestrol were followed during a 4-year study, while establishing a
      specific care management of pregnancies in those women. RESULTS: Spontaneous
      miscarriage rate was 18.5%, among which 16.5% before 15 weeks of pregnancy and 2%
      after 15 weeks of pregnancy. Premature birth rate was 41.9%, among which 10.8% of
      great premature birth (before 32 weeks of pregnancy), 13.5% of moderate premature
      birth (between 32 and 36 weeks of pregnancy), and 17.6% of minor prematurity
      (after 36 weeks of pregnancy). The patients' average delivery term was 36 +/-3.6
      weeks. DISCUSSION AND CONCLUSION: As compared with the literature data, our
      miscarriage and prematurity rates are found to be lower. Our specific care
      management seems thus to be effective.

PMID- 15567683
TI  - [Endorectal sonography in gynecology: usefulness and diagnostic accuracy].
AB  - OBJECTIVE: The aim of this study was to assess feasibility and diagnostic
      accuracy of endorectal sonography (ERS) in comparison with transabdominal
      sonography (TAS) in women with a contraindication to endovaginal sonography
      (EVS). PATIENTS AND METHODS: ERS was proposed to 32 patients in the immediate
      continuation of TAS. It was performed either with a specific probe or with a
      vaginal probe. The protocol included a complete evaluation of pelvic structures
      observed with both sonographic techniques. RESULTS: After counselling and assent,
      29 of the 32 patients (90%) accepted ERS. The examination was regarded as
      complete in 28 cases. ERS confirmed the absence of pelvic anomaly in the 12 cases
      of normal TAS. ERS modified diagnosis in 5 of the 8 cases of anechoic ovarian
      cysts seen in TAS. In 4 cases, PCOs not seen in TAS were identified. Two
      partially sub-mucous myomas not recognized by TAS were diagnosed by ERS.
      Sensibility, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of TAS and ERS were 38,4 and 87,5%, 41,6 and 100%, 50 and 100%, 40
      and 85,7% respectively. DISCUSSION AND CONCLUSION: These findings suggest ERS is
      an effective diagnostic tool in pelvic exploration when EVS cannot be performed.
      It should be widely proposed after information and assent.

PMID- 15567684
TI  - [The use of clomiphene citrate in ambulatory medicine practice in the Midi
      Pyrenees area: compliance to national guidelines applicable to infertility
      diagnosis and to prescription and monitoring rules applicable to clomiphene
      citrate treatments].
AB  - OBJECTIVE: Evaluate the compliance to the national guidelines from ANDEM (1996)
      and AFSSAPS (2003) concerning the diagnosis of infertility, the prescription of
      clomiphene and the monitoring of these treatments. PATIENTS AND METHODS:
      Retrospective study of female patients from 16 to 50 y.o. having benefited from
      reimbursement of clomiphene citrate treatment between 1st April 2002 and 30th
      June 2002. After random sampling stratified on age, data on diagnosis procedures
      and treatments were extracted from the Social Security reimbursement database.
      These data were validated and completed by patients' interviews. RESULTS: A total
      of 283 women were included. 30% were subject to the basic hormonal tests (FSH,
      LH, estradiol). The proportion of patients explored by hysterosalpingogram, post
      coital test and echography were respectively 50%, 35% and 68%. A semen analysis
      was found in 60% of the partners. The complete set of recommended tests before
      start of treatment was realised in 1.5% of women. In 7% of cases, women were
      treated without prior exploration. The proportion of tests performed was
      comparable below and above the age of 35. 77% of treatments were initiated after
      at least one year of waiting for a spontaneous conception. 69% of women were
      monitored during treatment by other methods than clinical follow-up. CONCLUSION:
      Prescription of clomifene citrate is too frequently realised without compliance
      to guidelines applicable to infertility investigations and therefore without
      persuasive diagnosis. These practices can lead to loss of childbearing
      opportunities and complications.

PMID- 15567685
TI  - [medullar adhesive arachnoiditis: a late complication after obstetrical epidural
      analgesia].
AB  - A 30-year-old woman, G3P3, was progressively affected by spastic paraparesis with
      loss of sensitivity and urinary incontinence due to medullar adhesive
      arachnoiditis occurring five months after an epidural analgesia for repeat
      cesarean section. Magnetic resonance imaging showed a voluminous subarachnoid
      cyst and a septated syringomyelic cavitation attributed to metabisulfite, the
      preservative of epinephrine and to multiple lidocaine injections through the
      catheter in the postoperative period. Despite two decompressive neurosurgical
      operations, the neurological state of the patient continues to worsen.

PMID- 15567686
TI  - [Ultrasonographic view and women's behaviour before first-trimester induced
      abortion].
AB  - Women's behaviour before induced abortion during an ultrasonographic exam was
      described. A psychosomatic analysis was carried out in the discussion to try to
      explain the different women's attitudes. Most women do not want to see
      ultrasonographic scan or keep photographs. One must of course respect women's
      choices as to their desire to see or not the ultrasound image of their foetus
      when pre-induced abortion ultrasound examination is performed. One should
      nonetheless be able to listen to their request, be it implicit.

PMID- 15567687
TI  - [Fetal and umbilical blood cord stem cells: a room for the obstetrician and
      gynaecologist. Part two].
AB  - Stem cells are undifferentiated cells, with the ability to self renew and to
      differentiate into specialised cells. Besides embryonic stem cells, adult, fetal
      and umbilical cord blood (UB) stem cells are to be distinguished. These cells are
      multipotent. Embryonic germ cells (EG) that also are fetal stem cells have proven
      to be truly pluripotent, since they are able to give derivatives of the three
      primitive embryonic layers. EG cells have a normal karyotype, and exhibit
      remarkable long-term proliferative potential. Fetal stem cells and UB cells have
      already been used in cell therapy trials (e.g., Parkinson's disease, congenital
      immunodeficiencies and hemopathies). The applications in the field of
      reproductive biology will lead to a better understanding of genomic imprinting
      with EG cells. The obstetrician and gynaecologist could act a central part in the
      production and study of fetal stem cells, using tissues from aborted fetuses or
      collecting cord blood stem cells.

PMID- 15567688
TI  - [Adenomyosis: what imaging modality in the diagnosis and staging?].
AB  - Adenomyosis constitutes the most frequent myometrial disorder with leiomyoma. Its
      clinical diagnosis is often difficult. After giving a histopathologic definition,
      the semiology, the limits, and the diagnostic role of hysterography,
      transabdominal and endovaginal sonography and MRI will be discussed.

PMID- 15567689
TI  - [How to avoid the uncertainties of intraoperative examination of the sentinel
      lymph node in breast cancer?].
AB  - The sentinel lymph node procedure is now admitted by many teams for axillary
      evaluation in the early stage of breast cancer. The classical technique consists
      in an intraoperative examination of the sentinel lymph node under general
      anaesthesia during tumorectomy, deciding whether or not complete axillary
      lymphadenectomy must be done. Intraoperative examination seems to us to have a
      poor predictive value. In the case of a false positive, the surgeon would perform
      lymphadenectomy unnecessarily, while a false negative would mean that the patient
      would have to be re-operated for lymphadenectomy once the definitive results have
      become available. For all these reasons, we propose the detection of the sentinel
      lymph node under local anaesthesia and to await its definitive analysis before
      carrying out tumorectomy on the patient and axillary lymphadenectomy if necessary
      under general anesthesia. Hence, we consider that the best way to avoid the
      uncertainties of an intraoperative examination of the sentinel lymph node is not
      to carry out intraoperative examinations.

PMID- 15567690
TI  - [Woman voluntary sterilization: law and freedom, rights and duties].

PMID- 15567691
TI  - [Woman voluntary sterilization: law and freedom, rights and duties. Should one
      consider tying of the Fallopian tubes for contraception as a "right"?].

PMID- 15567692
TI  - [Woman voluntary sterilization: law and freedom, rights and duties. To legalize
      does not mean to impose].

PMID- 15567693
TI  - [Recommendations for clinical practice: 2003 standards, options and
      recommendations for the medical front-line treatment of patients with malignant
      epithelial ovarian tumors. Update (summary version)].

PMID- 15567697
TI  - [Previous cesarean section is an operative risk factor in vaginal hysterectomy.
      Gynecol Obstet Fertil 2004; 32: 391-395].

PMID- 15567698
TI  - Heterogeneous nanomechanical properties of superficial and zonal regions of
      articular cartilage of the rabbit proximal radius condyle by atomic force
      microscopy.
AB  - Articular chondrocytes have been thought to reside in a homogenous matrix. The
      physical characteristics of the intercellular matrix of articular cartilage are
      not well characterized, especially at a nanoscopic scale. The present work tested
      the hypothesis that the nanomechanical properties of the intercellular matrices
      of articular cartilage in both the articulating surface and various cellular
      zones are non-homogeneous. Nanoindentation by atomic force microscopy was applied
      to the geometric center of the medial, lateral and groove regions of the
      superficial zone of the rabbit proximal radius cartilage, and then the
      intercellular matrices of chondrocytes from the superficial to calcifying zones
      in 40 microm increments. The elastic modulus of the articular surface of the
      medial condyle (1.46+/-0.11 MPa) was significantly higher than the lateral
      condyle (1.18+/-0.10 MPa), and the groove (0.96+/-0.07 MPa). There is a
      significant gradient increase in Young's moduli from the superficial zone (0.52+/
      0.05 MPa) to calcifying zone (1.69+/-0.12 MPa). Thus, the nanomechanical
      properties of the intercellular matrices of the articulating surface are region
      specific and likely related to articular function. Heterogeneous biophysical
      properties of intercellular matrices along the depth from the superficial to
      calcifying zones suggest that chondrocytes likely reside in a heterogeneous
      matrix.

PMID- 15567699
TI  - Ultrasound image-based computer model of a common carotid artery with a plaque.
AB  - Ultrasound scans were acquired from a common carotid artery in a patient with an
      early atherosclerotic plaque forming a mild asymmetrical stenosis. The 3D
      vascular geometry of the diseased arterial segment was reconstructed from a
      series of 2D cross-sectional images, and computational meshes for the flow and
      wall domains were developed. Numerical flow simulations incorporating coupled
      fluid-solid interaction were implemented using flow and pressure waveforms
      measured in vivo. The effects of wall distensibility were investigated by
      comparing the predictions obtained with different wall compliance, one with
      'natural' compliance and another with a stiffer wall. Limited flow separation was
      predicted in the post-stenotic zone. The non-uniform thickness of the diseased
      wall restricted the wall motion locally and re-distributed the stress, giving
      raised concentrations at the plaque shoulders.

PMID- 15567700
TI  - Non-invasive approach towards the in vivo estimation of 3D inter-vertebral
      movements: methods and preliminary results.
AB  - A kinematical model of the lower spine was designed and used to obtain a robust
      estimation of the vertebral rotations during torso movements from skin-surface
      markers recorded by video-cameras. Markers were placed in correspondence of the
      anatomical landmarks of the pelvic bone and vertebral spinous and transverse
      processes, and acquired during flexion, lateral bending and axial motions. In the
      model calibration stage, a motion-based approach was used to compute the rotation
      axes and centres of the functional segmental units. Markers were mirrored into
      virtual points located on the model surface, expressed in the local reference
      system of coordinates. The spine motion assessment was solved into the domain of
      extended Kalman filters: at each frame of the acquisition, the model pose was
      updated by minimizing the distances between the measured 2D marker projections on
      the cameras and the corresponding back-projections of virtual points located on
      the model surface. The novelty of the proposed technique rests on the fact that
      the varying location of the rotation centres of the functional segmental units
      can be tracked directly during motion computation. In addition, we show how the
      effects of skin artefacts on orientation data can be taken into account. As a
      result, the kinematical estimation of simulated motions shows that orientation
      artefacts were reduced by a factor of at least 50%. Preliminary experiments on
      real motion confirmed the reliability of the proposed method with results in
      agreement with classical studies in literature.

PMID- 15567701
TI  - Derivative weighted active insulin control modelling and clinical trials for ICU
      patients.
AB  - Close control of blood glucose levels significantly reduces vascular
      complications in Type 1 and Type 2 diabetic individuals. Heavy derivative
      controllers using the data density available from emerging biosensors are
      developed to provide tight, optimal control of elevated blood glucose levels,
      while robustly handling variation in patient response. A two-compartment glucose
      regulatory system model is developed for intravenous infusion from
      physiologically verified subcutaneous infusion models enabling a proof-of-concept
      clinical trial at the Christchurch Hospital Department of Intensive Care
      Medicine. This clinical trial is the first of its kind to test a high sample rate
      feedback control algorithm for tight glucose regulation. The clinical trial
      results show tight control with reductions of 79-89% in blood glucose excursions
      for an oral glucose tolerance test. Experimental performance is very similar to
      modelled behaviour. Results include a clear need for an additional accumulator
      dynamic for insulin behaviour in transport to the blood and strong correlation of
      10% or less between modelled insulin infused and the amounts used in clinical
      trials. Finally, the heavy derivative PD control approach is seen to be able to
      bring blood glucose levels below the (elevated) basal level, showing the
      potential for truly tight control.

PMID- 15567702
TI  - Basic behavior of the finite helical axis in a simple tooth movement simulation.
AB  - A finite helical axis (FHA) analysis can provide precise three-dimensional
      information on orthodontic tooth movement compared to an analysis based on a
      rectangular coordinate system. The FHA has already been applied in an analysis of
      orthodontic tooth movement. Interestingly, the position of the FHA changes
      dramatically in different stages of treatment; however, no previous report has
      provided detailed information of its basic behavior for clinicians. The purpose
      of this study was to clarify the basic behavior of the FHA in simple tooth
      movement, which could promote a better understanding of the 3-D orientation of
      and rotation about the FHA during tooth movement. Parameters of the FHA were
      calculated from a simulation of canine retraction. As the tipping angle of the
      canine was increased from 5 degrees to 30 degrees , the orientation vector of the
      FHA approached the most affected axis of rotation (on a rectangular coordinate
      system) in a non-linear manner. The angle of rotation about the FHA also
      increased in a non-linear manner. This non-linear problem was solved
      analytically. The basic behavior of the orientation vector of the FHA and the non
      linear characteristics of the FHA parameters clarified in this study should be
      important for the future analysis of actual tooth movement based on the FHA.
      However, we must be aware that the non-linearity of the FHA itself may affect the
      analysis of the mechanical properties of the periodontal tissue.

PMID- 15567703
TI  - An investigation of the effect of electrode size and electrode location on
      comfort during stimulation of the gastrocnemius muscle.
AB  - The use of surface neuromuscular electrical stimulation (SNMES) in medicine is
      well established. However, discomfort has been identified as limiting the use of
      SNMES in these applications. This pilot study investigated the influence of
      various electrode sizes and their positioning on perceived pain and discomfort
      during neuromuscular electrical stimulation (NMES) of the gastrocnemius muscle
      using surface electrodes. This study formed part of a research project to develop
      a therapeutic device for calf muscle blood flow assist applications. Twelve
      healthy subjects (n=12) participated in this pilot study. Each participant
      attended the trial centre for testing which consisted of SNMES to four different
      electrode stimulation sites using two electrode sizes (round with areas 19.63 and
      38.48 cm2). Comfort was assessed by asking the subjects to indicate the
      stimulation amplitude corresponding to the onset of discomfort (pain threshold)
      and the amplitude at which the discomfort became unbearable (pain tolerance). Of
      the four stimulation sites tested, two were deemed unsuccessful as it was very
      difficult to obtain a muscle contraction using these sites, while the remaining
      two sites elicited good muscle contraction. The most comfortable stimulation was
      achieved by placing the cathode electrode high on the calf, below the proximal
      end of the muscle heads and the anode electrode towards the end of the muscle
      belly and when the 19.63 cm2 electrodes were used at these sites (p=<0.001).

PMID- 15567704
TI  - A method for reduction of power line interference in the ECG.
AB  - A method for reduction of power line interference (PLI) in electrocardiograms
      with sampling rate integer multiple of the nominal power line frequency is
      developed and tested using simulated signals and records from the databases of
      the American Heart Association and the Massachusetts Institute of Technology. The
      method involves parabolic detrending of the ECG, estimation of the signal
      components with frequencies corresponding to PLI by discrete Fourier transform,
      and minimum-squared-error approximation of decimated series of averaged
      instantaneous values of PLI using appropriately defined weights. Tests of the
      proposed method with simulated data show that for signal-to-noise ratios SNR
      greater than 25 dB, the logarithmic relative error is below -32 dB and the error
      to-signal ratio is less than -24 dB. For lower SNR, the errors increased, and a
      noise attenuation of 0.6 dB is observed. The main advantage of the developed
      method in comparison with other simpler and faster approaches is the accurate
      interference reduction in cases when the power line frequency deviates from the
      nominal 50 or 60 Hz. Due to computational burden, the method is more suitable for
      off-line application, but real-time implementation, using modern processors, is
      also possible.

PMID- 15567705
TI  - Feature characterization in fMRI data: the Information Bottleneck approach.
AB  - Clustering is a well-known technique for the analysis of Functional Magnetic
      Resonance Imaging (fMRI) data, whose main advantage is certainly flexibility:
      given a metric on the dataset, it "summarizes" the main characteristics of the
      data. But intrinsic to this approach are also the problem of defining correctly
      the quantization accuracy, and the number of clusters necessary to describe the
      data. The Information Bottleneck (IB) approach to vector quantization, proposed
      by Bialek and Tishby, addresses these difficulties: (1) it deals with an explicit
      trade-off between quantization and data fidelity; (2) it does so during the
      clustering procedure and not post hoc; (3) it takes into account the full
      statistical distribution of the features within the feature space and not only
      their most likely value; last, it is principled through an information theoretic
      formulation, which is relevant in many situations. In this paper, we present how
      to benefit from this method to analyze fMRI data. Our application is the
      clustering of voxels according to the magnitude of their responses to several
      experimental conditions. The IB quantization provides a consistent representation
      of the data, allowing for an easy interpretation and comparison of datasets.

PMID- 15567706
TI  - Registration of medical images using an interpolated closest point transform:
      method and validation.
AB  - Image registration is an important procedure for medical diagnosis. Since the
      large inter-site retrospective validation study led by Fitzpatrick at Vanderbilt
      University, voxel-based methods and more specifically mutual information-based
      registration methods (see for instance [IEEE Trans. Med. Imag. 22 (8) (2003) 986]
      for a review on these methods) have been regarded as the method of choice for
      rigid-body intra-subject registration problems. In this study we propose a method
      that is based on the Iterative Closest Point algorithm and a pre-computed closest
      point map obtained with a slight modification of the fast marching method
      proposed by Sethian. Pre-computing the closest point map speeds up the process
      because at each iteration point correspondence can be established by table
      lookup. We also show that because the closest point map is defined on a regular
      grid it introduces a registration error and we propose an interpolation scheme
      that addresses this issue. The method has been tested both on synthetic and real
      images, and registration results have been assessed quantitatively using the data
      set provided by the Retrospective Registration Evaluation Project. For these
      volumes, MR and CT head surfaces were extracted automatically using a level-set
      technique. Results show that on these data sets this registration method leads to
      accuracy numbers that are comparable to those obtained with voxel-based methods.

PMID- 15567707
TI  - Mutual information in coupled multi-shape model for medical image segmentation.
AB  - This paper presents extensions which improve the performance of the shape-based
      deformable active contour model presented earlier in [IEEE Conf. Comput. Vision
      Pattern Recog. 1 (2001) 463] for medical image segmentation. In contrast to that
      previous work, the segmentation framework that we present in this paper allows
      multiple shapes to be segmented simultaneously in a seamless fashion. To achieve
      this, multiple signed distance functions are employed as the implicit
      representations of the multiple shape classes within the image. A parametric
      model for this new representation is derived by applying principal component
      analysis to the collection of these multiple signed distance functions. By
      deriving a parametric model in this manner, we obtain a coupling between the
      multiple shapes within the image and hence effectively capture the co-variations
      among the different shapes. The parameters of the multi-shape model are then
      calculated to minimize a single mutual information-based cost criterion for image
      segmentation. The use of a single cost criterion further enhances the coupling
      between the multiple shapes as the deformation of any given shape depends, at all
      times, upon every other shape, regardless of their proximity. We found that this
      resulting algorithm is able to effectively utilize the co-dependencies among the
      different shapes to aid in the segmentation process. It is able to capture a wide
      range of shape variability despite being a parametric shape-model. And finally,
      the algorithm is robust to large amounts of additive noise. We demonstrate the
      utility of this segmentation framework by applying it to a medical application:
      the segmentation of the prostate gland, the rectum, and the internal obturator
      muscles for MR-guided prostate brachytherapy.

PMID- 15567708
TI  - Strategies for brain shift evaluation.
AB  - For the analysis of the brain shift phenomenon different strategies were applied.
      In 32 glioma cases pre- and intraoperative MR datasets were acquired in order to
      evaluate the maximum displacement of the brain surface and the deep tumor margin.
      After rigid registration using the software of the neuronavigation system, a
      direct comparison was made with 2D- and 3D visualizations. As a result, a great
      variability of the brain shift was observed ranging up to 24 mm for cortical
      displacement and exceeding 3 mm for the deep tumor margin in 66% of all cases.
      Following intraoperative imaging the neuronavigation system was updated in eight
      cases providing reliable guidance. For a more comprehensive analysis a voxel
      based nonlinear registration was applied. Aiming at improved speed of alignment
      we performed all interpolation operations with 3D texture mapping based on OpenGL
      functions supported in graphics hardware. Further acceleration was achieved with
      an adaptive refinement of the underlying control point grid focusing on the main
      deformation areas. For a quick overview the registered datasets were evaluated
      with different 3D visualization approaches. Finally, the results were compared to
      the initial measurements contributing to a better understanding of the brain
      shift phenomenon. Overall, the experiments clearly demonstrate that deformations
      of the brain surface and deeper brain structures are uncorrelated.

PMID- 15567709
TI  - Adaptive registration using local information measures.
AB  - Rapidly advancing registration methods increasingly employ warping transforms.
      High degrees of freedom (DOF) warpings can be specified by manually placing
      control points or instantiating a regular, dense grid of control points
      everywhere. The former approach is laborious and prone to operator bias, whereas
      the latter is computationally expensive. We propose to improve upon the latter
      approach by adaptively placing control points where they are needed. Local
      estimates of mutual information (MI) and entropy are used to identify local
      regions requiring additional DOF.

PMID- 15567710
TI  - Expression of Spgatae, the Strongylocentrotus purpuratus ortholog of vertebrate
      GATA4/5/6 factors.
AB  - Spgatae is the sea urchin ortholog of the vertebrate gata4/5/6 genes, as
      confirmed by phylogenetic analysis. The accumulation of Spgatae transcripts
      during embryonic development and the spatial pattern of expression are reported
      here. Expression was first detected in the 15 h blastula. The number of Spgatae
      RNA molecules increases steadily during blastula stages, with expression peaking
      during gastrulation. After gastrulation is complete, the level of expression
      decreases until the end of embryogenesis. Whole mount in situ hybridization
      showed that Spgatae transcripts were first detected in a ring of prospective
      mesoderm cells in the vegetal plate. Spgatae expression then expands to include
      the entire vegetal plate at the mesenchyme blastula stage. During gastrulation
      Spgatae is expressed at the blastopore, and at prism stage strongly in the
      hindgut and midgut but not foregut, and also in mesoderm cells at the tip of the
      archenteron. Towards the end of embryogenesis, expression in the hindgut
      decreases. The terminal pattern of expression is in midgut plus coelomic pouches.

PMID- 15567711
TI  - Wolbachia bacteria, the cause for false vesicular staining pattern in Drosophila
      melanogaster.
AB  - Majority of fly laboratory strains is infected with Wolbachia, intracellular
      rickettsial-type symbiotic bacteria widespread in various organisms including
      insects and nematodes. To make the matter worse, I found that certain antisera
      used for fly immunocytochemistry can recognize Wolbachia bacteria in addition to
      their own antigens, due to impurity in the antisera generated against the
      recombinant fusion proteins frequently used as antigens. Thus, combinatorial use
      of contaminated antisera and Wolbachia-infected flies can result in serious
      misinterpretations, which can be avoided by curing laboratory strains of
      Wolbachia.

PMID- 15567712
TI  - ang is a novel gene expressed in early neuroectoderm, but its null mutant
      exhibits no obvious phenotype.
AB  - To find genes that play roles in initial regionalization of anterior
      neuroectoderm, 15 novel genes were isolated that are expressed in anterior
      neuroectoderm at E8.0-E8.5. Moreover, to assess their functions by generation of
      mutant mice a conventional targeting strategy was designed, exploiting the
      availability of accurate long amplification PCR and BAC library that is coupled
      with genome information, in C57BL/6 strain. The ang is one of such genes; it has
      no known functional domains or no cognates, but is conserved not only in
      vertebrates, but also in Drosophila. Its expression was initially found
      throughout neuroectoderm at E7.5; subsequently the expression became high in
      rostral brain and caudal neuropore regions and low in hindbrain and spinal cord
      regions. At E12.5 the expression was found in undifferentiated neuroepithelium in
      ventricular zone, dorsal root ganglia and several non-neural tissues. However,
      ang null mutant was live-born without any apparent defects.

PMID- 15567713
TI  - Expression of retinoic acid-synthesizing and -metabolizing enzymes during
      nephrogenesis in the rat.
AB  - Vitamin A signaling through its active form retinoic acid (RA) plays a critical
      role during kidney development and vitamin A deficiency in the rat induces renal
      hypoplasia. Here, we describe the distribution of four enzymes of the RA
      synthetic pathway (aldehyde dehydrogenases ALDH1A1-3 and ALDH8A1) and two enzymes
      of the degradative pathway (CYP26A1 and CYP26B1) in the developing rat
      metanephros. We provide evidence that each enzyme displays a cell-type specific
      expression pattern that changes considerably in the course of renal organogenesis
      and nephron differentiation. ALDH1A2 expression was restricted to the cortical
      stroma cell population, whereas ALDH8A1 transcripts were present in emerging
      renal vesicles. CYP26A1 and CYP26B1 mRNAs were absent during this time. Following
      nephron induction, ALDH1A1 remained weakly expressed in the UB ends, but was
      highly expressed in the UB-connected tubule and in all differentiating tubular
      segments of the developing nephron. ALDH1A2 was strongly expressed in the
      visceral layer of the developing glomeruli, as well as in cortical collecting
      tubules. ALDH1A3 mRNAs were found in the developing papilla and ureter. During
      postnatal nephrogenesis, ALDH1A3 and ALDH8A1 were co-expressed in the ureteric
      bud ends. CYP26A1 and CYP26B1 were both expressed from E18.5 onwards in S-shaped
      bodies, in tubular and glomerular anlagen, respectively. On the last day of
      nephrogenesis in the rat, CYP26B1 expression extended to UB ends. Our results
      indicate that tubular and glomerular differentiation of the nephron relies upon
      precise control of the RA metabolic pathway.

PMID- 15567714
TI  - The FoxO-subclass in Xenopus laevis development.
AB  - Transcription factors of the Fox (fork head box) family are involved in cellular
      specification and determination processes. Here, we report on the isolation and
      first characterisation of two members of the FoxO subclass in Xenopus laevis,
      xFoxO1 and xFoxO3. These sequences exhibit 68% (67%) and 69% (70%) identity to
      their mouse (human) orthologues, respectively. Serine and threonine residues,
      which are phosphorylated upon insulin signalling, are evolutionarily conserved
      from frogs to mammals. xFoxO1 and xFoxO3 genes are maternally transcribed, but
      transcripts disappear during early cleavage stages. Zygotic transcription of both
      genes starts at the late neurula stages and transcripts accumulate at the end of
      organogenesis. While maternal transcripts of both genes are found within the
      animal half of the early embryo, zygotic transcripts show distinct patterns.
      xFoxO1 expression is observed in the pronephros, within head mesenchyme in front
      of the eye, within the branchial arches and in the liver primordium. At the late
      neurula, xFoxO3 is found to be specifically expressed in the anterior neural
      plate and in neural crest cells. Later, expression of xFoxO3 is observed in a
      variety of organs and tissues, like the head, the branchial arches and the
      somites.

PMID- 15567715
TI  - Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult
      tissues.
AB  - Members of the Forkhead box (Fox) transcription factors family Foxa1 (Hnf-3
      alpha), Foxa2 (Hnf-3 beta) are known to influence gene expression in endodermally
      derived tissues including lung, liver, pancreas, stomach, and intestine. In the
      present study, we have generated highly specific antibodies for Foxa1 and Foxa2
      and determined their expression patterns in the developing and adult mouse. Foxa1
      and Foxa2 were detected in the nuclei of tissues derived from both foregut and
      hindgut endoderm (liver, lung, pancreas, stomach, intestine, prostate and
      bladder). Foxa2 and Foxa1 were also detected in organs deriving from ectodermal
      (several brain structures and olfactory epithelium) and mesodermal origins
      (kidney, vagina and uterus, seminal and coagulating glands) during development.
      Colocalization and distinct sites of expression of Foxa1 and Foxa2 indicate
      unique as well as overlapping roles of Foxa1 or Foxa2 during morphogenesis and in
      the function of different adult organs.

PMID- 15567716
TI  - Expression of Dlk/Pref-1 defines a subpopulation in the oval cell compartment of
      rat liver.
AB  - We previously showed that Dlk, a transmembrane protein containing six epidermal
      growth factor like repeats in its extracellular domain, is strongly expressed in
      hepatoblasts in murine fetal liver. Here, we examined the expression of Dlk in
      oval cells, which are adult hepatic progenitors, in the rat 2
      acetylaminofluorene/partial hepatectomy (2AAF/PH) model. Reverse transcription
      polymerase chain reaction analysis showed that Dlk expression was significantly
      induced in the regenerating liver at day 12 and 14 after PH, when many oval cells
      were present in periportal areas. Immunofluoresence staining analysis revealed
      that Dlk(+) cells expressed oval cell markers, cytokeratin 19 (CK19) and alpha
      fetoprotein, indicating that Dlk is expressed in oval cells. However, Dlk(+)
      cells accounted for only about 20% of total CK19(+) oval cells. Dlk(+) cells were
      localized more distantly from the portal vein than Dlk(-) cells, and were
      adjacent to mature hepatocytes, though Dlk(+) cells were surrounded by the basal
      membrane as other oval cells. Furthermore, at day 12 after PH, only 3% of Dlk(+)
      oval cells expressed Ki67, whereas about 13% of total oval cells expressed Ki67,
      indicating that Dlk(+) oval cells are less proliferative than Dlk(-) oval cells.
      Taken together, these results demonstrate that Dlk is expressed in a
      subpopulation of oval cells and that Dlk(+) cells represent intermediate cells
      between Dlk(-) oval cells and mature hepatocytes.

PMID- 15567717
TI  - Expression of the sodium-driven chloride bicarbonate exchanger NCBE during
      prenatal mouse development.
AB  - In the immature central nervous system (CNS) GABA-mediated excitation is thought
      to be an important developmental signal. It depends on a high intracellular
      chloride concentration ([Cl(-)](i)) of the particular neuron. [Cl(-)](i) is a
      consequence of chloride transport processes across the plasma membrane. The
      ongoing expression of the KCl-co-transporter KCC2 eventually lowers [Cl(-)](i) in
      most CNS neurons and thus renders GABA hyperpolarizing. As NCBE, a sodium
      dependent chloride-bicarbonate exchanger, also lowers [Cl(-)](i) and may thus
      modulate the GABA-response, we analyzed its expression during prenatal mouse
      development before establishment of the mature KCC2 expression. Indeed, NCBE is
      expressed very early in CNS neurons and precedes the expression of KCC2. Unlike
      KCC2, NCBE is expressed in the peripheral nervous system and in non-neuronal
      tissues as the choroid plexus, the dura, and some epithelia including the acid
      secreting epithelium of the stomach and the duodenal epithelium.

PMID- 15567718
TI  - Expression of Xenopus tropicalis noggin1 and noggin2 in early development: two
      noggin genes in a tetrapod.
AB  - We report the identification of two distinct noggin genes in the tetrapod Xenopus
      tropicalis. Noggin functions to antagonize BMP signaling in many developmental
      contexts, and much work has explored its role in early vertebrate development. We
      have identified two noggin genes in the tropical clawed frog, X. tropicalis, a
      diploid anuran which is being explored for its potential as a genetic model
      system for early vertebrate development. Here we report the cloning and
      characterization of the Xenopus tropicalis noggin1 and noggin2 genes, which have
      distinct expression domains in the early embryo with one overlapping domain in
      the anterior neural tissue. X. tropicalis noggin1 expression is very similar to
      that of noggin in Xenopus laevis, with expression beginning in the blastula
      organizer region and continuing through gastrulation and neurulation in the
      organizer and notochord. Later, it is also expressed in the anterior neural ridge
      and subsequent forebrain; noggin1 is also expressed in the pharyngeal arches
      after neural tube closure. At the tadpole stage expression is maintained in the
      dorsal neural tube and is present in the otic vesicle. However, the expression of
      noggin2 is much more similar to the expression of noggin2 in D. rerio with
      expression in the forebrain, hindbrain, and somites, but unlike D. rerio, X.
      tropicalis noggin2 is expressed in the heart by stage 28. This work presents the
      first example of a tetrapod with at least two noggin genes.

PMID- 15567719
TI  - Co-expression of de novo DNA methyltransferases Dnmt3a2 and Dnmt3L in gonocytes
      of mouse embryos.
AB  - In mouse male germ cells, global DNA methylation occurs in gonocytes at 16-18
      days postcoitum. In the present study, we examined which de novo-type DNA
      methyltransferase, Dnmt3a, Dnmt3a2 or Dnmt3b is expressed in gonocytes at these
      stages. Immuno-histochemical and Western blot analyses revealed that Dnmt3a2 was
      the major DNA methyltransferase expressed in gonocytes at 14-18 day postcoitum.
      Dnmt3L, which is necessary for spermatogenesis, was co-expressed in gonocytes at
      identical stages to Dnmt3a2. On the other hand, Dnmt3a was expressed not in germ
      cells but in the Sertoli cells and connective tissue cells that surround
      gonocytes and spermatogonia. Dnmt3b2, an isoform of Dnmt3b, was expressed faintly
      but significantly in gonocytes at 16 days postcoitum, and increased in
      spermatogonia at 4 and 6 days postpartum. The expression of Dnmt3a2, Dnmt3L, and
      Dnmt3b2 at 14-18 dpc was confirmed by reverse transcriptase-coupled polymerase
      chain reaction amplification and nucleotide sequencing of the amplified
      fragments. The results strongly suggest that Dnmt3a2 and Dnmt3L are responsible
      for the global DNA methylation in mouse male germ cells.

PMID- 15567720
TI  - The developmental expression of two Xenopus laevis steel homologues, Xsl-1 and
      Xsl-2.
AB  - We have investigated the expression patterns of two Xenopus laevis genes with
      similarity to mouse steel (sl) using whole-mount in situ hybridization. Areas of
      overlapping expression include the epidermis, stomodeum, proctodeum, and otic
      placodes. Xsl-1 is specifically expressed in the pronephros, neural tube, gil
      arches, and a superficial region of the somite, while Xsl-2 is in the ganglion
      and facial nerve projecting to visceral arch 3, the mandibular arch, and the
      clefts of anterior somites. Thus, both transcripts exhibit partially overlapping
      expression patterns, but their tissue distribution differs significantly from
      that of sl expression in the mouse and chicken.

PMID- 15567721
TI  - High expression during neurogenesis but not mammogenesis of a murine homologue of
      the Deleted in Breast Cancer2/Rhobtb2 tumor suppressor.
AB  - Deleted in Breast Cancer-2, Dbc2, identified as a candidate tumor suppressor gene
      for breast cancer and other human malignancies, is a member of a novel gene
      family encoding putative small GTPases designated as Rhobtb. In this report, we
      describe the spatio-temporal expression of mDbc2/Rhobtb2 mRNA during mammary
      gland development and embryogenesis in the mouse. We have first determined that
      mDbc2/Rhobtb2 transcripts are expressed at low, but seemingly constant levels
      during mammopoiesis. Secondly, we have found that mDbc2/Rhobtb2 is expressed
      highly and specifically in the central and peripheral nervous systems during
      mouse embryogenesis. While our results do not reveal any connection between
      elevated expression of mDbc2/Rhobtb2 and a specific stage of mammary gland
      development, they strongly support a role for this gene during development of the
      nervous system.

PMID- 15567722
TI  - The expression of AmphiMdp during amphioxus early development.
AB  - We report here the expression of AmphiMdp in embryos and larvae. Faint AmphiMdp
      transcripts were first detected in the mesendoderm at the mid-gastrula stage and
      later in the somites of the early neurula. Expression remained in somites
      throughout the neurula and early larval stages and then disappeared from the
      somites starting with the most anterior somite and progressing posteriorly. At
      the 48-h larval stage, transcripts were detected in the developing tail bud. No
      transcripts were detectable in the somites of the 72-h larva. The result suggests
      that AmphiMdp is involved in myogenesis in amphioxus.

PMID- 15567723
TI  - Restricted germ cell expression of a gene encoding a novel mammalian HORMA domain
      containing protein.
AB  - HORMA-domain containing proteins are involved in cell cycle regulation by
      interactions with chromatin. Through an in silico subtractive screen for mouse
      genes preferentially expressed in newborn ovaries, we identified a gene that
      would encode a novel mammalian HORMA domain-containing protein termed Newborn
      Ovary HORMA protein (Nohma). Reverse transcription polymerase chain reaction and
      Northern blot analysis have demonstrated a 1.7 kb transcript that is expressed
      exclusively in germ cells in both male and female mouse gonads. Nohma expression
      can be detected postnatally in male, and prenatally in female gonads, but shows a
      sexually dimorphic expression in adult gonads. The Nohma transcript is abundant
      in the adult testis but limited in the adult ovary. The mouse Nohma gene is
      comprised of 15 exons and maps to chromosome 3. A human ortholog was also
      identified. The expression pattern of Nohma suggests that it may be a critical
      regulatory protein in germ cell meiosis.

PMID- 15567724
TI  - Identification and expression pattern of mago nashi during zebrafish development.
AB  - In a search for zebrafish genes expressed during early stages of development, we
      have identified two ESTs encoding proteins related to Drosophila mago nashi.
      Zebrafish mago nashi codes for a small protein with no clearly identified
      functional domains, and which is highly conserved during evolution. This paper
      describes the identification and a detailed gene expression analysis of zebrafish
      mago nashi during development. Our results demonstrate that mago nashi encodes a
      maternal transcript detected in both blastomeres and yolk cell at the 1-2 cell
      stages, and in the blastoderm during segmentation. We show that a putative
      microtubule-mediated transport of mago nashi mRNA from the vegetal hemisphere
      into animal blastomeres determines the localization of the transcript in the
      animal pole, immediately after fertilization. Furthermore, the microtubule array
      contained into the yolk cell seems to be responsible for the high level of mago
      nashi transcript detected in the central blastomeres at the 8-16 cell stages.
      Zygotic mago nashi is expressed into the dorsal-marginal region during
      gastrulation, and starting from somitogenesis to 24 hpf, the expression domain
      becomes progressively restricted to the developing neural tube and paraxial
      structures, and ventrally to the pronephric ducts.

PMID- 15567725
TI  - Expression of the zebrafish Staufen gene in the embryo and adult.
AB  - Staufen, a double stranded RNA binding protein, has been shown to be involved in
      creating and maintaining cellular asymmetry in the Drosophila oocyte, neuroblast,
      and mammalian neuron. Staufen binds to the 3' UTR of specific mRNAs and acts in
      their localization and anchoring to various subcellular domains. Staufen's
      molecular interactions during development have been limited to investigations in
      Drosophila melanogaster. Since a vertebrate Staufen has not been studied in a
      developmental system, the aim of this study was to clone and characterize a
      staufen orthologue gene in the vertebrate developmental model, zebrafish. The
      zebrafish staufen-like sequence shows a 64% homology to the human staufen with a
      81.2% homology in the highly conserved double stranded RNA binding domain
      (dsRBDs). Staufen maps on the LN54 radiation hybrid panel to linkage group 6,
      16.25 cR from Z265 between fb22h06 and fi16e01. Northern blot and in situ
      hybridization showed that staufen is expressed both maternally and zygotically.
      Zygotically expressed staufen is localized to the developing nervous system and
      at 24 h is highly concentrated in the subventricular zone of the developing
      brain. Maternally expressed staufen is dispersed in the mature oocyte and early
      embryo. In the adult, staufen is expressed in specific brain nuclei, the testis,
      neurons and Leydig cells.

PMID- 15567726
TI  - Pathophysiology of syndromic combined pituitary hormone deficiency due to a LHX3
      defect in light of LHX3 and LHX4 expression during early human development.
AB  - The pathophysiology of combined pituitary hormone deficiency (CPHD) is just
      beginning to be elucidated, with mutations in genes encoding transcription
      factors expressed at different stages of pituitary development. Among them, the
      two closely related genes, LHX3 and LHX4, are believed to share redundant
      biological properties. The patients with a LHX3 mutation display a CPHD
      phenotype, associated with a rigid cervical spine. This latter feature, not
      reported in Lhx3-/- and Lhx4-/- mice nor in patients with a LHX4 defect, prompted
      us to study the molecular consequences of a previously identified LHX3 23-bp
      deletion and to determine the LHX3 and LHX4 expression patterns during early
      human development. This deletion, which results in the skipping of one coding
      exon, would lead to a protein with no transcriptional capability. Using in situ
      hybridization, we show that LHX3 and LHX4 are expressed in the developing human
      pituitary and along the rostro-caudal length of the spinal cord; here, both
      transcripts are detected in the ventral part giving rise to motorneurons and
      interneurons. However, whereas LHX3 is expressed at all stages studied, LHX4
      expression is transient, and, at 6 weeks of development, is stronger at the
      caudal than at the cervical level.

PMID- 15567727
TI  - Developmental expression pattern of D-ets4, the Drosophila homologue of human
      Pdef.
AB  - Primordial germ cells (PGCs) are the first cells specified in many organisms. In
      Drosophila, as in mammals, PGCs are formed at the posterior end outside of the
      embryonic proper. They are brought into the gut during gastrulation and then
      actively migrate through the gut epithelium into the mesoderm. They attach to the
      future gonadal mesoderm and coalesce, forming the gonads. Control of this
      migratory process is not yet completely understood. D-ets4 and its mammalian
      homologue Pdef are members of the evolutionarily conserved Ets family of
      transcription factors. Pdef has been shown to down-regulate the invasive and
      migratory potential of breast tumors. Our results show that the Drosophila D-ets4
      protein is specifically expressed in PGCs before the onset of migration and is
      lost in the migratory and post-migratory PGCs. We also show that D-ets4 is not
      involved in other migratory events such as border cell migration during
      oogenesis. It is, however, expressed strongly in the pre-stage 10 oocyte nuclei
      and modestly in larval tissues such as imaginal discs and salivary glands, but
      not in the brain.

PMID- 15567728
TI  - Expression of bmp2a and bmp2b in late-stage zebrafish median fin development.
AB  - Zebrafish bmp2a and bmp2b mRNA expression in the developing median fins (caudal,
      anal, and dorsal) of late-stage larvae (>5 days post-fertilization) was analyzed
      by reverse transcriptase-PCR (RT-PCR) and in situ hybridization. bmp2a is
      expressed in developing fin rays, while bmp2b is expressed in developing fin
      rays, hypertrophic chondrocytes, and in the zone of segmentation (ZS) in
      developing anal and dorsal fin radials. This latter pattern of bmp2b expression
      in the ZS mirrors tetrapod bmp2 expression in developing joints. Additionally,
      both genes are expressed in neural and hemal arches and spines. bmp2a is strongly
      expressed in the lens; lens bmp2b expression is detected only weakly via RT-PCR.

PMID- 15567729
TI  - Differential expression and imprinting status of Ins1 and Ins2 genes in
      extraembryonic tissues of laboratory mice.
AB  - There are two functional insulin genes in the mouse genome. The Ins2 gene is
      imprinted and expressed monoallelically from the paternal allele in the yolk sac.
      In the present study we have re-examined the imprinting status of Ins1. We found
      that Ins1 is not expressed in the yolk sac of several laboratory mouse strains.
      The asynchrony of replication at the wild type locus was significantly lower than
      at imprinted loci and was more similar to non-imprinted loci. Finally, we have
      taken the advantage of the Ins1(neo) allele created by homologous recombination
      to examine the allelic usage at this locus. We observed that the neo gene
      inserted at the Ins1 locus was expressed from both the paternally and the
      maternally transmitted allele. Therefore, the Ins1 gene does not share any of the
      basic properties of imprinted genes. On the basis of these data, we concluded
      that Ins1 locus is unlikely to be imprinted in common laboratory mice.

PMID- 15567730
TI  - Protection of the liver during partial hepatectomy.
AB  - BACKGROUND: Liver failure is the most common cause of mortality for patients
      undergoing partial hepatectomy. Given adequate liver function and remnant liver
      volume and absence of co-morbid illness, the cause of liver failure is frequently
      related to technical errors, which induces massive bleeding and ischemic damage
      to the liver remnant. DATA RESOURCES: From author's practice at Queen Mary
      Hospital, the University of Hong Kong. RESULTS: To avoid technical errors leading
      to liver ischemia and failure, adequate exposure, control of bleeding during
      liver transection, and planning of transection plane are important. Ultrasonic
      dissector is the best instrument in liver transection. Its careful use can reduce
      blood loss and help recognize the hepatic vein, the exposure of which serves as
      an important landmark for a correct transection plane. Even without Pringle
      maneuver, minimum bleeding during transection could be achieved. CONCLUSION:
      Protection of the liver remnant is important to patient survival after partial
      hepatectomy. It is achieved by meticulous surgical techniques that reduce
      bleeding to a minimum.

PMID- 15567731
TI  - Downstaging followed by resection plays a role in improving prognosis of
      unresectable hepatocellular carcinoma.
AB  - BACKGROUND: Curable outcome of unresectable hepatocellular carcinoma (HCC) was
      seldom encountered in the past. This study was designed to assess the role of
      downstaging followed by resection (downstaging-resection) in the improvement of
      prognosis of unresectable HCC. METHODS: During the period of 1958-2003, a total
      of 1085 patients were verified surgically to be unresectable. Of these patients,
      139 received downstaging-resection, with a rate of 84.2% for coexisting cirrhosis
      and a median tumor diameter of 11.1 cm. Resection of the right lobe, hepatic
      hilum and bilateral cancer accounted for 97.8% of the patients. Downstaging
      including hepatic artery ligation (HAL)+hepatic artery chemo-infusion (HAI) was
      performed in 65.5% of the patients, HAL+HAI+radiotherapy/radioimmunotherapy in
      29.5%, and HAL or HAI alone in 5.0%. Retrospective analysis was made of the
      survival of patients with unresectable HCC, downstaging-resection rate and
      treatment pattern. RESULTS: In the 139 patients with downstaging-resection, the
      median interval between the first and second operation was 7.2 months and the 5
      year survival rate calculated from the first operation was 48.7%. In the 1085
      patients with unresectable HCC, their 5-year survival was 0% in the period of
      1958-1973, 11.5% in the period of 1974-1988 and 19.3% in the period of 1989-2003.
      These figures were correlated with the increasing downstaging-resection rate from
      0%, 9.0% to 15.6%, and the increasing percentage of triple or double combination
      treatment from 32.2%, 60.4% to 69.7%. The 5-year survival in triple treatment
      group was 24.9%, double treatment 15.2%, and single treatment only 10.9%, which
      was also correlated with the downstaging-resection rate of 34.6%, 16.2% and 1.8%
      respectively. CONCLUSIONS: Downstaging-resection plays a role in improving
      prognosis of unresectable HCC. Triple and double treatments provide a higher
      downstaging-resection rate and may result in better prognosis.

PMID- 15567732
TI  - Liver transplantation for patients with hepatic alveolar echinococcosis in late
      stage.
AB  - BACKGROUND: Failed surgical treatment and multiple operations often lead to liver
      failure and make it difficult to be treated by traditional methods. Liver
      transplantation may be the ideal and the last choice. In this study we tried to
      explore the indication of liver transplantation for hepatic alveolar
      echinococcosis (HAE) and the improvement of intraoperative treatment. METHODS:
      Five patients who had received liver transplantation of hepatic alveolar
      echinococcosis in our hospital from 1999 through 2003 were analyzed
      retrospectively. RESULTS: All the patients (3 were male and 2 female) were in
      late stage of hepatic alveolar echinococcosis. During orthotopic liver
      transplantation(OLT), 4 patients underwent veno-venous bypass, 3 were subjected
      to veno-venous bypass prior to the mobilization of the liver, and 2 received
      placement of T tube in the bile duct. In all the patients treated successfully by
      OLT, 4 recovered, and 1 died of severe infection and acute rejection after
      operation. T tube fell off in one patient. Postoperatively, pathological
      diagnosis verified hepatic alveolar echinococcosis. Four patients were followed
      up to the present, showing a good life quality and work capacity. CONCLUSIONS:
      Hepatic alveolar echinococcosis in late stage can be considered as one of the
      indications of liver transplantation. Technique of veno-venous bypass prior to
      the mobilization of the liver could decrease operative time and bleeding. Early
      diagnosis and treatment of the disease ensures a better prognosis.

PMID- 15567733
TI  - Lamivudine in prevention and treatment of recurrent HBV after liver
      transplantation.
AB  - BACKGROUND: Chronic hepatitis B virus infection is one of the major causes of
      liver cirrhosis worldwide, especially in Asia. Liver transplantation for the end
      stage liver disease with hepatitis B virus(HBV) is commonly complicated by the
      recurrence of HBV. The present study was designed to evaluate lamivudine in the
      prevention and treatment of recurrent HBV after liver transplantation. METHODS:
      Seventeen patients with HBV-related liver disease in a total of 41 patients have
      received liver transplantation at our hospital since 2001. All the patients were
      HBV positive before transplantation, 5 of them had acute liver failure.
      Artificial liver was used in 4 patients with acute liver failure. All of the
      patients received lamivudine at a dose of 100 mg/d after liver transplantation.
      Lamivudine and HBIg therapy were given to 3 patients. RESULTS: Liver
      transplantation was successfully performed in all 17 patients. Three patients
      died of complications 3-6 months after the transplantation. One patient withdraw
      from lamivudine therapy and died of liver failure at 14 months after the
      transplantation. Thirteen patients were followed up from 6 to 18 months. Two
      viremic patients had HBV recurrence shortly after the transplantation. Two
      viremic patients who had received HBIg and lamivudine after the transplantation
      had no evidence of HBV recurrence. CONCLUSIONS: Lamivudine therapy is effective
      in preventing HBV recurrence after liver transplantation. The recurrence of HBV
      is closely related to HBV DNA status before liver transplantation.

PMID- 15567734
TI  - Molecular adsorbent recycling system in treating patients with acute liver
      failure: a bridge to liver transplantation.
AB  - BACKGROUND: Acute liver failure is still a life-threatening disease although it
      can be treated by liver transplantation. This study was conducted to assess the
      molecular adsorbent recycling system (MARS), which may bridge acute liver failure
      patients to liver transplantation. METHODS: Biochemical indexes and other
      clinical data were analyzed of 8 patients with acute liver failure, who had been
      treated by MARS for 34 times and subsequent Piggyback liver transplantation.
      RESULTS: After treatment with MARS, the levels of transaminase and total
      bilirubin decreased markedly, but coagulation function remained unimproved. All
      patients survived and discharged from the hospital. CONCLUSION: MARS is effective
      in bridging patients with acute liver failure to liver transplantation.

PMID- 15567735
TI  - Construction and biological activities of human tPA eukaryotic expression
      plasmid.
AB  - BACKGROUND: Tissue-type plasminogen activator(tPA), which is highly efficient and
      specific in resolution of thrombus, could significantly improve the survival rate
      and life-quality of the patients with thrombosis. This study was designed to
      clone human tPA gene, construct eukaryotic expression plasmid pcDNA3.1(+)/tPA,
      and evaluate their biological activities. METHODS: The tPA gene was obtained from
      dead human heart tissue with reverse transcriptase-polymerase chain reaction (RT
      PCR). It was cloned to eukaryotic expression plasmid pcDNA3.1(+) by recombination
      strategy. The eukaryotic expression plasmid pcDNA3.1(+)/tPA was identified by
      restriction enzyme digestion and sequenced. The pcDNA3.1(+)/tPA was transfected
      into vascular smooth muscle cell (VSMC) by using lipofection. The tPA expression
      level was detected by Northern blot and dot blot, and the protein biological
      activities of tPA were detected by the fibrin plate technique. RESULTS: The tPA
      gene was cloned and pcDNA3.1(+)/tPA was constructed. The tPA expression levels of
      mRNA and protein were highly increased after pcDNA3.1(+)/tPA transfected into
      VSMC, and the expression of tPA protein showed evident biological activities.
      CONCLUSIONS: The present study has laid a foundation for further animal
      experiment in treating thrombus in transplanted organ by tPA gene transfection.

PMID- 15567736
TI  - Small diameter H-graft porta-caval shunt performed at different stages of liver
      disease.
AB  - BACKGROUND: Partial porto-systemic shunts have been popularized because of
      reported low rate of mortality and morbidity (especially encephalopathy, liver
      failure and occlusion). To further investigate these assumptions, we
      retrospectively reviewed the results of partial porta-caval shunts performed at
      different stages of liver disease. METHODS: Twenty-nine cirrhotic patients
      underwent a partial porta-caval shunt with a ringed polytetrafluoroethylene
      interposition prosthesis of 8-mm (20 patients) or 10-mm (9 patients) in diameter.
      Pre and post-shunt porta-caval pressure was measured in all patients. Twelve
      patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%).
      Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively.
      Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval
      pressure gradient, reduced significantly using either 8- or 10-mm prosthesis. The
      overall early mortality and morbidity were 13.8% and 48% respectively. The early
      mortality and morbidity were different between patients of Child A and B when
      compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No
      patient re-bled early from varices. The overall late mortality and morbidity were
      40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8%
      of the two groups of patients respectively; variceal re-bleeding occurred in 4
      patients (16%). Encephalopathy occurred postoperatively in 5 patients (20%),
      acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at
      3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients
      of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate
      that partial porta-caval shunt with a small diameter interposition H-graft is an
      effective procedure for the treatment of variceal bleeding, as well as for the
      prevention of re-bleeding in patients of Child A and those of Child B, as an
      elective or emergency/urgency procedure, with a low rate of complications and
      encephalopathy. This technique could be used safely in patients with good liver
      function but they should be monitored closely because of the risk of shunt
      occlusion.

PMID- 15567737
TI  - Management of severe Budd-Chiari syndrome: report of 147 cases.
AB  - BACKGROUND: Budd-Chiari syndrome (BCS) is an uncommon disorder caused by the
      obstruction of hepatic venous outflow and/or the inferior vena cava. Major
      therapeutic approaches include operation and radiological intervention. This
      study was conducted to investigate the treatment of severe BCS. METHODS: The
      clinical data of 147 patients with severe BCS who had been treated at our
      hospital from November 1994 to December 2003 were retrospectively analyzed.
      RESULTS: One hundred twenty-one patients with BCS underwent surgery, including
      mesocaval C type shunt with artificial graft (82 patients), splenojugular shunt
      (37), mesojugular shunt (2), percutaneous transhepatic recanalization and
      dilatation and/or stent placement of the main hepatic vein (MHV) (12), and
      combined percutaneous transhepatic angioplasty (PTA) and stent placement of the
      inferior vena cava and mesocaval shunt (14). Follow-up for 6-108 months showed
      excellent results in 102 patients (69.4%), good results in 40 (27.2%), and 5
      deaths. CONCLUSION: Good results could be obtained in most of patients with BCS
      after different surgical treatments according to the pathological changes of the
      IVC and MHV.

PMID- 15567738
TI  - Diagnosis and surgical treatment of giant splenic artery aneurysms with portal
      hypertension: report of 4 cases.
AB  - BACKGROUND: Giant splenic artery aneurysm (GSAA) is a rare but clinically
      relevant disease. Its importance lies in potential rupture and hemorrhage. Early
      diagnosis and treatment before rupture of GSAA are crucial to GSAA patients
      especially to GSAA patients with portal hypertension(PHT). METHODS: Four patients
      of GSAA with PHT treated at our hospital from December 1999 to September 2001
      were retrospectively reviewed. RESULTS: GSAA was found in all patients with
      digital substracted angiography (DSA) and/or magnetic resonance angiography (MRA)
      before operation. Resection of GSAA and treatment of PHT were carried out
      successfully with no perioperative mortality. CONCLUSIONS: Patients with GSAA are
      apt to have PHT or segmental PHT because of suppression of the splenic vein or
      formation of aneurysm-portal vein fistula. Operation should be focused on GSAA,
      and PHT complications.

PMID- 15567739
TI  - Quality of life in patients with liver cancer after operation: a 2-year follow-up
      study.
AB  - BACKGROUND: Quality of life (QL) is a concept which reflects the physical,
      social, and emotional attitudes and behaviours of an individual. QL assessment is
      becoming increasingly recognised as an outcome and predictor for cancer patients.
      Although hepatectomy has been widely accepted as treatment of choice to offer a
      chance of cure for patients with liver cancer, little is known about the
      subjective clinical results after this operation. This prospective study was
      designed to evaluate the Pre- and postoperative quality of life in patients with
      liver cancer. METHODS: The quality of life of 36 consecutive patients was
      measured using gastrointestinal quality of life index (GQLI) regularly 2 years
      after the operation, starting with a preoperative measurement. RESULTS: The score
      of mean preoperative GQLI was 106+/-13 points, and it was reduced significantly 2
      10 weeks after the operation (86-98) (P<0.05-0.001). The quality of life
      recovered gradually. The GQLI score was 101+/-21 points 4 months after operation
      and increased to the preoperative level (P>0.05). In the patients who survived
      more than 9 months, the GQLI score was higher than that before the operation.
      Major hepatectomy (lobectomy and combined segmentectomy) reduced the GQLI score
      more evidently than did minor hepatectomy (simple segmentectomy) in 2-5 weeks
      after the operation (P<0.05). The age and preoperative liver function of the
      patients played an important role in the recovery of the quality of life in the
      early postoperative stage (P<0.05). The patients with tumor recurrence showed a
      continuous decrease of the quality of life (P<0.05-0.001). CONCLUSIONS: The
      assessment of the quality of life is meaningful for patients with liver cancer.
      Tumor recurrence, poor liver function and major operation are the most important
      factors for reducing the quality of life. Hepatic resection is justified by its
      effects on the survival and the quality of life of the patients.

PMID- 15567740
TI  - Triplex operation for portal hypertension with esophageal variceal bleeding:
      report of 140 cases.
AB  - BACKGROUND: Portal hypertension is a common disease. The surgical therapy of this
      disease focuses on the resultant upper digestive tract bleeding, which can
      imperil patients' life directly. This study was to evaluate the effect of triplex
      operation (mesocaval C shunt with artificial graft, ligation of the coronary vein
      and splenic artery) on portal hypertension and its associated upper digestive
      tract bleeding. METHODS: A retrospective study was made on clinical data of 140
      patients undergoing triplex operation, who had suffered from portal hypertension
      and upper digestive tract bleeding. RESULTS: Postoperative portal pressure was 25
      43 cmH2O(preoperative portal pressure 27-45 cmH2O) with the average reduction of
      10 cmH2O. One patient (0.7%) died of cerebrovascular disease. Five patients
      (3.5%) suffered from mild hepatic encephalopathy, which was ameliorated through
      conservative treatment. Lymphatic fistula occurred in 3 patients (2.1%) who
      recovered without treatment 5, 10 days and 3 months after operation respectively.
      One hundred patients were followed up for 1 month to 6 years without recurrent
      hemorrhage or hepatic encephalopathy. Hypersplenism and ascites disappeared in 70
      patients (70%) and 80 patients (80%) respectively. A significant reduction of
      ascites was seen in 12 patients(12%). The artificial vessels remained unblocking
      detected by B type ultrasonography and Doppler sonography in 95 patients(95%).
      CONCLUSION: Triplex operation is suitable for patients with the following portal
      hypertensions: portal hypertension caused by simple occlusion of the hepatic vein
      (a pathological type of Budd-Chiari syndrome); thrombosis of the portal vein or
      prehepatic portal hypertension because of cavernous transformation; intrahepatic
      portal hypertension with rebleeding after splenectomy or non-operation, and those
      patients with liver function in grade A or B according to the Child-Pugh
      classification.

PMID- 15567741
TI  - Analysis of causes for liver function deterioration in patients with HIV/HCV co
      infection.
AB  - BACKGROUND: Co-infection of hepatitis C virus (HCV) and human immunodeficiency
      virus type 1 (HIV-1) is common in hemophiliacs and drug abusers. To assess the
      interaction between HIV and HCV disease progression, we examined 82 HIV/HCV co
      infection patients and 62 HCV infection patients. METHODS: Liver function,
      pathological changes, infection duration, immune function and qualitative HCV-RNA
      and HCV antibody were compared retrospectively between the two groups of
      patients. RESULTS: Fourty-eight patients (58.5%) in the HIV/HCV co-infection
      group and 53 patients (85.5%) in the HCV infection group showed abnormal liver
      function. No significant difference was observed in inflammation and fibrosis in
      the two groups (P=0.187, 0.954). However, liver abnormality in the patients with
      HIV/HCV co-infection appeared 8 years earlier than in those with HCV infection
      alone (P<0.001). As to immune function, the counts of CD+4 T and CD+8 T in the
      HIV/HCV group were (226.35+/-173.49)X10(6)/L and (914.40+/-448.28)X10(6)/L,
      whereas in the HCV group they were (752.31+/-251.69)X10(6)/L and (529.01+/
      170.67)X10(6)/L respectively. The difference in the two groups was highly
      significant (P<0.001; P<0.001). The ratio of the number of people with both HCV
      RNA and HCV antibody positive to the number of HCV-RNA positive and HCV antibody
      negative in the HIV/HCV group was 52:9, whereas in the HCV group it was 44:1
      (P=0.043). CONCLUSION: HIV/HCV co-infection can accelerate deterioration of
      hepatitis C, which may be due to the effect of HIV on cellular immunity and
      humoral immunity of the body.

PMID- 15567742
TI  - Effects of cell cycle on telomerase activity and on hepatitis B virus replication
      in HepG2 2.2.15 cells.
AB  - BACKGROUND: It has been shown that telomerase activity and hepatitis B virus
      (HBV) replication are closely associated with cell cycle. This study aimed to
      further investigate the effects of cell cycle on telomerase activity and on HBV
      replication. METHODS: Human hepatoma cells transfected with HBV DNA (HepG2 2.2.15
      cell line) were treated respectively with serum deprivation, all-trans retinoic
      acid (RA), dimethyl sulfoxide (DMSO), or sodium butyrate. The cell cycle of HepG2
      2.2.15 cells was analyzed by flow cytometry. The telomerase activities of the
      cells were detected by TRAP-PCR-ELISA. HBV DNA in culture medium was assayed by a
      fluorescent quantitative PCR assay and a semiquantitative dot blot hybridization
      technique. HBsAg and HBeAg in culture media were quantitatively examined by an
      ELISA assay. RESULTS: Treatments with serum deprivation, RA, DMSO, or sodium
      butyrate inhibited the proliferation of HepG2 2.2.15 cells and led to cell arrest
      in the G0/G1 phase of cell cycle. The percentage of the G0/G1 phase in the groups
      of sodium butyrate, DMSO, RA and serum-free was 85.2%, 71.9%, 68.3% and 65.2%,
      respectively, but in the control group, 43.1% (P<0.01). The activities of
      telomerase of the cells were also significantly inhibited by 82.8%, 74.6%, 76.1%
      and 69.4% respectively. In addition, HBV replication of the HepG2 2.2.15 cells
      remarkably increased as shown by the contents of HBV DNA, HBsAg and HBeAg in the
      culture media of the cells treated with sodium butyrate, DMSO, RA or serum
      deprivation (P<0.01). The amounts of HBV DNA in the groups of sodium butyrate,
      DMSO, RA, serum deprivation and control were 6.7X10(6), 4.8X10(6), 4.4X10(6),
      5.1X10(6) and 1.2X10(6) copies/ml, respectively (P<0.01). Telomerase was
      expressed mainly in the cells in S phase. HBV replication increased in quiescent
      cells (G0/G1 phase), and decreased in proliferating phase (S phase). CONCLUSION:
      The current data approve that HBV replication is associated with the cellular
      proliferative activity.

PMID- 15567743
TI  - Integrin beta1 mediates hepatocellular carcinoma cells chemotaxis to laminin.
AB  - BACKGROUND: Chemotaxis is an important step during the invasion of carcinoma
      cells. And integrins are most important receptors mediating interaction between
      cells and extracellular matrix (ECM). This study was designed to study integrin
      beta1 mediating chemotaxis of hepatocellular carcinoma (HCC) cells to
      laminin(LN). METHODS: A micropipette technique was adopted to investigate the
      effect of blockade of integrin beta1 on pseudopod protrusion of HCC cells in
      response to LN stimulation. Chemotactic pseudopod protrusion of a HCC cell was
      evaluated using a dual-pipette set-up, in which two pipettes filled with LN
      solution were positioned in close contact with the same cell, and pseudopod
      protrusion into each pipette was viewed dynamically and recorded with a tape
      recorder. The lengths of pseudopods were measured and plotted against time to
      obtain a pseudopod growth curve. The integrin beta1 subunit on the surfaces of
      HCC cells were analyzed by flow cytometry. RESULTS: In dual pipette chemotaxis
      experiment, when the two pipettes were filled with LN(50 microg/ml, 200
      microg/ml), pseudopods extended from the HCC cell into each of the pipettes
      nearly symmetrically, ie, with nearly identical maximum pseudopod length and
      similar pseudopod growth curves. Upon addition of anti-CD29 (20 microg/ml) to one
      of the pipettes, pseudopod protrusion was blocked nearly completely while
      protrusion into the opposite pipette became more evidently, with a larger maximum
      length. Expression of integrin beta1 was up to 95.78% to cells chosen in the
      experiment. CONCLUSION: Integrin beta1 subunit was an important constituent
      receptor subunit for mediating chemotactic pseudopod protrusion of HCC cell to
      LN.

PMID- 15567744
TI  - Inhibitory effects of antisense oligodeoxynucleotide on expression of vascular
      endothelia growth factor by human hepatocarcinoma cells.
AB  - BACKGROUND: It is widely recognized that the growth of solid tumor depends on
      angiogenesis. Vascular endothelia growth factor (VEGF) is an endothelial cell
      specific mitogen that promotes angiogenesis in solid tumor. Inhibition of
      angiogenesis is considered a promising approach for cancer therapy, and
      treatments including administration of antisense drugs and RNA interference for
      the VEGF gene are geared to the suppression of tumor angiogenesis. METHODS: As a
      new approach for gene therapy of hepatocellular carcinoma (HCC), four groups of
      antisense oligodeoxynucleotide (ASODN) (A-Cap, A-AUG, A-UGA and A-Exon-3) were
      used to block the expression of VEGF, then VEGF mRNA and protein were detected by
      RT-PCR and Western blot. RESULTS: After treatment with ASODN, the relative VEGF
      mRNA levels of A-Cap, A-AUG, A-UGA, and A-Exon-3 were decreased significantly to
      (32+/-9)%, (63+/-1)%, (86+/-3)%, and (70+/-5)%, respectively(F=64.18, P<0.001).
      The relative VEGF protein levels of A-Cap, A-AUG, A-UGA and A-Exon-3 were
      decreased significantly to (41+/-5)%, (59+/-3)%, (88+/-7)%, and (79+/-9)%
      respectively (F=60.64, P<0.001). CONCLUSIONS: Among the four ASODNs, the ASODN
      for Cap structure showed the strongest inhibitory effect and that for A-UGA, the
      least (P<0.05 ). The inhibitory effect of ASODN on the expression of VEGF
      proteins was similar to that of VEGF mRNA expression.

PMID- 15567745
TI  - Effects of Dan-Shao-Hua-Xian on the expression of collagen type I and III in rats
      with hepatic fibrosis.
AB  - BACKGROUND: Hepatic fibrosis is the common pathological change in various chronic
      liver diseases, and its major cause is the imbalance between the production and
      degradation of the extracellular matrix, which is mainly composed of collagens.
      Dan-Shao-Hua-Xian (DSHX) capsule, a traditional Chinese herbal compound, has
      shown marked preventive effects on hepatic fibrosis in rats in our previous
      studies. The present study was designed to further investigate its therapeutic
      actions on hepatic fibrosis in rats and its possible mechanisms. METHODS: Eighty
      male Wistar rats were randomly divided into normal control group, hepatic
      fibrosis group, non-DSHX-treated group, low-dose-treated group, and high-dose
      treated group. The rat models of hepatic fibrosis were established by
      subcutaneous injecton of CCl4, drinking alcohol, giving diet of hyperliprosis and
      hypoprotein for 8 weeks. The two DSHX-treated groups were treated respectively
      with low dose (0.5 g/kg) and high dose (1.0 g/kg) of DSHX capsule p.o. everyday
      for 8 weeks. At the end of the experiment, liver indexes were calculated in each
      group in addition to the levels of the serum hyaluronic acid and alanine
      aminotransferase. Their degree of hepatic fibrosis and urinary excretion of
      hydroxyproline and expression of collagen I, III were detected. RESULTS:
      Comparison of the indexes of the hepatic fibrosis group and non-DSHX-treated
      group revealed that the liver indexes, levels of serum hyaluronic acid and
      alanine aminotransferase, and stage of hepatic fibrosis were all significantly
      reduced in the two DSHX treated groups. The urinary excretion of hydroxyproline
      was increased and the expression of collagen I and III in liver tissue was
      lessened. These alterations were more obviously observed in the high-dose-treated
      group. CONCLUSION: DSHX capsule has certain therapeutic effect on hepatic
      fibrosis in rats.

PMID- 15567746
TI  - Abnormal expression of hepatoma-derived gamma-glutamyltransferase subtyping and
      its early alteration for carcinogenesis of hepatocytes.
AB  - BACKGROUND: Although the hepatoma-specific band of gamma-glutamyltransferase
      (GGT) is a highly sensitive marker in diagnosis of hepatocellular carcinoma, the
      kinetic expression and the early alterations of GGT in the development of
      hepatoma remain unclear. In this study, we investigated the expression and the
      alterations of GGT multiple molecular forms in hepatotumorigenesis. METHODS: The
      expression of GGT in a chemically induced hepatocarcinogenesis model was examined
      by giving 0.05% of 2-fluoenylacetamide in diet for 12 weeks. The expression
      levels of total RNA and GGT, and the changes of liver pathology, GGT multiple
      molecular forms and sugar-chain heterogeneity were investigated at the different
      stages of rat hepatoma development. RESULTS: Pathological examination and
      biochemical analysis found that liver GGT was over-expressed and secreted into
      blood during canceration. Serum total GGT and liver GGT specific activities
      (IU/g) including soluble and membrane-combined GGT were significantly higher
      (P<0.05) in experimental groups than those in control group, respectively. A
      highly positive correlation was found between total GGT activities and total RNA
      levels (r=0.90, P<0.05) of the liver. Both were higher six weeks later than
      before. Con A-non-reactive-GGT was increased consistantly during the development
      of rat hepatoma. GGT multiple molecular forms in the liver and sera of
      experimental rats showed that fetal liver-type GGT bands were associated with the
      development of hepatoma. CONCLUSIONS: Fetal liver-type GGT in sera and the liver
      of rats is closely related to hepatotumorigenesis. It can be used as a sensitive
      enzymatic marker for the early diagnosis of liver cancer.

PMID- 15567747
TI  - Effects of different infusion volumes on hemodynamics of portal hypertension
      canines after hemorrhagic shock.
AB  - BACKGROUND: Portal hypertension (PHT) with upper gastrointestinal hemorrhage as
      its chief complication is a very common disease with great harm to humans. The
      effects of infusion volume, speed, and type on hemodynamics in case of cirrhosis,
      PHT esophageal variceal bleeding, and their mechanism should be clarified. This
      study was designed to assess the effects of different infusion volumes on
      hemodynamics of PHT canines after hemorrhagic shock (HS). METHODS: PHT canine
      models were made by chronic embolization via coarctating half of the main portal
      vein with silk suture. Two weeks later, the models were subjected to hemorrhagic
      shock by quick femoral artery venesection. The canines were divided into two
      groups to resuscitate: one to receive a large volume of infusion (n=6) (large
      volume infusion group) and the other to receive a small volume of infusion (n=6)
      (small volume infusion group). Hemodynamic indexes of PHT canines after HS and
      infusion were observed closely. RESULTS: The PHT canines showed a series of
      hemodynamical changes in hemorrhagic shock stage, which aggravated hemodynamical
      disorder in PHT. After quick infusion, mean arterial pressure (MAP), inferior
      vena cava pressure (IVCP), portal venous pressure (PVP), portal vein pressure
      gradient (PVPG), portal vein blood flow (PVBF), hepatic artery blood flow (HABF)
      and hepatic blood flow (HBF) increased significantly. These indexes in the large
      volume infusion group were higher than those in the small volume infusion group.
      Portal vascular resistance (PVR), splanchnic vascular resistance (SVR), hepatic
      arterial resistance (HAR) decreased significantly, but PVP, PVPG, PVBF, HABF and
      HBF showed a rebounding increase above the baseline values in the large volume
      infusion group. The changes of PVP, PVPG, PVBF, HABF and HBF were in parallel
      with those of MAP and inferior vena cava pressure (IVCP), without a rebounding
      increase in the small volume infusion group. In the large volume infusion group
      PVPG increased earlier and more significantly than did PVP; moreover PVPG
      exceeded the baseline by 13%, making the possibility of rebleeding great. In the
      small volume infusion group, PVPG was lower than the baseline by more than 22%,
      indicating a small possibility of rebleeding. SVR and HAR were lower in the large
      volume infusion group. PVP, PVPG, PVBF, HABF and HBF were positively correlated
      with accumulated volume of vein infusion. PVR showed a positive correlation with
      accumulated volume of vein infusion in the small volume infusion group. HAR was
      negatively correlated with accumulated volume of vein infusion in the large
      volume infusion group. CONCLUSIONS: PHT canines after HS, resuscitated by vein
      infusion, may show a rebounding increase of PVP, PVPG, PVBF, HABF and HBF above
      the baseline values in the large volume infusion group but not in the small
      volume infusion group. A large volume infusion causes PVP, PVPG, PVBF, HABF and
      HBF to increase higher than does a small volume infusion.

PMID- 15567748
TI  - Effects of tea polyphenols on hepatic fibrosis in rats with alcoholic liver
      disease.
AB  - BACKGROUND: As an anti-oxidation agent, tea polyphenols may have the effect of
      anti-fibrosis. This study was designed to observe the effect of tea polyphenols
      on hepatic fibrosis in rats with alcoholic liver disease and to explore the
      related mechanisms. METHODS: Sixty healthy Sprague-Dawley rats were divided
      randomly into normal control group, single alcohol group, and three alcohol
      groups given different doses of tea polyphenols. Alcohol or isovolumic normal
      saline and corresponding doses of tea polyphenols were given daily to the rats
      separately. The rats were sacrificed at the end of the 24th week. Masson staining
      was performed to observe liver fibrosis, serum endotoxin, and oxidant and anti
      oxidant activity. RESULTS: Hepatic fibrosis was less severe in the rats of the
      alcohol groups given tea polyphenols than in the single alcohol group. Tea
      polyphenols increased the serum anti-oxidant capacity and decreased the endotoxin
      level. CONCLUSION: Tea polyphenols show anti-fibrosis effect in rats with
      alcoholic liver disease, and the mechanism may be related to the clearance of
      overall oxidant and decrease of the endotoxin level.

PMID- 15567749
TI  - Efficacy of intra-tumor injection of Kang-Lai-Te in treating transplanted
      hepatoma in rats.
AB  - BACKGROUND: Non-operative therapy takes an important position in comprehensive
      therapy of liver cancer. Despite some effects by using ethanol, acetic acid and
      heat saline for intra-tumor injection in the treatment of liver cancer, it is
      difficult to attain a complete cure but bring about injury to the liver to some
      extent. Hence, searching for other drugs for the local treatment of liver tumor
      is an important option. This study was designed to set up rat models of
      transplanted liver cancer, intra-tumor injection of Kang-Lai-Te (KLT), and
      negative control (saline) and positive control (ethanol). The effect of intra
      tumor injection of KLT in treating transplanted hepatoma in rats and its
      advantages and disadvantages were assessed and the possibility of its use in
      treating patients with liver cancer was evaluated. METHODS: Forty rats were
      divided into 4 groups (G1, G2, G3 and G4, 10 rats in each group). Different drugs
      were injected into their implanted hepatoma (G1 with 0.2 ml saline as control, G2
      with 10 mg KLT, G3 with 20 mg KLT, G4 with 0.2 ml ethanol). After 3 and 8 days,
      the hepatoma volume (HV), the serum levels of albumin, alanine
      aminotransferase(ALT), aspartate aminotransferase alkaline phosphatase(ALP) and
      creatinine, as well as the expression of proliferation cell nuclear antigen(PCNA)
      in hepatoma were detected. RESULTS: After 3 days, the HVs were smaller in G3 and
      G4 than in G1 (P<0.05), the serum levels of albumin were higher in G2 and G3 than
      in G1 and G4 (P<0.05), the serum levels of ALT and AST were lower in G2 and G3
      than in G4 (P<0.05), the serum levels of ALP was lower in G2 and G3 than in G1
      and G4 (P<0.05),the PCNA labeling indexes (PCNA LI) were lower in G2 and G3 than
      in G1 and G4 (P<0.05). After 8 days, the HVs were smaller in G2, G3 and G4 than
      in G1 (P<0.05), and the differences of HVs among G2, G3 and G4 were not
      significant. The serum levels of ALP were lower in G1, G2 and G3 than in G4
      (P<0.05), and the PCNA LI were lower in G3 than in G1 and G4 (P<0.05).
      CONCLUSION: Intra-tumor injection of KLT into implanted hepatoma is evidently
      effective, but it is less effective than ethanol. The effect of KLT on liver
      function is markedly lower than that of ethanol.

PMID- 15567750
TI  - A modified rat model for hepatocellular carcinoma.
AB  - BACKGROUND: Rat hepatocellular carcinoma (HCC) model which has a high analogy to
      clinical liver cancer is of great value in understanding the pathogenesis and
      evolution of liver cancer, in searching effective anti-cancer treatments (drug,
      hepatectomy and liver transplantation), and designing cancer prevention
      strategies. In this study we established a modified rat model of hepatocellular
      carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats
      were fed with diethylnitrosamine (DENA) by three methods for evaluation of
      general conditions for 130 days: Doppler ultrasonographic measurement, laparotomy
      and histopathological examination. RESULTS: No rat died in control group (group
      A) and modified DENA-induction-HCC group(group C), but 6 deaths in classical DENA
      induction-HCC group (group B) (survival rate 80%). All survived rats in groups B
      and C developed diffusive hepatocellular carcinoma and liver cirrhosis. General
      appearance of rats in the group C was better than that in the group B.
      CONCLUSION: With good general conditions for surgery, the modified rat model for
      hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.

PMID- 15567751
TI  - Effect of all trans-retinoic acid on the secretion of IV collagenase.
AB  - BACKGROUND: Invasion and metastasis cause death of patients with liver cancer.
      Increased expression of matrix metalloproteinases (MMPs) is closely associated
      with tumor progression. Type IV collagen is the main structure protein of basilar
      membrane which is a natural barrier for inhibiting the metastasis of liver cancer
      cells. In this experiment, we used all trans-retinoic acid (ATRA) to inhibit
      collagenase type IV in order to protect the type IV collagen and basilar
      membrane, further to suppress the metastasis of hepatocellular carcinomas.
      METHODS: By the use of cell culture and experimental animal models, the influence
      of all trans-retinoic acid (ATRA) on the invasion of Hca-F liver cancer cells was
      studied in terms of adhesion capacity to artificial basilar membrane and
      production of collagenase type IV. RESULT: ATRA could inhibit the adhesion
      capacity and collagenase IV secretion of Hca-F cells in a dose-dependent manner.
      CONCLUSION: ATRA can exert multiple effects on the invasion of Hca-F cells.

PMID- 15567752
TI  - Diagnosis and treatment of polypoid lesions of the gallbladder: report of 194
      cases.
AB  - BACKGROUND: With the wide use of B-ultrasonography in recent years, the polypoid
      lesion of the gallbladder (PLG) has been one of the most common diseases detected
      in biliary surgery. This study was to investigate the diagnostic method and
      operative indications of PLG. METHODS: The clinical and pathological data of 194
      patients with PLG who had received operation at our hospital from January 1994 to
      September 2002 were analyzed retrospectively. Categorized data were analyzed by
      the chi-square test. RESULTS: All the patients received preoperative B
      ultrasonography. 185 of the 194 PLG patients were diagnosed as having cholecystic
      polyp, and 9 adenomas. Among the 42 patients who received CT, 6 showed early
      gallbladder cancer. Pathologically, cholesterol polyps were mostly multiple
      lesions (64.7%) with a mean diameter of 3.86+/-2.2 mm in 136 patients. Of 16
      patients with adenomas, 10 had a tumor diameter of more than 10 mm (62.5%). In 11
      patients with gallbladder carcinoma, 7 were accompanied with gallbladder stone
      (63.6%). In addition, inflammatory polyps and adenomyomas were found in 25 and 6
      patients respectively. CONCLUSIONS: B-ultrasonography is the most effective
      diagnostic method for detecting PLG. When large or irregular lesions are found,
      CT should be performed in order to avoid missing of gallbladder carcinoma.
      Operative indications for PLG include: a maximal tumor diameter of more than 10
      mm; an over 50-year-old patient with a widebase and a single polyp lesion; a wide
      base lesion or a lesion showing a tendency to enlargement; co-existing
      gallbladder stone or cholecystitis; a patient without other diseases but obvious
      clinical features and failure of general management; big or long pedicels or
      polyps at the neck of the gallbladder for preventing the empty of the gallbladder
      and a history of biliary colic; and PLG with irregularly thickened local
      gallbladder wall.

PMID- 15567753
TI  - Spinal cord injury and cholelithiasis.
AB  - BACKGROUND: Spinal cord injury (SCI) is found to be related to increased
      prevalence of gallstones and acute acalculous cholecystitis. In this study we
      assessed the prevalence of cholelithiasis in male patients with SCI and the
      correlation of cholelithiasis with age and weight of patients, level of injury,
      as well as severity and duration of SCI. METHODS: One hundred male SCI patients
      (58 patients rated ASIA A or B and 42 rated ASIA C or D) aged more than 20 years
      (average 46.5 years) suffered from a spinal cord injury for more than one year.
      One hundred male volunteers served as controls without SCI and biliary
      diseases(age range 20-68 years; average 42.6 years). The two groups were
      subjected to ultrasonography of the gallbladder and biliary tract. RESULTS: The
      prevalence of cholelithiasis in the group of SCI patients and the control group
      was 26% and 10% respectively. Significant differences in the prevalence of
      cholelithiasis were found between the normal controls and SCI patients and
      between high and low-level injury (P<0.01). But the differences were not
      statistically significant when correlating the presence of cholelithiasis with
      the age and weight of the patients, the duration of SCI, and the severity of
      spinal lesion(P>0.05). CONCLUSIONS: SCI represents a major risk factor for the
      development of cholelithiasis,especially in patients with high-level injury.
      Cholelithiasis in SCI patients is not related to their age and weight, the
      severity of spinal lesion, and the duration of spinal cord injury.

PMID- 15567754
TI  - The ratio of MMP-2 to TIMP-2 in hilar cholangiocarcinoma: a semi-quantitative
      study.
AB  - BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and
      poor survival. The aim of this study was to evaluate the roles of matrix
      metalloproteinases-2 (MMP-2) and its tissue inhibitor of metalloproteinase-2(TIMP
      2) in tumor invasion or as a prognostic factor in patients with human hilar
      cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were
      investigated in patients. Paraffinized tissue sections obtained from 50 patients
      with human hilar cholangiocarcinoma were analysed. The expressions of MMP-2 and
      TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus
      analysis software was used to semiquantitatively determine the ratio of MMP-2 to
      TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly
      associated with tumor hepatic invasion in patients with hilar cholangiocarcinoma.
      Significant differences in the ratio of MMP-2 to TIMP-2 between some pathologic
      factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP
      2 plays an essential role in tumor invasion and metastasis, while TIMP-2 is shown
      to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2
      may be a prognostic indicator for patients with hilar cholangiocarcinoma.

PMID- 15567755
TI  - Influence of norcantharidin on proliferation, proliferation-related gene proteins
      proliferating cell nuclear antigen and Ki-67 of human gallbladder carcinoma GBC
      SD cells.
AB  - BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with
      early metastasis, strong invasion and poor prognosis. Most patients with this
      disease are at the advanced and un-resectable stage and should be considered for
      palliative treatment such as chemotherapy and radiotherapy. Unfortunately,
      reports of chemotherapy and radiotherapy for gallbladder carcinoma are
      disappointing. We investigated the influence of norcantharidin (NCTD) on
      proliferation, proliferation-related gene proteins PCNA and Ki-67 of human
      gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human
      gallbladder carcinoma were cultured by the cell culture technique. The experiment
      was divided into NCTD group and control group. The tetrazolium-based colorimetric
      assay was used to evaluate cell growth. The streptavidin-biotin complex method
      was used to determine the expressions of proliferation-related gene proteins PCNA
      and Ki-67 of human gallbladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited
      the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a
      dose-and time-dependent manner, with the IC50 value of 56.18 microg/ml at 48
      hours. After treatment with NCTD, the expression of PCNA (0.932+/-0.031 vs.
      0.318+/-0.023, P<0.001) and Ki-67 (0.964+/-0.092 vs. 0.297+/-0.018, P<0.001)
      proteins were decreased significantly. CONCLUSION: NCTD inhibits the
      proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the
      expression of their proliferation-related gene proteins PCNA and Ki-67.

PMID- 15567756
TI  - Pancreatic encephalopathy in 24 patients with severe acute pancreatitis.
AB  - BACKGROUND: Pancreatic encephalopathy (PE), an unfamiliar complication of severe
      acute pancreatitis (SAP), is difficult to diagnose and treat, and it has a high
      mortality. The aim of this study was to investigate the manifestation,
      classification, mechanism and therapy of PE. METHODS: Of 132 patients with SAP
      treated at our hospital from March 1994 to March 2004, 24 patients complicated by
      PE were analyzed retrospectively. RESULTS: The causes of SAP were mostly biliary
      and alcoholic. Twenty-four patients (18.2%) were complicated by PE within 3 hours
      38 days(average 6.6 days)[21(87.5%) within 2 weeks, and 3(12.5%) after 2 weeks] .
      Eleven patients were male and 13 female, with an average of 47 years (range 25-72
      years). Excitement or restrain was the main manifestation. Nine patients (37.5%)
      received surgery and 15(62.5%) conservative treatment, with a mortality of
      11.1%(1/9) and 66.7%(10/15), respectively. CONCLUSIONS: PE occurs 2 weeks after
      SAP and is part of multiple organ failure (MOF). Some patients have PE in the
      late stage of SAP because of lack of VitB1 and nutrition. But PE can be prevented
      by prescribing adequate nutrition and VitB1 in the early stage of SAP.

PMID- 15567757
TI  - Pancreatoduodenectomy with vascular reconstruction in treating carcinoma of the
      pancreatic head.
AB  - BACKGROUND: The incidence of carcinoma of the pancreas is increasing in the
      world. Pancreatic carcinoma is characterized by early local extension to
      contiguous structures and metastases to regional lymph nodes and the liver. This
      study was conducted to increase the rate of pancreatoduodenectomy combined with
      vascular reconstruction. METHODS: Pancreatoduodenectomy with vascular
      reconstruction was performed for 79 patients at a number of hospitals in Fujian
      Province, Zhejiang Province, Shanghai and Xinjiang Uyghur Autonomous Region from
      April 1994 to December 2003. One of these patients also underwent right
      hemicolectomy; but all received through superior mesenteric vein (SMV)-portal
      vein (PV) reconstruction. The reconstructions of the superior mesenteric artery
      (SMA) and hepatic artery (HA) were performed in 4 patients, and reconstructions
      of the SMA or HA were carried out in 7 and 4 patients respectively. Partial
      reconstruction of the inferior vena cava (ICV) was done in 2 patients when the
      tumor was adhering to the wall of the inferior caval vein. RESULTS: Four patients
      died during the peri-operative period, with a mortality rate of 5%. No
      complications such as biliary or pancreatic fistulae or artificial blood vessel
      infection were noted. Histological examination showed one patient with
      neuroendocrine cancer and the other 78 patients with adenocarcinoma of the
      pancreatic head. Resected endothelia and vascular margins proved to be
      microscopically tumor-free. Follow-up for 3 months to 10 years for all except two
      patients showed 7 of the 9 patients who had undergone resection and
      reconstruction of the SMA and HA died 7 months or 4 years after operation and 37
      survived for over 3 years and 12 for more than 5 years. The rest are still under
      follow-up. CONCLUSION: Pancreatoduodenectomy with vascular reconstruction for
      carefully selected patients with carcinoma of the pancreatic head has proved to
      be a safe and reliable treatment, capable of raising the rates of tumor resection
      and survival.

PMID- 15567758
TI  - Spiral CT localization of pancreatic functioning islet cell tumors.
AB  - BACKGROUND: Surgeons are always concerned about the localization of pancreatic
      functioning islet cell tumor. If the tumor is accurately localized before
      operation, resection of the pancreatic body and tail without intention can be
      avoided. The purpose of this study was to evaluate spiral CT localization of
      pancreatic functioning islet cell tumors and CT techniques. METHODS: CT
      manifestations in 6 patients with clinically and pathologically proved pancreatic
      functioning islet cell tumors were analyzed retrospectively. RESULTS: In 4
      patients with insulinomas and 2 patients with glucagonomas, 5 were localized
      accurately by CT before surgery and 1 was detected retrospectively. The
      enhancement of tumors was greater than that of normal pancreas in arterial phase
      and pancreatic parenchymal phase. Four patients showed mild high-density and 2,
      iso-density in the portal venous phase. CONCLUSION: Spiral CT multi-phase
      enhanced scan with 1.5 ml/kg contrast agent and 2-5 mm slice width can localize
      functioning islet cell tumors accurately.

PMID- 15567759
TI  - Simultaneous pancreas-kidney transplantation with portal-enteric drainage: a case
      report.
AB  - BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) with portal
      enteric drainage is physiological effective in treatment of patients with
      diabetes mellitus complicated by end-stage renal disease. A case is reported with
      a review of our clinical experience. METHODS: A patient with type 2 diabetes
      complicated by renal failure was subjected to SPK transplantation with portal
      enteric drainage. Pancreaticoduodenal allograft procured from corpse was
      transplanted to recipient's right abdomen with donor's portal vein anastomosed to
      recipient's superior mesenteric vein. Donor's plastic pancreas artery was
      anastomosed to recipient's right common iliac artery and donor's duodenum
      anastomosed to recipient's jejunum. The kidney allograft was transplanted
      ectopically to the contralateral iliac fossa. Postoperative immunosuppression
      includes tacrolimus (TAC)/mycophenolate mofetil (MMF)-based regimen and
      methylprednisolone or prednisone. RESULTS: On the 5th postoperative day, the
      level of blood creatinine decreased from 590 micromol/L to normal. Daily urine
      volume was about 2500 ml. On the 18th postoperative day, insulin was given up,
      and the levels of fasting blood-glucose and after meal blood-glucose were kept
      normal. No acute rejection symptoms or other complications were observed except
      infection of Pseudomonas aeruginosa. CONCLUSION: Combined pancreas and kidney
      transplantation with portal-enteric drainage is a physiological effective
      treatment for diabetic patients with end-stage renal disease.

PMID- 15567760
TI  - Chronic liver fluke disease with dyspepsia: a case report.
AB  - BACKGROUND: Chronic liver fluke disease with dyspepsia is rarely seen clinically.
      In this study, we assessed the etiological factors, symptoms, physical signs and
      diadynamic methods in a case of chronic liver fluke disease with dyspepsia.
      METHODS: Physical examination, laboratory studies, ultrasonography and CT scan
      were performed before pathogen examination. The eggs of fluke found with the
      inverted sedimentation method were also observed under a microscopy. They were
      diagnosed as the eggs of Clonorchis sinensis. RESULTS: The patient was diagnosed
      as having chronic liver fluke disease, and his appetite recovered after three
      courses of treatment with praziquantel. CONCLUSION: Eating fresh fish and shrimp
      might cause liver fluke disease. The symptoms of this disease with dyspepsia can
      be anorexia, abdominal distention, bellyache, and loose stools.

PMID- 15567761
TI  - [Two-dimensional electrophoretic separation of subproteomes in adult rat
      hippocampal subregions after membrane protein enrichment with sequential
      extraction].
AB  - OBJECTIVE: To establish a method for analysis of the subproteomes following
      membrane protein enrichment, so as to investigate the differences in cytosolic
      and membrane protein/peptide contents among different hippocampal subregions
      (CA1, CA3 and dentate gyrus) of rats. METHODS: The hippocampal subregions were
      isolated by microdissection, and after membrane protein enrichment with protein
      solubility-based sequential sample extraction, subproteome profiling was
      accomplished using modified two-dimensional electrophoresis and silver staining
      method compatible with high-performance mass spectrometry, which displayed
      cytosolic or membrane proteins/peptides separately. The efficacy of the
      electrophoresis was evaluated by image analyzing software. RESULTS: The membrane
      proteins were enriched by 8 folds, and around 30% more spots were shown on the
      integrated dentate gyrus map than on the conventional map obtained by one-step
      protein extraction. Such improvement could also be seen in protein mapping of CA1
      and CA3 regions. CONCLUSION: When analyzing hippocampal subregions sequential
      extraction and two-dimensional electrophoresis more effectively separate and
      display enriched membrane protein/peptides, which may play important roles in
      such cellular events as signal transduction.

PMID- 15567762
TI  - [Determination of stachydrine and leonurine in Herba Leonuri by ion- pair
      reversed-phase high-performance liquid chromatography].
AB  - OBJECTIVE: To establish a high-performance liquid chromatography (HPLC) for
      determining stachydrine and leonurine contents in the crude drug of Yimu Cao, a
      Chinese motherwort herb(Herba Leonuri, the aerial part of Leonurus japonicus).
      METHODS: The sample was obtained from the crude drug by ultrasonic extraction
      with ethanol after decolorization with ethyl acetate. YMC-Park CN column (250.0
      mm x 4.6 mm) was used with the mobile phase for stachydrine of 0.00125 mol/L
      SDS:C2H5CN (90:10) at the flow rate of 1.5 ml/min with the wavelength for
      detection of 201.7 nm, and that for leonurine of 0.00125 mol/L SDS (containing
      0.05% HClO4):CH4OH(90:10) at the flow rate of 1 ml/min with the wavelength for
      detection of 282 nm. The sensitivity was 0.1 AUFs and the column temperature was
      20 degrees Celsius;. RESULTS: With the injection amount (mg) as the abscissa and
      the peak area as the ordinate, the regression equation of the calibration curve
      for stachydrine was Y=1,187.542 3X-168.9822, and that for leonurine was
      Y=5,202.654X-221.141 (r=0.9998) with the linearity scope of 2.5-12.5 mg,
      detective limit of 0.15 mg, and recovery of (99.03+/-2.744) %. The analysis of
      extracted drug samples from 18 regions indicated that the alkaloids contents in
      Yimu Cao varied significantly, i.e. stachydrine within a range of 0.1%-0.2% while
      leonurine content, which was much lower, within 0.01%-0.05%. In general, the
      alkaloid contents were higher in the drug produced in northern China than in
      those produced in southern China. L. japonicus and the variant L. japonicus
      albiflorus had total alkaloid contents around 0.3%, which was higher than the
      contents of other species. CONCLUSION: As a convenient and feasible means for
      determining the alkaloid contents in Yimu Cao, HPLC produces accurate and
      reliable results and can be more effective than the formerly used methods.

PMID- 15567763
TI  - [Therapeutic efficacy of hematopoietic stem cell transplantation in patients with
      chronic myelogenous leukemia].
AB  - OBJECTIVE: To evaluate the clineffects of autologous and allogeneic hematopoietic
      stem cell transplantation (HSCT) for chronic myelogenous leukemia (CML). METHODS:
      Fifty-seven patients with CML were treated by HSCT, including 8 patients treated
      with autologous transplantation in vivo and vitro purging minimal residual
      disease (MRD), 39 with related donor allogeneic HSCT (allo-HSCT), and 10 with
      unrelated donor allo-HSCT. For the conditioning regimen, total-body irradiation
      with cyclophosphamide (CTX) was given in 32 patients, modified BuCY protocol
      (hydroxyurea, busulfan, Ara-C, CTX) in 24 patients, and MACC protocol (melphalan,
      Ara-C, CTX and lomustine) in one patient. Cyclosporine (CsA) and methotrexate
      (MTX) were used in patients with related donor allo-HSCT, and the combination of
      CsA, MTX , mycophenolate mofetil (MMF), and antithymocyte globulin (ATG) in
      unrelated donor all-HSCT to prevent graft versus host disease (GVHD). Kaplan
      Meier survival analysis model was used to estimate the overall survival and the
      disease-free survival (DFS) at 5 years after transplantation. RESULTS: In 8
      patients with autologous transplantation, 7 obtained partial or complete
      cytogenetic remission (CR) within 3 months after transplantation and one died of
      transplantation-related complication. In 49 patients with allo-HSCT
      transplantation, all patients obtained CR except for two patients, one of whom
      failed to obtain CR and the other died of hepatic veno-occlusive disease. The
      incidence of infection and veno-occlusive disease during transplantation was
      33.3% and 7.0%, respectively. The incidence of hemorrhagic cystitis and
      cytomegalovirus interstitial pneumonia after transplantation was 22.8% and 8.8%,
      respectively. Veno-occlusive disease, hemorrhagic cystitis or cytomegalovirus
      interstitial pneumonia did not occur in patients with autologous transplantation.
      The incidence of acute GVHD was 41.0% and 48.6%, and that of chronic GVHD 40.0%
      and 42.9% in patients with related and unrelated transplantation, respectively.
      The rate of relapse was 57.1% and 12.8%, with DFS at 5 years of 25.0% and 61.7%,
      respectively, in patients with autologous and related donor transplantation. The
      DFS at 5 years was 70.7% and 34.1%, respectively, in patients with
      chronic/accelerated phases and blast crisis be fore trans plantation. CONCLUSION:
      allo-HSCT can produce a higher clinical cure rate in CML patients in chronic
      phase CsA+MTX+MMF+ ATG protocol is more effective for prevention and alleviation
      of acute GVHD in patients with unrelated donor transplantation. Autologous
      transplantation with bone marrow purging helps prolong the patients' survival and
      even obtain clinical cure of CML.

PMID- 15567764
TI  - [Optimization of the conditions for protein chip preparation].
AB  - OBJECTIVE: To define the optimal conditions for preparing protein chips on
      aldehyde-coated slides. METHODS: The proteins were diluted in PBS containing 40%
      glycerol and spotted on aldehyde-coated slides. After the spots were dried for 1
      hour at room temperature, the slides were stored at 4 degrees Celsius;. Following
      block and rinse, the slides were used for immunoassay and the results detected
      with a scanner. Several key factors that might influence the results were tested,
      including the number of spots, concentration of protein in the spotting solution,
      time of immobilization and the blocking reagent. RESULTS: Pre-spotting of 10 to
      15 spots achieved good homogeneity of the subsequent spots on aldehyde-coated
      slides. The protein immobilized at 4 degrees Celsius; for 24 to 48 h showed
      higher fluorescence intensity and clearer images, and the slides blocked with 3%
      BSA produced the lowest background signal. The concentration of protein in the
      spotting solution significantly affected the fluorescence intensity. CONCLUSION:
      To ensure good results in preparing protein chips on aldehyde slides, pre
      spotting of 10-15 spots can be necessary followed by immobilization at 4 degrees
      Celsius; for 24-48 h and 3% BSA blocking.

PMID- 15567765
TI  - [Establishment and evaluation of the method for removing albumin and IgG in serum
      proteomics].
AB  - OBJECTIVE: To establish and evaluate the method for removing albumin and IgG in
      serum proteomics. METHODS: Elimination of serum albumin and IgG was achieved by
      filtering with Micro Bio-Spin column and the efficiency of purification evaluated
      by two-dimensional polyacrylamide gel electrophoresis (2-DE). RESULTS: The method
      for removing serum albumin and IgG was established, which enabled visualization
      of low-abundance proteins better in 2-DE map. CONCLUSION: The established method
      for purifying serum proteins can be effectively applied in serum proteomic study
      of diseases.

PMID- 15567766
TI  - [Oligonucleotide microarray preparation using enhanced poly-L-lysine glass
      slides].
AB  - OBJECTIVE: To modify conventional poly-L-lysine coating for oligonucleotide
      microarray preparation so as to enhance the sensitivity of the microarray.
      METHOD: The proposed chemical approaches included silanizing the slides with 3
      glycid-oxypropyltrimethoxysilane (GOPS) after cleaning, followed by slide coating
      with polymers (poly-L-lysine) that was covalently bound to the modified glass.
      Subsequent attachment of the oligonucleotide to the modified slide surface was
      achieved after 1,4-phenylene diisothiocyanate (PDITC) activation of the surface.
      Various experiments were carried out, such as the immobilization efficiency and
      hybridization assays to test the modified slides, which were then used
      tentatively in the preparation of microarrays for SARS coronavirus detection.
      RESULTS: The improved surface had high immobilization efficiency, good uniformity
      and satisfactory hybridization efficiency, better than those slides with
      conventional poly-L-lysine coating. In addition, such modified slides rendered
      the microarrays more resistant to consecutive probing/stripping cycles.
      CONCLUSION: The modified slide surface is satisfactory to immobilize unmodified
      oligonucleotide by covalent binding, which enhances not only the sensitivity of
      the prepared oligonucleotide microarray but also the binding of the
      oligonucleotide to the slide surface.

PMID- 15567767
TI  - [Experimental study of a biological dural graft in rabbits].
AB  - OBJECTIVE: To evaluate the safety and efficacy of a dural graft prepared using
      porcine membrane in duraplasty. METHODS: Eighteen New Zealand rabbits were
      randomly divided into groups A (n=4), B (n=4), C (n=5), and D (n=5) sacrificed 3,
      14, 30 and 90 d after duraplasty, respectively. Each animal underwent bilateral
      parietal craniectomy behind the coronal suture and beside the midline to expose
      the dura, which was cut on the right side and substituted with the dural graft.
      The exposed dura on the left was kept intact as control. The rabbits were
      observed for WBC counts before the operation and before sacrifice by transcardiac
      formalin perfusion, respectively. The meninges and brain tissues were
      histologically examined after sacrifice. RESULTS: The WBC count varied little
      after the operation (P>0.05). Microscopic examination demonstrated tissue repair
      on both the implantation side and control side, without graft adhesion to the
      cortical surface. In group A, a large number of leukocytes were seen gathering on
      the lateral dura, suggesting acute tissue repair. In group B, endothelial cells
      covering the inner surface of the graft could be seen. Fibroblasts and fibrocytes
      were seen in the grafts between collagen fibers in group C, and in group D,
      fibroblasts and fibrocytes increased between the collagen fibers and the suture
      healed. CONCLUSION: The dura graft is safe and applicable for dural defect
      repair.

PMID- 15567768
TI  - [Expressions of early growth response 1 and tissue factor in caerulein-induced
      acute pancreatitis tissues in rats].
AB  - OBJECTIVE: To observe the expressions of early growth response 1 (Egr-1) and
      tissue factor (TF) in rat tissues of acute pancreatitis induced by caerulein and
      to explore their significance. METHODS: Pancreatitis was induced in rats by high
      dose intraabdominal caerulein injection. The changes of Egr-1 mRNA and protein in
      pancreas were measured by quantitative PCR and Western blotting, and the
      localization of Egr-1 protein in acinar cells was visualized by
      immunohistochemistry. TF mRNA levels were also measured by quantitative PCR. High
      dose bombesin-stimulated rats served as the negative control. RESULTS: Egr-1 mRNA
      was rapidly increased in the pancreas of rats stimulated by high-dose cearulein,
      and reached the peak level 30 min after the stimulation, whereas band for peak
      Egr-1 protein level was visualized by Western blotting till 2 h after
      stimulation. Immunohistochemistry showed that almost every acinar cell in the
      pancreas was Egr-1-positive, especially in the nucleus. In line with Egr-1
      activation, TF mRNA was detected 1 h after the stimulation and increased steadily
      within the initial 4 h. Only a small quantity of Egr-1 mRNA expression was
      observed in bombesin-stimulated rats, in which no Egr-1 protein or TF mRNA were
      detected. CONCLUSION: Egr-1 mRNA and protein were up-regulated in the early stage
      of pancreatitis. Egr-1, as a pro-inflammatory transcriptional factor, probably
      plays an important role in the initiation of acute pancreatitis, and its action
      might be partially mediated through the up-regulation of TF expression.

PMID- 15567769
TI  - [Biological effect of serum of kidney-tonifying traditional Chinese drug-fed rats
      on cultured osteoblasts].
AB  - OBJECTIVE: To investigate the biological effects of the serum of rats fed with
      kidney-tonifying traditional Chinese drugs on cultured osteoblasts in vitro.
      METHODS: The culture media containing the serum from rats fed with the drugs at
      different doses (high, mediate and low doses) were used to treat the second
      passage of the osteoblasts from the skull of newborn SD rats, and the cell
      proliferation, differentiation and mineralization were observed. RESULTS: The
      serum stimulated the cell proliferation, enhanced alkaline phosphatase activity
      and increased the number of mineralized nodules in the cultured osteoblasts.
      CONCLUSION: Kidney-tonifying traditional Chinese drugs can stimulate the
      proliferation, differentiation and maturation of cultured osteoblasts in vitro.

PMID- 15567770
TI  - [Effect of clozapine and risperidone on serum cytokine levels in patients with
      first-episode paranoid schizophrenia].
AB  - OBJECTIVE: To study the effects of clozapine and risperidone on serum cytokine
      levels in patients with first-episode paranoid schizophrenia, and explore the
      role of the cytokines in the psychopathological basis of the illness. METHOD:
      Fifty-eight patients with first-episode paranoid schizophrenia were treated with
      either clozapine or risperidone, and before and at the end of the 4th, 8th weeks
      and 6th months after the medication respectively, the serum levels of interleukin
      (IL)-6, 2, 18,and tumor necrosis factor (TNF)alpha were measured with enzyme
      linked immunosorbent assay (ELISA). The Positive and Negative Syndrome Scale
      (PANSS) was used to evaluate the psychotic symptoms. RESULT: In patients treated
      with risperidone, the levels of serum IL-6 and IL-2 after 4 weeks, TNFalpha after
      8 weeks, and IL-18 after 6 months were all significantly lowered in comparison
      with the pretreatment levels (P<0.01 or 0.05). In clozapine group, the levels of
      IL-2 after 4 weeks and IL-6 and IL-18 after 6 months were lowered significantly
      (P<0.01 or 0.05). Before the medication, serum IL-6 level was positively
      correlated with Positive Syndrome scores (r=0.386, P<0.01), IL-2 with the total
      score and Positive Syndrome scores (r=0.338, 0.305; P<0.01, 0.05), and TNFalpha
      with the total score (r=0.283, P<0.05). The changes of IL-2 and IL-6 after 8
      weeks was positively correlated with the change of Positive Syndrome scores
      (r=0.268, 0.375; P<0.05, 0.01). Six months after the medication, the change in IL
      6 and TNFalpha levels was positively correlated with the change of total score
      (r=0.365, 0.362; P<0.05). Before treatment, IL-6 was positively correlated with
      IL-2 levels (r=0.356, P<0.01), and TNFalpha with IL-18 levels (r=0.291, P<0.05).
      TNFalpha was positively correlated with IL-6 levels (r=0.332, P<0.01) 8 weeks
      after the medication. The changes in IL-6 was positively correlated with the
      those in IL-2 levels 6 months after the medication (r=0.391, P< 0.05).
      CONCLUSION: Clozapine and risperidone have similar immunosuppression actions and
      may affect serum IL-6 levels in patients with paranoid schizophrenia, in the
      psychopathology of which the cytokines play their roles of various importance.

PMID- 15567771
TI  - [Effects of topical emu oil on wound healing in scalded rats].
AB  - OBJECTIVE: To observe the effect of topical emu oil on wound healing in scalded
      rats. METHODS: Thirty Wistar rats with second degree scald were randomized into
      emu oil group, povidone iodine group and liquid paraffin group. The times of
      twisting of the rat body, water content and effusion of the scald wound and the
      percentage of wound healing were observed. RESULTS: Compared with povidone iodine
      and liquid paraffin, emu oil reduced the times of body twisting of the scalded
      rats, the water content and effusion of the scald wound, and increased the
      percentage of wound healing. CONCLUSION: Emu oil can alleviate inflammation in
      the scald wound and promote wound healing in rats.

PMID- 15567772
TI  - [Detection of the Salmonella invasion gene invA using molecular beacon probe].
AB  - OBJECTIVE: To detect Salmonella invasion gene invA. METHODS: The invA gene of
      Salmonella was amplified with PCR reaction system containing the molecular beacon
      probe labeled with 6-carboxy fluorescein (6-FAM) at its 5' end and with (4
      dimethylaminophenylazo)benzoic acid (DABCYL) at its 3' end, and the fluorescence
      signal was read at the end of PCR. RESULTS: The fluorescence values of
      S.enteritidis, S. paratyphi A, S. paratyphi B, S.typhi antigen H, S.typhi, and
      enteroinvasive E.coli were 161.6, 104.5, 85.9, 83.1, 94.8 and 46.1 respectively.
      The results of PCR of Salmonella was consistent with that of agarose gel
      electrophoresis. CONCLUSION: PCR with fluorogenic molecular beacon probe is
      rapid, specific, sensitive, and convenient for detecting Salmonella with invA
      gene.

PMID- 15567773
TI  - [Effects of ureteral stents on rabbit upper urinary tract urodynamics].
AB  - OBJECTIVE: To explore the effects of ureteral stent placement on ureteral
      peristalsis and the time course of renal pelvic pressure changes. METHOD: Forty
      rabbits were randomized equally into 8 groups, including a control group without
      placement of ureteral stents. The other 7 groups received ureteral stent
      placement, which were retained for 0, 1, 2, 3, 4, 7, and 12 weeks respectively.
      When the rabbits were bred for the specified time periods, ureteral peristalsis
      was observed and renal pelvic pressure measured. RESULT: The renal pelvic
      pressure was initially increased after the stent placement, but then followed by
      gradual decreases. Ureteral peristalsis was not observed after the stent
      placement. CONCLUSION: Ureteral stent is a factor for causing obstruction in
      normal ureter.

PMID- 15567774
TI  - [Rapid serum-free culture of dendritic cells from human peripheral blood
      monocytes and their intracellular signal transduction].
AB  - OBJECTIVE: To explore the methods for rapid in vitro culture of the dendritic
      cells (DCs) from human peripheral blood monocytes (PBMCs) under serum-free
      conditions and ascertain whether intracellular signal transduction pathway
      differs between calcium ionophore (CI) and tumor necrosis factor (TNF)- alpha
      during their induction of dendritic cell differentiation. METHODS: PBMCs isolated
      from healthy donors were plated in serum-free medium supplemented with 50 ng/ml
      rhGM-CSF. Cells cultured overnight were induced to differentiate with 100 ng/ml
      A23187 or 50 ng/ml TNF-alpha, given before or 30 min after pre-treatment with 0.5
      mug/ml cyclosporine A (CsA). After culture for 40 h, the cell morphology was
      observed under phase-contrast microscope, and the surface markers on treated
      PBMCs were analyzed by flow cytometry. MTT colorimetry was employed to assess the
      proliferation of the allogeneic T cells. RESULTS: PBMCs of healthy donors treated
      with 50 ng/ml rhGM-CSF in combination with 100 ng/ml CI or 50 ng/ml TNF-alpha for
      40 h exhibited typical morphology of DCs with rapidly decreased CD14 expression
      and increased expressions of CD83 and co-stimulatory molecules (CD80 and CD86),
      showing also enhanced ability of stimulating allogeneic T cell proliferation.
      Calcineurin antagonist CsA inhibited the differentiation induced by CI, but not
      that induced by TNF-alpha. CONCLUSIONS: Under serum-free conditions, both CI and
      TNF-alpha are capable of inducing rapid DC differentiation from human PBMCs, but
      the intracellular signal transduction of CI-induced differentiation is different
      from that induced by TNF-alpha.

PMID- 15567775
TI  - [Comparative studies of serological typing and HLA-A, B antigen genotyping with
      PCR using sequence-specific primers].
AB  - OBJECTIVE: To evaluate the accuracy of PCR with sequence-specific primers (PCR
      SSP) for HLA-I genotyping and analyze the causes of the errors occurring in the
      genotyping. METHODS: DNA samples and were obtained from 34 clinical patients, and
      serological typing with monoclonal antibody (mAb) and HLA-A and, B antigen
      genotyping with PCR-SSP were performed. RESULTS: HLA-A and, B alleles were
      successfully typed in 34 clinical samples by mAb and PCR-SSP. No false positive
      or false negative results were found, and the erroneous and missed diagnosis
      rates were obviously higher in serological detection, being 23.5% for HLA-A and
      26.5% for HLA-B. Error or confusion was more likely to occur in the antigens of
      A2 and A68, A32 and A33, B5, B60 and B61. CONCLUSIONS: DNA typing for HLA-I class
      (A, B antigens) by PCR-SSP has high resolution, high specificity, and good
      reproducibility, which is more suitable for clinical application than serological
      typing. PCR-SSP may accurately detect the alleles that are easily missed or
      mistaken in serological typing.

PMID- 15567776
TI  - [Postoperative Th1 and Th2 type cytokine changes in patients with esophageal
      squamous cell carcinoma and their clinical significance].
AB  - OBJECTIVE: To study the expressions of Th1 and Th2 type cytokines in patients
      with esophageal squamous cell carcinoma and the influence of operation on such
      expressions. METHOD: Enzyme-linked immunosorbent assay (ELISA) was used to detect
      Th1 (IL-2 and INF-gamma) and Th2 type cytokines (IL-4, IL-6 and IL-10) in
      cultured peripheral blood mononuclear cells (PBMCs, for 48 h) from 30 healthy
      controls and 46 esophageal squamous cell carcinoma patients (collected before and
      8 and 30 d after operation, respectively). RESULTS: Compared with the control
      group, the expressions of Th1 type cytokines, IL-2 and INF-gamma, were
      significantly depressed in the PBMCs of the cancer patients (P<0.05), while
      expression of Th2 type cytokines, IL-6 was significantly enhanced (P<0.05), and
      IL-4 and IL-10 showed only slight enhancement. Such changes in the expressions of
      the cytokines showed a correlation with TNM (tumor-node-metastasis)stage of the
      tumors. After operation, the expressions of Th1 type cytokines increased and Th2
      type cytokines decreased. CONCLUSIONS: Th1 cells are suppressed in patients with
      esophageal squamous cell carcinoma, while the function of Th2 cells is enhanced.
      Operation may reverse such changes, and dynamic detection of Th1 and Th2 type
      cytokines may indicate the prognosis, therapeutic effect and risks of relapse and
      metastasis.

PMID- 15567777
TI  - [Changes of neuronal nitric oxide synthase-immunopositive neurons in the central
      amygdaloid nucleus of spontaneously hypertensive rats].
AB  - OBJECTIVE: To observe the changes of neuronal nitric oxide synthase (nNOS)
      immunopositive neurons in the central amygdaloid nucleus of spontaneously
      hypertensive rats (SHRs). METHODS: Thirty SHRs and 30 Wistar-Koyto rats (WKYs)
      were sacrificed at the ages of 90, 180, and 360 days respectively to observe the
      changes of nNOS-immunopositive neurons with ABC immunocytochemical assay.
      RESULTS: No significant changes were observed in the blood pressure of WKY rats
      at the specified time points, when SHRs maintained significantly higher blood
      pressures from 20.8+/-1.1 and 26.3+/-1.0 kPa (P<0.05), gradually increasing
      during the development of hypertension. The nNOS-immunopositive neurons in the
      central amygdaloid nucleus were of moderate sizes with long intersected nerve
      fibers. No significant changes were found in WKY rats. The number of the positive
      neurons decreased with age in SHRs, especially obvious at 360 days (P<0.05),
      which was significantly different from that in the WKYs (P<0.05). CONCLUSION: The
      reduction of nNOS-immunopositive neurons in the central amygdaloid nucleus of
      SHRs might accelerate the development of hypertension by modulating the
      cardiovascular function and sensory transmission.

PMID- 15567778
TI  - [Effects of cyclosporine A on NIT-1 beta cell proliferation and pol alpha1 gene
      expression in vitro].
AB  - OBJECTIVE: To investigate the effects of cyclosporine A on the proliferation and
      pol alpha1 mRNA expression of cultured NIT-1 beta cells. METHODS: After exposure
      to cyclosporine A at various concentrations (0.05 to 10 micromol/L) for 48 h and
      72 h, NIT-1 cell proliferation was analyzed by MTT assay and the gene expression
      determined by reverse transcriptional PCR (RT-PCR). RESULTS: Forty-eight-hour and
      72-hour cyclosporine A exposure inhibited the cell proliferation in a
      concentration- dependent manner, and at the concentration of 10 micromol/L,
      cyclosporine A also decreased pol alpha1 mRNA expression after a 48-hour
      exposure. CONCLUSION: Cyclosporine A can effectively inhibit the proliferation of
      NIT-1 cells possibly through down-regulating the expression of pol alpha1 mRNA.

PMID- 15567779
TI  - [Extraintestinal dissemination of rotavirus in immunodeficient mice].
AB  - OBJECTIVE: To investigate the extraintestinal dissemination of rotavirus (RV) in
      immunodeficient mice. METHODS: Immunodeficiency mouse model was established by
      injection of cyclophosphamide into the abdominal cavities of normal mice, then to
      which RV was administered either orally or intra-abdominally. The pathological
      changes in the organs were observed by light microscopy and RV was detected by in
      situ hybridization and PCR. RESULTS: Small intestinal villi, gastric lamina
      propria and cardiac myocytes exhibited pathological changes in the mice with oral
      RV administration. Besides these changes, the mice with intra-abdominal RV
      injection showed changes in the liver and kidneys. The intestinal villi of the
      mice with oral RV were RV positive by in situ hybridization. Positive results of
      RV in in situ PCR detection were found in the intestinal villi, intestinal gland
      cells, epithelial cells of the proximal convoluted tubules and collecting tubes
      in the kidney of the mice taken RV orally, and in the intestinal villi, kidneys,
      liver, heart and pancrease of mice with intra-abdominal RV injection. CONCLUSION:
      Immunodeficiency may be the important factor for inducing and aggravating the
      infection and extraintestinal dissemination of RV.

PMID- 15567780
TI  - [Prevalence of hemorrhagic fever with renal syndrome virus in domestic pigs: an
      epidemiological investigation in Shandong province].
AB  - OBJECTIVE: To investigate the epidemiological significance of hemorrhagic fever
      with renal syndrome virus (HFRSV) infection in domestic pigs in Shandong
      province, and study the role of domestic pigs in the prevalence of HFRS. METHODS:
      Epidemiological investigation was performed in 4 cities of Shandong province.
      Reversed passive hemagglutination assay (RPHA), reversed passive hemagglutination
      inhibition (RPHI), HPR-SPA, immunofluorescent antibody (IFA), and reverse
      transcriptional PCR (RT-PCR) were used to detect antigen and antibody of HFRSV.
      RESULTS: HFRSV antigen and antibody were detected in the heart, liver, lung,
      spleen, kidney, blood, urine, and stool of domestic pigs as well as in the sewage
      of the pigpen facilities. The positivity rate of HFRSV antigen ranged from 3.33%
      to 5.00% in the organ of pigs, and HFRSV positivity rate in the blood, urine,
      stool, and sewage was 3.67%, 7.04%, 2.51%, and 5.56%, respectively, with a total
      serum antibody positivity rate of 1.96%. The virus was isolated from the HFRSV
      antigen-positive samples, and could infect many organs after artificial infection
      of the pigs. HFRSV antigen can be detected in suckling rat brain and
      histopathological examination suggested transient pathological changes in such
      organs as the liver, lung and kidney. HFRSV may proliferate in pigs and was
      discharged through multiple routes. CONCLUSION: Domestic pigs can be the host of
      HFRSV for the viral transmission.

PMID- 15567781
TI  - [Epidemiological survey of HBsAg carriers in the Uighur and Han populations in
      the Khotan Area of Xinjiang autonomous region].
AB  - OBJECTIVE: To survey nonsymptomatic HBsAg carriers in the Uighur and Han
      populations in Khotan Area of Xinjiang Autonomous region. METHOD: HBsAg was
      detected using colloidal gold-labeled double antibody sandwich method. RESULTS:
      These investigations included 2 597 subjects consisting of 2 022 Uighur and 575
      Han subjects. The total HBsAg carrier rate in the Uighur population was 1.48%
      (30/2 022), specifically 1.078% in male and 1.59% in female subjects. No
      significant differences were observed in the age between male and female HBsAg
      carriers, who had an average age of 35 years. In the Han population, the total
      HBsAg carrier rate was 6.09% (30/575), and was 5.6% in male and 4.4% in female
      subjects. The average age of the male carriers was 36.3 years and 27.6 years in
      the female carriers, which showed significant difference in respect to HBsAg
      carrier rate. The HBsAg carrier rate showed significant difference between Uighur
      and Han populations in Khotan Area (P<0.01). CONCLUSIONS: The HBsAg carrier rate
      in Uighur population in Khotan Area is consistent with that in areas with low HBV
      infection, whereas the Han population exhibit features similar to those in areas
      with moderately HBV prevalence in the inland regions. The low HBsAg carrier rate
      in Uighurs might be attributed to the their customs in diet, eating habit, local
      living environment and the difference in HLA gene distribution. The authors
      suppose that such antigens as HLA-Bw41 might be protective against HBV infection.

PMID- 15567782
TI  - [Radiation-induced rat cerebral neuron apoptosis].
AB  - OBJECTIVE: To explore the correlation between X-ray-induced rat cerebral neuron
      apoptosis and radiation doses. METHODS: In a controlled experiment, the rats in
      the experimental group received X-ray radiation at different doses (2, 4, 6 and 8
      Gy), and the apoptotic cerebral neurons were counted after in situ end-labeling
      and immunohistochemical staining. RESULTS: X-ray radiation induced apoptosis of
      rat cerebral neurons, and the apoptotic rate varied with the radiation doses.
      Significant difference in the apoptotic rate was noted before and after radiation
      (P<0.0001), and between different radiation dose groups (P<0.005). The apoptotic
      rate differed significantly at different time points after the radiation.
      CONCLUSION: Low or medium doses of X-ray is able to induce rat cerebral neuron
      apoptosis depending on the radiation doses and following a definable time course.

PMID- 15567783
TI  - [Effects of iodine-containing food on 99mTc and 131I uptake in patients with
      Graves' disease].
AB  - OBJECTIVE: To investigate the changes in 99mTc and 131I uptake in patients with
      Grave's disease after intake of iodine-containing food. METGIDSl The 3-hour and
      24-hour radioactive iodine uptake (RAIU) and 99mTc uptake ratio (TI) were
      measured and the thyroid weight (TW) was estimated in 20 patients with Graves'
      disease both before and after restraint of iodine-containing diet. RESULTS:
      Significant difference was found in RAIU and TI in patients after restraint of
      iodine-rich diet (Z=3.920, P=0.000 for 3-hour RAIU and Z=3.920, P=0.000 for 24
      hour RAIU; Z=2.199, P=0.028 for TI and Z=3.920, P=0.000 for TW estimated from
      99mTc images). The tendency in such changes was significantly different (Z=4.066,
      P=0.000 for RAIU and TI; Z=4.243, P=0.000 for RAIU and TW). After restraint of
      iodine-rich food, RAIU of 3-hour and 24-hour increased in all the patients, and
      TI decreased in 16, remained the same level in 2 and increased in 2 patients; TW
      decreased in 18 and increased in 2 patients. CONCLUSION: Iodine-containing food
      has different effects on thyroid 131I and 99mTc uptakes, which decreases 131I
      uptake in all the patients and increases 99mTc in 90% of them.

PMID- 15567784
TI  - [Impact of allograft weight and the recipient's body weight on long-term
      allograft function].
AB  - OBJECTIVE: To investigate the relationship of the renal allograft weight and the
      recipient's body weight with allograft function after transplantation. METHODS:
      The correlation of the renal allograft weight, the recipient's body weight, the
      ratio of the allograft weight to the recipient body weight and the mean serum
      creatinine (sCr) 3 years after transplantation were measured in 108 kidney
      recipients. RESULTS: The allograft weight was inversely correlated with the mean
      sCr 3 years after transplantation (P<0.01). CONCLUSION: The renal allograft
      weight, recipient's body weight and the ratio of allograft weight to recipient's
      body weight are important indicators of the long-term allograft function after
      transplantation, and recipients with greater body weight should receive
      allografts of higher weight.

PMID- 15567785
TI  - [Effect of 3-dimensional conformal hypofractionated high-dose radiotherapy
      combined with chemotherapy for non-small-cell lung cancer: a clinical
      observation].
AB  - OBJECTIVE: To evaluate the clinical therapeutic effect of three-dimensional
      conformal hypofractionated high-dose radiotherapy combined with chemotherapy for
      non-small-cell lung cancer (NSCLC). METHODS: The combined treatment was carried
      out in 63 cases of NSCLC and the short-term effects, the patients' survival rate
      and complications were observed. RESULTS: Local control of tumor growth was
      achieved in 79.1% of the patients and the survival rates of 1, 3, and 5 years
      were 65.2%, 23.2%, and 10.4%, respectively. The median actual survival of the
      patients was 14 months. Late radiation pneumonitis (grade 3 or 4) and
      oesophagitis occurred in 9.5% and 4.8% of the patients, respectively.
      CONCLUSIONS: Three-dimensional conformal hypofractionated high-dose radiotherapy
      combined with chemotherapy can be an effective and practical approach to treat
      NSCLC, but local recurrence remains the major factor of treatment failure.

PMID- 15567786
TI  - [Investigation of cross-infection of Pseudomonas aeruginosa in an intensive care
      unit].
AB  - OBJECTIVE: To investigate the factors responsible for Pseudomonas aeruginosa
      nosocomial cross-infection in the intensive care unit (ICU) and provide effective
      measure for the prevention and management. METHODS: The homology of 7 Pseudomonas
      aeruginosa strains isolated from the patients in the ICU and the environment was
      examined by biological, serological, drug-resistance and plasmid analysis.
      RESULTS: The results of serological and plasmid analyses had good consistency,
      which demonstrated that the 7 Pseudomonas aeruginosa strains originated from
      solution in the oxygen humidifier, with uniform serological and plasmid type, and
      belonged to the same clone with cross-infection by contact between the patients
      or nursing staff and the objects in the ICU. CONCLUSION: Serological and plasmid
      analyses are more practical for identifying the sources of Pseudomonas aeruginosa
      cross-infection, which can be prevented by strict disinfection of the instrument
      and supervision of the nursing staff in the ICU.

PMID- 15567787
TI  - [Expression of macrophage migration inhibition factor in pancreatic carcinoma
      tissue].
AB  - OBJECTIVE: To observe the expression of macrophage migration inhibitory factor
      (MIF) in pancreatic carcinoma tissue and analyze the relationship between MIF
      expression and clinical manifestations. METHODS: MIF expression in pancreatic
      carcinoma and normal pancreatic tissue were detected with immunohistochemical
      method. RESULT: The positivity rates of MIF in pancreatic carcinoma and normal
      pancreatic tissue were 69.4% (25/36) and 0 (0/10) respectively. MIF expression
      was found to relate to the degree of cell differentiation of pancreatic
      carcinoma, but not to the clinical stages or the status of lymph node metastasis.
      CONCLUSION: MIF might be related to the pathogenesis of pancreatic carcinoma.

PMID- 15567788
TI  - [Intravenous propofol combined with fentanyl for anesthesia during ultrasound
      guided transvaginal oocyte retrieval].
AB  - OBJECTIVE: To compare the clinical efficacy and safety of anesthesia with
      intravenous propofol combined with fentanyl for ultrasound-guided transvaginal
      oocyte retrieval. METHODS: Totally 100 unpremedicated infertile women (ASA I-II)
      scheduled for oocyte retrieval with ultrasound guidance were randomly divided
      into two groups to receive anesthesia with either intravenous propofol (group A,
      n=50) or the combination of propofol and fentanyl (group B, n=50). The time when
      consciousness loss and recovery occurred, dosage of propofol for anesthesia
      maintenance, mean arterial blood pressure (MAP), heart rate (HR) and oxygen
      saturation (SpO2) were recorded. RESULTS: There was no significant difference in
      the time of consciousness loss between groups A and B (58.8+/-3.8 s vs 57.7+/-5.2
      s, P=0.283), but consciousness recovery occurred earlier in group B (6.0+/-0.6
      min vs 5.7+/-0.4 min, P<0.01). The maintenance dosage of propofol in group B
      (0.20+/-0.03 mg/kg) was significantly lower than that in group A (0.52+/-0.05
      mg/kg, P<0.01). At 2 min after anesthesia induction, the MAP decreased from
      11.1+/-0.8 kPa to 8.0+/-0.6 kPa in group A (P<0.05), and from (10.9+/-0.9) kPa to
      (8.3+/-0.7) kPa in group B(P<0.05), and returned to normal within 2-3 min in both
      groups. The incidence of low SpO2 (<90%) was lower in group A than in group B
      ((52% vs 88%, P<0.001). CONCLUSION: Anesthesia with propofol combined with
      fentanyl may reduce the maintenance dosage of propofol, shorten the time of
      consciousness recovery during oocyte retrieval with ultrasound guidance, and can
      be helpful for the patients' early recovery and discharge from hospital.

PMID- 15567789
TI  - [Clinical application of composite skin graft consisting of acellular allogenic
      dermis and autologous skin].
AB  - OBJECTIVE: To study the procedures of applying composite skin graft consisting of
      acellular allogenic dermis and autologous skin in the treatment of full-thickness
      burns and scar formation. METHODS: Fifteen burn wounds in 8 patients were treated
      with the composite skin graft using one-stage grafting. RESULTS: Complete wound
      healing was achieved in 13 wounds. The external appearance, texture and
      flexibility of the grafted skin were satisfactory in most cases and no obvious
      scar formation was observed. CONCLUSION: One-stage grafting of the composite skin
      graft yields a high success rate for most burn wounds with good basal layer
      condition.

PMID- 15567790
TI  - [Diagnosis and short-term therapeutic effect of AIDS complicated by
      tuberculosis].
AB  - OBJECTIVE: To investigate the shore-term therapeutic effects of AIDS complicated
      by tuberculosis. METHODS: Ninety-eight AIDS patients with tuberculosis living in
      a village in Henan province were observed. RESULTS: Among the 98 patients, fever,
      cough, night sweating, weight loss, and superficial lymph node swelling were the
      common symptoms. Highly active anti-retroviral therapy (HAART) combined with a 6
      month anti-tuberculosis treatment protocol with streptomycin, isoniazid,
      rifampin, and pyrazinamide (2SHRZ/4HRZ) resulted in improvement of the patients'
      clinical symptoms and signs as well as the immune functions. CONCLUSION: AIDS
      complicated by tuberculosis should receive due medical attention and sputum smear
      examination for anti-acid bacillus combined with X-ray examination possesses good
      diagnostic value for tuberculosis in these patients, for whom short-term anti
      tuberculosis treatment may have beneficial effects.

PMID- 15567791
TI  - [Changes in myocardial enzyme spectrum and electrocardiogram after Salmonella
      food poisoning].
AB  - OBJECTIVE: To study the changes in myocardial enzyme spectrum in relation to
      electrocardiogram (ECG) in Salmonella food poisoning. METHODS: The myocardial
      enzyme spectrum and ECG of 56 patients with Salmonella food poisoning were
      examined, with 34 normal subjects serving as the control group. RESULTS: In the
      food poisoning group, the myocardial enzyme activities was increased in 36 cases
      (64.29%) within 2 days after the poisoning and the ECG of 33 cases (58.93%)
      showed abnormal changes within 1-4 days. The levels of creatine phosphoskinase
      (CPK) and alpha-hydroxybutyrate acid dehydrogenase (alpha-HBDH) in poisoning
      group were obviously higher than those in the control group (P<0.01). CONCLUSION:
      Routine examination of myocardial enzyme spectrum and ECG helps define early
      changes in patients with Salmonella food poisoning for clinical treatment
      decision.

PMID- 15567792
TI  - [Effect of argon laser photocoagulation on diabetic retinopathy].
AB  - OBJECTIVE: To observe the clinical effect of argon laser photocoagulation on
      diabetic retinopathy (DR) in different stages. METHODS: A total of 263 eyes in
      170 patients with DR in different stages were photocoagulated using argon laser
      machine 2000. Thirty eyes in non-proliferative stage received focal
      photocoagulation, 156 pre-proliferative eyes received subtotal panretina
      photocoagulation, and 77 proliferative eyes were treated with panretinal
      photocoagulation. Additional focal or grid treatment was given for the eyes with
      localized or diffused macular edema. The visual acuity, eye fundus examination
      and retinal fluorescein angiography were carried out 3 months after the treatment
      and the results compared with the preoperative findings. RESULTS: Improvement of
      visual acuity by at least one row on the visual chart was achieved in 92 eyes
      (35%), 144 eyes (55%) exhibited no changes, and 27 eyes (10%) deteriorated.
      Microaneurysm, retinal edema, exudates and fluorescence leakage were reduced in
      89% of the eyes, with the rest eyes requiring additional treatment in the non
      proliferative and pre-proliferative stages. For the retina in proliferative
      stage, neovascularization on the disc resolved completely in 67% eyes, whereas
      partially in 33% eyes which needed additional photocoagulation. The eyes with
      partial and complete resolution of macular edema accounted for 91% of the total
      eyes. Postoperative pre-retinal hemorrhage and vitreous hemorrhage occurred at
      the rates of 8% and 1%, respectively. CONCLUSION: Argon laser therapy is
      effective for the eyes with DR in different stages, but produces better efficacy
      in non- and pre-proliferative stages than in proliferative stage. Follow-up and
      additional photocoagulation are necessary for the eyes in proliferative stage to
      ensure better outcome.

PMID- 15567793
TI  - [Correlation between age and average apparent diffusion coefficient in normal
      appearing cerebral white matter].
AB  - OBJECTIVE: To quantitatively study the effect of ages on the average apparent
      diffusion coefficient (ADCav) of normal-appearing white matter. METHODS: Fifty
      patients with normal-appearing white matter were divided into four age groups,
      namely 16-30 years, (n=13), 31-45 years (n=12), 46-60 years (n=14) and >60 years
      (n=11). All the subjects were examined with conventional and trace-weighted
      diffusion imaging in three orthogonal directions. The ADCav of the white matter
      was measured and compared between various age groups. RESULTS: In the white
      matter, the ADCav of all the patients was (0.71+/-0.08) x 10(-3) mm2/s; the ADCav
      of the white matter in the first to fourth age groups were (0.69+/-0.06) x 10(-3)
      mm2/s, (0.71+/-0.07) x 10(-3) mm2/s, (0.71+/-0.09) x 10(-3) mm2/s, and (0.73+/
      0.10) x 10(-3) mm2/s respectively. ADCav of patients between 16-30 years was
      significantly different from that of patients over 60 years of age (P=0.014).
      Patients older than 60 years had an ADCav of the white matter significantly
      higher than the value of (0.70+/-0.07) x 10(-3) mm2)/s in the total patients
      younger than 60 years (P=0.026). CONCLUSION: Water diffusibility shows a slight
      increase in human white matter with aging, possibly due to mild ultrastructural
      changes associated with aging.

PMID- 15567794
TI  - [Effects of Xiaochaihu Tang, a traditional Chinese medicinal preparation, on
      ectopic endometrium in rats].
AB  - OBJECTIVE: To investigate the effects of Xiaochaihu Tang (XCHT), a traditional
      Chinese medicinal preparation, on ectopic endometrium in rats. METHODS: In rat
      models of endometriosis, the effect of XCHT of ultrastructure of the ectopic
      endometrium was observed by transmission electron microscopy. RESULTS: After
      treatment with XCHT at moderate (500 g/L) or high dose (750 g/L), ectopic
      endometrial growth was significantly inhibited (P<0.01); small-dose XCHT (250
      g/L) was less effective (P<0.05). The volume of endometrium implant in the
      control group remained unchanged (P>0.05). The glandular cells in the endometrial
      implant after therapy with moderate- or high-dose XCHT showed characteristic
      features of apoptosis, presented by decreased cell size, karyopyknosis, cytoplasm
      and nuclear chromatin condensation, increased density and presence of apoptotic
      bodies. Some stromal cells displayed degenerative and necrotic changes.
      CONCLUSION: XCHT may inhibit the growth of ectopic endometrium by inducing cell
      death in the form of apoptosis and necrosis.

PMID- 15567795
TI  - [Predicting human tumor-specific promoter using transcription factor binding
      sites].
AB  - To predict human tumor-specific promoters using computer technology, three data
      sets of tumor-specific promoter sequences, transcription factor binding site
      sequences and non-tumor promoter sequences were collected, and the tumor-specific
      promoter sequences and non-tumor promoter sequences were analyzed for the
      comparative density of each unique transcription factor binding site. The density
      of each transcription factor binding site in the corresponding data set was used
      to derive the density ratio, from which the eigenvector was constructed to
      identify human tumor-specific promoters. This method proved to be highly accurate
      in predicting the tumor-specific promoters, with recognition rates of over 90% of
      the training sequences and over 80% of the testing sequences.

PMID- 15567796
TI  - [Effects of fentanyl on EC50 of ropivacaine for postoperative epidural analgesia
      after gynecological surgery].
AB  - OBJECTIVE: To determine the effect of fentanyl on 50% effective concentration
      (EC50) of ropivacaine for postoperative epidural analgesia following
      gynecological surgery. METHODS: Sixty-five patients (ASA class I to II) scheduled
      for elective gynecological surgery were randomly divided into two groups to
      receive 20 ml ropivacaine (group R, n=33) or ropivacaine combined fentanyl (group
      RF, n=32) for postoperative epidural analgesia. The concentration of ropivacaine
      was adjusted according to double-blinded up-down sequential allocation. The
      efficacy was assessed using visual analog scores (VAS) and EC50 calculated using
      method of Dixon. RESULTS: The EC50 of ropivacaine was 0.098% in group R and
      0.069% in group RF, showing significant difference (P<0.01). CONCLUSION: EC50 of
      ropivacaine for postoperative epidural analgesia determined by up-down sequential
      allocation is 0.098%, which can be decreased by the use of fentanyl.

PMID- 15567797
TI  - [Combination of Fu needling with electric acupuncture for tennis elbow].
AB  - OBJECTIVE: To observe the clinical effect of Fu needling combined with electric
      acupuncture in treating tennis elbow. METHOD: One hundred patients with tennis
      elbow were divided into 3 groups randomly to receive the treatment with Fu
      needling (n=30), treatment with electric acupuncture (n=30), and treatment with
      the combination of the above 2 methods (n=40). The effects were observed 3 weeks
      after the treatment. RESULTS: All three therapies had good effects, but the
      combined therapy showed the best effect on tennis elbow. CONCLUSION: Fu needling
      combined with electric acupuncture may produce a higher cur rate of tennis elbow
      than either of the therapy used alone.

PMID- 15567798
TI  - [Application of external ultrasound-assisted tumescent liposuction in upper
      legs].
AB  - OBJECTIVE: To find a safe, effective and simple method for liposuction in the
      upper legs. METHODS: After appropriate choices of the incision, range of suction,
      and the method for liposuction, 32 patients received external ultrasound-assisted
      tumescent liposuction in the upper legs with local anesthesia. RESULTS: All the
      patients recovered smoothly and quickly from the operation with satisfactory
      effects of weight reduction and shaping of the legs, and no obvious complications
      occurred in these cases. CONCLUSION: External ultrasound-assisted tumescent
      liposuction is safe, effective and simple for removing local fat deposit in the
      upper legs.

PMID- 15567799
TI  - [Cyst puncture aspiration in 40 cases of abdominal echinococcosis].
AB  - OBJECTIVE: To evaluate the efficacy of cyst puncture aspiration in treating
      abdominal echinococcosis. METHOD: A retrospective analysis was performed in 40
      cases of abdominal echinococcosis with formation of isolated single cyst in close
      adhesion with the abdominal wall, for which cyst puncture aspiration was carried
      out under ultrasound guidance. RESULTS: No death occurred in these patients and
      only 15 developed mild fever. The days for antibiotic use, jaundice resolution,
      bile secretion, time of extubation and hospital stay were 2.88+/-0.65, 3.50+/
      0.71, 4.25+/-0.96, 5.38+/-0.98 and 9.35+/-1.08 days, respectively. Ultrasound
      examination in the follow-up showed no relapse in these patients, with the time
      of the residue adhesive cyst closure and calcification of 4.50+/-1.13 and 13.90+/
      2.38 months, respectively. CONCLUSION: Cyst puncture aspiration under ultrasound
      guidance produces good therapeutic effects on abdominal echinococcosis with
      isolated single cyst closely adhering to the abdominal wall.

PMID- 15567800
TI  - [Intraoperative treatment of cyst contents in abdominal echinococcosis].
AB  - OBJECTIVE: To study the methods for intraoperative treatment of the cyst contents
      in patients with abdominal echinococcosis. METHOD: Sixty-nine cases of abdominal
      echinococcosis were reviewed for intraoperative disposal of the cyst contents
      using 5% formaldehyde (group A, 33 cases) or 25% NaCl solution (group B, 36
      cases), and the effects and incidence of complications were compared. RESULTS: No
      relapse occurred in 33 cases with 5% formaldehyde treatment of the cyst contents,
      but postoperative intestinal fistula took place in 8 cases. In 36 cases with 25%
      NaCl treatment of the cyst contents, relapse occurred in one case postoperatively
      but no complications were seen in other patients. CONCLUSION: Treatment of the
      cyst contents with 5% formaldehyde may lead to intestinal fistula, and 25% NaCl
      solution may give rise to the risk of recurrence, so that both methods need
      improvement.

PMID- 15567801
TI  - Circulating fetal DNA in maternal plasma is increased in pregnancies at high
      altitude and is further enhanced by preeclampsia.

PMID- 15567802
TI  - Small (< 2.0-cm) breast cancers: mammographic and US findings at US-guided
      cryoablation--initial experience.
AB  - PURPOSE: To determine the mammographic and ultrasonographic (US) findings at
      cryoablation of small solitary invasive breast cancers and compare them with
      presence of residual malignancy after treatment. MATERIALS AND METHODS:
      Institutional review board approval and informed patient consent were obtained.
      Nine patients with small solitary invasive breast cancers diagnosed at core
      biopsy were treated with US-guided cryoablation and a 2.7-mm cryoprobe. Mean
      cancer size was 12 mm (range, 8-18 mm); four were palpable. Tabletop argon gas
      based cryoablation system with a double-freeze-thaw protocol was used to treat
      cancers in outpatient setting. Tumor sites were excised at lumpectomy 2-3 weeks
      after cryoablation. Findings at mammography and US before, during, and after
      cryoablation were assessed to categorize densities and masses on mammograms and
      masses on US images with Breast Imaging Reporting and Data System (BI-RADS);
      maximum cancer size was measured. Imaging findings and clinical breast
      examination data were compared with histologic findings from lumpectomy specimens
      to determine presence of intraductal or invasive cancer. RESULTS: With US
      guidance, ice balls (maximal mean size, 4.4 cm) were formed around cancers.
      Before excision, eight patients underwent mammography; all had new focal
      densities (maximum size, 2.5-5.0 cm) at cancer sites. Six patients underwent
      preexcisional US; 100% of them had new hyperechogenicity in tissue surrounding
      cancer site. Seven (78%) of nine patients had no residual cancer; specimens
      contained fat necrosis. One patient had a small focus of invasive cancer; one had
      extensive multifocal ductal carcinoma in situ. Patients with BI-RADS category 1
      or 2 densities on mammograms or nonpalpable tumors had no residual malignancy. No
      residual invasive cancer occurred in tumors 17 mm or smaller or in cancers
      without spiculated margins at US. CONCLUSION: After cryoablation, there was
      increased echogenicity at US and increased density at mammography; these findings
      were observed in areas that approximated location and size of the ice ball. Tumor
      size, mammographic density, and US characteristics may be indicators of
      likelihood of complete cryoablation.

PMID- 15567803
TI  - Reinstitutionalisation in mental health care: comparison of data on service
      provision from six European countries.
AB  - OBJECTIVE: To establish whether reinstitutionalisation is occurring in mental
      health care and, if so, with what variations between western European countries.
      DESIGN: Comparison of data on changes in service provision. SETTING: Six European
      countries with different traditions of mental health care that have all
      experienced deinstitutionalisation since the 1970s--England, Germany, Italy, the
      Netherlands, Spain, and Sweden. OUTCOME MEASURES: Changes in the number of
      forensic hospital beds, involuntary hospital admissions, places in supported
      housing, general psychiatric hospital beds, and general prison population between
      1990-1 and 2002-3. RESULTS: Forensic beds and places in supported housing have
      increased in all countries, whereas changes in involuntary hospital admissions
      have been inconsistent. The number of psychiatric hospital beds has been reduced
      in five countries, but only in two countries does this reduction outweigh the
      number of additional places in forensic institutions and supported housing. The
      general prison population has substantially increased in all countries.
      CONCLUSIONS: Reinstitutionalisation is taking place in European countries with
      different traditions of health care, although with significant variation between
      the six countries studied. The precise reasons for the phenomenon remain unclear.
      General attitudes to risk containment in a society, as indicated by the size of
      the prison population, may be more important than changing morbidity and new
      methods of mental healthcare delivery.

PMID- 15567804
TI  - Parents' awareness of overweight in themselves and their children: cross
      sectional study within a cohort (EarlyBird 21).

PMID- 15567805
TI  - Young daughter cladodes affect CO2 uptake by mother cladodes of Opuntia ficus
      indica.
AB  - BACKGROUND AND AIMS: Drought damages cultivated C3, C4 and CAM plants in the semi
      arid lands of central Mexico. Drought damage to Opuntia is common when mother
      cladodes, planted during the dry spring season, develop young daughter cladodes
      that behave like C3 plants, with daytime stomatal opening and water loss. In
      contrast, wild Opuntia are less affected because daughter cladodes do not develop
      on them under extreme drought conditions. The main objective of this work is to
      evaluate the effects of the number of daughter cladodes on gas exchange
      parameters of mother cladodes of Opuntia ficus-indica exposed to varying soil
      water contents. METHODS: Rates of net CO2 uptake, stomatal conductance,
      intercellular CO2 concentration, chlorophyll content and relative water content
      were measured in mature mother cladodes with a variable number of daughter
      cladodes growing in spring under dry and wet conditions. KEY RESULTS: Daily
      carbon gain by mother cladodes was reduced as the number of daughter cladodes
      increased to eight, especially during drought. This was accompanied by decreased
      mother cladode relative water content, suggesting movement of water from mother
      to daughter cladodes. CO2 assimilation was most affected in phase IV of CAM (late
      afternoon net CO2 uptake) by the combined effects of daughter cladodes and
      drought. Rainfall raised the soil water content, decreasing the effects of
      daughter cladodes on net CO2 uptake by mother cladodes. CONCLUSIONS: Daughter
      cladodes significantly hasten the effects of drought on mother cladodes by
      competition for the water supply and thus decrease daily carbon gain by mother
      cladodes, mainly by inhibiting phase IV of CAM.

PMID- 15567806
TI  - Root system architecture of Quercus pubescens trees growing on different sloping
      conditions.
AB  - BACKGROUND AND AIMS: Plant roots' growth direction has important implications for
      plant development and survival; moreover it plays an effective and vital role in
      stabilizing weathered soil on a steep slope. The aim of this work was to assess
      the influence of slope on the architecture of woody root systems. METHODS: Five
      mature, single-stemmed Quercus pubescens trees growing on a steep slope and five
      on a shallow slope were excavated to a root diameter of 1 cm. A very precise
      numeric representation of the geometry and topology of structural root
      architecture was gained using a low-magnetic-field digitizing device (Fastrak,
      Polhemus). Several characteristics of root architecture were extracted by macros,
      including root volume, diameter, length, number, spatial position and branching
      order. KEY RESULTS: The diameter at breast height (dbh) was the best predictor of
      the root volume but had no correlation with length and number of roots. The slope
      affected the root volume for each branching order, and the basal cross-sectional
      area (CSA), number and length of the first-order roots. Number and length of the
      second- and third-order laterals were closely related in both conditions,
      although this relationship was closer in the shallow trees, suggesting the
      influence of a genetic control. Sloping trees showed a clustering tendency of the
      first- and second-order lateral roots in the up-slope direction, suggesting that
      the laterals rather than the taproots provide much of the anchorage. In a steep
      slope condition, the taproot tapering was positively correlated with the
      asymmetry magnitude of first-order roots, indicating compensation between taproot
      and main lateral roots' clustering tendency. CONCLUSIONS: These results suggest
      that on a slope, on clayey soils, root asymmetry appears to be a consequence of
      several environmental factors such as inclination, shallow-slides and soil
      compactness. In addition, this adaptive growth seems to counteract the turning
      moment induced by the self-loading forces acting in slope conditions, and as a
      consequence improves the tree stability.

PMID- 15567807
TI  - Multiple developmental pathways leading to a single morph: monosulcate pollen
      (examples from the Asparagales).
AB  - BACKGROUND AND AIMS: Early developmental events in microsporogenesis are known to
      play a role in pollen morphology: variation in cytokinesis type, cell wall
      formation, tetrad shape and aperture polarity are responsible for pollen aperture
      patterning. Despite the existence of other morphologies, monosulcate pollen is
      one of the most common aperture types in monocots, and is also considered as the
      ancestral condition in this group. It is known to occur from either a successive
      or a simultaneous cytokinesis. In the present study, the developmental sequence
      of microsporogenesis is investigated in several species of Asparagales that
      produce such monosulcate pollen, representing most families of this important
      monocot clade. METHODS: The developmental pathway of microsporogenesis was
      investigated using light transmission and epifluorescence microscopy for all
      species studied. Confocal microscopy was used to confirm centripetal cell plate
      formation. KEY RESULTS: Microsporogenesis is diverse in Asparagales, and most
      variation is generally found between families. It is confirmed that the whole
      higher Asparagales clade has a very conserved microsporogenesis, with a
      successive cytokinesis and centrifugal cell plate formation. Centripetal cell
      wall formation is described in Tecophilaeaceae and Iridaceae, a feature that had
      so far only been reported for eudicots. CONCLUSIONS: Monosulcate pollen can be
      obtained from several developmental pathways, leading thus to homoplasy in the
      monosulcate character state. Monosulcate pollen should not therefore be
      considered as the ancestral state unless it is produced through the ancestral
      developmental pathway. The question about the ancestral developmental pathway
      leading to monosulcy remains open.

PMID- 15567808
TI  - Variation in chromosome numbers, CMA bands and 45S rDNA sites in species of
      Selaginella (Pteridophyta).
AB  - BACKGROUND AND AIMS: Selaginella is the largest genus of heterosporous
      pteridophytes, but karyologically the genus is known only by the occurrence of a
      dysploid series of n=7-12, and a low frequency of polyploids. Aiming to
      contribute to a better understanding of the structural chromosomal variability of
      this genus, different staining methods were applied in species with different
      chromosome numbers. METHODS: The chromosome complements of seven species of
      Selaginella were analysed and, in four of them, the distribution of 45S rDNA
      sites was determined by fluorescent in situ hybridization. Additionally,
      CMA/DA/DAPI and silver nitrate staining were performed to investigate the
      correlation between the 45S rDNA sites, the heterochromatic bands and the number
      of active rDNA sites. KEY RESULTS: The chromosome numbers observed were 2n=18, 20
      and 24. The species with 2n=20 exhibited chromosome complement sizes smaller and
      less variable than those with 2n=18. The only species with 2n=24, S. convoluta,
      had relatively large and asymmetrical chromosomes. The interphase nuclei in all
      species were of the chromocentric type. CMA/DA/DAPI staining showed only a weak
      chromosomal differentiation of heterochromatic bands. In S. willdenowii and S.
      convoluta eight and six CMA+ bands were observed, respectively, but no DAPI+
      bands. The CMA+ bands corresponded in number, size and location to the rDNA
      sites. In general, the number of rDNA sites correlated with the maximum number of
      nucleoli per nucleus. Ten rDNA sites were found in S. plana (2n=20), eight in S.
      willdenowii (2n=18), six in S. convoluta (2n=24) and two in S. producta (2n=20).
      CONCLUSIONS: The remarkable variation in chromosome size and number and rDNA
      sites shows that dramatic karyological changes have occurred during the evolution
      of the genus at the diploid level. These data further suggest that the two
      putative basic numbers of the genus, x=9 and x=10, may have arisen two or more
      times independently.

PMID- 15567809
TI  - The GlideScope Video Laryngoscope: randomized clinical trial in 200 patients.
AB  - BACKGROUND: The GlideScope Video Laryngoscope is a new intubating device. It was
      designed to provide a view of the glottis without alignment of the oral,
      pharyngeal and tracheal axes. The aim of the study was to describe the use of the
      GlideScope in comparison with direct laryngoscopy for elective surgical patients
      requiring tracheal intubation. METHODS: Two hundred patients were randomly
      assigned to intubation by direct laryngoscopy using a Macintosh size 3 blade (DL,
      n=100) or intubation using the GlideScope (GS, n=100). Prior to intubation all
      patients were given a Cormack and Lehane (C&L) grade by a separate anaesthetist
      using a Macintosh size 3 blade. The patient was then intubated, using direct
      laryngoscopy or the GlideScope, by a different anaesthetist during which the
      larynx was inspected and given a laryngoscopy score. Time to intubate was
      measured. RESULTS: In the GS group, laryngoscopy grade was improved in the
      majority (28/41) of patients with C&L grade >1 and in all but one of patients who
      were grade 3 laryngoscopy (P<0.001). The overall mean time to intubate was 30
      (95% CI 28-33) s in the DL group and 46 (95% CI 43-49) s in the GS group. The
      time to intubate for C&L grade 3 was similar in both groups, being 47 s for the
      DL group and 50 s for the GS group respectively. CONCLUSION: In most patients,
      the GlideScope provided a laryngoscopic view equal to or better than that of
      direct laryngoscopy, but it took an additional 16 s (average) for tracheal
      intubation. It has potential advantages over standard direct laryngoscopy for
      difficult intubations.

PMID- 15567810
TI  - Double-blind randomized controlled trial to determine extent of amnesia with
      midazolam given immediately before general anaesthesia.
AB  - BACKGROUND: Anterograde, but not retrograde, amnesia has been demonstrated
      following midazolam administration. However, there have been no studies
      investigating whether or not immediate retrograde amnesia can be produced with
      midazolam. METHODS: After ethics committee approval and consent, 40 adult
      patients undergoing surgery and general anaesthesia were randomly allocated to
      one of four groups: midazolam 2 mg, midazolam 5 mg, midazolam 10 mg or control
      (normal saline). Measurements were made from 12 min prior to induction of
      anaesthesia, and the study drug was administered 8 min prior to induction of
      anaesthesia. Midazolam effects were measured using visual recognition of posters,
      recall of specific events, bispectral index (BIS) and sedation visual analogue
      score. RESULTS: Recognition and recall rates were similar between groups up until
      the time of study drug administration, with no evidence of retrograde amnesia
      (all P>0.3). There was a dose-dependent deterioration in visual recall (P=0.002),
      event recollection (P<0.001), BIS (P<0.001) and sedation score (P<0.001)
      following i.v. midazolam when compared with control. CONCLUSIONS: We found no
      evidence that i.v. midazolam 2-10 mg produces immediate retrograde amnesia.
      Midazolam causes anterograde amnesia in a dose-responsive manner.

PMID- 15567811
TI  - Influence of working conditions on job satisfaction in anaesthetists.
AB  - BACKGROUND: We studied job satisfaction, physical health, emotional well-being
      and working conditions in 125 Austrian and Swiss anaesthetists. METHODS:
      Responses to self-reporting questionnaires were evaluated. Dependent variables
      included job satisfaction, emotional well-being and physical health. Independent
      variables included age, sex, marital status, position and working conditions as
      assessed by the Instrument for Stress-related Job Analysis. RESULTS: Control over
      work shows a strong effect on job satisfaction in anaesthetists, for example
      influence on handling tasks (P=0.001), time control (P=0.002) and participation
      (P=0.001), whereas task demands and task-related problems did not have any
      effect. Anaesthetists in leading positions and specialists reported lower job
      satisfaction (P=0.012) than did anaesthetists in non-leading positions. Job
      satisfaction was associated with better physical health (P=0.001) and better
      emotional well-being (P=0.005). CONCLUSIONS: Our results suggest that a high
      level of job satisfaction in anaesthetists correlates with interesting work
      demands and the opportunity to contribute skills and ideas. To improve job
      satisfaction, more attention should be paid to improving working conditions,
      including control over decision-making, and allowing anaesthetists to have more
      influence on their own work pace and work schedule.

PMID- 15567812
TI  - Evaluation of genitofemoral nerve block, in addition to ilioinguinal and
      iliohypogastric nerve block, during inguinal hernia repair in children.
AB  - BACKGROUND: Ilioinguinal and iliohypogastric (IG-IH) nerve block has been widely
      used in children undergoing inguinal hernia repair. This technique may provide
      insufficient analgesia for intraoperative management as the inguinal region may
      receive sensory innervation from genitofemoral nerve. We proposed that addition
      of a genitofemoral nerve block might improve the quality of analgesia. METHODS:
      Ninety-eight children undergoing inguinal hernia repair were assigned randomly to
      receive either IG-IH nerve block (Group I) or IG-IH and genitofemoral nerve
      blocks (Group II). Systolic arterial pressure (SAP) and heart rate (HR) were
      recorded before surgery (control), after skin incision, at sac traction and at
      the end of surgery. Postoperative analgesic requirements and incidence of
      complications were recorded until discharge. RESULTS: At sac traction, SAP and HR
      were significantly higher in Group I (P<0.05), and the incidence of episodes of
      increased HR was also significantly higher in Group II (29 vs 12%, respectively,
      P<0.05). There were no significant differences in SAP and HR at other time
      points, postoperative analgesic requirements or incidence of complications
      between the groups. CONCLUSIONS: The benefit of the additional genitofemoral
      nerve block to IG-IH nerve block was limited only to the time of sac traction
      without any postoperative effect. This suggests there is little clinical benefit
      in the addition of a genitofemoral nerve block.

PMID- 15567813
TI  - Double-blind comparison of intrapleural saline and 0.25% bupivacaine for
      ipsilateral shoulder pain after thoracotomy in patients receiving thoracic
      epidural analgesia.
AB  - BACKGROUND: The aim of this prospective double-blind randomized placebo
      controlled study was to investigate the effect of intrapleural bupivacaine on
      ipsilateral post-thoracotomy shoulder pain in patients receiving thoracic
      epidural analgesia. METHODS: Of the 68 patients recruited to the study, 41(60%)
      developed ipsilateral shoulder pain within 2 h of surgery. These patients were
      randomly assigned to receive either 40 ml of intrapleural bupivacaine 0.25% with
      epinephrine 1:200 000 or 40 ml of intrapleural saline. The study solution was
      injected into the tube of a basal drain that had been clamped distal to the site
      of administration. Shoulder pain at rest and on coughing was assessed using a
      visual analogue scale (VAS) and an observer verbal rating score (OVRS)
      immediately before and 30 min, 1 h, 2 h, 3 h and 4 h after intrapleural
      bupivacaine/saline. The total volume of epidural solution administered was
      recorded. RESULTS: Thirty-nine patients completed the study and were included in
      the analysis. There were no significant differences in baseline characteristics
      between the two groups. There were no significant differences between groups for
      VAS or OVRS pain scores at rest or with cough at any of the six assessment times.
      The total volumes of epidural solution administered to the bupivacaine and saline
      groups were 56 ml and 48 ml, respectively. This difference was not significant.
      CONCLUSION: Intrapleural administration of 40 ml of bupivacaine 0.25% does not
      provide effective pain relief for ipsilateral post-thoracotomy shoulder pain.

PMID- 15567814
TI  - Rheumatoid and psoriatic knee synovitis: clinical, grey scale, and power Doppler
      ultrasound assessment of the response to etanercept.
AB  - OBJECTIVE: To determine the effect of tumour necrosis factor alpha (TNFalpha)
      blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid
      and psoriatic arthritis, by local and systemic disease activity assessment and
      combined grey scale and power Doppler ultrasonographic monitoring. METHODS: 27
      knees affected by rheumatoid KJS (n = 12) and psoriatic KJS (n = 8) were assessed
      before receiving treatment and at 3 and 12 months' follow up. Time dependent
      clinical changes in disease activity were monitored by C reactive protein,
      erythrocyte sedimentation rate (ESR), global health status (GHS), and Ritchie
      (RAI) and knee joint articular (KJAI) indices; synovial changes were monitored by
      ultrasonographic and power Doppler indices for grey scale synovial thickening and
      for distinct intrasynovial vessel power Doppler flow configurations
      (fluid/synovium interface (F/SI-PD) and pannus/cartilage interface (P/CI-PD)).
      Interobserver and intraobserver variability of grey scale and power Doppler
      ultrasonographic was evaluated. Response to treatment was assessed by analysis of
      variance for repeated measures on clinical and ultrasonographic variables.
      RESULTS: Rapid (3 months) reduction in F/SI-PD flow (p<0.001), parallel to
      reductions of C reactive protein (p<0.05), ESR (p<0.001), KJAI (p<0.002), RAI,
      and GHS (p<0.001), was sustained at 12 months when it was accompanied by
      reduction in both synovial thickening and P/CI-PD flow (p<0.001). No differences
      (ANOVA) were noted at baseline or at 12 months in clinical and ultrasonographic
      variables between either the rheumatoid or the psoriatic KJS groups. CONCLUSION:
      Grey scale and power Doppler ultrasonography are reliable measures of long term
      change in rheumatoid and psoriatic KJS disease activity in response to anti
      TNFalpha treatment with etanercept.

PMID- 15567815
TI  - Increased expression of humanin peptide in diffuse-type pigmented villonodular
      synovitis: implication of its mitochondrial abnormality.
AB  - OBJECTIVES: To define the pathogenesis of pigmented villonodular synovitis
      (PVNS), by searching for highly expressed genes in primary synovial cells from
      patients with PVNS. METHODS: A combination of subtraction cloning and Southern
      colony hybridisation was used to detect highly expressed genes in PVNS in
      comparison with rheumatoid synovial cells. Northern hybridisation was performed
      to confirm the differential expression of the humanin gene in PVNS. Expression of
      the humanin peptide was analysed by western blotting and immunohistochemistry.
      Electron microscopic immunohistochemistry was performed to investigate the
      distribution of this peptide within the cell. RESULTS: 68 highly expressed genes
      were identified in PVNS. Humanin genes were strongly expressed in diffuse-type
      PVNS, but were barely detected in nodular-type PVNS, rheumatoid arthritis, or
      osteoarthritis. Humanin peptide was identified in synovium from diffuse-type
      PVNS, and most of the positive cells were distributed in the deep layer of the
      synovial tissue. Double staining with anti-humanin and anti-heat shock protein 60
      showed that humanin was expressed mainly in mitochondria. Electron microscopy
      disclosed immunolocalisation of this peptide, predominantly around dense iron
      deposits within the siderosome. CONCLUSIONS: Increased expression of the humanin
      peptide in mitochondria and siderosomes is characteristic of synovial cells from
      diffuse-type PVNS. Humanin is an anti-apoptotic peptide which is encoded in the
      mitochondrial genome. Present findings suggest that mitochondrial dysfunction may
      be the principal factor in pathogenesis of diffuse-type PVNS and that humanin
      peptide may play a part in the neoplastic process in this form of PVNS.

PMID- 15567816
TI  - A two-way bioinformatic street.

PMID- 15567817
TI  - U.S. national academies. Advice on science advising leaves plenty of questions.

PMID- 15567818
TI  - Paleoanthropology. Skeptic to take possession of Flores hominid bones.

PMID- 15567819
TI  - Scholarly publishing. NIH flooded with comments on public access proposal.

PMID- 15567820
TI  - Obesity research. New data on appetite-suppressing peptide challenge critics.

PMID- 15567821
TI  - Evolution. Ice ages may explain ancient bison's boom-bust history.

PMID- 15567822
TI  - Medicine. Bone marrow cells: the source of gastric cancer?

PMID- 15567823
TI  - Biochemistry. Immune cells speed the evolution of novel proteins.

PMID- 15567825
TI  - Particle physics. Neutrinos are all flip-floppers, Japanese study shows.

PMID- 15567824
TI  - Agriculture. China could be first nation to approve sale of GM rice.

PMID- 15567826
TI  - European science. New commissioner calls for evolution, not revolution.

PMID- 15567827
TI  - Theoretical physics. String theory gets real--sort of.

PMID- 15567828
TI  - Theoretical physics. The children of the revolution.

PMID- 15567829
TI  - U.S. science policy. What can NIH do for physicists?

PMID- 15567830
TI  - Middle East. X-ray source produces a glimmer of hope.

PMID- 15567831
TI  - Society of Vertebrate Paleontology meeting. Head games show whether dinos went on
      two legs or four.

PMID- 15567832
TI  - Society of Vertebrate Paleontology meeting. Antiextinction tip: eat to live.

PMID- 15567833
TI  - Society of Vertebrate Paleontology meeting. Timing complicates history of horses.

PMID- 15567834
TI  - Society of Vertebrate Paleontology meeting. Snapshots from the meeting.

PMID- 15567835
TI  - Using stimulants in children with ADHD.

PMID- 15567836
TI  - Outbreak of West Nile virus in North America.

PMID- 15567837
TI  - Mouse biology at Monterotondo.

PMID- 15567838
TI  - Beauty, art, and foreplay?

PMID- 15567839
TI  - Comment on "Enhanced open ocean storage of CO2 from shelf sea pumping".

PMID- 15567841
TI  - Social psychology. Why ordinary people torture enemy prisoners.

PMID- 15567842
TI  - Molecular biology. A higher order of silence.

PMID- 15567843
TI  - Physics. What is dark matter made of?

PMID- 15567844
TI  - Ecology. Oh the locusts sang, then they dropped dead.

PMID- 15567845
TI  - Planetary science. Nothing simple about asteroids.

PMID- 15567846
TI  - Evolution. Epistasis in RNA viruses.

PMID- 15567848
TI  - Common and distinct elements in cellular signaling via EGF and FGF receptors.
AB  - Signaling pathways that are activated by epidermal growth factor (EGF) or
      fibroblast growth factor (FGF) receptors have been identified and compared
      (detailed Connections Maps are available at Science's Signal Transduction
      Knowledge Environment). Both receptors stimulate a similar complement of
      intracellular signaling pathways. However, whereas activated EGF receptors
      (EGFRs) function as the main platform for recruitment of signaling proteins,
      signaling through the FGF receptors (FGFRs) is mediated primarily by assembly of
      a multidocking protein complex. Moreover, FGFR signaling is subject to additional
      intracellular and extracellular control mechanisms that do not affect EGFR
      signaling. The differential circuitry of the intracellular networks that are
      activated by EGFR and FGFR may affect signal specificity and physiological
      responses.

PMID- 15567849
TI  - Pheromone signaling mechanisms in yeast: a prototypical sex machine.
AB  - The actions of many extracellular stimuli are elicited by complexes of cell
      surface receptors, heterotrimeric guanine nucleotide-binding proteins (G
      proteins), and mitogen-activated protein (MAP) kinase complexes. Analysis of
      haploid yeast cells and their response to peptide mating pheromones has produced
      important advances in our understanding of G protein and MAP kinase signaling
      mechanisms. Many of the components, their interrelationships, and their
      regulators were first identified in yeast. Current analysis of the pheromone
      response pathway (see the Connections Maps at Science's Signal Transduction
      Knowledge Environment) will benefit from new and powerful genomic, proteomic, and
      computational approaches that will likely reveal additional general principles
      that are applicable to more complex organisms.

PMID- 15567850
TI  - Jekyll and Hyde in the microbial world.
AB  - Fungi are nonmotile organisms that obtain carbon from compounds in their
      immediate surroundings. Confronted with nutrient limitation, the yeast
      Saccharomyces cerevisiae undergoes a dimorphic transition, switching from
      spherical cells to filaments of adherent, elongated cells that can invade the
      substratum. A complex web of sensing mechanisms and cooperation among signaling
      networks (including a mitogen-activated protein kinase cascade, cyclic adenosine
      monophosphate-dependent protein kinase, and 5'-adenosine monophosphate-activated
      protein kinase) elicits the appropriate changes in physiology, cell cycle
      progression, cell polarity, and gene expression to achieve this differentiation.
      Highly related signaling processes control filamentation and virulence of many
      human fungal pathogens.

PMID- 15567851
TI  - When the stress of your environment makes you go HOG wild.
AB  - When exposed to increased dissolved solute in their environment (hyperosmotic
      stress), all eukaryotic cells respond by rapidly activating a conserved mitogen
      activated protein kinase cascade, known in budding yeast Saccharomyces cerevisiae
      as the high osmolarity glycerol (HOG) pathway. Intensive genetic and biochemical
      analysis in this organism has revealed the presumptive osmosensors, downstream
      signaling components, and metabolic and transcriptional changes that allow cells
      to cope with this stressful condition. These findings have had direct application
      to understanding stress sensing and control of transcription by stress-activated
      mitogen-activated protein kinases in mammalian cells.

PMID- 15567852
TI  - The ethylene signaling pathway.
AB  - Plants use a structurally very simple gas molecule, the hydrocarbon ethylene, to
      modulate various developmental programs and coordinate responses to a multitude
      of external stress factors. How this simple molecule generates such a diverse
      array of effects has been the subject of intense research for the past two
      decades. A fascinating signaling pathway, with classical as well as novel plant
      specific signaling elements, is emerging from these studies. We describe the four
      main modules that constitute this signaling pathway: a phosphotransfer relay, an
      EIN2-based unit, a ubiquitin-mediated protein degradation component, and a
      transcriptional cascade. The canonical and Arabidopsis ethylene signaling
      pathways in the Signal Transduction Knowledge Environment Connections Maps
      provide a complete panoramic view of these signaling events in plants.

PMID- 15567853
TI  - Keeping the leaves green above us.
AB  - The plant immune system relies to a great extent on the highly regulated
      expression of hundreds of defense genes encoding antimicrobial proteins, such as
      defensins, and antiherbivore proteins, such as lectins. The expression of many of
      these genes is controlled by a family of mediators known as jasmonates; these
      cyclic oxygenated fatty acid derivatives are reminiscent of prostaglandins. The
      roles of jasmonates also extend to the control of reproductive development. How
      are these complex events regulated? Nearly 20 members of the jasmonate family
      have been characterized. Some, like jasmonic acid, exist in unmodified forms,
      whereas others are conjugated to other lipids or to hydrophobic amino acids. Why
      do so many chemically different forms of these mediators exist, and do individual
      jasmonates have unique signaling properties or are they made to facilitate
      transport within and between cells? Key features of the jasmonate signal pathway
      have been identified and include the specific activation of E3-type ubiquitin
      ligases thought to target as-yet-undescribed transcriptional repressors for
      modification or destruction. Several classes of transcription factor are known to
      function in the jasmonate pathway, and, in some cases, these proteins provide
      nodes that integrate this network with other important defensive and
      developmental pathways. Progress in jasmonate research is now rapid, but large
      gaps in our knowledge exist. Aimed to keep pace with progress, the ensemble of
      jasmonate Connections Maps at the Signal Transduction Knowledge Environment
      describe (i) the canonical signaling pathway, (ii) the Arabidopsis signaling
      pathway, and (iii) the biogenesis and structures of the jasmonates themselves.

PMID- 15567854
TI  - Natural killer cell signaling pathways.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that are
      involved in the early defenses against foreign cells, as well as autologous cells
      undergoing various forms of stress, such as microbial infection or tumor
      transformation. NK cell activation is controlled by a dynamic balance between
      complementary and antagonistic pathways that are initiated upon interaction with
      potential target cells. NK cells express an array of activating cell surface
      receptors that can trigger cytolytic programs, as well as cytokine or chemokine
      secretion. Some of these activating cell surface receptors initiate protein
      tyrosine kinase (PTK)-dependent pathways through noncovalent associations with
      transmembrane signaling adaptors that harbor intracytoplasmic ITAMs
      (immunoreceptor tyrosine-based activation motifs). Additional cell surface
      receptors that are not directly coupled to ITAMs also participate in NK cell
      activation. These include NKG2D, which is noncovalently associated to the DAP10
      transmembrane signaling adaptor, as well as integrins and cytokine receptors. NK
      cells also express cell surface inhibitory receptors that antagonize activating
      pathways through protein tyrosine phosphatases (PTPs). These inhibitory cell
      surface receptors are characterized by intracytoplasmic ITIMs (immunoreceptor
      tyrosine-based inhibition motifs). The tyrosine-phosphorylation status of several
      signaling components that are substrates for both PTKs and PTPs is thus key to
      the propagation of the NK cell effector pathways. Understanding the integration
      of these multiple signals is central to the understanding and manipulation of NK
      cell effector signaling pathways.

PMID- 15567855
TI  - Stokes drag on a sphere in a nematic liquid crystal.
AB  - The Stokes-Einstein relation relates the diffusion coefficient of a spherical
      Brownian particle in a viscous fluid to its friction coefficient. For a particle
      suspended in anisotropic liquid, theory predicts that the drag coefficient should
      also be anisotropic. Using video microscopy coupled with particle tracking
      routines, the Brownian fluctuations of micrometer-sized particles were analyzed
      to yield a quantitative measurement of the diffusion coefficients parallel and
      perpendicular to the nematic director. The experimental values agree quite well
      with recent numerical calculations that take into account the distortions of the
      director field in the vicinity of the particles.

PMID- 15567856
TI  - Impact-induced seismic activity on asteroid 433 Eros: a surface modification
      process.
AB  - High-resolution images of the surface of asteroid 433 Eros revealed evidence of
      downslope movement of a loose regolith layer, as well as the degradation and
      erasure of small impact craters (less than approximately 100 meters in diameter).
      One hypothesis to explain these observations is seismic reverberation after
      impact events. We used a combination of seismic and geomorphic modeling to
      analyze the response of regolith-covered topography, particularly craters, to
      impact-induced seismic shaking. Applying these results to a stochastic cratering
      model for the surface of Eros produced good agreement with the observed size
      frequency distribution of craters, including the paucity of small craters.

PMID- 15567857
TI  - Periodic mesoporous dendrisilicas.
AB  - We report the synthesis of a new class of materials called periodic mesoporous
      dendrisilicas. They are prepared from dendrimers with trialkoxysilyl groups at
      the outmost shell. Dendrimers of various cores and numbers of shells are used.
      The dendrisilica synthesis is based on acid- or base-catalyzed hydrolysis of the
      trialkoxysilyl groups and subsequent template-directed condensation of the
      dendrimers into an ordered template-dendrisilica nanocomposite. The template can
      be removed with organic solvents, producing a periodic mesoporous dendrisilica
      whose pore walls consist of interconnected dendrimer building blocks.

PMID- 15567858
TI  - A reversible synthetic rotary molecular motor.
AB  - The circumrotation of a submolecular fragment in either direction in a synthetic
      molecular structure is described. The movement of a small ring around a larger
      one occurs through positional displacements arising from biased Brownian motion
      that are kinetically captured and then directionally released. The sense of
      rotation is governed solely by the order in which a series of orthogonal chemical
      transformations is performed. The minimalist nature of the [2]catenane flashing
      ratchet design permits certain mechanistic comparisons with the Smoluchowski
      Feynman ratchet and pawl. Even when no work has to be done against an opposing
      force and no net energy is used to power the motion, a finite conversion of
      energy is intrinsically required for the molecular motor to undergo directional
      rotation. Nondirectional rotation has no such requirement.

PMID- 15567859
TI  - Three-dimensional hydrogen microscopy in diamond.
AB  - A microprobe of protons with an energy of 17 million electron volts is used to
      quantitatively image three-dimensional hydrogen distributions at a lateral
      resolution better than 1 micrometer with high sensitivity. Hydrogen images of a
      <110>-textured undoped polycrystalline diamond film show that most of the
      hydrogen is located at grain boundaries. The average amount of hydrogen atoms
      along the grain boundaries is (8.1 +/- 1.5) x 10(14) per square centimeter,
      corresponding to about a third of a monolayer. The hydrogen content within the
      grain is below the experimental sensitivity of 1.4 x 10(16) atoms per cubic
      centimeter (0.08 atomic parts per million). The data prove a low hydrogen content
      within chemical vapor deposition-grown diamond and the importance of hydrogen at
      grain boundaries, for example, with respect to electronic properties of
      polycrystalline diamond.

PMID- 15567860
TI  - Seismic anisotropy beneath Ruapehu volcano: a possible eruption forecasting tool.
AB  - The orientation of crustal seismic anisotropy changed at least twice by up to 80
      degrees because of volcanic eruptions at Ruapehu Volcano, New Zealand. These
      changes provide the basis for a new monitoring technique and possibly for future
      midterm eruption forecasting at volcanoes. The fast anisotropic direction was
      measured during three seismometer deployments in 1994, 1998, and 2002, providing
      an in situ measurement of the stress in the crust under the volcano. The stress
      direction changed because of an eruption in 1995-1996. Our 2002 measurements
      revealed a partial return to the pre-eruption stress state. These changes were
      probably caused by repeated filling and depressurizing of a magmatic dike system.

PMID- 15567861
TI  - Evidence for positive epistasis in HIV-1.
AB  - Reproductive strategies such as sexual reproduction and recombination that
      involve the shuffling of parental genomes for the production of offspring are
      ubiquitous in nature. However, their evolutionary benefit remains unclear. Many
      theories have identified potential benefits, but progress is hampered by the
      scarcity of relevant data. One class of theories is based on the assumption that
      mutations affecting fitness exhibit negative epistasis. Retroviruses recombine
      frequently and thus provide a unique opportunity to test these theories. Using
      amino acid sequence data and fitness values from 9466 human immunodeficiency
      virus 1 (HIV-1) isolates, we find in contrast to these theories strong
      statistical evidence for a predominance of positive epistasis in HIV-1.

PMID- 15567862
TI  - A probabilistic functional network of yeast genes.
AB  - A conceptual framework for integrating diverse functional genomics data was
      developed by reinterpreting experiments to provide numerical likelihoods that
      genes are functionally linked. This allows direct comparison and integration of
      different classes of data. The resulting probabilistic gene network estimates the
      functional coupling between genes. Within this framework, we reconstructed an
      extensive, high-quality functional gene network for Saccharomyces cerevisiae,
      consisting of 4681 (approximately 81%) of the known yeast genes linked by
      approximately 34,000 probabilistic linkages comparable in accuracy to small-scale
      interaction assays. The integrated linkages distinguish true from false-positive
      interactions in earlier data sets; new interactions emerge from genes' network
      contexts, as shown for genes in chromatin modification and ribosome biogenesis.

PMID- 15567863
TI  - Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in
      atherogenesis.
AB  - In vitro studies suggest a role for c-Jun N-terminal kinases (JNKs) in
      proatherogenic cellular processes. We show that atherosclerosis-prone ApoE-/-
      mice simultaneously lacking JNK2 (ApoE-/- JNK2-/- mice), but not ApoE-/- JNK1-/-
      mice, developed less atherosclerosis than do ApoE-/- mice. Pharmacological
      inhibition of JNK activity efficiently reduced plaque formation. Macrophages
      lacking JNK2 displayed suppressed foam cell formation caused by defective uptake
      and degradation of modified lipoproteins and showed increased amounts of the
      modified lipoprotein-binding and -internalizing scavenger receptor A (SR-A),
      whose phosphorylation was markedly decreased. Macrophage-restricted deletion of
      JNK2 was sufficient to decrease atherogenesis. Thus, JNK2-dependent
      phosphorylation of SR-A promotes uptake of lipids in macrophages, thereby
      regulating foam cell formation, a critical step in atherogenesis.

PMID- 15567864
TI  - Rise and fall of the Beringian steppe bison.
AB  - The widespread extinctions of large mammals at the end of the Pleistocene epoch
      have often been attributed to the depredations of humans; here we present genetic
      evidence that questions this assumption. We used ancient DNA and Bayesian
      techniques to reconstruct a detailed genetic history of bison throughout the late
      Pleistocene and Holocene epochs. Our analyses depict a large diverse population
      living throughout Beringia until around 37,000 years before the present, when the
      population's genetic diversity began to decline dramatically. The timing of this
      decline correlates with environmental changes associated with the onset of the
      last glacial cycle, whereas archaeological evidence does not support the presence
      of large populations of humans in Eastern Beringia until more than 15,000 years
      later.

PMID- 15567865
TI  - Periodical cicadas as resource pulses in North American forests.
AB  - Resource pulses are occasional events of ephemeral resource superabundance that
      occur in many ecosystems. Aboveground consumers in diverse communities often
      respond strongly to resource pulses, but few studies have investigated the
      belowground consequences of resource pulses in natural ecosystems. This study
      shows that resource pulses of 17-year periodical cicadas (Magicicada spp.)
      directly increase microbial biomass and nitrogen availability in forest soils,
      with indirect effects on growth and reproduction in forest plants. These findings
      suggest that pulses of periodical cicadas create "bottom-up cascades," resulting
      in strong and reciprocal links between the aboveground and belowground components
      of a North American forest ecosystem.

PMID- 15567866
TI  - Gastric cancer originating from bone marrow-derived cells.
AB  - Epithelial cancers are believed to originate from transformation of tissue stem
      cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited
      to sites of tissue injury and inflammation, might also represent a potential
      source of malignancy. We show that although acute injury, acute inflammation, or
      transient parietal cell loss within the stomach do not lead to BMDC recruitment,
      chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces
      repopulation of the stomach with BMDCs. Subsequently, these cells progress
      through metaplasia and dysplasia to intraepithelial cancer. These findings
      suggest that epithelial cancers can originate from marrow-derived sources and
      thus have broad implications for the multistep model of cancer progression.

PMID- 15567867
TI  - Nucleosome arrays reveal the two-start organization of the chromatin fiber.
AB  - Chromatin folding determines the accessibility of DNA constituting eukaryotic
      genomes and consequently is profoundly important in the mechanisms of nuclear
      processes such as gene regulation. Nucleosome arrays compact to form a 30
      nanometer chromatin fiber of hitherto disputed structure. Two competing classes
      of models have been proposed in which nucleosomes are either arranged linearly in
      a one-start higher order helix or zigzag back and forth in a two-start helix. We
      analyzed compacted nucleosome arrays stabilized by introduction of disulfide
      cross-links and show that the chromatin fiber comprises two stacks of nucleosomes
      in accord with the two-start model.

PMID- 15567868
TI  - Chromatin compaction by a polycomb group protein complex.
AB  - Polycomb group proteins preserve body patterning through development by
      maintaining transcriptional silencing of homeotic genes. A long-standing
      hypothesis is that silencing involves creating chromatin structure that is
      repressive to gene transcription. We demonstrate by electron microscopy that core
      components of Polycomb Repressive Complex 1 induce compaction of defined
      nucleosomal arrays. Compaction by Polycomb proteins requires nucleosomes but not
      histone tails. Each Polycomb complex can compact about three nucleosomes. A
      region of Posterior Sex Combs that is important for gene silencing in vivo is
      also important for chromatin compaction, linking the two activities. This
      mechanism of chromatin compaction might be central to stable gene silencing by
      the Polycomb group.

PMID- 15567869
TI  - Commentary: Nitrites, nitrates and nitrosation as causes of brain cancer in
      children: epidemiological challenges.

PMID- 15567870
TI  - Biological theories, evidence, and epidemiology.

PMID- 15567871
TI  - Commentary: Can conventional migration studies really identify critical age
      period effects?

PMID- 15567872
TI  - Childhood migration and cardiovascular risk.
AB  - BACKGROUND: Childhood living conditions have been hypothesized to be associated
      with the development of cardiovascular diseases and diabetes mellitus in adult
      life. METHODS: We analysed, using logistic regression, the risk of self-reported
      diabetes, hypertension, hyperlipidaemia, and ischaemic heart disease in a
      population-based sample of 3643 Chinese men and 3778 Chinese women some of whom
      had experienced a change to more favourable economic conditions at different life
      stages through migration from mainland China to Hong Kong. RESULTS: Adjusting for
      socio-economic status, risk behaviours, and family history, the development of
      diabetes was associated with migration from China to Hong Kong in the first two
      decades of life, albeit with a decreasing intensity of effect (OR = 2.02, 95% CI:
      1.18, 3.45, OR = 1.84, 95% CI: 1.27, 2.66, and OR = 1.72, 95% CI: 1.21, 2.45 for
      migration at ages 0-7, 8-17, and 18-24, respectively). The development of
      hypertension was mostly susceptible to environmental change during the growth
      spurt and puberty (migration at ages 8-17 OR = 1.56, 95% CI: 1.22, 1.99). The
      development of heart disease was associated with a sex-specific critical period
      in early childhood for men (migration at ages 0-7 OR = 3.17, 95% CI: 1.70, 5.91).
      CONCLUSION: Environmental change by migration throughout the first two decades of
      life can affect the development of diabetes, hypertension, hyperlipidaemia, and
      ischaemic heart disease, although adverse childhood conditions alone may not be a
      risk factor. Our results suggest that specific life course pathways may pre
      dispose to these conditions and could be relevant to their aetiology in
      populations undergoing rapid development.

PMID- 15567873
TI  - Household water source and the risk of childhood brain tumours: results of the
      SEARCH International Brain Tumor Study.
AB  - BACKGROUND: The period in utero is a time of increased vulnerability. Offspring
      of pregnant women exposed to carcinogenic substances in drinking water may be
      more likely to develop cancer. We examined whether household water source and the
      presence of nitrates or nitrites in residential water were associated with
      increased risks of childhood brain tumours (CBT). METHODS: We used data from a
      multicentre, case-control study with maternal information on residential water
      source, and nitrate/nitrite levels of tap water measured by dipstick. Subjects
      included 836 CBT cases and 1485 controls from five countries. RESULTS: The risks
      of CBT associated with reliance on well water (versus public water) during
      pregnancy varied widely, with significantly increased risks noted in two (of
      seven) regions and a decreased risk observed in one region. CBT risk did not
      increase with increasing nitrate levels. However, our results based on tap water
      tested in the pregnancy residences suggest the risk of astrocytoma may be
      associated with increasing levels of nitrite (odds ratio [OR] = 4.3, 95% CI: 1.4,
      12.6 for nitrite levels of 1-<5 mg/l nitrite ion; OR = 5.7, 95% CI: 1.2, 27.2 of
      nitrite > or =5 mg/l). CONCLUSIONS: These results should be interpreted with
      caution because women's recollection of water sources may have contained
      inaccuracies, and nitrate and nitrite measurements, available for only a portion
      of subjects, were often obtained years after the pregnancies occurred. However,
      our results suggest a need for closer evaluation of well water content in some
      regions and the possibility that a nitrite-related water exposure may be
      associated with CBT.

PMID- 15567874
TI  - Presurgical diagnosis of posterior deep infiltrating endometriosis based on a
      standardized questionnaire.
AB  - BACKGROUND: To derive a diagnostic model based on symptoms and history as
      assessed by a standardized questionnaire to predict posterior deep infiltrating
      endometriosis (DIE) among women with chronic pelvic pain symptoms. METHODS: 134
      women scheduled for laparoscopy for chronic pelvic pain symptoms completed a
      standardized self-administered questionnaire, specifically designed for the
      study. We compared the symptoms of the women with posterior DIE diagnosed at
      laparoscopy with those of the women with other disorders, and used multiple
      logistic regression analysis to select the best combination of symptoms for
      predicting posterior DIE. Cross-validation was performed with the jackknife
      method. RESULTS: 51 women (38.1%) were diagnosed with posterior DIE and 83 with
      other disorders (61.9%). The following variables were independent predictors for
      posterior DIE: painful defecation during menses, severe dyspareunia (visual
      analogic scale > or =8), pain other than noncyclic, and previous surgery for
      endometriosis. The cross-validation procedure leads to a simplified diagnostic
      model that uses two independent predictors: painful defecation during menses and
      severe dyspareunia. The sensitivity of this model for diagnosing posterior DIE
      was 74.5%, its specificity was 68.7%, its positive likelihood ratio was 2.4, and
      its negative likelihood ratio was 0.4. It correctly classified 70.9% of our
      sample into a high-risk (with either severe dyspareunia or painful defecation
      during menses) and a low-risk (neither symptom) group. CONCLUSIONS: Standardized
      evaluation of painful symptoms is useful for screening women so that they may
      have adequate exploration and counselling before laparoscopic surgery for pelvic
      pain symptoms.

PMID- 15567875
TI  - Prevalence of chromosomal abnormalities in 2078 infertile couples referred for
      assisted reproductive techniques.
AB  - BACKGROUND: This study analyses the prevalence of karyotype changes and Yq11
      microdeletions among couples referred for assisted reproduction techniques.
      METHODS: Prior to receiving either IVF or ICSI treatment, each partner of 2078
      infertile couples was screened for karyotype changes by GTG-banding technique on
      peripheral lymphocytes. No subject presented with obvious phenotype of
      chromosomal rearrangement. All the oligo/azoospermic men with normal karyotype
      were further investigated by PCR for Yq11 microdeletions. RESULTS: Eighty-two out
      of 2078 couples (3.95%) had one partner carrying a chromosomal change, and 10 out
      of 202 (4.95%) men showed Yq11 microdeletions. The chromosomal rearrangements
      were 44 (2.1%) translocations, 23 (1.1%) gonosomal mosaics, six (0.3%) 47,XXY,
      five (0.24%) marker chromosomes, three (0.14%) inversions and one (0.05%)
      duplication. Frequency of anomalies in men and women were similar: 42 and 40
      cases respectively. CONCLUSIONS: Partners of infertile couples requiring IVF or
      ICSI treatment appear to be affected by higher frequency of chromosomal
      rearrangements than the general population. Categories with greater risk were
      represented by men with sperm cell count <20 x 10(6) sperm/ml, and women with
      history of pregnancy loss.

PMID- 15567876
TI  - Can we eliminate severe ovarian hyperstimulation syndrome?
AB  - The desire of some couples for children is so strong that they are willing to
      accept a modicum of risk to treat their infertility. Ideally, assisted
      reproduction technology practitioners seek a balance between optimum ovarian
      stimulation and successful treatment outcome with minimal rate of severe ovarian
      hyperstimulation syndrome (OHSS) or multiple pregnancies. However, despite many
      years of clinical experience, there are no precise methods to completely prevent
      severe OHSS, except by withholding the ovulation-inducing trigger of hCG.
      Individualization of treatment according to the specific risk factor and the
      specific response in the current cycle with the option of freezing of all
      embryos, or replacement of only a single embryo, has the potential of reducing
      the risk and the severity of the syndrome in susceptible cases. We offer a triage
      aimed at eliminating the occurrence of severe ovarian hyperstimulation syndrome
      on the basis of several clinical observations, including the role of GnRH
      antagonist in controlled ovarian stimulation protocols, the option of freezing of
      all embryos, or replacement of only a single embryo in the blastocyst stage.

PMID- 15567877
TI  - Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude
      mouse model of endometriosis.
AB  - BACKGROUND: Women with endometriosis have elevated levels of cyclooxygenase-2
      (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2
      has been shown to reduce inflammation, angiogenesis and cellular proliferation.
      It may also downregulate aromatase activity in ectopic endometrial lesions.
      Ectopic endometrial establishment and growth are therefore likely to be
      suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2
      inhibition would reduce the size and number of ectopic human endometrial lesions
      in a nude mouse model of endometriosis. METHODS: The selective COX-2 inhibitor,
      nimesulide, was administered to estrogen-supplemented nude mice implanted with
      human endometrial tissue. Ten days after implantation, the number and size of
      ectopic endometrial lesions were evaluated and compared with lesions from a
      control group. Immunohistochemical assessment of vascular development and
      macrophage and myofibroblast infiltration in control and treated lesions was
      performed. RESULTS: There was no difference in the number or size of ectopic
      endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did
      not induce a visually identifiable difference in blood vessel development or
      macrophage or myofibroblast infiltration in nude mouse explants. CONCLUSION: The
      hypothesized biological properties of COX-2 inhibition did not influence lesion
      number or size in the nude mouse model of endometriosis.

PMID- 15567878
TI  - Would legislation imposing single embryo transfer be a feasible way to reduce the
      rate of multiple pregnancies after IVF treatment?
AB  - Due to increased maternal and fetal risks, there is a strong opinion in favor of
      single embryo transfer (SET) in order to reduce the high multiple pregnancy rate
      after IVF. We have evaluated the effects on pregnancy rate and twinning of recent
      Swedish legislation on SET. The study comprised three embryo transfer (ET)
      periods: period I, autumn 2001-spring 2002 (n=609), with a double embryo transfer
      (DET) policy; period II, autumn 2002 (n=320), a transitional period; and period
      III, January-September 2003 (n=433), with a SET policy. During the three periods,
      the SET rates were 25.1, 55.5 and 72.7%, respectively (Kruskal-Wallis test
      P<0.0001). There was no difference in clinical pregnancy rates (33.3, 32.8 and
      37.4%, respectively) (P=0.4), but the twinning rate was significantly lower in
      the third period (6.2 versus 22.6% in period I and 16.3% in period II) (P<0.005).
      After introducing a SET policy, the expected decline of twinning was met at an
      unchanged clinical pregnancy rate. Thus, the SET legislation had no negative
      consequences for the couples. On the contrary, the lower rate of twinning is
      expected to reduce the severity and rate of pregnancy complications after IVF.
      Whether legislation or voluntary SET is the most feasible way to proceed, in
      order to reduce the multiple pregnancy rates after IVF, can be debated.

PMID- 15567879
TI  - Timing ovulation for intrauterine insemination with a GnRH antagonist.
AB  - BACKGROUND: We aimed to assess the efficacy of a GnRH antagonist in intrauterine
      insemination (IUI) cycles to increase number of mature ovulatory follicles and
      pregnancy rates. METHODS: Prospective randomized study. Women (18-38 years old)
      with primary/secondary infertility were included. Eighty-two patients were
      randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH +
      GnRH antagonist or rFSH alone. RESULTS: A non-significant increase in the total
      amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect
      to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm)
      was significantly higher in the GnRH antagonist group than in the control group
      (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly
      increased in the group of patients receiving the GnRH antagonist (38%) compared
      to the control group (14%). The only non-single pregnancy (triplets) occurred in
      the antagonist group. CONCLUSIONS: In this preliminary study, adding the GnRH
      antagonist to the COS protocol for IUI cycles significantly increased pregnancy
      rates. Nevertheless, these results may not be associated directly with the
      antagonist itself but with the fact that more mature ovulatory follicles are
      present by the day of the hCG. Finally, the risk for multiple gestations needs to
      be carefully evaluated.

PMID- 15567880
TI  - Dose-finding study of daily GnRH antagonist for the prevention of premature LH
      surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical
      pregnancy.
AB  - BACKGROUND: An optimal range of LH concentrations for achieving pregnancy has not
      been established. The aim of this study was to investigate the effect of various
      LH levels induced by different GnRH antagonist doses on IVF outcome. METHODS:
      This was a prospective, single centre study including 144 IVF patients,
      stimulated with recombinant FSH from cycle day 2, and co-treated with daily GnRH
      antagonist (antide/Iturelix) (2 mg/2 ml, 1 mg/ml, 0.5 mg/ml, 0.5 mg/0.5 ml or
      0.25 mg/ml) from cycle day 7 onwards. Serum samples were taken three times daily.
      RESULTS: Clinical pregnancies were only observed within a particular range of
      change in LH levels. The upper and lower thresholds for the mean LH area under
      the curve (AUC), adjusted for the baseline LH level before the antagonist was
      started (LH AUC(-S6); S6=stimulation day 6) were -2.2 and 12.4 (IU/l)
      respectively (a negative value=below baseline levels). There were no clinical
      pregnancies outside these threshold values. Similar results were found for
      progesterone, the threshold levels of progesterone AUC(-S6) were 3.98 and -1.21
      ng/ml. Moreover, there were no pregnancies with progesterone levels >0.26
      ng/ml/follicle on the day of hCG. CONCLUSIONS: Excessive or insufficient
      suppression of LH and progesterone levels during GnRH antagonist administration
      and high progesterone/follicle on hCG day seems to be associated with impaired
      clinical pregnancy rates.

PMID- 15567881
TI  - Assisted reproductive technologies and the risk of birth defects--a systematic
      review.
AB  - BACKGROUND: The risk of birth defects in infants born following assisted
      reproductive technology (ART) treatment is a controversial question. Most
      publications examining the prevalence of birth defects in ICSI and IVF infants
      compared to spontaneously conceived infants have serious methodological
      limitations; despite this, most researchers have concluded that there is no
      increased risk. METHODS: We carried out a systematic review to identify all
      papers published by March 2003 with data relating to the prevalence of birth
      defects in infants conceived following IVF and/or ICSI compared with
      spontaneously conceived infants. Independent expert reviewers used criteria
      defined a priori to determine whether studies were suitable for inclusion in a
      meta-analysis. Fixed effects meta-analysis was performed for all studies and
      reviewer-selected studies. RESULTS: Twenty-five studies were identified for
      review. Two-thirds of these showed a 25% or greater increased risk of birth
      defects in ART infants. The results of meta-analyses of the seven reviewer
      selected studies and of all 25 studies suggest a statistically significant 30-40%
      increased risk of birth defects associated with ART. CONCLUSIONS: Pooled results
      from all suitable published studies suggest that children born following ART are
      at increased risk of birth defects compared with spontaneous conceptions. This
      information should be made available to couples seeking ART treatment.

PMID- 15567882
TI  - A randomized trial to compare 24 h versus 12 h double dose regimen of
      levonorgestrel for emergency contraception.
AB  - BACKGROUND: Levonorgestrel (0.75 mg given for two doses 12 h apart) has been
      proven to be an effective regimen for emergency contraception when the first dose
      is given within 72 h of unprotected coitus. However, the dosing interval is
      inconvenient for those taking the first dose in the afternoon. We conducted a
      randomized study to evaluate two levonorgestrel dosing regimens for emergency
      contraception. Two doses of levonorgestrel 0.75 mg were administered with the
      first dose given up to 120 h after unprotected intercourse. The second dose was
      given 12 h later in the first regimen and 24 h later in the second regimen.
      METHODS: We conducted a double-blind, randomized trial between 1997 and 2003 at
      five centres in China. A total of 2071 women requesting emergency contraception
      within 120 h of unprotected intercourse were recruited. They were randomized to
      receive two doses of 0.75 mg of levonorgestrel, given either 24 h apart or 12 h
      apart. RESULTS: Outcome was unknown for 53 women (24 in the 24 h group and 29 in
      the 12 h group). Among the remaining 2018 women, the crude pregnancy rate was
      1.9% in the 24 h group [95% confidence interval (CI) 1.17-2.94] and 2.0% in the
      12 h group (95% CI 1.19-2.99). The proportion of pregnancies prevented was
      estimated to be 72% in the 24 h group and 75% in the 12 h group. Side-effects
      were mild in both groups. The efficacy of the 12 h regimen declined significantly
      when there were further acts of intercourse after treatment (5.0 versus 1.0%,
      P<0.01). This was not observed in the 24 h group. CONCLUSIONS: Two doses of 0.75
      mg levonorgestrel given either 24 or 12 h apart are effective for emergency
      contraception up to 120 h after unprotected intercourse. Further research to
      investigative more effective methods of emergency contraception is warranted.

PMID- 15567883
TI  - Minimizing embryo expulsion after embryo transfer: a randomized controlled study.
AB  - BACKGROUND: The aim of this work was to modify the embryo transfer technique to
      prevent expulsion of the embryos by exerting gentle mechanical pressure on the
      cervix using the vaginal speculum. METHODS: A total of 639 infertile patients
      undergoing ICSI were prospectively randomized into two groups using sealed dark
      envelopes. In the study group (n=325) the screw of the vaginal speculum was
      loosened in order to exert a gentle pressure on the portiovaginalis of the cervix
      before ejecting the embryos, and was maintained for 7 min afterwards. In the
      control group (n=314) no pressure was applied on the cervix during embryo
      transfer and the vaginal speculum was removed after transferring the embryos.
      RESULTS: The clinical pregnancy rate was significantly higher in the study group
      than in the control group [207/325 (67%) versus 150/314 (47.8%); odds ratio (OR)
      1.39; 95% confidence interval (CI) 1.11-1.74]. The implantation rate was also
      significantly higher in the study group [304/913 (33.3%) versus 198/920 (21.5%);
      OR 1.54; 95% CI 1.26-1.89]. CONCLUSIONS: Applying gentle mechanical pressure on
      the portiovaginalis of the cervix using the vaginal speculum during and after
      transferring the embryos significantly improved clinical pregnancy and
      implantation rates.

PMID- 15567884
TI  - Persistent organochlorines, sedentary occupation, obesity and human male
      subfertility.
AB  - BACKGROUND: Studies have suggested that the quality of human semen has been
      declining over recent decades, presumably because of lifestyle or environmental
      factors. METHODS: Polychlorinated biphenyls and organochlorine pesticides were
      analysed in the plasma of 25 men with poor semen quality, 20 men with normal
      semen quality and idiopathic subfertility and 27 men with normal semen quality
      and female factor subfertility. Samples of seminal fluid were also analysed to
      assess the relationship between the levels in blood and semen. RESULTS: The
      results indicate no difference in the levels of organochlorines between the
      groups. The levels of organochlorines in seminal fluid were proportional to the
      levels in plasma, but approximately 40 times lower. Men with poor semen quality
      were three times more likely to be obese than men with normal semen quality.
      There was also a significant negative correlation between semen quality
      parameters and body mass index among men with normal semen quality. The
      prevalence of sedentary work was lowest among men with the best semen quality.
      CONCLUSIONS: Poor semen quality was found to be associated with sedentary work
      and obesity but not with plasma levels of persistent organochlorines. More
      research is needed to assess whether sedentary lifestyle and obesity are causal
      factors in the decline of semen quality.

PMID- 15567885
TI  - Detailed FISH analysis of day 5 human embryos reveals the mechanisms leading to
      mosaic aneuploidy.
AB  - BACKGROUND: Fluorescence in situ hybridization (FISH) analysis has shown that
      human embryos display a high level of chromosomal mosaicism at all
      preimplantation stages. The aim of this study was to investigate the mechanisms
      involved by the use of two probes for each of three autosomes at different loci
      and to determine the true level of aneuploid mosaicism by excluding FISH
      artefacts. METHODS: Embryos were cultured in two different types of medium: group
      I were cultured in standard cleavage medium for up to day 5 and group II were
      cultured from day 3 to day 5 in blastocyst medium. Three rounds of FISH were
      performed. In round 1, the probes used were 1pTel, 11qTel and 18CEP; in round 2,
      the probes used were 1satII/III, 11CEP and 18qTel; in round 3, the probes used
      were 18CEP, XCEP and YCEP. RESULTS: A total of 21 embryos were analysed in each
      group. The FISH results revealed one uniformly diploid and 20 mosaic embryos for
      group I, and two uniformly diploid and 19 mosaic embryos for group II. The
      predominant type of mosaicism was diploid/aneuploid. The use of two different
      probes per autosome was able to distinguish FISH artefacts affecting 5% of nuclei
      from true single cell anomalies. CONCLUSIONS: Post-zygotic chromosome loss was
      the most common mechanism leading to aneuploidy mosaicism for both groups,
      followed by chromosome gain, with fewer examples of mitotic non-disjunction.

PMID- 15567886
TI  - Dynamics of group formation in collective motion of organisms.
AB  - A mathematical description of the collective motion of organisms using a density
      velocity model is presented. This model consists of a system of nonlinear
      parabolic equations, a forced Burgers equation for velocity and a diffusion
      convection equation for density. The motion is mainly due to forces resulting
      from the differences between local density levels and a prescribed density level.
      The existence of a global attractor for a 1D density-velocity model is proved by
      asymptotic analysis to demonstrate different patterns in the attractors for
      density. The theoretical results are supplemented with numerical results. These
      patterns correspond to movements of collective organized groups of organisms such
      as fish schools and bird flocks.

PMID- 15567887
TI  - Platelet-wall interactions in continuum models of platelet thrombosis:
      formulation and numerical solution.
AB  - A model is developed to describe the formation of platelet thrombi in coronary
      artery-sized blood vessels. It involves interactions among a viscous,
      incompressible fluid; populations of non-activated and activated platelets;
      activating chemicals; and the vessel walls. Adhesion of platelets to the injured
      wall and cohesion between activated platelets is modelled using distributions of
      elastic links which generate stresses that can influence the fluid motion. The
      first version of the model presented involves two spatial scales: the microscale
      of the platelets and the macroscale of the vessel. A closure approximation is
      introduced that allows essential microscale behaviour to be computed while
      eliminating the necessity to explicitly track events on this scale. Computational
      methods are presented that meet the diverse challenges posed by the coupled
      nonlinear partial differential equations of the model and by the complex geometry
      of the constricted vessels in which the thrombosis simulations are carried out.
      Simulation results demonstrate that the model can produce thrombi that grow to
      occlude the vessel, that shear-stress exerted by the fluid on the thrombi can
      modify their subsequent growth and cause remodelling of their shape through small
      scale local changes or large-scale structural breakup.

PMID- 15567888
TI  - Simulating realistic zero loop pedigrees using a bipartite Prufer code and
      graphical modelling.
AB  - Graph algorithms previously developed by the authors are adapted to simulate
      pedigrees similar to those used in genetic linkage studies which associate
      disease phenotypes with specific genomic locations. Pedigrees are chosen
      uniformly at random from the set of those with specified numbers of individuals
      and matings and which contain no loops. Summary statistics from pedigrees
      generated in this way can be used to check real pedigrees for anomalies due to
      biased sampling or phenotypic effects on the pedigree structure.

PMID- 15567889
TI  - A model of in-vivo hydrocephalus shunt dynamics for blockage and performance
      diagnostics.
AB  - The accumulation of excess cerebrospinal fluid in the ventricles of the brain
      results in hydrocephalus, a condition that is fatal if left untreated. The usual
      remedy is to insert a shunt into the ventricles of the brain, which drains excess
      fluid away, moderated by a pressure dependent valve. It is important that the
      system functions properly so that a reasonable intracranial pressure is
      maintained. Unfortunately, pressure measurements in the ventricles are highly
      invasive, while pressure measurements in the shunt outside the skull may not
      detect any blockage in the catheter inside. Here we develop a model primarily
      aimed at detecting in vivo a blockage and other shunt malfunction using non
      invasive measurements, so that shunt valves can be adjusted accordingly. The
      system offers a clear insight into how currently available clinical measurements
      may be utilized. We then extend this to investigate the phenomenon of 'chatter'
      (rapid opening and closing) and other mechanisms including intracranial pressure
      pulsatility. Although simple, the model offers a clear indication of what is
      required for successful regulation of both intracranial pressure and shunt flow.

PMID- 15567890
TI  - Estimating the number of prions in yeast cells.
AB  - Certain yeast cells contain proteins that behave like the mammalian prion PrP and
      are called yeast prions. The yeast prion protein Sup35p can exist in one of two
      stable forms, giving rise to phenotypes [PSI(+)] and [psi(-)]. If the chemical
      guanidine hydrochloride (GdnHCl) is added to a culture of growing [PSI(+)] cells,
      the proportion of [PSI(+)] cells decreases over time. This process is called
      curing and is due to a failure to propagate the prion form of Sup35p. We describe
      how curing can be modelled, and improve upon previous models for the underlying
      processes of cell division and prion segregation; the new model allows for
      asymmetric cell division and unequal prion segregation. We conclude by outlining
      plans for future experimentation and modelling.

PMID- 15567892
TI  - A global approach combining proteome analysis and phenotypic screening with RNA
      interference yields novel apoptosis regulators.
AB  - Global approaches like proteome or transcriptome analyses have been performed
      extensively to identify candidate genes or proteins involved in biological and
      pathological processes. Here we describe the identification of proteins
      implicated in the regulation of apoptosis using proteome analysis and the
      functional validation of targets by RNA interference. A high-throughput platform
      for the validation of synthetic small interfering RNAs (siRNAs) by quantitative
      real-time PCR was established. Genes of the identified factors were silenced by
      automated siRNA transfection, and their role in apoptotic signaling was
      investigated. Using this strategy, nine new modulators of apoptosis were
      identified. A subsequent detailed study demonstrated that hepatoma-derived growth
      factor (HDGF) is required for TNFalpha-induced release of pro-apoptotic factors
      from mitochondria. The strategy described here may be used for hypothesis-free,
      global gene function analysis.

PMID- 15567893
TI  - Influence of red blood cell concentration on the initiation time of blood
      coagulation: risk of thrombus formation by hemoconcentration.
AB  - Influence of the change of red blood cell (RBC) concentration on the initiation
      time of blood coagulation was investigated with a damped oscillation rheometer.
      The blood samples from 40 volunteers were examined. After centrifuging some
      portion of each blood sample, an appropriate volume was taken from the lower RBC
      layer to add it to the autologous blood, making an artificially concentrated
      blood. Initiation time of coagulation of each sample from 20 males and 20 non
      pregnant females was shortened according to the increase of the RBC
      concentration, producing a significant difference at the boundary of
      5.0x10(6)/mm3 (p<0.01). The results suggest that RBC concentration may play an
      important role in accelerating the initial coagulation reaction of blood and that
      hemoconcentration could be a risk factor for thrombosis even within the normal
      range, especially beyond the boundary of 5.0x10(6)/mm3 of RBCs.

PMID- 15567894
TI  - The effect of simvastatin therapy on hemorheological profile in coronary heart
      desease (CHD) patients.
AB  - This study was designed to examine changes of hemorheological parameters in
      patients with CHD and hypercholesterolaemia (wide range of plasma total
      cholesterol level from 5.6 to 9.8 mmol.l-1) subjected to lipid lowering therapy
      with statins (simvastatin, 10.0-20.0 mg/day, dosage was dependent on an initial
      level of total cholesterol). Twenty female subjects were enrolled in this
      research program. Both prior to and following drug treatment for eight weeks,
      hemorheological measurements included plasma viscosity, high and low shear whole
      blood viscosity, hematocrit, RBC aggregation and rigidity. Treatment with
      simvastatin significantly (p<0.05) reduced total cholesterol, total triglycerides
      and low-density lipoprotein cholesterol (LDL-C). However, the hemorheological
      effects of lipid lowering therapy differed markedly between macro- and
      microrheological groups of parameters: plasma and whole blood viscosity were not
      significantly changed whereas RBC aggregation and its rigidity were decreased
      significantly after statin treatment. These results thus suggest that the
      rheologic effect of lipid lowering therapy concerned mainly the microrheological
      parameters: red cell aggregation and deformability.

PMID- 15567895
TI  - Influence of P. vivax malaria on erythrocyte aggregation and deformability.
AB  - Malaria due to Plasmodium vivax affects blood flow in cardiovascular system. The
      present work is aimed to determine the variability of erythrocyte deformability
      and aggregation in malaria patients in comparison with that of normal subjects.
      Blood samples of malaria patients (n=16), selected based on occurrence of
      parasitaemia, are categorized into low (LP), medium (MP) and high parasitaemia
      (HP), which represent increasing levels of the disease severity. For measurement
      of aggregation and deformability, by laser aggregometer and optical
      hemorheometer, the erythrocyte suspensions are prepared in plasma and
      physiological saline at hematocrit 5%. The results show that the erythrocyte
      deformability is significantly reduced (p<0.001) with the increasing level of
      parasitaemia. Despite this decrease in deformability, the aggregation parameters
      are significantly increased, indicating the occurrence of hyper-aggregation,
      particularly in MP and HP, due to involvement of various factors. These changes
      may partly be contributing in the observed changes in blood flow in the
      microcirculation.

PMID- 15567896
TI  - Ganoderma lucidum suppresses endothelial cell cytotoxicity and proteinuria in
      persistent proteinuric focal segmental glomerulosclerosis (FSGS) nephrosis.
AB  - A persistent proteinuria is commonly observed in nephrotic patient with focal
      segmental glomerulosclerosis (FSGS) under treatment with prednisolone+/
      cyclophosphamide or with vasodilators (ACEI+AII receptor antagonist, calcium
      channel blocker and antiplatelet agent). Fourteen such patients with persistent
      proteinuria were subject to be treated with Ganoderma lucidum. Initial study
      revealed an enhanced endothelial cell cytotoxicity induced by patient's serum,
      and an altered immunocirculatory balance with predominant proinflammatory
      cytokine TNF alpha activity in the presence of defective anti-inflammatory
      cytokine interleukin-10. Treatment with Ganoderma lucidum suppressed endothelial
      cell cytotoxicity, restored immunocirculatory balance and successfully suppressed
      proteinuria in all of these 14 patients.

PMID- 15567897
TI  - Influence of hyperglycemia on aggregation, deformability and shape parameters of
      erythrocytes.
AB  - The hemorheological and morphological changes in blood samples of diabetic
      patients, with varying levels of hyperglycemia but normal cholesterol
      concentration, are determined and are compared with healthy subjects. The shape
      analysis is carried out by shape descriptors based on projected area, perimeter
      and form factor, as measured by processing of images of erythrocytes. The
      aggregation and deformability of erythrocytes are measured by sequential
      variation of the transmitted laser light after passing through the erythrocytes
      suspension in plasma and passage of erythrocytes suspension in physiological
      saline through cellulose membrane, respectively. The results show that with the
      increase of glucose concentration the erythrocytes aggregation is enhanced and
      deformability is reduced in diabetic patients compared to that of healthy
      subjects. The shape parameters, which quantify the changes in erythrocytes in
      diabetes, show significant deviation from the shape of normal cells. A
      significant increase in the perimeter to area ratio and form factor in
      hyperglycemia also corresponds to highly significant increase in filtration time
      (decrease in deformability).

PMID- 15567898
TI  - Peripheral vasculopathy in patients with systemic sclerosis: difference in
      limited and diffuse subset of disease.
AB  - OBJECTIVE: To examine the difference in clinical signs of peripheral vasculopathy
      in patients (pts) with limited (lcSSc) and diffuse cutaneus systemic sclerosis
      (dcSSc). PATIENTS AND METHODS: Ninety one patients with systemic sclerosis (39
      with lcSSc and 52 with dcSSc) have been assessed for the presence of clinical
      signs of vascular injury: Raynaud's phenomenon, severity of capillary damage on
      capillaroscopy, presence or absence of finger-tip ulcers or pitting scars,
      presence of telangiectasias and radiographic signs of finger-tip osteolysis.
      Statistical significance of difference in clinical manifestations of peripheral
      vasculopathy in pts with lcSSc and dcSSc was assessed using the Mann-Whitney and
      X2-test. RESULTS: Duration of Raynaud's phenomenon before manifestation of skin
      or internal organ damage, was significantly longer (z=-2.54, p=0.004) in patients
      with lcSSc (5.4 years) than in patients with dcSSc (1.9 years). Using the
      technique of nailfold capillaroscopy, we found normal capillaries or non-specific
      capillary change in 10.2% pts with lcSSc and only in 2.0% pts with dcSSc.
      Enlarged capillaries without significant loss of capillaries were found in 38.5%
      pts with lcSSc, and 11.5% pts with dcSSc (p=0.05). But severe capillary damage,
      with significant loss of capillaries, was noticed more frequently in pts with
      dcSSc (dcSSc/lcSSc: 86.5%/51.3%, p=0.002). Pitting scars or digital ulcers were
      found in 46.2% pts with lcSSc and 67.3% pts with dcSSc (p=0.04). We did not
      notice significant difference in frequency of finger-tip osteolysis (lcSSc/dcSSc:
      23.1%/21.2%, p>0.05) and telangiectasias (lcSSc/dcSSc: 46.2%/53.8%, p>0.05).
      CONCLUSION: Severe capillary damage and digital ulcers are more common in
      patients with diffuse cutaneus systemic sclerosis, but finger-tip osteolysis and
      telangiectasias are equally frequent in both form of disease.

PMID- 15567899
TI  - Endothelial injury and altered hemodynamics in thalassemia.
AB  - Increased activated circulating endothelial cells, enhanced von Willebrand factor
      (vWF:Ag) and adhesion molecules (sVCAM-1) are observed in patients with beta
      thalassemia/hemoglobin E. Such evidences of endothelial cell injury are
      associated with altered intrarenal hemodynamics with a significant reduction in
      renal plasma flow. Altered renal functions (namely depleted creatinine clearance)
      and abnormal tubular function test, which is reflected by abnormally increased
      fractional excretion of magnesium (FE Mg), are also delineated. The increased FE
      Mg implies tubulointerstitial injury which may relate to the microvascular
      endothelial injury and chronic ischemia.

PMID- 15567900
TI  - Red blood cell deformability, aggregability and cytosolic calcium concentration
      in normal tension glaucoma.
AB  - AIM: The aim of the study was to determine the role of some erythrocyte patterns
      (Red Blood Cell deformability, aggregability, cytosolic calcium concentration) in
      normal tension glaucoma (NTG), compared with primary open angle glaucoma (POAG)
      and normal subjects. MATERIAL AND METHODS: Ninety patients entered the study,
      divided in three groups: age and sex-matched, otherwise normal subjects (30
      patients), POAG (30 patients) and NTG patients (30 patients). Hemorheological
      parameters (elongation index [EI] and aggregability half time [At1/2] were
      detected using a laser diffractometer system (Laser-assisted Optical Rotational
      Cell Analyzer [LORCA]). Cytosolic calcium levels were measured using
      spectrofluorimetry. RESULTS: No significant difference in systemic variables and
      refractive error was found. Mean hematocrit level, cell volume, plasma protein
      level and coagulation factors did not show any statistical difference among
      groups and resulted to be in the range of normality. A significant decrease in EI
      measurements was demonstrated in the NTG group (p<0.001) only. Similarly, A-t1/2
      measurements were significantly smaller in the NTG group than in the other groups
      (p<0.001). Cytosolic calcium levels were significantly higher in the NTG group
      than in the other groups (p<0.001) and they were correlated to the elongation
      index for each group and overall (r=-0.756, p<0.001). CONCLUSIONS: A significant
      decrease of erythrocyte deformability and increase in aggregability was found in
      NTG patients. These alterations seem to be inversely related to the
      intracytosolic calcium levels and they were not found in POAG patients and
      controls. Those results may contribute to understand the pathogenesis of normal
      tension glaucoma, suggesting a possible role played by red blood cells.

PMID- 15567901
TI  - Spectral analysis of skin laser Doppler blood perfusion signal during cutaneous
      hyperemia in response to acetylcholine iontophoresis and ischemia in normal
      subjects.
AB  - Spectral analysis of skin laser Doppler (LD) signal was performed using Fourier
      transformation in twelve healthy subjects in order to compare post-ischemic
      hyperemia and acetylcholine (ACh) iontophoresis tests for the exploration of
      cutaneous microcirculatory endothelial function. Within the frequency range
      studied of 0.009-1.6 Hz, five different frequency intervals were considered,
      arising from local (endothelial and myogenic) and central (neural, respiratory
      and cardiac) regulatory mechanisms. The power density (PD) for each of the five
      frequency intervals considered was measured in perfusion units (PU)/Hz, in each
      subject, before and in response to ischemia and to ACh iontophoresis, using a
      dedicated software. The relative contribution of each frequency interval was
      calculated as per cent rate between each PD and the sum of the PD of the five
      frequency interval considered. PD of LD signals in response to ischemia and Ach
      iontophoresis significantly increased for all the five frequency intervals
      considered. A significant increase (from 25.0+/-6.3 to 48.3+/-17.8; p<0.01) in
      the relative contribution of 0.009-0.02 frequency interval, referred to
      endothelium activity, was observed only in response to ACh iontophoresis. No
      significant increase in the relative power contribution was observed in response
      to ischemia for any of the five frequency intervals considered. These data
      suggest that ACh iontophoresis test is more adequate than post-ischemic hyperemia
      test in exploring the skin microcirculatory endothelial function in normal
      subjects.

PMID- 15567902
TI  - Opposite effects of in vitro lactate on erythrocyte deformability in athletes and
      untrained subjects.
AB  - Exercise transiently increases blood viscosity: however data on red cell
      deformability in this process remain inconsistent, since studies report either
      impairment (proportional to blood lactate accumulation), a lack of effect, or
      even in some cases an improvement. To test whether these inconsistencies may be
      due to physiological differences among populations studied, we compared the
      effects of in vitro lactate (2 mM, 4 mM and 10 mM) on erythrocyte rigidity in
      venous blood drawn at rest in 10 untrained vs 10 aerobically-trained subjects.
      After adjustment of osmolality and pH and incubation at 37 degrees C during 2
      minutes, viscometric measurements were performed at 1000 s-1 with the MT90
      (falling ball) viscometer and Dintenfass's 'Tk' was calculated. While at baseline
      there was no significant difference in Tk between the two groups, it decreased in
      the aerobically-trained subjects between 2 and 10 mM lactate concentrations
      (p<0.05) and increased in the untrained group between 2 and 4 mM (p<0.05). Thus,
      it seems that endurance training influences erythrocyte response to lactate.
      Lactate impaired erythrocyte deformability in untrained subjects but it
      (unexpectedly) improved it in trained subjects. This difference may be due to
      training-induced adaptations in erythrocyte metabolism, possibly including
      transmembrane transfer via monocarboxylate transporters.

PMID- 15567903
TI  - Association of serum antioxidants and risk of coronary heart disease in South
      Indian population.
AB  - BACKGROUND AND AIM: Higher prevalence of coronary heart disease (CHD) has been
      reported in south Indian population, which cannot be accounted for by the
      traditional risk factors like hyperlipidemia. Identification of new risk factors
      may help in treatment and prevention of CHD in this part of the world. In an
      attempt to investigate the causes of increased incidence of CHD in this part of
      the world, we intended to look for oxidative stress in our patients as a possible
      risk factor. As an initial step in this perspective, a case- control study was
      conducted to find out the serum antioxidant levels and their association with CHD
      in south Indian population. SETTINGS AND DESIGN: A tertiary care hospital; Case-
      control study. MATERIALS AND METHODS: One hundred thirty nine angiographically
      proven CHD patients (aged 29-75 years) were studied against 59 population based
      healthy controls (aged 29-72 years) free of CHD. Fasting serum cholesterol,
      triglycerides, HDL cholesterol, erythrocyte and plasma glutathione peroxidase and
      superoxide dismutase were estimated on automated clinical chemistry analyzer. LDL
      cholesterol and VLDL cholesterol were calculated. Vitamins A and E were estimated
      using high performance liquid chromatography (HPLC). STATISTICAL ANALYSIS:
      Unpaired t test was used to compare means. Binary logistic regression was done to
      find out the association between dependent and independent variables. RESULTS:
      Significantly higher levels of Total Cholesterol/HDL cholesterol and LDL
      cholesterol/HDL cholesterol ratio and lower HDL cholesterol levels were observed
      in patients when compared to controls. No significant difference of plasma and
      erythrocyte glutathione peroxidase and superoxide dismutase activity was observed
      between patients and controls. Significantly lower levels of vitamin E in
      patients than in controls was observed (P<0.001). Serum vitamin E was inversely
      associated with coronary heart disease even after controlling for age and other
      coronary risk factors (Odds ratio 0.898, 95% CI 0.826-0.976 P=0.01). CONCLUSIONS:
      The results of present study suggest that deficiency of vitamin E may be an
      independent risk factor of CHD. This study brings out the need for long- term
      monitoring of vitamin E supplementation as a preventive measure for CHD in the
      population studied.

PMID- 15567904
TI  - Immunogenicity and safety of hepatitis B vaccine (Shanvac-B) using a novel pre
      filled single use injection device Uniject in Indian subjects.
AB  - BACKGROUND: Hepatitis B is a major public health problem, which has now been
      controlled to some extent by vaccination especially with the recombinant
      hepatitis B vaccine, which has been proven to be safe and efficacious since its
      introduction in the 1990s. But problems of unsafe injection practices still
      persist. Now newer delivery devices like uniject are available for making
      vaccination very safe. OBJECTIVE: To evaluate the immunogenicity and safety of
      the Hepatitis-B (Shanvac-B) vaccine in Uniject pre-filled device administered to
      healthy adults and infants at 0, 1, 2 months schedule. METHODS: A total of 122
      healthy subjects (62 adults and 60 infants) were administered three doses of the
      recombinant Hepatitis-B vaccine using Uniject pre-filled device. Blood samples
      for antibody titer estimation were taken before vaccination and 4-6 weeks after
      third dose. Subjects, parents or guardians were given diary cards to record any
      adverse reactions. RESULTS: Protective immune responses to the vaccine were seen
      in 96.4% of adults and 100% of infants who completed the study. The Geometric
      Mean Titers (GMT) in adults and infants were 518.5 and 385.41 mIU/ml
      respectively. Mild fever, itching, and swelling at injection site were the most
      common side effects observed. CONCLUSION: The safety and immunogenicity of the
      Hepatitis B Vaccine in the novel pre-filled device Uniject was effectively
      demonstrated in the present study.

PMID- 15567905
TI  - Induced abortion and concurrent adoption of contraception in the rural areas of
      India (an ICMR task force study).
AB  - BACKGROUND: Despite a liberal Medical Termination of Pregnancy (MTP) act and
      awareness of family planning, maternal mortality attributable to induced abortion
      is high. AIMS: Assess attitude, behavior, practices and utilization of services
      by rural women for induced abortion and concurrent acceptance of contraception.
      SETTINGS AND DESIGN: Cross sectional survey of eligible married women in 13
      states in India over one year. MATERIAL AND METHODS: A total of 1851 women who
      had an induced abortion during the previous 3 years were interviewed. STATISTICAL
      ANALYSIS USED: Includes proportions, rates and chi-square test. RESULTS: The main
      reason for seeking abortion was "don't need any more children" (42%), and in 12.4
      per cent they specifically mentioned that they "don't need any more daughters".
      Around 46% of women accessed abortion services from private clinics as compared
      to government hospital (37.1%) and Primary Health Centre/Community Health Centre
      (14.0%). The decision to terminate the pregnancy and place of abortion was made
      by the husband in 42.8% and 52.5% respectively. Regret for abortion was expressed
      by 29.6% of the women. However, only 7.2% said they would not advice others for
      induced abortion. Nearly one half of the women undergoing abortion accepted a
      family planning method concurrently; of these Intra Uterine Device/oral
      contraceptives and a permanent method was adopted by 37.2% and 49.1%
      respectively. Acceptance of vasectomy by male partner was found to be low (1.3%).
      "Husband objected" (32.3%) was the main reason for not accepting post abortal
      contraception. Majority of the acceptors said they would recommend to others the
      same place where they had undergone abortion, thus indicating their satisfaction
      with the source and services received. CONCLUSIONS: Counselling for post-abortal
      contraceptive should be provided to the couple so that they can make an informed
      choice.

PMID- 15567906
TI  - Antiphospholipid syndrome in childhood onset systemic lupus erythematosus.

PMID- 15567907
TI  - Smoking pattern among the workers engaged in textile industries of desert
      districts of Rajasthan.

PMID- 15567908
TI  - Thrombophilia markers in acute myocardial infarction of the young.

PMID- 15567909
TI  - Hemoglobinopathies and other congenital hemolytic anemia.

PMID- 15567910
TI  - [Online-conference using JGN.].
AB  - Telemedicine and online conference systems have some benefits so that equalizing
      medical level, improving efficiency of medical care and improving service for
      patients. It is possible to give advice and to support its medical projects
      stationed in other facility and to provide the same quality treatments for
      patients. In this paper, we set up an experimental network system to
      teleconference using JGN (Japan Gigabit Network) and tried to discussion
      alternatively for case study between Kanazawa university and Fukui red cross
      hospital, 70 km away. The JGN used in this study is an ultra-high-speed network
      for the purpose of research and development. Kanazawa university, and Fukui red
      cross hospital are connected by a 10 Mbps communication link of the JGN. We tried
      online conference on the experimental network using video chat system. In result,
      using video chat system, the average transmission rate of MRI images (256 X
      256pixel, 16bit) is 0.2 s/frame.

PMID- 15567911
TI  - [Relationship between line spread function (LSF), or slice sensitivity profile
      (SSP), and point spread function (PSF) in CT image system.].
AB  - In the CT image system, we revealed the relationship between line spread function
      (LSF), or slice sensitivity profile (SSP), and point spread function (PSF). In
      the system, the following equation has been reported; I(x,y) = O(x,y) **
      PSF(x,y), in which I(x,y) and O(x,y) are CT image and object function,
      respectively, and ** is 2-dimensional convolution. In the same way, the following
      3-dimensional expression applies; I'(x,y,z) = O'(x,y,z) *** PSF'(x,y,z), in which
      z-axis is the direction perpendicular to the x/y-scan plane. We defined that the
      CT image system was separable, when the above two equations could be transformed
      into following equations; I(x,y) = [O(x,y) * LSF(x)(x) ] * LSF(y)(y) and I'
      (x,y,z) = [ O'(x,y,z) * SSP(z) ] ** PSF(x,y), respectively, in which LSF(x)(x)
      and LSF(y)(y) are LSFs in x- and y-direction, respectively. Previous reports for
      the LSF and SSP are considered to assume the separable-system. Under the
      condition of separable-system, we derived following equations; PSF(x,y)=LSF(x)(x)
      LSF(y)(y) and PSF' (x,y,z) = PSF(x,y) SSP(z). They were validated by the computer
      simulations. When the study based on 1-dimensional functions of LSF and SSP are
      expanded to that based on 2- or 3-dimensional functions of PSF, derived equations
      must be required.

PMID- 15567913
TI  - Innate immunity contributes to cochlear adaptive immune responses.
AB  - Inner ear immune responses mediated by antigen-specific processes are thought to
      contribute to hearing loss in humans. Systemic activation of innate immunity
      contributes to immune responses in the central nervous system. We hypothesized
      that activation of innate immunity can prime the inner ear for adaptive immune
      responses and exacerbate disease. Mice were systemically immunized with antigen.
      Three weeks after initial antigen exposure, the antigen was injected
      intrathecally coincident with systemic injection of lipopolysaccharide (LPS), an
      activator of innate immunity. Responses were measured by quantifying the
      leukocyte infiltrate and cochlear IL-1beta expression. LPS stimulation markedly
      amplified the adaptive immune response to exogenous antigen in the inner ear.
      These data indicate that the cochlea is activated by systemic events that
      stimulate innate immunity and when antigen is present in the inner ear, a robust
      cochlear adaptive response is generated. If true in humans, this implies that
      priming may be an important component in the development of immune-mediated
      hearing loss.

PMID- 15567914
TI  - Loss of peripheral right-ear advantage in age-related hearing loss.
AB  - In young adults with normal hearing, the right ear is more sensitive than the
      left to simple sounds (peripheral right-ear advantage) and to processing complex
      sounds such as speech (central right-ear advantage). In the present
      investigation, the effects of hearing loss and aging on this auditory asymmetry
      were examined at both peripheral and central levels. Audiograms and transient
      evoked otoacoustic emission (TEOAE) and distortion product otoacoustic emission
      amplitudes were used to assess cochlear function. The contralateral suppression
      of TEOAEs was measured to assess the medial olivocochlear efferent system. The
      Hearing in Noise Test (HINT; binaural speech) was conducted to assess higher
      central auditory function. A group of aged subjects with normal hearing (flat
      audiograms) were compared to a group of aged subjects with sloping audiograms
      (presbycusis). At the cochlear (peripheral) level, the normal hearing group
      showed significantly higher otoacoustic emission amplitudes for the right ear
      compared to the left ear, which is consistent with the right-ear dominance
      normally seen in young adults. However, this finding was reversed in the
      presbycusic group that showed higher left-ear emission amplitudes. At the
      brainstem level, the amplitudes of TEOAE contralateral suppression were small and
      no significant difference was found between the right and left ears in both
      groups. On the contrary, HINT results showed a continuous dominance of the right
      ear (left hemisphere) in both groups, which was consistent with previous reports
      showing that the right hemisphere is more affected by age than the left
      hemisphere.

PMID- 15567915
TI  - Renal transplantation. Strategies to prevent organ rejection--the role of an
      inter-regional reference center.
AB  - This paper summarizes the role of the Inter-Regional Reference Center (RC) of the
      North Italy Transplant program (NITp), in coordinating a donor procurement and
      organ transplantation network, with a special focus on the strategies to minimize
      immunological risk and complications after transplantation. In the NITp, patients
      enrolled on the renal transplantation (RT) waiting list are typed for HLA
      A,B,DRB1 antigens with a genomic method. They are periodically screened for the
      presence of lymphocytotoxic antibodies in their serum by the RC and their
      suitability to receive the transplant is checked periodically. Cadaver kidney
      allocation is ruled by a computerized algorithm, named NITK3, established in
      1997, which aims at ensuring quality, equity, transparency and traceability
      during all the phases of the allocation decision-making process. NITK3 has been
      set up by the NITp Working Group on the basis of biological, medical and
      administrative criteria and it is periodically reviewed after the analysis of
      transplant results. In this paper, we show the results of a preliminary analysis
      of RTs performed from 1998 to 2002 in nine out of sixteen centers of the NITp
      area, which demonstrates the general quality of the NITp program in terms of
      patients and graft survival and the special attention to the patients at higher
      immunological risk.

PMID- 15567916
TI  - Kidney transplantation in the hyperimmunized patient.
AB  - Individuals who have developed anti-HLA class I and II antibodies are said to be
      immunized or sensitized. High levels of donor specific anti-HLA antibodies
      present at the time of transplantation frequently result in early allograft loss
      due to humoral rejection. Lower levels of donor specific anti-HLA antibodies
      (DSA) are also associated with poor outcome. Technological advances in tissue
      typing permit the detection of low levels of DSA not seen with standard
      cytotoxicity cross-match tests. These tests which previously were used to screen
      patients to avoid transplantation of donor-immunized patients are now being used
      to stratify patients based on their degree of donor alloreactivity. New protocols
      have been developed which permit successful transplantation despite the presence
      of DSA. These protocols utilize intravenous immunoglobulin infusions prior to
      transplantation, either alone or in combination with plasmapheresis to block or
      remove DSA. Using these protocols many persons previously considered essentially
      nontransplantable are now able to successfully receive transplants. Improved
      recognition of the clinicopathological characteristics of humoral rejection have
      allowed earlier diagnosis and treatment of antibody-mediated allograft injury and
      improved the outcome. Although these advances have improved the outlook for
      highly immunized kidney transplant candidates, more study is needed to delineate
      the optimal approach to transplantation in this population.

PMID- 15567917
TI  - Chronic induction. What's new in the pipeline.
AB  - Induction therapy with biological agents was introduced the in the 1970s and the
      rationale, concepts and approach have remained almost unchanged for 30 years.
      However, the novel biological agents being developed for induction therapy are
      being designed for chronic rather than short-term therapy with several
      objectives: reduce dependence on toxic and nephrotoxic agents, improve outcome
      and ultimately facilitate the emergence of tolerance. The biological agents
      include efalizumab, a humanized anti-CD11a (anti-LFA1), anti- CD154, anti-CD40, a
      number of agents targeting IL-15 and its receptor, and costimulation blockade
      with humanized antibodies to CD80/CD86 and the fusion receptor protein LEA29Y, a
      second generation CTLA4Ig. The past decade has witnessed an unprecedented number
      of small molecules/oral drugs that have been developed and approved for renal
      transplantation; the next decade, however, may witness the emergence of a new
      class of biological induction agents that may displace some of the currently used
      drugs.

PMID- 15567918
TI  - Steroid or calcineurin inhibitor-sparing immunosuppressive protocols.
AB  - Steroids have accompanied other immunosuppressants throughout the history of
      renal transplantation. However, its permanent use has been associated with a
      myriad of adverse effects, which especially increase the already high
      cardiovascular risk of renal transplant patients. Nevertheless, steroid-sparing
      strategies may increase the risk of acute and chronic rejection that may worsen
      the fate of transplant recipients. The advent of new immunosuppressants have
      renovated the interest on steroid-sparing protocols, and the results of the new
      trials suggest that these strategies may be safe enough in view of the low rates
      of acute rejection and stable renal function reported. On the other hand,
      calcineurin inhibitors (CNIs) have been considered the cornerstone of transplant
      immunosuppression though their nephrotoxicity has been one of the major clinical
      problems in the use of these immunosuppressants. The balance between preventing
      immunological allograft losses and the management of CNI-related nephrotoxicity
      is still an issue in renal transplantation. CNI reduction or elimination may
      increase the risk of acute and chronic rejection. Because of these concerns, in
      most instances CNI have been used at conventional doses in induction and
      maintenance therapy. As in the case of steroid-sparing strategies, the new
      therapeutic arsenal has provided a new impulse in CNI-sparing regimens, with an
      acceptable low rate of acute rejection, well-preserved renal function and without
      an apparent increased risk of chronic rejection, which may pave the way for a new
      era in immunosuppression.

PMID- 15567919
TI  - Steroid-free lymphocyte depletion protocols. The potential for partial tolerance?
AB  - Induction of tolerance has been a longstanding goal in transplantation. Recent
      preliminary studies using a steroid-free lymphocyte depletion strategy have been
      met with great excitement and an equal degree of skepticism. Current studies in
      this area suggest that immunosuppression can be reduced substantially but acute
      rejection develops at a rate approximately twice that of standard triple drug
      protocols. None of the lymphocyte-depleting protocols has resulted in full
      tolerance as evidenced by patients attaining a maintenance drug-free state.
      Workers in the field have suggested that a degree of tolerance is achieved and
      they have coined a growing number of terms to describe this state: prope
      tolerance, metastable tolerance, and partial tolerance. To date, patient follow
      up has been relatively short leaving many unanswered questions about graft
      survival, chronic allograft nephropathy, and the minimally effective maintenance
      immunosuppression. Despite these limitations, steroid-free lymphocyte depletion
      may offer an exciting new treatment paradigm.

PMID- 15567920
TI  - Chronic graft loss. Immunological and non-immunological factors.
AB  - AIMS: Late loss of kidney grafts is an ongoing problem in the field of
      transplantation. This is caused by immunological and non-immunological factors,
      the main immunological driver of rejection is the immune response against HLA
      molecules that differ between donor and recipient. METHODS: To measure the anti
      donor responses that a recipient can mount, we have been quantifying anti-donor T
      cell frequencies in recipients of renal transplants for several years. Anti-donor
      direct and indirect pathway frequencies have been measured in vitro in kidney and
      heart transplant patients by Limiting dilution analysis and other methods.
      Further, to elucidate the role of CD4+CD25+ regulatory T-cells, these cells have
      been depleted in ex vivo assays of cellular function. Antigen specific CD4+CD25+
      cell lines are being expanded in vitro with a view to using them in
      immunotherapeutic strategies. RESULTS: Frequencies of T-cells with direct pathway
      anti-donor specificity decline in most patients, while those with indirect anti
      donor specificity increase in frequency in patients with late graft failure. In
      keeping with results from experimental models of transplantation tolerance,
      evidence for allospecific regulatory cells was found in some patients with good,
      stable transplant function. Interestingly, the regulatory cells appeared to have
      indirect allospecificity, and no evidence of direct pathway regulation was
      observed. CONCLUSIONS: The indirect pathway anti-donor alloresponse poses the
      major threat to long-term transplant survival. Indirect pathway regulatory T
      cells arise in some patients. These data are consistent with the hypothesis that
      tolerance strategies require shrinkage of the direct, and regulation of the
      indirect, anti-donor response.

PMID- 15567921
TI  - Lymphocyte depletion as a barrier to immunological tolerance.
AB  - Lymphocyte depletion is a commonly used approach in clinical renal
      transplantation as part of standard induction immunosuppression therapy. It is
      also increasing being incorporated into new approaches aimed at inducing
      transplantation tolerance. While the theoretical basis for eliminating
      alloreactive T cells as a means to prevent rejection and induce tolerance is
      sound, new evidence suggests that global non-specific deletion may, by promoting
      the development of memory T cells, actually present a barrier to tolerance
      induction.

PMID- 15567922
TI  - Monitoring of immunosuppressive therapy in renal transplanted patients.
AB  - The regulation of the immunosuppressive therapy after kidney transplantation is
      the most complex aspect of the management of transplanted patients. Every day the
      transplant clinician is challenged by need to provide a sufficient
      immunosuppression to avoid or reduce the risk of rejection without exposing the
      patient to the risk of developing opportunistic infections or malignancy or toxic
      side effects. The safety and efficacy profile of immunosuppressive therapy is
      limited within a narrow therapeutic window whose borders are represented by two
      clinical conditions such as rejection and drug-related toxicity. The availability
      of several different drugs allows the clinicians to make multiple choices to
      individualize treatments according to the specific needs of a single patient.
      Pharmacokinetic monitoring of the immunosuppressive drugs is an important element
      in the management of these patients but cannot be considered as the unique
      driving factor and must be integrated with a careful surveillance and evaluation
      of all drug-related side effects.

PMID- 15567923
TI  - Chronic allograft nephropathy. A multiple approach to target nonimmunological
      factors.

PMID- 15567924
TI  - Transplantation tolerance. A complex scenario awaiting clinical applicability.
AB  - Organ transplantation is now firmly established as the therapy of choice for end
      stage organ failure. Specific immunological tolerance of transplant recipients
      towards their foreign organ or tissue grafts is a goal that has been sought by
      transplant biologists for almost 50 years following the original description of
      the phenomenon in experimental animals by Medawar and colleagues. Since that
      time, a wealth of experimental data has accumulated relating to strategies for
      extending allograft survival and function. Recent studies have shed new light on
      the molecular and cellular basis of transplant rejection and have better defined
      the mechanisms of allograft tolerance with particular emphasis on a role for
      regulatory T cells. Still, the question remains of how near we are to the day
      when long-term tolerance of engrafted organs or tissues will be a clinical
      reality. Recently, clinical trials to explore pilot tolerance protocols in humans
      have been initiated under the auspices of the Immune Tolerance Network
      (www.immunetolerance.org). In this review we will highlight the promise and
      challenges of making transplantation tolerance a clinical reality.

PMID- 15567925
TI  - Dendritic cells,tolerance and therapy of organ allograft rejection.
AB  - Donor dendritic cells (DCs) and those of host origin play key roles in the
      instigation and maintenance of immune responses to organ allografts. In the
      normal steady state, however, DCs are important for the maintenance of central
      and peripheral tolerance. Moreover, the presence of those cells in donor
      hematopoietic cell infusions may facilitate the induction of transplant
      tolerance. Accrual of information regarding DC tolerogenicity has driven the
      assessment of DC-based therapy of allograft rejection. Pioneering work
      demonstrating increased allograft survival after pretransplant infusion of
      immature donor-derived DC has prompted the evaluation of several approaches to
      the generation of DCs with tolerogenic/regulatory properties. These include:
      identification of specific culture conditions for propagation of homogenous
      populations of immature DCs; pharmacological manipulation of DCs to stabilize
      their immature/tolerogenic phenotype; and genetic modification of DCs to impair
      their stimulating ability/enhance their tolerogenicity. These approaches have
      rendered DCs capable of markedly prolonging experimental allograft (including
      kidney transplant) survival and promoting donor-specific tolerance. Recently
      identified molecular signaling pathways that play key roles in the outcome of DC
      T cell interaction are likely to become novel targets for manipulation of
      allograft immunity and for the promotion of transplant tolerance.

PMID- 15567926
TI  - Natural versus adaptive regulatory T cells.
AB  - It is now well recognized that regulatory T cells (Treg) play a central role in
      the control of both reactivity to self-antigens and alloimmune response. Several
      subsets of Treg with distinct phenotypes and mechanisms of action have now been
      identified. They constitute a network of heterogeneous CD4+ or CD8+T cell subsets
      and other minor T cell populations such as nonpolymorphic CD1d-responsive natural
      killer T cells. Treg not only play a main role in maintaining self-tolerance and
      preventing autoimmune disease but can also be induced by tolerance protocols and
      seemed to play a key role in preventing allograft rejection, as demonstrated in
      many animal models. Of particular interest, in stable transplant patients,
      CD4+CD25+ and CD8+CD28- Treg have been recently shown to modulate immune response
      toward donor antigens in the indirect and direct pathway, respectively. This
      finding raises the possibility that such Treg also have a role in the induction
      or maintenance of transplant tolerance in humans.

PMID- 15567927
TI  - Reviewing the mechanism of peripheral tolerance in clinical transplantation.

PMID- 15567928
TI  - The goal of intragraft gene therapy.
AB  - Despite the impressive results of one-year survival rates, organ transplantation
      still faces major problems. Current anti-rejection drugs reduce systemic immunity
      nonselectively and increase the risk of infection and cancer on the long term.
      Theoretically, selective inhibition of alloimmune response can be achieved at the
      organ level by intragraft transfer of genes with immunomodulatory properties. In
      the last decade, gene therapy emerged as a new strategy in renal, heart and liver
      transplantation, showing promising results in experimental animals, almost in
      controlling acute rejection. The success of gene therapy in the transplant
      medicine is strongly dependent on the efficiency of the delivery system that
      allows local transfer and expression of the therapeutic gene in the target organ
      or tissue. The main findings concerning the suitability of gene therapy in
      preventing graft rejection will be discussed here.

PMID- 15567929
TI  - [The topographical anatomy of the external branch of the superior laryngeal nerve
      and its importance in thyroid surgery: a cadaver study].
AB  - OBJECTIVES: We investigated topographical anatomic features of the external
      branch of the superior laryngeal nerve (SLN) in relation to the superior thyroid
      artery (STA) and its vulnerability to injury in individuals with a normal thyroid
      size. STUDY DESIGN: Thirty fresh cadavers (18 females, 12 males; age range 20 to
      50 years) with a normal thyroid size and no signs of abnormality in the neck were
      studied. The external branch of the SLN was identified and classified according
      to the system proposed by Cernea et al. RESULTS: The topographical relationship
      between the external branch of the SLN, the STA, and the upper pole of the
      thyroid gland was identified in 54 thyroid lobes (90%). Identification was not
      possible in six lobes because of bleeding or injury. The location of the external
      branch of the SLN was consistent with type 1 in 28 lobes (51.8%) and type 2 in 26
      lobes (48.2%; type 2a in 37.1% and type 2b in 11.1%). No significant
      relationships existed between the type of the nerve, gender, and age, nor was
      there any symmetry with regard to the location of the external branch of the SLN
      in the same subject. CONCLUSION: Nearly half of the Turkish population with a
      normal thyroid gland size present high surgical risks during thyroid surgery
      because of the course of the external branch of the SLN.

PMID- 15567930
TI  - [The incidence of level I metastasis in laryngopharyngeal squamous cell
      carcinoma].
AB  - OBJECTIVES: We investigated the incidence of level I metastasis in patients with
      laryngeal and hypopharyngeal squamous cell carcinoma (SCC). PATIENTS AND METHODS:
      The records of 126 patients who underwent primary tumor excision with radical
      neck dissection (RND) or its modifications for laryngeal or hypopharyngeal SCC
      were retrospectively reviewed. Preoperative tumor and neck stages, the sites and
      the number of metastatic lymph nodes were recorded. Patients treated with
      selective neck dissection (SND) or preoperative chemotherapy and/or radiation
      therapy were excluded. RESULTS: Of 155 RND or modified RND performed for 113
      laryngeal and 13 hypopharyngeal SCC, lymph node metastases were detected in 51
      specimens, all of which spared level I. The most frequently involved levels were
      II and III. CONCLUSION: Selective neck dissection sparing level I may be
      appropriate for clinically and radiologically N0 patients with laryngopharyngeal
      carcinoma.

PMID- 15567931
TI  - [The effects of pharyngeal neurectomy and cricopharyngeal myotomy on
      postoperative deglutition in patients undergoing horizontal supraglottic
      laryngectomy].
AB  - OBJECTIVES: We compared the effects of pharyngeal neurectomy (PN) and
      cricopharyngeal myotomy (CPM) on postoperative deglutition in patients undergoing
      horizontal supraglottic laryngectomy (HSL). PATIENTS AND METHODS: The study
      included 20 male patients (mean age 53 years; range 39 to 67 years) who underwent
      HSL for squamous cell carcinoma of the larynx. Tumor stages were T1 in two, T2 in
      16 , and T3 in two patients. None had received radiotherapy before surgery. In
      order to decrease cricopharyngeal muscle spasm following HSL, the patients were
      randomly chosen for CPM (n=11) and PN (n=9). The two groups were compared with
      respect to the time to postoperative oral food intake. RESULTS: No significant
      difference was found with respect to the time to postoperative oral feeding (mean
      27 days, range 16 to 45 days in the CPM group; mean 25 days, range 16 to 36 days
      in the PN group; p>0.05). No significant relationship existed between primary
      tumor stages and the time to oral feeding (p>0.05). No complications were
      encountered in the two patient groups. CONCLUSION: In supraglottic partial
      laryngectomies, PN seems to be as effective as CPM to decrease postoperative
      cricopharyngeal muscle spasm, with additional advantages of ease and safety.

PMID- 15567932
TI  - A case of congenital bilateral stapes agenesis.
AB  - Congenital absence of the stapes and the oval window is an anomaly reported in
      only sporadic cases. We present a 17-year-old male patient with congenital
      bilateral conductive hearing loss. The external auditory canal and the tympanic
      membrane appeared normal on both sides. An exploratory tympanotomy in the right
      ear revealed dehiscence of the the horizontal segment of the facial nerve, which
      was displaced inferiorly, occupying the area of the absent oval window. The
      stapes was totally absent and a malformed long process of the incus was attached
      by a fibrous band to the promontory. Manipulation of the facial nerve in
      association with stapedectomy or vestibulotomy was avoided in order not to injure
      the nerve. Instead, amplification with hearing aids was recommended to the
      patient.

PMID- 15567933
TI  - Bilateral second branchial cleft cysts without any associated congenital
      abnormality: a case report.
AB  - A thirty-year-old male patient with bilateral second branchial cleft cysts is
      presented, in whom no association was found with any other congenital
      abnormality, in particular branchio-oto-renal syndrome. He had a complaint of
      painless swelling on both sides of the neck. Physical and radiological
      examinations showed bilateral branchial cleft cysts. A coexisting congenital
      syndrome could not be documented despite investigations including physical
      examination, blood biochemistry and complete blood count, audiologic tests,
      temporal bone computed tomography, and abdominal and renal ultrasonography.
      Surgical excision was performed on both sides with a three-week interval.
      Histopathologic examination confirmed the diagnosis. The postoperative period was
      uneventful, with no recurrence during a follow-up period of 12 months.

PMID- 15567934
TI  - A case of granulocytic sarcoma during complete remission of acute myeloid
      leukemia with multiple masses involving the larynx and nasopharynx.
AB  - A thirty-seven-year-old male patient presented with dysphagia and hoarseness six
      months after complete remission of acute myeloid leukemia (AML-M0), which had
      been treated with chemotherapy. Physical examination revealed left vocal cord
      paralysis and involvement of the 9th, 10th, and 12th cranial nerves. Sagittal and
      axial magnetic resonance scans of the nasopharynx and neck showed a mass in the
      left retropharyngeal and perivertebral regions, 6x4 cm in size; another mass in
      the left vallecula, and infiltration of the right preepiglottic tissue by another
      mass of 2 cm. There was no bone marrow involvement. A diagnosis of granulocytic
      sarcoma without leukemia relapse was made and the FLAG-Ida regimen was
      administered, after which partial regression of the masses was observed. However,
      the patient died due to a pulmonary infection on the 17th day of chemotherapy.

PMID- 15567935
TI  - Plasma leptin and breast cancer risk: a prospective study in northern Sweden.
AB  - INTRODUCTION: Obesity is associated with risk of breast cancer after menopause.
      Circulating levels of leptin are high in obesity and leptin stimulates growth of
      breast cancer cells. MATERIAL AND METHODS: In a case-control study nested within
      the Northern Sweden Health and Disease Cohort, we measured leptin levels in
      prediagnostic plasma from 149 postmenopausal women who were diagnosed with breast
      cancer at a mean time 1.7 years (SD 2.0) after recruitment and among 258 control
      subjects. RESULTS: No significant association between plasma levels of leptin and
      breast cancer risk was observed. Odds ratios (ORs) of breast cancer with
      increasing levels of leptin were 1.00 [referent], 1.01 [95% CI = 0.58-1.84], 0.65
      [0.36-1.18], and 0.94 [0.53-1.67], and (p(for trend) = 0.54). Adjustment for
      smoking, body mass index, and plasma insulin did not affect risk estimates.
      DISCUSSION: These data do not support the hypothesis that plasma leptin is a risk
      factor for breast cancer.

PMID- 15567936
TI  - HER-2/neu as a predictive marker in a population of advanced breast cancer
      patients randomly treated either with single-agent doxorubicin or single-agent
      docetaxel.
AB  - PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced
      breast cancer patients randomly treated either with single-agent doxorubicin (A)
      or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study
      participated in a phase III clinical trial in which doxorubicin or docetaxel was
      administered for advanced disease. HER-2 was evaluated by IHC. In all positive
      cases, FISH was used to confirm the HER-2 positive status. The different cohorts
      of patients identified by HER-2 were examined to assess a possible relationship
      between HER-2 status and treatment effect. RESULTS: Tumor samples were available
      for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity
      was observed in 20% of the study population. A statistically significant
      interaction was found between response rates to the study drugs and HER-2 status,
      with HER-2 positive patients deriving the highest benefit from the use of T (odds
      ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p =
      0.03). The interaction between HER-2 and response rates to A and T was also
      confirmed by a multivariate analysis. No statistically significant interaction
      was found between HER-2 and drugs efficacy evaluated in terms of time to
      progression and overall survival, although in the HER-2 negative cohort A was at
      least as effective as T in term of overall survival. CONCLUSIONS: These results
      suggest that in HER-2 positive breast cancer patients docetaxel might be more
      active than doxorubicin, while in HER-2 negative patients doxorubicin might be at
      least as effective as docetaxel. Although the present results cannot have an
      impact on current practice, they allow us to formulate the hypothesis that HER-2
      positive breast cancer is a heterogeneous disease with regard to sensitivity to
      anthracyclines and taxanes, and that this might be dependent upon other molecular
      markers including the p-53 and topoisomerase II alpha genes. This hypothesis is
      currently being tested prospectively in two different 'bench to bed-side'
      clinical trials.

PMID- 15567937
TI  - High Ep-CAM expression is associated with poor prognosis in node-positive breast
      cancer.
AB  - Previous studies in small series of patients with invasive breast cancer
      suggested a prognostic value of Ep-CAM overexpression in primary tumor tissue. To
      corroborate these findings, we performed a retrospective analysis of Ep-CAM
      expression using a tissue microarray containing tissue specimens from a large
      patient set. Ep-CAM expression was evaluated by immunohistochemistry in breast
      cancer tissue from 1715 patients with documented raw survival data. High level Ep
      CAM expression (overexpression) was found in 41.7% of tumor samples, low level
      expression was found in 48.0% and no expression in 10.3% of tumor samples. Ep-CAM
      expression predicted poor overall survival in this patient cohort (p < 0.0001).
      Overall survival decreased significantly with increasing Ep-CAM expression.
      However, in this patient sample Ep-CAM expression was not an independent
      prognostic marker by multivariate analysis. Subgroup analysis revealed that Ep
      CAM expression was a prognostic marker in node-positive (p < 0.0001) but not in
      node-negative (p = 0.58) breast cancer patients. Intriguingly, Ep-CAM expression
      was predictive for a dismal prognosis in patients receiving adjuvant cytotoxic (p
      = 0.03) or hormonal therapy (p < 0.0001) but not in untreated patients (p =
      0.41). In summary, this study provides strong evidence that expression of Ep-CAM
      is a powerful marker of poor prognosis in node-positive invasive breast carcinoma
      and a potential predictive marker of sensitivity to adjuvant hormonal and/or
      cytotoxic treatment modalities.

PMID- 15567938
TI  - Reproducible immunohistochemical criteria based on multiple raters' judgments for
      expression of thymidine phosphorylase in breast cancer tissue.
AB  - In order to accurately determine the expression of thymidine phosphorylase (TP)
      in breast cancer, it is important to develop an appropriate system for
      immunohistochemical staining evaluation. Three raters, pathologists A-C,
      independently judged the status of TP in both cancer cells and cancer stromal
      tissue in 586 breast cancers immunohistochemically. TP expression levels were
      categorized into four groups (scores 0-3), and scores of 2 and 3 were considered
      as positive. Interrater and intrarater agreement levels in the judgment of TP
      expression were analyzed by the kappa statistics. By combining three raters'
      judgments, we sought for the optimal evaluation system that generates the best
      concordance among all judgments. The numbers of TP-positive cases were 294
      (50.2%), 309 (52.1%) and 344 (58.7%) for cancer cells and were 315 (53.8%), 383
      (65.4%) and 397 (67.7%) for cancer stromal tissue in the judgments by
      pathologists A, B, and C, respectively. There was no correlation of TP
      immunostaining between cancer cells and cancer stroma tissue. Interrater
      agreement levels were substantial for cancer cells (kappa = 0.652) and moderate
      for cancer stroma tissue (kappa = 0.438). Intrarater agreement level for TP
      judgment by pathologists A, B, or C was substantial to almost perfect for cancer
      cells (kappa = 0.755-0.880), and for cancer stromal tissue (kappa = 0.620-0.752).
      The level of TP expression estimated under the majority system and the total
      scoring system setting a cut-off score between 4 and 5 revealed the highest
      concordance with the three raters' judgments. To accurately evaluate the TP
      status in breast cancer tissue, three or more raters are needed and the majority
      system and total scoring system appear appropriate.

PMID- 15567939
TI  - High-fat corn oil diet promotes the development of high histologic grade rat DMBA
      induced mammary adenocarcinomas, while high olive oil diet does not.
AB  - Effects of a high corn oil and a high olive oil diet on the histopathologic
      characteristics of rat dimethylbenz(alpha)anthracene-induced mammary
      adenocarcinomas were investigated in comparison with those of a control low-fat
      diet. Two experimental series (A and B) studied the influence of a high corn oil
      diet on the initiation and the promotion of mammary carcinogenesis, while another
      one (C) assessed the effects of the two dietary lipids on the promotion. Nine
      parameters have been analyzed and a new histologic grading method, adapted to rat
      tumors, has been applied in each carcinoma. High corn oil diets, particularly
      when acting as promoters, associated with higher-grade carcinomas than control (p
      < 0.05) and high olive oil groups. Stromal invasion and tumoral necrosis were
      more prominent and a prevailing cribriform pattern was observed (p < 0.05). High
      olive oil diet adenocarcinomas exhibited a predominantly low histologic grade and
      few necrotic and invasive areas, similar to the control, and they presented the
      highest percentage of papillary areas. Lymphoplasmacytic and mast cell
      infiltration were also influenced by the dietary lipids. Thus, high corn oil diet
      adenocarcinomas presented a higher degree of morphological malignancy than
      control and high olive oil tumors, which is in line with the greater clinical
      malignancy described in rats from the former group and the non-promoting effect
      of the high olive oil diet. As far as we are concerned, a similar histopathologic
      approach of the effects of the dietary lipids on experimental breast cancer has
      not been carried out up to now.

PMID- 15567940
TI  - Enumeration of circulating tumor cells in the blood of breast cancer patients
      after filtration enrichment: correlation with disease stage.
AB  - The biological and clinical significance of circulating tumor cells (CTC) in the
      peripheral blood of breast cancer patients is not known. To study this question,
      we used a direct visualization assay to correlate the number of CTC with disease
      stage and progression. The CTC were enriched from the nucleated cell fraction by
      filtration and enumerated visually following immunostaining with anti-cytokeratin
      8 (CK8) antibody CAM 5.2. In mixing experiments, we achieved a limit of detection
      of 5 MCF7 cells per 5 ml of blood or 5 x 10(7) peripheral blood leukocytes (PBL).
      We did not detect CTC in any control subjects (0/20). In 131 breast cancer
      patients, we found a higher incidence of CTC in patients with distant metastatic
      36/51 (71%) than those with node-positive 17/36 (47%) (p = 0.026), or node
      negative 17/44 (39%) (p = 0.001) disease. The distribution of the highest numbers
      of CTC observed in individual patients by repeated sampling over time ranged from
      1 to 700 per 5 ml of blood with a trend toward higher numbers in those with
      distant metastases. In comparison with previous studies of equal specificity,
      based on a similar absence of CTC in controls, we report a higher incidence of
      CTC in node-negative and node-positive patients, suggesting a more frequent
      detection of CTC by our approach. This higher incidence was achieved, in part, by
      repeated sampling of our study population over time. Our results support the
      concept that CTC can be detected and enumerated in peripheral blood and that this
      minimally invasive assay merits further evaluation as a potential prognostic
      indicator and marker of disease progression.

PMID- 15567941
TI  - Safety and activity of the combination of pegylated liposomal doxorubicin and
      weekly docetaxel in advanced breast cancer.
AB  - BACKGROUND: The present study was designed with the aim of evaluating the
      tolerability and activity of pegylated liposomial doxorubicin (PLD) in
      combination with weekly docetaxel as first line treatment of advanced breast
      cancer. PATIENTS AND METHODS: Fifty-seven patients entered the study. PLD was
      administered at escalating doses starting from 30 mg/m2, on day 1; docetaxel was
      administered at the fixed dose of 35 mg/m2 on days 2 and 9. A cycle of therapy
      consisted of 21 days. RESULTS: The MTD was achieved at the dose of 40 mg/m2 of
      PLD, being febrile neutropenia and palmar-plantar-erythrodisesthesia (PPE) the
      dose-limiting toxicities (DLTs), so that the fixed dose of PLD for the Phase II
      study was 35 mg/m2. Forty-two consecutive patients received treatment at the
      established dose for a total of 194 cycles: among these, three patients were
      withdrawn for severe allergic reaction at the first administration of PLD.
      Hematological toxicity was moderate, the most common grade 1-3 non-hematological
      toxicities were stomatitis and PPE, occurring in 20 (47.5%) and 16 (38%)
      patients, respectively. No cardiac toxicity was recorded. According to the intent
      to treat analysis a major objective response was observed in 59.5% of patients
      (95% CI, 43.3-74.4%), with a median time to progression of 9 months and an
      estimated overall survival at 18 months of 62%. CONCLUSION: The combination of
      PLD and weekly docetaxel is an effective first-line therapy for patients with
      advanced breast cancer. PPE and mucositis are the most relevant side effects of
      such a combination.

PMID- 15567942
TI  - Normal breast lobular architecture in breast biopsy samples from breast cancer
      cases and benign disease controls.
AB  - Rodent studies suggest a relationship between lobular maturation and breast
      cancer risk. Human data are sparse, and were developed using whole mounts of
      mastectomy or mammoplasty samples, without consideration of menstrual phase in
      premenopausal women. We studied normal breast lobules in relation to cancer risk
      in 284 women, using surgical biopsy material (mean two sections and 43.2 lobular
      structures per subject): 167 were premenopausal; 89 with breast cancer (cases)
      and 78 undergoing benign breast biopsy (controls). Of 117 postmenopausal women,
      67 were cases and 50 were controls. Normal lobular type was classified based on
      size, and was designated predominant if it constituted 60% or more of the total
      lobules classified. The control group showed 66% type I, 34% type II and 1% type
      III lobules while cases showed 69% type I, 31% type II and 7% type III
      structures. Predominant lobule type showed no association with cancer (p = 0.9).
      Postmenopausal women had a substantially higher proportion of type I lobules
      compared to premenopausal women, irrespective of the parity or cancer status (p <
      0.001). Lobule type was not associated with menstrual phase classified by dates;
      however, when menstrual phase was classified using breast morphological
      characteristics, type I lobules were more abundant in follicular phase and type
      II in the luteal phase (p < 0.001). In conclusion, we did not observe a
      relationship between lobular architecture and breast cancer susceptibility when
      using smaller breast samples usually available in epidemiological studies, but
      these data highlight the need for menstrual phase stratification in future
      investigations.

PMID- 15567943
TI  - Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast
      cancer cells from TRAIL-induced apoptosis.
AB  - Advanced breast cancer is often associated with metastatic bone disease, causing
      a number of serious complications for the patients such as hypercalceamia, pain,
      nerve compression and fractures. The formation of bone metastases depends on
      complex interactions between tumour cells and the cells of the bone
      microenvironment, but the precise molecular mechanisms involved in the
      development of tumour-induced bone disease have not been identified. We have
      investigated the ability of bone marrow stromal cells (BMSC) isolated from breast
      cancer patients to generate osteoprotegerin (OPG), a molecule involved both in
      bone turnover and cell survival. The potential survival effects of OPG are
      mediated through binding to a member of the TNF super family, TNF-related
      Apoptosis Inducing Ligand (TRAIL), preventing association between TRAIL and its
      death-inducing receptors present on a number of tumour cell types. In the present
      report we show that bone marrow stromal cells isolated from breast cancer
      patients produce OPG when grown in culture. The levels of OPG present in BMSC
      conditioned medium is sufficient to protect breast cancer cells from undergoing
      TRAIL induced apoptosis. Our data suggest that bone-derived OPG may increase
      survival of breast cancer cells that reach the bone microenvironment as part of
      the metastatic process.

PMID- 15567944
TI  - Use of high-throughput protein array for profiling of differentially expressed
      proteins in normal and malignant breast tissue.
AB  - cDNA arrays provide a powerful tool to identify gene expression pattern that are
      potentially associated with tumor invasion and metastasis. However, genes work at
      the protein level and, since the transcriptional activity of a gene does not
      necessarily reflect cellular protein expression, the identification and
      quantification of proteins is essential for the understanding of molecular events
      leading to malignant transformation. We have therefore employed a high-throughput
      protein microarray system which contains 378 well-characterized monoclonal
      antibodies in order to compare the gene expression pattern of malignant and
      adjacent normal breast tissue in a patient with primary breast cancer. Using this
      technique, we have identified a number of proteins that show increased expression
      levels in malignant breast tissues such as casein kinase Ie, p53, annexin XI,
      CDC25C, eIF-4E and MAP kinase 7. The expression of other proteins, such as the
      multifunctional regulator 14-3-3e was found to be decreased in malignant breast
      tissue, whereas the majority of proteins remained unchanged when compared to the
      corresponding non-malignant samples. The protein expression pattern was confirmed
      by immunohistochemistry, in which antibodies against 8 representative proteins
      known to be involved in carcinogenesis were employed in paraffin-embedded normal
      and malignant tissue sections deriving from the same patient. In each case, the
      results obtained by IHC matched the data obtained by antibody microarray system.
      Taken together, we have described for the first time a tumor cell specificity
      protein expression pattern by use of a novel commercially available antibody
      microarray system. We have thus demonstrated the feasibility of high-throughput
      protein arrays in the proteomic analysis of human breast tissue. We hypothesize
      that the use of protein arrays will not only increase our understanding of the
      molecular events, but could prove useful in evaluating prognosis and in
      determining optimal antineoplastic therapy.

PMID- 15567945
TI  - [Should the classification of ampullar tumors be revisited?].

PMID- 15567946
TI  - [Cytokeratins 7 and 20 immunohistochemistry in ampullary carcinomas].
AB  - Ampullary carcinomas (AC) account for 33% of all surgically operable
      pancreatoduodenal tumors. The 5-year relative survival rate is 50% and tumoral
      stage is the main prognostic factor. However, among the three AC histological
      subtypes (intestinal, pancreatobiliary and mixed), a favorable prognostic has
      been reported for the intestinal subtype. BACKGROUND: The aims of this study were
      to determine the prognostic impact of AC histologic subtype and of cytokeratins
      (CK) 7 and 20 immunostaining profile in these tumors. PATIENTS AND METHODS:
      Clinical data of 54 AC were obtained retrospectively. Macroscopic and histologic
      documents were reviewed and immunostainings for CK7 and CK20 were performed.
      RESULTS: The classification of tumors, according to histological subtype, was:
      intestinal 26%, pancreatobiliary 65% and mixed 9%. No correlation was found
      between histological subtype and tumor stage. The 5-year survival rate varied
      from 100% for intestinal subtype to 35% for pancreatobiliary subtype. A strong
      correlation (p < 0.0001) was found between histological subtype and CK7/CK20
      immunostaining profile. The 5-year survival rate varied from 100% for CK7-/CK20 +
      AC to 40% for CK7 + /CK20- AC. CONCLUSION: In our study, the intestinal
      histological subtype had a favorable prognostic value. CK7/CK20 immunostaining
      profile was helpful for the identification of histological subtype and appears to
      provide additional prognostic information.

PMID- 15567947
TI  - [P63 protein in the diagnosis of breast tubular carcinoma].
AB  - AIMS: To study and compare the expression of p63 protein and smooth muscle actin
      in breast tubular carcinoma (TC) and its main differential diagnoses, radial scar
      (RS)/complex sclerosing lesion (CSL). MATERIALS AND METHODS: Immunohistochemistry
      techniques were used to search for p63 protein and smooth muscle actin antibodies
      in 10 patients with TC and fifteen with RS/CSL. RESULTS: Myoepythelial cells were
      diffusely positive for both actin and p63 protein with a cytoplasmic (actin) or
      nuclear (p63) pattern in all patients with RS/CSL. Inversely, all TC were
      negative for p63. Actin antibodies failed to label myoepithelial cells in TC, but
      both vessels and stromal myoblasts were actin-positive, creating difficult
      interpretation situations. By contrast, p63 was consistently negative in these
      structures. CONCLUSION: For the differential diagnosis between TG and CR/LSC,
      smooth muscle actin and p63 protein demonstrate equivalent sensitivity for the
      detection of myoepithelial cells. However, the nuclear pattern of p63 labeling
      gives a "cleaner" stain. In addition, p63 enables distinction between
      myoepithelial cells and myofibroblasts/vascular smooth muscle cells, offering
      increased specificity.

PMID- 15567948
TI  - [Cervical intraepithelial neoplasia (CIN) in Brazzaville, Congo. A situation
      analysis].
AB  - OBJECTIVE: To collect epidemiological data about Cervical Intra epithelial
      Neoplasia in Brazzaville, for planning strategic issues of a cancer screening
      programme in the Congo. METHODS: Retrospective study of the results of 5700
      occasional cervical Pap smears. RESULTS: The majority of the recorded women were
      21 to 30 years old (49%), with a single or multiple parity (83.20%), and with a
      low socio-economic status. Among the 3088 recorded pathological smears, 200 cases
      of CIN were identified predominantly in 20 to 29 year-old-patients. They were
      subdivided into 174 (87%) CIN I, and 26 (13%) CIN II and CIN III. On the same
      occasion, 88 invasive cancers have been observed, predominantly among 50 to 60
      year-old-women; an interval of 10 years has thus been noted between the latest
      period when CIN occurred (30 to 39 years) and the period when most of invasive
      cancers came about. CONCLUSIONS: The interest of an organized national screening
      programme has thus been confirmed. The formulation of a national cancer strategic
      plan requests an updating of the present database with the results of additional
      epidemiological (cytological, virological) studies concerning hight-grade
      intraepithelial lesions, and by those of a national health system analysis
      concerning health of women in the post-reproductive period.

PMID- 15567950
TI  - [Classical Hodgkin's lymphoma: biology and grey zones].
AB  - Advances in the biology of Hodgkin's lymphoma have lead to the distinction
      between two entities, "classical" Hodgkin's lymphoma and nodular lymphocyte
      predominance Hodgkin's lymphoma, previously called nodular paragranuloma, which
      share distinct clinical aspects. The definition of diagnostic criteria has also
      been helpful to separate Hodgkin's lymphoma from other lymphomas which can mimick
      Hodgkin's disease such as anaplastic large cell lymphomas, T-cell/histiocyte rich
      diffuse large B-cell lymphoma, and some peripheral T-cell lymphomas, mainly
      angioimmunoblastic-type. Reed-Sternberg cell, the neoplastic cell of "classical"
      Hodgkin's lymphoma, still retains some secrets. Despite some controversies, there
      is more and more evidence for a lymphoid B cell origin. The involvement of
      Epstein-Barr virus, cytokines and/or oncogenes expression in the pathogeny can be
      suggested, although the precise mechanisms leading to transformation and/or
      accounting for tumour progression are still elusive. Recently, the roles of the
      pathway implicating the activation of NFkappaB as well as the autocrine secretion
      of interleukin-13 have been demonstrated.

PMID- 15567951
TI  - [Alveolar capillary dysplasia with misalignment of pulmonary vessels].
AB  - Alveolar capillary dysplasia (ACD), with or without pulmonary vein misalignment
      is a uniformly fatal cause of persistent pulmonary hypertension and respiratory
      failure, first described in 1981. We report the case of ACD in a full term
      newborn with post mortem pathologic confirmation. Sixty five cases have been
      reported in the literature, most are sporadic, but a few cases of familial ACD
      suggest an autosomal recessive inheritance. In 55% of the reported cases of ACD
      other cardiovascular, digestive or urogenital anomalies were associated. ACD is
      presumed to be a primary capillary disorder. It affects full-term neonates who
      exhibit respiratory distress during the early post natal period due to pulmonary
      hypertension and die within 3 weeks of birth. Histologic findings include a
      decrease in the number of alveolar capillaries, which are placed centrally within
      the intralobular septa, ectatic veins accompany the bronchovascular bundles
      instead of being in their normal position in the interlobular septum, and
      muscularized pulmonary arteries extend to the distal level. Prognosis is very
      poor, intravenous prostacyclin with inhaled nitric oxide have been reported in
      the cases with the best survival.

PMID- 15567952
TI  - [The value of cytology in the diagnosis of extragonadal germ cell tumors].
AB  - Extragonadic germinal tumors are frequently mixed tumors. When a metastatic
      sacrococcygeal teratoma is clinically suspected in children, a yolk-sac tumor
      component could be judiciously demonstrated by either an elevated serum level of
      alphafoetoprotein (AFP), or fine needle aspiration cytology. We report the case
      of a 25 month aged girl presenting a metastatic sacrococcygeal tumor (lymph node
      and bone metastasis) with high level of AFP (34.100 microg/ml). Fine needle
      aspiration cytology identified the yolk sac tumor component, characterized by
      papillae and glandular clusters, composed of pale isomorphic cells with vesicular
      and nucleolated nucleus and some intracytoplasmic hyaline globules. The yolk sac
      tumor component could not be identified in the sacrococcygeal surgical specimen,
      exclusively composed of immature teratoma.

PMID- 15567953
TI  - [An unusual cause of multiple hepatic cysts].
AB  - A metastatic hepatic process, generally arising from a primary tumor of the
      gastrointestinal tract, is a common cause of multinodular and/or multicystic
      liver. If the primary tumor remains unknown in spite of complete and exhaustive
      explorations, it might be useful to re-evaluate the benign nature of previously
      resected tumors. We report the case of a 37 year-old woman who presented a
      multicystic metastatic liver related to a nasal cylindrical cell carcinoma
      resected 4 years earlier and diagnosed initially "inverted papilloma".
      Cylindrical cell carcinoma also called "transitional carcinoma" or "schneiderian
      carcinoma" is rare with only a few cases reported in the literature. Metastases
      occur generally in the lungs and no previous reported cases mention secondary
      hepatic location.

PMID- 15567954
TI  - [Malignant biliary papillomatosis: analysis of p53 expression].
AB  - Biliary papillomatosis is a papillary adenomatosis of the biliary mucosa of the
      extra- and the intrahepatic biliary tree. It is a rare neoplasm difficult to
      manage, characterized by extensive lesions and a great potential for malignant
      transformation. We report a case of a 75 year-old man, who presented with
      malignant papillomatosis of the common bile duct without involvement of the
      intrahepatic biliary ducts. Duodenopancreatectomy enabled the diagnosis of
      papillomatosis lined 5.5 cm of the common bile duct which displayed an invasive
      1.5 cm papillary carcinoma located in the distal portion of the choledocus.
      Immunohistochemistry showed strong expression of p53 in the distally located
      invasive carcinoma and in distant dysplastic lesions. MUC5AC was exclusively
      detected in both malignant and dysplastic lesions without detection of MUC1 or
      MUC2. Detection of p53 expression on biliary brush samples could be interesting
      for the follow-up and the prediction of malignant progression in multifocal
      biliary papillomatosis.

PMID- 15567955
TI  - [Onychomatricoma, a rare lesion of the nail].
AB  - Onychomatricoma is a rare fibroepithelial lesion of the nail matrix with peculiar
      clinical and histological features. Clinically, it is characterized by a
      longitudinal band of yellow thickening of the nail plate with transverse
      overcurvature and splinter hemorrhages. Nail avulsion exposes a villous tumor of
      the matrix with filamentous digitations extending into multiple holes of the nail
      plate. Histologically, a thick keratogenous zone forms a thickened nail plate.
      The lesion in its proximal portion is characterized by deep epithelial
      invaginations and by a stroma organized in two layers. The distal zone
      corresponds to multiple fibroepithelial projections extending into the nail
      plate. The diagnosis can be difficult in the presence of misleading clinical
      features or when the specimen is incomplete or examined with an improper
      orientation. Surgical resection is the recommended treatment.

PMID- 15567956
TI  - [Primary adrenal angiosarcoma].
AB  - We report the case of a 69-year-old man who presented with an adrenal
      angiosarcoma which had been discovered during prostatic adenocarcinoma staging.
      Twenty-two cases have been reported in the literature. All of them were of
      epithelioid type. Because of the epithelioid appearance and frequent expression
      of epithelial immunohistochemical markers, they can be confounded with adrenal
      carcinomatous metastases. Careful screening for vascular differentiation and
      immunohistochemistry with endothelial markers are essential for the diagnosis.

PMID- 15567957
TI  - [Image in pathology].

PMID- 15567958
TI  - [A rare tumor of the rhinopharynx].

PMID- 15567959
TI  - [A pelvic cold abscess].

PMID- 15567960
TI  - [A not so common testicular tumor].

PMID- 15567961
TI  - [An unusual testicular torsion in a teenager].

PMID- 15567962
TI  - [Severe sensorineural impairment in very premature infants: epidemiological
      aspects].
AB  - OBJECTIVE: Advances in perinatal care have resulted in a sharply increasing
      survival rate among very preterm infants. However, there is some concern about
      the later neurodevelopmental outcome of those infants who survive. In this paper,
      we review the prevalence estimates of motor (cerebral palsy), sensorineural and
      cognitive impairments and their recent time-trends in very preterm infants.
      METHOD: A review of studies describing neurodevelopmental outcome of very preterm
      infants in Europe, Australia and America North. RESULTS: The gestational age
      specific prevalences of cerebral palsy (CP) were 72-86 for extremely preterm
      children (<28 weeks), 32-60 for very preterm (28-31 weeks) and 5-6 for moderate
      preterm (32-36 weeks), and 1.3-1.5 for term children per 1000. The live birth
      prevalence for CP remained unchanged in extremely and very preterm infants since
      1990. The prevalence estimates of moderate and severe cognitive impairments are
      15 to 25% in very preterm children. Less than 4% of very preterm infants develop
      severe hearing or visual loss. CONCLUSION: This review indicates that very
      preterm infants have high risk of disability. Most studies have been conducted
      between 1985 and 1995. Thus, these results should be interpreted with caution
      before generalisation to recent cohorts.

PMID- 15567963
TI  - [Developmental problems of very premature children at school age. Review of the
      literature].
AB  - Advances in perinatal care have lead to the survival of an increasing number of
      children born very premature. The purpose of this review is to discuss findings
      in the literature regarding long term developmental outcome of infants born
      prematurely especially for studies with children at least 5 years old, born in
      the 80's or after, in a context of care with increased use of antenatal
      corticoids, in utero transfer, and surfactant therapy. Developmental sequelae,
      which are seen in children older than those presenting severe deficiencies,
      concerns a greater number of very premature children. They have poorer outcomes
      than term children or normal birth weight controls for cognitive
      neuropsychological skills, school performances and behavior. Long term follow up
      of these children shows that consequences are still present for adolescents or
      young adults. There is a gradient of developmental sequelae in children that is
      inversely related to decreasing gestational age or birth weight. Developmental
      sequelae are related to neonatal medical complications and social risks factors.
      Research should be conducted in order to better understand etiology and
      neuropathological basis of sequelae, and the long term developmental implication
      of being born very premature and the type of care or intervention which could
      improve their development. An early and regular follow up by a team specialized
      in child development should be proposed in order to detect developmental sequelae
      and propose early intervention.

PMID- 15567964
TI  - [Surgical site infections after cesarean section: results of a five-year
      prospective surveillance].
AB  - AIMS: To determine the incidence of surgical site infections and to identify risk
      factors for infections. METHOD: A prospective study of surgical site infections
      (SSI) after cesarean section was carried out from September 1997 to September
      1998 (pilot study) and from January 2000 to August 2003, using the methodology of
      the American National Nosocomial Infection Surveillance System. Follow up of
      women was performed by midwives until discharge and during the post-natal visit.
      Suspected surgical site infections were confirmed by surgeons and infection
      control practitioners. The microbiological file of each patient was edited 30
      days after cesarean section. Risk factors were analyzed using a logistic
      regression model. RESULTS: During the pilot study, infection rate was estimated
      at 3.2%. At multivariate analysis, factors independently associated with an
      increased risk of SSI were ASA score > 1, performance of cesarean section in a
      room not dedicated to this activity, and use of an open urine drainage system.
      During the following years (2000-2003), infection rates progressively decreased
      to reach 1.9% in 2003. Infections included superficial wound infections
      (involving skin and subcutaneous tissue) (47%), deep wound infections (involving
      deep and soft tissue (fascia and muscle) (20%) and organ/space infections (i.e.
      endometritis, pelvic abscess) (33%). Infections occurred after patient discharge
      in 47.5% of cases and diagnosis was based only on clinical findings in 30% of
      cases. Infected patients were hospitalized longer (median: 6 days) than non
      infected patients. CONCLUSION: Prospective surveillance of SSI led to better
      awareness of infectious problems among health care workers, to identification of
      risk factors and evaluation of health procedures. Surveillance contributed to a
      decrease in nosocomial infections.

PMID- 15567965
TI  - [Factors associated with fecal incontinence after childbirth. Prospective study
      in 525 women].
AB  - OBJECTIVE: To determine the prevalence of fecal incontinence after childbirth and
      to identify the risk factors. METHODS: This was a prospective observational study
      with a consecutive inclusion of 525 women who delivered over a three months
      period. Women were questioned about their fecal continence four days and six
      weeks after delivery. RESULTS: The incidence of fecal incontinence four days and
      six weeks after childbirth was respectively 8.8% and 3.3%. The risk factors for
      fecal incontinence at 4 days after childbirth were instrumental delivery by
      forceps (adjusted odds ratio 8.64, 95% confidence interval 3.55-21.0, p < 0.001)
      and unassisted delivery at home (adjusted OR 8.06, 95% CI 1.30-50.0, p = 0.025).
      Independent risk factors for the presence of fecal incontinence 6 weeks later
      were: instrumental forceps delivery (adjusted OR 10.8, 95% CI 2.82-41.3, p =
      0.001), unassisted delivery at home (adjusted OR 50.0, 95% CI 3.09-802, p =
      0.006), bi-parietal diameter of the newborn > 93 mm (adjusted OR 4.56, 95% CI
      1.46-14.1, p = 0.009) and maternal age >30 years (adjusted OR 4.60, 95% CI 1.11
      19.1, p = 0.036). CONCLUSION: Fecal incontinence is common after childbirth and
      its prevalence is predominantly associated with instrumental delivery, unassisted
      delivery at home, bi-parietal diameter of the newborn and maternal age.

PMID- 15567966
TI  - [Severe maternal anemia and pregnancy outcome].
AB  - OBJECTIVES: The aim of this study was to determine the effects of severe
      antenatal maternal anemia on pregnancy outcome. MATERIAL: and methods. A
      retrospective study comparing 2 groups of pregnant women: 111 (pregnant women)
      with anemia (Hb < 8 g/dl), 111 non- anemic pregnant women (Hb >10 g/dl). Clinical
      and biological characteristics for both groups were compared. Data on the newborn
      babies were collected. RESULTS: In the anemic group: iron deficiency was the most
      common cause of anemia (92.7%). There was no significant difference between the 2
      groups with respect to age or parity. Maternal anemia was found to be
      significantly associated with more frequent preterm birth (29.2% vs 9.2%) and
      increased low birth weight (2933 g vs 3159 g). DISCUSSION: The literature is not
      conclusive on the influence of anemia in pregnant women. More frequent preterm
      birth and low birth weight have been reported in the majority of studies
      considering mild to moderate maternal anemia (in contrast to our study where the
      mothers had severe anemia). Many studies indicated that routine iron
      supplementation during pregnancy may have beneficial effects on pregnancy
      outcome. Severe anemia in pregnancy may have adverse effects for the newborn and
      should be treated or prevented early in pregnancy.

PMID- 15567967
TI  - [Magnesium sulfate in obstetrics: current data].
AB  - OBJECTIVE: To review the available evidence regarding history, pharmacology,
      physiology, maternal/fetal side effects, and efficacy of magnesium sulfate in
      pregnant women. DATA SOURCES: The literature in Medline was searched from 1966
      through April 2003 using the terms "magnesium sulfate," "tocolytic,"
      "preeclampsia," "eclampsia," and "pregnancy." Reviews of bibliographies of
      retrieved articles provided additional references. RESULTS: Magnesium sulfate
      (MgSO4) has long been used for prophylaxis of preterm delivery (tocolytic affect)
      and eclampsia prophylaxis (neuroprotective effect). Randomized controlled trials
      and systematic reviews have demonstrated the efficacy of magnesium sulfate in
      preventing eclampsia in patients with preeclampsia or in patients with eclampsia.
      Whether magnesium sulfate should be administered to patients with severe
      preeclampsia or to mild preeclampsia is discussed in the manuscript. Inversely,
      it appears that magnesium sulfate is ineffective in delaying birth or preventing
      preterm birth when it is used as a tocolytic. Furthermore, there is evidence that
      high cumulative doses of magnesium sulfate may be associated with increased
      infant mortality. CONCLUSION: The evidence to date confirms the efficacy of
      magnesium sulfate therapy for women with eclampsia and preeclampsia. However,
      magnesium sulfate should not be used in order to treat preterm labor.

PMID- 15567968
TI  - [The role of the semi natural cycle as option of treatment of patients with a
      poor prognosis for successful in vitro fertilization].
AB  - OBJECTIVE: To evaluate the efficacy of semi natural cycle as option of treatment
      for the patients who have a poor prognosis to controlled ovarian hyperstimulation
      (COH). PATIENTS AND METHODS: Prospective study. Sixty-six patients with an
      ovulatory cycle who presented either altered ovarian status (AOS) or implantation
      failure (IMF) and had carried out a total of 133 semi natural IVF cycles were
      included. Once follicular dominance was established, the growth of this follicule
      was controlled by administration of the GnRH antagonist with exogenous
      gonadotrophins. RESULTS: Groups AOS (n = 47) and IMF (n = 19) were similar with
      regard to oocyte pickup rate (81.2% and 81.1%), the oocyte recovery rate (61.4%
      and 64.8%) and clinical pregnancies per oocyte pickups rate (15.4% and 16.6%),
      respectively. CONCLUSIONS: The semi natural cycle appears as option of treatment
      for patients who have a poor prognosis for successful in vitro fertilization.

PMID- 15567969
TI  - [Polycythemia vera and pregnancy].
AB  - Polycythemia vera is a rare chronic myeloproliferative disease. Its exceptional
      association with pregnancy can lead to severe complications. Antithrombotic
      treatment could prevent such adverse outcome. A patient with two previous
      pregnancies complicated by preeclampsia, was treated by hydroxyurea for
      polycythemia vera. She started a new unexpected gestation without this
      myelosuppressive treatment and the pregnancy was conducted uneventfully with low
      molecular weight heparin and low dose aspirin. Thrombotic complications required
      the reintroduction of hydroxyurea. Diagnosis of polycythemia vera during
      pregnancy is a very difficult task due to physiologic changes occurring during
      gestation. Adverse outcome including severe vascular complications can be a
      preclinical phase of the disease. An adequate therapy could prevent these
      complications.

PMID- 15567970
TI  - [Unexpected discovery of a bladder tumor during a TVT operation].
AB  - With the common use of the tension-free vaginal tape (TVT) procedure, we will
      probably be facing more and more pathologies that will require a transurethral
      treatment. We report an intra-operative discovery of a bladder tumor during a
      cystoscopic TVT procedure. The tumor was easily treated by several transurethral
      resections without any consequences on the result of the TVT procedure.

PMID- 15567971
TI  - [Obstetrical practices: changing times].

PMID- 15567972
TI  - Catha edulis: a new differential in the diagnosis of pregnancy induced
      hypertension.

PMID- 15567973
TI  - Presence of morphine in rat amygdala: evidence for the mu3 opiate receptor
      subtype via nitric oxide release in limbic structures.
AB  - BACKGROUND: We have identified a novel mu opiate receptor, p3, which is expressed
      in several human tissues, is selective for opiate alkaloids, insensitive to
      opioid peptides, and also is coupled to constitutive nitric oxide release. We,
      and others, have also demonstrated the presence of opiate alkaloids as endogenous
      substances in various nerve tissues taken from mammals, man and invertebrates.
      MATERIAL/METHODS: Morphine isolation and identification was achieved by high
      pressure liquid chromatography coupled to electrochemical detection. This
      material was finally identified by nano-electrospray ionization quadruple time-of
      flight tandem mass spectrometry (Q-TOF MS/MS). Morphine's ability to release
      nitric oxide from limbic tissues was determined in real-time via an amperometric
      probe. RESULTS: We demonstrate the presence of morphine in rat brain amygdala at
      12.7 +/- 5.4 ng/g wet tissue. Morphine was able to stimulate the release of
      nitric oxide from hippocampus and amygdalar tissues in a naloxone and L-NAME
      sensitive manner. Furthermore, rat chow, incubation medium etc, did not contain
      morphine, eliminating the possibility of contamination. CONCLUSION: This finding
      provides evidence that morphine biosynthesis occurs in mammalian neural tissues.
      It also demonstrates that morphine releases nitric oxide in limbic tissues. Given
      the limbic system involvement in modulating emotion, including experiences
      related to pain perception, it appears that morphine is involved with this
      activity.

PMID- 15567974
TI  - In vitro effect of neuropeptides on ovary or celiac ganglion affects the release
      of progesterone from ovaries in the rat.
AB  - BACKGROUND: The purpose of this work was to examine the in vitro effects of three
      neuropeptides--vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and
      substance P (SP)--on the release of ovarian progesterone (Po), acting directly on
      the ovary (O) or on the celiac ganglion (CG) of rats in diestrus 1 (D1) and 2
      (D2), because in these two cycle stages neural effects have been observed on P
      release. MATERIAL/METHODS: Hemiovaries of rats in D1 and D2 were incubated with
      each neuropeptide alone and in combination with norepinephrine. Also, the CG
      superior ovarian nerve (SON)-O system was incubated with the addition of each
      neuropeptide to the CG. RESULTS: In D1 ovaries, NPY, VIP or SP, both alone and
      with norepinephrine, generally decreased the release of Po. The effect of each
      neuropeptide was modified by norepinephrine. In D2, NPY, VIP or SP, both alone
      and with norepinephrine, increased Po release. The effect of NPY and SP was
      modified by norepinephrine. In the CG-SON-O system, in D1, the addition of NPY
      and VIP alone increased Po release, while SP decreased it. In D2, the three
      neuropeptides increased Po release. CONCLUSIONS: Of the studied situations, only
      the effects of NPY and VIP on the CG during D1 mirror the changes of progesterone
      in blood during the rat estrous cycle. These effects are in agreement with others
      obtained by intracerebroventricular injection of epinephrine, suggesting that
      these neuropeptides might be released on CG after this injection and produce
      increased progesterone in blood.

PMID- 15567975
TI  - The effect of TGFbeta1 on the expression and phosphorylation of key cell-cycle
      regulators in malignant B cells.
AB  - BACKGROUND: Transforming growth factor beta1 (TGFbeta1) induces growth arrest in
      many cell types, including B lymphocytes. The inhibitory action of TGFbeta1 is
      mediated by the deactivation of kinase complexes. The cell-cycle engine is
      tightly controlled by cyclin-dependent kinase (cdk) inhibitors, which mediate
      extracellular negative signals, resulting in cell-cycle arrest at different G1
      points. MATERIAL/METHODS: Our experimental DoHH2 cell line model was derived from
      a patient with malignant non-Hodgkin's lymphoma (NHL) of follicular origin. We
      examined the effect of TGFbeta1 on the expression and phosphorylation of key cell
      cycle regulators by immunoprecipitation and immunoblotting. RESULTS: After 48
      hours of TGFbeta1 (10 ng/ml) treatment, a significantly increased number of DoHH2
      cells was retained in G0/G1 phase. Our results showed the inhibitory action was
      associated with hypophosphorylation of pRb on serine 795 (S795) and threonine 373
      (T373). We examined the composition of the cdk complexes and the level of cdk
      inhibitors to explain the inhibitory action of TGFbeta1 on cdk activity. Western
      blotting showed that the total level of the kinase inhibitor p21 (WAF1) increased
      after TGFbetal treatment. Our results indicate that a notably high level of
      p21(WAF1) was bound to cdk4/6 due to the treatment and that the binding of
      p21(WAF1) was associated with cyclin D-cdk4/6 complex decomposition. CONCLUSIONS:
      Our investigation of the effect of TGFbetal on cell-cycle progression of a non
      Hodgkin's lymphoma cell line of follicular lymphoma subtype showed that the
      TGFbeta1-induced growth arrest of malignant B cells was associated with the
      activation of CIP/KIP family members of cdk inhibitors.

PMID- 15567976
TI  - Effects of dietary caffeine and alcohol on liver carbohydrate and fat metabolism
      in rats.
AB  - BACKGROUND: The effects of caffeine on fatty liver induced by high-fat (low
      carbohydrate) diets were examined in the presence or absence of alcohol
      consumption by rats. MATERIAL/METHODS: For periods ranging from two to twelve
      weeks, male Long-Evans rats were given alcohol-free or alcohol-containing liquid
      diets balanced for energy content, but varying in fat and carbohydrate. In
      addition, several of the groups were given 0.05% caffeine as a constituent of the
      liquid diet. At the end of the experiments, trunk blood was collected for blood
      glucose and plasma leptin, epididymal fat pads were weighed, and liver was taken
      for analysis of glycogen, glucose, and fat. RESULTS: Ethanol-containing diets
      increased liver fat and depleted liver glycogen and glucose as compared to the
      corresponding ethanol-free diets, but these effects were less severe in rats
      given high-carbohydrate diets as compared to those maintained on the high-fat
      diet. The inclusion of 0.05% caffeine in the diet increased the motor activity of
      animals with access to a running wheel, yet had no protective effect against
      ethanol-induced depletion of liver glucose and induction of fatty liver. In fact,
      caffeine appears to exacerbate the effect of ethanol to deplete liver glycogen,
      decrease epididymal fat pad weight and lower serum leptin. CONCLUSIONS: Since
      liver glycogen stores can be depleted by treatments such as caffeine which do not
      exacerbate ethanol-related liver fat accumulation, the depletion of liver
      glycogen following chronic ethanol is not the single causal determinant of the
      resulting fatty liver. Other aspects of carbohydrate metabolism, including
      accumulations of endogenous regulatory intermediates or ethanol-derived
      compounds, might be more directly influenced by chronic alcohol ingestion.

PMID- 15567977
TI  - Reassessing tumor markers in local recurrences of breast cancer: a new insight.
AB  - BACKGROUND: It is believed that a local recurrence of a primitive breast cancer
      has the same prognostic factor profile as its primary breast cancer tumor.
      MATERIAL/METHODS: We compared the immunohistochemical expressions of the tumor
      suppressor protein p53, estrogen receptor (ER), c-erbB2, and E-cadherin in 57
      primary invasive breast cancers and in their respective LRs. The McNemar test and
      the kappa index were used for statistical analysis. RESULTS: In 30 patients
      (52.6%) the expression of at least one of these markers was different between the
      primary and locally recurrent tumors. No significant difference was observed
      between variations in the positive and negative expressions in the primary tumor
      and local recurrence in cerbB2 (kappa = 0.86), E-cadherin (kappa = 0.55), and p53
      (kappa = 0.7). However, the ER presented a low kappa index (kappa = 0.26, p >
      0.05). CONCLUSIONS: ER expression should be reviewed in local recurrent breast
      cancer. This relevant change in ER expression is likely to change the current
      clinical practice in breast cancer evaluation and treatment.

PMID- 15567978
TI  - Analysis of the pharmacodynamic parameters in a model for neuromuscular block.
AB  - BACKGROUND: The study examines the roles of the pharmacodynamic parameters and of
      the assumptions underlying the pharmacokinetic-pharmacodynamic model proposed by
      Sheiner and coworkers to interpret the time course of neuromuscular block (NMB)
      produced by nondepolarizing muscle relaxants. MATERIAL/METHODS: The model of
      Sheiner et al. was modified by considering (a) a multiexponential equation for
      the time course of the relaxant's concentrations in plasma, (b) the transport of
      a hypothetical muscle relaxant from plasma to the site of action via diffusion,
      and (c) NMB as a function of the relaxant's concentration at the site of action,
      of gamma and IC50. The feasibility of obtaining reliable estimates of the PD
      parameters was evaluated for either a complete or an incomplete NMB. RESULTS: The
      results confirmed that reliable estimates of the PD parameters, i.e., of the
      transport rate constant, gamma, and IC50, may be obtained simultaneously if NMB
      is incomplete. Estimates of the same parameters obtained from a complete NMB are
      interdependent and, hence, unreliable. The assumptions in the original model of
      (i) a negligibly small amount of the relaxant in the effect compartment, (ii)
      steady state plasma concentration at half-maximal NMB, Cp(ss)(50), and (iii)
      transport of the muscle relaxant from the effect compartment to "Outside", are
      neither needed nor are justified. CONCLUSIONS: The model proposed by Sheiner et
      al. interprets well the time course of an incomplete NMB even without the three
      assumptions. The simulations suggest methods to verify independently the
      estimates for the transport rate constant and gamma.

PMID- 15567979
TI  - Indolalkylamines derivatives as antioxidant and neuroprotective agents in an
      experimental model of Parkinson's disease.
AB  - BACKGROUND: The neuroprotective effect of N-(2-propynyl)2-(5-benzyloxy
      indol)methylamine (PF 9601N), a novel MAO B inhibitor, and its metabolite FA 72
      on the human neuroblastoma SHSY5Y cell line lesioned with (300 microM) dopamine
      was assessed and compared with that of 1-deprenyl assayed at identical
      experimental conditions. MATERIAL/METHODS: Using this experimental model, PF 961N
      showed a neuroprotective effect in a dose-dependent manner, and at a
      concentration of 10 pM a 20% recovery of cell viability was observed. However,
      the metabolite FA72 assayed under the same experimental conditions showed an
      increase in cell viability of nearly 50%. In the case of l-deprenyl, a
      concentration of 100 microM was necessary to recover only 10% of cell viability.
      RESULTS: This neuroprotective effect could be explained in terms of the
      antioxidant capacity of PF 9601N. In this context, the antioxidant capacities of
      the novel series of MAO inhibitors, PF 9601N and its analogues, were evaluated by
      their inhibition of the auto-oxidation of dopamine to melanin and by the
      dichlorofluorescein and 2-deoxyribose methods. CONCLUSIONS: All of these
      compounds have the basic structure of an indole ring in common, but show
      different substituents at different positions in it. The corresponding structure
      activity relationship studies allowed us to conclude that the presence of a
      benzyloxy group, or a hydroxy or methoxy group, at position 5 of the indol ring
      enhanced these antioxidant characteristics, presenting a decreasing order of
      antioxidant activity of the primary > secondary > tertiary amines. The
      antioxidant properties of PF 9601 N would explain its neuroprotective effect
      observed in SHSY5Y cells lesioned with dopamine.

PMID- 15567980
TI  - Depressive symptoms and mortality in patients with congestive heart failure: a
      six-year follow-up study.
AB  - BACKGROUND: To evaluate the possible long-term effect of symptoms of depression
      on mortality risk among patients with congestive heart failure. MATERIAL/METHODS:
      Proportional hazard models were used to evaluate the effect of symptoms of
      depression on mortality among 119 clinically stable patients with symptomatic
      heart failure, recruited from an outpatient cardiology practice. Fifty-one deaths
      were registered during the six years of data collection, all from cardiac causes.
      RESULTS: Symptom of depression were a significant predictor of mortality
      (relative risk per 1-point increase on the depression scale, 1.05, confidence
      interval, 1.00 to 1.08; p = 0.016), controlling for the confounding effects of
      the personality trait of neuroticism, heart failure severity (proANP), gender and
      age. CONCLUSIONS: Given the long-term effect of depressive symptomatology on CHF
      mortality found in the present study, health care professionals should identify
      patients who are at risk of suffering from depression as early as possible, and
      should try to provide appropriate treatment. There is a need among CHF patients
      for studies that seek to examine whether treatment of depression reduces the risk
      of mortality.

PMID- 15567981
TI  - Early effects of smoking on the voice: a multidimensional study.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of tobacco on
      the voice in a relatively early stage of the cigarette-smoking habit (<10 years).
      MATERIAL/METHODS: A multi-parameter acoustic analysis tool, the Multi-Dimensional
      Voice Program (MDVP), was used to obtain a set of 27 parameters from sustained
      vowel phonations of 134 non-dysphonic young adults (aged 20-29) of both genders,
      including smokers and non-smokers. RESULTS: Some voice parameters were
      significantly altered in young smokers when compared with young non-smokers,
      probably as a consequence of histological changes caused by tobacco. Main
      differences were observed in Frequency Perturbation parameters (jitter, sPPQ) for
      both genders, in Fundamental Frequency parameters (Fo, Fhi, Flo) mainly in women,
      and in tremor parameters (ATRI, FTRI) in men. The number of cigarettes smoked per
      day was related to the Fundamental Frequency values in women and FTRI in men. A
      discriminant analysis correctly classified 70-75% of the subjects in each gender
      group as smokers and non-smokers. CONCLUSIONS: A combination of voice parameters
      seems to suggest a possible neurological effect of nicotine--or some other
      chemical component of tobacco--on the voice.

PMID- 15567982
TI  - Direct immunofluorescence on uninvolved, lesional and perilesional skin in
      patients with endemic pemphigus foliaceus (fogo selvagem).
AB  - BACKGROUND: Research on direct immunofluorescence in pemphigus foliaceus ("fogo
      selvagem") has been focused mainly on the study of perilesional and lesional
      skin, while little attention has been given to uninvolved skin. We analyzed the
      frequency of IgA, IgM, IgG and its subclasses (IgG1, IgG2, IgG3 and IgG4) and C3
      complement fraction deposition in intercellular spaces (ICS) and basal membrane
      zone (BMZ) in uninvolved, lesional and perilesional skin from 47 fogo selvagem
      patients. MATERIAL/METHODS: For each patient biopsies were collected from
      lesional, perilesional and uninvolved skin, and then analyzed by direct
      immunofluorescence. The panel of antibodies consisted of IgA, IgM, IgG and its
      subclasses (IgG1, IgG2, IgG3 and IgG4) and C3 complement fraction. RESULTS: The
      results showed a predominance of IgG and IgG4 deposit in all skin samples,
      followed by C3 complement fraction and IgG1 deposits. The positive response for
      IgG on uninvolved (91.48%), lesional (93.61%) and perilesional (97.87%) skin was
      similar to that found for IgG4 in the same samples: 95.74%, 95.74% and 97.87%,
      respectively. Regarding IgG1, the uninvolved skin showed lower results (14.89%)
      than the lesional (29.78%) and perilesional skin (29.78%). Concerning C3
      complement fraction, the perilesional skin showed higher results (40.42%) than
      the uninvolved and lesional skin (34.04% for both). CONCLUSIONS: The results
      suggest the importance of uninvolved skin for direct immunofluorescence in the
      diagnostics of pemphigus foliaceus. Our results suggest that any cutaneous region
      can demonstrate pemphigus antibodies by direct immunofluorescence.

PMID- 15567983
TI  - Effect of Lactobacillus casei supplementation on the effectiveness and
      tolerability of a new second-line 10-day quadruple therapy after failure of a
      first attempt to cure Helicobacter pylori infection.
AB  - BACKGROUND: Probiotics have never been used as second-line treatment in patients
      resistant to a first course of anti-H. pylori treatment. MATERIAL/METHODS: 70
      consecutive patients with persistent H. pylori infection were enrolled and
      treated with ranitidine bismuth citrate (RBC) 400 mg b.d, esomeprazole or
      pantoprazole 40 mg/day, amoxycillin 1 g t.d, tinidazole 500 mg b.d. with (group
      A) or witlhout (group B) supplementation with 750 mg daily containing 16 billion
      bacteria Lactobacillus casei subsp. casei DG. Esomeprazole or pantoprazole 40
      mg/day was administered for a further 4 weeks in cases of active peptic ulcer or
      severe gastritis detected at endoscopy. In these cases endoscopy was repeated one
      month after conclusion of therapy. The remaining patients were checked by 13C
      urea breath test. RESULTS: Sixty-six patients completed the study, 34 in group A
      and 32 in group B. One group A patient (2.85%) was excluded for protocol
      violation and one group B patient (2.85%) was lost to follow-up. 33/34 group A
      patients were H. pylori-negative [per-protocol: 97.05%, on intention-to-treat:
      94.28%]. 5/34 patients (14.7%) showed side-effects, but all of them completed the
      treatment. In group B, two patients (5.71%) showed severe side-effects and were
      withdrawn from the study. 30/32 patients were H. pylori-negative [per-protocol:
      93.75%, on intention-to-treat: 85.71% (p = n.s.)]. 11/32 patients (34.37%) showed
      side-effects, but all of them completed the study (p < 0.05). CONCLUSIONS: This
      10-day quadruple therapy obtains a high eradication rate, but probiotic
      supplementation reduces side-effects and permits a slight improvement in
      eradicating H. pylori.

PMID- 15567984
TI  - Distribution of low density lipoprotein subclasses in Macedonian children.
AB  - BACKGROUND: Current reports claim that small and dense LDL particles are more
      atherogenic than larger LDL particles. There are many studies presenting LDL
      subclass distribution in adults, but there is not enough data regarding children
      in the literature on this problem. The aim of our study was to examine LDL
      subclass distribution in healthy children in the Republic of Macedonia.
      MATERIALS/METHODS: Plasma LDL subclasses in 100 children aged 9-18 years were
      analyzed using non-denaturing polyacrilamide gradient (3-31%) gel
      electrophoresis. Conventional plasma lipid and apoprotein parameters thought to
      be related to LDL size were determined as well. RESULTS: The results obtained
      showed the prevalence of large LDL subclasses (phenotype A) in 89% of the
      children, whereas small LDL subclasses (phenotype B) were observed in 11%. The
      mean LDL size was 26.37 +/- 0.68 nm, and there was no difference between gender
      groups. No association was noted between LDL size and plasma lipid and apoprotein
      levels, age, or BMI. CONCLUSIONS: LDL size and distribution is not gender- or age
      dependent, or influenced by plasma lipid and apoprotein concentrations in
      childhood. This suggests that analysis of LDL subclass phenotype may provide
      better information on the risk of atherosclerosis development in adulthood.

PMID- 15567985
TI  - Pyruvate kinase activity in the placentas of women living in polluted and
      unpolluted environments.
AB  - BACKGROUND: It was shown earlier that in women living in a polluted environment,
      the proportion of hypotrophic newborns was greater than in the general
      population. The placentas of these women show significant histological changes.
      The authors decided to check whether the activity of pyruvate kinase (PK), a key
      enzyme in the third stage of glycolysis, changes similarly. MATERIAL/METHODS: The
      study was conducted on placentas collected from women who had lived in a polluted
      environment (Groups I and II) and those who had inhabited an unpolluted area
      (Group III) while pregnant. RESULTS: Total PK activity and the specific
      activities of its isoenzymes were measured according to the Bucher and Pfleiderer
      method. The isolation of PK isoenzymes was carried out following the previously
      described procedure. Total PK activity was lower in the placentas of women of
      Groups I and II than in those of Group III. The presence of two PK isoenzymes, M2
      and L, was demonstrated. The M2 and L isoenzymes from the placentas of Groups I
      and II had a lower specific activity than those of Group III. Only one form of
      the M2 isoenzyme and the L dephospho-isoenzyme in the placentas from Groups I and
      II was observed, while in placentas of Group III women both forms of the M2
      isoenzyme and the L phospho-isoenzyme were noted. CONCLUSIONS: It is possible
      that the presence of the two PK isoenzymes in the placenta ensures the production
      of a sufficient amount of pyruvate.

PMID- 15567986
TI  - Immunogenicity of hepatitis B vaccine in multi-transfused thalassemic patients
      with and without hepatitis C infection: a comparative study with healthy
      controls.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent in thalassemic
      patients. This may decrease serum antibody response to hepatitis B virus (HBV)
      vaccine. There is also some alteration in the immune system of multi-transfused
      thalassemic patients as a consequence of iron overload. We deduced that HCV
      infection may reduce the effectiveness of HBV vaccine in multi-transfused
      thalassemic patients. MATERIAL/METHODS: Subjects were cited and studied
      prospectively in three groups. Group 1:125 multi-transfused thalassemic patients
      with negative serum HCV antibody, Group 2:96 multi-transfused thalassemic
      patients with positive serum HCV antibody on at least 2 different occasions, and
      Group3:100 healthy subjects. Subjects in all groups had negative serum HBsAg,
      anti-HBc, and anti-HBs, and they received three 20-microg doses of recombinant
      HBV vaccine in months 0,1, and 6. The anti-HBs titer was obtained one month after
      the last dose of vaccine and was considered seroprotective if > or =10 IU/l.
      RESULTS: The seroprotection rate was 83.2% in Group 1 and 80.2% in Group 2 (P =
      0.74). It was 86% in healthy subjects, which didn't significantly differ from HCV
      positive and -negative thalassemics (P = 0.56). Moreover, the mean values of ALT
      among the responder and non-responder thalassemic patients were 55.5 +/- 41.9 and
      57.4 +/- 48.5 U/l, respectively (p = 0.802). During the vaccination periods,
      patients in all 3 groups did not show any significant adverse reactions.
      CONCLUSIONS: Our study shows that three standard doses of HBV vaccine are
      immunogenic and safe in multi-transfused thalassemic patients with or without HCV
      infection.

PMID- 15567987
TI  - Respiratory failure as a first presentation of myasthenia gravis.
AB  - BACKGROUND: Although respiratory failure commonly occurs during the course of
      myasthenia gravis (MG), it is rarely described at presentation in patients with
      previously unrecognized MG. MATERIAL/METHODS: We determined the prevalence and
      clinical characteristics of patients with respiratory failure associated with
      undiagnosed MG by review of the medical records of all patients who were
      diagnosed with MG related respiratory failure at four University hospitals.
      Respiratory failure was defined on the basis of a forced vital capacity < or =1
      liter, negative inspiratory force < or =20 cm H2O, or requirement of mechanical
      ventilation. RESULTS: Out of 51 MG patients with respiratory failure, 7(14%)
      patients had no previous diagnosis of MG. Another patient was identified after
      the review. The mean age of these 8 patients was 56 years (range 23-76 years);
      six were women. Five had previous episodes of unexplained respiratory failure. On
      initial evaluation, ocular or bulbar signs were present in 7 patients. The
      diagnosis of MG was made by edrophonium test (n=3), edrophonium test with
      positive acetylcholine antibody levels or repetitive nerve stimulation (n=2),
      repetitive nerve stimulation with positive acetylcholine antibody levels (n=2),
      and positive acetylcholine antibody levels alone (n=1). Seven patients required
      mechanical ventilation. Plasma exchange (n=7) or intravenous immunoglobulins
      (n=1) resulted in successful extubation or resolution of symptoms in all
      patients. CONCLUSIONS: Respiratory failure can occur at presentation in MG. A
      high index of suspicion should be maintained in patients with previous history of
      unexplained respiratory failures.

PMID- 15567988
TI  - Autonomic dysreflexia manifested by severe hypertension.
AB  - BACKGROUND: Autonomic dysreflexia (AD) is a sudden and exaggerated autonomic
      response to stimuli in patients with spinal cord injuries or dysfunction above
      the splanchnic sympathetic outflow (T5-T6). Hypertension is a relatively common
      manifestation of AD. CASE REPORT: We describe a case of a young man with T4-T6
      spinal cord tumor who developed severe hypertension before any other clinical
      feature of AD, leading to a subsequent clinical evaluation and the correct
      diagnosis. Treatment with labetalol was only partially successful in controlling
      the elevated blood pressure. Hypertension resolved immediately after bladder
      decompression. CONCLUSIONS: AD manifested by severe hypertension is uncommon.
      Bladder decompression appears to be safe and effective for management of
      hypertension in patients with AD.

PMID- 15567989
TI  - A case report of Noonan's syndrome with pulmonary valvar stenosis and coronary
      aneurysms.
AB  - BACKGROUND: Noonan syndrome is a rare disease, mainly presenting with
      malformations such as dysplasia and stenosis of the pulmonary valve, atrial
      septal defect and a typical pattern of hypertrophic cardiomyopathy. We report a
      case of Noonan syndrome with giant coronary aneurysms. CASE REPORT: A young woman
      with the phenotypic characteristics of Noonan's syndrome presented with severe
      pulmonary stenosis and giant coronary aneurysms. Cross sectional echocardiography
      showed valvar and subvalvar pulmonary stenosis. The valve itself was thickened
      and dysplastic, a characteristic that is typical of Noonan's syndrome. In
      addition to the usual abnormalities of the pulmonary valve and the ventricular
      myocardium, the patient showed a wide spectrum of previously unreported coronary
      aneurysms. CONCLUSIONS: These additional findings support the hypothesis that a
      vasculitic process has been superimposed on the connective tissue defect
      associated with Noonan's syndrome. Furthermore, since the pathogenesis of the
      condition remains unclear, this case stresses the need to look carefully for
      abnormalities co-expressed in Noonan's syndrome.

PMID- 15567990
TI  - Can perinatal supplementation of long-chain polyunsaturated fatty acids prevents
      schizophrenia in adult life?
AB  - It is suggested that perinatal supplementation of long-chain polyunsaturated
      fatty acids (LCPUFAs) especially; eicosapentaenoic and docosahexaenoic acids
      prevent schizophrenia in the adult. I propose that schizophrenia could be a low
      grade systemic inflammatory disease with its origins in the perinatal period,
      probably triggered by maternal infection in a genetically susceptible individual
      that leads to excess production of pro-inflammatory cytokines both in the mother
      and the fetus. These cytokines, in turn, induce damage to the fetal neurons
      leading to the adult onset of schizophrenia. I suggest that maternal infection
      perse interferes with the metabolism of essential fatty acids (EFAs) resulting in
      deficiency of LCPUFAs that are known to have neuroprotective action.
      Alternatively, decreased formation of LCPUFAs as a result of decreased activity
      of D6 and D5 desaturases (due to prematurity) can result in neuronal damage due
      to the absence/decrease in the neuroprotective LCPUFAs. This is supported by the
      observation that LCPUFAs suppress the production of pro-inflammatory cytokines,
      have anti-inflammatory and neuroprotective actions. Furthermore, LCPUFAs are
      essential for brain growth and development. If this hypothesis is true, it
      implies that perinatal supplementation of appropriate amounts of LCPUFAs in the
      right combination is helpful in the prevention of schizophrenia in adult life.

PMID- 15567991
TI  - ADMET biosensors: up-to-date issues and strategies.
AB  - This insight review introduces the new concepts, theories, technology,
      instruments, frontier issues, and key strategies of ADMET (absorption,
      distribution, metabolism, elimination, and toxicity) biosensors, from the fermi
      to the quantum levels. Information about ADMET, originating from one author's
      invention, a patented pharmacotherapy for rescuing cardio-cerebral vascular
      stunning and regulating vascular endothelial growth-factor signaling at the post
      genomic level, can be detected by a new generation of ADMET biosensor. This is a
      single-cell/single-molecule field-effect transistor (FET) hybrid system, where
      single molecules or single cells are assembled at the FET surface in a high
      density array manner via complementary metal-oxide-semiconductor (CMOS)
      compatible technologies. Within a given nanometer distance, ADMET-mediated
      oxidation-reduction (redox) potentials, electrochemistry responses, and electron
      transfer processes can be simultaneously and directly probed by the gates of
      field-effect transistor arrays. The nanometer details of the functional coupling
      principles and characterization technologies of DNA single-molecule/single-cell
      FETs, as well as the design of lab-on-a-chip instruments, are indicated. Four
      frontier issues and key strategies are elucidated in detail. This can lead to
      innovative technology for high-throughout screening of labs-on-chips to resolve
      the pharmaceutical industry's current bottleneck via novel, FET-based drug
      discovery and single-molecule/single-cell screening methods, which can bring
      about a pharmaceutical industry revolution in the 21st century.

PMID- 15567992
TI  - Views on neurodegeneration as a basis for neuroprotective strategies.
AB  - Evidence is presented to demonstrate neurodegenerative processes in Parkinson's
      disease which are interconnected and may be synergistic in a way that they self
      perpetuate progression. Free iron plays a predominant role, because it may be
      continuously and unlimitedly taken up through a disturbed blood-brain-barrier.
      Iron's toxic action is at both neuronal and glial sites. Loss of tyrosine
      hydroxylase protein and activity and fibrillation of alpha-synuclein connected
      with disturbed proteasomal protein breakdown contribute to cell death, as are
      changes in neuromelanin concentration and binding affinity, e.g. for iron. The
      interplay of genetic disturbances and neuronal and glial pathological processes
      involving the functioning of the blood-brain barrier, eventually initiated via an
      ascending toxic process, is the key for attacking vulnerable catecholaminergic
      neurons such as those in the substantia nigra and locus coeruleus.
      Neuroprotective therapeutic strategies are difficult to achieve because of the
      immanent complexity of cell death cascades.

PMID- 15567993
TI  - Neural redox stress and remodeling in metabolic syndrome, type 2 diabetes
      mellitus, and diabetic neuropathy.
AB  - Diabetic polyneuropathy (DPN) is the most common complication of diabetes and may
      frequently be the presenting symptom in type 2 diabetes mellitus (T2DM).
      Metabolic syndrome and T2DM are associated with multiple metabolic toxicities.
      These substrate toxicities support the formation of reactive oxygen species
      (ROS), which are so damaging to cells, tissues and organs and play an important
      role in the development of multiple diabetic complications. The importance of
      redox stress (ROS) and their effect on the neuronal unit are discussed. There are
      at least 5 major pathways involved in the development of DPN: metabolic,
      vascular, immunologic-autoimmune, neurohormonal growth factor deficiency, and
      extracellular matrix neuronal unit remodeling. Each of these five pathways are
      reviewed and related to neural redox stress and the role of ROS. The
      identification of the toxic substrates (A-FLIGHT acronym), earlier diagnosis of
      T2DM at the stage of impaired glucose tolerance or impaired fasting glucose, and
      aggressive global risk reduction with the use of a simple RAAS acronym will
      assist the clinician in slowing the natural progressive history, and possibly
      preventing the complications associated with DPN. The pain, foot ulceration, limb
      loss, organ dysfunction, and the associated morbidity and financial burden all
      contribute to the need for a better understanding of DPN and the role of redox
      stress and global risk reduction.

PMID- 15567994
TI  - The role of inflammation in atherothrombosis: current and future strategies of
      medical treatment.
AB  - Atherosclerosis is a pathological process caused by vascular remodeling. It
      symbolizes one of the major causes for morbidity and mortality in the western
      world. The causes for these vascular problems are manifold and different
      etiologies have been discussed. Since the 1980s the role of chronic inflammation
      has been considered and is now confirmed by many studies and experimental data.
      Several inflammatory pathways have been shown to participate in the
      atherosclerotic process. Different markers for inflammation have been found to
      predict the future risk for developing cardiovascular disease. Among these, high
      sensitivity C-reactive protein has been the most extensively validated. Newer
      markers such as CD40 ligand appear also to provide important information
      regarding risk stratification. Medications have been found to lower levels of
      inflammatory markers and perhaps decrease the associated clinical risk. Statins
      particularly appear to have anti-inflammatory mediated benefits, though other
      classes of drugs are also being evaluated. Lipid-lowering therapy in general has
      been found to be associated with reductions in inflammatory markers.
      Antithrombotic therapy, such as intravenous glycoprotein lIb/IIIa inhibitors and
      clopidogrel, has also been demonstrated to reduce inflammatory marker release.
      Peroxisome proliferator-activated receptor agonists are being evaluated for
      possible roles in targeting arterial inflammation. Angiotensin-converting enzyme
      inhibitors may also have anti-inflammatory properties. In this article we review
      the existing data in the inflammatory model of atherosclerosis. Furthermore, we
      discuss the prognostic value of different inflammatory markers and the potential
      benefit of anti-inflammatory therapies in cardiovascular disease.

PMID- 15567995
TI  - Soluble tumor-associated antigens in cancer detection, prevention and therapy.
AB  - Soluble tumor-associated antigens (sTAA) with molecular mass of 66 and 51 kDa
      isolated from the serum of cancer patients was shown can be used for cancer
      detection, prevention and therapy. CANCER DETECTION: Cancer progression is
      reflected in the relationship between p66 and p51 compared to healthy people or
      to patients with non-cancer diseases. The method was shown to be highly sensitive
      (92 to 96%) and moderate specific (42 to 65%) for the detection of different
      types of cancer, such as of the colon, uterus, ovary, and breast, as well as
      melanoma. CANCER PREVENTION AND THERAPY: sTAA have both tumor-preventive and
      tumor-suppressive effects on chemically induced cancers of the colon, skin and
      mammary glands in rats and mice. sTAA promote suppression of rat mammary tumors
      by different anticancer drugs, such as cyclophosphamide, tamoxifen and 5
      fluorouracil, and decrease the drug's toxic side-effects. This effect was shown
      to be connected with activation of the host's immune system, especially those
      which is responsible for activity of T and B lymphocytes. CONCLUSIONS: We propose
      the follow-up after cancer patients in order to verify earlier as soon as
      possible recurrent cancer and perform preventive therapy of cancer suspect
      patients with their own sTAA as a kind of autoimmunotherapy. Moreover, in
      combination with anticancer drugs, sTAA may serve as a new tool in prevention of
      toxic side-effects of chemotherapy.

PMID- 15567996
TI  - Genetic aspects of chronic pancreatitis.
AB  - The classical feature of hereditary pancreatitis (HP) is characterized by
      recurrent episodes of acute pancreatitis or a priori chronic pancreatitis in
      several members of one family. In 1996, the identification of the first HP
      associated mutation in the cationic trypsinogen gene provided a breakthrough in
      our understanding of the pathogenesis of chronic pancreatitis. In the following
      years, several different mutations in the same gene have been found in a large
      number of investigated families. Most intriguing, HP patients have a more than 50
      fold increased risk of pancreatic ductal cancer in comparison with expected
      pancreatic cancers in the general population. Variants of the major
      intrapancreatic trypsin antagonist SPINK1 have implications for more common forms
      of chronic pancreatitis. Research has focussed on the SPINK1-N34S-mutation, which
      is closely associated with tropical, alcoholic, or "idiopathic" chronic
      pancreatitis. Chronic pancreatitis represents a variable part of the cystic
      fibrosis syndrome, which is caused by mutations in the gene coding for the cystic
      fibrosis transmembrane conductance regulator (CFTR). Several groups have reported
      an increased prevalence of CFTR mutations in patients with chronic pancreatitis
      of different etiology. In this review, we summarize interesting clinical and
      biochemical features of genetic variants in these genes which are associated with
      chronic pancreatitis.

PMID- 15567997
TI  - Cardiovascular protection with ace inhibitors--more HOPE for EUROPA?
AB  - BACKGROUND: Treatment with angiotensin converting enzyme (ACE) inhibitors reduces
      mortality and morbidity among patients with heart failure, left-ventricular
      dysfunction after myocardial infarction and with hypertension. In addition, they
      have been shown to slow the progression of chronic kidney disease and reduce the
      recurrence of stroke and vascular events. MATERIAL/METHODS: There has been an
      enormous interest in the potential cardioprotective effects of ACE inhibitors.
      This principle has been assessed in two landmark double blind placebo controlled
      clinical trials, HOPE and EUROPA. This article seeks to review and compare the
      important findings of these two clinical studies. RESULTS: In the HOPE study,
      ramipril once daily produced a 22% reduction in the primary composite endpoint of
      myocardial infarction, stroke, or cardiovascular death (P < 0.001) among an older
      cohort (>55 years) of patients at high risk of future cardiovascular
      complications. The EUROPA study assessed the effects of the ACE inhibitor
      perindopril in a larger group of lower risk patients with established stable
      cardiovascular disease. In EUROPA, once daily treatment with perindopril lead to
      a significant 20% relative risk reduction in the combined primary endpoint
      (cardiovascular mortality, non-fatal myocardial infarction, and resuscitated
      cardiac arrest; p = 0.0003). CONCLUSIONS: HOPE and EUROPA provide compelling
      evidence to suggest that all patients with evidence of stable cardiovascular
      disease or diabetes (plus one additional risk factor) should be treated with an
      ACE inhibitor.

PMID- 15567998
TI  - [Radiological technology and medical ethics].

PMID- 15567999
TI  - [Echocardiography].

PMID- 15568000
TI  - [Brief explanation of discussion by Committee on Health Information Network
      Infrastructure].

PMID- 15568001
TI  - [ Articles on the 20th Anniversary of the short-term studying abroad program in
      JSRT].

PMID- 15568002
TI  - [Action of medical facilities on the revised pharmaceutical affairs law -part 1
      ].

PMID- 15568003
TI  - [Distinguishing between occluded and low-flow vessels with PROPELLER DWI
      sequence: a phantom study].
AB  - PURPOSE: To evaluate the ability of periodically rotated overlapping parallel
      lines with enhanced reconstruction diffusion-weighted imaging (PROPELLER DWI) to
      distinguish between vessel occlusion and slow flow. MATERIALS AND METHODS: Using
      a flow phantom with various velocities (1.37 to 11.1 cm/s), the signal-intensity
      ratios of the phantom, with the intensity of no flow as baseline, were measured
      using the following imaging sequences: PROPELLER DWI, spin-echo T1-weighted
      imaging (SE T1WI), fast-spin-echo T2-weighted imaging (FSE T2WI), two-dimensional
      phase-contrast imaging (2D PC), and two-dimensional time-of-flight imaging (2D
      TOF). The b-factor of PROPELLER DWI was varied from 0 to 1000 s/mm(2). The
      velocity encoding of 2D PC was varied from 2 to 30 cm/s. RESULTS: At the lowest
      flow velocity (1.37 cm/s) , the signal-intensity ratio was 0.0075 for PROPELLER
      DWI (b-factor=1000 s/mm(2)), 1.8 for SE T1WI, 0.67 for FSE T2WI, 11 for 2D PC
      (velocity encoding=2 cm/s), and 1.4 for 2D TOF. The signal-intensity ratio was
      smallest for PROPELLER DWI, even when the reciprocals of the signal-intensity
      ratio of 2D PC or 2D TOF were considered. CONCLUSION: The results indicate that
      PROPELLER DWI provides the best signal intensity-ratio between vessel occlusion
      and slow flow. Although DWI with single-shot echo-planar imaging (EPI) or multi
      shot EPI may have similarly high sensitivity for slow flow, these sequences do
      not have high spatial resolution or robustness to susceptibility artifacts.
      PROPELLER DWI would be a better choice for distinguishing between occluded and
      low-velocity arteries in the skull base or parasellar regions.

PMID- 15568004
TI  - [Dose estimation with CTDI100, air in computed tomography].
AB  - Although the principal dosimetric quantity in computed tomography (CT) can be
      assessed using a pencil ionization chamber with an active length of 100 mm,
      standard CT dosimetry phantoms of polymethylmethacrylate (PMMA) , and plates of
      aluminum, most facilities do not possess the requisites. We present a practical
      method of estimating CTDI(100, c), CTDI(100, p) and the half-value layer (HVL)
      from CTDI(100, air), which is measured parallel with the axis of rotation of the
      scanner to free-in-air. The three data chosen for this method of estimation were
      as follows: 1) the relation of HVL to CTDI(100, air) per radiographic exposure
      (mAs); 2) the relation of HVL to CTDI(100, c) per CTDI(100, air); 3) the relation
      of HVL to CTDI(100, p) per CTDI(100, air). The data were based on the measured
      values of six CT scanners, so as to avoid dependence on the technical
      characteristics of a specific manufacturer. The estimated value has a possible
      maximum uncertainty of 20%, although this method of estimation is practical for
      dose assessment.

PMID- 15568005
TI  - [Accuracy of measurement of radiochromic film density for high-energy X-rays].
AB  - Radiochromic film (RC-film) is of great interest as a film-type dosimeter for
      radiation oncology applications. We present a two-dimensional image-based
      evaluation of the measurement accuracy of a commercial RC-film product
      (Gafchromic MD-55-2 film, ISP TECHNOLOGIES, Inc.) by using a commercial Laser
      Densitometer (Model 1710, Computerized Medical Systems, Inc.) as an optical
      density imaging system. The coefficient of variation of the density (pixel-value)
      in one sample was approximately 3% to 11% at 3 Gy or less, and 3% or less at 4 to
      60 Gy. Although the coefficient of variation between three samples at the same
      dose was about 14% at 1 Gy, it decreased as the dose increased, reaching several
      percent. In 1 to 6 Gy samples, geometric imaging artifacts [interference (moire)
      patterns] were observed, and it was found that scan-sampling pitch influenced the
      accuracy of measurement of the density of the sample. To improve the accuracy of
      density measurement, sufficient knowledge about characteristic features of the
      density measuring system is essential.

PMID- 15568006
TI  - [Accuracy of contrast-to-noise ratio measurement for magnetic resonance clinical
      images].
AB  - The contrast-to-noise ratio (CNR) is often used to evaluate magnetic resonance
      images, because it has two components, contrast and SNR, and indicates the
      detectability of clinical lesions. Two methods (using a phantom and using
      clinical images) are employed to measure CNR. In addition, there are some methods
      of measurement that use clinical images. In this report, the accuracy of
      measurement and correlation for signal detectability were evaluated in four
      methods of measuring CNR using clinical images. The results indicated that the
      inter-tissue method using an air signal provided good accuracy and was consistent
      with signal detectability using observer performance. In addition, a small region
      of interest (ROI) was better suited as the target for CNR measurement using
      clinical images.

PMID- 15568007
TI  - [Measurement of scatter radiation on MDCT equipment using an OSL dosimeter].
AB  - The recent introduction of multi-detector row computed tomography (MDCT) has made
      it possible to scan the entire abdomen within approximately 10 sec in procedures
      such as interventional radiology computed tomography (IVRCT), which are
      associated with operator exposure. Therefore, anxious patients and patients who
      are not able to remain still can be examined with an assistant. In the present
      study, radiation exposure to the assistant was estimated, and the distribution of
      scattered radiation near the gantry was measured using an optically stimulated
      luminescence (OSL) dosimeter. Simultaneous measurements were obtained using a
      direction storage (DIS) dosimeter for reference. The maximum value of 1.47 mSv
      per examination was obtained at the point closest to the gantry's center (50 cm
      from the center at a height of 150 cm above the floor) . In addition, scattered
      radiation decreased as the measurement point was moved further from the gantry's
      center, falling below the limit of detection (0.1 mSv or less) at 200 cm and at
      the sides of the gantry. OSL dosimeters are also employed as personal dosimeters,
      permitting reliable values to be obtained easily. They were found to be an
      effective tool for the measurement of scattered radiation, as in the present
      study, helping to provide better understanding of the distribution of scattered
      radiation within the CT room.

PMID- 15568008
TI  - [Effect of school education on students' perception of radiation].
AB  - There is a strong tendency in Japan to perceive even the smallest amount of
      radiation or radioactivity as dangerous or detrimental. An investigation was done
      to identify the age at which this perception is formed. It was found that the
      perception was initially formed during elementary school, especially when the
      description of an atomic bomb was given during the history course, which is part
      of the sociology curriculum. The description in the sociology textbook emphasizes
      the damage produced by radiation. In contrast, the textbook has few descriptions
      of the positive uses of radiation. The perception, formed in elementary school,
      of radiation as something dangerous and detrimental remains vivid until
      adolescence. The only textbook to correctly describe the benefits of radiation
      was a high school physics textbook. However, only 30% of high school students
      take physics. The system of selecting science subjects in high school is
      preventing students from obtaining a correct understanding of radiation. Little
      improvement can be found in the latest textbook published following the 2002
      governmental guidelines for education.

PMID- 15568009
TI  - [Evaluation of optimized injection dose and acquisition time using body mass
      index for three-dimensional whole-body FDG-PET].
AB  - OBJECTIVE: The standardized uptake value (SUV) is a relative measure of tracer
      uptake in tissue used in (18)F-FDG PET. However, the quality of ordered subset
      expectation maximization (OS-EM) images is sensitive to the number of iterations,
      because a large number of iterations leads to images with checkerboard noise. The
      main advantage of data acquisition in the three-dimensional (3D) mode is the high
      sensitivity to better exploit the intrinsic spatial resolution and the lower
      injection dose given to patients. In the 3D mode, the scatter fraction is higher,
      and, for a given administered dose, the random fraction is higher than that in
      the two-dimensional mode, which implies that correction methods need to be more
      accurate. Moreover, in clinical oncology (18)F-FDG PET studies, patients have a
      wide variety of body shapes and sizes, which may impact image statistics.
      Consequently, it is necessary to make constant the acquisition (true) counts. The
      purpose of this study was to optimize injection dose and acquisition time in
      consideration of body mass index (BMI) for 3D whole-body (18)F-FDG PET. METHODS:
      A dedicated PET scanner, SIEMENS ECAT EXACT HR(+), was used to scan images of
      clinical data. The injection dose for BMI of <14-19, 19-22, 22-25, and 25<
      (kg/m(2)) were, 92.5 MBq, 111.0 MBq, 129.5 MBq, and 148.0 MBq, respectively. The
      emission scan time per bed position for BMI of <14-19, 19-22, 22-25, and >25
      (kg/m(2)) were, 120, 120, 180, and 240 sec, respectively. A total of 20 patient
      subjects were evaluated as to true counts per bin (T/bin) of sinogram data and
      measured activity concentrations for the region of interest in the liver section.
      RESULTS: T/bin was stable using an optimized protocol that took into
      consideration the BMI for any type of body morphology. The overall coefficient of
      variation was 7.27% for radioactivity concentration. Additionally, Gaussian
      filtering (8 mm FWHM) after reconstruction by the OS-EM method provided stable
      SUV values even when the iteration number was increased 30 times over.
      CONCLUSION: Optimization of injection dose and acquisition time indicated that
      BMI was a clinically useful acquisition protocol for 3D whole-body (18)F-FDG PET.

PMID- 15568010
TI  - [Evaluation of image quality in mammographic film with the extended process].
AB  - This report deals with the image quality of film used in mammography in terms of
      changing the processing time of the film and reducing the radiation dose. We
      initially performed phantom experiments to investigate the extended process that
      could provide high image quality of the film. We then measured silver grain sizes
      using an optical microscope to investigate processing time, so that silver grains
      would not be coarse during the extended process. It was found that micro
      calcifications could be clearly detected by the extended process by using a lower
      radiation dose and that the extended process did not affect coarsening of the
      silver grains.

PMID- 15568011
TI  - [Imaging characteristics of PROPELLER T2-weighted imaging].
AB  - As the PROPELLER sequence is a combination of the radial scan and fast-spin-echo
      (FSE) sequence, it can be considered an FSE sequence with a motion correlation.
      However, there are some differences between PROPELLER and FSE owing to
      differences in k-space trajectory. We clarified the imaging characteristics of
      PROPELLER T2-weighted imaging (T2WI) for different parameters in comparison with
      usual FSE T2WI. When the same parameters were used, PROPELLER T2WI showed a
      higher signal-to-noise ratio (SNR) and lower spatial resolution than usual FSE.
      Effective echo time (TE) changed with different echo train lengths (ETL) or
      different bandwidths on PROPELLER, and imaging contrast changed accordingly to be
      more effective.

PMID- 15568012
TI  - [Method for estimating 4 MV X-ray irregular field dose using the collimator
      scatter factor (Sc) and phantom scatter factor (Sp)].
AB  - Calculation of in-air or in-water dose for 4 MV X-ray irregular fields could be
      accurately performed using the collimator scatter factor (S(c)) and phantom
      scatter factor (S(p)) concepts. It has been revealed that the equivalent square
      field for a multi-leaf collimator (MLC) irregular field can be evaluated
      accurately by using the S(p)-Clarkson or S(c)-Clarkson integration method;
      however, the S(c)-Clarkson integration method is more straightforward because the
      S(c) factor expresses the in-air X-ray output factor. It has been found that when
      the MLC field is relatively much smaller than the main collimator field, the Sc
      factor can be accurately evaluated by introducing the small segment correction
      (SSC) factor (except for the case in which the MLC field is less than 1 x 1
      cm(2)). It has also been found that both the S(p) factor and the tissue-phantom
      ratio (TPR) can be precisely evaluated by introducing the F(MLC) factor in cases
      in which the ratio of the MLC equivalent square field side to the main collimator
      equivalent square field side is less than about 0.7.

PMID- 15568013
TI  - [Accuracy of absorbed dose calculation and measurement of scatter factors with
      different depth of mini-phantoms using a pinpoint ionization chamber].
AB  - The output factor of high-energy X-ray machines varies with collimation.
      According to Khan's theory, collimator and phantom scatter factors contribute to
      total scatter factor. For precise X-ray irradiation, the two factors need to be
      taken into consideration. To obtain proper factors, we made two original
      polystyrene cylindrical mini-phantoms. These phantoms are both 4 cm in diameter
      and have a pinpoint ion chamber placed at a depth of 5 cm and 10 cm,
      respectively. Using a 6 MV X-ray machine, collimator scatter factors were
      calculated for various field arrangements (i.e., field sizes ranging from 4 cm x
      4 cm to 40 cm x 40 cm at isocenter). To determine if calculated values were
      appropriate, we measured point doses of 20 X-ray irradiation patterns using a
      Farmer-type ion chamber with a water equivalent phantom at depths of 5 cm and 10
      cm, respectively. Two hundred MUs were irradiated to the above-mentioned depths
      for each field. Based on the measured doses, variations were obtained for four
      calculation methods. Accounting for 1) secondary collimator (jaw) setting, 2)
      blocked field (multi-leaf collimator) setting, 3) Khan's theory using a 5 cm mini
      phantom, and 4) Khan's theory using a 10 cm mini-phantom. Dose variations in each
      method of calculation were as follows: 1) +0.3 to +10.2% (mean, +2.0 to +3.2%) ,
      2) -2.3 to 0.0% (mean, -0.8 to -0.6%), 3) 0.0 to +1.5% (mean, +0.1 to +0.3%), 4)
      0.0 to +1.4% (mean, -0.1 to +0.1%).

PMID- 15568014
TI  - Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation.
AB  - ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network
      by forming ligand-induced heterodimers with several growth factor receptors of
      the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not
      other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB
      network extends beyond regulation of protein stability. The capacity of ErbB-2 to
      recruit ligand-bound receptors into active heterodimers is limited by Hsp90,
      which is dissociated from ErbB-2 following ligand-induced heterodimerization. We
      show that Hsp90 binds a specific loop within the kinase domain of ErbB-2, thereby
      restraining heterodimer formation and catalytic function. These results define a
      role for Hsp90 as a molecular switch regulating the ErbB signalling network by
      limiting formation of ErbB-2-centred receptor complexes.

PMID- 15568015
TI  - Electron and atomic force microscopy of the trimeric ammonium transporter AmtB.
AB  - Escherichia coli AmtB is an archetypal member of the ammonium transporter (Amt)
      family, a family of proteins that are conserved in all domains of life.
      Reconstitution of AmtB in the presence of lipids produced large, ordered two
      dimensional crystals. From these, a 12 A resolution projection map was determined
      by cryoelectron microscopy, and high-resolution topographs were acquired using
      atomic force microscopy. Both techniques showed the trimeric structure of AmtB in
      which each monomer seems to have a pseudo-two-fold symmetry. This arrangement is
      likely to represent the in vivo structure. This work provides the first views of
      the structure of any member of the Amt family.

PMID- 15568016
TI  - NMR structure of the bovine prion protein isolated from healthy calf brains.
AB  - NMR structures of recombinant prion proteins from various species expressed in
      Escherichia coli have been solved during the past years, but the fundamental
      question of the relevancy of these data relative to the naturally occurring forms
      of the prion protein has not been directly addressed. Here, we present a
      comparison of the cellular form of the bovine prion protein isolated and purified
      from healthy calf brains without use of detergents, so that it contains the two
      carbohydrate moieties and the part of the GPI anchor that is maintained after
      enzymatic cleavage of the glycerolipid moiety, with the recombinant bovine prion
      protein expressed in E. coli. We show by circular dichroism and (1)H-NMR
      spectroscopy that the three-dimensional structure and the thermal stability of
      the natural glycoprotein and the recombinant polypeptide are essentially
      identical. This result indicates possible functional roles of the glycosylation
      of prion proteins in healthy organisms, and provides a platform and validation
      for future work on the structural biology of prion proteins, which will have to
      rely primarily on the use of recombinant polypeptides.

PMID- 15568017
TI  - Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins.
AB  - Select members of the Wnt family of secreted glycoproteins have been implicated
      in inducing the myogenic determinant genes Pax3, MyoD and Myf5 during mammalian
      embryogenesis, but the mechanism of induction has not been defined. We describe
      an unexpected role for protein kinase A (PKA) signalling via CREB in this
      induction. Using a combination of in vitro explant assays, mutant analysis and
      gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl
      cyclase signalling via PKA and its target transcription factor CREB are required
      for Wnt-directed myogenic gene expression. Wnt proteins can also stimulate CREB
      mediated transcription, providing evidence for a Wnt signalling pathway involving
      PKA and CREB. Our findings raise the possibility that PKA/CREB signalling may
      also contribute to other Wnt-regulated processes in embryonic patterning, stem
      cell renewal and cancer.

PMID- 15568018
TI  - Negative feedback inhibition of HIV-1 by TAT-inducible expression of siRNA.
AB  - Here we demonstrate that an inducible anti-HIV short hairpin RNA (shRNA)
      expressed from a Pol II promoter inhibits HIV-1 gene expression in mammalian
      cells. Our strategy is based on a promoter system in which the HIV-1 LTR is fused
      to the Drosophila hsp70 minimal heat shock promoter. This system is inducible by
      HIV-1 TAT, which functions in a negative feedback loop to activate transcription
      of an shRNA directed against HIV-1 rev. Upon induction the shRNA is processed to
      an siRNA that guides inhibition of HIV replication in cultured T-lymphocytes and
      hematopoietic stem cell-derived monocytes. The fusion promoter system may be
      safer than drug-inducible systems for shRNA-mediated gene therapy against HIV as
      the shRNAs are only expressed following HIV infection.

PMID- 15568019
TI  - Generation of a synthetic lymphoid tissue-like organoid in mice.
AB  - Stromal cells play an important role in the formation of the normal organized
      microarchitecture of secondary lymphoid organs. Here we demonstrate that a tissue
      engineered, lymphoid tissue-like organoid, which was constructed by
      transplantation of stromal cells embedded in biocompatible scaffolds into the
      renal subcapsular space in mice, had an organized tissue structure similar to
      secondary lymphoid organs. This organoid contained compartmentalized B-cell and T
      cell clusters, high endothelial venule-like vessels, germinal centers and
      follicular dendritic cell networks. Furthermore, the organoid was transplantable
      to naive normal or severe combined immunodeficiency (SCID) mice, and antigen
      specific, IgG-isotype antibody formation could be induced soon after intravenous
      administration of the antigen. This simplified system of lymphoid tissue-like
      organoid construction will facilitate analyses of cell-cell interactions required
      for development of secondary lymphoid organs and efficient induction of adaptive
      immune responses, and may have possible applications in the treatment of immune
      deficiency.

PMID- 15568020
TI  - Baculovirus expression system for heterologous multiprotein complexes.
AB  - The discovery of large multiprotein complexes in cells has increased the demand
      for improved heterologous protein production techniques to study their molecular
      structure and function. Here we describe MultiBac, a simple and versatile system
      for generating recombinant baculovirus DNA to express protein complexes
      comprising many subunits. Our method uses transfer vectors containing a
      multiplication module that can be nested to facilitate assembly of polycistronic
      expression cassettes, thereby minimizing requirements for unique restriction
      sites. The transfer vectors access a modified baculovirus DNA through Cre-loxP
      site-specific recombination or Tn7 transposition. This baculovirus has improved
      protein expression characteristics because specific viral genes have been
      eliminated. Gene insertion reactions are carried out in Escherichia coli either
      sequentially or concurrently in a rapid, one-step procedure. Our system is useful
      for both recombinant multiprotein production and multigene transfer applications.

PMID- 15568021
TI  - Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF
      in a rat model of ALS.
AB  - Neurotrophin treatment has so far failed to prolong the survival of individuals
      affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron
      degenerative disorder. Here we show that intracerebroventricular (i.c.v.)
      delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A)
      rat model of ALS delays onset of paralysis by 17 d, improves motor performance
      and prolongs survival by 22 d, representing the largest effects in animal models
      of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v.
      delivery of Vegf is particularly effective in rats with the most severe form of
      ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons
      in vivo, because neuronal expression of a transgene expressing the Vegf receptor
      prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is
      anterogradely transported and preserves neuromuscular junctions in SOD1(G93A)
      rats. Our findings in preclinical rodent models of ALS may have implications for
      treatment of neurodegenerative disease in general.

PMID- 15568022
TI  - Protection of p27(Kip1) mRNA by quaking RNA binding proteins promotes
      oligodendrocyte differentiation.
AB  - The quaking (Qk) locus expresses a family of RNA binding proteins, and the
      expression of several alternatively spliced isoforms coincides with the
      development of oligodendrocytes and the onset of myelination. Quaking viable
      (Qk(v)) mice harboring an autosomal recessive mutation in this locus have
      uncompacted myelin in the central nervous system owing to the inability of
      oligodendrocytes to properly mature. Here we show that the expression of two QKI
      isoforms, absent from oligodendrocytes of Qk(v) mice, induces cell cycle arrest
      of primary rat oligodendrocyte progenitor cells and differentiation into
      oligodendrocytes. Injection of retroviruses expressing QKI into the telencephalon
      of mouse embryos induced differentiation and migration of multipotential neural
      progenitor cells into mature oligodendrocytes localized in the corpus callosum.
      The mRNA encoding the cyclin-dependent kinase (CDK)-inhibitor p27(Kip1) was bound
      and stabilized by QKI, leading to an increased accumulation of p27(Kip1) protein
      in oligodendrocytes. Our findings demonstrate that QKI is upstream of p27(Kip1)
      during oligodendrocyte differentiation.

PMID- 15568023
TI  - Natural variation in cardiac metabolism and gene expression in Fundulus
      heteroclitus.
AB  - Individual variation in gene expression is important for evolutionary adaptation
      and susceptibility to diseases and pathologies. In this study, we address the
      functional importance of this variation by comparing cardiac metabolism to
      patterns of mRNA expression using microarrays. There is extensive variation in
      both cardiac metabolism and the expression of metabolic genes among individuals
      of the teleost fish Fundulus heteroclitus from natural outbred populations raised
      in a common environment: metabolism differed among individuals by a factor of
      more than 2, and expression levels of 94% of genes were significantly different
      (P < 0.01) between individuals in a population. This unexpectedly high variation
      in metabolic gene expression explains much of the variation in metabolism,
      suggesting that it is biologically relevant. The patterns of gene expression that
      are most important in explaining cardiac metabolism differ between groups of
      individuals. Apparently, the variation in metabolism seems to be related to
      different patterns of gene expression in the different groups of individuals. The
      magnitude of differences in gene expression in these groups is not important;
      large changes in expression have no greater predictive value than small changes.
      These data suggest that variation in physiological performance is related to the
      subtle variation in gene expression and that this relationship differs among
      individuals.

PMID- 15568024
TI  - The 'evolvability' of promiscuous protein functions.
AB  - How proteins with new functions (e.g., drug or antibiotic resistance or
      degradation of man-made chemicals) evolve in a matter of months or years is still
      unclear. This ability is dependent on the induction of new phenotypic traits by a
      small number of mutations (plasticity). But mutations often have deleterious
      effects on functions that are essential for survival. How are these seemingly
      conflicting demands met at the single-protein level? Results from directed
      laboratory evolution experiments indicate that the evolution of a new function is
      driven by mutations that have little effect on the native function but large
      effects on the promiscuous functions that serve as starting point. Thus, an
      evolving protein can initially acquire increased fitness for a new function
      without losing its original function. Gene duplication and the divergence of a
      completely new protein may then follow.

PMID- 15568025
TI  - Lethal anemia caused by interferon-beta produced in mouse embryos carrying
      undigested DNA.
AB  - The livers of DNase II-deficient mouse embryos contain many macrophages carrying
      undigested DNA, and the embryos die in utero. Here we report that erythroid
      precursor cells underwent apoptosis in the livers of DNase II-deficient embryos
      and that in the liver, interferon-beta mRNA was expressed by the resident
      macrophages. When the DNase II-deficient mice were crossed with mice deficient in
      type I interferon receptor, the resultant 'double-mutant' mice were born healthy.
      The double-mutant embryos expressed interferon-beta mRNA, but the expression of a
      subset of the interferon-responsive genes dysregulated in DNase II-deficient
      embryos was restored to normal. These results indicate that the inability to
      degrade DNA derived from erythroid precursors results in interferon-beta
      production that induces expression of a specific set of interferon-responsive
      genes associated with embryonic lethality in DNase II-deficient mice.

PMID- 15568026
TI  - B and T lymphocyte attenuator regulates T cell activation through interaction
      with herpesvirus entry mediator.
AB  - B and T lymphocyte attenuator (BTLA) provides an inhibitory signal to B and T
      cells. Previously, indirect observations suggested that B7x was a ligand for
      BTLA. Here we show that BTLA does not bind B7x; instead, we identify herpesvirus
      entry mediator (HVEM) as the unique BTLA ligand. BTLA bound the most membrane
      distal cysteine-rich domain of HVEM, distinct from regions where the ligands
      LIGHT and lymphotoxin-alpha bound HVEM. HVEM induced BTLA tyrosine
      phosphorylation and association of the tyrosine phosphatase SHP-2 and repressed
      antigen-driven T cell proliferation, providing an example of reverse signaling to
      a non-tumor necrosis factor family ligand. The conservation of the BTLA-HVEM
      interaction between mouse and human suggests that this system is an important
      pathway regulating lymphocyte activation and/or homeostasis in the immune
      response.

PMID- 15568027
TI  - Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli
      infection.
AB  - Human healthy skin is continuously exposed to bacteria, but is particularly
      resistant to the common gut bacterium Escherichia coli. We show here that
      keratinocytes secrete, as the main E. coli-killing compound, the S100 protein
      psoriasin in vitro and in vivo in a site-dependent way. In vivo treatment of
      human skin with antibodies to psoriasin inhibited its E. coli-killing properties.
      Psoriasin was induced in keratinocytes in vitro and in vivo by E. coli,
      indicating that its focal expression in skin may derive from local microbial
      induction. Zn(2+)-saturated psoriasin showed diminished antimicrobial activity,
      suggesting that Zn(2+) sequestration could be a possible antimicrobial mechanism.
      Thus, psoriasin may be key to the resistance of skin against E. coli.

PMID- 15568028
TI  - Programmable polymer thin film and non-volatile memory device.
AB  - Building on the success of organic electronic devices, such as light-emitting
      diodes and field-effect transistors, procedures for fabricating non-volatile
      organic memory devices are now being explored. Here, we demonstrate a novel
      organic memory device fabricated by solution processing. Programmable electrical
      bistability was observed in a device made from a polystyrene film containing gold
      nanoparticles and 8-hydroxyquinoline sandwiched between two metal electrodes. The
      as-prepared device, which is in a low-conductivity state, displays an abrupt
      transition to a high-conductivity state under an external bias of 2.8 V. These
      two states differ in conductivity by about four orders of magnitude. Applying a
      negative bias of 1.8 V causes the device to return to the low-conductivity state.
      The electronic transition is attributed to the electric-field-induced charge
      transfer between the gold nanoparticles and 8-hydroxyquinoline. The transition
      from the low- to the high-conductivity state takes place in nanoseconds, and is
      non-volatile, indicating that the device may be used for low-cost, high-density
      memory storage.

PMID- 15568029
TI  - Very large electro-optic responses in H-bonded heteroaromatic films grown by
      physical vapour deposition.
AB  - A crucial goal for modern telecommunications systems is development of very high
      speed components for broadband (>100 GHz), all-optical signal/information
      processing. The core component of such technologies is the electro-optic
      modulator, which encodes electrical signals onto fibre-optic transmissions. A
      significant challenge therefore is obtaining materials that have large electro
      optic responses and that can be readily fabricated into devices at low cost. We
      report here on the realization of high-response heteroaromatic organic
      chromophores that can be straightforwardly self-organized from the vapour phase
      into intrinsically acentric, high-quality, micrometre-scale films. These pi
      conjugated electro-optically active films (with second-order susceptibilities up
      to approximately 100 pm V(-1)) are thermally stable and conveniently grown by a
      simple physical vapour deposition process in a few hours. Supramolecular
      acentricity is achieved without electric field poling, enforced by biomimetic
      heterocycle-hydroxycarbonyl head-to-tail hydrogen-bonding.

PMID- 15568030
TI  - Direct imaging and mesoscale modelling of phase transitions in a nanostructured
      fluid.
AB  - The kinetics of phase transitions is essential for understanding pattern
      formation in structured fluids. These fluids play a key role in the morphogenesis
      of biological cells, and they are very common in pharmaceutical products and
      plastic materials. Until now, it has not been possible to follow phase
      transitions in structured fluids experimentally in real time and with high
      spatial resolution. Previous work has relied on static images and indirect
      experimental evidence from spatially averaging scattering experiments. Simulating
      the processes with computer models is a further challenge because of the multiple
      time and length scales involved. Our movies based on in situ scanning force
      microscopy show the time sequence of the elementary steps of a phase transition
      in a fluid film of block copolymer from the cylinder to the perforated lamella
      phase. The movies validate a versatile simulation model that gives physical
      insight into the nature of the process. Our approach provides a means of
      improving the study and understanding of pattern formation processes in
      nanostructured fluids. We expect a significant impact on nanotechnology where
      block copolymers serve as self-organized templates for the synthesis of inorganic
      nanostructured materials.

PMID- 15568031
TI  - Self-assembled polymeric solid films with temperature-induced large and
      reversible photonic-bandgap switching.
AB  - In aqueous solutions the response of polymers and biological matter to external
      conditions, such as temperature and pH, is typically based on the
      hydrophobic/hydrophilic balance and its effects on the polymer conformation. In
      the solid state, related concepts using competing interactions could allow novel
      functions. In this work we demonstrate that polymeric self-assembly,
      reversibility of hydrogen bonding, and polymer-additive phase behaviour allow
      temperature response in the solid state with large and reversible switching of an
      optical bandgap. A complex of polystyrene-block-poly(4-vinylpyridinium
      methanesulphonate) and 3-n-pentadecylphenol leads to the supramolecular comb
      shaped architecture with a particularly long lamellar period. The sample is green
      at room temperature, as an incomplete photonic bandgap due to a dielectric
      reflector is formed. On heating, hydrogen bonds are broken and 3-n
      pentadecylphenol additionally becomes soluble in polystyrene, leading to a sharp
      and reversible transition at approximately 125 degrees C to uncoloured material
      due to collapse of the long period. This encourages further developments, for
      example, for functional coatings or sensors in the solid state.

PMID- 15568032
TI  - Ultra-large-scale syntheses of monodisperse nanocrystals.
AB  - The development of nanocrystals has been intensively pursued, not only for their
      fundamental scientific interest, but also for many technological applications.
      The synthesis of monodisperse nanocrystals (size variation <5%) is of key
      importance, because the properties of these nanocrystals depend strongly on their
      dimensions. For example, the colour sharpness of semiconductor nanocrystal-based
      optical devices is strongly dependent on the uniformity of the nanocrystals, and
      monodisperse magnetic nanocrystals are critical for the next-generation multi
      terabit magnetic storage media. For these monodisperse nanocrystals to be used,
      an economical mass-production method needs to be developed. Unfortunately,
      however, in most syntheses reported so far, only sub-gram quantities of
      monodisperse nanocrystals were produced. Uniform-sized nanocrystals of CdSe (refs
      10,11) and Au (refs 12,13) have been produced using colloidal chemical synthetic
      procedures. In addition, monodisperse magnetic nanocrystals such as Fe (refs
      14,15), Co (refs 16-18), gamma-Fe(2)O(3) (refs 19,20), and Fe(3)O(4) (refs 21,22)
      have been synthesized by using various synthetic methods. Here, we report on the
      ultra-large-scale synthesis of monodisperse nanocrystals using inexpensive and
      non-toxic metal salts as reactants. We were able to synthesize as much as 40 g of
      monodisperse nanocrystals in a single reaction, without a size-sorting process.
      Moreover, the particle size could be controlled simply by varying the
      experimental conditions. The current synthetic procedure is very general and
      nanocrystals of many transition metal oxides were successfully synthesized using
      a very similar procedure.

PMID- 15568033
TI  - Therapeutic dendritic-cell vaccine for chronic HIV-1 infection.
AB  - We present the results of a preliminary investigation of the efficacy of a
      therapeutic dendritic cell (DC)-based vaccine for HIV-1. We immunized 18
      chronically HIV-1-infected and currently untreated individuals showing stable
      viral loads for at least 6 months with autologous monocyte-derived DCs loaded
      with autologous aldrithiol-2-inactivated HIV-1. Plasma viral load levels were
      decreased by 80% (median) over the first 112 d following immunization. Prolonged
      suppression of viral load of more than 90% was seen in 8 individuals for at least
      1 year. The suppression of viral load was positively correlated with HIV-1
      specific interleukin-2 or interferon-gamma-expressing CD4(+) T cells and with HIV
      1 gag-specific perforin-expressing CD8(+) effector cells, suggesting that a
      robust virus-specific CD4(+) T-helper type 1 (T(H)1) response is required for
      inducing and maintaining virus-specific CD8(+) effectors to contain HIV-1 in
      vivo. The results suggest that inactivated whole virus-pulsed DC vaccines could
      be a promising strategy for treating people with chronic HIV-1 infection.

PMID- 15568034
TI  - Impact of CD34 subsets on engraftment kinetics in allogeneic peripheral blood
      stem cell transplantation.
AB  - Our objective was to evaluate, probably for the first time, the impact of CD34
      subsets on engraftment kinetics in allogeneic PBSC transplantation (PBSCT). PBSC
      graft components were analyzed in 62 cases for the absolute count/kg of total
      CD34+ and the following subsets: DR- and +, CD71+/-, CD38+/-, CD33+/- and CD61+/
      . Time to ANC >0.5 and >1 x 10(9)/l and platelets >20 and >50 x 10(9)/l was
      reported. The median value for each parameter was used to discriminate rapid from
      slow engraftment. Four parameters showed significant predictive power of early
      neutrophil engraftment, namely CD34+ /DR- (P = 0.002), CD34+/38- (P = 0.02),
      CD34+/CD61- (P = 0.04) and total CD34+ cell dose (P = 0.04). Four parameters
      showed significant predictive power of early platelet engraftment, namely
      CD34+/CD61+ (P = 0.02), CD34+ /CD38- and total CD34+ cell dose (P = 0.04) and
      CD34+ /CD71- (P = 0.05). Comparing patients who received > to those who received
      < the threshold dose(s), only CD34+ /CD38- lost its significance for neutrophil
      engraftment; and only CD34+ /CD61+ retained its significance for platelet
      engraftment (P = 0.03); furthermore, the former group required significantly
      fewer platelet transfusions (P = 0.018). We concluded that in allogeneic PBSCT,
      the best predictor of early neutrophil engraftment is the absolute CD34+ /DR- and
      for early platelet engraftment is the absolute CD34+ /CD61+ cell dose.

PMID- 15568035
TI  - Autoimmune thrombocytopenia with clonal expansion of CD8-positive T cells after
      autologous peripheral blood stem cell transplantation for diffuse large B-cell
      lymphoma.

PMID- 15568036
TI  - Rituximab is effective in the management of refractory autoimmune cytopenias
      occurring after allogeneic stem cell transplantation.
AB  - Autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and
      autoimmune neutropenia (AIN) are well-recognised complications of allogeneic stem
      cell transplantation (SCT), but have previously only been reported in the context
      of myeloablative conditioning regimens. Management of AIHA, ITP or AIN occurring
      after allogeneic SCT is unsatisfactory since they frequently prove refractory to
      conventional therapies including splenectomy. As a consequence, autoimmune
      cytopenias occurring after allogeneic SCT are associated with substantial
      morbidity and mortality. We report four patients who developed AIHA or ITP after
      allogeneic transplantation -- three of which occurred after a reduced-intensity
      conditioning (RIC) regimen. All patients demonstrated a complete response to
      Rituximab, having failed to respond to conventional treatment including high-dose
      prednisolone and intravenous immunoglobulin (IVIg). We conclude that Rituximab
      can be a valuable agent in the management of autoimmune cytopenias occurring
      after allogeneic SCT and that autoimmune cytopenias may be a hitherto
      unrecognised complication of RIC regimens.

PMID- 15568037
TI  - Accidental busulfan overdose during conditioning for stem cell transplantation.
AB  - High dose busulfan is widely used in preparative regimens for bone marrow
      transplantation. We describe three cases of accidental busulfan overdosing. Two
      adults received a single dose of 8 and 18 mg/kg busulfan, respectively. Doses of
      9 x 4 mg/kg were ingested by a 14-year-old girl, who experienced seizures. In all
      cases, no severe liver toxicity including veno-occlusive disease was observed.
      Plasma samples were obtained from two patients. Busulfan plasma concentrations
      were far above published values after high-dose busulfan treatment. Busulfan was
      eliminated by a first-order process. All patients survived these high doses of
      busulfan and successful transplantation was possible. Two patients died from
      refractory GvHD on days 91 and 80 after transplantation. One patient is alive in
      remission after an observation time of 18 months. These cases show that busulfan
      overdosing may occur and pharmacokinetic evaluation is warranted to estimate risk
      of early and late toxicity.

PMID- 15568038
TI  - The role of shear stress in the pathogenesis of atherosclerosis.
AB  - Although the pathobiology of atherosclerosis is a complex multifactorial process,
      blood flow-induced shear stress has emerged as an essential feature of
      atherogenesis. This fluid drag force acting on the vessel wall is
      mechanotransduced into a biochemical signal that results in changes in vascular
      behavior. Maintenance of a physiologic, laminar shear stress is known to be
      crucial for normal vascular functioning, which includes the regulation of
      vascular caliber as well as inhibition of proliferation, thrombosis and
      inflammation of the vessel wall. Thus, shear stress is atheroprotective. It is
      also recognized that disturbed or oscillatory flows near arterial bifurcations,
      branch ostia and curvatures are associated with atheroma formation. Additionally,
      vascular endothelium has been shown to have different behavioral responses to
      altered flow patterns both at the molecular and cellular levels and these
      reactions are proposed to promote atherosclerosis in synergy with other well
      defined systemic risk factors. Nonlaminar flow promotes changes to endothelial
      gene expression, cytoskeletal arrangement, wound repair, leukocyte adhesion as
      well as to the vasoreactive, oxidative and inflammatory states of the artery
      wall. Disturbed shear stress also influences the site selectivity of
      atherosclerotic plaque formation as well as its associated vessel wall
      remodeling, which can affect plaque vulnerability, stent restenosis and smooth
      muscle cell intimal hyperplasia in venous bypass grafts. Thus, shear stress is
      critically important in regulating the atheroprotective, normal physiology as
      well as the pathobiology and dysfunction of the vessel wall through complex
      molecular mechanisms that promote atherogenesis.

PMID- 15568039
TI  - The human tumor suppressor CEACAM1 modulates apoptosis and is implicated in early
      colorectal tumorigenesis.
AB  - Defects in the adenomatous polyposis coli (APC) tumor suppressor pathway are
      sufficient for neoplastic transformation as the initiating step in colorectal
      carcinogenesis. In contrast, hyperplastic tumors possess normal APC function, and
      it is unclear whether they represent significant precursor lesion in cancer
      development. CEACAM1 is a tumor suppressor whose expression is known to be lost
      in the great majority of early adenomas and carcinomas. We found that loss of
      CEACAM1 expression is more common in neoplastic tumors than APC mutations. While
      APC function was normal in hyperplastic aberrant cypt foci and hyperplastic
      polyps, loss of CEACAM1 was observed as frequently as in the neoplasias.
      Moreover, the presence or absence of CEACAM1 expression in the hyperplastic
      tumors correlates with normal or reduced apoptosis, respectively. In vitro,
      CEACAM1 acts as a regulator of apoptosis in CEACAM1-transfected Jurkat cells.
      Finally, in human HT29 colon cancer cells, apoptosis can be specifically restored
      by induction of CEACAM1 expression. These data suggest an oncodevelopmental link
      between neoplasia and hyperplasia and demonstrate that CEACAM1 acts as a
      regulator of apoptosis in the colonic epithelium. Thus, failure of the maturing
      colon cell to express CEACAM1 is likely to contribute to the development of
      hyperplastic lesions, which may eventually pave the way to neoplastic
      transformation and colon cancer development.

PMID- 15568040
TI  - Wetting and hydration of insoluble soot particles in the upper troposphere.
AB  - Wettability and hydration are determined for aircraft combustor and laboratory
      made soots which are used as surrogates for the insoluble part of aircraft
      generated black carbon particles in the upper troposphere (UT). The measured
      water/ice contact angles on the soot surfaces are in the range 60-80 degrees.
      Factors influencing the soot wetting show a tremendous dependence on the surface
      chemical composition and microstructure. Wetting characteristics of soots are
      directly related to its hydrophilicity. The inverse Kelvin effect is considered
      as a mechanism of ice nucleation which is facilitated by the soot agglomerated
      structure with interparticle cavities in which condensation takes place on the
      insoluble surface with a high water contact angle. Estimations of the critical
      supersaturations needed for the ice condensation growth of particles are provided
      to determine which of the wetting characteristics are required for cirrus cloud
      formation in ice saturated regions of the UT.

PMID- 15568041
TI  - High frequency monitoring reveals phytoplankton dynamics.
AB  - Phytoplankton is an important water quality indicator because of its high species
      differentiation, growth rates and responsiveness to environmental actuators. The
      new European Water Framework Directive calls for assessment of the duration,
      intensity and succession of phytoplankton blooms to determine the ecological
      status of various types of waters. For common phytoplankton growth rates basic
      signal processing theory yields a minimum monitoring frequency of once per day,
      which is much more than applied in standard practice. To assess the nature of
      this discrepancy we followed the behaviour of about 40 groups of
      organisms/particles found in the Oude Rijn river by a two-week daily cytometric
      analysis. Particle counts of the 20 most abundant groups are shown. Their
      variation rate and magnitude confirm that daily sampling is needed to follow such
      ecosystems in detail. It is shown that limiting the monitoring to the "coarse
      line" does not allow a correspondingly decreased sampling frequency. Automated
      systems may fill the gaps between the microscopical examinations by gathering
      highly frequent information. The information depth of bulk measurements is poor
      however, and not used as such. The data shown here demonstrate that modern
      scanning flow cytometry (SFC) offers an information depth close to the taxonomic
      level. In the past decade, acquisition and operation costs of these systems have
      come down considerably, whereas operation is hands free, even in situ and
      submerged, and data analysis has become more efficient. SFC is used most
      efficiently complementary to microscopical analyses for mutual validation. In
      these cases it presents a realistic solution to generate the essential high
      frequency observations required to assess ecosystem variability.

PMID- 15568042
TI  - The effect of temperature and NaCl concentration on the kinetic method of
      toxicity determination using Vibrio fischeri.
AB  - In this paper the effect of temperature and NaCl concentration on the kinetic
      method of toxicity determination using Vibrio fischeri was studied for 50 ppm
      Zn(2+). This work shows that both NaCl concentration and temperature affect the
      kinetics of toxicity as well as the luminescence of the bacteria, and hence these
      are important factors that need to be considered in the development of a
      miniaturised portable instrument. Furthermore, this work shows that the
      conditions for which the kinetic test was most sensitive, i.e. exhibited the
      greatest response, were 23 degrees C and 2% NaCl. However, at these conditions
      small variations in temperature and NaCl concentration could lead to great errors
      in the results. Thus 12.5 degrees C and 2% NaCl are preferred as at these
      conditions the obtained results are more robust. Although at the latter
      conditions the toxicity rate constant was found to be 5.5 times less than that
      for 23 degrees C, the value is comparable to that obtained for 15 degrees C. From
      the data available it was also found that the temperature dependence of the
      toxicity rate fits the Arrhenius equation, in a behaviour similar to that of
      simpler chemical reactions.

PMID- 15568043
TI  - Can NO(2) be used to indicate ambient and personal levels of benzene and 1,3
      butadiene in air?
AB  - The aim of this study was to investigate the relation between two toxic volatile
      organic compounds, 1,3-butadiene and benzene, and a commonly used indicator of
      vehicle exhaust fumes, NO(2). This was to see if NO(2) can be used to indicate
      personal exposure to carcinogenic substances or at least estimate ambient levels
      measured at a stationary point. During the winter of 2001, 40 randomly selected
      persons living in the City of Umea (in the north of Sweden) were recruited to the
      study. Personal measurements of 1,3-butadiene, benzene and NO(2) were performed
      for one week, and were repeated for 20 of the 40 participants. Additional
      information was gathered using a diary kept by each participant. During the same
      time period weekly stationary measurements were performed at one urban background
      station and one street station in the city centre. The results from the personal
      measurements showed a negligible association of NO(2) with 1,3-butadiene (r=
      0.06) as well as with benzene (r= 0.10), while the correlation coefficient
      between 1,3-butadiene and benzene was high and significant (r= 0.67). In contrast
      to the personal measurements, the stationary measurements showed strong relations
      between 1,3-butadiene, benzene and NO(2) both within and in-between the street
      and urban background station. This study supports NO(2) as a potential indicator
      for 1,3-butadiene and benzene levels in streets or urban background air, while
      the weak relations found for the personal measurements do not support the use of
      NO(2) as an indicator for personal 1,3-butadiene and benzene exposure.

PMID- 15568044
TI  - A multiresidue method for the analysis of phenols and nitrophenols in the
      atmosphere.
AB  - A method using GC-MS and derivatization with N-(t-butyldimethylsilyl)-N
      methyltrifluoroacetamide (MTBSTFA) was developed for the analysis of 20 phenolic
      compounds in atmospheric samples (gas and particles). Air sampling was carried
      out using a Hi-Vol sampler with glass fibre filter and XAD-2 resin at a flow rate
      of 60 m(3) h(-1). The particle and gas phases were collected separately over a
      period of 4 h. Samples were Soxhlet extracted, evaporated to dryness under
      nitrogen and refilled with acetonitrile. 100 microl of these extracts were
      derivatized with 100 microl of MTBSTFA at 80 degrees C for 1 h under strong
      stirring. Phenolic compounds were injected into a GC-MS in splitless mode and
      quantified as their TBDMS derivatives in the SIM mode. Mass spectral analysis of
      the derivatives of the 20 compounds studied indicates that the spectra are highly
      specific showing an ion at [M - 57]+ which is useful for structure confirmation
      or analysis at low levels using selected ion monitoring. Quantification limits
      varied between 5 microg l(-1) and 10 microg l(-1) which correspond to 20 pg m(-3)
      and 40 pg m(-3) for 250 m(3) of air sampled. This method was successfully applied
      to atmospheric samples.

PMID- 15568045
TI  - Biological responses of workplace particles and their association with adverse
      health effects on miners.
AB  - Epidemiological research has demonstrated the relationship between exposure to
      quartz dust and an elevated risk of pneumoconiosis and possible elevated risk of
      cancer. The current study was designed to evaluate the biological responses of
      workplace particles containing crystalline silica using an in vitro cell test.
      Respirable particle samples were sampled from four tin mines, where the
      standardized mortality ratio (SMR) for pneumoconiosis was 51.6 and SMR for lung
      cancer was 2.2 in dust-exposed miners. Alveolar macrophages (AM) are considered
      as the target cells for primary dust effects. The samples were then measured at
      15, 30, 60 and 120 microg particle per 10(6) AM for cytoxicity with the release
      of glucuronidase, lactate dehydrogenase, for reactive oxygen damage with H(2)O(2)
      release, and for ability to induce fibrosis using the secretion of tumor necrosis
      factor-alpha (TNF-alpha). Pure quartz (DQ12) and corundum were used as controls.
      The results showed the samples from tin mines caused a higher cytoxicity when
      compared to corundum, yet lower when compared to quartz. However, reactive oxygen
      species release (148-177 nmol/3 x 10(5) AM in high concentration of 120
      microg/10(6) AM) induced by the samples were significantly higher than that
      induced by quartz (57 nmol/3 x 10(5) AM) and corundum (62 nmol/3 x 10(5) AM).
      Furthermore, particle samples induced higher TNF-alpha secretion than corundum,
      the samples from Limu tin mine induced much higher TNF-alpha levels than that
      induced by DQ12 quartz. The results from the in vitro tests help elucidate the
      degree of hazard of dust particles in tin mines. The in vitro reaction patterns
      of AM also constitute a powerful tool to monitor biological and pathogenic
      responses of humans following dust particle exposure.

PMID- 15568046
TI  - Evaluation of the SKC DPM cassette for monitoring diesel particulate matter in
      coal mines.
AB  - In a previous study, the efficacy of commercial and prototype impactors for
      sampling diesel particulate matter (DPM) in coal mines was investigated.
      Laboratory and field samples were collected on quartz-fiber filters and analyzed
      for organic and elemental carbon. Coal dust contributed a minimal amount of
      elemental carbon when commercial cascade impactors and prototype impactors,
      designed by the University of Minnesota (UMN) and the US Bureau of Mines (BOM),
      were used to collect submicrometer dust fractions. Other impactors were not as
      effective at excluding coal dust. The impactors evaluated in that study were
      either not commercially available or were multi-stage, expensive, and difficult
      to use for personal measurements. A commercial version of the BOM impactor,
      called the DPM Cassette, was recently introduced by SKC. Tests were conducted to
      evaluate the performance of the DPM Cassette for measuring diesel-source
      elemental carbon in the presence of coal dust. Bituminous coals from three mines
      in two different coal provinces were examined. The dust particle diameters were
      small and the coal dust contained a high percentage of carbon, thereby giving a
      worst-case condition for non-anthracite coal mines. Results for the DPM Cassette
      were essentially identical to those obtained by the BOM impactors in a previous
      study. At a respirable coal dust concentration of 5.46 mg m(-3), which is 3.8
      times the regulatory limit, the DPM Cassette collected only 34 microg m(-3) of
      coal-source elemental carbon.

PMID- 15568047
TI  - Development and validation of methods for environmental monitoring of
      cyclophosphamide in workplaces.
AB  - Methods to monitor contamination of workplaces with antineoplastic drugs have
      been developed and validated. Cyclophosphamide (CP) was used as a model compound
      as it is one of the most commonly used antineoplastic drugs. A wipe sampling
      method to detect contamination with CP at surfaces was developed. A personal air
      sampling method to sample gas and vapour on solid sorbent tubes and particles
      with filters was also developed. Wipe and filter samples were extracted and
      sorbent samples were eluted, all with ethyl acetate. The samples were analysed
      with liquid chromatography tandem mass spectrometry. (2)H(6)-labelled
      cyclophosphamide was used as an internal standard. The between-day precision was
      2-5% for wipe samples, 4-6% for sorbent samples and 3-8% for filter samples. The
      limit of detection was 0.02 ng CP per sample for the wipe and filter methods and
      0.03 ng CP per sample for the solid sorbent method. Wipe sampling on surfaces
      made of different materials resulted in mean recoveries between 78-106%. The
      desorption recovery was between 97-102% for the wipe samples, 97% for the sorbent
      samples and 101% for the filter samples. Samples were stable for up to 2 months
      at 5 degrees C and -20 degrees C and for about 2 d at room temperature. The
      developed methods were applied to the measurement of contamination with CP in a
      hospital pharmacy. Trace amounts of CP, 1.3 and 1.4 ng, were detected on surfaces
      in the pharmacy.

PMID- 15568048
TI  - Multi-component assessment of worker exposures in a copper refinery. Part 1.
      Environmental monitoring.
AB  - The exposure characterisation described in this paper for 135 copper refinery
      workers (45 females, 90 males) focuses on the concentrations of copper, nickel
      and other trace elements in the inhalable aerosol fractions, as well as in the
      water-soluble and water-insoluble subfractions. Some information is also provided
      on the thoracic and respirable aerosol fractions. Further, results are presented
      for volatile hydrides of arsenic and selenium released in the copper purification
      steps of the electrorefining process. For the pyrometallurgical operations, a
      comparison of the geometric means for the inhalable aerosol fraction indicated
      that water-soluble copper levels were on average 19-fold higher compared to
      nickel (p < 0.001) and a significant association was evident between them (r =
      0.87, p < 0.001); for the insoluble subfraction, the copper : nickel ratio was
      12.5 (p < 0.001) and the inter-element correlation had r = 0.98 and p < 0.001.
      Although for the electrorefinery workers the relative inhalable concentrations of
      copper and nickel were not significantly different (p > 0.05), the corresponding
      inter-element associations were: slope of 7.7, r= 0.54, p < or =0.001 for the
      water-soluble subfraction and slope of 1.3, r = 0.71 and p < or =0.001 for the
      water-insoluble subfraction. On average, a good proportion of the inhalable
      copper and nickel were found in the thoracic (40%) and respirable (20%) aerosol
      fractions. Cobalt air concentrations were generally low with geometric means and
      95% confidence intervals of 3.1 (2.4-4.2)microg m(-3) (pyrometallurgical workers)
      and 0.3 (0.4-0.5) microg m(-3)(electrorefinery workers). Similarly, the maximum
      concentrations of cadmium and lead were low, respectively 4 and 25 microg m(-3).
      Of the hydrides, tellurium and antimony could not be detected, but for the
      arsenic (arsine) and selenium hydrides measurable exposure occurred for almost
      all electrorefinery workers, although the levels were generally low at 0.2 microg
      m(-3).

PMID- 15568049
TI  - New chemistry on old CDs.
AB  - Old compact discs (CDs) have been found to be useful for modern chemical
      research. Their metal reflective film is suitable for the preparation of high
      quality self-assembled monolayers (SAMs) and for electrochemical analysis; pre
      grooved polycarbonate base is ideal for the "customized" fabrication of material
      micro/nanostructures; and the immobilization of biomolecules on CDs, in
      conjunction with a conventional CD drive, promises to be an inexpensive tool for
      point-of-care biomedical diagnosis and gene analysis.

PMID- 15568050
TI  - Dendrimers and gold nanoparticles as exo-receptors sensing biologically important
      anions.
AB  - Dendrimers, alkylthiol-gold nanoparticles and gold-nanoparticle-cored dendrimers
      containing tethers terminated by a redox group (typically an iron sandwich)
      attached to a hydrogen-bonding group (amido, amino, silyl) are selective and
      efficient exo-receptors for the recognition, sensing and titration of oxo-anions,
      including ATP(2-), or halogens, mostly using cyclic voltammetry. Various positive
      dendritic effects were disclosed (in contrast to catalysis), and large gold
      nanoparticle-cored redox dendrimers of this type that contain several hundred
      equivalent ferrocenyl groups readily adsorb on Pt electrodes, providing useful
      regenerable electrochemical sensors.

PMID- 15568051
TI  - Principles of sequence-recognition in aromatic polyimides.
AB  - Pyrene-based molecular tweezers show sequence-specific binding to aromatic
      polyimides through sterically-controlled donor-acceptor pi-stacking and hydrogen
      bonding; (1)H NMR spectra of tweezer-complexes with polyimides having different
      sequence-restrictions show conclusively that the detection of long range sequence
      information results from multiple tweezer-binding at adjacent imide residues.

PMID- 15568052
TI  - Metalloglycomics: a new perspective upon competitive metal-carbohydrate binding
      using EPR spectroscopy.
AB  - Ternary complexes formed between calcium, the oxochromium(v) ion and N
      acetylneuraminic (sialic) acid (naH(6)) of the form, Ca(ii)-oxoCr(v)-naH(6), have
      electronic structures and equilibrium distributions distinct from the binary
      oxoCr(v)-naH(6) analogues, as illustrated by electron paramagnetic resonance
      (EPR) spectroscopy.

PMID- 15568053
TI  - Novel cerium(IV) heteropolyoxotungstate containing two types of lacunary Keggin
      anions.
AB  - A novel V-shaped polyoxotungstate is formed when Ce(IV) metal centres bridge
      monolacunary [PW(11)O(39)](7-) anions to an unusual 1,4-bilacunary
      [PW(10)O(38)](11-) anion which appears with an unprecedented bridging structural
      motif.

PMID- 15568054
TI  - Synthesis and X-ray crystal structure of an anionic heteronuclear
      metallamacrocyclic triangle.
AB  - trans-[Pt(C[triple bond]C(Ar)C[triple bond]CH)2(PMe3)2](Ar = C(6)Me(4)-3,4,5,6)
      (1) reacts with PPN[Au(acac)(2)](Hacac = acetylacetone; 1 : 1.16 molar ratio; PPN
      = (Ph3P)2N) to give PPN[(Au[Pt(PMe3)2]2)(mu-Ar(C[triple bond]C)2)3] (2) the
      crystal structure of which showed the anions as quasi equilateral triangles
      stacked parallel to each other through C-HAu interactions, resulting in channels
      of rhombic cross-section.

PMID- 15568055
TI  - Novel 36-membered dodecanuclear manganese metalladiazamacrocycle.
AB  - A novel dodecanuclear manganese metalladiazamacrocycle was synthesized employing
      a new pentadentate ligand N-2-pentenoylsalicylhydrazide (H(3)tpeshz) by
      supramolecular self-assembly. The backbone of this metal-organic assembly is a
      repeating unit of an M-N-N-M linkage that extends to complete a 36-membered
      cyclic structure involving 12 manganese(III) centers. Successive manganese
      centers are in a chemically different ...ABABAB...-type environment while the
      chirality varies as ...LambdaLambdaDeltaDeltaLambdaLambda... . The unique
      arrangement of manganese centers results in a highly puckered
      metalladiazamacrocycle with an S(6)-point group symmetry.

PMID- 15568056
TI  - Helical coordination polymers and cyclic dimers formed from heteroleptic
      thioether-dipyrrinato copper(II) complexes.
AB  - Heteroleptic copper complexes containing an acetylacetonato ligand and a
      thioether derivatized dipyrrinato ligand are shown to form oligomers and polymers
      in the solid state.

PMID- 15568057
TI  - Self-assembly of a pi-electronic amphiphile consisting of a zinc porphyrin
      fullerene dyad: formation of micro-vesicles with a high stability.
AB  - An amphiphilic zinc porphyrin-fullerene dyad appended with triethyleneglycol
      chains in aqueous media forms uniformly-sized multilamellar vesicles with a mean
      diameter of 100 nm that are thermally stable and robust against membrane lysis
      with surfactants.

PMID- 15568058
TI  - Al(OPr i)3-catalysed halogen exchange processes of relevance to atom transfer
      radical polymerization: the effect depends on the metal electronic structure.
AB  - Whether or not tri(isopropoxo)aluminium catalyses halogen exchange for an ATRP
      catalyst depends on the number of valence electrons.

PMID- 15568059
TI  - Synthesis and characterization of a benzene-centered, phthalocyanine hexamer.
AB  - The first benzene-centered, phthalocyanine hexamer has been synthesized by a
      dicobaltoctacarbonyl-catalyzed trimerization reaction of an ethynyl-bridged
      bisphthalocyanine and characterized by different spectrometric and spectroscopic
      techniques.

PMID- 15568060
TI  - Formation of dimers of inclusion cryptand/paraquat complexes driven by dipole
      dipole and face-to-face pi-stacking interactions.
AB  - Dimers of inclusion complexes were formed from a new cryptand and viologens
      (paraquats) driven by dipole-dipole and face-to-face pi-stacking interactions as
      shown by mass spectrometric characterization and X-ray analysis.

PMID- 15568061
TI  - Selective formation of siloxane-based hybrid cages with methylene groups in the
      frameworks.
AB  - A new class of cage-like oligomers were selectively formed by hydrolysis and
      polycondensation of a methylene-bridged bistrialkoxysilane precursor in the
      presence of tetramethylammonium hydroxide, which led to the creation of novel
      silica-based hybrid materials.

PMID- 15568062
TI  - Ensemble hybridisation--a new method for exploring sequence dependent
      fluorescence of dye-nucleic acid conjugates.
AB  - The fluorescence of thiazole orange as artificial base in PNA was investigated in
      a nearest neighbour analysis; library-to-library hybridisation allowed the
      identification of probe sequences suitable for homogeneous DNA detection.

PMID- 15568063
TI  - Selective growth of a less stable polymorph of 2-iodo-4-nitroaniline on a self
      assembled monolayer template.
AB  - Orthorhombic and triclinic crystals of 2-iodo-4-nitroaniline (INA) grow
      concomitantly from supersaturated ethanol solutions, but the less stable
      orthorhombic phase can be selectively grown on 3'-X-4-mercaptobiphenyl (X =
      NO(2), I) self-assembled monolayer templates.

PMID- 15568064
TI  - A neutral self-assembled coordination cage organized for inclusion of aromatic
      guests.
AB  - Jahn-Teller distorted Cu2+ centers, axially ligated by RSO(3)(-) groups, act as
      spacers to form a cage molecule with ligands organized at a distance well-suited
      for inclusion of aromatics.

PMID- 15568065
TI  - Regioselective Hula-twist photoisomerization of cinnamate esters in organic
      glass.
AB  - Irradiation of ethyl cis-o-fluorocinnamate and related compounds in organic glass
      led to two HT-isomerization processes that exhibit a strong preference at C-beta
      than at C-alpha as shown by low temperature UV absorption spectroscopy and
      supported by ab initio calculations.

PMID- 15568066
TI  - Doubly N-fused meso-aryl substituted hexaphyrins(1.1.1.1.1.1).
AB  - Doubly N-fused hexaphyrins were synthesized from meso-aryl substituted
      hexaphyrins and X-ray crystallography revealed that syn- or anti-double N-fusion
      occurred, depending on the positions of meso-substituents.

PMID- 15568067
TI  - Coordination polymers with macrocyclic cages and pockets within their backbones.
AB  - The reaction between the flexible ligand (1,4-bis(pyridine-2-yl
      methanethio)benzene) and Ag+ produces two novel coordination polymers with
      macrocyclic cages or pockets contained within their backbones, depending upon the
      ratio of starting materials.

PMID- 15568068
TI  - Crystallography and magnetism of radicals with hindered hydroxyl groups: 2-(3,5
      di-tert-butyl-4-hydroxyphenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3
      oxide-1-oxyl and 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4,4,5,5-tetramethyl-4,5
      dihydro-1H-imidazole-1-oxyl.
AB  - Radicals form networks of OH... ON and OH...Me(nitroxide) interactions. In 2, a
      frustrated network forms with insufficient N-O units to form extended chain
      interactions. The magnetism of 1 fits a 1-D Heisenberg model with J/k=-25 J mol(
      1), while 2 shows more complex exchange behaviour consistent with its disordered
      crystal lattice.

PMID- 15568069
TI  - Influence of EDA-pi interactions in drug encapsulation using nanospheres.
AB  - We have evaluated the influence of aromatic and hydrophobic interactions on the
      strength and selectivity of encapsulation using polymeric nanospheres.

PMID- 15568070
TI  - Enzymatic preparation of biotinylated naturally-occurring sialylglycan and its
      molecular recognition on a quartz-crystal microbalance.
AB  - A biotinylated sialylglycan was prepared enzymatically by endo-M, and binding
      behavior of an SSA lectin was studied on a different coverage of a sialylglycan
      immobilized 27 MHz quartz-crystal microbalance (QCM).

PMID- 15568071
TI  - Selenocatalytic alpha-halogenation.
AB  - Through a 2e- oxidation-reduction cycle, phenylselenides catalytically activate N
      chlorosuccinimide toward electrophilic reactions with ketones, resulting in alpha
      haloketones.

PMID- 15568072
TI  - Donor-rich and acceptor-rich pyridine-phosphadiazonium adducts: diversifying the
      Lewis acceptor chemistry of phosphorus(III).
AB  - [Mes*NP(DMAP)2][OTf] represents the first ligand-rich coordination complex of a
      phosphorus(III) Lewis acceptor, and a three coordinate hypervalent electron-rich
      (lone pair bearing) center; further diversification is demonstrated by,
      [(Mes*NP)2(4,4'-BIPY)][OTf]2, representing an acceptor-rich dication.

PMID- 15568073
TI  - Chemical routes to GeS2 and GeSe2 nanowires.
AB  - Nanowires of GeS(2) and GeSe(2) have been obtained by novel chemical routes
      involving the decomposition of organo-ammonium precursors containing super
      tetrahedral Ge(4)S(10) and the dimeric Ge(2)Se(6) units.

PMID- 15568074
TI  - Attachment of glycosaminoglycan oligosaccharides to thiol-derivatised gold
      surfaces.
AB  - Glycosaminoglycan oligosaccharides have been attached to thiol-derivatised gold
      surfaces, via the formation of mercury-sugar adducts at the non-reducing end,
      representing a new method of generating versatile glycoconjugates incorporating
      this class of biologically and medically important carbohydrate.

PMID- 15568075
TI  - Synthesis of C-arylglycosides via Ru(II)-catalyzed [2 + 2 + 2] cycloaddition.
AB  - In the presence of catalytic amounts of Cp*RuCl(cod), the cycloaddition of 1,6
      diynes with various C-alkynylglycosides proceeded at ambient temperature to
      afford C-arylglycosides in 46-93% yields.

PMID- 15568076
TI  - Supramolecular control of complexation-induced fluorescence change of water
      soluble, beta-cyclodextrin-modified CdS quantum dots.
AB  - The fluorescence of beta-cyclodextrin-modified CdS quantum dots can be reversibly
      tuned by introducing different substrates in aqueous media.

PMID- 15568077
TI  - Flexible enzymatic and chemo-enzymatic approaches to a broad range of uridine
      diphospho-sugars.
AB  - Enzymatic and chemo-enzymatic approaches provide straightforward access to
      uridine diphospho sugars irrespective of the relative and absolute configuration
      of the sugar, its ring size and substitution pattern.

PMID- 15568078
TI  - Synthesis and characterization of multiferroic BiFeO3 nanotubes.
AB  - Multiferroic bismuth ferrite (BiFeO(3)) nanotubes have been synthesized using a
      modified template methodology and characterized by a number of techniques,
      including XRD, SEM, TEM, HRTEM as well as EDX and SAED.

PMID- 15568079
TI  - CeZSM-5--a designer's catalyst for selective synthesis of octahydroacridine.
AB  - High activity of cyclohexanone, formaldehyde and ammonia to form 1,2,3,4,5,6,7,8
      octahydroacridine (OHA) is observed over different classes of zeolites and
      molecular modeling studies confirm the suitability of HZSM-5 catalyst for
      selective synthesis of OHA.

PMID- 15568080
TI  - Ruthenium- and gold-catalysed sequential reactions: a straightforward synthesis
      of substituted oxazoles from propargylic alcohols and amides.
AB  - A convenient and straightforward one-pot reaction of propargylic alcohols bearing
      a terminal alkyne moiety with amides by the sequential action of ruthenium and
      gold catalysts gives the corresponding substituted oxazoles in good yields with a
      complete regioselectivity.

PMID- 15568081
TI  - Aqueous hydrogenation of carbon dioxide catalysed by water-soluble ruthenium aqua
      complexes under acidic conditions.
AB  - Hydrogenation of carbon dioxide (P(H2/CO2)= 5.5/2.5 MPa) into formic acid (HCOOH)
      under acidic conditions (pH 2.5-5.0) in water has been achieved by using water
      soluble ruthenium aqua catalysts [(eta6-C6Me6)RuII(L)(OH2)]SO4 (L = 2,2'
      bipyridine or 4,4'-dimethoxy-2,2' bipyridine).

PMID- 15568082
TI  - [Ru(eta3-2-C3H4Me)(CO)(dppf)][SbF6]: a mononuclear 16e - ruthenium(II) catalyst
      for propargylic substitution and isomerization of HC[triple bond]CCPh2(OH).
AB  - The 16e(-) derivative [Ru(eta3-2-C3H4Me)(CO)(dppf)][SbF6] catalyzes: (i) the
      propargylic substitution reaction of 1,1-diphenyl-2-propyn-1-ol with alcohols to
      produce propargylic ethers, and (ii) the formal isomerization of 1,1-diphenyl-2
      propyn-1-ol into 3,3-diphenyl-2-propenal.

PMID- 15568083
TI  - A "Nitrate Route" for the low temperature "Fast SCR" reaction over a V2O5
      WO3/TiO2 commercial catalyst.
AB  - A novel mechanism is proposed for the Fast SCR reaction of NH(3), NO and NO(2) at
      low temperature involving the formation of ammonium nitrate as intermediate and
      its subsequent reaction with NO as the rate determining step.

PMID- 15568084
TI  - Manipulation of the stereochemical outcome and product distribution in the Henry
      reaction using CO2 pressure.
AB  - The rate and stereocontrol of the Henry reaction in the presence of CO(2) can be
      controlled simply by manipulation of CO(2) pressure, and can be understood by
      consideration of the kinetic and thermodynamic aspects of the reaction.

PMID- 15568085
TI  - The electrochemically tuneable recognition properties of an electropolymerised
      flavin derivative.
AB  - The electrochemically tuneable recognition properties between an
      electropolymerised flavin derivative and 2,6-diethylamidopyridine are reported.

PMID- 15568086
TI  - A facile chemical route to semiconductor metal sulfide nanocrystal superlattices.
AB  - We report a facile chemical route for the synthesis of monodisperse nanocrystals
      of various metal sulfides (PbS, Cu(2)S, and Ag(2)S) and their assemblies into
      nanocrystal superlattices (NCSs); the sulfides NCSs were precipitated by adding
      ethanol to nanocrystal colloids, which were obtained directly by a reaction
      between metal thiolate and thioacetamide in a pure dodecanethiol solvent.

PMID- 15568087
TI  - Magnetic nanochains of metal formed by assembly of small nanoparticles.
AB  - Ni nanochains are synthesized with diameters of 150-250 nm and lengths of 0.5-2
      microm by assembly of small nanoparticles, which exhibit a magnetic coercivity
      over two orders of magnitude larger than that of bulk Ni.

PMID- 15568088
TI  - Synthesis and photocleavage of a new dimeric bis(o-nitrobenzyl) diether tether.
AB  - A new photocleavable linker, 4,4'-bis(alkoxymethyl-3,3'-dinitro)biphenyl, is
      reported that undergoes photolysis at two positions to release two equivalents of
      primary, secondary, or benzylic alcohol in yields that are higher than those
      obtained from the analogous monomeric o-nitrobenzyl ethers.

PMID- 15568089
TI  - Thermally stable macroporous zirconium phosphates with supermicroporous walls: a
      self-formation phenomenon of hierarchy.
AB  - A self-formation phenomenon leading to the hierarchically thermally stable
      macroporous zirconium phosphates with amorphous supermicroporous walls from the
      precursors of zirconium propoxide and orthophosphoric acid solution was observed.

PMID- 15568090
TI  - Dimerization of terminal alkynes catalyzed by a nickel complex having a bulky
      phosphine ligand.
AB  - Ni(cod)(2)/P(t)Bu(3) system catalyzed the dimerization of terminal alkynes to
      give (E)-head-to-head dimerization products, in which the stannylacetylene dimer
      could be applied to a one-pot synthesis of a conjugated enyne, when combined with
      Migita-Stille coupling.

PMID- 15568091
TI  - A (H2O)4/crown ether network spanned between organometallic complex metal
      fragments.
AB  - [Mo(eta3)-C3H5)(CO)2(bipy*)Cl] undergoes trigonal twist rearrangements in
      solution, so that three isomers are coexisting. It was used as a starting
      material leading to a dinuclear complex containing a hydrogen-bonded network of
      H(2)O and crown-ether molecules between two Mo(eta3-C3H5)(CO)2(bipy*) moieties.

PMID- 15568092
TI  - Chemical reactions of double bonds in activated carbon: microwave and bromination
      methods.
AB  - The reaction of localised C[double bond, length as m-dash]C bonds on the surface
      of activated carbons has been shown to be an effective method of chemical
      modification especially using microwave-assisted reactions.

PMID- 15568093
TI  - Bent metal carbene geometries in amido N-heterocyclic carbene complexes.
AB  - Lithium(I) and uranium(VI) amido-tethered Bu(t)-substituted N-heterocyclic
      carbene (NHC) complexes exhibit very distorted metal-carbene bonds; the
      corresponding magnesium(II) and mesityl-substituted NHC uranium(VI) complexes are
      undistorted; the distortion does not affect the ligand binding strength,
      suggesting a dominance of electrostatic character in closed-shell electropositive
      metal-carbene bonds.

PMID- 15568094
TI  - Chiral recognition by proton transfer reactions with optically active amines and
      alcohols.
AB  - A simple, rapid tandem mass spectrometric method for recognition of chiral
      molecules by proton transfer reactions with chiral sec-butylamines and sec
      butanols is reported.

PMID- 15568095
TI  - A first oxalamidino complex of samarium via reduction-coupling of carbodiimine:
      synthesis and molecular structure of [eta4-C2(NR)4][(MeC5H4)2Sm(HMPA)]2.2THF (R =
      Pr i, Cy).
AB  - Treatment of the THF solution of (MeC5H4)2Sm(THF) with an equivalent of
      carbodiimine [RN=C=NR](R = Pr(i) or Cy; Cy = cyclohexyl) in the presence of an
      equivalent of hexamethylphosphoric triamide (HMPA) at room temperature gives, via
      a reduction-coupling reaction of carbodiimine, the corresponding bimetallic
      oxalamidino complex of samarium [eta4-C2(NR)4][(MeC5H4)2Sm(HMPA)]2.2THF.

PMID- 15568096
TI  - Enhanced fluorescence quenching in receptor-containing conjugated polymers: a
      calix[4]arene-containing poly(phenylene ethynylene).
AB  - A fluorescent poly(phenylene ethynylene) containing calix[4]arene-based receptor
      units has a sensitivity to quenching by the N-methylquinolinium ion that is over
      three times larger than that seen in a control polymer lacking calix[4]arenes.

PMID- 15568097
TI  - Biomimetic thermo-responsive star diblock gelators.
AB  - We report the synthesis of novel biomimetic gelators with star diblock copolymer
      architectures by sequential monomer addition via alcoholic ATRP at 20 degrees C;
      free-standing gels can be formed from 5% aqueous copolymer solutions at 37
      degrees C.

PMID- 15568098
TI  - Mechanism of hydrogen transfer to imines from a hydroxycyclopentadienyl ruthenium
      hydride. Support for a stepwise mechanism.
AB  - The negligible double kinetic deuterium isotope effect (k(HH)/k(DD)= 1.05) in the
      reaction where [2,3,4,5-Ph4(eta5-C4COH)Ru(CO)2H (2) transfers a hydride and a
      proton to N-phenyl-[1-(4-methoxyphenyl)ethylidene]amine (4) indicates that no
      bond to hydrogen is broken or formed in the rate-determining step.

PMID- 15568099
TI  - Liquid poly(ethylene glycol) and supercritical carbon dioxide as a biphasic
      solvent system for lipase-catalyzed esterification.
AB  - The biphasic solvent system composed of poly(ethylene glycol)(PEG) and
      supercritical carbon dioxide (scCO2) is ideally suited for the lipase-catalyzed
      acylation of alcohols; batch or continuous flow acylations are possible, scCO2
      being used to extract the products.

PMID- 15568100
TI  - A p-phosphinophenolate ligand for the palladium-catalysed arylation of alkenes.
AB  - A triphenylphosphine having a strong electron-donating group, an oxyanion, at the
      para position of one of the benzene rings was found to show much higher
      efficiency compared with other structurally related triarylphosphines in the
      palladium-catalysed arylation of alkenes.

PMID- 15568101
TI  - Electrodeposition of monodispersed Fe nanocrystals from an ionic liquid.
AB  - Monodispersed Fe nanocrystals up to approximately 2 nm thick, approximately 50 nm
      wide and approximately 120 nm long have been electrodeposited from the ionic melt
      AlCl(3)-1-methyl-3-butylimidazolium chloride [AlCl3-[MBIm](+)Cl(-)] at room
      temperature on Au(111) and have been characterized in-situ by electrochemical
      scanning tunneling microscopy.

PMID- 15568102
TI  - Polystyryl-supported TBD as an efficient and reusable catalyst under solvent-free
      conditions.
AB  - Polystyryl supported-TBD (PSTBD) is an efficient and reusable heterogeneous basic
      catalyst under solvent-free conditions for a variety of organic transformations
      such as 1,2-epoxide ring-opening, aldol-type condensation and Michael addition.

PMID- 15568103
TI  - Self-assembled zinc(II) Schiff base polymers for applications in polymer light
      emitting devices.
AB  - Thermally stable zinc(II) Schiff base polymers (decomposition temperature up to
      461 degrees C; M(n)= 13580 to 20440) formed by self-assembly reactions of
      zinc(II) salts and salicylaldimine monomers exhibit blue to yellow PL with
      quantum yields up to 0.34 in DMF; PLEDs employing these polymers as emitters give
      green or orange EL with turn-on voltage at 5 and 6 V and maximum efficiency of
      2.0 and 2.6 cd A(-1) respectively.

PMID- 15568104
TI  - Selective synthesis of isomeric heterodinuclear complexes with switched metal
      arrangements via proton-induced reversible metal migration.
AB  - Pairs of isomeric heterodinuclear complexes, [(cod)Ir(mu-PNNN)M(L)]BF4 and
      [(L)M(mu-PNNN)Ir(cod)]BF4, with switched metal arrangements are prepared in a
      specific manner by simply changing the addition order of the reagents.

PMID- 15568105
TI  - Preparation of ordered large pore SBA-15 silica functionalized with aminopropyl
      groups through one-pot synthesis.
AB  - Highly ordered large pore SBA-15 silica functionalized with up to 16% aminopropyl
      groups, which gave high catalytic activity and selectivity toward flavanone
      synthesis through aldol condensation and subsequent intramolecular Michael
      addition of benzaldehyde and 2'-hydroxyacetophenone, was synthesized for the
      first time via co-condensation of tetraethylorthosilicate (TEOS) and 3
      aminopropyltriethoxysilane (APTES) using an amphiphilic block copolymer as the
      structure-directing agent.

PMID- 15568106
TI  - Adduct formation by photo-induced electron transfer between photo-oxidising
      Ru(II) complexes and tryptophan.
AB  - The (3)MLCT excited state of Ru(II) complexes with 1,4,5,8-tetraazaphenanthrene
      (TAP) ligands in the presence of tryptophan gives rise to an electron transfer
      process from the amino acid with subsequent formation of an adduct between the
      two partners, strongly influenced by oxygen.

PMID- 15568107
TI  - Spherical carbon capsules with hollow macroporous core and mesoporous shell
      structures as a highly efficient catalyst support in the direct methanol fuel
      cell.
AB  - Carbon capsules with hollow core and mesoporous shell (HCMS) structures were used
      as a support material for Pt(50)-Ru(50) catalyst, and the catalytic performance
      of the HCMS supported catalyst in the direct methanol fuel cell was described;
      the HCMS carbon supported catalysts exhibited much higher specific activity for
      methanol oxidation than the commonly used E-TEK catalyst by about 80%, proving
      that the HCMS carbon capsules are an excellent support for electrode catalysts in
      DMFC.

PMID- 15568108
TI  - Cu+(H2) and Na+(H2) adducts in exchanged ZSM-5 zeolites.
AB  - Cu(I) ions in Cu-ZSM-5 form Cu+(H2) complexes, stable at room temperature and sub
      atmospheric H2 pressure, which do not have any homogeneous analogue except for
      matrix-isolated [Cu(eta2-H2)Cl]. Comparison with the unstable Na+(H2) adducts
      formed in the parent Na-ZSM-5 zeolite allow the conclusion that the Cu(I)/H2 bond
      is governed by sigma-pi overlap forces.

PMID- 15568109
TI  - First example of chiral N-heterocyclic carbenes as catalysts for kinetic
      resolution.
AB  - Chiral N-heterocyclic carbenes, which are derived from C2-symmetric 1,3-bis(1
      arylethyl)imidazolium salts, catalyze enantioselective acylation of racemic
      secondary alcohols.

PMID- 15568110
TI  - Micro-particle sorting by Newton-ring device.
AB  - A Newton-ring micro-particle sorter was constructed from a small convex lens and
      a flat glass. The sub-micrometer gap between them was controlled by a piezo
      actuator and utilized for the fractionation of very small amounts of micro
      particles in liquid.

PMID- 15568111
TI  - Low temperature 1,1,1-trichloroethane dehydrochlorination over Pt catalysts: from
      model surfaces to the real world.
AB  - Fast X-ray photoelectron spectroscopy reveals efficient C-Cl activation of 1,1,1
      trichloroethane occurs over platinum surfaces at 150 K, and in the presence of
      hydrogen, sustained ambient temperature dehydrochlorination to HCl and ethane is
      possible over supported Pt/Al2O3 catalysts.

PMID- 15568112
TI  - An improved palladium-based DMFCs cathode catalyst.
AB  - A novel carbon-supported palladium-rich Pd3Pt1/C catalyst prepared by a modified
      polyol process showed a better cell performance than Pt/C in direct methanol fuel
      cells, which may be attributed to palladium's inactivity to methanol electro
      oxidation while exhibiting good performance to oxygen reduction reaction.

PMID- 15568113
TI  - Asymmetric synthesis of 2-alkyl- and 2-aryl-3-aminopropionic acids (beta2-amino
      acids) from (S)-N-acryloyl-5,5-dimethyloxazolidin-2-one SuperQuat derivatives.
AB  - Conjugate addition of lithium amides to (S)-N-acryloyl- or (S)-N-2'
      alkylacryloyloxazolidinones and alkylation or protonation of the resulting
      enolates with 2-pyridone respectively provides a highly stereoselective and
      product complementary route to a range of (R)- and (S)-2-alkyl-3-aminopropionic
      acids in good yield and in high ee.

PMID- 15568114
TI  - How hard should we look for the evidence?

PMID- 15568115
TI  - Professional development--in a changing world.

PMID- 15568116
TI  - Biostatistics 302. Principal component and factor analysis.

PMID- 15568117
TI  - Finding the evidence: resources and skills for locating information on clinical
      effectiveness.
AB  - Limited time and lack of knowledge about where and how to search for information
      often present barriers to practitioners who want to locate current best evidence
      for treating their patients. There is as yet no single place they can go to get
      an answer to all their questions. High quality clinical studies are difficult to
      filter out from the mass of information on large databases, and secondary
      resources of evaluated information are dispersed over hundreds of Internet sites
      worldwide. This overview presents a practical guide for the busy practitioner who
      searches only occasionally and needs to maximise the time spent. Major
      collections of secondary resources are identified and their individual features
      described briefly. Following this, several services using PubMed are outlined
      that automatically apply filters for studies with high quality research design.
      Further sources of information and assistance are listed for those who wish to
      learn more.

PMID- 15568118
TI  - Adverse drug reactions in Singaporean children.
AB  - INTRODUCTION: Allergic reactions to drugs are considered rare in the paediatric
      population. Host genetic and environmental factors influence the reported
      incidence and characteristics of adverse drug reactions (ADRs), and cause
      significant variation according to the population described and case definition
      used. We aimed to define the prevalence and characteristics of reported drug
      allergies in hospitalised children in Singapore. METHODS: A retrospective case
      control study was performed through the hospital's inpatient electronic medical
      record (EMR) for the period of August 2002 to December 2002. The EMR was used to
      identify children with a previously reported ADR. The control group was randomly
      selected from patients hospitalised during the same period. RESULTS: Of the 8437
      patients hospitalised during the study period, reports of previous ADRs were
      found in the records of 222 patients. The mean age of the patients was 7.4 years,
      range 2 months to 17 years (95 percent confidence interval [CI] 6.3 - 8.4). There
      were 146 males and 160 Chinese. The most commonly-involved medications were
      betalactam antibiotics (45 percent) and non steroidal anti-inflammatory drug
      (18.5 percent). Compared to the control group, children with a reported ADR were
      more likely to be older, with a mean age of 7.4 years versus 4.6 years (p-value
      less than 0.001), male (odds ratio [OR] 1.7, 95 percent CI 1.2-2.4), of Chinese
      descent (OR 1.8, 95 percent CI 1.5-5), have an associated chronic illness (OR
      3.5, 95 percent CI 2.5-5), and a diagnosis of asthma (OR 2.7, 95 percent CI 1.7
      4.5). CONCLUSION: In our paediatric inpatient population, the risk of reported
      ADRs increases with age, male gender, Chinese descent and the presence of chronic
      disease. The major drugs involved are betalactam antibiotics and non-steroidal
      anti inflammatory drugs.

PMID- 15568119
TI  - Breath carbon monoxide as an indication of smoking habit in the military setting.
AB  - INTRODUCTION: The breath carbon monoxide (CO) monitor has been shown to be an
      effective tool in predicting smoking habits. This study aims to assess whether
      the breath CO level can be employed to determine a person's smoking habit in the
      military setting and to analyse various factors that can influence the breath CO
      levels. METHODS: 155 navy personnel were questioned on their smoking habits in
      phase one of the study. The subjects were explained the objective of the study
      and instructed to provide two breaths into the CO monitor (EC-50 Smokerlyser,
      Bedford Instruments, Kent, UK). In a subsequent single blind study, 40 trainees
      were not told of the purpose of the study and were assessed via a questionnaire
      and smokerlyser estimation. Descriptive statistics were used to examine the data
      and assess distribution. Depending on the distribution, a two-sample t test or
      Mann-Whitney U test were used to test for a significant difference between CO
      levels among smokers and non-smokers. RESULTS: In phase one, the mean breath CO
      levels were 11.6 (plus or minus 6.2) ppm for smokers and (1.9 plus or minus 0.9)
      ppm for non-smokers (p-value less than 0.0001). A cut-off level of 5 ppm gave a
      sensitivity of 96 percent and a specificity of 98 percent. The high CO levels
      were clustered within five hours of the last cigarette smoked. Therefore, this
      value may not reliably predict smoking habits if an individual smoked more than
      five hours before the test. Of the 40 subjects in phase two, five smokers who
      stated that their last cigarette smoked was 48 hours before the breath test had a
      mean CO level greater than 5 ppm. (range of 5.5 to 18.0 ppm). On further
      questioning, all admitted to having smoked on the day of the test. CONCLUSION:
      The breath CO monitor has good potential for use as an adjunct in future smoking
      control assessments and a reading greater than 5 ppm strongly suggests that the
      military outpatient is a smoker.

PMID- 15568120
TI  - A survey of fasting during pregnancy.
AB  - INTRODUCTION: Fasting during the month of Ramadan is compulsory in the Muslim
      faith. Although pregnant women may be exempted, many still choose to fast while
      others are more careful in practising it. This survey examines the practice of
      fasting among pregnant Muslim women in Singapore based on the prevalence in
      relation to factors such as parity, social and economic circumstances. It also
      analyses the factors that influence the decision to fast and the successful
      completion of the fast, and examines their knowledge, belief and attitudes on
      fasting during the holy month of Ramadan. METHODS: This is a retrospective study
      of all Muslim women who were pregnant and received antenatal care in our hospital
      during the month of Ramadan from 17 November 2001 to 16 December 2001. A four
      page questionnaire was mailed to all eligible subjects in March 2002. RESULTS: Of
      202 eligible subjects, 125 responded via mail and 57 via the phone, yielding a
      response rate of 90 percent. Most women chose to fast during pregnancy, and they
      do so with adequate support from their spouses and family members. Most of them
      do not experience any adversities during fasting and even if they do, most were
      able to overcome them. Most women adopt a positive attitude towards fasting.
      However, there is a lack of basic religious knowledge among many pregnant women
      pertaining to the Muslim law of fasting during pregnancy. CONCLUSION: Doctors and
      health workers need to understand the religious obligations of a Muslim towards
      fasting during Ramadan. Only through this can a doctor adequately counsel Muslim
      patients and allow informed decision with regards to fasting. With respect to
      pregnant women, provisions are allowed for them not to observe fasting.

PMID- 15568121
TI  - Medical students' behaviour, attitudes and knowledge of sleep medicine.
AB  - INTRODUCTION: A seminar on sleep disorders was recently introduced for third,
      fourth and final year medical students rotating through the psychiatry posting in
      the Institute of Mental Health. This survey was conducted to assess the attitudes
      as well as knowledge of medical students towards sleep medicine. METHODS: Verbal
      consent was taken from the students who were willing to take part in the survey.
      The MED Sleep Survey, which is an inventory to assess behavior, attitudes and
      knowledge about sleep, was used to assess the same in the students. RESULTS: A
      total of 240 medical students completed the survey. There were 149 male and 91
      female medical students. In terms of their basic sleep knowledge, 46.7 percent
      scored between 1 and 10 points, 51.7 percent scored between 11 and 20 points, and
      1.7 percent scored between 21 and 30 points. There was no significant difference
      between the different groups in their scores on basic sleep knowledge.
      CONCLUSION: Most of the medical students scored between 1 and 20 points on basic
      sleep knowledge items in part III of the survey. Of these, almost one-half had
      scores between 1 and 10 points. Education is clearly important, and the
      introduction of the teaching programme on sleep medicine is timely and necessary.

PMID- 15568122
TI  - Previously-treated nasopharyngeal carcinoma with cystic lesions in the temporal
      lobe.
AB  - Nasopharyngeal carcinoma is a common malignancy in the Asian Chinese population.
      First-line treatment consists primarily of radiotherapy and chemotherapy, with
      salvage surgery if recurrence occurs. Patients with this tumours frequently
      present years after radiotherapy with symptomatic temporal lobe cystic lesions
      and a diagnostic problem arises. The possible differential diagnoses include
      radionecrosis, pyogenic abscesses or tumour recurrence. A series of three cases
      of cystic temporal lobe lesions, with emphasis on their clinical, radiological
      and histopathological diagnostic aspects, are presented. The three cases
      presented consist of radiation necrosis, pyogenic abscess, and a case with both
      infection with tumour recurrence. The methodology of both clinical and
      radiological diagnosis are presented.

PMID- 15568123
TI  - Fibrinolysis of loculated pleural effusion in malignant mesothelioma.
AB  - Surgical resection is not feasible in most cases of malignant mesothelioma and
      palliation of symptoms remains the mainstay of treatment. When a pleural effusion
      is loculated, the standard treatment methods of intercostal tube drainage and
      pleurodesis may not be helpful. We report a 49-year-old man with malignant
      mesothelioma in whom intrapleural fibrinolysis was performed using streptokinase.
      It was successful in breaking the locules and draining the effusion. Intrapleural
      fibrinolysis should be considered in cases of loculated pleural effusion due to
      malignant mesothelioma, as it may provide symptom relief and palliation.

PMID- 15568129
TI  - [Particle pollution and allergies in children. What relationships are found in
      epidemiological studies?].
AB  - Particles in the air influence mortality and morbidity even in concentrations
      which were considered harmless. This report examines their role in allergies.
      Studies on children from areas with different degrees of pollution show that the
      "classical" type of air pollution with high amounts of coarse particles
      apparently does not induce allergies. Nearly all studies, which characterized
      exposure on a smaller spatial scale, found that symptoms of asthma and allergic
      rhinitis were more common in children exposed to traffic-related pollution. Time
      series and panel studies demonstrate that particle pollution contributes to
      asthma aggravation. Whether this applies to eczema or allergic rhinitis has
      hardly been investigated. Overall the studies suggest a special role for traffic
      related particles.

PMID- 15568128
TI  - [Trauma surgery in the elderly].
AB  - The indications for the surgical treatment of fractures in elderly patients
      should consider the individual's general health status, the specific pattern of
      injury, and the ability of the patient to actively participate in the
      rehabilitation process. Intramedullary systems are the gold standard for shaft
      and metaphyseal fractures due to the decreased operative trauma and the
      possibility of early weight bearing and functional treatment. Minimally invasive
      locking plate systems can frequently be applied, offer decreased risk of
      secondary fracture displacement, and have great advantages in the treatment of
      periprosthetic fractures with firm implants. The possible reasons for falls
      should be diagnosed in order to allow their prevention. An exact assessment of
      the severity of osteoporosis in important in allowing adequate treatment for
      associated pain and for decreasing the risk of future osteoporosis related
      fractures.

PMID- 15568130
TI  - [Penetration of microparticles into human skin].
AB  - The efficacy of the penetration of microparticles into the human skin depends on
      the size and the type of the formulation with which they are topically applied.
      Microparticles with a diameter of >1 microm barely penetrate into the human skin.
      They are located on the skin surface and form a film which, for instance, can be
      used for camouflage or protection against UV radiation in sunscreens. While the
      penetration of the microparticles in the lipid layers of the stratum corneum is
      limited, they penetrate efficiently into the hair follicles up to a depth >2 mm,
      providing their diameter is <1.5 microm. Thus, microparticles can be used for
      drug delivery into the hair follicles.

PMID- 15568131
TI  - [The effect of low molecular weight substances on the human skin. Molecular
      mechanisms and their consequences].
AB  - Interactions between low molecular weight compounds with cells of the skin result
      in reactions with different proteins which enable the uptake, metabolism and
      efflux of these compounds. It is unlikely, that small molecular weight compounds
      can achieve pharmacological concentrations within cells by diffusion alone. The
      pattern of influx proteins of keratinocytes is different from that of
      hepatocytes. If the balance between these systems is disturbed, the skin may
      become unable to function as a protective organ which can result in diseases
      including cancer or-more frequently-allergic contact dermatitis. Recent
      investigations of the sensitization to fragrances and p-phenylenediamine are
      discussed. An improved understanding of the metabolism of low molecular weight
      compounds can lead to new therapeutic strategies. One example is the introduction
      of photodynamic therapy with topical applied porphyrin precursors.

PMID- 15568132
TI  - [Treatment of therapy-resistant acral ulcers with iloprost].
AB  - Patients with systemic sclerosis (SSc) develop often acral ulcers which are
      resistant to therapy and may result in gangrene and amputation. We investigated
      the effects of iloprost infusion on the acral ulcers and necrosis in patients
      with five patients with SSc and one with mixed connective tissue disease who had
      been previously treated with various modalities without improvement. All patients
      had Raynaud phenomenon, acral ulcers and necrosis. Iloprost 25 microg per day was
      administered intravenously daily over six hours for ten consecutive days. Eight
      weeks later all patients were treated with a second iloprost therapy cycle for
      five days. Two patients with severe ulceration received a third cycle until
      remission occurred. In all cases acral ulcers healed completely and no patient
      relapsed during an observation period of 6 months.

PMID- 15568133
TI  - [Stigmatization. Consideration from a theological-dermatologic perspective].
AB  - Stigmatization is associated with considerable psychosocial impairment. Patients
      with chronic skin disease are especially prone to stigmatization and reduced
      quality of life. In contrast, patients with self-produced cutaneous artifacts
      receive an emotional response from family members and doctors. Stigmatization of
      a religious nature is always difficult for non-participants to understand. We
      focus on the suffering of the patient, using the example of a historical person,
      Saint Rita of Cascia, who bore a stigma on her forehead. We discuss why suffering
      is presented in this manner, and how salvation can be the positive effect of
      suffering.

PMID- 15568134
TI  - ["The fungal jungle". Medical mycology on the Internet].
AB  - The World Wide Web offers an enormous variety of information about medical
      mycology. To go through the "fungal jungle" and find the website containing the
      information that is needed requires a great deal of effort and a lot of time.
      This article provides help in finding information about medical mycology and
      describes the contents of preselected websites in German and English. These pages
      address physicians, scientists, and students interested in dermato-mycology. Most
      of the pages also contain information about mycoses relevant to other medical
      specialties.

PMID- 15568135
TI  - Osteoclastic cortical erosion as a determinant of subperiosteal osteoblastic bone
      formation in the femoral neck's response to BMU imbalance. Effects of stance
      related loading and hip fracture.
AB  - Femoral neck fractures have previously been shown to be associated with increased
      cortical and endocortical remodeling, reduced wall thickness of endocortical
      packets and cortical porosity. Femoral neck width is associated positively with
      history of lifetime physical activity; so we hypothesized that exposure to
      mechanical loading may influence the subperiosteal osteoblastic response to the
      weakening effect of intracortical bone resorption. In 21 femoral neck biopsies
      from female subjects (13 with hip fracture), there was a positive association
      between osteoblastic periosteal alkaline phosphatase expression shown in frozen
      sections and the percentage of cortical canals internal to the subperiosteal
      surface showing evidence of osteoclastic erosion (Goldner's stain; p =0.03). This
      was stronger in the plane of locomotor loading and particularly strong in the
      inferior (compression) cortex ( p =0.002). In 35 cases and 23 age/gender-matched
      postmortem controls, osteoid-bearing cortical canals (%) were significantly
      elevated in the fracture cases compared with the controls within the anterior
      region. There was also a significant correlation between cortical and
      endocortical %OS/BS (percentage osteoid surface to bone surface) (fracture, n
      =12; control, n =12) over the whole biopsy ( p =0.041). Generally, these
      associations of intracortical with endocortical remodeling were consistent with
      both envelopes being regulated by common processes. These results support the
      concept that the slow growth of femoral neck width by subperiosteal apposition of
      bone occurs directly or, otherwise, in response to the weakening of the cortex as
      it is "trabecularized" by imbalance of bone multicellular units (BMU). This
      process, in turn, depends on cortical thinning and enlargement of canals with the
      formation of giant, composite osteons, the whole being more marked in cases of
      future hip fracture.

PMID- 15568136
TI  - Multivariate analysis to separate the signal given by cross-reactants in
      immunoassay with sample matrix dilution.
AB  - This paper describes a new approach to achieve selectivity in an immunoassay by
      separating the signals given by two cross-reactive compounds present
      simultaneously in a complex sample matrix. The method is based on the sequential
      dilution of the sample containing a mixture of the two analytes, spiking each
      diluted sample with a reference compound, and the detection by enzyme-linked
      immunosorbent assay (ELISA). The obtained multivariate response was used for the
      individual calibrations of the assay for each of the two cross-reactants
      simultaneously by using principal component analysis (PCA) and partial least
      squares regression (PLSR) data modeling. The calibration models showed that the
      signal separation due the analytes 2,4-dinitrophenol (2,4-DNP) and 4-nitrophenol
      (4-NP) was possible with a prediction concentration error of 1.4 microM and 72
      microM, respectively.

PMID- 15568137
TI  - The need for new SI-traceable magnesium isotopic reference materials.
AB  - Recent measurements revealed that commercial magnesium standard solutions showed
      isotopic abundance variations, which cannot clearly be distinguished from each
      other by calibrating against the only available isotopic reference material, SRM
      980, or reference materials made from SRM 980 like IRMM-009. Therefore new SI
      traceable magnesium isotopic reference materials are required.

PMID- 15568138
TI  - Polystyrene film-coated glassware: a new means of reducing metal losses in trace
      metal speciation.
AB  - A recently developed process for coating a glass surface with polystyrene (PS)
      film, by use of a simple chemical process has been used to reduce trace metal
      adsorption by cell components. The glass coating is a two-step procedure
      consisting of covalent attachment of vinyl-terminated PS to Si atoms on the glass
      surface then adsorption of PS from solution to create a stable PS film. To assess
      the quality of the coating we used anodic stripping voltammetry to study the
      adsorption of lead and cadmium ions in coated and untreated glass cells. In both
      short and long-term (24 h) experiments we observed that the amount of metal
      adsorbed was considerably less for the PS film-coated glass cell than for the
      uncoated cell. Further experiments showed that metal desorption is faster and
      metal contamination after cleaning is significantly lower for the coated cells.
      The PS film was, moreover, stable over a period of 6 months within the pH range
      3.5-9.

PMID- 15568139
TI  - Determination of pipemidic acid based on flow-injection chemiluminescence due to
      energy transfer from peroxynitrous acid synthesized on-line.
AB  - A flow-injection chemiluminescence (CL) method for the determination of pipemidic
      acid is described. It is based on energy transfer from excited state
      peroxynitrous acid to pipemidic acid, in which the excited state peroxynitrous
      acid is synthesized on-line by the mixing of acid hydrogen peroxide with nitrite
      in a flow system and the CL is from two excited states of pipemidic acid. The
      proposed method allows the measurement of pipemidic acid over the range of 2.0 x
      10(-7)-2.0 x 10(-5) mol l(-1) . The detection limit is 6.3 x 10(-8) mol l(-1),
      and the relative standard deviation for 2.0 x 10(-6) mol l(-1) pipemidic acid (n
      = 9) is 0.9%. This method was evaluated by the analysis of pipemidic acid in
      pharmaceutical preparations.

PMID- 15568140
TI  - The majority of hospitalised patients have drug-related problems: results from a
      prospective study in general hospitals.
AB  - OBJECTIVE: To describe the frequency and types of drug-related problems (DRPs) in
      hospitalised patients, and to identify risk factors for DRPs and the drugs most
      frequently causing them. METHODS: From May to December 2002, 827 patients from
      six internal medicine and two rheumatology departments in five hospitals in
      Norway were included in this study. We recorded demographic data, drugs used,
      relevant medical history, laboratory data and clinical/pharmacological risk
      factors, i.e. reduced renal function, reduced liver function, heart failure,
      diabetes, compliance problems, drugs with a narrow therapeutic index and drug
      allergy. DRPs were documented after reviewing medical records and participation
      in multidisciplinary team discussions. An independent quality assessment team
      retrospectively assessed the DRPs in a randomly selected number of the study
      population. RESULTS: Of the patients, 81% had DRPs, and an average of 2.1
      clinically relevant DRPs was recorded per patient. The DRPs most frequently
      recorded were dose-related problems (35.1% of the patients) followed by need for
      laboratory tests (21.6%), non-optimal drugs (21.4%), need for additional drugs
      (19.7%), unnecessary drugs (16.7%) and medical chart errors (16.3%). The patients
      used an average of 4.6 drugs at admission. A multivariate analysis showed that
      the number of drugs at admission and the number of clinical/pharmacological risk
      factors were both independent risk factors for the occurrence of DRPs, whereas
      age and gender were not. The drugs most frequently causing a DRP were warfarin,
      digitoxin and prednisolone, with calculated risk ratios 0.48, 0.42 and 0.26,
      respectively. The drug groups causing most DRPs were B01A-antithrombotic agents,
      M01A-non-steroidal anti-inflammatory agents, N02A-opioids and C09A-angiotensin
      converting enzyme inhibitors, with risk ratios of 0.22, 0.49, 0.21 and 0.35,
      respectively. CONCLUSIONS: The majority of hospitalised patients in our study had
      DRPs. The number of drugs used and the number of clinical/pharmacological risk
      factors significantly and independently influenced the risk for DRPs. Procedures
      for identification of, and intervention on, actual and potential DRPs, along with
      awareness of drugs carrying a high risk for DRPs, are important elements of drug
      therapy and may contribute to diminishing drug-related morbidity and mortality.

PMID- 15568141
TI  - The effects of acute ethanol intake on isoniazid pharmacokinetics.
AB  - AIM: To assess effects of acute ethanol intake on the pharmacokinetics of
      isoniazid in healthy male volunteers. METHODS: Sixteen healthy male, drug-free
      subjects were studied. Each received in the fasting state, on two occasions
      separated by at least 1 week, isoniazid (200 mg orally). On one occasion
      (assigned randomly), subjects received ethanol 0.73 g/kg, 1 h before isoniazid,
      followed by 0.11 g/kg ethanol orally every hour thereafter for 7 h. Plasma
      isoniazid and acetylisoniazid concentrations were measured by means of high
      performance liquid chromatography. Blood ethanol concentrations were measured
      hourly by breath analysis. Plasma concentrations of isoniazid and acetylisoniazid
      were analysed using TOPFIT software. RESULTS: Peak concentrations of isoniazid
      were reached within 90 min, in both the ethanol-treated and control groups. The
      ethanol dosage regimen used resulted in peak blood ethanol concentrations between
      78 mg/l and 103 mg/l. There was no significant difference in area under the
      curve, half-life of elimination or the ratio of acetylisoniazid to isoniazid
      (AcINH/INH) in the sample withdrawn 3 h after isoniazid dose. Acetylator
      phenotype for patients was the same in both phases, whether assessed by half-life
      of isoniazid or the AcINH/INH ratio at 3 h. CONCLUSIONS: Acute ethanol intake at
      this dose is unlikely to affect results of acetylation studies in which isoniazid
      is used as a substrate, whether the half-life of isoniazid or the AcINH /INH
      ratio at 3 h is used to phenotype patients.

PMID- 15568142
TI  - Central nervous system toxicity following topical skin application of lidocaine.

PMID- 15568143
TI  - Frequency modulation patterns in the echolocation signals of two vespertilionid
      bats.
AB  - In this study we measure and classify frequency modulation patterns in
      echolocation signals of two species of bats. By using the derivative of an
      exponential model fitted to pulses emitted by Pipistrellus pipistrellus and
      Myotis myotis, we show that the modulation functions differ fundamentally between
      the two species and also vary within each species. This variation makes it
      unlikely that pulse design and the concomitant modulation pattern can be
      explained by a single common principle as previously suggested.

PMID- 15568144
TI  - Socks for the dilated heart. Does passive cardiomyoplasty have a role in long
      term care for heart failure patients?
AB  - Dynamic cardiomyoplasty has been performed in over 1000 patients worldwide but
      due to limited success the procedure was never been adopted as an alternative
      approach for the surgical therapy of heart failure. However, observations in
      these patients showed that the nonstimulated or fibrotic transformed latissimus
      dorsi by itself led to an improvement of heart failure symptoms. These findings
      stimulated animal experiments with so-called passive cardiomyoplasty devices. In
      several animal models, the progression of heart failure could be stopped, and
      even reversed remodeling could be demonstrated. Several different devices have
      been developed and tested in animal models. The Acorn CorCap has already passed a
      successful clinical feasibility study. However, the final evaluation of two
      multicenter trials has to be awaited to assess the future role of this device in
      the treatment of heart failure.

PMID- 15568145
TI  - P-selectin in arterial thrombosis.
AB  - P-selectin is a transmembrane protein present in the alpha granules of platelets
      and the Weibel-Palade bodies of endothelial cells. Following activation, it is
      rapidly translocated to the cell surface. P-selectin expression in platelets has
      been shown to be elevated in disorders associated with arterial thrombosis such
      as coronary artery disease, acute myocardial infarction, stroke, and peripheral
      artery disease. P-selectin mediates rolling of platelets and leukocytes on
      activated endothelial cells as well as interactions of platelets with leukocytes.
      Platelet P-selectin interacts with P-selectin glycoprotein ligand-1 (PSGL-1) on
      leukocytes to form platelet-leukocyte aggregates. Furthermore, this interaction
      of P-selectin with PSGL-1 induces the upregulation of tissue factor, several
      cytokines in leukocytes and the production of procoagulant microparticles,
      thereby contributing to a prothrombotic state. P-selectin is also involved in
      platelet-platelet interactions, i. e. platelet aggregation which is a major
      factor in arterial thrombosis. P-selectin interacts with platelet sulfatides,
      thereby stabilizing initial platelet aggregates formed by GPIIb/IIIa-fibrinogen
      bridges. Inhibtion of the P-selectin-sulfatide interaction leads to a reversal of
      platelet aggregation. Thus, P-selectin plays a significant role in platelet
      aggregation and platelet- leukocyte interactions, both important mechanisms in
      the development of arterial thrombosis.

PMID- 15568146
TI  - [Molecular biology of the heart atrium. New insights into the pathophysiology of
      atrial fibrillation as well as its clinical implications].
AB  - Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the
      most important factors for embolic stroke. In recent years, a tremendous amount
      has been learned about the pathophysiology and molecular biology of AF. Thus,
      pharmacologic interference with specific signal transduction pathways appears
      promising as a novel antiarrhythmic approach to maintain sinus rhythm and to
      prevent atrial clot formation. This review highlights the underlying molecular
      biology of atrial fibrillation, which may also be relevant for AF therapy.

PMID- 15568147
TI  - Double thoracic artery--halved mid-term mortality? A 5-year follow-up of 716
      patients receiving bilateral ITA versus 662 patients with single ITA.
AB  - The superior patency of ITA grafts to saphenous veins is conclusive. The aim of
      the study was to collate mid-term benefit between patients receiving bilateral
      ITA (BITA) or single ITA (SITA). Outcome of 1378 pts with isolated CABG operated
      between 1/97-8/99 was analyzed retrospectively. Follow-up was 4.0 to 6.6 years
      (average 5.3). A total of 716 pts received BITA, 662 SITA and additional
      saphenous veins. We evaluated mortality rate, freedom from reoperation,
      intervention (PTCA/stent), and incidence of cardiac events and quality of life
      with respect to pts risk factors. Demographic data: Male gender was more frequent
      in both groups (BITA females: n=115; males: n=601; SITA females: n=150; males:
      n=512; p<0.01). Mean age was comparable in both groups with 69.2 years (42.7 to
      88.6 years) in the BITA group and 71.0 years (47.3 to 91.6 years) (n. s.) in the
      SITA group. RISK FACTORS: Incidence of diabetes mellitus (26.0 vs 25.9%) as well
      as the mean BMI (27.4 vs 27.0%) did not differ statistically in both groups.
      RESULTS: Clinical characteristics like NYHA/ CCS classifications showed a
      significant difference towards superior results only for stadium I in the BITA
      group. Mortality/cardiac events after 5.3 years average: Total mortality revealed
      5.2% (n=37) in the BITA vs 9.1% (n=60) in the SITA group (p</=0.005). The cardiac
      related mortality was 0.7% (n=5) in the BITA and 2.0% (n=13) in the SITA group
      (p<0.05). The non-cardiac-related mortality did not differ significantly (2.7 vs
      2.9%). The incidence of redo-operations was 0.1% (BITA) vs 0.6% (SITA) (n. s).
      Cardiac interventions like PTCA or stent were performed in 3.1% (BITA) vs 4.7%
      (SITA) or 3.7% (BITA) vs 4.2% (SITA) (n. s.) respectively. Infarction-rate was
      2.0% in the BITA and 3.0% in the SITA group (n. s.). CONCLUSIONS: Mid- to long
      term benefit of patients receiving bilateral ITA is superior to those with single
      ITA. Cardiac-related mortality and incidence of reoperation was reduced to less
      than half after BITA grafting. Freedom from cardiac interventions (PTCA/stent),
      NYHA/CCS classifications and quality of life were rarely influenced by BITA
      frequency.

PMID- 15568148
TI  - Incidence and time course of intimal plaque formation in the right coronary
      artery after radiofrequency current application detected by intracoronary
      ultrasound.
AB  - BACKGROUND: Despite the current clinical use of radiofrequency (RF) catheter
      ablation in infants and children, the late effects of RF current application at
      immature myocardium remain unclear. The purpose of this study was to investigate
      incidence and time course of coronary lesions after RF current application at
      developing myocardium in an animal model. RESULTS: In 10 pigs, 6 weeks of age
      (13+/-2 kg), RF current (500 kHz) was delivered by temperature guidance (75
      degrees C) using a steerable electrode catheter (4 mm tip electrode) over 30
      second periods. RF lesions were created at the lateral right atrial wall at the
      tricuspid valve annulus and the lateral left atrial and ventricular wall at the
      mitral valve annulus. Subsequent coronary angiography and intracoronary
      ultrasound (ICUS) of the right coronary artery (RCA) and the left circumflex
      artery (CX) were performed 3, 6, 9 and 12 months after RF current application.
      Quantitative coronary angiography did not exhibit any significant stenosis of the
      vessels during the study period. Intimal lesions of the RCA were documented for
      the first time at the 6-month study in 3 animals by ICUS (mean plaque area 2.2+/
      0.2 mm(2), mean area stenosis 30.4+/-4.0%). There was no significant change in
      lesion length, area stenosis and plaque area at the 9- and 12-month studies. All
      3 coronary artery lesions were confirmed in close proximity to myocardial RF
      lesions by histological examination 12 months after RF delivery. No intimal
      plaque formation of the CX was observed. CONCLUSIONS: Affection of the RCA as a
      late sequel after RF current application at the lateral right atrial wall
      occurred in 3 out of 8 long-term surviving pigs. Three to six months seem to be
      the time frame for the development of intimal lesions after RF delivery. In this
      experimental setting, angiography failed to detect these intimal changes. The
      potential risk of coronary affection may be important for catheter ablation
      procedures at the right atrial myocardium in infants and small children.

PMID- 15568149
TI  - Real-time myocardial contrast echocardiography for the detection of stress
      induced myocardial ischemia. Comparison with 99mTc-sestamibi single photon
      emission computed tomography.
AB  - BACKGROUND: Real-time contrast echocardiography (MCE) is a new promising
      technique for assessing myocardial perfusion. The purpose of this study was to
      test whether realtime MCE can be used to detect functionally significant coronary
      artery stenosis in patients with known or suspected coronary artery disease.
      Myocardial contrast echocardiographic studies were compared with nearly
      simultaneous 99mTc-sestamibi single photon emission computed tomography (SPECT)
      as a clinical standard reference to evaluate regional myocardial perfusion
      defects. METHODS: Real-time MCE based on continuous infusion of Optison (8-10
      ml/h) was performed in 66 patients during standard 99mTc-SPECT dipyridamole (0.56
      mg/kg x 4 min) stress testing. Images were obtained in apical 4- and 2-chamber
      views, each divided into 6 segments. Tracer uptake and myocardial opacification
      were visually analyzed for each segment by two pairs of blinded observers and
      graded as normal, mildly reduced, severely reduced, or absent. In 792 myocardial
      segments, myocardial opacification by MCE was uninterpretable in 143 (18%)
      segments and tracer uptake by SPECT was not clearly defined in 92 (12%) segments.
      Interobserver variability for MCE was good with concordance rates of 83%
      (kappa=0.72) for rest- and 86% (kappa=0.76) for stress images. Overall
      concordance between MCE and SPECT was good (83%, kappa=0.63) at a segmental
      level. In the diagnosis of fixed and reversible defects, and of normal perfusion,
      concordance rates were 73, 65 and 83%, respectively. When analysis was performed
      at the regional level, we found comparable levels of concordance rates for LAD
      (83%, kappa=0.59), LCX (86%, kappa=0.64) and RCA (80%, kappa=0.68) perfusion
      territories. CONCLUSIONS: These findings suggest that realtime MCE is a
      clinically acceptable method to evaluate myocardial perfusion defects during
      dipyridamole stress testing.

PMID- 15568150
TI  - [Mechanical complications of acute myocardial infarction].
AB  - Rupture of the left ventricular myocardium during the course of an acute
      myocardial infarction may affect the free wall, the interventricular septum, or
      the papillary muscles. When a rupture occurs, it is referred to as a mechanical
      complication of acute myocardial infarction. All mechanical complications may
      lead to cardiogenic shock. However, the location of the rupture can often be
      suspected clinically. To confirm the diagnosis, echocardiography must be
      performed. Since the advent of thrombolytic therapy and percutaneous coronary
      intervention, the incidence of mechanical complications has declined. Even though
      mortality remains high, their recognition is important since survivors may have
      an excellent long-term prognosis. The cases convey two main messages: 1)
      Mechanical complications must be carefully searched for in any patient with an
      acute coronary syndrome and signs of cardiogenic shock and/or a systolic murmur.
      2) Aggressive and timely medical and surgical treatment should be provided even
      though in a substantial proportion of these patients prognosis may be dismal.

PMID- 15568151
TI  - Perioperative hemodynamic measurements with an implantable monitoring system
      (Chronicle) in a patient with severe heart failure undergoing non-cardiac
      surgery.
AB  - A 53-year-old male patient with severe chronic heart failure due to ischemic
      cardiomyopathy (LVEF 25%) awaiting heart transplantation was admitted for
      resection of a bladder tumor. The patient underwent implantation of a Chronicle
      implantable hemodynamic monitor (IHM) two years before. Thus, perioperative
      monitoring of heart rate, right ventricular systolic, diastolic and pulse
      pressure, dP/dt and estimated pulmonary artery diastolic pressure through a lead
      implanted in the right ventricle was performed. In the postoperative period the
      patient developed low-output syndrome requiring catecholamine treatment. The
      patient was weaned from mechanical ventilation uneventfully the same day.
      However, he developed symptomatic and hemodynamic worsening of heart failure
      shortly after reduction of inotropes and required prolonged medical treatment
      with catecholamines. Patients with cardiac disease are known to be at increased
      risk for cardiovascular complications after noncardiac surgery. Therefore, it has
      been suggested that such patients could potentially benefit from perioperative
      invasive hemodynamic monitoring. For the first time, we report a case of
      perioperative continuous hemodynamic monitoring with a long term-implanted device
      in a potential heart transplant patient.

PMID- 15568153
TI  - [Prehospital accommodation of patients with acute coronary syndrome. Summary
      position paper of the German Society for Cardiological, Heart and Circulatory
      Research e.V. and the German Interdisciplinary Coalition for Intensive and
      Emergency Medicine].

PMID- 15568156
TI  - Epithelioid myoepithelioma of lacrimal gland.

PMID- 15568157
TI  - MUC1, MUC2 and MUC5AC expressions in cardiac myxoma.
AB  - BACKGROUND: Cardiac myxoma, the most common primary tumor of the heart, has a
      variable clinical presentation and immunohistochemical profile. An abundant
      mucopolysaccharidic matrix exists, including mucin, within cardiac myxoma. This
      investigation first reports the expressions of mucin genes in cardiac myxoma.
      METHODS: A retrospective study was conducted between December 1976 and February
      2003, comprising 101 consecutive patients with cardiac myxoma who were treated
      with surgical excision. Detailed clinical parameters also were reviewed. Mucin
      genes, namely MUC1, MUC2 and MUC5AC, were studied immunohistochemically in 47
      randomly selected patients. RESULTS: The study group contained 57 (57%) women and
      44 (43%) men, with a mean age of 38+/-21 years. Their presentations included:
      asymptomatic (41%), dyspnea (35%), stroke (23%), chest pain (7%), fever (6%),
      syncope (5%) and tricuspid regurgitation (70%). The sample included 90 myxoma
      located in the left atrium, 3 (3%) recurrent myxoma and 8 (8%) myxoma not located
      in the left atrium. The myxoma did not differ with location or clinical event in
      terms of pathological scores, such as vascular proliferation, inflammation,
      cellularity, hyaline, calcification and thrombosis. Cardiac myxoma is
      characterized by excessive mucus secretion. Expression of membrane-associated
      MUC1 was considerably higher than that of the secreted mucins, MUC2 and MUC5AC
      (P<0.05). Furthermore, expression of MUC5AC is related to lesser embolism
      (P<0.05). CONCLUSIONS: This work first examined the immunohistochemical
      expression of mucin (MUC1, MUC2 and MUC5AC) in cardiac myxoma. This investigation
      then showed that the expression of representative membrane-associated mucin,
      MUC1, and/or secretory mucins, MUC2 and MUC5AC, in cardiac myxoma was associated
      with important tumor clinicopathological characteristics. Moreover, MUC5AC
      appears related to lesser embolism. This approach can help distinguish the
      potential roles of secretory mucins versus membrane-associated mucins in the
      development of cardiac myxoma.

PMID- 15568158
TI  - Osteopontin expression in ductal adenocarcinomas and undifferentiated carcinomas
      of the pancreas.
AB  - Osteopontin (OPN) is a non-collagenous extracellular matrix protein with
      pleiotropic functions, including mediation of cell adhesion and migration.
      Recently, high OPN serum levels were found in pancreatic ductal adenocarcinomas
      (PDACs) in which OPN mRNA was identified in macrophages. We investigated OPN
      expression at the protein level in 15 PDACs and 10 undifferentiated pancreatic
      carcinomas (UCs), 4 of them with osteoclast-like giant cells (OCGCs), to find out
      whether the degree of OPN expression is related to tumor infiltration by
      macrophages and the adhesive capacity of tumor cells. With regard to its
      potential adhesive function, we compared OPN expression in PDACs and UCs with
      that of E-cadherin and beta-catenin, two well-known adhesive molecules. OPN
      positivity was observed in two-thirds of PDACs (10/15) and in 7 UCs (7/10),
      including all 4 UCs with OCGCs. Apart from tumor cells, OPN was expressed in
      macrophages and OCGCs. When we assessed the relationship between the number of
      OPN-positive macrophages and tumor cells, we did not find any statistically
      significant correlation. There was also no correlation, either positive or
      negative, between OPN expression and E-cadherin and beta-catenin expression. The
      results demonstrated that, in PDACs and UCs, OPN is expressed in both tumor
      associated macrophages and tumor cells. The biological significance of this dual
      expression pattern is not yet known. It is, however, unlikely that OPN has an
      adhesive function, since its expression pattern differs distinctly from that of E
      cadherin or beta-catenin.

PMID- 15568159
TI  - [Topical application of morphine gel in inflammatory mucosal and cutaneous
      lesions].
AB  - AIM: The aim of this study was to demonstrate a peripheral local opioid effect
      using case examples involving inflammatory mucosal and cutaneous lesions.
      METHODS: A 0.1% morphine gel, mixed in the hospital pharmacy, was applied several
      times daily to inflammatory mucosal lesions (oral, anogenital and in one patient
      to a skin ulcer). The effects and side effects were documented. RESULT: All
      patients experienced a significant reduction in pain with the use of topical
      morphine gel and no side effects were seen. CONCLUSION: Topical peripheral
      application of morphine gel is a simple, effective method that can be carried out
      by patients several times a day with few side effects.

PMID- 15568160
TI  - Intestinal obstruction after inguinal and femoral hernia repair: a study of
      33,275 operations during 1992-2000 in Sweden.
AB  - The risk of intra-abdominal intestinal obstruction after open or laparoscopic
      hernioplasty is, to our knowledge, not known. The transabdominal laparoscopic
      (TAPP) route brings a potential risk of abdominal adhesions, which may increase
      the risk of postoperative intestinal obstruction. The pre-peritoneal route
      laparoscopically, totally extraperitoneal laparoscopic hernioplasty (TEP), should
      not increase this risk since the abdominal cavity is not entered. The Swedish
      Hernia Register, with 33,275 patients operated on for single primary unilateral
      groin hernia during the period 1992-2000, was linked to the Swedish Inpatient
      register and the Swedish Death register for the period 1987-2000. The risk of
      postoperative intestinal obstruction was low, 1.02 per 1,000 personyears. The
      highest adjusted relative risks (RR) were found in patients with previous
      admissions for abdominal inflammations or operations. The risk increased with the
      number of admissions. After an acute operation, and in patients older than 60
      years, there was also a significantly increased risk. The RR was 2.79 (95% CI
      1.01-7.42) after TAPP and 0.57 (95% CI 0.07-4.33) following TEP compared to
      patients operated on by the Lichtenstein method. None of the patients undergoing
      open hernia operations had a significantly increased risk. TAPP increased the
      risk of postoperative intestinal obstruction, but other risk factors, especially
      previous abdominal surgery or inflammation, have greater influence.

PMID- 15568161
TI  - Adequacy of plain radiography in the diagnosis of cervical spine injuries.
AB  - Our hypotheses were (1) that plain radiography of the cervical spine in the
      evaluation of low risk patients with minor blunt trauma is accurate and (2) that
      computed tomography (CT) of the cervical spine in the evaluation of low risk
      patients is unnecessary. This study evaluates those hypotheses. We prospectively
      recorded findings of all patients with blunt trauma who underwent imaging over a
      period of 70 days. Injury status was determined by review of all radiographic
      studies obtained on each patient. Chart reviews were performed to determine
      mechanism of injury and neurological status. Patients were divided into three
      groups: very low risk, low risk, and high risk. Study end point was fracture. The
      study included 219 patients. The very low risk group had 107 patients, none of
      whom had fractures found on CT (projected specificity of plain radiography:
      100%). The low risk group contained 78 patients who had no fractures seen on
      plain radiography or CT (specificity of plain radiography and CT: 100%). The high
      risk group consisted of 34 patients; 15 had fractures demonstrated on CT. Plain
      radiography missed one fracture out of 15. In low risk patients, plain
      radiography is an efficient diagnostic exam with a specificity of 100%. In high
      risk patients, plain radiography is a good adjunctive screening exam in
      conjunction with CT scan, with a sensitivity of 93.3% and specificity of 95%.

PMID- 15568163
TI  - [LVI Annual Meeting of the Spanish Society of Neurology. Barcelona, Spain, 24-27
      November 2004. Abstracts].

PMID- 15568166
TI  - [Message from the outgoing editors].

PMID- 15568167
TI  - [Sleep disorders in multiple sclerosis].
AB  - INTRODUCTION: To determine the frequency of sleep disorders in multiple sclerosis
      (MS) patients and their relation with other manifestations of the disease.
      METHODS: Selected patients had clinically definite MS (relapsing-remitting and
      secondary progressive forms) and duration of the disease over two years. They
      were serially evaluated at the unit of demyelinating diseases of a third level
      hospital. The following scales were applied: the Pittsburgh Sleep Quality Index,
      the Hamilton Depression Rating Scale, EDSS, ISS and ESS. Statistical analysis by
      means of non parametric test and logistic regression was carried out. RESULTS:
      One hundred patients were included (72% women and 28% males). Mean age was 39
      years. Eighty eight were relapsing-remitting forms and the rest secondary
      progressive forms. Mean EDSS was: 2.5. Mean duration of evolution: 11.2 years.
      The prevalence of sleep disorders was 36%. Age, sex, evolutionary form, degree of
      disability and chronic fatigue did not relate with the sleep disorders in these
      patients. In the multivariant analysis by means of logistic regression, we found
      that every point more in Hamilton's scale multiplies the probability of
      presenting sleep disorders by 1.2. CONCLUSIONS: Depression is the only variable
      that independently relates, with the presence of sleep disorders in MS patients.

PMID- 15568168
TI  - [Influence of levodopa on cognition of idiopathic Parkinson's disease].
AB  - INTRODUCTION: Idiopathic Parkinson's disease induces alterations both motor and
      cognitive. Levodopa, the treatment of choice, offers initial improvement, but
      causes long term important complications. It is ignored if it provokes or not a
      similar situation in cognitive function. METHOD: Two groups of idiopathic
      parkinsonian patients were studied. One of them was using levodopa as a regular
      treatment, the other had de novo patients. A group of healthy controls was also
      studied. The levodopa group was evaluated when levodopa plasma concentration was
      maximum and when it was minimum. A cognitive battery was used in order to assess
      the cognitive status of all subjects. RESULTS: Significant differences between
      the two groups of patients and the healthy controls were found when the treated
      group had a maximum plasmatic concentration of levodopa. There were also
      significant differences when they had a minimum concentration in comparison with
      the healthy controls. The performances of the patients taking levodopa varied
      between both conditions. CONCLUSIONS: Parkinson's disease provokes a wide variety
      of cognitive alterations, therefore basal ganglia can be related to a more
      general function as learning and storing cognitive and motor programs. Levodopa
      influences in a different way different cognitive functions differently and its
      influence varies between highest and lowest plasmatic concentrations periods.
      These results allow us to draw important conclusions about the cognitive
      alterations caused by the natural course of Parkinson's disease, the introduction
      of treatment with levodopa and the relationship between basal ganglia and human
      cognition.

PMID- 15568169
TI  - [Clinical utility of deep brain stimulation in an advanced Parkinson's disease].
AB  - INTRODUCTION: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus
      (STN) or globus pallidus internus (GPi) have demonstrated efficacy in advanced
      Parkinson's disease (PD). We aimed to assess the clinical utility of these
      procedures in terms of the quality of life, and to determine the pre and
      postsurgical characteristics related to the outcome. METHOD: A prospective study
      was conducted on a cohort of 20 patients with advanced PD who underwent bilateral
      DBS: 14 in STN and 6 in GPi. They were assessed according to the CAPSIT-PD
      protocol before and after surgery, with a mean follow-up of 9 and 11 months,
      respectively. The main outcome variables were change in the UPDRS III score in
      off efficacy and the PDQ-39 quality of life questionnaire score (clinical
      utility). RESULTS: The STN group improved their UPDRS III in off by a mean of 35%
      (p = 0.001) and their PDQ-39 by 21% (p = 0.026). The GPi group improved their
      UPDRS III in off by 21% (p = 0.028) and their PDQ-39 by 37% (p = 0.116). The
      presurgical levodopa-equivalent dose was a positive predictor of the efficacy and
      clinical utility of STN DBS and a negative predictor of the efficacy of GPi DBS.
      In both groups, the clinical utility was determined by improvement in functional
      disability in off scales. CONCLUSIONS: Bilateral DBS demonstrated middle-term
      efficacy and clinical utility in the treatment of advanced PD. The presurgical
      levodopa-equivalent dose was a predictor of the efficacy and clinical utility of
      DBS.

PMID- 15568170
TI  - [Multiple sclerosis in the XXI century].
AB  - Multiple sclerosis is possibly one of the diseases that bets illustrates progress
      in Neurology over the last years. The present article reviews the most
      significant changes that have occurred in almost all the aspects of this disease.
      These changes have produced a profound modification in the understanding of
      multiple sclerosis and have encouraged the development of innovative therapies.

PMID- 15568171
TI  - [Prehistory of Parkinson's disease].
AB  - Parkinson's disease (PD) was described according to conventional history in 1817.
      However, PD has been known and partially described since the Biblical times.
      There are descriptions of parkinsonian symptoms in Indian and Egyptian texts.
      Galen also paid attention to rest tremor. Parkinsonian symptoms were also
      mentioned by several authors since the XVII century including Tulp, Silvio de la
      Boe, Johannes Baptiste Sagar, Gaubius, Boissier de Sauvages, Hunter and Chomel.
      Certainly James Parkinson deserves to be recalled after his text devoted to
      shaking palsy, but he also recognized he contribution of previous authors.

PMID- 15568172
TI  - [Current controversies in pathophysiology of cervical spondylotic myelopathy].
AB  - Cervical spondylotic myelopathy is the most severe consequence of degenerative
      disease of cervical spine. In this article we perform a bibliographic review,
      addressing current controversies in its pathophysiology. Present work lines of
      most groups dedicated to the study of this condition are focused on improving
      surgical techniques designed for the treatment of this disease.
      Pathophysiological studies are scarce, and most of our pathophysiological
      knowledge of cervical spondylotic myelopathy is based in works done in 60s and
      70s. Literature of the last decade lacks neurochemichal studies parallel to those
      existing for acute spinal injury. In the same way, only three prospective
      clinical trials comparing conservative and surgical treatment have been done, and
      none of them has demonstrated clear superiority of surgery. Given the high
      prevalence of this disease, the need for deep knowledge of its pathophysiologic,
      neurochemichal and molecular basis, and the optimization of surgical treatment is
      justified. This probably implies the need for prospective randomized trials to
      determine which patients are going to benefit from surgery.

PMID- 15568173
TI  - [Balint syndrome due to hypoxic encephalopathy after cardiorespiratory arrest].

PMID- 15568174
TI  - [Acute confusional state secondary to transient headache and neurological
      deficits with cerebrospinal fluid lymphocytosis].
AB  - Pseudomigraine with pleocytosis (now referred to as syndrome of transient
      headache and neurological deficits with cerebrospinal fluid lymphocytosis, IHS
      ICHD-II code 7.8) is only infrequently accompanied by a confusional state and no
      cases have been described so far in association with severe agitation. We report
      on a patient who suffered from two episodes of headache with transient focal
      neurological deficits that were consistent with pseudomigraine with pleocytosis
      but that were followed by an intense confusional, agitated state that required
      admission in the intensive care unit. This possibility should be included in the
      differential diagnosis of confusional, agitated states.

PMID- 15568175
TI  - [Intracranial artifact un magnetic resonance caused by embolization of
      microscopic metallic fragment].
AB  - Magnetic resonance imaging (MRI) artifacts have been described in many articles
      published in the literature. We present the case of a 72 year old man who was
      admitted due to left inferior limb weakness. MRI imaging demonstrated an acute
      right infarction of the right posterior cerebral artery. In the right frontal
      lobe a metallic artifact was demonstrated as well. The artifact showed a central
      signal void and it was surrounded by a high signal intensity rim. His aortic
      valve had been replaced 12 years earlier. This indicates that the artifact is in
      fact due to a small metallic fragment embolization during cardiac surgery.

PMID- 15568176
TI  - [Anticoagulant treatment in hemorrhagic brains infarts due to large sinus venous
      thrombosis].
AB  - Cerebral venous and sinus thrombosis is an infrequent condition which presents
      with a wide spectrum of signs and a variable mode of onset. Sinus thrombosis may
      cause isolated intracranial hypertension but also may cause cerebral venous
      infarcts, which are frequently hemorrhagic. Treatment with antithrombotic agents
      is controversial because there is only one randomised controlled trial with
      unfractionated heparin. We report a 46- years-old man complaining of progressive
      headache, paraparesis and dysphasia. After admission, his neurological status
      worsened and he developed tetraparesis, depressed level of consciousness and
      seizures. A cranial computarized tomography (CT) scan showed multiple
      hyperdensities suggestive of hemorrhagic infarcts. Magnetic resonance imaging
      (MRI) study confirmed extensive cerebral venous thrombosis. Unfractionated
      heparin was administered for two weeks followed by acenocumarol. Within a few
      days his neurological status improved, and five weeks after admission the patient
      only hadd slight neurological deficit. After 11 years of follow-up, he has had a
      complete recovery. The G20210A mutation in the prothrombin gene was detected as a
      likely risk factor for venous thrombosis. Therapeutical and diagnosis aspects are
      discussed. We review the previous literature on the topic.

PMID- 15568177
TI  - [Acute transverse myelitis as part of the catastrophic antiphospholipid syndrome
      in a systemic lupus erythematosus patient].

PMID- 15568178
TI  - [Semiology of the nervous system. From symptoms to diagnosis].

PMID- 15568180
TI  - Azido sialic acids can modulate cell-surface interactions.

PMID- 15568183
TI  - Concordance correlation in the measurements of time to event.
AB  - The concordance correlation coefficient (CCC), a measure of concordance in
      ratings from multiple raters, was used to study inter-rater agreement in
      measurements of time to event, generally not observed with perfect consistency
      among raters. As a function of the first two moments of rating measures, the CCC
      can be estimated with data subject to censoring, using a likelihood-based
      estimation method applied under the assumptions of random censoring and
      parametric distribution models for the ratings of time to event. A simulation
      study was conducted for small sample performance under various censoring
      proportions. The use of the CCC with censored data is illustrated with an example
      taken from a data set containing data on time to an event with two raters per
      subject.

PMID- 15568184
TI  - Structural characterization of methionine and leucine enkephalins by
      hydrogen/deuterium exchange and electrospray ionization tandem mass spectrometry.
AB  - Conformational changes in two endogenous opioid active pentapeptides methionine
      enkephalin (Met-enk) and leucine enkephalin (Leu-enk) induced by trifluoroethanol
      (TFE) were identified using hydrogen/deuterium exchange (HDX), coupled with
      electrospray ionization (ESI) mass spectrometry. The exchange features in
      individual amino acid residues were characterized by acquiring tandem mass
      spectra of the deuterated peptides. The exact identity of the labile hydrogens
      involved in HDX reveals that the monomer forms of both peptides adopt an unfolded
      conformation in aqueous solvent, but prefer the 5-->2 beta-turn secondary
      structure under the membrane-mimetic environment. The ESI mass spectra of Met-enk
      and Leu-enk also reveal that the dimer structure of these peptides coexists with
      the monomer conformation. The extent of the dimer structure is dependent on the
      peptide concentration and nature of the solvent. The non-polar solvents
      facilitate the dimer formation.

PMID- 15568185
TI  - Identifying target populations for screening or not screening using logic
      regression.
AB  - Colorectal cancer remains a significant public health concern despite the fact
      that effective screening procedures exist and that the disease is treatable when
      detected at early stages. Numerous risk factors for colon cancer have been
      identified, but none are very predictive alone. We sought to determine whether
      there are certain combinations of risk factors that distinguish well between
      cases and controls, and that could be used to identify subjects at particularly
      high or low risk of the disease to target screening. Using data from the Seattle
      site of the Colorectal Cancer Family Registry, we fit logic regression models to
      combine risk factor information. Logic regression is a methodology that
      identifies subsets of the population, described by Boolean combinations of binary
      coded risk factors. This method is well suited to situations in which
      interactions between many variables result in differences in disease risk. We
      found that neither the logic regression models nor stepwise logistic regression
      models fit for comparison resulted in criteria that could be used to direct
      subjects to screening. However, we believe that our novel statistical approach
      could be useful in settings where risk factors do discriminate between cases and
      controls, and illustrate this with a simulated data set.

PMID- 15568186
TI  - Summarizing data through a piecewise linear growth curve model.
AB  - Most of the research in clinical trials is based on longitudinal designs, which
      involve repeated measurements of a variable of interest. Such designs are very
      powerful, both statistically and scientifically. Recent advances in statistical
      theory and software development incorporate the covariance structures such as
      unstructured, compound symmetry, auto-regressive and random effects, etc., for
      analysing longitudinal data. Hathaway et al. propose a technique for summarizing
      longitudinal data using linear growth curve model and establish that the number
      of summary statistics is fixed as four irrespective of the length of study. In
      this paper, we develop a procedure for analysing the longitudinal data through a
      piecewise linear growth curve model on the lines of Hathaway et al. Under
      different covariance structures, the linear model is fitted for Leprosy data and
      the residual sum of squares computed. Goodness of fit has also been considered
      for various models. In order to prove that the proposed method is robust and
      better than the others in terms of goodness of fit, simulation studies are
      carried out and the results presented.

PMID- 15568187
TI  - Tests for treatment group differences in the hazards for survival, before and
      after the occurrence of an intermediate event.
AB  - In many settings, one would expect that the hazard for a terminal event would
      change with the occurrence of an intermediate event. For example, in an AIDS
      clinical trial, it is of interest to assess whether there is a difference between
      treatments in the hazards for death prior to drop in Karnofsky performance score
      and in the hazards subsequent to the drop in Karnofsky score. Tests for the
      effect of treatment on these hazard functions, separately or jointly, are useful
      in conjunction with tests of overall survival. We consider four Cox regression
      models for the hazard function, constructed by allowing for various combinations
      of time-dependent stratification and time-dependent covariates, both of which are
      based on the occurrence of the intermediate event. Assuming a Markov transition
      model from the intermediate to the terminal event, partial likelihoods can be
      used for inference, enabling the use of standard statistical software for
      computation. We develop analytic approximations for the power of the derived
      score tests for treatment differences in the hazard functions and evaluate them
      through simulations. We apply our results to AIDS Clinical Trials Group (ACTG)
      protocol 021.

PMID- 15568188
TI  - Sample size calculations for comparative clinical trials with over-dispersed
      Poisson process data.
AB  - This paper develops a new formula for sample size calculations for comparative
      clinical trials with Poisson or over-dispersed Poisson process data. The criteria
      for sample size calculations is developed on the basis of asymptotic
      approximations for a two-sample non-parametric test to compare the empirical
      event rate function between treatment groups. This formula can accommodate time
      heterogeneity, inter-patient heterogeneity in event rate, and also, time-varying
      treatment effects. An application of the formula to a trial for chronic
      granulomatous disease is provided.

PMID- 15568189
TI  - Estimating the growth rates of primary lung tumours from samples with missing
      measurements.
AB  - A method to estimate the population variability in tumour growth rate using
      incomplete data was developed. We assume exponential growth and lognormal
      distribution for the parameter of the growth curve. Estimates of growth rate
      obtained based on the cases with two measurements, one of which is obtained
      retrospectively, are biased towards lower growth rate. For the data sets where
      two measurements are available for some tumours and only one measurement for
      others (which means that no tumour was seen in retrospect for those cases),
      several approaches were developed that can eliminate or substantially reduce the
      bias. The relative error of the best estimates, as assessed by simulation, rarely
      exceeds 20 per cent. We found that the results of application of our estimation
      procedures to chest X-ray screening data agree well with the expectations.

PMID- 15568190
TI  - A method for meta-analysis of molecular association studies.
AB  - Although population-based molecular association studies are becoming increasingly
      popular, methodology for the meta-analysis of these studies has been neglected,
      particularly with regard to two issues: testing Hardy-Weinberg equilibrium (HWE),
      and pooling results in a manner that reflects a biological model of gene effect.
      We propose a process for pooling results from population-based molecular
      association studies which consists of the following steps: (1) checking HWE using
      chi-square goodness of fit; we suggest performing sensitivity analysis with and
      without studies that are in HWE. (2) Heterogeneity is then checked, and if
      present, possible causes are explored. (3) If no heterogeneity is present,
      regression analysis is used to pool data and to determine the gene effect. (4) If
      there is a significant gene effect, pairwise group differences are analysed and
      these data are allowed to 'dictate' the best genetic model. (5) Data may then be
      pooled using this model. This method is easily performed using standard software,
      and has the advantage of not assuming an a priori genetic model.

PMID- 15568191
TI  - The application of enhanced parallel gatekeeping strategies.
AB  - The parallel gatekeeping strategy proposed by Dmitrienko et al. (Statist. Med.
      2003; 22:2387-2400) provides a flexible framework for the pursuit of strong
      control on study wise type I error rate. This paper further explores the
      application of the weighted Simes parallel gatekeeping procedure recommended by
      Dmitrienko et al. and proposes some modifications to it to better incorporate the
      interrelationships of different hypotheses in actual clinical trials and to
      achieve better power performance. We first propose a simple method to
      quantitatively control the impact of secondary tests on the testing of primary
      hypotheses. We then introduce a matched gatekeeping procedure to exemplify how to
      address special relationships between individual primary and secondary tests
      following the parallel gatekeeping framework. Our simulation study demonstrates
      that the enhanced gatekeeping procedures generally result in more powerful tests
      than the parallel gatekeeping procedure in Dmitrienko et al. whenever applicable.

PMID- 15568192
TI  - Bayesian inference for recurrent events data using time-dependent frailty.
AB  - In medical studies, we commonly encounter multiple events data such as recurrent
      infection or attack times in patients suffering from a given disease. A number of
      statistical procedures for the analysis of such data use the Cox proportional
      hazards model, modified to include a random effect term called frailty which
      summarizes the dependence of recurrent times within a subject. These unobserved
      random frailty effects capture subject effects that are not explained by the
      known covariates. They are typically modelled constant over time and are assumed
      to be independently and identically distributed across subjects. However, in some
      situations, the subject-specific random frailty may change over time in the same
      manner as time-dependent covariate effects. This paper presents a time-dependent
      frailty model for recurrent failure time data in the Bayesian context and
      estimates it using a Markov chain Monte Carlo method. Our approach is illustrated
      by a data set relating to patients with chronic granulomatous disease and it is
      compared to the constant frailty model using the deviance information criterion.

PMID- 15568193
TI  - Concomitant information in bioassay and semi-parametric estimation.
AB  - This paper presents a flexible modern approach to handling concomitant
      information for estimating the relative potency parameter in quantitative
      bioassays. This is accomplished in a semi-parametric framework where the
      concomitant variable is included non-parametrically. Estimation is then performed
      using smoothing splines where the point and interval estimators of the relative
      potency parameter exhibits desirable asymptotic properties.

PMID- 15568194
TI  - Funnel plots for comparing institutional performance.
AB  - 'Funnel plots' are recommended as a graphical aid for institutional comparisons,
      in which an estimate of an underlying quantity is plotted against an
      interpretable measure of its precision. 'Control limits' form a funnel around the
      target outcome, in a close analogy to standard Shewhart control charts. Examples
      are given for comparing proportions and changes in rates, assessing association
      between outcome and volume of cases, and dealing with over-dispersion due to
      unmeasured risk factors. We conclude that funnel plots are flexible, attractively
      simple, and avoid spurious ranking of institutions into 'league tables'.

PMID- 15568195
TI  - The impact of diagnostic error on testing genetic association in case-control
      studies.
AB  - In case-control studies, subjects in the case group may be recruited from
      suspected patients who are diagnosed positively with disease. While many
      statistical methods have been developed for measurement error or
      misclassification of exposure variables in epidemiological studies, no studies
      have been reported on the effect of errors in diagnosing disease on testing
      genetic association in case-control studies. We study the impact of using the
      original Cochran-Armitage trend test assuming no diagnostic error when, in fact,
      cases and controls may be clinically diagnosed by an imperfect gold standard or a
      reference test. The type I error, sample size and asymptotic power of trend tests
      are examined under a family of genetic models in the presence of diagnostic
      error. The empirical powers of the trend tests are also compared by simulation
      studies under various genetic models.

PMID- 15568196
TI  - Small-molecule screening and profiling by using automated microscopy.
AB  - Automated fluorescence microscopy provides a powerful tool for analyzing the
      physiological state of single cells with high throughput and high information
      content. Here I discuss two types of experiments in which this technology was
      used to discover and characterize bioactive small molecules. In phenotypic
      screening experiments, the goal is to find "hits" with specific effects on cells
      by screening large libraries of small molecules. An example is screening for
      small molecules that perturb mitosis by novel mechanisms. In cytological
      profiling experiments, the goal is to characterize the bioactivity of a limited
      number of small molecules in considerable depth, and thus understand their
      mechanism and toxicities at the cellular level. I discuss an example in which 100
      small molecules with known bioactivity were profiled by using multiple
      fluorescent probes, and clustered into mechanistic classes by automated
      statistical analysis.

PMID- 15568197
TI  - High-content screening and profiling of drug activity in an automated centrosome
      duplication assay.
AB  - Maintenance of centrosome number is essential for cell-cycle progression and
      genomic stability, but investigation of this regulation has been limited by assay
      difficulty. We present a fully automated image-based centrosome-duplication assay
      that is accurate and robust enough for both careful cell-biology studies and high
      throughput screening, and employ this assay in a series of chemical-genetic
      studies. We observe that a simple cytometric profiling strategy, which is based
      on organelle size, groups compounds with similar mechanisms of action; this
      suggests a simple strategy for excluding compounds that undesirably target such
      activities as protein synthesis and microtubule dynamics. Screening a library of
      compounds of known activity, we found unexpected effects on centrosome
      duplication by a number of drugs, most notably isoform-specific protein kinase C
      inhibitors and retinoic acid receptor agonists. From a 16 320-member library of
      uncharacterized small molecules, we identified five potent centrosome-duplication
      inhibitors that do not target microtubule dynamics or protein synthesis. The
      analysis methodology reported here is directly relevant to studies of centrosome
      regulation in a variety of systems and is adaptable to a wide range of other
      biological problems.

PMID- 15568198
TI  - Aminoglycoside-hybrid ligands targeting the ribosomal decoding site.

PMID- 15568199
TI  - The effects of rational and experiential information processing of expert
      testimony in death penalty cases.
AB  - Past research examining the effects of actuarial and clinical expert testimony on
      defendants' dangerousness in Texas death penalty sentencing has found that jurors
      are more influenced by less scientific pure clinical expert testimony and less
      influenced by more scientific actuarial expert testimony (Krauss & Lee, 2003;
      Krauss & Sales, 2001). By applying cognitive-experiential self-theory (CEST) to
      juror decision-making, the present study was undertaken in an attempt to offer a
      theoretical rationale for these findings. Based on past CEST research, 163 mock
      jurors were either directed into a rational mode or experiential mode of
      processing. Consistent with CEST and inconsistent with previous research using
      the same stimulus materials, results demonstrate that jurors in a rational mode
      of processing more heavily weighted actuarial expert testimony in their
      dangerousness assessments, while those jurors in the experiential condition were
      more influenced by clinical expert testimony. The policy implications of these
      findings are discussed.

PMID- 15568200
TI  - MMPI inmate profiles: suicide completers, suicide attempters, and non-suicidal
      controls.
AB  - Results from the Minnesota Multiphasic Personality Inventory (MMPI) were compared
      for three groups of male inmates in federal penitentiaries: 47 suicide
      completers, 43 suicide attempters and, 123 non-suicidal controls. Analyses show
      that the groups differed on all 10 clinical scales and on at least 8 after
      Bonferroni correction. Attempters obtained the highest scores on 4 of 8 scales;
      they also posted the highest scores on 3 others, but differences were significant
      only against non-suicidal controls. Completers posted the highest score on only
      one scale (Mf), but the difference was significant only against non-suicidal
      controls. All told, completers proved more similar to non-suicidal controls than
      to attempters. Regarding profiles, completers are more strongly correlated with
      non-suicidal controls (r=0.95) than with attempters (r=0.86); non-suicidal
      controls are less strongly correlated with attempters (r=0.88). The fact that
      attempters seem more pathological than the others can mislead clinicians
      screening for suicide risk.

PMID- 15568201
TI  - Simple fitting of subject-specific curves for longitudinal data.
AB  - We present a simple semiparametric model for fitting subject-specific curves for
      longitudinal data. Individual curves are modelled as penalized splines with
      random coefficients. This model has a mixed model representation, and it is
      easily implemented in standard statistical software. We conduct an analysis of
      the long-term effect of radiation therapy on the height of children suffering
      from acute lymphoblastic leukaemia using penalized splines in the framework of
      semiparametric mixed effects models. The analysis revealed significant
      differences between therapies and showed that the growth rate of girls in the
      study cannot be fully explained by the group-average curve and that individual
      curves are necessary to reflect the individual response to treatment. We also
      show how to implement these models in S-PLUS and R in the appendix.

PMID- 15568202
TI  - A neuropsychiatric developmental model of serial homicidal behavior.
AB  - Serial sexual homicide has been the object of intensive study from forensic
      psychiatric, criminological, developmental, and sociological perspectives. In
      contradistinction to these approaches, neuropsychiatric concepts and methods have
      received relatively little attention in this area. In this article we adopt a
      neuropsychiatric developmental perspective and undertake a review of the
      psychiatric literature on violence and autism spectrum disorders. Our analysis of
      this literature suggests the presence of an association between autism spectrum
      psychopathology and serial homicidal behavior. Recommendations for further
      research to help clarify the nature of this association are briefly discussed.

PMID- 15568203
TI  - Visual experience can substantially alter critical flicker fusion thresholds.
AB  - Studies of psychopharmacology often use the test of the critical flicker fusion
      (CFF) threshold as a measure of total information processing. It is true that
      studies of practice effects have shown that CFF thresholds are remarkably stable
      within and across multiple days of testing. This study confirms that subjects who
      undergo CFF testing on sequential days have stable thresholds, but also
      demonstrates that in subjects who conducted 1 h of motion training per day for 9
      days the CFF thresholds increased by an average of 30%. The results show that the
      perceptual experience of subjects can dramatically alter the CFF thresholds and
      should be an important consideration in the control of studies employing the CFF
      as a measure.

PMID- 15568204
TI  - Measuring HIV vaccine efficacy.
AB  - Some HIV vaccine candidates have a potential VE I (vaccine efficacy for
      infectiousness) type effect, which tends to reduce the viral load and may reduce
      infectiousness of an infected individual. In general, the efficacy of this kind
      of vaccine is very difficult to assess because it requires information on
      contacts of vaccinated infected individuals, and current methods to estimate VE I
      rely on the time elapsed between infections of an individual and his/her sexual
      partner, thus making infection of the sexual partner necessary to assess the
      efficacy. To avoid behavioural changes that may affect the estimates, HIV status
      is kept undisclosed to participants, which raises many ethical questions. Here we
      present a method that allows immediate notification of HIV status to both members
      of a couple, reducing the risk of infection when one of them has not been
      infected and allowing immediate medical treatment. The method allows for
      estimation of any VE I and VE S (vaccine efficacy for susceptibility) effect, and
      it is robust to the most common situations found in these type of studies,
      namely: differential risk of participants, staggered enrollment and small sample
      sizes.

PMID- 15568205
TI  - Treatment of acute mania--from clinical trials to recommendations for clinical
      practice.
AB  - No consensus has been reached with regard to the treatment of bouts of acute
      mania in various parts of the world. Controlled clinical trials have, at last,
      provided irrefutable evidence of the activity of lithium, which has long been
      used alone, as well as that of divalproate or its derivatives and, to a lesser
      extent, carbamazepine. The new antipsychotic agents have more recently
      established their efficacy, especially olanzapine, risperidone and aripiprazole.
      It is paradoxical to note that, in Europe, haloperidol is still the reference
      substance used in clinical trials despite the fact that it is not officially
      indicated in the treatment of mania. In the USA, lithium, divalproate or
      antipsychotics can be prescribed as first-line treatment. In Europe, lithium
      remains the first-line medication, whereas divalproate and atypical antipsychotic
      agents are used only as second-line therapy. The conventional antipsychotic
      agents (such as haloperidol, loxapine or zuclopenthixol) which should no longer
      be prescribed during manic episodes given the potential risks and side effects
      associated with these substances (extrapyramidal side effects, depressogenic
      effect, malignant syndrome) are still prescribed extensively in Europe. Although
      both types of medication (antipsychotics, normothymic agents and/or
      anticonvulsants) have proved to be clinically effective in the management of
      mania by reducing the mania scores overall, the same does not apply, however, to
      all symptoms of mania. Factorial approaches to mania have all shown that since
      there are several clinical forms of mania, several lines of manic symptoms can be
      identified. Antipsychotic and normothymic agents and/or anticonvulsants do not
      appear to have the same effects on each of these identifiable clusters of
      symptoms, mainly psychotic features. We believe that it is vitally important for
      future clinical trials of mania treatment to focus on the treatment effect by
      adopting a factorial approach to the episode with an appropriate methodological
      structure provided to this end. These questions highlight the uncertainty
      shrouding the very structure of manic episodes, namely that these are
      predominantly of a thymic or psychotic nature. The Europeans undoubtedly consider
      mania to be more of a thymic episode and prefer lithium as the first-line
      treatment, whereas the Americans believe that psychotic symptoms dominate and
      widely prescribe antipsychotic agents. However, from the standpoint of clinical
      trials currently available, even though antipsychotic agents are certainly
      effective in reducing the scores on the mania scales, can they be considered
      purely as antimania treatments?

PMID- 15568206
TI  - Effects of caffeine in non-withdrawn volunteers.
AB  - RATIONALE: Evidence for the behavioural effects of caffeine is prevalent in the
      literature. It is associated with increased subjective alertness, improved
      reaction time and enhanced encoding of new information. However, there is an on
      going debate as to whether such changes are in fact improvements or merely a
      reversal of the negative effects of caffeine withdrawal. Using participants who
      had consumed their normal daily quota of caffeine this study alleviated this
      potential confound as all participants were not withdrawn at the time of testing.
      OBJECTIVES: To determine whether caffeine influenced the mood and performance of
      non-withdrawn volunteers. METHODS: Sixty eight volunteers, all of whom were
      regular caffeine consumers, consumed their normal amount of caffeine over the
      course of the day. Baseline measures of mood and performance were then carried
      out followed by double-blind administration of caffeine (2 mg/kg) or placebo. The
      test battery was repeated again 30 min after ingestion of the drink. RESULTS: Our
      findings showed improvements comparable to previous research. Mood was improved
      and performance on a number of cognitive measures was improved. The findings are
      discussed in relation to both noradrenergic and cholinergic neurotransmitter
      systems. CONCLUSIONS: This study provided evidence against the argument that
      behavioural changes due to caffeine are merely the reversal of negative
      withdrawal effects.

PMID- 15568207
TI  - Statistical consideration of the strategy for demonstrating clinical evidence of
      effectiveness--one larger vs two smaller pivotal studies.
AB  - As a regulatory strategy, it is nowadays not uncommon to conduct one confirmatory
      pivotal clinical trial, instead of two, to demonstrate efficacy and safety in
      drug development. This paper is intended to investigate the statistical
      foundation of such an approach. The one-study approach is compared with the
      conventional two-study approach in terms of power, type-I error, and fundamental
      statistical assumptions. Necessary requirements for a single-study model is
      provided in order to maintain equivalent evidence as that from a two-study model.
      In general, one-study model is valid only under a 'one population' assumption. In
      addition, higher data quality and more convincing and robust results need to be
      demonstrated in such cases. However, when 'one-population' assumption is valid
      and appropriate methods are selected, a one-study model can have a better power
      using the same sample size. The paper also investigates statistical assumptions
      and methods for making an overall inference when a two-study model has been used.
      The methods for integrated analysis are evaluated. It is important for
      statisticians to select correct pooling strategy based on the project objective
      and statistical hypothesis.

PMID- 15568208
TI  - Prediction of ordinal outcomes when the association between predictors and
      outcome differs between outcome levels.
AB  - There are a number of regression models which are widely used to predict ordinal
      outcomes. The commonly used models assume that all predictor variables have a
      similar effect at all levels of the outcome variable. If this is not the case,
      for example if some variables predict susceptibility to a disease and others
      predict the severity of the disease, then a more complex model is required. One
      possibility is the multinomial logistic regression model, which assumes that the
      predictor variables have different effects at all levels of the outcome variable.
      An alternative is to use the stereotype family of regression models. A one
      dimensional stereotype model makes the assumption that the effect of each
      predictor is the same at all outcome levels. However, it is possible to fit
      stereotype models with more than one dimension, up to a maximum of min(k-1, p)
      where k is the number of outcome categories and p is the number of predictor
      variables. A stereotype model of this maximum dimension is equivalent to a
      multinomial logistic regression model, in that it will produce the same predicted
      values and log-likelihood. If there are sufficient outcome levels and/or
      predictor variables, there may be a number of stereotype models of differing
      dimension. The method is illustrated with an example of prediction of damage to
      joints in rheumatoid arthritis.

PMID- 15568209
TI  - Methods for assessing the accuracy of PCR-based tests: comparisons and
      extensions.
AB  - Polymerase chain reaction (PCR) based tests are commonly used to diagnose various
      infections. Such tests are assumed to be highly 'sensitive', however, no
      consensus definition of, or method for estimating, sensitivity exists. Hughes and
      Totten proposed that sensitivity be defined as a function of the number of target
      DNA molecules in the sample with specificity corresponding to the case where
      there is no target DNA molecule present. They then developed parametric, non
      parametric and semi-parametric models for estimating the sensitivity curve. In
      this paper a general model is proposed that yields their three models as special
      cases when specificity is assumed to be 1.0. We also extend the general model to
      incorporate covariates. Simulation studies are used to compare the different
      estimators. The methods are applied to data from a PCR-based test for Mycoplasma
      genitalium.

PMID- 15568210
TI  - Semi-parametric modelling for costs of health care technologies.
AB  - Cost data that arise in the evaluation of health care technologies usually
      exhibit highly skew, heavy-tailed and, possibly, multi-modal distributions.
      Distribution-free methods for analysing these data, such as the bootstrap, or
      those based on the asymptotic normality of sample means, may often lead to
      inefficient or misleading inferences. On the other hand, parametric models that
      fit the data (or a transformation of the data) equally well can produce very
      different answers. We consider a Bayesian approach, and model cost data with a
      distribution composed of a piecewise constant density up to an unknown endpoint,
      and a generalized Pareto distribution for the remaining tail.

PMID- 15568211
TI  - Lawrence Z Freedman.

PMID- 15568212
TI  - Copper oxide superconductors: sharp-mode coupling in high-Tc superconductors.
AB  - In conventional superconductivity, sharp phonon modes (oscillations in the
      crystal lattice) are exchanged between electrons within a Cooper pair, enabling
      superconductivity. A critical question in the study of copper oxides with high
      critical transition temperature (Tc) is whether such sharp modes (which may be
      more general, including, for example, magnetic oscillations) also play a critical
      role in the pairing and hence the superconductivity. Hwang et al. report evidence
      that sharp modes (either phononic or magnetic in origin) are not important for
      superconductivity in these materials, but we show here that their conclusions are
      undermined by the insensitivity of their experiment to a crucial physical effect.

PMID- 15568213
TI  - The challenges of vasoformative tumors of the liver in children.

PMID- 15568214
TI  - Maternal smoking, intrauterine growth restriction, and placental apoptosis.
AB  - Pregnant women who smoke are at greater risk of delivering a growth-restricted
      infant than nonsmoking mothers. We wanted to see if apoptosis could be involved
      in the mechanisms behind smoke-induced growth restriction, and our aim was to
      compare apoptosis in the placenta of smoking mothers giving birth to growth
      restricted infants and nonsmoking mothers with infants of appropriate weight. The
      project was conducted at the Magee--Womens Hospital and Magee--Womens Research
      Institute, University of Pittsburgh, PA. Histological sections from 20 placentas
      were selected from smoking mothers who had given birth to small-for-gestational
      age infants (birth weight < or = 2 SD). The controls were gestational-age matched
      nonsmoking mothers with infants having appropriate-for-gestational-age weight.
      The TUNEL method was used to demonstrate DNA fragmentation in nuclei, and a
      monoclonal antibody M30, specific for a neo-epitope on cytokeratin 18, was used
      to identify apoptotic epithelial cells. The positive nuclei (TUNEL) and positive
      cells (M30-positive cytoplasm) were counted blindly both in villous tissue and in
      decidual/basal plate tissue. M30-positive cells in villous tissues were
      significantly increased in placentas from smoking mothers compared to nonsmoking
      mothers. When evaluated by the TUNEL method, the difference between the two
      groups of women was not significant. Our study shows that apoptosis was increased
      in the placentas of smoking mothers with growth-restricted infants. The
      difference between the two groups was mainly in the syncytiotrophoblast layer and
      in connection with perivillous fibrin deposition. Cigarette smoke with reduction
      in blood flow has previously been shown to increase apoptosis, and it is possible
      that this could be one of the mechanisms playing a role in the growth
      restriction.

PMID- 15568215
TI  - Acinic cell carcinoma: an unusual cause of bronchial obstruction in a child.
AB  - Primary acinic cell carcinomas of the lung are rare tumors, usually presenting in
      adulthood as parenchymal or endobronchial masses. These lesions are generally
      recognized by their morphological pattern and the presence of periodic acid
      Schiff (PAS)-positive, diastase-resistant cytoplasmic granules. We describe a
      case of pri-mary acinic cell carcinoma of the bronchus in a 4-year-old girl. The
      tumor has the typical acinar structures:weakly PAS-positive, diastase-resistant
      cytoplasmic granules and intra-acinar laminated calcific structures. A lobectomy
      was done with a clear bronchial resection margin. The child is well with no
      evidence of recurrence or metastasis 2 years postresection.

PMID- 15568216
TI  - Asteroseismology: oscillations on the star Procyon.
AB  - Stars are spheres of hot gas whose interiors transmit acoustic waves very
      efficiently. Geologists learn about the interior structure of Earth by monitoring
      how seismic waves propagate through it and, in a similar way, the interior of a
      star can be probed using the periodic motions on the surface that arise from such
      waves. Matthews et al. claim that the star Procyon does not have acoustic surface
      oscillations of the strength predicted. However, we show here, using ground-based
      spectroscopy, that Procyon is oscillating, albeit with an amplitude that is only
      slightly greater than the noise level observed by Matthews et al. using spaced
      based photometry.

PMID- 15568217
TI  - Drug company influence extends to nurses, pharmacists, and patient groups.

PMID- 15568218
TI  - Two test cases in Holland clarify law on murder and palliative care.

PMID- 15568220
TI  - Regional differences in rates of plant speciation and molecular evolution: a
      comparison between eastern Asia and eastern North America.
AB  - The eastern Asian (EAS)-eastern North American (ENA) floristic disjunction is one
      of the best-known biogeographic patterns in the Northern Hemisphere. Recent
      paleontological and molecular analyses have illuminated the origins of the
      biogeographic pattern, but subsequent diversification and evolution of the
      disjunct floras in each of the two continents after isolation remains poorly
      understood. Although similar in climate and floristic composition, EAS has twice
      as many species as ENA in genera occurring in both regions. Explaining such
      differences in species diversity between regions with similar environmental
      conditions (diversity anomalies) is an important goal of the study of the global
      patterns of biodiversity. We used a phylogenetic approach to compare rates of net
      speciation and molecular evolution between the two regions. We first identified
      EAS-ENA disjunct sister clades from ten genera (Asarum, Buckleya, Carpinus,
      Carya, Cornus, Hamamelis, Illicium, Panax, Stewartia, and Styrax) that represent
      diverse angiosperm lineages using phylogenetic analyses of ITS (internal
      transcribed spacer of nuclear ribosomal DNA) sequence data. Species richness and
      substitution rate of ITS between sister clades were compared. The results
      revealed a pattern of greater species diversity in the EAS counterparts. A
      positive relationship between species diversity and ITS substitution rate was
      also documented. These results suggest greater net speciation and accelerated
      molecular evolution in EAS. The data support the idea that a regional difference
      in net speciation rate related to topographic heterogeneity contributes to the
      diversity anomaly between EAS and ENA. The close relationship between rates of
      ITS evolution and species richness further suggests that species production may
      be directly linked to rate of nucleotide substitution.

PMID- 15568221
TI  - Acidogenic pretreatment of wastewaters containing 2-nitrophenol.
AB  - Anaerobic Toxicity Assay (ATA) tests were conducted on acidogenic cultures to
      assess the feasibility of using acidogenic processes to treat wastewaters
      containing 2-nitrophenol. Results indicated 2-nitrophenol could be removed with a
      removal efficiency of more than 98%. 2-aminophenol was identified as the major
      metabolite of the biotransformation of 2-nitrophenol. Reduction in inhibition
      potential of acidogenic pretreated effluent was observed in the aerobic process.
      EC50 values of 2-nitrophenol and 2-aminophenol were found to be 0.065 mM and 1.83
      mM respectively.

PMID- 15568223
TI  - Findings of scientific misconduct.

PMID- 15568224
TI  - Cytokine levels in bronchoalveolar lavage fluid and blood of neutropenic patients
      with pneumonia.

PMID- 15568225
TI  - Resistance to microtubule-targeted cytotoxins in a K562 leukemia cell variant
      associated with altered tubulin expression and polymerization.
AB  - A vinblastine resistant cell line, KCVB2, was established by co-selecting the
      parental erythroleukemic cell line K562 with step-wise increased concentrations
      of vinblastine (Velban) in the presence of the cyclosporin D analogue PSC 833 (2
      microM), a potent modulator of the multidrug resistance phenotype. KCVB2 cells
      are 8-fold resistant to the selecting agent, vinblastine, but also exhibit
      significant resistance to other vinca alkaloids, including 14-fold resistance to
      vinorelbine, as well as 6-fold cross-resistance to paclitaxel. Doubling time and
      morphology were similar to the parental K562 cells. Rt-PCR analysis revealed no
      alterations in the expression of the mdr1 and MRP genes. Intracellular
      vinblastine accumulation was unchanged. Disruption of the mitotic spindles and
      multiple mitotic asters occurred in both cell lines but required higher
      concentrations of vinblastine in KCVB2 cells than in K562 cells. Significant
      differences were observed in the tubulin content of KCVB2 cells: reduction of
      total tubulin content, increased polymerized fraction of total tubulin, and
      overexpression of class III beta-tubulin which is expressed at very low levels in
      the parental K562 cells. K562 cells transfected with murine class III beta
      tubulin did not display the resistance pattern observed in KCVB2 cells.
      Revertants of KCVB2 manifested reversion to parental drug sensitivity, an
      increase in total tubulin level, and a decrease in polymerized tubulin. In
      conclusion, the KCVB2 cell line displays a novel mechanism of resistance to both
      depolymerizing and stabilizing microtubule-targeted cytotoxins which does not
      involve altered cellular drug accumulation, but corresponds to alterations in the
      total tubulin content and polymerization status, and may involve an effect on
      microtubule dynamics.

PMID- 15568226
TI  - Treatment of peritoneal carcinomatosis in patients with digestive cancers with
      combination of intraperitoneal hyperthermia and mitomycin C.
AB  - Peritoneal carcinomatosis in patients with digestive cancer carries a poor
      prognosis, with a majority of patients dying within 6 months. Mitomycin C has
      been reported to have some antitumor efficacy in this setting. We performed
      combination intraperitoneal hyperthermia and mitomycin to potentiate the effect
      of mitomycin C in 83 patients with peritoneal involvement due to digestive
      cancers. Eighty six IPCH procedures were performed using inflow temperature 46 to
      49 degrees Celsius, using a closed circuit, during 90 minutes. Mitomycin C was
      administered as a perfusate at 10 mg/l. Primary tumors were essentially gastric
      (42) and colorectal (27). Mortality and morbidity rates were 3/83 and 5/83
      respectively. For resectable tumors, the median survival time was 16 months in
      stage 1 and 2 carcinomatosis (malignant granulations less than 5 mm in diameter).
      For resectable gastric cancers with stage 1 and 2 carcinomatosis, one, two and
      three year actuarial survival rates were 80, 61 and 41% respectively. In
      conclusion, IPCH appears to be an interesting therapeutic option in patients with
      digestive cancers and small malignant peritoneal granulations (stage 1 and 2).

PMID- 15568227
TI  - Ceramide : A New Target in Anticancer Research?
AB  - An astute observer of chemotherapeutic progress concedes that anticancer research
      is, in effect, often more empirical that rational, and there are those who
      maintain that little gain has been made in the therapeutic outcome of cancer
      patients in the past 60 years, thus, questioning the wisdom of continued
      expenditure of funds for research in cancer chemotherapy. Half a decade ago few
      would have denied the importance of regarding the intimate drug-target
      interactions in cell death or in resistance thereof. However, the heretofore
      parochial approach to drug screening and rationalization of structure-activity
      based on specific drug-target interactions has met with limited success. This
      standpoint has forced investigators to explore new and certainly provocative
      interpretations, which necessitate radical departure from accepted but perhaps
      outworn concepts of the action of drugs. The recent identification of a ceramide
      mediated apoptotic signaling pathway triggered by antitumor agents may offer new
      insights into mechanism of action of chemo- and radio-therapy. This review is
      intended to initiate a debate on the role of ceramide in apoptosis signaling: is
      it a consequence of cell damage, or part of an independent cytotoxic pathway ?

PMID- 15568228
TI  - Post-prandial hyperglycemia in type 2 diabetes mellitus, diabetic cornea
      neuropathy and beta hydroxyl butyrate in diabetic ketoacidosis.

PMID- 15568229
TI  - Longer stay, longer life.

PMID- 15568230
TI  - Evidence-based research, editors, facts, statistics, and manipulations.

PMID- 15568231
TI  - Variation in torque expression in preadjusted appliances.

PMID- 15568232
TI  - Treatment of missing lateral incisors.

PMID- 15568233
TI  - Protectionism and freedom of contract: the erosion of female autonomy in
      surrogacy decisions.

PMID- 15568234
TI  - Embryonic stem cell research: one small step for science or one giant leap back
      for mankind?
AB  - At the forefront of modern debate over the ethical use of biotechnology is
      embryonic stem cell research. In this poignant analysis of its legitimacy, the
      author examines the history of this research in light of the United States'
      policy favoring the protection of human beings over scientific progress. Stem
      cells, which can divide in culture to create specialized cells in the human body,
      possess significant potential for curing disease, particularly when taken from
      human embryos. However, as evidenced by the research atrocities committed under
      the Nazi regime, the benefits of human research do not come without a cost to
      humanity. Recognizing this, the later trial of these scientists produced the
      Nuremberg Code, a set of natural law principles guiding future research on humans
      that continues to influence health policy decisions. Drawing on this background,
      the author first considers the appropriate legal status for a human embryo.
      Biologically, the characteristics of a human embryo place it between human tissue
      and a constitutional person. Judicially, the answer is even less clear. The
      author analyzes case law in the context of abortion and in vitro fertilization,
      as well as classifications by the common law, state legislation, and the National
      Bioethics Advisory Commission, to conclude that a human embryo should be subject
      to the same legal and ethical restrictions as any other "human subject."
      Accordingly, the author argues that embryonic stem cell research violates the
      ethical standards and purposes of the Nuremberg Code and should be banned by
      federal legislation. Such a prohibition will fulfill the societal policy choice
      of protecting potential life and vulnerable human subjects.

PMID- 15568235
TI  - WHO launches new "5 keys" strategy to reduce the global incidence of foodborne
      disease.

PMID- 15568236
TI  - World Health Organization supports global effort to relieve chronic pain.

PMID- 15568237
TI  - Africa launches largest ever immunization campaign.

PMID- 15568239
TI  - World Health Organization, other UN agencies, build on momentum of World Health
      Day to improve global road safety.

PMID- 15568238
TI  - Stopping the invisible epidemic of maternal deaths.

PMID- 15568240
TI  - Malaria vaccine trial shows promising results.

PMID- 15568241
TI  - Joint statement WHO/UNDP: Indoor air pollution--the killer in the kitchen.

PMID- 15568242
TI  - Fetal surgery and wrongful death actions on behalf of the unborn: an argument for
      a social standard.

PMID- 15568243
TI  - The cloudy crystal ball: genetics, child abuse, and the perils of predicting
      behavior.

PMID- 15568244
TI  - Dr. Jekyll's waiver of Mr. Hyde's right to refuse medical treatment: Washington's
      new law authorizing mental health care advance directives needs additional
      protection.
AB  - Mental health care advance directives are gaining popularity nationwide.
      Following a growing trend, the Washington State Legislature has recently passed a
      law allowing patients to draft mental health care advance directives that could
      be irrevocable. Patients who sign an irrevocable directive essentially waive
      their fundamental right to refuse treatment in the future. The United States
      Supreme Court has held that waivers of fundamental rights must be made knowingly,
      voluntarily, and intelligently. However, as passed, Washington's new law contains
      insufficient safeguards to guarantee such a waiver. This Comment proposes that
      the Washington State Legislature amend this law the require two additional
      protections: a "rights advocate" to explain the potential waiver of rights, and a
      written warning in the advance directive form. These safeguards will help ensure
      that patients make knowing and intelligent waivers of their fundamental right to
      refuse treatment.

PMID- 15568245
TI  - When parental autonomy clashes with a child's interest in the advances of
      science: the case for the future of court-ordered gene therapy.

PMID- 15568246
TI  - Snowflake adoptions and orphan embryos: the legal implications of embryo
      donation.

PMID- 15568247
TI  - State v. Oakley: infringing on women's reproductive rights.

PMID- 15568248
TI  - Reproductive self-determination in the Third Circuit: the statutory proscription
      of wrongful birth and wrongful life claims as an unconstitutional violation of
      Planned Parenthood v. Casey's undue burden standard.

PMID- 15568249
TI  - [The clinical effects of hyperbaric oxygen therapy combined with supragingival
      and sublingual scaling therapy on periodontitis].
AB  - PURPOSE: This study was to observe the clinical effects of hyperbaric oxygen
      therapy combined with supragingival and subgingival scaling therapy on
      periodontitis. METHODS: The patients with periodontitis were divided randomly
      into 3 groups, the supragingival and subgingival scaling therapy group, the
      hyperbaric oxygen therapy group, the hyperbaric oxygen combined with
      supragingival and subgingival scaling therapy group. The clinical index and the
      level of aspartate aminotransferase in gingival cervical fluid (GCF-AST) of the 3
      groups were compared pre and post treatment,and the clinical index and the level
      of GCF-AST of the 3 groups after treatment were compared. RESULTS: The 3 methods
      had different clinical effects on periodontitis, and the hyperbaric oxygen
      combined with supragingival and subgingival scaling group had the best
      therapeutic results. CONCLUSION: The hyperbaric oxygen therapy combined with
      supragingival and subgingival scaling therapy had synergistic action on
      periodontitis.

PMID- 15568250
TI  - Bibliography. Current world literature. Diagnostics and techniques.

PMID- 15568251
TI  - Emerging scholarship in nursing.
AB  - These are dynamic times for nursing history in Canada, as this special issue of
      the Canadian Bulletin of Medical History demonstrates. Twenty years ago, scholars
      sought to create one professional identity and one homogenous historical story
      while current historians of nursing understand that profession to be more diverse
      and more complex. Emerging scholarship situates itself increasingly within
      mainstream histories and the subfield of women's history. The articles and book
      reviews represent a wide range of research interests and approaches, as well as
      regions outside of Ontario and central Canada. They reveal increasing diversity
      of primary sources, increasing use of analytical concepts, and fascinating new
      directions for analyzing practice as authors address questions such as: Who could
      legitimately claim to be a nurse, what is nursing practice, and what is health
      care? While these trends are encouraging, significant gaps remain in nursing
      historiography, and nursing practice continues to be ignored or marginalized with
      the wider body of health care historiography.

PMID- 15568252
TI  - The human rights of persons with mental disabilities: a global perspective on the
      application of human rights principles to mental health.

PMID- 15568253
TI  - [Antibiotic therapy in serious septic states].

PMID- 15568254
TI  - Monsters at the patent office: the inconsistent conclusions of moral utility and
      the controversy of human cloning.

PMID- 15568255
TI  - Roe and the new frontier.

PMID- 15568256
TI  - [Perioperative renal protection].

PMID- 15568257
TI  - Choosing the genetic makeup of our children: our eugenics past--present, and
      future?

PMID- 15568258
TI  - Resolving the unresolvable: the case of the conjoined twins.

PMID- 15568259
TI  - Race, health, and health care.

PMID- 15568260
TI  - Vanishing vaccinations: why are so many Americans opting out of vaccinating their
      children?
AB  - Vaccinations against life-threatening diseases are one of the greatest public
      health achievements in history. Literally millions of premature deaths have been
      prevented, and countless more children have been saved from disfiguring illness.
      While vaccinations carry unavoidable risks, the medical, social and economic
      benefits they confer have led all fifty states to enact compulsory childhood
      vaccination laws to stop the spread of preventable diseases. Today, however,
      vaccines are becoming a victim of their success--many individuals have never
      witnessed the debilitating diseases that vaccines protect against, allowing
      complacency toward immunization requirements to build. Antivaccination sentiment
      is growing fast in the United States, in large part due to the controversial and
      hotly disputed link between immunizations and autism. The internet worsens fears
      regarding vaccination safety, as at least a dozen websites publish alarming
      information about the risks of vaccines. Increasing numbers of parents are
      refusing immunizations for their children and seeking legally sanctioned
      exemptions instead, apparently fearing vaccines more than the underlying diseases
      that they protect against. A variety of factors are at play: religious and
      philosophical beliefs, freedom and individualism, misinformation about risk, and
      overperception of risk. State legislatures and health departments now face a
      difficult challenge: respecting individual rights and freedoms while also
      safeguarding the public welfare. Nearly all states allow vaccination exemptions
      for religious reasons and a growing number provide "philosophical" opt-outs as
      well. However, in all but a handful of jurisdictions, neither objection is
      seriously documented or verified. Often, the law requires a parent to do no more
      than simply check a box indicating she does not wish her child to receive
      immunizations. The problem is exacerbated by financial incentives schools have to
      encourage students to opt out of vaccinations. The rise in parents opting out has
      caused the AMA grave concern, with many experts decrying the rise of so-called
      "exemptions of convenience." In some areas, nearly one out of five children have
      not received their recommended vaccines. The consequences are serious not only
      for those unprotected children, but for the rest of society as well. "Herd
      immunity" is threatened as more and more parents free ride off of the community's
      dwindling immunity, and outbreaks of diseases thought to have been conquered have
      already occurred. Lawsuits against vaccine manufacturers threaten them with
      bankruptcy, costs are being externalized onto the healthcare and legal systems,
      and vulnerable populations are suffering harm or even death. In the interests of
      social welfare, state legislatures and health departments should consider methods
      to ensure that the exemption process is carefully tailored to prevent check-the
      box opt-outs of convenience, while still allowing exemptions for those with
      earnest and informed convictions or medical reasons.

PMID- 15568261
TI  - "They gave their care, but we gave loving care": defining and defending the
      boundaries of skill and craft in the nursing service of a Manitoba mental
      hospital during the great depression.
AB  - The School of Nursing at the Brandon Hospital for Mental Diseases was established
      in 1921 to equip the hospital with a corps of nurses equal to those found in
      urban general hospitals. While the school replicated the form of the general
      hospital training school, its credential was rejected by the national association
      of graduate nurses. Without the possibility of registration the mental nurses of
      the 1920s evolved a culture of resistance to the strictures of the training
      school, one which included affiliation with a trade union. Although still shut
      out by the general nursing community, the nurses of the 1930s, arriving with a
      different sense of their occupational and social mobility, were more disposed to
      embrace the professional ideology of the training school. By invoking their
      superior ability to care and their learned capacity to function in the
      unpredictable environment of the mental hospital, they constructed mental nursing
      as a skilled craft based on proprietary knowledge, different from the work of
      both the general hospital nurse and the untrained ward attendant.

PMID- 15568262
TI  - Parting at the crossroads: the emergence of education for psychiatric nursing in
      three Canadian provinces, 1909-1955.
AB  - Early in the 20th century, nursing emerged as an essential part of psychiatry's
      attempt to provide scientific care for insanity. Throughout Canada psychiatric
      nursing is a specialty of general or registered nursing. In Western Canada,
      however, it is also a separate and distinct profession known as registered
      psychiatric nursing (RPN). To further the study of nursing history, this paper
      examines the emergence and early development of mental hospital nursing in
      Canada, tracing the changing patterns of nurse training from 1909, when Ontario's
      asylum training school movement was established, to 1955, when education for
      psychiatric nursing split along the Manitoba-Ontario border into two models.
      Through case studies in three provinces (Ontario, Manitoba and Saskatchewan),
      this study examines the question of how Canadian psychiatric nursing developed
      into two entirely different models. During the 20th century, and interplay of
      social, political and economic factors emerged which shaped the development of
      psychiatric nursing and influenced the evolution of the two models. In addition,
      there were forces within nursing itself, including the effects of specific
      strategic decisions taken by nursing's leaders and the continuing role of nurses'
      resistance to the authority expressed by those within the medical profession. The
      development of psychiatric nursing is best understood by focusing on the point
      where psychiatry's authority intersected with the gendered limitations of
      nursing's leaders. This struggle represented a contest for control over education
      for mental hospital nursing. This paper argues that the turning point in the
      battle for control of Canadian education for psychiatric nursing occurred when
      nurse leaders refused to allow the specialty of psychiatric nursing to be taken
      over by an expanding psychiatric monopoly. The distinct psychiatric-controlled
      Western Canadian-style apprenticeship training was halted at the Manitoba-Ontario
      border. That nursing leaders persevered in the struggle to gain authority for
      psychiatric nursing education was a significant contribution to the development
      of Canadian nursing education and the psychiatric nursing specialty. Remnants of
      the themes found in the study endure to the present as organized nursing
      continues to struggle with issues around autonomy and authority over education
      and practice.

PMID- 15568263
TI  - "Monthly" nurses, "sick" nurses, and midwives in 19th-century Toronto, 1830-1891.
AB  - In the decades before formal training, nursing in English Canada was carried out
      by untrained women and a few men, of varying skill and respectability. Little is
      known of their lives. Using Toronto as a case study, this paper explores the
      development of nursing in the 19th-century city as a trade for working-class
      women. As Toronto grew and industrialized, opportunity grew for working-class
      women to nurse for pay. This paper considers the range of expertise and
      respectability of nurses working in city homes and hospitals, explores the fluid
      nature of nursing roles, and the changing definition of "nurse" over time.

PMID- 15568264
TI  - Blurring the boundaries of space: shaping nursing lives at the Red Cross outposts
      in Ontario, 1922-1945.
AB  - Historians and other scholars interested in the history of hospitals have
      investigated the links between medical architecture and the organization of space
      with the evolution of modern medicine. The transformation over time in the
      architectural for of medical institutions has tended to reflect developments in
      medical science and therapeutic efficiency as well as elements in the broader
      social climate. Some authors, however, have argued for the agency of structure
      and spatial organization, to consider that they are not just containers with
      which human activities take place, but which also actively construct or
      constitute social practices and relations. Most studies of this nature have
      centred on large medical buildings especially in urban areas, and have examined
      the impact of architectural arrangement in relation to administrators and
      architects, physicians and patients. Fe have considered the interconnections of
      form and space with nurses, despite the prominence of institutional nursing
      labour since the late 19th-century. The following discussion begins an
      exploration of these concepts within the rural environment. Between 1922 and
      1984, the Ontario Division of the Canadian Red Cross Society administered an
      outpost program in which it operated small hospitals and nursing stations in
      isolated communities throughout the northern reaches of the province. This
      article will focus primarily o n the one-nurse stations that the Division managed
      during the interwar years and the nurses that it hired to staff them. The
      interior spatial organization of these outposts, which led in particular to their
      multiple functions as tiny hospitals, community health centres and nurses' homes,
      not only shaped both the professional practice and the social or private lives of
      the Red Cross nurses but also contributed to the diffusion of contemporary
      precepts in health and medical care throughout a remote population.

PMID- 15568265
TI  - "We have worked while we played and played while we worked": discipline and
      disobedience at the Kingston General Hospital Training School for Nurses, 1923
      1939.
AB  - Drawing on evidence found in nurses' journals, oral accounts, yearbooks and other
      cultural productions as well as in hospital records, this paper considers the
      experiences of apprentices in a hospital nursing training school in the interwar
      period. By combining elements of scientific management with an older paternalist
      ethos, hospital administrators sought to imprint student nurse "material" with
      standards of work and behaviour valued by the hospital institution and the
      community that supported it. Students, whose expectations for nursing school
      often conflicted with those of management, developed a culture of mutuality that
      provided them with valuable resources to subvert and/or ameliorate the effects of
      disciplinary technologies and to re-appropriate the spaces and discourses of
      nursing training.

PMID- 15568266
TI  - Mapping the demise of the St. John Ambulance Home Nursing Program in Nova Scotia:
      1950-1975.
AB  - This paper maps the decline in Nova Scotia of a near-century old tradition of
      instruction in Home Nursing to members of the Nursing Divisions of the St. John
      Ambulance Brigade, and interested others, the majority women. The focus of this
      analysis is the period 1950-75. I argue that the gradual loss of program vitality
      is linked most directly to the changing and ultimately declining fortunes of the
      Brigade, These in turn are influenced by developments in the world beyond the
      organization, developments in health care in Canada and in the lives of Canadian
      women, who were the mainstay of membership. Through the Home Nursing program, a
      program to which the Canadian Nurses Association and Registered Nurses throughout
      Canada made a substantial contribution, the Brigade aimed to establish and
      maintain a reserve army of auxiliary nurses, for deployment when regular nursing
      services were over taxed. Successful in this endeavour during both world wars,
      the Brigade, a highly gendered and militarist organization, could not adapt to
      changes in both social attitude and social policy in postwar Canada. The demise
      of the Home Nursing program in Nova Scotia mirrors, if in a negative way, the
      emergence in Canada of a state-sponsored and hospital-focused health care system,
      and changing patterns in women's engagement in civic activities.

PMID- 15568267
TI  - NCQA report notes some health plan quality gains and major gaps.

PMID- 15568268
TI  - Report calls for nationwide effort to reduce childhood obesity.

PMID- 15568269
TI  - Postpartum home nurse visits improve infant health, reduce costs, report says.

PMID- 15568270
TI  - Use of database leads to improved outcomes for pediatric asthma patients.

PMID- 15568271
TI  - The material of practice: the Canadian Nursing History Collection.
AB  - The Canadian Nursing History Collection is a special holding of over 1500
      artifacts at the Canadian Museum of Civilization and the Canadian War Museum. The
      most significant of its kind, the collection includes uniforms, pins, diaries,
      instrument kits, and military medals. Researchers and the public will access the
      collection through an on-line catalogue, a major exhibition, and a book. The
      material culture of nursing represented by this collection provides nursing
      historians with a whole new body of evidence for insights into nursing history.
      The sample of hospital uniforms, from 1900 to the present, for example, raises
      new and theoretical approaches.

PMID- 15568272
TI  - Comment: DNA as property: implications on the constitutionality of DNA dragnets.

PMID- 15568273
TI  - Roe v. Wade and the common law: denying the blessings of liberty to our
      posterity.

PMID- 15568274
TI  - I teach you the superman: why Congress cannot constitutionally prohibit genetic
      modification.

PMID- 15568275
TI  - Practice parameter: diagnostic assessment of the child with cerebral palsy:
      report of the Quality Standards Subcommittee of the American Academy of Neurology
      and the Practice Committee of the Child Neurology Society.

PMID- 15568276
TI  - [Gender, religion and ethnicity: the history of Quebec nursing].

PMID- 15568278
TI  - Oratory and rhetoric in Renaissance medicine.

PMID- 15568277
TI  - Organizing practice: nursing, the medical model, and two case studies in
      historical time.
AB  - The medical model of clinical practice has long presented rather awkward
      challenges to the discipline of nursing. This study explores this challenge
      within nursing practice more deeply by examining two moments in the history of
      nursing practice: that before and that after the late 19th century
      professionalizing of the discipline. The first historical case study looks to the
      experiences of lay men and women staff caring for insane patients at the Friends
      Asylum in early 19th-century Philadelphia. This case study explores the workings
      of particular clinical encounters in day-today clinical practice. The second
      historical case study looks to the organizational efforts of pediatric nurse
      practitioners in the 1970s. This case study, set during a time when heuristic
      value of the medical model was already well-established, explores the tensions
      exerted by organized medicine and by organized nursing on the practicing nurse,
      and the efforts of both organizations to cloak their concerns surrounding
      professional legitimacy and control in the rhetoric of patient care and safety.
      These two seemingly disparate case studies suggest that the medical model has
      historically worked as an effective framework to contain the turmoil and
      turbulence that inevitably comes with the realities of both clinical practice and
      more organizationally focused disciplinary strategies. This study argues that the
      medical model has been an effective tool for thinking about all kinds and models
      of care for the sick. nurses appropriated the model to free them to do what they
      did best both before and after the development of modern models of practice.
      Hence, this study re-conceptualizes the medical model as both a source of power
      in nursing, and as a multidisciplinary, multidimensional organizational model of
      clinical and organizational practice.

PMID- 15568279
TI  - Heroic measures: Hippocratic medicine in the making of Euripidean tragedy.

PMID- 15568280
TI  - Genetic justice: discrimination by employers and insurance companies based on
      predictive genetic information.

PMID- 15568281
TI  - Who's your daddy (and mommy)? Creating certainty for Texas couples entering into
      surrogacy contracts.

PMID- 15568282
TI  - Involuntary treatment of the mentally ill: autonomy is asking the wrong question.

PMID- 15568283
TI  - Effect of recombinant human growth hormone and enteral nutrition on short bowel
      syndrome.
AB  - BACKGROUND: Studies showed that bowel rehabilitation therapy, including
      recombinant human growth hormone (rhGH), nutrition support, glutamine, and
      dietary fiber, promotes intestinal adaptation in patients with short bowel
      syndrome. The aim of the current study was to determine if enteral nutrition and
      rhGH are effective in weaning short bowel patients off total parenteral nutrition
      (TPN). METHODS: Thirty-seven patients with short bowel syndrome received bowel
      rehabilitation therapy for 4 weeks. Thirty-four patients were treated within 2
      years after short bowel syndrome. Treatment included nutrition support from
      enteral nutrition 500 to 1500 kcal/d, oral glutamine 0.6 g/kg/d, plus a high
      carbohydrate and low-fat diet. Once patients were in positive nitrogen balance,
      rhGH 0.05 mg/kg/d was administered for 3 weeks. RESULTS: All patients completed
      the treatment; there were no deaths caused by malnutrition. Intestinal absorptive
      capacity and plasma levels of proteins were significantly improved after
      treatment (p < .05). Of the 23 patients who have been followed for >2 years after
      bowel rehabilitation therapy, 21 patients (57%) weaned off parenteral nutrition,
      among which 18 (49%) patients lived on a high-carbohydrate and low-fat diet
      supplemented with enteral nutrition, and 3 patients were free of enteral
      nutrition and relied on high-carbohydrate and low-fat diet alone. The minimal
      intestinal length for these patients was 15 cm with ileocecal valve and intact
      colon in adults. CONCLUSIONS: Providing patients with enteral nutrition,
      glutamine, dietary fiber, and rhGH during howel rehabilitation therapy allows
      weaning from TPN in a sign;ficant number of patients.

PMID- 15568284
TI  - Elevation of asymmetric dimethylarginine (ADMA) in patients developing hepatic
      failure after major hepatectomy.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the
      arginine-nitric oxide pathway. It is conceivable that its concentration is
      tightly regulated by urinary excretion and degradation by the enzyme
      dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver.
      In rats, we showed a high net hepatic uptake of ADMA. Therefore, we aimed to
      confirm the role of the liver in humans and hypothesized elevated ADMA levels
      after major liver resection by a reduction of functional liver mass and injury to
      the remnant liver. METHODS: Patients undergoing a major hepatic resection (HEP, n
      = 17) or major abdominal surgery (MAS, n = 12) were included and followed in
      time. In addition, ADMA levels were measured in 4 patients having severe hepatic
      failure after a liver resection. Plasma ADMA concentration was measured by high
      performance liquid chromatography. RESULTS: Preoperatively and on days 1, 3, and
      5, plasma levels of ADMA were higher in HEP patients when compared with MAS
      patients. In HEP patients with prolonged (>7 days) hepatic injury, ADMA levels
      were especially elevated. On the first postoperative day, ADMA significantly
      correlated to bilirubin concentration (r = .528, p < .05) as a marker of
      postoperative hepatic function. Besides, in patients with severe hepatic failure,
      ADMA levels were highly elevated. CONCLUSIONS: In the present study, evidence was
      found for the role of the liver in the elimination of ADMA in humans. Increased
      levels of ADMA occur in the postoperative course after a major hepatic resection,
      especially when liver function is severely impaired. Further studies need to
      assess the role of ADMA in the development of complications after liver surgery.

PMID- 15568285
TI  - Observations on possible effects of daily vitamin K replacement, especially upon
      warfarin therapy.
AB  - Daily parenteral vitamin K supplement is now recommended by the U.S. Food and
      Drug Administration (FDA) for patients receiving IV hyperalimentation. This is
      considered as preferable to the previous recommendations of weekly parenteral or
      oral supplement, or as in some cases no supplement at all. Supplemental vitamin
      K1 will ensure adequate supplies for hepatic saturation and thus the production
      of clotting factors II, VII, IX, and X, plus the anticoagulants protein C,
      protein S, and protein Z. But this is not the entire story. This recommended
      supplement will affect other physiologic systems that also use vitamin K
      dependent gamma-carboxylation. Vitamin K is not 1 molecule but rather 2 natural
      substances, vitamin K1 and K2, and the synthetic K3's. It is not understood,
      what, if any, effect may occur because of the saturation or competition from the
      vitamin K1 upon the functioning of vitamins K2 and the derivatives of K3 in vivo
      upon bone mineralization, cell growth, and blood vessel health, all known to be
      influenced by the vitamins K. There are probably other physiologic systems yet to
      be studied relative to vitamins K and gamma-carboxylation. This review also
      considers the available research upon warfarin when given to patients receiving
      hyperalimentation and what effects the vitamin K supplements may have. Because
      studies to date have not controlled for vitamin K intake, consideration is given
      to whether one should expect any change in previously reported outcomes when
      using low-dose warfarin for prophylaxis against central vein thrombosis. Also
      considered are possible positive or negative effects that chronic warfarin
      therapy may have upon the other vitamin K-dependent systems under discussion.
      This review offers a platform for further discussion and derived clinical
      research provoked by this new FDA recommendation.

PMID- 15568286
TI  - Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and
      keratinocyte growth factor (KGF) on markers of gut adaptation after massive small
      bowel resection in rats.
AB  - BACKGROUND: Administration of specific growth factors exert gut-trophic effects
      in animal models of massive small bowel resection (SBR); however, little
      comparative data are available. Our aim was to compare effects of a human
      glucagon-like peptide-2 (GLP-2) analog, recombinant growth hormone (GH) and
      recombinant keratinocyte growth factor (KGF) on jejunal, ileal, and colonic
      growth and functional indices after 80% SBR in rats. METHODS: Thirty-seven male
      rats underwent small bowel transection (sham operation) with s.c. saline
      administration (control; Tx-S; n = 7) or 80% midjejuno-ileal resection (Rx) and
      treatment with either s.c. saline (Rx-S, n = 7), GLP-2 at 0.2 mg/kg/d (Rx-GLP-2;
      n = 8), GH at 3.0 mg/kg/d (Rx-GH; n = 8), or KGF at 3.0 mg/kg/d (Rx-KGF; n = 7)
      for 7 days. All groups were pair-fed to intake of Rx-S rats. Gut mucosal cell
      growth indices (wet weight, DNA and protein content, villus height, crypt depth,
      and total mucosal height) were measured. Expression of the cytoprotective trefoil
      peptide TFF3 was determined by Western blot. Gut mucosal concentrations of the
      tripeptide glutathione (L-glutamyl-L-cysteinyl-glycine) and glutathione disulfide
      (GSSG) were measured by high-performance liquid chromatography and the
      glutathione/GSSG ratio calculated. RESULTS: SBR increased adaptive growth indices
      in jejunal, ileal, and colonic mucosa. GLP-2 treatment increased jejunal villus
      height and jejunal total mucosal height compared with effects of resection alone
      or resection with GH or KGF treatment. Both GH and KGF modestly increased colonic
      crypt depth after SBR. SBR did not affect small bowel or colonic goblet cell
      number or TFF3 expression; however, goblet cell number and TFF3 expression in
      both small bowel and colon were markedly up-regulated by KGF treatment and
      unaffected by GLP-2 and GH. SBR oxidized the ileal and colonic mucosal
      glutathione/GSSG redox pools. GLP-2 treatment after SBR increased the
      glutathione/GSSG ratio in jejunum, whereas KGF had an intermediate effect. In
      addition, GLP-2 (but not GH or KGF) prevented the SBR-induced oxidation of the
      glutathione/GSSG pools in both ileum and colon. CONCLUSIONS: GLP-2 exerts
      superior trophic effects on jejunal growth and also improves mucosal glutathione
      redox status throughout the bowel after massive SBR in rats. Both GH and KGF
      increase colonic mucosal growth in this model. KGF alone potently increases gut
      mucosal goblet cell number and expression of the cytoprotective trefoil peptide
      TFF3. The differential effects of GLP-2, GH and KGF administration in this model
      of short bowel syndrome suggest that individual therapy with these growth factors
      may not be an adequate strategy to maximally improve adaptive gut mucosal growth
      and cytoprotection after massive small intestinal resection. Future research
      should address the use of these agents in combination in short bowel syndrome.

PMID- 15568287
TI  - Serum levels of interleukin-6 and C-reactive protein correlate with body mass
      index across the broad range of obesity.
AB  - BACKGROUND: It has been noted that elevated inflammatory markers, such as tumor
      necrosis factor-alpha (TNF), soluble TNF receptor II (sTNF-RII), interleukin 6
      (IL-6) and C-reactive protein (CRP), are characteristically found in the serum in
      obese patients. In this study, we examined the correlation of these markers with
      BMI in nonobese, obese, and morbidly obese individuals to explore this
      relationship across the broad range of obesity. METHODS: A total of 9 nonobese,
      including normal and overweight (body mass index [BMI] <30 kg/m2) and 41 obese
      (BMI > or =30 kg/m2) adults were included in this study. Among obese subjects, 11
      subjects were grade I or II obese (BMI > or =30 and <40 kg/m2), and 30 subjects
      were morbidly obese (grade III obese, BMI > or =40 kg/m2). Serum levels of
      glucose, insulin, TNF, sTNF-RII, IL-6, and CRP were measured. RESULTS: Obese
      subjects (BMI > or =30 kg/m2) had significantly higher serum levels of TNF, sTNF
      RII, IL-6, and CRP compared with nonobese subjects. Serum levels of sTNF-RII, IL
      6, and CRP, but not TNF, were positively correlated with BMI in obese subjects.
      However, in morbidly obese subjects, only the serum concentrations of IL-6 and
      CRP remained correlated with BMI, primarily because of this relationship in men.
      CONCLUSIONS: The present results support evidence that obesity represents an
      inflammatory state. In morbid obesity, the correlation of only IL-6 and CRP with
      BMI, particularly in males, suggests that IL-6 may be secreted in an endocrine
      manner in proportion to the expansion of fat mass particularly in the abdominal
      region, with a corresponding increase in hepatic production of CRP.

PMID- 15568288
TI  - Immune function is impaired with a mini nutritional assessment score indicative
      of malnutrition in nursing home elders with pressure ulcers.
AB  - BACKGROUND: Malnutrition is prevalent in elders with pressure ulcers and is
      associated with increased morbidity and mortality. This study compared
      nutritional status, assessed by the Mini Nutrition Assessment (MNA), to immune
      function in nursing home elders with pressure ulcers. METHODS: Nutritional status
      was assessed in nursing home residents (>65 years) with a stage II or more severe
      pressure ulcer. Subjects were classified as well nourished, at risk of
      malnutrition, or malnourished according to MNA score. Blood was drawn to assess
      whole blood mitogen-induced lymphocyte proliferation and neutrophil respiratory
      burst. Delayed-type hypersensitivity to 3 antigens was measured. MNA status was
      compared with immune parameters using the Kruskall-Wallis test. RESULTS: Of the
      24 subjects (23 men, 1 woman) who completed the study protocol, only 4 (17%) were
      classified as well nourished, whereas 7 (29%) were at risk and 13 (54%) were
      malnourished according to MNA score. Whole blood lymphocyte proliferation was
      significantly lower in the malnourished vs at risk subjects with both pokeweed
      (median [25th, 75th percentile], 0.6 [0.3, 0.9] vs 1.8 [1.2, 2.1] disintegrations
      per minute [dpm]/cell, p < .05); and concanavalin A (1.7 [0.9, 2.0] vs 2.8 [2.6,
      3.9] dpm/cell, p < .05) mitogens. Neutrophil respiratory burst normalized to a
      young control was significantly lower in malnourished subjects vs well-nourished
      subjects (0.8 [0.5, 0.9] vs 1.4 [1.0, 1.7], p < .05). Total induration to 3 skin
      test antigens was 13.4 +/- 4.6, 3.5 +/- 2.6, and 3.8 +/- 1.8 (mean +/- SEM) for
      well-nourished, at risk, and malnourished, respectively (p = .059). CONCLUSIONS:
      Immune function is impaired with an MNA score indicative of malnutrition in
      nursing home elders with pressure ulcers.

PMID- 15568289
TI  - Citrulline can preserve proliferation and prevent the loss of CD3 zeta chain
      under conditions of low arginine.
AB  - BACKGROUND: Arginine depletion by the enzyme Arginase I, decreases expression of
      the TCR zeta chain preventing T-cell activation and causing T-cell dysfunction.
      We hypothesized that citrulline could substitute for arginine under conditions of
      increased arginase expression. Thus, the goal was to establish a possible
      mechanism of how citrulline could overcome arginine depletion caused by arginase.
      METHODS: Jurkat cells were cultured, with or without arginase, in media
      containing different amino-acid constituents: complete RPMI containing arginine
      (C-RPMI) (arginine), Arginine-Free-RPMI (Arg-Free RPMI) and Citrulline-containing
      RPMI (Cit RPMI). Incorporation of citrulline was measured via uptake of 3H
      citrulline, whereas proliferation was measured via 3H-thymidine incorporation.
      zeta Chain was analyzed by 2-color flow cytometry. Argininosuccinate synthase
      (AS) and argininosuccinate lyase expression was detected using Northern blots, RT
      PCR, and Western blots. RESULTS: Jurkat cells exhibited a significant decrease in
      proliferation and 5 chain expression when cultured in the presence of arginase or
      in the absence of arginine. With citrulline, zeta chain expression and
      proliferation were maintained in the absence of arginine or in the presence of
      the enzyme arginase. Jurkat cells, cultured in the absence of arginine, were
      associated with a 5-fold increase in citrulline uptake. The absence of arginine
      was also associated with increased expression of AS. CONCLUSIONS: T cells exhibit
      the molecular capability of increasing citrulline membrane transport and up
      regulating AS expression, thus exhibiting the necessary mechanisms for converting
      citrulline into arginine and escaping the ill effects of arginine depletion.
      Therefore, citrulline has the potential to be a substitute for supplemental
      arginine in diseases associated with arginase-mediated T cell dysfunction.

PMID- 15568290
TI  - The C-terminal heptapeptide of bombesin reduces the deleterious effect of total
      parenteral nutrition (TPN) on gut-associated lymphoid tissue (GALT) mass but not
      intestinal immunoglobulin A in vivo.
AB  - BACKGROUND: Bombesin, the amphibian analog of mammalian gastrin-releasing
      peptide, reverses total parenteral nutrition (TPN)-induced atrophy of gut
      associated lymphoid tissue and increases intestinal and respiratory
      immunoglobulin A (IgA) levels. Structure-activity studies suggested that the
      biologically active portion of bombesin is a C-terminal heptapeptide (7AA). This
      study investigates the effect of 7AA on lymphocytes counts of the Peyer's patches
      (PP), the lamina propria (LP) and the intraepithelial layer (IE). METHODS: Forty
      eight male mice were randomized to receive chow (n = 13), TPN only (n = 9), TPN +
      15 microg 7AA 3 times per day (n = 13) or TPN + 150 microg 7AA 3 times per day (n
      = 13). After 5 days of feeding, PP, LP, and IE lymphocytes were determined.
      Intestinal IgA levels were measured with ELISA. Groups were compared with ANOVA.
      RESULTS: All TPN-fed mice lost more weight than mice fed chow (p < .04).
      Lymphocyte counts in PP, LP, and IE were significantly lower in the TPN group
      than in the 3 other groups but did not differ between the groups fed chow, TPN +
      15 microg 7AA 3 times per day, or TPN + 150 microg 7AA 3 times per day.
      Intestinal IgA levels were higher in chow-fed mice (148.4 +/- 16.9) than in mice
      fed TPN (98.4 +/- 14.0, p = .008), TPN + 15 microg 7AA 3 times per day (96.9 +/-
      7.7, p = .003) or TPN + 150 microg 7AA 3 times per day (87.3 +/- 6.7, p = .001).
      CONCLUSIONS: The C-terminal heptapeptide of bombesin prevented the TPN-induced
      decrease in intestinal lymphocyte populations but not the reduction in intestinal
      IgA levels.

PMID- 15568291
TI  - Urinary oxalate excretion increases in home parenteral nutrition patients on a
      higher intravenous ascorbic acid dose.
AB  - BACKGROUND: Vitamin C can be metabolized to oxalate. Case reports have suggested
      an association between IV vitamin C and urinary oxalate excretion. Recently, the
      US Food and Drug Administration required the dose of vitamin C in IV multivitamin
      preparations to be increased from 100 mg to 200 mg/d. We compared the urinary
      oxalate excretion level in stable home total parenteral nutrition (TPN) patients
      receiving both doses of vitamin C. METHODS: Each participant provided a 24-hour
      urine sample for oxalate determination on the vitamin C dose (100 mg/d), and
      again after at least 1 month on the increased vitamin C dose (200 mg/d). A 2-day
      diet diary was completed covering the day before and the day of the urine
      collection and was analyzed for oxalate and vitamin C content. Comparisons were
      made using Student paired t test and Wilcoxon signed rank. RESULTS: Thirteen
      patients (7 males/6 females) aged 63.1 +/- 12.2 years who had no history of
      nephrolithiasis and had received TPN for 55.9 +/- 78.8 months were enrolled. The
      most common indication for TPN was short bowel syndrome (38.5%). Eight patients
      had an intact colon. Urinary oxalate excretion increased on the 200-mg vitamin C
      dose, from 0.34 +/- 0.13 to 0.44 +/- 0.17 mmol/d (mean increase = 0.10 mmol/d; p
      = .04; 95% confidence interval 0.004 to 0.19 mmol/d). Oral intake of vitamin C
      and oxalate did not differ between the 2 collection periods. CONCLUSIONS: In
      therapeutically used doses, IV vitamin C increases urinary oxalate excretion,
      potentially predisposing susceptible individuals to nephrolithiasis. This factor
      should be considered in patients receiving home TPN.

PMID- 15568292
TI  - Effects of carrier solution on insulin bioavailability.
AB  - BACKGROUND: The aim of our study is to assess the influence of the base solution
      on the availability of biologic insulin expressed in the value of total insulin
      using the radioimmunoassay method and to monitor the influence of the base
      solution on the total insulin concentration over time. METHODS: Total insulin in
      a saline and in a total nutrient admixture was measured using the RIA method. In
      15 experiments, the application of the saline by a perfusor (8 IU Actrapid HM,
      100 IU/1 mL + 20 mL saline) was carried out at time intervals of baseline, 5, 10,
      30, 60, 90, and 210 minutes. The application of the total nutrient admixture (8
      IU Actrapid HM + 20 mL total nutrient admixture) was carried out in the same way.
      The MANOVA, ANOVA and paired t test with Bonferroni correction were then used for
      statistical evaluation. RESULTS: The average values of insulin concentration in
      saline at given time intervals were 21.5 +/- 11.3 mIU/L (5.4% of the
      theoretically calculated concentration). The level of insulin in the total
      nutrient admixture did not change over time, and it reached the values of 115.2
      +/- 22.3 (28.8% of the theoretically calculated concentration). Changes in
      insulin concentration in time were found only in the saline (ANOVA time effect p
      < .001 for saline; p = .26 for total nutrient admixture). CONCLUSIONS: The
      availability of insulin was significantly higher in the total nutrient admixture
      solution than in the saline in the 3.5-hour experiment. The dependence of insulin
      concentration on time is present only in saline, and the main changes in insulin
      bioavailability are within first 60 minutes. The difference could be caused by
      smaller insulin absorption to the syringe walls and to the set, owing to the
      amino acids in the mixture. The question whether the amino acid concentration
      affects insulin bioavailability stays opened to other studies.

PMID- 15568293
TI  - Standard equations are not accurate in assessing resting energy expenditure in
      patients with amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To assess the utility of standard equations for calculating caloric
      requirements in patients with amyotrophic lateral sclerosis (ALS). BACKGROUND:
      Malnutrition substantially increases the risk of death in ALS. Weight loss can be
      stabilized and survival prolonged with early gastrostomy feeding. However the use
      of standard nutrition equations has not been validated in this population. We
      therefore compared measured caloric expenditure to 2 predictive equations in
      patients with varying stages of ALS. METHODS: Thirty-four patients were studied.
      Caloric expenditure and respiratory quotient (R) were measured using indirect
      calorimetry. Results were compared with the Harris-Benedict equation. RESULTS:
      The prediction error for the Harris-Benedict equation was 18.6 + 14.9%. Limits of
      agreement showed this equation could overestimate caloric expenditure by 591
      kcal/d and underestimate requirements by 677 kcal/d. R was >0.86 in 11 patients,
      suggesting overfeeding, and <0.8 in 15 patients, suggesting underfeeding. The
      difference between predicted and measured caloric expenditure did not correlate
      with disease severity, disease duration, or body mass index. Mechanically
      ventilated patients had higher than predicted energy expenditure. CONCLUSIONS: We
      found that standard equations used to calculate energy expenditure were not valid
      for patients with ALS. Moreover, the majority of our patients were either overfed
      or underfed. As underfeeding can cause diaphragm impairment, and overfeeding can
      increase ventilatory load, indirect calorimetry should be considered in ALS
      patients to determine optimal caloric requirement.

PMID- 15568294
TI  - Glucose in parenteral nutrition: a survey of U.S. medical centers.
AB  - BACKGROUND: A previous report suggested that glucose administration in total
      parenteral nutrition (TPN) should not exceed 4 mg/kg/min with a respiratory
      quotient (RQ) >1.0. This rate would not be exceeded, in most patients, with a TPN
      glucose concentration of 15%. Our previous survey of hospitals, 7 years ago, of
      TPN composition revealed use of excessive glucose. Our purpose was to reevaluate
      glucose usage in TPN. METHODS: A subset of data from 45 hospitals participating
      in Novation's Medication Use Evaluation program, "Parenteral Nutrition for Adults
      and Neonates" study, was analyzed to document glucose administration in TPN.
      RESULTS: Data of 629 adult patients from 44 hospitals receiving TPN were
      analyzed. Of these, 30 hospitals with 478 patients had 100 patients (15.9% of the
      total) with TPN glucose infusion rates >4 mg/kg/min, whereas 27 hospitals, or
      61%, had average TPN glucose concentrations above 15%. This could be associated
      with an RQ >1.0, implying increased net lipogenesis. CONCLUSIONS: The majority of
      hospitals surveyed were found, as in a previous survey, to be using amounts of
      glucose in TPN which would be expected to be associated with an RQ >1.0, implying
      increased net lipogenesis.

PMID- 15568295
TI  - Drug trials.

PMID- 15568296
TI  - Safe practices for parenteral nutrition.

PMID- 15568297
TI  - Development and validation of the BSP-BPH (Bononian Satisfaction Profile--Benign
      Prostatic Hyperplasia) a "disease-specific" questionnaire for the evaluation of
      health related quality of life in patients with benign prostatic hyperplasia.
AB  - OBJECTIVES: Lower Urinary Tract Symptoms (LUTS) associated to Benign Prostatic
      Hyperplasia (BPH) are very common in middle aged and older men. Since BPH, and
      the related therapies have a significant impact on a patient's Quality of Life
      (QoL), the health related quality of life (HQoL) evaluation is becoming an
      important aspect to be considered. The present study deals with the development
      and validation of a BPH disease specific questionnaire (Bononian Satisfaction
      Profile - BSP-BPH), considering HQoL in patients seeking medical help for BPH.
      The innovation of this questionnaire is that the patients' scores achieved are
      related to their subjective satisfaction. MATERIALS AND METHODS: Questionnaire
      development: On the base of our previous experience with BSP-PC (a disease
      specific questionnaire assessing HQoL in prostate Cancer patients), of a careful
      review of other available instruments (SAT-P, SF-36, ICS-QoL, BPH-HqoL) and of
      three subsequent meetings with experts (10) and patients (20), we defined the ten
      life aspects mostly impaired by BPH. We created a first 72-item version of the
      BSP-BPH. Ten patients cross matched for age end education to our study population
      were asked to fill in the questionnaire. A 31 item questionnaire version,
      together with EuroQoL, an already generic validated instrument, was administered
      to 121 patients as well. Further meetings and statistical analysis defined the 18
      items of the BSP- BPH. Questionnaire validation: the BSP-BPH was filled in by 435
      patients enrolled in a campaign for detection of prostatic diseases held among
      the male population of Bologna. RESULTS: Questionnaire development: the
      participants' mean age was 63 years (N = 121); 47.1% had BPH. The 18 items were
      selected on the basis of the following criteria: a) r > 0.50, p < 0.05
      (correlation test re-test); b) p < 0.05 (ANOVA presence vs absence of BPH); c) r
      > 0.50, p < 0.05 (correlation with EuroQol). Questionnaire validation: the
      participants' mean age was 63 years (N = 436). 16 patients with a history of
      neoplasia were excluded from our study. 21 were missing data. 45% of the sample
      had BPH. Principal component analysis identified 5 components: 1) satisfaction
      about sexual functionality (Cronbach alpha = 0.94); 2) satisfaction about social
      functionality (alpha = 0.80); 3) satisfaction about cognitive/emotional
      functionality (alpha = 0.82); 4) satisfaction about urinary functionality (alpha
      = 0.87); 5) satisfaction about physical functionality (alpha = 0.66); total
      Cronbach alpha was 0.88. CONCLUSIONS: The 18 items version of BSP-BPH
      questionnaire can be used as an instrument for HQoL evaluation in patients with
      BPH focusing on patients' subjective satisfaction. At the moment only the Italian
      version is available.

PMID- 15568298
TI  - Power Doppler ultrasonography (PDU) as an additional tool to increase reliability
      of systematic biopsy of the prostate: a brief evaluation.
AB  - PDU is currently being tested as an aid to diagnosing prostate cancer. Our
      attempt has been to verify its usefulness to improve effectiveness of eight core
      TR biopsy. Two groups of patients were examined for increased PSA with or without
      a palpable prostatic nodule. The first group was composed by 52 patients between
      55 and 83 years of age (mean 69.57) with PSA values between 0.87 and 94.91 ng/ml
      (8.085 +/- 14.056) of which 29 (55.75%) showed a palpable nodule. All patients
      underwent prostatic eight core TR echobiopsy. The second group was composed by 56
      patients between 49 and 84 years of age (mean 69,19) with PSA values between 1.14
      and 59.7 ng/ml (8.74 +/- 12.977) of which 33 (58.97%) showed a palpable nodule.
      This group of patients underwent a PDU just before TR biopsy in order to assess
      prostatic blood supply and locate possible alterations. Prostatic volume in both
      groups was never higher than 50 cc. Of the first group 25 patients (48.08%) were
      prostate cancer positive. Of the second group 31 patients (55.36%) were positive
      to a biopsyfor prostate cancer. In addition 22 out of the 31 showed a palpable
      nodule and vascular irregularity. PDU is being tested in order to reduce the
      number of biopsies and tissue samplings. The above results (tests carried out by
      the same operator with two homogeneous groups of patients) show how PDU was
      useful in diagnosing a higher number of prostate cancers. We could therefore
      safely conclude that the use of PDU in association with TR biopsy greatly
      increases diagnostic sensitivity and specificity.

PMID- 15568299
TI  - Dermatofibrosarcoma protuberans of the urinary bladder: a case report.
AB  - The Authors reported a case of dermatofibrosarcoma protuberans of the urinary
      bladder in a 17-year old boy. The biology of this unusual urinary tumor is
      discussed.

PMID- 15568300
TI  - Orthotopic ileal neobladder giant stone in a female.
AB  - This article describes an unexpected case of a giant neobladder stone in a female
      that was diagnosed incidentally for a concurrent ovarian disease, without
      clinical or instrumental evidence of neobladder over distension. In July 1989,
      M.A., woman, 39-years old, underwent radical cystectomy, saving the uterus and
      the ovaries, and orthotopic ileal bladder substitution. Twelve years later she
      had symptoms of diffuse abdominal discomfort for about one month, without
      noticeable urinary symptoms or urinary retention. Enhanced CT and a subsequent
      MRI showed the presence of a 10 x 12.5 x 19 cm capsulated ovaric mass with sharp
      edges and associated obstructive bilateral hydroureteronephrosis, and an oval
      shaped stone with a 10 cm longitudinal diameter, which occupied the majority of
      the neobladder cavity. The patient underwent surgical operation to remove the
      ovaric mass (fibrotecoma) and to extract the giant floating stone by a
      neocystotomy. Its dimensions were 10.5 x 7 x 7 cm, weighing 760 g. The stone was
      triple phosphate on chemical-physical analysis. The case reveals that neobladder
      stones can be associated with very few symptoms and if an appropriate follow-up
      is not performed they can become of remarkable dimensions.

PMID- 15568301
TI  - Embolization of a hypoplastic kidney with a vaginal ectopic ureter in a case of
      pseudo-incontinence.
AB  - Ureteral ectopy into the vagina is a cause of pseudo-incontinence. When the
      corresponding kidney has a good function, the treatment of choice is the ureter
      reimplantation, otherwise the alternative is partial or total nephrectomy. To
      report a case of 18-year-old girl presented with urinary leakage occurring
      between normal voids that at 11-year-old was found to have, at cistoscopy and
      vaginoscopy, an left ureteral ectopy into the vagina with a non demonstrable
      corresponding kidney at conventional intravenous urography, dimercaptosuccinic
      acid scintigraphy and ultrasonography. Moreover the right kidney was found
      enlarged but normally located. Her parents refused the explorative laparotomy to
      localize and to remove the left kidney. We completed the examination with
      computed tomography that revealed a small hypoplastic and ectopic left kidney
      located at L4 level. Because the contribution of the hypoplastic kidney to the
      total renal function was insignificant, we decided to eliminate it. A selective
      embolization of the left renal artery was performed using polyvinyl alcohol foam.
      The pseudo-incontinence stopped immediately after The patient was discharged home
      in II postoperative day and has been free from any leakage for 3 years. Serum
      creatinine levels and blood pressure returned to their normal values.

PMID- 15568302
TI  - Leiomyoma of the epididymis and testicular adnexa: apropos of 3 cases.
AB  - The intrascrotal benign tumours are rare and are generally defined as arising
      between didymis and spermatic cord. Among the benign tumours of the epididymis
      and testicular adnexa, leiomyoma is second most common. Three cases of
      intrascrotal leiomyoma are reported: two originating from the epididymis and one
      from the epididymis and tunica vaginalis.

PMID- 15568303
TI  - Metanephric adenoma: case report and review of the literature.
AB  - Metanephric adenomas are benign tumors frequently found post-mortem (from 7% to
      22% of autopsies) which originate from distal tubules; they are generally small
      in dimensions (smaller than 1 cm) and located in the renal cortex. Etiology is
      unknown, even though they could be associated with smoke, tubular
      nephrosclerosis, dialysis. An endocrinal relationship was proposed, because of
      its more frequent incidence in female (2:1). Metanephric adenoma is an uncommon
      kind of renal adenoma with no malignant potentiality: from the clinical and
      diagnostic viewpoint its own greater importance depends on the probability of
      diagnostic misunderstanding with Wilms' tumor; furthermore its echographic,
      tomographic and arteriographic characteristics are often similar to small renal
      adenocarcinoma ones (100). Polycytemia is frequently associated to metanephric
      adenoma as paraneoplastic syndrome and, more rarely, abdominal mass, abdominal
      pain, hematuria and hypertension (140). The most important study on metanephric
      adenoma is the one realized by E.K. Mostofi, including 50 cases from the
      Department of Genitourinary Pathology, Armed Forces Institute of Pathology,
      Washington, D.C., published in 1995; in this study half of findings was
      incidental; mean dimension of tumor about 5,5 cm and in 50% it could be seen a
      distinct capsule sourrounding the tumor (in the remaining cases the capsule was
      discontinuos or absent) (210). An important radiological characteristic is that
      metanephric adenomas are more frequent calcificated than other histotypes and,
      from the pathological viewpoint, the most important differential element seems to
      be the smaller dimensions of its cells with hyperchromatic nuclei in the absence
      or lack in mitotic activity and in the absence of chromosome aberrations. In the
      case of difficult histological diagnosis, cytogenetic and immunohistochemical
      analysis can be useful. In conclusion, because it is impossible to distinguish in
      the preoperatory between the metaneprhic adenomas and the other tumoral types on
      the bases of the symptoms, dimensions or radiographic appearance, it is mandatory
      to treat it as malignant eteroformations in a therapeutical strategy, when it is
      possible.

PMID- 15568304
TI  - Could be ureteral endometriosis considered a symptomatic and severe urological
      disease?
AB  - Ureteral endometriosis is a rare localization of gynecological disease. We
      presented a case of left ureteral endometriosis in a 30-year-old woman with left
      abdominal pain and a radiological nonfunctioning kidney. Surgical treatment with
      ureteral resection and uretero-uretero anastomosys was conducted. Pathological
      examination of surgical specimen revealed endometriosis. The diagnosis of
      ureteral endometriosis should be considered in women with renal symptoms of
      noncalculous obstruction, particularly in premenopausal women with an anamnesys
      of polycistic ovary disease (POD) or severe menstrual related symptoms, although
      the disease is often strictly associated with silent renal obstruction. Only a
      high index of suspicion and the radiological support may help the urologist to
      obtain a early diagnosis. Early detection and prompt treatment strategy, surgical
      too, are extremely important to relieve symptoms and preserve renal function. The
      literature was reviewed.

PMID- 15568305
TI  - Cystinuria: definition, epidemiology and clinical aspects.
AB  - Cystinuria ia an inheritable autosomal recessive disorder of amino acids
      transport affecting the epithelial cells of the renal tubules and
      gastrointestinal tract. It is characterized by abnormal concentrations of cystine
      and the other dibasic amino acids in the urine, resulting in a risk of renal
      stone formation because of the low solubility of cystine in urine. According to
      the recent advances in molecular genetics, two genes have been identified as
      responsible for this disease (SLC3A1 and SLC7A9), but other unknown genes may be
      involved in cystinuria. We assessed the presence of cystinuria in 2086
      consecutive patients with renal stones by using cyanide-nitroprusside test
      (Brand's test). According to our experience, this screening test should be
      performed in all patients at the onset of renal stone disease in order to avoid a
      delay in the possible diagnosis of cystinuria. In fact cystinuric patients often
      have mixed calculi composed of substances other than cystine that can disguise
      the presence of cystininuria that is so diagnosed many years after the onset of
      the initial symptoms. Patients with positive cyanide-nitroprusside test were
      further studied for identification of urine amino acids by quantitative ion
      exchange chromatography. Pathological cystinuria was confirmed in 39 (1.9%) out
      of 41 patients with positive Brand test. The mean age of cystine stone patients
      was 38.1 +/- 15.8 years, whereas the age at stone onset was 21.8 +/- 12.4. Renal
      stones were recurrent in 85% of cases, while other 6 patients were observed at
      their first stone. The male to female ratio was 1:0.62. The mean number of stone
      episodes for patient was 18.5 +/- 35.8 and the mean interval to first recurrence
      was 4.1 +/- 4.3 years. The recurrence rate 5 years after the first renal stone
      was 83%. Furthermore we studied 85 members from 24 families of patients with
      cystine stones. Twenty-four family members excreted excessive amounts of cystine,
      but only 5 of them (21%) had cystine calculi. Twenty-two patients were treated
      with 1-1.5 g alpha-mercaptopropionylglycine daily. Treatment reduced stone
      formation from 0.93 to 0.46 stones/patient/year. Only six patients had side
      effects of sufficient severity to require withdrawal.

PMID- 15568306
TI  - Epidemiology, clinical features and treatment of idiopathic retroperitoneal
      fibrosis: our experience.
AB  - Retroperitoneal fibrosis (RF) is an uncommon disease with an estimated incidence
      of 1 case on 200.000 inhabitants. Idiopathic RF (2/3 of cases) must be
      distinguished from secondary RF, caused by hexogen substances assumptions,
      radiotherapy and various diseases. The treatment of RF is not yet univocally
      defined. From 1984 to 2002 we observed 15 patients (1 case with idiopathic
      retroperitoneal fibrosis) i.e. 27 ureteral units (1 patient was previously
      nephrectomized and 2 showed a monolateral ureteral involvement). The mean age was
      55 and the male:female ratio was 0.66:1. The commonest presenting symptoms were
      acute renal failure or renal colic. 14 patients needed preoperatory urinary
      drainage by nephrostomy or ureteral stenting. 6 patients were treated with
      steroids or tamoxifen without response so that all the 15 patients underwent
      surgery. 6 patients were lost to follow-up after 8 months while the other 9
      underwent clinical and radiological controls for a mean time of 84 months (range
      12-168) with evidence of normal canalization or steady dilatation of the
      excretory system for 8 of them. 1 patient developed a relapsing ureteral stenosis
      after ureterolysis and intraperitonealisation and needed ureterectomy with ileal
      interposition. In a case with monolateral presentation a controlateral stenosis
      was evidenced 5 years later. According to literature data, the surgical technique
      that ensured us the best results was ureterolysis with omental wrapping of the
      ureter. In our experience, medical treatments gave poor outcomes. However, in
      consideration of the low incidence of RF, perspective and multicentric studies
      are necessary to establish which is the most suitable treatment for each patient.
      Follow-up must be extended in patients with monolateral presentation to
      precociously reveal a possible contralateral involvement.

PMID- 15568307
TI  - Interstitial cystitis.
AB  - Interstitial cystitis (IC) is still considered a rare disease, but in the future
      its incidence will probably be revised if tendency is that of considering
      interstitial cystitis on the basis of clinical rather than endoscopic
      histological criteria. According to some urologists, cystodistension and vesical
      biopsy, even if not pathognomonic, are still effective up till now, at least for
      their prognostic-therapeutic value as well. If on one hand in the diagnosis of
      this condition symptoms tend to be of more and more value unlike instrumental
      investigations, on the other hand little has changed in therapy.

PMID- 15568308
TI  - Congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition
      characterized by an insufficient production of cortisol and mineraloactive
      hormones with a consequent hyperstimulation of hypothalamo-pituitary-adrenal
      feedback and an increase of androgens. Although the lack of different enzymes in
      adrenal steroidogenesis can be responsible for different forms of the disease,
      the deficiency of 21-hydroxylase is the more frequent defect. It is caused by
      mutations in CYP21 gene located on the short arm of chromosome 6 and it causes a
      heterogeneous phenotype characterized by a classical form (genitalia virilization
      in female, early onset acute adrenal insufficiency with salt wasting, precocious
      pseudopuberty, signs of hyperandrogenism), or by a simple virilizing form
      (presence of signs of hyperandrogenism without salt-loosing crises) or by a non
      classic form evidenced only by mild to moderate signs of hyperandrogenism. The
      diagnosis can be made by 17-hydroxyprogesterone measurement in basal and after
      ACTH stimulation test. Glucocorticoid and mineraloactive therapy have been proved
      to reduce the risk of adrenal crisis reducing the levels of androgens and
      controlling the symptoms of the disease.

PMID- 15568309
TI  - [Tobacco smoking and education].
AB  - Based on his performed study, the author describes that the spread of tobacco
      smoking depends on the level of education in different age- sexual groups in the
      Samara urban population.

PMID- 15568310
TI  - [Frequency and pattern of adverse reactions due to treatment of patients with
      pulmonary tuberculosis with antitubercular reserve drugs].
AB  - Two hundred and fifty-four patients with pulmonary tuberculosis, treated with
      reserve antituberculous drugs due to multidrug resistance, the ineffective prior
      stage of treatment, or intractable adverse reactions, were examined.
      Aminoglycosides and capreomycin were administered. Combinations simultaneously
      included 5-7 drugs. Adverse reactions were developed in 72.8% of the patients to
      different drugs and in different periods. Adverse gastrointestinal, renal,
      central nervous system, and auditory reactions of reserve drugs were most
      commonly detected. Essential were also electrolyte metabolic disturbances,
      hypothyroidism (when reserve drugs were given), intestinal dysbacteriosis, and
      allergic reactions. The paper analyzes the pattern of adverse reactions caused by
      each preparation, the time of their occurrence, and methods for their elimination
      in detail. Adverse reactions to reserve drugs exerted a negative effect of the
      efficiency of the chemotherapy performed.

PMID- 15568311
TI  - [Leukinferon in combined therapy for acute pulmonary tuberculosis].
AB  - Experiments on 140 CBA and C57BL/6 mice and studies of 163 patients with acute
      pulmonary tuberculosis have indicated that leukinferon has a immunomodulating
      effect on morphological reactions in the lung and on the clinical course of the
      disease. They have shown that leukinferon plays an important role in the
      activation of exudate macrophages and in the acceleration of their
      differentiation in experimental tuberculosis and that there is a rapid
      elimination of Mycobacterium tuberculosis from the involved organs without
      production of the L-forms of the causative agent when immunomodulation is used.
      At months 2-3, the patients with acute pulmonary tuberculosis showed the
      accelerated processes of detoxification, abacillation, infiltrate resolution, and
      decay cavity closure during hemo- and immunomodulation with the normalized
      production of cytokines (gamma-interferon and tumor necrosis factor-alpha).
      During 6-month therapy, a severe pulmonary process was arrested in 84% of cases
      and some patients were operated on (76% in the comparison group). The
      morphological effect of leukinferon was to increase mononuclear infiltration and
      to normalize a lung connective tissue response, by further decreasing the rate of
      inflammation.

PMID- 15568312
TI  - [Comparative evaluation of therapeutic effects of 3 and 4 antitubercular agents
      at the initial stage of the treatment of renal tuberculosis].
AB  - Three groups of the parameters of the therapeutic effects of 3 and 4
      antituberculous drugs on renal tuberculous inflammation were identified. The
      primary effect of 4 drugs was much frequently manifested itself by the
      normalization of urinalysis and the transfer of cultured to uncultured
      Mycobacterium tuberculosis (MBT). The equivalent effect of 3 and 4 drugs was
      characterized by the similar rate of continuation of specific mycobacteriuria, by
      the detection of MBT in the cavernous contents from the removed tuberculosis
      afflicted kidney and by the equivalent morphological characteristics of
      tuberculous inflammation involution. The negative impact of the therapeutic
      action of 4-component chemotherapy appeared as a much larger number of cases of
      intolerance of antituberculous drugs, hepatic and renal failures, and toxic-and
      allergic reactions.

PMID- 15568313
TI  - [Production of gamma-interferon by blood mononuclear cells in patients with
      various types of a tuberculous process].
AB  - To elucidate the diagnostic value of gamma-interferon (gamma-IFN) in the human
      body, the gamma-IFN production that was spontaneous and induced by BCG
      Mycobacterium bovis in the supernatants of short-term cultures of peripheral
      mononuclear cell from 31 patients with active tuberculosis was studied. The
      sandwich method of enzyme immunoassay was used, by employing two monoclonal
      antibodies in the avidin-biotin system. The studies have established the low
      spontaneous production of gamma-IFN in patients with the severe progressive
      course of a tuberculous process (22.5 +/- 2.5 pg/ml in Group 1 versus 41.5 +/-
      8.6 pg/ml in patients with the favorable course of a tuberculous process (Group
      2) and 34.0 +/- 3.5 pg/ml in healthy individuals (Group 3); p(1-2) < 0.05 and p(1
      3) < 0.05)). Moreover, there was a reduction in the induced production of gamma
      IFH in response to BGC (37.7 +/- 33.4 pg/ml in Group 1 versus 214.9 +/- 81.9
      pg/ml in Group 2 and 206.0 +/- 31.1 pg/ml in healthy individuals; p < 0.05 and
      p(1-3) < 0.001), which is of diagnostic and prognostic values.

PMID- 15568314
TI  - [Significance of determination of antituberculous antibodies by enzyme
      immunoassay in the diagnosis of pulmonary tuberculosis].

PMID- 15568315
TI  - [Surgical treatment of patients with acute pulmonary tuberculosis].
AB  - The immediate and late outcomes of treatment of acute pulmonary tuberculosis with
      and without surgical treatments (337 and 271 patients, respectively) were
      analyzed. The vast majority of patients in both groups were those with caseous
      pneumonia and fibrocavernous tuberculosis complicated by caseous pneumonia. A
      complete clinical effect was achieved in 14% of non-operated patients at their
      discharge, with a hospital mortality of 15.5%. A surgical treatment provided a
      6.5-fold early effectiveness with a less (8.6-fold) hospital mortality. In a
      follow-up periods (up to 11 years), the number of cases of recurrences and
      progression of tuberculosis in patients in whom surgery was indicated, but non
      operated cases was 5.7 times higher than that in those radically and arbitrarily
      radically operated on; 5-, 7-, and 10-year survival rates in the non-operated
      patients were 1.6, 2.3, and 4.9 times less, respectively (85.7% versus 17.6%).

PMID- 15568316
TI  - [Rationale for the tactics and a scale of surgical intervention for bilateral
      pulmonary hydatid disease].
AB  - The authors of this study have examined some experience gained in surgically
      treating 151 patients with bilateral pulmonary hydatid disease in 1991 to 2001,
      i.e. over 11 years. The examinees were divided into 7 groups. A hundred and forty
      patients underwent 205 surgical interventions. With this, organ-preserving
      operations and resections were made in 198 and 7 cases, respectively.
      Postoperative complications were observed in 12 cases. There were 3 fatal cases
      in the postoperative period.

PMID- 15568317
TI  - [The levels of T lymphocytes and thymic peptide antibodies in patients with
      infiltrative pulmonary tuberculosis and in those with cancer diseases].
AB  - A relationship of the levels of thymic peptide antibodies to those of the
      population and subpopulations of T lymphocytes was studied in patients with
      pulmonary tuberculosis, lung or breast cancer. Indirect immunofluorescence was
      used to determine the count of CD3-, CD4-, CD80, CD38-, CD25-, CD71-, and CD95
      lymphocytes. The levels of thymic peptide antibodies were estimated by enzyme
      immunoassay. Unlike cancer diseases, pulmonary tuberculosis was characterized by
      the combination of a significantly inverse correlation between the relative count
      of CD3-, CD4-, CD8-lymphocytes the levels of thymogen antibodies with a
      significantly direct correlation between the absolute count of CD25- and CD38
      lymphocytes. The studies may recommend that the levels of thymic peptide antigens
      should be determined to select persons with immunodeficiency particularly those
      with inflammatory diseases.

PMID- 15568318
TI  - [Need for psychological correction in patients with pulmonary tuberculosis].
AB  - The paper presents the results of examination using a standardized multifactorial
      personality study schedule in patients with pulmonary tuberculosis, residents in
      the Samara Region, including 123 males and 55 females with first diagnosed
      tuberculosis, 152 males and 101 females with chronic pulmonary tuberculosis.
      Ninety-eight apparently healthy males and 142 females of the same age were
      examined as a control group. The type of a response in the psychotraumatic
      situation and psychological traits were identified. The leading type of a
      response (66%) was hyposthenic (an inhibitory response to stress) in males with
      first identified tuberculosis. Conflict somatization was peculiar to other males,
      as in 46% of the females. The behavioral type of dysadaptation and asocial and
      antisocial responses occur in 38.9% of the males with chronic pulmonary
      tuberculosis and in 25% of the females. 22.2% of the males and 50% of the females
      show a somatic response, which leads to the transition to the psychophysiological
      level, to the occurrence of psychosomatic diseases. Irrespective of the duration
      of the disease, all the patients, both males and females, need psychological
      correction.

PMID- 15568319
TI  - [Use of dissolved ozone in the treatment of experimental tuberculosis in mice].
AB  - Sixty-eight BALB/c mice were infected with the intravenous injections of
      Mycobacterium tuberculosis (MBT), a clinical strain resistant to streptomycin,
      isoniazid, rifampicin, and kanamycin. The mice were divided into 5 groups: Groups
      1 and 2 were control (intact and infected without being treated, respectively).
      Group 3 mice were treated with isoniazid; Group 4 received isoniazid in
      combination with intraperitoneal dissolved ozone (pO3); and Group 5 was given
      pO3. The animals began to die at month 4 of infection. By month 5, mice died all,
      except for intact and pO3-treated ones. On inoculation of MBT from the lung,
      there was a reduction in isoniazid resistance in the pO3-treated groups. The
      lesion was least when isoniazid was used in combination with pO3. The mechanism
      responsible for that pO3 lowers drug resistance in MBT and whether it is
      expedient to co-administer isoniazid and pO3 in undetected drug resistance in MBT
      are under discussion.

PMID- 15568320
TI  - [Role of Chlamydia trachomatis in the clinical picture of pulmonary
      tuberculosis].

PMID- 15568321
TI  - [Rib tuberculosis].

PMID- 15568322
TI  - [History and symbols in tuberculosis control in Russia].

PMID- 15568324
TI  - [Minute of the 235th Meeting of the Thoracic Surgery Section, Surgical Society of
      Moscow and the Moscow region (December 10, 2002)].

PMID- 15568325
TI  - [Proceedings of the Symposium on Topical Problems of Phthisiopulmonology (Moscow,
      March 22, 2004)].

PMID- 15568326
TI  - [Conference of Young Scientists dedicated to the International Day of
      Tuberculosis (March 25, 2004)].

PMID- 15568327
TI  - Air quality in the IVF laboratory: results and survey.

PMID- 15568328
TI  - Significance of increased endometrial thickness in assisted reproduction
      technology treatments.
AB  - PURPOSE: The purpose of this study was to evaluate the relationship between thick
      endometrium and both implantation and pregnancy rates in ART treatments. METHODS:
      The study group was composed of consecutive women undergoing ultrasonographic
      evaluation on the day of hCG administration in our ART unit. Endometrial
      thickness was measured at the thickest part of the midsagittal plane. On the
      basis of the findings, patients were divided into two groups: A--endometrial
      thickness >14 mm (above the 95th percentile) and B--endometrial thickness 7-14 mm
      (between the 5th and 95th percentiles). Patients with a thickness of less than 7
      mm were excluded from the study. RESULTS: In all, 1218 cycles were included in
      the study (50 in Group A and 1168 in Group B). There was no significant
      difference between the groups in mean patient or mean number of embryos
      transferred. Similar pregnancy and implantation rates were noted in Group A (24
      and 11.3%, respectively) and Group B (27.7 and 14.7%, respectively). Endometrial
      thickness was found to have a significant positive correlation with the duration
      of follicular stimulation, and an inverse correlation with woman's age.
      CONCLUSIONS: Increased endometrial thickness (>14 mm) is not associated with
      decreased implantation or pregnancy rates in assisted reproduction.

PMID- 15568329
TI  - Prospective randomized comparison of two embryo culture systems: P1 medium by
      Irvine Scientific and the Cook IVF Medium.
AB  - PURPOSE: To compare the efficacy of two commercially available in vitro
      fertilization (IVF) and embryo culture media systems: the glucose-free P1 Medium
      supplemented with 20% synthetic serum substitute (SSS) (Irvine Scientific), and
      the Cook IVF Medium (Cook, Australia). METHODS: A prospective randomized study.
      Medical center-based IVF Unit affiliated to the Faculty of Medicine of Tel Aviv
      University. IVF patients were randomly assigned to either P1 Medium supplemented
      with 20% SSS (182 patients, 196 cycles) or Cook Medium (167 patients, 179
      cycles). RESULTS: Fertilization rates were similar with both media (52.3 +/- 26.1
      and 53.8 +/- 27.6, respectively). Likewise, no difference was found in
      morphological characteristics and grading of cultured embryos. However, a
      significantly higher proportion of the embryos incubated in the P1 Medium reached
      the four-cell stage on day 2 or the 6-cell stage on day 3 postfertilization,
      compared to those incubated in Cook Medium (54.3% vs. 41.9%, p < 0.0001).
      Clinical pregnancy and delivery rates were improved when oocytes and embryos were
      cultured in P1 Medium. Finally, Implantation rate was significantly higher in the
      P1 Medium Group (9.9% vs. 6%, respectively). CONCLUSIONS: Our results suggest
      that the P1 Medium may be associated with a higher embryo cleavage rate and
      improved implantation rates compared to the Cook IVF Medium.

PMID- 15568330
TI  - Exposure of preimplantation embryos to platelet-activating factor increases birth
      rate.
AB  - PROBLEM: Platelet-activating factor (PAF) plays a significant role in fertility.
      Preimplantation stage embryos produce PAF (ePAF) which is required for
      development. PAF's mechanism of action is receptor-mediated and its presence has
      been reported in the developing mouse and human embryo. Exposure of
      preimplantation stage mouse embryos results in higher implantation rates.
      However, the effect of such treatment on live-birth rates and birth weights has
      not been reported. Therefore, the objective the study was to determine the effect
      of exposing preimplantation mouse embryos to PAF on subsequent birth rate and
      weight. DESIGN: Two-cell stage preimplantation stage mouse embryos exposed to PAF
      (10(-7) M) for 15 min prior to intraoviductal transfer. METHODS: Preimplantation
      stage embryos were recovered from eCG/hCG primed BDF1 female mice. Embryos were
      exposed to synthetic PAF (10(-7) M) for 15 min. PAF-treated embryos were
      transferred to the oviducts of pseudopregnant female CD-1 female mice.
      Superovulated and cultured BDF1 embryos not treated with PAF served as in vitro
      controls and naturally ovulated embryos with no collection/culture served as in
      vivo controls. Embryos were permitted to develop to term (18-21 days). The number
      of pups born per litter and litter weights subsequently were recorded. RESULTS: A
      total of 160 BDF1 mouse embryos were collected, treated, and transferred (20 per
      CD-1 recipient) as described. There was a significant (P < 0.05) increase in the
      number of pups born to the PAF treatment group (56/80; 70%) as compared to the
      control group (44/80; 55%). There was also a significant difference (P < 0.05) in
      litter birth weights between the PAF (1.31 g/litter) and controls groups (1.25
      g/litter). There was a significant difference (P < 0.05) in birth weights between
      the PAF treatment group and the in vivo group (1.51 g/litter). There was a
      significant difference in birth weights between the in vitro-control and in vivo
      groups (1.51 g/litter). There were no observational malformaties to pups born in
      any group. CONCLUSIONS: Brief exposure of preimplantation stage embryos to PAF
      will result in a significant increase of delivery rates (pups/litter) as well as
      birth weights. However, the increase of birth weight was significantly below that
      found naturally. Additional studies are warranted to elucidate the mechanism of
      PAF's action in the preimplantation stage embryo and subsequent uterine
      development.

PMID- 15568331
TI  - In vitro effect of cyclic adenosine 3', 5'-monophosphate (cAMP) on early human
      ovarian follicles.
AB  - PURPOSE: To test the effect of cyclic adenosine 3', 5'-monophosphate (cAMP) on
      early human ovarian follicles during prolonged culture period. METHODS: Donated
      ovarian biopsies from 16 women undergoing gynecological laparoscopy were cut into
      slices and cultured in parallel for 1, 2, or 3 weeks in the presence and the
      absence of 0.5 mM 8-bromo-cAMP. The developmental stages, sizes, and viability of
      the follicles were recorded from histological sections of all samples. RESULTS:
      On day 14, cortical slices cultured with 8-bromo-cAMP showed a significantly
      higher proportion of secondary follicles (50.0% vs. 20.0%) and a lower proportion
      of primordial follicles (9.7% vs. 26.7%) when compared with those cultured
      without 8-bromo-cAMP. On day 21, the proportion of viable follicles in cortical
      slices with 8-bromo-cAMP treatment was significantly higher than that without 8
      bromo-cAMP treatment (79.6% vs. 55.2%). CONCLUSION: CyclicAMP promoted
      folliculogenesis and follicle survival during 14-21 days' culture of human
      ovarian cortical slices.

PMID- 15568332
TI  - Freezing of human immature oocytes using cryoloops with Taxol in the
      vitrification solution.
AB  - PURPOSE: In human frozen immature oocytes, there has been little successful
      delivery. We examined the feasibility of vitrification solution including Taxol,
      cytoskeltal stabilizer. METHODS: We set four experimental groups that immature
      oocytes has cumulus cells or not, or including Taxol or not in the vitrification
      solution. Frozen-thawed oocytes have been performed IVM, ICSI, and IVC. RESULTS:
      There were no significant differences in survival, maturation, and fertilization
      rate, respectively. However, in the group enveloped by cumulus cells and
      including Taxol in the vitrification solution, one embryo was developed to
      blastocyst. CONCLUSIONS: Our results showed that using vitrification solution
      with Taxol proved so effective.

PMID- 15568333
TI  - In vitro fertilization in patients with ovarian endometrioma.
AB  - PURPOSE: To assess the influence of ovarian endometrioma during IVF. METHODS:
      Patients were submitted to cystectomy by the laparoscopic route for exeresis of
      ovarian endometrioma. Group I (n = 28) consisted of patients without ovarian
      endometrioma and group II (n = 14) consisted of patients with recurrence of
      ovarian endometrioma during IVF. RESULTS: Fertilization and cleavage rates were
      higher in group I and the pregnancy rate per transfer was similar in the two
      groups. CONCLUSIONS: The presence of endometrioma during IVF causes a worsening
      of oocyte fertilization and embryo cleavage but does not affect the pregnancy
      rate per transfer.

PMID- 15568334
TI  - Farmers' perceptions, knowledge, and management of coffee pests and diseases and
      their natural enemies in Chiapas, Mexico.
AB  - Small farmers' perceptions of coffee Coffea arabica L. herbivores and their
      natural enemies, how those perceptions relate to field infestation levels, and
      pest management practices being implemented by members from two organic and
      nonorganic coffee grower organizations in the Soconusco region, southeastern
      Mexico, were analyzed through an interview survey, diagnostic workshops, and
      field sampling. The terms pest, disease, and damage were commonly used as
      synonyms. The major phytophagous species, as perceived by the interviewees, were
      Hypothenemus hampei (Ferrari), and to a lesser extent the fungi Corticium
      koleroga Cooke (Hohnel) and Hemileia vastatrix Berkeley & Broome. Among the
      nonorganic farmers, other nonpest-related constraints were regarded as more
      important. Awareness of the existence of natural enemies was low, despite more
      organic farmers have used the ectoparasitoid bethylid Cephalonomia stephanoderis
      Betrem against H. hampei. Labor supplied by household members was most frequent
      for pest control; only organic farmers exchanged labor for this purpose. The
      levels of infestation by H. hampei, Leucoptera coffeella Guerin-Meneville, and C.
      koleroga were lower within the organic coffee stands. However, a low
      effectiveness for pest control was commonly perceived, probably due to a feeling,
      among the organic farmers, of a low impact of their pest management extension
      service, whereas a lack of motivation was prevalent among the nonorganic farmers,
      shown by a concern with their low coffee yields and the emigration of youth. The
      importance of understanding farmers' perceptions and knowledge of pests and their
      natural enemies and the need for participatory pest management approaches, are
      discussed.

PMID- 15568335
TI  - Effect of formic acid formulations on honey bee (Hymenoptera: Apidae) colonies
      and influence of colony and ambient conditions on formic acid concentration in
      the hive.
AB  - The interaction between the effects of varroa, Varroa destructor Anderson &
      Trueman, and formic acid treatments on colonies of honey bees, Apis mellifera L.,
      were examined in two field experiments. In experiment 1, colonies with low varroa
      levels were exposed to two different slow-release formulations and compared with
      untreated colonies. In experiment 2, colonies inoculated with varroa and
      uninoculated colonies were exposed to a slow-release formulation, a pour-on
      formulation, or were left untreated. The effects of treatments, hive temperature,
      and hive relative humidity on formic acid concentration in hive air also were
      examined. Slow-release formic acid application improved colony development in
      colonies that had been inoculated with varroa. However, in uninoculated colonies
      where the mean abundance of varroa was low, slow-release formic acid application
      suppressed colony development. The pour-on application did not have a negative
      impact on worker population growth in uninoculated colonies, but also it was not
      as effective as the slow-release treatment in improving population growth in
      varroa-inoculated colonies. Equivalent volumes of acid applied in pour-on and
      slow-release formulations provided the same cumulative dose in hive air but
      differed in the daily pattern of formic acid release. Colonies that were not
      inoculated with varroa had higher concentrations of formic acid in hive air than
      colonies that were inoculated with varroa on three of the five pour-on
      application dates. The data suggest that reductions in worker population and/or
      activity caused by varroa can interact with ambient conditions to affect the
      volatilization or sorption of formic acid in the hive.

PMID- 15568336
TI  - Formic acid treatment for control of Varroa destructor (Mesostigmata: Varroidae)
      and safety to Apis mellifera (Hymenoptera: Apidae) under southern United States
      conditions.
AB  - The efficacy of a formic acid pad formulation was field tested for control of the
      honey bee parasitic mite Varroa destructor Anderson & Trueman in Florida and
      Texas. This pad formulation gave 39.8 +/- 11.1% control at the end of a 6-wk
      treatment period, which did not significantly differ from the initial sample
      date. Coumaphos treatment provided poor control (38.4 +/- 11.1%) over the 6-wk
      period, confirming reports of coumaphos resistance in the region. Under
      relatively warm winter conditions in southern Texas, formic acid caused mortality
      of developing eggs and brood. If resistance by V. destructor to the two
      acaricides registered for its control in the United States continues, the formic
      acid pad could provide an alternative compound to use as part of an integrated
      pest management approach. Given the low control seen in this trial, however,
      modifications of application technology would seem necessary.

PMID- 15568337
TI  - Compatibility of an organically based insect control program with honey bee
      (Hymenoptera: Apidae) pollination in cantaloupes.
AB  - The application of azadirachtin to foliage of cantaloupes did not significantly
      reduce successful pollination by commercially managed honey bees, Apis mellifera
      L., as measured by numbers of foraging honey bees and yield. Similar results were
      obtained when the synthetic insecticide imidacloprid (used as a standard by
      cantaloupe growers) was applied to the soil. Fruit yield and quality, as a
      function of bee pollination, were statistically equal between the two treatments,
      and equal to that of the untreated control. The standard treatment of
      imidacloprid gave significantly better control than azadirachtin of one pest
      (cucumber beetle) early in the season. Fruit maturity was delayed in untreated
      plots, consistent with light insect pressure observed. These results indicate
      that an organically based insect control approach will not alter bloom acceptance
      and bee forager activity in cantaloupes.

PMID- 15568338
TI  - Field and semifield evaluation of impacts of transgenic canola pollen on survival
      and development of worker honey bees.
AB  - A 2-yr field trial (2001 and 2002) and 1-yr semifield trial (2002) were conducted
      to evaluate the effect of transgenic herbicide (glyphosate) -tolerant canola
      Brassica napus L. pollen on larval and adult honey bee, Apis mellifera L.,
      workers. In the field trial, colonies of honey bees were moved to transgenic or
      nontransgenic canola fields (each at least 40 hectares) during bloom and then
      sampled for larval survival and adult recovery, pupal weight, and hemolymph
      protein concentrations. No differences in larval survival, adult recovery, and
      pupal weight were detected between colonies placed in nontransgenic canola fields
      and those in transgenic canola fields. Colonies placed in the transgenic canola
      fields in the 2002 field experiment showed significantly higher hemolymph protein
      in newly emerged bees compared with those placed in nontransgenic canola field;
      however, this difference was not detected in the 2001 field experiment. In the
      semifield trial, bee larvae were artificially fed with bee-collected transgenic
      and nontransgenic canola pollen and returned to their original colonies. Larval
      survival, pupal survival, pupal weight, and hemolymph protein concentration of
      newly emerged adults were measured. There were no significant differences in any
      of the parameters measured between larvae that were fed transgenic canola pollen
      and those fed nontransgenic corn pollen. Results from this study suggest that
      transgenic canola pollen does not have adverse effects on honey bee development
      and that the use of transgenic canola dose not pose any threat to honey bees.

PMID- 15568339
TI  - Parasitism of obliquebanded leafroller (Lepidoptera: Tortricidae) in commercially
      managed Michigan apple orchards.
AB  - The obliquebanded leafroller, Choristoneura rosaceana (Harris), is one of the
      major arthropod pests of apple in the United States. In 1999 and 2000, a survey
      of the obliquebanded leafroller parasitoid complex in commercially managed apple
      orchards in Michigan's two largest fruit production regions was conducted to
      determine the species present and their importance to obliquebanded leafroller
      population management. In total, 8,961 obliquebanded leafroller larvae were
      collected of which 2,174 were parasitized. Parasitism increased from the
      overwintering generation to the summer generation for both regions and both
      years. In 1999, 11% of the 1,126 overwintering obliquebanded leafrollers
      collected were parasitized, whereas 28% of the 3,669 summer generation were
      parasitized. In 2000, 8% of the 489 overwintering obliquebanded leafrollers
      collected were parasitized, whereas 26% of the 3,677 summer generation
      obliquebanded leafrollers collected were parasitized. In total, 20 species of
      hymenopteran and dipteran parasitoids from seven families were recovered from
      obliquebanded leafroller larvae over the course of the study. The most abundant
      hymenopteran parasitoids were Bassus dimidiator Nees (Braconidae) comprising 48%
      of the total parasitoids, followed by Colpoclypeus florus (Walker) (Eulophidae)
      (8% of the total) and Macrocentrus linearis (Nees) (Braconidae) (2% of the
      total). Dipteran parasitoids (Tachinidae) accounted for 36% of the parasitism and
      were largely comprised of Nilea erecta (Coquillett) (5%) and Actia interrupta
      Curran (13%). These collections represent new host records for B. dimidiator,
      Bassus annulipes (Cresson) Hyphantrophaga blanda (Osten Sacken), and Compsilura
      concinnata (Meigen). The parasitoid C. florus is also reported from Michigan for
      the first time.

PMID- 15568340
TI  - Releases of Psyttalia fletcheri (Hymenoptera: Braconidae) and sterile flies to
      suppress melon fly (Diptera: Tephritidae) in Hawaii.
AB  - Ivy gourd, Coccinia grandis (L.) Voigt, patches throughout Kailua-Kona, Hawaii
      Island, HI, were identified as persistent sources of melon fly, Bactrocera
      cucurbitae (Coquillett). These patches had a low incidence of Psyttalia fletcheri
      (Silvestri), its major braconid parasitoid natural enemy in Hawaii, and were used
      to evaluate augmentative releases of P. fletcheri against melon fly. In field
      cage studies of releases, numbers of melon flies emerging from ivy gourd fruit
      placed inside treatment cages were reduced up to 21-fold, and numbers of
      parasitoids were increased 11-fold. In open field releases of P. fletcheri into
      ivy gourd patches, parasitization rates were increased 4.7 times in release plots
      compared with those in control plots. However, there was no significant reduction
      in emergence of melon flies from fruit. In subsequent cage tests with sterile
      melon flies and P. fletcheri, combinations of sterile flies and P. fletcheri
      produced the greatest reduction (9-fold) in melon fly emergence from zucchini,
      Cucurbita pepo L. Reductions obtained with sterile flies alone or in combination
      with parasitoids were significantly greater than those in the control, whereas
      those for parasitoids alone were not. Although these results suggest that the
      effects of sterile flies were greater than those for parasitoids, from a
      multitactic melon fly management strategy, sterile flies would complement the
      effects of P. fletcheri. Cost and sustainability of these nonchemical approaches
      will be examined further in an ongoing areawide pest management program for melon
      fly in Hawaii.

PMID- 15568341
TI  - Thermal death kinetics of egg and third instar Mediterranean fruit fly (Diptera:
      Tephritidae).
AB  - Two developmental stages of Ceratitis capitata (Wiedemann), 24-h-old eggs and
      third instars, 8 d after oviposition, were subjected to thermal exposures in a
      heating block system, at various temperatures of 46, 48, 50, and 52 degrees C to
      determine the thermal death kinetics of the insects. At these temperatures, 100%
      mortality was achieved by exposure of 300 C. capitata larvae for 60, 15, 4, and 1
      min, respectively. The 0.5 order kinetic model had the best fit to the survival
      ratio for all the treatment temperatures, hence it was used for the prediction of
      the lethal times. The thermal death time (TDT) curves showed that the third
      instars were more heat-resistant than eggs, especially at the two low
      temperatures (46 and 48 degrees C). Under temperature-time combinations that did
      not result in complete kill, the thermal mortality for eggs was also
      significantly higher than that for third instars. The activation energy values
      calculated from the TDT curves were 490.6 and 551.9 kJ/mol, respectively, for
      thermal death of eggs and third instars.

PMID- 15568342
TI  - Medfly (Diptera: Tephritidae) genetic sexing: large-scale field comparison of
      males-only and bisexual sterile fly releases in Guatemala.
AB  - The effect of releases of bisexual (males and female) and unisexual (male only)
      sterilized medflies was compared in three large field evaluations over a 3-yr
      period (1995-1997) in southwestern Guatemala. The two strains tested were a
      genetic sexing strain, Vienna-4/Tol-94, carrying the temperature sensitive tsl
      gene to eliminate females in the egg stage, and the standard bisexual Petapa
      strain. Flies were mass-reared, sterilized by irradiation as pupae, shipped to a
      field center, and released by air as young adults over 2 km by 2 km core areas in
      the centers of separate 6 km by 6 km test plots. Strain performance was monitored
      weekly by trapping sterile and wild male adults in core and buffer areas and by
      collecting eggs from coffee berries to determine induced sterility. Results
      indicated a several-fold advantage for the males-only strain as measured by the
      level of induced sterility, especially at the very high release ratios of 100:1
      recorded in 1997. During that final test year, sterile-fly release rates were
      increased to provide high sterile:wild (S:W) fly ratios in the field, and egg
      sterility reached levels in excess of 70% in plots were the male-only strain was
      used. However, in the plots where the bisexual strain was released, induced
      sterility only reached 12% despite S:W ratios above 1,000:1.

PMID- 15568343
TI  - Recapture of sterile Mediterranean fruit flies (Diptera: Tephritidae) in
      California's Preventative Release Program.
AB  - In southern California, the sterile insect technique has been used since 1994 to
      prevent establishment of the Mediterranean fruit fly, Ceratitis capitata
      (Wiedemann). This method involves the continual mass release of sterile flies,
      which suppress or eliminate any introduced wild fly populations. In addition,
      Jackson traps baited with trimedlure are deployed throughout the preventative
      release region for the dual purpose of detecting wild flies and monitoring
      released sterile flies. Sterile fly recapture data for a 3-yr period was compared
      with climate and to host plant (in which traps were placed). Precipitation was
      negatively correlated; and temperature and relative humidity were positively
      correlated with fly recapture levels. The highest numbers of flies were
      recaptured during trapping periods associated with intermediate relative humidity
      and temperature, and low precipitation. Flies were recaptured throughout the
      entire year, in traps that had been frequently relocated to host plants with
      fruit. This finding suggests that these flies were capable of locating acceptable
      fruit in a variety of abiotic conditions. However, these data do not necessarily
      suggest that measurements unimportant in explaining sterile fly recapture are not
      of value in determining other outcomes important to the goals of sterile release
      programs, such as reducing the likelihood of establishment of an introduced wild
      Mediterranean fruit fly population. Future research might build on these results
      in developing more precise models useful in predicting recapture of sterile
      flies.

PMID- 15568344
TI  - Population dynamics and within-plant distribution of the mite Calacarus
      flagelliseta (Acari: Eriophyidae) on papaya in Hawaii.
AB  - An important element in developing a management strategy for a new pest is the
      study of its seasonal dynamics and within-plant distribution. Here, we studied
      the mite Calacarus flagelliseta Fletchmann, De Moraes & Barbosa on papaya, Papaya
      carica L. (Caricaceae), in Hawaii to quantify 1) patterns of seasonal abundance,
      2) its distribution across different vertical strata of the papaya canopy, and 3)
      shifts in its use of the upper versus the lower surfaces of papaya leaves.
      Nondestructive sampling conducted in two papaya plantings revealed that 1)
      populations of C. flagelliseta peak during the summer; 2) mites are most abundant
      in the middle and lower strata of the plant canopy, and least abundant on the
      youngest leaves found in the upper canopy; and 3) mites are found more
      predominantly on the upper leaf surfaces when overall population density peaks,
      suggesting that individuals move from the lower to the upper leaf surfaces when
      food resources on the lower leaf surface have been exploited by conspecifics.
      These results have significant implications for the development of sampling plans
      for C. flagelliseta in papaya.

PMID- 15568345
TI  - Effect of probiotic adult diets on fitness components of sterile male
      Mediterranean fruit flies (Diptera: Tephritidae) under laboratory and field cage
      conditions.
AB  - The aim of the current study was to investigate the effect of probiotic adult
      diets, i.e., adult diets containing viable symbiotic intestinal bacteria, on the
      pheromone-calling activity, mating success, life expectancy, and survival of mass
      reared male Mediterranean fruit flies, Ceratitis capitata (Wiedemann), as an
      avenue for improving the field performance of sterile males in release programs
      to eradicate, suppress, or prevent spread of wild populations. The effect of
      inoculation of two standard adult diets (sugar-yeast granulate [SY] and sugar
      agar [s]) and two experimental formulations (yeast-reduced granulate [Sy] and
      yeast-enhanced sugar agar [sy]) with Enterobacter agglomerans and Klebsiella
      pneumoniae (typically occurring in the gut of wild flies) on the different
      fitness components was assessed in the laboratory and on field-caged host trees.
      We found that, in the laboratory, males reared on the probiotic yeast-enhanced
      agar, sy, had a significant mating advantage over competitors fed the standard s
      agar (probiotic and control) or noninoculated sy agar; no effect of probiotic
      enrichment (or lowering the yeast content) was found with the granular diets.
      Mating test results obtained in the field were inconsistent with laboratory data
      in that no differences in the numbers of matings were observed between males
      reared on any of the probiotic and control agar diets (or the SY granulate),
      whereas males feeding on the probiotic modified granulate, Sy, scored
      significantly more matings than their control competitors. The pheromone-calling
      activity of males maintained on the granular diets was not affected by probiotic
      enrichment on any of the seven observation days. Agar-fed males, however,
      "called" more frequently on days 6 and 7 (but not on days 1-5) when their diet
      contained the probiotic load. Laboratory survival of granulate-fed males was
      found to be significantly prolonged with probiotic inoculation and lowering the
      yeast content of the standard SY granulate (but not with probiotic inoculation of
      sy). Similarly, males reared on the probiotic and control modified agars (sy)
      survived significantly longer than those feeding on the standard s agars
      (inoculated and control). Again, the results obtained in the field were
      inconsistent, because no differences between treated and control males were found
      for any of the diets. The findings are discussed in the light of other published
      studies on adult nutrition and behavioral ecology in C. capitata.

PMID- 15568346
TI  - Effects of two plant extracts on larval leafminer Liriomyza trifolii (Diptera:
      Agromyzidae) in tomatoes.
AB  - Aqueous extracts from two plants, Urginea maritima L. (Liliaceae) and Euphorbia
      myrsinites L. (Euphorbiaceae), were tested for their insecticidal activity
      against the leafminer Liriomyza trifolii (Burgess) on infested tomato,
      Lycopersicon esculentum Mill., plants in the laboratory and field. Two grams of
      plant material was extracted with 100 ml of water and then diluted 1:100, 1:50,
      and 1:25 with distilled water. Diluted plant extract was either applied to the
      infested tomato leaves or by soil drench and was compared with foliar application
      of cyromazine. All dilutions of both plant extracts caused significant control of
      the leafminer larvae and maintained populations below those of the nontreated
      control plants in all trials. Only at the most concentrated dilutions (1:25) were
      the plant extracts statistically similar to the cyromazine treatment.
      Furthermore, greenhouse yields from all of the foliar treatments were
      statistically similar to the cyromazine treatment and significantly better than
      the nontreated control. Four species of leafminer parasitoids were found in the
      greenhouse; however, the percentage of parasitism was significantly less in all
      treated replicates than in the nontreated control replicates. Aqueous extracts
      from these two plant extracts exhibited both translaminar and systemic activity
      and are potential candidates as new organic insecticides.

PMID- 15568347
TI  - Effects of neonicotinoid insecticides on the bionomics of twospotted spider mite
      (Acari: Tetranychidae).
AB  - Previous reports indicate that applications of imidacloprid, a neonicotinoid
      insecticide, can lead to population buildups of twospotted spider mite,
      Tetranychus urticae Koch, in the field. Moreover, laboratory studies showed
      enhanced fecundity of T. urticae after an imidacloprid treatment. In this study,
      experiments were conducted in the greenhouse to investigate the potential effects
      of imidacloprid and several other neonicotinoid insecticides on fecundity, egg
      viability, preimaginal survivorship, and sex ratio of T. urticae (German strain
      WI) on French beans, Phaseolus vulgaris L. Four insecticides, i.e., imidacloprid
      (Confidor 200SL), thiacloprid (Calypso 480 SC), acetamiprid (Mospilan 70 WP), and
      thiamethoxam (Actara 25 WG), were tested at field-relevant (100, 120, 125, and 95
      ppm) and sublethal doses (10, 12, 12.5, and 9.5 ppm), respectively. Both spray
      and drench applications were tested. At field-relevant doses, fecundity of T.
      urticae decreased and was lower in the treatments compared with the untreated
      control, whereas preimaginal survivorship and proportion of female offspring
      (i.e., sex ratio) were lower compared with the control. At sublethal doses, no
      significant differences were found among the treatments. Data on egg viability,
      preimaginal survivorship, and sex ratio at sublethal doses followed the same
      trends as at field-relevant doses. In an additional experiment, the metabolism of
      imidacloprid into monohydroxy-imidacloprid, olefine, guanidine, and 6
      chloronicotinic acid was compared with the oviposition pattern of T. urticae.
      These findings are discussed with regard to previous laboratory and field
      observations of imidacloprid-induced fertility increases in T. urticae.

PMID- 15568348
TI  - Effect of temperature on efficacy of insecticides to differential grasshopper
      (Orthoptera: Acrididae).
AB  - The effect of temperature on activity of insecticides for controlling
      grasshoppers in leafy green vegetables was evaluated. Insecticides evaluated had
      differing modes of action and included diflubenzuron, azadirachtin, Beauveria
      bassiana, spinosad, endosulfan, esfenvalerate, and naled. We evaluated these
      insecticides for efficacy to third instars of differential grasshopper,
      Melanoplus differentialis (Thomas), at temperatures ranging from 10 to 35 degrees
      C. In the laboratory, treatment with esfenvalerate resulted in 100% mortality at
      temperatures of 10 to 35 degrees C, and efficacy was not temperature dependent.
      Treatment with spinosad resulted in similar mortality as with esfenvalerate at
      all temperatures except 10 degrees C. The activity of B. bassiana was greatest at
      25 degrees C and was adversely affected by high and low temperatures. Treatment
      with diflubenzuron resulted in increased mortality at high temperatures, and at
      35 degrees C its activity was similar to that of esfenvalerate and spinosad. The
      activity of azadirachtin ranged from 19 to 31% and was not influenced by
      temperature. In field studies, spinosad, diflubenzuron, and esfenvalerate
      provided differing levels of mortality both at application and when nymphs were
      exposed to 1-h-old residues. However, only spinosad and diflubenzuron provided
      similar levels of mortality when nymphs were exposed to 24-h-old residues. The
      residual activity of endosulfan, naled, esfenvalerate, and spinosad decreased
      with increasing time (0-24 h) after exposure to sunlight and high summer
      temperatures. Compared with other insecticides, naled had a short residual
      activity period and activity was dependent upon immediate contact with the nymphs
      or their substrate. B. bassiana was inactive under high temperatures and intense
      sunlight as occurs in summer.

PMID- 15568349
TI  - Plant-incorporated Bacillus thuringiensis resistance for control of fall armyworm
      and corn earworm (Lepidoptera: Noctuidae) in corn.
AB  - Fall armyworm, Spodoptera frugiperda (J.E. Smith), and corn earworm, Helicoverpa
      zea (Boddie), perennially cause leaf and ear damage to corn, Zea mays L., in the
      southeastern United States. Transgenic Bacillus thuringiensis (Bt) hybrids with
      the Bt11, MON810, or 176 events expressing the Cry1Ab insecticidal endotoxin from
      were evaluated for control fall armyworm and corn earworm at seven locations in
      Georgia during 1999 and 2000. Corn was planted at the recommended time for each
      location and 1 and 2 mo later in the southern locations. All Bt events
      consistently reduced whorl infestation and damage, although event 176 did not
      prevent whorl damage in the later plantings in the southern locations in both
      years. All events also reduced seedling damage by the lesser cornstalk borer,
      Elasmopalpus lignosellus (Zeller), in one trial and stalk infestations and tunnel
      length by southwestern corn borers, Diatraea grandiosella Dyar, in another trial.
      Hybrids containing Bt11 and MON810 events reduced ear infestations in all trials,
      although reductions were small in later plantings. Nevertheless, both events
      reduced grain damage from earworms and armyworms by an average +/- SE of 52.5 +/-
      5.1% in all trials. The hybrid containing event 176 did not reduce ear
      infestations and damage. Total grain aflatoxin concentrations were not
      significantly affected by Bt resistance in any trial (N = 17). Yield responses
      were variable with the prevention of yield loss being proportional to the
      severity of insect damage. Although plantings made after the recommended time did
      not consistently benefit from Bt resistance, Bt11 and MON810 events were
      effective in reducing damage to field corn when large infestations occurred. The
      Bt11 and MON810 events mitigated the risk of severe lepidopteran damage to corn,
      thereby making later plantings of corn feasible in double-cropping systems.

PMID- 15568350
TI  - Boll weevil (Coleoptera: Curculionidae) survival through cotton gin trash fans.
AB  - There is concern that cotton gins may serve as loci for reintroduction of boll
      weevils, Anthonomus grandis grandis Boheman, to eradicated or suppressed zones
      when processing weevil-infested cotton from neighboring zones. Previous work has
      shown that virtually all weevils entering the gin in the seed cotton will be
      removed before they reach the gin stand. Those not killed by the seed cotton
      cleaning machinery will be shunted alive into the trash fraction, which passes
      through a centrifugal trash fan before exiting the gin. The objective of this
      study was to determine survival potential of boll weevils passed through a trash
      fan. Marked adult weevils were distributed in gin trash and fed through a 82.6-cm
      (32.5-in.) diameter centrifugal fan operated across a range of fan-tip speeds. A
      small number of boll weevils were recovered alive immediately after passage
      through the fan, but all were severely injured and did not survive 24 h. In
      another experiment, green bolls infested with both adult- and larval-stage
      weevils were fed through the fan. Several teneral adults survived 24 h, and there
      was no evidence that fan-tip speed affected either initial survival of weevils,
      or the number of unbroken boll locks that could harbor an infesting weevil. Thus,
      designating a minimum fan-tip speed for ensuring complete kill is not possible
      for the boll weevil. Experiments suggest that a device installed in a gin that
      partially crushes or cracks bolls open before entering a trash fan will increase
      mortality, possibly enough that further precautions would be unnecessary.

PMID- 15568351
TI  - Effect of attract and kill formulations and application rates on trap catches of
      European pine shoot moth (Lepidoptera: Tortricidae) and shoot damage in Scots
      pine saplings.
AB  - Attract and kill technology was tested for management of European pine shoot
      moth, Rhyacionia buoliana (Denis & Schiffermuller), in 4-6-yr-old Scots pine,
      Pinus sylvestris L., plantations managed by Jablonna and Pultusk Forest
      Districts, Poland. In 2001, two formulations based on ricinoleic acid and
      hydrocarbon fraction (petroleum jelly) in combination with (E)-9-dodecenyl
      acetate, the sex pheromone of the pine shoot moth; permethrin as a contact
      insecticide; and Tinuvin UV absorber were used. In 2002, different formulations
      and application rates of the attracticide based on petroleum jelly were tested.
      Significantly reduced trap catches occurred in plots treated with three
      attracticide formulations [Rhykil-1 (with Tinuvin UV absorber), Rhykil-2 (with a
      new UV absorber, 3,3'-dihydroxy-2,2'-bipyridyl), and Rhykil-3 (without the
      insecticide)] at 3,000 droplets per hectare in comparison with those in control
      plots, suggesting that all formulations were highly effective. Significantly
      lower catches than in control plots also were observed when Rhykil-1 was applied
      at 1000, 2,000, and 3,000 droplets per hectare. However, only slight reduction of
      shoot damage in treated plots was observed in both experiments. The formulation
      without the insecticide had similar efficacy to that of the formulation combined
      with the insecticide. In 2003, the Rhykil-2 attracticide was tested at 250, 500,
      and 1000 droplets per hectare. Although there were no significant differences in
      trap catches between treated and control plots, shoot damage level was reduced
      substantially in all treated plots. These results suggest that attract and kill
      technology may be used at rates lower than 1000 droplets per hectare for
      management of R. buoliana; however, its "kill" effect should be confirmed in
      further studies.

PMID- 15568352
TI  - Bacillus thuringiensis subsp. kurstaki aerial spray prescriptions for balsam fir
      stand protection against spruce budworm (Lepidoptera: Tortricidae).
AB  - Although commercial formulations of Bacillus thuringiensis subsp. kurstaki (Btk)
      are being widely used in forest protection against lepidopteran defoliators,
      optimal application prescriptions have often yet to be worked out in detail. We
      conducted field experiments over a 6-yr period (1996-2001) in southwestern Quebec
      to determine application prescriptions for optimal protection of balsam fir,
      Abies balsamea (L.), healthy stands against the spruce budworm, Choristoneura
      fumiferana (Clemens) (Lepidoptera: Tortricidae). At moderate larval densities
      (<30 larvae per 45-cm branch tip), similar foliage protection was achieved with
      one or two Btk applications of 30 billion international units per hectare
      (BIU/ha). When larval densities exceeded 30 larvae per branch tip, two successive
      applications of 30 BIU/ha significantly increased foliage protection. Whether the
      second application took place 5 or 10 d after the first spray did not affect
      treatment efficacy. Increasing the application dosage from 30 to 50 BIU/ha did
      not lead to better foliage protection against high larval densities, but the
      current standard dosage of 30 BIU/ha saved more foliage than 15 BIU/ha against
      moderate populations. The recommended dosage of 30 BIU can be applied in lower
      application volumes (1.5 liters/ha) by using a high-potency product (20
      BIU/liter), because we did not observe a reduction in efficacy compared with the
      application of a lower potency product (12.7 BIU/liter) in 2.37 liters/ha. We
      also demonstrated that Btk can be applied much earlier in the season without
      compromising spray efficacy: there was no difference in treatment efficacy of
      double applications at 30 BIU/ha when the first spray was timed for early third,
      peak third, or early fourth instars.

PMID- 15568353
TI  - Feeding preference of three lady beetle predators of the hemlock woolly adelgid
      (Homoptera: Adelgidae).
AB  - In a laboratory study, we tested the feeding preferences of three coccinellid
      predators of hemlock woolly adelgid, Adelges tsugae Annand, an introduced pest of
      hemlock in the eastern United States. The species tested were Sasajiscymnus
      tsugae Sasaji & McClure (formerly Pseudoscymnus tsugae) from Japan, Scymnus
      ningshanensis Yu & Yao from China, and Harmonia axyridis (Pallas), a generalist
      species introduced from Asia that is currently widespread in eastern hemlock,
      Tsuga canadensis Carriere, forests. We measured the feeding preference of each
      beetle species when given the choice of A. tsugae and either 1) Pineus strobi
      (Hartig) on Pinus strobus L.; 2) Adelges laricis Vallot on Larix decidua Mill.;
      3) Adelges cooleyi (Gillette) on Pseudotsuga menziesii (Mirb.) Franco; or 3)
      Paraprociphilus tessellatus (Fitch) on Alnus serrulata (Ait.) Willd. We evaluated
      beetle preference for adults, nymphs, and eggs of each prey species. Generally,
      when adult or nymphal prey stages were compared, S. tsugae preferred A. tsugae
      adults to P. strobi, A. cooleyi, A. laricis, and P. tessellatus. S. ningshanensis
      showed less preference between adelgid species, but it did not prefer P.
      tessellatus nymphs. When preferences for adelgid eggs were assayed, S. tsugae and
      S. ningshanensis showed no preference between A. tsugae and A. cooleyi or P.
      strobi, but S. tsugae did prefer A. tsugae to A. laricis. Larvae of S. tsugae
      were unable to survive on P. tessellatus nymphs. H. axyridis adults readily
      consumed both A. tsugae and P. tessellatus, but H. axyridis larvae did not
      complete their life cycle on A. tsugae. Our host range tests suggest that S.
      ningshanensis and S. tsugae may feed on several species of Adelgidae and that A.
      tsugae is often preferred.

PMID- 15568354
TI  - Yield reduction in Brassica napus, B. rapa, B. juncea, and Sinapis alba caused by
      flea beetle (Phyllotreta cruciferae (Goeze) (Coleoptera: Chrysomelidae))
      infestation in northern Idaho.
AB  - Phyllotreta cruciferae is an important insect pest of spring-planted Brassica
      crops, especially during the seedling stage. To determine the effect of early
      season P. cruciferae infestation on seed yield, 10 genotypes from each of two
      canola species (Brassica napus L. and Brassica rapa L.) and two mustard species
      (Brassica juncea L. and Sinapis alba L.) were grown in 2 yr under three different
      P. cruciferae treatments: (1) no insecticide control; (2) foliar applications of
      endosulfan; and (3) carbofuran with seed at planting plus foliar application of
      carbaryl. Averaged over 10 genotypes, B. rapa showed most visible P. cruciferae
      injury and showed greatest yield reduction without insecticide application.
      Mustard species (S. alba and B. juncea) showed least visible injury and higher
      yield without insecticide compared with canola species (B. napus and B. rapa).
      Indeed, average seed yield of S. alba without insecticide was higher than either
      B. napus or B. rapa with most effective P. cruciferae control. Significant
      variation occurred within each species. A number of lines from B. napus, B.
      juncea, anid S. alba showed less feeding injury and yield reduction as a result
      of P. cruciferae infestation compared with other lines from the same species
      examined, thus having potential genetic background for developing resistant
      cultivars.

PMID- 15568355
TI  - Tactics for management of thrips (Thysanoptera: Thripidae) and tomato spotted
      wilt virus in tomato.
AB  - Four studies were conducted in Georgia during spring 1999, 2000, 2001, and 2002
      to evaluate various management tactics for reducing thrips and thrips-vectored
      tomato spotted wilt virus (TSWV) in tomato and their interactions relative to
      fruit yield. Populations of thrips vectors of TSWV, Frankliniella occidentalis
      (Pergande) and Frankliniella fusca (Hinds), were determined using flower and
      sticky trap samples. The management practices evaluated were host plant
      resistance, insecticide treatments, and silver or metallic reflective mulch.
      Averaged over all tests, the TSWV-resistant tomato 'BHN444' on silver mulch
      treatment had the largest effect in terms of reducing thrips and spotted wilt and
      increasing marketable yield. Of the insecticide treatments tested, the
      imidacloprid soil treatment followed by early applications of a thrips-effective
      foliar insecticide treatment provided significant increase in yield over other
      treatments. Tomato yield was negatively correlated with the number of F. fusca
      and percentage of TSWV incidence. F. occidentalis per blossom was positively
      correlated with percentage of TSWV incidence, but not with yield. No significant
      interactions were observed between cultivar reflective mulch main plot treatments
      and insecticide subplot treatments; thus, treatment seemed to be additive in
      reducing the economic impact of thrips-vectored TSWV. Control tactics that manage
      thrips early in the growing season significantly increased tomato yield in years
      when the incidence of TSWV was high (>17%).

PMID- 15568356
TI  - Effects of aging and dilution on attraction and toxicity of GF-120 fruit fly bait
      spray for melon fly control in Hawaii.
AB  - Attractiveness and toxicity of GF-120 Fruit Fly Bait (Dow AgroScience
      Indianapolis, IN) to melon flies, Bactrocera cucurbitae Coquillett, were examined
      to assess the effects of concentration and aging. We tested dilutions of 20, 40,
      and 80 ppm (AI) (spinosad) against water controls. The 80 and 40 ppm treatments
      were significantly more attractive than the 20 ppm and control treatments.
      Attraction was compared between baits aged for 2 and 24 h, fresh bait and water
      controls. Age had significant effects on both attractiveness and toxicity of GF
      120. Baits aged for 2 h were 11 times less attractive to female melon flies than
      fresh bait. Mortality rates were reduced by 50% when GF-120 was subjected to
      rain. Our results suggest the need for frequent applications of GF-120 to obtain
      maximum benefits, particularly in wet tropical climates.

PMID- 15568357
TI  - Comparison of sticky wing and cone pheromone traps for monitoring seasonal
      abundance of black cutworm adults and larvae on golf courses.
AB  - Black cutworm, Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae), flight
      activity was monitored on three golf courses in Wisconsin by using two types of
      pheromone traps: the Texas cone trap and sticky wing trap. The Texas cone trap
      caught significantly more black cutworm males compared with the sticky wing trap,
      capturing almost 12-fold more males. Black cutworm males were most abundant
      during mid-July in 2001 and 2002, between 700 and 800 cumulative degree-days.
      Flight activity also was detected in early May and mid-August, but these peaks
      were not as pronounced as in mid-July. No definitive relationship between black
      cutworm flight activity and subsequent larval infestations on golf course putting
      greens occurred.

PMID- 15568358
TI  - Evaluation of a nonconventional insecticide and appropriate application timing
      for destruction of gypsy moth (Lepidoptera: Lymantriidae) egg masses.
AB  - Two field studies were conducted in 2001-2002 and 2003 to evaluate the
      effectiveness and appropriate application timing of Golden Pest Spray Oil (GPSO)
      for destruction of gypsy moth, Lymantria dispar (L.) (Lepidoptera: Lymantriidae),
      egg masses in Wisconsin. GPSO is a commercially available, registered pesticide
      that is predominantly comprised of a soybean-oil base (93%); its primary mode of
      action is by means of suffocation. Because gypsy moth spends the majority (>75%)
      of its life cycle in the egg stage (August-April), the potential utility of this
      product by arborists, city foresters, landscapers, and homeowners is high,
      especially because GPSO is a United States Environmental Protection Agency
      registered, nonconventional pesticide that is considered relatively nontoxic.
      When GPSO was applied at a 1:1 ratio with water, >96% control of gypsy moth egg
      masses was achieved, regardless of application timing (October, 3 d before egg
      hatch).

PMID- 15568359
TI  - Effect of horizontal transfer of barrier insecticides to control Argentine ants
      (Hymenoptera: Formicidae).
AB  - Horizontal transfer of three contact insecticides, bifenthrin, beta-cyfluthrin,
      and fipronil, was tested in laboratory colonies. Donor ants were exposed for 1
      min to insecticide-treated sand substrates and placed with unexposed ant colonies
      at two different temperatures. Mortality was monitored to compare the ability of
      donors to transfer lethal doses of these insecticides to untreated individuals.
      Treated donor insects, live or dead, were added into colonies to determine the
      importance of donor behavior on lethal transfer. Fipronil was readily
      transferable between individuals, resulting in high mortality rates. Bifenthrin
      and beta-cyfluthrin were less transferable, exhibiting moderate-to-low mortality
      rates similar to the controls. Greater mortality occurred at 27-29 degrees C than
      at 21-23 degrees C for bifenthrin, but not the other treatments or controls.
      Colony mortality did not significantly increase when adding live donors,
      suggesting that necrophoresis was probably an important donor behavior in
      addition to grooming and trophallaxis on horizontal transfer.

PMID- 15568360
TI  - Resistance and synergistic effects of insecticides in Bactrocera dorsalis
      (Diptera: Tephritidae) in Taiwan.
AB  - Oriental fruit flies, Bactrocera dorsalis (Hendel), were treated with 10
      insecticides, including six organophosphates (naled, trichlorfon, fenitrothion,
      fenthion, formothion, and malathion), one carbamate (methomyl), and three
      pyrethroids (cyfluthrin, cypermethrin, and fenvalerate), by a topical application
      assay under laboratory conditions. Subparental lines of each generation treated
      with the same insecticide were selected for 30 generations and were designated as
      x-r lines (x, insecticide; r, resistant). The parent colony was maintained as the
      susceptible colony. The line treated with naled exhibited the lowest increase in
      resistance (4.7-fold), whereas the line treated with formothion exhibited the
      highest increase in resistance (up to 594-fold) compared with the susceptible
      colony. Synergism bioassays also were carried out. Based on this, S,S,S-tributyl
      phosphorotrithioate displayed a synergistic effect for naled, trichlorfon, and
      malathion resistance, whereas piperonyl butoxide displayed a synergistic effect
      for pyrethroid resistance. All 10 resistant lines also exhibited some cross
      resistance to other insecticides, not only to the same chemical class of
      insecticides but also to other classes. However, none of the organophosphate
      resistant or the methomyl-resistant lines exhibited cross-resistance to two of
      the pyrethroids (cypermethrin and fenvalerate). Overall, the laboratory
      resistance and cross-resistance data developed here should provide useful tools
      and information for designing an insecticide management strategy for controlling
      this fruit fly in the field.

PMID- 15568361
TI  - Seasonal changes of methamidophos susceptibility and biochemical properties in
      Plutella xylostella (Lepidoptera: Yponomeutidae) and its parasitoid Cotesia
      plutellae (Hymenoptera: Braconidae).
AB  - Methamidophos resistance and acetylcholinesterase (AChE) insensitivity to
      methamidophos, dichlorvos, and carbofuran were determined in the field
      populations of Plutella xylostella (L.) (Lepidoptera: Yponomeutidae) and its
      parasitoid Cotesia plutellae Kurdjumov (Hymenoptera: Braconidae) collected from
      the corresponding hosts between October 1998 and December 2003 in Fuzhou and
      Minhou, Fijian, China. Resistance levels to methamidophos and AChE insensitivity
      to the three insecticides in the two species of insects were high during autumn
      and spring and low during summer. Resistance to methamidophos was 15.3- and 12.6
      fold higher in resistant F0 parents of P. xylostella and C. plutellae than in
      their susceptible F11 progeny, respectively. The bimolecular rate constant (k(i))
      values of AChE to methamidophos, dichlorvos, and carbofuran were 4.6-, 6.3-, and
      7.7-fold higher in F11 progeny of P. xylostella, and 3.7-, 4.5-, and 3.7-fold
      higher in F11 progeny of C. plutellae than those in their F0 parents,
      respectively. Compared with susceptible F11 progeny, the resistance ratios for
      methamidophos were 4.2-29.8 and 3.8-13.1 in 21 field populations of P. xylostella
      and C. plutellae, respectively. The k(i) values of AChE to methamidophos,
      dichlorvos, and carbofuran were 2.0-21.6-, 3.6-9.5-, and 2.6-9.2-fold higher in
      F11 progeny of P. xylostella, and 1.8-7.6-, 1.9-4.6-, and 2.2-7.6-fold higher in
      F11 progeny of C. plutellae than those in 21 field populations, respectively.
      Significant correlative variations of methamidophos resistance as well as
      significant correlative variations of k(i) values of AChE to insecticides between
      the two species of insects also were found in space and time. The k(i) values of
      AChE to insecticides in C. plutellae were far higher than those in P. xylostella.
      There were no obvious differences in the Km and Vmax of AChE between F0 parents
      and F11 progeny of P. xylostella and C. plutellae, respectively. But
      carboxylesterase activity was 1.6-fold higher in F0 parents of C. plutellae than
      in F11 progeny, and glutathione S-transferase activity was 1.5-fold higher in F0
      parents of P. xylostella than in F11 progeny. The results suggested that the AChE
      insensitivity to insecticides might play the most important role in methamidophos
      resistance in the two species of insects. From these results, a spatial and
      temporal correlative evolution of methamidophos resistance and insensitive AChE
      was found to exist between P. xylostella and C. plutellae.

PMID- 15568362
TI  - Relative fitness of Cry1A-resistant and -susceptible Helicoverpa armigera
      (Lepidoptera: Noctuidae) on conventional and transgenic cotton.
AB  - Glasshouse and laboratory experiments were conducted to evaluate the relative
      fitness of Cry1A-susceptible and laboratory-selected resistant strains of
      Helicoverpa armigera (Hubner). Life history parameters of H. armigera larvae
      feeding on young cotton plants showed a significant developmental delay of up to
      7 d for the resistant strain compared with the susceptible strain on non-Bacillus
      thuringiensis (Bt) cotton. This fitness cost was not evident on artificial diet.
      There was no developmental delay in the F1 hybrid progeny from the reciprocal
      backcross of the resistant and susceptible strains, indicating that the fitness
      cost is recessive. In two cohorts tested, survival to pupation of resistant
      larvae on Bt cotton expressing Cry1Ac was 54 and 51% lower than on non-Bt cotton,
      whereas all susceptible and F1 larvae tested on Cry1Ac cotton were killed.
      Mortality of susceptible larvae occurred in the first or second instar, whereas
      the F1 larvae were able to develop to later instars before dying, demonstrating
      that resistance is incompletely recessive. The intrinsic rate of increase was
      reduced by >50% in the resistant strain on Cry1Ac cotton compared with the
      susceptible strain on non-Bt cotton. There was a significant reduction in the
      survival of postdiapausal adults from the resistant strain and the F1 strains,
      indicating that there is a nonrecessive overwintering cost associated with Cry1A
      resistance in H. armigera.

PMID- 15568363
TI  - Effects of gossypol on fitness costs associated with resistance to Bt cotton in
      pink bollworm.
AB  - Fitness costs associated with insect resistance to Bacillus thuringiensis (Bt)
      crops may help to delay or prevent the spread of resistance alleles, especially
      when refuges of non-Bt host plants are present. The potential for such delays
      increases as the magnitude and dominance of fitness costs increase. Here, we
      examined the idea that plant secondary chemicals affect expression of fitness
      costs associated with resistance to Bt cotton in Pectinophora gossypiella
      (Saunders). Specifically, we tested the hypotheses that gossypol affects the
      magnitude or dominance of fitness costs, by measuring performance of three
      independent sets of pink bollworm populations fed artificial diet with and
      without gossypol. Each set had an unselected susceptible population, a resistant
      population derived by selection from the susceptible population, and the F1
      progeny of the susceptible and resistant populations. No individuals completed
      development on diets with gossypol in one set, suggesting that these individuals
      partially lost the ability to detoxify this chemical. In the other two sets,
      costs affecting survival did not support the hypotheses, but costs affecting
      pupal weight did. Adding gossypol to diet increased the magnitude and dominance
      of costs affecting pupal weight. In one of the two sets with survivors on diet
      with gossypol, costs affecting development time were less recessive when gossypol
      was present in diet. These results indicate that gossypol increased the magnitude
      and dominance of some fitness costs. Better understanding of the effects of
      natural plant defenses on fitness costs could improve our ability to design
      refuges for managing insect resistance to Bt crops.

PMID- 15568364
TI  - Comparative production of Helicoverpa zea (Lepidoptera: Noctuidae) from
      transgenic cotton expressing either one or two Bacillus thuringiensis proteins
      with and without insecticide oversprays.
AB  - Transgenic cotton, Gossypium hirsutum (L.), expressing either one or two Bacillus
      thuringiensis ssp. kurstaki Berliner (Bt) proteins was compared with the
      conventional sister line in field experiments with regard to production of
      bollworm, Helicoverpa zea (Boddie), and bolls damaged by bollworm. The relative
      numbers of bollworms that developed on Bollgard (Monsanto Co., St. Louis, MO),
      Bollgard II (Monsanto Co.), and conventional cotton were estimated under
      nontreated conditions in 2000 and both insecticide-treated and nontreated
      conditions in 2001-2002 in North Carolina tests. Averaged across seven field
      studies under nontreated conditions, Bollgard cotton generated statistically
      similar numbers of large (L4-L5) bollworm larvae compared with the conventional
      variety; however, Bollgard cotton produced significantly fewer damaged bolls and
      bollworm adults than the conventional variety. Production of large larvae,
      damaged bolls, and adults was decreased dramatically by Bollgard II cotton as
      compared with Bollgard and conventional varieties. When comparing insecticide
      treated and nontreated cotton genotypes, both Bt cotton sustained less boll
      damage than the conventional variety averaged across insecticide regimes;
      furthermore, Bollgard II cotton had fewer damaged bolls than the Bollgard
      variety. When averaged across cotton genotypes, pyrethroid oversprays reduced the
      numbers of damaged bolls compared with the nontreated cotton. Insecticide-treated
      Bollgard cotton, along with insecticide-treated and nontreated Bollgard II cotton
      reduced production of bollworm larvae, pupae, and adults. However, the addition
      of pyrethroid oversprays to Bollgard II cotton seemed to be the best resistance
      management strategy available for bollworm because no bollworms were capable of
      completing development under these conditions.

PMID- 15568365
TI  - Monitoring western corn rootworm (Coleoptera: Chrysomelidae) susceptibility to
      carbaryl and cucurbitacin baits in the areawide management pilot program.
AB  - Areawide pest management involves the uniform application of a pest control
      strategy over wide geographic areas. Therefore, these programs are likely to
      impose intense selective pressures, and the risk for resistance development among
      pest species for which areawide management programs are implemented is likely to
      be high. Pilot studies for areawide management of western corn rootworm,
      Diabrotica virgifera virgifera LeConte, were conducted from 1996 to 2002 at four
      different sites across the Corn Belt. This program used cucurbitacin baits to
      deliver high doses of a traditional neurotoxic insecticide (carbaryl) to
      individual insects while reducing the overall rate of insecticide use. Because of
      the concern and potential for resistance evolution, annual assessments of
      susceptibility to the active ingredient carbaryl were conducted both within the
      managed area as well as from untreated control areas. Significantly reduced
      susceptibility to carbaryl based on survival at a diagnostic concentration was
      detected in three of the four management sites (Kansas, Iowa, and
      Illinois/Indiana), whereas susceptibility of beetles collected outside the
      managed areas remained unchanged. Additionally, significantly reduced
      responsiveness to cucurbitacin baits was observed in beetles collected from the
      managed area relative to the control area at the same three sites. These results
      suggest strongly that areawide management has the potential to select for
      resistance and that a strategy for managing resistance and reducing selective
      pressure should be proactively implemented.

PMID- 15568366
TI  - Susceptibility of two different strains of Aedes aegypti (Diptera: Culicidae) to
      plant oils.
AB  - The toxicity of 11 oils extracted from plants commonly grown in the Himalayan
      region was studied using larvae of two Aedes aegypti (L.) strains. A strain from
      Liverpool, England, was highly susceptible to these oils. The LC50 values were
      much higher in a local laboratory strain. Daucus carota L. oil was highly toxic
      in both strains. Differences in the susceptibility of these strains to the action
      of the test oils and their potential use in integrated pest management are
      discussed.

PMID- 15568367
TI  - Relative concentration of Cry1A in maize leaves and cotton bolls with diverse
      chlorophyll content and corresponding larval development of fall armyworm
      (Lepidoptera: Noctuidae) and southwestern corn borer (Lepidoptera: Crambidae) on
      maize whorl leaf profiles.
AB  - To manage insect resistance to transgenic crops that express insecticidal
      proteins from Bacillus thuringiensis (Bt) Berliner, the U.S. Environmental
      Protection Agency recommends a refuge-based insect resistance management strategy
      where a percentage of non-Bt (refuge) crop is grown in proximity to a Bt
      expressing crop. An important requirement for this strategy is that the toxin
      exists at a high effective dose for control of the target pest(s), so that
      heterozygous individuals in the population do not reach adulthood. Factors that
      cause reduced levels of toxin in the plant are a threat to this strategy. We
      quantified Cry1Ab from different areas of the maize, Zea mays L., leaf. In
      general, the distal tip of the V7 maize leaf had a higher concentration of Cry1Ab
      compared with the middle section of the V7 leaf, and the middle section of the
      developing V9 leaf had the lowest concentration of Cry1Ab. When these sections of
      maize tissue were fed to fall armyworm, Spodoptera frugiperda (J.E. Smith), and
      southwestern corn borer, Diatraea grandiosella Dyar, there was not a reduction in
      development or an increase in mortality with tissue that had higher
      concentrations of toxin. Another study tested the relative concentration of
      Cry1Ab between the white-yellow, yellow-green, and green portions of the
      developing ninth leaf within the maize whorl. There were differences in Cry1Ab
      concentration among these leaf areas. The green tissue had the highest
      concentration of toxin followed by the yellow-green and white-yellow tissues.
      Correlations between concentration of Cry1Ab and 5-d fall armyworm larval weights
      among the three leaf color profiles were all significant and negative, i.e.,
      decreased concentration of Cry1Ab in the leaf tissue resulted in increased 5-d
      larval weights. There was 100% mortality to the southwestern corn borer larvae
      fed Cry1Ab maize leaf tissue. Differences in the amount of Cry1Ab in the
      developing V9 leaf profiles did not alter the absolute susceptibility of the
      southwestern corn borer to the toxin. In cotton, Gossypium hirsutum L., the
      amount of Cry1Ac was significantly lower in boll tips where flowers had remained
      attached compared with normal boll tips. Boll tips where the flowers remained
      attached are often the site where corn earworms, Helicoverpa zea (Boddie),
      penetrate Bt cotton bolls. This study demonstrated that, in two diverse plant
      species, tissue that has low chlorophyll content does not fully express Cry1A.
      Photosynthesis regulating factors related to mRNA transcription and translation
      should be studied for their effect on Cry1A production and insect control.

PMID- 15568368
TI  - Effect of environment on resistance to the European corn borer (Lepidoptera:
      Crambidae) in maize.
AB  - The European corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae), is
      a major pest of maize, Zea mays L., in many temperate parts of the world.
      Genotype-by-environment interaction effects can make relative performance
      unpredictable and may hamper selection for resistance to European corn borer. The
      objective of this study was to determine the effect of environment on genotypic
      reaction to European corn borer resistance in maize. A set of 12 maize inbred
      lines was chosen to represent a range of European corn borer responses. Eleven
      testing environments ranged from Delaware, Ohio, Illinois, Iowa, Nebraska,
      Missouri, to Mississippi. For length of stalk tunneling, environmental and
      genotypic main effects (estimated by restricted maximum likelihood) were >20- and
      10-fold larger than their interaction effect, respectively. Length of tunneling
      means for genotypes (across environments) ranged from 10.1 to 35.4 cm. Several
      putatively resistant genotypes grouped with the susceptible checks, B73 and Mol7.
      By breaking factors and the interaction into single degree of freedom components,
      we observed that GEMS-0001 had significant crossover interactions toward less
      susceptibility in both Mississippi and the Nebraska environments. Environments
      displaying several crossover interactions indicated that European corn borer
      screening at these sites would not necessarily apply to other locations, whether
      due to small differences in experimental conduct and/or environmental effects.
      The five most resistant genotypes were fairly consistent across environments.
      Because all environments except Illinois used larvae from the same insectary, and
      these environments differed in damage intensity and rankings, it is unlikely that
      insect biotype was a factor contributing to genotype-by-environment effects.

PMID- 15568369
TI  - Fixed precision sampling plans for white apple leafhopper (Homoptera:
      Cicadellidae) on apple.
AB  - Constant precision sampling plans for the white apple leafhopper, Typhlocyba
      pomaria McAtee, were developed so that it could be used as an indicator species
      for system stability as new integrated pest management programs without broad
      spectrum pesticides are developed. Taylor's power law was used to model the
      relationship between the mean and the variance, and Green's constant precision
      sequential sample equation was used to develop sampling plans. Bootstrap
      simulations of the sampling plans showed greater precision (D = 0.25) than the
      desired precision (Do = 0.3), particularly at low mean population densities. We
      found that by adjusting the Do value in Green's equation to 0.4, we were able to
      reduce the average sample number by 25% and provided an average D = 0.31. The
      sampling plan described allows T. pomaria to be used as reasonable indicator
      species of agroecosystem stability in Washington apple orchards.

PMID- 15568370
TI  - F2 screen variations and associated statistics.
AB  - The F2 screen is a flexible methodology used to estimate the frequency of
      resistance alleles (R) in an insect population. We have developed several
      alternative protocols, along with the associated statistics, to conduct an F2
      screen with mated or unmated individuals, random and nonrandom mating of F1
      adults, and the screening of multiple lines together in the F2 screen. Our
      protocols describe how to perform and analyze an F2 screen starting with unmated
      P1 as an alternative to mated females. A randomly mated population of > or = 50
      F1 adults should be sufficient to detect R alleles > 99% of the time. If
      nonrandom mating occurs in the F2 screen, it is most likely to be positive
      assortative mating, and this would improve the probability of detecting an R
      allele. Pair mating the F1 adults greatly increases costs of the screen while
      providing a small, but negligible improvement in detecting R alleles. The number
      of screens may be reduced by more than two-thirds by screening multiple lines
      together. These methodological variants show the F2 screen to be much more robust
      than originally described.

PMID- 15568371
TI  - Control of sawtoothed grain beetles (Coleoptera: Silvanidae) in stored oats by
      using an entomopathogenic fungus in conjunction with seed resistance.
AB  - We tested the hypothesis that the entomopathogenic fungus Beauveria bassiana
      would be more efficacious on oat cultivars that prolonged the immature
      developmental period of sawtoothed grain beetle, Oryzaephilus surinamensis (L.),
      a storage pest. However, percentage of reduction in progeny production was
      similar on whole 'Don' and 'Paul' oats treated with fungus, even though immature
      developmental time was longer on whole 'Don' than on 'Paul' oats. In our initial
      test at 10 mg of conidia per kilogram of oats, the number of beetle progeny
      produced was reduced by 38-67% in whole oats, and there was no effect of the
      fungus on insects developing on cracked oats. Therefore, we conducted two dose
      response studies that showed that adding 150 mg of conidia per kilogram to
      cracked or whole 'Paul' oats resulted in a 70 and 98% reduction, respectively, in
      number of progeny produced. No further reduction was obtained by adding 200 mg of
      conidia per kilogram of cracked or whole 'Paul' oats. Presence of the fungus did
      not affect developmental time in any of our tests. A previous study showed that
      cleaned oats should limit insect population growth to allow long-term storage of
      oats without insect damage. However, the current study shows that if the oats are
      not cleaned, and not cleaning oats is the normal storage practice, then B.
      bassiana could be used to help control sawtoothed grain beetles.

PMID- 15568372
TI  - Building bridges. Conference brings together veterinary leaders from the U.S.,
      Iraq, Afghanistan, and Kuwait.

PMID- 15568373
TI  - AVMA leadership holds listening session in nation's capital.

PMID- 15568374
TI  - Catching up with communication.

PMID- 15568375
TI  - Battling baby turtle sales.

PMID- 15568376
TI  - More on the sentient property debate.

PMID- 15568377
TI  - More on the sentient property debate.

PMID- 15568378
TI  - A reminder to show empathy to grieving pet owners.

PMID- 15568379
TI  - Comments on diagnosis in dentistry article.

PMID- 15568380
TI  - Comments on diagnosis in dentistry article.

PMID- 15568381
TI  - Comments on diagnosis in dentistry article.

PMID- 15568382
TI  - What is your diagnosis? Hepatozoonosis.

PMID- 15568383
TI  - What is your diagnosis? Myositis ossificans.

PMID- 15568384
TI  - Theriogenology question of the month. Acute peritonitis secondary to intra
      abdominal semen deposition.

PMID- 15568385
TI  - Current status of aquatic species biologics.
AB  - No vaccine is a substitute for good management and diligent biosecurity in an
      aquaculture facility. It is always important to ensure the best water quality
      possible, provide quality nutrition, avoid overcrowding of tanks and raceways,
      remove dead fish to prevent pathogen buildup and spread, and reduce or eliminate
      unnecessary stress on fish. Use of a preventive medicine vaccine program and
      improved management can help ensure good health in a fish population and reduce
      the industries' use of therapeutic agents.

PMID- 15568386
TI  - Comparison of direct immunofluorescence, modified acid-fast staining, and enzyme
      immunoassay techniques for detection of Cryptosporidium spp in naturally exposed
      kittens.
AB  - OBJECTIVE: To evaluate a modified Ziehl-Neelsen acid-fast staining technique
      (mZN), a direct immunofluorescence detection procedure (DIF), and 3 commercial
      enzyme immunoassays (EIAs) for detection of Cryptosporidium oocysts in fecal
      specimens from kittens. DESIGN: Prospective study. SAMPLE POPULATION: 416 fecal
      specimens collected from 104 randomly selected domestic shorthair kittens (8 to
      16 weeks of age) that were naturally exposed to Cryptosporidium spp. PROCEDURE:
      Fresh fecal specimens were collected once daily for 4 consecutive days and
      processed immediately. Sensitivities of mZN, DIF, and 3 commercial EIAs (EIA-1,
      EIA-2, and EIA-3) were estimated and compared. RESULTS: EIA-2 had the highest
      sensitivity on day 1 (89%), followed by EIA-1 (80%), and mZN (72%). EIA-3 had the
      lowest sensitivity on day 1 (15%). EIA-2, EIA-1, and mZN had similar
      sensitivities after 2 consecutive fecal examinations (approx 90%). Determination
      of specificities was compromised by the small number of cats that had negative
      results for all tests (n = 3). CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that EIA-2 and EIA-1 had the highest sensitivities when only a single
      fecal specimen was examined; however, mZN and EIA-1 had similar sensitivities
      when 2 consecutive fecal specimens were examined. The higher costs of EIA-2 and
      EIA-1 may be offset by the tests' high sensitivity, simplicity of use, and ease
      of interpretation and by savings in technician time.

PMID- 15568387
TI  - Effects of passive transfer of immunity on results of diagnostic tests for
      antibodies against feline immunodeficiency virus in kittens born to vaccinated
      queens.
AB  - OBJECTIVE: To determine whether passive transfer of immunity affects results of
      diagnostic tests for antibodies against FIV in kittens born to vaccinated queens.
      DESIGN: Experimental trial. ANIMALS: 12 specific-pathogen-free queens and their
      55 kittens. PROCEDURE: Queens were vaccinated with a whole-virus FIV vaccine
      prior to breeding. Serum was obtained from the queens on the day of parturition
      and from the kittens on days 2 and 7, then weekly until results of tests for
      antibodies against FIV were negative for 2 consecutive weeks. Milk was collected
      from the queens daily for the first week and then weekly. Serum and milk were
      tested for antibodies against FIV with 2 commercial assays. RESULTS: Antibodies
      against FIV were detected in serum obtained from the queens on the day of
      parturition and in the milk throughout lactation. All kittens tested positive for
      antibodies against FIV at 2 days of age. At 8 weeks of age, 30 (55%) kittens
      tested positive with 1 of the commercial assays, and 35 (64%) tested positive
      with the other. All kittens tested negative for antibodies against FIV by 12
      weeks of age. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that kittens
      readily absorb antibodies against FIV in colostrum from vaccinated queens and
      that these antibodies may interfere with results of commercially available tests
      for FIV infection past the age of weaning. Currently licensed diagnostic tests
      for FIV infection are unable to distinguish among kittens with antibodies against
      FIV as a result of infection, passive transfer from infected queens, and passive
      transfer from vaccinated queens.

PMID- 15568388
TI  - Effect of vaccination against feline immunodeficiency virus on results of
      serologic testing in cats.
AB  - OBJECTIVE: To determine the effect of vaccination against FIV on results of
      serologic assays for FIV infection. DESIGN: Prospective clinical trial. ANIMALS:
      26 specific-pathogen-free cats, 102 laboratory-reared cats (42 unvaccinated and
      uninfected, 41 vaccinated and uninfected, and 19 infected with FIV), and 22
      client-owned cats infected with FIV. PROCEDURE: To determine the onset and
      duration of anti-FIV antibody production in cats following vaccination with a
      whole-virus vaccine, serum was obtained from the 26 specific-pathogen-free cats
      prior to vaccination and weekly for 10 weeks, then monthly for 52 weeks, after
      vaccination; serum was tested for anti-FIV antibodies with lateral flow and
      microwell plate ELISAs. To determine the diagnostic performance of serologic
      assays for FIV infection, plasma from uninfected, unvaccinated cats; uninfected,
      vaccinated cats; and FIV-infected cats was tested for FIV antibodies with the 2
      ELISAs, a western blot assay, and an immunofluorescence antibody assay and for
      FIV antigen with an ELISA. RESULTS: Anti-FIV antibodies were detected in all 26
      vaccinated cats 1 year after vaccination. Sensitivity of the antibody assays for
      FIV infection was high (98% to 100%). Specificity was high in unvaccinated cats
      (90% to 100%) but poor in vaccinated cats (0% to 54%). None of the vaccinated or
      infected cats had detectable FIV antigen in plasma. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that vaccination against FIV causes false-positive
      results for at least 1 year with currently available serologic assays for FIV
      infection. Negative FIV antibody assay results are highly reliable for detection
      of uninfected cats, but positive results should be interpreted with caution.

PMID- 15568389
TI  - Histologic comparison of skin biopsy specimens collected by use of carbon dioxide
      or 810-nm diode lasers from dogs.
AB  - OBJECTIVE: To compare histologic artifacts caused by carbon dioxide (CO2) or 810
      nm diode surgical lasers used to obtain small biopsy specimens of skin from
      healthy dogs. DESIGN: Prospective study. ANIMALS: 4 dogs. PROCEDURE: 21 skin
      biopsy specimens were collected from each dog. Three biopsy specimens were
      obtained with a CO2 or an 810-nm diode laser at 3 operating settings each, and 3
      biopsy specimens were obtained with a 6-mm biopsy punch instrument (controls).
      After processing, biopsy specimens were examined for artifacts related to laser
      tissue interactions. Microscopically visible char was measured from the lateral
      edge of each specimen obtained with a laser. RESULTS: There were no significant
      differences among mean char distances in biopsy specimens obtained with the CO2
      laser at various settings. Mean char distance was significantly greater in all
      skin biopsy specimens obtained with the diode laser, compared with those obtained
      with the CO2 laser. Mean char distance was significantly greater in biopsy
      specimens obtained with the 810-nm diode laser at high power, compared with
      biopsy specimens obtained with the 810-nm diode laser at low power. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results indicated that the CO2 laser caused less thermal
      injury at margins of skin biopsy specimens; therefore, if a surgical laser is
      used for removal of cutaneous masses or to obtain skin biopsy specimens, use of
      the CO2 laser is recommended. Veterinarians performing a biopsy by using a
      surgical laser should be aware that laser-induced artifacts may render small
      biopsy specimens useless for providing accurate histologic diagnosis.

PMID- 15568390
TI  - Stereotactic radiosurgery for treatment of osteosarcomas involving the distal
      portions of the limbs in dogs.
AB  - Stereotactic radiosurgery (SRS) involves precise delivery of a single large dose
      of radiation to a designated tumor target. This report describes use of SRS in
      combination with a frameless stereotactic localization system to treat 11 dogs
      with appendicular osteosarcomas. Five dogs were treated with SRS alone; 6 were
      treated with a combination of SRS and chemotherapy. Overall median survival time
      was 363 days (range, 145 to 763 days), with 6 dogs still alive 90, 142, 234, 367,
      633, and 763 days after SRS. Limb function was good or excellent in all 6 dogs
      that were still alive. Results in these dogs suggest that SRS may be a viable
      option for dogs with appendicular osteosarcoma, with the potential to provide
      long-term local tumor control and improvement in limb function, especially when
      combined with chemotherapy. Because of the destructive nature of osteosarcoma and
      limitations of SRS, dogs with tumors that are small and have caused minimal bone
      destruction would likely be the best candidates for this procedure.

PMID- 15568391
TI  - Putative transmission of Mycobacterium tuberculosis infection from a human to a
      dog.
AB  - A 3.5-year-old Yorkshire Terrier was evaluated for anorexia and vomiting;
      infection with Mycobacterium tuberculosis was diagnosed by use of histology,
      bacteriologic culture, and polymerase chain reaction (PCR) assay on various
      tissues. The dog was living with a human with an established M. tuberculosis
      infection. Findings were unique in that diagnosis of M. tuberculosis infection
      was obtained via PCR techniques, and isolates from the owner and dog were matched
      via restriction fragment length polymorphism fingerprinting. Dogs infected with
      M. tuberculosis from humans are most commonly infected via the respiratory tract.
      Clinical signs in dogs are variable and depend on the integrity of the immune
      system and the degree of dissemination. Diagnosis can often be obtained through
      histopathology and bacteriologic culture; additional diagnostic techniques are
      also available. Treatment of a dog with confirmed M. tuberculosis infection is
      controversial, and at least 6 months of multidrug treatment is required.

PMID- 15568392
TI  - Use of high-power ultrasonic shears for laparoscopic ovariectomy in mares.
AB  - A method for performing laparoscopic ovariectomy with high-power ultrasonic
      shears in mares is described, along with results in 10 mares. Briefly, after
      epidural administration of detomidine and local anesthesia with mepivacaine, 3
      cannulas were placed in each paralumbar fossa. A laparoscope was placed through
      the most dorsal cannula, and a grasping forceps was placed through the most
      ventral cannula and used to grasp and manipulate the ovary. The ultrasonic shears
      was then placed through the middle cannula. The jaws of the ultrasonic shears
      were closed across a portion of the ovarian pedicle, and the instrument was
      discharged until tissue within the jaws was transected; the process was repeated
      until the entire ovarian pedicle was transected. Following removal of the right
      ovary, it was passed to the left side of the abdomen and both ovaries were
      removed through an incision in the left paralumbar fossa. No major complications
      were identified in any of the 10 mares. However, excessive bleeding necessitating
      reapplication of the ultrasonic shears (2 ovaries) or application of ligating
      clips (8) was encountered with 10 of the 20 ovaries. Laparoscopic ovariectomy
      with a high-power ultrasonic shears appears to be safe in mares.

PMID- 15568393
TI  - A lag-screw technique for bridging of the medial aspect of the distal tibial
      physis in horses.
AB  - A lag-screw technique for transphyseal bridging of the medial aspect of the
      distal tibial physis in foals with tarsal valgus deformities and results of the
      technique in 11 foals (6 with bilateral tarsal valgus deformities and 5 with
      unilateral tarsal valgus deformities) are described. Briefly, horses were
      anesthetized, and a single stab incision was made through the skin to the
      underlying bone over the most distal aspect of the medial malleolus. A 20-gauge
      needle was placed in the incision to guide screw placement, and a lag screw was
      inserted parallel to the medial cortex of the tibia under radiographic guidance.
      Screws were removed when the tarsal valgus deformity was clinically assessed to
      have improved by at least 80%. Clinically, all horses had evidence of a tarsal
      valgus deformity of > 7 degrees prior to surgery. Mean age at the time of lag
      screw implanation was 220 days (range, 116 to 364 days). Mean time the implant
      was in place was 62 days (range, 39 to 89 days). The tarsal valgus deformity
      resolved in all 11 horses with excellent cosmetic results.

PMID- 15568394
TI  - Occam's razor cuts out the mind-body dichotomy.
AB  - Psychiatric symptoms are among the most common manifestations of endocrine
      disorders. We present a case of Schmidt's syndrome, or polyglandular type II
      failure. Due to a florid psychiatric presentation, the initial endocrine
      diagnosis was missed, and a diagnosis of a nonorganic psychotic illness was made.
      This impacted on the treatment and appropriate placement of the patient. This
      case is presented to illustrate the importance of the organic work-up and follow
      up on abnormal laboratory results in patients with dementia. In the elderly, a
      new onset of psychosis is usually associated with an organic cause. Furthermore,
      the presence of either a fixed or intermittent change in cognitive function
      suggests a strong likelihood of organicity. These features were present, but not
      noted, leading to management problems that are described here to illustrate the
      need for careful clinical scrutiny.

PMID- 15568395
TI  - Numbers can lie except when they are zero.

PMID- 15568396
TI  - The social impact of medicine--Chapter 24.
AB  - This paper, an overview of medical history, is based on a course I taught at the
      University of Delaware's Academy of Life Long Learning, "Medicine, the Old and
      the New." It will not be a chronology of medical events and discoveries, but a
      discussion of the social aspects of medicine, how medicine affected the everyday
      lives of people, from the religion-based medicine of antiquity to the super
      scientific medicine of today. This paper is a compilation of other historical
      papers including, but not limited to, those listed in the accompanying
      bibliography. It is not an original paper. This paper will consist of 25
      chapters. Dr. Peter V. Rocca, Editor-in-Chief of the Delaware Medical Journal
      (DMJ), is planning to publish one chapter in each successive issue of the DMJ.

PMID- 15568397
TI  - Response to "above all, do no harm".

PMID- 15568398
TI  - 2003 ISSVD terminology and classification of vulvodynia: a historical
      perspective.

PMID- 15568399
TI  - Pimecrolimus for the treatment of vulvar lichen sclerosus: a report of 4 cases.
AB  - BACKGROUND: Lichen sclerosus is a chronic cutaneous disorder with a predilection
      for the vulva. The etiology is unknown. Superpotent topical corticosteroids are
      the most effective treatment. Dermal atrophy, however, is a well-known
      complication associated with changes of lichen sclerosus superpotent topical
      corticosteroids. In addition, some women do not respond adequately to topical
      steroids. Therefore, a treatment regimen that does not rely on corticosteroids
      may be beneficial. As lichen sclerosus is a T-lymphocyte-mediated disorder, it
      has been suggested that a topical macrolide immunosuppressant, such as
      pimecrolimus, may be a safe and effective alternative treatment for lichen
      sclerosus. Since pimecrolimus does not affect collagen synthesis, it does not
      cause thinning of the dermis. CASES: Four patients with biopsy-proven lichen
      sclerosus were treated with 1% pimecrolimus cream twice daily. At the end of 3
      months of treatment, 3 of the 4 patients reported complete resolution of their
      symptoms of vulvar itching and burning. Two patients had repeat vulvar biopsies
      at the end of treatment that showed reversal of the histologic changes of lichen
      sclerosus. CONCLUSION: In this small series, pimecrolimus appeared to be a safe
      and effective treatment of vulvar lichen sclerosus. A randomized, controlled
      trial comparing pimecrolimus and clobetasol propionate should be performed to
      determine which is the safer and more effective medication for the long-term
      treatment of lichen sclerosus.

PMID- 15568400
TI  - Clinical variability of bacterial vaginosis and trichomoniasis.
AB  - Bacterial vaginosis and trichomoniasis are two of the most commonly encountered
      vaginal diseases. Although risk factors for both vaginal conditions have been
      identified, there continues to be lack of knowledge in regard to their role in
      association with other sexually transmitted diseases. Vaginal pH is an essential
      ingredient in the defense and control of the vaginal environment. The alteration
      of pH with the sequelae of such pregnancy complications as preterm delivery,
      preterm labor and premature rupture of the membranes; amniotic fluid infection;
      postpartum endometritis and surgical infections; and the role of bacterial
      vaginosis are discussed. Treatment modalities in both the nonpregnant and
      pregnant woman, as well as treatment of resistant cases of both vaginal
      conditions, are recommended.

PMID- 15568401
TI  - Immunohistologic detection of nm23-H1 protein in squamous cell carcinoma of the
      vulva.
AB  - OBJECTIVE: To analyze nm23-H1 protein immunohistologically in squamous cell
      carcinoma of the vulva. STUDY DESIGN: In 68 carcinomas, tumor type, grade,
      inflammation and vascular space involvement were determined. Formalin-fixed,
      paraffin-embedded tissue was stained for nm23-H1. Staining pattern, intensity and
      percentage of stained tumor cells were evaluated. Staining results were analyzed
      statistically univariately by the chi2 test, Kaplan-Meier survival analysis with
      log-rank test and receiver operator characteristic curves and multivariately by
      proportional hazard analysis. RESULTS: Of the tumors, 9% were negative for nm23
      H1. Positive tumors showed 4 staining patterns. Tumors with inhomogeneous
      expression of nm23-H1 tended to have shorter disease-free and overall survival.
      Carcinomas with nm23-H1 staining in <50% of the tumor cells more frequently
      developed nonlocal tumor recurrences (p= 0.018) and showed shorter disease-free
      survival (p = 0.017). Tumors with high nm23-H1 expression were associated with
      patients younger than 60 years (p = 0.02). CONCLUSION: Immunohistologic staining
      for nm23-H1 protein shows different staining patterns and percentages of stained
      cells in squamous cell carcinoma of the vulva. Tumors with inhomogeneous and low
      nm23-H1 expression are associated with a worse prognosis.

PMID- 15568402
TI  - Human papillomavirus, Epstein-Barr virus and p53 mutation in vulvar
      intraepithelial neoplasia.
AB  - OBJECTIVE: To clarify the role of human papillomavirus (HPV) and Epstein-Barr
      virus (EBV) infection in vulvar carcinogenesis in relation to the mutated p53
      gene. STUDY DESIGN: Polymerase chain reaction (PCR) was used to amplify DNA
      sequences of the viruses and PCR-single-strand conformation polymorphism analysis
      to screen for p53 gene mutations in exons 5-8 from formalin-fixed, paraffin
      embedded blocks including 10 undifferentiated vulvar intraepithelial neoplasia
      (VIN) specimens. RESULTS: HPV and EBV DNA was found in 75% (6/8) and 0% (0/10) of
      VIN tissues, respectively. Oncogenic HPV 16 was the predominant type. HPV DNA
      extraction was not possible in 2 VIN specimens. p53 Gene mutation was shown in
      20% (2/10) of VIN lesions. No correlation was found between p53 gene mutation the
      presence of viral HPV or EBV DNA. Mutated p53 was equally distributed between HPV
      positive and -negative VIN cases. CONCLUSION: Our results suggest that although
      most undifferentiated VIN lesions are associated with HPV infection, p53
      mutations may occur independent of viral infection even in the presence of
      oncogenic HPV. HPV, but not EBV or p53 gene mutation, can play a role in the
      pathogenesis of undifferentiated VIN.

PMID- 15568403
TI  - Activated lactoferrin and fluconazole synergism against Candida albicans and
      Candida glabrata vaginal isolates.
AB  - OBJECTIVE: To evaluate the fungistatic activity of activated lactoferrin (ALF),
      fluconazole (FCN) individually and in combination against Candida vaginal
      isolates as well as to measure the time to recovery from the fungistatic effects
      after exposure in vitro to threshold minimal inhibitory concentrations (MIC).
      STUDY DESIGN: Fungistasis patterns for ALF (2.5 mg/mL) and FCN (0.25 mg/mL) were
      tested at threshold MIC against vaginal isolates of C albicans (n = 5) and C
      glabrata (n = 5) grown in Sabouraud's dextrose broth against 10(5) yeast inoculum
      at 37 degrees C for 48 hours by microscale optical density (OD) assay according
      to the following criteria: "Total stasis" indicates that an agent elicited no
      change or a change in turbidity <0.1 OD unit for >48 hours (complete growth
      inhibition), "stasis recovery" (SR) is the time point at which turbidity of a
      previous stasis system shows an upward growth trend for >0.1 OD unit (recovery
      from growth inhibition), and "partial stasis" (PS) is proliferation after stasis
      recovery, measured as a percentage relative to growth control at any time
      (incomplete growth inhibition). RESULTS: For ALF (2.5 mg/mL), the mean SR time
      was 15.6 +/- 2 hours for C albicans (n = 5) and 27.5 +/- 2 hours for C glabrata
      (n = 5). The SR patterns for FCN were strain dependent and showed a wide range of
      deviation for both Candida species; accordingly, the values were 15.8 +/- 9 hours
      for C albicans and 25.5 +/- 12 hours for C glabrata. After 48 hours exposure to C
      albicans, ALF and FCN elicited a mean PS of 27.5 +/- 2% and 24.8 +/- 7%,
      respectively. The PS values at 48 hours showed a marked variation between C
      glabrata isolates, 29.1 +/- 24% for ALF and 21.5 +/- 38% for FCN. However, a
      combination of ALF and FCN at their threshold MIC showed significant drug
      synergism, causing total stasis of both species of Candida isolates. Thus, no SR
      for any Candida isolate was detected at or beyond 48 hours. Conversely, native
      lactoferrin failed to demonstrate such potent synergism with FCN against either
      Candida species. CONCLUSION: The combination of ALF and FCN at the threshold MIC
      elicited potent synergism, leading to total fungistasis of C albicans and C
      glabrata vaginal pathogens. ALF is a new class of fungistatic agent with a mode
      of action distinct from that of azoles.

PMID- 15568404
TI  - Clinically identifying women with vulvar lichen sclerosus at increased risk of
      squamous cell carcinoma: a case-control study.
AB  - OBJECTIVE: To identify clinical factors that might identify women with vulvar
      lichen sclerosus who are at increased risk of developing squamous cell cacinoma.
      STUDY DESIGN: A retrospective, case-control study compared 46 women presenting
      between 1992 and 2000 with clinical and histologic evidence of squamous cell
      carcinoma of the vulva arising in a background of lichen sclerosus and 213 new
      referrals with vulvar lichen sclerosus during the same period. RESULTS: The ages
      of the patients and presence of clinical hyperplasia were the only differences
      between the 2 groups. CONCLUSION: Women presenting with vulvar cancer arising
      within a background of lichen sclerosus are significantly older than women
      presenting with lichen sclerosus. In addition, clinical evidence of squamous
      hyperplasia is independently associated with vulvar carcinoma. Neither the
      presence nor duration of symptoms nor the loss of vulvar architecture is a useful
      indicator of potential cancer risk.

PMID- 15568405
TI  - Role of multiple births in very low birth weight and infant mortality.
AB  - OBJECTIVE: To determine the percentage of very-low-birth-weight (VLBW) infants
      (<1500 g) and infant deaths attributable to multiple births in the general
      population and in women aged 35+. STUDY DESIGN: The year 2000 Massachusetts birth
      certificate database with linked births-deaths was examined. Etiologic fractions
      (EF) for VLBW and infant mortality attributable to multiples were calculated for
      the general population and the 35+ age group. The percentages of multiples
      occurring in the 35+ age group were calculated. Infant deaths due to congenital
      anomalies and "perinatal conditions" were calculated. RESULTS: There were 81,582
      resident births in Massachusetts in 2000. Of them 4.3% were multiples. Of the
      1090 VLBW infants, 26.1% (95% CI: 23.5-28.8) were in twins and 7.7% (95% CI: 6.2
      9.5) in higher-order multiples, yielding an EF of 30.8% for multiples in VLBW. In
      the 35+ age group, the multiple birth ratio was 6.6% (95% CI: 6.3-7.0). The EF
      for multiples and VLBW in this age group was 33.7%. The 35+ age group accounted
      for 32.4% (95% CI: 30.8-34.0) of twins and 45.5% (95% CI: 39.1-52.0) of higher
      order multiples born in 2000. Of the 392 infant deaths, 57 (14.6%; 95% CI: 11.2
      18.4) were attributed to congenital anomalies, and 236 (60.2%; 95% CI: 55.2-65.0)
      to "perinatal conditions." Multiples were responsible for 8 (14%; 95% CI: 6.3
      25.8) of deaths due to anomalies, and 73 (30.9%; 95% CI: 25.1-37.3) due to
      "perinatal conditions." CONCLUSION: Over 30% of VLBW infants, nearly 20% of
      infant mortality and >30% of infant mortality due to perinatal conditions could
      be attributed to multiples. Multiple pregnancy is a significant public health
      problem.

PMID- 15568406
TI  - Mutagenicity of vaginal spermicides containing nonoxynol-9 in a bacterial assay.
AB  - OBJECTIVE: To evaluate the potential mutagenicity of 3 commonly used over-the
      counter spermicidal gels containing nonoxynol-9 as the active ingredient. STUDY
      DESIGN: The gels were examined for their ability to produce mutations in a
      bacterial assay (Ames test). The results were compared with those from testing a
      series of nonantibacterial and antibacterial personal prwhen there is
      antibacterial personal products that come into contact with mucous membranes as
      well as some caustic, nonpersonal home products and a known mutagen. RESULTS: All
      3 spermicidal gels were as mutagenic or more mutagenic than the other products
      tested in each category. Although activation by liver extract was required for 2
      of the gels to show mutagenicity in this assay, the third was mutagenic without
      liver activation. CONCLUSION: Because of the intimate contact of spermicidal gels
      with human gametes and the possibility that components of the gels may be
      absorbed systemically and reach the unfertilized or fertilized ovum, the fact
      that these gels have mutagenic potential raises concern in cases in which
      conception occurs.

PMID- 15568407
TI  - Excretion of pantoprazole in human breast.
AB  - OBJECTIVE: To measure the amount of pantoprazole in human milk following its oral
      administration to a breast-feeding mother and to estimate human exposure. STUDY
      DESIGN: One woman was studied over a 24-hour interval after oral administration
      of 40-mg pantoprazole. Serial plasma and milk samples were collected over 24
      hours, and pantoprazole concentrations were measured by high-performance liquid
      chromatography. A milk/plasma ratio of 0.022 was observed at tmax, 2 hours after
      dose administration. Infant exposure was measured as maximum concentration in
      milk multiplied by an estimated maximum consumption of 200 mL at this time.
      RESULTS: The relative infant dose was estimated to be 7.3 microg of pantoprazole,
      which is equivalent to 0.14% of the weight-normalized dose received by the
      mother. Because pantoprazole is unstable in acidic pH, the systemic dose received
      by the infant is expected to be lower if the ingested pantoprazole is exposed to
      acid in the infant's stomach. The mother detected no adverse events in the
      infant. CONCLUSION: These limited data show that pantoprazole is minimally
      excreted into breast milk. While it is not known if pantoprazole affects breast
      milk production, women who are breast-feeding do not have to stop breastfeeding
      when taking pantoprazole chronically.

PMID- 15568408
TI  - Analgesic efficacy of French maritime pine bark extract in dysmenorrhea: an open
      clinical trial.
AB  - OBJECTIVE: To clarify the effect of Pycnogenol (Horphag Research, Switzerland),
      French maritime pine bark extract, on menstrual pain. STUDY DESIGN: We treated 47
      patients with menstrual pain, aged 21-45 years, with Pycnogenol at 30 mg (2
      capsules) orally twice a dysmenorrl day. The administration of Pycnogenol began
      on the eighth day of the first menstrual cycle and continued until the seventh
      day of the third menstrual cycle. Improvement was evaluated by measuring scores
      of symptoms during the first and second, and first and third menstrual cycle
      using the Wilcoxon rank sum test. RESULTS: Treatment with Pycnogenol lowered the
      pain scores for abdominal pain significantly (p < 0.05) as compared to
      pretreatment values. Pain relief in the second cycle of treatment was better as
      compared to the first cycle of treatment, as indicated by a higher level of
      significance (p < 0.01) and lower median pain score. The number of days with
      abdominal pain showed a trend toward fewer days with pain; however, the
      difference failed to reach significance. Relief of back pain was not that
      pronounced during the first cycle treated with Pycnogenol; the pain scores were
      not significantly different from those in the pretreatment period. However,
      continuation of treatment during the second cycle produced significant pain
      relief (p < 0.01). The number of days with back pain decreased. The number of
      days with pain was significantly lower (p < 0.01) in the second cycle of
      treatment with Pycnogenol. CONCLUSION: Pycnogenol has a potential analgesic
      effect on menstrual pain.

PMID- 15568409
TI  - Septate uterus with a double cervix and longitudinal vaginal septum.
AB  - OBJECTIVE: To report the clinical features of 9 cases and review the previously
      reported 8 cases of an uncommon mullerian anomaly, characterized by the presence
      of a complete uterine septum with cervical duplication and represent a a
      longitudinal vaginal septum. STUDY DESIGN: Retrospective clinical study. RESULTS:
      Nine patients aged 21-32 presented to our clinic with complaints of dyspareunia,
      dysmenorrhea, and primary or secondary infertility. All 9 patients displayed a
      single uterus with smooth fundal contour, double cervix and longitudinal vaginal
      septum. Some additional abnormal findings were associated with these anomalies in
      some patients: polycystic ovaries in 3 cases and different degrees of
      endometriosis in 2 cases. Most of the patients had normal tubal patency.
      CONCLUSION: According to a MEDLINE search, only 8 cases of septate uterus with
      cervical duplication and a longitudinal vaginal septum have been reported to
      date. We report 9 more cases, which suggest that this atypical septate uterus
      type is probably more frequent than reported. These cases support the
      bidirectional mullerian theory and may imply the presence of another type of
      mullerian anomaly.

PMID- 15568410
TI  - Estrogen and combined hormone therapy for women after genital malignancies: a
      review.
AB  - This review summarizes information regarding estrogen therapy (ET) and hormone
      therapy (HT) for women with endometrial cancer as well as other gynecologic
      malignancies. The cumulative experience from 4 case-control studies consists of
      537 affected women. Of the 228 patients who received estrogen therapy, 3.5%
      developed recurrences as opposed to 16.5% among the 309 women receiving no
      therapy. Administration of ET at an early stage of disease is therefore
      appropriate if a few conditions are fulfilled. The impact of estrogen on other
      gynecologic malignancies is not as evident. As to ovarian cancer, the information
      on hormone employment is scantier and derives mainly from statistical analysis of
      data on healthy users of estrogen alone or combined with progestin. Several age
      matched, case-control studies and 4 meta-analyses disclosed a higher rate, though
      not significant, of the later development of ovarian cancer among hormone users.
      Focusing on patients with disease, 2 trials conducted so far have failed to
      demonstrate any change in survival or mortality from ET or HT. It is agreed,
      however, that the histologic type of the tumor is an important factor to consider
      prior to the initiation of such therapy. The current literature permits ET in
      most cases of ovarian cancer, but further studies are needed to clearly delineate
      specific contraindications. Utilizing estrogen compounds has no bearing on risks
      of later developing squamous cell carcinoma of the cervix, or tubal, vulvar or
      vaginal cancer. Those conditions do not seem to contraindicate later employment
      of ET or HT. A previous history of cervical adenocarcinoma, however, definitely
      prohibits the use of these hormonal regimens.

PMID- 15568411
TI  - Erosion of a B-Lynch suture through the uterine wall: a case report.
AB  - BACKGROUND: The B-Lynch uterine suture brace has been used for the surgical
      treatment of postpartum hemorrhage. To date, no complications of this procedure
      have been reported. We describe B-Lynch suture erosion through the uterine wall
      identified at a 6-week postpartum visit. CASE: A 19-year-old primigravida
      underwent a primary low transverse cesarean section at term for arrest of
      descent. The surgery was complicated by postpartum hemorrhage secondary to
      uterine atony unresponsive to medical management. The patient underwent
      successful placement of a B-Lynch suture using delayed, absorbable suture for
      control of the hemorrhage and had an uneventful postoperative course. At her 6
      week postpartum examination, she was found to have the suture protruding from the
      uterine cervical os. The suture was removed in its entirety without difficulty.
      Follow-up sonohysterography at 6 months identified a small defect in the anterior
      wall of the lower uterine segment, corresponding to the probable site of suture
      erosion. CONCLUSION: Erosion of suture through the uterine wall can be a
      complication of the B-Lynch uterine suture brace. Delayed, absorbable suture is
      less desirable than absorbable suture for this procedure due to the risk of
      erosion through the uterine wall.

PMID- 15568412
TI  - Fetal bones retained in the uterine cavity as a rare cause of chronic pelvic
      pain: a case report.
AB  - BACKGROUND: Intrauterine retention of fetal bones is a rare complication of
      abortion. Abnormal uterine bleeding, dysmenorrhea and secondary infertility are
      the usual complaints. In this case the prolonged retention of fetal bones caused
      chronic pelvic pain. Hysteroscopic removal of the bones resulted in resolution of
      the chronic pelvic pain. CASE: A 20-year-old woman with a history of multiple
      terminations of pregnancies, was seen in the clinic with a complaint of chronic
      pelvic pain. Ultrasound and sonohysterogram revealed the presence of a foreign
      body in the uterine cavity. Hysteroscopic removal of fetal bones was performed,
      and the patient's pelvic pain was resolved. CONCLUSION: Intrauterine retention of
      fetal bones may result in chronic pelvic pain. In patients with history of
      abortion, the presence of fetal bones may cause chronic pelvic pain.

PMID- 15568413
TI  - Transcatheter occlusion of patent foramen ovale: a prevention for decompression
      illness?

PMID- 15568414
TI  - Transient osteoporosis associated with hyperhomocystinemia: a possible role for
      hyperbaric oxygen therapy.
AB  - Transient osteoporosis of the hip is considered by some to be an early stage of
      avascular necrosis. Hyperbaric oxygen (HBO2) therapy, which may be of benefit in
      the treatment of avascular necrosis, might therefore be used in the treatment of
      transient osteoporosis of the hip. We present a case of transient osteoporosis
      associated with elevated levels of homocysteine in a 33-year-old white male, who
      was treated by HBO2. Treatment was administered at 2.5 ATA for 90 minutes once
      daily, five days per week. Regular follow-up examinations in the course of the
      HBO2 therapy revealed improvement in the patient's complaints and the findings of
      the physical examination. Repeated magnetic resonance imaging (MRI) performed
      after 40 and 90 sessions showed decreased edema and complete resolution of the
      edema, respectively. Evaluation 6 months after the completion of treatment
      revealed complete resolution of symptoms, with a normal physical examination.

PMID- 15568415
TI  - Emphysematous cystitis: rapid resolution of symptoms with hyperbaric treatment: a
      case report.
AB  - INTRODUCTION: Emphysematous cystitis is a rare disease that occurs most often in
      elderly diabetic patients characterized by gas formation in the bladder wall due
      to infection. The infecting organism is usually an aerobic bacterium, most
      commonly E. coli although anaerobic species have also been reported. We report
      the use of hyperbaric oxygen in a patient with emphysematous cystitis and air in
      the femoral vein in which the treatment rapidly resolved the symptoms and
      radiological abnormalities. METHODS: A 65-year-old female presented to the
      Emergency Department with altered mental status, weakness, dark urine, dysuria
      and fever. She was febrile and lethargic. Abdominal exam showed suprapubic
      tenderness. Urinalysis was positive for white blood cells and bacteria. A CT scan
      of the abdomen demonstrated extensive air in the bladder wall with an air bubble
      in the femoral vein. Presumptive diagnosis was urinary tract infection,
      emphysematous cystitis, and sepsis. A question of air embolism was raised due to
      the intravascular gas. The patient was treated with hyperbaric oxygen (2.85 atm
      abs, 90 minutes) on two separate occasions in the first 12 hours. Within 24
      hours, the patient's condition rapidly improved. Repeat CT scan 48 hours after
      admission showed near complete resolution of the emphysematous cystitis. The
      patient grew Klebsiella pneumonia from her urine. CONCLUSIONS: Emphysematous
      cystitis is a rare condition caused by either aerobic or anaerobic bacteria and
      may be associated with both bladder wall and intravascular gas formation.
      Hyperbaric oxygen therapy has not been previously reported as a treatment
      modality. The rapid improvement in our patient may indicate a role for hyperbaric
      oxygen in addition to IV hydration and antibiotics in this disease.

PMID- 15568416
TI  - Hyperbaric oxygen therapy in the treatment of carbon dioxide gas embolism.

PMID- 15568417
TI  - Plasma glucose responses in recreational divers with insulin-requiring diabetes.
AB  - Insulin-requiring diabetes mellitus (IRDM) is commonly described as an absolute
      contraindication to scuba diving. A 1993 Divers Alert Network survey, however,
      identified many active IRDM divers. We report on the plasma glucose response to
      recreational diving in IRDM divers. Plasma glucose values were collected before
      and after diving in IRDM and healthy control divers. Time/depth profiles of 555
      dives in IRDM divers were recorded. IRDM divers had been diving for a mean of
      almost nine years and had diabetes for a mean of over 15 years. No symptoms or
      complications related to hypoglycemia were reported (or observed). Post-dive
      plasma glucose fell below 70 mg x dL(-1) in 7% (37/555) of the IRDM group dives
      compared to 1% (6/504) of the controls (p<0.05). Moderate levels of hyperglycemia
      were also noted in 23 divers with IRDM on 84 occasions. While large plasma
      glucose swings from pre-dive to post-dive were noted, our observations indicate
      that plasma glucose levels, in moderately-controlled IRDM, can be managed to
      avoid hypoglycemia during routine recreational dives under ordinary environmental
      conditions and low risk decompression profiles.

PMID- 15568418
TI  - Biocompatibility: a biomechanical and biological concept in total hip
      replacement.
AB  - The insertion of any implant or prosthesis into bone usually changes the
      biomechanical environment and, thus, alters the stresses and strains applied to
      the bone. Both bone overload and excessive stress protection can result in bone
      resorption. The material and geometry of any implant should be designed to avoid
      excessive flexural mismatch. Incompatibility of materials may result in interface
      and mechanical failure, with the consequent generation of particulate debris,
      subsequent osteolysis and implant failure. Particulate debris can be generated
      from articulating surfaces and from any other modular or fixation interface.
      Larger particles are associated with a foreign body giant cell reaction.
      Polyethylene particles in the size range of 0.5 to 10 microm excite a
      cytochemical reaction that culminates in osteolysis. The precise pathogenesis of
      osteolysis has not been characterised, but it is probable that different
      pathogenetic mechanisms are involved in the different radiological types of
      osteolysis. A large number of very small metallic particles are released from
      metal-on-metal couples. These may cause mutagenic damage (chromatid breaks,
      chromosome translocations, aneuploidy, etc.). In defining implant
      biocompatibility it is essential to consider the biological response both to an
      altered mechanical environment and to the liberation of particulate debris.

PMID- 15568419
TI  - Molecular, clinical and political approaches to the problem of cleft lip and
      palate.
AB  - The oral facial complex in man appears to be exquisitively sensitive to genetic
      and environmental influences which is why clefts of the palate are the most
      common congenital birth anomaly. The development of the palate starts at about
      the 6th week of inter-uterine life and requires development of the palatal
      shelves from the maxillary processes of the first arch, shelf elevation, medial
      edge epithelial breakdown and mesenchyme flow with subsequent establishment of
      osteogenic and myogenic blastemata. This significant level of matrix turnover is
      partly regulated by the matrix metalloproteinases and potentially this could be
      affected by abnormalities in gene function. This may represent a common mechanism
      for a variety of different genes associated with clefting of the palate. The
      measurement of outcomes for children born with a cleft requires a wide input from
      a variety of specialities. The development of these outcome measures requires
      rigorous testing and validation, but it is now possible to use a variety of
      outcome measures to establish clinical standards and this has been done
      nationally. The impact of identifying a need for a change in organisation of
      service delivery was probably underestimated. It is clear that the current
      organisations in the National Health Service struggle to implement change, even
      with a detailed study and hard evidence. Reasons for this are outlined and a
      potential harder hitting strategy for effecting this change is outlined. The move
      towards primary care trusts within the latest reorganisation of the Health
      Service is potentially extremely damaging for specialised services for low
      incidence anomalies.

PMID- 15568420
TI  - Factors involved in abdominal wall closure and subsequent incisional hernia.
AB  - Incisional hernia is a frequent complication of abdominal wall closure with a
      reported incidence of between 5% and 15% following vertical midline incisions at
      one-year follow-up. Evidence from randomised clinical trials and meta-analysis
      indicate that a continuous running non-absorbable or slowly absorbed suture such
      as polydioxanone is the method of choice for abdominal wall closure. Continuous
      polydioxanone has a similar incisional hernia rate to its non-absorbable
      counterparts but causes less chronic pain and wound sinuses. Evidence from
      randomised clinical trials indicates that a lateral paramedian incision is
      associated with a lower incidence of incisional hernia when compared with other
      abdominal incisions. Transverse abdominal incisions have no advantage over
      midline incisions in reducing incisional hernia rate. Although experimental and
      clinical evidence indicate that a greater number of stitches with a suture length
      to wound ratio of at least 4:1 is associated with a lower incidence of incisional
      hernia, there is no evidence from randomised clinical trials to support this.
      Intuitively one may think that putting as little tension as possible on the
      closure is important, but there is no evidence for this. Clinical trials
      evaluating these factors would be difficult to undertake making it important that
      surgeons continue to audit incisional hernia rates following abdominal closure.

PMID- 15568421
TI  - Hormonal and genetic risk factors for breast cancer.
AB  - Breast cancer is a major cause of female morbidity and mortality worldwide. In
      this review, we discuss the hormonal and genetic risk factors associated with
      breast cancer development and describe the currently available models for
      predicting an individual woman's risk. We highlight three more sophisticated
      surrogate markers of life-time oestrogen exposure (plasma oestradiol,
      mammographic breast density, bone mineral density) and propose that these may be
      used to improve estimates of a woman's absolute risk.

PMID- 15568422
TI  - Incidence of benign pathology in patients undergoing hepatic resection for
      suspected malignancy.
AB  - BACKGROUND: Confirming the presence of hepatic or proximal bile duct malignancy
      pre-operatively remains difficult and some patients may undergo surgical
      resection for suspected malignant lesions which subsequently turn out to be
      benign. The aim of this study was to establish whether improvements in pre
      operative staging might better identify this patient population. METHODS:
      Analysis of a prospectively collected database, which has been maintained in our
      unit since 1988. RESULTS: Of 250 consecutive patients undergoing hepatic
      resection for presumed malignancy, 18 (7.2%) were shown to have benign pathology.
      These "false positive" rates were 4 out of 160 (2.5%) resections for colorectal
      metastases, 4 out of 49 (8.2%) resections for other solid hepatobiliary tumours
      and 10 out of 41 (24.4%) resections for hilar cholangiocarcinoma. Four of the 18
      patients (22%) developed post-operative complications but there was no
      postoperative mortality. CONCLUSION: Although hepatic resection remains a
      potentially curative procedure for patients with tumours involving the liver
      parenchyma or proximal bile ducts, pre-operative confirmation of malignancy
      remains difficult. Despite appropriate investigation a subset of patients with
      benign disease will still be subjected to major hepatic resection which should be
      undertaken in a specialist unit.

PMID- 15568423
TI  - Alvarado score: an admission criterion in patients with right iliac fossa pain.
AB  - Appendicitis is an important differential diagnosis in patients with right iliac
      fossa pain. The diagnosis in patients with equivocal signs can be difficult. Many
      patients with suspected appendicitis are admitted for observation. We studied the
      Alvarado scores of 175 patients who presented to the emergency department with
      right iliac fossa pain and found that patients with scores of 4 or less did not
      have appendicitis. We also present an algorithm incorporating the Alvarado score
      for patients with suspected appendicitis.

PMID- 15568424
TI  - Endoluminal graft stenting of peripheral aneurysms: questionable results compared
      with conventional surgery.
AB  - Popliteal and femoral aneurysms can be treated by endoluminal graft stenting,
      instead of conventional surgery. Results in four cases suggest, however, that
      long-term results do not justify an endovascular approach.

PMID- 15568425
TI  - Reduction of nasal fractures under local anaesthesia: an acceptable practice?
AB  - Nasal fractures are among the most common bony injuries and are among the most
      frequent reasons for referral to Otorhinolaryngology departments resulting in
      significant pressure on clinical resources. We present our experience of a Nasal
      Fracture Clinic dedicated to the assessment of nasal injuries. A prospective
      study has been undertaken using questionnaires regarding patient satisfaction and
      acceptability of manipulation under a local anaesthetic (LA). During our three
      month study period 91 new patients with nasal injuries were seen; 43 patients
      were diagnosed to have a displaced nasal fracture requiring reduction. Reduction
      of the nasal fracture under LA was performed in 37 patients. We found that
      manipulation under LA was preferred by 94% of patients over the age of 14 years.
      We achieved a high patient satisfaction rate (80% after three months). The
      discomfort associated with reduction under LA did not exceed that of a minor
      dental procedure. No significant complications were encountered during the study
      period. We conclude that reduction of nasal fractures under LA is a safe and
      attractive alternative to reduction under a general anaesthetic (GA) and frees-up
      valuable clinical resources.

PMID- 15568426
TI  - Percutaneous cementoplasty of acetabular bony metastasis.
AB  - The development of malignant lesions in the acetabulum can lead to painful and
      disabling bone destruction. Lytic metastases of the acetabulum are frequent,
      causing pathologic fractures, pain and disability. The literature is sparse in
      relation to the exact indications and technique for this procedure. Percutaneous
      injection of methylmethacrylate or ethanol may provide marked pain relief or bone
      strengthening in patients, with malignant acetabular destruction, who are unable
      to tolerate surgery. Injection of methylmethacrylate is usually indicated when
      the weight-bearing part of the acetabulum is involved. The goals of treatment are
      pain relief and mechanical strengthening of the acetabulum. Radiography and
      computed tomography must be performed prior to therapeutic percutaneous injection
      to assess the location and extent of the lytic process, the presence of cortical
      destruction or fracture, and the presence of soft-tissue involvement. We report a
      case of a 39-year-old woman with a secondary acetabular lesion, which was treated
      successfully with percutaneous acetabular cementoplasty. We describe a novel
      technique used to inject cement into the lesion, allowing for greater cement
      volume and pressurisation within the lesion.

PMID- 15568427
TI  - Trends in oesophago-gastric surgery in Scotland.
AB  - BACKGROUND: The last twenty years have seen significant changes in both the
      incidence and treatment of gastro-oesophageal disorders as well as a process of
      subspecialisation in general surgery. The aim of this study is to identify the
      changes in gastro-oesophageal surgery in Scotland during this period. METHODS: A
      retrospective analysis of three years of data, taken over a 20-year period (1977,
      1987 and 1997) obtained from the Information and Statistics Division of the
      Scottish National Health Service, examining the number of patients with
      oesophageal cancer, gastric cancer and gastro-oesophageal reflux disease (GORD)
      treated by general and thoracic surgeons. RESULTS: There was a significant
      increase (p=0.001, chi2) in the number of patients with oesophageal cancer (2.52
      fold) and gastric cancer (1.4-fold) treated by general compared with thoracic
      surgeons. Since 1977, the overall operability for oesophageal cancer has remained
      unchanged, while a significant decrease in the overall operability of gastric
      cancer was noted (p<0.001, chi2). There was a 3-fold increase in the incidence of
      GORD with a significant increase (p<0.001, chi2) of those treated surgically.
      Since 1977, there has also been a significant shift of workload from thoracic to
      general surgical units. CONCLUSIONS: Scotland has seen a consistent increase in
      the surgical workload generated by gastro-oesophageal malignancies over the last
      three decades without any improvement in the operability rate. Surgically treated
      GORD has also increased, probably due to the introduction of minimally invasive
      techniques. These trends have implications on healthcare planning, resource
      allocation and surgical training. Appropriate resources and trainees should
      follow the patients to those units carrying out this activity. Further
      centralisation of these services is likely to follow.

PMID- 15568428
TI  - Laboratory research during surgical training.

PMID- 15568429
TI  - Five patients with potentially fatal orofacial infection.

PMID- 15568430
TI  - Ion channels in osteoblasts: a story of two intracellular organelles.
AB  - Recent advances have highlighted a synchronous coordination of osteoblast and
      osteoclast activity, whereby, the osteoblast collates all signals applied to the
      bone and activates osteoclastic resorption. The resorption of the bone and its
      matrix then releases growth factors held within the matrix (bone morphogenetic
      proteins, insulin-like growth factors and transforming growth factors) which then
      stimulate the osteoblast to lay down new osteoid. In healthy adults there is a
      balance between bone deposition and bone loss and there is no net gain or loss,
      and the amount of calcium (Ca2+) ingested in the diet is equal to that which is
      excreted. In the early stages of life, the emphasis is on bone building and more
      Ca2+ is retained from the diet and more bone deposited as the skeleton matures.
      As we age, and, in particular in postmenopausal women, the osteoclastic activity
      outweighs the bone deposition and the patient loses bone becoming osteoporotic.
      The focus of the work reported here was to identify and dissect the various
      cytosolic intracellular signalling pathways within osteoblasts and establish the
      importance of each under different physiological conditions. In brief, two basic
      signalling pathways exist; one is linked with a seven transmembrane spanning
      protein and specific receptors for ligands (the G protein linked pathways) and
      one pathway is linked with protein phosphorylation especially of the tyrosine
      kinases. In general, G protein activity is associated with endocrine ligands such
      as parathyroid hormone (PTH) and (calcitonin has been linked with tyrosine kinase
      activity) tyrosine kinase activity is linked with adhesion of osteoblasts and
      recognition of the substrate to which they are attached. Our specific areas of
      interest are the ways in which Ca2+ activity within the cell is modified and used
      as a signal for further activation and possibly differential gene activation.

PMID- 15568431
TI  - Tissue engineering in surgery.
AB  - The demands for repair and renewal of worn out or injured human tissue continue
      to increase and it is now apparent that this demand cannot be met from human
      donors. A partial solution may be found in living related and trans-species
      transplantation but these approaches invoke the problems of disease transfer and
      ethical dilemmas. Tissue engineering is a new technology that seeks to meet these
      increasing demands by utilising novel cell culture methods in vitro to provide
      tissue replacements in vivo. This article reviews the current state of tissue
      engineering and its potential for use in surgery.

PMID- 15568432
TI  - Anatomy: a must for teaching the next generation.
AB  - Teaching anatomy to both undergraduate medical students and medical graduates is
      in the midst of a downward spiral. The traditional anatomy education based on
      topographical structural anatomy taught by didactic lectures and complete
      dissection of the body with personal tuition, has been replaced by a multiple
      range of special study modules, problem-based workshops, computers, plastic
      models and many other teaching tools. In some centres, dissected cadaver-based
      anatomy is no longer taught. Changing the undergraduate medical curriculum in the
      UK has taken place without any research into the key aspects of knowledge
      necessary or comparing methods of teaching. There is no agreement on a common
      national core curriculum and as a result, numerous new curricula have been
      introduced. No external audit or validation is carried out, so medical schools
      have been free to teach and assess their own work themselves. There is a great
      divergence in medical schools across the UK and Ireland in teaching medicine in
      general and anatomy in particular. Published data on the impact of these changes
      is scant. The reduction in undergraduate teaching and knowledge of anatomy has
      caused great concern, not only for undergraduates but also to postgraduate
      students, especially in surgery. This, together with a change in basic surgical
      training, a marked reduction in demonstrator posts and a change in examination
      standards, has set up a system that is allowing young men and women with a poor
      knowledge of anatomy to become surgeons. There should be a full public debate at
      every level; the Royal Colleges, specialist associations, the Universities,
      Government, both health and education. This debate should highlight areas of
      concern, explore in depth and define a minimal core curriculum for anatomy.
      Teaching must be enhanced with a critical look at both teachers and methods. The
      dominance of research must be reassessed to establish an equitable cohabitation
      with teaching. The place of basic science, especially anatomy in basic surgical
      teaching, must be examined. A thorough knowledge of anatomy should be required in
      the new MRCS-UK. This should be mandatory as a preliminary to higher surgical
      training. The teaching of anatomy in surgical specialities must be improved. Does
      the dissecting room still have a place in educating our under- and postgraduate
      students? Yes--a sound knowledge of anatomy is essential if the medical
      practitioner is going to accurately define and successfully treat the problem
      presented by the patient. The dissected cadaver remains the most powerful means
      of presenting and learning anatomy as a dynamic basis for solving problems. The
      cadaver must not be dismissed as obsolete. Dissection has survived the most
      rigorous test of pedagological fitness--the test of time. The student--cadaver-
      patient encounter is paramount in medical education.

PMID- 15568433
TI  - Syme and his amputation.
AB  - The study examines Syme's indications for and technique of amputation at the
      ankle and reviews the outcome of cases operated on by him for the years 1841
      1866. Sources are the Ward Journals and the General Registers of Patients of the
      Royal Infirmary of Edinburgh for the period under review together with abstracts
      from contemporary medical journals and surgical textbooks. Ninety-eight cases are
      included in the study, of which 87 survived and 11 died in the post-operative
      period. The principal indication for this amputation was 'caries' and the nature
      of this disorder is outlined. Syme's operative technique is described together
      with variations recommended by other contemporary surgeons. Syme introduced
      amputation at the ankle joint with the object of reducing mortality and providing
      a better stump in cases of disease and injury to the foot. The figures from this
      study conclude that he was justified on both counts.

PMID- 15568434
TI  - Mesh plug repair for paraumbilical hernia.
AB  - BACKGROUND: The standard method of repair of paraumbilical hernia (PUH) is by the
      Mayo technique, using a double-breasted flap of the rectus sheath. The
      reproducibility of this technique in the hands of others is highly variable. The
      present study describes and evaluates the application of a Prolene mesh plug in
      the repair of PUH. The use of a mesh plug in hernia repair is not a new concept
      with previous investigators yielding consistently excellent results in the repair
      of femoral and inguinal hernias. METHODS: The study is a retrospective analysis
      of hospital records and telephone interviews of 34 patients having undergone PUH
      repair using the mesh plug technique in the period March 1998- May 2002. There
      were 20 males and 14 females with a median age of 53 years (range 34-86 years).
      Seventy-six percent (26) of the patient sample was obese (median BMI 33).
      Whenever possible local anaesthetic was used. Principal outcome measures studied
      were post-operative complications, recurrences, length of stay in hospital, post
      operative analgesia, duration of drain, return to normal activities and patient
      satisfaction. RESULTS: Post-operative complications encountered included one case
      of seroma and a single wound infection with recurrence. Ninety-seven percent (32)
      of patients were satisfied with the procedure. CONCLUSION: Mesh plug repair can
      be performed with minimal postoperative complications, low recurrence rate,
      minimal post-operative pain and achieving excellent patient satisfaction.
      Prosthetic mesh plug repair under local anaesthetic could become the standard
      treatment for PUH in adults.

PMID- 15568435
TI  - Patients and the Internet: a demographic study of a cohort of orthopaedic out
      patients.
AB  - The Internet is a rich source of medical information but relatively few studies
      have evaluated its use by patients who seek medical information. The purpose of
      this study is to assess the demographics of Internet access and attitudes towards
      the Internet in a cohort of orthopaedic out-patients. Four hundred and three
      patients attending the orthopaedic outpatient fracture clinic completed a
      questionnaire consisting of six divisions including personal information,
      facility to access the Internet and their attitudes towards the information
      retrieved. Fifty per cent of the patients accessed the Internet, either from home
      or office and the maximum usage being in the younger age group. Twenty-nine per
      cent of the patients were aware of the medical information available through the
      Internet. 19% patients would like to have a consultation through the Internet,
      the maximum being in the middle-aged group. 70% of those patients who accessed
      the medical information reported that the Internet information was different than
      that obtained at consultation with the doctor at the out-patient clinic. This
      study reveals that the Internet use by patients is still limited. If an increased
      percentage of medical conditions is to be addressed through the Internet,
      involving patient information, on-line consultations, prescriptions and
      referrals, then a substantial amount of patient education and training is
      required

PMID- 15568436
TI  - Prospective audit of quality of colonoscopy in a surgical coloproctology unit.
AB  - OBJECTIVE: The aim of this study was to prospectively audit the quality of
      colonoscopy and patient acceptance in a Surgical Coloproctology Unit over a one
      year period. PATIENTS AND METHODS: 202 consecutive colonoscopies were evaluated
      over a 12-month period performed by a Consultant, Specialist Registrars and
      Research fellows. Data where recorded for adequacy of bowel preparation,
      completion rate, adequacy of sedation, patient tolerance and duration of the
      procedure. Adequacy of bowel preparation was monitored by scoring bowel content
      and the percentage of bowel wall visualised. Patients completed a questionnaire
      to express their sedation satisfaction, discomfort during the procedure and
      overall satisfaction. RESULTS: The success rate of bowel preparation was 94%.
      Completion rate was 90% in intended full colonoscopies by the Consultant and
      Registrars and 74% by more junior grade endoscopists (overall 86%). The mean dose
      of midazolam and pethidine was higher in patients with unsatisfactory sedation
      than those with satisfactory sedation. The pain score was higher when trainees
      performed the procedure than when performed by the Consultant. Fourteen patients
      refused to undergo the procedure again due to procedure discomfort (n = 7),
      inadequate sedation (n = 2) and bowel preparation discomfort (n = 5). CONCLUSION:
      A high completion rate was achieved, compared with published results. However,
      further improvements are possible especially by improving the performance of
      junior endoscopists and by ensuring optimal bowel preparation. Patients'
      tolerance of colonoscopy was highly acceptable but may also be improved by the
      same methods.

PMID- 15568437
TI  - Hyperplastic polyps and serrated adenomas: colonoscopic surveillance?
AB  - Hyperplastic polyps are not thought to carry a malignant potential. They are,
      therefore, not regularly screened by the majority of clinicians. We present two
      case reports of serrated adenomas that add to a small but expanding body of
      clinical and histological evidence that suggests a hyperplastic to neoplastic
      pathway. Regular colonoscopic surveillance may be indicated in at least some
      cases of hyperplastic polyposis

PMID- 15568438
TI  - Re: Asymptomatic gallstones in the laparoscopic era. JR Coll Surg Edin 2002; 14:
      742-748.

PMID- 15568439
TI  - Re: The early management of severe tibial pilon fractures using a temporary ring
      fixator by Mockford et aL J R Coll Surg Edinb Irel. Apr 2003; 1(2): 104-7.

PMID- 15568440
TI  - Re: Biocompatibility: a biomechanical and biological concept in total hip
      replacement. Surg. J R Coll Surg Edinb Irel. 2003; 1:1-8.

PMID- 15568441
TI  - [Three year action plan to renew Hygiene and Public Health Services (SISP) of
      Local Health Units of Veneto region. Methods and contents].
AB  - The Council of the Veneto Region entrusted the Regional Direction for Prevention
      and the Department for Prevention of ULSS 7 (Local Health and Social Unit) by
      means of the Regional Resolution 3045/2001, the strategic coordination and
      development of a three year Plan concerning the Hygiene and Public Health (SISP)
      Services in Veneto. The Plan aims to renew working methods, areas of activities
      and the organization of the SISP Services. The activities were divided in the
      following four categories from LEA (Essential levels of Assistance) and from the
      regional price list: 1) innovative activities to be put into practice; 2) new
      activities to be developed; 3) activities to be standardized; 4) obsolete
      activities to be deleted. The Plan identified the following five macroareas: 1.
      Epidemiology and prophylaxis of communicable diseases; 2. Prevention of non
      communicable diseases: 3. Urban and Environmental Hygiene; 4. Forensic and
      necroscopic Medicine; 5. Health safeguard in sports activities, with twenty
      specific technical schemes regarding the main areas of Hygiene and Public Health
      Services and three cross cutting schemes regarding: 1. the relationship with the
      user; 2. the SISP System; 3. training. The Plan also identified leaders and
      members of task forces that are in charge of developing the schemes. The 23
      schemes of the Plan were approved by means of the Regional Resolution 3015/2003
      and are now being implemented. The coordination of the activities of the Plan is
      carried out by a special Service.

PMID- 15568442
TI  - [Three year action plan to renew Hygiene and Public Health Services (SISP) of the
      Departments for Prevention of Local Health Units of Veneto region. Specific
      technical and cross cutting schemes--adoption].

PMID- 15568443
TI  - The spectre of HIV/AIDS first emerged and the infection and disease began their
      relentless spread around the world.

PMID- 15568444
TI  - HIV/AIDS in the Eastern Mediterranean: a false immunity?

PMID- 15568445
TI  - Information needs assessment for HIV/AIDS and STIs in the Eastern Mediterranean
      Region.
AB  - We assessed information needs about HIV/AIDS and sexually transmitted infections
      (STI) in the Eastern Mediterranean Region by surveying a sample of people
      considered knowledgeable about the subject. Respondents felt that information on
      certain areas of HIV/AIDS/STIs was much needed. Health care workers were
      perceived to see a high need for information and services generally. Religious
      and community leaders were perceived to see less need for some information and
      services (such as condom promotion, sex education for young people). All groups
      were perceived to see a need for education and services for people living with
      AIDS and drug users. Television and radio were considered the best channels for
      health education while training was seen as the most effective method for
      information exchange.

PMID- 15568446
TI  - Tuberculosis and HIV in the Eastern Mediterranean Region.
AB  - Tuberculosis (TB) is an important public health problem in the Eastern
      Mediterranean Region of the World Health Organization. Every year the disease
      kills 136,000 people and affects 630,000 more. HIV is the most significant risk
      factor for progression from subclinical infection with Mycobacterium tuberculosis
      to active TB. Although the HIV/AIDS threat in the Region appears to be relatively
      modest and so far there has been no evidence of an impact of HIV on TB
      epidemiology in the Region, there is a need to jointly address HIV infection and
      TB more effectively. In this paper the TB situation in the Region and the
      measures being taken to combat it are outlined. The impact of HIV infection on TB
      and the repercussions this could have on theTB situation in the Region are also
      discussed. Actions that are needed to tackle this double burden are suggested.

PMID- 15568447
TI  - Knowledge, attitudes and beliefs about HIV/AIDS in Sana'a, Yemen.
AB  - Although HIV prevalence is low in the Republic of Yemen, existing conditions
      could lead to the rapid spread of HIV/AIDS. Interviewers helped 1033 residents
      aged 14-49 years from randomly chosen households to complete a survey of
      knowledge, attitudes and beliefs about HIV/AIDS. General awareness was good,
      although there were many misconceptions about transmission modes, stigmas and
      discrimination against HIV positive persons. Knowledge was significantly
      determined by schooling, residence and sex. Although they recognized the global
      threat of AIDS, participants underestimated its threat to the Republic of Yemen.
      Television was the commonest source of information. Fostering public awareness is
      recommended to facilitate the development of intervention programmes, fight
      stigmas and ensure delivery of care to those affected.

PMID- 15568448
TI  - Knowledge and attitudes towards AIDS among Saudi and non-Saudi bus drivers.
AB  - We explored the AIDS knowledge and attitudes of long-distance (non-Saudi) and in
      city (Saudi) bus drivers in Saudi Arabia. The 69 non-Saudi drivers tended to
      score higher on knowledge than the 40 Saudi drivers although there were several
      gaps in their knowledge. As regards attitude, more Saudis knew that chastity
      could protect against AIDS and both groups tended to think that they were not the
      kind of people to get AIDS. Intensive health education and follow up is highly
      recommended for this sector of workers.

PMID- 15568449
TI  - Prisoners' knowledge of HIV/AIDS and its prevention in Kerman, Islamic Republic
      of Iran.
AB  - Knowledge of prisoners regarding HIV/AIDS in Kerman was evaluated. Analysis
      indicated that the sample (n = 350) of prisoners had relatively high knowledge
      about HIV/AIDS and its modes of transmission. However, they had a lower level of
      knowledge about HIV/AIDS prevention. The overall knowledge of men about AIDS was
      significantly lower than women. Persons aged 46 years and older and illiterate
      inmates had the least knowledge about modes of transmission. In addition, the
      knowledge of illiterate prisoners about HIV/AIDS prevention was significantly
      lower than others. Evaluation of attitudes and practices of prisoners and
      implementation of educational programmes regarding HIV/AIDS are suggested.

PMID- 15568450
TI  - Knowledge of AIDS and self-efficacy to high-risk sexual practices among Lebanese
      males in New York.
AB  - The relationship of AIDS knowledge and self-efficacy to high-risk sexual
      practices among Lebanese males in NewYork was examined. Self-administered
      questionnaires were completed by a convenience sample. Relationships between AIDS
      knowledge and self-efficacy and high-risk sexual practices for the 25 homosexual
      men were rarely significant, probably because of the small sample. The 261
      heterosexual participants had statistically significant relationships between
      AIDS-knowledge and 9 high-risk sexual practices and between self-efficacy and 18
      high-risk sexual practices. For heterosexuals, and to a lesser degree for
      homosexuals, high-risk sexual practices increased as drug-related behaviours and
      sex with prostitutes increased.

PMID- 15568451
TI  - Human immunodeficiency virus and tuberculosis co-infection in Saudi Arabia.
AB  - Our study determined the rate of screening tuberculosis patients for HIV co
      infection and the HIV seroprevalence among them. We retrospectively reviewed
      medical charts of 437 patients diagnosed with tuberculosis from 1995-2000 in
      Riyadh, Saudi Arabia. Screening was done for 178 (41%) patients: 2 (1.1%) of
      these were found to be HIV positive. Prior to screening, 4 patients were already
      known to be HIV positive. Males were screened more often than females (45% and
      36% respectively). All HIV positive patients were males. Screening was not
      affected by origin of the patient, history of prior tuberculosis or treatment,
      type of tuberculosis involvement or resistance to first line anti-tuberculosis
      agents. In Saudi Arabia, screening for HIV in tuberculosis patients remains
      underutilized. Among screened patients, seropositivity was low.

PMID- 15568452
TI  - Reduction of clinical tuberculosis in HIV-infected males with isoniazid
      prophylaxis.
AB  - Isoniazid (INH) chemoprophylaxis has a positive impact on the development of
      clinical tuberculosis. Due to the increased prevalence of tuberculosis among HIV
      infected individuals, we evaluated the effect of INH on the prevention of
      clinical tuberculosis in HIV-infected patients. We administered 300 mg of INH
      daily to 246 HIV-infected, tuberculin skin test-positive patients for 12 months.
      During 3 years of follow-up, 41 participants died and 94 were lost to follow up.
      Of the 111 patients followed for the 3 years, 12 developed tuberculosis which is
      lower than might be expected in an untreated group. INH prophylaxis appears to be
      an effective method to prevent clinical tuberculosis among HIV-infected,
      tuberculin skin test-positive patients.

PMID- 15568453
TI  - Thrombocytopenia in HIV-infected patients, Islamic Republic of Iran.
AB  - Thrombocytopenia is a blood dyscrasia common in AIDS patients that may result
      from increased viral load and diminished CD4 T lymphocytes. We evaluated the rate
      of thrombocytopenia (platelet count < 100 000/microL) in 170 HIV-infected
      patients (161 males and 9 females) from May 2000-April 2001 in Kermanshah,
      Islamic Republic of Iran. All except 7 females were injecting drug users. While
      34 patients had thrombocytopenia, 3 had severe thrombocytopenia (platelet count <
      20 000/microL). Although prevalence was similar in various stages of HIV
      infection (18.5%-22.5%), severe thrombocytopenia was in patients with CD4 T cell
      count < 200 cells/microL. There were no other associated conditions. Mild
      thrombocytopenia is common in HIV-infected patients in our region.

PMID- 15568454
TI  - Heterosexual awareness and practices among Lebanese male conscripts.
AB  - To assess sexual behaviour and awareness about sexually transmitted infections
      (STIs) among young male adults in Lebanon, and to explore determinants associated
      with increasing levels of sexual risk, a cross-sectional survey of 730 conscripts
      was conducted. About 50% reported any lifetime heterosexual experience. Non
      mutually exclusive sex predominated, and only half of the respondents reported
      consistent condom use during insertive vaginal sex. Higher sexual risk-taking was
      associated with urban residence, higher education, lower family crowding and
      younger age at first sexual experience. A national strategy with epidemiological
      and behavioural surveillance and educational programmes must be initiated before
      sexual risk-taking and incidence of STIs become a major public health issue.

PMID- 15568455
TI  - Risk behaviours associated with urethritis and genital ulcer disease in prison
      inmates, Sindh, Pakistan.
AB  - We evaluated the epidemiological differences with respect to demographics, drug
      use and sexual behaviours associated with lifetime risk of urethritis, genital
      ulcer disease (GUD) and urethritis and GUD together among 3395 male prisoners in
      Sindh. Factors associated with urethritis and GUD alone were sex with multiple
      females, sex with men, and ethnicity. Additional factors associated with
      urethritis alone were sex with prostitutes, sex with partners having multiple
      partners and sex with partners believed to be injecting drugs. Behaviours
      associated with lifetime risk for urethritis and GUD together were sex with
      multiple females, sex with prostitutes, sex with men, sex with partners believed
      to be injecting drugs and ethnicity. These relationships were consistently
      stronger compared to urethritis or GUD alone.

PMID- 15568456
TI  - Knowledge about hepatitis B and C among patients attending family medicine
      clinics in Karachi.
AB  - Knowledge about hepatitis B and C was assessed in a cross-sectional study of 300
      adults aged 18 or older attending family medicine clinics at The Aga Khan
      University Hospital, Karachi. Most knew that hepatitis B and C are viral diseases
      that primarily affect the liver, but knowledge about risk factors for disease
      transmission was poor. Approximately 70% knew that hepatitis B is vaccine
      preventable; 60% had the misconception that hepatitis C is also vaccine
      preventable. The majority incorrectly believed that people with hepatitis B or C
      should follow the diet 'parhaiz'. Generally women knew more than men about the
      diseases. This study suggests that health education about these infections should
      be provided to the public. Family physicians can play an important role in
      educating people about the prevention of these diseases.

PMID- 15568457
TI  - [Urethral discharge in Morocco: prevalence of microorganisms and susceptibility
      of gonococcos].
AB  - We studied 422 patients with urethral discharge recruited from 4 sentinel sites
      in Morocco to determine sociodemographic characteristics, history of STI
      infection, infecting organism and antibiotic susceptibility of Neisseria
      gonorrhoeae. The mean age of the sample was 28 years (range 16-67 years), and
      most were single, had multiple sex partners without taking protective measures
      and came from all social backgrounds; 59.9% had a history of a previous STI. The
      majority (87%) of the infections were the acute form. By polymerase chain
      reaction of urine samples of 399 patients, 41.6% had N. gonorrhoeae infection,
      6.3% Chlamidia trachomatis and 10.8% both organisms; in 41.4% no organism was
      identified. N. gonorrhoeae was strongly susceptible to ciprofloxacin.

PMID- 15568458
TI  - Prevalence of human papillomavirus in Mazandaran Province, Islamic Republic of
      Iran.
AB  - We report the prevalence of human papillomavirus (HPV) types in 100 cervical
      biopsy specimens in Mazandaran province. HPV DNA was detected in 78.6% of
      cervical carcinoma cases, 64.3% of dys/ metaplasia and 9% of normal cases.
      Significant correlation was found between the presence of HPV DNA and development
      of cervical carcinoma. HPV types 16 and 18 were detected in 60.6% of HPV-positive
      cervical carcinoma cases, whereas HPV31 and 33 were found in 21.2%, and HPV6 and
      11 in 18.2%. Among HPV-positive dys/metaplasia cases, 55.6% were positive for
      HPV16 and 18, 22.3% for HPV6 and 11, and 11.1% for HPV31 and 33. Only HPV6 and 11
      were detected in 4 (100%) normal biopsy specimens.

PMID- 15568459
TI  - [Vulvar pathology].
AB  - We evaluated the main causes of vulvar dermatoses; in 785 patients with a vulvar
      diseases who visited Ibn Rochd Hospital Centre, Casablanca between January 1991
      and December 2002. The average age was 31 years (range 2 months to 81 years); 362
      patients (41.52%) had vulvar pruritus, 273 patients (34.77%) had warts and 157
      (20%) had one or more vulva ulcers. The most common infectious pathology was
      papillomavirus infection, found in 273 cases (34.77%), followed by vulvovaginal
      candidiases in 102 cases (12.99 %), syphilitic chancre in 18 cases (2.29%) and
      herpes genitalis in 17 cases (2.16%). The most common non-infectious pathology
      was vulvar dermatosis: 259 cases (32.99%); idiopathic pruritus vulvae: 61 cases
      (7.7%); and tumour-related conditions: 45 cases (5.6%). The frequency of
      infectious conditions was over 50% and these were generally sexually transmitted
      infections.

PMID- 15568460
TI  - Some characteristics of the HIV epidemic in Morocco.
AB  - The first case of AIDS in Morocco was declared in 1986 and since then the number
      of AIDS cases has steadily increased. According to the Ministry of Health, the
      cumulative number of AIDS cases in December 2002 was 1085. HIV in Morocco is
      acquired mainly through heterosexual intercourse. Individuals aged between 30 and
      39 years and in the regions of Marrakech and Agadir have been the most affected.
      Monitoring of the trend of the epidemic by sentinel surveillance surveys
      indicates that Morocco is still a low prevalence zone, since prevalence among
      pregnant women is less than 1%. The estimated number of HIV-infected people in
      Morocco is around 15 000. It is not clear why the epidemic here has not evolved
      as it has in the sub-Saharan countries where it is spreading at an alarming rate.
      Late introduction of HIV-1 subtype B in Morocco, which is relatively less
      transmissible, circumcision and reduced risk behaviours of Muslims may explain
      this. Nonetheless, because prevalence has increased in recent years, unless
      preventive measures are strengthened, the HIV epidemic will worsen in Morocco.

PMID- 15568461
TI  - [Ear, nose and throat pathology in human immunodeficiency virus infection].
AB  - Human immunodeficiency virus (HIV) infection, which is responsible for AIDS, is
      one of the most widespread in the world. Its clinical manifestations are
      polymorphous, and are casued by the virus itself (primary lesions) or the
      resulting immunodepression (secondary lesions). All the body can be affected, and
      the ORL organs are frequently involved. Our purpose was to describe these
      manifestations at all stages of the disease, and to illustrate the importance of
      an early diagnosis, which needs close collaboration between the clinician, the
      anatomopathologist and the radiologist.

PMID- 15568462
TI  - [Parasitic diseases in AIDS in Morocco].

PMID- 15568463
TI  - 3 by 5 initiative: treating 3 million by 2005.

PMID- 15568464
TI  - From the Annual Report of the Regional Director, 2002. Control of sexually
      transmitted diseases (including AIDS).

PMID- 15568465
TI  - Global and regional data on HIV/AIDS/STIs.

PMID- 15568466
TI  - Bibliography of publications on HIV/ AIDS/STIs in Arabic and English.

PMID- 15568467
TI  - [Polybrominated diphenyl ether flame retardants in foodstuffs and human milk].
AB  - Polybrominated diphenyl ethers (PBDEs) have been used worldwide as additive flame
      retardants in polymeric materials. Commercial products consist predominantly of
      deca-, octa-, and pentabromodiphenyl ether mixtures. PBDEs are resistant to
      degradation in the natural environment and Penta-BDE in particular accumulates in
      the fatty tissues of fish, birds and mammals (including humans). Several toxic
      effects on the thyroid system or on neurodevelopment have been reported in
      experimental animals exposed to PBDEs. It is likely that human exposure is
      predominantly through the ingestion of contaminated food and/or mother's milk.
      The potential health effects of dietary exposure to PBDEs have now become a great
      concern because of the increasing PBDE levels in the biosphere. In this review,
      published information on the toxicology of PBDEs, levels in foodstuffs and human
      milk, and analytical methods has been compiled.

PMID- 15568468
TI  - [Detection of genetically modified organisms obtained from food samples ].
AB  - Genetially modified organisms (GMOs) were explored in food samples obtained from
      November 2000 to March 2003 in the Tokyo area by using PCR and real-time PCR
      techniques. The existence of Roundup Ready Soybean (RRS) was surveyed in
      processed foods derived from soybeans, such as tofu, boiled soybean, kinako, nama
      age, abura-age, natto, miso, soymilk and yuba. RRS was detected in 3 of 37 tofu,
      2 of 3 nama-age, 2 of 3 yuba and 3 of 3 abura-age samples. The CBH351 in 70
      processed corn foods, NewLeaf Plus and NewLeaf Y in 50 processed potato foods,
      and 55-1 papaya in 16 papayas were surveyed. These GMOs were not detected among
      the samples. Qualitative and quantitative analyses of RRS and genetically
      modified (GM) corn were performed in soybean, corn and semi-processed corn
      products such as corn meal, corn flour and corn grits. RRS was detected in 42 of
      178 soybean samples, and the amount of RRS in RRS-positive samples was
      determined. The content was in the range of 0.1-1.4% in identity-preserved
      soybeans (non-GMO), and 49.8-78.8% in non-segregated soybeans. On the other hand,
      GM corns were detected in 8 of 26 samples. The amount of GM corn in GM corn
      positive samples was in the range of 0.1-2.0%.

PMID- 15568469
TI  - [Microbiological method for the detection of antibiotic residues in meat using
      mixed-mode, reverse-phase and cation-exchange cartridge].
AB  - A microbiological method for screening of residual benzylpenicillin (PCG),
      oxytetracycline (OTC) and spiramycin (SPM) in meat using a single mixed mode,
      reversed-phase and cation-exchange cartridge was developed. A meat sample was
      extracted with 0.1 mol/mL pH 4.5 phosphate buffer and the extract was applied to
      a MCX cartridge. The cartridge was washed, and adsorbed antibiotic residues were
      eluted with acetonitrile for acidic fractions and acetonitrile containing 5%
      ammonia solution-0.1 mol/mL pH 4.5 phosphate buffer (9:1, v/v) for basic
      fractions. Each eluate was evaporated to dryness and the residue was dissolved in
      phosphate buffer to prepare test solutions for microbiological assay. When the
      diameter of the inhibition zone was more than 12 mm, the result was considered
      positive. In this method, the average recoveries of PCG at 0.05 microg/g, OTC at
      0.1 microg/g and SPM at 0.2 microg/g were 70%, 92% and 84%, respectively.
      Tolerances of the three antibiotics were detected. All the results demonstrate
      that this method is simple, rapid and useful for screening of these three
      antibiotic residues in meat.

PMID- 15568470
TI  - [Determination of mepiquat chloride in grape, wine and juice by liquid
      chromatography with electrospray tandem mass spectrometry].
AB  - A simple and rapid method was developed for the analysis of mepiquat chloride in
      grape, wine and juice by high-performance liquid chromatography with electrospray
      tandem mass spectrometry (LC/MS/MS). Mepiquat chloride was extracted with water
      methanol (1:1). Extracted solution was adjusted to pH 10 with ammonia solution. A
      part of the extracted solution was cleaned up on a styrenedivinylbenzene (SDVB)
      cartridge for LC/MS/MS. The LC separation was performed on a C18 column (50 mm x
      2 mm i.d.) using 0.1% IPCC-MS7-methanol (60:40) as the mobile phase at a flow
      rate of 0.2 mL/min. The mass spectral acquisition was done in the positive ion
      mode by applying selected reaction monitoring (SRM). The recoveries of mepiquat
      chloride from fresh grape, wine and juice fortified at 5 microg/kg and 50
      microg/kg were 84.5-96.1%. The lower limit of quantification was 1 microg/kg.
      Fourteen fresh grape samples, 14 wines (white), 36 wines (red) and 11 juice
      samples were analyzed by this method. Mepiquat chloride was detected in 5 fresh
      grape samples, 3 wines (white) and 1 wine (red) at the level of 12.8-199
      microg/kg, 5.7-47.7 microg/kg and 24.1 microg/kg, respectively.

PMID- 15568471
TI  - [Foods with complaints of fungal contamination and physical problems caused by
      their ingestion].
AB  - A survey concerning foods for which complaints of fungal contamination had been
      made was carried out by distributing and retrieving a questionnaire. The subject
      of the survey was foods that were examined for fungi by institutes and
      laboratories belonging to regulatory agencies following consumers' complaints or
      upon request from food companies to solve problems. We analyzed 1,096 cases
      recovered from 40 organizations located in 30 prefectures. Most foods with fungal
      contamination were "cake and snacks", "beverages" and "bakery products", and
      processed and cooked foods and beverages accounted for more than 90% of the
      complaints. The numbers of cases were greater in the summer and less in the
      winter. The major fungal genus detected in the suspect foods were Penicillium,
      Aspergillus and Cladosporium. Aspergillus niger was the dominant species
      contaminating bakery products. Complainers reported physical symptoms including
      diarrhea, stomach ache, nausea and vomiting in 18% of the cases in which they had
      eaten or drunk fungus-contaminated foods or beverages. There was no clear
      difference in the fungi detected between foods and beverages that caused symptoms
      and those that did not. The proportion of beverages was greater in the foods that
      induced symptoms than in the whole of the foods for which complaints were made.
      This was presumed to be because consumers drank fungus-contaminated beverages
      more often than they ate fungus-contaminated foods.

PMID- 15568472
TI  - [Examination of DNA extract from kernels and processed foods using silica-base
      resin].
AB  - A rapid and simple DNA extraction method is needed to detect genetically modified
      recombinant DNA in soybean kernels and processed foods. However, since various
      kernels and processed foods differ greatly in form, a uniform DNA extraction
      method has proved elusive. The silica-base resin DNA extraction method does not
      use any organic solvent, and the operation is simple and the cost per extraction
      is low, although the frequency of its use is very low and few domestic reports
      exist. We therefore studied suitable conditions for a silica-base resin method.
      We also developed the method to get more pure DNA from soybean kernels. The
      silica-base resin method was found to be adequate for extracting DNA from various
      processed foods for PCR amplification with endogenous gene primers. In the case
      of DNA extraction from soybean kernels, pure DNA could be efficiently extracted
      after pre-heating the soybean suspension in TNE buffer. The extracted DNA showed
      higher ratios of absorption at 260 nm/280 nm and 260 nm/230 nm than those for
      samples obtained with previous methods. Moreover, our observations suggested that
      the extraction time could be reduced to within 30 min for processed foods such as
      tofu.

PMID- 15568473
TI  - [Multiresidue analysis of pesticides in agricultural products by GC-ECD after GPC
      and graphitized carbon column cleanup].
AB  - A multiresidue method that enables determination of many pesticides in
      agricultural products by GC-ECD was studied. First, 63 pesticides were selected
      as agrochemicals commonly used in crop protection in this country, and/or found
      in agricultural products over the past 6 years (April 1996-March 2002) in Aichi
      Prefecture. A sample was extracted with acetonitrile and the acetonitrile layer
      was separated by salting-out. The extract was purified on a GPC system with a
      graphitized carbon columns, and then by a Florisil mini-column fractionation. The
      test solution was subjected to one-injection, dual-column GC with dual ECD
      (column: Stx-CLPesticides and Stx-CLPesticides2). The detection limits of the
      pesticides were in a suitable range (0.0001-0.01 microg/g) for monitoring
      pesticide residues in agricultural products. The method was applied to 203
      commercial agricultural products to demonstrate its suitability for routine
      analysis.

PMID- 15568474
TI  - [Use and regulation of veterinary drugs in Japan and many foreign countries].

PMID- 15568475
TI  - [PCBs in farmed salmon].

PMID- 15568476
TI  - [Establishment of simultaneous determination method of pesticides in foods].

PMID- 15568477
TI  - [Development of sensitive analysis for multiple pesticide residues and monitoring
      data in foods].

PMID- 15568478
TI  - [Paralytic shellfish poison in bivalves collected in Ibaraki, Japan].

PMID- 15568479
TI  - [Myelopathy in patients with antiphospholipid antibodies: clinical features,
      pathogenesis, and review of literature].
AB  - We report 5 patients with anti-cardiolipin IgM-positive myelopathy. The lengths
      of spinal lesions were over two vertebral segments in 4 patients. Four cases
      showed subacute onset, and 2 out of these 4 cases had inflammatory changes in
      cerebrospinal fluid (CSF), and all of their symptoms improved. However, in one
      patient who showed an acute onset and normal findings of CSF, neurological
      symptoms did not improve. Three patients fulfilled the diagnostic criteria of
      primary antiphospholipid antibody syndrome. As for the pathophysiology of
      myelitis associated with antiphospholipid antibodies (aPL), it is suggested that
      vascular thrombosis affecting the blood cord barrier promotes an inflammatory
      changes. The heterogeneous CFS findings seem to reflect the difference in the
      intensity of inflammation. Both vascular thrombosis and inflammatory process
      should be considered as pathogenesis of these patients. Alone or combination
      therapy of steroids and anticoagulants might be effective in patients of
      myelopathy associated with APS.

PMID- 15568480
TI  - [A clinical trial of creatine monohydrate in muscular dystrophy patients].
AB  - To investigate the effects of creatine monohydrate on muscle performance and
      cognitive functions in muscular dystrophy patients, we made an open trial. Twenty
      nine individuals, including 14 myotonic dystrophy (DM), seven facioscapurohumeral
      muscular dystrophy (FSHD), two limb-girdle muscular dystrophy and six healthy
      volunteers, were enrolled in this study and 27 participants completed it. All
      participants took creatine 20g/day for an initial week and 5g/day for successive
      eight weeks. Somatotonic measurements, global subjective assessment, muscle
      performance, cardiopulmonary function, cognitive function, laboratory studies and
      magnetic resonance spectroscopy (MRS) were evaluated at both pre and post
      examination. Subjective improvements were reported from twelve individuals.
      Contrary adverse effects were also complained from ten individuals, although all
      these problems were not serious. Quantitative muscle power was slightly but
      significantly increased in the patients and the number of the patients who failed
      to complete cycle ergometer test was decreased. Phosphocreatine concentrations of
      left calf muscle were not different between pre and post trial examination. No
      obvious changes were detected in cardiopulmonary assessment, cognitive function
      and laboratory date. Creatine has certain expectance for muscular dystrophy
      patients in motor performance. The effect may be achieved not only by increase of
      energy buffer, because clinical improvements were observed in our study
      nevertheless no increase was detected in phosphocreatine concentration. The usage
      of creatine should be managed under medical monitoring since ideal protocol has
      not yet been established and adverse effects can not be ignored.

PMID- 15568481
TI  - [A case of adolescent adrenoleukodystrophy with clinical improvement after
      allogeneic bone marrow transplantation (allo-BMT)].
AB  - We reported a case of adolescent type adrenoleukodystrophy. A 20-year old man
      noticed slight hemiparesis on his right side. After admission, high level of
      serum VCLFA and ACTH and a point mutation in ALDP codon 606 were recognized along
      with white matter lesions in the left medulla, basal ganglia, splenium of the
      corpus callosum on brain MRI. Then we diagnosed the patient as having adolescent
      type adrenoleukodystrophy. We started Lorenzo's oil and seaching for BMT donor.
      Six months later, he received allo-BMT at our hospital. His clinical symptoms
      gradually deteriorated during waiting allo-BMT, and just before allo-BMT, right
      hemiparesis, gait disturbance, exaggerated deep tendon reflexes on his right
      side, right lower quadrantanopia and mild cognitive deterioration. Two months
      after allo-BMT, gait disturbance and right hemiparesis were alleviated. We also
      observed improvement of abnormal findings on brain MRI and magnetic stimulation.
      We believed that allo-BMT is effective for the treatment of adolescent type
      adrenoleukodystrophy.

PMID- 15568482
TI  - [A case of dementia with motor neuron disease associated with agraphia--the
      omission of kana letters].
AB  - We report a 55-year-old right-handed Japanese man with motor neuron disease and
      dysgraphia of kana letters. He was admitted to our hospital because of dysarthria
      and dysphasia. On admission, the results of general physical examination were
      within normal limits. Neurological examination revealed severe dysarthria,
      dysphasia, impaired movement of the tongue without fasciculation and slight
      distal muscle weakness in the bilateral upper limbs. There were no fasciculation
      of the muscle. Deep tendon reflexes were hyperactive without Babinski's signs.
      Sensation, coordination, and gait were normal. Neurophysiological studies
      demonstrated normal motor nerve conduction velocities and sensory action
      potential. The results of needle electromyography of the upper limbs were
      compatible with motor neuron disease (MND). Magnetic resonance imaging (MRI)
      showed atrophy of the bilateral temporal region of the brain. 99mTc-HMPAO SPECT
      (Single Photon Emission Computed Tomography) showed reduced uptake of tracer in
      the bilateral temporal region. On neuropsychological examination, his behavior
      was normal, and orientation and intelligence were also preserved, but his speech
      was severely impaired. Reading comprehension was slightly impaired. In regard to
      writing comprehension, he had no difficulty in copying of words though dictation
      was found to be impaired. He omitted one kana letter in a word. Agraphia is
      accompanied by various factors such as aphasia, dementia, agnosia, alexia. But in
      this case at least for early stage, agraphia existed without other higher
      cortical dysfunction. He did not show severe dementia in his early stage of his
      disease, but developed it later in the disease's progression. In this case,
      agraphia might be due to the atrophic changes in the temporal lobe.

PMID- 15568483
TI  - [A case of cardiac myxoma presenting with multiple cerebellar hemorrhages and
      elevation of interleukin-6 in the cerebrospinal fluid].
AB  - We report a 25-year old man with cardiac myxoma presenting with multiple
      cerebellar hemorrhages and elevation of interleukin-6 (IL-6) in the cerebrospinal
      fluid (CSF). The patient was first admitted to our hospital because of cerebral
      infarctions at the age of 23. After systemic exploration he was diagnosed as
      cardiac myxoma. In this patient, the serum level of IL-6 was elevated. The
      cardiac myxoma was resected and the serum IL-6 level returned to normal. His
      neurological symptoms improved almost to normal and he was discharged. The
      patient had been well for two years until he developed headache at the age of 25.
      Brain MRI revealed multiple cerebellar hemorrhages that overlaid old infarctions.
      The hemorrhages enlarged in a three months period and his headache became worse,
      and then he was admitted again. The IL-6 value was normal in serum at that time,
      but it was elevated in the CSF. The CSF IgG index was also elevated. Cerebral
      angiograms showed no abnormal vessel in the infratentorium, while multiple
      fusiform aneurysms were found in both middle cerebral arteries. A transesophageal
      echocardiography revealed no recurrence of cardiac myxoma. Craniotomy was
      performed and intracerebellar hematomas were removed. Histopathological
      examination showed only old and recent bleedings; no metastatic myxoma tissue was
      found. Although no myxoma tissue was found in biopsy specimen, it seemed
      reasonable that an elevated level of IL-6 in the CSF was due to metastasized
      intracranial myxoma, which caused cerebellar embolism, and then invaded the
      vessel walls and continued to grow. In reviewing the literature we have found no
      reported case of cardiac myxoma with analysis of IL-6 value in the CSF. We
      speculate that the level of IL-6 in the CSF might be a good marker for the
      neurological manifestations of cardiac myxoma.

PMID- 15568484
TI  - [Valproate-induced hyperammonemic encephalopathy in a patient with Sjogren's
      syndrome].
AB  - We describe a 56-year-old woman with hyperammonemic encephalopathy caused by side
      effect of valproic acid (VPA). Ten months before the admission to our hospital,
      she had the first attack of convulsive seizure. Diagnosis of epilepsy was made,
      and the oral administration of VPA (800mg/day) was started at another hospital.
      Seizure was well controlled by VPA, until the recurrence of attack forced her to
      visit our hospital. Convulsive seizure disappeared immediately after intravenous
      administration of diazepam, but consciousness disturbance was prolonged for a few
      days. Since laboratory examinations revealed hyperammonemia without liver
      dysfunction, VPA was discontinued. Subsequently, her consciousness completely
      recovered. Other laboratory findings, including positive antinuclear antibody,
      antibodies to Sjogren's syndrome A, reduced lacrimal secretion in Schirmer's
      test, and cell infiltration in the salivary gland on lip biopsy specimen,
      suggested the presence of Sjogren's syndrome. The hyperammonemia occurs by the
      side effect of VPA, often has basal disease or drug interactions. It was,
      however, especially in patients with basal disease or other drugs, obscure
      whether (and how) Sjogren's syndrome contributed to the development of
      hyperammonemic encephalopathy in this case, since she took only VPA.

PMID- 15568485
TI  - [An autopsy case of systemic vasculitis associated with hepatitis C virus-related
      mixed cryoglobulinemia presenting severe peripheral neuropathy].
AB  - A 75-year-old man, previously diagnosed as having chronic hepatitis C virus (HCV)
      infection, suddenly developed left foot drop, followed by progressive motor
      weakness and sensory disturbance in all of the extremities. Because of an
      elevated level of the rheumatoid factor (RF), he had been treated with
      antirheumatic drugs three years before the onset of his neurological symptoms.
      Within two months, he became unable to walk any more, and was transferred to our
      hospital. Neurologic examination showed asymmetrical severe muscular weakness and
      atrophy of all the limbs, and a sensory deficit under the level of the wrists and
      knees. Livedo reticularis was also noted in bilateral legs. Nerve conduction
      study revealed severe sensorimotor axonal neuropathy, and muscle biopsy specimens
      showed necrotizing vasculitis of small arteries in the perimysium. Serological
      tests indicated type II cryoglobulinemia (monoclonal IgAkappa + polyclonal IgG).
      A diagnosis of vasculitic neuropathy associated with HCV-related mixed
      cryoglobulinemia was made. A high-dose intravenous immunoglobulin therapy (IVIg)
      and a high-dose steroid therapy were not effective, and he died of alveolar
      hemorrhage probably due to pulmonary vasculitis. Postmortem pathological
      examination revealed severe vasculitis, accompanied by fibrinoid degeneration and
      the infiltration of predominant mononuclear cells into the small and medium-sized
      vascular walls of multiple organs such as the liver, kidney, pancreas and
      intestine as well as the peripheral nerves and skeletal muscles. A severe loss of
      myelinated fibers were also observed in the multiple peripheral nerves examined.
      We emphasize that patients with HCV infection and mixed cryoglobulinemia may
      develop severe systemic vasculitis resembling polyarteritis nodosa leading to
      often life-threatening polyvisceral failure, particularly in patients showing
      progressive mononeuropathy multiplex.

PMID- 15568486
TI  - [Allergic skin rashes by methylprednisolone in a case with multiple sclerosis].
AB  - We reported a 34-year-old woman with multiple sclerosis showing an allergic
      reaction to methylprednisolone sodium succinate. She was admitted to our hospital
      with a complaint of hypesthesia in the right side of the face and body. MRI
      showed several high signal intensity lesions in her brain with Gd-DTPA
      enhancement effect. She was diagnosed as having an acute relapse of MS from
      previous episodes and clinical findings. We started a methylprednisolone pulse
      therapy. After the injection on the first day, skin rashes appeared on her trunk
      and thigh. On the second day, the skin rashes spread over her whole body. Patch
      test for methylprednisolone sodium succinate (MP) was positive. The steroid
      administration was substituted by intravenous injections of betamethasone
      100mg/day for three days. Her neurological and radiological findings were
      successfully disappeared without any side effects. This case indicates the
      efficacy of substitution therapy of betamethasone for MP.

PMID- 15568487
TI  - [Erythrocyte from Duchenne muscular dystrophy is fragile].
AB  - Intermittent indirect hyperbilirubinemia was occasionally observed in Duchenne
      muscular dystrophy (DMD) patients. We suspected that hyperbilirubinemia might be
      caused by hemolysis of fragile erythrocytes due to damaged endothelium, which was
      reported in DMD. To examine the fragility of erythrocytes, we performed osmotic
      resistance test in 25 DMD, 12 myotonic dystrophy (DM), 12 amyotrophic lateral
      sclerosis (ALS) and 24 healthy volunteers (male 15, female 9). Minimum resistance
      (beginning point of hemolysis) of DMD (0.447 +/- 0.016%) was higher than that of
      age matched male controls (0.425 +/- 0.018%: p = 0.0008) and that of DM (0.440 +/
      0.015%) was also higher than that of total controls (0.423 +/- 0.016%, p =
      0.0077). The number of poikilocytes was increased in DMD (35.45 +/- 41.17 per a
      high magnitude field), however no obvious correlation was detected between the
      ratio of poikilocytes and resistances. Total bilirubin showed correlation (p =
      0.029) to minimum resistance. These findings suggested that erythrocyte membrane
      is fragile in DMD. Involvement of endothelial damage could not be proven, because
      all investigated patients showed normal tissue plasminogen activator inhibitor-1.
      Although the mechanism of fragile erythrocytes in DMD is still unknown, we should
      pay attention to interpret bilirubin in DMD, because hemolysis due to erythrocyte
      fragility may influence the value.

PMID- 15568488
TI  - [A patient with distal muscular dystrophy without mutations in dysferlin gene but
      with abnormal dysferlin localization in muscle fibers].
AB  - We report a 40-year-old man who noticed difficulty in standing on his tiptoe from
      approximately 36 years-old. He presented with selective calf muscle weakness on
      flexion. The serum creatine kinase (CK) level slightly increased to 569IU/l.
      Muscle computed tomography (CT) revealed selective gastrocnemius and soleus
      muscle atrophy with fat tissue replacement. A biopsy of the left gastrocnemius
      muscle revealed a marked variation in muscle fiber size and some necrotic and
      regenerating fibers. Immunohistochemical analysis using an anti-dysferlin
      antibody showed a faint and irregular immunostaining of the muscle surface
      membrane and abnormal immunoreactive depositions in the cytoplasm, although
      normal dysferlin content was detected by Western blotting. The sequence analysis
      of all exons of the dysferlin gene revealed no responsible mutations. The case
      had clinical and pathological findings similar to those of Miyoshi myopathy. The
      present study indicates that there may be a secondary abonormality of dysferlin
      derived from some other factors in patients with clinical and pathological
      findings similar to those of Miyoshi myopathy. The mechanism of dysferlin
      expression should be elucidated to obtain a conclusive pathogenetic mechanism
      underlying this disorder.

PMID- 15568489
TI  - [Bradykinetic utterances and monopitch speech in patients with Parkinson's
      disease].
AB  - We compared vocalization and speech of 20 patients with Parkinson's disease with
      those of 24 healthy volunteers using acoustic analysis. The time from the
      beginning of pronunciation of "a" to the maximum amplitude was significantly
      longer in the Parkinson group than in the healthy group. In a reading aloud test
      using a short sentence "o-te-ra-ni-o-ba-ke-ga-de-ta (a ghost appeared in a
      temple)", the coefficient of variation of the mean fundamental frequency for each
      syllable was significantly smaller in the Parkinson group. In addition, the
      Parkinson group showed few changes in the fundamental frequency of the each
      syllable through the whole sentence, which was spoken in a monopitch pattern.
      However, there were no differences between the Parkinson group and the healthy
      volunteers in the time that each syllable was sustained and in the length of
      syllables. These results suggest that patients with Parkinson's disease have
      bradykinetic utterance. In reading aloud the short sentence, the tone of each
      syllable was flat and the speech was monopitch lack articulation. The saccadic
      eye movements of 15 of the patients with Parkinson's disease were recorded using
      an electrooculogram in order to evaluate the correlation with bradykinetic
      utterances. Although monopitch speech and bradykinetic utterances were
      correlated, the bradykinetic saccadic eye movements and bradykinetic utterances
      were not correlated.

PMID- 15568490
TI  - [Megadolichobasilar artery and neurogenic hypertension].

PMID- 15568491
TI  - [Dose levodopa decrease the right and left difference of the striatal blood flow
      in patients with hemiparkinsonism?].

PMID- 15568492
TI  - Escherichia coli O157:H7 outbreak at a summer hockey camp, Sudbury 2004.

PMID- 15568493
TI  - Revised WHO drinking-water guidelines to help prevent water-related outbreaks and
      disease.

PMID- 15568494
TI  - [Cell technologies and modern medicine].

PMID- 15568495
TI  - [Endogenic opioid peptides and antiarrhythmic effect of adaptation to stress].
AB  - Adaptation of rats to repeated short-term immobilization increases cardiac
      resistance to an arrhythmogenic action of coronary artery occlusion (10 min) and
      reperfusion (10 min) in rats anesthetized with ketamine and artificially
      ventilated. We examined the role of opioid receptors and endogenous opioid
      peptides in the development of this antiarrhythmic effect produced in response to
      repeated periods of immobilization stress. We found that repeated daily stress
      during a 15-day period resulted in an increase of leu-enkephalin in blood plasma,
      in the suprarenal gland and myocardium. Adaptation to stress also resulted in an
      increase in beta-endorphinl-31 in blood plasma, the hypophysis, hypothalamus and
      midbrain. Pretreatment with selective mu, delta and cappa opioid receptor (OR)
      antagonists had no effect on the incidence of occlusion and reperfusion-induced
      arrhythmias in non-adapted control rats. However, pretreatment with the selective
      muOR antagonist CTAP (0.5 mg/kg) intravenously completely abrogated the
      antiarrhythmic effect of adaptation. Selective delta and cappa receptor
      antagonists did not affect the antiarrhythmic effect of adaptation. Prior
      administration of the selective muOR agonist DALDA (0.1 mg/kg) decreased the
      incidence of occlusion and reperfusion-evoked arrhythmias in non-adapted rats.
      This effect was abolished by pretreatment with the selective muOR antagonist CTAP
      (0.5 mg/kg). These data suggest that mu opioid receptors and endogenous opioid
      peptides play an important role in the antiarrhythmic effect of adaptation to
      stress in rats.

PMID- 15568496
TI  - [Correlation between some stress-realizing and stress-limiting systems in an
      acute period of ischemic stroke].
AB  - Concentrations of stimulating (glutamate, aspartate) and inhibitory (GAMK,
      glycin) amino acids were measured in cerebrospinal liquid of 67 patients with
      ischemic stroke. The condition of stress-realising and stress-limiting systems
      (SRS and SLS) was assessed by dynamics of stimulating and inhibitory amino acids.
      High and rapidly increasing concentration of glutamate within the first 24 h of
      the disease predicts a poor prognosis. Early rise of GAMK concentration is a
      favourable and reliable prognostic sign. Hyperactivation of glutamatergic system
      and deficiency of inhibitory GAMK-ergic system cause imbalance between mediators
      and metabolites of SRS and SLS. The severity and duration of this imbalance
      determine severity of clinical symptoms and outcome of the disease.

PMID- 15568497
TI  - [Effects of endotoxin of gram-negative intestinal microflora on adaptation to
      physical exercise].
AB  - The study of plasm concentration of endotoxin (ET), activity of antiendotoxinic
      immunity (AEI) and early adaptation to exercise in 61 athletes and 13 students
      who were not athletes has revealed correlation between the former two and the
      latter parameters. ET was elevated in all the examinees prior to exercise. In
      exercise maladaptation both athletes and non-athletes demonstrated high ET levels
      in blood plasm and low AEI. It is suggested that ET may have a negative effect on
      exercise adaptation. Elevation of lipopolysaccharide concentration in systemic
      blood flow and depressed AEI may provoke acute maladaptation after exercise.

PMID- 15568498
TI  - [Some pathophysiological mechanisms of muscular tone impairment].
AB  - Pathophysiological mechanisms of the muscular tone was studied
      clinicoelectrophysiologically (the method of stimulating electromyography with
      evoked H-reflex) in 130 healthy subjects and 63 patients with dystonia musculorum
      deformans (23 patients of the latter were examined before and after intake of a
      therapeutic dose of L-DOPA). It was found that patients with impaired muscular
      tone have low activity of spinal motoneurons on both sides of the body especially
      the activity of phasic motoneurons and on the right side of the body. L-DOPA
      activates motoneurons, higher activation seen for the phasic motoneurons and on
      the right side of the body.

PMID- 15568499
TI  - [The role of the nervous factor in regulation of oxygen supply to the small
      intestine].
AB  - The experimental model of rat bilateral subdiaphragmatic stem vagotomy was used
      to study the role of parasympathetic nervous system in regulation of circulation
      and oxygen supply to the small intestine. Cut of the vagus nerves is shown to
      cause redistribution of the blood flow between gastroduodenal organs, to slow
      down local circulation, to reduce oxygen tension in the muscular lining of the
      jejunum, to raise water content in the wall and change magnetorelaxational
      characteristics. Morphologically this manifested in altered arteriolar and
      capillary configuration, dilation of the capacity microvessels, dystrophia of
      microvessel wall, red cell aggregation in capillaries and venules, defective
      permeability of the vascular wall. The above indices changed most 7 and 30 days
      after vagotomy. It is evident that impaired vagus innervation produces secondary
      circulation hypoxia in the small intestine.

PMID- 15568500
TI  - [Effect of magnetolaser therapy on dynamics of bioamines, heparin in injured
      peritoneum and healing of this injury].
AB  - An experimental study on 62 guinea pigs was made to examine a magnetic-laser
      effect on the levels of histamin, serotonin, catecholamine, heparin and
      pathomorphology of wound healing after operations in the abdominal cavity.
      Magnetolaser therapy promotes fast normalization of the above levels, suppression
      of inflammatory-necrotic processes and stimulation of reparative and regenerative
      processes.

PMID- 15568501
TI  - [Erythrodieresis in nitrite intoxication of varying duration in rats].
AB  - We studied cellular mechanisms of erythrophagocytosis on day 3, 7, 14 and 21
      after sodium nitrite administration in a dose 0.2 g/l using the technique of
      peritoneal macrophages and autologous erythrocytes cultivation. At any terms of
      the experiment erythrophagocytosis activation was observed, the number of
      macrophages, adhering erythrocytes and macrophages with phagosomes and hemoglobin
      inclusions was increased.

PMID- 15568502
TI  - [Systemic enzyme therapy of experimental gout glomerulonephritis].
AB  - Renal lesion deteriorates the course and prognosis of gouty glomerulonephritis.
      Current pathogenetic therapy is not sufficiently effective. Effects of different
      treatments on morphological and functional manifestations of renal disorders in
      experimental gouty glomerulonephritis are reviewed.

PMID- 15568503
TI  - [Determination of the efficiency of registration of X-ray diagnostic systems by
      visually detected minimal radiation contrast].
AB  - Described in the paper is a relatively simple method for the determination of the
      efficiency of registration of X-ray diagnostic systems by the whole tract of
      transformation of radiation contrast from the spot of contrast-sensitivity test
      to the visual registration of image. It is just enough to have the contrast
      sensitivity test and to measure the dose at test location. On the basis of the
      visually registered minimal contrast the efficiency of registration of a
      diagnostic system is evaluated by the radiation-contrast parameter. The suggested
      method can be used at handover tests and in testing the X-ray systems during
      their exploitation.

PMID- 15568504
TI  - [A study of parameters of scanning roentgenographic systems].
AB  - The paper presents the study results related with operational properties of
      digital X-ray diagnostic systems designed on the basis of silicon detectors.
      Suggestions are defined for the use of evaluation methods applicable to image
      parameters with respect to the properties of an examined object.

PMID- 15568505
TI  - [Specrozonal X-ray detector and determination of the efficient atomic number of
      absorbing tissue].
AB  - A method is described for determining the efficient atomic number of inclusion
      tissue substance, visualized in image, by the characteristic angle estimated by
      means of spectronazal X-ray detector. Described are study results of the
      influence of inclusion's geometric dimensions and of the whole radiation
      filtration exerted on the value of characteristic angles for different
      substances. The experimental values of effective atomic numbers are shown to fit
      well, within the range limited by radiation contrast, the theoretical ones.

PMID- 15568506
TI  - [Correlation of noises in the channels of digital X-ray receiver-transformer and
      the evaluation of registration's quant efficiency].
AB  - Theoretical and experimental research results related with the influence of
      correlation of signals in neighboring elements of digital X-ray receiver
      transformer produced on the evaluation of the output ratio noise/signal and, as a
      consequence, on the evaluation of quantum registration efficiency are described
      in the paper.

PMID- 15568507
TI  - [Limiting resolution of X-ray computer tomography in examination of man].
AB  - It is shown as necessary to increase the intensity of radiation source by at
      least 20 times in order to ensure a 2-fold enhancement of resolution. It
      predetermines the permissible values of dose per object, which in their turn,
      condition the permissible values of quantum noise per image (tomogram) as well
      space and density resolutions. The dose, when intensified purposefully in order
      to enhance the tomography image resolution, is apparently a limitation for
      examination of man by X-ray computer tomography.

PMID- 15568508
TI  - [Determination of total filtration and half attenuation layer in X-ray diagnostic
      units by relative radiation output].
AB  - Described is a relatively simple technique applicable to estimating the
      independent and additional filtration of X-ray images by the relative radiation
      output with a voltage generation range of 50 to 120 kB. It is shown as possible
      to determine the half-attenuation first layer in its aluminum equivalent and
      without using any aluminum filters. The suggested technique can be used in turn
      over and regular tests of medical X-ray units as well as in their exploitation.

PMID- 15568509
TI  - [Estimated equivalent radiation conditions (EERC), more useful clinical data and
      estimation of potential resorption of lesion nodule with respect to its volume
      and total focal dose].
AB  - Assumptions on properties of tumor cells are defined. On the basis on them the
      survival rate of tumor cells is described by the LQ function and the dependence
      of resorption probability (RP) in the lesion nodule on the number survived tumor
      cells (tumor volume) and on the total focal dose (TFD) is described by the
      Poisson function. An analysis of the above approach to the determination of
      lesion-nodule RP resulted in designing a calculation method for EERC that can be
      used to estimate the lesion-nodule RP as a function of its volume and TFD. An
      analytical or graphical description of the RP/TFD dependence for a fixed volume
      of lesion nodule is needed for the implementation of EERC. There is no need to
      determine the cell structure of tissue or the radiobiological properties of its
      cells. The possibility to construct the RP section function and to extend, thus,
      the volume of useful clinical data belongs to the method's advantages.

PMID- 15568510
TI  - [Digital X-ray equipment presented at the "Healthcare-2003" exhibition].
AB  - Published data on equipment for X-ray filming, fluorography, mammography and for
      automated developing machines, which were displayed at the "Healthcare-2003"
      exhibition, Moscow, are surveyed in the paper.

PMID- 15568511
TI  - [Evolution of X-ray image receivers].
AB  - The evolution of X-ray image receivers of X-ray radiation for roentgenoscopy and
      roentgenography was analyzed for the period of the last century; prospects for
      the future are made.

PMID- 15568512
TI  - [An analysis of X-ray diagnostic equipment at Moscow prevention and patient-care
      facilities].
AB  - The paper contains the results of an analytical study held, 2001-2003, at
      prevention and patient-care facilities of Moscow and dedicated to classification
      of their X-ray diagnostic equipment (XDE) by models. On the basis of an analysis
      of typical XDE failures the methodological recommendations for the XDE technical
      expertise are defined that enable the possibility to evaluate objectively the
      serviceability of equipment after appropriate repair and to extend its
      exploitation time over several years without any noticeable worsening in X-ray
      diagnostics or radiation safety.

PMID- 15568513
TI  - [Monitoring of dose loads of patients in mammography].
AB  - Dosimetric data obtained experimentally and needed in calculating the efficient
      irradiation doses applicable to patients in film mammography are elucidated in
      the paper. The values of individual effective doses are defined with respect to
      the sizes of the mammary gland, regimes of X-ray examinations and sensitivity of
      the "screen-film" system. Recommendations are provided for choosing the optimal
      regimes ensuring high-quality images and for minimal dose loads of patients'
      irradiation.

PMID- 15568514
TI  - [Digital fluorograph with automatic exposition].
AB  - Discussed in the paper is a system of automatic exposition choice in a digital
      fluorograph designed by the "Gelpik" company, Moscow. The perspective equipment
      variation is as follows: intensifying screen + optic system + charge
      communication device-matrix.

PMID- 15568515
TI  - [Digital X-ray unit ARC-01-"OKO"].
AB  - Presented is a description of a new roentgenographic unit ARC-01-"OKO" designed
      by the "Electron" Research and Design Company Ltd. for digital roentgenography
      (with X-ray transparent deck) of patients in the standing, sitting and lying
      positions. The unit enhances the capacity of X-ray examination room and makes
      almost unnecessary the use of X-ray films and chemicals. According to its
      medicals trials, the structural elements of the thorax, lungs, mediastinum,
      diaphragm, skull, lower and upper extremities, vertebral column, abdominal cavity
      and pelvis, when examined in different projections, are reproduced by the unit
      with good and excellent quality both at health and disease.

PMID- 15568516
TI  - [Compact X-ray multimeter with mobile computer].
AB  - There is a description of a multifunctional portable unit designed for
      measurement of anode voltage at the X-ray tube, capacity of exposition dose and
      of exposition time (i.e. of X-ray diagnostic parameters).

PMID- 15568517
TI  - [A new small-dose digital fluorograph, ProScan-7000].
AB  - There is a description of a new digital fluorograph designed at "Roentgenoprom"
      Ltd. Co., Moscow. A specially constructed linear detector and new soft are used
      in it, which essentially enhances the image quality.

PMID- 15568518
TI  - Repair of defects in articular joints. Prospects for material-based solutions in
      tissue engineering.

PMID- 15568519
TI  - Rotational malalignment after fractures of the femur.

PMID- 15568520
TI  - Searching the internet for orthopaedic knowledge.

PMID- 15568521
TI  - Radiological changes in second- and third-generation Zweymuller stems.
AB  - The Alloclassic and Endoplus femoral stems have the same grit-blasted surface and
      are hot forged from the same titanium alloy. Only the external form of the
      implants differs slightly. It was our aim to examine the differences in
      radiographic bone response between the Alloclassic (second generation) and the
      Endoplus (third generation) femoral stems. We compared 79 prostheses in 70
      matched patients studied over a minimum of two years. Radiolucent lines, adaptive
      bone remodelling, subsidence, heterotopic bone formation and lysis were recorded
      in the Gruen zones. Radiolucencies were mainly found in zones 1 and 7 but to a
      greater extent in the Endoplus than in the Alloclassic group (p < 0.001 in zone
      1, p < 0.05 in zone 7). We found lucent lines in three or more Gruen zones in
      seven patients all of whom were in the Endoplus group (p < 0.05). Zones 2 and 6
      had a significantly higher rate of lucencies in the Endoplus group (p < 0.001).
      We encountered a combination of proximal lucent lines in zones 1 and 7 with
      distal hypertrophy of the cortical bone in zones 2, 3, 5 and 6 in eight patients,
      all from the Endoplus group (p < 0.05). In other patients bone atrophy (stress
      shielding) in zones 2 and 6 was seen more frequently in the Endoplus than in the
      Alloclassic group (p < 0.001). In neither group was there radiological evidence
      of osteolysis. Heterotopic bone formation and subsidence occurred with similar
      frequency in both groups. Our study shows that a small change in the form of the
      femoral implant can result in statistically significant radiological changes in
      bone remodelling. Whether this will result in clinical compromise is unknown.
      However, it seems likely that the Endoplus femoral stem will perform differently
      from the Alloclassic.

PMID- 15568522
TI  - Is epidural anaesthesia acceptable at total hip arthroplasty? A study of the
      rates of urinary catheterisation.
AB  - Epidural anaesthesia, with and without opiate, is widely used in total hip
      arthroplasty (THA). It may cause urinary retention, leading to catheterisation,
      and a subsequent increase in the likelihood of deep infection. We investigated
      prospectively the rate of urinary catheterisation in patients after THA performed
      under general anaesthesia, with or without peri-operative fentanyl and
      bupivacaine opiate epidural anaesthesia. Of 173 patients, 75 received general
      anaesthesia alone and 98 both general and epidural management. The post-operative
      rate of catheterisation was 14.7% in those who received general anaesthesia alone
      and 13.3% in those who received both. Our findings suggest that the rate of post
      operative urinary catheterisation does not increase when general anaesthesia is
      supplemented by epidural anaesthesia using fentanyl and bupivicaine.

PMID- 15568523
TI  - Hydroxyapatite ceramic-coated femoral stems in young patients. A prospective ten
      year study.
AB  - We describe the clinical and radiological results of 38 total hip replacements
      (THR) using the JRI Furlong hydroxyapatite-ceramic (HAC)-coated femoral component
      in patients younger than 50 years. The mean age at the time of operation was 42
      years (22 to 49) and the mean length of follow-up was ten years (63 to 170
      months). All patients receiving a Furlong HAC THR were entered into the study
      regardless of the primary pathology including patients who had undergone previous
      hip surgery. The mean Harris hip score improved from 44 before operation to 92 at
      the last post-operative review. After 12 years the cumulative surivival for the
      stem was 100% (95% confidence interval 89 to 100). No femoral component was
      revised. Our results show that the Furlong HAC implant gives excellent long-term
      results in young patients with high demands.

PMID- 15568524
TI  - Impaction femoral allografting and cemented revision for periprosthetic femoral
      fractures.
AB  - We reviewed retrospectively the outcome of the treatment by impaction grafting of
      periprosthetic femoral fractures around loose stems in 106 patients with
      Vancouver type-B2 and type-B3 fractures. Eighty-nine patients had a cemented
      revision with impaction grafting and a long or short stem. The remaining 17 had
      cemented revision without impaction grafting. Fractures treated by impaction
      grafting and a long stem were more than five times likely to unite than those
      treated by impaction grafting and a short stem (odds ratio = 5.5, 95% confidence
      interval (CI) 1.54 to 19.6; p = 0.009). Furthermore, those with impaction
      grafting and a long stem were significantly more likely to unite than those with
      a long stem without impaction grafting (odds ratio = 4.07, 95% CI 1.10 to 15.0; p
      = 0.035). There was also a trend towards a higher rate of union in those treated
      by impaction grafting than in those without (odds ratio = 2.69, 95% CI 0.86 to
      8.45; p = 0.090). Impaction grafting is being increasingly widely used for the
      restoration of femoral bone stock. It can be successfully applied to
      periprosthetic femoral fractures but a long stem should be used to bypass the
      distal fracture line.

PMID- 15568525
TI  - The flexion gap in normal knees. An MRI study.
AB  - Varus and valgus joint laxity of the normal living knee in flexion was assessed
      using MRI. Twenty knees were flexed to 90 degrees and were imaged in neutral and
      under a varus-valgus stress in an open MRI system. The configuration of the
      tibiofemoral joint gap was studied in slices which crossed the epicondyles of the
      femur. When a varus stress was applied, the lateral joint gap opened by 6.7 +/-
      1.9 mm (mean +/- SD; 2.1 to 9.2) whereas the medial joint gap opened by only by a
      mean of 2.1 +/- 1.1 mm (0.2 to 4.2). These discrepancies indicate that the
      tibiofemoral flexion gap in the normal knee is not rectangular and that the
      lateral joint gap is significantly lax. These results may be useful for adequate
      soft-tissue balancing and bone resection in total knee arthroplasty and
      reconstruction surgery on ligaments.

PMID- 15568526
TI  - Two mechanical devices for prophylaxis of thromboembolism after total knee
      arthroplasty. A prospective, randomised study.
AB  - The optimal characteristics of pneumatic compression for mechanical prophylaxis
      of thromboembolism after total knee arthroplasty (TKA) are not known. Our study
      compared two methods of calf compression, with the hypothesis that the device
      which provided a larger increase in peak venous velocity would produce a lower
      rate of thromboembolism. We performed a prospective, randomised study on 423
      patients (472 knees). Duplex ultrasonography was carried out by experienced
      technicians who were blinded to the device used. Overall, 206 patients (232
      knees) used a rapid inflation, asymmetrical compression (RIAC) device and 217
      (240 knees) a sequential circumferential compression device (SCD). The rate of
      venous thromboembolism was 6.9% with the RIAC device compared with 15% for the
      SCD device (p = 0.007). The incidence of thrombi with unilateral primary TKA was
      8.4% for the RIAC compared with 16.8% for the SCD device (p = 0.03). In 47
      patients with a bilateral TKA, the incidence of thrombi was 4% for the RIAC
      compared with 22.7% for the SCD device (p = 0.05 per knee). There was a low rate
      of mortality and pulmonary embolism when using mechanical prophylaxis for
      thromboembolism after TKA. Our findings show that the use of rapid inflation,
      asymmetrical calf compression gave a significantly lower rate of thromboembolism.

PMID- 15568527
TI  - Fractures of the calcaneum. A review of 70 patients.
AB  - We have assessed the long-term results after operative and non-operative
      treatment of undisplaced and displaced calcaneal fractures. At a mean of 6.5
      years, we reviewed 70 patients with a calcaneal fracture who were divided into
      four groups: group 1, 18 patients with undisplaced fractures and a normal
      Bohler's angle (BA) who had been treated non-operatively; group 2, 23 with intra
      articular fractures and a BA < 10 degrees who had been treated non-operatively;
      group 3, 13 with intra-articular fractures and a BA > 10 degrees who had been
      treated surgically; and group 4, 16 with intra-articular fractures and a BA < 10
      degrees who had been treated surgically. The results were assessed by a clinical
      score considering pain, return to work, return to physical activity, change in
      shoe-wear and the requirement for subtalar arthrodesis. Patients with undisplaced
      calcaneal fractures had a good outcome. Those with displaced fractures treated
      surgically who presented at follow-up with a BA > 10 degrees had a satisfactory
      functional outcome and those with displaced fractures who had non-operative
      treatment had a poor outcome. The poorest outcome was consistently seen in
      patients who were treated operatively without restoration of BA. Open reduction
      and internal fixation of intra-articular calcaneal fractures can only be expected
      to benefit those patients in whom nearly anatomical reconstruction is obtained.

PMID- 15568528
TI  - Factors associated with nonunion in conservatively-treated type-II fractures of
      the odontoid process.
AB  - In type-II fractures of the odontoid process, the treatment is either
      conservative in a halo vest or primary surgical stabilisation. Since nonunion,
      requiring prolonged immobilisation or late surgery, is common in patients treated
      in a halo vest, the identification of those in whom this treatment is likely to
      fail is important. We reviewed the data of 69 patients with acute type-II
      fractures of the odontoid process treated in a halo vest. The mean follow-up was
      12 months. Conservative treatment was successful, resulting in bony union in 32
      (46%) patients. Anterior dislocation, gender and age were unrelated to nonunion.
      However, nonunion did correlate with a fracture gap (> 1 mm), posterior
      displacement (> 5 mm), delayed start of treatment (> 4 days) and posterior
      redisplacement (> 2 mm). We conclude that patients presenting with these risk
      factors are unlikely to achieve bony union by treatment in a halo vest. They
      deserve careful attention during the follow-up period and should also be
      considered as candidates for primary surgical stabilisation.

PMID- 15568529
TI  - Epidemiology of femoral fractures in children in the West Midlands region of
      England 1991 to 2001.
AB  - We have attempted to describe the epidemiology of femoral fractures in children
      in the West Midlands region of the National Health Service in England. Our source
      of data was the Regional Hospital Episode Statistics database for the years 1991
      2 to 2001-2. Cases were defined as emergency hospital admissions in patients aged
      under 16 years, with a diagnostic code of femoral fractures in any field, and
      resident in the West Midlands. Between 1991-2 and 2001-2, 3272 children aged
      under 16 years with femoral fractures were admitted to hospital. The crude
      incidence during this period decreased from 0.33 to 0.22 femoral
      fractures/1000/year. Those caused by traffic accidents decreased by 43%, and by
      falls by 29%. The peak age-gender-specific incidence (0.91/1000/year) was in two
      year-old boys, and this was 50% higher than in the next highest age-gender group.
      In the first year of life, the incidence in boys and girls was the same.
      Thereafter the rate in boys exceeded that in girls, varying from 1.6 times at 11
      years to 4.7 times at 14 years. Falls accounted for 49% of the fractures, varying
      from 77% in one-year-olds to 26% in eight-year-old children. Traffic accidents
      were responsible for 26% of fractures varying from 55% in ten-year-old to 2% in
      one-year-old children. Maltreatment was recorded in 1.3% of all cases, and in
      8.5% of children under one year. Twice as many fractures were seen in May to
      August than in January (winter). The rates of fractures were associated with
      deprivation for all age-gender groups. Fractures of the shaft accounted for 58%
      of all fractures, varying from 70% in three-year-old to 34% in 13-year-old
      children. Our findings show that there has been a decrease in the incidence of
      femoral fractures during the 1990s and early 2000s. Two-year-old boys had twice
      the rate than any other single-year age-gender group. More deprived areas had
      much higher rates which suggests the potential for greater prevention. A
      relatively low rate of maltreatment was recorded compared with that in some other
      studies.

PMID- 15568530
TI  - Surgical treatment of post-traumatic stiffness of the elbow.
AB  - Surgical release of the elbow was performed in 27 patients with post-traumatic
      stiffness at a mean of 14.5 months after the initial injury. The outcome was
      related to whether there had been heterotopic ossification, which had occurred in
      18 elbows and to whether, if there had been a fracture, it had involved the
      articular surface, which had occurred in 13 elbows. The final range of movement
      and the ratio of desired gain in each group were compared at a mean follow-up
      period of 22.5 months (12 to 43). The arc of movement of the elbow improved in
      all patients after the operation. The mean final arc was 110 degrees in those
      with heterotopic ossification and 86 degrees in those without (p = 0.001). The
      ratios of desired gain were significantly higher in patients with heterotopic
      ossification (88.2% vs 54.9%; p < 0.001). There was no significant difference in
      relation to involvement of the articular surface. Careful assessment of the cause
      of stiffness is important in order to achieve a satisfactory result from surgery
      for post-traumatic stiffness of the elbow.

PMID- 15568531
TI  - Sensory hypoinnervation in club foot.
AB  - We have compared the density of nerve fibres in the synovium in club foot with
      that of specimens obtained from the synovium of the hip at operations for
      developmental dysplasia. The study focused on the sensory neuropeptides substance
      P; calcitonin gene-related peptide; protein gene product 9.5, a general marker
      for mature peripheral nerve fibres; and growth associated protein 43, a neuronal
      marker for new or regenerating nerve fibres. In order to establish whether there
      might be any inherent difference we analysed the density of calcitonin gene
      related peptide-positive nerve fibres in the hip and ankle joints in young rats.
      Semi-quantitative analysis showed a significant reduction in the number of
      sensory and mature nerve fibres in the synovium in club foot compared with the
      control hips. Calcitonin gene-related peptide (CGRP) positive fibres were reduced
      by 28%, substance P-positive fibres by 36% and protein gene product 9.5-positive
      fibres by 52% in club foot. The growth associated protein 43-positive fibres also
      seemed to be less in six samples of club foot. No difference in the density of
      CGRP-positive nerve fibres was observed in the synovium between ankle and hip
      joints in rats. The lack of sensory input may be responsible for the fibrosis and
      soft-tissue contractures associated with idiopathic club foot.

PMID- 15568532
TI  - Supramalleolar derotation osteotomy of the tibia, with T plate fixation.
      Technique and results in patients with neuromuscular disease.
AB  - Torsional deformities of the tibia are common in children, but in the majority
      both the torsion and the associated disturbance of gait resolve without
      intervention. There are, however, a significant number of children and adults
      with neuromuscular disease who present with pathological tibial torsion, which
      may require surgical correction. We conducted a prospective study in two centres,
      to investigate the outcome of supramalleolar derotation osteotomy of the tibia,
      using internal fixation with the AO-ASIF T plate. A range of outcome variables
      was collected, prospectively, for 57 patients (91 osteotomies), including thigh
      foot angle, foot progression angle, post-operative complications and serial
      radiographs. Correction of thigh foot angle and foot progression angle was
      satisfactory in all patients. Three major complications were recorded; one
      aseptic nonunion, one fracture through the osteotomy site after removal of the
      plate and one distal tibial growth arrest. We found that supramalleolar
      derotation osteotomy of the tibia, with AO-ASIF T plate fixation is an effective
      method for the correction of torsional deformities of the tibia and the
      associated disturbances of gait in children and adults with neuromuscular
      disease, with a 5.3% risk of major complications.

PMID- 15568533
TI  - A paired study of Perthes' disease comparing conservative and surgical treatment.
AB  - We performed a paired study of mature patients with Perthes' disease to compare
      the radiological results after treatment between conservatively- and surgically
      treated groups. One patient was selected from each group to create the pairs for
      this study. Each pair was strictly matched for gender, body mass index, age at
      onset, stage at the first visit, necrotic area and radiological at-risk signs and
      each was assessed by comparing the values of six radiological measurements.
      Eighteen pairs (36 hips) fitted the criteria. The radiological measurements which
      showed a statistically better result in the surgical groups were Mose's method,
      the acetabular-head index and leg-length discrepancy. There were no statistical
      differences in the slope of the acetabular roof and the articulotrochanteric
      distance. Four hips in the conservative group were in Stulberg class II, five in
      class III and nine in class IV. In the surgical group, 13 were in Stulberg class
      II, four in class III and one in class IV. We conclude that surgical treatment
      improved the sphericity of the femoral head and provided greater acetabular
      cover, but did not reform the acetabular roof. It was noteworthy that a greater
      leg-length discrepancy and a smaller articulotrochanteric distance were not seen
      in the surgical group. Our study suggests that surgical treatment is preferable
      in patients with severe Perthes' disease.

PMID- 15568534
TI  - Recovery of function after closed femoral shortening.
AB  - This prospective, longitudinal study documents the muscle strength and baseline
      function of 18 patients undergoing closed femoral shortening for discrepancy in
      limb length. Patients were studied for two years following surgery. Function was
      measured by a self-reported questionnaire, timed tests of performance and
      measurements of muscle strength and power. After two years, the self-reported
      function and ability to complete timed functional tests had returned to or
      improved on the pre-operative values. Muscle strength remained slightly below the
      pre-operative value and was more marked in the quadriceps than the hamstrings.
      This study suggests that small decreases in muscle strength and power following
      closed femoral shortening do not adversely affect the patients' ability to
      perform everyday activities.

PMID- 15568535
TI  - Analysis of a retrieved delta III total shoulder prosthesis.
AB  - A reversed Delta III total shoulder prosthesis was retrieved post-mortem, eight
      months after implantation. A significant notch was evident at the inferior pole
      of the scapular neck which extended beyond the inferior fixation screw. This bone
      loss was associated with a corresponding, erosive defect of the polyethylene cup.
      Histological examination revealed a chronic foreign-body reaction in the joint
      capsule. There were, however, no histological signs of loosening of the glenoid
      base plate and the stability of the prosthetic articulation was only slightly
      reduced by the eroded rim of the cup.

PMID- 15568536
TI  - Fracture of a Y-TZP ceramic femoral head. Analysis of a fault.
AB  - We studied factors contributing to the initiation of fracture and failure of a
      zirconia ceramic femoral head. The materials retrieved during a revision total
      hip replacement were submitted to either visual, stereomicroscopic and scanning
      electron microscopy (SEM) or SEM and energy-dispersive X-ray analysis. X-ray
      diffraction was performed in order to investigate the extent of tetragonal to
      monoclinic phase transition. Histological examination was performed on the
      periprosthetic tissues. The results showed that failure was due to the
      propagation during clinical use of defects which may have been introduced into
      the material during the processing of the ceramic, rather than those intrinsic to
      zirconia. The literature relating to previous failures of zirconia components is
      reviewed.

PMID- 15568537
TI  - Intra-operative arthrography facilitates accurate screw fixation of a slipped
      capital femoral epiphysis.
AB  - We report the case of a 13-year-old obese child presenting with bilateral stable
      slipped capital femoral epiphyses, which were managed by percutaneous single
      screw fixation in situ under image intensifier control using arthrography.

PMID- 15568538
TI  - Tissue-engineered bone formation in vivo using a novel sintered polymeric
      microsphere matrix.
AB  - We have evaluated in vivo a novel, polymer-based, matrix for tissue engineering
      of bone. A segmental defect of 15 mm was created in the ulna of New Zealand white
      rabbits to determine the regenerative properties of a porous polylactide-co
      glycolide matrix alone and in combination with autogenous marrow and/or the
      osteoinductive protein, BMP-7. In this study four implant groups were used: 1)
      matrix alone; 2) matrix with autogenous marrow; 3) matrix with 20 microg of BMP
      7; and 4) matrix with 20 microg of BMP-7 and autogenous marrow. The results
      showed that the degree of bone formation was dependent on the properties of the
      graft material. The osteoconductive sintered matrix structure showed significant
      formation of bone at the implant-bone interface. The addition of autogenous
      marrow increased the penetration of new bone further into the central area of the
      matrix and also increased the degree of revascularisation. The osteoinductive
      growth factor BMP-7 induced penetration of new bone throughout the entire
      structure of the implant. The most effective treatment was with the combination
      of marrow cells and osteoinductive BMP-7.

PMID- 15568539
TI  - Apoptosis--a significant cause of bone cell death in osteonecrosis of the femoral
      head.
AB  - Osteonecrosis of the femoral head usually affects young individuals and is
      responsible for up to 12% of total hip arthroplasties. The underlying
      pathophysiology of the death of the bone cells remains uncertain. We have
      investigated nitric oxide mediated apoptosis as a potential mechanism and found
      that steroid- and alcohol-induced osteonecrosis is accompanied by widespread
      apoptosis of osteoblasts and osteocytes. Certain drugs or their metabolites may
      have a direct cytotoxic effect on cancellous bone of the femoral head leading to
      apoptosis rather than purely necrosis.

PMID- 15568540
TI  - Pre-heating of components in cemented total hip arthroplasty.
AB  - Fatigue fractures which originate at stress-concentrating voids located at the
      implant-cement interface are a potential cause of septic loosening of cemented
      femoral components. Heating of the component to 44 degrees C is known to reduce
      the porosity of the cement-prosthesis interface. The temperature of the cement
      bone interface was recorded intra-operatively as 32.3 degrees C. A simulated
      femoral model was devised to study the effect of heating of the component on the
      implant-cement interface. Heating of the implant and vacuum mixing have a
      synergistic effect on the porosity of the implant-cement interface, and heating
      also reverses the gradients of microhardness in the mantle. Heating of the
      implant also reduces porosity at the interface depending on the temperature. A
      minimum difference in temperature between the implant and the bone of 3 degrees C
      was required to produce this effect. The optimal difference was 7 degrees C,
      representing a balance between maximal reduction of porosity and an increased
      risk of thermal injury. Using contemporary cementing techniques, heating the
      implant to 40 degrees C is recommended to produce an optimum effect.

PMID- 15568541
TI  - The influence of immediate surgical treatment of proximal femoral fractures on
      mortality and quality of life.

PMID- 15568542
TI  - Arthroplasty of the elbow in haemophilia.

PMID- 15568544
TI  - Public images of occupational therapy.

PMID- 15568543
TI  - Arthroscopic debridement in the treatment of the infected total knee replacement.

PMID- 15568545
TI  - The 2004 Eleanor Clarke Slagle Lecture--Time, space, and the kaleidoscopes of
      occupation.
AB  - Our daily round of occupations occurs within time and space. Our understanding of
      occupation has traditionally viewed time and space as part of the external
      environment. Patterns of the "when?" and "where?" of occupations can be
      described. But relating time and space to the internal experience of occupation
      reflects more of the meaning to individuals and more complex patterns arise. Like
      the varied bits of glass in the object case of an art kaleidoscope, the multiple
      elements of occupation interact. Reflected in mirrors of our choice, we find
      always-changing, complex patterns of daily occupation. The elements of occupation
      most important for maintaining or regaining health and the mirrors and lens
      through which we view occupation historically have formed shifting patterns in
      occupational therapy, patterns of how we view ourselves, our practice, and those
      to whom we provide our services. We must combine the science and the art of
      occupational therapy as the metaphor of the kaleidoscope combines both, producing
      awe and wonder at the result.

PMID- 15568546
TI  - Functional performance in children with Down syndrome.
AB  - OBJECTIVES: The purpose of this study was to describe home and community
      functional performance in 5-year-old children with Down syndrome. METHOD: In a
      cross-sectional study of 5-year-old children with Down syndrome in Norway (N=43),
      functional performance was measured with the Norwegian translation of the
      Pediatric Evaluation of Disability Inventory (PEDI). Additional descriptive
      information related to health, disabilities, and function was also gathered.
      RESULTS: The children showed a wide range of functional performance. Performance
      of self-care activities appeared most delayed on activities that required fine
      motor skills. Children appeared less affected in basic functional mobility
      skills. Parents' identified their main concerns as language functioning and, for
      the children not yet toilet trained, the management of bladder and bowel control
      in relation to starting school. CONCLUSION: The results provide baseline
      information regarding typical levels of functional performance in children with
      Down syndrome at 5 years of age. However, the broad range of functional
      performance across children indicates a need for caution in generalizing the
      results to an individual child.

PMID- 15568547
TI  - Allocation of rehabilitation services: who gets a home evaluation.
AB  - OBJECTIVE: The purpose of this study was to (a) identify and describe the
      subpopulation of rehabilitation inpatients who receive specialized occupational
      therapy home evaluation services, and (b) examine these data for evidence of
      inequalities in access to services based on patient gender, race, age, and health
      insurance status. METHOD: An archival review was conducted of all inpatient
      admissions (7,871) to a large urban rehabilitation hospital between January 1,
      1994, and December 31, 1998. We had complete data on 7,791 of these patients of
      whom 6,038 were eligible to receive a home evaluation. Patient demographic data
      and Functional Independence Measure (FIM) data were obtained in electronic form
      from the hospital information system. RESULTS: Analysis showed that 12.4%
      (749/6038) of eligible inpatients received an in-home evaluation, and those who
      did were significantly more dependent (as measured by the FIM) than those who did
      not (p < 0.0001). We found no evidence of inequalities in access to this
      specialized rehabilitation service on the basis of gender, race, age, and type of
      medical insurance after controlling for level of functional independence.
      CONCLUSIONS: This study found no evidence of inequalities in the allocation of
      home evaluation services. However, it raises the larger question of how we
      determine whether inequalities exist. A proper assessment of inequalities in
      service provision requires that we know the principles by which these services
      should be allocated and have appropriate measures of the application of these
      principles. For programmatic and policy reasons, more research is needed to
      develop well-defined principles of resource allocation, and adequate measures of
      their impact so we can know whether resources and services are distributed in the
      way we intend.

PMID- 15568548
TI  - Improving dyspnea management in three adults with chronic obstructive pulmonary
      disease.
AB  - This case report describes occupational therapy intervention for three adult
      outpatients with chronic obstructive pulmonary disease (COPD) at one large urban
      hospital. The occupational therapy intervention was based on the Management of
      Dyspnea Guidelines for Practice (Migliore, in press). The learning and practice
      of controlled breathing were promoted in the context of physical activity
      exertion in a domiciliary environment. In addition to promoting dyspnea
      management, the controlled-breathing strategies aimed to facilitate energy
      conservation and to increase perceived breathing control. Although no causality
      can be determined in a case study design, the patients' dyspnea with activity
      exertion decreased and their functional status and quality of life increased
      following goal-directed, individualized occupational therapy intervention
      combined with exercise training.

PMID- 15568549
TI  - Role competencies for a professional-level occupational therapist faculty member
      in an academic setting (Roles** Document) (2003).

PMID- 15568550
TI  - Role competencies for a professional-level program director in an academic
      setting (Roles** Document) (2003).

PMID- 15568551
TI  - Role competencies for an academic fieldwork coordinator (Roles** Document)
      (2003).

PMID- 15568552
TI  - Enforcement procedures for occupational therapy code of ethics (2004).

PMID- 15568553
TI  - Guidelines for supervision, roles, and responsibilities during the delivery of
      occupational therapy services (2004).
AB  - These guidelines about supervision, roles, and responsibilities are to assist in
      the appropriate utilization of occupational therapy personnel and in the
      appropriate and effective provision of occupational therapy services. All
      personnel are expected to meet applicable state and federal regulations, adhere
      to relevant workplace policies and the Occupational Therapy Code of Ethics (AOTA,
      2000), and participate in ongoing professional development activities to maintain
      continuing competency.

PMID- 15568554
TI  - Occupational therapy's commitment to nondiscrimination and inclusion (edited
      2004).

PMID- 15568555
TI  - Psychosocial aspects of occupational therapy (2004).

PMID- 15568556
TI  - Scope of practice (2004).

PMID- 15568557
TI  - Assistive technology within occupational therapy practice (2004).

PMID- 15568558
TI  - Occupational therapy services in early intervention and school-based programs
      (2004).

PMID- 15568559
TI  - [Ekaterinburg Russian Health Ministry Medical Research Center for prophylaxis and
      health preservation of industrial workers--history present and prospects (to 75th
      anniversary of foundation)].

PMID- 15568560
TI  - ["Industrial Hygiene" system as a basis of medical service for workers in
      Sverdlovsk region].
AB  - The authors suggest a concept of multifield specialized "Industrial Hygiene"
      service based on integrated system of medical and social care, that includes
      monitoring of work conditions, evaluation of occupational risk and its management
      for prevention of and lowering general and occupational morbidity, transitory
      disablement morbidity, disability and premature deaths, for preservation of
      labour force in Sverdlovsk region.

PMID- 15568561
TI  - [Rehabilitation for dwellers of ecologically unfavorable territories of
      Sverdlovsk region].
AB  - The article covers organizational and methodic aspects associated with creation
      of rehabilitation system for dwellers of ecologically unfavorable territories of
      Sverdlovsk region.

PMID- 15568562
TI  - [Providing safe environment for health of population living near aluminium
      industry enterprises].
AB  - Based on studies of environmental objects and of children's health, the authors
      justified systematic approach to hygienic evaluation of aluminium plant
      reconstruction stages, for rational management in minimizing risk of
      environmental pollution and for health preservation.

PMID- 15568563
TI  - [Contemporary problems of asbestos and prospective research directions].
AB  - The authors determined prospective directions in researchon asbestos problem-
      risk evaluation, early diagnosis and physiotherapy of asbestos-related diseases;
      sanitary and epidemiologic well-being of population influenced by enterprises
      extracting and concentration of asbestos; evaluation of new production and
      development of legal regulation of safety for work with natural and artificial
      mineral fibers.

PMID- 15568564
TI  - [Biologic prophylaxis of intoxications with inorganic compounds].
AB  - The authors summarize theoretical principles of increasing human resistence to
      toxic effects of inorganic compounds polluting occupational environment and
      habitat, exemplify practical use of this prophylactic trend.

PMID- 15568565
TI  - [Priority topics of industrial medicine in production and processing of
      nonferrous metals alloys].
AB  - The authors present general characteristics of nonferrous metals alloys
      production: work conditions, health state of workers, main directions to make
      healthier work conditions.

PMID- 15568566
TI  - [Basic hygiene of organizing the systems of household and drinkable water
      supplies in Middle Urals].
AB  - The authors suggest a methodology of decision making in organization of
      centralized household and drinkable water supplies, with consideration of local
      peculiarities.

PMID- 15568567
TI  - [Features of chronic occupational bronchitis in nonferrous metallurgy workers].
AB  - The authors summarized results of periodic medical examinations and deep clinical
      studies of metallurgy workers with bronchial and pulmonary disorders. The article
      covers clinical and functional characteristics of toxic and dust bronchitis,
      clinical course and manifestations.

PMID- 15568568
TI  - [Primary and secondary prophylaxis of vibration disease caused by local vibration
      in miners].
AB  - The article contains data on complex balneotherapy of vibration disease caused by
      local vibration in high risk group (miners exposed to vibration), that help to
      justify use of means for primary and secondary prevention of vibration disease.

PMID- 15568569
TI  - ["Shoulder pain syndrome" as an occupationally conditioned disease].
AB  - Analysis of medical examination materials through loglinear method and logistic
      regression revealed high risk of shoulder pain syndrome in individuals subjected
      to physical overload of shoulder and to fluorides toxicity. Prevalence of
      shoulder pain syndrome is also influenced by concomitant visceral diseases. The
      results obtained support possible use of the method in occupational risk
      calculation.

PMID- 15568570
TI  - [Prevention therapy of occupationally conditioned maladaptions in workers].
AB  - Medical examinations of workers with long length of service and subsequent
      biorhythmologic research revealed increased disorders in structure of temporal
      coordination of physiologic functions. Efficiency of suggested variants of
      correction therapy is supported by long working experience of sanatoriums and
      preventoriums.

PMID- 15568571
TI  - [Basing the problem of contemporary hygienic regulation of ambient air
      pollution].

PMID- 15568572
TI  - [Monitoring natural healing resources of Urals].

PMID- 15568573
TI  - Biometric and single-sign-on technologies cure the passwords 'haddock'.

PMID- 15568574
TI  - Two technologies let hospitals pass on words.

PMID- 15568575
TI  - Bar codes ready to go code red.

PMID- 15568576
TI  - Nurses line up at the I.T. suggestion box.

PMID- 15568577
TI  - Memoirs of Wi-Fi networks.

PMID- 15568578
TI  - Mobile technology comes from behind.

PMID- 15568579
TI  - Hospital dashes to wireless services.

PMID- 15568580
TI  - Rare diseases: medical attitudes are changing.

PMID- 15568581
TI  - The role of stenting in the tracheobronchial tree.

PMID- 15568582
TI  - Evaluation of a 5-year school-based county-wide smoking education programme.
AB  - Reports on an evaluation of Smoke Free Leitrim (SFL): a five-year (1996-2001)
      school-based county-wide smoking education programme that was offered to all
      fourth class students in all county Leitrim primary schools (n = 450). By
      programme end 208 (59%) SFL students and 147 (55%) of the control group had tried
      smoking. Sixty-six (19%) of the SFL group and 63 (24%) of the control group
      currently smoke. No significant differences were found between the groups for
      current smoking. Daily smoking of SFL and control males was identical: SFL 19
      (10%); control 12 (10%). There was a significant difference between daily smoking
      of females: 14 (8%) SFL girls and 24 (16%) control group girls smoke everyday.
      The SFL intervention did not delay or prevent the uptake of smoking, but may have
      had some gendered effect. It reflected the limited effectiveness of long-term
      wide-scale smoking education interventions. A more sophisticated approach to
      young people and tobacco usage is required, that extends beyond the school to
      focus on tobacco usage in adults, families and the wider community.

PMID- 15568583
TI  - Breast is best for GPs--or is it? Breastfeeding attitudes and practice of general
      practitioners in the Mid-West of Ireland.
AB  - In light of the 1994 National Breastfeeding Policy and the 1999 Mid-Western
      Health Board (MWHB) Breastfeeding Strategy, a telephone survey of 164 General
      Practitioners (GPs) in the Mid-West was performed to ascertain their attitudes
      and practice in relation to breastfeeding. 95% believe breastfeeding promotion is
      part of their role and almost 40% consider GPs influential in the decision to
      breastfeed. Less than 10% have formal breastfeeding training, while 1/3 would be
      interested in formal training. 80% promote breastfeeding, and 90% are confident
      to deal with breastfeeding problems. Those with formal training reported higher
      promotion and confidence rates, and scored higher on management scenarios, GPs in
      the Mid-West of Ireland have positive attitudes towards breastfeeding. Training
      in relation to breastfeeding appears lacking, however. Formal training appears to
      confer advantage, and if, made accessible to interested GPs has the potential to
      positively influence breastfeeding rates.

PMID- 15568584
TI  - Prescribing trends for nicotine replacement therapy in primary care.
AB  - Nicotine replacement therapy (NRT) has been available free of charge for medical
      cardholders in Ireland (29.84% of the population) since April 2001. We
      investigate the prescribing patterns for NRT before and after this change in
      reimbursement status. Using the General Medical Services Payments Board
      prescription database we conducted a detailed analysis of NRT prescribing (ATC
      code N07BA) for those patients eligible for free medications (1,168,745 patients)
      in all health board areas in Ireland from January to December 2002. We determined
      the number of monthly prescriptions for each NRT preparation (ATC code N07BA01)
      and bupropion (ACT code N07BA02) together with total expenditure. The mean
      dosage, duration of therapy and age/gender distribution of NRT treatment was also
      obtained. We identified 49,826 patients who received smoking cessation products
      in 2002. Of these 94.6% (47,147 patients) were prescribed NRT, the remaining 5.4%
      (2,679 patients) received bupropion. Nicotine patch therapy accounted for 82.8%
      of all NRT dispensed. Prescribing trends for NRT show the number of patients
      receiving such therapy is greatest in January and February with expenditure
      highest in the first quarter. Prescribing of NRT is greatest amongst the 25-54
      year age group with peak prescribing between the ages of 35-44 years. The highest
      dose of nicotine patch therapy (15-21 mg/day) was prescribed for the majority
      (73%) of patients. Over three quarters (75.6%) of all patients were prescribed
      nicotine patch therapy for a period of less than or equal to 4 weeks (48.1% less
      than or equal to 2 weeks). Similarly for nicotine gum where 77% of all patients
      received just one month of therapy. This analysis indicates quality NRT
      prescribing in the primary care setting. The dose and duration of therapy is in
      keeping with recent NICE guidance indicating that the NRT expenditure of
      2,709,954 euros in 2002 should provide value for money.

PMID- 15568585
TI  - Folic acid supplements to prevent neural tube defects: trends in East of Ireland
      1996-2002.
AB  - Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for
      ten years in Ireland, without a concomitant reduction in the total birth
      prevalence of NTD. The effectiveness of folic acid promotion as the sole means of
      primary prevention of NTD is therefore questionable. We examined trends in folic
      acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing
      the value of this approach. From 1996-2002, 300 women attending ante-natal
      clinics in Dublin hospitals annually were surveyed regarding their knowledge and
      use of folic acid. During the period the proportion who had heard of folic acid
      rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001).
      Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for
      trend: p<0.001). Although the proportion who took folic acid during pregnancy
      increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri
      conceptional intake did not rise above 24% in any year. There is a high awareness
      of folic acid and its relation to NTD, which is not matched by peri-conceptional
      uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy
      planning. To date promotional campaigns appear to have been ineffective in
      reducing the prevalence of NTD in Ireland. Consequently, fortification of staple
      foodstuffs is the only practical and reliable means of primary prevention of NTD.

PMID- 15568586
TI  - Spotlight on teenage pregnancy--defining the demographics and the family planning
      requirements.
AB  - This study aims to provide a demographic analysis of teenage pregnancy and a
      needs-assessment for teenage family planning. A questionnaire was sent to all
      teenage mothers delivered in 2000 in Waterford Regional Hospital (WRH), and
      demographic analysis was performed. There were 118 teenage pregnancies, only 88%
      were primigravid, and 24% were aged <17 years. The response rate was 43%. The
      uptake of contraception before pregnancy was 74%, (42% using barrier methods
      only), and post-partum, the uptake was 98%, (12% barrier methods). The majority
      of teenagers (72%) prefer to attend the General Practitioner, preferably with an
      out-of-hours, weekday service. Teenage family planning is an area of need,
      particularly in the younger teen-years and following a pregnancy. We have shown
      how this can be addressed.

PMID- 15568587
TI  - The burden of severe pneumococcal infection in Ireland: potential effectiveness
      and indirect benefits of the 7-valent pneumococcal conjugate vaccine.
AB  - This study attempts to overcome the problem of under-reporting of serious
      pneumococcal infection in the Republic of Ireland by adding a proportion of
      'unspecified' disease to pneumococcal disease reports. ICD-9 data for all age
      groups was collected on meningitis (from the National Disease Surveillance
      Centre), and septicaemia and pneumonia (from the Hospital In-Patient Enquiry
      system) for the year 1999. A 7-valent pneumococcal conjugate vaccine (PCV) has
      been shown to have significant effectiveness in the target paediatric age group
      and also indirect herd effects on the US adult population. The implications of
      these direct and indirect effects were applied to the epidemiology of serious
      pneumococcal infection in Ireland. The annual reported incidence rates for
      laboratory confirmed severe pneumococcal disease in Ireland in 1999 may
      underestimate both the morbidity and mortality of disease by 21% and 28%
      respectively. In all age groups 1,183 cases and 132 deaths may be prevented
      annually by the introduction of the vaccine. In addition, the vaccine provides an
      effective new tool for reducing disease caused by antibiotic resistant
      pneumococci thus assisting in the control of anti-microbial resistance in humans.

PMID- 15568588
TI  - Auditing a new lung cancer service.
AB  - The Adelaide and Meath Hospital (AMNCH) is a new hospital, with the respiratory
      service established in 1999. We report on our experience with lung cancer in this
      short time. We conducted a retrospective chart audit, identifying patients from
      the Oncology Nurse patient list, of lung cancer cases diagnosed in 2001-2002. In
      2001, 47 cases were diagnosed, with 71 cases diagnosed in 2002. Time to tissue
      diagnosis was 14.8, 2-46 (mean, range, one subject skewing the data) days.
      Diagnosis by tissue type was as follows: non-small cell carcinoma (NSCLC) n=92
      (77.9%), small cell lung carcinoma (SCLC) n=17 (14.4%), mesothelioma n=2 (17%),
      carcinoid n=1 (0.8%) and no tissue diagnosis n=6 (5.1%). Staging of NSCLC: stage
      1a n=3 (3.2%), stage 1b n=6 (6.5%), stage 2a n=5 (5.4%), stage 2b n=2 (2.2%),
      stage 3a n=10 (10.9%), stage 3b n=22 (23.9%) and stage 4 n=44 (47.8%). Staging of
      SCLC: limited stage n=5 (29.4%), extensive stage n=12 (70.6%). Positive emission
      tomography (PET) was employed in the staging of 22 patients. In these patients
      PET up-staged the disease in 8 patients, and management was unchanged in 8
      patients. We conclude that 1. the relatively new respiratory service in AMNCH is
      handling increasing numbers of lung cancer cases, 2. cases are diagnosed within
      an acceptable time-frame, 3. rate of tissue diagnosis is comparable to national
      figures, 4. most patients present with advanced disease and 5. PET is a useful
      imaging modality for detection of cancer spread in selected patients.

PMID- 15568589
TI  - Neurocysticercosis: a rare cause of seizure.
AB  - Neurocysticercosis is endemic in certain parts of the world, is rare in Europe
      and has never previously been described in the Irish healthcare setting. We
      report the case of a healthy male, originally from Guatemala, who presented to
      our hospital with a generalized tonic-clonic seizure presumed secondary to
      neurocysticercosis.

PMID- 15568590
TI  - Primary prevention of sudden cardiac death. do we need to implant a defibrillator
      in all the patients with low ejection fraction?

PMID- 15568591
TI  - Aortic dissection: diagnosis, state-of-the-art of imaging and new management
      acquisitions.
AB  - A prompt diagnosis is the cornerstone of effective treatment of aortic dissection
      and it is the single most important determinant of survival in this patient
      population. New imaging modalities such as transesophageal echocardiography,
      magnetic resonance imaging, helical computed tomography and electron-beam
      computed tomography have been introduced during the last decade. These new
      imaging techniques allow for a better and earlier diagnosis of aortic diseases
      even in emergency situations. Bearing in mind the high overall mortality of
      aortic dissection, the role of prevention cannot be overstressed. The main risk
      factor for aortic dissection/rupture is the aortic diameter; therefore we would
      like to stress the role of aortic replacement as an effective preventive method
      for aortic dissection/rupture. Determining the right time for elective surgery,
      when the operative risk is lower than the risk of dilation-related complications,
      could contribute to a decrease in urgent surgical procedures on the ascending
      aorta.

PMID- 15568592
TI  - Infective endocarditis: transesophageal echocardiography in all or in selected
      cases? When is echocardiography highly predictive for complications?
AB  - Echocardiography is currently considered one of the most important tools in the
      diagnosis and treatment of infective endocarditis (IE). However, its use leaves a
      number of issues open. Since transthoracic echocardiography (TTE) cannot define
      structures and vegetations < 4 mm, transesophageal echocardiography (TEE), though
      more costly and invasive, is superior to TTE in the diagnosis of IE. TEE should
      be recommended immediately in patients with valve prostheses and in those with a
      native valve and an intermediate or high pre-test probability of disease. In
      patients with a low probability of disease, a completely negative examination
      without the slightest valvular anomaly practically excludes the likelihood of IE;
      however, the patient should still be followed up. In patients with a very low
      probability of disease, echocardiography is not necessary; instead, reassessment
      can be performed at some future time. Echocardiography has a high prognostic
      value in IE since it may reveal intracardiac complications due to this disease
      and contributes to a better understanding of the clinical complications.
      Moreover, echocardiography may also aid in the choice of surgery timing and thus
      modify the clinical progression of the disease. Large and extensive vegetations
      that are more mobile and soft are more closely associated with the development of
      complications and embolic events. Despite numerous reports, uncertainty surrounds
      the approach to treatment when echocardiography discloses vegetations at risk of
      embolization in uncomplicated IE and in the absence of other indications for
      surgery.

PMID- 15568593
TI  - Treatment synergy of silicon carbide-coated stenting and abciximab for complex
      coronary artery lesions: clinical results of a single-center study.
AB  - BACKGROUND: The aim of this study was to evaluate the combination of a silicon
      carbide-coated stent with the periprocedural use of abciximab in patients with
      type B2/C lesions. The study was a prospective cohort study and was conducted at
      the University Medical Center of Groningen. METHODS: Elective percutaneous
      transluminal coronary angioplasty was performed in a total of 44 patients. All
      had lesions with type B2/C characteristics and most were relatively small,
      tortuous and calcified. The involved vessel segment was stented. Silicon carbide
      coated stents were used in combination with periprocedural abciximab. The main
      outcome measures were cardiac death, target vessel revascularization, myocardial
      infarction, and cerebrovascular accident. RESULTS: At 6 months of follow-up, only
      4 patients had a major adverse cardiac event. Three patients had undergone target
      vessel revascularization and 1 patient had suffered from a cerebrovascular
      accident. Sixteen patients underwent re-angiography 6 months after the initial
      procedure. The average stenosis at 6 months was 15% with a minimal lumen diameter
      of 2.4 mm. CONCLUSIONS: A 9% major adverse cardiac event rate and a 7% target
      vessel revascularization rate at 6 months in type B2/C lesions were recorded.
      Further investigation on the use of this specific treatment combination is
      warranted.

PMID- 15568594
TI  - Effect of a short antibiotic treatment with roxithromycin on circulating adhesion
      molecules after coronary stenting: a single-center pilot trial.
AB  - BACKGROUND: The aim of this study was to assess the effect of periprocedural
      antibiotic treatment with roxithromycin on circulating cell adhesion molecules
      and restenosis after coronary stent implantation. METHODS: Case-control study
      enrolling 25 consecutive patients submitted to coronary stenting for stable,
      single-vessel coronary artery disease, treated with 300 mg roxithromycin once
      daily for 5 days, starting 2 days before the procedure (group R). Twenty-five
      patients, matched for lesion site, length and diameter, as control group (group
      C). The serological status for Chlamydia pneumoniae (CP) infection (IgG, ELISA)
      was assessed in all patients. The plasma concentrations of soluble intercellular
      adhesion molecule-1 (sICAM-1), E-selectin and C-reactive protein at 1 month after
      coronary stenting were compared with baseline values. Binary restenosis (> or =
      50%) was also evaluated at 6 months. RESULTS: sICAM-1 significantly decreased at
      1 month in group R vs group C (371 +/- 181 vs 573 +/- 273 ng/ml, p = 0.005). This
      decrease was more evident in patients with a positive serology for CP (CP+)
      (group R 373 +/- 131 vs group C 597 +/- 255 ng/ml, p = 0.014). Antibiotic
      treatment had no effects on circulating E-selectin levels at 1 month (56.7 +/- 97
      vs 49.8 +/- 62 ng/ml, p = 0.54). The restenosis rate (9/50, 18%) was similar in
      the two groups (group R 5/25 [20%], group C 4/25 [16%]). The restenosis rate was
      similar in the CP+ vs CP- group (6/35 [17%] vs 3/15 [20%]). CONCLUSIONS: A short
      course of treatment with roxithromycin at the time of coronary stenting induces a
      significant reduction in the sICAM-1 levels at 1 month but apparently does not
      influence the restenosis rate.

PMID- 15568595
TI  - Suitability of stentless bioprostheses for combined replacement of the aortic
      valve and ascending aorta.
AB  - BACKGROUND: The Edwards Prima stentless valve (EPSV) is a bioprosthesis made of
      the porcine aortic root which, owing to its versatility, may be implanted with
      different techniques depending on the underlying disease. The aim of this study
      was to demonstrate the usefulness of the EPSV implanted as a miniroot in patients
      with disease of the aortic valve and ascending aorta. METHODS: Between January
      1998 and July 2002, 91 patients (mean age 67 +/- 7 years) underwent combined
      replacement of the aortic valve and ascending aorta with an EPSV for aortic
      stenosis (n = 12), incompetence (n = 45) or mixed disease (n = 26); all had
      aneurysmal dilation of the ascending aorta and 8 had an acute aortic dissection.
      The EPSV was implanted using the miniroot (or inclusion) technique and by
      extending the aorta with a tubular graft; aortic arch replacement was required in
      5 patients. Hospital survivors underwent clinical and echocardiographic follow-up
      at 6 and 12 months and yearly thereafter. RESULTS: The hospital mortality was 11%
      (10 patients). Causes of death included stroke (n = 3), septic shock (n = 3),
      myocardial infarction (n = 2), and low output syndrome (n = 2). The mean follow
      up of the 81 discharged patients was 16 +/- 13 months and was 100% complete;
      there were 6 late deaths due to non-cardiac causes. All patients presented with
      clinical improvement (95% are in NYHA functional class I) with low transvalvular
      gradients and significant regression of left ventricular hypertrophy at two
      dimensional echocardiography. CONCLUSIONS: The EPSV used as a miniroot has proved
      to be a valid option in patients requiring simultaneous replacement of the aortic
      valve and ascending aorta. Due to the limited information available on the long
      term fate of the porcine aortic valve and root, the use of this device as a
      miniroot should presently be limited to elderly patients.

PMID- 15568596
TI  - Half-dose thrombolysis to begin with, when immediate coronary angioplasty in
      acute myocardial infarction is not possible.
AB  - BACKGROUND: Low-dose lytic drugs are sometimes administered to patients with ST
      elevation acute myocardial infarction (AMI) as a bridge to coronary angioplasty
      (facilitated PTCA). Reports are scarce. The characteristics and outcomes of a
      recent series of consecutive patients treated in our Center are presented.
      METHODS: In August 2000 facilitated PTCA with half-dose reteplase was started in
      our Center in all cases when the cath lab was not immediately (< 30 min)
      available, or the patient had to be transferred to us. Since August 2000, 153
      patients were admitted to our cath lab to undergo facilitated (n = 80) or primary
      (n = 73) PTCA. The data of all patients were prospectively collected, and were
      analyzed on an "intention-to-treat" basis. RESULTS: No significant differences
      were found between facilitated and primary PTCA patients with regard to: gender,
      diabetes, hypertension, previous PTCA/bypass surgery, heart rate at admission,
      systolic blood pressure, anterior AMI, number of leads with ST-segment elevation,
      total ST-segment deviation, collateral flow to the infarct-related artery, and
      three-vessel disease. In our series, facilitated vs primary PTCA patients had a
      better risk profile: they were younger (61 +/- 13 vs 66 +/- 11 years, p = 0.016),
      less frequently had a previous AMI (7 vs 24%, p = 0.01), had a shorter time from
      pain onset to first emergency room admission (122 +/- 104 vs 168 +/- 162 min, p =
      0.045), and a trend to a shorter total time to the cath lab (209 +/- 121 vs 255
      +/- 183 min, p = 0.073) despite a similar emergency room-to-cath lab component
      (89 +/- 50 vs 98 +/- 92 min, median 74 vs 65 min, p = NS). Moreover, they
      presented with a lower Killip class on admission (1.1 +/- 0.4 vs 1.5 +/- 0.98, p
      = 0.01), with more patients in Killip class 1 (95 vs 74%, p = 0.001). One vs 8%
      of patients were in shock. Facilitated vs primary PTCA patients had an initial
      TIMI 2-3 flow in 42 vs 25% of cases (p = 0.031), a final TIMI 3 flow in 82 vs 71%
      (p = NS), > or = 50% ST-segment resolution in 73 vs 58% (p = NS), and both of the
      latter in 62 vs 45% (p = 0.099); distal coronary embolization occurred in 9 vs
      14% of cases (p = NS); intra-aortic balloon counterpulsation was used in 5 vs 12%
      and glycoprotein IIb/IIIa inhibitors in 10% of the whole population. The overall
      in-hospital mortality was 3.7 vs 9.6% (p = NS), and 2.5 vs 4.5% (p = NS) when
      patients in shock at admission were not considered. Reinfarction occurred in 2
      patients submitted to facilitated PTCA (who had had no immediate PTCA, due to
      full reperfusion) and in none of the patients submitted to primary PTCA; no
      patient presented with stroke or major bleeding. CONCLUSIONS: Pre-treatment with
      thrombolysis often provides a patent vessel before PTCA, appears to be safe, and
      may improve reperfusion after PTCA. In this setting, the additional use of
      glycoprotein IIb/IIIa inhibitors before PTCA only in non-reperfused patients may
      be significantly risk- and cost-effective.

PMID- 15568597
TI  - ST-elevation acute myocardial infarction: can we improve the results of primary
      percutaneous coronary intervention?

PMID- 15568598
TI  - Invasive strategy following fibrinolysis in ST-elevation acute myocardial
      infarction.
AB  - BACKGROUND: A recognized drawback of ST-elevation acute myocardial infarction
      (STEMI) after fibrinolysis is persistent coronary occlusion or a less than TIMI 3
      flow. The present study describes the results of systematic pre-discharge
      coronary angiography and revascularization, whenever indicated, following
      fibrinolytic therapy for STEMI. METHODS: Consecutive patients admitted with the
      diagnosis of STEMI between April 1, 2000 and April 30, 2002 were included in the
      study. Patients with contraindications to thrombolytic therapy and/or patients
      not eligible for angiography were excluded. All patients received "accelerated"
      treatment with alteplase and had a coronary angiography at least 24 hours later,
      in order to perform, if anatomically feasible, angioplasty with stenting.
      Angioplasty of non-infarct-related coronary arteries was allowed. The mortality,
      reinfarction and new revascularization rates were evaluated during index
      hospitalization and up to 30 days and 6 months. RESULTS: Eighty patients
      underwent cardiac catheterization at a median of 6.5 days following admission; in
      86.3% of cases a patent infarct-related artery was found; in 71% of patients a
      coronary angioplasty was performed, with stenting in 88% of cases. Procedure
      related complications were infrequent. No deaths occurred during hospitalization
      and at 30 days; at 6 months the mortality rate was 1.3%. In-hospital reinfarction
      occurred in 3.8% of patients, in 4% at 30 days and in 5.3% at 6 months. The rate
      of any new revascularization was 2.6% at 30 days and 11% at 6 months.
      CONCLUSIONS: Although obtained in a small observational study, our data, unlike
      those from previous studies, suggest that an invasive strategy after fibrinolysis
      in STEMI is safe and associated with low mortality and morbidity rates in the
      short and medium-terms.

PMID- 15568599
TI  - Dobutamine effects on spontaneous variability of ventricular arrhythmias in
      patients with severe chronic heart failure: the Italian Multicenter Study.
AB  - BACKGROUND: Dobutamina Studio Italiano Multicentrico (Do.S.I.M.) is a
      prospective, randomized, multicenter interuniversity Italian study aimed at
      assessing the effects of dobutamine on spontaneous variability of ventricular
      arrhythmias in sinus rhythm NYHA class III-IV patients with congestive heart
      failure (CHF). METHODS: Out of 74 pre-hoc estimated CHF patients, 68 (92%) were
      randomized electively to either being washed out of all active drugs except
      diuretics (group A) or to continue with the standard regimen including digitalis,
      diuretics and ACE-inhibitors (group B, standard therapy). In 63 patients,
      complete Holter data were obtained and are reported here. After 72 hours, in both
      groups, 48-hour Holter monitoring (Holter 1) was performed. The spontaneous
      variability of ventricular arrhythmias was assessed by calculating the natural
      logarithm of the sum of hourly incidences (during 48 consecutive hours) of index
      events such as the mean heart rate or the various forms of total and either
      sustained or non-sustained ventricular arrhythmias. The results were then grouped
      for the first and second 24-hour Holter periods. All patients were submitted to
      10 microg/kg/min infusion of dobutamine for 72 hours and 48-hour Holter
      monitoring (Holter 2) was repeated 24 hours before the end of dobutamine
      infusion. The incidence of arrhythmia and the distribution of laboratory and
      echocardiographic variables was also studied in group A and B patients. The data
      of the two groups along with the intrapatient +/- 95% confidence intervals were
      pooled, both on and off dobutamine. RESULTS: There was no significant difference
      between Holter 1 and Holter 2 in the rates of index events in 63 patients with
      regard to pro-arrhythmic effects. Pro-arrhythmic effects were seen during
      dobutamine infusion in 21% of cases, an effect which subsided (to 5%) when
      dobutamine was discontinued. Interestingly, the positive inotropic effects of
      dobutamine (based on ejection fraction changes) were parallel (22%) to the pro
      arrhythmic changes, although they persisted long after dobutamine discontinuation
      (18%). The pro-arrhythmic effects of dobutamine, both during (5%) as well as
      after (1%) drug infusion, were unrelated to heart rate changes. The prevalence
      and incidence of non-sustained ventricular tachycardia due to dobutamine were 47
      and 29% respectively. CONCLUSIONS: In sinus rhythm patients with severe CHF,
      dobutamine had chronotropic effects and increased a depressed ejection fraction
      without significantly increasing arrhythmogenicity.

PMID- 15568600
TI  - Fatal myocarditis: morphologic and clinical features.
AB  - BACKGROUND: Autopsy studies report a frequency of myocarditis ranging from 0.11
      to 5.5% in the general population, reaching almost 50% in selected groups.
      Myocarditis is often undiagnosed and the incidence of fatal course myocarditis
      has never been evaluated. The aim of our study was to assess the frequency of
      fatal course myocarditis in a consecutive series of autopsies and to describe the
      clinical, histological and morphologic features of the disease. METHODS: From
      January 1, 1995 to January 31, 1996, 2560 autopsies were performed, and 143 cases
      of active myocarditis were diagnosed (5.6%). RESULTS: In 39 cases (1.5%; 12
      males; 4/39 aged < or = 35 years) active myocarditis was identified as the final
      cause of death. Only in 1 case was myocarditis suspected ante-mortem. The
      histological pattern was lymphocytic in 64% of cases. A mixed inflammatory
      infiltration was found in 33% and a granulomatous infiltration in 3%. In 49% of
      cases myocarditis was localized in both ventricles and the interventricular
      septum. The clinical presentation of myocarditis was heart failure in 18/39
      patients (46%), cardiac arrest in 4/39 patients (10%) and syncope and chest pain
      in 1/39 patient (3%). The mean creatine phosphokinase levels were 890 +/- 2742
      IU/I (assessed in 11/39 patients, 28%) but they were increased only in 7/39
      (18%). ECG (performed in 29/39 patients, 74%) showed sinus rhythm in 16/39
      patients (55%, > 100 b/min in 41%), atrioventricular or interventricular
      conduction defects in 10/39 patients (34%) and a pathological Q wave in 4/39
      patients (14%). At echocardiography (performed in 7/39 patients, 18%), right
      and/or left ventricular dysfunction was found to be present in 5 cases (71%) and
      a pericardial effusion in 4 cases (57%). CONCLUSIONS: Myocarditis is
      underdiagnosed ante-mortem. A high index of clinical suspicion is mandatory for
      prompt diagnosis and treatment of this fatal disease seen also in the young.

PMID- 15568601
TI  - Ebstein's anomaly and pregnancy: a case report.
AB  - Ebstein's anomaly, an uncommon malformation of the tricuspid valve, has an
      extremely variable natural history, depending on a wide spectrum of pathological
      features. We here described a case of a patient with Ebstein's anomaly who gave
      birth to 2 healthy unaffected full-term infants after two successful pregnancies;
      a third pregnancy miscarried at the 11th week. The anomaly was diagnosed during
      childhood, was not associated with other cardiac anomalies, cyanosis or
      preexcitation and the echocardiographic degree of severity was low (grade 1). All
      of these factors are considered predictors of a good survival and prognosis.
      During the pregnancies, no arrhythmias, cyanosis or signs of cardiac failure were
      observed and the patient's NYHA functional class (1) remained unchanged. Our case
      is the only published case of two successful term pregnancies in Ebstein's
      anomaly, it confirms the importance of echocardiographic evaluation and that the
      probability of maternal and neonatal events may be predicted from the baseline
      characteristics of the mother. Pregnancy is well tolerated in the absence of
      important maternal cardiomegaly, cyanosis and arrhythmias and in those patients
      with mild cardiac dysfunction as evaluated at echocardiography and a low NYHA
      class, but it is associated with an increased risk of abortions and prematurity.

PMID- 15568602
TI  - Transvenous cardioverter-defibrillator implantation with a double coil lead via
      persistent left superior vena cava.
AB  - A dual-coil defibrillation lead was inserted in a 64-year-old male through a
      persistent left superior vena cava draining into the coronary sinus. The lead,
      connected to a cardioverter-defibrillator (ICD) implanted in the left pectoral
      area, was looped in the right atrium positioning the proximal and distal lead
      coils in the coronary sinus and right ventricular outflow track respectively and
      resulting in a low and stable defibrillation threshold. Because of its relative
      ease and effectiveness, this procedure may be recommended in patients with
      persistent left superior vena cava requiring an ICD implant.

PMID- 15568603
TI  - Sequential biventricular resynchronization optimized by myocardial strain rate
      analysis: a case report.
AB  - We report the case of a patient with severe left ventricular systolic dysfunction
      and left bundle branch block in whom cardiac resynchronization therapy (CRT) was
      optimized by tissue Doppler imaging. A horizontal mechanical asynchrony index was
      derived from tissue Doppler regional longitudinal strain rate profiles as the
      time difference at the onset of shortening between septum, lateral, anterior and
      inferior walls. The interventricular delay was modulated in order to achieve the
      smallest asynchrony index; on the basis of this parameter a sequential (S)-CRT
      with a left ventricular pre-excitation of 20 ms was definitively programmed. This
      optimized S-CRT was followed by an acute improvement in systolic cardiac
      performance and by a long-term (12 months) clinical benefit as well as by a
      documented decrease in LV chamber size due to a true reverse remodeling effect.
      Thus, in some patients S-CRT may be more effective than conventional CRT. Tissue
      Doppler-derived strain rate analysis can provide information on the degree of
      left intraventricular asynchrony allowing the modulation of a tailored
      interventricular delay.

PMID- 15568604
TI  - Reoperations in patients with patent left internal mammary artery.
AB  - In the past decade the rate of reoperative coronary bypass grafting has averaged
      8%. In these patients adequate myocardial protection is often difficult because
      delivery of cardioplegia is frequently suboptimal when the internal mammary
      artery graft is patent. We describe a simple technique for performing cardiac
      reoperation in patients with a patent left internal mammary artery graft through
      a balloon catheter used for angioplasty and positioned in the left internal
      mammary artery graft. Our study included 3 patients and there were no operative
      deaths and complications.

PMID- 15568605
TI  - [Atrial standstill: a paralysis of cardiological relevance].
AB  - Atrial standstill is a rare arrhythmogenic condition characterized by the absence
      of electrical and mechanical activity in the atria, transient or persistent, and
      complete or partial. It can be "idiopathic", sporadic or familial, or secondary
      to Ebstein's anomaly, Emery-Dreifuss muscular dystrophy (X-linked), Kugelberg
      Welander syndrome (autosomal recessive), and amyloidosis. Idiopathic familial
      atrial standstill is inherited as autosomal dominant trait with variable
      penetrance. To date, a few cases of familial forms of primary atrial standstill
      have been described. In each family, the number of affected members was small and
      limited to relatives of one generation. The genetic basis for familial atrial
      standstill is unknown. Recently a mutation in the cardiac sodium channel gene
      SCN5A associated with relatively rare genotypes for two connexin 40 polymorphisms
      has been reported. The diagnosis relies on the ECG demonstration of bradycardia,
      absence of P waves, and junctional narrow complex escape rhythm. Nearly 50% of
      patients suffer from Adams-Stokes attacks. In the primary persistent form, the
      atrial paralysis is paralleled by atrial dilation, mitral valve incompetence, and
      thrombotic complications, with high risk of thromboembolic complications. The
      treatment is addressed to the thromboembolic risk (anticoagulation), mitral
      incompetence (diuretics and vasodilators) and syncope (pacemaker implantation).

PMID- 15568606
TI  - [The role of transesophageal echocardiography in the assessment of the embolic
      risk during infective endocarditis: a critical review].
AB  - Embolic events are a frequent and life-threatening complication of infective
      endocarditis. This review is focused on the role of echocardiography, especially
      transesophageal echocardiography, in predicting embolic events and in the
      clinical and therapeutic management of patients with infective endocarditis.

PMID- 15568607
TI  - [Assessment of cardiovascular risk in hypertensive patients: comparison among
      scores].
AB  - At present, a correct and thorough risk evaluation represents the best prognostic
      and therapeutic approach for hypertensive patients. Recent European and American
      guidelines recommend a global stratification of the cardiovascular risk of
      hypertensive patients, based on the evaluation of risk factors, organ damage, and
      the clinical conditions associated with hypertension. A similar approach uses
      numerical risk scores that transform the percentage risk, calculated from large
      populations, into absolute values. These scores have been calculated by different
      research groups and scientific organizations with the aim of better defining the
      real risk of a given population over time. Many of these risk scores have been
      conceived by American and European scientific groups on the basis of the
      epidemiology of different risk variables in the respective populations; in
      general, north American hypertensives are exposed to a higher cardiovascular risk
      compared to Europeans and some European countries have a higher risk than others.
      The present review underlines the pivotal role of a correct risk evaluation of
      hypertension as reported in the guidelines. We briefly analyze the principal
      studies on risk scores: we compare the advantages and disadvantages of the
      different scores, as well as the similarities and differences, in order to
      demonstrate not only their utility, but also the possible equivalence of the
      different parameters considered.

PMID- 15568608
TI  - [New perspectives for anticoagulation in non-rheumatic atrial fibrillation: oral
      antithrombins].
AB  - Non-rheumatic atrial fibrillation (NRAF) is one among the major public health
      problems, because it is associated with a high incidence of stroke or systemic
      thromboembolism. Warfarin significantly reduces cerebral/systemic events mainly
      in high-risk patients; unfortunately such drug is often as well under-used in
      eligible patients as under-dosed in treated patients. Traditional therapy with
      oral anticoagulants has several disadvatages: narrow therapeutic window, and
      often unpredictable dose-response so that frequent monitoring of the INR is
      required. It is therefore crucial that patients preferences and education be
      integrated into the decision-making process. Physicians often underprescribe oral
      anticoagulants since they perceive the risk of major bleeding as unacceptable
      because of some well known risk factors (e.g. previous bleedings, severe
      hypertension), and of qualms about drug interactions or alleged poor compliance.
      Therefore, the development of easy-to-use antithrombotic agents is still a
      challenge. New agents such as oral direct thrombin inhibitors are going to hold
      the promise for the next future. Ximelagatran is an orally active small molecule;
      being the first new oral anticoagulant used in large clinical trials. This
      molecule has many advantages in comparison to warfarin, such as the rapid
      onset/offset of action, the fixed oral dose, the no need of dose adjustment or of
      anticoagulation monitoring, as well the lack of food/alcohol intake interference
      as of drug interactions. The SPORTIF III and V trials have shown that
      ximelagatran is not inferior to warfarin in the prevention of strokes in patients
      with NRAF (both persistent and paroxysmal), but a side effect--consisting in the
      significant elevation of liver enzymes (> 3 times the upper limit of normal) in
      6% of patients--was found. Further randomized trials are clearly needed, while
      current data suggest that ximelagatran will be able to represent a future viable
      therapeutic option for prevention of thromboembolism in patients with NRAF,
      offering huge advantages with respect to classic oral anticoagulants.

PMID- 15568609
TI  - [Statistical notes. From superiority to non-inferiority clinical trials: a leap
      in the dark?].
AB  - In these "statistical notes", equivalence and non-inferiority randomized
      controlled clinical trials (RCCT) are considered. Equivalence trials are designed
      to confirm the absence of a meaningful difference between the effect of two
      treatments. Non-inferiority trials are designed to prove that the new treatment
      is no less effective than an existing one: it may be more effective or it may
      have a similar effect. In this note the attention is addressed to suitable
      criteria for the choice of the tolerance margin epsilon, i.e. the largest
      difference which is clinically acceptable, so that a difference bigger than that
      would matter in practice. In particular, the procedures for the determination of
      the margin epsilon, used by the authors of the non-inferiority RCCT COBALT and
      INJECT, are presented and discussed in detail. The ethical implications of
      equivalence and non-inferiority RCCT are here considered and the reader is
      repeatedly invited to consider the appropriateness of the basic arguments
      asserted by the supporters of this kind of studies.

PMID- 15568610
TI  - [Prognostic value of high-density lipoproteins in the cardiology unit].
AB  - BACKGROUND: Clinical and epidemiological studies have shown an inverse and
      independent association between high-density lipoproteins (HDL) and risk of
      developing coronary artery disease. The aim of this study was to estimate the
      prevalence of the phenotype characterized by low HDL values and to assess the
      impact of HDL plasma levels on the prognosis of patients hospitalized in the
      cardiologic unit of our Institute, during 30 months of follow-up. METHODS:
      Between February 1999 and February 2002, 1169 patients (778 men and 391 women)
      who had undergone hospitalization, were enrolled in a cardiovascular registry.
      The lipid profile was evaluated for all patients; a subgroup (n = 626) underwent
      coronary angiography. Patients were followed up for a mean period of 30 months,
      during which the frequency of revascularization procedures (coronary angioplasty
      or bypass), myocardial infarction and death were recorded. RESULTS: Nearly half
      of the subjects (45%, of which 77% men) showed HDL values < 40 mg/dl, and 25% of
      the population (80% men) were characterized by extremely reduced HDL
      concentrations (< or = 35 mg/dl). Patients with coronary atherosclerosis showed
      HDL levels lower than those of subjects with negative angiography (41.0 +/- 10.8
      vs 46.6 +/- 10.9 mg/dl, p < 0.0005). An inverse relationship was found between
      HDL and coronary artery disease: the risk of developing the illness decreased by
      4% for each increase of 1 mg/dl in HDL (p < 0.005); in males < 60 years and
      females < 65 years, the coronary artery disease risk association increased by 3%
      (p < 0.005). The risk of interventions decreased by 2% for each increase of 1
      mg/dl in HDL (p < 0.01), both in the total population and in males < 60 years and
      females < 65 years. Finally, patients with HDL < 40 mg/dl showed a higher risk of
      revascularization interventions (+25%, p < 0.01) in comparison to the subjects
      with HDL > 40 mg/dl. CONCLUSIONS: This study demonstrates: a) the high prevalence
      of the phenotype characterized by low plasma concentrations of HDL among patients
      hospitalized in a cardiologic unit; b) lower HDL values in subjects with coronary
      atherosclerosis compared to subjects with normal coronary angiography; c) the
      inverse relationship between HDL and coronary atherosclerosis; d) the prognostic
      value of HDL as a predictor of surgical revascularization.

PMID- 15568611
TI  - [Off-pump endovascular treatment of aortic arch aneurysms].
AB  - BACKGROUND: Traditional repair of aortic arch aneurysms requires cardiopulmonary
      bypass, hypothermia and circulatory arrest. Endovascular repair is an attractive,
      less invasive alternative that may change our therapeutic approach. The aim of
      this study was to review our clinical experience with endovascular treatment of
      aortic arch aneurysms and to address the new problems in this area. METHODS: In
      the last 5 years, we treated 21 patients for aortic arch pathology with an "off
      pump" endovascular repair (18 men, 3 women, mean age 71.4 +/- 7.2 years). We used
      26 stent grafts (5 Gore Excluder TAG, 3 Endomed Endofit, 6 Medtronic Talent, 12
      Cook Zenith TX1) with a mean of 1.2 graft/patient. Proximal fixation of endograft
      was achieved by means of aortic "de-branching" in 11 cases. In 10 cases the left
      subclavian artery was intentionally covered without revascularization. Follow-up
      included clinical examination, chest X-ray and computed tomography at discharge
      and at 6-month intervals thereafter. RESULTS: Technical success was 85% (18/21).
      There was one in-hospital death (4.7%) due to endograft migration. We observed 2
      cases of type I endoleak (9.5%). One surgical conversion was performed 2 weeks
      after the procedure, because of total collapse of the stent graft with rupture of
      three stents. No complications related to the coverage of the left subclavian
      artery were observed. At a mean follow-up of 18.7 +/- 12.8 months, no mortality
      or morbidity including new-onset endoleak, stent-graft migration and thrombosis
      of supra-aortic grafts were recorded. CONCLUSIONS: Endovascular treatment of
      aortic arch pathology is feasible even in elderly patients. However, accurate
      placement in the arch and aneurysm sealing with the currently available devices,
      may be challenging due to the involvement of supra-aortic vessels, the anatomical
      curvature of the arch, the high blood flow, and substantial movement of the aorta
      with each heartbeat.

PMID- 15568612
TI  - [Long QT and torsade de pointes in a patient with acquired human immunodeficiency
      virus infection in multitherapy with drugs affecting cytochrome P450].
AB  - In acquired human immunodeficiency virus (HIV) infection, a long depolarization
      period at ECG may be the consequence of cardiac complications due to viral
      myocarditis or cardiomyopathy or indirectly due to autonomic neuropathy, or
      sometimes resulting from pharmacological treatments. Several drugs administered
      for direct treatment of HIV disease or its complications, such as antiretrovirus,
      fluconazole, and antibiotics, may induce ventricular arrhythmias due to long QT
      prolonged depolarization period. Also methadone, frequently associated with HIV
      therapy to treat patients with opiate addiction, is described in the literature
      to have cardiac inotropic effects. It has also the potential to increase the QT
      period and to develop ventricular torsade de pointes, primarily through
      interference with the rapid component of the delayed rectifier potassium ion
      current. Moreover, the use of methadone associated with other inhibitors of
      cytochrome P450 might increase plasma concentrations and contribute to methadone
      cardiac toxicity. We report the case of an HIV patient receiving antiretroviral
      treatment, fluconazole and high-dose methadone, who suddenly complained of
      vertigo, dizziness, pre-syncope and syncope due to severe ventricular arrhythmias
      that disappeared after discontinuation of all treatments.

PMID- 15568613
TI  - [Severe aortic stenosis in the elderly and cryptogenic intestinal bleeding (Heyde
      syndrome): a case report].
AB  - The Heyde syndrome describes the association between calcific aortic stenosis and
      intestinal bleeding. The pathophysiologic link between both entities has remained
      unclear so far. In several studies the intestinal bleeding has been attributed to
      angiodysplasia of the gut, with following cessation of the bleeding after
      replacement of the aortic valve. A case report.

PMID- 15568614
TI  - [The cardiologist and the art].

PMID- 15568615
TI  - Differential effects of CD28 costimulation upon cytokine production by CD4+ and
      CD8+ T cells.
AB  - The impact of CD28 ligation upon CD4+ and CD8+ T lymphocyte proliferation and
      cytokine production was assessed. Although costimulation increased the
      proliferative response of both T cell subsets, cytokine production was most
      markedly increased in the CD4+ subset, as evidenced by a 40-fold increase in
      interleukin-2 (IL-2), a 14-fold increase in interleukin-3 (IL-3) and 5-fold
      increases in interferon gamma and GM-colony-stimulating factor (CSF) production.
      The CD8+ T cell response to CD28 ligation was less marked, maxima being a 5-fold
      increase in IL-2 production and 2-fold increases in IL-3 and GM-CSF production.
      Resolution of CD4+ and CD8+ T cells into their CD44lo (naive) and CD44hi
      (memory/effector) subsets revealed that naive CD4+ T cells were the most CD28
      responsive subsets. CD28-mediated costimulation promotes distinct differentiation
      programs in CD4+ versus CD8+ T cells.

PMID- 15568616
TI  - Prolactin modulates IL-8 production induced by porins or LPS through different
      signaling mechanisms.
AB  - Prolactin (PRL) induces cell proliferation and cell differentiation through the
      well-known mitogen-activated protein kinases (MAPKs) and Janus kinase
      (JAK)/signal transducer and activator of transcription (STAT) pathways, depending
      on the cell line. MAPKs play a central role in signaling transduction mechanisms
      that transmit mitogenic or differentiation signals from an activated receptor to
      the intracellular machinery. All of the cytokine receptors that activate the
      JAK/STAT pathway also activate the MAPK pathway. The aim of the present study was
      to delineate the signal pathways implicated in IL-8 release by THP-1 cells,
      pretreated with PRL, after stimulation with either lipopolysaccharide (LPS) or
      porins from Salmonella enterica serovar Typhimurium. PRL activates the JAK2/STAT1
      3 signaling pathway, while LPS or porins from S. enterica serovar Typhimurium
      does not induce any phosphorylation of this pathway. However, in THP-1 cells, the
      combination of PRL followed by either S. enterica serovar Typhimurium LPS or
      porins produced a greater MEK1-MEK2/MAPKs activation response than treatment with
      PRL alone. Similarly, PRL pretreatment of THP-1 cells resulted in an increase in
      IL-8 release in response to stimulation with either LPS or porins. This additive
      effect on IL-8 release was reduced when the cells were also treated with PD
      098059, a selective inhibitor of the MEK1 activator and the MAPK cascade, or
      SB203580, a specific inhibitor of the p38 pathway, or AG490, a specific JAK/STAT
      pathway inhibitor, providing evidence that there are different signal pathways
      activated which have a cumulative effect.

PMID- 15568617
TI  - Tumor immunotherapy with alternative reading frame peptide antigens.
AB  - The translation machinery of a eukaryotic cell produces errors in decoding mRNA
      that may give rise to alternative reading frame (Arf) polypeptides. We predicted
      these putative aberrant translation products from the cDNA of three tumor
      associated antigens (Ag): a transmembrane glycoprotein of the class I receptor
      tyrosine kinase erbB family HER-2, telomerase reverse transcriptase (TERT) and
      prostatic acid phosphatase (PAP). Immunization of mice with Arf peptide-pulsed
      antigen presenting cells (APC) generated potent in vivo immune protection against
      tumors expressing respective tumor-associated Ag. CD8+ T cells from mice
      immunized with HER-2 derived protective Arf peptides specifically recognized HER
      2 transfected tumor cells. The strategy described here has potential for
      designing highly efficient novel vaccines for Ag-specific immunotherapy of human
      malignancies.

PMID- 15568618
TI  - Complement component C5 is not involved in scrapie pathogenesis.
AB  - During transmissible spongiform encephalopathy (TSE) infections the accumulation
      of abnormal prion protein within the brain is often accompanied by severe
      neurodegeneration. Studies have implicated complement, including the membrane
      attack complex (MAC, C5b-C9), in inducing pathology in some neurodegenerative
      diseases. Recent studies show the MAC is localized on neurons in the brains of
      TSE patients implicating complement-mediated cell lysis in TSE neuropathology. To
      determine the role of the MAC in TSEs, we compared scrapie pathogenesis in C5
      deficient and C5-sufficient mice. C5-deficient mice developed clinical scrapie
      with incubation periods similar to C5-sufficient mice. Furthermore, the severity
      of the neuropathology was not significantly different between C5-deficient and C5
      sufficient mice. These data show that C5, and the MAC, are not involved in TSE
      pathogenesis.

PMID- 15568619
TI  - Production of hepatitis B surface antigen-pulsed dendritic cells from
      immunosuppressed murine hepatitis B virus carrier: evaluation of immunogenicity
      of antigen-pulsed dendritic cells in vivo.
AB  - Vaccines containing hepatitis B surface antigen (HBsAg) induce antibody to HBsAg
      (anti-HBs) in most normal individuals and protects them from hepatitis B virus
      (HBV) infection. However, these vaccines are not efficient at inducing anti-HBs
      in immunosuppressed individuals, especially in immunosuppressed HBV carriers. The
      aim of this study was to prepare and to assess the efficacy of a dendritic cell
      (DC)-based vaccine in an immunosuppressed HBV transgenic mouse (HBV-Tg), an
      animal model of the HBV carrier state. In order to prepare immunosuppressed HBV
      Tg, HBV-Tg were injected with FK-506, an immunosuppressive agent, once daily,
      intraperitoneally for 15 days. Spleen cells of immunosuppressed HBV-Tg expressed
      very little mRNAs for interleukin-2 and interferon-gamma. DCs were isolated from
      the spleen of immunosuppressed HBV-Tg and cultured with HBsAg (100 microg) for 48
      h to prepare HBsAg-pulsed DCs. Immunosuppressed HBV-Tg expressing HBsAg in the
      sera were administered with HBsAg-pulsed DCs or unpulsed DCs or HBsAg in adjuvant
      for different durations. Immunosuppressed HBV-Tg (n = 8) twice administered with
      HBsAg-pulsed DCs expressed anti-HBs in the sera within 6 weeks of first
      injection. Seven of eight immunosuppressed HBV-Tg remained positive for anti-HBs
      in the sera for the next 12 weeks of observation in spite of receiving daily
      injection of FK-506 for the entire duration. However, immunosuppressed HBV-Tg
      administered with unpulsed DCs or HBsAg in adjuvant did not express anti-HBs in
      the sera. The data show that DCs from immunosuppressed HBV-Tg can be loaded with
      HBsAg to prepare immunogenic HBsAg-pulsed DCs. HBsAg-pulsed DCs induced anti-HBs
      in immunosuppressed HBV-Tg. This approach may be of use to induce and maintain
      anti-HBs in immunosuppressed human HBV carriers.

PMID- 15568620
TI  - Molecular basis for complement component 6 (C6) deficiency in rats and mice.
AB  - Complement component C6 is a part of the lytic membrane attack complex formed
      during complement activation. Animal modeling to define the role of C5a vs. C5b-9
      in human disease has used rodents deficient in C6, yet the molecular basis for
      the deficiencies has not been ascertained. Oligonucleotides derived from a 493 bp
      EST sequence of the rat C6 gene were used to isolate full-length transcripts of
      rat C6 mRNA. Sequence analysis confirmed that the derived amino acid sequence for
      rat C6 is highly homologous to human and mouse. We identified a 31 bp deletion in
      exon 10 of the C6 gene that leads to C6 deficiency in a strain of PVG rats (PVG/c
      ) and developed a PCR-based genotyping test. In addition, we identified four
      point mutations in the mouse C6 gene that may result in C6 deficiency observed in
      the Peru-Coppock mouse strain. A serendipitous finding from this study was a
      coagulation defect in the C6 deficient mice and rats. C6 deficient mice or rats
      demonstrated prolonged tail bleeding times that was reversed by treatment with
      purified rat C6 protein. Further, adenosine diphosphate induced platelet
      aggregation were markedly reduced in C6 deficient rats. The molecular basis for
      these coagulations defects is unknown at present.

PMID- 15568621
TI  - Immunology of human endometrium.
AB  - In pregnancy, the endometrium represents the hosting surface for invading semi
      allogeneic cells. A very fine tuning of cellular interactions is indispensible
      for the successful symbiosis of mother and fetus. Such interactions include a
      variety of immune cells, which are present in extremely high concentrations, and
      trophoblast cells. A wide spectrum of soluble and surface molecules is involved
      in homing, activation and switching of lymphocyte functions, but also in
      regulation of embryo implantation and control of trophoblast invasion. This mini
      review provides a brief overview of immunological features of the endometrium.

PMID- 15568622
TI  - [Missed acute compartment syndrome of the lower leg].
AB  - After some considerable delay, acute compartment syndrome of the lower leg was
      diagnosed in a 17-year-old man, a 32-year-old man and a 76-year-old woman. The
      first patient was an accident victim whose leg was continuously bandaged for
      three days following treatment of a complicated femur fracture and lower leg
      wounds, so that inspection was not possible. In the second patient who was also
      an accident victim, the haemodynamics and the neurological condition initially
      required so much attention that the compartment syndrome was only noticed after
      48 hours. The woman presented with a cold, painful left foot. She had atrial
      fibrillations. A thrombus mass was removed endovascularly from the femoral
      artery. She controlled her own pain medication by means of an epidural catheter,
      but as a result of that a reperfusion compartment syndrome was only noticed at a
      later stage. These cases reveal that it can be very difficult to establish the
      diagnosis of acute compartment syndrome, especially if this is masked by the
      already quite subjective symptoms of the clinical picture. The consequences of a
      missed compartment syndrome are serious, with a considerable impairment of the
      limb concerned that often necessitates amputation. Awareness and healthy
      suspicion are the keys to a quick and timely diagnosis. Prophylactic fasciotomies
      must be carried out on the basis of several clear indications.

PMID- 15568623
TI  - [Brain injury in boxers and soccer players; an advisory report from the National
      Health Council of the Netherlands].
AB  - The National Health Council of the Netherlands has released a report entitled
      'Brain damage in boxers and soccer players'. It examines epidemiology and
      prevention of cerebral damage from professional and amateur sports, focusing
      particularly on soccer and boxing. The connection between cerebral injuries and
      acute and chronic sports injuries is well established. However, proper diagnosis
      and therapy may be difficult in acute head trauma and during the chronic stage.
      It makes proposals for a simple cognitive screening test for acute injuries
      (soccer-related in particular) and more extensive testing for the detection and
      follow-up of chronic cerebral injuries (boxing-related in particular).
      Neuropsychological testing may be an important additional diagnostic tool.
      Professional boxing should be banned if the measures suggested fail to prevent
      chronic cognitive dysfunction. A dedicated knowledge centre for soccer and boxing
      would enhance the epidemiology and knowledge of brain injuries, and could help to
      develop more evidence-based guidelines in the future.

PMID- 15568624
TI  - [The practice guideline 'Stable angina pectoris' (second revision) from the Dutch
      College of General Practitioners; a response from the perspective of general
      practice].
AB  - The Dutch College of General Practitioners' (Dutch acronym: NHG) practice
      guideline 'Stable angina pectoris' (second revision) provides clear guidelines
      for the diagnosis and treatment of patients who experience chest pains as a
      result of angina pectoris, especially if coronary artery disease is the
      underlying cause of the complaints. The practice guideline clearly indicates for
      which complaints the general practitioner should suspect angina pectoris and
      which information from the anamnesis, family history and risk factors can
      contribute to distinguishing between stable and unstable angina pectoris.
      However, the physical examination should not be omitted because this can provide
      important indications for coronary or pulmonary dysfunction. According to the
      practice guideline, the treatment policy is determined by the estimated risk of
      significant coronary artery disease. However, additional tests can be useful even
      in the case of a small risk, as these can reassure patients. The indications and
      contraindications for medicinal substances are clearly presented.

PMID- 15568625
TI  - [The practice guideline 'Stable angina pectoris' (second revision) from the Dutch
      College of General Practitioners; a response from the perspective of cardiology].
AB  - The Dutch College of General Practitioners (Dutch acronym: NHG) practice
      guideline 'Stable angina pectoris' (second revision) provides a clear insight
      into the anamnesis, diagnosis and treatment of patients with stable angina
      pectoris. However, we would like the guideline to include more information about
      the indication areas for additional tests: these tests can also be useful for
      patients with less than a 30% risk or more than a 70% risk of significant
      obstructive coronary disease. The same applies for an exercise ECG or possible
      pharmacological stress tests for patients with ischaemia during rest or a left
      bundle branch block. Further, angiotensin-converting enzyme inhibitors can be
      effective as a form of secondary prevention among patients with stable angina
      pectoris who also have diabetes mellitus and/or a reduced left ventricular
      function.

PMID- 15568626
TI  - [Preconditions for a stay in high altitude areas in the case of existing health
      problems].
AB  - Various symptoms can arise during a stay in high altitude areas (above 2500 m),
      such as tissue hypoxia and in particular pulmonary and brain oedema. Patients
      with existing health problems can expect to develop more complaints or more
      severe complaints at an earlier stage. For a number of these patients a stay in
      high altitude areas should be advised against or should only take place if
      certain measures are taken. The advising physician should have knowledge about
      the reactions of the human body on hypoxy, and about (derailments of) the
      acclimatisation proces in high altitude areas. Every patient with a disease that
      can interfere with hypoxia should be assessed on an individual basis. The most
      important absolute and relative contraindications are cardiac and pulmonary
      conditions, haemoglobin abnormalities, diabetes mellitus, hypertension, epilepsy,
      severe obesity, kidney diseases and pregnancy. In the case of an existing health
      problem, a stay in high altitude should only be considered if medical care can be
      quickly and adequately provided on the spot.

PMID- 15568627
TI  - [Summary of the practice guideline 'Stable angina pectoris' (second revision)
      from the Dutch College of General Practitioners].
AB  - Typical angina pectoris is characterised by retrosternal complaints that are
      provoked by exertion, cold, emotional stress or heavy meals and are relieved by
      rest within 15 minutes or within a few minutes of using sublingual nitroglycerin.
      If 2 or 3 of these symptoms are present then the term 'atypical angina pectoris'
      is used. The general practitioner can estimate the risk of significant coronary
      artery disease on the basis of the anamnesis. Additional diagnostics in the form
      of an exercise ECG is only worthwhile if the pretest probability of coronary
      artery disease lies between 30% and 70% (atypical angina pectoris) and not if the
      diagnosis is extremely likely or extremely unlikely. Patients with angina
      pectoris should be informed about the alarm symptoms which can be indicative of
      unstable angina pectoris or acute myocardial infarction. Sublingual nitrate
      therapy is used for the short-term control of angina. If more than 2 attacks per
      week occur, a maintenance treatment consisting of beta-blockers, nitrates, or
      calcium channel blockers should be started in this order of preference. For
      secondary prevention, acetylsalicylic acid and statins should be prescribed and
      lifestyle advice should be given, such as smoking cessation, sufficient physical
      exercise and a healthy diet.

PMID- 15568628
TI  - [Diagnostic image (214). A young man with a thoracic trauma].
AB  - In a 16-year-old man who sustained severe blunt thoracic trauma, pulmonary
      contusion with multiple pneumatoceles was observed.

PMID- 15568629
TI  - [Prevalence of parental behaviour to diminish the crying of infants that may lead
      to abuse].
AB  - OBJECTIVE: To estimate the prevalence of parental actions to stop infant crying
      that may threaten infant health, and to determine specific risk groups regarding
      these actions. DESIGN: Descriptive. METHOD: Before their visit to a well-baby
      clinic in the Netherlands, parents of 3345 infants aged 1-6 months (96.5%
      response) filled out an anonymous questionnaire on actions that they undertook to
      stop their child crying. RESULTS: At 6 months, 5.6% (95% confidence interval: 4.2
      7.0%) of all the parents reported having smothered, slapped, or shaken their
      infant at least once because of its crying. The highest risks for detrimental
      parental actions were run by infants of parents from non-industrialised
      countries, of parents with no or only a part-time job, and of parents who had
      judged their infant's crying as excessive. CONCLUSION: Clinicians should be aware
      of the observed risk factors for abuse of young children known to cry a lot, in
      order to help parents to cope with this crying.

PMID- 15568630
TI  - [Acute compartment syndrome of the foot].
AB  - In two patients, a girl aged 2 and a man aged 52 years, who had suffered a severe
      crush trauma, acute compartment syndrome of the foot was diagnosed. Decompression
      by means of one medial and two dorsal dermato-fasciotomy incisions was carried
      out and fractures of the metatarsals were repaired using K-wires. The girl
      recovered completely, but the man developed progressive necrosis in the flexors
      of the foot and on the skin on the foot sole which necessitated amputation of the
      foot. Acute compartment syndrome of the foot is an uncommon disease and is mainly
      characterised by extreme pain and often diffuse swelling of the foot. It is a
      serious threat to the foot which can lead to severe long-term complications
      including contractures, deformity and paralysis. Compartment syndrome of the foot
      is a primary clinical diagnosis. When in doubt, direct pressure measurement of
      the foot compartments should be done by means of needle catheterisation. If
      compartment pressure exceeds 30 mm Hg, acute dermato-fasciotomy of all nine
      compartments is indicated. A combined medial and dorsal approach is adopted to
      release the foot compartments; three incisions are usually sufficient. If
      fractures are present, these are repaired at the same time. Within four hours an
      unnoticed compartment syndrome can lead to irreversible ischaemia of the nerves
      and muscle tissue with long-term irreversible consequences.

PMID- 15568631
TI  - [The acute compartment syndrome of the arm].
AB  - Two 37-year-old men, both drug addicts, and a 32-year-old homeless woman
      presented themselves with a painful arm. Except for the first patient, there was
      a delay in diagnosing the compartment syndrome of the arm. In the first patient
      emergency fasciotomy led to a good functional recovery, however kidney function
      was lost despite proper treatment, possibly due to combined heroine use and
      muscle breakdown. In the second patient prolonged immobility and altered
      consciousness by drug use should have increased clinical suspicion. Poor arm
      function remained even after fasciotomy. In the third patient inadequate clinical
      examination delayed surgery. Major early symptoms of compartment syndrome are
      progressive disproportional pain and sensory loss, not relieved by analgesia. If
      left untreated, the ischaemic tissue damage is potentially limb and even life
      threatening. The acute compartment syndrome is a clinical diagnosis and a low
      threshold for surgical exploration and fasciotomy is advocated.

PMID- 15568632
TI  - [The surgical treatment of nonpalpable breast carcinoma in a university teaching
      hospital and a general teaching hospital by residents-in-training and surgeons;
      comparable results].

PMID- 15568633
TI  - [Long acting insulin analogs: possibly more stable glucose regulation].

PMID- 15568634
TI  - [Long-acting insulin analogs: progressing slowly].

PMID- 15568635
TI  - [Endoscopic, pathologic-anatomic and histologic findings in the bovine teat. 1.
      Changes in the area of the teat cistern in slaughtered cows].
AB  - In the present study 795 teats of slaughtered cows were examined endoscopically.
      Teats which showed lesions were examined histologically. Abnormalities were
      detected endoscopically in 37 teats. In five cases red discolorations were
      observed. Histologically these alterations proved to be fresh bleedings within
      the fibromuscular layer of the teat cistern. Thirteen teats showed yellowish
      discolorations of the cistern surface. Three of these cases could not be cleared
      up histologically. In the other cases moderate or severe blood pigment deposition
      (n = 10) or severe fibrosis (n = 3) of the fibromuscular layer were found.
      Neither fresh bleeding nor severe blood pigment deposition was found in teats
      with normal coloured epithelium of the cistern. Cistern surface was smooth in 18
      cases, whereas in 19 cases nodules were found. Histologically all nodules
      consisted of fibrovascular tissue ("granulation tissue") covered with cisternal
      epithelium. Detailed histological examinations, however, revealed considerable
      morphological variations regarding the overlying epithelium, the extent and kind
      of cellular infiltration, the extent of angioplasia and fibroplasia as well as
      fresh bleedings or deposition of blood pigment in the underlying fibrovascular
      tissue in some cases. It was concluded, that teat endoscopy enables a
      differentiation between fresh and old bleedings according to the coloration of
      the cisternal surface. Nodular proliferations of the cistern surface generally
      consists of fibrovascular ("granulation") tissue. Further histological details,
      however, and thus possible information about the pathogenesis of the lesions
      cannot be assessed endoscopically.

PMID- 15568636
TI  - [The occurrence of Coxiella burnetii in sheep and ticks of the genus Dermacentor
      in Baden-Wuerttemberg].
AB  - This study examined the occurrence of Coxiella burnetii (C. burnetii), the
      infectious agent of Q-fever, in sheep and sheep-ticks in Baden-Wuerttemberg,
      Germany, as a possible source of infection in Q-fever outbreaks. Using PCR, we
      examined a total of 1066 Dermacentor ticks from 23 herds and 49 samples of tick
      excrement from 18 herds for C. burnetii. We found the infectious agent in one non
      engorged tick and in one sample of tick excrement from the same herd, in Efringen
      Kirchen (district Loerrach). Sequencing the PCR-products confirmed the
      amplifications as specific for C. burnetii. Further serological tests of random
      samples of the four districts of Baden-Wuerttemberg showed a seroprevalence from
      0 to 1.4% using complement fixation test (CFT), as well as a 0.9 to 10.2%
      seroprevalence, using ELISA test. Serum samples from a Q-fever-suspicious herd
      resulted, however, in 6% (CFT) and 53% (ELISA) positive reactions. A comparison
      between CFT and ELISA showed both a correlation of the two test methods that
      increased with higher CFT titration levels and positive reactions using ELISA for
      9.4% of the serums that had tested negative using CFT. The results of the present
      study reveal that ticks and their excrements are important vectors of
      transmission of Q-fever in Baden-Wuerttemberg. Investigations on C. burnetii
      using PCR as well as serological surveys of sheep are important instruments for
      diagnosis and disease control of Q-fever.

PMID- 15568637
TI  - [Use of copper oxide wire particles (Copinox) for the prevention of congenital
      copper deficiency in a herd of German Improved Fawn breed of goat].
AB  - In a herd of German Improved Fawn breed of goat in the year 2000 neonatal kid
      losses due to congenital copper deficiencies were observed. To clarify the
      problems and to prevent losses in the next breeding season serum copper levels of
      10 dams and four control Boer goats were investigated at four time points during
      one year. Additionally ten kids of the following year were sampled and the serum
      copper levels were studied. Immediatly after parturition and 8 weeks later the
      dams showed low serum copper levels (10.4 +/- 11.1 micromol/l, 5.7 +/- 2.9
      micromol/l resp.). At the end of the pasture season an increase of serum copper
      could be measured (19.3 +/- 16.0 micromol/l). To prevent enzootic ataxia due to
      congenital copper deficiency, the dams were treated with copper oxide wire
      particles in the next late gestation. At this time point serum copper
      concentrations started to decrease (18.5 +/- 8.4 micromol/l). The re-examination
      3 month later demonstrated an increase of the serum mean copper concentrations up
      to 23.4 micromol/l in the dams and to 16.2 micromol/l in the kids. The serum
      copper levels were significantly higher compared to the levels the year before.
      Big variation of the serum copper levels in the control Boer goats occurred
      during the year, but no clinical symptoms of copper deficiency could be observed.
      The copper levels in the grass and soil samples were 6.8 mg/kg and 0.2 mg/kg dry
      substance, respectively. A secondary copper deficiency based on cadmium could be
      excluded through the low levels of soil samples. The contents of sulphur and
      molybdenum were not determined. The results indicate that the German Improved
      Fawn breed of goats suffered from a primary copper deficiency due to the
      inefficient mineral supplementation. The administration of Copinox in the last
      third of the gestation leads to a continious raising of the copper concentrations
      in the serum and is suited to prevent ataxia due to congential copper deficiency
      in neonatal kids.

PMID- 15568638
TI  - Husbandry management, worm control practices and gastro-intestinal parasite
      infections of sows in pig-breeding farms in Munsterland, Germany.
AB  - A cross-sectional survey was performed on 144 farms randomly selected from 3
      breeding organisations in Munsterland, Germany, to obtain representative data on
      husbandry management, worm control practices and their possible associations with
      gastro-intestinal parasite infections in sows. Straw bedding was provided in the
      majority of gestation units; lactating sows were frequently kept strawless.
      Pasturing of gilts and non-lactating sows were performed in 37% of the farms.
      Sows were treated with anthelmintics (mainly benzimidazoles, ivermectin or
      levamisole) in 98% of the farms. The proportions of farmers performing the
      'targeted' (mainly prefarrowing) or 'non-targeted' treatment strategy (treatment
      of all animals several times per year) were similar. Piglets were
      anthelmintically dosed in only 19% of the farms. Patent infections of sows with
      Oesophagostomum spp., Ascaris suum, Trichuris suis and Eimeria spp. were detected
      in 79%, 7%, 8% and 29% of all the farms, respectively. Hyostrongylus rubidus
      infections were only found in farms with pasturing. The within-farm prevalences
      of both the strongylid and Eimeria infections were negatively correlated with the
      herd size but positively with the weaning age. Risk factors for strongylid
      infections were straw bedding in pens and pasturing. Pasturing was a risk factor
      for Eimeria infections too. There was a positive association between the time
      interval to last deworming of sows and strongylid egg counts. However, neither
      the treatment strategy nor the anthelmintic class used was associated with
      nematode infections. No relations were found between different cleaning methods
      in stables and endoparasite infections.

PMID- 15568639
TI  - [Arthrogryposis associated with facial scoliosis and torticollis in German
      Holstein calves].
AB  - In 13 German Holstein calves from two different dairy farms arthrogryposis of the
      front legs, facial scoliosis and torticollis were observed. Obvious environmental
      reasons could not be found. Chromosomal anomalies in two affected calves were not
      detectable. A striking feature was the high frequency of affected calves among
      the offspring of one natural service sire. A plausible explanation of the
      congenital anomalies observed is a dominantly inherited mutation restricted to
      germ cells.

PMID- 15568640
TI  - Topical tea tree oil effective in canine localised pruritic dermatitis--a multi
      centre randomised double-blind controlled clinical trial in the veterinary
      practice.
AB  - Tea tree oil, a volatile oil, is well known for its broad antibacterial and
      antifungal activity. A standardised and stabilised 10% tea tree oil cream was
      tested against a commercial skin care cream (control cream) in the management of
      canine localised acute and chronic dermatitis. Fifty-seven dogs with clinical
      manifestations of mostly pruritic skin lesions or alterations, skin fold
      pyodermas and other forms of dermatitis, corroborated by predominantly positive
      fungal and bacterial skin isolates, were enrolled by seven practising
      veterinarians and randomly allocated to two study groups (28:29) and were treated
      twice daily with a blinded topical preparation. After 10 days of treatment,
      success rates of 71% for the tea tree oil cream and 41% for the control cream
      (over-all efficacy documented by the veterinary investigator) differed
      significantly (p = 0.04), favouring tea tree oil cream treatment. Accordingly on
      day 10, the tea tree oil cream caused significantly faster relief than the
      control cream (p = 0.04) for two common clinical dermatitis signs, pruritus
      (occurring in 84 % of dogs) and alopecia. Only one adverse event was reported in
      the tea tree oil group (suspected not to be causally related to the study drug)
      and none in the control cream group. The tested herbal cream appears to be a fast
      acting safe alternative to conventional therapy for symptomatic treatment of
      canine localised dermatitis with pruritus.

PMID- 15568641
TI  - [Correlation between Salmonella typhi incidence in humans and the degree of
      infection in street pigeon flocks].

PMID- 15568642
TI  - PDA students.

PMID- 15568643
TI  - Devonport incident and the subsequent Clothier inquiry.

PMID- 15568644
TI  - Strengths and limitations of the model virus concept.
AB  - New plasma- or cell culture-based pharmaceutical manufacturing processes must be
      validated for their ability to eliminate potentially contaminating pathogens. To
      evaluate the virus elimination potential of such a process, current guidelines
      propose the use of model viruses. This approach is discussed based on two
      examples. These examples show the strengths of this approach but also its
      limitations. The blood processing industry was recently challenged by the
      emergence of a West Nile Virus (WNV) epidemic in the United States. The
      susceptibility of WNV and a frequently used model virus to commonly used
      inactivation methods is compared. Current data show a good correlation. Due to
      its physico-chemical properties and the high viremic titers, B19 virus (B19V), a
      small (diameter 18-26 nm), robust, non-enveloped parvovirus, is a considerable
      challenge for the plasma processing industry. Mice minute virus (MMV), an animal
      parvovirus, is used as a model for B19V. Data show that B19V is considerably more
      susceptible to some physico-chemical inactivation methods than MMV. The examples
      of WNV and B19V show that the model virus concept is a practicable tool to
      evaluate the safety of plasma- or cell culture-derived pharmaceuticals regarding
      known and emerging viruses. It also underlines the need for investigational
      studies of relevant viruses if they can be handled in a normal virology
      laboratory, under moderate biosafety conditions.

PMID- 15568645
TI  - Drying effects on residual moisture of lyophilization rubber closures.

PMID- 15568646
TI  - Environmental monitoring: data trending using a frequency model.
AB  - Environmental monitoring programs for the oversight of classified environments
      have used traditional statistical control charts to monitor trends in microbial
      recovery for classified environments. These methodologies work well for
      environments that yield measurable microbial recoveries. However, today
      successful increased control of microbial content yields numerous instances where
      microbial recovery in a sample is generally zero. As a result, traditional
      control chart methods cannot be used appropriately. Two methods to monitor the
      performance of a classified environment where microbial recovery is zero are
      presented. Both methods use the frequency between non-zero microbial recovery as
      an event. Therefore, the frequency of events is monitored rather than the
      microbial recovery count. Both methods are shown to be appropriate for use in the
      described instances.

PMID- 15568647
TI  - A generalized plate method for estimating total aerobic microbial count.
AB  - The plate method outlined in Chapter 61: Microbial Limit Tests of the U.S.
      Pharmacopeia (USP 61) provides very specific guidance for assessing total aerobic
      bioburden in pharmaceutical articles. This methodology, while comprehensive,
      lacks the flexibility to be useful in all situations. By studying the plate
      method as a special case within a more general family of assays, the effects of
      each parameter in the guidance can be understood. Using a mathematical model to
      describe the plate counting procedure, a statistical framework for making more
      definitive statements about total aerobic bioburden is developed. Such a
      framework allows the laboratory scientist to adjust the USP 61 methods to satisfy
      specific practical constraints. In particular, it is shown that the plate method
      can be conducted, albeit with stricter acceptance criteria, using a test specimen
      quantity that is smaller than the 10 g or 10 mL prescribed in the guidance.
      Finally, the interpretation of results proffered by the guidance is re-examined
      within this statistical framework and shown to be overly aggressive.

PMID- 15568648
TI  - Evaluation of microparticles containing doxorubicin suitable for aerosol delivery
      to the lungs.
AB  - The efficacy of microparticulate systems containing anticancer agents may be
      assessed in vitro prior to evaluation of the effects of targeted and controlled
      drug release on tumor growth. Particles prepared in a size range suitable for
      aerosol delivery to the lungs (1-5 microm) would be useful in the treatment of
      locally occurring tumors. Bovine serum albumin microparticles containing
      doxorubicin (2.6-microm median diameter) were prepared by an emulsion technique
      with thermal stabilization. Dialysis was used to assess drug release in citrate
      phosphate buffer pH 4.0 and phosphate buffer pH 7.4, at 37 degrees C. Sixty
      percent of the doxorubicin load was released in a 10-h burst at pH 4.0. An
      additional 20% was released up to 70 h. Fifty percent of the drug was released in
      70 h at pH 7.4. S180 murine sarcoma cells were incubated with doxorubicin in
      solution and in microparticle suspension for 24, 48, and 72 h to evaluate
      cytotoxicity. Viable cells were recovered in smaller numbers following treatment
      with doxorubicin microparticles than following treatment with doxorubicin
      solution. The action of doxorubicin on growth of S180 murine sarcoma cells was
      enhanced in vitro by delivery in microparticles. A four-fold reduction in the
      effective dose, at which the rate of cell death exceeds replication, was observed
      for microparticles (5 microg/ml) than for doxorubicin alone (20 microg/ml).
      Therefore, the doxorubicin microparticles exhibit potential for greater
      therapeutic effect than drug alone when evaluated in vitro. Further studies are
      required to demonstrate the aerodynamic properties of these particles and
      efficacy in an in vivo tumor model.

PMID- 15568649
TI  - From novice to expert to mentor: shaping the future.

PMID- 15568650
TI  - Relational ethics of comfort, touch, and solace-endangered arts?

PMID- 15568651
TI  - Role of diastole in left ventricular function, II: diagnosis and treatment.
AB  - Left ventricular diastolic dysfunction plays an important role in congestive
      heart failure. Although once thought to be lower, the mortality of diastolic
      heart failure may be as high as that of systolic heart failure. Diastolic heart
      failure is a clinical syndrome characterized by signs and symptoms of heart
      failure with preserved ejection fraction (0.50) and abnormal diastolic function.
      One of the earliest indications of diastolic heart failure is exercise
      intolerance followed by fatigue and, possibly, chest pain. Other clinical signs
      may include distended neck veins, atrial arrhythmias, and the presence of third
      and fourth heart sounds. Diastolic dysfunction is difficult to differentiate from
      systolic dysfunction on the basis of history, physical examination, and
      electrocardiographic and chest radiographic findings. Therefore, objective
      diagnostic testing with cardiac catheterization, Doppler echocardiography, and
      possibly measurement of serum levels of B-type natriuretic peptide is often
      required. Three stages of diastolic dysfunction are recognized. Stage I is
      characterized by reduced left ventricular filling in early diastole with normal
      left ventricular and left atrial pressures and normal compliance. Stage II or
      pseudonormalization is characterized by a normal Doppler echocardiographic
      transmitral flow pattern because of an opposing increase in left atrial
      pressures. This normalization pattern is a concern because marked diastolic
      dysfunction can easily be missed. Stage III, the final, most severe stage, is
      characterized by severe restrictive diastolic filling with a marked decrease in
      left ventricular compliance. Pharmacological therapy is tailored to the cause and
      type of diastolic dysfunction.

PMID- 15568652
TI  - Equivalence of the bioimpedance and thermodilution methods in measuring cardiac
      output in hospitalized patients with advanced, decompensated chronic heart
      failure.
AB  - BACKGROUND: An accurate and reliable noninvasive method for determining cardiac
      output/cardiac index would be valuable for patients with acutely decompensated
      advanced systolic heart failure. OBJECTIVES: To determine whether a correlation
      exists for cardiac output and index determined by using bioimpedance and
      thermodilution in patients with acutely decompensated complex heart failure and
      if differences between results with the 2 methods could be explained by the
      patients' advanced condition. METHODS: Cardiac output and index were determined
      by using bioimpedance and thermodilution in 33 patients. Echocardiographic and
      electrocardiographic data were assessed to determine if differences between
      results with the 2 methods could be explained by the patients' advanced
      condition. Concordance correlation coefficients and Bland-Altman agreement
      between methods were calculated. RESULTS: Four patients were excluded from
      analysis because reliable measurements could not be obtained; the remaining 29
      patients constituted the study population. Mean cardiac outputs determined by
      thermodilution and bioimpedance were 5.48 and 5.40 L/min, respectively (rhoc =
      0.89, P < .001), and mean cardiac indexes were 2.67 and 2.65 (rhoc = 0.82, P <
      .001). Mean bias (limits of agreement) between data pairs was 0.08 (-0.18 to
      0.35) L/min (P = .52) for cardiac output and 0.03 (-0.097 to 0.16; P = .61) for
      cardiac index. Six data pairs (21%) had an absolute percent difference greater
      than 15%. Of these, 50% had a higher thermodilution value. CONCLUSION:
      Determinations of cardiac output and index by both methods were significantly
      correlated. Mean bias between the 2 methods was small, suggesting clinical
      utility for bioimpedance in patients with complex decompensated heart failure.

PMID- 15568653
TI  - Perceptions of physicians, nurses, and respiratory therapists about the role of
      acute care nurse practitioners.
AB  - BACKGROUND: Information about the contributions of acute care nurse practitioners
      to medical management teams in critical care settings is limited. OBJECTIVE: To
      examine contributions of acute care nurse practitioners to medical management of
      critically ill patients from the perspectives of 3 disciplines: medicine,
      respiratory care, and nursing. METHODS: Attending physicians, respiratory
      therapists, and nurses in 2 intensive care units were asked to list 3 advantages
      and 3 disadvantages of collaborative care provided by acute care nurse
      practitioners. Qualitative methods (coding/constant comparative analysis) were
      used to identify common themes and subthemes. Overall response rate was 35% (from
      69% for attending physicians to 26% for nurses). RESULTS: Responses were grouped
      into 4 main themes: accessibility, competence/knowledge, care
      coordination/communication, and system issues. Acute care nurse practitioners
      were valued for their accessibility, expertise in routine daily management of
      patients, and ability to meet patient/family needs, especially for "long-stay"
      patients. Also, they were respected for their commitment to providing quality
      care and for their communication skills, exemplified through teaching of nursing
      staff, patient/family involvement, and fluency in weaning protocols. Physicians
      valued acute care nurse practitioners' continuity of care, patient/family focus,
      and commitment. Nurses valued their accessibility, commitment, and patient/family
      focus. Respiratory therapists valued their accessibility, commitment, and
      consistency in implementing weaning protocols. CONCLUSION: Responses reflected
      unique advantages of acute care nurse practitioners as members of medical
      management teams in critical care settings. Despite perceptions of the acute care
      nurse practitioner's role as medically oriented, the themes reflect a clear
      nursing focus.

PMID- 15568654
TI  - Neonatal staff and advanced practice nurses' perceptions of bereavement/end-of
      life care of families of critically ill and/or dying infants.
AB  - BACKGROUND: Parents need compassionate care when an infant dies. Nurses can
      provide such care and possibly facilitate grieving, yet often have inadequate
      preparation in bereavement/end-of-life care. OBJECTIVE: To describe neonatal
      nurses' perceptions of bereavement/end-of-life care of families of critically ill
      and/or dying infants. METHODS: A cross-sectional, descriptive, correlational
      mailed survey design was used. The 55-item Bereavement End-of-Life Attitudes
      About Care: Neonatal Nurses Scale containing 4 sections (comfort, roles,
      involvement, and demographics) was mailed to 240 hospitals in the United States.
      RESULTS: The final response rate was 52% (190 completed data sets from 125
      hospitals). Respondents were comfortable with many aspects of bereavement/end-of
      life care. Comfort and roles scores correlated significantly with number of years
      as a neonatal intensive care nurse. Respondents agreed about many important
      aspects of their roles with patients' families, especially the importance of
      providing daily support to the families. Most respondents identified caring for a
      dying infant, the actual death of an infant, and language or cultural differences
      as influential factors in the level of their involvement with families.
      CONCLUSIONS: Education on bereavement/end-of-life care could affect nurses'
      comfort with caring for families of critically ill and/or dying infants.
      Additional education on cultural competence would be helpful. Educators must
      promote the inclusion of content on bereavement/end-of-life care in nursing
      curricula. Finally, researchers must focus more attention on factors that promote
      and inhibit bereavement/end-of-life care of families of critically ill and/or
      dying infants.

PMID- 15568655
TI  - Short-term complications and resource utilization in matched subjects after on
      pump or off-pump primary isolated coronary artery bypass.
AB  - BACKGROUND: Studies suggest that patients who undergo off-pump coronary artery
      bypass grafting (OPCABG) have fewer short-term complications and use fewer
      inpatient resources than do patients who undergo standard coronary artery bypass
      grafting (CABG) with extracorporeal circulation. However, dissimilarity between
      groups in risk factors for complications has hindered interpretation of results.
      OBJECTIVES: To compare the prevalence of selected complications (atrial
      fibrillation, stroke, reoperation, and bleeding) and inpatient resource
      utilization (length of stay, discharge disposition, total charges) between
      subjects undergoing primary isolated CABG or OPCABG who were matched with respect
      to key risk factors. METHODS: Retrospective, causal-comparative survey conducted
      in 1 center for 18 months. Patients who underwent primary isolated CABG or OPCABG
      were matched for sex, age (within 2 years), left ventricular ejection fraction
      (within 0.05), and graft-patient ratio (exact match) and compared for prevalence
      of new-onset atrial fibrillation, stroke, reoperation within 24 hours, and
      bleeding. Statistical analysis included Wilcoxon and t tests for paired
      comparisons. RESULTS: The sample (107 matched pairs) was 63% male, with a mean
      age of 66 (SD 9.5) years, a mean left ventricular ejection fraction of 0.51 (SD
      0.13), and a mean graft-patient ratio of 3.41 (SD 0.74). The 2 groups did not
      differ significantly in New York Heart Association class (P = .43), Acute
      Physiology and Chronic Health Evaluation III score (P = .22), postoperative beta
      blocker use (P = .73), or comorbid conditions. None of the complications examined
      differed significantly between pairs. CONCLUSION: Patients with comparable risk
      profiles have similar prevalences of selected complications after CABG and
      OPCABG.

PMID- 15568656
TI  - Listening to past leaders in medicine and nursing.

PMID- 15568657
TI  - Cardiac repair with autologous bone marrow stem cells.
AB  - All adults have stem cells in their body that can act like embryonic stem cells
      when given an appropriate stimulus. When VEGF is given, the bone marrow is
      stimulated to release stem cells, which grow new coronary arteries and also
      replenish damaged or dead cardiomyocytes. Transplanting autologous bone marrow
      stem cells into coronary arteries reduced infarct size, improved the prognosis
      following an acute MI and in patients with chronic congestive heart failure.
      Since patients are the source of their own stem cells, there would be a ready
      supply, with no rejection or immunological issues, and political debate on stem
      cell research would end. It is worth noting that statin therapy stimulates
      mobilization of EPCs, which repair damaged or dead myocardial cells and stimulate
      growth of new coronary arteries.

PMID- 15568658
TI  - Premature beats.

PMID- 15568659
TI  - [Lipid metabolism in diseases associated with the malabsorption syndrome].

PMID- 15568660
TI  - [Certain problems of the operated stomach associated with the Helicobacter pylori
      infection].

PMID- 15568661
TI  - [Effect of H2-blockers and proton pump inhibitors on intragastric acidity and
      intraesophageal pH in patients with gastroesophageal reflux disease].
AB  - We investigated 53 patients with GORD symptoms and a various grade (A-C according
      to the Los Angeles classification) of reflux oesophagitis diagnosed in the course
      of upper endoscopy. By using 24-hour gastric and esophageal pH-metry we
      investigated the antisecretory effect of single-dose morning or evening
      administration of famotidine, omeprazole and rabeprazole. We revealed essential
      superiority of single-dose morning omeprazole and rabeprazole administration in
      daily gastric acid release suppression and gastro-esophageal reflux prevention as
      compared with morning famotidine and evening omeprazole and rabeprazole
      administration in GORD patients.

PMID- 15568662
TI  - [Use of grandaxine in the treatment of patients with erosive-ulcerative stomach
      and gastroduodenal lesions].

PMID- 15568663
TI  - [Infection theory of the biliary pathology pathogenesis: is renaissance
      possible?].

PMID- 15568664
TI  - [State of humoral immunity and phagocytic activity of neutrophils in patients
      with ulcer and effect of low-intensity laser therapy].
AB  - The aim of our investigation was to study the influence of low-intensity laser
      therapy at the immunologic parameters and Helicobacter pylori (HP) microbial
      contamination in patients with exacerbation of peptic and duodenal ulcer. 100
      patients aged 18-65 were examined and divided into 2 groups. The experimental
      group (75 patients) underwent a complex drug and laser therapy of various
      therapeutic techniques. The control group (25 patients) underwent only drug
      therapy. The results of this study show the immunocorrective effect of different
      methods of low-intensity laser therapy in the exacerbation period and more
      essential decrease of HP microbial contamination in the experimental group.

PMID- 15568665
TI  - [Clinical and immunological aspects of low-intensity laser irradiation in
      patients with gastroduodenal ulcers].
AB  - Laser iridotherapy was carried out simultaneously with irradiation of immuno
      competent zones on the integument of the human body in patients with stomach and
      duodenal ulcers. As a result of such treatment, it was discovered that laser
      therapy has immunomodulating action leading to the reduction of the ulcer
      cicatrisation period.

PMID- 15568666
TI  - [Substantiation of enterosane application for the treatment of celiac disease].

PMID- 15568667
TI  - [Immunostimulating and anti-carcinogenic activity of the normal intestinal
      lactoflora].
AB  - One of major functions of lactic acid bacteria is their participation in the
      formation of local and systemic immune resistance of the host. The lactic acid
      bacteria associated with the mucous coat of the gastro-intestinal tract are
      cooperating with epitheliocytes, M-cells of Peyer's patches and various cells of
      the immune system. As a result of processing and presentation of specific cell
      components, lactic acid bacteria use mechanisms of modulation of cell-dependent
      immune response, activate RES and stimulate cytokine production. The article
      gives data on the role of lactic acid bacteria in the formation of T-and B-cell
      immune response, production of pro-inflammatory and anti-inflammatory cytokines
      ensuring the balance between humoral and cell-dependent immunity. The mechanisms
      of antitumor and oncostatic activity of lactic acid bacteria are analyzed. The
      polyfunctional influence of lactic acid bacteria on the immune reactions of the
      macroorganism includes the enhancement of the activity of monocyto-macrophages,
      natural killers and cytotoxic lymphocytes, modulation of reactions of the T- and
      B-cell immune responses, i.e. the complex system of interaction being formed
      between the indigenous intestinal microflora and the macroorganism is the basis
      of the normal function of its immune system.

PMID- 15568668
TI  - [Problems of excretory insufficiency of the pancreas].

PMID- 15568669
TI  - [Chronic constipations in elderly people].
AB  - Chronic constipations in elderly people proved to be an important medical and
      social problem due to their high prevalence and serious complications caused by
      the very disease and administration of stimulating laxatives. They include as
      follows: anorectic incontinence, large intestine obstruction, stercoral ulcers,
      laxative dependence and bowels toxic affection (Cathartic colon). Morphological
      and physiological prerequisites of chronic constipation and anorectic
      incontinence occurrence are examined in this review. Drugs and tactics for
      monitoring constipations depending on their severity, dominance of transit and
      evacuation disturbances, occurrence of anorectic incontinence are described.
      Characteristics of laxatives and intestinal motility regulators, range of side
      effects as well as experience of their application in elderly patients with
      functional constipations and irritable bowel syndrome are presented.

PMID- 15568670
TI  - [Clinical and pharmacoeconomic aspects of the antisecretory therapy of
      gastroesophageal refluxed disease].
AB  - The article discloses the results of an open prospective randomized study of the
      antisecretory therapy efficiency conducted among 20 patients with
      gastroesophageal refluxed disease (erosive form, non-complicated course). The
      selection of the optimal antisecretory drug was substantiated from the point of
      view of the clinic-diagnostic and pharmacoeconomic assessment of the results of
      the above-mentioned therapy conducted with the application of rabeprosole
      (pariet) and its generic omeprosole (omez).

PMID- 15568671
TI  - [Estimation of the hydrodynamical characteristics of the end-to-loop
      gastroenteroanastomosis].
AB  - The article presents the results of a study of the hydrodynamical characteristics
      of the end-to-loop gastroenteroanastomosis by the method of multichannel
      intraluminal manometry. The study was carried out on 7 outbreed dogs. The
      function of anastomosis was studied at the constant speed of liquid passage as
      well as at modeling short-term rises of pressure similar to those created by
      stomach and gut peristalsis. The results of the study testify that the end-to
      loop anastomosis is a dosed obstacle to the antegrade passage comparable with
      those in the normal state and has expressed antireflux properties.

PMID- 15568672
TI  - [Effect of the anesthesia method on the immune status of gerontological patients
      during abdominal operations].
AB  - As a rule, gerontological patients have a combination of senile physiological
      immunodeficiency and secondary immunodeficiency caused by various diseases. These
      states of the immune system are aggravated by stress immunodeficiency formed as a
      result of operative traumas and anesthesia. The immunodeficiency state (IDS) of
      such patients in many respects is determined by their interleukine status.
      Patients operated on abdominal cavity organs by the life-saving indication
      according to a delayed or scheduled procedure under conditions of epidural
      anesthesia (45 patients), spinal anesthesia (43 patients) and general anesthesia
      (41 patients) were examined. When generalizing the obtained results, it is
      necessary to mention that various types of anesthesia have a different effect on
      the immune and interleukine status of gerontological patients.

PMID- 15568673
TI  - [Restoration of nutritional status in patients with complicated course of ulcer
      during preoperative period].
AB  - The comparative analysis of the efficiency of the enteral tube feeding and
      parenteral feeding in 52 patients with the subcompensated stenosis of the pylorus
      was carried out. Satisfactory results were received in all groups of patients
      taking enteral and parenteral feeding. Consequently, the differences in the
      parameters of the catabolic index and general protein in the patients taking
      balanced food mixes rich in calories and 'usual feeding' were statistically
      significant. Complications caused by enteral tube feeding were observed in 23.3%.
      None of the patients having such complications required food suspension. The
      frequency and significance of such complications were higher (54.5%) in the group
      of the patients taking parenteral feeding. This study has shown that the enteral
      tube feeding is just as efficient as the parenteral feeding. Besides, the enteral
      tube feeding is characterized by less significant side effects and is more cost
      efficient.

PMID- 15568674
TI  - [Experimental assessment of the effect of dimephosphone on ulcerogenesis].

PMID- 15568675
TI  - [Protective effect of the intraperitoneal and intragastric administration of PGP
      peptide on ethanol-induced erosions and acetate-induced ulcers in rats].
AB  - We investigated the impact of PGP on ethanol-induced mucosal damages and on the
      development of acetate gastric ulcers in rats for two ways of introduction-
      intraperitoneal and intragastric. PGP in the dozes of 0.1, 1 and 10 mg/kg
      authentically reduced the area of ethanol-induced mucosal damages at
      intraperitoneal introduction by 43, 70 and 65%, respectively; at intragastric
      introduction--by 64, 66 and 83%, respectively. Intraperitoneal introduction of
      PGP in the doze of 1 mg/kg and its intragastric introduction in the doze of 0.1
      mg/kg equally reduced the development of acetate gastric ulcers by 73%. Thus,
      irrespective of the way of its introduction (intraperitoneal or intragastric) and
      its doze, PGP has a significant protective anti-ulcerous effect and reduces the
      development of acetate gastric ulcers in rats.

PMID- 15568676
TI  - [Arrangement of specialized public health care and the work experience of the
      gastroenterological center].
AB  - Arrangement of consulting gastroenterological centers at multi-type clinical
      hospitals makes it possible to render highly qualified medical care for adults,
      establish schools for training patients, render significant methodical assistance
      to medical staff on a permanent basis, especially during the period of the public
      health care system reorganization.

PMID- 15568677
TI  - [Comparative characteristics of treatment quality and quality of life in
      gastroenterological patients supervised by gastroenterologist and therapeutist].
AB  - There was an analysis of the results of a 5-year observation over 226 patients
      with the most prevailing digestive apparatus diseases: stomach ulcer and duodenal
      ulcer (SU and DU), chronic pancreatitis (CP), irritable bowel syndrome (IBS) in
      an outpatient clinic. Patients were supervised by gastroenterologists (168
      patients) and therapeutists (58 patients). It was noted that supervision of the
      patients by gastroenterologists authentically reduces the frequency of
      hospitalizations and duration of their stay on the sick-list as compared with the
      patients being observed by therapeutists and results in higher indices of life
      quality (LQ) among the patients.

PMID- 15568678
TI  - Search for substrate-based inhibitors fitting the S2' space of malarial aspartic
      protease plasmepsin II.
AB  - Plasmepsin (Plm) has been identified as an important target for the development
      of new antimalarial drugs, since its inhibition leads to the starvation of
      Plasmodium falciparum. A series of substrate-based dipeptide-type Plm II
      inhibitors containing the hydroxymethylcarbonyl isostere as a transition-state
      mimic were synthesized. The general design principle was provision of a
      conformationally restrained hydroxyl group (corresponding to the set residue at
      the P2' position in native substrates) and a bulky unit to fit the S2' pocket.

PMID- 15568679
TI  - Cyclic peptides selected by phage display mimic the natural epitope recognized by
      a monoclonal anti-colicin A antibody.
AB  - A 10-mer random peptide library displayed on filamentous bacteriophage was used
      to determine the molecular basis of the interaction between the monoclonal anti
      colicin A antibody 1C11 and its cognate epitope. Previous studies established
      that the putative epitope recognized by 1C11 antibody is composed of amino acid
      residues 19-25 (RGSGPEP) of colicin A. Using the phage display technique it was
      confirmed that the epitope of 1C11 antibody was indeed restricted to residues 19
      25 and the consensus motif RXXXPEP was identified. Shorter consensus sequences
      (RXXPEP, RXXEP, KXXEP) were also selected. It was also demonstrated that the
      disulfide bond found in one group of the selected peptides was crucial for 1C11
      antibody recognition. It was shown that cyclization of the peptides by disulfide
      bond formation could result in a structure that mimics the natural epitope of
      colicin A.

PMID- 15568680
TI  - Preparation of cyclic peptide libraries using intramolecular oxime formation.
AB  - A new method for the synthesis of cyclic head-to-side chain peptide libraries has
      been developed in which the key cyclization step involves reaction between a C
      terminal ketone and an N-terminal hydroxylamine to form a macrocyclic oxime. This
      methodology efficiently delivers cyclic products that consist of mixtures of syn
      and anti isomers.

PMID- 15568681
TI  - First chemical synthesis of a scorpion alpha-toxin affecting sodium channels: the
      Aah I toxin of Androctonus australis hector.
AB  - Aah I is a 63-residue alpha-toxin isolated from the venom of the Buthidae
      scorpion Androctonus australis hector, which is considered to be the most
      dangerous species. We report here the first chemical synthesis of Aah I by the
      solid-phase method, using a Fmoc strategy. The synthetic toxin I (sAah I) was
      renatured in DMSO-Tris buffer, purified and subjected to thorough analysis and
      comparison with the natural toxin. The sAah I showed physico-chemical (CD
      spectrum, molecular mass, HPLC elution), biochemical (amino-acid composition,
      sequence), immunochemical and pharmacological properties similar to those of the
      natural toxin. The synthetic toxin was recognized by a conformation-dependent
      monoclonal anti-Aah I antibody, with an IC50 value close to that for the natural
      toxin. Following intracerebroventricular injection, the synthetic and the natural
      toxins were similarly lethal to mice. In voltage-clamp experiments, Na(v) 1.2
      sodium channel inactivation was inhibited by the application of sAah I or of the
      natural toxin in a similar way. This work describes a simple protocol for the
      chemical synthesis of a scorpion alpha-toxin, making it possible to produce
      structural analogues in time.

PMID- 15568682
TI  - Solution conformational study of nociceptin an(d its 1-13 and 1-11 fragments
      using circular dichroism and two-dimensional NMR in conjunction with theoretical
      conformational analysis.
AB  - Conformational studies of nociceptin (NC-NH2), its fully active fragment, NC(1
      13)-NH2, and two significantly less potent fragments, NC(1-13)-OH and NC(1-11)
      OH, were conducted in water and TFE solutions by the employment of circular
      dichroism, and in DMSO-d6 by 2DNMR spectroscopy in conjunction with theoretical
      conformational analysis. The conformations of all thepeptides studied were
      calculated taking two approaches. The first assumes multiconformational
      equilibrium of the peptide studied, which is characterized by a set of
      conformations (and their statistical weight values)obtained from a global
      conformational analysis using three methods: the electrostatically driven Monte
      Carlo (EDMC) with the ECEPP/3 force field, the simulated annealing (SA) protocols
      in the AMBER and CHARMM force fields. The second approach incorporates the
      interproton distance and dihedral angle constraints into the starting
      conformation. Calculations were performed using the distance geometry and SA
      protocol in the CHARMM force field implemented in the X-PLOR program. The CD
      experiments indicated that for the active peptides, hydrophobic solvents induced
      a significantly higher (compared with those remaining)content order, probably a
      helical structure. Unfortunately, as a result of the conformational flexibility
      of thepeptides, the analysis of conformations obtained with both approaches and
      different force fields did not alllow the selection of any structural elements of
      the NC peptides that might be connected with their bioactivity. The only common
      element found in most conformations of the active peptides was a helical
      character of fragment 8-13, which allowed the side chains of basic amino acid
      residues to be exposed to the outside of the molecule and probably to interact
      with the ORL1 receptor.

PMID- 15568683
TI  - Novel features of amphiphilic peptide Mas7 in signalling via heterotrimeric G
      proteins.
AB  - Amphiphilic peptide Mas7, a structural analogue of mastoparan is a known
      activator of heterotrimeric Gi-proteins and its downstream effectors. This study
      investigated the functional interaction of Mas7 with a plasma membrane protein
      from CHO cells, the endogenous mono-ADP-ribosyltransferase. The substrate of
      endogenous mono-ADP-ribosyltransferase was the ADP-ribosylated protein with a
      molecular mass of 36 kDa, which corresponded to the beta subunit of
      heterotrimeric G-proteins. The effect of Mas7 on endogenous mono-ADP
      ribosyltransferase activity was in the micromolar range with a maximal activation
      of 205% over the basal. In pertussis treated plasma membranes, it was found that
      the effect of Mas7 on endogenous mono-ADP-ribosyltransferase was partially
      blocked, which suggests the involvement of G-proteins, such as Gi or G0. In
      addition, an immunoassay was developed for the visualization of interaction
      between the a subunit and the betagamma dimer of G-protein on a Ni-NTA support.
      The physical interaction was tested of Mas7 with the heterotrimeric G-protein
      alphai2 subunit, which was overexpressed together with beta1gamma2-His6 subunits
      in sf9 cells. An interaction between Gi2 heterotrimer and Mas7 was not observed,
      which was not in accordance with previously reported results of mastoparan
      obtained for Gi-proteins from bovine brain. In conclusion, the signal is mediated
      from Mas7 to endogenous mono-ADP-ribosyltransferase via pertussis sensitive G
      proteins. Furthermore, it is hypothesized that Gi2 G-proteins are not involved in
      the process.

PMID- 15568684
TI  - Understanding rib fracture patterns: incomplete and buckle fractures.
AB  - Reconstructing traumatic thoracic events, especially when soft tissues are
      absent, requires an advanced understanding of ribcage fracture patterns. The
      morphology and orientation of ribs complicate the fracture pattern, as a single
      blow often causes multiple fractures at various locations. Furthermore, fracture
      types observed in ribs are not explained easily by current bone biomechanic
      literature. Using evidential skeletal material archived at the Regional Forensic
      Center, Memphis, the ribs of 43 blunt force trauma cases were analyzed. A total
      of 195 incomplete fractures and 63 buckle fractures were noted. Incomplete
      fractures, previously thought to be common in children but rare in adults, were
      found among individuals ranging in age from 21-76 years. A buckle fracture,
      failure resulting from compressive instability, has been undefined previously in
      bone trauma literature but was repeatedly observed in this sample. This study
      elucidates recognizable rib fracture patterns while emphasizing gross bone
      examination for force and mechanical factors.

PMID- 15568685
TI  - A proposed method for the identification of race in sub-adult skeletons: a
      geometric morphometric analysis of mandibular morphology.
AB  - The identification of biological race (ancestry) in skeletal material is an
      important aspect of forensic investigations. While techniques for race
      determination are well established for adult skeletons, identification of race in
      sub-adult specimens has not been widely addressed. The present study investigates
      racial differences in the mandibular morphology of sub-adult specimens using
      geometric morphometric analyses. One hundred and seventy-four mandibles from five
      morphologically distinct samples were digitized and subjected to general
      Procrustes analysis. Results showed significant morphological differences between
      the samples and obtained cross-validation results of over 70% accuracy in
      identification of unknown individuals using the complete mandible. It is
      suggested that these techniques could provide a method for the identification of
      race in sub-adult individuals.

PMID- 15568686
TI  - Further evidence to show population specificity of discriminant function
      equations for sex determination using the talus of South African blacks.
AB  - Several studies have shown that osteometric differences exist between different
      population groups. Thus, discriminant function equations derived for the
      determination of sex from skeletal elements are population specific. In a
      previous study, the authors derived such equations from nine measurements of the
      talus of South African whites with high levels of average accuracies. The
      validity of some of the equations was tested on data collected from a South
      African black sample that consisted of 120 tali, equally distributed by sex,
      derived from the Raymond A. Dart Collection of Human Skeletons. The average
      accuracies dropped significantly. This necessitated the derivation of new
      equations for the South African black population and the average accuracies
      obtained ranged between 80% and 89%. The validity of the equations derived from
      the present study was tested using the leave-one-out classification and two
      independent samples (1 and 2). The applicability of the equations with very high
      classification rate from the present study was tested on Independent sample 1 of
      10 white tali with poor results. The result of the validity of these equations on
      an Independent sample 2 of 10 black tali revealed acceptably high average
      accuracies in correct classification thereby supporting earlier observations on
      population specificity of discriminant function equations.

PMID- 15568687
TI  - Highly sensitive screening method for nitroaromatic, nitramine and nitrate ester
      explosives by high performance liquid chromatography-atmospheric pressure
      ionization-mass spectrometry (HPLC-API-MS) in forensic applications.
AB  - A highly sensitive screening method based on high performance liquid
      chromatography atmospheric pressure ionization mass spectrometry (HPLC-API-MS)
      has been developed for the analysis of 21 nitroaromatic, nitramine and nitrate
      ester explosives, which include the explosives most commonly encountered in
      forensic science. Two atmospheric pressure ionization (API) methods, atmospheric
      pressure chemical ionization (APCI) and electrospray ionization (ESI), and
      various experimental conditions have been applied to allow for the detection of
      all 21 explosive compounds. The limit of detection (LOD) in the full-scan mode
      has been found to be 0.012-1.2 ng on column for the screening of most explosives
      investigated. For nitrobenzene, an LOD of 10 ng was found with the APCI method in
      the negative mode. Although the detection of nitrobenzene, 2-, 3-, and 4
      nitrotoluene is hindered by the difficult ionization of these compounds, we have
      found that by forming an adduct with glycine, LOD values in the range of 3-16 ng
      on column can be achieved. Compared with previous screening methods with
      thermospray ionization, the API method has distinct advantages, including
      simplicity and stability of the method applied, an extended screening range and a
      low detection limit for the explosives studied.

PMID- 15568688
TI  - Rapid screening of selected organic explosives by high performance liquid
      chromatography using reversed-phase monolithic columns.
AB  - This study presents the rapid screening of various high grade explosives by high
      performance liquid chromatography (HPLC) with monolithic stationary phases. Two
      gradient methods were developed, the first for quantitative analysis of eleven
      explosives: HMX; RDX; Tetryl; TNT; 2,3-DNT; 2,6-DNT; 3,4-DNT; 2-NT; 3-NT; 4-NT;
      and PETN in under 14 min. The second method separated seven explosives in under
      two min and is suitable for rapid screening to determine the presence of specific
      and/or class of explosive. The rapid screening methods were successfully applied
      to soils spiked with known amounts of target explosives. This technology showed
      excellent potential for forensic explosives detection and analysis.

PMID- 15568689
TI  - Characterization of allegedly musk-containing medicinal products in Taiwan.
AB  - As a highly valued ingredient of Chinese medicinal remedies, musk is used as a
      detoxification agent and for treating fever, inflammation and swelling, and pain.
      Muscone (3-methylcyclopentadecanone-1), an odoriferous secretion from the ventral
      glands of male musk deer, is believed to be the active ingredient. A small amount
      of muscopyridine is also found in the secretion from the ventral glands of male
      musk deer. Common counterfeit ingredients are musk xylene, musk ambrette, musk
      ketone, and diphenhydramine. An extraction/GC-MS protocol/data evaluation scheme
      was developed and applied to study allegedly musk-containing Musk-Tiger Bone
      Plaster preparations and musk pods (or grains) from Chinese medicine stores and
      an airport customs. The content of muscone in a specific sample was estimated
      based on the percentage of the amount recovered from the first extraction. No
      muscone or counterfeit ingredients were found in all musk pod (or grain) samples
      from the customs and in the majority of Musk-Tiger Bone Plaster preparations,
      while muscone (alone or with counterfeit ingredients) was found in most of the
      musk pod (or grain) collected from Chinese medicine stores.

PMID- 15568690
TI  - A novel method for extraction and analysis of gunpowder residues on double-side
      adhesive coated stubs.
AB  - A study was conducted to develop an efficient method for extraction and analysis
      of gunpowder (propellant) residues from double-side adhesive coated stubs, which
      are used for sampling suspects or their clothing for gunshot (primer) residues
      (GSR). Conductive and non-conductive double-side adhesives were examined, and the
      analysis was carried out by gas chromatography/thermal energy analyzer (GC/TEA)
      and ion mobility spectrometry (IMS). The optimal procedure for the extraction, as
      was developed in the present study, employs two stages: (1) extraction of the
      stubs with a mixture of 80% v/v aqueous solution of 0.1% w/v of sodium azide and
      20% v/v of ethanol employing sonication at 80 degrees C for 15 min. and (2)
      residues from the obtained extract were further extracted with methylene
      chloride. The methylene chloride phase was concentrated by evaporation prior to
      analysis. Extraction efficiencies of 30-90% for nitroglycerine (NG) and for 2,4
      dinitro toluene (2,4-DNT) were found. No significant interferences in the
      analysis were observed from the adhesives or skin. Interferences were observed in
      the analysis by the GC/TEA of the samples collected from hair. The method enables
      analysis of propellant residues on a double-side adhesive coated stub after it
      was examined for primer residues by scanning electron microscopy/energy
      dispersive X-ray spectroscopy (SEM/EDX). Thus, the probative value of the
      evidence may be increased.

PMID- 15568691
TI  - A genetic basis for anomalous band patterns encountered during DNA STR profiling.
AB  - Since 1995 the Forensic Science Service (FSS) has carried out DNA profiling of
      reference samples for the UK National DNA Database and in forensic casework using
      two multiplex STR profiling systems. During this period, profiles with anomalous
      banding patterns, although comparatively rare, have been encountered regularly.
      The FSS has collected instances of triallelic patterns and aberrant diallelic
      patterns. A systematic examination of these patterns has provided insight into
      their underlying genetic cause. The triallelic patterns could be classified into
      two types based on the relative intensities of their component alleles. In the
      Type 1 pattern the alleles were of uneven intensity, whereas in the Type 2
      pattern, all three alleles were of even intensity. Evidence is presented that the
      more frequent Type 1 pattern is the result of somatic mutation at a heterozygous
      locus, and the Type 2 pattern is the result of a localized chromosomal
      rearrangement at a heterozygous locus. Directly from the Type 1 pattern, it was
      possible to deduce the size difference between the progenitor and mutated allele.
      All mutational changes were found to be multiples of four nucleotides, suggesting
      the loss or addition of one or more tetrameric repeat units. Aberrant diallelic
      patterns were identified by analysts due to an unexpectedly large difference in
      intensity between alleles at a heterozygous locus. While some of these diallelic
      patterns are likely caused by the same genetic phenomena described above
      occurring at a homozygous locus, others are demonstrated to be caused by a
      mutation in the primer binding sequence, leading to a reduction in amplification
      efficiency of one allele. It is concluded that based on a visual inspection of a
      profile, it is possible to infer a likely genetic basis directly from the
      triallelic pattern. By contrast, the aberrant diallelic patterns can be due to
      any one of a number of possible genetic effects.

PMID- 15568692
TI  - Identification of firearms holders by the [Fe(PDT)3](+2) complex. Quantitative
      determination of iron transfer to the hand and its dependence on palmar moisture
      levels.
AB  - Quantitative data are reported for the first time on the amounts of iron, which
      are transferred to the hand upon holding a firearm. Iron levels between 21-315
      ng/cm2 were found on volunteers' palms after a single holding of a handgun.
      Determination of the iron traces was accomplished spectrophotometrically using 3
      (2-pyridyl)-5,6-diphenyl-1,2,4-triazine (PDT) as a complexing agent. The transfer
      of iron from firearms to the palm was found to be, by and large a chemical
      (dissolution) rather than mechanical dislodgement. The prime factor that
      determines the amount of iron transferred from the firearm to the hand is the
      moisture level on the palm. These findings are likely to be of importance in
      courts of law, as well as in the war against terrorism and serious crime.

PMID- 15568693
TI  - The reactivity of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL)
      in alcoholic solutions.
AB  - In this work the stability of GBL (gamma-butyrolactone) and GHB (gamma
      hydroxybutyric acid) in alcoholic media was studied. Under acidic conditions the
      GBL will react with ethanol or methanol to give the corresponding ethyl and
      methyl esters of GHB. It can be seen that ester formation is dependent on the
      type of alcohol, the alcohol content of the solution, and the pH of the solution.
      Under the same conditions it was shown that GHB does not give rise directly to
      the corresponding ester when merely in the presence of an alcohol; however the
      ester will be formed if the conditions are present for conversion of GHB to GBL
      followed by subsequent reaction with alcohol. In alcoholic beverage samples
      spiked with GBL the expected conversion to GHB occurred, and the formation of the
      ethyl ester of GHB was also seen in some samples. Wine samples were analyzed for
      the presence of the ethyl ester of GHB, and the effect of adding GHB/GBL to hot
      beverages was studied.

PMID- 15568694
TI  - Trace analysis of peroxide explosives by high performance liquid chromatography
      atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC-APCI
      MS/MS) for forensic applications.
AB  - An HPLC-APCI-MS(/MS) method for the (trace) analysis of the most commonly
      encountered peroxide explosives, hexamethylenetriperoxidediamine (HMTD) and
      triacetonetriperoxide (TATP), has been developed. With this method, HMTD and TATP
      have been analyzed in the same run. (Pseudo-)molecular ions of these peroxides
      have been obtained as base peak under the same condition. A series of product
      ions was produced from these pseudo-molecular ions ([HMTD - 1]+ and [TATP +
      NH4]+) in the MS/MS analysis. We also pioneered in showing that a TATP molecular
      ion [TATP + H]+ can be observed with HPLC-MS/MS. The limit of detection for HMTD
      and TATP was 0.26 and 3.3 ng, respectively, on column by HPLC-MS in the Full Scan
      mode and 0.08 and 0.8, respectively, by HPLC-APCI-MS/MS in Selected Reaction
      Monitoring (single mass unit) mode. The method presented has been applied
      successfully for the identification of peroxides in the bulk solid state (powder
      sample), as well as in post-blast extracts originating from a forensic case. For
      the post-blast extracts, the use of tandem MS has been shown clearly to be of
      crucial importance for the identification and detection of the peroxide
      explosives.

PMID- 15568695
TI  - Gunshot residue particle velocity and deceleration.
AB  - The velocity of over 800 gunshot residue particles from eight different sources
      was determined using high speed stroboscopic photography (spark gap light
      source). These particles were found to have an average velocity of 500 to 600 ft
      per second. Many particles acquired considerably higher velocities. Thus, the
      particles have sufficient energy to embed themselves within certain nearby
      targets like skin or fabric. The relatively high velocity that the particles
      acquire explain the formation of stippling on skin in close proximity to a muzzle
      discharge. These findings also indicate little influence of air currents on
      particle behavior near the muzzle. The deceleration of less than 100 particles
      during a 100-microsecond interval was also calculated. The particles experienced
      rapid rates of deceleration which would explain why few particles are found in
      test firings beyond 3 ft from the muzzle of a discharged firearm. Because of
      their relatively high velocity, normal wind velocity would not be expected to
      significantly influence their motion near the muzzle.

PMID- 15568696
TI  - The evidential value of cosmetic foundation smears in forensic casework.
AB  - Cosmetic foundation products are easily transferred to clothing and other
      surfaces as a result of contact with such objects. Examination of past cases
      involving cosmetics in New Zealand has shown cosmetic foundation to be one of the
      more common cosmetic products encountered. The aim of this research was to
      determine the most discriminating method for the comparison of transferred
      foundation with samples obtained from a known source in forensic casework. Fifty
      three foundation samples were analyzed by Fourier transform infrared spectroscopy
      (FTIR), gas chromatography with a flame ionization detector (GC-FID) and scanning
      electron microscopy-energy dispersive X-Ray analysis (SEM-EDX). It was found that
      a 5 mm2 section of a light smearing was enough to provide detectable results. The
      discriminating powers for FTIR, SEM-EDX and GC-FID were 98.3, 93.8, and 82.0%
      respectively. A combination of all three techniques provided a discriminating
      power of 99.7%, meaning that almost complete discrimination was achieved between
      the foundation samples.

PMID- 15568697
TI  - A comparison study of hair examination methodologies.
AB  - A study was conducted to investigate the accuracy between two methods of hair
      analysis: PCR-STR DNA analysis and microscopic comparison analysis. Standard sets
      of pubic hairs were collected from volunteers, and unknown sets were generated
      from these samples. Three out of five (60%) of the hairs analyzed produced full
      DNA profiles that were correctly matched to the standard sets. DNA analysis was
      inconclusive (partial or no DNA profile) for two out of five (40%) of the
      samples. In contrast, the microscopic comparison analysis correctly matched four
      out of five (80%) of the samples to the standard sets but mis-identified one out
      of five (20%) of the samples. These results reinforce the practice of preliminary
      microscopic hair examination in narrowing down a set of hairs for DNA analysis.
      Microscopic comparison analysis is sufficiently reliable to remain a rapid and
      inexpensive method for forensic hair analysis.

PMID- 15568698
TI  - Addressing the use of phylogenetics for identification of sequences in error in
      the SWGDAM mitochondrial DNA database.
AB  - The SWGDAM mtDNA database is a publicly available reference source that is used
      for estimating the rarity of an evidence mtDNA profile. Because of the current
      processes for generating population data, it is unlikely that population
      databases are error free. The majority of the errors are due to human error and
      are transcriptional in nature. Phylogenetic analysis of data sets can identify
      some potential errors, and coupled with a review of the sequence data or
      alignment sheets can be a very useful tool. Seven sequences with errors have been
      identified by phylogenetic analysis. In addition, two samples were inadvertently
      modified when placed in the SWGDAM database. The corrected sequences are provided
      so that users can modify appropriately the current iteration of the SWGDAM
      database. From a practical perspective, upper bound estimates of the percentage
      of matching profiles obtained from a database search containing an incorrect
      sequence and those of a database containing the corrected sequence are not
      substantially different. Community wide access and review has enabled
      identification of errors in the SWGDAM data set and will continue to do so. The
      result of public accessibility is that the quality of the SWGDAM forensic dataset
      is always improving.

PMID- 15568699
TI  - Specificity of sibship determination using the ABI Identifiler multiplex system.
AB  - Fifty known siblings and fifty unrelated pairs were genotyped using the ABI
      Identifiler STR system and sibship indices computed for each pair. Combined
      sibship indices (CSIs) for the known siblings ranged from less than 10 to greater
      than 1 billion. CSIs for the unrelated pairs ranged from 4.5 x 10(-8) to 0.12. In
      the known sibling group the percentage of loci where both alleles matched was
      approximately 40%, while the percentage of loci where neither matched was
      approximately 10%. In the non-sibling group, the percentage of loci where both
      alleles matched was approximately 6%, while the percentage of loci where neither
      matched was approximately 45%. Interestingly, the percentage of loci where a
      single allele matched was the same in both the known siblings and unrelated
      pairs, approximately 50%.

PMID- 15568700
TI  - Developmental validation of a single-tube amplification of the 13 CODIS STR loci,
      D2S1338, D19S433, and amelogenin: the AmpFlSTR Identifiler PCR Amplification Kit.
AB  - Analysis of length polymorphism at short tandem repeat (STR) loci utilizing the
      polymerase chain reaction (PCR) process has proven to be an ideal assay for human
      identification purposes. The short length of STR loci coupled with the
      amplification of target sequence through PCR allows for a robust, sensitive, and
      specific assay for highly polymorphic markers. A multiplex containing fifteen STR
      loci plus the gender-determining locus Amelogenin was developed to provide a
      single amplification/detection of all CODIS (Combined DNA Index System) STR loci
      (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA,
      TH01, TPOX, and vWA) as well as two internationally-accepted STRs (D2S1338 and
      D19S433). By incorporating five-dye fragment analysis technology and non
      nucleotide linkers, previously optimized AmpFlSTR kit primer sequences have been
      maintained. This kit has been developed in accordance with the standards of the
      forensic community as defined by the DNA Advisory Board. Validation studies were
      performed to include developmental validation, and the results support the use of
      the AmpFlSTR Identifiler PCR Amplification Kit for human identity and parentage
      testing.

PMID- 15568701
TI  - Y-chromosome STR system, Y-PLEX 12, for forensic casework: development and
      validation.
AB  - The Y-PLEX 12 system, developed for use in human identification, enables
      simultaneous amplification of eleven polymorphic short tandem repeat (STR) loci,
      namely DYS392, DYS390, DYS385 a/b, DYS393, DYS389I, DYS391, DYS389II, DYS 19,
      DYS439 and DYS438, residing on the Y chromosome and Amelogenin. Amelogenin
      provides results for gender identification and serves as internal control for
      PCR. The validation studies were performed according to the DNA Advisory Board's
      (DAB) Quality Assurance Standards. The minimal sensitivity of the Y-PLEX 12
      system was 0.1 ng of male DNA. The mean stutter values ranged between 3.76
      15.72%. A full male profile was observed in mixture samples containing 0.5 ng of
      male DNA and up to 400 ng of female DNA. Amelogenin did not adversely affect the
      amplification of Y-STRs in mixture samples containing male and female DNA. The
      primers for the Y-STR loci present in Y-PLEX 12 are specific for human DNA and
      some higher primates. None of the primate samples tested provided a complete
      profile at all 11 Y-STR loci amplified with the Y-PLEX 12 system. Y-PLEX 12 is a
      sensitive, valid, reliable, and robust multiplex system for forensic analysis,
      and it can be used in human forensic and male lineage identification cases.

PMID- 15568702
TI  - Defining event reconstruction of digital crime scenes.
AB  - Event reconstruction plays a critical role in solving physical crimes by
      explaining why a piece of physical evidence has certain characteristics. With
      digital crimes, the current focus has been on the recognition and identification
      of digital evidence using an object's characteristics, but not on the
      identification of the events that caused the characteristics. This paper examines
      digital event reconstruction and proposes a process model and procedure that can
      be used for a digital crime scene. The model has been designed so that it can
      apply to physical crime scenes, can support the unique aspects of a digital crime
      scene, and can be implemented in software to automate part of the process. We
      also examine the differences between physical event reconstruction and digital
      event reconstruction.

PMID- 15568703
TI  - A mobile system for postmortem genital examinations with colposcopy: SART-TO-GO.
AB  - The interpretation of genital findings in the deceased is a vital and timely
      issue. A paucity of information exists on the nature and appearance of the
      anogenital tissues in the postmortem interval. The traditional postmortem genital
      examination consists of gross visualization, which may preclude detection of the
      subtler trauma that usually constitutes injury in sexual assault. The mobile
      system grew out of a need to bring the examiner to the patient, e.g., in
      jurisdictions that lack a centralized morgue. The theoretical framework of the
      methodology lies in the sexual activity that culminates in the death of the
      sexual homicide victim. This sequential methodology was based on the Sexual
      Assault Response Team (SART) model, with adaptation to the autopsy milieu.
      Colposcopy is well-established for the medical-legal investigation of living
      sexual assault victims. During the author's initial rape-homicide examinations,
      only gross visualization was available. It soon became apparent that a system
      that facilitated detailed scrutiny of the anogenital tissues at various
      postmortem intervals was needed. Colposcopy was selected as the examination
      method because of its magnification, photodocumentation, and peer review
      potential. The sequential protocol was developed and refined during an ongoing
      accumulation of baseline cases. The role of the forensic nurse examiner is
      described within a defined scope of expertise and as a collaborative member of
      the homicide investigative team.

PMID- 15568704
TI  - The rarity of "unusual" [corrected] dispositions of victim bodies: staging and
      posing.
AB  - The act of leaving a victim's body in an unusual position is a conscious criminal
      action by an offender to thwart an investigation, shock the finder and
      investigators of the crime scene, or give perverted pleasure to the killer. The
      unusual position concepts of posing and staging a murder victim have been
      documented thoroughly and have been accepted by the courts as a definable
      phenomenon. One staging case and one posing case are outlined and reveal
      characteristics of those homicides. From the Washington State Attorney General's
      Homicide Investigation and Tracking System's database on murder covering the
      years 1981-2000 (a total of 5,224 cases), the relative frequency of unusual body
      dispositions is revealed as a very rare occurrence. Only 1.3% of victims are left
      in an unusual position, with 0.3% being posed and 0.1% being staged. The
      characteristics of these types of murders also set them apart: compared to all
      other murders, in staged murders the victims and killers are, on average, older.
      All victims and offenders in the staged murders are white, with victims being
      disproportionately white in murders with any kind of unusual body disposition.
      Likewise, females stand out as victims when the body is posed, staged, or left in
      other unusual positions. Whereas posed bodies are more likely to include sexual
      assault, often in serial murders, there is no evidence of either in the staged
      cases. Lastly, when a body is left in an unusual position, binding is more
      likely, as well as the use of more "hands on" means of killing the victim, such
      as stabbing or cutting weapons, bludgeons, ligatures, or hands and feet.

PMID- 15568705
TI  - Factors affecting postmortem tooth loss.
AB  - Unassociated human bones are a particular problem during the exhumation of mass
      graves and a factor that limits anthropological and paleopathological analyses
      from archaeological contexts. Extensive anthropological literature has focused on
      the complex taphonomic factors that influences bone assemblages, but little
      attention has been paid to postmortem tooth loss and factors affecting this
      process. The following study focuses upon the influence of different factors on
      postmortem tooth loss. Three samples were investigated in the study: a medieval
      church cemetery containing 110 individual skeletal remains, and two samples from
      a series of mass graves made within the same time period in 1999, containing 402
      bodies. The frequency of postmortem tooth loss was analyzed relative to
      postmortem interval for each sample, excavation methods, age distribution, and
      presence of bone loss associated with periodontal disease. Our results indicate
      that the degree of alveolar bone loss significantly affected both antemortem and
      postmortem tooth loss and that the frequency of postmortem tooth loss has the
      strongest correlation to time since death. These findings suggest that additional
      care should be taken when exhuming remains from older contexts.

PMID- 15568706
TI  - Precision and reliability of pulp/tooth area ratio (RA) of second molar as
      indicator of adult age.
AB  - This paper discusses a method for assessing adult age based on the relationship
      between age and measurement of the pulp/tooth area ratio (RA) of the second molar
      teeth. The sample consisted of 312 Italian white Caucasian patients (135 men, 177
      women) aged between 14 and 24 years. Orthopantomograph samples (OPGs) were
      analyzed by the same observer and calibrated by kappa statistics. Probabilities
      of an individual being older than 18 years of age (adult age) were derived using
      measurements of the ratio pulp/tooth area (RA) of the second molar teeth and the
      dichotomized stages of third molar development (Tm) as explanatory variables.
      These results were exploited to establish a threshold value to assign an
      individual to juvenile or adult age. A cut-off value of RA* = 0.088 was applied
      if Tm = 0 and RA* = 0.097 if Tm = 1. The sensitivity of this test was 91% and its
      specificity 94.5%. The proportion of individuals with correct classifications was
      92%.

PMID- 15568707
TI  - Dental maturity curves in Finnish children: Demirjian's method revisited and
      polynomial functions for age estimation.
AB  - Dental maturity was studied from 2213 dental panoramic radiographs of healthy
      ethnic Finns from southern Finland, aged between 2 and 19 years. The aim was to
      provide new Finnish maturity tables and curves and to compare the efficiency of
      Demirjian's method when differently weighted scores and polynomial regressions
      are used. The inter-ethnic variations lead us to calculate specific Finnish
      weighted scores. Demirjian's method gives maturity score as a function of age and
      seems better adapted for clinicians because, in their case, the maturity score is
      unknown. Polynomial functions give age as a function of maturity score and are
      statically adapted for age estimation studies. Finnish dental maturity tables and
      development curves are given for Demirjian's method and for polynomial functions.
      Sexual dimorphism is established for the same weighted score for girls and boys,
      and girls present a greater maturity than boys for all of age groups. Polynomial
      functions are highly reliable (0.19% of misclassifies) and the percentile method,
      using Finnish weighted scores, is very accurate (+/- 1.95 years on average,
      between 2 and 18 years of age). This suggests that polynomial functions are most
      useful in forensic sciences, while Demirjian's method is most useful for dental
      health clinicians.

PMID- 15568708
TI  - Old dogs can learn new tricks--a new application of the ABFO #2 scale.
AB  - In 1984 at its first Bitemark Workshop, the American Board of Forensic Odontology
      (ABFO) developed guidelines for the analysis of bitemark evidence. Prior to this,
      no standards had been established for the evaluation of bitemarks. The
      development of the ABFO #2 scale in 1987 gave the forensic odontologist a
      reproducible way to rectify and measure bitemarks that had been documented
      photographically. Primarily developed for the analysis of bitemark evidence, its
      use has expanded to encompass myriad forms of evidence. While the ABFO #2 scale
      can depict horizontal and vertical measurements, it is unable to depict depth
      accurately. The purpose of this paper is to show its successful application to
      three dimensions.

PMID- 15568709
TI  - Common mitochondrial DNA deletion associated with sudden natural death in adults.
AB  - One of the most frequent causes of death in developed countries is sudden natural
      death (SND), which is the most common indication for medico-legal autopsies.
      Cardiac diseases are frequently detected among SND. Mitochondrial DNA (mtDNA) is
      easily damaged by reactive oxygen species, and it may cause dysfunction in
      tissues, leading to early events in cardiovascular disease. A specific mtDNA
      deletion of 4977 bp is associated to aging, myocardial dysfunction, and
      bioenergetic deficit. The potential link between mtDNA damage and SND has not
      been investigated before. Our aim was to evaluate the accumulation of the common
      mtDNA4977-deletion in cardiac muscle samples from autopsies of SND in adults (n =
      14) in comparison to control samples from unnatural deaths (n = 12). Serial
      dilution-polymerase chain reaction method was performed to estimate the
      proportion of the total mtDNA harboring the mtDNA4977-deletion. Coefficient
      variation intra-assay was 8%, and inter-assay was 12%. MtDNA4977-deletion
      percentage was higher in samples obtained from victims of SND than in those from
      subjects who died of unnatural causes (p < 0.05). No differences in mtDNA4977
      deletion were found between SND victims 39-51 years old, and no correlation was
      found between these samples and age, r = 0.30, p = 0.29 while it was significant
      among control samples, r = 0.68, p < 0.05. The association between mtDNA4977
      deletion with SND victims might offer a tool to provide additional information to
      clarify complex SND investigations.

PMID- 15568710
TI  - Visualization and quantification of air embolism structure by processing
      postmortem MSCT data.
AB  - Venous air embolism (VAE) is an often occurring forensic finding in cases of
      injury to the head and neck. Whenever found, it has to be appraised in its
      relation to the cause of death. While visualization and quantification is
      difficult at traditional autopsy, Magnetic Resonance Imaging (MRI) and Computed
      Tomography (CT) offer a new potential in the diagnosis of VAE. This paper reports
      the findings of VAE in four cases of massive head injury examined postmortem by
      Multislice Computed Tomography (MSCT) prior to autopsy. MSCT data of the thorax
      were processed using 3D air structure reconstruction software to visualize air
      embolism within the vascular system. Quantification of VAE was done by
      multiplying air containing areas on axial 2D images by their reconstruction
      intervals and then by summarizing the air volumes. Excellent 3D visualization of
      the air within the vascular system was obtained in all cases, and the
      intravascular gas volume was quantified.

PMID- 15568711
TI  - Treatment of paraphilia in young adults with leuprolide acetate: a preliminary
      case report series.
AB  - Some juveniles who engage in sexual offenses may have a paraphilia, a psychiatric
      disorder characterized by a pervasive pattern of deviant and impairing sexual
      fantasies, thoughts, and/or behaviors. Though there is no known cure for these
      conditions, paraphilias can be effectively managed using a multimodal treatment
      approach. This may include the use of psychotherapeutic and pharmacological
      treatment interventions, including antiandrogen medications. One such agent,
      leuprolide acetate (leuprolide), a luteinizing hormone-releasing-hormone agonist,
      has been shown to be effective in reducing paraphilic symptoms in adult patients.
      To date, however, there is no published data on its use and effectiveness in
      adolescent and young adult paraphilic patients. This study consists of a case
      report series of six young adult patients treated with leuprolide. All subjects
      had been diagnosed with at least one paraphilia (i.e., Pedophilia, Sexual Sadism,
      Frotteurism, and Paraphilia Not Otherwise Specified). All subjects had been
      refractory to treatment in a residential program for adolescent sex offenders
      prior to initiation of leuprolide. All six subjects reported a reduction in
      sexually deviant symptoms following treatment with leuprolide. Clinicians rated
      four as much improved and two as moderately improved. The treatment was well
      tolerated in all six subjects. This preliminary case series supports the
      conclusion that leuprolide deserves further examination as a potentially safe and
      effective component in the treatment of young adult patients with paraphilia.

PMID- 15568712
TI  - Comparison of near infrared light photography and middle infrared light
      photography for deciphering obliterated writings.
AB  - There are obliterated writings that are undecipherable by conventional visible
      and near infrared monochromatic light photography. Some of them could be
      deciphered undestructively by middle infrared light photography. Characters were
      written on paper with 101 kinds of pens. Middle infrared light photographs and
      near infrared light photographs of them were taken and compared to recognize what
      kinds of inks is transparent at examined wavelength regions. Based on the results
      obtained, the combination of ink for drawing and obliterating (which is not
      deciphered by visible and near infrared light photography, but expected to be
      deciphered with middle infrared light photography) is selected. From the examined
      photographs, it is demonstrated that there exist obliterated writings which are
      undecipherable by conventional near infrared light photography, but decipherable
      by middle infrared light photography.

PMID- 15568713
TI  - Dating of ballpoint pen ink.
AB  - In this paper we describe a case in which a cash book, dated of the year 2000,
      was sent to the Forensic Science Division, Document Laboratory, Zurich Canton
      Police in March 2003. The questioned document was a list of 29 pages containing a
      consecutive handwritten numbering and dated entries (payments) made of blue
      ballpoint pen ink. By definition, a cash book has to be written by hand and the
      entries have to be made daily. The questioned document was suspected to have been
      written within a short period (e.g., a few hours) and backdated. The document lab
      was asked to determine the date of the entries of the questioned list. On one
      hand, we were asked, if the cash book had been kept on account consecutively
      during the period of one year, and on the other hand, the judges were interested
      in knowing, if the document could have been written in 2003 and back dated to
      2000. To answer these questions, the document was examined for latent elements by
      electrostatic detection device (ESDA). The relative dating of the entries was
      performed by the quantification of the ballpoint pen ink dyes and their
      degradation products using HPLC. Results show that it is possible to determine
      the relative age of entries written by ballpoint pen within a relatively short
      time scale, if storage and supporting material of the different samples are the
      same or at least similar.

PMID- 15568714
TI  - Oxycodone intoxication in an infant: accidental or intentional exposure?
AB  - A case is presented of a 10 month old male who went into cardiac arrest at a
      local store. The infant subsequently expired and was autopsied at the Office of
      the Chief Medical Examiner, State of Maryland. The only remarkable finding was
      the detection of oxycodone in the postmortem specimens; the blood and liver
      oxycodone concentrations were 0.6 mg/L and 1.6 mg/kg, respectively. Oxycodone was
      identified and quantitated by gas chromatography-nitrogen-phosphorus detection
      and confirmed by full scan electron ionization gas chromatography-mass
      spectrometry. The medical examiner ruled that the cause of death was oxycodone
      intoxication, and the manner of death was homicide. The key toxicologic question
      in this case was whether or not it was reasonable for the infant to be exposed to
      oxycodone exclusively through breast milk or through an alternate source. It was
      concluded that, at best, there were serious concerns about the likelihood of drug
      exposure through consumption of breast milk.

PMID- 15568715
TI  - Fatality due to methyl acetylene-propadiene (MAPP) inhalation.
AB  - A 33-year-old man died after intentionally inhaling a gaseous mix of methyl
      acetylene (propyne) and propadiene (allene) commonly known as MAPP, which is used
      for soldering and welding. He was found with a plastic bag securely placed over
      his head and a cylinder of MAPP alongside his head. The cylinder had been vented
      into the bag using a flexible hose. A comprehensive toxicological analysis
      revealed only a trace of diphenhydramine in the liver and 0.02 mg/L of morphine
      in the urine. Analysis of blood by headspace gas chromatography (HS-GC) detected
      two unknown peaks. These were determined to be the components of MAPP gas. MAPP
      was quantitated in femoral blood (59.6 mg/L) and brain (43.6 mg/kg) using a HS-GC
      method. The cause of death was attributed to acute MAPP intoxication, and the
      manner was determined to be suicide. A discussion on the analytical and
      interpretive considerations commonly encountered when analyzing volatile
      compounds is also presented.

PMID- 15568716
TI  - Deaths after intravenous misuse of transdermal fentanyl.
AB  - Fentanyl is a potent synthetic opioid used as a general anesthetic and analgetic.
      Fatal outcome from intravenous misuse of transdermal fentanyl is rare, and there
      are few such reports in literature. Here we report two cases of fatal intravenous
      injection of the content from fentanyl patches. Both were male drug addicts,
      found dead within a one week interval in the same apartment. Post-mortem femoral
      blood was screened for amphetamines, cannabinoids, cocaine, and opioids with
      immunological methods (EMIT II) and further with headspace gas chromatography for
      alcohol and with liquid chromatography mass spectrometry (LC-MS) for different
      drugs, including fentanyl. Confirmatory analysis of fentanyl and morphine was
      performed by gas chromatography-mass spectrometry (GC-MS). In the first case, the
      toxicological analysis revealed fentanyl (2.7 ng/mL), morphine (31.4 ng/mL), and
      ethanol (1.1 g/L) in postmortem blood and amphetamine, cannabinoids, morphine,
      and ethanol (1.4 g/L) in postmortem urine. In the second case, the analysis
      revealed fentanyl (13.8 ng/mL), 7-aminoclonazepam (57.1 ng/mL), and sertralin
      (91.9 ng/mL) in postmortem blood and a small amount of ethanol (0.1 g/L) in
      postmortem urine. Police investigation revealed that both the deceased had bought
      the patches from the same source. The present cases demonstrate the possibility
      of intravenous misuse of transdermal patches and the risk of fatal outcome.

PMID- 15568717
TI  - Distributions of allelic frequencies of three new STR loci in a Chinese Han
      population.

PMID- 15568718
TI  - Population data on 9 STR loci in Crete (Greece).

PMID- 15568719
TI  - Population genetics for three STR loci in the population from southern China.

PMID- 15568720
TI  - Allele frequency distribution of STR loci D5S2848 in four populations.

PMID- 15568721
TI  - Polymorphism data of two STR loci DYS632 and DYS634 in a Chinese Han population.

PMID- 15568722
TI  - Distribution of HLA-DQA1, LDLR, GYPA, HBGG, D7S8 and Gc alleles in a Black
      population sample from Sao Paulo, Brazil.

PMID- 15568723
TI  - Population genetic data at two minisatellites (D19S20 and APOB 3' VNTR) between
      two tribal populations from Central India.

PMID- 15568724
TI  - Distribution of allele frequencies of a STR (D5S580) marker in five population
      groups of Kerala in south India.

PMID- 15568725
TI  - Genetic data of two STR loci D4S2367, D20S601 in Chinese population.

PMID- 15568726
TI  - Genetic analysis of large data sets of North American Black, Caucasian, and
      Hispanic populations at 13 CODIS STR loci.

PMID- 15568727
TI  - Genetic polymorphism for two STR loci D4S2639 and D4S1644 in a Chinese
      population.

PMID- 15568728
TI  - Successful identification of two years old menstrual bloodstain by using MMP-11
      shorter amplicons.

PMID- 15568729
TI  - Commentary on: Budowle B, Shea B, Niezgoda S, Chakraborty r. CODIS STR loci data
      from 41 sample populations. J Forensic Sci 2001;46:453-489.

PMID- 15568730
TI  - Triplex forming oligonucleotides--tool for gene targeting.
AB  - This review deals with the antigene strategy whereby an oligonucleotide binds to
      the major or minor groove of double helical DNA where it forms a local triple
      helix. Preoccupation of this article is triplex-forming oligonucleotides (TFO).
      These are short, synthetic single-stranded DNAs that recognize
      polypurine:polypyrimidine regions in double stranded DNA in a sequence-specific
      manner and form triplex. Therefore, the mechanisms for DNA recognition by triple
      helix formation are discussed, together with main characteristics of TFO and also
      major obstacles that remain to be overcome are highlighted. TFOs can selectively
      inhibit gene expression at the transcriptional level or repair genetic defect by
      direct genome modification in human cells. These qualities makes TFO potentially
      powerful therapeutic tool for gene repair and/or expression regulation.

PMID- 15568731
TI  - Endothelins and sarafotoxins: peptides of similar structure and different
      function.
AB  - Endothelins are endogenous vasoactive peptides that are considered among the most
      potent vasoconstrictor substances known. In addition to their vascular effects,
      endothelins and their receptors have been shown to be present in many organs and
      share plenty physiological and pathophysiological functions. Sarafotoxins are
      natural substances from the venom of snakes genus Atractaspis, structurally and
      pharmacologically near to endothelins. The current minireview focuses on the
      chemical and molecular aspects of endothelins and sarafotoxins, and their
      receptors in physiological and pathophysiological processes.

PMID- 15568732
TI  - Stimulation of ileal epithelium growth and regeneration by dietary nucleotide
      extracts.
AB  - The gastrointestinal tract epithelium plays an important role not only in
      digestion and absorption of nutrients, but also in antigen and pathogen signal
      translocation toward the gut associated lymphoid tissue. Malnutrition in various
      degrees is recognized as the most common cause of the immune system dysfunction.
      Research done in the past several years has revealed that dietary nucleotides
      (dNT) represent an essential compound of nutrition because of their importance in
      metabolic pathways, energetic processes and nucleic acid synthesis during tissue
      renewal. Much evidence accumulated suggests that dNT are essential for the growth
      and maturation of the gut epithelia. In previous experiments we have documented
      immunoregulative properties of dNT-containing extracts. In this study Balb/c
      female mice were fed (1) standard diet, (2) dNT-supplemented diet, and (3) dNT
      supplemented water for 4 weeks. The supplement in dose of 100 mg/kg/l comprised
      original extract (Imuregen, Uniregen Ltd., Nachod, Czech Republic). Samples of
      terminal ileum in each dietary group were removed for histological examination.
      The length of villi was evaluated by computer morphometry. The highest growth of
      intestinal villi was observed in group administered dNT-supplemented water. We
      have found no pathological changes of intestinal epithelium in any experimental
      group.

PMID- 15568733
TI  - 1,3-Bis(2-hydroxyiminomethylpyridinium) propane as the potential reactivator of
      the acetylcholinesterase inhibited by nerve agents.
AB  - The oxime K005 [1,3-bis(2-hydroxyiminomethylpyridinium) propane dibromide] for
      the reactivation of the enzyme acetylcholinesterase (AChE) inhibited by
      cyclosarin and VX was tested. Its reactivation potency was not better in
      comparison with the currently used AChE reactivator--pralidoxime. On the other
      hand, the oxime K005 has its maximum reactivation ability at the concentration
      10(-4) M, which could be achieved for human use. The maximum concentration of
      pralidoxime was reached at the concentrations 10(-1) M (for cyclosarin) and 10(
      3) M (for VX) but these concentrations are not available for the use in vivo.

PMID- 15568734
TI  - Assessment of the therapeutic and anticonvulsive efficacy of a drug combination
      consisting of trihexyphenidyle and HI-6 in soman-poisoned rats.
AB  - 1. The influence of two anticholinergic drugs (atropine, trihexyphenidyle) on the
      effectiveness of antidotal treatment to eliminate soman-induced lethal effects
      and convulsions was studied in rats. 2. The oxime HI-6 when combined with
      centrally acting anticholinergic drug trihexyphenidyle seems to be more
      efficacious in the elimination of acute toxic effects of soman than its
      combination with atropine. 3. The findings support the hypothesis that the choice
      of the anticholinergic drug is important for the effectiveness of antidotal
      mixture in the case of antidotal treatment of soman-induced acute poisoning.

PMID- 15568735
TI  - Effects of two types of restraint stress on the spontaneous behaviour in rats.
AB  - Our previous findings suggested the existence of stressor-specific behavioural
      and cognitive responses in rats. In the present study, restraint stressor
      (immobilization, IMO) and restraint stressor combined with partial immersion of
      rats into water (IMO+C) were applied for 1 hour to Wistar male rats and their
      spontaneous behaviour was examined in the open field test. The classic
      behavioural parameters were recorded: crossing, rearing, and resting. When tested
      1 and 4 hours after IMO+C, animals exhibited strong suppression of locomotor and
      exploratory activity (crossing and rearing); partial inhibition of both
      behavioural variables was found after IMO. Thus, substantial differences were
      observed in dependence on the length of period between the end of stressor
      application and the start of testing. In testing performed one week later, the
      locomotor and exploratory activity levels of both IMO and IMO+C animals
      corresponded to the control ones. These data suggest a differential behavioural
      response to both used stressors that may result from their different proportion
      of psychical and physical components. In conclusion, our results provide other
      data for the support of differential effects of two types of restraint stressors
      on spontaneous behaviour of animals exposed to a novel environment.

PMID- 15568736
TI  - The multidrug resistance and apoptosis evaluation in acute myeloid leukemia cells
      after the in vitro doxorubicin treatment.
AB  - The apoptosis failure in cytostatic treatment of haemoblastosis is one of the
      means of chemoresistance. We were interested in the relationship of the after
      doxorubicin-treatment-AML cells apoptosis and the immunophenotype, selected
      clinical and laboratory parameters, and also the P-gp, MRP, LRP, Bcl-2, Bax
      proteins expression. All analysis were evaluated with the flow cytometry method.
      To detect apoptotic cells in the sample, we used three methods: annexin test,
      TUNEL (TdT-mediated dUTP nick end labeling) test, and caspase 8 detection. After
      the cell cultivation the statisticaly important increase of apoptotic cells in
      the culture was apparent. The relation between the AML blast in vitro reaction
      and some clinical parameters such as the age of patient, white blood cell count,
      and blast percentage was also observed.

PMID- 15568737
TI  - Excess of Pappenheimer bodies (siderocytes) in two splenectomized siblings with
      congenital dyserythropoietic anemia--type II (CDA-II) and iron overload.
AB  - In two splenectomized siblings with congenital dyserythropoietic anemia type-II
      (CDA-II) and iron overload excess of Pappenheimer bodies reaching 46.4% and 15.9%
      respectively was found. Cause, significance and differential diagnosis of this
      finding were discussed.

PMID- 15568738
TI  - Vitamin A and beta-carotene levels during pregnancy in Gaziantep, Turkey.
AB  - Vitamin A levels during pregnancy have important influences on the health of
      pregnant women and the growing fetus. Therefore, plasma vitamin A and beta
      carotene concentrations during pregnancy in Turkish women living in Gaziantep
      city were investigated in a prevalence study. Optimum sample size was determined
      as 252 for vitamin A deficiency and vitamin A and beta-carotene levels were
      examined in 427 pregnant women aged 14-44 years. Vitamin A and beta-carotene
      concentrations were measured spectrophotometrically by Neeld Pearson method.
      Vitamin A and beta-carotene concentrations in pregnant women were found as 1.14
      +/- 0.44 micromol/L, and 1.80 +/- 0.66 micromol/L, respectively. Plasma vitamin A
      concentrations were found in low levels (<1.05 micromol/L) in 45.5% of pregnant
      women. Vitamin A deficiency (<0.7 micromol/L) was determined in 16.9% of pregnant
      women. A mild negative correlation was obtained between the vitamin A
      concentration and pregnancy period. Vitamin A levels of pregnant women were
      decreased significantly in the third trimester (p<0.05). The findings of present
      study suggest that vitamin A levels of pregnant women were poor in the region.
      Therefore, the intake of vitamin A with foods should be improved. Supplementation
      of vitamin A might benefit at improving maternal and child health especially in
      high-risk groups especially in developing countries. Monitoring vitamin A levels
      in pregnant women is very important for also determining low and high levels.

PMID- 15568739
TI  - Human decidual cells activity in women with spontaneous abortions of probable CMV
      aetiology during the first trimester of gestation. An immunohistochemical study
      with CMV-associated antigen.
AB  - AIM: To determine the expression of CMV-associated antigen in the human decidual
      endometrial stromal cells in spontaneous abortions with no evidence of maternal
      relapse during the first trimester of gestation. EXPERIMENTAL DESIGN: We examined
      15 placentas resulting from intrauterine fetal death after spontaneous abortion
      during the 8th, 10th, and 12th week of gestation respectively, and in which CMV
      reactivation was ruled out from serological evaluation of the pregnant women at
      admission, versus equal controls after voluntary abortion following well
      documented maternal viral recurrence. In addition, a panel of monoclonal
      antibodies for the identification of leukocytes (CD45/LCA), B-lymphocytes (CD20/L
      26), and T-lymphocytes (CD45RO/UCHL1), was performed. All women received hormonal
      medication to support gestation, in the cases of spontaneous abortions. RESULTS:
      Immunohistochemical examination using a specific antibody against cytomegalovirus
      showed large multinucleated infected cells with intranuclear inclusions, located
      primarily in the decidual stroma within a lymphoplasmacytic infiltrate in the
      cases of spontaneous abortions. No evidence of infection was observed in the
      chorionic villi. In the cases of voluntary abortions same findings were observed
      in the relevant areas, and a strong evidence of infection was observed in the
      chorionic villi. CONCLUSION: This study demonstrates 1) that the decidual
      endometrial stromal cells can express the CMV-associated antigen prior to
      serological manifestation of the viral replication, 2) the expression of the
      antigen is higher in cases of hormonal administration to support gestation. In
      these cases a mild mononuclear infiltrate of UCHL1 (T marker) positive cells,
      accompanies the CMV-associated antigen positive cells.

PMID- 15568740
TI  - Butyrylcholinesterase-positive innervation of the spleen in rats.
AB  - Innervation of the spleen in rats was studied. Butyrylcholinesterase-(BuChE)
      positive nerve components of the organ were visualized by the direct thiocholine
      method. BuChE-positive nerve components enter the spleen in a common bundle with
      arteries. In the organ they form characteristic periarterial and periarteriolar
      plexiform arrangements, which are especially conspicuous around the aa. centrales
      running through the white pulp. Then, nerve fibres extend away from these
      plexuses into adjacent layers of trabeculae further into marginal layers of
      periarterial lymphatic sheath (PALS) as well as into the mantle zone of
      follicles. Several scattered periarteriolar and solitary nerve fibres can be seen
      in the marginal sinuses and cords of the red pulp. In the fibrous capsula BuChE
      positive nerve fibres can also be seen which have an evident connection with
      trabecular and parenchymal nerves of the organ. Microscopic findings support the
      notion that BuChE-positive nerve profiles supply not only the vasculature, but
      also the parenchymal components of the spleen, and they may participate, to a
      great extent, in the regulation of the immune processes in this organ.

PMID- 15568741
TI  - Acetylcholinesterase (AChE)-positive innervation of the guinea-pig spleen.
AB  - The presence and intraorgan distribution of the acetylcholinesterase (AChE)
      positive nerve structures in the guinea-pig spleen were studied by means of the
      direct thiocholine method. Visualized AChE-positive nerve fibres entered the
      guinea-pig spleen at its hilum in the vicinity of the splenic artery branches and
      intra parenchyma were gradually distributed to form thicker periarterial nerves
      and also fine adventitial nerve plexus. In described topography the AChE-positive
      nerve fibres were identified in association with the central artery running
      through the white pulp. Some of the perivascular nerve fibres associated with the
      central artery extended away and passed into the periarterial lymphatic sheath
      (PALS) to reach the marginal zone and in continuation entered into the mantle
      zone of lymphatic follicles. Several AChE-positive nerve fibres were seen in the
      red pulp but less in the splenic capsule. We did not find any AChE-positive nerve
      cells in the guinea-pig spleen.

PMID- 15568742
TI  - Visualization of protein aggregation in nerve cells after ischemia/reperfusion by
      ubiquitin immunohistochemistry and impregnative Nauta method.
AB  - Using ubiquitin immunohistochemistry and impregnative Nauta method we
      demonstrated that ubiquitin positivity and Nauta positivity in the neurons
      affected with ischemic injury in the lumbosacral spinal cord of rabbits and dogs
      may be of the same origin. Increased number of ubiquitin-positive aggregates was
      found in the cytoplasm of neurons in the intermediate zone and lamina IX of
      ventral horns of spinal cord in rabbits after 30 min of ischemia followed by 24 h
      lasting reperfusion. Nauta-positive, flocculent, intracytoplasmic, dark clusters
      appeared in the same localization in the canine lumbosacral spinal cord neurons
      after 30 min of ischemia and 24 h of reperfusion. Ubiquitin aggregates and Nauta
      positive dark clusters in the injured spinal cord neurons could be the first
      light microscopic signs of slow neuronal death following spinal cord ischemia and
      reperfusion.

PMID- 15568743
TI  - [Evaluation of methods for total nasal reconstruction].
AB  - OBJECTIVE: To evaluate the advantages, disadvantages and their indications of
      total nasal reconstruction with different techniques. METHODS: A series of total
      nasal reconstruction were treated with four methods from 1975 to 2003. These
      methods were tubed flap of arm,midline forehead flap with skin graft, midline
      forehead flap with bilateral frontotemporal flaps for repairing the donor site,
      and expanded forehead flap. RESULTS: All of the patients were treated
      successfully. The shape and function of the reconstructed noses were
      satisfactory. However, the traditional forehead flap with skin graft may leave a
      unsightly big and black scar on the forehead. The technique of the tubed flap of
      arm could provide enough tissue without remaining forehead scar and be easily
      shaped, but it required long period, multiple procedures and body fixation for
      three weeks. CONCLUSIONS: Midline forehead flap with bilateral frontotemporal
      flaps for repairing the donor site may be good for small nose reconstruction
      while expanded forehead flap could reconstruct a big nose. Tubed flap of arm may
      be used to the patients who do not wish to leave any scar on the forehead.
      Forehead flap with skin graft to repair the donor sit- should generally be
      avoided for nose reconstruction.

PMID- 15568744
TI  - [Application of iliac cancellous and chondral bone to repair the cleft of
      alveolar process and the nasal deformity at the same time].
AB  - OBJECTIVE: To study a new method of simultaneous repair of alveolar cleft and the
      deformity of the nose and lip. METHODS: 42 patients with cleft of alveolar
      process were included in this study. We filled the cleft of alveolar process with
      iliac cancellous bone and covered the depression of piriform aperture and the
      nasal side with iliac cartilage. Simultaneously, we corrected the nasal deformity
      using V-Y plasty of a mucosa-cartilage compound flap at the nasal vestibule.
      RESULTS: In the patients aged 9 approximately 11 years, the mean height of the
      repaired alveolar process was 86.7%; the mean thickness was 89.6%; the contour
      and function of the alveolar process was grade I or II. The canine erupted at the
      place of bone grafting. The depression of the piriform aperture and alae nasi was
      repaired. The contour of the nares was symmetrical. In the patients over 12
      years, the mean height of the alveolar process was 70.1%; the mean thickness was
      71.7%; the contour and function of the alveolar process was grade II or III. The
      deflexion of nasal dorsum and nasal dome was not ameliorated in 2 patients of 18
      years old. CONCLUSIONS: The application of iliac cancellous and chondral bone to
      simultaneously repair cleft of alveolar process and the nasal deformity is an
      ideal plastic method. It can recover the height of alveolar process and the
      continuity of dental arch, ameliorate the nasal deformity, and redress the
      deflexion of nasal dorsum and nasal end. It can also eliminate the psychological
      obstacle of the patients at an early stage.

PMID- 15568745
TI  - [3D image analysis of nasal orbit fossa through a laser scanner: a new method and
      application of 3D image].
AB  - OBJECTIVE: This study was to introduce the method for obtaining accurate 3D data
      of soft tissues using a 3D scanner under non-contact condition and the standard
      3D measurement of the nasal orbit fossa for plastic surgery. METHODS: A 3D laser
      scanner and the Geomagic software were used to obtain the standard facial contour
      of 30 Chinese people. The nasal orbit fossa, as the feature of beauty, was
      measured and the data were analyzed. RESULTS: 3D measurement exhibited the three
      dimensional facial shape at every meaningful angle, with the advantages of high
      precision of 0.01 mm. We determined the lowest point and described the 3D feature
      of the nasal orbit fossa. CONCLUSIONS: This method can illustrate the relation of
      the nasal orbit fossa and the surrounding structure. It is a new approach to
      facilitate preoperative plans, operation simulation and postoperative evaluation.

PMID- 15568746
TI  - [Application and review of the reversed posterior interosseous artery flap in 78
      clinical cases].
AB  - OBJECTIVE: To assess and review the indications and methods of the reversed
      posterior interosseous artery flap for repairing soft tissue defects of the hand.
      METHODS: In the series, three types of flaps were utilized including the reversed
      posterior interosseous artery flap, the expanded reversed posterior interosseous
      artery flap and the reversed posterior interosseous artery conjoint flap. 78
      clinical cases were treated with this method, in which 12 cases used the expanded
      reversed posterior interosseous artery flap and 10 cases used the reversed
      posterior interosseous artery conjoint flap. The flap,ranged from 8 approximately
      6 cm to 14 approximately 8 cm, was used to repair the defects of the dorsal hand
      as far as to the fingerweb. The anatomy of the posterior interosseous artery was
      observed in the surgical dissection. RESULTS: The posterior interosseous artery
      was consistently identified in all the 78 cases. In 4 cases, the artery
      terminated in the middle third of the dorsal forearm, therefore an alternative
      method of reconstruction was used. In the 53 cases of reversed posterior
      interosseous flaps, 49 cases healed uneventfully and 4 cases suffered necrosis in
      the distal border of the flap, but subsequently healed spontaneously. 12 cases of
      expanded flaps survived well and the donor sites were directly approximated. In
      the 9 cases of conjoint flaps based on the posterior interosseous artery, 7 cases
      healed uneventfully and 2 cases suffered delayed healing because of flap necrosis
      of the distal part. The satisfactory appearance and hand function were achieved
      postoperatively in all cases. CONCLUSIONS: The flap is a better choice for
      repairing the soft tissue defects of the hand. The different type of flaps can be
      selected to meet the clinical requirements of reconstruction. It is suggested
      that the artery variation should be assessed preoperatively.

PMID- 15568747
TI  - [The design of the expanded flap for the repair of the temporal and cheek area].
AB  - OBJECTIVE: To explore the design of an expanded flap at the temporal and cheek
      area. METHODS: The expanded flap was used for the repair of 619 temporal and
      cheek defects secondary to scar, nevus or hemangioma excision. In the frontal
      area, the rotational flap was usually used. For the repair of the cheek, the
      applied flap included the rotational, advanced, and transposition flap from the
      neck, as well as the pedicle flap from the thoracic area. RESULTS: Eight thoracic
      deltoid flaps had distal necrosis of 1 approximately 5 cm. Of them, 5 flaps were
      repositioned with subsequent good result; the other 3 flaps underwent skin
      grafting. The five facial expanded flaps showed distal necrosis of 0.5
      approximately 1 cm. Of them, 4 flaps occurred delayed healing, 1 flap underwent
      skin grafting. Expander extrusion happened in 41 cases (6.62%), which resulted in
      deficiency of the expanded area. Satisfactory results were achieved in all the
      other cases. CONCLUSIONS: According to our experience, careful design of the flap
      is very important for obtainingbetter surgical results and decreasing
      complications.

PMID- 15568748
TI  - [Microvascular study of the transmidline scapular flap vascularized by the
      contralateral circumflex scapular artery].
AB  - OBJECTIVE: To observe the microvascular distribution of the transmidline scapular
      flap supplied by the contralateral circumflex scapular artery. METHODS: The
      integument and deep tissues of 6 fresh cadavers were dissected and radiographed
      after vermilion mixture was injected to the unilateral circumflex scapular
      artery. RESULTS: The vascular tree passed the midline and reached to the
      contralateral acromion. The vessel density was the highest in the irrigating side
      of the back, which was higher in the middle area. In the contralateral side,the
      high vessel density concentrated in the upper part of the back. CONCLUSIONS: The
      result revealed the direct evidence for the clinical application of the
      transmidline scapular flap. In design and elevating of the transmidline scapular
      flap, it should be slanting to the upper part of the contralateral back.

PMID- 15568749
TI  - [The expression and interaction of cyclin D1 and p16 in fibroblasts of pathologic
      scars].
AB  - OBJECTIVE: To investigate the expression of cyclin D1, p16, AR and ER in
      fibroblasts of scars for further understanding the interaction of these factors
      and the roles that they play in scar development. METHODS: Thirty samples of
      mature scar, hypertrophic scar and keloid were detected with immunohistochemical
      method (SP technique) and compared with normal skin. RESULTS: There were on
      positive results in normal skin and mature scars. The expression of cyclin D1,
      p16 and AR was higher in hypertrophic scars and keloids than in normal skin with
      significant difference (P < 0.05). The expression of cyclin D1 in keloids was
      higher than in hypertrophic scars (P < 0.05). Though the expression of p16 was
      higher in keloids than in hypertrophic scars, the difference was not significant.
      There was significant correlation between the expression of cyclin D1 and AR in
      the pathologic scar. CONCLUSION: The AR played an important role in scar
      formation and displayed its function through cyclin D1. The expression of p16
      could suppress the excessive proliferation of cells to some extent. If the effect
      was not enough to resist the function of cyclin D1, long-term proliferation of
      cells would occur and lead to keloid formation. As the expression of cyclin D1
      and p16 in hypertrophic scars was in a state of relative equilibrium, the cell
      proliferation showed a tendency of self-restriction.

PMID- 15568750
TI  - [Experimental study on apoptosis of keloid-derived fibroblast transducted with
      Fas gene by recombinant adenovirus].
AB  - OBJECTIVE: To generate recombinant adenovirus with human Fas gene and transfect
      the Fas gene into keloid-derived fibroblasts to replace the dysfunctional Fas
      gene for reconstruction of the blocked Fas signal. METHODS: Fas gene was cut down
      from the PcDNA3.1-Fas plasmid. The recombinant adenovirus vector was constructed
      using PDC 315 system. Then the expression and function of the transfected Fas
      gene was detected. RESULTS: We successfully constructed the recombinant
      adenovirus vector with Fas gene and detected its expression and function in the
      infected keloid-derived fibroblasts. CONCLUSION: We have successfully generated
      recombinant adenovirus (Ad-PDC315-Fas), which can transfect the Fas gene into
      keloid-derived fibroblasis to replace the dysfunctional Fas gene and reconstruct
      the blocked Fas signal. The correlation between the keloid and Fas gene was
      confirmed. The result may set up a sound foundation for gene therapy of keloid.

PMID- 15568751
TI  - [Expression and significance of alpha5beta1 integrin in abnormal scars].
AB  - OBJECTIVE: To study the expression of alpha5beta1 integrin in the abnormal scars
      and its role and significance in the formation and development of abnormal scars.
      METHODS: The expression of alpha5beta1 integrin was observed in hypertrophic scar
      (15 samples), keloid (15 samples) and normal skin (10 samples) with SP
      immunohistochemical method and colloidal gold immuno-electron microscopic
      technique. The data were semi-quantitatively analyzed. RESULTS: The expression
      levels of alpha5beta1 integrin in the fibroblasts of keloids and hypertrophic
      scars were higher than normal skin; the expression of alpha5beta1 integrin in the
      fibroblasts of keloids was higher than hypertrophic scars (P < 0.01). CONCLUSION:
      The alpha5beta1 integrin appears to have close relation to the formation and
      development of abnormal scars. To find a way to decrease the expression level of
      alpha5beta1 integrin in fibroblasts may be a new approach to inhibit scar
      hypertrophy.

PMID- 15568752
TI  - [Experimental study of a polypropylene mesh for moulding and supporting a breast
      during a breast reduction procedure].
AB  - OBJECTIVE: To study the polypropylene mesh acted for the moulding and support.
      METHODS: Four mini-pigs were used in this experimental research. A polypropylene
      mesh was implanted under the skin on one side of each pig. An expander was
      thereafter placed in the deep layer to imitate the action of gravity to the skin
      and mesh. The specimens were collected in two different times for the
      biomechanics and histology examinations. RESULTS: The biomechanical data were
      shown lower and the histological properties were found changeable in the expanded
      skin without the mesh support, compared with the normal skin. However, the
      changes did not occur in the expanded skin with the mesh support. Furthermore,
      the tensile strength and elastic modulus of the polypropylene mesh were
      significant less than the human skin. CONCLUSION: The Polypropylene mesh could
      prevent the extended skin effectively and has moulding and support effects.

PMID- 15568753
TI  - [The neuro-vascular anatomical study of breast and it's signification in
      reduction mammaplasty].
AB  - OBJECTIVE: to investigate the pattern of the blood supply and the nerve
      distribution of breast, in order to find a way for short-scar reduction
      mammaplasty. METHODS: Twelve adult women cadavers were investigated for the
      vascularture of the anterior thorax and the nerve distribution of the breasts by
      using the blood vessel casting, specimen transparency technique and the autopsy.
      Based on the anatomical study, a modified double-circle reduction mammaplasty
      technique was designed to treat 28 patients with hypertrophical breasts. RESULTS:
      There existed two- or three-layers vasculature in the anterior thorax. The
      extensive vertical vascular anastomoses were found among the three layers. The
      cutaneous perforators, penetrated out of the pectoralis major muscle, were formed
      a dense vessel network in the retromammary space. The vertical vessels thereafter
      emerged from the network, passed through gland and linked to the subcutaneous
      vessels. These vertical vessels were smaller and denser above the fourth
      intercostal space, but they were larger and sparser below the fourth intercostal
      space. The innervation of the nipple-areola mainly came from the lateral deep
      branches of the 4th intercostal nerve. It appeared S-shape running into the
      dropped breasts. The 28 patients were successfully treated with the modified
      technique, except one case with the loss of the nipple-areola sense. CONCLUSION:
      The modified double-circle reduction mammaplasty could maximally fulfill the
      blood supply to the remained gland and the innervations to the nipple-areola, by
      keeping the advantages of the traditional technique such as invisible scar, good
      projection and the long lasting results. It could also be a safe and reliable
      technique.

PMID- 15568754
TI  - [Breast reconstruction with multiple miniprostheses].
AB  - OBJECTIVE: To evaluate a new technique for breast reconstruction with multiple
      miniprostheses, METHODS: Each silicone miniprosthesis(10 approximately 15 ml) was
      implanted one by one beneath the prepared muscle pocket until the desired volume
      was achieved. RESULTS: Seven patients were treated with the above mentioned
      technique, including five after gland fibroadenoma excision, one hemangioma
      excision and one reduction mammoplasty. The results were satisfactory.
      CONCLUSION: The above mentioned technique with the miniprostheses may be another
      good way for breast augmentation and breast reconstruction with many advantages
      such as smaller incision, easy intraoperative assessment of the ideal size of the
      breast, easy handling the technique, perhaps low incidence of capsular
      contracture.

PMID- 15568755
TI  - [Sulcus evaluation after repairing bilateral alveolar clefts with bone graft in
      different techniques].
AB  - OBJECTIVE: To evaluate the sulcus depth changes of bilateral alveolar clefts
      after bone grafting with different techniques. METHODS: Forty-two patients with
      bilateral alveolar clefts were treated in the Department of Oral and
      Maxillofacial Surgery of Xiangya Hospital, Central South University, including
      three bilateral alveolar clefts with bilateral cleft lips and thirty-nine
      bilateral alveolar clefts with bilateral complete cleft lip and cleft palate.
      Three techniques were used to repair the bilateral alveolar clefts, named: bucket
      handle mucosal flap, bilateral buccal mucosal flaps and bilateral buccal mucosal
      flaps with premaxillary separation and bone grafting. Postoperatively, the depth
      of the sulcus was evaluated with the following four grades: 0) no change, I) one
      third shallow, II) two-thirds shallow, III) disappear. RESULTS: Forty-two
      bilateral alveolar clefts were repaired with the above mentioned techniques with
      the results: Grade 0 in 20 patients (47.6%), grade I in 10 patients (23.8%),
      grade II in 10 patients (23.8%), grade III in 2 patients (4.7%). In 6 patients
      with the bucket-handle mucosal flap technique and the technique of the bilateral
      buccal mucosal flaps with the premaxillary bone graft, the depth of the sulcus
      was reduced to two-thirds in 4 patients (66.7%), and the sulcus totally
      disappeared in 2 patients (33.3%). CONCLUSIONS: The above mentioned techniques
      could reduce the depth of the sulcus, therefore, the surgeons should notice this
      complication and prevent it during the operation.

PMID- 15568756
TI  - [The rectus abdominis musculoperitoneal composite flap for tongue reconstruction
      following extensive resection of cancer: a report of 2 cases].
AB  - OBJECTIVE: To explore the possibility of tongue reconstruction following cancer
      resection by a rectus abdominis musculoperitoneal composite flap. METHODS: Half
      tongue defect was reconstructed using the rectus abdominis musculoperitoneal
      composite free flap in 2 patients. RESULTS: The postoperative period was
      uneventful and complete survival of the flap was occurred in the 2 cases. The
      reconstructed tongue showed excellent color match and natural shape. CONCLUSIONS:
      The rectus abdominis musculoperitoneal composite flap can be used for tongue
      defect reconstruction, especially when the defect was not more than half of the
      tongue.

PMID- 15568757
TI  - [Correction of cupped ear by using a stainless steel wire suspension technique].
AB  - OBJECTIVE: To evaluate a new reliable surgical technique for correction the
      congenital cupped ear. METHODS: With 96 patients, a stainless steel wire was
      introduced to suspend auricular cartilage on the pericranium after the cupped ear
      was corrected. The follow-ups were carried out after the operation. RESULTS: Up
      to 3 years follow-ups with 52 cases, the results were satisfactory and durable.
      CONCLUSIONS: The above mentioned technique could be a reliable way to correct
      mild and moderate cupped ear abnormalities.

PMID- 15568758
TI  - [Endoscope-assisted parotidectomy for benign tumors via a short hidden auricular
      incision].
AB  - OBJECTIVE: To evaluate a technique of endoscope-assisted parotidectomy for benign
      tumor via a short hidden auricular incision. METHODS: Twenty-six volunteer
      patients were selected for the new approach, 16 with mixed tumor, 9 Warthin's
      tumor and 1 lymphoepithelial cyst. The tumor size was 1.6 approximately 3 cm
      (average 2.2 cm) and the incision ranged 3.5 approximately 5.5 cm(average 4.5cm)
      divided into two parts: 1) basic segment--started from anterio-superior crease of
      tragus, went downward along tragal margin and pre-earlobial fold,and stopped at
      earlobe root; 2) extended segment--went from earlobe root, curved down posterio
      inferiorly. The length of the latter was generally not beyond 1 cm. The procedure
      began with raising the myo-cutaneous flap and dissecting the whole posterior
      portion of the gland. Thus, two working spaces needed for endoscopic manipulation
      could be artificially created with suitable retracting instruments. Endoscopic
      view was then established, and the surgeons operated continuously in the later
      steps. Modified techniques, such as the antegrade facial nerve dissection,
      retrograde great auricular nerve dissection and direct coagulate-cut method with
      ultrasonically activated scalpel, were employed to archive the goals of
      endoscopical nerve preservation and tissue resection. RESULTS: All tumors were
      entirely removed. No postoperative paralysis occurred, excepting 1 case who
      suffered from an temporary paralysis for two months. The appearance was good due
      to overlapping the short scar onto the irregular line of auricular contour and
      hiding its lowest part in the earlobe shadow. CONCLUSIONS: Parotidectomy for
      benign tumors could be safely done via a much-shortened incision, assisted by an
      endoscope. The postoperative stress of patients can be obviously reduced with the
      minimally invasive manipulation and the good appearance.

PMID- 15568759
TI  - [Clinical study of chest development after costal cartilage harvesting in
      children].
AB  - OBJECTIVE: To evaluate the development of the chest wall after costal cartilage
      harvesting in children. METHODS: Thirty-nine patients, who underwent microtia
      reconstruction with costal cartilage grafts, were examined in the donor-site with
      physical examination and radiography. Forty normal children were selected as
      control. RESULTS: There were no significant differences in size between the
      bilateral chests, and compared to the control. The rib deformity in each donor
      site was not observed on the radiography. CONCLUSIONS: The costal cartilage
      harvesting in children has no significant evidence to influence the development
      of the chest wall.

PMID- 15568760
TI  - [Minimizing the antigenicity of tracheal allografts by using a technique of
      cryopreservation].
AB  - OBJECTIVE: To investigate the proper time of cryo-preserving tracheal allograft
      so as to minimize its antigenicity. METHODS: On a dog model, this study was
      carried out by allografting a tracheal into a muscular flap formed with
      sternocephalic muscle and sternohyoid--sternothyroid muscle. The tracheal was
      treated with cryopreservation in defferent intervals. The viability of the graft
      was evaluated by the examination of fiberoptic bronchoscopy, histopathology and
      microangiography. The blood flow of the tracheal mucous was measured with a blood
      flowmeter and the survival area was decided in the calculation of the percentage.
      RESULTS: There are no significant differences in the mucous membrane appearance
      and the mucosal blood flow one week after the surgery among the non
      cryopreservation group and the groups treated with cryopreservation in 1 day, 2
      weeks, 4 weeks, 6 weeks and 8 weeks. The graft was found to start necrosis 2
      weeks after the transplantation with the infiltration of mononuclear cells
      examined under light microscope in almost all of the groups, especially in the
      non-cryopreservation group and the groups treated with cryopreservation in 1 day,
      2 weeks. However, there was no significant difference among the autograft group
      and the allograft groups cryopreservated in 6 weeks and 8 weeks, and the
      infiltration of the mononuclear cells was not found in these groups either.
      CONCLUSION: The antigenicity of the tracheal allografts could be significantly
      decreased by the treatment of cryopreservation over 6 weeks.

PMID- 15568761
TI  - Mechanism-based inactivation of COX-1 by red wine m-hydroquinones: a structure
      activity relationship study.
AB  - Resveratrol (1) is a m-hydroquinone found in red wine, which has
      antiinflammatory, cardiovascular protective (antiplatelet), and cancer
      chemopreventive properties. It is a potent peroxidase-dependent mechanism-based
      inactivator of COX-1, a desired target for antiplatelet agents, and has no
      similar effect on COX-2. Much attention has focused on resveratrol (1) as being
      the sole agent responsible for the cardioprotective effects associated with red
      wine consumption (commonly known as the "French paradox"). In this study we show
      that other red wine constituents, namely, the catechins (2, 3) and epicatechins
      (4, 5), act as peroxidase mediated mechanism-based inactivators of COX-1 but not
      of COX-2. Structure-activity relationships identify these agents as being as
      effective as resveratrol with respect to their ability to specifically inactivate
      COX-1. We show that resorcinol (6) is the minimum structure necessary for
      mechanism-based inactivation of COX-1. These findings imply that resveratrol is
      not the sole agent responsible for the antiplatelet activity of red wine and
      suggest that all dietary m-hydroquinones should be examined for cardioprotective
      effects.

PMID- 15568762
TI  - Benzoic acid derivatives from Piper species and their fungitoxic activity against
      Cladosporium cladosporioides and C. sphaerospermum.
AB  - Piper crassinervium, P. aduncum, P. hostmannianum, and P. gaudichaudianum contain
      the new benzoic acid derivatives crassinervic acid (1), aduncumene (8),
      hostmaniane (18), and gaudichaudianic acid (20), respectively, as major secondary
      metabolites. Additionally, 19 known compounds such as benzoic acids, chromenes,
      and flavonoids were isolated and identified. The antifungal activity of these
      compounds was evaluated by bioautographic TLC assay against Cladosporium
      cladosporioides and C. sphaerospermum.

PMID- 15568763
TI  - Six new diterpenoids from Suregada multiflora.
AB  - Six new diterpenoids were isolated from a CH(2)Cl(2)-MeOH extract of the bark of
      Suregada multiflora. The structures were established on the basis of one- and two
      dimensional NMR and other spectroscopic studies and chemical derivatizations. Two
      compounds, suregadolides C (1) and D (2), were identified as new diterpene
      lactones of two antipodal series, containing a cyclopropane ring bridging C-3 and
      C-4 of the basic abietane skeleton. Suremulide A (3) was found to be a new
      abietene diterpene lactone. Bannaringaolide A (4), a diterpene lactone, based on
      a novel carbon skeleton with a seven-membered ring, possibly formed by the
      rearrangement of the exocyclic C-17 in ring C of an ent-pimarane framework, has
      also been isolated. A kaurane triol, suremulol A (5), and a kaurane diol,
      suremulol B (6), were also identified as new metabolites.

PMID- 15568764
TI  - Anti-inflammatory phloroglucinols and terpenoids from Garcinia subelliptica.
AB  - Three new phloroglucinols, garcinielliptones K (1), L (2), and M (3), and two new
      terpenoids, garcinielliptones N (4) and O (5), have been isolated from the seeds
      of Garcinia subelliptica. The structures of 1-5 including their relative
      configurations were elucidated by spectroscopic methods and supported by computer
      generated molecular modeling. Compounds 2 and 3 showed potent inhibitory effects
      on the release of beta-glucuronidase, and on beta-glucuronidase and histamine,
      respectively, from peritoneal mast cells stimulated with p-methoxy-N
      methylphenethylamine (compound 48/80) in a concentration-dependent manner.
      Compounds 2 and 3 showed potent effects on NO production in culture media of RAW
      264.7 cells in response to lipopolysaccharide (LPS). Compound 2 also showed a
      potent effect on NO production in culture media of N9 cells in response to
      LPS/interferon-gamma (IFN-gamma).

PMID- 15568765
TI  - Quinolone alkaloids with nitric oxide production inhibitory activity from Orixa
      japonica.
AB  - Four new quinolone alkaloids, orixalone A (1), B (2), C (3), and D (4), together
      with 12 known compounds were isolated from the stems of Orixa japonica. Orixalone
      A (1) inhibited nitric oxide production in murine macrophage-like RAW 264.7 cells
      stimulated with interferon-gamma and lipopolysaccharide.

PMID- 15568766
TI  - Montacin and cis-montacin, two new cytotoxic monotetrahydrofuran annonaceous
      acetogenins from Annona montana.
AB  - Two new monotetrahydrofuran Annonaceous acetogenins, montacin (1), and cis
      montacin (2), along with four known acetogenins, annonacin, cis-annonacin,
      annomontacin, and cis-annomontacin, were isolated from the seeds of Annona
      montana. The structures of the new isolates were elucidated by spectral and
      chemical methods. The new acetogenins exhibited moderate in vitro cytotoxic
      activity against the 1A9 human ovarian cancer cell line. Interestingly, when
      Ca(2+) was present, compounds 1 and 2 became 3- to 10-fold more active against
      1A9 cells and the PTX10 subline.

PMID- 15568767
TI  - New luffariellolide derivatives from the Indonesian sponge Acanthodendrilla sp.
AB  - Investigation of the Indonesian sponge Acanthodendrilla sp. afforded five new
      luffariellolide-related sesterterpenes, acantholides A-E (1-5), in addition to
      luffariellolide and its 25-O-methyl and 25-O-ethyl derivatives. All structures
      were unambiguously established by 1D and 2D NMR and MS spectroscopy. Acantholide
      D and E are derivatives comprising the 1-acetylcyclopentan-5-ol moiety, which are
      new variants of the C(14)-C(20) segment for this type of linear sesterterpenes.
      Luffariellolide and its 25-O-methyl congener as well as acantholide E (5) were
      cytotoxic against the mouse lymphoma L5187Y cell line. Acantholide B (2),
      luffariellolide, and its 25-O-methyl congener were active against the Gram
      positive bacteria Staphylococcus aureus and Bacillus subtilis, the Gram-negative
      bacterium Escherichia coli, the yeast Candida albicans, and the plant pathogenic
      fungus Cladosporium herbarum.

PMID- 15568768
TI  - A new glucosyl feruloyl quinic acid as a potential marker for roots and rhizomes
      of goldenseal, Hydrastis canadensis.
AB  - A new compound, 5-O-(4'-[beta-d-glucopyranosyl]-trans-feruloyl)quinic acid (GPFQ,
      10), is reported from the medicinal plant goldenseal (Hydrastis canadensis). A
      new HPLC method is described and used to show that GPFQ is a potential marker for
      goldenseal roots (1.0% w/w) and rhizomes (2.3%). GPFQ was found at much lower
      levels in stems (<0.1%) and could not be detected in leaves. Neochlorogenic acid
      (9), which has not previously been reported from goldenseal, and chlorogenic acid
      (6) reached their highest levels in leaves (0.9% 9 and 0.5% 6). The main
      alkaloids, hydrastine (1) and berberine (2), were highest in rhizomes (2.8% 1 and
      4.6% 2), but palmatine (5) was not found in genuine goldenseal.

PMID- 15568769
TI  - Cucurbitane triterpenoids from Leucopaxillus gentianeus.
AB  - In addition to the known bioactive triterpene cucurbitacin B (1), two new
      cucurbitane triterpenoids, namely, leucopaxillones A (3) and B (4), exhibiting a
      new oxygenation pattern among cucurbitacins, have been isolated from the mushroom
      Leucopaxillus gentianeus (syn. L. amarus). Cucurbitacin B (1) imparts a bitter
      taste to the flesh of the fungus; however, it occurs in the fruiting bodies
      mainly esterified as tasteless fatty acid esters 2a-c. In vitro growth inhibitory
      effects of compounds 1-4 on proliferation of four different human tumor cell
      lines (A549, CAKI-1, HepG2, MCF-7) were evaluated by using a 1-day MTT assay.
      Only cucurbitacin B was highly active on all lines. Free cucurbitacin B is
      presumed to be formed in vivo by an enzyme-mediated scission of esters 2a-c, thus
      constituting a chemical weapon that protects the mushrooms against parasites and
      predators. Compounds 1-4 are structurally different from the other few
      cucurbitacins isolated from Basidiomycetes, being, instead, more similar to those
      occurring in plants. In particular, cucurbitacin B (1) seems to represent an
      interesting example of secondary metabolite convergence between distant taxa such
      as fungi and vascular plants, where they likely exert a similar role of
      protection. The structures of the compounds were established by means of
      spectroscopic methods and X-ray diffraction on a single crystal. The absolute
      configuration of leucopaxillone A has been assigned on the basis of CD chirality
      rules.

PMID- 15568770
TI  - Estrogenic and anticarcinogenic properties of kurarinone, a lavandulyl flavanone
      from the roots of Sophora flavescens.
AB  - Kurarinone, a lavandulyl flavanone, was isolated from a polyphenolic extract of
      the roots of Sophora flavescens using fractionation guided by estrogenic
      activity, which was determined by recombinant yeast and Ishikawa Var-I bioassays.
      Kurarinone showed weak estrogenic activity both in the yeast screen and in the
      Ishikawa Var-I assay with EC(50) values of 4.6 and 1.66 microM, respectively.
      Furthermore, kurarinone was found to have potent cytotoxic activity (IC(50) value
      = 22.2 microM) against human MCF-7/6 breast cancer cells in the sulforhodamine-B
      assay.

PMID- 15568771
TI  - Iridoid glucosides and p-coumaroyl iridoids from Viburnum luzonicum and their
      cytotoxicity.
AB  - Four new iridoids glucosides (1-4) and seven new iridoid aglycons (5-11) bearing
      (E)- or (Z)-p-coumaroyl groups were isolated from a methanol extract of the dried
      leaves of Viburnum luzonicum collected in Kaoshiung, Taiwan. The structures of
      the new compounds, named luzonoside A (1), luzonoside B (2), luzonoside C (3),
      luzonoside D (4), luzonoid A (5), luzonoid B (6), luzonoid C (7), luzonoid D (8),
      luzonoid E (9), luzonoid F (10), and luzonoid G (11), were elucidated by analysis
      of spectroscopic data and comparison with values for previously known analogues.
      Among the iridoids isolated in the present study, glucosides 1 and 2, and their
      aglycons 5-9, exhibited moderate inhibitory activity against HeLa S3 cancer
      cells, whereas 3 and 4 showed no cytotoxicity even at 100 microM.

PMID- 15568772
TI  - Isolation of cytochrome P450 inhibitors from strawberry fruit, Fragaria ananassa.
AB  - A new glycoside, 2-beta-d-glucopyranosyloxy-4,6-dihydroxyisovalerophenone (3),
      was isolated from strawberry fruit along with kaempferol-3-beta-D-(6-O-trans-p
      coumaroyl)glucopyranoside (1) and kaempferol-3-beta-D-(6-O-cis-p
      coumaroyl)glucopyranoside (2). Compounds 1 and 2 inhibited activity of a drug
      metabolizing enzyme, CYP3A4.

PMID- 15568773
TI  - N-inversion-associated conformational dynamics is unusually rapid in morphine
      alkaloids.
AB  - (13)C DNMR studies of codeine and sinomenine (derivatives of N-Me morphinan)
      indicated that N-inversion-C-N rotation (NIR) is unusually fast for these
      substituted piperidines when compared with other N-Me piperidines. Since only
      broadening, but no signal splitting, was reached at low temperatures and the
      difference of chemical shifts (Delta delta) for individual conformers with the
      equatorially and axially oriented N-Me substituent was unavailable, the limits of
      the NIR barrier for these amines were determined by line shape analysis using
      Delta delta values provided by ab initio calculations. On the basis of the
      comparison of experimentally determined (13)C NMR chemical shifts for tropane
      conformers with the ones calculated at different theory levels for this N-Me
      piperidine, the B3LYP/6-31G(p)/GIAO level was chosen as a sufficiently accurate
      method for calculations of Delta delta. By this new "semiempirical" procedure of
      line shape analysis the NIR barrier for the studied morphinans lies within a 25
      27 kJ mol(-1) (6.0-6.5 kcal mol(-1)) range. A low NIR barrier for morphine
      alkaloids is supposed to be an important factor in the activation of morphine
      receptor.

PMID- 15568774
TI  - Corymbiferan lactones from Penicillium hordei: stimulation of novel phenolic
      metabolites using plant tissue media.
AB  - Cultivation of a strain of Penicillium hordei on macerated tulip tissue agar
      resulted in the stimulated production of a series of four novel hydroxymethyl
      naphthalene carboxylic acid lactones from the fungus. The naphthalene derivatives
      were isolated using a combination of vacuum liquid chromatography and preparative
      HPLC. Their structures were determined by 1D and 2D NMR techniques in conjunction
      with high-resolution electrospray mass spectrometry (HRESIMS). These metabolites
      were given the trivial names corymbiferan lactones A-D (1-4).

PMID- 15568775
TI  - Farinosones A-C, neurotrophic alkaloidal metabolites from the entomogenous
      deuteromycete Paecilomyces farinosus.
AB  - Two new yellow pigments, farinosones A (1) and B (2), were isolated from the
      mycelial extract of the entomogenous fungal strain Paecilomyces farinosus RCEF
      0101, together with farinosone C (3), a new metabolite derived from an early step
      of pyridone alkaloid biosynthesis. The structures were determined by
      spectroscopic means, in particular by extensive NMR experiments. Compounds 1 and
      3 induced neurite outgrowth in the PC-12 cell line at concentrations of 50
      microM, while compound 2 was inactive. No cytotoxicity was observed for compounds
      1-3 in PC-12 cells when tested at 50 microM concentration in the MTT assay.

PMID- 15568776
TI  - Cassane- and norcassane-type diterpenes of Caesalpinia crista from Myanmar.
AB  - From the CH(2)Cl(2) extract of seed kernels of Caesalpinia crista from Myanmar,
      five new cassane-type diterpenes, caesalpinins MA-ME (1-5), and three new
      norcassane-type diterpenes, norcaesalpinins MA-MC (6-8), have been isolated,
      together with 12 known cassane-type diterpenes, 14(17)-dehydrocaesalmin F,
      caesaldekarin e, caesalmin B, caesalmin C, caesalmin E, 2-acetoxy-3
      deacetoxycaesaldekarin e, 2-acetoxycaesaldekarin e, caesalpinin C, 7
      acetoxybonducellpin C, caesalpinin E, norcaesalpinin B, and 6-acetoxy-3
      deacetoxycaesaldekarin e. The structures of the isolated compounds were
      elucidated by analysis of their spectroscopic data.

PMID- 15568777
TI  - Taxanes from rooted cuttings of Taxus canadensis.
AB  - A 3,11-cyclotaxane (1), a new epoxytaxane (2), an abeo-taxane (3), and 26 known
      taxanes were isolated in rooted cuttings of the Canadian yew (Taxus canadensis)
      for the first time. Their chemical structures were characterized as 1 beta,2
      alpha,9 alpha-trihydroxy-10 beta-acetoxy-5 alpha-cinnamoyloxy-3,11-cyclotaxa
      4(20)-en-13-one (1), 2 alpha,9 alpha,10 beta-triacetoxy-11,12-epoxy-20
      hydroxytaxa-4-en-13-one (2), and 7 beta,9 alpha,10 beta,13 alpha-tetraacetoxy
      11(15-->1)abeo-taxa-4(20),11-diene-5 alpha,15-diol (3). Metabolite 2 is a new
      taxane, metabolite 1 has been reported previously in the needles of Taxus
      baccata, and metabolite 3 was previously discovered as a biotransformation
      product but is now reported as a natural product for the first time.

PMID- 15568778
TI  - Prenylated benzophenones and xanthones from Hypericum scabrum.
AB  - Two new polyprenylated benzophenones, a new polyprenylated phloroglucinol, and
      six new xanthone derivatives were isolated from the aerial parts of the
      Uzbekistan medicinal plant Hypericum scabrum. Their structures were elucidated on
      the basis of spectroscopic evidence. The isolated compounds showed moderate
      cytotoxicity for human tumor cells.

PMID- 15568779
TI  - Biotransformation of nobiletin by Aspergillus niger and the antimutagenic
      activity of a metabolite, 4'-hydroxy-5,6,7,8,3'-pentamethoxyflavone.
AB  - Biotransformation of nobiletin (1) by Aspergillus niger has been investigated,
      and the product obtained was determined as 4'-hydroxy-5,6,7,8,3'
      pentamethoxyflavone (2). Antimutagenic activity of compound 2 was found, which
      showed suppressive effects on umu gene expression of the SOS response to DNA
      damage in Salmonella typhimurium TA1535/pSK1002, induced by the chemical mutagens
      furylfuramide, MeIQ, and Trp-P-1.

PMID- 15568780
TI  - (2S,3R)-2-aminododecan-3-ol, a new antifungal agent from the ascidian Clavelina
      oblonga.
AB  - A new antifungal agent, (2S,3R)-2-aminododecan-3-ol (1), has been isolated from
      the ascidian Clavelina oblonga collected in Brazil. The structure of 1 was
      established by analysis of spectroscopic data, including absolute stereochemistry
      determined by circular dichroism analysis of the dibenzoyl derivative 2. Compound
      1 displayed antifungal activity against Candida albicans ATCC 10231 with a MIC of
      0.7 mug/mL and against Candida glabrata with a MIC of 30 microg/mL.

PMID- 15568781
TI  - Indole glucoalkaloids from Chimarrhis turbinata and their evaluation as
      antioxidant agents and acetylcholinesterase inhibitors.
AB  - As part of our study on bioactive agents from Brazilian rainforest plants, two
      new glucoalkaloids, 3,4-dehydro-strictosidine (1) and 3,4-dehydro-strictosidinic
      acid (2), were isolated from Chimarrhis turbinata, along with seven known
      glucoalkaloids, cordifoline (3), strictosidinic acid (4), strictosidine (5), 5
      alpha-carboxystrictosidine (6), turbinatine (7), desoxycordifoline (8), and
      harman-3-carboxylic acid (9). The structures of the new alkaloids were
      established on the basis of comprehensive spectral analysis, mainly 1D and 2D NMR
      experiments, as well as high-resolution HRESIMS. Alkaloid 3 showed strong free
      radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well
      as pronounced antioxidant activity evidenced by redox properties measured by ElCD
      HPLC. Additionally, alkaloids 1-9 were submitted to TLC screening for
      acetylcholinesterase inhibitors. Both 7 and 8 were shown to be moderate
      acetylcholinesterase inhibitors at a concentration of 0.1 and 1.0 microM,
      respectively. In an in vitro rat brain assay, 7 showed moderate activity (IC(50)
      1.86 microM), compared to the standard compound, galanthamine (IC(50) 0.92
      microM).

PMID- 15568782
TI  - Monoterpene indole alkaloids from Palicourea crocea.
AB  - Two new monoterpene indole alkaloids, named croceaines A (1) and B (2), were
      isolated from the leaves of Palicourea crocea. The structures of 1 and 2 were
      elucidated by means of spectroscopic methods.

PMID- 15568783
TI  - New macrolides from the sponge Chondrosia corticata.
AB  - Three new oxazole-containing metabolites, neohalichondramide (5), (19Z)
      halichondramide (6), and secohalichondramide (7), along with four previously
      reported compounds of the same structural class were isolated from the marine
      sponge Chondrosia corticata collected from Guam. The structures of novel
      compounds were determined on the basis of combined spectroscopic analyses. These
      compounds exhibited significant cytotoxicity and antifungal activity toward the
      human leukemia cell-line K562 and Candida albicans, respectively.

PMID- 15568784
TI  - New sesquiterpenes from Capsicum annuum.
AB  - The ethyl acetate soluble fraction of a MeOH extract of the dried stems and roots
      of Capsicum annum gave 10 new sesquiterpenoids (1-10) and nine known compounds.
      The structures of the new compounds were elucidated on the basis of spectroscopic
      evidence. The isolated new compounds were evaluated for their cytotoxic
      activities.

PMID- 15568785
TI  - Petrobactin sulfonate, a new siderophore produced by the marine bacterium
      Marinobacter hydrocarbonoclasticus.
AB  - Culture of the oil-degrading marine bacterium Marinobacter hydrocarbonoclasticus
      gave the known siderophore petrobactin (1) and the new metabolite petrobactin
      sulfonate (2), the first marine siderophore containing a sulfonated 3,4-dihydroxy
      aromatic ring. The structure of petrobactin sulfonate was elucidated from
      spectral data, resulting in a revision of the NMR assignments of petrobactin.

PMID- 15568786
TI  - A new ene-triyne antibiotic from the fungus Baeospora myosura.
AB  - The isolation and structure elucidation of 1 from the Basidomycete fungus
      Baeospora myosura is described. This new ene-triyne antibiotic was most potent
      against Gram-positive bacteria, while it was less active against Gram-negative
      bacteria and a yeast. MICs against several strains of Staphylococcus aureus were
      as low as 0.001 microg/mL. Analogues of 1 that did not contain the ene-triyne
      moiety were inactive against all microorganisms tested. The isolation of this new
      natural product was complicated by the highly reactive nature of the conjugated
      terminal polyacetylene.

PMID- 15568787
TI  - Diterpenoids from the flowers of Rhododendron molle.
AB  - Five new grayanane-type diterpenoids, rhodomolleins IX (1), X (2), XI (3), XII
      (4), and XIII (5), a new kalmane-type diterpenoid, rhodomollein XIV (6), and
      seven known diterpenoids, grayanotoxin II, rhodomolleins I and XIX, rhodojaponins
      II, III, and VI (7), and kalmanol, were isolated from the flowers of Rhododendron
      molle. The structures of 1-6 were elucidated by spectroscopic methods, including
      1D and 2D NMR experiments.

PMID- 15568788
TI  - New briaranes from the South China Sea gorgonian Junceella juncea.
AB  - Three new briarane diterpenes, juncins O-Q (1-3), along with five known
      briaranes, praelolide, junceellin A, gemmacolide A, gemmacolide B, and
      junceellolide D, were isolated from the EtOH/CH(2)Cl(2) extracts of the South
      China Sea gorgonian coral Junceella juncea. The structures of 1-3 were
      established by extensive spectroscopic analysis, including 1D and 2D NMR data.

PMID- 15568789
TI  - Activity-guided fractionation of the leaves of Ormosia sumatrana using a
      proteasome inhibition assay.
AB  - Activity-guided fractionation of a chloroform-soluble extract of the leaves of
      Ormosia sumatrana, using a proteasome inhibition assay, led to the isolation of a
      new A-type proanthocyanidin derivative, 3'-O-cinnamoylprocyanidin A-2 (1), and a
      new cerebroside, sumatranoside (2). The structures of these two isolates were
      determined as epicatechin-(2 beta-->O-->7',4 beta-->8')-epicatechin-3'-O
      cinnamate (1) and 1-O-(beta-d-glucopyranosyl)-(2S,3S,4R)-2N-[(2'R)-2'-hydroxy
      tetracosanoyl]-9Z-octadecene-1,3,4-triol (2), respectively, by spectroscopic and
      chemical methods. Sumatranoside (2) exhibited proteasome inhibitory activity with
      an IC(50) value of 30 microM.

PMID- 15568790
TI  - Two new cytotoxic tetracyclic tetraterpenoids from the soft coral Sarcophyton
      tortuosum.
AB  - Two new cytotoxic tetracyclic tetraterpenoids, methyl tortuoate A (1) and methyl
      tortuoate B (2), along with the known methyl sartortuoate (3) were isolated from
      the soft coral Sarcophyton tortuosum. The structures of 1 and 2 were established
      by spectroscopic methods, mainly on the basis of 2D NMR techniques, and were
      confirmed by single-crystal X-ray diffraction analysis. The cytotoxic activities
      of these compounds were carried out in vitro on human nasophyringeal carcinoma
      (CNE-2) and murine lymphocytic leukemia (P-388) tumor cell lines.

PMID- 15568791
TI  - Chemical constituents from the Colombian medicinal plant Maytenus laevis.
AB  - The methanol extract of the bark of the Colombian medicinal plant Maytenus laevis
      gave six new compounds and 28 known compounds. The structures of the new and
      known compounds were elucidated on the basis of spectroscopic evidence. Several
      of these compounds were screened for cytokine-inducing activity on human PBMCs to
      investigate antitumor effects, and canophyllol (12) demonstrated the most
      effective induction of the cytokines.

PMID- 15568792
TI  - New sesquiterpenes from Pluchea arabica.
AB  - Two new sesquiterpenes, godotol A (1) and godotol B (2), were isolated from
      Pluchea arabica. Their structures were determined by analysis of NMR data. The
      absolute configurations of 1 and 2 were established by Mosher ester methodology.
      The godotols displayed weak activity against bacteria and the brine shrimp
      larvae. They were also inactive in the DPPH antioxidant assay.

PMID- 15568793
TI  - Regioselective syntheses of 2,3,4-tribromopyrrole and 2,3,5-tribromopyrrole.
AB  - 2,3,4-Tribromopyrrole (1) and 2,3,5-tribromopyrrole (2) were each synthesized
      from pyrrole. Spectral data and antifeedant effects for synthetic 1 and the
      antipredatory chemical defense compound of the marine hemichordate Saccoglossus
      kowalevskii were in agreement, confirming the structure of the deterrent natural
      product as 1. Spectral data for 2 differed from synthetic and natural 1.

PMID- 15568794
TI  - Asmarines I, J, and K and nosyberkol: four new compounds from the marine sponge
      Raspailia sp.
AB  - Five asmarines, the known A and F and three new ones, I, J, and K, and four
      diterpenes, the known chelodane, barekoxide, and zaatirin and a new one,
      nosyberkol, were isolated from the Nosy Be Islands (Madagascar) sponge Raspailia
      sp. The structures of all these compounds were established on the basis of MS and
      NMR data. A biogenesis for the various Raspailia sp. diterpenes is suggested.

PMID- 15568795
TI  - Antibacterial activity of naphthoquinones and triterpenoids from Euclea
      natalensis root bark.
AB  - Phytochemical studies of an ethanolic extract of Euclea natalensis root bark
      afforded two new compounds, octahydroeuclein (1) and 20(29)-lupene-3 beta
      isoferulate (2), in addition to three known compounds, shinanolone (3), lupeol,
      and betulin. The chemical structures of 1 and 2 were determined by spectroscopic
      means. Shinanolone (3) showed inhibitory activity against Gram-positive bacterial
      strains and a drug-sensitive strain of Mycobacterium tuberculosis at a
      concentration of 0.1 mg/mL.

PMID- 15568796
TI  - Structure confirmation of a bioactive lactone isolated from Otoba parvifolia
      through the synthesis of a model compound.
AB  - Synthesis of a model compound 4 structurally related to a bioactive lactone 3
      isolated from Otoba parvifolia has been accomplished. The good match between the
      NMR data of both compounds suggests they have identical bicyclic [3.3.1] carbon
      skeletons.

PMID- 15568797
TI  - Annoglabayin, a novel dimeric kaurane diterpenoid, and apoptosis in Hep G2 cells
      of annomontacin from the fruits of Annona glabra.
AB  - Annoglabayin (1), a novel Annona dimeric kaurane diterpenoid, has been isolated
      from Annona glabra, and its structure was determined on the basis of
      spectroscopic analysis. Annoglabayin (1) contains a unique carbon bridge between
      two nor-ent-kaurane monomeric units. The dose-response of 2 in Hep G2 cells
      indicated that 2 increased DNA damage. In addition, our results showed that 2
      induced a noticeable decrease in mitochondrial transmembrane potential during
      treatment. These results indicate that 2 produces apoptotic events in Hep G2
      cells, through inducing changes in mitochondria.

PMID- 15568798
TI  - Furanolabdane diterpenes from Hypoestes purpurea.
AB  - Four new furanolabdane diterpenes, hypopurin A (1), hypopurin B (2), hypopurin C
      (3), and hypopurin D (4), together with eight lignans, alpha-O-methylcubebin,
      beta-O-methylcubebin, hinoquinin, helioxanthin, 7-hydroxyhinokinin,
      dehydroxycubebin, justicidine E, and (-)-hibalactone, as well as two triterpenes,
      lupeol and betulin, were isolated from the dried aerial part of Hypoestes
      purpurea. The structures of 1-4 were elucidated mainly on the basis of NMR and
      MS. Compound 1 was found to be moderately cytotoxic toward the KB cell line with
      an IC(50) value of 9.4 microM.

PMID- 15568799
TI  - Psychrophilin B and C: cyclic nitropeptides from the psychrotolerant fungus
      Penicillium rivulum.
AB  - Psychrophilins B (1) and C (2), two new cyclic nitropeptides, have been isolated
      from the psychrotolerant, new species Penicillium rivulum Frisvad. The
      nitropeptides were isolated by high-speed countercurrent chromatography (HSCCC)
      and HPLC using UV-guided fractionation of the organic extract.

PMID- 15568800
TI  - 10-membered macrolides from the insect pathogenic fungus Cordyceps militaris BCC
      2816.
AB  - Three new 10-membered macrolides (1-3) have been isolated from the
      entomopathogenic fungus Cordyceps militaris BCC 2816, together with six known
      compounds, cepharosporolides C (4), E (5), and F (6), 2-carboxymethyl-4-(3'
      hydroxybutyl)furan (7), cordycepin (8), and pyridine-2,6-dicarboxylic acid. The
      structures were determined by analysis of NMR data, and an X-ray analysis was
      performed to confirm the structure of 1. The antimalarial activity of 1-4 and 8
      against Plasmodium falciparum K1 was evaluated.

PMID- 15568802
TI  - Analysis of the role of intraprotein electron transfer in photoreactivation by
      DNA photolyase in vivo.
AB  - Escherichia coli DNA photolyase contains FADH(-) as the catalytic cofactor. The
      cofactor becomes oxidized to the FADH(*) blue neutral radical during
      purification. The E-FADH(*) form of the enzyme is catalytically inert but can be
      converted to the active E-FADH(-) form by a photoreduction reaction that involves
      intraprotein electron transfer from Trp306. It is thought that the E-FADH(*) form
      is also transiently generated during pyrimidine dimer repair by photoinduced
      electron transfer, and it has been suggested that the FADH(*) that is generated
      after each round of catalysis must be photoreduced before the enzyme can engage
      in subsequent rounds of repair. In this study, we introduced the Trp306Phe
      mutation into the chromosomal gene and tested the non-photoreducible W306F mutant
      for photorepair in vivo. We find that both wild-type and W306F mutant photolyases
      carry out at least 25 rounds of photorepair at the same rate. We conclude that
      photoreduction by intraprotein electron transfer is not part of the photolyase
      photocycle under physiological conditions.

PMID- 15568803
TI  - Role of neighboring FMN side chains in the modulation of flavin reduction
      potentials and in the energetics of the FMN:apoprotein interaction in Anabaena
      flavodoxin.
AB  - Flavodoxins (Flds) are electron transfer proteins that carry a noncovalently
      bound flavin mononucleotide molecule (FMN) as a redox active center. A
      distinguishing feature of these flavoproteins is the dramatic change in the
      E(sq/rd) reduction potential of the FMN upon binding to the apoprotein (at pH
      8.0, from -269 mV when free in solution to -438 mV in Anabaena Fld). In this
      study, the contribution of three neighboring FMN residues, Thr56, Asn58, and
      Asn97, and of three negatively charged surface residues, Glu20, Asp65, and Asp96,
      to modulate the redox properties of FMN upon its binding to the apoprotein has
      been investigated. Additionally, the role of these residues in the
      apoflavodoxin:FMN interaction has been analyzed. Concerning the redox potentials,
      the most noticeable result was obtained for the Thr56Gly mutant. In this Fld
      variant, the increased accessibility of FMN leads to an increase of +63 mV in the
      E(sq/rd) value. On the other hand, a correlation between the electrostatic
      environment of FMN and the E(sq/rd) has been observed. The more positive residues
      or the less negative residues present in the surroundings of the FMN N(1) atom,
      then the less negative the value for E(sq/rd). With regard to FMN binding to
      apoflavodoxin, breaking of hydrophobic interactions between FMN and residues 56,
      58, and 97 seems to increase the K(d) values, especially in the Thr56Gly Fld.
      Such results suggest that the H-bond network in the FMN environment influences
      the FMN affinity.

PMID- 15568804
TI  - Role of S'1 loop residues in the substrate specificities of pepsin A and
      chymosin.
AB  - Proteolytic specificities of human pepsin A and monkey chymosin were investigated
      with a variety of oligopeptides as substrates. Human pepsin A had a strict
      preference for hydrophobic/aromatic residues at P'1, while monkey chymosin showed
      a diversified preferences accommodating charged residues as well as
      hydrophobic/aromatic ones. A comparison of residues forming the S'1 subsite
      between mammalian pepsins A and chymosins demonstrated the presence of
      conservative residues including Tyr(189), Ile(213), and Ile(300) and group
      specific residues in the 289-299 loop region near the C terminus. The group
      specific residues consisted of hydrophobic residues in pepsin A (Met(289),
      Leu/Ile/Val(291), and Leu(298)) and charged or polar residues in chymosins
      (Asp/Glu(289) and Gln/His/Lys(298)). Because the residues in the loop appeared to
      be involved in the unique specificities of respective types of enzymes, site
      directed mutagenesis was undertaken to replace pepsin-A-specific residues by
      chymosin-specific ones and vice versa. A yeast expression vector for glutathione
      S-transferase fusion protein was newly developed for expression of mutant
      proteins. The specificities of pepsin-A mutants could be successfully altered to
      the chymosin-like preference and those of chymosin mutants, to pepsin-like
      specificities, confirming residues in the S'1 loop to be essential for unique
      proteolytic properties of the enzymes. An increase in preference for charged
      residues at P'1 in pepsin-A mutants might have been due to an increase in the
      hydrogen-bonding interactions. In chymosin mutants, the reverse is possible. The
      changes in the catalytic efficiency for peptides having charged residues at P'1
      were dominated by k(cat) rather than K(m) values.

PMID- 15568805
TI  - Solution structure and backbone dynamics of the N-terminal region of the calcium
      regulatory domain from soybean calcium-dependent protein kinase alpha.
AB  - Ca(2+)-dependent protein kinases (CDPKs) are vital Ca(2+)-signaling proteins in
      plants and protists which have both a kinase domain and a self-contained calcium
      regulatory calmodulin-like domain (CLD). Despite being very similar to CaM (>40%
      identity) and sharing the same fold, recent biochemical and structural evidence
      suggests that the behavior of CLD is distinct from its namesake, calmodulin. In
      this study, NMR spectroscopy is employed to examine the structure and backbone
      dynamics of a 168 amino acid Ca(2+)-saturated construct of the CLD (NtH-CLD) in
      which almost the entire C-terminal domain is exchange broadened and not visible
      in the NMR spectra. Structural characterization of the N-terminal domain
      indicates that the first Ca(2+)-binding loop is significantly more open than in a
      recently reported structure of the CLD complexed with a putative intramolecular
      binding region (JD) in the CDPK. Backbone dynamics suggest that parts of the
      third helix exhibit unusually high mobility, and significant exchange, consistent
      with previous findings that this helix interacts with the C-terminal domain.
      Dynamics data also show that the "tether" region, consisting of the first 11
      amino acids of CLD, is highly mobile and these residues exhibit distinctive beta
      type secondary structure, which may help to position the JD and CLD. Finally, the
      unusual global dynamic behavior of the protein is rationalized on the basis of
      possible interdomain rearrangements and the highly variable environments of the C
      and N-terminal domains.

PMID- 15568806
TI  - Single-turnover kinetics of homoprotocatechuate 2,3-dioxygenase.
AB  - Homoprotocatechuate 2,3-dioxygenase isolated from Brevibacterium fuscum utilizes
      an active site Fe(II) and O(2) to catalyze proximal extradiol cleavage of the
      substrate aromatic ring. In contrast to other members of the ring cleaving
      dioxygenase family, the transient kinetics of the extradiol dioxygenase catalytic
      cycle have been difficult to study because the iron is nearly colorless and EPR
      silent. Here, it is shown that the reaction cycle kinetics can be monitored by
      utilizing the alternative substrate 4-nitrocatechol (4NC), which is also cleaved
      in the proximal extradiol position. Changes in the optical spectrum of 4NC
      occurring as a result of ionization, environmental changes, and ring cleavage
      allow both the substrate binding and product formation phases of the reaction to
      be studied. It is shown that substrate binding occurs in a four-step process
      probably involving binding to two ionization states of the enzyme at different
      rates. Following an initial rapid binding of the monoanionic 4NC in the active
      site, slower binding to the Fe(II) and conversion to the dianionic form occur.
      The bound dianionic 4NC reacts rapidly with O(2) in four additional steps,
      apparently occurring in sequence. On the basis of the optical properties of the
      intermediates, these steps are hypothesized to be O(2) binding to the iron,
      isomerization of the resulting complex, ring opening, and product release. The
      natural substrate appears to form the same intermediates but with much larger
      rate constants. These are the first transient intermediates to be reported for an
      extradiol dioxygenase reaction.

PMID- 15568807
TI  - High-resolution X-ray structure of the unexpectedly stable dimer of the [Lys(-2)
      Arg(-1)-des(17-21)]endothelin-1 peptide.
AB  - Previous structural studies on the [Lys((-2))-Arg((-1))]endothelin-1 peptide (KR
      ET-1), 540-fold less potent than ET-1, strongly suggested the presence of an
      intramolecular Arg(-1)-Asp(8) (R(-1)-D(8)) salt bridge that was also observed in
      the shorter [Lys((-2))-Arg((-1))-des(17-21)]endothelin-1 derivative (KR-CSH-ET).
      In addition, for these two analogues, we have shown that the Lys-Arg dipeptide,
      which belongs to the prosequence, significantly improves the formation of the
      native disulfide bonds (>or=96% instead of approximately 70% for ET-1). In
      contrast to what was inferred from NMR data, molecular dynamics simulations
      suggested that such an intramolecular salt bridge would be unstable. The KR-CSH
      ET peptide has now been crystallized at pH 5.0 and its high-resolution structure
      determined ab initio at 1.13 A using direct methods. Unexpectedly, KR-CSH-ET was
      shown to be a head-to-tail symmetric dimer, and the overall interface involves
      two intermolecular R(-1)-D(8) salt bridges, a two-stranded antiparallel beta
      sheet, and hydrophobic contacts. Molecular dynamics simulations carried out on
      this dimer clearly showed that the two intermolecular salt bridges were in this
      case very stable. Sedimentation equilibrium experiments unambiguously confirmed
      that KR-ET-1 and KR-CSH-ET also exist as dimers in solution at pH 5.0. On the
      basis of the new dimeric structure, previous NMR data were reinterpreted.
      Structure calculations were performed using 484 intramolecular and 38
      intermolecular NMR-derived constraints. The solution and the X-ray structures of
      the dimer are very similar (mean rmsd of 0.85 A). Since the KR dipeptide at the N
      terminus of KR-CSH-ET is present in the prosequence, it can be hypothesized that
      similar intermolecular salt bridges could be involved in the in vivo formation of
      the native disulfide bonds of ET-1. Therefore, it appears to be likely that the
      prosequence does assist the ET-1 folding in a chaperone-like manner before
      successive cleavages that yield the bioactive ET-1 hormone.

PMID- 15568808
TI  - Targeting DNA with novel diphenylcarbazoles.
AB  - Double-stranded DNA is a therapeutic target for a variety of anticancer and
      antimicrobial drugs. Noncovalent interactions of small molecules with DNA usually
      occur via intercalation of planar compounds between adjacent base pairs or minor
      groove recognition by extended crescent-shaped ligands. However, the dynamic and
      flexibility of the DNA platform provide a variety of conformations that can be
      targeted by structurally diverse compounds. Here, we propose a novel DNA-binding
      template for construction of new therapeutic candidates. Four bisphenylcarbazole
      derivatives, derived from the combined molecular architectures of known antitumor
      bisphenylbenzimidazoles and anti-infectious dicationic carbazoles, have been
      designed, and their interaction with DNA has been studied by a combination of
      biochemical and biophysical methods. The substitutions of the bisphenylcarbazole
      core with two terminal dimethylaminoalkoxy side chains strongly promote the
      interaction with DNA, to prevent the heat denaturation of the double helix. The
      deletion or the replacement of the dimethylamino-terminal groups with hydroxyl
      groups strongly decreased DNA interaction, and the addition of a third cationic
      side chain on the carbazole nitrogen reinforced the affinity of the compound for
      DNA. Although the bi- and tridentate molecules both derive from well
      characterized DNA minor-groove binders, the analysis of their binding mode by
      means of circular and linear dichroism methods suggests that these compounds form
      intercalation complexes with DNA. Negative-reduced dichroism signals were
      recorded in the presence of natural DNA and synthetic AT and GC polynucleotides.
      The intercalation hypothesis was validated by unwinding experiments using
      topoisomerase I. Prominent gel shifts were observed with the di- and
      trisubstituted bisphenylcarbazoles but not with the uncharged analogues. These
      observations, together with the documented stacking properties of such molecules
      (components for liquid crystals), prompted us to investigate their binding to the
      human telomeric DNA sequence by means of biosensor surface plasmon resonance.
      Under conditions favorable to G4 formation, the title compounds showed only a
      modest interaction with the telomeric quadruplex sequence, comparable to that
      measured with a double-stranded oligonucleotide. Their sequence preference was
      explored by DNase I footprinting experiments from which we identified a composite
      set of binding sequences comprising short AT stretches and a few other mixed
      AT/GC blocks with no special AT character. The variety of the binding sequences
      possibly reflects the coexistence of distinct positioning of the chromophore in
      the intercalation sites. The bisphenylcarbazole unit represents an original
      pharmacophore for DNA recognition. Its branched structure, with two or three arms
      suitable to introduce a structural diversity, provides an interesting scaffold to
      built molecules susceptible to discriminate between the different conformations
      of nucleic acids.

PMID- 15568809
TI  - Structural basis for the self-chaperoning function of an RNA collapsed state.
AB  - Prior to folding to a native functional structure, many large RNAs form
      conformationally collapsed states. Formation of the near-native collapsed state
      for the bI5 group I intron RNA plays an obligatory role in self-chaperoning
      assembly with its CBP2 protein cofactor by preventing formation of stable,
      misassembled complexes. We show that the collapsed state is essential because
      CBP2 assembles indiscriminately with the bI5 RNA in any folding state to form
      long-lived complexes. The most stable protein interaction site in the expanded
      state-CBP2 complex overlaps, but is not identical to, the native site. Folding to
      the collapsed state circumvents two distinct misassembly events: inhibitory
      binding by multiple equivalents of CBP2 and formation of bridged complexes in
      which CBP2 straddles cognate and noncognate RNAs. Strikingly, protein-bound sites
      in the expanded state RNA complex are almost the inverse of native RNA-RNA and
      RNA-protein interactions, indicating that folding to the collapsed state
      significantly reduces the fraction of RNA surfaces accessible for misassembly.
      The self-chaperoning function for the bI5 collapsed state is likely to be
      conserved in other ribonucleoproteins where a protein cofactor binds tightly at a
      simple RNA substructure or has an RNA binding surface composed of multiple
      functional sites.

PMID- 15568810
TI  - NMR structures of the C-terminal segment of surfactant protein B in detergent
      micelles and hexafluoro-2-propanol.
AB  - Although the membrane-associated surfactant protein B (SP-B) is an essential
      component of lung surfactant, which is itself essential for life, the molecular
      basis for its activity is not understood. SP-B's biophysical functions can be
      partially mimicked by subfragments of the protein, including the C-terminus. We
      have used NMR to determine the structure of a C-terminal fragment of human SP-B
      that includes residues 63-78. Structure determination was performed both in the
      fluorinated alcohol hexafluoro-2-propanol (HFIP) and in sodium dodecyl sulfate
      (SDS) micelles. In both solvents, residues 68-78 take on an amphipathic helical
      structure, in agreement with predictions made by comparison to homologous saposin
      family proteins. In HFIP, the five N-terminal residues of the peptide are largely
      unstructured, while in SDS micelles, these residues take on a well-defined
      compact conformation. Differences in helical residue side chain positioning
      between the two solvents were also found, with better agreement between the
      structures for the hydrophobic face than the hydrophilic face. A paramagnetic
      probe was used to investigate the position of the peptide within the SDS micelles
      and indicated that the peptide is located at the water interface with the
      hydrophobic face of the helix oriented inward, the hydrophilic face of the helix
      oriented outward, and the N-terminal residues even farther from the micelle
      center than those on the hydrophilic face of the alpha-helix. Interactions of
      basic residues of SP-B with anionic lipid headgroups are known to have an impact
      on function, and these studies demonstrate structural ramifications of such
      interactions via the differences observed between the peptide structures
      determined in HFIP and SDS.

PMID- 15568811
TI  - New water-soluble phosphines as reductants of peptide and protein disulfide
      bonds: reactivity and membrane permeability.
AB  - Tris(2-carboxyethyl)phosphine (TCEP) is a widely used substitute for
      dithiothreitol (DTT) in the reduction of disulfide bonds in biochemical systems.
      Although TCEP has been recently shown to be a substrate of the flavin-dependent
      sulfhydryl oxidases, there is little quantitative information concerning the rate
      by which TCEP reduces other peptidic disulfide bonds. In this study, mono-, di-,
      and trimethyl ester analogues of TCEP were synthesized to evaluate the role of
      carboxylate anions in the reduction mechanism, and to expand the range of
      phosphine reductants. The effectiveness of all four phosphines relative to DTT
      has been determined using model disulfides, including a fluorescent disulfide
      containing peptide (H(3)N(+)-VTWCGACKM-NH(2)), and with protein disulfide bonds
      in thioredoxin and sulfhydryl oxidase. Mono-, di-, and trimethyl esters exhibit
      phosphorus pK values of 6.8, 5.8, and 4.7, respectively, extending their
      reactivity with the model peptide to correspondingly lower pH values relative to
      that of TCEP (pK = 7.6). At pH 5.0, the order of reactivity is as follows:
      trimethyl- > dimethyl- > monomethyl- > TCEP >> DTT; tmTCEP is 35-fold more
      reactive than TCEP, and DTT is essentially unreactive. Esterification also
      increases lipophilicity, allowing tmTCEP to penetrate phospholipid bilayers
      rapidly (>30-fold faster than DTT), whereas the parent TCEP is impermeant.
      Although more reactive than DTT toward small-molecule disulfides at pH 7.5, all
      phosphines are markedly less reactive toward protein disulfides at this pH.
      Molecular modeling suggests that the nucleophilic phosphorus of TCEP is more
      sterically crowded than the thiolate of DTT, contributing to the lower reactivity
      of the phosphine with protein disulfides. In sum, these data suggest that there
      is considerable scope for the synthesis of phosphine analogues tailored for
      specific applications in biological systems.

PMID- 15568812
TI  - Twisting of the second transmembrane alpha-helix of the mitochondrial ADP/ATP
      carrier during the transition between two carrier conformational states.
AB  - To investigate the structural and functional features of the second alpha-helical
      transmembrane segment (TM2) of the mitochondrial ADP/ATP carrier (AAC), we
      adopted cysteine scanning mutagenesis analysis. Single-cysteine mutations of
      yeast AAC were systematically introduced at residues 98-106 in TM2, and the
      mutants were treated with the fluorescent SH reagent eosin-5-maleimide (EMA). EMA
      modified different amino acid residues of alpha-helical TM2 between the two
      distinct carrier conformations, called the m-state and the c-state, in which the
      substrate recognition site faces the matrix and cytosol, respectively. When amino
      acids in the helix were projected on a wheel plot, these EMA-modified amino acids
      were observed at distinct sides of the wheel. Since the SH reagent specifically
      modified cysteine in the water-accessible environment, these results indicate
      that distinct helical surfaces of TM2 faced the water-accessible space between
      the two conformations, possibly as a result of twisting of this helix. In the
      recently reported crystal structure of bovine AAC, several amino acids faced
      cocrystallized carboxyatractyloside (CATR), a specific inhibitor of the carrier.
      These residues correspond to those modified with EMA in the yeast carrier in the
      c-state. Since the binding site of CATR is known to overlap that of the transport
      substrate, the water-accessible space was thought to be a substrate transport
      pathway, and hence, the observed twisting of TM2 between the m-state and the c
      state may be involved in the process of substrate translocation. On the basis of
      the results, the roles of TM2 in the transport function of AAC were discussed.

PMID- 15568813
TI  - Alpha-anomeric deoxynucleotides, anoxic products of ionizing radiation, are
      substrates for the endonuclease IV-type AP endonucleases.
AB  - Alpha-anomeric 2'-deoxynucleosides (alphadN) are one of the products formed by
      ionizing radiation (IR) in DNA under anoxic conditions. Alpha-2'-deoxyadenosine
      (alphadA) and alpha-thymidine (alphaT) are not recognized by DNA glycosylases,
      and are likely removed by the alternative nucleotide incision repair (NIR)
      pathway. Indeed, it has been shown that alphadA is a substrate for the
      Escherichia coli Nfo and human Ape1 proteins. However, the repair pathway for
      removal of alphadA and other alphadN in yeast is unknown. Here we report that
      alphadA when present in DNA is recognized by the Saccharomyces cerevisiae Apn1
      protein, a homologue of Nfo. Furthermore, alphaT is a substrate for Nfo and Apn1.
      Kinetic constants indicate that alphadA and alphaT are equally good substrates,
      as a tetrahydrofuranyl (THF) residue, for Nfo and Apn1. Using E. coli and S.
      cerevisiae cell-free extracts, we have further substantiated the role of the nfo
      and apn1 gene products in the repair of alphadN. Surprisingly, we found that
      bacteria and yeast NIR-deficient mutants are not sensitive to IR, suggesting that
      DNA strand breaks with terminal 3'-blocking groups rather than alphadN might
      contribute to cell survival. We propose that the novel substrate specificities of
      Nfo and Apn1 play an important role in counteracting oxidative DNA base damage.

PMID- 15568814
TI  - In vitro replication and repair of DNA containing a C2'-oxidized abasic site.
AB  - Abasic lesions are unable to form Watson-Crick hydrogen bonds with nucleotides.
      Nonetheless, polymerase and repair enzymes distinguish between various oxidized
      abasic lesions, as well as from nonoxidized abasic sites (AP). The C2-AP lesion
      is produced when DNA is exposed to gamma-radiolysis. Its effects on polymerases
      and repair enzymes are unknown. A recently reported method for the chemical
      synthesis of oligonucleotides containing C2-AP at a defined site was utilized for
      studying the activity of Klenow exo(-) and repair enzymes on templates containing
      the lesion. The C2-AP lesion has a similar effect on Klenow exo(-) as do AP and
      C4-AP sites. Deoxyadenosine is preferentially incorporated opposite C2-AP, but
      extension of the primer past the lesion is strongly blocked. C2-AP is incised
      less efficiently by exonuclease III and endonuclease IV than are other abasic
      lesions. Furthermore, although a Schiff base between C2-AP and endonuclease III
      can be chemically trapped, the location of the 3'-phosphate alpha with respect to
      the aldehyde prevents beta-elimination associated with the lyase activity of type
      I base excision repair enzymes. The interactions of the C2'-oxidized abasic site
      with Klenow exo(-) and repair enzymes suggest that the lesion will be mutagenic
      and that it will be removed by strand displacement synthesis and flap
      endonuclease processing via a long patch repair mechanism.

PMID- 15568815
TI  - Transcription-dependent polyubiquitination of RNA polymerase II requires lysine
      63 of ubiquitin.
AB  - Lysine-63-linked polyubiquitin chains are not thought to signal protein
      degradation but instead signal for a variety of cellular processes including some
      types of DNA repair. RNA polymerase (Pol) II is polyubiquitinated following DNA
      damage or upon treatment of nuclear extracts with the transcription inhibitor
      alpha-amanitin. Here, we report, using a reaction in vitro, that transcription
      dependent polyubiquitination of RNA Pol II consists of lysine-63-linked chains.
      This modification is specific for RNA Pol II engaged in active transcription and
      arrested by alpha-amanitin.

PMID- 15568816
TI  - Proton donor in yeast pyruvate kinase: chemical and kinetic properties of the
      active site Thr 298 to Cys mutant.
AB  - The active site T298 residue of yeast pyruvate kinase (YPK), located in a
      position to serve potentially as the proton donor, was mutated to cysteine. T298C
      YPK was isolated and purified, and its enzymatic properties were characterized.
      Fluorescence and CD spectra indicate minor structural perturbations. A kinetic
      analysis of the Mg(2+)-activated enzyme demonstrates no catalytic activity in the
      absence of the heterotropic activator fructose 1,6-bisphosphate (FBP). In the
      presence of Mg(2+) and FBP, T298C has approximately 20% of the activity of wild
      type (wt) YPK. The activator constant for FBP increases by 1 order of magnitude
      compared to this constant with the wt enzyme. T298C shows positive cooperativity
      by FBP with a Hill coefficient of 2.6 (wt, n(H,FBP) = 1). Mn(2+)-activated T298C
      behaves like Mn(2+)-activated wt YPK with a V(max) that is 20% of that for the wt
      enzyme with or without FBP. A pH-rate profile of T298C relative to that for wt
      YPK shows that pK(a,2) has shifted from 6.4 in wt to 5.5, indicating that the
      thiol group elicits an acidic pK shift. Inactivation of both wt and T298C by
      iodoacetate elicits a pseudo-first-order loss of activity with T298C being
      inactivated from 8 to 100 times faster than wt YPK. A pH dependence of the
      inactivation rate constant for T298C gives a value of 8.2, consistent with the pK
      for a thiol. Changes in fluorescence indicate that the T298C-Mg(2+) complex binds
      PEP, ADP, and both ligands together. This demonstrates that the lack of activity
      is not due to the loss of substrate binding but to the lack of ability to induce
      the proper conformational change. The mutation also induces changes in binding of
      FBP to all the relevant complexes. Binding of the metal and binding of PEP to the
      enzyme complexes are also differentially altered. Solvent isotope effects are
      observed for both wt and T298C. Proton inventory studies indicate that k(cat) is
      affected by a proton from water in the transition state and the effects are metal
      ion-dependent. The results are consistent with water being the active site proton
      donor. Active site residue T298 is not critical for activity but plays a role in
      the activation of the water and affects the pK that modulates catalytic activity.

PMID- 15568817
TI  - Oxygen reactions in p-hydroxybenzoate hydroxylase utilize the H-bond network
      during catalysis.
AB  - para-Hydroxybenzoate hydroxylase is a flavoprotein monooxygenase that catalyses a
      reaction in two parts: reduction of the flavin adenine dinucleotide (FAD) in the
      enzyme by reduced nicotinamide adenine dinucleotide phosphate (NADPH) in response
      to binding p-hydroxybenzoate to the enzyme and oxidation of reduced FAD with
      oxygen to form a hydroperoxide, which then oxygenates p-hydroxybenzoate. These
      different reactions are coordinated through conformational rearrangements of the
      protein and isoalloxazine ring during catalysis. Earlier research showed that
      reduction of FAD occurs when the isoalloxazine of the FAD moves to the surface of
      the protein to allow hydride transfer from NADPH. This move is coordinated with
      protein rearrangements that are triggered by deprotonation of buried p
      hydroxybenzoate through a H-bond network that leads to the surface of the
      protein. In this paper, we examine the involvement of this same H-bond network in
      the oxygen reactions-the initial formation of a flavin-C4a-hydroperoxide from the
      reaction between oxygen and reduced flavin, the electrophilic attack of the
      hydroperoxide upon the substrate to form product, and the elimination of water
      from the flavin-C4a-hydroxide to form oxidized enzyme in association with product
      release. These reactions were measured through absorbance and fluorescence
      changes in the FAD during the reactions. Results were collected over a range of
      pH for the reactions of wild-type enzyme and a series of mutant enzymes with the
      natural substrate and substrate analogues. We discovered that the rate of
      formation of the flavin hydroperoxide is not influenced by pH change, which
      indicates that the proton required for this reaction does not come from the H
      bond network. The rate of the hydroxylation reaction increases with pH in a
      manner consistent with a pK(a) of 7.1. We conclude that the H-bond network
      abstracts the phenolic proton from p-hydroxybenzoate in the transition state of
      oxygen transfer. The rate of formation of oxidized enzyme increases with pH in a
      manner consistent with a pK(a) of 7.1, indicating the involvement of the H-bond
      network. We conclude that product deprotonation enhances the rate of a specific
      conformational change required for both product release and the elimination of
      water from C4a-OH-FAD.

PMID- 15568818
TI  - Mechanism of inhibition of human KSP by monastrol: insights from kinetic analysis
      and the effect of ionic strength on KSP inhibition.
AB  - Kinesin motor proteins utilize the energy from ATP hydrolysis to transport
      cellular cargo along microtubules. Kinesins that play essential roles in the
      mechanics of mitosis are attractive targets for novel antimitotic cancer
      therapies. Monastrol, a cell-permeable inhibitor that specifically inhibits the
      kinesin Eg5, the Xenopus laevis homologue of human KSP, can cause mitotic arrest
      and monopolar spindle formation. In this study, we show that the extent of
      monastrol inhibition of KSP microtubule-stimulated ATP hydrolysis is highly
      dependent upon ionic strength. Detailed kinetic analysis of KSP inhibition by
      monastrol in the presence and absence of microtubules suggests that monastrol
      binds to the KSP-ADP complex, forming a KSP-ADP-monastrol ternary complex, which
      cannot bind to microtubules productively and cannot undergo further ATP-driven
      conformational changes.

PMID- 15568819
TI  - In vitro biosynthesis of glycosylphosphatidylinositol in Aspergillus fumigatus.
AB  - Glycosylphosphatidylinositol (GPI) represents a mechanism for the attachment of
      proteins to the plasma membrane found in all eukaryotic cells. GPI biosynthesis
      has been mainly studied in parasites, yeast, and mammalian cells. Aspergillus
      fumigatus, a filamentous fungus, produces GPI-anchored molecules, some of them
      being essential in the construction of the cell wall. An in vitro assay was used
      to study the GPI biosynthesis in the mycelium form of this organism. In the
      presence of UDP-GlcNAc and coenzyme A, the cell-free system produces the initial
      intermediates of the GPI biosynthesis: GlcNAc-PI, GlcN-PI, and GlcN-(acyl)PI.
      Using GDP-Man, two types of mannosylation are observed. First, one or two mannose
      residues are added to GlcN-PI. This mannosylation, never described in fungi, does
      not require dolichol phosphomannoside (Dol-P-Man) as the monosaccharide donor.
      Second, one to five mannose residues are added to GlcN-(acyl)PI using Dol-P-Man
      as the mannose donor. The addition of ethanolamine phosphate groups to the first,
      second, and third mannose residue is also observed. This latter series of GPI
      intermediates identified in the A. fumigatus cell-free system indicates that GPI
      biosynthesis in this filamentous fungus is similar to the mammalian or yeast
      systems. Thus, these biochemical data are in agreement with a comparative genome
      analysis that shows that all but 3 of the 21 genes described in the Saccharomyces
      cerevisiae GPI pathways are found in A. fumigatus.

PMID- 15568820
TI  - The Delta 14 mutation of human cardiac troponin T enhances ATPase activity and
      alters the cooperative binding of S1-ADP to regulated actin.
AB  - The complex of tropomyosin and troponin binds to actin and inhibits activation of
      myosin ATPase activity and force production of striated muscles at low free
      Ca(2+) concentrations. Ca(2+) stimulates ATP activity, and at subsaturating actin
      concentrations, the binding of NEM-modified S1 to actin-tropomyosin-troponin
      increases the rate of ATP hydrolysis even further. We show here that the Delta14
      mutation of troponin T, associated with familial hypertrophic cardiomyopathy,
      results in an increase in ATPase rate like that seen with wild-type troponin in
      the presence of NEM-S1. The enhanced ATPase activity was not due to a decreased
      incorporation of mutant troponin T with troponin I and troponin C to form an
      active troponin complex. The activating effect was more prominent with a hybrid
      troponin (skeletal TnI, TnC, and cardiac TnT) than with all cardiac troponin.
      Thus it appears that changes in the troponin-troponin contacts that result from
      mutations or from forming hybrids stabilize a more active state of regulated
      actin. An analysis of the effect of the Delta14 mutation on the equilibrium
      binding of S1-ADP to actin was consistent with stabilization of an active state
      of actin. This change in activation may be important in the development of
      cardiac disease.

PMID- 15568821
TI  - Lanthanide spectroscopic studies of the dinuclear and Mg(II)-dependent PvuII
      restriction endonuclease.
AB  - Type II restriction enzymes are homodimeric systems that bind four to eight base
      pair palindromic recognition sequences of DNA and catalyze metal ion-dependent
      phosphodiester cleavage. While Mg(II) is required for cleavage in these enzymes,
      in some systems Ca(II) promotes avid substrate binding and sequence
      discrimination. These properties make them useful model systems for understanding
      the roles of alkaline earth metal ions in nucleic acid processing. We have
      previously shown that two Ca(II) ions stimulate DNA binding by PvuII endonuclease
      and that the trivalent lanthanide ions Tb(III) and Eu(III) support subnanomolar
      DNA binding in this system. Here we capitalize on this behavior, employing a
      unique combination of luminescence spectroscopy and DNA binding assays to
      characterize Ln(III) binding behavior by this enzyme. Upon excitation of tyrosine
      residues, the emissions of both Tb(III) and Eu(III) are enhanced severalfold.
      This enhancement is reduced by the addition of a large excess of Ca(II),
      indicating that these ions bind in the active site. Poor enhancements and
      affinities in the presence of the active site variant E68A indicate that Glu68 is
      an important Ln(III) ligand, similar to that observed with Ca(II), Mg(II), and
      Mn(II). At low micromolar Eu(III) concentrations in the presence of enzyme (10-20
      microM), Eu(III) excitation (7)F(0) --> (5)D(0) spectra yield one dominant peak
      at 579.2 nm. A second, smaller peak at 579.4 nm is apparent at high Eu(III)
      concentrations (150 microM). Titration data for both Tb(III) and Eu(III) fit well
      to a two-site model featuring a strong site (K(d) = 1-3 microM) and a much weaker
      site (K(d) approximately 100-200 microM). Experiments with the E68A variant
      indicate that the Glu68 side chain is not required for the binding of this second
      Ln(III) equivalent; however, the dramatic increase in DNA binding affinity around
      100 microM Ln(III) for the wild-type enzyme and metal-enhanced substrate affinity
      for E68A are consistent with functional relevance for this weaker site. This
      discrimination of sites should make it possible to use lanthanide substitution
      and lanthanide spectroscopy to probe individual metal ion binding sites, thus
      adding an important tool to the study of restriction enzyme structure and
      function.

PMID- 15568822
TI  - High-level expression of rabbit 15-lipoxygenase induces collapse of the
      mitochondrial pH gradient in cell culture.
AB  - A critical step in the development of mammalian erythroblasts into mature red
      blood cells is the extrusion of the nucleus, followed by intracellular
      degradation of the remaining organelles. It has been hypothesized that the
      breakdown of cellular organelles in rabbit reticulocytes is initiated by 15
      lipoxygenase. In vitro, the purified rabbit reticulocyte 15-lipoxygenase binds
      and permeabilizes organellar membranes, thereby releasing the lumenal contents of
      the organelle. Here, we demonstrate that ectopic expression of 15-lipoxygenase
      leads to the collapse of the mitochondrial pH gradient in nonerythroid cells,
      using a novel reporter of mitochondrial pH, mito-pHluorin. No change in
      mitochondrial pH was observed with a mutant of 15-lipoxygenase that lacks
      enzymatic activity. These data demonstrate that 15-lipoxygenase is capable of
      disrupting the pH gradient maintained by mitochondria in living cells without
      additional factors specific for red blood cell development.

PMID- 15568823
TI  - Template-free chemical route to ultrathin single-crystalline films of CuS and CuO
      employing the liquid-liquid interface.
AB  - Ultrathin films of CuS and CuO have been obtained at the liquid-liquid interface
      by the reaction of copper cupferronate solution in toluene with Na(2)S or NaOH in
      aqueous solution. The films are generally single crystalline and around 40 nm
      thick. The thickness and crystallinity of the films are determined by the
      reactant concentrations and reaction conditions. The films have been
      characterized by electron microscopy and atomic force microscopy besides X-ray
      diffraction. Sonication of the films produces nanocrystals and nanorods which are
      also single crystalline.

PMID- 15568824
TI  - Nanoparticle dispersion on reconstructed carbon nanomeshes.
AB  - A nanoporous template which can be used for the preparation of monodispersed
      metal nanoparticles can have wide-ranging applications in the catalyzed growth of
      single-walled nanotubes, as well as the preparation of energetic, nanostructured
      ferromagnetic particle arrays. Here, we found that a honeycomb-like carbon
      nanomesh with periodically arranged pores of approximately 2-nm dimension could
      be fabricated on the reconstructed 6H-SiC(0001) surface. The carbon nanomesh
      arises from the periodic arrangement of segregated carbon clusters on the 6H-SiC
      surface to form a highly regular, nanoporous film. The carbon nanomesh can be
      dynamically structured to control the periodicity and depth of the pores by
      annealing in a vacuum. We evaporated cobalt on the surface of the nanomesh and
      investigated the diffusion and agglomeration behavior of cobalt clusters using in
      situ scanning tunneling microscopy. It is found that monodispersed Co
      nanoclusters that resist aggregation up to a temperature of 500 degrees C can be
      fabricated on this template.

PMID- 15568825
TI  - Mechanism of the transition between lamellar and gyroid phases formed by a
      diblock copolymer in aqueous solution.
AB  - The mechanism of the transition from a lamellar phase to a gyroid phase in an
      aqueous solution of a diblock copolymer has been studied by time-resolved
      synchrotron small-angle X-ray scattering. The transition occurs via a metastable
      perforated lamellar structure. The perforations initially have liquidlike
      ordering before developing hexagonal packing. The transient phase of irregularly
      perforated layers is revealed by the development of diffuse scattering peaks,
      just below the Bragg peaks of the lamellar structure. The diffuse scattering is
      modeled by Monte Carlo simulations of perforated layers. Following the formation
      of perforations, Bragg peaks characteristic of a hexagonal structure signal an
      ordering into a hexagonal lattice (with the concomitant loss of diffuse
      scattering). Computer simulations based on a dynamic density functional model
      reproduce these features. The hexagonal perforated lamellar phase is rapidly
      replaced by the gyroid phase. The domain spacing of the gyroid phase is larger
      than that of the perforated lamellar structure. The perforated lamellar and
      gyroid phases coexist for a defined period. The reverse transition from gyroid to
      lamellae occurs directly, with no transient or metastable intermediates.

PMID- 15568826
TI  - Laser photophoretic migration with periodic expansion-contraction motion of photo
      absorbing microemulsion droplets in water.
AB  - When the water-in-oil (w/o) microemulsion droplets including the Co(III)
      pyridylazo complex as the photo-absorber were irradiated with a continuous-wave
      Ar(+) ion laser (514.5 nm), we have observed unexpected phenomenon that photo
      absorbing microemulsion droplets in water repeated the expansion and the sudden
      contraction during the laser photophoretic migration. The period of the expansion
      contraction cycle was inversely proportional to both the concentration of the
      complex and the irradiated laser power and was independent of the initial size of
      the droplet. The mechanism of the periodic motion of the droplet was investigated
      by local temperature measurement and Raman microscope spectroscopy. It was
      suggested that the first step was the phase separation of the bicontinuous
      microemulsion droplet into the normal w/o microemulsion outer phase and the
      aqueous inner phase in the droplet, which was caused by the laser-induced
      temperature gradient inside the droplet. Subsequently, an expansion of the inner
      aqueous phase was induced by the percolation of the external water by thermo
      osmosis, which was caused by the laser-induced temperature gradient between the
      inside and the outside of the microemulsion liquid membrane of the droplet. When
      the liquid membrane became thinner to a critical thickness, the inner aqueous
      phase was released and the droplet shrank into the original size. The proposed
      mechanism can give an account of the unique cyclical motion.

PMID- 15568827
TI  - Extraction of zirconium nitrate by TBP in n-octane: influence of cation type on
      third phase formation according to the "sticky spheres" model.
AB  - Small-angle neutron scattering (SANS) data for the tri-n-butyl phosphate (TBP)-n
      octane, HNO(3)-Zr(NO(3))(4) solvent extraction system, obtained under a variety
      of experimental conditions, have been interpreted using the Baxter model for hard
      spheres with surface adhesion. The increase in scattering intensity in the low Q
      range observed when increasing amounts of Zr(NO(3))(4) were extracted into the
      organic phase was interpreted as arising from interactions between small reverse
      micelle-like particles containing two to three TBP molecules. Upon extraction of
      Zr(NO(3))(4), the particles interact through attractive forces between their
      polar cores with a potential energy that exceeds 2 k(B)T. The interparticle
      attraction, under suitable conditions, leads to third phase formation. A linear
      relationship exists between the derivative of the potential energy of attraction
      with respect to the concentration of nitrate ions in the organic phase and the
      ionization potential or the hydration enthalpy of the extracted metal cations.

PMID- 15568828
TI  - Shell-cross-linked vesicles synthesized from block copolymers of Poly(D,L
      lactide) and Poly(N-isopropyl acrylamide) as thermoresponsive nanocontainers.
AB  - A polylactide (D,L-PLA) macroRAFT agent was prepared by utilizing a hydroxyl
      functional trithiocarbonate as a coinitiator for the ring-opening polymerization.
      The length of the resultant polymer was controlled by the concentration of the
      coinitiator leading to the formation of two PLA polymers with M(n) = 12500 g mol(
      )(1) (PDI = 1.46) and M(n) = 20500 g mol(-)(1) (PDI = 1.38) each with omega
      trithiocarbonate functionality. Chain extension of PLA via the RAFT (free
      radical) polymerization of N-isopropyl acrylamide (NIPAAm) resulted in the
      formation of amphiphilic block copolymers with the PNIPAAm block increasing in
      size with conversion. TEM measurements of the aggregates obtained by self
      organization of the block copolymers in aqueous solutions indicated the formation
      of vesicles. The sizes of these aggregates were influenced by the ratio of both
      blocks and the molecular weight of each block. The lower critical solution
      temperature (LCST) of the block copolymer was largely unaffected by the size of
      each block. UV turbidity measurements indicated a higher LCST for the block
      copolymers than for the corresponding PNIPAAm homopolymers. Stabilization of the
      vesicles was attained by a cross-linking chain extension of the PNIPAAm block
      using hexamethylene diacrylate. As the trithiocarbonate group was located between
      the PLA and PNIPAAm blocks, the chain extension resulted in a cross-linked layer
      between the core and corona of the vesicles.

PMID- 15568829
TI  - Deviation from the classical colloid filtration theory in the presence of
      repulsive DLVO interactions.
AB  - A growing body of experimental evidence suggests that the deposition behavior of
      microbial particles (e.g., bacteria and viruses) is inconsistent with the
      classical colloid filtration theory (CFT). Well-controlled laboratory-scale
      column deposition experiments were conducted with uniform model particles and
      collectors to obtain insight into the mechanisms that give rise to the diverging
      deposition behavior of microorganisms. Both the fluid-phase effluent particle
      concentration and the profile of retained particles were systematically measured
      over a broad range of physicochemical conditions. The results indicate that, in
      the presence of repulsive Derjaguin-Landau-Verwey-Overbeek (DLVO) interactions,
      the concurrent existence of both favorable and unfavorable colloidal interactions
      causes significant deviation from the CFT. A dual deposition mode model is
      presented which considers the combined influence of "fast" and "slow" particle
      deposition. This model is shown to adequately describe both the spatial
      distribution of particles in the packed bed and the suspended particle
      concentration at the column effluent.

PMID- 15568830
TI  - Phase diagrams of Wyoming Na-montmorillonite clay. Influence of particle
      anisotropy.
AB  - Natural Na-Wyoming montmorillonite was size fractionated by successive
      centrifugation. Polydisperse particles with average sizes of 400, 290, and 75 nm
      were then obtained. As the structural charge of the particles belonging to three
      fractions (determined by cationic exchange capacity measurements) is the same,
      such a procedure allows studying the effect of particle anisotropy on the
      colloidal phase behavior of swelling clay particles. Osmotic stress experiments
      were carried out at different ionic strengths. The osmotic pressure curves
      display a plateau whose beginning systematically coincides with the sol/gel
      transition determined by oscillatory stress measurements. The concentration
      corresponding to the sol/gel transition increases linearly with particle
      anisotropy, which shows that the sol/gel transition is not directly related to an
      isotropic/nematic transition of individual clay particles. Indeed, a reverse
      evolution should be observed for an I/N transition involving the individual clay
      particles. Still, when observed between crossed polarizer and analyzer, the gel
      samples exhibit permanent birefringent textures, whereas in the "sol" region,
      transient birefringence is observed when the samples are sheared. This suggests
      that interacting clay particles are amenable to generate, at rest and/or under
      shear, large anisotropic particle associations.

PMID- 15568831
TI  - Synthesis and characterization of nano titania powder with high photoactivity for
      gas-phase photo-oxidation of benzene from TiOCl(2) aqueous solution at low
      temperatures.
AB  - Nano rutile, anatase, and bicrystalline (anatase + brookite) titania powders with
      an average crystal size of below 10 nm are prepared from aqueous TiOCl(2)
      solution at low temperatures by adjusting pH values of the starting solution and
      adding different additives. Adding a small amount of octyl phenol poly(ethylene
      oxide) into aqueous TiOCl(2) solution leads to the change of particle
      morphologies of obtained nano titania from needlelike to nano spherical rutile
      crystals. Amorphous-anatase transformation of titania could proceed in liquid
      solid reaction at low temperatures, even at room temperature. A formation
      mechanism of rutile, anatase, and brookite titania was proposed. It is found that
      H(+) or H(3)O(+) plays a catalytic role in the phase transformation from
      amorphous to anatase titania and that the presence of a small amount of SO(4)(2)(
      ) ion is unfavorable to the formation of both rutile and brookite. By carefully
      adjusting preparation conditions, nano pure anatase with higher surface area,
      good crystallinity, and a lower recombination rate of photoexcited electrons and
      holes was obtained. This nano pure anatase showed a very good photocatalytic
      activity for gas-phase photo-oxidation of benzene.

PMID- 15568832
TI  - Preparation of microcapsules containing two-phase core materials.
AB  - Urea-formaldehyde (UF) microcapsules containing two-phase core materials in which
      phthalocyanine blue BGS (beta-CuPc) particles were homodispersed in
      tetrachloroethylene (TCE) were prepared by in situ polymerization. The effects of
      the various process parameters, including the type of surface modifier, the
      viscosity of UF prepolymer, the type of water-soluble surfactant, and the
      concentration of oil-soluble surfactant in the capsule core on the dispersity of
      beta-CuPc particles in TCE and the properties of the capsule wall and the
      adsorption of beta-CuPc particles on the internal surface of capsule wall were
      experimentally investigated. It was shown that using octadecylamine (ODA) to
      modify beta-CuPc particles resulted in a significant increase of the dispersing
      extent (DE) and the electrophoresis velocity of the particles in TCE (about 4 and
      20 times more than that of unmodified). In addition, the optimal reaction
      conditions of the synthesis UF prepolymer were obtained by the orthogonal test.
      On the other hand, as the oil/water interfacial tension of emulsion was big
      enough, the microcapsule formed. The concentration of Span-80 in TCE was no less
      than 0.062 mM; the adsorption of beta-CuPc particles on internal surface of wall
      were restrained. Finally, the microcapsules in which beta-CuPc particles possess
      reversible response to dc electric field were obtained.

PMID- 15568833
TI  - Solvent effects on supramolecular gel-phase materials: two-component dendritic
      gel.
AB  - The self-assembly of diaminododecane with dendritic l-lysine-based peptides to
      form gel-phase materials was investigated in a range of different solvents. The
      degree of structuring was modulated by the solvent employed, an effect which
      induced subtle changes in the mesoscale aggregate morphology and macroscopic
      behavior of the self-assembled state. In this paper a range of different solvent
      parameters are investigated, and it is clearly shown that macroscopic gelation
      can be related to a solvent polar solubility parameter for this system. The
      results also show a dependence on Kamlet-Taft hydrogen bonding parameters, and
      this clearly demonstrates the role of the solvent environment in terms of dendron
      -dendron intermolecular hydrogen bonding and its impact on the supramolecular
      chiral organization of the assembled superstructure.

PMID- 15568834
TI  - Conductometric, surface tension, and kinetic studies in mixed SDS-Tween 20 and
      SDS-SB3-12 micellar solutions.
AB  - Micellization in sodium dodecyl sulfate (SDS)-N-dodecyl-N,N-dimethyl-3-ammonio-1
      propanesulfonate and SDS-polyoxyethylenesorbitan monolaurate binary surfactant
      solutions was studied by means of conductivity and surface tension measurements.
      These studies showed that two types of micellar aggregates are present in the
      mixed micellar solutions. Two reactions were investigated in these micellar
      media, the oxidation of 1-methoxy-4-(methylthio)benzene by IO(4)(-) and the
      spontaneous hydrolysis of phenyl chloroformate. Information on the distribution
      of reagents in the micellar reaction media was obtained through conductivity and
      spectroscopic measurements. Discussion of the kinetic data showed that the redox
      reaction takes place mainly in the aqueous phase of the mixed solutions, whereas
      hydrolysis occurs in the aqueous as well as in the micellar pseudophase.
      Variations in the observed rate constants of the two processes studied are
      gradual within the whole surfactant concentration range investigated, revealing
      little information about the mixed micellar medium.

PMID- 15568835
TI  - Influence of silver nanoparticles on the phase behavior of side-chain liquid
      crystalline polymers.
AB  - The synthetic approach to the new class of mesomorphous nanocomposite polymer
      systems was developed. It is based on the in situ reduction of silver ions in the
      liquid crystalline (LC) polymer matrix leading to the formation of nanoparticles
      with typical sizes in the range of 5-30 nm. The influence of silver nanoparticles
      on the phase state of the LC composites, i.e., type and temperature interval of
      the mesophase, was studied. Regardless of chemical structure of the LC polymer
      matrix, an increase in the metal concentration is accompanied by a decrease of
      clearing temperature due to adsorption of macromolecules on the nanoparticle's
      surface. In the case of an LC copolymer with cyanobiphenyl side mesogenic
      fragments, the complete disruption of mesophase is observed below 2 wt% content
      of silver. This phenomenon is, most likely, a result of chemosorption of terminal
      cyano groups on the nanoparticles with the formation of sigma complexes that
      disturb packing of the mesogenic units.

PMID- 15568836
TI  - Faceted structures in Langmuir monolayers of diethylene glycol mono-n-octadecyl
      ether at the air--water interface.
AB  - We have concurrently studied the surface pressure (pi) versus area (A) isotherms
      and microscopic surface morphological features of Langmuir monolayers of
      diethylene glycol mono-n-octadecyl ether (C18E2) by film balance and Brewster
      angle microscopy (BAM) over a wide range of temperature. At temperatures < or =10
      degrees C, the monolayers exist in the form of condensed phase even just after
      the evaporation of the spreading solvent, suggesting that the melting point of
      the condensed phase is above this temperature. At > or =15 degrees C, the
      monolayers can exist as gas (G), liquid expanded (LE), and liquid condensed (LC)
      phases and undergo a pressure-induced first-order phase transition between LE and
      LC phases showing a sharp cusp point followed by a plateau region in the pi-A
      isotherms. A variety of 2-D structures, depending on the subphase temperature,
      are observed by BAM just after the appearance of the cusp point. It is
      interesting to note here that the domains attain increasingly large and compact
      shape as the subphase temperature increases and finally give faceted structures
      with sharp edges and corners at > or =30 degrees C. The BAM observations were
      coupled with polarization modulation infrared reflection absorption spectroscopy
      (PM-IRRAS) to gain better understanding regarding the conformational order and
      subcell packing of the molecules. The constancy of the methylene stretching modes
      over the studied temperature range suggests that the hydrocarbon chains do not
      undergo any conformational changes upon compression of the monolayer. However,
      the full width at half-maximum (fwhm) values of the asymmetric methylene
      stretching mode (nu(as)(CH(2))) are found to respond differently with changes in
      temperature. It is concluded that even though the trans/gauche ratio of the
      hydrocarbon chains remains virtually constant, the LE-LC phase transition upon
      compression of the monolayer is accompanied by a loss of the rotational freedom
      of the molecules.

PMID- 15568837
TI  - Growth kinetics and morphology of self-assembled monolayers formed by contact
      printing 7-octenyltrichlorosilane and octadecyltrichlorosilane on Si(100) wafers.
AB  - The growth kinetics and morphologies of self-assembled monolayers deposited by
      contact printing 7-octenyltrichlorosilane (OCT) and octadecyltrichlorosilane
      (OTS) on Si(100) were studied by ellipsometry and atomic force microscopy. We
      found that, for both OCT and OTS, full monolayers could be obtained at room
      temperature after printing times of 120-180 s; the printing-based monolayer
      assembly processes follow apparent Langmuir adsorption kinetics, with the
      measured film growth rates increasing both with the ambient humidity and with
      concentration of the ink used to load the stamp. At a dew point of 10 degrees C
      and an ink concentration (in toluene) of 50 mM, the observed film growth rate
      constant is 0.05 s(-)(1). When the printing was carried out at a lower ambient
      humidity (dew points of 1-3 degrees C), the measured rates of assembly were
      approximately a factor of 2 slower. Increasing the deposition temperature from 25
      to 45 degrees C under these conditions increased the film growth rate only
      slightly. The morphology of the films depends on the identity of the ink.
      Uniform, high-coverage films could be obtained readily from the eight-carbon
      chain length adsorbate OCT, provided that the stamp was not overloaded with the
      ink; for high concentrations outside of the optimal range, the surface presented
      significant numbers of adsorbed particles ascribed, in part, to siloxane polymers
      formed by hydrolysis of the ink on the stamp before printing. In marked contrast,
      for the 18-carbon adsorbate OTS, the printed films always consisted of a mixture
      of a uniform monolayer plus adsorbed polysiloxane particles. The different film
      morphologies seen for OCT and OTS are proposed to result from the different
      transfer efficiencies of the organotrichlorosilane relative to polysiloxane
      hydrolysis products formed during the printing process. These transfer
      efficiencies exhibit sensitivities related to the permeation of the
      poly(dimethylsiloxane) (PDMS) stamp by the silane reagents. Short-chain inks such
      as OCT evidently permeate the PDMS stamp more deeply than longer-chain inks such
      as OTS. This difference, and the different diffusion rates of ink vs oligomeric
      silane hydrolysis products, determines the film morphology obtained by contact
      printing. The mass transfer dynamics of the process thus yield surface layers
      derived from varying quantities of siloxane oligomers, which subsequently
      transfer to the substrate along with unhydrolyzed silane adsorbate during the
      printing step. The structural evolution of the contact-printed films so obtained
      is strikingly different from that of SAMs prepared by immersion.

PMID- 15568838
TI  - Effects of potential models on the adsorption of ethane and ethylene on
      graphitized thermal carbon black. Study of two-dimensional critical temperature
      and isosteric heat versus loading.
AB  - Adsorption of ethylene and ethane on graphitized thermal carbon black and in slit
      pores whose walls are composed of graphene layers is studied in detail to
      investigate the packing efficiency, the two-dimensional critical temperature, and
      the variation of the isosteric heat of adsorption with loading and temperature.
      Here we used a Monte Carlo simulation method with a grand canonical Monte Carlo
      ensemble. A number of two-center Lennard-Jones (LJ) potential models are
      investigated to study the impact of the choice of potential models in the
      description of adsorption behavior. We chose two 2C-LJ potential models in our
      investigation of the (i) UA-TraPPE-LJ model of Martin and Siepmann for ethane and
      Wick et al. for ethylene and (ii) AUA4-LJ model of Ungerer et al. for ethane and
      Bourasseau et al. for ethylene. These models are used to study the adsorption of
      ethane and ethylene on graphitized thermal carbon black. It is found that the
      solid-fluid binary interaction parameter is a function of adsorbate and
      temperature, and the adsorption isotherms and heat of adsorption are well
      described by both the UA-TraPPE and AUA models, although the UA-TraPPE model
      performs slightly better. However, the local distributions predicted by these two
      models are slightly different. These two models are used to explore the two
      dimensional condensation for the graphitized thermal carbon black, and these
      values are 110 K for ethylene and 120 K for ethane.

PMID- 15568839
TI  - Viscoelastic properties of cationic starch adsorbed on quartz studied by QCM-D.
AB  - The adsorption and viscoelastic properties of layers of a cationic
      polyelectrolyte (cationic starch, CS, with 2-hydroxy-3-trimethylammoniumchloride
      as the substituent) adsorbed from aqueous solutions (pH 7.5, added NaCl 0, 1,
      100, and 500 mM) on silica were studied with a quartz crystal microbalance with
      dissipation (QCM-D). Three different starches were investigated (weight-average
      molecular weights M(w) approximately 8.7 x 10(5) and 4.5 x 10(5) with degree of
      substitution DS = 0.75 and M(w) approximately 8.8 x 10(5) with DS = 0.2). At low
      ionic strength, the adsorbed layers are thin and rigid and the amount adsorbed
      can be calculated using the Sauerbrey equation. When the ionic strength is
      increased, significant changes take place in the amount of adsorbed CS and the
      viscoelasticity of the adsorbed layer. These changes were analyzed assuming that
      the layer can be described as a Voigt element on a rigid surface in contact with
      purely viscous solvent. It was found that CS with low charge density forms a
      thicker and more mobile layer with higher viscosity and elasticity than CS with
      high charge density. The polymers adsorbed on the silica even when the ionic
      strength was so high that electrostatic interactions were effectively screened.
      At this high ionic strength, it was possible to study the effect of molecular
      weight and molecular weight distribution of the CS on the properties of the
      adsorbed film. Increasing the molecular weight of CS resulted in a larger
      hydrodynamic thickness. CS with a narrow molecular weight distribution formed a
      more compact and rigid layer than broadly distributed CS, presumably due to the
      better packing of the molecules.

PMID- 15568840
TI  - Nitrogen and oxygen mixture adsorption on carbon nanotube bundles from molecular
      simulation.
AB  - The adsorption of a nitrogen and oxygen mixture (air) on two types of single
      walled carbon nanotube bundles at both sub- and supercritical temperatures is
      studied using grand canonical Monte Carlo molecular simulation. On an infinite
      periodic hexagonal bundle without an external surface, adsorption at a
      subcritical temperature is of type I. With increasing pressure, nitrogen
      adsorption first increases and then decreases until saturation; oxygen adsorption
      continues increasing, displacing nitrogen, until saturation. Both nitrogen and
      oxygen first form annuli inside the nanotubes, then with increased coverage they
      occupy the nanotube centers, and at the highest coverage some oxygen also adsorbs
      in the interstitial channels between the nanotubes. The selectivity of nitrogen
      over oxygen decreases with increasing pressure and reaches a constant near
      saturation. Adsorption at a supercritical temperature is also of type I, with
      both nitrogen and oxygen adsorption increasing with increasing pressure, though
      the selectivity of nitrogen to oxygen first increases slightly and then decreases
      with increasing pressure. On a small isolated hexagonal bundle with an external
      surface, adsorption at a subcritical temperature is of type II. With increasing
      pressure, nitrogen adsorption first increases, then decreases, and finally
      increases again due to wetting by liquid air, while oxygen adsorption increases
      continually. Both nitrogen and oxygen adsorb first at the internal annuli and at
      the grooves, and with increasing pressure, they then adsorb at the ridges and at
      the nanotube centers; at higher pressures, only oxygen adsorbs in the
      interstitial channels, and multilayer adsorption and wetting occur on the
      external surface as the bulk phase approaches saturation. The selectivity, like
      that of subcritical temperature adsorption on the infinite periodic bundle,
      decreases with increasing pressure and reaches a constant upon wetting.
      Adsorption at a supercritical temperature is of type I, with both nitrogen and
      oxygen adsorption increasing with increasing pressure. The selectivity of
      nitrogen to oxygen, like that of supercritical temperature adsorption on the
      infinite periodic bundle, first increases slightly and then decreases with
      increasing pressure. These results indicate that the adsorption selectivity
      strongly depends on temperature but only weakly depends on the type of the bundle
      and that a nitrogen--oxygen mixture (air) might be separated by competitive
      adsorption on the carbon nanotube bundles.

PMID- 15568841
TI  - Wettability interpretation of oxygen plasma modified poly(methyl methacrylate).
AB  - Poly(methyl methacrylate) (PMMA) has been modified via a dc pulsed oxygen plasma
      for different treatment times. The modified surfaces were characterized by X-ray
      photoelectron spectroscopy (XPS), optical profilometer, zeta potential, and
      advancing contact angle measurements. The measured advancing contact angles of
      water decreased considerably as a function of discharge. Several oxygen-based
      functionalities (carbonyl, carboxyl, carbonate, etc.) were detected by XPS, while
      zeta potential measurements confirmed an increase in negative charge for the
      treated PMMA surface. Evaluating the correlation between the concentration of
      polar chemical species and zeta potential, we found that increase in surface
      hydrophilicity results from the coeffect due to incorporation of oxygen
      functional groups and creation of charge states. The electrical double layer
      (EDL) effect was also considered in contact angle interpretation by introducing
      an additional surface tension term into Young's equation. We also found that EDL
      contribution to the solid-liquid interfacial tension is negligible and can be
      safely ignored for the systems considered here.

PMID- 15568842
TI  - Halogen-substituted thiophenol molecules on Cu(111).
AB  - Para-halosubstituted thiophenols (X-TPs, where X is Br, Cl, or F) form ordered
      islands and monolayers on Cu(111) at temperatures as low as 81 K. At incomplete
      coverages, all X-TPs adsorb with the dehydrogenated thiol group attached to the
      substrate and the substituted ring inclined toward the surface, as verified
      experimentally and theoretically. The structure of ordered islands has a
      pronounced dependence on the nature of the halogen substituent: while
      unsubstituted TP and pentafluoro-TP molecules do not self-assemble into extended
      ordered patterns at 81 K, X-TP molecules form a range of different structures
      which depend both on the size and electronegativity of the substituent, as well
      as on the coverage.

PMID- 15568843
TI  - Headgroup and hydrocarbon tail effects on the surface tension of sugar-based
      surfactant solutions.
AB  - Measurements of surface tension isotherms were conducted for water solutions of
      pure and mixed n-decyl-beta-d-glucopyranoside (C(10)-Glu) and n-decyl-beta-d
      maltopyranoside (C(10)-Mal) surfactants. By applying the Gibbs surface tension
      equation, the surface densities of Glu and Mal were derived for different
      compositions and concentrations. The surface fractions were compared with
      theoretically calculated values where the headgroups were modeled as hard disks.
      Satisfactory agreement was found for hard-disk sizes of 22.9 and 11.3 A(2) in the
      case of a 1:1 mixture. The results of the hard-disk calculations were employed to
      estimate the configurational free energy of the n-decyl-hydrocarbon chain. The
      results obtained agree well with previous calculations for the n-dodecyl chain.
      Comparison with n-dodecyl beta-d-maltopyranoside (C(12)-Mal) indicated a further
      contribution, with the longer hydrocarbon chain giving rise to a higher surface
      tension in good agreement with data for hydrocarbon liquids. Furthermore, the
      interpenetration of the headgroup into the hydrocarbon film was studied by means
      of comparing surface-tension data for n-decyl- and n-dodecyl-ethylene-oxide-based
      surfactants and n-decyl- and n-dodecyl-beta-d-thiomaltopyranosides (C(10)-S-Mal
      and C(12)-S-Mal, respectively) and -maltopyranosides. It was found that
      lengthening the tetra(etylene oxide) chain by one segment affects the surface
      tension only marginally, indicating little interpenetration of the additional
      ethylene-oxide group into the hydrocarbon film. For the thiomaltosides, however,
      the corresponding effect was found to be remarkably high.

PMID- 15568844
TI  - Enhanced rates of electrolytic styrene epoxidation catalyzed by cross-linked
      myoglobin-poly(L-lysine) films in bicontinuous microemulsions.
AB  - Redox proteins attached to surfaces designed for biocatalysis hold promise for
      future clean synthetic routes. It is advantageous for these biocatalysts to
      operate in low-toxicity fluids with a high capacity to dissolve reactants. Here
      we report cross-linked films of myoglobin (Mb) and poly(L-lysine) (PLL)
      chemically attached to oxidized carbon cloth cathodes that in microemulsions
      feature the protein in a water-rich film environment with reactant in an oil-rich
      environment. These cross-linked Mb/PLL films were the most stable in
      microemuslions and had the largest turnover rates for epoxidation of styrene
      compared to lightly cross-linked or uncross-linked Mb/poly(styrene sulfonate)
      films. Up to 40-fold larger turnover rates were found in bicontinuous
      microemulsions compared to oil-in-water microemulsions and micelles. Enhanced
      turnover rates are correlated with up to 10-fold faster mass transport of solutes
      in the oil phases of the bicontinuous fluids.

PMID- 15568845
TI  - Microbial adhesion to poly(ethylene oxide) brushes: influence of polymer chain
      length and temperature.
AB  - Glass surfaces were modified by end-grafting poly(ethylene oxide) (PEO) chains
      having molecular weights of 526, 2000, or 9800 Da. Characterization using water
      contact angles, ellipsometry, and X-ray photoelectron spectroscopy confirmed the
      presence of the PEO brushes on the surface with estimated lengths in water of 2.8
      , 7.5-, and 23.7-nm, respectively. Adhesion of two bacterial (Staphylococcus
      epidermidis and Pseudomonas aeruginosa) and two yeast (Candida albicans and
      Candida tropicalis) strains to these brushes was studied and compared to their
      adhesion to bare glass. For the bacterium P. aeruginosa and the yeast C.
      tropicalis, adhesion to the 2.8-nm brush was comparable to their adhesion on bare
      glass, whereas adhesion to the 7.5- and 23.7-nm brushes was greatly reduced. For
      S. epidermidis, adhesion was only slightly higher to the 2.8-nm brush than that
      to the longer brushes. Adhesion of the yeast C. albicans to the PEO brushes was
      lower than that to glass, but no differences in adhesion were found between the
      three brush lengths. After passage of an air bubble, nearly all microorganisms
      adhering to a brush were removed, irrespective of brush length, whereas retention
      of the adhering organisms on glass was much higher. No significant differences
      were found in adhesion nor retention between experiments conducted at 20 and
      those conducted at 37 degrees C.

PMID- 15568846
TI  - Reactions of ammonia on stoichiometric and reduced TiO(2)(001) single crystal
      surfaces.
AB  - The reaction of NH(3) on the surface of the 011-faceted structure of the
      TiO(2)(001) single crystal is studied and compared to that on the O-defected
      surface. Temperature-programmed desorption (TPD) conducted after NH(3) adsorption
      at 300 K shows only molecular desorption at 340 K. Modeling of TPD signals as a
      function of surface coverage indicated that the activation energy, E(d), and pre
      exponential factor, v(eff), decrease with increasing coverage. Near zero surface
      coverage, E(d) was found to be equal to 92 kJ/mol and v(eff) to be close to
      10(13) /s. Both parameters decreased to approximately 52 kJ/mol and approximately
      10(7) /s at saturation coverage. The decrease is due to a repulsive interaction
      of adsorbed NH(3) molecules on the surface. Computing of the TPD results show
      that saturation is obtained at 1/2 monolayer coverage (referred to Ti atoms).
      Both the amount and shape of NH(3) peak change on the reduced (Ar(+)-sputtered)
      surfaces. The desorption peak at 340 K is considerably attenuated on mildly
      reduced surfaces (TiO( approximately )(1.9)) and has totally disappeared on the
      heavily reduced surfaces (TiO(1.6)(-)(1.7)), where the main desorption peak is
      found at 440 K. This 440-K desorption is most likely due to NH(x) + H
      recombination resulting from ammonia dissociation upon adsorption on Ti atoms in
      low oxidation states.

PMID- 15568847
TI  - On the mechanism of nanopore filling of SAPO-5 molecular sieve by nitrogen
      molecules.
AB  - SAPO-5 molecular sieve was synthesized according to patent literature and
      characterized with X-ray diffraction, electron microscopy (SEM, TEM), and solid
      state magic angle spinning NMR spectroscopy. The material of particles in the
      micrometer region was found to consist of ca. 20 nm microcrystallites packed in
      mostly parallel orientation to ca. 200 nm sized agglomerates. The nitrogen
      adsorption isotherm was measured at 77.6 K over ca. 7 decades of pressure up to
      pore saturation. The course of the isotherm is interpreted to consist of filling
      of the nanopores (diameter, 0.73 nm) up to 2N(2)/unit cell, subsequent multilayer
      adsorption on the outer surface of the agglomerates, and, finally, pore
      condensation in the interparticle adsorption space. The nanopore adsorption can
      be quantitatively reproduced with the statistical mechanical model of a quasi one
      dimensional lattice gas taking intermolecular interactions into account. The
      evaluated energy parameters are of physically reasonable magnitude and agree with
      literature data. The multilayer part of the adsorption isotherm can be well
      represented by the Brunauer-Emmett-Teller model yielding a specific outer space
      area (63 m(2) g(-)(1)) which is consistent with estimated geometrical and pore
      size analysis data.

PMID- 15568848
TI  - A comparative study of hydroxide adsorption on the (111), (110), and (100) faces
      of silver with cyclic voltammetry, ex situ electron diffraction, and in situ
      second harmonic generation.
AB  - Hydroxide adsorption on the (111), (110), and (100) faces of silver electrodes
      from mixed NaOH/NaF solution is studied using cyclic voltammetry and in situ
      second harmonic generation (SHG). Cyclic voltammograms for the three low index
      silver planes in alkaline electrolytes are for the first time compared. They show
      two pairs of anodic and cathodic peaks in the potential interval below the
      equilibrium Ag/Ag(2)O potential. These are attributed to the specific adsorption
      of hydroxide ions followed by submonolayer oxide formation. The differences in
      the cyclic voltammograms for the (111), (110), and (100) planes are attributed to
      different (i) work functions, (ii) surface atomic densities, and (iii)
      corrugation potentials for these surfaces. Ex situ low energy electron
      diffraction (LEED) and reflection high energy electron diffraction (RHEED) show
      that disordered adlayers are formed on Ag(111) and Ag(100), in contrast to
      Ag(110), where ordered structures are produced in the region of the first pair of
      current peaks. In the region of the second pair of peaks, LEED indicates
      disordered oxide phases on each crystal plane and RHEED shows the presence of
      small islands of c(2 x 2) structure at some potentials on (110) and (100). SHG
      measurements were performed (i) in the potential scan mode at constant rotational
      angle and (ii) at constant potential as a function of the rotational angle. The
      isotropic (for the (111), (110), and (100) planes) and anisotropic (for the (110)
      and (111) planes) contributions to the SHG intensity were calculated by fitting
      the experimental data and are discussed in terms of their dependence on the
      charge density at the interface, on hydroxide adsorption, and on submonolayer
      oxide formation.

PMID- 15568849
TI  - Adsorption, desorption, and conversion of thiophene on H-ZSM5.
AB  - The dynamics and stoichiometry of thiophene adsorption and of rearrangements of
      thiophene-derived adsorbed species in O(2), He, H(2), and C(3)H(8) carriers were
      measured using chromatographic methods and mass spectrometry on H-ZSM5 and H-Y
      zeolites. Thiophene adsorption obeyed Langmuir isotherms on both zeolites.
      Adsorption uptakes were 1.7 and 2.8 thiophene/Al at 363 K on H-ZSM5 and H-Y
      zeolites, respectively, after removal of physisorbed thiophene. These
      stoichiometries differed for these two zeolite structures but did not depend on
      their Al content (Si/Al = 13-85). Adsorption from a thiophene-toluene mixture
      showed thiophene selectivities ( approximately 10) greater than expected from van
      der Waals interactions. These adsorption stoichiometries, without contributions
      from physisorption, and the color changes detected indicate that thiophene
      adsorption occurs concurrently with oligomerization on acidic OH groups and that
      oligomer size depends on spatial constraints within channels. Thiophene oligomers
      decompose at approximately 534 K during subsequent thermal treatment to form
      molecular thiophene with all carriers, leaving behind unsaturated thiophene
      derived species with a 0.9-1.1 thiophene/Al stoichiometry, confirming the
      specificity of OH groups and the oligomeric nature of bound thiophene during
      adsorption at 363 K. With He, H(2), and C(3)H(8), residual thiophene-derived
      species desorb as stable fragments, such as H(2)S, ethene, propene, arenes, and
      heavier organosulfur compounds (methylthiophene and benzothiophene) during
      thermal treatment; they also form unsaturated organic deposits that cannot desorb
      without hydrogenation events. H(2) and C(3)H(8) remove larger amounts of adsorbed
      species as unreacted thiophene than He, suggesting that dehydrogenation reactions
      are inhibited or reversed by a hydrogen source. C(3)H(8) removes a larger
      fraction of thiophene-derived intermediates as hydrocarbons and organosulfur
      compounds than H(2) or He; thus, hydrogen atoms formed during C(3)H(8)
      dehydrogenation are more effective in the removal of unsaturated deposits than
      those formed from H(2). Thiophene-derived adsorbed species are completely removed
      only with O(2)-containing streams at 873 K, a process that fully recovers initial
      adsorption capacities. This study provides a rigorous assessment of the nature
      and specificity of thiophene adsorption processes on acidic OH groups and of the
      identity and removal pathways of adsorbed species in various reactive
      environments.

PMID- 15568850
TI  - Loosely packed self-assembled monolayer of N-hexadecyl-3,6-di(p
      mercaptophenylacetylene)carbazole on gold and its application in biomimetic
      membrane research.
AB  - Dithiols of N-hexadecyl-3,6-di(p-mercaptophenylacetylene)carbazole (HDMC) have
      been synthesized and employed to form self-assembled monolayers (SAMs) on gold.
      One characteristic of the HDMC molecule is its peculiar molecular structure
      consisting of a large and rigid headgroup and a small and flexible alkyl-chain
      tail. HDMC adsorbates can attach to gold substrates by a strong Au-S bond with
      weak van der Waals interactions between the alkyl-chain tails, leading to a
      loosely packed hydrophobic SAM. In this way we can couple hybrid bilayer
      membranes (HBMs) to gold surfaces with more likeness to a cell bilayer than the
      conventional HBMs based on densely packed long-chain alkanethiol SAMs. The
      insulating properties and stability of the HDMC monolayer as well as the
      HDMC/lipid bilayer on gold have been investigated by electrochemical techniques
      including cyclic voltammetry and impedance spectroscopy. To test whether the
      quality of the bilayer is sufficiently high for biomimetic research, we
      incorporated the pore-forming protein alpha-hemolysin) and the horseradish
      peroxidase into the bilayers, respectively. Experimental results demonstrated
      that this type of loosely packed hydrophobic SAM has great potential in
      biomimetic bilayer research and biosensor application.

PMID- 15568851
TI  - The use of surface tension to predict the formation of 2D arrays of latex spheres
      formed via the Langmuir-Blodgett-like technique.
AB  - Highly ordered hexagonal arrays of latex spheres on highly ordered pyrolytic
      graphite (HOPG) have been prepared from a Langmuir-Blodgett-like (LB-like)
      technique using both polymers and surfactants as spreading agents. The role of
      spreading agent concentration in forming a well-ordered, stable monolayer at the
      air-liquid interface was studied by means of atomic force microscopy, scanning
      electron microscopy, optical microscopy, and surface tension measurements for
      three different systems: a nonionic surfactant, octylphenoxy
      poly(ethyleneoxy)ethanol (Igepal CO 630); an anionic surfactant, sodium dodecyl
      sulfate; and a low-molecular-weight, water-soluble polymer, polyacrylamide. For
      both the anionic surfactant and the water soluble polymer, a correlation was
      found between a unique feature in surface tension measurements of the latex
      spreading agent mixture and the concentrations at which hexagonal arrays of latex
      spheres form on the surface of HOPG. For the nonionic surfactant, no ordered
      structures were found on HOPG for any surfactant concentration, consistent with
      no appearance of the unique feature in surface tension measurements. These
      results show that a tensiometer can be used to determine the conditions under
      which well-ordered latex films have the possibility of forming on a substrate
      using the LB-like technique; however, other factors, such as pulling speed and
      surface chemistry, play a role as well.

PMID- 15568852
TI  - Dielectrophoretic micropatterning with microparticle monolayers covalently linked
      to glass surfaces.
AB  - Two-dimensional micropatterns of microparticles were fabricated on glass
      substrates with negative dielectrophoretic force, and the patterned
      microparticles were covalently bound on the substrate via cross-linking agents.
      The line and grid patterns of microparticles were prepared using the repulsive
      force of negative dielectrophoresis (n-DEP). The template interdigitated
      microband array (IDA) electrodes (width and gap 50 mum) were incorporated into
      the dielectrophoretic patterning cell with a fluidic channel. The microstructures
      on the glass substrates with amino or sulfhydryl groups were immobilized with the
      cross-linking agents disuccinimidyl suberate (DSS) and m-maleimidobenzoyl-N
      hydroxy-succinimide ester (MBS). Diaphorase (Dp), a flavoenzyme, was selectively
      attached on the patterned microparticles using the maleimide groups of MBS. The
      enzyme activity on the patterned particles was electrochemically characterized
      with a scanning electrochemical microscope (SECM) in the presence of NADH and
      ferrocenylmethanol as a redox mediator. The SECM images proved that Dp was
      selectively immobilized onto the surface of microparticles to maintain its
      catalytic activity.

PMID- 15568853
TI  - Surface phase diagrams: evidence of molecular arrangements at the aqueous
      solution/solid interface.
AB  - Surface state changes described as phase transitions or simple molecular
      rearrangements have become a key issue in modern science. Indeed, they have an
      impact on the development of numerous (nano)technologies; they are also involved
      in biochemical and chemical mechanisms at the molecular level and also in
      environmental phenomena. At last, they have been at the origin of flourishing
      statistical descriptions that have illuminated new and very interesting aspects
      of surface behaviors. Here, to obtain still lacking coherent sets of experimental
      data on systems in which molecular interactions and thermodynamic properties are
      different, the adsorption behaviors of three aqueous mixtures in contact with a
      dense and homogeneous silica were studied versus concentrations and temperatures.
      Of course, these mixtures displayed very different bulk phase properties. Their
      stairlike isotherms are interpreted through surface phase diagrams; each of them
      is very similar to the corresponding bulk phase diagram. Their comparison gives
      new insights into the different surface states, the role of solvent in the
      surface, and the probable molecular mobility.

PMID- 15568854
TI  - X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure
      study of water adsorption on pyridine-terminated thiolate self-assembled
      monolayers.
AB  - Adsorption of water on self-assembled monolayers (SAMs) of 4-(4
      mercaptophenyl)pyridine on gold at low temperatures under ultrahigh vacuum
      conditions is studied by synchrotron radiation X-ray photoelectron and absorption
      spectroscopy. Water adsorption induces a strong modification of the chemical
      state of the pyridine N atoms at the SAM/ice interface, indicative for strong H
      bonding and partial proton transfer between water molecules and pyridine
      moieties. Additionally, the initial molecular orientation within the SAM is
      changed upon formation of an adsorbed water multilayer.

PMID- 15568855
TI  - AFM study of the behavior of polystyrene and glass particles during the
      electrodeposition of copper.
AB  - In this paper, the behavior of polystyrene and glass particles on a copper
      electrode during the electrodeposition of copper was studied using an atomic
      force microscope (AFM). Polystyrene or glass particles glued to the tip of the
      AFM cantilever were kept in contact with the surface of the electrode. The
      surface forces between the polystyrene or glass particle and the copper electrode
      were measured before, during, and after electrodeposition. These experiments
      revealed that glass particles do not make contact with the electrode, probably
      due to the repulsive hydration force. Polystyrene particles, on the other hand,
      make contact with the electrode, due to the attractive hydrophobic force. The AFM
      experiments were correlated with sedimentation co-deposition experiments of
      polystyrene and glass particles with copper. It was found that 80% of the
      polystyrene particles added to the plating solution incorporated with copper,
      while only 0.25% of the glass particles co-deposited under the same conditions.

PMID- 15568856
TI  - Coulombic interactions on the deposition and rotational mobility distributions of
      dyes in polyelectrolyte multilayer thin films.
AB  - We employed negatively charged fluorescein (FL), positively charged rhodamine 6G
      (R6G), and neutral Nile Red (NR) as molecular probes to investigate the influence
      of Coulombic interaction on their deposition into and rotational mobility inside
      polyelectrolyte multilayer (PEM) films. The entrapment efficiency of the dyes
      reveals that while Coulombic repulsion has little effect on dye deposition,
      Coulombic attraction can dramatically enhance the loading efficiency of dyes into
      a PEM film. By monitoring the emission polarization of single dye molecules in
      polyethylenimine (PEI) films, the percentages of mobile R6G, NR, and FL were
      determined to be 87 +/- 4%, 76 +/- 5%, and 68 +/- 3%, respectively. These
      mobility distributions suggest that cationic R6G enjoys the highest degree of
      rotational freedom, whereas anionic FL shows the least mobility because of
      Coulombic attraction toward cationic PEI. Regardless of charges, this high
      percentage of mobile molecules is in stark contrast to the 5-40% probe mobility
      reported from spun-cast polymer films, indicating that our PEI films contain more
      free volume and display richer polymer dynamics. These observations demonstrate
      the potential of using isolated fluorescent probes to interrogate the internal
      structure of a PEM film at a microscopic level.

PMID- 15568857
TI  - Electrochemical redox control of ferrocene using a supramolecular assembly of
      ferrocene-linked C(60) derivative and metallooctaethylporphyrin array on a
      Au(111) electrode.
AB  - Supramolecular assembled layers of ferrocene-linked C(60) derivative (C(60)Fc)
      and various metal ions coordinated to octaethylporphyrin (MOEP) were formed on
      the surface of a Au(111) single-crystal electrode by immersing the Au substrate
      successively into a benzene solution containing MOEP and one containing C(60)Fc
      molecules. The MOEPs used were zinc(II) (ZnOEP), cobalt(II) (CoOEP), copper(II)
      (CuOEP), and iron(III) chloride (FeClOEP) of OEP (2,3,7,8,12,13,17,18-octaethyl
      21H,23H-porphine). The molecules of C(60)Fc directly attached to the Au(111)
      electrode showed poorly defined electrochemical redox response, whereas a clear
      electrochemical redox reaction of the ferrocene group in the C(60)Fc molecule was
      observed at 0.78 V versus reversible hydrogen electrode on ZnOEP, CoOEP, and
      CuOEP adlayers, but not on the FeClOEP adlayer. Adlattices of the underlying
      layer and the top layer of C(60)Fc were determined by in situ scanning tunneling
      microscopy. Adlayer structures of MOEP were independent of the central metal ion;
      that is, MOEP molecules were arranged hexagonally with two different
      orientations. Highly ordered C(60)Fc arrays were formed with 1:1 composition on
      the ZnOEP-, CoOEP-, and CuOEP-modified Au(111) surface, whereas a disordered
      structure of C(60)Fc was found on the FeClOEP-modified Au(111) surface. The
      presence of Cl ligand was found to prevent the formation of supramolecularly
      assembled layers with C(60)Fc molecules, resulting in an ill-defined unclear
      electrochemical response of the Fc group. The well-defined electrochemical
      response of the Fc group in C(60)Fc was clearly due to the control of orientation
      of C(60)Fc molecules.

PMID- 15568858
TI  - Comparison of antibody--antigen interactions on collagen measured by conventional
      immunological techniques and atomic force microscopy.
AB  - We have developed a means of using atomic force microscopy (AFM) to repeatedly
      localize a small area of interest (4 x 4 microm(2)) within a 0.5-cm(2) area on a
      heterogeneous sample, to obtain and localize high-resolution images and force
      measurements on nonideal samples (i.e., samples that better reflect actual
      biological systems, not prepared on atomically flat surfaces). We demonstrate the
      repeated localization and measurement of unbinding forces associated with
      antibody--antigen (ab--ag) interactions, by applying AFM in air and in liquid to
      visualize and measure polyclonal ab--ag interactions, using chicken collagen as a
      model system. We demonstrate that molecular interactions, in the form of ab--ag
      complexes, can be visualized by AFM when secondary antibodies are conjugated to
      20-nm colloidal gold particles. We then compare those results with established
      immunological techniques, to demonstrate broader application of AFM technology to
      other systems. Data from AFM studies are compared with results obtained using
      immunological methods traditionally employed to investigate ab--ag interactions,
      including enzyme-linked immunosorbent assay, immunoblotting, and in situ
      immunofluorescence. Finally, using functionalized AFM tips with a flexible tether
      [poly(ethylene glycol) 800] to which a derivatized antibody was attached, we
      analyzed force curve data to measure the unbinding force of collagen antibody
      from its antigen, obtaining a value of approximately 90 +/- 40 pN with a MatLab
      code written to automate the analyses of force curves obtained in force--volume
      mode. The methodology we developed for embedded collagen sections can be readily
      applied to the investigation of other receptor--ligand interactions.

PMID- 15568859
TI  - FTIR study of the ethanol electrooxidation on Pt(100) modified by osmium
      nanodeposits.
AB  - In the present work, ethanol electrooxidation on a Pt(100) electrode modified by
      different coverage degrees of osmium nanoislands obtained by spontaneous
      depositions, was extensively studied employing in situ FTIR spectroscopy. A
      collection of spectra of the ethanol adsorption and oxidation processes was
      acquired during the first series of a positive potential step, to determine the
      intermediate species, as well as the main products formed. The spectroscopic
      results obtained were correlated with conventional electrochemical results
      obtained by cyclic voltammetry. It was shown that the catalytic activity of
      Pt(100) for ethanol oxidation increases significantly after osmium deposition and
      that the mechanistic pathway for this reaction depends directly on the osmium
      coverage degree. Thus, for low osmium coverage (theta;( Os) up to 0.15) the
      formation of CO as an intermediate was favored and hence the full oxidation of
      adsorbed ethanol to CO(2) was increased. For higher osmium coverages (theta;(Os)
      up to 0.33), the higher the coverage is, the more the direct ethanol oxidation to
      acetaldehyde and acetic acid is favored. For osmium coverage degree of 0.40, the
      catalytic activity of the electrode for ethanol oxidation decreased. On an almost
      complete osmium layer (theta;(Os) = 0.92) obtained by electrodeposition at 50 mV
      vs reversible hydrogen electrode, the catalytic activity for ethanol oxidation
      shows a much lower value.

PMID- 15568860
TI  - Effects of silicone acrylate on morphology, kinetics, and surface composition of
      photopolymerized acrylate mixtures.
AB  - Films (ca. 150 microm thick) of twelve acrylate mixtures, which contained various
      proportions of hydrocarbon acrylates [mainly oligo(ethylene glycol) diacrylate,
      (OEGDA)] and small amounts of a silicone hexaacrylate (in proportion of 5% or
      less), were cured on a nickel substrate, and X-ray photoelectron spectroscopy
      analysis of the nickel-side surface compositions showed that for formulations
      with and without the silicone hexaacrylate, this surface was enriched with OEGDA
      and saturated (up to 50%) with the silicone hexaacrylate, respectively. The
      silicone hexaacrylate phase-separated and formed micelles which migrated to the
      resin-nickel interface. Silicone hexaacrylate, inherently less reactive, also
      significantly slowed the photopolymerization of the mixtures. The sequential
      homopolymerization of OEGDA and silicone hexaacrylate in a formulation was
      elicited using real-time Fourier transform infrared spectroscopy. The design-of
      experiment approach was used to quantify the influence of the components on
      gelation time and the nickel-side surface composition as well as provide the
      statistical models to predict these two properties for new compositions.

PMID- 15568861
TI  - Microscopic visualization of alamethicin incorporation into model membrane
      monolayers.
AB  - Lipid interactions and cooperative assembly properties are fundamental
      determinants for the action of antimicrobial membrane-active peptides. Here we
      analyze the interactions and aggregation properties of alamethicin, an
      antimicrobial pore-forming peptide, with films formed at the air/water interface.
      Surface-area/pressure isotherms, Brewster angle microscopy, and fluorescence
      confocal microscopy provided detailed information on the morphologies and
      structural properties of the peptide and its effect on the film components. The
      pressure-area analysis and microscopy experiments facilitated unprecedented
      visualization of the structural consequences of alamethicin association at the
      air/water interface, with pure phospholipid films, and within mixed
      phospholipid/polydiacetylene (PDA) films. The analysis exposed the kinetic
      features and the interplay between the peptide aggregates and film constituents.
      In particular, the results demonstrate the use of phospholipid/PDA film
      assemblies for studying membrane-peptide association and interactions within two
      dimensional films.

PMID- 15568862
TI  - Patterned supported lipid bilayers and monolayers on poly(dimethylsiloxane).
AB  - A simple and practical method for patterning supported lipid bilayers on
      poly(dimethylsiloxane) is presented. By using electron microscopy grids to
      laterally control the extent of plasma oxidation, the substrate is partitioned
      into regions of different hydrophilicities. Addition of vesicles then results in
      the spontaneous formation of lipid bilayers and monolayers side-by-side on the
      surface, separated by regions that contain no lipid and/or a region with adhering
      vesicles. By using millimeter-sized plastic masks we are able to control the
      formation of these lipid structures on macroscopic patches by simply varying the
      plasma-cleaning time. For the first time, we are able to influence, in a
      controlled fashion, the chemical composition of a substrate in such a way that it
      supports fluid lipid monolayers, rejects lipid adhesion, adsorbs intact lipid
      vesicles, or supports fluid bilayers.

PMID- 15568863
TI  - DNA attachment chemistry at the flexible silicone elastomer surface: toward
      disposable microarrays.
AB  - This paper describes the preparation and surface characterization of maleimide
      activated silicone elastomer (PDMS(MCC)) followed by covalent functionalization
      using thiol-terminated DNA sequences (primary oligo). The stability of this
      attachment chemistry was demonstrated by the retention of the primary oligo
      through the process of hybridization with a labeled complementary DNA sequence.
      In these studies, the hybridized labeled DNA oligomers were detected using
      confocal fluorescence microscopy. We have employed a vapor deposition technique
      in which a plasma-treated silicone elastomer (PDMS(OH)) was exposed to vapors of
      3-(aminopropyl)triethoxysilane (APTS) under vacuum, to yield the amine
      functionalized silicone elastomer (PDMS(NH)(2)). PDMS(NH)(2) was further coupled
      with a heterofunctional cross-linker, sulfosuccinimidyl-4-(N
      maleimidomethyl)cyclohexane-1-carboxylate to obtain PDMS(MCC). The surface
      functionalities of the elastomers were characterized using contact angle
      measurements and X-ray photoelectron spectroscopy. Surface-modified silicone
      elastomers appear to be promising substrates for use as substrates for disposable
      microarrays.

PMID- 15568864
TI  - Adhesion of bacterial exopolymers to alpha-FeOOH: inner-sphere complexation of
      phosphodiester groups.
AB  - Extracellular polymeric substances (EPS) constitute a heterogeneous mixture of
      polyelectrolytes that mediate biomineralization and bacterial adhesion and
      stabilize biofilm matrixes in natural and artificial environments. Although
      nucleic acids are exuded extracellularly and are purported to be required for
      biofilm formation, direct evidence of the active mechanism is lacking. EPS were
      extracted from both Bacillus subtilis (a gram-positive bacterium) and Pseudomonas
      aeruginosa (a gram-negative bacterium) and their interaction with the goethite
      (alpha-FeOOH) surface was studied using attenuated total internal reflection
      infrared spectroscopy. Correspondence between spectral data and quantum chemical
      calculations demonstrate that phosphodiester groups of nucleic acids mediate the
      binding of EPS to mineral surfaces. Our data indicate that these groups emerge
      from the EPS mixture to form monodentate complexes with Fe centers on the
      goethite (alpha-FeOOH) surface, providing an energetically stable bond for
      further EPS or cell adhesion.

PMID- 15568865
TI  - Supported cell mimetic monolayers and their interaction with blood.
AB  - Surface modification using supported monolayers of phosphorylcholine containing
      phospholipids has been an accepted strategy for developing blood-contacting
      materials. We present a detailed study of the blood compatibility of the
      supported monolayers of phospholipid, glycolipid, and cholesterol (Chol) binary
      and ternary lipid combinations using in vitro techniques. The packing and
      orientation of these monolayers have been correlated with the blood
      compatibility. We have used phosphatidylcholine (PTC) for phospholipid,
      galactocerebroside (Gal) for glycolipid, and Chol based on the headgroup
      structure to represent the major lipid components of the endothelial luminal cell
      membrane. The interfacial behavior of various combinations of PTC, Gal, and Chol
      monolayers have been studied at the air/water interface and deposited on
      hydrophobic polycarbonate (PC) polymer substrates with the help of the Langmuir
      Blodgett trough. The packing and orientation of the supported monolayers have
      been varied by means of changing the lipid composition rather than the deposition
      parameters. This approach seems to be more similar to the in vivo conditions. The
      different supported monolayer surfaces prepared accordingly are (1) a closely
      packed ordered hydrophobic surface, PC modified with the combination PTC/Chol/Gal
      (1:0.35:0.125), (2) a loosely packed ordered hydrophobic surface, PC modified
      with the combination PTC/Chol (1:0.35), and (3) a closely packed ordered
      hydrophilic surface, PC modified with the combination PTC/Chol (1:0.7). An
      optimized modified surface (PTC/Chol/Gal, 1:0.35:0.125) has been identified on
      the basis of the maximum transfer ratio from the air/water interface and
      characterized by using atomic force microscopy. The concentration of Chol has
      been found to be an important parameter, which influences the transfer ratio. The
      Gal improves the monolayer integrity under a reduced Chol concentration. The
      blood compatibility of these supported monolayers was studied by protein
      adsorption, blood cell adhesion, and calcification. The tightly packed ordered
      hydrophobic surface (PTC/Chol/Gal, 1:0.35:0.125), has been found to be more blood
      compatible because of reduced blood cell adhesion and calcification. This surface
      also promotes albumin adsorption and may be the reason for the reduced platelet
      activation, while in the case of the loosely packed ordered hydrophobic surface
      (PTC/Chol, 1:0.35) the protein adsorption also has been reduced along with the
      blood cell adhesion and calcification. When the ordered hydrophilic surface
      (PTC/Chol, 1: 0.7) of the monolayer has been exposed, the blood cell adhesions as
      well as the overall protein adsorption were significantly reduced. However, the
      packing of the phosphorylcholine moieties of the polar headgroup has been
      affecting the calcification on the surface. We have observed an increase in
      calcification to the surface modified with the loosely packed polar headgroup,
      from a relative study on chitosan and chitosan modified with the monolayer of
      PTC. These findings are helpful for the surface modifications for blood
      contacting materials using this strategy.

PMID- 15568866
TI  - Protein surface patterning using nanoscale PEG hydrogels.
AB  - We have used focused electron-beam cross-linking to create nanosized hydrogels
      and thus present a new method with which to bring the attractive biocompatibility
      associated with macroscopic hydrogels into the submicron length-scale regime.
      Using amine-terminated poly(ethylene glycol) thin films on silicon substrates, we
      generate nanohydrogels with lateral dimensions of order 200 nm which can swell by
      a factor of at least five, depending on the radiative dose. With the focused
      electron beam, high-density arrays of such nanohydrogels can be flexibly
      patterned onto silicon surfaces. Significantly, the amine groups remain
      functional after e-beam exposure, and we show that they can be used to covalently
      bind proteins and other molecules. We use bovine serum albumin to amplify the
      number of amine groups, and we further demonstrate that different proteins can be
      covalently bound to different hydrogel pads on the same substrate to create
      multifunctional surfaces useful in emerging bio/proteomic and sensor
      technologies.

PMID- 15568867
TI  - Incorporation of Na(+),K(+)-ATP-ase into the thiolipid biomimetic assemblies via
      the fusion of proteoliposomes.
AB  - The black lipid membranes (BLMs) are artificial membrane systems that have been
      widely used in the study of different biological processes. In this paper the
      planar bilayer lipid membranes have been used to study the behavior of thiolipid
      molecules-dipalmitoyl-phosphatidyl-ethanolamine-mercaptopropionamide (DPPE-MPA)
      and cholesteryl 3-mercaptopropionate (Chs-MPA)-as compared to classical BLM made
      of natural lipids. We present our experiments on black thiolipid bilayer (BTM)
      formation from a thiolipid solution and basic results of pump currents generated
      by sodium-potassium pump-Na(+),K(+)-ATP-ase-introduced to such bilayer systems
      via proteoliposome adsorption with subsequent fusion. Our results imply that no
      substantial difference exists between BLMs formed from classical lipids and those
      made from thiolipids used in this study. The same thiolipid molecules were
      subsequently used for the formation of covalently bound, tethered bilayer lipid
      membranes (t-BLMs) on polycrystalline gold electrodes. Similarly, as in the case
      of BLMs, we took advantage of proteoliposome adsorption/fusion to obtain a t-BLM
      system with reconstituted enzyme. The vesicle fusion on hydrophobic or
      hydrophilic substrates is one of the main ways to obtain a bilayer system with
      incorporated biological species. In this paper we present also our preliminary
      results of electrochemical experiments using rapid solution exchange technique on
      such t-BLMs systems and their comparison with painted solid supported membranes
      (SSMs) and BLMs. We have also followed the process of vesicles fusion onto
      thiolipid monolayer by means of in situ atomic force microscopy in tapping mode
      (TM-AFM). On the basis of these experiments, we conclude that DPPE-MPA and Chs
      MPA molecules used in our experiments preserve lipid properties, allowing for at
      least partial reconstitution of Na(+),K(+)-ATP-ase into such t-BLMs. On the other
      hand, the relatively compact organization on polycrystalline gold and the
      hydrophobic nature of the first monolayer of tethered thiolipids slows down the
      proteoliposome fusion onto such monolayers and consequently hinders the protein
      insertion. However, this effect can be overcome by mechanical stimulus that
      facilitates proteoliposome delamination onto the self-assembled monolayer.

PMID- 15568868
TI  - Characterization of single- and double-stranded DNA on gold surfaces.
AB  - Single- and double-stranded deoxy ribonucleic acid (DNA) molecules attached to
      self-assembled monolayers (SAMs) on gold surfaces were characterized by a number
      of optical and electronic spectroscopic techniques. The DNA-modified gold
      surfaces were prepared through the self-assembly of 6-mercapto-1-hexanol and 5'
      C(6)H(12)SH -modified single-stranded DNA (ssDNA). Upon hybridization of the
      surface-bound probe ssDNA with its complimentary target, formation of double
      stranded DNA (dsDNA) on the gold surface is observed and in a competing process,
      probe ssDNA is desorbed from the gold surface. The competition between
      hybridization of ssDNA with its complimentary target and ssDNA probe desorption
      from the gold surface has been investigated in this paper using X-ray
      photoelectron spectroscopy, chronocoulometry, fluorescence, and polarization
      modulation-infrared reflection absorption spectroscopy (PM-IRRAS). The formation
      of dsDNA on the surface was identified by PM-IRRAS by a dsDNA IR signature at
      approximately 1678 cm(-)(1) that was confirmed by density functional theory
      calculations of the nucleotides and the nucleotides' base pairs. The presence of
      dsDNA through the specific DNA hybridization was additionally confirmed by atomic
      force microscopy through colloidal gold nanoparticle labeling of the target
      ssDNA. Using these methods, strand loss was observed even for DNA hybridization
      performed at 25 degrees C for the DNA monolayers studied here consisting of
      attachment to the gold surfaces by single Au-S bonds. This finding has
      significant consequence for the application of SAM technology in the detection of
      oligonucleotide hybridization on gold surfaces.

PMID- 15568869
TI  - Analysis of micro-contact printed protein patterns by SPR imaging with a LED
      light source.
AB  - We demonstrate the characterization of mu-contact printed protein patterns and
      analysis of protein-protein interactions by two-dimensional (2-D) surface plasmon
      resonance imaging (SPRi). Advancements in SPRi image quality from employing a
      light emitting diode (LED) as the light source are described. We show that a LED
      offers an ideal point source that can eliminate interference artifacts and
      speckles found when using a laser source. The attainable thickness resolution in
      fixed-angle imaging is comparable to that of a monochromatic source, providing a
      solid foundation for quantitative analysis with the system. The SPR imaging
      technique reported here affords sub-nanometer thickness sensitivity and
      micrometer lateral resolution, allowing for convenient studies of biomolecular
      interactions and surface morphologies of ultrathin films. Spatially well-defined
      protein patterns of bacterial toxins were obtained by microcontact printing using
      a polydimethylsiloxane (PDMS) stamp on a functionalized self-assembled monolayer
      on Au. The influence of protein concentration in the inking solution on transfer
      efficiency was investigated, and a nonlinear correlation was observed between the
      solution concentration and the amount of protein immobilized on the surface.
      Quantitative analysis of protein interaction was performed with toxin-specific
      antibody, showing a concentration-dependent relationship that verifies the
      retention of biological activity of the protein after printing. The study
      demonstrates the feasibility and effectiveness of using LEDs as light sources in
      SPR imaging, opening doors for developing compact SPR instruments for direct,
      sensitive, and label-free detection of biohazardous molecules.

PMID- 15568870
TI  - Effects of overlapping GB virus C/hepatitis G virus synthetic peptides on
      biomembrane models.
AB  - The present study was undertaken to examine the physicochemical properties of
      three overlapping peptides belonging to the E2 envelope protein of Hepatitis G
      virus (GBV-C/HGV) and its interaction with phospholipid biomembrane models using
      biophysical techniques. We describe our findings concerning the surface activity
      and the interaction of the peptides with monolayers and liposomes composed of the
      zwitterionic phospholipids dipalmitoylphosphatidylcholine and
      dimyristoylphosphatidylcholine (DMPC) and a mixture of DMPC with the anionic
      phospholipid dimyristoylphosphatidylglycerol. The results inform about the effect
      of the chain length on their interaction with biomembrane models. The longest
      chain peptide interacts in a higher extent with all the phospholipid studied as a
      result of a combination of hydrophobic and electrostatic forces.

PMID- 15568871
TI  - Effect of reaction media on the growth and photoluminescence of colloidal CdSe
      nanocrystals.
AB  - Using cadium oxide (CdO) as the Cd precursor and tri-n-octylphosphine selenide
      (TOPSe) as the Se source, TOP-capped and TOP/tri-n-octylphosphine oxide (TOPO)
      capped CdSe nanocrystals were synthesized without the use of an acid. The
      synthetic approach involved the addition of a TOPSe/TOP solution into a CdO/TOP
      solution with or without TOPO at one temperature and subsequent growth at a lower
      temperature. The temporal evolution of the optical properties, namely, absorption
      and luminescence, of the growing nanocrystals was monitored in detail. A
      comprehensive examination on the control of the photoluminescence (PL) properties
      was performed by systematically varying the TOP/TOPO weight ratio of the reaction
      media. Surprisingly, a rational choice of 100% TOP or 80% TOP was found to
      produce "quality" nanocrystals when monitored under the present experimental
      conditions and growth-time scale. The term "quality" is mainly based on the sharp
      features and rich substructure exhibited in the absorption spectra of the growing
      nanocrystals, as well as the sharp features in the emission spectra with narrow
      full width at half-maximum (fwhm). There are two distinguishable stages of
      growth: an early stage (<5 min) and a later stage. TOP plays a major role in the
      control of a slow growth rate in the early stage, while TOPO controls slow growth
      in the later stage. The optical sensitivity of the growing nanocrystals when
      dispersed in nonpolar or polar solvents was studied, including two size-dependent
      parameters, namely, the solvent sensitivity (PL intensity) and nonresonant Stokes
      shift (NRSS). The insights gained from the present study enable a synthetic
      approach in which high-quality CdSe nanocrystals are achieved with high synthetic
      reproducibility.

PMID- 15568872
TI  - Synthesis, surface modification, and multilayer construction of mixed-monolayer
      protected CdS nanoparticles.
AB  - Herein, we describe a study aimed at synthesizing mixed-monolayer-protected CdS
      nanoparticles and investigating the reactivity of surface-bound functional groups
      in order to facilitate the immobilization of nanoparticles on a solid substrate
      as well as the construction of a three-dimensional nanocomposite. CdS
      nanoparticles initially prepared by the reverse micelle method were used to
      modify nanoparticle surfaces with 1-decanethiol molecules by ligand exchange.
      Subsequently, 11-mercapto-1-undecanol was partially incorporated by a place
      exchange reaction, thereby providing stable, mixed-monolayer-protected CdS
      nanoparticles. The nanoparticles obtained at each step were characterized by FT
      IR and UV-vis spectroscopy, transmission electron microscopy, and elemental
      analysis. The reactivity of surface hydroxyl groups was verified by a reaction
      with isocyanate-bearing molecules that provide carbamate bonds in high yields at
      ambient temperature. The obtained mixed-monolayer-protected nanoparticles were
      also successfully immobilized on a glass substrate through a carbamate-bond
      forming reaction that could be further utilized for multilayer construction in a
      layer-by-layer fashion.

PMID- 15568873
TI  - Giant lipid vesicles impaled with glass microelectrodes: GigaOhm seal by membrane
      spreading.
AB  - Giant unilamellar lipid vesicles could be perfect systems to study ion channels
      in the environment of lipid membranes with defined chemical and physical
      properties. Prerequisite for electrical measurements is an intravesicular
      electrical contact. We describe the impalement of giant lipid vesicles by glass
      micropipet electrodes with a tight seal. To avoid displacement or burst during
      impalement, the vesicles are immobilized in relaxed conditions by microscopic
      picket fences of polyimide. The outer surface of the pipets is selectively coated
      with silanes or polylysine. Structurally, the impalement is verified by ejecting
      a fluorescent solution out of the pipet. For electrical characterization, current
      pulses are applied to the pipet and voltage transients are recorded. The data are
      evaluated in terms of the capacitance and effective resistance of the membrane.
      Directly after impalement, we observe a seal resistance up to 1.2 GOmega that
      continuously decays within a period of up to 20 min until it suddenly disappears
      without burst of the vesicle. During impalement, a spreading of the vesicle
      membrane along the outer surface of the pipets is observed using a fluorescent
      membrane-bound dye. We assign the tight pipet-vesicle contact to spreading of the
      lipid bilayer by a rolling mechanism and the loss of resistance to micro- and
      macropores that are induced by the resulting membrane tension. Limitation of
      spreading is attempted with barriers on the pipet.

PMID- 15568874
TI  - Nanostructuring effect of plasma and solvent treatment on polystyrene.
AB  - Plasma treatment of polymer surfaces is used to control the generation of
      topological surface structures: stripes, starlike morphologies, and pinnacles in
      the range from 100 nm up to several micrometers. These protrusions arise when the
      plasma-treated polymer surface is exposed to an organic solvent (liquid or vapor
      phase). The distribution density and the height of the observed structures on the
      surface are functions of the power density of the plasma reactor and the exposure
      time to the plasma, the duration of the development process, the type of the
      polymer, and its manufacturing. We suggest that the structures are generated by
      selective swelling of less cross-linked areas within the polymer surface and not
      by rearrangement or dissolution of polymer chain fragments created by plasma, or
      by amphiphilic moieties due to oxidation as a consequence of plasma treatment.

PMID- 15568875
TI  - Hard structured particles: suspension synthesis, characterization, and
      compressibility.
AB  - Hard interactions are developed on three grades of fumed silica by eliminating
      interparticle forces and sterically stabilizing the particles by attaching an
      organic coating to the surface of the particles, suspending them in an index
      matching solvent and screening the electrostatics. These hard-structured
      particles are studied to understand the effects of the particle's microstructure
      on suspension properties without the influence of interparticle forces other than
      volume exclusion, Brownian, and hydrodynamic interactions. Light and X-ray
      scattering studies of low-volume-fraction suspensions suggest that the fumed
      silicas consist of primary particle of radius of gyration R(g1) approximately
      equals 16 nm and aggregate size R(g2) approximately 50 nm and mass fractal
      dimension D(f) approximately equals 2.2. Osmotic compressibilities of these
      suspensions are measured as a function of particle concentration exploring the
      packing mechanism of fumed silica. While there is minimal detectable change in
      the primary particle size, R(g2) varies by approximately 15%, providing insight
      into how suspension properties are related to particle size. As expected of hard
      particles with the same microstructure, the concentration dependence on the
      osmotic pressure superimposes with volume fraction of solids. The comparison of
      fumed-silica-suspension measurements to the known behavior of hard-sphere
      suspensions demonstrates the effects of particle geometry on suspension
      properties with indications of interpenetration of the fumed silica due to their
      open geometry.

PMID- 15568876
TI  - Synthesis of monodisperse high-aspect-ratio colloidal silicon and silica rods.
AB  - We describe the synthesis and the physical properties of suspensions of colloidal
      silicon and silica rodlike particles. In addition to pure silicon and pure silica
      rods, we have also synthesized silicon rods with a silica shell and silica rods
      with a fluorescent silica layer. Pre-patterned p-type (100) silicon wafers were
      electrochemically etched in electrolyte solutions containing hydrogen fluoride.
      By the current density being varied while etching, macropores were etched with
      controllable modulated pore diameters. These silicon structures were transformed
      into rods with indentations 5.5 mum apart and with lengths up to 100 mum using
      iterative oxidation in air and dissolution of the silica by HF. Complete
      oxidation of these rods was also achieved. Sonication of the modulated rods
      resulted in monodisperse particles of 5.5 mum length and 300 nm width. A high
      yield of 10(12) particles, or more, is possible with this method. At high
      concentrations, these particles show nematic ordering in charge-stabilized
      suspensions. The oxidized silica outer layer of the silicon rods makes the
      further growth of silica in solution or on a wafer possible. This allows for
      control of the particles' interaction potential. Labeling with a fluorescent dye
      and index matching of the complete silica rods enable the study of concentrated
      dispersions quantitatively, on a single particle level, with confocal microscopy.
      Because of their high refractive index in the near-IR, the nematic phases of rods
      with a silica core are also interesting for photonic applications.

PMID- 15568877
TI  - Fabrication of large-area ferromagnetic arrays using etched nanosphere
      lithography.
AB  - Nanosphere lithography (NSL) is a simple, cost-effective, and powerful technique
      capable of producing large-area arrays of ferromagnetic nanostructures with
      dimensions below 100 nm. These properties make NSL an attractive process for the
      fabrication of arrays of magnetic elements with applications in magnetic data
      storage. The main disadvantage with conventional NSL is that the monolayer of
      spheres always contains imperfections that are transferred to the resulting
      nanostructures. This can significantly affect the structural and magnetic
      properties of the fabricated array. In this paper we present a novel adaptation
      of NSL that reduces the effect of such defects on the resulting nanostructures.
      The technique also offers excellent control over the diameter, aspect ratio, and
      pitch of the fabricated elements. These properties are demonstrated through the
      fabrication of arrays of Ni elements of 210 nm diameter and arrays of Co elements
      with diameters between 200 and 320 nm.

PMID- 15568878
TI  - Synthesis of NiGa layered double hydroxides. A combined EXAFS, SAXS, and TEM
      study. 3. Synthesis at constant pH.
AB  - The present paper focuses on the direct synthesis of NiGa layered double
      hydroxides (LDHs) by concomitant addition of Ni and Ga chloride in solution with
      NaOH solution, at a constant pH value of 6.5. Various Ni/Ga ratios (Ni/Ga = 2,
      Ni/Ga = 4, or Ni/Ga = 6) were investigated, and samples were collected after
      successive additions. Each sample was then analyzed by small-angle X-ray
      scattering (SAXS) to derive information about the shape of the objects formed
      upon synthesis. In parallel Ni K-edge and Ga K-edge extended X-ray absorption
      fine structure (EXAFS) analysis were carried out on relevant samples to obtain
      information on the local structure of the species in suspension. SAXS curves
      reveal significant changes. At the beginning of the synthesis, for low added
      volumes (V(s)), the suspension appears to contain both monodimensional and
      bidimensional objects. For higher V(s), the monodimensional objects disappear and
      only platelike particles are detected in the suspension. EXAFS results show that
      all the added gallium atoms are involved in a solid Ni-Ga LDH phase throughout
      the whole synthesis. In contrast, some nickel cations do not precipitate in the
      Ni-Ga LDH. At the beginning of the synthesis, for low added volumes they are also
      involved in the formation of fibrous polycations. For higher added volumes, the
      fibers are not observed anymore and monomeric nickel species are then present in
      the suspension.

PMID- 15568879
TI  - Microemulsion-based synthesis of CeO(2) powders with high surface area and high
      temperature stabilities.
AB  - Pure ceria powders, CeO(2), were synthesized in heptane-microemulsified aqueous
      solutions of CeCl(3) or Ce(NO(3))(3) stabilized by AOT (sodium bis(2-ethylhexyl)
      sulfosuccinate), DDAB (di-n-didodecyldimethylammonium bromide), or DDAB + Brij 35
      surfactant mixtures. Micellar DTAB (n-dodecyltrimethylammonium bromide) and
      vesicular DDAB systems were also used as media for generating CeO(2).
      Characterization of the powders by X-ray powder diffractometry, laser-Raman
      spectroscopy, and Fourier transform infrared spectroscopy revealed that in the
      presence of surfactants almost-agglomerate-free nanosized crystallites (6-13 nm)
      of anionic vacancy-free cubic CeO(2) were produced. In the absence of surfactants
      21-nm-sized crystallites were formed, comparing with the 85-nm-sized crystallites
      when cubic CeO(2) was created via thermal decomposition of cerium oxalate.
      Surface characterization, by X-ray photoelectron spectroscopy, N(2) sorptiometry,
      and high-resolution electron microscopy showed AOT- or (DDAB + Brij 35)
      stabilized microemulsions to assist in formation of crystallites exposing
      surfaces of large specific areas (up to ca. 250 m(2)/g) but of low stability to
      high-temperature calcination (28-13 m(2)/g at 800 degrees C). In contrast, the
      double-chained DDAB was found to generate cubic CeO(2) crystallites of lower
      initial surface areas (144 (microemulsion) to 125 (vesicles) m(2)/g)) but of
      higher thermal stability (55-45 m(2)/g at 800 degrees C). Hence, the latter
      cerias could be considered as appropriate components for total oxidation
      (combustion) catalysts.

PMID- 15568880
TI  - Novel CuS nanofibers using organogel as a template: controlled by binding sites.
AB  - A new cholesterol organogelator 1 was synthesized, which was confirmed as an
      effective gelator for various organic solvents and could self-assemble into
      network fibers in some organic solvents. Moreover, gelator 1 could act as
      templates for the synthesis of various CuS nanofibers with different helical
      pitches. For example, when H(2)S was used as the sulfur source, straight and
      bending helical CuS nanofibers with a pitch of 100-200 nm could be fabricated in
      butyl acetate and benzene-butanol gel systems, respectively, while bending CuS
      nanofibers with a similar helical pitch (ca. 50 nm) could be obtained when
      thioacetamide was used as the sulfur source in both gel systems. It was first
      found that the morphologies of inorganic nanofibers could be controlled by the
      binding sites between the inorganic precursor and the organogel.

PMID- 15568881
TI  - Composition-controlled synthesis of bimetallic gold-silver nanoparticles.
AB  - This paper reports findings of an investigation of the synthesis of monolayer
      capped binary gold-silver (AuAg) bimetallic nanoparticles that is aimed at
      understanding the control factors governing the formation of the bimetallic
      compositions. The synthesis of alkanethiolate-capped AuAg nanoparticles was
      carried out using two related synthetic protocols using aqueous sodium
      borohydride as a reducing agent. One involves a two-phase reduction of AuCl(4)(
      ), which is dissolved in organic solution, and Ag(+), which is dissolved in
      aqueous solution. The other protocol involves a two-phase reduction of AuCl(4)(-)
      and AgBr(2)(-), both of which are dissolved in the same organic solution. AuAg
      nanoparticles of 2-3 nm core sizes with different compositions in the range of 0
      100% Au have been synthesized. The two synthetic routes were compared in terms of
      bimetallic composition and size properties. Our new findings have allowed us to
      establish the correlation between synthetic feeding of metals and metal
      compositions in the bimetallic nanoparticles, which have important implications
      to the exploration of gold-based bimetallic nanoparticles for constructing
      sensing and catalytic nanomaterials.

PMID- 15568882
TI  - Probing the effects of interfacial chemistry on the kinetics of phase transitions
      in amorphous and tetragonal zirconia nanocrystals.
AB  - In this work, we examine the phase stability of both uncoated and alumina-coated
      zirconia nanoparticles using in-situ X-ray diffraction. By tracking structural
      changes in these particles, we seek to understand how changing interfacial
      bonding affects the kinetics of amorphous zirconia crystallization and the
      kinetics of grain growth in both initially amorphous and initially crystalline
      zirconia nanocrystals. Activation energies associated with crystallization are
      calculated using nonisothermal kinetic methods. The crystallization of the
      uncoated amorphous zirconia colloids has an activation energy of 117 +/- 13
      kJ/mol, while that for the alumina-coated amorphous colloids is 185 +/- 28
      kJ/mol. This increase in activation energy is attributed to inhibition of atomic
      rearrangement imparted by the alumina coating. The kinetics of grain growth are
      also studied with nonisothermal kinetic methods. The alumina coating again
      dramatically affects the activation energies. For colloids that were coated with
      alumina when they were in an amorphous structure, the coating imparts a 5x
      increase in the activation energy for grain growth (33 +/- 8 versus 150 +/- 30
      kJ/mol). This increase shows that the alumina coating inhibits zirconia cores
      from coarsening. When the colloids are synthesized in the tetragonal phase and
      then coated with alumina, the effect of surface coating on coarsening kinetics is
      even more dramatic. In this case, a 10x increase in activation energies, from 28
      +/- 3 kJ/mol for the uncoated particles to 300 +/- 25 kJ/mol for the alumina
      coated crystallites, is found. The results show that one can alter phase
      stability in colloidal systems by using surface coatings and interfacial energy
      to dramatically change the kinetic barriers to structural rearrangement.

PMID- 15568883
TI  - (1)H NMR and small-angle neutron scattering investigation of the structure and
      solubilization behavior of three-layer nanoparticles.
AB  - Three-layer nanoparticles were prepared by radiation-induced polymerization of 1
      10 g/L of methyl methacrylate dissolved in a 0.1 wt % D(2)O solution of
      polystyrene-poly(methacrylic acid) (PS-PMA) micelles. According to NMR and small
      angle neutron scattering (SANS), most of the poly(methyl methacrylate) (PMMA) is
      adsorbed at the core-shell interface of the particles. A small fraction of
      shorter PMMA probably sticks to outer parts of the PMA chains. The absorption
      kinetics and equilibria of benzene and chloroform were studied by NMR and SANS
      time-resolved experiments. The diffusion front in the PS core is very narrow but
      quite broad in the PMMA sheet suggesting, thus, a less compact state of PMMA.
      According to SANS, the diffusion kinetics is almost independent of the PMMA sheet
      thickness. In contrast to it, the absorption capacity, reflected by both SANS and
      NMR, increases markedly with the PMMA content in the particle. The maximum amount
      of solubilized compound depends on its positive interaction with PMMA (expressed
      by the chi parameter) but is restricted by the growing interface tension between
      swollen PMMA and D(2)O. In accordance with this conclusion, a particle saturated
      with benzene can absorb chloroform only at the expense of a part of benzene
      expelled into the surrounding medium and vice versa. Starting with 10 g PMMA/L
      (10 times the weight of the original micelles), the particles become unstable
      when being swollen with a good solvent.

PMID- 15568884
TI  - Engineering the chemistry and nanostructure of porous silicon Fabry-Perot films
      for loading and release of a steroid.
AB  - A method for engineering the surface chemistry and pore dimensions in porous Si
      films for the purpose of controlling the loading and release of a hydrophobic
      drug is described. Loading of the steroid dexamethasone is confirmed by Fourier
      transform infrared spectroscopy, and the release rates are characterized by
      observation of the appearance of the drug in solution (UV-vis absorption
      spectroscopy) and by measurement of the Fabry-Perot fringes in the optical
      reflectivity spectrum of the porous Si film. Optical reflectivity changes provide
      a measure of the release rate of the drug that is amenable to in-vivo diagnostic
      applications. Fresh porous Si films are prepared by electrochemical etch and
      subsequently modified by hydrosilylation with 1-dodecene. The dodecene-modified
      samples are more robust in aqueous environments and exhibit slower release rates
      of the drug relative to freshly etched porous Si. Whereas the relatively large
      dexamethasone molecule is found to infiltrate the freshly etched samples, it does
      not enter the chemically modified films, because of steric crowding from the
      dodecyl species. To achieve a high degree of loading into these modified films,
      the pores are enlarged before hydrosilylation by treatment with an aqueous
      solution containing HF and dimethyl sulfoxide. The pore expanded, chemically
      modified samples admit approximately 70% of the dexamethasone that can be
      admitted into an unmodified (freshly etched) sample. Diffusion of the steroid
      from the modified, pore expanded films into phosphate-buffered saline solution is
      slower than from the unmodified sample by a factor of approximately 20, with 90%
      of the drug delivered in 3 days for the chemically modified films compared to 3 h
      for the unmodified films.

PMID- 15568885
TI  - Effect of ionic size on the deposition of charge-regulated particles to a charged
      surface.
AB  - The deposition of charge-regulated particles to a rigid, planar charged surface
      is modeled theoretically, taking the effects of the excluded area arising from
      deposited particles and finite ionic sizes into account. Here, a particle
      comprises a rigid core and an ion-penetrable charged membrane layer, which
      represents a general type of particle. If the membrane layer has a negligible
      thickness, the particle simulates a regular inorganic particle, and if the
      membrane layer has a finite thickness, it simulates biocolloids such as cells.
      The results of numerical simulation reveal that the rate of particle deposition
      is faster under the following conditions: (1) lower potential of the planar
      surface, (2) thicker membrane, (3) higher counterion valance, (4) lower fixed
      charge density, (5) smaller counterions, (6) larger co-ions, (7) larger
      functional group, and (8) lower pH. Neglecting the sizes of ionic species may
      lead to an appreciable deviation in both the electrical repulsive force between
      particle and surface and the rate of deposition. Typical deviation for the former
      is approximately 20%, and that for the latter is approximately -75%.

PMID- 15568886
TI  - Theoretical characterization of triangular CdS nanocrystals: a tight-binding
      approach.
AB  - We provide theoretical modeling of the optical spectrum of recently synthesized
      triangular CdS nanocrystals by means of atomistic tight-binding theory. Both zinc
      blende and wurtzite structures are considered. Optical properties predicted for
      triangular prisms are very different from the ones obtained for tetrahedral
      quantum dots when z-polarized light is employed. In particular, the ground
      transition is dim for triangular prisms, whereas it is bright and highly intense
      for tetrahedra. The high sensitivity of the fine optical properties on the
      quantum dot shape allows us to discriminate between truncated tetrahedra and
      triangular prisms and also to estimate the thickness of the nanocrystals.

PMID- 15568888
TI  - Pharmacokinetics of antiretrovirals in pregnant women.
AB  - Antiretroviral treatment of HIV-infected pregnant women is widely used to prevent
      mother-to-child HIV transmission and as primary therapy of maternal HIV
      infection. The physiological changes associated with pregnancy have a large
      impact on drug disposition, and changes in antiretroviral pharmacokinetics during
      pregnancy must be understood for these drugs to be used safely and effectively in
      pregnant women. Zidovudine and didanosine, two of the nucleoside reverse
      transcriptase inhibitors, demonstrate an increase in clearance and decrease in
      area under the concentration-time curve during pregnancy. The clinical
      significance of these changes is unknown due to the lack of a clear relationship
      between plasma concentrations of nucleoside reverse transcriptase inhibitors and
      clinical effects. Pharmacokinetic parameters of lamivudine, stavudine and
      abacavir are not significantly changed during pregnancy. There are no data
      describing the effect of pregnancy on the pharmacokinetics of the other
      nucleoside/nucleotide analogues (zalcitabine, emtricitabine and tenofovir).
      Pregnancy does not appear to have a significant effect on the pharmacokinetics of
      the non-nucleoside reverse transcriptase inhibitor nevirapine and there are no
      data describing the pharmacokinetics of the other non-nucleoside reverse
      transcriptase inhibitors (efavirenz and delavirdine) during pregnancy. Reduced
      plasma concentrations during pregnancy have been described for several of the
      protease inhibitors, including nelfinavir (with administration of 750 mg three
      times daily), indinavir, saquinavir and Kaletra (a co-formulation of lopinavir
      and ritonavir). Plasma concentrations equivalent to those in nonpregnant adults
      have been reported in pregnant women receiving nelfinavir at doses of 1250 mg
      twice daily, and the addition of ritonavir to saquinavir greatly increases
      saquinavir exposure to therapeutic concentrations in pregnant women. No pregnancy
      pharmacokinetic data are available for the newer protease inhibitors atazanavir
      and fosamprenavir, or with other dual protease inhibitor combinations that
      include low dose ritonavir to boost concentrations of the coadministered protease
      inhibitor. Further investigations of antiretroviral pharmacology during
      pregnancy, including protein binding studies, are urgently needed.

PMID- 15568889
TI  - Clinical pharmacology of bosentan, a dual endothelin receptor antagonist.
AB  - Bosentan, a dual endothelin receptor antagonist, is indicated for the treatment
      of patients with pulmonary arterial hypertension (PAH). Following oral
      administration, bosentan attains peak plasma concentrations after approximately 3
      hours. The absolute bioavailability is about 50%. Food does not exert a
      clinically relevant effect on absorption at the recommended dose of 125 mg.
      Bosentan is approximately 98% bound to albumin and, during multiple-dose
      administration, has a volume of distribution of 30 L and a clearance of 17 L/h.
      The terminal half-life after oral administration is 5.4 hours and is unchanged at
      steady state. Steady-state concentrations are achieved within 3-5 days after
      multiple-dose administration, when plasma concentrations are decreased by about
      50% because of a 2-fold increase in clearance, probably due to induction of
      metabolising enzymes. Bosentan is mainly eliminated from the body by hepatic
      metabolism and subsequent biliary excretion of the metabolites. Three metabolites
      have been identified, formed by cytochrome P450 (CYP) 2C9 and 3A4. The metabolite
      Ro 48-5033 may contribute 20% to the total response following administration of
      bosentan. The pharmacokinetics of bosentan are dose-proportional up to 600 mg
      (single dose) and 500 mg/day (multiple doses). The pharmacokinetics of bosentan
      in paediatric PAH patients are comparable to those in healthy subjects, whereas
      adult PAH patients show a 2-fold increased exposure. Severe renal impairment
      (creatinine clearance 15-30 mL/min) and mild hepatic impairment (Child-Pugh class
      A) do not have a clinically relevant influence on the pharmacokinetics of
      bosentan. No dosage adjustment in adults is required based on sex, age, ethnic
      origin and bodyweight. Bosentan should generally be avoided in patients with
      moderate or severe hepatic impairment and/or elevated liver aminotransferases.
      Ketoconazole approximately doubles the exposure to bosentan because of inhibition
      of CYP3A4. Bosentan decreases exposure to ciclosporin, glibenclamide, simvastatin
      (and beta-hydroxyacid simvastatin) and (R)- and (S)-warfarin by up to 50% because
      of induction of CYP3A4 and/or CYP2C9. Coadministration of ciclosporin and
      bosentan markedly increases initial bosentan trough concentrations. Concomitant
      treatment with glibenclamide and bosentan leads to an increase in the incidence
      of aminotransferase elevations. Therefore, combined use with ciclosporin and
      glibenclamide is contraindicated and not recommended, respectively. The
      possibility of reduced efficacy of CYP2C9 and 3A4 substrates should be considered
      when coadministered with bosentan. No clinically relevant interaction was
      detected with the P-glycoprotein substrate digoxin. In healthy subjects, bosentan
      doses >300 mg increase plasma levels of endothelin-1. The drug moderately reduces
      blood pressure, and its main adverse effects are headache, flushing, increased
      liver aminotransferases, leg oedema and anaemia. In a pharmacokinetic
      pharmacodynamic study in PAH patients, the haemodynamic effects lagged the plasma
      concentrations of bosentan.

PMID- 15568890
TI  - Biowaivers for oral immediate-release products: implications of linear
      pharmacokinetics.
AB  - Bioequivalence of drug formulations plays an important role in drug development.
      Recently, the Biopharmaceutical Classification System (BCS) has been implemented
      for the purpose of waiving bioequivalence studies on the basis of the solubility
      and gastrointestinal permeability of drug substance. Using the rationale of the
      BCS, it can be argued that biowaivers can, however, also be granted on the basis
      of standard pharmacokinetic data. If a drug exhibits dose-linear pharmacokinetics
      and a sufficiently fast dissolution profile, it can be concluded that this drug
      appears to pose no problem with respect to absorption. It should be noted that a
      change of an immediate-release tablet formulation can only lead to a deviating
      rate and/or extent of absorption when release of the drug from the formulation is
      altered. Logically, the dissolution profiles of the different formulations should
      be equal to guarantee bioequivalency. Thus, both BCS and the alternative linear
      pharmacokinetics approach require an evaluation of dissolution profiles. The
      justification of BCS is found in the permeability classification of the compound,
      while those of the linear pharmacokinetics lie in the apparent lack of a
      permeability problem. For example, in this context P-glycoprotein-transported
      drugs form an interesting class of compounds, which may be treated likewise when
      complying to the aforementioned requirements. Furthermore, poorly soluble
      compounds may be less troublesome than expected. It is shown that linear kinetics
      can be explained by the solubilising activity of, for example, bile salts. In
      this instance, linear pharmacokinetics shows that elevated doses do not appear to
      exhibit a limiting role on the dissolution. Hence, a change in formulation
      without any effect on the dissolution profile is not expected to cause a change
      in availability. It is clear that the formulations to be compared should not
      contain excipients that display an effect on (presystemic) drug metabolism.

PMID- 15568892
TI  - Magnitude and time-course of arterio-venous differences in blood-alcohol
      concentration in healthy men.
AB  - BACKGROUND AND OBJECTIVE: Human studies of arterio-venous (AV) differences in
      drug concentrations and the consequences for pharmacokinetic modelling and
      concentration-effect relationships are very limited. We therefore investigated
      the intravenous and intra-arterial concentrations of alcohol (ethanol) during the
      absorption, distribution and elimination stages of alcohol metabolism in healthy
      men. STUDY PARTICIPANTS AND METHODS: Nine male volunteers aged 26-67 years drank
      0.6 g alcohol/kg bodyweight in 2-15 minutes. The drink was prepared from 95% v/v
      alcohol, which was diluted with an alcohol-free beverage to 20% v/v. Before the
      start of drinking and for 6-7 hours post-administration, blood samples were drawn
      at 15- to 20-minute intervals from indwelling catheters in a radial artery and a
      cubital vein on the same arm. The blood-alcohol concentration (BAC) was
      determined by headspace gas chromatography, and blood-water content was measured
      by desiccation. RESULTS: The peak concentration (Cmax) of alcohol in arterial
      blood was 0.98 g/L (SD 0.209) compared with 0.84 g/L (SD 0.176) for venous blood
      (p < 0.001), whereas median time to reach Cmax (tmax) was the same (35 minutes).
      The AV difference was greatest at 10 minutes after the end of drinking (mean 0.20
      g/L [range 0.09-0.40 g/L]), decreasing as the absorption of alcohol continued. At
      a median time of 90 minutes post-administration (range 45-105 minutes), the AV
      difference was momentarily zero. At later times, the AV differences became
      increasingly negative and at 280 minutes post-administration the mean was -0.051
      g/L (range -0.025 to -0.078 g/L). The slope of the post-absorptive phase (k0) was
      0.116 g/L/h (SD 0.0167) for arterial blood compared with 0.109 g/L/h (SD 0.0185)
      for venous blood (p < 0.001). The extrapolated time to reach zero BAC was 391
      minutes (SD 34) for arterial blood and 420 minutes (SD 41) for venous blood; the
      difference of 29 minutes was statistically highly significant (p < 0.001). The
      apparent volume of distribution of alcohol, the area under the concentration-time
      curves (AUC) and the water content of arterial and venous blood samples were not
      significantly different for the two sampling compartments. CONCLUSION: The
      arterial and venous blood-alcohol profiles were shifted in time owing to the time
      it takes for alcohol to equilibrate between arterial blood and tissue water.
      Alcohol is metabolised in the liver but not in muscle tissue, which acts as a
      reservoir for alcohol. The concentrations of alcohol in arterial and venous blood
      were the same at only one timepoint, which signifies complete equilibration of
      alcohol in total body water. During the entire post-absorptive phase, the
      concentration of alcohol in venous blood draining skeletal muscles was slightly
      greater than the arterial blood concentration; therefore, the AV differences were
      negative.

PMID- 15568891
TI  - Effects of food on the clinical pharmacokinetics of anticancer agents: underlying
      mechanisms and implications for oral chemotherapy.
AB  - Pharmacokinetic interactions between food and orally administered drugs involve
      changes mainly in the absorption and metabolism of a drug, and may have clinical
      implications. Such interactions, in particular, may be of major clinical
      significance for cancer chemotherapy since the majority of anticancer agents are
      toxic, have a low therapeutic index and are administered long term, most often in
      combination with other cytotoxic agents. The purpose of this review is to compare
      the pharmacokinetic profiles of various anticancer drugs, including
      chemopreventive agents that have been examined previously in fasted and fed
      conditions, and to discuss the underlying basis/mechanisms of food effect in
      light of a drug's physicochemical and pharmacokinetic properties. Clinical
      pharmacokinetic parameters such as maximum concentration, area under the
      concentration-time curve, time to maximum concentration and half-life for each
      drug are compared in fasted and fed states, and specific dietary recommendations
      are summarised accordingly. In addition, the effects of food on the metabolite
      kinetics and pharmacodynamic responses, and the potential role of food effect in
      the modulation of oral biovariability and multidrug resistance have been
      extensively discussed. Overall, this comprehensive pharmacokinetic analysis
      indicates that a broad spectrum of food effects is seen among anticancer agents
      because of diverse factors regulating each drug's oral bioavailability and its
      interactions with food. The consideration of such effects is important, as it
      could lead to more rational pharmacological monitoring and possibly improve the
      oral chemotherapy of cancer in children, adults and the elderly.

PMID- 15568893
TI  - A standard weight descriptor for dose adjustment in the obese patient.
AB  - OBJECTIVE: To develop a standard weight descriptor that can be used for
      estimation of patient size for obese patients. PATIENTS AND METHODS: Data were
      available from 3849 patients: 2839 from oncology patients (index data set) and
      1010 from general medical patients (validation data set). The patients had a wide
      range of age (16-100 years), weight (25-165 kg) and body mass index (BMI) [12-52
      kg/m2] in both data sets. From the normal-weight patients in the oncology data
      set, an equation for male and female patients was developed to predict their
      normal weight as the sum of the lean body mass and normal fat body mass. The
      equations were evaluated by predicting the weight of patients in the general
      medical data set who had a normal BMI (<25 kg/m2). In addition, the clinical
      utility of the predicted normal weight (PNWT) descriptor was assessed by (i)
      comparing body surface area and allometric scaling calculations based on actual
      weight of obese patients versus PNWT; and (ii) comparing the predictive
      performance of creatinine clearance using the Cockcroft and Gault equation when
      using actual weight of obese patients versus PNWT to predict gentamicin
      clearance. RESULTS: The PNWT equations developed from the oncology data set
      predicted accurately the actual weight of normal weighted (BMI <25 kg/m2) general
      medical patients (R2 = 0.968 men, R2 = 0.946 women). Using actual weight when
      computing body surface area and when allometric scaling for obese patients
      results in significant overestimation of patient size, especially for female
      patients and those with BMIs >35 kg/m2. The use of PNWT in the Cockcroft and
      Gault equation provided better predictions of gentamicin clearance than when
      using actual weight. CONCLUSIONS: A standard weight descriptor has been developed
      that can be used in dosing algorithms for patients who are obese (BMI >30 kg/m2).

PMID- 15568895
TI  - Fractal lifetimes in the transition to turbulence.

PMID- 15568894
TI  - Into the Daphnia vortex.

PMID- 15568896
TI  - Coherent vortices in two-dimensional turbulence.

PMID- 15568897
TI  - Simulating coarsening dynamics of fractal clusters.

PMID- 15568899
TI  - Introduction: first annual gallery of nonlinear images (montreal, quebec, Canada,
      2004).

PMID- 15568898
TI  - Global organization of dynamics in cultured cardiac monolayers.

PMID- 15568900
TI  - Visualizing chiral self-assembly.

PMID- 15568901
TI  - Dynamics of meteor impacts.

PMID- 15568902
TI  - Craze formation and the fracture energy of glassy polymers.

PMID- 15568903
TI  - Transport-limited aggregation.

PMID- 15568904
TI  - Advection-diffusion-limited aggregation.

PMID- 15568905
TI  - Characterizing intense rotation and dissipation in turbulent flows.

PMID- 15568906
TI  - Polymerlike folding of a two-dimensional granular chain in water.

PMID- 15568907
TI  - Efficiency and current in a correlated ratchet.
AB  - We present a detailed study of the transport and the efficiency of a ratchet
      system in a periodic potential in the presence of correlated noises. The current
      and the efficiency of the system are investigated. It is found that, when the
      potential is spatially symmetric, the correlation between the two noises can
      induce a net transport. The efficiency shows many interesting features as a
      function of the applied force, the noise intensity, the external load, etc. The
      efficiency can be maximized as a function of noise intensity (or temperature),
      which shows that the thermal fluctuation can facilitate the efficiency of energy
      transformation.

PMID- 15568908
TI  - Filters display inverse limit spaces.
AB  - A rigorous proof that linear filters display the inverse limit spaces of chaotic
      maps is given.

PMID- 15568909
TI  - Symmetry properties of periodic orbits extracted from scattering data.
AB  - Discrete symmetries of a system are reflected in the properties of the shortest
      periodic orbits. By applying a recent method to extract these from the scaling of
      the fractal structure in scattering functions, we show how the symmetries can be
      extracted from scattering data simultaneously with the periods and the Lyapunov
      exponents. We pay particular attention to the change of scattering data under a
      small symmetry breaking.

PMID- 15568910
TI  - Recurrence time statistics for finite size intervals.
AB  - We investigate the statistics of recurrences to finite size intervals for chaotic
      dynamical systems. We find that the typical distribution presents an exponential
      decay for almost all recurrence times except for a few short times affected by a
      kind of memory effect. We interpret this effect as being related to the unstable
      periodic orbits inside the interval. Although it is restricted to a few short
      times it changes the whole distribution of recurrences. We show that for systems
      with strong mixing properties the exponential decay converges to the Poissonian
      statistics when the width of the interval goes to zero. However, we alert that
      special attention to the size of the interval is required in order to guarantee
      that the short time memory effect is negligible when one is interested in
      numerically or experimentally calculated Poincare recurrence time statistics.

PMID- 15568911
TI  - A fractional equation for anomalous diffusion in a randomly heterogeneous porous
      medium.
AB  - A fractional partial differential equation is derived for the spreading of matter
      in a saturated porous medium starting from precise hypotheses concerning the
      medium itself, which is a collection of intertwisted tubes with randomly
      distributed slopes, filled with quiescent fluid. Examining the fundamental
      solution of the fractional equation indicates that the second moment is not
      proportional to time, which is the signature of anomalous diffusion. The equation
      derived preserves non-negativity and also the total mass of matter.

PMID- 15568912
TI  - Pursuit-evasion predator-prey waves in two spatial dimensions.
AB  - We consider a spatially distributed population dynamics model with excitable
      predator-prey kinetics, where species propagate in space due to their taxis with
      respect to each other's gradient in addition to, or instead of, their diffusive
      spread. Earlier, we have described new phenomena in this model in one spatial
      dimension, not found in analogous systems without taxis: reflecting and self
      splitting waves. Here we identify new phenomena in two spatial dimensions:
      unusual patterns of meander of spirals, partial reflection of waves, swelling
      wave tips, attachment of free wave ends to wave backs, and as a result, a novel
      mechanism of self-supporting complicated spatiotemporal activity, unknown in
      reaction-diffusion population models.

PMID- 15568913
TI  - Bifurcation of synchronous oscillations into torus in a system of two
      reciprocally inhibitory silicon neurons: experimental observation and modeling.
AB  - Oscillatory activity in the central nervous system is associated with various
      functions, like motor control, memory formation, binding, and attention.
      Quasiperiodic oscillations are rarely discussed in the neurophysiological
      literature yet they may play a role in the nervous system both during normal
      function and disease. Here we use a physical system and a model to explore
      scenarios for how quasiperiodic oscillations might arise in neuronal networks. An
      oscillatory system of two mutually inhibitory neuronal units is a ubiquitous
      network module found in nervous systems and is called a half-center oscillator.
      Previously we created a half-center oscillator of two identical oscillatory
      silicon (analog Very Large Scale Integration) neurons and developed a
      mathematical model describing its dynamics. In the mathematical model, we have
      shown that an in-phase limit cycle becomes unstable through a subcritical torus
      bifurcation. However, the existence of this torus bifurcation in experimental
      silicon two-neuron system was not rigorously demonstrated or investigated. Here
      we demonstrate the torus predicted by the model for the silicon implementation of
      a half-center oscillator using complex time series analysis, including
      bifurcation diagrams, mapping techniques, correlation functions, amplitude
      spectra, and correlation dimensions, and we investigate how the properties of the
      quasiperiodic oscillations depend on the strengths of coupling between the
      silicon neurons. The potential advantages and disadvantages of quasiperiodic
      oscillations (torus) for biological neural systems and artificial neural networks
      are discussed.

PMID- 15568914
TI  - A practical method to experimentally evaluate the Hausdorff dimension: an
      alternative phase-transition-based methodology.
AB  - We introduce a methodology to estimate numerically the Hausdorff dimension of a
      geometric set. This practical method has been conceived as a subsequent tool of
      another context study, associated to our concern to distinguish between various
      fractal sets. Its conception is natural since it can be related to the original
      idea involved in the definitions of Hausdorff measure and Hausdorff dimension. It
      is based on the critical behavior of the measure spectrum functions of the set
      around its Hausdorff dimension value. We illustrate on several well-known
      examples, the ability of this method to accurately estimate the Hausdorff
      dimension. Also, we show how the transition property, exhibited by the quantities
      used as substitutes of the Hausdorff measure in the corresponding fractal
      dimension relationships, can be used to accurately estimate the fractal
      dimension. To show the potential of our method, we also report the results of
      Hausdorff dimension measurements on some typical examples, compared to a direct
      application of the scaling relation involved in the box-counting dimension
      definition.

PMID- 15568915
TI  - Phase synchronization in unidirectionally coupled chaotic ratchets.
AB  - We study chaotic phase synchronization of unidirectionally coupled deterministic
      chaotic ratchets. The coupled ratchets were simulated in their chaotic states and
      perfect phase locking was observed as the coupling was gradually increased. We
      identified the region of phase synchronization for the ratchets and show that the
      transition to chaotic phase synchronization is via an interior crisis transition
      to strange attractor in the phase space.

PMID- 15568916
TI  - On the control of chaotic systems via symbolic time series analysis.
AB  - Symbolic analysis of time series is extended to systems with inputs, in order to
      obtain input/output symbolic models to be used for control policy design. For
      that, the notion of symbolic word is broadened to possibly include past input
      values. Then, a model is derived in the form of a controlled Markov chain, i.e.,
      transition probabilities are conditioned on the control value. The quality of
      alternative models with different word length and alphabet size is assessed by
      means of an indicator based on Shannon entropy. A control problem is formulated,
      with the goal of confining the system output in a smaller domain with respect to
      that of the uncontrolled case. Solving this problem (by means of a suitable
      numerical method) yields the relevant control policy, as well as an estimate of
      the probability distribution of the output of the controlled system. Three
      examples of application (based on the analysis of time series synthetically
      generated by the logistic map, the Lorenz system, and an epidemiological model)
      are presented and used to discuss the features and limitations of the method.

PMID- 15568917
TI  - Experimental observation of delay-induced radio frequency chaos in a transmission
      line oscillator.
AB  - We report an experimental study of fast chaotic dynamics in a delay dynamical
      system. The system is an electronic device consisting of a length of coaxial
      cable terminated on one end with a diode and on the other with a negative
      resistor. When the negative resistance is large, the system evolves to a steady
      state. As the negative resistance is decreased, a Hopf bifurcation occurs. By
      varying the length of the transmission line we observe Hopf frequencies from 7-53
      MHz. With the transmission line length fixed, we observe a period doubling route
      to chaos as the negative resistance is further reduced providing the first
      experimental confirmation of an existing theoretical model for nonlinear dynamics
      in transmission line oscillators [Corti et al., IEEE Trans. Circ. Syst., I:
      Fundam. Theory Appl. 41, 730 (1994)]. However, other experimental results
      indicate limitations to this model including an inability to predict the Hopf
      frequency or to produce realistic continuous wave forms. We extend the model to
      include finite bandwidth effects present in a real negative resistor. The
      resulting model is a neutral delay differential equation that provides better
      agreement with experimental results.

PMID- 15568918
TI  - Localized error bursts in estimating the state of spatiotemporal chaos.
AB  - We consider the problem of estimating the current state of an evolving
      spatiotemporally chaotic system from noisy observations of the system state and a
      model of the system dynamics. Using a simple scheme for state estimation, we show
      the possible occurrence of temporally and spatially intermittent large bursts in
      the estimation error. We discuss the similarity of these bursts with those
      occurring at the bubbling transition in the synchronization of low dimensional
      chaotic dynamical systems. We characterize the spatial and temporal behavior of
      the bursts and investigate how the behavior changes as we vary the number and
      location of the observations.

PMID- 15568919
TI  - Estimation of initial conditions and parameters of a chaotic evolution process
      from a short time series.
AB  - Tracing back to the initial state of a time-evolutionary process using a segment
      of historical time series may lead to many meaningful applications. In this
      paper, we present an estimation method that can detect the initial conditions,
      unobserved time-varying states and parameters of a dynamical (chaotic) system
      using a short scalar time series that may be contaminated by noise. The technique
      based on the Newton-Raphson method and the least-squares algorithm is tolerant to
      large mismatch between the initial guess and actual values. The feasibility and
      robustness of this method are illustrated via the numerical examples based on the
      Lorenz system and Rossler system corrupted with Gaussian noise.

PMID- 15568920
TI  - Chaotic behavior of a Galerkin model of a two-dimensional flow.
AB  - Chaotic behavior of a Galerkin model of the Kolmogorov fluid motion equations is
      demonstrated. The study focuses on the dynamical behavior of limit trajectories
      branching off secondary periodic solutions. It is shown that four limit
      trajectories exist and transform simultaneously from periodic solutions to
      chaotic attractors through a sequence of bifurcations including a periodic
      doubling scenario. Some instability regimes display close similarities to those
      of a discrete dynamical system generated by an interval map.

PMID- 15568921
TI  - Global dynamics of low immersion high-speed milling.
AB  - In the case of low immersion high-speed milling, the ratio of time spent cutting
      to not cutting can be considered as a small parameter. In this case the classical
      regenerative vibration model of machine tool vibrations reduces to a simplified
      discrete mathematical model. The corresponding stability charts contain stability
      boundaries related to period doubling and Neimark-Sacker bifurcations. The
      subcriticality of both types of bifurcations is proved in this paper. Further,
      global period-2 orbits are found and analyzed. In connection with these orbits,
      the existence of chaotic motion is demonstrated for realistic high-speed milling
      parameters.

PMID- 15568922
TI  - Public-key encryption with chaos.
AB  - We propose public-key encryption algorithms based on chaotic maps, which are
      generalization of well-known and commercially used algorithms: Rivest-Shamir
      Adleman (RSA), ElGamal, and Rabin. For the case of generalized RSA algorithm we
      discuss in detail its software implementation and properties. We show that our
      algorithm is as secure as RSA algorithm.

PMID- 15568923
TI  - Food chain chaos with canard explosion.
AB  - The "tea-cup" attractor of a classical prey-predator-superpredator food chain
      model is studied analytically. Under the assumption that each species has its own
      time scale, ranging from fast for the prey to intermediate for the predator and
      to slow for the superpredator, the model is transformed into a singular perturbed
      system. It is demonstrated that the singular limit of the attractor contains a
      canard singularity. Singular return maps are constructed for which some
      subdynamics are shown to be equivalent to chaotic shift maps. Parameter regions
      in which the described chaotic dynamics exist are explicitly given.

PMID- 15568924
TI  - Regularization of the collision in the electromagnetic two-body problem.
AB  - We derive a differential equation that is regular at the collision of two equal
      mass bodies with attractive interaction in the relativistic action-at-a-distance
      electrodynamics. We use the energy constant related to the Poincare invariance of
      the theory to define finite variables with finite derivatives at the collision.
      The collision orbits are calculated numerically using the regular equation
      adapted in a self-consistent minimization method (a stable numerical method that
      chooses only nonrunaway solutions). This dynamical system appeared 100 years ago
      as an example of covariant time-symmetric two-body dynamics and acquired the
      status of electrodynamics in the 1940s by the works of Dirac, Wheeler, and
      Feynman. We outline the method with an emphasis on the physics of this complex
      conservative dynamical system.

PMID- 15568925
TI  - Equilibrium bifurcations and chaotic transitions in coupled microlaser lattices.
AB  - Analytic and simulation studies for the steady-state equilibria and bifurcations
      of coupled microlaser arrays are described. Lateral cavity interactions affect
      the gain in each cavity, leading to active photonic lattice behavior, equivalent
      to a nonlinear coupled oscillator lattice. The coupled-cavity rate equations are
      employed to follow the coherent photon and carrier population in each lattice
      site. Fixed-point-type steady states, of constant lattice phase shift, result for
      low coupling strengths; the radiation envelope for these states conforms with a
      periodic Bloch state over the array. Bifurcations to limit cycles of increasing
      complexity occur at higher coupling via period doubling sequences. The associated
      spatial patterns of photon and carrier lattice distribution resemble photonic
      convection cells. Limit cycles of different periods, emanating mathematically
      from different original fixed points, coexist at high strengths, each one
      accessible from different initial conditions. The multiplicity of possible limit
      cycles in systems with many degrees of freedom (number of lattice sites) combined
      with changes in their accessibility from initial conditions offers new insights
      to chaotic transitions, compared to low dimensionality paradigms.

PMID- 15568926
TI  - On the origin of reproducible sequential activity in neural circuits.
AB  - Robustness and reproducibility of sequential spatio-temporal responses is an
      essential feature of many neural circuits in sensory and motor systems of
      animals. The most common mathematical images of dynamical regimes in neural
      systems are fixed points, limit cycles, chaotic attractors, and continuous
      attractors (attractive manifolds of neutrally stable fixed points). These are not
      suitable for the description of reproducible transient sequential neural
      dynamics. In this paper we present the concept of a stable heteroclinic sequence
      (SHS), which is not an attractor. SHS opens the way for understanding and
      modeling of transient sequential activity in neural circuits. We show that this
      new mathematical object can be used to describe robust and reproducible
      sequential neural dynamics. Using the framework of a generalized high-dimensional
      Lotka-Volterra model, that describes the dynamics of firing rates in an
      inhibitory network, we present analytical results on the existence of the SHS in
      the phase space of the network. With the help of numerical simulations we confirm
      its robustness in presence of noise in spite of the transient nature of the
      corresponding trajectories. Finally, by referring to several recent
      neurobiological experiments, we discuss possible applications of this new concept
      to several problems in neuroscience.

PMID- 15568927
TI  - Nonintegrable Schrodinger discrete breathers.
AB  - In an extensive numerical investigation of nonintegrable translational motion of
      discrete breathers in nonlinear Schrodinger lattices, we have used a regularized
      Newton algorithm to continue these solutions from the limit of the integrable
      Ablowitz-Ladik lattice. These solutions are shown to be a superposition of a
      localized moving core and an excited extended state (background) to which the
      localized moving pulse is spatially asymptotic. The background is a linear
      combination of small amplitude nonlinear resonant plane waves and it plays an
      essential role in the energy balance governing the translational motion of the
      localized core. Perturbative collective variable theory predictions are
      critically analyzed in the light of the numerical results.

PMID- 15568928
TI  - Emergence of chaotic attractor and anti-synchronization for two coupled
      monostable neurons.
AB  - The dynamics of two coupled piece-wise linear one-dimensional monostable maps is
      investigated. The single map is associated with Poincare section of the FitzHugh
      Nagumo neuron model. It is found that a diffusive coupling leads to the
      appearance of chaotic attractor. The attractor exists in an invariant region of
      phase space bounded by the manifolds of the saddle fixed point and the saddle
      periodic point. The oscillations from the chaotic attractor have a spike-burst
      shape with anti-phase synchronized spiking.

PMID- 15568931
TI  - Elastic scattering spectroscopy for intraoperative determination of sentinel
      lymph node status in the breast.
AB  - The ability to provide the best treatment for breast cancer depends on
      establishing whether or not the cancer has spread to the lymph nodes under the
      arm. Conventional assessment requires tissue removal, preparation, and expert
      microscopic interpretation. In this study, elastic scattering spectroscopy (ESS)
      is used to interrogate excised nodes with pulsed broadband illumination and
      collection of the backscattered light. Multiple spectra are taken from 139
      excised nodes (53 containing cancer) in 68 patients, and spectral analysis is
      performed using a combination of principal component analysis and linear
      discriminant analysis to correlate the spectra with conventional histology. The
      data are divided into training and test sets. In test sets containing spectra
      from only normal nodes and nodes with complete replacement by cancer, ESS detects
      the spectra from cancerous nodes with 84% sensitivity and 91% specificity (per
      spectrum analysis). In test sets that included normal nodes and nodes with
      partial as well as complete replacement by cancer, ESS detects the nodes with
      cancer with an average sensitivity of 75% and specificity of 89% (per-node
      analysis). These results are comparable to those from conventional touch imprint
      cytology and frozen section histology, but do not require an expert pathologist
      for interpretation. With automation of the technique, results could be made
      available almost instantaneously. ESS is a promising technique for the rapid,
      accurate, and straightforward detection of metastases in excised sentinel lymph
      nodes.

PMID- 15568932
TI  - Intraoperatively assessed optical properties of malignant and healthy breast
      tissue used to determine the optimum wavelength of contrast for optical
      mammography.
AB  - We use spatially resolved diffuse remittance spectroscopy (DRS) for the
      measurement of absorption (mu(a)) and reduced scattering (mu(s)') coefficients of
      normal and malignant breast tissue in vivo during surgery. Prior to these
      measurements, the linearity of the measurement technique was evaluated on liquid
      optical phantoms. In addition, the reproducibility of in-vivo tissue measurements
      was determined on a healthy volunteer. We present results of the in-vivo
      measurement of optical properties in the wavelength range from 600 to 1100 nm
      performed during radical mastectomy. A total of 24 patients were included in the
      study. Both the absorption and reduced scattering properties show large
      variations. Significant differences in optical properties between normal
      (glandular plus lipid rich tissue) and tumor tissues are present in 74% of all
      patients. However, in some cases the tumor showed lower values than normal
      tissue, and in other cases this was the other way around. Thus, a general trend
      in optical properties is not observed. However, the average absorption contrast
      of all patients as a function of wavelength reveals an optimal contrast peak at
      650 nm. We believe that this relates to a difference in vascular saturation
      between tumor and adjacent normal tissue.

PMID- 15568933
TI  - Bulk optical properties and tissue components in the female breast from
      multiwavelength time-resolved optical mammography.
AB  - We present the results of a clinical study about optical properties and bulk
      composition of the female breast. The clinical study involved more than 150
      subjects that underwent optical mammography. A multiwavelength time-resolved
      mammograph designed to collect time-resolved transmittance images of the breast
      at different wavelengths in the range 637 to 980 nm is used to this purpose. From
      the absorption spectrum of the breast, the concentrations of the main tissue
      constituents, i.e., oxygenated and deoxygenated hemoglobin, lipid, and water, are
      obtained for a subset of 113 breasts. The lipid content of breast is estimated
      for the first time on such a large number of subjects. The total hemoglobin
      concentration, blood oxygen saturation, lipid, and water content of breast is
      correlated to demographic information collected during the trial. As expected,
      breast optical properties and components undergo huge variations among different
      subjects. Different constituents, however, show interesting correlation with
      clinical parameters such as age, breast size, body mass index, and mammographic
      parenchymal pattern. These results suggest that optical measurements on breasts
      can be exploited to obtain relevant information on breast tissue composition.

PMID- 15568934
TI  - Spectroscopic time-resolved diffuse reflectance and transmittance measurements of
      the female breast at different interfiber distances.
AB  - The first, to our knowledge, in-vivo broadband spectroscopic characterization of
      breast tissue using different interfiber distances as well as transmittance
      measurements is presented. Absorption and scattering properties are measured on
      six healthy subjects, using time-resolved diffuse spectroscopy and an inverse
      model based on the diffusion equation. Wavelength-tunable picosecond-pulse lasers
      and time-correlated single-photon counting detection are employed, enabling fully
      spectroscopic measurements in the range 610 to 1040 nm. Characterization of the
      absorption and reduced scattering coefficients of breast tissue is made with the
      aim of investigating individual variations, as well as variations due to
      different measurement geometries. Diffuse reflectance measurements at different
      interfiber distances (2, 3, and 4 cm) are performed, as well as measurements in
      transmittance mode, meaning that different sampling volumes are involved. The
      results show a large variation in the absorption and scattering properties
      depending on the subject, correlating mainly with the water versus lipid content
      of the breast. Intrasubject variations, due to different interfiber distances or
      transmittance modes, correlate with the known structures of the breast, but these
      variations are small compared to the subject-to-subject variation. The
      intrasubject variations are larger for the scattering data than the absorption
      data; this is consistent with different spatial localization of the measurements
      of these parameters, which is explained by the photon migration theory.

PMID- 15568935
TI  - Near-infrared imaging of the human breast: complementing hemoglobin concentration
      maps with oxygenation images.
AB  - We have previously reported a comparison between edge-corrected near-infrared
      optical mammograms and those that have undergone a further image-processing step
      based on a spatial second derivative. In this work, we go a step further by
      combining the second-derivative images from four wavelengths (690, 750, 788, and
      856 nm) to obtain oxygenation-index images. While the spatial second derivative
      improves contrast and allows for visibility of fine structures in the images,
      thereby improving the sensitivity to tumor detection, additional information is
      needed to avoid false-positive results. The oxygenation-index images are
      introduced to address this issue. Oxygenation information may help discriminate
      benign from malignant breast lesions, thereby effectively complementing single
      wavelength optical mammograms that display optically dense regions within the
      breast with high sensitivity.

PMID- 15568936
TI  - Improved quantification of small objects in near-infrared diffuse optical
      tomography.
AB  - Diffuse optical tomography allows quantification of hemoglobin, oxygen
      saturation, and water in tissue, and the fidelity in this quantification is
      dependent on the accuracy of optical properties determined during image
      reconstruction. In this study, a three-step algorithm is proposed and validated
      that uses the standard Newton minimization with Levenberg-Marquardt
      regularization as the first step. The second step is a modification to the
      existing algorithm using a two-parameter regularization to allow lower damping in
      a region of interest as compared to background. This second stage allows the
      recovery of the actual size of an inclusion. A region-based reconstruction is the
      final third step, which uses the estimated size and position information from
      step 2 to yield quantitatively accurate average values for the optical
      parameters. The algorithm is tested on simulated and experimental data and is
      found to be insensitive to object contrast and position. The percentage error
      between the true and the average recovered value for the absorption coefficient
      in test images is reduced from 47 to 27% for a 10-mm inclusion, from 38 to 13%
      for a 15-mm anomaly, and from 28 to 5.5% for a 20-mm heterogeneity. Simulated
      data with absorbing and scattering heterogeneities of 15 mm diam located in
      different positions show recovery with less than 15% error in absorption and 6%
      error in reduced scattering coefficients. The algorithm is successfully applied
      to clinical data from a subject with a breast abnormality to yield quantitatively
      increased absorption coefficients, which enhances the contrast to 3.8 compared to
      1.23 previously.

PMID- 15568937
TI  - Photoacoustic mammography laboratory prototype: imaging of breast tissue
      phantoms.
AB  - We present a laboratory version of a photoacoustic mammoscope, based on a
      parallel plate geometry. The instrument is built around a flat high-density
      ultrasound detector matrix. The light source is a Q-switched Nd:YAG laser with a
      pulse duration of 5 ns. To test the instrument, a novel photoacoustic phantom is
      developed using poly(vinyl alcohol) gel, prepared by a simple procedure that
      imparts optical scattering suggestive of breast tissue to it without the
      requirement for extraneous scattering particles. Tumor simulating poly(vinyl
      alcohol) gel spheres appropriately dyed at the time of preparation are
      characterized for optical absorption coefficients. These are then embedded in the
      phantom to serve as tumors with absorption contrasts ranging from 2 to 7, with
      respect to the background. Photoacoustic studies in transmission mode are
      performed, by acquiring the laser-induced ultrasound signals from regions of
      interest in the phantom. Image reconstruction is based on a delay-and-sum
      beamforming algorithm. The results of these studies provide an insight into the
      capabilities of the prototype. Various recommendations that will guide the
      evolving of our laboratory prototype into a clinical version are also discussed.

PMID- 15568938
TI  - Measurement of bacterial concentration fractions in polymicrobial mixtures by
      Raman microspectroscopy.
AB  - Relative concentrations of Streptococcus mutans and Streptococcus sanguis are
      important parameters in the study of dental caries, but current methods of
      measuring these concentrations are time consuming and prone to inaccuracies. We
      investigate the use of Raman spectroscopy for measuring relative concentrations
      of these two bacterial species in solid mixtures. To our knowledge, this is the
      first time Raman spectroscopy has been used to analyze bacterial mixtures rather
      than to identify the species of a pure colony. Mixtures of the two streptococcal
      species in various ratios are measured for 200 s using a home-built Raman
      microscope. Spectral correlations with bacterial content were identified via
      partial least-squares analysis. The relative concentrations of S. mutans in
      subsequent samples are predicted with a root mean squared error below 5%. In
      clinical plaque samples, this sort of accuracy would enable discrimination
      between normal and dangerously elevated levels of S. mutans. Samples with and
      without salivary proteins are predicted with equal accuracy. This result shows
      the potential of Raman spectroscopy for analyzing mixed populations of bacteria,
      such as those that occur in oral plaques.

PMID- 15568939
TI  - Raman microspectroscopic mapping studies of human bronchial tissue.
AB  - Characterization of the biochemical composition of normal bronchial tissue is a
      prerequisite for understanding the biochemical changes that accompany
      histological changes during lung cancer development. In this study, 12 Raman
      microspectroscopic mapping experiments are performed on frozen sections of normal
      bronchial tissue. Pseudocolor Raman images are constructed using principal
      component analysis and K-means cluster analysis. Subsequent comparison of Raman
      images with histologic evaluation of stained sections enables the identification
      of the morphologic origin (e.g., bronchial mucus, epithelium, fibrocollagenous
      stroma, smooth muscle, glandular tissue, and cartilage) of the spectral features.
      Raman spectra collected from the basal side of epithelium consistently show
      higher DNA contributions and lower lipid contributions when compared with
      superficial epithelium spectra. Spectra of bronchial mucus reveal a strong signal
      contribution of lipids, predominantly triolein. These spectra are almost
      identical to the spectra obtained from submucosal glands, which suggests that the
      bronchial mucus is mainly composed of gland secretions. Different parts of
      fibrocollagenous tissue are distinguished by differences in spectral
      contributions from collagen and actin/myosin. Cartilage is identified by spectral
      contributions of glycosaminoglycans and collagen. As demonstrated here, in situ
      analysis of the molecular composition of histologic structures by Raman
      microspectroscopic mapping creates powerful opportunities for increasing our
      fundamental understanding of tissue organization and function. Moreover, it
      provides a firm basis for further in vitro and in vivo investigations of the
      biochemical changes that accompany pathologic transformation of tissue.

PMID- 15568940
TI  - Raman spectroscopy of in vivo cutaneous melanin.
AB  - We successfully acquire the in vivo Raman spectrum of melanin from human skin
      using a rapid near-infrared (NIR) Raman spectrometer. The Raman signals of in
      vivo cutaneous melanin are similar to those observed from natural and synthetic
      eumelanins. The melanin Raman spectrum is dominated by two intense and broad
      peaks at about 1580 and 1380 cm(-1), which can be interpreted as originating from
      the in-plane stretching of the aromatic rings and the linear stretching of the C
      C bonds within the rings, along with some contributions from the C-H vibrations
      in the methyl and methylene groups. Variations in the peak frequencies and
      bandwidths of these two Raman signals due to differing biological environments
      have been observed in melanin from different sources. The ability to acquire
      these unique in vivo melanin signals suggests that Raman spectroscopy may be a
      useful clinical method for noninvasive in situ analysis and diagnosis of the
      skin.

PMID- 15568941
TI  - Determination of the modulation transfer function for a time-gated fluorescence
      imaging system.
AB  - The use of fluorescence for cancer detection is currently under investigation.
      Presently, steady-state fluorescence detection methods are in use, but have
      limitations due to poor contrast between the fluorescence of the tumor and
      background autofluorescence. Improved contrast can be obtained with time-resolved
      techniques because of the differing lifetimes between autofluorescence and
      exogenous photosensitizers that selectively accumulate within tumor tissue. An
      imaging system is constructed using a fast-gated (200-ps) charge-coupled device
      (CCD) camera and a pulsed 635-nm laser diode. To characterize the ability of the
      system to transfer object contrast to an image, the modulation transfer function
      (MTF) of the system is acquired by employing an extended knife-edge technique. A
      knife-edge target is assembled by drilling a rectangular well into a block of
      polymethyl methacrylate (PMMA). The imaging system records images of the
      photosensitizer, chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), within
      the well. AlPcTS was chosen to test the system because of its strong absorption
      of 635-nm, high fluorescence yield, and relatively long fluorescence lifetime
      (approximately 7.5 ns). The results show that the system is capable of resolving
      10(-4) M AlPcTS fluorescence as small as 1 mm. The findings of this study
      contribute to the development of a time-gated imaging system using fluorescence
      lifetimes.

PMID- 15568942
TI  - In vivo measurement of time-resolved autofluorescence at the human fundus.
AB  - An experimental setup for measurement of time-resolved autofluorescence of the
      human eye fundus is demonstrated. The method combines laser scanning technique
      and time-correlated single photon counting. The light source is a laser diode,
      delivering pulses of about 100 ps duration at a repetition rate of 40 MHz. The
      excitation wavelength is 446 nm and the cutoff wavelength of fluorescence
      detection is at 475 nm. The autofluorescence can be determined with a spatial
      resolution of 80 x 80 microm2 and 25 ps time resolution. The fluorescence decay
      is optimally approximated by a biexponential model. The dominating lifetime tau1
      is shortest in the macula (320 to 380 ps) and reaches 1500 ps in the optic disk.
      The lifetime tau2 varies between 2 ns and 5 ns, but the spatial distribution is
      more homogeneous. Respiration of 100% oxygen for 6 min leads to changes in the
      fluorescence lifetime pointing to detection of coenzymes. Diagrams of lifetime
      tau2 versus tau1 are well suited for comparison of substances. Such lifetime
      clusters of a 20 deg macular field of a young healthy subject and of a patient
      suffering from dry age-related macular degeneration overlap only partially with
      tau2-tau1 clusters of lipofuscin.

PMID- 15568943
TI  - Detection of dual-gene expression in arteries using an optical imaging method.
AB  - We evaluate the in vivo use of an optical imaging method to detect the vascular
      expression of green fluorescent protein (GFP) or red fluorescent protein (RFP),
      and to detect the simultaneous expression of GFP and RFP after transduction into
      arteries by a dual-promoter lentiviral vector driving their concurrent
      expression. This method involves using a charge-coupled device camera to detect
      fluorescence, a fiber optic probe to transmit light, and optical filters to
      distinguish each marker. In animal models, these vectors are locally delivered to
      target arteries, whereas the gene for a nonfluorescent cell-surface protein is
      transduced into contralateral arteries as the sham control. The images show
      distinct areas of bright fluorescence from GFP and RFP along the target arteries
      on excitation; no exogenous fluorescence is observed in the controls. Measured
      signal intensities from arteries transduced with the single- and dual-promoter
      vectors exceed the autofluorescence signal from the controls. Transgene
      expression of GFP and RFP in vivo is confirmed with confocal microscopy. We
      demonstrate the use of an optical imaging method to concurrently detect two
      distinct fluorescent proteins, potentially permitting the expression of multiple
      transgenes and their localization in the vasculature to be monitored.

PMID- 15568944
TI  - Fast fluorescence lifetime imaging of calcium in living cells.
AB  - A fast fluorescence lifetime imaging (FLIM) system is developed that can acquire
      images at a rate of hundreds of frames per second. The FLIM system is based on a
      wide-field microscope equipped with a time-gated intensified CCD detector and a
      pulsed laser. The time-gated detector acquires the signals from two time gates
      simultaneously and is therefore insensitive to movements of the specimen and
      photo-bleaching. The system is well suited for quantitative biological FLIM
      experiments and its performance is evaluated in calcium imaging experiments on
      beating neonatal rat myocytes. Several calcium sensitive dyes are characterized
      and tested for their suitability for fast FLIM experiments: Oregon Green Bapta-1
      (OGB1), Oregon Green Bapta-2 (OGB2), and Oregon Green Bapta-5N (OGB5N). Overall
      the sensitivity range of these dyes is shifted to low calcium concentrations when
      used as lifetime dyes. OGB1 and OGB2 behave very similarly and can be used for
      FLIM-based calcium imaging in the range 1 to approximately 500 nM and OGB5N can
      be used up to 3 microM. The fast FLIM experiments on the myocytes could be
      carried out at a 100-Hz frame rate. During the beating of the myocytes a lifetime
      change of about 20% is observed. From the lifetime images a rest calcium level of
      about 65 nM is found.

PMID- 15568945
TI  - Focused ion beam for microscopy and in situ sample preparation: application on a
      crustacean digestive system.
AB  - We prove that the focused ion beam (FIB) machine can be used as a microscope and
      as an in situ cutting device for tissue and cells. For the first time we obtain
      high-resolution ion images, complemented by electron imaging of different animal
      tissues both from uncoated and coated samples. In our study, we select the
      digestive system of Porcellio scaber (isopoda, crustacea) as a test system for
      FIB microscopy and in situ sample preparation. After the milling operation, some
      of the ultrastructural elements of hepatopancreatic cells can clearly be
      recognized. Also, FIB operation reveals significant differences in structural
      integrity between the apical and basal parts of hepatopancreatic cells, which
      have not been observed before by classical microscopy techniques. FIB microscopy
      and in situ sample preparation have advantages over classical microscopy
      techniques because of: 1. in situ site-specific 2-D sectioning and imaging of
      subsurface microstructures; 2. no need to embed the sample prior to sectioning;
      and 3. a wide range of magnifications while imaging the same sample.

PMID- 15568946
TI  - Optimizing low-light microscopy with back-illuminated electron multiplying charge
      coupled device: enhanced sensitivity, speed, and resolution.
AB  - The back-illuminated electron multiplying charge-coupled device (EMCCD) camera is
      having a profound influence on the field of low-light dynamic cellular
      microscopy, combining highest possible photon collection efficiency with the
      ability to virtually eliminate the readout noise detection limit. We report here
      the use of this camera, in 512 x 512 frame-transfer chip format at 10-MHz pixel
      readout speed, in optimizing a demanding ultra-low-light intracellular calcium
      flux microscopy setup. The arrangement employed includes a spinning confocal
      Nipkow disk, which, while facilitating the need to both generate images at very
      rapid frame rates and minimize background photons, yields very weak signals. The
      challenge for the camera lies not just in detecting as many of these scarce
      photons as possible, but also in operating at a frame rate that meets the
      temporal resolution requirements of many low-light microscopy approaches, a
      particular demand of smooth muscle calcium flux microscopy. Results presented
      illustrate both the significant sensitivity improvement offered by this
      technology over the previous standard in ultra-low-light CCD detection, the
      GenIII+intensified charge-coupled device (ICCD), and also portray the advanced
      temporal and spatial resolution capabilities of the EMCCD.

PMID- 15568947
TI  - Mitigating thermal mechanical damage potential during two-photon dermal imaging.
AB  - Two-photon excitation fluorescence microscopy allows in vivo high-resolution
      imaging of human skin structure and biochemistry with a penetration depth over
      100 microm. The major damage mechanism during two-photon skin imaging is
      associated with the formation of cavitation at the epidermal-dermal junction,
      which results in thermal mechanical damage of the tissue. In this report, we
      verify that this damage mechanism is of thermal origin and is associated with one
      photon absorption of infrared excitation light by melanin granules present in the
      epidermal-dermal junction. The thermal mechanical damage threshold for selected
      Caucasian skin specimens from a skin bank as a function of laser pulse energy and
      repetition rate has been determined. The experimentally established thermal
      mechanical damage threshold is consistent with a simple heat diffusion model for
      skin under femtosecond pulse laser illumination. Minimizing thermal mechanical
      damage is vital for the potential use of two-photon imaging in noninvasive
      optical biopsy of human skin in vivo. We describe a technique to mitigate
      specimen thermal mechanical damage based on the use of a laser pulse picker that
      reduces the laser repetition rate by selecting a fraction of pulses from a laser
      pulse train. Since the laser pulse picker decreases laser average power while
      maintaining laser pulse peak power, thermal mechanical damage can be minimized
      while two-photon fluorescence excitation efficiency is maximized.

PMID- 15568948
TI  - Detection and diagnosis of oral neoplasia with an optical coherence microscope.
AB  - The use of high resolution, in vivo optical imaging may offer a clinically useful
      adjunct to standard histopathologic techniques. A pilot study was performed to
      investigate the diagnostic capabilities of optical coherence microscopy (OCM) to
      discriminate between normal and abnormal oral tissue. Our objective is to
      determine whether OCM, a technique combining the subcellular resolution of
      confocal microscopy with the coherence gating and heterodyne detection of optical
      coherence tomography, has the same ability as confocal microscopy to detect
      morphological changes present in precancers of the epithelium while providing
      superior penetration depths. We report our results using OCM to characterize the
      features of normal and neoplastic oral mucosa excised from 13 subjects.
      Specifically, we use optical coherence and confocal microscopic images obtained
      from human oral biopsy specimens at various depths from the mucosal surface to
      examine the optical properties that distinguish normal and neoplastic oral
      mucosa. An analysis of penetration depths achieved by the OCM and its associated
      confocal arm found that the OCM consistently imaged more deeply. Extraction of
      scattering coefficients from reflected nuclear intensity is successful in
      nonhyperkeratotic layers and shows differentiation between scattering properties
      of normal and dysplastic epithelium and invasive cancer.

PMID- 15568949
TI  - Adaptive spectral apodization for sidelobe reduction in optical coherence
      tomography images.
AB  - Often in imaging systems, the bandpass of the system is not uniform. In temporal
      coherence imaging methods such as optical coherence tomography, one would like to
      achieve the most spatially confined impulse response possible with a given source
      spectrum, minimizing sidelobes that blur adjacent features together. Typically
      the spectrum of the source is controlled in order to remove sidelobes from the
      measured interferogram. However, the measured interferogram is not necessarily
      the best estimate of the scattering density of the object. In this work, a
      sidelobe supression method is proposed and demonstrated to achieve low sidelobes
      even with highly nonuniform, non-Gaussian spectra.

PMID- 15568950
TI  - Retinal response of Macaca mulatta to picosecond laser pulses of varying energy
      and spot size.
AB  - We investigate the relationship between the laser beam at the retina (spot size)
      and the extent of retinal injury from single ultrashort laser pulses. From
      previous studies it is believed that the retinal effect of single 3-ps laser
      pulses should vary in extent and location, depending on the occurrence of laser
      induced breakdown (LIB) at the site of laser delivery. Single 3-ps pulses of 580
      nm laser energy are delivered over a range of spot sizes to the retina of Macaca
      mulatta. The retinal response is captured sequentially with optical coherence
      tomography (OCT). The in vivo OCT images and the extent of pathology on final
      microscopic sections of the laser site are compared. With delivery of a laser
      pulse with peak irradiance greater than that required for LIB, OCT and light
      micrographs demonstrate inner retinal injury with many intraretinal and/or
      vitreous hemorrhages. In contrast, broad outer retinal injury with minimal to no
      choriocapillaris effect is seen after delivery of laser pulses to a larger
      retinal area (60 to 300 microm diam) when peak irradiance is less than that
      required for LIB. The broader lesions extend into the inner retina when higher
      energy delivery produces intraretinal injury. Microscopic examination of stained
      fixed tissues provide better resolution of retinal morphology than OCT. OCT
      provides less resolution but could be guided over an in vivo, visible retinal
      lesion for repeated sampling over time during the evolution of the lesion
      formation. For 3-ps visible wavelength laser pulses, varying the spot size and
      laser energy directly affects the extent of retinal injury. This again is
      believed to be partly due to the onset of LIB, as seen in previous studies. Spot
      size dependence should be considered when comparing studies of retinal effects or
      when pursuing a specific retinal effect from ultrashort laser pulses.

PMID- 15568951
TI  - Imaging artificial caries under composite sealants and restorations.
AB  - Polarization-sensitive optical coherence tomography (PS-OCT) is used to monitor
      the progression of simulated caries lesions on occlusal surfaces and image the
      lesions underneath composite sealants. The polarization-sensitive system,
      recording images in both the parallel and perpendicular axes, is useful for
      enhancing the image contrast of the artificial caries and minimizing the
      interference of the strong reflections at surface interfaces. Using the
      perpendicular-axis signal, the mean reflectivity increase from day 0 to day 14 is
      5.1 dB (p<0.01, repeated-measures analysis of variation, Tukey-Kramer). For
      imaging lesions underneath the sealants, the mean reflectivity of the enamel
      underneath 250, 500, 750, and 1000 microm of composite is calculated for
      demineralized and control samples. The artificial lesions can be detected under
      750 microm of visibly opaque sealant, with a 5.0-dB difference from the control
      samples (t-test, p<0.001). Tooth colored sealants allow deeper imaging depth. The
      artificial lesions could be detected under 1000 microm of sealant, with a 6.6-dB
      difference from the control samples (t-test, p<0.001). This study demonstrates
      that PS-OCT can be used to track lesion progression on occlusal surfaces
      nondestructively with or without sealants.

PMID- 15568952
TI  - Design, testing, and clinical studies of a handheld polarized light camera.
AB  - Polarized light imaging has been used to detect the borders of skin cancer and
      facilitate assessment of cancer boundaries. A design for an inexpensive handheld
      polarized camera is presented and clinical images acquired with this prototype
      are shown. The camera is built with two universal serial bus (USB) color video
      cameras, a polarizing beamsplitter cube, and a 4x objective lens. Illumination is
      provided by three white LEDs and a sheet polarizer. Horizontal and vertical
      linearly polarized reflected images are processed at 7 frames/s and a resulting
      polarized image is displayed on screen. We compare the performances of cheap USB
      camera and a 16-bit electronically cooled camera. Dark noise and image
      repeatability are compared. In both cases, the 16-bit camera outperforms the USB
      cameras. Despite these limitations, the results obtained with this USB prototype
      are very satisfactory. Examples of polarized images of lesions taken prior to
      surgery are presented.

PMID- 15568953
TI  - Low-frequency surface wave propagation and the viscoelastic behavior of porcine
      skin.
AB  - A physical model describing the propagation of low-frequency surface waves in
      relation to the viscoelastic behavior of porcine skin is presented, along with a
      series of empirical studies testing the performance of the model. The model
      assumes that the skin behaves as a semi-infinite, locally isotropic, viscoelastic
      half-space. While the assumption of a semi-infinite body is violated, this
      violation does not appear to have a significant impact on the performance of the
      model based on the empirical studies. 1-Hz surface waves in the skin propagate
      primarily as Rayleigh waves with a wavelength and velocity of approximately 3 m
      and 3.0 m/s, respectively. The amplitude of the acoustic wave, as measured by
      tracking the acoustic stress wave-induced shift in a backscattered laser speckle
      pattern, decreases exponentially with lateral distance from the acoustic source.
      Using this model of surface wave propagation, the mechanical loss factor or tan
      delta of the skin is measured to be on the order of 0.14+/-0.07. The results
      presented are consistent with earlier works on the propagation of low-frequency
      acoustic waves in biological tissues, and should serve as a theoretical and
      empirical basis for using the wave characteristics of propagating surface waves
      in combination with the mechanical behavior of the tissue for biomechanical
      studies and for potential diagnostic applications.

PMID- 15568954
TI  - Comparison between ultraviolet-visible and near-infrared elastic scattering
      spectroscopy of chemically induced melanomas in an animal model.
AB  - The work reported compares elastic scattering spectroscopy (ESS) for diagnosis of
      pigmented skin lesions in two spectral regions: UV-visible and near infrared
      (NIR). Given the known strong absorption by melanin in the near-UV to mid-visible
      range of the spectrum, such a comparison can help determine the optimum
      wavelength range of ESS for diagnosis of pigmented skin lesions. For this
      purpose, four South American opossums are treated with dimethylbenz(a)anthracene
      on multiple dorsal sites to induce both malignant melanomas and benign pigmented
      lesions. Skin lesions are examined in vivo with ESS using both UV-visible and
      NIR, with wavelength ranges of 330 to 900 nm and 900 to 1700 nm, respectively.
      Both portable systems use the same fiber optic probe geometry. ESS measurements
      are made on the lesions, and spectral differences are grouped by diagnosis from
      standard histopathological procedure. Both ESS datasets show strong spectral
      trends with the histopathological assignments, and the data suggest a model for
      the underlying basis of the spectral distinction between benign and malignant
      pigmented nevi.

PMID- 15568955
TI  - Photoacoustic imaging of blood vessels with a double-ring sensor featuring a
      narrow angular aperture.
AB  - A photoacoustic double-ring sensor, featuring a narrow angular aperture, is
      developed for laser-induced photoacoustic imaging of blood vessels. An integrated
      optical fiber enables reflection-mode detection of ultrasonic waves. By using the
      cross-correlation between the signals detected by the two rings, the angular
      aperture of the sensor is reduced by a factor of 1.9, from 1.5 to 0.8 deg.
      Consequently, photoacoustic images could be obtained in a manner analogous to the
      ultrasound B-scan mode. Next, the cross section of artificial blood vessels is
      visualized by reconstruction of the absorbed energy distribution. Finally, in
      vivo imaging and the subsequent reconstruction of the absorbed energy
      distribution is demonstrated for superficial blood vessels in the human wrist.

PMID- 15568956
TI  - Determination of optical properties in semi-infinite turbid media using imaging
      measurements of frequency-domain photon migration obtained with an intensified
      charge-coupled device.
AB  - Frequency-domain photon migration measurements across the surface of a tissue
      mimicking, semi-infinite phantom are acquired via an intensified charge-coupled
      device (ICCD) detection system and used in conjunction with the diffusion
      approximation to determine the optical properties. The absorption and reduced
      scattering coefficients are determined least accurately when relative
      measurements of average light intensity I(rel)dc are employed either alone or in
      a combination with relative modulation amplitude data I(rel)ac and/or relative
      phase shift data theta(rel). The absorption and reduced scattering coefficients
      are found accurate to within 15 and 11%, respectively, of the values obtained
      from standard single-pixel measurements when theta(rel) measurements are employed
      alone or in combination with I(rel)ac data.

PMID- 15568957
TI  - Detection of differences in oligonucleotide-influenced aggregation of colloidal
      gold nanoparticles using absorption spectroscopy.
AB  - A rapid, simple, and reproducible assay is described that can be used to detect
      differences in the ability of oligonucleotides to influence the aggregation of
      colloidal gold nanoparticles. The aggregation reaction of the gold colloid was
      monitored through UV-visible absorption spectroscopy. Single isolated colloidal
      gold particles have a surface plasmon resonance manifested as a single absorbance
      peak at approximately 520 nm, and aggregated gold complexes develop new red
      shifted peaks/shoulders depending on the nature and extent of the aggregated
      complex. A simple ratiometric study of the area under the single and aggregated
      plasmon resonance peaks thus gives information about the extent of the
      aggregation. It is postulated that differences in dynamic flexibility of the
      oligonucleotides affect their influence on the aggregation state of the gold
      nanoparticles. The results of this study provide new clues toward unraveling the
      causes behind the preferential affinity of the Hermes transposable element for
      certain insertion sites compared to other sequences that also contain
      recognizable target sites. The technique is robust and thus can potentially be
      used to study similar questions for numerous transposable elements and target
      sequences.

PMID- 15568958
TI  - Influence of nonhomogeneous distribution of topically applied UV filters on sun
      protection factors.
AB  - The aim of the present study is the development of a method to determine
      quantitatively in vivo the influence of homogeneity of the distribution of
      sunscreen containing UV filters on the sun protection factor (SPF). The SPF of a
      sunscreen applied either topically or inside an optical cell (pure or in a
      solvent) fixed above the skin is determined in vivo. In both cases, in vivo
      measurements using the erythema formation are carried out. Identical optical
      parameters of the skin are realized in both experiments. In addition, both in
      vitro (using tape stripping) and in vivo microscopic measurements are performed
      to analyze the homogeneity of distribution of the topically applied substances.
      An SPF of 8 is measured in the experiment applying the UV filters topically,
      whereas this value increases by a factor of 10 if the same amount of filter
      substances is distributed homogeneously in solution inside the optical cell. Tape
      strips removed from skin treated with the sunscreen reflect the inhomogeneous
      distribution of the topically applied substances on the skin. The direct
      correlation of homogeneity of distribution with the SPF opens up the possibility
      to increase the SPF by optimizing the formulation.

PMID- 15568959
TI  - Pediatric Vision Screener 1: instrument design and operation.
AB  - We develop the Pediatric Vision Screener (PVS) to automatically detect ocular
      misalignment (strabismus) and defocus in human subjects. The PVS utilizes
      binocular retinal birefringence scanning to determine when both eyes are aligned,
      with a theoretical accuracy of <1 deg. The device employs an autoconjugate,
      bull's-eye detector-based system to detect focus. The focus and alignment
      pathways are separated by both wavelength and data acquisition timing. Binocular
      focus and alignment are detected in rapid alternating sequence, measuring both
      parameters in both eyes in <0.5 sec. In this work, the theory and design of the
      PVS are described in detail. With objective, automated measurement of both
      alignment and focus, the PVS represents a new approach to screening children for
      treatable eye disease such as amblyopia.

PMID- 15568960
TI  - Pediatric Vision Screener 2: pilot study in adults.
AB  - Amblyopia is a form of visual impairment caused by ocular misalignment
      (strabismus) or defocus in an otherwise healthy eye. If detected early, the
      condition can be fully treated, yet over half of all children with amblyopia
      under age 5 escape detection. We developed a Pediatric Vision Screener (PVS) to
      detect amblyopia risk factors. This instrument produces a binocularity score to
      indicate alignment and a focus score to indicate focus. The purpose of this study
      is to assess the performance of the PVS by testing adults who were fully
      cooperative for testing. The study group includes 40 subjects (20 controls, 20
      patients) aged 22 to 79 years. 12 patients had constant strabismus (8 to
      50Delta), and eight had variable strabismus (12 to 55Delta). All controls had
      binocularity scores >50%. Binocularity was <50% in 11/12 patients. The patient
      with binocularity >50% had a well-controlled intermittent exotropia and was not
      at risk for amblyopia. Focus scores were highly sensitive for good focus but not
      specific. The PVS shows high sensitivity and specificity for detection of
      strabismus in adults. Future studies will determine whether this performance can
      be achieved in preschool children, who are at greatest risk for vision loss.

PMID- 15568961
TI  - Long-term outcome for people with severe intellectual disabilities: impact of
      social impairment.
AB  - Results from a 25-year follow-up study of the Camberwell Cohort (L. Wing & Gould,
      1978, 1979) were presented. Ninety-one people, ranging in age from 27 to 41
      years, were traced, and an outcome measure was developed incorporating
      independent functioning, residential placement, employment, and quality of life.
      Outcome was rated as either poor (53%) or fair (43%), with only 3% having a good
      outcome. Using logistic regression methods, we found that the best predictor of
      outcome was social impairment, with those who were socially impaired,
      particularly those in the aloof category, having a poorer outcome. Higher IQ at
      Time 1 and lower challenging behavior were also predictive of better outcome. An
      in-depth look at social impairment revealed that social impairment remained
      stable over time.

PMID- 15568962
TI  - Generative learning during visual search for scene changes: enhancing free recall
      of individuals with and without mental retardation.
AB  - Memory for scene changes that were identified immediately (passive encoding) or
      following systematic and effortful search (generative encoding) was compared
      across groups differing in age and intelligence. In the context of flicker
      methodology, generative search for the changing object involved selection and
      rejection of multiple potential solutions prior to identification of the correct
      object. Such "incorrect guesses" were designed to serve as effective retrieval
      cues during free recall. All groups recalled more changes from the generative
      encoding than from the passive-encoding condition. Results demonstrate the
      efficacy of generative encoding contexts for enhancing free recall in individuals
      with and without mental retardation and the promise of such methodologies for
      computerized learning environments.

PMID- 15568963
TI  - Misdiagnosis of thyroid disorders in down syndrome: time to re-examine the myth?
AB  - There is a reported association between thyroid disorders and Down syndrome, but
      is this association based on valid and reliable research evidence? We evaluated
      thyroid function test results of 110 healthy adults with Down syndrome to
      determine biochemical thyroid status. Approximately two thirds were biochemically
      euthyroid when assessed by standard reference ranges for the general population.
      We believe that there is a need for revalidation of "normal" thyroid function
      tests parameters when applied to the Down syndrome population and that persons
      with Down syndrome are possibly being misdiagnosed and inappropriately treated
      for a nonexistent medical disorder.

PMID- 15568964
TI  - Preattentive orienting in adolescents with mental retardation.
AB  - Visual attention is preattentively drawn to abrupt onsets of stimuli appearing in
      a visual array. In this experiment, I examined the speed of attentional capture
      for persons with and without mental retardation. Participants identified target
      stimuli that were signaled by a valid location cue (20% of the time), an invalid
      location cue (60% of the time), or no cue (20% of the time). Participants without
      mental retardation exhibited maximum influence of the cue at cue/target
      separations that were 100 msec shorter than did participants with mental
      retardation. These results indicate that processing-speed differences between
      persons with and those without mental retardation can be observed even when
      processing resources not involved in the information processing.

PMID- 15568965
TI  - Generalized reduction of problem behavior of young children with autism: building
      trans-situational interventions.
AB  - The effects of functional communication training on the generalized reduction of
      problem behavior with three 4- to 5-year-old children with autism and problem
      behavior were evaluated. Participants were assessed in primary teaching settings
      and in three secondary, generalization settings. Through baseline analysis, lower
      effort interventions in the secondary settings were documented as ineffective
      when implemented alone. Higher effort interventions incorporating functional
      communication training were documented within a multiple baseline design to
      reduce problem behavior in the primary setting, but not in secondary settings
      until the lower effort interventions were re-introduced. Results demonstrate the
      need for trans-situational interventions based on a common functional assessment
      hypothesis across settings and including intensive interventions that enhance the
      effects of lower intensity interventions.

PMID- 15568966
TI  - Prevalence of epilepsy in adults with mental retardation and related disabilities
      in primary care.
AB  - Two primary care practices were used to recruit adults with and without
      disability. Disability groups included autism, Down syndrome, cerebral palsy, and
      mental retardation. The patients without disability had an epilepsy prevalence
      rate of 1%. The prevalence of epilepsy within the disability groups was 13% for
      cerebral palsy, 13.6% for Down syndrome; 25.4% for autism, 25.5% for mental
      retardation, and 40% for adults with both cerebral palsy and mental retardation.
      During the decades of adulthood, the prevalence of epilepsy declined for those
      with cerebral palsy and mental retardation. The prevalence of epilepsy increased
      with advancing years for adults with Down syndrome, autism, and those without
      disability. Nonetheless, during each decade the prevalence of epilepsy was higher
      in all of the disability groups compared to those without disability.

PMID- 15568967
TI  - Emotional understanding in aggressive and nonaggressive individuals with mild or
      moderate mental retardation.
AB  - Deficits in emotion recognition have been linked with aggression. However, the
      ecological validity of previous studies is limited. In this study we developed
      new materials to investigate the emotion identification skills of 19 frequently
      aggressive and 15 nonaggressive adults with mental retardation. The three tasks
      included photographs of faces, individuals displaying emotional expressions in
      context, and cartoon characters in interaction. Control tasks dealt with the
      intellectual demands of each condition. Emotion identification improved with
      increasing contextual cues across both groups. Aggressive participants had
      greater difficulty labeling emotions in contextually rich photographs than their
      nonaggressive peers and were more likely to mislabel the target character's
      emotion as angry in the cartoon task. Findings have implications for models of
      aggression and clinical interventions.

PMID- 15568970
TI  - Mobile group II introns.
AB  - Mobile group II introns, found in bacterial and organellar genomes, are both
      catalytic RNAs and retrotransposable elements. They use an extraordinary mobility
      mechanism in which the excised intron RNA reverse splices directly into a DNA
      target site and is then reverse transcribed by the intron-encoded protein. After
      DNA insertion, the introns remove themselves by protein-assisted, autocatalytic
      RNA splicing, thereby minimizing host damage. Here we discuss the experimental
      basis for our current understanding of group II intron mobility mechanisms,
      beginning with genetic observations in yeast mitochondria, and culminating with a
      detailed understanding of molecular mechanisms shared by organellar and bacterial
      group II introns. We also discuss recently discovered links between group II
      intron mobility and DNA replication, new insights into group II intron evolution
      arising from bacterial genome sequencing, and the evolutionary relationship
      between group II introns and both eukaryotic spliceosomal introns and non-LTR
      retrotransposons. Finally, we describe the development of mobile group II introns
      into gene-targeting vectors, "targetrons," which have programmable target
      specificity.

PMID- 15568971
TI  - The genetics of maize evolution.
AB  - Maize and its closest wild relatives, the teosintes, differ strikingly in the
      morphology of their female inflorescences or ears. Despite their divergent
      morphologies, several studies indicate that some varieties of teosinte are
      cytologically indistinguishable from maize and capable of forming fully fertile
      hybrids with maize. Molecular analyses identified one form of teosinte (Zea mays
      ssp. parviglumis) as the progenitor of maize. Analyses of the inheritance of the
      morphological traits that distinguish maize and teosinte indicates that they are
      under the control of multiple genes and exhibit quantitative inheritance.
      Nevertheless, these analyses have also identified a few loci of large effect that
      appear to represent key innovations during maize domestication. Remaining
      challenges are to identify additional major and minor effect genes, the
      polymorphisms within these genes that control the phenotypes, and how the
      combination of the individual and epistatic effects of these genes transformed
      teosinte into maize.

PMID- 15568972
TI  - Genetic control of retrovirus susceptibility in mammalian cells.
AB  - Host cellular genes can have profound effects on retrovirus replication. Many of
      these genes encode restriction factors that block virus infection; others encode
      positive factors that are exploited by the viruses. Recently, a number of such
      genes have been cloned and characterized, bringing into sharper focus the
      mechanisms and pathways exploited by these viruses. The major host factors
      involved in the early phase of the viral life cycle are discussed.

PMID- 15568973
TI  - Light signal transduction in higher plants.
AB  - Plants utilize several families of photoreceptors to fine-tune growth and
      development over a large range of environmental conditions. The UV-A/blue light
      sensing phototropins mediate several light responses enabling optimization of
      photosynthetic yields. The initial event occurring upon photon capture is a
      conformational change of the photoreceptor that activates its protein kinase
      activity. The UV-A/blue light sensing cryptochromes and the red/far-red sensing
      phytochromes coordinately control seedling establishment, entrainment of the
      circadian clock, and the transition from vegetative to reproductive growth. In
      addition, the phytochromes control seed germination and shade-avoidance
      responses. The molecular mechanisms involved include light-regulated subcellular
      localization of the photoreceptors, a large reorganization of the transcriptional
      program, and light-regulated proteolytic degradation of several photoreceptors
      and signaling components.

PMID- 15568974
TI  - Chlamydomonas reinhardtii in the landscape of pigments.
AB  - This review focuses on the biosynthesis of pigments in the unicellular alga
      Chlamydomonas reinhardtii and their physiological and regulatory functions in the
      context of information gathered from studies of other photosynthetic organisms.
      C. reinhardtii is serving as an important model organism for studies of
      photosynthesis and the pigments associated with the photosynthetic apparatus.
      Despite extensive information pertaining to the biosynthetic pathways critical
      for making chlorophylls and carotenoids, we are just beginning to understand the
      control of these pathways, the coordination between pigment and apoprotein
      synthesis, and the interactions between the activities of these pathways and
      those for other important cellular metabolites branching from these pathways.
      Other exciting areas relating to pigment function are also emerging: the role of
      intermediates of pigment biosynthesis as messengers that coordinate metabolism in
      the chloroplast with nuclear gene activity, and the identification of
      photoreceptors and their participation in critical cellular processes including
      phototaxis, gametogenesis, and the biogenesis of the photosynthetic machinery.
      These areas of research have become especially attractive for intensive
      development with the application of potent molecular and genomic tools currently
      being applied to studies of C. reinhardtii.

PMID- 15568975
TI  - The genetics of geochemistry.
AB  - Bacteria are remarkable in their metabolic diversity due to their ability to
      harvest energy from myriad oxidation and reduction reactions. In some cases,
      their metabolisms involve redox transformations of metal(loid)s, which lead to
      the precipitation, transformation, or dissolution of minerals.
      Microorganism/mineral interactions not only affect the geochemistry of modern
      environments, but may also have contributed to shaping the near-surface
      environment of the early Earth. For example, bacterial anaerobic respiration of
      ferric iron or the toxic metalloid arsenic is well known to affect water quality
      in many parts of the world today, whereas the utilization of ferrous iron as an
      electron donor in anoxygenic photosynthesis may help explain the origin of Banded
      Iron Formations, a class of ancient sedimentary deposits. Bacterial genetics
      holds the key to understanding how these metabolisms work. Once the genes and
      gene products that catalyze geochemically relevant reactions are understood, as
      well as the conditions that trigger their expression, we may begin to predict
      when and to what extent these metabolisms influence modern geochemical cycles, as
      well as develop a basis for deciphering their origins and how organisms that
      utilized them may have altered the chemical and physical features of our planet.

PMID- 15568976
TI  - Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
AB  - Completion of the cell cycle requires the temporal and spatial coordination of
      chromosome segregation with mitotic spindle disassembly and cytokinesis. In
      budding yeast, the protein phosphatase Cdc14 is a key regulator of these late
      mitotic events. Here, we review the functions of Cdc14 and how this phosphatase
      is regulated to accomplish the coupling of mitotic processes. We also discuss the
      function and regulation of Cdc14 in other eukaryotes, emphasizing conserved
      features.

PMID- 15568977
TI  - Recombination proteins in yeast.
AB  - The process of homologous recombination promotes error-free repair of double
      strand breaks and is essential for meiosis. Central to the process of homologous
      recombination are the RAD52 group genes (RAD50, RAD51, RAD52, RAD54, RDH54/TID1,
      RAD55, RAD57, RAD59, MRE11, and XRS2), most of which were identified by their
      requirement for the repair of ionizing radiation-induced DNA damage in
      Saccharomyces cerevisiae. The Rad52 group proteins are highly conserved among
      eukaryotes. Recent studies showing defects in homologous recombination and double
      strand break repair in several human cancer-prone syndromes have emphasized the
      importance of this repair pathway in maintaining genome integrity. Herein, we
      review recent genetic, biochemical, and structural analyses of the genes and
      proteins involved in recombination.

PMID- 15568978
TI  - Developmental gene amplification and origin regulation.
AB  - Developmentally regulated gene amplification serves to increase the number of
      templates for transcription, yielding greatly increased protein and/or RNA
      product for gene(s) at the amplified loci. It is observed with genes that are
      very actively transcribed and during narrow windows of developmental time where
      copious amounts of those particular gene products are required. Amplification
      results from repeated firing of origins at a few genomic loci, while the rest of
      the genome either does not replicate, or replicates to a lesser extent. As such,
      amplification is a striking exception to the once-and-only-once rule of DNA
      replication and may be informative as to that mechanism. Drosophila amplifies
      eggshell (chorion) genes in the follicle cells of the ovary to allow for rapid
      eggshell synthesis. Sciara amplifies multiple genes in larval salivary gland
      cells that encode proteins secreted in the saliva for the pupal case. Finally,
      Tetrahymena amplifies its rRNA genes several thousand-fold in the creation of the
      transcriptionally active macronucleus. Due to the ease of molecular and genetic
      analysis with these systems, the study of origin regulation has advanced rapidly.
      Comparisons reveal an evolutionarily conserved trans-regulatory apparatus and a
      similar organization of sequence-specific cis-regulatory replicator and origin
      elements. The studies indicate a regulatory role for chromatin structure and
      transcriptionally active genes near the origins.

PMID- 15568979
TI  - The function of nuclear architecture: a genetic approach.
AB  - Eukaryotic genomes are distributed on linear chromosomes that are grouped
      together in the nucleus, an organelle separated from the cytoplasm by a
      characteristic double membrane studded with large proteinaceous pores. The
      chromatin within chromosomes has an as yet poorly characterized higher-order
      structure, but in addition to this, chromosomes and specific subchromosomal
      domains are nonrandomly positioned in nuclei. This review examines functional
      implications of the long-range organization of the genome in interphase nuclei. A
      rigorous test of the physiological importance of nuclear architecture is achieved
      by introducing mutations that compromise both structure and function. Focussing
      on such genetic approaches, we address general concepts of interphase nuclear
      order, the role of the nuclear envelope (NE) and lamins, and finally the
      importance of spatial organization for DNA replication and heritable gene
      expression.

PMID- 15568980
TI  - Genetic models in pathogenesis.
AB  - To decipher the complexity of host-pathogen interactions the widest possible
      range of model hosts and of analytical methods is required. As some virulence
      mechanisms and certain host responses have been conserved throughout evolution,
      even simple organisms can be used as model hosts to help our understanding of
      infectious diseases. The availability of molecular genetic tools and a
      cooperative community of researchers are pivotal to the emergence of model
      systems. In this review, we first summarize the genetic screens that can be used
      to identify pathogen virulence factors, then we present a comparative overview of
      existing or emerging genetically tractable host models.

PMID- 15568981
TI  - Melanocytes and the microphthalmia transcription factor network.
AB  - The first mouse microphthalmia transcription factor (Mitf ) mutation was
      discovered over 60 years ago, and since then over 24 spontaneous and induced
      mutations have been identified at the locus. Mitf encodes a member of the Myc
      supergene family of basic helix-loop-helix zipper (bHLH-Zip) transcription
      factors. Like Myc, Mitf regulates gene expression by binding to DNA as a
      homodimer or as a heterodimer with another related family member, in the case of
      Mitf the Tfe3, Tfeb, and Tfec proteins. The study of Mitf has provided many
      insights into the biology of melanocytes and helped to explain how melanocyte
      specific gene expression and signaling is regulated. The human homologue of MITF
      is mutated in patients with the pigmentary and deafness disorder Waardenburg
      Syndrome Type 2A (WS2A). The mouse Mitf mutations therefore serve as a model for
      the study of this human disease. Mutations and/or aberrant expression of several
      MITF family member genes have also been reported in human cancer, including
      melanoma (MITF), papillary renal cell carcinoma (TFE3, TFEB), and alveolar soft
      part sarcoma (TFE3). Genes in the MITF/TFE pathway may therefore also represent
      valuable therapeutic targets for the treatment of human cancer. Here we review
      recent developments in the analysis of Mitf function in vivo and in vitro and
      show how traditional genetics, modern forward genetics and in vitro biochemical
      analyses have combined to produce an intriguing story on the role and actions of
      a gene family in a living organism.

PMID- 15568982
TI  - Epigenetic regulation of cellular memory by the Polycomb and Trithorax group
      proteins.
AB  - During the development of multicellular organisms, cells become different from
      one another by changing their genetic program in response to transient stimuli.
      Long after the stimulus is gone, "cellular memory" mechanisms enable cells to
      remember their chosen fate over many cell divisions. The Polycomb and Trithorax
      groups of proteins, respectively, work to maintain repressed or active
      transcription states of developmentally important genes through many rounds of
      cell division. Here we review current ideas on the protein and DNA components of
      this transcriptional memory system and how they interact dynamically with each
      other to orchestrate cellular memory for several hundred genes.

PMID- 15568983
TI  - Repair and genetic consequences of endogenous DNA base damage in mammalian cells.
AB  - Living organisms dependent on water and oxygen for their existence face the major
      challenge of faithfully maintaining their genetic material under a constant
      attack from spontaneous hydrolysis and active oxygen species and from other
      intracellular metabolites that can modify DNA bases. Repair of endogenous DNA
      base damage by the ubiquitous base-excision repair pathway largely accounts for
      the significant turnover of DNA even in nonreplicating cells, and must be
      sufficiently accurate and efficient to preserve genome stability compatible with
      long-term cellular viability. The size of the mammalian genome has necessitated
      an increased complexity of repair and diversification of key enzymes, as revealed
      by gene knock-out mouse models. The genetic instability characteristic of cancer
      cells may be due, in part, to mutations in genes whose products normally function
      to ensure DNA integrity.

PMID- 15568984
TI  - Mitochondria of protists.
AB  - Over the past several decades, our knowledge of the origin and evolution of
      mitochondria has been greatly advanced by determination of complete mitochondrial
      genome sequences. Among the most informative mitochondrial genomes have been
      those of protists (primarily unicellular eukaryotes), some of which harbor the
      most gene-rich and most eubacteria-like mitochondrial DNAs (mtDNAs) known.
      Comparison of mtDNA sequence data has provided insights into the radically
      diverse trends in mitochondrial genome evolution exhibited by different
      phylogenetically coherent groupings of eukaryotes, and has allowed us to pinpoint
      specific protist relatives of the multicellular eukaryotic lineages (animals,
      plants, and fungi). This comparative genomics approach has also revealed unique
      and fascinating aspects of mitochondrial gene expression, highlighting the
      mitochondrion as an evolutionary playground par excellence.

PMID- 15568985
TI  - Metagenomics: genomic analysis of microbial communities.
AB  - Uncultured microorganisms comprise the majority of the planet's biological
      diversity. Microorganisms represent two of the three domains of life and contain
      vast diversity that is the product of an estimated 3.8 billion years of
      evolution. In many environments, as many as 99% of the microorganisms cannot be
      cultured by standard techniques, and the uncultured fraction includes diverse
      organisms that are only distantly related to the cultured ones. Therefore,
      culture-independent methods are essential to understand the genetic diversity,
      population structure, and ecological roles of the majority of microorganisms.
      Metagenomics, or the culture-independent genomic analysis of an assemblage of
      microorganisms, has potential to answer fundamental questions in microbial
      ecology. This review describes progress toward understanding the biology of
      uncultured Bacteria, Archaea, and viruses through metagenomic analyses.

PMID- 15568986
TI  - Genomic imprinting and kinship: how good is the evidence?
AB  - The kinship theory of genomic imprinting proposes that parent-specific gene
      expression evolves at a locus because a gene's level of expression in one
      individual has fitness effects on other individuals who have different
      probabilities of carrying the maternal and paternal alleles of the individual in
      which the gene is expressed. Therefore, natural selection favors different levels
      of expression depending on an allele's sex-of-origin in the previous generation.
      This review considers the strength of evidence in support of this hypothesis for
      imprinted genes in four "clusters," associated with the imprinted loci Igf2,
      Igf2r, callipyge, and Gnas. The clusters associated with Igf2 and Igf2r both
      contain paternally expressed transcripts that act as enhancers of prenatal growth
      and maternally expressed transcripts that act as inhibitors of prenatal growth.
      This is consistent with predictions of the kinship theory. However, the clusters
      also contain imprinted genes whose phenotypes as yet remain unexplained by the
      theory. The principal effects of imprinted genes in the callipyge and Gnas
      clusters appear to involve lipid and energy metabolism. The kinship theory
      predicts that maternally expressed transcripts will favor higher levels of
      nonshivering thermogenesis (NST) in brown adipose tissue (BAT) of animals that
      huddle for warmth as offspring. The phenotypes of reciprocal heterozygotes for
      Gnas knockouts provide provisional support for this hypothesis, as does some
      evidence from other imprinted genes (albeit more tentatively). The diverse
      effects of imprinted genes on the development of white adipose tissue (WAT) have
      so far defied a unifying hypothesis in terms of the kinship theory.

PMID- 15568987
TI  - Mechanisms of pattern formation in plant embryogenesis.
AB  - Many of the patterning mechanisms in plants were discovered while studying
      postembryonic processes and resemble mechanisms operating during animal
      development. The emergent role of the plant hormone auxin, however, seems to
      represent a plant-specific solution to multicellular patterning. This review
      summarizes our knowledge on how diverse mechanisms that were first dissected at
      the postembryonic level are now beginning to provide an understanding of plant
      embryogenesis.

PMID- 15568988
TI  - Duplication and divergence: the evolution of new genes and old ideas.
AB  - Over 35 years ago, Susumu Ohno stated that gene duplication was the single most
      important factor in evolution. He reiterated this point a few years later in
      proposing that without duplicated genes the creation of metazoans, vertebrates,
      and mammals from unicellular organisms would have been impossible. Such big leaps
      in evolution, he argued, required the creation of new gene loci with previously
      nonexistent functions. Bold statements such as these, combined with his proposal
      that at least one whole-genome duplication event facilitated the evolution of
      vertebrates, have made Ohno an icon in the literature on genome evolution.
      However, discussion on the occurrence and consequences of gene and genome
      duplication events has a much longer, and often neglected, history. Here we
      review literature dealing with the occurrence and consequences of gene
      duplication, beginning in 1911. We document conceptual and technological advances
      in gene duplication research from this early research in comparative cytology up
      to recent research on whole genomes, "transcriptomes," and "interactomes."

PMID- 15568989
TI  - Genetic analyses from ancient DNA.
AB  - About 20 years ago, DNA sequences were separately described from the quagga (a
      type of zebra) and an ancient Egyptian individual. What made these DNA sequences
      exceptional was that they were derived from 140- and 2400-year-old specimens.
      However, ancient DNA research, defined broadly as the retrieval of DNA sequences
      from museum specimens, archaeological finds, fossil remains, and other unusual
      sources of DNA, only really became feasible with the advent of techniques for the
      enzymatic amplification of specific DNA sequences. Today, reports of analyses of
      specimens hundreds, thousands, and even millions of years old are almost
      commonplace. But can all these results be believed? In this paper, we critically
      assess the state of ancient DNA research. In particular, we discuss the
      precautions and criteria necessary to ascertain to the greatest extent possible
      that results represent authentic ancient DNA sequences. We also highlight some
      significant results and areas of promising future research.

PMID- 15568990
TI  - Proteolysis as a regulatory mechanism.
AB  - Proteases can play key roles in regulation by controlling the levels of critical
      components of, for example, signal transduction pathways. Proteolytic processing
      can remove regulatory proteins when they are not needed, while transforming
      others from the dormant into the biologically active state. The latter mechanism
      often involves a subsequent change of cellular localization such as the movement
      from the membrane to the nucleus. The investigation of these processes has
      revealed a new type of proteolytic activity, regulated intramembrane proteolysis,
      and a reversible switch in activity occurring in the HtrA family of serine
      proteases. The bacterial RseA and the human amyloid precursor processing pathways
      are used as models to review these novel principles that are evolutionarily
      conserved and have wide biological implications.

PMID- 15568991
TI  - Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae.
AB  - Cells respond to a plethora of signals using a limited set of intracellular
      signal transduction components. Surprisingly, pathways that transduce distinct
      signals can share protein components, yet avoid erroneous cross-talk. A highly
      tractable model system in which to study this paradox is the yeast Saccharomyces
      cerevisiae, which harbors three mitogen-activated protein kinase (MAPK) signal
      transduction cascades that share multiple signaling components. In this review we
      first describe potential mechanisms by which specificity could be achieved by
      signaling pathways that share components. Second, we summarize key features and
      components of the yeast MAPK pathways that control the mating pheromone response,
      filamentous growth, and the response to high osmolarity. Finally, we review
      biochemical analyses in yeast of mutations that cause cross-talk between these
      three MAPK pathways and their implications for the mechanistic bases for
      signaling specificity. Although much remains to be learned, current data indicate
      that scaffolding and cross pathway inhibition play key roles in the maintenance
      of fidelity.

PMID- 15568992
TI  - rRNA transcription in Escherichia coli.
AB  - Ribosomal RNA transcription is the rate-limiting step in ribosome synthesis in
      bacteria and has been investigated intensely for over half a century. Multiple
      mechanisms ensure that rRNA synthesis rates are appropriate for the cell's
      particular growth condition. Recently, important advances have been made in our
      understanding of rRNA transcription initiation in Escherichia coli. These include
      (a) a model at the atomic level of the network of protein-DNA and protein-protein
      interactions that recruit RNA polymerase to rRNA promoters, accounting for their
      extraordinary strength; (b) discovery of the nonredundant roles of two small
      molecule effectors, ppGpp and the initiating NTP, in regulation of rRNA
      transcription initiation; and (c) identification of a new component of the
      transcription machinery, DksA, that is absolutely required for regulation of rRNA
      promoter activity. Together, these advances provide clues important for our
      molecular understanding not only of rRNA transcription, but also of transcription
      in general.

PMID- 15568993
TI  - Comparative genomic structure of prokaryotes.
AB  - Recent advances in DNA-sequencing technologies have made available an enormous
      resource of data for the study of bacterial genomes. The broad sample of complete
      genomes currently available allows us to look at variation in the gross features
      and characteristics of genomes while the detail of the sequences reveal some of
      the mechanisms by which these genomes evolve. This review aims to describe
      bacterial genome structures according to current knowledge and proposed
      hypotheses. We also describe examples where mechanisms of genome evolution have
      acted in the adaptation of bacterial species to particular niches.

PMID- 15568994
TI  - Species specificity in pollen-pistil interactions.
AB  - For pollination to succeed, pollen must carry sperm through a variety of
      different floral tissues to access the ovules within the pistil. The pistil
      provides everything the pollen requires for success in this endeavor including
      distinct guidance cues and essential nutrients that allow the pollen tube to
      traverse enormous distances along a complex path to the unfertilized ovule.
      Although the pistil is a great facilitator of pollen function, it can also be
      viewed as an elaborate barrier that shields ovules from access from inappropriate
      pollen, such as pollen from other species. Each discrete step taken by pollen
      tubes en route to the ovules is a potential barrier point to ovule access and
      waste by inappropriate mates. In this review, we survey the current molecular
      understanding of how pollination proceeds, and ask to what extent is each step
      important for mate discrimination. As this field progresses, this synthesis of
      functional biology and evolutionary studies will provide insight into the
      molecular basis of the species barriers that maintain the enormous diversity seen
      in flowering plants.

PMID- 15568995
TI  - Integration of adeno-associated virus (AAV) and recombinant AAV vectors.
AB  - The driving interest in adeno-associated virus (AAV) has been its potential as a
      gene delivery vector. The early observation that AAV can establish a latent
      infection by integrating into the host chromosome has been central to this
      interest. However, chromosomal integration is a two-edged sword, imparting on one
      hand the ability to maintain the therapeutic gene in progeny cells, and on the
      other hand, the risk of mutations that are deleterious to the host. A clearer
      understanding of the mechanism and efficiency of AAV integration, in terms of
      contributing viral and host-cell factors and circumstances, will provide a
      context in which to evaluate these potential benefits and risks. Research to date
      suggests that AAV integration in any context is inefficient, and that the
      persistence of AAV gene delivery vectors in tissues is largely attributable to
      episomal genomes.

PMID- 15568999
TI  - MSK1 activity is controlled by multiple phosphorylation sites.
AB  - MSK1 (mitogen- and stress-activated protein kinase) is a kinase activated in
      cells downstream of both the ERK1/2 (extracellular-signal-regulated kinase) and
      p38 MAPK (mitogen-activated protein kinase) cascades. In the present study, we
      show that, in addition to being phosphorylated on Thr-581 and Ser-360 by ERK1/2
      or p38, MSK1 can autophosphorylate on at least six sites: Ser-212, Ser-376, Ser
      381, Ser-750, Ser-752 and Ser-758. Of these sites, the N-terminal T-loop residue
      Ser-212 and the 'hydrophobic motif' Ser-376 are phosphorylated by the C-terminal
      kinase domain of MSK1, and their phosphorylation is essential for the catalytic
      activity of the N-terminal kinase domain of MSK1 and therefore for the
      phosphorylation of MSK1 substrates in vitro. Ser-381 is also phosphorylated by
      the C-terminal kinase domain, and mutation of Ser-381 decreases MSK1 activity,
      probably through the inhibition of Ser-376 phosphorylation. Ser-750, Ser-752 and
      Ser-758 are phosphorylated by the N-terminal kinase domain; however, their
      function is not known. The activation of MSK1 in cells therefore requires the
      activation of the ERK1/2 or p38 MAPK cascades and does not appear to require
      additional signalling inputs. This is in contrast with the closely related RSK
      (p90 ribosomal S6 kinase) proteins, whose activity requires phosphorylation by
      PDK1 (3-phosphoinositide-dependent protein kinase 1) in addition to
      phosphorylation by ERK1/2.

PMID- 15569000
TI  - Relationship of serum osteoprotegerin levels with coronary artery disease
      severity, left ventricular hypertrophy and C-reactive protein.
AB  - OPG (osteoprotegerin) is an inhibitor of osteoclastogenesis and recent work
      suggests it has a role in atherosclerosis. Therefore we measured serum OPG levels
      in patients with coronary artery disease, compared the serum OPG levels among the
      different groups according to the number of stenotic vessels and determined
      whether there was any correlation with aortic calcification, LV (left
      ventricular) mass index and serum CRP (C-reactive protein) levels. Subjects
      (n=100; mean age, 57 years) who underwent coronary angiograms were enrolled.
      Blood pressure, body mass index, fasting blood glucose, lipid profiles and CRP
      levels were measured and the LV mass indices were calculated using ECGs. Serum
      OPG levels were measured by ELISA. The presence of calcification in the aortic
      notch was checked by a chest X-ray. The subjects were divided into four groups
      according to the number of stenotic vessels. The mean serum OPG levels increased
      significantly as the number of stenotic vessels increased, and the mean serum OPG
      levels were higher in the group with three-vessel disease compared with the
      groups with no- or one-vessel disease. The mean serum CRP level was significantly
      higher in the group with three-vessel disease compared with the groups with no-,
      one- and two-vessel disease. Age and LV mass index showed significant positive
      correlations with serum OPG levels, although significance was lost after an
      adjustment for age. Serum CRP levels were positively correlated with serum OPG
      levels even after an adjustment for age. There were no differences in serum OPG
      levels according to the presence of fasting hyperglycaemia or aortic
      calcification. In conclusion, serum OPG level was related to the severity of
      stenotic coronary arteries and serum CRP levels. LV mass indices showed no
      significant correlation with OPG levels. The precise mechanism for the role of
      OPG in atherosclerosis needs to be investigated further.

PMID- 15569001
TI  - Bulgecin A: a novel inhibitor of binuclear metallo-beta-lactamases.
AB  - Bulgecin A, a sulphonated N-acetyl-D-glucosamine unit linked to a 4-hydroxy-5
      hydroxymethylproline ring by a beta-glycosidic linkage, is a novel type of
      inhibitor for binuclear metallo-beta-lactamases. Using steady-state kinetic
      analysis with nitrocefin as the beta-lactam substrate, bulgecin A competitively
      inhibited the metallo-beta-lactamase BceII from Bacillus cereus in its two-zinc
      form, but failed to inhibit when the enzyme was in the single-zinc form. The
      competitive inhibition was restored by restoring the second zinc ion. The single
      zinc metallo-beta-lactamase from Aeromonas veronii bv. sobria, ImiS, was not
      inhibited by bulgecin A. The tetrameric L1 metallo-beta-lactamase from
      Stenotrophomonas maltophilia was subject to partial non-competitive inhibition,
      which is consistent with a kinetic model in which the enzyme bound to inhibitor
      retains catalytic activity. Docking experiments support the conclusion that
      bulgecin A co-ordinates to the zinc II site in metallo-beta-lactamases via the
      terminal sulphonate group on the sugar moiety.

PMID- 15569002
TI  - Characterization of the inositol phosphorylceramide synthase activity from
      Trypanosoma cruzi.
AB  - IPC (inositol phosphorylceramide) synthase is an enzyme essential for fungal
      viability, and it is the target of potent antifungal compounds such as rustmicin
      and aureobasidin A. Similar to fungi and some other lower eukaryotes, the
      protozoan parasite Trypanosoma cruzi is capable of synthesizing free or protein
      linked glycoinositolphospholipids containing IPC. As a first step towards
      understanding the importance and mechanism of IPC synthesis in T. cruzi, we
      investigated the effects of rustmicin and aureobasidin A on the proliferation of
      different life-cycle stages of the parasite. The compounds did not interfere with
      the axenic growth of epimastigotes, but aureobasidin A decreased the release of
      trypomastigotes from infected murine peritoneal macrophages and the number of
      intracellular amastigotes in a dose-dependent manner. We have demonstrated for
      the first time that all forms of T. cruzi express an IPC synthase activity that
      is capable of transferring inositol phosphate from phosphatidylinositol to the C
      1 hydroxy group of C6-NBD-cer {6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)
      amino]hexanoylceramide} to form inositol phosphoryl-C6-NBD-cer, which was
      purified and characterized by its chromatographic behaviour on TLC and HPLC,
      sensitivity to phosphatidylinositol-specific phospholipase C and resistance to
      mild alkaline hydrolysis. Unlike the Saccharomyces cerevisiae IPC synthase, the
      T. cruzi enzyme is stimulated by Triton X-100 but not by bivalent cations, CHAPS
      or fatty-acid-free BSA, and it is not inhibited by rustmicin or aureobasidin A,
      or the two in combination. Further studies showed that aureobasidin A has effects
      on macrophages independent of the infecting T. cruzi cells. These results suggest
      that T. cruzi synthesizes its own IPC, but by a mechanism that is not affected by
      rustmicin and aureobasidin A.

PMID- 15569003
TI  - Multiple interactions of the 'transducer' govern its function in calpain
      activation by Ca2+.
AB  - Typical calpains in mammals become activated on binding of 8-12 Ca2+ ions per
      enzyme molecule, giving an example of integrated, manifold regulation by calcium.
      Besides two identified Ca2+ sites in catalytic domain II and several EF-hand
      motifs in domains IV and VI, an acidic loop in the centrally positioned domain
      III seems to harbour Ca2+. The mediator of distant Ca2+-induced structural
      transitions is an elongated structural element, the 'transducer'. By site
      directed mutagenesis along the transducer, we have generated various forms of rat
      m-calpain in which critical intramolecular interactions, as judged from the X-ray
      structure, would be abolished or modified. The kinetic parameters of these mutant
      enzymes support a model featuring shrinkage of transducer as a contributor to
      structural changes involved in calpain activation.

PMID- 15569004
TI  - Insight into the pathogenesis of sporadic basal cell carcinoma.
AB  - Sporadic basal cell carcinoma (BCC) is the commonest human cancer. Although its
      aggressiveness is low and metastatic potential negligible, the increasing
      incidence of the tumor in the Western world drives attention to its pathogenesis.
      In 1996, germ-line mutations in the patched receptor of the Sonic hedgehog (Shh)
      signaling pathway were described in the Gorlin-Goltz syndrome in association with
      multiple nevoid BCCs. Later, the aberrant activation of the Shh was identified in
      sporadic BCCs as well. Recently, the role of other tumor suppressors and DNA
      repair gene mutations and their relationship with UV radiation-induced DNA damage
      have been elucidated.

PMID- 15569005
TI  - Is human herpesvirus 7 the causative agent of pityriasis rosea?--A critical
      review.
AB  - BACKGROUND: Conflicting results on the association of pityriasis rosea and human
      herpesvirus 7 infection have been reported by different investigators. AIM: To
      review the level of evidence for such an association. METHODS: Medline was
      searched with unlimited data entry and 13 reports were retrieved. The data were
      analyzed for a causative association according to the criteria of Fredericks and
      Relman, which take into consideration latent infection and the reactivation of
      viruses characteristic of herpesviruses, and the roles of sequence-based
      detection methods. RESULTS: None of the criteria was substantiated by the
      findings of most investigators. Factors leading to the discrepancies of the
      results were discussed. CONCLUSION: There is currently insufficient evidence that
      human herpesvirus 7 infection is causally related to pityriasis rosea.

PMID- 15569006
TI  - Spectrum of autoimmune bullous diseases in Kuwait.
AB  - BACKGROUND: Autoimmune bullous diseases (ABDs) are a rare but significant group
      of dermatoses that pose great challenges to the treating dermatologist. Most
      epidemiological studies have focused on a single ABD. Few surveys have been
      carried out to describe the whole spectrum of ABDs in a region, and no such
      studies are available from the Arabian Peninsula. OBJECTIVES: To determine the
      clinico-epidemiological features of various ABDs in Kuwait, and to compare the
      results with those reported elsewhere. METHODS: A total of 128 cases of ABDs were
      studied over a span of 11.5 years. The diagnosis in all cases was confirmed by
      histopathology, and direct and indirect immunofluorescence (IMF). The diagnosis
      of various subepidermal ABDs was further confirmed by indirect IMF on salt-split
      skin (SSS) and that of pemphigus by desmoglein 1 and 3 enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Eighty seven per cent of patients were of
      Arab ethnicity. Pemphigus was observed to be the commonest ABD (47%), followed by
      pemphigoid (22%), pemphigoid gestationis (PG) (19%), linear IgA bullous disease
      (LABD) (7%), lichen planus pemphigoides (LPP) (3%), and epidermolysis bullosa
      acquisita (EBA) (2.3%). The minimum estimated incidence in the local population
      was 4.6, 2.14, 1.83, 0.69, 0.30, and 0.23 cases per million per year,
      respectively. Pemphigus patients were observed to have a younger age of onset
      (36.50 +/- 11.36 years) than reported elsewhere. BP, although the second
      commonest ABD, was less prevalent than in Europe and Singapore, and BP patients
      were observed to have a striking female predominance (85%). The prevalence of PG
      was much higher than that reported elsewhere. LABD was the fourth commonest ABD,
      and 89% of patients were children. CONCLUSIONS: The study suggests that similar
      surveys from different regions would expand our understanding of ABD.

PMID- 15569007
TI  - The clinical appearance of clonal nevi (inverted type A nevi).
AB  - BACKGROUND: The term "clonal nevus" is used to describe a variant of melanocytic
      nevus that histologically exhibits a localized proliferation of pigmented
      epithelioid dermal melanocytes within an otherwise ordinary nevus (Ball NJ,
      Golitz LE. Melanocytic nevi with focal atypical epithelioid cell components: a
      review of seventy-three cases. J Am Acad Dermatol 1994; 30: 724-729). Reports to
      date have focused on the histologic appearance of these lesions. AIM: To
      characterize the clinical appearance of clonal nevi. METHODS: Clinical and
      histologic examinations were performed of a single clonal nevus from each of five
      patients (two men and three women; age range, 37-80 years). RESULTS: All nevi
      were round to oval in shape with smooth, well-defined borders. They were
      uniformly tan to light brown in color, except for a single blue-gray to blue
      black focus of hyperpigmentation. The diameters of the nevi ranged from 2.5 to 10
      mm. In individual nevi, the hyperpigmented focus was either centrally or
      eccentrically located and measured 1-2 mm in diameter. Histologically, these
      lesions showed banal melanocytes associated with a localized proliferation of
      melanocytes with abundant pigmented cytoplasm in the dermis, admixed with
      melanophages. CONCLUSIONS: The appearance of clonal nevi--tan with a focus of
      blue-gray to blue-black pigmentation--allows one to recognize the lesion
      clinically.

PMID- 15569008
TI  - Cutaneous disease and religious practice: case of allergic contact dermatitis to
      tefillin and review of the literature.

PMID- 15569009
TI  - p16 expression in psoriatic lesions following therapy with propylthiouracil, an
      antithyroid thioureylene.
AB  - Plaque formation is a characteristic finding in patients with psoriasis and
      reflects cytokine-induced keratinocyte proliferation and/or impaired apoptosis of
      keratinocytes. Antithyroid thioureylenes such as propylthiouracil (PTU) and
      methimazole (MMI) are effective in the treatment of plaque psoriasis. Following
      PTU and MMI treatment, proliferative cell nuclear antigen (PCNA) expression is
      significantly reduced, suggesting that these medications have an
      antiproliferative effect. p16 is an antiapoptotic protein that is present in
      relative abundance in psoriatic plaques and is believed to play a potential role
      in the persistent senescence and impaired apoptosis of the keratinocytes in the
      plaque. This study examined p16 expression in biopsy samples of eight patients
      with plaque psoriasis given 300 mg of propylthiouracil in divided doses for 3
      months. Despite significant clinical and histological improvement with PTU
      treatment, p16 expression was essentially unchanged, suggesting that the
      beneficial effect of PTU in psoriasis is not mediated through a decrease in p16
      expression. The effect of PTU on other antiapoptotic proteins such as bcl-xL
      remains to be determined.

PMID- 15569010
TI  - Evidence that thalidomide modifies the immune response of patients suffering from
      actinic prurigo.
AB  - BACKGROUND: Actinic prurigo (AP) is a photodermatosis with a restricted ethnic
      distribution, mainly affecting Mestizo women (mixed Indian and European). The
      lesions are polymorphic and include macules, papules, crusts, hyperpigmentation
      and lichenification. Thalidomide, an effective immunomodulatory drug, was first
      used successfully to treat AP in 1973. In this work we describe the effect that
      thalidomide had on TNF-alpha sera levels and on IL-4- and IFN gamma (IFNgamma)
      producing lymphocytes of actinic prurigo (AP) patients. METHODS: Actinic prurigo
      patients were analyzed before and after thalidomide treatment. The percentage of
      IL-4+ or IFNgamma+ CD3+ lymphocytes was analyzed in eight of them by flow
      cytometry. TNFalpha in sera was measured by ELISA in 11 patients. RESULTS: A
      direct correlation was observed between resolution of AP lesions and an increase
      in IFNgamma+ CD3+ peripheral blood mononuclear cells (P < or = 0.001) and a
      decrease in TNFalpha serum levels (no statistical difference). No IL-4+ CD3+
      cells were detected. CONCLUSIONS: Our findings confirm that AP is a disease that
      has an immunological component and that thalidomide clinical efficacy is exerted
      not only through inhibition of TNFalpha synthesis, but also through modulation of
      INFgamma-producing CD3+ cells. These cells could be used as clinical markers for
      recovery.

PMID- 15569011
TI  - Macular amyloidosis: an assessment of prevalence, sex, and age.
AB  - Macular amyloidosis is a relatively common cutaneous disease in Asia and the
      Middle East. It is characterized by a reticulated or rippled pattern of
      pigmentation mostly in the upper back. This study was performed not only to
      determine the disease sex and age distribution, but also to evaluate its risk
      factors and the frequency among the dermatology clinic patients. Based on the
      clinical and random histopathologic findings, 100 macular amyloidosis patients
      were evaluated in a period of 3 years. Although the sex distribution (9 : 1,
      female : male ratio) differed dramatically from most of the previous reports, it
      was consistent with few other series. Eighty one percent of patients were between
      21 and 50 years of age. The mean age of the female patients was higher than that
      of the males (difference of two means was 10.26 years and P = 0.027).
      Backscatching during bathing probably is not a common practice in Iran, therefore
      we could not consider this as a risk factor in our study. We found no evidence of
      any other associated risk factors.

PMID- 15569012
TI  - Apolipoprotein E polymorphism and lipoprotein compositions in patients with
      Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a multisystemic disease of unknown etiology
      characterized by chronic relapsing oral-genital ulcers and uveitis. Some
      abnormalities in lipoprotein metabolism have been described in patients with BD.
      METHODS: In this study, apolipoprotein E (apo E) polymorphism and lipoprotein
      cholesterol concentrations in 30 patients with BD were compared with those of 27
      control subjects. RESULTS: Both patients and controls were found to be
      normolipidemic. Patients with BD had significantly higher concentrations of high
      density lipoprotein (HDL) cholesterol than those of controls (P < 0.05); however,
      there was no difference in serum triglyceride, low-density lipoprotein (LDL) and
      very low-density lipoprotein (VLDL) cholesterol concentrations. The distribution
      of apo E genotypes and alleles was the same in both groups. There were slight
      differences in allele frequency between the groups, but this was not
      statistically significant. CONCLUSIONS: The high HDL cholesterol levels observed
      in our patients were not related to abnormalities in apo E alleles.

PMID- 15569013
TI  - Urogenital myiasis caused by Psychoda albipennis (Diptera: Nematocera) in Turkey.

PMID- 15569014
TI  - Clinico-pathological study of 12 cases of patients with leprosy admitted to Sina
      Hospital, Hamadan, Iran, from 1991 to 2000.
AB  - BACKGROUND: Leprosy is considered a chronic disabling condition. Many clinical
      and immunological aspects of the disease remain ill defined. AIM: The study of
      clinico-pathological and laboratory findings of patients with leprosy admitted to
      Sina Hospital, Hamadan, Iran, from 1991 to 2000. METHODS AND PATIENTS: This is a
      descriptive retrospective cross-sectional study. The statistical community
      comprised all patients diagnosed leprosy. This diagnosis was clinical and
      confirmed through pathology (skin-biopsy) and laboratory (peripheral smear)
      measures. RESULTS: In this study, the disease was more common in males than
      females with a mean age of 48.5 +/- 16.2 years. Most of the patients were more
      than 40 years old. Among 12 patients in this study, six cases were urban and six
      cases were rural. Six cases were living in Hamadan province and two cases
      migrated to Hamadan province (one of them from Afghanistan and the other from
      Kurdestan). Clinical diagnosis was confirmed by pathology in 11 cases, but in one
      case the clinical diagnosis did not match the pathology. In four cases the
      clinical diagnosis did not match the peripheral smear. Eight cases were admitted
      just once. Four cases had a history of recurrence and readmission (two patients
      had one time recurrence and the other two patients had two recurrences). There
      was no difference in the clinical findings between first presentation and
      recurrence. From the point of complication and disability, extremity disability
      was more common than eye disability. Increased severity of complications was
      found in patients with a delayed diagnosis and incomplete treatment. CONCLUSION:
      This study showed that a rapid and correct diagnosis and complete treatment was
      necessary for prevention of complication and disability in patients with leprosy.
      Also the accuracy of pathology (skin biopsy) in the diagnosis exceeded the
      peripheral smear. Skin biopsy is recommended to confirm the diagnosis in all
      cases of leprosy. In the absence of pathology, patients must be considered as
      multibacillary patients and treated as such.

PMID- 15569015
TI  - Pigmentary demarcation lines in a pregnant Caucasian woman.

PMID- 15569016
TI  - Facial porokeratosis characterized by destructive lesions.
AB  - Porokeratosis is a rare group of keratinizing diseases. It is inherited as an
      autosomal dominant disease with variable penetrance, although sporadic cases are
      often reported. Porokeratosis has as its histological hallmark the typical
      cornoid lamella. Porokeratosis lesions localized on the face can vary from
      superficial to destructive in nature. Only 12 cases have been reported in the
      literature to date. We report one more unusual case of destructive facial
      porokeratosis.

PMID- 15569018
TI  - Angioma serpiginosum: a case report.

PMID- 15569019
TI  - Alopecia totalis incognito.

PMID- 15569020
TI  - Telangiectasia macularis eruptiva perstans with an associated myeloproliferative
      disorder.
AB  - Telangiectasia macularis eruptiva perstans (TMEP) is a cutaneous form of
      mastocytosis. It has been rarely associated with an underlying myeloproliferative
      disorder. We report the case of a patient, while receiving treatment for
      thrombocytosis, with both platelet production and function inhibitors presented
      with TMEP. TMEP is often refractory to therapy; however, our patient responded to
      treatment with PUVA.

PMID- 15569021
TI  - Thermosensitive lichen amyloidosis.
AB  - BACKGROUND: A 26-year-old male presented with a 3-year history of lichen
      amyloidosis. On examination, there was a pigmented papular eruption with a ripple
      pattern affecting the limbs and trunk but sparing the axillae, antecubital and
      popliteal fossae, central chest, neck and face. There was also prominent sparing
      of the skin overlying the superficial veins of the limbs. The sparing of the
      superficial veins of the limbs by lichen amyloidosis raised the possible role of
      cutaneous temperature in governing the distribution of amyloid deposits in our
      patient. OBSERVATIONS: Total body infrared thermography demonstrated consistent
      sparing of the amyloid deposits in areas with higher cutaneous temperatures such
      as the neck and axillae as well as the course of the superficial veins. The
      cooler areas such as the extensor surfaces of the arms and legs corresponded to
      areas of amyloid deposition. Narrow band ultraviolet B (NBUVB) phototherapy over
      a 5-month period resulted in a marked improvement of pruritus and clearing of the
      amyloid deposits. CONCLUSIONS: Our patient clearly demonstrated lichen
      amyloidosis in a thermosensitive distribution. This may be a gross manifestation
      of previous reports of in vitro thermosensitivity of amyloid fibril formation and
      may have potential implications in treatment at least in a subset of patients
      demonstrating this clinical feature.

PMID- 15569022
TI  - Pressure alopecia.

PMID- 15569023
TI  - Acquired localized cutis laxa confined to the face: case report and review of the
      literature.
AB  - BACKGROUND: Cutis laxa is an uncommon entity characterized by laxity of the skin,
      which hangs in loose folds, producing the appearance of premature aging. It can
      be subdivided into congenital and acquired. This latter variant is rare and the
      skin involvement varies from generalized to localized. We report a case of a
      localized acquired cutis laxa confined to the face, without preceding
      inflammatory lesions or systemic compromise. Four similar cases have been
      reported to date. The etiology remains unknown and there is no definitive
      treatment. METHODS: A 27-year-old White woman came to our hospital with a
      wrinkled face, pendulous earlobes and drop eyelids. Changes began 5 years prior,
      and she appeared much older than her age. RESULTS: Histological analysis and
      ultrastructural examination of skin biopsy revealed reduction and fragmentation
      of elastic fibers, confirming the diagnosis of cutis laxa. No systemic
      involvement was diagnosed. The patient was submitted to plastic surgery for
      repair, with satisfactory results to date. CONCLUSIONS: Acquired localized cutis
      laxa confined to the face without preceding inflammatory lesions is extremely
      rare. The etiology remains unknown. Clinical features and histopathologic
      findings confirm the diagnosis. Surgical repair seems to be the only therapeutic
      choice, but the results are variable and temporary.

PMID- 15569024
TI  - Giant cutaneous melanoacanthoma.

PMID- 15569025
TI  - Sweet's syndrome associated with Staphylococcus aureus.

PMID- 15569026
TI  - Contact sensitivity to aluminum.

PMID- 15569027
TI  - Florid eruption of seborrheic keratoses associated with elevated insulin-like
      growth factor, hypoglycemia, and solitary fibrous tumor of the pleura.

PMID- 15569028
TI  - Keratosis lichenoides chronica.

PMID- 15569029
TI  - Follicular mucinosis in a 4-year-old boy.

PMID- 15569030
TI  - Milia in regressing plaques of mycosis fungoides: provoked by topical nitrogen
      mustard or not?
AB  - OBJECTIVE: To report three cases of mycosis fungoides with milia formation in the
      regressing lesions. PATIENTS AND SETTING: Dermatology clinic of a university
      hospital (referral center). Three patients with mycosis fungoides with body
      surface involvement of 10% in one case (stage IIb) and exceeding 30% in two cases
      (stages IIb and III). All patients were treated with photochemotherapy and
      topical nitrogen mustard ointment in a concentration of 0.01%. After
      approximately 3 months multiple milia erupted on regressing plaques. RESULTS: The
      presence of milia was evident and was confirmed by histopathology. Regression of
      mycosis fungoides was noted in these plaques both clinically and in comparison
      with the pretreatment histologic appearance. Two of the patients showed a
      histological picture of follicular mucinosis. CONCLUSIONS: We do not know the
      significance of milia in mycosis fungoides (MF). However, we suggest that
      follicular rupture or a degenerative process might result in milia formation.

PMID- 15569031
TI  - Lichen nitidus after hepatitis B vaccine.

PMID- 15569032
TI  - Cutaneous vascular malformation associated with osteolysis or Gorham's sign.

PMID- 15569033
TI  - Disseminated granuloma annulare accompanying mycobacterium tuberculosis
      lymphadenitis.

PMID- 15569034
TI  - Papular elastolytic giant cell granuloma responding to hydroxychloroquine and
      quinacrine.

PMID- 15569035
TI  - Surgical pearl: the safety pin as a better alternative to the versatile paper
      clip comedo extractor.
AB  - Acne vulgaris is a very common, chronic inflammatory disease of the pilosebaceous
      apparatus. The comedo extractor is the instrument primarily used for comedo
      extraction. There are many types of more costly instruments available, but
      extraction can be achieved with the help of a modified versatile paper clip and
      disposable syringes. The disposable syringe is a good option for acne surgery,
      but a safety pin has been found to be more effective than the clip comedo
      extractor for extracting the comedo. The safety pin can be regarded as a "two-in
      one" instrument for piercing the lesion and for extracting the keratinous
      material from the pilosebaceous canals.

PMID- 15569036
TI  - Treatment of plantar hyperhidrosis with botulinum toxin type A.
AB  - BACKGROUND: Hyperhidrosis (excessive, uncontrollable sweating) can be
      embarrassing and disabling, significantly impacting social and professional
      performance and quality of life. Treatments aim to reduce sweating, but few are
      effective, often carrying the risk of significant side-effects. The aims of this
      study were to evaluate the efficacy and safety of botulinum toxin type A (BTX-A)
      for plantar hyperhidrosis and to investigate the role of the Dermojet as a
      potential injection technique. METHODS: Ten adult patients (five men, five
      women), aged 19-51 years, with severe, previously unresponsive, plantar
      hyperhidrosis, were recruited to this single-center, open-label, noncomparative
      study. The hyperhidrotic area of each foot was injected over 15-20 sites without
      analgesia with 50 U BTX-A + 5 mL sterile saline using a Dermojet. Patients were
      followed up for 8 months with monthly sweat reduction assessments using Minor's
      iodine-starch test. Patients provided a treatment self-assessment after
      completion of follow-up. RESULTS: Within 7 days post-treatment, eight patients
      reported significantly decreased sweating, and seven patients were symptom free
      for up to 5 months. Patient self-assessment showed that seven of the 10 patients
      were satisfied with their treatment. One minor adverse event was reported
      comprising a temporary localized hematoma (one patient). CONCLUSIONS:
      Intracutaneous BTX-A injection using the Dermojet offers a simple, safe, and
      effective alternative for treatment of plantar hyperhidrosis.

PMID- 15569037
TI  - Endogenous opioids, mu-opiate receptors and chloroquine-induced pruritus: a
      double-blind comparison of naltrexone and promethazine in patients with malaria
      fever who have an established history of generalized chloroquine-induced itching.
AB  - AIMS: Chloroquine induces a severe generalized pruritus, in predisposed Black
      African patients, during treatment of malaria fever, and also in some Caucasian
      patients treated for rheumatological diseases. We have previously shown that
      chloroquine may release endogenous opioids and/or interact with micro-opiate
      receptors in rats, and that both histamine and malaria parasite blood density,
      contribute to the itching severity in malaria fever in humans. The aim of our
      present study was to assess and compare the antipruritic efficacy of the micro
      opiate receptor antagonist, naltrexone, and the antihistamine, promethazine, in
      chloroquine treated patients with malaria fever. METHODS: A double-blind,
      randomized, parallel group comparison of the chloroquine-induced pruritus
      intensity and time profile in patients with parasitologically proven malaria
      fever, who were pretreated with a single dose of either naltrexone 50 mg or
      promethazine 25 mg orally (six patients each). All patients had an established
      history of severe pruritus following chloroquine treatment of malaria fever. A
      self-assessed itching severity score was undertaken at 0, 6, 12, 24, 48 and 72 h
      after initial chloroquine dosing, and the areas under the pruritus-intensity time
      curve AUCP0-72 h was determined in each patient and correlated to the malaria
      parasite density in blood. RESULTS: Both naltrexone and promethazine subjectively
      reduced itching severity compared with prior historical experience. One patient
      on naltrexone and two on promethazine never experienced any itching. There was no
      statistically significant treatment effect, but a significant time effect (P =
      0.001, F = 4.77 d.f. 5) by two-way repeated measures ANOVA. The AUCP for
      naltrexone was 82 +/- 25 units/h, and 57 +/- 34 units/h for promethazine [95%
      confidence interval for the difference being -73 to 123]. However, the malaria
      parasite density in the naltrexone group (740 +/- 178 microl(-1)) tended to be
      higher than in the promethazine group 314 +/- 69 microl(-1) (P = 0.056, 95%
      confidence interval for the difference being -15 to 866 microl(-1)). Correction
      of the AUCP for malaria parasite density (parasite pruritogenic index, AUCP.
      units/h/parasites/microl blood) tended to be lower with naltrexone 9.1 +/- 2.6
      than with promethazine 12.2 +/- 7.0 There was a highly significant and positive
      correlation between the malaria parasite density and the AUCP0-72 h, on
      naltrexone (r2 = 0.78, P = 0.040) and promethazine (r2 = 0.93, P = 0.008).
      However, comparison of regressions revealed that the slope of the regression was
      significantly steeper with promethazine 0.48 than naltrexone 0.12 (P = 0.006, t =
      4.2), with the intercepts showing a trend to a difference (P = 0.086).
      CONCLUSION: Naltrexone exerted an antipruritic action, at least to a similar
      extent to promethazine in patients with chloroquine-induced itching in malaria
      fever. However, the relationship between parasite density and resultant pruritus
      was significantly different between naltrexone and promethazine. Thus, micro
      opiate receptors/and or endogenous opioids may contribute to chloroquine itching
      in malaria fever, in humans, in accord with animal experimental findings. Malaria
      parasite density in blood is a strong determinant of itching severity in patients
      predisposed to chloroquine-induced pruritus.

PMID- 15569038
TI  - Effect of pimecrolimus cream 1% on the long-term course of pediatric atopic
      dermatitis.
AB  - BACKGROUND: This report investigates the effect of pimecrolimus cream 1% (Elidel,
      Novartis pharma AG, Basel, Switzerland), a nonsteroid, cell-selective, cytokine
      inhibitor on the course of atopic dermatitis (AD), as assessed by changes in body
      surface involvement and pattern of drug use over time. METHODS: Data from 961
      patients in two 1-year double-blind, multicenter, pediatric studies of similar
      design were analyzed: 250 infants (aged 3-23 months) were randomized 4 : 1 and
      711 children (aged 2-17 years) were randomized 2 : 1 to receive pimecrolimus
      cream 1% or vehicle, respectively. Emollients were used by all patients to
      alleviate dry skin and, at the first signs or symptoms of AD, pimecrolimus or
      vehicle was applied twice daily to prevent progression to flares. If flares
      occurred in either group, moderately potent topical corticosteroids were
      mandated. RESULTS: Pimecrolimus was applied for 68.4% (infants) and 53.8%
      (children) of study days, and frequency of use of pimecrolimus decreased over
      time, reflecting improvement in disease control. The mean total body surface area
      affected decreased continuously over time. Significantly more patients in the
      pimecrolimus than control groups were maintained without corticosteroid therapy
      (infants: 63.7% vs. 34.8%, P < 0.001; children: 57.4% vs. 31.6%, P < 0.001,
      respectively). CONCLUSION: The need for pimecrolimus therapy decreases over time
      as the patients' disease improves. Hence, once long-term management of AD with
      pimecrolimus is established, the burden of disease for both the patient and the
      caregiver decreases significantly and disease-free periods become more frequent.

PMID- 15569040
TI  - Prayer marks.

PMID- 15569041
TI  - Segmental lichen planus.

PMID- 15569045
TI  - An update on the neuropathology of HIV in the HAART era.
AB  - This review compares the neuropathology of highly active antiretroviral therapy
      (HAART)-treated HIV+ individuals with the reported central nervous system (CNS)
      findings from the pre-HAART era. HAART has had considerable success in combating
      HIV-related immune collapse and has prevented many of the former end-stage
      complications of AIDS. However, with increased survival times the prevalence of
      minor HIV-associated cognitive impairment appears to be rising among treated
      patients and this may be a particular risk for older individuals. HIV
      encephalitis (HIVE) is still prevalent in treated patients although attenuated
      forms of HIVE and CNS opportunistic disorders are also observed. Some subjects
      show very significant CNS lymphocytic infiltrates in the context of HAART-induced
      immune reconstitution. HIV-associated cognitive impairment correlates best with
      the increased presence of activated, though not necessarily infected, microglia
      and CNS macrophages. This suggests that indirect mechanisms of neuronal injury
      and loss occur in HIV/AIDS as a basis for dementia since neurones are not
      themselves productively infected. Research to elucidate the mechanisms of
      neuronal injury in HIV/AIDS may contribute to the understanding of CNS function
      not only in HAART-treated subjects but also in other neurodegenerative disorders.

PMID- 15569046
TI  - Altered patterns of the interferon-inducible gene IFI16 expression in head and
      neck squamous cell carcinoma: immunohistochemical study including correlation
      with retinoblastoma protein, human papillomavirus infection and proliferation
      index.
AB  - AIMS: To investigate whether the expression of interferon (IFN)-inducible gene
      IFI16 is inversely related to proliferative activity in vivo, we compared
      immunohistochemical reactivity of IFI16 in a series of head and neck squamous
      cell carcinomas (HNSCCs) with their proliferation index and the cell cycle
      regulator pRb. As human papillomavirus (HPV) infection is manifested by changes
      in the function or expression level of host genes such as IFN-inducible genes, we
      also investigated the presence of HPV DNA to determine whether head and neck
      cancers associated with HPV DNA can be distinguished from tumours that are
      presumably transformed by other mechanisms. METHODS: Thirty-six HNSCCs were
      evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The
      presence of HPV was also detected by polymerase chain reaction. Nine tumours were
      located in the oropharynx (tonsillar area) and 27 in the larynx. RESULTS: HPV DNA
      was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar
      SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade
      IFI16 expression. Overall, proliferative activity was significantly related to
      tumour differentiation and histological grading. IFI16 protein expression was
      significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating
      tumours positive for IFI16 staining showed a marked expression of pRb and a
      better prognosis than those whose tumours had low IFI16, pRb levels and a high
      proliferation index. CONCLUSIONS: To our knowledge, this is the first expression
      analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours
      positive for IFI16 staining showed a marked expression of pRb and a better
      prognosis than those whose tumours had low IFI16, pRb levels and a high
      proliferation index.

PMID- 15569047
TI  - Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma:
      evidence for its odontogenic epithelial differentiation.
AB  - AIMS: Adamantinomatous craniopharyngioma (ACP) resembles histologically some
      odontogenic tumours, such as ameloblastoma and calcifying odontogenic cyst.
      However, there has been no evidence that ACP differentiates also functionally as
      odontogenic epithelium. The aim of this study was to gain evidence of odontogenic
      epithelial differentiation in ACP by means of immunohistochemistry. Among normal
      human tissues, enamel proteins are expressed exclusively in teeth, and lymphoid
      enhancer factor 1 (LEF1), in co-operation with beta-catenin, play an important
      role in tooth development. The expression of these proteins is therefore
      indicative of odontogenic epithelial differentiation. METHODS AND RESULTS: The
      expression of enamel proteins and LEF1 was examined in 10 adamantinomatous and
      six papillary craniopharyngiomas. All the ACPs showed a variable degree of enamel
      protein expression, including amelogenin, enamelin and enamelysin, mainly in
      ghost cells. LEF1 was also heterogeneously expressed in ACPs; remarkably, its
      expression pattern was identical to that of nuclear beta-catenin accumulation. In
      contrast, none of the papillary craniopharyngiomas expressed enamel proteins or
      LEF1. CONCLUSIONS: These results suggest that ACP consistently shows odontogenic
      epithelial differentiation. Since ACPs harbour beta-catenin mutation, the
      inappropriate activation of beta-catenin/LEF1 complex-dependent transcription may
      play a critical role in ACP tumorigenesis.

PMID- 15569048
TI  - Relationship between micropapillary component and micrometastasis in the regional
      lymph nodes of patients with stage I lung adenocarcinoma.
AB  - AIMS: To determine whether a micropapillary component is a prognostic predictor,
      with particular reference to nodal micrometastasis, in patients with stage I lung
      adenocarcinomas. METHODS AND RESULTS: Thirty-five cases with stage I lung
      adenocarcinomas, obtained from lobectomies or pneumonectomies, and 434 dissected
      hilar and mediastinal lymph nodes, were retrospectively reviewed. A
      micropapillary component and nodal micrometastasis were found in 16 (45.7%) and
      14 (40%) of the 35 cases, respectively, with nodal micrometastasis in 24 (5.5%)
      of the 434 lymph nodes, in an immunohistochemical study using an anti-cytokeratin
      antibody. Ten (62.5%) of the 16 cases with a micropapillary component, and four
      (21.1%) of the remaining 19 cases, showed nodal micrometastases (P = 0.014).
      Kaplan-Meier survival curves demonstrated that there was no significant
      difference between the cases with and without a micropapillary component (P =
      0.28). However, the 5 years' survival of the cases with and without nodal
      micrometastases were 71.4% and 35.7%, respectively (P = 0.03). CONCLUSIONS: A
      micropapillary component may be a manifestation of aggressive behaviour, as shown
      by frequent micrometastasis, for stage I lung adenocarcinomas.

PMID- 15569049
TI  - Polymerized alpha-antitrypsin is present on lung vascular endothelium. New
      insights into the biological significance of alpha-antitrypsin polymerization.
AB  - AIMS: The damage to lung tissue in chronic obstructive pulmonary disease (COPD)
      may involve the progressive loss of pulmonary vascular endothelial cells.
      Endothelial binding of alpha1-antitrypsin (alpha1-AT) derived from plasma has
      been identified, and alpha1-AT deficiency is a known genetic risk factor
      associated with alpha1-AT polymerization and COPD development. Therefore, in the
      present study we aimed to investigate if alpha1-AT is present on the lung
      vascular endothelium, and if it is in a polymeric form. METHODS AND RESULTS:
      Postmortem paraffin-embedded tissue specimens from 15 COPD (chronic bronchitis
      and emphysema) cases with and without Z alpha1-AT (Glu342Lys) deficiency and from
      10 cases without signs of COPD were studied. Immunohistochemistry was performed
      using the streptavidin-biotin method with a monoclonal ATZ11 antibody specific
      for polymeric alpha1-AT, and polyclonal antibodies against human alpha1-AT and
      neutrophil elastase. Vascular endothelium showed intense staining for alpha1-AT
      with the ATZ11 antibody in all cases; however, intensity of staining in patients
      with alpha1-AT deficiency was greater. No endothelial staining was observed with
      the anti-elastase antibody. CONCLUSIONS: This is the first demonstration that
      alpha1-AT bound to the vascular endothelium of lungs is in a polymeric form,
      which also suggests a possible previously unknown role for polymeric alpha1-AT in
      vivo.

PMID- 15569050
TI  - Chromophobe renal cell carcinoma: a comparative study of histological,
      immunohistochemical and ultrastructural features using high throughput tissue
      microarray.
AB  - AIMS: In some cases distinction between chromophobe renal cell carcinoma (CRCC),
      oncocytoma and clear cell (conventional) renal cell carcinoma (eosinophilic
      variant) using routine light microscopy remains problematic. The present study
      investigates the level of agreement in the diagnosis of CRCC, as well as the
      histological features most frequently used for this diagnosis by two pathologists
      with a special interest in renal neoplasia. The sensitivity and specificity of
      immunohistochemical markers in cases with overlapping histological features in
      the diagnosis of CRCC were also studied. Electron microscopy was performed, as a
      diagnostic gold standard, on all of the cases. METHODS AND RESULTS: Thirty-two
      renal tumours with predominantly eosinophilic cytoplasm were reviewed in a
      blinded fashion by two pathologists. The diagnosis and morphological features
      used to render each diagnosis were tabulated. Validation of the utility of
      keratin 7 and 20, epithelial membrane antigen (EMA), vimentin, CD10, parvalbumin,
      RCC antigen, antimitochondrial antibody and Hale's colloidal iron was performed
      by the construction of a tissue microarray (TMA) master block. Based on
      histological criteria alone, overall agreement on the diagnosis of these tumours
      was reached in 69% of the cases, while there was total disagreement in 12%. In
      59% of the cases, total agreement was reached in classifying the case as a CRCC
      based on histology alone. Kappa statistics for interobserver variability were
      calculated as only slight agreement (kappa = 0.3). The histological features most
      frequently associated with a diagnosis of CRCC were accentuated cell borders
      (87%) and a combination of hyperchromatic wrinkled nuclei (79%) and perinuclear
      halos (74%). The most sensitive and specific marker for CRCC was parvalbumin
      (sensitivity 0.91; specificity 1.0). The immunohistochemical profile of EMA+/
      vimentin- was useful but had low specificity (sensitivity 0.75; specificity 0.4).
      CD10 had the highest sensitivity (1.0) but worst specificity (0.25) for CRCC.
      Keratin 7 had high sensitivity (0.83) but fairly low specificity (0.37) for CRCC.
      Hale's colloidal iron and the RCC antigen marker were not contributory. Finally,
      the antimitochondrial antibody was found to be fairly sensitive (0.83) for
      excluding CRCC. CONCLUSIONS: A small but significant proportion of renal tumours
      with cells having eosinophilic cytoplasm cannot be classified, even by
      experienced pathologists, based on histology alone. In these cases it is
      imperative to use markers with known sensitivity and specificity for the
      diagnosis of CRCC.

PMID- 15569051
TI  - Comparative analysis of COX-2, vascular endothelial growth factor and microvessel
      density in human renal cell carcinomas.
AB  - AIMS: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are
      frequently up-regulated in malignant tumours and play a role in proliferation,
      apoptosis, angiogenesis and tumour invasion. In the present study, the expression
      of COX-2 and VEGF in renal cell carcinoma (RCC) was analysed and correlated with
      the microvessel density (MVD). METHODS AND RESULTS: COX-2 and VEGF were analysed
      by realtime reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. The MVD was assessed by CD31 immunohistochemistry. The
      expression of COX-2 and VEGF was determined in the RCC cell lines A498 and Caki-1
      under short-term hypoxia and in multicellular tumour cell aggregates. COX-2 was
      expressed in RCC by tumour epithelia, endothelia and macrophages in areas of
      cystic tumour regression and tumour necrosis. COX-2 protein in RCC was not
      altered in comparison with normal renal tissue. VEGF mRNA was up-regulated in RCC
      and positively correlated with MVD. RCC with high up-regulation of VEGF mRNA
      showed weak intracytoplasmic expression of VEGF in tumour cells. Intracytoplasmic
      VEGF protein expression was negatively correlated with MVD. In RCC with necrosis
      the MVD was reduced in comparison with RCC without necrosis. A498 RCC cells down
      regulated COX-2 and up-regulated VEGF under conditions of hypoxia. In Caki-1
      cells COX-2 expression remained stable, whereas VEGF was significantly up
      regulated. In multicellular A498 cell aggregates COX-2 and VEGF were up-regulated
      centrally, whereas no gradient was found in Caki-1 cells. CONCLUSIONS: COX-2 and
      VEGF are potential therapeutic targets because COX-2 and VEGF are expressed in
      RCC and associated cell populations such as endothelia and monocytes/macrophages.

PMID- 15569052
TI  - High microvascular density is correlated with high VEGF, iNOS and COX-2
      expression in penetrating growth-type early gastric carcinomas.
AB  - AIMS: Early gastric carcinomas have two characteristic growth types, superficial
      spreading (SUP) and penetrating (PEN). Higher mucosal apoptotic activity and
      lower p21(WAF1/CIP1) expression and submucosal low proliferative activity have
      been shown in the former, compared with the latter. In order to cast light on
      whether angiogenesis contributes to these growth patterns, the present
      immunohistochemical study was performed with cancer tissues. METHODS AND RESULTS:
      Of a total of 807 early gastric carcinomas, 30 PEN and 33 SUP type submucosal
      invasive carcinoma cases were immunohistochemically compared. CD34 positivity,
      microvascular density (MVD), and expression of vascular endothelial growth factor
      (VEGF) and inducible nitric oxide synthase (iNOS), but not cyclooxygenase 2 (COX
      2) were higher in cancer cells in both mucosal and submucosal layers in PEN than
      in SUP (P < 0.05). Submucosal MVD in PEN type was greater (P < 0.01) in cases
      with high than with low Ki67 labelling. Significant correlations were shown
      between MVD and VEGF, iNOS and COX-2, and VEGF and iNOS expression in the PEN
      type, but only a weak correlation between iNOS and COX-2 expression was evident
      with the SUP type. CONCLUSIONS: Increased MVD in PEN type has an intimate causal
      relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type,
      in contrast, has characteristics of low angiogenesis.

PMID- 15569053
TI  - CD23 expression in mediastinal large B-cell lymphomas.
AB  - AIMS: Mediastinal large B-cell lymphoma (MLBCL) is a subtype of diffuse large B
      cell lymphoma (DLBCL) in the WHO classification with peculiar features, such as
      female prevalence, young patient age and bulky presentation. It shows a B-cell
      phenotype with variable expression of surface immunoglobulin, negative CD21 and
      CD10 and positive CD30 in a large number of cases. An origin from activated
      thymic B cells has been suggested in several studies. A subpopulation of large,
      dendritic cells (asteroid cells) strongly expressing CD23 has been identified
      amongst thymic B cells and these could represent the normal cellular counterpart
      for this type of primary mediastinal large cell lymphoma. METHODS AND RESULTS: To
      explore this possibility, we immunostained 24 cases of primary mediastinal
      lymphomas and 100 cases of non-mediastinal, nodal and extranodal, DLBCLs for CD23
      in routinely processed paraffin-embedded tissues. CONCLUSIONS: Our results show
      that a vast majority (70%) of mediastinal lymphomas strongly express CD23 whilst
      the same antigen is expressed in only 15% of non-mediastinal nodal DLBCLs and 9%
      of non-mediastinal extranodal DLBCLs. These results support the hypothesis that
      most cases of MLBCL arise from activated dendritic thymic B cells. We also
      suggest that CD23 should be included in the panel of antibodies currently used to
      characterize this subtype of DLBCL.

PMID- 15569054
TI  - Immunohistochemical characterization of endometrial leucocytes in endometritis.
AB  - AIMS: Leucocytes are a normal and variable component of the endometrial stromal
      cell population. The aim of this study was to characterize endometrial leucocytes
      in established cases of endometritis in order to determine whether there are
      objective characteristics of the leucocyte infiltrate which would allow its
      identification as part of an inflammatory process rather then the normal
      physiological leucocyte infiltrate. METHODS AND RESULTS: We examined endometrial
      tissue from 79 cases of endometritis and 22 histologically normal controls.
      Leucocytes were characterized immunohistochemically for CD45, CD20, CD68, CD3 and
      CD56 and numbers were analysed semiquantitatively on a scale of 0-4. In many
      endometritis cases the overall number of leucocytes was increased. Furthermore,
      leucocytes were unusually distributed with a tendency to accumulate superficially
      beneath the endometrial surface. Whilst numbers of macrophages, T lymphocytes and
      endometrial granulated lymphocytes (uterine natural killer cells) did not differ
      between endometritis samples and controls, most endometritis cases contained a
      substantially increased number of B cells, which normally represent 1% or less of
      the endometrial leucocyte population. B lymphocytes were also observed in unusual
      locations such as intraepithelially and within glandular lumina. CONCLUSIONS:
      These results suggest that immunohistochemical characterization of endometrial
      leucocytes may be helpful in establishing a diagnosis of endometritis in
      equivocal cases.

PMID- 15569055
TI  - Presence of nanobacteria in psammoma bodies of ovarian cancer: evidence for
      pathogenetic role in intratumoral biomineralization.
AB  - AIMS: The presence of laminated, calcified extracellular debris known as psammoma
      bodies is a well-known histomorphological feature of ovarian adenocarcinomas and
      other human malignancies. Biomineralization has recently been found to be
      associated with a group of extremely small Gram-negative bacteria capable of
      precipitating calcium salts. The aim of the present study was to evaluate a
      possible pathogenic link between the development of psammoma bodies and
      nanobacteria infection. MATERIAL AND RESULTS: Immunohistochemical staining and
      reverse transcriptase-polymerase chain reaction (RT-PCR) were used to analyse
      nanobacterial protein and gene expression in eight psammona body-containing
      adenocarcinomas and in 10 malignant ovarian tumours without signs of
      biomineralization. Nanobacterial proteins were detected in eight out of eight
      (100%) psammoma-positive tumour samples. Conversely, none of the 10 psammoma
      negative tissues (0%) was positive for nanobacterial antigens. Furthermore,
      nanobacterial mRNA was detectable in all of the four tissues (100%) that
      contained psammoma bodies, but was absent in all 10 ovarian cystadenocarcinomas
      (0%) that were psammoma negative. CONCLUSIONS: We found a 100% concordance
      between the expression of nanobacteria and the presence of psammoma bodies in
      malignant ovarian tumours. Several lines of evidence suggest the involvement of
      these organisms in the process of biomineralization. We therefore conclude that
      nanobacterial infection of malignant ovarian tissue contributes to mechanisms
      leading to the formation of calcified deposits known as psammoma bodies.

PMID- 15569056
TI  - Histiocytic infiltration in ulcerative colitis, simulating malignancy.

PMID- 15569058
TI  - Familial adenomatous polyposis associated with colon carcinoma, desmoid tumour,
      gallbladder carcinoma, and endometrioid carcinoma: a case report.

PMID- 15569059
TI  - Familial pleural mesothelioma with environmental asbestos exposure: losses of DNA
      sequences by comparative genomic hybridization (CGH).

PMID- 15569060
TI  - Primary acinic cell carcinoma of the breast: a case report with long-term follow
      up and review of the literature.

PMID- 15569061
TI  - IgA nephropathy complicating graft-versus-host disease, another nephropathy
      causing nephrotic syndrome after bone marrow transplantation.

PMID- 15569062
TI  - Primary peripheral PNET/Ewing's sarcoma of the dura with FISH analysis.

PMID- 15569063
TI  - Primary low-grade B-cell lymphoma of the endometrium.

PMID- 15569065
TI  - Inactivation of Gram-negative and Gram-positive bacteria in red cell concentrates
      using INACTINE PEN110 chemistry.
AB  - BACKGROUND AND OBJECTIVES: The risk of transfusion-transmitted bacterial
      infections as a result of the presence of bacteria in blood is one of the major
      concerns in transfusion medicine. The purpose of this study was to investigate
      whether bacteria inoculated into red blood cell concentrates can be inactivated
      by the INACTINE PEN110 pathogen-reduction process. Four bacterial species were
      chosen for the study: anaerobic Gram-positive Clostridium perfringens and
      Propionibacterium acnes, known to be transfusion-transmitted; and two Gram
      negative species, Acinetobacter johnsonii and Acinetobacter lwoffii, recently
      reported to be a common cause of transfusion-associated infections in Europe.
      MATERIALS AND METHODS: Identical units of leucoreduced red cell concentrates were
      inoculated with A. johnsonii, A. lwoffii, C. perfringens, or P. acnes. The 4
      degrees C control units were put on storage immediately after receiving the
      spike. The test units were subjected to PEN110 treatment and then stored. The
      bacterial titre in all units was monitored during a 6-week storage period.
      RESULTS: The PEN110 inactivation of all tested bacterial strains was time- and
      titre-dependent. For A. johnsonii and A. lwoffii, no viable bacteria were
      detected in the units spiked with up to 10(4) colony-forming units (CFU)/ml and
      treated with PEN110. For red cell units spiked with 10(4)-10(5) CFU/ml of C.
      perfringens and P. acnes, no viable bacteria were detected in the units treated
      with PEN110. In control units, there was a gradual decrease in A. johnsonii, A.
      lwoffii and C. perfringens titres during cold storage, while P. acnes titres
      remained stable. CONCLUSIONS: The PEN110 pathogen-reduction process was
      demonstrated to inactivate high titres of A. johnsonii, A. lwoffii, C.
      perfringens and P. acnes in red cell concentrates.

PMID- 15569066
TI  - Evaluation of a malarial antibody assay for use in the screening of blood and
      tissue products for clinical use.
AB  - BACKGROUND AND OBJECTIVES: A new recombinant Plasmodium antigen enzyme
      immunoassay (EIA) for the detection of malarial antibodies was evaluated for the
      screening of 'malaria-risk' blood and tissue donations. MATERIALS AND METHODS: A
      total of 13,269 donor and patient samples were tested by both the EIA and the
      standard diagnostic antibody immunofluorescence test (IFAT). RESULTS: A total of
      114/138 (82.6%) samples from patients with P. falciparum and 11/13 (84.6%)
      samples from patients with P. vivax tested positive. A total of 714/13,053
      (5.47%) samples from donors identified as 'malaria risk', owing to residency or
      travel, were reactive in the EIA. CONCLUSIONS: The assay is more sensitive than a
      previously implemented malarial antibody EIA (73% in acute P. falciparum and 56%
      in acute P. vivax infections). The sensitivity of this new EIA is comparable to
      that of the IFAT, and the specificity is sufficient to screen 'malaria-risk'
      donors.

PMID- 15569067
TI  - Effects of extended storage of whole blood before leucocyte depletion on
      coagulation factors in plasma.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the quality of
      leucocyte-depleted plasma produced from leucocyte-depleted whole blood, stored
      for different periods of times before filtration through polyurethane filters.
      MATERIALS AND METHODS: Whole blood was collected, from 48 voluntary donors, into
      quadruple blood bag sets with integrated whole-blood filters, and stored at room
      temperature for 1, 2, 6, or 18 h before filtration. Five samples were taken: one
      directly from the donor; one immediately after collection; one before and one
      after filtration; and one from plasma units before freezing. All samples were
      analysed for the following parameters: prothrombin time; activated partial
      thromboplastin time; prothrombin fragments F1+2; fibrinogen; factors VIII, XI and
      XII; von Willebrand factor antigen; ristocetin cofactor activity; collagen
      binding capacity; multimers; and complement C3a-desArg. RESULTS: Different whole
      blood storage times before filtration did not have a significant effect on the
      stability of coagulation factors. The activity of all investigated coagulation
      factors in plasma was generally above 90 U/dl, even after 18 h of storage of
      whole blood before filtration. von Willebrand factor multimeric distribution
      remained stable throughout the process. However, activation of complement did
      occur during storage. CONCLUSIONS: Leucodepleted plasma originating from
      leucodepleted whole blood maintains a satisfactory level of coagulation factors,
      even after the storage of whole blood for 18 h at room temperature before
      filtration.

PMID- 15569068
TI  - Washing of cord blood grafts after thawing: high cell recovery using an automated
      and closed system.
AB  - BACKGROUND AND OBJECTIVES: Cord blood (CB) progenitor cells are an alternative
      source of haematopoietic stem cells for bone marrow reconstitution. The critical
      importance of cell dose in the clinical outcome has motivated the need to develop
      techniques aimed at reducing cell losses and increasing reproducibility. This aim
      of this study was to evaluate an automated CB washing protocol of thawed cord
      blood units using the Sepax device. MATERIALS AND METHODS: After an initial 1:1
      dilution using a dextran/albumin-containing buffer, the cells were washed in
      order to obtain a final product ready for transplantation. The automatic method
      was compared with the conventional manual washing procedure. Blood samples were
      taken after thawing and after washing. The processing time, viability and mean
      recovery of nucleated cells (TNC) and progenitors were determined. RESULTS: The
      automatic procedure resulted in a median recovery of 93% CD34+ cells and 89% TNC;
      no significant differences were observed between methods. In addition, median
      viability, as assessed by annexin V and 7-aminoactinomycin D (7-AAD), was 98% and
      94%, respectively, within CD34+ cells. CONCLUSIONS: The automatic washing method
      described is as effective as the manual method in terms of viability and
      progenitor cells recovery, but faster and easier for the operators to perform.
      Overall, our data suggest that the automatic method is safe and suitable for the
      routine washing of thawed CB grafts in the clinic.

PMID- 15569069
TI  - Leucodepletion leads to component-like storage stability of whole blood-
      suggesting its homologous use?
AB  - BACKGROUND AND OBJECTIVES: Leucodepleted whole blood (LWB) is already widely used
      for autologous donations and could also be appropriate for certain instances of
      allogeneic transfusion provided that storage quality can be preserved at
      component-like levels. MATERIALS AND METHODS: Sixteen units of whole blood (WB),
      donated by healthy volunteers into CPDA-1 according to German guidelines, were
      leucofiltered prestorage and stored for up to 49 days. Unfiltered WB in CPDA-1
      (UFWB, n=16) and filtered red blood cells in SAGM (RCC, n=14) served as controls.
      Several haematological, biochemical and coagulatory quality parameters were
      determined at designated time-points during storage. RESULTS: Apart from
      significant differences (P<0.05) in haematocrit (56.2+/-3.6 vs. 37.9+/-3.9%), and
      in the plasma concentrations of free haemoglobin (93.1+/-37.8 vs. 57.8+/-24.3
      g/dl), K+ (38.9+/-5.3 vs. 31.5+/-4.3 mm) and ATP (2.7+/-0.2 vs. 1.6+/-0.4
      micromol/g haemoglobin), with higher levels detected in RCC, no remarkable
      differences (P>0.05) were observed regarding haemolysis (0.23+/-0.07% vs. 0.31+/
      0.13) and pH value (6.63+/-0.03 vs. 6.62+/-0.02) between RCC and LWB at the end
      of storage. Lack of leucodepletion manifested in significantly (P<0.05) higher
      rates of haemolysis (0.44+/-0.21%), free haemoglobin (89.6+/-43.5 g/dl) and lower
      pH values (6.56+/-0.04). During 42 days of LWB storage, sufficient amounts (% of
      the initial mean value) were observed with stable (factor XI, 97.5+/-15.0) and
      labile (factor V, 92.9+/-18.0; factor VIII, 69.2+/-17.1) clotting factors and
      inhibitors (antithrombin III 88.9+/-9.5), without any signs of activated
      coagulation. CONCLUSIONS: Our data indicate that the quality of LWB is comparable
      to that of components during 42 days of storage. Thus, LWB could be an
      interesting option for using to facilitate and economize the blood supply,
      especially for surgical or trauma patients.

PMID- 15569070
TI  - Stability of coagulation factors in thawed, solvent/detergent-treated plasma
      during storage at 4 degrees C for 6 days.
AB  - BACKGROUND AND OBJECTIVES: Transfusion of fresh-frozen plasma is still a pillar
      in emergency medicine for using to prevent dilutional coagulopathy or
      disseminated intravascular coagulation after severe blood loss, but thawing
      procedures can delay its availability. On the other hand, the wastage of plasma,
      once thawed and not transfused within a defined time-period, represents an
      inefficient handling of economic resources and is contradictory to blood donor
      intentions. In this study we investigated the stability of coagulation factor
      activities and plasma protein levels during 6 days of storage of thawed
      solvent/detergent (S/D)-treated plasma at +4 degrees C. Our results may form the
      basis for reconsideration of expiry times of thawed S/D-treated plasma. MATERIALS
      AND METHODS: Five units of S/D-treated plasma (Octaplas) were thawed and warmed
      to 20 degrees C, then recooled and stored at +4 degrees C for 6 days. The
      activities of coagulation factors II, V, VII, VIII, IX, X, XI and XII,
      fibrinogen, antithrombin (AT), protein C, protein S and von Willebrand factor
      antigen (vWF:Ag) were measured on days 0, 1, 2, 3 and 6. RESULTS: Except for
      protein S, the activities of all coagulation factors and inhibitors were at least
      0.5 U/ml during storage at 4 degrees C for 6 days. The mean levels, during
      storage, of factors IX, X, XI and XII, vWF:Ag, fibrinogen and protein C were at
      least 94%, and of factors II, V and VIII, and AT at least 78%, of the levels
      immediately after thawing; the activity of factor VII decreased to 83% and of
      protein S to 43% of the baseline values. CONCLUSIONS: Thawed S/D-treated plasma
      stored at +4 degrees C for up to 6 days still contains sufficient coagulation
      activities and plasma proteins to be regarded as suitable for transfusion in the
      established indications.

PMID- 15569071
TI  - A novel B(var) allele (547 G>A) demonstrates differential expression depending on
      the co-inherited ABO allele.
AB  - BACKGROUND AND OBJECTIVES: Genetic analysis of group B donors in Korea was
      performed. MATERIALS AND METHODS: Exons 6 and 7 were sequenced in 12
      phenotypically B3 donors 6 B3, 6 A1B3. RESULTS: Consensus sequences all B3 and
      2/6 A1B3 donors were present. Four A1B3 donors demonstrated a novel B allele,
      B(var), in the context of A101/ or A102/B(var) genotypes. Family studies based on
      an A1B3 donor with the B(var) allele and on another unrelated subject with
      identical genotype and phenotype revealed B(var)/O01 genotypes with full B
      antigen expression. CONCLUSIONS: B(var) allele is subject to differential
      expression, depending on the co-inherited ABO allele.

PMID- 15569072
TI  - A novel FY allele in Brazilians.
AB  - The GATA box single nucleotide polymorphism (SNP) at position -33 (T>C) in Blacks
      silences the expression of FY*B in erythrocytes, and the substitution 265 C>T,
      together with 298 G>A, weakens the Fy(b) antigen (Fy(x)). Individuals with these
      phenotypes/genotypes who receive Fy(b+) blood are unlikely to be alloimmunized to
      Fy(b) because, in the presence of 265 T, the Fy(b) antigen is expressed, and in
      the case of -33 C, other tissues express Duffy protein and probably the Fy(b)
      antigen. We studied samples from 361 blood donors (182 of African ancestry and
      179 of Caucasian ancestry) by haemagglutination and polymerase chain reaction
      (PCR) restriction fragment length polymorphism (RFLP). Forty Caucasian and 130
      donors of African ancestry were serologically Fy(b-); among these, the majority
      of the donors of African ancestry had FY*B with the GATA SNP, while the majority
      of Caucasians typing Fy(b-) had FY*B with 265 T/298 A SNPs. Six of the Fy(b-)
      donors (three Africans and three Caucasians) had both GATA and 265/298 SNPs, and
      six donors of Caucasian ancestry apparently had a GATA SNP. Samples from two
      donors - one African and one Caucasian with an unusual MspA1I-RFLP pattern - were
      sequenced and found to have a novel SNP (145 G>T) co-existent with 265 C>T and
      298 G>A SNPs. These findings highlight the importance of establishing the
      incidence and nature of molecular events that impact on Duffy expression in
      different populations.

PMID- 15569073
TI  - The platelet count accuracy of platelet concentrates obtained by using automated
      analysis is influenced by instrument bias and activated platelet components.
AB  - BACKGROUND AND OBJECTIVES: The blood platelet content (in numbers) of platelet
      concentrates is required for production quality control and to predict clinical
      responses. MATERIALS AND METHODS: This study compared the performance of
      automated counting from impedance and optical instruments to data from
      immunoplatelet reference analysis. RESULTS: All methods showed good linearity
      with evidence of significant instrument-specific deviations from the line of
      agreement. Relational formulae largely corrected bias, but did not resolve
      platelet count variability. A second confounding factor, related to the
      proportion of small (activated) platelets, was also shown to contribute to
      intermethod discrepancies. CONCLUSIONS: Blood processing centres should establish
      correction factors for each instrument compared to reference methods, such as the
      immunoplatelet count.

PMID- 15569074
TI  - Chagas' disease: application of TESA-blot in inconclusive sera from a Brazilian
      blood bank.
AB  - BACKGROUND AND OBJECTIVES: The procedure used for screening Trypanosoma cruzi
      infected blood donors by using two serological techniques has frequently led to
      discordant results. The TESA-blot, a confirmatory test for Chagas' disease, was
      applied in a survey of inconclusive sera from a Brazilian blood bank. MATERIALS
      AND METHODS: Four hundred and forty-eight sera, obtained from blood donors at the
      HRU-Fundacao Hemominas, were tested by using the TESA-blot assay, a Western
      blotting method. Of these 448 sera, 348 had previously been determined as
      inconclusive for Chagas' disease owing to discordance between the indirect
      immunofluorescence assay (IFA) and the enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The TESA-blot was positive for 2.87% (10/348) of the inconclusive sera,
      and 100% positive and negative for the sera from chagasic (n=50) and non-chagasic
      (n=50) donors, respectively. CONCLUSIONS: Our results clearly indicate the need
      to improve the diagnosis of Chagas' disease in blood banks by using new
      confirmatory diagnostic test(s). The TESA-blot, a new test with trypomastigote
      fractions of the T. cruzi Y strain, has made new approaches to the confirmation
      of Chagas' disease possible.

PMID- 15569075
TI  - Haemolytic disease of the newborn caused by anti-MUT (MNS 35).

PMID- 15569091
TI  - Red cell transfusions and blood groups.

PMID- 15569093
TI  - Ageing, oxidative stress, and mitochondrial uncoupling.
AB  - Mitochondria are a cell's single greatest source of reactive oxygen species.
      Reactive oxygen species are important for many life sustaining processes of cells
      and tissues, but they can also induce cell damage and death. If their production
      and levels within cells is not effectively controlled, then the detrimental
      effects of oxidative stress can accumulate. Oxidative stress is widely thought to
      underpin many ageing processes, and the oxidative stress theory of ageing is one
      of the most widely acknowledged theories of ageing. As well as being the major
      source of reactive oxygen species, mitochondria are also a major site of
      oxidative damage. The purpose of this review is a concise and current review of
      the effects of oxidative stress and ageing on mitochondrial function. Emphasis is
      placed upon the roles of mitochondrial proton leak, the uncoupling proteins, and
      the anti-ageing effects of caloric restriction.

PMID- 15569094
TI  - Ageing and subcellular distribution of mitochondria: role of mitochondrial DNA
      deletions and energy production.
AB  - The rapid growing population of elderly illustrates the importance of
      understanding the mechanisms responsible for ageing and the detrimental effects
      on health associated with increasing age. One of the primary mechanisms may be
      because of the accumulation of mtDNA damage and oxidative damage with age.
      Previous studies have examined this correlation in post-mitotic tissues such as
      skeletal muscle, heart and brain with decreased mitochondrial function, such as
      enzymatic activities of the electron transport chain and ATP production. However,
      regional differences in the subcellular location of mitochondria exist and most
      studies have failed to differentiate the effects of these two autonomous
      fractions, the subsarcolemmal and intermyofibrillar populations. Hence, while
      future research attempts to explain the mechanisms responsible for ageing in the
      mitochondrion, it should also take into account the independent pathways of these
      two distinctly different populations.

PMID- 15569095
TI  - Mitochondrial dysfunction measured in vivo.
AB  - AIMS: Mitochondria are responsible for meeting the majority of the energetic
      demand of most tissues. They also play a major role in regulating cell survival.
      These dual roles of mitochondria place them at the centre of many pathologies
      leading to tissue degeneration and disruption of energy balance. The prominent
      role of mitochondria in ageing and disease has led to a tremendous growth in
      mitochondrial research at the cellular and molecular level. We describe below a
      new non-invasive approach to measure mitochondrial function that will bridge the
      gap between our understanding of mitochondrial function in vitro and that in the
      intact organism. METHODS AND RESULTS: This approach uses optical and magnetic
      resonance spectroscopy to measure in vivo O2 consumption and ATP synthesis rates,
      respectively, from skeletal muscle. These values lead to a quantitative
      assessment of the mitochondrial ATP/O2 or P/O. The P/O represents the efficiency
      of coupling between phosphorylation and oxygen consumption in the mitochondria,
      which is a measure of mitochondrial dysfunction. CONCLUSIONS: This work
      represents a significant advance in research on the role of mitochondria in
      degenerative disease and ageing because it allows a quantitative measure of
      mitochondrial pathology in vivo. The non-invasive nature of this approach also
      enables repeated measures of mitochondrial function on the same individual,
      thereby making this a potentially useful diagnostic technique. The results from
      this work have led to insights into the coupling of ATP synthesis to oxidation
      and the regulation of oxidative phosphorylation by intracellular PO2.

PMID- 15569096
TI  - The behaviour of the flow-mediated brachial artery vasodilatation during
      orthostatic stress in normal man.
AB  - AIMS: Flow-mediated brachial artery vasodilatation is an index of endothelial
      function. Published literature describes only supine data and no study has been
      performed during vertical displacement. This subject deserves investigation for
      two main reasons: humans spend the larger part of their life in the upright
      position; this position has significant effects on neural vascular regulation.
      METHODS: In 21 healthy men (25 +/- 2 years) the flow-dependent brachial artery
      vasodilating response to distal circulatory arrest was assessed by Doppler
      ultrasound imaging, while supine and during 20 degrees and 60 degrees head-up
      tilting (HUT). In 11 of these subjects the vasodilating response to
      nitroglycerine was also explored. RESULTS: Absolute and percentage increments in
      brachial calibre during hyperaemia after deflation of the occluding cuff became
      increasingly greater at 20 degrees (+0.44 mm) and 60 degrees (+0.92 mm) HUT (P <
      0.01), compared with the horizontal position (+0.27 mm), and the arterial
      dilatation for an increase in flow (0.98 +/- 0.08 and 1.68 +/- 0.06 mm mL(-1)
      min(-1) x 1000, respectively) was larger (P < 0.01) than occurred while supine
      (0.41 +/- 0.05 mm mL(-1) min(-1) x 1000). Nitroglycerine-mediated vasodilatation
      at 60 degrees HUT was similar to that in the supine position. CONCLUSION: The
      orthostatic stimulus is associated with an increase of the flow-mediated brachial
      artery vasodilatation, which is proportional to the degree of displacement. The
      mechanism of this effect does not consist of changes in nitric oxide sensitivity.

PMID- 15569097
TI  - Hypotonic stress activates an intermediate conductance K+ channel in human
      colonic crypt cells.
AB  - AIM: To investigate the effect of hypotonic stress on human colonic crypts cells
      in terms of ion channel activity and intracellular Ca2+ concentration. METHODS:
      Single crypts were isolated from biopsies taken during colonoscopy. The patch
      clamp technique was used (in the cell-attached mode) to observe the activity of
      ion channels during hypotonic stress. Calcium measurements were made using the
      fluophores Fluo 3 or 4. RESULTS: The intermediate conductance (29 pS), Ca2+ 
      sensitive, K+ channel (also known as KCNN4) previously described (Sandle et al.
      1994) was seen in 54 of 149 patches (36%) when the crypts were bathed in normal
      extracellular solution (290 mOsm kg(-1)). Forty-one patches could be used for
      further analysis. Activation of one or several 29 pS channels was seen in 15 of
      41 patches (39%) after 30 s to 4 min of exposure to hypotonic solution (160 mOsm
      kg(-1)). The open probability increased from 0.0043 in control solution to 0.44
      at 5 min of hypotonic stress. When the crypts were exposed to hypotonic solution,
      an increase in intracellular Ca2+ could be seen. The increase in intracellular
      Ca2+ emanates mainly from intracellular stores. CONCLUSION: The 29 pS K+ channel
      takes part in volume regulation in human colonic crypt cells. The activation of
      this channel is mediated through an increase in intracellular Ca2+.

PMID- 15569098
TI  - Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline
      concentration in growth hormone transgenic mice.
AB  - AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have
      both been associated with alterations in autonomic nervous system function. The
      aim of this study was to investigate autonomic nervous system influence on heart
      rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR
      variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6
      months) female bGH and control mice using telemetry. HR control was studied using
      antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline
      was measured in plasma, heart and kidney using high performance liquid
      chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and
      control mice. After saline injection and after muscarinic blockade with
      methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice
      compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated
      decrease in HR from around 550 to 300-350 beats min(-1), not different between
      bGH and control mice. Time- and frequency-domain measures of HRV were reduced in
      old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were
      reduced by 25-49% in plasma and tissue of bGH compared with control mice (P <
      0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR
      in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic
      tone, reducing sympathetic nervous system function possibly via reduced
      noradrenaline stores.

PMID- 15569099
TI  - Interstitial muscle lactate, pyruvate and potassium dynamics in the trapezius
      muscle during repetitive low-force arm movements, measured with microdialysis.
AB  - AIM: Local muscle metabolic responses to repetitive low-force contractions and to
      intense static contractions were studied by microdialysis in humans. METHODS:
      Microdialysate and electromyography (EMG) were sampled from the trapezius muscle,
      mixed venous blood samples were taken and perceived exertion was rated (0-9)
      before and during 20 min of standardized repetitive arm movement (REP), 60 min
      recovery (R1), and 10 min 90 degrees sustained arm position (SUS) at 20% maximum
      voluntary contraction, followed by 60 min recovery (R2) in six healthy male
      participants (28-33 years). RESULTS: Average muscle activity was 8 +/- 2% of
      EMGmax-RMS (mean +/-SEM) during REP and 22 +/- 5% of EMGmax-RMS during SUS.
      Perceived exertion increased from 0 to 3.2 +/- 0.5 during REP and from 0 to 8.5
      +/- 0.3 during SUS. During REP interstitial muscle lactate increased from 2.1 +/-
      0.2 to 2.9 +/- 0.2 mmol L(-1) (P < 0.001) and returned to the baseline level
      during R1, while dialysate [K+] increased from 3.8 +/- 0.2 to 4.7 +/- 0.2 mmol L(
      1) (P < 0.002) and returned to 3.8 +/- 0.2 mmol L(-1) during R1. In contrast,
      plasma lactate and [K+] remained unchanged. During SUS interstitial muscle
      lactate increased from 2.3 +/- 0.2 to 3.3 +/- 0.3 mmol L(-1) (P < 0.003),
      increased further to 6.5 +/- 1.3 mmol L(-1) post-exercise (P < 0.001) and
      returned to baseline levels during R2. Dialysate [K+] increased from 3.9 +/- 0.2
      to 4.6 +/- 0.2 mmol L(-1) (P < 0.05) and returned to baseline level during R2.
      Plasma lactate increased significantly during SUS whereas plasma [K+] was
      unchanged. During REP and SUS interstitial pyruvate was unchanged but increased
      in the post-exercise period proportional to the exercise intensity. CONCLUSIONS:
      The microdialysis technique was effective in revealing muscle metabolic events
      that were not found systemically. Furthermore, the trapezius muscle showed an
      anaerobic metabolism during low-force contraction, which could indicate
      inhomogeneous muscle activation.

PMID- 15569100
TI  - Role of neuronal nitric oxide synthase in response to hypertonic saline loading
      in rats.
AB  - AIMS: This study analyses the influence of neuronal nitric oxide synthase (nNOS)
      blockade with 7-nitroindazole (7NI) on the haemodynamic and renal response to a
      hypertonic saline load (HSL). We also evaluated the effects of non-specific NOS
      inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). METHODS: The following
      groups were used: controls, rats treated with 7NI at 0.5 or 5 mg kg(-1), and rats
      treated with L-NAME at 0.5 or 5 mg kg(-1). A further five groups received an
      isotonic saline load (ISL). RESULTS: Mean arterial pressure (MAP) was
      significantly increased in control rats after HSL. MAP was further increased in
      both 7NI-treated groups, and the L-NAME groups showed marked dose-related pressor
      responses. During ISL, MAP was only significantly increased in the group treated
      with 5 mg kg(-1) of L-NAME. The pressure-natriuresis relationship during the
      experimental period after the HSL was reduced in the 7NI group treated with 5 mg
      kg(-1) and severely attenuated in both L-NAME groups. The increase in plasma
      sodium was significantly greater after the HSL in both 7NI groups and both L-NAME
      groups compared with controls. CONCLUSIONS: The present results suggest that nNOS
      and other NOS isozymes play a counter-regulatory role in the pressor response to
      HSL. Moreover, the blockade of nNOS with the higher dose of 7NI produces a
      blunted pressure-natriuresis relationship in response to the HSL. Finally, it is
      concluded that nNOS participates in the homeostatic cardiovascular and renal
      response to hypertonic saline loading by attenuating the blood pressure increase
      and hypernatremia, and facilitating natriuresis.

PMID- 15569101
TI  - Review article: current status of liver transplantation in HIV-infected patients.
AB  - The increases in survival of patients infected with human immunodeficiency virus
      is attributed to the introduction of combination human immunodeficiency virus
      antiviral therapy, better known as highly active anti-retroviral therapy. In
      fact, survival statistics have improved such that individuals often succumb to
      other disease entities, notably liver failure and not from acquired
      immunodeficiency syndrome complications. Liver transplantation has been
      introduction in this patient population in several centres around the world. This
      review will discuss the current clinical status of liver transplantation in
      individuals suffering from human immunodeficiency virus infection.

PMID- 15569102
TI  - Review article: 13C-urea breath test in the diagnosis of Helicobacter pylori
      infection -- a critical review.
AB  - The urea breath test is a non-invasive, simple and safe test which provides
      excellent accuracy both for the initial diagnosis of Helicobacter pylori
      infection and for the confirmation of its eradication after treatment. Some
      studies have found no differences between urea breath test performed under non
      fasting conditions. The simplicity, good tolerance and economy of the citric acid
      test meal probably make its systematic use advisable. The urea breath test
      protocol may be performed with relatively low doses (<100 mg) of urea: 75 mg or
      even 50 mg seem to be sufficient. With the most widely used protocol (with citric
      acid and 75 mg of urea), excellent accuracy is obtained when breath samples are
      collected as early as 10-15 min after urea ingestion. A unique and generally
      proposed cut-off level is not possible because it has to be adapted to different
      factors, such as the test meal, the dose and type of urea, or the pre-/post
      treatment setting. Fortunately, because positive and negative urea breath test
      results tend to cluster outside of the range between 2 and 5 per thousand, a
      change in cut-off value within this range would be expected to have little effect
      on clinical accuracy of the test.

PMID- 15569103
TI  - Review article: orofacial granulomatosis.
AB  - Orofacial granulomatosis is an uncommon clinicopathological entity describing
      patients who have oral lesions characterized by persistent and/or recurrent
      labial enlargement, oral ulcers and a variety of other orofacial features, who on
      lesional biopsy have lymphoedema and non-caseating granulomas. The aetiology of
      oral lesions with non-caseating granulomas includes oral Crohn's disease (some
      patients with oral lesions will develop typical bowel symptoms of Crohn's disease
      in ensuing months to years), tooth-associated infections, sarcoidosis and food or
      contact allergies. Treatment of orofacial granulomatosis is not reliably
      effective and may not be always necessary, although most patients do require some
      medical intervention.

PMID- 15569104
TI  - Review article: is there a link between micronutrient malnutrition and
      Helicobacter pylori infection?
AB  - Helicobacter pylori causes a chronic gastric infection, which is usually life
      long. Many epidemiological studies have shown that this is probably one of the
      most common bacterial infections throughout the world involving 30% of the
      population living in developed countries and up to 80-90% of the population in
      developing regions. Concomitantly, developing regions also have high prevalence
      of micronutrient malnutrition. In the last few years, some studies have suggested
      that H. pylori infection may affect the homeostasis of different micronutrients
      including iron, vitamin B12, folic acid, alpha-tocopherol, vitamin C and beta
      carotene. In this article, we discuss the current scientific information of the
      effect that H. pylori infection may produce on micronutrient malnutrition.

PMID- 15569105
TI  - Systematic review: is ingestion of paracetamol or non-steroidal anti-inflammatory
      drugs associated with exacerbations of inflammatory bowel disease?
AB  - AIM: To examine the published evidence on the association between paracetamol or
      non-steroidal anti-inflammatory drugs and relapse in inflammatory bowel disease.
      METHODS: Medline searches were performed till June 2004 and Embase till April
      2003. Abstracts published in Gut and Gastroenterology from 1999 to 2004 were hand
      searched. Twenty-nine relevant abstracts and papers were identified. RESULTS:
      Twenty-two patients with relapse of inflammatory bowel disease following exposure
      to non-steroidal anti-inflammatory drugs have been described in case-reports.
      Four patients were re-exposed to non-steroidal anti-inflammatory drugs and
      relapsed again. Two had relapsed after taking a cyclo-oxygenase 2 inhibitor. One
      study described increased inflammatory activity and clinical relapse in some
      patients after challenge with naproxen or nabumetone. Fifteen epidemiological
      studies were identified. All had small sample sizes and many had methodological
      problems. Six studies found evidence for an association between non-steroidal
      anti-inflammatory drug use and relapse of inflammatory bowel disease, but the
      association was significant in only two. Three studies suggested a relationship
      between paracetamol use and exacerbations of inflammatory bowel disease.
      CONCLUSIONS: Non-steroidal anti-inflammatory drugs may precipitate a relapse in
      some patients with inflammatory bowel disease. This may be an idiosyncratic
      reaction. The published evidence does not support the view that non-steroidal
      anti-inflammatory drugs are important in inducing relapse of inflammatory bowel
      disease. There is weak evidence that paracetamol may be more important.

PMID- 15569106
TI  - Meta-analysis: the diagnostic value of alarm symptoms for upper gastrointestinal
      malignancy.
AB  - BACKGROUND: With the advent of empirical treatment strategies for patients with
      dyspeptic symptoms, it becomes increasingly important to select patients with a
      high risk of having cancer for immediate endoscopy. Usually alarming symptoms are
      used for this matter, but their diagnostic value is by no means clear. AIM: To
      investigate the diagnostic value of alarm symptoms for upper gastrointestinal
      malignancy. METHODS: Meta-analysis of studies describing prevalence of alarm
      symptoms in patients with and without endoscopically verified upper
      gastrointestinal malignancy were identified through a Medline search. The
      prevalence, pooled sensitivity, specificity, positive and negative predictive
      values were calculated. RESULTS: About 17 case studies and nine cohort studies
      were selected. The mean prevalence of gastrointestinal malignancies in the cohort
      studies was 2.8% of 16,161 patients. Five cohort studies indicated that 25% of
      the patients diagnosed with upper gastrointestinal malignancy had no alarm
      symptoms. The pooled sensitivities of individual alarm symptoms varied from 9 to
      41%, the pooled positive predictive value ranged from 4.6 to 7.9%, and was 5.9%
      for 'having any alarm symptom'. The pooled negative predictive value was 99.4%
      for 'having any alarm symptom'. CONCLUSION: The risk of upper gastrointestinal
      malignancy in any individual without alarm symptoms is very low, but
      approximately one in four patients with upper gastrointestinal cancer have no
      alarm symptoms at the time of diagnosis.

PMID- 15569107
TI  - Meta-analysis: the effect of age on immunological response to hepatitis B vaccine
      in end-stage renal disease.
AB  - BACKGROUND: Patients on maintenance dialysis typically show a suboptimal immune
      response to hepatitis B virus vaccine compared with the non-uraemic population. A
      variety of inherited or acquired factors have been implicated in this diminished
      response. Age-associated changes in immune status may contribute to decreased
      vaccine efficacy in older individuals although contradictory results have been
      reported in individuals with normal kidney function. AIMS: To evaluate the
      relationship between age and immune response to hepatitis B vaccine in patients
      with end-stage renal disease by performing a systematic review of the literature
      with a meta-analysis of clinical trials. METHOD: We used the random effects model
      of DerSimonian and Laird; sources of heterogeneity in effect estimates were
      explored by performing sensitivity analyses. RESULTS: We identified 17 clinical
      trials (1800 unique patients); six (35%) were controlled studies. Pooling of
      study results demonstrated a significantly decreased risk of response to
      hepatitis B vaccine among older dialysis patients (overall risk ratio: 0.74; 95%
      confidence intervals: 0.70-0.79). The P-value was 0.0139 for our test of study
      heterogeneity. A lowered risk of response to hepatitis B vaccine persisted after
      exclusion of trials based on plasma-derived vaccines; it was present even when
      'older' individuals were defined as being as 50 years (RR: 0.85, 95% CI: 0.75
      0.96) or more (cut-off 60 years RR: 0.75; 95% CI: 0.66-0.85). An effect of age on
      seroprotection rate was present in all clinical reports, irrespective of the
      geographic origin of the study group: Europe (RR: 0.76; 95% CI: 0.70-0.83) North
      America (RR: 0.67; 95% CI: 0.60-0.74) or other countries (RR: 0.83; 95% CI: 0.71
      0.97). Additional doses of vaccine did not appear to have an impact on RR of
      response by age. CONCLUSIONS: Our meta-analysis showed a clear association
      between older age and impaired response to hepatitis B virus vaccine in end-stage
      renal disease patients. Such a relationship is biologically plausible.
      Vaccination schedules with adapted vaccine doses and frequent serum testing for
      loss of immunity against hepatitis B virus are recommended in elderly patients on
      maintenance dialysis.

PMID- 15569108
TI  - Meta-analysis: the detection of pancreatic malignancy with positron emission
      tomography.
AB  - BACKGROUND: Several factors contribute to the high mortality of pancreatic
      cancer, including limitations of diagnostic imaging. AIM: To perform a meta
      analysis to assess the diagnostic accuracy of Fluro-deoxy-glucose positron
      emission tomography with computed tomography compared with computed tomography
      alone. METHODS: Articles were identified through a MEDLINE search and
      bibliography review. Summary estimates and receiver operating curves were
      calculated using Meta-Test 0.6. Publication bias and heterogeneity were assessed
      with a funnel plot and chi-squared test. RESULTS: The summary estimate and 95%
      confidence interval for sensitivity and specificity were as follows: computed
      tomography 81% (72-88%) and 66% (53-77%), PET after a positive computed
      tomography 92% (87-95%) and 68% (51-81%), PET after a negative computed
      tomography 73% (50-88%) and 86% (75-93%) and PET after an indeterminate computed
      tomography 100 and 68%. The area under the summary receiver operating curve was
      0.82 for computed tomography and 0.94 for PET. There was no heterogeneity or
      publication bias. CONCLUSIONS: Our results suggest that although adding Fluro
      deoxy-glucose positron emission tomography to the diagnostic work-up may enhance
      the diagnosis of pancreatic malignancy, its usefulness will vary depending upon
      the pretest probability of the patient, the results of computed tomography and
      the provider's testing thresholds. Further evaluation using a well-designed
      prospective study with a cost-effectiveness analysis is needed to clarify the
      appropriate role of Fluro-deoxy-glucose positron emission tomography.

PMID- 15569109
TI  - Meta-analysis: the efficacy, adverse events, and adherence related to first-line
      anti-Helicobacter pylori quadruple therapies.
AB  - BACKGROUND: Owing to rising drug-resistant Helicobacter pylori infections,
      currently recommended proton-pump inhibitor-based triple therapies are losing
      their efficacy, and regimens efficacious in the presence of drug resistance are
      needed. AIMS: To summarize the efficacy, safety and adherence of first-line
      quadruple H. pylori therapies in adults. METHODS: Meta-regression models
      identified factors explaining variation in the efficacy of first-line quadruple
      therapies from 145 treatment arms. Estimates of average efficacy were calculated
      within homogeneous groups. RESULTS: Quadruple therapy containing a gastric acid
      inhibitor, bismuth, metronidazole and tetracycline was enhanced when omeprazole
      was included, treatment duration lasted 10-14 days, and when therapy took place
      in the Netherlands, Hong Kong and Australia. Treatment efficacy decreased as the
      prevalence of metronidazole resistance increased. Even in areas with a high
      prevalence of metronidazole resistance, this quadruple regimen eradicated more
      than 85% of H. pylori infections when it contained omeprazole and was given for
      10-14 days. Furthermore, in the presence of clarithromycin resistance, this
      quadruple regimen eradicated 90-100% of H. pylori infections, while the currently
      recommended triple therapy containing clarithromycin, amoxicillin and a proton
      pump inhibitor eradicated only 25-61% (P < 0.001). Adherence and adverse events
      for quadruple therapy were similar to currently recommended triple therapies.
      CONCLUSIONS: Guidelines should include quadruple therapy with a proton-pump
      inhibitor, a bismuth compound, metronidazole and tetracycline among recommended
      first-line anti-H. pylori therapies.

PMID- 15569110
TI  - A novel diagnostic tool for detecting oesophageal pathology: the PillCam
      oesophageal video capsule.
AB  - BACKGROUND: Gastro-oesophageal reflux disease is a common entity. Erosive
      oesophagitis, ulcers and Barrett's oesophagus, which is found in up to 10% of
      gastro-oesophageal reflux disease patients, characterize severe gastro
      oesophageal reflux disease. Patients with Barrett's oesophagus have 0.5% per
      patient-year risk of developing oesophageal adenocarcinoma. Currently, it appears
      that a minority of those at risk for Barrett's oesophagus undergo screening in
      part because of the costs associated with endoscopy as well as risks of sedation.
      A new ingestible PillCam oesophageal capsule developed may offer an alternative
      office-based approach to visualize the oesophagus without sedation. AIM: To
      compare the oesophageal capsule to conventional upper endoscopy for detection of
      oesophageal pathologies. METHODS: A newly developed capsule, which acquires video
      images from both ends of the device at a 4 frame/s rate, was ingested by 17
      fasting patients with suspected oesophageal disorders. An ingestion procedure
      aimed to lengthen capsule transit time in the oesophagus was utilized.
      Subsequently, a standard upper endoscopy was carried out. The investigator
      interpreting the capsule findings was blinded to the endoscopy results and vice
      versa. Patients with dysphagia, known Zenker's diverticulum, intestinal
      obstruction, cardiac pacemaker or pregnancy were excluded. RESULTS: Twelve of the
      17 patients examined had oesophageal findings using the endoscope as the gold
      standard. Capsule endoscopy identified oesophageal pathology in all 12 of these
      patients and an additional pathology in one patient that was missed during
      endoscopy. For the purpose of this study, this finding was regarded as a false
      positive. The mean oesophageal passage time was 189 +/- 280 s. The positive
      predictive value of the oesophageal capsule for any oesophageal pathology was 92%
      and the negative predictive value was 100%. Oesophageal capsule sensitivity was
      100% and specificity 80%. There were neither swallowing difficulties nor
      complications subsequent to ingestion in any subjects. Seventy-three percentage
      of patients preferred the oesophageal capsule procedure on conventional
      endoscopy. Only one patient preferred oesophagogastroduodenoscopy. CONCLUSIONS:
      This pilot study has shown that oesophageal capsule endoscopy is an accurate,
      convenient, safe and well-tolerated method to screen patients for significant
      oesophageal disorders. No sedation is required, which may allow simple, office
      based screening and assessment. Further, large-scale studies are necessary to
      more fully assess this novel diagnostic tool.

PMID- 15569111
TI  - Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly
      either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs.
AB  - BACKGROUND: Although administration of gastroprotective drugs may reduce the risk
      of peptic ulcers associated with the chronic use of non-steroidal anti
      inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy
      is effective for short-term prevention, particularly in old age. AIM: To evaluate
      the risk of peptic ulcer associated with acute and chronic non-steroidal anti
      inflammatory drugs or aspirin therapy in elderly subjects, and the influence of
      antisecretory treatment on this risk. METHODS: The study included 676 elderly non
      steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who
      consecutively underwent upper gastrointestinal endoscopy. The use of non
      steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs
      (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview.
      Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection
      were carried out by endoscopy and histological examination of the gastric mucosa.
      RESULTS: About 47.3% of patients were acute and 52.7% chronic users of non
      steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted
      for age, gender, H. pylori infection and antisecretory drug use was higher in
      acute (gastric ulcer: odds ratio, OR = 4.47, 95% CI: 3.19-6.26 and duodenal
      ulcer: OR = 2.39, 95% CI: 1.73-3.31) than chronic users (gastric ulcer: OR =
      2.80, 95% CI: 1.97-3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22-2.33). Proton
      pump inhibitor treatment was associated with a reduced risk of peptic ulcer in
      both acute (OR = 0.70, 95% CI: 0.24-2.04) and chronic (OR = 0.32, 95% CI: 0.15
      0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely,
      concomitant treatment with H2-blockers was associated with a significantly higher
      risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87-30.9) and chronic (OR
      = 6.26, 95% CI: 2.56-15.3) non-steroidal anti-inflammatory drugs/aspirin users
      than non-users. Proton-pump inhibitor treatment resulted in an absolute risk
      reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal
      anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to
      avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin
      users was three both in acute and chronic users. CONCLUSIONS: These findings
      suggest that proton-pump inhibitor co-treatment is advisable in symptomatic
      elderly patients who need to be treated with non-steroidal anti-inflammatory
      drugs and/or aspirin for a short period of time.

PMID- 15569112
TI  - Esomeprazole 40 mg i.v. provides faster and more effective intragastric acid
      control than pantoprazole 40 mg i.v.: results of a randomized study.
AB  - BACKGROUND: Oral esomeprazole 40 mg provides greater acid control than oral
      pantoprazole 40 mg. AIM: To compare the effects on intragastric acid control of
      esomeprazole 40 mg administered intravenously with pantoprazole 40 mg
      intravenously. METHODS: Healthy Helicobacter pylori-negative male and female
      subjects were enrolled into this single-centre, open, randomized, two-way
      crossover study. Esomeprazole 40 mg intravenously and pantoprazole 40 mg
      intravenously were administered as 15-min infusions once daily at 09:00 hours for
      5 days. Continuous 24-h intragastric pH monitoring was carried out at baseline
      and on days 1 and 5. RESULTS: pH-data were available for all 25 subjects who
      completed the study. Esomeprazole 40 mg intravenously resulted in 8.3 and 13.9 h
      with an intragastric pH > 4 on days 1 and 5 compared with 5.3 and 9.0 h,
      respectively for pantoprazole 40 mg intravenously (day 1: P < 0.001, day 5: P <
      0.0001). During the first 4 h of dosing on day 1 corresponding values were 1.7
      and 0.6 h respectively (P < 0.0001). A mean median pH above 4 on day 5 was only
      attained with esomeprazole 40 mg intravenously. CONCLUSIONS: Once-daily dosing
      with esomeprazole 40 mg intravenously provides faster and more pronounced
      intragastric acid control than pantoprazole 40 mg intravenously.

PMID- 15569113
TI  - Pantoprazole provides rapid and sustained symptomatic relief in patients treated
      for erosive oesophagitis.
AB  - BACKGROUND: Effective symptom control is a primary concern of most heartburn
      suffers. AIM: To compare the safety and efficacy of pantoprazole, placebo and the
      H2 antagonist nizatidine in relieving symptoms in patients with erosive
      oesophagitis. METHODS: Data from two randomized, double-blind studies were
      pooled. Patients received pantoprazole 10, 20 or 40 mg, or placebo daily (study
      1, n = 603), or pantoprazole 20 or 40 mg daily or 150-mg nizatidine b.d. (study
      2, n = 243) for either 4 or 8 weeks. Endoscopy was performed at baseline, week 4
      and week 8. Persistent absence of symptoms was defined as the first day that no
      symptoms were reported by the patient on that day or any subsequent study day.
      RESULTS: A significantly higher percentage (P < 0.05) of pantoprazole patients
      reported elimination of all symptoms by week 8. Daytime heartburn, night-time
      heartburn and regurgitation were significantly better controlled with
      pantoprazole (with a dose-response at most time-points). Absence of symptoms was
      a powerful predictor of healing; presence of symptoms correlated poorly.
      CONCLUSION: Pantoprazole is more effective than placebo or nizatidine for
      controlling heartburn and acid regurgitation in patients with erosive
      oesophagitis. Relief of GERD symptoms is highly predictive of healing of erosive
      oesophagitis at 4 and 8 weeks.

PMID- 15569114
TI  - Outcomes in elderly patients following surgery for colorectal cancer in the
      veterans affairs health care system.
AB  - AIM: To compare 30-day and 5-year mortality in elderly vs. younger patients
      following surgical resection for colorectal cancer. METHODS: A cohort study of
      patients admitted to VA hospitals with a new diagnosis of colorectal cancer who
      underwent surgical resection between October 1990 and September 2000. Cumulative
      survival rates (30-day and 5-year) were calculated from Kaplan-Meier estimates
      and adjusted risks of death were estimated using Cox proportional hazards models.
      RESULTS: We identified 34,888 individuals with a new diagnosis of colorectal
      cancer between October 1990 and September 2000, of whom 22 633 (65%) underwent
      surgical resection. The 30-day mortality following resection for rectal and colon
      cancer, respectively, for patients <65 years was 2.1 and 2.8% compared with 4.9
      and 5.6% for those > or =65 years. The 5-year cumulative survival for rectal and
      colon cancer for patients <65 years was 54.0 and 57.6% compared with 44.5 and
      46.6% for those > or =65 years. In patients > or =65 years with rectal or colon
      cancer, after adjustment, 30-day mortality was 2 times greater and 5-year
      mortality was 1 times greater than in younger patients. CONCLUSIONS: Older age is
      an independent predictor of increased short-term and long-term mortality
      following surgery in patients with rectal and colon cancer.

PMID- 15569115
TI  - Clinical experience of patients undergoing photodynamic therapy for Barrett's
      dysplasia or cancer.
AB  - INTRODUCTION: Barrett's oesophagus is the most important risk factor in the
      increase in incidence of oesophageal adenocarcinoma. Photodynamic therapy using
      porfimer sodium is the only approved endoscopic treatment for use in patients
      with Barrett's high-grade dysplasia. AIM: To determine clinical characteristics,
      endoscopic findings and treatment complications in Barrett's high-grade dysplasia
      patients undergoing photodynamic therapy. METHODS: We reviewed our experience
      using porfimer sodium photodynamic therapy to treat patients with Barrett's
      oesophagus and high-grade dysplasia or mucosal carcinoma. Data collected included
      patients characteristics, presentation symptoms, endoscopic findings, subsequent
      use of surveillance endoscopy and outcome after photodynamic therapy. RESULTS:
      Since 1997, 102 patients with Barrett's high-grade dysplasia (69 patients) or
      mucosal adenocarcinoma (33 patients) have been treated with photodynamic therapy
      using porfimer sodium as an alternative to oesophagectomy (median series follow
      up time = 1.6 years). Almost half (46%) of patients had high-grade dysplasia or
      carcinoma detected on their first endoscopy and the remainder (54%) were found
      during surveillance of known Barrett's oesophagus. Symptoms typically associated
      with oesophageal disease were only found in 29 of 47 (62%) patients in whom
      dysplasia/carcinoma was detected on the initial endoscopy - chest pain in 13
      patients, dysphagia in nine patients and chronic gastro-oesophageal disease in
      seven patients. Comparison of endoscopic characteristics found the median
      Barrett's glandular segment length was significantly shorter in adenocarcinoma
      patients (median 3 cm; range: 1-12) vs. Barrett's high-grade dysplasia patients
      (median 5 cm; range: 1-16, P < 0.001). Overall treatment results found complete
      ablation of glandular epithelium with one course of photodynamic therapy in most
      patients (56%). Stricture requiring dilation occurred in 20 patients (20%) was
      the most common serious adverse event. Photodynamic therapy failed to ablate
      dysplasia or carcinoma in four patients and subsequent oesophagectomy was
      curative in three of these patients. CONCLUSIONS: Approximately 40% of newly
      diagnosed patients with Barrett's associated dysplasia or carcinoma had no
      oesophageal symptoms and had carcinoma associated with short segment (3 cm or
      less). Photodynamic therapy is a highly effective, safe and minimally invasive
      first-line treatment for patients with Barrett's dysplasia and mucosal
      adenocarcinoma.

PMID- 15569116
TI  - Randomized placebo-controlled trial assessing the effect of bifidobacteria
      fermented milk on active ulcerative colitis.
AB  - BACKGROUND: Probiotics are efficacious for treating and maintaining remission of
      ulcerative colitis. AIM: To conduct a randomized placebo-controlled trial of
      bifidobacteria-fermented milk supplementation as a dietary adjunct in treating
      active ulcerative colitis. METHODS: Twenty patients with mild to moderate,
      active, ulcerative colitis randomly received 100 mL/day of bifidobacteria
      fermented milk or placebo for 12 weeks with conventional treatment. RESULTS:
      Clinical and endoscopic activity indices and histological scores were similar in
      the two groups before treatment. Although improvements were significant in both
      groups, the clinical activity index was significantly lower in the bifidobacteria
      fermented milk than in the placebo group after treatment. The post-treatment
      endoscopic activity index and histological score were significantly reduced in
      the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal
      butyrate, propionate and short-chain fatty acid concentrations were significant
      in the bifidobacteria-fermented milk, but not the placebo group. No adverse
      effects were observed in either group. CONCLUSION: Supplementation with this
      bifidobacteria-fermented milk product is safe and more effective than
      conventional treatment alone, suggesting possible beneficial effects in managing
      active ulcerative colitis. This is a pilot study and further larger studies are
      required to confirm the result these preliminary results.

PMID- 15569117
TI  - Anti-Saccharomyces cerevisiae mannan antibodies in inflammatory bowel disease:
      comparison of different assays and correlation with clinical features.
AB  - BACKGROUND: Anti-Saccharomyces cerevisiae mannan antibodies have been proposed as
      a new serological marker associated with Crohn's disease. However, their clinical
      value is still unclear; furthermore, a standardization of anti-S. cerevisiae
      mannan measurements is lacking. AIM: In this study, we aimed to assess the
      correlation between anti-S. cerevisiae mannan detection and specific clinical
      features in Crohn's disease and ulcerative colitis. Moreover, we tested the
      concordance of four different anti-S. cerevisiae mannan assays. MATERIALS AND
      METHODS: Serum samples from 196 patients with Crohn's disease, 197 patients with
      ulcerative colitis and 100 unrelated healthy controls were tested for anti-S.
      cerevisiae mannan with a standard enzyme-linked immunosorbent assay method
      (Lille) by one of the authors (VP). Subsequently, 60 randomly selected serum
      samples (27 Crohn's disease, 28 ulcerative colitis and five healthy controls)
      were tested for anti-S. cerevisiae mannan with three different commercial kits.
      RESULTS: With the Lille assay, anti-S. cerevisiae mannan were detected in 100 of
      196 patients with Crohn's disease (51%; P < 0.0001 vs. controls), 32 of 197
      patients with ulcerative colitis (16%; P < 0.02 vs. controls), and six of 100
      controls (6%). No correlation between presence of anti-S. cerevisiae mannan and
      specific clinical features was found in both ulcerative colitis and Crohn's
      disease patients. The percentages of anti-S. cerevisiae mannan detected with four
      different assays ranged from 28 (Bouty) up to 43% (Inova), but these differences
      did not reach statistical significance. The concordance rate of anti-S.
      cerevisiae mannan detection in the four assays was very low (11 concordant
      results of 60 samples, 18.3%) (k = 0.15). No improvement of the concordance rate
      was obtained by modifying the suggested cut-off values (k = 0.20). CONCLUSION: In
      this study, we confirm that anti-S. cerevisiae mannan are significantly more
      frequent in Crohn's disease patients compared with ulcerative colitis patients (P
      < 0.0001) and controls. However, no correlation with clinical features was found
      in both ulcerative colitis and Crohn's disease. The low prevalence of anti-S.
      cerevisiae mannan, at least in our population, and the low concordance rate
      between different assays, makes the clinical role of this marker questionable.

PMID- 15569118
TI  - Symptomatic gastro-oesophageal reflux, arousals and sleep quality in patients
      undergoing polysomnography for possible obstructive sleep apnoea.
AB  - INTRODUCTION: Nocturnal acid reflux is common and could disturb sleep by causing
      arousals that fragment sleep. AIM: To determine the prevalence of gastro
      oesophageal reflux symptoms and their association with arousals, stages of sleep
      and quality of life in patients undergoing evaluation for excessive daytime
      sleepiness and obstructive sleep apnoea. METHODS: Ninety-four consecutive
      patients with excessive daytime sleepiness were prospectively studied. Patients
      completed the gastrointestinal symptom rating scale, a validated symptom
      questionnaire for reflux disease and a disease-specific quality of life
      questionnaire, the sleep apnoea quality of life index and then underwent
      overnight polysomnography, which was read in a blinded manner. RESULTS: There
      were 40 males and 54 females with a mean age of 47 +/- 13 years. Reflux symptoms
      were present in 63 of the 94 (67%) patients. Patients with reflux symptoms had
      significantly more arousals from sleep 43 +/- 70/h than those without (20 +/-
      24/h; P = 0.03). The sleep duration during the second stage of sleep was shorter
      (44 +/- 21%) for those with reflux symptoms than those without (52 +/- 12%; P =
      0.03). Patients with reflux spent significantly shorter periods in stage II sleep
      (44 +/- 21%) than those without (52 +/- 12%; P = 0.03). The sleep-related quality
      of life score in patients with gastro-oesophageal reflux (3.1 +/- 1.1) was
      significantly lower than in patients without reflux (3.7 +/- 1.0; P = 0.02).
      Regression analysis demonstrated a significant inverse correlation between
      quality of life and reflux symptom score (P =0.002) and total spontaneous
      arousals (P = 0.04). CONCLUSIONS: Gastro-oesophageal reflux is common in patients
      with sleep disorders, is associated with increased arousal, decreased durations
      spent in the deeper stages of sleep and poorer sleep-related quality of life.

PMID- 15569119
TI  - Do physicians correctly assess patient symptom severity in gastro-oesophageal
      reflux disease?
AB  - BACKGROUND: The accuracy of physicians' assessment of the severity of gastro
      oesophageal reflux disease is unclear. AIM: To correlate physician and patient
      assessment of gastro-oesophageal reflux disease severity and its response to
      treatment. METHODS: Adult uninvestigated gastro-oesophageal reflux disease
      patients (n = 217) completed symptom and health-related quality of life
      questionnaires at baseline and after treatment with esomeprazole 40 mg p.o.
      daily. Pearson coefficients quantified correlations between physician assessments
      and patient responses. RESULTS: At baseline, the strongest correlations were
      heartburn severity (0.31), overall symptom severity (0.44) and a domain of the
      quality of life in reflux and dyspepsia questionnaire (0.31) (P < 0.001).
      Correlations of change with treatment were greater than baseline correlations:
      heartburn (0.39), overall symptoms (0.50) and global rate of change -- stomach
      problems (0.72, all P < 0.001). The mean difference between the physicians'
      assessment of change and the patients' global rating of change was 0.20 (95%
      confidence intervals: 0.10-0.29) with physicians overestimating benefit.
      CONCLUSIONS: Correlations were often significant, although weak to moderate and
      better with symptom severity than with health-related quality of life instruments
      as well as with change after therapy than at baseline. Increasing attention to
      health-related quality of life may help physicians better understand patients'
      experience. In clinical trials, treatment success should be assessed by the
      patient as well as the physician.

PMID- 15569120
TI  - Classification of dyspepsia and response to treatment with proton-pump
      inhibitors.
AB  - BACKGROUND: Lacking an objective 'gold standard' for diagnosing dyspepsia,
      several symptom-based classifications have been suggested. AIM: To assess if
      response to proton-pump inhibitor treatment could provide useful information for
      current or future dyspepsia classification. METHODS: Post hoc analyses of 829
      patients treated with omeprazole or placebo in a randomized-controlled trial. The
      'true' response to omeprazole (trial response minus placebo response) was
      assessed according to different classifications of dyspepsia and different
      symptoms. RESULTS: Symptoms described with the words 'burning' or 'sour' and
      patients with reflux-like dyspepsia demonstrated high response to omeprazole
      treatment, whereas patients with abdominal pain or ulcer-like dyspepsia responded
      unpredictably to omeprazole. The response to omeprazole in patients with
      epigastic pain was related to the pattern of other dyspeptic symptoms. Patients
      with heartburn or regurgitation overlapped extensively with patients with
      epigastric pain. CONCLUSION: The study demonstrated significant problems in the
      current classification of dyspepsia: 'the most bothersome symptom' was not
      independently related to the omeprazole effect and, in patients with abdominal
      pain, the response to omeprazole was dependent on the presence or absence of
      other dyspeptic symptoms. The overlap of symptoms indicates that heartburn and
      regurgitation should be recognized as symptoms of dyspepsia in primary care.

PMID- 15569121
TI  - Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori
      treatment: randomized, double-blind, placebo controlled trial.
AB  - BACKGROUND: Helicobacter pylori eradication fails in about 10% of patients,
      particularly because of the occurrence of resistance to antibiotics and side
      effects. During anti-H. pylori therapy, probiotics have been successfully used to
      reduce the incidence of side-effects. AIM: To evaluate the effect of Bacillus
      clausii, a probiotic, on incidence (primary variable) and severity of antibiotic
      associated side-effects during anti-H. pylori therapy. METHODS: One hundred and
      twenty H. pylori-positive patients were randomly screened to receive: (i) a
      standard 7 days triple therapy with rabeprazole 20 mg b.d., clarithromycin 500 mg
      b.d. and amoxicillin 1 g b.d. and B. clausii t.d.s. (each preparation containing
      2 x 10(9) spores) for 14 days starting from the first day of treatment. (ii) The
      same 7 days triple therapy and placebo t.d.s. for 14 days starting from the first
      day of treatment. Side-effects were assessed using a validated questionnaire and
      were recorded for 4 weeks from the start of therapy. RESULTS: The incidences of
      nausea, diarrhoea and epigastric pain in patients treated with B. clausii were
      significantly lower than in placebo group, in both PP and ITT analysis. Equally,
      intensity of nausea and diarrhoea in patients treated with B. clausii was
      significantly lower than in placebo group. There were no differences in adherence
      to treatment and H. pylori eradication rates between groups. Conclusion : In
      symptom-free, H. pylori-positive subjects B. clausii bacteriotherapy reduces the
      incidence of the most common side-effects related to anti-H. pylori antibiotic
      therapy compared with placebo.

PMID- 15569122
TI  - High-dose vitamin E supplementation does not diminish ribavirin-associated
      haemolysis in hepatitis C treatment with combination standard alpha-interferon
      and ribavirin.
AB  - BACKGROUND: Ribavirin is associated with haemolytic anaemia. Antioxidants have
      been reported to decrease severity of this anaemia. AIM: To determine effect of
      vitamin E supplementation on ribavirin-associated haemolysis in chronic hepatitis
      C treated with standard alpha-interferon and ribavirin. METHODS: Fifty-one naive
      chronic hepatitis C patients were randomized to receive either alpha
      interferon/ribavirin therapy (control) or therapy plus vitamin E 800 IU b.d. with
      24-week follow-up. Alanine aminotransferase ALT, haemoglobin and reticulocyte
      percentage were monitored. Symptoms and health-related quality of life were also
      monitored at each visit. RESULTS: Forty-seven subjects were treated (27 vitamin E
      /20 controls). Thirteen withdrew because of adverse effects or non-compliance.
      Groups were similar in demographics, genotype and baseline lab indices.
      Comparison with baseline, treatment and follow-up values showed a significant
      haemoglobin and ALT reduction in both groups. There was no significant difference
      in haemoglobin and reticulocyte percentage between groups. Sustained viral
      response was not significantly different between vitamin E (11/18) and control
      (6/16) groups. Three patients required ribavirin dose-reduction in the vitamin E
      group compared with two controls. Health-related quality of life during and end
      of-treatment was not different between groups. CONCLUSIONS: Vitamin E
      supplementation alone during standard alpha-interferon and ribavirin therapy does
      not appear to diminish ribavirin-associated haemolysis.

PMID- 15569123
TI  - Comorbidity of irritable bowel syndrome in general practice: a striking feature
      with clinical implications.
AB  - BACKGROUND: Somatic comorbid symptoms might identify irritable bowel syndrome
      patients with different aetiologies and needs of treatment. AIMS: To measure
      comorbid symptoms in patients with irritable bowel syndrome in general practice,
      and to explore characteristics of patients with low, intermediate and high
      somatic comorbidity. METHODS: Prospective study of 208 of 278 consecutive
      patients with irritable bowel syndrome (Rome II) in nine general practices.
      Questionnaires assessed 22 comorbid symptoms (subjective health complaint
      inventory), psychosocial factors including psychological distress (Symptom Check
      list-10) and quality of life (Short form-12). Subjective health complaint data
      from 1240 adults (controls) constituted a reference material. Patients with low,
      intermediate and high somatic comorbidity were identified by a somatic
      comorbidity score (17 subjective health complaint items). Health care seeking was
      assessed after 6-9 months. RESULTS: Patients with irritable bowel syndrome (67%
      females, mean age 50, s.d. 16) reported 20 of 22 comorbid symptoms significantly
      more frequent than controls (odds ratios = 2-7, P < 0.001). The somatic
      comorbidity score correlated with psychological distress (R = 0.46, P < 0.001).
      Patients with high somatic comorbidity reported higher levels of mood disorder,
      health anxiety, neuroticism, adverse life events and reduced quality of life and
      increased health care seeking when compared to those with low and intermediate
      somatic comorbidity (P-values < 0.05). CONCLUSIONS: Our findings support the
      hypothesis that structured assessment of comorbid somatic symptoms might identify
      subgroups with different aetiology and needs of treatment.

PMID- 15569124
TI  - Agreements among traditional Chinese medicine practitioners in the diagnosis and
      treatment of irritable bowel syndrome.
AB  - BACKGROUND: Traditional Chinese Medicine was frequently used by patients with
      irritable bowel syndrome. AIM: To evaluate the agreement on diagnoses and
      prescription of irritable bowel syndrome among Traditional Chinese Medicine
      practitioners. METHODS: Consecutive irritable bowel syndrome patients were
      interviewed independently by four Traditional Chinese Medicine practitioners. The
      study was divided into three phases: (i) blinded individual assessment, (ii)
      discussion to achieve consensus on diagnosis and treatment, (iii) individual
      assessment based on consensual diagnostic criteria. Patients with other causes of
      diarrhoea were recruited as controls in phase (iii). Percentage agreement and
      kappa-value in diagnosis, treatment principle and regime were determined.
      RESULTS: Thirty-nine irritable bowel syndrome patients were assessed in phase (i)
      whereas 65 irritable bowel syndrome patients and 17 non-irritable bowel syndrome
      controls were studied in phase (iii). The mean agreement rates in diagnosis,
      treatment principle and regimen were: 57, 58 and 52% for phase (i) and 80, 81 and
      80% for phase (iii) (P = 0.002). Accordingly, there was significant improvement
      in the mean kappa-values in diagnosis (0.11-0.34, P = 0.015) and treatment
      principle (0.16-0.37, P = 0.002) but not in treatment regime. CONCLUSIONS:
      Variations in diagnosis and treatment principles do exist among Traditional
      Chinese Medicine practitioners. Concordant diagnosis can be reached by mutual
      understanding and converging opinion among Traditional Chinese Medicine
      practitioners.

PMID- 15569126
TI  - Persistent poor glycaemic control in adult Type 1 diabetes. A closer look at the
      problem.
AB  - Around 25% of the adult Type 1 diabetes population is in persistent poor
      glycaemic control and thus at increased risk of developing microvascular
      complications. We here discuss correlates of long-standing poor glycaemic control
      and review the efficacy of clinical strategies designed to overcome persistent
      poor control. Only a few studies have identified determinants and correlates of
      long-standing poor glycaemic control in Type 1 diabetes. There is some evidence
      implicating genetic factors, as well as lower economic status, and psychological
      factors, including lack of motivation, emotional distress, depression and eating
      disorders. Ways of improving glycaemic control include strategies to enable self
      management, e.g. motivational strategies, coping-orientated education,
      psychosocial therapies, and/or intensifying insulin injection therapy plus
      continuous subcutaneous insulin infusion. Long-standing poor glycaemic control
      appears to be a heterogeneous and complex phenomenon, for which there is no
      simple, single solution. Comprehensive psycho-medical assessment in diabetes care
      may prove useful in tailoring interventions. Further research is warranted, to
      increase our understanding how psychosocial and biomedical factors, separately
      and in interaction, determine poor outcomes in Type 1 diabetes.

PMID- 15569127
TI  - Intravenous drug abuse and Type 1 diabetes: financial and healthcare
      implications.
AB  - AIMS: To determine the morbidity, mortality and healthcare costs of intravenous
      drug-abusing patients with Type 1 diabetes (IVDA-DM), who are admitted to
      hospital. METHODS: Retrospective case note analysis of admissions, complications
      and cost estimation over a 6-year period. Each drug-abusing patient (IVDA-DM) (n
      = 9) was compared with two controls (n = 18) with Type 1 diabetes but without a
      history of intravenous drug abuse (DM-controls). Admissions were also analysed
      for patients with intravenous drug abuse, but without Type 1 diabetes (IVDA
      controls) (n = 198). Admissions were at a University teaching hospital in
      Liverpool, UK. DM-controls were drawn from a population attending diabetes
      outpatient clinics between 1997 and 2002 at the same hospital. The main outcome
      measures were: the duration and healthcare costs of hospital admissions per year,
      outpatient attendances per year, glycated haemoglobin (HbA(1c)), weight, micro-
      and macrovascular complications and mortality. RESULTS: Multiple admissions,
      mainly related to ketoacidosis, led to marked differences in mean (95% CI)
      inpatient days per year per patient [IVDA-DM 28.1 (13.6-42.7) vs. DM-control 1.1
      (0.2-1.9); P < 0.0001], mean inpatient days per year per patient in critical care
      bed (IVDA-DM 1.7 (-0.7-4.2) vs. DM-control 0; P < 0.02) and mean costs of
      admission, per patient per year (pound sterling 7320 vs. pound sterling 230). The
      IVDA-DM group frequently omitted insulin, were underweight, failed to attend as
      outpatients and five had died by the end of 2002. The IVDA-controls spent
      considerably less time in hospital [3.4 (2.8-3.9) days per patient per year].
      CONCLUSION: IVDA-DM patients have higher rates of diabetes complications, are
      admitted more frequently and have a high mortality compared with DM and IVDA
      controls. The cost of inpatient care of this small group of patients was
      considerable.

PMID- 15569128
TI  - Effects of a structured health education programme by a diabetic education nurse
      on cardiovascular risk factors in Chinese Type 2 diabetic patients: a 1-year
      prospective randomized study.
AB  - AIMS: To assess the effect of regular diabetic health education on cardiovascular
      risk factors in Chinese Type 2 diabetic patients. METHODS: This was a 1-year
      prospective randomized study. One hundred and eighty Type 2 diabetic subjects
      were recruited from three regional diabetic centres in Hong Kong. Ninety received
      additional structured reinforcement of diabetic health education by a trained
      nurse after the doctors' consultations every 3 months (intervention group). The
      others received the same medical care except no nursing reinforcement (control
      group). Outcome measures included fasting plasma glucose, HbA(1c), body mass
      index, waist circumference, blood pressure and lipid profiles, which were
      assessed before the study and after 1 year. RESULTS: Two of the controls
      defaulted follow-up. The intervention group and controls had similar age and sex
      distribution. At the end of study, the intervention group had reducted their
      waist circumference, diastolic blood pressure, HbA(1c), total cholesterol and low
      density lipoprotein cholesterol levels. The controls had reduced their total
      cholesterol and low-density lipoprotein cholesterol levels. Other cardiovascular
      risk factors were not significantly changed in the controls. Addition of drugs
      and/or dosage increment of anti-diabetic drugs, lipid-lowering agents and anti
      hypertensive agents were similar between the two groups. CONCLUSIONS: Regular
      structured reinforcement with diabetic health education is useful. It helps to
      control more successfully some of the cardiovascular risk factors in Chinese Type
      2 diabetic patients.

PMID- 15569129
TI  - Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type
      2 diabetes treated with rosiglitazone.
AB  - AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators
      have recently been identified as regulators of cellular proliferation,
      inflammatory responses and lipid and glucose metabolism. These agents prevent
      coronary arteriosclerosis and improve left ventricular remodelling and function
      in heart failure after myocardial infarction. Improvement in myocardial metabolic
      state may be one of the mechanisms behind these findings. The aim of this study
      was to investigate the effects of rosiglitazone on myocardial glucose uptake in
      patients with Type 2 diabetes. Placebo and metformin were used as control
      treatments. METHODS: Forty-four patients were randomized to treatment with
      rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week
      double-blinded trial. Myocardial glucose uptake was measured using [(18)F]-2
      fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET)
      during euglycaemic hyperinsulinaemia before and after the treatment. RESULTS:
      Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from
      38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole
      body glucose uptake by 36% (P = 0.01), while metformin treatment had no
      significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole
      body glucose uptake. Myocardial work as determined by the rate-pressure-product
      was similar between the groups. Neither treatment had any significant effect on
      fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia
      were more suppressed in the rosiglitazone group (-47%, P = 0.02). Myocardial
      glucose uptake correlated inversely to FFA concentrations both before (r =-0.54,
      P = 0.002) and after (r = -0.43, P = 0.01) the treatment period in the pooled
      data. Furthermore, the increase in myocardial glucose uptake correlated inversely
      with interleukin-6 (IL-6) concentrations (r = -0.58, P = 0.03). CONCLUSIONS: In
      addition to the improvement in whole body insulin sensitivity, rosiglitazone
      treatment enhances insulin stimulated myocardial glucose uptake in patients with
      Type 2 diabetes, most probably due to its suppression of the serum FFAs.

PMID- 15569130
TI  - Feasibility of a quality assurance programme of bedside blood glucose testing in
      a hospital setting: 7 years' experience.
AB  - AIMS: Description of the long-term use of a quality assurance (QA) programme for
      bedside capillary blood glucose (CBG) testing in a general hospital. METHODS: The
      main points of the programme were selection of instrumentation using a
      standardized testing procedure, design and implementation of a quality control
      (QC) procedure, and training and motivation of nurses. The QC procedures
      consisted of a daily aqueous control and a weekly split-sample control (a
      measurement on a capillary blood sample using the glucose meter and on a
      simultaneously drawn venous sample with the laboratory analyser). When the result
      was out of range, a laboratory technician visited the ward to investigate the
      problem. All wards received a weekly report. RESULTS: The programme was
      introduced in 1995 and followed up through 2002. The split-sample control was
      more efficient in detecting clinically relevant errors than the aqueous control.
      Most errors (91-97%) were operator-related rather than instrument-related. The
      compliance with the split-sample controls remained high, with 84-91% of weekly
      controls performed over 7 years. Respectively 91, 95 and 96% of the measurements
      remained within the range of +/- 20% of the laboratory value in the years 2000,
      2001 and 2002. CONCLUSION: A QA programme of bedside CBG testing can successfully
      be implemented. It is feasible to obtain a satisfying level of measurement
      accuracy and to maintain a high level of compliance with the programme over
      several years. Split-sample controls are an essential part of the control
      procedure.

PMID- 15569131
TI  - Aqueous levels of macrophage migration inhibitory factor and monocyte chemotactic
      protein-1 in patients with diabetic retinopathy.
AB  - AIMS: To investigate the relationship of aqueous macrophage migration inhibitory
      factor (MIF) and monocyte chemotactic protein-1 (MCP-1) levels with the clinical
      stage of diabetic retinopathy. METHODS: We assayed MIF and MCP-1 levels in
      aqueous humour samples obtained from 40 diabetic patients (49 eyes) and 24 non
      diabetic patients (31 eyes) using enzyme-linked immunosorbent assay. According to
      the clinical stage of diabetic retinopathy, the diabetic patients were classified
      into non-diabetic retinopathy (11 eyes), non-proliferative diabetic retinopathy
      (14 eyes) and proliferative diabetic retinopathy (24 eyes). RESULTS: The aqueous
      levels of MIF (mean +/- sd) were 6.34 +/- 4.53 ng/ml in proliferative diabetic
      retinopathy, 3.22 +/- 1.71 ng/ml in non proliferative diabetic retinopathy, 1.25
      +/- 0.96 ng/ml in non-diabetic retinopathy and 1.07 +/- 0.94 ng/ml in non
      diabetic patients. Significant differences were found among these four groups (P
      < 0.0001). Aqueous MCP-1 levels were 1668.6 +/- 1442.3 pg/ml in proliferative
      diabetic retinopathy, 1528.6 +/- 1994.6 pg/ml in non-proliferative diabetic
      retinopathy, 690.2 +/- 402.1 pg/ml in non-diabetic retinopathy and 622.7 +/-
      245.3 pg/ml in non-diabetic patients. Significant differences were also found
      among these four groups (P < 0.0001). After correcting for total aqueous protein,
      the ratios of MIF and MCP-1 to total protein remained significantly correlated
      with the clinical stage of diabetic retinopathy (P < 0.0001, P = 0.0004,
      respectively). The ratios of MIF to total protein significantly correlated with
      the ratios of MCP-1 to total protein in diabetic patients (r = 0.680, P <
      0.0001). CONCLUSIONS: Aqueous MIF levels significantly correlated with aqueous
      MCP-1 levels and the clinical stage of diabetic retinopathy. The results suggest
      that MIF has a co-operative role with MCP-1 in the progression of diabetic
      retinopathy.

PMID- 15569132
TI  - Effect of insulin treatment on the body composition of Type 2 diabetic patients.
AB  - OBJECTIVE: Insulin is used commonly in Type 2 diabetes and is often accompanied
      by weight gain. The composition of this weight gain is poorly understood.
      Predominant increases in fat mass could increase cardiovascular risks. The aim of
      the study was to evaluate insulin-induced body composition changes. RESEARCH
      DESIGN AND METHODS: Body weight and composition of 35 Type 2 diabetic patients
      during their first 6 months of insulin therapy was compared with those in 34 Type
      2 diabetic individuals treated with insulin for at least 1 year prior to
      commencing the study. Body composition was determined by the simultaneous
      measurement of body water spaces and body density. RESULTS: Over 6 months,
      glycaemic control improved in the new treatment group only (HbA(1c): 7.26 +/-
      0.81 vs. 9.66 +/- 1.60%; P < 0.0001), remaining stable in the previously treated
      group (7.67 +/- 1.25 vs. 7.76 +/- 1.26%; P = NS). Weight significantly increased
      over time in the newly treated group (+1.7 kg; P = 0.04), but not in the
      previously treated group (-0.3 kg). It comprised of both fat (+0.85 kg) and fat
      free mass (+0.55 kg). Total body water remained unchanged. Using bioelectrical
      impedance analysis, the gain in fat mass was +2.2 kg; P = 0.048. CONCLUSIONS:
      Over 6 months, insulin therapy leads to a weight gain of 1.7 kg because of an
      increase in both fat and fat-free mass. When body composition is determined by
      bioelectrical impedance analysis, the results are biased by fluctuations in
      hydration.

PMID- 15569133
TI  - Early parasympathetic neuropathy associated with elevated fasting plasma C
      peptide concentrations and late parasympathetic neuropathy with hyperglycaemia
      and other microvascular complications.
AB  - AIMS: To examine the relationship between parasympathetic neuropathy,
      hyperinsulinaemia, glycaemic control (HbA(1c)), and future diabetic
      complications. METHODS: We assessed parasympathetic nerve function
      [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic
      control (HbA(1c)), fasting plasma (f-p-) C-peptide in 82 Type 2 diabetic patients
      (age 61 +/- 1 years) 5 and 12-15 years after diagnosis. Diabetic retinopathy was
      assessed 15 years after diagnosis. RESULTS: High HbA(1c) values in the first
      study were associated with retinopathy (with 8.6 +/- 2.0 vs. without retinopathy
      6.2 +/- 1.9%; P < 0.0001) and disturbed parasympathetic nerve function (low E/I
      ratio; r(s) = -0.41; P = 0.0061) in the second study, as well as with
      deteriorations in GFR between the first and second study (r(s) = 0.62; P <
      0.0001). Patients with parasympathetic neuropathy in the first study had
      significantly higher f-p-C-peptide concentrations than those without 3 years
      (1.20 +/- 0.43 vs. 0.86 +/- 0.40 nmol/l; P = 0.0015) and 5 years (1.20 +/- 0.44
      vs. 0.82 +/- 0.33 nmol/l; P < 0.0001), but not 15 years after diagnosis.
      CONCLUSION: High HbA(1c) values 5 years after diagnosis of Type 2 diabetes were
      associated with retinopathy, disturbed parasympathetic nerve function, and
      deterioration in GFR 7-10 years later. Parasympathetic neuropathy 5 years after
      diagnosis was associated with high C-peptide concentrations. Parasympathetic
      nerve function has to be considered when beta-cell function is evaluated.
      Hyperglycaemia is an important factor for the development of complications in
      Type 2 diabetes.

PMID- 15569134
TI  - Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha
      gene and the relationship to beta-cell function during an OGTT in glucose
      tolerant women with and without previous gestational diabetes mellitus.
AB  - AIMS: In pregnancies complicated by gestational diabetes mellitus (GDM) an
      increased demand for insulin is not met due to beta-cell dysfunction. An Ala/Val
      polymorphism at codon 98 of the hepatocyte nuclear factor-1alpha (HNF-1alpha)
      gene has been associated with decreased serum insulin and C-peptide responses
      during an oral glucose tolerance test (OGTT) in glucose-tolerant subjects. The
      aims of the present study were to evaluate the influence of the polymorphism on
      the serum insulin and C-peptide responses to an OGTT in glucose-tolerant women
      with and without previous GDM and to investigate if this polymorphism is
      associated with GDM. METHODS: The Ala/Val98 polymorphism was measured in 376
      women of Danish origin with previous GDM, and in 724 age-matched and 310 middle
      aged glucose tolerant women using polymerase chain reaction-restriction fragment
      length polymorphism. RESULTS: The allelic frequency of the Ala/Val98 polymorphism
      was 0.043 [95% confidence interval (CI) 0.028, 0.057] in women with previous GDM
      vs. 0.037 (95% CI 0.028, 0.047) in age-matched and 0.039 (95% CI 0.024, 0.054) in
      middle-age women. Among 117 glucose-tolerant women with previous GDM, 10 carriers
      of the Ala/Val98 polymorphism had a non-significant 27% and 22% reduction in
      serum C-peptide and insulin levels, respectively, at 30 min during an OGTT.
      Seventy-eight control subjects carrying the Ala/Val98 polymorphism had a 10% (P =
      0.001) and 16% (P = 0.004) reduction in serum C-peptide and insulin levels,
      respectively, compared with 956 Ala/Ala control subjects. CONCLUSIONS: The
      Ala/Val polymorphism at codon98 of HNF-1alpha is not associated with GDM in
      Danish women. However, the codon 98 variant is associated with a significant
      impairment of serum insulin and C-peptide responses during an OGTT in glucose
      tolerant women without previous GDM.

PMID- 15569135
TI  - Exploring the idiotypes of insulin antibodies as markers for remission in Type 1
      diabetes.
AB  - AIMS: Complete or partial remission can occur in newly diagnosed Type 1 diabetes
      patients. We created idiotype-specific reagents to explore the idiotypes of
      insulin antibodies (IA) in a patient in remission, and to compare with a patient
      who was not. METHODS: Phage display was used to create a library of phagotopes
      specific to insulin binding in four sera. Sera from a Type 1 diabetes subject
      deemed to have undergone remission were taken at diagnosis and again during
      remission. Sera from a non-remitter were taken at diagnosis and after 3 months on
      insulin. Phagotopes from the four sera were randomly selected and tested for
      insulin specificity in a radiobinding assay by using sera from remitters and non
      remitters. RESULTS: IA-binding phagotope selected from serum during remission
      displaced insulin binding in all nine IA(+) remitters and all 10 IA(+) non
      remitters. IA-binding phagotope selected from the non-remission patient (3 months
      after insulin therapy) displaced insulin binding in 8/9 IA(+) remitters and 8/10
      IA(+) non-remitters. The consensus peptide sequences adduced from the phages were
      identical for both these phagotopes. Phagotopes derived from insulin autoantibody
      positive individuals at diagnosis were unable to displace insulin binding in the
      IA(+) sera 3 months later, whether in remission or not. CONCLUSIONS: We have
      established the principle of using phage display in the investigation of insulin
      antibodies during remission in Type 1 diabetes. The immunological characteristics
      of IA 3 months after the introduction of insulin treatment were different from
      those at diagnosis of Type 1 diabetes (IAA). Using phage display technology, it
      was not possible to distinguish insulin antibodies according to remission status.

PMID- 15569136
TI  - Aldose reductase gene polymorphisms and susceptibility to microvascular
      complications in Type 2 diabetes.
AB  - AIMS: The gene encoding the human aldose reductase, the first and rate-limiting
      enzyme of the polyol pathway of glucose metabolism, is a promising candidate gene
      which may contribute to diabetic microvascular complications. We investigated the
      association of two previously reported DNA sequence variants of this gene, the C
      106T polymorphism and the (CA)(n) dinucleotide repeat marker, with the risk of
      albuminuria and retinopathy in Finnish Type 2 diabetic patients and non-diabetic
      control subjects. METHODS: The study population included 85 Finnish, middle-aged,
      newly diagnosed Type 2 diabetic patients and 126 non-diabetic control subjects.
      Genetic analyses were performed using the polymerase chain reaction, restriction
      fragment length polymorphism, and automated laser fluorescence scanning analyses.
      Microvascular complications were determined using 10-year follow-up data of
      urinary albumin excretion measurements and ophthalmological examinations.
      RESULTS: The C and Z-2 alleles of the C-106T polymorphism and the (CA)(n) repeat
      marker, respectively, were found to be more frequent in Type 2 diabetic subjects
      than in non-diabetic subjects. The C and Z-2 alleles were in 60% linkage
      disequilibrium in diabetic subjects. At the time of diagnosis, diabetic subjects
      with the T allele of the C-106T polymorphism had significantly higher urinary
      albumin excretion rate and prevalence of albuminuria than subjects with the C
      106C genotype (prevalence of albuminuria: 33.3 vs. 13.8%, P = 0.036, odds ratio =
      3.9, 95% confidence interval 1.1, 14.7). The Z-2 allele of the (CA)(n) repeat
      marker was not consistently associated with the prevalence of albuminuria. No
      associations were observed between the polymorphisms examined and the prevalence
      of retinopathy at any point of the follow-up. CONCLUSIONS: The present study
      suggests that the C-106T polymorphism of the aldose reductase gene could be
      involved in the early development of microalbuminuria in Finnish Type 2 diabetic
      patients.

PMID- 15569137
TI  - Erythromelia, or Mitchell's syndrome--new names for unexplained signs of
      inflammation in distal symmetrical neuropathy in diabetes.
AB  - BACKGROUND: Two cases are described in which distal symmetrical sensorimotor
      neuropathy complicating diabetes was associated with episodes of subacute
      vasodilation of one or other lower limb, and which were otherwise unexplained.
      The vasodilation was associated with swelling and stiffness, but was painless and
      self-limiting. INTERPRETATION: It is suggested that this phenomenon results from
      disordered vasoregulation in diabetic neuropathy, and is linked to the processes
      which underlie diabetic neuropathic osteoarthropathy (Charcot foot), as well as
      disorders such as complex regional pain syndrome-1 (CRPS-1, reflex sympathetic
      dystrophy) and erythromelalgia. CONCLUSIONS: As self-limiting vasodilation may be
      not uncommon in distal symmetrical neuropathies, but unrecognized because the
      phenomenon has not been named, the terms 'neuropathic erythromelia' or
      'Mitchell's syndrome' are proposed. The adoption of either of these names may
      lead to earlier diagnosis and prevent inappropriate investigation and treatment.

PMID- 15569138
TI  - Association of simple anthropometric measures of obesity with visceral fat and
      the metabolic syndrome in male Caucasian and Indo-Asian subjects.
AB  - AIMS: The aims of this study were first, to investigate the relationship between
      simple anthropometric measures of obesity with visceral fat as assessed by a
      single slice magnetic resonance imaging (MRI)-scan in patients attending a
      hospital clinic. Second, to determine which anthropometric measure best relates
      to the adverse metabolic profile of the metabolic syndrome. METHODS: Forty-one
      male subjects [body mass index (BMI): 30.2 + 5.8 kg/m(2), age: 50.3 + 13.6 years]
      were studied by MRI-scan to measure visceral fat at L4/L5 level and to
      investigate its relationship with simple anthropometric measures. Second, we
      studied 83 male subjects to determine which anthropometric measure best predicts
      the metabolic complications (using the ATPIII criteria) of obesity in the setting
      of a hospital clinic. RESULTS: Waist circumference was the best anthropometric
      measurement that correlated with MRI-visceral fat mass assessed at L4/L5 in 41
      subjects who had an MRI scan (P = 0.0001, r(2) = 0.36, beta = 0.56) amongst
      variables which also included age, BMI, sagittal diameter, diabetes and
      ethnicity. Stepwise multiple regression analysis showed sagittal diameter (P =
      0.001, r(2) = 0.4, beta = 0.406), age (P = 0.003, beta = 0.271) and waist
      circumference (P = 0.012, beta = 0.297) were the best predictors of the adverse
      metabolic profile of the metabolic syndrome in all 83 male subjects amongst BMI,
      waist-hip ratio (WHR), ethnicity and diabetes-related factors. CONCLUSIONS: Waist
      circumference is a simple anthropometric parameter that best correlates with
      single slice MRI-scan, but sagittal diameter (measured using abdominal calipers)
      better predicts the adverse metabolic profile of the metabolic syndrome. Although
      there is considerable variation in abdominal fat topography between ethnic
      groups, and also within populations, sagittal diameter assessment is a technique
      that is simple and best predicts the metabolic syndrome.

PMID- 15569139
TI  - Oxidative stress and glucose levels in a population-based sample.
AB  - OBJECTIVES: To examine the relationship between markers of oxidative status and
      glucose on a population basis. STUDY DESIGN AND SETTING: We report here on a
      population-based sample of 1315 women and 981 men, aged 35-79 years, randomly
      selected from residents of Erie and Niagara Counties in western New York between
      1996 and 1999. Thiobarbituric reactive substances (TBARS), erythrocyte
      glutathione (GSH) and plasma glutathione peroxidase (GSH-Px) were measured as
      markers of oxidative status. Study sample was categorized by quartiles of
      glucose, degree of abnormality of fasting glucose, and level of metabolic control
      in patients with diabetes. RESULTS: Men and women in the uppermost quartiles of
      glucose had higher levels of TBARS (men: Quartile 4 = 1.55 +/- 0.03, Quartile 1 =
      1.36 +/- 0.03, women: 1.49 +/- 0.02, 1.30 +/- 0.02 nmol/ml) and lower levels of
      GSH (men: Quartile 4 = 1.57 +/- 0.03, Quartile 1 = 1.69 +/- 0.03, women: 1.71 +/-
      0.03, 1.97 +/- 0.0 mmol/l packed RBCs). In women, compared with normal fasting
      glucose, impaired fasting glucose was associated with higher levels of TBARS
      (1.29 +/- 0.01 vs. 1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.85 +/- 0.02 vs.
      1.76 +/- 0.05 mmol/l packed RBCs), and higher GSH-Px activity (618.94 +/- 2.64
      vs. 644.77 +/- 8.90 IU/l). In women, abnormal fasting glucose was associated with
      higher levels of TBARS (1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.68 +/-
      0.06 mmol/l packed RBCs), and higher levels of GSH-Px (647.72 +/- 9.87 IU/l) than
      normal or impaired fasting glucose. In men, abnormal fasting glucose was
      associated with higher TBARS (1.76 +/- 0.04 vs. 1.37 +/- 0.07 nmol/ml), and lower
      GSH (1.62 +/- 0.05 vs. 2.78 +/- 0.02 mmol/l packed RBCs), than normal fasting
      glucose. Poor metabolic control was associated with higher TBARS (men: 2.07 +/-
      0.08 vs. 1.33 +/- 0.14 nmol/l, women: 2.02 +/- 0.09 vs. 1.35 +/- 0.18 nmol/l) and
      GSH-Px activity (men: 654.34 +/- 13.45 vs. 599.86 +/- 24.76, women: 660.61 +/-
      13.25 vs. 579.42 +/- 27.42 IU/l). CONCLUSIONS: Glucose levels play a role in
      determining oxidative status in a population sample. The balance between
      oxidative and antioxidant processes appears to be sensitive to glucose levels
      with moderate elevations of glucose affecting the oxidative status.

PMID- 15569140
TI  - Prevalence of diabetic eye disease in Tayside, Scotland (P-DETS) study:
      methodology.
AB  - AIMS: To describe the use of a validated diabetes register for sampling frame
      generation and assessment of the representative nature of participants in a
      fieldwork study of diabetic eye disease. METHODS: We performed an observational,
      cross-sectional fieldwork study of diabetic retinal disease using reference
      standard eye examination. We sampled the entire diabetic population using the
      Diabetes Audit and Research in Tayside Study (DARTS) diabetes register. RESULTS:
      The study population comprised 4825 diabetic patients aged over 16 years
      registered with one of 166 general practitioners (GPs) in 41 practices in Tayside
      in October 1999. This represented 61.1% of the Tayside diabetic population
      (7903). A total of 586 (66%; 95% confidence interval 63, 70) patients were
      examined from a sampling frame of 882 living patients registered with a Tayside
      GP. Demographic and disease parameters recorded on the DARTS patient register
      allowed comparison between participants and non-participants. CONCLUSIONS: This
      study shows the clear benefit of using a complete diabetic population as a
      sampling frame. This allows potential selection bias and external validity to be
      evaluated using routine data sources. Studies performed and reported in this way
      will aid the critical appraisal process.

PMID- 15569141
TI  - Evaluation of delivery of enhanced diabetes care to patients of South Asian
      ethnicity: the United Kingdom Asian Diabetes Study (UKADS).
AB  - AIMS: We tested the hypothesis that enhanced care for diabetes, tailored to the
      needs of the South Asian community with Type 2 diabetes, would improve risk
      factors for diabetic vascular complications and ultimately reduce morbidity and
      mortality. PATIENTS AND METHODS: The study was a cluster randomized controlled
      trial (RCT) with general practice the unit of randomization. Six West Midlands
      general practices with a high proportion of South Asian patients were randomized
      to 'enhanced care' using Asian link workers and extra community diabetes
      specialist nurse sessions (intervention) or continued standard practice care
      (control). RESULTS: Of 401 patients recruited to the study, 361 (90%), comprising
      178 from Coventry and 183 from Birmingham were eligible and included in the
      analyses. The mean age at baseline (standard deviation, SD) was 58.9 (11.7 years)
      with median (interquartile range; IQR) duration of diabetes 6.5 (3-11) years. At
      one year follow-up there was a significant difference in reduction of systolic
      (4.6 mmHg, P = 0.035) and diastolic blood pressure (3.4 mmHg, P = 0.003) and
      total cholesterol (0.4 mmol/l, P = 0.005), comparing the intervention and control
      groups. After adjusting for baseline measurement and age, only differential
      reduction in diastolic blood pressure remained significant. There was no
      significant change in HbA(1c) and no difference between the groups. CONCLUSIONS:
      Using link workers and extra community diabetes specialist nurse input together
      with treatment protocols in primary care might prove a useful strategy in working
      towards NSF targets for diabetes management. In this study, small reductions in
      blood pressure and cholesterol were achieved. Improvement in glycaemic control
      may require longer and possibly different strategies. Further research is
      required to evaluate fully the effectiveness, including the costs and longer term
      sustainability of culturally sensitive initiatives.

PMID- 15569142
TI  - Reversible cognitive deterioration after a single episode of severe
      hypoglycaemia: a case report.
AB  - A case of a male 34-year-old Type 1 diabetic patient who experienced a prolonged
      severe hypoglycaemic episode is presented. After the hypoglycaemic event, the
      patient suffered from moderate to severe neuropsychological impairments. On the
      basis of neuropsychological assessment results, diabetes therapy was modified
      (less complex insulin regimen, fixed insulin doses and fixed carbohydrate
      distribution). At a follow-up examination (3 months), presumable complete
      recovery of cognitive function was observed. This case demonstrates the possible
      detrimental neuropsychological effects of severe hypoglycaemia, that, in this
      case, turned out to be reversible. It highlights the clinical implications of
      impaired cognitive function on self-care and self-management abilities and the
      usefulness of neuropsychological testing in clinical diabetes care.

PMID- 15569143
TI  - Changing aspirin use in patients with Type 2 diabetes in the UKPDS.
AB  - AIMS: To examine the proportion of UK Prospective Diabetes Study (UKPDS) patients
      with Type 2 diabetes taking aspirin regularly for the primary and secondary
      prevention of cardiovascular disease (CVD) before and after publication of the
      1997 American Diabetes Association (ADA) Clinical Practice Recommendations and
      the 1998 Joint British Recommendations on the Prevention of Coronary Disease in
      Clinical Practice. METHODS: UKPDS annual review data from 1996/7 (n = 3190) and
      2000/1 (n = 2467) were used to determine the prevalence of patients taking
      aspirin regularly in relation to known CVD risk factors and pre-existing CVD.
      RESULTS: Patients taking aspirin regularly were more often male than female (24
      vs. 20%, P = 0.0033), older (66 +/- 8 vs. 62 +/- 9 years, P < 0.0001) and less
      often Afro-Caribbean than White Caucasian or Indian Asian (11 vs. 23 vs. 22%,
      respectively, P < 0.0001). Between 1996/7 and 2000/1 aspirin use in patients
      without pre-existing CVD increased from 17 to 31% (P < 0.0001) and for those with
      pre-existing CVD from 76 to 82% (P = 0.032). CONCLUSION: The majority of patients
      with pre-existing CVD were taking aspirin regularly. Although aspirin use in
      those without pre-existing CVD approximately doubled after publication of the ADA
      and Joint British Recommendations, less than two-thirds of these high-risk
      patients were being treated according to guidelines. This may relate to a lack of
      convincing evidence for primary CVD prevention or failure to adhere to
      guidelines. It may be that more trial data is needed to convince clinicians of
      the value of aspirin therapy in Type 2 diabetes.

PMID- 15569145
TI  - The cost-effectiveness of continuous subcutaneous insulin infusion compared with
      multiple daily injections for the management of diabetes: response to Scuffham
      [corrected] and Carr.

PMID- 15569146
TI  - Re: post-prandial hypoglycaemia due to insulin lispro or insulin aspart.

PMID- 15569147
TI  - DNA binding properties of human DNA polymerase eta: implications for fidelity and
      polymerase switching of translesion synthesis.
AB  - The human XPV (xeroderma pigmentosum variant) gene is responsible for the cancer
      prone xeroderma pigmentosum syndrome and encodes DNA polymerase eta (pol eta),
      which catalyses efficient translesion synthesis past cis-syn cyclobutane thymine
      dimers (TT dimers) and other lesions. The fidelity of DNA synthesis by pol eta on
      undamaged templates is extremely low, suggesting that pol eta activity must be
      restricted to damaged sites on DNA. Little is known, however, about how the
      activity of pol eta is targeted and restricted to damaged DNA. Here we show that
      pol eta binds template/primer DNAs regardless of the presence of TT dimers.
      Rather, enhanced binding to template/primer DNAs containing TT dimers is only
      observed when the 3'-end of the primer is an adenosine residue situated opposite
      the lesion. When two nucleotides have been incorporated into the primer beyond
      the TT dimer position, the pol eta-template/primer DNA complex is destabilized,
      allowing DNA synthesis by DNA polymerases alpha or delta to resume. Our study
      provides mechanistic explanations for polymerase switching at TT dimer sites.

PMID- 15569148
TI  - Novel heat shock protein HspQ stimulates the degradation of mutant DnaA protein
      in Escherichia coli.
AB  - Escherichia coli DnaA protein initiates chromosomal replication and is an
      important regulatory target during the replication cycle. In this study, a
      suppressor mutation isolated by transposon mutagenesis was found to allow growth
      of the temperature-sensitive dnaA508 and dnaA167 mutants at 40 degrees C. The
      suppressor consists of a transposon insertion in a previously annotated ORF, here
      termed hspQ, a novel heat shock gene whose promoter is recognized by the major
      heat shock sigma factor sigma32. Expression of hspQ on a pBR322 derivative
      inhibits growth of the dnaA508 and dnaA167 mutants at 30 degrees C, whereas
      growth of dnaA46 and other dnaA mutants is insensitive to changes in the level of
      hspQ. Cellular DnaA508 protein is degraded rapidly at elevated temperature, but
      hspQ disruption impedes this process. In contrast, DnaA46 protein is rapidly
      degraded in an hspQ-independent manner. Gel-filtration and chemical cross-linking
      experiments suggest that HspQ forms a stable homodimer in solution and can form
      homomultimers consisting of about four monomers. Heat-shock induced proteases
      such as Clp contain homomultimers of subunit proteins. We propose that HspQ is a
      new factor involved in the quality control of proteins and that it functions by
      excluding denatured proteins.

PMID- 15569149
TI  - High-throughput screening of genome fragments bound to differentially acetylated
      histones.
AB  - Although acetylation-deacetylation of histones contributes to regulation of gene
      expression, few methods have been available to determine the whole-genome histone
      acetylation profile in specific cells or tissues. We have now developed a genome
      wide screening method, differential chromatin scanning (DCS), to isolate genome
      fragments embedded in histones subject to differential acetylation. This DCS
      screening was applied to a human gastric cancer cell line incubated with or
      without an inhibitor of histone deacetylase (HDAC) activity, resulting in the
      rapid identification of more than 250 genome fragments. Interestingly, a number
      of cancer-related genes were revealed to be the targets of HDAC in the cancer
      cells, including those for tumour protein 73 and cell division cycle 34. Such
      differential acetylation of histone was also shown to be linked to the regulation
      of transcriptional activity of the corresponding genes. Among the isolated genome
      fragments, 94% (32/34) of them were confirmed to be bound to differentially
      acetylated histones, and the genes corresponding to 78% (7/9) of them exhibited
      differential transcriptional activity consistent with the level of histone
      acetylation. With its high fidelity, the DCS method should open a possibility to
      rapidly compare the genome-wide histone acetylation profiles and to provide novel
      insights into molecular carcinogenesis.

PMID- 15569150
TI  - In vitro transcription analysis by reconstituted cyanobacterial RNA polymerase:
      roles of group 1 and 2 sigma factors and a core subunit, RpoC2.
AB  - The RNA polymerase (RNAP) core enzyme of cyanobacterium Synechocystis sp. strain
      PCC 6803 was reconstituted with overproduced recombinant subunits and purified
      with C-terminal histidine-tagged RpoA. The core enzyme with purified a sigma
      factor, SigA/SigD or SigB, allowed specific in vitro transcription from the light
      inducible psbA2 or the dark-/heat-inducible lrtA/hspA promoters, respectively.
      Further analysis using a mutant psbA2 promoter revealed that the -35 hexamer of
      the promoter was essential for SigA but not SigD. Similar but distinct patterns
      of psbA2 transcription were found for two types of RNAP, cyanobacterial
      (alpha2betabeta'gamma) and E. coli (alpha2betabeta') core enzymes. Specific
      binding of PCC 6803 RpoC2 (beta') to E. coli core enzyme and its contribution to
      efficient psbA2 transcription by RNAP-SigA/D suggest that this subunit could
      confer an important role on the cyanobactrial RNAP. Differences in affinity and
      specificity among cyanobacterial sigma factors for the core enzyme and promoters
      were discussed.

PMID- 15569151
TI  - Hub1 is an essential ubiquitin-like protein without functioning as a typical
      modifier in fission yeast.
AB  - Hub1 exhibits 23% sequence identity to ubiquitin. However, Hub1 lacks the C
      terminal Gly, which is essential for covalent attachment to target protein(s) of
      ubiquitin and other ubiquitin-like (UBL) modifiers. Instead, Hub1 proteins in all
      eukaryotes retain the di-Tyr just before a single variable residue at the C
      terminus, so one intriguing question is whether Hub1 could be linked to substrate
      through the conserved Tyr or not. Here we studied Hub1 in Schizosaccharomyces
      pombe. Gene disruption experiment revealed that hub1+ is essential. Remarkably,
      the mutant cells harbouring Hub1 lacking the di-Tyr could grow similar to wild
      type cells, indicating that the di-Tyr is dispensable for the essential function
      of Hub1. Moreover, we could not observe cleavage of Flag-tag fused with C
      terminus of Hub1. It suggests that the processing for conjugation via conserved
      Tyr is not likely to occur in Hub1, and Hub1 is a novel class of the UBL protein
      family. Finally, we isolated a temperature-sensitive allele, hub1-1. This
      temperature sensitivity could be suppressed by overproduction of Rpb10 or Snu66,
      the former of which is one of the common subunits of the RNA polymerases and the
      other is the component of the spliceosome. We also observed that pre-mRNA
      splicing was impaired in hub1-1.

PMID- 15569152
TI  - The AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 genes, which encode functionally
      redundant kinesins, are essential for cytokinesis in Arabidopsis.
AB  - Cytokinesis is the critical step during which daughter cells are separated. We
      showed previously that a protein complex that consists of NACK1 (and NACK2)
      kinesin-like protein and NPK1 MAPKKK and its substrate NQK1 MAPKK are required
      for progression of cytokinesis in Nicotiana tabacum. The genome of Arabidopsis
      thaliana encodes homologues of NACK1 and NACK2, namely, AtNACK1/HINKEL and
      STUD/TETRASPORE/AtNACK2, respectively. Loss-of-function mutations in
      AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 result in the occasional failure of
      somatic and male-meiotic cytokinesis, respectively. However, it is likely that
      these genes function redundantly to some extent in somatic tissues and female
      gametogenesis. We describe the phenotypes of Arabidopsis plants that have
      mutations in both the AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 genes. These
      phenotypes suggest that the two genes are essential during both male and female
      gametogenesis. Female gametes with atnack1 atnack2 double mutations failed to
      cellularize and to generate a central cell, synergids and the egg cells. Male
      gametes with atnack1 atnack2 mutations were also not transmitted to the next
      generation. The AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 genes for kinesin-like
      proteins have overlapping functions that are essential for gametogenetic
      cytokinesis. They appear to be essential components of a MAP kinase cascade that
      promotes cytokinesis of plant cells in both gametophytic (haploid) and
      sporophytic (diploid) proliferation.

PMID- 15569153
TI  - Differentiation status dependent function of FOG-1.
AB  - The molecular interactions between transcription factors and cofactors play
      crucial roles in various biological processes, including haematopoiesis. FOG-1 is
      a cognate cofactor of GATA-1, and the FOG-1/GATA-1 complex is essential for the
      haematopoietic differentiation of erythroid cells and megakaryocytes. In order to
      elucidate the biological functions of FOG-1 in the different contexts of cell
      differentiation, we analysed the effects of FOG-1 expression on haematopoietic
      cell differentiation, using a combination of in vitro differentiation of mouse
      embryonic stem (ES) cells and conditional gene expression. FOG-1 suppressed the
      proliferation of primitive and definitive erythroid cells in all stages of
      differentiation. However, FOG-1 inhibited and enhanced megakaryopoiesis in the
      early and late differentiation stages, respectively, through different molecular
      mechanisms. In addition, FOG-1 inhibited the proliferation of ES cells, the
      molecular mechanism of which differs from those of erythroid and megakaryocytic
      cells. These results suggest that FOG-1 functions in a cell differentiation
      context-dependent manner.

PMID- 15569154
TI  - Modulation of GDF5/BRI-b signalling through interaction with the tyrosine kinase
      receptor Ror2.
AB  - The brachydactylies are a group of inherited disorders of the hands characterized
      by shortened digits. Mutations in the tyrosine kinase receptor Ror2 cause
      brachydactyly type B (BDB). Mutations in GDF5, a member of the BMP/TGF-beta
      ligand family, cause brachydactyly type C (BDC) whereas mutations in the receptor
      for GDF5, BRI-b, cause brachydactyly type A2 (BDA2). There is considerable degree
      of phenotypic overlap between the subtypes BDB, BDC and BDA2. Here we demonstrate
      that all three components are involved in GDF5 induced regulation of
      chondrogenesis. We show that Ror2 (tyrosine kinase receptor) and BRI-b
      (serine/threonine kinase receptor) form a ligand independent heteromeric complex.
      The frizzled-like-CRD domain of Ror2 is required for this complex. Within that
      complex Ror2 gets transphosphorylated by BRI-b. We show that Ror2 modulates GDF5
      signalling by inhibition of Smad1/5 signalling and by activating a Smad
      independent pathway. Both pathways however, are needed for chondrogenic
      differentiation as demonstrated in ATDC5 cells. The functional interaction of
      Ror2 with GDF5 and BRI-b was genetically confirmed by the presence of epistatic
      effects in crosses of Ror2, BRI-b and Gdf5 deficient mice. These results indicate
      for the first time a direct interaction of Ser/Thr- and Tyr-Kinase receptors and
      provide evidence for modulation of the Smad-pathway and GDF5 triggered
      chondrogenesis.

PMID- 15569155
TI  - SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH
      responsive steroidogenic cells.
AB  - Bone marrow stem cells develop into haematopoietic and mesenchymal lineages, but
      have not been known to participate in steroidogenic cell production.
      Steroidogenic factor 1 (SF-1), also designated adrenal 4 binding protein (Ad4BP),
      is an essential orphan nuclear receptor for steroidogenesis as well as for
      adrenal and gonadal gland development. In the present study, we revealed that the
      adenovirus-mediated forced expression of SF-1 can transform cultured primary long
      term cultured bone marrow cells into steroidogenic cells, showing the de novo
      synthesis of multiple steroid hormones in response to adrenocorticotropic hormone
      (ACTH). This finding may provide an initial step in innovative autograft cell
      transfer therapy for steroid hormone deficiencies.

PMID- 15569156
TI  - The adaptor molecule FADD from Xenopus laevis demonstrates evolutionary
      conservation of its pro-apoptotic activity.
AB  - FADD is an adaptor protein that transmits apoptotic signals from death receptors
      such as Fas to downstream initiator caspases in mammals. We have identified and
      characterized the Xenopus orthologue of mammalian FADD (xFADD). xFADD contains
      both a death effector domain (DED) and a death domain (DD) that are structurally
      homologous to those of mammalian FADD. We observed xFADD binding to Xenopus
      caspase-8 and caspase-10 as well as to human caspase-8 and Fas through
      interactions with their homophilic DED and DD domains. When over-expressed, xFADD
      was also able to induce apoptosis in wild-type mouse embryonic fibroblasts (MEF),
      but not in caspase-8-deficient MEF cells. In contrast, DED-deficient xFADD
      (xFADDdn) acted as a dominant-negative mutant and prevented Fas-mediated
      apoptosis in mammalian cell lines. These results indicate that xFADD transmits
      apoptotic signals from Fas to caspase-8. Furthermore, we found that transgenic
      animals expressing xFADD in the developing heart or eye under the control of
      tissue-specific promoters show abnormal phenotypes. Taken together, these results
      suggest that xFADD can substitute functionally for its mammalian homologue in
      death receptor-mediated apoptosis, and we suggest that xFADD functions as a pro
      apoptotic adaptor molecule in frogs. Thus, the structural and functional
      similarities between xFADD and mammalian FADD provide evidence that the apoptotic
      pathways are evolutionally conserved across vertebrate species.

PMID- 15569157
TI  - Transcriptional regulation of multidrug resistance-1 gene by interleukin-2 in
      lymphocytes.
AB  - P-glycoprotein, encoded by the multidrug resistance (MDR)-1 gene, expels various
      drugs from cells resulting in drug resistance. However, its functional relevance
      to lymphocytes and the regulatory mechanism remain unclear. Although MDR-1 is
      known to be induced by various cytotoxic stimuli, it is poorly understood whether
      the activation stimuli such as cytokines induce MDR-1 transcription. We
      investigated the transcriptional regulation of MDR-1 in lymphocytes by activation
      stimuli, particularly by interleukin (IL)-2. IL-2 induced translocation of YB-1,
      a specific transcriptional factor for MDR-1, from the cytoplasm into nucleus of
      lymphocytes in a dose-dependent manner and resulted in the sequential events;
      transcription of MDR-1, expression of P-glycoprotein on the cell surface, and
      excretion of the intracellular dexamethasone added in vitro. Transfection of YB-1
      anti-sense oligonucleotides inhibited P-glycoprotein expression induced by IL-2.
      Cyclosporin A, a competitive inhibitor of P-glycoprotein, recovered intracellular
      dexamethasone levels in lymphocytes. We provide the first evidence that IL-2, a
      representative lymphocyte-activation stimulus, induces YB-1 activation followed
      by P-glycoprotein expression in lymphocytes. Our findings imply that lymphocytes
      activation by IL-2 in vivo, in the context of the pathogenesis of autoimmune
      diseases, results in P-glycoprotein-mediated multidrug resistance, and that P
      glycoprotein could be an important target for the treatment of refractory
      autoimmune diseases.

PMID- 15569158
TI  - The Sec14 family glycerophospholipid-transfer protein is required for structural
      integrity of the spindle pole body during meiosis in fission yeast.
AB  - The fission yeast spo20+ gene encodes a glycerophospholipid-transfer protein.
      spo20 mutants are unable to assemble the forespore membrane properly. Here we
      studied the structural integrity of the spindle pole body (SPB) in spo20-H6
      mutants during meiosis. Meiotic cells expressing a GFP-tagged SPB marker protein,
      Spo15-GFP, showed an excess number of SPBs, some of which were not localized to
      the spindle poles and were termed 'pseudo-SPBs'. Formation of spindles for
      meiosis I was significantly delayed in spo20-H6 cells, although the morphology of
      spindles and segregation of the sister chromatids seemed normal. The SPB of spo20
      H6 contained meiosis-specific outer plaques, though outermost layers were less
      evident. Time-lapse studies of spo20-H6 cells showed that the pseudo-SPBs
      originated from normal SPBs at the spindle poles during meiosis I. Among the SPB
      components tested, Spo15, Spo13, Sad1 and Cut12 were localized to the pseudo
      SPBs, but Sid4 was not always present. Alp4, a component of the gamma-tubulin
      complex, was also present in about 40% of the pseudo-SPBs. The forespore
      membranes initiated from both the SPBs and the pseudo-SPBs. We conclude that
      Spo20 plays a role in maintaining the structural integrity of the meiotic SPB,
      besides supplying membrane vesicles for forespore membrane assembly.

PMID- 15569159
TI  - Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that
      in humans.
AB  - Congenital hydronephrosis is one of the most common anomalies found in humans and
      may cause renal failure in childhood. Half of the cases are due to obstruction at
      the ureteropelvic junction (UPJ). Here we report that mice lacking Id2, an
      inhibitor of basic helix-loop-helix (bHLH) transcription factors, exhibit
      hydronephrosis mimicking the characteristics of human cases such as unilaterality
      and male preponderance. Hydronephrosis was found even in Id2+/- mice. The
      penetrance was 67.2% in Id2-/- males, 48.8% in Id2+/- males, 28.0% in Id2-/-
      females and 20.0% in Id2+/- females. Distortion or high insertion of the ureter
      at the UPJ was frequently observed and these morphological changes were evident
      in late embryogenesis. Histologically, the muscle layer, where Id2 is normally
      expressed, was hypertrophic and/or irregular at the UPJ. Furthermore, gene
      expression analysis suggested that BMP4 (bone morphogenetic protein 4), which is
      known to be involved in the development of hydronephrosis, appears to function as
      an upstream factor of Id2. Our results thus raise the possibility that Id2 is a
      gene responsible for the pathogenesis of hydronephrosis in man.

PMID- 15569160
TI  - Expression of the liver-specific gene Cyp7a1 reveals hepatic differentiation in
      embryoid bodies derived from mouse embryonic stem cells.
AB  - Hepatic differentiation from mouse embryonic stem (ES) cells via the formation of
      embryoid bodies (EBs) has been revealed by the expression of hepatocyte-related
      genes such as alpha-fetoprotein and albumin. It is known, however, that the
      visceral endoderm differentiates in early EBs and expresses these hepatocyte
      related genes. Thus, it remains unclear whether ES cells are capable of
      differentiating into hepatocytes derived from definitive endoderm in vitro. In
      the present study, yolk sac tissues isolated from the foetal mouse were found to
      express many hepatocyte-related genes. Among the hepatocyte-related genes
      examined, cytochrome P450 7A1 (Cyp7a1) was identified as a liver-specific gene
      that was not expressed in the yolk sac. Cyp7a1 was induced in developing EBs, and
      hepatic differentiation was preferentially observed in the developing EBs in
      attached culture as compared to those in suspension culture. Leukaemia inhibitory
      factor permitted the differentiation of visceral endoderm, but inhibited the
      expression of gastrulation-related genes and the hepatic differentiation in
      cultured EBs. ES cells expressing green fluorescent protein (GFP) under the
      control of the Cyp7a1 enhancer/promoter showed that cultured EBs contained GFP
      positive epithelial-like cells. These results demonstrate that ES cells can
      differentiate in vitro into hepatocytes derived from definitive endoderm.

PMID- 15569161
TI  - A survey of factor prophylaxis in the Canadian haemophilia A population.
AB  - High-dose factor prophylaxis, defined as the infusion of 25-40 factor (F) VIII
      International Units (IU) kg bodyweight (bw)(-1)> or = x 3 per week, started at
      age 1-2 years of life in boys with severe haemophilia A prevents the development
      of significant bleed-related arthropathy. However, programmes of prophylaxis are
      very expensive and venous access is a challenge. To ascertain patterns of
      prophylaxis in Canada during the period of a global shortage of recombinant FVIII
      concentrate a survey was conducted in 2001. The response rate was 83% and the
      survey identified 247 inhibitor-negative haemophilia A cases receiving
      prophylaxis, defined as the regular administration of FVIII at least once weekly,
      from 14 Canadian haemophilia treatment centres. The median age of the group
      identified was 13 years (range: 1-65) and 95% of cases had severe haemophilia A
      defined by a circulating factor level of <1%. The median FVIII infusion dose was
      26 (range: 16-33) IU kg(-1); infusions were administered > or = x 3 per week in
      67% of cases. High-dose factor prophylaxis was used most frequently in boys <5
      years of age (23 of 28 cases, 82%) as compared with 56% (56 of 100), 66% (40 of
      61) and 62% (36 of 58) of males ages 5-12, 13-18 and >18 years. Prophylaxis
      accounted for 50% of the annual Canadian FVIII consumption and was a major
      driving force in the 10% increase (=19.3 million FVIII IU) in the FVIII
      consumption in Canada in the 4-year period 1999-2003. Given the economic
      implications of increased use of prophylaxis prospective studies are warranted to
      better define optimal prophylaxis regimens in the haemophilia A population.

PMID- 15569162
TI  - Thawed cryoprecipitate stored for 6 h at room temperature: a potential
      alternative to factor VIII concentrate for continuous infusion.
AB  - Continuous infusion (CI) of factor VIII concentrates has been demonstrated to be
      cost-effective method in maintaining stable levels of FVIII activity in
      haemophilia A patients with major bleeding or undergoing major surgery.
      Cryoprecipitates remain the major source of FVIII in developing countries-like
      the Philippines because of limited availability and high cost of concentrates. To
      support the use of cryoprecipitate as alternative to FVIII concentrate for CI in
      centres with no factor concentrates, FVIII levels in 37 bags of random
      cryoprecipitate were measured at 0, 2, 4 and 6 h after thawing, kept at room
      temperature with bacteriological culture studies performed on the sixth hour. The
      mean FVIII content at hour 0 was 108.10 U per bag. Type ORh+ blood had lower
      FVIII content (+/-78.91 U per bag) compared with blood types ARh+ (+/-121.64 U
      per bag) and BRh+ (+/-117.04 U per bag). The units stored <6 months had higher
      FVIII content (+/-117.74 U per bag) compared with those stored for over 6- but
      <12-months (+/-66.77 U per bag). The mean rate of decline of FVIII activity at 2,
      4 and 6 h was statistically significant at 10.35% (P = 0.000), 21.49% (P = 0.000)
      and 29.41% (P = 0.000) from baseline, respectively, using the paired t-test.
      Similar finding was found across different blood types and storage duration. Only
      one of 37 bags grew Staphylococcus aureus on day 10 of incubation.

PMID- 15569163
TI  - A 6-year follow-up of dosing, coagulation factor levels and bleedings in relation
      to joint status in the prophylactic treatment of haemophilia.
AB  - The primary aim of this study was to investigate the possible relationship
      between coagulation factor level and bleeding frequency during prophylactic
      treatment of haemophilia after stratification of the patients according to joint
      scores. The secondary aim was to obtain a systematic overview of the doses of
      coagulation factors prescribed for prophylaxis at the Malmo haemophilia treatment
      centre during a 6-year period. A retrospective survey of medical records for the
      years 1997-2002 and pharmacokinetic study results from the 1990s was complemented
      by collection of blood samples for coagulation factor assay when needed.
      Information on the dosing and plasma levels of factor VIII or factor IX, joint
      scores and incidence of bleedings (joint bleeds and 'other bleeds') was compiled.
      The patients were stratified by age (0-6, 7-12, 13-18, 19-36 and >36 years) and
      joint score (0, 1-6 and >6). Individual pharmacokinetic parameters of plasma
      coagulation factor activities (FVIII:C and FIX:C) were estimated. Trough levels
      during the treatment were calculated, as well as the number of hours per week of
      treatment during which plasma FVIII:C/FIX:C fell below a 1, 2 or 3% target level.
      Fifty-one patients with haemophilia A (two moderate, 49 severe) and 13 with
      haemophilia B (all severe) were included, yielding data for 364 patient-years of
      treatment. There was a wide range of dosing schedules, the most common ones being
      three times a week or every other day for FVIII and twice a week or every third
      day for FIX. The overall relationship between FVIII:C/FIX:C levels and incidence
      of joint bleeding was very weak, even after stratification of the patients
      according to joint score. There was no relationship between coagulation factor
      level and incidence of other bleeds. In this cohort of patients on high-dose
      prophylactic treatment, dosing was based more on clinical outcome in terms of
      bleeding frequency than on the aim to maintain a 1% target level of
      FVIII:C/FIX:C. Some patients did not bleed in spite of a trough level of <1% and
      others did in spite of trough levels >3%. The practical implication of our
      findings is that dosing in prophylactic treatment of haemophilia should be
      individualized. Thus, proposed standard regimens should be implemented only after
      careful clinical consideration, with a high readiness for re-assessment and
      individual dose tailoring.

PMID- 15569164
TI  - Comparing hand-held computers and paper diaries for haemophilia home therapy: a
      randomized trial.
AB  - Treatment of severe haemophilia with factor concentrates is by self-infusion in
      the home. Adherence to record keeping on paper diaries is poor. A randomized
      controlled trial compared adherence with record keeping of paper diaries with
      hand-held computers. Forty-one individuals with severe haemophilia, were
      randomized to hand-held computers (n = 22) or paper diaries (n = 19) and followed
      for 6 months. About 86.2% (679 of 788) of infusions by patients in the computer
      group were in compliance with the data submission schedule compared with only
      48.3% (358 of 741) of infusions by patients using paper diaries (P < 0.0001). The
      time intervals between infusions and the receipt of data were shorter in the
      computer group (median 0.25 vs. 25 days respectively, P < 0.0001). Reminder phone
      calls by the clinic were made less frequently to users of hand-held computers
      than to users of paper diaries (median one vs. five times, P < 0.0001). Accuracy
      of data was similar for both methods. Compliance with hand-held computers was
      superior to paper diaries. The clinic received data from hand-held computers
      mostly on the same day, and nurses could thereby provide clinical advice more
      effectively. Although hand-held computers did not result in increased accuracy,
      errors could be detected and corrected more rapidly. Electronic data can more
      easily be verified, analysed and summarized than that from paper diaries.

PMID- 15569165
TI  - Management of haemophilic patients with inhibitors in major orthopaedic surgery
      by immunadsorption, substitution of factor VIII and recombinant factor VIIa
      (NovoSeven): a single centre experience.
AB  - Inhibitors of factor VIII or FIX in haemophilic patients are a common and serious
      complication associated with an increased risk of life-threatening bleeding
      during elective surgery. Substitution therapy fails to be effective, therefore an
      alternative treatment is needed. We have performed six major elective orthopaedic
      interventions in four patients with haemophilia A and inhibitors. A preoperative
      immunadsorbant therapy with Therasorb to eliminate inhibitors was successful in
      four cases, but during FVIII substitution inhibitors increased on day 4 to day 6
      after surgery, leading to decreasing FVIII levels. Therefore, therapy was changed
      to recombinant FVIIa (rFVIIa; NovoSeven). Two interventions had to be covered
      with sole rFVIIa therapy as immunadsorbant therapy failed to be effective in one
      case and the need for acute intervention did not allow pretreatment in the other.
      We did not see increased bleeding during or after surgery when compared to our
      experience with non-inhibitor haemophilic patients. In conclusion, a preoperative
      decrease of inhibitors from immunadsorbant therapy, perioperative substitution of
      FVIII and changing treatment to rFVIIa when inhibitors are increased, is a safe
      and economic therapy for guaranteeing haemostasis in major elective orthopaedic
      surgery. On the contrary, sole therapy with rFVIIa allows immediate surgical
      intervention without a long hospital stay prior to surgery and a need for
      laboratory monitoring of inhibitor titres and FVIII levels. Our findings support
      data previously published.

PMID- 15569166
TI  - Acquired factor VIII inhibitors in non-haemophilic patients: clinical experience
      of 15 cases.
AB  - We retrospectively analysed 15 non-haemophilic patients with acquired factor VIII
      inhibitors seen in our regional haemophilia centre. The median age was 55 years
      (range: 21-80). About 70% of patients older than 50 were male, while all five
      patients younger than 50 were female. The most common underlying condition was
      pregnancy or postpartum status (20%). About 27% of cases had no identifiable
      underlying condition. About 27% of patients had medical conditions that were
      unlikely to be related to acquired inhibitors. The most frequent presenting
      symptom was spontaneous haemorrhage of soft tissues, skin or joints. Twelve of 13
      (92.3%) evaluable patients achieved complete remission (CR) with prednisone alone
      and/or combined prednisone and cyclophosphamide, but their clinical courses were
      highly variable. The median time to response was 21.5 weeks (range: 2-176) and
      the median treatment duration was 9 months (range: 1.25-66). All six patients
      treated with prednisone initially, and then combined prednisone/cyclophosphamide
      if no response (NR) to prednisone within 3-4 months (three patients), achieved
      CR; while four of five patients treated initially with combined
      prednisone/cyclophosphamide had CR. Patients older than 50 years had a similar
      response rate, median time to response and median treatment duration as did
      patients younger than 50 years (83% vs. 100%; 21.5 vs. 32 weeks, and 8 vs 16.5
      months, respectively). Furthermore, the differences in the median time to
      response and treatment duration for patients with high or low baseline or peak
      inhibitor titres were negligible. Only one patient died of a treatment-related
      pulmonary aspergillosis 18 months after an acquired inhibitor was diagnosed. None
      of these patients died of bleeding complications. In conclusion, our patients
      with acquired FVIII inhibitor had highly variable clinical courses and responses
      to steroid or immunosuppressive therapy. The inhibitors in the majority of
      patients resolved in less than 6 months although in two cases it persisted for
      longer than 1 year before resolving. Treatment with prednisone alone as first
      line, then combined prednisone with cyclophosphamide if NR to prednisone seemed
      equally effective when compared with using combined prednisone and
      cyclophosphamide initially. Further studies of newer therapeutic agents such as 2
      chlorodeoxyadenosine (2-CDA) and rituximab are warranted for patients refractory
      to conventional immunosupressive therapy.

PMID- 15569167
TI  - Hepatitis C infection in children with haemophilia: a pilot study.
AB  - Many haemophilia patients were infected with hepatitis C virus (HCV) in childhood
      after transfusion with inadequately or non-virus inactivated clotting factor
      products. Limited information is available on the clinical course of HCV
      infection in children. To assess the clinical consequences of hepatitis C in
      these young patients we performed a pilot study of 31 patients with haemophilia,
      infected with HCV before the age of 13. Current median age was 20 years. Nineteen
      (61%) patients had chronic hepatitis C, whereas the remaining 12 patients
      spontaneously cleared HCV. The median duration of infection was 17 years. Among
      patients chronically infected with HCV, an enlarged liver and/or spleen on
      ultrasound was present in 59%, whereas 63% had abnormal aminotransferases and/or
      gamma-GT values. In conclusion, 39% of the patients infected in childhood cleared
      HCV spontaneously. The majority of the patients with chronic hepatitis C had
      ultrasound and/or laboratory abnormalities and these findings may be associated
      with the presence of chronic liver disease.

PMID- 15569168
TI  - Same day outpatient transjugular liver biopsies in haemophilia.
AB  - Patients with haemophilia are at increased risk of hepatitis C infection because
      of prior transfusion of blood products. Virtually all haemophiliacs who received
      pooled blood products before the mid-1980s have been infected with hepatitis C. A
      liver biopsy is important to identify the extent of liver disease, and to help
      determine the necessity of interferon therapy. With factor replacement, in
      hospital liver biopsy is safe. Thirty patients with haemophilia were evaluated
      for chronic hepatitis C infection. Eleven patients subsequently underwent
      successful transjugular liver biopsy in the outpatient setting after appropriate
      factor replacement. Mean +/- SD pre- and posthaemoglobin values were 15.8 +/-
      0.79 and 14.4 +/- 0.71 g dL(-1) (P = ns). There was no significant change in
      heart rate, systolic or diastolic blood pressure during the monitoring period (P
      = ns) and no major complication was noted in perioperative follow-up. The mean
      length of the liver biopsy specimens was 1.7 +/- 0.3 cm, mean grade was 2 +/- 0.6
      and mean stage was 2.3 +/- 1.2. Our experience demonstrates that outpatient
      transjugular liver biopsy can be safely performed in patients with haemophilia in
      the outpatient setting, avoiding the cost and need for hospital admission.

PMID- 15569169
TI  - Transfusion-transmitted virus is not present in factor IX concentrates commonly
      used to treat haemophilia B.
AB  - Transfusion-transmitted virus (TTV) is a potential cause of post-transfusion
      hepatitis in patients with haemophilia. Plasma-derived clotting factor
      concentrates currently undergo processes that are effective in removal and
      inactivation of viruses such as HIV, hepatitis B and C; however, their
      effectiveness with respect to TTV is unknown. To determine if TTV DNA is present
      in plasma-derived concentrates of factor IX, we tested 14 lots of Mononine and
      compared the results with BeneFix. Nucleic acid isolation, followed by a two
      round polymerase chain reaction (PCR) and agarose gel analysis indicated that all
      17 lots were negative for TTV. Although TTV may be considered an emerging
      pathogen, no evidence of the virus was detected in the commercially available
      plasma-derived concentrate of FIX most commonly used to treat haemophilia B.

PMID- 15569170
TI  - Successful liver transplantation in a patient with severe haemophilia A and a
      high-titre factor VIII inhibitor.
AB  - We present the case of a 61-year-old man with severe haemophilia A and a high
      titre factor VIII inhibitor who underwent successful orthotopic liver
      transplantation (OLT) for hepatocellular carcinoma. Postoperatively, a modest
      early anamnestic response to FVIII was followed by immunological tolerance to
      FVIII. This case illustrates the technical feasibility of OLT in some patients
      with high-titre inhibitors to FVIII, and suggests that immune tolerance may be
      induced by endogenously produced FVIII from the transplanted organ.

PMID- 15569171
TI  - 'MYNI's orthosis': a self-adjustable, dynamic knee extension orthosis for
      quadriceps weakness in haemophilia rehabilitation.
AB  - In developing countries like India, where walking is the primary, preferred and
      feasible mode of transport, the implications following quadriceps weakness poses
      a serious threat to ones functional independence. This has been a challenge for
      professionals while ambulating individuals with haemophilia, where quadriceps
      weakness is very common. Although external splinting has been understood for many
      years, as a means of support in haemophilia, there is still a dearth of knowledge
      in making an appropriate splint to assist or to take over the weak quadriceps
      during ambulation. This newly designed 'MYNI's orthosis' helps in versatile ways
      in addition to assisting the weak quadriceps. It provides prolonged stretch to
      contracted tissue, allows for being used as a serial cast in improving the knee
      range and is cosmetically acceptable. Above all, it is user-friendly, thus
      enhancing compliance and superior outcome in haemophilic knee rehabilitation.

PMID- 15569172
TI  - Anticoagulation in haemophilia patients with prosthetic valve replacement.

PMID- 15569173
TI  - Identification of mutations in exon 14 including five novelties in 13 Italian
      patients with haemophilia A.

PMID- 15569174
TI  - Meta-analytic evidence of increased breakthrough bleeding during prophylaxis with
      B-domain deleted factor VIII.
AB  - A recent meta-analysis of 13 observational studies suggested reduced haemostatic
      efficacy during prophylaxis and shortened half-life of B-domain deleted factor
      VIII (BDD-rFVIII) as compared with full-length factor VIII (FL-FVIII). The meta
      analysis included a multivariate model that took both dose and age into account.
      In addition, several assumptions and interpretations were required in order to
      conduct the meta-analysis. It is important to test the impact of such assumptions
      and interpretations through sensitivity analysis. In the published meta-analysis,
      results of several sensitivity analyses were described involving the effect of
      study design; heterogeneity of subjects in some studies; type of assay used for
      half-life determinations; and year of publication. In two subsequent brief
      reports, additional sensitivity analyses addressed choice of median-to-mean
      conversion factor over a wide range of scenarios and use of age at start of
      prophylaxis vs mean age during prophylaxis in the multivariate model. A
      recognized inherent difficulty in the meta-analysis of multiple published reports
      from similar studies is the possibility of some subject or data overlap.
      Therefore, the present communication details further sensitivity analyses
      encompassing assumptions regarding the possibility of subject duplication in a
      subgroup of subjects from one study and possible duplication of pharmacokinetic
      data from two smaller studies within the reports of two larger studies. All the
      sensitivity analyses support the main conclusions of the meta-analysis, namely,
      that BDD-rFVIII substantially increases the risk of breakthrough bleeding during
      prophylaxis, possibly at least partly because of shorter half-life than that of
      FL-FVIII.

PMID- 15569175
TI  - Mutation analysis in F9 gene of 17 families with haemophilia B from Iran.
AB  - Seventeen haemophilia B families from Iran were investigated to determine the
      causative mutation. All the essential regions of the F9 gene were initially
      screened by conformational sensitive gel electrophoresis and exons with band
      shift were sequenced. Seven of the 15 mutations identified in these families were
      novel mutations. The mutations were authenticated in nine families as other
      affected members or heterozygous female carriers were available for verification.

PMID- 15569176
TI  - Annual Congress of the British Society for Immunology, 7-10 Dec 2004, Harrowgate,
      United Kingdom. Abstracts.

PMID- 15569200
TI  - Surgical treatment planning in newly diagnosed breast cancer patients at high
      risk for BRCA-1 or BRCA-2 mutation.

PMID- 15569201
TI  - Initial experience with surgical treatment planning in the newly diagnosed breast
      cancer patient at high risk for BRCA-1 or BRCA-2 mutation.
AB  - Despite an abundance of information available for dealing with patients with BRCA
      1 and BRCA-2 mutations, little guidance is available to assist the surgeon in
      dealing with the genetically high-risk patient recently diagnosed with breast
      cancer. A retrospective review was undertaken of 170 patients who underwent
      genetic counseling and testing over a 3-year period from March 2000 to March
      2003. Forty-three of the 170 patients tested were diagnosed with breast cancer
      prior to genetic testing. Nine patients (20.9%) tested positive for a deleterious
      mutation. Fifty-eight percent underwent genetic counseling prior to definitive
      cancer surgery. Five of the 25 patients who underwent lumpectomy tested positive
      for a deleterious mutation. Testing results became available during systemic
      therapy or radiation was delayed until results were known. After counseling, all
      five patients testing positive went on to bilateral prophylactic mastectomy and
      reconstruction. None had radiation therapy. Because of a strong family history,
      eight patients elected to undergo prophylactic mastectomy and reconstruction
      prior to obtaining genetic test results; and despite compelling histories, all
      eight tested negative for a mutation. Treatment algorithms are developed to
      manage patients that are first discovered to be at high risk for a BRCA-1 or BRCA
      2 mutation at the time they are diagnosed with breast cancer. Patients diagnosed
      with breast cancer who are discovered to be at high risk for a genetic mutation
      should undergo counseling prior to definitive surgery. This maximizes the time
      that patients have to consider options for prophylaxis and monitoring should
      their test be positive. It also prevents women who would otherwise be candidates
      for breast preservation from undergoing unnecessary radiation therapy should they
      chose prophylactic mastectomy in the face of a positive test.

PMID- 15569202
TI  - Use of alternative therapy in postmenopausal breast cancer patients treated with
      tamoxifen after surgery.
AB  - The goal of this study was to determine the frequency of alternative therapy use
      in postmenopausal women with early stage breast cancer who were enrolled in a
      randomized clinical trial designed to determine the value of breast irradiation
      after treatment with breast-conserving surgery and tamoxifen. A questionnaire was
      given to 300 patients, ages 52 to 90 years, after completion of radiation therapy
      (if any). Of the 290 respondents, 78 (27%) had used some form of alternative
      therapy. Of these, 60.3% started after the diagnosis of breast cancer. Users of
      alternative therapies were significantly younger than nonusers (67.0 +/- 8.4
      years versus 70.0 +/- 8.7 years, p = 0.009) and they used a median of one type of
      therapy per person (range 1-13). Users of alternative therapies were more likely
      to have experienced symptoms (stiffness, pain, numbness, or swelling) in the
      ipsilateral shoulder or arm after treatment of their breast cancers compared to
      nonusers (odds ratio [OR] = 2.0, p = 0.02). This relationship between alternative
      therapy use and symptoms was strongest in the group who started alternative
      therapies after breast cancer diagnosis (OR = 2.1, p = 0.05). On multivariate
      analysis, younger age and radiotherapy treatment were related to alternative
      therapy use. In conclusion, 27% of patients with early stage breast cancer used
      alternative therapy. Users were more likely to be younger and to experience
      shoulder or arm symptoms after breast-conserving surgery with radiation.

PMID- 15569203
TI  - The negative predicative value of breast fine-needle aspiration biopsy: the
      Massachusetts General Hospital experience.
AB  - Breast fine-needle aspiration biopsy (FNAB) has been increasingly accepted as an
      important triage tool for the evaluation of breast lumps. We examined the
      clinical utility and diagnostic accuracy of a negative breast FNAB result by
      studying 450 breast aspirates in 413 patients (average age 45 years) with a
      "negative" or benign cytologic interpretation performed at Massachusetts General
      Hospital over a 4-year period. Of these patients, 121 (29%) underwent subsequent
      biopsy and 17 (4%) were found to have malignancy (3% of total negative FNABs; 14%
      with histology). None of these 17 patients had a triple negative test. A cohort
      of 115 patients had documentation of negative physical, radiologic, and cytologic
      examinations (the triple negative), none of whom were found to have malignancy on
      histologic or at least 2-year clinical follow-up (negative predictive value [NPV]
      = 100% with a triple-negative test). Outside of the triple-negative test, the NPV
      of a negative breast FNAB is reduced with a false-negative rate of 7%. However,
      in the setting of a triple-negative test, the NPV in our patient population was
      100%, reassuring the patient and clinician that clinical follow-up and not
      surgical intervention was sufficient for proper patient care.

PMID- 15569204
TI  - The safety of lymphatic mapping in pregnant breast cancer patients using Tc-99m
      sulfur colloid.
AB  - This investigation was undertaken to assess the risk to the embryo/fetus
      associated with sentinel lymph node biopsy and lymphoscintigraphy of the breast
      performed in pregnant patients. Approximately 92.5 MBq (2.5 mCi) of filtered Tc
      99m sulfur colloid was injected peritumorally the day before surgery in two
      nonpregnant women with breast cancer. The whole-body distribution of the
      radiopharmaceutical was evaluated using a gamma camera 1 hour after injection. We
      then calculated the absorbed dose to the embryo/fetus for three theoretical
      extreme scenarios of biodistribution and pharmacokinetics: 1) all of the injected
      radiopharmaceutical remains in the breast and is eliminated only by physical
      decay; 2) all of the injected radiopharmaceutical is instantaneously transported
      to the urinary bladder, where it remains and is eliminated only by physical
      decay; and 3) the injected radiopharmaceutical behaves as though it were
      administered intravenously, that is, it has the biodistribution and
      pharmacokinetics of Tc-99m sulfur colloid injected for a liver/spleen or bone
      marrow scan. The fetal radiation absorbed dose was then estimated for two Tc-99m
      dosages: 18.5 MBq (0.5 mCi) and 92.5 MBq (2.5 mCi). The Medical Internal
      Radiation Dosimetry (MIRD) program was used to estimate the absorbed doses to the
      embryo/fetus for the first two scenarios. Published data were used to calculate
      the doses for the third scenario. A single breast is not among the source organs
      in the MIRD program, so the heart was used as a surrogate in the first scenario.
      In the two breast cancer patients, whole-body gamma-camera images obtained 1 hour
      after radiopharmaceutical injection revealed no radioactivity except in the
      vicinity of the injection site. In the theoretical scenarios, with 92.5 MBq, the
      highest absorbed doses to the embryo/fetus were as follows: scenario 1, 7.74 x
      10(-2) mGy at 9 months of pregnancy; scenario 2, 4.26 mGy during early pregnancy;
      and scenario 3, 0.342 mGy at 9 months of pregnancy. The maximum absorbed dose to
      the fetus of 4.3 mGy calculated for the worst-case scenario is well below the 50
      mGy that is believed to be the threshold absorbed dose for adverse effects. Thus
      breast lymphoscintigraphy during pregnancy appears to present a very low risk to
      the embryo/fetus.

PMID- 15569205
TI  - Dual-frequency ultrasound examination of skin and subcutis thickness in breast
      cancer-related lymphedema.
AB  - Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm that
      sometimes follows breast cancer treatment. Clinically, both skin and subcutis are
      swollen. Edema is considered to be predominantly subcutaneous and of an even
      distribution. The purpose of this study was to quantify the degree and uniformity
      of skin and subcutis swelling around the forearms of women with BCRL. Ten women
      with BCRL were recruited. Both forearms were examined using 20 MHz ultrasound to
      visualize the skin and 7 MHz ultrasound to visualize the subcutis. Skin thickness
      was between the bottom of the entry-echo and the skin-subcutis boundary. Subcutis
      thickness was measured between the skin-subcutis boundary and the subcutis-muscle
      boundary. Both average skin thickness (1.97 +/- 1.00 mm) and average subcutis
      thickness (10.32 +/- 5.63 mm) were greater in the ipsilateral arm than in the
      contralateral arm (skin 1.12 +/- 0.14 mm, subcutis 5.58 +/- 2.04 mm, p < 0.01, t
      test). The degree of increase in skin thickness did not vary around the arm (p >
      0.05, ANOVA), while the degree of increase in subcutis thickness did vary (p <
      0.05). Skin thickness correlated negatively with subcutis thickness in the
      contralateral arm, but correlated positively in the ipsilateral arm. The skin and
      subcutis are thickened in the ipsilateral arm of patients with BCRL. Skin
      thickness is increased uniformly around the arm and correlates strongly with the
      degree of swelling, while subcutis swelling varies. The measurement of skin
      thickness using ultrasound may form a useful clinical tool in the diagnosis of
      lymphedema and also aid further investigation of therapeutic techniques.

PMID- 15569206
TI  - Membranous fat necrosis of the breast: diagnosis by minimally invasive technique.
AB  - Clinical and mammographic features of membranous fat necrosis (MFN) may simulate
      breast malignancy and tissue sampling is essential for accurate diagnosis. The
      aim of our study was to evaluate the clinical and imaging findings in these
      patients. Retrospective review of the records of breast biopsies (n = 1200)
      during the 5-year period 1998 to 2002 revealed eight (0.67%) cases of
      histologically proven MFN. Seven of the eight patients had a history of breast
      trauma or surgery. Seven patients underwent mammography: normal in two, a mass
      with curvilinear calcifications in one, and heterogeneous calcifications in four.
      Four patients underwent surgical excision of a palpable mass, one patient had
      complete excision of calcifications with large core biopsy technique, and three
      patients had stereotactic vacuum-assisted mammotome biopsy (VAMB). MFN should be
      included in the differential diagnosis of lesions in a breast with previous
      trauma or surgery. A minimally invasive diagnostic procedure should be considered
      in order to avoid excessive excisional surgery.

PMID- 15569207
TI  - Phase II study of weekly paclitaxel for docetaxel-resistant metastatic breast
      cancer in Japan.
AB  - The purpose of the study was to evaluate the efficacy of weekly paclitaxel (PTX)
      against metastatic breast cancer (MBC) that was resistant to docetaxel (DTX)
      given every 3 weeks. A multicenter phase II study was performed. Women with MBC
      resistant to DTX were eligible for enrollment. DTX resistance was defined as no
      tumor response to DTX and stable disease, partial response, or complete response
      to DTX preceding disease progression. PTX 80 mg/m(2) was administered over 1 hour
      once a week for 3 weeks per 4-week cycle. Among 47 enrolled patients, 46 patients
      were assessable for response and toxicity. The overall objective response rate
      (complete responses [CRs] and partial responses [PRs]) was 17.4% and overall
      clinical benefit rate (CRs, PRs, and stable disease >or=24 weeks) was 26.1%. The
      median time to progression was 11 weeks. There were a few severe hematologic
      toxicities related to the therapy, with grade 4 neutropenia (4.3%) and
      thrombocytopenia (2.2%). Grade 3 anaphylaxis and grade 3 neuropathy were observed
      in one patient (2.2%) each. The median delivered dose intensity was 77.6
      mg/m(2)/week, 97.1% of the planned dose intensity. Weekly PTX has activity in
      patients with MBC resistant to DTX every 3 weeks.

PMID- 15569208
TI  - Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol
      17beta.
AB  - Among the endocrine factors associated with breast cancer, estrogens are
      considered to play a central role in human breast carcinogenesis. Breast cancer
      risks are increased by long-term exposure to estrogens. Zeranol (Ralgro) is a
      nonsteroidal agent with estrogenic activity that is used as a growth promoter in
      the U.S. beef and veal industry. To determine whether zeranol and estradiol
      17beta play a role in the neoplastic transformation of human breast and to
      compare the estrogenic potency of zeranol to that of estradiol-17beta in human
      breast, we treated human breast epithelial cell MCF-10A with different doses of
      zeranol or estradiol-17beta for 10 repeated treatment cycles. By utilizing the
      doubling time assay, soft agar assay, and reverse transcriptase polymerase chain
      reaction (RT-PCR) assay, we showed that 10 repeated estradiol-17beta or zeranol
      treatment cycles to MCF-10A cells decrease the doubling time of the cells by 30
      to 40% and stimulate colony formation in soft agar and induce estrogen receptor
      beta (ER-beta) mRNA expression, all of which are not dose related in our tested
      dose range. Furthermore, we show that zeranol and estradiol-17beta have a similar
      potency in the stimulation and inhibition of gene expressions in human breast
      cancer cell line MCF-7 by RT-PCR. These results indicate that both zeranol and
      estradiol-17beta can induce human breast epithelial cell neoplastic
      transformation with similar potency in the long-term exposure through the
      oxidation-reduction (redox) pathway and/or ER-beta-mediated pathway.

PMID- 15569209
TI  - Observations on the pathologic diagnosis of selected unusual lesions in needle
      core biopsies of breast.
AB  - Pathologic diagnoses rendered on needle core biopsies of mammary lesions are
      primary determinants of further intervention. Such biopsies are being performed
      for an ever-widening range of diseases in an attempt to reliably and efficiently
      render a diagnosis. This review is intended to provide practical guidance to
      pathologists in dealing with selected unusual lesions encountered in these
      biopsies. Herein we offer advice on avoiding common diagnostic errors and on
      considering the relevant differential diagnosis of mucocele-like lesions, spindle
      cell metaplastic carcinoma, adenomyoepithelioma, pseudoangiomatous stromal
      hyperplasia (PASH), collagenous spherulosis, myofibroblastoma, vascular lesions,
      and lymphoid infiltrates in the breast.

PMID- 15569210
TI  - Granular cell tumor of the breast: a series of 17 cases and review of the
      literature.
AB  - Seventeen cases of granular cell tumor (GCT) of the breast are reviewed. The
      demographics and clinical features are reviewed and the radiologic and pathologic
      features as well as the immunohistochemistry are discussed. To our knowledge, our
      series of 17 breast GCT cases represent the largest series published to date.

PMID- 15569211
TI  - Intramedullary spinal cord metastasis in breast cancer: clinical features,
      diagnosis, and therapeutic consideration.
AB  - Intramedullary spinal cord metastases (ISCMs) are very rare, but can cause
      devastating complications from underlying breast cancer. We report the case of a
      woman with known metastatic breast cancer and progressive neurologic
      deterioration caused by an ISCM. The epidemiology, pathogenesis, clinical
      presentation, diagnostic considerations, and therapeutic options are discussed.

PMID- 15569212
TI  - Recurrent abscess after MammoSite brachytherapy.
AB  - Recently a new catheter was introduced to facilitate brachytherapy in a
      lumpectomy cavity. Data are limited on the side effects of high-dose
      brachytherapy to the lumpectomy cavity with the MammoSite catheter. We present a
      case of recurrent abscesses over a 7-month period in the lumpectomy cavity after
      MammoSite brachytherapy.

PMID- 15569213
TI  - Ultrasound demonstration of clip migration to Skin within 6 weeks of 11-gauge
      vacuum-assisted stereotactic breast biopsy.
AB  - A 39-year-old woman underwent 11-gauge vacuum-assisted stereotactic biopsy of a
      cluster of calcifications at the 5 o'clock location in the left breast. Initial
      clip placement was confirmed by mammograms to be at the biopsy site. The patient
      experienced episodic minimal bleeding at the skin entry site when she went home.
      The patient presented 6 weeks later with a history of progressive discomfort and
      lump at the stereotactic breast biopsy scar site. Ultrasound confirmed clip
      migration to the skin incision site. The clip was removed percutaneously by the
      radiologist, relieving the patient of her symptoms.

PMID- 15569214
TI  - Analysis of nipple-areolar complex involvement with mastectomy: can the nipple be
      preserved in egyptian patients receiving skin-sparing mastectomy?

PMID- 15569215
TI  - A giant cystosarcoma phyllodes.

PMID- 15569216
TI  - Infiltrating carcinoma with medullary features in the male breast: imaging and
      pathologic findings.

PMID- 15569217
TI  - Gynecomastia-like Changes in the female breast.

PMID- 15569218
TI  - Distinctive calcific deposits in pregnancy-like hyperplasia.

PMID- 15569219
TI  - Stiff-person syndrome: a rare presentation for breast cancer.

PMID- 15569220
TI  - Multidisciplinary breast unit: the activity of the past 15 years.

PMID- 15569221
TI  - Mammary parenchymal angiosarcoma after breast-conserving treatment for invasive
      high-grade ductal carcinoma.

PMID- 15569222
TI  - Midwifery students and breast self-examination.

PMID- 15569224
TI  - Principles of antimicrobial therapy in the transplant patient.

PMID- 15569225
TI  - Valganciclovir prophylaxis in patients at high risk for the development of
      cytomegalovirus disease.
AB  - BACKGROUND: Despite advances in antiviral therapies, cytomegalovirus (CMV)
      remains the leading opportunistic infection in the transplant population.
      Valganciclovir (VGC), the L-valyl ester prodrug of ganciclovir (GCV), provides an
      excellent oral alternative to GCV for the prevention of CMV in transplant
      recipients. We investigated the use of VGC for CMV prevention in high-risk renal
      and pancreas transplant recipients. METHODS: Patients at high risk for
      development of CMV disease were defined as either those who had donor positive,
      recipient-negative serostatus (D+/R-), or those who received antilymphocyte
      antibody (ALA) therapy for either rejection treatment or induction. A
      retrospective review was conducted of all kidney and pancreas transplants
      performed between August 2001 and December 2003. A total of 341 transplants were
      performed, of which 109 received VGC, and 88 were included in this analysis.
      RESULTS: The overall incidence of CMV disease was 5.7% (5/88). All of the CMV
      episodes were in patients who were D+/R- (17.2% [5/29] versus 0% [0/59],
      P<0.001). Of these patients, all the episodes of CMV were in patients who
      received VGC prophylaxis for<100 days post transplant (29% [5/17] versus 0%
      [0/12], P=0.06). The overall incidence of leukopenia was 11% and thrombocytopenia
      was 7%, with the incidence between the D+/R- group and the ALA group being
      similar. CONCLUSION: VGC is an effective agent in preventing CMV disease in
      kidney and pancreas transplant recipients who are at high risk for developing the
      disease. The optimal length of prophylaxis in D+/R- patients is still undefined,
      while 3 months of prophylaxis appears to be sufficient in patients who received
      ALA therapy.

PMID- 15569226
TI  - Retrospective study of the hepatic safety profile of patients concomitantly
      treated with caspofungin and cyclosporin A.
AB  - BACKGROUND: Mild, transient alanine aminotransferase (ALT) elevations were seen
      in Phase I studies of caspofungin and cyclosporin A (CsA). METHODS: We conducted
      a retrospective chart review at four sites to characterize the hepatic safety in
      patients receiving > or =1 day of both drugs over a 20-month period.
      Investigators assessed reasons for discontinuing concomitant therapy and the
      presence/etiology of any hepatotoxicity. RESULTS: Forty patients receiving
      concomitant therapy for 1-290 days (median 17.5 days) were identified. Although
      common, liver enzyme abnormalities were frequently attributed to other
      comorbidities or medications. ALT and/or aspartate aminotransferase (AST)
      elevations occurred in 14 patients (35%). Five had AST elevations at least
      possibly related to caspofungin/CsA, but none were >3.6 times the normal upper
      limit. No ALT elevations were related to caspofungin/CsA. Two of 4 patients had
      discontinuation of therapy because of hepatotoxicity possibly related to
      caspofungin/CsA. No serious adverse events occurred because of caspofungin.
      CONCLUSIONS: These data do not suggest a significant risk of clinically relevant
      hepatotoxicity with concomitant caspofungin/CsA.

PMID- 15569227
TI  - Successful treatment of vancomycin-resistant Enterococcus faecium endocarditis
      with linezolid in a renal transplant recipient with human immunodeficiency virus
      infection.
AB  - Infections with vancomycin-resistant Enterococci cause significant morbidity and
      mortality in hospitalized patients, including transplant recipients. We report
      the successful use of oral linezolid to treat a case of vancomycin-resistant
      Enterococcus faecium endocarditis in a renal transplant recipient with human
      immunodeficiency virus infection.

PMID- 15569228
TI  - Multiple giant molluscum contagiosum in a renal transplant recipient.
AB  - Atypical presentations of molluscum contagiosum (MC) infection can be expected in
      renal transplant recipients, as a result of long-term immunosuppression. However,
      giant MC has rarely been reported in this population. We present a 28-year-old
      female renal transplant recipient receiving immunosuppressive therapy who
      developed multiple giant MC lesions on her axillary folds. The lesions were
      treated successfully with curettage and electrocauterization.

PMID- 15569229
TI  - Lethal cytomegalovirus ischemic colitis presenting with fever of unknown origin.
AB  - We report a fatal case of cytomegalovirus (CMV) ischemic colitis in a renal
      transplant recipient. The disease was manifested with fever of unknown origin for
      27 days followed by progressive right lower abdominal pain. The clinical
      condition deteriorated rapidly with development of disseminated intravascular
      coagulopathy and internal bleeding despite right hemicolectomy and antiviral
      therapy. The patient died 11 days after the onset of abdominal pain. We conclude
      that the possibility of CMV ischemic colitis should be suspected if a patient
      presents with fever and abdominal pain in the early months after transplantation,
      and that early viral detection by CMV polymerase chain reaction can be
      lifesaving.

PMID- 15569230
TI  - Aspergillus mediastinitis following orthotopic heart transplantation: case report
      and review of the literature.
AB  - Bacterial mediastinitis after orthotopic heart transplantation (OHT) is well
      described in the literature. However, little information has been published on
      fungal mediastinitis in this population. We describe a man with Aspergillus
      fumigatus mediastinitis diagnosed 10 weeks after OHT. The patient was treated
      with voriconazole. The literature on Aspergillus mediastinitis is also reviewed.

PMID- 15569231
TI  - Successful kidney re-transplantation in a patient with previous allograft kidney
      tuberculosis.
AB  - Opportunistic infections, and in particular tuberculosis (TB), carry substantial
      morbidity and mortality in solid organ transplant recipients. We report a 39-year
      old man who underwent a cadaveric renal transplant. Three months postoperatively,
      he was diagnosed to have tuberculous infection of his graft kidney manifested as
      fever and renal impairment. The diagnosis was confirmed by renal biopsy, which
      showed granuloma formation and positive stain for acid-fast bacilli (AFB). His
      systemic symptoms responded well to a complete course of anti-tuberculous
      therapy, but his renal function continued to deteriorate. Graft nephrectomy was
      performed and the patient underwent a second kidney transplant 1 year later. He
      remained well and asymptomatic thereafter. No signs of recurrence of tuberculous
      infection were noted up until the present time. This case illustrates that TB
      remains an important threat to transplant recipients. Although reactivation of
      dormant TB is the usual mode of infection, acquisition from the donor graft is
      also possible. The latter may account for the infection in our case, as our
      patient had a negative tuberculin skin test and normal chest radiograph prior to
      transplant. The identification of AFB in the kidney graft less than 3 months
      postoperatively also suggested that causal relationship. While diagnosing TB in
      post-transplant recipients is difficult and may require renal biopsy, as in our
      case, treatment on the other hand is no different from the standard protocols.
      However, no consensus has been reached on the safety of re-transplantation. Also,
      the need for graft nephrectomy and chemoprophylaxis remains unclear.

PMID- 15569232
TI  - Polyomaviruses and transplant patients: new concepts.

PMID- 15569233
TI  - A novel method for the detection of bacteria in platelet concentrates utilizing
      oxygen consumption as a marker for bacterial growth.
AB  - Bacterial transfusion-transmission remains a significant problem in transfusion
      medicine. Diversion and improved donor arm disinfection has been introduced by
      blood services to reduce bacterial transmissions. These interventions are not
      100% effective and, therefore, there is still a requirement to screen blood
      donations, particularly platelet concentrates which are responsible for the
      majority of transmissions. Pall BDS, a novel bacterial testing system, detects
      the presence of bacteria in platelet concentrates by measuring the reduction in
      oxygen content associated with bacterial growth. Buffy coat-derived pooled
      platelet concentrates were spiked with 12 aerobic and two anaerobic organisms
      (one species per bag, n = 10) at 100-700 cfu mL(-1). Samples were taken into Pall
      BDS sample pouches and incubated for 0, 24, 30 and 48 h. An initial incubation
      was undertaken at 35 degrees C for 24 h and subsequent incubation was at 22
      degrees C. At the end of the incubation period the oxygen content in the Pall BDS
      pouches was measured using a gas analyser. An oxygen content less than or equal
      to 19.5% was deemed to be positive. Pall BDS pouches tested positive in 80, 94
      and 98% units spiked with aerobic bacteria at 24, 30 and 48 h, respectively.
      Anaerobic bacteria were not detected by the system. Positive BDS pouches
      contained 10(6) cfu mL(-1) or greater. The system was simple and easy to perform.
      Pall BDS has a closed sampling system which prevents exogenous contamination.
      This initial study indicates that the Pall BDS offers a practicable system for
      detecting bacteria present in leucodepleted platelet concentrates.

PMID- 15569234
TI  - The natural history of maternal immunization against foetal platelet
      alloantigens.
AB  - Foetomaternal alloimmune thrombocytopenia (FMAIT) occurs when maternal antibodies
      of an antigen-negative mother cause destruction of sensitized foetal platelets.
      In Caucasian populations, 6-12% of human platelet antigen (HPA)-1a-negative women
      develop anti-HPA-1a, and the incidence of clinically affected cases is estimated
      to be 10-20% of immunized women. This study was performed in order to elucidate
      the rate of maternal immunization, incidence of FMAIT and the likely outcome of
      the condition in Asians. Excluding two or more pregnancies during the period,
      serum samples from 24 630 pregnant women, mainly Japanese, were screened for
      antibodies against platelet alloantigens by means of mixed passive
      haemagglutination (MPHA) (Anti-HPA-MPHA, Olympus, Tokyo). Antibodies were
      detected in 0.91% (223/24 630) of the women's samples and the immunization rate
      was correlated with the number of pregnancies. Antibody specificity included anti
      HPA-4b (49), anti-HPA-5a (three), anti-HPA-5b (168), anti-HPA-4b + 5b (one) and
      anti-Nak(a) (CD36) (two). No alloimmunization was observed within the HPA-1, HPA
      2, HPA-3 or HPA-6 systems. Among HPA-4b- or HPA-5b-negative women, 24% or 14%
      estimated, respectively, had antibodies and 26% (10/38) or 10% (12/125) of
      neonates, respectively, born to these mothers developed thrombocytopenia. Two
      neonates born to mothers having anti-HPA-4b developed generalized purpura. No
      cases of intracranial bleeding or death due to FMAIT were recorded. Generalized
      purpura due to FMAIT occurs in one in 9359 (95% CI: 1 in 77 519-1 in 2591)
      pregnancies solely because of HPA-4b incompatibility.

PMID- 15569235
TI  - Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet
      concentrates in proven or suspected platelet alloimmunization.
AB  - The optimal treatment of neonatal alloimmune thrombocytopenia (NAIT) is the
      transfusion of compatible donor platelets. The National Blood Service in England
      has established panels of "accredited" donors negative for human platelet
      antigens HPA-1a and HPA-5b, the most commonly implicated alloantigens. We have
      retrospectively surveyed the frequency of use and clinical effectiveness of
      donations collected over a 13-month period from the Oxford accredited panel.
      Ninety-five per cent of hyperconcentrated platelets (HPCs) collected were issued,
      all for intrauterine transfusion to fetuses at risk of NAIT due to the presence
      of maternal platelet alloantibodies and previously affected siblings. Thirty-one
      per cent of paediatric platelet concentrates (PPCs) collected were issued, of
      which 57% were used for cases of suspected NAIT. Fifty-four per cent of adult
      therapeutic doses collected were issued; 5% of these were used in cases of
      suspected NAIT or proven post-transfusion purpura (PTP). Good increments were
      seen in most NAIT cases transfused with HPCs or PPCs, and a moderate increment in
      the one PTP case. We conclude that the establishment of accredited panels is
      justified and enables delivery of a clinically effective treatment for NAIT.
      Increased use and cost-effectiveness could be achieved by the delivery of an
      educational programme to neonatal unit clinical staff to increase the awareness
      and appropriate treatment of NAIT.

PMID- 15569236
TI  - Neonatal alloimmune thrombocytopenia due to an antibody against a labile
      component of human platelet antigen-3b (Bak b).
AB  - We report the second case of neonatal alloimmune thrombocytopenia due to anti
      human platelet antigen (HPA)-3b (Bak(b)) antibody. The infant was severely
      affected with intracranial haemorrhage. Most importantly, we were able to detect
      this antibody only by using fresh, unfixed platelets as antigen. This antibody
      was detectable neither by conventional mixed passive haemagglutination, platelet
      immunofluorescence test using fixed platelets, nor by monoclonal antigen
      immobilization of platelet antigen assay using solubilized platelets. We assume
      that this antibody reacts only with fresh platelets and that the antigen is a
      labile component of HPA-3b (Bak(b)).

PMID- 15569237
TI  - Real-time PCR genotyping of human platelet alloantigens HPA-1, HPA-2, HPA-3 and
      HPA-5 is superior to the standard PCR-SSP method.
AB  - Genotyping of the human platelet alloantigens (HPA) is useful for the diagnosis
      and therapy of the patients with alloimmune thrombocytopenic syndromes, such as
      post-transfusion refractoriness to platelets, post-transfusion thrombocytopenic
      purpura and foetomaternal alloimmune thrombocytopenia. We have developed,
      optimized and validated a new method for simultaneous genotyping of HPAs - HPA-1,
      HPA-2, HPA-3 and HPA-5 - by using the real-time polymerase chain reaction (PCR)
      based on TaqMan technology. Its performances were compared to those of the
      standard PCR-sequence-specific primers (SSP) method by testing 120 DNA samples.
      Several discrepancies between the two methods have been observed, especially in
      the HPA-3 genotyping. Evidently, the PCR-SSP method produced several false
      positive results due to its technical drawbacks. Based on our comparison, we
      believe that the new real-time TaqMan PCR assay for the HPA-1, HPA-2, HPA-3 and
      HPA-5 genotyping is faster, more reliable and reproducible, compared to the
      standard PCR-SSP.

PMID- 15569238
TI  - Gene frequencies of the HPA-15 (Gov) platelet alloantigen system in Brazilians.
AB  - The HPA-15 (Gov) alloantigen is a biallelic co-dominant system on human
      platelets, and its allele HPA-15a and HPA-15b differ by an A-->C single
      nucleotide polymorphism at nucleotide 2108 of the coding sequence resulting in a
      Tyr682Ser substitution in the mature CD109 glycoprotein. Employing the polymerase
      chain reaction-restriction fragment length polymorphism technique, we determined
      the HPA-15 gene frequencies among 276 subjects of distinct Brazilian ethnic
      groups including, 15 Caucasians, 15 African Brazilians, 15 Orientals, 106 Amazon
      Xikrin Indians, 31 Amazon Gavioes Indians and 94 blood donors. The calculated HPA
      15a and HPA-15b allele frequencies found in Caucasians (0.53/0.47), African
      Brazilians (0.57/0.43), Orientals (0.57/0.43) and Brazilian blood donors
      (0.52/0.48) did not differ significantly. However, the HPA-15a and HPA-15b gene
      frequencies of Xikrin Indians (0.78/0.22) were significantly different from that
      of all other groups (P < 0.01). The HPA-15a/a, HPA-15a/b and HPA-15b/b genotype
      frequencies observed in Gavioes Indians were significantly different from those
      seen in African Brazilians (P = 0.04) and blood donors (P = 0.017). The present
      data showed that the distribution of the HPA-15 (Gov) system alleles observed
      among the Brazilian population is quite similar to the distributions already
      reported among Asian, Canadian and European populations. Moreover, the data
      indicated differences in the frequency of the HPA-15 system between Amazon
      Indians and other distinct Brazilian ethnic groups suggesting that Amerindians
      would be at higher risk of HPA-15 alloimmunization in the need of receiving blood
      components collected from blood donors of other ethnic groups.

PMID- 15569240
TI  - A protein's final ESCRT.
AB  - In eukaryotic cells, delivery of transmembrane proteins into the lumen of the
      lysosome for degradation is mediated by the multivesicular body pathway. The
      function of the ESCRT protein complexes is required for both the formation of
      multivesicular body lumenal vesicles and the sorting of endosomal cargo proteins
      into these vesicles. Recent studies have identified additional factors that seem
      to function as an upstream cargo retention system feeding into the ESCRT
      machinery, given new insights into the dynamic structure of multivesicular
      bodies, and identified a potential mechanism for multivesicular body vesicle
      formation.

PMID- 15569241
TI  - Exosomes: a bubble ride for prions?
AB  - In certain cell types, endosomal multivesicular bodies may fuse with the cell
      surface in an exocytic manner. During this process, the small 50-90-nm-diameter
      vesicles contained in their lumen are released into the extracellular
      environment. The released vesicles are called exosomes. Exosome secretion can be
      used by cells to eject molecules targeted to intraluminal vesicles of
      multivesicular bodies, but particular cell types exploit exosomes as
      intercellular communication devices for transfer of proteins and lipids between
      cells. The molecular composition of exosomes is determined by sorting events
      within endosomes that occur concomitantly with the generation of intraluminal
      vesicles. As other raft-associated components, the glycosylphosphatidylinositol
      linked prion protein transits through multivesicular bodies. Recent findings in
      non-neuronal cell models indicate prion protein association with secreted
      exosomes. Thus, exosomes could constitute vehicles for transmission of the
      infectious prion protein, bypassing cell-cell contact in the dissemination of
      prions.

PMID- 15569243
TI  - Structure and dynamics of the Golgi complex at 15 degrees C: low temperature
      induces the formation of Golgi-derived tubules.
AB  - Immunofluorescence and cryoimmunoelectron microscopy were used to examine the
      morphologic and functional effects on the Golgi complex when protein transport is
      blocked at the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) in
      HeLa cells incubated at low temperature (15 degrees C). At this temperature, the
      Golgi complex showed long tubules containing resident glycosylation enzymes but
      not matrix proteins. These Golgi-derived tubules also lacked anterograde (VSV-G)
      or retrograde (Shiga toxin) cargo. The formation of tubules was dependent on both
      energy and intact microtubule and actin cytoskeletons. Conversely, brefeldin A or
      cycloheximide treatments did not modify the appearance. When examined at the
      electron microscope, Golgi stacks were long and curved and appeared connected to
      tubules immunoreactive to galactosyltransferase antibodies but devoid of Golgi
      matrix proteins. Strikingly, COPI proteins moved from membranes to the cytosol at
      15 degrees C, which could explain the formation of tubules.

PMID- 15569242
TI  - Covert operations of uropathogenic Escherichia coli within the urinary tract.
AB  - Entry into host cells is required for many bacterial pathogens to effectively
      disseminate within a host, avoid immune detection and cause disease. In recent
      years, many ostensibly extracellular bacteria have been shown to act as
      opportunistic intracellular pathogens. Among these are strains of uropathogenic
      Escherichia coli (UPEC), the primary causative agents of urinary tract infections
      (UTIs). UPEC are able to transiently invade, survive and multiply within the host
      cells and tissues constituting the urinary tract. Invasion of host cells by UPEC
      is promoted independently by distinct virulence factors, including cytotoxic
      necrotizing factor, Afa/Dr adhesins, and type 1 pili. Here we review the diverse
      mechanisms and consequences of host cell invasion by UPEC, focusing also on the
      impact of these processes on the persistence and recurrence of UTIs.

PMID- 15569244
TI  - The cargo in vacuolar storage protein transport vesicles is stratified.
AB  - Developing pea seeds contain two functionally distinct vacuoles--lytic vacuoles
      and protein storage vacuoles (PSV). The Golgi apparatus of these cells has to
      discriminate between proteins destined for these vacuolar compartments. Whereas
      it is known that sorting into the lytic vacuole is performed via the conserved
      clathrin-coated vesicle pathway, sorting of proteins into the protein storage
      vacuole remains enigmatic. In developing pea cotyledons, the major storage
      proteins are sorted via 'dense vesicles'. In this report we examined the sorting
      of a minor protein of the protein storage vacuole, the sucrose-binding-protein
      homolog (SBP), along the secretory pathway employing immunoelectron microscopy on
      cryosectioned pea cotyledons. SBP follows the same vesicular route into the PSV
      as the main storage proteins legumin and vicilin, via the dense-vesicles.
      Furthermore, legumin and SBP are sorted together into the same dense vesicle
      population at the stack. Although soluble cargo proteins of the dense vesicles,
      they show a stratified distribution in the lumen of the dense vesicles. Whereas
      the legumin label is equally distributed across the lumen, the SBP label is
      concentrated at the membrane of the vesicle. This observation is discussed with
      respect to a putative receptor-mediated sorting of the proteins into the dense
      vesicles.

PMID- 15569245
TI  - Starvation triggers the delivery of the endoplasmic reticulum to the vacuole via
      autophagy in yeast.
AB  - Autophagy is a survival mechanism necessary for eukaryotic cells to overcome
      nutritionally challenged environments. When autophagy is triggered, cells degrade
      nonselectively engulfed cytosolic proteins and free ribosomes that are evenly
      distributed throughout the cytoplasm. The resulting pool of free amino acids is
      used to sustain processes crucial for survival. Here we characterize an
      autophagic degradation of the endoplasmic reticulum (ER) under starvation
      conditions in addition to cytosolic protein degradation. Golgi membrane protein
      was not engulfed by the autophagosome under the same conditions, indicating that
      the uptake of ER by autophagosome was the specific event. Although the ER exists
      in a network structure that is mutually connected and resides predominantly
      around the nucleus and beneath the plasma membrane, most of autophagosome
      engulfed ER. The extent of the ER uptake by autophagy was nearly identical to
      that of the soluble cytosolic proteins. This phenomenon was explained by the
      appearance of fragmented ER membrane structures in almost all autophagosomes.
      Furthermore, ER dynamism is required for this process: ER uptake by
      autophagosomes occurs in an actin-dependent manner.

PMID- 15569246
TI  - Atg8 is essential for macropexophagy in Hansenula polymorpha.
AB  - We have isolated a peroxisome-degradation-deficient (pdd) mutant of the
      methylotrophic yeast Hansenula polymorpha via gene tagging mutagenesis.
      Sequencing revealed that the mutant was affected in the HpATG8 gene. HpAtg8 is a
      protein with high sequence similarity to both Pichia pastoris and Saccharomyces
      cerevisiae Atg8 and appeared to be essential for selective peroxisome degradation
      (macropexophagy) and nitrogen-limitation induced microautophagy. Fluorescence
      microscopy revealed that a GFP.Atg8 fusion protein was located close to the
      vacuole. After induction of macropexophagy, the GFP.Atg8 containing spot extended
      to engulf an individual peroxisome. In cells of a constructed deletion strain,
      sequestration of individual organelles was never completed; analysis of series of
      serial sections revealed that invariably a minor diaphragm-like opening remained.
      We hypothesize that H. polymorpha Atg8 facilitates sealing of the sequestering
      membranes during selective peroxisome degradation.

PMID- 15569247
TI  - Tyrosine hydroxylase phosphorylation: regulation and consequences.
AB  - The rate-limiting enzyme in catecholamine synthesis is tyrosine hydroxylase. It
      is phosphorylated at serine (Ser) residues Ser8, Ser19, Ser31 and Ser40 in vitro,
      in situ and in vivo. A range of protein kinases and protein phosphatases are able
      to phosphorylate or dephosphorylate these sites in vitro. Some of these enzymes
      are able to regulate tyrosine hydroxylase phosphorylation in situ and in vivo but
      the identity of the kinases and phosphatases is incomplete, especially for
      physiologically relevant stimuli. The stoichiometry of tyrosine hydroxylase
      phosphorylation in situ and in vivo is low. The phosphorylation of tyrosine
      hydroxylase at Ser40 increases the enzyme's activity in vitro, in situ and in
      vivo. Phosphorylation at Ser31 also increases the activity but to a much lesser
      extent than for Ser40 phosphorylation. The phosphorylation of tyrosine
      hydroxylase at Ser19 or Ser8 has no direct effect on tyrosine hydroxylase
      activity. Hierarchical phosphorylation of tyrosine hydroxylase occurs both in
      vitro and in situ, whereby the phosphorylation at Ser19 increases the rate of
      Ser40 phosphorylation leading to an increase in enzyme activity. Hierarchical
      phosphorylation depends on the state of the substrate providing a novel form of
      control of tyrosine hydroxylase activation.

PMID- 15569248
TI  - Proteasome inhibitors suppress formation of polyglutamine-induced nuclear
      inclusions in cultured postmitotic neurons.
AB  - At least nine neurodegenerative disorders are caused by expansion of
      polyglutamine repeats in various genes. This expansion induces the formation of
      nuclear inclusions (NI) within various cell types. In this study, we developed a
      model for polyglutamine diseases using primary cultures of sympathetic neurons
      from the superior cervical ganglia of prenatal rat pups. Transfection with a
      plasmid encoding 127 glutamine repeats causes NI to develop in approximately 70%
      of the sympathetic neurons within 6 days. In addition, it causes somatic atrophy
      and inhibits dendritic growth. The NIs contain ubiquitinated proteins and
      sequester the molecular chaperone heat shock protein 70 (Hsp70). We found that
      two specific proteasome inhibitors, lactacystin and CEP1612, suppress
      thezformation of polyglutamine-induced NI. In addition, lactacystin treatment
      induced the removal of preexisting NI. Western blotting and immunocytochemistry
      revealed that lactacystin and CEP1612 strongly induce the expression of Hsp70,
      whereas less specific proteasome inhibitor such as N-acetyl-Leu-Leu-Norleucinal
      does not. Coexpression of 127 glutamines with a plasmid encoding wild-type Hsp70
      gene resulted in a marked reduction of the percentage of neurons containing NI.
      In addition, transfection with plasmids encoding mutant Hsp70 blocked the effects
      of lactacystin. These findings further implicate Hsp70 as a neuroprotective
      molecule and they suggest the potential utility of certain proteasome inhibitors
      in the treatment of polyglutamine diseases.

PMID- 15569249
TI  - Low nNOS protein in the locus coeruleus in major depression.
AB  - Disruptions of glutamatergic and noradrenergic signaling have been postulated to
      occur in depressive disorders. Glutamate provides excitatory input to the
      noradrenergic locus coeruleus (LC). In this study, the location of
      immunoreactivity against neuronal nitric oxide synthase (nNOS), an intracellular
      mediator of glutamate receptor activation, was examined in the normal human LC,
      and potential changes in nNOS immunoreactivity that might occur in major
      depression were evaluated. Tissue containing LC, and a non-limbic, LC projection
      area (cerebellum) was obtained from 11 to 12 matched pairs of subjects with major
      depression and control subjects lacking major psychiatric diagnoses. In the LC
      region, nNOS immunoreactivity was found in large neuromelanin-containing neurons,
      small neurons lacking neuromelanin, and glial cells. Levels of nNOS
      immunoreactivity were significantly lower in the LC (- 44%, p < 0.05), but not in
      the cerebellum, when comparing depressed with control subjects. nNOS levels were
      positively correlated with brain pH values in depressed, but not control,
      subjects in both brain regions. Low levels of nNOS in the LC may reflect altered
      excitatory input to this nucleus in major depression. However, pH appears to
      effect preservation of nNOS immunoreactivity in subjects with depression. This
      factor may contribute, in part, to low levels of nNOS in depression.

PMID- 15569250
TI  - Chemotherapy-induced cell death in primary cerebellar granule neurons but not in
      astrocytes: in vitro paradigm of differential neurotoxicity.
AB  - The nervous system is frequently the site of symptomatic toxicity of
      antineoplastic agents. However, there is limited information about the
      differential vulnerability of neurons, astrocytes and glioma cells. We have
      analyzed the effects of four chemotherapeutic drugs (lomustine, cisplatin,
      topotecan and vincristine) on primary cerebellar granule neurons and astrocytes
      derived from rats. All drugs led to cell death in cerebellar granule neurons in a
      concentration-dependent manner. Comparison of the EC50 values for cerebellar
      neurons and astrocytes with the median EC50 values of 12 malignant glioma cell
      lines demonstrated a large therapeutic range for lomustin and cisplatin. Further,
      this comparison revealed a 100-fold higher sensitivity of cerebellar neurons
      towards vincristine and 10-fold higher sensitivity towards topotecan compared
      with glioma cells. Astrocytes were generally resistant to vincristine. In
      cerebellar granule neurons, vincristine and to a lesser extent topotecan induced
      caspase 3 and caspase 9 cleavage, and enhanced caspase activity and Akt-dependent
      expression of phosphorylated BAD. zVAD-fmk, a caspase inhibitor and brain-derived
      neurotrophic factor (BDNF), but not MK-801, a non-competitive NMDA receptor
      antagonist, significantly reduced vincristine- or topotecan-induced cell death.

PMID- 15569251
TI  - Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms.
AB  - We have investigated the ability of pramipexole, a dopamine agonist used in the
      symptomatic treatment of Parkinson's disease (PD), to protect against cell death
      induced by 1-methyl-4-phenylpyridinium (MPP+) and rotenone in dopaminergic and
      non-dopaminergic cells. Pre-incubation with either the active (-)- or inactive
      (+)-enantiomer forms of pramipexole (10 microm) decreased cell death in response
      to MPP+ and rotenone in dopaminergic SHSY-5Y cells and in non-dopaminergic JK
      cells. The protective effect was not prevented by dopamine receptor blockade
      using sulpiride or clozapine. Protection occurred at concentrations at which
      pramipexole did not demonstrate antioxidant activity, as shown by the failure to
      maintain aconitase activity. However, pramipexole reduced caspase-3 activation,
      decreased the release of cytochrome c and prevented the fall in the mitochondrial
      membrane potential induced by MPP+ and rotenone. This suggests that pramipexole
      has anti-apoptotic actions. The results extend the evidence for the
      neuroprotective effects of pramipexole and indicate that this is not dependent on
      dopamine receptor occupation or antioxidant activity. Further evaluation is
      required to determine whether the neuroprotective action of pramipexole is
      translated to a disease-modifying effect in PD patients.

PMID- 15569252
TI  - Biochemical and structural brain alterations in female mice with cerebral
      pyruvate dehydrogenase deficiency.
AB  - Pyruvate dehydrogenase complex (PDC) deficiency is an inborn metabolic disorder
      associated with a variety of neurologic abnormalities. This report describes the
      development and initial characterization of a novel murine model system in which
      PDC deficiency has been introduced specifically into the developing nervous
      system. The absence of liveborn male and a roughly 50% reduction in female
      offspring following induction of the X-linked mutation indicate that extensive
      deficiency of PDC in the nervous system leads to pre-natal lethality. Brain
      tissue from surviving females at post-natal days 15 and 35 was shown to have
      approximately 75% of wild-type PDC activity, suggesting that a threshold of
      enzyme activity exists for post-natal survival. Detailed histological analyses of
      brain tissue revealed structural defects such as disordered neuronal
      cytoarchitecture and neuropil fibers in grey matter, and reduced size of bundles
      and disorganization of fibers in white matter. Many of the histologic
      abnormalities resemble those found in human female patients who carry mutations
      in the X-linked ortholog. These findings demonstrate a requirement for PDC
      activity within the nervous system for survival in utero and suggest that
      impaired pyruvate metabolism in the developing brain can affect neuronal
      migration, axonal growth and cell-cell interactions.

PMID- 15569253
TI  - Identification and characterization of a Ca2+ -sensitive interaction of the
      vanilloid receptor TRPV1 with tubulin.
AB  - The vanilloid receptor TRPV1 plays a well-established functional role in the
      detection of a range of chemical and thermal noxious stimuli, such as those
      associated with tissue inflammation and the resulting pain. TRPV1 activation
      results in membrane depolarization, but may also trigger intracellular Ca2+ 
      signalling events. In a proteomic screen for proteins associated with the C
      terminal sequence of TRPV1, we identified beta-tubulin as a specific TRPV1
      interacting protein. We demonstrate that the TRPV1 C-terminal tail is capable of
      binding tubulin dimers, as well as of binding polymerized microtubules. The
      interaction is Ca2+ -sensitive, and affects microtubule properties, such as
      microtubule sensitivity towards low temperatures and nocodazole. Our data thus
      provide compelling evidence for the interaction of TRPV1 with the cytoskeleton.
      The Ca2+ -sensitivity of this interaction suggests that the microtubule
      cytoskeleton at the cell membrane may be a downstream effector of TRPV1
      activation.

PMID- 15569254
TI  - Tyramine receptor (SER-2) isoforms are involved in the regulation of pharyngeal
      pumping and foraging behavior in Caenorhabditis elegans.
AB  - Octopamine regulates essential processes in nematodes; however, little is known
      about the physiological role of its precursor, tyramine. In the present study, we
      have characterized alternatively spliced Caenorhabditis elegans tyramine receptor
      isoforms (SER-2 and SER-2A) that differ by 23 amino acids within the mid-region
      of the third intracellular loop. Membranes prepared from cells expressing either
      SER-2 or SER-2A bind [3H]lysergic acid diethylamide (LSD) in the low nanomolar
      range and exhibit highest affinity for tyramine. Similarly, both isoforms exhibit
      nearly identical Ki values for a number of antagonists. In contrast, SER-2A
      exhibits a significantly lower affinity than SER-2 for other physiologically
      relevant biogenic amines, including octopamine. Pertussis toxin treatment reduces
      affinity for both tyramine and octopamine, especially for octopamine in membranes
      from cells expressing SER-2, suggesting that the conformation of the mid-region
      of the third intracellular loop is dictated by G-protein interactions and is
      responsible for the differential tyramine/octopamine affinities of the two
      isoforms. Tyramine reduces forskolin-stimulated cAMP levels in HEK293 cells
      expressing either isoform with nearly identical IC50 values. Tyramine, but not
      octopamine, also elevates Ca2+ levels in cells expressing SER-2 and to a lesser
      extent SER-2A. Most importantly, ser-2 null mutants (pk1357) fail to suppress
      head movements while reversing in response to nose-touch, suggesting a role for
      SER-2 in the regulation of foraging behavior, and fail to respond to tyramine in
      assays measuring serotonin-dependent pharyngeal pumping. These are the first
      reported functions for SER-2. These results suggest that C. elegans contains
      tyramine receptors, that individual SER-2 isoforms may differ significantly in
      their sensitivity to other physiologically relevant biogenic amines, such as
      octopamine (OA), and that tyraminergic signaling may be important in the
      regulation of key processes in nematodes.

PMID- 15569255
TI  - Reduced MPTP toxicity in noradrenaline transporter knockout mice.
AB  - The noradrenergic neurons of the locus coeruleus (LC) are damaged in Parkinson's
      disease (PD). Neurotoxin ablation of the LC noradrenergic neurons has been shown
      to exacerbate the dopaminergic toxicity of MPTP, suggesting that the
      noradrenergic system protects dopamine neurons. We utilized mice that exhibit
      elevated synaptic noradrenaline (NA) by genetically deleting the noradrenaline
      transporter (NET), a key regulator of the noradrenergic system (NET KO mice). NET
      KO and wild-type littermates were administered MPTP and striatal dopamine
      terminal integrity was assessed by HPLC of monoamines, immmunoblotting for
      dopaminergic markers and tyrosine hydroxylase (TH) immunohistochemistry. MPTP
      significantly reduced striatal dopamine in wild-type mice, but not in the NET KO
      mice. To confirm that the protection observed in the NET KO mice was due to the
      lack of NET, we treated wild-type mice with the specific NET inhibitor,
      nisoxetine, and then challenged them with MPTP. Nisoxetine conferred protection
      to the dopaminergic system. These data indicate that NA can modulate MPTP
      toxicity and suggest that manipulation of the noradrenergic system may have
      therapeutic value in PD.

PMID- 15569256
TI  - Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15
      weeks of nutritional deprivation of n-3 polyunsaturated fatty acids.
AB  - Male rat pups (21 days old) were placed on a diet deficient in n-3
      polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing
      alpha-linolenic acid (alpha-LNA; 18 : 3n-3). After 15 weeks on a diet, [4,5
      3H]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral
      cerebral ventricle, and the rats were killed at fixed times over a period of 60
      days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced
      plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change
      thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by
      plotting log10 (DHA radioactivity) against time after tracer injection, equaled
      33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in
      phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in
      phosphatidylserine; all had a decay slope significantly greater than 0 (p <
      0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or
      greater, and calculated rates of DHA loss from brain, Jout, were reduced.
      Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and
      to do so even more effectively in the face of reduced n-3 PUFA availability for
      only 15 weeks.

PMID- 15569257
TI  - Functional characterization of mouse alpha4beta2 nicotinic acetylcholine
      receptors stably expressed in HEK293T cells.
AB  - Mouse alpha4beta2 nicotinic acetylcholine receptors (nAchRs) were stably
      expressed in HEK293T cells. The function of this stable cell line, termed
      mmalpha4beta2, was assessed using an aequorin-based luminescence method that
      measures agonist-evoked changes in intracellular calcium. Agonist-elicited
      changes in intracellular calcium were due primarily to direct entry of calcium
      through the alpha4beta2 channel, although release of calcium from intracellular
      stores contributed approximately 28% of the agonist-evoked response. Agonist
      pharmacologies were very similar between the mmalpha4beta2 cells and most cell
      lines that stably express human alpha4beta2 nAchRs. Based on agonist profiles and
      sensitivity to the antagonist dihydro-beta-erythroidine (DHbetaE), the
      predominant alpha4beta2 nAchR expressed in the mmalpha4beta2 cells exhibits a
      pharmacology that most resembles the DHbetaE-sensitive component of 86Rb+ efflux
      from mouse brain synaptosomes. However, when evaluated with the aequorin assay,
      the mmalpha4beta2 nAchR was found to be atypically sensitive to blockade by the
      presumed alpha7-selective antagonist methyllycaconitine (MLA), exhibiting an IC50
      value of 31 +/- 0.1 nm. Similar IC50 values have been reported for the MLA
      inhibition of nicotine-stimulated dopamine release, a response that is mediated
      by beta2-subunit-containing nAchRs and not alpha7-subunit-containing nAchRs.
      Consequently, at low nanomolar concentrations, MLA may not be as selective for
      alpha7-containing nAchRs as previously thought.

PMID- 15569258
TI  - Differential regulation of GLAST immunoreactivity and activity by protein kinase
      C: evidence for modification of amino and carboxyl termini.
AB  - Many neurotransmitter transporters, including the GLT-1 and EAAC1 subtypes of the
      glutamate transporter, are regulated by protein kinase C (PKC) and these effects
      are associated with changes in cell surface expression. In the present study, the
      effects of PKC activation on the glutamate aspartate transporter (GLAST) subtype
      of glutamate transporter were examined in primary astrocyte cultures. Acute (30
      min) exposure to the phorbol 12-myristate 13-acetate (PMA) increased
      (approximately 20%) transport activity but had the opposite effect on both total
      and cell surface immunoreactivity. Chronic treatment (6 or 24 h) with PMA had no
      effect on transport activity but caused an even larger decrease in total and cell
      surface immunoreactivity. This loss of immunoreactivity was observed using
      antibodies directed against three different cytoplasmic epitopes, and was blocked
      by the PKC antagonist, bisindolylmaleimide II. We provide biochemical and
      pharmacological evidence that the activity observed after treatment with PMA is
      mediated by GLAST. Two different flag-tagged variants of the human homolog of
      GLAST were introduced into astrocytes using lentiviral vectors. Although
      treatment with PMA caused a loss of transporter immunoreactivity, flag
      immunoreactivity did not change in amount or size. Together, these studies
      suggest that activation of PKC acutely up-regulates GLAST activity, but also
      results in modification of several different intracellular epitopes so that they
      are no longer recognized by anti-GLAST antibodies. We found that exposure of
      primary cultures of neurons/astrocytes to transient hypoxia/glucose deprivation
      also caused a loss of GLAST immunoreactivity that was attenuated by the PKC
      antagonist, bisindolylmaleimide II, suggesting that some acute insults previously
      thought to cause a loss of GLAST protein may mimic the phenomenon observed in the
      present study.

PMID- 15569259
TI  - Pathophysiological concentrations of amyloid beta proteins directly inhibit rat
      brain and recombinant human type II phosphatidylinositol 4-kinase activity.
AB  - We previously found that pathophysiological concentrations (< or = 10 nm) of an
      amyloid beta protein (Abeta25-35) reduced the plasma membrane
      phosphatidylinositol monophosphate level in cultured rat hippocampal neurons with
      a decrease in phosphatidylinositol 4-monophosphate-dependent Cl- -ATPase
      activity. As this suggested an inhibitory effect of Abeta25-35 on plasma membrane
      phosphatidylinositol 4-kinase (PI4K) activity, in vitro effects of Abetas on PI4K
      activity was examined using rat brain subcellular fractions and recombinant human
      type II PI4K (PI4KII). Abeta25-35 (10 nm) inhibited PI4KII activity, but neither
      PI 3-kinase (PI3K) nor type III PI4K (PI4KIII) activity, in microsomal fractions,
      while 100 nm Abeta25-35 inhibited PI3K activity in mitochondrial fractions. In
      plasma membrane-rich fractions, Abetas (> 0.5 nm) dose-dependently inhibited
      PI4KII activity, the maximal inhibition to 77-87% of control being reached around
      10 nm of Abetas without significant changes in apparent Km values for ATP and PI,
      suggesting non-competitive inhibition by Abetas. The inhibition by 10 nm Abeta25
      35 was reversible. In recombinant human PI4KIIalpha, inhibition profiles of
      Abetas were similar to those in rat brain plasma membranes. Therefore,
      pathophysiological concentrations of Abetas directly and reversibly inhibited
      plasma membrane PI4KII activity, suggesting that plasma membrane PI4KII is a
      target of Abetas in the pathogenesis of Alzheimer's disease.

PMID- 15569260
TI  - Modulation of cerebral vascular tone by activated glia: involvement of nitric
      oxide.
AB  - The ability of activated glia to affect cerebral vascular tone has been evaluated
      using an in vitro experimental system in which basilar arteries were incubated
      with glial cultures activated by treatment with lipopolysaccharide (LPS).
      Vascular tone was measured with an isometric myograph. Contraction in response to
      high KCl and serotonin was reduced in arteries co-incubated for 24 h with LPS
      activated glia, whereas the response to acetylcholine was not modified. The
      reduced contraction was prevented when the nitric oxide synthase (NOS) inhibitor
      L-N-nitro-arginine (L-NNA) was added throughout the whole incubation time
      (activation of glial cells with LPS + co-incubation of glial cells with cerebral
      arteries). Under these conditions, nitrite levels were drastically reduced. A
      reduced contraction to KCl was also observed after treatment of the cerebral
      vessel with sodium nitroprusside. In contrast, L-NNA added to the vessel did not
      modify the response to contracting stimuli and the expression of endothelial NOS
      was not modified in cerebral arteries pre-incubated with activated glia. These
      results suggest that activated glia, which finds an in vivo correlate in several
      neuropathological conditions, can contribute to changes of vascular tone by
      modifying the levels of nitric oxide (NO) to which the vessel is exposed.

PMID- 15569261
TI  - Regulation of A2B adenosine receptor functioning by tumour necrosis factor a in
      human astroglial cells.
AB  - Low-affinity A2B adenosine receptors (A2B ARs), which are expressed in
      astrocytes, are mainly activated during brain hypoxia and ischaemia, when large
      amounts of adenosine are released. Cytokines, which are also produced at high
      levels under these conditions, may regulate receptor responsiveness. In the
      present study, we detected A2B AR in human astrocytoma cells (ADF) by both
      immunoblotting and real-time PCR. Functional studies showed that the receptor
      stimulated adenylyl cyclase through Gs proteins. Moreover, A2B ARs were
      phosphorylated and desensitized following stimulation of the receptors with high
      agonist concentration. Tumour necrosis factor alpha (TNF-alpha) treatment (24- h)
      increased A2B AR functional response and receptor G protein coupling, without any
      changes in receptor protein and mRNA levels. TNF-alpha markedly reduced agonist
      dependent receptor phosphorylation on threonine residues and attenuated agonist
      mediated A2B ARs desensitization. In the presence of TNF-alpha, A2B AR
      stimulation in vitro induced the elongation of astrocytic processes, a typical
      morphological hallmark of in vivo reactive astrogliosis. This event was
      completely prevented by the selective A2B AR antagonist MRS 1706 and required the
      presence of TNF-alpha. These results suggest that, in ADF cells, TNF-alpha
      selectively modulates A2B AR coupling to G proteins and receptor functional
      response, providing new insights to clarify the pathophysiological role of A2B AR
      in response to brain damage.

PMID- 15569262
TI  - Identification of regulatory cis-acting elements for alternative splicing of
      presenilin 2 exon 5 under hypoxic stress conditions.
AB  - An alternatively spliced form of the presenilin 2 (PS2) gene lacking exon 5
      (PS2V) was found in human brains with sporadic Alzheimer's disease. PS2V was
      induced by hypoxic stress in human neuroblastoma SK-N-SH cells, indicating that
      hypoxic stress affects the splicing machineries for PS2 exon 5. Here, we
      identified the critical cis-acting element (sec 2) on the PS2 pre-mRNA
      responsible for the aberrant splicing of PS2 exon 5 under hypoxic stress
      conditions. The element was composed of 23 nucleotides in exon 5 and RNA
      structural analyses showed a stem-loop structure in this sequence. Treatment with
      an antisense oligonucleotide directed toward the cis-acting element caused an
      increase in exon 5 inclusion. These results indicate that the sec 2 identified in
      this study is a novel regulatory element for exon 5 splicing under stress
      conditions and that trans-acting factors could specifically bind to the element
      to skip exon 5 of PS2.

PMID- 15569263
TI  - Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced
      cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by
      modulating early growth response-1 transcription factor.
AB  - Epidemiological studies show reduced risk of Alzheimer's disease (AD) among
      patients using non-steroidal inflammatory drugs (NSAID) indicating the role of
      inflammation in AD. Studies have shown a chronic CNS inflammatory response
      associated with increased accumulation of amyloid peptide and activated microglia
      in AD. Our previous studies showed that interaction of Abeta1-40 or fibrilar
      Abeta1-42 caused activation of nuclear transcription factor, early growth
      response-1 (Egr-1), which resulted in increased expression of cytokines (TNF
      alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in monocytes. We
      determined whether curcumin, a natural product known to have anti-inflammatory
      properties, suppressed Egr-1 activation and concomitant expression of
      cytochemokines. We show that curcumin (12.5-25 microm) suppresses the activation
      of Egr-1 DNA-binding activity in THP-1 monocytic cells. Curcumin abrogated Abeta1
      40-induced expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP
      1beta, MCP-1 and IL-8) in both peripheral blood monocytes and THP-1 cells. We
      found that curcumin inhibited Abeta1-40-induced MAP kinase activation and the
      phosphorylation of ERK-1/2 and its downstream target Elk-1. We observed that
      curcumin inhibited Abeta1-40-induced expression of CCR5 but not of CCR2b in THP-1
      cells. This involved abrogation of Egr-1 DNA binding in the promoter of CCR5 by
      curcumin as determined by: (i) electrophoretic mobility shift assay, (ii)
      transfection studies with truncated CCR5 gene promoter constructs, and (iii)
      chromatin immunoprecipitation analysis. Finally, curcumin inhibited chemotaxis of
      THP-1 monocytes in response to chemoattractant. The inhibition of Egr-1 by
      curcumin may represent a potential therapeutic approach to ameliorate the
      inflammation and progression of AD.

PMID- 15569264
TI  - Proteasome inhibition increases DNA and RNA oxidation in astrocyte and neuron
      cultures.
AB  - Increased levels of nucleic acid oxidation have been described as part of normal
      brain aging and have been demonstrated to occur in multiple neurological
      disorders. The basis for increased nucleic acid oxidation in each of these
      conditions is presently unknown. Proteasome inhibition occurs in a host of
      neurodegenerative conditions and likely contributes to increased levels of
      oxidative damage and neurotoxicity. In the present study we demonstrate for the
      first time the ability of proteasome inhibition to increase the level of nucleic
      acid oxidation in primary neuron and astrocyte cultures. Administration of
      proteasome inhibitors (MG262, MG115) at concentrations that do not induce neuron
      death in the first 24 h of treatment, dramatically increase the levels of 8
      hydroxy-2'-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8OHG) immunoreactivity
      in both cell types. Neurons underwent larger increases in nucleic acid oxidation
      compared to astrocyte cultures. While both DNA and RNA oxidation were observed
      following proteasome inhibition, RNA appeared to undergo a greater degree of
      oxidation than DNA. Both 18S and 28S ribosomal RNA were dramatically decreased
      following proteasome inhibition. Interestingly, an accumulation of unprocessed
      and/or cross-linked RNA species was observed following proteasome inhibition.
      Taken together, these data indicate the ability of proteasome inhibition to
      increase the levels of nucleic acid oxidation in both neurons and astrocytes, and
      suggest that proteasome inhibition may have deleterious effects on transcription
      and translation in both neurons and glia.

PMID- 15569265
TI  - Minocycline prevents glutamate-induced apoptosis of cerebellar granule neurons by
      differential regulation of p38 and Akt pathways.
AB  - Minocycline has been shown to have remarkably neuroprotective qualities, but
      underlying mechanisms remain elusive. We reported here the robust neuroprotection
      by minocycline against glutamate-induced apoptosis through regulations of p38 and
      Akt pathways. Pre-treatment of cerebellar granule neurons (CGNs) with minocycline
      (10-100 microm) elicited a dose-dependent reduction of glutamate excitotoxicity
      and blocked glutamate-induced nuclear condensation and DNA fragmentations. Using
      patch-clamping and fluorescence Ca2+ imaging techniques, it was found that
      minocycline neither blocked NMDA receptors, nor reduced glutamate-caused rises in
      intracellular Ca2+. Instead, confirmed by immunoblots, minocycline in vivo and in
      vitro was shown to directly inhibit the activation of p38 caused by glutamate. A
      p38-specific inhibitor, SB203580, also attenuated glutamate excitotoxicity.
      Furthermore, the neuroprotective effects of minocycline were blocked by
      phosphatidylinositol 3-kinase (PI3-K) inhibitors LY294002 and wortmannin, while
      pharmacologic inhibition of glycogen synthase kinase 3beta (GSK3beta) attenuated
      glutamate-induced apoptosis. In addition, immunoblots revealed that minocycline
      reversed the suppression of phosphorylated Akt and GSK3beta caused by glutamate,
      as were abolished by PI3-K inhibitors. These results demonstrate that minocycline
      prevents glutamate-induced apoptosis in CGNs by directly inhibiting p38 activity
      and maintaining the activation of PI3-K/Akt pathway, which offers a novel
      modality as to how the drug exerts protective effects.

PMID- 15569266
TI  - Opposite regulation of the mitochondrial apoptotic pathway by C2-ceramide and
      PACAP through a MAP-kinase-dependent mechanism in cerebellar granule cells.
AB  - The sphingomyelin-derived messenger ceramides provoke neuronal apoptosis through
      caspase-3 activation, while the neuropeptide pituitary adenylate cyclase
      activating polypeptide (PACAP) promotes neuronal survival and inhibits caspase-3
      activity. However, the mechanisms leading to the opposite regulation of caspase-3
      by C2-ceramide and PACAP are currently unknown. Here, we show that PACAP prevents
      C2-ceramide-induced inhibition of mitochondrial potential and C2-ceramide-evoked
      cytochrome c release. C2-ceramide stimulated Bax expression, but had no effect on
      Bcl-2, while PACAP abrogated the action of C2-ceramide on Bax and stimulated Bcl
      2 expression. The effects of C2-ceramide and PACAP on Bax and Bcl-2 were blocked,
      respectively, by the JNK inhibitor L-JNKI1 and the MEK inhibitor U0126. L-JNKI1
      prevented the alteration of mitochondria induced by C2-ceramide while U0126
      suppressed the protective effect of PACAP against the deleterious action of C2
      ceramide on mitochondrial potential. Moreover, L-JNKI1 inhibited the stimulatory
      effect of C2-ceramide on caspase-9 and -3 and prevented C2-ceramide-induced cell
      death. U0126 blocked PACAP-induced Bcl-2 expression, abrogated the inhibitory
      effect of PACAP on ceramide-induced caspase-9 activity, and promoted granule cell
      death. The present study reveals that C2-ceramide and PACAP exert opposite
      effects on Bax and Bcl-2 through, respectively, JNK- and ERK-dependent
      mechanisms. These data indicate that the mitochondrial pathway plays a pivotal
      role in the pro- and anti-apoptotic effects of C2-ceramide and PACAP.

PMID- 15569267
TI  - Application of magnetically isolated rat retinal vascular endothelial cells for
      the determination of transporter gene expression levels at the inner blood
      retinal barrier.
AB  - The purpose of the present study was to quantify transporter gene levels at the
      inner blood-retinal barrier (inner BRB) using a combination of magnetic isolation
      method for rat retinal vascular endothelial cells (RVEC) and real-time
      quantitative PCR analysis. The transcript levels of CD31, Tie-2, claudin-5,
      occludin, Jam-1, mdr1a, oatp2, and oatp14 in the RVEC fraction were more than 100
      fold greater than those in the non-RVEC fraction, suggesting that these genes are
      predominantly expressed at the inner BRB. The transcript levels of GLUT1 and MCT1
      in the RVEC fraction were the most abundant in the respective transporter family,
      suggesting that GLUT1 and MCT1 play a predominant role in d-glucose and
      monocarboxylate transport, respectively, at the inner BRB. In conclusion,
      application of magnetically isolated RVEC is able to determine transporter gene
      levels at the inner BRB thereby increasing our understanding of inner BRB
      functions at a molecular level.

PMID- 15569268
TI  - Glucagon-like peptide: the time is near.

PMID- 15569269
TI  - Glucagon-like peptide-1: regulation of insulin secretion and therapeutic
      potential.
AB  - Glucagon-like peptide-1 (GLP-1) is an intestinally derived insulinotropic hormone
      currently under investigation for use as a novel therapeutic agent in the
      treatment of type 2 diabetes. One of several important effects of GLP-1 is on
      nutrient-induced pancreatic hormone release and is mediated by binding to a
      specific G-protein coupled receptor resulting in the activation of adenylate
      cyclase and an increase in cAMP generation. In the beta-cell, cAMP binds and
      modulates activities of both protein kinase A and cAMP-regulated guanine
      nucleotide exchange factor II, thereby enhancing glucose-dependent insulin
      secretion. The stimulatory action of GLP-1 on insulin secretion involves
      interaction with a plethora of signal transduction processes including ion
      channel activity, intracellular Ca(2+) handling and exocytosis of the insulin
      containing granules. In this review we focus principally on recent advances in
      our understanding on the cellular mechanisms proposed to underlie GLP-1's
      insulinotropic effect and attempt to incorporate this knowledge into a working
      model for the control of insulin secretion. Lastly, this review discusses the
      applicability of GLP-1 as a therapeutic agent for the treatment of type 2
      diabetes.

PMID- 15569270
TI  - A two-way cross-over bioequivalence study comparing two products of diclofenac
      sodium suppositories in healthy human volunteers.
AB  - This report presents the results of two treatment cross-over investigations on 20
      healthy male volunteers to assess the bioequivalence of two suppository products
      of diclofenac sodium. The study was carried out under US Food and Drug
      Administration Guidelines. The two products were voltaren (100 mg) suppository
      (Ciba-Giegy), as a reference product, and Inflaban (100 mg) suppository (The Arab
      Pharmaceutical Manufacturing Company, Ltd. "APM"), as a test product. Both
      products were administered rectally as a single dose (100 mg) separated by a one
      week wash-out period. Following drug administration, blood samples were collected
      over 12 hr, and serum harvested from the blood was analyzed for diclofenac sodium
      using a sensitive and specific high performance liquid chromatographic assay. The
      results of this investigation indicated that there were no statistically
      significant differences between the two products in either the mean concentration
      time profiles or in the obtained pharmacokinetic parameters, including area under
      the serum concentration-time curve for 12 hr (AUC(0-12h)), lag time between
      product administration and first appearance of the drug in serum (T(lag)), peak
      serum concentration (C(max)), and time to reach this peak serum concentration
      (T(max)). Concerning the relative extent of absorption, assessed by the AUC ratio
      (Inflaban/Voltaren) for 12 hr, the average value was found to be 1.00+/-0.09 with
      a 95% confidence limits (C.L.) of 0.82-1.18. Thus, these findings clearly
      indicate that the two products are bioequivalent in terms of rate and extent of
      drug absorption.

PMID- 15569271
TI  - Angiotensin II receptor mRNA expression and vasoconstriction in human coronary
      arteries: effects of heart failure and age.
AB  - Angiotensin II is a potent vasoconstrictor that is implicated in the pathogenesis
      of hypertension, heart failure and atherosclerosis. In the present study,
      angiotensin II receptor mRNA expression levels were quantified by real-time
      polymerase chain reaction and the vasocontractile responses to angiotensin II
      were characterised by in vitro pharmacology in endothelium-denuded human coronary
      arteries. Angiotensin II type 1 (AT(1)) and type 2 (AT(2)) receptor mRNA
      expression levels were significantly down-regulated in arteries from patients
      with heart failure as compared to controls. The angiotensin II-induced
      vasoconstriction diminished with increasing age in patients with heart failure
      (r(2)=0.31, P<0.05). Also, the AT(1) receptor mRNA expression levels decreased
      with increasing age in patients with heart failure (r(2)=0.74, P<0.05), while no
      such correlation could be shown in the control group (r(2)=0.04, P=n.s.). The
      AT(2) receptor mRNA expression levels did not correlate with age in patients with
      heart failure or controls. In conclusion, the diminished angiotensin II
      vasoconstriction with age in heart failure patients is most likely due to a lower
      density of AT(1) receptors and may result from a longer period of exposure to
      heart failure in older patients.

PMID- 15569272
TI  - Enzymatic oxidation of 2-phenylethylamine to phenylacetic acid and 2
      phenylethanol with special reference to the metabolism of its intermediate
      phenylacetaldehyde.
AB  - 2-phenylethylamine is an endogenous constituent of the human brain and is
      implicated in cerebral transmission. This bioactive amine is also present in
      certain foodstuffs such as chocolate, cheese and wine and may cause undesirable
      side effects in susceptible individuals. Metabolism of 2-phenylethylamine to
      phenylacetaldehyde is catalysed by monoamine oxidase B but the oxidation to its
      acid is usually ascribed to aldehyde dehydrogenase and the contribution of
      aldehyde oxidase and xanthine oxidase, if any, is ignored. The objective of this
      study was to elucidate the role of the molybdenum hydroxylases, aldehyde oxidase
      and xanthine oxidase, in the metabolism of phenylacetaldehyde derived from its
      parent biogenic amine. Treatments of 2-phenylethylamine with monoamine oxidase
      were carried out for the production of phenylacetaldehyde, as well as treatments
      of synthetic or enzymatic-generated phenylacetaldehyde with aldehyde oxidase,
      xanthine oxidase and aldehyde dehydrogenase. The results indicated that
      phenylacetaldehyde is metabolised mainly to phenylacetic acid with lower
      concentrations of 2-phenylethanol by all three oxidising enzymes. Aldehyde
      dehydrogenase was the predominant enzyme involved in phenylacetaldehyde oxidation
      and thus it has a major role in 2-phenylethylamine metabolism with aldehyde
      oxidase playing a less prominent role. Xanthine oxidase does not contribute to
      the oxidation of phenylacetaldehyde due to low amounts being present in guinea
      pig. Thus aldehyde dehydrogenase is not the only enzyme oxidising xenobiotic and
      endobiotic aldehydes and the role of aldehyde oxidase in such reactions should
      not be ignored.

PMID- 15569273
TI  - Transcriptional up-regulation in expression of 5-hydroxytryptamine2A and
      transcriptional down-regulation of angiotensin II type 1 receptors during organ
      culture of rat mesenteric artery.
AB  - The purpose of this study was to investigate in rat mesenteric artery if there is
      up-regulation of 5-hydroxytryptamine (5-HT) receptors and angiotensin II
      receptors and the potential role of protein kinase C activation in the smooth
      muscle cells during organ culture. Angiotensin II, 5-HT and potassium induced
      contraction of ring segments without endothelium, monitored by a sensitive in
      vitro pharmacology method. After the culture of the arterial ring segments for 24
      hr, the concentration-contraction curves induced by 5-HT slightly shifted towards
      to the left with pEC(50) from 6.64+/-0.11 to 6.84+/-0.11 and a significant
      increase in E(max) from 147+/-11% to 246+/-15% (P<0.05), compared with that
      obtained in fresh segments. In contrast, the angiotensin II concentration
      contraction curve only showed a significant decrease in E(max) from 99+/-10% to
      37+/-8%. Specific antagonists for the 5-HT type 2A receptors (5-HT(2A)) and
      angiotensin II type 1 receptors (AT(1)) demonstrated that the contractions
      occurred via 5-HT(2A) and AT(1) receptors, respectively. Real-time PCR revealed
      that the 5-HT(2A) receptor mRNA was up-regulated in parallel with the contractile
      response while there was a down-regulation of AT(1) receptor mRNA.
      Transcriptional inhibitor actinomycin D and specific protein kinase C inhibitor
      Ro31-8220 demonstrated that it was a transcriptional mechanism with involvement
      of protein kinase C that regulated the enhanced expression of 5-HT(2A) receptors
      in the mesenteric artery.

PMID- 15569274
TI  - Ca2+-dependent elevation of inositol 1,4,5-trisphosphate level induced by
      freezing or homogenization of tissues and cells.
AB  - Various cells and tissues contain high basal levels of inositol 1,4,5
      trisphosphate, raising questions about the functional significance of inositol
      1,4,5-trisphosphate in some tissues such as the heart. We used intact tissue and
      isolated cells from heart and liver of adult rats to examine if different
      fixation procedures might artificially elevate the level of inositol 1,4,5
      trisphosphate. The basal level of inositol 1,4,5-trisphosphate in intact, freeze
      clamped cardiac tissue from adult rats was 10 times higher than in isolated, non
      frozen cardiomyocytes, while freeze-clamped liver contained approximately 4 times
      higher inositol 1,4,5-trisphosphate levels than isolated, non-frozen hepatocytes.
      Stimulation with norepinephrine induced a significant increase in the inositol
      1,4,5-trisphosphate level in isolated cardiomyocytes, whereas no significant
      increase was observed in freeze-clamped cardiac tissue. Freezing of isolated
      cardiomyocytes or hepatocytes before extraction increased basal inositol 1,4,5
      trisphosphate levels 3 times. In cellular homogenates prepared in the presence of
      EGTA and stored at 4 degrees , readdition of calcium resulted in a time-dependent
      increase in inositol 1,4,5-trisphosphate mass and a decrease in the mass of
      phosphatidylinositol 4,5-bisphosphate (PIP(2)). The reaction was essentially
      complete within 30 sec. in homogenates from cardiomyocytes, while PIP(2)
      hydrolysis was slower in hepatocyte homogenates. Perfusion of intact rat hearts
      with EGTA present during the last 2 min. of perfusion, followed by freeze
      clamping, resulted in basal inositol 1,4,5-trisphosphate levels comparable to
      those in isolated cardiomyocytes, and norepinephrine stimulation increased
      inositol 1,4,5-trisphosphate mass by approximately 80%. The presence of EGTA did
      not significantly affect PIP(2) levels in perfused hearts. The results suggest
      that freezing or homogenization of intact tissue and isolated cells may result in
      Ca(2+)-dependent activation of phospholipase C, leading to high basal inositol
      1,4,5-trisphosphate levels that may mask agonist-induced changes.

PMID- 15569275
TI  - Transport and bioavailability studies of astragaloside IV, an active ingredient
      in Radix Astragali.
AB  - Astragaloside IV is an important constituent of Radix Astragali, a herbal remedy
      widely used in traditional Chinese medicine. Radix Astragali is administered
      orally but little is known about the transport properties and bioavailability of
      astragaloside IV. In this paper we report studies of the absorption of
      astragaloside IV in the perfused rat intestinal model, transport and uptake in
      Caco-2 cell monolayers and in vivo bioavailability in rat after an oral dose. In
      the perfused rat intestinal model, absorption of astragaloside IV was low from an
      aqueous solution but was significantly higher from a solution of Radix Astragali.
      Absorption was not affected by bile duct ligation. Transport through Caco-2 cells
      gave a very low permeability value (mean P(app) of 6.7+/-1.0 x 10(-8) cm/sec.)
      and uptake was unaffected by P-glycoprotein inhibitors. The absolute
      bioavailability of astragaloside IV in rat was 2.2%. The correlation between low
      permeability in vitro and poor bioavailability in vivo indicates in vitro
      absorption studies are useful in the evaluation of traditional Chinese medicines.

PMID- 15569276
TI  - Adenosine A1 receptor blockade mimics caffeine's attenuation of ethanol-induced
      motor incoordination.
AB  - The effects of co-administration of caffeine and ethanol were assessed on the
      motor coordination of rats on the accelerating rotarod (accelerod). Ethanol (2.5
      g/kg, orally) decreased motor performance on the accelerod. Co-administration of
      caffeine (5 and 20 mg/kg, orally) dose-dependently attenuated this ethanol
      induced deficit. Caffeine (20 mg/kg, orally) alone did not affect motor
      performance in the test. As caffeine is a non-selective adenosine receptor
      antagonist the ability of adenosine A(1) and A(2A) receptor blockade to attenuate
      ethanol-induced motor incoordination was determined. Pre-treatment with the
      adenosine A(1) receptor antagonist DPCPX (5 mg/kg, intraperitoneally) attenuated
      ethanol (2.5 g/kg, orally)-induced motor incoordination. By contrast, prior
      administration of the adenosine A(2A) selective antagonist SCH 58261 (10 mg/kg
      intraperitoneally) had no effect on the ethanol-induced motor deficit. These data
      demonstrate that adenosine A(1) receptor blockade mimics the inhibitory action of
      caffeine on ethanol-induced motor incorordination, and may contribute to the
      ability of caffeine to offset the acute intoxicating actions of ethanol.

PMID- 15569277
TI  - Abstracts of the 9th Congress of the Asian Pacific Society of Respirology.
      December 10-13, 2004. Hong Kong.

PMID- 15569278
TI  - Slow but steady progress in child health in Papua New Guinea.

PMID- 15569279
TI  - Prevention of neonatal group B streptococcal disease: progress, challenges and
      dilemmas.
AB  - Significant advances in the prevention of neonatal group B streptococcal (GBS)
      disease have occurred in the last decade. In Australia, as well as in centres
      overseas, intrapartum penicillin given to carrier mothers has been shown to
      unequivocally decrease early onset neonatal GBS sepsis. In choosing which women
      should receive intrapartum chemoprophylaxis, recent data suggest that screening
      programmes for the detection of GBS carriage may be more effective than risk
      based strategies to prevent early onset neonatal GBS sepsis. Combined vaginal and
      rectal swabs, collected between 35 and 37 weeks gestation, either by a health
      care worker or by the patient herself and inoculated onto selective media after
      enrichment provide the optimum conditions to detect carriage. Increasingly
      erythromycin and clindamycin resistance is being described overseas, which may
      influence the choice of antibiotics used in those allergic to penicillin.
      Widespread antibiotic use, particularly with broad-spectrum agents, may lead to
      increasing neonatal sepsis with ampicillin resistant organisms. Whilst rates of
      non-GBS neonatal sepsis are generally stable there is evidence suggesting that
      Escherichia coli sepsis in premature infants is increasing. Novel vaccination
      strategies for GBS are being developed that may ultimately provide broader
      protection for mothers and babies and eliminate the need for intrapartum
      antibiotics.

PMID- 15569280
TI  - ASCIA guidelines for prevention of food anaphylactic reactions in schools,
      preschools and child-care centres.
AB  - These guidelines have been developed by the anaphylaxis working party of the
      Australasian Society of Clinical Immunology and Allergy to provide advice for
      minimizing the risk of food-induced anaphylaxis in schools, preschools and child
      care centres. The guidelines outline four steps for the prevention of food
      anaphylactic reactions in children at risk and food policy measures specific to
      school age and preschool age children.

PMID- 15569281
TI  - Reducing the risks for food allergic children in schools and preschools.

PMID- 15569282
TI  - Randomized controlled trial of asthma education after discharge from an emergency
      department.
AB  - OBJECTIVES: To test the hypothesis that reinforcement of the advice given at the
      time of discharge from the emergency department by telephone consultation would
      improve asthma outcomes. METHODS: A randomized controlled trial of the parents of
      310 children who had been discharged from the emergency department with asthma
      was undertaken. The parents were randomized to receive either standard care (155
      children) or standard care plus education by telephone (155 children) from a
      trained asthma educator. Symptoms, parental asthma knowledge, parental quality of
      life and use of asthma action plans and preventer therapy were collected at
      baseline and 6 months later. The primary measure was days of wheeze in last 3
      months; intermediate measures were regular use of preventer medications,
      possession and use of written asthma action plan, parental asthma knowledge
      scores and parental quality of life scores. RESULTS: A total of 266 parents (136
      intervention) completed the follow-up questionnaires after 6 months. Both groups
      showed similar symptoms and process measures at baseline, apart from more regular
      use of preventer medication in the control children. At follow up, the
      intervention group children were significantly more likely than controls to
      possess (87.5% vs 72.3%; P = 0.002) a written asthma action plan. Possession of
      action plans increased from baseline in the intervention group but tended to
      decrease in the control group. Use of action plans was greater in the
      intervention group but decreased from baseline in both groups. Both intervention
      and control groups showed significant decreases in asthma symptoms. CONCLUSIONS:
      Reinforcement by telephone consultation did not improve the primary outcome of
      wheeze in the last 3 months. However, it increased the possession and regular use
      of written asthma action plans in the intervention group.

PMID- 15569283
TI  - Clonidine poisoning in children: a recent experience.
AB  - OBJECTIVES: To identify cases of clonidine poisoning presenting to a tertiary
      paediatric hospital and to investigate trends in presentation, outcome and
      prevention. Furthermore, any public health implications of the use of clonidine
      in children are to be explored. METHODS: Cases of clonidine poisoning presenting
      to Royal Children's Hospital were reviewed over the period from 1997 to 2001
      (inclusive), with significant data obtained from coded medical records. RESULTS:
      Twenty-four cases of clonidine poisoning were identified over the 5-year period.
      Nine patients ingested their own medication, which was prescribed for attention
      deficit hyperactivity disorder. Clonidine was prescribed for a child in 16 cases
      (67%). Impaired conscious state and bradycardia were the most common presenting
      features. Activated charcoal was given in 14 cases and volume expansion in six.
      There were 12 children (50%) who required admission to intensive care for
      monitoring, including three who received mechanical ventilation. The average
      length of stay was 25.7 h with no long-term complications. CONCLUSIONS: This is
      the largest series of clonidine poisoning in children recorded in Australia, with
      morbidity considerable. Emphasis needs to be placed on educating parents of
      clonidine's dangers in overdose to their own children as well as others.

PMID- 15569284
TI  - Use of complementary and alternative medicines by children and adolescents with
      inflammatory bowel disease.
AB  - OBJECTIVES: The use of complementary and alternative medicines (CAM) appears
      increasingly prevalent in children and adolescents. Individuals with chronic
      illness may have patterns of greater usage. This questionnaire-based study aimed
      to ascertain the frequency of use by a group of children with proven inflammatory
      bowel disease (IBD) and to consider the reasons for their use. METHODS: A
      questionnaire was sent by mail to the parents of patients currently attending a
      paediatric IBD clinic. Parents were asked to describe their child's usage of
      alternative and probiotic therapies and to comment on a number of aspects of such
      therapies. RESULTS: Forty-six (77%) of 60 mailed questionnaires were returned.
      The mean age of the children was 10.9 (+/- 4.1) years and they were taking an
      average of 1.7 (+/- 0.8) prescribed medications. Thirty-three (72%) of the
      children were said by their parents to be having CAM, with four having five or
      more such therapies (average 2.4 +/- 1.3 agents per child). The most commonly
      used agents were probiotics (78%) and fish oils (56%). A minority (12%) of
      respondents reported that their child's CAM was very effective, although many
      (50%) noted partial benefits. The 13 children who had never used any CAM
      therapies ('non-users') did not differ from the 'users' in terms of gender, age,
      disease or duration of disease. As expected, non-users expressed greater concerns
      about use of CAM and described different attitudes towards such therapies.
      CONCLUSION: Complementary and alternative medicines, especially probiotic
      therapies, frequently are administered to children and adolescents with
      inflammatory bowel disease. Often this appears to be due to parental frustration
      with managing their child's chronic illness. Practitioners caring for children
      and adolescents with IBD need to be aware that their patients may be using
      alternative therapies and adopt an open attitude in this situation.

PMID- 15569285
TI  - Paediatric resuscitation by phone: the call back.
AB  - OBJECTIVE: To assess whether the nationwide introduction of standardized
      paediatric resuscitation training has resulted in an increase in resuscitation
      knowledge from 1995 and whether this increase in knowledge is greater in those
      who have attended a resuscitation training course within the last year. METHODS:
      National telephone survey of paediatric residents. RESULTS: A total of 128 out of
      a possible 140 residents responded. The mean score in 2002 was significantly
      higher than in 1995. Those 2002 respondents who had attended a course scored
      significantly higher than both 1995 respondents, and those 2002 respondents who
      had not attended a course. There was no significant difference between those 2002
      respondents who had not attended a course and the 1995 respondents. CONCLUSION:
      There has been a significant increase in resuscitation knowledge from 1995 to
      2002. This improvement has occurred over a period coinciding with the nationwide
      introduction of standardized resuscitation training. The authors suggest that
      this improvement is, in part, due to the introduction of standardized paediatric
      resuscitation training.

PMID- 15569286
TI  - Effect of an early intervention programme on low birthweight infants with
      cerebral injuries.
AB  - OBJECTIVE: To determine the effect of an early intervention programme (EIP) on
      low birthweight infants with cerebral injuries. METHODS: Subjects were 23 high
      risk low birthweight infants (periventricular leukomalacia 15, intraventricular
      haemorrhage 5, both 3) receiving care in the neonatal intensive care unit (NICU)
      at Nagasaki University Hospital. Subjects were randomly assigned to the EIP group
      (n = 12) or the control group (n = 11). Participants in the EIP group received a
      Neonatal Behavioral Assessment scale (NBAS)-based intervention combined with
      developmental support designed to enhance the infants' development and the
      quality of the parent-infant relationship. The control group received routine
      medical nursing care without the EIP. The EIP began prior to discharge from the
      NICU and lasted until 6 months of corrected age. All children were examined on
      the NBAS preintervention and again at 44 weeks postconceptional age. Maternal
      anxiety status (STAI) and maternal feelings of confidence in dealing with her
      baby (LCC) were measured pre and postintervention. Mental and motor development
      was assessed postintervention using the Bayley Scale of Infant Development.
      RESULTS: Orientation and State Regulation of infant behavioural profiles, the
      STAI and LCC scores significantly improved in the EIP group (mean difference (95%
      CI): Orientation 0.7 (0.4, 1.1), State Regulation 0.9 (0.3, 1.5), STAI -5.5 (-
      9.1, -1.9, LCC 5.3 (4.2, 6.5)), but not in the control group. Bayley mental
      developmental index (MDI) score in the EIP group was higher than in the control
      group, but there was no significant difference between the two groups (mean
      difference (95% CI): MDI 8.5 (- 0.8, 17.8), PDI 6.7 (- 1.9, 15.4)). CONCLUSION:
      The EIP has beneficial effects on neonatal neurobehavioural development and
      maternal mental health of low birthweight infants with cerebral injuries. This
      evidence suggests that short-term changes in maternal mental health and infant
      neurobehaviour promoted by an EIP may serve to initiate a positive interaction
      between parents and infants.

PMID- 15569287
TI  - Childhood autism spectrum disorder in the Barwon region: a community based study.
AB  - OBJECTIVE: To establish a community database for children with autism spectrum
      disorder (ASD) to determine prevalence and identify subgroups based on key
      intellectual, clinical and family parameters. METHODS: Data were collected for
      children previously diagnosed with an ASD in the Barwon region using parental
      interview and review of the child's paediatric and psychological records.
      Preschool diagnoses were typically made by specialist psychologists and school
      age diagnoses made by a multidisciplinary team. RESULTS: One hundred and seventy
      seven children in the Barwon region were identified as having ASD (82% response
      rate). The prevalence of ASD was one per 255 children aged two to 17 years. The
      prevalence increased 10 fold over a 16-year period and this increase was
      relatively even across all levels of child intellectual functioning. Forty-two
      percent of children were intellectually disabled (IQ < 70) and performance IQ was
      significantly higher than verbal IQ but typical block design-comprehension
      subtest patterns were not common. Nine sibling pair families were identified, 24%
      were labelled as having attention deficit hyperactivity disorder (ADHD), 6% had
      epilepsy, and 18.3% were macrocephalic where data were available. Family
      difficulty was associated with the degree of obsessions/rituals, frequency and
      intensity of anger/aggression, and ADHD but overall was not associated with the
      child's intellectual status. CONCLUSIONS: The relatively rapid increase in
      prevalence is consistent with overseas studies and suggests significant changes
      in diagnostic criteria, increasing community awareness and the need for support
      at all levels of intellectual functioning. Increased occurrence in siblings and
      relatives gives further evidence for a genetic cause.

PMID- 15569288
TI  - Dr James George Beaney (1828-1891): a pioneer Australian paediatrician and
      paediatric surgeon.
AB  - Dr James George Beaney (1828-1891) was a flamboyant and controversial Melbourne
      surgeon and paediatrician. He was the first in Australia, in 1859, to publish a
      medical textbook; and the first, in 1873, to publish a paediatric text, Children:
      their treatment in health and disease. An analysis of four of his published works
      relating to paediatrics and paediatric surgery establishes his place as a true
      pioneer in the chronology of children's medicine and welfare in his adopted land.
      He undertook heroic yet conservative surgery on children, was the first to write
      in detail about paediatric anaesthesia, and was the pioneer of family planning in
      Australia. In Children: their treatment in health and disease, he described in
      detail the supreme importance of breastfeeding, detailed clear practical concepts
      for the weaning of infants and discussed the diagnosis and management of diseases
      of the mouth, ears, eyes and teeth of infants. Beaney was shunned by much of the
      established medical profession because of his self-promoting flamboyance and his
      egotism. However, an audit of surviving archives and of his published works
      affords him a place as another, hitherto unacknowledged true pioneer of
      Australian paediatrics.

PMID- 15569289
TI  - Seizures and a hiccup in the diagnosis.

PMID- 15569290
TI  - Maternal water intoxication as a cause of neonatal seizures.
AB  - A term infant was admitted at 6 h of age with seizures related to hyponatraemia.
      During the last hours of labour the infant's mother had drunk 3 L of water. After
      delivery the serum sodium was 121 mmol/L in the mother and 126 mmol/L in the
      infant. Both resolved spontaneously. We discuss this case and the impact of
      maternal fluid intake during labour on the fetus and neonate. Women should be
      advised that excessive oral fluid intake during labour could adversely affect
      both mother and infant.

PMID- 15569291
TI  - Uncommon complication of herpes simplex encephalitis.
AB  - A 9-year-old-girl who had herpes simplex encephalitis developed impending uncal
      herniation requiring surgical decompression. This case highlights the development
      of an uncommon complication despite the early initiation of treatment with
      acyclovir.

PMID- 15569292
TI  - 'Cerebral palsy' due to mitochondrial cytopathy.
AB  - Two children aged 10 and 13 years with initially static motor problems, diagnosed
      as cerebral palsy, were found to have respiratory chain defects after developing
      a progressive course and multisystem involvement. Mitochondrial cytopathies
      should be considered in the differential diagnosis of cerebral palsy.

PMID- 15569293
TI  - Difficulties in making the diagnosis of Hirschsprung disease in early infancy.
AB  - This study highlights the less common presentations of Hirschsprung disease (HD)
      and HD-associated enterocolitis (HAE) in neonates and infants. We present three
      infants whose diagnosis was delayed because of atypical presenting features,
      especially with failure to gain weight, decreased appetite, episodes of diarrhoea
      and vomiting and hypoalbuminaemia. The reported incidence of HAE ranges from 0 to
      16.2%. To avoid complications of life-threatening HAE, primary care physicians
      require a high index of suspicion of the more unusual presentations of HD in
      neonates and infants.

PMID- 15569294
TI  - Prevalence of overweight and obesity in Victorian 4-year-olds, 2002-4.

PMID- 15569295
TI  - Treating cystic fibrosis with fish oil.

PMID- 15569296
TI  - Response to 'Nutrition in cerebral palsy'.

PMID- 15569297
TI  - Re: Status dystonicus and Hallervorden-Spatz disease.

PMID- 15569300
TI  - From secondary to primary prevention of progressive renal disease: the case for
      screening for albuminuria.
AB  - Many subjects nowadays present with end-stage renal failure and its attendant
      cardiovascular complications without known prior renal damage. In this report we
      review the evidence available to strongly suggest that the present practice of
      secondary prevention in those with known prior renal disease should be extended
      to primary prevention for those subjects in the general population who are at
      risk for progressive renal failure, but who had never suffered from a primary
      renal disease. We show that such subjects can be detected by screening for
      albuminuria. Elevated urinary albumin loss is an indicator not only of poor
      renal, but also of poor cardiovascular prognosis. In addition to diabetic
      subjects who are at risk for albuminuria, we also show that hypertensive, obese,
      and smoking subjects are more susceptible. We suggest that therapies that have
      been shown to lower albumin excretion, such as ACE inhibitors, angiotensin II
      receptor antagonists, and statins be started early in such patients to prevent
      them from developing clinical renal disease and its attendant cardiovascular
      complications.

PMID- 15569301
TI  - Retinoids in nephrology: promises and pitfalls.
AB  - BACKGROUND: Retinoids, a family of vitamin A metabolites or analogs, play an
      important role in regulating cell proliferation, differentiation, and apoptosis.
      METHODS: The biological importance of retinoids in the kidney and the potential
      of retinoids in the treatment of renal diseases are reviewed. RESULTS: Vitamin A
      deficiency and mutations of retinoid nuclear receptors cause abnormalities in
      fetal kidneys, which might predispose to adult diseases such as hypertension.
      Further, the therapeutic value of retinoids in animal models of kidney diseases,
      such as lupus nephritis, puromycin aminonucleoside nephrosis, anti-glomerular
      basement membrane nephritis, mesangioproliferative nephritis, and acute renal
      allograft rejection has been unveiled recently. Retinoids target mesangial cells,
      podocytes, tubular epithelial cells, interstitial fibroblasts, as well as
      lymphocytes and macrophages. The anti-inflammation, anti-coagulation effects, and
      the proliferation- and immunity-modulating actions of retinoids, have been widely
      appreciated. Our recent in vitro data revealed a direct antifibrotic effect and a
      cytoprotective effect of retinoids in various renal cell types. In animal
      studies, the adverse effects of retinoids are generally minimal; however, the
      clinical use of retinoids in other diseases points to some major side effects. In
      addition, in vitro, retinoids can induce lipid accumulation in smooth muscle
      cells and macrophages and increase expression of some proinflammatory molecules,
      indicating that their clinical toxicity profile in the setting of renal diseases
      needs to be better understood. CONCLUSION: Retinoids not only are important in
      renal development, but also show promise as a new generation of renal medication
      and deserve to be tested in clinical trials to clarify their full potential.

PMID- 15569302
TI  - Comparison between siblings and twins supports a role for modifier genes in
      ADPKD.
AB  - BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized
      by intrafamilial variability in renal disease progression, which could result
      from a combination of environmental and genetic factors. Although a role for
      modifier genes has been evidenced in mouse models, direct evidence in ADPKD
      patients is lacking. The analysis of variability in affected siblings and
      monozygotic (MZ) twins would help evaluate the relative contribution of
      environment and genetic factors on renal disease progression in ADPKD. METHODS:
      The difference in the age at end-stage renal disease (ESRD) and the intraclass
      correlation coefficient (ICC) were quantified in a large series of ADPKD siblings
      from western Europe and compared with the values obtained in a series of MZ ADPKD
      twins from the same geographic area. RESULTS: Fifty-six sibships (including 129
      patients) and nine pairs of MZ twins were included. The difference in the age at
      ESRD was significantly higher in siblings (6.9 +/- 6.0 years, range 2 months to
      23 years) than in MZ twins (2.1 +/- 1.9 years, range 1 month to 6 years; P =
      0.02). Furthermore, the intraclass correlation coefficient was significantly
      lower in siblings than in MZ twins (0.49 vs. 0.92, respectively; P = 0.003). The
      intrafamilial difference in the age at ESRD was not influenced by gender.
      CONCLUSION: These data substantiate the existence of a large intrafamilial
      variability in renal disease progression in ADPKD siblings. The fact that the
      variability in siblings is in a significant excess of that found in MZ twins
      strongly suggests that modifier genes account for a significant part of this
      variability.

PMID- 15569303
TI  - AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type I
      receptor interaction.
AB  - BACKGROUND: The renin-angiotensin system (RAS) and the accumulation of advanced
      glycation end products (AGEs) have been implicated in the pathogenesis of
      diabetic nephropathy. Whether there is a functional interaction between the RAS
      and AGEs in diabetic nephropathy is not known. In this study, we investigated
      whether AGEs could activate autocrine angiotensin II (Ang II) signaling and
      subsequently induce transforming growth factor-beta (TGF-beta)-Smad signaling in
      cultured rat mesangial cells. METHODS: The intracellular formation of reactive
      oxygen species (ROS) was detected using the fluorescent probe CM-H2DCFDA. Ang II
      was measured by radioimmunoassay. TGF-beta released into media was quantitatively
      analyzed in an enzyme-linked immunosorbent assay (ELISA). Smad2, p27(Kip1) (p27),
      fibronectin, and receptor for AGEs (RAGE) protein expression were determined by
      Western blot analysis. TGF-beta-inducible promoter activity was analyzed by a
      luciferase assay. DNA synthesis was evaluated by 5-bomo-2'-deoxyuridine (BrdU)
      incorporation and de novo protein synthesis was determined by [3H]leucine
      incorporation. RESULTS: AGEs increased intracellular ROS generation in mesangial
      cells, and this effect was significantly inhibited by an antiserum against RAGE.
      AGEs also were found to stimulate Ang II production in a time- and dose-dependent
      manner, which was completely prevented by an antioxidant, N-acetylcysteine (NAC).
      AGE-induced TGF-beta overproduction was completely blocked by candesartan, an Ang
      II type 1 receptor (AT1R) antagonist. Both candesartan and neutralizing antibody
      against TGF-beta completely prevented AGEs-induced Smad2 phosphorylation and TGF
      beta-inducible promoter activity. Furthermore, AGEs were found to inhibit DNA
      synthesis and to stimulate de novo protein synthesis and fibronectin production
      in association with up-regulation of p27. All of these phenomena were completely
      prevented by candesartan or a polyclonal antibody against TGF-beta. CONCLUSION:
      The present study suggests that AGE-RAGE-mediated ROS generation activates TGF
      beta-Smad signaling and subsequently induces mesangial cell hypertrophy and
      fibronectin synthesis by autocrine production of Ang II. This pathway may provide
      an important link between metabolic and haemodynamic factors in promoting the
      development and progression of diabetic nephropathy.

PMID- 15569304
TI  - Estradiol reverses renal injury in Alb/TGF-beta1 transgenic mice.
AB  - BACKGROUND: Men with chronic renal disease progress more rapidly to renal failure
      than do women. Tranforming growth factor-beta (TGF-beta) plays a central role in
      promoting progressive renal injury, in part due to transcriptional effects
      mediated by cooperation between Smad proteins and the transcription factor Sp1.
      Estrogen negatively regulates Sp1 activity and reverses the stimulatory effects
      of TGF-beta on type IV collagen synthesis and cellular apoptosis in cultured
      mesangial cells. We hypothesized that the ability of estradiol to reverse the
      effects of TGF-beta underlies gender dimorphism in the progression of chronic
      renal disease. METHODS: We studied Alb/TGF-beta transgenic mice, which
      overexpress TGF-beta1 and develop proteinuria and progressive glomerulosclerosis.
      We implanted a sustained-release estradiol pellet or a placebo pellet into
      control and Alb/TGF-beta transgenic mice at 2 weeks of age. Animals were
      sacrificed at 5 weeks, at which time urine, blood, and renal tissue were obtained
      for study. RESULTS: The sustained-release estradiol pellet achieved a physiologic
      concentration of estradiol. TGF-beta levels were higher in estradiol-treated mice
      compared to placebo-treated mice. Proteinuria was reduced in estradiol-treated
      Alb/TGF-beta mice compared to placebo-treated transgenic mice. Mesangial
      expansion and closure of capillary loops with enhanced glomerular deposition of
      type I collagen, type IV collagen, and tissue inhibitor of metalloproteinase
      (TIMP-2) was observed in glomeruli of placebo-treated transgenic mice. Estrogen
      therapy reversed these abnormalities. CONCLUSION: Administration of estradiol to
      Alb/TGF-beta transgenic mice, which overexpress TGF-beta, ameliorated progressive
      renal injury. The ability of estradiol to reverse the pro-fibrotic effects of TGF
      beta, both in vitro and in vivo, may underlie the sexual dimorphism in renal
      disease progression observed in humans.

PMID- 15569305
TI  - High calcium diet down-regulates kidney angiotensin-converting enzyme in
      experimental renal failure.
AB  - BACKGROUND: Calcium salts are used as phosphate binders in renal failure, while
      high calcium diet also improves vasorelaxation and enhances natriuresis. The
      influences of calcium intake on renal renin-angiotensin system (RAS) are largely
      unknown. METHODS: Four weeks after NTX, rats were put on 3.0% or 0.3% calcium
      diet for 8 weeks (12-week study). In additional experiments, 15 weeks after NTX,
      rats were put on similar diets for 12 weeks (27-week study). Appropriate blood,
      urine, and kidney samples were taken. Renal angiotensin-converting enzyme (ACE)
      and angiotensin II receptors (AT1, AT2) were examined using autoradiography, ACE
      also using Western blotting, and connective tissue growth factor (CTGF) using
      immunohistochemistry. RESULTS: In the 12-week study, albuminuria increased 5-fold
      in NTX rats, but only 2-fold in calcium NTX rats on 3.0% calcium. In the 27-week
      study, high calcium intake decreased blood pressure, retarded progression of
      renal failure, reduced glomerulosclerosis, interstitial damage, and aortic
      calcifications, and improved survival from 50% to 92% in NTX rats. In both
      experiments plasma parathyroid hormone and phosphate were elevated after NTX, and
      suppressed by high calcium diet, while kidney ACE was down-regulated by 40% or
      more after increased calcium intake. In the 27-week study renal CTGF was
      decreased and cortical AT1 receptor density reduced after high calcium diet.
      CONCLUSION: High calcium diet down-regulated kidney ACE, reduced albuminuria and
      blood pressure, and favorably influenced kidney morphology in experimental renal
      failure. These findings suggest a link between calcium metabolism and kidney ACE
      expression, which may play a role in the progression of renal damage.

PMID- 15569306
TI  - D1 dopamine receptor signaling involves caveolin-2 in HEK-293 cells.
AB  - BACKGROUND: Dopamine receptors in the kidney, especially those belonging to the
      D1-like receptor family, are important in the regulation of renal function and
      blood pressure. Because of increasing evidence that G protein-coupled receptors
      (GPCRs) are associated with caveolae and lipid rafts, we tested the hypothesis
      that the D1 dopamine receptor (D1R) and signaling molecules are regulated by
      caveolin in caveolae or lipid rafts. METHODS: Six experimental approaches were
      used: (1) construction of tagged human D1Rs (hD1Rs) and transfectants; (2) cell
      culture [human embryonic kidney (HEK)-293 and immortalized rat renal proximal
      tubule cells] and biotinylation; (3) cell fractionation by sucrose gradient
      centrifugation; (4) immunoprecipitation and immunoblotting; (5)
      immunofluorescence and confocal microscopy; and (6) adenylyl cyclase assays.
      RESULTS: hD1Rs, heterologously expressed in HEK-293 cells, formed protein species
      with molecular mass ranging from 50 to 250 kD, and were localized in lipid rafts
      and nonraft plasma membranes. The hD1Rs cofractionated with caveolin-2, G protein
      subunits, and several signaling molecules. Both exogenously expressed hD1Rs and
      endogenously expressed rat D1Rs colocalized and coimmunoprecipitated with
      caveolin-2. A D1R agonist (fenoldopam) increased the amount of caveolin-2beta
      associated with hD1Rs and activated adenylyl cyclase to a greater extent in lipid
      rafts than in nonraft plasma membranes. Reduction in the expression of caveolin-2
      with antisense oligonucleotides attenuated the stimulatory effect of fenoldopam
      on cyclic adenosine monophosphate (cAMP) accumulation. CONCLUSION: The majority
      of hD1Rs are distributed in lipid rafts. Heterologously and endogenously
      expressed D1Rs in renal cells are associated with and regulated by caveolin-2.

PMID- 15569307
TI  - Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: impact on
      proliferation and apoptosis.
AB  - BACKGROUND: The intrarenal renin-angiotensin system (RAS) is intimately involved
      in the tubular cell proliferation, apoptosis and regeneration that occur
      following renal injury. Though tubular angiotensin II (Ang II) type 2 receptors
      (AT2R) decrease greatly after birth, their number increases after injury.
      Notably, during recovery from injury, renal tubular cells display a relatively
      immature phenotype expressing genes that are involved in nephron development, for
      example, the paired homeobox-2 gene (Pax-2). The present investigation
      hypothesized that AT2R activation would stimulate Pax-2 gene expression in
      immortalized rat renal proximal tubular cells (IRPTC), as we have found in fetal
      cells. METHODS: Pax-2 gene expression in IRPTC was evaluated by
      immunofluorescence, Western blot, reverse transcription-polymerase chain reaction
      (RT-PCR) with or without Ang II treatment; apoptosis and proliferation were
      analyzed by terminal transferase-mediated deoxyuridine triphosphate (dUTP) nick
      end-labeling (TUNEL) assay and bromodeoxyuridine (BrdU) incorporation in stable
      IRPTC transformants with Pax-2 sense and antisense orientation, respectively.
      RESULTS: Ang II up-regulated Pax-2 gene expression via AT2R in IRPTC. The
      stimulatory effect of both Ang II on Pax-2 gene expression was blocked by
      PD123319 (AT2R inhibitor), AG 490 (specific Janus kinase 2 (JAK2) inhibitor) and
      genistein (tyrosine kinase inhibitor), but not by losartan (AT1R inhibitor).
      Stable transfection of sense Pax-2 cDNA increased, whereas antisense Pax-2 cDNA
      down-regulated Pax-2 expression. CONCLUSION: Our studies suggest that Ang II
      stimulates Pax-2 gene expression in IRPTC via AT2R and the JAK2/signal
      transducers and activators of transcription (STAT) signaling transduction
      pathway, which may be important in renal repair following injury. Cells lacking
      Pax-2 gene expression appear to be prone toward apoptosis rather than
      proliferation.

PMID- 15569308
TI  - Isolation and characterization of conditionally immortalized mouse glomerular
      endothelial cell lines.
AB  - BACKGROUND: The culture and establishment of glomerular cell lines has proven to
      be an important tool for the understanding of glomerular cell functions in
      glomerular physiology and pathology. Especially, the recent establishment of a
      conditionally immortalized visceral epithelial cell line has greatly boosted the
      research on podocyte biology. METHODS: Glomeruli were isolated from H-2Kb-tsA58
      transgenic mice that contain a gene encoding a temperature-sensitive variant of
      the SV40 large tumor antigen, facilitating proliferative growth at 33 degrees C
      and differentiation at 37 degrees C. Glomerular endothelial cells were isolated
      from glomerular outgrowth by magnetic beads loaded with CD31, CD105, GSL I-B4,
      and ULEX. Clonal cell lines were characterized by immunofluorescence staining
      with antibodies/lectins specific for markers of endothelial cells, podocytes, and
      mesangial cells. Putative glomerular endothelial cell lines were analyzed for (1)
      cytokine-induced expression of adhesion molecules; (2) tube formation on Matrigel
      coating; and (3) the presence of fenestrae. RESULTS: As judged by immunostaining
      for Wilms tumor-1, smooth muscle actin (SMA), podocalyxin, and von Willebrand
      factor (vWF), we obtained putative endothelial, podocyte and mesangial cell
      lines. The mouse glomerular endothelial cell clone #1 (mGEnC-1) was positive for
      vWF, podocalyxin, CD31, CD105, VE-cadherin, GSL I-B4, and ULEX, internalized
      acetylated-low-density lipoprotein (LDL), and showed increased expression of
      adhesion molecules after activation with proinflammatory cytokines. Furthermore,
      mGEnC-1 formed tubes and contained nondiaphragmed fenestrae. CONCLUSION: The
      mGEnC-1 represents a conditionally immortalized cell line with various
      characteristics of differentiated glomerular endothelial cells when cultured at
      37 degrees C. Most important, mGEnC-1 contains nondiaphragmed fenestrae, which is
      a unique feature of glomerular endothelial cells.

PMID- 15569309
TI  - Caspase-1-deficient mice are protected against cisplatin-induced apoptosis and
      acute tubular necrosis.
AB  - BACKGROUND: Cisplatin is a commonly used chemotherapeutic agent which causes
      apoptosis or necrosis of renal tubular epithelial cells in vitro. Caspases are a
      family of cysteine proteases that mediate apoptosis (caspase-3) and inflammation
      (caspase-1). Although well studied in vitro, caspases have not been previously
      studied in cisplatin-induced acute renal failure (ARF) in vivo. METHODS:
      Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type and caspase-1
      deficient (-/-) C57BL/6 mice. Serum creatinine and blood urea nitrogen (BUN), and
      renal caspase-1, -3, -8 and -9 activity were measured on days 1, 2, and 3 after
      cisplatin injection. Kidneys were examined for acute tubular necrosis (ATN),
      neutrophils, and apoptosis on days 1, 2, and 3. RESULTS: After cisplatin
      injection, serum creatinine and BUN were normal on day 1, began to increase on
      day 2, and peaked on day 3. Similarly, ATN scores and neutrophil counts peaked on
      day 3. In contrast, renal apoptosis significantly increased on day 2. Renal
      dysfunction, apoptosis, ATN scores and neutrophil infiltration were all reduced
      in the caspase-1(-/-) mice. In wild-type mice, caspase-1 and -3 activity
      increased on days 2 and 3. Caspase-3 activity was reduced by approximately 50% in
      caspase-1(-/-) mice; active caspase-3 detected by immunoblot was also reduced in
      caspase-1(-/-) mice. In vitro, addition of recombinant caspases to kidney
      cytosolic extracts determined that caspase-1 activates caspase-3 in renal tissue.
      CONCLUSION: These results indicate that caspase-1 contributes to cisplatin
      induced ARF and ATN (day 3). Furthermore, caspase-1 affects caspase-3 activation
      and apoptosis in cisplatin-induced ARF (day 2).

PMID- 15569310
TI  - The characterization of a specific Thy-1 molecular epitope expressed on rat
      mesangial cells.
AB  - BACKGROUND: An Experimental model of proliferative glomerulonephritis induced by
      an antibody against Thy-1 antigen has been established. However, the
      pathophysiologic role and the critical epitope of Thy-1 molecule for induction of
      mesangial cell dysfunction remain unknown. We have reported that monoclonal
      antibody 1-22-3 recognizes specific epitope which could transduce highly
      effective activation in mesangial cells. Identification of functional domains on
      cell surfaces is indispensable for understanding the molecular mechanisms of
      mesangial cell function. This study was undertaken to determine the functional
      domain containing the specific epitope recognized by monoclonal antibody 1-22-3.
      METHODS: A series of glutathione-S-transferase (GST)-truncated-Thy-1 proteins
      were generated using pGEX 4T-1 vector. COS cells were transiently transfected
      with plasmid vectors which could express the rat Thy-1 and mutant-Thy-1. RESULTS:
      Western blot analysis using recombinant GST-truncated-Thy-1 revealed that 1-22-3
      bound to epitope at amino acids 15-23 (LRLDCRHEN). Enzyme-linked immunosorbent
      assay (ELISA) revealed that synthetic LRLDCRHEN peptides could inhibit the
      binding of 1-22-3 to rat mesangial cells and GST-Thy-1 protein. Using peptides as
      antigens, ELISA showed that 1-22-3 bound to the LRLDCRHEN but not to the
      RVNLFSDRF, which was corresponding to at amino acids 59-67 of rat Thy-1. 1-22-3
      could bind the COS cells which express rat Thy-1 proteins, but could not bind rat
      truncated-Thy-1 which lacks residues 15-23. CONCLUSION: Critical epitope detected
      by 1-22-3 in this study may play an important role in mesangial function and
      injury.

PMID- 15569311
TI  - Expression and activity of soluble guanylate cyclase in injury and repair of anti
      thy1 glomerulonephritis.
AB  - BACKGROUND: Activation of soluble guanylate cyclase and generation of cyclic
      3',5'-guanosine monophosphate (cGMP) is the main signal transducing event of the
      L-arginine-nitric oxide pathway. The present study analyzes the expression and
      activity of the nitric oxide-cGMP signaling cascade in and the effect of the
      specific soluble guanylate cyclase stimulator Bay 41-2272 on the early injury and
      subsequent repair phase of acute anti-thy1 glomerulonephritis. METHODS: Anti-thy1
      glomerulonephritis was induced by OX-7 antibody injection in rats. In protocol 1
      (injury), Bay 41-2272 was given starting 6 days before antibody injection. One
      day after disease induction, parameters of mesangial cell injury (glomerular cell
      number and inducible nitric oxide synthesis) were analyzed. In protocol 2
      (repair), Bay 41-2272 treatment was started one day after antibody injection. On
      day 7, parameters of glomerular repair [glomerular matrix score, expression of
      transforming growth factor (TGF)-beta1, fibronectin, and plasminogen-activator
      inhibitor (PAI)-1, infiltration with macrophages and fibrinogen deposition
      (indicating platelet localization)] were determined. In both protocols, tail
      bleeding time, systolic blood pressure, plasma cGMP levels, glomerular mRNA
      expression of endothelial nitric oxide synthase (eNOS), alpha1 and beta1 soluble
      guanylate cyclase, and basal and nitric oxide-stimulated glomerular cGMP
      production were analyzed. RESULTS: Bay 41-2272 prolonged bleeding time, reduced
      blood pressure, and increased plasma cGMP levels in both protocols. In the injury
      experiment, disease induction increased inducible nitric oxide synthesis and
      reduced glomerular cell number, while expression and activity of soluble
      guanylate cyclase was almost completely diminished. Bay 41-2272 did not affect
      parameters of mesangial cell injury and glomerular soluble guanylate cyclase
      expression and activity. In the repair protocol, expression and activity of
      soluble guanylate cyclase was markedly increased by disease. Bay 41-2272 further
      enhanced soluble guanylate cyclase expression and activity. This went along with
      significant reductions in proteinuria, glomerular matrix accumulation, expression
      of TGF-beta1, fibronectin, and PAI-1, macrophage infiltration and fibrinogen
      deposition as compared to the untreated anti-thy1 animals. CONCLUSION: Glomerular
      nitric oxide signaling via cGMP is markedly impaired during injury of anti-thy1
      glomerulonephritis, while it is highly up-regulated during subsequent repair.
      Further pharmacologic soluble guanylate cyclase stimulation limits glomerular TGF
      beta overexpression and matrix expansion, suggesting that the soluble guanylate
      cyclase enzyme represents an important antifibrotic pathway in glomerular
      disease.

PMID- 15569312
TI  - Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function,
      and bone in rats with renal failure.
AB  - BACKGROUND: Hyperphosphatemia and disturbances in calcium or parathyroid hormone
      (PTH) metabolism contribute to the high incidence of cardiovascular disease and
      renal osteodystrophy in chronic renal failure (CRF). We evaluated the effect of
      hyperphosphatemia on the cardiovascular system, on renal function, and on bone in
      experimental uremia. METHODS: Wistar rats were submitted to parathyroidectomy
      (PTx) and 5/6 nephrectomy (Nx) with minipump implantation, delivering 1-34 rat
      PTH (physiologic rate), or were sham-operated and received vehicle. Only
      phosphorus content (low-phosphorus (LP) 0.2%; high-phosphorus (HP) 1.2%)
      differentiated diets. We divided the groups as follows: PTx +Nx +LP; sham + LP;
      PTx + Nx + HP; and sham + HP. Tail-cuff pressure and weight were measured weekly.
      After 2 months, biochemical, arterial, and myocardial histology and bone
      histomorphometry were analyzed. RESULTS: Heart weight normalized to body weight
      (heart weight/100 g body weight) was higher in PTx + Nx + HP rats (PTx + Nx + HP
      = 0.36 +/- 0.01 vs. sham + HP = 0.29 +/- 0.01, PTx + Nx + LP = 0.32 +/- 0.01,
      sham + LP = 0.28 +/- 0.01) (P < 0.05). Serum creatinine levels were higher in PTx
      + Nx + HP rats than in PTx + Nx + LP rats (1.09 +/- 0.13 vs. 0.59 +/- 0.03 mg/dL)
      (P < 0.05). Levels of PTH did not differ significantly between the groups.
      Myocardial and arterial histology detected no vascular calcification or fibrosis.
      Bone histomorphometry revealed an association, unrelated to uremia, between HP
      diets and decreased trabecular connectivity. CONCLUSION: Myocardial hypertrophy,
      impaired renal function, and adverse effects on bone remodeling were associated
      with hyperphosphatemia and were not corrected by PTH replacement. Although no
      vascular calcification was observed in this model, we cannot rule out an adverse
      effect of hyperphosphatemia on the vascular bed. Our finding underscores the
      importance of phosphorus control in reducing morbidity and mortality in CRF
      patients.

PMID- 15569313
TI  - Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in
      collecting duct cells.
AB  - BACKGROUND: Urinary concentrating defects and polyuria are the most important
      renal manifestations of hypercalcemia and the resulting hypercalciuria. In this
      study, we tested the hypothesis that hypercalciuria-associated polyuria in kidney
      collecting duct occurs through an impairment of the vasopressin-dependent
      aquaporin 2 (AQP2) water channel targeting to the apical membrane possibly
      involving calcium-sensing receptor (CaR) signaling. METHODS: AQP2-transfected
      collecting duct CD8 cells were used as experimental model. Quantitation of cell
      surface AQP2 immunoreactivity was performed using an antibody recognizing the
      extracellular AQP2 C loop. Intracellular cyclic adenosine monophosphate (cAMP)
      accumulation was measured in CD8 cells using a cAMP enzyme immunoassay kit. To
      study the translocation of protein kinase C (PKC), membranes or cytosol fractions
      from CD8 cells were subjected to Western blotting using anti-PKC isozymes
      antibodies. The amount of F-actin was determined by spectrofluorometric
      techniques. Intracellular calcium measurements were performed by
      spectrofluorometric analysis with Fura-2/AM. RESULTS: We demonstrated that
      extracellular calcium (Ca2+ o) (5 mmol/L) strongly inhibited forskolin-stimulated
      increase in AQP2 expression in the apical plasma membrane. At least three
      intracellular pathways activated by extracellular calcium were found to
      contribute to this effect. Firstly, the increase in cAMP levels in response to
      forskolin stimulation was drastically reduced in cells pretreated with Ca2+ o
      compared to untreated cells. Second, Ca2+ o activated PKC, known to counteract
      vasopressin response. Third, quantification of F-actin demonstrated that Ca2+ o
      caused a nearly twofold increase in F-actin content compared with basal
      conditions. All these effects were mimicked by a nonmembrane permeable agonist of
      the extracellular CaR, Gd3+. CONCLUSION: Together, these data demonstrate that
      extracellular calcium, possibly acting through the endogenous CaR, antagonizes
      forskolin-induced AQP2 translocation to the apical plasma membrane in CD8 cells.
      In hypercalciuria, this mechanism might blunt water reabsorption and prevent
      further calcium concentration, thus protecting against a potential risk of
      urinary calcium-containing stone formation.

PMID- 15569314
TI  - Binding of the chemokine SLC/CCL21 to its receptor CCR7 increases adhesive
      properties of human mesangial cells.
AB  - BACKGROUND: Adherence of human mesangial cells to the surrounding matrix
      contributes to glomerular homeostasis and is important for the maintenance of
      glomerular architecture and function in normal adult human kidney. The expression
      of chemokines and corresponding chemokine receptors on adjacent intrinsic renal
      cells indicates a novel chemokine/chemokine receptor function on nonimmune cells
      important for glomerular homeostasis. A constitutive expression of the chemokine
      SLC/CCL21 on human podocytes and of its corresponding receptor CCR7 on mesangial
      cells was shown before. SLC/CCL21 has a positive effect on proliferation and
      migration of mesangial cells and leads to increased cell survival in Fas-induced
      apoptosis. In leukocytes chemokines mediate integrin-dependent firm adhesion.
      Therefore, we examined the influence of chemokine receptor CCR7 activation by
      SLC/CCL21 on adhesive properties of human mesangial cells to matrix molecules.
      METHODS: Adhesion assays, mechanical detachment assays, and evaluation of
      integrin activation by integrin-linked kinase activity were performed. Changes in
      the cytoskeletal F-actin were illustrated by phalloidin immunofluorescence
      staining. RESULTS: SLC/CCL21 stimulation enhanced adhesiveness to fibronectin in
      a time- and concentration-dependent manner. SLC/CCL21 also increased the firmness
      of mesangial cells adhesion as judged by detachment assays. Furthermore
      activation of integrin-linked kinase occurred with SLC/CCL21 addition to
      mesangial cells, resulting in increased phosphorylation of glycogen synthase
      kinase-3 (GSK-3) and protein kinase B (PKB/Akt). Exposure of mesangial cells to
      SLC/CCL21 also resulted in F-actin rearrangements with membrane ruffling and
      extensions leading to bridging between mesangial cells. CONCLUSION: Activation of
      CCR7 on mesangial cells by SLC/CCL21 enhances the degree and firmness of cell
      adhesion and increases cell spreading and the formation of cell-cell contacts.
      This includes integrin-linked kinase activation and F-actin rearrangements. Thus,
      local chemokine generation and chemokine receptor expression on mesangial cells
      may play an important role in the maintenance of glomerular homeostasis and in
      local remodeling processes.

PMID- 15569315
TI  - CCR1 blockade reduces interstitial inflammation and fibrosis in mice with
      glomerulosclerosis and nephrotic syndrome.
AB  - BACKGROUND: CC chemokines mediate leukocyte infiltration into inflamed tissue. We
      have recently shown that blockade of the CC chemokine receptor CCR1 reduces
      interstitial inflammation and fibrosis in murine obstructive nephropathy.
      However, it is not known whether CCR 1 blockade is protective in progressive
      renal injury associated with severe proteinuria. We therefore studied the effect
      of the small-molecule CCR1 antagonist BX471 in a murine model of adriamycin
      induced focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome and
      progressive interstitial inflammation and fibrosis. METHODS: Adriamycin
      nephropathy with persistent proteinuria was induced in male BALB/c mice by two
      intravenous injections of adriamycin (13 mg/kg) at day 0 and 14. BX471 treatment
      was started at day 14 when proteinuria and interstitial inflammation had
      developed. At 6 weeks, renal histology was studied by morphometry and
      immunohistochemistry. RESULTS: At week 6, adriamycin-treated mice showed FSGS,
      associated with tubulointerstitial injury consisting of tubular dilation and
      atrophy, interstitial leukocyte infiltration, and fibrosis. The mRNA expression
      of CCR1 and CC chemokines, including the CCR1 ligands CCL3 (MIP-1alpha) and CCL5
      (RANTES), was up-regulated in diseased kidneys, with a prominent interstitial
      expression of CCL5. Compared to vehicle-treated controls BX471 significantly
      reduced the amount of macrophages and T lymphocytes in interstitial lesions by
      51% and 22%, respectively. Markers of renal fibrosis such as interstitial
      fibroblasts (48%) and interstitial volume (23%) were significantly reduced by
      BX471 treatment. In contrast, the extent of proteinuria and glomerular sclerosis
      was not affected by BX471 treatment. CONCLUSION: Blockade of CCR1 substantially
      reduced interstitial leukocyte accumulation and the subsequent renal fibrosis in
      a murine model of nephrotic syndrome and FSGS. These findings support a role for
      CCR1 in interstitial leukocyte recruitment and suggest that CCR1 blockade might
      be a new therapeutic strategy in progressive nephropathies such as FSGS.

PMID- 15569316
TI  - Fluorescent imaging of acute mercuric chloride exposure on cultured human kidney
      tubular epithelial cells.
AB  - BACKGROUND: Imaging of intracellular mercuric ion is necessary for mechanism of
      renal toxicity of exposure to HgCl2. The distribution of Hg2+ inside a living
      cell, however, is still invisible due to the lack of high selective and sensitive
      fluorescent molecular probe for Hg2+. METHODS: A new fluorescent probe, EPNP, was
      applied to the cultured cells of human kidney proximal tubular epithelial cell
      line (HKC) in the presence of HgCl2 and some other bivalent ions. The relative
      fluorescence intensity of EPNP was measured and fluorescence images were taken by
      laser scanning confocal microscope. RESULTS: Results showed it led to an Hg2+
      concentration- and time-dependent increase in fluorescence intensity, and
      responded weakly for some other heavy and transition metal ions. It could be seen
      during acute exposure on HKC cells, Hg2+ locate perinuclear, and on nuclear
      membrane, which was beyond what one knew before. CONCLUSION: EPNP is a real-time
      and on-line probe for imaging Hg2+ in a living cell due to its high selectivity
      and sensitivity for Hg2+ and slow bleaching/fading. Both the probe and the new
      results about the distribution of intracellular Hg2+ may be helpful for relevant
      biologic research.

PMID- 15569317
TI  - A carboxy-terminus motif of HKalpha2 is necessary for assembly and function.
AB  - BACKGROUND: The present experiments were designed to study the importance of the
      carboxy-terminus of HKalpha2, for both function and integrity of assembly with
      beta1-Na+,K+-ATPase. METHODS: For this purpose, stop codons were created, by
      polymerase chain reaction (PCR), at different positions in the carboxy-terminus
      of HKalpha2. Subsequently, chimeras between HKalpha2 and the carboxy-terminus of
      alpha1-Na+,K+-ATPase or with the carboxy-terminus of the gastric H+,K+-ATPase
      were created. Human embryonic kidney HEK-293 cells were used as expression
      systems for functional studies using 86Rb+ uptake and alpha/beta assembly using
      specific antibodies. RESULTS: The results demonstrate that the entire carboxy
      terminus of HKalpha2 is required for optimal protection of the alpha/beta complex
      from degradation and for functionality as evidenced by 86Rb+ uptake. The results
      also demonstrate that there was flexibility in the sequence of the carboxy
      terminus. The last two tyrosines (Y1035Y1036) of HKalpha2 could be mutated to
      alanines and the carboxy-terminus of HKalpha2 could be replaced by the carboxy
      terminus of alpha1-Na+,K+-ATPase while preserving transport activity. CONCLUSION:
      The entire carboxy-terminus of HKalpha2 is required for stable assembly with
      beta1-Na+,K+-ATPase and functionality.

PMID- 15569318
TI  - Elevated extracellular calcium levels induce smooth muscle cell matrix
      mineralization in vitro.
AB  - BACKGROUND: Hyperphosphatemia, elevated calcium x phosphorus product (Ca x P),
      and calcium burden, major causes of vascular calcification, are correlated with
      increased cardiovascular morbidity and mortality in dialysis patients. METHODS:
      To address the underlying mechanisms responsible for these findings, we have
      utilized an in vitro human smooth muscle cell (HSMC) model of vascular
      calcification. Previous studies using this system demonstrated enhanced
      calcification of HSMC cultures treated with phosphorus levels in the
      hyperphosphatemic range, and implicated a sodium-dependent phosphate cotransport
      dependent mechanism in this effect. In the present study, we examine the effect
      of increasing calcium concentrations on HSMC calcification in vitro. RESULTS:
      Increasing calcium to levels observed in hypercalcemic individuals increased
      mineralization of HSMC cultures under normal phosphorus conditions. Importantly,
      at these total calcium concentrations, ionized calcium levels increased from 1.2
      mmol/L to 1.7 mmol/L, consistent with levels observed physiologically in
      normocalcemic and hypercalcemic individuals, respectively. Furthermore,
      increasing both calcium and phosphorus levels led to accelerated and increased
      mineralization in the cultures. Calcium-induced mineralization was dependent on
      the function of a sodium-dependent phosphate cotransporter, since it was
      inhibited by phosphonoformic acid (PFA). While elevated calcium did not affect
      short-term phosphorus transport kinetics, long-term elevated calcium treatment of
      HSMCs induced expression of the sodium-dependent phosphate cotransporter, Pit-1.
      CONCLUSION: These studies suggest that elevated calcium may stimulate HSMC
      mineralization by elevating Ca x P product and enhancing the sodium-dependent
      phosphate cotransporter-dependent mineralization pathway previously observed in
      HSMCs.

PMID- 15569319
TI  - Overexpression of HSP-72 confers cytoprotection in experimental peritoneal
      dialysis.
AB  - BACKGROUND: Peritoneal dialysis is complicated by mesothelial cell injury due to
      low biocompatibility of peritoneal dialysis fluid (PDF). We have previously
      demonstrated that heat shock protein (HSP)-72 is potently up-regulated in
      response to PDF exposure of mesothelial cells in in vitro and in vivo models of
      peritoneal dialysis. The aim of this study was to evaluate potential
      cytoprotective effects of overexpression of HSP-72. METHODS: Cytoprotection was
      assessed by comparing cellular viability between pretreated versus nonpretreated
      human mesothelial cells (Met 5a; ATCC, Manassas, VA, USA, and primary cell
      cultures) subjected to extended, usually lethal PDF exposure times (120 min,
      CAPD2; Fresenius, Bad Homburg, Germany). Pretreatment was performed with exposure
      to PDF (60 min, CAPD2; Fresenius) or heat (15 min, 41.5 degrees C), and by
      transient transfection with HSP-72. RESULTS: When mesothelial cells were
      pretreated by nonlethal exposure to PDF or heat, HSP-72 was markedly up-regulated
      (>5-fold, P < 0.01). Pretreated human mesothelial cells were significantly
      protected against subsequent "lethal" exposures to PDF, as assessed by dye
      exclusion (>50% reduction, P < 0.05) and lactate dehydrogenase (LDH) release
      (>30% reduction, P < 0.05). Comparable cytoprotection (50% reduction by dye
      exclusion) was indicated by overexpression of HSP-72 in cultered human
      mesothelial cells (>5-fold) after transient transfection with HSP-72. This
      cytoprotection was confirmed at a cellular basis by double staining techniques
      with HSP-72 and ApopTag (apoptosis detection kit). CONCLUSION: Our study
      therefore shows that the mesothelial stress response confers cytoprotection in
      experimental peritoneal dialysis, mediated by the induction of HSP-72, and that
      the stimulus of the pretreatment does not have to be identical to the subsequent
      injury. These data offer the basis for an attractive novel therapeutic approach
      against PDF toxicity.

PMID- 15569320
TI  - Validation of internal control genes for gene expression analysis in diabetic
      glomerulosclerosis.
AB  - BACKGROUND: Gene expression analysis is an invaluable tool in the study of
      diabetic glomerulosclerosis. The necessary denominator for the quantitative
      expression of a specific gene is the expression level of a second gene that is
      presumed to remain unchanged. Thus, it is critical that the stability of this
      housekeeping gene in diabetic glomeruli or in cultured glomerular cells is not
      altered by the disease or a high glucose environment, respectively. Although gene
      expression quantification, achieved by Northern blot analysis or real-time
      reverse transcription-polymerase chain reaction (RT-PCR) has been extensively
      applied in diabetic renal tissue in vivo and in vitro, there are no studies
      validating the use of any specific endogenous control gene in these measurements.
      METHODS: We performed real-time RT-PCR using RNA from microdissected diabetic
      glomeruli and from mesangial cells cultured in high glucose concentration to
      investigate gene expression stability of beta-actin, glyceraldehyde-3-phosphate
      dehydrogenase (GADPH), phospholipase A2, beta2-microglobulin, acidic ribosomal
      protein 36B4, and cyclophilin A. RESULTS: Using an analysis method which is
      independent of gene abundance and compares the pair-wise variation of a given
      housekeeping gene with all other control genes, beta-actin and phospholipase A2,
      were found to be the most stable genes in diabetic glomeruli and in primary
      mesangial cells exposed to 20 mmol/L glucose. CONCLUSION: It is proposed that the
      expression level of these genes is the best reference to evaluate relative
      changes in gene activity in diabetic/high glucose exposed glomerular tissues.

PMID- 15569321
TI  - Increased methylglyoxal and advanced glycation end products in kidney from
      spontaneously hypertensive rats.
AB  - BACKGROUND: Methylglyoxal (MG), a metabolite of glucose, causes nonenzymatic
      glycation of proteins to form irreversible advanced glycation end products
      (AGEs). The role of MG in the development of essential hypertension is unknown,
      although MG has been extensively studied in relation to diabetes. METHODS: Blood
      pressure of spontaneously hypertensive rats (SHR) and paired Wistar Kyoto (WKY)
      rats was measured at 5, 8, 13, and 20 weeks of age. HPLC was used to determine
      the levels of plasma and kidney MG, as well as reduced or oxidized glutathione in
      the kidney. MG-induced AGEs, Nepsilon-carboxyethyl-lysine (CEL), and Nepsilon
      carboxymethyl-lysine (CML) in the kidney were detected by immunohistochemistry.
      Glutathione peroxidase and reductase activities in the kidney were also
      determined. RESULTS: Plasma MG levels were significantly elevated in SHR, but not
      in WKY rats, at 8, 13, and 20 weeks of age in parallel with blood pressure
      increase. Kidney MG levels in SHR were increased by 21% and 38% at 13 and 20
      weeks, respectively, compared to age-matched WKY rats. There were no differences
      in blood pressure and MG levels in plasma and kidney between SHR and WKY rats at
      5 weeks of age. Immunohistochemistry revealed more intense staining for CML and
      CEL in kidneys from SHR compared to WKY rats from 8 weeks onward. Most of the
      staining was localized to renal tubules with some staining in the glomerular
      vessels. CONCLUSION: MG and AGEs formation was significantly elevated in kidney
      from SHR, which may cause local vascular and tubular damage, contributing to the
      development and complications of hypertension.

PMID- 15569322
TI  - Evidence for compromised aldosterone synthase enzyme activity in preeclampsia.
AB  - BACKGROUND: In normal pregnancy, an increased aldosterone (Aldo) concentration
      coincides with volume expansion. In preeclampsia, Aldo levels are low despite
      intravascular volume depletion. The present investigation aimed to characterize
      the compromised Aldo synthesis in preeclampsia, and to identify the molecular
      basis hereof. METHODS: We recruited 66 pregnant women (24 uneventful, 42
      preeclamptic). Genomic DNA was isolated from peripheral blood leukocytes. Urine
      samples were obtained for gas chromatography-mass spectroscopic measurements of
      steroid hormones reflecting apparent Aldo synthase (CYP11B2) and 11-hydroxylase
      (CYP11B1) activities. Polymerase chain reaction (PCR)-based screening for CYP11B2
      mutations was performed by SSCP, restriction analysis, and sequencing. RESULTS:
      CYP11B1 activity was unaltered, but reduction of mean tetrahydro (TH)-Aldo
      excretion by a factor of 3.9 indicated a diminished CYP11B2 activity in
      preeclampsia. Accordingly, the ratios of (TH-11-dehydrocorticosterone [A]+TH
      corticosterone [B]+5alpha-THB) to (TH-cortisone +TH-cortisol [F]+5alpha-THF) and
      of 18-OH-THA to THAldo were increased in preeclampsia 2.6- and 15.2-fold,
      respectively, indicating reduced Aldo synthesis due to diminished methyl oxidase
      (MO) activity. A lower percentage of women with normal pregnancies had CYP11B2
      mutations when compared to preeclamptic women (P < 0.05). Eight polymorphisms
      were detected, two of which were non-amino acid conserving. Of those, the
      mutation V386A, earlier found to jeopardize MO activity, was exclusively observed
      in preeclampsia (0% vs. 17%; P < 0.05). CONCLUSION: Aldo deficiency due to a
      compromised MO step of Aldo synthesis favors extracellular volume depletion, and
      may account for an increased risk of placental hypoperfusion and consecutive
      development of preeclampsia. The sole presence of mutation V386A in preeclamptic
      mothers may identify a subgroup with an increased risk to develop preeclampsia
      during pregnancy.

PMID- 15569323
TI  - Lead exposure raises superoxide and hydrogen peroxide in human endothelial and
      vascular smooth muscle cells.
AB  - BACKGROUND: Chronic lead exposure causes hypertension and cardiovascular disease,
      which are associated with, and, in part, due to oxidative stress. While
      occurrence of oxidative stress in lead-exposed animals and cultured endothelial
      cells has been well-established, direct and specific evidence on the type of the
      reactive oxygen species (ROS) produced by lead-exposed vascular cells is lacking
      and was investigated. METHODS: Human coronary endothelial (EC) and vascular
      smooth muscle cells (VSMC) were incubated in appropriate culture media in the
      presence of either 1 ppm or 10 ppm lead acetate or sodium acetate (control) for 1
      to 30 minutes or 60 hours. Productions of superoxide and hydrogen peroxide in the
      cell populations were determined by flow cytometry using hydroethidine and
      dihydrorhodamine, respectively. Data from a minimum of 10,000 cells were
      collected and analyzed using Cell Quest software. In addition, Cu Zn superoxide
      dismutase (SOD), catalase, glutathione peroxidase (GPX), and NAD(P)H oxidase
      (gp91phox) were measured. RESULTS: Short-term lead exposure resulted in a
      significant rise in both superoxide and hydrogen peroxide production by both EC
      and VSMC. After long-term exposure, detectable superoxide levels fell to near
      normal level, while hydrogen peroxide production remained high. This was
      associated with up-regulations of gp91phox, elevation of superoxide dismutase,
      reduction of VSMC catalase, and no change in GPX levels. Together, these events
      can account for the observed decline in superoxide and the rise in hydrogen
      peroxide following long-term lead exposure. CONCLUSION: Lead exposure promotes
      generation of superoxide and hydrogen peroxide in human EC and VSMC. This
      phenomenon can potentially contribute to the pathogenesis of the lead-associated
      hypertension and cardiovascular disease, and points to the potential benefit of
      lowering lead burden in the exposed populations.

PMID- 15569324
TI  - Endothelial dysfunction as a modifier of angiogenic response in Zucker diabetic
      fat rat: amelioration with Ebselen.
AB  - BACKGROUND: Progression of nephropathy in metabolic syndrome is associated with
      microvasculopathy and vascular dropout. METHODS: Eight- and 22-week-old Zucker
      diabetic fat (ZDF) and Zucker lean (ZL) rats were studied to characterize the
      progression of nephropathy, and to test the effect of a peroxynitrite scavenger,
      Ebselen, on renal microvasculature and angiogenic competence. RESULTS: Capillary
      density was increased, both in the cortex (P < 0.05) and in the inner medulla (P
      < 0.001) by the age of 8 weeks, but significantly decreased (P < 0.01 and P <
      0.001) by the age of 22 weeks in ZDF compared to ZL rats. Similarly, the
      angiogenic competence of cortical and medullary renal explants was increased in 8
      week-old ZDF (P < 0.01), but decreased at 22 weeks (P < 0.001). Alterations of
      angiogenic competence in ZDF rats were associated with altered expression of
      vascular endothelial growth factor (VEGF), reduced expression of Flk-1, and
      neuropilin. Acetylcholine-induced relaxation of microdissected interlobar
      arteries from 8-week-old ZDF rats was unimpaired, but significantly attenuated in
      22-week-old ZDF rats (P < 0.001). Treatment with Ebselen partially prevented the
      decrease in capillary density and angiogenic competence of renal explants, and
      restored acetylcholine-induced vasorelaxation in 22-week-old ZDF rats.
      CONCLUSION: The progression of nephropathy in ZDF rats is associated with
      decreased angiogenic competence both ex vivo and in vivo. This is accompanied by
      a altered expression of VEGF system components and endothelial dysfunction, and
      scavenging peroxynitrite with Ebselen ameliorates the progression of
      microvasculopathy and partially restores angiogenesis. These findings reveal the
      complex mechanism of microvascular dropout in experimental metabolic syndrome.

PMID- 15569325
TI  - Temporal adaptation of tubuloglomerular feedback: effects of COX-2.
AB  - BACKGROUND: Reductions in proximal reabsorption cause increases in delivery of
      sodium chloride to the macula densa (MD), which activates the tubuloglomerular
      feedback (TGF) mechanism and reduces glomerular filtration rate. TGF undergoes
      temporal adaptation, permitting filtration rate to rise in spite of elevated MD
      delivery of NaCl. Inhibitors of nitric oxide synthase I (NOS I) prevent TGF
      adaptation, but angiotensin-converting enzyme inhibitors have no effect. COX-2
      activity moves in parallel with changes in NOS I and intrarenal renin. We
      examined the impact of COX-2 inhibition on TGF temporal adaptation and effects of
      inhibition of COX-2 and NOS I on plasma and kidney angiotensin II (Ang II).
      METHODS: Kidney blood flow (RBF) and glomerular filtration rate (GFR) were
      measured before and during benzolamide (BNZ) infusion in control Wistar rats and
      rats concurrently receiving COX-2 inhibitors. Plasma and kidney angiotensin II
      content was evaluated by radioimmunoassay in control rats, rats after 60 minutes
      of BNZ, and during COX-2 and NOS-1 inhibition after BNZ. RESULTS: BNZ reduced
      both RBF and GFR in all groups. During BNZ, RBF and GFR returned to normal
      control values within 60 minutes. COX-2 inhibitors totally prevented TGF
      adaptation. Plasma and kidney Ang II did not change after BNZ, and NOS I and COX
      2 inhibitors had no effect on plasma or intrarenal Ang II. CONCLUSION: Within 1
      hour after BNZ, rats undergo TGF temporal adaptation. Administration of COX-2
      inhibitors prevented TGF temporal adaptation, identical to the effect of NOS I
      inhibition. Changes in intrarenal Ang II cannot explain this prevention of TGF
      temporal adaptation.

PMID- 15569326
TI  - Impaired monocyte cytokine production in critically ill patients with acute renal
      failure.
AB  - BACKGROUND: Plasma levels of pro- and anti-inflammatory cytokines are predictive
      of mortality in patients with acute renal failure (ARF). Anti-inflammatory
      strategies are postulated to be beneficial in treatment. However, there are few
      studies simultaneously examining monocyte cytokine production and plasma cytokine
      levels in patients with ARF. METHODS: Study populations consisted of 20
      critically ill patients with ARF, 19 critically ill patients without ARF (CRIT
      ILL), 28 healthy subjects (HS), 19 patients with chronic kidney disease (CKD),
      and 15 patients with end-stage renal disease (ESRD). Monocyte intracellular
      content of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8, and
      tumor necrosis factor-alpha (TNF-alpha) was determined by flow cytometry in whole
      blood. Plasma interleukin 6 and TNF-alpha concentrations were determined by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: At baseline, there were no
      differences in intracellular monocyte cytokine levels between groups. After
      lipopolysaccaride stimulation, monocyte production of IL-1beta, TNF-alpha, and IL
      6 in ARF patients was reduced by 41%, 84%, and 45%, respectively, compared to
      healthy subjects (P < 0.01 in each case), and similarly reduced compared to CKD
      and ESRD patients, and were similar to CRIT ILL patients. Plasma IL-6 levels were
      significantly higher in ARF patients than healthy subjects, CKD, and ESRD
      patients (all P < 0.001). CONCLUSION: Critically ill patients with acute renal
      failure have impaired monocyte cytokine production and elevated plasma cytokine
      levels in a pattern that closely resembles critically ill patients without ARF,
      and that is dissimilar to CKD and ESRD patients.

PMID- 15569327
TI  - Validation of the Kidney Disease Quality of Life (KDQOL) cognitive function
      subscale.
AB  - BACKGROUND: Formal cognitive function testing is cumbersome, and no self
      administered instruments for estimating cognitive function in persons with
      chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been
      validated. The goal of this study was to determine the validity of the Kidney
      Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of
      cognitive impairment in persons with kidney disease. METHODS: We administered the
      KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross
      sectional study of cognitive function. Scores on the Modified Mini-Mental State
      Exam (3MS) were considered the gold standard measure of global cognitive
      function. Performance characteristics of the KDQOL-CF were assessed using
      correlation coefficients, Bland-Altman plots, and receiver operating
      characteristic curves. RESULTS: Median scores on the KDQOL-CF were 73
      (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73
      100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly
      correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global
      cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF
      accurately classified 76% of subjects, with 52% sensitivity and 81% specificity.
      On multivariable analysis, cerebral and peripheral vascular disease,
      benzodiazepine use, and higher serum phosphorus concentrations were associated
      with lower KDQOL-CF scores, while beta blocker use, education, and higher serum
      albumin concentrations were associated with higher KDQOL-CF scores. CONCLUSION:
      The KDQOL-CF is a valid instrument for estimating cognitive function in patients
      with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected
      individuals may prove to be an effective and efficient strategy for identifying
      cognitive impairment in patients with kidney disease.

PMID- 15569328
TI  - Creatinine levels among Mexican Americans, Puerto Ricans, and Cuban Americans in
      the Hispanic Health and Nutrition Examination Survey.
AB  - BACKGROUND: Although Latinos constitute the largest and fastest growing minority
      group in the United States, little is known about the prevalence of renal disease
      among different Latino subgroups. METHODS: We used data from the Hispanic Health
      and Nutrition Examination Survey (HHANES) to compare serum creatinine
      measurements among Mexican Americans, mainland Puerto Ricans, and Cuban
      Americans. We compared estimated creatinine clearance across Latino subgroups
      adjusted for demographic, clinical, and socioeconomic characteristics (including
      known predictors of chronic kidney disease) using survey logistic regression
      analysis. RESULTS: Cuban Americans had higher mean serum creatinine levels than
      the other groups across both gender and age categories. In multivariable
      analysis, Puerto Ricans [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.16
      to 2.60] and Cuban Americans (OR 4.59, CI 2.53 to 8.31) were more likely than the
      referent category of Mexican Americans to have an estimated creatinine clearance
      < 60 mL/min/1.73 m2. CONCLUSION: Serum creatinine levels differ substantially
      among Latino subgroups, suggesting national origin needs to be taken into
      consideration in studies of renal disease in Latinos. In addition, our findings
      highlight the need for more contemporary studies directly comparing both
      incidence rates of end-stage renal disease and measured renal function among
      Latino subgroups, perhaps leading to subgroup-specific prediction equations.

PMID- 15569329
TI  - Predictive value of urinary micro-cholesterol (mCHO) levels in patients with
      progressive glomerular disease.
AB  - BACKGROUND: Trace amounts of lipids are present in the urine of patients with
      glomerular disease, raising the possibility that the excess lipids reabsorbed by
      tubule cells may be toxic to these cells. In the present study, we assessed the
      prognostic value of micro-cholesterol (mCHO) levels in patients with chronic
      glomerular disease. METHODS: The urinary mCHO levels of healthy subjects and
      patients with chronic kidney disease were measured by the enzymatic cholesterol
      cycling (ECC) method with a minimum detection level of 0.10 x 10(-3) mmol/L.
      First, the urinary mCHO levels of healthy subjects and 320 patients with various
      glomerular diseases with proteinuria >1000 mg/gCr were measured. Second,
      correlations of urinary mCHO levels with those of various other molecules,
      including albumin, IgG, IgM, transferrin, phospholipid, alpha1-microglobulin
      (alpha1MG), Apo A1, Apo A2, and Apo B, and urinary fatty body counts, were
      determined. Third, urinary mCHO, total protein (TP), albumin, and N-acetyl-beta-D
      glucosaminidase (NAG) levels were measured longitudinally over 12 months (20.5 +/
      5.8 months) in 68 nondiabetic patients with impaired renal function [serum
      creatinine (Cr) > or = 1.5 mg/dL]. Correlations of the concentrations of urinary
      parameters in the initial 3-month period with the slopes of the reciprocal of
      creatinine versus time for the entire follow-up period were assessed by the ROC
      method and multiple regression analysis. RESULTS: Urinary mCHO levels of the
      healthy subjects were 0.06 to 0.72 mg/gCr for males and 0.16 to 2.34 mg/gCr for
      females. Urinary mCHO levels in subjects with minimal change nephrotic syndrome
      were significantly lower than those in the patients with other glomerular
      diseases with massive proteinuria. Urinary mCHO levels correlated significantly
      with Apo A1 and Apo A2 levels, but not with urinary Apo B levels, in the latter
      subjects. The correlation coefficient of urinary fatty body counts (a marker of
      lipoprotein loading tubulopathy) with mCHO was higher than those with TP,
      albumin, IgG, IgM, and alpha1MG. The urinary mCHO elevation was significantly
      greater in patients who had a nonselective index of proteinuria than in those
      with a highly or moderately selective index. In nondiabetic patients with
      impaired renal function, the urinary mCHO level had a higher predictive value for
      rapid decline of renal function than TP, albumin, or NAG. CONCLUSION: The urinary
      cholesterol level corresponds to the magnitude of urinary HDL excretion, and
      correlates with the degree of lipoprotein loading tubulopathy. Measurement of
      urinary mCHO by the ECC method is a simple and useful tool for predicting
      progression of chronic glomerular disease.

PMID- 15569330
TI  - The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese.
AB  - BACKGROUND: A considerable diversity in prognosis is seen with lupus
      glomerulonephritis (LGN). Hence, the clinical usefulness of a recent
      International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003
      classification to judge the long-term outcome of human LGN has been investigated.
      METHODS: We studied retrospectively 60 subjects with LGN (7 males, 53 females,
      mean age of 33 years old) who underwent renal biopsies and were followed from 1
      to 366 months, with a mean of 187 months. We diagnosed renal pathology as
      classes, active and sclerosing lesions, according to the new and WHO1995
      classification of LGN, and analyzed the clinicopathologic factors affecting to
      the prognosis of LGN. RESULTS: New classification got much higher consensus in
      the judgment of classes (98% vs. 83%, P = 0.0084). The group of Class IV-S (N =
      6) or IV-G (N = 17) at initial biopsies showed higher rate of end-stage renal
      failure (ESRF) compared with that of Class I, II, III or V (40.9% vs. 2.6%, P <
      0.001). The mean 50% renal survival time of Class IV was 189 +/- 29 months, and
      patients with Class IV-S tended to have a poorer prognosis (95 +/- 22 months for
      IV-S vs. 214 +/- 35 months for IV-G, P = 0.1495). Class IV was also selected as
      the most significant risk factor for ESRF by stepwise model (P = 0.002). In
      subanalysis for ESRF in Class IV (-S or -G), treatment including
      methylprednisolone pulse therapy was only selected as a significant improving
      factor for primary outcome (P = 0.034). In addition, activity index was the
      significant risk factor of death and/or ESRF after initial renal biopsies (P =
      0.043). As for actuarial patient death during all follow-up periods,
      complications with anti-phospholipid syndrome or nephrotic syndrome were
      significant risk factors (P = 0.013, P = 0.041, respectively). CONCLUSION: New
      ISN/RPS 2003 classification provided beneficial pathologic information relevant
      to the long-term renal outcome and the optimal therapy preventing ESRF and/or
      death in patients with LGN.

PMID- 15569331
TI  - The differential impact of risk factors on mortality in hemodialysis and
      peritoneal dialysis.
AB  - BACKGROUND: While the survival ramifications of dialysis modality selection are
      still debated, it seems reasonable to postulate that outcome comparisons are not
      the same for all patients at all times. Trends in available data indicate the
      relative risk of death with hemodialysis (HD) compared to peritoneal dialysis
      (PD) varies by time on dialysis and the presence of various risk factors. This
      study was undertaken to identify key patient characteristics for which the risk
      of death differs by dialysis modality. METHODS: Analyses utilized incidence data
      from 398,940 United States Medicare patients initiating dialysis between 1995 and
      2000. Proportional hazards regression identified the presence of diabetes, age,
      and the presence of comorbidity as factors that significantly interact with
      treatment modality. Stratifying by these factors, proportional and
      nonproportional hazards models were used to estimate relative risks of death [RR
      (HD:PD)]. RESULTS: Of the 398,940 patients studied, 11.6% used PD as initial
      therapy, 45% had diabetes mellitus (DM), 51% were 65 years or older, and 55% had
      at least one comorbidity. Among the 178,693 (45%) patients with no baseline
      comorbidity, adjusted mortality rates in nondiabetic (non-DM) patients were
      significantly higher on HD than on PD [age 18-44: RR (95% CI) = 1.24 (1.07,
      1.44); age 45-64: RR = 1.13 (1.02, 1.25); age 65+: RR = 1.13 (1.05, 1.21)]. Among
      diabetic (DM) patients with no comorbidity, HD was associated with a higher risk
      of death among younger patients [age 18-44: RR = 1.22(1.05, 1.42)] and a lower
      risk of death among older patients [age 45-64: RR = 0.92 (0.85, 1.00); age 65+:
      RR = 0.86 (0.79, 0.93)]. Within the group of 220,247 (55%) patients with baseline
      comorbidity, adjusted mortality rates were not different between HD and PD among
      non-DM patients [age 18-44: RR = 1.19 (0.94, 1.50); age 45-64: RR = 1.01 (0.92,
      1.11); age 65+: RR = 0.96 (0.91, 1.01)] and younger DM patients [age 18-44: RR =
      1.10 (0.92, 1.32)], but were lower with HD among older DM patients with baseline
      comorbidity [age 45-64: RR = 0.82 (0.77, 0.87); age 65+: RR = 0.80 (0.76, 0.85)].
      CONCLUSION: Valid mortality comparisons between HD and PD require patient
      stratification according to major risk factors known to interact with treatment
      modality. Survival differences between HD and PD are not constant, but vary
      substantially according to the underlying cause of ESRD, age, and level of
      baseline comorbidity. These results may help identify technical advances that
      will improve outcomes of patients on dialysis.

PMID- 15569332
TI  - The effect of fruits and vegetables on urinary stone risk factors.
AB  - BACKGROUND: The overall effect of fruit and vegetable intake on urinary stone
      risk profile is not yet known. METHODS: We studied the effect of a two-week
      period of fruit and vegetable elimination on urinary stone risk profile in 12
      normal adults, and of supplementing the diet with a fair quantity of low-oxalate
      fruits and vegetables in 26 idiopathic calcium stone formers characterized by
      hypocitraturia and a very low fruit and vegetable intake in their usual diet.
      RESULTS: In the normal subjects, the elimination of fruits and vegetables from
      the diet decreased the urinary excretion of potassium (-62%), magnesium (-26%),
      citrate (-44%) and oxalate (-31%), and increased that of calcium (+49%) and
      ammonium (+12%) (P < 0.05 for all). The relative saturation for calcium oxalate
      and calcium phosphate increased from 6.33 to 8.24 (P = 0.028), and from 0.68 to
      1.58 (P = 0.050), respectively. In the hypocitraturic stone formers, the
      introduction of these foods in the diet increased urinary volume (+64%), pH (from
      5.84 to 6.19), excretion of potassium (+68%), magnesium (+23%), and citrate
      (+68%), while it decreased the excretion of ammonium (-18%) (P < 0.05 for all).
      The relative saturation for calcium oxalate and uric acid fell from 10.17 to 4.96
      (P < 0.001), and from 2.78 to 1.12 (P = 0.003), respectively. CONCLUSION: The
      total elimination of fruits and vegetables in normal subjects brings about
      adverse changes in the urinary stone risk profile that are only partially
      counterbalanced by a reduction in oxalate. In contrast, the addition of these
      foods to the diet of hypocitraturic stone formers not used to eating them not
      only significantly increases citrate excretion without affecting oxalate
      excretion, but also decreases calcium oxalate and uric acid relative saturation.

PMID- 15569333
TI  - Mycophenolate therapy of SLE membranous nephropathy.
AB  - BACKGROUND: The immunosuppressant mycophenolic acid (MMF) has been used
      successfully to manage proliferative forms of systemic lupus erythematosus (SLE)
      glomerulonephritis (GN) World Health Organization (WHO) Classes III and IV. Less
      is known about MMF treatment of membranous SLE GN (WHO Class V, SLE MN). METHODS:
      We report our experience with MMF therapy in 13 consecutive SLE MN patients
      participating in a prospective study of risk factors for SLE flare. RESULTS:
      Baseline characteristics were: mean age 33 +/- 14 SD years, female/male ratio
      11/2, Caucasians 7, African Americans 5, Oriental 1, serum creatinine 1.02 +/-
      0.41, and mean 24-hour urine protein (P)/creatinine (C), ratio 5.1 +/- 4.1.
      Initial therapy was prednisone mean dose 31 +/- 17 mg/day, and MMF mean dose 1173
      +/- 746 mg/day. Therapy also featured interventions to achieve renoprotection and
      proteinuria reduction. At 6 months of therapy, complete or partial remission was
      achieved in 10 of 13 patients. At most recent follow-up visit (mean follow-up 16
      +/- 8 months), 9 of 13 patients were in complete remission, and in 11 of 13
      patients, urine P/C ratio was < 0.8. During follow-up, serum creatinine either
      stabilized or was improved. The only serious complication during 208 patient
      months of follow-up was histoplasma pneumonia in 1 patient. CONCLUSION: These
      promising results suggest that moderate dose MMF in combination with
      renoprotective/antiproteinuria therapy warrants further study in the management
      of SLE MN.

PMID- 15569334
TI  - Ethnicity and survival on dialysis in west London.
AB  - BACKGROUND: Indo-Asian and Afro-Caribbean patients have higher rates of renal
      failure and requirement for renal replacement therapy than the general population
      in the UK. Despite this, information regarding survival on dialysis is limited.
      METHODS: The incident hemodialysis population of a large west London renal
      service was reviewed from 1996 to 2001 (N = 465). RESULTS: The cohort's ethnic
      background was Indo-Asian (30.8%), Caucasian (49%), Afro-Caribbean (18.3%), and
      other (1.9%). Indo-Asians and Afro-Caribbeans were younger than Caucasian
      patients, with a higher rate of diabetes mellitus. Survival on hemodialysis for
      Indo-Asians was 97.5% and 81.6% at 1 and 3 years, respectively, compared with
      92.7% and 75.2% for Caucasians, and 97.5% and 85.3% for Afro-Caribbeans (P =
      nonsignificant). Dialysis adequacy was observed to be associated with survival.
      Patients with mean single pool Kt/V of over 1.4 had survival of 90.6% and 74.8%
      at 2 and 5 years, respectively, compared with 74.0% and 42.9% for those with Kt/V
      less than 1.4 (P < 0.001). There were significantly more patients in the Indo
      Asian cohort with a mean Kt/V of 1.4 or over (87.4%) compared with Caucasians
      (57.6%) and Afro-Caribbeans (52.4%), and the benefit of higher Kt/V was seen in
      all ethnic groups. In a multivariate analysis of factors including Kt/V over 1.4,
      age, diabetic status, gender, and ethnicity, Indo-Asian or Afro-Caribbean
      ethnicity did not confer a survival disadvantage. The strongest predictors of
      survival were age and dialysis adequacy. CONCLUSION: Indo-Asian and Afro
      Caribbean hemodialysis patients have survival comparable to Caucasians despite a
      higher burden of diabetes.

PMID- 15569335
TI  - Creatine supplementation does not decrease total plasma homocysteine in chronic
      hemodialysis patients.
AB  - BACKGROUND: Hyperhomocysteinemia is present in the majority of chronic
      hemodialysis patients. Treatment with folic acid, vitamin B12, and vitamin B6
      cannot fully normalize plasma homocysteine concentrations (tHcy). Previously we
      have demonstrated the tHcy-lowering effect of creatine supplementation in an
      animal model of uremia (Kidney Int 64:1331-1337, 2003). The present study
      investigates the effects of creatine supplementation on tHcy in a vitamin
      repleted chronic hemodialysis population. METHODS: Forty-five hemodialysis
      patients receiving folic acid and vitamin B6 and B12 were included. Patients were
      treated with creatine (2 g/day) or placebo during 2 treatment periods of 4 weeks,
      separated by a washout of 4 weeks. Plasma tHcy, creatine, Kt/V(urea), folic acid,
      vitamin B12, and routine biochemistry were determined, as well as the prognostic
      inflammatory and nutritional index. RESULTS: All patients had elevated tHcy
      concentrations (21.2 +/- 5.6 micromol/L). Creatine treatment resulted in
      increased plasma and red blood cell creatine levels, documenting uptake of
      creatine. Creatine did not affect tHcy concentrations. There was no relationship
      between plasma creatine concentrations and tHcy concentrations. No changes in
      body weight, routine biochemistry, nutritional status, folic acid, or vitamin B12
      were observed during the study. CONCLUSION: Creatine supplementation at a rate of
      2 g/day does not further decrease tHcy concentrations in chronic dialysis
      patients already treated with high dose folic acid, vitamin B6, and B12
      supplementation.

PMID- 15569336
TI  - Relationship among catheter insertions, vascular access infections, and anemia
      management in hemodialysis patients.
AB  - BACKGROUND: Arteriovenous fistulas are the recommended permanent vascular access
      (VA) for chronic hemodialysis. However, in the United States most patients begin
      chronic hemodialysis with a catheter. Recent data suggest that VA type
      contributes to recombinant human erythropoietin (rHuEPO) resistance. We examined
      catheter insertions, VA infections, and anemia management in Medicare, rHuEPO
      treated, chronic hemodialysis patients. METHODS: We compared hemoglobin values
      and rHuEPO and intravenous iron dosing with concurrent catheter insertions and VA
      infections in 186,348 period-prevalent patients in 2000. We studied anemia
      management after catheter insertions and VA infections in 67,410 incident
      patients from 1997 to 1999. Multiple linear regression models examined follow-up
      hemoglobin and rHuEPO dose per week (rHuEPO/wk) by numbers of catheter insertions
      and hospitalizations for VA infection. RESULTS: In the prevalent cohort,
      increasing temporary and permanent catheter insertions and VA infections were
      associated with slightly lower hemoglobin, higher rHuEPO doses, and higher
      intravenous iron doses. In the incident cohort, compared to patients with no VA
      infections or no catheter insertions (temporary or permanent), respectively,
      patients with 2+ VA infections or 2+ catheter insertions had 0.12 g/dL and 0.06
      g/dL lower mean hemoglobin (P = 0.0028 and P < 0.0001), and 25.7% and 12.2%
      higher mean rHuEPO/wk (P < 0.0001). CONCLUSION: Higher rHuEPO doses may be
      required to maintain similar or slightly lower mean hemoglobin values among
      chronic hemodialysis patients with higher numbers of catheter insertions and VA
      infections, compared to patients without any.

PMID- 15569337
TI  - Longitudinal relationship between solute transport and ultrafiltration capacity
      in peritoneal dialysis patients.
AB  - BACKGROUND: Time on treatment is associated with a greater risk of impaired
      ultrafiltration (UF) in peritoneal dialysis (PD) patients. In addition to
      increasing solute transport, a potentially treatable cause of impaired
      ultrafiltration, cross-sectional studies suggest that there is also reduced
      osmotic conductance of the membrane. If this were the case then it would be
      expected that the UF capacity for a given rate of solute transport would change
      with time. The purpose of this analysis was to establish how solute transport and
      UF capacity change relative to one another with time on therapy. METHODS:
      Membrane function, using a standard peritoneal equilibration test, was measured
      at least annually in a well-characterized, single-center observational cohort of
      PD patients between 1990 and 2003. Demography included age, gender, original
      cause of renal failure, body surface area (BSA), validated comorbidity score,
      residual urine volume and urea clearances, peritoneal urea clearances, and plasma
      albumin. RESULTS: Data from 574 new PD patients were available for analysis.
      Independent demographic factors associated with higher solute transport at
      baseline were male gender and higher residual urine volume. Throughout time on
      therapy there was a negative relationship between solute transport and UF
      capacity and a significant increase and decrease in these parameters,
      respectively. During the first 12 months of treatment, the increase in solute
      transport was not associated with the expected fall in UF capacity, a phenomenon
      that was not explained by informative censoring, but was associated with an
      increased, albeit weak, correlation with BSA. In contrast, later in treatment
      there was a disproportionate fall in UF capacity, more accelerated in patients
      developing UF failure. Early exposure to higher intraperitoneal glucose
      concentrations, in the context of more comorbidity and relative lack of residual
      renal function, was associated with more rapid deterioration in membrane
      function. CONCLUSION: Despite a causal link between solute transport and UF
      capacity of the membrane, due to the effect of the former on the osmotic
      gradient, there is evidence of their longitudinal dissociation. This implies a
      change in the structure-function relationship with time on treatment that can, to
      some extent, be predicted from clinical factors present within the first year of
      treatment. Dialysis-induced membrane injury must involve at least two processes,
      for example, increased vascular surface area contact with dialysate combined with
      changes in hydraulic conductance due to scarring of the vessels and interstitium.

PMID- 15569338
TI  - A prospective comparison of three argatroban treatment regimens during
      hemodialysis in end-stage renal disease.
AB  - BACKGROUND: We prospectively evaluated 3 treatment regimens of argatroban, a
      direct thrombin inhibitor, for providing adequate, safe anticoagulation in
      patients with end-stage renal disease (ESRD) during hemodialysis. METHODS: In
      this randomized, 3-way crossover study, ESRD patients underwent hemodialysis
      sessions of 3- or 4-hour duration using high-flux membranes and each of 3
      argatroban treatment regimens (A: 250-microg/kg bolus, with an additional 250
      microg/kg bolus allowed; B: 250-microg/kg bolus followed by 2-microg/kg/min
      infusion; C: steady-state, 2-microg/kg/min infusion initiated 4 hours before
      dialysis). Pharmacodynamic effects including activated clotting times (ACTs);
      hemodialysis efficacy including single-pool Kt/V, urea reduction ratio (URR), and
      circuit flow; and safety through a 3-day follow-up were monitored. Argatroban
      pharmacokinetic parameters including dialytic clearance were evaluated during
      regimen C. RESULTS: Thirteen patients completed 38 hemodialysis sessions (1
      patient withdrew consent after 2 sessions). Mean +/- SD ACTs increased from 131
      +/- 14 seconds at baseline to 153 +/- 24, 200 +/- 30, and 197 +/- 33 seconds,
      respectively, after 60 minutes of hemodialysis using regimens A, B, and C. Across
      regimens, mean Kt/Vs (1.5-1.6) and URRs (70%-73%) were comparable. No dialyzer
      was changed; 1 session was shortened 15 minutes because of circuit clot
      formation. Systemic argatroban clearance increased approximately 20% during
      hemodialysis, without clinically significantly affecting ACTs. Upon argatroban
      discontinuation, ACTs and plasma argatroban decreased concurrently (elimination
      half-life, 35 +/- 6 min). No thrombosis, bleeding, serious adverse events, or
      clinically significant changes in vital signs or routine laboratory measures
      occurred. CONCLUSION: Argatroban, administered by each treatment regimen,
      provides safe, adequate anticoagulation to enable successful hemodialysis in ESRD
      patients. Argatroban dialytic clearance by high-flux membranes is clinically
      insignificant.

PMID- 15569339
TI  - Plasma sodium and hypertension.
AB  - Dietary salt is the major cause of the rise in the blood pressure with age and
      the development of high blood pressure in populations. However, the mechanisms
      whereby salt intake raises the blood pressure are not clear. Existing concepts
      focus on the tendency for an increase in extracellular fluid volume (ECV), but an
      increased salt intake also induces a small rise in plasma sodium, which increases
      a transfer of fluid from the intracellular to the extracellular space, and
      stimulates the thirst center. Accordingly, the rise in plasma sodium is
      responsible for the tendency for an increase in ECV. Although the change in ECV
      may have a pressor effect, the associated rise in plasma sodium itself may also
      cause the blood pressure to rise. There is some evidence in patients with
      essential hypertension and the spontaneously hypertensive rat (SHR) that plasma
      sodium may be raised by 1 to 3 mmol/L. An experimental rise in sodium
      concentration greater than 5 mmol/L induces pressor effects on the brain and on
      the renin-angiotensin system. Such a rise can also induce changes in cultured
      vascular tissue similar to those that occur in the vessels of humans and animals
      on a high sodium diet, independent of the blood pressure. We suggest that a small
      increase in plasma sodium may be part of the mechanisms whereby dietary salt
      increases the blood pressure.

PMID- 15569340
TI  - Vascular calcification in ESRD: Another cloud appears in the perfect storm--but
      highlights a silver lining?

PMID- 15569342
TI  - Additional antiretroviral and immunosuppressive drug-drug interactions.

PMID- 15569344
TI  - The influence of plasma volume on blood pressure in regular hemodialysis
      patients.

PMID- 15569345
TI  - The changing face of schistosomal glomerulopathy.

PMID- 15569350
TI  - Cellular lifespan and senescence signaling in embryonic stem cells.
AB  - Most mammalian cells when placed in culture will undergo a limited number of cell
      divisions before entering an unresponsive non-proliferating state termed
      senescence. However, several pathways that are activated singly or in concert can
      allow cells to bypass senescence at least for limited periods. These include the
      telomerase pathway required to maintain telomere ends, the p53 and Rb pathways
      required to direct senescence in response to DNA damage, telomere shortening and
      mitogenic signals, and the insulin-like growth factor--Akt pathway that may
      regulate lifespan and cell proliferation. In this review, we summarize recent
      findings related to these pathways in embryonic stem (ES) cells and suggest that
      ES cells are immortal because these pathways are tightly regulated.

PMID- 15569351
TI  - Neural stem cells as therapeutic agents for age-related brain repair.
AB  - Neurogenesis occurs in two germinal centres of the adult brain and persists with
      increasing age, although at a reduced level. This observation, that the mature
      brain can support neurogenesis, has given rise to the hope that neural stem cells
      could be used to repair the brain by repopulating regions suffering from neuronal
      loss as a result of injury or disease. The aging brain is vulnerable to mild
      cognitive impairment, increasing incidence of stroke, and a variety of
      neurodegenerative diseases. However, most studies to date have focused on the
      young adult brain, and relatively little information is available about the
      regulation of neurogenesis in the aged brain or the potential of using neural
      stem cells to repair the aged brain. This review summarizes the current state of
      knowledge on neurogenesis in the young adult brain and discusses the information
      available on age-related changes in neurogenesis. Possible therapeutic strategies
      using neural stem cells for repair of the aging brain are considered.

PMID- 15569352
TI  - Alterations in the TGFbeta signaling pathway in myogenic progenitors with age.
AB  - Myogenic progenitors in adult muscle are necessary for the repair, maintenance
      and hypertrophy of post-mitotic muscle fibers. With age, fat deposition and
      fibrosis contribute to the decline in the integrity and functional capacity of
      muscles. In a previous study we reported increased accumulation of lipid in
      myogenic progenitors obtained from aged mice, accompanied by an up-regulation of
      genes involved in adipogenic differentiation. The present study was designed to
      extend our understanding of how aging affects the fate and gene expression
      profile of myogenic progenitors. Affymetrix murine U74 Genechip analysis was
      performed using RNA extracted from myogenic progenitors isolated from adult (8
      month-old) and aged (24-month-old) DBA/2JNIA mice. The cells from the aged
      animals exhibited major alterations in the expression level of many genes
      directly or indirectly involved with the TGFbeta signaling pathway. Our data
      indicate that with age, myogenic progenitors acquire the paradoxical phenotype of
      being both TGFbeta activated based on overexpression of TGFbeta-inducible genes,
      but resistant to the differentiation-inhibiting effects of exogenous TGFbeta. The
      overexpression of TGFbeta-regulated genes, such as connective tissue growth
      factor, may play a role in increasing fibrosis in aging muscle.

PMID- 15569353
TI  - Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on
      neural precursor cell populations in the adult murine hippocampus.
AB  - Steroid hormones are regulators of adult hippocampal neurogenesis and are central
      to hypotheses regarding adult neurogenesis in age-related and psychiatric
      disturbances associated with altered hippocampal plasticity--most notably
      dementias and major depression. Using immunohistochemistry, we examined the
      expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors during
      adult hippocampal neurogenesis. In young mice only 27% of dividing cells in the
      subgranular zone expressed GR, whereas 4 weeks after division 87% had become
      positive for GR and MR. GR was expressed by 50% of the radial glia-like type-1
      and type-2a progenitor cells, whereas MR was expressed only by mature calbindin
      positive granule cells. Doublecortin-positive neuronal progenitor cells (type-2b)
      and early postmitotic calretinin-positive neurons were devoid of GR and MR
      expression. Fifty per cent of the intermediate type-3 cells showed GR expression,
      possibly reflecting cells terminating maturation. Thus, all subpopulations of
      dividing precursor cells showed an identical receptor profile (50% GR, no MR),
      except for type-2b cells, which expressed neither receptor. There was also no
      overlap between calretinin and GR early postnatally (P8) or after physical
      activity or exposure to an enriched environment, both of which are potent
      neurogenic stimuli. In contrast, in old age calretinin-positive young neurons
      became GR and MR positive, suggesting increased steroid sensitivity. Age also
      increased the expression of GR in type-1 and type-2a precursor cells. Other
      intermediates were so rare in old age that they could not be studied. This course
      and variability of receptor expression in aging might help to explain
      differential vulnerability of adult neural precursor cells to corticoid-mediated
      influences.

PMID- 15569354
TI  - Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain.
AB  - The adult mammalian brain retains the capacity for neurogenesis, by which new
      neurons may be generated to replace those lost through physiological or
      pathological processes. However, neurogenesis diminishes with aging, and this
      casts doubt on its feasibility as a therapeutic target for cell replacement
      therapy in stroke and neurodegenerative disorders, which disproportionately
      affect the aged brain. In previous studies, neurogenesis was stimulated by
      cerebral ischemia in young rodents, and the neurogenesis response of the aged
      rodent brain to physiological stimuli, such as hormonal manipulation and growth
      factors, was preserved. To investigate the effect of aging on ischemia-induced
      neurogenesis, transient (60 min) middle cerebral artery occlusion was induced in
      young adult (3-month) and aged (24-month) rats, who were also given
      bromodeoxyuridine to label newborn cells. As found in prior studies, basal
      neurogenesis in control, nonischemic rats was reduced with aging. Ischemia failed
      to stimulate neurogenesis in the dentate gyrus (DG) subgranular zone (SGZ), in
      contrast to results obtained previously after more prolonged (90-120 min) middle
      cerebral artery occlusion, but increased the number of BrdU-labeled cells in the
      forebrain subventricular zone (SVZ). This effect was less prominent in aged than
      in young adult rats, with fold-stimulation of BrdU incorporation reduced by
      approximately 20% and the total number of cells generated diminished by
      approximately 50%. BrdU-labeled cells in SVZ coexpressed neuronal lineage
      markers, consistent with newborn neurons. We conclude that ischemia-induced
      neurogenesis occurs in the aged brain, and that measures designed to augment this
      phenomenon might have therapeutic applications.

PMID- 15569356
TI  - Accumulation of mutations and somatic selection in aging neural stem/progenitor
      cells.
AB  - Genomic instability within somatic stem cells may lead to the accumulation of
      mutations and contribute to cancer or other age-related phenotypes. However,
      determining the frequency of mutations that differ among individual stem cells is
      difficult from whole tissue samples because each event is diluted in the total
      population of both stem cells and differentiated tissue. Here the ability to
      expand neural stem/progenitor cells clonally permitted measurement of genomic
      alterations derived from a single initial cell. C57Bl/6 x DBA/2 hybrid mice were
      used and PCR analysis with strain-specific primers was performed to detect loss
      of heterozygosity on nine different chromosomes for each neurosphere. The
      frequency with which changes occurred in neurospheres derived from 2-month- and 2
      year-old mice was compared. In 15 neurospheres derived from young animals both
      parental chromosomes were present for all nine chromosome pairs. In contrast,
      16/17 neurospheres from old animals demonstrated loss of heterozygosity (LOH) on
      one or more chromosomes and seven exhibited a complete deletion of at least one
      chromosomal region. For chromosomes 9 and 19 there is a significant bias in the
      allele that is lost where in each case the C57Bl/6 allele is retained in 6/6
      neurospheres exhibiting LOH. These data suggest that aging leads to a substantial
      mutational load within the neural stem cell compartment which can be expected to
      affect the normal function of these cells. Furthermore, the retention of specific
      alleles for chromosomes 9 and 19 suggests that a subset of mutational events lead
      to an allele-specific survival advantage within the neural stem cell compartment.

PMID- 15569355
TI  - Aging activates adipogenic and suppresses osteogenic programs in mesenchymal
      marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF
      beta/BMP signaling pathways.
AB  - Osteoblasts and adipocytes originate from a common progenitor, which arises from
      bone marrow mesenchymal stroma/stem cells (mMSC). Aging causes a decrease in the
      number of bone-forming osteoblasts and an increase in the number of marrow
      adipocytes. Here, we demonstrate that, during aging, the status of mMSC changes
      with respect to both their intrinsic differentiation potential and production of
      signaling molecules, which contributes to the formation of a specific marrow
      microenvironment necessary for maintenance of bone homeostasis. Aging causes a
      decrease in the commitment of mMSC to the osteoblast lineage and an increase in
      the commitment to the adipocyte lineage. This is reflected by changes in the
      expression of phenotype-specific gene markers. The expression of osteoblast
      specific transcription factors, Runx2 and Dlx5, and osteoblast markers, collagen
      and osteocalcin, is decreased in aged mMSC. Conversely, the expression of
      adipocyte-specific transcription factor PPAR-gamma2, shown previously to regulate
      osteoblast development and bone formation negatively and to regulate marrow
      adipocyte differentiation positively, is increased, as is a gene marker of
      adipocyte phenotype, fatty acid binding protein aP2. Furthermore, production of
      an endogenous PPAR-gamma activator(s) that stimulates adipocyte differentiation
      and production of autocrine/paracrine factor(s) that suppresses the osteoblastic
      phenotype are also increased. In addition, expression of different components of
      TGF-beta and BMP2/4 signaling pathways is altered, suggesting that activities of
      these two cytokines essential for bone homeostasis change with aging.

PMID- 15569357
TI  - Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage.
AB  - Telomerase is often re-activated in human cancers and is widely used to
      immortalize cells in culture. In addition to the maintenance of telomeres,
      telomerase has been implicated in cell proliferation, genomic instability and
      apoptosis. Here we show that human telomerase reverse transcriptase (hTERT) is
      targeted to the mitochondria by an N-terminal leader sequence, and that
      mitochondrial extracts contain telomerase activity. In seven different human cell
      lines, mitochondrial telomerase increases hydrogen-peroxide-mediated
      mitochondrial DNA damage. hTERT expression did not alter the rate of hydrogen
      peroxide breakdown or endogenous cellular levels. Because the damaging effects of
      hydrogen peroxide are mediated by divalent metal ions (Fenton chemistry), we
      examined the levels of bioavailable metals. In all cases, higher levels of
      chelatable metals were found in hTERT-expressing cells. These results suggest
      that mitochondrial telomerase sensitizes cells to oxidative stress, which can
      lead to apoptotic cell death, and imply a novel function of telomerase in
      mitochondrial DNA transactions.

PMID- 15569358
TI  - Lipophilic regulator of a developmental switch in Caenorhabditis elegans.
AB  - Abstract In Caenorhabditis elegans, the decision to develop into a reproductive
      adult or arrest as a dauer larva is influenced by multiple pathways including
      insulin-like and transforming growth factor beta (TGFbeta)-like signalling
      pathways. It has been proposed that lipophilic hormones act downstream of these
      pathways to regulate dauer formation. One likely target for such a hormone is DAF
      12, an orphan nuclear hormone receptor that mediates these developmental
      decisions and also influences adult lifespan. In order to find lipophilic
      hormones we have generated lipophilic extracts from mass cultures of C. elegans
      and shown that they rescue the dauer constitutive phenotype of class 1 daf-2
      insulin signalling mutants and the TGFbeta signalling mutant daf-7. These
      extracts are also able to rescue the lethal dauer phenotype of daf-9 mutants,
      which lack a P450 steroid hydroxylase thought to be involved in the synthesis of
      the DAF-12 ligand; extracts, however, have no effect on a DAF-12 ligand binding
      domain mutant that is predicted to be ligand insensitive. The production of this
      hormone appears to be DAF-9 dependent as extracts from a daf-9;daf-12 double
      mutant do not exhibit this activity. Preliminary fractionation of the lipophilic
      extracts shows that the activity is hydrophobic with some polar properties,
      consistent with a small lipophilic hormone. We propose that the dauer rescuing
      activity is a hormone synthesized by DAF-9 that acts through DAF-12.

PMID- 15569359
TI  - Gene expression profile of long-lived Ames dwarf mice and Little mice.
AB  - Ames dwarf mice (Prop1df/df) and Little mice (Ghrhrlit/lit) are used as models of
      delayed aging and show significant increases in lifespan (50% and 25%,
      respectively) when compared with their wild-type siblings. To gain further
      insight into the molecular basis for the extended longevity of these mice, we
      used oligonucleotide microarrays to measure levels of expression of over 14 000
      RNA transcripts in liver during normal aging at 3, 6, 12 and 24 months. We found
      that the Prop1df/df and Ghrhrlit/lit genotypes produce dramatic alterations in
      gene expression, which are predominantly maintained at all ages. We found 1125
      genes to be significantly affected by the Prop1df/df genotype and 1152 genes were
      significantly affected by the Ghrhrlit/lit genotype; 547 genes were present in
      both gene lists and showed parallel changes in gene expression, suggesting common
      mechanisms for the extended longevity in these mutants. Some of the functional
      gene classes most affected in these mutants included: amino acid metabolism, TCA
      cycle, mitochondrial electron transport, fatty acid, cholesterol and steroid
      metabolism, xenobiotic metabolism and oxidant metabolism. We found that the
      Prop1df/df genotype, and to a minor extent the Ghrhrlit/lit genotype, also
      produced complex alterations in age-dependent changes in gene expression as
      compared with wild-type mice. In some cases these alterations reflected a partial
      delay or deceleration of age-related changes in gene expression as seen in wild
      type mice but they also introduced age-related changes that are unique for each
      of these mutants and not present in wild-type mice.

PMID- 15569360
TI  - The G/C915 polymorphism of transforming growth factor beta1 is associated with
      human longevity: a study in Italian centenarians.
AB  - Sequence variations in a variety of pro- or anti-inflammatory cytokine genes have
      been found to influence successful aging and longevity. Because of the role
      played by the transforming growth factor beta1 (TGF-beta1) cytokine in
      inflammation and regulation of immune responses, the variability of the TGF-beta1
      gene may affect longevity by playing a role in inflamm-aging. Two polymorphisms,
      G/A -800 and C/T -509, located in the 5' region, and two missense polymorphisms,
      T/C 869 and G/C 915 which change (Leu > Pro)10 and (Arg > Pro)25, respectively,
      located in the signal peptide, were analysed in 419 subjects from Northern and
      Central Italy, including 172 centenarians and 247 younger controls. In addition,
      the effects of the TGF-beta1 genetic variability on plasma levels of the
      biologically active form (naturally processed) of this cytokine were studied in
      143 randomly selected subjects, including 73 centenarians. Significant
      differences were found at the +915 site as far as the C allele and GC genotype
      were concerned, both of them being lower in centenarians than in young controls
      (P=0.034 and 0.028, respectively), but none of the other tested genetic variants
      was significantly different between centenarians and controls. Moreover, a
      particular haplotype combination (G -800/C -509/C 869/C 915) was notably lower in
      centenarians than in younger individuals (P=0.007). Finally, active TGF-beta1
      plasma levels were significantly increased in the elderly group, but no
      relationship with TGF-beta1 genotypes was observed. These results suggest that,
      at least in this population, the variability of the TGF-beta1 gene influences
      longevity and that the age-related increase in plasma levels of active TGF-beta1
      seems not to be genetically regulated.

PMID- 15569362
TI  - Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride
      in therapy of gastroesophageal reflux disease: a randomized trial.
AB  - The present study aimed to compare the efficacy for the therapy of GERD of
      pantoprazole alone with a combination of pantoprazole and mosapride. The study
      was a prospective, randomized trial involving 68 patients suffering heartburn
      and/or regurgitation at least twice a week for 6 weeks. Sixty-one patients
      consented to be randomized to receive either pantoprazole 40 mg b.i.d. (n = 33,
      group A) or pantoprazole 40 mg b.i.d. plus mosapride 5 mg t.d.s. (n = 28, group
      B) for 8 weeks. Twenty-four-hour esophageal pH-metry and endoscopy were conducted
      at recruitment and endoscopy was repeated at 8 weeks in all the patients studied.
      There were no differences in symptomatic responses to therapy between the groups
      (69.7% vs 89.2%; P = 0.11). The mean symptom score after 8 weeks was
      significantly lower in group B (3.78 +/- 3.62 vs 1.67 +/- 2.09; P = 0.009).
      Nonerosive esophagitis was present in 29 patients. In patients with nonerosive
      GERD there was no significant difference in symptomatic response to either
      regimen (17/20 in group A and 7/9 in group B responded; P = 0.63). In erosive
      esophagitis, symptomatic responses occurred more frequently in group B, 18/19
      (94.7%), than in group A, 6/13 (46.2%; P = 0.003). However endoscopic healing of
      esophagitis occurred equally with either regimen (6/11, 54.5% in group A; 12/17,
      70.5% in group B; P = 0.44). In nonerosive GERD, the addition of mosapride offers
      no benefit over pantoprazole alone. A combination of pantoprazole and mosapride
      is more effective than pantoprazole alone in providing symptomatic relief to
      patients with erosive GERD.

PMID- 15569363
TI  - Symptomatic and radiological follow-up after para-esophageal hernia repair.
AB  - The treatment of para-esophageal hernia by the laparoscopic approach has been
      described by a number of authors. The lower morbidity of the laparoscopic
      approach compared with the open approach holds some attraction, however,
      reservations regarding the durability of laparoscopic repair exist. There is a
      paucity of objective follow-up data in the literature with regard to repair
      durability and symptomatic outcome. A review was undertaken of 94 patients over a
      7 year period undergoing attempted laparoscopic repairs of para-esophageal
      hernia. Preoperative and operative data was collected and patients underwent
      postoperative interview and barium meal. Laparoscopic repair was successfully
      completed in 86 patients. Symptomatic reherniation occurred in 12% (10/86) of
      patients undergoing laparoscopic repair. These patients underwent open
      reoperative surgery. There were no symptomatic recurrences in patients undergoing
      initial open repair. Symptomatic outcome was assessed by interview in 78% (73/94)
      of patients at a median of 27 months (3-93 months) postoperatively. Ninety-seven
      percent (71/73) of patients were satisfied with their ultimate symptomatic
      outcome however, this group included seven patients who had required reoperative
      surgery for symptomatic recurrence and were therefore laparoscopic failures. In
      order to determine the asymptomatic recurrence rate patients were requested to
      undergo a barium meal. A further nine small asymptomatic recurrences were
      diagnosed in 42 patients having had laparoscopic repair. This represents an
      asymptomatic radiographic recurrence rate of 21%. Laparoscopic repair in this
      series was associated with a 12% symptomatic recurrence rate. The majority of
      patients with symptomatic recurrence underwent open reoperation with good
      results. Strategies for reducing recurrences should be examined in prospective
      series.

PMID- 15569364
TI  - Prevalence of esophageal disorders in patients with recurrent chest pain.
AB  - The objective of this study is to determine the prevalence of esophageal
      disorders (ED) associated with recurrent chest pain (RCP) and the utility of
      esophageal functional tests (EFT) in the study of these patients. The cross
      sectional study was conducted at Hospital Clinico de La Frontera, Chile. One
      hundred and twenty-three patients with RCP were studied using esophageal
      manometry, edrophonium stimulation and 24-h pH monitoring. The performance of EFT
      was considered acceptable when they were capable of finding ED. To state the
      probability that RCP had an esophageal origin, patients were classified according
      to whether their pain had a probable, possible or unlikely esophageal origin. The
      prevalence of ED was determined according to diagnoses obtained after applying
      EFT and a multivariate analysis was performed to examine the association between
      the esophageal origin of RCP and ED. Rates of correct diagnosis of 65.9%, 56.9%
      and 31.7% was verified for 24-h pH monitoring, esophageal manometry and
      edrophonium stimulation, respectively. In 38.2% of patients with RCP, the pain
      was probably of esophageal origin, in 42.3% there was a possible esophageal
      origin and in 19.5% an unlikely esophageal origin. A 44.7% prevalence of GERD,
      26.8% of GERD with secondary esophageal motor dysfunction and 8.9% of pure
      esophageal motor dysfunction were verified. The multivariate analysis allowed us
      to verify the association between the probability of esophageal origin of RCP,
      the variables RCP duration, esophagitis and dysphagia coexistence (P= 0.037, P=
      0.030 and P= 0.024, respectively), and a statistically significant association
      between ED and dysphagia coexistence (P= 0.028). A high prevalence of ED was
      identified in patients with RCP.

PMID- 15569365
TI  - Investigating four 'myths' surrounding dysphagia in patients with metastatic
      esophageal cancer. A multi-institutional study from the North Central Cancer
      Treatment Group.
AB  - Eighty-five to 95% of esophageal cancer patients suffer dysphagia. Yet, few
      studies have focused on this symptom, and four 'myths' persist: (i) dysphagia
      cannot be measured; (ii) chemotherapy cannot palliate it; (iii) dysphagia
      predicts a poor prognosis; (iv) dysphagia is associated with a frustratingly
      insatiable appetite. Forty-four patients with metastatic esophageal cancer
      participated in this quality of life/translational component of a previously
      reported clinical trial. All were monitored for chemotherapy efficacy and
      toxicity and completed questionnaires on dysphagia and appetite at baseline and
      every 6 weeks. The appetite hormones, leptin and neuropeptide y, were also
      assessed. Forty-five per cent of patients could easily swallow solid foods; all
      others had varying dysphagia, thus enabling exploration of these four 'myths.'
      First, a single-item visual analog scale (Swallowing Scale), demonstrated
      excellent agreement with a previously validated questionnaire (81% at baseline),
      thus reminding us that dysphagia is measurable. Second, chemotherapy was
      associated with a trend towards improved dysphagia (P = 0.059). Third, dysphagia
      did not predict tumor response or survival. Fourth, dysphagia was not associated
      with appetite, leptin or neuropeptide y. This study helps to dispel these four
      'myths' and underscores the need for further quality of life research on
      dysphagia.

PMID- 15569366
TI  - 'Efficacy' of esophageal peristalsis: a manometric parameter to quantify
      esophageal body dysfunction.
AB  - Esophageal motor abnormalities are currently categorized into separate entities
      based on standard manometry. The clinical significance of these categories is
      controversial. We evaluated whether ambulatory 24-h esophageal motility
      monitoring improves the assessment of patients thought to have a primary
      esophageal motor disorder. Standard and ambulatory 24-h esophageal motility
      records of 30 healthy volunteers and 136 symptomatic patients were compared.
      Regression analysis was used to identify parameters that relate to the presence
      of nonobstructive dysphagia. Prolonged ambulatory esophageal monitoring showed a
      marked circadian variation in the esophageal motor pattern and significant
      discrepancies to the findings on standard manometry in 47% of the 136 patients.
      Discrepancies were particularly frequent in patients categorized on standard
      manometry as having a 'nutcracker esophagus' or a nonspecific motor disorder. Of
      all data obtained, the prevalence of 'effective contractions', i.e. peristaltic
      contractions with an amplitude > 30 mmHg, during meal periods provided the best
      correlation with the presence of nonobstructive dysphagia. Of the 78 patients
      with nonobstructive dysphagia 71 (92%) had less than 50% of 'effective
      contractions' during meals. In five patients who had frequent simultaneous wave
      forms and less than 70%'effective contractions' during meals a long myotomy
      markedly reduced the severity of dysphagia. The 'efficacy' of esophageal
      contractions during meals best relates to patients' symptoms and allows
      expression of esophageal body dysfunction on a linear scale. This obviates the
      need for the current categories of esophageal motor disorders, permits an
      objective assessment of medical therapy and may improve the identification of
      patients that benefit from a surgical myotomy of the esophageal body.

PMID- 15569367
TI  - Pathological validity of esophageal endoscopy. How real is what we see? Myth or
      reality?
AB  - The purpose of this study was to characterize the spectrum of esophageal
      pathology at a provincial tertiary care hospital and to evaluate these findings
      with their respective endoscopic diagnoses. The pathology slides of 183
      esophageal biopsies for the year 2000 were reviewed and classified as
      esophagitis, intestinal metaplasia, low or high grade dysplasia, adenocarcinoma,
      squamous cell carcinoma or normal. One hundred and fifteen cases (63%) had
      complete concordant results with respective endoscopic reports. Sixty-eight cases
      (37%) had discordant results with inaccurate recognition of Barrett's esophagus
      in 9% and of esophagitis with a false positive in 16% and false negative in 7%.
      Although esophagoscopy remains a primary investigative tool in gastroesophageal
      diseases, evaluation of erythema, inflammation and esophagitis can be misleading.
      Pathologically confirmed esophagitis can occur in a 'normal' esophagus. Accurate
      endoscopic recognition of short-segment Barrett's remains a diagnostic challenge.

PMID- 15569368
TI  - Influence of transposed stomach on cardiac function in patients with resected
      esophageal cancer.
AB  - Although the use of the posterior mediastinum and the stomach as a reconstruction
      option after esophagectomy has wide acceptance, there are concerns about the
      potential cardiac impairment it could cause. We prospectively studied 27 patients
      regarding the function and the systolic diameter, diastolic diameter, shortening
      fraction, ejection fraction and the presence of extrinsic compression. The
      patients were studied preoperatively and between the 45th and 60th postoperative
      days. The parameters were still within normal clinical ranges. We concluded that
      this type of reconstruction does not harm the patients in terms of their cardiac
      function.

PMID- 15569369
TI  - High volume centers for esophagectomy: what is the number needed to achieve low
      postoperative mortality?
AB  - Aimed at reducing surgical deaths, several initiatives have attempted to
      establish volume-based referral strategies in high risk surgery. The detailed
      analysis of the literature of the last 10 years, comprising 13 papers on
      esophageal cancer, shows a clear reduction in postoperative mortality with
      increasing case volumes per year. Single papers have analyzed the main reasons
      for this phenomenon and showed that postoperative complication rates are lower in
      high-volume hospitals and management of complications is more successful.
      Further, long-term prognosis is also correlated to case-volume. In conclusion,
      the analysis shows that only with the experience of more than 20 esophagectomies
      per year can a significant reduction of the mortality, down to 4.9%, be achieved.
      Based on this survey, surgery of esophageal cancer is a task for high-volume
      hospitals because of decreased postoperative mortality and improved long-term
      prognosis compared with low volume hospitals.

PMID- 15569370
TI  - Expression of p21(Waf1/Cip1) predicts response and survival of esophageal cancer
      patients treated by chemoradiotherapy.
AB  - Chemoradiotherapy is a multimodal therapy routinely used as a primary treatment
      for advanced esophageal cancer. However, it is beneficial only to patients who
      respond. To identify pretreatment markers predicting response and survival, we
      examined the expression of cell cycle regulatory molecules, p53, p21(Waf1/Cip1)
      cyclin D1, and CDC25B, in biopsy specimens from 76 patients with stage III and
      stage IV squamous cell carcinoma. Overexpression of p53, p21, cyclin D1 and
      CDC25B was observed in 58%, 30%, 28%, and 32% of patients, respectively. The
      expression of p21 correlated significantly with response to chemoradiotherapy (P
      = 0.0001). Survival of patients with p21-expressing tumors was better than that
      of patients with p21-negative tumors (P = 0.013). Expression of other genes was
      not significantly correlated with treatment response and survival. In patients
      with p53-negative tumors, survival of those patients with p21-positive tumors was
      significantly higher than that of those with p21-negative tumors (P = 0.0452),
      but no significant difference was found in patients with p53-positive tumors.
      Multivariate analysis revealed that p21 expression was an independent variable
      among pretreatment parameters in predicting survival. These results suggest that
      p21 expression is potentially useful for predicting the response to
      chemoradiotherapy and survival of patients with advanced esophageal squamous cell
      cancer.

PMID- 15569371
TI  - Malignant degeneration of Barrett's esophagus: the role of the Ki-67
      proliferation fraction, expression of E-cadherin and p53.
AB  - Barrett's columnar epithelium with dysplasia is the most important risk factor
      for adenocarcinoma of the distal esophagus. The molecular mechanisms responsible
      for progression of columnar metaplasia to dysplasia and invasive carcinoma are
      mostly unknown. We investigated expression of the tumor suppressor gene p53, E
      cadherin expression and cell proliferation in the metaplasia-dysplasia-carcinoma
      sequence of esophageal adenocarcinoma. In 24 patients with R0-resected
      adenocarcinomas of the distal esophagus we evaluated the expression of E-cadherin
      (antibody HECD-1), mutated p53 (antibody DO1) and cell proliferation (antibody
      MiB1) by immunohistochemistry in sections of adenocarcinoma, columnar metaplasia,
      with and without dysplasia, and in squamous epithelium of the esophagus. No p53
      immunoreactivity was seen in sections of normal squamous epithelium or columnar
      metaplasia. Fifty per cent of invasive adenocarcinomas stained positive for
      mutated p53. The p53 expression correlated with the T-category (P = 0.048) and
      the N-category (P = 0.024). There was a significant decrease in the expression of
      E-cadherin from columnar metaplasia to dysplasia and to esophageal adenocarcinoma
      (P < 0.0001). Expression of E-cadherin in columnar metaplasia without dysplasia
      was similar to that seen in normal squamous epithelium of the esophagus. The Ki
      67 proliferation fraction increased significantly from normal squamous epithelium
      to columnar metaplasia to dysplasia and to invasive carcinoma (P < 0.001), with a
      marked expansion of the proliferative component. There was no correlation between
      cell proliferation, E-cadherin expression and the tumor stage. In contrast to the
      alterations in the p53 expression, a decreased E-cadherin expression and the
      expansion of the proliferative component represent an early phenomenon in the
      malignant degeneration of Barrett's esophagus. This might aid in the early
      detection of esophageal adenocarcinoma.

PMID- 15569372
TI  - Clinical significance of bone marrow micrometastases in esophageal cancer.
AB  - Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we
      investigated the clinical significance of bone marrow micrometastases in patients
      with esophageal cancer. Bone marrow samples from 57 patients with esophageal
      cancer, who underwent esophagotomy, were investigated by specific RT-PCR for
      carcinoembryonic antigens (CEA). A total of 40 out of 57 patients (70.1%) were
      positive for CEA mRNA in the bone marrow. Among curatively resected cases, 34 of
      50 patients (68.0%) were positive for CEA. Ten of 13 T1 patients (76.9%) were
      positive for CEA. Although the CEA-positive rate was high, there was no
      significant correlation between CEA positivity and any clinical characteristics.
      Among the 40 CEA-positive patients, 50% have shown recurrence so far. Detection
      of cancer cells in the bone marrow by RT-PCR may not always correspond to the
      malignant potential or other characteristics of the tumor. CEA-positive
      'micrometastases' might actually represent isolated circulating tumor cells
      without much biological significance.

PMID- 15569373
TI  - Tumor budding as a useful prognostic marker in esophageal squamous cell
      carcinoma.
AB  - We examined the prognostic significance of tumor budding in patients with
      esophageal squamous cell carcinoma, particularly in comparison to other routine
      pathological findings. Fifty-six cases who underwent an esophagectomy were
      reviewed. We defined tumor budding as an isolated single cancer cell or a cluster
      composed of fewer than five cancer cells and divided these into two grades; low
      grade (< 5 budding foci) and high-grade (> or = 5 budding foci) within a
      microscopic field of x 200. There were 22 (39.3%) and 34 (60.7%) cases with low-
      and high-grade budding, respectively. There were significant differences in the
      patients with low- and high-grade budding in relation to tumor size, pT stage,
      lymphovascular invasion, perineural invasion, circumferential resection margin
      involvement, and AJCC stage (P < 0.05). The 3-year survival rates of the patients
      with low- and high-grade budding were 72.3% and 30.7%, respectively (P = 0.04).
      We propose that tumor budding may be a pathological marker suggesting high
      malignancy potential and decreased postoperative survival in patients with
      esophageal squamous cell carcinoma.

PMID- 15569374
TI  - Flavopiridol as a radio-sensitizer for esophageal cancer cell lines.
AB  - Flavopiridol is a synthetic flavone that has shown an antitumor effect against
      several cancers. Here, we investigated the in vitro effect of flavopiridol alone
      and the combined effect of low-dose flavopiridol plus radiation on esophageal
      squamous cell carcinoma cell lines. Esophageal squamous cell carcinoma cell lines
      (TE8, TE9 and KE4) were exposed to flavopiridol (0.05-400 nmol/L) for 48 h.
      Growth inhibition was evaluated by MTT assay, cell cycle distribution was
      determined by flow cytometry, and cyclin D1, Bcl-2 and Rb protein expression was
      detected by Western blotting. The effect of 0.05 nmol/L flavopiridol as a radio
      sensitizer was determined by clonogenic assay. The IC50 was approximately 110-250
      nmol/L. Exposure to 0.05 nmol/L flavopiridol for 48 h increased the G2/M
      population, while 300 nmol/L increased the G1 population. At a concentration of
      300 nmol/L, nuclear fragmentation and chromatin condensation were observed in all
      three cell lines. Exposure to 300 nmol/L flavopiridol decreased the levels of
      cyclin D1 and Rb protein in all three cell lines and Bcl-2 protein was also
      decreased in TE8 and KE4 cells. Moreover, exposure to 0.05 nmol/L flavopiridol
      slightly decreased the levels of cyclin D1, Rb and Bcl-2 protein in KE4 cells.
      Flavopiridol treatment (0.05 nmol/L) enhanced the radio-sensitivity in all three
      cell lines. Low-dose flavopiridol augmented the response of esophageal squamous
      cell carcinoma cell lines to radiation. Administration of a low dose of
      flavopiridol could be a potent new therapeutic approach for improving the
      efficacy of radiotherapy against esophageal cancer.

PMID- 15569375
TI  - Esophageal papillomatosis complicated by squamous cell carcinoma in situ.
AB  - We present a case of esophageal papillomatosis with underlying squamous cell
      carcinoma in situ. An esophageal lesion resected from a 74-year-old woman
      demonstrated histological findings characteristic of squamous cell papilloma
      (fibrovascular core and numerous finger-like projections covered with
      hyperplastic squamous epithelium) and severe dysplasia characteristic of squamous
      cell carcinoma. The relation of squamous papilloma and squamous cell carcinoma is
      discussed. It is suggested that esophageal squamous cell papilloma is a
      premalignant lesion.

PMID- 15569376
TI  - Endoscopic placement of fibrin sealant as a treatment for a long-standing
      Boerhaave's fistula.
AB  - A 64-year-old man suffered a spontaneous rupture of the esophagus (Boerhaave's
      syndrome) after an episode of severe retching. He underwent attempted primary
      repair of the esophageal defect, but unfortunately the repair failed with the
      development of a persistent esophago-bronchial fistula resistant to extended
      conservative management. Three hundred and nineteen days after the initial
      rupture, the fistula was successfully treated with endoscopic placement of fibrin
      glue. We believe this to be the first reported case of fibrin sealant being used
      in the treatment of a long-standing fistula resulting from Boerhaave's syndrome.

PMID- 15569378
TI  - Famine intensity and magnitude scales: a proposal for an instrumental definition
      of famine.
AB  - Ambiguities in current usage of the term "famine" have had tragic implications
      for response and accountability in a number of recent food crises. This paper
      proposes a new approach to defining famine based on the use of intensity and
      magnitude scales, where "intensity" refers to the severity of the crisis at a
      given location and point in time, while "magnitude" describes the aggregate
      impact of a crisis. The scales perform three operations on "famine": first,
      moving from a binary conception of "famine/no famine" to a graduated, multi-level
      definition; second, disaggregating the dimensions of intensity and magnitude; and
      third, assigning harmonised "objective" criteria in place of subjective, case-by
      case judgements. If adopted, the famine scales should contribute to more
      effective and proportionate responses, as well as greater accountability in
      future food crises.

PMID- 15569379
TI  - "We all knew that a cyclone was coming": disaster preparedness and the cyclone of
      1999 in Orissa, India.
AB  - Imagine that a cyclone is coming, but that those living in the affected areas do
      nothing or too little to protect themselves. This is precisely what happened in
      the coastal state of Orissa, India. Individuals and communities living in regions
      where natural hazards are a part of daily life develop strategies to cope with
      and adapt to the impacts of extreme events. In October 1999, a cyclone killed
      10,000 people according to government statistics, however, the unofficial death
      toll is much higher. This article examines why such a large loss of life occurred
      and looks at measures taken since then to initiate comprehensive disaster
      preparedness programmes and to construct more cyclone shelters. The role of both
      governmental organisations and NGOs in this is critically analysed. The good news
      is that, based on an assessment of disaster preparedness during a small cyclone
      in November 2002, it can be seen that at community-level awareness was high and
      that many of the lessons learnt in 1999 were put into practice. Less positive,
      however, is the finding that at the state level collaboration continues to be
      problematic.

PMID- 15569380
TI  - The health sector gap in the southern Africa crisis in 2002/2003.
AB  - The southern Africa crisis represents the first widespread emergency in a region
      with a mature HIV/AIDS epidemic. It provides a steep learning curve for the
      international humanitarian system in understanding and responding to the complex
      interactions between the epidemic and the causes and the effects of this crisis.
      It also provoked much debate about the severity and causes of this emergency, and
      the appropriateness of the response by the humanitarian community. The authors
      argue that the over-emphasis on food aid delivery occurred at the expense of
      other public health interventions, particularly preventative and curative health
      services. Health service needs were not sufficiently addressed despite the early
      recognition that ill-health related to HIV/AIDS was a major vulnerability factor.
      This neglect occurred because analytical frameworks were too narrowly focused on
      food security, and large-scale support to health service delivery was seen as a
      long-term developmental issue that could not easily be dealt with by short-term
      humanitarian action. Furthermore, there were insufficient countrywide data on
      acute malnutrition, mortality rates and performance of the public health system
      to make better-balanced evidence-based decisions. In this crisis, humanitarian
      organisations providing health services could not assume their traditional roles
      of short-term assistance in a limited geographical area until the governing
      authorities resume their responsibilities. However, relegating health service
      delivery as a long-term developmental issue is not acceptable. Improved
      multisectoral analytical frameworks that include a multidisciplinary team are
      needed to ensure all aspects of public health are dealt with in similar future
      emergencies. Humanitarian organisations must advocate for improved delivery and
      access to health services in this region. They can target limited geographical
      areas with high mortality and acute malnutrition rates to deliver their services.
      Finally, to address the underlying problem of the health sector gap, a long-term
      strategy to ensure improved and sustainable health sector performance can only be
      accomplished with truly adequate resources. This will require renewed efforts on
      part of governments, donors and the international community. Public health
      interventions, complementing those addressing food insecurity, were and are still
      needed to reduce the impact of the crisis, and to allow people to re-establish
      their livelihoods. These will increase the population's resilience to prevent or
      mitigate future disasters.

PMID- 15569381
TI  - Effects of a tropical cyclone on the drinking-water quality of a remote Pacific
      island.
AB  - The effect of a cyclone (Ami, January 2003) on drinking-water quality on the
      island of Vanua Levu, Fiji was investigated. Following the cyclone nearly three
      quarters of the samples analysed did not conform to World Health Organisation
      (WHO) guideline values for safe drinking-water in terms of chlorine residual,
      total and faecal coliforms, and turbidity. Turbidity and total coliform levels
      significantly increased (up 56 and 62 per cent, respectively) from pre-cyclone
      levels, which was likely due to the large amounts of silt and debris entering
      water-supply sources during the cyclone. The utility found it difficult to
      maintain a reliable supply of treated water in the aftermath of the disaster.
      Communities were unaware they were drinking water that had not been adequately
      treated. Circumstances permitted this cyclone to be used as a case study to
      assess whether a simple paper-strip water-quality test (the hydrogen sulphide,
      H(2)S) kit could be distributed and used for community-based monitoring following
      such a disaster event to better protect public health. The H(2)S test results
      correlated well with faecal and total coliform results as found in previous
      studies. A small percentage of samples (about 10 per cent) tested positive for
      faecal and total coliforms but did not test positive in the H(2)S test. It was
      concluded that the H(2)S test would be well suited to wider use, especially in
      the absence of water-quality monitoring capabilities for outer island groups as
      it is inexpensive and easy to use, thus enabling communities and community health
      workers with minimal training to test their own water supplies without outside
      assistance. The importance of public education before and after natural disasters
      is also discussed.

PMID- 15569382
TI  - Conflict-related mortality: an analysis of 37 datasets.
AB  - Mortality rates are among the main indicators of the human impact of armed
      conflict and many surveys have assessed this impact both for targeting and
      evaluating humanitarian aid programmes. Almost no epidemiological analysis such
      as calculating relative risk was performed nor were reference values clearly
      described. Here the aim is to review published mortality rates for a better
      understanding of age-specific mortality in armed conflict. Published mortality
      rates from conflict situations were collected and pre-conflict reference rates
      composed. We calculated the relative risk of dying in conflict compared to pre
      conflict for children under 5 and people older than five years old. Although
      limited by reporting inadequacies, the results confirm the high vulnerability of
      children < 5 but identify a higher relative risk of dying among the > or = 5 year
      olds. Although not entirely new, this observation is not fully understood.
      Further systematic epidemiological research is needed to estimate and understand
      the impact of armed conflict on mortality.

PMID- 15569384
TI  - Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK.
AB  - BACKGROUND: Programmed cell death of motoneurons in the developing spinal cord is
      thought to be regulated through the availability of target-derived neurotrophic
      factors. When deprived of trophic support, embryonic spinal motoneurons in vitro
      over-express FasL, a ligand activating a Fas-mediated death pathway. How trophic
      factors regulate the expression of FasL is presently unclear, but two regulators
      of FasL, FOXO3a (FKHRL1) and JNK have been described to play a role in other cell
      types. Thus, their potential function in motoneurons was investigated in this
      study. RESULTS: We show here that as a result of removal of neurotrophic factors
      and the consequent reduction in signalling through the PI3K/Akt pathway, Foxo3a
      translocates from the cytoplasm to the nucleus where it triggers cell death.
      Death is reduced in Fas and FasL mutant motoneurons and in the presence of JNK
      inhibitors indicating that a significant part of it requires activation of the
      Fas/FasL pathway through JNK. CONCLUSIONS: Therefore, in motoneurons as in other
      cell types, FOXO transcriptional regulators provide an important link between
      other signalling pathways and the cell death machinery.

PMID- 15569385
TI  - Student responses to the introduction of case-based learning and practical
      activities into a theoretical obstetrics and gynaecology teaching programme.
AB  - BACKGROUND: The fourth-year Obstetrics and Gynaecology course at our institution
      had previously been taught using theory classes alone. A new teaching model was
      introduced to provide a better link with professional practice. We wished to
      evaluate the impact of the introduction of case discussions and other practical
      activities upon students' perceptions of the learning process. METHODS: Small
      group discussions of cases and practical activities were introduced for the
      teaching of a fourth-year class in 2003 (Group II; 113 students). Comparisons
      were made with the fourth-year class of 2002 (Group I; 108 students), from before
      the new programme was introduced. Students were asked to rate their satisfaction
      with various elements of the teaching programme. Statistical differences in their
      ratings were analysed using the chi-square and Bonferroni tests. RESULTS: Group
      II gave higher ratings to the clarity of theory classes and lecturers' teaching
      abilities (p < 0.05) and lecturers' punctuality (p < 0.001) than did Group I.
      Group II had greater belief that the knowledge assessment tests were useful (p <
      0.001) and that their understanding of the subject was good (p < 0.001) than did
      Group I. Group II gave a higher overall rating to the course (p < 0.05) than did
      Group I. However, there was no difference in the groups' assessments of the use
      made of the timetabled hours available for the subject or lecturers' concern for
      students' learning. CONCLUSIONS: Students were very receptive to the new teaching
      model.

PMID- 15569386
TI  - Endotracheal tube cuff pressure in three hospitals, and the volume required to
      produce an appropriate cuff pressure.
AB  - BACKGROUND: Cuff pressure in endotracheal (ET) tubes should be in the range of 20
      30 cm H2O. We tested the hypothesis that the tube cuff is inadequately inflated
      when manometers are not used. METHODS: With IRB approval, we studied 93 patients
      under general anesthesia with an ET tube in place in one teaching and two private
      hospitals. Anesthetists were blinded to study purpose. Cuff pressure in tube
      sizes 7.0 to 8.5 mm was evaluated 60 min after induction of general anesthesia
      using a manometer connected to the cuff pilot balloon. Nitrous oxide was
      disallowed. After deflating the cuff, we reinflated it in 0.5-ml increments until
      pressure was 20 cmH2O. RESULTS: Neither patient morphometrics, institution,
      experience of anesthesia provider, nor tube size influenced measured cuff
      pressure (35.3 +/- 21.6 cmH2O). Only 27% of pressures were within 20-30 cmH2O;
      27% exceeded 40 cmH2O. Although it varied considerably, the amount of air
      required to achieve a cuff pressure of 20 cmH2O was similar with each tube size.
      CONCLUSION: We recommend that ET cuff pressure be set and monitored with a
      manometer.

PMID- 15569387
TI  - Atrial fibrillation and survival in colorectal cancer.
AB  - BACKGROUND: Survival in colorectal cancer may correlate with the degree of
      systemic inflammatory response to the tumour. Atrial fibrillation may be regarded
      as an inflammatory complication. We aimed to determine if atrial fibrillation is
      a prognostic factor in colorectal cancer. PATIENTS AND METHODS: A prospective
      colorectal cancer patient database was cross-referenced with the hospital
      clinical-coding database to identify patients who had underwent colorectal cancer
      surgery and were in atrial fibrillation pre- or postoperatively. RESULTS: A total
      of 175 patients underwent surgery for colorectal cancer over a two-year period.
      Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial
      fibrillation correlated with worse two-year survival (p = 0.04; log-rank test).
      However, in a Cox regression analysis, atrial fibrillation was not significantly
      associated with survival. CONCLUSION: The presence or development of atrial
      fibrillation in patients undergoing surgery for colorectal cancer is associated
      with worse overall survival, however it was not found to be an independent factor
      in multivariate analysis.

PMID- 15569388
TI  - Noise filtering and nonparametric analysis of microarray data underscores
      discriminating markers of oral, prostate, lung, ovarian and breast cancer.
AB  - BACKGROUND: A major goal of cancer research is to identify discrete biomarkers
      that specifically characterize a given malignancy. These markers are useful in
      diagnosis, may identify potential targets for drug development, and can aid in
      evaluating treatment efficacy and predicting patient outcome. Microarray
      technology has enabled marker discovery from human cells by permitting
      measurement of steady-state mRNA levels derived from thousands of genes. However
      many challenging and unresolved issues regarding the acquisition and analysis of
      microarray data remain, such as accounting for both experimental and biological
      noise, transcripts whose expression profiles are not normally distributed,
      guidelines for statistical assessment of false positive/negative rates and
      comparing data derived from different research groups. This study addresses these
      issues using Affymetrix HG-U95A and HG-U133 GeneChip data derived from different
      research groups. RESULTS: We present here a simple non parametric approach
      coupled with noise filtering to identify sets of genes differentially expressed
      between the normal and cancer states in oral, breast, lung, prostate and ovarian
      tumors. An important feature of this study is the ability to integrate data from
      different laboratories, improving the analytical power of the individual results.
      One of the most interesting findings is the down regulation of genes involved in
      tissue differentiation. CONCLUSIONS: This study presents the development and
      application of a noise model that suppresses noise, limits false positives in the
      results, and allows integration of results from individual studies derived from
      different research groups.

PMID- 15569389
TI  - A randomized trial comparing digital and live lecture formats [ISRCTN40455708.
AB  - BACKGROUND: Medical education is increasingly being conducted in community-based
      teaching sites at diverse locations, making it difficult to provide a consistent
      curriculum. We conducted a randomized trial to assess whether students who viewed
      digital lectures would perform as well on a measure of cognitive knowledge as
      students who viewed live lectures. Students' perceptions of the digital lecture
      format and their opinion as whether a digital lecture format could serve as an
      adequate replacement for live lectures was also assessed. METHODS: Students were
      randomized to either attend a lecture series at our main campus or view digital
      versions of the same lectures at community-based teaching sites. Both groups
      completed the same examination based on the lectures, and the group viewing the
      digital lectures completed a feedback form on the digital format. RESULTS: There
      were no differences in performance as measured by means or average rank. Despite
      technical problems, the students who viewed the digital lectures overwhelmingly
      felt the digital lectures could replace live lectures. CONCLUSIONS: This study
      provides preliminary evidence digital lectures can be a viable alternative to
      live lectures as a means of delivering didactic presentations in a community
      based setting.

PMID- 15569390
TI  - Pharmacokinetics of quinacrine in the treatment of prion disease.
AB  - BACKGROUND: Prion diseases are caused by the accumulation of an aberrantly folded
      isoform of the prion protein, designated PrPSc. In a cell-based assay, quinacrine
      inhibits the conversion of normal host prion protein (PrPC) to PrPSc at a half
      maximal concentration of 300 nM. While these data suggest that quinacrine may be
      beneficial in the treatment of prion disease, its penetration into brain tissue
      has not been extensively studied. If quinacrine penetrates brain tissue in
      concentrations exceeding that demonstrated for in vitro inhibition of PrPSc, it
      may be useful in the treatment of prion disease. METHODS: Oral quinacrine at
      doses of 37.5 mg/kg/D and 75 mg/kg/D was administered to mice for 4 consecutive
      weeks. Plasma and tissue (brain, liver, spleen) samples were taken over 8 weeks:
      4 weeks with treatment, and 4 weeks after treatment ended. RESULTS: Quinacrine
      was demonstrated to penetrate rapidly into brain tissue, achieving concentrations
      up to 1500 ng/g, which is several-fold greater than that demonstrated to inhibit
      formation of PrPSc in cell culture. Particularly extensive distribution was
      observed in spleen (maximum of 100 microg/g) and liver (maximum of 400 microg/g)
      tissue. CONCLUSIONS: The documented extensive brain tissue penetration is
      encouraging suggesting quinacrine might be useful in the treatment of prion
      disease. However, further clarification of the distribution of both intracellular
      and extracellular unbound quinacrine is needed. The relative importance of free
      quinacrine in these compartments upon the conversion of normal host prion protein
      (PrPC) to PrPSc will be critical toward its potential benefit.

PMID- 15569391
TI  - Characterization of the chicken inward rectifier K+ channel IRK1/Kir2.1 gene.
AB  - BACKGROUND: Inward rectifier potassium channels (IRK) contribute to the normal
      function of skeletal and cardiac muscle cells. The chick inward rectifier K+
      channel cIRK1/Kir2.1 is expressed in skeletal muscle, heart, brain, but not in
      liver; a distribution similar but not identical to that of mouse Kir2.1. We set
      out to explore regulatory domains of the cIRK1 promoter that enhance or inhibit
      expression of the gene in different cell types. RESULTS: We cloned and
      characterized the 5'-flanking region of cIRK1. cIRK1 contains two exons with
      splice sites in the 5'-untranslated region, a structure similar to mouse and
      human orthologs. cIRK1 has multiple transcription initiation sites, a feature
      also seen in mouse. However, while the chicken and mouse promoter regions share
      many regulatory motifs, cIRK1 possesses a GC-richer promoter and a putative TATA
      box, which appears to positively regulate gene expression. We report here the
      identification of several candidate cell/tissue specific cIRK1 regulatory domains
      by comparing promoter activities in expressing (Qm7) and non-expressing (DF1)
      cells using in vitro transcription assays. CONCLUSION: While multiple
      transcription initiation sites and the combinatorial function of several domains
      in activating cIRK1 expression are similar to those seen in mKir2.1, the cIRK1
      promoter differs by the presence of a putative TATA box. In addition, several
      domains that regulate the gene's expression differentially in muscle (Qm7) and
      fibroblast cells (DF1) were identified. These results provide fundamental data to
      analyze cIRK1 transcriptional mechanisms. The control elements identified here
      may provide clues to the tissue-specific expression of this K+ channel.

PMID- 15569392
TI  - The hazards of lack of co-registration of ictal brain SPECT with MRI: A case
      report of sinusitis mimicking a brainstem seizure focus.
AB  - BACKGROUND: Single photon emission computed tomography (SPECT) following
      injection of radiotracer during a seizure is known as ictal SPECT. Comparison of
      an ictal SPECT study to a baseline or interictal study can aid identification of
      a seizure focus. CASE PRESENTATION: A young woman with encephalitis and
      refractory seizures underwent brain SPECT during a period of frequent seizure
      like episodes, and during a seizure-free period. A focal area of increased
      radiotracer uptake present only when she was experiencing frequent seizure-like
      episodes was originally localized to the brainstem, but with later computerized
      co-registration of SPECT to MRI, was found to lie outside the brain, in the
      region of the sphenoid sinus. CONCLUSION: Low-resolution SPECT images present
      difficulties in interpretation, which can be overcome through co-registration to
      higher-resolution structural images.

PMID- 15569393
TI  - Regional risks and seasonality in travel-associated campylobacteriosis.
AB  - BACKGROUND: The epidemiology of travel-associated campylobacteriosis is still
      largely unclear, and various known risk factors could only explain limited
      proportions of the recorded cases. METHODS: Using data from 28,704 notifications
      of travel-associated campylobacteriosis in Sweden 1997 to 2003 and travel
      patterns of 16,255 Swedish residents with overnight travel abroad in the same
      years, we analysed risks for travel-associated campylobacteriosis in 19 regions
      of the world, and looked into the seasonality of the disease in each of these
      regions. RESULTS: The highest risk was seen in returning travellers from the
      Indian subcontinent (1,253/100,000 travellers), and the lowest in travellers from
      the other Nordic countries (3/100,000 travellers). In Africa, large differences
      in risk between regions were noted, with 502 /100,000 in travellers from East
      Africa, compared to 76/100,00 from West Africa and 50/100,000 from Central
      Africa. A distinct seasonal pattern was seen in all temperate regions with peaks
      in the summer, while no or less distinct seasonality was seen in tropical
      regions. In travellers to the tropics, the highest risk was seen in children
      below the age of six. CONCLUSIONS: Data on infections in returning travellers
      together with good denominator data could provide comparable data on travel risks
      in various regions of the world.

PMID- 15569394
TI  - Reduced bio-efficacy of permethrin EC impregnated bednets against an Anopheles
      gambiae strain with oxidase-based pyrethroid tolerance.
AB  - BACKGROUND: Insecticide-treated nets (ITNs) are an integral component of malaria
      control programmes in Africa. How much pyrethroid resistance in malaria vectors
      will impact on the efficacy of ITNs is controversial. The purpose of this study
      was to evaluate knockdown and killing effects of ITNs on a metabolic-based
      resistant or tolerant malaria vector strain. METHODS: Bio-efficacy of 500 mg/m2
      permethrin EC treated bednets was assessed on the OCEAC laboratory (OC-Lab)
      strain of Anopheles gambiae s.s.. This strain is resistant to DDT and tolerant to
      pyrethroids, with elevated mixed function oxidases. The Kisumu reference
      susceptible strain of A. gambiae s.s. was used as control. Nets were impregnated
      in February 1998 and used by households of the Ebogo village. Then they were
      collected monthly over six months for Bio-assays (WHO cone test). Knockdown and
      mortality rates were compared between the OC-Lab and the Kisumu strains, by means
      of the Mantel-Haenszel chi-square test. RESULTS: During the whole trial,
      permethrin EC knockdown rates were impressive (mostly higher than 97%). No
      significant difference was observed between the two strains. However, the
      mortality rates were significantly decreased in the OC-Lab strain (40-80%)
      compared with that of the Kisumu strain (75-100%). The decrease of killing effect
      on the OC-Lab strain was attributed to permethrin EC tolerance, due to the high
      oxidase metabolic activity. CONCLUSION: These data suggested an impact of
      pyrethroid tolerance on the residual activity of ITNs. More attention should be
      given to early detection of resistance using biochemical or molecular assays for
      better resistance management.

PMID- 15569395
TI  - Leniency and halo effects in marking undergraduate short research projects.
AB  - BACKGROUND: Supervisors are often involved in the assessment of projects they
      have supervised themselves. Previous research suggests that detailed marking
      sheets may alleviate leniency and halo effects. We set out to determine if,
      despite using such a marking schedule, leniency and halo effects were evident in
      the supervisors' marking of undergraduate short research projects (special study
      modules (SSM)). METHODS: Review of grades awarded by supervisors, second markers
      and control markers to the written reports of 4th year medical students who had
      participated in an SSM during two full academic years (n = 399). Paired t-tests
      were used to compare mean marks, Pearson correlation to look at agreement between
      marks and multiple linear regression to test the prediction of one mark from
      several others adjusted for one another. RESULTS: There was a highly significant
      difference of approximately half a grade between supervisors and second markers
      with supervisors marking higher. (t = 3.12, p < 0.01, difference in grade score =
      0.42, 95% CI for mean difference 0.18-0.80). There was a high correlation between
      the two marks awarded for performance of the project and the written report by
      the supervisor (r = 0.75), but a low-modest correlation between supervisor and
      second marker (r = 0.28). Linear regression analysis of the influence of the
      supervisors' mark for performance on their mark for the report gave a non
      significant result. This suggests a leniency effect but no halo effect.
      CONCLUSIONS: This study shows that with the use of structured marking sheet for
      assessment of undergraduate medical students, supervisors marks are not
      associated with a halo effect, but leniency does occur. As supervisor assessment
      is becoming more common in both under graduate and postgraduate teaching new ways
      to improve objectivity in marking and to address the leniency of supervisors
      should be sought.

PMID- 15569396
TI  - Retinoids: potential in cancer prevention and therapy.
AB  - Retinoids (derivatives of vitamin A) are signalling molecules that play important
      roles in cell growth, differentiation and death. Retinoids act through two types
      of receptors - retinoic acid receptors (RAR alpha, RAR beta and RAR gamma) and
      retinoid X receptors (RXR alpha, RXR beta and RXR gamma) - which themselves act
      as ligand-dependent transcription factors. Retinoids are of special interest in
      cancer research owing to their antiproliferative and cancer-preventative
      properties. They have been used successfully to cure acute promyelocytic
      leukaemia (APL) and can suppress carcinogenesis in a variety of tissue types
      (e.g. skin, lung, breast and oral cancers). Extensive research efforts have been
      dedicated to elucidating the molecular and cellular networks that are induced by
      retinoids, and this has recently yielded novel insights into how retinoids can
      both prevent and combat cancer.

PMID- 15569397
TI  - Antidepressant effects of different schedules of repetitive transcranial magnetic
      stimulation vs. clomipramine in patients with major depression: relationship to
      changes in cortical excitability.
AB  - The antidepressant effects of repetitive transcranial magnetic stimulation (rTMS)
      that have been demonstrated in recent studies could be related to its ability to
      modulate cortical excitability. Yet, the relationship between stimulus location
      and frequency and treatment outcome has not been established. The aim of the
      present study was to compare efficacy of rTMS in various configurations and
      clomipramine treatment in patients with major depression (MD) and to evaluate the
      relationship between clinical outcome and changes in cortical excitability. Fifty
      nine MD patients were randomized to receive (1) left (n = 12) or right (n = 12) 3
      Hz rTMS with placebo medication; (2) left (n = 10) or right (n = 9) 10 Hz rTMS
      with placebo medication; (3) active medication (clomipramine) with sham rTMS (n =
      16). Both 3 Hz and 10 Hz rTMS were administered to the prefrontal cortex by a
      circular coil at an intensity of 110% and 100% of the resting motor threshold
      (rMT) respectively. Measurements of cortical excitability were performed prior to
      and 24 h after completion of 2 wk of daily rTMS or pharmacological treatments.
      These included the rMT, silent period threshold (SPT), inter-threshold difference
      (ITD), MEP/M-wave amplitude ratio and silent period duration (SPD). Severity of
      depression was blindly assessed by the Hamilton Depression Rating Scale (HDRS).
      The best improvement scores were seen in patients who received left 3 Hz rTMS.
      The 10 Hz rTMS treatment was less tolerated resulting in a significantly higher
      dropout rate. A significant increase of the MEP/M wave amplitude ratio
      accompanied by a shortening of the SPD was evidenced in patients who showed
      marked clinical improvement (reduction in HDRS by 50% or more) following left
      rTMS regardless of stimulation frequency. Our results suggest that 3 Hz left rTMS
      has a higher therapeutic efficacy and tolerability in patients with MD. The
      enhancement of cortical excitability may be related to the antidepressant action
      of rTMS.

PMID- 15569398
TI  - Treatment of Raynaud's phenomenon with escitalopram.

PMID- 15569399
TI  - Troponin I, cardiac diastolic dysfunction and restrictive cardiomyopathy.
AB  - Cardiomyopathies are diseases of heart muscle that are associated with cardiac
      dysfunction. Molecular genetic studies performed to date have demonstrated that
      the damage or mutations in several sarcomeric contractile protein genes are
      associated with the development of the diseases. In this review, cardiac troponin
      I, one of the sarcomeric thin filament protein, will be discussed regarding its
      role in cardiac function, its deficiency-related diastolic dysfunction, and the
      mutation of this protein-mediated restrictive cardiomyopathy.

PMID- 15569400
TI  - Population pharmacokinetic model of valproate and prediction of valproate serum
      concentrations in children with epilepsy.
AB  - AIM: Using sparse data of valproate (VPA) serum concentrations to build a
      population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy
      and to predict serum concentrations for new patients using a Bayesian approach.
      METHODS: Two hundred epileptic children, whose VPA serum concentrations were
      collected, were divided randomly into two groups (A and B, n=100 each). The PPK
      parameter values of group A were calculated to establish a PPK Model by using the
      NPEM Program of USC*PACK software. Based on it, VPA serum concentrations of group
      B were predicted with the Bayesian Fitting Program of the USC*PACK software. To
      assess the accuracy and precision of prediction, a paired-comparisons t-test was
      run between predicted and observed concentrations, and then the mean prediction
      error (MPE), mean square prediction error (MSPE), root mean square prediction
      error (RMSPE), and coincidence rates for different percentages of prediction
      error were all calculated. RESULTS: Optimum PPK parameters were: Ka, 2.522+/
      2.743 h(-1); Vs, 0.329+/-0.496 L/kg; and Kel, 0.0438+/-0.0384 h(-1). For group B,
      there was no significant difference between predicted and observed
      concentrations. MPE was -0.43 mg/L, MSPE was 115.40 (mg/L)2, and RMSPE was 5.47
      mg/L. The coincidence rates for percentages of prediction error, which were less
      than 5 %, 10 %, 15 %, 20 %, 25 %, and 30 %, were 62 %, 74 %, 82 %, 85 %, 89 %,
      and 93 %, respectively. CONCLUSION: A PPK model of VPA in epileptic children was
      successfully established. Based on it, VPA serum concentrations can be predicted
      accurately with a Bayesian approach.

PMID- 15569401
TI  - Determination of gemcitabine and its metabolite in human plasma using high
      pressure liquid chromatography coupled with a diode array detector.
AB  - AIM: To establish a high-pressure liquid chromatography (HPLC) method for
      determination of the concentration of gemcitabine (dFdC) and its metabolite
      (dFdU) in human plasma. METHODS: Plasma 1.0 mL spiked with floxuridine as an
      internal standard was extracted with 3.0 mL of methanol-acetonitrile (v/v, 1:9).
      The supernatant was evaporated at 60 centigrade and the residue was reconstituted
      with 0.5 mL of the solution used as the mobile phase. After centrifugation, 50
      microL of the supernatant was injected into the HPLC system. Separation was
      achieved on a C18 (4.6 mm multiply 50 mm, 5 microm) column at 25 centigrade with
      the flow rate of the mobile phase set to 0.8 mL/min. The compounds were detected
      at 268 nm. The mobile phase consisted of 40.0 mmol/L acetate ammonium buffer
      solution (pH 5.5) and acetonitrile (v/v, 97.5:2.5). RESULTS: The linear range was
      0.20-10.0 mg/L (r=0.9999) for dFdC and 0.50-50.0 mg/L (r=0.9999) for dFdU. The
      limit of detection (LOD) was 0.10 mg/L for dFdC and 0.25 mg/L for dFdU, while the
      limit of quantification (LOQ) was 0.20 mg/L (RSD<10 %) for dFdC and 0.50 mg/L
      (RSD<3 %) for dFdU. The average recovery of dFdC and dFdU by this method were
      103.3 % and 98.7 %, respectively. For intra-day and inter-day, the corresponding
      standard deviations of the measurements of dFdC and dFdU were both less than 5.5
      %. CONCLUSION: An analytical method was established to measure the concentrations
      of dFdC and dFdU in human plasma and was effectively applied to the dFdC and dFdU
      pharmacokinetic studies of 8 Chinese patients with malignant tumors.

PMID- 15569402
TI  - Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and
      neuronal degeneration in rats.
AB  - AIM: To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic
      cerebral hypoperfusion induced deficits in rats. METHODS: Chronic hypoperfusion
      in rats was performed by permanent bilateral ligation of the common carotid
      arteries. Morris water maze was used to measure spatial memory performance.
      Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA
      content, TXB2, and 6-keto-PGF1alpha levels. Morphological change was examined by
      HE staining. The expression of Bax and p53 protein were assayed by
      immunohistochemistry analysis. RESULTS: Chronic hypoperfusion in rats resulted in
      spatial memory impairments shown by longer escape latency and shorter time spent
      in the target quadrant. These behavioral dysfunction were accompanied by increase
      in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory
      mediators (TXB2, 6-keto-PGF1alpha), overexpression of Bax and P53 protein, and
      delayed degeneration of neurons in cortex and hippocampus. Oral administration of
      CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment,
      reduced the increase in antioxidant enzyme activities, MDA content and the levels
      of pro-inflammatory mediators to their normal levels, and attenuated neuronal
      damage. CONCLUSION: The abilities of CPH to attenuate memory deficits and
      neuronal damage after ischemia may be beneficial in cerebrovascular type
      dementia.

PMID- 15569403
TI  - Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its
      correlation with DA receptor subtypes.
AB  - AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine)
      possesses the D1 agonist-D2 antagonist action on meso-accumbens-mPFC DA system.
      METHODS: Single unit spontaneous firing activity was recorded in the nucleus
      accumbens (NAc) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)
      lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or
      iontophoretically were determined by the change of firing rates. RESULTS: Under
      normal conditions, the systemic administration of THPB-18 produced a decrease
      increase biphasic firing pattern in the NAc neurons during cumulative doses. High
      dose of THPB-18 was capable of reversing the inhibition induced by both D2
      agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone
      pretreatment could not block the high dose of THPB-18-induced firing rate
      increase, which was reversed by the D1 selective antagonist SCH23390. The tested
      NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90
      % of 6-OHDA-lesioned rats, while THPB-18 caused variable effects on the firing of
      NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18
      was blocked by iontophoretic application of SCH23390, but not D2 antagonist
      spiperone. CONCLUSION: Similar to L-stepholidine, THPB-18 also possesses the D1
      agonistic-D2 antagonistic dual action on the VTA-NAc DA system.

PMID- 15569404
TI  - Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in
      cortical neurons.
AB  - AIM: To investigate the effect of curcumin on tert-butyl hydroperoxide (t-BHP)
      induced oxidative damage in rat cortical neurons and to explore the possible
      mechanism. METHODS: Primary cultured rat cortical neurons were performed in vitro
      and cell viability was measured by MTT assay. DNA fragmentation was used to
      evaluate cell apoptosis. Intracellular reactive oxygen species (ROS) and
      mitochondrial membrane potential (Deltapsim) was determined by flow cytometric
      assay. Cellular glutathione (GSH) content was measured by spectrophotometer. Bcl
      2 family proteins, cytochrome c, cleaved caspase-3, and poly (ADP-ribose)
      polymerase (PARP) were detected by Western blot. RESULTS: Exposure of tBHP 100
      micromol/L to neurons for 60 min resulted in DYm loss and cytochrome c release
      from mitochondria and subsequent activation of caspase-3 and PARP cleavation, and
      cell apoptosis. After removal of tBHP and then further treatment with curcumin
      (2.5-20 micromol/L) for 18 h, curcumin abrogated Deltapsim loss and cytochrome c
      release, blocked activation of caspase 3, and altered the expression of Bcl-2
      family. Further curcumin treatment also prevented cellular GSH and decreased
      intracellular ROS generation markedly. Curcumin eventually attenuated tBHP
      induced apoptosis in cortical neurons. CONCLUSION: Curcumin may attenuate
      oxidative damages in cortical neurons by reducing intracellular production of ROS
      and protecting mitochondria from oxidative damage.

PMID- 15569405
TI  - Down-regulation amyloid beta-protein 42 production by interfering with transcript
      of presenilin 1 gene with siRNA.
AB  - AIM: To investigate the pathogenesis of Abeta42 yielding and new drug targets as
      well as the possibility of RNA interference (RNAi) technique for treatment of
      Alzheimer disease (AD). METHODS: Human AD presenilin 1 (PS1) cDNA sequence was
      obtained from NCBI website. The three sites of RNAi action and one missense
      control site were selected in PS1 cDNA through online design of Ambion company.
      To confirm specificity of these sites, we conducted a BLAST search of the IMAGE
      EST library. The corresponding double-stranded DNA was used to construct
      pSilencer 3.1-H1 plasmid, which could transcribe small interference RNA (siRNA).
      Then, the pSliencer 3.1-H1 plasmids were transfected into CHO/PS1/APP cells with
      SuperFect transfection reagent. The cells have been transfected with the mutant
      PS1 and APP gene of AD. All the CHO/PS1/APP cells with pSliencer 3.1-H1 plasmids
      were screened out using G418. Transcripts of PS1 gene in CHO/PS1/APP were
      measured by RT-PCR, the contents of PS1 peptide and Abeta42 production inside
      CHO/PS1/APP cells were examined through Western blot and the Abeta42 change of
      secretion by CHO/PS1/APP was determined with ELISA. RESULTS: The site 3 of PS1
      mRNA was inhibited by RNAi after 2 d. The effect was more obvious with the time.
      The peptide corresponding to PS1 gene and Abeta42 production in CHO/PS1/APP cells
      were both reduced after siRNA interfere for 3 d. Abeta42 secretion by CHO/PS1/APP
      cells began to reduce on d 3, and reached the most significance on d 5. There was
      a time-dependent relationship between the transcript of PS1 gene and the
      production of Abeta42 with RNAi action. CONCLUSION: PS1 is essential for g
      secretase activity. Inhibition of the PS1 can decrease the levels of Abeta42.
      Some sites of PS1 mRNA, for example, the site 3, may serve as a new drug target
      and RNAi probably can be used for treatment of AD.

PMID- 15569406
TI  - GABAA receptor partially mediated propofol-induced hyperalgesia at superspinal
      level and analgesia at spinal cord level in rats.
AB  - AIM: To observe effects of propofol on nociceptive response at superspinal and
      spinal level in rats. METHODS: Two hundreds and fifty-eight Sprague-Dawley male
      rats were randomized into thirty-two groups. Propofol and bicuculline were
      microinjected into lateral ventricle (icv), ventrolateral periaqueductal gray
      (vlPAG), intrathecal (ith), and intraperitoneal (ip). The noxious responses were
      evaluated by hot plate and formalin test. RESULTS: In hot-plate test, systemic
      and superspinal administration of propofol (40 mg.kg(-1) ip, 100 microg in 10
      microL, icv, and 4 microg in 0.4 microL vlPAG microinjection) produced
      hyperalgesia (P<0.01). Hyperalgesia induced by vlPAG microinjection of propofol
      was significantly antagonized by 69.8 %, 71.2 %, 98.8 % at 10, 20, and 30 min by
      microinjection of bicuculline (10 ng in 0.4 microL, vlPAG) (P<0.01). Analgesia
      induced by ith propofol (100 microg.10 microL(-1)) was antagonized about 81.3 %,
      54.8 %, 80.8 %, and 97.4 % at 10, 20, 30 and 40 min by ith bicuculline (P<0.05).
      In formalin test, systemic and superspinal administration of propofol (40 mg.kg(
      1) ip, 4 microg in 0.4 microL, vlPAG) also produced hyperalgesia (P<0.01). The
      increased formalin pain scores were antagonized about 57.1 % by bicuculline (10
      ng, vlPAG) (P<0.05) at 60 min after formalin injection. The decreased formalin
      pain scores induced by ith propofol (100 microg in 10 microL) were antagonized
      about 66.7 % at 30 min by ith bicuculline (P<0.05) after formalin injection.
      Hyperalgesia produced by ip propofol in both hot plate and formalin test could
      not be antagonized by vlPAG administration of bicuculline. CONCLUSION: GABAA
      receptor partly mediated propofol-induced hyperalgesia at superspinal and
      analgesia at spinal cord in rats.

PMID- 15569407
TI  - Increased salt sensitivity induced by sensory denervation: role of superoxide.
AB  - AIM: To test the hypothesis that production of superoxide in mesenteric
      resistance arteries is increased and contributes to the development of
      hypertension induced by sensory denervation plus high salt intake. METHODS:
      Newborn Wistar rats were given capsaicin 50 mg/kg sc on the 1st and 2nd d of
      life. After weaning, male rats were grouped as follows and treated for 3 weeks
      with: capsaicin pretreatment plus normal sodium diet (0.5 %, CAP-NS), CAP plus
      high sodium diet (4 %, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail
      cuff systolic blood pressure and mean arterial pressure (MAP) were measured in
      each of the groups. Western blot analysis was used for measurement of manganese
      superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the
      mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for
      superoxide production in the mesenteric resistance arteries. The Griess method
      was used for measurement of nitrite/nitrate levels in plasma. RESULTS: Both tail
      cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON
      NS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were
      increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However,
      nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv
      administration of tempol, a membrane-permeable superoxide scavenger, decreased
      MAP in both CAP-HS and CON-HS when compared with their respective controls.
      However, the decreases of MAP between these two groups were not different.
      Chronic treatment with tempol failed to prevent the development of hypertension
      in CAP-HS rats. Superoxide production in the mesenteric resistance arteries was
      increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However,
      chronic treatment with tempol did not prevent the increase of mesenteric
      superoxide production in CAP-HS rats. CONCLUSIONS: Regardless of increased
      vascular MnSOD levels, salt sensitive hypertension induced by sensory
      degeneration is associated with increased vascular superoxide production.
      Although tempol is incapable of preventing the development of hypertension in
      sensory denervated rats fed a high salt diet, increased superoxide levels may
      contribute to exacerbated vascular impairment which may take longer time to
      develop. Given that superoxide may be produced by sources other than
      mitochondrion, future studies using other inhibitors (eg, inhibitors of NADPH
      oxidase and xanthine oxidase) may unveil the effectiveness of reducing superoxide
      on lowering blood pressure in this model.

PMID- 15569408
TI  - Aspirin protected against endothelial damage induced by LDL: role of endogenous
      NO synthase inhibitors in rats.
AB  - AIM: To study the protective effect of aspirin on damages of the endothelium
      induced by low-density lipoprotein (LDL), and whether the protective effect of
      aspirin is related to reduction of nitric oxide synthase inhibitor level.
      METHODS: Vascular endothelial injury was induced by a single injection of native
      LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (ACh) in the
      isolated aortic rings were determined, and serum concentrations of asymmetric
      dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF
      alpha), and the activity of dimethylaminohydrolase (DDAH) were measured. RESULTS:
      A single injection of LDL (4 mg/kg) significantly decreased vasodilator responses
      to ACh, increased the serum level of ADMA, MDA, and TNF-alpha, and decreased DDAH
      activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of
      vasodilator responses to ACh by LDL, and the protective effect of aspirin at the
      lower dose was greater compared with high-dose aspirin group. Aspirin inhibited
      the increased level of MDA and TNF-alpha induced by LDL. Aspirin at the dose of
      30 mg/kg, but not at higher dose (100 mg/kg), significantly reduced the
      concentration of ADMA and increased the activity of DDAH. CONCLUSION: Aspirin at
      the lower dose (30 mg/kg) protects the endothelium against damages elicited by
      LDL in vivo, and the protective effect of aspirin on endothelium is related to
      reduction of ADMA concentration by increasing DDAH activity.

PMID- 15569409
TI  - Rilmenidine prevents blood pressure increase in rats with compromised nitric
      oxide production.
AB  - AIM: To search tools of high blood pressure in the model of nitric oxide (NO)
      defective hypertension, and the study focused on the effect of rilmenidine,
      agonist of imidazoline receptors, which was suggested to modulate central
      sympathetic outflow. METHODS: Three experimental groups, each consisting of 7
      rats, were used: (I) rats with inhibition of NO synthase (NOS) by N(G)-nitro-L
      arginine methyl ester (L-NAME) 40 mg.kg(-1).d(-1) for 4 weeks in drinking water,
      (II) rats with inhibited NOS as in group I , plus agonist of imidazoline
      receptors rilmenidine 3 mg.kg(-1).d(-1) for 4 weeks by gavage, and (III) control
      rats. Systolic blood pressure was measured weekly noninvasively. At the end of
      experiment aortic ring isometric tension was followed, NOS expression (aorta,
      left ventricle), and NOS activity (left ventricle and brain) were determined.
      RESULTS: In the group I systolic blood pressure increased significantly, aortic
      ring relaxation to acetylcholine was significantly attenuated. Rilmenidine
      administered simultaneously with L-NAME (group II) prevented the increase of
      blood pressure which did not differ significantly from control values; aortic
      ring relaxation to acetylcholine did not differ from control. No change in NOS
      expression (aorta and left ventricle) was found in groups I and II. Significant
      decline in NOS activity (left ventricle and brain) was found in groups I and II.
      CONCLUSION: Rilmenidine has a remarkable role in NO-defective hypertension,
      possibly by inhibiting central sympathetic outflow and by affecting receptors in
      vascular smooth muscle also. The prime cause of hypertension in this experimental
      model--the compromised production of NO due to inhibition of NOS--was not
      affected by rilmenidine.

PMID- 15569410
TI  - Effect of Zn2+ ions on ryanodine binding to sarcoplasmic reticulum of striated
      muscles in the presence of pyrithione.
AB  - AIM: To explore whether the differential effects of Zn2+ on ryanodine binding to
      the sarcoplasmic reticulum (SR) of skeletal and cardiac muscles resulted from
      different permeability of the SR to Zn2+. METHODS: [3H]ryanodine binding assays
      were performed to examine the effect of Zn2+ on ryanodine binding to the SR in
      the presence of pyrithione sodium (PyNa), a specific Zn2+ ionophore. RESULTS: As
      a control, PyNa up to 50 micromol/L did not induce any effect on ryanodine
      binding to the SR of cardiac muscle. But PyNa 1-100 micromol/L increased
      ryanodine binding in skeletal muscle with maximum binding (222.2+/-20.9 % of the
      control) and inhibited ryanodine binding to 50 % of the control at about 500
      micromol/L. In the presence of PyNa 10 and 50 micromol/L the dose-dependence of
      the effect of Zn2+ in cardiac muscle was still monophasic and not changed by
      PyNa, while the biphasic effect of Zn2+ in skeletal muscle became monophasic.
      CONCLUSION: Different permeability of the SR to Zn2+ may account for the
      differential effects of Zn2+ on ryanodine binding in skeletal and cardiac
      muscles. PyNa is not a strictly specific Zn2+ ionophore.

PMID- 15569411
TI  - Effect of vasoactive intestinal peptide on pulmonary surfactants phospholipid
      synthesis in lung explants.
AB  - AIM: To investigate the effect of vasoactive intestinal peptide (VIP) on
      pulmonary surfactants (PS) phospholipid synthesis in cultured lung explants.
      METHODS: Lung explants were cultured with serum-free medium, [methyl-3H]choline
      incorporation, total phospholipid, phosphatidylcholine, activity of choline
      phosphate cytidylyltransferase (CCT) and CCTalpha mRNA level in lung explants
      were determined. RESULTS: (1) VIP (10(-10)-10(-7) mol/L) for 16 h promoted
      [methyl-3H]choline incorporation in dose dependence and VIP (10(-8) mol/L) for 2
      h-16 h promoted [methyl-3H]choline incorporation in time dependence. (2) VIP (10(
      8) mol/L) enhanced the contents of total phospholipids and phosphatidylcholine in
      lung explants. (3) VIP (10(-10)-10(-7) mol/L) elevated microsomal CCT activity of
      lung explants in dose dependence. (4) VIP (10(-8) mol/L) increased expression of
      CCTalpha mRNA in lung explants and alveolar type II cells (ATII). (5) [D-P-Cl
      Phe(6)-Leu(17)]-VIP (10(-6) mol/L), a VIP receptors antagonist, abolished the
      increase of [3H]choline incorporation, microsomal CCT activity and CCTalpha mRNA
      level induced by VIP (10(-8) mol/L) in lung explants. CONCLUSION: VIP could
      enhance synthesis of phosphatidylcholine, the major component of pulmonary
      surfactants by enhancing microsomal CCT activity and CCTalpha mRNA level via VIP
      receptor-mediated pathway.

PMID- 15569412
TI  - Establishment of liver specific glucokinase gene knockout mice: a new animal
      model for screening anti-diabetic drugs.
AB  - AIM: To characterize the liver-specific role of glucokinase in maintaining
      glucose homeostasis and to create an animal model for diabetes. METHODS: We
      performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP
      gene targeting strategy. First, two directly repeated loxP sequences were
      inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To
      achieve this, linearized targeting vector was electroporated into ES cells. Then
      G418- and Gancyclovir-double-resistant clones were picked and screened by PCR
      analysis and the positives identified by PCR were confirmed by Southern blot. A
      targeted clone was selected for microinjection into C57BL/6J blastocysts and
      implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring
      were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice
      with mice containing a conditional gk allele, we obtained mice with liver
      specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4
      were positive to PCR and Southern blot and only one was used for further
      experiments. Eventually we generated the liver specific glucokinase knockout
      mice. These mice showed increased glucose level with age and at the age of 6
      weeks fasting blood glucose level was significantly higher than control and they
      also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that
      hepatic glucokinase plays an important role in glucose homeostasis and its
      deficiencies contribute to the development of diabetes. The liver glucokinase
      knockout mouse is an ideal animal model for MODY2, and it also can be applied for
      screening anti-diabetic drugs.

PMID- 15569413
TI  - Interleukin-12 was not involved in promotion of T helper cell differentiation
      induced by theophylline.
AB  - AIM: To investigate the effect of theophylline on the naive T cell
      differentiation and the probable role of interleukin-12 (IL-12). METHODS: Naive
      cord blood T cells were treated with theophylline 10 mg/L for 3 d after
      stimulation with PHA 100 mg/L. Differentiation of T cells was analyzed by flow
      cytometry. Theophylline 10 mg/L and IL-12-mAb 0.025 mg/L were added in cord blood
      mononuclear cell (CBMC) cultures primed with LPS 1 mg/L to detect the levels of
      IL-12 and IL-12P40. The whole blood cultures were obtained from twelve health
      volunteers with or without administration of theophylline (200 mg). Cytokines
      were measured by enzyme linked immuno-sorbent assay. RESULTS: Theophylline
      promoted T helper 1 (Th1) cells differentiation from naive T cells (21.9 %+/-10.3
      % vs 9.4 %+/-5.6 %, P<0.05), but had no significant effect on Th2 deviation. But
      theophylline inhibited the production of IL-12 and IL-12P40 by CBMC in vitro
      (28+/-6 ng/L vs 57+/-14 ng/L and 88+/-34 ng/L vs 214+/-82 ng/L, P<0.01) and
      reduced IL-12 and IL-12P40 levels in whole blood cultures from healthy subjects
      (19+/-11 ng/L vs 31+/-15 ng/L and 92+/-13 ng/L vs 196+/-49 ng/L, P<0.01).
      CONCLUSION: Theophylline promoted the differentiation of Th1 cells. IL-12 seemed
      not to be involved in this process.

PMID- 15569414
TI  - Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen
      cells.
AB  - AIM: To investigate the immunoenhancing activity of ginsenoside-F3 in murine
      spleen cells and explore its mechanism. METHODS: The enhancing effect of
      ginsenoside-F3 on murine spleen cell proliferation was studied using
      [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of
      type 1 cytokines IL-2, IFN-gamma, and type 2 cytokines IL-4 and IL-10 from murine
      spleen cells were detected by ELISA method. Effects of ginsenoside-F3 on mRNA
      level of cytokines IL-4, IFN-gamma, and transcription factors T-bet and GATA-3
      were evaluated by RT-PCR analysis. Effect of ginsenoside-F3 on NF-kappaB DNA
      binding activity in murine spleen cells was investigated by electrophoretic
      mobility shift assays (EMSA). RESULTS: Ginsenoside-F3 at 0.1-100 micromol/L not
      only promoted the murine spleen cell proliferation, but also increased the
      production of IL-2 and IFN-gamma, while decreased the production of IL-4 and IL
      10 from murine spleen cells with the maximal effect at 10 micromol/L. RT-PCR
      analysis displayed that ginsenoside-F3 enhanced the IFN-gamma and T-bet gene
      expression and decreased IL-4 and GATA-3 gene expression. EMSA experiment showed
      that ginsenoside-F3 10 micromol/L enhanced the NF-kappaB DNA binding activity
      induced by ConA in murine spleen cells. CONCLUSION: Ginsenoside-F3 has
      immunoenhancing activity by regulating production and gene expression of type 1
      cytokines and type 2 cytokines in murine spleen cells.

PMID- 15569415
TI  - Inhibition of tryptase and chymase induced nucleated cell infiltration by
      proteinase inhibitors.
AB  - AIM: To investigate the ability of proteinase inhibitors to modulate nucleated
      cell infiltration into the peritoneum of mice induced by tryptase and chymase.
      METHODS: Human lung tryptase and skin chymase were purified by a similar
      procedure involving high salt extraction, heparin agarose affinity chromatography
      followed by S-200 Sephacryl gel filtration chromatography. The actions of
      proteinase inhibitors on tryptase and chymase induced nucleated cell accumulation
      were examined with a mouse peritoneum model. RESULTS: A selective chymase
      inhibitor Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPPF) was able to inhibit approximately 90 %
      neutrophil, 73 % eosinophil, 87 % lymphocyte and 60 % macrophage accumulation
      induced by chymase at 16 h following injection. Soy bean trypsin inhibitor
      (SBTI), chymostatin, and alpha1-antitrypsin showed slightly less potency than
      ZIGPPF in inhibition of the actions of chymase. While all tryptase inhibitors
      tested were able to inhibit neutrophil, eosinophil, and macrophage accumulation
      provoked by tryptase at 16 h following injection, only leupeptin, APC366, and
      aprotinin were capable of inhibiting tryptase induced lymphocyte accumulation.
      The inhibitors of tryptase tested were also able to inhibit tryptase induced
      neutrophil and eosinophil accumulation at 6 h following injection. When being
      injected alone, all inhibitors of chymase and tryptase at the concentrations
      tested by themselves had no significant effect on the accumulation of nucleated
      cells in the peritoneum of mice at both 6 h and 16 h. CONCLUSION: Proteinase
      inhibitors significantly inhibited tryptase and chymase-induced nucleated cell
      accumulation in vivo, and therefore they are likely to be developed as a novel
      class of anti-inflammatory drugs.

PMID- 15569416
TI  - Effects of chlorogenic acid, an active compound activating calcineurin, purified
      from Flos Lonicerae on macrophage.
AB  - AIM: To investigate the activation of chlorogenic acid (CHA) purified from Flos
      Lonicerae to calcineurin and its effects on macrophage functions in vivo and in
      vitro. METHODS: According to the screening results that Flos Lonicerae could
      activate calcineurin, the active component which could activate calcineurin was
      purified from Flos Lonicerae by column chromatography on silica gel and
      identified as CHA. The activation of CHA on calcineurin had been validated with
      both p-NPP and 32P-labeled RII peptide as the substrates. The clearance of
      charcoal particles in normal mice and the cytotoxicity of U937 to MCF-7 were used
      together to determine the effects of CHA on macrophage functions. RESULTS: CHA
      could activate calcineurin, and the concentration of CHA on maximal activating
      calcineurin was 282.5 micromol/L. CHA administration (10 mg/kg, ig, 7 d)
      significantly enhanced the macrophage functions in normal mice. CHA (70.6, 141.2,
      and 282.5 micromol/L) obviously increased the cytotoxicity of U937 to MCF-7.
      CONCLUSION: CHA could activate calcineurin and enhance the macrophage functions
      in vivo and in vitro, and its functions in vivo may be realized via the signal
      pathways of calcineurin.

PMID- 15569417
TI  - Association of estrogen receptor-alpha and vitamin D receptor genotypes with
      therapeutic response to calcium in postmenopausal Chinese women.
AB  - AIM: To investigate the correlation between calcium treatment in postmenopausal
      women and estrogen receptor-alpha (ER-alpha) Xba I and Pvu II genotype and
      vitamin D receptor (VDR) Apa I genotype. METHODS: One hundred fifteen
      postmenopausal Chinese women of Han population were enrolled and treated with
      calcichew-D3 (1000 mg calcium and 400 U vitamin D3) daily for 1 year. At entry
      and after 1 year treatment, the bone mineral density (BMD), serum and urinary
      bone turnover biochemical markers were evaluated. ER-alpha and VDR genotype were
      analyzed using PCR-restriction fragment length polymorphism. RESULTS: After 1
      year of calcium supplementation, a significant increase of BMD and a marked
      reduction in serum ALP and PTH levels, and a significant increase of serum 25
      (OH) vitamin D level were observed (P<0.01 or P<0.05). At entry and after 1 year
      of treatment, no significant association was found between Xba I, Pvu II, and Apa
      I genotypes and BMD in L1-4, Neck, and Troch, and all bone turnover marker
      levels. However, the percentage of change (median, QR) in Neck BMD was
      significantly different in homozygous XX [-4.14 (from -6.54 to -1.34)] in
      comparison with Xx [1.72 (from -1.12 to 3.20)] (P<0.001) or xx [1.22 (from -1.74
      to 3.06)] Xba I ER-alpha genotype (P=0.001). CONCLUSION: Women with ER-alpha Xba
      I genotype XX may have a higher risk of relatively fast bone mass loss in femoral
      neck after menopause and that they may have a poor responsiveness to calcium
      supplementation. The changes in BMD are not associated with ER-alpha Pvu II
      genotype and VDR Apa I genotype after 1 year of calcium supplementation.

PMID- 15569418
TI  - Peplomycin induces G1-phase specific apoptosis in liver carcinoma cell line Bel
      7402 involving G2-phase arrest.
AB  - AIM: To investigate the mechanism of peplomycin (PEP)-induced apoptosis in liver
      carcinoma cell line (Bel-7402). METHODS: Growth inhibition by PEP was analyzed
      using 3- 4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay.
      Apoptotic cells were detected using Hoechest 33258 staining, and confirmed by
      flow cytometric analysis and DNA fragmentation analysis. The expression of cyclin
      A and B1 were determined by flow cytometry and Western blot. Annexin V assay was
      measured by flow cytometric analysis. RESULTS: PEP induced apoptosis and then
      inhibited cell proliferation in liver carcinoma cell line Bel-7402. Cells treated
      with PEP 50 mumol/L for 15 h were arrested in G2-phase with dramatical expression
      of cyclin A and a little change in cyclin B1. Almost all the apoptosis occurred
      in cells undergoing the G1-phase after treatment for 24 h. CONCLUSION: Peplomycin
      induced G1-phase specific apoptosis in Bel-7402 involving G2-phase arrest.

PMID- 15569419
TI  - A mutation in signal peptide of rat resistin gene inhibits differentiation of 3T3
      L1 preadipocytes.
AB  - AIM: To detect the resistin expression of white adipose tissue in diet-induced
      obese (DIO) versus diet-resistant (DR) rats, and to investigate the relationship
      of mutated resistin and 3T3-L1 preadipocytes differentiation. METHODS: RT-PCR and
      Western Blot were used to detect gene /protein expression. 3T3-L1 cells were
      cultured, transfected, and induced to differentiation using 0.5 mmol/L 3-isobutyl
      1-methylxanthine (MIX), 1 mg/L insulin, and 1 micromol/L dexamethasone. Oil red O
      staining was applied to detect the degree of preadipocytes differentiation.
      RESULTS: Expression of resistin mRNA was upregulated in DIO rats and
      downregulated in DR rats. However, the expression levels varied greatly within
      the groups. Sequencing of the resistin genes from DIO and DR rats revealed a
      Leu9Val (C25G) missense mutation within the signal peptide in one DR rat. The
      mutant resistin inhibited preadipocyte differentiation. Local experiments and
      Western blotting with tagged resistin fusion proteins identified both mutant and
      wild type proteins in the cytoplasm and secreted into the culture medium.
      Computer predictions using the Proscan and Subloc programs revealed four putative
      phosphorylation sites and a possible leucine zipper motif within the rat resistin
      protein. CONCLUSION: Resistin-increased differentiation may be inhibited by the
      mutation-containing precursor protein, or by the mutant non-secretory resistin
      isoform.

PMID- 15569420
TI  - Rational redesign of inhibitors of furin/kexin processing proteases by
      electrostatic mutations.
AB  - AIM: To model the three-dimensional structure and investigate the interaction
      mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c
      mutants). METHODS: The three-dimensional complex structures of furin/kexin with
      its inhibitors, eglin c mutants, were generated by modeller program using the
      newly published X-ray crystallographical structures of mouse furin and yeast
      kexin as templates. The electrostatic interaction energy of each complex was
      calculated and the results were compared with the experimentally determined
      inhibition constants to find the correlation between them. RESULTS: High quality
      models of furin/kexin-eglin c mutants were obtained and used for calculation of
      the electrostatic interaction energies between the proteases and their
      inhibitors. The calculated electrostatic energies of interaction showed a linear
      correlation to the experimental inhibition constants. CONCLUSION: The modeled
      structures give good explanations of the specificity of eglin c mutants to
      furin/kexin. The electrostatic interactions play important roles in inhibitory
      activity of eglin c mutants to furin/kexin. The results presented here provided
      quantitative structural and functional information concerning the role of the
      charge-charge interactions in the binding of furin/kexin and their inhibitors.

PMID- 15569421
TI  - [Attention to the prevention and treatment of childhood tuberculosis].

PMID- 15569422
TI  - [Childhood tuberculosis: epidemiology, prevention and treatment].

PMID- 15569423
TI  - [The epidemic of childhood tuberculosis in China].
AB  - OBJECTIVE: To analyze the epidemic situation of children Tuberculosis (TB) in
      China. METHODS: To sum up the data of four times national TB epidemic survey from
      1979 to 2000, and analyze the epidemic situation of children whose age were
      between 0 and 14. RESULTS: The TB prevalence rates in children were 8.8%, 9.6%,
      7.5% and 9.0% in 1979, 1984/85, 1990, 2000. The active pulmonary TB (PTB)
      prevalence rates in children were 241.7/100 000 172.1/100 000, 91.8/100 000 in
      1979, 1990 and 2000, the bacteriological positive PTB prevalence rates were
      12.7/100 000, 12.3/100 000 in 1990 and 2000, the smear positive PTB prevalence
      rates were 7.5/100 000, 7.5/100 000 and 6.7/100 000 in 1979, 1990 and 2000; It
      was estimated there were 26.08 million children who were infected by
      microbacterial TB, 266 thousands children active PTB cases, 36 thousands children
      bacteriological positive PTB cases and 19 thousands children smear positive PTB
      cases in 2000 according to the data of the national population survey. the rates
      were 4.5%, 5.9%, 1.8%, 1.3% when comparing them to the all patients. the ratio of
      children TB prevalence rates between city and country were 1.8, 1.8, 1.7 and 1.2
      in the four survey. CONCLUSIONS: The TB prevalence rates in children had not
      obvious decrease from 1979 to 2000 were not allowed to optimize to the epidemic
      of children TB. The bacteriological negative PTB had a bigger. The difference of
      children TB prevelance between city and country reduced gradually. The quantity
      of sample and other factors influenced the forecast value of PPD to disease, so
      it would be a trend of using the routine surveillance to replace the national
      epidemic survey. BCG still would be the an important content in our national TB
      control before the emergence of the new and more efficient vaccine.

PMID- 15569424
TI  - [Primary study on collagen X gene expression in the apical disc of idiopathic
      scoliosis].
AB  - OBJECTIVE: To study the distribution of collagen X in the intervertebral disc and
      determine its role in the pathogeny of idiopathic scoliosis (IS). METHODS: The
      data included apical disc and intermediate disc from 14 cases of AIS, 26 discs
      from 13 cases of scoliosis of confirmed pathogeny which included 10 cases of
      congenital scoliosis and neurofibromatosis scoliosis (CS group). Six discs were
      obtained from 3 cases of sudden death of normal young man served as controls. The
      distribution of collagen X in the apical disc of IS was examined by
      immunohistochemistry and in situ hybridization (ISH) with RNA probe. The figure
      of collagen X hybridization in the endplate cartilage was input to the figure
      analysis system. The mRNA content of collagen X was compared between every 2
      groups by SPSS software. RESULTS: Collagen X was mainly distributed around the
      hypertrophic chondrocyte in the endplate cartilage. Its mRNA was expressed in the
      hypertrophic chondrocyte. Positive signal was found in the nuclei of several
      scoliosis patients, which was not related to the pathogeny. The collagen X mRNA
      contents of the apical disc and intermediated disc of the IS group and of the CS
      group were significantly higher than those of the normal group (P < 0.05). There
      was no difference between the IS and CS groups. CONCLUSIONS: Collagen X is mainly
      distributed around the hypertrophic chondrocyte in the endplate cartilage. Its
      can also be secreted by the chondrocyte-like cells in the nucleus under special
      condition. Higher expression of collagn X gene in scoliosis patients may be the
      effects of long term abnormal stress which causes calcification of endplate
      cartilage. Collagen X expressed in the nucleus may be the result of secretion of
      chondrocyte-like cells in the disc under abnormal mechanical condition.

PMID- 15569425
TI  - [Association between genetic polymorphisms of CYP2C19 and CYP2C9 and phenytoin
      serum concentration].
AB  - OBJECTIVE: To investigate the relationship between the genetic polymorphism of
      cytochrome CYP2C19 and CYP2C9 and the serum concentration of phenytoin (PHT) in
      patients with epilepsy. METHODS: The peripheral blood samples of 200 patients
      with epilepsy aged 2 - 68, were collected to undergo PCR. Denaturing high
      performance liquid chromatography (DHPLC) was used to detect the PCR products so
      as to examined the 2 common CYP2C19 allele variants and one CYP2C9 allele. The
      patients were treated with PHT of the dosage of 1.00 - 18.02 mg/kg alone. After 5
      half-life periods venous blood was collected before the administration.
      Fluorescence polarization immunoassay was used to measure the PHT serum
      concentration standardized by dosage and body weight. RESULTS: The allele
      frequencies of CYP2C19 * 2, CYP2C19 * 3, and CYP2C9 * 3 were 31%, 8%, and 6%
      respectively. Thirty-two patients with CYP2C19 and/or CYP2C9 allele variants were
      classified into 3 groups: extensive metabolizer (EM, n = 11) homozygous for
      CYP2C19 * 1/* 1 combined with CYP2C9 * 1/* 1 alleles, intermediate metabolizer
      (IM, n = 14) heterozygous for CYP2C19 * 1/* 2 or CYP2C19 * 1/* 3 alleles, and
      poor metabolizer (PM, n = 7) with the genotype of CYP2C19 * 2/* 2 or CP2C19 * 2/*
      3, or CYP2C19 * 1/* 2 combined with CYP2C9 * 1/* 3. The genotype distribution
      rates of EM, IM, and PM were 34%, 44%, and 22% respectively. The PHT serum
      concentration of the PM group was (4.0 +/- 0.9) Css, significantly higher than
      that of the IM group [(3.0 +/- 0.9) Css, P < 0.05] and that of the EM group [(2.6
      +/- 0.8) Css, P < 0.01] without a significant difference between the IM group and
      EM group. CONCLUSION: Phenytoin is metabolized via CYP2C19 and CYP2C9. The PHT
      serum concentration of the PM is significantly higher. Genotyping helps predict
      the clinical response to PHT administration.

PMID- 15569426
TI  - [Dynamic changes of immunoglobulin G in convalescents who have suffered from
      severe acute respiratory syndrome patients].
AB  - OBJECTIVE: To investigate the dynamic changes of the antibody specific to severe
      acute respiratory syndrome (SARS) coronavirus in convalescents who have suffered
      from SARS. METHODS: Samples of peripheral blood were collected twice during the
      first 2 weeks after discharge and then once every 2 - 4 weeks from 310
      convalescents of SARS, 131 males and 179 females, aged 18 - 74, discharged from
      hospitals in Beijing April 3 to June 20 2003 with the average discharge date of
      June 10, to detect the level of immunoglobulin G (IgG) by ELISA. A curve of level
      of IgG was drawn to describe the change by the specific month in the year.
      RESULTS: Most of the 310 convalescents underwent successive or non-successive
      testing for 2 - 4 months and 15 were tested for 5 months, 15 for 6 months, and 2
      for 7 months. IgG was detected in each sample with the mean of A value of 0.97 +/
      0.37 (0.197 - 1.849). The mean IgG level peaked in July (1.203), about 35 days
      after discharge, and then gradually declined to 0.857 in December, a decline by
      27.3%. CONCLUSION: All SARS patients generate specific antibody against the
      coronavirus. However, the antibody level gradually decline with the lapse of time
      during the convalescence. Long-term surveillance of the change of antibody is
      necessary.

PMID- 15569427
TI  - [Extended transsphenoidal approach to giant tumors in sellar and clival area].
AB  - OBJECTIVE: To explore the effects of extended transsphenoidal approach, a new
      approach for removing giant tumors in sellar and clival area. METHODS: Twenty
      eight patients, 19 males and 9 females, aged 17 - 67 with a mean age of 47.8,
      with a mean history of 6.2 years, 13 with invasive giant pituitary adenoma, 10
      with chordoma, 2 with giant cell tumor of bone, 2 with pituitary metastatic
      tumor, and 1 with pituitary endocrinal carcinoma underwent operation by extended
      transsphenoidal approach. The tumors were 3.0 - 5.5 cm in size. In 2 cases the
      tumor extended to the base of the frontal lobe, 7 tumors involved the cavernous
      sinus, and 19 extended to clivus. RESULTS: The tumor was totally removed in 19
      patients, removed subtotally in 6 patients, and removed partially in 3 patients.
      Postoperative follow-up was performed for 6 months to 4 years. No recurrence
      occurred except for enlargement of 2 pituitary metastatic tumors and 1 chordoma.
      CONCLUSION: Extended transsphenoidal approach satisfactorily reaches and helps
      remove the giant tumors in sellar and clival area without severe complication.

PMID- 15569428
TI  - [Laparoscopic liver resection for benign liver tumors].
AB  - OBJECTIVE: To assess the feasibility, safety, and outcome of laparoscopic liver
      resection for benign liver tumors. METHODS: Fourteen patients with benign liver
      tumors, including 11 cases of hepatic hemangioma, 1 case of hepatic focal nodular
      hyperplasia, 1 case of hepatic granulomatous inflammation, and 1 case of liver
      cyst with hyaline degeneration and calcification underwent laparoscopic liver
      resection by PMOD. RESULTS: Hepatectomy was performed successfully under
      laparoscope in these 14 patients. There was no conversion to open approach, no
      postoperative mortality and no postoperative complication. The mean postoperative
      hospital stay was 6.4 days without recurrence. CONCLUSION: Laparoscopic liver
      resection of benign liver tumors by PMOD is feasible and safe for patients with
      symptomatic and undetermined hepatic tumor, and is applicable in hepatic
      hemangioma complicated with cholecystitis.

PMID- 15569429
TI  - [Generation of specific cytotoxicity T lymphocytes induced by tumor-derived heat
      shock protein 90-peptide complexes in vitro].
AB  - OBJECTIVE: To investigate the specific induction of cytotoxic lymphocyte (CTL) by
      tumor-derived heat shock protein 90-peptide complexes (HSP90-PC). METHODS: Heat
      shock protein 90-peptide complex (HSP90-PC) was isolated and purified by liquid
      chromatography after precipitation by 50% - 70% (NH4) 2SO4 saturation from 10
      specimens of renal carcinoma resected from 10 patients aged 40 - 60 during
      operation. The component containing HSP90-PC was filtered and sterilized. The
      molecular weight and the identity of the purified HSP90-PC were confirmed by SDS
      PAGE and Western blotting. 10 - 15 ml peripheral blood was extracted from these
      patients. T cells were amplified. Flow cytometry was used to detect the phenotype
      of dendritic cells (DCs). The DCs in the experimental group were cultured for 5
      days and then HSP90-PC and tumor necrosis factor (TNF)-alpha was added into the
      culture. The HSP90-PC pulsed DCs were collected and co-cultured with auto-T cells
      for 72 hours. Flow cytometry was used to detect the content of CD8(+) T cells.
      The DC of the control group were mixed directly with auto-T cells and the content
      of CD8(+) T cells was examined by flow cytometry. RESULTS: The proliferation of T
      cells co-cultured with the HSP90-PC pulsed DCs was significantly remarkable and
      the content of CD8(+) CTLs was significantly more in comparison with the control
      DC (P < 0.01). CONCLUSION: HSP90-PC prepared from tumor tissues has strong
      immunogenicity and the DC sensitized thereby effectively induces the
      proliferation of CTL. Application of HSP90-PC provides a new approach in tumor
      immunotherapy.

PMID- 15569430
TI  - [Frequent loss of heterozygosity at MEN-1 gene and chromosome 22q in insulinomas
      and its significance].
AB  - OBJECTIVE: To detecte whether loss of heterozygosity (LOH) at the MEN-1 locus as
      well as 22q occurs in sporadic insulinoma and if LOH can be used as a genetic
      marker to differentiate malignant and benign insulinomas. METHODS: MEN-1 gene and
      22q allelotyping were performed by PCR with microsatallite markers in DNA from
      microdissected normal and tumor tissues from archived or frozen insulinomas (8
      malignant and 32 benign, from 38 patients). The significance was calculated using
      t test and Cochran-Mantel-Haenszel Statistics, P < 0.05 was considered
      significant. RESULTS: Sixteen of the 40 insulinomas (40.0%) had MEN-1 LOH and 22q
      LOH was shown in 30 of the 40 tumors (75.0%). Eleven of the 30 tumors (37.0%)
      with 22q LOH had 22q12 LOH over a 3 cm region, whereas LOH in 14 tumors (47.0%)
      occurred at 22q13.3. Eight tumors with D22S 280 locus (22q12) LOH were shown
      without MEN-1 LOH while 14 of the 30 tumors without D22S280 LOH had MEN-1 LOH (0%
      vs 47%, P = 0.016). Six of the 14 tumors (43.0%) with 22q13.3 LOH were malignant,
      whereas 2 of 26 tumors without 22q13.3 LOH (8.0%) are malignant (P = 0.0088).
      CONCLUSION: MEN-1 gene LOH may contribute to a proportion of insulinomas, and 22q
      LOH occurs frequently in insulinomas. D22S 280 (22q12) LOH may independently
      contribute to the tumorogenesis of sporadic insulinoams, whereas detecting
      22q13.3 LOH in insulinomas can be a potential genetic marker to distinguish
      malignancy from benign tumors.

PMID- 15569431
TI  - [Study on the association of reaction of astrocytes with cyclin D1 protein in
      peripheral tissue of human brain hemorrhagic area].

PMID- 15569432
TI  - [Effects of clonidine combined with various local anesthetics in brachial plexus
      block].

PMID- 15569433
TI  - [Study on the remodeling of myocardial gap junctional protein connexin-40 of
      chronic atrial fibrillation in rheumatic heart valve disease].

PMID- 15569434
TI  - [Experimental study of in vitro chondrogenesis by co-culture of bone marrow
      stromal cells and chondrocytes].
AB  - OBJECTIVE: Chondrogenic microenvironments play a very important role in
      chondrogenesis of bone marrow stromal cells (BMSC). This study explored the
      feasibility of in vitro chondrogenesis by co-culture of BMSC and chondrocytes so
      as to confirm the hypothesis that chondrocytes can provide chondrogenic
      microenvironment to induce chondrogenic differentiation of BMSC and thus promote
      in vitro chondrogenesis of BMSC. METHODS: Porcine BMSC and auricular chondrocytes
      were in vitro expanded respectively and then were mixed at a ratio of 8:2
      (BMSC:chondrocyte). 200 microl mixed cells(5.0 x 10(7)/ml) were seeded onto a
      polyglycolic acid/polylactic acid (PGA/PLA) scaffold, 9 mm in diameter and 3 mm
      in thickness, as co-culture group. Chondrocytes and BMSC with the same cell
      number were seeded respectively onto the scaffolds as positive control
      (chondrocyte group) and negative control (BMSC group). 200 microl chondrocytes
      (1.0 x 10(7)/ml, equal to the chondrocyte number of co-culture group) alone were
      seeded as low concentration chondrocyte group. There were 6 specimens in each
      group. All specimens were harvested after in vitro culture for 8 weeks in DMEM
      plus 10% FBS. Gross observation, average wet weight measurement,
      glycosaminoglycan (GAG) quantification, histology and immunohistochemistry were
      used to evaluate the results. RESULTS: Cells in all groups had fine adhesion to
      the scaffolds and could secrete extracellular matrix. In both co-culture group
      and positive control group, the cell-scaffold constructs could maintain the
      original size and shape during in vitro culture and formed homogenous mature
      cartilage after 8 weeks of in vitro culture. Furthermore, the neo-cartilages in
      both groups were similar to each other in gross appearance and histological
      features, and abundant type II collagen was also detected by immunohistochemistry
      in both groups. The average wet weight and GAG content of co-culture group were
      both more than 80% of those of positive control group. In negative control group,
      however, the constructs shrunk gradually during in vitro culture and cartilage
      like tissue could only be observed at the edge area of the construct. In low
      concentration chondrocyte group, the constructs also shrunk gradually during in
      vitro culture and the average wet weight was below 40% of that of the positive
      control group although histology showed a small amount cartilage formation.
      CONCLUSION: Chondrocytes can provide a chondrogenic microenvironment to induce a
      chondrogenic differentiation of BMSC and thus promote the in vitro chondrogenesis
      of BMSC.

PMID- 15569435
TI  - [Telomerase antisense inhibition and chemotherapeutic combination treatments for
      the proliferation of endometrial cancer in vitro and in vivo].
AB  - OBJECTIVE: To investigate the antitumor effects of telomerase antisense
      oligodeoxynucleotide (AODN). METHODS: Human endometrial cancer cells of HEC-1A
      line were cultured at the concentrations of 0.8 and 1.6 micromol/L respectively
      and transfected with human telomerase AODN, as telomerase inhibitors, twice. 24,
      48, 72, 96, and 128 hours after the first transfection MTT method was used to
      detect the absorbance at the wave length of 490 nm so as to determine the cell
      survival rate. HEC-1A cells were collected after transfection of 0.05, 0.1, 0.2,
      0.4, and 0.8 micromol/L of AODN and the total DNA was extracted. Reverse
      transcription-polymerase chain reaction (RT-PCR) was used to examine the
      expression of hTERT mRNA. Telomeric repeat amplification protocol (TRAP)-ELISA
      was used to detect the activity of telomerase. HEC-1A cells were injected
      subcutaneously into the axillary fossae of Balb/c nude mice, Four days after when
      tumors were touchable the nude mice were divided into 5 groups to undergo
      intratumoral injection of high-dosage ADON (25 mg/kg, 1/d), low-dosage ADON (12.5
      mg/kg, 1/d), cis-dichlorodiamine plastinum (DDP, cisplatin, 12.5 mg/kg, 1/d),
      AODN + DDP (AODN 12.5 mg/kg and DDP 5 microg/kg, 1/d alternatively), and normal
      saline respectively. The tumor size, tumor weight, and tumor relative volume were
      measured and calculated. Twenty-one days after the mice were killed and their
      organs were examined. RESULTS: AODN effectively and dose-dependently inhibited
      the growth of HEC-1A cells. There was a plateau of inhibition. The inhibition
      rate rose further 4 days after transfection. Five days after transfection the
      proliferation inhibition rate of AODN of the concentrations of 0.4, 0.8, and 1.6
      microm were 46.35%, 65.22%, and 79.45% respectively. The relative inhibition rate
      of hTERT mRNA expression increased dose-independently along with the increase of
      concentration of transfected AODN. The tumor inhibition rate of nude mice were
      34.20%, 89.21%, 79.82%, and 72.41% in the low-dosage AODN group, high-dosage AODN
      group, DDP group, and AODN + DDP group respectively. However, AODN began to show
      significant inhibitory effect 8 days after administration. The tumor inhibition
      rate of the AODN+DDP group was 72.4%, similar to those of the high dosage AODN
      and DDP groups (both P < 0.05). The telomerase activity in tumor of the AODN (25
      mg/kg) group was 509 +/- 377, decreased by 87.23% in comparison with that of the
      control group (64 +/- 23, P < 0.05). CONCLUSION: Antisesne oligonucleotide of
      hTERT effectively inhibits the abnormal activation of telomerase, thus the growth
      of endometrial cancer cells. Telomerase inhibitor may be a new strategy for
      chemotherapy or chemoprevention in endometrial cancer.

PMID- 15569436
TI  - [Effects of continuous early enteral nutrition on the gut barrier function in
      dogs with acute necrotizing pancreatitis].
AB  - OBJECTIVE: To evaluate the effects of continuous early enteral nutrition on the
      gut barrier function in acute necrotizing pancreatitis (ANP). METHODS: Thirty
      mongrel dogs underwent laparotomy and 5% mixed solution of sodium taurocholate
      with trypsin was infused into the pancreatic ducts so as to induce model of ANP.
      Permanent duodenal and jejunal fistulas were retained. Then the 30 dogs were
      randomly divided into 6 groups of 5 dogs: total parenteral nutrition (TPN) group,
      normal saline (NS) group, duodenal nutrison multifibre (DN) group, duodenal PEPTI
      2000Varient (DP) group, jejunal nutrison multifibre (JN) group, and jejunal PEPTI
      2000Varient (JP) group, the last 4 groups being called enteral nutrition (EN)
      group together. Infusion of nutritional solutions was performed via the duodenal
      or jejunal fistulas, beginning 24 hours after the operation and lasting for 5
      days. The levels of endotoxin and D-(-)-lactate in the peripheral plasma were
      measured every day. On the days 2 and 5 after the operation test solution to
      measure the enteral permeability, containing lactulose and mannitol, was infused
      via the fistulas and then urine within 6 hours thereafter was collected to detect
      the concentrations of lactulose and mannitol and calculate the lactulose/mannitol
      ratio. Seven days after the operation the dogs were killed to take the pancreas
      and intestines to be examined by microscopy. Feces was collected. ERIC-PCR
      fingerprint method was used to examine the structure and distribution of ERIC
      series of the microbial communities in the gut. RESULTS: The plasma D-(-)-lactate
      of the NS group gradually increased and peaked on the 5th day after the
      operation, and that of the TPN group gradually increased too, however, lower than
      that of the NS group at any time points and was significantly lower on the 5th
      day (P < 0.05). The plasma D-(-)-lactate of the EN groups increased first and
      then decreased and was lower than those of the TPN and NS groups with significant
      differences on the 4th and 5th days (all P < 0.05). Five days after the operation
      the lactulose/mannitol ratio decreased in every groups and with significant
      differences between the EN groups and TPN and NS groups and between the TPN and
      NS groups (all P < 0.05). The plasma endotoxin level increased in every groups,
      however, the endotoxin levels of the EN groups at any time points were all lower
      than those of the TPN group and much more lower than those in the NS group with
      significant differences between the EN groups and TPN group and NS group on
      specific days after operation (all P < 0.05). The pathological changes of the
      intestinal mucosa were more severe in the NS group than in the TPN group, and
      much more severe than in the EN groups. The makeup and distribution of intestinal
      microbial in the EN groups were similar to those of the normal dogs. However, the
      makeup and distribution of intestinal microbial in the TPN groups were quite
      different from those of the normal dogs. CONCLUSION: EN helps maintain gut
      mucosal barrier, decreases endotoxin translocation, and decreases the extent of
      mucosal atrophy in ANP.

PMID- 15569437
TI  - [The inhibitory effects of angiostatin on retinal neovascularization induced by
      oxygen].
AB  - OBJECTIVE: To observe the inhibitory effects of angiostatin on microvascular
      endothelial cells of mouse retina and test the efficacy of native angiostatin in
      suppressing experimental retinal neovascularization induced by oxygen. METHODS:
      Angiostatin was purified with L-lysine Sepharose 4B from human plasma. The
      primary microvascular endothelial cells from rat retina were cultured.
      Microvascular endothelial cells growth inhibition assay was carried out with MTT
      method. Mouse models of hyperoxia-induced ischemic retinopathy were established.
      Angiostatin or normal saline (NS) were injected into the vitreous in 5 groups:
      normal, control and various doses. The nuclei of new vessel buds extending from
      the retina into the vitreous in different groups were counted and compared under
      the light microscope. RESULTS: Angiostatin could inhibit the growth of
      microvascular endothelial cells from rat retina in vitro. There were plenty of
      new vessel buds in the eyes of all mice in hyperoxic condition. The number of the
      nuclei of new vesselbuds in the murine eyes with injection of angiostatin. They
      were reduced by 42% (P < 0.01), 57% (P < 0.01) and 82% (P < 0.01) respectively.
      CONCLUSION: Angiostatin can powerfully inhibit growth of microvascular
      endothelial cells. The proliferation of retinal vessel may be suppressed by using
      angiostatin.

PMID- 15569438
TI  - [Effect of hemin on chronic kidney failure in rats].

PMID- 15569439
TI  - [Latent tuberculosis infection in children and decision analysis of tuberculosis
      pure protein derivative skin testing].

PMID- 15569440
TI  - [Short-course chemotherapy for tuberculosis in childhood].

PMID- 15569441
TI  - [Early diagnosis of tuberculosis meningitis in children and its differential
      diagnosis].

PMID- 15569442
TI  - [Anti-tuberculosis drug resistance in children and its countermeasure].

PMID- 15569443
TI  - [Intrathecal implantable infusion pumps in the treatment of refractory pain-
      report of 3 cases].

PMID- 15569444
TI  - [Repeated cough, hemoptysis, diffuse shadow in bilateral lungs--a case report].

PMID- 15569445
TI  - [Ureteral fibril-epithelial polyps--a case report].

PMID- 15569447
TI  - [Therapy of deep vein thrombosis of the lower extremity].

PMID- 15569448
TI  - [The treatment level of heart transplantation in China should be further raised].

PMID- 15569449
TI  - [Several issues in study of severe acute respiratory syndrome].

PMID- 15569450
TI  - [Orthotopic heart transplantation: clinical experience on 56 patients].
AB  - OBJECTIVE: To summarize the clinical experience on 56 patients undergoing
      orthotopic heart transplantation. METHODS: Between May 2000 and December 2003 56
      patients, 47 with cardiomyopathy, 2 with end-stage valvular heart disease, 2 with
      end-stage ischemic heart disease, 2 with primary malignant cardiac tumor, 1 with
      complicated congenital heart disease, 1 with muscular dystrophy cardiomyopathy,
      and 1 with refractory malignant ventricular arrhythmias, underwent orthotopic
      heart transplantation in the Transplantation Center of Fudan University. The
      operative procedures included 19 conventional Stanford orthotopic cardiac
      transplantation in 19 cases and bicaval anastomotic cardiac transplantation in 37
      cases. Postoperatively, the patients were prescribed with cyclosporine A +
      corticosteroids + MMF or FK506 + corticosteroids + MMF as anti-rejection therapy.
      RESULTS: One patient undergoing his fifth operation died of bleeding 3 days after
      operation. All survivors were followed-up for 12.4 months on average. Five
      patients died within 1 year postoperatively with a one-year survival rate of 91%.
      One patient died of allograft vasculopathy 38 months after operation. Other
      patients enjoyed heart function recovering to class I-II (NYHA). CONCLUSION: With
      proper recipient selection, excellent donor heart conservation, bicaval
      anastomotic technique, and efficient postoperative surveillance and treatment,
      heart transplantion may produce satisfying mid-term results.

PMID- 15569451
TI  - [Transcatheter closure of perimembranous ventricular septal defects using the new
      Amplatzer membranous VSD occluder: a short-term evaluation].
AB  - OBJECTIVE: To evaluate the efficacy of transcatheter closure of perimembranous
      ventricular septal Defects (VSD) using the new Amplatzer membranous VSD occluder
      in a short-term follow-up. METHODS: From November 2002 to November 2003, forty
      eight patients (25 male, 23 female) with perimembranous VSD underwent an attempt
      of catheter closure using a new device specially designed for the membranous
      septum. The mean age of patients was 17 years +/- 12 years (ranged from 3 to 48
      years); the mean diameter of VSD measured by transthoracic echocardiography (TTE)
      was 5.1 mm +/- 1.2 mm (ranged from 3 to 12 mm). Occluder was released through
      right heart system. All patients would undergo follow-up 1 months, 3 months, 6
      months and 12 months after procedures with examination of transthoracic
      echocardiography, radiography, and electrocardiography. RESULTS: The devices were
      deployed successfully in 45 patients. there was complete closure in 36 patients
      immediately, and tiny (< 3 mm) residual shunt in 5 patients. at the follow-up of
      3 months, only two of all patients had a tiny residual shunt. Complete left
      bundle branch block (LBBB) was found in one patients when he was examined in
      electrocardiograph 2 weeks later, there were no other severe complications. On a
      follow-up of 1 to 12 months (mean 3.8 months), all patients were demonstrated a
      great decrease in their left ventricle end-diastolic dimension (LVEDD) (P < 0.05)
      and no other late complications. CONCLUSION: Transcatheter closure of membranous
      VSD using this new occluder is safe and effective, the results of short-term
      follow-up was satisfied. Further clinical trials are underway to assess the long
      term results.

PMID- 15569452
TI  - [Dynamic change of apoptosis of alveolar cells in ischemia-reperfusion induced
      pulmonary injury: an experimental study with rats].
AB  - OBJECTIVE: To observe the dynamic changes of alveolar apoptosis in ischemia
      reperfusion (IR) induced pulmonary injury, and to evaluate the roles of these two
      cell death styles, apoptosis and necrosis, in the progress of lung function
      deterioration in pulmonary IR injury. METHODS: Fifty-four Sprague-Dawley rats
      were made ischemia/reperfusion models by ischemia and reperfusion in situ in
      single lung. Thirty-six of the 54 rats in the experimental group were re-divided
      into 6 equal subgroups to undergo detection of partial pressure of oxygen (PaO2)
      of blood in left atrium, detection of lung tissue wet weight/dry weight ratio,
      histology of lung by light microscope, examination of ultrastructural changes of
      cells by transmission electron microscopy, and quantitative detection of
      apoptotic cells in the right middle lobe by terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) 0 h, 0.5 h, 1 h, 2 h, 6 h, and 12 h
      respectively after the reperfusion (subgroups R0, R(0.5), R1, R2, R6, and R12).
      Another 18 rats in the experimental group were re-divided into 3 subgroups of 6
      rats to undergo insertion of venous catheter into the main pulmonary artery via
      right ventricle to perfuse trypan blue so as to evaluate the cell death degree.
      The death index was observed under light microscope and the necrosis index was
      indirectly calculated by the equation: death index = apoptotic index + necrosis
      index. Thirty-six rats underwent sham operation. Twelve rats were used as
      preoperative blank controls. RESULTS: Proliferation of alveolar type II, but not
      alveolar type I cell, accompanied by ultrastructural morphological changes were
      seen 1 h, 2 h, and 6 h after reperfusion, the most prominently 2 h after
      reperfusion. Apoptotic index was elevated since 1 h after reperfusion, and peaked
      2 h after reperfusion. Statistical analysis indicated that, compared with
      apoptotic index, the necrotic index was of more prominent correlation with blood
      oxygen partial pressure and wet/dry weight ratio. CONCLUSION: Alveolar apoptosis
      occurs in the early stage of reperfusion, and becomes the most prominent 2 h
      after reperfusion. Most apoptotic cells are alveolar type II cells. In the two
      styles of cell death in pulmonary IR injury, alveolar necrosis is more
      prominently correlated with progress of lung function deterioration.

PMID- 15569453
TI  - [Polymorphism of angiotensin converting enzyme gene and natural longevity in the
      Xinjiang Uygur people: an association study].
AB  - OBJECTIVE: To explore the distribution of I/D polymorphisms of angiotensin
      converting enzyme (ACE) gene and its relation to natural longevity in the
      Xinjiang Uygur people. METHODS: Polymerize chain reaction, single strand
      conformation polymorphism, and direct sequencing technique were used to test the
      I/D polymorphisms of ACE gene in 42 centenarians, 102 people aged 90-99, 70
      people aged 65-70, 53 cases of natural death aged 65-70 were used as controls.
      RESULTS: The frequencies of ACE genotypes DD, DI, and II were 28.6%, 30.9%, and
      40.5% respectively in the centenarian group, the frequency rates of D and I
      alleles were 0.44 and 0.56. The frequency rate of D/D genotype of the centenarian
      group was significantly higher than that of the group aged 65-70 (28.6% vs.
      12.9%, chi2 = 4.25, P < 0.05), however, not significantly different from that of
      the group aged 90 (P > 0.05). The frequency rate of D allele of the group of
      centenarian was significantly higher than that of the group aged 65-70 (44.0% vs.
      36.4%, chi2 = 4.47, P < 0.05). The frequency rates of genotype D/D and D alleles
      were significantly higher in the centenarian group than in the controls (both P <
      0.01). CONCLUSION: ACE gene polymorphism is closely correlated with life span of
      individuals. Longevity is the result of pleiotropic age-dependent influence of
      multiple factors.

PMID- 15569454
TI  - [Serum osteoprotegrin and serum bone gamma-carboxyglutamine acid-containing
      protein are correlated with bone mineral density in normal women].
AB  - OBJECTIVE: To study the relationships of serum osteoprotegrin (sOPG), serum bone
      gamma-carboxyglutamine acid-containing protein (sBGP), and urine
      deoxypyridinoline (uDPD)/creatinine (Cr) with age and bone mineral density (BMD)
      in women. METHODS: ELISA was used to examine the sOPG, sBGP, and uDPD/Cr of 672
      female volunteers aged 20-80. The BMD (QDR4500A) value of the anteroposterior
      lumbar spine and femoral neck were measured by DXA. RESULTS: (1) The levels of
      sOPG, sBGP, and uDPD/Cr in the age group of 30-39 were 2.8 pmol/L +/- 1.4 pmol/L,
      5 microg/L +/- 3 microg/L, and 4.9 nmol/mmol +/- 2.5 nmol/mmol respectively, all
      significantly lower than those in the age groups 40-49, 50-59, and 60-69 (all P <
      0.05). (2) In the age group 40-49, the values of sOPG, sBGP, and uDPD in
      menopausal subjects were significantly higher than those of the non-menopausal
      subjects (5.7 pmol/L +/- 3.1 pmol/L vs 3.4 pmol/L +/- 2.0 pmol/L, 11 microg/L +/-
      5 microg/L vs 6 microg/L +/- 3 microg/L, and 6.9 nmol/mmol +/- 3.3 nmol/mmol vs
      5.2 nmol/mmol +/- 3.9 nmol/mmol, all P < 0.001). (3) Age was positively
      correlated with sOPG, sBGP, uDPD/Cr, and BMD of anteroposterior lumbar spine and
      femoral neck (r = 0.130, 0.355, 0.106, -0.600, -0.545; P < 0.01). sOPG and sBGP
      were negatively correlated to anteroposterior lumbar spine BMD (r = -0.183, 
      0.108, P < 0.01; and r = -0.541, -0.441, P < 0.001). sOPG was positively
      correlated with sBGP and uDPD/Cr (r = 0.216 and 0.083; both P < 0.05).
      CONCLUSION: sOPG, sBGP, and uDPD/Cr can be used as sensitive markers to determine
      the bone turnover status, which is changeable with age, and menopausal status in
      women, and predict the bone lose prior to BMD determination by DXA.

PMID- 15569455
TI  - [Mutations in beta myosin heavy chain gene: two mutations in Chinese with
      familial hypertrophic cardiomyopathy and the correlation between the genotype and
      phenotype].
AB  - OBJECTIVE: To study the disease-causing gene mutation in Chinese with
      hypertrophic cardiomyopathy (HCM), and to analyze the correlation between the
      genotype and phenotype. METHODS: Samples of peripheral blood were collected from
      five Chinese patients with HCM in whose families at least 2 HCM patients existed.
      The exon in the functional regions of the beta myosin heavy chain gene (beta-MHC)
      were amplified with PCR and the products were sequenced. The relation between the
      genotype and phenotype was analyzed. RESULTS: Two mutations were first
      identified. Eighty controls were normal in the genetic test. CONCLUSION: beta-MHC
      may be the main disease-causing gene. Two mutations have different phenotypes. In
      one family, the identical mutation has different phenotypes and prognoses. The
      heterogeneity of phenotype suggests that multiple factors be involved in the
      pathogenesis.

PMID- 15569456
TI  - [Activation of receptor for advanced glycation end products: a mechanism for
      monocyte-mediated inflammation in chronic renal failure].
AB  - OBJECTIVE: To investigate the expression of receptor for advanced glycation end
      products (RAGE) in chronic renal failure (CRF) and its role in monocyte-mediated
      inflammation associated with chronic renal failure (CRF). METHODS: Peripheral
      monocytes (PMC) were isolated from 96 non-diabetic patients with varying severity
      of CRF. RAGE expression on monocytes was quantitated by flow cytometry. The
      binding capacity of monocytes with advanced glycation end products (AGE) was
      determined by 125I-AGEs-HSA binding assay. The plasma level of pentosidine, a
      marker of AGE, was determined by competitive ELISA. Commercially available kits
      were used for measuring the plasma levels of neopterin, TNF-alpha and C-reactive
      protein (CRP), a systemic acute phase reactant. RESULTS: Flow cytometry showed
      that the RAGE expression at the PMC surface of CRF patients was 8.02 +/- 0.43,
      significantly higher than that of the normal controls (P < 0.001). The number of
      functional sites to bind 125I-AGEs-HSA at the surface of PMC of CRF patients was
      increased in comparison with the normal control group. The biding capacity (Ka)
      at the surface of PMC of CRF patients was 2 times that of normal control group.
      Stimulated by AGEs-HAS, the TNF-alpha level in the supernatant of PMC increased
      dose-dependently in both the normal control and CRF patients, especially in the
      latter (P < 0.01). After pretreatment of anti-RAGE or non-immune rabbit IgG and
      then by AGEs-HAS the levels of TNF-alpha in the PMC supernatants of CRF patients
      and normal controls decreased form 90.52 pg/(10(5) cell) +/- 2.82 pg/(10(5) cell)
      to 17.86 pg/(10(5) cell) +/- 1.05 pg/(10(5) cell) and from 26.38 pg/(10(5) cell)
      +/- 1.54 pg/(10(5) cell) to 6.76 pg/(10(5) cell) +/- 0.20 pg/(10(5) cell). HAS
      not modified by AGEs and non-immune rabbit IgG showed no influence on the
      secretion of TNF-alpha. The plasma levels of TNF-alpha, neopterin, and CRP
      increased along with the worsening of renal function. The RAGE expression and
      pentosidine level at the surface of PMC in CPR patients without hemodialysis were
      positively correlated with plasma neopterin, TNF-alpha, and CRP levels, even
      after correction of creatine clearance rate (r = 0.53, P < 0.001; r = 0.58, P <
      0.001; r = 0.40, P = 0.001). The expression of RAGE in CRF patients with
      hemodialysis was positively correlated with the plasma TNF-alpha level (r = 0.33,
      P = 0.029, n = 36), however, not correlated with neopterin or CRP. CONCLUSION:
      Enhanced RAGE may trigger a positive feed back loop of AGEs-induced monocyte
      perturbation, and may contribute to the monocyte-mediated systemic inflammation
      in CRF.

PMID- 15569457
TI  - [Mutation of von Hippel-Lindau gene and expression of vascular endothelial growth
      factor in sporadic clear cell renal cell carcinoma and their relationships to
      angiogenesis].
AB  - OBJECTIVE: To evaluate the relationship between the mutation of the von Hippel
      Lindau (VHL) gene and expression of vascular endothelial growth factor (VEGF) in
      sporadic clear cell renal cell carcinoma (CCRCC) and angiogenesis. METHODS:
      Polymerase chain reaction (PCR) was used to detect the mutation of VHL gene in
      the specimens of cancerous tissue and normal tissues away from tumor from 77
      patients with CCRCC. Immunohistochemistry was used to examine the expression of
      VEGF. CD34 staining was used to measure the microvascular density (MVD). RESULTS:
      VHL gene mutations were detected in 40 cases (51.9%). The expression rate of VEGF
      was 79.2% (61 cases). The positive rate of VEGF in the cases with VHL mutation
      was 92.5%, significantly higher than that in the cases without VHL mutation
      (64.9%, P = 0.003). The levels of MVD was higher in the cases with VHL mutation
      and those with VEGF expression were 760.80/mm2 and 715.95/mm2 respectively, both
      significantly higher than those in the cases without VHL-mutation and those
      without VEGF expression (547.03/mm2 and 437.44/mm2 respectively, all P = 0.001).
      The cases with expression of VEGF were divided into two groups according the
      presence or absence of VHL gene mutations or not. The MVD of the cases with VEGF
      expression and VHL mutation was 760.80 mm2, significantly higher than that of the
      cases with VEGF expression and without VHL mutation (547.03 mm2, P = 0.011).
      CONCLUSION: The mutation rate of VHL gene is high among the Chinese with sporadic
      CCRCC. VHL gene mutation increases significantly the VEGF expression, thus, and
      perhaps via other mechanism too, promoting the angiogenesis in tumor. The high
      level of MVD of the cases with VHL gene mutation may be related to the high
      malignant potential of CCRCC.

PMID- 15569458
TI  - [Distribution of IgG subclass of anti-myeloperoxidase antibodies in sera from
      patients with propylthiouracil induced vasculitis].
AB  - OBJECTIVE: To investigate the distribution of IgG subclass of anti
      myeloperoxidase (MPO) antibodies, a kind of antineutrophil cytoplasmic
      autoantibody (ANCA), in sera from patients with propylthiouracil (PIU)-induced
      vasculitis. METHODS: Serum samples were collected from 12 patients with PIU
      induced MPO ANCA positive vasculitis, both sera of active and remission phases
      were collected from 10 of which, and only serum of active phase was collected
      from 2 of which. Anti-MPO IgG subclasses were detected by antigen-specific ELISA.
      The distribution of anti-MPO IgG subclasses in PIU-induced vasculitis was
      compared with that in primary vasculitis. RESULTS: Anti-MPO IgG3 subclass was not
      detected in the sera from both active and remission phases of PIU-induced
      vasculitis. In the active phase the following anti-MPO IgG subclasses were found:
      IgG1 (12/12, 100%), IgG2 (1/12, 66.7%), and IgG4 (7/12, 58.3%). In the remission
      phase, the following anti-MPO IgG subclasses were found: IgG1 (9/10, 90%), IgG2
      (4/10, 40%), and IgG4 (2/10, 20%). The titer of anti-MPO IgG4 subclass remained
      high in the remission phase in primary vasculitis; however, it decreased
      significantly after the cessation of PIU use in PIU-induced vasculitis.
      CONCLUSION: The distribution of anti-MPO IgG subclasses in the sera of the
      patients with PIU-induced vasculitis is different from that of the patients with
      primary vasculitis. The higher titer pf MPO-ANCA in the sera of the patients with
      PIU-induced vasculitis may be associated with the repeated PIU stimulation.

PMID- 15569459
TI  - [Anti-endothelial cell antibodies in systemic vasculitis: detection and
      correlation with disease activity].
AB  - OBJECTIVE: To investigate the prevalence of anti-endothelial cell antibodies
      (AECA) in systemic vasculitis and to assess the correlation between AECA and
      disease activity, and try to discuss the classification of AECA. METHODS: Cyto
      ELISA with EA.hy926 and HMEC-1, two immortalized cell lines, as substrates, was
      applied to detect AECA in 122 cases of systemic vasculitis, including 43 cases of
      Behcet disease, 19 cases of Takayasu arteritis, 19 cases of Wegener's
      granulomatosis, 11 cases of microscopic polyangiitis, 9 cases of polyarteritis
      nodosa, 3 cases of Churg-Strause syndrome, 2 cases of giant cell arteritis and
      other 16 cases of which could not be classified clearly. Patients with SLE, RA,
      and fever of unknown origin, and normal persons were used as control groups. Then
      the associations of AECA to laboratory findings and clinical disease activity
      (scored by BVAS) were analyzed. Furthermore, the AECA value from the two
      different substrate cells were analyzed for correlation and difference. RESULTS:
      With either EA.hy926 or HMEC-1 as substrates, the AECA prevalence rates of
      systemic vasculitis (respectively 33.61% and 37.70%) were significantly higher
      than those of the normal and RA groups (less than 10%), and the prevalence of
      AECA in SLE (61.75%) was higher than that of systemic vasculitis (37.70%) when
      using HMEC-1 as substrates. AECA was found to correlate very well with ESR in 122
      cases of systemic vasculitis and with BVAS in 40 cases of small systemic
      vasuculitides, including Wegener's disease, microscopic polyangiitis, Churg
      Strause syndrome and so on. The pair AECA values with EA.hy926 and HMEC-1 as
      substrate cells were found to be correlated significantly, and the matching rate
      was 92.62%. CONCLUSION: Prevalence of AECA in systemic vasculitis is high. AECA
      indicates the clinical disease activity. As to the assumption of classification
      of AECA into antibodies against microvascular and macrovascular endothelial
      cells, further study need to be done to prove or disprove it.

PMID- 15569460
TI  - [Expression of TRAIL(114-281) mediated by adeno-associated virus and its
      tumoricidal activity].
AB  - OBJECTIVE: To investigate the expression of the soluble tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) mediated by adeno-associated virus
      (AAV) and its tumoricidal activity in vitro and vivo. METHODS: The recombinant
      AAV expression vector encoding the extracellular domain (114-281aa peptide,
      TRAIL(114-281)) of TRAIL was constructed and transfected into human embryotic
      kidney cells HEK293 for virus package. The human tumor cell lines of T lymphocyte
      leukemia Jurkat, liver cancer HepG2 and SMMC-7721, and cervical cancer HeLa were
      transduced by using the recombinant virus particles respectively. The recombinant
      virus particles were also injected into C57BL/6 mice via the hepatic portal vein
      or hypodermic, intramuscular, celiac and oral pathways to study the expression of
      TRAIL(114-281). The recombinant virus titer was determined by real-time PCR. The
      expression of TRAIL(114-281) was evaluated by ELISA, Western blotting and
      immunohistochemistry assay respectively. The tumoricidal activity and apoptosis
      were evaluated by MTT assay. RESULTS: The recombinant AAV encoding for the
      soluble TRAIL (114 - 281aa) were constructed successfully. The titer of
      recombinant virus was 7.5 x 10(12) genome particles (Gps)/ml. Transduction of
      rAAV-TRAIL(114-281) led to high level expression of TRAIL(114-281) and the
      induction of apoptosis of Jurkat, Hela and SMMC-7721 cancer cells, but not HepG2
      cells, in vitro. The recombinant peptide TRAIL(114-281) in trimeric active form
      was highly and constantly expressed in the hepatocytes and secreted into the
      serum up to 6 months in the of C57BL/6 mice injected with the recombinant virus
      particles via the hepatic portal vein. The peptide TRAIL(114-281) in the livers,
      but not other tissues, were also detected in the mice administrated with rAAV
      TRAIL(114-281) particles via subcutaneous, intramuscular, intraceliac or oral
      pathway. CONCLUSION: The long term, stable and liver-tropism expression of
      peptide TRAIL(114-281) in mice mediated by rAAV-TRAIL(114-281) provides a
      prospective novel strategy for tumor gene therapy of numerous cancers, especially
      liver cancer.

PMID- 15569461
TI  - [Effect of down regulation of laminin receptor on urokinase-type plasminogen
      activator expression in human bile duct carcinoma cells].
AB  - OBJECTIVE: To investigate the effect of antisense oligonucleotide (AS-OD) of
      laminin receptor (LNR) on urokinase-type plasminogen activator (u-PA) expression
      in human bile duct carcinoma cells. METHODS: Bile duct carcinoma cells of QBC939
      line were cultured. Compounds of lipofectAMINE and AS-OD phosphorothioate of LNR
      of the concentrations of 3, 6, and 12 micromol/L respectively were prepared and
      then transfected into the QBC939 cells. Sense oligodeoxynucleotide (S-OD) of LNR
      and blank vector were used as controls. After culture of 48 hours, flow cytometry
      was used to detect the protein expression of LNR and the u-PA mRNA expression was
      detected by reverse-transcriptase polymerase chain reaction (RT-PCR). Cell
      invasion was examined by culture plate with Transwell microporous film before and
      after transfection. RESULTS: Flow cytometry showed down-regulation of LNR protein
      expression in the cells transfected with AS-OD dose-dependently. The LNR protein
      expression of the cells transfected with AS-OD of the concentration of 6
      micromol/L was down-regulated by over 25% in comparison with those of the blank
      vector group and S-OD group (both P < 0.05). RT-PCR showed that the u-PA mRNA
      expression of the AS-OD 6 micromol/L group was down-regulated by 30% in
      comparison with the 2 control groups. The number of migrating cells in the AS-OD
      group was 78 +/- 6, significantly lower than those in the S-OD group (105 +/-
      11), and blank vector group (101 +/- 7), both P < 0.05. CONCLUSION: The
      expression of laminin receptor in the bile duct carcinoma cells is related with
      the expression of u-PA gene expression. Inhibition of LNR expression decreases
      the u-PA gene expression, suggesting that LNR plays an important role in the
      invasion and metastasis of bile duct carcinoma.

PMID- 15569462
TI  - [Effect of free fatty acid-induced insulin resistance on plasma ghrelin level: an
      experimental study with rats].
AB  - OBJECTIVE: To investigate the effect of free fatty acid-induced insulin
      resistance on plasma ghrelin level. METHODS: A venous catheter was inserted
      through the right jugular vein into the right atrium, and an arterial catheter
      was inserted through the left carotid in 24 SD rats. After at least 5 days the
      rats underwent clamping of pancreas after fasting of 12-14 hours. Then the rats
      were divided into 2 equal groups: lipid-infused group (lipid/heparin were infused
      during the clamping through the arterial catheter for 4 hours, 60 minutes after
      the beginning of clamping Ci 3-3H-glucose was infused through the venous catheter
      till the end of clamping, 120 minutes after the beginning of clamping insulin and
      25% glucose were infused for 2 hours with the blood sugar remaining at about 5
      mmol/L) and control group (normal saline were infused). Before and after clamping
      venous blood was collected to detect the concentration of ghrelin. At the time
      points 0, 120, 200, 230, and 240 min specimens of plasma were collected to detect
      the concentrations of blood sugar, insulin, free fatty acid, and 3-3H glucose
      activity. RESULTS: 120 minutes after the beginning of hyperinsulinaemic
      euglycaemic clamping the plasma FFA was significant increased from 742 micromol/L
      +/- 51 micromol/L to 2346 micromol/L +/- 238 micromol/L (P < 0.01) in the lipid
      infused group. The glucose infusion rate (GIR) in the lipid-infused rats,
      compared to the control rats, was significantly reduced by 35% (200-240 min
      after, with an average value of 12.6 mg.kg(-1).min(-1) +/- 1.5 mg.kg(-1).min(-1)
      vs. 34.0 mg.kg(-1).min(-1) +/- 1.6 mg.kg(-1).min(-1), P < 0.01). By the end of
      clamping (240 min after) the GIR in the lipid-infused group was 12.0 mg.kg(
      1).min(-1) +/- 1.9 mg.kg(-1).min(-1), significantly lower than that in the
      control group (34.7 mg.kg(-1).min(-1) +/- 1.7 mg.kg(-1).min(-1), P < 0.01). At
      the end of clamping, the hepatic glucose production (HGP) in the controls rats
      was significantly suppressed by 88% (from 19.0 mg.kg(-1).min(-1) +/- 4.5 mg.kg(
      1).min(-1) to 2.3 mg.kg(-1).min(-1) +/- 0.9 mg.kg(-1).min(-1), P < 0.01). The
      suppressive effect of insulin on HGP was significantly blunted in the lipid
      infused rats (200 - 240 min: from 18.7 mg.kg(-1).min(-1) +/- 3.0 mg.kg(-1).min(
      1) to 23.2 mg.kg(-1).min(-1) +/- 3.1 mg.kg(-1).min(-1), P < 0.05). At the end of
      euglycemic-hyperinsulinemic clamping the plasma ghrelin levels in the controls
      was significantly decreased as compared with the basal level (584 ng/L +/- 67
      ng/L vs. 892 ng/L +/- 90 ng/L, P < 0.05). Lipid infusion of 4 hours also caused a
      significant decrease in plasma ghrelin concentration in comparison with the basal
      levels (548 ng/L +/- 82 ng/L vs. 936 ng/L +/- 78 ng/L, P < 0.05). At the end of
      euglycemic-hyperinsulinemic clamping, there was no significant difference in the
      plasma ghrelin levels between the control and lipid-infused rats (584 ng/L +/- 67
      ng/L vs. 548 ng/L +/- 82 ng/L, P > 0.05). Pearson analysis showed that fasting
      plasma ghrelin concentration was negatively correlated with fasting plasma
      insulin levels (r = -0.52, P < 0.05)and blood glucose (r = -0.61, P < 0.05).
      CONCLUSION: Lipid-infusion impairs the ability of insulin to suppress lipolysis
      and hepatic glucose output, as well as insulin-mediated glucose utilization in
      peripheral tissue. Euglycemic-hyperinsulinemic clamping decreases the circulating
      ghrelin level in rats, but an acute insulin resistance induced by lipid-infusion
      in vivo has no effect on circulating ghrelin level.

PMID- 15569463
TI  - [The biological characteristics of a mucoid Pseudomonas aeruginosa strain with a
      newly discovered mutation of mucA gene].
AB  - OBJECTIVE: To compare the mucA gene sequence, biofilm formation, growth rate and
      antibiotic resistance of a mucoid Pseudomonas aeruginosa strain 'PA17' with those
      of the nonmucoid strain PAOI. METHODS: The mucA genes of PA17 and PAOI were
      amplified and the PCR products were sequenced. Biofilm was established and
      detected with scanning electron microscope 8 h, 24 h, 3 d and 6 d later. Clones
      counting method was used to compare the growth curves of PA17 and PAOI.
      International standard plate dilution method was used to detect the
      susceptibility of common antibiotics for PA17 and PAOI in vitro. RESULTS: There
      was a 166-333 deletion mutation in mucA gene of PA17. The biofilm formation rate
      and growth rate of PA17 were noticeably lower than those of PAOI. The antibiotic
      resistance profile of PA17 was identical to that of PAOI. CONCLUSION: A mucoid
      Pseudomonas aeruginosa with a new type of mutation of mucA gene is discovered.
      The biologic characteristics of this strain are different from those of the
      mucoid Pseudomonas aeruginosa strain reported previously, which may be related
      with the newly discovered mutation of mucA gene.

PMID- 15569464
TI  - [Effects of nitric oxide donor on autoimmune myasthenia gravis in rats].

PMID- 15569465
TI  - [Detection and purification of cytokine-secretion T lymphocytes in homologous
      transplantation reaction].

PMID- 15569466
TI  - [Syncope, vomiting, hypotension, kidney dysfunction, heart arrest-- a case
      report].

PMID- 15569467
TI  - [Treatment of idiopathic thrombocytopenic purpura in pregnancy using method of
      evidence-based medicine].

PMID- 15569468
TI  - [Specific characteristic of X-ray changes in Klebsiella pneumonia ].

PMID- 15569469
TI  - [Cost effectiveness analysis of oseltamivir phosphorus in the treatment of
      influenza].

PMID- 15569471
TI  - [6th International Breast Cancer Congress held in Italy].

PMID- 15569472
TI  - Serum adiponectin level in patients with obstructive sleep apnea hypopnea
      syndrome.
AB  - BACKGROUND: Adiponectin, secreted by adipocytes, has been found to be associated
      with diabetes, obesity and some cardiovascular diseases. Obstructive sleep apnea
      hypopnea syndrome (OSAHS) is also closely related to obesity and easily
      complicated with diabetes and some cardiovascular diseases. This study was
      carried out to explore the change of serum adiponectin level in patients with
      OSAHS. METHODS: Polysomnography was performed in 71 patients with OSAHS (OSAHS
      group) and 26 simple obese controls (control group). The two groups had no
      significant difference in age and body mass index (BMI). Radioimmunoassy was used
      to test serum adiponectin level. RESULTS: Serum adiponectin level was
      significantly lower in OSAHS group [(5.03 +/- 1.01) mg/L] than that in the
      control group [(7.09 +/- 1.29) mg/L, P < 0.05]. The differences between two
      groups were independent of gender. In OSAHS groups, serum adiponectin levels were
      negatively correlated with apnea hypopnea index (AHI) (r = -0.78, P < 0.01), BMI
      (r = -0.13, P < 0.05), waist circumference (r = -0.36, P < 0.01), and neck
      circumference (r = -0.42, P < 0.01), but positively correlated with the minimal
      pulse oxyhemoglobin saturation (r = 0.48, P < 0.01). CONCLUSION: OSAHS may
      contribute to the decrease of serum adiponectin level independent of obesity.

PMID- 15569473
TI  - Clinical benefit of gemcitabine plus cisplatin 3-week regimen for patients with
      advanced non-small cell lung cancer: a prospective observational study.
AB  - BACKGROUND: Platinum-based chemotherapy has been proved effective in patients
      with advanced non-small cell lung cancer (NSCLC). This study evaluated the
      effectiveness and safety of first-line chemotherapy with gemcitabine plus
      cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with
      advanced NSCLC. METHODS: Two hundred and twenty-one patients with NSCLC stage
      IIIb or IV were enrolled and 209 were eligible for effectiveness and safety
      analysis. The median age was 58 (range 29 to 79) years. The percents of cases in
      stage IV and stage IIIb were 52.2% and 47.8%; of Karnofsky performance score
      (KPS) less than 80 and 80 - 100 were 37.3% and 62.7% and of adeno-cancer and non
      adeno-cancer were 59.8% and 40.2%. The average number of completed chemotherapy
      cycles was three. Measures of effectiveness included clinical benefit,
      significant clinical response (SCR) and adverse effects of GEM-Cis in the
      treatment of NSCLC at stages IIIb/IV. RESULTS: KPS increased from 79 +/- 9 at
      baseline to 86 +/- 10 after chemotherapy (P < 0.01). Lung cancer symptom scale
      (LCSS) score of pain, dyspnea and cough increased from 77 +/- 24, 74 +/- 22 and
      63 +/- 19 to 92 +/- 15, 90 +/- 14 and 86 +/- 15, respectively (P < 0.01). The
      clinical benefit rate was 85.2% [95% confidence interval (CI) 80.3% - 90.0%]. The
      SCR was 89.5% (95% CI 85.3% - 93.7%). Median survival time was 7.8 months (95% CI
      7.1 months-9.1 months). Sixty-four patients (30.6%) experienced an adverse effect
      that was deemed clinically significant. Only one patient (0.5%) was hospitalized
      due to chemotherapy related adverse effects. Life-threatening toxicity was
      observed in two patients (1.0%). CONCLUSION: First-line chemotherapy with GEM-Cis
      in the routine care of Chinese patients with advanced NSCLC is effective and
      safe.

PMID- 15569474
TI  - Pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease and
      therapeutic effects of glucocorticoids and N-acetylcysteine in rats.
AB  - BACKGROUND: T lymphocytes and matrix metalloproteinase (MMP) play an important
      role in the pathogenesis of chronic obstructive pulmonary disease (COPD).
      However, the details of the mechanisms involved are unclear. The aims of this
      study were to investigate the changes in interferon-gamma (IFN-gamma),
      interleukin-4 (IL-4), MMP-9, MMP-12 and tissue inhibitor of metalloproteinase-1
      (TIMP-1) levels in a smoke-induced COPD rat model and the therapeutic effects of
      glucocorticoids and N-acetylcysteine. METHODS: Male Wistar rats were exposed to
      cigarette smoke for 3.5 months. Budesonide or N-acetylcysteine was given in the
      last month. Lung function was measured at the end of the study. IL-4 and IFN
      gamma levels were then determined in bronchoalveolar lavage fluid and lung tissue
      samples by enzyme-linked immunosorbent assay. The expression of MMP-9, MMP-12 and
      TIMP-1 mRNA in lung tissue was determined by RT-PCR. RESULTS: In comparison with
      the control group, rats exposed to smoke had a significant increase in IL-4 and
      MMP-12 levels and a significant decrease in IFN-gamma levels. In addition, the IL
      4/IFN-gamma ratio and MMP-12/TIMP-1 ratio were both higher. At the same time, the
      ratio of forced expiratory volume in 0.3 second to forced vital capacity
      (FEV(0.3)/FVC) and dynamic compliance (C(dyn)) decreased and expiratory
      resistance (Re) increased. By measuring pulmonary mean linear intercept and mean
      alveolar numbers, obvious emphysematous changes were observed in the smoke
      exposed group. After treatment with budesonide, IL-4 and MMP-12 decreased and IFN
      gamma increased. The IL-4/IFN-gamma ratio returned to normal, though the MMP
      12/TIMP-1 ratio remained unchanged. FEV(0.3)/FVC was significantly higher and Re
      was significantly lower than that in untreated smoke exposed rats. No significant
      differences were found in pulmonary mean linear intercept and mean alveolar
      numbers. After treatment with N-acetylcysteine, IFN-gamma increased and the IL
      4/IFN-gamma ratio decreased. The MMP-12/TIMP-1 ratio remained unchanged. Re and
      C(dyn) both improved obviously. No significant differences were found in
      pulmonary mean linear intercept and mean alveolar numbers. Correlation analysis
      indicated that IL-4 levels in lung tissue correlated negatively with FEV(0.3)/FVC
      (r = -0.53, P = 0.001), IFN-gamma levels in lung tissue correlated negatively
      with Re (r = -0.63, P = 0.000) and positively with C(dyn) (r = 0.44, P = 0.009),
      and that the IL-4/IFN-gamma ratio correlated negatively with FEV(0.3)/FVC (r = 
      0.44, P = 0.010) and C(dyn) (r = -0.42, P = 0.015) and positively with Re (r =
      0.58, P = 0.000). Finally, MMP-12 correlated negatively with FEV(0.3)/FVC (r = 
      0.36, P = 0.026). CONCLUSIONS: Cigarette smoke exposure increases IL-4 levels and
      decreases IFN-gamma levels. This may be the result of smoke-induced changes in
      lung function. Budesonide can mitigate the changes in IL-4 and IFN-gamma levels
      induced by smoke exposure. N-acetylcysteine has no effect on IL-4, but increases
      IFN-gamma levels and brings the IL-4/IFN-gamma ratio back to normal. Cigarette
      smoke can also promote MMP-12 gene expression and elevate the MMP-12/TIMP-1
      ratio. This effect may play a role in smoke-induced emphysema. Budesonide and N
      acetylcysteine do not alter the MMP-12/TIMP-1 ratio in this study when given in
      the late phase of smoke exposure.

PMID- 15569475
TI  - Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs
      sensitized and challenged with ovalbumin.
AB  - BACKGROUND: There is currently considerable interest in the potential value of
      selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of
      asthma. However, whether they influence eosinophilic airway inflammation
      associated cough remains unclear. The objective of this study was to investigate
      the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response
      and airway inflammation in guinea pigs sensitized and challenged with ovalbumin.
      METHODS: Forty sensitized guinea pigs were randomly divided into four groups:
      control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n =
      10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later,
      animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499
      or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and
      25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and
      airway responsiveness to methacholine inducing a 150% of the peak airway pressure
      to the baseline (PC150) was measured. Finally, total cell number and
      differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough
      frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3
      minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/
      2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P < 0.05,
      respectively). The injection of 25 mg/kg SB207499 significantly inhibited the
      increased cough response and airway hyperresponsiveness, the cough frequency and
      PC150 in guinea pigs were (13 +/- 2) times/3 minutes and (680 +/- 81) microg/ml
      (P < 0.05), which differed significantly from (18 +/- 2) times/3 minutes and (400
      +/- 86) microg/ml after the administration of the same dose of aminophylline (P <
      0.05). The inhibition of SB207499 on cough response was dose-dependent.
      Similarly, SB207499 decreased the total cell number and percentage of eosinophils
      in bronchoalveolar lavage fluid to (2.1 +/- 0.5) x 10(6)/ml and (20 +/- 5)%
      respectively, which were significantly different from (3.2 +/- 0.5) x 10(6)/ml
      and (29 +/- 5)% in the aminophylline group (P < 0.05, respectively) or (4.2 +/-
      0.7) x 10(6)/ml and (35 +/- 4)% in the challenge group (P < 0.05, respectively).
      CONCLUSION: Phosphodiesterase 4 inhibitor may be more useful than aminophylline
      for cough associated with eosinophilic airway inflammation via inhibiting airway
      inflammation and airway hyperresponsiveness.

PMID- 15569476
TI  - Humoral immune responses in rabbits induced by an experimental inactivated severe
      acute respiratory syndrome coronavirus vaccine prepared from F69 strain.
AB  - BACKGROUND: The etiologic agent of severe acute respiratory syndrome (SARS) has
      been confirmed to be a novel coronavirus (CoV), namely SARS-CoV. Developing safe
      and effective SARS-CoV vaccines is essential for us to prevent the possible
      reemergence of its epidemic. Previous experiences indicate that inactivated
      vaccine is conventional and more hopeful to be successfully developed.
      Immunogenicity evaluation of an experimental inactivated SARS-CoV vaccine in
      rabbits was conducted and reported in this paper. METHODS: The large-scale
      cultured SARS-CoV F69 strain was inactivated with 0.4% formaldehyde and purified,
      then used as the immunogen combined with Freund's adjuvant. Eight adult New
      Zealand rabbits were immunized four times with this experimental inactivated
      vaccine. Twelve sets of rabbit serum were sampled from the third day to the
      seventy-fourth day after the first vaccination. The titers of specific anti-SARS
      CoV IgG antibody were determined by indirect enzyme-linked immunosorbent assay,
      and the neutralizing antibody titers were detected with micro-cytopathic effect
      neutralization test. RESULTS: Rapid and potent humoral immune responses were
      induced by the inactivated SARS-CoV vaccine in all the eight test rabbits. Titers
      of both specific IgG antibody and neutralizing antibody peaked at about six weeks
      after first vaccination, with the maximum value of 1:81 920 and 1:20 480,
      respectively. After that, serum antibody levels remained at a plateau or had a
      slight decrease, though two boosters were given in the succedent 4 to 5 weeks.
      Cross neutralization response existed between SARS-CoV F69 strain and Z2-Y3
      strain. CONCLUSIONS: The inactivated SARS-CoV vaccine made from F69 strain owns
      strong immunogenicity, and the cross neutralization response between the two
      different SARS-CoV strains gives a hint of the similar neutralizing epitopes,
      which provide stable bases for the development of inactivated SARS-CoV vaccines.

PMID- 15569477
TI  - Effect of passive sensitization by serum from allergic asthmatic patients on the
      activity and expression of voltage-dependent delayed rectifier potassium channel
      in human bronchial smooth muscle cells.
AB  - BACKGROUND: Potassium (K+) channels are important in regulating cell membrane
      potential and excitability. Although bronchial myocytes from asthmatic rats show
      a significant reduction in voltage-dependent delayed rectifier potassium channel
      (Kv) current density and higher excitability, the activity and expression of Kv
      in human bronchial smooth muscle cells (HBSMCs) have never been studied. The
      objective of this study was to investigate the effect of passive sensitization by
      asthmatic serum on the activity of Kv and the expression of Kv isoform Kv1.5 in
      HBSMCs. METHODS: HBSMCs were randomly divided into two groups: control group
      (containing 10% serum from nonatopic individuals) and sensitized group
      (containing 10% asthmatic serum), then cultured for 24 hours. Whole-cell patch
      clamp, immunofluorescence staining, reverse transcription-polymerase chain
      reaction and Western blot techniques were used to study the effect of passive
      sensitization on the activity of Kv and the expression of Kv1.5 in HBSMCs.
      RESULTS: The membrane potential in passively sensitized HBSMCs was significantly
      depolarized to -(26.7 +/- 5.2) mV compared with -(41.3 +/- 6.4) mV in the control
      group (P < 0.01). Passive sensitization caused a significant inhibition of Kv
      currents in HBSMCs, resulting in a downward shift in the current-voltage (I-V)
      relationship curve. At +50 mV, the peak Kv current density of passively
      sensitized HBSMCs was significantly decreased from (54.6 +/- 8.7) picoamperes per
      picofarad (pA/pF) to (32.1 +/- 7.1) pA/pF (P < 0.01). The expression level of
      Kv1.5 mRNA in passively sensitized HBSMCs was significantly lower than that in
      the control group (0.76 +/- 0.07 vs 1.04 +/- 0.13, P < 0.05). The expression of
      Kv1.5 protein of passively sensitized HBSMCs was also significantly reduced
      compared to that from the control group (984 +/- 168 vs 2200 +/- 380, P < 0.05).
      CONCLUSIONS: The activity and expression of Kv were all decreased in HBSMCs
      passively sensitized by asthmatic serum compared with nonsensitized cells. These
      changes might be involved in the mechanisms of formation and development of
      asthma.

PMID- 15569478
TI  - Correlation of HDEFB1 polymorphism and susceptibility to chronic obstructive
      pulmonary disease in Chinese Han population.
AB  - BACKGROUND: Inherited factors are involved in the development of chronic
      obstructive pulmonary disease (COPD). This study was designed to investigate the
      relationship between polymorphisms of HDEFB1 668 C/G and 1654G/A loci and
      susceptibility to COPD in Chinese Han population. METHODS: After the process of
      extracting genomic DNA from peripheral blood of COPD smokers and healthy smokers,
      the loci of genotypes 668C/G and 1654G/A were determined by polymerase chain
      reaction-restriction fragment length polymorphism analysis and polymerase chain
      reaction-single strand conformation polymorphism analysis. RESULTS: With respect
      to HDEFB1 668 locus, the occurences of CC, CG, GG genotypes were 72.7%, 25.0%,
      2.3% in COPD smokers and 53.2%, 38.3%, 8.5% in healthy smokers (P < 0.05,
      respectively). The allele frequencies of 668 C and 668G were 85.2% and 14.8% in
      COPD smokers and 72.3% and 27.7% in healthy smokers (P < 0.01, respectively, odds
      ratio was 2.32 with 95% confidence interval 1.37 to 3.72). As to HDEFB1 1654G/A
      locus, neither genotype distribution difference nor allele distribution
      difference was found when comparing COPD smokers with healthy smokers.
      CONCLUSION: The polymorphism of HDEFB1 668C/G is associated with susceptibility
      to COPD in Chinese Han population; furthermore, the 668G allele represents
      relatively lower susceptibility to COPD.

PMID- 15569479
TI  - Effect of antisense RNA targeting polo-like kinase 1 on cell cycle and
      proliferation in A549 cells.
AB  - BACKGROUND: Expression of polo-like kinase 1 (Plk1) is elevated in lung cancer
      and has been proposed as having prognostic value and related to resistance to
      chemotherapy and radiation. In addition, Plk1 has several functions in mitotic
      progression. In this study, the authors investigated the effect of Plk1 depletion
      on cell cycle progression and proliferation in A549 cells, a lung cancer cell
      line. METHODS: A recombinant plasmid containing antisense RNA targeting Plk1
      (pcDNA3-Plk1) was transfected into A549 cells. Reverse transcription-polymerase
      chain reaction and Western blot were used to examine Plk1 gene expression. Cell
      proliferation was evaluated by direct cell counting and bromodeoxyuridine (BrdU)
      labelling. Cell cycle and apoptosis were examined by flow cytometry. Expression
      of alpha-tubulin was detected by immunofluorescence, and the inhibition rate (IR)
      by chemotherapeutic agents was determined by 3-(4,5-dimethylthiazol-2-yl) 2,5
      diphenyl-tetrazolium bromide assay. RESULTS: After transfection into A549 cells,
      pcDNA3-Plk1 reduced Plk1 mRNA by 46.75% for 24 hours and by 61.84% for 48 hours.
      Plk1 protein was significantly decreased simultaneously (P < 0.05). Abnormal
      morphological changes of cells and growth inhibition were observed in pcDNA3-Plk1
      transfected groups. The BrdU labelling index was 25.59% 48 hours after
      transfection, which was significantly lower than that of the control groups (P <
      0.05). Forty-eight hours after transfection, there showed absence of microtubule
      polymerization and spindle abnormalities in staining for alpha-tubulin. A549
      cells showed a strong G2/M arrest and apoptosis 72 hours post transfection. IR of
      vinorelbine in pcDNA3-Plk1 transfected groups was significantly higher than that
      of the other groups (P < 0.05, respectively). CONCLUSIONS: Plk1 depletion
      interferes with spindle formation, induces cell cycle arrest and apoptosis, and
      consequently inhibits cell proliferation in A549 cells. Moreover, it sensitizes
      lung cancer cells to chemotherapy.

PMID- 15569480
TI  - Effect of homocysteine on plaque formation and oxidative stress in patients with
      acute coronary syndromes.
AB  - BACKGROUND: Cardiovascular diseases, especially coronary artery disease (CAD),
      are major causes of death in industrialized countries. Elevated concentrations of
      plasma homocysteine (Hcy) have been associated with an increased risk of CAD.
      Increased plasma levels of chemokine, characterized by their ability to induce
      migration and activation of leukocytes, may contribute to the pathogenesis of
      CAD. This study was designed to investigate the changes of plasma Hcy, monocyte
      chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary
      syndrome patients. METHODS: A total of 149 subjects were divided into four
      groups: 50 patients with unstable angina, 30 patients with acute myocardial
      infarction, 20 coronary restenosis patients after percutaneous coronary
      intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1,
      malondialdehyde and superoxide dismutase were measured. RESULTS: Plasma levels of
      Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial
      infarction and restenosis patients compared with control subjects (P < 0.05,
      respectively). Plasma levels of malondialdehyde were significantly increased in
      unstable angina and acute myocardial infarction patients when compared with
      control subjects (P < 0.05, respectively). Plasma superoxide dismutase levels
      were significantly reduced in acute myocardial infarction patients when compared
      with control group (P < 0.01). CONCLUSION: Hcy might act as an atherogenic factor
      through promoting chemokine, reactive oxygen species and oxidized low density
      lipoprotein production and thereby convert a stable plaque into an unstable
      potentially occlusive lesion.

PMID- 15569481
TI  - Diagnosis of isolated dextrocardia using angiocardiography or surgery.
AB  - BACKGROUND: Isolated dextrocardia is a rare phenomenon and usually associated
      with multiple cardiac anomalies. This study was to evaluate the accuracy of
      diagnosis of isolated dextrocardia by using angiocardiography and to compare it
      with the results of surgery. METHODS: The clinical data of 27 cases of congenital
      isolated dextrocardia were collected to understand the diagnostic approaches to
      the major cardiac anomalies. All cases underwent angiocardiography followed by
      palliative or curative surgery. The diagnosis was compared by angiocardiography
      relying on segmental analysis with the pathological features observed in surgery.
      RESULTS: The results of angiocardiography of 22 patients were the same as the
      pathological features observed during surgery, including one case with congenital
      left ventricular diverticulum was inadvertently omitted in angiocardiograhy.
      There were significantly dissimilar diagnoses between angiocardiograhy and post
      operation in 5 patients, including anatomical corrected transposition of great
      arteries misinterpreted as corrected transposition of the great arteries in 1,
      complete transposition of great arteries misinterpreted as corrected
      transposition of the great arteries in 1, single ventricle misinterpreted as
      double-outlet right ventricle in 1, and anatomical double-outlet left ventricle
      misinterpreted as corrected transposition of the great arteries in 2.
      Misdiagnostic rate of angiocardiograhy was almost 20%. CONCLUSIONS:
      Angiocardiography is of great significance in the diagnosis and classification of
      isolated dextrocardia. However, because of the intricacy of cardiac anomalies of
      isolated dextrocardia, atrial angiography and double oblique projection are
      needed to improve the accuracy of diagnosis to support surgical treatments.

PMID- 15569482
TI  - Influence of an intravenous infusion of amino acids and glucose on the pancreatic
      exocrine in rats.
AB  - BACKGROUND: A number of reports based on both animal experiments and clinical
      investigations have pointed out that total parenteral nutrition (TPN) suppresses
      the function of the exocrine pancreas. Even though pancreatic hypotrophy and
      dysfunction resulting from TPN may be explained by several mechanisms, the
      clinically most important cause is that nutrients in circulation affect
      pancreatic secretion. The effect of nutrients on the exocrine pancreas is still
      controversial. The aim of the present study was, therefore, to clarify the
      influence of intravenous amino acids and hypertonic glucose in TPN solution on
      the exocrine pancreas. METHODS: Three mixed TPN solutions, consisting of 30% or
      50% glucose or of 14% amino acids, were employed. Twenty-four male Sprague-Dawley
      rats were randomly divided into four groups, six rats in each group, including a
      control group and one group receiving each of the three TPN solutions. All
      animals were killed after 10 days of TPN. Body weight, pancreatic content, and
      enzyme levels in the pancreas were measured. RESULTS: Compared with the control
      group, pancreatic wet weight was lower in all TPN groups. Glucose significantly
      decreased the content and concentration of pancreatic protein, but amino acids
      did not alter the concentration of protein. The level of amylase was lower in all
      parenterally fed groups, with a greater decrease in the groups treated with amino
      acids and 30% glucose than with 50% glucose. Trypsin levels in all groups
      receiving TPN were markedly higher than in the control group. CONCLUSION: TPN
      results in atrophy of the pancreas, but trypsin levels increase with TPN
      treatment. Glucose elevates the amylase level in the pancreas, while amino acids
      suppress pancreatic amylase. Amino acids used as a source of protein maintain
      normal pancreatic protein levels.

PMID- 15569483
TI  - Relationship between somatostatin receptors and activation of hepatic stellate
      cells.
AB  - BACKGROUND: Somafostatin receptors (SSTRs) have been suggested to involve in
      mediating the effect of somatostatin on hepatic stellate cells (HSCs) in an
      activation-dependent way. We, therefore, try to investigate the relationship
      between expression of SSTRs and activation of rat HSCs. METHODS: HSCs were
      isolated from rats by in situ perfusion and single-step density gradient
      centrifugation. SSTR1-5 mRNA levels in the differentiated first passage HSCs were
      detected by means of a reverse transcription polymerase chain reaction. On the
      other hand, hepatic fibrosis was induced in adult male Sprague-Dawley rats by
      carbon tetrachloride intoxication, and the expression of SSTR1-5 in normal as
      well as fibrotic livers was measured by immunohistochemical staining. RESULTS:
      SSTR mRNA and SSTR could not be found in freshly isolated rat HSCs or normal rat
      liver. However, SSTR1-3 mRNA appeared as HSCs became wholly activated, and could
      also be identified on the membrane of activated HSCs in the perisinusoid space,
      fibrous septa, etc. CONCLUSION: The expression of SSTR1-3 in the rat HSC is
      closely related to its activation. This may reflect one of the main negative
      regulation mechanisms in the course of HSC activation.

PMID- 15569484
TI  - Single nucleotide polymorphisms of deoxyribonuclease I and their expression in
      Chinese systemic lupus erythematosus patients.
AB  - BACKGROUND: Previous studies have suggested that interrupted clearance of nuclear
      DNA-protein complexes after cell death might initiate and propagate systemic
      lupus erythematosus (SLE). Deoxyribonuclease I (DNaseI) may be responsible for
      the removal of DNA from nuclear antigens at sites of high cell turnover, thus
      preventing the onset of SLE. The purpose of this study was to genotype the single
      nucleotide polymorphisms (SNPs) of DNase1 and characterize its gene expression
      and alternatively spliced transcripts in Chinese patients with SLE in order to
      understand the pathogenic role of DNase1 in human SLE. METHODS: Four SNPs located
      at the 3' end of the DNase1 gene, as listed on the SNP website, were selected for
      analysis. Those SNPs with relatively high heterozygosity were chosen for
      genotyping in 312 Chinese SLE families using the Taqman minor groove binder (MGB)
      allelic discrimination method. Haplotypes were constructed and linkage
      disequilibrium tests were performed using GeneHunter. DNase1 mRNA expression was
      detected using real-time polymerase chain reaction (PCR), and alternatively
      spliced transcripts were isolated using capillary electrophoresis. Any effects
      the specific SNP haplotypes had on DNase1 gene expression and the alternatively
      spliced transcripts were also assessed. RESULTS: rs179982 and rs1053874 had high
      heterozygosity, about 0.5 in this Chinese cohort, while rs1059857 was also found
      to be heterozygous. Analysis of the haplotype combining rs179982-rs1030874 (C-G)
      and rs179982-rs1030874-rs1059857 (C-G-G) revealed a skewed transmission in favor
      of affected offspring. DNase1 gene expression was higher in SLE patients than in
      normal controls (P < 0.001), but this was not related to disease activity or SNP
      haplotype. Capillary electrophoresis revealed that the pattern of alternatively
      spliced transcripts in patients differed from that of normal controls.
      Furthermore, different SNP haplotype combinations generated different transcript
      patterns in SLE patients. CONCLUSIONS: The SNP haplotypes are in linkage
      disequilibrium in Chinese SLE patients and may induce the disease through a
      modification of DNase1 mRNA splicing rather than at the level of mRNA expression.
      There is a relatively unique transcript band in SLE patients independent of
      special haplotype, which suggests that other unknown factors might be involved in
      adjusting gene expression.

PMID- 15569485
TI  - Effect of thrombin on blood brain barrier permeability and its mechanism.
AB  - BACKGROUND: Previous studies have indicated that thrombin (TM) may play a major
      role in brain edema after intracerebral hemorrhages (ICHs). However, the
      mechanism of TM-induced brain edema is poorly understood. In this study, we
      explored the effect of TM on the permeability of the blood brain barrier (BBB)
      and investigated its possible mechanism, aiming at providing a potential target
      for brain edema therapy after ICHs. METHODS: TM or TM + cathepsin G (CATG) was
      stereotaxically injected into the right caudate nucleus of Sprague-Dawley rats in
      vivo. BBB permeability was measured by Evans-Blue extravasation. Brain water
      content was determined by the dry-wet weight method. Brain microvascular
      endothelial cells were then cultured in vitro. After TM or TM + CATG was added to
      the endothelial cell medium, changes in the morphology of cells were dynamically
      observed by phase-contrast light microscopy, and the expression of matrix
      metalloproteinase-2 (MMP-2) protein was measured by immunohistochemical method.
      RESULTS: BBB permeability increased at 6 hours after a TM injection into the
      ipsilateral caudate nucleus (P < 0.05), peaked between 24 hours (P < 0.01) and 48
      hours (P < 0.05) after the injection, and then declined. Brain water content
      changed in parallel with the changes in BBB permeability. However, at all time
      points, BBB permeability and brain water content after a TM + CATG injection were
      not significantly different from the respective parameters in the control group
      (P > 0.05). TM induced endothelial cell contraction in vitro in a time-dependent
      manner and enhanced the expression of MMP-2 protein. After incubation with TM +
      CATG, cell morphology and MMP-2 expression did not change significantly as
      compared to the control group (P > 0.05). CONCLUSIONS: Increased BBB permeability
      may be one of the mechanisms behind TM-induced cerebral edema. TM induces
      endothelial cell contraction and promotes MMP-2 expression by activating protease
      activated receptor-1 (PAR-1), possibly leading to the opening of the BBB.

PMID- 15569486
TI  - Antiepileptic drug-induced multidrug resistance P-glycoprotein overexpression in
      astrocytes cultured from rat brains.
AB  - BACKGROUND: Intractable epilepsy may be due to multidrug resistance induced by
      conventional antiepileptic drugs. The phenomenon is sometimes associated with an
      overexpression of multidrug resistance gene 1 (MDR1). The purpose of this study
      was to determine if the overexpression of MDR1 could be induced in astrocytes
      from rat brains in vitro using antiepileptic drugs. METHODS: Astrocyte cell
      cultures from postnatal Wistar rats (within 24 hours of birth) were established.
      Different concentrations of the antiepileptic drugs phenytoin, phenobarbital,
      carbamazepine, and valproic acid were added to the cultures for 10, 20, or 30
      days. The expression of P-glycoprotein (Pgp), the protein product of MDR1, was
      investigated with immunocytochemistry. RESULTS: Less than 5% of normal, untreated
      astrocytes had detectable Pgp staining at any time point. Phenytoin,
      phenobarbital, carbamazepine, and valproic acid induced the overexpression of Pgp
      in astrocytes in a dose- and time-dependent manner. Significantly higher levels
      of Pgp staining were detected at therapeutic concentrations of certain
      antiepileptic drugs (20 microg/ml phenobarbital, 40 microg/ml phenobarbital, and
      20 microg/ml phenytoin) on day 30. Upregulation of Pgp was detected when using
      higher concentrations of phenytoin, phenobarbital, and valproic acid on day 20
      and when using higher concentrations of any of the four antiepileptic drugs on
      day 30. CONCLUSIONS: Treatment with antiepileptic drugs may contribute to the
      overexpression in astrocytes of MDR1 and its protein product, Pgp. The mechanism
      leading to MDR must be considered in patients undergoing long-term treatment with
      antiepileptic drugs.

PMID- 15569487
TI  - Function of Delta4 gene and its effects on 32D cell differentiation.
AB  - BACKGROUND: Notch activation leads to transcriptional suppression of lineage
      specific genes, inhibiting differentiation in response to inductive signals. The
      Notch signal system contains three parts: Notch molecules, Notch ligands and
      effectors. Delta4 is a newly-discovered Notch ligand which has received the
      attention of few detailed studies. This study sought to explore the biological
      function of Delta4 and observe its effects on 32D cell differentiation. METHODS:
      Delta4-expressing vector pTracer.CMV.Delta4.FLAG was constructed using molecular
      biological techniques. CHO cells stably transfected with pTracer.CMV.Delta4.FLAG
      were confirmed to have a Delta4 protein band via Western blotting. High
      expression Delta4-CHO clones were selected for the following functional studies.
      Notch1-CHO and Notch2-CHO were used as host cells. After transiently transfecting
      with transition protein 1 (TP1), Delta4 activity was compared in both cell lines
      by means of luciferase analysis. CHO cells were incubated with Notch1-32D cells
      that had been transfected with Notch1 and were observed for granulocyte colony
      stimulating factor (G-CSF)-induced differentiation. Jagged2-CHO and Delta4-CHO
      cells transfected with the Notch ligands Jagged2 and Delta4, respectively, were
      incubated with Notch1-32D cells to observed inhibition of Notch on G-CSF-induced
      differentiation. RESULTS: The vector pTracer.CMV.Delta4.FLAG was constructed
      successfully. CHO cells were stably transfected with the vector
      pTracer.CMV.Delta4.FLAG. Two CHO cell lines expressing Delta4 at high levels were
      selected for use in the study. Delta4 was found to induce signal activity via
      both Notch1 and Notch2 and the induction of signaling activity was stronger in
      Notch2 cells than in Notch1 cells. Compared with other Notch ligands, Delta4 was
      slightly weaker than Jagged2, but stronger than Delta1 and Jagged1 in terms of
      Notch1 ligands. In terms of Notch2, Delta4 had a strong signaling activity, but
      was weaker than Delta1, Jagged1, and Jagged2. Jagged2 could inhibit Notch1-32D
      cell differentiation induced by G-CSF, but Delta4 could not. CONCLUSIONS: Delta4
      induces both Notch1 and Notch2 activity and is a ligand for both of them. The
      effect of Delta4 is stronger on Notch2 than that on Notch1. Jagged2 can inhibit
      Notch1-32D cell differentiation induced by G-CSF, but Delta4 cannot.

PMID- 15569488
TI  - Effects of Shuanghuangbu on the total protein content and ultrastructure in
      cultured human periodontal ligament cells.
AB  - BACKGROUND: Successful periodontal regeneration depends on the migration,
      proliferation and differentiation of periodontal ligament cells in periodontal
      defects. The total protein content and the ultrastructure demonstrate the
      metabolizability and activity of periodontal ligament cells. This study was
      conducted to observe the effects of Shuanghuangbu, a mixture of medicinal herbs,
      on the total protein content and the ultrastructure of human periodontal ligament
      cells. METHODS: Periodontal ligament cells were grown to confluence and then
      cultured in Dulbecco's modified eagle medium (DMEM) supplemented with
      Shuanghuangbu over the concentration range of 0 to 1000 microg/ml. The total
      protein content in cultured cells was determined by using Coommasie brilliant
      blue technique. Periodontal ligament cells were incubated in 0 and 100 microg/ml
      Shuanghuangbu decoction for 5 days, then observed through transmission electron
      microscope. RESULTS: The total protein content of human periodontal ligament
      cells increased in each experiment group added 10 - 1000 microg/ml Shuanghuangbu
      respectively, and the effect of 100 microg/ml was excellent. Under the
      transmission electron microscope, there were more rough endoplasmic reticulums
      and mitochodrias in the experiment group than those in the control group.
      CONCLUSION: Shuanghuangbu stimulates the protein synthesis of human periodontal
      ligament cells and improves human periodontal ligament cells' metabolizability
      and activity.

PMID- 15569489
TI  - Schistosoma japonicum: construction of phage display antibody library and its
      application in the immunodiagnosis of infection.
AB  - BACKGROUND: A monoclonal antibody would be an effective tool for the detection of
      circulating antigens in the serum of patients with schistosomiasis, but the
      traditional way of producing monoclonal antibodies is not cost-effective. The
      objective of this study was to find a new method for the large-scale production
      of monoclonal antibodies against Schistosoma japonicum (Sj). METHODS: A phage
      display antibody library for Sj was constructed. To obtain a single-chain
      variable fragment antibody (scFv) against Sj, the library was screened with
      metabolic antigens from adult Sj worms (Sj-MAg) using enzyme-linked immunosorbent
      assay. The soluble scFvs selected were used to detect Sj antigens in the serum of
      acute and chronic schistosomiasis patients. RESULTS: Six positive clones with
      good reactivity to Sj-MAg were obtained from the phage display antibody library
      of about 1.07 x 10(6) individual clones. Only two of these six clones bound
      specifically to Sj-MAg and were chosen for further analysis. Specific soluble
      anti-Sj-MAg scFvs were produced by inducing the 2 clones with isopropyl-D
      thiogalactopyranoside. The characteristics of the scFvs were then determined. The
      results of Western blot showed that these scFvs could bind to Sj-MAg specifically
      and had a molecular weight of about 31 kD. When testing serum from
      schistosomiasis patients with one of the two specific scFvs, its sensitivity was
      found to be 60% and 37% in acute and chronic patients, respectively, with a
      specificity of 90%. When the two specific scFvs were combined, their sensitivity
      was found to be 75% and 57% in acute and chronic patients, respectively, with a
      specificity of 85%. CONCLUSIONS: The results indicate that the scFvs are
      potentially useful for the diagnosis of schistosomiasis. The library construction
      also provides a useful tool for the further screening of other antibodies for
      both diagnostic and immunotherapeutic applications and for epitope analysis and
      vaccine design.

PMID- 15569490
TI  - Iron chelator daphnetin against Pneumocystis carinii in vitro.
AB  - BACKGROUND: Although there are several drugs and drug combinations for the
      treatment of Pneumocystis carinii (P. carinii) pneumonia, all drugs have the
      toxicity as well as low efficacy. Iron chelators have been proposed as a source
      of new drugs for combating these infections. We hypothesized that iron chelators
      would suppress the growth of P. carinii by deprivation of the nutritional iron
      required for growth. In this study, a short-term axenic culture system of P.
      carinii was established. Daphnetin (7,8-dihydroxycoumarin), a known iron
      chelator, was demonstrated to exhibit in vitro activity against P. carinii in
      this system. METHODS: P. carinii organisms were obtained from the lungs of
      immunosuppressed rats. The culture system consisted of Iscove Dulbecco Eagle's
      Minimum Essential Medium (IMDM), supplemented with S-adenosyl-L-methionine, N
      acetylglucosamine, putrescine, L-cysteine, L-glutamine, 2-mercaptoethanol, and
      fetal bovine serum, and was maintained at 37 degrees C, in 5% CO(2), 95% O(2), at
      the optimal pH of 8.0. The culture system was used to assess the effect of
      daphnetin on the proliferation of P. carinii organisms. The ultrastructures of
      the treated organisms were observed by transmission electron microscopy. RESULTS:
      The number of cysts and trophozoites increased 8- to 9-fold and 11- to 12-fold,
      respectively, after 10 days of culture. Daphnetin was found to suppress the
      growth of P. carinii in a dose-dependent manner at concentrations between 1
      micromol/L and 20 micromol/L. The inhibitory activity was suppressed by the
      chelation of daphnetin with ferrous sulfate in a 2:1 molar ratio, but it was not
      suppressed by mixing the culture medium with magnesium sulfate. Reduction of P.
      carinii numbers after treatment with daphnetin correlated with morphological
      changes in the organisms, as determined by transmission electron microscopy.
      CONCLUSIONS: Daphnetin can suppress the growth of P. carinii in vitro. The
      efficacy of daphnetin in suppressing the the growth of P. carinii in vitro is
      related to its ability to chelate iron.

PMID- 15569491
TI  - Toll-like receptors: function and roles in asthma.

PMID- 15569492
TI  - Clinical significance of N-terminal pro-brain natriuretic peptide.

PMID- 15569493
TI  - Anti-SARS virus antibody responses against human SARS-associated coronavirus and
      animal SARS-associated coronavirus-like virus.

PMID- 15569494
TI  - Questionnaire survey of chronic cough in asthmatic patients.

PMID- 15569495
TI  - Drug-resistance mechanisms and prevalence of Enterobacter cloacae resistant to
      multi-antibiotics.

PMID- 15569496
TI  - Impact of catheter on uroflow rate in pressure-flow study.

PMID- 15569497
TI  - Setting-up and preliminary performance of the interactive teleradiological
      conference system based on virtual private network.

PMID- 15569498
TI  - Do neutrophils actively participate in airway inflammation and remodeling in
      asthma?

PMID- 15569499
TI  - Primary choriocarcinoma in the anterior mediastinum in a man: a case report and
      review of the literatures.

PMID- 15569500
TI  - Pulmonary alveolar proteinosis treated with whole-lung lavage utilizing
      extracorporeal membrane oxygenation: a case report and review of literatures.

PMID- 15569501
TI  - Aortopulmonary window: a case diagnosed and surgery confirmed by ultra-fast
      computed tomography.

PMID- 15569502
TI  - Intravascular papillary endothelial hyperplasia of the mandibular lingual mucosa.

PMID- 15569503
TI  - Enlarged tongue due to primary systemic amyloidosis: clinicopathologic
      observation.

PMID- 15569504
TI  - [Dental instrument sterilization and control of nosocomial infection].

PMID- 15569505
TI  - [Current status of disinfection and sterilization for dental handpieces in the
      hospitals].
AB  - OBJECTIVE: To understand current status of the uses of dental handpieces, methods
      of disinfection and sterilization and their effectiveness in dental-care
      hospitals and out-patient departments of stomatology in general hospitals.
      METHODS: Ten dental-care hospitals and departments of stomatology in general
      hospitals at varied levels were randomly sampled during 2000 to 2001 to
      investigate the uses of dental handpieces and means of their disinfection and
      sterilization. One used dental handpiece from each hospital or department of
      stomatology in general hospital selected was detected for possible contamination
      of bacteria by aerobic bacterial count and Coliform bacterial examinations and
      hepatitis B surface antigen (HBsAg) on it, based on "The Technical Standards for
      Disinfection" set by the Ministry of Health of China, and the effectiveness of
      its disinfection and sterilization was evaluated as well. RESULTS: Anti-suction
      handpieces were used only in 5.9% of the hospitals or departments, 94.1% of them
      without anti-suction devices. Cleansing disinfection was applied for used dental
      handpieces in 62.9% of the dental-care hospitals and the departments of
      stomatology, with an effective rate of 26.17%, immersing disinfection in 10.0%,
      with an effective rate of 55.88%, and autoclave in 27.1%, with an effective rate
      of 80.43%. Used dental handpieces in the hospitals and departments of stomatology
      in general hospitals were all contaminated by bacteria and HBsAg could be
      detected in 1.67% of them. CONCLUSIONS: Dental handpieces without anti-suction
      should be replaced soon by those with it or comprehensive dental unit with anti
      suction device should be used. Used dental handpieces must be sterilized
      effectively before next use. Awareness on prevention from cross-infection should
      be improved for dental-care professional staff and operation of sterilization
      should be standardized.

PMID- 15569506
TI  - [In vitro selection of specific aptamers against microcystin-LR].
AB  - OBJECTIVE: In vitro selection of specific RNA aptamers against microcystin-LR
      from a random RNA pool. METHODS: A RNA library with 40 randomized nucleotide
      positions was applied to select for specific aptamers to microcystin-LR
      covalently linked to Sepharose by using a standard in vitro selection protocol.
      RESULTS: The specific enriched RNA aptamer for microcystin-LR increased step by
      step from initial round to 11th round after which a plateau of the aptamer
      quantity was observed between 11th and 13th round. The enriched RNAs from last
      round were reverse transcribed, PCR amplified and cloned into E. coli DH10 b
      competent cells. Sixty colonies were sequenced from which 38 sequences were
      aligned and classified into 3 families and 5 duplicates and no conserved
      sequences were found among them. Eight representative clones from the groups were
      selected for further binding experiments comparing with original pool RNA. Four
      clone RNAs were identified with relatively high affinity to microcystin-LR, of
      which MC25 clone RNA could combine with microcystin-LR as lower as 0.5
      micromol/L. CONCLUSION: Subpopulations of RNA molecules that bind specifically to
      microcystin-LR have been isolated from a population of random sequence RNA
      molecules, which might provide a new way for future application in environmental
      monitoring of microcystin.

PMID- 15569507
TI  - [Calculation of the combined renal dysfunction risk in patients co-exposed to
      arsenicum and cadmium by using benchmark dose method].
AB  - OBJECTIVE: To research the impairment of renal function and the combined effects
      of arsenic and cadmium exposure in population residing in polluted area, and to
      calculate the benchmark doses of urinary arsenic (UAs) and cadmium (UCd) in renal
      dysfunction. METHODS: The concentrations of Uas and UCd were used as as exposure
      biomarker. Urinary beta(2)-microglobulin (Ubeta(2)-MG), N-acetyl-beta
      glucosaminidase (UNAG), and albumin were calculated as biomarkers of renal
      dysfunction. The benchmark dose (BMD) and the lower confidence limit of the
      benchmark dose (BMDL) were calculated. Totally 245 patients were enrolled in the
      study, them, of 122 were from the exposed area, and 123 from the control area.
      RESULTS: UAs and UCd concentrations in the exposed group were shown significantly
      higher than those in the control group (P < 0.01). The levels of Ubeta(2)-MG,
      UNAG and urinary albumin in the exposed group were significantly higher than
      those of the controls (P < 0.01). There existed positive correlation among the
      concentrations of UAs, UCd, Ubeta(2)-MG, urinary albumin and UNAG, showing a
      significant dose-effect relationship. The combination of cadmium and arsenic
      caused even more renal injury than by chemicals alone in a same dose. The
      BMD/BMDL of UAs were estimated as 121.91-171.88 microg/g Cr and 102.11-144.44
      microg/g Cr. Of UCd, the BMD/BMDL were 1.05-1.48 microg/g Cr and 0.88-1.24
      microg/g Cr. CONCLUSIONS: This study indicates the combination of cadmium and
      arsenic might cause even more renal injury than by chemicals given alone, and
      cadmium might cause potential arsenic nephrotoxicity during long-term coexposure
      to arsenic and cadmium in human beings. It also suggests that UAs and UCd should
      be kept below 102.11 and 0.88 microg/g creatinine as to preventing renal damage
      from coexposure to arsenic and cadmium. The BMD method should be used in
      calculating the BMD of UAs and UCd on renal dysfunction.

PMID- 15569508
TI  - [Impact of low-level lead exposure on neural cell adhesion molecule expression of
      primarily cultured hippocampal neurons].
AB  - OBJECTIVE: To study the impact of low-level lead exposure on neural cell adhesion
      molecule (NCAM) expression of primarily cultured hippocampal neurons. METHODS:
      Wistar rats gestated at 18th day were anaesthetized and paunched to get the pups,
      the hippocampi of the pups were separated and the hippocampal neurons were
      primarily cultured. After co-cultivated with different dosage of PbCl(2), the
      NCAM expression of the neurons were tested with Western blotting at different
      culture time. RESULTS: Normally, the expression of NCAM at the 1st culture day
      was very low and its integral obsorbency density was 14; the climax expression
      time of NCAM of the cultured hippocampal neurons was 3rd to 5th cultured day, and
      their integral obsorbency density were 2 542 to 2 580; henceforth, the NCAM
      expression declined. NCAM expression was inhibited significantly by lead during
      the 2nd to 4th cultured day, and dose-response relationship was observed. The
      inhibition of lead weakened along with the cultured time prolonged, at 5th
      cultured day, it disappeared, and the NCAM expression of 10(-2), 10(-3) and 10(
      4) mmol/L groups even exceeded the control groups. After that, the expression of
      NCAM in all groups began to decline, and the dose-response relationship of lead
      to the NCAM expression was observed again. CONCLUSION: Low-level lead might
      significantly inhibit the NCAM expression of the primarily cultured Wistar rats'
      hippocampal neurons, and might delay the climax NCAM expression time.

PMID- 15569509
TI  - [Experimental studies on male reproductive toxicity of bisphenol A in vitro and
      vivo].
AB  - OBJECTIVE: To explore the effects of Bisphenol A in adult rats and its possible
      mechanisms. METHODS: BPA (in corn oil) was administered orally to 9-week-old male
      Sprague-Dawley rats for 14 days (0, 1 and 5 g/kg bw), and incubated primary
      Sertoli cells from pubertal SD rats with 0, 10(-7), 10(-6), 10(-5), 10(-4) mol/L
      BPA. RESULTS: After oral administration, a significant decrease in right testis
      weight was observed in 5 g/kg dose group, but not in the 1 g/kg bw dose group.
      Germ cells were detached from basement membrane of seminiferous tubules and
      Sertoli cells in BPA-treated groups. Administration of BPA at 1 g/kg bw and 5
      g/kg bw produced both nucleus pycnosis and vacuolized nucleus in germ cells and
      Sertoli cells. A marked loss in vimentin staining in Sertoli cells from testis of
      BPA-treated rats was detected. No change in levels of serum estradiol and
      testosterone was observed after two-week exposure to BPA. In Sertoli cell primary
      culture, BPA destroyed the cytoskeleton and cell-cell junctions, and elongated
      Sertoli cells. CONCLUSION: These results suggest that BPA may injure reproductive
      function of male rats by destroying the cytoskeleton and changing the form of
      Sertoli cells.

PMID- 15569510
TI  - [Reversibility of adverse effects of di-n-butyl phthalate on F1 generation rat
      testes].
AB  - OBJECTIVE: To study the reversibility of di-n-butyl phthalate (DBP) effects on
      F(1) generation rat testes. METHODS: Pregnant rats were treated with different
      dose of DBP (0, 50, 250 and 500 mg per kg per day) by gavage from GD1 to PND21.
      The adverse effects of DBP on testes of F(1) male rats in different developmental
      period (PND14, 21 and 70) were observed by anatomy and pathological methods.
      RESULTS: There was no difference in rat testis weight and testis/body weight
      between DBP-treated group and the control. From the results of pathology and
      sertoli cell counting, comparing with the control, thinner seminiferous
      epithelium, decreased cell number and vacuole cells were observed in PND14 male
      DBP-treated rats. In PND21 rats, the number and form of sertoli cells were
      recovered and few exfoliated spermatogenic cells were found. When maturing to
      PND70, few rats were found irreversible damages such as seminiferous tubule
      degeneration, seminiferous epithelium atrophy, etc. CONCLUSION: These results
      suggest that adverse effects of DBP on young rat testes should be reversibility.

PMID- 15569511
TI  - [Preliminary study on naphthalene-metabolites-albumin adduct as an exposure
      biomarker for coke oven workers].
AB  - OBJECTIVE: To study albumin adduct with naphthalene metabolites, namely 1,2
      naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ), as a potential
      biomarker for intermediate/long-term exposure to polycyclic aromatic hydrocarbons
      (PAH) in coke oven workers. METHODS: Twenty-eight coke oven workers and 22
      control workers were recruited from a cokery. Spot urine and venous blood samples
      were collected from the workers after four continuously working days and personal
      information was obtained by questionnaire. Plasma albumin adduct was detected
      with gas chromatography-mass spectrometry. RESULTS: Albumin adduct with 1,2- &
      1,4-NPQ (1,2-NPQ and 1,4-NPQ), respectively, were detected in all coke oven
      workers and controls. Median plasma level of 1,2-NPQ-Alb in coke oven workers was
      significantly higher than that in controls (76.6 pmol/g vs. 44.9 pmol/g, P <
      0.01). However, there was no significant difference in plasma median level of 1,4
      NPQ-Alb between the two groups (48.6 pmol/g vs. 44.2 pmol/g, P > 0.05). Plasma
      level of 1,2-NPQ-Alb was significantly higher than that of 1,4-NPQ-Alb in coke
      oven workers. Urine levels of naphthalene, 1-naphthol, 2-naphthol and 1-pyrenol
      in coke oven workers correlated significantly with their plasma level of 1,2-NPQ
      Alb (Pearson coefficient of correlation greater than 0.371, P < 0.01), but did
      not do significantly with 1,4-NPQ-Alb. CONCLUSION: Plasma level of 1,2-NPQ-Alb
      could effectively reflect their magnitude of personal internal dose of exposure
      to air PAH, so it could be used as a potential biomarker to evaluate their
      intermediate/long-term exposure to PAH in coke oven workers.

PMID- 15569512
TI  - [Role of cyclin D1 in carcinogenesis of human cells induced by quartz].
AB  - OBJECTIVE: To study the role of cyclin D1 in malignant transformation of human
      embryonic lung diploid fibroblasts (HELF) induced by quartz. METHODS: pXJ41
      cyclin D1 expressing sense and antisense cyclin D1 RNA were transinfected into
      malignant transformed HELF induced by quartz with DNA recombination and gene
      transduction. The expression of cyclin D1 was detected with hybridization in situ
      and immunohistochemistry methods to analyze changes in cell growth, double
      multiplication time, distribution of cell cycles, colony forming ability on soft
      agar, etc., before and after cyclin D1 transduction. RESULTS: During the process
      of malignant transformation of HELF induced by quartz, cyclin D1 gene was
      overexpressed. Antisense pXJ41-cyclin D1 RNA could suppress the growth and
      proliferation of malignant transformed cells induced by quartz. Growth speed of
      antisense pXJ41-cyclin D1 transinfected cells decreased by 58.69% on the 8th day
      in culture, as compared to malignant transformed cells induced by quartz, and its
      double multiplication time prolonged from 21.0 h to 31.4 h. Antisense cyclin D1
      RNA led to cell cycle arrest, resulting in lengthened G1 phase (proportion of
      cells in phase G1 increased to 52.7% from 45.1% and that of cells in phase S
      decreased to 33.1% from 40.3%). Colony forming rate reduced significantly and
      size of colony became smaller. CONCLUSIONS: Abnormal expression of cyclin D1 in
      cells related to their malignant transformation induced by quartz. Highly
      expressed cyclin D1 could play an important role in maintaining the transformed
      phenotype of malignant cells.

PMID- 15569513
TI  - [Effects of folic acid cooperated with soybean isoflavone on the neural tube
      defects pregnant rats].
AB  - OBJECTIVE: To study the effect of folic acid cooperating with soybean isoflavone
      on the oxidative status of neural tube defects (NTDs) pregnant rats induced by
      cyclophosphamide, to observe the relationship of the two factors, folic acid and
      the isoflavone and to look for the best co-intervention group. METHODS: The 100
      pregnant rats of 2.5-3 months old were randomly divided into the control group,
      model group, co-intervention groups and solo-intervention groups. The animals
      were executed on the 20th day of gestation as to examining the levels of
      antioxidative indices (GSH, GSH-Px, Se, Mn, Fe) in blood. The incidence rates of
      NTDs were calculated. RESULTS: The interaction of folic acid and isoflavone had
      significant effect on the indices related with antioxidation (P < 0.05). Folic
      acid 0.7 mg/kg cooperated with isoflavone 160 mg/kg had the best intervention
      effects in our study. Compared with the solo-intervention by folic acid 1.4 mg/kg
      and isoflavone 320 mg/kg, the effect of co-intervention (folic acid 0.7 mg/kg
      cooperated with isoflavone 160 mg/kg) was significantly better (P < 0.05).
      CONCLUSION: Folic acid should be the main protective factor of NTDs, and
      isoflavone might reinforce the protective effects of folic the acid on NTDs by
      increasing the antioxidative ability, however, the effect is related with the
      ratio of the two factors.

PMID- 15569514
TI  - [Copper treatment alters the barrier functions of human intestinal Caco-2 cells].
AB  - OBJECTIVE: To investigate the effects of copper on permeability and P
      glycoprotein (P-gp) of Caco-2 cell monolayers. METHODS: The differentiated Caco-2
      cell model was used in this study. Permeability of cell monolayers was reflected
      by monitoring transepithelial electrical resistance (TEER); distribution of tight
      junctional protein ZO-1 was measured by immunofluorescent staining; F actin was
      measured by fluorescence staining; and Activity of P-gp was reflected by changes
      of transcellular transport and accumulation of Rho-123 in Caco-2 cells. RESULTS:
      Apical treatment with copper (30 - 100 micromol/L, Hanks' buffered salt solution,
      up to 3 hours) induced a time- and concentration-dependent increase in
      permeability reflected by progressive decrease of TEER of Caco-2 cell monolayers,
      accompanied by deorganization of F actin, but without significant effects on
      tight junctional protein ZO-1; at a dose without any adverse effects on viability
      and permeability of Caco-2 monolayers, copper treatment (300 micromol/L, complete
      medium, 24 hours) decreased Papp(BL-->AP) from 7.37 +/- 0.20 x 10(-6) cm/s
      (controls) to (6.43 +/- 0.27) x 10(-6) cm/s, the increased Papp(AP-->BL) from
      (1.23 +/- 0.05) x 10(-7) cm/s (controls) to (3.41 +/- 0.08) x 10(-7) cm/s, and
      enhanced the intracellular Rho-123 from (0.31 +/- 0.01) nmol/filter (controls) to
      (0.50 +/- 0.03) nmol/filter. CONCLUSION: Copper might alter the barrier functions
      of Caco-2 cells through increasing the permeability and inhibiting P-gp of Caco-2
      cells.

PMID- 15569515
TI  - [Study on the transcriptional modulation of cytochrome P450 3A4 expression by
      zearalenone].
AB  - OBJECTIVE: To study whether zearalenone (ZEA), a fungal estrogen, can
      transcriptionally up-regulate the expression of cytochrome 450 3A4 (CYP3A4)
      transcription by activating human steroid hormone and xenobiotic receptor (SXR).
      METHOD: Transient cotransfection reporter gene assays were performed with human
      SXR expression plasmid and a reporter plasmid containing the SXR in the CYP3A4
      gene promoter in HepG(2) cells. RESULTS: The transcriptional induction of CYP3A4
      by ZEA with a dose, time-dependent manner. ZEA at the concentrations of 0.01,
      0.10, 1.00 and 10.00 micromol/L, respectively, could induce CYP3A4 with (1.50 +/-
      0.21), (1.66 +/- 0.27), (3.04 +/- 0.82) and (3.96 +/- 1.16) folds, as compared
      with 0.1% DMSO. Results from a time-dependent study show that 1.00 and 10.00
      micromol/L of ZEA for 12 to 48 hours could enhance the transcription of CYP3A4
      with (3.69 +/- 1.34) and (5.18 +/- 1.50) folds, and 10.00 micromol/L of ZEA for
      48 hours could induce the CYP3A4 gene expression (5.18 +/- 1.50) folds, as
      compared with 0.1% DMSO by activating human SXR. CONCLUSION: ZEA could induce the
      expression of the CYP3A4 gene transcription through activating SXR, possibly by
      affecting the other substrates of the CYP3A4, especially affecting the metabolism
      of drugs in the body.

PMID- 15569516
TI  - [Effects of vitamin D analogue EB1089 on proliferation and apoptosis of hepatic
      carcinoma cells].
AB  - OBJECTIVE: This study aimed at investigating the effects of vitamin D analogue
      EB1089 on the proliferation and apoptosis of hepatic carcinoma cells. METHODS:
      Hepatic carcinoma cell strain G(2) (Hep-G(2)) in which prominent vitamin D
      receptor (VDR) mRNA could be expressed and the cell strain T (HCC-T) negative in
      VDR gene expression were incubated in culture media with 100 nmol/L, 10 nmol/L
      and 1 nmol/L EB1089 for 2 d, 4 d and 6 d, respectively. Survival and
      proliferation of the cells were detected by blue tetrazolium colorimetric test
      and plate clone-forming test, the VDR mRNA expression was determined by reverse
      transcription-polymerase chain reaction (RT-PCR) and apoptosis of the cells was
      detected by flow cytometry (FCM) and electron microscopy. RESULTS: EB1089 could
      inhibit the proliferation of hepatocellular cell line Hep-G(2) that expressed
      prominent vitamin D receptor mRNA, the inhibitory rate is 17.5% approximately
      72.1%. On the other hand, EB1089 had no anti-proliferative effect on
      hepatocellular cell line HCC-T in which the gene expression of vitamin D
      receptors was negative. The electron microscope results showed that EB1089 could
      induce apoptosis of hepatocarcinoma cells and the percentages of apoptotic cells
      measured by flow cytometer was 21.4%. Cell cycle progression was blocked at G(1)
      phase with EB1089. CONCLUSION: EB1089 could inhibit proliferation of human Hep
      G(2), probably through VDR, and induce apoptosis of the cells.

PMID- 15569517
TI  - [Relationship between acute dipterex poisoning and oxidative stress and free
      radical damage].
AB  - OBJECTIVE: To study relationship between acute dipterex poisoning and oxidative
      stress and free radical damage. METHODS: Eighty-two patients with acute dipterex
      poisoning (ADPP) and ninety-two healthy adult volunteers (HAV) were enrolled in
      the study with randomized controlled trial design. Plasma levels of vitamin C
      (VC) and vitamin E (VE), as well as level of lipoperoxide (LPO) and activities of
      superoxide dismutase (SOD) and acetylcholinesterase (AChE) in the red blood cells
      (RBC), were determined by spectrophotometry. RESULTS: Levels of VC and VE, and
      activities of SOD and AChE were (37.35 +/- 9.98) micromol/L, (16.57 +/- 4.54)
      micromol/L, (1 785 +/- 154) U/g Hb and (213.1 +/- 57.6) U/g Hb, respectively, in
      the ADPP group, significantly lower than those in the HAV group, (55.34 +/-
      15.98) micromol/L, (25.66 +/- 7.24) micromol/L, (2 124 +/- 185) U/g Hb and (305.3
      +/- 83.6) U/g Hb, respectively. Plasma level of LPO was (35.20 +/- 5.29) nmol/g
      Hb in the ADPP group, significantly higher than that in the HAV group, (27.87 +/-
      4.66) nmol/g Hb. Partial correlation analysis suggested that there existed
      negative correlation between activity of AChE in the RBC and plasma level of LPO
      (r = -0.274, P = 0.013) and positive correlation between activity of AChE in the
      RBC and plasma levels of VC and VE, and activity of SOD in the RBC (r = 0.333, P
      = 0.002, r = 0.269, P = 0.015 and r = 0.248, P = 0.026, respectively) in the
      ADPP, adjusted for age. Coefficient of reliability alpha was 0.682 (P < 0.001),
      with a standardized alpha of 0.868 (P < 0.001). CONCLUSION: There exist severe
      oxidative stress and free radical damage in patients with acute dipterex
      poisoning.

PMID- 15569518
TI  - [Flow injection hydrogen compound production atom absorption spectrometry in the
      determination of blood selenium].

PMID- 15569519
TI  - [A method to manage of miss data--multiple imputation].

PMID- 15569520
TI  - [Personal protection of the rescuers in sudden accident of public health events].

PMID- 15569526
TI  - [Preparation of rAAV2/hFIX and experimentally application to gene therapy for
      hemophilia B].
AB  - OBJECTIVE: To prepare the rAAV2/hFIX and evaluate the efficiency of the
      preparation on gene therapy of hemophilia B model mice. METHODS: The rAAV-2/hFIX
      was prepared by "one helper virus-one vector cell line" strategy and transfected
      both BHK-21 and C2C12 cells in vitro. The hFIX antigen level in cell culture
      supernatant was assayed. The rAAV-2/hFIX was injected into muscles of hemophilia
      B model mice and assayed the serum hFIX levels, hFIX clotting activity, bleeding
      time, 5 min bleeding volume. RESULTS: The hFIX antigen could be detected from 24
      h till 120 h after BHK-21 and C2C12 cells were transfected with highest levels at
      24 h reaching (51.0 +/- 6.5) ng/10(5) cells and (68.0 +/- 7.2) ng/10(5) cells,
      respectively. The rAAV2/hFIX injected mice could efficiently express hFIX and
      peaked at three weeks after injection, then slowly decreased but low level hFIX
      antigen was still detectable till 10 weeks after injection. There were
      significant differences between the high, middle and low dose groups of
      rAAV2/hFIX and the control group (P < 0.01), the plasma FIX clotting activities
      in the model mice were improved remarkably, bleeding time was greatly shortened
      and bleeding in 5 min was decreased. The hFIX expression level and FIX clotting
      activity of the high dose of rAAV2/hFIX group (1.6 x 10(13) v.g./kg) reached
      about (387.0 +/- 12.5) ng/ml plasma in contrast with the normal levels of (30.0
      +/- 5.5)% at the third week after injection. No rAAV2 vector DNA was detected in
      the organs except for injected muscle tissue. CONCLUSION: The rAAV2/hFIX
      transfected BHK-21 and C2C12 cells could efficiently express hFIX antigen and was
      of therapeutic effects for the hemophilia B model mice by intramuscularly
      injection.The results provide the basis for clinical trial of rAAV2 gene therapy
      for hemophilia B.

PMID- 15569527
TI  - [Inherited coagulation factor X deficiency caused by two novel mutations in
      factor X gene].
AB  - OBJECTIVE: To explore the molecular mechanisms involved in a pedigree with
      inherited coagulation factor X (FX) deficiency. METHODS: The activated partial
      thromboplastin time (APTT), prothrombin time (PT), FX activity (FX:C) and FX
      antigen (FX:Ag) test were adopted for phenotype diagnosis. All the 8 exons,
      intron/exon boundaries and the 5'untranslated regions (UTR) of the FX gene were
      amplified by polymerase chain reaction (PCR) from the genomic DNA extracted from
      the peripheral blood of the propositus. The PCR products were screened by direct
      sequencing. The mutation was confirmed by allele specific PCR (ASPCR). RESULTS:
      The phenotype of the propositus was identified as FX deficiency (type II). Two
      novel FX gene mutations were detected in the propositus: one was a donor site
      splice mutation in intron 1 (IVS1 + 1G-->A), another was a missense mutation
      1185G-->A in exon 8 (Arg347His). CONCLUSION: The FX deficiency of the propositus
      is caused by double heterozygous mutations IVS1 + 1G-->A and Arg347His.

PMID- 15569528
TI  - [The effects of tissue factor/activated factor VII complex on the invasion and
      metastasis of human ovarian cancer].
AB  - OBJECTIVE: To explore the role of tissue factor/activated factor VII (TF/FVIIa)
      complex in human ovarian cancer invasion and metastasis. METHODS: (1) Constructed
      an expression vector of TF, pcDNA3-TF and established a human ovarian cell line
      A2780/TF expressing high level TF by using molecular cloning and gene
      transfection techniques. (2) By Boyden chamber assay to count the numbers of
      A2780 and A2780/TF cells that penetrated the matrigel to the back of PVPF
      membrane after FVIIa stimulation. (3) BALB/c nude mice were used to establish
      experimental model of metastasis with A2780 or A2780/TF and the lung tissue
      sections were examined by microscopy for cancer metastasis. RESULTS: (1) Compared
      with their parental A2780 cells, A2780/TF cells expressed high level of TF mRNA
      (3.99 +/- 0.15 vs 0.97 +/- 0.23, P < 0.01) and TF antigen on cell surface
      ?[(48.56 +/- 9.53)% vs (2.73 +/- 1.15)%, P < 0.01?]. (2) After stimulation, the
      A2780/TF cell number on the back of PVPF membrane increased from basal level
      157.3 +/- 19.2 to 447.7 +/- 39.4 (P < 0.01), which could decreased to basal level
      when coincubated with anti-TF antibody. (3) Cancer metastasis was found in 22.2%
      of nude mice transplanted with A2780 cells, while in 88.9% of those transplanted
      with A2780/TF cells. CONCLUSION: TF could promote the invasion and metastasis of
      human ovarian cancer cells through TF/FVIIa pathway.

PMID- 15569529
TI  - [Report of 8 cases of bcr-abl gene positive thrombocytosis and review of the
      literature].
AB  - OBJECTIVE: To analyse the features of 8 cases of Bcr(+) thrombocytosis. METHODS:
      The clinical and hematological features and therapeutic outcomes were studied
      retrospectively in 8 Bcr(+) thrombocytosis and compared with essential
      thrombocytosis (ET) and chronic myeloid leukemia-chronic phase thrombocytosis
      (CML-CP-T). BCR-ABL fusion gene was detected with PCR. RESULTS: (1) Except for
      the presence of BCR-ABL fusion gene, there was no significant difference in
      clinical and hematological features and therapeutic outcomes between
      thrombocytosis with or without BCR-ABL. (2) The Bcr(+) thrombocytosis differed
      from CML-CP-T in the following aspects: female predominance, milder or no
      splenomegaly, peripheral leukocytes count < 40 x 10(9)/L, less or no basophilia
      and fewer immature granulocytes in peripheral blood, bone marrow granulocytic
      and/or megakaryocytic lineage hyperplasia, normal or increased neutrophil
      alkaline phosphatase score and less blastic transformation. CONCLUSION: Bcr(+)
      thrombocytosis may be considered as a new member of chronic myeloproliferative
      diseases, a variant of essential thrombocythemia.

PMID- 15569531
TI  - [Effects of vascular endothelial growth factor on differentiation and function of
      dendritic cells generated from CD34+ hematopoietic progenitor cells in vitro].
AB  - OBJECTIVE: To investigate the effects of vascular endothelial growth factor
      (VEGF) on differentiation and function of dendritic cells derived from CD34+
      hematopoietic progenitor cells. METHODS: After isolation from umbilical cord
      blood with a high-gradient magnetic cell sorting system (MACS), the CD34+ cells
      were cultured with a cocktail cytokines for differentiating into dendritic cells
      (DC). The cells were stimulated by VEGF (25 ng/ml) either at the beginning or at
      day 9 of culture. Kinetics analysis of cell proliferation was performed during
      the process of cell culture, and the expression of DC differentiation antigens
      including CD1alpha, CD83, CD80, CD54 and HLA-DR was examined by flow cytometry.
      DC function was evaluated by the ability to induce proliferation of allogeneic T
      cells in mixed lymphocyte reaction (MLR) assay, and the production of IL-12 by
      ELISA. RESULTS: VEGF added at day 1 of culture induced an increase of total cell
      numbers by (1.51 +/- 0.23)-folds (P = 0.001). VEGF added at the initial but not
      the late stage of culture could dramatically down-regulate the expression of CD1a
      [(33.00 +/- 2.12)% vs (81.20 +/- 6.93)%], CD83 [(42.23 +/- 1.15)% vs (87.98 +/-
      7.97)%], CD80 (42.93 +/- 1.32)% vs (94.53 +/- 0.87)%], and HLA-DR [(37.93 +/-
      5.30)% vs (74.15 +/- 3.74)%], while obviously up-regulate the expression of CD14.
      Moreover, the inhibitory effect of VEGF on DC function was confirmed by a reduced
      ability to induce proliferation of allogeneic T cells and production of IL-12 (P
      < 0.01). CONCLUSIONS: VEGF could induce the expansion of hematopoietic progenitor
      cells and inhibit at the early stage their differentiation into mature DC.

PMID- 15569532
TI  - [Hereditary hemorrhagic telangiectasia resulted from a nonsense mutation Arg479
      Stop in the ALK-1 gene].
AB  - OBJECTIVE: To identify the gene mutations in a pedigree with hereditary
      hemorrhagic telangiectasia. METHODS: Genomic DNA was extracted from the
      peripheral blood of the propositus. All of the exons, intron/exon boundaries and
      the 5' untranslation regions (UTR) of the ALK-1 and endoglin gene were amplified
      by polymerase chain reaction (PCR). The PCR products were screened by direct
      sequencing. RESULTS: The mutation is a C1437T substitution in exon 10 of the ALK
      1 gene, resulting in Arg 479 Stop. CONCLUSION: The hereditary hemorrhagic
      telangiectasia propositus is caused by a heterozygous Arg 479 Stop mutation in
      the ALK-1 gene which has not been identified previously.

PMID- 15569533
TI  - [A study of human annexin V derivative: its effects of anticoagulation and
      antithrombosis].
AB  - OBJECTIVE: To investigate the effects of a new anticoagulant, annexin V
      derivative (AND) on anticoagulation and antithrombosis. METHODS: High and low
      doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous
      (iv) bolus injections followed by half the respective AND doses by iv infusion
      over 2 hours. Control groups were iv given heparin (group 3) and saline (group 4)
      of the same volume and procedure as that in group 1 and 2. Blood cell count,
      activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin
      time (TT) and fibrinogen level were examined before and 15, 30 and 60 min after
      iv bolus and 2 hours after the end of iv infusion. A 3.0 mm x 15 mm balloon was
      put into femoral artery to induce endothelial denudation 15 min after IV bolus
      and the blood pressure of femoral artery was monitored until the pulse pressure
      recorded 0 mm Hg when the vessel was occluded completely by a thrombus. The
      femoral arteries were collected and the thrombi were stripped off for measuring
      their lengths, wet and dry weights. RESULTS: Anticoagulation parameters: APTT at
      15 min after iv bolus in AND group was significantly longer than that in group 4
      (P < 0.05) but shorter than that in group 3 (P < 0.05); APTT and TT in group 3
      were significantly longer than those in groups 1, 2 and 4. Fibrinogen: 0.70 mg/kg
      AND may decrease fibrinogen. Antithrombosis values: the wet and dry weights in
      AND groups were significantly lighter than those in group 3 and 4 (P < 0.05). The
      dry weight in high-dose AND group was remarkably lighter than that in low-dose
      group (P = 0.029). The length of thrombus in low-dose AND group was remarkably
      shorter than that in group 4 (P = 0.013), but not for group 3 (P > 0.05). It was
      remarkably shorter in high-dose AND group than in both group 3 (P < 0.001) and 4
      (P = 0.015). The time when pulse pressure equaled to 0 was longer in AND group
      than in group 4 (P < 0.05), but not in 3. CONCLUSION: AND is an effective
      anticoagulant and antithrombosis agent, the highest anticoagulation effect occurs
      at 15 min after IV bolus. Its anticoagulation effect is not more potent than that
      of standard heparin, while antithrombosis capacity is more effective. AND in
      treating thrombosis clinically might be promising.

PMID- 15569534
TI  - [Effects of 2A-1-1 on the aggregation and Ca2+ influx of platelets].
AB  - OBJECTIVE: To explore the effects of 2A-1-1 (purified component from Panax
      notoginsengs saponins) on the aggregation of and Ca2+ influx into human
      platelets. METHODS: The aggregation of platelets was tested by nephelometry, Fura
      2 fluorescent technique was used for detecting cell [Ca2+]i. The effects of 2A-1
      1, nifedipine and SK&F96365 on Ca(2+) influx into human platelets induced by ADP
      or CPA were observed separately. RESULTS: Nifedipine (< 20 micromol/L) could not
      inhibit platelet aggregation induced by ADP or the Ca(2+) influx induced by ADP
      or CPA. SK&F96365 at 20 micromol/L could inhibit the maximal aggregation of
      platelets induced by ADP with a inhibitory rate of 59.83%, at 15 micromol/L could
      inhibit the Ca2+ influx induced by CPA or ADP. 2A-1-1 (5, 10 and 20 micromol/L)
      could inhibit the maximal aggregation of platelets induced by ADP with the
      inhibitory rates of 47.06%, 53.47% and 71.52%, respectively. 2A-1-1 at 10 and 20
      micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. CONCLUSIONS: 2A-1
      1 can inhibit platelets aggregation, block the ROC (Receptor-dependent Ca2+
      channels) and inhibit Ca2+ influx of human platelets.

PMID- 15569536
TI  - [Clinical and molecular-biological study of a May-Hegglin anomaly family].
AB  - OBJECTIVE: To study the changes of platelet in May-Hegglin anomaly (MHA) and the
      molecular pathogenesis mechanism. METHODS: Peripheral blood was drawn from the
      MHA proband, her father and her uncle. Platelet count and morphology were
      examined by automatic blood cell counter and microscopy, respectively. The
      platelet membrane protein was examined by flow cytometry. Membrane antibodies
      were determined by ELISA. PCR was used to amplify the exons 25, 31 approximately
      32, 38 and 40 of the MYH 9 gene in the MHA patient and her diseased father.
      Furthermore, PCR products were sequenced, a specific point mutation was
      identified and inclusions (Dohle's body) in the neutrophil was detected by
      indirect immunofluorescence technique. RESULTS: It was proved that in MHA
      patients, platelet count was higher by cell counter than by microscope (P <
      0.01). Giant platelet was 94% but platelet membrane proteins (CD41, CD61, CD42A,
      CD42b) were in normal range. Membrane antibodies was undetectable. An A5521G
      mutation (GAG-->AAG) in the exon 38 was found in the proband and her diseased
      father, resulting in a characteristic change of NMMHC-A1841 (Glutamic acid-
      >Arginine), which was not found in other members of the family and in normal
      controls. Spindle-like inclusions with fluorescence were clearly displayed in
      neutrophil cytoplasm. CONCLUSION: The molecular pathogenesis mechanism of May
      Hegglin anomaly is the mutation in MYH 9 gene.

PMID- 15569537
TI  - [Study on the targeting effects of M1-GS RNA on K562 cells].
AB  - OBJECTIVE: To determine the effects of M1-GS RNA (M1 RNA) on bcr-abl mRNA and
      oncoprotein after M1 RNA with guide sequence (M1-GS RNA) targeting the oncogene
      was transfected into K562 cells. METHODS: pAVGS4 (an eukaryocyte expression
      vector containing M1-GS RNA sequence) and pNAV-1 (as the control) were
      transfected into K562 cells by X-tremeGENE Q2. Total RNA was extracted at 24, 48,
      72 and 96 hours after transfection. Then RT-PCR was done to compare the products
      at different time point. After collecting pAVGS4-transfected cells and the
      control cells at 48 and 96 hours after transfection, total protein was extracted
      and quantified. Change of P210 was determined by Western blot. Colony formation
      was analyzed at 96 hours after transfection. RESULTS: RT-PCR based on transfected
      cells at different time point showed that the amount of bcr-abl mRNA began to
      decrease at 24 hours and reduced to 9.2% and 2.5% respectively at 48 and 72 hours
      after transfection. Western blot showed that the expression of P210 in the pAVGS4
      group reduced to 10.4% of the control at 48 hours and 6.7% of the control at 96
      hours after transfection. The inhibition rate of colony formation was 81.3% after
      K562 cells were transfected by pAVGS4. CONCLUSION: pAVGS4 can efficiently destroy
      bcr-abl mRNA in K562 cells. The transcript level of bcr-abl mRNA was reduced with
      the time after transfection. The expression of P210 was decreased significantly
      at 48 and 96 hours after transfection. K562 cell colony formation was prominently
      inhibited.

PMID- 15569549
TI  - Socio-economic and diagnostic aspects of tuberculosis in Pakistan.

PMID- 15569550
TI  - Diabetes and hypertension: public awareness and lifestyle - findings of a health
      mela.
AB  - OBJECTIVE: To determine the frequencies of diabetes, hypertension and their
      established lifestyle risk factors and to assess the level of awareness about
      diabetes and hypertension amongst persons attending a health mela at the Aga Khan
      University Hospital (AKUH), Karachi. DESIGN: Cross-sectional, analytical study.
      PLACE AND DURATION OF STUDY: One-day health mela held at AKUH, Karachi. SUBJECTS
      AND METHODS: A total of 264 participants were administered structured
      questionnaire to obtain demographic data and perceptions about diabetes and
      hypertension after taking verbal informed consent. Height, weight, blood pressure
      and random blood glucose were measured. RESULTS: Overall frequency of type 2
      diabetes was 13.6%, impaired glucose tolerance (IGT) 8.3% and hypertension 24%.
      Frequency of diabetes and hypertension in both men and women increased with
      increasing age(p<0.001) and body mass index (p=0.02). Over half the men and women
      with type 2 diabetes (53% and 57% respectively) and 42% men and 60% women with
      IGT also had hypertension. Diabetes and hypertension were correctly defined by
      52% and 37% subjects respectively and this was significantly associated with
      educational level (p=.001). Lack of physical exercise was observed in 59%
      participants, while 53.6% men and 67.5% women were overweight/obese. As compared
      to women, men used more additional salt (p=0.03) and had more outside meals
      (p<0.001) and snacks (p=0.01). CONCLUSION: High frequencies of diabetes,
      hypertension, obesity, unhealthy nutrition and lack of exercise were observed in
      the study population. Emphasis on health education is needed to increase public
      awareness of the warning signs and risk factors of these common conditions.

PMID- 15569551
TI  - Success rate of resin bonded restorative dentistry bridges.
AB  - OBJECTIVE: To assess the success rate of resin bonded bridges. DESIGN: A
      descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Fatima Jinnah
      Dental College Hospital, Karachi between August 1998 and August 2002. SUBJECTS
      AND METHODS: Seventy resin bonded bridges fitted in 60 patients were clinically
      assessed for debonding. The inclusion criteria included minimal reduction of
      teeth with minimal occlusal contacts. Patients were excluded if teeth had a large
      discrepancy of space and heavy occlusion. The retainers were designed self
      retentive and covered the maximum tooth surface lingually and proximally.
      Impressions were taken and resin bonded bridges were fabricated and bonded.
      Information regarding the patient's data, bonding and debonding was collected on
      a proforma and was analysed using SPSS version 10.0. RESULTS: Seventy resin
      bonded bridges had been in place for an average of 33 months. The results showed
      a 94.3% success rate. Statistically significant results were found between
      anterior bridges and posterior bridges for bonding status (p< 0.05). Results were
      not significant where maxillary versus mandibular bridges were compared for
      bonding status. (p>0.05). CONCLUSION: Resin bonded bridges achieved a high level
      of clinical success in the study.

PMID- 15569552
TI  - Frequency of hepatitis C in obstetric cases.
AB  - OBJECTIVE: To compare the frequency of antihepatitis C virus (HCV) after single
      blood transfusion, multiple blood transfusion and in non-transfused obstetric
      cases. DESIGN: A comparative descriptive study. PLACE AND DURATION OF STUDY: The
      Department of Obstetric and Gynaecology, Jinnah Postgraduate Medical Centre,
      during the period of one-year from January 2002 to December 2002. PATIENTS AND
      METHODS: Patients included in the study after single transfusion were 38, after
      multiple transfusion 39, and controls 120. History of patients regarding all the
      relevant information and clinical examination were recorded on a specially
      designed and coded proforma. Anti-HCV was detected by Roche HCV EIA 2nd
      generation kit method in all cases and controls. Descriptive statistics and
      frequency of anti HCV in each group was calculated using SPSS version 10.
      RESULTS: Frequency of anti-HCV among patients with single blood transfusion was
      13.2% (5), with multiple transfusion was 15.4% (6) and 6.6% (8) in non-transfused
      subjects. CONCLUSION: Anti-HCV frequency after one pint blood was almost same
      (13.2%) as after multiple transfusion (15.4%). This positively provided a firm
      argument for the necessity of a nationwide blood donor screening for anti-HCV by
      most sensitive immunoassay. Equally important was the need for clear cut
      indication for single blood transfusion.

PMID- 15569553
TI  - Frequency and transmission mode of hepatitis C virus in northern Sindh.
AB  - OBJECTIVE: To study the frequency of hepatitis C and mode of transmission in
      patients of chronic liver disease (CLD). DESIGN: A descriptive, non
      interventional study. PLACE AND DURATION OF STUDY: The study was conducted in the
      department of Medicine, Chandka Medical College Hospital, Larkana over a period
      of 6-year (January 1997-December 2002). PATIENTS AND METHODS: The study included
      1074 patients of chronic liver disease admitted to the department of medicine due
      to HCV. Their variables were recorded and analyzed. RESULTS: A total of 1074
      patients, comprising of 564 of chronic hepatitis (group I) and 510 of cirrhosis
      liver (group II) respectively were studied. The male to female ratio was 2:1 in
      both groups. Anti-HCV antibody was present in 51% in group I and 57% in group II.
      Use of syringes (62%) was an important risk factor. CONCLUSION: HCV is a leading
      cause of CLD. The leading risk factor identified is the use of contaminated
      syringes.

PMID- 15569554
TI  - Clinical and morphological evaluation of tuberculous peripheral lymphadenopathy.
AB  - OBJECTIVE: To analyze clinical presentations in patients of tuberculous
      peripheral lymphadenopathy. DESIGN: a descriptive observational study. PLACE AND
      DURATION OF STUDY: Department of Chest medicine, Jinnah Postgraduate Medical
      Centre and National Institute of Child Health from January to June 2002. SUBJECTS
      AND METHODS: Patients presenting with peripheral lymphadenopathy with the
      confirmed diagnosis of tuberculous were included in the study. The diagnosis of
      tuberculosis was made on finding acid fast bacilli on smear examination and / or
      histological demonstration of caseating epithelioid cell granulomas in the
      specimen obtained by fine needle aspiration cytology (FNAC) or excision biopsy.
      Patients in whom definite diagnosis of tuberculosis was not established on the
      basis of microscopy or histopathology examination were excluded from the study.
      History and physical examination findings were recorded on pre-designed proforma.
      RESULTS: the maximum number of patients (68.75 %) was in pediatric age group. The
      duration of illness was more than a year in 43.75% of the patients. Cervical
      region was the commonest affected in 70.83 % patients. In majority of cases
      (89.58 %) glands were multiple and in 66.7% glands were matted. In 83% cases
      diagnosis was achieved by FNAC subjected for cytology and acid fast bacilte (AFB)
      smear examination. CONCLUSION: In local setting tuberculous etiology should be
      strongly suspected in a young patient presenting with peripheral lymphadenopathy,
      with prolonged duration of illness, and involvement of cervical glands with
      multiple and matted appearance. FNA is a reliable tool of diagnosis.

PMID- 15569555
TI  - Factors affecting tuberculosis control : decision-making at the household level.
AB  - OBJECTIVE: To explore the factors influencing decision-making process at
      household level vis-a-vis decision to seek health care, decision regarding the
      type of care and the decision to continue treatment. DESIGN: Cross-sectional
      study. PLACE AND DURATION OF STUDY: Government TB Center, Rawalpindi, from 16th
      January 2002 to 28th February 2002. SUBJECTS AND METHODS: In total, 100 smear
      positive patients were included in the study. First questionnaire was
      administered to first 50 randomly selected patients. The ethnographic decision
      models (EDM) were developed from the responses. The second questionnaire, derived
      from these models, was administered to the second group of randomly selected 50
      patients to test the predictive ability of the EDM. RESULTS: Decision-making
      regarding treatment of tuberculosis was influenced by patients' knowledge about
      the disease itself as well as its severity, infectivity and curability. Close
      relatives were found to play a critical role at all the decision-making levels.
      The EDM developed on these results had 80-90% ability to predict the decision
      making in tuberculosis patients. CONCLUSION: Effective health education, easy
      accessibility to treatment centres and trained and motivated health care
      providers can go a long way in making national Tb control program a success.

PMID- 15569556
TI  - Management of macular pucker.
AB  - OBJECTIVE: To document the outcome of macular pucker surgery in terms of
      improvement of visual acuity. DESIGN: Interventional quasi experimental study.
      SETTING: Ophthalmology Department, Civil Hospital, Karachi. PATIENTS AND METHODS:
      Twenty-two patients with macular pucker underwent surgical repair. Pars plana
      posterior vitrectomy with epiretinal membrane peeling and internal limiting
      membrane peeling (maculorrhexis) was carried out. Postoperative follow-up was
      done for one year. Main outcome measure were visual acuity, causes and ocular
      complications. Data was analyzed using SPSS Version-10. Non-parametric sign test
      with chi-square statistic was used to compare the pre-operative and postoperative
      outcome. RESULTS: The macular pucker was successfully removed in 18 patients that
      revealed high statistical significance regarding improvement in visual acuity.
      Earlier, significant improvement (18 / 22 cases) was observed at three-month
      postoperative examination (p < 0.0001). Insignificant (9/22) postoperative
      complications were noted at six-month post-operative follow-up. Metamorphopsia
      was relieved in 18 patients. Ten patients developed cataract, 4 patients
      developed increased intra-ocular pressure (transient) and two patients developed
      retinal detachment. CONCLUSION: Pars plana posterior vitrectomy with epiretinal
      membrane peeling and internal limiting membrane peeling (maculorrhexis) can
      successfully remove macular pucker, improve vision and relieve metamorphopsia.

PMID- 15569557
TI  - Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the
      treatment of community -acquired pneumonia in children.
AB  - OBJECTIVE: To compare the clinical response to amoxicillin, cefuroxime and
      clarithromycin in the treatment of community-acquired pneumonia in children and
      to see the cost effectiveness of each treatment. DESIGN: Randomized clinical
      control trial. PLACE AND DURATION OF STUDY: Department of Pediatrics, Khyber
      teaching hospital, Peshawar, from October 2001 to February 2002. SUBJECTS AND
      METHODS: Patients between 3 to 72 months of age, admitted in the hospital with
      community acquired pneumonia, were randomly divided into three groups,1,2,3. They
      were started on amoxicillin, cefuroxime and clarithromycin respectively. The
      patients were assessed daily. If there was no clinical improvement at 48 hours
      the antibiotic was changed. ANOVA statistical test was applied to see the
      clinical response to the treatment in the three groups. Cost effectiveness of the
      treatment was compared. RESULTS: There was no statistical difference in the
      clinical response at 48 hours of initiating treatment and at discharge (p > 0.01
      each). The mean hospital stay in group 1 and 2 was 3.3 days and group 3 was 3.2
      days respectively (p > 0.01). Ninety-seven percent patients in group 1 and 3, and
      95% patients in group 2 showed clinical improvement. The cost of treatment of
      community acquired pneumonia for 8 days was Rs 496/-, 730/-, 1018/- for
      amoxicillin, clarithromycin and cefuroxime respectively. CONCLUSION: Amoxicillin
      was found the most cost effective followed by clarithromycin and cefuroxime
      respectively in the treatment of non-severe and severe community-acquired
      pneumonia.

PMID- 15569558
TI  - Changing trend in emergency surgery for perforated duodenal ulcer.
AB  - OBJECTIVE: To evaluate changes in the emergency surgery of the duodenal ulcer.
      DESIGN: Descriptive and analytical study. PLACE AND DURATION OF STUDY: Department
      of Surgery, Haydarpasa Numune Teaching and Research Hospital. Data of peptic
      ulcer patients, operated on between January 1975 and the end of 1999, were
      collected between 1990 and 2000, and analysed retrospectively in the first half
      of 2003. SUBJECTS AND METHODS: Hospital records of 523 surgically treated
      patients, with duodenal ulcer perforation, during the period of 25 years (1975
      1999) in the same surgical department, was retrospectively analysed. Changing
      aspects of emergency surgery of peptic ulcer disease, in the recent period, were
      determined in respect to number of operations per year and in the choice of
      operative methods. RESULTS: The average number of patients and emergency
      operations per year was 21. No significant change was observed during the study
      period. Elective operations gradually decreased in the last ten years, and none
      was performed in the last 4 years. On the other hand, 226 emergency interventions
      for duodenal ulcer perforation were performed in the last ten years and 84
      interventions in the last 4 years. Definitive anti-ulcer surgery was performed in
      42% of patients between 1985 and 1994. Simple closure of the perforation plus
      treatment with proton pump inhibitors and with anti-Helicobacter pylori
      medication was the method in 80% during the last year. CONCLUSION: Emergency
      surgery for perforated duodenal ulcer preserves its steady rate despite
      disappearance of elective operations after tremendous progress in medical control
      of peptic ulcer disease. There is an obvious return from definitive anti-ulcer
      surgery to simple closure of the perforation followed by antisecretory and
      antibacterial medication in the recent years.

PMID- 15569559
TI  - Necrotizing fasciitis: management and outcome.
AB  - OBJECTIVE: To observe the various clinical presentations of necrotizing fasciitis
      and evaluate their management and outcome. DESIGN: An observational descriptive
      study. PLACE AND DURATION OF STUDY: Surgical-c unit of Khyber Teaching Hospital,
      Peshawar, from July 2001 to June 2002. SUBJECTS AND METHODS: The study included
      20 patients of necrotizing fasciitis treated during this period. Age, gender,
      clinical presentation and predisposing factors were recorded. Pus was cultured
      and the isolated organism and their sensitivity identified. Management included
      broad-spectrum antibiotics, extensive and frequent debridements along with
      supportive measures. RESULTS: Common age group was 21-40 years with a male
      predominance. eight patients had necrotizing fasciitis of inguinoscrotal and
      perineal region, while 6 each had abdomen and 6 with necrotizing fasciitis of the
      limbs involvement. Factors predisposing to infection were diabetes in 5 patients,
      abscess in 6, trauma in 3 and surgery in 3 patients, while no specific cause was
      found in 3 cases. Escherichia (E. coli), Bacteroids, Enterococci and Streptococci
      were the commonest organisms isolated. All were sensitive to a combination of
      piperacillin and ampicillin. Debridements were done 1-5 times in most cases.
      Fifteen patients (75%) had complete recovery, 2 (10%) went to other hospitals on
      their own, 2 (10%) patients expired while one patient was referred to the plastic
      surgery unit. CONCLUSION: Necrotizing fasciitis has multiple etiology and
      predisposing factors. The bacteriology is poly microbial. Early presentation and
      diagnosis, supportive measures, broad-spectrum antibiotics, prompt and aggressive
      surgical debridements remains the cornerstone of management.

PMID- 15569560
TI  - Anesthetic management of lower tracheal reconstruction.
AB  - We report a case of 26 years old man who presented with dyspnoea and stridor in
      the emergency room. He was diagnosed as a case of posttracheostomy lower tracheal
      stenosis and scheduled for lower tracheal reconstruction. Patient was intubated
      in the operating room while breathing spontaneously. Due to proximity of stenosis
      to carina, a portex microlaryngeal tube was used to ventilate left lung during
      the period of tracheal resection.

PMID- 15569561
TI  - Segmental neurofibromatosis [NF type - v].
AB  - Segmental neurofibromatosis is a rare variant of neurofibromatosis in which skin
      lesions are confined to a circumscribed body segment. A case of a 39-year-old man
      with this condition is presented, who was having multiple soft skin tumours over
      a localized area of back with no associated cafe au lait spots, axillary freckles
      or lish nodules. Histology confirmed the diagnosis of neurofibroma.

PMID- 15569562
TI  - Bilateral treponema periostitis.
AB  - Symmetrical exuberant periostitis is a rare disease caused by variety of
      infectious and non-infectious causes. Treponematosis is one of the rare causes of
      this condition. We report a patient who presented with left arm swelling,
      secondary to onion peel periostitis of the humerus, which was caused by Treponema
      species.

PMID- 15569563
TI  - Duchenne muscular dystrophy with associated growth hormone deficiency.
AB  - A patient with Duchenne muscular dystrophy (DMD) and growth hormone (GH)
      deficiency is described who had no clinical evidence of muscular weakness before
      initiation of GH replacement therapy. Treatment with human GH resulted in
      appearance of symptoms of easy fatigability and proximal muscle weakness.
      Thorough investigations including serum creatinine phosphokinase (CK) levels is
      recommended in every patient with GH deficiency before starting GH replacement
      therapy.

PMID- 15569564
TI  - Mondor's disease of breast.
AB  - A case of Mondor's disease of breast in a 32 years old lady is described. She
      presented with painful vertical subcutaneous cords under her left breast. On
      scintimammography a suspicious nodule in her breast was detected, which revealed
      to be benign epithelial lesion on FNAC. With reassurance and placebo, the disease
      resolved spontaneously within two months.

PMID- 15569565
TI  - Structured feedback from students in tutorial teaching.

PMID- 15569566
TI  - An update on the diagnosis of tuberculosis.
AB  - Tuberculosis (TB) continues to be the bane of mankind. Early diagnosis is the
      cornerstone of tuberculosis control strategies. Recent years have seen major
      advances in the fields of biotechnology and molecular biology with introduction
      of several new diagnostic techniques for tuberculosis and improvement in the
      existing ones. The new automated culture techniques have appreciably reduced the
      time required for detection and antimicrobial susceptibility testing. The
      molecular amplification techniques like the Polymerase Chain Reaction (PCR) have
      made the same-day diagnosis a reality. Improvements in serology and introduction
      of novel new techniques like the bacteriophage assays have also shown a lot of
      promise. However, most of these new techniques are too expensive and
      sophisticated to be of any practical benefit to the vast majority of TB patients
      living in underdeveloped countries like Pakistan for whom an early and
      inexpensive diagnosis remains as elusive as ever. In this article various
      existing modalities as well as the new advances in TB diagnostics are reviewed.

PMID- 15569567
TI  - Frequency of anti-HCV antibodies in patients with lichen planus.

PMID- 15569569
TI  - Changes in the pattern of health disorders diagnosed among two cohorts of French
      travelers to Nepal, 17 years apart.
AB  - BACKGROUND: Few on-site studies involving local doctors have been published.
      METHODS: We conducted a prospective on-site study of health problems occurring
      among French tourists to Nepal between 1 January 2001 and 31 December 2001, and
      compared the results with those of an identical study performed in 1984. RESULTS:
      Of the 21,457 French tourists who visited Nepal in 2001, 276 (1.3%) consulted the
      French Embassy doctor in Kathmandu with health complaints. The main reasons for
      seeking medical advice were diarrhea (26.8%), high-altitude illness (15.6%),
      lower respiratory tract infections (11.6%), dermatoses (8.7%), and fever (8.7%).
      Fifteen patients (5.4%) required hospitalization, five required medical
      evacuation (1.8%), and 14 (5%) were rescued by helicopter in the Himalayas. One
      patient died of cardiovascular disease. Relative to the 1984 cohort,
      significantly more patients consulted for high-altitude illness (p<.001), lower
      respiratory tract infections (p=.001), physical trauma (p=.01), and psychiatric
      disorders (p<.001), and significantly fewer patients consulted for dermatoses
      (p=.04), sexually transmitted diseases (p=.001), and upper respiratory tract
      infections (p=.005). CONCLUSION: These results, obtained 17 years apart,
      illustrate the changes in the pattern of health disorders causing travelers in
      Nepal to consult a doctor.

PMID- 15569570
TI  - Quality of travel health advice in higher-education establishments in the United
      Kingdom and its relationship to the demographic background of the provider.
AB  - BACKGROUND: The number of international trips undertaken by residents of the
      United Kingdom has risen dramatically over the past 50 years. Likewise, the
      numbers studying in higher education have also shown a huge increase. This study
      aimed to assess the appropriateness of advice given to traveling students by
      higher education-based health services and to relate this to the demography and
      experience of the professionals involved. METHODS: A postal questionnaire
      describing three hypothetical groups of students traveling to different parts of
      the world was sent to 335 doctors and nurses. These clinicians belonged to the
      British Association of Health Services in Higher Education. They worked in 105
      practices that serve higher-educational establishments in the United Kingdom.
      Main outcome measures included whether appropriate immunizations were advised and
      given correctly through the National Health Service (NHS) or privately, and
      whether appropriate advice was given regarding malaria, human immunodeficiency
      virus (HIV), and miscellaneous risks. The sources of information used to advise
      travelers were also asked, and the effect of demographic characteristics of the
      respondents on the quality of advice was investigated. RESULTS: Two hundred
      fifteen (64%) questionnaires were returned. The mean score for whether the
      correct immunizations were advised was 77%, and for whether these were given
      correctly through the NHS or privately was 79.6%. For malaria, HIV, and
      miscellaneous risks, the scores were lower at 65%, 38%, and 32%, respectively.
      The score for correct immunizations was significantly affected by sex, with
      females respondents scoring higher (p = .036). Previous training in travel
      medicine improved scores for immunizations (p = .034) and for the correct choice
      being given through the NHS or privately (p = .006). Age, hours worked, role, and
      size of practice had no influence on scores. Charts in the general practice free
      newspapers were the most popular source of information. CONCLUSIONS: Practices
      serving higher-education establishments usually give appropriate advice to
      travelers in terms of the immunizations required, whether these are available
      through the NHS or privately, and about reducing risks of malaria. This is not
      the case regarding advice pertaining to HIV and miscellaneous risks. Previous
      training in travel medicine seems to correlate with the giving of more
      appropriate advice.

PMID- 15569571
TI  - Travel as a risk factor for malaria requiring hospitalization on a highland tea
      plantation in western Kenya.
AB  - BACKGROUND: Over the past two decades, endemic malaria returned to the western
      highlands of Kenya, a region that had been free of endemic malaria during the
      preceding 30 years. A study of malaria patients admitted to a tea estate hospital
      was conducted to estimate the risk of severe malaria when acquired during travel
      away from the tea estates compared with infections that had probably been locally
      acquired. METHODS: From May 1998 to March 2000, 1,296 patients were evaluated
      with a case-control design and standardized questionnaire during their
      hospitalization. Death certificates from the tea estates were examined from 1964
      to 1972 and 1986 to 1999. RESULTS: Travel away from the tea estates during the 2
      months prior to hospitalization (n = 432) was strongly associated with a
      diagnosis of malaria (odds ratio 2.7, 95% CI 2.1-3.5). The estimate of risk
      associated with travel was consistent with known malaria endemicity, the Rift
      Valley Province having a much lower malaria transmission than the area around
      Lake Victoria. The seasonality of malaria-related deaths indicates that many
      lowland-origin children probably contracted their fatal infection away from the
      tea plantation. CONCLUSIONS: Travel within Kenya is a significant risk factor for
      hospitalization owing to malaria on the tea estates; expatriate travelers need to
      be aware that the East African highlands cannot be regarded as malaria free.

PMID- 15569572
TI  - Airline crews' risk for malaria on layovers in urban sub-Saharan Africa: risk
      assessment and appropriate prevention policy.
AB  - BACKGROUND: The main aims of this study were to quantify the annual risk of
      falciparum malaria among nonimmune, UK-based airline crew and to undertake a risk
      assessment of short layovers in sub-Saharan African cities. METHODS: The number
      of nights exposed in malaria-endemic regions and reported cases of falciparum
      malaria were used to estimate annual disease incidence. Transmission risk
      estimates were calculated for each layover, that is, where crew were accommodated
      overnight, for one or more nights, in designated city hotels. Air-conditioning of
      ground transport, hotels, and airports was provided at all crew layovers. Details
      of activities associated with a risk for malaria and of adherence to antimosquito
      measures among crew were collected through a self-administered postal
      questionnaire. RESULTS: The annual risk of falciparum malaria was calculated to
      be 1.6 cases per 100,000 nights of exposure (95% CI 0.5-3.7). Crew reported
      widespread use of personal protection measures during the evenings when at risk.
      CONCLUSIONS: Attack rates of falciparum malaria were considerably lower than
      those reported in tourists during visits to sub-Saharan Africa. Factors
      contributing to this low attack rate included risk awareness, a protected
      sleeping environment, an urban setting, vector environmental controls, brief
      exposure, and good compliance with personal protection measures. Previously
      reported chemoprophylaxis compliance of < 10% in the same population was unlikely
      to have contributed to the low rate of disease. The longer layovers, of 3 or 4
      nights, in some East African rosters provided greater opportunity for
      discretionary leisure activity away from protected hotel environments, and this
      needs to be considered in a risk assessment.

PMID- 15569573
TI  - Interventions to prevent and control food-borne diseases associated with a
      reduction in traveler's diarrhea in tourists to Jamaica.
AB  - BACKGROUND: In 1996 a study found that approximately one in four tourists to
      Jamaica were affected with traveler's diarrhea (TD) during their stay. That year
      the Ministry of Health initiated a program for the prevention and control of TD.
      The aim of this ongoing program was to reduce attack rates of TD from 25% to 12%
      over a 5-year period by improving the environmental health and food safety
      standards of hotels. METHODS: Hotel-based surveillance procedures for TD were
      implemented in sentinel hotels in Negril and Montego Bay in 1996, Ocho Rios in
      1997, and Kingston in 1999. A structured program provided training and technical
      assistance to nurses, food and beverage staff, and environmental sanitation
      personnel in the implementation of Hazard Analysis Critical Control Point
      principles for monitoring food safety standards. The impact of interventions on
      TD was assessed in a survey of tourists departing from the international airport
      in Montego Bay in 1997-1998 and from the international airport in Kingston in
      1999-2000. The impact of the training and technical assistance program on food
      safety standards and practices was assessed in hotels in Ocho Rios as of 1998 and
      in Kingston from 1999. RESULTS: At the end of May 2002, TD incidence rates were
      72% lower than in 1996, when the Ministry of Health initiated its program for the
      prevention and control of TD. Both hotel surveillance data and airport
      surveillance data suggest that the vast majority of travelers to Kingston and
      southern regions are not afflicted with TD during their stay. The training and
      technical assistance program improved compliance to food safety standards over
      time. CONCLUSION: Interventions to prevent and control TD in visitors to Jamaica
      are positively associated with a reduction in TD in the visitor population and
      improvements in food safety standards and practices in hotels.

PMID- 15569574
TI  - Challenges for health and tourism in Jamaica.

PMID- 15569575
TI  - Long-term malaria prophylaxis for travelers.

PMID- 15569576
TI  - Leptospirosis with pulmonary hemorrhage, caused by a new strain of serovar Lai:
      Langkawi.

PMID- 15569577
TI  - Q fever in travelers: 10 cases.

PMID- 15569578
TI  - Doxycycline-induced photo-onycholysis.

PMID- 15569579
TI  - Eosinophilic meningitis caused by Angiostrongylus cantonensis: a case report and
      literature review.

PMID- 15569580
TI  - Selected bibliography.

PMID- 15569582
TI  - AAHB initiative to establish doctoral research competencies: a first step.

PMID- 15569583
TI  - Impact of an immunization education program on middle school adolescents.
AB  - OBJECTIVES: To raise middle school student awareness, attitudes, and proactive
      behaviors about immunization, and to increase immunization rates among middle
      school students through implementation of a comprehensive integrated immunization
      promotion curriculum (Immunization Plus!) METHODS: Evaluation used a quasi
      experimental non-equivalent comparison-groups design conducted in a sample of 40
      classrooms in 22 schools in California. RESULTS: Sixth-grade students exposed to
      the curriculum developed more positive knowledge and attitudes, and were more
      likely to be immunized, to intend to obtain newly required immunizations, and to
      tell parents about immunizations. CONCLUSION: Infectious disease control and
      immunizations are under-developed subject areas within school-based health
      promotion in the United States that can be effectively taught to middle school
      students.

PMID- 15569584
TI  - Exposure to televised alcohol ads and subsequent adolescent alcohol use.
AB  - OBJECTIVE: To assess the impact of televised alcohol commercials on adolescents'
      alcohol use. METHODS: Adolescents completed questionnaires about alcohol
      commercials and alcohol use in a prospective study. RESULTS: A one standard
      deviation increase in viewing television programs containing alcohol commercials
      in seventh grade was associated with an excess risk of beer use (44%),
      wine/liquor use (34%), and 3-drink episodes (26%) in eighth grade. The strength
      of associations varied across exposure measures and was most consistent for beer.
      CONCLUSIONS: Although replication is warranted, results showed that exposure was
      associated with an increased risk of subsequent beer consumption and possibly
      other consumption variables.

PMID- 15569585
TI  - Smoking-related correlates of depressive symptoms in low-income pregnant women.
AB  - OBJECTIVES: To investigate smoking-related correlates of depressive
      symptomatology in low-income pregnant women. METHODS: A cross-sectional survey of
      245 pregnant women who smoked prior to pregnancy. RESULTS: Women who had lower
      self-efficacy for maintaining abstinence both in positive affect/social
      situations and when experiencing negative affect demonstrated greater depressive
      symptomatology. Additionally, marijuana use, nicotine dependence, and general
      confidence in one's ability to quit smoking showed a positive relationship to
      depression. CONCLUSIONS: Several modifiable factors that can be targeted through
      behavioral and cognitive behavioral intervention strategies appear to influence
      the relationship between depression and smoking in low-income pregnant women.

PMID- 15569586
TI  - Association of body mass index to meeting physical activity recommendations.
AB  - OBJECTIVE: To investigate the association between BMI and physical activity based
      on the CDC-ACSM recommendation and a more demanding standard consistent with the
      IOM recommendation. METHODS: A random-digit-dialed survey (n=1810) used 2001
      BRFSS questions to measure physical activity. RESULTS: Data revealed a monotonic
      association between BMI and physical activity level. Lower odds of meeting both
      recommendations were associated with higher BMI. The proportion meeting the CDC
      ACSM recommendation was at least 3 times that of persons meeting the IOM-based
      recommendation. CONCLUSIONS: Meeting either recommendation was associated with
      BMI; however, a larger proportion of persons were meeting the less demanding CDC
      ACSM recommendation.

PMID- 15569587
TI  - Sun protection motivational stages and behavior: skin cancer risk profiles.
AB  - OBJECTIVE: To create skin cancer risk profiles that could be used to predict sun
      protection among Midwest beachgoers. METHOD: Cluster analysis was used with study
      participants (N=239), who provided information about sun protection motivation
      and behavior, perceived risk, burn potential, and tan importance. Participants
      were clustered according to their risk profiles; 4 distinct risk profiles
      emerged. RESULTS: Analyses revealed that risk profiles were significantly
      different on sun protection motivation and behavior and marginally different in
      terms of sun tanning behavior. CONCLUSION: Given the complexity of risk factors,
      an examination of clusters, rather than factors in isolation, may more accurately
      depict sun protection behavior.

PMID- 15569588
TI  - Motivation and reasons to quit: predictive validity among adolescent smokers.
AB  - OBJECTIVES: To examine reasons to quit among adolescents in a smoking cessation
      program, and whether reasons were associated with subsequent cessation. METHODS:
      Participants were 351 adolescents. At baseline, adolescents reported motivation,
      reasons to quit, and stage of change for cessation. Quit status was assessed at
      end of treatment. RESULTS: Girls were more likely to endorse image and appearance
      reasons to quit. Cessation was more likely among adolescents with higher
      motivation and those wanting to quit because of friends. CONCLUSIONS: Different
      reasons to quit were associated with motivation and cessation. Baseline
      motivation strongly predicted cessation, suggesting the relative value of
      assessing global motivation.

PMID- 15569589
TI  - State of the Academy presidential address 4th scientific conference - Sedona, AZ.
AB  - This state of the Academy address was presented at the opening ceremonies of the
      fourth annual scientific meeting of the American Academy of Health Behavior by
      the outgoing president of the Academy, February 29, 2004.

PMID- 15569590
TI  - Introduction of Cheryl L. Perry, recipient of the 2004 Research Laureate
      Medallion.

PMID- 15569591
TI  - Getting beyond technical rationality in developing health behavior programs with
      youth.
AB  - OBJECTIVE: To explore 2 major components of health behavior research, etiologic
      research and action research. To argue that action research is both an artistic
      as well as scientific process. METHODS: Review of the development process of
      effective health behavior programs with youth. Review of literature on art as
      part of the scientific process, especially in the field of education. RESULTS:
      Intervention programs that included explicitly creative components demonstrated
      success in reducing alcohol use and increasing healthful eating and activity
      patterns. CONCLUSIONS: Health behavior researchers might involve art and
      creativity in action research to enhance program retention and outcomes.

PMID- 15569593
TI  - Reactive oxygen species (ROS) induce chemical and structural changes on human
      insulin in vitro, including alterations in its immunoreactivity.
AB  - Oxidative stress occurs when the production of reactive oxygen species (ROS)
      exceeds the endogenous antioxidant defense. Peroxidations induced by ROS are the
      key of chemical and structural modifications of biomolecules including
      circulating proteins. To elucidate the effect of ROS on circulating proteins and
      considering the presence of oxidative stress in Diabetes Mellitus, the effects of
      ROS, in vitro, on human insulin were studied. We utilized the Fenton reaction for
      free hydroxyl radical (HO*) generation in presence of human recombinant insulin
      measuring chemical changes on its molecular structure. The induced changes in
      insulin were: a) significant increase on absorbance (280 nm) due to phenylalanine
      hydroxylation (0.023 +/- 0.007 to 0.13 +/- 0.07). b) Peroxidation products formed
      on amino acids side branches (peroxyl and alcohoxyl group); measured as increased
      capacity of reduce nitroblue of tetrazolium (NBT) to formazan (0.007 +/- 0.007 to
      0.06 +/- 0.02). c) Increased concentration of free carbonyl groups (8.8 +/- 8.7
      to 45.6 +/- 20.2 pmoles dinitrophenylhidrazones/nmol insulin) with lost of
      secondary structure, and d) Modification of epithopes decreasing the insulin
      antigen-antibody reactivity measured as a decrease in insulin concentration by
      RIA. In conclusion, the radical hydroxyl in vitro is able to induce molecular
      modifications on insulin.

PMID- 15569594
TI  - The role of interleukin-8 in cancer cells and microenvironment interaction.
AB  - Abstract Interleukin (IL)-8, a cytokine of the CXC chemokine family that was
      originally classified as a neutrophil chemoattractant, is now reported to play an
      important role in tumor progression and metastasis in a variety of human cancers,
      including lung cancers. IL-8 biologic activity in tumors and the tumor
      microenvironment may contribute to tumor progression through its potential
      function in the regulation of angiogenesis, cancer cell growth and survival,
      tumor cell motion, leukocyte infiltration and modification of immune responses.
      Recently, infiltrating macrophages in tumor stroma have been considered to be
      able to stimulate cancer growth, enhance angiogenesis and promote metastasis, and
      has prognostic significance in several human cancers. Accumulating evidence also
      shows that cancer cells and stromal cell interaction can stimulate cancer cells,
      as well as stromal cells in the expression of IL-8 and other growth factors.
      Here, we summarize current information about IL-8 biology in human lung cancers
      and focus on its effect on tumor angiogenesis, regulation of IL-8 expression in
      tumors, its prognostic significances, the role of tumor infiltrating macrophages
      in the production of IL-8 in cancer cells and the tumor microenvironment, gene
      expression profiles after cancer cell-stromal cell interaction, and the effect of
      a variety anti- inflammatory drugs on the modification of IL-8 and other gene
      expressions in cancer cells and the tumor microenvironment in lung cancers.

PMID- 15569599
TI  - Inhibition of Toll Like Receptor immune responses by microbial pathogens.
AB  - Toll Like Receptors (TLRs) are pathogen recognition receptors (PRRs) that respond
      to specific pathogen associated molecular patterns (PAMPs) during microbial
      invasion. After TLR stimulation a series of cellular responses initiate an
      inflammatory response and influence specific adaptive immunity that ultimately
      destroy the pathogen. But the immune response is not always able to control the
      infection. Pathogens have developed mechanisms to overcome and evade distinct
      arms of vertebrate immunity. Many of these strategies have been extensively
      described, but with the recent discovery of TLRs additional means to manipulate
      the innate immune response are currently being studied. Pathogens generally
      inhibit TLR mediated immunity by either blocking signals that stimulate further
      host defense mechanisms or by down-regulating their expression. These inhibitory
      mechanisms have been mainly elucidated in bacterial systems, whereas in other
      microorganisms they remain to be identified. Here the strategies that pathogenic
      microbes use to subvert TLR mediated immune responses are reviewed.

PMID- 15569600
TI  - Treating cancer with embryonic stem cells: rationale comes from aging studies.
AB  - In an earlier poster paper (1) we proposed that cancer can be viewed not only as
      a fatal disease but also as a local aberrant, rejuvenation, in an organism, and
      this fact can be useful for developing new anti-aging and anti-cancer treatments.
      In this paper we provide additional evidence from human and experimental animal
      studies in support of this view. First, we discuss cancer genes as candidate
      targets for anti-aging interventions. We review examples in which the life of
      experimental animals has been prolonged in situations of increased activity of
      proto-oncogenes - or decreased activity of tumor suppressors - in normal (non
      cancerous) cells in vivo. Studies of genetic polymorphisms revealed similar
      effects on longevity in humans. Second, we discuss the possibility of treating
      cancer with embryonic stem cells. The fact that cancer cells do not, age, means
      that these cells overcome aging host cells. However, cancer cells can be
      suppressed by young and quickly proliferating non-cancer cells, such as embryonic
      stem cells. The grafting of these cells in the tumor environment could be a
      prospective non-toxic anti-cancer treatment. We discuss recent evidence in
      support of this view.

PMID- 15569601
TI  - Synergism and complementarity between human CD1 AND MHC-restricted T cells, two
      lymphoid subsets directed against distinct antigenic worlds.
AB  - The antigenic repertoire of T cells has long been considered as exclusively
      composed of proteins and peptides. This view has been recently challenged by the
      discovery of CD1 molecules, a set of weakly polymorphic MHC class I-related
      receptors able to present lipid antigens to T cells. An updated picture of the
      biology of human CD1-restricted T cells is provided here, which highlights the
      unique features of these lymphoid effectors and the way they synergize with other
      innate and adaptive immune players to ensure protective immunity against tumors
      and pathogens.

PMID- 15569603
TI  - Tetracycline protects myocardium against ischemic injury.
AB  - Stress pretreatments protect myocardium from ischemic injury. We hypothesized
      that tetracycline, an antibiotic, may induce a stress response via the inhibition
      of mitochondrial translation as it induces the cold stress response by
      translational inhibition in E. coli. If so, tetracycline may protect myocardium
      from ischemic injury as stress pretreatments do. Thus, we investigated the
      effects of tetracycline on myocardial ischemia and its association with stress
      response. In a dog model of acute ischemia, 4mg/kg tetracycline injected 30 min
      prior to the occlusion improved the functional recovery from stunning of
      myocardium caused by ischemia. The same dosage of tetracycline dramatically
      reduced the size of infarct area in murine hearts analyzed by tetrazolium
      staining. In HeLa cells, tetracycline induced molecules that were increased by
      cold stress, which suggests that tetracycline may induce a cold stress-like
      response in mammalian cells. These molecules were also induced by ischemic stress
      in murine hearts, suggesting that the stress response caused by translational
      inhibition in mitochondria may be associated with the cardioprotection by
      tetracycline. Our results suggest that a subclinical dosage of tetracycline may
      protect heart from ischemic injury. Therefore, tetracycline may be of great use
      in suppressing the development of infarction caused by myocardial ischemia. This
      study is also important for providing new insights into the non-antimicrobial
      effects of tetracycline and its derivatives.

PMID- 15569604
TI  - The HTLV-I Tax oncoprotein: hyper-tasking at the molecular level.
AB  - HTLV-I is a complex retrovirus that encodes a transcriptional activator, Tax,
      which regulates expression of the viral promoter. Tax has been shown to be both
      necessary and sufficient to effect immortalization and transformation of cells in
      culture and tumorigenesis in animal models. Tax exerts its influence through
      protein-protein interactions with a variety of molecular targets, including
      transcription factors and cofactors, histone modifying enzymes and post
      translational modifying enzymes. Through these interactions, Tax disrupts
      cellular regulatory cascades and checkpoints designed to control a variety of
      systems. The result is untimely activation or repression of gene expression,
      inappropriate protein modifications, incorrect cell cycling, loss of adequate DNA
      repair capacity, and potential release of the cell from tumor suppression.
      Whereas for the virus these functions of Tax provide a means for successful
      completion of its life cycle, for the cell, they result at best in anarchy, and
      at worst in death of both the cell and the organism of which that cell is a part.

PMID- 15569605
TI  - The preclinical development of Medisorb Naltrexone, a once a month long acting
      injection, for the treatment of alcohol dependence.
AB  - Oral naltrexone, a nonselective opioid antagonist, is approved for the treatment
      of alcohol and opioid dependence. However, the efficacy of oral naltrexone is
      limited by poor patient compliance. To overcome this limitation, attempts have
      been made to develop an injectable extended-release formulation of naltrexone,
      including encapsulation into biodegradable polymer microspheres (e.g. Medisorb
      Naltrexone, Vivitrex (naltrexone long acting injection)). In 1980, NIDA
      established development goals that they considered optimal for an extended
      release formulation. At Alkermes, different formulations were tested with in
      vitro assays and in vivo models to select a lead formulation. Pharmacokinetic
      studies in rats confirmed that the principle formulation produced stable,
      pharmacologically relevant plasma levels of naltrexone for approximately one
      month following a single injection. The pharmacodynamic effects (antagonism of
      morphine analgesia) of extended-release naltrexone corresponded well with the
      pharmacokinetic profile from the same animals. While brain mu-opioid receptor
      density was found to increase over time in these rats, it did not appear to
      affect the ability of naltrexone to suppress morphine analgesia. Finally the
      pharmacokinetic profile of extended-release naltrexone in monkeys confirmed long
      duration of elevated plasma concentrations of naltrexone. Both naltrexone and the
      PLG polymer matrix in which it is encapsulated are well tolerated. Clinical
      trials of Vivitrex are currently ongoing in alcohol dependent patients.

PMID- 15569606
TI  - Dendritic cells in rheumatoid arthritis.
AB  - Dendritic cells are the most potent subset of antigen presenting cells. They are
      derived from bone marrow stem cells and reside in peripheral tissues or blood.
      Upon exposure to antigens and cytokines the peripheral DC s, express high amounts
      of peptide-MHC, and upregulate their costimulatory molecules, migrate to draining
      lymph nodes, and interact with T cells to stimulate or tolerize them. Dendritic
      cells have been found in synovium and joint fluid in rheumatoid arthritis, often
      at the center of a cluster of T cells. These DC s express MHC II, the
      costimulatory molecules CD40, CD80, CD86, adhesion molecules such as DC-SIGN and
      chemokine receptors such as CCR7. DC s can polarize T cells into Th1 or Th2
      phenotypes depending on the cytokine environment. Th1 responses are initiated in
      context of IL-12 and IL-23. The cytokine milieu of the RA synovium promotes DC
      differentiation and function that could lead to autoantigen presentation to T
      cells. Dendritic cells may be central to the pathogenesis of RA and could also be
      logical targets for treatment. DC s themselves could be used to deliver
      therapeutic gene products in autoimmune disease. DC s genetically modified to
      express IL-4 have been used to treat or prevent collagen arthritis in mice.

PMID- 15569607
TI  - Angiopoietin/Tie2 signaling, tumor angiogenesis and inflammatory diseases.
AB  - Mounting evidence demonstrates that the formation of new blood vessels, termed
      angiogenesis, plays critical roles in human disease development and progression.
      Based on these findings, there has been a tremendous effort to investigate the
      molecular mechanisms that drive blood vessel growth in adult tissues. Compared to
      physiological angiogenesis, inflammation is often accompanied with pathological
      angiogenesis and often is the underlying causes of many diseases such as cancer,
      arthritis, atherosclerosis, and others. Inflammation induces angiogenesis and
      reciprocally, angiogenesis facilitate inflammation. A study of the interaction
      between angiogenesis and inflammation will enhance our understanding of the
      mechanisms of diseases. It may generate novel approaches for therapy. Tie2 was
      recently identified as a receptor tyrosine kinase expressed principally on
      vascular endothelium, making it an attractive molecular target for angiogenic
      therapy. This review discusses the regulation of Tie2 and its angiopoietin ligand
      family in inflammation-associated angiogenesis focusing on cancer, arthritis, and
      atherosclerosis. The complexity of angiogenesis and context-dependent regulation
      of angiopoietin/Tie2 signaling in angiogenesis requires further studies.

PMID- 15569608
TI  - Inflammatory genes and neural activity: involvement of immune genes in synaptic
      function and behavior.
AB  - The function of pro-inflammatory cytokines and chemokines in brain injury and
      autoimmune diseases has been long recognized. There is however, a significant
      lack of information regarding the role of constitutively expressed immune genes
      in the normal brain. The current evidence points to the involvement of certain
      cytokines and major histocompatibility complex (MHC) molecules in synaptic
      function and plasticity. Furthermore, constitutively expressed chemokines in
      neurons provide an additional indication of a role for these molecules in neural
      function. In addition, clinical data suggests a dysregulation of immune genes in
      the cerebrospinal fluid of psychiatric patients who have neither brain injury nor
      autoimmune diseases. This review will discuss recent data indicating a role for
      immune genes in synaptic stability and will also discuss the implications for
      specific brain functions involving mood and cognition.

PMID- 15569609
TI  - TGF-beta signaling in chondrocytes.
AB  - Transforming growth factor-beta (TGF-beta) regulates a large variety of cellular
      activities. Binding of TGF- beta to its cell surface receptor triggers several
      signaling cascades, among which the TGF- beta -Smad pathway is the most
      extensively studied. TGF- beta also activates protein kinases, including MAPK,
      PKA and PKC, and modulates gene expression via its delicate interaction with
      other signaling pathways. During endochondral bone formation, TGF- beta acts as a
      potent inhibitor of the terminal differentiation of epiphyseal growth plate
      chondrocytes. This effect appears to be primarily mediated by Smad molecules,
      although MAPK-ATF2 signaling is also involved. The rate of chondrocyte maturation
      is tightly regulated through the interactions of Smad-mediated signaling, the Wnt
      signaling pathway, and the transcription factor Runx2. Improving our
      understanding of the exact mechanisms underlying TGF- beta -mediated signaling
      pathways and their effects may greatly impact the diagnosis and treatment of many
      common orthopaedic diseases.

PMID- 15569610
TI  - Critical role of R-loops in processing replication blocks.
AB  - Blocks in replication result from impediments to the advancing replication
      machinery and are lethal if not resolved. The replication fork must be
      reassembled for DNA synthesis to proceed. Fork assembly outside the chromosomal
      origin of replication (oriC) is mediated by recombination or via a helicase
      dependent pathway. ColE1 plasmid origins of replication and oriK sites initiate
      primosome assembly by an RNA-DNA hybrid structure known as R-loop. We review
      evidence suggesting that R-loops are frequent during normal cell growth and that
      R-loops are critical for the maintenance of genome integrity. We propose that
      downstream of a replication block, RNA at R-loops is extended by DNA polymerase
      I, opening up the DNA duplex and leading to the recruitment of the replisome.
      This would allow replication to proceed while the original block is repaired or
      bypassed. Unlike recombination and helicase-dependent fork restoration, this
      mechanism would operate preferentially in transcribed areas of the genome, which
      are known to be particularly susceptible to DNA damage. Our model emphasizes the
      intimate relationship between transcription and repair, offers a unifying
      interpretation of phenotypes attributed to bacterial strains deficient in R-loop
      fork assembly, and calls for a renewed focus on R-loop formation and regulation.

PMID- 15569611
TI  - Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in
      mammary cancer cells.
AB  - Tocopherols and tocotrienol represent the two subgroups within the vitamin E
      family of compounds, but only tocotrienols display potent anticancer activity at
      doses that have little or no effect on normal cell growth or function.
      Tocotrienols are potent antioxidants, but antitumor activity is independent of
      antioxidant activity. The exact reason why tocotrienols are more potent than
      tocopherols is not completely understood, but at least part of the reason is
      because of greater cellular accumulation. Furthermore, dose-response studies show
      that growth inhibitory doses of tocotrienols are 5-6 times lower than their
      corresponding lethal doses, suggesting that the antiproliferative and cytotoxic
      effects of tocotrienols are mediated through different mechanisms. Recent studies
      showed that tocotrienol-induced programmed cell death (apoptosis) results from
      the activation of specific intracellular cysteine proteases (caspases) associated
      with death receptor activation and signal transduction. Furthermore, combined
      treatment with specific caspase inhibitors blocked the cytotoxic effects of
      tocotrienols in malignant mammary epithelial cells. In contrast, tocotrienol
      inhibition of cell proliferation appears to involve the suppression of multiple
      hormone- and growth factor-receptor mitogenic signaling pathways. Although
      additional studies are required to clarify the intracellular mechanisms mediating
      the anticancer effects of tocotrienols, experimental evidence strongly suggests
      that dietary supplementation of tocotrienols may provide significant health
      benefits in lowering the risk of breast cancer in women.

PMID- 15569612
TI  - Neuropsychopathology in the SIV/macaque model of AIDS.
AB  - Of the 40 million people living with HIV/AIDS worldwide in 2003, only 7% received
      highly active antiretroviral treatment (HAART). Without treatment, approximately
      half of AIDS patients will suffer from NeuroAIDS including neurological
      dysfunction, peripheral neuropathies, motor impairment, cognitive difficulties
      and frank dementia. HAART has reduced mortality from AIDS in the developed world,
      but CNS/neurological complications continue to be a leading cause of death or
      disability in AIDS patients on HAART. Despite years of use in developed
      countries, it is still not clear what the long-term impact of HAART will be on
      NeuroAIDS. The mechanisms of AIDS-related CNS pathology, in the presence or
      absence of HAART, are not completely understood. Infection with simian
      immunodeficiency virus (SIV) in macaques provides an excellent research model of
      AIDS, including AIDS-related CNS pathology and cognitive/behavioral impairments.
      A major goal of research with the SIV/macaque model has been to characterize
      behavioral and cognitive impairments in NeuroAIDS and elucidate the CNS pathology
      behind these impairments. Review of the studies assessing cognitive impairment in
      SIV infected macaques demonstrates the high concordance between
      neuropsychological impairment in human and simian AIDS. Consistent with results
      in human AIDS patients, SIV-infected monkeys tend to be impaired most often on
      tasks dependent upon intact frontal cortical and/or subcortical functioning.
      Building on the strengths of the SIV/macaque model of AIDS, directions for future
      research are discussed including further mechanistic studies of the
      neuropathology leading to cognitive impairment as well as assessment of the
      impact of antiretroviral therapy or drugs of abuse on NeuroAIDS.

PMID- 15569613
TI  - Emerging roles of centrosomal amplification and genomic instability in cancer.
AB  - The carcinogenic process is multistep in terms of its etiology and multifactor in
      terms of its evolution. In this context, the temporal accumulation of multiple
      genetic changes during multistage carcinogenesis that can be mediated at least in
      part by genomic instability may represent crucial components of tumor cell
      evolution. Evidence is accumulating indicating a close link between genomic
      instability and cancer initiation and progression. Neoplastic cells typically
      possess numerous genomic lesions, which may include sequence alterations (point
      mutations, small deletions, and insertions) and/or gross structural abnormalities
      in one or more chromosomes (large-scale deletions, rearrangements, gene
      amplifications). Furthermore karyotypic alterations, including whole chromosome
      loss or gain, ploidy changes (aneuploidy and polyploidy) and a variety of
      chromosome aberrations are common in tumor cells. Genomic instability also
      involves mitotic defects associated with centrosome abnormalities. However, the
      question of whether abnormal centrosomes cause genomic instability or develop
      secondary to other changes has not been conclusively resolved. In this review,
      the recent studies investigating genomic instability and aneuploidy in human
      cancer, centrosome amplification and the role of centrosomal duplication in
      chromosomal mis-segregetion, and genes implicated in regulating chromosome
      segregation, centrosomal amplification and progression in cancer cells are
      discussed.

PMID- 15569614
TI  - HIV-1 mutagenesis during antiretroviral therapy: implications for successful drug
      treatment.
AB  - The evolution of antiretroviral drug resistance is a major problem in the
      treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy
      failure is associated with accumulation of mutations and results in the
      development of drug resistance. Drugs targeted against reverse transcriptase (RT)
      as well as drug-resistant RT have been shown to increase HIV-1 mutation
      frequencies. Furthermore, combinations of drug and drug-resistant RT can increase
      virus mutation frequencies in a multiplicative manner. The evolution of drug
      resistance also alters virus fitness. The correlation of increased HIV-1 mutation
      rates with the evolution of antiretroviral drug resistance indicates that drug
      failure could increase the likelihood of further resistance evolving from
      subsequent drug regimens. These observations parallel studies from microbial
      systems that provide evidence for a correlation between drug resistance
      development and increased pathogen mutation rates. Although increased mutant
      frequencies may be detrimental to effective therapy, the lethal mutagenesis of
      the HIV-1 genome may provide a new means for antiretroviral therapy.

PMID- 15569615
TI  - Semaphorins in cancer.
AB  - The semaphorins are the products of a large family of genes currently containing
      more than 30 members. These genes are divided into eight classes of which classes
      1, 2 and 8 contain invertebrate and viral semaphorins, while classes 3-7 contain
      the vertebrate semaphorins. The semaphorins have been implicated in diverse
      developmental processes such as axon guidance during nervous system development
      and regulation of cell migration. Plexin receptors function as binding and signal
      transducing receptors for all semaphorins except for the class-3 semaphorins
      which bind to neuropilins which subsequently activate signaling through
      associated plexins. The class-3 semaphorins semaphorin-3B (s3b) and semaphorin-3F
      (s3f) function additionally as potent inhibitors of tumor development in small
      cell lung carcinoma. Recent evidence indicates that these semaphorins modulate
      the adhesive and migratory properties of responsive malignant cells. S3f as well
      as semaphorin-3A (s3a) were also found to function as inhibitors of angiogenesis,
      and it was shown that the anti-angiogenic properties of s3f contribute
      significantly to its anti-tumorigenic properties. In contrast with these
      inhibitory semaphorins, there is some evidence indicating that semaphorins such
      as semaphorin-3C (s3c), semaphorin-3E (s3e), semaphorin-4D (s4d), semaphorin-5C
      (s5c) semaphorin-6A (s6a) and semaphorin-6b (s6b) may contribute to tumorigenesis
      or to tumor progression. In this review we discuss the semaphorins, their
      receptors and their signal transduction mechanisms, and evidence linking
      semaphorins to the control of tumorigenesis and tumor progression.

PMID- 15569616
TI  - Optimization of a multi-channel puffer system for rapid delivery of solutions
      during patch-clamp experiments.
AB  - In biological experiments, especially in neuroscience research, it is important
      to manipulate the extracellular environment efficiently. We have developed a
      micro-puffing system for local drug delivery to single cells in
      electrophysiological experiments, and validated the kinetic properties of this
      instrument. Based on our results, the kinetics of the delivery of solutions and
      the territory controlled by this system are influenced by several factors: (1)
      inner diameter (I.D.) of the guide tubing; (2) I.D. of the puffing tip; (3) angle
      of the puffing tip; and (4) gravity or external pressure applied to the solution.
      The system can fully control a territory of 200 x 600 micrometer2. The minimum
      delay in response to drug delivery is 10-20 ms. Switching between different
      solutions takes less than 100 ms. The minimum volume of solution required by the
      system is 0.2 ml. Taken together, our results provide useful data for designing
      and using an efficient drug/solution delivery system in electrophysiological
      experiments.

PMID- 15569617
TI  - Molecular aspects of vascular tissue engineering.
AB  - Cardiovascular disease remains the number one cause of death in the United
      States. Most current surgical procedures to alleviate this disease rely on the
      availability of suitable small diameter vascular grafts, which are constrained by
      several limitations. Tissue engineering brings new hope to this field, but still
      faces many challenges. This review focuses on the molecular aspects of the
      different components of vascular tissue engineering. The topics addressed include
      the cell type, extracellular matrix, and physical and biochemical stimulation
      with respect to their role in the development of a tissue engineered vascular
      graft.

PMID- 15569618
TI  - The L.E.A.P.S. approach to vaccine development.
AB  - The Ligand Epitope Antigen Presentation System (L.E.A.P.S.) approach to vaccine
      development utilizes immune peptides to promote the immunogenicity and influence
      the type of immune response generated towards epitopes in peptides which may be
      too small to elicit an immune response. The covalent attachment of these immune
      peptides to the antigenic peptide promotes the interaction of the epitope with T
      cells (T cell binding ligand (TCBL)) or antigen presenting cells (immune cell
      binding ligand (ICBL)) and ultimately promotes binding with the T cell receptor
      on CD4 or CD8 T cells. The, J, ICBL/TCBL peptide derived from the beta-2
      microglobulin chain of MHC I molecules promotes Th1 type responses to the
      antigenic peptide while the, G, ICBL/TCBL peptide derived from the beta chain of
      MHC II molecules promotes Th2 types of responses. The efficacy of this approach
      has been demonstrated by characterization of the immune responses to L.E.A.P.S.
      vaccines and by elicitation of protection from infectious challenge with herpes
      simplex virus and other pathogens. The protection studies show that the
      L.E.A.P.S. approach allows customization of the immune response appropriate for
      inducing protection from disease. The theory, background, examples and studies of
      the mechanism of action of the L.E.A.P.S. vaccines will be discussed.

PMID- 15569619
TI  - Absorption of myo-inositol hexakisphosphate (InsP6) through the skin: study of
      the matrix effects. mechanism of phytate topical absorption.
AB  - Myo-inositol hexakisphosphate (InsP6, phytate) is a molecule to which diverse
      beneficial properties have been attributed. Some of these properties are related
      to its dermatological use as discolouring agent, on preventing calcinosis cutis
      or due to its important role on premature aging. Other studies also seem to
      demonstrate a capacity of InsP6 to inhibit skin cancer. In this paper, the effect
      of the vehicle of topical administration of phytate is studied, using four groups
      of male Wistar rats (n = 6) fed with an InsP6 defficient diet and treated with a
      hydrophyl gel or an O/W moisturizing cream with two different concentrations of
      InsP6. Due to the correlation between InsP6 absorption and its urinary excretion,
      these last values were used to evaluate this process. It was found that phytate
      was absorbed through the skin using both a gel or a cream, demonstrating that its
      absorption is independent on the matrix used for topical treatment. However,
      urinary InsP6 values were slightly higher when using the gel, but in all cases
      values were much higher than those found with oral InsP6 treatment, due to the
      formation of insoluble species in the gastrointestinal tract when InsP6 is
      administered orally.

PMID- 15569620
TI  - Inhibition of calcium phosphate-DNA coprecipitates induced cell death by
      phosphocitrates.
AB  - Phosphocitrate [PC] is a powerful inhibitor of biological crystallization and a
      potential disease modifying drug for crystal associated diseases such as crystals
      associated osteoarthritis [OA]. Recently, it has been reported that a new PC
      complex salt, calcium sodium PC [CaNaPC], is much more powerful than its
      precursor, sodium PC [NaPC], in reducing the size of chemically-induced calcified
      plaques in rat when examined using a calcergy assay (1). The molecular mechanisms
      underlying such a superior activity as a calcification inhibitor over its
      precursor NaPC are currently unknown. In order to evaluate the potential of
      CaNaPC as a disease modifying drug for crystals associated OA, we examined and
      compared CaNaPC and its precusor NaPC using several cell- based assays. CaNaPC
      was found to have an inhibitory potency similar to that of NaPC toward preventing
      the stimulating effects of basic calcium phosphate [BCP] crystals on the
      induction of MMP1, thymidine uptake and endocytosis. However, CaNaPC proved much
      more powerful than NaPC in the inhibition of amorphous calcium phosphate-DNA
      coprecipitates-induced cell death. These results suggest that the superior anti
      calcification activity of NaCaPC over NaPC observed in rat is probably due to its
      superior activity in the inhibition of the effects associated with amorphous
      calcium phosphate clusters/aggregates/precipitates but not the effects associated
      with BCP crystals. Since amorphous calcium phosphate
      clusters/aggregates/precipitates are precursors of BCP crystals and coexist with
      calcium-containing crystals in calcified tissues (2-6), these amorphous
      clusters/aggregates/precipitates, similar to BCP crystals, may have played a
      significant role in pathological calcifications and in the development of
      crystals associated diseases such as crystals associated OA. The superior
      activity of CaNaPC over its precursor NaPC in the inhibition of amorphous calcium
      phosphate-DNA coprecipitates-induced cell death may, at least in part, explain
      its powerful anti-calcification activity in vivo. The findings suggest that
      CaNaPC through a dual action of inhibiting both the detrimental biological
      effects of formed BCP crystals and preforming amorphous calcium phosphate
      clusters/aggregates/precipitates, could present as a better disease-modifying
      drug for crystals associated OA than its parent NaPC.

PMID- 15569621
TI  - Positive and negative consequences of Fas/Fas ligand interactions in the
      antitumor response.
AB  - Understanding the mechanisms by which T lymphocytes mediate antitumor activity in
      vivo may have important implications for the design of active, adoptive and
      combination immunotherapies against neoplastic progression. The Fas/Fas ligand
      (FasL) system utilized by antigen (Ag)-specific T cells has been now demonstrated
      to play important roles in lymphocyte-mediated tumor regression in vivo. However,
      the process of tumor eradication by Fas/FasL interactions per se may serve also
      as an immune-based selective pressure. Indeed, more recent studies have
      illustrated that this same Fas/FasL system may have negative contributions,
      perhaps serving as a novel mechanism of tumor escape of Fas-resistant
      subpopulations. In addition to Fas-resistance, functional FasL expression by
      certain cancer cell types has been implicated in tumor escape via destruction of
      infiltrating Fas-bearing lymphocytes. Thus, the acquisition of Fas-resistance by
      advancing neoplastic subpopulations, possibly in combination with FasL induction
      may serve as countermeasures against immune attack and contribute favorably
      toward metastatic development. Further appreciation of the complex nature of this
      Fas/FasL system, exploited not only by innate or adaptive elements of the immune
      response, but also by a developing neoplasm may have important implications for
      the regulation of tumor progression in favor of clinical regression. Thus, this
      review will focus on both positive and negative consequences of the Fas/FasL
      system during host/tumor interactions. Emphasis will be on the importance of the
      Fas/FasL pathway for antitumor activity, as well as a potential selective force
      influencing the escape of Fas-resistant aggressive tumor variants.

PMID- 15569622
TI  - The role of matrix vesicles in growth plate development and biomineralization.
AB  - Skeletal cells control the initiation of mineralization in vivo and determine the
      selective distribution pattern of mineralization by releasing calcification
      initiating, submicroscopic, extracellular matrix vesicles (MVs) at selected sites
      in the extracellular matrix. The overall objective of this review is to outline
      what is currently known about the mechanisms of MV biogenesis and mineral
      initiation, while emphasizing recent observations that enhance our understanding
      of these mechanisms. Data from studies on the general mechanism of biogenesis of
      outer membrane vesicles and the formation and function of non-skeletal matrix
      vesicles is presented to stimulate thought concerning the possible biological
      functions that these structures may share with MVs.

PMID- 15569623
TI  - Identification of critical heterodimer protein interface parameters by multi
      dimensional scaling in euclidian space.
AB  - Protein subunit dimers are either homodimers (consisting of identical
      polypeptides) or heterodimers (consisting of different polypeptides). Protein
      dimers are involved in several cellular processes and an understanding of their
      molecular principle in complexations (subunit-subunit interaction) is essential.
      This is generally studied using 3D structures of homodimers and heterodimers
      determined by X-ray crystallography. However, the current knowledge on subunit
      interaction is limited due to lack of sufficient 3D dimer structures. It is our
      interest to study heterodimers using 3D structures to identify interaction
      parameters that would help in the development of a model to predict heterodimer
      interaction sites just from protein sequences. The efficiency of such models
      depends on the weighted contribution of numerous parameters characterizing
      heterodimer interfaces. Therefore, we studied the salient features of 111
      interface parameters in 65 heterodimer structures. In this study, we applied
      multi-dimensional scaling for dimensionality reduction on these parameters to
      select the most critical ones that best characterize heterodimer interfaces. The
      significance of these parameters in subunit interaction is discussed.

PMID- 15569624
TI  - Histone modifications as key regulators of transcription.
AB  - Covalent modifications of the amino-termini of the core histones in nucleosomes
      have been shown to be one of the key regulatory mechanisms in transcription
      regulation. Recently, new roles for histone modifications have been uncovered for
      the efficient functioning of RNA Pol II. Besides acetylation, which is the most
      characterized to date these modifications comprise phosphorylation, methylation,
      and ubiquitination. This review gives comprehensive view of all the major histone
      modifications and their effect on transcriptional regulation, in Saccharomyces
      cerevisiae.

PMID- 15569625
TI  - Immune evasion of the Lyme disease spirochetes.
AB  - The Lyme disease spirochetes, Borrelia burgdorferi sensu lato, have adapted very
      well to both surviving and persisting in the mammalian host despite a strong host
      antibody response. It appears that both temporal and spatial regulation of outer
      surface proteins have contributed to this persistence. The spirochetes are able
      to bind fH and FHL-1 to their surface, resulting in decreased complement
      activation. In addition, the organisms have taken advantage of components of tick
      saliva to aid in their initial immune evasion and dissemination. Studies leading
      to these conclusions are reviewed here.

PMID- 15569626
TI  - A framework to sub-type HLA supertypes.
AB  - The human leukocyte antigen (HLA) alleles are extremely polymorphic among ethnic
      population and the peptide binding specificity varies for different alleles in a
      combinatorial manner. However, it has been suggested that majority of alleles can
      be covered within few HLA supertypes, where different members of a supertype bind
      similar peptides, yet exhibiting distinct repertoires. Since the overlap between
      different members of a supertype appears to be extensive, it is crucial to
      develop a framework for grouping alleles into supertypes just from sequence
      information. In this report, we define sub supertypes, where members show
      functional overlap with identical repertoire, and describe a strategy to group
      HLA-A, B and C alleles into different categories of sub supertypes. The strategy
      grouped 47% of 295 A alleles, 44% of 540 B alleles and 35% of 156 C alleles to
      just 36, 71 and 18 groups, respectively. The grouping is moderately validated
      using available binding data. However, the validation is limited due to lack of
      binding data. Hence, the data presented in this article serve as a framework to
      test specific functional overlap between alleles. The grouping of HLA alleles
      into different categories of sub supertypes has profound use in the understanding
      of antigenic peptide selection, degeneration and discrimination during T-cell
      mediated immune response. A complete knowledge of this phenomenon finds utility
      in epitope design for the development of HLA based vaccines and immuno
      therapeutics.

PMID- 15569627
TI  - Functional protein-protein interaction of drug metabolizing enzymes.
AB  - Cytochrome P450 (P450, CYP), a major class of enzymes involved in Phase I drug
      metabolism, is expressed in the cellular endoplasmic reticulum together with
      other enzymes, such as microsomal epoxide hydrolase (mEH) and UDP
      glucuronosyltransferase (UGT). In many cases, the metabolite produced by P450 is
      sequentially metabolized by other enzymes to increase its water solubility. It
      would be reasonable to assume that the metabolite produced by P450 is directly
      transferred to the other enzymes participating in its subsequent metabolism via
      protein-protein interactions for rapid metabolism. However, these steps have been
      considered to take place individually. Previously, we suggested that CYP1A1
      specifically associates with mEH, UGTs and NADPH-P450 reductase. This observation
      strongly supports the view that there is functional cooperation between P450 and
      mEH/UGT to facilitate multistep drug metabolism. In recent years, accumulating
      evidence suggests the interaction between drug metabolizing enzymes and a change
      in enzymatic function by this interaction. In this review, we summarize the
      interaction between drug metabolizing enzymes and discuss its impact on their
      function.

PMID- 15569628
TI  - Role of ERK1/2 in FSH induced PCNA expression and steroidogenesis in granulosa
      cells.
AB  - Follicular development is characterized by both proliferation and differentiation
      of granulosa cells (GCs) under the control of FSH. However, the cellular
      mechanism by FSH is not known. Using cultured GCs, we examined whether FSH
      activated ERK1/2 was involved in the regulation of the proliferation related gene
      proliferating cell nuclear antigen (PCNA) and steroidogenesis. GCs were obtained
      from the ovaries of DES treated immature rats and cultured in serum free medium.
      The results showed that FSH activated ERK1/2 in a time dependent manner, with a
      peak at 20 min. Such activation was PKA dependent as was inhibited by specific
      inhibitors. FSH induced PCNA expression in a time dependent manner, with a
      maximum stimulation at 2 h. Similarly, StAR and steroid levels increased as FSH
      treatment time extended, with a maximum progesterone and StAR production at 48 h.
      ERK1/2 inactivation by UO126 inhibited the stimulatory effects of FSH on both
      PCNA and StAR expression and steroid synthesis in the GCs (p less than 0.01).
      Immunocytochemical studies further revealed that ERK1/2 inhibition led to a
      reduction of mitochondrial StAR in the GCs by FSH. These observations suggested
      that the stimulation of FSH on PCNA expression and steroidogenesis in GCs was
      mediated at least partially by ERK1/2.

PMID- 15569629
TI  - Use of Mg2+ and Ca2+ macroelectrodes to measure binding in extracellular-like
      physiological solutions.
AB  - Macroelectrodes designed to measure the extracellular free Mg2+ and Ca2+
      concentrations ([Mg2+]o, [Ca2+]o) may be used to determine Mg2+ and Ca2+ binding
      to extracellular buffers. This is important, as buffer concentrations may change
      physiologically or experimentally. A simplified calibration method allowed
      [Mg2+]o and [Ca2+]o > 50 micromol/l to be accurately measured. The method was
      used to determine the apparent dissociation constant, Kapp (+/- SD) of Mg2+
      binding to aspartate (22 degrees C, 101.7 +/- 22.5 mmol/l, n = 8; 44 degrees C,
      45.2 +/- 8.3 mmol/l, n = 6), citrate (high affinity, 0.33 +/- 0.14 mmol/l, n = 4;
      low affinity, approximately 80 mmol/l), malate (15.9 +/- 1.0 mmol/l, n = 7) and
      Ca2+ binding to malate (10.3 +/- 1.1 mmol/l, n = 7). Calculated and measured Kapp
      for Ca2+ binding to malate were only in agreement if the concept of ionic
      equivalent was used to adapt the tabulated constants to the experimental
      conditions. For Mg2+ binding to aspartate, malate and citrate there was no or
      only limited agreement with the calculated Kapp. These findings emphasise the
      difficulties involved in calculating free concentrations in biological solutions.
      It is concluded that it is more accurate to measure Kapp at the appropriate ionic
      strength and temperature.

PMID- 15569630
TI  - Setting the stage for transformation: HTLV-1 Tax inhibition of p53 function.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell
      leukemia and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM).
      Although the precise mechanism of HTLV-1 oncogenesis remains unclear, the
      pathogenesis has been linked to the pleiotropic activity of the viral
      transcriptional activator protein Tax. Tax has been shown to regulate viral and
      cellular gene expression and to functionally interfere with proteins involved in
      cell-cycle progression and DNA repair. This review will concentrate on the
      ability of Tax to promote cellular proliferation through activation of the NF
      kappaB pathway while inhibiting the cell-cycle checkpoint and apoptotic function
      of the tumor suppressor gene p53.

PMID- 15569631
TI  - Electrochemical determination of thiols at single-wall carbon nanotubes and PQQ
      modified electrodes.
AB  - The electrocatalytic oxidation of thiols has been observed at a glassy carbon
      (GC) electrode coated with a single-wall carbon nanotube (SWNT) film. Fourteen
      thiols including L-cysteine (CySH) and glutathione were tested using the SWNT/GC
      electrode, and the cyclic voltammetry (CV) showed that each thiol was oxidized at
      much less positive potential than those at other electrodes such as bare GC and
      diamond electrodes. The SWNT/GC electrode was also modified with pyrroloquinoline
      quinone (PQQ) which showed a further improvement of the catalytic behavior of the
      SWNT/GC electrode: e.g. the oxidation peak current of CySH was observed at 0.27 V
      vs. Ag/AgCl in pH 7.5 phosphate buffer. The amperometic responses at these
      electrodes showed a linear relationship with the substrate concentration in a 10(
      6)-10(-3) M range and 10(-6)-10(-7) M detection limits for several thiols
      including CySH, L-homocysteine, N-acetyl-L-cysteine, L-penicillamine and
      glutathione. These electrodes show a response time of 2-3 s and storage
      stabilities over 3 weeks. A PQQ/SWNT/GC electrode has been successfully applied
      for the assay of both L-cysteine and N-acetyl-L-cysteine in the dietary
      supplement.

PMID- 15569632
TI  - Senescence and its bypass in the vascular endothelium.
AB  - Vascular endothelial cells line the interior of blood vessels. As in other cell
      types, the proliferative lifespan of endothelial cells is limited; after a given
      number of replication cycles, they undergo senescence. Angiogenesis, the
      formation of new capillaries from pre-existing vasculature, is a process that
      involves endothelial cell proliferation. Angiogenesis thus has the possibility to
      be limited by the occurrence of senescence in the endothelial cell population.
      While there is evidence that endothelial cells undergo senescence in vivo, there
      are also data implying that endothelial senescence can be delayed or prevented in
      certain situations. Such a prevention of senescence would allow continued
      endothelial cell proliferation and continued angiogenesis in both physiological
      and pathological settings. This review discusses endothelial cell senescence and
      its bypass in vitro and in vivo.

PMID- 15569633
TI  - Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene
      disruption on the expression of enzymes involved in alcohol metabolism.
AB  - In alcohol metabolism, acetaldehyde, a highly reactive intermediate that may
      cause cellular and DNA damages, is converted to acetate by mitochondrial aldehyde
      dehydrogenase ALDH2. Although the majority of ingested alcohol is eliminated in
      the liver, the first-pass metabolism of ethanol in the upper digestive tract is
      also important for prevention and management of ethanol-related gastrointestinal
      diseases. However, the tissue-distribution of Aldh2 in mice has been poorly
      investigated. In this study, therefore, we investigated the tissue-distribution
      of Aldh2 as well as Aldh1, Cyp1a1, Cyp2e1, and Cyp4b1 in wild type and Aldh2-null
      mice by immuno-histochemical analysis. The human liver and esophageal tissues
      were also examined. In mice, the Aldh2 protein was detected in the liver, lung,
      heart, kidney, testis, esophagus, stomach, colon, and pancreas, suggesting that
      the tissue-distribution of Aldh2 in mice is similar to that in humans. Therefore,
      Aldh2-null mice may be useful model animals for the investigation of alcohol
      metabolism and related diseases. Compared with the wild type, the expression
      level of Cyp2e1 was increased in the liver from Aldh2-null mice based on Western
      blot analysis, whereas the levels of Aldh1, Cyp1a1, and Cyp4b1 were
      indistinguishable. This observation suggests that a metabolite(s) of Aldh2 might
      down-regulate the expression of Cyp2e1 gene.

PMID- 15569634
TI  - Multi-scale methodology: a key to deciphering systems biology.
AB  - Presently, it is widely accepted complex systems couldn't be comprehended by
      studying parts in isolation without examining integrative and emergent
      properties, and system-level understanding thus has become the focus in
      biological science. However, it should also be noted that common systematic
      analysis was restricted to large-scale analysis at a certain level, while the
      facts that the nature of complex systems is their multi-scale structures was
      usually neglected or ignored. Therefore, this paper described a multi-scale
      methodology to investigate the nature of biological complexity and prospected
      this methodology could lead to a promising revolution in current system-level
      understanding and the integration of molecular biology databases.

PMID- 15569635
TI  - Ligand epitope antigen presentation system vaccines against herpes simplex virus.
AB  - The Ligand Epitope Antigen Presentation System (L.E.A.P.S.) approach to vaccine
      development allowed construction of immunogens from defined T cell epitopes from
      herpes simplex virus (HSV) proteins that conferred protection against lethal
      challenge by the virus. This technology utilizes specific peptides which bind to
      CD4, CD8 or other proteins on the surface of T cells (T cell binding ligand
      (TCBL)), macrophage and dendritic cells (immune cell binding ligand (ICBL)) to
      promote the immunogenicity of an epitope, activate T cell and other protective
      responses, and direct the immune response to either a Th1 or a Th2 type of
      response. The J TCBL/ICBL is a peptide from beta-2-microglobulin which binds to
      the CD8 protein and promotes Th1 responses and the G TCBL/ICBL is a peptide from
      the beta chain of MHC II molecules that binds to the CD4 protein and promotes Th2
      responses. Epitopes from the ICP27 (H1, H2), glycoprotein B (gB) and glycoprotein
      D (gD) proteins of HSV-1 were attached to either the J TCBL/ICBL or the G
      TCBL/ICBL. The JH1, JH2, JgB and JgD vaccines elicited DTH responses without
      antibody but conferred protection upon lethal challenge. Th1 related antibody was
      produced after challenge of the JgB and JgD immunized mice. Immunization with the
      GH1, GgB or GgD vaccines did not yield protection. The GgB and GgD produced Th2
      related antibodies upon virus challenge. Initiation of the immune response by the
      JgD vaccine was dependent on functional CD4, CD8 expressing cells and interferon
      gamma and delivery of protection was dependent upon CD4 and interferon gamma. The
      L.E.A.P.S. HSV vaccines appear to elicit the appropriate immune responses for
      protection and further work is being performed to develop the JgD vaccine for
      human use.

PMID- 15569636
TI  - AKT/PKB signaling mechanisms in cancer and chemoresistance.
AB  - During the past decade, Akt (also known as protein kinase B, PKB) has been
      extensively studied. It regulates a variety of cellular processes by mediating
      extracellular (mitogenic growth factor, insulin and stress) and intracellular
      (altered tyrosine receptor kinases, Ras and Src) signals. Activation of Akt by
      these signals is via its pleckstrin homology (PH) domain binding to products of
      phosphatidylinositol 3-kinase (PI3K). This process is negatively regulated by a
      dual phosphatase PTEN tumor suppressor. Today, more than 30 Akt substrates have
      been identified. These phosphorylation events mediate the effects of Akt on cell
      survival, growth, differentiation, angiogenesis, migration and metabolism.
      Further, PI3K/PTEN/Akt pathway is frequently altered in many human malignancies
      and overexpression of Akt induces malignant transformation and chemoresistance.
      Thus, the Akt pathway is a major target for anti-cancer drug development. This
      review focuses on Akt signaling mechanism in oncogenesis and chemoresistance, and
      ongoing translational efforts to therapeutically target Akt.

PMID- 15569637
TI  - Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage.
AB  - Physiologic levels of extracellular PPi, which suppresses hydroxyapatite crystal
      growth, must be maintained by articular chondrocytes and resident cells in many
      othee tissues in order to prevent pathologic calcification. However,
      extracellular PPi rises in articular cartilage in direct association with aging.
      Matrix supersaturation with PPi stimulates chondrocalcinosis manifesting as
      calcium pyrophosphate dihydrate (CPPD) crystal deposition. Extracellular PPi
      levels are normally held in check by balances in PPi generation by nucleotide
      pyrophosphatase phosphodiesterase (NPP/NTPPPH) activity relative to PPi
      degradation by pyrophosphatases, by balance effects of cytokines and growth
      factors, and by transport of PPi from the cell interior involving the multiple
      pass transmembrane protein ANK. But these mechanisms become dysrgulated in aging
      and osteoarthritic (OA) cartilage and extracellular PPi excess supervenes,
      mediated in large part by upregulated NPP1 and ANK expression in articular
      cartilage. Conversely, NPP1 and ANK deficiency states were recently linked to
      phenotypically similar forms of spontaneous soft tissue calcification with
      hydroxyapatite (HA). Here, we focus on recent advances in understanding of PPi
      metabolism and NPP1 and ANK function pertinent to the pathogenesis of pathologi
      matrix calcification in articular cartilage.

PMID- 15569638
TI  - Second cancer risk, concomitant exposures and IRMER(2000).

PMID- 15569639
TI  - Second cancers following radiotherapy: a suggested common dosimetry framework for
      therapeutic and concomitant exposures.

PMID- 15569640
TI  - Pineapple juice as a negative oral contrast agent in magnetic resonance
      cholangiopancreatography: a preliminary evaluation.
AB  - The quality of magnetic resonance cholangiopancreatography (MRCP) images is
      frequently degraded by high signal from the gastrointestinal tract. The aim of
      this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent
      in MRCP. Preliminary in vitro evaluation demonstrated that PJ shortened T(2)
      relaxation time and hence decreased T(2) signal intensity on a standard MRCP
      sequence to a similar degree to a commercially available negative contrast agent
      (ferumoxsil). Electrothermal atomic absorption spectrometry assay demonstrated a
      high manganese concentration in PJ of 2.76 mg dl(-1), which is likely to be
      responsible for its T(2) imaging properties. MRCP was subsequently performed in
      10 healthy volunteers, before and at 15 min and 30 min following ingestion of 400
      ml of PJ. Images were assessed blindly by two Consultant Radiologists using a
      standard grading technique based on contrast effect (degree of suppression of
      bowel signal), and image effect (diagnostic quality). There were statistically
      significant improvements in contrast and image effect between pre and post PJ
      images. There was particularly significant improvement in visualization of the
      pancreatic duct, but no significant difference between 15 min and 30 min post PJ
      images. Visualization of the ampulla, common bile duct, common hepatic and
      central intrahepatic ducts were also significantly improved at 15 min following
      PJ. Our results demonstrate that PJ, may be used as an alternative to
      commercially available negative oral contrast agent in MRCP.

PMID- 15569641
TI  - In search of an unknown primary tumour presenting with extracervical metastases:
      the diagnostic performance of FDG-PET.
AB  - A retrospective study was carried out to determine the performance of 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with
      unknown primary tumours presenting with metastases external to the neck. All
      patients referred to an academic PET centre (July, 1997 to December, 2000)
      presenting with an extracervical metastasis and no prior systemic therapy were
      eligible. The minimum follow-up period was 11 months. From 63 eligible cases,
      known metastases were FDG avid in all but one neuroendocrine process. PET scans
      were retrospectively classified as positive for a primary tumour (n=29), i.e.
      revealing at least one anatomical site suspected to be the primary tumour. This
      was confirmed in 16, either by histology (n=10) or radiological and clinical
      follow-up (n=6). There were four false positive cases. In nine patients, the
      primary tumour was never confirmed. Of the remaining 33 negative PET scans the
      primary tumour was clinically not found in 18. Follow-up and additional pathology
      investigations demonstrated the primary tumour in 15. A survey on clinical
      usefulness of PET (response rate 83%) suggested that PET positively contributed
      to diagnostic understanding in 29 of 52 evaluable cases. Applied late in the
      diagnostic trajectory, approximately four patients need to be scanned by PET in
      order to find one primary tumour. However, in addition to direct demonstration of
      unknown primaries, there appears to be a positive effect on the diagnostic work
      up of these patients of a similar magnitude.

PMID- 15569642
TI  - The role of infrapopliteal angioplasty.
AB  - Infrapopliteal percutaneous transluminal angioplasty (PTA) is currently indicated
      in patients with critical limb ischaemia (CLI). It may be performed after femoral
      angioplasty or bypass surgery, to improve outflow and hence patency of the
      proximally treated segment. Patients with CLI are typically elderly with multiple
      co-morbidities and limited life expectancy and therefore, a procedure, which is
      minimally invasive with reduced morbidity and mortality but lesser long-term
      patency, may be more appropriate than a more invasive procedure with better long
      term patency. Clinical success is superior to angiographic patency, because once
      healing has occurred, should the artery restenose or occlude, collateral flow can
      be sufficient to preserve tissue integrity if there is no further injury.
      Although no prospective randomized trials have been performed, the reported limb
      salvage rates of PTA are comparable with surgery. As PTA carries a lower
      morbidity and mortality, shorter hospital stay and does not preclude surgery, it
      is ideal for this group of patients who are high-risk surgical candidates.
      Improvements in guide-wire and catheter technology and recanalization techniques
      mean that very long stenoses or occlusions, and multiple lesions can be treated
      successfully. At the current time, PTA is the treatment of choice for
      infrapopliteal occlusive disease; experience with the use of stents in this
      territory is increasing but currently insufficient to justify their primary use.

PMID- 15569643
TI  - Neuroradiological findings of intracranial schwannomas not arising from the stems
      of cranial nerves.
AB  - Four cases of intracranial schwannomas not arising from the stems of cranial
      nerves are reported. All cases were confirmed by surgery and pathological
      examination. The related histogenesis and the CT and MRI findings are discussed,
      and the literature is reviewed. The CT and MRI findings of these tumours were
      analysed retrospectively and their pathological characteristics were reviewed.
      The tumours presented as heterogeneous hypointense to isointense mixed dense
      lesions with multiple areas of cystic degeneration and necrosis. Extensive cystic
      degeneration was the prominent characteristic on CT. The tumours showed
      hypointense to isointense signal on T(1) weighted images and heterogeneous
      hyperintense signal on T(2) weighted images. On contrast enhanced CT and MRI, the
      solid component and the wall of the tumours showed moderate to strong
      enhancement. Haematoxylin and eosin staining of the lesion demonstrated two
      histological patterns, Antoni type A and Antoni type B. Immunostaining showed
      intense immunoreactivity for S-100 protein. The CT and MRI findings of these
      tumours were similar to those of schwannomas arising from cranial nerves,
      although the former show a higher rate of cystic degeneration. Therefore, even
      when a mass is not in the usual cranial nerve region, if its imaging
      characteristics are similar to those of common schwannomas, the possibility of a
      schwannoma not arising from cranial nerve should be considered.

PMID- 15569644
TI  - Patient radiation doses during invasive cardiac procedures categorised by
      clinical code.
AB  - Patient radiation doses delivered during invasive fluoroscopic cardiology
      procedures at the University Hospital of North Staffordshire during a 3 year
      period from November 1999 to August 2002, and comprising 6189 patient records,
      have been analysed. Cases have been stratified using classification codes from
      the Office of Population Census and Surveys (OPCS-4 codes), allowing
      representative doses to be assessed for 34 distinct types of cardiac radiological
      procedure. In addition, local guidance levels have been derived for the eight
      most common procedures. This work represents one of the largest and most detailed
      published studies of patient radiation dose during cardiac procedures, and should
      assist in meeting the IR(ME)R regulations requirement for establishment of
      diagnostic reference levels, and in enabling dose optimization of individual
      exposures.

PMID- 15569645
TI  - Radioprotective effect of abana, a polyherbal drug following total body
      irradiation.
AB  - Effects of 20 mg/kg body weight of abana (ABE) on radiation-induced sickness and
      mortality in mice exposed to 7 Gy to 12 Gy of gamma irradiation were studied.
      Treatment of mice with abana 1 h before irradiation delayed the onset of
      mortality and reduced the symptoms of radiation sickness when compared with the
      non-drug treated irradiated controls (double distilled water, DDW). Abana
      provided protection against both the gastrointestinal and haemopoietic deaths.
      However, animals of both the ABE+irradiation and DDW+irradiation groups did not
      survive up to 30 days post-irradiation beyond 11 Gy irradiation. The LD(50/30)
      was found to be 8.5 Gy for the DDW+irradiation group and 10.3 Gy for
      ABE+irradiation group. The administration of abana resulted in an increase in
      radiation tolerance by 1.8 Gy, and the dose modification factor (DMF) was found
      to be 1.2. The irradiation of animals resulted in a dose dependent elevation in
      lipid peroxidation, and a reduction in glutathione (GSH) concentration on day 31
      post-irradiation. Treatment of mice with abana before irradiation caused a
      significant depletion in lipid peroxidation followed by a significant elevation
      in GSH concentration in the liver of mice at day 31 post-irradiation. Abana
      scavenged (*)OH, DPPH, ABTS(*+) and NO(*) in a concentration dependent manner in
      vitro. Our results indicate that the radioprotective activity of abana may be due
      to free radical scavenging and increased GSH level in irradiated mice.

PMID- 15569646
TI  - Usefulness of MRI in detecting occult breast cancer associated with Paget's
      disease of the nipple-areolar complex.
AB  - MRI allows for the detection of mammographically and clinically occult breast
      neoplasms. We analysed the ability of MRI to detect occult breast cancer in three
      patients with Paget's disease of the nipple-areolar complex, proven
      histologically. In all three cases we observed differences in the morphological
      and dynamic features of healthy and pathological nipples, and we also found
      enhancement foci in breast tissue, with suspicious kinetic and morphological
      characteristics, which in the case of two patients corresponded to ductal
      carcinoma in situ. The detection and location with MRI of underlying neoplastic
      foci may be of help in choosing the most reasonable and conservative treatment in
      these patients.

PMID- 15569647
TI  - Lipiodol UF retention in dental sialography.
AB  - Lipiodol is a lipid based contrast medium and is very useful in sialography. It
      gives very fine images and clearly shows the details of the gland. It is viscous
      and has a relatively high iodine content. However, lipiodol UF drops sometimes
      remain in the salivary gland and in the adjacent tissues for a long time and may
      cause irritation. We report a case where lipiodol UF leaked from Stensen's duct
      and was not resorbed after a period of 70 months.

PMID- 15569648
TI  - The CT halo: a new sign in active pulmonary sarcoidosis.
AB  - A case of pulmonary sarcoidosis is presented characterized by multiple coalescent
      nodules and peripheral ground glass halos, which were fully reversible under
      repeat systemic glucocorticoid treatment. The differential diagnostic aspects of
      the pulmonary CT halo sign and its potential for indicating active reversible
      disease in patients with sarcoidosis is discussed.

PMID- 15569649
TI  - Extraskeletal Ewing's sarcoma of the parapharyngeal space.
AB  - Extraskeletal Ewing's sarcoma (EES) is rarely found in the head and neck region.
      We report here a case of EES of the parapharyngeal space in a 53-year-old man who
      presented with blurred vision, dysphagia, hoarseness and right facial numbness.
      CT examination showed a large, seemingly well-defined soft tissue mass in the
      right parapharyngeal space with skull base destruction and intracranial
      extension. The patient showed poor response to chemotherapy and radiotherapy and
      died 6 months after initial presentation. A review of the literature revealed no
      previous reports of EES occurring in the parapharyngeal space.

PMID- 15569650
TI  - Primary melanoma of the oesophagus well palliated by radiotherapy.
AB  - A case of a 16 cm primary melanoma of the mid oesophagus in a Caucasian male is
      reported. Radiological investigations at presentation revealed asymptomatic
      mediastinal and lower oesophageal metastases. The patient was treated with
      hypofractionated radiotherapy and achieved durable local disease control and
      excellent palliation of his dysphagia and chest pain until his death from
      widespread metastatic disease 5 months after treatment. The role of external beam
      radiotherapy in the treatment of primary oesophageal melanoma is reviewed.

PMID- 15569651
TI  - Reverse echelon node and a lymphatic ectasia in the same patient during breast
      lymphoscintigraphy: the importance of injection and imaging technique.
AB  - Lymphoscintigraphy, along with triangulated patient body marking, can serve as a
      guide for surgeons during sentinel lymph node harvesting. Unique drainage
      patterns have been noted, especially with areolar or intradermal based
      injections, which are becoming increasingly popular. The images
      lymphoscintigraphy provide have been invaluable in delineating these patterns.
      The authors present a case that simultaneously illustrates two separate points in
      the same patient, a reverse echelon node and a lymphatic ectasia. To our
      knowledge, this combination has never been described in the same patient.
      Perilesional and areolar-cutaneous junction injections were performed
      sequentially and generated these patterns that could potentially have resulted in
      added morbidity and a false-negative sentinel node if not realised before
      surgery. Lymphoscintigraphy added valuable information in the management of this
      patient, which can occasionally present with complex patterns of activity during
      sentinel node harvesting.

PMID- 15569652
TI  - Orbital emphysema: an unusual complication of balloon dacryocystoplasty.
AB  - Balloon dacryocystoplasty is a procedure used in the treatment of partial
      nasolacrimal duct obstruction. A case of orbital emphysema following one such
      procedure is reported here. The risk factors associated with this rare event are
      highlighted.

PMID- 15569653
TI  - Magnetic resonance cholangiography in children.
AB  - Magnetic resonance cholangiography has been shown to be useful in the evaluation
      of hepatobiliary problems in paediatric patients. Its clinical application in
      biliary atresia, choledochal cyst, cholelithiasis, bile plug syndrome and liver
      transplant are illustrated by the following cases.

PMID- 15569656
TI  - Fibre-supplemented tube feeding in the hospitalised elderly.
AB  - OBJECTIVES: To evaluate the effect of fibre supplementation in enteral feeding on
      bowel function in hospitalised geriatric patients, and to assess its metabolic
      and nutritional efficiency. DESIGN: Prospective randomised controlled trial with
      stratification for diabetes. SETTING: Department of Geriatrics at the University
      of Antwerp. SUBJECTS: During 30 months (January 2000-June 2002) every
      hospitalised patient requiring tube feeding was assessed for eligibility (n =
      183). Finally 172 patients (19% diabetics) were randomised. METHODS: An enteral
      nutritional regimen consisting of 30 kcal/kg in 2000 ml with a calorie/nitrogen
      ratio of 156 with or without fibre was instituted. At weekly intervals, stool
      output was qualitatively evaluated by recording frequency, volume (small <1/2
      cup, large >1/2 cup) and consistency (solid-formed, soft-pasty or liquid-watery).
      Nutritional and metabolic effects were evaluated through laboratory analysis.
      RESULTS: Overall mortality was 24% with a trend for excess mortality in diabetic
      patients (33.3% versus 21.6% in non-diabetics; P = 0.176). There was no
      difference in duration of feeding between the fibre group (27.5 days; 95% CI =
      19.1-35.9) and the no fibre group (27.9 days; 95% CI = 20.2-35.5). In the fibre
      supplemented group, stool frequency was lower (4.1 per week; 95% CI = 3.7-4.6)
      than in controls (6.3 per week; 95% CI = 5.6-6.9). Qualitatively, stool
      consistency was higher (P < 0.001) but no difference in volume was noted. There
      were no differences in final laboratory parameters between groups. CONCLUSIONS:
      Fibre supplementation improved bowel function with reduced stool frequency and
      more solid stool consistency. It did not affect the nutritional efficiency of
      enteral feeding in hospitalised geriatric patients. Diabetes may be a risk factor
      for mortality in malnourished patients requiring tube feeding.

PMID- 15569660
TI  - Commentary: Maternal calcium intake and offspring cardiovascular risk factors.

PMID- 15569661
TI  - Maternal calcium supplementation and cardiovascular risk factors in twin
      offspring.
AB  - BACKGROUND: There is evidence that maternal calcium supplementation may result in
      lower offspring blood pressure. We hypothesized that maternal calcium
      supplementation also influences other cardiovascular risk factors. METHODS: In
      the Tasmanian Infant Health Study, supplements reportedly taken in pregnancy were
      recorded. Twin children of 147 participating mothers were seen at mean age 9
      years. Blood pressure was measured in all 294 children and fasting blood samples
      taken from 230 (78%) for glucose and insulin, triacylglycerol, total cholesterol
      (T-C) and HDL cholesterol (HDL-C). LDL cholesterol (LDL-C) was calculated.
      RESULTS: Children of supplemented mothers (n = 110, 77 had venipuncture) had
      lower geometric mean triacylglycerol, T-C, and LDL-C than other children. After
      adjustment for potential confounding factors, geometric mean ratios were 0.86
      (95% CI: 0.75, 0.98), 0.94, (95% CI: 0.90, 0.99) and 0.90, (95% CI: 0.83, 0.98)
      respectively. The association with T-C and LDL-C was seen principally among
      children with BMI > 17.5: estimated ratios 0.85 (95% CI: 0.79, 0.92) for total
      cholesterol and 0.79 (95% CI: 0.70, 0.90) for LDL cholesterol (P for interaction
      0.001 and 0.009 respectively). There was no significant association between
      maternal calcium supplementation and child size at birth and follow up, blood
      pressure, fasting glucose or insulin or HDL-C. CONCLUSIONS: Maternal calcium
      supplementation may confer health benefits on twin offspring, especially if they
      are relatively fat. Calcium availability could permanently programme lipid
      metabolism during fetal life, directly or by influencing maternal lipid profile.
      Our findings need to be replicated in other studies and in singletons. If
      confirmed, our findings could have important implications for population health.

PMID- 15569662
TI  - Childhood mortality and probable causes of death using verbal autopsy in Niakhar,
      Senegal, 1989-2000.
AB  - BACKGROUND: In African rural settings, medically certified information on causes
      of death is largely lacking. The authors applied the verbal autopsy to identify
      causes of death before 15 years old in a rural area of Senegal where a
      demographic surveillance system is operating. METHODS: Between 1989 and 2000, a
      postmortem interview was conducted using a standardized questionnaire which was
      independently reviewed by two physicians who assigned the probable underlying
      cause of death. Discordant diagnoses were discussed by a panel of physicians.
      Causes of death were grouped into a few categories; cause-specific mortality
      rates and fractions were generated. RESULTS: Between 1989 and 1997, all-cause
      mortality fluctuated. Diarrhoeal diseases, malaria and acute respiratory
      infections explained between 30% and 70% of the mortality before 10 years of age.
      In children 1-9 years old, malaria death rate increased between 1989 and 1994 and
      thereafter did not change. The 1998-2000 years were marked by a peak in
      mortality, attributed to a meningitis outbreak in children more than one year old
      paralleled by an increase in death rate from fever of unknown origin, diarrhoeal
      diseases, and acute respiratory infections in children under 5 years.
      CONCLUSIONS: Verbal autopsy provided useful information on the mortality
      structure responsible for the 1998-2000 peak in mortality. It underlined that,
      outside outbreak situations, malaria was a leading cause of death for 1-9 year
      old children and that diarrhoea, acute respiratory infections, or fever from
      unknown origin accounted for up to 50% of the deaths among the children under 5
      years.

PMID- 15569663
TI  - Mutations in the pore region modify epithelial sodium channel gating by shear
      stress.
AB  - Previous studies have shown that epithelial Na+ channels (ENaCs) are activated by
      laminar shear stress (LSS). ENaCs with a high intrinsic open probability because
      of a mutation (betaS518K) or covalent modification of an introduced Cys residue
      (alphaS580C) in the pre-second transmembrane domain (pre-M2) were not activated
      by LSS, suggesting that the pre-M2 region participates in conformational
      rearrangements during channel activation. We examined the role of the pore region
      of the alpha-subunit in channel gating by studying the kinetics of activation by
      LSS of wild-type ENaC and channels with Cys mutations in the tract Ser576-Ser592.
      Whole cell Na+ currents were monitored in oocytes expressing wild-type or mutant
      ENaCs prior to and following application of LSS. Following a 2.2-s delay, a
      monoexponential increase in Na+ currents was observed with a time constant (tau)
      of 8.1 s in oocytes expressing wild-type ENaC. Cys substitutions within the alpha
      subunit in the tract Ser580-Ser589 resulted in: (i) a reduction (Ser580-Trp585,
      Gly587) or increase (Ser589) in delay times preceding channel activation by LSS,
      (ii) an increase (Gln581, Leu584, Trp585, Phe586, Ser588) or decrease (Ser589) in
      the rate of channel activation, or (iii) a decrease in the magnitude of the
      response (Ser583, Gly587, Leu584). Cys substitutions at a putative amiloride
      binding site (alphaSer583 or betaGly525) or within the selectivity filter
      (alphaGly587) resulted in a reduction in the LSS response, and exhibited a
      multiexponential time course of activation. The corresponding gamma-subunit
      mutant (alphabetagammaG542C) had a minimal response to LSS and exhibited a high
      intrinsic open probability. These data suggest that residues in the pore region
      participate in the sensing and/or transduction of the mechanical stimulus that
      results in channel activation and are consistent with the hypothesis that the
      ENaC pore region has a key role in modulating channel gating.

PMID- 15569664
TI  - Signal-dependent binding of the response regulators PhoP and PmrA to their target
      promoters in vivo.
AB  - Low Mg2+ promotes phosphorylation of the response regulators PhoP and PmrA and
      transcription of their activated genes in Salmonella enterica. Using chromatin
      immunoprecipitation, we have now determined that the PhoP and PmrA proteins are
      recruited to the regulatory region of their target genes when bacteria experience
      low Mg2+ but not when they are grown in high Mg2+. Even when the PhoP protein was
      artificially produced at 4-fold higher levels than the wild-type strain, promoter
      occupancy required the low Mg2+ signal. Substitution of the predicted
      phosphorylation site Asp-52 with a valine residue abolished phosphorylation of
      the PhoP protein, resulting in loss of PhoP binding to target promoters and
      transcription of PhoP-activated genes. Our results indicate that the promoter
      binding ability of the PhoP and PmrA proteins occurring in low Mg2+ is correlated
      with phosphorylation of these proteins in vivo.

PMID- 15569665
TI  - Lithium can relieve translational repression of TOP mRNAs elicited by various
      blocks along the cell cycle in a glycogen synthase kinase-3- and S6-kinase
      independent manner.
AB  - TOP mRNAs are translationally controlled by mitogenic, growth, and nutritional
      stimuli through a 5'-terminal oligopyrimidine tract. Here we show that LiCl can
      alleviate the translational repression of these mRNAs when progression through
      the cell cycle is blocked at G(0), G(1)/S, or G(2)/M phases in different cell
      lines and by various physiological and chemical means. This derepressive effect
      of LiCl does not involve resumption of cell division. Unlike its efficient
      derepressive effect in mitotically arrested cells, LiCl alleviates inefficiently
      the repression of TOP mRNAs in amino acid-deprived cells and has no effect in
      lymphoblastoids whose TOP mRNAs are constitutively repressed even when they are
      proliferating. LiCl is widely used as a relatively selective inhibitor of
      glycogen synthase kinase-3. However, inhibition per se of this enzyme by more
      specific drugs failed to derepress the translation of TOP mRNAs, implying that
      relief of the translational repression of TOP mRNAs by LiCl is carried out in a
      glycogen synthase kinase-3-independent manner. Moreover, this effect is apparent,
      at least in some cell lines, in the absence of S6-kinase 1 activation and
      ribosomal protein S6 phosphorylation, thus further supporting the notion that
      translational control of TOP mRNAs does not rely on either of these variables.

PMID- 15569666
TI  - A role for SlyD in the Escherichia coli hydrogenase biosynthetic pathway.
AB  - The [NiFe] centers at the active sites of the Escherichia coli hydrogenase
      enzymes are assembled by a team of accessory proteins that includes the products
      of the hyp genes. To determine whether any other proteins are involved in this
      process, the sequential peptide affinity system was used. The analysis of the
      proteins in a complex with HypB revealed the peptidyl-prolyl cis/trans-isomerase
      SlyD, a metal-binding protein that has not been previously linked to the
      hydrogenase biosynthetic pathway. The association between HypB and SlyD was
      confirmed by chemical cross-linking of purified proteins. Deletion of the slyD
      gene resulted in a marked reduction of the hydrogenase activity in cell extracts
      prepared from anaerobic cultures, and an in-gel assay was used to demonstrate
      diminished activities of both hydrogenase 1 and 2. Western analysis revealed a
      decrease in the final proteolytic processing of the hydrogenase 3 HycE protein,
      indicating that the metal center was not assembled properly. These deficiencies
      were all rescued by growth in medium containing excess nickel, but zinc did not
      have any phenotypic effect. Experiments with radioactive nickel demonstrated that
      less nickel accumulated in DeltaslyD cells compared with wild type, and
      overexpression of SlyD from an inducible promoter doubled the level of cellular
      nickel. These experiments demonstrate that SlyD has a role in the nickel
      insertion step of the hydrogenase maturation pathway, and the possible functions
      of SlyD are discussed.

PMID- 15569667
TI  - Peroxisome proliferator-activated receptor gamma agonists promote TRAIL-induced
      apoptosis by reducing survivin levels via cyclin D3 repression and cell cycle
      arrest.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      cancer therapy that preferentially induces apoptosis in cancer cells. However,
      many neoplasms are resistant to TRAIL by mechanisms that are poorly understood.
      Here we demonstrate that human breast cancer cells, but not normal mammary
      epithelial cells, are dramatically sensitized to TRAIL-induced apoptosis and
      caspase activation by peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists of the thiazolidinedione (TZD) class. Although TZDs do not
      significantly alter the expression of components of the TRAIL signaling pathway,
      they profoundly reduce protein levels of cyclin D3, but not other D-type cyclins,
      by decreasing cyclin D3 mRNA levels and by inducing its proteasomal degradation.
      Importantly, both TRAIL sensitization and reduction in cyclin D3 protein levels
      induced by TZDs are likely PPARgamma-independent because a dominant negative
      mutant of PPARgamma did not antagonize these effects of TZDs, nor were they
      affected by the expression levels of PPARgamma. TZDs also inhibit G(1) to S cell
      cycle progression. Furthermore, silencing cyclin D3 by RNA interference inhibits
      S phase entry and sensitizes breast cancer cells to TRAIL, indicating a key role
      for cyclin D3 repression in these events. G(1) cell cycle arrest sensitizes
      breast cancer cells to TRAIL at least in part by reducing levels of the anti
      apoptotic protein survivin: ectopic expression of survivin partially suppresses
      apoptosis induced by TRAIL and TZDs. We also demonstrate for the first time that
      TZDs promote TRAIL-induced apoptosis of breast cancer in vivo, suggesting that
      this combination may be an effective therapy for cancer.

PMID- 15569668
TI  - Extracellular pH modifies mitochondrial control of capacitative calcium entry in
      Jurkat cells.
AB  - It was found that a collapse of the mitochondrial calcium buffering caused by the
      protonophoric uncoupler CCCP, antimycin A plus oligomycin, or the inhibitor of
      the mitochondrial Ca2+/Na+ exchanger led to a strong inhibition of thapsigargin
      induced capacitative Ca2+ entry (CCE) into Jurkat cells suspended in a medium at
      pH 7.2. The effect of these inhibitors was markedly less significant at higher
      extracellular pH. Moreover, dysfunction of the mitochondrial calcium handling
      greatly decreased CCE sensitivity to extracellular Ca2+ when the pH of
      extracellular solution was 7.2 (apparent Kd toward extracellular Ca2+ rose from
      2.3 +/- 0.6 mm in control cells to 11.0 +/- 1.7 mM in CCCP-treated cells) as
      compared with pH 7.8 (apparent Kd toward extracellular Ca2+ increased from 1.3 +/
      0.4 mM in control cells to 2.4 +/- 0.4 mM in uncoupler-treated cells). Changes
      in intracellular pH triggered by methylamine did not influence Ca2+ influx. This
      suggests that, in Jurkat cells, store-operated calcium channels sense
      extracellular pH change as a parameter that modifies their sensitivity to
      intracellular Ca2+. In contrast, in human osteosarcoma cells, changes in
      extracellular pH as well as mitochondrial uncoupling did not exert any inhibitory
      effects on CCE.

PMID- 15569669
TI  - Molecular ordering of the caspase activation cascade initiated by the cytotoxic T
      lymphocyte/natural killer (CTL/NK) protease granzyme B.
AB  - Granzyme B is a major cytotoxic T lymphocyte/natural killer (CTL/NK) granule
      protease that can activate members of the caspase family of cysteine proteases
      through processing of caspase zymogens. However, the molecular order and relative
      importance of caspase activation events that occur in target cells during
      granzyme B-initiated apoptosis has not been established. Here, we have examined
      the hierarchy of granzyme B-initiated caspase activation events using a cell-free
      system where all caspases are present at physiological levels. We show that
      granzyme B initiates a two-tiered caspase activation cascade involving seven
      caspases, where caspase-3 is required for the second tier of caspase activation
      events. Using a two-dimensional gel-based proteomics approach we have also
      examined the scale of granzyme B-initiated alterations to the proteome in the
      presence or absence of effector caspase-3 or -7. These studies indicate that
      granzyme B targets a highly restricted range of substrates and orchestrates
      cellular demolition largely through activation of caspase-3.

PMID- 15569670
TI  - Global effects of BCR/ABL and TEL/PDGFRbeta expression on the proteome and
      phosphoproteome: identification of the Rho pathway as a target of BCR/ABL.
AB  - Many leukemic oncogenes form as a consequence of gene fusions or mutation that
      result in the activation or overexpression of a tyrosine kinase. To identify
      commonalities and differences in the action of two such kinases, breakpoint
      cluster region (BCR)/ABL and TEL/PDGFRbeta, two-dimensional gel electrophoresis
      was employed to characterize their effects on the proteome. While both oncogenes
      affected expression of specific proteins, few common effects were observed. A
      number of proteins whose expression is altered by BCR/ABL, including gelsolin and
      stathmin, are related to cytoskeletal function whereas no such changes were seen
      in TEL/PDGFRbeta-transfected cells. Treatment of cells with the kinase inhibitor
      STI571 for 4-h reversed changes in expression of some of these cytoskeletal
      proteins. Correspondingly, BCR/ABL-transfected cells were less responsive to
      chemotactic and chemokinetic stimuli than non-transfected cells and TEL/PDGFRbeta
      transfected Ba/F3 cells. Decreased motile response was reversed by a 16-h
      treatment with STI571. A phosphoprotein-specific gel stain was used to identify
      TEL/PDGFRbeta and BCR/ABL-mediated changes in the phosphoproteome. These included
      changes on Crkl, Ras-GAP-binding protein 1, and for BCR/ABL, cytoskeletal
      proteins such as tubulin, and Nedd5. Decreased phosphorylation of Rho-GTPase
      dissociation inhibitor (Rho GDI) was also observed in BCR/ABL-transfected cells.
      This results in the activation of the Rho pathway, and treatment of cells with
      Y27632, an inhibitor of Rho kinase, inhibited DNA synthesis in BCR/ABL
      transfected Ba/F3 cells but not TEL/PDGFRbeta-expressing cells. Expression of a
      dominant-negative RhoA inhibited both DNA synthesis and transwell migration,
      demonstrating the significance of this pathway in BCR/ABL-mediated
      transformation.

PMID- 15569671
TI  - Hydrogen peroxide potentiates volume-sensitive excitatory amino acid release via
      a mechanism involving Ca2+/calmodulin-dependent protein kinase II.
AB  - Excessive excitatory amino acid (EAA) release in cerebral ischemia is a major
      mechanism responsible for neuronal damage and death. A substantial fraction of
      ischemic EAA release occurs via volume-regulated anion channels (VRACs). Hydrogen
      peroxide (H2O2), which is abundantly produced during ischemia and reperfusion,
      activates a number of protein kinases critical for VRAC functioning and has
      recently been reported to activate VRACs. In the present study, we explored the
      effects of H2O2 on volume-dependent EAA release in cultured astrocytes, measured
      as the release of preloaded D-[3H]aspartate. 100-1,000 microm H2O2 enhanced
      swelling-induced EAA release by approximately 2.5-3-fold (EC50 approximately 10
      microM). The VRAC blockers ATP, phloretin, and 5-nitro-2-(3-phenylpropylamino)
      benzoate (NPPB) potently inhibited both control swelling-induced and the H2O2
      potentiated release, suggesting a role for VRACs. The H2O2-induced component of
      EAA release was attenuated by the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) and completely
      eliminated by the calmodulin antagonists trifluoperazine and W-7 and the
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93. Inhibitors
      of tyrosine kinases, protein kinase C, and the myosin light chain kinase were
      ineffective in blocking the H2O2 response. H2O2 treatment of swollen astrocytes,
      but not swelling alone, resulted in CaMKII activation that was inhibited by KN
      93, as determined by a phospho-Thr286 CaMKII antibody. These data demonstrate
      that H2O2 strongly up-regulates astrocytic volume-sensitive EAA release via a
      CaMKII-dependent mechanism and in this way may potently promote pathological EAA
      release and brain damage in ischemia.

PMID- 15569672
TI  - Protein phosphatase 2A regulates apoptosis in neutrophils by dephosphorylating
      both p38 MAPK and its substrate caspase 3.
AB  - The induction of apoptosis in neutrophils is an essential event in the resolution
      of an inflammatory process. We found recently that the reduction of the activity
      of the neutrophil survival factor p38 MAPK and dephosphorylation and thus
      activation of caspases must occur to initiate such cell death in these
      leukocytes. Here, we report a previously undetected early and transient
      activation of protein phosphatase 2A (PP2A) in neutrophils undergoing apoptosis.
      The pharmacological inhibition of this phosphatase during Fas-induced apoptosis
      augmented the levels of phosphorylation of both p38 MAPK and caspase 3, resulting
      in a decreased activity of caspase 3 and an increased neutrophil survival. The
      complementary finding of a time-dependent association among PP2A, p38 MAPK, and
      caspase 3 in intact neutrophils indicated that there is a direct regulatory link
      among these signaling enzymes during Fas-provoked apoptosis. Moreover,
      immunoprecipitated active p38 MAPK and recombinant phosphorylated caspase 3 were
      dephosphorylated by exposure to purified PP2A in vitro. Consequently, the early
      and temporary activation of PP2A in neutrophils impaired not only the p38 MAPK
      mediated inhibition of caspase 3 but also restored the activity to caspase 3 that
      had already been phosphorylated and thereby inactivated. These findings indicate
      that PP2A plays a pivotal dual role in the induction of neutrophil apoptosis and
      therefore also in the resolution of inflammation.

PMID- 15569673
TI  - Local activation of Rap1 contributes to directional vascular endothelial cell
      migration accompanied by extension of microtubules on which RAPL, a Rap1
      associating molecule, localizes.
AB  - Endothelial cell migration is promoted by chemoattractants and is accompanied
      with microtubule extension toward the leading edge. Cytoskeletal microtubules
      polarize to function as rails for delivering a variety of molecules by motor
      proteins during cell migration. It remains, however, unclear how directional
      migration with polarized extension of microtubules is regulated. Here we report
      that Rap1 controls the migration of vascular endothelial cells. We found that
      Rap1-associating molecule, RAPL, which belongs to the Ras association domain
      family (Rassf), localized on microtubules and that activated Rap1 induced
      dissociation of RAPL from microtubules. A Rap1 activation-monitoring probe based
      on the fluorescence resonance energy transfer enabled us to demonstrate that
      local Rap1 activation occurs at the leading edge of the cells under the two types
      of cell migration, chemotaxis and wound healing. Time lapse imaging of
      microtubules marked by enhanced green fluorescent protein-RAPL showed the
      directional growth of microtubules toward the leading edge of the migrating
      cells. Using adenovirus, inactivation of Rap1 by expression of rap1GAPII
      inhibited wound healing. In addition, disconnection of Rap1 and RAPL by
      expression of a RAPL mutant also perturbed wound healing. Collectively, the
      locally activated Rap1 and its association with RAPL controls the directional
      migration of vascular endothelial cells.

PMID- 15569674
TI  - Gamma-secretase exists on the plasma membrane as an intact complex that accepts
      substrates and effects intramembrane cleavage.
AB  - Research on Alzheimer's disease led to the identification of a novel proteolytic
      mechanism in all metazoans, the presenilin/gamma-secretase complex. This unique
      intramembrane-cleaving aspartyl protease is required for the normal processing of
      Notch, Jagged, beta-amyloid precursor protein (APP), E-cadherin, and many other
      receptor-like proteins. We recently provided indirect evidence of gamma-secretase
      activity at the cell surface in HeLa cells following inhibition of receptor
      mediated endocytosis. Here, we directly identify and isolate gamma-secretase as
      an intact complex (Presenilin, Nicastrin, Aph-1, and Pen-2) from the plasma
      membrane, both in overexpressing cell lines and endogenously. Inhibition of its
      proteolytic activity allowed cell surface gamma-secretase to be captured in
      association with its plasma membrane-localized APP substrates (C83 and C99).
      Moreover, non-denaturing isolation of the intact enzyme complex revealed that
      cell surface gamma-secretase can specifically generate amyloid beta-protein from
      an APP substrate and similarly cleave a Notch substrate. These data directly
      establish the proteolytic function of gamma-secretase on the plasma membrane,
      independent of a hypothesized substrate trafficking role. We conclude that
      presenilin/gamma-secretase exists as a mature complex at the cell surface, where
      it interacts with and can cleave its substrates, consistent with an essential
      function in processing many adhesion molecules and receptors required for cell
      cell interaction or intercellular signaling.

PMID- 15569675
TI  - Homotypic fibrillin-1 interactions in microfibril assembly.
AB  - We have defined the homotypic interactions of fibrillin-1 to obtain new insights
      into microfibril assembly. Dose-dependent saturable high affinity binding was
      demonstrated between N-terminal fragments, between furin processed C-terminal
      fragments, and between these N- and C-terminal fragments. The N terminus also
      interacted with a downstream fragment. A post-furin cleavage site C-terminal
      sequence also interacted with the N terminus, with itself and with the furin
      processed fragment. No other homotypic fibrillin-1 interactions were detected.
      Some terminal homotypic interactions were inhibited by other terminal sequences,
      and were strongly calcium-dependent. Treatment of an N-terminal fragment with N
      ethylmaleimide reduced homotypic binding. Microfibril-associated glycoprotein-1
      inhibited N- to C-terminal interactions but not homotypic N-terminal
      interactions. These fibrillin-1 interactions are likely to regulate pericellular
      fibrillin-1 microfibril assembly.

PMID- 15569676
TI  - The BRCA1 RING and BRCT domains cooperate in targeting BRCA1 to ionizing
      radiation-induced nuclear foci.
AB  - BRCA1 accumulates in nuclear foci during S-phase and reassembles into DNA repair
      associated foci after DNA damage, reflecting its role in genome maintenance.
      BRCA1 comprises a RING domain at the N terminus and a BRCT domain at the C
      terminus, through which it associates with DNA repair proteins. The key sequences
      that target BRCA1 to DNA damage-induced foci have not been identified. Here, we
      mapped the BRCA1 foci-targeting domains of yellow fluorescence protein (YFP)
      tagged BRCA1 in MCF-7 breast cancer cells exposed to ionizing radiation (IR).
      Cancer mutations specific to the BRCT domain, but not the RING domain, abolished
      BRCA1 recruitment to IR-induced foci. The YFP-BRCT domain itself, however,
      localized poorly at IR-induced foci, and the RING domain and other sequences were
      negative. We discovered that only when the RING and BRCT domains were combined
      was foci targeting restored to levels observed for wild-type BRCA1. The RING-BRCT
      fusion co-localized at foci with the MDC1 DNA damage response factor and
      inhibited entry of endogenous BRCA1 into nuclear foci. Our results explain why
      exon 11-deficient BRCA1 splice variants are targeted to IR-induced foci even
      though they are incapable of repairing DNA damage. We propose that both RING and
      BRCT domains together target BRCA1 to large focal assemblies at DNA double
      stranded breaks.

PMID- 15569677
TI  - Bone marrow stromal cell-derived growth inhibitor inhibits growth and migration
      of breast cancer cells via induction of cell cycle arrest and apoptosis.
AB  - Genes encoding growth-inhibitory proteins are postulated to be candidate tumor
      suppressors. The identification of such proteins may benefit the early diagnosis
      and therapy of tumors. Here we report the cloning and functional characterization
      of a novel human bone marrow stromal cell (BMSC)-derived growth inhibitor (BDGI)
      by large scale random sequencing of a human BMSC cDNA library. Human BDGI cDNA
      encodes a 477-amino acid residue protein that shares high homology with rat and
      mouse pregnancy-induced growth inhibitors. The C-terminal of BDGI is identical to
      a novel human pregnancy-induced growth inhibitor, OKL38. BDGI is also closely
      related to many other eukaryotic proteins, which together form a novel and highly
      conserved family of BDGI-like proteins. BDGI overexpression inhibits the
      proliferation, decreases anchorage-dependent growth, and reduces migration of MCF
      7 human breast cancer cells, whereas down-regulation of BDGI expression promotes
      the proliferation of MCF-7 and HeLa cervix epitheloid carcinoma cells.
      Interestingly, the inhibitory effect of BDGI on MCF-7 cells is more potent than
      that of OKL38. We demonstrate that BDGI induces cell cycle arrest in S phase and
      subsequent apoptosis of MCF-7 cells, which is likely to account for the
      antiproliferative effects of BDGI. This process may involve up-regulation of
      p27Kip1 and down-regulation of cyclin A, Bcl-2, and Bcl-xL. The inhibitory effect
      of BDGI on cell proliferation and the induction of apoptosis were also observed
      in A549 lung cancer cells but not HeLa cells. These results indicate that BDGI
      might be a growth inhibitor for human tumor cells, especially breast cancer
      cells, possibly contributing to the development of new therapeutic strategies for
      breast cancer.

PMID- 15569678
TI  - Modulation of secretory granule-targeting efficiency by cis and trans compounding
      of sorting signals.
AB  - Several protein domains acting through seemingly different mechanisms have been
      reported to have the capacity to target proteins to dense core secretory
      granules. Because proteins enter secretory granules with different efficiencies
      and because some of these proteins contain more than one granule-targeting motif,
      we have investigated whether compounding sorting signals could alter the
      efficiency of protein entry into secretory granules. In the current study we
      demonstrate that a paired basic cleavage site from human prorenin and an alpha
      helix-containing secretory granule-sorting signal from the prohormone convertase
      PC1/3 can synergize to increase granule-sorting efficiency not only when located
      on the same protein, but also when located on distinct proteins that associate in
      the secretory pathway.

PMID- 15569679
TI  - Common features in the functional surface of scorpion beta-toxins and elements
      that confer specificity for insect and mammalian voltage-gated sodium channels.
AB  - Scorpion beta-toxins that affect the activation of mammalian voltage-gated sodium
      channels (Navs) have been studied extensively, but little is known about their
      functional surface and mode of interaction with the channel receptor. To enable a
      molecular approach to this question, we have established a successful expression
      system for the anti-mammalian scorpion beta-toxin, Css4, whose effects on rat
      brain Navs have been well characterized. A recombinant toxin, His-Css4, was
      obtained when fused to a His tag and a thrombin cleavage site and had similar
      binding affinity for and effect on Na currents of rat brain sodium channels as
      those of the native toxin isolated from the scorpion venom. Molecular dissection
      of His-Css4 elucidated a functional surface of 1245 A2 composed of the following:
      1) a cluster of residues associated with the alpha-helix, which includes a
      putative "hot spot" (this cluster is conserved among scorpion beta-toxins and
      contains their "pharmacophore"); 2) a hydrophobic cluster associated mainly with
      the beta2 and beta3 strands, which is likely to confer the specificity for
      mammalian Navs; 3) a single bioactive residue (Trp-58) in the C-tail; and 4) a
      negatively charged residue (Glu-15) involved in voltage sensor trapping as
      inferred from our ability to uncouple toxin binding from activity upon its
      substitution. This study expands our understanding about the mode of action of
      scorpion beta-toxins and illuminates differences in the functional surfaces that
      may dictate their specificities for mammalian versus insect sodium channels.

PMID- 15569680
TI  - alpha-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced
      apoptosis and DNA damage.
AB  - Ultraviolet radiation is a well established epidemiologic risk factor for
      malignant melanoma. This observation has been linked to the relative resistance
      of normal melanocytes to ultraviolet B (UVB) radiation-induced apoptosis, which
      consequently leads to accumulation of UVB radiation-induced DNA lesions in
      melanocytes. Therefore, identification of physiologic factors regulating UVB
      radiation-induced apoptosis and DNA damage of melanocytes is of utmost biological
      importance. We show that the neuropeptide alpha-melanocyte-stimulating hormone
      (alpha-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in
      vitro. The anti-apoptotic activity of alpha-MSH is not mediated by filtering or
      by induction of melanin synthesis in melanocytes. alpha-MSH neither leads to
      changes in the cell cycle distribution nor induces alterations in the expression
      of the apoptosis-related proteins Bcl(2), Bcl(x), Bax, p53, CD95 (Fas/APO-1), and
      CD95L (FasL). In contrast, alpha-MSH markedly reduces the formation of UVB
      radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane
      pyrimidine dimers, ultimately leading to reduced apoptosis. The reduction of UV
      radiation-induced DNA damage by alpha-MSH appears to be related to induction of
      nucleotide excision repair, because UV radiation-mediated apoptosis was not
      blocked by alpha-MSH in nucleotide excision repair-deficient fibroblasts. These
      data, for the first time, demonstrate regulation of UVB radiation-induced
      apoptosis of human melanocytes by a neuropeptide that is physiologically
      expressed within the epidermis. Apart from its ability to induce photoprotective
      melanin synthesis, alpha-MSH appears to exert the capacity to reduce UV radiation
      induced DNA damage and, thus, may act as a potent protection factor against the
      harmful effects of UV radiation on the genomic stability of epidermal cells.

PMID- 15569681
TI  - Nef-induced alteration of the early/recycling endosomal compartment correlates
      with enhancement of HIV-1 infectivity.
AB  - human immunodeficiency virus type 1 (HIV-1) Nef interacts with the clathrin
      associated AP-1 and AP-3 adaptor complexes, stabilizing their association with
      endosomal membranes. These findings led us to hypothesize a general impact of
      this viral protein on the endosomal system. Here, we have shown that Nef
      specifically disturbs the morphology of the early/recycling compartment, inducing
      a redistribution of early endosomal markers and a shortening of the tubular
      recycling endosomal structures. Furthermore, Nef modulates the trafficking of the
      transferrin receptor (TfR), the prototypical recycling surface protein,
      indicating that it also disturbs the function of this compartment. Nef reduces
      the rate of recycling of TfR to the plasma membrane, causing TfR to accumulate in
      early endosomes and reducing its expression at the cell surface. These effects
      depend on the leucine-based motif of Nef, which is required for the membrane
      stabilization of AP-1 and AP-3 complexes. Since we show that this motif is also
      required for the full infectivity of HIV-1 virions, these results indicate that
      the positive influence of Nef on viral infectivity may be related to its general
      effects on early/recycling endosomal compartments.

PMID- 15569682
TI  - Direct interaction of a divergent CaM isoform and the transcription factor, MYB2,
      enhances salt tolerance in arabidopsis.
AB  - Calmodulin (CaM), a ubiquitous calcium-binding protein, regulates diverse
      cellular functions by modulating the activity of a variety of enzymes and
      proteins. Plants express numerous CaM isoforms that exhibit differential
      activation and/or inhibition of CaM-dependent enzymes in vitro. However, the
      specific biological functions of plant CaM are not well known. In this study, we
      isolated a cDNA encoding a CaM binding transcription factor, MYB2, that regulates
      the expression of salt- and dehydration-responsive genes in Arabidopsis. This was
      achieved using a salt-inducible CaM isoform (GmCaM4) as a probe from a salt
      treated Arabidopsis expression library. Using domain mapping, we identified a
      Ca2+-dependent CaM binding domain in MYB2. The specific binding of CaM to CaM
      binding domain was confirmed by site-directed mutagenesis, a gel mobility shift
      assay, split ubiquitin assay, and a competition assay using a Ca2+/CaM-dependent
      enzyme. Interestingly, the specific CaM isoform GmCaM4 enhances the DNA binding
      activity of AtMYB2, whereas this was inhibited by a closely related CaM isoform
      (GmCaM1). Overexpression of Gm-CaM4 in Arabidopsis up-regulates the transcription
      rate of AtMYB2-regulated genes, including the proline-synthesizing enzyme P5CS1
      (Delta1-pyrroline-5-carboxylate synthetase-1), which confers salt tolerance by
      facilitating proline accumulation. Therefore, we suggest that a specific CaM
      isoform mediates salt-induced Ca2+ signaling through the activation of an MYB
      transcriptional activator, thereby resulting in salt tolerance in plants.

PMID- 15569683
TI  - Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required
      for its SUMO-1 modification and colocalization with the promyelocytic leukemia
      protein.
AB  - SUMO-1 is a member of a family of ubiquitin-like molecules that are post
      translationally conjugated to various cellular proteins in a process that is
      mechanistically similar to ubiquitylation. To identify molecules that bind
      noncovalently to SUMO-1, we performed yeast two-hybrid screening with a SUMO-1
      mutant that cannot be conjugated to target proteins as the bait. This screening
      resulted in the isolation of cDNAs encoding the b isoform of thymine DNA
      glycosylase (TDGb). A deletion mutant of TDGb (TDGb(Delta11)) that lacks a region
      shown to be required for noncovalent binding of SUMO-1 was also found not to be
      susceptible to SUMO-1 conjugation at an adjacent lysine residue, suggesting that
      such binding is required for covalent modification. In contrast, another mutant
      of TDGb (TDGb(KR)) in which the lysine residue targeted for SUMO-1 conjugation is
      replaced with arginine retained the ability to bind SUMO-1 non-covalently. TDGb
      was shown to interact with the promyelocytic leukemia protein (PML) in vitro as
      well as to colocalize with this protein to nuclear bodies in transfected cells.
      TDGb(KR) also colocalized with PML, whereas TDGb(Delta11) did not, indicating
      that the noncovalent SUMO-1 binding activity of TDGb is required for
      colocalization with PML. Furthermore, SUMO-1 modification of TDGb and PML
      enhanced the interaction between the two proteins. These results suggest that
      SUMO-1 functions to tether proteins to PML-containing nuclear bodies through post
      translational modification and noncovalent protein-protein interaction.

PMID- 15569684
TI  - Extracellular signal-regulated kinases 1/2 control claudin-2 expression in Madin
      Darby canine kidney strain I and II cells.
AB  - The tight junction of the epithelial cell determines the characteristics of
      paracellular permeability across epithelium. Recent work points toward the
      claudin family of tight junction proteins as leading candidates for the molecular
      components that regulate paracellular permeability properties in epithelial
      tissues. Madin-Darby canine kidney (MDCK) strain I and II cells are models for
      the study of tight junctions and based on transepithelial electrical resistance
      (TER) contain "tight" and "leaky" tight junctions, respectively. Overexpression
      studies suggest that tight junction leakiness in these two strains of MDCK cells
      is conferred by expression of the tight junction protein claudin-2. Extracellular
      signal-regulated kinase (ERK) 1/2 activation by hepatocyte growth factor
      treatment of MDCK strain II cells inhibited claudin-2 expression and transiently
      increased TER. This process was blocked by the ERK 1/2 inhibitor U0126.
      Transfection of constitutively active mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase into MDCK strain II cells
      also inhibited claudin-2 expression and increased TER. MDCK strain I cells have
      higher levels of active ERK 1/2 than do MDCK strain II cells. U0126 treatment of
      MDCK strain I cells decreased active ERK 1/2 levels, induced expression of
      claudin-2 protein, and decreased TER by approximately 20-fold. U0126 treatment
      also induced claudin-2 expression and decreased TER in a high resistance mouse
      cortical collecting duct cell line (94D). These data show for the first time that
      the ERK 1/2 signaling pathway negatively controls claudin-2 expression in
      mammalian renal epithelial cells and provide evidence for regulation of tight
      junction paracellular transport by alterations in claudin composition within
      tight junction complexes.

PMID- 15569685
TI  - Structural and dynamics studies of the D54A mutant of human T cell leukemia virus
      1 capsid protein.
AB  - The human T cell leukemia virus and the human immunodeficiency virus share a
      highly conserved, predominantly helical two-domain mature capsid (CA) protein
      structure with an N-terminal beta-hairpin. Despite overall structural similarity,
      differences exist in the backbone dynamic properties of the CA N-terminal domain.
      Since studies with other retroviruses suggest that the beta-hairpin is critical
      for formation of a CA-CA interface, we investigated the functional role of the
      human T cell leukemia virus beta-hairpin by disrupting the salt bridge between
      Pro(1) and Asp(54) that stabilizes the beta-hairpin. NMR (15)N relaxation data
      were used to characterize the backbone dynamics of the D54A mutant in the context
      of the N-terminal domains, compared with the wild-type counterpart. Moreover, the
      effect of the mutation on proteolytic processing and release of virus-like
      particles (VLPs) from human cells in culture was determined. Conformational and
      dynamic changes resulting from the mutation were detected by NMR spectroscopy.
      The mutation also altered the conformation of mature CA in cells and VLPs, as
      reflected by differential antibody recognition of the wild-type and mutated CA
      proteins. In contrast, the mutation did not detectably affect antibody
      recognition of the CA protein precursor or release of VLPs assembled by the
      precursor, consistent with the fact that the hairpin cannot form in the precursor
      molecule. The particle morphology and size were not detectably affected. The
      results indicate that the beta-hairpin contributes to the overall structure of
      the mature CA protein and suggest that differences in the backbone dynamics of
      the beta-hairpin contribute to mature CA structure, possibly introducing
      flexibility into interface formation during proteolytic maturation.

PMID- 15569686
TI  - Heart-directed expression of a human cardiac isoform of cAMP-response element
      modulator in transgenic mice.
AB  - The transcriptional activation mediated by cAMP-response element (CRE) and
      transcription factors of the CRE-binding protein (CREB)/CRE modulator (CREM)
      family represents an important mechanism of cAMP-dependent gene regulation
      possibly implicated in detrimental effects of chronic beta-adrenergic stimulation
      in end-stage heart failure. We studied the cardiac role of CREM in transgenic
      mice with heart-directed expression of CREM-IbDeltaC-X, a human cardiac CREM
      isoform. Transgenic mice displayed atrial enlargement with atrial and ventricular
      hypertrophy, developed atrial fibrillation, and died prematurely. In vivo
      hemodynamic assessment revealed increased contractility of transgenic left
      ventricles probably due to a selective up-regulation of SERCA2, the cardiac
      Ca(2+)-ATPase of the sarcoplasmic reticulum. In transgenic ventricles, reduced
      phosphorylation of phospholamban and of the CREB was associated with increased
      activity of serine-threonine protein phosphatase 1. The density of beta(1)
      adrenoreceptor was increased, and messenger RNAs encoding transcription factor
      dHAND and small G-protein RhoB were decreased in transgenic hearts as compared
      with wild-type controls. Our results indicate that heart-directed expression of
      CREM-IbDeltaC-X leads to complex cardiac alterations, suggesting CREM as a
      central regulator of cardiac morphology, function, and gene expression.

PMID- 15569687
TI  - Ca2+/calmodulin kinase-dependent activation of hypoxia inducible factor 1
      transcriptional activity in cells subjected to intermittent hypoxia.
AB  - Intermittent hypoxia (IH) occurs in many pathological conditions. However, very
      little is known about the molecular mechanisms associated with IH. Hypoxia
      inducible factor 1 (HIF-1) mediates transcriptional responses to continuous
      hypoxia. In the present study, we investigated whether IH activates HIF-1 and, if
      so, which signaling pathways are involved. PC12 cells were exposed to either to
      20% O2 (non-hypoxic control) or to 60 cycles consisting of 30 s at 1.5% O2,
      followed by 4 min at 20% O2 (IH). Western blot analysis revealed significant
      increases in HIF-1alpha protein in nuclear extracts of cells subjected to IH.
      Expression of a HIF-1-dependent reporter gene was increased 3-fold in cells
      subjected to IH. Although IH induced the activation of ERK1, ERK2, JNK, PKC
      alpha, and PKC-gamma, inhibitors of these kinases and of phosphatidylinositol 3
      kinase did not block HIF-1-mediated reporter gene expression induced by IH,
      indicating that signaling via these kinases was not required. In contrast,
      addition of the intracellular Ca2+ chelator BAPTA-AM or the Ca2+/calmodulin
      dependent (CaM) kinase inhibitor KN93 blocked reporter gene activation in
      response to IH. CaM kinase activity was increased 5-fold in cells subjected to
      IH. KN 93 prevented IH-induced transactivation mediated by HIF-1alpha, and its
      coactivator p300, which was phosphorylated by CaM kinase II in vitro. Expression
      of the HIF-1-regulated gene encoding tyrosine hydroxylase was induced by IH and
      this effect was blocked by KN93. These observations suggest that IH induces HIF-1
      transcriptional activity via a novel signaling pathway involving CaM kinase.

PMID- 15569688
TI  - The adaptor protein HSH2 attenuates apoptosis in response to ligation of the B
      cell antigen receptor complex on the B lymphoma cell line, WEHI-231.
AB  - Signals transduced by the B cell antigen receptor (BCR) play a central role in
      regulating the functional response of the cell to antigen. Depending on the
      nature of the antigenic signal and the developmental or differentiation state of
      the B cell, antigen receptor signaling can promote either apoptosis or survival
      and activation. Understanding the molecular mechanisms underlying BCR-mediated
      apoptosis constitutes an important area of research because aberrations in
      programmed cell death can result in the development of autoimmunity or cancer.
      Expression of the adaptor protein hematopoietic Src homology 2 (HSH2) was found
      to significantly decrease BCR-mediated apoptosis in the murine WEHI-231 cell
      line. Analysis of signal transduction pathways activated in response to BCR
      ligation revealed that HSH2 does not significantly alter total protein tyrosine
      phosphorylation or Ca2+ mobilization. HSH2 does not potentiate the activation
      dependent phosphorylation of AKT either. With respect to MAPK activation, HSH2
      was not observed to alter the activation of ERK or p38 in response to BCR
      ligation, but it does significantly potentiate JNK activation. Analysis of
      processes directly associated with apoptosis revealed that HSH2 inhibits
      mitochondrial depolarization to a significant degree, whereas it has only a
      slight effect on caspase activation and poly ADP-ribose polymerase cleavage. BCR
      induced apoptosis of WEHI-231 cells is associated with the loss of endogenous
      HSH2 expression within 12 h, whereas inhibition of apoptosis in response to CD40
      mediated signaling leads to stabilization of HSH2 expression. Thus, endogenous
      HSH2 expression correlates directly with survival of WEHI-231 cells, which
      supports the hypothesis that HSH2 modulates the apoptotic response through its
      ability to directly or indirectly promote mitochondrial stability.

PMID- 15569689
TI  - Impaired Ca2+ store functions in skeletal and cardiac muscle cells from
      sarcalumenin-deficient mice.
AB  - Sarcalumenin (SAR), specifically expressed in striated muscle cells, is a Ca2+
      binding protein localized in the sarcoplasmic reticulum (SR) of the intracellular
      Ca2+ store. By generating SAR-deficient mice, we herein examined its
      physiological role. The mutant mice were apparently normal in growth, health, and
      reproduction, indicating that SAR is not essential for fundamental muscle
      functions. SAR-deficient skeletal muscle carrying irregular SR ultrastructures
      retained normal force generation but showed slow relaxation phases after
      contractions. A weakened Ca2+ uptake activity was detected in the SR prepared
      from mutant muscle, indicating that SAR contributes to Ca2+ buffering in the SR
      lumen and also to the maintenance of Ca2+ pump proteins. Cardiac myocytes from
      SAR-deficient mice showed slow contraction and relaxation accompanied by impaired
      Ca2+ transients, and the mutant mice exhibited a number of impairments in cardiac
      performance as determined in electrocardiography, ventricular catheterization,
      and echocardiography. The results obtained demonstrate that SAR plays important
      roles in improving the Ca2+ handling functions of the SR in striated muscle.

PMID- 15569690
TI  - Functional cross-talk between fatty acid synthesis and nonribosomal peptide
      synthesis in quinoxaline antibiotic-producing streptomycetes.
AB  - Quinoxaline antibiotics are chromopeptide lactones embracing the two families of
      triostins and quinomycins, each having characteristic sulfur-containing cross
      bridges. Interest in these compounds stems from their antineoplastic activities
      and their specific binding to DNA via bifunctional intercalation of the twin
      chromophores represented by quinoxaline-2-carboxylic acid (QA). Enzymatic
      analysis of triostin A-producing Streptomyces triostinicus and quinomycin A
      producing Streptomyces echinatus revealed four nonribosomal peptide synthetase
      modules for the assembly of the quinoxalinoyl tetrapeptide backbone of the
      quinoxaline antibiotics. The modules were contained in three protein fractions,
      referred to as triostin synthetases (TrsII, III, and IV). TrsII is a 245-kDa
      bimodular nonribosomal peptide synthetase activating as thioesters for both
      serine and alanine, the first two amino acids of the quinoxalinoyl tetrapeptide
      chain. TrsIII, represented by a protein of 250 kDa, activates cysteine as a
      thioester. TrsIV, an unstable protein of apparent Mr about 280,000, was
      identified by its ability to activate and N-methylate valine, the last amino
      acid. QA, the chromophore, was shown to be recruited by a free-standing
      adenylation domain, TrsI, in conjunction with a QA-binding protein, AcpPSE.
      Cloning of the gene for the QA-binding protein revealed that it is the fatty acyl
      carrier protein, AcpPSE, of the fatty acid synthase of S. echinatus and S.
      triostinicus. Analysis of the acylation reaction of AcpPSE by TrsI along with
      other A-domains and the aroyl carrier protein AcmACP from actinomycin
      biosynthesis revealed a specific requirement for AcpPSE in the activation and
      also in the condensation of QA with serine in the initiation step of QA
      tetrapeptide assembly on TrsII. These data show for the first time a functional
      interaction between nonribosomal peptide synthesis and fatty acid synthesis.

PMID- 15569691
TI  - Mitochondrial trans-2-enoyl-CoA reductase of wax ester fermentation from Euglena
      gracilis defines a new family of enzymes involved in lipid synthesis.
AB  - Under anaerobiosis, Euglena gracilis mitochondria perform a malonyl-CoA
      independent synthesis of fatty acids leading to accumulation of wax esters, which
      serve as the sink for electrons stemming from glycolytic ATP synthesis and
      pyruvate oxidation. An important enzyme of this unusual pathway is trans-2-enoyl
      CoA reductase (EC 1.3.1.44), which catalyzes reduction of enoyl-CoA to acyl-CoA.
      Trans-2-enoyl-CoA reductase from Euglena was purified 1700-fold to
      electrophoretic homogeneity and was active with NADH and NADPH as the electron
      donor. The active enzyme is a monomer with molecular mass of 44 kDa. The amino
      acid sequence of tryptic peptides determined by electrospray ionization mass
      spectrometry were used to clone the corresponding cDNA, which encoded a
      polypeptide that, when expressed in Escherichia coli and purified by affinity
      chromatography, possessed trans-2-enoyl-CoA reductase activity close to that of
      the enzyme purified from Euglena. Trans-2-enoyl-CoA reductase activity is present
      in mitochondria and the mRNA is expressed under aerobic and anaerobic conditions.
      Using NADH, the recombinant enzyme accepted crotonyl-CoA (km=68 microm) and trans
      2-hexenoyl-CoA (km=91 microm). In the crotonyl-CoA-dependent reaction, both NADH
      (km=109 microm) or NADPH (km=119 microm) were accepted, with 2-3-fold higher
      specific activities for NADH relative to NADPH. Trans-2-enoyl-CoA reductase
      homologues were not found among other eukaryotes, but are present as hypothetical
      reading frames of unknown function in sequenced genomes of many proteobacteria
      and a few Gram-positive eubacteria, where they occasionally occur next to genes
      involved in fatty acid and polyketide biosynthesis. Trans-2-enoyl-CoA reductase
      assigns a biochemical activity, NAD(P)H-dependent acyl-CoA synthesis from enoyl
      CoA, to one member of this gene family of previously unknown function.

PMID- 15569692
TI  - Nuclear translocation of caspase-3 is dependent on its proteolytic activation and
      recognition of a substrate-like protein(s).
AB  - Caspase-3 is thought to play an important role(s) in the nuclear morphological
      changes that occur in apoptotic cells and many nuclear substrates for caspase-3
      have been identified despite the cytoplasmic localization of procaspase-3.
      Therefore, whether activated caspase-3 is localized in the nuclei and how active
      caspase-3 has access to its nuclear targets are important and unresolved
      questions. Here we confirmed nuclear localizations for both caspase-3-p17 and
      caspase-3-p12 subunits of active caspase in apoptotic cells using subcellular
      fractionation analysis. We also prepared polyclonal and monoclonal antibodies
      specific for active caspase-3 to define the subcellular localization of active
      caspase-3. Immunocytochemical observations using anti-active caspase-3 antibodies
      showed nuclear accumulation of active caspase-3 during apoptosis. In addition,
      caspase-3, but not caspase-7, translocated from the cytoplasm into the nucleus
      after induction of apoptosis. Mutations at the cleavage site between the p17 and
      p12 subunits and the substrate recognition site for the P3 amino acid of the DXXD
      substrate cleavage motif inhibited nuclear translocation of caspase-3, indicating
      that nuclear transport of active caspase-3 required proteolytic activation and
      substrate recognition. These results suggest that active caspase-3 is
      translocated in association with a substrate-like protein(s) from the cytoplasm
      into the nucleus during progression through apoptosis.

PMID- 15569693
TI  - The CMRF58 antibody recognizes a subset of CD123hi dendritic cells in allergen
      challenged mucosa.
AB  - CD123(hi) CD11c(-) dendritic cells (CD123(hi) DC) are a distinct subset of human
      DC present in bone marrow, blood, lymphoid organs, and peripheral tissues.
      Pathogen stimulation, cytokine, or CD40 ligation induces CD123(hi) DC maturation,
      involving a shift from their innate immune to cognate antigen-presenting
      functions. In this study, we revealed that blood CD123(hi) DC in the presence of
      cytokine (granulocyte macrophage-colony stimulating factor and interleukin-3)
      undergo progressive, step-wise maturation through an "early" stage, delineated by
      expression of the antigen detected by the new monoclonal antibody CMRF58
      (CD123(hi)CMRF58(+)CD40(-)CD86(-)CD83(-)) to the "late" stage with costimulatory
      antigen expression (CD123(hi)CMRF58(+)CD40(+)CD86(+)CD83(+/-)). In this early
      stage, cytokine-maintained CD123(hi) DC do not display changes in their
      morphology, no longer produce interferon-alpha (IFN-alpha) in response to
      bacteria, and develop the capacity to induce proliferation and polarization of
      allogeneic T cells. CD123(hi)CMRF58(+) DC, phenotypically similar to in vitro
      cytokine-maintained CD123(hi) DC, were not detected in tonsil but are present in
      allergen-challenged nasal mucosa of allergic individuals. Thus, CD123(hi) DC in
      certain tissue environments such as allergen-challenged nasal mucosa share a
      common CD123(hi)CMRF58(+) phenotype with in vitro cytokine-maintained blood
      CD123(hi) DC characterized by lack of IFN-alpha production.

PMID- 15569694
TI  - Select forms of tumor cell apoptosis induce dendritic cell maturation.
AB  - Dendritic cells (DC) play a crucial role in initiating immune responses to
      tumors. DC can efficiently present antigens from apoptotic tumor cells, but
      apoptotic cells are thought to lack the inflammatory signals required to induce
      DC maturation. Here, we show that apoptosis of 67NR mouse carcinoma cells via the
      Fas (CD95) pathway or induced by the anticancer drug bortezomib (PS-341) but not
      by ultraviolet irradiation is associated with the production of maturation
      signals for DC. These data have important implications for the effects of
      chemotherapy on antitumor immunity in solid and hematologic malignancies.

PMID- 15569695
TI  - Impact of LL-37 on anti-infective immunity.
AB  - Host defense peptides (often called cationic antimicrobial peptides) have
      pleiotropic immunomodulatory functions. The human host defense peptide LL-37 is
      up-regulated at sites of infection and has little or no antimicrobial activity in
      tissue-culture media but under the same conditions, demonstrates immunomodulatory
      effects on epithelial cells, monocytes, and dendritic cells (DC). These effects
      include the induction of chemokine production in a mitogen-activated protein
      kinase-dependent manner in epithelial cell lines and monocytes and profound
      alterations of DC differentiation, resulting in the capacity to enhance a T
      helper cell type 1 response. Although the exact mechanisms of interaction between
      LL-37 and these cell types have not been elucidated, there is evidence for
      specific (i.e., receptor-mediated) and nonspecific interactions. The relative
      significance of the direct antimicrobial activities and immunomodulatory
      properties of LL-37 and other cationic host defense peptides in host defense
      remains unresolved. To demonstrate that antimicrobial activity was not
      necessarily required for protection in vivo, model peptides were synthesized and
      tested for antimicrobial and immunomodulatory activities. A peptide with no
      antimicrobial activity was found to be protective in animal models of
      Staphylococcus aureus and Salmonella infection, implying that a host defense
      peptide can protect by exerting immunomodulatory properties.

PMID- 15569696
TI  - Mannose-binding lectin enhances phagocytosis and killing of Neisseria
      meningitidis by human macrophages.
AB  - Deficiency of mannose-binding lectin (MBL) is probably the most common human
      immunodeficiency and is associated with an increased risk of mucosally acquired
      infections including meningococcal disease. Tissue macrophages are an important
      component of mucosal defense, and so we determined the effect of MBL on uptake of
      meningococci by human monocyte-derived macrophages. Opsonization with MBL
      significantly increased the capture and doubled the amount of internalization of
      Neisseria meningitidis. Inhibition of f-actin polymerization indicated that MBL
      exerted this effect by a dose-dependent acceleration of uptake into phagosomes,
      which was maximal within the normal physiological concentration of MBL (1.5
      microg/ml) and was independent of scavenger receptors. MBL accelerated the
      acquisition and subsequent loss of the early endosome marker, early endosomal
      antigen-1, and enhanced the acquisition of the late endosomal marker, lysosome
      associated membrane protein-1. MBL reduced the survival of meningococci within
      macrophages by more than half, despite the increased uptake of organisms, and
      significantly reduced the number of viable extracellular bacteria by 80%. We
      conclude that MBL is a dependent opsonin able to accelerate microbial uptake and
      killing. These results suggest that MBL could modify disease susceptibility by
      modulating macrophage interactions with mucosal organisms at the site of initial
      acquisition.

PMID- 15569697
TI  - Blockade of PSGL-1 attenuates CD14+ monocytic cell recruitment in intestinal
      mucosa and ameliorates ileitis in SAMP1/Yit mice.
AB  - The pathogenesis of Crohn's disease (CD) is not known. However, monocytes and
      macrophages are thought to play important roles in the development of mucosal
      inflammation. Therefore, in this study, we examined the role of monocyte
      endothelial cell interactions in senescence-accelerated mouse P1 (SAMP1)/Yit
      mice, a murine model of spontaneous ileitis. Fluorescence-labeled CD14+ monocytic
      cells isolated from the spleen and mesenteric lymph nodes of AKR/J (control) mice
      were injected into the tail veins of recipient (AKR/J and SAMP1/Yit) mice, and
      migration in the postcapillary venules (PCV) of Peyer's patches, submucosal
      venules, and villus microvessels of the terminal ileum was monitored by using an
      intravital microscope. Rolling and adhesion of CD14+ monocytic cells in the PCV
      of Peyer's patches and microvessels of the terminal ileum were increased in
      SAMP1/Yit mice. An immunohistochemical study showed increased expression of P
      selectin glycoprotein-1 (PSGL-1), P-selectin, and vascular cell adhesion molecule
      1 in the terminal ileum of SAMP1/Yit mice. Antibodies against these three
      adhesion molecules significantly inhibited adhesion of CD14+ monocytic cells to
      the PCV of Peyer's patches and microvessels of the terminal ileum, treatment with
      an anti-PSGL-1 monoclonal antibody (mAb) showing the strongest suppressive
      effect. Anti-PSGL-1 mAb also attenuated T cell adhesion in microvessels of
      intestinal mucosa. In addition, periodical administration of an anti-PSGL-1 mAb
      for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice. The results
      suggest that PSGL-1-P-selectin interaction plays an important role in monocyte
      endothelial cell interactions and the development of ileitis in a murine model of
      CD and that the blockade of this adhesion molecule may be a novel strategy for
      treating CD.

PMID- 15569698
TI  - The role of circadian rhythmicity in reproduction.
AB  - Circadian rhythmicity is evident in a wide range of physiological systems
      including the reproductive axis. The recent discoveries of rhythmic clock gene
      expression in peripheral tissues, including reproductive tissue, suggests that
      they may play an important role in optimizing fertility. The evidence for
      rhythmic control of reproduction from studies in laboratory animals is reviewed
      and where possible this includes evidence from human studies. Clock genes are
      highly conserved across species including humans and there is no reason to
      suggest that they are functionless in humans. The challenge issued here is for
      researchers to probe their function and the consequences of their disruption in
      both animal and human reproduction.

PMID- 15569699
TI  - Cell-free fetal DNA in maternal blood: kinetics, source and structure.
AB  - The kinetics and structure of cell-free fetal DNA in maternal plasma is currently
      under investigation. Plasma fetal DNA seems quite stable albeit cleared rapidly
      following birth, suggesting continuous fetal DNA release into the maternal
      circulation during pregnancy. However, to understand better the kinetics of
      circulating DNA, studies to determine the biological (structural) form in which
      fetal and maternal DNA exist and the mechanisms underlying variation in plasma
      are warranted to ensure quantitative diagnostic reliability. It is likely that
      circulating fetal DNA is released from fetal and/or placental cells undergoing
      apoptosis. Thus, the majority of fetal DNA is proposed to circulate in membrane
      bound vesicles (apoptotic bodies). This review summarizes the latest reports in
      this field.

PMID- 15569700
TI  - Fertility in female cancer survivors: pathophysiology, preservation and the role
      of ovarian reserve testing.
AB  - The improved long-term survival of adolescents and young women treated for cancer
      has resulted in an increased focus on the effects of chemotherapy on ovarian
      function and its preservation. These women may seek advice and treatment
      regarding their reproductive status, including ways of preserving their fertility
      and preventing a premature menopause--factors that can have a profound impact on
      their quality of life. This article comprehensively reviews ovarian reserve
      testing (ORT) in general. Special emphasis is placed on patients with cancer,
      including the pathophysiology of gonadal damage following chemotherapy, fertility
      preservation and the potential role of ORT. Baseline parameters of ovarian
      reserve [FSH LH, estradiol, inhibin B and anti-Mullerian hormone (AMH)] have not
      yet performed sufficiently well in predicting poor outcome in assisted
      reproduction, but biochemical markers of ovarian reserve appear to be better than
      chronological age. Inhibin B and AMH show potential for future use. Dynamic
      testing appears to show much promise, especially stimulated levels of inhibin B
      and estradiol. The most promising tests of ovarian reserve are the biophysical
      markers, where total antral follicle count was found to be most discriminatory
      followed by ovarian volume. Combination of biochemical, biophysical and clinical
      markers of ovarian reserve may also improve predictive capacity. However, there
      is a lack of data pertinent to ORT in cancer. As yet there is no single
      clinically useful test to predict ovarian reserve accurately. Patients with
      cancer represent a distinct cohort who have particular concerns about their
      future fertility and the possibility of a premature menopause, they can benefit
      greatly from knowledge of their functional ovarian reserve. Large, prospective,
      randomized, adequately controlled studies specific to different geographical
      areas are required in a control population of comparable reproductive age to
      determine the potential role of ORT in clinical practice.

PMID- 15569701
TI  - The chromosomal analysis of human oocytes. An overview of established procedures.
AB  - The cytogenetic survey of mature human oocytes has been and remains a subject of
      great interest because of the prevalence of aneuploidy of maternal origin in
      abnormal human conceptuses, and the lack of understanding about the non
      disjunction processes in human meiosis. The first attempts to analyse the
      chromosomal content of human female gametes were made in the early 1970s, and led
      to limited data because of the paucity of materials and the inadequacy of the
      procedure used. The years to follow brought a resurgence of interest in this
      field, because of the development of human IVF techniques which made oocytes
      unfertilized in vitro available for cytogenetic analysis. Numerous studies have
      since been performed. However, the difficulties in obtaining good chromosome
      preparations and of performing accurate chromosome identification have reduced
      the viability of these studies, resulting in large variations in the reported
      incidences of chromosomal abnormalities. The further introduction of new
      procedures for oocyte fixation and the screening of large oocyte samples have
      allowed more reliable data to be obtained and to identify premature chromatid
      separation as a major mechanism in aneuploidy occurrence. The last decade has
      been privileged to witness the adaptation of molecular cytogenetic techniques to
      human oocytes, and thus various powerful procedures have been tried not only on
      female gametes, but also on polar bodies, involving sequential and multicolour
      fluorescent in situ hybridization (FISH) labelling, comparative genomic
      hybridization (CGH), spectral karyotyping and alternative methods such as primed
      in situ labelling (PRINS) and peptide nucleic acid (PNA) techniques. A large body
      of data has been obtained, but these studies also display a great variability in
      the frequency of abnormalities, which may be essentially attributable to the
      technical limitations of these in situ methods when applied to human oocytes.
      However, molecular cytogenetic approaches have also evidenced the co-existence of
      both whole chromosome non-disjunction and chromatid separation in maternal
      aneuploidy. In addition, the extension of these techniques to oocyte polar body
      materials has provided additional data on the mechanism of meiotic
      malsegregation. Improvements of some of these techniques have already been
      reported. The further development of new approaches for the in situ analysis of
      human meiosis will increase the impact of cytogenetic investigation of human
      oocytes in the understanding of aneuploidy processes in humans.

PMID- 15569702
TI  - Preimplantation genetic diagnosis and chromosome analysis of blastomeres using
      comparative genomic hybridization.
AB  - Numerical chromosome errors are known to be common in early human embryos and
      probably make a significant contribution to early pregnancy loss and implantation
      failure in IVF patients. Over recent years fluorescent in situ hybridization
      (FISH) has been used to document embryonic aneuploidies. Many IVF laboratories
      perform preimplantation genetic diagnosis (PGD) with FISH to select embryos that
      are free from some aneuploidies in an attempt to improve implantation, pregnancy
      and live birth rates in particular categories of IVF patients. The usefulness of
      FISH is limited because only a few chromosomes can be detected simultaneously in
      a single biopsied cell. Complete karyotyping at the single cell level can now be
      achieved by comparative genomic hybridization (CGH). CGH enables not only
      enumeration of all chromosomes but gives a more complete picture of the entire
      length of each chromosome and has demonstrated that chromosomal breakages and
      partial aneuploidies exist in embryos. CGH has provided invaluable information
      about the extent of mosaicism and aneuploidy of all chromosomes in early human
      conceptuses. CGH has been applied to clinical PGD and has resulted in the birth
      of healthy babies from embryos whose full karyotype was determined in the
      preimplantation phase.

PMID- 15569703
TI  - Dynamics of photosystem II: a proteomic approach to thylakoid protein complexes.
AB  - Oxygenic photosynthesis produces various radicals and active oxygen species with
      harmful effects on photosystem II (PSII). Such photodamage occurs at all light
      intensities. Damaged PSII centres, however, do not usually accumulate in the
      thylakoid membrane due to a rapid and efficient repair mechanism. The excellent
      design of PSII gives protection to most of the protein components and the damage
      is most often targeted only to the reaction centre D1 protein. Repair of PSII via
      turnover of the damaged protein subunits is a complex process involving (i)
      highly regulated reversible phosphorylation of several PSII core subunits, (ii)
      monomerization and migration of the PSII core from the grana to the stroma
      lamellae, (iii) partial disassembly of the PSII core monomer, (iv) highly
      specific proteolysis of the damaged proteins, and finally (v) a multi-step
      replacement of the damaged proteins with de novo synthesized copies followed by
      (vi) the reassembly, dimerization, and photoactivation of the PSII complexes.
      These processes will shortly be reviewed paying particular attention to the
      damage, turnover, and assembly of the PSII complex in grana and stroma thylakoids
      during the photoinhibition-repair cycle of PSII. Moreover, a two-dimensional Blue
      native gel map of thylakoid membrane protein complexes, and their modification in
      the grana and stroma lamellae during a high-light treatment, is presented.

PMID- 15569704
TI  - Drought controls on H2O2 accumulation, catalase (CAT) activity and CAT gene
      expression in wheat.
AB  - Plants co-ordinate information derived from many diverse external and internal
      signals to ensure appropriate control of gene expression under optimal and stress
      conditions. In this work, the relationships between catalase (CAT) and H2O2
      during drought in wheat (Triticum aestivum L.) are studied. Drought-induced H2O2
      accumulation correlated with decreases in soil water content and CO2
      assimilation. Leaf H2O2 content increased even though total CAT activity doubled
      under severe drought conditions. Diurnal regulation of CAT1 and CAT2 mRNA
      abundance was apparent in all conditions and day/night CAT1 and CAT2 expression
      patterns were modified by mild and severe drought. The abundance of CAT1
      transcripts was regulated by circadian controls that persisted in continuous
      darkness, while CAT2 was modulated by light. Drought decreased abundance, and
      modified the pattern, of CAT1 and CAT2 mRNAs. It was concluded that the complex
      regulation of CAT mRNA, particularly at the level of translation, allows precise
      control of leaf H2O2 accumulation.

PMID- 15569705
TI  - Photoinhibition and drought in Mediterranean woody saplings: scaling effects and
      interactions in sun and shade phenotypes.
AB  - Interacting effects of high light and drought on the performance of sun and shade
      phenotypes were experimentally undertaken following survival, chlorophyll
      fluorescence and gas exchange in 2-year-old saplings of four Mediterranean trees
      (Quercus ilex and Q. coccifera as water-saving species, and Pistacia lentiscus
      and P. terebinthus as water-spending species). Half of the saplings were grown in
      full sunlight and the other half in the shade (6% sunlight). Half of each
      combination of species-phenotype was exposed to high light during a simulated
      late-summer drought. Light absorptance and gas exchange were scaled up to the
      whole plant with the 3-D geometrical model, Y-Plant. Quercus species were more
      plastic and tolerated high light and water stress better than Pistacia species,
      surviving longer and in drier soils, and exhibiting a less pronounced
      photoinhibition. There was no evidence of disadvantage for shade phenotypes under
      high light with increasing drought. By contrast, shade phenotypes survived longer
      despite larger initial decreases in photochemical efficiency and higher
      sensitivity to drought than sun phenotypes. The enhanced control of transpiration
      during drought in water-saving versus water-spending species (and also in shade
      versus sun phenotypes in three out of the four species) allowed extended
      survival. Photoinhibition reduced whole crown carbon gain in high light by c. 3%
      and affected significantly more the shaded leaves of a given plant (reducing
      their carbon gain by up to 7%) than those exposed to direct sunlight. Despite
      this apparently minor impact, whole plant carbon gain reduction by
      photoinhibition negatively correlated with survival and drought tolerance. The
      implications for succession and forest regeneration in arid environments,
      particularly under a global change scenario, are discussed.

PMID- 15569706
TI  - Actin expression is induced and three isoforms are differentially expressed
      during germination in Zea mays.
AB  - Previous analysis of actin in a dicotyledonous plant, Phaseolus vulgaris (or
      common bean), showed very low actin levels in cotyledons but they were
      concentrated in the embryo axis. Upon imbibition, actin expression increased 5
      fold and a maximum of four actin isoforms were observed, two of them transient
      and two major ones were steadily expressed. In this work, analysis of the actin
      expression in a monocotyledonous plant, Zea mays (or maize), and over a longer
      period of germination/growth, showed that striking similarities exist. Actin is
      present in all the seed components, but it is mainly concentrated in the embryo
      axis. The expression of maize actin was induced during post-imbibition at both
      the protein and mRNA levels. Sharp increases in actin appeared from 24-48 h and
      again from 72-96 h. A more modest and steady actin mRNA increase in expression
      was observed; however, it did not appear as dramatic as in the case of common
      bean due to the presence of readily detectable amounts of message in the dry
      maize seed. The isoform distribution in the dry seed showed a pattern of at least
      three isovariants of pIs approximately 5.0, 5.1, and 5.2, which were
      differentially expressed at the various post-imbibition times analysed. Two of
      the actin isoforms at 48 h post-imbibition cross-reacted with a phosphotyrosine
      specific antibody and they are the product of three expressed genes as shown by
      in vitro translation assays. These data indicate that maize actin protein and
      mRNA expression is induced upon the trigger of germination, and the isoform
      expression kinetics and patterns resemble those from bean, suggesting that, in
      both species, actin expression at these early germination/growth stages is a
      highly regulated event.

PMID- 15569707
TI  - Regulation of lysine catabolism in Arabidopsis through concertedly regulated
      synthesis of the two distinct gene products of the composite AtLKR/SDH locus.
AB  - Lysine catabolism in plants is initiated by a bifunctional LKR/SDH (lysine
      ketoglutarate reductase/saccharopine dehydrogenase) enzyme encoded by a single
      LKR/SDH gene. Yet, the AtLKR/SDH gene of Arabidopsis also encodes a second gene
      product, namely a monofunctional SDH. To elucidate the regulation of lysine
      catabolism in Arabidopsis through these two gene products of the AtLKR/SDH gene,
      an analysis was carried out on the effects of the hormones, abscisic acid and
      jasmonate, as well as various metabolic and stress signals, including lysine
      itself, on their mRNA and protein levels. The response of the two gene products
      to the various treatments was only partially co-ordinated, but the levels of the
      monofunctional SDH mRNA and protein were always in excess over their bifunctional
      LKR/SDH counterparts. These results suggest that lysine catabolism is regulated
      primarily by the first enzyme LKR, while the excess level of SDH enables
      efficient flux of lysine catabolism following the LKR step. Analysis of
      transgenic plants expressing beta-glucoronidase fusion constructs with the
      AtLKR/SDH and monofunctional AtSDH promoters demonstrated that transcriptional
      regulation contributes to the modulation of expression of the bifunctional
      LKR/SDH and monofunctional SDH gene products in response to hormonal and
      metabolic signals. To test whether the enhanced expression of the LKR/SDH gene
      under various hormonal and metabolic signals is correlated with enhanced lysine
      catabolism, wild-type Arabidopsis and a knockout mutant lacking lysine catabolism
      were exposed to abscisic acid and sugar starvation. Free lysine accumulated to
      significantly higher levels in this knockout mutant than in the wild-type plants.

PMID- 15569708
TI  - Experimental analysis of the role of water and carbon in tree stem diameter
      variations.
AB  - The variations of stem diameter as they can be accurately measured by Linear
      Variable Differential Transformer (LVDT) reflect the addition of four components:
      irreversible radial growth, reversible living-cell dehydration/rehydration,
      thermal expansion and contraction, and expansion of dead conducting elements due
      to the increase and relaxation of internal tensions. The correct interpretation
      of LVDT signals, with respect to the practical applications, should make an exact
      distinction between these four components. This paper describes a set of two
      experiments with potted hybrid walnut trees. Double girdling, water stress, and
      duration of the day versus night periods were used in the phytotron as
      experimental factors to induce variations of the carbon and water status of plant
      tissues. The latter were assessed, respectively, by water potential and
      transpiration, and by local stem respiration and carbohydrate content. The
      results are interpreted in terms of carbon or water limitation effects on stem
      diameter variations where radial growth and tissue elasticity could be
      distinguished. Moreover, they suggest no or very low involvement of CO2
      originating from a distance, i.e. carried by the transpirational flux of xylem
      sap, in the total stem CO2 efflux rate.

PMID- 15569709
TI  - Kinetochore-driven formation of kinetochore fibers contributes to spindle
      assembly during animal mitosis.
AB  - It is now clear that a centrosome-independent pathway for mitotic spindle
      assembly exists even in cells that normally possess centrosomes. The question
      remains, however, whether this pathway only activates when centrosome activity is
      compromised, or whether it contributes to spindle morphogenesis during a normal
      mitosis. Here, we show that many of the kinetochore fibers (K-fibers) in
      centrosomal Drosophila S2 cells are formed by the kinetochores. Initially,
      kinetochore-formed K-fibers are not oriented toward a spindle pole but, as they
      grow, their minus ends are captured by astral microtubules (MTs) and transported
      poleward through a dynein-dependent mechanism. This poleward transport results in
      chromosome bi-orientation and congression. Furthermore, when individual K-fibers
      are severed by laser microsurgery, they regrow from the kinetochore outward via
      MT plus-end polymerization at the kinetochore. Thus, even in the presence of
      centrosomes, the formation of some K-fibers is initiated by the kinetochores.
      However, centrosomes facilitate the proper orientation of K-fibers toward spindle
      poles by integrating them into a common spindle.

PMID- 15569710
TI  - Nontranscriptional modulation of intracellular Ca2+ signaling by ligand
      stimulated thyroid hormone receptor.
AB  - Thyroid hormone 3,5,3'-tri-iodothyronine (T3) binds and activates thyroid hormone
      receptors (TRs). Here, we present evidence for a nontranscriptional regulation of
      Ca2+ signaling by T3-bound TRs. Treatment of Xenopus thyroid hormone receptor
      beta subtype A1 (xTRbetaA1) expressing oocytes with T3 for 10 min increased
      inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ wave periodicity. Coexpression
      of TRbetaA1 with retinoid X receptor did not enhance regulation. Deletion of the
      DNA binding domain and the nuclear localization signal of the TRbetaA1 eliminated
      transcriptional activity but did not affect the ability to regulate Ca2+
      signaling. T3-bound TRbetaA1 regulation of Ca2+ signaling could be inhibited by
      ruthenium red treatment, suggesting that mitochondrial Ca2+ uptake was required
      for the mechanism of action. Both xTRbetaA1 and the homologous shortened form of
      rat TRalpha1 (rTRalphaDeltaF1) localized to the mitochondria and increased O2
      consumption, whereas the full-length rat TRalpha1 did neither. Furthermore, only
      T3-bound xTRbetaA1 and rTRalphaDeltaF1 affected Ca2+ wave activity. We conclude
      that T3-bound mitochondrial targeted TRs acutely modulate IP3-mediated Ca2+
      signaling by increasing mitochondrial metabolism independently of transcriptional
      activity.

PMID- 15569711
TI  - Progenitor cells of the testosterone-producing Leydig cells revealed.
AB  - The cells responsible for production of the male sex hormone testosterone, the
      Leydig cells of the testis, are post-mitotic cells with neuroendocrine
      characteristics. Their origin during ontogeny and regeneration processes is still
      a matter of debate. Here, we show that cells of testicular blood vessels, namely
      vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells.
      Resembling stem cells of the nervous system, the Leydig cell progenitors are
      characterized by the expression of nestin. Using an in vivo model to induce and
      monitor the synchronized generation of a completely new Leydig cell population in
      adult rats, we demonstrate specific proliferation of vascular progenitors and
      their subsequent transdifferentiation into steroidogenic Leydig cells which, in
      addition, rapidly acquire neuronal and glial properties. These findings, shown to
      be representative also for ontogenetic Leydig cell formation and for the human
      testis, provide further evidence that cellular components of blood vessels can
      act as progenitor cells for organogenesis and repair.

PMID- 15569712
TI  - Contrasting nuclear dynamics of the caspase-activated DNase (CAD) in dividing and
      apoptotic cells.
AB  - Although compelling evidence supports the central role of caspase-activated DNase
      (CAD) in oligonucleosomal DNA fragmentation in apoptotic nuclei, the regulation
      of CAD activity remains elusive in vivo. We used fluorescence photobleaching and
      biochemical techniques to investigate the molecular dynamics of CAD. The CAD-GFP
      fusion protein complexed with its inhibitor (ICAD) was as mobile as nuclear GFP
      in the nucleosol of dividing cells. Upon induction of caspase-3-dependent
      apoptosis, activated CAD underwent progressive immobilization, paralleled by its
      attenuated extractability from the nucleus. CAD immobilization was mediated by
      its NH2 terminus independently of its DNA-binding activity and correlated with
      its association to the interchromosomal space. Preventing the nuclear attachment
      of CAD provoked its extracellular release from apoptotic cells. We propose a
      novel paradigm for the regulation of CAD in the nucleus, involving unrestricted
      accessibility of chromosomal DNA at the initial phase of apoptosis, followed by
      its nuclear immobilization that may prevent the release of the active nuclease
      into the extracellular environment.

PMID- 15569713
TI  - The neuronal scaffold protein Shank3 mediates signaling and biological function
      of the receptor tyrosine kinase Ret in epithelial cells.
AB  - Shank proteins, initially also described as ProSAP proteins, are scaffolding
      adaptors that have been previously shown to integrate neurotransmitter receptors
      into the cortical cytoskeleton at postsynaptic densities. We show here that Shank
      proteins are also crucial in receptor tyrosine kinase signaling. The PDZ domain
      containing Shank3 protein was found to represent a novel interaction partner of
      the receptor tyrosine kinase Ret, which binds specifically to a PDZ-binding motif
      present in the Ret9 but not in the Ret51 isoform. Furthermore, we show that Ret9
      but not Ret51 induces epithelial cells to form branched tubular structures in
      three-dimensional cultures in a Shank3-dependent manner. Ret9 but not Ret51 has
      been previously shown to be required for kidney development. Shank3 protein
      mediates sustained Erk-MAPK and PI3K signaling, which is crucial for tubule
      formation, through recruitment of the adaptor protein Grb2. These results
      demonstrate that the Shank3 adaptor protein can mediate cellular signaling, and
      provide a molecular mechanism for the biological divergence between the Ret9 and
      Ret51 isoform.

PMID- 15569714
TI  - Cadherin activity is required for activity-induced spine remodeling.
AB  - Neural activity induces the remodeling of pre- and postsynaptic membranes, which
      maintain their apposition through cell adhesion molecules. Among them, N-cadherin
      is redistributed, undergoes activity-dependent conformational changes, and is
      required for synaptic plasticity. Here, we show that depolarization induces the
      enlargement of the width of spine head, and that cadherin activity is essential
      for this synaptic rearrangement. Dendritic spines visualized with green
      fluorescent protein in hippocampal neurons showed an expansion by the activation
      of AMPA receptor, so that the synaptic apposition zone may be expanded. N
      cadherin-venus fusion protein laterally dispersed along the expanding spine head.
      Overexpression of dominant-negative forms of N-cadherin resulted in the
      abrogation of the spine expansion. Inhibition of actin polymerization with
      cytochalasin D abolished the spine expansion. Together, our data suggest that
      cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical
      for the remodeling of synaptic apposition zone.

PMID- 15569715
TI  - Phosphate deprivation induces transfer of DGDG galactolipid from chloroplast to
      mitochondria.
AB  - In many soils plants have to grow in a shortage of phosphate, leading to
      development of phosphate-saving mechanisms. At the cellular level, these
      mechanisms include conversion of phospholipids into glycolipids, mainly
      digalactosyldiacylglycerol (DGDG). The lipid changes are not restricted to
      plastid membranes where DGDG is synthesized and resides under normal conditions.
      In plant cells deprived of phosphate, mitochondria contain a high concentration
      of DGDG, whereas mitochondria have no glycolipids in control cells. Mitochondria
      do not synthesize this pool of DGDG, which structure is shown to be
      characteristic of a DGD type enzyme present in plastid envelope. The transfer of
      DGDG between plastid and mitochondria is investigated and detected between
      mitochondria-closely associated envelope vesicles and mitochondria. This transfer
      does not apparently involve the endomembrane system and would rather be dependent
      upon contacts between plastids and mitochondria. Contacts sites are favored at
      early stages of phosphate deprivation when DGDG cell content is just starting to
      respond to phosphate deprivation.

PMID- 15569716
TI  - HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic
      tail.
AB  - To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human
      immunodeficiency virus (HIV)-1 Nef disrupts the transport of major
      histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV
      infected T cells. However, the mechanism by which Nef does this is unknown. We
      report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I
      from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The
      ability of Nef to target MHC-I from the TGN to lysosomes is dependent on
      expression of the mu1 subunit of adaptor protein (AP) AP-1A, a cellular protein
      complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV
      infected primary T cells, Nef promotes a physical interaction between endogenous
      AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1
      binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our
      evidence suggests that binding of AP-1 to the Nef-MHC-I complex is an important
      step required for inhibition of antigen presentation by HIV.

PMID- 15569717
TI  - Alcohol and gene expression in the central nervous system.
AB  - AIMS: To describe recent research focusing on the analysis of gene and protein
      expression relevant to understanding ethanol consumption, dependence and effects,
      in order to identify common themes. METHODS: A selective literature search was
      used to collate the relevant data. RESULTS: Over 160 genes have been individually
      assessed before or after ethanol administration, as well as in genetically
      selected lines. Techniques for studying gene expression include northern blots,
      differential display, real time reverse transcriptase-polymerase chain reaction
      (RT-PCR) and in situ hybridization. More recently, high throughput functional
      genomic technology, such as DNA microarrays, has been used to examine gene
      expression. Recent gene expression analyses have dramatically increased the
      number of candidate genes (nine array papers have illuminated 600 novel gene
      transcripts that may contribute to alcohol abuse and alcoholism). CONCLUSIONS:
      Although functional genomic experiments (transcriptome analysis) have failed to
      identify a single alcoholism gene, they have illuminated important pathways and
      gene products that may contribute to the risk of alcohol abuse and alcoholism.

PMID- 15569718
TI  - Acute abdominal distension secondary to urinary retention in a patient after
      alcohol withdrawal.
AB  - Several cases of alcohol-induced bladder dysfunction have been reported
      previously, but the mechanism of its development is varied and unclear. We report
      a case of symptomatic abdominal distension due to urinary retention after alcohol
      withdrawal. The timing of the onset suggests that it was induced by alcohol
      withdrawal.

PMID- 15569719
TI  - Upregulation of glutamate receptor subtypes during alcohol withdrawal in rats.
AB  - AIMS: To investigate glutamate receptor subtypes during alcohol withdrawal.
      METHODS: Rats were exposed to severe alcohol intoxication for 84 h and then
      decapitated at 0, 12 and 36 h after the last alcohol dose (n = 7 per group).
      Alcohol was administered five times a day by intragastric intubation. The
      densities of N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors were studied in membranes from the
      forebrain by using the specific ligands [3H]MK-801 and [3H]AMPA, respectively.
      RESULTS: Although no change in the maximal density (B(max)) of [3H]MK-801 binding
      sites was observed at the time of withdrawal, [3H]MK-801 binding was increased by
      49% 12 h into the withdrawal reaction compared with the control group. At 36 h
      post alcohol the B(max) of the [3H]MK-801 binding was still increased by 24%
      compared with the control group; however, this difference was not statistically
      significant. When investigated at the time of withdrawal from chronic alcohol
      intoxication, no significant alterations in the B(max) of the [3H]AMPA binding
      was detected, but 12 h into the withdrawal reaction the [3H]AMPA binding was
      markedly increased by 94%. At 36 h post alcohol the [3H]AMPA binding had returned
      to control levels. No significant alterations in the dissociation constant (K(D))
      of either [3H]MK-801 or [3H]AMPA binding was observed at any time point.
      CONCLUSIONS: NMDA and AMPA receptors are involved in the cerebral hyperactivity
      of alcohol withdrawal.

PMID- 15569720
TI  - MR evaluation of brain perfusion after radiosurgery of cerebral arteriovenous
      malformations: a neuroradiologist's perspective.

PMID- 15569721
TI  - MR evaluation of brain perfusion after radiosurgery of cerebral arteriovenous
      malformations: a surgeon's view.

PMID- 15569722
TI  - Low-flow vascular malformations of the orbit: a new approach to a therapeutic
      dilemma.

PMID- 15569723
TI  - Training, experience, and evidence matter.

PMID- 15569724
TI  - Toward normal perfusion after radiosurgery: perfusion MR Imaging with independent
      component analysis of brain arteriovenous malformations.
AB  - BACKGROUND AND PURPOSE: Brain perfusion is disturbed by cerebral arteriovenous
      malformations (AVMs). Our study was conducted to determine the radiosurgical
      effects on this disturbed perfusion. METHODS: MR perfusion imaging with
      independent component analysis was performed in five healthy subjects and 19
      patients with AVM before and after radiosurgery (every 6 months up to 2 years).
      Perfusion map relative cerebral blood volume (rCBV), cerebral blood flow (rCBF),
      and mean transient time (rMTT) were assessed. Regions of interest (ROIs) on AVM
      target sections were defined as follows: N, AVM nidus; H, the rest of the
      ipsilateral hemisphere; P, immediately posterior to the nidus; A, immediately
      anterior to the nidus; Ar, anterior remote; Pr, posterior remote. Similar ROIs in
      the contralateral hemisphere (N1, H1, P1, A1, Pr1, and Ar1) served as internal
      references. Perfusion ratios of ROI-ROI1 were defined. Nonparameteric Mann
      Whitney U tests and generalized linear models were used for statistical analysis.
      RESULTS: Before radiosurgery, patients' H/H1 rCBV and rCBF ratios were
      significantly higher than those of healthy subjects (P < .005), indicating AVM
      steal. Three types of perilesional perfusion disturbance were observed. From the
      first postradiosurgical follow-up at 6 months, N/N1 rCBV and rCBF ratios
      gradually decreased to 1.0 (both P < .001), whereas rMTT ratios gradually
      increased to 1.0 (P < .015); H/H1, A/A1, and P/P1 rCBV and rCBF ratios decreased
      after radiosurgery (P < .005), indicating reversal of steal toward normal
      perfusion. CONCLUSION: Initial high transnidal flow and perinidal perfusion
      disturbances were demonstrated. They gradually changed toward normal perfusion
      after radiosurgery. This explains, in part, the pathophysiologic factors of AVM
      and therapeutic effects.

PMID- 15569725
TI  - Assessment of transient ischemic attack with diffusion- and perfusion-weighted
      imaging.
AB  - BACKGROUND: Diagnosing TIA can be difficult, since evidence of brain ischemia is
      habitually lacking on CT and conventional MR imaging. It has been suggested that
      patients with acute brain infarction on neuroimaging should be considered stroke
      cases instead of TIA, regardless of duration of symptoms, implying that optimal
      diagnostic methods need to be utilized. We therefore postulated that perfusion
      weighted MR imaging (PW imaging) would be useful in the diagnosis of TIA.
      METHODS: Retrospective analysis of 22 patients with reversible neurologic
      symptoms lasting less than 24 hours, assessed with DW and PW imaging. RESULTS: MR
      imaging was abnormal in 15 patients (68%): 12 had abnormal DW imaging, four had
      both DW and PW imaging defects (all with a mismatch) and three had an isolated PW
      imaging abnormality. There were no differences in symptom duration, stroke
      etiology or cardiovascular risk factors between patients with abnormal MR imaging
      and those with unremarkable scan. Patients with mismatch were more likely to need
      conventional angiography or other cerebrovascular procedures. CONCLUSION: The
      combined use of DW imaging and PW imaging provided evidence of brain ischemia in
      most patients with clinical diagnosis of TIA. Prospective studies using follow-up
      MR imaging are required to determine the outcome of affected tissue, as well as
      the clinical implications of DW-PW imaging abnormalities.

PMID- 15569726
TI  - Fluid-attenuated inversion recovery preparation: not an improvement over
      conventional diffusion-weighted imaging at 3T in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Change in signal intensity due to acute ischemic stroke
      can be detected on diffusion-weighted (DW) images soon after symptom onset. Fluid
      attenuated inversion recovery (FLAIR) DW imaging suppresses signal intensity from
      water and has been suggested to be better than conventional DW imaging as a
      diagnostic imaging technique in acute stroke. We compared the signal intensity-to
      noise ratio (SNR) and contrast-to-noise-ratio (CNR) between ischemic and normal
      tissues by using these two sequences. METHODS: Twenty stroke patients underwent
      imaging less than 6 hours after stroke onset by using both acquisition methods.
      The SNR of six regions of interest in normal brain and one region in ischemic
      brain were compared on both DW imaging and FLAIR DW imaging. We also compared CNR
      in normal and ischemic tissues. The calculated apparent diffusion coefficient
      (ADC) maps from each acquisition technique were similarly assessed. RESULTS: The
      SNR was significantly lower for FLAIR DW imaging than for DW imaging (P < .05).
      The CNR between normal and ischemic tissue was also lower on FLAIR DW imaging (P
      < .05). SNR and CNR of the ADC maps were significantly different (P < .05) for
      all tissues except the putamen and white matter (for SNR and CNR) and globus
      pallidus (for CNR only). CONCLUSION: Ischemic tissue on FLAIR DW imaging was
      significantly less conspicuous than on DW imaging and potentially limits the
      clinical utility of this sequence.

PMID- 15569727
TI  - Diffusion-weighted imaging in the setting of diffuse cortical laminar necrosis
      and hypoxic-ischemic encephalopathy.
AB  - BACKGROUND AND PURPOSE: As is the case for CT scans, MR images may occasionally
      appear deceptively normal unless proper windowing is used. We sought to
      illustrate the necessity for proper windowing and for assessing the gray-white
      matter differentiation on diffusion-weighted (DW) images in the setting of
      hypoxic-ischemic encephalopathy. METHODS: Six comatose patients (age range, 34-56
      years) underwent MR imaging in the early phase (range, 1-5 days) after severe
      anoxic insult. T2-weighted, turbo fluid-attenuated inversion-recovery, and DW
      images were obtained in all six patients, with contrast-enhanced T1-weighted
      images obtained in four and apparent diffusion coefficient (ADC) maps in five of
      the six patients. RESULTS: At presentation, each of the six patients had
      symmetric, uniform hyperintensity in the cortex (mean ADC, 0.35 x 10(-3) mm(2)/s)
      relative to the white matter (mean ADC, 0.91 x 10(-3) mm(2)/s) on DW images. Each
      also had a poor outcome: brain death in four patients and a permanent vegetative
      state in two patients. CONCLUSION: The appearance of the MR images in the setting
      of diffuse cortical laminar necrosis can be deceptive to the unwary radiologist.
      The key to correct interpretation is proper windowing and the marked gray-white
      matter differentiation on spin-echo images but best seen on properly windowed DW
      images in the early subacute phase. This appearance also implies an extremely
      poor outcome, either a permanent vegetative state or brain death.

PMID- 15569728
TI  - Parenchymal abnormalities associated with cerebral venous sinus thrombosis:
      assessment with diffusion-weighted MR imaging.
AB  - BACKGROUND AND PURPOSE: The common entity cerebral venous sinus thrombosis is
      associated with the poorly characterized imaging finding of parenchymal
      abnormalities; diffusion-weighted imaging has offered some insight into these
      manifestations. We assessed the relationship between the diffusion constant from
      apparent diffusion coefficient (ADC) maps in patients with cerebral venous
      thrombosis (CVT) with follow-up imaging findings and clinical outcome. METHODS:
      We evaluated the medical records and T2-weighted MR images of 13 patients with
      CVT complicated by intraparenchymal abnormality. Diffusion-weighted (DW) images
      and ADC maps were evaluated for increased, decreased, or unchanged signal
      intensity and were compared with signal intensity of contralateral, normal
      appearing brain. In addition, ADCs were obtained in nine pixel regions of
      interest in abnormal regions in eight of the 13 patients. RESULTS: Eight patients
      had superficial CVT, and five had superficial and deep CVT. CVT of deep veins was
      associated with deep gray nucleus and deep white matter abnormalities, whereas
      superficial CVT was associated with cortical and subcortical abnormalities.
      Twenty-four nonhemorrhagic lesions were identified in 10 of 13 patients on the
      basis of follow-up imaging findings. Four patients without seizures had lesions
      with decreased diffusion that appeared hyperintense on follow-up T2-weighted
      images, three patients with seizures had lesions with decreased diffusion that
      resolved, and seven patients had lesions with increased diffusion that resolved.
      Three of 10 patients had more than one lesion type. No difference was noted in
      mean ADCs for lesions with decreased diffusion that resolved compared with
      lesions with decreased diffusion that persisted. CONCLUSION: DW imaging in these
      patients disclosed three lesion types: lesions with elevated diffusion that
      resolved, consistent with vasogenic edema; lesions with low diffusion that
      persisted, consistent with cytotoxic edema in patients without seizure activity;
      and lesions with low diffusion that resolved in patients with seizure activity.
      This information may be important in prospectively determining severity of
      irreversible injury and in patient treatment.

PMID- 15569729
TI  - Isolated cortical venous thrombosis presenting as subarachnoid hemorrhage: a
      report of three cases.
AB  - Cortical venous thrombosis (CVT) without concomitant dural sinus thrombosis is an
      uncommon disorder. Isolated CVT usually manifests on imaging studies as focal
      parenchymal hemorrhage or edema. We report three cases of isolated CVT that
      presented with unilateral, localized subarachnoid hemorrhage without parenchymal
      involvement.

PMID- 15569730
TI  - Transcranial color-coded real-time sonographic criteria for occlusion of the
      middle cerebral artery in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Transcranial color-coded real-time sonography (TCCS) is a
      useful tool to evaluate disease of the middle cerebral artery (MCA). This study
      was undertaken to identify TCCS criteria for the diagnosis of MCA stem and MCA
      branch occlusions. METHODS: TCCS and digital subtraction angiography were
      performed in 55 consecutive patients with acute stroke: 10 with MCA stem
      occlusion, the MO group; eight with MCA branch occlusion, the MB group; and 37
      with nonocclusive lesions, the control group. We measured the end-diastolic
      velocity (EDV) of the bilateral MCA stems and calculated the end-diastolic ratio
      by dividing the EDV of the unaffected side by that of the affected side. RESULTS:
      EDV was highest in the control group, and end-diastolic ratio was highest in the
      MO group. An EDV of >25 cm/s indicated a nonocclusive lesion in the MCA, with a
      positive predictive value of 98.4%, a negative predictive value of 81.0%, and an
      accuracy of 93.9%. An EDV of <or=25 cm/s with an end-diastolic ratio of <2.7
      indicated an MCA branch occlusion with a positive predictive value of 85.7%, a
      negative predictive value of 97.2%, and an accuracy of 95.3%. An EDV of <or=25
      cm/s with an end-diastolic ratio of >or=2.7 indicated MCA stem occlusion with a
      positive predictive value of 100%, a negative predictive value of 100%, and an
      accuracy of 100%. CONCLUSION: We developed TCCS criteria for the diagnosis of MCA
      diseases. MCA flow velocity detected by means of TCCS can help identify MCA stem
      occlusion as well as MCA branch occlusion.

PMID- 15569731
TI  - Early uncoupling of cerebral blood flow and metabolism after bilateral thalamic
      infarction.
AB  - Cerebral blood flow and metabolism may be uncoupled in the early phases after
      stroke onset. Prior reports of bilateral thalamic stroke have described
      subsequent coupling of blood flow and metabolism during the chronic stage. We
      chronicled the evolving relationship of blood flow and metabolism with
      concomitant single photon emission CT and positron emission tomography from the
      subacute to chronic phase following bilateral thalamic infarction.

PMID- 15569732
TI  - Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and
      correlation with clinical outcome.
AB  - BACKGROUND AND PURPOSE: Acute lymphocytic leukemia (ALL) is a common malignancy
      of childhood treated with methotrexate (MTX), which is associated with acute
      neurotoxicity. We evaluated diffusion-weighted (DW) and conventional MR images in
      children with ALL and acute MTX-induced neurotoxicity, with clinical correlation.
      METHODS: Five patients aged 12-15 years underwent fluid-attenuated inversion
      recovery (FLAIR), T2-weighted fast spin-echo and gradient-echo, T1-weighted
      gadolinium-enhanced spin-echo, and DW imaging within 24 hours of symptom onset.
      Records were reviewed for the temporal relationship to MTX administration,
      strokelike symptoms, and neurologic outcome. RESULTS: Six strokelike events were
      temporally related to intrathecal MTX given 6-11 days before symptom onset. FLAIR
      images showed abnormal hyperintensity in the callosal splenium in one patient but
      were otherwise normal. Diffusion abnormalities were frontoparietal in three
      events and frontal in one; nonfluent aphasia was seen in all. Bilateral
      frontoparietal diffusion abnormalities were associated with bilateral upper
      extremity weakness, right-sided hemiparesis, or left-sided hemiparesis (one
      patient each); one patient had mild facial droop. Unilateral precentral
      subcortical diffusion abnormality was associated with contralateral motor deficit
      and ipsilateral upper-extremity sensory loss. Strokelike symptoms resolved
      rapidly and were not associated with other signs of encephalopathy. Subsequent
      intrathecal MTX administration was not associated with recurrence in four
      patients. CONCLUSION: Diffusion abnormalities in acute MTX neurotoxicity
      indicated cerebral dysfunction but not necessarily overt structural injury to the
      cerebrum. Subsequent demyelination or gliosis could not be predicted on the basis
      of diffusion abnormalities. A single strokelike episode with diffusion
      abnormalities should not necessarily prompt modification of potentially curative
      chemotherapeutic regimens.

PMID- 15569733
TI  - Brain tumor classification by proton MR spectroscopy: comparison of diagnostic
      accuracy at short and long TE.
AB  - BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of
      brain tumors. The purpose of this study was to determine the influence of the TE
      used in brain tumor classification by comparing the performance of spectra
      obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one
      studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas,
      16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were
      retrospectively selected from a series of 378 consecutive examinations of brain
      masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed
      with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of
      interest were normalized to water. Tumors were classified into four groups
      (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma
      metastases) by means of linear discriminant analysis. The performance of linear
      discriminant analysis at each TE was assessed by using the leave-one-out method.
      RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151
      cases correctly classified) than at long TE (118 [78%] of 151 cases correctly
      classified). Meningioma was the only group that showed higher sensitivity and
      specificity at long TE. Improved results were obtained when both TE were
      considered simultaneously: the suggested diagnosis was correct in 105 (94%) of
      112 cases when both TE agreed, whereas the correct diagnosis was suggested by at
      least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly
      better tumor classification, and results improve when both TE are considered
      simultaneously. Meningioma was the only tumor group in which long TE performed
      better than short TE.

PMID- 15569734
TI  - MR spectroscopy in the diagnosis of cerebral amyloid angiopathy presenting as a
      brain tumor.
AB  - We present two cases of focal, tumefactive, masslike lesions of diffuse cerebral
      amyloid angiopathy (CAA) that presented as areas of increased signal intensity on
      long TR sequences without contrast enhancement or restricted diffusion. MR
      spectroscopy revealed normal metabolite ratios and unremarkable spectra.
      Pathologic tissue showed CAA and CAA with angitis of the CNS. Tumefactive CAA is
      a rare condition, and we describe its characteristics at MR spectroscopy and
      diffusion-weighted imaging.

PMID- 15569735
TI  - Evaluation of cortical atrophy between progressive supranuclear palsy and
      corticobasal degeneration by hemispheric surface display of MR images.
AB  - BACKGROUND AND PURPOSE: Three-dimensional imaging and hemispheric volumetry are
      useful for the assessment of degenerative cortical atrophy. Our purpose was to
      determine the features of cortical atrophy in progressive supranuclear palsy
      (PSP) and corticobasal degeneration (CBD) by means of a hemispheric surface
      display generated with MR images. METHODS: The extent of cortical atrophy was
      evaluated with automated MR hemispheric surface display and volumetry in 19
      patients with PSP and 19 with CBD. RESULTS: Most cortical regions were less
      atrophic in PSP than in CBD. The parietal lobe, paracentral regions, anterior
      middle frontal lobe, and posterior inferior frontal lobe were significantly more
      atrophic in CBD than in PSP, whereas the brainstem was significantly more
      atrophic in PSP. The mean hemisphere-to-intracranial volume ratio was
      significantly greater in patients with PSP (74.5%) than in those with CBD
      (71.4%), whereas the mean brainstem-to-intracranial volume ratio was
      significantly smaller in PSP (1.4%) than in CBD (1.6%). Asymmetry of hemispheric
      volume was significantly larger in the CBD group than in the PSP group.
      CONCLUSION: Hemispheric surface display and volumetry are generally helpful and
      especially useful for the differentiation of PSP and CBD.

PMID- 15569736
TI  - fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's
      Disease.
AB  - BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) has been used to probe basal
      ganglia function in people with presymptomatic Huntington's disease (pre-HD). A
      previous fMRI study in healthy individuals demonstrated activation of the basal
      ganglia during a time-discrimination task. The current study was designed to
      examine the relative sensitivity of fMRI compared with that of behavioral testing
      and morphometric measurements in detecting early neurodegenerative changes
      related to Huntington's disease (HD). METHODS: Pre-HD participants were assigned
      to two groups based on estimated years to diagnosis of manifest disease: close
      <12 years and far >or=12 years. Age at disease onset was estimated using a
      regression equation based on the number of trinucleotide CAG repeats. The time
      discrimination task required participants to determine whether a specified
      interval was shorter or longer than a standard interval of 1200 milliseconds.
      RESULTS: Participants in the close group performed more poorly on the time-task
      discrimination than did control subjects; however, no differences were observed
      between far participants and control subjects. Similarly, close participants had
      reduced bilateral caudate volume relative to that of control subjects, whereas
      far participants did not. On functional imaging, close participants had
      significantly less activation in subcortical regions (caudate, thalamus) than
      control subjects; far participants had an intermediate degree of activation. In
      contrast, far participants had hyperactivation in medial hemispheric structures
      (anterior cingulate, pre-supplementary motor area) relative to close and control
      subjects. CONCLUSION: Hyperactivation of medial prefrontal regions compensated
      for reduced subcortical participation during time discrimination in pre-HD. This
      pattern of brain activation may represent an early neurobiologic marker of
      neuronal dysfunction.

PMID- 15569737
TI  - CNS MR and CT findings associated with a clinical presentation of herpetic acute
      retinal necrosis and herpetic retrobulbar optic neuritis: five HIV-infected and
      one non-infected patients.
AB  - INTRODUCTION: This report demonstrates the spectrum of central nervous system
      (CNS) abnormalities observed on MR imaging and CT studies in 6 patients with
      clinical or pathologic diagnoses of acute retinal necrosis (ARN) and retrobulbar
      optic neuritis (RBON-H) resulting from Herpes Zoster Virus and Cytomegalovirus.
      We discuss the etiologic and pathophysiologic implications regarding these
      findings. METHODS: Standard MR imaging sequences of the whole brain and selected
      high-resolution images of the orbits and globes, from 6 patients, were reviewed
      by three neuroradiologists for consensus interpretation of the findings. Special
      sequences augmenting disease were obtained in individual cases. Axial CT images
      were obtained from two patients using 5mm sequential slices. RESULTS: MR imaging
      findings showed both T2 signal brightening and contrast enhancement in one or
      both optic nerves, optic tracts and lateral geniculate bodies, as well as the
      postsynaptic optic radiations and optic cortex. Similar findings were observed in
      the superior colliculus, lateral midbrain and cerebellum, with multiple potential
      etiologic possibilities regarding pathways of dissemination. Low T2* signal
      (indicating magnetic field susceptibility effects) and CT hyperdensity,
      consistent with prior hemorrhage, were also observed in the optic tracts, optic
      radiations and lateral geniculate bodies. Post-contrast enhancement was observed
      in the meninges and Meckle's cave in one HIV negative patient. CONCLUSION: These
      cases demonstrate CNS imaging findings associated with RBON that are temporally
      related to ARN. They support the hypothesis that RBON can either precede or
      follow ARN and implicate transneuronal, transsynaptic and/or transcerebrospinal
      fluid viral spread by the herpetic family.

PMID- 15569738
TI  - Ophthalmic artery originating from basilar artery: a rare variant.
AB  - The basilar artery as the origin of the ophthalmic artery is extremely rare. A 48
      year-old patient had undergone angiography for suspicion of a right middle
      cerebral artery aneurysm. No aneurysm was detected. Vertebral artery injections
      demonstrated the left ophthalmic artery originating from the basilar trunk.
      Current embryologic theories fall short in explaining this entity. Awareness of
      neuroanatomic variations is of paramount importance in diagnosis and treatment of
      vascular lesions of the brain.

PMID- 15569739
TI  - Training, competency, and credentialing standards for diagnostic cervicocerebral
      angiography, carotid stenting, and cerebrovascular intervention.

PMID- 15569740
TI  - Treatment of internal carotid artery aneurysms with a covered stent: experience
      in 24 patients with mid-term follow-up results.
AB  - BACKGROUND AND PURPOSE: We present our preliminary experience, including mid-term
      angiographic and clinical follow-up results, with an alternative technique for
      the endovascular treatment of intracranial aneurysms in a series of patients.
      This new method, previously described in anecdotal case reports, consists of
      endovascular deployment of an artificial vessel graft (stent graft or covered
      stent) in the parent vessel to exclude the intracranial aneurysm sac from
      circulation. METHODS: Twenty-five internal carotid artery (ICA) aneurysms in 24
      patients were successfully treated by using a Jostent coronary stent graft
      deployed in the parent artery across the aneurysm neck. All except four aneurysms
      were extradural, located in the petrous or cavernous portion of the ICA. The four
      intradural aneurysms were located in the carotico-ophthalmic region. Seventeen
      aneurysms in 16 patients occurred posttraumatically, secondary to motor vehicle
      accidents or surgical injury. RESULTS: Twenty-three aneurysms were immediately
      excluded from circulation after stent graft placement. In two aneurysms, a slow
      contrast material filling (endoleak) into the aneurysm cavity was observed
      immediately after treatment. One was thrombosed, as shown by late control
      angiography; in the other one, a second larger bare stent was used to appose the
      stent graft's distal end to the ICA wall, thus sealing the endoleak into the
      distal graft. No technical adverse event, including vessel dissection, vessel
      perforation, or thromboembolism, occurred with or without clinical consequence.
      No mortality or morbidity developed during or after the procedure, including the
      follow-up period. Two-year control angiography in one patient, 1.5-year control
      angiography in two patients, 1-year control angiography in six patients, and 6
      month control angiography in 12 patients were performed, revealing reconstruction
      of the ICA with no aneurysm recanalization. All symptoms resolved after treatment
      in the patients who had initially presented with mass effect. CONCLUSION: Initial
      anatomic, clinical and mid-term follow-up results in this small series of
      patients are encouraging. This technique has been proved to have potential in the
      reconstructive treatment of intracranial aneurysms. Further research and
      development are needed to optimize the stent graft technology for the
      cerebrovascular system.

PMID- 15569741
TI  - Anatomically shaped internal carotid artery aneurysm in vitro model for flow
      analysis to evaluate stent effect.
AB  - BACKGROUND AND PURPOSE: Stent implantation alone might not be sufficient to
      produce definitive treatment of cerebral aneurysms. Therefore, extended
      experimental work is needed to improve results. We show the feasibility of using
      an in vitro anatomically shaped elastic model for flow evaluation before and
      after stent implantation. METHODS: Based on human vascular casting, an anatomic
      elastic internal carotid artery model, including an aneurysm on the supraclinoid
      portion, was manufactured. The model was connected to a circulatory loop to
      simulate physiological flow. After visualization of the flow by using glass
      particles and laser sheet translumination, the digitally recorded data were
      transferred for computer analysis. Intra-saccular flow pattern changes and the
      vortex velocity reduction induced by the stent were investigated qualitatively
      and quantitatively. RESULTS: The distal neck of the aneurysm behaved as a flow
      divider. Therefore, it was directly exposed to the hemodynamic stress. Inside the
      sac, a well-defined vortex formed and progressed along the wall toward the
      proximal neck. After stent implantation this pattern changed significantly; the
      vortex appeared more dispersed and its residence time increased. The velocity
      reduction was 32%. Velocity peak was observed close to the distal neck in both
      cases. CONCLUSION: In vitro anatomic elastic models are feasible for flow
      evaluation with laser sheet translumination. In our model, stent implantation
      resulted in hemodynamic changes that might favor the exclusion of the aneurysm
      from the circulation and can prevent regrowth of the aneurysmal sac.

PMID- 15569742
TI  - Use of covered stent grafts in the extracranial carotid artery: report of three
      patients with follow-up between 8 and 42 months.
AB  - Currently, most carotid artery pathologic abnormalities resulting in
      pseudoaneurysm formation or stenosis are repaired by surgical intervention.
      Because surgical intervention requires proximal and distal control of the artery,
      pseudoaneurysms near the skull base may be very difficult to repair and pose
      greater risk to the patient. As a result, endovascular techniques have evolved in
      an effort to reduce morbidity associated with surgical techniques. Parent vessel
      occlusion and coil placement are the most frequently used endovascular techniques
      for carotid artery repair of pseudoaneurysms. Intimal hyperplasia is generally
      treated with balloon angioplasty, often in conjunction with uncovered stent
      placement. Parent vessel occlusion may be impractical if the patient is unable to
      tolerate occlusion of that artery. We report our experience in treating three
      patients with carotid artery stent grafts.

PMID- 15569743
TI  - In-stent stenosis as a delayed complication of neuroform stent-supported coil
      embolization of an incidental carotid terminus aneurysm.
AB  - The Neuroform stent is the first microcatheter-delivered stent designed
      specifically for the treatment of cerebral aneurysms. The stent functions
      primarily to provide durable parent vessel protection during the embolization of
      broad-necked cerebral aneurysms. The present case report demonstrates in-stent
      stenosis occurring as a delayed complication of Neuroform stent-supported coil
      embolization of an unruptured cerebral aneurysm.

PMID- 15569744
TI  - Thromboembolic events associated with balloon-assisted coil embolization:
      evaluation with diffusion-weighted MR imaging.
AB  - BACKGROUND AND PURPOSE: Thromboembolic events may occur during or after the
      treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The
      purpose of this study was to determine the frequency of thromboembolic events
      associated with balloon-assisted coil placement and to investigate possible risk
      factors for these events during balloon-assisted coil placement and embolization.
      METHODS: Twenty patients with cerebral aneurysms treated with balloon-assisted
      coil placement and embolization at our institution were included. All patients
      underwent diffusion-weighted (DW) imaging within 6 hours after the procedure. Two
      neuroradiologists reviewed all DW images to detect ischemic lesions. RESULTS:
      Hyperintense lesions compatible with thromboembolic events were detected on DW
      images of four (20%) patients. Three lesions were in the territory of posterior
      circulation, and one was in the territory of anterior circulation. The occurrence
      of new lesions was strongly associated with the number of times the microcatheter
      or coil was repositioned and removed and with the size of the aneurysmal neck (P
      < .01). DW imaging findings did not suggest a strong correlation between the
      occurrence of new ischemic lesions and potential risk factors (maximum balloon
      inflation time, number of times the balloon was inflated, etc.) associated with
      balloon-assisted coil placement and embolization (P > .05). CONCLUSION: The risk
      of thromboembolic events during the treatment of intracranial aneurysms with
      balloon-assisted techniques is not more significant than when conventional GDC
      techniques are used. The only variables found to influence this risk during or
      after balloon-assisted coil placement were microcatheter repositioning, coil
      removal and repositioning, and size of the aneurysmal neck.

PMID- 15569745
TI  - Predictors of outcome after endovascular treatment of cerebral vasospasm.
AB  - BACKGROUND AND PURPOSE: Angioplasty and intra-arterial papaverine are promising
      treatments for severe symptomatic vasospasm after subarachnoid hemorrhage (SAH),
      but there is little information on the clinical factors that predict treatment
      outcome. We sought to determine variables for predicting functional outcome in
      this setting. METHODS: We reviewed 81 consecutive patients with symptomatic
      cerebral vasospasm from aneurysmal SAH treated with percutaneous balloon
      angioplasty or selective intra-arterial papaverine infusion between 1990 and 2000
      (105 procedures). Logistic regression analysis was used to assess the effect of
      various clinical and angiographic factors on outcome. RESULTS: Mean patient age
      was 54 years (range, 29-88 years). Twenty-nine patients (36%) presented with poor
      grade (World Federation of Neurologic Surgeons [WFNS] grade IV or V) SAH.
      Clinical deficits were global in 55 patients (70%), and angiographic vasospasm
      was diffuse in 53 (65%). Endovascular treatment consisted of transluminal
      angioplasty alone (18 procedures, 17%), intra-arterial papaverine infusion (65
      procedures, 62%), or both (22 procedures, 21%). Unequivocal arterial dilatation
      was achieved in all but two patients, and major complications occurred in 2% of
      the procedures. Ten patients (12%) died in the hospital, and 36 (44%) recovered
      poorly. Permanent deficits attributable to cerebral vasospasm were present in 37
      patients (52% of survivors). On multivariate logistic regression analysis,
      advanced age and poor WFNS grade at presentation were predictive of poor clinical
      outcome. CONCLUSION: Advanced age and poor clinical status at the time of SAH
      onset are predictive of poor clinical outcome despite endovascular treatment with
      angioplasty or intra-arterial papaverine in patients with symptomatic vasospasm.

PMID- 15569746
TI  - Blood brain-barrier disruption of nonionic iodinated contrast medium following
      coil embolization of a ruptured intracerebral aneurysm.
AB  - Few reports of temporary disruption of the blood-brain barrier (BBB) following
      neurointerventional procedures, presumably caused by nonionic radiographic
      contrast medium (CM), exist in the literature. We described such a case in a 72
      year-old man presenting with acute subarachnoid hemorrhage, who underwent coil
      embolization of a ruptured anterior communicating artery complex aneurysm. At the
      time of his follow-up CT examination, a large amount of iodine was found in the
      cerebrospinal fluid (CSF). Because of this experience, the iodine concentration
      in the CSF of five other patients who also underwent an intracranial endovascular
      procedure was measured. It was concluded that this increased iodine might have
      been caused by temporary leakage or breakdown of the BBB. Even if the total
      amount of CM may not be excessive, the disproportionately high concentration
      injected into a single vascular territory may pose a unique set of variables
      increasing the risk of BBB disruption.

PMID- 15569747
TI  - Simultaneous bilateral internal carotid artery 3D rotational angiography.
AB  - We simultaneously injected both internal carotid arteries (ICAs) during 3D
      rotational digital subtraction angiography in a patient with a ruptured anterior
      communicating artery (Acom) aneurysm and vasospasm. Shaded surface display (SSD)
      images from this acquisition provided more anatomic detail than did SSD images
      created from individual ICA 3D rotational digital subtraction angriography. In
      the evaluation of complex Acom aneurysms, this technique can facilitate the
      choice of optimal working projections for safer aneurysm coiling.

PMID- 15569748
TI  - Endovascular management of dolichoectasia of the posterior cerebral artery
      report.
AB  - Congenital or nonatherosclerotic dolichoectasia is a rare condition; its
      etiology, natural history, and indications and technique of treatment are not yet
      clarified. During a workup for recent headaches and left-sided paresthesia in a
      48 year-old female patient, brain MR imaging and cerebral angiography showed a
      large dolichoectasia of the P2 segment of the right posterior cerebral artery
      (PCA). The patient passed endovascular testing for occlusion of P2 with both
      balloon test occlusion and selective amytal testing. Endovascular coil occlusion
      of the right PCA dolichoectasia was successfully performed with hydrogel coils.

PMID- 15569749
TI  - Navigation-assisted sclerotherapy of orbital venolymphatic malformation: a new
      guidance technique for percutaneous treatment of low-flow vascular malformations.
AB  - Percutaneous sclerotherapy of orbital low-flow vascular malformations requires
      precise procedural guidance. For the treatment of a patient with an orbital
      venolymphatic malformation, we sought to optimize guidance by combining
      navigation assistance for needle placement with intralesional contrast medium
      injection for assessment of venous drainage. By using a surgical navigation
      system (Vector Vision, BrainLAB, Munich, Germany), multiplanar target lesion
      visualization was performed after fusion of CT and MR imaging data, which allowed
      precise puncture planning.

PMID- 15569750
TI  - Predictors of clinical outcome in patients receiving local intra-arterial
      thrombolysis without subsequent symptomatic intracranial hemorrhage against acute
      middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: The factors that predict favorable outcome after local
      intra-arterial thrombolysis (LIT) remain unknown. We aimed to clarify these
      factors in patients with middle cerebral artery occlusion treated by LIT.
      METHODS: We performed LIT in 26 consecutive patients who had middle cerebral
      artery occlusion with a modified Rankin scale (mRS) score <or=2 before stroke
      onset. We assessed background characteristics, angiographic findings, and mRS
      score at discharge. We compared these factors between patients with good outcome
      (mRS score, <or=2) and those with poor outcome (mRS score, >or=3). RESULTS: The
      duration from symptom onset to hospital admission was 0.96 +/- 0.87 (mean +/- SD)
      hour and from onset of stroke to LIT was 3.78 +/- 1.17 hours. No patients
      developed symptomatic intracerebral hemorrhage or died. Thirteen patients
      achieved good outcomes. No significant differences existed between the two groups
      in baseline National Institutes of Health Stroke Scale (NIHSS) scores, time from
      stroke onset to LIT, blood pressure, early CT signs, or subsequent hemorrhagic
      transformation shown by CT. However, univariate analysis showed that patients
      with good outcomes were younger, more often had absence of hypertension history,
      had better collaterals shown by angiography, and had better recanalization rates
      than those with poor outcomes. NIHSS scores after LIT were lower in patients with
      good outcomes than in patients with poor outcomes. Logistic regression analysis
      indicated improvement of the NIHSS scores by >or=2 immediately after LIT was
      independently associated with good outcome. CONCLUSION: Improvement of the NIHSS
      score by >or=2 immediately after LIT is a useful predictor of patient outcome at
      discharge.

PMID- 15569751
TI  - Access to intra-arterial therapies for acute ischemic stroke: an analysis of the
      US population.
AB  - BACKGROUND AND PURPOSE: Intra-arterial therapies for ischemic stroke offer
      promise as a means to extend the time window for acute treatment. The purpose of
      this study was to identify the percentage of the US population with potential
      access to interventional neuroradiologic expertise within 6 hours of the onset of
      stroke symptoms. METHODS: Hospital locations of interventional neuroradiologists
      were identified from the 2002 roster of the American Society of Interventional
      and Therapeutic Neuroradiology. Data for populations in surrounding regions were
      extracted from US Census 2001 data by zip code. Standard transport speeds for
      emergency medical services were used in our estimates of the population living
      within a 5-hour transport time, which was a 6-hour treatment window less a 1-hour
      door-to-needle time, resulting in a 200-mile radius. A 2-hour transport time, or
      3-hour treatment window, reflected a 65-mile radius. RESULTS: A total of 385
      interventional neuroradiologists were identified, practicing in 45 states. With a
      200-mile radius, 99% of the total US population had access to neurointerventional
      treatment within 6 hours of symptom onset. With a 65-mile radius, 82% of the
      population had access within 3 hours of symptom onset. Alaska and the Mid
      Northwest region covering Idaho, Wyoming, North Dakota, and South Dakota had
      limited coverage. CONCLUSION: Most of the US population has access to
      interventional neuroradiologic expertise for acute stroke therapy. These data
      suggest that interventional therapies that extend the time window for treating
      acute ischemic stroke could have a major effect on public health and merit
      further research development and investment.

PMID- 15569752
TI  - Rheolytic catheter thrombectomy, balloon angioplasty, and direct recombinant
      tissue plasminogen activator thrombolysis of dural sinus thrombosis with
      preexisting hemorrhagic infarctions.
AB  - We describe the case of a 28-year-old obtunded woman who presented with bilateral
      anterior parietal lobe cortical hemorrhages associated with thrombosis of the
      superior sagittal sinus, both transverse and sigmoid sinuses, and multiple
      cortical veins draining into the sagittal sinus. Initial heparin therapy was not
      effective. A combination of AngioJet rheolytic catheter thrombectomy, balloon
      angioplasty, and continuous direct superior sagittal sinus recombinant tissue
      plasminogen activator infusion led to venous recanalization with a successful
      clinical outcome, without worsening of the preexisting intracranial hemorrhages.

PMID- 15569753
TI  - Mechanical thrombectomy of the internal carotid artery and middle cerebral
      arteries for acute stroke by using the retriever device.
AB  - We report a case of mechanical thrombectomy in which a new device, the Retriever,
      was used for acute cerebral ischemia in the setting of extensive occlusion of the
      left internal carotid and middle cerebral arteries. Excellent radiographic and
      clinical results were obtained. The Retriever is currently approved and available
      for foreign body extraction and for intracranial thrombectomy when used as part
      of the Mechanical Embolus Removal in Cerebral Ischemia, or MERCI, clinical trial.
      This device was able to retrieve and remove clots efficiently from the
      intracranial and extracranial circulation, offering a new therapeutic alternative
      in the treatment of acute cerebral ischemic disease.

PMID- 15569754
TI  - Magnetization transfer micro-MR imaging of live excised lamprey spinal cord:
      characterization and immunohistochemical correlation.
AB  - BACKGROUND AND PURPOSE: Membrane constituents may play a key role in the
      magnetization transfer (MT) effect. In lamprey spinal cord, axonal diameters
      range from <1 microm in the dorsal region to 20-40 microm in the ventral region.
      There is a corresponding range of axonal, and hence cell membrane, density. These
      characteristics permit determination of the effect of cell membrane density on
      MT. The purpose of this study was to characterize regional MT effects in lamprey
      spinal cord. METHODS: Excised spinal cords from eight sea lampreys were measured
      with a 9.4-T MR imaging system. MT saturation was applied for spin-echo
      sequences. The MT ratio (MTR) was calculated in each location (dorsal, lateral,
      and ventral columns). Spinal cords from five other lampreys were prepared with an
      antibody to lamprey glial keratin (LCM 29). The percentage of area staining with
      LCM29 was calculated for each location. RESULTS: Mean MTR (+/- SD) for the
      dorsal, lateral, and ventral columns were 62.4 +/- 4.2, 59.2 +/- 2.7, and 56.9 +/
      3.0, respectively; all differences were significant (P < .05). Mean LCM29
      positive areas for the dorsal, lateral, and ventral columns were 85.1%, 69.7%,
      and 50.9%, respectively. MTR and percentage LCM29-positive area were
      significantly correlated (r(2) = 0.98). CONCLUSION: Regional differences in MT
      effect exist in the lamprey spinal cord. MTR is well correlated with percentage
      LCM29-positive area. These results support the hypothesis that membrane
      constituents are at least partly responsible for regional variations in MT
      effect.

PMID- 15569755
TI  - CT fluoroscopy-guided epidural injections: technique and results.
AB  - Lumbar epidural injections are typically performed blindly or with fluoroscopic
      guidance. CT fluoroscopy (CTF) can be used to guide needle placement precisely
      and rapidly, allowing visualization of the optimal needle path and identifying
      potential problems such as severe stenosis and synovial cysts before needle
      insertion. Operator and patient radiation dose is minimal when using the
      intermittent CTF technique and low mAs. By using this technique, just more than
      2000 epidural steroid injections have been performed with no major complications.
      CTF is a useful guidance tool when performing lumbar epidural injections.

PMID- 15569756
TI  - Gadolinium diskography.
AB  - Gadolinium can be used to perform diskography in patients with a documented
      allergy to iodinated contrast material. MR images can be obtained in multiple
      planes with excellent delineation of disk architecture. Dilute gadolinium leaves
      the disk space within a few days of injection.

PMID- 15569757
TI  - Isolated true anterior thoracic meningocele.
AB  - Intrathoracic meningocele is rare and is usually associated with
      neurofibromatosis type I. Most of the reported thoracic meningoceles are not
      strictly anterior in location, but also lateral or anterolateral. We report a
      case of true anterior thoracic meningocele with no associated generalized
      mesenchymal dysplasia.

PMID- 15569758
TI  - Paraplegia and sensory deficit caused by angiotropic large cell lymphoma.
AB  - We report a case of angiotropic large cell lymphoma (ALCL) with central system
      involvement in which there was initially an isolated spinal cord stroke with
      paraplegia. MR imaging of the spinal cord demonstrated increased signal intensity
      in the center of the cord on T2-weighted images and subsequently a cerebral
      lesion in the right temporal lobe. The diagnosis of ALCL was established by brain
      biopsy. An enlarged spinal cord with enhancement after administration of contrast
      material and increased signal intensity on T2-weighted images, while not specific
      for ALCL, may be the first imaging findings of that disease.

PMID- 15569759
TI  - Malformation of cortical and vascular development in one family with parietal
      foramina determined by an ALX4 homeobox gene mutation.
AB  - Vascular and cortical anomalies have been found in a family with parietal
      foramina type 2 (PFM2), which is determined by the ALX4 gene. It is believed that
      ALX4 has a bone-restricted expression. We report a case of PFM with age-related
      size variation in a 4-year-old boy, as well as in his mother, aunt and
      grandfather. MR imaging of the child demonstrates prominent malformations of
      cortical (polymicrogyric cortex with an unusual infolding pattern) and vascular
      development (persistence median prosencephalic vein), associated with high
      tentorial incisure periatrial white matter changes.

PMID- 15569760
TI  - Emery-Dreiffus muscular dystrophy: MR imaging and spectroscopy in the brain and
      skeletal muscle.
AB  - Emery-Dreifuss muscular dystrophy is a rare disorder characterized by childhood
      onset of contractures, humeroperoneal muscle atrophy, and cardiac conduction
      abnormalities. This report presents the cases of two brothers with this dystrophy
      in whom bilateral hypomyelination of the deep periatrial white matter was noted.
      In the hypomyelinated regions, a prominent peak centered at 1.5 parts per million
      was present on short-TE MR spectra likely representing prominence of proteolipids
      in the macromolecular region. Major peaks (N-acetyl-aspartate, creatine, choline,
      and myoinositol) were normal. With respect to muscle changes, atrophy of the
      medial head of the gastrocnemius muscle was noted at MR imaging, and phosphorus
      spectroscopy of this muscle revealed decreased phosphocreatine and inorganic
      phosphate peaks.

PMID- 15569761
TI  - Reversible white matter lesion in methionine adenosyltransferase I/III
      deficiency.
AB  - A 5-year-old boy with methionine adenosyltransferase (MAT) I/III deficiency,
      under treatment for the tentative diagnosis of homocystinuria, presented with
      mildly decreased appetite and sleepiness. MR imaging showed abnormal T1 and T2
      prolongations and reduced diffusion in the cerebral white matter. Clinical
      symptoms and MR imaging findings improved after discontinuation of therapy. We
      speculate that inappropriate treatment might enhance CNS lesions of MAT I/III
      deficiency by causing a reversible vacuolating myelinopathy.

PMID- 15569762
TI  - Dynamic upper airway soft-tissue and caliber changes in healthy subjects and
      snoring patients.
AB  - BACKGROUND AND PURPOSE: The oropharyngeal airways are smaller in those who snore
      than in those who do not. We sought to determine which soft-tissue component
      surrounding the airways contributes to upper airway narrowing in those who snore.
      METHODS: Ten control subjects and 19 snoring patients underwent CT, with 2-mm
      thick axial sections obtained every 0.6 seconds during the respiration cycle at
      the same oropharyngeal level. We selected two sections with the widest and
      narrowest parts of the oropharyngeal airway to measure the anteroposterior and
      lateral dimensions of the airway and the thickness of the bilateral
      parapharyngeal fat pads, pterygoid muscles, and parapharyngeal walls. Mean values
      were calculated for each phase. For each subject, differences were calculated by
      subtracting the values in narrowest phase from those in the widest phase.
      RESULTS: Changes in airway dimension (P < .05) and lateral parapharyngeal wall
      thickness (P < .01) were significantly different between snorers and control
      subjects. Changes in parapharyngeal wall thickness and transverse oropharyngeal
      airway diameter changes were significantly related (P < .01) in those who snored
      but not in control subjects. CONCLUSION: Airway narrowing predominantly occurs in
      the lateral dimension in people who snore. Changes in the lateral pharyngeal wall
      are more important than the parapharyngeal fat pads in airway calibration.
      Narrowing of the upper airway area at the end of the expirium and the beginning
      of the inspirium is thought to be the cause of snoring and due to augmented
      muscle mass and prolonged laxity rather than inadequate activation of the
      pharyngeal dilating muscles.

PMID- 15569763
TI  - Retroclival ecchordosis physaliphora: MR imaging and review of the literature.
AB  - BACKGROUND AND PURPOSE: Ecchordosis physaliphora (EP), found in about 2% of
      autopsies, is a clinically inconspicuous notochordal remnant appearing at the
      dorsal wall of the clivus. To our knowledge, a systematic review of its MR
      features does not exist. The aim of this study was to describe the MR imaging
      findings of incidentally found retroclival EP with special respect to its
      differentiation from intradural chordomas. METHODS: We reviewed 300 consecutive
      1.5-T MR imaging studies that included thin-section transverse T2-weighted images
      of the skull base for the presence of a retroclival EP. In cases in which an EP
      was identified, two neuroradiologists observed MR signal intensity
      characteristics, contrast enhancement, size, form, stalk of EP, and signal
      intensity changes of the adjacent clivus. RESULTS: Five cases with retroclival EP
      were found (incidence, 1.7%). In all cases, the ecchordoses was hyperintense on
      T2-weighted images and hypointense on T1-weighted images. Contrary to the
      reported findings in chordomas, none of the lesions showed contrast enhancement.
      In four cases, there were signal intensity changes in the adjacent clivus. A
      stalklike connection between clivus and EP was seen in three patients.
      CONCLUSION: Because of the benign character of EP and the difficulties in its
      histopathologic differentiation from chordomas, precise knowledge of the
      radiologic characteristics of EP is important. On the basis of these five cases
      and a review of literature, contrast enhancement and the presence of clinical
      symptoms seem to be highly reliable parameters in the differential diagnosis of
      intradural chordoma and EP.

PMID- 15569764
TI  - Combined use of color duplex ultrasonography and B-flow imaging for evaluation of
      patients with carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: Color duplex ultrasonography (CDU) is a standard method
      of noninvasive evaluation of internal carotid artery stenosis (ICAS). B-flow
      imaging (BFI), on the other hand, is a newer method. We investigated the accuracy
      of the two noninvasive tests--CDU and BFI--each separately and as a combination
      of the two tests by comparing with digital subtraction angiography as a reference
      standard. METHODS: We performed CDU, BFI, and digital subtraction angiography on
      95 consecutive patients with ICAS. Separate and combined test results of CDU and
      BFI were compared with digital subtraction angiography results. RESULTS: For
      identifying 70% to 99% ICAS, as CDU criterion, the ratio of internal carotid
      artery to common carotid artery peak systolic velocity had the highest diagnostic
      accuracy (sensitivity, 94%; specificity, 96%). The sensitivity and specificity of
      BFI were 65% and 98%, respectively. With CDU and BFI, results were concordant in
      144 (89%) cases for 70% to 99% ICAS. Sensitivity and specificity of combined CDU
      and BFI results for identification of ICAS were 95% and 99%, respectively. The
      misclassification rates of CDU and BFI were 4.7% and 8.1%, respectively. When
      combined test results were concordant, the misclassification rate decreased to
      1.4%. CONCLUSION: CDU showed a slightly better accuracy than did BFI in the
      diagnosis of carotid artery stenosis. Combined use of CDU and BFI is more
      accurate than use of either test alone.

PMID- 15569765
TI  - Diffusion-weighted imaging of thromboembolic events associated with coil
      embolization of intracranial aneurysms.

PMID- 15569766
TI  - Carotid pseudofenestration: the double-barrel peril.

PMID- 15569767
TI  - Influenza-associated encephalitis-encephalopathy with a reversible lesion in the
      splenium of the corpus callosum: case report and literature review.

PMID- 15569768
TI  - Abnormal fluid-attenuated inversion recovery signal foci in the splenium of a
      patient with presenilin-1 mutation.

PMID- 15569769
TI  - Enlarging vertebral pneumatocysts in the cervical spine.

PMID- 15569770
TI  - Selective IgG2 deficiency due to a point mutation causing abnormal splicing of
      the Cgamma2 gene.
AB  - The mechanism underlying selective IgG subclass deficiency is largely unknown in
      humans. We have previously reported the acquisition of a complete IgG2 deficiency
      in a leukemia patient after bone marrow transplantation. Southern blot analysis
      showed a deletion including the Cgamma2 and Cgamma4 genes on one chromosome in
      the donor, suggesting that the remaining Cgamma2 gene allele was silent. In the
      patient and his two IgG2 deficient brothers, the silent Cgamma2 gene showed both
      germ-line transcription and switch recombination and no structural defects were
      found in the intronic promoter or the switch region of the gene. However, an A-
      >G transition in the fourth nucleotide in the 5' portion of intron 1 was
      identified. Transfection of artificial constructs into the human B cell lines
      demonstrated that this A-->G transition inactivated the normal splice site, and
      instead, a cryptic splice site in the CH1 exon was used in RNA post
      transcriptional processing, leading to a 16 bp deletion of the gamma2 CH1 exon.
      This aberrantly spliced RNA that is mostly derived from germ-line transcription
      in vivo was also detected in both homozygous and heterozygous individuals
      carrying this mutation. These findings suggest a novel genetic mechanism as the
      cause of IgG subclass deficiency in selected patients.

PMID- 15569771
TI  - Release kinetics and cell trafficking in relation to bacterial growth explain the
      time course of blood neutrophils and monocytes during primary Salmonella
      infection.
AB  - Granulocytes and neutrophils are predominantly responding cells during the early
      phase of infection of rats with Salmonella. We propose mathematical and
      experimental models of the kinetics of neutrophil and monocyte responses in
      Salmonella infection via the oral route. Using the models, we estimate that
      approximately 1 in 500 inoculated Salmonella cells actually infected the rat and
      multiplied with a doubling time of 5 h in Peyer's patches, reaching a maximum of
      approximately 10(6) c.f.u./g. In low-dose infection, neutrophil and monocyte
      responses are delayed, but further resemble the responses in high-dose infection.
      Important processes influencing neutrophil and monocyte recruitment are: massive
      migration into the infected tissue, and non-linear release kinetics of
      neutrophils and monocytes from the bone marrow. In conclusion, we can predict
      time series of neutrophil and monocyte responses in low-dose and high-dose
      experimental infection via the oral route.

PMID- 15569772
TI  - The capacity of the natural ligands for CD28 to drive IL-4 expression in naive
      and antigen-primed CD4+ and CD8+ T cells.
AB  - The B7/CD28 costimulatory pathway plays a critical role in T cell activation
      including Th1/Th2 differentiation. However, little is known about whether CD28
      costimulation favors polarization of either Th1 and Th2 or both. Here, we show a
      critical role of the natural ligands for CD28 molecules (B7.2-Ig or B7.1-Ig
      fusion proteins), particularly in the induction of type 2 T cell polarization.
      Upon TCR-triggering with suboptimal doses of anti-CD3, costimulation of naive
      CD4+ T cells with anti-CD28 mAb or B7-Ig fusion proteins led to comparable levels
      of IFN-gamma production. Naive T cells could produce IL-4 when CD28 costimulation
      was done with B7-Ig, but not with anti-CD28. IL-4-selective upregulation was also
      observed when T cells from anti-OVA TCR transgenic mice were stimulated with OVA
      in the presence of B7-Ig. Correlating with IL-4 expression, GATA-3 expression was
      induced much more potently by costimulation with B7-Ig than with anti-CD28 mAb,
      while T-bet induction by these two costimulatory reagents was comparable. This B7
      effect was also applied for naive and antigen-primed CD8+ T cells: IL-4
      expressing CD8+ T cells were generated when naive and alloantigen-primed T cells
      were stimulated with anti-CD3 and recall antigens, respectively, in the presence
      of B7-Ig costimulation. Importantly, such CD8+ T cell differentiation required
      the coexistence of CD4+ T cells during the initial TCR stimulation. These
      observations indicate that both type 2 CD4 and CD8 T cell polarizations are
      efficiently induced via costimulation of CD28 with its natural ligands, although
      the differentiation of CD8+ T cells is dependent on CD4+ cells.

PMID- 15569773
TI  - Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory
      effect on degranulation from basophilic leukemia RBL-2H3.
AB  - Mast cells and basophils express the high affinity receptor for IgE (FcepsilonRI)
      and play a central role for IgE-associated immediate hypersensitivity reactions
      and allergic disorders. Cross-linking of FcepsilonRI-bound IgE with multivalent
      antigen initiates the activation of mast cells and basophils, resulting in the
      degranulation from these cells. We have recently identified a novel inhibitory
      receptor, myeloid-associated immunoglobulin-like receptor (MAIR)-I, which is
      expressed on mast cells as well as other myeloid cell lineages. Co-ligation of
      FcepsilonRI and MAIR-I inhibits IgE-mediated degranulation from mast cells.
      However, MAIR-I-mediated signaling pathways involved in the inhibition remain
      undetermined. Here, we demonstrate that the transfectant of rat basophil leukemia
      RBL-2H3 expressing wild-type MAIR-I is tyrosine phosphorylated and recruits SHP-1
      and SHIP upon cross-linking of MAIR-I. By using RBL-2H3 transfectants expressing
      variable mutant MAIR-I at Y233, Y258, Y270 and/or Y299, we further demonstrate
      that both Y258 and Y270, but not Y233 and Y299, were phosphorylated and were
      essentially required for inhibition of IgE-mediated degranulation from the RBL
      2H3 transfectant.

PMID- 15569774
TI  - Pregnancy-induced alterations of B cell maturation and survival are
      differentially affected by Fas and Bcl-2, independently of BcR expression.
AB  - In the present work, we have analyzed the roles of two molecules involved in the
      regulation of cell survival, Bcl2 and Fas, in the pregnancy-induced down
      regulation of B lymphopoiesis in mice. Our results show that the overexpression
      of the anti-apoptotic molecule Bcl2 in Bcl2-transgenic (Tg) B cells is able to
      protect 'D' fraction pre-B cells from pregnancy-induced deletion. In contrast, in
      Fas(lpr/lpr) mice bearing a mutated cell death receptor Fas, such B cell targets
      are not protected. Moreover, bone marrow B cell sub-populations at both ends of
      the differentiation pathway, i.e. pre-pro 'A' and mature 'E-F' fraction B cells,
      which are not the major targets of the pregnancy-induced down-regulation, are
      doubled during pregnancy in Fas(lpr/lpr) mice only. Altogether, these data
      strongly suggest that B cell down-regulation during pregnancy is due to apoptotic
      events blocked by Bcl2, but does not depend on a functional Fas receptor. The
      expression of a transgenic BcR in the 3-83mudelta BcR-Tg mouse model yields
      similar observations, which indicates that early BcR expression does not alter
      bone marrow B cell fates during pregnancy.

PMID- 15569775
TI  - Neuroprotective effects of (-)-epigallocatechin gallate following hypoxia
      ischemia-induced brain damage: novel mechanisms of action.
AB  - (-)-Epigallocatechin gallate (EGCG) is a potent antioxidant that is
      neuroprotective against ischemia-induced brain damage. However, the
      neuroprotective effects and possible mechanisms of action of EGCG after hypoxia
      ischemia (HI) have not been investigated. Therefore, we used a modified "Levine"
      model of HI to determine the effects of EGCG. Wistar rats were treated with
      either 0.9% saline or 50 mg/kg EGCG daily for 1 day and 1 h before HI induction
      and for a further 2 days post-HI. At 26-days-old, both groups underwent permanent
      left common carotid artery occlusion and exposure to 8% oxygen/92% nitrogen
      atmosphere for 1 h. Histological assessment showed that EGCG significantly
      reduced infarct volume (38.0+/-16.4 mm(3)) in comparison to HI + saline (99.6+/
      15.6 mm(3)). In addition, EGCG significantly reduced total (622.6+/-85.8 pmol L
      [(3)H]citrulline/30 min/mg protein) and inducible nitric oxide synthase (iNOS)
      activity (143.2+/-77.3 pmol L-[(3)H]citrulline/30 min/mg protein) in comparison
      to HI+saline controls (996.6+/-113.6 and 329.7+/-59.6 pmol L-[(3)H]citrulline/30
      min/mg protein for total NOS and iNOS activity, respectively). Western blot
      analysis demonstrated that iNOS protein expression was also reduced. In contrast,
      EGCG significantly increased endothelial and neuronal NOS protein expression
      compared with HI controls. EGCG also significantly preserved mitochondrial
      energetics (complex I-V) and citrate synthase activity. This study demonstrates
      that the neuroprotective effects of EGCG are, in part, due to modulation of NOS
      isoforms and preservation of mitochondrial complex activity and integrity. We
      therefore conclude that the in vivo neuroprotective effects of EGCG are not
      exclusively due to its antioxidant effects but involve more complex signal
      transduction mechanisms.

PMID- 15569776
TI  - Oxidative stress in atherosclerosis-prone mouse is due to low antioxidant
      capacity of mitochondria.
AB  - Atherosclerotic disease remains a leading cause of death in westernized
      societies, and reactive oxygen species (ROS) play a pivotal role in
      atherogenesis. Mitochondria are the main intracellular sites of ROS generation
      and are also targets for oxidative damage. Here, we show that mitochondria from
      atherosclerosis-prone, hypercholesterolemic low-density lipoprotein (LDL)
      receptor knockout mice have oxidative phosphorylation efficiency similar to that
      from control mice but have a higher net production of ROS and susceptibility to
      develop membrane permeability transition. Increased ROS production was observed
      in mitochondria isolated from several tissues, including liver, heart, and brain,
      and in intact mononuclear cells from spleen. In contrast to control mitochondria,
      knockout mouse mitochondria did not sustain a reduced state of matrix NADPH, the
      main source of antioxidant defense against ROS. Experiments in vivo showed faster
      liver secretion rates and de novo synthesis of triglycerides and cholesterol in
      knockout than in control mice, suggesting that increased lipogenesis depleted the
      reducing equivalents from NADPH and generated a state of oxidative stress in
      hypercholesterolemic knockout mice. These data provide the first evidence of how
      oxidative stress is generated in LDL receptor defective cells and could explain
      the increased LDL oxidation, cell death, and atherogenesis seen in familiar
      hypercholesterolemia.

PMID- 15569777
TI  - Adherence to a six-dose regimen of artemether-lumefantrine for treatment of
      uncomplicated Plasmodium falciparum malaria in Uganda.
AB  - Measuring baseline levels of adherence and identifying risk factors for non
      adherence are important steps before the introduction of new antimalarials. In
      Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine
      (Coartem) in its latest World Health Organization blister formulation. Patients
      with uncomplicated Plasmodium falciparum malaria were prescribed artemether
      lumefantrine and received an explanation of how to take the following five doses
      at home. A tablet count was made and a questionnaire was completed during a home
      visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non
      adherent, whereas 189 (90.0%) were probably adherent. Age group was not
      associated with adherence. Lack of formal education was the only factor
      associated with non-adherence after controlling for confounders (odds ratio =
      3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were
      lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among
      adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this
      difference was not statistically significant. The high adherence to artemether
      lumefantrine found in our study suggest that this drug is likely to be very
      effective in Mbarara provided that patients receive clear dosage explanations.

PMID- 15569778
TI  - The impact of age, temperature, and parasite density on treatment outcomes from
      antimalarial clinical trials in Kampala, Uganda.
AB  - Antimalarial drug treatment policy in sub-Saharan Africa is generally guided by
      the results of clinical drug efficacy studies in patients with uncomplicated
      Plasmodium falciparum malaria. The selection criteria used to enroll these
      patients often vary and may have a significant impact on treatment outcomes. In
      Kampala, Uganda, we investigated the impact of age, baseline temperature, and pre
      treatment parasite density on estimates of treatment efficacy using a statistical
      modeling approach in 2,138 patients enrolled in six clinical trials involving
      seven different treatment regimens. Decreasing age, increasing temperature, and
      increasing parasite density were all independent predictors of an increased risk
      of treatment failure across all treatment groups. Compared with an unrestrictive
      approach to subject selection, enrolling only patients fulfilling selection
      criteria recommended by the World Health Organization (age < 5 years old,
      documented fever, and parasite density < 200,000/microL) increased the risk of
      treatment failure by 25-60% for the different treatment regimens. Caution should
      be taken when comparing results from drug efficacy studies with different subject
      selection criteria.

PMID- 15569779
TI  - Comparison of the parasitologic efficacy of amodiaquine and sulfadoxine
      pyrimethamine in the treatment of Plasmodium falciparum malaria in the Bungoma
      District of western Kenya.
AB  - The efficacy of amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) was assessed
      in 310 symptomatic children from western Kenya with uncomplicated Plasmodium
      falciparum malaria. A non-blinded, randomized, 14-day study was performed and
      parasitologic criteria were used. Of 310 patients included, 238 (77%) completed
      the study: 120 received AQ and 118 received SP. In those treated with AQ, there
      were sensitive (S) infections in 107 patients (89.2%, 95% confidence interval
      [CI] = 82.2, 94.1%), RI resistance in 10 (8.3%, 95% CI = 4.1, 14.8%), RII
      resistance in 1 (0.8%, 95% CI = 0, 4.6%), and RIII resistance in 2 (1.7%, 95% CI
      = 0.2, 5.9%). In those treated with SP, there were S infections in 74 patients
      (62.7%, 95% CI = 53.3, 71.4%), RI resistance in 21 (17.8%, 95% CI = 11.4, 25.9%),
      RII resistance in 11 (9.3%, 95% CI = 4.7, 16.1%), and RIII resistance in 12
      (10.2%, 95% CI = 5.4, 17.1%). Resistance rates were consistently higher in the SP
      treated patients (P < 0.001). Resistance to SP in this area has reached such
      levels that it should no longer be the first-line treatment. Alternative
      treatment, such as SP plus AQ combination treatment or artemisinin combination
      treatment, is urgently needed.

PMID- 15569780
TI  - Cerebral metabolic reduction in severe malaria: fluorodeoxyglucose-positron
      emission tomography imaging in a primate model of severe human malaria with
      cerebral involvement.
AB  - Cerebral metabolic changes in Japanese macaques (Macaca fuscata) infected with
      Plasmodium coatneyi, a primate model of severe human malaria with cerebral
      involvement, were directly evaluated by fluorodeoxyglucose-positron emission
      tomography (FDG-PET). We observed diffuse and heterogeneous reduction of
      metabolism in the cerebral cortex in the acute phase of malaria infection.
      Neuropathologic examination showed preferential sequestration of parasitized red
      blood cells in the cerebral microvasculature. However, hemorrhagic change or
      necrosis was not observed in hematoxylin and eosin-stained and Nissl-stained
      brain tissues. This suggests that reduction of cerebral metabolism occurs before
      parenchymal changes appear in the brain. This may be one reason why more than
      half of the patients with cerebral malaria have no neurologic sequelae after
      recovery.

PMID- 15569781
TI  - Rapid detection of malaria infection in vivo by laser desorption mass
      spectrometry.
AB  - Rapid diagnosis leading to effective treatment is essential to control escalating
      infectious diseases such as malaria. Malaria pigment (hemozoin) detection by
      laser desorption mass spectometry (LDMS) was recently shown to be a sensitive
      (<10 parasites/muL) technique for detecting Plasmodium falciparum parasites
      cultured in human blood. To examine the use of LDMS in a rapid new malaria
      screening assay, we followed the time course of P. yoelii infections in mice in
      parallel with light microscopy and a colorimetric hemozoin assay. Hemozoin was
      detected by LDMS in 0.3 muL of blood within two days of infection independently
      of the inoculating dose of 10(6), 10(4), or 10(2) parasite-infected erythrocytes.
      Microscopy and colorimetric hemozoin determinations lagged the LDMS detection of
      infections by 2-4 and 3-5 days, respectively, except at the highest inoculation
      dose. The LDMS detection of hemozoin is a potentially more rapid screen than
      light microscopy for detecting malaria infection in this mouse model at
      parasitemias <0.1%.

PMID- 15569782
TI  - Symptoms of intestinal schistosomiasis presenting during treatment of large B
      cell lymphoma.
AB  - We report a case of chronic intestinal schistosomiasis presenting in a previously
      asymptomatic 34-year-old woman from Saudi Arabia with large B cell lymphoma. The
      patient presented with abdominal pain, constipation, recurrent rectal bleeding,
      and persistent mild eosinophilia during chemotherapy. Stools were repeatedly
      negative for parasite ova, but duodenal and colonic biopsies demonstrated
      Schistosoma eggs and eosinophilic granulomatous inflammation. Immunosuppressed
      patients with schistosomiasis may have diminished egg excretion. Diagnosis
      requires a high index of suspicion since stool test results may be negative and
      intestinal biopsies may be needed to make the diagnosis.

PMID- 15569783
TI  - Spatial and temporal variability in schistosome cercarial density detected by
      mouse bioassays in village irrigation ditches in Sichuan, China.
AB  - A mouse bioassay was used monthly over the infection season of 2001 to determine
      the temporal and spatial variability of schistosome cercarial density in
      irrigation ditches in five villages in southwestern Sichuan Province in the
      People's Republic of China. Analysis of variance showed that approximately half
      of the variability was due to the village and site within the village, with
      little contribution from air temperature, weekly average rainfall, or the month
      within the infection season in which the bioassay was performed. The location
      specific variability in these data suggest that epidemiologic studies will
      generally have low power to detect the influence of water-contact intensity on
      human parasite burden without taking account of variations in cercarial density
      at sites of water contact.

PMID- 15569784
TI  - Disseminated cutaneous leishmaniasis due to Leishmania guyanensis: case of a
      patient with 425 lesions.
AB  - Disseminated cutaneous leishmaniasis is characterized by the presence of a large
      (> or =10) number of lesions at several anatomic sites (head, limbs, and trunk).
      Most of the lesions are small, papular, and appear simultaneously with or
      secondarily to one or several ulcerated lesions of localized cutaneous
      leishmaniasis. We report the first case of disseminated cutaneous leishmaniasis
      in French Guiana. It concerns a 24-year-old woman who tested negative for human
      immunodeficiency virus (HIV). The disease began with three lesions that became
      ulcerated. One week later, multiple papulo-nodular lesions appeared. We counted a
      total of 425 lesions. Leishmania were observed in the lesions. The species
      involved was L. guyanensis, which has never been described in a case of
      disseminated cutaneous leishmaniasis. The patient was rapidly cured by a single
      course of pentamidine. Disseminated cutaneous leishmaniasis should be
      distinguished from other types of leishmaniasis with multiple lesions. These
      include anergic diffuse cutaneous leishmaniasis, post-kala-azar leishmaniasis,
      and leishmaniasis associated with HIV infection.

PMID- 15569785
TI  - Elevated plasma levels of interferon (IFN)-gamma, IFN-gamma inducing cytokines,
      and IFN-gamma inducible CXC chemokines in visceral leishmaniasis.
AB  - Interferon (IFN)- gamma plays an important role during immune responses against
      leishmaniasis. Production of IFN-gamma is regulated by interleukin (IL)-12, IL
      18, and IL-15. Interferon-gamma-inducible protein (IP)-10 and monokine induced by
      IFN-gamma (Mig) are CXC chemokines, the production of which, at least in part, is
      IFN-gamma dependent. A follow-up study of individuals infected with Leishmania
      donovani was undertaken in an area of Ethiopia endemic for visceral leishmaniasis
      (VL). Plasma levels of IFN-gamma, IL-12p40, IL-18, IL-15, IP-10, and Mig were
      markedly elevated in symptomatic VL patients (n = 70) compared with individuals
      with asymptomatic Leishmania infections (n = 39), malaria patients (n = 13), and
      healthy controls from the endemic area (n = 12). A significant decrease of IFN
      gamma and all mediators was observed after treatment of VL patients (n = 33).
      These data show that increased plasma levels of IFN-gamma, as well as the
      mediators involved in the production and the activity of this cytokine, are
      characteristic of active VL in humans, and may play an important immunopathogenic
      role. The data also suggest that in patients with VL, the production of type 1
      cytokines is not depressed, but there appears to be an unresponsiveness to the
      stimuli of type 1 cytokines. The underlying causes of immunologic
      unresponsiveness remain a subject of further investigation.

PMID- 15569786
TI  - Characterization of the early cellular immune response to Leishmania major using
      peripheral blood mononuclear cells from Leishmania-naive humans.
AB  - While the response to Leishmania major is well characterized in mice, there is
      much less known about the human immune response, particularly early after
      exposure to the parasite. Therefore, we developed a primary in vitro (PIV) system
      that allowed us to address these questions. We co-cultured peripheral blood
      mononuclear cells from Leishmania-naive donors with L. major parasites and found
      that the responding PIV cells produced interferon-gamma and interleukin-12 (IL
      12). When restimulated, these PIV cells also occasionally produced IL-5. Both CD4
      and CD8 cells and both HLA class I and II cell activation pathways appeared to
      play a role in the PIV system, and cell activation was dependent upon the
      presence of antigen-presenting cells. Moreover, PIV cells generated with L. major
      showed considerable cross-reactivity with other species of Leishmania. Finally,
      the PIV cells augmented intracellular killing of L. major when they were co
      cultured with macrophages infected with the parasite.

PMID- 15569787
TI  - Comparison of generic to branded pentavalent antimony for treatment of new world
      cutaneous leishmaniasis.
AB  - The cost of generic pentavalent antimony (generic stibogluconate) is
      approximately one-sixth that of branded pentavalent antimony (stibogluconate in
      the form of Pentostam or meglumine antimoniate in the form of Glucantime. We
      compared generic stibogluconate to Pentostam and Glucantime for the treatment of
      cutaneous leishmaniasis patients in Bolivia and Colombia. For all 114 patients,
      the per-protocol cure rates were 83-91% and the intent-to-treat cure rates were
      75-83%. The highest values were in the generic stibogluconate group. The
      incidence of pancreatic enzyme abnormalities was 48-88% and the incidence of
      liver enzyme abnormalities was 48-87%. The lowest incidences were in the generic
      stibogluconate group. The efficacy and tolerance of inexpensive generic
      stibogluconate appears comparable to branded formulations for the treatment of
      cutaneous leishmaniasis in these endemic regions.

PMID- 15569788
TI  - Epidemiologic and environmental investigation of a recreational water outbreak
      caused by two genotypes of Cryptosporidium parvum in Ohio in 2000.
AB  - In August 2000, the Ohio Department of Health requested assistance to investigate
      a cryptosporidiosis outbreak with more than 700 clinical case-patients. An
      epidemiologic and environmental investigation was conducted. Stool specimens,
      pool water, and sand filter samples were analyzed. A community-based case-control
      study showed that the main risk factor was swimming in pool A (odds ratio [OR] =
      42, 95% confidence interval [CI] = 12.3-144.9). This was supported by results of
      polymerase chain reaction (PCR) analysis, which showed the presence of both the
      human and bovine genotypes of Cryptosporidium parvum in case-patients and samples
      from the filter of pool A. A pool-based case-control study indicated that the
      highest risk was related to exposure to pool water via the mouth (OR = 5.1, 95%
      CI = 2.1-12.5) or to pool sprinklers (OR = 2.5, 95% CI = 1.3-4.7). Fecal
      accidents at the pool were documented. Records indicated that the pool met local
      health regulations. The outbreak, caused by co-infection with two C. parvum
      genotypes (human and bovine), underscores the need for concerted action to
      improve public health policies for recreational water facilities and enhanced
      education regarding the potential for disease transmission through pools.

PMID- 15569789
TI  - Chagas disease in rural areas of Chaco Province, Argentina: epidemiologic survey
      in humans, reservoirs, and vectors.
AB  - We studied the seroprevalence of antibodies against Trypanosoma cruzi in the
      human population along with domiciliary infestation by triatomine bugs in an area
      endemic for Chagas disease in the Chaco Province of Argentina. In addition, we
      carried out parasitologic surveys in patients, dogs, wild mammals, and vectors.
      The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261)
      in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%,
      with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs
      and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10%
      (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies,
      our data suggest that 1) there are zones requiring immediate sanitary action, and
      2) nationwide estimates are based on very heterogeneous epidemiologic situations.
      This heterogeneity emphasizes the importance of in-depth studies of restricted
      areas to provide additional information for a better understanding of the present
      status of Chagas disease in Argentina.

PMID- 15569790
TI  - Short report: benznidazole efficacy among Trypanosoma cruzi-infected adolescents
      after a six-year follow-up.
AB  - Data from a six-year follow-up of Trypanosoma cruzi-infected adolescents enrolled
      in a randomized, double-blind, clinical trial of benznidazole showed successful
      chemotherapy in 64.7% (95% confidence interval [CI] = 50.2-78.7) and 84.7% (95%
      CI = 66.8-92.9), respectively, by intention-to treat and by per protocol analysis
      measured by seronegativity in a chemiluminescent enzyme-linked immunosorbent
      assay with a purified trypomastigote mucin antigen. No incident case of
      cardiomyopathy was detected by electrocardiogram assessment in this cohort of
      adolescents who had been infected in childhood. The persistent and consistently
      long-term negative serologic reactions suggest the absence of the parasite in the
      treated patients and reinforces the recommendation of early benznidazole
      chemotherapy for T. cruzi-infected infants as a public health policy in endemic
      areas.

PMID- 15569791
TI  - Geographic distribution of lymphatic filariasis in Haiti.
AB  - Although lymphatic filariasis is known to have been endemic in Haiti since at
      least the mid 1700s, a national filariasis survey has never been conducted. As a
      first step in the national program to eliminate filariasis, we collected blood in
      January-April 2001 from 50-250 school children (6-11 years old) in all 133
      communes of the country using an adaptation of the lot quality assurance sampling
      method. Of 22,365 children tested, 901 (4.0%) were positive for circulating
      Wuchereria bancrofti antigen. When weighted by commune population, the overall
      national antigen prevalence in this age group was 7.3%. Infected children were
      found in 117 (87.9%) communes, the most heavily affected areas being concentrated
      in the northern part of the country. In only 16 (12.1%) communes were all 250
      children antigen negative. Thus, W. bancrofti infection in Haiti is much more
      widespread than previously realized; virtually the entire population of the
      country may be considered at risk of infection.

PMID- 15569792
TI  - The effects of long-term community level treatment with ivermectin (Mectizan) on
      adult Onchocerca volvulus in Latin America.
AB  - The objective of this study was to examine nodules from Mexico, Guatemala, and
      Ecuador collected over a one-year period (2001) to determine the effects of semi
      annual ivermectin treatments on Onchocerca volvulus macrofilarial populations.
      Nodules were sectioned, stained with hematoxylin and eosin, and histologic
      findings were compared between countries and with historical data prior to the
      introduction of ivermectin into the region. Nodules from Ecuador had 10 times
      more dead or moribund worms than the historical control (66.6% versus 6.5%);
      nodules from patients from Mexico and Guatemala did not differ from the control.
      More than 80% of the female worms in each country were uninseminated and
      producing unfertilized oocytes. Nodules containing males differed in each country
      from the historical control (P < 0.0001), with presence of males ranging from
      19.7% in Mexico to 13.6% in Ecuador versus 73% in the control. Nodules with
      females producing active microfilariae ranged from 7.8% (Mexico) to 2.7%
      (Ecuador) versus 60% in the historical control (P < 0.0001). Nodules from Ecuador
      and Mexico were significantly smaller in size than those from Guatemala or
      historical controls (P < 0.0005). These results depict a deteriorating condition
      of adult O. volvulus populations in Mexico, Guatemala and Ecuador, indicating
      that semi-annual ivermectin treatment of >/=6 years has had a profound effect on
      survival and reproduction of this species.

PMID- 15569793
TI  - An in vitro larval motility assay to determine anthelmintic sensitivity for human
      hookworm and Strongyloides species.
AB  - With the implementation of programs to control lymphatic filariasis and soil
      transmitted helminths using broad spectrum anthelmintics, including albendazole
      and ivermectin, there is a need to develop an in vitro assay for detection of
      drug resistance. This report describes an in vitro assay for measuring the
      effects of ivermectin and benzimidazoles on the motility of larvae of the
      hookworm species Ancylostoma ceylanicum, A. caninum, and Necator americanus, and
      Strongyloides species including Strongyloides stercoralis, and S. ratti. A dose
      response relationship was demonstrated with each of the parasite species, with
      distinct differences observed between the various species. In pilot field testing
      of the assay with N. americanus larvae recovered from human fecal samples, a dose
      response relationship was observed with ivermectin. While the assay has
      demonstrated the ability to determine drug responsiveness, its usefulness in
      resistance detection will require correlation with the clinical outcome among
      individuals infected with parasite strains showing different drug sensitivities.

PMID- 15569794
TI  - Prevalence of Heterophyes nocens and Pygydiopsis summa infections among residents
      of the western and southern coastal islands of the Republic of Korea.
AB  - To determine the distribution and prevalence of heterophyid fluke infections on
      coastal islands of the Republic of Korea, fecal specimens were collected from
      4,179 people residing on 45 islands in the West (Yellow) and South Seas and
      examined using the formalin-ether and Kato-Katz techniques. Eggs of Heterophyes
      nocens were found in 459 (11.0%) residents of 42 islands, with an average number
      of eggs per gram (epg) of feces of 79.6. Eggs of Pygidiopsis summa were found in
      49 (1.2%) on 12 islands, with an average epg of 253.0. The egg-positive rate for
      H. nocens was the highest on Chungdo (32.6%), followed by Imchado (27.3%); P.
      summa was most prevalent on Imchado (15.2%). The majority (78.9% [362 of 549] of
      those infected with H. nocens and 81.6% [40 of 49] of those infected with P.
      summa) of those infected were adults more than 40 years old. Adult flukes of
      these species were recovered from residents of Imchado by treatment with
      praziquantel and purgation. Our results indicate that H. nocens and P. summa are
      indigenous to the southern and western coastal islands of the Republic of Korea.

PMID- 15569795
TI  - Treatment of cutaneous gnathostomiasis with ivermectin.
AB  - In a randomized open study, we compared the efficacy of a single dose of oral
      ivermectin (200 microg/kg) and oral albendazole (400 mg/day for 21 days) for the
      treatment of cutaneous gnathostomiasis. Thirty-one patients were randomly
      assigned to receive ivermectin (n = 17) or albendazole (n = 14). Thirteen of 17
      patients who received ivermectin responded, 3 relapsed, and 1 was unresponsive
      (cure rate = 76%). Thirteen of 14 patients who received albendazole responded
      very well and did not relapse. Only one patient was unresponsive (cure rate =
      92%; P > 0.05). No major side effects were observed in both groups. We concluded
      that a single dose of ivermectin (200 microg/kg) is less effective than
      albendazole (400 mg/day for 21 days) for treatment of cutaneous gnathostomiasis,
      but there was no statistically significant difference (P > 0.05).

PMID- 15569796
TI  - Spatial-temporal analysis of Ross River virus disease patterns in Queensland,
      Australia.
AB  - Ross River virus is the most common vector-borne disease in Australia, with the
      majority of notifications being in Queensland. This study describes a
      retrospective spatial analysis of Queensland Ross River virus disease
      notifications spanning a 10-year period. Notifications were mapped to the local
      government area (LGA) of the residence of the patient. Ross River virus disease
      outbreaks within each LGA were detected by applying a Poisson model. Estimates of
      the seasonal incidence rates indicated wide variation between seasons and LGAs.
      Positive spatial autocorrelation between LGAs experiencing outbreaks indicated
      that LGAs within the same region often experience outbreaks at the same time. A
      hierarchical cluster analysis of the outbreak data was used to group LGAs with
      similar temporal outbreak patterns. This analysis highlights the variability in
      Ross River virus disease notification rates across Queensland, and provides a
      robust method for identifying disease outbreaks.

PMID- 15569797
TI  - Short report: detection probability of arbovirus infection in mosquito
      populations.
AB  - An important component of arbovirus surveillance is monitoring the vector for
      presence of the pathogen. Intervention and preventive programs need early
      detection of arboviral activity in mosquito populations. In this report, we
      examine the factors affecting the probability of detection of mosquito
      infections. Since arbovirus infection rates in mosquito populations are very low,
      observations of zero-infected mosquito samples are common. Using statistical
      models, we describe methods to estimate the probability of detection and upper
      bounds of confidence intervals of mosquito infection rates as measures of
      confidence for observations of zero infection. Our results show that detection of
      low levels of mosquito infections requires large samples (greater than 1,600
      individuals) for a high probability (0.8) of detection. Due to focal transmission
      of arboviruses, grouping samples over different sampling sites and times is often
      inappropriate for detection of mosquito infection. We emphasize sample size as a
      key determinant in detection of mosquito infections and recommend intensified
      entomologic surveys at sentinel sites to detect arboviral activity.

PMID- 15569798
TI  - Construction of yellow fever/St. Louis encephalitis chimeric virus and the use of
      chimeras as a diagnostic tool.
AB  - St. Louis encephalitis (SLE) and West Nile (WN) flaviviruses are genetically
      closely related and cocirculate in the United States. Virus neutralization tests
      provide the most specific means for serodiagnosis of infections with these
      viruses. However, use of wild-type SLE and WN viral strains for laboratory
      testing is constrained by the biocontainment requirements. We constructed two
      highly attenuated yellow fever (YF) virus chimeras that contain the premembrane
      envelope (prM-E) protein genes from the virulent MSI-7 (isolated in the United
      States) or the naturally attenuated CorAn9124 (Argentina) SLE strains. The YF/SLE
      (CorAn version) virus and the previously constructed YF/WN chimera were shown to
      specifically distinguish between confirmed human SLE and WN cases in a virus
      neutralization test using patient sera. These chimeras have the potential for use
      as diagnostic reagents and vaccines against SLE and WN.

PMID- 15569799
TI  - Household survey of dengue infection in central Brazil: spatial point pattern
      analysis and risk factors assessment.
AB  - Urban dengue fever is now considered a major public health threat in most
      American countries. A household survey was conducted in the city of Goiania in
      central Brazil in 2001 to assess prevalence of dengue infection and individual
      and area-based risk factors. Spatial point pattern analysis was performed using
      the dual Kernel method. A total of 1,610 households were surveyed; 1,585
      individuals more than five years old had blood and data collected. Sera were
      tested for IgM/IgG antibodies by an enzyme-linked immunoassay. Area-based
      indicators derived from census data were linked to geocoded residential address.
      The seroprevalence of dengue was 29.5% and the estimate prevalence surface
      reached 50% in the outskirts areas. The risk of infection was significantly
      associated with older age (P < 0.01), low education (odds ratio [OR] = 3.45, 95%
      confidence interval [CI] = 1.82-6.55), and low income (OR = 1.32, 95% CI = 1.02
      1.71) in multivariate analysis. This study highlighted the heterogeneity of
      dengue transmission within the city and can assist in spatial targeting control
      interventions.

PMID- 15569800
TI  - Oxidative stress in adult dengue patients.
AB  - An association between viral diseases and increased oxidative stress has been
      suggested. The time course of serum levels of total antioxidant status (TAS),
      peroxidation potential (PP), glutathione (GSH), lipid peroxidation measured as
      hydroperoxides, and malondyaldehyde and 4-hydroxyalkenals (MDA + 4-HDA), as well
      as antioxidant enzymatic activity of superoxide dismutase (SOD) and glutathione
      peroxidase (GPx), were measured in 22 serologically confirmed dengue patients.
      Most of the patients had dengue fever and three of them had dengue hemorrhagic
      fever. The redox parameters were compared with those of age- and sex- matched
      controls. No significant difference was observed for levels of GSH and TAS
      between patients and controls. Levels of PP, MDA + 4-HDA, and SOD were
      significantly higher. Levels of GPx and total hydroperoxides were significantly
      lower in patients in comparison with controls. These findings suggest that the
      alteration in redox status could result of increased oxidative stress and it may
      play a role in the pathogenesis of the disease.

PMID- 15569801
TI  - Hantavirus pulmonary syndrome in northwestern Argentina: circulation of Laguna
      Negra virus associated with Calomys callosus.
AB  - The purpose of this study was to characterize the hantaviruses circulating in
      northwestern Argentina. Human and rodent studies were conducted in Yuto, where
      most cases of hantavirus pulmonary syndrome (HPS) occur. Partial virus genome
      sequences were obtained from the blood of 12 cases of HPS, and from the lungs of
      4 Calomys callosus and 1 Akodon simulator. Phylogenetic analysis showed that
      three genotypes associated with HPS circulate in Yuto. Laguna Negra (LN) virus,
      associated with C. laucha in Paraguay, was identified for the first time in
      Argentina; it was recovered from human cases and from C. callosus samples. The
      high sequence identity between human and rodent samples implicated C. callosus as
      the primary rodent reservoir for LN virus in Yuto. The genetic analysis showed
      that the Argentinian LN virus variant differed 16.8% at the nucleotide level and
      2.9% at the protein level relative to the Paraguayan LN virus. The other two
      hantavirus lineages identified were the previously known Bermejo and Oran
      viruses.

PMID- 15569802
TI  - Trigger events: enviroclimatic coupling of Ebola hemorrhagic fever outbreaks.
AB  - We use spatially continuous satellite data as a correlate of precipitation within
      tropical Africa and show that the majority of documented Ebola hemorrhagic fever
      outbreaks were closely associated with sharply drier conditions at the end of the
      rainy season. We propose that these trigger events may enhance transmission of
      Ebola virus from its cryptic reservoir to humans. These findings suggest specific
      directions to help understand the sylvatic cycle of the virus and may provide
      early warning tools to detect possible future outbreaks of this enigmatic
      disease.

PMID- 15569803
TI  - Age-wise exposure rates to hepatitis e virus in a southern Indian patient
      population without liver disease.
AB  - To determine the age-stratified exposure to hepatitis E virus (HEV) in patients
      attending a tertiary care hospital in southern India, serum samples from 600
      individuals were tested using a commercial HEV IgG enzyme-linked immunosorbent
      assay. Subjects were composed of blood donors, antenatal women, and pre-operative
      individuals who were negative for hepatitis B surface antigen and antibody to
      hepatitis C virus with no evidence of liver disease; 200 each were 1-5 and 6-15
      years old and 100 each were 16-40 and > or = 41 years old. One (0.5%) sample was
      positive in those 1-5 years old, two (1.0%) in those 6-15 years old, eight (8%)
      in those 16-40 years old, and 13 (13%) in those > or = 41 years old. The overall
      seropositivity rate was 4%. However, there was an age-related increase in
      exposure to HEV that was statistically significant (P < 0.001), with a higher HEV
      seropositivity in urban individuals.

PMID- 15569804
TI  - Human immunodeficiency virus type 1 (HIV-1) and Mycobacterium leprae co
      infection: HIV-1 subtypes and clinical, immunologic, and histopathologic profiles
      in a Brazilian cohort.
AB  - Co-infections with human immunodeficiency virus (HIV) and Mycobacterium leprae
      represent unique opportunities to investigate the interaction of both pathogens.
      We determined the immunologic, virologic, and histopathologic characteristics of
      22 co-infected Brazilian patients (median age = 38 years, 81.8% males, 72.2% with
      paucibacillary leprosy, and 95.4% with acquired immunodeficiency syndrome). The
      HIV-1 subtypes B and BF predominated in envelope and gag heteroduplex mobility
      analysis. Borderline tuberculoid (BT), tuberculoid, lepromatous, and
      indeterminate morphology with CD3+, CD8+, and CD68+ cell distributions compatible
      with leprosy patients not infected with HIV were observed. Histologic evidence of
      nerve damage was observed in BT lesions. IgM antibody to M. leprae-specific
      phenolic glycolipid I was not detected. Two of six co-infected patients monitored
      during highly active antiretroviral therapy (HAART) developed a leprosy type 1
      reaction after an increase in CD4+ cells, suggesting an immune restoration
      phenomenon. Clinical, immunologic, histopathologic, and virologic features among
      these HIV-leprosy co-infected patients indicate that each disease progressed as
      in single infection. However, HAART immune reconstitution may trigger potential
      adverse effects, such as leprosy acute inflammatory episodes.

PMID- 15569805
TI  - Susceptibility of Leptospira serovars to antimalarial agents.
AB  - Leptospirosis has recently been described to cause concomitant infection with
      malaria. Only doxycycline has proven to have chemoprophylactic and therapeutic
      efficacy for both malaria and leptospirosis. To assess whether other traditional
      antimalarial agents have antileptospiral activity, we performed broth
      microdilution susceptibility testing of 16 Leptospira serovars (6 species/14
      serogroups) to various agents. Artemisinin, atovaquone, chloroquine, mefloquine,
      primaquine, proguanil, pyrimethamine, sulfadoxine, quinine, quinidine, and
      combinations of atovaquone/proguanil and pyrimethamine/sulfadoxine all had a 90%
      minimum inhibitory concentration (MIC(90)) > 25 microg/mL (the upper limit of
      testing). The only agents identified with the potential to treat both infections
      other than doxycycline (MIC(90) = 1.56 microg/mL) were azithromycin (MIC(90) =
      0.002 microg/mL) and clindamycin (MIC(90) = 0.2 microg/mL).

PMID- 15569806
TI  - Quantitative biofilm assay using a microtiter plate to screen for
      enteroaggregative Escherichia coli.
AB  - The gold standard for identification of Enteroaggregative Escherichia coli (EAEC)
      remains the HEp-2 cell adherence test, which is time-consuming and requires
      specialized facilities. We evaluated the usefulness of a quantitative biofilm
      assay to screen for EAEC from a total of 1,042 E. coli strains from children with
      diarrhea. Bacteria were incubated overnight in high-glucose Dulbecco's modified
      Eagle's medium using a polystyrene microtiter plate. The plate was stained with
      crystal violet after washing, and the biofilm was quantified using an enzyme
      linked immunosorbent assay plate reader. The aggR gene was evaluated by a
      polymerase chain reaction. Forty-eight (77.4%) of 62 strains with an optical
      density at 570 nm (OD(570)) > 0.2 were identified as EAEC by the HEp-2 adherence
      test, while no EAEC was found in strains with an OD(570) < or = 0.2. Twenty-one
      aggR+ and 27 aggR - EAEC strains could be screened by an OD(570) > 0.2 using this
      assay. Although confirmation by a HEp-2 cell adherence test is needed, this
      biofilm assay is convenient and useful in screening for EAEC.

PMID- 15569807
TI  - Short report: evaluation of a simple and inexpensive photometric device for the
      measurement of hemoglobin.
AB  - We have evaluated the accuracy of a simple and inexpensive photometric device
      (DHT) for the estimation of the blood concentration of hemoglobin by comparison
      with an automated, high-resolution, flow cytometry-based hematology analyzer
      (CellDyn 3000) and a centrifugal quantitative buffy coat hematology system (QBC
      I). We have analyzed the hemoglobin values of 163 individual blood samples. Bland
      Altman analysis showed that the methods agreed only poorly: mean differences were
      1.0 g/dL with limits of agreement (LOA) of -1.2 g/dL to 3.2 g/dL for the
      comparison of DHT and CellDyn measurements, 0.5 g/dL with LOA of -2.0 g/dL to 3.0
      g/dL for the comparison of DHT with QBC measurements, and 0.5 g/dL with LOA of 
      1.1 g/dL to 2.1 g/dL for the comparison of QBC with CellDyn measurements. We
      conclude that the poor agreement of the DHT with the CellDyn does not permit the
      use of the DHT for critical hemoglobin measurements, particularly in transfusion
      services.

PMID- 15569808
TI  - Recent advances in the monitoring and management of diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is still a major contributor to morbidity and
      mortality in diabetes. The triad of hyperglycaemia, ketosis and acidosis can be
      diagnosed within a few minutes of the patient presenting, by measuring blood
      glucose and ketones using a meter, and venous blood pH on a blood gas analyser.
      Quantifying ketosis allows accurate distinction between simple hyperglycaemia and
      metabolic decompensation. We review the management of DKA, and the emerging role
      of near-patient testing in diagnosing ketosis and monitoring its resolution.

PMID- 15569809
TI  - New world mucosal and cutaneous leishmaniasis: an emerging health problem among
      British travellers.
AB  - BACKGROUND: Mucosal leishmaniasis (ML) is an important complication of new world
      cutaneous leishmaniasis (CL) caused by species of the Leishmania Viannia
      subgenus. Previous reports of ML among travellers to Latin America are few. AIMS:
      To determine the annual number of cases of CL due to L. Viannia species diagnosed
      at this institution and to correlate this with changing patterns of travel.
      Secondly, to document the clinical presentation, diagnosis, treatment and outcome
      of ML at this institution. DESIGN: Retrospective observational study. METHODS:
      Data were collected from a clinical database, laboratory records, patient case
      notes and an international passenger survey. RESULTS: Between 1995 and 2003, the
      annual number of cases of CL (total 79) steadily increased from 4 per year to 18
      per year; the estimated number of travellers from the UK to Latin America
      increased 3.5-fold. Six cases of ML were diagnosed among British travellers in
      1995 (1), 1997 (1) and 2002 (4). These infections were acquired in Bolivia (3),
      Colombia (2) and Belize (1). Nasopharyngeal symptoms developed 0-15 months after
      returning to the UK. Four patients had concurrent CL at diagnosis. Diagnosis of
      ML was delayed up to 6 months from the onset of symptoms. Mucosal biopsies from
      all 6 patients were PCR-positive for L. (Viannia) DNA; microscopy and culture
      were less sensitive. ML relapsed in one patient following treatment. DISCUSSION:
      Increasing travel to Latin America from the UK was associated with an increasing
      number of diagnoses of L. Viannia CL. ML is likely to emerge as a more frequently
      imported infection among such travellers. Familiarity with these diseases is
      important for prompt diagnosis and optimal management.

PMID- 15569810
TI  - Chronic Strongyloides stercoralis infection in former British Far East prisoners
      of war.
AB  - BACKGROUND: Chronic infections with the nematode worm Strongyloides stercoralis
      can occur in former WWII Far East prisoners of war (FEPOWs). The condition may be
      asymptomatic, but frequently causes a characteristic urticarial 'larva currens'
      rash. Under conditions of immunosuppression (particularly systemic corticosteroid
      treatment) potentially fatal dissemination of larvae ('hyperinfection') may
      occur. AIM: To review our total experience of strongyloidiasis in former FEPOWs,
      and investigate its prevalence, characteristics and risk factors. DESIGN:
      Retrospective case series. METHODS: We reviewed 2072 records of all FEPOWs seen
      at the Liverpool School of Tropical Medicine, 1968-2002. Cases with
      strongyloidiasis were compared with non-infected controls. RESULTS: There were
      248 (12%) with strongyloidiasis. Diagnostic features included larva currens rash
      (70%), eosinophilia (66%), positive faecal culture (30%), positive faecal
      microscopy (26%), and positive serology (64%). Mean (+/-SD) age of cases was 65
      +/- 7 years, and as expected, their blood eosinophil counts were significantly
      higher than controls (775 vs. 238 x 10(6)/l, p < 0.001). Captivity on the Thai
      Burma Railway (vs. elsewhere) was significantly associated with strongyloidiasis
      (78% cases vs. 40% controls, OR 4.19, CI 2.70-6.81, p < 0.001). In terms of
      prevalence, strongyloidiasis occurred in 166/1032 men imprisoned on the Burma
      Railway (16.1%). Malaria (88% vs. 69%, p < 0.001) and tropical ulcer (53% vs.
      42%, p < 0.02) were more common amongst cases than controls, probably because
      these diseases were very common on the Burma Railway. DISCUSSION: S. stercoralis
      infection is common amongst ex-FEPOWs, particularly those from the Thai-Burma
      Railway project. It is usually characterized by a 'larva currens' rash and marked
      eosinophilia. The condition is eminently treatable, and continued diagnostic
      surveillance is needed, if cases of potentially fatal hyperinfection are to be
      avoided.

PMID- 15569811
TI  - Preventing venous thromboembolism in acute medical patients.
AB  - BACKGROUND: While extensive data support the clinical benefit and cost
      effectiveness of routine thromboprophylaxis in surgical patients, the use of this
      approach in medical patients has been controversial. However, recent data, mainly
      from the MEDENOX trial, support routine thromboprophylaxis in acutely ill medical
      patients. AIM: To determine attitudes towards VTE prevention in such patients, in
      departments of internal medicine in Israel. DESIGN: Questionnaire-based survey.
      METHODS: A questionnaire regarding aspects of VTE prophylaxis was mailed to all
      heads of internal medicine departments in Israel (n = 90). The questionnaire also
      included data concerning VTE prevention measures in specific acute medical
      illnesses, based on the MEDENOX study population. RESULTS: Fifty-eight (64%)
      departments returned the questionnaire. Forty-seven (81%) of them considered VTE
      a clinical problem in their departments, but only 37 (63%) had a routine VTE
      prevention policy. The most frequently used modality for VTE prophylaxis was low
      molecular-weight heparin. There was little agreement concerning the exact
      indications or risk factors in which VTE prophylaxis measures should be used,
      except the combination of acute medical disabling illness and previous VTE.
      DISCUSSION: The results emphasize the need for detailed guidelines and risk
      assessment models for VTE prevention treatments in acutely ill medical patients,
      as well as better education for physicians.

PMID- 15569812
TI  - End-of-life preferences in elderly patients admitted for heart failure.
AB  - BACKGROUND: Heart failure is increasing in prevalence and incidence, with
      considerable mortality among the elderly. AIM: To determine preferences
      concerning cardiopulmonary-resuscitation (CPR) and end-of-life care in elderly
      patients hospitalized for heart failure. DESIGN: Prospective interview-based
      survey. METHODS: Patients >64 years old admitted for acute heart failure were
      interviewed to address their preferences regarding end-of-life care and cardio
      pulmonary resuscitation (CPR) when facing the last stages of their disease.
      RESULTS: We interviewed 80 patients (mean age 79 years; 58% women). Thirty-two
      (40%) expressed a wish not to have CPR. Only two had previously discussed their
      CPR preferences with their physicians. When recovery from the illness was
      considered unlikely, 40 (50%) participants preferred to receive treatment at
      home, 32 (40%) preferred in-hospital management, and 8 (10%) were unsure. Thirty
      three patients (41%) expressed a desire for spiritual support, 38 (48%) said not
      and the remaining 9 (11%) were indifferent. DISCUSSION: Advance planning of end
      of-life procedures and doctor-patient communication regarding these items remains
      poor and must be improved.

PMID- 15569813
TI  - Plasma lipid peroxides: relationships to cardiovascular risk factors and
      prevalent cardiovascular disease.
AB  - BACKGROUND: The epidemiology of plasma lipid peroxides, which may play a role in
      atherogenesis, has not been well defined. AIM: To study the relationships of
      plasma lipid peroxides to cardiovascular risk factors in a random population
      sample. DESIGN: Random, age- and sex-stratified population sample. METHODS: We
      studied 739 men and women aged 25-74 years. Lipid peroxides were assayed by the
      thiobarbituric acid (TBA) assay for malondialdehyde (MDA) in stored plasma
      samples. RESULTS: Lipid peroxide levels increased with age. In men, lipid
      peroxides were significantly associated with smoking habit. Lipid peroxides
      correlated with non-fasting serum triglycerides (r = 0.33; p < 0.0001) in both
      sexes. Weaker associations were observed for cholesterol, high-density
      lipoprotein cholesterol (inversely), body mass index, fibrinogen and white cell
      count; as well as an inverse association with serum vitamin C in men. DISCUSSION:
      These findings clarify the relationships of plasma lipid peroxides to
      cardiovascular risk factors; and are consistent with the hypothesis that lipid
      peroxidation may be one mechanism through which several risk factors may promote
      cardiovascular disease.

PMID- 15569814
TI  - The obesity epidemic: prospects for prevention.
AB  - Some 20-25% of UK adults are obese according to the WHO criterion (BMI >/=30
      kg/m(2)). Type 2 diabetes, increasingly recognized as a major complication of
      overweight and obesity, is beginning to appear in UK adolescents, following the
      trends in the US. Epidemiological data indicate that the prevalence of overweight
      and obesity has doubled or tripled in the past few decades in the US, in Europe,
      and even in many developing countries. Thus obesity is increasingly seen as a
      public health problem requiring concerted action by both governmental and non
      governmental organizations. A sound understanding of the root causes is crucial,
      if strategies for the prevention and treatment of this epidemic are to be
      developed. Many epidemiological studies suggest that physical activity at work,
      school or at leisure has declined to minimal levels, and that sedentary
      behaviours such as television viewing and computer games have become major
      pastimes. Thus energy requirements are substantially less than those for recent
      generations. Further, the food industry produces high-calorie foods which
      children and adults consume as snack meals, giving a substantial surfeit to their
      daily energy requirement. In children, a few school-based, preventive
      intervention trials have shown some promising results. Many negative trials have
      also been reported, and practical difficulties remain in the widespread
      implementation of appropriate protocols. Initiatives have been introduced by the
      government to increase the physical education syllabus in school to a minimum of
      2 h/week, and the promotion of fruit and vegetables. Further research is required
      on the physiological and psychological causes of overweight and obesity in
      children and adults, and randomized, controlled, school and community-based
      trials are required to pilot preventative initiatives. Monitoring of the progress
      in prevention at both organizational and outcome level is required, and also of
      adverse outcomes such as a rise in the prevalence of eating disorders.

PMID- 15569815
TI  - Isolated left ventricular non-compaction, not hypertrophic cardiomyopathy.

PMID- 15569818
TI  - Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons
      from DGAT1-deficient mice.
AB  - Because the ability to make triglycerides is essential for the accumulation of
      adipose tissue, inhibition of triglyceride synthesis may ameliorate obesity and
      its related medical consequences. Acyl coenzyme A (CoA):diacylglycerol
      acyltransferase 1 (DGAT1) is 1 of 2 DGAT enzymes that catalyze the final reaction
      in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 are
      resistant to obesity and have increased sensitivity to insulin and leptin. DGAT1
      deficient mice are also resistant to diet-induced hepatic steatosis. The effects
      of DGAT1 deficiency on energy and glucose metabolism result in part from the
      altered secretion of adipocyte-derived factors. Although complete DGAT1
      deficiency causes alopecia and impairs development of the mammary gland, these
      abnormalities are not observed in mice with partial DGAT1 deficiency. These
      findings suggest that pharmacological inhibition of DGAT1 may be a feasible
      therapeutic strategy for human obesity and type 2 diabetes.

PMID- 15569819
TI  - Cytochrome P4502C9-derived epoxyeicosatrienoic acids induce the expression of
      cyclooxygenase-2 in endothelial cells.
AB  - OBJECTIVE: Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to
      epoxyeicosatrienoic acids (EETs). CYP2C9-derived EETs elicit endothelial cell
      proliferation and angiogenesis, but the signaling pathways involved are
      incompletely understood. Because cyclooxygenase-2 (COX-2) is involved in
      angiogenesis, we determined whether a link exists between CYP2C9 and COX-2
      expression. METHODS AND RESULTS: Human umbilical vein endothelial cells were
      infected with CYP2C9 sense or antisense adenoviral constructs. Overexpression of
      CYP2C9 increased COX-2 promoter activity, an effect accompanied by a significant
      increase in COX-2 protein expression and elevated prostacyclin production. The
      CYP2C9-induced expression of COX-2 was inhibited by the CYP2C9 inhibitor,
      sulfaphenazole, whereas 11,12-EET increased COX-2 expression. Overexpression of
      CYP2C9 and stimulation with 11,12-EET increased intracellular cAMP levels and
      stimulated DNA-binding of the cAMP-response element-binding protein. The protein
      kinase A inhibitor, KT5720, attenuated the CYP2C9-induced increase in COX-2
      promoter activity and protein expression. Overexpression of CYP2C9 stimulated
      endothelial tube formation, an effect that was attenuated by the COX-2 inhibitor
      celecoxib. Identical responses were observed in cells preconditioned by cyclic
      strain to increase CYP2C expression. CONCLUSIONS: These data indicate that CYP2C9
      derived EETs induce the expression of COX-2 in endothelial cells via a cAMP
      dependent pathway and that this mechanism contributes to CYP2C9-induced
      angiogenesis. Overexpression of cytochrome P450 (CYP) 2C9 in endothelial cells
      increased cAMP levels, stimulated the cAMP-response element-binding protein, and
      enhanced cyclooxygenase-2 (COX-2) promoter activity, protein expression, and
      prostacyclin production. CYP2C9 overexpression stimulated endothelial tube
      formation, which was attenuated by the COX-2 inhibitor celecoxib. Thus, COX-2
      contributes to CYP2C9-induced angiogenesis.

PMID- 15569820
TI  - Effects of exercise training and deconditioning on platelet aggregation induced
      by alternating shear stress in men.
AB  - OBJECTIVE: Alternating shear stress, which resembles the flow condition in
      stenotic arteries, induces platelet aggregation. This study investigated how
      exercise training and deconditioning influence alternating shear-induced platelet
      aggregation (ASIPA) and clarify the mechanisms underlying ASIPA. METHODS AND
      RESULTS: Thirty healthy male sedentary subjects were randomly divided into
      control and trained groups. The trained men were trained on a bicycle ergometer
      at approximately 60% of maximal oxygen consumption for 30 minutes per day, 5 days
      per week for 8 weeks, and then were deconditioned for 8 weeks. The experimental
      results indicate the following: (1) short-term strenuous exercise increases the
      extent of ASIPA and is accompanied by increased the von Willebrand factor (vWF)
      binding and P-selectin expression on platelets in both the control and trained
      groups, whereas the enhancement of platelet function decreases after exercise
      training in trained subjects; (2) at rest and immediately after exercise, ASIPA
      and the vWF binding and P-selectin expression on platelets are reduced by
      training, but remain unchanged in the control group; and (3) deconditioning
      reverses the effects of training on resting and postexercise state. CONCLUSIONS:
      Exercise training suppresses the extent of ASIPA, probably by reducing vWF
      binding to platelets and P-selectin expression on platelets. However,
      deconditioning reverses the training effects. This investigation shows that
      exercise training decreases resting and severe exercise-promoted platelet
      aggregation induced by alternating shear stress (ASIPA); moreover, this effect is
      accompanied by reduced the von Willebrand factor binding and P-selectin
      expression on platelets. However, the effects of training on ASIPA are reversed
      to the pretraining state after deconditioning.

PMID- 15569821
TI  - Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor
      cells in patients with coronary artery disease.
AB  - OBJECTIVE: Endothelial progenitor cells (EPCs) that may repair vascular injury
      are reduced in patients with coronary artery disease (CAD). We reasoned that EPC
      number and function may be increased by granulocyte colony-stimulating factor (G
      CSF) used to mobilize hematopoietic progenitor cells in healthy donors. METHODS
      AND RESULTS: Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063%
      versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+)
      cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006%
      MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters
      of cells in culture, with out-growth consistent with mature endothelial phenotype
      (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05)
      or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for
      5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/
      10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/
      0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed
      the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming
      clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a
      decline to 9+/-4/well at 2 weeks (P=0.06). CONCLUSIONS: Despite reduced EPCs
      compared with healthy controls, patients with CAD respond to G-CSF with increases
      in EPC number and homing receptor expression in the circulation and endothelial
      out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in
      coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered
      to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype;
      (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing
      of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture.
      Whether EPCs mobilized into the circulation will be useful for the purpose of
      initiating vascular growth and myocyte repair in coronary artery disease patients
      must be tested in clinical trials.

PMID- 15569822
TI  - Statins and blood coagulation.
AB  - The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors
      (statins) have been shown to exhibit several vascular protective effects,
      including antithrombotic properties, that are not related to changes in lipid
      profile. There is growing evidence that treatment with statins can lead to a
      significant downregulation of the blood coagulation cascade, most probably as a
      result of decreased tissue factor expression, which leads to reduced thrombin
      generation. Accordingly, statin use has been associated with impairment of
      several coagulant reactions catalyzed by this enzyme. Moreover, evidence
      indicates that statins, via increased thrombomodulin expression on endothelial
      cells, may enhance the activity of the protein C anticoagulant pathway. Most of
      the antithrombotic effects of statins are attributed to the inhibition of
      isoprenylation of signaling proteins. These novel properties of statins,
      suggesting that these drugs might act as mild anticoagulants, may explain, at
      least in part, the therapeutic benefits observed in a wide spectrum of patients
      with varying cholesterol levels, including subjects with acute coronary events.
      The HMG-CoA reductase inhibitors (statins) have been shown to exhibit several
      vascular protective effects, including antithrombotic properties, that are not
      related to changes in lipid profile. Treatment with statins can lead to a
      significant downregulation of the blood coagulation cascade, most probably as a
      result of decreased tissue factor expression, which leads to reduced thrombin
      generation.

PMID- 15569823
TI  - Tissue factor-factor VIIa signaling.
AB  - How does tissue factor (TF), whose principle role is to support clotting factor
      VIIa (FVIIa) in triggering the coagulation cascade, affect various
      pathophysiological processes? One of the answers is that TF interaction with
      FVIIa not only initiates clotting but also induces cell signaling via activation
      of G-protein-coupled protease activated receptors (PARs). Recent studies using
      various cell model systems and limited in vivo systems are beginning to define
      how TF-VIIa-induced signaling regulates cellular behavior. Signaling pathways
      initiated by both TF-VIIa protease activation of PARs and phosphorylation of the
      TF-cytoplasmic domain appear to regulate cellular functions. In the present
      article, we review the emerging data on the mechanism of TF-mediated cell
      signaling and how it regulates various cellular responses, with particular focus
      on TF-VIIa protease-dependent signaling.

PMID- 15569824
TI  - Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal
      hyperplasia.
AB  - OBJECTIVE: Phosphoinositide (PI) 3-kinase promotes vascular smooth muscle cell
      (VSMC) responses necessary for neointimal hyperplasia. We recently demonstrated
      that the inositol 3-phosphatase PTEN is expressed in VSMCs and that its
      overexpression inhibits these cellular responses. The purpose of this study was
      to determine the effects of adenovirus-mediated overexpression of PTEN on
      neointimal hyperplasia in vivo in the rat carotid injury model. METHODS AND
      RESULTS: Rat carotid arteries were balloon-injured and treated with a recombinant
      control adenovirus (AdEV) (n=6), an adenovirus encoding wild-type PTEN (AdPTEN)
      (n=8), or phosphate-buffered saline (sham) (n=5). Injured vessels demonstrated
      PTEN overexpression by Western blotting and immunohistochemistry after AdPTEN
      treatment. Neointimal hyperplasia was assessed 2 weeks after balloon injury and
      adenovirus administration. Compared with controls, AdPTEN treatment significantly
      decreased neointimal area and percent stenosis. To investigate the mechanisms of
      action of AdPTEN, vessels were harvested 3 days after balloon injury and virus
      infection. AdPTEN significantly increased medial cell apoptosis while decreasing
      proliferation of the remaining viable cells. CONCLUSIONS: PTEN overexpression
      potently inhibits neointimal hyperplasia through induction of apoptosis and
      inhibition of medial cell proliferation. These findings suggest that modulation
      of PTEN expression or activity may be a viable approach to treat neointimal
      hyperplasia. Phosphoinositide (PI) 3-kinase is a critical regulator of neointimal
      hyperplasia. The inositol 3-phosphatase PTEN modulates PI 3-kinase signaling by
      hydrolyzing the phospholipid products of PI 3-kinase, and overexpression of PTEN
      in vascular smooth muscle cells inhibits the cellular processes necessary for
      neointimal hyperplasia. The effects of adenovirus-mediated PTEN (AdPTEN)
      overexpression on neointimal hyperplasia were tested in the rat carotid injury
      model. Compared with control arteries, AdPTEN treatment significantly reduced
      neointimal area and percent stenosis by enhancing medial cell apoptosis and
      inhibiting proliferation of the remaining viable cells. Thus, PTEN provides a new
      target for the treatment of neointimal hyperplasia.

PMID- 15569825
TI  - In vitro angiogenic effects of pancreatic bile salt-dependent lipase.
AB  - OBJECTIVE: Bile salt-dependent lipase (BSDL), a lipolytic enzyme secreted in the
      duodenum by pancreatic acinar cells, has been detected in the serum of all
      patients and in atheromatous plaque, suggesting its potential implication in
      vascular pathophysiology. METHODS AND RESULTS: In vitro pancreatic BSDL evokes
      human umbilical vein endothelial cell (HUVEC) proliferation and chemotactic
      migration. BSDL at mitogen concentration is capable to heal wounded HUVEC
      monolayer and to promote capillary network formation. HUVEC proliferation depends
      on the displacement of basic fibroblast growth factor and vascular endothelial
      growth factor from the extracellular matrix and the activation of extracellular
      signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase, and
      focal adhesion kinase signaling pathways. CONCLUSIONS: For the first time to our
      knowledge, it is suggested that circulating BSDL could be involved in
      pathophysiological angiogenesis. We delineate the in vitro effects of pancreatic
      BSDL on endothelial cells, and we show that BSDL promotes proliferation,
      migration, capillary network formation, and wound-healing of HUVECs via the
      displacement of bFGF and VEGF from the ECM, suggesting that BSDL could be
      involved in angiogenesis.

PMID- 15569826
TI  - Atrial natriuretic peptide induces mitogen-activated protein kinase phosphatase-1
      in human endothelial cells via Rac1 and NAD(P)H oxidase/Nox2-activation.
AB  - The cardiovascular hormone atrial natriuretic peptide (ANP) exerts anti
      inflammatory effects on tumor necrosis factor-alpha-activated endothelial cells
      by inducing mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). The
      underlying mechanisms are as yet unknown. We aimed to elucidate the signaling
      pathways leading to an induction of MKP-1 by ANP in primary human endothelial
      cells. By using antioxidants, generation of reactive oxygen species (ROS) was
      shown to be crucially involved in MKP-1 upregulation. ANP was found to increase
      ROS formation in cultured cells as well as in the endothelium of intact rat lung
      vessels. We applied NAD(P)H oxidase (Nox) inhibitors (apocynin and gp91ds-tat)
      and revealed this enzyme complex to be crucial for superoxide generation and MKP
      1 expression. Moreover, by performing Nox2/4 antisense experiments, we identified
      Nox2 as the critically involved Nox homologue. Pull-down assays and confocal
      microscopy showed that ANP activates the small Rho-GTPase Rac1. Transfection of a
      dominant-negative (RacN17) and constitutively active Rac1 mutant (RacV12)
      indicated that ANP-induced superoxide generation and MKP-1 expression are
      mediated via Rac1 activation. ANP-evoked production of superoxide was found to
      activate c-Jun N-terminal kinase (JNK). Using specific inhibitors, we linked ANP
      induced JNK activation to MKP-1 expression and excluded an involvement of protein
      kinase C, extracellular signal-regulated kinase, and p38 MAPK. MKP-1 induction
      was shown to depend on activation of the transcription factor activator protein-1
      (AP-1) by using electrophoretic mobility shift assay and AP-1 decoys. In summary,
      our work provides insights into the mechanisms by which ANP induces MKP-1 and
      shows that ANP is a novel endogenous activator of endothelial Rac1 and Nox/Nox2.

PMID- 15569827
TI  - Role of nitric oxide in Ca2+ sensitivity of the slowly activating delayed
      rectifier K+ current in cardiac myocytes.
AB  - Sarcolemmal Ca2+ entry is a vital step for contraction of cardiomyocytes, but
      Ca2+ overload is harmful and may trigger arrhythmias and/or apoptosis. To
      maintain the amount of Ca2+ entry within an appropriate range, cardiomyocytes
      have feedback systems that tightly regulate ion channel activities in response to
      the changes in intracellular Ca2+ concentration ([Ca2+]i), thereby regulating
      Ca2+ entry. In guinea pig ventricular myocytes, Ca2+ ionophore, A23187, induced
      suppression of the L-type Ca2+ currents (I(Ca,L)) and enhancement of the slowly
      activating delayed rectifier K(+) currents (I(Ks)). At a low stimulation rate,
      I(Ca,L) suppression and I(Ks) enhancement contributed to the A23187-induced APD
      shortening with a similar magnitude, whereas at a high stimulation rate, I(Ks)
      enhancement dominantly contributed to APD shortening. I(Ks) enhancement induced
      by A23187 was attributable to actions of nitric oxide (NO), because they were
      inhibited by an inhibitor of NO synthase (NOS) and by a NO scavenger. A23187
      induced alterations of APD and I(Ks) were strongly suppressed by a NOS3
      inhibitor, but barely affected by a NOS1 inhibitor, suggesting that NOS3 was
      responsible for NO release in this phenomenon. Inhibition of calmodulin (CaM),
      but not Akt, blocked the enhancement of I(Ks) by A23187. Thus, CaM-dependent NOS3
      activation confers the selective Ca2+-sensitivity on I(Ks). Ca2+-induced I(Ks)
      enhancement and resultant APD shortening potentially act as a physiological
      regulatory mechanism of Ca2+ recycling, because they were observed at a
      physiological range of [Ca2+]i in cardiac myocytes and are induced by
      physiologically relevant Ca2+ loading, such as digitalis application and rise in
      extracellular Ca2+ concentration.

PMID- 15569828
TI  - Bone marrow cells differentiate in cardiac cell lineages after infarction
      independently of cell fusion.
AB  - Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to
      differentiate into myocytes and coronary vessels. The claim has also been made
      that BMCs acquire a cell phenotype different from the blood lineages only by
      fusing with resident cells. Technical problems exist in the induction of
      myocardial infarction and the successful injection of BMCs in the mouse heart.
      Similarly, the accurate analysis of the cell populations implicated in the
      regeneration of the dead tissue is complex and these factors together may account
      for the negative findings. In this study, we have implemented a simple protocol
      that can easily be reproduced and have reevaluated whether injection of BMCs
      restores the infarcted myocardium in mice and whether cell fusion is involved in
      tissue reconstitution. For this purpose, c-kit-positive BMCs were obtained from
      male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP
      and the Y-chromosome were used as markers of the progeny of the transplanted
      cells in the recipient heart. By this approach, we have demonstrated that BMCs,
      when properly administrated in the infarcted heart, efficiently differentiate
      into myocytes and coronary vessels with no detectable differentiation into
      hemopoietic lineages. However, BMCs have no apparent paracrine effect on the
      growth behavior of the surviving myocardium. Within the infarct, in 10 days,
      nearly 4.5 million biochemically and morphologically differentiated myocytes
      together with coronary arterioles and capillary structures were generated
      independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages
      and have an important therapeutic impact on ischemic heart failure.

PMID- 15569829
TI  - Characteristics of prolonged Ca2+ release events associated with the nuclei in
      adult cardiac myocytes.
AB  - Confocal microscopy was used to study the properties of nuclear Ca2+ regulation
      in adult ventricular myocytes. Prolonged nuclear Ca2+ release (PNCR) events were
      identified in both intact and permeabilized rat myocytes. PNCR occurred
      spontaneously and was restricted to localized regions at the ends of the
      elongated nuclei. Typically, PNCR took the form of a rapid rise in [Ca2+]
      followed by a maintained plateau. The mean duration of PNCR (1.78+/-0.19 seconds)
      was markedly greater than the half decay time for cytosolic Ca2+ sparks (31.2+/
      0.56 ms) obtained under the same conditions. The PNCR width at half maximum
      amplitude (5.0+/-0.2 microm) was also significantly greater than that of
      cytosolic Ca2+ sparks (2.6+/-0.05 microm) obtained under the same conditions.
      Experiments involving the use of syto-11 to accurately locate the nuclei
      demonstrated that PNCR originates from the nuclear envelope or a closely
      associated structure. The spatial spread of PNCR was asymmetrical, with greater
      diffusion of Ca2+ toward the center of the nucleus than the cytosol. Both PNCR
      and Ca2+ sparks were abolished by interventions that deplete SR Ca2+ stores or
      inhibit RYR activation. Experiments on intact, electrically stimulated cells
      revealed that diffusion of Ca2+ from the ends of the nucleus toward the center is
      a prominent feature of the nucleoplasmic Ca2+ transient. The possibility that
      recruitment of Ca2+ release sites involved in PNCR might influence the temporal
      and spatial characteristics of the nucleoplasmic [Ca2+] transient is considered.

PMID- 15569830
TI  - Impaired L-arginine transport and endothelial function in hypertensive and
      genetically predisposed normotensive subjects.
AB  - BACKGROUND: Impaired endothelium-dependent NO-mediated vasodilation is a key
      feature of essential hypertension and may precede the increase in blood pressure.
      We investigated whether transport of the NO precursor L-arginine is related to
      decreased endothelial function. METHODS AND RESULTS: Radiotracer kinetics ([3H]L
      arginine) were used to measure forearm and peripheral blood mononuclear cell
      arginine uptake in hypertensive subjects (n=12) and in 2 groups of healthy
      volunteers with (n=15) and without (n=15) a family history of hypertension. In
      conjunction, forearm blood flow responses to acetylcholine and sodium
      nitroprusside were measured before and after a supplemental intra-arterial
      infusion of L-arginine. In vivo and in vitro measures of L-arginine transport
      were substantially reduced in the essential hypertension and positive family
      history groups compared with the negative family history group; however, no
      difference was detected in peripheral blood mononuclear cell mRNA or protein
      expression levels for the cationic amino acid transporter CAT-1. Plasma
      concentrations of L-arginine and N(G),N(G')-dimethylarginine (ADMA) did not
      differ between groups. L-arginine supplementation improved the response to
      acetylcholine only in subjects with essential hypertension and positive family
      history. CONCLUSIONS: Similar to their hypertensive counterparts, normotensive
      individuals at high risk for the development of hypertension are characterized by
      impaired L-arginine transport, which may represent the link between a defective L
      arginine/NO pathway and the onset of essential hypertension. The observed
      transport defect is not due to apparent alterations in CAT-1 expression or
      elevated endogenous ADMA.

PMID- 15569831
TI  - Prenatal environmental tobacco smoke exposure promotes adult atherogenesis and
      mitochondrial damage in apolipoprotein E-/- mice fed a chow diet.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) exposure is recognized as a
      cardiovascular disease risk factor; however, the impact of prenatal ETS exposure
      on adult atherogenesis has not been examined. We hypothesized that in utero ETS
      exposure promotes adult atherosclerotic lesion formation and mitochondrial
      damage. METHODS AND RESULTS: Atherosclerotic lesion formation, mitochondrial DNA
      damage, antioxidant activity, and oxidant load were determined in cardiovascular
      tissues from adult apolipoprotein E-/- mice exposed to either filtered air or ETS
      in utero and fed a standard chow diet (4.5% fat) from weaning until euthanasia.
      All parameters were significantly altered in male mice exposed in utero to ETS.
      CONCLUSIONS: These data support the hypothesis that prenatal ETS exposure is
      sufficient to promote adult cardiovascular disease development.

PMID- 15569832
TI  - Overexpression of wild-type heat shock protein 27 and a nonphosphorylatable heat
      shock protein 27 mutant protects against ischemia/reperfusion injury in a
      transgenic mouse model.
AB  - BACKGROUND: The small heat shock protein 27 (hsp27) increases in expression with
      ischemia/reperfusion (I/R) insult in the heart. One feature of the small hsps is
      their ability to oligomerize and form intracellular aggregates. Oligomerization
      pattern is governed by the phosphorylation state of the protein that may
      influence their ability to protect against cellular stresses. METHODS AND
      RESULTS: We generated transgenic (tg) mice that overexpress a wild-type human
      hsp27 (hsp27tg) protein or a mutant hsp27 protein (mut-hsp27tg), in which serine
      residues (aa15, aa78, and aa82) were replaced by alanine residues, rendering them
      incapable of phosphorylation. Using a Langendorff perfusion model and an
      intraventricular balloon, we subjected hearts to 20 minutes of ischemia followed
      by 1 hour of reperfusion. During reperfusion, negative and positive pressure
      derivatives as well as developed pressures were significantly higher in both
      hsp27tg and mut-hsp27tg compared with control (P<0.01) mice, with no significant
      difference between hsp27tg and mut-hsp27tg. Creatine kinase release during
      reperfusion was higher in control compared with both hsp27tg and mut-hsp27tg
      (P<0.05). Malondialdehyde content as well as protein oxidation products were
      lower in mut-hsp27tg compared with control (P<0.05). hsp27tg hearts possessed
      oligomers that ranged in size from small to large, whereas mut-hsp27tg hearts
      contained no small oligomers. CONCLUSIONS: These results indicate that in a tg
      mouse model, overexpression of either wild-type hsp27 or a nonphosphorylatable
      hsp27 mutant was equally capable of protecting the heart from I/R injury.
      Furthermore, the phosphorylation status of hsp27 may influence its ability to
      decrease oxidative stress.

PMID- 15569833
TI  - Angiotensin II induces neutrophil accumulation in vivo through generation and
      release of CXC chemokines.
AB  - BACKGROUND: Angiotensin II (Ang II) is implicated in the development of cardiac
      ischemic disorders in which prominent neutrophil accumulation occurs. Ang II can
      be generated intravascularly by the renin-angiotensin system or extravascularly
      by mast cell chymase. In this study, we characterized the ability of Ang II to
      induce neutrophil accumulation. METHODS AND RESULTS: Intraperitoneal
      administration of Ang II (1 nmol/L) induced significant neutrophil recruitment
      within 4 hours (13.3+/-2.3x10(6) neutrophils per rat versus 0.7+/-0.5x10(6) in
      control animals), which disappeared by 24 hours. Maximal levels of CXC chemokines
      were detected 1 hour after Ang II injection (577+/-224 pmol/L cytokine-inducible
      neutrophil chemoattractant [CINC]/keratinocyte-derived chemokine [KC] versus 5+/
      3, and 281+/-120 pmol/L macrophage inflammatory protein [MIP-2] versus 14+/-6).
      Intravital microscopy within the rat mesenteric microcirculation showed that the
      short-term (30 to 60 minutes) leukocyte-endothelial cell interactions induced by
      Ang II were attenuated by an anti-rat CINC/KC antibody and nearly abolished by
      the CXCR2 antagonist SB-517785-M. In human umbilical vein endothelial cells
      (HUVECs) or human pulmonary artery media in culture, Ang II induced interleukin
      (IL)-8 mRNA expression at 1, 4, and 24 hours and the release of IL-8 at 4 hours
      through interaction with Ang II type 1 receptors. When HUVECs were pretreated
      with IL-1 for 24 hours to promote IL-8 storage in Weibel-Palade bodies, the Ang
      II-induced IL-8 release was more rapid and of greater magnitude. CONCLUSIONS: Ang
      II provokes rapid neutrophil recruitment, mediated through the release of CXC
      chemokines such as CINC/KC and MIP-2 in rats and IL-8 in humans, and may
      contribute to the infiltration of neutrophils observed in acute myocardial
      infarction.

PMID- 15569834
TI  - Factor VLeiden inhibits fibrinolysis in vivo.
AB  - BACKGROUND: Factor V(Leiden) (fV(Leiden)) predisposes to thrombosis by enhancing
      thrombin formation. This study tested the hypothesis that fV(Leiden) inhibits
      fibrinolysis in vivo. METHODS AND RESULTS: Radiolabeled clots were injected into
      the jugular veins of wild-type mice and mice heterozygous (fV(+/Q)) or homozygous
      (fV(Q/Q)) for fV(Leiden). Mean percent clot lysis 5 hours later was significantly
      reduced in fV(Q/Q) mice (14.3+/-3.6%, n=13) compared with wild-type mice (40.2+/
      7.0%, n=17; P<0.01) and intermediate in fV(+/Q) mice (29.4+/-8.7%, n=9; P<0.03
      versus fV(Q/Q), P=0.36 versus wild type). The rate of in vitro lysis of plasma
      clots prepared from fV(+/Q) or fV(Q/Q) mice was significantly slower than that of
      wild-type plasma clots, whereas in vitro clot lysis did not differ significantly
      between groups after inhibiting thrombin-activatable fibrinolysis inhibitor.
      CONCLUSIONS: fV(Leiden) inhibits fibrinolysis in vivo, suggesting an additional
      pathway by which this mutation promotes thrombosis.

PMID- 15569835
TI  - Additive beneficial effects of losartan combined with simvastatin in the
      treatment of hypercholesterolemic, hypertensive patients.
AB  - BACKGROUND: Biological mechanisms underlying statin and angiotensin II type 1
      receptor blocker therapies differ. Therefore, we compared vascular and metabolic
      responses to these therapies either alone or in combination in
      hypercholesterolemic, hypertensive patients. METHODS AND RESULTS: This was a
      randomized, double-blind, placebo-controlled crossover trial with 3 treatment
      arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven
      hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and
      placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo
      daily during each 2-month treatment period. Losartan alone or combined therapy
      significantly reduced blood pressure compared with simvastatin alone. Compared
      with losartan alone, simvastatin alone or combined therapy significantly changed
      lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator
      response to hyperemia and decreased plasma malondialdehyde and monocyte
      chemoattractant protein-1 levels relative to baseline measurements. However,
      these parameters were changed to a greater extent with combined therapy compared
      with simvastatin or losartan alone (both P<0.001 and P=0.030 for monocyte
      chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone
      significantly increased plasma adiponectin levels and insulin sensitivity
      (determined by QUICKI) relative to baseline measurements. These changes were
      significantly greater than in the group treated with simvastatin alone (P<0.001
      for adiponectin, P=0.029 for QUICKI by ANOVA). CONCLUSIONS: Simvastatin combined
      with losartan improves endothelial function and reduces inflammatory markers to a
      greater extent than monotherapy with either drug in hypercholesterolemic,
      hypertensive patients.

PMID- 15569836
TI  - Toll-like receptor 2 mediates Staphylococcus aureus-induced myocardial
      dysfunction and cytokine production in the heart.
AB  - BACKGROUND: Staphylococcus aureus sepsis is associated with significant
      myocardial dysfunction. Toll-like receptor 2 (TLR2) mediates the inflammatory
      response to S aureus and may trigger an innate immune response in the heart. We
      hypothesized that a TLR2 deficiency would attenuate S aureus-induced cardiac
      proinflammatory mediator production and the development of cardiac dysfunction.
      METHODS AND RESULTS: Wild-type and TLR2-deficient (TLR2D) mice were studied. S
      aureus challenge significantly increased tumor necrosis factor, interleukin
      1beta, and nitric oxide expression in hearts of wild-type mice. This response was
      significantly blunted in TLR2D mice. Hearts from TLR2D mice had impaired S aureus
      induced activation of interleukin-1 receptor-associated kinase, c-Jun NH2
      terminal kinase, nuclear factor-kappaB, and activator protein-1. Moreover, hearts
      from TLR2D mice were protected against S aureus-induced contractile dysfunction.
      CONCLUSIONS: These results show for the first time that TLR2 signaling
      contributes to the loss of myocardial contractility and cytokine production in
      the heart during S aureus sepsis.

PMID- 15569837
TI  - Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several
      chromosomal regions.
AB  - BACKGROUND: Genetic factors have an important role in the pathogenesis of
      intracranial aneurysm (IA). The results of previous studies have suggested
      several loci. METHODS AND RESULTS: From 29 IA families with > or =3 individuals
      affected by IA, we used nonparametric (model-free) methods for linkage analyses,
      using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3
      regions on chromosomes 17cen (maximum nonparametric logarithm of the odds score
      [MNS] = 3.00, nominal P=0.001), 19q13 (MNS=2.15, nominal P=0.020), and Xp22
      (MNS=2.16, nominal P=0.019). We tested 4 candidate genes in these regions: the
      microfibril-associated protein 4 gene (MFAP4) and the promoter polymorphism of
      the inducible nitric oxide synthase gene (NOS2A) on chromosome 17cen, the epsilon
      genotypes of the apolipoprotein E gene (APOE) on chromosome 19q13, and the
      angiotensin I converting enzyme 2 gene (ACE2) on chromosome Xp22. Associations of
      their polymorphisms with IA were evaluated by a case-control study (100 cases: 29
      probands from IA families and 71 unrelated subjects with IAs, 100 unrelated
      control subjects [unaffected members with IAs and absence of family history of
      IAs]). However, the case-control study showed that none of the polymorphisms of
      the examined genes had associations with IA. CONCLUSIONS: A genome-wide scan in
      29 Japanese families with a high degree of familial clustering revealed 1
      suggestive linkage region on chromosome 17cen and 2 potentially interesting
      regions on chromosomes 19q13 and Xp22. These regions were consistent with
      previous findings in various populations.

PMID- 15569838
TI  - Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK
      pathway: implications for atherosclerotic endothelial dysfunction.
AB  - BACKGROUND: Arginase competes with endothelial nitric oxide synthase (eNOS) for
      the substrate l-arginine and decreases NO production. This study investigated
      regulatory mechanisms of arginase activity in endothelial cells and its role in
      atherosclerosis. METHODS AND RESULTS: In human endothelial cells isolated from
      umbilical veins, thrombin concentration- and time-dependently stimulated arginase
      enzymatic activity, reaching a 1.9-fold increase (P<0.001) at 1 U/mL for 24
      hours. The effect of thrombin was prevented by C3 exoenzyme or the HMG-CoA
      reductase inhibitor fluvastatin, which inhibit RhoA, or by the ROCK inhibitors Y
      27632 and HA-1077. Adenoviral expression of constitutively active RhoA or ROCK
      mutants enhanced arginase activity (approximately 3-fold, P<0.001), and the
      effect of active RhoA mutant was inhibited by the ROCK inhibitors. Neither
      thrombin nor the active RhoA/ROCK mutants affected arginase II protein level, the
      only isozyme detectable in the cells. Moreover, a significantly higher arginase
      II activity (1.5-fold, not the protein level) and RhoA protein level (4-fold)
      were observed in atherosclerotic aortas of apoE-/- compared with wild-type mice.
      Interestingly, l-arginine (1 mmol/L), despite a significantly higher eNOS
      expression in aortas of apoE-/- mice, evoked a more pronounced contraction, which
      was reverted to a greater vasodilation by the arginase inhibitor l-norvaline (20
      mmol/L) compared with the wild-type animals (n=5, P<0.001). CONCLUSIONS: Thrombin
      enhances arginase activity via RhoA/ROCK in human endothelial cells. Higher
      arginase enzymatic activity is involved in atherosclerotic endothelial
      dysfunction in apoE-/- mice. Targeting vascular arginase may represent a novel
      therapeutic possibility for atherosclerosis.

PMID- 15569839
TI  - Computed tomographic analysis of the anatomy of the left atrium and the
      esophagus: implications for left atrial catheter ablation.
AB  - BACKGROUND: During left atrial (LA) catheter ablation, an atrioesophageal fistula
      can develop as a result of thermal injury of the esophagus during ablation along
      the posterior LA. No in vivo studies have examined the relationship of the
      esophagus to the LA. The purpose of this study was to describe the topographic
      anatomy of the esophagus and the posterior LA by use of CT. METHODS AND RESULTS:
      A helical CT scan of the chest with 3D reconstruction was performed in 50
      patients (mean age, 54+/-11 years) with atrial fibrillation before an ablation
      procedure. Consecutive axial and sagittal sections of the CT scan were examined
      to determine the relationship, size, and thickness of the tissue layers between
      the LA and the esophagus. The mean length and width of the esophagus in contact
      with the posterior LA were 58+/-14 and 13+/-6 mm, respectively. The esophagus had
      a variable course along the posterior LA. The esophagus was close (10+/-6 mm from
      the ostia) and parallel to the left-sided pulmonary veins (PVs) in 56% of
      patients and had an oblique course from the left superior PV to the right
      inferior PV in 36% of patients. The mean thicknesses of the posterior LA and
      anterior esophageal walls were 2.2+/-0.9 and 3.6+/-1.7 mm, respectively. In 98%
      of patients, there was a fat layer between the esophagus and the posterior LA.
      However, this layer was often discontinuous. CONCLUSIONS: The esophagus and
      posterior LA wall are in close contact over a large area that may often lie
      within the atrial fibrillation ablation zone, and there is marked variation in
      the anatomic relationship of the esophagus and the posterior LA. Both the
      esophageal and atrial walls are quite thin. However, a layer of adipose tissue
      may serve to insulate the esophagus from thermal injury, explaining why
      atrioesophageal fistulas are rare.

PMID- 15569840
TI  - Chronic kidney disease, cardiovascular risk, and response to angiotensin
      converting enzyme inhibition after myocardial infarction: the Survival And
      Ventricular Enlargement (SAVE) study.
AB  - BACKGROUND: Persons with end-stage renal disease and those with lesser degrees of
      chronic kidney disease (CKD) have an increased risk of death after myocardial
      infarction (MI) that is not fully explained by associated comorbidities. Future
      cardiovascular event rates and the relative response to therapy in persons with
      mild to moderate CKD are not well characterized. METHODS AND RESULTS: We
      calculated the estimated glomerular filtration rate (eGFR) using the 4-variable
      Modification of Diet in Renal Disease method in 2183 Survival And Ventricular
      Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days
      after MI) with left ventricular ejection fraction < or =40% and serum creatinine
      <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to
      evaluate the relative hazard rates for death and cardiovascular events associated
      with reduced eGFR. Subjects with reduced eGFR were older and had more extensive
      comorbidities. The multivariable adjusted risk ratio for total mortality
      associated with reduced eGFR from 60 to 74, 45 to 59, and <45 mL x min(-1) x 1.73
      m(-2) (compared with eGFR > or =75 mL x min(-1) x 1.73 m(-2)) was 1.11 (0.86 to
      1.42), 1.24 (0.96 to 1.60) and 1.81 (1.32 to 2.48), respectively (P for trend
      =0.001). Similar adjusted trends were present for CV mortality (P=0.001),
      recurrent MI (P=0.017), and the combined CV mortality and morbidity outcome
      (P=0.002). The absolute benefit of captopril tended to be greater in subjects
      with CKD: 12.4 versus 5.5 CV events prevented per 100 subjects with (n=719) and
      without (n=1464) CKD, respectively. CONCLUSIONS: CKD was associated with a
      heightened risk for all major CV events after MI, particularly among subjects
      with an estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2).
      Randomization to captopril resulted in a reduction of CV events irrespective of
      baseline kidney function.

PMID- 15569841
TI  - Effects of ghrelin administration on left ventricular function, exercise
      capacity, and muscle wasting in patients with chronic heart failure.
AB  - BACKGROUND: Ghrelin is a novel growth hormone-releasing peptide that also induces
      vasodilation, inhibits sympathetic nerve activity, and stimulates feeding through
      growth hormone-independent mechanisms. We investigated the effects of ghrelin on
      left ventricular (LV) function, exercise capacity, and muscle wasting in patients
      with chronic heart failure (CHF). METHODS AND RESULTS: Human synthetic ghrelin (2
      microg/kg twice a day) was intravenously administered to 10 patients with CHF for
      3 weeks. Echocardiography, cardiopulmonary exercise testing, dual x-ray
      absorptiometry, and blood sampling were performed before and after ghrelin
      therapy. A single administration of ghrelin elicited a marked increase in serum
      GH (25-fold). Three-week administration of ghrelin resulted in a significant
      decrease in plasma norepinephrine (1132+/-188 to 655+/-134 pg/mL; P<0.001).
      Ghrelin increased LV ejection fraction (27+/-2% to 31+/-2%; P<0.05) in
      association with an increase in LV mass and a decrease in LV end-systolic volume.
      Treatment with ghrelin increased peak workload and peak oxygen consumption during
      exercise. Ghrelin improved muscle wasting, as indicated by increases in muscle
      strength and lean body mass. These parameters remained unchanged in 8 patients
      with CHF who did not receive ghrelin therapy. CONCLUSIONS: These preliminary
      results suggest that repeated administration of ghrelin improves LV function,
      exercise capacity, and muscle wasting in patients with CHF.

PMID- 15569842
TI  - Brachial artery vasodilator function and systemic inflammation in the Framingham
      Offspring Study.
AB  - BACKGROUND: In experimental studies, traditional risk factors and proinflammatory
      processes alter the regulatory functions of the vascular endothelium to promote
      atherosclerosis. These alterations include expression of leukocyte adhesion
      molecules and decreased bioavailability of endothelium-derived nitric oxide, an
      important regulator of vascular homeostasis and tone. The precise relations among
      risk factors, inflammation, and nitric oxide bioavailability remain uncertain.
      METHODS AND RESULTS: To test the hypothesis that inflammation impairs endothelial
      function in humans, we measured brachial artery flow-mediated dilation, reactive
      hyperemia, and serum concentrations of C-reactive protein (CRP), interleukin-6
      (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), and monocyte
      chemotactic protein-1 (MCP-1) in 2701 participants from the Framingham Study
      (mean age 61 years, 53% women). There were modest unadjusted inverse correlations
      between flow-mediated dilation and CRP, IL-6, and sICAM-1 (P<0.001 for all) that
      were rendered nonsignificant after accounting for traditional coronary risk
      factors. For reactive hyperemia, we observed inverse correlations with markers of
      inflammation in unadjusted models that were attenuated 57% to 74% after
      accounting for risk factors. However, partial correlations of CRP, IL-6, and
      sICAM-1 with reactive hyperemia remained significant. CONCLUSIONS: Our
      observations are consistent with the hypothesis that risk factors induce a state
      of inflammation that impairs vascular function. For flow-mediated dilation, we
      found no evidence that inflammation has additional effects beyond those
      attributable to traditional risk factors. The incremental contribution of CRP, IL
      6, and sICAM-1 to reactive hyperemia above and beyond known risk factors suggests
      that systemic inflammation may contribute to impaired vasomotor function in
      forearm microvessels.

PMID- 15569843
TI  - Amplified transmural dispersion of repolarization as the basis for
      arrhythmogenesis in a canine ventricular-wedge model of short-QT syndrome.
AB  - BACKGROUND: The short-QT syndrome is a new clinical entity characterized by
      corrected QT intervals <300 ms and a high incidence of ventricular tachycardia
      (VT) and fibrillation (VF). Gain-of-function mutations in the gene for outward
      potassium currents have been shown to underlie the congenital syndrome. The
      present study examined the cellular basis of VT/VF in an experimental model
      associated with short QT intervals created with a potassium channel activator.
      METHODS AND RESULTS: Transmembrane action potentials from epicardial and M
      regions, 4 transmural unipolar electrograms, and a pseudo-ECG were simultaneously
      recorded in canine arterially perfused left ventricular wedge preparations. At a
      basic cycle length of 2000 ms, pinacidil (2 to 3 mumol/L) abbreviated the QT
      interval from 303.7+/-5.4 to 247.3+/-6.9 ms (mean+/-SEM, P<0.0001). The maximal
      transmural dispersion of repolarization (TDR(max)) increased from 27.0+/-3.8 to
      64.9+/-9.2 ms (P<0.01), and an S2 applied to the endocardium induced a
      polymorphic VT (pVT) in 9 of 12 wedge preparations (P<0.01). Addition of
      isoproterenol (100 nmol/L, n=5) led to greater abbreviation of the QT interval, a
      further increase in TDR(max) (from 55.4+/-13.7 to 69.7+/-8.3 ms), and more
      enduring pVT. TDR(max) was correlated significantly with the T(peak)-T(end)
      interval under all conditions. The effects of pinacidil were completely reversed
      by glybenclamide (10 micromol/L, n=4) and partially reversed by E4031 (5
      micromol/L, n=5), which prevented induction of pVT in 3 of 5 preparations.
      CONCLUSIONS: Our data suggest that heterogeneous abbreviation of the action
      potential duration among different cell types spanning the ventricular wall
      creates the substrate for the genesis of VT under conditions associated with
      short QT intervals.

PMID- 15569844
TI  - Postprandial hypertriglyceridemia increases circulating levels of endothelial
      cell microparticles.
AB  - BACKGROUND: This study evaluated a possible relationship between levels of
      endothelial microparticles (EMPs), known to be a sensitive indicator of
      endothelial disturbance, and changes in postprandial lipid levels in healthy
      volunteers after a low- or high-fat meal. METHODS AND RESULTS: Eighteen healthy
      subjects without known cardiovascular risk factors were evaluated. Lipid and EMP
      levels were measured before and 1 and 3 hours after a single low- or high-fat
      isocaloric meal. The low-fat meal had no significant postprandial effect on EMPs
      or lipids compared with fasting levels. In contrast, a single high-fat meal
      significantly increased EMP levels after 1 and 3 hours, from 389+/-54 (thousands
      per milliliter) when fasting to 541+/-139 (P=0.0002) and 677+/-159 (P<0.0001),
      respectively, and correlated with a postprandial elevation in serum
      triglycerides. CONCLUSIONS: A single high-fat meal led to a significant elevation
      of plasma EMP levels in healthy, normolipidemic subjects and correlated with a
      postprandial elevation of serum triglycerides. EMPs may be an indirect marker of
      endothelial dysfunction or injury induced by postprandial triglyceride-rich
      lipoproteins.

PMID- 15569845
TI  - Images in cardiovascular medicine. Giant unruptured noncoronary sinus of Valsalva
      aneurysm.

PMID- 15569846
TI  - Images in cardiovascular medicine. Percutaneous replacement of the pulmonary
      valve in a 12-year-old child.

PMID- 15569847
TI  - Sphingolipids and atherosclerosis: a mechanistic connection? A therapeutic
      opportunity?

PMID- 15569848
TI  - Fixing the heart: must the brain pay the price?

PMID- 15569851
TI  - Prediction of heart failure by amino terminal-pro-B-type natriuretic peptide and
      C-reactive protein in subjects with cerebrovascular disease.
AB  - B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in
      persons at risk for congestive heart failure (CHF). However, limited data are
      available directly comparing BNP-related peptides and CRP in persons at risk of
      CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and
      together, for assessment of risk of CHF, we performed a nested case-control study
      of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke
      Study (PROGRESS), a placebo-controlled study of a perindopril-based blood
      pressure-lowering regimen among individuals with previous stroke or transient
      ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death,
      hospitalization, or withdrawal of randomized therapy during a mean follow-up of
      3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted
      CHF; the odds ratio for subjects in the highest compared with the lowest quarter
      was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence
      interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after
      adjustment for all other predictors. Screening for both markers provided better
      prognostic information than screening for either alone. Elevation of NT-proBNP
      above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and
      specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving
      perindopril-based therapy. We conclude that NT-proBNP and CRP are independent
      predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be
      markers of mechanisms of CHF pathogenesis distinct from those responsive to
      angiotensin-converting enzyme inhibitor-based therapy.

PMID- 15569852
TI  - Relations of serum uric acid to longitudinal blood pressure tracking and
      hypertension incidence.
AB  - Serum uric acid (UA) has been implicated in the pathogenesis of hypertension. We
      investigated the relationship of serum UA to hypertension incidence and blood
      pressure (BP) progression in 3329 Framingham Study participants (mean age 48.7
      years; 55.6% women) free of hypertension, myocardial infarction, heart failure,
      renal failure, or gout. At follow-up 4 years from baseline, 458 persons (13.8%)
      had developed hypertension, and 1201 persons (36.1%) had experienced progression
      to a higher BP stage. Age- and sex-adjusted rates of hypertension incidence
      increased progressively from 9.8% for the lowest quartile to 15.6% for the top
      quartile of serum UA; BP progression rates increased from 32.8% (lowest quartile)
      to 39.6% (top quartile). In multivariable analyses adjusting for age, sex, body
      mass index, diabetes, smoking, alcohol intake, serum creatinine, proteinuria,
      glomerular filtration rate, baseline BP, and interim weight change, a 1 SD higher
      serum UA was associated with an odds ratio (OR) of 1.17 (95% confidence interval
      [CI], 1.02 to 1.33) for developing hypertension, and an OR of 1.11 (95% CI, 1.01
      to 1.23) for BP progression. In analyses of a subsample of 3157 individuals not
      on antihypertensive treatment at the follow-up examination, serum UA was
      positively associated with changes in systolic (P=0.02) and diastolic pressure 4
      years later (P=0.04). In summary, serum UA level was an independent predictor of
      hypertension incidence and longitudinal BP progression at short-term follow-up in
      our community-based sample.

PMID- 15569853
TI  - Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study.
AB  - Uric acid has been proposed as an important risk factor in the development of
      primary hypertension in humans. However, limited information is available linking
      childhood uric acid levels and blood pressure levels in adulthood. This study
      examined 334 whites and 243 blacks enrolled in the Bogalusa Heart Study as
      children aged 5 to 17 years and as adults aged 18 to 35 years. The average follow
      up period was 12 years. Childhood uric acid was significantly correlated with
      childhood and adult blood pressure, both systolic and diastolic. In a
      multivariate regression analysis, adjusting for age, sex, race, childhood body
      mass index, childhood uric acid levels, and change in levels of uric acid were
      significant predictors of adult diastolic blood pressure, whereas change in uric
      acid was a significant predictor of adult systolic blood pressures. In
      conclusion, elevated childhood serum uric acid levels are associated with
      increased blood pressure beginning in childhood and higher blood pressure levels
      that persist into adulthood, in males and females, whites and blacks, suggesting
      that early elevations in serum uric acid levels may play a key role in the
      development of human hypertension.

PMID- 15569854
TI  - Decreased levels of cytochrome P450 2E1-derived eicosanoids sensitize renal
      arteries to constrictor agonists in spontaneously hypertensive rats.
AB  - We compared renal interlobar arteries of spontaneously hypertensive rats (SHR)
      and Wistar-Kyoto rats (WKY) in terms of cytochrome P450 (CYP) 4A and CYP2E1
      protein expression; levels of 20-HETE, 19-HETE, and 18-HETE; and responsiveness
      to phenylephrine in the absence and presence of N-methylsulfonyl-12,12
      dibromododec-11-enamide (DDMS; 30 mumol/L), a CYP4A inhibitor. Relative to data
      in WKY, arteries of SHR exhibited diminished (P<0.05) CYP2E1 and levels of 19
      HETE (66.7+/-6.0 versus 44.9+/-2.8 pmol/mg) and 18-HETE (13.8+/-1.6 versus 7.9+/
      0.5 pmol/mg), whereas CYP4A and 20-HETE levels (99.3+/-9.1 versus 98.9+/-12.8
      pmol/mg) were unchanged. Phenylephrine contracted vascular rings of SHR and WKY;
      the R(max) was similar in both strains, but SHR vessels were more sensitive as
      denoted by the lower (P<0.05) EC50 (0.28+/-0.07 versus 0.71+/-0.12 mumol/L). DDMS
      decreased 20-HETE and, to a lesser extent, 19-HETE, while increasing (P<0.05) the
      EC50 for phenylephrine by 475% and 54% in vessels of SHR and WKY, respectively.
      The desensitizing effect of DDMS was reversed by 20-HETE. Notably, the minimal
      concentration of 20-HETE that decreased the EC50 for phenylephrine in DDMS
      treated vessels was smaller in SHR (0.1 micromol/L) than WKY (10 micromol/L), and
      the sensitizing effect of 20-HETE was blunted (P<0.05) by the (R) stereoisomers
      of 19-HETE and 18-HETE. We conclude that the increased sensitivity to
      phenylephrine in arteries of SHR is attributable to a vasoregulatory imbalance
      produced by a deficit in vascular CYP2E1-derived products, most likely 19(R)-HETE
      and 18(R)-HETE, which condition amplification of the sensitizing action of 20
      HETE.

PMID- 15569855
TI  - Selective silencing of angiotensin receptor subtype 1a (AT1aR) by RNA
      interference.
AB  - Angiotensin II exerts its physiological effects by activating multiple subtypes
      of its receptor such as AT1a-, AT1b-, and AT2-receptors. Because of a high degree
      of similarity among these G-protein-coupled receptors, it has been difficult to
      assign diverse physiological actions of angiotensin II through these receptor
      subtypes. We have developed small interfering RNAs to selectively inhibit the
      expression of the AT1a receptor (AT1aR) subtype. A dsRNA, AT1 47, was found to be
      highly selective and efficient in reducing the levels of AT1aR subtype.
      Transfection of AT1aR-expressing CHO cells with dsRNA AT1 47 resulted in an 80%
      decrease in the AT1aR expression. In contrast, dsRNA AT1 47 showed no significant
      effects on both AT1bR and AT2R subtypes. Thus, AT1 47 provides us with a powerful
      tool to selectively silence this subtype of receptor to investigate its role in
      cardiovascular physiology.

PMID- 15569856
TI  - Signaling via the angiotensin-converting enzyme enhances the expression of
      cyclooxygenase-2 in endothelial cells.
AB  - Angiotensin-converting enzyme (ACE) inhibitors elicit outside-in signaling via
      ACE in endothelial cells. This involves the CK2-mediated phosphorylation of ACE
      on Ser1270 and the activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway,
      resulting in an enhanced endothelial ACE expression. Because cyclooxygenase-2
      (COX-2) expression is reported to be increased in subjects treated with ACE
      inhibitors, we determined the role of ACE signaling in this phenomenon and the
      transcription factors involved. In lungs from mice treated with the ACE inhibitor
      ramipril for 5 days, COX-2 expression was increased. A similar (1.5- to 2-fold)
      increase in COX-2 protein was detected in primary cultures of human endothelial
      cells treated with ramiprilat. In an endothelial cell line stably expressing
      human somatic ACE, ramiprilat increased COX-2 promoter activity, an effect not
      observed in ACE-deficient cells or cells expressing a nonphosphorylatable ACE
      mutant (S1270A). The ramiprilat-induced, ACE-dependent increase in COX-2
      expression and promoter activity (both 1.5- to 2-fold greater than control) was
      prevented by the inhibition of JNK. Ramiprilat significantly enhanced the DNA
      binding activity of activator protein-1 in cells expressing ACE but not S1270A
      ACE. Activator protein-1 decoy oligonucleotides prevented the ACE inhibitor
      induced increase in COX-2 promoter activity and protein expression. As a
      consequence of the ramiprilat-induced increase in COX-2 expression, prostacyclin
      and prostaglandin E2, but not thromboxane A2, production was increased and was
      inhibited by the COX-2 inhibitor celecoxib. These results indicate that ACE
      signaling may underlie the increase in COX-2 and prostacyclin levels in patients
      treated with ACE inhibitors.

PMID- 15569857
TI  - S-nitrosoalbumin-mediated relaxation is enhanced by ascorbate and copper: effects
      in pregnancy and preeclampsia plasma.
AB  - S-nitrosoalbumin (SNO-Alb) is a major reservoir of releasable nitric oxide (NO)
      in plasma. In preeclampsia, a pregnancy-specific disorder associated with
      endothelial dysfunction, we previously found significant elevations in plasma SNO
      Alb concentrations and decreased plasma ascorbate (Asc) levels. This increased
      SNO-Alb may result from low-plasma Asc if Asc, along with transition metals (eg,
      copper [Cu]) are necessary for release of NO from S-nitrosothiols. We propose
      that vasodilator effects of SNO-Alb, mediated by release of NO, are fully
      realized only when Asc/Cu availability is sufficient. Relaxation responses to SNO
      Alb or the control reduced human serum albumin (SH-Alb), and responses to pooled
      plasma from normal or preeclamptic pregnancies were examined in isolated mouse
      arteries. Arteries preconstricted with phenylephrine were exposed to SNO-Alb or
      SH-Alb at physiologically relevant concentrations. When free Cu was added in
      excess (10 mumol/L), NO release was not dependent on Asc. However, when Cu was
      added at lower (physiological) levels, NO release was dependent on Asc. The
      addition of Asc and Cu to SNO-Alb stimulated vasodilatory responses in isolated
      arteries >90%, whereas no change in the SH-Alb (5%) response was observed.
      Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1+/
      4.7%, whereas normal pregnancy plasma caused 11.9+/-4.2% relaxation (P=0.007).
      These data indicate that SNO-Alb alone or in plasma can act as a potent
      vasodilator, and that sufficient Asc/Cu promotes this action. We suggest that the
      higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a
      deficiency in Asc/Cu-mediated release of NO from SNO-Alb.

PMID- 15569858
TI  - Birth weight and blood pressure in childhood: results from the Health Survey for
      England.
AB  - Findings of previous reports relating low birth weight with raised blood pressure
      in childhood and adolescence have been inconsistent. The present study uses cross
      sectional data from a series of nationally representative annual surveys--the
      Health Survey for England--between 1995 and 2002, totaling a sample of 15 629
      children aged 5 to 15. A significant negative relationship between birth weight,
      in quartiles or dichotomized as low (<2.5 kg) and normal (> or =2.5 kg) and
      systolic blood pressure was apparent. Linear regression analyses confirmed these
      findings. When current weight was included in the model, the strength of the
      relationship increased. An interaction term between birth weight and current
      weight was not significant. A life-course plot for those aged 13 to 15 (n=3900),
      converting the weight measurements at birth and as a teenager to standard
      deviation scores to make the regression coefficients comparable, showed the
      importance of weight gain on blood pressure (1 standard deviation increase in
      weight from birth to age 13 to 15 was associated with an increase in systolic
      blood pressure of 0.8 mm Hg). Separating those with low and normal birth weight
      demonstrated that the increase in weight from birth to adolescence had an effect
      on blood pressure in both those with low and normal birth weight. Postnatal
      changes in size have a more important effect on blood pressure in childhood and
      adolescence than birth weight. Reducing the prevalence of overweight among
      children may reduce their systolic blood pressure importantly and, particularly
      among children with lower birth weight, the prevalence of hypertension later in
      life.

PMID- 15569859
TI  - Optimal threshold value for left ventricular hypertrophy in blacks: the
      Atherosclerosis Risk in Communities study.
AB  - The distribution of echocardiographic left ventricular (LV) mass differs among
      ethnicities. Because ethnic-specific echocardiographic criteria for LV
      hypertrophy (LVH) are not established, we determined whether threshold values
      derived from overwhelmingly white populations are appropriate for blacks, a
      subgroup having more LVH. Between 1992 and 1994, LV mass was measured
      echocardiographically in the Jackson, Mississippi, black cohort of the
      Atherosclerosis Risk in Communities study. Participants free of prevalent
      cardiovascular disease (CVD) (n=1616; mean+/-SD, age 59+/-5.7; 65% women and 57%
      with hypertension) were included. The optimal LVH threshold value was selected
      from the continuum of LV mass index (LVMI=LV mass/height(2.7)) using 3 methods:
      (1) the best operating point from the area under the resulting receiver-operating
      characteristic (ROC) curve predicting incident CVD; (2) the value with the
      smallest probability value associated with incident CVD; and (3) visual
      inspection of functions of LVMI and CVD in the general additive model (GAM) plot.
      At a median follow-up of 6.8 years, there were 192 events (coronary heart
      disease=87, stroke=62, and congestive heart failure=43; incidence=17.6/1000
      person-years). The best operating point from the resulting ROC analysis was 51.2
      g/m(2.7) for sensitivity (53.4%) and specificity (61.5%). The Cox and GAM models
      adjusted for age, gender, systolic blood pressure, hypertension, diabetes,
      smoking, total cholesterol-to-high-density lipoprotein ratio, LVH by ECG
      criterion, and socioeconomic status found 50 to 51 g/m(2.7) as the optimal
      threshold for LVH in middle-aged blacks, corresponding to a minimum probability
      value and to a log-hazard ratio of zero, respectively. Because these values are
      close to the 51 g/m(2.7) established from predominantly white populations, this
      cutpoint is appropriate for both groups.

PMID- 15569860
TI  - Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does
      not reduce blood markers of inflammation, endothelial dysfunction, or
      hypercoagulability in patients with previous transient ischemic attack or stroke:
      a randomized substudy of the VITATOPS trial.
AB  - BACKGROUND AND PURPOSE: Epidemiological and laboratory studies suggest that
      increasing concentrations of plasma homocysteine (total homocysteine [tHcy])
      accelerate cardiovascular disease by promoting vascular inflammation, endothelial
      dysfunction, and hypercoagulability. METHODS: We conducted a randomized
      controlled trial in 285 patients with recent transient ischemic attack or stroke
      to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg,
      and vitamin B6 25 mg compared with placebo on laboratory markers of vascular
      inflammation, endothelial dysfunction, and hypercoagulability. RESULTS: At 6
      months after randomization, there was no significant difference in blood
      concentrations of markers of vascular inflammation (high-sensitivity C-reactive
      protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction
      (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1
      [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin
      [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients
      assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI,
      2.7 to 4.7) reduction in total homocysteine (tHcy). CONCLUSIONS: Lowering tHcy by
      3.7 micromol/L with folic acid-based multivitamin therapy does not significantly
      reduce blood concentrations of the biomarkers of inflammation, endothelial
      dysfunction, or hypercoagulability measured in our study. The possible
      explanations for our findings are: (1) these biomarkers are not sensitive to the
      effects of lowering tHcy (eg, multiple risk factor interventions may be
      required); (2) elevated tHcy causes cardiovascular disease by mechanisms other
      than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of
      increased vascular risk.

PMID- 15569861
TI  - Optimizing discharge planning: clinical predictors of longer stay after
      recombinant tissue plasminogen activator for acute stroke.
AB  - BACKGROUND AND PURPOSE: The length of stay (LOS) is the main cost-determining
      factor for inpatients with acute stroke. Although studies have identified
      variables associated with LOS, few have analyzed predictors of longer stay after
      receiving thrombolytic therapy for acute stroke. METHODS: We studied all
      consecutive acute stroke patients receiving intravenous recombinant tissue
      plasminogen activator (rtPA) admitted to the London Health Sciences Center, in
      London, Ontario, Canada, from 1999 to 2003. Longer stay was defined as LOS > or
      =7 days after admission. Demographic as well as baseline clinical, laboratory,
      and imaging variables were analyzed to identify predictors of LOS. Significant
      variables were entered into a multivariate logistic regression analysis. RESULTS:
      Among 216 acute stroke patients receiving rtPA, the median LOS was 6 days. LOS
      was >7 days in 102 (49%) patients. Age > or =70 (odds ratio [OR], 2.2; 95% CI,
      1.2 to 4.0), lack of improvement at 24 hours (OR, 2.5; 95% CI, 1.4 to 4.4),
      prestroke modified Rankin Scale > or =2 (OR, 2.4; 95% CI, 1.2 to 4.9), baseline
      National Institutes of Health Stroke Scale score > or =15 (OR, 9.4; 95% CI, 3.2
      to 27.6), cortical involvement (OR, 2.2; 95% CI, 1.2 to 3.9), and new infarction
      on the control computed tomography (CT; OR, 2.8; 95% CI, 1.4 to 5.9) were
      independent predictors of longer stay. CONCLUSIONS: Lack of improvement at 24
      hours after rtPA, cortical involvement, and new infarction on the 24-hour CT scan
      are relevant variables that can independently affect the LOS. These new variables
      may be useful for establishing policy in relation to the organization and
      planning of the health care system.

PMID- 15569862
TI  - Impaired vascular mechanotransduction in a transgenic mouse model of CADASIL
      arteriopathy.
AB  - BACKGROUND AND PURPOSE: CADASIL is an inherited small-vessel disease responsible
      for lacunar strokes and cognitive impairment. The disease is caused by highly
      stereotyped mutations in Notch3, the expression of which is highly restricted to
      vascular smooth muscle cells (VSMCs). The underlying vasculopathy is
      characterized by degeneration of VSMCs and the accumulation of granular
      osmiophilic material (GOM) and Notch3 protein within the cell surface of these
      cells. In this study, we assessed early functional changes related to the
      expression of mutant Notch3 in resistance arteries. METHODS: Vasomotor function
      was examined in vitro in arteries from transgenic mice that express a mutant
      Notch3 in VSMC. Tail artery segments from transgenic and normal wild-type male
      mice were mounted on small-vessel arteriographs, and reactivity to mechanical
      (flow and pressure) forces and pharmacological stimuli were determined. Mice were
      studied at 10 to 11 months of age when VSMC degeneration, GOM deposits, and
      Notch3 accumulation were not yet present. RESULTS: Passive arterial diameter,
      contraction to phenylephrine, and endothelium-dependent relaxation to
      acetylcholine were unaffected in transgenic mice. By contrast, flow-induced
      dilation was significantly decreased and pressure-induced myogenic tone
      significantly increased in arteries from transgenic mice compared with wild-type
      mice. CONCLUSIONS: This is the first study to our knowledge providing evidence
      that mutant Notch3 impairs selectively the response of resistance arteries to
      flow and pressure. The data suggest an early role of vascular dysfunction in the
      pathogenic process of the disease.

PMID- 15569863
TI  - The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9
      hour window acute stroke thrombolysis trial with intravenous desmoteplase.
AB  - BACKGROUND AND PURPOSE: Most acute ischemic stroke patients arrive after the 3
      hour time window for recombinant tissue plasminogen activator (rtPA)
      administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose
      finding randomized trial designed to evaluate the safety and efficacy of
      intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic
      agent, administered within 3 to 9 hours of ischemic stroke onset in patients with
      perfusion/diffusion mismatch on MRI. METHODS: DIAS was a placebo-controlled,
      double-blind, randomized, dose-finding phase II trial. Patients with National
      Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of
      perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47
      (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg,
      37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic
      intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through
      62.5 microg/kg, 90 microg/kg, and 125 microg/kg were subsequently investigated in
      57 patients (referred to as Part 2). The safety endpoint was the rate of sICH.
      Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and
      clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index
      at 90 days. RESULTS: Part 1 was terminated prematurely because of high rates of
      sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH
      occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012)
      were observed with desmoteplase (125 microg/kg) compared with 19.2% with placebo.
      Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients
      and between 13.3% (62.5 microg/kg; P=0.757) and 60.0% (125 microg/kg; P=0.0090)
      of desmoteplase-treated patients. Early reperfusion correlated favorably with
      clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients
      experiencing reperfusion versus 24.6% of patients without reperfusion.
      CONCLUSIONS: Intravenous desmoteplase administered 3 to 9 hours after acute
      ischemic stroke in patients selected with perfusion/diffusion mismatch is
      associated with a higher rate of reperfusion and better clinical outcome compared
      with placebo. The sICH rate with desmoteplase was low, using doses up to 125
      microg/kg.

PMID- 15569864
TI  - Cognitive function before and after surgery in patients with unruptured
      intracranial aneurysm.
AB  - BACKGROUND AND PURPOSE: This prospective study investigated whether surgery for
      unruptured intracranial aneurysms (UIAs) affects cognitive function and cerebral
      blood flow (CBF). METHODS: Cognitive tests using the Wechsler Adult Intelligence
      Scale-Revised, Wechsler Memory Scale, Rey-Osterrieth Complex Figure test, and CBF
      measurements using single-photon emission computed tomography were performed
      before and after surgery for UIAs in 44 patients < or =70 years of age. RESULTS:
      Group-rate analysis showed the verbal intelligence quotient (IQ), performance IQ,
      full-scale IQ, and recall trial scores of the Rey-Osterrieth Complex Figure test
      all increased significantly after surgery, whereas the Wechsler Memory Scale and
      copy trial scores of the Rey-Osterrieth Complex Figure test were not
      significantly different. Event-rate analysis demonstrated that no patient showed
      impaired cognition. There was no significant difference between CBF before and
      after surgery. CONCLUSIONS: Surgical repair for UIAs does not impair cognition or
      CBF in patients without postoperative restrictions in lifestyle.

PMID- 15569865
TI  - Sex-based differences in response to recombinant tissue plasminogen activator in
      acute ischemic stroke: a pooled analysis of randomized clinical trials.
AB  - BACKGROUND AND PURPOSE: Women experience worse outcomes after stroke compared
      with men. Prior work has suggested sex-based differences in coagulation and
      fibrinolysis markers in subjects with acute stroke. We explored whether sex might
      modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes
      in patients with acute ischemic stroke. METHODS: Using a combined database
      including subjects from the National Institute of Neurological Disorders and
      Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in
      Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute
      Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients
      randomized to rtPA versus placebo by sex. We used logistic regression to control
      for potential confounders. RESULTS: Among 988 women treated between 0 and 6 hours
      from symptom onset, patients receiving rtPA were significantly more likely than
      those receiving placebo to have a modified Rankin Score < or =1 (40.5% versus
      30.3%, P<0.0008). Among 1190 men, the trend toward benefit in the overall group
      did not reach statistical significance (38.5% versus 36.7%, P=0.52). An
      unadjusted analysis showed that women were significantly more likely to benefit
      from rtPA compared with men (P=0.04). Controlling for age, baseline National
      Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time,
      prior stroke, systolic blood pressure, extent of hypoattenuation on baseline
      computed tomography scan and several significant interaction terms (including
      onset to treatment time-by-treatment and systolic blood pressure-by treatment)
      did not substantially change the strength of the interaction between gender and
      rtPA treatment (P=0.04). CONCLUSIONS: In this pooled analysis of rtPA in acute
      ischemic stroke, women benefited more than men, and the usual gender difference
      in outcome favoring men was not observed in the thrombolytic therapy group. For
      patients presenting at later time intervals, when the risks and benefits of rtPA
      are more finely balanced, sex may be an important variable to consider for
      patient selection.

PMID- 15569866
TI  - Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in
      acute cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: We routinely perform an urgent bedside neurovascular
      ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial
      Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the
      yield and accuracy of NVUE to identify lesions amenable for interventional
      treatment (LAITs). METHODS: NVUE was performed with portable carotid duplex and
      TCD using standardized fast-track (<15 minutes) insonation protocols. Digital
      subtraction angiography (DSA) was the gold standard for identifying LAIT. These
      lesions were defined as proximal intra- or extracranial occlusions, near
      occlusions, > or =50% stenoses or thrombus in the symptomatic artery. RESULTS:
      One hundred and fifty patients (70 women, mean age 66+/-15 years) underwent NVUE
      at median 128 minutes after symptom onset. Fifty-four patients (36%) received
      intravenous or intra-arterial thrombolysis (median National Institutes of Health
      Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS > or =10 points).
      NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of
      acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients
      with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30
      patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted
      LAIT presence with 100% sensitivity and 100% specificity, although individual
      accuracy parameters for TCD and carotid duplex specific to occlusion location
      ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no
      temporal windows. CONCLUSIONS: Bedside neurovascular ultrasound examination,
      combining carotid/vertebral duplex with TCD yields a substantial proportion of
      LAITs in excellent agreement with urgent DSA.

PMID- 15569867
TI  - Expression and function of recombinant S1179D endothelial NO synthase in human
      pial arteries.
AB  - BACKGROUND AND PURPOSE: Mutation of serine 1179 to aspartate on the endothelial
      NO synthase (eNOS) increases NO production in the absence of stimulation by
      agonists. The present study was designed to determine the effect of recombinant
      S1179DeNOS gene expression on the vasomotor function of human pial arteries.
      METHODS: Pial arteries were isolated from 28 patients undergoing temporal
      lobectomy for intractable seizures. Adenoviral vectors (10(10) pfu/mL) encoding
      beta-galactosidase (AdCMVLacZ) or S1179DeNOS (AdCMVS1179DeNOS) were used for ex
      vivo gene transfer, and vasomotor function was evaluated in control and
      transduced arteries. RESULTS: Contractions to cumulative additions of U46619 were
      not affected by expression of LacZ or S1179DeNOS. Endothelium-dependent
      relaxations to bradykinin or endothelium-independent relaxations to
      Diethylaminodiazen-1-ium-1,2-dioate were significantly reduced in arteries
      expressing S1179DeNOS. A superoxide dismutase mimetic, manganese (III) tetrakis
      (4-benzoic acid) porphyrin chloride, failed to improve the reduced relaxations to
      bradykinin. The levels of cGMP were significantly elevated in arteries expressing
      S1179DeNOS. CONCLUSIONS: Our results support the concept that high local
      production of NO in pial arterial wall causes adaptive reduction of vasodilator
      reactivity to NO.

PMID- 15569868
TI  - Heritability of carotid artery atherosclerotic lesions: an ultrasound study in
      154 families.
AB  - BACKGROUND AND PURPOSE: Ultrasound examination of the carotid arteries yields
      several quantitative measures that may serve as intermediate phenotypes in
      genetic studies. This study was undertaken to compare the heritabilities of 3
      ultrasound measures: intima-media thickness (IMT), plaque score, and maximal
      stenosis. METHODS: We studied 565 individuals from 154 families ascertained by an
      affected parent with carotid artery atherosclerosis. IMT, plaque score, and
      maximal stenosis of the carotid arteries were examined by B-mode ultrasound and
      analyzed quantitatively. Heritability estimates were obtained by variance
      component analysis as implemented in the program SOLAR (sequential oligogenic
      linkage analysis routines). Covariates were age, sex, weight, height, body mass
      index (BMI), arterial hypertension, diabetes mellitus, amount of nicotine
      consumed, and plasma levels of low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)],
      triglycerides, factor VIII, factor XIII, fibrinogen, and von Willebrand factor
      (vWF). RESULTS: After accounting for the covariables age, sex, hypertension,
      diabetes mellitus, and Lp(a), heritability of IMT was estimated as h2=0.61+/-0.17
      (P=0.001). Variation of plaque score was influenced by age, sex, hypertension,
      diabetes mellitus, hypercholesterolemia, amount of nicotine consumed, factor
      VIII, and vWF. When these were considered, no significant heritability could be
      detected. Heritability of stenosis was estimated as h2=0.47+/-0.07 (P=0.006),
      with age, sex, BMI, hypertension, diabetes mellitus, amount of nicotine consumed,
      and LDL/HDL ratio as covariates. CONCLUSIONS: Among the 3 ultrasound measures
      studied, IMT had the highest heritability. IMT was strongly influenced by genetic
      determinants other than those influencing known risk factors. This makes IMT a
      promising candidate for use as an intermediate phenotype in genetic studies
      aiming to identify novel genes for atherosclerosis.

PMID- 15569870
TI  - Impaired functional recovery after stroke in the stroke-prone spontaneously
      hypertensive rat.
AB  - BACKGROUND AND PURPOSE: To identify if the stroke-prone spontaneously
      hypertensive rat (SHRSP) exhibits impaired functional recovery after stroke
      compared with its normotensive reference strain, the Wistar Kyoto rat (WKY).
      METHODS: In study 1, a 2-mm distal middle cerebral artery occlusion (middle
      cerebral artery occlusion) was performed in both strains and recovery assessed
      using a 33-point neurological score. Because SHRSPs displayed much larger
      infarcts than WKYs, study 2 and study 3 involved extending the length of middle
      cerebral artery (MCA) occlusion in the WKY to increase the volume and
      distribution of infarction to comparable levels with SHRSP. Animals were assessed
      with the neurological score, tapered beam walk, and cylinder tests. RESULTS: In
      study 1, infarct volume (expressed as a percent of contralateral hemisphere) was
      WKY 13.1+/-3% and SHRSP 19.8+/-1%. Initial neurological deficit was greater (WKY
      25+/-1, SHRSP 22+/-1, out of a possible 33) and subsequent recovery was poorer in
      SHRSP. In studies 2 and 3, infarct volume and distribution (study 2, WKY 21.8+/
      1.3%, SHRSP 22.9+/-3%; study 3, WKY 17.2+/-2%, SHRSP 16.5+/-3%) and initial
      neurological deficit at 2 hours after middle cerebral artery occlusion (study 2
      WKY 23+/-1, SHRSP 22+/-2; study 3 WKY 25+/-1 and SHRSP 23+/-1; mean+/-SEM) were
      comparable between strains. However, whereas WKY recovered toward normal scores,
      SHRSP scored significantly lower 2 weeks (study 2) and 4 weeks (study 3) after
      middle cerebral artery occlusion. Beam walk data revealed long-term impairment in
      SHRSP contralateral limb use, compared with WKY, at days 3, 7, and 28 (P<0.05).
      CONCLUSIONS: SHRSP exhibit impaired functional recovery after stroke compared
      with WKY.

PMID- 15569871
TI  - Safety and feasibility of recombinant factor VIIa for acute intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Hematoma growth occurs in 38% of intracerebral hemorrhage
      (ICH) patients scanned by computed tomography (CT) within 3 hours of onset.
      Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of
      vascular injury and may minimize hematoma growth after ICH. METHODS: In this
      randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects
      with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or
      rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary
      endpoint was the frequency of adverse events (AEs). Safety assessments included
      serial electrocardiography (ECG), troponin I and coagulation testing, lower
      extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.
      RESULTS: Mean age was 61 years (range, 30 to 93) and 57% were male. At admission,
      mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to
      26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume
      was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes
      (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality
      11%). Six AEs were considered possibly treatment-related, including rash,
      vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis
      (placebo and 20-microg/kg groups). No myocardial ischemia, consumption
      coagulopathy, or dose-related increase in edema:ICH volume occurred. CONCLUSIONS:
      This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and
      raised no major safety concerns. Larger studies are justified to determine
      whether rFVIIa can safely and effectively limit ICH growth.

PMID- 15569872
TI  - Depressive symptoms and mortality in men: results from the Multiple Risk Factor
      Intervention Trial.
AB  - BACKGROUND AND PURPOSE: Depression may be a risk factor for cardiovascular
      disease (CVD) mortality. We evaluated long-term mortality risk associated with
      depressive symptoms measured at middle age among men at high risk for coronary
      heart disease (CHD). METHODS: 12,866 men without definite evidence of CHD at
      study entry but who had above average risk of CHD based on blood pressure, blood
      cholesterol levels, and/or cigarette smoking were recruited into the Multiple
      Risk Factor Intervention Trial (MRFIT). Survivors at the end of the trial were
      followed-up for mortality for an additional 18 years. Men who had completed the
      Center for Epidemiologic Studies Depression (CES-D) scale near the end of the
      trial (n=11,216) were used in a prospective analysis of post-trial all-cause and
      cause-specific mortality during 18-year follow-up after CES-D assessment.
      RESULTS: Greater depressive symptoms measured at the end of the trial were
      associated with significantly higher risk of all-cause mortality and for cause
      specific death, a higher risk of CVD, and, more specifically, stroke mortality
      (all P values <0.02) but not CHD mortality (P=0.48) in linear trend analyses. The
      significant associations were strongest for those reporting the greatest
      depression: hazard ratio (HR)=1.15 (95% CI, 1.03 to 1.28; P<0.01) for all-cause
      mortality for those in the highest depressive symptom quintile, HR=1.21 for CVD
      mortality (95% CI, 1.03 to 1.41; P<0.05), and HR=2.03 for stroke mortality (95%
      CI, 1.20 to 3.44; P<0.01) compared with those in the lowest quintile. These
      associations were adjusted for age, intervention group, race, educational
      attainment, smoking at baseline and visit 6, trial averaged systolic blood
      pressure, alcohol consumption, and fasting cholesterol, as well as the occurrence
      of nonfatal cardiovascular events during the trial. CONCLUSIONS: Greater
      depressive symptoms are associated with an increase in the risk of all-cause and,
      more specifically, CVD mortality in men. Stroke but not CHD was the form of CVD
      with which depressive symptoms were associated.

PMID- 15569873
TI  - Incidence, manifestations, and predictors of worsening white matter on serial
      cranial magnetic resonance imaging in the elderly: the Cardiovascular Health
      Study.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly
      commonly show white matter findings that may raise concerns. We sought to
      document incidence, manifestations, and predictors of worsening white matter
      grade on serial imaging. METHODS: The Cardiovascular Health Study is a population
      based, longitudinal study of 5888 people aged 65 years and older, of whom 1919
      have had extensive initial and follow-up evaluations, including 2 MRI scans
      separated by 5 years. Scans were read without clinical information in standard
      side-by-side fashion to determine worsening white matter grade. RESULTS:
      Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade.
      Although similar at initial scan, participants with worsening white matter grade,
      compared with those without, experienced greater decline on modified Mini-Mental
      State examination and Digit-Symbol Substitution test (both P< or =0.001) after
      controlling for potential confounding factors, including occurrence of transient
      ischemic attack or stroke between scans. Independent predictors of worsening
      white matter grade included cigarette smoking before initial scan and infarct on
      initial scan. Otherwise, predictors differed according to white matter grade on
      initial scan. For low initial grade, increased age, increased diastolic blood
      pressure, increased high-density lipoprotein cholesterol, and decreased low
      density lipoprotein cholesterol were associated with increased risk of worsening.
      For high initial grade, any cardiovascular disease and low ankle-arm index were
      associated with decreased risk of worsening, whereas use of diuretics and statins
      were associated with increased risk. CONCLUSIONS: Worsening white matter grade on
      serial MRI scans in elderly is common, is associated with cognitive decline, and
      has complex relations with cardiovascular risk factors.

PMID- 15569874
TI  - Combining insulin-like growth factor derivatives plus caffeinol produces robust
      neuroprotection after stroke in rats.
AB  - BACKGROUND AND PURPOSE: Insulin-like growth factor-1 (IGF-1) and caffeinol are
      both neuroprotective and probably have different mechanisms of action; therefore,
      they may be more effective in combination. METHODS: We tested the N-terminal
      tripeptide of IGF-1, Gly-Pro-Glu (GPE), and its analogue, G2MePE, alone and with
      caffeinol in a rat middle cerebral artery (MCA) suture occlusion model. We
      randomly assigned rats to 6 groups of 8 to 12 animals: (1) control; (2) GPE, 3
      mg/kg per hour; (3) G2MePE, 0.3 mg/kg per hour; (4) caffeinol, a mixture of
      caffeine (10 mg/kg) with ethanol (0.32 g/kg); (5) GPE with caffeinol (combination
      of group 2 with 4); and (6) G2MePE with caffeinol (combination of group 3 with
      4). Drugs were started 75 minutes after suture occlusion, at the start of
      reperfusion. Three days after MCA occlusion, neurological deficit (Neurological
      Deficit Score [NDS]) and lesion volume were measured. RESULTS: GPE and caffeinol
      improved NDS by 34% and 36%, respectively (P<0.01), and also decreased cortical
      but not striatal lesion volume compared with control (GPE cortex, 121 mm3;
      caffeinol cortex, 134 mm3; and control, 221 mm3; P<0.01). GPE plus caffeinol did
      not have more efficacy than either GPE or caffeinol alone. G2MePE slightly
      improved NDS (19.7%, P=0.05) but not lesion volume. However, G2MePE plus
      caffeinol very significantly improved NDS (64%) and lesion volume in both cortex
      (combination 95 mm3 versus control 221 mm3) and striatum (combination 74 mm3
      versus control 110 mm3) (P<0.001), and was significantly more effective than
      either caffeinol or G2MePE alone. CONCLUSIONS: Both GPE and caffeinol
      significantly protect cortex after MCA occlusion. At the doses used in this
      study, the GPE analogue G2MePE by itself had minimal protective effects, but when
      combined with caffeinol, it demonstrated robust beneficial effects on cortical
      and subcortical lesion size and behavioral deficit. Further study of this
      combination appears justified.

PMID- 15569875
TI  - Functional electrical stimulation improves motor recovery of the lower extremity
      and walking ability of subjects with first acute stroke: a randomized placebo
      controlled trial.
AB  - BACKGROUND AND PURPOSE: The effectiveness of functional electrical stimulation
      (FES) has been investigated in chronic hemiplegia. The present study examines
      whether FES, given during acute stroke, was more effective in promoting motor
      recovery of the lower extremity and walking ability than standard rehabilitation
      alone. METHODS: Forty-six subjects, 70.9+/-8.0 years old and 9.2+/-4.1 days after
      stroke, were assigned randomly to 1 of 3 groups receiving standard rehabilitation
      with FES or placebo stimulation or alone (control). FES was applied 30 minutes
      and placebo stimulation 60 minutes, 5 days per week for 3 weeks. Outcome
      measurements included composite spasticity score, maximum isometric voluntary
      contraction of ankle dorsi-flexors and planter-flexors, and walking ability. They
      were recorded before treatment, weekly during the 3-week treatment, and at week 8
      after stroke. RESULTS: No significant differences were found in the baseline
      measurements. After 3 weeks of treatment, there was a significant reduction in
      the percentage of composite spasticity score, and a significant improvement in
      the ankle dorsiflexion torque, accompanied by an increase in agonist
      electromyogram and a reduction in electromyogram cocontraction ratio in the FES
      group, when compared with the other 2 groups (P<0.05). All subjects in the FES
      group were able to walk after treatment, and 84.6% of them returned home, in
      comparison with the placebo (53.3%) and control (46.2%, P<0.05) groups.
      CONCLUSIONS: Fifteen sessions of FES, applied to subjects with acute stroke plus
      standard rehabilitation, improved their motor and walking ability to the degree
      that more subjects were able to return to home.

PMID- 15569876
TI  - The risk and benefit of endarterectomy in women with symptomatic internal carotid
      artery disease.
AB  - BACKGROUND AND PURPOSE: Perioperative risk and long-term benefit of carotid
      endarterectomy (CE) are not detailed in women with symptomatic internal carotid
      artery (ICA) stenosis. Our aim was to compare the efficacy of CE versus medical
      therapy in women and men with symptomatic ICA stenosis. METHODS: Data were taken
      from the North American Symptomatic Carotid Endarterectomy Trial (873 women, 2012
      men) and the ASA and Carotid Endarterectomy trial (335 women, 813 men). RESULTS:
      The 30-day perioperative risk of death was higher in women than in men (2.3%
      versus 0.8%, P=0.002). Higher perioperative risk of stroke and death was also
      observed (7.6% versus 5.9%) but not statistically significant. With > or =70%
      stenosis, the 5-year absolute risk reduction (ARR) in stroke from CE was similar
      between women (15.1%) and men (17.3%). With 50% to 69% stenosis, CE was not
      beneficial in women (ARR=3.0%, P=0.94), contrary to men (ARR=10.0%, P=0.02).
      Medically treated women had low risk for stroke. A stroke prognosis instrument
      (SPI-II) assigned points to 7 factors that identified higher risk for medically
      treated women: 3 points for hemispheric (not retinal) event, history of diabetes,
      previous stroke; 2 for age older than 70 years, stroke (not transient ischemic
      attack); 1 for severe hypertension, history of myocardial infarction. CE was
      beneficial only for 29.0% of women with 50% to 69% stenosis who had the highest
      total score of 8 to 15 (ARR=8.9%). CONCLUSIONS: Women and men with > or =70%
      symptomatic stenosis had similar long-term benefit from CE, although the
      perioperative risks were higher for women. CE was not beneficial for women with
      50% to 69% stenosis without other risk factors for stroke.

PMID- 15569877
TI  - Dipyridamole for preventing recurrent ischemic stroke and other vascular events:
      a meta-analysis of individual patient data from randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: Results from randomized controlled trials of
      dipyridamole, given with or without aspirin, for secondary prevention after
      ischemic stroke or transient ischemic attack (TIA) have given conflicting
      results. We performed a meta-analysis using individual patient data from relevant
      randomized controlled trials. METHODS: Randomized controlled trials involving
      dipyridamole in patients with previous ischemic stroke or TIA were sought from
      searches of the Cochrane Library, other electronic databases, references lists,
      earlier reviews, and contact with the manufacturer of dipyridamole. Individual
      patient data were merged from 5 of 7 relevant trials involving 11 459 patients.
      Results were adjusted for age, gender, qualifying event, and history of previous
      hypertension. RESULTS: Recurrent stroke was reduced by dipyridamole as compared
      with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and
      dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole
      alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to
      0.71). The point estimates obtained for the comparisons of aspirin and
      dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88;
      nonsignificant) were similar if the data from the largest trial, ESPS II (which
      provided 57% of data), were excluded. Similar findings were observed for nonfatal
      stroke. The combination of aspirin and dipyridamole also significantly reduced
      the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and
      vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97),
      dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95%
      CI, 0.57 to 0.75). Vascular death was not altered in any group. CONCLUSIONS:
      Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients
      with previous ischemic cerebrovascular disease. The combination of aspirin and
      dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial
      infarction, and vascular death as compared with aspirin alone.

PMID- 15569878
TI  - Docosahexaenoic acid complexed to albumin elicits high-grade ischemic
      neuroprotection.
AB  - BACKGROUND AND PURPOSE: High-dose human albumin therapy is strongly
      neuroprotective in models of brain ischemia and trauma and is currently being
      studied in a pilot-phase clinical stroke trial. Among its actions in ischemia,
      albumin induces the systemic mobilization of n-3 polyunsaturated fatty acids and
      may help to replenish polyunsaturated fatty acids lost from neural membranes.
      METHODS: We complexed 25% human albumin to docosahexaenoic acid (DHA; 22:6n-3)
      and compared its neuroprotective efficacy with that of native albumin in rats
      with 2-hour focal ischemia produced by intraluminal suture-occlusion of the
      middle cerebral artery. RESULTS: In animals treated with DHA-albumin, 0.63 g/kg,
      the improvement in neurobehavioral scores at 72 hours significantly exceeded that
      of other treatment groups, and the extent of histological protection (86%
      reduction in cortical infarction) was highly significant and tended to surpass
      the degree of cortical protection produced by native albumin at 1.25 g/kg (65%).
      DHA-albumin 0.63 g/kg, but not native albumin, also significantly reduced
      subcortical infarction and markedly diminished brain swelling. Lipidomic analysis
      of DHA-albumin-treated postischemic brains revealed a large accumulation of the
      neuroprotective DHA metabolite, 10,17S-docosatriene, in the ipsilateral
      hemisphere. CONCLUSIONS: The high-grade neuroprotection afforded by the DHA
      albumin complex at relatively low albumin doses is clinically advantageous in
      that it might reduce the likelihood of acute intravascular volume overload and
      congestive heart failure sometimes induced when patients with compromised
      cardiovascular function are treated with high-dose albumin.

PMID- 15569880
TI  - Stroke unit care and outcome: results from the 2001 National Sentinel Audit of
      Stroke (England, Wales, and Northern Ireland).
AB  - BACKGROUND AND PURPOSE: Stroke unit care is one of the most powerful
      interventions available to help stroke patients. There are limited data available
      to assess the impact of stroke units in routine clinical practice outside
      randomized clinical trials. This article uses data from the 2001 to 2002 National
      Stroke Audit to assess the effectiveness of stroke unit care in England, Wales,
      and Northern Ireland in delivering effective processes of care and in reducing
      case fatality and disability. METHODS: An observational study of the
      organization, structure, process of care, and outcomes for stroke in 2001. Case
      fatality after stroke in England was compared using data from the audit and
      routinely collected data from the Department of Health. 240 hospitals (196
      Trusts) from England, Wales, and Northern Ireland took part in the 2001 to 2002
      National Stroke Audit, a response rate of >95%. These sites assessed a total of
      8200 patients using the Royal College of Physicians Intercollegiate Working Party
      Stroke Audit Tool. RESULTS: The availability of stroke unit care varies hugely
      across the country. Case fatality after stroke was higher in Trusts with least
      availability of stroke unit care. These differences persisted after control for
      case mix. The process of care was better for patients managed on stroke units
      compared with other settings. Overall, the risk of death for patients who
      received stroke unit care was estimated to be approximately 75% that of the risk
      for those having no stroke unit care (95% CI, 60 to 90). CONCLUSIONS: Stroke unit
      care as provided in routine clinical practice in England, Wales, and Northern
      Ireland reduces case fatality by approximately 25%, which is in line with the
      figures obtained from systematic analysis of stroke unit trial data.

PMID- 15569881
TI  - Noninvasive detection of steno-occlusive disease of the supra-aortic arteries
      with three-dimensional contrast-enhanced magnetic resonance angiography: a
      prospective, intra-individual comparative analysis with digital subtraction
      angiography.
AB  - BACKGROUND AND PURPOSE: Concomitant disease of the supra-aortic arteries can
      influence the outcome of surgical treatment of carotid artery stenosis. However,
      sensitivity and specificity data of noninvasive contrast-enhanced 3-dimensional
      (3D) magnetic resonance angiography (CE MRA) for the detection of steno-occlusive
      disease of the entire supra-aortic arteries including the circle of Willis remain
      unclear. We aimed to intra-individually compare high-spatial-resolution CE 3D MRA
      and digital subtraction angiography (DSA) for the assessment of steno-occlusive
      vascular disease of the supra-aortic arteries. METHODS: CE MRA and DSA of the
      supra-aortic arteries were prospectively performed in 50 consecutive patients.
      Intra-individual comparison of CE MRA and DSA was available in 833 arteries. High
      spatial-resolution CE MRA comprised a measured voxel size of 0.81 mm x 0.81 mm x
      1 mm (0.66 mm3). Steno-occlusive vascular disease of the 833 arteries was
      assessed independently by 2 radiologists according to the NASCET criteria.
      RESULTS: CE MRA had a sensitivity of 100% (73/73), a specificity of 99.3%
      (760/765), a positive predictive value of 93.6% (73/78), and a negative
      predictive value of 100% (760/760) by using a 70% to 99% threshold of arterial
      diameter stenosis. For detection of occlusion, sensitivity, specificity, PPV, and
      NPV value of CE MRA were 100%, respectively. CONCLUSIONS: Noninvasive high
      spatial-resolution CE MRA is suited to replace diagnostic DSA for the detection
      of steno-occlusive disease of the supra-aortic arteries.

PMID- 15569882
TI  - On the "infallibility" of psychopathology and its implications for action.

PMID- 15569883
TI  - Cost-utility analysis studies of depression management: a systematic review.
AB  - OBJECTIVE: Depression is common, costly, treatable, and a major influence on
      quality of life. Cost-utility analysis combines costs with quantity and quality
      of life into a metric that is meaningful for studies of interventions or care
      strategies and is directly comparable to measures in other such studies. The
      objectives of this study were to identify published cost-utility analyses of
      depression screening, pharmacologic treatment, nonpharmacologic therapy, and care
      management; to summarize the results of these studies in an accessible format; to
      examine the analytic methods employed; and to identify areas in the depression
      literature that merit cost-utility analysis. METHOD: The authors selected
      articles regarding cost-utility analysis of depression management from the
      Harvard Center for Risk Analysis Cost-Effectiveness Registry. Characteristics of
      the publications, including study methods and analysis, were examined. Cost
      utility ratios for interventions were arranged in a league table. RESULTS: Of the
      539 cost-utility analyses in the registry, nine (1.7%) were of depression
      management. Methods for determining utilities and the source of the data varied.
      Markov models or cohort simulations were the most common analytic techniques.
      Pharmacologic interventions generally had lower costs per quality-adjusted life
      year than nonpharmacologic interventions. Psychotherapy alone, care management
      alone, and psychotherapy plus care management all had lower costs per quality
      adjusted life year than usual care. Depression screening and treatment appeared
      to fall within the cost-utility ranges accepted for common nonpsychiatric medical
      conditions. CONCLUSIONS: There is a paucity of literature on cost-utility
      analysis of depression management. High-quality cost-utility analysis should be
      considered for further research in depression management.

PMID- 15569884
TI  - The Hamilton Depression Rating Scale: has the gold standard become a lead weight?
AB  - OBJECTIVE: The Hamilton Depression Rating Scale has been the gold standard for
      the assessment of depression for more than 40 years. Criticism of the instrument
      has been increasing. The authors review studies published since the last major
      review of this instrument in 1979 that explicitly examine the psychometric
      properties of the Hamilton depression scale. The authors' goal is to determine
      whether continued use of the Hamilton depression scale as a measure of treatment
      outcome is justified. METHOD: MEDLINE was searched for studies published since
      1979 that examine psychometric properties of the Hamilton depression scale.
      Seventy studies were identified and selected, and then grouped into three
      categories on the basis of the major psychometric properties examined
      reliability, item-response characteristics, and validity. RESULTS: The Hamilton
      depression scale's internal reliability is adequate, but many scale items are
      poor contributors to the measurement of depression severity; others have poor
      interrater and retest reliability. For many items, the format for response
      options is not optimal. Content validity is poor; convergent validity and
      discriminant validity are adequate. The factor structure of the Hamilton
      depression scale is multidimensional but with poor replication across samples.
      CONCLUSIONS: Evidence suggests that the Hamilton depression scale is
      psychometrically and conceptually flawed. The breadth and severity of the
      problems militate against efforts to revise the current instrument. After more
      than 40 years, it is time to embrace a new gold standard for assessment of
      depression.

PMID- 15569885
TI  - Frontal cortex function.

PMID- 15569886
TI  - Narcolepsy with cataplexy.

PMID- 15569888
TI  - Impaired GABA neuronal response to acute benzodiazepine administration in panic
      disorder.
AB  - OBJECTIVE: Disturbances in the metabolism of the brain amino acid transmitter
      gamma-aminobutyric acid (GABA) may contribute to the pathophysiology of human
      anxiety disorders. Animal studies indicate that deletions or reductions in the
      expression of the gene for the GABA synthetic enzyme, glutamate decarboxylase 65
      (GAD(65)), reduce basal cortical GABA levels or stress-induced release of GABA in
      the cerebral cortex and increase fear behaviors. Complementing these findings,
      the authors recently observed lower than normal cortical GABA levels in patients
      with panic disorder. In the current study, the authors tested the hypothesis that
      panic disorder patients have a deficient GABA neuronal response to benzodiazepine
      (clonazepam) administration. METHOD: In a parallel-group, repeated-measures
      design, occipital cortex GABA responses to acute oral, open-label benzodiazepine
      administration were tested in 10 panic disorder patients and nine healthy
      comparison subjects. Occipital cortex total GABA levels were measured before and
      after medication administration by means of a novel proton magnetic resonance
      spectroscopic technique. RESULTS: Panic disorder patients had a deficient GABA
      neuronal response (blunted reduction of occipital cortex GABA level) to acute
      benzodiazepine administration, compared to the healthy subjects, who exhibited a
      significant decrease in occipital cortex GABA levels after this intervention. The
      patients also appeared to have persistently low occipital cortex GABA after
      chronic benzodiazepine treatment. CONCLUSIONS: Overall, these data are consistent
      with the hypothesis that a trait-like abnormality in GABA neuronal function
      contributes to the pathogenesis of human panic disorder. The data raise the
      possibility that GAD(65) enzyme dysfunction could be a pathogenic factor in panic
      disorder.

PMID- 15569889
TI  - Hippocampal volume in adult burn patients with and without posttraumatic stress
      disorder.
AB  - OBJECTIVE: Increasing evidence suggests that posttraumatic stress disorder (PTSD)
      is associated with small hippocampal size. The authors compared trauma-exposed
      subjects with PTSD and trauma-exposed subjects without PTSD to clarify whether
      small hippocampal size is related to PTSD or to mere trauma exposure. METHOD:
      Three-dimensional structural magnetic resonance imaging was used to assess
      hippocampal volumes in 30 men who had recently been exposed to a severe burn
      trauma and 15 matched healthy comparison subjects. RESULTS: Relative to the
      comparison subjects, the trauma-exposed subjects with PTSD (N=15) as well as the
      trauma-exposed subjects without PTSD (N=15) had significantly smaller volumes of
      the right hippocampus (subjects with PTSD: -12%; subjects without PTSD: -13%).
      Larger total areas of burned body surface were significantly related to smaller
      left hippocampal volumes. Use of analgesic/sedative treatment with the N-methyl-d
      aspartic acid (NMDA) antagonist ketamine was significantly related to larger
      right hippocampal volumes and to stronger PTSD symptoms. CONCLUSIONS: PTSD is not
      a necessary condition for small hippocampal size in trauma-exposed individuals.
      Rather, the results provide evidence that smaller hippocampal size in trauma
      exposed individuals is a result of traumatic stress. The posttraumatic
      application of NMDA antagonists may protect against hippocampal damage induced by
      traumatic stressors but increases the patient's risk of developing PTSD symptoms.

PMID- 15569890
TI  - Enhanced dopamine transporter density in psychotropic-naive patients with
      obsessive-compulsive disorder shown by [123I]{beta}-CIT SPECT.
AB  - OBJECTIVE: The authors examine the functional anatomy of serotonergic and
      dopaminergic systems in obsessive-compulsive disorder in psychotropic-naive
      patients without comorbidity. METHOD: [(123)I]beta-CIT binding patterns for
      dopamine and serotonin transporters in the brain were measured in 15 psychotropic
      naive adult outpatients with OCD (no comorbidity) and in 15 pairwise-matched
      healthy subjects. Volumes of interest were constructed on magnetic resonance
      imaging scans and coregistered with single photon emission computed tomography
      scans. Binding ratios were compared, and possible correlations between binding
      patterns and obsessive-compulsive symptoms were assessed. RESULTS: There were
      significant differences between patients and healthy subjects in the [(123)I]beta
      CIT binding pattern for dopamine transporter in the left caudate and left
      putamen. Patients had higher binding ratios than healthy subjects. No differences
      were found in the less specific [(123)I]beta-CIT binding pattern for serotonin
      transporters in the selected volumes of interest. Hemispheric within-group
      comparisons revealed no asymmetry effects. CONCLUSIONS: The results of our study
      provide direct evidence for an involvement of the dopaminergic system in the
      pathophysiology of OCD.

PMID- 15569891
TI  - Panic attack as a risk factor for severe psychopathology.
AB  - OBJECTIVE: The purpose of the study was to examine the relationship between panic
      attack and the onset of specific mental disorders and severe psychopathology
      across the diagnostic spectrum among adolescents and young adults. METHOD: Data
      were drawn from the Early Developmental Stages of Psychopathology Study
      (N=3,021), a 5-year prospective longitudinal study of psychopathology among
      youths ages 14-24 years at baseline in the community. Multiple logistic
      regression analyses were used to examine the associations between panic attacks
      at baseline, comorbid mental disorders in adolescence, and the risk of mental
      disorders across the diagnostic spectrum at follow-up. RESULTS: The large
      majority of subjects with panic attacks at baseline developed at least one DSM-IV
      mental disorder at baseline (89.4% versus 52.8% of subjects without panic
      attacks). Subjects with panic attacks at baseline had significantly higher
      baseline levels of any anxiety disorder (54.6% versus 25.0%), any mood disorder
      (42.7% versus 15.5%), and any substance use disorder (60.4% versus 27.5%),
      compared to subjects without panic attacks at baseline. Preexisting panic attacks
      significantly increased the risk of onset of any anxiety disorder, social phobia,
      specific phobia, generalized anxiety disorder, any substance use disorder, and
      any alcohol use disorder at follow-up in young adulthood, and these associations
      persisted after adjustment for all comorbid mental disorders assessed at
      baseline. More than one-third (37.6% versus 9.8%) of the subjects with panic
      attack at baseline met the criteria for at least three mental disorders at follow
      up during young adulthood. CONCLUSIONS: Panic attacks are associated with
      significantly increased odds of mental disorders across the diagnostic spectrum
      among young persons and appear to be a risk factor for the onset of specific
      anxiety and substance use disorders. Investigation of key family, environmental,
      and individual factors associated with the onset of panic attacks, especially in
      youth, may be an important direction for future research.

PMID- 15569892
TI  - Comorbidity of anxiety disorders with anorexia and bulimia nervosa.
AB  - OBJECTIVE: A large and well-characterized sample of individuals with anorexia
      nervosa and bulimia nervosa from the Price Foundation collaborative genetics
      study was used to determine the frequency of anxiety disorders and to understand
      how anxiety disorders are related to state of eating disorder illness and age at
      onset. METHOD: Ninety-seven individuals with anorexia nervosa, 282 with bulimia
      nervosa, and 293 with anorexia nervosa and bulimia were given the Structured
      Clinical Interview for DSM-IV Axis I Disorders and standardized measures of
      anxiety, perfectionism, and obsessionality. Their ratings on these measures were
      compared with those of a nonclinical group of women in the community. RESULTS:
      The rates of most anxiety disorders were similar in all three subtypes of eating
      disorders. About two-thirds of the individuals with eating disorders had one or
      more lifetime anxiety disorder; the most common were obsessive-compulsive
      disorder (OCD) (N=277 [41%]) and social phobia (N=134 [20%]). A majority of the
      participants reported the onset of OCD, social phobia, specific phobia, and
      generalized anxiety disorder in childhood, before they developed an eating
      disorder. People with a history of an eating disorder who were not currently ill
      and never had a lifetime anxiety disorder diagnosis still tended to be anxious,
      perfectionistic, and harm avoidant. The presence of either an anxiety disorder or
      an eating disorder tended to exacerbate these symptoms. CONCLUSIONS: The
      prevalence of anxiety disorders in general and OCD in particular was much higher
      in people with anorexia nervosa and bulimia nervosa than in a nonclinical group
      of women in the community. Anxiety disorders commonly had their onset in
      childhood before the onset of an eating disorder, supporting the possibility they
      are a vulnerability factor for developing anorexia nervosa or bulimia nervosa.

PMID- 15569893
TI  - Anxiety disorder comorbidity in bipolar disorder patients: data from the first
      500 participants in the Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD).
AB  - OBJECTIVE: The authors provide a detailed perspective on the correlates of
      comorbid anxiety in a large, well-characterized sample of bipolar disorder
      patients. METHOD: Anxiety and its correlates were examined in a cross-sectional
      sample from the first 500 patients with bipolar I or bipolar II disorder enrolled
      in the Systematic Treatment Enhancement Program for Bipolar Disorder, a
      multicenter project funded by the National Institute of Mental Health designed to
      evaluate the longitudinal outcome of patients with bipolar disorder. RESULTS:
      Lifetime comorbid anxiety disorders were common, occurring in over one-half of
      the sample, and were associated with younger age at onset, decreased likelihood
      of recovery, poorer role functioning and quality of life, less time euthymic, and
      greater likelihood of suicide attempts. Although substance abuse disorders were
      particularly prevalent among patients with anxiety disorders, comorbid anxiety
      appeared to exert an independent, deleterious effect on functioning, including
      history of suicide attempts (odds ratio=2.45, 95% CI=1.4-4.2). CONCLUSIONS: An
      independent association of comorbid anxiety with greater severity and impairment
      in bipolar disorder patients was demonstrated, highlighting the need for greater
      clinical attention to anxiety in this population, particularly for enhanced
      clinical monitoring of suicidality. In addition, it is important to determine
      whether effective treatment of anxiety symptoms can lessen bipolar disorder
      severity, improve response to treatment of manic or depressive symptoms, or
      reduce suicidality.

PMID- 15569894
TI  - Quality of care for primary care patients with anxiety disorders.
AB  - OBJECTIVE: This study evaluated quality of care for primary care patients with
      anxiety disorders in university-affiliated outpatient clinics in Los Angeles, San
      Diego, and Seattle. METHOD: Three hundred sixty-six primary care outpatients who
      were diagnosed with panic disorder, generalized anxiety disorder, social phobia,
      and/or posttraumatic stress disorder (with or without major depression) were
      surveyed about care received in the prior 3 months. Quality indicators were
      mental health referral, anxiety counseling, and use of appropriate antianxiety
      medication during the previous 3 months. RESULTS: Approximately one-third of
      patients with anxiety disorders had received counseling from their primary care
      provider in the prior 3 months. Fewer than 10% had receiving counseling from a
      mental health professional that included multiple elements of cognitive behavior
      therapy. Approximately 40% had received appropriate antianxiety medications in
      the previous 3 months, although only 25% had received them at a minimally
      adequate dose and duration. Overall, fewer than one in three patients had
      received either psychotherapy or pharmacotherapy that met a criterion for quality
      care. In multivariate analyses, patients with comorbid depression and/or medical
      illness were more likely-and patients from ethnic minorities were less likely-to
      receive appropriate antianxiety medications. CONCLUSIONS: Rates of quality care
      for anxiety disorders are moderate to low in university-affiliated primary care
      practices. Although an appropriate type of pharmacotherapy was frequently used,
      it was often of inadequate duration. Cognitive behavior therapy was markedly
      underused. These findings emphasize the need for practice guidelines and
      implementation of quality improvement programs for anxiety disorders in primary
      care.

PMID- 15569895
TI  - A longitudinal evaluation of the relationship between reproductive status and
      mood in perimenopausal women.
AB  - OBJECTIVE: Mood and reproductive function were prospectively evaluated in
      asymptomatic premenopausal women to determine whether the onset of depression was
      temporally linked to the perimenopause. METHOD: Twenty-nine asymptomatic,
      regularly cycling women were monitored longitudinally for an average of 5 years
      until at least 6 months of amenorrhea occurred. Outcome measures included mood
      ratings and menstrual diaries completed daily, the Structured Clinical Interview
      for DSM-IV, and plasma levels of follicle-stimulating hormone obtained at 3-6
      month intervals. The number of episodes of depression and their timing relative
      to the final menstrual period were determined. Differences in outcome measures
      between women who did and did not become depressed during the perimenopause were
      determined by Student's t test, chi-square tests, and Fisher's exact test.
      RESULTS: The authors observed 11 episodes of new-onset depression in nine of the
      29 women. In the 24 months surrounding the last menstrual period nine episodes of
      depression were observed. Six of the nine women who became depressed during the
      study had no prior depressive episodes. For the 24 months surrounding the final
      menses, the risk for onset of depression was 14 times as high as for a 31-year
      premenopausal period of time. Women who developed depression during the
      perimenopause were not distinguished from those who remained asymptomatic on the
      basis of symptom profile, duration of the perimenopause, endocrine measures, or
      past historical variables. CONCLUSIONS: These preliminary data suggest that
      events related to the late perimenopause may be associated with an increased
      susceptibility to develop depression in some women.

PMID- 15569896
TI  - Regional brain activity in women grieving a romantic relationship breakup.
AB  - OBJECTIVE: Separation from loved ones commonly leads to grief reactions. In some
      individuals, grief can evolve into a major depressive episode. The brain regions
      involved in grief have not been specifically studied. The authors studied brain
      activity in women actively grieving a recent romantic relationship breakup. It
      was hypothesized that while remembering their ex-partner, subjects would have
      altered brain activity in regions identified in sadness imaging studies: the
      cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal
      cortex. METHOD: Nine right-handed women whose romantic relationship ended within
      the preceding 4 months were studied. Subjects were scanned using blood-oxygen
      level-dependent functional magnetic resonance imaging while they alternated
      between recalling a sad, ruminative thought about their loved one (grief state)
      and a neutral thought about a different person they knew an equally long time.
      RESULTS: Acute grief (grief minus neutral state) was associated with increased
      group activity in posterior brain regions, including the cerebellum, posterior
      brainstem, and posterior temporoparietal and occipital brain regions. Decreased
      activity was more prominent anteriorly and on the left and included the anterior
      brainstem, thalamus, striatum, temporal cortex, insula, and dorsal and ventral
      anterior cingulate/prefrontal cortex. When a more lenient statistical threshold
      for regions of interest was used, additional increases were found in the lateral
      temporal cortex, supragenual anterior cingulate/medial prefrontal cortex, and
      right inferomedial dorsolateral prefrontal cortex, all of which were adjacent to
      spatially more prominent decreases. In nearly all brain regions showing brain
      activity decreases with acute grief, activity decreases were greater in women
      reporting higher grief levels over the past 2 weeks. CONCLUSIONS: During acute
      grief, subjects showed brain activity changes in the cerebellum, anterior
      temporal cortex, insula, anterior cingulate, and prefrontal cortex, consistent
      with the hypothesis. Subjects with greater baseline grief showed greater
      decreases in all these regions except for the cerebellum. Further imaging studies
      are needed to understand the relationship between normal sadness, grief, and
      depression.

PMID- 15569897
TI  - Depression among surviving caregivers: does length of hospice enrollment matter?
AB  - OBJECTIVE: Many terminally ill patients enroll in a hospice late in their
      illness, and recent data indicate decreasing lengths of hospice enrollment, yet
      we know little about the impact of hospice enrollment length on surviving
      caregivers. This is the first study the authors know of that examines the
      association between hospice enrollment length and subsequent major depressive
      disorder among surviving caregivers. METHOD: The authors conducted a prospective
      cohort study with 174 primary family caregivers of consecutively enrolled hospice
      patients with cancer between October 1999 and September 2001. Using data from in
      person interviews at the time of enrollment and 6-8 months after the patient's
      death, they estimated with logistic regression the adjusted risk of major
      depressive disorder with the Structured Clinical Interview for the DSM-IV axis I
      modules based on the number of days of hospice care before death. RESULTS:
      Caregivers of patients enrolled with hospice for 3 or fewer days were
      significantly more likely to have major depressive disorder at the follow-up
      interview than caregivers of those with longer hospice enrollment (24.1% versus
      9.0%, respectively), adjusted for baseline major depressive disorder and other
      potential confounders. CONCLUSIONS: The findings identify a target group for whom
      bereavement services might be most needed. The authors also suggest that earlier
      hospice enrollment may help reduce the risk of major depressive disorder during
      the first 6-8 months of bereavement, which raises concerns about recent trends
      toward decreasing lengths of hospice enrollment before death.

PMID- 15569898
TI  - Hippocampal volume and first major depressive episode after cancer diagnosis in
      breast cancer survivors.
AB  - OBJECTIVE: Patients experiencing their first major depressive episode after
      receiving a diagnosis of cancer are frequently seen in clinical oncology
      settings; however, little is known about the neurobiological basis of the first
      episode. In previous studies, a smaller hippocampus than in healthy comparison
      subjects has been observed in patients with a history of recurrent and prolonged
      major depressive episodes. The purpose of the present study was to investigate
      whether there is an association between hippocampal volume and a first major
      depressive episode after cancer diagnosis in cancer survivors. METHOD: The
      subjects were 68 female cancer survivors who had undergone breast cancer surgery
      3 or more years earlier (mean interval=4.3 years, SD=0.9). The hippocampal volume
      and delayed recall function of the 17 cancer survivors who had their first major
      depressive episode after receiving their cancer diagnosis and the 51 with no
      history of major depressive episode at any time during their lives were measured
      by magnetic resonance imaging and the Wechsler Memory Scale-Revised,
      respectively. RESULTS: The mean duration of the major depressive episode after
      cancer diagnosis was 11.9 weeks (SD=14.2). There were no significant differences
      in left or right hippocampal volume or in delayed recall function between the
      cancer survivors with and without a major depressive episode after cancer
      diagnosis. CONCLUSIONS: First major depressive episodes after cancer diagnosis in
      female cancer survivors do not appear to be associated with hippocampal volume.
      However, a longitudinal study with healthy comparison subjects is needed to draw
      a definite conclusion.

PMID- 15569899
TI  - Childhood trauma, dissociation, and psychiatric comorbidity in patients with
      conversion disorder.
AB  - OBJECTIVE: The aim of this study was to evaluate dissociative disorder and
      overall psychiatric comorbidity in patients with conversion disorder. METHOD:
      Thirty-eight consecutive patients previously diagnosed with conversion disorder
      were evaluated in two follow-up interviews. The Structured Clinical Interview for
      DSM-III-R, the Dissociation Questionnaire, the Somatoform Dissociation
      Questionnaire, and the Childhood Trauma Questionnaire were administered during
      the first follow-up interview. The Structured Clinical Interview for DSM-IV
      Dissociative Disorders was conducted in a separate evaluation. RESULTS: At least
      one psychiatric diagnosis was found in 89.5% of the patients during the follow-up
      evaluation. Undifferentiated somatoform disorder, generalized anxiety disorder,
      dysthymic disorder, simple phobia, obsessive-compulsive disorder, major
      depression, and dissociative disorder not otherwise specified were the most
      prevalent psychiatric disorders. A dissociative disorder was seen in 47.4% of the
      patients. These patients had dysthymic disorder, major depression, somatization
      disorder, and borderline personality disorder more frequently than the remaining
      subjects. They also reported childhood emotional and sexual abuse, physical
      neglect, self-mutilative behavior, and suicide attempts more frequently.
      CONCLUSIONS: Comorbid dissociative disorder should alert clinicians for a more
      chronic and severe psychopathology among patients with conversion disorder.

PMID- 15569900
TI  - Predictors of premature termination of inpatient treatment for anorexia nervosa.
AB  - OBJECTIVE: The authors examined predictors of premature dropout from a voluntary
      specialized inpatient treatment program for anorexia nervosa. METHOD: One hundred
      sixty-six consecutive patients with anorexia nervosa received an admission
      assessment that consisted of a diagnostic interview and psychometric measures of
      core eating pathology and associated psychopathology. Survival analysis was used
      to examine the rate, timing, and prediction of dropout. Predictors included a
      variety of clinical, demographic, and psychometric variables. RESULTS: Compared
      with program completers, program dropouts were more likely to have the binge
      eating/purging type of anorexia nervosa (65% versus 26%), had lower restraint
      scores, and reported more intense maturity fears and concerns about weight.
      CONCLUSIONS: Patients with the binge eating/purging type of anorexia nervosa are
      significantly less likely to complete inpatient treatment for the disorder.

PMID- 15569901
TI  - The volume-quality relationship of mental health care: does practice make
      perfect?
AB  - OBJECTIVE: An extensive literature has demonstrated a relationship between
      hospital volume and outcomes for surgical care and other medical procedures. The
      authors examined whether an analogous association exists between the volume of
      mental health delivery and the quality of mental health care. METHOD: The study
      used data for the 384 health maintenance organizations participating in the
      Health Employer Data and Information Set (HEDIS), covering 73 million enrollees
      nationwide. Analyses examined the association between three measures of mental
      health volume (total annual ambulatory visits, inpatient discharges, and
      inpatient days) and the five HEDIS measures of mental health performance (two
      measures of follow-up after psychiatric hospitalization and three measures of
      outpatient antidepressant management), with adjustment for plan and enrollee
      characteristics. RESULTS: Plans in the lowest quartile of outpatient and
      inpatient mental health volume had an 8.45 (95% CI [confidence interval]=4.97
      14.37) to 21.09 (95% CI=11.32-39.28) times increase in odds of poor 7- and 30-day
      follow-up after discharge from inpatient psychiatric hospitalization. Low-volume
      plans had a 3.49 (95% CI=2.15-5.67) to 5.42 (95% CI=3.21-9.15) times increase in
      odds of poor performance on the acute, continuation, and provider measures of
      antidepressant treatment. CONCLUSIONS: The large and consistent association
      between mental health volume and performance suggests parallels with the medical
      and surgical literature. As with that previous literature, further work is needed
      to better understand the mechanisms underlying this association and the potential
      implications for using volume as a criterion in plan choice.

PMID- 15569902
TI  - HIV testing and receipt of test results among homeless persons with serious
      mental illness.
AB  - OBJECTIVE: The purpose of this study was to determine the rates and predictors of
      HIV testing and receipt of results among homeless adults with serious mental
      illness in the initial 3-month period after contact with a community-based case
      management program. METHOD: Baseline and follow-up interview data came from
      clients (N=5,890) in the Access to Community Care and Effective Services and
      Supports program, an 18-site, 5-year federally sponsored demonstration designed
      to evaluate the effect of service system integration on outcomes for homeless
      persons with serious mental illness. RESULTS: Overall, 38.0% of clients were
      tested for HIV in the 3 months after program entry; of these, 88.8% returned to
      receive their test results. Likelihood of being tested was independently
      associated with having been tested before, more severe psychiatric symptoms and
      drug problems, level of worry about getting AIDS, younger age, less education,
      minority status, longer-term homelessness, being sexually assaulted, being
      arrested, and health services utilization. Among those tested, likelihood of
      receiving the test results was higher among those with a history of prior testing
      and return for results, a higher frequency of testing, and more years of
      education and lower among those with drug abuse problems, outpatient medical
      service utilization, disability, and sexually transmitted disease. Interaction
      analyses showed that, for men, greater social support increased the likelihood of
      both HIV testing and receipt of results, while sexual victimization during follow
      up decreased the likelihood that men would return for their HIV results.
      CONCLUSIONS: The majority of homeless clients enrolled in an intensive case
      management program were not tested for HIV during the 3-month period after
      program entry. Among those tested, however, nearly 90% reported receiving their
      results. The findings may enhance the development and targeting of strategies to
      increase testing and awareness of HIV serostatus among high-risk mentally ill
      homeless persons.

PMID- 15569903
TI  - Suicide rates among physicians: a quantitative and gender assessment (meta
      analysis).
AB  - OBJECTIVE: Physicians' suicide rates have repeatedly been reported to be higher
      than those of the general population or other academics, but uncertainty remains.
      In this study, physicians' suicide rate ratios were estimated with a meta
      analysis and systematic quality assessment of recent studies. METHOD: Studies of
      physicians' suicide rates were located in MEDLINE, PsycINFO, AARP Ageline, and
      the EBM Reviews: Cochrane Database of Systematic Reviews with the terms
      "physicians," "doctors," "suicide," and "mortality." Studies were included if
      they were published in or after 1960 and gave estimates of age-standardized
      suicide rates of physicians and their reference population or reported
      extractable data on physicians' suicide; 25 studies met the criteria. Reviewers
      extracted data and scored each study for quality. The studies were tested for
      heterogeneity and publication bias and were stratified by publication year,
      follow-up, and study quality. Effect sizes were pooled by using fixed-effects
      (women) and random-effects (men) models. RESULTS: The aggregate suicide rate
      ratio for male physicians, compared to the general population, was 1.41, with a
      95% confidence interval (CI) of 1.21-1.65. For female physicians the ratio was
      2.27 (95% CI=1.90-2.73). Visual inspection of funnel plots from tests of
      publication bias revealed randomness for men but some indication of bias for
      women, with a relative, nonsignificant lack of studies in the lower right
      quadrant. CONCLUSIONS: Studies on physicians' suicide collectively show modestly
      (men) to highly (women) elevated suicide rate ratios. Larger studies should help
      clarify whether female physicians' suicide rate is truly elevated or can be
      explained by publication bias.

PMID- 15569904
TI  - Religious affiliation and suicide attempt.
AB  - OBJECTIVE: Few studies have investigated the association between religion and
      suicide either in terms of Durkheim's social integration hypothesis or the
      hypothesis of the regulative benefits of religion. The relationship between
      religion and suicide attempts has received even less attention. METHOD: Depressed
      inpatients (N=371) who reported belonging to one specific religion or described
      themselves as having no religious affiliation were compared in terms of their
      demographic and clinical characteristics. RESULTS: Religiously unaffiliated
      subjects had significantly more lifetime suicide attempts and more first-degree
      relatives who committed suicide than subjects who endorsed a religious
      affiliation. Unaffiliated subjects were younger, less often married, less often
      had children, and had less contact with family members. Furthermore, subjects
      with no religious affiliation perceived fewer reasons for living, particularly
      fewer moral objections to suicide. In terms of clinical characteristics,
      religiously unaffiliated subjects had more lifetime impulsivity, aggression, and
      past substance use disorder. No differences in the level of subjective and
      objective depression, hopelessness, or stressful life events were found.
      CONCLUSIONS: Religious affiliation is associated with less suicidal behavior in
      depressed inpatients. After other factors were controlled, it was found that
      greater moral objections to suicide and lower aggression level in religiously
      affiliated subjects may function as protective factors against suicide attempts.
      Further study about the influence of religious affiliation on aggressive behavior
      and how moral objections can reduce the probability of acting on suicidal
      thoughts may offer new therapeutic strategies in suicide prevention.

PMID- 15569905
TI  - Influence of ethical safeguards on research participation: comparison of
      perspectives of people with schizophrenia and psychiatrists.
AB  - OBJECTIVE: Several safeguards have been developed to protect research volunteers,
      but little is known about how the people involved in this research-the
      stakeholders-view these efforts to assure participant rights and well-being. The
      authors' goal was to examine these perspectives. METHOD: As part of a larger
      study, 60 people with schizophrenia and 69 psychiatrists rated the protectiveness
      and influence on patients' willingness to participate in research of five
      safeguards: informed consent, alternative decision makers, institutional review
      boards, data safety monitoring boards, and confidentiality measures. RESULTS: All
      safeguards were perceived by both the participants with schizophrenia and by the
      psychiatrists as protective: on a scale of 1-5 on which 1=not protective at all
      and 5=very much protects, the mean scores ranged from 3.54 to 4.07. Four of the
      five safeguards were perceived by both the people with schizophrenia and by the
      psychiatrists as positively influencing patients' participation decisions. On a
      scale of 1-5 on which 1=much less willing and 5=much more willing to participate,
      the mean scores for these four safeguards ranged from 3.86 to 4.30. The mean
      score for the safeguard of an alternative decision maker, however, was 3.09. The
      ratings of protectiveness made by both the people with schizophrenia and the
      psychiatrists were correlated with their ratings of patients' willingness to
      participate in studies. CONCLUSIONS: Ethical commitment to research volunteers is
      expressed in safeguards. These efforts appear to be viewed positively by key
      stakeholders and may influence research participation decision making.

PMID- 15569906
TI  - Confirmation of synergy between urbanicity and familial liability in the
      causation of psychosis.
AB  - OBJECTIVE: This study replicated a previous report that there may be substantial
      synergism between urbanicity (a proxy environmental risk factor) and familial
      clustering of psychotic disorder (a proxy genetic risk factor). METHOD: The
      amount of synergism was estimated from the additive statistical interaction
      between urbanicity of place of birth and family history of schizophrenia or
      family history of any severe mental disorder in a population-based Danish cohort
      of 1,020,063 individuals. RESULTS: There was significant interaction between
      urbanicity and family history; between 20% and 35% of individuals who had been
      exposed to both of these risk factors had schizophrenia possibly because of their
      synergistic effects. CONCLUSIONS: The results suggest that a substantial
      proportion of the population morbidity force of schizophrenia may be the result
      of gene-environment interactions associated with urbanicity.

PMID- 15569907
TI  - Smaller nasal volumes as stigmata of aberrant neurodevelopment in schizophrenia.
AB  - OBJECTIVE: Anatomical and functional deficits of the olfactory neural system have
      been identified in patients with schizophrenia. Since olfactory structures
      develop in conjunction with both the palate and ventral forebrain, the authors
      hypothesized that schizophrenia patients might have structural abnormalities of
      the nasal cavity, which could represent specific markers of embryological
      dysmorphogenesis underlying schizophrenia. METHOD: A measurement of nasal volume
      was acquired by acoustic rhinometry for 40 male schizophrenia patients and 24
      healthy male comparison subjects. RESULTS: The patients had smaller posterior
      nasal volumes than the comparison subjects but did not differ in anterior nasal
      volumes. This difference persisted after covarying for height and smoking
      history. CONCLUSIONS: The lower observed posterior nasal volume likely reflects a
      specific developmental craniofacial abnormality. This finding confirms an early
      disruption in embryological development in males with schizophrenia and may
      represent a genetic or environmental "first hit" that leaves the individual
      vulnerable to subsequent pathology.

PMID- 15569908
TI  - Prevalence of chronic obstructive pulmonary disease among those with serious
      mental illness.
AB  - OBJECTIVE: Individuals with serious mental illness have elevated smoking rates,
      and smoking is a significant risk factor for chronic obstructive pulmonary
      disease (COPD). The goal was to determine the prevalence of COPD among those with
      serious mental illness. METHOD: The authors surveyed a random sample of 200
      adults with serious mental illness with questions from the National Health and
      Nutrition Examination Study III that were previously used to estimate the
      national prevalence of COPD. They compared the prevalence of COPD in the sample
      to a randomly selected matched subset of national comparison subjects. RESULTS:
      The prevalence of COPD was 22.6%. Those with serious mental illness were
      significantly more likely to have chronic bronchitis (19.5% versus 6.1%) and
      emphysema (7.9% versus 1.5%) than the comparison subjects. CONCLUSIONS: The
      prevalence of COPD is significantly higher among those with serious mental
      illness than comparison subjects. Improved primary and secondary prevention is
      warranted.

PMID- 15569909
TI  - Catechol O-methyltransferase polymorphism and eye tracking in schizophrenia: a
      preliminary report.
AB  - OBJECTIVE: This study examined associations between functional polymorphism
      (Val(108/158) Met) in the catechol O-methyltransferase (COMT) gene and eye
      tracking measures in schizophrenia. METHOD: Predictive pursuit and closed-loop
      gains of 62 patients with schizophrenia and 53 healthy comparison subjects with
      Val-Val, Val-Met, and Met-Met genotypes were compared. RESULTS: There was a
      significant diagnosis-by-genotype interaction: patients with the Met-Met genotype
      showed poor predictive pursuit. The Met-Met genotype in healthy subjects was
      associated with significantly higher predictive pursuit gain values than the Val
      Val genotype in healthy subjects. The COMT genotype explained about 10% of the
      variance in each group's predictive pursuit performance. DISCUSSION: These
      preliminary data suggest that the COMT gene is associated with predictive eye
      tracking performance in healthy subjects. Predictive pursuit abnormality in
      schizophrenia is not attributable to the Val allele. These findings suggest a
      complex interaction with other etiological factors (e.g., another gene), and/or
      with prefrontal cortical dopaminergic activity.

PMID- 15569910
TI  - Prediction of outcome in bulimia nervosa by early change in treatment.
AB  - OBJECTIVE: The authors' goal was to identify predictors of treatment response in
      bulimia nervosa and, in particular, to attempt to replicate and extend the
      observation that early change predicts outcome. METHOD: Predictors of response at
      the end of treatment and 8-month follow-up were sought from a group of 220 women
      treated with either cognitive behavior therapy or interpersonal psychotherapy.
      RESULTS: Early change in frequency of purging was the best predictor of response
      at the end of treatment and at 8-month follow-up. CONCLUSIONS: Early change in
      treatment is a robust and potent predictor of immediate and longer-term outcome
      in bulimia nervosa.

PMID- 15569911
TI  - Bradycardia at low doses of risperidone.

PMID- 15569912
TI  - Mirtazapine and breast-feeding.

PMID- 15569913
TI  - Withdrawal syndrome after delayed tramadol intake.

PMID- 15569914
TI  - Catatonia in psychiatric classification.

PMID- 15569915
TI  - Publication bias against eating disorders?

PMID- 15569916
TI  - Family therapy and a physician's suicide.

PMID- 15569917
TI  - Family therapy and a physician's suicide.

PMID- 15569918
TI  - Family therapy and a physician's suicide.

PMID- 15569919
TI  - Interferon for hepatitis C patients with psychiatric disorders.

PMID- 15569920
TI  - Interferon for hepatitis C patients with psychiatric disorders.

PMID- 15569921
TI  - Interferon for hepatitis C patients with psychiatric disorders.

PMID- 15569922
TI  - Single-cell FRET imaging of phosphatase activity in the Escherichia coli
      chemotaxis system.
AB  - Two-component signaling systems, in which a receptor-coupled kinase is used to
      control the phosphorylation level of a response regulator, are commonly used in
      bacteria to sense their environment. In the chemotaxis system of Escherichia
      coli, the receptors, and thus the kinase, are clustered on the inner cell
      membrane. The phosphatase of this system also is recruited to receptor clusters,
      but the reason for this association is not clear. By using FRET imaging of single
      cells, we show that in vivo the phosphatase activity is substantially larger at
      the cluster, indicating that the signaling source (the kinase) and the signaling
      sink (the phosphatase) tend to be located at the same place in the cell. When
      this association is disrupted, a gradient in the concentration of the
      phosphorylated response regulator appears, and the chemotactic response is
      degraded. Such colocalization is inevitable in systems in which the activity of
      the kinase and the phosphatase are produced by the same enzyme. Evidently, this
      design enables a more rapid and spatially uniform response.

PMID- 15569923
TI  - EST-based genome-wide gene inactivation identifies ARAP3 as a host protein
      affecting cellular susceptibility to anthrax toxin.
AB  - The lethality of infection by Bacillus anthracis is largely due to its plasmid
      encoded toxins, which consist of a carrier protein, the protective antigen (PA),
      in combination with either the lethal-factor or edema-factor moiety. During B.
      anthracis infections, PA secreted by bacteria binds to membrane receptors of
      susceptible cells, is cleaved proteolytically, attaches to lethal factor or edema
      factor, undergoes oligomerization and internalization, and transports its toxin
      partners to acidic endosomes where they are released into the cytosol. To
      identify specific host functions that mediate these events, we used RNA encoded
      by a lentivirus-based library of approximately 40,000 human ESTs to inactivate
      chromosomal genes in a human cell population, and we isolated clones that
      survived PA-dependent toxin-induced death. This phenotypic screen and subsequent
      analysis identified ARAP3, which is a phosphoinositide-binding protein implicated
      previously in membrane vesicle trafficking and cytoskeletal organization, as a
      mammalian host-cell gene that is essential for normal anthrax toxicity. ARAP3
      deficiency produced by antisense expression of an ARAP3 EST impaired entry of PA
      and its bound toxigenic moieties into both human and mouse cells, resulting in
      reduced toxin sensitivity. Our results demonstrate the usefulness of antisense
      EST libraries for global chromosomal gene inactivation, establish the
      practicality of loss-of-function phenotypic screens for the identification of
      genomic loci required for pathogen effects in mammalian cells, and reveal an
      important role for ARAP3 in cellular internalization of anthrax toxin.

PMID- 15569924
TI  - Use of coherent control methods through scattering biological tissue to achieve
      functional imaging.
AB  - We test whether coherent control methods based on ultrashort-pulse phase shaping
      can be applied when the laser light propagates through biological tissue. Our
      results demonstrate experimentally that the spectral-phase properties of shaped
      laser pulses optimized to achieve selective two-photon excitation survive as the
      laser pulses propagate through tissue. This observation is used to obtain
      functional images based on selective two-photon excitation of a pH-sensitive
      chromophore in a sample that is placed behind a slice of biological tissue. Our
      observation of coherent control through scattering tissue suggests possibilities
      in multiphoton-based imaging and photodynamic therapy.

PMID- 15569925
TI  - Functional regulatory immune responses against human cartilage glycoprotein-39 in
      health vs. proinflammatory responses in rheumatoid arthritis.
AB  - The class of immune response against autoantigens could profoundly influence the
      onset and/or outcome of autoimmune diseases. Until now, there is only limited
      information on the antigen-specific balance between proinflammatory and
      regulatory responses in humans. Here we analyzed the natural immune response
      against a candidate autoantigen in rheumatoid arthritis, human cartilage
      glycoprotein-39 (HC gp-39). Peripheral blood mononuclear cells from healthy
      individuals reacted against HC gp-39 with the production of IL-10 but not IFN
      gamma. Ex vivo assays indicated that the naturally occurring HC gp-39-specific
      immune response in bulk is powerful enough to suppress antigen-specific recall
      responses, demonstrating that rather than being unresponsive, the HC gp-39
      directed immune response in healthy individuals shows a strong bias toward a
      regulatory phenotype. Moreover, CD4(+) T cell lines directed against HC gp-39
      expressed CD25, glucocorticoid-induced tumor necrosis factor receptor, and Foxp3
      molecules and were capable of suppressing antigen-specific T cell responses. Cell
      cell contact was required for this suppression. As opposed to healthy
      individuals, the HC gp-39-directed immune response in 50% of patients with
      rheumatoid arthritis exhibits polarization toward a proinflammatory T helper 1
      phenotype and is significantly less powerful in suppressing antigen-specific
      recall responses. Together these findings indicate that the presence of HC gp-39
      specific immune responses in healthy individuals may have an inhibitory effect on
      inflammatory responses in areas where HC gp-39 is present. Furthermore, these
      data indicate that the class of HC gp-39-directed immune response in rheumatoid
      arthritis patients has shifted from an antiinflammatory toward a proinflammatory
      phenotype.

PMID- 15569926
TI  - A critical role for p27kip1 gene dosage in a mouse model of prostate
      carcinogenesis.
AB  - In human prostate cancer, the frequent down-regulation of p27(kip1) protein
      expression is correlated with poor clinical outcome, yet p27(kip1) rarely
      undergoes mutational inactivation. Here, we investigate the consequences of
      reducing or eliminating p27(kip1) function for prostate carcinogenesis in the
      context of a mouse modeling lacking the Nkx3.1 homeobox gene and the Pten tumor
      suppressor. Unexpectedly, we find that triple mutant mice heterozygous for a
      p27(kip1) null allele (Nkx3.1(+/- or -/-); Pten(+/-); p27(+/-)) display enhanced
      prostate carcinogenesis, whereas mice that are homozygous null for p27(kip1)
      (Nkx3.1(+/- or -/-); Pten(+/-); p27(-/-)) show inhibition of cancer progression.
      Expression profiling reveals that Cyclin D1 is highly up-regulated in compound
      p27(kip1) heterozygotes, but is down-regulated in the compound p27(kip1)
      homozygous mutants. Using RNA interference in prostate cancer cell lines with
      distinct p27(kip1) gene doses, we show that prostate tumorigenicity depends on
      levels of p27(kip1) and that the consequences of p27(kip1) gene dosage can be
      attributed, in part, to altered levels of Cyclin D1. Our findings suggest that
      p27(kip1) possesses dosage-sensitive positive as well as negative modulatory
      roles in prostate cancer progression.

PMID- 15569927
TI  - Tyrosine phosphorylation sites on FRS2alpha responsible for Shp2 recruitment are
      critical for induction of lens and retina.
AB  - Early development of the lens and retina depends upon reciprocal inductive
      interactions between the embryonic surface ectoderm and the underlying
      neuroepithelium of the optic vesicle. FGF signaling has been implicated in this
      signal exchange. The docking protein FRS2alpha is a major mediator of FGF
      signaling by providing a link between FGF receptors (FGFRs) and a variety of
      intracellular signaling pathways. After FGF stimulation, tyrosine-phosphorylated
      FRS2alpha recruits four molecules of the adaptor protein Grb2 and two molecules
      of the protein tyrosine phosphatase Shp2, resulting in activation of the
      Ras/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3
      kinase/Akt signaling pathways. In this report, we explore the role of signaling
      pathways downstream of FRS2alpha in eye development by analyzing the phenotypes
      of mice that carry point mutations in either the Grb2-(Frs2alpha(4F)) or the Shp2
      binding sites (Frs2alpha(2F)) of FRS2alpha. Although Frs2alpha(4F/4F) mice
      exhibited normal early eye development, all Frs2alpha(2F/2F) embryos were
      defective in eye development and showed anophthalmia or microphthalmia.
      Consistent with the critical role of FRS2alpha in FGF signaling, the level of
      activated extracellular signal-regulated kinase in Frs2alpha(2F/2F) embryos was
      significantly lower than that observed in wild-type embryos. Furthermore,
      expression of Pax6 and Six3, molecular markers for lens induction, were decreased
      in the Frs2alpha(2F/2F) presumptive lens ectoderm. Similarly, the expression of
      Chx10 and Bmp4, genes required for retinal precursor proliferation and for lens
      development, respectively, was also decreased in the optic vesicles of
      Frs2alpha(2F/2F) mice. These experiments demonstrate that intracellular signals
      that depend on specific tyrosine residues in FRS2alpha lie upstream of gene
      products critical for induction of lens and retina.

PMID- 15569928
TI  - Phospholipid bilayer surface configuration probed quantitatively by (31)P field
      cycling NMR.
AB  - (31)P relaxation of the diester phosphate of phospholipids in unilamellar
      vesicles has been studied from 0.004 to 11.7 T. Relaxation at very low fields,
      below 0.1 T, shows a rate increase that reflects a residual dipolar interaction
      with neighboring protons, probably dominated by the glycerol C3 protons. This
      interaction is not fully averaged by faster motion such as rotational diffusion
      perpendicular to the membrane surface. The remaining dipolar interaction,
      modulated by overall rotational diffusion of the vesicle and lateral diffusion of
      the lipid molecules, is responsible for the very low-field relaxation. These
      measurements yield a good estimate of the time-average angle between the membrane
      surface and the vector connecting the phosphorus to the glycerol C3 protons,
      based on the classic theory by Woessner. Dynamic information is also obtained.
      Implications for solid-state NMR and other studies are discussed.

PMID- 15569929
TI  - Striatin assembles a membrane signaling complex necessary for rapid, nongenomic
      activation of endothelial NO synthase by estrogen receptor alpha.
AB  - Steroid hormone receptors (SHRs) are ligand-activated transcription factors that
      regulate gene expression. SHRs also mediate rapid, nongenomic cellular activation
      by steroids. In vascular endothelial cells, the SHR for estrogen, estrogen
      receptor (ER) alpha, is targeted by unknown mechanisms to a functional signaling
      module in membrane caveolae that enables estrogen to rapidly activate the mitogen
      activated protein kinase and phosphatidylinositol 3-Akt kinase pathways, and
      endothelial NO synthase (eNOS). Here we identify the 110-kDa caveolin-binding
      protein striatin as the molecular anchor that localizes ERalpha to the membrane
      and organizes the ERalpha-eNOS membrane signaling complex. Striatin directly
      binds to amino acids 183-253 of ERalpha, targets ERalpha to the cell membrane,
      and serves as a scaffold for the formation of an ERalpha-Galphai complex.
      Disruption of complex formation between ERalpha and striatin blocks estrogen
      induced rapid activation mitogen-activated protein kinase, Akt kinase, and eNOS,
      but has no effect on ER-dependent regulation of an estrogen response element
      driven reporter plasmid. These findings identify striatin as a molecular scaffold
      required for rapid, nongenomic estrogen-mediated activation of downstream
      signaling pathways. Furthermore, by demonstrating independent regulation of
      nongenomic vs. genomic ER-dependent signaling, these findings provide conceptual
      support for the potential development of "pathway-specific" selective ER
      modulators.

PMID- 15569930
TI  - 7alpha-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor
      activity of breeding newts by means of the dopaminergic system.
AB  - It is becoming clear that steroids can be synthesized de novo by the brain and
      other nervous systems. Such steroids are called neurosteroids, and de novo
      neurosteroidogenesis from cholesterol is a conserved property of vertebrate
      brains. In this study, we show that the newt brain actively produces 7alpha
      hydroxypregnenolone, a previously undescribed amphibian neurosteroid that
      stimulates locomotor activity. 7alpha-hydroxypregnenolone was identified as a
      most abundant amphibian neurosteroid in the newt brain by using biochemical
      techniques combined with HPLC, TLC, and GC-MS analyses. The production of 7alpha
      hydroxypregnenolone in the diencephalon and rhombencephalon was higher than that
      in the telencephalon and peripheral steroidogenic glands. In addition, 7alpha
      hydroxypregnenolone synthesis in the brain showed marked changes during the
      annual breeding cycle, with a maximal level in the spring breeding period when
      locomotor activity of the newt increases. Behavioral analysis of newts in the
      nonbreeding period demonstrated that administration of this previously
      undescribed amphibian neurosteroid acutely increased locomotor activity. In vitro
      analysis further revealed that 7alpha-hydroxypregnenolone treatment resulted in a
      dose-dependent increase in the release of dopamine from cultured brain tissue of
      nonbreeding newts. The effect of this neurosteroid on locomotion also was
      abolished by dopamine D(2)-like receptor antagonists. These results indicate that
      7alpha-hydroxypregnenolone acts as a neuronal activator to stimulate locomotor
      activity of breeding newts through the dopaminergic system. This study
      demonstrates a physiological function of 7alpha-hydroxypregnenolone that has not
      been described previously in any vertebrate class. This study also provides
      findings on the regulatory mechanism of locomotor activity from a unique
      standpoint.

PMID- 15569931
TI  - ErbB2 is required for ductal morphogenesis of the mammary gland.
AB  - The ERBB2/HER2/NEU receptor tyrosine kinase gene is amplified in up to 30% of
      human breast cancers. The frequent and specific selection of this receptor kinase
      gene for amplification in breast cancer implies that it has important normal
      functions in the mammary gland. To investigate the functions of ErbB2 during
      normal mouse mammary gland development, we transplanted mammary buds from
      genetically rescued ErbB2(-/-) embryos that express ErbB2 in the cardiac muscle.
      ErbB2(-/-) mammary buds transplanted to a wild-type mammary fat pad support
      outgrowth of an epithelial tree that advances only slowly through the mammary fat
      pad at puberty. This penetration defect is associated with structural defects in
      terminal end buds, characterized by a decrease in body cell number, an increased
      presence of cap-like cells in the prelumenal compartment, and the presence of
      large luminal spaces. Lobuloalveolar development was not affected in glands that
      developed from ErbB2(-/-) transplanted tissue. The results may have implications
      for the aggressive phenotypes associated with ERBB2-overexpressing mammary
      carcinomas.

PMID- 15569932
TI  - Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces
      leukemia development.
AB  - Normal blood-cell differentiation is controlled by regulated gene expression and
      signal transduction. Transcription deregulation due to chromosomal translocation
      is a common theme in hematopoietic neoplasms. AML1-ETO, which is a fusion protein
      generated by the 8;21 translocation that is commonly associated with the
      development of acute myeloid leukemia, fuses the AML1 runx family DNA-binding
      transcription factor to the ETO corepressor that associates with histone
      deacetylase complexes. Analyses have demonstrated that AML1-ETO blocks AML1
      function and requires additional mutagenic events to promote leukemia. Here, we
      report that the loss of the molecular events of AML1-ETO C-terminal NCoR/SMRT
      interacting domain transforms AML1-ETO into a potent leukemogenic protein.
      Contrary to full-length AML1-ETO, the truncated form promotes in vitro growth and
      does not obstruct the cell-cycle machinery. These observations suggest a
      previously uncharacterized mechanism of tumorigenesis, in which secondary
      mutation(s) in molecular events disrupting the function of a domain of the
      oncogene promote the development of malignancy.

PMID- 15569933
TI  - Cooperative extraction of membrane nanotubes by molecular motors.
AB  - In eukaryotic cells, nanotubes represent a substantial fraction of transport
      intermediates between organelles. They are extracted from membranes by molecular
      motors walking along microtubules. We previously showed that kinesins fixed on
      giant unilamellar vesicles in contact with microtubules are sufficient to form
      nanotubes in vitro. Motors were attached to the membrane through beads, thus
      facilitating cooperative effects. Koster et al. proposed that motors could
      dynamically cluster at the tip of tubes when they are individually attached to
      the membrane. We demonstrate, in a recently designed experimental system, the
      existence of an accumulation of motors allowing tube extraction. We determine the
      motor density along a tube by using fluorescence intensity measurements. We also
      perform a theoretical analysis describing the dynamics of motors and tube growth.
      The only adjustable parameter is the motor binding rate onto microtubules, which
      we measure to be 4.7 +/- 2.4 s(-1). In addition, we quantitatively determine, for
      a given membrane tension, the existence of a threshold in motor density on the
      vesicle above which nanotubes can be formed. We find that the number of motors
      pulling a tube can range from four at threshold to a few tens away from it. The
      threshold in motor density (or in membrane tension at constant motor density)
      could be important for the understanding of membrane traffic regulation in cells.

PMID- 15569934
TI  - Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor
      aggressiveness and potential therapeutic target.
AB  - Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally
      restricted to macrophage-lineage cells, providing a potential costimulatory
      signal source for regulation of T cell activation. In contrast, aberrant
      expression of B7-H1 by tumor cells has been implicated in impairment of T cell
      function and survival, resulting in defective host antitumoral immunity. The
      relationship between tumor-associated B7-H1 and clinical cancer progression is
      unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC)
      tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our
      analysis of 196 clinical specimens reveals that patients harboring high
      intratumoral expression levels of B7-H1, contributed by tumor cells alone,
      lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive
      tumors and are at markedly increased risk of death from RCC. In fact, patients
      with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die
      from their cancer than patients exhibiting low levels of B7-H1 expression (risk
      ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study
      suggests a previously undescribed mechanism whereby RCC may impair host immunity
      to foster tumor progression. B7-H1 may prove useful as a prognostic variable for
      RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a
      promising target to facilitate more favorable responses in patients who require
      immunotherapy for treatment of advanced RCC.

PMID- 15569935
TI  - Neurochemical and behavioral consequences of widespread gene knockdown in the
      adult mouse brain by using nonviral RNA interference.
AB  - Gene expression analysis implicates an increasing number of novel genes in the
      brain as potential targets for the treatment of neurological and psychiatric
      disorders. Frequently, these genes are ubiquitously expressed in the brain and,
      thus, may contribute to a pathophysiological state through actions in several
      brain nuclei. Current strategies employing genetically modified animals for in
      vivo validation of such targets are time-consuming and often limited by
      developmental adaptations. Somatic gene manipulation using viral-mediated RNA
      interference (RNAi) has emerged recently, although restricting the target
      validation to specific brain nuclei. We investigated whether nonviral infusion of
      short interfering RNA (siRNA) into the ventricular system would enable a sequence
      specific gene knockdown. The temporality and extent of siRNA-induced down
      regulation were analyzed by targeting a transgene, EGFP, in mice overexpressing
      EGFP. Extensive knockdown of EGFP was observed, especially in regions adjacent or
      dorsoventrally and mediolaterally distant to the infusion site (dorsal third
      ventricle), with lesser knockdown in more distal regions. We challenged our RNAi
      approach to generate a specific knockdown of an endogenous gene, encoding the
      dopamine transporter (DAT) in regions (ventral midbrain) far distal to the
      infusion site. DAT-siRNA infusion in adult mice produced a significant down
      regulation of DAT mRNA and protein in the brain and also elicited a temporal
      hyperlocomotor response similar to that (but delayed) obtained upon infusion of
      GBR-12909, a pharmacologically selective DAT inhibitor. Application of this
      nonviral RNAi approach may accelerate target validation for neuropsychiatric
      disorders that involve a complex interplay of gene(s) from various brain regions.

PMID- 15569936
TI  - Structural basis of activity and allosteric control of diguanylate cyclase.
AB  - Recent discoveries suggest that a novel second messenger, bis-(3'-->5')-cyclic di
      GMP (c-diGMP), is extensively used by bacteria to control multicellular behavior.
      Condensation of two GTP to the dinucleotide is catalyzed by the widely
      distributed diguanylate cyclase (DGC or GGDEF) domain that occurs in various
      combinations with sensory and/or regulatory modules. The crystal structure of the
      unorthodox response regulator PleD from Caulobacter crescentus, which consists of
      two CheY-like receiver domains and a DGC domain, has been solved in complex with
      the product c-diGMP. PleD forms a dimer with the CheY-like domains (the stem)
      mediating weak monomer-monomer interactions. The fold of the DGC domain is
      similar to adenylate cyclase, but the nucleotide-binding mode is substantially
      different. The guanine base is H-bonded to Asn-335 and Asp-344, whereas the
      ribosyl and alpha-phosphate moieties extend over the beta2-beta3-hairpin that
      carries the GGEEF signature motif. In the crystal, c-diGMP molecules are
      crosslinking active sites of adjacent dimers. It is inferred that, in solution,
      the two DGC domains of a dimer align in a two-fold symmetric way to catalyze c
      diGMP synthesis. Two mutually intercalated c-diGMP molecules are found tightly
      bound at the stem-DGC interface. This allosteric site explains the observed
      noncompetitive product inhibition. We propose that product inhibition is due to
      domain immobilization and sets an upper limit for the concentration of this
      second messenger in the cell.

PMID- 15569937
TI  - Restricted inactivation of serum response factor to the cardiovascular system.
AB  - Serum response factor (SRF) directs programs of gene expression linked to growth
      and muscle differentiation. To investigate the role of SRF in cardiovascular
      development, we generated mice in which SRF is knocked out in >80% of
      cardiomyocytes and >50% of vascular smooth muscle cells (SMC) through SM22alpha
      Cre-mediated excision of SRF's promoter and first exon. Mutant mice display
      vascular patterning, cardiac looping, and SRF-dependent gene expression through
      embryonic day (e)9.5. At e10.5, attenuation in cardiac trabeculation and compact
      layer expansion is noted, with an attendant decrease in vascular SMC recruitment
      to the dorsal aorta. Ultrastructurally, cardiac sarcomeres and Z disks are highly
      disorganized in mutant embryos. Moreover, SRF mutant mice exhibit vascular SMC
      lacking organizing actin/intermediate filament bundles. These structural defects
      in the heart and vasculature coincide with decreases in SRF-dependent gene
      expression, such that by e11.5, when mutant embryos succumb to death, no SRF
      dependent mRNA expression is evident. These results suggest a vital role for SRF
      in contractile/cytoskeletal architecture necessary for the proper assembly and
      function of cardiomyocytes and vascular SMC.

PMID- 15569939
TI  - slo K(+) channel gene regulation mediates rapid drug tolerance.
AB  - Changes in neural activity caused by exposure to drugs may trigger homeostatic
      mechanisms that attempt to restore normal neural excitability. In Drosophila, a
      single sedation with the anesthetic benzyl alcohol changes the expression of the
      slo K(+) channel gene and induces rapid drug tolerance. We demonstrate linkage
      between these two phenomena by using a mutation and a transgene. A mutation that
      eliminates slo expression prevents tolerance, whereas expression from an
      inducible slo transgene mimics tolerance in naive animals. The behavioral
      response to benzyl alcohol can be separated into an initial phase of hyperkinesis
      and a subsequent phase of sedation. The hyperkinetic phase causes a drop in slo
      gene expression and makes animals more sensitive to benzyl alcohol. It is the
      sedative phase that stimulates slo gene expression and induces tolerance. We
      demonstrate that the expression level of slo is a predictor of drug sensitivity.

PMID- 15569938
TI  - Phenotypic differences between Salmonella and Escherichia coli resulting from the
      disparate regulation of homologous genes.
AB  - Phenotypic differences among closely related bacteria have been largely ascribed
      to species-specific genes, such as those residing in pathogenicity islands.
      However, we now report that the differential regulation of homologous genes is
      the mechanism responsible for the divergence of the enteric bacteria Salmonella
      enterica and Escherichia coli in their ability to make LPS modifications
      mediating resistance to the antibiotic polymyxin B. In S. enterica serovar
      Typhimurium, the PmrA/PmrB two-component system governing polymyxin B resistance
      is induced in low Mg(2+) in a process that requires the PmrD protein and by
      Fe(3+) in a PmrD-independent fashion. We establish that E. coli K-12 induces PmrA
      activated gene transcription and polymyxin B resistance in response to Fe(3+),
      but that it is blind to the low Mg(2+) signal. The highly divergent PmrD protein
      is responsible for this phenotype as replacement of the E. coli pmrD gene by its
      Salmonella counterpart resulted in an E. coli strain that transcribed PmrA
      activated genes and displayed polymyxin B resistance under the same conditions as
      Salmonella. Molecular analysis of natural isolates of E. coli and Salmonella
      revealed that the PmrD proteins are conserved within each genus and that
      selection might have driven the divergence between the Salmonella and E. coli
      PmrD proteins. Investigation of PmrD function demonstrated statistically
      different distributions for the Salmonella and E. coli isolates in PmrD-dependent
      transcription occurring in low Mg(2+). Our results suggest that the differential
      regulation of conserved genes may have ecological consequences, determining the
      range of niches a microorganism can occupy.

PMID- 15569940
TI  - Identification and modulation of a caveolae-dependent signal pathway that
      regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes.
AB  - Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the
      pathogenesis of obesity-driven type 2 diabetes mellitus and associated
      cardiovascular complications. Here, we show that perturbation of caveolar
      microdomains leads to insulin resistance and concomitant up-regulation of PAI-1
      in 3T3L1 adipocytes. We present several lines of evidence showing that the
      phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene
      expression. Insulin-induced PAI-1 gene expression is up-regulated by a specific
      inhibitor of PI3K. In addition, serum PAI-1 level is elevated in protein kinase
      Balpha-deficient mice, whereas it is reduced in p70 ribosomal S6 kinase 1
      deficient mice. The PI3K pathway phosphorylates retinoblastoma protein (pRB),
      known to release free E2 (adenoviral protein) factor (E2F), which we have
      previously demonstrated to be a transcriptional repressor of PAI-1 gene
      expression. Accordingly, cell-penetrating peptides that disrupt pRB-E2F
      interaction, and thereby release free E2F, are able to suppress PAI-1 levels that
      are elevated during insulin-resistant conditions. This study identifies a
      caveolar-dependent signal pathway that up-regulates PAI-1 in insulin-resistant
      adipocytes and proposes a previously undescribed pharmacological paradigm of
      disrupting pRB-E2F interaction to suppress PAI-1 levels.

PMID- 15569941
TI  - Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism,
      defects in gonadal steroidogenesis, and infertility.
AB  - Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) act on gonadal
      cells to promote steroidogenesis and gametogenesis. Clarifying the in vivo roles
      of LH and FSH permits a feasible approach to contraception involving selective
      blockade of gonadotropin action. One way to address these physiologically
      important problems is to generate mice with an isolated LH deficiency and compare
      them with existing FSH loss-of-function mice. To model human reproductive
      disorders involving loss of LH function and to define LH-responsive genes, we
      produced knockout mice lacking the hormone-specific LHbeta-subunit. LHbeta-null
      mice are viable but demonstrate postnatal defects in gonadal growth and function
      resulting in infertility. Mutant males have decreased testes size, prominent
      Leydig cell hypoplasia, defects in expression of genes encoding steroid
      biosynthesis pathway enzymes, and reduced testosterone levels. Furthermore,
      spermatogenesis is blocked at the round spermatid stage, causing a total absence
      of the elongated spermatids. Mutant female mice are hypogonadal and demonstrate
      decreased levels of serum estradiol and progesterone. Ovarian histology
      demonstrates normal thecal layer, defects in folliculogenesis including many
      degenerating antral follicles, and absence of corpora lutea. The defects in both
      sexes are not secondary to aberrant FSH regulation, because FSH levels were
      unaffected in null mice. Finally, both male and female null mice can be
      pharmacologically rescued by exogenous human chorionic gonadotropin, indicating
      that LH-responsiveness of the target cells is not irreversibly lost. Thus, LHbeta
      null mice represent a model to study the consequences of an isolated deficiency
      of LH ligand in reproduction, while retaining normal LH-responsiveness in target
      cells.

PMID- 15569942
TI  - The VASP tetramerization domain is a right-handed coiled coil based on a 15
      residue repeat.
AB  - The vasodilator-stimulated phosphoprotein (VASP) is a key regulator of actin
      dynamics. We have determined the 1.3-A resolution crystal structure of the 45
      residue-long tetramerization domain (TD) from human VASP. This domain forms a
      right-handed alpha-helical coiled-coil structure with a similar degree of
      supercoiling as found in the widespread left-handed coiled coils with heptad
      repeats. The basis for the right-handed geometry of VASP TD is a 15-residue
      repeat in its amino acid sequence, which reveals a characteristic pattern of
      hydrophobic residues. Hydrophobic interactions and a network of salt bridges
      render VASP TD highly thermostable with a melting point of 120 degrees C.

PMID- 15569943
TI  - Adapting to an invasive species: toxic cane toads induce morphological change in
      Australian snakes.
AB  - The arrival of invasive species can devastate natural ecosystems, but the long
      term effects of invasion are less clear. If native organisms can adapt to the
      presence of the invader, the severity of impact will decline with time. In
      Australia, invasive cane toads (Bufo marinus) are highly toxic to most snakes
      that attempt to eat them. Because snakes are gape-limited predators with strong
      negative allometry for head size, maximum relative prey mass (and thus, the
      probability of eating a toad large enough to be fatal) decreases with an increase
      in snake body size. Thus, the arrival of toads should exert selection on snake
      morphology, favoring an increase in mean body size and a decrease in relative
      head size. We tested these predictions with data from specimens of four species
      of Australian snakes, collected over >80 years. Geographic information system
      layers provided data on the duration of toad exposure for each snake population,
      as well as environmental variables (latitude, precipitation, and temperature). As
      predicted, two toad-vulnerable species (Pseudechis porphyriacus and Dendrelaphis
      punctulatus) showed a steady reduction in gape size and a steady increase in body
      length with time since exposure to toads. In contrast, two species at low risk
      from toads (Hemiaspis signata and Tropidonophis mairii) showed no consistent
      change in these morphological traits as a function of the duration of toad
      exposure. These results provide strong evidence of adaptive changes in native
      predators as a result of the invasion of toxic prey.

PMID- 15569944
TI  - Agrobacterium VirB10, an ATP energy sensor required for type IV secretion.
AB  - Bacteria use type IV secretion systems (T4SS) to translocate DNA and protein
      substrates to target cells of phylogenetically diverse taxa. Recently, by use of
      an assay termed transfer DNA immunoprecipitation (TrIP), we described the
      translocation route for a DNA substrate [T-DNA, portion of the Ti (tumor
      inducing) plasmid that is transferred to plant cells] of the Agrobacterium
      tumefaciens VirB/D4 T4SS in terms of a series of temporally and spatially ordered
      substrate contacts with subunits of the secretion channel. Here, we report that
      the bitopic inner membrane protein VirB10 undergoes a structural transition in
      response to ATP utilization by the VirD4 and VirB11 ATP-binding subunits, as
      monitored by protease susceptibility. VirB10 interacts with inner membrane VirD4
      independently of cellular energetic status, whereas the energy-induced
      conformational change is required for VirB10 complex formation with an outer
      membrane-associated heterodimer of VirB7 lipoprotein and VirB9, as shown by
      coimmunoprecipitation. Under these conditions, the T-DNA substrate is delivered
      from the inner membrane channel components VirB6 and VirB8 to periplasmic and
      outer membrane-associated VirB2 pilin and VirB9. We propose that VirD4 and VirB11
      coordinate the ATP-dependent formation of a VirB10 "bridge" between inner and
      outer membrane subassemblies of the VirB/D4 T4SS, and that this morphogenetic
      event is required for T-DNA translocation across the A. tumefaciens cell
      envelope.

PMID- 15569945
TI  - Single-chip mechatronic microsystem for surface imaging and force response
      studies.
AB  - We report on a stand-alone single-chip (7 x 10 mm) atomic force microscopy unit
      including a fully integrated array of cantilevers, each of which has an
      individual actuation, detection, and control unit so that standard atomic force
      microscopy operations can be performed by means of the chip only without any
      external controller. The system offers drastically reduced overall size and costs
      as well as increased scanning speed and can be fabricated with standard
      complementary metal oxide semiconductor technology with some subsequent
      micromachining steps to form the cantilevers. Full integration of microelectronic
      and micromechanical components on the same chip allows for the controlling and
      monitoring of all system functions. The on-chip circuitry, which includes analog
      signal amplification and filtering stages with offset compensation, analog-to
      digital converters, a powerful digital signal processor, and an on-chip digital
      interface for data transmission, notably improves the overall system performance.
      The microsystem characterization evidenced a vertical resolution of < 1 nm and a
      force resolution of < 1 nN as shown in the measurement results. The monolithic
      system represents a paradigm of a mechatronic microsystem that allows for precise
      and fully controlled mechanical manipulation in the nanoworld.

PMID- 15569946
TI  - Evaluating education as an intervention for injury control.

PMID- 15569947
TI  - The standard of care debate: conceptual clarifications.

PMID- 15569948
TI  - Communication at the core of effective public health.

PMID- 15569949
TI  - The contributions of health communication to eliminating health disparities.

PMID- 15569950
TI  - Confronting health inequity: the global dimension.

PMID- 15569951
TI  - Asleep at the switch: local public health and chronic disease.

PMID- 15569952
TI  - The Latina paradox: an opportunity for restructuring prenatal care delivery.
AB  - Latina mothers in the United States enjoy surprisingly favorable birth outcomes
      despite their social disadvantages. This "Latina paradox" is particularly evident
      among Mexican-born women. The social and cultural factors that contribute to this
      paradox are maintained by community networks--informal systems of prenatal care
      that are composed of family, friends, community members, and lay health workers.
      This informal system confers protective factors that provide a behavioral context
      for healthy births. US-born Latinas are losing this protection, although it could
      be maintained with the support of community-based informal care systems. We
      recommend steps to harness the benefits of informal systems of prenatal care in
      Latino communities to meet the increasing needs of pregnant Latina women.

PMID- 15569953
TI  - Self-care among chronically ill African Americans: culture, health disparities,
      and health insurance status.
AB  - Little is known about the self-care practices of chronically ill African
      Americans or how lack of access to health care affects self-care. Results from a
      qualitative interview study of 167 African Americans who had one or more chronic
      illnesses found that self-care practices were culturally based, and the insured
      reported more extensive programs of self-care. Those who had some form of health
      insurance much more frequently reported the influence of physicians and health
      education programs in self-care regimens than did those who were uninsured. It is
      concluded that the cultural components of self-care have been underemphasized,
      and further, that the potential to maximize chronic illness management through
      self-care strategies is not realized for those who lack access to health care.

PMID- 15569954
TI  - Variations in health communication needs among combat veterans.
AB  - In this cross-sectional study of US military combat veterans, we assessed the
      helpfulness of different media for providing health risk communication messages.
      We have provided preliminary results from a postal survey of 5000 veterans
      sampled because of their deployment to Vietnam, the Persian Gulf, or Bosnia
      Kosovo. Respondents endorsed the primary care provider as the most helpful source
      of health information. Access to the Internet and use of this medium for seeking
      health information differed by race, age, and cohort.

PMID- 15569955
TI  - Accounting for apparent "reverse" racial disparities in Department of Veterans
      Affairs (VA)-based medical care: influence of out-of-VA care.
AB  - Conclusions regarding racial differences in care following a newly elevated
      prostate-specific antigen (PSA) test at the Department of Veterans Affairs (VA)
      may differ depending on whether follow-up care outside the VA is considered.
      Consecutive Philadelphia, Pa, VA patients with newly elevated PSA tests (n = 183)
      were interviewed 1 year after baseline. Among exclusive VA users, Blacks had
      higher rates of urology referrals and prostate biopsies compared with Whites.
      However, these racial differences were attenuated when care obtained outside the
      VA also was considered.

PMID- 15569956
TI  - The health impact of resolving racial disparities: an analysis of US mortality
      data.
AB  - The US health system spends far more on the "technology" of care (e.g., drugs,
      devices) than on achieving equity in its delivery. For 1991 to 2000, we
      contrasted the number of lives saved by medical advances with the number of
      deaths attributable to excess mortality among African Americans. Medical advances
      averted 176,633 deaths, but equalizing the mortality rates of Whites and African
      Americans would have averted 886,202 deaths. Achieving equity may do more for
      health than perfecting the technology of care.

PMID- 15569957
TI  - Association of retail tobacco marketing with adolescent smoking.
AB  - A survey of 2125 middle-school students in central California examined
      adolescents' exposure to tobacco marketing in stores and its association with
      self-reported smoking. Two thirds of sixth-, seventh-, and eighth-grade students
      reported at least weekly visits to small grocery, convenience, or liquor stores.
      Such visits were associated with a 50% increase in the odds of ever smoking, even
      after control for social influences to smoke. Youth smoking rates may benefit
      from efforts to reduce adolescents' exposure to tobacco marketing in stores.

PMID- 15569958
TI  - Patient race/ethnicity and quality of patient-physician communication during
      medical visits.
AB  - OBJECTIVES: We examined the association between patient race/ethnicity and
      patient-physician communication during medical visits. METHODS: We used audiotape
      and questionnaire data collected in 1998 and 2002 to determine whether the
      quality of medical-visit communication differs among African American versus
      White patients. We analyzed data from 458 African American and White patients who
      visited 61 physicians in the Baltimore, Md-Washington, DC-Northern Virginia
      metropolitan area. Outcome measures that assessed the communication process,
      patient-centeredness, and emotional tone (affect) of the medical visit were
      derived from audiotapes coded by independent raters. RESULTS: Physicians were 23%
      more verbally dominant and engaged in 33% less patient-centered communication
      with African American patients than with White patients. Furthermore, both
      African American patients and their physicians exhibited lower levels of positive
      affect than White patients and their physicians did. CONCLUSIONS: Patient
      physician communication during medical visits differs among African American
      versus White patients. Interventions that increase physicians' patient
      centeredness and awareness of affective cues with African Americans patients and
      that activate African American patients to participate in their health care are
      important strategies for addressing racial/ethnic disparities in health care.

PMID- 15569959
TI  - Racial differences in cardiac catheterization as a function of patients' beliefs.
AB  - OBJECTIVES: We examined racial differences in cardiac catheterization rates and
      reviewed whether patients' beliefs or other variables were associated with
      observed disparities. METHODS: We did a prospective observational cohort study of
      1045 White and African American patients at 5 Veterans Affairs (VA) medical
      centers whose nuclear imaging studies indicated reversible cardiac ischemia.
      RESULTS: There were few demographic differences between White and African
      American patients in our sample. African Americans were less likely than Whites
      to undergo cardiac catheterization. African Americans were more likely than
      Whites to indicate a strong reliance on religion and to report racial and social
      class discrimination and were less likely to indicate a generalized trust in
      people but did not differ from White patients on numerous other attitudes about
      health and health care. Neither sociodemographic or clinical characteristics nor
      patients' beliefs explained the observed disparities, but physicians' assessments
      of the procedure's importance and patients' likelihood of coronary disease seemed
      to account for differences not otherwise explained. CONCLUSIONS: Patients'
      preferences are not the likely source of racial disparities in the use of cardiac
      catheterization among veterans using VA care, but physicians' assessments warrant
      further attention.

PMID- 15569960
TI  - Health care disparities and cervical cancer.
AB  - OBJECTIVES: We compared cervical cancer incidence, stage at diagnosis, and
      survival in Medicaid-insured and non-Medicaid-insured populations. METHODS: We
      stratified the sample by age and used ordered logistic regression to predict
      stage at diagnosis and used Cox proportional hazards regression to predict
      survival. RESULTS: Medicaid insured nearly one quarter of women diagnosed with
      cervical cancer. The likelihood of late-stage disease was greatest for women who
      enrolled in Medicaid after diagnosis. Women younger than 65 years who enrolled in
      Medicaid after diagnosis were more likely to die from cervical cancer than were
      women who were not insured by Medicaid (hazard ratio=2.40, 95% confidence
      interval=1.49, 3.86). CONCLUSIONS: Our study underscores the importance of
      cervical cancer screening programs targeted at low-income women.

PMID- 15569961
TI  - Endometrial cancer: socioeconomic status and racial/ethnic differences in stage
      at diagnosis, treatment, and survival.
AB  - OBJECTIVE: We evaluated the association between socioeconomic status and racial/
      ethnic differences in endometrial cancer stage at diagnosis, treatment, and
      survival. METHODS: We conducted a population-based study among 3656 women.
      RESULTS: Multivariate analyses showed that either race/ethnicity or income, but
      not both, was associated with advanced-stage disease. Age, stage at diagnosis,
      and income were independent predictors of hysterectomy. African American
      ethnicity, increased age, aggressive histology, poor tumor grade, and advanced
      stage disease were associated with increased risk for death; higher income and
      hysterectomy were associated with decreased risk for death. CONCLUSIONS: Lower
      income was associated with advanced-stage disease, lower likelihood of receiving
      a hysterectomy, and lower rates of survival. Earlier diagnosis and removal of
      barriers to optimal treatment among lower-socioeconomic status women will
      diminish racial/ethnic differences in endometrial cancer survival.

PMID- 15569962
TI  - Is lipid-lowering therapy underused by African Americans at high risk of coronary
      heart disease within the VA health care system?
AB  - OBJECTIVES: We examined whether racial differences exist in cholesterol
      monitoring, use of lipid-lowering agents, and achievement of guideline
      recommended low-density lipoprotein (LDL) levels for secondary prevention of
      coronary heart disease. METHODS: We reviewed charts for 1045 African American and
      White patients with coronary heart disease at 5 Veterans Affairs (VA) hospitals.
      RESULTS: Lipid levels were obtained in 67.0% of patients. Whites and African
      Americans had similar screening rates and mean lipid levels. Among the 544 ideal
      candidates for therapy, rates of treatment and achievement of target LDL levels
      were similar. CONCLUSIONS: We found no disparities in cholesterol management.
      This absence of disparities may be the result of VA quality improvement
      initiatives or prescription coverage through the VA health care system.

PMID- 15569963
TI  - Experiences of racism among African American parents and the mental health of
      their preschool-aged children.
AB  - OBJECTIVES: We examined the relationship between parents' experiences of racism
      and children's well-being and the influence of the residential neighborhood
      characteristics on this relationship. METHODS: African American families were
      recruited from Baltimore neighborhoods. Parental measures included racism
      experiences and coping. Neighborhood measures included demographic
      characteristics, social cohesion, and social climate. Children's mental health
      was assessed with the Child Behavior Checklist. Analysis was performed with
      multilevel modeling. RESULTS: Parents who denied experiences of racism also
      reported higher rates of behavior problems among their preschool-aged children.
      For families living in neighborhoods characterized by fear of victimization,
      parents who actively coped with racism experiences by confronting the person
      involved or taking some sort of action in response to racism reported lower rates
      of anxiety and depression for their preschool-aged children. CONCLUSIONS:
      Experiences of and responses to racism among African American parents have
      important effects on the well-being of their young children.

PMID- 15569964
TI  - Self-reported experiences of racial discrimination and Black-White differences in
      preterm and low-birthweight deliveries: the CARDIA Study.
AB  - OBJECTIVES: We examined the effects of self-reported experiences of racial
      discrimination on Black-White differences in preterm (less than 37 weeks
      gestation) and low-birthweight (less than 2500 g) deliveries. METHODS: Using
      logistic regression models, we analyzed data on 352 births among women enrolled
      in the Coronary Artery Risk Development in Young Adults Study. RESULTS: Among
      Black women, 50% of those with preterm deliveries and 61% of those with low
      birthweight infants reported having experienced racial discrimination in at least
      3 situations; among White women, the corresponding percentages were 5% and 0%.
      The unadjusted odds ratio for preterm delivery among Black versus White women was
      2.54 (95% confidence interval [CI]=1.33, 4.85), but this value decreased to 1.88
      (95% CI=0.85, 4.12) after adjustment for experiences of racial discrimination and
      to 1.11 (95% CI=0.51, 2.41) after additional adjustment for alcohol and tobacco
      use, depression, education, and income. The corresponding odds ratios for low
      birthweight were 4.24 (95% CI=1.31, 13.67), 2.11 (95% CI=0.75, 5.93), and 2.43
      (95% CI=0.79, 7.42). CONCLUSIONS: Self-reported experiences of racial
      discrimination were associated with preterm and low-birthweight deliveries, and
      such experiences may contribute to Black-White disparities in perinatal outcomes.

PMID- 15569965
TI  - Very low birthweight in African American infants: the role of maternal exposure
      to interpersonal racial discrimination.
AB  - OBJECTIVES: We determined whether African American women's lifetime exposure to
      interpersonal racial discrimination is associated with pregnancy outcomes.
      METHODS: We performed a case-control study among 104 African American women who
      delivered very low birthweight (<1500 g) preterm (<37 weeks) infants and 208
      African American women who delivered non-low-birthweight (>2500 g) term infants
      in Chicago, Ill. RESULTS: The unadjusted and adjusted odds ratio of very low
      birthweight infants for maternal lifetime exposure to interpersonal racism in 3
      or more domains equaled 3.2 (95% confidence intervals=1.5, 6.6) and 2.6 (1.2,
      5.3), respectively. This association tended to persist across maternal
      sociodemographic, biomedical, and behavioral characteristics. CONCLUSIONS: The
      lifelong accumulated experiences of racial discrimination by African American
      women constitute an independent risk factor for preterm delivery.

PMID- 15569966
TI  - An approach to studying social disparities in health and health care.
AB  - OBJECTIVE: We explored methods and potential applications of a systematic
      approach to studying and monitoring social disparities in health and health care.
      METHODS: Using delayed or no prenatal care as an example indicator, we (1)
      categorized women into groups with different levels of underlying social
      advantage; (2) described and graphically displayed rates of the indicator and
      relative group size for each social group; (3) identified and measured
      disparities, calculating relative risks and rate differences to compare each
      group with its a priori most-advantaged counterpart; (4) examined changes in
      rates and disparities over time; and (5) conducted multivariate analyses for the
      overall sample and "at-risk" groups to identify particular factors warranting
      attention. RESULTS: We identified at-risk groups and relevant factors and suggest
      ways to direct efforts for reducing prenatal care disparities. CONCLUSIONS: This
      systematic approach should be useful for studying and monitoring disparities in
      other indicators of health and health care.

PMID- 15569967
TI  - Socioeconomic position and hormone replacement therapy use: explaining the
      discrepancy in evidence from observational and randomized controlled trials.
AB  - OBJECTIVES: We assessed the association between life-course socioeconomic status
      or position (SEP) and hormone replacement therapy (HRT). METHODS: We conducted a
      cross-sectional analysis of 4286 women aged 60 to 79 years. RESULTS: Women
      experiencing adverse socioeconomic circumstances across the life course were less
      likely to have used HRT. The associations of childhood socioeconomic measures
      with HRT use were independent of adult SEP, behavioral risk factors, and
      physiological risk factors for heart disease. CONCLUSIONS: SEP from across the
      life course is associated with HRT use. Because the association between early
      life SEP and HRT is not fully explained by adult risk factors, residual
      confounding (which is not captured by adjustment for adult variables only) may
      explain some of the disparity between observational studies and randomized
      controlled trials in this area.

PMID- 15569968
TI  - Unemployment and early cause-specific mortality: a study based on the Swedish
      twin registry.
AB  - OBJECTIVES: We investigated the association between unemployment and early cause
      specific mortality to determine whether the relationship was modified by other
      risk indicators. METHODS: Female and male twins (n=20632) were followed with
      regard to mortality from 1973 through 1996. Questionnaire data from 1973 were
      used to obtain information on experience of unemployment and on social,
      behavioral, health, and personality characteristics. RESULTS: Unemployment was
      associated with an increased risk of suicide and death from undetermined causes.
      Low education, personality characteristics, use of sleeping pills or
      tranquilizers, and serious or long-lasting illness tended to strengthen the
      association between unemployment and early mortality. CONCLUSIONS: An increased
      risk of death from external causes implies a need for support for those
      experiencing unemployment, particularly susceptible individuals.

PMID- 15569969
TI  - Hurling alone? How social capital failed to save the Irish from cardiovascular
      disease in the United States.
AB  - OBJECTIVES: We performed a historical review of cardiovascular risk profiles of
      Irish immigrants to the United States, 1850-1970, in regard to lifestyle, socio
      economic circumstances, and social capital. METHODS: We analyzed US Census data
      from 1850-1970, area-based social and epidemiological data from Boston, data from
      Ireland's National Nutrition Surveillance Centre, and literature on Irish
      migration. RESULTS: The Irish were consistently at increased risk of
      cardiovascular diseases, a risk that related initially to material deprivation,
      across the life course of at least 2 generations. CONCLUSIONS: The principal
      difference between the Irish and other disadvantaged immigrant groups, such as
      the Italians, was dietary habits influenced by experiences during the Irish
      famine. Although there was a psychosocial component to the disadvantage and
      discrimination they experienced as an ethnic group, the Irish also exhibited
      strong community networks and support structures that might have been expected to
      counteract discrimination's negative effects. However, the Irish's high levels of
      social capital were not protective for cardiovascular disease.

PMID- 15569970
TI  - Socioeconomic disadvantage, parenting responsibility, and women's smoking in the
      United States.
AB  - OBJECTIVES: We carried out analyses of smoking in relation to poverty and child
      care responsibility among women aged 18-54 years residing in the United States.
      METHODS: With data from the Behavioral Risk Factor Surveillance System, we
      assessed the interaction effects of poverty and living with young children on
      maternal smoking behavior among 61,700 women aged 18-54 years in 4 different
      racial/ethnic groups. RESULTS: For non-White racial/ethnic groups, the prevalence
      of smoking among women with small children in the household was lower than that
      among women without small children. However, White women were more likely to
      smoke if they were poor and living with small children (odds ratio=1.14, 95%
      confidence interval=1.03, 1.26). CONCLUSIONS: These results suggest that child
      care responsibility confers an increased risk of smoking among low-income White
      women.

PMID- 15569971
TI  - Prevalence of smoking in 8 countries of the former Soviet Union: results from the
      living conditions, lifestyles and health study.
AB  - OBJECTIVES: We sought to provide comparative data on smoking habits in countries
      of the former Soviet Union. METHODS: We conducted cross-sectional surveys in 8
      former Soviet countries with representative national samples of the population 18
      years or older. RESULTS: Smoking rates varied among men, from 43.3% to 65.3%
      among the countries examined. Results showed that smoking among women remains
      uncommon in Armenia, Georgia, Kyrgyzstan, and Moldova (rates of 2.4%-6.3%). In
      Belarus, Ukraine, Kazakhstan, and Russia, rates were higher (9.3%-15.5%). Men
      start smoking at significantly younger ages than women, smoke more cigarettes per
      day, and are more likely to be nicotine dependent. CONCLUSIONS: Smoking rates
      among men in these countries have been high for some time and remain among the
      highest in the world. Smoking rates among women have increased from previous
      years and appear to reflect transnational tobacco company activity.

PMID- 15569972
TI  - Undoing an epidemiological paradox: the tobacco industry's targeting of US
      Immigrants.
AB  - OBJECTIVES: We sought to ascertain whether the tobacco industry has
      conceptualized the US immigrant population as a separate market. METHODS: We
      conducted a content analysis of major tobacco industry documents. RESULTS: The
      tobacco industry has engaged in 3 distinct marketing strategies aimed at US
      immigrants: geographically based marketing directed toward immigrant communities,
      segmentation based on immigrants' assimilation status, and coordinated marketing
      focusing on US immigrant groups and their countries of origin. CONCLUSIONS:
      Public health researchers should investigate further the tobacco industry's
      characterization of the assimilated and non-assimilated immigrant markets, and
      its specific strategies for targeting these groups, in order to develop informed
      national and international tobacco control countermarketing strategies designed
      to protect immigrant populations and their countries of origin.

PMID- 15569973
TI  - Recurrent ovarian cancer: how important is it to treat to disease progression?
AB  - Ovarian cancer is increasingly recognized as a chronic disease whose treatment is
      often characterized by administration of multiple, sequential active agents, each
      of which may or may not be accompanied by a tumor response. Despite the large
      proportion of patients who relapse and undergo longer-term treatment, the
      question of optimal treatment duration has not been fully addressed to date. For
      patients who progress on therapy, the answer is straightforward: they are
      switched to another active agent, presumably having a different mechanism of
      action from previous therapies with, ideally, limited overlapping toxicities.
      However, for patients who remain in partial response or who have stable disease,
      the answer is less apparent and less clear. The majority of oncologists believe
      that treatment beyond 6 cycles of a given therapy does not provide any additional
      benefit to patients. There are some data to support that treatment strategy.
      However, with the advent of new, less toxic agents, treatment to progression
      should be further explored. Agents that are potentially well suited for extended
      treatment intervals may include such properties as absence of cumulative
      toxicity, non-cross-resistance, positive benefit on quality of life, and
      convenient schedule. A number of active agents in ovarian cancer (platinum,
      paclitaxel, topotecan, liposomal doxorubicin, docetaxel, gemcitabine, and
      etoposide) will be reviewed in the context of what is known about cumulative
      toxicity, potential adverse effects on patients' quality of life, and evidence
      addressing the potential benefits of longer-term treatment.

PMID- 15569974
TI  - A phase I trial of perifosine (NSC 639966) on a loading dose/maintenance dose
      schedule in patients with advanced cancer.
AB  - Perifosine (NSC 639966) is a synthetic, substituted heterocyclic
      alkylphosphocholine that acts primarily at the cell membrane targeting signal
      transduction pathways. Early clinical trials were limited because of dose
      limiting gastrointestinal toxicity, and parenteral dosing of this class of agents
      is not possible because of their hemolytic properties; therefore, related
      compounds with an improved therapeutic index were developed. Toxicity was
      minimized and efficacy improved by using a loading dose/maintenance dose
      schedule, and therefore, this schedule was carried into clinical trials. This
      phase I trial enrolled 42 patients with incurable solid malignancies. The
      starting doses were 100 mg p.o. x four doses (every 6 hours) load followed by a
      50 mg p.o. once daily maintenance dose with escalation of either component in
      successive dose levels. No treatment related deaths occurred. The maximum
      tolerated dose was determined to be 150 mg p.o. x four doses load and 100 mg p.o.
      once daily maintenance. Dose-limiting toxicities such as nausea, diarrhea,
      dehydration, and fatigue were seen early during the loading phase and were
      surmountable with the use of prophylactic 5-HT3 receptor antagonists,
      dexamethasone, and loperamide. Toxicities during the chronic phase were difficult
      to manage and, given that pharmacokinetic data showed biologically active serum
      concentrations (based on preclinical data), raised the question of less frequent
      maintenance dosing. Pharmacokinetic data confirmed the maintenance of stable drug
      levels with chronic dosing and the long half-life. One partial response was seen,
      as were multiple patients with stable disease beyond course 2. These results
      suggest perifosine activity in sarcoma and perhaps renal cell carcinoma (stable
      disease in two patients who continued for 6 and 14 courses), thus justifying
      additional investigation of this agent in a phase II sarcoma trial.

PMID- 15569975
TI  - Detection of methylated apoptosis-associated genes in urine sediments of bladder
      cancer patients.
AB  - PURPOSE: There is increasing evidence for a fundamental role for epigenetic
      silencing of apoptotic pathways in cancer. Changes in DNA methylation can be
      detected with a high degree of sensitivity, so we used the MethyLight assay to
      determine how methylation patterns of apoptosis-associated genes change during
      bladder carcinogenesis and whether DNA methylation could be detected in urine
      sediments. EXPERIMENTAL DESIGN: We analyzed the methylation status of the 5'
      regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK,
      TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines,
      127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa
      using the quantitative MethyLight assay. We also analyzed the methylation status
      in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients.
      RESULTS: The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed
      significant increases in methylation levels when compared with nonmalignant
      adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly
      associated with tumor staging and grading (P < or = 0.01), whereas methylation
      levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04),
      and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or
      = 0.02). To investigate clinical usefulness for noninvasive bladder cancer
      detection, we further analyzed the methylation status of the markers in urine
      samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in
      urine sediment DNA from bladder cancer patients was detected in the majority of
      samples (78%), whereas they were unmethylated in the urine sediment DNA from age
      matched cancer-free individuals. CONCLUSIONS: Our results indicate that
      methylation of the 5' region of apoptosis-associated genes is a common finding in
      patients with bladder carcinoma. The ability to detect methylation not only in
      bladder tissue, but also in urine sediments, suggests that methylation markers
      are promising tools for noninvasive detection of bladder cancers. Our results
      also indicate that some methylation markers, such as those in regions of RASSF1A
      and TNFRSF25, might be of limited use for detection because they are also
      methylated in normal bladder tissues.

PMID- 15569976
TI  - Dendritic cell infiltration and prognosis of early stage breast cancer.
AB  - PURPOSE: Although dendritic cells (DC) and T cells can infiltrate primary breast
      carcinoma, it remains unclear whether the immune response influences the clinical
      outcome. EXPERIMENTAL DESIGN: T lymphocytes and DC infiltration within primary
      tumors was investigated in 152 patients with invasive nonmetastatic breast
      cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was
      assessed with semiquantitative immunohistochemical analysis. Expression of
      chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and
      6Ckine/CCL21) was also examined. The correlation between these markers and the
      characteristics of the tumors, as well as relapse-free and overall survival was
      analyzed. Significant prognostic parameters were then tested in a validation
      series. RESULTS: Infiltration by immature CD207/Langerin+ DC was found in a third
      of the cancers and did not correlate with clinicopathological data. Presence of
      mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with
      lymph node involvement and tumor grade. Among the chemokines analyzed, only the
      presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall
      survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors.
      Their presence was strongly associated with shorter overall survival (93% versus
      58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was
      found to be an independent prognostic factor for overall survival and relapse
      free survival and confirmed in an independent validation series of 103 patients.
      CONCLUSIONS: Infiltration by pDC of primary localized breast tumor correlates
      with an adverse outcome, suggesting their contribution in the progression of
      breast cancer.

PMID- 15569977
TI  - Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor
      differentiation and unfavorable prognosis.
AB  - PURPOSE: ID4 gene is a member of the inhibitor of DNA binding (ID) family
      proteins that inhibit DNA binding of basic helix-loop-helix transcription
      factors. The epigenetic inactivation of ID4 gene on colorectal cancer (CRC)
      development and its clinical significance was assessed. EXPERIMENTAL DESIGN: In
      CRC cell lines, ID4 methylation status of the promoter region was assessed by
      methylation-specific PCR and bisulfite sequencing. The mRNA expression level was
      assessed by quantitative real-time reverse transcription-PCR. The methylation
      status of 9 normal epithelia, 13 adenomas, 92 primary CRCs, and 26 liver
      metastases was assessed by methylation-specific PCR. ID4 protein expression was
      assessed by immunohistochemistry analysis of tissue specimen. RESULTS: CRC cell
      lines were shown to be hypermethylated, and mRNA expression was suppressed and
      could be restored by 5-aza-cytidine treatment. In clinical specimens from normal
      epithelia, adenomas, primary CRCs, and liver metastases, the frequency of ID4
      hypermethylation was 0 of 9 (0%), 0 of 13 (0%), 49 of 92 (53%), and 19 of 26
      (73%), respectively, with a significant elevation according to CRC pathological
      progression. Methylation status of primary CRCs significantly correlated with
      histopathological tumor grade (P = 0.028). Immunohistochemistry analysis showed
      ID4 expression of normal colon epithelia, adenomas, and unmethylated primary CRCs
      but not hypermethylated CRC specimens. Among 76 American Joint Committee on
      Cancer stage I to IV patients who had undergone curative surgical resection,
      overall survival was significantly poorer in patients with hypermethylated ID4
      bearing tumors (P = 0.0066). CONCLUSIONS: ID4 gene is a potential tumor
      suppressor gene for which methylation status may play an important role in the
      CRC progression.

PMID- 15569978
TI  - p16INK4A hypermethylation is associated with hepatitis virus infection, age, and
      gender in hepatocellular carcinoma.
AB  - PURPOSE: The tumor suppressor gene p16INK4A is mainly inactivated by an
      epigenetic change involving promoter hypermethylation in hepatocarcinogenesis.
      The possible clinical impact of p16INK4A methylation and the potential risk
      factors for this epigenetic alteration have not been thoroughly investigated.
      EXPERIMENTAL DESIGN: We studied the methylation status and mRNA and protein
      expression of p16INK4A in 50 hepatocellular carcinomas and corresponding
      nonneoplastic liver lesions using methylation-specific PCR, reverse transcription
      PCR, and immunohistochemical techniques. RESULTS: p16INK4A hypermethylation was
      observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of
      the corresponding chronic hepatitis and cirrhosis tissue samples. p16INK4A
      methylation was significantly associated with mRNA and protein expression (P
      <0.001 and P=0.003, respectively). All of the p16INK4A-methylated tumors were
      positive for hepatitis B virus or hepatitis C virus markers, but none of the
      virus-negative tumors exhibited p16INK4A methylation (P=0.006). The frequency of
      p16INK4A hypermethylation tended to be higher in hepatitis C virus-related tumors
      (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P=0.1).
      Aberrant methylation of p16INK4A was also related significantly to increasing
      age, female gender, and normal levels of serum PIVKA-II (P=0.02, 0.04, and 0.04,
      respectively). No statistically significant difference in survival was observed
      between patients with p16INK4A hypermethylation and those without. CONCLUSIONS:
      Our observations suggest that p16INK4A hypermethylation may contribute to
      hepatocarcinogenesis from an early stage and that multiple risk factors, such as
      viral infections, age, and gender, may be associated with p16INK4A
      hypermethylation in hepatocarcinogenesis.

PMID- 15569979
TI  - Low levels of estrogen receptor beta protein predict resistance to tamoxifen
      therapy in breast cancer.
AB  - PURPOSE: Breast cancer is a hormone-dependent cancer, and the presence of
      estrogen receptor alpha (ER-alpha) in tumors is used clinically to predict the
      likelihood of response to hormonal therapies. The clinical value of the second
      recently identified ER isoform, called ER-beta, is less clear, and there is
      currently conflicting data concerning its potential role as a prognostic or
      predictive factor. EXPERIMENTAL DESIGN: To assess whether ER-beta expression is
      associated with clinical outcome, protein levels were measured by immunoblot
      analysis of a retrospective bank of tumor cell lysates from 305 axillary node
      positive patients. A total of 119 received no adjuvant therapy, and 186 were
      treated with tamoxifen only. The median follow-up time was 65 months. Univariate
      and multivariate Cox regression modeling was done to assess the prognostic and
      predictive significance of ER-beta expression. RESULTS: Expression of ER-beta
      protein did not correlate significantly with any other clinical variables,
      including ER and progesterone levels (as measured ligand binding assay), tumor
      size, age, or axillary nodal status. In the untreated population, those patients
      whose tumors who expressed both receptor isoforms exhibited the most favorable
      outcome as compared with those patients who had lost ER-alpha expression.
      However, there was no association between ER-beta levels alone and either disease
      free or overall survival in the untreated patient population. In contrast, in
      both univariate and multivariate analyses, high levels of ER-beta predicted an
      improved disease-free and overall survival in patients treated with adjuvant
      tamoxifen therapy. CONCLUSIONS: These findings provide evidence that ER-beta may
      be an independent predictor of response to tamoxifen in breast cancer.
      Furthermore, these results suggest that ER-beta may influence tumor progression
      in ways different from those mediated by the ER-alpha isoform.

PMID- 15569980
TI  - Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid.
AB  - PURPOSE: Proteomic analysis of breast nipple aspirate fluid (NAF) holds promise
      as a noninvasive method to identify markers of breast cancer. The objectives of
      the study were to: (a) describe the NAF proteome, (b) identify candidate markers
      of breast cancer in NAF by using proteomic analysis, and (c) validate the markers
      identified by using a quantitative, high-throughput ELISA analysis. EXPERIMENTAL
      DESIGN: For proteome analysis, NAF proteins from a single subject without breast
      cancer were separated by two-dimensional PAGE and were subjected to matrix
      assisted laser desorption ionization time-of-flight mass spectometry
      identification. A total of 41 different proteins were identified, 25 of which
      were known to be secreted. To identify breast cancer markers, we separated 20 NAF
      samples (10 normal, 10 cancer) by two-dimensional PAGE. Three protein spots were
      detected that were up-regulated in three or more cancer samples. These spots were
      identified to be gross cystic disease fluid protein (GCDFP)-15, apolipoprotein D
      (apoD), and alpha1-acid glycoprotein (AAG). To validate these three potential
      biomarkers, 105 samples (53 from benign breasts and 52 from breasts with cancer)
      were analyzed using ELISA. RESULTS: Among all of the subjects, GCDFP-15 levels
      were lower (P <0.001) and AAG levels were higher (P=0.001) in breasts with
      cancer. This was also true in premenopausal (GCDFP-15, P=0.011; AAG, P=0.002) but
      not in postmenopausal women. GCDFP-15 levels were lowest (P=0.003) and AAG levels
      highest (P <0.001) in women with ductal carcinoma in situ (DCIS). Menopausal
      status influenced GCDFP-15 and AAG more in women without breast cancer than in
      women with breast cancer. apoD levels did not correlate significantly with breast
      cancer. CONCLUSIONS: Our study revealed that the NAF proteome, as defined by two
      dimensional PAGE, consists of a limited number of proteins, and that the
      expression of AAG and GCDFP-15 correlates with disease presence and stage.

PMID- 15569981
TI  - The use of real-time reverse transcription-PCR for prostate-specific antigen mRNA
      to discriminate between blood samples from healthy volunteers and from patients
      with metastatic prostate cancer.
AB  - PURPOSE: A clinical role for nonquantitative reverse transcription-PCR (RT-PCR)
      using prostate-specific antigen in blood samples from patients with prostate
      cancer remains undefined. Assay variation and detection of prostate-specific
      antigen mRNA illegitimate transcription may explain inconsistent results between
      studies. Defining levels of prostate-specific antigen mRNA expression in blood
      samples from healthy volunteers and patients with prostate cancer would allow
      cutoffs to be established to distinguish the two groups. EXPERIMENTAL DESIGN:
      Quantitative real-time RT-PCR for prostate-specific antigen mRNA was established
      and levels of prostate-specific antigen mRNA measured in bloods samples from
      healthy volunteers (n=21) and patients with localized (n=27) and metastatic
      (n=40) prostate cancer. RESULTS: Levels of prostate-specific antigen mRNA were
      significantly higher in blood samples from patients with metastatic prostate
      cancer than in blood samples from patients with localized prostate cancer (P
      <0.001) or in blood samples from healthy volunteers (P <0.01); levels between
      patients with localized prostate cancer and healthy volunteers were no different.
      Assay sensitivity to detect patients with metastatic prostate cancer was 68% with
      specificity of 95%. In patients with newly diagnosed metastatic prostate cancer,
      monitoring response to hormonal therapy was possible with this assay. No
      correlation between levels of prostate-specific antigen mRNA and serum prostate
      specific antigen protein levels was found, suggesting that prostate-specific
      antigen mRNA and serum prostate-specific antigen protein levels reflect different
      features of prostate cancer, i.e., circulating tumor cells and total tumor bulk,
      respectively. CONCLUSIONS: Quantitative RT-PCR discriminates patients with
      metastatic prostate cancer from healthy volunteers and patients with localized
      prostate cancer but cannot discriminate patients with localized prostate cancer
      from healthy volunteers. A role for quantitative RT-PCR has been identified in
      the assessment and monitoring of patients with metastatic prostate cancer.

PMID- 15569982
TI  - Differential radiosensitization in DNA mismatch repair-proficient and -deficient
      human colon cancer xenografts with 5-iodo-2-pyrimidinone-2'-deoxyribose.
AB  - PURPOSE: 5-iodo-2-pyrimidinone-2'-deoxyribose (IPdR) is a pyrimidinone nucleoside
      prodrug of 5-iododeoxyuridine (IUdR) under investigation as an orally
      administered radiosensitizer. We previously reported that the mismatch repair
      (MMR) proteins (both hMSH2 and hMLH1) impact on the extent (percentage) of IUdR
      DNA incorporation and subsequent in vitro IUdR-mediated radiosensitization in
      human tumor cell lines. In this study, we used oral IPdR to assess in vivo
      radiosensitization in MMR-proficient (MMR+) and -deficient (MMR-) human colon
      cancer xenografts. EXPERIMENTAL DESIGN: We tested whether oral IPdR treatment (1
      g/kg/d for 14 days) can result in differential IUdR incorporation in tumor cell
      DNA and subsequent radiosensitization after a short course (every day for 4 days)
      of fractionated radiation therapy, by using athymic nude mice with an isogenic
      pair of human colon cancer xenografts, HCT116 (MMR-, hMLH1-) and HCT116/3-6
      (MMR+, hMLH1+). A tumor regrowth assay was used to assess radiosensitization.
      Systemic toxicity was assessed by daily body weights and by percentage of IUdR
      DNA incorporation in normal bone marrow and intestine. RESULTS: After a 14-day
      once-daily IPdR treatment by gastric gavage, significantly higher IUdR-DNA
      incorporation was found in HCT116 (MMR-) tumor xenografts compared with HCT116/3
      6 (MMR+) tumor xenografts. Using a tumor regrowth assay after the 14-day drug
      treatment and a 4-day radiation therapy course (days 11-14 of IPdR), we found
      substantial radiosensitization in both HCT116 and HCT116/3-6 tumor xenografts.
      However, the sensitizer enhancement ratio (SER) was substantially higher in
      HCT116 (MMR-) tumor xenografts (1.48 at 2 Gy per fraction, 1.41 at 4 Gy per
      fraction), compared with HCT116/3-6 (MMR+) tumor xenografts (1.21 at 2 Gy per
      fraction, 1.20 at 4 Gy per fraction). No substantial systemic toxicity was found
      in the treatment groups. CONCLUSIONS: These results suggest that IPdR-mediated
      radiosensitization can be an effective in vivo approach to treat "drug-resistant"
      MMR-deficient tumors as well as MMR-proficient tumors.

PMID- 15569983
TI  - The CC chemokine receptor 4 as a novel specific molecular target for
      immunotherapy in adult T-Cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal
      prognosis, and no optimal therapy has been developed. We tested the defucosylated
      chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to
      develop a novel immunotherapy for this refractory tumor. In the presence of
      peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760
      induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against
      CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL
      patients. We next examined the KM2760-induced ADCC against primary ATLL cells in
      an autologous setting. Antibody-dependent cellular cytotoxicity mediated by
      autologous effector cells was generally lower than that mediated by allogeneic
      control effector cells. However, a robust ADCC activity was induced in some
      cases, which was comparable with that mediated by allogeneic effector cells. It
      suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function,
      although the optimal conditions for maximal effect have not yet been determined.
      In addition, we also found a high expression of FoxP3 mRNA and protein, a
      hallmark of regulatory T cells, in ATLL cells, indicating the possibility that
      ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA
      expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in
      vitro. Our data suggest not only that the CCR4 molecule could be a suitable
      target for the novel antibody-based therapy for patients with ATLL but also that
      KM2760 may induce effective tumor immunity by reducing the number of regulatory T
      cells.

PMID- 15569984
TI  - Transforming growth factor beta receptor I kinase inhibitor down-regulates
      cytokine secretion and multiple myeloma cell growth in the bone marrow
      microenvironment.
AB  - PURPOSE: Transforming growth factors (TGFs) have pleiotropic biological effects
      on tumor cells and their environment. In multiple myeloma (MM), we have reported
      that bone marrow stromal cells (BMSCs) from MM patients produce more TGF-beta1
      than BMSCs from healthy donors, which in turn induces interleukin (IL)-6
      secretion. We show here that the TGF-beta receptor I kinase inhibitor SD-208
      significantly decreases secretion of both IL-6 and vascular endothelial growth
      factor (VEGF) from BMSCs, as well as tumor cell growth triggered by MM cell
      adhesion to BMSCs. EXPERIMENTAL DESIGN: Cytokine production and MM cell
      proliferation triggered by TGF-beta1 or adhesion to BMSCs were examined in the
      presence or absence of SD-208. Effects of SD-208 on TGF-beta1-induced signaling
      pathways triggering IL-6 and VEGF transcription in BMSCs were also delineated.
      RESULTS: SD-208 significantly inhibits not only transcription but also secretion
      of both IL-6 and VEGF from BMSCs triggered by either TGF-beta1 or adhesion of MM
      cells to BMSCs. Moreover, SD-208 decreased tumor cell growth triggered by MM cell
      adhesion to BMSCs. SD-208 works, at least in part, by blocking TGF-beta1
      triggered nuclear accumulation of Smad2/3 and hypoxia-inducible factor 1alpha, as
      well as related production of IL-6 and VEGF, respectively. CONCLUSIONS: These
      studies indicate that SD-208 inhibits production of cytokines mediating MM cell
      growth, survival, drug resistance, and migration in the BM milieu, thereby
      providing the preclinical rationale for clinical evaluation of SD-208 to improve
      patient outcome in MM.

PMID- 15569985
TI  - Epidermal growth factor receptor tyrosine kinase inhibition represses cyclin D1
      in aerodigestive tract cancers.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) are active in cancer therapy. Mechanisms engaged during these clinical
      responses need to be determined. We reported previously that epidermal growth
      factor stimulation markedly increased cyclin D1 protein expression in human
      bronchial epithelial (HBE) cells, and this was opposed by chemoprevention with
      all-trans-retinoic acid. The current study sought to determine whether the EGFR
      TKI erlotinib repressed cyclin D1 protein expression in immortalized HBE cells,
      lung cancer cell lines, and clinical aerodigestive tract cancers. EXPERIMENTAL
      DESIGN: The BEAS-2B immortalized HBE cell line was exposed to varying
      concentrations of erlotinib, and effects on proliferation, cell cycle
      distribution, G1 cyclin expression, and cyclin D1 reporter activity were
      measured. Non-small-cell lung cancer cell lines were also evaluated for changes
      in proliferation and cyclin protein expression after erlotinib treatments. A
      proof of principle clinical trial was conducted. During this study, patients
      underwent a 9-day course of erlotinib treatment. Pretreatment and posttreatment
      tumor biopsies were obtained, and changes in candidate biomarkers were determined
      by immunostaining. Plasma pharmacokinetics and tumor tissue erlotinib
      concentrations were measured. RESULTS: Erlotinib, at clinically achievable
      dosages, repressed BEAS-2B cell growth, triggered G1 arrest, and preferentially
      reduced cyclin D1 protein expression and transcriptional activation. Erlotinib
      also preferentially repressed proliferation and cyclin D1 protein expression in
      responsive, but not resistant, non-small-cell lung cancer cell lines. This
      occurred in the presence of wild-type EGFR sequence at exons 18, 19, and 21. Five
      patients were enrolled onto an erlotinib proof of principle clinical trial, and
      four cases were evaluable. Pharmacokinetic studies established therapeutic
      erlotinib plasma levels in all patients, but tissue levels exceeding 2 micromol/L
      were detected in only two cases. Notably, these cases had pathological evidence
      of response (necrosis) in posttreatment biopsies as compared with pretreatment
      biopsies. In these cases, marked repression of cyclin D1 and the proliferation
      marker Ki-67 was detected by immunohistochemical assays. Cases without
      pathological response to erlotinib did not exhibit changes in cyclin D1 or Ki-67
      immunohistochemical expression and had much lower erlotinib tissue levels than
      did responding cases. CONCLUSIONS: Taken together, these in vitro and in vivo
      findings provide direct evidence for repression of cyclin D1 protein as a
      surrogate marker of response in aerodigestive tract cancers to erlotinib
      treatment. These findings also provide a rationale for combining an EGFR TKI with
      an agent that would cooperatively repress cyclin D1 expression in clinical trials
      for aerodigestive tract cancer therapy or chemoprevention.

PMID- 15569986
TI  - ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced
      adenocarcinomas.
AB  - PURPOSE: To determine the feasibility of administration, safety, toxicity,
      immunogenicity, pharmacokinetics, maximum tolerated dose, and biodistribution of
      ING-1, a high-affinity, Human-Engineered monoclonal antibody (heMAb) to the Mr
      40,000 epithelial cell adhesion molecule Ep-CAM, in patients with advanced
      adenocarcinomas. EXPERIMENTAL DESIGN: ING-1 was initially administered to
      patients as a 1-hour intravenous infusion every 3 weeks. Toxicity and
      pharmacokinetic data led to the evaluation of a weekly schedule. The distribution
      of iodine-131 (131I)-labeled ING-1 was studied. RESULTS: Twenty-five patients
      received 82 courses of ING-1. Minimal toxicity was initially observed at the 0.03
      , 0.10-, and 0.30-mg/kg dose levels. A patient dosed at 1.0 mg/kg developed acute
      pancreatitis with severe abdominal pain, nausea, and vomiting. A patient dosed at
      0.3 mg/kg had an asymptomatic amylase and lipase elevation to 502 units/L and
      1,627 units/L, respectively. Both patients made uncomplicated recoveries. No
      other dose-limiting toxicities were observed. Regardless of dose, the volume of
      distribution (mean +/- SEM) was 46.6 +/- 1.6 mL/kg. ING-1 clearance decreased
      with increasing dose. To minimize toxicity and increase dose intensity, we then
      administered ING-1 weekly. No significant toxicity was observed in 7 patients
      dosed at 0.1 mg/kg. Studies of 131I-labeled ING-1 biodistribution showed
      radiolocalization to colorectal and prostate cancers. A patient with colorectal
      cancer had an 80% decrement in the levels of carcinoembryonic antigen.
      CONCLUSION: The recommended dose for ING-1 is 0.10 mg/kg by intravenous infusion
      weekly. The absence of severe toxicity at this dose, low immunogenicity, and
      preliminary evidence of ING-1 tumor localization and antitumor efficacy support
      the further clinical development of this antibody to treat Ep-CAM-positive
      malignant diseases.

PMID- 15569987
TI  - Characterization and multiparameter analysis of visual adverse events in
      irofulven single-agent phase I and II trials.
AB  - PURPOSE: Irofulven (6-hydroxymethylacylfulvene) is a novel agent, derived from
      illudin S, with potent apoptotic effects in preclinical models. In the Phase I
      trial evaluating intermittent weekly schedules, visual symptoms were dose
      limiting. The aim of this analysis was to better characterize the visual adverse
      events of irofulven and provide treatment guidelines. EXPERIMENTAL DESIGN:
      Clinical data from 277 patients entered in single-agent Phase I to II clinical
      trials who received irofulven on days 1 and 15 every 4 weeks; days 1, 8, and 15
      every 4 weeks; or days 1 and 8 every 3 weeks were included in this multiparameter
      analysis. RESULTS: Overall, 74 patients (27%) experienced visual symptoms. The
      most frequently reported symptoms were flashing lights (12% of patients), blurred
      vision (9%), and photosensitivity (8%). Grade 3 toxicity was observed in 12
      patients (4%). The incidence and severity of visual events were dose dependent,
      with no grade 3 visual events occurring at doses < or =0.50 mg/kg and grade 1 to
      2 events in only 12% and 8% of patients, at doses of < or =0.50 mg/kg and < or
      =20 mg/m2, respectively. Grade 1 to 2 toxicity was reversible in most patients.
      Abnormal electroretinogram and abnormal visual fields were noted after irofulven
      treatment in 24 of 39 patients (62%) and 15 of 26 patients (58%), respectively.
      All but 1 patient who had electroretinogram assessment received doses >0.50
      mg/kg. Clinical examination and visual field assessment were found to be better
      correlated with symptoms and appear to be more appropriate for surveillance of
      irofulven retinal symptoms than electroretinograms. CONCLUSIONS: On the basis of
      retained antitumor activity and reversibility of grade 1 and 2 visual symptoms at
      lower doses, it appears that an irofulven dose of < or =0.50 mg/kg or < or =20
      mg/m2, not to exceed 50 mg in a single dose, given as a 30-minute infusion on
      days 1 and 8 every 3 weeks or days 1 and 15 every 4 weeks minimizes the frequency
      and severity of visual symptoms.

PMID- 15569988
TI  - Associations between serum testosterone fall and cognitive function in prostate
      cancer patients.
AB  - Data on the association between cognition and testosterone levels in elderly men
      are inconclusive. Androgen deprivation therapy is commonly used in the treatment
      of prostate cancer with the aim of achieving castration levels of serum
      testosterone. The study group comprised 26 elderly men (mean age 65 years) with
      newly diagnosed prostate cancer. Cognitive testing was done at baseline and at 6
      and 12 months on androgen deprivation therapy. Cognitive performances were
      evaluated using verbal, visuomotor, and memory tests as well as tests of
      processing speed and attention. Castration levels of testosterone were achieved
      in all patients by 6 months. Significant associations between cognitive
      performances and testosterone decline were documented: visuomotor slowing, slowed
      reaction times in some attentional domains including working memory and impaired
      hit rate in a vigilance test, impaired delayed recall and recognition speed of
      letters, but improvement in object recall. The results suggest selective
      associations between testosterone decline and cognition. Documentation of
      cognitive performance with changes in serum testosterone levels has substantial
      implications for informed patient support in prostate cancer.

PMID- 15569989
TI  - A pilot surrogate end point biomarker trial of perillyl alcohol in breast
      neoplasia.
AB  - PURPOSE: Efficient strategies to screen promising agents in early phase
      development are essential for rapid progress in breast cancer chemoprevention. We
      report our experience with the natural compound perillyl alcohol (POH)
      administered in a short-term surrogate end point biomarker (SEB) protocol, using
      the "window" between diagnostic and definitive surgery. EXPERIMENTAL DESIGN:
      Eligible patients included those with a diagnosis of atypical ductal hyperplasia,
      ductal carcinoma in situ, lobular carcinoma in situ, or invasive carcinoma (<3 cm
      in size) that required further surgery. Thirty-seven of 267 women screened were
      enrolled in the study (14%). Five women received single-dose POH (1.5 g/m2) 2
      days before surgery, 16 received escalating doses of POH (1.2 g/m2 to 4.8
      g/m2/day) for 2 days before surgery, and 16 served as untreated controls.
      Exploratory SEB analysis [estrogen receptor, progesterone receptor,
      proliferation, apoptosis, M6P/insulin-like growth factor (IGF)-2R, IGF1, IGF2 and
      transforming growth factor beta] was conducted before and after POH. RESULTS:
      Only a small portion of the population screened entered the study. Reasons for
      nonparticipation included protocol ineligibility, conflict of timing of surgery,
      miscellaneous logistical reasons, or patient's choice. POH administration was
      well tolerated and did not interfere with surgical management. The power to
      observe changes in candidate SEB was diminished by a 44% incidence of cases in
      which the index lesion was not present in the definitive surgical specimen.
      CONCLUSIONS: Preoperative POH exposure was safe and suitable for a more
      definitive phase II SEB study. Further investigations must overcome logistical
      obstacles to accrual, and they must focus on approaches to maximize tissue
      collection and to incorporate genomic analysis of target lesions.

PMID- 15569990
TI  - Methylenetetrahydrofolate reductase genotype affects risk of relapse after
      hematopoietic cell transplantation for chronic myelogenous leukemia.
AB  - PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) directs intracellular folate
      toward homocysteine metabolism and away from nucleotide synthesis. Two common
      MTHFR polymorphisms, C677T and A1298C, are associated with reduced enzyme
      activity. We evaluated the association of these polymorphisms with risk of
      relapse and bcr-abl mRNA transcript detection among 336 Caucasian patients who
      underwent allogeneic hematopoietic cell transplantation for chronic myelogenous
      leukemia. EXPERIMENTAL DESIGN: Data on the transplant course and folate-related
      exposures were abstracted from medical records. MTHFR C677T and A1298C genotypes
      were determined using polymerase chain reaction/restriction fragment length
      polymorphism and TaqMan assays. Qualitative bcr-abl mRNA testing was conducted
      using a two-step reverse transcription-polymerase chain reaction assay. Cox
      regression analysis was used to assess the association between MTHFR genotypes
      and time to relapse and bcr-abl mRNA detection. RESULTS: A statistically
      significant decreased risk of relapse was observed in patients with the variant
      A1298C genotype [1298AC, hazard ratio (HR)=0.48 and 95% confidence interval
      (CI)=0.26-0.88; 1298CC, HR=0.28 and 95% CI=0.09-0.84; P-trend <0.01). For the
      joint C677T/A1298C genotype, variant genotypes were associated with a decreased
      risk of relapse when compared with the wild-type 677CC/1298AA genotype. This risk
      was lowest for the 677CC/1298CC genotype (HR, 0.23; 95% CI, 0.08-0.72). MTHFR
      genotypes were not associated with bcr-abl transcript detection. CONCLUSIONS:
      These findings suggest that individuals with the 677CC/1298AA genotype are at
      higher risk of relapse after hematopoietic cell transplantation and that the
      balance of intracellular folate metabolites available for nucleotide synthesis
      (regulated by the relative activity of the MTHFR enzyme) may affect the
      progression from bcr-abl positivity to clinical relapse.

PMID- 15569991
TI  - CD34+ cells from acute myeloid leukemia, myelodysplastic syndromes, and normal
      bone marrow display different apoptosis and drug resistance-associated
      phenotypes.
AB  - Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous
      disorders in which conflicting results in apoptosis and multidrug resistance
      (MDR) have been reported. We have evaluated by multiparameter flow cytometry the
      expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P
      glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance
      protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32
      /dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome
      (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and
      compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high
      risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P
      <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk
      myelodysplastic syndrome and normal controls. Similar results applied to the two
      predefined CD34+ myeloid cell subsets. No significant differences were found in
      the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome
      patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high
      risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic
      syndromes were detected. Hierarchical clustering analysis showed that low-risk
      myelodysplastic syndrome patients were clustered next to normal BM samples,
      whereas high-risk myelodysplastic syndromes were clustered together and mixed
      with the de novo AML patients. In summary, increased resistance to chemotherapy
      of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be
      explained more appropriately in terms of an increased antiapoptotic phenotype
      rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally
      high apoptotic rates would be restricted to the CD34- cell compartments.

PMID- 15569992
TI  - Inactivation of the FHIT gene favors bladder cancer development.
AB  - The fragile histidine triad (FHIT) gene located on chromosome 3p14.2 is
      frequently deleted in human tumors. We have previously reported deletions at the
      FHIT locus in 50% of bladder carcinoma derived cell lines and reduced expression
      in 61% of primary transitional carcinomas of the urinary bladder. To additionally
      investigate the role of FHIT alterations in the development of bladder cancer, we
      used heterozygous and nullizygous Fhit-deficient mice in a chemically induced
      carcinogenesis model. Results showed that 8 of 28 (28%) and 6 of 13 (46%) of the
      Fhit -/- and +/-, respectively, versus 2 of 25 (8%) Fhit +/+ mice developed
      invasive carcinoma after treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine.
      To explore the possibility of a FHIT-based gene therapy for bladder cancer, we
      studied the effects of restored Fhit protein expression on cell proliferation,
      cell kinetics, and tumorigenicity in BALB/c nude mice, with human SW780 Fhit-null
      transitional carcinoma derived cells. In vitro transduction of SW780 Fhit
      negative cells with adenoviral-FHIT inhibited cell growth, increased apoptotic
      cell population, and suppressed s.c. tumor growth in nude mice. These findings
      suggest the important role of Fhit in bladder cancer development and support the
      effort to additionally investigate a FHIT-based gene therapy.

PMID- 15569993
TI  - A clinicobiological model predicting survival in medulloblastoma.
AB  - PURPOSE: The purpose of this study was to determine the relative contributions of
      biological and clinical predictors of survival in patients with medulloblastoma
      (MB). EXPERIMENTAL DESIGN: Clinical presentation and survival information were
      obtained for 119 patients who had undergone surgery for MB at the Hospital for
      Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue
      microarray was constructed from the tumor samples. The arrays were assayed for
      immunohistochemical expression of MYC, p53, platelet-derived growth factor
      receptor-alpha, ErbB2, MIB-1, and TrkC and for apoptosis (terminal
      deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and
      multivariable analyses were conducted to characterize the association between
      survival and both clinical and biological markers. For the strongest predictors
      of survival, a weighted predictive score was calculated based on their hazard
      ratios (HRs). The sum of these scores was then used to give an overall prediction
      of survival using a nomogram. RESULTS: The four strongest predictors of survival
      in the final multivariable model were the presence of metastatic disease at
      presentation (HR, 2.02; P=0.01) and p53 (HR, 2.29; P=0.02), TrkC (HR, 0.65;
      P=0.14), and ErbB2 (HR, 1.51; P=0.21) immunopositivity. A linear prognostic index
      was derived, with coefficients equal to the logarithm of these HRs. The 5-year
      survival rate for patients at the 10th, 50th, and 90th percentiles of the score
      distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy
      and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy.
      CONCLUSIONS: In this study, we demonstrate an approach to combining both clinical
      and biological markers to quantify risk in MB patients. This provides further
      prognostic information than can be obtained when either clinical factors or
      biological markers are studied separately and establishes a framework for
      comparing prognostic markers in future clinical studies.

PMID- 15569994
TI  - Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a
      special reference to activator protein-2, HER2, and prognosis.
AB  - PURPOSE: In the present study, we investigated the expression and prognostic
      value of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer as well as
      their relation to transcription factor activator protein (AP)-2 and HER2
      oncogene. The role of invasion and metastasis-promoting MMPs and their potential
      regulators, AP-2 and HER2, is currently still unclear in breast cancer.
      EXPERIMENTAL DESIGN: MMP-2 and MMP-9 expressions were analyzed
      immunohistochemically in a large prospective series of 421 breast cancer patients
      diagnosed and treated between 1990 and 1995 at Kuopio University Hospital
      (Kuopio, Finland). The relation of MMP-2 and MMP-9 expressions to AP-2, HER2,
      clinicopathological data, and survival was investigated. RESULTS: Both MMP-2 and
      MMP-9 were expressed in the cytoplasm of malignant and stromal cells. High
      expression of MMPs in carcinoma cells was related to small tumors (T1, stage I),
      whereas positive stromal expression of MMPs was associated with aggressive
      factors. High expression of MMP-2 and MMP-9 in carcinoma cells, but not in
      stromal cells, was related to high AP-2 expression. Positive stromal MMP-2
      expression was associated with HER2 overexpression in the whole patient group and
      in the node-negative patient subgroup. Positive stromal MMP-9 expression was
      related to HER2 overexpression in estrogen receptor (ER)-positive disease. In the
      univariate survival analysis, positive stromal MMP-9 predicted shorter recurrence
      free survival (RFS; P=0.0389) and breast cancer-related survival (BCRS; P=0.0081)
      in ER+ disease, especially in the subgroup of ER+ tumors of < or =2 cm in
      diameter (T1; P=0.0031 for RFS, and P=0.0089 for BCRS). High MMP-9 expression in
      cancer cells predicted longer RFS (P=0.0351) in the whole patient group. In the
      multivariate analysis of the whole patient group, the independent predictors of
      shorter RFS were reduced MMP-9 expression in carcinoma cells (P=0.0248), HER2
      overexpression (P=0.0001), and advanced-stage disease (P=0.0002). Shorter BCRS
      was predicted by advanced-stage disease (P <0.0001). CONCLUSIONS: Expression of
      MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2
      and HER2. Positive stromal MMP-9 expression predicts poor survival in the hormone
      responsive small tumors, whereas MMP-9 expression in carcinoma cells favors
      survival. Evaluation of MMP-9 expression seems to add valuable information on
      breast cancer prognosis.

PMID- 15569995
TI  - Granulin-epithelin precursor overexpression promotes growth and invasion of
      hepatocellular carcinoma.
AB  - PURPOSE: Granulin-epithelin precursor (GEP) is a novel growth factor. Our earlier
      cDNA microarray study indicated that GEP was overexpressed in hepatocellular
      carcinoma (HCC). The aim of this study was to investigate the clinical
      significance of GEP expression and its potential as a therapeutic target in HCC.
      EXPERIMENTAL DESIGN: A total of 110 pairs of HCCs and adjacent nontumor liver
      tissues, and 22 normal liver tissues were examined. The GEP RNA level was
      examined by quantitative reverse transcription-PCR, and protein localization by
      immunohistochemistry. The GEP function was examined by transfection experiments.
      RESULTS: The RNA levels of the HCCs were significantly higher than those of the
      nontumor liver tissues and normal livers (P <0.001). GEP protein staining was
      observed in tumor cytoplasm, and the GEP protein levels of the HCCs were also
      significantly higher than those of the nontumor liver tissues and normal livers
      (P <0.001). The majority of HCCs demonstrated up-regulation of GEP protein
      compared with their adjacent liver tissues [79 (71.8%) of 110]. Positive
      correlation of GEP RNA with protein levels was observed in HCCs (P <0.01). Strong
      GEP expression was associated with large HCCs, venous infiltration, and early
      intrahepatic recurrence (P <0.05). Functional studies on the HCC cell line Hep3B
      demonstrated that reduction of GEP protein levels resulted in decreased cell
      proliferation rates, tumor invasion ability, anchorage-independent growth in soft
      agar, and tumorigenicity in nude mice (P <0.05). CONCLUSION: GEP is an important
      factor for HCC growth, invasion, and metastasis. GEP has the potential to serve
      as a tumor marker and therapeutic target.

PMID- 15569996
TI  - HMGA1 protein overexpression in human breast carcinomas: correlation with ErbB2
      expression.
AB  - We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast
      tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular
      atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas,
      and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1
      staining was intense in 40% of hyperplastic lesions with cellular atypia and in
      60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions
      without cellular atypia. Because HMGA1 expression was similar among ductal breast
      carcinomas with different histologic grading, we evaluated the association
      between HMGA1 expression and that of other markers of breast carcinoma invasion
      (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of
      grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We
      found that HMGA1 expression tended to be associated only with c-erbB-2 expression
      (Spearman rho: 0.36; P=0.065). Taken together, these results suggest that HMGA1
      expression might be a novel indicator for the diagnosis and prognosis of human
      breast cancer.

PMID- 15569997
TI  - Inhibition of inhibitor of nuclear factor-kappaB phosphorylation increases the
      efficacy of paclitaxel in in vitro and in vivo ovarian cancer models.
AB  - We investigated whether inhibition of nuclear factor-kappaB (NFkappaB) increases
      the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models.
      Treatment of paclitaxel-sensitive Caov-3 cells with paclitaxel transiently
      activated the phosphorylation of Akt, the phosphorylation of IkappaB kinase
      (IKK), and the phosphorylation of inhibitor of NFkappaB (IkappaBalpha).
      Paclitaxel also caused a transient increase in NFkappaB activity, followed by a
      decrease in NFkappaB activity. We show an association between Akt and IKK and
      show that the phosphorylation of IKK induced by paclitaxel is blocked by
      treatment with a phosphatidylinositol 3-kinase inhibitor (wortmannin or
      LY294002). Furthermore, interference of the Akt signaling cascade inhibits the
      transient induction of IkappaBalpha phosphorylation and NFkappaB activity by
      paclitaxel. Inhibition of NFkappaB activity by treatment with an IkappaBalpha
      phosphorylation inhibitor (BAY 11-7085) attenuated both basal and transient
      induction of IkappaBalpha phosphorylation by paclitaxel. Treatment with BAY 11
      7085 also enhanced the inhibition of NFkappaB activity by paclitaxel for up to 24
      hours. In addition, treatment with BAY 11-7085 decreased the viability of cells
      treated with paclitaxel. Moreover, treatment with BAY 11-7085 increased the
      efficacy of paclitaxel-induced inhibition of intraabdominal dissemination and
      production of ascites in athymic nude mice inoculated intraperitoneally with Caov
      3 cells. These results suggest that paclitaxel transiently induces NFkappaB
      activity via the phosphatidylinositol 3-kinase/Akt cascade and that combination
      therapy with paclitaxel and an NFkappaB inhibitor would increase the therapeutic
      efficacy of paclitaxel.

PMID- 15569998
TI  - The effects of taurolidine, a novel antineoplastic agent, on human malignant
      mesothelioma.
AB  - PURPOSE: Malignant mesothelioma (MM) is a cancer with uniformly poor responses to
      current therapeutic regimens. This study evaluates whether taurolidine, a novel
      antineoplastic agent, is effective against human MM cell lines and a murine model
      of human MM. EXPERIMENTAL DESIGN: Cell growth inhibition and viability assays
      were performed on REN, LRK, and H28 cell lines after 24-72-h exposure to 0-200
      microm taurolidine. Cell cycle analysis with annexin-V binding, terminal
      deoxynucleotidyl transferase-mediated nick end labeling assay, electron
      microscopy, and response to the general caspase inhibitor z-VAD-fmk were
      performed on MM cell lines after 24-72-h exposure to 50-150 microm taurolidine.
      Athymic mice were given i.p. injections of 20 x 10(6) REN cells, followed by i.p.
      taurolidine (17.5 or 20 mg), 3 days/week for up to 3 weeks. Tumors were assessed
      at day 30. All statistical tests were two-sided. RESULTS: A 72-h exposure of MM
      cells to taurolidine showed IC50 of 28-42.7 microm and 50% viability at 49.8-135
      microm. Annexin V assay for apoptosis revealed significant increases in annexin
      binding after 24-72-h exposure to 50-150 microm taurolidine (P <0.05), which was
      significantly inhibited by z-VAD (P <0.05). MM cells exposed to 50-150 microm
      taurolidine for 24-72 h showed terminal deoxynucleotidyl transferase-mediated
      nick end labeling staining consistent with apoptosis, as well as structural
      evidence of apoptosis via electron microscopy. In vivo, there were significant
      tumor reductions (62 to >99% reduction) for all dosage regimens compared with
      untreated controls (P <0.001). In addition, all control animals exhibited ascites
      and diaphragmatic tumors while treated animals did not. CONCLUSIONS: Taurolidine
      has significant antineoplastic activity against MM in vitro and in vivo, in part,
      due to tumor cell apoptosis. These findings warrant further study for potential
      clinical usefulness.

PMID- 15569999
TI  - Antitumor efficacy of oblimersen Bcl-2 antisense oligonucleotide alone and in
      combination with vinorelbine in xenograft models of human non-small cell lung
      cancer.
AB  - Overexpression of Bcl-2 protein in cancer cells can inhibit programmed cell death
      and engender chemoresistance. Reducing Bcl-2 protein levels by using antisense
      oligonucleotides targeting the gene message can increase the sensitivity of
      cancer cells to cytotoxic agents. The objective of this work was to investigate
      the antitumor efficacy of the Bcl-2 antisense oligonucleotide oblimersen
      (Genasense; G3139), alone and in combination with vinorelbine (VNB), in an
      ectopic and orthotopic xenograft model of NCI-H460 human non-small-cell lung
      cancer. In addition to assessing therapeutic effect, Bcl-2 protein expression in
      tumor tissue isolated from lung and heart was measured. In the ectopic xenograft
      model, oblimersen at 5 and 10 mg/kg significantly inhibited tumor growth compared
      with saline-treated control groups, and furthermore, the antitumor effect of
      oblimersen was associated with down-regulation of Bcl-2 protein in isolated tumor
      tissue. Moreover, the combination of oblimersen with VNB was more active in
      inhibiting tumor growth than either drug used alone. In the orthotopic model,
      oblimersen treatment (5 mg/kg) increased the median survival time of mice to 33
      days in comparison with a median survival time of 21 days in the control animals.
      With this model, the anticancer effect was demonstrated by assessing tumor growth
      in lung and heart tissues by hematoxylin and eosin staining and Bcl-2 expression
      by immunohistochemistry. When VNB at 5 mg/kg was combined with oblimersen
      administered at 5 mg/kg, 33% of mice survived more than 90 days. These data
      suggest that the combination of oblimersen and VNB may provide enhanced antitumor
      activities against non-small-cell lung cancer.

PMID- 15570000
TI  - Sensitization of tumor-associated endothelial cell apoptosis by the novel
      vascular-targeting agent ZD6126 in combination with cisplatin.
AB  - PURPOSE: ZD6126 is a novel vascular-targeting agent that selectively disrupts the
      tubulin cytoskeleton of endothelial cells. In the immature vessels characteristic
      of tumor vasculature, this leads to endothelial cell contraction, blood vessel
      congestion, and, consequently, tumor cell death. ZD6126 has been shown to delay
      tumor growth in a range of xenograft models. The antitumor effect of ZD6126 can
      be increased in combination with cisplatin or radiation therapy, although the
      precise mechanism of this enhancement has not been demonstrated. ZD6126 treatment
      has also been shown to inhibit lung metastasis, and the present study has
      explored the potential to increase the antimetastatic effect of ZD6126 by
      combining with cisplatin, and the underlining mechanism has been investigated.
      EXPERIMENTAL DESIGN: Human lung adenocarcinoma PC14PE6 cells were injected into
      the tail vein of nude mice. Five weeks after injection animals were treated with
      ZD6126 (200 mg/kg i.p.), cisplatin (6 mg/kg i.v.), or a combination of the two
      agents. The animals were sacrificed 24 hours later, and the extent of lung
      metastases and the presence of apoptotic cells were assessed. RESULTS: Histologic
      analysis revealed that the ZD6126/cisplatin combination resulted in a 2 to 4-fold
      increase in the total number of tumor-associated apoptotic cells compared with
      either treatment alone. ZD6126 alone induced apoptosis of tumor-associated
      endothelial cells in tumors, and the extent of apoptosis was increased 2-fold in
      combination with cisplatin. The lung weight was significantly reduced, and the
      number of metastatic nodules significantly was lower in the combined treatment
      group than in the control group. CONCLUSIONS: These data suggest that the
      antimetastatic effect of the vascular-targeting agent ZD6126 can be increased by
      use in combination with cisplatin, which increases the incidence of endothelial
      cell apoptosis.

PMID- 15570001
TI  - Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy.
AB  - PURPOSE: The present report describes the development of paclitaxel-loaded
      gelatin nanoparticles for use in intravesical therapy of superficial bladder
      cancer. The commercial formulation of paclitaxel contains Cremophor, which forms
      micelles and thereby entraps the drug and reduces its partition across the
      urothelium. EXPERIMENTAL DESIGN: Paclitaxel-loaded gelatin nanoparticles were
      prepared using the desolvation method, and their physicochemical and biological
      properties were characterized. RESULTS: The size of the particles ranged from 600
      to 1,000 nm and increased with the molecular weight of the gelatin polymer. Under
      optimal conditions, the yield was >80%, and the drug loading was 0.7%. Wide-angle
      X-ray diffraction analysis showed that the entrapped paclitaxel was present in an
      amorphous state, which has higher water solubility compared with the crystalline
      state. Identical, rapid drug release from nanoparticles was observed in PBS and
      urine, with approximately 90% released at 37 degrees C after 2 hours. Treatment
      with a protease (i.e., Pronase) rapidly degraded the nanoparticles, with half
      lives of 23.8 minutes, 0.6 minute, and 0.4 minute in the presence of 0.01, 0.05,
      and 0.25 mg/mL Pronase, respectively. The paclitaxel-loaded nanoparticles were
      active against human RT4 bladder transitional cancer cells; the IC50 paclitaxel
      equivalent concentrations were nearly identical to those of aqueous solutions of
      paclitaxel, i.e., approximately 30 nmol/L (equivalent to approximately 25 ng/mL)
      for 2-hour treatments and approximately 4 nmol/L for 96-hour treatments. In dogs
      given an intravesical dose of paclitaxel-loaded particles, the drug
      concentrations in the urothelium and lamina propria tissue layers, where Ta and
      T1 tumors would be located, were 7.4 +/- 4.3 mug/g (mean +/- SD; 3 dogs; 9 tissue
      sections), which were 2.6x the concentrations we reported for dogs treated with
      the Cremophor formulation. CONCLUSIONS: Paclitaxel-loaded gelatin nanoparticles
      represent a rapid release, biologically active paclitaxel formulation that can be
      used for intravesical bladder cancer therapy.

PMID- 15570002
TI  - Inhibition of metastatic tumor growth in mouse lung by repeated administration of
      polyethylene glycol-conjugated catalase: quantitative analysis with firefly
      luciferase-expressing melanoma cells.
AB  - PURPOSE: To develop a novel and effective approach to inhibit tumor metastasis
      based on controlled delivery of catalase, we first evaluated the characteristics
      of the disposition and proliferation of tumor cells. Then, we examined the
      effects of polyethylene glycol-conjugated catalase (PEG-catalase) on tumor
      metastasis. On the basis of the results obtained, PEG-catalase was repetitively
      administered to completely suppress the growth of tumor cells. EXPERIMENTAL
      DESIGN: Murine melanoma B16-BL6 cells were stably transfected with firefly
      luciferase gene to obtain B16-BL6/Luc cells. These cells were injected
      intravenously into syngeneic C57BL/6 mice. PEG-catalase was injected
      intravenously, and the effect was evaluated by measuring the luciferase activity
      as the indicator of the number of tumor cells. RESULTS: At 1 hour after injection
      of B16-BL6/Luc cells, 60 to 90% of the injected cells were recovered in the lung.
      The numbers decreased to 2 to 4% at 24 hours, then increased. An injection of PEG
      catalase just before inoculation significantly reduced the number of tumor cells
      at 24 hours. Injection of PEG-catalase at 1 or 3 days after inoculation was also
      effective in reducing the cell numbers. Daily dosing of PEG-catalase greatly
      inhibited the proliferation and the number assayed at 14 days after inoculation
      was not significantly different from the minimal number observed at 1 day,
      suggesting that the growth had been markedly suppressed by the treatment.
      CONCLUSIONS: These findings indicate that sustained catalase activity in the
      blood circulation can prevent the multiple processes of tumor metastasis in the
      lung, which could lead to a state of tumor dormancy.

PMID- 15570003
TI  - Species differences in troxacitabine pharmacokinetics and pharmacodynamics:
      implications for clinical development.
AB  - PURPOSE: Troxacitabine is the first unnatural L-nucleoside analog to show potent
      preclinical antitumor activity and is currently under clinical investigation.
      Significant differences in troxacitabine toxicity between mice, rats, monkeys,
      and humans were observed during preclinical and clinical evaluations. To better
      understand the different toxicity and efficacy results observed between the human
      xenograft mouse tumor models used for preclinical assessment and the clinical
      study results, the pharmacodynamics and pharmacokinetics of troxacitabine were
      reassessed in murine and human models. EXPERIMENTAL DESIGN: Clonal and thymidine
      incorporation assays were used to investigate the in vitro antiproliferative
      activity of troxacitabine on a selected panel of mouse and human tumor cell lines
      and normal hemapoietic cells. Analysis of the intracellular metabolites of
      [14C]troxacitabine was determined in mouse and human T-lymphocytes obtained from
      peripheral blood. The antitumor efficacy of troxacitabine administered either as
      single or repeated high-dose bolus administrations or as low-dose continuous
      infusions was evaluated in the human colon HT-29 xenograft model. We also
      determined plasma concentrations of troxacitabine using the different
      administration schedules. RESULTS: Five to nine hundred-fold lower concentrations
      of troxacitabine were required to inhibit cell growth in human compared with
      murine tumor and normal hemapoietic cell lines. Furthermore, the sensitivity of
      cells of both species to troxacitabine was strongly time dependent, requiring >24
      hours exposure for maximum activity. Analysis of the intracellular metabolites of
      [14C]troxacitabine in T-lymphocytes obtained from peripheral blood revealed
      subsequently higher levels of mono-, di-, and triphosphates in human compared
      with mouse. Antitumor efficacy studies revealed that prolonged exposure schedules
      (up to 6 days) showed equivalent efficacy to repeated high-dose bolus
      administrations. Five-day continuous infusion of 20 mg/mL troxacitabine via
      subcutaneous implanted mini-osmotic pump maintained systemic concentrations of
      262 ng/mL (1.2 micromol/L) for the duration of administration, which are
      clinically achievable plasma concentrations, and led to significant antitumor
      activity [treated versus control (T/C) of 27% and tumor regression during
      treatment]. CONCLUSIONS: These studies support the hypothesis that troxacitabine
      infusions might be the administration regimen with the greatest likelihood of
      fully exploiting clinically the potent preclinical antitumor activity of
      troxacitabine.

PMID- 15570004
TI  - Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of
      estrogen-dependent human breast cancer (mcf-7) in nude mice.
AB  - PURPOSE: This study determined the effect of 10% dietary flaxseed (FS) and
      tamoxifen (TAM), alone and in combination, on the growth of estrogen-dependent
      human breast cancer (MCF-7) in athymic mice with or without 17beta-estradiol (E2)
      supplementation. EXPERIMENTAL DESIGN: Ovariectomized mice received injection with
      MCF-7 cells, were implanted with an E2 pellet (1.7 mg), and fed the basal diet
      (BD). When tumor reached approximately 40 mm2, the E2 implant was removed, and
      mice were randomized to the following groups and maintained at either low (E2
      pellet removed) or high E2 level (new E2 pellet implanted) for 6 weeks: (a)
      positive control with new E2 pellet, fed BD, (b) negative control with no E2
      implant, fed BD, (c) TAM group with TAM pellet (5 mg) implant, fed BD, (d) FS
      group fed 10% FS, (e) FS+TAM group with TAM implant, fed 10% FS. Tumor growth was
      monitored weekly. RESULTS: At low E2 level, FS regressed the pretreatment tumor
      size by 74%. TAM regressed tumor initially but later induced an increase so that
      the tumor size was finally similar to the pretreatment size. A tumor regression
      >53% was induced by FS+TAM than by TAM alone. At high E2 level, FS, TAM, and
      FS+TAM inhibited the tumor growth by 22, 41, and 50%, respectively, compared with
      the positive control. Decreased tumor size was attributable to reduced tumor cell
      proliferation and increased apoptosis. CONCLUSIONS: FS inhibited the growth of
      human estrogen-dependent breast cancer and strengthened the tumor-inhibitory
      effect of TAM at both low and high E2 levels.

PMID- 15570005
TI  - Application of a macromolecular contrast agent for detection of alterations of
      tumor vessel permeability induced by radiation.
AB  - Permeability of tumor vasculature can be a major barrier to successful drug
      delivery, particularly for high molecular weight agents such as monoclonal
      antibodies and their diagnostic or therapeutic conjugates. In this study, changes
      in permeability of SCCVII tumor vessels after radiation treatment were evaluated
      by dynamic magnetic resonance imaging as a function of time after irradiation
      using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance
      imaging contrast agent shown previously to be confined to tumor blood vessels.
      Tumor irradiation consisted of either single doses (2-15 Gy) or various daily
      fractionated doses (5 days). A single radiation dose of 15 Gy resulted in
      significant transient image enhancement of the tumor tissue with a maximum
      occurring between 7 and 24 hours after radiation treatment. No observable
      enhancement was recorded for fractionated radiation doses. Use of dynamic
      magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology
      capable of defining the timing of enhanced permeability of macromolecules in
      tumors after irradiation. Such information might be applied to optimize the
      efficacy of subsequent or concurrent therapies including radiolabeled antibodies
      or other anticancer agents in combination with external beam therapies.

PMID- 15570006
TI  - Antitumor activity of small interfering RNA/cationic liposome complex in mouse
      models of cancer.
AB  - PURPOSE: The RNA interference effect is an alternative to antisense DNA as an
      experimental method of down-regulating a specific target protein. Although the
      RNA interference effect, which is mediated by small interfering RNA (siRNA) or
      micro-RNA, has potential application to human therapy, the hydrodynamic method
      usually used for rapid administration of oligonucleotides is unsuitable for use
      in humans. In this study, we have investigated the antitumor activity of a
      synthetic siRNA, B717, which is sequence specific for the human bcl-2 oncogene,
      complexed with a novel cationic liposome, LIC-101. EXPERIMENTAL DESIGN: In a
      mouse model of liver metastasis, we administered B717/LIC-101 by bolus
      intravenous injection, adjusting the rate and volume of administration to what is
      feasible in human therapy. In a mouse model bearing prostate cancer in which the
      cells were inoculated under the skin, B717/LIC-101 was administered
      subcutaneously around the tumor. RESULTS: The B717/LIC-101 complex inhibited the
      expression of bcl-2 protein and the growth of tumor cell lines in vitro in a
      sequence-specific manner in the concentration range of 3 to 100 nmol/L.
      Furthermore, the complex had a strong antitumor activity when administered
      intravenously in the mouse model of liver metastasis. B717 (siRNA) was shown to
      be delivered to tumor cells in the mouse liver, but only when complexed with LIC
      101. The complex also inhibited tumor cell growth in the mouse model bearing
      prostate cancer. CONCLUSIONS: By combining siRNA with our cationic liposome, we
      overcame the difficulty of administering siRNA to animals in ways that can be
      applied in human therapy. Although our siRNA/liposome complex is not yet in
      clinical trials, it is expected to provide a novel siRNA therapy for cancer
      patients.

PMID- 15570007
TI  - Regression of mouse prostatic intraepithelial neoplasia by nonsteroidal anti
      inflammatory drugs in the transgenic adenocarcinoma mouse prostate model.
AB  - PURPOSE: Epidemiologic studies have revealed a decreased risk of colon cancer
      among people who have regularly taken cyclooxygenase (COX)-2 inhibitors such as
      aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas the
      selective COX-2 inhibitor celecoxib and exisulind, a metabolic product of
      sulindac, have gained increasing attention as efficacious chemopreventive agents
      against colon and prostate cancer, not much is known about the underlying
      molecular targets and mechanisms. Moreover, the side effects of NSAIDs are a
      major obstacle for large-scale application to the prevention of cancer in humans;
      for example, in the United States in 1998, there were 16,550 deaths from NSAID
      induced gastrointestinal complications. The toxicity associated with these
      compounds is raising concerns, and more needs to be known about their mode of
      action and molecular targets. EXPERIMENTAL DESIGN: We used the transgenic mouse
      prostate (TRAMP) model, which exhibits similarities with human prostate cancer,
      including epithelial origin, progression from the PIN stage to adenocarcinoma,
      and metastasis by a transgene that is hormonally regulated by androgens. In
      addition to histologically analyzing the PIN lesions of the dorsolateral prostate
      from TRAMP mice, we delineated the molecular targets and mechanisms of celecoxib
      and exisulind against mouse PIN lesions. We performed Western blot analysis of
      the total protein lysate from the tissues of mouse PIN lesions to measure the
      level of expression of androgen receptor, vascular endothelial growth factor,
      nuclear factor-kappaB p65, BclII, AKT (total and phosphorylated Ser473), p53,
      cyclin-dependent kinase inhibitor p21WAF1/CIP1, p27, BAX, and caspase-3 to
      demonstrate the COX-2-independent mechanism involved in the inhibition of PIN
      lesions of the dorsolateral prostate by both celecoxib and exisulind. RESULTS: We
      found for the first time that (a) both celecoxib and exisulind as dietary
      supplements induce strong inhibitory effects against prostate cancer at doses of
      800 and 500 ppm, respectively, after 16 weeks; (b) the histologic analysis of the
      dorsolateral prostate after 2 weeks of treatment indicated a reduction of PIN
      lesions from 75% to 19% with celecoxib and to 16% with exisulind; (c) more
      importantly, those few PINs and adenocarcinomas in the groups treated with
      celecoxib or exisulind showed more apoptotic cells, lower levels of proliferating
      cell nuclear antigen, and a lower number of mitotic cells. To understand the
      molecular mechanisms involved in the inhibition of PIN lesions, first, we
      examined the expression of molecular targets involved in angiogenesis and
      inflammatory processes. It was clearly evident from Western blot analysis of the
      total protein lysate derived from the dorsolateral prostate tissues with PIN
      lesions that expression of androgen receptor, vascular endothelial growth factor,
      nuclear factor-kappaB p65, and BclII is down-regulated more effectively by
      celecoxib. Down-regulation of AKT protein (total and phosphorylated at Ser473)
      signaling by celecoxib clearly indicates an inhibition of the survival gene and
      the pathological process that could otherwise lead to adenocarcinoma.
      CONCLUSIONS: Overall, the findings from this study clearly show the effectiveness
      of celecoxib and exisulind in reducing the PIN lesions by modulating a cascade of
      molecular targets involved in COX-2-dependent and -independent mechanisms.
      Whereas these agents are already in clinical trial or in use as chemopreventive
      agents, findings from this study demonstrate the difference in their mode of
      action, thus helping us to understand the side effects.

PMID- 15570008
TI  - Vector targeting makes 5-fluorouracil chemotherapy less toxic and more effective
      in animal models of epithelial neoplasms.
AB  - PURPOSE: 5-fluorouracil (5-FU) has been combined in the past with other drugs for
      the combination chemotherapy for cancers of the breast, ovary, and colon. These
      drug regimens were limited by the fact that 5-FU fails to kill nondividing cancer
      cells at the doses that are safe to deliver. The goal of the present study is to
      test the feasibility of replacing 5-FU in established 5-FU combination
      chemotherapy with the Ad-LpCDIRESE1A/5-fluorocytosine (5-FC) system for the
      purpose of reducing toxicity and increasing efficacy. EXPERIMENTAL DESIGN: We
      have replaced 5-FU in the weekly combination of CPT-11, folinic acid (FA) and 5
      FU chemotherapy by 5-FC and an adenoviral vector that carries the L-plastin (Lp)
      tumor-specific promoter-driven transcription unit encoding the cytosine deaminase
      gene linked to the E1A gene by an internal ribosomal entry site element. This
      combination is called "genetic combination therapy." The goal of using the vector
      was to decrease the toxicity to normal tissue and to increase the efficacy of
      therapy in the cancer cells by increasing the concentration of 5-FU sufficiently
      high that even nondividing cancer cells would be killed by 5-FU through its
      incorporation into mRNA and consequent inhibition of synthesis of functional
      proteins. We compared the in vivo efficacy of the genetic combination therapy
      with the conventional combination chemotherapy in a mouse colon cancer model.
      RESULTS: Both replication-competent and -noncompetent adenoviral vectors carrying
      an L-plastin-driven cytosine deaminase transcription unit when combined with 5
      FC, CPT-11, and FA showed increased in vitro therapeutic activity that was
      significantly higher than that of the conventional chemotherapy combination.
      Tumor-bearing mice treated with the genetic combination therapy showed a
      statistically significant advantage in terms of increased response rate, response
      duration, survival, and reduced toxicity when compared with tumor-bearing mice
      treated with the conventional combination chemotherapy. CONCLUSIONS: Replacement
      of 5-FU in 5-FU-based combination chemotherapy with the Ad-LpCDIRESE1A vector and
      5-FU reduces toxicity and increases efficacy. This is a concept that could be
      potentially applied widely for many forms of cancer treatment.

PMID- 15570009
TI  - Trastuzumab down-regulates Bcl-2 expression and potentiates apoptosis induction
      by Bcl-2/Bcl-XL bispecific antisense oligonucleotides in HER-2 gene--amplified
      breast cancer cells.
AB  - PURPOSE: To investigate the possible existence of an antiapoptotic cross-talk
      between HER-2 and antiapoptotic Bcl-2 family members. EXPERIMENTAL DESIGN: Bcl-2
      and Bcl-XL expression and apoptosis induction were analyzed in HER-2 gene
      amplified (BT474) and nonamplified (ZR 75-1) breast cancer cell lines exposed to
      trastuzumab, alone or in combination with either Bcl-2/Bcl-XL bispecific
      antisense oligonucleotides (AS-4625) or the small-molecule Bcl-2 antagonist HA14
      1. RESULTS: In addition to HER-2 and epidermal growth factor receptor,
      trastuzumab down-regulated Bcl-2, but not Bcl-XL, protein, and mRNA expression in
      BT474 cells. Interestingly, trastuzumab-induced down-regulation of HER-2 and Bcl
      2 was also observed in three of five and two of three breast cancer patients
      undergoing trastuzumab treatment, respectively. Despite Bcl-2 down-regulation,
      however, trastuzumab only marginally increased the rate of apoptosis (7.3 +/-
      3.5%). We therefore investigated whether a combination of AS-4625 and trastuzumab
      might increase proapoptotic efficiency. AS-4625 treatment of BT474 cells
      decreased both Bcl-2 and Bcl-XL expression, resulting in a 21 +/- 7% net
      apoptosis induction; the combination of AS-4625 followed by trastuzumab resulted
      in a significantly stronger induction of apoptosis (37 +/- 6%, P <0.01) that was
      not observed with the reverse treatment sequence (trastuzumab followed by AS
      4625). Similar results were obtained with the Bcl-2 antagonist HA14-1; indeed,
      exposure of BT474 cells to HA14-1 followed by trastuzumab resulted in a striking
      proapoptotic synergism (combination index=0.58 +/- 0.18), as assessed by
      isobologram analysis. CONCLUSIONS: Altogether our findings suggest that combined
      targeting of HER-2 and Bcl-2 may represent a novel, rational approach to more
      effective breast cancer therapy.

PMID- 15570010
TI  - In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell
      carcinoma cells.
AB  - PURPOSE: Bcl-xL overexpression is common in head and neck squamous cell
      carcinomas (HNSCC) and correlates with resistance to chemotherapy. Thus, a
      nonpeptidic, cell-permeable small molecule that mimics the BH3 domain of
      proapoptotic proteins may inhibit Bcl-xL function and have therapeutic potential
      for HNSCC by overcoming drug-resistance. (-)-Gossypol, the levorotatory isomer of
      a natural product isolated from cottonseeds and roots, was recently discovered to
      bind to the BH3 binding groove of Bcl-xL and Bcl-2. EXPERIMENTAL DESIGN: We
      investigated the in vitro effects of (-)-gossypol on HNSCC cell lines as well as
      on fibroblast and keratinocyte cultures by using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) cell survival assays and assessed the results
      with respect to Bcl-2 family protein expression. RESULTS: We observed dose
      dependent growth inhibition of 10 HNSCC cell lines at biologically achievable
      doses (2.5-10 micromol/L). (-)-Gossypol doses required to inhibit the growth of
      human fibroblast cell lines by 50% were 2- to 10-fold higher than for HNSCC cell
      lines. To inhibit human oral keratinocyte growth by 50%, (-)-gossypol
      concentrations were 2-to 3-fold higher than for HNSCC cell lines. CONCLUSIONS:
      There is a direct correlation between Bcl-xL-to-Bcl-xS ratios and sensitivity to
      (-)-gossypol. This agent induced apoptosis in a much higher proportion of cells
      with wild-type p53. Importantly, cell lines resistant to cisplatin were very
      sensitive to (-)-gossypol. These results demonstrate that (-)-gossypol has potent
      antitumor activity in HNSCC in vitro. This agent may be developed as a novel
      therapeutic agent for HNSCC, either alone or in combination with existing
      chemotherapeutic agents.

PMID- 15570011
TI  - Deregulated cyclin D1 expression is associated with decreased efficacy of the
      selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in
      head and neck squamous cell carcinoma cell lines.
AB  - PURPOSE: Despite promising initial results, recent Phase III trials of the
      selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      gefitinib ("Iressa"; AstraZeneca, Wilmington, Delaware) in advanced head and neck
      squamous cell carcinoma (HNSCC) have been equivocal. Cyclin D1, an EGFR target
      gene, is frequently overexpressed in HNSCC, has been implicated in its
      pathogenesis, and is strongly associated with poor prognosis in this disease.
      Therefore, we examined the relationship between deregulated cyclin D1 expression
      and sensitivity to gefitinib to determine whether this frequently occurring
      oncogenic change affected the cellular response to gefitinib. EXPERIMENTAL
      DESIGN: A panel of six EGFR-overexpressing HNSCC cell lines was used to correlate
      CCND1 gene copy number, cyclin D1 expression, and response to gefitinib. The
      effect of constitutive overexpression of cyclin D1 was assessed by establishing
      stably transfected clonal SCC-9 cell lines. RESULTS: Three of six cell lines
      displayed cyclin D1 amplification and/or overexpression, and these cell lines
      were resistant to gefitinib. SCC 9 clones overexpressing cyclin D1 continued to
      proliferate and maintained their S-phase fraction when treated with gefitinib,
      whereas empty vector control clones and the parental SCC 9 cells were profoundly
      inhibited and displayed marked reductions in S-phase. The resistance of cyclin D1
      overexpressing clones and cyclin D1-amplified cell lines was associated with
      maintenance of cyclin D1 expression after gefitinib treatment. CONCLUSIONS: These
      data suggest that deregulated cyclin D1 overexpression may be associated with
      resistance of HNSCC to EGFR inhibitors. Therefore, the role of cyclin D1 as a
      marker of therapeutic response and its utility as a prognostic marker in HNSCC
      warrant additional analysis.

PMID- 15570012
TI  - Autocrine motility factor signaling enhances pancreatic cancer metastasis.
AB  - PURPOSE: Autocrine motility factor (AMF)/phosphoglucose isomerase (PGI) is a
      ubiquitous cytosolic enzyme that plays a key role in glycolysis. AMF/PGI is also
      a multifunctional protein that acts in the extracellular milieu as a potent
      mitogen/cytokine. Increased expression of AMF/PGI and its receptor has been found
      in a wide spectrum of malignancies and is associated with cancer progression and
      metastasis. Recent studies indicated that AMF is induced by hypoxia and enhances
      the random motility of pancreatic cancer cells. In the present study, the role
      and regulation of AMF in the growth and metastasis of pancreatic cancer cells
      were determined. EXPERIMENTAL DESIGN: In this study, we assessed whether
      overexpression of AMF in human pancreatic cancer cells enhances the liver
      metastasis using an orthotopic mouse tumor model. We also investigated the
      intracellular signal transduction pathways of AMF in human pancreatic cancer cell
      lines. RESULTS: Overexpression of AMF stimulated in vitro invasion of MIA PaCa-2
      cells. In vivo, after orthotopic implantation into the pancreas of nude mice,
      parental and empty vector-transfected MIA PaCa-2 cells produced locally
      relatively small tumors with no evidence of liver metastasis, whereas AMF
      transfected MIA PaCa-2 cells produced the large tumors and liver metastases. In
      addition, over-expression of AMF leads to down-regulation of E-cadherin
      expression associated with the up-regulation of the zinc-finger transcription
      factor SNAIL expression. CONCLUSIONS: The data submitted here show that AMF
      expression significantly contributes to the aggressive phenotype of human
      pancreatic cancer and thus may provide a novel prognostic and therapeutic target.

PMID- 15570013
TI  - MIB-1 and p27Kip1 expression in nephroblastoma.

PMID- 15570014
TI  - Rapid, membrane-initiated actions of 1,25 dihydroxyvitamin D: what are they and
      what do they mean?
AB  - Vitamin D is a conditionally required nutrient traditionally thought to influence
      physiology as the metabolite 1,25-dihydroxyvitamin D [1,25(OH)(2) D] by binding
      to the vitamin D receptor (VDR) and stimulating the transcription of genes
      through direct VDR-DNA interactions. However, over the past 15 y research has
      demonstrated that 1,25(OH)(2) D, as well as other steroid hormones, can rapidly
      stimulate ion fluxes and activate protein kinases by transcription-independent
      mechanisms. This review summarizes recent research on the rapid actions of
      1,25(OH)(2) D and identifies questions that remain to be answered in this area.

PMID- 15570015
TI  - Molecular mechanisms of the chemopreventive effects of resveratrol and its
      analogs in colorectal cancer: key role of polyamines?
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape
      skins, peanuts, and red wine, has been reported to exhibit a wide range of
      biological and pharmacological properties. It has been speculated that dietary
      resveratrol may act as an antioxidant, promote nitric oxide production, inhibit
      platelet aggregation, and increase high-density lipoprotein cholesterol and
      thereby serve as a cardioprotective agent (the so-called "French paradox").
      Recently, it was demonstrated that resveratrol can function as a cancer
      chemopreventive agent, and there has been a great deal of experimental effort
      directed toward defining this effect. It has been shown that resveratrol and some
      of its analogues interfere with signal transduction pathways. Thus the activities
      of various protein kinases are inhibited, the expression of nuclear proto
      oncogenes declines, and the activity of ornithine decarboxylase (ODC) is reduced.
      ODC, which catalyzes the rate-limiting step in the biosynthesis of polyamines, is
      closely linked with cellular proliferation and carcinogenesis. This review
      summarizes the recent advances that have provided new insights into the molecular
      mechanisms underlying the promising properties of resveratrol focusing on the key
      role of the polyamine metabolism in colorectal cancer cells.

PMID- 15570016
TI  - Quantitative determination of rumen ciliate protozoal biomass with real-time PCR.

PMID- 15570017
TI  - Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and
      stress signaling in human lens epithelial cells.
AB  - Epidemiological studies suggest that consumption of vegetables rich in the
      xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing
      age-related cataract, a leading cause of vision loss. Although LUT and ZEA are
      the only dietary carotenoids present in the lens, direct evidence for their
      photoprotective effect in this organ is not available. The present study examined
      the effects of xanthophylls and alpha-tocopherol (alpha-TC) on lipid peroxidation
      and the mitogen-activated stress signaling pathways in human lens epithelial
      (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with
      LUT, ZEA, astaxanthin (AST), and alpha-TC as methyl-beta-cyclodextrin complexes,
      HLE cells accumulated the lipophiles in a concentration- and time-dependent
      manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures
      with either 2 micromol/L xanthophyll or 10 micromol/L alpha-TC for 4 h before
      exposure to 300 J/m(2) UVB radiation decreased lipid peroxidation by 47-57%
      compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls
      and alpha-TC also inhibited UVB-induced activation of c-JUN NH(2)-terminal kinase
      (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition
      of UVB-induced JNK and p38 activation for cells containing <0.20 and
      approximately 0.30 nmol xanthophylls/mg, respectively, whereas >2.3 nmol alpha
      TC/mg protein was required to significantly decrease UVB-induced stress
      signaling. These data suggest that xanthophylls are more potent than alpha-TC for
      protecting human lens epithelial cells against UVB insult.

PMID- 15570018
TI  - An increase in reactive oxygen species by dietary fish oil coupled with the
      attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte
      apoptosis.
AB  - We showed previously that the dietary combination of fish oil, rich in (n-3)
      fatty acids, and the fermentable fiber pectin enhances colonocyte apoptosis in a
      rat model of experimentally induced colon cancer. In this study, we propose that
      the mechanism by which this dietary combination heightens apoptosis is via
      modulation of the colonocyte redox environment. Male Sprague-Dawley rats (n = 60)
      were fed 1 of 2 fats (corn oil or fish oil) and 1 of 2 fibers (cellulose or
      pectin) for 2 wk before determination of reactive oxygen species (ROS), oxidative
      DNA damage, antioxidant enzyme activity [superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx)] and apoptosis in isolated colonocytes. Fish
      oil enhanced ROS, whereas the combination of fish oil and pectin suppressed SOD
      and CAT and enhanced the SOD/CAT ratio compared with a corn oil and cellulose
      diet. Despite this modulation to a seemingly prooxidant environment, oxidative
      DNA damage was inversely related to ROS in the fish oil and pectin diet, and
      apoptosis was enhanced relative to other diets. Furthermore, apoptosis increased
      exponentially as ROS increased. These results suggest that the enhancement of
      apoptosis associated with fish oil and pectin feeding may be due to a modulation
      of the redox environment that promotes ROS-mediated apoptosis.

PMID- 15570019
TI  - Dietary fatty acids regulate acyl-CoA:cholesterol acyltransferase and cytosolic
      cholesteryl ester hydrolase in hamsters.
AB  - To investigate the effects of dietary fatty acids on acyl-CoA:cholesterol
      acyltransferase (ACAT) and cytosolic cholesteryl ester hydrolase (cCEH), male
      Syrian hamsters (F(1)B hybrid) were fed a modified version of the NIH-07 open
      formula, cereal-based rodent diet enriched with one of the following 4 dietary
      fatty acids: palmitic acid (16:0), trans fatty acids (18:1t), oleic acid (18:1c),
      or linoleic acid (18:2). Hamsters fed 16:0 and 18:1t had significantly higher
      plasma non-HDL cholesterol concentrations compared with those fed 18:1c and 18:2.
      However, differences in plasma apolipoprotein (apo)B(100) concentration, hepatic
      cCEH mRNA abundance, and hepatic ACAT activity between 16:0- and 18:1t-fed
      hamsters suggest that the hypercholesterolemic effects are achieved by different
      mechanisms. Specifically, an increase in ACAT activity by 16:0 may induce
      enrichment of cholesteryl esters in apoB(100)-containing particles, whereas 18:1t
      may increase the number of the particles. Hepatic cholesteryl esters accumulated
      in the 18:1c- and 18:2-fed groups with no differences in hepatic ACAT activity
      and cCEH mRNA abundance among hamsters fed unsaturated fatty acids (i.e., 18:1t,
      18:1c, and 18:2). Considering the lack of change in free cholesterol
      concentration and increased cholesteryl esters in the liver, the
      hypocholesterolemic effect of 18:1c and 18:2 compared with 18:1t may be
      attributed to decreased production of apoB(100)-containing particles. ACAT-1 was
      expressed in all the tissues examined; in contrast, ACAT-2 was highly expressed
      in the liver and small intestine. Hepatic ACAT activity was disproportionate to
      the levels of ACAT-1 and ACAT-2 mRNA and protein, indicating post-transcriptional
      regulation of ACAT by dietary fatty acids. The data suggest that cholesterolemic
      effects of individual dietary fatty acids can be achieved through their
      independent modulation of pathways regulating assembly and secretion of apoB(100)
      containing particles.

PMID- 15570020
TI  - Five cysteine-containing compounds delay diabetic deterioration in Balb/cA mice.
AB  - The effects of n-acetyl cysteine (NAC), s-allyl cysteine (SAC), s-ethyl cysteine,
      s-methyl cysteine and s-propyl cysteine (SPC) activity on Balb/cA mice against
      diabetic complications were examined. These complications included hyperglycemia,
      hyperlipidemia, oxidation stress, blood coagulation, and cytokine imbalance. To
      induce diabetes, mice were treated with streptozotocin i.p. for 5 consecutive
      days. Five cysteine-containing compounds at 1 g/L were added to the drinking
      water. After intake of the 5 cysteine-containing agents for 4 wk, body weight
      loss, plasma concentrations of glucose and insulin, and fibronectin levels were
      improved (P < 0.05) in diabetic mice. The administration of these agents restored
      the glutathione level (P < 0.05), reduced the loss of catalase and glutathione
      peroxidase activities in kidney and liver (P < 0.05), and decreased glucose
      induced lipid oxidation, as assessed by malondialdehyde formation (P < 0.05). In
      all diabetic mice, the intake of these agents reduced triglyceride levels in
      plasma and liver (P < 0.05); however, only NAC, SAC and SPC treatments reduced
      cholesterol level in liver (P < 0.05). These cysteine-containing agents elevated
      the activity of 2 fibrinolytic factors, protein C and antithrombin III (P <
      0.05). The overexpression of interleukin-6 and tumor necrosis factor-alpha in
      diabetic mice was suppressed by the intake of the 5 cysteine-containing agents (P
      < 0.05). Via their antioxidant activities, the 5 compounds effectively improved
      glycemic control, delayed oxidation damage, downregulated inflammatory cytokines,
      and enhanced anticoagulant activity in diabetic mice. These data support the
      multiple roles of these agents as potential protective agents for delaying
      diabetic deterioration.

PMID- 15570021
TI  - Dietary flaxseed protects against ventricular fibrillation induced by ischemia
      reperfusion in normal and hypercholesterolemic Rabbits.
AB  - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the (n-3) PUFA found
      in fish oils, exert antiarrhythmic effects during ischemia. Flaxseed is the
      richest plant source of another (n-3) PUFA, alpha-linolenic acid (ALA), yet its
      effects remain largely unknown. Our objective was to determine whether a flaxseed
      rich diet is antiarrhythmic in normal and hypercholesterolemic rabbits. Male New
      Zealand White (NZW) rabbits (n = 14-16) were fed as follows: regular diet (REG
      group); diet containing 10% flaxseed (FLX group); 0.5% cholesterol (CHL group);
      or 0.5% cholesterol + 10% flaxseed (CHL/FLX group) for up to 16 wk. Plasma
      cholesterol was significantly elevated in the CHL and CHL/FLX groups. Plasma
      triglycerides were unchanged. ALA levels increased significantly in plasma and
      hearts of the FLX and CHL/FLX groups. After the feeding period, rabbit hearts
      were isolated and subjected to global ischemia (30 min) and reperfusion (45 min).
      Ventricular fibrillation (VF) occurred during ischemia in 33% of REG but in none
      of FLX hearts, and 28% of CHL but only 6% of CHL/FLX hearts. VF incidence during
      reperfusion was 28% and 26% in REG and FLX hearts, respectively. The incidence
      significantly increased to 64% in CHL hearts, and was significantly attenuated
      (18%) in CHL/FLX hearts. CHL markedly prolonged the QT interval, whereas FLX
      significantly shortened the QT interval and reduced arrhythmias in the FLX and
      CHL/FLX hearts. In vitro application of (n-3) PUFA shortened the action potential
      duration, an effect consistent with the QT data. This study demonstrates that
      dietary flaxseed exerts antiarrhythmic effects during ischemia-reperfusion in
      rabbit hearts, possibly through shortening of the action potential.

PMID- 15570022
TI  - Soluble fibroin enhances insulin sensitivity and glucose metabolism in 3T3-L1
      adipocytes.
AB  - Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features
      of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin
      reverses these pathological attributes. To explore the mechanism underlying this
      effect, we used the murine, 3T3-L1 adipocyte cell line, which has been used
      extensively to model adipocyte function. Chronic exposure of 3T3-L1 adipocytes to
      insulin leads to a 50% loss of insulin-stimulated glucose uptake. Chronic
      exposure to different preparations of fibroin partially blocked the response to
      insulin but also increased the sensitivity of control cells to the acute action
      of insulin. The latter effect was most robust at physiologic concentrations of
      insulin. Fibroin did not prevent the insulin-induced downregulation of the
      insulin receptor or the tyrosine kinase activity associated with the receptor.
      Further, fibroin had no effect on the activity of the insulin-sensitive
      downstream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and
      glycogen turnover independent of insulin action. In addition, fibroin upregulated
      glucose transporter (GLUT)1, which increased its expression at the cell surface
      and enhanced GLUT4 translocation. Together, these phenomena may underlie the
      improvement in diabetic hyperglycemia noted in vivo in response to fibroin.

PMID- 15570023
TI  - Metabolic adaptations of three inbred strains of mice (C57BL/6, DBA/2, and 129T2)
      in response to a high-fat diet.
AB  - Although it is now becoming more evident that the strain of mouse used to
      generate genetically modified models for the study of endocrine disorders
      contributes to the ensuing phenotype, metabolic characterization of these common
      strains used to produce genetically altered mice has been limited. The aim of
      this study therefore was to measure various metabolic parameters in C57BL/6,
      DBA/2, and 129T2 mice fed a control or a high-fat diet. Mice were fed either a
      control (7 g/100 g) or a high-fat (60 g/100 g) diet for 6 wk. During wk 6,
      spontaneous and voluntary physical activity and resting energy expenditure were
      determined. DBA/2 mice that consumed the control diet gained more weight and had
      larger regional fat pad depots than either C57BL/6 or 129T2 mice (P < 0.05).
      Spontaneous and voluntary activity was lower in 129T2 mice compared with DBA/2 or
      C57BL/6 mice (P < 0.05). Resting energy expenditure (corrected for body weight)
      was greater in C57BL/6 mice than in DBA/2 or 129T2 mice (P < 0.05), whereas
      glucose and fat oxidation did not differ among the 3 strains of mice. Plasma
      glucose concentrations in food-deprived mice were higher and insulin
      concentrations lower in 129T2 compared with C57BL/6 mice (P < 0.05), but were not
      affected by the high-fat diet in any of the 3 strains tested. This study shows
      that these 3 commonly used inbred strains of mice have different inherent
      metabolic characteristics. It further highlights that the background strain used
      to produce genetically modified mice is critical to the resultant phenotype.

PMID- 15570024
TI  - Diets containing soy protein isolate increase hepatic CYP3A expression and
      inducibility in weanling male rats exposed during early development.
AB  - Hepatic CYP3A enzymes were studied in weanling male Sprague-Dawley rats exposed
      to diets from gestational d 4 in which the sole protein source was either casein
      (CAS) or soy protein isolate (SPI). At age 25 d, rats were gavaged with corn oil
      or one of the CYP3A inducers, dexamethasone (DEX) and clotrimazole (CLT), at a
      dose of 50 mg/kg. Little CYP3A1 (CYP3A23), CYP3A2, or CYP3A9 mRNA was observed in
      CAS-fed weanling rats but CYP3A18 mRNA was readily detectable in Northern blots.
      In contrast, consumption of SPI without inducer treatment resulted in the
      expression of CYP3A1 (CYP3A23), and CYP3A2 mRNAs, expression of CYP3A apoprotein
      in hepatic microsomes, and a 2-fold greater turnover of the CYP3A substrate
      midazolam (P < 0.05). DEX induced CYP3A1, CYP3A2, and CYP3A9 (P < 0.05), but not
      CYP3A18 mRNA expression in rats fed both diets. Hepatic CYP3A apoprotein
      expression and midazolam 4-hydroxylation in SPI-fed rats was greater than that of
      CAS-fed rats after DEX treatment (P < 0.05). CLT also induced CYP3A2 mRNA 2-fold
      in rats fed both diets but CYP3A apoprotein expression in microsomes from SPI-fed
      CLT rats was double that of CLT-treated rats fed CAS (P < 0.05). The elevation of
      CYP3A apoprotein due to SPI and the CYP3A apoprotein induction by DEX and CLT
      treatment yielded no significant diet x inducer interaction. Analysis of
      heterologous nuclear RNA expression by RT-PCR using intron-specific primers for
      CYP3A1 revealed a 14-fold increase in RNA transcription in CAS-fed rats after
      treatment with DEX (P < 0.05) but no increase in rats fed SPI compared with rats
      fed CAS even though CYP3A1 mRNA and CYP3A apoprotein were significantly elevated.
      These data demonstrate that exposure to SPI during early development can increase
      CYP3A expression via post-transcriptional mechanisms and suggest that early soy
      consumption has potential effects on the metabolism of a wide variety of CYP3A
      substrates.

PMID- 15570025
TI  - Probiotic consumption does not enhance the cholesterol-lowering effect of soy in
      postmenopausal women.
AB  - Numerous studies report that soy lowers cholesterol. Probiotic bacteria were also
      reported to lower total cholesterol (TC) and LDL cholesterol (LDL-C). We
      hypothesized that by altering intestinal microflora, probiotic consumption may
      also change phytoestrogen metabolism and enhance the effects of soy. To evaluate
      the independent and interactive effects of probiotic bacteria and soy on plasma
      TC, LDL-C, HDL cholesterol (HDL-C), and triglycerides (TG), 37 women with a
      baseline TC of 5.24 mmol/L were given the following 4 treatments for 6 wk each in
      a randomized crossover design: soy protein isolate (26 +/- 5 g soy protein
      containing 44 +/- 8 mg isoflavones/d); soy protein isolate + probiotic capsules
      (10(9) colony-forming units Lactobacillus acidophilus DDS-1 and Bifidobacterium
      longum); milk protein isolate (26 +/- 5 g milk protein/d); and milk protein
      isolate + probiotic. Soy consumption decreased plasma TC by 2.2% (P = 0.02) and
      LDL-C by 3.5% (P = 0.005), increased HDL-C by 4.2% (P = 0.006) and tended to
      decrease TG (P = 0.07) compared with milk protein intake. When divided according
      to initial TC concentration, soy effects were observed only in
      hypercholesterolemic women (TC > 5.17 mmol/L). In this subgroup, soy treatments
      decreased plasma TC by 3.3% (P = 0.01), LDL-C by 4.5% (P = 0.004), and TG by
      10.6% (P = 0.02), and increased HDL-C by 4.2% (P = 0.02). When subjects were
      divided on the basis of plasma and urine concentrations of the isoflavone
      metabolite, equol, equol producers and nonproducers did not differ in baseline
      lipids or in the effects of soy. Probiotics did not lower cholesterol or enhance
      the effects of soy. These results confirm a beneficial effect of soy on plasma
      cholesterol in mildly hypercholesterolemic postmenopausal women independent of
      equol production status, but do not support an independent or additive effect of
      these particular probiotic bacteria.

PMID- 15570026
TI  - The unsaponifiable fraction of virgin olive oil in chylomicrons from men improves
      the balance between vasoprotective and prothrombotic factors released by
      endothelial cells.
AB  - Minor components of virgin olive oil (VOO) may play a key role in the beneficial
      effects of VOO on atherosclerosis. In the present study we evaluated the
      influence of the unsaponifiable fraction of VOO on the production of eicosanoids
      and nitric oxide (NO) by endothelial cells (HUVECs). Triglyceride-rich
      lipoprotein (TRLs) were isolated from human serum after the intake of meals
      enriched in 3 high-oleic acid oils, i.e., high-oleic sunflower (HOSO), VOO, or
      enriched-virgin olive (EVO) oils, the last-mentioned containing 2.4% of
      unsaponifiable matter. HOSO induced a greater accumulation of triglycerides (TGs)
      in the postprandial serum than VOO or EVO, as measured by calculating the area
      under the curve. The incubation with TRLs increased NO release by endothelial
      cells compared with untreated control cells, but the effects of the various TRLs
      did not differ. EVO-derived TRLs reduced the production of prostaglandin E(2)
      (PGE(2)) and thromboxane B(2) (TxB(2)) (the stable metabolite of TxA(2)) compared
      with VOO- or HOSO-derived TRLs. The release of PGI(2) (as 6-keto PGF(1alpha)) was
      similarly diminished by all TRLs compared with the control. In conclusion, the
      unsaponifiable fraction of VOO does not affect postprandial triglyceridemia, but
      it has favorable effects on endothelial function, mainly by reducing
      proinflammatory and vasoconstrictor eicosanoid synthesis (PGE(2) and TxB(2)).

PMID- 15570027
TI  - Dietary and biochemical selenium status of urban 6- to 24-month-old South Island
      New Zealand children and their postpartum mothers.
AB  - A community-based, cross-sectional survey was conducted in the South Island of
      New Zealand to assess the dietary and biochemical selenium status of children (n
      = 136) and their mothers (n = 302), and to assess factors influencing selenium
      status. Serum and plasma samples from children and their mothers were analyzed
      for selenium using graphite furnace atomic absorption spectrometry. Dietary
      selenium intakes were analyzed from 3-d weighed diet records, and food sources of
      selenium were quantified. Mean dietary selenium intakes in infants (6-11.9 mo),
      toddlers (12-24 mo), and mothers were below recommended levels. Toddlers had
      higher selenium intakes than infants (13.7 +/- 8.4 and 7.9 +/- 6.2 microg/d,
      respectively, P = 0.0001) and the selenium density of their diets was also higher
      [3.2 +/- 1.7 and 2.4 +/- 1.7 microg/(MJ . d), respectively, P = 0.003]. Household
      smoking was associated with lower serum selenium concentrations in infants and
      toddlers (P = 0.02). South Island women who were currently pregnant had lower
      plasma selenium concentrations (0.74 +/- 0.15 micromol/L) than nonpregnant
      lactating and nonpregnant nonlactating women (0.94 +/- 0.16 and 0.93 +/- 0.16
      micromol/L, respectively, P = 0.0001). Clearly, pregnant women, infants and
      toddlers are at risk of suboptimal selenium status, and further research is
      warranted to assess potential effects in these groups. The finding of an
      association between household smoking and lower selenium concentrations in
      children should be investigated further. Dietary interventions are recommended to
      improve dietary selenium intakes in South Island children and their mothers.

PMID- 15570028
TI  - Growth and diet quality are associated with the attainment of walking in rural
      Guatemalan infants.
AB  - The attainment of gross motor milestones is an important indicator of motor
      development in early life; however, little is known about factors affecting gross
      motor development in children from developing countries. The purpose of this
      study was to examine the relation of nutritional factors (physical growth and
      dietary intake) and morbidity during the first year of life to the age of walking
      without support. Multivariate regression models were used to analyze data
      collected prospectively between 1991 and 1999 in rural Guatemala. Attainment of
      children's gross motor milestones was assessed monthly by trained field workers
      using the 17-milestone Gross Motor Development Scale, morbidity was assessed by
      biweekly recall, and dietary intakes were measured at 9 and 12 mo of age using
      repeated 24-h dietary recalls. Median age of walking was 15 mo (range 10-24 mo; n
      = 174) with no differences by gender. Models were adjusted for birth order,
      gender, gestational age, maternal age and education, socioeconomic status, and
      community. Growth in length (-0.57 +/- 0.27 mo length for age Z-score; P = 0.04)
      and weight (-0.54 +/- 0.19 mo weight for age Z-score, P = 0.005) during the first
      year of life, rather than size at birth, predicted age of walking. Animal protein
      intake from complementary foods, while low (mean < 1 g/d) overall, was positively
      associated with earlier age of walking (P = 0.02). Morbidity during infancy was
      not associated with age of walking. These findings indicate the importance of
      prevention of postnatal growth retardation and improvement of diet quality for
      children's gross motor development.

PMID- 15570029
TI  - Particle size reduction and encapsulation affect the bioavailability of ferric
      pyrophosphate in rats.
AB  - Particle size is an important determinant of Fe absorption from poorly soluble Fe
      compounds in foods. Decreasing the particle size of elemental iron powders
      increases their absorption. The effect of a reduction in particle size on the
      bioavailability of ferric pyrophosphate (FePP) is unclear. Encapsulation of iron
      compounds for food fortification may protect against adverse sensory changes, but
      at the same time may reduce bioavailability. The hemoglobin (Hb) repletion method
      in weanling Sprague-Dawley rats (n = 100) was used to compare the relative
      bioavailability (RBV) of 4 forms of FePP: 1) regular FePP [mean particle size
      (MPS) approximately 21 microm]; 2) MPS approximately 2.5 microm; 3) MPS
      approximately 2.5 microm encapsulated in hydrogenated palm oil; and 4) MPS
      approximately 0.5 microm with emulsifiers. The RBV compared with ferrous sulfate
      was calculated by the slope-ratio technique. The RBV was 43% for encapsulated MPS
      approximately 2.5 microm, significantly lower than the other FePP compounds (P <
      0.05), 59% for the regular FePP, and 69% for MPS approximately 2.5 microm, not
      different from each other but significantly lower than ferrous sulfate (P <
      0.05), and 95% for emulsified MPS approximately 0.5 microm, comparable to ferrous
      sulfate. Encapsulation of FePP with hydrogenated palm oil at a capsule:substrate
      ratio of 60:40 decreased RBV. Particle size reduction increases the RBV of FePP
      and may make this compound more useful for food fortification.

PMID- 15570030
TI  - Dietary raw peas (Pisum sativum L.) reduce plasma total and LDL cholesterol and
      hepatic esterified cholesterol in intact and ileorectal anastomosed pigs fed
      cholesterol-rich diets.
AB  - Previous studies demonstrated the cholesterol-lowering effect of dietary legumes
      (mainly soybeans) in animals and humans, but the mechanisms by which they exert
      this effect are not completely understood. The contribution of the hindgut to
      this hypocholesterolemic effect is also not well documented. The present work was
      undertaken to investigate the effect of cholesterol-enriched (2.8 g/kg) casein
      (C) and raw pea seed (RP) diets on the cholesterol metabolism of intact (I) and
      ileorectal anastomosed (IRA) growing pigs. Four groups of 6 pigs were allocated
      to the treatments (C-I, C-IRA, RP-I, and RP-IRA pigs) for 3 wk. Plasma total
      cholesterol was lowered by the RP diet through a significant decrease in LDL
      cholesterol. The RP diet also decreased the hepatic concentration of esterified
      cholesterol and increased 3-hydroxy-3-methylglutaryl CoA reductase activity and
      LDL receptor synthesis. The biliary total cholesterol and bile acid
      concentrations were greater in RP- than in C-fed pigs. In addition, fecal bile
      acid output was higher in RP-fed pigs. The cecum-colon by-pass inhibited
      cholesterol and beta-sitosterol microbial transformation, lowered the bile acid
      output, and increased the primary to secondary bile acid output ratio, but its
      influence on cholesterolemia was negligible. These results suggest a
      hypocholesterolemic effect of the raw pea diet probably due to increased fecal
      bile acid output and an increased biliary bile acid concentration.

PMID- 15570031
TI  - Leucine supplementation has an anabolic effect on proteins in rabbit skin wound
      and muscle.
AB  - We investigated the effect of leucine supplementation on protein metabolism in
      skin wounds and muscle in anesthetized rabbits. l-[ring-(13)C(6)]phenylalanine
      was infused on d 7 after the ear was scalded, and the scalded ear and uninjured
      hindlimb were used as arteriovenous units to reflect protein kinetics in skin
      wounds and muscle. In comparison with a commercially available amino acid
      solution (10% Travasol), isonitrogenous [1638 micromol/(kg . h)] infusion of the
      amino acid solution with supplemental leucine to account for 35% of total
      nitrogen increased the net phenylalanine balance (P < 0.05) in the skin wound and
      muscle from -6.7 +/- 6.1 to 0.9 +/- 1.4 and from -4.4 +/- 2.4 to -1.0 +/- 0.4
      micromol/(100 g . h), respectively. Infusion of leucine alone did not
      significantly improve the net phenylalanine balance in either skin wounds [-4.0
      +/- 4.6 micromol/(100 g . h)] or muscle [-2.7 +/- 0.7 micromol/(100 g . h)]. We
      conclude that leucine supplementation had an anabolic effect on proteins in skin
      wounds and muscle, provided that adequate additional amino acids were also
      available.

PMID- 15570032
TI  - Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant
      women.
AB  - A well-planned vegetarian diet has been stated to be adequate during pregnancy.
      The aim of the present study was to compare serum vitamin B-12 and homocysteine
      concentrations in pregnant women (n = 109) consuming vegetarian and Western diets
      and to evaluate the adequacy of current dietary reference intakes of vitamin B-12
      for these women. Pregnant women adhering to vegetarian diets for at least 3 y,
      with subgroups of ovo-lacto vegetarians (OLVs; n = 27), low-meat eaters (LME, n =
      43), and women eating an average Western diet (control group, n = 39), were
      recruited. Dietary vitamin B-12 intake, serum vitamin B-12, and plasma total
      homocysteine (tHcy) concentrations were measured in wk 9-12, 20-22, and 36-38 of
      pregnancy. During pregnancy serum vitamin B-12 concentrations of ovo-lacto
      vegetarians (P < 0.001) and low-meat eaters (P = 0.050) were lower than those of
      the control group. We observed the combination of low serum vitamin B-12
      concentrations and elevated plasma tHcy in 22% of ovo-lacto vegetarians, in 10%
      of low-meat eaters, and in 3% of controls (P = 0.003). In OLVs, serum vitamin B
      12 predicted 60% of the plasma tHcy variation (P < 0.001), but in LMEs and
      controls only <10% (NS). Serum vitamin B-12 concentrations increased and plasma
      tHcy decreased sharply with increasing dietary intake of vitamin B-12 toward a
      cutoff point of 3 mug/d. Pregnant women consuming a long-term predominantly
      vegetarian diet have an increased risk of vitamin B-12 deficiency. Current
      recommended dietary intakes urgently need reevaluation.

PMID- 15570033
TI  - Dietary conjugated linoleic acids lower the triacylglycerol concentration in the
      milk of lactating rats and impair the growth and increase the mortality of their
      suckling pups.
AB  - Recent studies showed that conjugated linoleic acids (CLA) lower triacylglycerol
      concentrations in the milk of lactating animals. This study was performed to
      determine the reasons for this phenomenon; we also investigated whether there is
      a relation between altered lipid metabolism in the liver and the reduction in
      milk triacylglycerols in rats fed CLA. Two groups of female rats were fed diets
      containing 0 [sunflower oil (SFO) group] or 14.7 g/kg diet of a CLA mixture (CLA
      group) at the expense of sunflower oil during growth, pregnancy, and lactation.
      CLA-fed rats had 49 and 80% lower mRNA concentration and activity of fatty acid
      synthase, respectively, a 51% lower mRNA concentration of lipoprotein lipase
      (LPL) in their mammary glands at d 17 of lactation, and a 46% lower milk fat
      content than SFO rats (P < 0.05). Although CLA rats had lower concentrations of
      triacylglycerols in the liver than SFO rats (20.8 +/- 2.6 vs. 62.6 +/- 27.7
      micromol/g, P < 0.05), concentrations of triglycerides in plasma, which are the
      substrates of LPL, did not differ between the groups. Moreover, the number of
      pups per litter, litter weights, and pup weights at d 17 of lactation were 41,
      35, and 22% lower, respectively, in the CLA group than in the SFO group. In
      conclusion, the present study suggests that dietary CLA reduces triacylglycerol
      concentrations in the milk via reduced de novo fatty acid synthesis in the
      mammary gland and an impaired uptake of fatty acids from lipoproteins into the
      mammary gland. This might be the reason for reduced growth rates and an increased
      mortality of suckling pups.

PMID- 15570034
TI  - The cytotoxicity of vitamin E is both vitamer- and cell-specific and involves a
      selectable trait.
AB  - During a study of the effect of vitamin E in activated mouse macrophages, we
      observed a reduction in the viability of cells treated with various forms of
      vitamin E. We show in this report that some tocopherols (both gamma- and delta
      tocopherol) are cytotoxic to some but not all cell types. Mouse macrophages were
      especially sensitive (40 micromol/L), whereas human hepatocytes and bovine
      endothelial cells were almost completely refractory (90 micromol/L). The fully
      methylated tocopherol, alpha-tocopherol (alpha-Toc), was not cytotoxic in any
      cell type tested. The cytotoxicity observed with delta-tocopherol (delta-Toc) was
      associated with 2 markers of apoptosis. Vitamer-specific cytotoxicity was not due
      to differences in cellular uptake/accumulation because both alpha-Toc and delta
      Toc accumulated equally in any cell type tested. In contrast, the cell-specific
      cytotoxicity was related in part to uptake/accumulation of the tocopherols.
      Macrophages accumulated nearly 5 times more tocopherol compared with hepatocytes
      cultured under similar conditions. To address the hypothesis that uptake
      accounted for the cell-specific sensitivity, we developed a macrophage "subtype"
      that was markedly resistant (>150 micromol/L) to delta-Toc. Under many different
      cell culture conditions (including human serum) uptake/accumulation of
      tocopherols was reduced in this subtype by approximately 50%. Further selection
      and evaluation of this phenotype, however, demonstrated no cytotoxicity even when
      cellular levels were elevated. Our results show that undermethylated tocopherols
      are cytotoxic to macrophages and that there are independent and selectable
      processes that determine cellular tocopherol uptake/accumulation and delta-Toc
      cytotoxicity.

PMID- 15570035
TI  - Docosahexaenoic acid attenuates mycotoxin-induced immunoglobulin a nephropathy,
      interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation
      in mice.
AB  - The purpose of this investigation was to evaluate the dose-dependent effects of
      docosahexaenoic acid (DHA) on deoxynivalenol (DON)-induced IgA nephropathy in
      mice and their relation to proinflammatory gene expression and mitogen-activated
      protein kinase (MAPK) activation. Consumption of a modified AIN-93G diet
      containing 1, 5, and 30 g/kg DHA resulted in dose-dependent increases of DHA in
      liver phospholipids with concomitant decreases in arachidonic acid compared with
      control diets. DHA dose dependently inhibited increases in serum IgA and IgA
      immune complexes (IC) as well as IgA deposition in the kidney in DON-fed mice;
      the 30 g/kg DHA diet had the earliest detectable effects and maximal efficacy.
      Both splenic interleukin-6 (IL-6) mRNA and heterogeneous nuclear RNA (hnRNA), an
      indicator of IL-6 transcription, were significantly reduced in DON-fed mice that
      consumed 5 and 30 g/kg DHA; a similar reduction was observed for cyclooxygenase
      (COX-2) mRNA. In a subsequent study, acute DON exposure (25 mg/kg body weight)
      induced splenic IL-6 mRNA and hnRNA as well as COX-2 mRNA in mice fed the control
      diet, whereas induction of both RNA species was significantly inhibited in mice
      fed 30 g/kg DHA. These latter inhibitory effects corresponded to a reduction in
      DON-induced phosphorylation of p38, extracellular-signal related kinase 1/2, and
      c-Jun N-terminal kinase 1/2 MAPKs in the spleen. Taken together, the results
      indicate that DHA dose-dependently inhibited DON-induced IgA dysregulation and
      nephropathy, and that impairment of MAPK activation and expression of COX-2 and
      IL-6 are potential critical upstream mechanisms.

PMID- 15570036
TI  - Vitamin B-6 deficiency prolongs the time course of evoked dopamine release from
      rat striatum.
AB  - Vitamin B-6-deficient animals exhibit motor abnormalities. To investigate the
      possible physiologic alterations in the dopaminergic nervous system in vitamin B
      6 deficiency, dopamine release in the striatum of vitamin B-6-deficient rats was
      determined using in vivo electrochemistry. Male Sprague-Dawley rats, 3 wk old,
      weighing 50-60 g, were randomly assigned to a control (7 mg pyridoxine HCl/kg
      diet), vitamin B-6-deficient (0 mg pyridoxine HCl/kg diet), or pair-fed (7 mg
      pyridoxine HCl/kg diet) group. After 8 wk of dietary treatment, plasma
      concentrations of pyridoxal 5'-phosphate as well as the striatal pyridoxal 5'
      phosphate and pyridoxamine 5'-phosphate were significantly lower in the vitamin B
      6-deficient group than in the control and pair-fed groups. The dopamine
      concentrations of the striatum and the magnitude of the dopamine release after
      local application of KCl did not differ among the groups. However, the time
      required for KCl-evoked dopamine release to reach its peak level was
      significantly longer for the vitamin B-6-deficient rats than for controls. In
      addition, the decay time from the peak to one-half of the KCl-evoked dopamine
      release was also significantly prolonged in vitamin B-6-deficient rats compared
      with the control group. The results indicate that the cellular content of
      dopamine does not reflect the functional state of dopaminergic neurons in vitamin
      B-6 deficiency. The time course for release of dopamine and decay of the released
      dopamine is prolonged by vitamin B-6 deficiency, which might contribute to the
      motor abnormalities of the deficient rats.

PMID- 15570037
TI  - Adherence to the traditional mediterranean diet is inversely associated with body
      mass index and obesity in a spanish population.
AB  - The Mediterranean diet is a healthy eating pattern with protective effects on
      chronic diseases. The purpose of this study was to assess the relation between
      BMI and obesity and the level of adherence to the traditional Mediterranean diet.
      The subjects were Spanish men (n = 1547) and women (n = 1615) aged 25-74 y who
      were examined in 1999-2000, in a population-based, cross-sectional survey in the
      northeast of Spain (Girona). Dietary intake was assessed using a FFQ. A
      Mediterranean diet score, including foods considered to be characteristic
      components of the traditional Mediterranean diet (vegetables, fruits, pulses,
      nuts, fish, meat, cereals, olive oil, and wine) was created. An increase of 5 U
      in the dietary score was associated with a change in the BMI of 0.43 (P = 0.030)
      and 0.68 (P = 0.007), after controlling for potential confounders, in men and
      women, respectively. The obesity risk decreased in men (P = 0.010) and women (P =
      0.013) with increasing adherence to the traditional Mediterranean dietary
      pattern. The population in the top tertile of this score were less likely to be
      obese in both genders [odds ratio (OR) and (95% CI): 0.61 (0.40-0.92) in men;
      0.61 (0.40-0.93) in women] after adjusting for potential confounders. These data
      suggest that the traditional Mediterranean dietary pattern is inversely
      associated with BMI and obesity. This finding may be useful in the development of
      dietary approaches for dietary counseling and the prevention of obesity.

PMID- 15570038
TI  - Dietary carotenoids and genetic instability modify bladder cancer risk.
AB  - In vitro and in vivo studies have shown that carotenoid supplementation is
      associated with decreased DNA damage, but the role of dietary carotenoids in
      cancer risk remains controversial because epidemiologic studies have yielded
      conflicting results. Limited data exist regarding the role of dietary carotenoids
      in the context of constitutional genetic instability in cancer risk. This case
      control study estimated dietary carotenoid intake [microg/(kJ . d)] from a FFQ
      for 423 patients with bladder cancer and 467 healthy controls, and quantified
      baseline and benzo[a]pyrene diol epoxide (BPDE)- and gamma-radiation-induced DNA
      damage in the peripheral blood lymphocytes using the comet assay. Overall, intake
      of total carotenoids was lower (P < 0.01) for bladder cancer cases (mean +/- SD:
      1273.4 +/- 688.9) compared with healthy controls (1501.3 +/- 791.5). When
      categorized into quartiles, there was an inverse association between increasing
      levels of carotenoid intake and bladder cancer risk with greatest protective
      effect [odds ratio (OR) = 0.56, 95% CI, 0.37-0.85] in the quartile with the
      highest level of intake. Baseline and mutagen-induced DNA damage was
      significantly higher in cases than in controls; when analyzed jointly with
      carotenoid intake, high DNA damage and low carotenoid intake were associated with
      the highest risk. For example, with high baseline DNA damage and low total
      carotenoid intake, the OR was 3.08 (95% CI, 1.64-5.77); with high baseline DNA
      damage and high total carotenoid intake, the risk was somewhat attenuated (OR =
      2.49, 95% CI, 1.28-4.84). The risk was decreased further for low baseline DNA
      damage and low total carotenoid intake (OR = 2.18; 95% CI, 1.13-4.22). This study
      provides evidence of a preventive role for carotenoids in bladder cancer, and
      these data may have important implications for cancer prevention, especially for
      individuals susceptible to DNA damage.

PMID- 15570039
TI  - Dietary exposure to whey proteins alters rat mammary gland proliferation,
      apoptosis, and gene expression during postnatal development.
AB  - We have found that AIN-93G diets made with whey protein hydrolysate (WPH) reduce
      7,12-dimethyl-benz[a]anthracene (DMBA)-induced tumor incidence in Sprague-Dawley
      (Harlan) rats relative to those fed a diet with casein (CAS). Herein, we
      replicated these findings in another Sprague-Dawley substrain (Charles River) and
      examined whether WPH protective effects were associated with altered mammary
      gland differentiation status and expression of the tumor suppressor phosphatase
      and tensin homolog deleted in chromosome ten (PTEN). Mammary tumor incidence was
      lower in DMBA-treated rats fed WPH than in those fed CAS. Mammary glands of WPH-
      and CAS-fed rats were isolated at weaning [postnatal day (PND) 21-28] and at an
      early adult stage (PND 50-53) and analyzed for proliferative (proliferating cell
      nuclear antigen immunoreactivity), apoptotic (terminal deoxynucleotidyl
      transferase-mediated deoxy-UTP nick-end labeling), and differentiation (beta
      casein) indices, as well as for PTEN mRNA and protein levels. PND 50-53 rats fed
      WPH showed decreased proliferation and increased apoptosis in mammary structures,
      coincident with increased mammary beta-casein gene expression, decreased terminal
      end-bud numbers, and increased ductal lengths, relative to same-age CAS-fed rats.
      When challenged with DMBA for 24 h, mammary glands of PND 53 CAS-fed rats had
      decreased cell survival in both terminal end buds and ductal epithelium, while
      the mammary glands of WPH-fed rats were not altered from pre-DMBA levels. At 7 d
      post-DMBA, mammary glands of CAS- and WPH-fed rats exhibited comparable apoptotic
      indices. Mammary PTEN expression was higher in WPH- than in CAS-fed rats at PND
      21-28, but was not different in young adults fed either diet. Results demonstrate
      that dietary WPH advances mammary gland differentiation during neonatal
      development and suggest that the transiently increased expression of the pro
      apoptotic signal PTEN during a sensitive developmental window may partly underlie
      the cancer protective effects of WPH.

PMID- 15570040
TI  - Development of an assay to quantify rumen ciliate protozoal biomass in cows using
      real-time PCR.
AB  - Currently used microbial markers cannot distinguish protozoal nitrogen (N) from
      bacterial N, thus limiting research on protozoal quantification in vivo by the
      lack of a repeatable, accurate marker for protozoal N. We report the development
      of a real-time PCR assay targeting the gene encoding 18S rDNA to quantify the
      amount of protozoal biomass in ruminal fluid and duodenal digesta. Protozoal
      cells were harvested from rumen fluid and concentrated for evaluation of recovery
      of rDNA in samples from the rumen and the duodenum. The DNA from concentrated
      cells was extracted with virtually 100% efficiency both before and after column
      purification. After serial spiking of protozoal cells into duodenal fluid over
      the entire range of quantification, the recovery was highly linear and constant
      at 81%. After serially spiking increasing quantities of protozoal rDNA into a
      constant volume of duodenal samples, nonlinear regression verified constant
      recovery of background rDNA in duodenal samples regardless of the ratio of
      target:nontarget rDNA. Recommendations for the procedure, including replication
      per sample, are described herein.

PMID- 15570041
TI  - alpha-linolenic acid, coronary heart disease, and prostate cancer.

PMID- 15570043
TI  - Review of the International Research Conference on Food, Nutrition, and Cancer,
      2004.

PMID- 15570044
TI  - Effects of energy balance on cancer in genetically altered mice.
AB  - Evidence has accumulated from laboratory-based animal experiments and population
      based human epidemiological studies that lifestyle factors that affect energy
      balance, such as caloric intake, nutritional status, and exercise, act in concert
      with genetic susceptibility to influence cancer development and progression. The
      use of animal models with specific genetic alterations, in combination with
      lifestyle modifications that alter overall energy balance, has contributed to a
      greater understanding of the mechanistic changes occurring during carcinogenesis
      and to the identification of points of intervention. Studies in our laboratory
      focusing on the role of energy balance and genetic susceptibility in mice
      deficient in one (+/-) or both (-/-) alleles of the p53 tumor suppressor gene and
      mice with a mutant APC allele (APC(Min)) showed that calorie restriction
      decreases tumor burden, increases tumor latency, and decreases serum insulin-like
      growth factor (IGF)-1 and leptin levels. Data from our studies, combined with
      results from other animal and human studies, have established a role for IGF-1 in
      carcinogenesis. Studies using genetic models of cancer that have been interbred
      with mice with abnormal levels of IGF-1 will enable the examination of combined
      effects of energy balance and genetic alterations on the cancer process. Models
      that integrate lifestyle and genetic effects in a single system provide a
      physiologically intact system in which combination interventions and therapies
      for cancer prevention can be tested and validated, thus building a strong
      preclinical foundation that will inform the development of clinical trials and
      add perspective to epidemiological studies.

PMID- 15570045
TI  - Breast cancer and the brain: a neurodevelopmental hypothesis to explain the
      opposing effects of caloric deprivation during the Dutch famine of 1944-1945 on
      breast cancer and its risk factors.
AB  - Most studies on calorie deprivation and cancer risk in rodents show reductions in
      tumor occurrence. However, the few human studies on calorie restriction are
      conflicting. An overview is given of results in the DOM (diagnostic onderzoek
      mammacarcinoom) cohorts among women exposed to the Dutch Famine of 1944-1945.
      Opposing effects were found on risk factors (shortening of leg length, later
      menarche, and earlier menopause), whereas urinary estrogens and plasma insulin
      like growth factor (IGF)-1 and IGF binding protein-3 were increased, as was
      breast cancer itself. Exposure between 2 and 10 y old was an unexpected window of
      susceptibility to the effects of calorie deprivation. The effects of famine
      exposure were most clearly seen in women who never gave birth. These opposing
      observations can be explained by a neurodevelopmental hypothesis on set-point
      shifts at the level of the diencephalons/hypothalamus, either directly or from
      rebound effects. Such a mechanism reflects old evolutionary adaptation systems in
      lower and higher organisms to cope with periods of stress and famine by
      adjusting, for example, reproductive functions. These effects in exposed women
      may later also affect their unexposed offspring. This hypothesis provides several
      testable, hormone-mediated corollaries on the relationships between the role of
      calories in a Westernized lifestyle and human cancer risk. The underlying
      developmental perspective, as opposed to a risk factor approach, can explain why
      certain ages, even before breast development, are especially sensitive to effects
      of large fluctuations in calories. The observations presented may have
      implications for preventive strategies such as promoting moderation of calorie
      intake to curb cancer risks.

PMID- 15570046
TI  - Weight control and breast cancer prevention: are the effects of reduced energy
      intake equivalent to those of increased energy expenditure?
AB  - Failure to prevent adult weight gain is associated with an elevated risk for
      breast cancer. In general, an increase in body weight is accounted for by excess
      energy intake relative to energy expenditure. Efforts to control weight gain
      usually involve either a reduction in energy intake via dietary energy
      restriction (DER), an increase in energy expenditure via physical activity (PA),
      or both. However, it is not clear whether preventing weight gain by DER, PA, or
      their combination has comparable effects on the risk for cancer. Results from
      preclinical models indicate that DER results in a highly reproducible and dose
      dependent inhibition of experimentally induced breast cancer. PA also inhibits
      mammary carcinogenesis, but whether these effects depend on energy balance is not
      clear. Emerging evidence indicates that reduced levels of circulating insulin
      like growth factor (IGF) 1 (IGF-1) and elevated levels of corticosterone may be
      involved in DER-mediated protection against cancer; however, conditions of PA
      reported to protect against cancer can actually increase circulating levels of
      IGF-1. Mechanistic studies have shown that DER inhibits cell proliferation,
      creates a proapoptotic environment, and reduces blood vessel density adjacent to
      premalignant and malignant mammary pathologies; comparable information is not
      available from preclinical studies of PA and carcinogenesis. Additional research
      is needed to investigate the equivalence of DER, PA, and their combination in
      breast cancer prevention under comparable conditions of energy balance.

PMID- 15570047
TI  - Long-chain (n-3) fatty acid intake and risk of cancers of the breast and the
      prostate: recent epidemiological studies, biological mechanisms, and directions
      for future research.
AB  - The association between dietary (n-3) fatty acids and hormone-responsive cancers
      continues to attract considerable attention in epidemiological, clinical, and
      experimental studies. We previously reviewed the epidemiological literature on
      the association between hormone-responsive cancers and the long-chain fatty acids
      eicosapentaenoic acid and docosahexaenoic acid. We concluded that the compelling
      evidence from ecological studies, animal models, and mechanistic experiments in
      vitro was not supported clearly by the available epidemiological data. To various
      degrees, epidemiological studies published more recently attempted to address
      some of the methodological limitations plaguing earlier studies by using
      validated questionnaires, examining specific fatty acids and their
      interrelationships, and adjusting estimates for a wider range of potentially
      confounding factors than in previous studies. In this review, our aim was to
      update the previous review with the results of recent epidemiological studies and
      to discuss possible biological mechanisms and directions for future research.

PMID- 15570048
TI  - Dietary (n-6) PUFA and intestinal tumorigenesis.
AB  - Cancer is the second leading cause of death in the United States, and mortality
      due to colorectal cancer is only surpassed by lung cancer. Epidemiological
      studies demonstrate that dietary polyunsaturated fats can have a profound effect
      on colorectal cancer risk. Experimental data indicate that modulation of cellular
      (n-6) PUFA metabolism can affect the progression of the disease. This paper
      discusses the role (n-6) PUFA play in promoting intestinal tumorigenesis and how
      dietary PUFA from different families interact to modify the neoplastic process.
      Dietary PUFA that attenuate arachidonic acid metabolism [such as (n-3) PUFA] have
      antineoplastic properties, whereas those that augment arachidonic acid
      metabolism, such as linoleic, gamma-linolenic, and arachidonic acids do not
      appear to enhance tumorigenesis when added to the Western diet but may diminish
      the beneficial effects of other dietary lipids. It is the relative contributions
      of the different dietary PUFA that may determine overall risk for and progression
      of the disease.

PMID- 15570049
TI  - (n-3) fatty acids and cancer therapy.
AB  - Supplementing the diet of tumor-bearing mice or rats with oils containing (n-3)
      (omega-3) or with purified (n-3) fatty acids has slowed the growth of various
      types of cancers, including lung, colon, mammary, and prostate. The efficacy of
      cancer chemotherapy drugs such as doxorubicin, epirubicin, CPT-11, 5
      fluorouracil, and tamoxifen, and of radiation therapy has been improved when the
      diet included (n-3) fatty acids. Some potential mechanisms for the activity of (n
      3) fatty acids against cancer include modulation of eicosanoid production and
      inflammation, angiogenesis, proliferation, susceptibility for apoptosis, and
      estrogen signaling. In humans, (n-3) fatty acids have also been used to suppress
      cancer-associated cachexia and to improve the quality of life. In one study, the
      response to chemotherapy therapy was better in breast cancer patients with higher
      levels of (n-3) fatty acids in adipose tissue [indicating past consumption of (n
      3) fatty acids] than in patients with lower levels of (n-3) fatty acids. Thus, in
      combination with standard treatments, supplementing the diet with (n-3) fatty
      acids may be a nontoxic means to improve cancer treatment outcomes and may slow
      or prevent recurrence of cancer. Used alone, an (n-3) supplement may be a useful
      alternative therapy for patients who are not candidates for standard toxic cancer
      therapies.

PMID- 15570050
TI  - A review of the health effects of green tea catechins in in vivo animal models.
AB  - There is good evidence from in vitro studies that green tea catechins have a role
      in protection against degenerative diseases. However, the concentrations used in
      vitro are often higher than those found in animal or human plasma, and so in vivo
      evidence is required to demonstrate any protective effect of catechins. This
      article summarizes the most interesting in vivo animal studies on the protective
      effects of green tea catechins against biomarkers for cancer, cardiovascular
      disease, and other degenerative diseases. Generally, most studies using animal
      models show that consumption of green tea (catechins) provides some protection,
      although most studies have not examined dose response. Tea catechins could act as
      antitumorigenic agents and as immune modulators in immunodysfunction caused by
      transplanted tumors or by carcinogen treatment. Green tea has antiproliferative
      activity in hepatoma cells and hypolipidemic activity in hepatoma-treated rats,
      and some studies report that it prevents hepatoxicity. It could act as a
      preventive agent against mammary cancer postinitiation. Nevertheless, the
      implications of green tea catechins in preventing metastasis have not been
      clearly established. Long-term feeding of tea catechins could be beneficial for
      the suppression of high-fat diet-induced obesity by modulating lipid metabolism,
      could have a beneficial effect against lipid and glucose metabolism disorders
      implicated in type 2 diabetes, and could also reduce the risk of coronary
      disease. Further investigations on mechanisms, the nature of the active
      compounds, and appropriate dose levels are needed.

PMID- 15570051
TI  - The dietary phytochemical chlorophyllin alters E-cadherin and beta-catenin
      expression in human colon cancer cells.
AB  - Chlorophyllin (CHL), an anticarcinogenic and antimutagenic water-soluble
      derivative of chlorophyll, has been reported to induce apoptosis in human colon
      cancer cells via a pathway involving cell differentiation. Induction of
      differentiation markers may be important in limiting cancer-cell invasion and
      metastasis, and there is much interest in understanding the underlying
      mechanisms, because this might provide insights for cancer chemotherapy. In the
      present study, human HCT116 colon-cancer cells were treated with CHL, and the
      expression levels of E-cadherin and beta-catenin were examined using
      immunocytochemistry and laser scanning confocal microscopy. E-cadherin was
      detected almost exclusively at the cell periphery of cancer cells treated with or
      without CHL, but the expression of E-cadherin in the plasma membrane was markedly
      elevated in the cells treated with CHL. beta-Catenin also was strongly expressed
      in the plasma membrane, especially after CHL treatment. No change in the
      expression of beta-catenin mRNA was detected across a broad range of CHL
      concentrations (10-500 micromol/L), but there was a concentration-dependent
      decrease in nuclear beta-catenin protein levels without overt changes in the
      cytosolic pool of beta-catenin. Our interpretation of these findings is that CHL
      induces E-cadherin expression, and this facilitates trafficking of beta-catenin
      away from the nucleus and into the plasma membrane, possibly for destruction via
      the adherins junction remodeling (Hakai) pathway.

PMID- 15570052
TI  - Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary
      cancer in rats is diet dependent.
AB  - Many popular dietary supplements are enriched in polyphenols such as the soy
      isoflavones, tea catechins, and resveratrol (from grape skins), each of which has
      been shown to have chemopreventive activity in cellular models of cancer. The
      proanthocyanidins, which are oligomers of the catechins, are enriched in grape
      seeds and form the basis of the dietary supplement grape seed extract (GSE).
      Evidence suggests that the proanthocyanidins may be metabolized to the monomeric
      catechins. This study was carried out to determine whether GSE added to rodent
      diets protected against carcinogen-induced mammary tumorigenesis in rats and
      whether this was affected by the composition of the whole diet. Female rats were
      begun on 5%, 1.25%, or 0% (control) GSE-supplemented diets at age 35 d. At age 50
      d they were administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil at
      80 mg/kg body weight. They were weighed and monitored weekly for tumor
      development until 120 d after DMBA administration. Administration of GSE in AIN
      76A diet did not show any protective activity of GSE against DMBA-induced breast
      cancer. However, administration of GSE in a laboratory dry food diet (Teklad 4%
      rodent diet) resulted in a 50% reduction in tumor multiplicity. In similar
      experiments, genistein administered in AIN-76A diet also failed to show
      chemopreventive activity against the carcinogen N-methyl-N-nitrosourea; however,
      when administered at the same dose in the Teklad 4% rodent diet, genistein
      exhibited significant chemopreventive activity (44-61%). These results
      demonstrate that GSE is chemopreventive in an animal model of breast cancer;
      moreover, the diet dependency of the chemopreventive activity for both GSE and
      genistein suggests that whether or not a compound is chemopreventive may depend
      on the diet in which the agent is administered.

PMID- 15570053
TI  - New aspects in vitamin a metabolism: the role of retinyl esters as systemic and
      local sources for retinol in mucous epithelia.
AB  - Vitamin A and its active metabolites are important for growth and differentiation
      of a variety of cells, mainly in mucosa-associated epithelia, where they exhibit
      a wide spectrum of activities. Vitamin A, stored as retinyl esters (REs), is
      delivered from liver stores into the bloodstream as retinol bound to retinol
      binding protein. This process is regulated homeostatically, ending up in a more
      or less constant plasma retinol level. In situations of a high vitamin A demand
      (e.g., inflammation, diseases, prenatal period), this supply can be insufficient
      because of delayed production of retinol binding protein, leading to local
      deficiencies and impairment of structure and function in the respective tissues.
      This delay may be overcome by cellular RE stores. Several cell types, including
      buccal mucosa cells, can take up RE. Retinyl palmitate is taken up when it is
      applied topically to either metaplastically mutated rat vaginal epithelium (as a
      gel) or to human meta- and dysplastic bronchial epithelia (via inhalation) that
      have a vitamin A deficiency. In rats and humans, the modified epithelia can be
      normalized, at least in part. In conclusion, topically applied retinyl esters may
      be a promising therapy for local retinol deficiencies and may reverse the
      morphological alterations of the epithelium in tissues that are vitamin A
      deficient.

PMID- 15570054
TI  - Vitamin E and breast cancer.
AB  - Vitamin E is a term that describes a group of compounds with similar yet unique
      chemical structures and biological activities. One interesting property possessed
      by certain vitamin E compounds-namely, delta-tocotrienol, RRR-alpha-tocopheryl
      succinate [vitamin E succinate (VES), a hydrolyzable ester-linked succinic acid
      analogue of RRR-alpha-tocopherol], and a novel vitamin E analogue referred to as
      alpha-TEA (alpha-tocopherol ether linked acetic acid analogue, which is a stable
      nonhydrolyzable analogue of RRR-alpha-tocopherol)-is their ability to induce
      cancer cells but not normal cells to undergo a form of cell death called
      apoptosis. In contrast, the parent compound, RRR-alpha-tocopherol, also referred
      to as natural or authentic vitamin E and known for its antioxidant properties,
      does not induce cancer-cell apoptosis. Efforts to understand how select vitamin E
      forms can induce cancer cells to undergo apoptosis have identified several
      nonantioxidant biological functions, including restoration of pro-death
      transforming growth factor-beta and Fas signaling pathways. Recent studies with
      alpha-TEA show it to be a potent inducer of apoptosis in a wide variety of
      epithelial cancer cell types, including breast, prostate, lung, colon, ovarian,
      cervical, and endometrial in cell culture, and to be effective in significantly
      reducing tumor burden and metastasis in a syngeneic mouse mammary tumor model, as
      well as xenografts of human breast cancer cells. Studies also show that alpha
      TEA, in combination with the cyclooxygenase-2 inhibitor celecoxib and the
      chemotherapeutic drug 9-nitro-camptothecin decreases breast cancer animal model
      tumor burden and inhibits metastasis significantly better than do single-agent
      treatments.

PMID- 15570055
TI  - Vitamin D and colon carcinogenesis.
AB  - Colorectal cancer is the third most commonly occurring cancer in the United
      States and accounts for approximately 11% of cancer deaths. Many epidemiological
      studies have shown an association between dietary factors, including calcium and
      vitamin D, and the incidence of colon cancer. Recently the Calcium Polyp
      Prevention Study demonstrated that calcium supplementation can reduce the
      recurrence of colon polyps, but the effect depends on serum vitamin D levels. We
      used the Apc(min) mouse model of intestinal cancer to investigate the effects of
      vitamin D treatment and calcium intake independently on polyp formation. We found
      that 1,25-dihydroxycholecaliferol was potent in inhibiting tumor load; however,
      the dose used to achieve this antiproliferative effect led to deleterious effects
      on serum calcium homeostasis. These effects were minimized by use of a synthetic
      analogue with reduced toxicity. Additionally, we tested the effect of a modified
      calcium diet in Apc(min) mice but did not find a protective effect, perhaps
      because of a reduction in circulating levels of 25-hydroxycholecaliferol with
      increasing levels of dietary calcium. A number of other studies that use rodent
      models with vitamin D supplementation or deficiency illustrate the efficacy of
      vitamin D in colon cancer prevention. The mechanisms of direct action of vitamin
      D on colonic epithelium include regulation of growth factor and cytokine
      synthesis and signaling, as well as modulation of the cell cycle, apoptosis, and
      differentiation. Because of the apparent synergistic effect of vitamin D and
      calcium, cosupplementation of both nutrients in cancer prevention programs may be
      advised.

PMID- 15570056
TI  - Vitamin D and skin cancer.
AB  - Skin cancer is the most common cancer afflicting humans. These cancers include
      melanomas and 2 types of malignant keratinocytes: basal-cell carcinomas (BCC) and
      squamous-cell carcinomas (SCC). UV light exposure is linked to the incidence of
      these cancers. On the other hand, the skin is the major source of vitamin D-3
      (cholecalciferol) and UV light is critical for its formation. Keratinocytes can
      convert vitamin D-3 to its hormonal form, 1,25 dihydroxyvitamin D(3)
      [1,25(OH)(2)D(3)] (calcitriol). 1,25(OH)(2)D(3) in turn stimulates the
      differentiation of keratinocytes, raising the hope that 1,25(OH)(2)D(3) may
      prevent the development of malignancies in these cells. We identified a number of
      mechanisms by which 1,25(OH)(2)D(3) regulates the differentiation of
      keratinocytes and explored where this regulation breaks down in SCCs.
      1,25(OH)(2)D(3) regulates gene expression by activating the vitamin D receptor
      (VDR). When activated, the VDR binds to one of two coactivator complexes: DRIP or
      p160/SRC. Binding to DRIP occurs in the undifferentiated keratinocyte, but, as
      the cell differentiates, DRIP(205) levels fall and p160/SRC binding takes over as
      SRC3 expression increases. SCCs fail to respond to the prodifferentiating actions
      of 1,25(OH)(2)D(3). These cells have normal levels of VDR and normal binding of
      VDR to vitamin D response elements. However, they overexpress DRIP(205) such that
      the p160/SRC complex is blocked from binding to VDR. We hypothesize that failure
      of 1,25(OH)(2)D(3) to induce differentiation in SCCs lies at least in part with
      its failure to induce the replacement of the DRIP complex with the SRC complex in
      the promoters of genes required for differentiation.

PMID- 15570057
TI  - Potential synergy of phytochemicals in cancer prevention: mechanism of action.
AB  - Epidemiological studies have consistently shown that regular consumption of
      fruits and vegetables is strongly associated with reduced risk of developing
      chronic diseases, such as cancer and cardiovascular disease. It is now widely
      believed that the actions of the antioxidant nutrients alone do not explain the
      observed health benefits of diets rich in fruits and vegetables, because taken
      alone, the individual antioxidants studied in clinical trials do not appear to
      have consistent preventive effects. Work performed by our group and others has
      shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant
      and antiproliferative activities and that the major part of total antioxidant
      activity is from the combination of phytochemicals. We proposed that the additive
      and synergistic effects of phytochemicals in fruits and vegetables are
      responsible for these potent antioxidant and anticancer activities and that the
      benefit of a diet rich in fruits and vegetables is attributed to the complex
      mixture of phytochemicals present in whole foods. This explains why no single
      antioxidant can replace the combination of natural phytochemicals in fruits and
      vegetables to achieve the health benefits. The evidence suggests that
      antioxidants or bioactive compounds are best acquired through whole-food
      consumption, not from expensive dietary supplements. We believe that a
      recommendation that consumers eat 5 to 10 servings of a wide variety of fruits
      and vegetables daily is an appropriate strategy for significantly reducing the
      risk of chronic diseases and to meet their nutrient requirements for optimum
      health.

PMID- 15570058
TI  - Tomato phytochemicals and prostate cancer risk.
AB  - Mounting evidence over the past decade suggests that the consumption of fresh and
      processed tomato products is associated with reduced risk of prostate cancer. The
      emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may
      be the principle phytochemical responsible for this reduction in risk. A number
      of potential mechanisms by which lycopene may act have emerged, including serving
      as an important in vivo antioxidant, enhancing cell-to-cell communication via
      increasing gap junctions between cells, and modulating cell-cycle progression.
      Although the effect of lycopene is biologically relevant, the tomato is also an
      excellent source of nutrients, including folate, vitamin C, and various other
      carotenoids and phytochemicals, such as polyphenols, which also may be associated
      with lower cancer risk. Tomatoes also contain significant quantities of
      potassium, as well as some vitamin A and vitamin E. Our laboratory has been
      interested in identifying specific components or combination of components in
      tomatoes that are responsible for reducing prostate cancer risk. We carried out
      cell culture trials to evaluate the effects of tomato carotenoids and tomato
      polyphenols on growth of prostate cancer cells. We also evaluated the ability of
      freeze-dried whole-tomato powder or lycopene alone to reduce growth of prostate
      tumors in rats. This paper reviews the epidemiological evidence, evaluating the
      relationship between prostate cancer risk and tomato consumption, and presents
      experimental data from this and other laboratories that support the hypothesis
      that whole tomato and its phytochemical components reduce the risk of prostate
      cancer.

PMID- 15570059
TI  - Indole-3-carbinol and prostate cancer.
AB  - Epidemiological and dietary studies have revealed an association between high
      dietary intake of cruciferous vegetables and decreased prostate cancer risk. Our
      studies have shown that indole-3-carbinol (I3C), a common phytochemical in
      cruciferous vegetables, and its in vivo dimeric product 3,3'-diindolylmethane
      (DIM) upregulate the expression of phase I and phase II enzymes, suggesting
      increased capacity for detoxification and inhibition of carcinogens. Studies from
      our laboratory and others have found that I3C can induce G1 cell-cycle arrest and
      apoptosis in prostate cancer cells. In addition, we found, by microarray gene
      expression profiling, that I3C and DIM regulate many genes that are important for
      the control of cell cycle, cell proliferation, signal transduction, and other
      cellular processes, suggesting the pleiotropic effects of I3C and DIM on prostate
      cancer cells. We recently found that I3C functions as an inhibitor of Akt and
      nuclear factor kappaB (NF-kappaB), which play important roles in cell survival
      and which are believed to be potential targets in cancer therapy. Studies have
      already shown that the inactivation of Akt and NF-kappaB is responsible for
      chemosensitization of chemoresistant cancer cells. Because there is no effective
      treatment strategy for hormone-dependent and, most importantly, hormone
      independent and metastatic prostate cancer, our strategies to sensitize prostate
      cancer cells to a chemotherapeutic agent by I3C and DIM is a novel breakthrough
      that could be used for devising novel therapies for prostate cancer. In
      conclusion, the results from our laboratory and from others provide ample
      evidence for the benefit of I3C and DIM for the prevention and the treatment of
      prostate cancer.

PMID- 15570060
TI  - Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone
      oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by
      broccoli seeds and isothiocyanates.
AB  - Cruciferous vegetables contain glucosinolates that, after conversion to
      isothiocyanates (ITC), are capable of inducing cytoprotective genes. We examined
      whether broccoli seeds can elicit a chemoprotective response in mouse organs and
      rodent cell lines and investigated whether this response requires nuclear factor
      erythroid 2 p45-related factor 2 (Nrf2). The seeds studied contained
      glucosinolate at 40 mmol/kg, of which 59% comprised glucoiberin, 19% sinigrin, 8%
      glucoraphanin, and 7% progoitrin. Dietary administration of broccoli seeds to
      nrf2(+/+) and nrf2(-/-) mice produced a approximately 1.5-fold increase in
      NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase (GST)
      activities in stomach, small intestine, and liver of wild-type mice but not in
      mutant mice; increased transferase activity was associated with elevated levels
      of GSTA1/2, GSTA3, and GSTM1/2 subunits. These seeds also increased significantly
      the level of glutamate cysteine ligase catalytic (GCLC) subunit in the stomach
      and the small intestine of nrf2(+/+) mice but not nrf2(-/-) mice. An aqueous
      broccoli seed extract was prepared for treatment of cultured cells that contained
      ITC at approximately 600 mumol/L, composed of 61% 3-methylsulfinylpropyl ITC, 30%
      sulforaphane, 4% allyl ITC, and 4% 3-butenyl ITC. This extract induced GSTA1/2,
      GSTA3, NQO1, and GCLC between 3-fold and 10-fold in mouse Hepa-1c1c7 and rat
      liver RL-34 cells. The broccoli seed extract affected increases in GSTA3, GSTM1,
      and NQO1 proteins in nrf2(+/+) mouse embryonic fibroblasts but not in nrf2(-/-)
      mouse embryonic fibroblasts. These experiments show that broccoli seeds are
      effective at inducing antioxidant and detoxication proteins, both in vivo and ex
      vivo, in an Nrf2-dependent manner.

PMID- 15570061
TI  - Clinical trials in cancer prevention: current results and perspectives for the
      future.
AB  - Cancer prevention remains the ideal strategy for reducing the burden of cancer on
      society. Progress in cancer prevention has been accelerated as prevention
      clinical trials are completed and reported. A promising strategy is the
      identification of cancer risk factors through epidemiologic and experimental
      research with lifestyle and medical approaches that allow translation of clinical
      trial results to clinical practice. A major focus of cancer prevention clinical
      trials has been on modulation of hormones and nutritional modifications using
      natural or synthetic bioactive food components for breast and prostate cancer.
      Breast cancer prevention clinical trials have investigated the role of estrogen
      antagonists with agents such as tamoxifen, raloxifene, and newer agents such as
      aromatase inhibitors and bioactive food components. Among the promising bioactive
      food components being investigated at the National Cancer Institute in prevention
      clinical trials to reduce breast cancer risk are indole-3-carbinol,
      sulforaphanes, phytoestrogen isoflavones, perillyl alcohol, and green tea
      polyphenols. Prostate cancer prevention trials have focused on hormone modulation
      with the 5-alpha-reductase inhibitor finasteride and bioactive food components
      such as selenium and vitamin E. Soy isoflavones, green tea polyphenols, and
      doxercalciferol also are being investigated for prostate cancer prevention.
      Future prevention clinical trials will rely on multidisciplinary medical
      approaches that bring together expertise in many fields to address disease across
      the cancer spectrum. Nutritional science can play an important role in this
      effort through the use of new and emerging technologies to better understand the
      influence of bioactive food components on the genes, proteins, and cellular
      processes that are associated with cancer risk.

PMID- 15570062
TI  - Diet and cancer prevention: evidence-based medicine to genomic medicine.
AB  - The practice of medicine, including health promotion and disease prevention, is
      on the verge of being revolutionized once again as the scientific and medical
      community transitions from evidence-based medicine to genomic medicine. Evidence
      based medicine entails the systematic approach of formulating a question,
      developing literature search strategies, and evaluating and applying evidence to
      establish clinical practice guidelines. In 1982, when the National Research
      Council published the first comprehensive review of diet and cancer, the
      literature was primarily based on epidemiological studies, comparing dietary
      patterns between countries of low and high incidence for particular cancers. The
      American Institute for Cancer Research conducted an evidence-based review of the
      world literature and issued its first report in 1997, and the National Cancer
      Institute followed with evidence-based overviews of cancer prevention. The World
      Health Organization International Agency for Research on Cancer recently
      published a series of handbooks on cancer prevention in relation to dietary
      factors. The expert recommendations stemming from this extensive evidence
      subsequently influenced the clinical practice of medicine. In 2001, the complete
      sequencing of the human genome signified the beginning of the postgenomic era, in
      which new approaches and technologies are causing a shift in biomedical research.
      A widening understanding of the complex interactions among genotype, diet,
      lifestyle, and environment has evoked a change in clinical medical practice,
      where the evidence- and population-based protocol is evolving into a more
      personalized system that includes the analysis of individual genotype and
      phenotype. The implications of this evolution are considerable, because genomic
      medicine has the potential to give rise to personalized nutrition recommendations
      and specialized medical treatment.

PMID- 15570067
TI  - Diversity-oriented solid-phase synthesis and biological evaluation of
      oligonucleotide hairpins as HIV-1 RT RNase H inhibitors.
AB  - The inhibitory potencies of several hairpins comprising DNA, RNA and 2',5'-linked
      RNA segments were assessed against the RNase H activity of the human
      immunodeficiency virus reverse transcriptase (HIV-1 RT), an indispensable enzyme
      for HIV genomic replication. The hairpin library was constructed via diversity
      oriented nucleic-acid synthesis (DONAS), an approach inspired from traditional
      split-pool synthesis. DONAS provided access to an array of oligonucleotide
      hairpins possessing distinct conformational, structural and biological
      properties. The inhibitory potency of these compounds was highly specific towards
      HIV-1 RT RNase H and strongly depended on the structure of both the stem and
      tetraloop. Hairpins that have an overall A-type geometry are better inhibitors of
      RNase H activity than hairpins with 'intermediate' or B-type conformations,
      although interestingly, the inhibitory activity is quite sensitive to the
      nucleotide sequence in both the stem and loop regions of the hairpin. The most
      potent hairpins bear a 3',5'-linked rather than 2',5'-linked RNA loop, but the
      latter is necessary for activity of hairpins consisting of DNA stems. Inhibitory
      activity was essentially independent of hairpin thermal stability. The potent
      hairpins also demonstrated high nuclease resistance in biological media,
      particularly those bearing a 2',5'-linked tetraloop. These studies collectively
      bring into light a new class of nucleic acid aptamers that act exclusively upon
      the retroviral RNase H domain in vitro, and thus represent novel lead compounds
      for the development of specific and potent HIV-1 RT inhibitors.

PMID- 15570068
TI  - A novel nuclease-ATPase (Nar71) from archaea is part of a proposed thermophilic
      DNA repair system.
AB  - We have identified a novel structure-specific nuclease in highly fractionated
      extracts of the thermophilic archaeon Methanothermobacter thermautotrophicus
      (Mth). The 71 kDa protein product of open reading frame mth1090 is a nuclease
      with ATPase activity, which we call Nar71 (Nuclease-ATPase in Repair, 71 kDa).
      The nar71 gene is located in a gene neighbourhood proposed by genomics to encode
      a novel DNA repair system conserved in thermophiles. The biochemical
      characterization of Nar71 presented here is the first analysis from within this
      neighbourhood, and it supports the insight from genomics. Nuclease activity of
      Nar71 is specific for 3' flaps and flayed duplexes, targeting single-stranded DNA
      (ssDNA) regions. This activity requires Mg2+ or Mn2+ and is greatly reduced in
      ATP. In ATP, Nar71 displaces ssDNA, also with high specificity for 3' flap and
      flayed duplex DNA. Strand displacement is weak compared with nuclease activity,
      but in ATPS it is abolished, suggesting that Nar71 couples ATP hydrolysis to DNA
      strand separation. ATPase assays confirmed that Nar71 is stimulated by ssDNA,
      though not double-stranded DNA. Mutation of Lys-117 in Nar71 abolished ATPase and
      nuclease activity, and we describe a separation-of-function mutant (K68A) that
      has lost ATPase activity but retains nuclease activity. A model of possible Nar71
      function in DNA repair is presented.

PMID- 15570069
TI  - Cloning of CviPII nicking and modification system from chlorella virus NYs-1 and
      application of Nt.CviPII in random DNA amplification.
AB  - The cloning and expression of the CviPII DNA nicking and modification system
      encoded by chlorella virus NYs-1 is described. The system consists of a co-linear
      MTase encoding gene (cviPIIM) and a nicking endonuclease encoding gene (cviPIINt)
      separated by 12 nt. M.CviPII possesses eight conserved amino acid motifs (I to
      VIII) typical of C5 MTases, but, like another chlorella virus MTase M.CviJI,
      lacks conserved motifs IX and X. In addition to modification of the first
      cytosine in CCD (D = A, G or T) sequences, M.CviPII modifies both the first two
      cytosines in CCAA and CCCG sites as well. Nt.CviPII has significant amino acid
      sequence similarity to Type II restriction endonuclease CviJI that recognizes an
      overlapping sequence (RG--CY). Nt.CviPII was expressed in Escherichia coli with
      or without a His-tag in a host pre-modified by M.CviPII. Recombinant Nt.CviPII
      recognizes the DNA sequence CCD and cleaves the phosphodiester bond 5' of the
      first cytosine while the other strand of DNA at this site is not affected.
      Nt.CviPII displays site preferences with CCR (R = A or G) sites preferred over
      CCT sites. Nt.CviPII is active from 16 to 65 degrees C with a temperature optimum
      of 30-45 degrees C. Nt.CviPII can be used to generate single-stranded DNAs
      (ssDNAs) for isothermal strand-displacement amplification. Nt.CviPII was used in
      combination with Bst DNA polymerase I large fragment to rapidly amplify anonymous
      DNA from genomic DNA or from a single bacterial colony.

PMID- 15570070
TI  - Randomized phase III trial of marimastat versus placebo in patients with
      metastatic breast cancer who have responding or stable disease after first-line
      chemotherapy: Eastern Cooperative Oncology Group trial E2196.
AB  - PURPOSE: To determine whether a matrix metalloproteinase inhibitor improves
      progression-free survival (PFS) in patients with metastatic breast cancer who
      have responding or stable disease after first-line chemotherapy. PATIENTS AND
      METHODS: One hundred seventy-nine eligible patients were randomly assigned to
      receive oral marimastat (10 mg bid; n = 114) or a placebo (n = 65) within 3 to 6
      weeks of completing six to eight cycles of first-line doxorubicin- and/or taxane
      containing chemotherapy for metastatic disease. Patients were evaluated every 3
      months until disease progression. RESULTS: When comparing placebo with
      marimastat, there was no significant difference in PFS (median, 3.1 months v 4.7
      months, respectively; hazard ratio, 1.26; 95% CI, 0.91 to 1.74; P = .16) or
      overall survival (median, 26.6 months v 24.7 months, respectively; hazard ratio,
      1.03; 95% CI, 0.73 to 1.46; P = .86). Patients treated with marimastat were more
      likely to develop grade 2 or 3 musculoskeletal toxicity (MST), a known
      complication of the drug indicative of achieving a biologic effect, compared with
      patients administered placebo (63% v 22%, respectively; P < .0001). Patients with
      grade 2 or 3 MST had significantly inferior survival compared with patients who
      had grade 0 or 1 MST (median, 22.5 months v 28.2 months; P = .04). In addition,
      patients who had a marimastat plasma concentration of at least 10 ng/mL at month
      1 and/or 3 were significantly more likely to have grade 2 to 3 MST (P < .0001).
      CONCLUSION: Marimastat does not prolong PFS when used after first-line
      chemotherapy for metastatic breast cancer. Patients with higher marimastat levels
      exhibited MST, and MST was associated with inferior survival.

PMID- 15570071
TI  - Postmastectomy radiation improves local-regional control and survival for
      selected patients with locally advanced breast cancer treated with neoadjuvant
      chemotherapy and mastectomy.
AB  - PURPOSE: To evaluate the efficacy of radiation in patients treated with
      neoadjuvant chemotherapy and mastectomy. PATIENTS AND METHODS: We retrospectively
      analyzed the outcomes of 542 patients treated on six consecutive institutional
      prospective trials with neoadjuvant chemotherapy, mastectomy, and radiation.
      These data were compared to those of 134 patients who received similar treatment
      in these same trials but without radiation. RESULTS: Irradiated patients had a
      lower rate of local-regional recurrence (LRR) (10-year rates: 11% v 22%, P =
      .0001). Radiation reduced LRR for patients with clinical T3 or T4 tumors, stage >
      or = IIB disease (AJCC 1988), pathological tumor size >2 cm, or four or more
      positive nodes (P < or = .002 for all comparisons). Patients who presented with
      clinically advanced stage III or IV disease but subsequently achieved a
      pathological complete response to neoadjuvant chemotherapy still had a high rate
      of LRR, which was significantly reduced with radiation (10-year rates: 33% v 3%,
      P = .006). Radiation improved cause-specific survival (CSS) in the following
      subsets: stage > or = IIIB disease, clinical T4 tumors, and four or more positive
      nodes (P < or = .007 for all comparisons). On multivariate analyses of LRR and
      CSS, the hazard ratios for lack of radiation were 4.7 (95% CI, 2.7 to 8.1; P <
      .0001) and 2.0 (95% CI, 1.4 to 2.9; P < .0001), respectively. CONCLUSION: After
      neoadjuvant chemotherapy and mastectomy, comprehensive radiation was found to
      benefit both local control and survival for patients presenting with clinical T3
      tumors or stage III-IV (ipsilateral supraclavicular nodal) disease and for
      patients with four or more positive nodes. Radiation should be considered for
      these patients regardless of their response to initial chemotherapy.

PMID- 15570072
TI  - Racial disparity of epidermal growth factor receptor expression in prostate
      cancer.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) plays a critical role in
      prostate cancer (PC) signal transduction and is the target of a novel class of
      anticancer agents. Despite recent reports of interethnic variation in response to
      EGFR inhibitors, limited information exists regarding differences in expression
      of EGFR in PC patients. This has therapeutic relevance because a better
      understanding of the molecular basis underlying the ethnic variability will help
      in the design of individualized treatment regimens using EGFR inhibitors.
      PATIENTS AND METHODS: We investigated EGFR expression in a well-characterized
      cohort of PC patients to determine the association between EGFR expression and
      race. Tumor tissues from 202 radical prostatectomies performed between 1990 and
      2000 at the Veterans Administration Medical Center (New York, NY) were studied
      (142 African Americans, 60 whites; median age, 67 years; stage T2, n = 130; stage
      > or = T3, n = 72; Gleason score < 7, n = 110; Gleason score > or = 7, n = 92).
      Membrane-specific EGFR expression was evaluated immunohistochemically. RESULTS:
      EGFR overexpression, defined as complete membrane staining in more than 10% of
      tumor cells, was observed in 75 of 202 patients (37%). There was a significant
      association between EGFR overexpression and African American race (P = .0006),
      higher pretreatment prostate-specific antigen (PSA; P = .02), and stage (P =
      .02), but not Gleason score (P = .33). The association between African American
      race and EGFR overexpression remained significant in a multivariate model after
      controlling for grade, stage, and pretreatment PSA simultaneously (P = .003).
      CONCLUSION: Our data demonstrate that race contributes significantly to
      variability of EGFR expression in prostate cancer. Racial background may have an
      impact on the design of clinical trials to test the efficacy of anti-EGFR agents.

PMID- 15570073
TI  - Recruitment of patients into an internet-based clinical trials database: the
      experience of OncoLink and the National Colorectal Cancer Research Alliance.
AB  - PURPOSE: In March 2001, the National Colorectal Cancer Research Alliance (NCCRA)
      and OncoLink (http://www.oncolink.org) established a database to facilitate
      patient enrollment onto clinical trials. This study describes the population
      registering with the database and identifies discrepancies between individuals
      registering through the Internet and those registering through a telephone call
      center. METHODS: Participants registered with the NCCRA/OncoLink database through
      the Internet or a telephone call center. All participants entering the database
      completed a questionnaire regarding basic demographics, colon cancer risk
      factors, and indicated how they became aware of the database. Comparisons were
      made between individuals registering through the Internet and those registering
      through the telephone call center. RESULTS: A total of 2,162 participants
      registered during the first 16 months of the database. Most patients registered
      through the Internet rather than the telephone call center (88% v 12%; P < .001).
      More females than males registered (73% v 27%; P < .001). The majority (89%) were
      white. Participants registering through the Internet were younger than those
      registering through the call center (mean, 48.8 v 55.0 years; P < .001). There
      was no difference between the two groups with regard to sex or ethnicity.
      CONCLUSION: The Internet has the potential to increase the likelihood that
      interested individuals find appropriate clinical trials. Some of the
      discrepancies that are known to exist for access to the Internet were also seen
      for those registering with the database through the Internet. Despite these
      differences, the potential to increase clinical trial enrollment with this type
      of Internet-based database is high.

PMID- 15570074
TI  - Copy number of chromosome 17 but not HER2 amplification predicts clinical outcome
      of patients with pancreatic ductal adenocarcinoma.
AB  - PURPOSE: To determine the frequency and the potential clinical use of HER2
      (17q21) gene amplification and chromosome 17 aneuploidy in pancreatic ductal
      adenocarcinoma (PDAC). MATERIALS AND METHODS: Serial tissue sections of 50
      resected PDACs were analyzed with chromogenic in situ hybridization using locus
      specific HER2 probes and centromeric probes for chromosome 17. Centromeric probes
      for chromosome 7 and 8 were hybridized to confirm ploidy levels. Expression of
      HER2 protein was assessed by immunohistochemistry. Correlations of experimental
      findings with clinical and follow-up data were tested. RESULTS: The HER2 gene
      locus was frequently (24%) amplified in PDAC and the rate of overexpression (2+
      and 3+) was 10%, but no prognostic significance was found. Copy number analysis
      of chromosomes 7, 8, and 17 revealed disomic (40%), trisomic (36%), and
      hypertetrasomic (24%) tumors. Compared with patients with disomic tumors,
      patients with hypertetrasomic tumors exhibited a significantly decreased relapse
      free and overall survival (5.0 v 13.0 months, P = .0144 and 7.0 v 20.0 months, P
      = .0099, respectively). Multivariate analysis confirmed the independent
      prognostic significance of hypertetrasomy. CONCLUSION: Tumor ploidy levels
      correlate with prognosis of PDAC patients, indicating characteristic biologic
      properties of PDAC with high chromosomal instability. In contrast, no prognostic
      influence on patient outcome was found for the amplification of the HER2 oncogene
      or p185(HER2) overexpression. Therefore, evaluation of ploidy levels offers new
      opportunities for patient stratification in clinical trials and enables novel
      approaches to study the well-known aggressiveness of PDAC.

PMID- 15570075
TI  - Allele 2 of the interleukin-1 receptor antagonist gene is associated with early
      gastric cancer.
AB  - PURPOSE: In advanced gastric cancer (tumor stages T2-T4), associations with
      polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early
      stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa
      or submucosa (stage T1), the role of host genetic susceptibility remains to be
      determined. PATIENTS AND METHODS: Eighty-eight patients with early-stage gastric
      cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were
      genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis
      factor alpha (TNF-A) gene. Statistical analysis was performed using the chi2 test
      and the Fisher's exact test, respectively. RESULTS: The homozygous genotype IL
      1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer
      (P < .0001), whereas further associations with the IL-1 gene cluster were not
      observed. A weak association of the TNF-A-308A allele with the diffuse type of
      early-stage gastric cancer, and an association with a composite of two or three
      proinflammatory polymorphisms, which predispose to increased production of the
      proinflammatory cytokines IL-1beta and TNF-alpha, could also be demonstrated.
      CONCLUSION: The genotype IL-1RN*2/2 seems to be associated with early-stage
      gastric cancer. As opposed to advanced-stage gastric cancer, further
      proinflammatory cytokine polymorphisms were not associated independently, but
      might act in combination and mirror early steps of gastric carcinogenesis in
      hosts colonized by Helicobacter pylori. However, these findings await
      confirmation in future trials and should be underscored by gene expression
      studies.

PMID- 15570076
TI  - Randomized multicenter phase II trial of bolus plus infusional
      fluorouracil/leucovorin compared with fluorouracil/leucovorin plus oxaliplatin as
      third-line treatment of patients with advanced colorectal cancer.
AB  - PURPOSE: The addition of oxaliplatin to fluorouracil (FU) and leucovorin (LV)
      improves the outcome of patients with colorectal cancer (CRC). This multicenter
      study evaluated FU/LV with or without oxaliplatin in patients with metastatic CRC
      after disease progression on sequential fluoropyrimidine and irinotecan. PATIENTS
      AND METHODS: Two hundred fourteen patients were randomly assigned to receive LV
      200 mg/m2 intravenously (IV) and FU 400 mg/m2 IV bolus, followed by FU 600 mg/m2
      IV over 22 hours on days 1 and 2, every 2 weeks (LV5FU2); or LV and FU as
      described, plus oxaliplatin 85 mg/m2 IV over 2 hours on day 1 of the schedule
      (FOLFOX4). The primary end point was overall response. RESULTS: Baseline
      characteristics were similar in the two treatment arms. Objective response
      (complete + partial) rates for LV5FU2 versus FOLFOX4 were 2% v 13% (P = .0027),
      respectively. Median time to disease progression was 2.4 v 4.8 months (P <
      .0001), and median survival was 11.4 v 9.9 months (P = .20) for LV5FU2 and
      FOLFOX4, respectively. Among the 72 patients who crossed over from LV5FU2 to
      FOLFOX4, 6% responded. Symptomatic improvement was significantly better for
      patients in the FOLFOX4 arm (32% v 18% for LV5FU2, P = .05). Grade 3/4 toxicities
      for LV5FU2 and FOLFOX4 were neutropenia (13% and 42%, respectively), diarrhea (6%
      and 16%, respectively), and overall neuropathy (0% and 6%, respectively).
      CONCLUSION: In patients with metastatic CRC, the FOLFOX4 regimen was superior to
      LV5FU2 with a higher response rate and time to disease progression. FOLFOX4 is an
      effective regimen even after disease progression on two previous chemotherapy
      regimens with fluoropyrimidines and irinotecan.

PMID- 15570077
TI  - Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with
      locally advanced and metastatic pancreatic endocrine carcinomas.
AB  - PURPOSE: The role of systemic chemotherapy in the management of pancreatic
      endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable
      controversy. Response rates ranging from 6% to 69% have been reported for
      streptozocin-based chemotherapy. We retrospectively studied 84 patients with
      locally advanced or metastatic PEC who had been treated with fluorouracil,
      doxorubicin, and streptozocin (FAS) to determine the objective response rate,
      duration of progression-free survival (PFS), and duration of overall survival
      (OS). PATIENTS AND METHODS: Eligible patients had histologic or cytologic
      confirmation of their tumor and measurable disease on computed tomography or
      magnetic resonance imaging scans. Response to treatment was evaluated in this
      study using the new international criteria proposed by the Response Evaluation
      Criteria in Solid Tumors Committee. RESULTS: Sixty-one of the patients were male
      and 23 were female, with a median age of 54 years (range, 24 to 78 years). The
      response rate (RR) to FAS was 39%, with a median response duration of 9.3 months.
      The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver
      metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a
      worse OS (P < .0001 by log-rank test). Analyses showed that metastatic
      replacement of more than 75% of the liver and prior chemotherapy were
      independently associated with inferior PFS. CONCLUSION: Patients with locally
      advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and
      responders may experience longer PFS and OS. The volume of metastases in the
      liver is the most important predictor of outcome.

PMID- 15570078
TI  - Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does
      not correlate with EGFR expression in related metastatic sites: implications for
      treatment with EGFR-targeted monoclonal antibodies.
AB  - PURPOSE: We hypothesized that the detection of epidermal growth factor receptor
      (EGFR) expression performed in primary tumors for treatment with EGFR-targeted
      monoclonal antibodies could not always correlate with EGFR status in metastatic
      sites, thus making cancer cells in these sites resistant to therapy. The aim of
      our study was to correlate EGFR expression on primary tumors and related
      metastases in order to find out whether assessing EGFR status on primary cancer
      is to be considered an effective tool for planning treatment with EGFR-targeted
      antibodies. PATIENTS AND METHODS: We retrospectively evaluated EGFR
      immunohistochemistry from primary tumors and related metastatic sites in 99
      colorectal cancer patients. The site of primary tumor was colon in 77 patients
      (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84
      patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in
      five patients (5%). EGFR status was defined as positive if the percentage of
      malignant cells stained was > or = 1%. RESULTS: EGFR status was positive in 53
      primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the
      corresponding metastatic site was found negative, whereas it was found positive
      in seven metastases (15%) from EGFR-negative primary cancers. The difference
      between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR
      negative to EGFR-positive) was statistically significant (P = .036). CONCLUSION:
      Our results suggest that the detection of the EGFR in primary colorectal cancer
      could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies
      in a considerable proportion of both EGFR-positive and -negative primary tumors
      (36% and 15%, respectively).

PMID- 15570079
TI  - Second-line chemotherapy with irinotecan plus carmustine in glioblastoma
      recurrent or progressive after first-line temozolomide chemotherapy: a phase II
      study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).
AB  - PURPOSE: Glioblastoma multiforme (GBM), the most frequent brain tumor in adults,
      is not considered chemosensitive. Nevertheless, there is widespread use of first
      line chemotherapy, often with temozolomide, as a therapeutic option in patients
      with progressive disease after surgery and radiotherapy. However, at the time of
      second recurrence and/or progression, active and noncross-resistant chemotherapy
      regimens are required. The aim of the present multicenter phase II trial,
      therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and
      irinotecan chemotherapy. PATIENTS AND METHODS: Patients with histologically
      confirmed GBM, recurring or progressing after surgery, standard radiotherapy and
      a first-line temozolomide-based chemotherapy, were considered eligible. The
      primary end-point was progression-free survival at 6 months (PFS-6), and
      secondary end-points included response rate, toxicity, and survival. All patients
      were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU
      (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6
      weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the
      irinotecan dose was increased to 200 mg/m2. RESULTS: A total of 42 patients
      (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to
      90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median
      time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses
      (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable. CONCLUSION:
      The BCNU plus irinotecan regimen seems active and non-cross-resistant in patients
      with GBM with recurrence after temozolomide-based chemotherapy.

PMID- 15570080
TI  - European intergroup studies (MMT4-89 and MMT4-91) on childhood metastatic
      rhabdomyosarcoma: final results and analysis of prognostic factors.
AB  - PURPOSE: Final results are presented from two consecutive European studies for
      patients with metastatic rhabdomyosarcoma (RMS) to identify prognostic variables
      and determine the value of high-dose chemotherapy (HDCT) in complete remission.
      PATIENTS AND METHODS: A total of 174 patients aged 3 months to 18 years
      participated. From 1989 to 1991, patients received four cycles of intensive
      multiagent chemotherapy. From 1991 to 1995, patients achieving complete remission
      received consolidation with HDCT. All received local therapy (surgery, radiation
      therapy) according to response. RESULTS: At a median follow-up of 8 years, 5-year
      overall survival (OS) and event-free survival (EFS) for the whole group were 24%
      and 20%, respectively. No statistical difference was found between HDCT and
      standard chemotherapy (5-year OS, 36% v 27%; EFS 29% v 23%). Univariate analysis
      identified primary tumor in parameningeal, extremity, or other sites; age younger
      than 1 year and older than 10 years; bone or bone marrow metastases; multiple
      metastases; and multiple sites of metastases as unfavorable prognostic factors
      for OS and EFS. Multivariate analysis identified unfavorable site, bone or bone
      marrow involvement, and unfavorable age as independently unfavorable factors. Two
      subgroups were identified. Those with fewer than two unfavorable factors had 5
      year EFS and OS of 40% and 47%, respectively. Patients with > or = two
      unfavorable factors had 5-year EFS and OS of 7.5% and 9%, respectively.
      CONCLUSION: A minority of patients with metastatic RMS have better survival than
      overall results for this population suggest. Those in the highest risk group have
      such poor survival that they are candidates for first-line novel therapies. There
      is no evidence that consolidation with HDCT improves outcome.

PMID- 15570081
TI  - Short-term efficacy of methylphenidate: a randomized, double-blind, placebo
      controlled trial among survivors of childhood cancer.
AB  - PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant
      brain tumors (BTs) have a higher incidence of attention and learning problems in
      school than do their healthy peers. The present study tests the hypothesis that
      the psychostimulant methylphenidate (MPH) improves cognitive and social
      functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term
      survivors of ALL and BT identified as having attentional deficits on behavioral
      testing and parent or teacher report, and problems with academic achievement. The
      47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years)
      of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at
      participation. The patients (40 ALL, 43 BT) participated in a randomized, double
      blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg;
      maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg
      bid). The primary end points were weekly teacher and parent reports on the
      Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to
      placebo, significant improvement with MPH was reported by teachers and parents on
      the Conners' Rating Scales and by teachers on the Social Skills Rating System.
      However, no consistent advantage of moderate dose over low dose was observed. Of
      those participating, 66 (79.5%) of the 83 patients continued on best clinical
      management. CONCLUSION: Treatment with MPH can at least temporarily reduce some
      attentional and social deficits among survivors of childhood ALL and BT. Long
      term follow-up will reveal those subsets of patients who are more likely to
      benefit from MPH.

PMID- 15570082
TI  - Phase I study of the proteasome inhibitor bortezomib in pediatric patients with
      refractory solid tumors: a Children's Oncology Group study (ADVL0015).
AB  - PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicity (DLT),
      and pharmacodynamics of the proteasome inhibitor bortezomib (formerly PS-341) in
      children with recurrent or refractory solid tumors. PATIENTS AND METHODS: An
      intravenous bolus of bortezomib was administered twice weekly for 2 consecutive
      weeks at either 1.2 or 1.6 mg/m2/dose followed by a 1-week rest. The
      pharmacodynamics of bortezomib were evaluated by measurement of whole blood 20S
      proteasome activity. RESULTS: Fifteen patients, 11 assessable, were enrolled
      between November 2001 and February 2003. Dose-limiting thrombocytopenia, which
      prevented administration of a complete course (four doses in 2 weeks) of therapy,
      occurred in two of five assessable children enrolled at the 1.6 mg/m2 dose level.
      There were no other DLTs. Inhibition of 20S proteasome activity seemed to be dose
      dependent. The average inhibition 1 hour after drug administration on day 1 was
      67.2% +/- 7.6% at the 1.2 mg/m2/dose and 76.5% +/- 3.3% at the 1.6 mg/m2/dose.
      There were no objective antitumor responses. CONCLUSION: Bortezomib is well
      tolerated in children with recurrent or refractory solid tumors. The recommended
      phase II dose of bortezomib for children with solid tumors is 1.2 mg/m2/dose,
      administered as an intravenous bolus twice weekly for 2 weeks followed by a 1
      week break.

PMID- 15570083
TI  - Complementary and alternative medicine use by patients enrolled onto phase I
      clinical trials.
AB  - PURPOSE: To describe the prevalence, clinical characteristics, and pattern of use
      of complementary and alternative medicine (CAM) in patients enrolled onto phase I
      trials. PATIENTS AND METHODS: Questionnaires were administered to 108 patients
      with advanced malignancies enrolled onto phase I chemotherapy trials at the Mayo
      Clinic Comprehensive Cancer Center (Rochester, MN). CAM was classified into two
      modalities, pharmacologic and nonpharmacologic. Clinical and demographic data,
      including age, sex, and prior cancer treatment, were subsequently obtained from
      patient charts and examined for any correlation with CAM use, using chi2
      analysis. RESULTS: One hundred two survey forms were returned. Among respondents,
      88.2% (90 of 102) had used at least one CAM modality; 93.3% (84 of 90) and 53.3%
      (48 of 90) had used pharmacologic and nonpharmacologic CAM, respectively; and
      46.7% (42 of 90) used both modalities. Vitamin and mineral preparations
      constituted 89.3% (75 of 84) of all pharmacologic CAM used. Intake was highest
      for vitamins E (48.8% [41 of 84]) and C (38.1% [32 of 84]), and 71.4% (60 of 84)
      of respondents took nonvitamin/mineral agents. Green tea (29.8% [25 of 84]),
      echinacea (13.1% [11 of 84]), and essiac (9.5% [8 of 84]) were the most popular.
      Prayer and spiritual practices were the most commonly used nonpharmacologic CAM,
      accounting for 52.1% (25 of 48). Chiropractors, the most frequently visited
      nontraditional medicine practitioners, were consulted by only 10% (9 of 90) of
      those who practiced CAM. Both CAM modalities were used more frequently by women
      (53.5% [23 of 43]) than men (40.4% [19 of 47]). CONCLUSION: CAM use is common
      among patients in phase I trials and should be ascertained by investigators,
      because some of the agents used may interact with investigational agents and
      affect adverse effects and/or efficacy.

PMID- 15570084
TI  - Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with
      relapsed and refractory hematologic malignancies.
AB  - PURPOSE: Tipifarnib, an orally bioavailable inhibitor of farnesyl transferase,
      has activity in hematologic malignancies, but the dose required to achieve the
      proposed biologic end point, inhibition of farnesylation, is unknown. PATIENTS
      AND METHODS: The impact on post-translational farnesylation was assessed in 42
      patients with refractory hematologic malignancies and bone marrow involvement.
      Tipifarnib was taken orally for 21 days of a 28-day cycle. For cycle 1, patients
      were randomly assigned to one of four dose levels: 100 mg bid, 200 mg bid, 300 mg
      bid, and 600 mg bid. In cycle 1, peripheral blood and bone marrow mononuclear
      cells were analyzed for inhibition of HDJ2 prenylation by Western blot analysis
      at baseline and on day 21. RESULTS: Twenty-three patients were assessable for
      analysis of HDJ2 prenylation before and after therapy. Inhibition of
      farnesylation was noted at all dose levels, although the highest level of
      inhibition was noted at the 300-mg-bid dose. The inhibition of farnesylation in
      the peripheral blood correlated with the inhibition in the bone marrow (r =
      0.62). Of the 26 patients assessable for clinical activity after cycle 1, three
      patients had a significant decrease in total blasts count (acute myeloid leukemia
      in two patients, and chronic myelogenous leukemia in one patient). The inhibition
      of farnesylation was greater in the three responders than the nonresponders (P =
      .03). CONCLUSION: Farnesylation as measured by HDJ2 analysis was inhibited at all
      dose levels administered. Clinical activity may correlate with the degree of
      farnesylation inhibition, rather than dose of tipifarnib, and escalation beyond
      300 mg bid might not result in additional clinical activity.

PMID- 15570085
TI  - Diagnostic accuracy of the palliative prognostic score in hospitalized patients
      with advanced cancer.
AB  - PURPOSE: To evaluate the predictive accuracy of the Palliative Prognostic (PaP)
      score in patients with advanced cancer under the care of an oncologist. PATIENTS
      AND METHODS: The PaP score was calculated in 100 consecutive patients with
      advanced cancer hospitalized under the care of a medical or radiation oncologist
      at a university teaching hospital in Australia. The attending oncologist
      predicted the survival duration for the purpose of the scoring. The positive
      predictive value of the PaP score was evaluated. Survival analysis was performed
      to compare the survival of the three prognostic groups. RESULTS: Assessable
      survival data were available for 98 patients. The overall median survival was 12
      weeks (interquartile range, 7 to 25 weeks). The PaP score divided the
      heterogeneous patient sample into three isoprognostic groups related to the
      chance of surviving 1 month, with 64 patients in group A (> 70% chance), 32
      patients in group B (30% to 70% chance), and four patients in group C (< 30%
      chance). The estimated median survival of the three groups was 17 weeks (95% CI,
      12 to 26 weeks), 7 weeks (95% CI, 4 to 12 weeks), and less than 1 week (95% CI, <
      1 to 3 weeks), respectively. These survival differences were highly significant
      (log-rank test of trend, chi1(2) = 25.65; P < .0001). The 1-month survival of the
      groups was 97%, 59%, and 25%, respectively. CONCLUSION: When oncologists'
      survival estimates are used, the PaP score is able to identify accurately three
      isoprognostic patient groups, irrespective of the cancer type. The PaP score may
      help reduce the uncertainty of formulating a prognosis in patients with advanced
      cancer.

PMID- 15570086
TI  - Quality of life in patients with colorectal cancer 1 year after diagnosis
      compared with the general population: a population-based study.
AB  - PURPOSE: Quality of life (QOL) has become an important outcome measure for
      patients with cancer, but long-term results from population-based studies are
      rare. The objective of our study was to identify specific limitations of QOL in
      survivors of colorectal cancer in comparison with men and women from the general
      population 1 year after diagnosis when acute treatment effects are expected to
      have declined. PATIENTS AND METHODS: QOL was assessed 1 year after diagnosis in a
      population-based cohort of 439 patients with colorectal cancer from Saarland
      (Germany) using the EORTC-QLC30 questionnaire. Specific functional and symptom
      QOL scores were compared with published reference data from the general
      population. RESULTS: Of 439 patients, 378 of them survived the first year after
      tumor diagnosis (86.1%). Of these, 309 returned the questionnaire (response rate,
      81.7%). Compared with the general population, colorectal cancer patients scored
      their physical, role, cognitive, and global health functioning only slightly
      worse. More severe limitations were observed for the emotional and social
      functioning scales and for the symptom subscales of fatigue, dyspnea, insomnia,
      constipation, diarrhea, and financial difficulties. The differences regarding
      functional and symptom scores were predominantly found in younger age groups
      whereas older cancer patients and controls rated their health and QOL similarly.
      CONCLUSION: Deficits in emotional and social functioning and specific limitations
      like fatigue, dyspnea, insomnia, constipation, diarrhea, and financial
      difficulties are main factors hampering the QOL among colorectal cancer patients
      and seem to affect predominantly younger patients.

PMID- 15570087
TI  - Systematic review evaluating the timing of thoracic radiation therapy in combined
      modality therapy for limited-stage small-cell lung cancer.
AB  - PURPOSE: We employed meta-analytic techniques to evaluate early (E) versus late
      (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung
      cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation
      and chemotherapeutic regimen on timing. METHODS: Randomized trials published
      after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were
      included. Trials were analyzed by risk ratio (RR), risk difference, and number
      needed-to-treat methods. RESULTS: Overall survival (OS) RRs for all studies were
      1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92
      to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT
      versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis
      of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44
      (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2
      and 3 years, respectively, indicating a survival benefit of ERT versus LRT.
      Studies using once-daily fractionation showed no difference in 2- and 3-year OS
      RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS
      RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P =
      .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum
      based chemotherapy regimens had nonsignificant differences in OS. CONCLUSION: A
      small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was
      observed, similar to the benefit of adding RT to chemotherapy or prophylactic
      cranial irradiation. A greater difference was evident for hyperfractionated RT
      and platinum-based chemotherapy.

PMID- 15570088
TI  - Tissue collection for correlative studies in childhood cancer clinical trials:
      ethical considerations and special imperatives.
AB  - Federal regulations prescribe distinct protections for children participating in
      research studies. Procedures for collecting tissue specimens from children solely
      for research purposes must pose no more than a minor increase over minimum risk,
      thereby limiting the approvable correlative biologic studies to evaluate
      molecularly targeted agents in children with cancer. Ethical issues arise when
      approvable correlative studies are a mandatory component of an early-phase
      pediatric clinical trial of new anticancer agents. The National Cancer Institute
      Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue
      collection for correlative biologic studies in early-phase childhood cancer
      clinical studies of molecularly targeted agents. Workshop participants
      recommended the following: (1) tissue specimens for correlative studies should
      provide vital clinical and scientific results to qualify for early-phase
      pediatric study consideration; (2) parents should receive a realistic appraisal
      of the risks, requirements, and potential for benefit of phase I protocol
      participation; (3) investigators should clearly distinguish clinically necessary
      procedures from research procedures of no benefit to the child to improve
      correlative study informed consent; and (4) participation in correlative research
      studies included in clinical trials generally should be voluntary. The need to
      acquire important biologic data regarding new molecular agents will challenge the
      ingenuity of pediatric cancer researchers, necessitating the application of
      highly sensitive laboratory assay methods, new imaging procedures, and
      preclinical models of childhood cancer. Such innovative methods can allow
      necessary scientific information to be obtained while simultaneously respecting
      the protections appropriately afforded to children participating in research
      studies and minimizing the burden of research participation for children with
      cancer and their families.

PMID- 15570089
TI  - Case 1. Metastatic breast cancer presenting with panhypopituitarism.

PMID- 15570090
TI  - Case 2. Colon cancer presenting with intestinal intussusception.

PMID- 15570091
TI  - Case 3. Positron emission tomography-computed tomography diagnosis of metastatic
      melanoma with intussusception.

PMID- 15570092
TI  - Addressing spiritual care: calling for help.

PMID- 15570093
TI  - Get the facts straight.

PMID- 15570095
TI  - Delayed benefit of mammography screening in premenopausal women.

PMID- 15570096
TI  - Forensic DNA-typing technologies: a review.
AB  - Since the discovery of deoxyribonucleic acid (DNA) profiling in 1985, forensic
      genetics has experienced a continuous technical revolution, both in the type of
      DNA markers used and in the methodologies or its detection. Highly informative
      and robust DNA-typing systems have been developed that have proven to be very
      effective in the individualization of biological material of human origin. DNA
      analysis has become the standard method in forensic genetics used by laboratories
      for the majority of forensic genetic expertise and especially in criminal
      forensic casework (stain analysis and hairs) and identification.

PMID- 15570097
TI  - DNA extraction and quantitation of forensic samples using the phenol-chloroform
      method and real-time PCR.
AB  - Forensic laboratories are increasingly confronted with problematic samples from
      the scene of crime, containing only minute amounts of deoxyribonucleic acid
      (DNA), which may include polymerase chain reaction (PCR)-inhibiting substances.
      Efficient DNA extraction procedures, as well as accurate DNA quantification
      methods, are critical steps involved in the process of successful DNA analysis of
      such samples. The phenol-chloroform method is a sensitive method for the
      extraction of DNA from a wide variety of forensic samples, although it is known
      to be laborious compared with single-tube extraction methods. The relatively high
      DNA recovery and the quality of the extracted DNA speak for itself. For reliable
      and sensitive DNA quantitation, the application of real-time PCR is described. We
      modified a published real-time PCR assay, which allows for the combined analysis
      of nuclear and mitochondrial DNA, by introducing 1) improved hybridization probes
      with the use of minor groove binders; 2) an internal positive control (for both
      nuclear and mitochondrial DNA) for the detection of PCR inhibitors; and 3)
      different amplicon lengths for the determination of the degradation state of the
      DNA. The internal positive controls were constructed by site directed mutagenesis
      by overlap extension of the wild-type mitochondrial and nuclear DNA target with
      the advantage that no additional probes, which are cost-intensive, are required.
      The quantitation system is accomplished as a modular concept, which allows for
      the combined determination of the above-mentioned features (quantity/inhibition
      or quantity/degradation) depending on the situation.

PMID- 15570098
TI  - A real-time PCR protocol to determine the number of amelogenin (X-Y) gene copies
      from forensic DNA samples.
AB  - We present a fluorogenic real-time polymerase chain reaction (PCR) procedure to
      target a segment (106-112 base pairs [bp]) of the X-Y homologous amelogenin gene
      by measuring the 5' nuclease activity of the Taq deoxyribonucleic acid (DNA)
      polymerase using two (X-Fam-labeled and Y-Vic-labeled) specific Taqman MGB probes
      to enable simultaneous the detection of two specific PCR products (AMGY: 112-bp
      and AMGX: 106 bp) as they accumulate cycle by cycle during PCR. The method makes
      possible not only human nuclear DNA quantitation but also sex determination and
      has been applied to the analysis of low copy number DNA samples in forensic and
      ancient DNA studies. Specific quantification of human nuclear DNA is a
      recommended procedure in forensic casework as a way to adjust the DNA input on
      subsequent end-point PCR-based DNA typing approaches ensuring the optimal use of
      the limited amounts of nuclear DNA found in many forensic evidences. Nuclear DNA
      quantification also aids in the interpretation of the consistency of multiplex
      STR profiling data obtained from low copy number DNA samples.

PMID- 15570099
TI  - Species determination: the role and use of the cytochrome b gene.
AB  - Many large mammalian species are on the verge of extinction in part because of
      the trade in their skin, bone, horn, or body parts for supposed medicinal
      purposes. Identification of the species is required to determine that a crime has
      been committed. This chapter details a robust DNA technique using part of the
      cytochrome b gene on the mitochondrial genome that will work on poor-quality
      samples such as powdered horn. An appropriate deoxyribonucleic acid (DNA)
      extraction technique is required to obtain at least 10 ng of DNA. Amplification
      of part of the cytochrome b gene using universal primers produces a fragment of
      approx 486 bp in size. Direct sequencing of the PCR products allows comparison of
      the DNA sequence at this locus to those already described on the EMBL DNA
      database.

PMID- 15570100
TI  - Constructing STR multiplex assays.
AB  - Multiplex polymerase chain reaction (PCR) refers to the simultaneous
      amplification of multiple regions of deoxyribonucleic acid (DNA) using PCR.
      Commercial short tandem repeat (STR) assays that can coamplify as many as 16
      different loci have become widely used in forensic DNA typing. This chapter will
      focus on some of the aspects of constructing robust STR multiplex assays,
      including careful design and quality control of PCR primers. Examples from the
      development of a cat STR 12plex and a human Y chromosome STR 20plex are used to
      illustrate the importance of various parts of the protocol. Primer design
      parameters and Internet-accessible resources are discussed, as are solutions to
      problems with residual dye artifacts that result from impure primers.

PMID- 15570101
TI  - Y chromosome STR typing.
AB  - Because of their unique transmission properties and male specificity, markers
      located on the nonrecombining region of the Y chromosome (NRY) have become an
      important tool in forensic investigation. In the past few years, more than 50
      polymorphic Y chromosome-specific short tandem repeats (STRs) have been described
      and a set of 9 loci were selected, considered as the minimal haplotype included
      in the forensic databases, Y-STR Haplotype Reference Databases, the largest now
      available online (http://www.yhrd.org). Here, we describe a multiplex
      amplification strategy developed for ABI platforms to amplify the nine loci
      included in the minimal haplotype (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390,
      DYS391, DYS392, DYS393) as well as a second set of markers (DYS437, DYS438,
      DYS439, DYS460, DYS461, GATA A10, GATA C4, and GATA H4) used to improve the
      minimal haplotype diversity and, hence, the discrimination power. Together, these
      17 Y-STRs can be used to define highly discriminative haplotypes, providing a
      powerful tool in male lineage identification.

PMID- 15570102
TI  - Using online databases for developing SNP markers of forensic interest.
AB  - In this chapter we review and compare the online single nucleotide polymorphism
      databases that are now available as research tools. We give an outline of the
      search strategies that can be used to ensure the most appropriate loci for
      forensic applications are chosen.

PMID- 15570103
TI  - SNP typing in forensic genetics: a review.
AB  - Single nucleotide polymorphisms (SNPs) are emerging as new markers of interest to
      the forensic community because of their abundance in the human genome, their low
      mutation rate, the opportunity they present of analyzing smaller fragments of
      deoxyribonucleic acid (DNA) than with short tandem repeats--important in degraded
      DNA samples--and the possibility of automating the analysis with high-throughput
      technologies. Many new technologies for genotyping SNPs have been developed in
      the past few years. We describe the principles of the allelic discrimination
      reactions and the technologies used for each of them. The aim of this chapter is
      to help in the understanding of the methodologies used in SNP genotyping and in
      the selection of the most appropriate techniques for forensic purposes.

PMID- 15570104
TI  - Genotyping SNPs with the LightCycler.
AB  - Here, a single nucleotide polymorphism typing methodology is described based on
      polymerase chain reaction monitoring, in real time, of fluorescently labeled
      amplified products using the LightCycler. The main advantages of the system are
      the time required for the analysis (about 20 min), combined with the robustness,
      accuracy, and the sensitivity of the method.

PMID- 15570105
TI  - Universal tag arrays in forensic SNP analysis.
AB  - Microarray-based single nucleotide polymorphism (SNP) genotyping enables
      simultaneous and rapid detection of a large number of markers and is thus an
      attractive method for forensic individual acid identification. This assay relies
      on a one-color detection system and minisequencing in solution before
      hybridization to universal tag arrays. The minisequencing reaction is based on
      incorporation of a fluorescent dideoxynucleotide to a primer containing a tag
      sequence flanking the position to be interrogated. This one-color system detects
      C and T polymorphisms in separate reactions on multiple polymerase chain reaction
      targets with the fluorophore TAMRA coupled to the respective dideoxynucleotide.
      After incorporation, tagged primer sequences are hybridized through their
      complementary sequence on the array, and positive signals are detected by a
      confocal laser-scanner.

PMID- 15570106
TI  - SNP typing on the NanoChip electronic microarray.
AB  - We describe a single nucleotide polymorphism (SNP) typing protocol developed for
      the NanoChip electronic microarray. The NanoChip array consists of 100 electrodes
      covered by a thin hydrogel layer containing streptavidin. An electric currency
      can be applied to one, several, or all electrodes at the same time according to a
      loading protocol generated by the user. Biotinylated deoxyribonucleic acid (DNA)
      is directed to the pad(s) via the electronic field(s) and bound to streptavidin
      in the hydrogel layer. Subsequently, fluorescently labeled reporter oligos and a
      stabilizer oligo are hybridized to the bound DNA. Base stacking between the short
      reporter and the longer stabilizer oligo stabilizes the binding of a matching
      reporter, whereas the binding of a reporter carrying a mismatch in the SNP
      position will be relatively weak. Thermal stringency is applied to the NanoChip
      array according to a reader protocol generated by the user and the fluorescent
      label on the matching reporter is detected.

PMID- 15570107
TI  - Genotyping SNPs using a UV-photocleavable oligonucleotide in MALDI-TOF MS.
AB  - Matrix-assisted laser desorption time-of-flight mass spectrometry coupled with
      allele-specific primer extension is a proven method for typing single nucleotide
      polymorphisms (SNPs). A novel modification upon this methodology is the
      incorporation of a photocleavable linker within the extension primer. After
      completion of the primer extension reaction, photocleavage of the extension
      products results in two deoxyribonucleic acid (DNA) fragments of lower mass.
      Typically, the smaller cleavage product, which contains the genotyping
      information, is in the range of 1000-3000 Daltons. The decrease in primer mass
      allows for higher sensitivity in mass spectrometric measurement and increases the
      potential for higher levels of multiplexing. The disturbing mass spectrometric
      analysis peaks caused by salt adducts and doubly charged ions are diminished when
      analyzing lower-mass DNA fragments. Here, we illustrate the methodology for using
      photocleavable modified extension primers for detection of SNPs located on the Y
      chromosome. Genomic templates were prepared from anonymous male donors. Five
      regions of the Y chromosome containing the SNP markers M9, M42, M45, M89, and M96
      were amplified by polymerase chain reaction, treated with shrimp alkaline
      phosphatase, and subjected to primer extension reactions using primers containing
      a photocleavable building block at specific sites. After elongation, the
      extension primers were desalted and subjected to ultraviolet irradiation to
      cleave the products at the photocleavable site. Subsequently, the small fragments
      derived from the 3' ends of the molecules containing the genotype information
      were analyzed by matrix-assisted laser desorption ionization time-of-flight using
      a 3-hydroxypicolinic acid matrix.

PMID- 15570108
TI  - Mitochondrial D-loop and coding sequence analysis using pyrosequencing.
AB  - In forensic casework analysis, mitochondrial deoxyribonucleic acid (DNA) often is
      used when the evidence material contains scarce amounts of DNA. Here, a
      mitochondrial DNA typing system for D-loop and coding region analysis based on
      pyrosequencing is described. Pyrosequencing is a real-time, single-tube
      sequencing-by-synthesis method, in which a cascade of enzymatic reactions yields
      detectable light. This pyrosequencing system has a higher resolution than the D
      loop analysis performed routinely today as it also covers informative positions
      in the mitochondrial coding region. The system is composed of 16 polymerase chain
      reaction (PCR) fragments and 24 pyrosequencing reactions with a turn around time
      for a 96-well plate of less than 3 h after PCR.

PMID- 15570109
TI  - SNaPshot typing of mitochondrial DNA coding region variants.
AB  - We describe a rapid and robust assay to genotype mitochondrial deoxyribonucleic
      acid (mtDNA) coding region single nucleotide polymorphism (SNPs) using the
      SNaPshot (Applied Biosystems, Foster City, CA) minisequencing reaction kit. A
      protocol for mtDNA SNaPshot typing is described in detail, although we emphasize
      that this method allows great flexibility in the implementation of whatever set
      of mtDNA SNPs. We discuss the utility of our selection of mtDNA SNPs for
      molecular anthropologists and forensic geneticists. Firstly, these SNPs allow
      allocating common mitochondrial West Eurasian haplotypes into their corresponding
      branches of the mtDNA skeleton, with special attention to the subdivision of
      sequences belonging to haplogroup H, the most frequent European haplogroup (40
      50%) and the worst phylogenetically characterized in the first and second
      hypervariable segments (HVS-I/II; by far, the most common segments analyzed by
      sequencing). Second, the polymorphic positions selected for this multiplex
      reaction considerably increase the discrimination power of current mitochondrial
      analysis in the forensic field. The method shows high accuracy and robustness,
      avoiding both the use of alternative time-consuming classical strategies (i.e.,
      restriction fragment length polymorphism typing) and the requirement of high
      quantities of DNA template.

PMID- 15570110
TI  - Typing of Y chromosome SNPs with multiplex PCR methods.
AB  - We describe a method for the simultaneous typing of Y-chromosome single
      nucleotide polymorphism (SNP) markers by means of multiplex polymerase chain
      reaction (PCR) strategies that allow the detection of 35 Y chromosome SNPs on 25
      amplicons from 100 to 200 pg of chromosomal deoxyribonucleic acid (DNA).
      Multiplex PCR amplification of the DNA was performed with slight modifications of
      standard PCR conditions. Single-base extension (SBE) was performed using the
      SNaPshot kit containing fluorescently labeled ddNTPs. The extended primers were
      detected on an ABI 3100 sequencer. The most important factors for the creation of
      larger SNP typing PCR multiplexes include careful selection of primers for the
      primary amplification and the SBE reaction, use of DNA primers with homogenous
      composition, and balancing the primer concentrations for both the amplification
      and the SBE reactions.

PMID- 15570111
TI  - Y chromosome SNP analysis using the single-base extension: a hierarchical
      multiplex design.
AB  - Single nucleotide polymorphisms (SNPs) are the most frequent polymorphisms
      described in the human genome, and their analysis is becoming an extensive
      routine in molecular biology, not only in the forensic field, but also in
      population and clinical genetics. In particular, SNPs located on the Y chromosome
      have a specific utility as forensic tools, and based on this fact, we have
      designed a strategy that allows us to identify the most frequent haplogroups in
      European populations. We selected 29 markers among the 245 binary polymorphisms
      described in the Y-Chromosome Consortium tree. The whole set was grouped into
      four multiplexes in a hierarchical way, allowing us to determine the final
      haplogroup using only one or two multiplexes. In this way, we only type in the
      best-case nine SNPs, and in the worst possible combination 17 SNPs, to define the
      haplogroup. The selected strategy to type the SNPs was a single-base extension
      method using the SNaPshot multiplex kit from Applied Biosystems, and detailed
      practical procedures are described here. With this hierarchical strategy adapted
      for European populations the massive typing of SNPs was avoided, and therefore
      the time and money involved in the study was also reduced.

PMID- 15570112
TI  - SNaPshot for pharmacogenetics by minisequencing.
AB  - Genetic polymorphisms of genes coding for metabolic enzymes are helpful to
      predict how an individual may respond to medication or drugs. The described
      approach for the identification of genetic variations for the cytochrome P450
      enzymes CYP2D6 and CYP2C19 has been designed for the rapid genotyping of relevant
      alleles (CYP2D6*1, -*3, -*4, -*6, -*7, and -*8 and CYP2C19*1, -*2, -*3, -*4, and 
      *5) by performing polymerase chain reaction amplifications of genomic regions
      containing the SNP followed by a single-tube multiplex single base extension
      (minisquencing) reaction. This multiplex assay can easily be expanded for
      additional genes and single nucleotide polymorphisms (SNPs). Minisequencing is a
      sensitive, reproducible, and time-saving method for SNP typing that can be
      performed using ordinary laboratory equipment.

PMID- 15570113
TI  - Methods for the study of ancient DNA.
AB  - Whereas the analysis of ancient DNA (aDNA) has become an increasingly popular
      mode of investigation in both archaeological and evolutionary studies, this
      approach is complicated by the degraded nature of ancient nucleic acids, the
      presence of enzymatic inhibitors in aDNA extracts, as well as the risk of
      contamination during either excavation or manipulation of samples. Despite these
      difficulties, numerous methods have been developed to optimize the recovery,
      study, and authentication of aDNA. In this article, we describe the procedures
      used in our laboratory to extract and amplify informative DNA segments from
      prehistoric or protohistoric human samples, as well as the precautions and
      strategies implemented to avoid or at least detect contaminations.

PMID- 15570114
TI  - Protocols for ancient DNA typing.
AB  - Molecular analysis of fossil and archaeological remains has been established as a
      powerful tool in providing new insight in phylogenetic investigations. The
      overlapping set of molecular modifications and degradation that forensic samples
      share with archaeological specimen suggests the application of similar technical
      approaches to the respective biological material. Polymerase chain reaction is
      the molecular technique of choice for the retrieval of specimen deoxyribonucleic
      acid (DNA) molecules. Because of intrinsic sensitivity, potential contaminations
      from exogenous DNA sources must be monitored through the entire process by the
      introduction of multiple blank controls. Cloning and sequencing of polymerase
      chain reaction products often is the only way to discriminate between
      contaminations and endogenous sequences as well as to identify variable positions
      from nucleotide modifications/DNA polymerase errors. Phylogenetic analysis and
      investigations of the pattern of substitutions are an additional and necessary
      step to validate the retrieved sequence. Comparison with available related
      samples (modern or extinct) is critical to correctly validate the results and to
      avoid artifactual data.

PMID- 15570116
TI  - Clinical presentation and anatomic position of L3-L4 disc herniation: a
      prospective and comparative study.
AB  - OBJECTIVE: A prospective, controlled cohort study was conducted to assess the
      anatomic transverse location and clinical presentation of L3-L4 disc herniation
      compared with lower lumbar levels. METHODS: This study prospectively identified
      37 patients diagnosed with L3-L4 disc herniation (study group) and 52 patients
      diagnosed with L4-L5 and L5-S1 herniation (control group). The following clinical
      data were collected: age, femoral stretch test, motor strength, sensation, and
      deep tendon reflexes. The anatomic transverse location of the disc fragments was
      assessed by computed tomography or magnetic resonance imaging and was classified
      as either central, posterolateral, foraminal, or far lateral. RESULTS: The
      patients in the study group were older than the patients in the control group,
      and neurologic deficit was more common. The transverse location was foraminal and
      extraforaminal in 59% of the study group compared with 27% of the control group.
      These differences were statistically significant. CONCLUSIONS: The incidence of
      foraminal and far lateral disc herniation is significantly higher at the L3-L4
      level compared with lower lumbar levels. When examining an older patient
      complaining of thigh pain, special attention should be given to the quadriceps
      strength, patellar reflex, and femoral stretch test. The L3-L4 foraminal and
      extraforaminal area should be assessed carefully.

PMID- 15570117
TI  - Variability of somatosensory evoked potential monitoring during scoliosis
      surgery.
AB  - OBJECTIVE: Somatosensory evoked potentials (SEPs) of 65 patients undergoing
      scoliosis surgery were monitored by stimulation of posterior tibial nerve to
      observe variations in latencies and amplitudes. METHODS: Monitoring was divided
      into five stages: pre incision, spine exposure, instrumentation loading,
      deformity correction, and wound closure (stages 1-5, respectively). RESULTS: We
      found the latency showed significant increase and the amplitude significant
      reduction from stages 1 to 2. There was no significant variability from stages 2,
      3, and 4, but both latency and amplitude recovered significantly from stage 4 to
      5. This variability correlated with the changes in mean arterial pressure and end
      tidal concentrations of isoflurane and was not dependent on the type of surgical
      procedure. If either 50% amplitude reduction or 10% latency prolongation of SEP
      compared with baseline recordings at stage 1 (pre incision) was used as warning
      criterion, the overall false-positive rate was 23.1%. It was significantly
      reduced to 7.7% if stage 2 (spine exposure) recordings were used as the baseline
      (P < 0.05). The false-positive rate decreased to 0% if a combined 50% amplitude
      reduction and 10% latency prolongation of SEP compared with the stage 2 baseline
      were used (P < 0.001). CONCLUSION: Based on these findings, we concluded that the
      time to obtain SEP baseline data should be adjusted to be post incision instead
      of pre incision.

PMID- 15570118
TI  - Pediatric spine fractures: a review of 137 hospital admissions.
AB  - OBJECTIVE: The anatomy and biomechanics of the growing spine produce failure
      patterns different from those in adults. Spinal injury in the pediatric patient
      is a concern as prevention of further neurologic damage and deformity and the
      good potential for recovery make timely identification and appropriate treatment
      of such injury critical. A retrospective clinical case series was conducted to
      present data from a large series of pediatric patients with spine injuries from a
      single regional trauma center. METHODS: One hundred thirty-seven children with
      spine injuries were seen over 10 years and were divided into three age groups: 0
      9, 10-14, and 15-17 years. Analysis of variance and chi2 were used to analyze
      differences between groups. RESULTS: There were 36 patients aged 0-9, 49 aged 10
      14, and 52 aged 15-17. Spine injury incidence increased with age. Motor vehicular
      accidents were the most common cause in this series. There were 36% cervical, 34%
      thoracic, 29% lumbar, 34% multilevel contiguous, and 7% multilevel noncontiguous
      involvement. Nineteen percent had spinal cord injury. Thirteen of 21 complete
      neurologic injuries and all 3 incomplete injuries improved. Cord injury was more
      common in the 0-9 age group. Four of five patients with spinal cord injury
      without radiographic abnormality (SCIWORA) were in the 0-9 age group and had
      complete neurologic injuries. Young children with cervical injuries were more
      likely to die than older children. Fifty-three percent had associated injuries.
      Eighteen percent underwent decompression, fusion, and instrumentation. Two
      patients developed scoliosis. The complication rate in surgical patients was
      higher than in patients treated nonsurgically and in polytrauma patients. This
      may be related to the severity of the initial injury. CONCLUSIONS: Our results
      suggest age-related patterns of injury that differ from previous work. The
      incidence of cord injury is 20% with higher frequencies in the young child.
      Potential for neurologic recovery is good. Young children have a higher risk for
      death than older children. There was no predominance of cervical injuries in the
      young child. The incidence of SCIWORA was low. Higher complication rates were
      seen in polytrauma and surgical patients.

PMID- 15570119
TI  - Whole-spine magnetic resonance imaging in patients with neurofibromatosis type 1
      and spinal deformity.
AB  - OBJECTIVE: Whole-spine magnetic resonance imaging (MRI) has been recommended in
      the preoperative evaluation of patients with neurofibromatosis type 1 (NF-1).
      However, no large study has identified the role of MRI in the classification and
      management of this condition. A retrospective study of 27 patients with NF-1,
      presenting with spinal deformity, who were investigated with plain radiographs
      and whole-spine MRI, was conducted to determine the role of whole-spine MRI in
      the classification and management of patients with NF-1 and spinal deformity.
      METHODS: The medical records, radiographs, and MRI studies of 27 neurologically
      intact patients with NF-1 and spinal deformity, who had been followed for a
      minimum of 2 years, were reviewed. RESULTS: The study group comprised 27
      patients, 11 of whom were categorized as having nondystrophic and 16 as having
      dystrophic curves based on radiographic features. All patients had normal
      neurologic function. In the nondystrophic group, MRI identified dystrophic
      changes in four patients (associated with a high rate of curve progression in
      one). A high incidence of intraspinal and paraspinal neurofibromas was documented
      (overall 37%) in both nondystrophic and dystrophic groups. Significantly more
      tumors were identified adjacent to the convexity of the curve in the dystrophic
      group. CONCLUSION: In a mixed population of pediatric and adult patients with NF
      1, normal neurologic function, and spinal deformity, MRI of the whole spine
      proved useful in the identification of occult vertebral dysplasia and in
      demonstration of intraspinal and paraspinal neoplasms.

PMID- 15570120
TI  - Evaluation of a novel pedicle probe for the placement of thoracic and lumbosacral
      pedicle screws.
AB  - BACKGROUND: Pedicle screw instrumentation is common in the lumbar spine and is
      gaining acceptance in the thoracic spine. The pedicle is generally cannulated
      with a gearshift probe or curette. SafePath (Mekanika, Boca Raton, FL) is an
      alternative pedicle probe designed for pedicle cannulation. This is a blunt
      tipped, nonaggressive drill that seeks the cancellous portion of the pedicle.
      OBJECTIVE: The objective of this study was to evaluate the accuracy of this
      device in comparison with techniques commonly used for pedicle cannulation.
      METHODS: Four osteoligamentous fresh-frozen thoracic to sacral cadaveric spines
      were studied. The pedicles of one side of each cadaver were cannulated with the
      SafePath device. The contralateral pedicles were cannulated with either a
      gearshift probe or a 3-0 cervical curette. The accuracy of pedicle probe
      placement was evaluated by radiography, computed tomography (CT) scan, and direct
      observation via dissection. RESULTS: By direct observation, 51 of 128 pedicles
      were violated (40%). There were not significant differences between the results
      obtained with the gearshift probe or curette; there were 2 of 22 lumbosacral
      violations (9%) and 14 of 45 thoracic violations (33%). With the SafePath device,
      there were 0 of 22 lumbosacral violations (0%) and 34 of 45 thoracic violations
      (76%). SafePath performed significantly better in the lumbar spine and
      significantly worse in the thoracic spine. The accuracy for determining pedicle
      violation was 88% for radiography and 85% for CT. CONCLUSIONS: The results of
      this in vitro study suggest that the SafePath device may represent an alternative
      to traditional pedicle cannulation techniques in the lumbosacral spine. However,
      the opposite is true in the thoracic spine, where SafePath performed
      significantly worse than traditional techniques.

PMID- 15570121
TI  - Effect of decortication on laminar strength during sublaminar wiring: an
      experimental study.
AB  - Eighty lumbar segments from 16 female sheep were used to investigate the effect
      of laminar decortication on the strength of the lamina during sublaminar wiring
      procedure. Sheep were 12-14 months old. Forty vertebrae from eight animals were
      decorticated before loading with sublaminar wire to failure, and 40 vertebrae
      from the remaining eight sheep were tested with the same procedure but intact.
      The effects of bone mineral density (BMD) and laminar dimensions on laminar
      strength in both decorticated and nondecorticated groups were also investigated.
      The failure force values of the laminae for decorticated and nondecorticated
      groups were 881.15 +/- 36.86 and 298.48 +/- 21.99 N, respectively (P < 0.001).
      There was a positive linear relationship between BMD and laminar strength in an
      intact lamina. In a decorticated lamina, no significant relationship existed
      between these variables. There was a negative linear relationship between
      mediolateral length of hemilamina and laminar strength in both intact and
      decorticated vertebra. Laminar strength after decortication was positively
      related to dorsoventral length of the remaining portion of the lamina.
      Decortication leads to a statistically significant decrease in laminar strength.

PMID- 15570122
TI  - Radiographic and functional outcome after surgical management of severe scoliosis
      in skeletally immature patients with muscular dystrophy.
AB  - OBJECTIVE: Most patients with muscular dystrophy (MD) develop progressive
      scoliosis after losing ambulatory status, but some cases develop severe scoliosis
      at a skeletally immature age before losing ambulatory status. Only a few studies
      have been conducted in skeletally immature patients with severe scoliosis. The
      purpose of this study was to assess the functional and cosmetic outcome in
      skeletally immature patients with severe scoliosis. METHODS: Preoperative,
      immediate postoperative, and final follow-up radiographs were analyzed in 10
      consecutive skeletally immature patients with respect to the Cobb angle degree
      and the pelvic obliquity angle correction, how long the correction was
      maintained, and the development of the crankshaft phenomenon. In the functional
      assessment, the ability to sit balanced, according to the Mulcahy method, and the
      ability to use hands, according to the Rhyu method, were evaluated. Furthermore,
      the degree of subjective satisfaction was evaluated in these patients. RESULTS:
      The average age of the patients was 10.4 years, and the average follow-up period
      was 33 months with minimum 2 years' follow-up. All 10 patients survived and were
      available at the follow-up. The mean Cobb and pelvic obliquity angles were 80
      degrees and 17 degrees at the time of the surgery, 31 degrees and 3.7 degrees
      immediately after the surgery, and 35 degrees and 4.7 degrees at the time of the
      final follow-up, respectively. The initial mean Cobb angle correction averaged
      61%, with 78% of pelvic obliquity corrected. These corrections were maintained
      over time in most cases. At the time of the surgery, the mean volume of blood
      loss was 1111 mL, with an average operation time of 411 minutes. There were no
      major complications. At the time of the last follow-up, no patient showed
      development of the crankshaft phenomenon. The average score for the ability to
      sit balanced improved from 4.4 to 6.6 according to the Mulcahy evaluation method.
      The scores for hand use were 2.2-2.7. However, the forced vital capacity of the
      lungs decreased from a preoperative 48% to 46.1%. CONCLUSIONS: These results
      indicate that even in very young MD patients with severe scoliosis, acceptable
      curve correction can be achieved and maintained with surgery. The improved pelvic
      obliquity and scoliosis angle stabilized the spine, freeing the upper extremities
      and allowing productive activities characteristic of childhood.

PMID- 15570123
TI  - Operative treatment for coccygodynia.
AB  - OBJECTIVE: Few data exist comparing the surgical and nonsurgical treatment of
      coccygodynia. We sought to retrospectively review our experience with
      coccygectomy compared with injections for the relief of coccygodynia to determine
      rates of success and patient satisfaction and identify complications. METHODS:
      From March 1993 to January 2002, 51 consecutive patients with the diagnosis of
      coccygodynia were evaluated. All of the patients complained of pain while sitting
      and had localized pain to external and internal palpation of the coccyx on
      physical examination. Nonoperative treatment (medications, cushions, therapy) had
      failed to relieve the patients' symptoms. All patients were seen in follow-up for
      physical examination and completed a questionnaire by an independent examiner.
      Follow-up of the patients was 26 months (range 12-59 months). Follow-up data were
      available on 45 of the 51 enrolled. The patients were divided as follows: 20
      patients were treated with total coccygectomy and 25 patients were treated with
      injection therapy. RESULTS: Of those treated operatively, 18 patients (90%) felt
      improved and were satisfied with the procedure. Two patients felt their symptoms
      to be unchanged and were dissatisfied. Postoperative complications included seven
      wound problems: four superficial infections and three patients with persistent
      drainage. All resolved with local wound care and oral antibiotics. No further
      surgery was necessary. There were no bowel injuries and no reports of sphincter
      problems. Of those treated with injections, 5 of the 25 (20%) felt improvement
      and were satisfied. Sixteen (64%) were not improved, and four (16%) felt worse.
      Five (20%) eventually were treated with coccygectomy, four with satisfactory
      relief in symptoms. CONCLUSIONS: Despite the potential for wound problems,
      coccygectomy for relief of coccygodynia can be a safe and effective treatment
      option with a high patient satisfaction rate. Wound closure and postoperative
      wound care are of utmost importance.

PMID- 15570124
TI  - Surgical treatment of intramedullary spinal cord ependymomas: can outcome be
      predicted by tumor parameters?
AB  - OBJECTIVE: The aim of this study was to investigate whether the tumor parameters
      of spinal intramedullary ependymomas are significant predictors of clinical
      presentation and postsurgical outcome. METHODS: The study involved 21 cases of
      intramedullary ependymoma that were operated on between 1988 and 2001. The
      patients were 13 males (62%) and 8 females (38%), with an age range of 9-70 years
      (median 38 years). RESULTS: In most cases (13; 62%), preoperative neurologic
      examination revealed a sensorimotor deficit in at least one limb. Complete tumor
      removal was achieved in all cases. The patients with wider tumors had poorer
      preoperative neurologic condition and poorer neurologic outcome. Tumor length
      (equivalent to myelotomy length) was not correlated with preoperative neurologic
      status, but longer length was significantly associated with development of
      dysesthesia post surgery. In contrast to tumor length, tumor/cord ratio (ratio of
      the tumor width to the largest cord width at the tumor site) was identified as a
      significant predictor of preoperative neurologic status and outcome. Ratio values
      of >0.80 were correlated with poorer preoperative clinical status and poorer
      neurologic outcome. Neither extent of edema (determined from length [in
      millimeters] of hyperintensity on T2-weighted images) nor presence of a cyst in
      the tumor was significant relative to postoperative neurologic recovery in these
      cases. CONCLUSIONS: This study demonstrated that the width of the tumor relative
      to the cord is the main predictor of neurologic presentation and postoperative
      status. The length of the tumor affects the postoperative dysesthesia
      development.

PMID- 15570125
TI  - Lumbar sympathectomy increases blood flow in a dog model of chronic cauda equina
      compression.
AB  - OBJECTIVE: This study was designed to assess changes in blood flow of the dog
      cauda equina after lumbar sympathectomy using an experimental chronic cauda
      compression model. METHODS: The cauda equina was compressed at 10 mm Hg with a
      plastic balloon in all animals (n = 12). One week later, bilateral lumbar
      sympathectomy was carried out in the LSX group (n = 7), and vessels of the cauda
      equina were thereafter observed for 90 minutes using a specially designed
      microscope supplied with a video camera. Five animals did not undergo
      sympathectomy and were used as controls. The volume of blood flow was calculated
      from two parameters: velocity (mm/s) and diameter (microm) of a vessel observed
      in each animal. RESULTS: The increment in vessel diameter in the LSX group was
      pronounced at 30 and 45 minutes after sympathectomy compared with the control
      group (P < 0.05). Blood flow in the LSX group was increased at 30 minutes
      depending on dilation of the vessel diameter compared with the control group (P <
      0.05). The velocity in the observed vessels remained unchanged throughout the
      measurements. CONCLUSIONS: These data suggest that lumbar sympathectomy could
      induce an increase in blood flow of the compressed cauda equina. As lumbar
      sympathetic block increases blood flow not only in the lower limbs but also in
      the cauda equina, it might be evaluated for a conservative treatment of
      intermittent claudication due to lumbar spinal canal stenosis.

PMID- 15570126
TI  - Late stress fracture of a well-incorporated autologous fibula strut graft in the
      cervical spine: a case report.
AB  - Four-level corpectomy for cervical spondylotic myelopathy presents special
      challenges to successful outcomes. At our institution, where the senior author
      has performed over 300 multilevel corpectomies with autologous fibula
      reconstruction, only 11 four-level procedures have been performed. It is
      important to consider the length of time required for complete revascularization
      of these long strut grafts as well as unusual postural or gait biomechanics the
      patient may have. Patients with altered gait or trunk stability who require
      anterior surgery for cervical spondylotic myelopathy may be best served by
      concurrent posterior fusion. We report a case in which a patient with cervical
      spondylotic myelopathy and diplegic cerebral palsy developed a stress fracture in
      the midportion of his well-incorporated autologous fibula strut graft 1 year
      after it was placed following four-level corpectomy.

PMID- 15570127
TI  - Dropped head syndrome associated with cervical spondylotic myelopathy.
AB  - We report a case of an 80-year-old woman with dropped head syndrome associated
      with cervical spondylotic myelopathy. She could not keep her cervical spine in a
      neutral position for >1 minute. She had a disturbed gait and severe kyphotic
      deformity in her thoracic spine. Magnetic resonance imaging revealed severe
      compression of the spinal cord due to cervical spondylotic change. Laminoplasty
      from C2 through C6 levels was performed. One year after operation, she could keep
      her cervical spine in a neutral position easily. Her gait was also improved. The
      symptoms did not recur during 4 years of follow-up. We surmise that to maintain
      daily activities, she had to extend her cervical spine owing to the thoracic
      kyphotic deformity, resulting in compression of the spinal cord. The compression
      led to weakening of the cervical extensor muscles. Cervical laminoplasty was
      effective.

PMID- 15570128
TI  - Synovial cyst at the C1-C2 junction in a patient with atlantoaxial subluxation.
AB  - Synovial cysts of the cervical spine causing myelopathy are rare. The
      pathogenesis of these cysts is often attributed to degenerative changes of the
      facet joints or microtrauma. The authors report a synovial cyst at the C1-C2
      junction in a patient with atlantoaxial subluxation without a congenital anomaly
      or inflammatory conditions. A 72-year-old man presented with a progressive right
      sided myelopathy attributed to a C1-C2 synovial cyst accompanied by atlantoaxial
      subluxation and C3-C6 spondylosis. Magnetic resonance imaging of the cervical
      spine showed a large cystic mass compressing the spinal cord located at the C1-C2
      junction. A C1 hemilaminectomy, complete evacuation of the cyst contents, and
      posterior atlantoaxial fusion were performed, and a double-door laminoplasty was
      also done at C3-C6. The patient showed significant improvement of paresthesia and
      motor weakness of the right upper and lower extremities immediately after the
      operation. Synovial cysts should be considered in the differential diagnosis of
      an extradural mass of the upper cervical spine. Posterior fusion combined with
      direct excision of the cyst may be the optimum treatment of a synovial cyst at
      the C1-C2 junction in a patient with atlantoaxial subluxation.

PMID- 15570129
TI  - Asymptomatic massive dural ectasia associated with neurofibromatosis type 1
      threatening spinal column support: treatment by anterior vascularized fibula
      graft.
AB  - We report the case of a girl with a dystrophic neurofibromatosis lumbar scoliosis
      with asymptomatic progression and spread of dystrophic characteristics over 18
      years. Resorption of almost the entire anterior column of L1-L4 had occurred
      despite a previous posterior instrumentation and fusion. A vascularized fibula
      bone graft wrapped in titanium mesh was used as an anterior structural graft.
      With close follow-up, the need for this type of salvage surgery might have been
      averted. Further follow-up showed no graft resorption and unchanged sagittal
      alignment after 3 years.

PMID- 15570130
TI  - Anterior stabilization of the upper thoracic spine via an "interaortocaval
      subinnominate window": case report and description of operative technique.
AB  - Because of the limitations imposed by the thoracic cage and the paravertebral
      structures, anterior access to T3 remains a challenge, particularly for the
      application of anterior fixation devices. Specifically, the appropriate
      trajectory for the correct placement of T3 screws requires significant caudal
      access; this may necessitate the addition of a high-level thoracotomy to the
      traditional combined neck exposure/sternotomy approach to the cervicothoracic
      junction (ie, the "trap door" exposure). The authors describe a technique for the
      placement of the T3 screws of a T1-T3 spinal titanium alloy plate via an
      "interaortocaval subinnominate window" in a patient who underwent a T2
      vertebrectomy and polymethylmethacrylate reconstruction. The case history,
      imaging studies, illustrations, and intraoperative photographs are presented.
      This novel technique allows for the optimal placement of anterior fixation
      devices in the upper thoracic spine without the need to extend the caudal
      exposure with an anterolateral thoracotomy.

PMID- 15570131
TI  - Superior mesenteric artery syndrome following correction of kyphosis in an adult.
AB  - Superior mesenteric artery (SMA) syndrome is well described in the pediatric
      literature; however, to date, it has not been described in an adult individual
      undergoing correction of thoracic kyphosis. Medical history, physical findings,
      and the results of imaging studies were analyzed to describe the patient's onset
      of gastrointestinal obstruction following surgical correction of thoracic
      kyphosis. The postoperative course was marked by the onset of nausea and vomiting
      on postoperative day 24. The patient was admitted to the hospital, and the small
      bowel follow-through study showed blockage of the third portion of the duodenum
      at the level of the SMA. Oral intake was restricted, and total parenteral
      nutrition was instituted with complete resolution of her symptoms. At 1 year
      postoperatively, the patient was symptom-free. Although vascular compression of
      the duodenum with subsequent nausea and vomiting and electrolyte imbalance,
      caused by the relative lengthening of the spine, is most commonly associated with
      surgical correction of coronal plane deformities (ie, scoliosis), it may occur in
      patients undergoing correction of thoracic kyphosis as well. SMA syndrome is a
      well known potential complication in adolescents, and it should also be taken
      into consideration in adults undergoing deformity correction. Early institution
      of general medical measures of nasogastric suction, oral intake restriction, and
      intravenous alimentation can be successful.

PMID- 15570132
TI  - Percutaneous vertebroplasty in vertebra plana secondary to metastasis.
AB  - Severe vertebral body collapse secondary to metastatic disease is considered a
      contraindication to vertebroplasty by most authors. Resolution of radicular pain
      after vertebroplasty is also not well reported. A case of successful
      vertebroplasty of a severe T7 collapse secondary to metastatic thymic carcinoma
      with an associated posterior cortical fracture of the body that resulted in
      resolution of axial and radicular pain is described. The patient had near
      complete relief of severe axial and radicular pain. Postoperative imaging
      revealed anterior placement of the cement without leak into the spinal canal or
      the intervertebral foramen. The objectives are to describe the clinical and
      radiographic features of the case to support the idea that vertebra plana
      secondary to metastatic disease may not be a contraindication to vertebroplasty
      in selected patients. Simple techniques to avoid leak of cement into the spinal
      canal are also described. Severe vertebral collapse secondary to metastatic
      fractures may not be a contraindication to vertebroplasty, provided that
      appropriate measures are taken to place the trocars and to avoid extrusion of
      cement into the spinal canal.

PMID- 15570133
TI  - Effect of high-volume and -intensity endurance training in heart transplant
      recipients.
AB  - BACKGROUND: A recommended component of heart transplant recipients (HTR) is
      endurance-oriented exercise therapy. However, the trainability of HTR after
      transplantation is vague. We examined the effect of high-volume and -intensity
      exercise training on exercise performance in HTR, compared with HTR undergoing
      regular rehabilitation training, and sedentary healthy subjects (SHS). METHODS:
      We studied four groups of individuals; of those, three groups were HTR. Subjects
      were a regularly trained HTR group of denervated (HTR-D; N = 15), reinnervated
      (HTR-R; N = 26) hearts, a high-volume and -intensity endurance-training group
      (training time 7-20 h.wk(-1); HTR-ET; N = 12), and a group of sedentary healthy
      subjects (SHS; N = 21). All participants performed cardiopulmonary exercise
      testing. RESULTS: The HTR-ET achieved a significantly higher performance (255 +/-
      47 W, VO(2max) of 45.2 +/- 6.9 mL.kg(-1).min(-1)) in contrast to all other groups
      (HTR-D: 119 +/- 17 W, VO(2max) of 17.4 +/- 4.5 mL.kg(-1).min(-1); HTR-R: 119 +/-
      17 W, VO(2max) of 16.9 +/- 3.7 mL.kg(-1).min(-1); SHS: 184 +/- 19 W, VO(2max) of
      35.0 +/- 6.9 mL.kg(-1).min(-1)). The HR at maximal power output in the HTR-ET was
      169 +/- 17 bpm and similar to SHS (164 +/- 17 bpm), but significantly higher than
      HTR-D (125 +/- 16) and HTR-R (142 +/- 10). Maximal lactate concentration (LAmax)
      of HTR-ET was 9.9 +/- 2.2 mmol.L(-1), comparable to SHS (9.2 +/- 2.1 mmol.L(-1)),
      and significantly higher than HTR-D (5.5 +/- 1.5 mmol.L(-1)) and HTR-R (5.1 +/-
      1.0 mmol.L(-1)). CONCLUSIONS: Data suggest that HTR can perform high-volume and 
      intensity exercise training, reaching exercise performance comparable to or even
      exceeding values of sedentary or moderately trained healthy subjects.

PMID- 15570134
TI  - Exercise in heart failure: should aqua therapy and swimming be allowed?
AB  - PURPOSE: Although exercise training is established as an integrated part of
      treatment regimes in both patients with transmural myocardial infarction (MI) and
      chronic congestive heart failure (CHF), there is no consensus yet on the
      appropriateness of water exercises and swimming. One reason is the lack of
      information concerning both central hemodynamic volume and pressure responses
      during immersion in these patients. METHODS: This paper presents explorative
      studies on changes in cardiac dimensions and central hemodynamics during graded
      immersion and swimming in patients with moderate and/or severe MI and in patients
      with moderate and/or compensated severe CHF. For comparison purposes, healthy
      subjects were assessed. Measurements were performed by using Swan-Ganz right
      heart catheterization, subxiphoidal echocardiography, and Doppler
      echocardiography. RESULTS: The major findings were: 1) Indicators of an increase
      in preload were seen in patients with moderate and severe MI. In both patient
      groups, upright immersion to the neck and supine body position at rest in the
      water resulted in abnormal mean pulmonary artery pressure (PAm) and mean
      pulmonary capillary pressures (PCPm), respectively. During low-speed swimming (20
      25 m.min(-1)), the PAm and/or PCPm were higher than during supine cycle ergometry
      at a load of 100 W. 2) Left ventricular overload and decrease and/or no change in
      stroke volume occurred in patients with severe CHF who were immersed up to the
      neck. 3) Patient's well-being was maintained despite hemodynamic deterioration.
      CONCLUSION: The acute responses during immersion and swimming suggest the need
      for additional studies on long-term changes in cardiac dimensions and central
      hemodynamic in both patients with severe MI and severe CHF who undergo a swimming
      program, compared with nonswimming patients with MI and CHF of similar etiology
      and severity of disease.

PMID- 15570135
TI  - The role of regular physical activity in preeclampsia prevention.
AB  - Preeclampsia affects 2-7% of pregnancies and is a leading cause of maternal and
      fetal morbidity and mortality. Despite extensive study, the etiology of
      preeclampsia is poorly understood. Abnormal placental development, predisposing
      maternal constitutional factors, oxidative stress, immune maladaptation, and
      genetic susceptibility have all been hypothesized to contribute to the
      development of preeclampsia. Physical conditioning and preeclampsia have opposite
      effects on critical physiological functions. This suggests that regular prenatal
      exercise may prevent or oppose the progression of the disease. Epidemiologic
      studies show that occupational and leisure-time physical activity is associated
      with a reduced incidence of preeclampsia. We hypothesize that this protective
      effect results from one of more of the following mechanisms: 1) stimulation of
      placental growth and vascularity, 2) reduction of oxidative stress, and 3)
      exercise-induced reversal of maternal endothelial dysfunction. Future research
      should include prospective epidemiological case-control studies that accurately
      measure occupational and leisure-time physical activity. Controlled randomized
      clinical trials examining the effects of prenatal exercise on biochemical markers
      for endothelial dysfunction, placental dysfunction, and oxidative stress are also
      needed. If future research supports the idea that exercise effectively protects
      against preeclampsia, this would provide a low-cost intervention that could
      dramatically improve prenatal care for women at risk of this disease.

PMID- 15570136
TI  - Intermittent exercise test in chronic obstructive pulmonary disease patients: how
      do the pulmonary hemodynamics adapt?
AB  - PURPOSE: Endurance training is an important component of rehabilitation in
      patients with chronic obstructive pulmonary disease (COPD). In our study, we
      investigated the pulmonary hemodynamics' adaptation during a high-intensity
      intermittent exercise in such patients. METHODS: Eight patients underwent a 30
      min exercise, alternating a 4-min work set at their first ventilatory threshold
      with a 1-min exercise set at 90% of their maximal tolerated power output.
      Pulmonary arterial pressure was measured by means of a right heart catheter.
      Cardiac output was calculated using the Fick's principle applied to oxygen.
      RESULTS: VO(2), cardiac output, and ventilation increased during the first
      minutes of exercise and remained stable thereafter. Heart rate increased
      significantly and progressively to its maximal value from rest to the end of the
      test (P < 0.001). After an initial increase, stroke volume decreased
      significantly (P < 0.05). Pulmonary arterial pressure increased from rest (mean
      +/- SEM 23.9 +/- 2.1 mm Hg) to the fifth minute of exercise (41.6 +/- 2.8 mm Hg),
      and decreased significantly thereafter (35.2 +/- 3.3 mm Hg at the 30th minute) (P
      < 0.001). Total pulmonary vascular resistance decreased from rest to the end of
      the test (P < 0.001). CONCLUSION: The high-intensity 1-min bouts of work of our
      intermittent work exercise are well tolerated without pushing the pulmonary
      arterial pressure dramatically high in COPD patients.

PMID- 15570137
TI  - Delayed onset of transversus abdominus in long-standing groin pain.
AB  - Long-standing groin pain is a persistent problem that is commonly difficult to
      rehabilitate. Theoretical rationale indicates a relationship between the motor
      control of the pelvis and long-standing groin pain; however, this link has not
      been investigated. PURPOSE: The current experiment aimed to evaluate motor
      control of the abdominal muscles in a group of Australian football players with
      and without long-standing groin pain. METHODS: Ten participants with long
      standing groin pain and 12 asymptomatic controls were recruited for the study.
      Participants were elite or subelite Australian football players. Fine-wire and
      surface electromyography electrodes were used to record the activity of the
      selected abdominal and leg muscles during a visual choice reaction-time task
      (active straight leg raising). RESULTS: When the asymptomatic controls completed
      the active straight leg raise (ASLR) task, the transversus abdominus contracted
      in a feed-forward manner. However, when individuals with long-standing groin pain
      completed the ASLR task, the onset of transversus abdominus was delayed (P <
      0.05) compared with the control group. There were no differences between groups
      for the onset of activity of internal oblique, external oblique, and rectus
      abdominus (all P > 0.05). CONCLUSIONS: The finding that the onset of transversus
      abdominus is delayed in individuals with long-standing groin pain is important,
      as it demonstrates an association between long-standing groin pain and
      transversus abdominus activation.

PMID- 15570138
TI  - Tai Chi: improving functional balance and predicting subsequent falls in older
      persons.
AB  - PURPOSE: To determine whether improved functional balance through a Tai Chi
      intervention is related to subsequent reductions in falls among elderly persons.
      METHODS: Two hundred fifty-six healthy, physically inactive older adults aged 70
      92 (mean age +/- SD = 77.48 +/- 4.95), recruited from a local health system in
      Portland, OR, participated in a 6-month randomized controlled trial, with
      allocation to Tai Chi or exercise stretching control, followed by a 6-month
      postintervention follow-up. Functional balance measures included Berg balance
      scale, dynamic gait index, and functional reach, assessed during the 6-month
      intervention period (baseline, 3-month, and 6-month intervention endpoint) and
      again at the 6-month postintervention follow-up. Fall counts were recorded during
      the 6-month postintervention follow-up period. Data were analyzed through
      intention-to-treat analysis of variance and logistic regression procedures.
      RESULTS: Tai Chi participants who showed improvements in measures of functional
      balance at the intervention endpoint significantly reduced their risk of falls
      during the 6-month postintervention period, compared with those in the control
      condition (odds ratio (OR), 0.27, 95% confidence interval (CI), 0.07-0.96 for
      Berg balance scale; OR, 0.27, 95% CI, 0.09-0.87 for dynamic gait index; OR, 0.20,
      95% CI, 0.05-0.82 for functional reach). CONCLUSIONS: Improved functional balance
      through Tai Chi training is associated with subsequent reductions in fall
      frequency in older persons.

PMID- 15570139
TI  - Glycogen determination using periodic acid-schiff: artifact of muscle
      preparation.
AB  - PURPOSE: It is common practice for the staining of muscle glycogen with periodic
      acid-Schiff (PAS) to thaw and dry muscle sections before staining. The goal is to
      investigate whether this thawing step results in a systematic error that is
      independent of muscle fiber type and muscle physiological state. METHODS: Muscle
      samples from six fasted male subjects were obtained before or after 3 min of high
      intensity cycling. Each sample was sectioned; some sections were assessed for
      muscle fiber composition, and others were either thawed for 20 min or kept frozen
      before being PAS-stained for glycogen. The response to a 20-min freeze-thaw cycle
      was also assessed using rested and exercised rats as our experimental model, and
      the changes in glycogen were measured enzymatically. RESULTS: The inclusion of a
      20-min thawing step resulted in a significant reduction (P < 0.05) in the
      weighted average of the optical density of PAS (ODPAS) staining in both the
      nonexercised (15 +/- 1.4%) and exercised human muscles (15 +/- 1.3%), with the
      absolute extent being greater in the nonexercised muscle samples (P < 0.05).
      Moreover, the observed decrease in ODPAS was greatest in Type IIa fibers for both
      the nonexercised (P < 0.05) and exercised (P < 0.05) muscle samples. The findings
      in rats suggest that the muscle damage associated with freeze-thawing is
      responsible for this stimulation of glycogenolysis. CONCLUSION: For the
      quantitative histochemical measurement of glycogen content in skeletal muscle,
      the common practice of thawing unfixed muscle sections before PAS staining should
      be abandoned because this causes glycogen breakdown, the extent of which varies
      across muscle fiber types and prior exercise history.

PMID- 15570140
TI  - Exercise restores immune cell function in energy-restricted rats.
AB  - OBJECTIVE: To evaluate the effect of chronic moderate-intensity exercise upon the
      alterations of immune system cell function induced by energy restriction.
      METHODS: Forty male Wistar rats were randomly assigned to the following groups:
      sedentary animals fed ad libitum (SF, N = 10) or submitted to energy restriction
      (SER, N = 10, receiving 50% of the mean amount of chow consumed by SF); and
      trained animals fed ad libitum (TF, N = 10) or submitted to energy restriction
      (TER, N = 10), who exercised on a treadmill (at 60-65%VO(2max) 5 d.wk(-1) for 10
      wk(-1), after 30 d under the restriction protocol. The incorporation of [2-(14)C]
      thymidine by lymphocytes obtained from the spleen and mesenteric lymph nodes,
      plasma glucose and glutamine concentration, and cytokine production by cells
      cultivated in the presence of glutamine were measured in all groups, 24 h after
      the last exercise session. Two-way ANOVA and Tukey's posttest were employed for
      the statistical analysis. RESULTS: Training induced an increase in the
      proliferative response and in the production of gamma-interferon and interleukin
      1 (P < 0.05) in cells from the spleen and lymph nodes of SER, in which these
      parameters were diminished when compared with SF (P < 0.05). SER spleen and lymph
      node cells produced more TNF (26 and 42%, respectively) and IL-2 (49 and 42%,
      respectively) than SF. The Th1-like diversion of the immune response observed in
      SER persisted after training. Partial recovery of the decreased SER plasma
      glutamine concentration and muscle glutamine synthase mRNA was observed.
      CONCLUSIONS: Training induced the recovery of the proliferative capacity of
      lymphocytes from SER, probably due to the partial restoration of plasma glutamine
      levels, but did not interfere with the diversion towards a Th1-type immune
      response induced by food restriction.

PMID- 15570141
TI  - Oxidative stress responses in older men during endurance training and detraining.
AB  - PURPOSE: Aging is associated with increased oxidative stress, whereas systematic
      exercise training has been shown to improve quality of life and functional
      performance of the aged. This study aimed to evaluate responses of selected
      markers of oxidative stress and antioxidant status in inactive older men during
      endurance training and detraining. METHODS: Nineteen older men (65-78 yr) were
      randomly assigned into either a control (C, N = 8) or an endurance-training (ET,
      N = 11, three training sessions per week, 16 wk, walking/jogging at 50-80% of
      HR(max)) group. Before, immediately posttraining, and after 4 months of
      detraining, subjects performed a progressive diagnostic treadmill test to
      exhaustion (GXT). Plasma samples, collected before and immediately post-GXT, were
      analyzed for malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels, total
      antioxidant capacity (TAC), and glutathione peroxidase activity (GPX). RESULTS:
      ET caused a 40% increase in running time and a 20% increase in maximal oxygen
      consumption (VO(2max)) (P < 0.05). ET lowered MDA (9% at rest, P < 0.01; and 16%
      postexercise, P < 0.05) and 3-NT levels (20% postexercise, P < 0.05), whereas it
      increased TAC (6% at rest, P < 0.01; and 14% postexercise, P < 0.05) and GPX (12%
      postexercise, P < 0.05). However, detraining abolished these adaptations.
      CONCLUSIONS: ET may attenuate basal and exercise-induced lipid peroxidation and
      increase protection against oxidative stress by increasing TAC and GPX activity.
      However, training cessation may reverse these training-induced adaptations.

PMID- 15570142
TI  - Ingestion of casein and whey proteins result in muscle anabolism after resistance
      exercise.
AB  - PURPOSE: Determination of the anabolic response to exercise and nutrition is
      important for individuals who may benefit from increased muscle mass. Intake of
      free amino acids after resistance exercise stimulates net muscle protein
      synthesis. The response of muscle protein balance to intact protein ingestion
      after exercise has not been studied. This study was designed to examine the acute
      response of muscle protein balance to ingestion of two different intact proteins
      after resistance exercise. METHODS: Healthy volunteers were randomly assigned to
      one of three groups. Each group consumed one of three drinks: placebo (PL; N =
      7), 20 g of casein (CS; N = 7), or whey proteins (WH; N = 9). Volunteers consumed
      the drink 1 h after the conclusion of a leg extension exercise bout. Leucine and
      phenylalanine concentrations were measured in femoral arteriovenous samples to
      determine balance across the leg. RESULTS: Arterial amino acid concentrations
      were elevated by protein ingestion, but the pattern of appearance was different
      for CS and WH. Net amino acid balance switched from negative to positive after
      ingestion of both proteins. Peak leucine net balance over time was greater for WH
      (347 +/- 50 nmol.min(-1).100 mL(-1) leg) than CS (133 +/- 45 nmol.min(-1).100 mL(
      1) leg), but peak phenylalanine balance was similar for CS and WH. Ingestion of
      both CS and WH stimulated a significantly larger net phenylalanine uptake after
      resistance exercise, compared with the PL (PL -5 +/- 15 mg, CS 84 +/- 10 mg, WH
      62 +/- 18 mg). Amino acid uptake relative to amount ingested was similar for both
      CS and WH (approximately 10-15%). CONCLUSIONS: Acute ingestion of both WH and CS
      after exercise resulted in similar increases in muscle protein net balance,
      resulting in net muscle protein synthesis despite different patterns of blood
      amino acid responses.

PMID- 15570143
TI  - Validity of a questionnaire to assess historical physical activity in older
      women.
AB  - PURPOSE: To compare historical physical activity recall to original physical
      activity questionnaires collected at four time points over a 17-yr period in
      postmenopausal women. METHODS: This study examined the recall of physical
      activity (PA) data collected as part of a clinical trial of a walking
      intervention and subsequent follow-up in 163 white postmenopausal women (74 +/- 4
      yr). Physical activity levels were measured with a modified version of the
      Paffenbarger Physical Activity Questionnaire (1982, 1985, 1995, 1999) throughout
      the duration of the study. The interviewer-administered historical physical
      activity questionnaire (HPAQ) asked participants to recall in the year 2000 what
      PA they performed in 1982, 1985, 1995, and over the past year. Spearman
      correlation coefficients were used to compare subjects' historical recall of
      activity for each time period with the actual questionnaire data collected during
      that time period. RESULTS: Statistically significant correlations were found
      between the historical PA recall and the original PA questionnaires at each of
      the time points measured (rho = 0.39-0.62, P < 0.0001). The magnitude of the
      correlations increased as the time length of recall decreased. CONCLUSION: It
      appears that historical recall of leisure physical activity can be reasonably
      estimated by questionnaire over a substantial time period in older women.

PMID- 15570144
TI  - Effects of cardiorespiratory fitness on healthcare utilization.
AB  - BACKGROUND: Prospective study examining the relationship between
      cardiorespiratory fitness level and incidence of medical treatments during a 1-yr
      period before each of two examinations. A subset was also evaluated to assess
      whether improvement in fitness affected incidence of treatments. METHODS AND
      RESULTS: Part I: Six thousand six hundred seventy-nine healthy male subjects
      underwent medical examinations on two occasions, including a maximal exercise
      test. Division of subjects by fitness into quartiles (Q1 = low fitness through Q4
      = high fitness) revealed an inverse relationship between fitness and outcome
      measures. Men in the low-fitness group had more office visits and overnight
      hospital stays than men in the high-fitness group (3.5% (Q1) vs 1.6% (Q4) men had
      10+ office visits, and 10% (Q1) vs 5.0% (Q4) men had overnight hospital stays, P
      < 0.0001). These differences held after adjustment for potential confounding
      variables (age, follow-up yr, blood pressure, cholesterol, and smoking). Part II:
      Subjects in this subset (N = 2974) were evaluated to compare overnight hospital
      stays between low-fit men who remained low fit at the second examination, and low
      fit men who became fit by the second examination. This cohort was divided into
      fitness tertiles (T1 = low fitness through T3 = high fitness). Those who improved
      their fitness by the time of the second examination had a decreased number of
      overnight hospital stays, compared with those who remained unfit at the time of
      the second examination (10.2% (T1 at second visit) vs 5.9% (T3 at second visit)
      had overnight hospital stays, P < 0.03). CONCLUSIONS: Men who maintain or become
      fit are less likely to have physician visits or overnight hospital stays,
      compared with men who are unfit.

PMID- 15570145
TI  - Nonoccupational physical activity by degree of urbanization and U.S. geographic
      region.
AB  - PURPOSE: To estimate levels of nonoccupational leisure-time physical activity
      (LTPA) by degree of urbanization and geographic region of the United States.
      METHODS: Participants were respondents to the Behavioral Risk Factor Surveillance
      System (BRFSS) in 2001 (N = 137,359). Moderate- and vigorous-intensity LTPA was
      categorized as meeting recommended levels, insufficient, or inactive. The U.S.
      Department of Agriculture rural-urban continuum codes were used to describe
      degrees of urbanization (metro, large urban, small urban, and rural). Geographic
      regions were defined by the U.S. Bureau of the Census (Northeast, Midwest, South,
      and West). Prevalence estimates were calculated using sample weights to account
      for the design of the BRFSS. Multivariate logistic regression analyses examined
      regional differences in the odds of physical inactivity (physically inactive vs
      insufficient or meets) by degree of urbanization after adjustment for sex, age,
      race, BMI, education, and occupational physical activity. RESULTS: Large urban
      areas (49.0%) and the western United States (49.0%) had the highest prevalence of
      recommended levels of LTPA. Rural areas (24.1%) and the southern United States
      (17.4%) had the highest prevalence of inactivity. Adults living in the four
      urbanization categories of the midwestern (metro (OR = 1.47, 95% CI = 1.31,
      1.65), large urban (OR = 1.83, 95% CI = 1.51, 2.23), small urban (OR = 1.99, 95%
      CI = 1.65, 2.40), and rural (OR = 2.59, 95% CI = 1.35, 4.97)); and southern
      (metro (OR = 1.70, 95% CI = 1.53, 1.88), large urban (OR = 2.04, 95% CI = 1.72,
      2.41), small urban (OR = 2.32, 95% CI = 2.02, 2.67), and rural (OR = 5.49, 95% CI
      = 2.82, 10.68)) U.S. regions were more likely to be inactive than adults living
      in similar areas of the western United States. Adults in northeast metro and
      large urban areas (OR = 1.62, 95% CI = 1.45, 1.81; and OR = 1.37, 95% CI = 1.08,
      1.74, respectively) were more likely to be inactive than those residing in
      western metro and large urban areas. CONCLUSION: The prevalence of physical
      inactivity varies by degree of urbanization and geographic region of the United
      States.

PMID- 15570146
TI  - Authentic evaluation of forehand groundstrokes in young low- to intermediate
      level tennis players.
AB  - PURPOSE: In the present study the ForeGround test, a new procedure to assess
      forehand groundstroke performance in rally patterns authentic to low- and
      intermediate-level tennis play, was evaluated as to its value for research
      purposes. METHODS: The ForeGround protocol was enacted on a midi tennis court. It
      consists of 18 programmed rallies, reproducing neutral and offensive situations
      as they occur during midi tennis game play, driven by a test leader. Quality of
      the forehand groundstrokes was determined from simultaneous measurements of
      success rate, precision of lateral and longitudinal ball placement, and ball
      velocity. A velocity-precision (VP) and velocity-precision-success (VPS) index
      were calculated to reveal interactive effects. The validity and sensitivity of
      the ForeGround procedure in the target population were determined by verifying
      whether test scores reflected minor differences in tennis experience. RESULTS:
      More experienced players scored significantly higher than beginning players for
      success rate, ball velocity, precision of ball placement, VP, and VPS. High to
      moderate intraclass correlation coefficients in this open skill test indicated
      satisfactory test reliability. CONCLUSION: It was concluded that the ForeGround
      procedure is a concise, authentic, sensitive, accurate, reliable, and valid
      instrument for the assessment of forehand groundstroke quality in low- to
      intermediate-level tennis players.

PMID- 15570147
TI  - The effect of carbohydrate mouth rinse on 1-h cycle time trial performance.
AB  - PURPOSE AND METHOD: To investigate the possible role of carbohydrate (CHO)
      receptors in the mouth in influencing exercise performance, seven male and two
      female endurance cyclists (VO(2max) 63.2 +/- 2.7 (mean +/- SE) mL.kg*(-1).min(
      1)) completed two performance trials in which they had to accomplish a set amount
      of work as quickly as possible (914 +/- 40 kJ). On one occasion a 6.4%
      maltodextrin solution (CHO) was rinsed around the mouth for every 12.5% of the
      trial completed. On the other occasion, water (PLA) was rinsed. Subjects were not
      allowed to swallow either the CHO solution or water, and each mouthful was spat
      out after a 5-s rinse. RESULTS: Performance time was significantly improved with
      CHO compared with PLA (59.57 +/- 1.50 min vs 61.37 +/- 1.56 min, respectively, P
      = 0.011). This improvement resulted in a significantly higher average power
      output during the CHO compared with the PLA trial (259 +/- 16 W and 252 +/- 16 W,
      respectively, P = 0.003). There were no differences in heart rate or rating of
      perceived exertion (RPE) between the two trials (P > 0.05). CONCLUSION: The
      results demonstrate that carbohydrate mouth rinse has a positive effect on 1-h
      time trial performance. The mechanism responsible for the improvement in high
      intensity exercise performance with exogenous carbohydrate appears to involve an
      increase in central drive or motivation rather than having any metabolic cause.
      The nature and role of putative CHO receptors in the mouth warrants further
      investigation.

PMID- 15570148
TI  - Individual Interdependence between nocturnal ANS activity and performance in
      swimmers.
AB  - PURPOSE: Variations in autonomic nervous system activity (ANS) and variations in
      performances have been shown to be correlated at the group level in swimmers. The
      aim of the study was to investigate the strength of that relationship at the
      individual level. METHODS: Seven regional-level swimmers (four male, age 16.6 +/-
      05 yr, 6.4 +/- 0.9 yr of practice) were included in the study. They performed
      maximal aerobic performance on a 400-m freestyle race before and after a 3-wk
      intensive training period, and following a 2-wk tapering period. ANS activity was
      assessed through heart rate variability (HRV) indices measured the night before
      each race and twice a week along the protocol. RESULTS: All HRV indices were
      altered, with global and parasympathetic indices decreasing from W1 to W3 in the
      whole group, while they increased until W5 in five swimmers, and continuously
      decreased in two. Best performances were respectively realized when global and
      parasympathetic indices of HRV were highest. Importantly, the relationship
      between the changes in performances and the changes in HRV indices was strong
      (DeltaPerf = -1.232 to 1.625.DeltaHF(wavelet), R(2) = 0.5); the greater the
      rebound in ANS activity after W3, the greater the performance improvement, and
      reciprocally. CONCLUSION: Performance is correlated with nocturnal ANS activity
      at an individual level. The decrease in ANS activity during intensive training is
      correlated with the loss in performance, and the rebound in ANS activity during
      tapering tracks with the gain in performance. Interestingly, the speed of the
      rebound during the tapering period was quite different between swimmers. ANS
      activity measurement may be useful to design and control individual training
      periods and to optimize the duration of tapering.

PMID- 15570149
TI  - Effects of resistance, endurance, and concurrent exercise on training outcomes in
      men.
AB  - The specificity of training principle predicts that combining resistance and
      endurance training (concurrent training) could interfere with the maximum
      development of strength and endurance capacity that results from either type of
      training alone. PURPOSE: To determine whether endurance and resistance training
      performed concurrently produces different performance and physiologic responses
      compared with each type of training alone. METHODS: Untrained male volunteers
      were randomly assigned to one of three groups: endurance training (ET, N = 12);
      resistance training (RT, N = 13); and concurrent training (CT, N = 16). The
      following measurements were made on all subjects before and after 12 wk of
      training: weight, percent body fat, peak oxygen consumption (VO(2peak)),
      isokinetic peak torque and average power produced during single-leg flexion and
      extension at 60 and 180 degrees.s, one-repetition maximum (1RM) leg press, 1RM
      bench press, vertical jump height, and calculated jump power. RESULTS: Weight and
      lean body mass (LBM) increased significantly in the RT and CT groups (P < 0.05).
      Percent body fat was significantly decreased in the ET and CT groups. VO(2peak)
      was significantly improved only in the ET group. Peak torque during flexion and
      extension at 180 degrees.s(-1) increased in the RT group. Improvements in 1RM leg
      press and bench press were significant in all groups, but were significantly
      greater in the RT and CT compared to the ET group. Jump power improved
      significantly only in the RT group, and no group showed a significant change in
      vertical jump height. CONCLUSIONS: Concurrent training performed by young,
      healthy men does not interfere with strength development, but may hinder
      development of maximal aerobic capacity.

PMID- 15570150
TI  - Energy expenditure of walking and running: comparison with prediction equations.
AB  - PURPOSE: This study established the published prediction equations for the energy
      expenditure of walking and running compared with the measured values. To make
      this comparison we first determined whether differences exist in energy
      expenditure for 1600 m of walking versus running, and whether energy expenditure
      differences occur due to being on the track or treadmill. METHODS: Energy was
      measured via indirect calorimetry in 24 subjects while walking (1.41 m.s(-1)) and
      running (2.82 m.s(-1)) 1600 m on the treadmill. A subgroup also performed the
      1600-m run/walk on the track. The measured energy expenditures were compared with
      published prediction equations. RESULTS: Running required more energy (P < 0.01)
      for 1600 m than walking (treadmill: running 481 +/- 20.0 kJ, walking 340 +/- 14
      kJ; track: running 480 +/- 23 kJ, walking 334 +/- 14 kJ) on both the track and
      treadmill. Predictions using the ACSM or Leger equations for running, and the
      Pandolf equation for walking, were similar to the actual energy expenditures for
      running and walking (total error: ACSM: -20 and 14.4 kJ, respectively; Legers
      walking: -10.1 kJ; Pandolf walking: -10.0 kJ). An overestimation (P < 0.01) for
      1600 m was found with the McArdle's table for walking and running energy
      expenditure and with van der Walt's prediction for walking energy expenditure,
      whereas the Epstein equation underestimated running energy expenditure (P <
      0.01). CONCLUSION: Running has a greater energy cost than walking on both the
      track and treadmill. For running, the Leger equation and ACSM prediction model
      appear to be the most suitable for the prediction of running energy expenditure.
      The ACSM and Pandolf prediction equation also closely predict walking energy
      expenditure, whereas the McArdle's table or the equations by Epstein and van der
      Walt were not as strong predictors of energy expenditure.

PMID- 15570151
TI  - Comparison of two approaches to structured physical activity surveys for
      adolescents.
AB  - PURPOSE: To compare the test-retest reliability, convergent validity, and overall
      feasibility/ usability of activity-based (AB) and time-based (TB) approaches for
      obtaining self-reported moderate-to-vigorous physical activity (MVPA) from
      adolescents. METHODS: Adolescents (206 females and 114 males) completed two 3-d
      physical activity recalls using the AB and TB surveys, which contained identical
      lists of physical activities. The participants wore an MTI Actigraph
      accelerometer for the same period. RESULTS: The TB instrument took about 3 min
      longer to complete (P = 0.022). Overall 2-d test-retest correlations for MVPA
      were similar for the two surveys (r = 0.676 and 0.667), but the girls had higher
      reliability on the AB survey than the boys (girls: r = 0.713; boys: r = 0.568).
      The overall 3-d correlations for MVPA surveys and Actigraph counts varied by
      gender (girls: AB = 0.265 vs TB = 0.314; boys: AB = 0.340 vs TB = 0.277).
      Correlations for vigorous physical activity and Actigraph counts were higher for
      the AB than for the TB (r = 0.281 vs 0.162). As the interval between completing
      the surveys and the days being recalled increased, reliability and validity were
      lower, especially for the AB survey. CONCLUSION: For both genders, either
      approach is acceptable for obtaining MVPA information on a single day, but the TB
      approach appears to be slightly favored over the AB approach for obtaining
      multiple days of MVPA. A 3-d recall period appears to be too long for accurate
      recall of MVPA information from either instrument. For both genders, the surveys
      overestimated activity levels; thus, self-reports should be supplemented with
      objective data.

PMID- 15570152
TI  - Limitations of ordinary least squares models in analyzing repeated measures data.
AB  - PURPOSE: To a) introduce and present the advantages of linear mixed models using
      generalized least squares (GLS) when analyzing repeated measures data; and b)
      show how model misspecification and an inappropriate analysis using repeated
      measures ANOVA with ordinary least squares (OLS) methodology can negatively
      impact the probability of occurrence of Type I error. METHODS: The effects of
      three strength-training groups were simulated. Strength gains had two slope
      conditions: null (no gain), and moderate (moderate gain). Ten subjects were
      hypothetically measured at five time points, and the correlation between
      measurements within a subject was modeled as compound symmetric (CS),
      autoregressive lag 1 (AR(1)), and random coefficients (RC). A thousand data sets
      were generated for each correlation structure. Then, each was analyzed four times
      -once using OLS, and three times using GLS, assuming the following
      variance/covariance structures: CS, AR(1), and RC. RESULTS: OLS produced
      substantially inflated probabilities of Type I errors when the
      variance/covariance structure of the data set was not CS. The RC model was less
      affected by the actual variance/covariance structure of the data set, and gave
      good estimates across all conditions. CONCLUSIONS: Using OLS to analyze repeated
      measures data is inappropriate when the covariance structure is not known to be
      CS. Random coefficients growth curve models may be useful when the
      variance/covariance structure of the data set is unknown.

PMID- 15570153
TI  - RNA-binding proteins and neural development: a matter of targets and complexes.
AB  - RNA-binding proteins control multiple steps of nuclear and cytoplasmic RNA
      processing including alternative splicing, stabilization, transport and
      translational repression of RNAs. Here we present existing evidence showing that
      RNA-binding proteins expressed in the nervous system are required in many steps
      of its development and play multiple roles during the life of a neuron. We
      describe emerging views based on recent studies strongly suggesting that RNA
      binding proteins cooperate actively within neurons in large multifunctional
      complexes to regulate the flow of information encoded in ribonomes in a
      coordinated fashion.

PMID- 15570154
TI  - Reduction of serotonin transporters of patients with chronic fatigue syndrome.
AB  - To assess the involvement of serotonin in the symptoms of chronic fatigue
      syndrome, we investigated the serotonergic neurotransmitter system of chronic
      fatigue syndrome patients by the positron emission tomography (PET). Here we show
      that the density of serotonin transporters (5-HTTs) in the brain, as determined
      by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral
      subdivision of the anterior cingulate as compared with that in normal volunteers.
      This subdivision is different from that in the dorsal anterior cingulate in which
      binding potential values of individual patient showed a weak negative correlation
      with self-reported pain score of the patients. Therefore, an alteration of
      serotonergic system in the rostral anterior cingulate plays a key role in
      pathophysiology of chronic fatigue syndrome.

PMID- 15570155
TI  - BOLD fMRI signal increases with age in selected brain regions in children.
AB  - To determine whether the BOLD signal used in fMRI is age dependent in childhood,
      332 healthy children (age 4.9-18.9 years) performed tasks in a periodic block
      design during 3 T fMRI: (1) a verb generation task interleaved with a finger
      tapping task; (2) a word-picture matching task interleaved with an image
      discrimination task. Significant correlations between percent signal change in
      BOLD effect and age occurred in left Broca's, middle frontal, Wernicke's, and
      inferior parietal regions, and anterior cingulate during the verb generation
      task; in precentral, postcentral, middle frontal, supplementary motor, and
      precuneus regions during the finger tapping task; and in bilateral lingula gyri
      during the word-picture matching task. Thus, BOLD effect increases with age in
      children during sensorimotor and language tasks.

PMID- 15570156
TI  - Neural progenitor cells promote corticospinal axon growth in organotypic co
      cultures.
AB  - The CNS is limited in regeneration following injury in adult mammals. Recent
      studies show that the transplantation of the neuronal progenitor cells is useful
      in promoting regeneration. However, the mechanisms of action of the transplanted
      neural progenitor cells have not been clarified. In this study, we used
      organotypic co-cultures with neonatal brain cortex and spinal cord as an in vitro
      assay system for assessing the factors that regulate corticospinal axonal growth.
      Our results show that the transplantation of neural progenitor cells enhanced
      corticospinal axon growth in these co-cultures. In addition, neural progenitor
      cell conditioned medium also significantly promoted axonal growth. These findings
      strongly suggest that factors derived from neural progenitor cells participate in
      the effect on axonal growth.

PMID- 15570157
TI  - Brain activation to emotional words in depressed vs healthy subjects.
AB  - Depression involves either enhanced processing of negative stimuli or diminished
      processing of positive stimuli. We used functional magnetic resonance imaging to
      assess brain activation in depressed vs healthy participants. Fifteen
      participants diagnosed with major depressive disorder and 15 controls were
      scanned during a lexical decision task involving neutral, happy, sad, and threat
      related words. For happy words, depressed subjects exhibited less activation than
      did controls to happy words in fronto-temporal and limbic regions. For sad words,
      depressed subjects showed more activation than did controls in the inferior
      parietal lobule and less activation in the superior temporal gyrus and
      cerebellum, suggesting a complex activation pattern that varies for neural sub
      circuits that may be associated with different cognitive or behavioral processes.

PMID- 15570158
TI  - Is the N400 category-specific? A face and language processing study.
AB  - N400 event-related potential (ERP) components have been observed during semantic
      incongruity detection in language, face identity and/or expression. However, it
      is still unclear whether semantic processing is functionally equivalent, since no
      study has directly investigated within the same participants the occurrence of
      the N400s for language and faces. We recorded ERPs while subjects performed
      incongruity detection on words, facial identities and facial expressions, with
      conditions matched to involve context integration. N400s were identified on
      central-parietal electrodes only for language and face identity processing. Scalp
      topographies of these N400s differed but a LORETA inverse solution identified a
      common functional generator in the left lateral frontal cortex, suggesting a
      general role of this brain region in selecting and contextually integrating
      semantic information.

PMID- 15570159
TI  - CNR/Pcdhalpha family in subplate neurons, and developing cortical connectivity.
AB  - The cadherin-related neuronal receptor (CNR)/protocadherin (Pcdh) alpha family is
      one of the diverse protocadherin families identified as a candidate diversified
      membrane-associated component regulating the formation of neuronal connectivity.
      However, its expression during neural circuit formation has not been examined in
      detail. Here, we used a conserved sequence to study the expression of this
      protein family during the development of neocortical connectivity, by
      immunohistochemistry and in situ hybridization. The proteins were detected in
      developing thalamocortical and corticofugal axons, and in subplate neurons, which
      pioneer these axon tracts. The expression in subplate neurons was confirmed by
      birth-date labeling with BrdU, and by examination in homozygous reeler mice. This
      pattern of CNR/Pcdhalpha expression suggests its involvement in the development
      of neocortical connectivity.

PMID- 15570160
TI  - Colonic inflammation increases Na+ currents in bladder sensory neurons.
AB  - The purpose of this study was to determine whether sensitization of pre-spinal
      afferents induced by colonic inflammation can affect the physiology of the
      urinary bladder. Tetrodotoxin-resistant (TTX-R) Na+ currents were examined in
      bladder sensory neurons after experimental colitis. Cell bodies of bladder dorsal
      root ganglia were retrogradely labeled and TTX-R Na+ currents were recorded in
      capsaicin-sensitive neurons. Colitis significantly enhanced response of bladder
      neurons to capsaicin by approximately 60% and the peak amplitude of TTX-R Na+
      current by 51%. These results suggest that colonic inflammation leads to
      increased excitability of nociceptive bladder neurons.

PMID- 15570161
TI  - Spatiotemporal analyses of the N170 for human faces, animal faces and objects in
      natural scenes.
AB  - We assessed the specificity to human faces of the N170 ERP component in the
      context of natural scenes. Subjects categorized photographs containing human
      faces, animal faces and various objects. Spatiotemporal topography analyses were
      performed on the individual ERP data. ERPs elicited by animal faces were similar
      to human faces ERPs but with a delayed face activity. In the N170 time window,
      ERPs to human and animal faces had a different topography compared with object
      ERPs. Such data suggest that N170 generators might process various stimuli with a
      coarse facial organization and show the care that must be taken in comparing
      scalp signal to faces and other objects as they are probably generated, at least
      partially, by different cortical sources.

PMID- 15570162
TI  - Correlated brain stem and cortical evoked responses to auditory tone change.
AB  - Numerous human studies have separately observed the effects of auditory stimuli
      at brain stem and cortical levels, but little research has focused on possible
      functional coupling between these diverse brain areas. The present study recorded
      the cortical C-process [5] evoked by a pitch change between two successive tones,
      as well as the brain stem frequency-following response (FFR) evoked by each tone.
      The results replicated expected C-process component waveforms, including a late,
      negative (N2) component. FFR spectral intensity differences between the two tones
      were significantly correlated with N2 amplitude. These results suggest that
      signal processing reflected in long-latency auditory evoked response components
      is not exclusively a cortical phenomenon, but also depends upon patterns of
      neural processing occurring in brain stem pathways.

PMID- 15570163
TI  - Enhanced smooth pursuit eye movements in patients with bilateral vestibular
      deficits.
AB  - Patients with bilateral vestibular deficits experience unsteady gait and
      oscillopsia that can reduce the quality of life, though many patients adapt
      remarkably well and lead mostly normal lives. One source of adaptation could be
      the ability of sensory-motor systems to compensate for the vestibular loss by
      adaptive enhancement of their performance. We studied smooth-pursuit eye
      movements in five patients and six healthy control subjects using a step-ramp
      paradigm. Eye movements were measured with scleral search coils. Patients showed
      open- and closed-loop pursuit gains that were about 9% higher than controls. We
      suggest that the challenge of living with a deficient vestibular system caused an
      enhancement in the pursuit system, which contributes to the patient's overall
      compensation.

PMID- 15570164
TI  - Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey.
AB  - We have studied the effects of stimulating the pedunculopontine nuclei through a
      fully implanted macroelectrode with a s.c. implantable pulse generator whose
      parameters can be programmed telemetrically, in a macaque before and after
      inducing Parkinsonian akinesia with MPTP. Our results show that in the normal
      monkey high frequency stimulation of the pedunculopontine nuclei reduces motor
      activity while low frequency stimulation increases it significantly over
      baseline. After making the monkey Parkinsonian with MPTP, unilateral low
      frequency stimulation of the pedunculopontine nuclei led to significant increases
      in activity. These results suggest that pedunculopontine nuclei stimulation could
      be clinically effective in treating advanced Parkinson's disease and other
      akinetic disorders.

PMID- 15570165
TI  - A motor resonance mechanism in children? Evidence from subdural electrodes in a
      36-month-old child.
AB  - The presence of a neural mechanism matching execution and observation of actions
      in the adult human brain is well established. In children, however, description
      of a resonance motor mechanism is still preliminary. In the present study, we
      recorded electroencephalographic signals from a subdural 64-contact grid
      electrode in a 36-month-old child with epilepsy. Spectral analysis was performed
      on sequences where the child drew with her right hand, watched an experimenter
      drawing with his right hand or was at rest. Contact sites corresponding to
      sensorimotor areas were discovered where absolute power was decreased during both
      observation and execution of hand/arm actions. These data suggest the presence of
      a mirror neuron system early in the developing brain.

PMID- 15570166
TI  - Dyslexics' eye fixations may accommodate to hemispheric desynchronization.
AB  - We argue that the vertical division of the fovea and the hemispheric division of
      the brain condition reading, and that hemispheric desynchronization is a proximal
      cause of dyslexia. We predict that dyslexics' fixation behaviour in reading
      accommodates to problematic hemispheric transfer/coordination, with fixations
      projecting more letter-information directly to the left hemisphere to facilitate
      processing. We analysed eye movements of 24 dyslexics and 24 normal readers.
      Dyslexics fixated closer to word beginning than did normal readers, projecting
      more of the word directly to the left hemisphere. Both groups produced comparable
      fixation durations at the beginning of the word; further into the word the
      dyslexics produced longer fixation durations. The results support a model of
      dyslexia based on hemispheric desynchronization.

PMID- 15570167
TI  - Pre-attentive detection of motion direction changes in normal aging.
AB  - Effects of normal aging on pre-attentive detection of changes in motion direction
      were evaluated. Young, middle-aged, and older subjects performed a visual central
      task while standard and deviant gratings varying in motion direction were
      presented outside the focus of attention. A greater negativity in the event
      related potentials (ERPs) to deviants was observed in all groups at posterior
      sites within the N2 latency range. Visual mismatch negativity (vMMN) reached its
      peak between 145 and 165 ms irrespective of age. However, significant age-related
      changes observed in vMMN mean amplitude may suggest that the pre-attentive visual
      detection become less efficient in older subjects. This could lead to age-related
      deficits in switching attention to potentially salient visual changes.

PMID- 15570168
TI  - Prefrontal cortex serotonin, stress, and morphine-induced nucleus accumbens
      dopamine.
AB  - Uncontrollable, but not controllable, stress produces a persistent potentiation
      of morphine-induced nucleus accumbens dopamine (DA) efflux and morphine-induced
      medial prefrontal cortex serotonin (5-HT) efflux. Here we investigate medial
      prefrontal cortex 5-HT mediation of this potentiation. Male Sprague-Dawley rats
      received bilateral medial prefrontal cortex microinjections of the neurotoxin 5,7
      dihydroxytriptamine (5,7-DHT, 8 microg/microl/side), which selectively depleted
      medial prefrontal cortex 5-HT, or vehicle (Sham), and cannula implantation in the
      nucleus accumbens shell. After 2 weeks, rats received either uncontrollable
      stress or no stress. Microdialysis and morphine (3 mg/kg) treatment were
      performed the following day. Morphine produced an enhanced increase in DA in the
      Stress-Sham group that was completely blocked by 5,7-DHT lesions, suggesting that
      5-HT in the medial prefrontal cortex mediates this potentiation.

PMID- 15570169
TI  - Angiotensin receptor gene expression in candesartan mediated neuroprotection.
AB  - Male Wistar rats were treated with an angiotensin AT1 receptor antagonist,
      candesartan cilexetil (TCV-116, 1 mg/kg/day) over a 4-week period. Systolic blood
      pressure was significantly reduced by 14% after 1 week and remained stable for
      the next 3 weeks compared with controls. Up-regulation of AT2, but not AT1,
      receptor gene expression by 3.4-fold and 5.0-fold was observed 1 and 4 weeks
      after treatment. Middle cerebral artery occlusion caused significantly reduced
      infarct volumes in TCV-116-treated rats, by about 30% when compared with control
      rats. Neurological scores were also improved in treated rats. These results
      suggest that the neuroprotective effects of TCV-116 may be mediated through AT1
      receptor antagonism and AT2 receptor up-regulation.

PMID- 15570170
TI  - Restoration of axotomy-induced PACAP gene induction in SCID mice with CD4+ T
      lymphocytes.
AB  - PACAP is a neuropeptide with putative neuroprotective, regenerative, and
      immunomodulatory actions. PACAP mRNA is up-regulated in motor neurons following
      facial nerve axotomy in wild type, but not immunodeficient SCID mice. Because
      CD4+ lymphocytes appear to be neuroprotective in facial nerve and other injury
      models, we studied PACAP gene expression in SCID mice preinfused with CD4+
      enriched splenocytes. Whereas the mean number of PACAP hybridizing neurons after
      axotomy was reduced by 75% in uninfused SCID mice, infusion of CD4+ enriched
      splenocytes restored the number to a value not significantly different than
      controls. The CD4+ cell-dependent induction of PACAP in motor neurons may thus be
      a factor in the cascade of events triggered by immune cells that ultimately lead
      to nerve regeneration.

PMID- 15570171
TI  - Activation of Ras in neurons modifies synaptic vesicle docking and release.
AB  - We have recently demonstrated that constitutive activation of Ha-Ras in
      differentiated neurons induces structural remodeling of both axons and dendrites
      in a transgenic mouse model (referred as synRas mice). Here we show that this
      activation of neuronal Ras enhances docking of synaptic vesicles to active zones,
      thereby leading to an increase in the size of the readily releasable pool of
      vesicles, while the size of the total pool of synaptic vesicles remained
      unchanged. The morphological phenotype was associated with corresponding
      increases in the probability of glutamate release as revealed by changes in short
      term synaptic plasticity. We, therefore, conclude that neuronal Ras activity
      contributes to the regulation of synaptic plasticity in adult mammalian brain at
      the presynaptic level.

PMID- 15570172
TI  - ApoE isoform affects LTP in human targeted replacement mice.
AB  - Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk
      of Alzheimer disease and memory impairment, whereas epsilon2 decreases these
      risks compared with the most common epsilon3 allele, but the mechanism for these
      effects is unknown. Long-term potentiation (LTP) is an experimentally induced
      increase in synaptic efficacy that models memory. Using hippocampal slices from
      wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing
      human apoE2, E3, or E4 (apoE-TR) we found that although all strains had
      comparable basal synaptic transmission, LTP was significantly greater in WT and
      apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to
      investigate the mechanisms of apoE isoform dependent modulation of susceptibility
      to memory impairment.

PMID- 15570173
TI  - Progesterone counteracts estrogen-induced increases in neurotrophins in the aged
      female rat brain.
AB  - Neurotrophin alterations have been associated with normal aging and age-related
      neurodegenerative disease, as well as cognitive status. Estrogen influences
      expression of mRNA and protein of neurotrophins and their receptors, and affects
      cognitive performance in young ovariectomized (Ovx) rats. The current
      investigation evaluated whether estrogen or estrogen plus progesterone affects
      neurotrophin protein levels in cognitive brain regions in the aged Ovx rat. While
      estrogen treatment increased BDNF, NGF, and NT3 levels in entorhinal cortex,
      progesterone abated the effects of estrogen resulting in neurotrophin levels
      comparable to aged Ovx rats not given hormone. Our findings suggest that the aged
      female brain is responsive to estrogen in cognitive brain regions, and that
      progesterone can reverse these estrogen effects.

PMID- 15570174
TI  - Control of hyperphagia prevents obesity in BDNF heterozygous mice.
AB  - Reduced levels of BDNF in mice cause obesity and behavioral abnormalities
      including increased aggression and hyperactivity. While it has been shown that
      the obesity is in part caused by increased food consumption it is still not clear
      whether defects in other mechanisms involved in the control of body weight
      homeostasis can also affect this phenotype. Here we report that mice with reduced
      levels of BDNF do not develop obesity and have normal blood glucose levels if fed
      over a prolonged period of time the amount of food that control mice usually
      consume. Thus, hyperphagia appears to be the primary cause of obesity development
      rather than changes in mechanisms controlling metabolism.

PMID- 15570175
TI  - Effects of co-activation on cortical organization and discrimination performance.
AB  - We used fMRI to investigate the effects of tactile co-activation on the
      topographic organization of the human primary somatosensory cortex (SI).
      Behavioral consequences of co-activation were studied in a psychophysical task
      assessing the mislocalization of tactile stimuli. Co-activation was applied to
      the index, middle and ring fingers of the right hand either synchronously or
      asynchronously. Cortical representations for synchronously co-activated fingers
      moved closer together, whereas cortical representations for asynchronously co
      activated fingers became segregated. Behaviorally, this pattern coincided with an
      increased and reduced number of mislocalizations between synchronously and
      asynchronously co-activated fingers, respectively. Thus, both synchronous and
      asynchronous coupling of passive tactile stimulation is able to induce short-term
      cortical reorganization associated with functionally relevant changes.

PMID- 15570176
TI  - NPY mediates the feeding elicited by muscimol injections into the nucleus
      accumbens shell.
AB  - Injections of muscimol into the nucleus accumbens shell (AcbSh) induce large
      increases in food intake in satiated rats and also activate neurons in a number
      of feeding-related brain regions, including NPY-containing neurons in the arcuate
      hypothalamic nucleus and cells in the paraventricular hypothalamic nucleus. This
      suggests that the NPY system may participate in the expression of AcbSh-mediated
      feeding behavior. Therefore, we examined the effects of intraventricular
      administration of the Y1 receptor antagonist 1229U91 or the Y5 receptor
      antagonist L-152,804 on AcbSh-mediated food intake. Intra-AcbSh muscimol elicited
      a large increase in food intake which was potently suppressed by blocking either
      central Y1 or Y5 receptors. Our results suggest that the AcbSh influences food
      intake, in part, through the release of NPY.

PMID- 15570177
TI  - A novel neurotrophic peptide: APP63-73.
AB  - The objective of this study was to find out which N-terminal segment/s of amyloid
      precursor protein (APP) has any neurotrophic properties, since soluble APP-alpha
      (sAPP-alpha) has neurotrophic effects. We investigated neurotrophic properties of
      eight peptide segments of N-terminal APP. The APP63-73 was able to enhance
      neuronal growth; augment axonal and cell body growth in human neuroblastoma cell
      line, SH-SY5Y. Neurotrophic effects of chronic APP63-73 treatment were assessed
      in vivo using streptozotocin-induced diabetes and ovariectomized rats. Thus, this
      study demonstrated that APP63-73 peptide has neurotrophic effects both in vivo
      and in vitro.

PMID- 15570178
TI  - Sleep EEG dynamics in rat barrel cortex associated with sensory deprivation.
AB  - Sleep is involved in the development and maintenance of neural networks. We
      investigated how somatosensory deprivation affects EEG dynamics of adult rats
      during sleep, which might be a result of changes in neural organization. Rats'
      whiskers were clipped unilaterally daily and the resulting changes in the balance
      of EEG spectral powers between the intact and sensory deprived barrel cortices
      were recorded for a month. Both delta and theta band spectral powers in the
      deprived cortex initially decreased in terms of their ratio to the intact cortex.
      Subsequently, the ratio was restored to control levels. This non-monotonic change
      in EEG activity might reflect the re-organization process of the cortical
      circuit.

PMID- 15570179
TI  - Metabotropic glutamate receptors contribute to neocortical synaptic plasticity in
      vivo.
AB  - Metabotropic glutamate receptors (mGluRs) have been shown to be important for
      hippocampus-dependent memory, as well as activity-dependent synaptic plasticity
      in the hippocampus. In this study, we examined the role of mGluRs in the
      induction of two forms of activity-dependent synaptic plasticity, long-term
      potentiation (LTP) and long-term depression (LTD), in the neocortex of awake,
      freely-moving rats. The mGluR antagonist AIDA was administered during the
      induction of LTP or LTD in the motor cortex. There was a 50% reduction of LTP
      induced in the early component of the evoked response, but there was no effect on
      the late component and no effect on the induction of LTD. Thus, mGluRs contribute
      to at least one form of activity dependent synaptic plasticity in the neocortex.

PMID- 15570180
TI  - Overview of FTY720 clinical pharmacokinetics and pharmacology.
AB  - Drug discovery programs are actively exploring for therapeutic agents targeting
      enzymes and receptors regulating sphingolipid metabolism and biologic functions.
      FTY720 is a close structural analogue of sphingosine with immunomodulatory
      properties. After oral administration, FTY720 is phosphorylated by sphingosine
      kinase to form the active moiety FTY720-phosphate, which subsequently binds to
      the sphingosine-1-phosphate receptor. In characterizing the safety and
      pharmacological effects of FTY720, detailed clinical pharmacology studies in
      healthy subjects and renal transplant recipients have focused on cardiac
      responses and lymphocyte trafficking. After the first dose, FTY720 causes a mild,
      transient decrease in heart rate that returns to baseline in approximately 1 to 2
      weeks despite continued administration of the drug. FTY720 elicits a prompt and
      dose-dependent decrease in peripheral blood lymphocytes by redirecting them from
      the circulation to the lymph nodes without impairing lymphocyte functions. An
      association among FTY720 blood concentration, decrease in lymphocyte counts, and
      freedom from acute rejection episodes has been observed in early clinical
      development trials in de novo kidney transplantation.

PMID- 15570181
TI  - Pharmacodynamics in the development of new immunosuppressive drugs.
AB  - Over the past 10-20 years a number of immunosuppressive drugs, such as
      cyclosporine A, tacrolimus, sirolimus, or mycophenolate mofetil have been
      approved for clinical use and have been highly successful in preventing or
      delaying graft rejection. Nevertheless, there is an incessant need for better and
      safer drugs to improve short-term and long-term outcomes following
      transplantation. A number of low-molecular-weight molecules that interfere with
      immune cell functions are in development. These include molecules that inhibit
      the janus protein tyrosine kinase JAK3, compounds that alter lymphocyte
      trafficking (the sphingosine-1-phosphate receptor antagonist FTY720), and new
      malononitrilamides (FK778). All seem to show promising therapeutic potential.
      Among the biologic agents, there are high expectations for antibodies or
      recombinant chimeric molecules targeting costimulatory surface molecules or
      pathways involved in the migration of immune cells. The list of such targets
      includes the ligand pairs CD28:B7, CD154:CD40, LFA-1:ICAM-1, ICOS:B7RP-1, and VLA
      4:VCAM-1. However, the clinical development of drugs for transplantation has
      proved to be difficult, complex, and time consuming. Therefore, newly emerging
      drug candidates will also demand better methods for monitoring their efficacy as
      well as their side effects in vivo. Pharmacokinetics (PK) and pharmacodynamics
      (PD) are complementary approaches used to select drugs on the basis of their in
      vivo efficacy as well as safety. Whereas PK monitors the handling of the drug by
      the body, PD focuses on the biologic effect of the drug on its target. Therefore,
      PD studies of in vivo efficacy are useful for clinical decisions to determine the
      optimal dose and type of immunosuppressant. At the preclinical stage, PD is aimed
      at accelerating the selection of lead compounds via PD-controlled trials in
      animals. Moreover, PD can help to discover new mechanisms of action for a drug or
      a drug candidate. However, its full potential has not been used, mainly because
      of laborious and time-consuming methodology. This review focuses on established
      and novel PD/PK approaches to assess immunosuppressive compounds in the context
      of new evolving drugs or drug combinations.

PMID- 15570182
TI  - Sampling times for monitoring tacrolimus in stable adult liver transplant
      recipients.
AB  - The aim of this study was to determine the most informative sampling time(s)
      providing a precise prediction of tacrolimus area under the concentration-time
      curve (AUC). Fifty-four concentration-time profiles of tacrolimus from 31 adult
      liver transplant recipients were analyzed. Each profile contained 5 tacrolimus
      whole-blood concentrations (predose and 1, 2, 4, and 6 or 8 hours postdose),
      measured using liquid chromatography-tandem mass spectrometry. The concentration
      at 6 hours was interpolated for each profile, and 54 values of AUC(0-6) were
      calculated using the trapezoidal rule. The best sampling times were then
      determined using limited sampling strategies and sensitivity analysis. Linear
      mixed-effects modeling was performed to estimate regression coefficients of
      equations incorporating each concentration-time point (C0, C1, C2, C4,
      interpolated C5, and interpolated C6) as a predictor of AUC(0-6). Predictive
      performance was evaluated by assessment of the mean error (ME) and root mean
      square error (RMSE). Limited sampling strategy (LSS) equations with C2, C4, and
      C5 provided similar results for prediction of AUC(0-6) (R2 = 0.869, 0.844, and
      0.832, respectively). These 3 time points were superior to C0 in the prediction
      of AUC. The ME was similar for all time points; the RMSE was smallest for C2, C4,
      and C5. The highest sensitivity index was determined to be 4.9 hours postdose at
      steady state, suggesting that this time point provides the most information about
      the AUC(0-12). The results from limited sampling strategies and sensitivity
      analysis supported the use of a single blood sample at 5 hours postdose as a
      predictor of both AUC(0-6) and AUC(0-12). A jackknife procedure was used to
      evaluate the predictive performance of the model, and this demonstrated that
      collecting a sample at 5 hours after dosing could be considered as the optimal
      sampling time for predicting AUC(0-6).

PMID- 15570183
TI  - Characterization of a phase 1 metabolite of mycophenolic acid produced by
      CYP3A4/5.
AB  - To characterize a phase 1 metabolite of mycophenolic acid (MPA) and the human
      cytochrome P450 isoform(s) (CYP) involved in its formation. MPA metabolites were
      investigated in blood and urine samples from transplant patients under
      mycophenolate mofetil therapy (n = 5) as well as with in vitro incubation of MPA
      with human liver microsomes. The CYP isoforms involved in the oxidative
      metabolism were investigated in vitro on human liver microsomes with isoform
      specific inhibitors as well as in human embryonic kidney cell lines expressing
      recombinant human CYPs. The analytic methods used were based on LC-MS/MS. A 6-O
      desmethyl-MPA (DM-MPA) metabolite and 2 related glucuronides were identified in
      patients' blood and urine. Human liver microsomes produced DM-MPA with an
      apparent Km = 0.83 +/- 0.06 mmol/L and Vmax = 5.57 +/- 0.29 pmol/mg/min. The
      CYP3A inhibitor ketoconazole was found to inhibit DM-MPA formation by 50.3% with
      respect to the control, and trimethoprim (CYP2C8 inhibitor) reduced it by 30.1%.
      However, DM-MPA was produced only by the transfected cell lines expressing CYP3A4
      and, to a lesser extent, CYP3A5. In vitro, MPA at concentrations above the plasma
      therapeutic range was found to decrease the metabolism of tacrolimus, suggesting
      a possible competition for CYP3A. No effect of MPAat therapeutic or higher level
      was found on cyclosporin metabolism. The phase 1 metabolite of MPA previously
      known as M-3 was identified as 6-O-desmethyl-MPA and is produced by CYP3A4/5 and
      probably CYP2C8. MPA might compete with other drugs on CYP3A because of its high
      therapeutic concentrations, although this was not the case for cyclosporin and to
      only a small extent for tacrolimus.

PMID- 15570184
TI  - Comparison of liquid chromatography-tandem mass spectrometry with a commercial
      enzyme-multiplied immunoassay for the determination of plasma MPA in renal
      transplant recipients and consequences for therapeutic drug monitoring.
AB  - Mycophenolic acid (MPA) is an immunosuppressive drug partly metabolized to MPA
      glucuronide (MPAG), which is pharmacologically inactive. The currently available
      enzyme-multiplied immunoassay technique (EMIT) has been reported to overestimate
      MPA plasma concentration in clinical samples when compared with HPLC techniques.
      The aims of this study were to design and validate a specific liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) technique for the
      determination of MPA and MPAG using a low plasma volume and a simple sample
      preparation procedure; then to compare it with EMIT for the determination of MPA
      in plasma samples collected over an interdose interval at different
      posttransplantation periods (days 3, 7, and 30 and after 3 months) in 25 renal
      transplant recipients orally administered cyclosporine and mycophenolate mofetil
      twice daily, to investigate the origins of the differences between techniques.
      The LC-MS/MS technique developed showed limits of quantification (LOQs) of 0.1
      mg/L and 1 mg/L for MPA and MPAG, respectively, and was linear, accurate, and
      precise from these LOQs up to 30 mg/L for MPA and 300 mg/L for MPAG. EMIT gave
      similar results to LC-MS/MS for spiked quality control samples (in a synthetic
      matrix or in drug-free plasma) but significantly overestimated MPA levels in
      clinical samples: EMIT - LC-MS/MS = +61.39% +/- 57.94%, with large variations
      depending on patients, time elapsed since transplantation, sampling time, and
      concentration levels. These results confirmed the known overestimation of the
      EMIT assay compared with a specific method and showed that the magnitude of this
      overestimation depended on sampling time and time after transplantation.

PMID- 15570185
TI  - Mycophenolic acid in diabetic renal transplant recipients: pharmacokinetics and
      application of a limited sampling strategy.
AB  - Limited sampling strategies may be useful in optimizing therapeutic drug
      monitoring of mycophenolic acid (MPA). Their use, however, may be limited by
      several patient factors, including comorbidity. In this study the
      pharmacokinetics of MPA in diabetic and nondiabetic renal transplant recipients
      were compared, and it was evaluated whether a limited sampling strategy developed
      and validated for nondiabetic patients can also be used in diabetic patients. The
      pharmacokinetics of MPA were analyzed on days 7 and 11 after transplantation in
      136 renal transplant patients, among whom 7 patients had diabetes. All patients
      received cyclosporine and corticosteroids as maintenance immunosuppressive
      therapy. A limited sampling strategy [AUC (mg x h/L) = 7.182 + 4.607 C0 + 0.998
      C0.67 + 2.149 C2] was developed and validated for nondiabetic patients and was
      subsequently tested for its usefulness in diabetic patients. Diabetic renal
      transplant patients did not have significantly different dose-normalized MPA area
      under concentration-time curve (AUC), MPA clearance, or MPA maximum concentration
      (Cmax). However, in diabetic patients Tmax (time of Cmax, 1.59 hours) was higher
      than for nondiabetic patients (0.67 hours) on day 11 (P = 0.04). The developed
      and validated limited sampling strategy performed acceptably, estimating MPA AUC
      in nondiabetic patients with a mean bias of 0.2 mg x h/L (95% confidence interval
      from -1.3 to 1.6 mg x h/L). Applying the limited sampling strategy in diabetic
      patients revealed a mean bias of -1.5 (-5.7, 2.7 mg x h/L). In conclusion,
      although diabetic renal transplant patients exhibit increased Tmax, this does not
      affect the accuracy of the limited sampling strategy.

PMID- 15570186
TI  - Long-term follow-up using a higher target range for lamotrigine monitoring.
AB  - The aims of the study were (1) to review the clinical application of the higher
      target plasma lamotrigine (LTG) concentration of 3-14 mg/L previously proposed by
      our therapeutic drug monitoring (TDM) laboratory following our initial study 7
      years earlier, and (2) to survey clinical application of LTG assays by
      experienced neurologists (n = 11) who frequently use LTG. There was a 2.9-fold
      increase in LTG assay requests received by our laboratory from 1996 to 2003. By
      comparison, data for the number of LTG prescriptions filled throughout Australia
      were limited to the 4 years from 1997 to 2000, where a 1.7-fold increase was
      seen. LTG assay requests increased 1.5-fold in this same 4-year period (r2 =
      0.97), indicating that the growth in assay requests paralleled the growth in
      prescriptions. The distribution of LTG concentrations measured in 2003 was
      compared with those for 1996 and 1997. This indicated there was a significantly
      increased (P < 0.01) clinical usage of the higher LTG target range. This result
      was reinforced by questionnaire responses. Respondents (100% of those surveyed),
      (1) considered the target LTG concentration (3-14 mg/L) to be one of the primary
      parameters applied in individualizing LTG dosage regimens, (2) were using target
      concentrations above 7 mg/L in 75% of patients, and (3) reported dose-limiting
      toxicities in some (but not all) patients typically at concentrations above, or
      well above, 13 mg/L. In conclusion, the growth in LTG assay requests received by
      our laboratory paralleled prescribing of this drug. The clinical use of the
      higher LTG target concentration range was increased during the 7 years since its
      introduction, indicating clinical acceptance and therapeutic benefit as well as
      the absence of long-term adverse effects associated with higher plasma LTG
      concentrations.

PMID- 15570187
TI  - Association between patient age and gabapentin serum concentration-to-dose ratio:
      a preliminary multivariate analysis.
AB  - OBJECTIVES: To evaluate the association between patient age and gabapentin (GBP)
      concentration-to-dose ratio by a multivariate analysis. METHODS: The association
      between patient age and the trough steady-state serum concentration of gabapentin
      (GBP) normalized to 1 mg/kg body weight or concentration-to-dose ratio (CDR) was
      retrospectively assessed by analysis of covariance. Potential confounding factors
      considered were GBP dosage, the number of GBP doses per day, and the presence of
      concomitant antiepileptic drugs (AEDs). Concentrations that had been measured in
      predose "trough" samples collected from 66 patients, aged 5-84 years, with
      partial seizures or neuropathic pain chronically receiving GBP BID (n = 21) or
      TID (n = 45), alone (n = 15) or in combination with other AEDs (n = 51) were used
      in this retrospective analysis. RESULTS: Average GBP CDR was 0.23 +/- 0.18 (mean
      +/- SD). The GBP CDR increased with age (r2 = 0.46, P < 0.001), and the
      correlation was improved when only samples from patients taking GBP BID were
      separately considered (r2 = 0.68, P < 0.001). The ratio was lower in the 10
      children younger than 11 years of age (0.07 +/- 0.05) than in 8 adolescents aged
      12 to 18 years (0.14 +/- 0.04), lower than in 35 adults aged 19 to 65 years (0.22
      +/- 0.13), and lower than in 13 patients older than 65 years of age (0.45 +/-
      0.20) by 1-way analysis of variance (F = 19.4, P < 0.001). Analysis of covariance
      showed a significant influence on GBP CDR of patient age (P < 0.001) and the
      number of GBP daily doses (P < 0.01), but GBP daily dosage or concomitant AEDs
      had no significant influence on the ratio. CONCLUSIONS: In this retrospective
      study of a small, select group of patients, (1) the GBP CDR increased
      significantly with age when potential confounding factors such as GBP dosage,
      number of GBP doses per day, and concomitant AEDs were considered by analysis of
      covariance, and (2) patients older than 65 years, even without any known renal
      disease, may have double GBP CDR than younger adults and, therefore, may need
      half of the GBP dose per body weight to achieve a similar concentration.

PMID- 15570188
TI  - Effects of concomitant fluvoxamine on the plasma concentration of etizolam in
      Japanese psychiatric patients: wide interindividual variation in the drug
      interaction.
AB  - Administration of fluvoxamine with concomitant benzodiazepines is common in
      clinical situations. This study investigated the effects of the coadministration
      of fluvoxamine on plasma concentrations of etizolam and evaluated the effects of
      various fluvoxamine doses on drug interactions with etizolam. Subjects were 18
      Japanese outpatients concomitantly treated with fluvoxamine before or after
      monotherapy with etizolam. Plasma concentrations of etizolam were measured using
      a column-switching high-performance liquid chromatographic method with
      ultraviolet detection. In 17 subjects treated concomitantly with fluvoxamine at
      25 mg or 50 mg, the ranges of plasma concentrations of etizolam corrected for the
      dose increased from 2.0-13.3 (mean 6.3 +/- 3.6, n = 17) in monotherapy to 2.7
      18.2 (mean 9.6 +/- 5.1, n = 17) ng/mL/mg in concomitant doses. Wide variations
      were observed in the drug interactions; however, coadministration with
      fluvoxamine produced significant changes in the plasma concentrations of etizolam
      (P < 0.0001) with a median of 42.9% (range 0.0 to 235.0%). Although the
      sleepiness of the subjects was evaluated using the Stanford Sleepiness Scale, no
      changes in sleepiness were found between the etizolam-monotherapy and the
      fluvoxamine-concomitant states. Of the 12 subjects treated concomitantly with
      fluvoxamine at 25 mg, 2 subjects received fluvoxamine at a dose increased up to
      150 mg, and another received fluvoxamine at a dose increased up to 200 mg. They
      showed an increase in the plasma concentrations of etizolam in a fluvoxamine dose
      dependent manner; more particularly, the increased dose of fluvoxamine (150 mg
      and 200 mg) resulted in about a twofold variation in plasma concentrations of
      etizolam.

PMID- 15570189
TI  - Midazolam therapeutic drug monitoring in intensive care sedation: a 5-year
      survey.
AB  - During a 5-year period, 1997 to 2002, therapeutic drug monitoring of midazolam
      plasma concentrations in combination with the level of sedation as assessed by
      the Ramsay sedation scale was performed in 648 critically ill patients requiring
      artificial ventilation. In a subgroup of 189 patients sepsis-related organ
      failure assessment procedure was additionally performed. A total number of 3354
      samples were analyzed. Significantly reduced clearance of midazolam was observed
      within the first 4 days of midazolam treatment of critically ill patients. As a
      result, accumulation of midazolam and its metabolites occurred within the first
      week of treatment. In contrast, parameters such as serum bilirubin or creatinine,
      which are commonly used to adapt drug therapy to organ dysfunction, showed
      significant changes with a delay of more than 10 days as compared with the
      findings of midazolam monitoring. Midazolam plasma concentrations showed a good
      correlation with the sedative capacity of the drug (r2 = 0.906). However, a great
      variability of the drug effect between patients could be demonstrated, which, as
      a consequence, may complicate the development of dosing strategies based on
      midazolam plasma concentrations to better control sedation in critically ill
      patients. Furthermore, patient age seems to be an important factor for the
      considerable variability of the sedative effect of midazolam. To achieve a
      certain levels of sedation, significantly lower midazolam infusion rates as well
      as plasma concentrations were required as the patients age increased. No
      significant sex-related differences could be observed for any pharmacologic
      parameter obtained in this study. Our findings suggest that midazolam therapeutic
      drug monitoring might be a useful tool to individualize midazolam therapy,
      especially in critically ill patients developing organ dysfunction and requiring
      long-term sedation to minimize the risk of drug accumulation and excessive
      sedation.

PMID- 15570190
TI  - Validation of an assay for voriconazole in serum samples using liquid
      chromatography-tandem mass spectrometry.
AB  - A simple and rapid liquid chromatography tandem mass spectrometry (HPLC-MS/MS)
      method for the analysis of voriconazole has been developed. For comparison, serum
      voriconazole was measured using HPLC and bioassay. For the HPLC-MS/MS assay,
      samples were prepared in a deep-well block by adding 10 microL of serum to 40
      microL of 0.1 M zinc sulfate solution. Proteins were precipitated by adding 100
      microL acetonitrile containing ketoconazole as internal standard. After vigorous
      mixing and centrifugation, 3 microL of the supernatant was injected into the HPLC
      MS/MS system. An HPLC system was used to elute a C18 cartridge (2 mm x 4 mm) at
      0.6 mL/min with a step gradient of 50% to 100% methanol containing 2 mM ammonium
      acetate and 0.1% (vol/vol) formic acid. The column was maintained at 55 degrees
      C, and the retention times were voriconazole 1.50 minutes and ketoconazole 1.47
      minutes. Cycle time was 3 minutes, injection to injection. The analytes were
      monitored using a tandem mass spectrometer operated in multiple reaction
      monitoring mode using the following transitions: voriconazole m/z 350.0 > 224.1
      and ketoconazole m/z 531.1 > 489.1. Within- and between-batch CVs were < 5% and <
      8%, respectively, over the range 0.38 to 15.3 mg/L. The lower limit of
      quantification was 0.1 mg/L. Regression analysis showed HPLC-MS/MS = 1.06 +/-
      0.02 (HPLC-UV) - 0.07 +/- 0.1, R2 = 0.95, n = 99.

PMID- 15570191
TI  - Rapid detection of oleander poisoning using digoxin immunoassays: comparison of
      five assays.
AB  - Oleander is an ornamental shrub that grows in the United States, Australia,
      India, Sri Lanka, China, and other parts of the world. All parts of the plant are
      poisonous because the presence of cardiac glycoside oleandrin. Despite its
      toxicity, oleander extract is used in folk medicines. Because of its structural
      similarity, oleandrin cross-reacts with the fluorescence polarization immunoassay
      (FPIA) for digoxin. We studied the potential of detecting oleandrin in serum
      using 5 common digoxin immunoassays (FPIA, MEIA, both from Abbott; Beckman
      digoxin assay on Synchron LX, Chemiluminescent assay, CLIA from Bayer
      Diagnostics) and a recently FDA-approved turbidimetric assay on the ADVIA 1650
      analyzer (Bayer). Aliquots of drug-free and digoxin-like immunoreactive
      substances (DLIS)-free serum pools were supplemented with ethanol extract of
      oleander leaves or oleandrin (Sigma Chemicals) in amounts expected in vivo after
      severe overdose. We observed significant apparent digoxin concentration with
      FPIA, Beckman, and the new turbidimetric assay (1 mL drug-free serum supplemented
      with 5.0 microL of oleander extract: apparent digoxin 2.36 ng/mL by the FPIA,
      0.32 ng/mL by the MEIA, 0.93 ng/mL by the Beckman, 0.82 ng/mL by the new
      turbidimetric assay). The CLIA showed no cross-reactivity. Similar observations
      were made when serum pools were supplemented with oleandrin. Because cross
      reactivity should be tested in the presence of the primary analyte, we
      supplemented serum pools prepared from patients receiving digoxin with oleander
      extract or oleandrin. The measured digoxin concentrations were falsely elevated
      with the FPIA, Beckman, and turbidimetric assays, the highest false elevation
      being observed with the FPIA. Surprisingly, apparent digoxin concentrations were
      falsely lowered when MEIA was used. Digibind neutralizes free apparent digoxin
      concentration in vitro in serum pools supplemented with oleander extract, and
      this effect can be measured by the FPIA. We conclude that FPIA is most sensitive
      to detect the presence of oleander in serum. In contrast, the CLIA (no cross
      reactivity) should be used for monitoring digoxin in a patient receiving digoxin
      and self-medicated with a herbal remedy containing oleander.

PMID- 15570192
TI  - Urinary pharmacokinetics of methamphetamine and its metabolite, amphetamine
      following controlled oral administration to humans.
AB  - Methamphetamine is widely abused for its euphoric effects. Our objectives were to
      characterize the urinary pharmacokinetics of methamphetamine and amphetamine
      after controlled methamphetamine administration to humans and to improve the
      interpretation of urine drug test results. Participants (n = 8) received 4 daily
      10-mg (low) oral doses of sustained-release (d)-methamphetamine hydrochloride
      within 7 days. After 4 weeks, 5 participants received 4 daily 20-mg (high) oral
      doses. All urine specimens were collected during the study. Methamphetamine and
      amphetamine were measured by GC-MS/PCI. Maximum excretion rates ranged from 403
      to 4919 microg/h for methamphetamine and 59 to 735 microg/h for amphetamine with
      no relationship between dose and excretion rate. The mean molar percentage of
      dose in the urine as total methamphetamine and amphetamine were 57.5 +/- 21.7%
      (low dose) and 40.9 +/- 8.5% (high dose). Mean urinary terminal elimination half
      lives across doses were 23.6 +/- 6.6 hours for methamphetamine and 20.7 +/- 7.3
      hours for amphetamine. Methamphetamine renal clearance across doses was 175 +/-
      102 mL/min. The mean amphetamine/methamphetamine percentage ratio based on the
      area under the urinary excretion-time curve increased over time from 13.4 +/-
      6.5% to 35.7 +/- 26.6%. Slow urinary excretion results in drug accumulation and
      increases in detection time windows. Our findings also support the presence of an
      active renal excretion mechanism for methamphetamine.

PMID- 15570193
TI  - Assessment of thiopurine methyltransferase and metabolite formation during
      thiopurine therapy: results from a large Swedish patient population.
AB  - This study examined thiopurine methyltransferase (TPMT) and the relationship to
      thioguanine nucleotides (TGN) and methylthioinosine monophosphate (meTIMP) in a
      large Swedish patient population. The current hypothesis is that the cytotoxic
      effects of thiopurine drugs are mediated by the incorporation of TGN into DNA.
      The authors assayed the TPMT activity in red blood cells from 1151 subjects and
      the concentrations of TGN (n = 602) and meTIMP (n = 593) from patients treated
      with thiopurine drugs. The TPMT frequency distribution in both adults and
      children showed some differences from what had been found in unselected general
      populations. Children had lower median TPMT activity than adults (12.0 versus
      12.9 U/mL RBC; P < 0.001). Relative differences in both TGN formation [medians:
      normal TPMT, 1.3; intermediate TPMT, 3.3; low TPMT, 47.9 pmol/8 x 10(8) RBC per
      mg azathioprine (AZA); P < 0.001] and meTIMP formation (medians: normal TPMT, 13;
      intermediate TPMT, 7.3; low TPMT, 0 pmol/8 x 10(8) RBC per mg AZA; P = 0.001) per
      1 mg administered drug were noted among the 3 TPMT activity groups. Women formed
      higher concentrations of both TGN (1.5 versus 1.3 pmol/8 x 10(8) RBC per mg AZA;
      P = 0.01) and meTIMP (14.4 versus 10.7 pmol/8 x 10(8) RBC per mg AZA; P = 0.01)
      than men did. There was a significant correlation between the AZA dose and the
      meTIMP concentrations (r = 0.45; P < 0.001). Furthermore, dose alterations made
      in subjects with normal TPMT (n = 84) and intermediate TPMT (n = 22) activity
      resulted in more pronounced increases in TGN concentrations (170 versus 30 pmol/8
      x 10(8) RBC; P < 0.001) in intermediate TPMT activity, whereas in normal TPMT
      activity changes in meTIMP concentrations were more pronounced (1.3 versus 0
      nmol/8 x 10(8) RBC; P < 0.001). In normal TPMT activity both metabolites
      increased in a dose-dependent fashion, whereas in intermediate TPMT activity only
      TGN concentrations increased. The results of this study demonstrate the dynamic
      nature of thiopurine metabolism and its importance for thiopurine dosing.

PMID- 15570194
TI  - Genotype and allele frequencies of C3435T polymorphism of the MDR1 gene in
      various Jewish populations of Israel.
AB  - The human multidrug-resistant gene (MDR1) encodes for P-glycoprotein (P-gp),
      which is a membrane-bound efflux-transporter conferring resistance to a number of
      natural cytotoxic drugs and potentially toxic xenobiotics. The wobble C3435T
      polymorphism at exon 26 was associated with different expression levels of the
      MDR1 gene and substrate uptake. Differences in allele frequencies of the C3435T
      polymorphism have previously been demonstrated between racial groups. In this
      study, 500 individuals from 5 Jewish populations of Israel (Ashkenazi, Yemenite,
      North African, Mediterranean, Near-Eastern) were examined for C3435T polymorphism
      using a PCR-RFLP-based technique to calculate genotype and allele frequencies.
      Frequencies of the C allele were quite similar among the Ashkenazi (0.65),
      Yemenite (0.645), and North-African (0.615) Jewish populations. However, the
      frequency of this allele was slightly lower among Mediterranean Jews (0.58) and
      significantly lower among Near-Eastern Jews (0.445). The frequency of the C
      allele among Near-Eastern Jews is, therefore, significantly different from those
      of all other tested Jewish populations. In comparison to previously studied non
      Jewish populations, the frequency of this allele among Near-Eastern Jews is
      different from that in West Africans (0.91) but is similar to that in whites
      (0.497). However, the C allele frequencies among the other 4 Jewish populations
      are significantly lower than that found among West Africans and significantly
      higher than among non-Jewish whites. These data may have important therapeutic
      and prognostic implication for P-gp-related drug dosage recommendation in Jewish
      populations.

PMID- 15570195
TI  - Severe adverse effects in a newborn with two defective CYP2D6 alleles after
      exposure to paroxetine during late pregnancy.
AB  - Paroxetine, like other SSRIs, is reported not to increase the number of
      malformations in infants exposed to these drugs in utero. However, late pregnancy
      exposure to SSRIs sometimes leads to perinatal complications resembling the
      symptoms seen in serotonergic overstimulation. We report here a case of third
      trimester paroxetine exposure with adverse birth outcome in a newborn. The
      clinical symptoms in the infant included severe tremor and rigidity as well as
      loose stools during the first 4 days of life. Plasma paroxetine concentrations in
      infant plasma were quite low after birth, but she was genotyped to be a poor
      metabolizer of CYP2D6, the enzyme catalyzing the metabolism of paroxetine. In
      accordance with an earlier report, we suggest that even low plasma concentrations
      of paroxetine may be related to perinatal complications in infants exposed to
      paroxetine during late pregnancy and that the poor metabolizer genotype of CYP2D6
      may be a risk factor for these complications.

PMID- 15570196
TI  - Accidental intravenous colchicine poisoning.
AB  - Colchicine is a commonly used drug for the treatment of gout and other
      indications. Toxicity from intentional oral overdoses of colchicine has been
      reported. Two cases are reported here in which colchicine was given by
      intravenous injection, and patients presented with multiorgan toxicity. The
      authors tested plasma and urine colchicine levels in these patients and found
      them significantly elevated. Testing of the vial from which the colchicine
      injections were given showed that the vial was mislabeled and contained 10-fold
      greater concentration of drug than the labeling indicated. These patients thus
      received a bolus dose of 20 mg of intravenous colchicine rather than the intended
      2-mg dose. An intravenous dose of this magnitude has not previously been
      reported.

PMID- 15570197
TI  - Distribution of diazepam between plasma and whole blood.

PMID- 15570198
TI  - General surgery as education, not specialization.

PMID- 15570199
TI  - One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in
      melanoma patients with multiple in-transit metastases.
AB  - OBJECTIVE: The aim of this study is to describe the experience with 100 TNF-based
      ILP for locally advanced melanoma and to determine prognostic factors for
      response, time to local progression, and survival. METHODS: One hundred TNF-based
      ILPs were performed between 1991 and 2003 in 87 patients for whom local control
      by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac,
      33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions
      with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume.
      RESULTS: Overall response was 95%, with 69% complete response, 26% partial
      response, and 5% no change. Complete response rate differed significantly for
      patients with IIIA disease versus IIIAB and IV. Local and systemic toxicity was
      mild to moderate in almost all cases, with no treatment-related death and one
      treatment-related amputation. Five-year overall survival was 32%; local
      progression occurred in 55% after a median of 16 months. In complete response
      patients, 5-year survival was 42% with local progression in 52% at a median of 22
      months. Response rate and survival were significantly influenced by stage of
      disease; (local progression free) survival was influenced by response rate.
      CONCLUSIONS: TNF-based ILP results in excellent response rates in this patient
      population with unfavorable characteristics. Response on ILP predicts outcome in
      patients and reflects aggressiveness of the tumor.

PMID- 15570200
TI  - Surgical management of primary hyperparathyroidism: the case for giving up quick
      intraoperative PTH assay in favor of routine PTH measurement the morning after.
AB  - OBJECTIVE: To analyze the utility of quick intraoperative parathyroid hormone
      (PTH) measurement in the surgical management of primary hyperparathyroidism.
      BACKGROUND DATA: The use of intraoperative PTH monitoring is well established in
      the surgery of primary hyperparathyroidism. However, some false-negative
      predictions lead to unnecessary explorations; furthermore, surgeons are becoming
      increasingly dependent on hormone measurement for intraoperative decisions, which
      raises concerns about the cost-effectiveness of the method. METHODS: A
      retrospective analysis of 268 neck explorations performed for primary
      hyperparathyroidism using intraoperative PTH monitoring from April 2001 to
      February 2003 was done. We used the criterion of "biologic recovery" of
      hyperfunctioning tissue, defined as a more than 50% decrease in PTH level from
      baseline value at 5 minutes after excision to predict the outcome of successful
      parathyroidectomy documented by normal postoperative serum calcium level.
      Additionally, we also sampled PTH at 10 minutes, 30 minutes, and the morning
      after surgery to compare the predictive value of delayed sampling. Patients were
      classified according to the prediction being concordant or discordant with the
      outcome. The data were analyzed using a 2 x 2 table construct for each of the
      sampling times, therefore providing sequential sensitivity, specificity, positive
      and negative predictive values, and overall accuracy of the predictions. RESULTS:
      Concordance or overall accuracy of prediction (true positives and negatives) was
      obtained in 229 cases (85.4%), and discordance or failure of prediction (false
      positives and negatives) was obtained in 34 cases (12.7%) at T5. On analyzing the
      iPTH prediction at T10, T30, and D1 among the group of 33 false negatives, we
      found that 28 (10.4%) patients reached the concordance at 30 minutes, while by
      the first day 32 patients (12.3%) had achieved concordance. Thus, there was a
      progressive increase in sensitivity and overall accuracy, but more importantly,
      in the negative predictive value reaching 88.9% on the day after surgery.
      CONCLUSIONS: The method of sampling PTH intraoperatively at 5 minutes has a high
      positive predictive value (99.5%) but a low negative predictive value (19.5%),
      which can lead to unnecessary explorations and a delay in the operative
      procedure. The negative predictive value increases substantially at 30 minutes
      and is best on the day after surgery. We suggest giving up the intraoperative
      measurement of PTH to adopt the first day postoperative measurement of PTH as a
      predictor of successful parathyroidectomy.

PMID- 15570201
TI  - The role of antibiotic prophylaxis in prevention of wound infection after
      Lichtenstein open mesh repair of primary inguinal hernia: a multicenter double
      blind randomized controlled trial.
AB  - OBJECTIVE: To determine whether the use of prophylactic antibiotics is effective
      in the prevention of postoperative wound infection after Lichtenstein open mesh
      inguinal hernia repair. SUMMARY BACKGROUND DATA: A recent Cochrane meta-analysis
      (2003) concluded that "antibiotic prophylaxis for elective inguinal hernia repair
      cannot be firmly recommended or discarded." METHODS: Patients with a primary
      inguinal hernia scheduled for Lichtenstein repair were randomized to a
      preoperative single dose of 1.5 g intravenous cephalosporin or a placebo.
      Patients with recurrent hernias, immunosuppressive diseases, or allergies for the
      given antibiotic were excluded. Infection was defined using the Centers for
      Disease Control and Prevention criteria. RESULTS: We included 1040 patients in
      the study between November 1998 and May 2003. According to the intention-to-treat
      principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the
      antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There
      was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo
      group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19%
      (95% confidence interval, -1.78%-1.40%) and a number needed to treat of 520 for
      the total number of infections. For deep infection, the absolute risk reduction
      is 0.20% (95% confidence interval, -0.87%-0.48%) with a number needed to treat of
      508. CONCLUSIONS: A low percentage (1.7%) of wound infection after Lichtenstein
      open mesh inguinal (primary) hernia repair was found, and there was no difference
      between the antibiotic prophylaxis or placebo group. The results show that, in
      Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not
      indicated in low-risk patients.

PMID- 15570202
TI  - Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal
      junction in 174 R0 resections: impact on staging, disease-free survival, and
      outcome: a plea for adaptation of TNM classification in upper-half esophageal
      carcinoma.
AB  - OBJECTIVE: To determine the impact of esophagectomy with 3-field lymphadenectomy
      on staging, disease-free survival, and 5-year survival in patients with carcinoma
      of the esophagus and gastroesophageal junction (GEJ). BACKGROUND: Esophagectomy
      with 3-field lymphadenectomy is mainly performed in Japan. Data from Western
      experience with 3-field lymphadenectomy are scarce and dealing with relatively
      small numbers. As a result, its role in the surgical practice of cancer of the
      esophagus and GEJ remains controversial. METHODS: Between 1991 and 1999, primary
      surgery with 3-field lymphadenectomy was performed in 192 patients, of whom a
      cohort of 174 R0 resections was used for further analysis. RESULTS: Hospital
      mortality of the whole series was 1.2%. Overall morbidity was 58%. Pulmonary
      complications occurred in 32.8%, cardiac dysrhythmias in 10.9%, and persistent
      recurrent nerve problems in 2.6%. pTNM staging was as follows: stage 0, 0.6%;
      stage I, 9.2%; stage II, 27.6%; stage III, 28.7%; and stage IV, 33.9%. Overall 3-
      and 5-year survival was 51% and 41.9%, respectively. The 3- and 5-year disease
      free survival was 51.4% and 46.3%, respectively. Locoregional lymph node
      recurrence was 5.2%; no patient developed an isolated cervical lymph node
      recurrence. Five-year survival for node-negative patients was 80.2% versus 24.5%
      for node-positive patients. Five-year survival by stage was 100% in stages 0 and
      I, 59.1% in stage II, 36.8% in stage III, and 13.3% in stage IV. Twenty-three
      percent of the patients with adenocarcinoma (25.8% distal third and 17.6% GEJ)
      and 25% of the patients with squamous cell carcinoma (26.2% middle third) had
      positive cervical nodes resulting in a change of pTNM staging specifically
      related to the unforeseen cervical lymph node involvement in 12%. Cervical lymph
      node involvement was unforeseen in 75.6% of patients with cervical nodes at
      pathologic examinations. Five-year survival for patients with positive cervical
      nodes was 27.7% for middle third squamous cell carcinoma. For distal third
      adenocarcinomas, 4-year survival was 35.7% and 5-year survival 11.9%. No GEJ
      adenocarcinoma with positive cervical nodes survived for 5 years. CONCLUSIONS:
      Esophagectomy with 3-field lymph node dissection can be performed with low
      mortality and acceptable morbidity. The prevalence of involved cervical nodes is
      high, regardless of the type and location of tumor resulting in a change of final
      staging specifically related to the cervical field in 12% of this series. Overall
      5-year and disease-free survival after R0 resection of 41.9% and 46.3%,
      respectively, may indicate a real survival benefit. A 5-year survival of 27.2% in
      patients with positive cervical nodes in middle third carcinomas indicates that
      these nodes should be considered as regional (N1) rather than distant metastasis
      (M1b) in middle third carcinomas. These patients seem to benefit from a 3-field
      lymphadenectomy. The role of 3-field lymphadenectomy in distal third
      adenocarcinoma remains investigational.

PMID- 15570203
TI  - Laparoscopic gastric bypass is superior to laparoscopic gastric banding for
      treatment of morbid obesity.
AB  - OBJECTIVE: To define whether laparoscopic gastric banding or laparoscopic Roux-en
      Y gastric bypass represents the better approach to treat patients with morbid
      obesity. SUMMARY BACKGROUND DATA: Two techniques, laparoscopic gastric bypass or
      gastric banding, are currently widely used to treat morbid obesity. Since both
      procedures offer certain advantages, a strong controversy exists as to which
      operation should be proposed to these patients. Therefore, data are urgently
      needed to identify the best therapy. METHODS: Since randomized trials are most
      likely not feasible because of the highly different invasiveness and
      irreversibility of these procedures, a matched-pair design of a large
      prospectively collected database appears to be the best method. Therefore, we
      used our prospective database including 678 bariatric procedures performed at our
      institution since 1995. A total of 103 consecutive patients with laparoscopic
      gastric bypass were randomly matched to 103 patients with laparoscopic gastric
      banding according to age, body mass index, and gender. RESULTS: Both groups were
      comparable regarding age, gender, body mass index, excessive weight, fat mass,
      and comorbidites such as diabetes, heart disease, and hypertension. Feasibility
      and safety: All gastric banding procedures were performed laparoscopically, and
      one gastric bypass operation had to be converted to an open procedure. Mean
      operating time was 145 minutes for gastric banding and 190 minutes for gastric
      bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days
      for gastric bypass. The incidence of early postoperative complications was not
      significantly different, but late complications were significantly more frequent
      in the gastric banding group (pouch dilatation). There was no mortality in both
      groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m in the
      gastric banding group and from 47.8 to 31.9 kg/m in the gastric bypass group
      within 2 years of surgery. These differences became significant from the first
      postoperative month until the end of the follow-up (24 months). The gastric
      bypass procedure achieved a significantly better reduction of comorbidities.
      CONCLUSIONS: Laparoscopic gastric banding and laparoscopic gastric bypass are
      feasible and safe. Pouch dilatations after gastric banding are responsible for
      more late complications compared with the gastric bypass. Laparoscopic gastric
      bypass offers a significant advantage regarding weight loss and reduction of
      comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y
      gastric bypass appears to be the therapy of choice.

PMID- 15570204
TI  - Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal
      pouch anal anastomosis: a randomized trial.
AB  - OBJECTIVE: The aim of the study was to evaluate postoperative recovery after hand
      assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal
      anastomosis for ulcerative colitis and familial adenomatous polyposis in a
      randomized controlled trial. METHODS: Sixty patients were randomized for hand
      assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome
      parameter was postoperative recovery in the 3 months after surgery, measured by
      quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were
      postoperative morphine requirement and surgical parameters, viz. operating time,
      morbidity, hospital stay, and costs. RESULTS: There was no difference between the
      2 procedures in quality of life assessment in the 3 months after surgery. There
      was a significant decline in quality of life on all scales of the SF-36 (P <
      0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no
      significant difference between the groups). Quality of life returned to baseline
      levels after 4 weeks. Operating times were longer in the laparoscopic group
      compared with the open group (210 and 133 minutes, respectively; P < 0.001). No
      significant differences were found in morphine requirement. Neither morbidity nor
      postoperative hospital stay differed between the laparoscopic and open group (20%
      versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728
      for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P
      = 0.095). CONCLUSIONS: Recovery measured using quality of life questionnaires is
      comparable for hand-assisted laparoscopic or open restorative proctocolectomy
      with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more
      costly than the open procedure.

PMID- 15570205
TI  - Mode of spread in the early phase of lymphatic metastasis in pancreatic ductal
      adenocarcinoma: prognostic significance of nodal microinvolvement.
AB  - BACKGROUND: The aim of this study was to assess the prognostic significance of
      nodal microinvolvement as well as the mode of spread in the early phase of
      lymphatic metastasis in patients with node-negative pancreatic ductal
      adenocarcinoma. METHODS: Lymph nodes from 48 node-negative patients with R0
      resected pancreatic ductal adenocarcinoma were sampled from 3 different
      compartments: 1) distal hepatoduodenal ligament, 2) superior-anterior
      compartment, and 3) posterior-inferior. Tissue sections of 148 lymph nodes
      classified as tumor free by routine histopathology were examined, using a
      sensitive immunohistochemical assay with the antiepithelial monoclonal antibody
      Ber-EP4 for tumor cell detection. With regard to histopathologic tumor staging
      and grading, 26 (54.2%) of the patients were staged as pT1/pT2, 22 (45.8%) as
      pT3/pT4, while 31 (64.6%) as G1/G2 and 17 (35.4%) patients as G3. Of the 148
      "tumor free" lymph nodes, 56 contained Ber-EP4-positive tumor cells. These 56
      lymph nodes were from 28 of the 48 patients. The multivariate Cox regression
      analysis revealed the independent prognostic impact of nodal microinvolvement on
      relapse-free and overall survival. Analysis by compartment, from which the lymph
      nodes were collected, revealed that overall survival time (P = 0.006) and time to
      local recurrence (P = 0.015) depend on the presence of nodal microinvolvement in
      the superior-anterior compartment. CONCLUSIONS: The influence of occult tumor
      cell dissemination in lymph nodes of patients with histologically proven
      pancreatic ductal adenocarcinoma supports the need for further tumor staging
      through immunohistochemistry. This could be a helpful tool in proper selection of
      patients for adjuvant chemotherapy.

PMID- 15570206
TI  - One hundred thirty-two consecutive pediatric liver transplants without hospital
      mortality: lessons learned and outlook for the future.
AB  - OBJECTIVE: Orthotopic liver transplantation (OLT) has become an established
      procedure for the treatment of pediatric patients with end-stage liver disease.
      Since starting our program in 1989, 422 pediatric OLTs have been performed using
      all techniques presently available. Analyzing our series, we have concluded that
      the year of transplantation is the most important prognostic factor in patient
      and graft survival in a multivariate analysis. METHODS: From April 2001 to
      December 1, 2003, 18 whole organs (14%), 17 reduced-size organs (13%), 53 split
      organs (42%; 46 ex situ, 7 in situ), and 44 organs from living donors (33%) were
      transplanted into 115 patients (62 male and 53 female). One hundred twelve were
      primary liver transplants, 18 were retransplants, one third and one fourth liver
      transplants. Of the 132 OLTs, 26 were highly urgent (19.7%). The outcome of these
      132 OLTs was retrospectively analyzed. RESULTS: Of 132 consecutive pediatric
      liver transplants, no patients died within the 6 months posttransplantation.
      Overall, 3 recipients (2%) died during further follow-up, 1 child because of
      severe pneumonia 13 months after transplantation and the second recipient with
      unknown cause 7 months postoperatively, both with good functioning grafts after
      uneventful transplantation. The third had a recurrence of an unknown liver
      disease 9 months after transplantation. The 3-month and actual graft survival
      rates are 92% and 86%, respectively. Sixteen children (12%) had to undergo
      retransplantation, the causes of which were chronic rejection (3.8%), primary
      nonfunction (3.8%), primary poor function (PPF; 1.5%), and arterial thrombosis
      (3%). The biliary complication rate was 6%; arterial complications occurred in
      8.3%; intestinal perforation was observed in 3%; and in 5%, postoperative
      bleeding required reoperation. The portal vein complication rate was 2%.
      CONCLUSIONS: Progress during the past 15 years has enabled us to perform
      pediatric liver transplantation with near perfect patient survival. Advances in
      posttransplant care of the recipients, technical refinements, standardization of
      surgery and monitoring, and adequate choice of the donor organ and
      transplantation technique enable these results, which mark a turning point at
      which immediate survival after transplantation will be considered the norm. The
      long-term treatment of the transplanted patient, with the aim of avoiding late
      graft loss and achieving optimal quality of life, will become the center of
      debate.

PMID- 15570207
TI  - Evolution of donor morbidity in living related liver transplantation: a single
      center analysis of 165 cases.
AB  - OBJECTIVE: During the last 14 years, living donor liver transplantation (LDLT)
      has evolved to an indispensable surgical strategy to minimize mortality of adult
      and pediatric patients awaiting transplantation. The crucial prerequisite to
      performing this procedure is a minimal morbidity and mortality risk to the
      healthy living donor. Little is known about the learning curve involved with this
      type of surgery. PATIENTS AND METHODS: From January 1991 to August 2003, a total
      of 165 LDLTs were performed in our center. Of these, 135 were donations of the
      left-lateral lobe (LL, segments II and III), 3 were of the left lobe (L, segments
      II-IV), 3 were full-left lobes (FL, segments I-IV), and 24 were of the full-right
      lobe (FR, segments V-VIII). We divided the procedures into 3 periods: period 1
      included the years 1991 to 1995 (LL, n = 49; L, n = 2; FR, n = 1), period 2
      covered 1996 to 2000 (LL, n = 47), and period 3 covered 2001 to August 2003 (LL,
      n = 39; FR, n = 23; FL, n = 3; L, n = 1). Perioperative mortality and morbidity
      were assessed using a standardized classification. Length of stay in intensive
      care unit, postoperative hospital stay, laboratory results (bilirubin, INR, and
      LFTs), morbidity, and the different types of grafts in the 3 different periods
      were compared. RESULTS: One early donor death was observed in period 1 (03/07/93,
      case 30; total mortality, 0.61.%). Since 1991, the perioperative morbidity has
      continually declined (53.8% vs. 23.4% vs. 9.2%). In period 1, 28 patients had 40
      complications. In period 2, 11 patients had 12 complications, and in period 3, 6
      patients had 9 complications. Within the first period, 1 donor underwent
      relaparotomy because of bile leakage. Postoperative hospital stay was 10 days, 7
      days, and 6 days, respectively. Donation of the full right lobe, in comparison
      with that of the left lateral lobe, resulted in a significantly diminished liver
      function (bilirubin and INR) during the first 5 days after donation but did not
      increase morbidity. One donor from period 1 experienced late death caused by
      amyotrophic lateral sclerosis. CONCLUSIONS: In a single center, morbidity after
      living liver donation strongly correlates to center experience. Despite the
      additional risks associated with temporary reduction of liver function, this
      experience enabled the team to bypass part of the learning curve when starting
      right lobe donation. Specific training of the surgical team and coaching by an
      experienced center should be implemented for centers offering this procedure to
      avoid the learning curve.

PMID- 15570208
TI  - Does the novel PET/CT imaging modality impact on the treatment of patients with
      metastatic colorectal cancer of the liver?
AB  - OBJECTIVE: To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2
      [18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer
      to the liver. BACKGROUND: Despite preoperative evaluation with ceCT, the tumor
      load in patients with metastatic colorectal cancer to the liver is often
      underestimated. Positron emission tomography (PET) has been used in combination
      with the ceCT to improve identification of intra- and extrahepatic tumors in
      these patients. We compared ceCT and a novel fused PET/CT technique in patients
      evaluated for liver resection for metastatic colorectal cancer. METHODS: Patients
      evaluated for resection of liver metastases from colorectal cancer were entered
      into a prospective database. Each patient received a ceCT and a PET/CT, and both
      examinations were evaluated independently by a radiologist/nuclear medicine
      physician without the knowledge of the results of other diagnostic techniques.
      The sensitivity and the specificity of both tests regarding the detection of
      intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the
      colorectal site were determined. The main end point of the study was to assess
      the impact of the PET/CT findings on the therapeutic strategy. RESULTS: Seventy
      six patients with a median age of 63 years were included in the study. ceCT and
      PET/CT provided comparable findings for the detection of intrahepatic metastases
      with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in
      establishing the diagnosis of intrahepatic recurrences in patients with prior
      hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the
      primary colo-rectal resection site were detected by ceCT and PET/CT with a
      sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was
      missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT
      failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%)
      (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic
      strategy in 21% of the patients. CONCLUSION: PET/CT and ceCT provide similar
      information regarding hepatic metastases of colorectal cancer, whereas PET/CT is
      superior to ceCT for the detection of recurrent intrahepatic tumors after
      hepatectomy, extrahepatic metastases, and local recurrence at the site of the
      initial colorectal surgery. We now routinely perform PET/CT on all patients being
      evaluated for liver resection for metastatic colorectal cancer.

PMID- 15570209
TI  - A two-stage hepatectomy procedure combined with portal vein embolization to
      achieve curative resection for initially unresectable multiple and bilobar
      colorectal liver metastases.
AB  - OBJECTIVE: To assess outcome after a 2-stage hepatectomy procedure (TSHP)
      combined with portal vein embolization (PVE) in the treatment of patients with
      unresectable multiple and bilobar colorectal liver metastases (MBCLM).
      BACKGROUND: Patients with MBCLM are often considered for palliative chemotherapy
      only, due to too small future remnant liver (FRL). Recently, right hepatectomy
      with simultaneous left liver wedge resections after previous right PVE has been
      reported in a curative intent. However, the growth of metastatic nodules in FRL
      after PVE can be more rapid than that of the nontumoral remnant hepatic
      parenchyma. Therefore, metastases located in the FRL should be ideally resected
      before PVE. Then, a right (or extended right) hepatectomy can be safely performed
      during a second-stage hepatectomy. Therefore, we analyzed our experience with the
      use of TSHP combined with PVE in treatment of MBCLM. PATIENTS AND METHODS:
      Between December 1996 and April 2003, 33 patients with unresectable MBCLM were
      selected for a TSHP. A right or an extended right hepatectomy was planned after
      treatment of left FRL metastases to achieve a curative resection. The first-stage
      hepatectomy consisted in a clearance of the left hemiliver by resection or
      radiofrequency destruction of metastases of the left FRL. Subsequently, a right
      PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the
      left hemiliver. Finally, a second-stage hepatectomy was planned to resect the
      right liver metastases. RESULTS: There was no operative mortality. Post-PVE
      morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and
      second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33
      patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%,
      respectively, in the 25 patients in whom the TSHP was completed. CONCLUSIONS: In
      selected patients with initially unresectable MBCLM, a TSHP combined with PVE can
      be achieved safely with long-term survival similar to that observed in patients
      with initially resectable liver metastases.

PMID- 15570210
TI  - Tumor progression while on chemotherapy: a contraindication to liver resection
      for multiple colorectal metastases?
AB  - OBJECTIVE: To evaluate the influence of the response to preoperative
      chemotherapy, especially tumor progression, on the outcome following resection of
      multiple colorectal liver metastases (CRM). SUMMARY BACKGROUND DATA: Hepatic
      resection is the only treatment that currently offers a chance of long-term
      survival, although it is associated with a poor outcome in patients with
      multinodular CRM. Because of its better efficacy, chemotherapy is increasingly
      proposed as neoadjuvant treatment in such patients to allow or to facilitate the
      radicality of resection. However, little is known of the efficacy of such a
      strategy and the influence of the response to chemotherapy on the outcome of
      hepatic resection. METHODS: We retrospectively analyzed the course of 131
      consecutive patients who underwent liver resection for multiple (> or =4) CRM
      after systemic chemotherapy between 1993 and 2000, representing 30% of all liver
      resections performed for CRM in our institution during that period. Chemotherapy
      included mainly 5-fluorouracil, leucovorin, and either oxaliplatin or irinotecan
      for a mean of 9.8 courses (median, 9 courses). Patients were divided into 3
      groups according to the type of response obtained to preoperative chemotherapy.
      All liver resections were performed with curative intent. We analyzed patient
      outcome in relation to response to preoperative chemotherapy. RESULTS: There were
      58 patients (44%) who underwent hepatectomy after an objective tumor response
      (group 1), 39 (30%) after tumor stabilization (group 2), and 34 (26%) after tumor
      progression (group 3). At the time of diagnosis, mean tumor size and number of
      metastases were similar in the 3 groups. No differences were observed regarding
      patient demographics, characteristics of the primary tumor, type of liver
      resection, and postoperative course. First line treatments were different between
      groups with a higher proportion of oxaliplatin- and/or irinotecan-based
      treatments in group 1 (P < 0.01). A higher number of lines of chemotherapy were
      used in group 2 (P = 0.002). Overall survival was 86%, 41%, and 28% at 1, 3, and
      5 years, respectively. Five-year survival was much lower in group 3 compared with
      groups 1 and 2 (8% vs. 37% and 30%, respectively at 5 years, P < 0.0001). Disease
      free survival was 3% compared with 21% and 20%, respectively (P = 0.02). In a
      multivariate analysis, tumor progression on chemotherapy (P < 0.0001), elevated
      preoperative serum CA 19-9 (P < 0.0001), number of resected metastases (P <
      0.001), and the number of lines of chemotherapy (P < 0.04), but not the type of
      first line treatment, were independently associated with decreased survival.
      CONCLUSIONS: Liver resection is able to offer long-term survival to patients with
      multiple colorectal metastases provided that the metastatic disease is controlled
      by chemotherapy prior to surgery. Tumor progression before surgery is associated
      with a poor outcome, even after potentially curative hepatectomy. Tumor control
      before surgery is crucial to offer a chance of prolonged remission in patients
      with multiple metastases.

PMID- 15570211
TI  - Staphylococcal enterotoxin A-induced hepatotoxicity is predominantly mediated by
      Fas ligand (CD95L).
AB  - OBJECTIVE: To determine the role of tumor necrosis factor alpha (TNF-alpha) and
      Fas ligand (FasL, CD95L) in superantigen-induced and endotoxin-induced liver
      injury. SUMMARY BACKGROUND DATA: Gram-positive bacteria are increasingly common
      causes of sepsis and multiorgan failure, but the pathophysiologic mechanisms of
      superantigen-provoked hepatotoxicity remain elusive. METHODS: Intravital
      fluorescence microscopy was used to study the liver microcirculation in mice
      challenged with superantigen (staphylococcal enterotoxin A, SEA) or endotoxin
      (lipopolysaccharide, LPS) combined with D-galactosamine. RESULTS: Administration
      of 10 microg LPS and 50 microg SEA caused similar hepatocellular damage as
      determined by liver enzymes and apoptosis. Notably, TNF-alpha-deficient mice were
      completely protected against hepatic injury provoked by LPS, whereas no
      protection was observed in response to SEA. On the other hand, FasL-deficient
      mice were protected against liver injury induced by SEA, but no protection was
      found when challenged with LPS. LPS increased clear-cut leukocyte recruitment,
      whereas SEA had no significant effect on leukocyte responses in the liver
      microcirculation. Leukocyte responses to LPS were decreased by >56% in TNF-alpha
      gene-targeted animals. Moreover, antiadhesive therapy, ie, immunoneutralization
      of P-selectin, which is an effective inhibitor of leukocyte recruitment,
      protected against LPS-induced but not against SEA-induced hepatic damage.
      CONCLUSIONS: These novel findings demonstrate that the mechanisms of hepatic
      injury in endotoxin-induced and superantigen-induced sepsis are principally
      different. On one hand, SEA-provoked hepatotoxicity is mediated by FasL and is
      not associated with leukocyte recruitment. On the other hand, liver damage
      provoked by LPS is mediated by TNF-alpha and characterized by prominent leukocyte
      responses. These data may facilitate development of more specific therapies
      against sepsis of different origins.

PMID- 15570212
TI  - Evidence-based value of prophylactic drainage in gastrointestinal surgery: a
      systematic review and meta-analyses.
AB  - OBJECTIVE: To determine the evidence-based value of prophylactic drainage in
      gastrointestinal (GI) surgery. METHODS: An electronic search of the Medline
      database from 1966 to 2004 was performed to identify articles comparing
      prophylactic drainage with no drainage in GI surgery. The studies were reviewed
      and classified according to their quality of evidence using the grading system
      proposed by the Oxford Centre for Evidence-based Medicine. Seventeen randomized
      controlled trials (RCTs) were found for hepato-pancreatico-biliary surgery, none
      for upper GI tract, and 13 for lower GI tract surgery. If sufficient RCTs were
      identified, we performed a meta-analysis to characterize the drain effect using
      the random-effects model. RESULTS: There is evidence of level 1a that drains do
      not reduce complications after hepatic, colonic, or rectal resection with primary
      anastomosis and appendectomy for any stage of appendicitis. Drains were even
      harmful after hepatic resection in chronic liver disease and appendectomy. In the
      absence of RCTs, there is a consensus (evidence level 5) about the necessity of
      prophylactic drainage after esophageal resection and total gastrectomy due to the
      potential fatal outcome in case of anastomotic and gastric leakage. CONCLUSION:
      Many GI operations can be performed safely without prophylactic drainage. Drains
      should be omitted after hepatic, colonic, or rectal resection with primary
      anastomosis and appendectomy for any stage of appendicitis (recommendation grade
      A), whereas prophylactic drainage remains indicated after esophageal resection
      and total gastrectomy (recommendation grade D). For many other GI procedures,
      especially involving the upper GI tract, there is a further demand for well
      designed RCTs to clarify the value of prophylactic drainage.

PMID- 15570216
TI  - Targeted gene expression in the chicken eye by in ovo electroporation.
AB  - PURPOSE: The chicken embryo lens is a classical model system for developmental
      and cell biology studies. To understand the molecular mechanisms that underlie
      the morphological changes that occur during lens development, it is important to
      develop an effective gene transfer method that permits the analysis of gene
      functions in vivo. In ovo electroporation has been successfully used for
      introducing DNA into neural and mesenchymal tissues of chicken embryos. In this
      study, we explored the possibility of using this technique to manipulate gene
      expression in lens epithelial and fiber cells, as well as in other cells of the
      chicken eye. METHODS: Two DNA constructs were used in this study. pCAX contains a
      chicken beta-actin promoter fused to the CMV IE enhancer to drive enhanced green
      fluorescent protein (EGFP) expression. pMES-cNf2 uses the same chimeric promoter
      to drive the expression of the chicken neurofibromatosis 2 (cNf2) and EGFP
      proteins in the same cell. Plasmid DNA was injected into the lumen of the lens
      vesicle in chicken embryos at stage 15. For corneal epithelial and retinal cell
      electroporation, DNA was placed near the surface ectoderm in the eye region or
      injected into the vitreous cavity, respectively. Electroporation was performed
      with one electrode above the eye and the other underneath the head of the embryo.
      Chicken embryos were harvested at different time points for EGFP expression
      analysis by immunohistochemistry. 5-bromo-2'-deoxyuridine (BrdU) incorporation
      assays were used to evaluate the effects of cNf2 on lens epithelial cell
      proliferation. RESULTS: A strong EGFP signal can be detected in lens cells 4 h
      after electroporation. The transfected cells maintain high levels of EGFP
      expression for at least 5 days. Overexpressing cNf2 in lens epithelial cells
      significantly inhibits cell proliferation. Ectopic expression of EGFP in corneal
      epithelial and retinal cells was also achieved by in ovo electroporation.
      CONCLUSIONS: We have demonstrated that exogenous DNA can be effectively
      introduced into lens, corneal and retinal cells in the living embryo by in ovo
      electroporation. In comparison to viral infection and transgenic mouse
      approaches, in ovo electroporation offers an easier and quicker way to manipulate
      gene expression during embryonic development. This technique will be a useful
      tool for exploring the molecular mechanisms of lens and eye development.

PMID- 15570217
TI  - Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1
      with identification of a novel mutation.
AB  - PURPOSE: To map the locus for autosomal recessive retinitis pigmentosa in a large
      Pakistani family and to determine the causative mutation. METHODS: A large family
      with multiple individuals affected by autosomal recessive retinitis pigmentosa
      was ascertained in the Punjab province of Pakistan as part of an ongoing project
      between the CEMB, Lahore, Pakistan and the NEI to identify genetic causes of eye
      diseases. After initial analysis of previously identified autosomal recessive
      retinitis pigmentosa loci, a genome wide scan was performed using microsatellite
      markers at about 10 cM intervals. Two point lod scores were calculated and
      haplotypes were analyzed in order to define disease locus. Bidirectional
      dideoxynucleotide sequencing was used to screen for mutations in candidate genes.
      RESULTS: In the genome wide scan, autosomal recessive retinitis pigmentosa in
      this Pakistani family showed linkage to an 11.7 cM region of chromosome 4p12
      between D4S405 and D4S1592 with a maximum lod score of 2.90 with D4S405 at
      theta;=0.01 Sequence analysis of CNGA1 identified a 2 bp deletion in exon 8:
      c.626_627delTA resulting in a frameshift, p.Ser209fsX26 in the translated
      protein. This mutation results in deletion of the COOH terminal 482 of 690 total
      amino acids in CNGA1 and their replacement by 25 novel amino acids before a
      premature termination. The mutation is found in a homozygous state in all 7
      affected individuals and was heterozygous in all 15 unaffected family members
      examined. The mutant allele of CNGA1 itself shows linkage to the disease with
      maximum lod score of 4.43 at theta;=0. CONCLUSIONS: The autosomal recessive
      retinitis pigmentosa in this family is caused by a mutation in CNGA1 gene. To our
      knowledge, this is the first report in which both linkage analysis and
      identification of a mutation support CNGA1 as a cause for autosomal recessive
      retinitis pigmentosa.

PMID- 15570218
TI  - Clinical description and genome wide linkage study of Y-sutural cataract and
      myopia in a Chinese family.
AB  - PURPOSE: To describe the clinical characteristics of a Y-sutural cataract
      associated with myopia in a large Chinese family and to identify the causative
      gene and mutation. METHODS: An autosomal dominant Y-sutural cataract and myopia
      were identified in members of a large family of Han ethnicity living in southern
      China. Ophthalmological examinations were performed and a medical history was
      taken. Blood samples were collected for DNA isolation. A genome wide scan was
      performed using markers spaced at about 10 cM intervals for genotyping and two
      point linkage analysis. Candidate genes were sequenced. RESULTS: Bilateral lens
      opacities, the only sign of cataract in early childhood and the most prominent
      sign in all affected individuals, involved the entire anterior Y and posterior
      inverted Y sutures, showing a feather duster like appearance. The Y-sutural
      cataract in this family mapped to an 11.4 cM (13.5 Mb) region between D3S3606 and
      D3S1309 on chromosome 3q22 with a maximum lod score of 5.7 at theta=0 for
      D3S1292. Sequence analysis of the beaded filament structural protein 2 (BFSP2)
      gene identified a previously described c.697_699delGAA (E233del) mutation which
      was present in all individuals with Y-sutural cataract but not in unaffected
      individuals and controls. Myopia, observed in 10 out of 12 cataract patients and
      significantly higher than that in unaffected offspring and siblings (1 out of 8),
      was independently mapped to a 61.2 cM (59 Mb) region between D3S3606 and D3S1262
      on 3q21.3-q27.2 with maximum lod score of 3.79. CONCLUSIONS: This Y-sutural
      cataract is caused by an E233del mutation in BFSP2 which provides additional
      evidence supporting mutations in BFSP2 as a cause for cataract and demonstrates
      phenotypic variability in cataracts caused by BFSP2. The Y-sutural opacity in the
      lens might be the typical and earliest sign for cataract caused by the BFSP2
      mutation. In addition, these results demonstrate a myopia susceptibility locus in
      this region, which might also be associated with the mutation in BFSP2.

PMID- 15570219
TI  - Cell and tissue specific expression of human Kruppel-like transcription factors
      in human ocular surface.
AB  - PURPOSE: The ocular surface, composed of the conjunctiva and the cornea, is
      essential for vision. Its integrity depends on numerous molecular and cellular
      processes such as proliferation, differentiation, apoptosis, adhesion, and
      extracellular matrix homeostasis, whose deregulation can induce ophthalmological
      pathologies. The Kruppel-like transcription factors (KLFs) family is made up of
      15 C2H2 zinc-finger proteins involved in vertebrate development and able to
      control cell proliferation, growth, and differentiation. In order to better
      define their respective roles in the human ocular surface, we decided to
      determine their pattern of expression in ocular tissues. We then focused on the
      expression of KLF4 and some of its target genes to establish KLF4's biological
      activities in human ocular surface. METHODS: Firstly, total mRNA was extracted
      from human total cornea, conjunctiva, corneal epithelial cells (primary culture
      and established cell line), corneal keratocytes (primary culture), corneal
      endothelial cells (established cell line), and conjunctival epithelial cells
      (established cell line) and submitted to RT-PCR experiments in order to determine
      the expression patterns of the different KLFs. Secondly, KLF4 protein
      localization was visualized by immunofluorescence assays at tissue and cell
      levels. Finally, KLF4 target genes (endoglin, ornithine decarboxylase) mRNA
      expression levels were determined by semi-quantitative RT-PCR, after KLF4
      transient transfection in human corneal epithelium (HCE) cells. RESULTS: We
      detected the presence of twelve transcripts of KLFs in the cornea (KLF2, KLF3,
      KLF4, KLF5, KLF6, KLF7, KLF8, KLF10, KLF11, KLF12, KLF13, and KLF16) and eight in
      the conjunctiva (KLF2, KLF3, KLF4, KLF6, KLF7, KLF10, KLF11, and KLF12). Under
      our conditions, the transcripts encoding KLF1 and KLF9 were never detected.
      Specific expression patterns of each KLF were also determined for the major
      cellular components of the human cornea and conjunctiva. KLF4 immunolocalization
      assays indicated its presence in both the cytoplasmic and nuclear compartments of
      conjunctival and corneal cells. KLF4 transient overexpression in HCE cells down
      regulated both endoglin and ODC mRNA levels. CONCLUSIONS: For the first time, we
      established the presence of a KLF network in the human ocular surface and
      illustrated the conservation of KLF4's biological properties in a corneal derived
      epithelial cell line.

PMID- 15570220
TI  - Cytokeratin 12 in human ocular surface epithelia is the antigen reactive with a
      commercial anti-Galpha q antibody.
AB  - PURPOSE: In our initial attempt to identify differentiation markers for ocular
      surface epithelia, we observed a unique staining pattern by a commercial anti
      Galphaq antibody. We further isolate and characterize the protein reactive with
      this anti-Galphaq antibody in human ocular surface epithelia. METHODS: Human
      donor corneoscleral buttons were sectioned and stained with a battery of
      commercial antibodies against Galpha proteins. Western blot analysis of cell
      lysates of corneal epithelial cells and HEK 293 cells transfected with Galphaq
      cDNA was used to determine the identity of the protein reactive with the anti
      Galphaq antibody (E-17). Comparisons were made with another anti-Galphaq antibody
      (G4415) and an anti-cytokeratin 12C (J7) antibody. The isolated proteins reactive
      with E17 and J7 were then analyzed with two dimensional isoelectric focusing.
      Polypeptide sequences were identified using matrix assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) after in
      gel protein digestion. RESULTS: The E-17 anti-Galphaq antibody preferentially
      stained the entire corneal epithelia and the suprabasal layers of the limbus with
      complete absence of staining in the basal limbus and conjunctiva. Western blot
      analysis of corneal epithelial cells showed that E-17 antibody identified a
      protein with a molecular weight of 55 kDa. However, the antibody did not react
      with the purported antigen, Galphaq protein (42 kDa) produced by Galphaq cDNA.
      Another anti-Galphaq antibody (G4415) did not react with the 55 kDa protein but
      did react with the 42 kDa Galphaq protein. Further comparison of the E-17
      antibody with the J7 antibody revealed that both recognized the 55 kDa band in
      one and two dimensional analysis. MALDI-TOF MS analysis confirmed that the 55 kDa
      protein of interest was actually cytokeratin 12 (CK12), rather than Galphaq
      protein. CONCLUSIONS: The commercial E-17 anti-Galphaq antibody did not react
      with Galphaq protein, its purported antigen. Instead, it recognized a 55 kDa
      protein, which was characterized to be cytokeratin 12 by isoelectric focusing and
      peptide fingerprinting with mass spectrometry. Based on its reactivity with CK12,
      this commercial E-17 can be used as a differentiation marker to study ocular
      surface epithelia.

PMID- 15570221
TI  - Probing alpha-crystallin structure using chemical cross-linkers and mass
      spectrometry.
AB  - PURPOSE: Alternatives to X-ray crystallographic techniques are needed to probe
      the structure of the hetero-oligomeric lens protein alpha-crystallin. We utilized
      mass spectrometry for 3 dimensional analysis (MS3D) to study the quaternary
      structural characteristics of this important lens protein and molecular
      chaperone. METHODS: We have employed two types of chemical cross-linkers to probe
      key protein-protein and protein-solvent interactions of alpha-crystallin using
      MS3D. Native alpha-crystallin was exposed to 3,3'-dithiobis[sulfosuccinimidyl
      propionate] (DTSSP) and the common fixative, formaldehyde. The reaction products
      were denatured and enriched in cross-linked and modified species using size
      exclusion chromatography. Tryptic digests of these fractions were purified using
      reverse phase HPLC and analyzed by both electrospray and matrix assisted laser
      desorption mass spectrometry. Comprehensive spectra for each C18 fraction were
      screened for ions with mass unique to each chemical treatment and candidate
      sequences matching the experimental data were assigned using MS3D "Links" and
      "ASAP" software. Selected ions were sequenced by collision induced dissociation.
      RESULTS: Peptides including residues 164-175 of alphaB-crystallin and residues 1
      99 of alphaA-crystallin were modified by formaldehyde and partially hydrolyzed
      DTSSP. Peptides containing modified lysines 11, 78, and 99 of alphaA-crystallin
      were sequenced and the modified amino acids identified. In addition, ions
      corresponding to intramolecular and/or intermolecular cross-links were assigned a
      sequence based on two criteria. First, the mass values observed were unique to a
      single cross-linking experiment and were not present in a control where no cross
      linker was utilized. Second, two unique ions detected from different cross
      linking experiments were correlated in that the structures assigned to the masses
      were equivalent apart from the structure of the cross-linker. One such
      correlation was found involving lysine121, within the "highly conserved alpha
      crystallin domain" of alphaB-crystallin, cross-linked to either lysine11 or
      lysine99 of alphaA-crystallin. Another two independent correlations involving
      lysine72 of alphaB-crystallin were found that indicate cross-linking of two
      subunits of alphaB-crystallin through this same residue. CONCLUSIONS: Sequences
      of peptides modified by partially hydrolyzed DTSSP and formaldehyde provide
      experimental evidence for models of alpha-crystallin quaternary structure that
      suggest a similar tertiary fold for both alphaA-crystallin and alphaB-crystallin.
      Analogous to multiple phosphorylations along the N-terminus of alphaB-crystallin,
      our data indicate that the same region of alphaA-crystallin, up to and including
      lysine99 is also relatively accessible to modification despite its
      hydrophobicity. Mass correlation between experiments using different reagents
      suggests that cross-linking occurred between N-termini of adjacent subunits of
      alphaB-crystallin in the native complex in support of the amphiphilic, toroidal,
      or "open micelle" models. In addition, multiple cross-links involving lysine121
      of the so called "dimer interface" region within the "highly conserved alpha
      crystallin domain" indicate that this region is a site of inter-subunit contacts
      in the native context.

PMID- 15570222
TI  - Gay and lesbian issues in pediatric health care.

PMID- 15570224
TI  - Electromyographic activity in the immobilized shoulder girdle musculature during
      contralateral upper limb movements.
AB  - The purpose of this study was to quantify electromyographic (EMG) activity in the
      immobilized shoulder girdle musculature at rest and during a battery of
      contralateral upper limb activities. Six asymptomatic men, aged 22 to 33 years,
      volunteered to participate. Fine-wire (supraspinatus, infraspinatus) and surface
      (deltoids, trapezii, biceps, serratus anterior) electrodes recorded the mean peak
      normalized (percent maximal voluntary contraction [%MVC]) EMG activity from each
      immobilized muscle at rest and during slow, fast, and incrementally resisted
      contralateral upper limb motions (5, 15, and 25 lb). EMG activity in all muscles
      was low during quiet immobilized standing (<1.5% maximal voluntary contraction
      [MVC]). During slow contralateral upper limb motions, activity ranged from 0.7%
      to 51.6% MVC (highest in trapezii) and was less than 15% MVC in the
      supraspinatus, infraspinatus, and anterior deltoid. Bimanual jar opening
      increased biceps activity from 7.8% to 16.1% MVC. During fast contralateral upper
      limb motions, peak infraspinatus activity increased to 56.7% during a fast
      straightforward reach. Supraspinatus activity was relatively high during all
      resisted backward-pulling motions (25.2%-32.1% MVC), whereas resisted forward
      reaching produced relatively little activity in the anterior deltoid,
      supraspinatus, infraspinatus, or biceps. Several slow and fast motions produced
      high trapezius activity (>45% MVC) with low supraspinatus, biceps, and anterior
      deltoid activities (<10% MVC). Our findings suggest that (1) immobilized shoulder
      girdle muscle EMG activity during quiet standing is negligible in asymptomatic
      individuals; (2) contralateral upper limb motions at self-selected speeds are not
      likely to be harmful to healing tissues; (3) during early healing periods,
      patients with biceps-labral injury should minimize bimanual activities, those
      with supraspinatus injury should avoid backward-pulling motions, and those with
      infraspinatus injury should avoid fast straightforward reaches; and (4) cross
      body, straightforward, or downward reaches at either a slow or fast speed may be
      appropriately prescribed as rehabilitative exercises that can be initiated while
      the shoulder remains immobilized.

PMID- 15570225
TI  - Should acute anterior dislocations of the shoulder be immobilized in external
      rotation? A cadaveric study.
AB  - The high recurrence rate associated with anterior shoulder dislocations may
      reflect inadequate healing of a Bankart lesion when the arm is immobilized in
      internal rotation. The effect of external rotation (ER) of the humerus on the
      glenoid-labrum contact of Bankart lesions was examined in 10 human cadaveric
      shoulders. The contact force between the glenoid labrum and the glenoid was
      measured in 60 degrees of internal rotation, neutral rotation, and 45 degrees of
      ER in 10 human cadaveric shoulders. No detectable contact force was found with
      the arm in internal rotation. The contact force increased as the arm passed
      through neutral rotation and reached a maximum at 45 degrees of ER. The contact
      force returned to 0 g when the arm was returned to neutral rotation. The mean
      contact force at 45 degrees of ER was 83.5 g. External rotation significantly
      increases the labrum-glenoid contact force and may influence the healing of a
      Bankart lesion.

PMID- 15570226
TI  - The impact of rotator cuff pathology on isometric and isokinetic strength,
      function, and quality of life.
AB  - The purposes of this study were to determine the reliability of strength and self
      reporting measures, the relationship of different strength measures to function,
      and the impact of rotator cuff pathology on patients' quality of life. Patients
      with nonoperated rotator cuff pathology (n = 36) and unaffected control subjects
      (n = 48) were assessed by use of the LIDO dynamometer to determine isometric and
      isokinetic (concentric and eccentric) strength of the shoulder rotators. The
      Shoulder Pain and Disability Index and Short Form-36 were self-reported by
      patients. Intraclass correlation coefficients (ICCs) were used to assess
      reliability, and Pearson correlations and multiple linear regression were used to
      determine the relationship between strength and function. The findings of this
      study include the following: (1) measures of self-reported physical disability
      had high reliability (ICC = 0.89); (2) the LIDO dynamometer reliably measured
      internal and external shoulder rotation strength in both concentric and isometric
      modes of testing (ICC = 0.78-0.94), whereas eccentric muscle actions had lower
      reliability; (3) all shoulder rotation strength measures were predictive of
      disability, with isometric external rotation strength being the most predictive
      (r = 0.56); and (4) the presence of rotator cuff pathology was highly predictive
      of impaired physical health quality of life (R(2) = 0.71, P < .001).

PMID- 15570227
TI  - Conversion of painful hemiarthroplasty to total shoulder arthroplasty: long-term
      results.
AB  - The purpose of this study was to evaluate the outcome after conversion of painful
      hemiarthroplasty to total shoulder arthroplasty (TSA). Sixteen consecutive
      patients who underwent revision TSA for failed humeral head replacement (HHR) at
      our institution from 1988 to 2000 were evaluated. The mean interval from the time
      of HHR to revision TSA was 3.5 years (range, 11 months to 10.5 years). At a mean
      5.5-year follow-up (range, 2-14 months), the results were excellent in 3 of 15
      (20%), satisfactory in 5 of 15 (33%), and unsatisfactory in 7 of 15 (47%). The
      mean American Shoulder and Elbow Surgeons score was 73.6 (range, 46.7-95) out of
      a possible 100. The mean visual analog pain score was 2.4 (range, 0-6) out of 10.
      Evidence of posterior glenoid erosion was found in 64% (7/11) of these patients.
      On the basis of the complexity of the surgery and the 47% unsatisfactory rate, we
      conclude that revision of a failed HHR to a TSA is a salvage procedure whose
      results are inferior to those of primary TSA.

PMID- 15570228
TI  - Minimum fifteen-year follow-up of Neer hemiarthroplasty and total shoulder
      arthroplasty in patients aged fifty years or younger.
AB  - Seventy-eight Neer hemiarthroplasties and thirty-six Neer total shoulder
      arthroplasties were performed in patients aged 50 years or younger between
      January 1, 1976, and December 31, 1985. Sixty-two hemiarthroplasties and twenty
      nine total shoulder arthroplasties with complete preoperative evaluation,
      operative records, and a minimum 15-year follow-up (mean, 16.8 years) or follow
      up until revision were included in the clinical analysis. Sixteen patients died,
      and seven were lost to follow-up. All 114 shoulders were included in the survival
      analysis. There was significant long-term pain relief (P < .01) and improvement
      in active abduction (P < .01) and external rotation (P < .01) with both
      procedures. There was not a significant difference between total shoulder
      arthroplasty and hemiarthroplasty with regard to pain relief, abduction, or
      external rotation. Radiographs were available for 53 hemiarthroplasties and 25
      total shoulder arthroplasties with a minimum 10-year follow-up. Humeral
      periprosthetic lucency was present more frequently after total shoulder
      arthroplasty (60%) compared with hemiarthroplasty (34%) (P = .0079). Glenoid
      erosion was present in 38 of 53 hemiarthroplasties (72%). Glenoid periprosthetic
      lucency was present in 19 of 25 total shoulder arthroplasties (76%). The results
      were graded by use of a modified Neer result rating system. Among the
      hemiarthroplasties, there were 6 excellent (10%), 19 satisfactory (30%), and 37
      unsatisfactory results (60%). Among total shoulder arthroplasties, there were 6
      excellent (21%), 9 satisfactory (31%), and 14 unsatisfactory results (48%). The
      estimated survival rate for hemiarthroplasty was 82% (95% CI, 74%-92%) at 10
      years and 75% (95% CI, 64%-86%) at 20 years. The estimated survival rate for
      total shoulder arthroplasty was 97% (95% CI, 91%-100%) at 10 years and 84% (95%
      CI, 68%-98%) at 20 years. The data from this study indicate that there is marked
      long-term pain relief and improvement in motion with shoulder arthroplasty.
      However, there is a moderate rate of hemiarthroplasty revision for painful
      glenoid arthritis. Unsatisfactory result ratings were most commonly a result of
      motion restriction from soft-tissue abnormalities. Great care must be exercised,
      and alternative methods of treatment considered, before either hemiarthroplasty
      or total shoulder arthroplasty is offered to patients aged 50 years or younger.

PMID- 15570229
TI  - The effect of limb support on muscle activation during shoulder exercises.
AB  - The purpose of this study was to determine the difference in demands on
      glenohumeral musculature during unsupported and supported active range-of-motion
      (AROM) shoulder exercises. Twenty healthy subjects volunteered for this study.
      Surface or fine-wire bipolar electrodes were applied to the infraspinatus,
      posterior deltoid, anterior deltoid, pectoralis major, and supraspinatus muscles.
      Subjects performed vertical wall slides and diagonal wall slides (45 degrees
      angle) with their hand in contact with the wall (supported) and not in contact
      with the wall (unsupported). Significantly greater supraspinatus activity was
      found in the unsupported exercises versus the supported exercises (F(4,76) =
      4.38, P = .003). Exercises performed in the 45 degrees diagonal position were
      more demanding on shoulder musculature than vertical exercises (F(1,19) = 19.3, P
      < .001). Although our results were obtained in healthy subjects and the
      implications in a pathological population are not clear, we suggest that when
      designing a progression of exercises for increasing shoulder muscular activity,
      supported short lever arm AROM exercises should precede unsupported long lever
      arm AROM exercises.

PMID- 15570230
TI  - Combined pectoralis major and latissimus dorsi tendon transfer for massive
      rotator cuff deficiency.
AB  - This report is a retrospective review of 11 consecutive patients treated with a
      combined transfer of the latissimus dorsi and pectoralis major tendons for
      massive rotator cuff deficiency. Each patient's chief complaint was diminished
      shoulder function and motion with little or no accompanying pain. The primary
      operative objective was to increase active shoulder motion. All 11 patients were
      followed up for at least 2 years (range, 24 to 42 months). The mean active
      elevation improved from 42 degrees preoperatively to 86 degrees postoperatively.
      The mean active external rotation improved from 0 degrees to 13 degrees. On the
      basis of the Medical Research Council scale, the mean abduction strength improved
      from 2.3 to 3.1 and the mean external rotation strength improved from 2.1 to 2.7.
      Overall, 4 patients made no improvement, 2 improved slightly, and 5 improved
      significantly. We conclude that a combined transfer of the latissimus dorsi and
      pectoralis major is a reasonable and safe procedure that may restore active
      elevation and external rotation in some patients' shoulders with a massive
      rotator cuff deficiency that have not responded favorably to traditional
      nonoperative and operative techniques. However, it is difficult to conclude,
      based on our experience, for which patients this surgery can be predictably
      successful.

PMID- 15570231
TI  - Continuous subacromial bupivacaine infusion for postoperative analgesia after
      open acromioplasty and rotator cuff repair: preliminary results.
AB  - Shoulder surgery is often associated with severe postoperative pain. Previous
      results in which single or continuous subacromial infiltration of local
      anesthetics was used as a method of postoperative pain relief have been
      contradictory. This study was initiated to evaluate the postoperative analgesic
      effect of a subacromial continuous 0.25% bupivacaine infusion at a rate of 6 mL/h
      after elective open shoulder surgery. We hypothesized that this procedure would
      improve postoperative analgesia while reducing morphine requirements. By use of a
      prospective, double-blind, randomized study design, 50 consecutive patients
      undergoing acromioplasty and rotator cuff repair surgery received a multiorifice
      catheter placed in the subacromial space. Twenty patients received 0.25%
      bupivacaine (group 1), and twenty-two patients received saline solution (group
      2). The primary endpoints in the two groups were total morphine consumption
      administered by patient-controlled analgesia and the patient's subjective pain
      level evaluated by a visual analog scale during the first 48 postoperative hours.
      No major technical or pharmacologic side effects were noticed, and the indwelling
      pain catheter was well tolerated by all patients. There was no statistically
      significant difference (P < .05) either in total cumulative morphine consumption
      microg/48 h (73.2 +/- 43.1 vs 60.9 +/- 35.9) or in subjective pain perception 10
      point visual analog scale (3.2 +/- 1.4 vs 3.1 +/- 1.5) between the two study
      groups. The continuous subacromial infiltration of 0.25% bupivacaine at a rate of
      6 mL/h is concluded to be ineffective in providing pain relief supplementary to
      patient-controlled analgesia after open rotator cuff repair and acromioplasty
      surgery.

PMID- 15570232
TI  - Positron emission tomography imaging of musculoskeletal tumors in the shoulder
      girdle.
AB  - The shoulder girdle presents unique features for the preoperative planning of
      musculoskeletal tumors. This is the first trial to evaluate positron emission
      tomography (PET) analysis for preoperative planning in shoulder girdle tumors.
      Fifty-two patients were examined with fluorine 18 fluoro-2-deoxy-D-glucose (FDG)
      PET and/or alpha-methyltyrosine (FMT)-PET. Imaging findings were visually
      inspected in conjunction with computed tomography and/or magnetic resonance
      imaging, and standardized uptake values (SUVs) were generated. FDG-PET may be
      useful for the detection of malignant tumors and screening for metastatic spread,
      with the qualitative assessment of heterogeneous biologic activity providing a
      correct approach for biopsy. The mean SUVs for malignant tumors were
      significantly higher than those for benign lesions. However, a useful cutoff SUV
      was not found in either FDG- or FMT-PET for differentiating malignant from benign
      tumors from receiver operating characteristic curve analysis. SUVs on FDG- and
      FMT-PET may merely be limited to differentiating malignant from benign tumors in
      the shoulder girdle.

PMID- 15570233
TI  - Repair of chronic distal biceps tendon ruptures using autologous hamstring graft
      and the Endobutton.
AB  - The purpose of this study was to report the results of anatomic repair for
      chronic distal biceps tendon ruptures by use of a semitendinosus autograft with
      the Endobutton. All 9 patients were satisfied with their outcome (mean, 8.0 on a
      visual analog scale ranging from 1-10) and were able to return to their jobs. The
      mean pain score was 0.5, and the postoperative flexion arc was from 3 degrees to
      147 degrees, with supination to 75 degrees and pronation to 62 degrees. The mean
      Mayo Clinic Elbow Score was 96.3 (range, 85-100). Cybex testing was carried out
      on 1 patient, demonstrating a marked improvement in supination strength. This
      technique yields good results with a high degree of patient satisfaction and no
      complications. An advantage of the technique is the concept of prefabrication,
      allowing the graft to be sutured to the biceps outside the wound and locked onto
      the radial tuberosity with the Endobutton.

PMID- 15570234
TI  - Arthroscopic synovectomy for the rheumatoid elbow: a short-term outcome.
AB  - We evaluated the results of arthroscopic synovectomy of 11 rheumatoid elbows in
      10 patients. All patients had severe pain and swelling, resulting from chronic
      synovitis, that had not responded to conservative treatment. We divided the
      patients into two groups according to preoperative Larsen grade: group A, grade
      1, 2, or 3 (n = 6); and group B, grade 4 (n = 5). The visual analog scale and the
      Elbow Evaluation Sheet of the Japanese Orthopaedic Association were used for
      preoperative and postoperative evaluation of pain and function. Arthroscopy was
      performed by use of the procedure of Poehling et al, without resection of the
      radial head. The mean follow-up period was 37 months. Visual analog scale and
      Japanese Orthopaedic Association scores improved significantly in both groups,
      with relief of pain and satisfactory functional results. We recommend this
      procedure for patients with a persistently painful, swollen elbow with Larsen
      grade 1 to 4 due to rheumatoid arthritis.

PMID- 15570235
TI  - Endoprosthetic elbow replacement in patients with solitary metastasis resulting
      from renal cell carcinoma.
AB  - Renal cell carcinoma is one of the most common cancers, and solitary metastasis
      to bone occurs in 2.5% of these patients. Localization of solitary metastasis to
      the elbow joint is rarer still, and data about these patients are limited.
      Because, in these cases, metastasis presents with osteolytic bone destruction,
      radical removal of solitary lesions should be considered. The aim of this
      treatment is to control the tumor locally, to reduce pain, and to restore
      function. We describe 4 patients with a solitary metastasis to the elbow from
      renal cell carcinoma who had the tumor resected and were then fitted with a
      custom-made elbow prosthesis. After surgical reconstruction, all patients
      reported markedly reduced pain and had a good functional outcome. The literature
      and our experience indicate that the prognosis for patients with just a solitary
      metastasis is sufficiently encouraging to warrant the use of all surgical and
      oncologic treatment options, especially if the interval between the diagnosis of
      the primary tumor and the development of the metastasis is lengthy.

PMID- 15570236
TI  - Passive tension and gap formation of rotator cuff repairs.
AB  - The objectives of this study were to quantify the relationship between passive
      tension of rotator cuff repairs and arm position and to examine the effect of
      this tension on repair gap formation. Five patients undergoing open surgical
      rotator cuff repair of the supraspinatus tendon were recruited. Tendon tension
      was recorded as the supraspinatus was advanced into a bone trough and secured.
      The relationship between arm position and repair tension was then measured.
      Standardized rotator cuff tears were created in 3 cadaveric shoulders and
      repaired by use of the intraoperative technique. The difference in tension
      measured between 0 degrees and 30 degrees abduction was statically applied for 24
      hours and the gap formation measured. Repair tension increased with advancement
      of the supraspinatus tendon into the bone trough. Abduction reduced the repair
      load. The mean reduction in load by 30 degrees abduction was 34 N. Twenty-four
      hours of 34-N loading caused gap formation of 9 mm in cadaveric rotator cuff
      repairs. Passive tension in surgically repaired rotator cuffs may contribute to
      repair failure and can be modified by arm positioning.

PMID- 15570237
TI  - The effects of glenoid component alignment variations on cement mantle stresses
      in total shoulder arthroplasty.
AB  - Loosening of the glenoid component has been cited as the most frequent cause of
      patient dissatisfaction with total shoulder arthroplasty, and it has been
      demonstrated in clinical studies that misalignment of the prostheses can be a
      causative factor. Finite element analyses of five different glenoid component
      alignments (central, anteverted, retroverted, inferiorly inclined, and superiorly
      inclined) were conducted in order to predict changes in the survivability of the
      cement mantle surrounding the glenoid component. The potential for mechanical
      failure of the mantle in the centrally aligned implant, during unloaded
      abduction, was seen to be lower than for any other alignment. Normal bone
      outperformed simulated rheumatoid models in all cases. Retroversion was worse
      than anteversion, and superoinferior misalignment was worse than anteroposterior.
      The quality of the supporting bone stock was found to be particularly significant
      to cement survivability, more so than the occurrence of eccentric loading of the
      joint. Shear forces acting on the glenoid component were found to be more
      detrimental than axial forces, resulting in a greater likelihood of failure
      toward the extremes of motion. The study suggests that significant efforts should
      be made to align the glenoid component correctly and also to ensure suitably
      consistent support of the prosthesis within the bone.

PMID- 15570238
TI  - Upper-third arm and shoulder reconstruction with the island latissimus dorsi
      flap.

PMID- 15570239
TI  - Massive nonspecific olecranon bursitis with multiple rice bodies.

PMID- 15570240
TI  - Ethical issues in the collection, storage, and research use of human biological
      materials.
AB  - Human biological materials (HBMs) are samples of blood, DNA, organs and tissues
      commonly obtained during routine surgical procedures or through direct donation
      by an individual. This article reviews four of the most pressing issues arising
      from the collection, storage, and use of HBMs in research: current regulations
      governing research with human subjects, misuse of genetic information, economic
      factors, and public knowledge.

PMID- 15570241
TI  - The effects of age and hyperhomocysteinemia on the redox forms of plasma thiols.
AB  - We assayed the redox forms of cysteine (reduced [CSH], oxidized [CSSC], and bound
      to protein [CS-SP]), cysteinylglycine (CGSH; cysteinylgycine disulfide [CGSSGC]
      and cysteinylglycine-protein mixed disulfide [CGS-SP]), glutathione (GSH;
      glutathione disulfide [GSSG] and glutathione-protein mixed disulfide [GS-SP]),
      homocysteine (Hcy; homocystine [HcyS] and homocystine-protein mixed disulfides
      [bHcy]), and protein sulfhydryls in the plasma of healthy subjects (divided into
      8 groups ranging in age from birth to 70 years) and patients with mild
      hyperhomocysteinemia associated with cardiovascular disease (heart-transplant
      patients) or vascular atherosclerosis, with or without renal failure. In healthy
      individuals, levels of disulfides and protein-mixed disulfides were more abundant
      than those of thiols, and those of protein-thiol mixed disulfides were higher
      than disulfides. Concentrations of CSH, GSH, and CGSH in the various groups had
      profiles characterized by a maximum over time. The concentration of Hcy was
      unchanged up to the age of 30 years, after which it increased. CSSC concentration
      increased gradually with age, whereas concentrations of the other disulfides were
      essentially unchanged. By contrast, the concentrations of all protein-thiol mixed
      disulfides, especially those with CSH, increased gradually with age. Ranks of
      distribution of the reduced forms changed with age (at birth, CSH > CGSH > GSH >
      Hcy; in 1- to 2-year-olds, CSH > GSH > CGSH > Hcy; and in 51- to 70-year-olds,
      CSH > CGSH = GSH > Hcy), whereas those of disulfides and protein-thiol mixed
      disulfides were substantially unchanged (in all age groups, CSSC > CGSSGC > GSSG
      = HcyS and CS-SP > CGS-SP > bHcy > GS-SP). In patients with pathologic
      conditions, plasma levels of disulfide forms CSSC, HcyS, CS-SP, and bHcy were
      significantly increased, whereas other redox forms of thiols were unchanged or
      showed variations opposite (increasing or decreasing) to control values. Maximal
      increases in disulfides and protein-thiol mixed disulfides were associated with
      renal failure. Our data suggest that increases in plasma bHcy concentrations in
      subjects with pathologic conditions were more likely the result of activation of
      thiol-disulfide exchange reactions between free reduced Hcy and CS-SP than of a
      direct action of reactive oxygen species.

PMID- 15570242
TI  - Intravascular release and urinary excretion of tissue factor pathway inhibitor
      during heparin treatment.
AB  - Tissue-factor-pathway inhibitor is the principal regulator of tissue factor
      induced coagulation. Heparin treatment mobilizes TFPI into the circulation and
      contributes to the anticoagulant effects of heparins. Previous studies have
      demonstrated a selective depletion of intravascular TFPI by unfractionated
      heparin (UFH) but not by low-molecular-weight heparin (LMWH). In this study we
      sought to investigate the time- and dose-dependent relationships between release
      of TFPI and lipoprotein lipase (LPL) in respons to UFH and LMWH and to
      investigate whether the selective depletion of TFPI by UFH but not by LMWH is
      related to differential urinary excretion of TFPI. Eight healthy males
      participated in an open crossover study in which participants were assigned to
      receive (1) continuous infusion of unfractionated heparin (UFH, 450 IU/kg/24 hr);
      (2) subcutaneous dalteparin, 100 IU/kg given twice at a 12-hr interval; (3)
      subcutaneous dalteparin, 200 IU/kg given once; or (4) saline-solution infusion.
      Similar dose-dependent mobilization of TFPI and lipoprotein lipase (LPL), another
      glucosaminoglycan (GAG)-anchored protein of the endothelial membrane, was
      observed after both subcutaneous and intravenous administration of heparins.
      However, UFH induced a more efficient release of both TFPI and LPL into plasma
      than did LMWH at equivalent anti-Xa levels, indicating molecular-weight
      dependence of the release reactions. However, LPL reached peak levels faster and
      was more rapidly cleared from the circulation than was TFPI, regardless of the
      treatment modality. Only trace amounts of TFPI were detected in the urine in a
      native form (38 kD). UFH and LMWH treatment reduced renal clearance of TFPI
      compared with the control regimen. Our findings suggest that displacement of TFPI
      from the endothelial-surface GAG is the main mechanism for TFPI release during
      heparin treatment in vivo and that differential urinary excretion of TFPI is not
      the explanation for selective depletion of TFPI during UFH treatment.

PMID- 15570243
TI  - A new L1446P mutation is responsible for impaired von Willebrand factor
      synthesis, structure, and function.
AB  - We report on a new mutation (4337T-->C) in exon 28 of the von Willebrand factor
      (VWF) gene, resulting in a substitution of L with P at residue 1446 (L1446P) of
      pre-pro-VWF. The defect is transmitted as a dominant trait and induces a reduced
      VWF synthesis, an abnormal VWF multimer pattern and a deficient VWF-platelet
      glycoprotein Ib interaction. The proband had low plasma and platelet VWF antigen
      levels, a reduced VWF collagen-binding capacity, and a disproportionately low VWF
      ristocetin cofactor activity, associated with the absence of ristocetin-induced
      platelet aggregation. Multimer analysis showed that the smaller multimers were
      slightly low, whereas the larger ones were significantly reduced or absent, with
      a clear cutoff between the two patterns. Similar hemostatic findings were
      observed in the proband's sister and nephew. Desmopressin administration restored
      VWF levels to near normal, but this was not so for VWF ristocetin cofactor
      activity or ristocetin-induced platelet aggregation. VWF multimers improved after
      desmopressin, moreover, with the larger forms restored and the smaller ones still
      relatively more represented. Recombinant P1446 VWF synthesis was reduced at
      heterozygous level, and its multimer pattern was similar to that observed in
      plasma VWF. These findings confirm the role of L1446P mutation in determining the
      von Willebrand disease (VWD) phenotype observed in our patients. Given the lack
      of large and intermediate VWF multimers, and the fact that the VWF-platelet
      interaction defect appears to be partially independent of multimer pattern, the
      VWD associated with L1446P mutation may belong to the type 2A/2M VWD variant.

PMID- 15570244
TI  - Sickle cell adhesion depends on hemodynamics and endothelial activation.
AB  - Venular microvascular circulation in patients with sickle cell anemia exhibits
      reduced and episodic blood flow. Sickle erythrocyte adhesion to postcapillary
      venule endothelium is postulated to initiate and propagate episodes of
      vasoocclusive pain. Hemodynamics likely mediate the adherence of sickle cells to
      endothelium, controlling delivery of potentially adherent erythrocytes and
      removal of loosely adherent erythrocytes on the endothelium. This study found a
      high dependence on shear stress of sickle erythrocyte adhesion to vascular cell
      adhesion molecule-1 (VCAM-1) on endothelium stimulated by tumor necrosis factor
      alpha (TNF-alpha). Shear stress varied from 1.0 dyne/cm 2 (microvascular venular
      flow), in which VCAM-1 ligand interactions induced by TNF-alpha primarily
      controlled adherence, to 0.1 dyne/cm 2 (low flow), in which stimulation had
      little effect on adherence. At shear stresses analogous to in vivo velocities
      from laser Doppler ultrasound studies (0.8 and 0.6 dyne/cm 2 ), TNF-alpha
      promoted 1.9- and 2.7-fold increases in adhesion compared with unstimulated
      (baseline) adherence. These findings suggest a dynamic vasoocclusive process that
      depends on both receptor expression and shear stress. These results indicate
      that, in the microvasculature, slightly reduced inflow rate, increased receptor
      expression, or both may result in large increases in sickle erythrocyte adhesion.

PMID- 15570245
TI  - Intrinsic factor studies: II. The effect of gastric juice on the urinary
      excretion of radioactivity after the oral administration of radioactive vitamin
      B(12).

PMID- 15570250
TI  - Graft-versus-host disease: how to translate new insights into new therapeutic
      strategies.
AB  - Graft-versus-host disease occurs when transplanted donor-derived T lymphocytes
      recognize major or minor histocompatibility complex proteins and their associated
      peptides expressed by recipient antigen-presenting cells. A widely accepted
      paradigm for the pathophysiology of acute GVHD is based on the existence of 3
      sequential steps: (1) injury to the host environment (as would occur during
      conditioning regimens); (2) donor T-cell activation, proliferation, and
      differentiation; and (3) damage to the target tissue caused by either
      cytotoxicity or indirectly by inflammatory cytokines. In order to reduce the
      incidence of GVHD, recent studies have focused on methods of prophylaxis as well
      as novel treatments for established GVHD. We review each phase in the development
      of acute GVHD and discuss recently developed interventions aimed to prevent or
      treat GVHD by interfering with these pathways.

PMID- 15570251
TI  - Radiation dose determines the degree of myeloid engraftment after
      nonmyeloablative stem cell transplantation.
AB  - A multivariate analysis of 121 dogs conditioned with 200, 100, or 50 cGy of total
      body irradiation (TBI) followed by hematopoietic stem cell transplantation from
      matched littermates showed that TBI dose was the only factor examined that was
      statistically significantly associated with the percentage of donor myeloid
      engraftment in stable long-term chimeras ( P = .008). To understand the direct
      effects of low-dose irradiation on hematopoietic stem/progenitor cells,
      nonirradiated and irradiated human CD34 + cells were evaluated for competitive
      repopulating ability in nonobese diabetic/severe combined immunodeficiency beta2m
      -/- mice. As expected, the results showed a radiation dose-dependent loss of
      competitive repopulating ability. Flow cytometric analysis indicated that, within
      a viable cell gate, there was reduced expression of P-selectin glycoprotein
      ligand-1 and L selectin on irradiated compared with nonirradiated CD34 + cells;
      this suggests that irradiated stem/progenitor cells may be compromised in their
      ability to home to or interact with the marrow microenvironment. However, the
      CD34 + /P-selectin glycoprotein ligand-1 dim cells also showed activation of
      caspase-3, indicating that they were destined to die. These results suggest that
      the TBI dose determines the degree of myeloid engraftment by compromising the
      resident stem/progenitor cell compartment.

PMID- 15570252
TI  - Distinct phases in recovery of reconstituted innate cellular-mediated immunity
      after murine syngeneic bone marrow transplantation.
AB  - Defects in immune reconstitution after hematopoietic stem cell transplantation
      confer extreme infection risk on to the transplant recipient. Perturbations in
      adaptive immune reconstitution have been well characterized, yet defects in
      reconstituted innate cellular-mediated immunity remain largely unstudied.
      Recovery in innate effector cells was defined by using an established murine
      model of autologous bone marrow transplantation. Cytokine induction after cell
      culture and systemic stimulation with pathogen-associated molecular patterns was
      also measured for control, transplant-recipient, and irradiated-only animals.
      Early reconstitution (7 to 14 days) of donor-derived macrophages, dendritic
      cells, and polymorphonuclear cells was associated with recovery in interleukin
      (IL)-12p70 and IL-6 production. Later reconstitution (21 days) of natural killer
      cells was associated with interferon (IFN)-gamma recovery. Hence, splenocyte
      innate cellular-mediated immunity recovered to normal levels in cellularity and
      IL-12p70, IFN-gamma, and IFN-alpha production by 21 days after transplantation.
      In contrast, levels of systemic cytokine production from transplant-recipient and
      irradiated-only animals were preserved despite incomplete or absent hematopoietic
      reconstitution. These results suggest that innate immune responses to systemic
      inflammatory challenges are largely intact after autologous bone marrow
      transplantation, whereas local innate cellular-mediated immunity within
      reconstituting lymphoid organs may be impaired. The disparate effects of
      autologous hematopoietic stem cell transplantation on host immune function may
      translate to differences in susceptibility to local versus systemic infectious
      challenges.

PMID- 15570253
TI  - A randomized trial comparing the combination of granulocyte-macrophage colony
      stimulating factor plus granulocyte colony-stimulating factor versus granulocyte
      colony-stimulating factor for mobilization of dendritic cell subsets in
      hematopoietic progenitor cell products.
AB  - The ability of granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) administration to increase the
      content of blood leucocytes and hematopoietic progenitor cells (HPCs) is well
      established, yet the effect of these cytokines on immune function is less well
      described. Recent data indicate that plasmacytoid dendritic cells (DC2) may
      inhibit cellular immune response. We hypothesized that administration of the
      combination of G-CSF and GM-CSF after chemotherapy would reduce the type 2, or
      plasmacytoid, DC2 content of the autologous blood HPC grafts compared with
      treatment with G-CSF alone. To test this hypothesis, 35 patients with lymphoma
      and myeloma were randomized to receive either G-CSF or the combination of G-CSF
      plus GM-CSF after chemotherapy, and blood HPC grafts were collected by apheresis.
      Cytokine-related adverse events between the 2 groups were similar. More than 2 x
      10(6)CD34 + cells per kilogram were collected by apheresis in 14 of 18 subjects
      treated with G-CSF and in 16 of 17 subjects treated with GM-CSF plus G-CSF ( p =
      not significant). There were minor differences between the 2 groups with respect
      to the content of T cells and CD34 + cells in the apheresis products. However,
      grafts collected from recipients of the combination of GM-CSF plus G-CSF had
      significantly fewer DC2 cells and similar numbers of DC1 cells compared with
      recipients treated with G-CSF alone. A third cohort of patients received
      chemotherapy followed by the sequential administration of G-CSF and the addition
      of GM-CSF 6 days later. Grafts from these patients had a markedly reduced DC2
      content compared with those from patients treated either with G-CSF alone or with
      the concomitant administration of both cytokines. These data, and recent data
      that cross-presentation of antigen by DC2 cells may induce antigen-specific
      tolerance among T cells, suggest that GM-CSF during mobilization of blood HPC
      grafts may be a clinically applicable strategy to enhance innate and acquired
      immunity after autologous and allogeneic HPC transplantation.

PMID- 15570254
TI  - Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem
      cell transplantation protocol for hematologic malignancy high-risk patients.
AB  - To reduce the toxicity of traditional conditioning regimens for allogeneic stem
      cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning
      with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240
      mg/m 2 ), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI
      500) daily for 3 days. T cell-replete SCT was performed from HLA-identical
      sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of
      7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or
      +5). Twenty-six high-risk hematologic malignancy patients were entered onto this
      study. All 24 patients who survived longer than 8 days engrafted, although 1
      patient experienced late graft failure. Deaths occurred in 21 of 26 patients
      because of infection (n = 7), progression/recurrence of primary disease (n = 6),
      aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five
      of these patients are enjoying disease-free survival with a median survival of
      1193 days after allo-SCT. The conditioning regimen induced modulation of surface
      expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor
      necrosis factor-alpha (but not interleukin-6) serum levels. In conclusion, single
      agent chemotherapy conditioning with T10B9 produced durable engraftment and long
      term survival in some patients who would not have qualified for a traditional
      allo-SCT.

PMID- 15570255
TI  - Favorable effect on acute and chronic graft-versus-host disease with
      cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow
      transplantation from HLA-identical sibling donors for acquired aplastic anemia.
AB  - Between August 1989 and November 2003, 33 patients at our center with acquired
      aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical
      sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies
      (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years).
      Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had
      previously experienced treatment failure with antithymocyte globulin-based
      immunosuppressive therapy. Unmanipulated bone marrow was used as the source of
      stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis
      was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in
      addition to cyclosporine. The conditioning regimen was well tolerated without
      significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4;
      secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete
      autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second
      allograft, n = 1). The cumulative incidence of graft failure and grade II to IV
      acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed
      extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival
      was 81% (95% confidence interval, 68%-96%). No unexpected early or late
      infectious or noninfectious complications were observed. We conclude that the
      conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well
      tolerated and effective for acquired aplastic anemia with HLA-matched sibling
      donors. The favorable effect on the incidence and severity of GVHD is noteworthy
      in this study and warrants further investigation.

PMID- 15570256
TI  - Allogenic stem cell transplantation for nonmalignant disorders using matched
      unrelated donors.
AB  - We here report 25 patients with nonmalignant disorders, ie, severe aplastic
      anemia (SAA, n = 12) or inborn errors of metabolism (IEM, n = 13), who underwent
      allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated high
      resolution typed HLA-A, -B, and -DRbeta1 identical donors. One patient had an HLA
      B subtype-mismatched donor. Conditioning for SAA mainly consisted of
      cyclophosphamide and total body irradiation, and that for IEM consisted of
      busulfan and cyclophosphamide. All patients received antithymocyte globulin
      during conditioning. After HSCT, they were given cyclosporine combined with
      methotrexate for immunosuppression. Two patients rejected their grafts: 1 died of
      pneumonia, and the other was successfully regrafted. The cumulative incidence of
      acute graft-versus-host disease grades II to IV was 24%, whereas chronic graft
      versus-host disease occurred in 21%. The 5-year survival rates were 83% in the
      SAA group and 85% in those with IEM. We conclude that HSCT with HLA-A, -B, and 
      DRbeta1 genomically matched unrelated donors in combination with antithymocyte
      globulin in the conditioning regimen gives encouraging results in patients with
      SAA or IEM.

PMID- 15570257
TI  - Re: Imatinib mesylate administration in the first 100 days after stem cell
      transplantation.

PMID- 15570264
TI  - Life-style modification in peripheral arterial disease.
AB  - OBJECTIVE: To review the published evidence supporting the use of life-style
      modification in peripheral arterial disease (PAD). DESIGN: A systematic search of
      the medical literature was performed for relevant studies. MATERIALS: The
      publications obtained were then searched for randomised clinical trials which
      reported end-points of mortality or major cardiovascular event rates with various
      life-style modifications. RESULTS: Only one randomised controlled trial was found
      reporting relevant end-points. Other trials were of other end-points such as
      walking distance or biochemical markers. CONCLUSIONS: There is a lack of
      randomised controlled data proving the benefit of life-style modification in
      improving mortality and reducing cardiovascular events in patients with PAD.
      Despite this there is sufficient evidence to recommend some life-style
      modification as part of the overall approach to risk reduction in these patients.
      There is compelling evidence to support smoking cessation, increased exercise and
      improved diet.

PMID- 15570265
TI  - Clinical significance of superficial vein thrombosis.
AB  - OBJECTIVE: To evaluate the clinical implications of superficial thrombophlebitis
      (STP) including its demographic characteristics, distribution, risk factors,
      relationship with deep vein thrombosis (DVT), pulmonary embolism (PE), diagnosis
      and management. METHODS: Data were collected from relevant papers using a MEDLINE
      search and an extensive bibliography review. Studies were considered only when
      they contained pertinent material to STP. Thirty-seven papers were analysed.
      RESULTS: The diversity of patients and methods used in the different studies made
      the comparison among them difficult. STP is a common condition with an
      underestimated prevalence. There are many risk factors associated with STP but
      the strongest relation was seen with hypercoagulable states. Malignancy may be
      another important factor but the strength of this association remains unknown.
      Coexistence with DVT was found in 6-53%. PE occurred in 0-33.3%. Propagation to
      DVT ranged from 2.6 to 15%. Treatment has not been standardised and may include
      elastic compression, anti-inflammatory drugs, anticoagulation and surgery.
      CONCLUSION: The limited number of prospective randomised studies on STP does not
      allow strong recommendations to be given. Although STP most often is perceived as
      benign, it can coexist with or progress to DVT, and even give rise to PE. It is
      also associated with hypercoagulability and malignancy.

PMID- 15570267
TI  - Total laparoscopic aortobifemoral bypass.
AB  - AIM: To assess the feasibility of aortobifemoral bypass by a laparoscopic
      approach. MATERIAL AND METHODS: During November 2002 through July 2003 a total of
      21 patients with aorto-iliac occlusive disease underwent total laparoscopic
      aortobifemoral bypass surgery. RESULTS: The median operative time was 240 (range
      150-420) min with a median aortic cross-clamp time of 60 (30-120) min. Operating
      time was reduced with experience. The median blood loss was 500 (100-2500) ml.
      One conversion to open surgery for acute dilation of the small bowel was
      necessary. Post-operative complications occurred in five patients (coagulation
      problems, disseminated intravascular coagulation secondary to thrombosis of the
      left limb, cerebro-vascular accident, dyspnoea, lymph leak) and there was no peri
      operative death. Median hospital stay was 7 (5-30) days. CONCLUSION: Aorto
      bifemoral bypass using a total laparoscopic approach can be performed safely. As
      all new techniques, a learning curve is observed. This new technique should be
      evaluated in a larger randomised trial to assess its clinical value in comparison
      to conventional surgery.

PMID- 15570268
TI  - Mid-term survival and costs of treatment of patients with descending thoracic
      aortic aneurysms; endovascular vs. open repair: a case-control study.
AB  - OBJECTIVES: To evaluate the results of open surgery or endovascular stent graft
      repair of descending thoracic aortic aneurysm (TAA). DESIGN, MATERIALS AND
      METHODS: This is a retrospective multicenter study of 95 patients undergoing TAA
      repair (42 stent grafts, 53 open repair). The median age was 67 years. Post
      operative complications, mid-term survival and costs were assessed. The results
      were pooled with data in the literature. RESULTS: After a mean follow up of 26
      months (open group) and 15 months (endovascular group) survival was similar for
      patients treated by either repair method. Post-operative pneumonia was more in
      the open group (p <0.02). The hospital costs of open treatment were 40% more than
      that of the endovascular procedure. Combining the present results with pooled
      data from the literature the peri-operative mortality and paraplegia rate was
      less in the endovascular group (p <0.05). CONCLUSIONS: These retrospective data
      suggest that endografting of descending thoracic aneurysms can be performed with
      less peri-operative morbidity, at lower hospital costs, but with equal mid-term
      life expectancy, compared with open grafting.

PMID- 15570269
TI  - Penetrating atherosclerotic ulcers of the infrarenal aorta: life-threatening
      lesions.
AB  - OBJECTIVES: To analyze the incidence, clinical features, natural history, and
      treatment of penetrating atherosclerotic ulcers (PAU) of the abdominal aorta.
      MATERIAL AND METHODS: From January 2000 to June 2003, an abdominal PAU was
      diagnosed at our institution in eight patients (seven men, one woman; mean age 70
      year). These eight cases were analyzed together with 38 additional cases found in
      a review of the literature (total 46 cases). RESULTS: Occurring at an incidence
      of approximately 1%, abdominal PAU are less common than thoracic PAU. Seventy
      percent of cases are symptomatic: pain 52.5% (n =21), acute lower limb ischemia
      due to distal embolism 12.5% (n =5), shock 5% (n =2). Diagnosis is usually made
      by CT (66%) (n =26) that demonstrates a PAU in 35% (n =16) of cases, a
      subadventitial pseudoaneurysm in 28% (n =13), and rupture in 37% (n =17). An
      intramural hematoma (IMH) is observed in 9% (n =4) of cases. There were no cases
      of aortic dissection in this series. Calcifications of the abdominal aorta were
      frequent (56%) (n =26); while intra-aortic mural thrombus was found in 24% of
      cases (n =11), and 46% of patients (n =21) had an associated aneurysm. Twelve
      patients were treated medically while 34 underwent surgery (one postoperative
      death). CONCLUSION: Review of the literature and this series suggests that PAU of
      the abdominal aorta is a life-threatening lesion, the main risk being rupture.
      Surgical management is recommended owing to its low morbidity and mortality.

PMID- 15570270
TI  - Surgical treatment of persistent type 2 endoleaks, with increase of the aneurysm
      sac: indications and technical notes.
AB  - OBJECTIVE: Unsolved type 2 endoleaks and aneurysmal sac increasing after
      endovascular aneurysm repair (EVAR) can be fixed with surgical sacotomy, ligation
      of the patent backbleeding vessels and preservation of the endograft. The aim of
      the paper is to highlight the technique as a feasible procedure in alternative to
      the removal of the graft. MATERIALS AND METHODS: Four male patients whose
      aneurysm sac maximum transverse diameter had increased by 5 mm or more, without
      evidence of endoleak, migration or structural alteration of the endografts. The
      surgical access was by medial laparotomy in one case, flank incision in two cases
      and mini-laparotomy with laparoscopic assistance in the fourth case. Patients
      were followed with spiral CT and duplex ultrasound at discharge and at 6-12
      months. RESULTS: All procedures were carried out, without complication. Two
      patients required intensive care unit (ICU) admission and the average post
      operative hospital stay was 10 days (range 6-13). All patients are currently
      alive with a functioning endograft, at an average follow-up of 14.7 months.
      CONCLUSIONS: Sacotomy, leaving the endograft in place, appears to be a feasible
      therapeutic option, less invasive than conversion to open repair. This technique
      merits further study.

PMID- 15570271
TI  - A novel approach: ascending venous arterialization for atherosclerosis
      obliterans.
AB  - OBJECTIVE: Lower limb arterial occlusion with no patent distal artery suitable
      for revascularisation is a common problem. The aim of this study was to assess
      the role of revascularisation to distal veins (ascending venous arterialization)
      in patients not reconstructable by conventional bypass. METHOD: Ascending venous
      arterialization is a distal arteriovenous fistula. Reversed great saphenous vein
      grafts, from above the knee, were anastomosed to the common femoral artery,
      superficial femoral artery or popliteal artery and distally to the saphenous vein
      at the level of medial malleolus. No intervention was done to destroy the venous
      valves. The great saphenous vein was ligated below the knee. In this way,
      oxygenated blood could reach to dorsal venous arch and the tissues below the knee
      in an ascending fashion through the great saphenous vein, which was not removed.
      RESULTS: All of the patients recovered immediately after the operation. The
      lesions on the feet and on the toes of the patients improved in a short time.
      Intermittent claudication of the patients disappeared. Strong pulses were
      detected on the dorsal venous arch with manual Doppler in 3 weeks. The below knee
      tissues were perfused with the applied technique. CONCLUSION: Ascending venous
      arterialization can be applied for limb salvage to the patients who do not have a
      suitable arterial bed to revascularize with conventional techniques.

PMID- 15570272
TI  - Cerebral haemodynamic disturbances in patients with moderate carotid artery
      stenosis.
AB  - OBJECTIVE: Dynamic MR perfusion imaging can detect cerebral perfusion deficits
      resulting from severe internal carotid artery (ICA) stenosis. It is unknown,
      however, whether moderate ICA stenosis (50-69%) also causes haemodynamic
      disturbance. We investigated whether cerebral perfusion deficits were detectable
      in patients with moderate ICA stenosis. METHODS: Eighteen patients underwent T2*
      weighted cerebral MR perfusion imaging with a gadolinium based contrast agent.
      Differences in mean time to peak (mTTP) and relative cerebral blood volume (rCBV)
      between cerebral hemispheres were calculated for middle cerebral artery territory
      regions by a reader blinded to the angiographic and clinical findings. RESULTS:
      There were significant differences in mTTP between cerebral hemispheres in 15
      patients with a mean inter-hemispheric delay in mTTP of 0.49 s (95% confidence
      intervals, 0.25 and 0.72 s) which was statistically significant ( p <0.001). In 1
      patient with bilateral moderate stenosis there was no difference in mTTP.
      CONCLUSIONS: Moderate ICA stenosis results in significant ipsilateral cerebral
      perfusion delays detectable by dynamic susceptibility MRI. Follow-up studies
      might reveal whether these delays improve following carotid endarterectomy.

PMID- 15570273
TI  - Surgical thrombectomy followed by intraoperative endovascular reconstruction for
      symptomatic ilio-femoral venous thrombosis.
AB  - OBJECTIVES: To evaluate the efficacy of surgical thrombectomy combined with
      endovascular reconstruction for acute ilio-femoral/caval venous thrombosis.
      METHODS: Twenty consecutive patients with acute, symptomatic ilio-femoral/-caval
      thrombosis underwent valve-preserving thrombectomy with immediate endovascular
      repair between October 1996 and October 2003. Thrombectomy was classified by
      intraoperative venography as: TYPE I=complete, TYPE II=partial, TYPE III=complete
      with stenosis other than thrombus, TYPE IV=permanent occlusion. TYPEs I and IV
      were excluded from this analysis because endovascular repair was not performed.
      RESULTS: Left-sided venous thrombosis predominated (90%). Lesions were located in
      the common iliac vein (85%), the external iliac vein (10%), and the inferior vena
      cava (5%). Three TYPE II lesions and 17 TYPE III lesions (11 spurs, one
      hypoplasia, one fibrosis, one haematoma, and three others) were diagnosed.
      Catheter-directed recanalisation (thrombectomy/thrombolysis) resolved TYPE II
      lesions in three patients. Balloon angioplasty (one patient), iliac stenting (15
      patients [two with thrombolysis]), and caval stenting (one patient) were employed
      in TYPE III stenoses. No serious complication or death occurred. Mean follow-up
      was 21 months. Of 20 patients clinical results were excellent in 18 patients who
      maintained patency of their reconstructed iliac veins. Primary and secondary
      patency rates were 80 and 90%, respectively. CONCLUSIONS: Ilio-caval venous
      obstructions detected intraoperatively can be reconstructed in a one-stage
      combined procedure. The specific endovascular approach depends on the type of
      residual venous obstruction. Excellent mid-term results indicate that the
      proposed thrombectomy classification (TYPE I-IV) and treatment algorithm
      optimises the results in selected patients with symptomatic venous thrombosis.

PMID- 15570274
TI  - Prospective randomised study of endovenous radiofrequency obliteration (closure)
      versus ligation and vein stripping (EVOLVeS): two-year follow-up.
AB  - PURPOSE: To study intermediate clinical outcomes, rates of recurrent varicosities
      and neovascularisation, ultrasound changes of the GSV, and the quality of life
      changes in patients from EVOLVeS trial. METHODS: Forty five patients were re
      examined 1 year and 65 two years after treatment. Follow-up visits included
      clinical examination with CEAP classification and calculation of venous clinical
      severity score (VCSS), ultrasound examination, and a quality of life
      questionnaire. RESULTS: The clinical course of the disease (CEAP, VCSS) was
      similar in the two treatment groups. 51% of the GSV trunks occluded by RFO
      underwent progressive shrinkage with the external diameter decreased from 6.3 SD
      1.4 mm at 72 h after treatment to 2.9 SD 1.5 mm at 2 years. An additional 41% of
      the GSV became undetectable by ultrasound at 2-year follow up. In two patients we
      observed re-opening of an initially closed GSV lumen. Neovascularisation was
      found in one RFO case and in four S and L cases. Cumulative rates of recurrent
      varicose veins at combined 1 and 2 years follow-up were 14% for RFO and 21% for S
      and L (NS). The difference in global QOL score in favour of RFO re-appeared at 1
      year and remained significant at 2 years after treatment. CONCLUSION: The 2-year
      clinical results of radiofrequency obliteration are at least equal to those after
      high ligation and stripping of the GSV. In the vast majority of RFO patients the
      GSV remained permanently closed, and underwent progressive shrinkage to eventual
      sonographic disappearance. Recurrence and neovascularisation rates were similar
      in the two groups although limited patient numbers prevent reliable statistical
      analysis. Improved quality of life scores persisted through the 2-year
      observations in the RFO group compared to the S and L group.

PMID- 15570275
TI  - Risk factors for delayed healing and recurrence of chronic venous leg ulcers--an
      analysis of 1324 legs.
AB  - OBJECTIVE: Despite similar disease patterns and treatment, there is great
      variation in clinical outcome between venous ulcer patients. The aim of this
      study was to identify independent risk factors for venous ulcer healing and
      recurrence. METHODS: Consecutive patients assessed by a specialist nurse-led leg
      ulcer service between January 1998 and July 2003 with an ABPI>0.85 were included
      in this study. Independent risk factors for healing and recurrence were
      identified from routinely assessed variables using a Cox regression proportional
      hazards model. RESULTS: A total of 1324 legs in 1186 patients were studied. The
      24-week healing rate was 76% and 1 year recurrence rate was 17% (Kaplan-Meier
      life table analysis). Patient age (p <0.001, HR per year 0.989, 95% CI 0.984
      0.995) and ulcer chronicity (p =0.019, HR per month 0.996, 95% CI 0.993-0.999)
      were independent risk factors for delayed ulcer healing. Ulcer healing time (p
      <0.001, HR per week 1.016, 95% CI 1.007-1.026) and superficial venous reflux not
      treated with surgery (p =0.015, HR 2.218, 95% CI 1.166-4.218) were independent
      risk factors for ulcer recurrence. CONCLUSIONS: Elderly patients with
      longstanding ulcers should be targeted for further research and may benefit from
      adjunctive treatments to improve clinical outcomes. Patients not treated with
      superficial venous surgery were at increased risk of leg ulcer recurrence.

PMID- 15570276
TI  - The influence of superficial venous surgery and compression on incompetent calf
      perforators in chronic venous leg ulceration.
AB  - OBJECTIVES: Previous studies have suggested that perforating vein incompetence is
      reduced by surgery to superficial veins. This study analysed the effect in a
      randomised clinical trial. DESIGN: Retrospective analysis of duplex data.
      METHODS: Patients in this study were part of the ESCHAR randomised controlled
      trial. All patients had chronic venous leg ulceration with superficial venous
      reflux. Patients were treated with compression bandaging alone or compression
      plus superficial venous surgery. Legs were assessed using colour venous duplex
      prior to treatment and at 3 and 12 months. RESULTS: Of 500 patients recruited to
      the ESCHAR trial, 261 were included in this study. One hundred and forty six of
      261 legs were treated with compression alone and 115/261 underwent compression
      and superficial venous surgery. In the compression group, more legs had
      incompetent perforators at 12 months (77/131) compared to baseline (61/146, p
      =0.010, Wilcoxon Signed Ranks test for paired data in 131 legs). Following
      surgery, significantly fewer legs had incompetent calf perforators (59/115 vs
      44/104 at 12 months, p =0.001, Wilcoxon Signed Ranks test for paired data in 104
      legs). In addition, significantly fewer legs in the compression and surgery group
      developed new perforator incompetence in comparison to the group treated with
      compression alone (12/104 vs 36/131, p =0.003, Chi-Squared test). CONCLUSION:
      Surgical correction of superficial reflux may abolish incompetence in some calf
      perforators and offer protection against developing new perforator incompetence.

PMID- 15570277
TI  - Sciatic nerve varices.
AB  - OBJECTIVE(S): To describe patients presenting with sciatic nerve varices (SNV),
      presenting pitfalls in diagnosis and management. DESIGN: Case series. METHODS:
      Patients were investigated using duplex ultrasonography pre-operatively in three
      cases. Treatment was undertaken both by surgery and by foam sclerotherapy.
      RESULTS: Clinically, SNV appeared just below the popliteal skin crease, lateral
      to the small saphenous vein (SSV). In two cases SNV occurred alone, in two
      further cases SNV occurred in conjunction with varices from other sources.
      Symptoms of 'sciatic' pain were present in all. Foam sclerotherapy (1%
      Polidocanol) was undertaken in one case with a varix. Complete obliteration of
      the vein and resolution of all symptoms was achieved at the 1-month follow-up
      examination. Surgical management was used in the other cases. CONCLUSION: The
      sciatic nerve vein follows the fibular saphenous nerve (lying superficial to the
      fascia in the leg). This nerve arises from the common peroneal nerve (in the
      popliteal fossa), and is a major branch of the sciatic nerve. Varices of the
      associated vein appear to be the result of a dysplasia. This condition may be
      more common than is currently recognised.

PMID- 15570278
TI  - The influence of asymptomatic significant carotid disease on mortality and
      morbidity in patients undergoing coronary artery bypass surgery.
AB  - OBJECTIVES: Controversy exists regarding the optimal management of patients with
      coexisting coronary and extracranial carotid artery disease. This study
      investigates the incidence of death, cerebrovascular events and myocardial
      infarction (MI) in patients with asymptomatic significant carotid artery disease
      undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective
      cohort. METHODS: Fifty patients with asymptomatic carotid stenoses > or =70%
      associated with cervical bruits undergoing CABG without prophylactic carotid
      endarterectomy (CEA) were followed up over a median period of 68 months following
      surgery cerebrovascular events, MI and mortality were recorded. All patients
      received optimal secondary prevention for cardiovascular disease unless
      contraindicated. RESULTS: No cerebrovascular events occurred within 30 days of
      surgery. One patient suffered an ipsilateral transient ischaemic attack (TIA) 14
      months after CABG. Two patients died within 30 days; one from an MI, the other
      from pancreatitis. Three deaths occurred after 30 days; one from MI, one from
      primary lung cancer and one following rupture of an abdominal aortic aneurysm. No
      non-fatal MIs occurred. CONCLUSIONS: In this patient group the overall risk of
      death, cerebrovascular events and MI was 4% during the first 30 days
      postoperatively and 8% thereafter. This compares favourably with published series
      for staged or combined CEA-CABG procedures. For asymptomatic significant carotid
      disease, prophylactic CEA prior to CABG does not appear to confer any advantage
      over CABG alone.

PMID- 15570279
TI  - Patch corrugation on duplex ultrasonography may be an early warning of prosthetic
      patch infection.
AB  - Four of 10 patients presenting with prosthetic patch infection after carotid
      endarterectomy (CEA) were noted to have Duplex evidence of 'corrugation' of the
      prosthetic patch, without false aneurysm formation. In three, corrugation
      preceded diagnosis of overt patch infection by up to 11 months. In the fourth
      patient, awareness of the potential significance of patch corrugation enabled
      timely treatment of an otherwise unrecognized patch infection. Even if other
      imaging modalities are normal, the presence of patch corrugation on Duplex should
      prompt the surgeon to (at least) consider the possibility of patch infection.

PMID- 15570280
TI  - Cystic adventitial disease: a trap for the unwary.
AB  - Cystic adventitial disease is an uncommon condition. A case of cystic adventitial
      disease of the popliteal artery is reported in a young man who has been followed
      up for 14 years after surgical treatment. Early recognition and treatment of the
      condition will prevent progression to popliteal thrombosis and critical
      ischaemia. However, diagnosis of the condition is difficult. Characteristic
      features in the presenting history, such as fluctuation in severity of symptoms,
      sudden onset after vigorous activity and delayed recovery time after cessation of
      exercise are identified, which should help the clinician avoid misdiagnosis and
      delayed diagnosis of the condition. The clinician is also warned of the
      associated misleading clinical features such as the presence of normal peripheral
      pulses and normal ankle pressures in some cases of CAD.

PMID- 15570281
TI  - Primary aorto-colic fistula arising from a post-traumatic aortic pseudoaneurysm.

PMID- 15570285
TI  - Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation
      (BMT) in chronic myeloid leukaemia: BMT prolongs survival.
AB  - INTRODUCTION: Whether busulphan-treated patients develop blastic transformation
      earlier than hydroxyurea treated has been a controversial issue. In a randomised
      prospective study, we examined the busulphan versus hydroxyurea influence on time
      to blast crisis and on survival. When we opened our study in 1984, the clinical
      benefit of allogeneic bone marrow transplantation (BMT) was not well known; to
      follow up the long-time outcome of this treatment was therefore of great
      interest. MATERIALS AND METHODS: Previously untreated CML patients were randomly
      started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The
      end points of the study were overall survival and time to blast crisis. A total
      of 26 patients subsequently underwent BMT. RESULTS: A total of 179 patients were
      randomised, 90 of hydroxyurea, and 89 to busulphan treatment. There was no
      significant difference in survival between hydroxyurea- and busulphan-treated
      patients (P = 0.46); median survival was 3.5 and 3.2 years, respectively. In all,
      85 of the patients were subsequently diagnosed with blast crisis, 41 in the
      busulphan and 44 in the hydroxyurea group. There was no significant difference
      between the two groups (P = 0.91). The 26 patients who were allotransplanted
      survived significantly longer than those who were not transplanted (P = 0.0001).
      The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46
      and 2%, respectively. The median survival was 4.7 years for the transplanted and
      3.3 years for the nontransplanted patients. CONCLUSION: We did not find any
      difference between hydroxyurea and busulphan treatment, either in overall
      survival or in blast crisis-free survival; transplanted patients survived
      significantly longer than nontransplanted patients.

PMID- 15570286
TI  - Second treatment with rituximab in B-cell non-Hodgkin's lymphoma: efficacy and
      toxicity on 41 patients treated at CHU-Lyon Sud.
AB  - The purpose of this study was to evaluate retrospectively the effect of a second
      treatment with rituximab for patients who progressed after a response to a first
      treatment. We analysed the charts of 41 patients treated at CHU Lyon-Sud between
      1997 and May 2003. Patients were treated with rituximab alone or with a
      combination of rituximab and chemotherapy. The overall response rate (complete
      and partial response) was 73% for the second treatment. The median time to
      progression was longer but not significant for the second treatment in comparison
      with the first one (15.2 versus 11.3 months, P = 0.09). The second treatment was
      well tolerated. Thus, a second treatment with rituximab should be considered,
      alone or in combination with chemotherapy, for patients who progress after a
      first response to rituximab.

PMID- 15570287
TI  - Low-dose oral fludarabine plus cyclophosphamide in elderly patients with chronic
      lymphoproliferative disorders.
AB  - A synergistic effect of fludarabine (FLU) and cyclophosphamide (CY) has been
      extensively demonstrated in the treatment of chronic lymphoproliferative
      disorders (CLD), although a high incidence of severe neutropenia and infectious
      complications, particularly in elderly patients, have been reported. Based on a
      previous clinical experience in elderly CLD patients treated with a combination
      of low-dose intravenous (i.v.) FLU and CY in whom we obtained good response rates
      and negligible toxicity, we tested efficacy and safety of the new oral
      formulation of FLU combined with CY at low doses. A total of 28 elderly patients
      with relapsed/refractory or untreated CLD were treated with oral FLU and CY (25
      and 150 mg/m2 respectively, both for 4 days every 4 weeks). The treatment design
      consisted in four consecutive courses and the median value of courses per patient
      was 3. Overall, 25 out of 28 evaluable patients were responsive to the treatment
      (six CR and 19 PR; ORR 89%), while the remaining three patients did not show any
      appreciable response (two progressive and one stable disease). Hematological
      toxicity was low in the majority of patients (grade 2-3 neutropenia/anemia in
      8/28 cases); however, two fatal infections occurred and one additional patient
      died because of disease progression. Extra-hematological toxicity was generally
      mild. This preliminary report suggests that oral combination of FLU and CY at low
      dose is effective as the i.v. formulation and standard doses, since it may induce
      rapid responses in about 90% of elderly patients with CLD, with an acceptable
      toxicity.

PMID- 15570288
TI  - Effectiveness and safety of combined iron-chelation therapy with deferoxamine and
      deferiprone.
AB  - INTRODUCTION: The purpose of our study was to evaluate the effectiveness and
      safety of combined therapy with deferoxamine (DFO) and deferiprone (DFP) in
      patients with beta-thalassemia major and increased serum ferritin. PATIENTS AND
      METHODS: Our study was performed in 36 patients with beta-thalassemia major. DFP
      was administered orally in a total daily dose of 60 mg/kg for 6 days per week and
      DFO was administered subcutaneously in a total daily dose of 40-50 mg/kg for 4-6
      days per week. The efficacy of combined treatment was assessed by measurements of
      serum ferritin and 24-h urine iron excretion levels. RESULTS: Out of the 36
      patients, 11 discontinued DFO after a mean of 4 months; however, 25 patients, who
      continued to receive the combined therapy showed a very satisfactory compliance.
      After a mean of 13.5 months, their mean serum ferritin levels reduced from 2637 +
      1292 to 1580 + 1024 ng/ml (P = 0.002) and their mean urinary iron excretion
      elevated from 0.41 + 0.27 to 0.76 +0.49 mg/24h (P = 0.003). The observed side
      effects were gastrointestinal disorders,elevations in liver enzymes, mild
      neutropenia, joint symptoms, taste disorders, dizziness and fatigue. CONCLUSIONS:
      The results of this study show that combined iron-chelation therapy with DFO and
      DFP results in satisfactory reduction of serum ferritin with no significant
      toxicity.

PMID- 15570289
TI  - Bone remodelation markers are useful in the management of monoclonal
      gammopathies.
AB  - The evaluation of bone disease in multiple myeloma (MM) by conventional radiology
      has low reproducibility. In the last decade, several serum and urine biochemical
      parameters, for evaluation of bone turnover, have become available. The present
      study was designed to explore the value of six bone remodelation markers. It was
      studied in a series of 176 newly diagnosed patients with monoclonal gammopathies
      (107 MM and 69 monoclonal gammopathies of unknown significance (MGUS)). As
      control groups we used 25 patients with benign osteoporosis (BO) and 32 healthy
      individuals (HI). The bone markers analyzed included: bone resorption markers
      (BRM) (total pyridinoline, total deoxypyridinoline, free deoxypyridinoline and C
      terminal telopeptide of collagen I) and bone formation markers (BFM) (bone
      alkaline phosphatase (bAP) and osteocalcin (OC)). Serum or urinary levels of BRM
      were significantly higher in MM patients than in MGUS patients, BO patients or HI
      (P < 0.001, respectively). BRM were higher in MM patients with lytic lesions.
      However, only C-terminal telopeptide discriminated MM patients without bone
      lesions from MGUS patients. BFM did not show significant differences in the
      aforementioned comparisons, although a trend toward higher values of OC and lower
      values of bAP in patients with early bone affectation was observed. Ratios
      BRM/BFM that contained bAP exhibited differences that were most significant
      between the MM group and other entities, as well as between the different MM
      subgroups. In fact, the ratios BRM/bAP provided discrimination between the MM
      subgroup without lyses and MGUS group (P < 0.01). BRM and BFM, especially the
      ratios, are useful in the evaluation of bone lesions in patients with monoclonal
      gammopathies.

PMID- 15570290
TI  - XIAP expression correlates with monocytic differentiation in adult de novo AML:
      impact on prognosis.
AB  - Antiapoptotic proteins like the inhibitor of apoptosis proteins (IAPs) are
      molecular markers potentially useful for the characterization of acute myeloid
      leukemia (AML). We screened 92 adults with de novo AML for the protein expression
      of various IAPs, Bcl-2 family members and the proform of Caspase-3 using
      quantitative immunoblot and flow cytometry. XIAP expression correlated with
      myelomonocytic French-American-British (FAB) subtypes M4/M5 (P < 0.05) and
      expression of monocytic markers (CD 14, CD 36; P < 0.05; CD 4, HLA-DR; P < 0.01)
      in AML blasts. In addition, XIAP was overexpressed in normal monocytes but
      undetectable in granulocytes. In AML, XIAP expression was significantly lower in
      patients with favorable than intermediate or poor cytogenetics (n = 74; P <
      0.05). In total, 62 of the examined patients were treated according to the German
      AML Cooperative Group (AMLCG) 92 protocol. These patients were analyzed for
      prognostic significance of apoptosis-related proteins. Patients expressing low
      levels of XIAP enjoyed better overall survival than patients expressing high
      amounts of XIAP (mean, 9 (n = 41) versus 19 months (n = 21); P < 0.05). Other
      IAPs, most importantly Survivin, were of no prognostic value. We conclude that
      XIAP but not other IAP family members is associated with monocytic
      differentiation in normal and malignant myelopoiesis, and may be of prognostic
      significance for overall survival in adult de novo AML.

PMID- 15570291
TI  - p-Iodophenol-enhanced luminol chemiluminescent assay applied to discrimination
      between acute lymphoblastic and minimally differentiated acute myeloid (FAB-M0)
      or acute megakaryoblastic (FAB-M7) leukemias.
AB  - INTRODUCTION: In this report, we propose the application of the p-iodophenol
      enhanced luminol chemiluminescent technique to the determination of peroxidase
      (myeloperoxidase and/or platelet peroxidase) activity in blasts of minimally
      differentiated acute myeloblastic leukemia (AML-M0) and acute megakaryoblastic
      leukemia (AML-M7). METHODS: The frozen blast cells from 29 patients were thawed
      and submitted to the optimized protocol. RESULTS: All cases of AML-M7 and AML-M I
      exhibited integrated light emission greater than 73(10(2) mV x s), which was the
      arbitrary cutoff point set for the discrimination between AML and acute
      lymphoblastic leukemia (ALL) (mean + 3 x s.d. of ALL samples, n = 10). In
      addition, five out of seven cases of AML-MO showed results above the cutoff
      point. CONCLUSION: This highly sensitive enhanced chemiluminescent technique may
      be applied to discriminate between ALL and AML-M7 or AML-MI cases, and most AML
      M0 cases. It is very simple, cheap and easy to perform compared to other
      procedures used to measure MPO activity in AML-leukemias including AML-M7 and AML
      M0.

PMID- 15570292
TI  - Glutathione sulfur transferase M1 and T1 genotypes in chronic lymphoblastic
      leukemia.
AB  - Glutathione sulfur transferases (GSTs) is a group of enzymes involved in the
      detoxification process of carcinogens and other substances. The genes encoding
      isoenzymes M1 and T1 are polymorphic in humans and the phenotypic absence of
      enzyme activity (null genotype) may have an effect on the risk of chronic
      lymphoblastic leukemia (CLL). Our purpose was to examine whether the GSTM1 and
      GSTT1 homozygous null genotypes altered the risk of CLL. DNA was extracted from
      the peripheral blood of 27 patients with CLL and 147 cancer-free controls; both
      groups originated from a defined population (residents of the Ioannina region,
      northwestern Greece) and were similar with regard to mean age, race and sex;
      GSTM1 and GSTT1 were simultaneously analyzed by a multiplex polymerase chain
      reaction (PCR) method and Fisher's exact test was used for comparisons between
      the two groups. A significantly increased incidence of the GSTM1 null genotype
      was found in the group of patients compared to the controls (74.07 versus 34.69%,
      P = 0.0002). Additionally, the incidence of the GSTT1 null genotype was
      comparable in patients and controls (25.92 versus 10.20%, P = 0.05). The
      frequency of the combined GSTM1 null/T1 null genotype was significantly different
      between patients and controls (14.81 versus 2.04%, P = 0.012). However, there was
      no relationship between the advanced stage of the disease and the GSTs status.
      Individuals with the GSTM1 and GSTT1 null genotypes may have enhanced
      susceptibility to CLL.

PMID- 15570293
TI  - Upregulated production of IL-6, but not IL-10, by interferon-alpha induces SOCS3
      expression and attenuates STAT1 phosphorylation in myeloma cells.
AB  - Interferon-alpha (IFN-alpha) is used as a treatment for multiple myeloma,
      although its clinical effects remain controversial. Here, we investigated whether
      IFN-alpha altered the autocrine production of interleukin-6 (IL-6) or IL-10, both
      identified as key cytokines regulating myeloma cell growth/survival, and found
      that IL-6, but not IL-10, induced by IFN-alpha attenuated IFN-alpha-mediated
      signaling in myeloma cells via an upregulated SOCS3. Using reverse transcription
      polymerase chain reaction, expression of the IL-6 gene (IL-6) and IL-10 was
      detected in two and three of eight myeloma cell lines, respectively. When myeloma
      cells were cultured with IFN-alpha, an increase of IL-6 and IL-10 production was
      detected in IL-6-expressing and in IL-10-expressing cells, respectively. IFN
      alpha inhibited the cell growth of these myeloma lines. Addition of an IL-6
      neutralizing antibody prolonged the phosphorylation of STAT1 induced by IFN-alpha
      and significantly enhanced the cell growth suppression of IFN-alpha on IL-6
      expressing cells. However, a similar blocking of IL-10 in the presence of IFN
      alpha did not affect the growth/survival of IL-10-expressing cells.
      Interestingly, exogenous IL-6, but not IL-10, induced high levels of SOCS3
      expression. Although upregulation of SOCS3 was also observed in the presence of
      IFN-alpha alone in IL-6-expressing cells, this expression was completely
      abrogated by the IL-6-neutralizing antibody. The L929 cell line transfected with
      SOCS3 showed the protection from the growth suppression of IFN-alpha. These
      results suggest that IL-6 induced by IFN-alpha plays an important role in the
      growth/survival of myeloma cells via an autocrine loop, and upregulated SOCS3 by
      IL-6 may be at least partially responsible for the IL-6-mediated inhibition of
      IFN-alpha signaling in myeloma cells.

PMID- 15570294
TI  - In malignant myeloid cells expression of Daxx downregulates expression of p53 and
      of the inhibitors of apoptosis proteins.
AB  - The role of Daxx, in particular its ability to promote or hinder proliferation,
      still remains controversial. In order to elucidate the functional relevance of
      Daxx in malignant myelocytes, the erythroleukemia cell line HEL was stably
      transfected with a Daxx-expressing vector or with the respective Daxx-negative
      control vector. Assessing the molecular consequences of ectopic Daxx-expression,
      we present evidence that Daxx downregulates p53. Moreover, we demonstrate that
      Daxx overexpressing myelocytes downregulate the proapoptotic Bcl-2 family member
      Bax, while expression of antiapoptotic Bcl-2 is not influenced. Furthermore,
      expression of Daxx diminishes expression levels of the initiator-procaspase-8 and
      -10, and the executioner procaspase-7, whereas the procaspase-3, -6 and -9 remain
      unaltered. The altered protein levels of the caspases in Daxx overexpressing
      myelocytes are accompanied by a decrease of expression levels of the inhibitor of
      apoptosis proteins (IAPs) cIAP-1, -2 and survivin. Despite the described impact
      of Daxx expression on major molecules of the apoptotic cascade, expression of
      Daxx in neoplastic myelocytes does not impact on the rate of proliferation. Upon
      a proapoptotic stimulus such as serum withdrawal Daxx is unable to maintain its
      influence on expression levels of p53, Bax, IAPs and the procaspase-8, -10 and 
      7.

PMID- 15570295
TI  - Effect of adenovirus-mediated p27 gene expression on the proliferation and
      apoptosis of HL-60 and Raji cell lines.
AB  - OBJECTIVE: To explore the possible effect of p27 gene expression on the
      proliferation and apoptosis of HL-60 and Raji cell lines. METHODS: The infections
      of HL-60 and Raji cells were performed by the adenovirus-mediated p27 gene
      transfection approach. The efficiency of Adp27 infection and the expression of
      p27 mRNA and protein were evaluated by X-gal staining, RT-PCR and flow cytometry.
      The proliferation and apoptosis of HL-60 and Raji cells were estimated by using
      trypan blue staining, MTT assay, Annexin V/PI and DNA ladder electrophoresis.
      RESULTS: The infection efficiency of HL-60 and Raji cells were 40.3 and 32%,
      respectively; RT-PCR and flow cytometry showed that there were significant
      expressions of p27 mRNA and protein of HL-60 and Raji cells infected by Adp27,
      while HL-60 cells themselves showed only faint p27 mRNA and protein, and Raji
      cells hardly presented p27 mRNA and protein. The strong proliferation
      inhibitions, which were in a time-dependent manner for HL-60 and Raji cells
      infected by Adp27, were indicated by cell growth curve and MTT assay. After 72 h
      infection of HL-60 and Raji cells by Adp27, the Annexin V+/PI- apoptotic cell
      rates were 46.9 and 35.7% respectively, which were significantly increased
      compared with control group (4.7 and 5.6% respectively). The typical DNA ladder
      bands were detectable in HL-60 and Raji cells after 48 h of Adp27 infection.
      CONCLUSION: The infection of HL-60 and Raji cells by means of adenoviral vector
      mediated p27 gene could evidently inhibit cellular proliferation and promote cell
      apoptosis, which would provide experimental evidence for gene therapy of
      leukemia/lymphoma using adenovirus-mediated p27 gene approach.

PMID- 15570296
TI  - Spectrum and haplotypes of the HFE hemochromatosis gene in Iran: H63D in beta
      thalassemia major and the first E277K homozygous.
AB  - We present the molecular analysis of HFE gene in 400 Southwest Iranian
      individuals. We have studied 43 newborn, selected for the presence of HbBart's at
      birth, 203 normal adult and 154 transfused patients affected with beta
      thalassemia. Mutation analysis consisted of amplification and direct sequencing
      using two different pairs of forward and reverse primers. The C282Y and S65C
      mutations were not found. The H63D mutation was present with an allele frequency
      of 0.10 in newborns, 0.082 in normal adults and 0.080 in the beta-thalassemia
      major populations, respectively. No differences were found between normal adults
      and thalassemia major patients suggesting that this mutation does not increase
      mortality in beta-thalassemia. The H63D mutation was found associated with
      haplotype VI in 41% of the chromosomes. Other haplotypes were found suggesting a
      multicentric origin rather than a single mutation of European origin. While
      sequencing exon 4, a G --> A transition was found in the proximity of the C282Y
      mutation. The effect of this single base substitution (E277K) previously reported
      in an Asian individual and now found in homozygous form in a young transfused and
      chelated homozygous beta-thalassemia patient is not yet known.

PMID- 15570297
TI  - Acute tumour lysis syndrome after oral fludarabine in a patient with chronic
      lymphocytic leukaemia.
AB  - Acute tumour lysis syndrome (TLS) is a very rare complication of cytotoxic
      therapy in patients with chronic lymphocytic leukaemia (CLL). We report a patient
      with CLL who developed tumour lysis syndrome twice after oral fludarabine
      therapy. Both times TLS developed more than 2 weeks after the initiation of
      therapy. To our knowledge this is the first reported case of TLS in CLL
      precipitated by oral fludarabine.

PMID- 15570298
TI  - Long-lasting remission of primary hepatic lymphoma and hepatitis C virus
      infection achieved by the alpha-interferon treatment.
AB  - Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often
      pursues an aggressive clinical course. Most cases have been described in
      hepatitis C virus (HCV)-related chronic liver disease patients. Although
      anthracycline-based chemotherapy has been reported to be highly effective, the
      best therapeutic strategy has not been defined yet. The prognosis is dismal
      especially in patients treated with chemotherapy alone or when an advanced liver
      disease is present. Herein, we describe a case of primary hepatic large B-cell
      non-Hodgkin's lymphoma, in a patient with HCV chronic infection. After a minor
      response with eight cycles of CHOP chemotherapy, a complete and sustained
      remission was obtained with alpha-interferon at the daily dose of 3 MU. HCV-RNA
      clearance pace from the blood almost paralleled the response of the lymphoma and
      both diseases went in remission within 1 year of therapy. The possible place of
      alpha-Interferon in the treatment of primary hepatic lymphoma is discussed.

PMID- 15570299
TI  - Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1
      fusion: two further cases.
AB  - We report two new cases with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion. Case 1
      presented with polycythaemia vera (PV) and evolved over 4 years to a
      myeloproliferative disorder (MPD) resembling the 8p11 myeloproliferative syndrome
      (EMS). Case 2 presented with B-cell lymphoblastic leukaemia (B-ALL). These cases
      illustrate the clinical heterogeneity observed in patients with FGFR1
      rearrangements and suggest that constitutively activated tyrosine kinases may be
      more widespread in MPDs.

PMID- 15570300
TI  - Immune-mediated thrombocytopenic purpura associated with Toxoplasma gondii
      infection in an immunocompetent patient.
AB  - Infection with Toxoplasma gondii (T. gondii) in immunocompetent adults is usually
      asymptomatic and needs no specific therapy. We report the case of a 16-year-old
      previous healthy adolescent who presented with bleeding due to immune-mediated
      thrombocytopenic purpura during an acute acquired T. gondii infection. Treatment
      with prednisolone and immunoglobulin resulted in a relative increase in the
      platelet count. Taking into account the fact that the patient became
      immunocompromised under corticosteroids, specific antitoxoplasmal treatment has
      been added. The difficulties in treatment decision in this rare case are
      discussed.

PMID- 15570301
TI  - Heterozygous prothrombin 20210G/A mutation, associated with hyperhomocysteinemia,
      and homozygous methylenetetrahydrofolate reductase 677C/T mutation, in a patient
      with portal and mesenteric venous thrombosis.
AB  - We herein report a 34-year-old man who was investigated for severe abdominal
      pain. Portal vein thrombosis (PVT) and mesenteric vein thrombosis (MVT) were
      diagnosed. An association with two predisposing factors for thrombosis was noted:
      (1) heterozygous factor II 20210G/A mutation and (2) homozygous
      methylenetetrahydrofolate reductase (MTHFR) 677C/T mutation with
      hyperhomocysteinemia. Our case is of particular interest because the patient
      reported herein, is homozygote for the MTHFR 677C/T mutation, while the only two
      other cases reported in the literature with similar gene mutations, were
      heterozygotes for the mutation.

PMID- 15570302
TI  - Unexpectedly high but still asymptomatic iron overload in a patient with pyruvate
      kinase deficiency.
AB  - Iron overload is a serious condition, which may lead to irreversible organ
      damage. The risk of iron accumulation in pyruvate kinase deficiency (PKD) has
      traditionally been regarded as low, but recent evidence has questioned this
      notion. We here present a case of a young PKD patient showing evidence of
      asymptomatic iron accumulation measured as liver iron concentration (LIC)
      obtained noninvasively by magnetic resonance imaging. The iron overload was not
      related to blood transfusions, but rather secondary to concomitant risk factors
      leading to increased intestinal iron absorption, such as chronic hemolysis and
      splenectomy. The iron status of PKD patients, preferably assessed by LIC
      measurements, should therefore be evaluated regularly also in asymptomatic
      patients. This evaluation should start already at a young age, in order to
      initiate iron chelation before the development of iron-induced organ damage.

PMID- 15570303
TI  - Anti-CD20 monoclonal antibody rituximab for the treatment of B-cell chronic
      lymphocytic leukemia-associated pure red cell aplasia.

PMID- 15570304
TI  - An epidemic of invasive fungal infection in a stem cell transplant unit; response
      to high-dose liposomal amphotericin B.

PMID- 15570305
TI  - Coexistence of treatment-related MLL cleavage and rearrangement in a child with
      haemophagocytic lymphohistiocytosis.
AB  - Treatment-related acute myeloid leukaemia (t-AML) is a serious complication of
      topoisomerase 2 inhibitor therapy and is characterised by the presence of mixed
      lineage leukaemia (MLL) rearrangement. By molecular tracking, we were able to
      show that MLL cleavage preceded gene rearrangement by 3 months and before the
      clinical diagnosis of t-AML in a patient with haemophagocytic
      lymphohistiocytosis. This is the first report on the sequential detection of the
      two biomarkers in treatment-related leukaemogenesis.

PMID- 15570306
TI  - Classic Kaposi's sarcoma in Italy, 1985-1998.
AB  - To evaluate incidence rates (IRs) of classic Kaposi's sarcoma (CKS) in Italy
      after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using
      an 'ad hoc' record linkage procedure between 15 Cancer Registries (CRs) (21% of
      the Italian population) and the national AIDS Registry. Between 1985 and 1998,
      874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS
      accounted for 16 and 27% of KS cases below 55 years of age in men and women,
      respectively, but for 91 and 100% of those above age 55. The IRs for CKS were
      1.0/ in men and 0.4/100,000 in women, but they varied between 0.3 in Umbria and
      4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs
      of CKS in both genders were stable between 1985-1987 and 1993-1998. In Northern
      and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in
      individuals born in the same area, but 1.6 in individuals born in Southern Italy
      or in the Islands (rate ratio = 3.2) suggesting that KS-associated herpesvirus,
      the cause of KS, is acquired early in life.

PMID- 15570307
TI  - Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer:
      re-induction of endocrine sensitivity an unexpected finding.
AB  - The management of androgen independent prostate cancer is increasingly disputed.
      Diethylstilbestrol and steroids have useful second-line activity in its
      management. The value of chemotherapy still remains contentious. This paper
      reports a phase 2 study of two orally active chemotherapy drugs in patients who
      are absolutely hormone refractory having failed primary androgen blockade and
      combined oestrogens and corticosteroids. In total, 37 patients who were
      biochemically castrate with absolute hormone refractory prostate cancer and
      performance status of 0-3 were enrolled. Therapy consisted of chlorambucil 1 mg
      kg(-1) given as 6 mg a day until the total dose was reached and lomustine 2 mg
      kg(-1) given every 56 days (CL56). During this time all hormone therapy was
      stopped. One patient normalised his PSA with a further two having a greater than
      50% decline leading to an objective response rate of 10%. The median time to
      progression was 3.6 months with an overall survival of 7.1 months. The median
      survival of this group of patients from first becoming androgen independent was
      23.5 months. Eight of 17 (47%) patients who were subsequently re-challenged with
      hormonal therapy following failure of chemotherapy had a further PSA reduction,
      three (17%) of which were >50%. The median progression-free interval for the
      eight patients was 4 months. In conclusion, CL56 has a low objective response
      rate in the management of absolute hormone refractory prostate cancer. Toxicity
      was mild. Re-induction of hormone sensitivity following failure of chemotherapy
      was an unexpected finding that requires further study.

PMID- 15570308
TI  - The role of human papillomavirus type 16 and the fragile histidine triad gene in
      the outcome of cervical neoplastic lesions.
AB  - The presence of high-risk human papillomavirus, loss of heterozygosity on
      chromosome 3p and fragile histidine triad gene expression were assessed as
      potential markers of cancer and CIN progression in 83 cervical cancers and 74
      cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16
      was an indicator of vascular involvement in cancers. Loss of heterozygosity,
      especially in the fragile histidine triad gene intron 5, was an indicator of high
      grade tumours, greater tumour depth and lymph node involvement. Abnormal fragile
      histidine triad gene expression was more frequent in cervical intraepithelial
      neoplasia grade 1 lesions with increased risk of disease progression.

PMID- 15570309
TI  - Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a
      population covered by national mammographic screening.
AB  - Sweden was the first country to establish a nationwide breast cancer screening
      service. We used the Swedish Family-Cancer Database to evaluate the risk of
      invasive carcinoma after in situ carcinoma of the breast. Risk estimates for
      contralateral and ipsilateral invasive malignancies following age and histology
      specific in situ breast carcinomas were calculated using Poisson's regression
      analysis. The agreement between concordant and discordant morphologies of
      invasive and in situ breast cancer was measured using the kappa statistic. Women
      with in situ breast cancer showed a relative risk of 2.03 for contralateral and
      3.94 for ipsilateral invasive breast cancer. The risk was higher for in situ
      carcinomas diagnosed before the age of 50 years and after lobular in situ breast
      cancers. A comparison of the risks during the past decades suggested that the
      risk of ipsilateral breast cancer has increased in Sweden but that of
      contralateral breast cancer has remained unchanged. In situ and the subsequent
      invasive breast cancers did not seem to share their morphologies.

PMID- 15570310
TI  - The relationship between circulating concentrations of C-reactive protein,
      inflammatory cytokines and cytokine receptors in patients with non-small-cell
      lung cancer.
AB  - The relationship between circulating C-reactive protein concentrations and
      potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory
      factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble
      gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8
      (IL-8)) of this acute phase protein were examined in healthy subjects (n=11) and
      patients with non-small-cell lung cancer (n=50). Leukaemia inhibitory factor and
      CNTF were below detection limits in all controls and patients. C-reactive
      protein, interleukin-6, soluble gp130, soluble TNF receptor, interleukin-1
      receptor antagonist and IL-8 concentrations were significantly elevated in cancer
      patients (P< or =0.001). Cancer patients with elevated C-reactive protein
      concentrations had greater concentrations of interleukin-6 (P<0.01) and
      interleukin-1 receptor antagonist (P<0.05). On regression analysis only
      interleukin-6 was independently associated with C-reactive protein (r=0.616,
      P<0.001). Interleukin-6 is an important independent mediator of elevated C
      reactive protein concentrations in patients with non-small-cell lung cancer.

PMID- 15570311
TI  - Long-chain fatty acid uptake is upregulated in omental adipocytes from patients
      undergoing bariatric surgery for obesity.
AB  - OBJECTIVE: To determine the impact of obesity on adipocyte cell size and long
      chain fatty acid (LCFA) uptake kinetics in human subjects undergoing laparoscopic
      abdominal surgery. SUBJECTS: A total of 10 obese patients (BMI 49.8+/-11.9 (s.d.)
      kg/m(2)) undergoing laparoscopic bariatric surgery, and 10 nonobese subjects (BMI
      24.2+/-2.3 kg/m(2)) undergoing other clinically indicated laparoscopic abdominal
      surgical procedures. MEASUREMENTS: Cell size distribution and [(3)H]oleic acid
      uptake kinetics were studied in adipocytes isolated from omental fat biopsies
      obtained during surgery. Adipocyte surface area (SA) was calculated from the
      measured cell diameters. Plasma leptin and insulin concentrations were measured
      by RIA in fasting blood samples obtained on the morning of surgery. RESULTS: The
      mean SA of obese adipocytes (41 508+/-5381 mu(2)/cell) was increased 2.4-fold
      compared to that of nonobese adipocytes (16 928+/-6529 mu(2)/cell; P<0.01). LCFA
      uptake in each group was the sum of saturable and nonsaturable components. Both
      the V(max) of the saturable component (21.3+/-6.3 vs 5.1+/-1.9 pmol/s/50,000
      cells) and the rate constant k of the nonsaturable component (0.015+/-0.002 vs
      0.0066+/-0.0023 ml/s/50 000 cells) were increased (P<0.001) in obese adipocytes
      compared with nonobese controls. When expressed relative to cell size,
      V(max)/mu(2) SA was greater in obese than nonobese adipocytes (P<0.05), whereas
      k/mu(2) SA did not differ between the groups. CONCLUSION: The data support the
      concepts that (1) adipocyte LCFA uptake consists of distinct facilitated
      (saturable) and diffusive processes; (2) increased saturable LCFA uptake in obese
      adipocytes is not simply a consequence of increased cell size, but rather
      reflects upregulation of a facilitated transport process; and (3) the
      permeability of adipocyte plasma membranes to LCFA is not appreciably altered by
      obesity, and increased nonsaturable uptake in obese adipocytes principally
      reflects an increase in cell SA. Regulation of saturable LCFA uptake by
      adipocytes may be an important control point for body adiposity.

PMID- 15570312
TI  - BMI, waist-circumference and waist-hip-ratio as diagnostic tests for fatness in
      adolescents.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of body mass index (BMI, kg/m(2)),
      waist-circumference (WC) and waist-hip-ratio (WHR) as diagnostic tests for
      detecting fatness in adolescents. DESIGN: A cross-sectional analysis of 474
      healthy adolescents aged 17 y was used. Measurements of height, weight, WC, hip
      circumference and body fat percentage (%BF) were obtained. The diagnostic
      accuracy for detecting excess fatness was evaluated through receiver operating
      characteristics (ROC) analyses with %BF, measured by densitometry (air
      displacement plethysmography), as reference test. RESULTS: BMI and WC showed
      strong positive correlation (r=0.68-0.73; P<0.0001) with %BF in both sexes, but
      the correlation was weaker for WHR (r=0.30-0.41; P<0.0001). For overweight and
      obesity in boys and obesity in girls, the area under the ROC curve was high (0.96
      0.99) for BMI and WC. WHR was not significantly better than chance as diagnostic
      test for obesity in girls. For BMI and WC, highly sensitive and specific cutoffs
      for obesity could be derived, while larger trade-offs were needed for detecting
      overweight in girls. The cutoffs producing equal sensitivity and specificity were
      lower than the ones minimizing the absolute number of misclassifications. The
      latter approached internationally recommended reference values, but were still
      several units lower for BMI in girls and several centimeters lower for WC in
      boys. CONCLUSION: BMI and WC were found to perform well as diagnostic tests for
      fatness, while WHR was less useful. The discrepancies between cutoffs producing
      equal sensitivity and specificity, cutoffs minimizing the absolute number of
      misclassifications and internationally recommended reference values for
      overweight and obesity highlight the importance of specifying the characteristics
      of classification systems for different settings.

PMID- 15570313
TI  - Trends in waist circumferences in young British children: a comparative study.
AB  - OBJECTIVE: To compare waist circumference (a measure of central fatness) and body
      mass index (BMI, a measure of general fatness) between a contemporary cohort and
      similar aged British children measured in 1987. DESIGN: : Comparative study of
      two cohorts. The first was a cross-sectional survey and the second an ongoing
      longitudinal survey. SETTING: : The cross-sectional study was conducted
      throughout Great Britain during 1987. The ongoing longitudinal study was
      conducted in the Avon region between 1995 and 1998. PARTICIPANTS: A total of 1821
      children were measured in the cross-sectional study, and around 1000 children
      were measured in the longitudinal study. Ages ranged between 2 and 5 y. MAIN
      OUTCOME MEASURES: Waist circumference, height, weight and BMI. Values were
      expressed as mean+/-s.d. Age-related measures were compared. RESULTS: At
      equivalent ages, mean waist circumference values were greater in the contemporary
      children, compared with children measured in the earlier cross-sectional study in
      1987 (P<0.05). Although boys from the contemporary cohort had the larger absolute
      waist circumference measurements, the absolute and percentage differences in
      waist circumference between the cohorts were greater for the girls. Mean BMI
      values were slightly but significantly higher in the contemporary children
      compared with children measured in the earlier cross-sectional study (P<0.05).
      The proportional increase in waist circumference for each age-sex group generally
      exceeded the proportional increase in BMI. CONCLUSION: These results suggest that
      central fatness in young British children has increased over the period of 1987
      97 to a greater extent than general fatness. This should be of concern since
      evidence associates greater central adiposity with adverse levels of
      cardiovascular risk factors in children. Furthermore, the study highlights
      important shortcomings of the BMI measurement, in that it provides no information
      on body fat distribution and can mask true obesity-related risk in children.

PMID- 15570314
TI  - Vascular endothelial dysfunction tested by blunted response to endothelium
      dependent vasodilation by salbutamol and its related factors in uncomplicated pre
      menopausal obese women.
AB  - BACKGROUND: Vascular endothelial dysfunction (VED) plays a pivotal role in the
      pathogenesis of atherosclerosis and is associated with insulin resistance and
      visceral obesity. We examined the predicting factors of VED in uncomplicated
      premenopausal obese women using analysis of endothelium-dependent vasodilation by
      radial artery pulse wave obtained through applanation tonometry. METHODS: The
      subjects included a group of 33 obese women body mass index ((BMI) > or = 25) and
      another age-matched control group of 25 nonobese women (BMI: 18.5-22.9) of Asian
      origin. All uncomplicated premenopausal (20-45 y) obese women were sedentary (<1
      h/week of physical activity). Anthropometric measurements were performed, and
      regional distributions of adipose tissue and metabolic variables were measured.
      Endothelial function was measured by pulse wave analysis after salbutamol
      administration, which reflects endothelium-mediated vasodilation, contributed
      partially by nitric oxide release from beta2-adrenergic stimulation. Radial
      artery wave forms were recorded and from a derived aortic wave forms augmentation
      index (AIx, defined as the pressure difference between the first and second peaks
      of the central arterial wave form, expressed as a percentage of the pulse
      pressure) was calculated. The subjects received sublingual nitroglycerine (NTG)
      (0.6 mg), followed by nebulized salbutamol (2.5 mg). RESULTS: AIx fell
      significantly after the administration of salbutamol, which causes endothelium
      dependent vasodilatation. This value was significantly reduced in obese women
      compared with the controls (10.3+/-6.7 vs 17.2+/-6.8%, P=0.0003). NTG, which
      causes endothelium-independent vasodilatation, did not produce significant
      changes (P=0.917). As for our obese subjects, the visceral adipose tissue area
      was a significant predictor of VED independent of BMI, percent body fat, and
      other metabolic variables including high-sensitivity C-reactive protein (beta = 
      0.141, P=0.002, Adj-R(2)=0.41). CONCLUSION: Increased abdominal adiposity is a
      powerful independent predictor of VED in uncomplicated obese women. Further
      studies are warranted to determine the pathophysiological link between visceral
      adipose tissue and VED.

PMID- 15570315
TI  - Differences in the relationship between lipid CHD risk factors and body
      composition in Caucasians and Japanese.
AB  - OBJECTIVES: To examine differences in the relationship between fat distribution
      and lipid coronary risk factors in Caucasian and Japanese population and further
      to determine whether the cut-points for body mass index (BMI) and waist
      circumference (WC) proposed by WHO and NHLBI are applicable to Japanese
      population as a predictor of a lipid risk factor abnormality or not. RESEARCH
      METHODS AND PROCEDURES: Subjects were 895 participants of the Baltimore
      Longitudinal Study of Aging in the US (BLSA) and 1705 participants of the
      Longitudinal Study of Aging by the National Institutes for Longevity Science in
      Japan (NILS-LSA). Subjects were divided into four demographic groups as younger
      (age<65 y) men and women, and older (age> or =65 y) men and women. Blood total
      cholesterol, triglycerides, LDL- and HDL-cholesterol and anthropometry were
      measured. Regression coefficients of BMI and WC on risk factors, sensitivity and
      specificity of the BMI and WC cut-points for blood lipid abnormality, and mean
      values of blood lipids at BMI or WC cut-points were computed in both populations.
      RESULTS: Height, weight, WC and BMI were significantly greater in the BLSA than
      those in the NILS-LSA subjects. Total cholesterol, HDL- and LDL-cholesterol were
      significantly greater in the NILS-LSA than in the BLSA subjects. Sensitivities of
      BMI and WC cut-points were much lower in the NILS-LSA than in the BLSA subjects.
      Specificities of BMI and WC cut-points were higher in the NILS-LSA than in the
      BLSA subjects. Mean values of triglycerides, total cholesterol, HDL- and LDL
      cholesterol at BMI=25 were significantly greater in the NILS-LSA than in the BLSA
      subjects. At the WC cut-point (94 cm for men, 80 cm for women), mean values of
      all lipids were significantly greater in the NILS-LSA than in the BLSA subjects
      with the exception of triglycerides in younger women. CONCLUSIONS: The Japanese
      subjects have smaller BMI and WC, worse total and LDL-cholesterol levels and
      better HDL-cholesterol levels compared to Caucasians. Sensitivities of BMI and WC
      for predicting lipid risk factor abnormality are much lower in Japanese. The cut
      points for BMI and WC proposed by WHO and NHLBI may be too high for predicting an
      abnormality in triglycerides, total and LDL-cholesterol in Japanese. For
      detecting an abnormal HDL-cholesterol level, the BMI and WC cut-points may not be
      as beneficial for the Japanese population as for Caucasians.

PMID- 15570316
TI  - Absence of psychosis may influence linkage results for bipolar disorder.

PMID- 15570317
TI  - Pain following spinal cord injury: the impact on community reintegration.
AB  - STUDY DESIGN: Prospective, correlational. OBJECTIVES: (1) Describe how pain
      changes over recovery from admission to spinal cord injury (SCI) rehabilitation,
      discharge and after 6 months of community living and (2) examine the relationship
      between pain and community integration at 6 months of community living. SETTING:
      Tertiary rehabilitation centre, SCI unit, Vancouver, Canada. METHODS: Subjects
      from 66 consecutive admissions to the SCI Program of a tertiary rehabilitation
      centre for the treatment of a traumatic SCI during the years 2000-2002 were
      followed using data from the National Rehabilitation Reporting System (NRS).
      Information was obtained from NRRS standardized assessments performed on
      admission, discharge and 6 months of community living. Early community living was
      defined as 6 months postdischarge. Community reintegration was assessed by the
      Reintegration to Normal Living Index (RNL). Pain presence, pain impact and pain
      intensity were assessed using single item Likhert-type scales. RESULTS: In all,
      86% of individuals with a SCI reported pain at 6 months postdischarge, with 27%
      of these individuals reporting pain that impacted on many or most activities.
      Pain impact and pain intensity were related to the community reintegration (r = 
      0.39 and -0.55, P < 0.001), with pain intensity accounting for 25% of the
      variance in RNL scores. CONCLUSIONS: Pain is a major consequence of a SCI,
      impacting on an individual's activities and perception of how well they are
      integrated into the community. The results of this study highlight the need to
      address pain during both the rehabilitation phase of treatment and the early
      transition into the community.

PMID- 15570318
TI  - Semiquantitative assessment of hindlimb movement recovery without intervention in
      adult paraplegic mice.
AB  - STUDY DESIGN: Experimental laboratory investigation of hindlimb movement recovery
      in chronic paraplegic mice. OBJECTIVES: Development of an assessment method to
      discriminatively quantify motor and locomotor-like movements of paraplegic mice.
      SETTING: Laval University Medical Center, Quebec, Canada. METHODS: Signs of
      'functional recovery' were examined in open-field condition during 1 month in
      adult mice with a complete spinal cord transection at the low-thoracic level.
      RESULTS: None of the mice exhibited hindlimb movements after spinalization. At 7
      days, 33% of them displayed weak nonbilaterally alternating movements (NBA). At
      14 days, increased NBA were observed and the first bilaterally alternating
      movements (BA) in 10% of the mice. A progressive increase of movement frequency
      and amplitude was found after 2-3 weeks. By the end of the month, 86% displayed
      mixed NBA and BA. However, none of them recovered the ability to stand or bear
      their own weight with the hindlimbs. CONCLUSION: This study reports signs of
      partial hindlimb movement recovery in chronic paraplegic mice and provides
      evidence of plasticity in sublesional circuits of neurons occurring in the
      absence of inputs from the brain, locomotor training or pharmacological
      treatment. This assessment method can be used to characterize hindlimb movements
      in complete spinal cord transected mice tested in open-field condition.

PMID- 15570319
TI  - Effect of a phosphate supplement on urine pH in patients with neurogenic bladder
      receiving intermittent catheterization.
AB  - STUDY DESIGN: Pilot study; prospective design. SETTING: University Hospital,
      Virginia, USA. OBJECTIVE: To examine a phosphorus supplement as a urine
      acidifying agent in patients with neurogenic bladder on clean intermittent
      catheterization. METHODS: Seven patients were followed for 4 weeks. For the first
      week of study urine pH was measured three times a day: first morning urine
      sample, afternoon sample, evening sample. For the second and third weeks urine pH
      was measured and the patients drank a phosphorus supplement three times a day.
      For the fourth week of study the patients did not take the phosphorus supplement
      but the measurement of urine pH was continued. The patients were visited in their
      homes twice a week. During each visit a sample of urine was collected for
      culture. A supplement container count was performed and urine pH recordings were
      checked. RESULTS: There was no significant change in urine pH during the 2-week
      period when a patient was on phosphorus supplementation compared to when the
      patient was off supplementation. In addition, urine acidification was not
      achieved over the time period when urine pH was monitored. CONCLUSION: Phosphate
      supplementation had no effect on urine pH in patients with neurogenic bladder.

PMID- 15570320
TI  - Dermatological findings following acute traumatic spinal cord injury.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To identify and define dermatological
      conditions following acute traumatic spinal cord injury (ATSCI) during inpatient
      rehabilitation. SETTING: Spinal Cord Injury Unit, The Department of Neurological
      Rehabilitation, The Chaim Sheba Medical Center, Israel. METHODS: During a 1-year
      study, all patients following ATSCI were prospectively studied for new
      dermatological findings during their inpatient rehabilitation. Every new
      dermatological finding was defined concerning its location with regard to the
      patient's neurological level, the time from injury to appearance and the exact
      dermatological diagnosis. RESULTS: During the study year, 46 ATSCI patients were
      hospitalized in our department, of whom were 38 (82.6%) males and eight (17.4%)
      females (mean age 30.2 years). A total of 21 (45.6%) patients were tetraplegic
      and 25 (54.3%) paraplegic. Of the patients, 28 (60.9%) had complete neurological
      injuries and 18 (39.1%) incomplete. In all, 14 (30.4%) patients developed a
      dermatological condition. There was no significant age or sex correlation to the
      development of these complications. There was a greater likelihood of paraplegia
      (48 versus 9.5%, P=0.005) and being neurologically complete (42.9 versus 11.1%,
      P=0.02). The dermatological findings appeared on an average of 80.3 days after
      the initial neurological insult. There were a total of 22 different
      dermatological findings: 11 (50%) were local fungal infections, two (9.1%)
      psoriatic lesions, two (9.1%) hyperkeratotic lesions, two (9.1%) bacterial
      infections (one folliculitis, one impetigo) and single cases of seborrheic
      dermatitis, acne, alopecia, scabies and allergic reaction. Of the findings, 14
      (63.6%) were below the neurological level, including all of the fungal
      infections. CONCLUSIONS: Dermatological findings are common during rehabilitation
      of ATSCI. The clinical impact of these findings is low, but nevertheless, they
      are troublesome to the patient. The most common dermatological disorder was a
      local fungal infection below the neurological level. Paraplegic patients are more
      susceptible to the development of this condition. Patient and staff education
      regarding proper skin care may reduce these infections.

PMID- 15570321
TI  - Hormone replacement therapy in women with spinal cord injury - a survey with
      literature review.
AB  - STUDY DESIGN: Postal questionnaire survey. OBJECTIVE: To examine the current use
      of hormone replacement therapy (HRT) in a sample of menopausal women with spinal
      cord injury (SCI). SETTING: National Spinal Injuries Centre (NSIC), Stoke
      Mandeville Hospital, Aylesbury, UK. METHOD: A postal questionnaire was sent to 94
      women from the NSIC patient database who met the study inclusion criteria
      (wheelchair dependent, aged 49 years and above, last seen or heard from within
      the last 3 years). RESULTS: A total of 59 valid questionnaires were analysed. At
      the time of the survey, 50 women were menopausal and 11 of them were using HRT,
      six for menopausal symptoms and five for osteoporosis prevention. Another 11 had
      used HRT, eight for menopausal symptoms and three for osteoporosis prevention,
      but had discontinued it. The main reasons for stopping HRT were side effects. Of
      the 28 women who had never been on HRT, 20 had either enquired about it, or had
      been offered HRT, but decided against it. Of the nine women who were still
      premenopausal at the time of the survey, four would consider using HRT.
      CONCLUSIONS: Results show that 44% of the menopausal women in our sample have
      used HRT at some point and 22% still do, mostly for treatment of menopausal
      symptoms and for osteoporosis prevention. In view of the latest literature
      findings in able-bodied women, use of HRT for osteoporosis prevention in women
      with SCI may have to be reconsidered.

PMID- 15570322
TI  - Quality of sleep in individuals with spinal cord injury: a comparison between
      patients with and without pain.
AB  - STUDY DESIGN: A cross-sectional descriptive study of self-reported quality of
      sleep in individuals with a spinal cord injury (SCI). OBJECTIVES: To assess and
      describe subjective quality of sleep in patients with SCI, with and without pain.
      SETTING: Spinalis SCI unit, Stockholm, Sweden. METHODS: A total of 230 patients
      with an SCI were mailed a questionnaire containing queries about pain
      intensities, pain unpleasantness, mood, and sleep quality (Basic Nordic Sleep
      Questionnaire) to assess quality of sleep in patients with SCI with and without
      pain. RESULTS: Of the 192 questionnaires that were returned (response rate
      83.4%), 191 were analysed. Patients were divided into three groups: (1) those who
      reported no pain (n=50), (2) those who reported intermittent pain (n=42), and (3)
      those who suffered from continuous pain (n=99). Patients suffering from
      continuous pain rated pain intensity and unpleasantness significantly higher than
      those who only suffered from intermittent pain. The group with continuous pain
      also reported the poorest quality of sleep and the highest ratings of anxiety and
      depression of the three groups. Anxiety, together with pain intensity and
      depression, were the main predictors for poor sleep quality. CONCLUSIONS: Poor
      subjective sleep quality was associated with higher ratings of pain intensity,
      anxiety, and depression. It is possible that melatonin serves as a modulator of
      these different aspects.

PMID- 15570323
TI  - The Orewa Speech.

PMID- 15570324
TI  - Participation in small-group learning.

PMID- 15570325
TI  - Epidemiology of attempted suicide in Canterbury Province, New Zealand (1993
      2002).
AB  - AIMS: Non-fatal suicide attempts incur substantial costs in morbidity, subsequent
      mortality, and service utilisation. This study reviews trends in admissions to
      Christchurch Hospital for attempted suicide during the 10-year period 1993-2002,
      inclusive. The influences of age, gender, and method of suicide attempt on time
      trends were examined. METHODS: Participants were a consecutive series of 3711
      individuals admitted to Christchurch Hospital for attempted suicide from 1993 to
      2002. The following measures were available: age, gender, method of suicide
      attempt, and admission date. Logistic regression analysis was used to test trends
      over time. RESULTS The number of admissions for attempted suicide increased from
      1993 to 2002. Admissions increased for females (but not for males) and for those
      persons aged over 25. There was an increase in the number of admissions for
      female youth, but not for male youth or youth overall. Admissions for
      cutting/stabbing increased, while admissions for overdose/poisoning decreased.
      CONCLUSIONS: Trends observed at Christchurch Hospital for admissions for
      attempted suicide contrast with New Zealand's death by suicide rate, which has
      declined slightly over the last decade. Increases in attempted suicide admissions
      in adults, older adults, and females highlight the need for intervention
      strategies to be targeted at both males and females of all ages.

PMID- 15570326
TI  - Tutorial dynamics and participation in small groups: a student perspective in a
      multicultural setting.
AB  - AIM: This study investigated the language and cultural backgrounds of medical
      students, and explored their perspectives of the influences on student
      participation in small-group tutorial settings. METHOD: A task group of students
      and staff from a variety of cultural backgrounds designed a cross-sectional
      survey using an anonymous questionnaire. The survey was conducted at the
      Christchurch School of Medicine and Health Sciences (a campus of the University
      of Otago). Students attending a 4th-year and a 5th-year lecture were invited to
      participate. RESULTS: Seventy-five percent of students enrolled in the medical
      course responded to the survey. Half of the sample self-identified as New Zealand
      European or Maori. Sixty-four percent of students identified English as their
      first language. Ninety-one percent of students stated a preference for small
      group tutorials rather than lectures. Most students reported that there was a
      'lack of prior preparation' by students in these tutorials (no statistically
      significant difference between students with English as first or second
      language). Two thirds of students (66%) students felt there was a lack of full
      participation in small-group teaching. Personality, cultural, and language
      differences were perceived as contributing factors to the lack of participation.
      CONCLUSIONS: Lack of participation should not be assumed to be due to language
      difficulties. Barriers to participation are perceived differently by students
      from a variety of language and cultural backgrounds. Moreover, interactions
      between students who dominate and under-participate may influence student
      participation. Further research is needed to determine whether language and
      cultural backgrounds affect students' participation in small group teaching.

PMID- 15570327
TI  - Kava update: a European perspective.

PMID- 15570328
TI  - Salmonella Brandenburg: changing patterns of disease in Southland Province, New
      Zealand.
AB  - BACKGROUND: Salmonella Brandenburg has previously been an infrequent human
      pathogen in New Zealand, however a marked increase in human isolates has been
      noted since 1996. AIM: To research the incidence and pattern of Salmonella
      Brandenburg infection in New Zealand and specifically the characteristics of
      human isolates seen at Southland Hospital, Invercargill, Southland Province, New
      Zealand. METHODS: A literature review was performed, and statistical data from
      the Enteric Reference Laboratory, Institute of Environmental Science and Research
      Limited (ESR) was reviewed. A retrospective case series was performed, collecting
      demographic and clinical information for all patients with salmonellosis seen at
      Southland Hospital between September 1997 and May 2002. RESULTS: Salmonella
      Brandenburg is shown to have become the predominant human isolate seen at
      Southland Hospital from 1997 to 2001. Of a total of 62 cases of salmonellosis, 30
      were culture-positive for S. Brandenburg (48%). Of these cases, 13 (43%) were
      from extra-intestinal sites. Eleven of these 13 (85%) cases did not have any risk
      factors for invasive disease. During the study period, the incidence of S.
      Brandenburg infection increased, as did the incidence of invasive disease.
      CONCLUSION: The incidence and invasive potential of S. Brandenburg seems to be
      increasing, particularly in Southland, with peak infection rates corresponding to
      the lambing and calving season (September to November). S. Brandenburg seen in
      immunocompetent hosts may be a more invasive organism, and present with a wider
      spectrum of disease than has been previously considered.

PMID- 15570329
TI  - The Orewa Speech: another threat to Maori health?
AB  - In early 2004, Dr Don Brash, leader of the National Party (New Zealand's
      opposition political party), gave a speech to a community group regarding what he
      perceived to be the preferential treatment of Maori in health and education
      policies. This viewpoint article is written by a group of concerned medical
      students at Otago University. It argues that epidemiological data provide strong
      support for specifically addressing Maori health need, whilst the Treaty of
      Waitangi represents a contractual obligation on behalf of the New Zealand
      Government to ensure equity of outcome for Maori. Underpinning both the
      epidemiological and legal arguments, are ethical principles. The central tenets
      of medicine (ie, to reduce suffering, and to improve and prolong the quality and
      length of life) should provide a strong driving force to address these
      inequalities.

PMID- 15570330
TI  - Lifestyle screening: development of an acceptable multi-item general practice
      tool.
AB  - AIMS: To develop a short screening tool for lifestyle and mental-health risk
      factors that adults can self-administer, and to determine acceptability and
      feasibility of use of this tool in primary care settings. METHODS: The multi-item
      tool was designed to screen patients in rural and urban New Zealand general
      practices for smoking, alcohol and drug misuse, problem gambling, depression,
      anxiety, abuse, anger, sedentary lifestyle, and weight issues. Patients were
      offered help for identified risk factors. Fifty consecutive adult patients per
      practice (n=2,543) were recruited to participate from 20 randomly-selected urban
      general practitioners; 20 general practice nurses and 11 rural general
      practitioners. RESULTS: Patients came from diverse ethnic, geographical, and
      socioeconomic backgrounds. The sample prevalence of positive responses identified
      ranged from 2.8% (gambling) to 42.7% (depression). The number of patients
      requesting immediate assistance with these responses (0.5 to 13.5%) did not
      overwhelm clinicians. The tool was well accepted by patients, with few objections
      to specific questions (0.1-0.8%). Most practitioners stated they will use the
      screening tool once available. CONCLUSIONS: Screening for lifestyle and mental
      health risk factors is becoming increasingly important in primary health care.
      This screening tool was acceptable to patients and was not considered overly
      burdensome by practitioners.

PMID- 15570331
TI  - The health of alternative education students compared to secondary school
      students: a New Zealand study.
AB  - AIM: To describe the health and wellbeing of alternative education (AE) students
      from the Northland and Auckland regions of New Zealand and compare these AE
      students with secondary school students of similar age from the same region.
      METHODS: All 36 AE schools in the region were surveyed in the year 2000. A total
      of 268 AE students completed a youth health questionnaire using laptop computers.
      Regional data from a 2001 national secondary school survey that used the same
      methodology was used for comparison with the AE student data. RESULTS: This study
      found that compared to secondary school students, AE students are more likely to
      come from disadvantaged backgrounds, with proportionally more AE students
      reporting socioeconomic difficulty and less parental connection. AE students were
      more likely to be vulnerable to behaviours that endanger their health, such as
      drug and alcohol use, risky sexual behaviours and risky motor vehicle use than
      secondary school students. AE students were also more likely to suffer from high
      levels of depressive symptoms indicative of significant psychopathology.
      CONCLUSIONS: Findings from this study support the need for specific policies and
      programs for alternative secondary school students to address urgent and serious
      threats to their health and wellbeing.

PMID- 15570332
TI  - A descriptive epidemiology of giardiasis in New Zealand and gaps in surveillance
      data.
AB  - INTRODUCTION: Giardia is the most commonly notified waterborne disease in New
      Zealand, which has high incidence rates compared with other developed countries.
      Four years of giardiasis notification data were analysed to describe the
      epidemiological patterns of infection in New Zealand and compared with local and
      international data. METHODS: Anonymised information was collected nationally for
      7818 notified cases of giardiasis between July 1996 and June 2000. International
      data were collected from the data sources of respective countries. Infection
      rates adjusted for confounding factors were calculated and presented by age,
      gender, ethnicity, and area using statistical and spatial methods. RESULTS: Most
      cases occurred in the 1-4 year age group followed by the 25-44 year age group,
      and were of Pakeha/European ethnicity. Ethnicity was unknown for 18% of cases,
      thus affecting demographic calculations. Rates were elevated for several Health
      Districts in New Zealand (West Coast, Wellington, Waikato, Auckland, Hawke's Bay,
      Hutt, Rotorua, and Tauranga). CONCLUSIONS: The higher rates of giardiasis
      observed in New Zealand, in comparison with other developed countries, may be
      related to environmental or social factors. Time-trend analysis suggests a
      seasonal pattern. This study identified vulnerable groups and major data-gaps.
      Recommendations for improvements in disease surveillance and data quality are
      discussed. Geographical information system (GIS) applications are useful for
      disease monitoring.

PMID- 15570333
TI  - Effects of nursing industrial action on relatives of Intensive Care Unit
      patients: a 16-month follow-up.
AB  - AIMS: In December 2001, nursing industrial action occurred at Christchurch
      Hospital. This study assesses the effect industrial action had on relatives of
      those Intensive Care Unit (ICU) patients involved. METHOD: A written
      questionnaire was sent to the relatives of the 17 patients on Intensive Care
      around the time of the strike; 11 of these patients had needed to be transferred
      to out of region hospitals for continuing care, whilst the others remained in the
      intensive care unit. Comparisons were made with a control group of 26 next-of
      kin. RESULTS: Compared with relatives of patients not involved in the strike,
      relatives involved during the strike were significantly more angry (p<0.007) and
      less trusting that the patients had received the best possible care (p<0.05).
      Compared to the control group, they were also more negative in their continuing
      view of the healthcare system (p<0.05). Those relatives involved in air transfers
      were more distressed (p<0.05), angry (p<0.001), and less trusting than those not
      involved in a transfer (p<0.005). CONCLUSION: The study shows that industrial
      action caused measurable distress and anxiety to the relatives involved some 16
      months after the strike, especially in patients who were transferred. A
      persistent negative perception of the healthcare system in New Zealand could be
      demonstrated in this group.

PMID- 15570334
TI  - Small bowel bleeding as a unique presentation of metastatic lung carcinoma.

PMID- 15570335
TI  - The Auckland Hospital Ethics Committee: the first 7 years.
AB  - We describe the establishment and development of the Clinical Ethics Advisory
      Group (CEAG) at Auckland Hospital. The CEAG provides a case-consultation service
      for clinicians and managers and on request advises on policies and guidelines.
      Relatively few cases have been referred for consultation despite the fact that
      82% of doctors and 98% of nurses see a role for the CEAG in helping to resolve
      dilemmas in clinical practice. Most clinicians (80%) who have consulted the CEAG
      have valued the opinions they were given. The majority of doctors (81%) and
      nurses (76%) indicated that they would value further education in ethics. Based
      on our experience and a review of the literature, we recommend that all
      healthcare workers should have access to ethical expertise.

PMID- 15570336
TI  - Mortality, morbidity, and asbestosis in New Zealand: the hidden legacy of
      asbestos exposure.
AB  - AIMS: To examine the morbidity and mortality patterns of patients with asbestosis
      in New Zealand to determine (more fully) the overall health impact of past
      exposure to asbestos. METHODS: Individual mortality, cancer and hospital records
      for all New Zealand men diagnosed with asbestosis between 1974-2001 were
      examined. Mortality data were analysed for time trends, cause of death, and
      occupation. Trends for patients diagnosed with asbestosis were compared with
      those diagnosed with lung cancer. Hospital discharge data for men with asbestosis
      were examined to determine reasons for hospitalisation, resource utility, and
      recent hospitalisation trends. RESULTS: Death rates for New Zealand males dying
      with asbestosis increased between 1974-1999. Only 17% of deaths of males dying
      with asbestosis were directly attributed to this cause; the remainder were
      attributed to other non-malignant and malignant respiratory disease. Deaths from
      asbestos-related lung disease were grossly underestimated. Death certificates of
      men dying with asbestosis were found in all major occupational groups. Trends in
      hospital discharges may provide additional information for the overall modelling
      of the current epidemic of asbestos related disease. CONCLUSION: The number of
      men dying with asbestosis in NZ has increased in line with mesothelioma. There is
      some indication that asbestosis prevalence may have peaked for the most serious
      cases of asbestosis. Some level of asbestos exposure, as indicated by asbestosis,
      may be present in all major occupational groups.

PMID- 15570337
TI  - Shaken baby syndrome: a medicolegal problem.

PMID- 15570338
TI  - Obstetric perspectives: quality within choice.

PMID- 15570339
TI  - New Zealand's cervical cytology history: implications for the control of cervical
      cancer.

PMID- 15570340
TI  - Smoking among mothers of a Pacific Island birth cohort in New Zealand: associated
      factors.
AB  - AIMS: The present study investigated (among mothers of a Pacific Island birth
      cohort) the rates of smoking before, during, and after pregnancy as well as
      factors predictive of smoking during pregnancy. METHODS: Data were gathered as
      part of the Pacific Islands Families (PIF) Study. In this study, mothers of a
      cohort of 1398 Pacific infants born in Middlemore Hospital, Auckland during 2000
      were interviewed when their infants were 6 weeks old. Mothers were questioned
      about their maternal health, and lifestyle behaviours such as cigarette smoking.
      Additional data were obtained from hospital records. Analyses focused on 1365
      biological mothers. RESULTS: Overall, 339 (approximately one-quarter) of the
      mothers reported smoking during pregnancy. 331 (76.1%) of the 435 smokers (before
      pregnancy) continued to smoke during pregnancy, and eight mothers commenced
      smoking once pregnant. Smoking rates for each trimester were 23.7% in the first,
      21.0% in the second, and 20.4% in the third trimester of pregnancy, respectively.
      Multivariate analyses showed that smoking was significantly associated with
      several factors, including indicators of disadvantage and degree of
      westernisation. CONCLUSIONS: Greater efforts are needed to reduce smoking during
      pregnancy among Pacific women. Findings can be used to inform public health
      policy and smoking cessation programmes for Pacific families.

PMID- 15570341
TI  - Socioeconomic deprivation and the incidence of cervical cancer in New Zealand:
      1988-1998.
AB  - AIM: This study aims to identify the relationship between socioeconomic
      deprivation and cervical cancer incidence in New Zealand. METHOD: A 10-year
      cohort of cervical cancer cases was identified from the population-based New
      Zealand Cancer Registry. The New Zealand Deprivation Index (NZDep96) is a
      validated census-based measure of material and social deprivation in
      geographically defined small-population groups. Incidence rates of cervical
      cancer were correlated with socioeconomic deprivation. RESULTS: There were 2629
      new registrations of cervical cancer from 1988 to 1998. A positive association
      was found between socioeconomic deprivation and incidence rates of cervical
      cancer. Women living in the most socially and materially deprived areas of New
      Zealand were more than twice as likely to develop cervical cancer than women
      living in socially and materially advantaged areas. CONCLUSION: Greater
      socioeconomic deprivation is associated with an increased incidence of cervical
      cancer in New Zealand. The link between socioeconomic deprivation and cervical
      cancer incidence is likely to be complex. The identification of modifiable
      factors in cervical screening uptake in areas of socioeconomic deprivation should
      be a research priority.

PMID- 15570342
TI  - Violence against women in New Zealand: prevalence and health consequences.
AB  - BACKGROUND: This study reports on a large cross-sectional study of violence
      against women in New Zealand, and outlines the health consequences associated
      with intimate partner violence (IPV). METHODS: The study population was women
      aged 18-64 years in Auckland and north Waikato. A population-based cluster
      sampling scheme was used, with face-to-face interviews with one randomly selected
      woman from each household. Analyses included calculation of prevalence rates and
      logistic regression models to determine associations. RESULTS: The overall
      response rate was 66.9%, n=2,855. Fifteen percent of participants in Auckland and
      17% in the north Waikato reported at least one act of physical violence inflicted
      by non-partners in their lifetime. Sexual violence by non-partners was reported
      by 9% and 12% of women in Auckland and Waikato respectively. Among ever-partnered
      women, 33% in Auckland and 39% in Waikato had experienced at least one act of
      physical and/or sexual violence by an intimate partner. Victims of IPV were two
      times more likely to have visited a healthcare provider in the previous 4 weeks.
      IPV was significantly associated with current health effects, including: self
      perceived poor health, physical health problems (eg, pain), and mental health
      problems (eg, suicide attempts). CONCLUSION: The high prevalence of violence and
      its pervasive association with a wide range of physical and mental health effects
      suggest that it warrants consideration as a significant factor underpinning ill
      health in women. Prevention efforts must concentrate not only on reducing the
      perpetration of violence against women, in particular IPV, but also on developing
      and sustaining appropriate responses to victims of violence within the health
      system.

PMID- 15570343
TI  - Prevalence of intimate partner violence among women presenting to an urban adult
      and paediatric emergency care department.
AB  - AIM: To determine the prevalence of intimate partner violence among women seeking
      emergency healthcare. METHODS: Trained research assistants asked eligible adult
      women presenting to an urban emergency care department during randomly selected 4
      hour time blocks to participate in a study about violence between partners. A
      structured interview was conducted that included a partner violence screen,
      identification of high risk, and lifetime prevalence. Culturally safe study
      protocols were developed that held women's and children's safety paramount.
      RESULTS: 174 women aged 16 to 88 years of age participated. Overall, 21% (95%
      CI=15.2%, 27.4%) of women screened positive for partner violence, and 44% (95%
      CI=36.9%, 51.7%) reported partner violence at some time in their adulthood.
      CONCLUSION: A large proportion of women were willing to answer sensitive
      questions regarding partner violence during an emergency visit. Rates of partner
      violence among women seeking healthcare were significant, and consistent with
      rates reported internationally. Healthcare providers have an opportunity to
      identify and intervene to assist women exposed to abuse by a partner.

PMID- 15570344
TI  - Changes in the use of Hormone Replacement Therapy in New Zealand following the
      publication of the Women's Health Initiative trial.
AB  - BACKGROUND: Results of the Women's Health Initiative (WHI) trial on Hormone
      Replacement Therapy (HRT) have recently been published. We carried out a national
      survey to assess the impact of the July 2002 findings on HRT use. We also studied
      where women obtained information, as well as their opinions and beliefs. METHODS:
      500 women aged 45 to 64 years were randomly selected from the electoral rolls,
      and were sent a questionnaire regarding use and knowledge of HRT. There was phone
      follow-up for those who did not reply. Variables were tested for associations
      using the Chi-squared test and adjusted for confounding. RESULTS: We received 298
      questionnaires back, and a further 20 responses were received by phone (response
      rate 66%). We found that 15% of women were taking HRT during June 2002 compared
      to 11% taking HRT in December 2002, a drop of 36%. Even in July 2002, only 2% of
      users reported taking it to prevent coronary heart disease. Findings from the WHI
      trial were the main reason for stopping HRT. Women expressed an interest in more
      'natural' therapies over HRT. Most women had heard information on HRT, however
      knowledge was lacking in some areas. CONCLUSIONS: The publicity following
      publication of the WHI trial has led to a decline in HRT use in New Zealand
      consistent with national sales data. Nevertheless, most women were not using HRT
      for heart disease prevention even before the WHI trial was published, suggesting
      that the NZ Guidelines Group 2001 recommendation against such use had been widely
      acted on. Women have expressed an interest in alternative therapies and more
      research is required in these areas. Methods of stopping HRT are understudied.

PMID- 15570345
TI  - Specific oral contraceptive use and venous thromboembolism resulting in hospital
      admission.
AB  - OBJECTIVE: To determine whether there is an increased risk of venous
      thromboembolism (VTE) with anti-androgen oral contraceptives containing
      cyproterone acetate and ethinyloestradiol. METHODS: Comparison of the frequency
      of specific oral contraceptive use in patients aged 15 to 55 years discharged
      from hospital with radiologically confirmed deep vein thrombosis (DVT) and/or
      pulmonary embolism (PE) with the expected frequency of use derived from national
      prescription data. MAIN OUTCOME MEASURE: Ratio of observed frequency of specific
      oral contraceptive use in patients with VTE versus expected frequency of use.
      RESULTS: The rank order for observed versus expected use was anti-androgen >
      third-generation, > second-generation, > progestogen-only oral contraceptive
      agents with ratios of 1.93, 1.36, 0.70, and 0.39, respectively. CONCLUSION: The
      risk of VTE resulting in hospital admission associated with anti-androgen oral
      contraceptive use is at least as high as with third generation use.

PMID- 15570346
TI  - Obstetric regional analgesia services in New Zealand: a national survey.
AB  - AIMS: To investigate the availability and pattern of obstetric regional analgesia
      services in New Zealand. METHODS: A postal survey of all registered obstetric
      facilities in New Zealand for year 2000 was carried out. RESULTS: A total of 87
      obstetric facilities were identified. Sixty-two percent of them responded to our
      survey, which covered 75% of all deliveries in year 2000. Numerous non
      pharmacological and systemic analgesia modalities were widely available.
      Obstetric regional analgesia services were available in 20 facilities (38%),
      which provided obstetric care for 92.5% of all deliveries identified in this
      survey. Only the number of deliveries per year in a facility was associated with
      the availability of obstetric regional analgesia services (OR: 1.03; 95% CI: 1.01
      1.06; p=0.03), not the location of the facility, whether in non-major urban or
      major urban areas. Among all the obstetric regional analgesia techniques that
      were available, patient controlled epidural analgesia (PCEA) was not widely used
      at the time of this survey. CONCLUSIONS: Availability of obstetric regional
      analgesia services in New Zealand is very geographically focused, and appears to
      match closely with the distribution of obstetric deliveries in New Zealand.

PMID- 15570347
TI  - Genetic testing in New Zealand: the role of the general practitioner.
AB  - AIM: The aim of the study commissioned by the National Health Committee (NHC) was
      to explore the current practice and training needs of general practitioners (GPs)
      in relation to genetic testing in New Zealand, and to gauge GPs' perceptions of
      access to genetic services for their patients. METHOD: A postal survey was sent
      to a national, random sample of 600 GPs. Responses were received from 328 (56%)
      of the 586 eligible GPs. RESULTS: Most GPs felt they lacked experience and
      knowledge of genetic testing, had received little formal training, and many were
      unsure of how to contact genetic services locally. GPs recognised the importance
      of their role in genetic testing and requested further information. CONCLUSIONS:
      GPs in New Zealand have an increasingly important role to play in genetic
      testing. The nature of this role in the new genetics era needs to be carefully
      considered as will the best way to implement any future educational strategies.

PMID- 15570348
TI  - The development of cervical cytology and colposcopy in New Zealand: 50 years
      since the first cytology screening laboratory at National Women's Hospital.

PMID- 15570349
TI  - Maternal methamphetamine use during pregnancy and child outcome: what do we know?

PMID- 15570350
TI  - An intrapartum giant cervical polyp.

PMID- 15570351
TI  - Arteriovenous malformations of the uterus.
AB  - Uterine arteriovenous malformations are rare lesions with a considerable risk
      potential. Clinical presentation varies from no signs over various degree of
      menorrhagia to massive life-threatening vaginal bleeding. Clinical suspicion is
      essential for a prompt diagnosis and treatment. Three cases of uterine
      arteriovenous malformations are presented. These cases were managed either
      expectantly with 100% resolution or surgically by hysterectomy. This report
      stresses the importance of site and size of these arteriovenous malformations in
      considering the treatment modalities.

PMID- 15570352
TI  - Universal Newborn Hearing Screening introduced to NICU infants in Canterbury
      Province, New Zealand.
AB  - AIMS: Universal Newborn Hearing Screening (UNHS) is being implemented worldwide
      as an effective method of early identification of hearing loss. The impact of
      delayed detection of sensorineural hearing loss is a major lifelong impairment.
      The aim of the study was to assess the feasibility of introducing universal
      newborn hearing screening over the 12-month period in the Neonatal Intensive Care
      Unit (NICU) at Christchurch Women's Hospital, and to assess the costs, and
      resources required. METHODS: Universal Newborn Hearing Screening was conducted
      over a 12 month period in the Neonatal Service of Christchurch Women's Hospital.
      Throughout the implementation period, data were collected to monitor and
      benchmark against World's best practice. RESULTS: During the 12 months of the
      study, 435 babies were screened for hearing loss in the Neonatal Service at
      Christchurch Women's Hospital. Of these babies, 19 (4.37%) were referred for
      diagnostic 'auditory brainstem response' ABR testing to confirm hearing loss. Two
      babies were confirmed with hearing loss, with only one baby exhibiting a known
      risk factor for deafness. This resulted in a positive predictive index of 10.53%.
      CONCLUSIONS: This study highlights that UNHS can be implemented efficiently and
      cost-effectively within the Neonatal Service of a New Zealand Hospital. The
      results were consistent with best practice, and show the benefits of UNHS against
      'at risk' screening. The ultimate success of this study will be in the
      implementation of UNHS across New Zealand.

PMID- 15570353
TI  - Caesarean section in term nulliparous women at Wellington Hospital in 2001: a
      regional audit.
AB  - AIMS: The aims of this audit were to determine the frequency of caesarean section
      (CS) in the Wellington region for term nulliparous women, to evaluate the local
      demographic and clinical factors associated with CS, and to assess the quality of
      clinical care. METHODS: Nulliparous women with singleton live pregnancies and a
      gestational age greater than and equal to 36 weeks who had a CS in Wellington
      Hospital during 1 January 2001 to 30 June 2001 were identified using a
      computerised database. The Hospital records were reviewed. Demographic and
      clinical factors associated with CS were analysed and assessed against standards
      from the literature. RESULTS: A total of 743 women with a singleton live
      pregnancy greater than and equal to 36 weeks delivered during the period. 209
      women met the criteria and 201 files were available. The estimated corrected CS
      rate was 27%. Thirty-six women (5%, 36/743) had an elective CS, and 165 (22%,
      165/743) had an emergency CS. Dystocia (48%), suspected fetal compromise (23%),
      and malpresentation (20%) represented the most common indications for CS. A
      significant proportion of CS were performed without meeting the standards.
      CONCLUSIONS: In term nulliparous women, the indications for CS and the compliance
      with recognised standards from the literature were very similar to those observed
      in other industrialised countries.

PMID- 15570354
TI  - Medical image. Cystolithic lithuresis.

PMID- 15570355
TI  - Regarding 'Resident Medical Officer working conditions in New Zealand: results of
      a recent survey'.

PMID- 15570356
TI  - Regarding 'Participation in small-group learning'.

PMID- 15570357
TI  - A comparison of clinical outcomes between Canadian and American patients after
      nonurgent coronary stenting.
AB  - BACKGROUND: Practice patterns for percutaneous coronary interventions (PCIs) may
      differ between Canada and the United States. Few data are available comparing PCI
      outcomes between the two countries in the era of coronary stenting and adjunctive
      glycoprotein IIb/IIIa inhibition. METHODS: In the Enhanced Suppression of the
      Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, 2064 patients
      were randomly assigned to receive eptifibatide or placebo during nonurgent PCI.
      The 30-day and one-year rates of death, myocardial infarction (MI) and target
      vessel revascularization (TVR) were compared between Canadian and American
      patients enrolled in the ESPRIT trial. RESULTS: There were 1531 American patients
      and 533 Canadian patients enrolled. Americans were older and heavier, and had a
      higher incidence of cardiac risk factors than Canadians (P<0.05 for all
      variables). Canadian patients had a lower incidence of death, MI and TVR at 30
      days (6.2% versus 10.4%, P=0.004) and at one year (14.8% versus 21.5%, P=0.0006).
      After adjusting for known baseline differences, enrollment in Canada remained a
      significant predictor of reduced ischemic complications at 30 days (OR=0.53,
      c2=9.0, P=0.003). Similar results were observed at one year. Eptifibatide was
      superior to placebo in both groups of patients. CONCLUSIONS: This analysis is
      among the first to show Canadian patients to have fewer adverse events than
      American patients after nonurgent PCI. This effect was independent of known
      baseline differences between the patients in each country. The relative treatment
      effect of eptifibatide in Canadian patients paralleled that observed in the main
      ESPRIT trial and in American patients.

PMID- 15570359
TI  - Metals in perspective: introduction.

PMID- 15570360
TI  - Syntheses of 11C- and 18F-labeled carboxylic esters within a hydrodynamically
      driven micro-reactor.
AB  - Carboxylic esters were successfully labeled with one of two short-lived positron
      emitters, carbon-11 or fluorine-18, within a hydrodynamically-driven micro
      reactor. The non-radioactive methyl ester was obtained at room temperature; its
      yield increased with higher substrate concentration and with reduced infusion
      rate. Radioactive methyl ester was obtained from the reaction of (10 mM) with in
      56% decay-corrected radiochemical yield (RCY) at an infusion rate of 10 microL
      min(-1), and when the infusion rate was reduced to 1 microL min(-1), the RCY
      increased to 88%. The synthesis of the non-radioactive fluoroethyl ester from and
      required heating of the micro-reactor on a heating block at 80 degrees C (14-17%
      RCY), whilst the corresponding radioactive from and was obtained in 10% RCY. The
      radioactive 'peripheral' benzodiazepine receptor ligand was obtained from the
      reaction of acid with labeling agent in 45% RCY at an infusion rate of 10 microL
      min(-1). When the infusion rate was reduced to 1 microL min(-1), the RCY
      increased to 65%. The results exemplify a new methodology for producing
      radiotracers for imaging with positron emission tomography that has many
      potential advantages, including a requirement for small quantities of substrates,
      enhanced reaction, rapid reaction optimisation and easy product purification.

PMID- 15570361
TI  - Macro-to-micro interfaces for microfluidic devices.
AB  - Since the concept of miniaturized total analysis systems (microTAS) was invented,
      a great number of microfluidic devices have been demonstrated for a variety of
      applications. However, an important hurdle that still needs to be cleared is the
      connection of a microfluidic device with the rest of the world, which is often
      referred to as the macro-to-micro interface, interconnect, or world-to-chip
      interface. In this review, we will examine the methods used by pioneers in the
      field and other investigators, review the approaches for capillary
      electrophoresis-based devices and those using pneumatic pumping, and present
      additional discussion on interface standardization and choosing and designing
      interconnects for your applications.

PMID- 15570362
TI  - Miniaturised nucleic acid analysis.
AB  - The application of micro total analysis systems has grown exponentially over the
      past few years, particularly diversifying in disciplines related to bioassays.
      The primary focus of this review is to detail recent new approaches to sample
      preparation, nucleic acid amplification and detection within microfluidic devices
      or at the microscale level. We also introduce some applications that have as yet
      to be explored in a miniaturised environment, but should benefit from
      improvements in analytical efficiency and functionality when transferred to
      planar-chip formats. The studies described in this review were published in
      commonly available journals as well as in the proceedings of three major
      conferences relevant to microfluidics (Micro Total Analysis Systems, Transducers
      and The Nanotechnology Conference and Trade Show). Although an emphasis has been
      placed on papers published since 2002, pertinent articles preceding this
      publication year have also been included.

PMID- 15570363
TI  - In-situ quantitative analysis of a prostate-specific antigen (PSA) using a
      nanomechanical PZT cantilever.
AB  - We report on a novel technique of resonant frequency shift measurement based on a
      nanomechanical cantilever with a PZT actuating layer for label-free detection of
      a prostate-specific antigen (PSA) in a liquid environment. The nanomechanical PZT
      thin film cantilever is composed of SiO(2)/Ta/Pt/PZT/Pt/SiO(2) on a SiN(x)
      supporting layer for simultaneous self-exciting and sensing; it was fabricated
      using a standard MEMS (micro electromechanical system) process. The specific
      binding characteristics of the PSA antigen to its antibody, which is immobilized
      with Calixcrown self-assembled monolayers (SAMs) on a gold surface deposited on a
      cantilever, are determined to a high sensitivity. For the bioassay in a liquid
      environment, a liquid test cell with a 20 microl volume reaction chamber has been
      fabricated, using a bonding technique between poly(dimethyl siloxane) (PDMS)
      bilayers. An observed trend of resonant frequency change with respect to time
      could be explained by the binding kinetics due to the Langmuir isotherm and
      diffusion and by the effects of a small volume reaction chamber. In the saturated
      regimes, the resonant frequency of the cantilever increased with increase of the
      PSA concentration in the reaction chamber, showing that the trend of the
      resonance frequency change was similar to that of the fluorescence results. The
      saturated resonance frequency shift of the cantilever was proportional to the PSA
      antigen concentration of analyte solution.

PMID- 15570364
TI  - Automated, controlled deposition of nanoparticles on polyelectrolyte-coated
      silicon from chemomechanically patterned droplet arrays.
AB  - This paper describes three advances in lab on a chip technology. First, it is
      shown that chemomechanical surface patterning can be performed using a
      commercially available liquid handler that has undergone only minor
      modifications. These capabilities are demonstrated by making and then
      characterizing smaller hydrophobic corrals, made with a diamond tip, than have
      previously been reported. Hydrophobic corrals are small enclosures on a surface
      that are ringed by hydrophobic lines. They hold droplets of high surface tension
      solutions. They allow a surface to be subdivided into individually addressable
      elements, thus providing a platform for conducting many simultaneous surface
      experiments with small (down to ca. 1 microL) liquid volumes. An important
      consequence of this work is that it makes chemomechanical surface patterning,
      which is a valuable and straightforward method for surface modification, much
      more accessible to the technical community. Second, it is shown that an entire
      array of hydrophobic corrals can be simultaneously coated with polyelectrolyte
      multilayers, but that the hydrophobic corrals still retain the ability to hold
      liquids after this deposition. The robotic arm of the liquid handler is again
      employed to manufacture this ultrathin film. Finally, as a demonstration of the
      capability of this technology to create complex patterned arrays on surfaces from
      solution for biological or nanostructured materials applications, and again
      employing the liquid handler, polyelectrolyte-coated hydrophobic corrals are
      individually addressed and loaded with a solution containing gold nanoparticles
      for independently specified times. The density and morphology of deposited
      nanoparticle monolayers were studied by scanning electron microscopy. The
      deposition of gold nanoparticles onto a chip occurred at a constant rate (0.5%
      min(-1)) over the range of times studied.

PMID- 15570365
TI  - Electroosmotic mixing in microchannels.
AB  - Mixing is an essential, yet challenging, process step for many Lab on a Chip
      (LOC) applications. This paper presents a method of mixing for microfluidic
      devices that relies upon electroosmotic flow. In physical tests and in computer
      simulations, we periodically vary the electric field with time to mix two aqueous
      solutions. Good mixing is shown to occur when the electroosmotic flow at the two
      inlets pulse out of phase, the Strouhal number is on the order of 1, and the
      pulse volumes are on the order of the intersection volume.

PMID- 15570366
TI  - High-sensitivity miniaturized immunoassays for tumor necrosis factor alpha using
      microfluidic systems.
AB  - We use microfluidic chips to detect the biologically important cytokine tumor
      necrosis factor alpha (TNF- alpha) with picomolar sensitivity using sub
      microliter volumes of samples and reagents. The chips comprise a number of
      independent capillary systems (CSs), each of which is composed of a filling port,
      an appended microchannel, and a capillary pump. Each CS fills spontaneously by
      capillary forces and includes a self-regulating mechanism that prevents
      adventitious drainage of the microchannels. Thus, interactive control of the flow
      in each CS is easily achieved via collective control of the evaporation in all
      CSs by means of two Peltier elements that can independently heat and cool. Long
      incubation times are crucial for high sensitivity assays and can be conveniently
      obtained by adjusting the evaporation rate to have low flow rates of
      approximately 30 nL min(-1). The assay is a sandwich fluorescence immunoassay and
      takes place on the surface of a poly(dimethylsiloxane)(PDMS) slab placed across
      the microchannels. We precoat PDMS with capture antibodies (Abs), localize the
      capture of analyte molecules using a chip, then bind the captured analyte
      molecules with fluorescently-tagged detection Abs using a second chip. The assay
      results in a mosaic of fluorescence signals on the PDMS surface which are
      measured using a fluorescence scanner. We show that PDMS is a compatible material
      for high sensitivity fluorescence assays, provided that detection antibodies with
      long excitation wavelength fluorophores ( > or =580 nm) are employed. The chip
      design, long incubation times, proper choice of fluorophores, and optimization of
      the detection Ab concentration all combine to achieve high-sensitivity assays.
      This is exemplified by an experiment with 170 assay sites, occupying an area of
      approximately 0.6 mm(2) on PDMS to detect TNF-alpha in 600 nL of a dendritic cell
      (DC) culture medium with a sensitivity of approximately 20 pg mL(-1)(1.14 pM).

PMID- 15570367
TI  - Microchip-based enzyme-linked immunosorbent assay (microELISA) system with
      thermal lens detection.
AB  - A microchip-based enzyme-linked immunosorbent assay (microELISA) system was
      developed and interferon-gamma was successfully determined. The system was
      composed of a microchip with a Y-shaped microchannel and a dam structure,
      polystyrene microbeads, and a thermal lens microscope (TLM). All reactions
      required for the immunoassay were done in the microchannel by successive
      introduction of a sample and regents. The enzyme reaction product, in a liquid
      phase, was detected downstream in the channel using the TLM as substrate solution
      was injected. The antigen-antibody reaction time was shortened by the microchip
      integration. The limit of the determination was improved by adopting the enzyme
      label. Moreover, detection procedures were greatly simplified and required time
      for the detection was significantly cut. The system has good potential to be
      developed as a small and automated high throughput analyzer.

PMID- 15570368
TI  - Hydrodynamic microfabrication via"on the fly" photopolymerization of microscale
      fibers and tubes.
AB  - A microfluidic apparatus capable of creating continuous microscale cylindrical
      polymeric structures has been developed. This system is able to produce
      microstructures (e.g. fibers, tubes) by employing 3D multiple stream laminar flow
      and "on the fly"in-situ photopolymerization. The details of the fabrication
      process and the characterization of the produced microfibers are described. The
      apparatus is constructed by merging pulled glass pipettes with PDMS molding
      technology and used to manufacture the fibers and tubes. By controlling the
      sample and sheath volume flow rates, the dimensions of the microstructures
      produced can be altered without re-tooling. The fiber properties including
      elasticity, stimuli responsiveness, and biosensing are characterized. Responsive
      woven fabric and biosensing fibers are demonstrated. The fabrication process is
      simple, cost effective and flexible in materials, geometries, and scales.

PMID- 15570369
TI  - A new dynamic electrochemical transduction mechanism for interdigitated array
      microelectrodes.
AB  - A dynamic electrochemical transduction mechanism for interdigitated array
      microelectrodes using an electrical charge pumping method is presented in this
      paper. In this dynamic transduction mechanism, a charged external capacitor is
      used as the charge supplier for the electrochemical reaction of the reversible
      redox species at the interdigitated array electrodes. The charges stored in the
      capacitor are consumed as the electrochemical reaction current, which causes the
      capacitor potential decay. The theoretical analysis has shown that the species
      concentration has a decisive effect on the capacitor potential decay, and
      therefore the characteristics of the capacitor potential decay are recorded and
      analyzed to evaluate the concentration of redox species. The new transduction
      mechanism has the advantages of achieving high sensitivity with small sensor area
      and simplifying the measurement instrumentation. As a demonstration device,
      interdigitated array microelectrodes (approximately 0.2 mm(2) electrode surface
      area) have been fabricated and successfully characterized using p-aminophenol as
      the redox species under this dynamic mechanism. The detection limit of p
      aminophenol was calculated to be approximately 4 x 10(-7) M for the sensor with
      the new dynamic transduction mechanism.

PMID- 15570370
TI  - Microfluidic enzymatic-reactors for peptide mapping: strategy, characterization,
      and performance.
AB  - The design and characterization of two kinds of poly(dimethylsiloxane)(PDMS)
      microfluidic enzymatic-reactors along with their analytical utility coupled to
      MALDI TOF and ESI MS were reported. Microfluidic devices integrated with
      microchannel and stainless steel tubing (SST) was fabricated using a PDMS casting
      technique, and was used for the preparation of the enzymatic-reactor. The
      chemical modification was performed by introducing carboxyl groups to PDMS
      surface based on ultraviolet graft polymerization of acrylic acid. The covalent
      and physical immobilization of trypsin was carried out with the use of the
      activation reagents 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide(EDC)/N
      hydroxysuccinimide (NHS) and a coupling reagent poly(diallyldimethylammonium
      chloride)(PDDA), respectively. The properties and success of processes of trypsin
      immobilization were investigated by measuring contact angle, infrared absorption
      by attenuated total reflection spectra, AFM imaging and electropherograms. An
      innovative feature of the microfluidic enzymatic-reactors is the feasibility of
      performing on-line protein analysis by embedded SST electrode and replaceable
      tip. The lab-made devices provide an excellent extent of digestion of several
      model proteins even at the fast flow rate of 3.5 microL min(-1) for the EDC/NHS
      made device and 0.8 microL min(-1) for the PDDA-made device, which afford very
      short residence times of 5 s and 20 s, respectively. In addition, the lab-made
      devices are less susceptive to memory effect and can be used for at least 50 runs
      in one week without noticeable loss of activity. Moreover, the degraded PDDA-made
      device can be regenerated by simple treatment of a HCl solution. These features
      are the most required for microfluidic devices used for protein analysis.

PMID- 15570371
TI  - Magnetically-driven biomimetic micro pumping using vortices.
AB  - Planar micropumps utilizing vortices shed by an oscillating ferromagnetic bar are
      presented. The movement of the bar is induced by magnetic coupling with an
      external spinning magnet. Thus, energy transfer is achieved without physical
      contact or need of any on-chip power source. To create vortices inside the chip,
      the Reynolds number is locally increased with the oscillation of the bar. The
      utilization of the vortices as a tool for efficient transfer of energy is
      inspired by the behaviour of swimming animals and flying insects in nature. The
      pumps operate in two different scales (milli-scale and micro-scale) in order to
      take advantage of both. Experiments are presented characterizing the pumps and
      their flow patterns. The range of operation of the pumps is from 3 microl min(-1)
      to 600 microl min(-1), though smaller flow rates are also possible.

PMID- 15570372
TI  - A microfluidic device based on gravity and electric force driving for flow
      cytometry and fluorescence activated cell sorting.
AB  - A novel method based on gravity and electric force driving of cells was developed
      for flow cytometry and fluorescence activated cell sorting in a microfluidic chip
      system. In the experiments cells flowed spontaneously under their own gravity in
      a upright microchip, passed through the detection region and then entered into
      the sorting electric field one by one at an average velocity of 0.55 mm s(-1) and
      were fluorescence activated cell sorted (FACS) by a switch-off activation
      program. In order to study the dynamical and kinematic characteristics of single
      cells in gravity and electric field of microchannels a physical and numerical
      module based on Newton's Law of motion was established and optimized.
      Hydroxylpropylmethyl cellulose (HPMC) was used to minimize cell assembling,
      sedimentation and adsorption to microchannels. This system was applied to
      estimate the necrotic and apoptotic effects of ultraviolet (UV) light on HeLa
      cells by exposing them to UV radiation for 10, 20 or 40 min and the results
      showed that UV radiation induced membrane damage contributed to the apoptosis and
      necrosis of HeLa cells.

PMID- 15570373
TI  - Micro magnetic stir-bar mixer integrated with parylene microfluidic channels.
AB  - Previously, we reported a micro magnetic stir-bar mixer driven by an external
      rotating magnetic field and its rapid mixing performance in polydimethyl-siloxane
      (PDMS) channels. The PDMS piece with embedded fluid channels were manually
      aligned to a glass substrate and assembled. In this paper, we report the
      fabrication and testing results of a micro magnetic stir-bar monolithically
      integrated in parylene surface-micromachined channels with improved design
      features, including small tolerance of the stir-bar to channel wall (10 microm).
      Using of parylene based microchannels with improved design not only provides
      improved mixing, but also eliminates certain problems associated with PDMS-based
      channels. For example, porosity of PDMS causes evaporation and absorption of
      chemicals and thus channels made of PDMS are prone to cross-contamination. We
      have also demonstrated that the magnetic stir-bar can be used to pump liquid in
      micro channels.

PMID- 15570374
TI  - Immunomagnetic T cell capture from blood for PCR analysis using microfluidic
      systems.
AB  - A one-step immunomagnetic separation technique was performed on a microfluidic
      platform for the isolation of specific cells from blood samples. The cell
      isolation and purification studies targeted T cells, as a model for low abundance
      cells (about 1:10,000 cells), with more dilute cells as the ultimate goal. T
      cells were successfully separated on-chip from human blood and from reconstituted
      blood samples. Quantitative polymerase chain reaction analysis of the captured
      cells was used to characterize the efficiency of T cell capture in a variety of
      flow path designs. Employing many (4-8), 50 microm deep narrow channels, with the
      same overall cross section as a single, 3 mm wide channel, was much more
      effective in structuring dense enough magnetic bead beds to trap cells in a
      flowing stream. The use of 8-multiple bifurcated flow paths increased capture
      efficiencies from approximately 20 up to 37%, when compared to a straight 8-way
      split design, indicating the value of ensuring uniform flow distribution into
      each channel in a flow manifold for effective cell capture. Sample flow rates of
      up to 3 microL min(-1) were evaluated in these capture beds.

PMID- 15570375
TI  - An efficient method for the fabrication of temperature-sensitive hydrogel
      microactuators.
AB  - In this article a new method for the photolithographical deposition of
      temperature-sensitive hydrogels is presented. The method can be used in
      conjunction with standard 365 nm UV-photolithography to accurately dimension and
      position temperature-sensitive hydrogel microactuators in a highly parallel
      fashion. A number of characteristics of the hydrogels were investigated. These
      include: the photolithographical reproduction quality, the effect of the
      crosslinking density in the hydrogels on their swelling behavior, the swelling
      hysteresis behavior, the effect of dimensional constraints on the swelling of the
      hydrogels and the effect of copolymerization with an ionizable comonomer on the
      temperature behavior of the hydrogels. The method presents a considerable
      improvement in the microfabrication of temperature-sensitive hydrogel
      microactuators and has potential for the mass-fabrication of these interesting
      microactuators.

PMID- 15570376
TI  - A model for Joule heating-induced dispersion in microchip electrophoresis.
AB  - This paper presents an analytical and parameterized model for analyzing the
      effects of Joule heating on analyte dispersion in electrophoretic separation
      microchannels. We first obtain non-uniform temperature distributions in the
      channel resulting from Joule heating, and then determine variations in
      electrophoretic velocity, based on the fact that the analyte's electrophoretic
      mobility depends on the buffer viscosity and hence temperature. The convection
      diffusion equation is then formulated and solved in terms of spatial moments of
      the analyte concentration. The resulting model is validated by both numerical
      simulations and experimental data, and holds for all mass transfer regimes,
      including unsteady dispersion processes that commonly occur in microchip
      electrophoresis. This model, which is given in terms of analytical expressions
      and fully parameterized with channel dimensions and material properties, applies
      to dispersion of analyte bands of general initial shape in straight and constant
      radius-turn channels. As such, the model can be used to represent analyte
      dispersion in microchannels of more general shape, such as serpentine- or spiral
      shaped channels.

PMID- 15570377
TI  - Micro patterning of cell and protein non-adhesive plasma polymerized coatings for
      biochip applications.
AB  - Micro scale patterning of bioactive surfaces is desirable for numerous biochip
      applications. Polyethyleneoxide-like (PEO-like) coating with non-fouling
      functionality has been deposited using low frequency AC plasma polymerization.
      The non-fouling properties of the coating were tested with human cells (HeLa) and
      fluorescence labeled proteins (isothiocyanate-labeled bovine serum albumin, i.e.
      FITC-BSA). The PEO-like coatings were fabricated by plasma polymerization of 12
      crown-4 (ppCrown) with plasma polymerized hexene (ppHexene) as adhesion layer.
      The coatings were micro patterned using conventional cleanroom photolithography
      and lift-off. Single cell arrays showed sharp contrast in cell adhesion between
      the untreated glass surface and the ppCrown layer. Similarly, proteins adsorbed
      selectively to untreated glass but not to ppCrown. The simplicity of the lift-off
      technique and the sturdiness and versatility of the plasma-polymerized coatings,
      make this technology highly suitable for bio-MEMS and biochip applications, where
      patterned high contrast non-fouling surfaces are needed.

PMID- 15570378
TI  - Rapid PCR in a continuous flow device.
AB  - Continuous flow polymerase chain reaction (CFPCR) devices are compact reactors
      suitable for microfabrication and the rapid amplification of target DNAs. For a
      given reactor design, the amplification time can be reduced simply by increasing
      the flow velocity through the isothermal zones of the device; for flow velocities
      near the design value, the PCR cocktail reaches thermal equilibrium at each zone
      quickly, so that near ideal temperature profiles can be obtained. However, at
      high flow velocities there are penalties of an increased pressure drop and a
      reduced residence time in each temperature zone for the DNA/reagent mixture, that
      potentially affect amplification efficiency. This study was carried out to
      evaluate the thermal and biochemical effects of high flow velocities in a spiral,
      20 cycle CFPCR device. Finite element analysis (FEA) was used to determine the
      steady-state temperature distribution along the micro-channel and the temperature
      of the DNA/reagent mixture in each temperature zone as a function of linear
      velocity. The critical transition was between the denaturation (95 degrees C) and
      renaturation (55 degrees C-68 degrees C) zones; above 6 mm s(-1) the fluid in a
      passively-cooled channel could not be reduced to the desired temperature and the
      duration of the temperature transition between zones increased with increased
      velocity. The amplification performance of the CFPCR as a function of linear
      velocity was assessed using 500 and 997 base pair (bp) fragments from lambda-DNA.
      Amplifications at velocities ranging from 1 mm s(-1) to 20 mm s(-1) were
      investigated. The 500 bp fragment could be observed in a total reaction time of
      1.7 min (5.2 s cycle(-1)) and the 997 bp fragment could be detected in 3.2 min
      (9.7 s cycle(-1)). The longer amplification time required for detection of the
      997 bp fragment was due to the device being operated at its enzyme kinetic limit
      (i.e., Taq polymerase deoxynucleotide incorporation rate).

PMID- 15570379
TI  - Effect of exposure dose on the replication fidelity and profile of very high
      aspect ratio microchannels in SU-8.
AB  - We are interested in using SU-8 dense gratings with very high aspect ratio
      microchannels as the master mold for fabrication of child molds needed for
      replication. For such applications, the sidewall taper angle and mask replication
      fidelity of SU-8 are very important. Increasing the exposure time was
      experimentally observed to decrease the width of the microchannel and the
      sidewall angle of SU-8 bars. A new diffraction-refraction-reflection model was
      also developed. The calculated microchannel width and sidewall angle at high
      exposure dose agreed well with the experimentally observed values indicating that
      reflection at the silicon substrate was significant. The larger than calculated
      actual microchannel width for low exposure dose was shown to be due to leaching
      of unreacted SU-8 in the developer. Dense gratings of high aspect ratio SU-8 bars
      separated by high aspect ratio (19.1) microchannels were also demonstrated.

PMID- 15570380
TI  - Use of laminar flow patterning for miniaturised biochemical assays.
AB  - Laminar flow in microfluidic chambers was used to construct low (one dimensional)
      density arrays suitable for miniaturized biochemical assays. By varying the ratio
      of flows of two guiding streams flanking a sample stream, precise focusing and
      positioning of the latter was achieved, and reactive species carried in the
      sample stream were deposited on functionalized chip surfaces as discrete 50
      microm wide lanes. Using different model systems we have confirmed the method's
      suitability for qualitative screening and quantification tasks in receptor-ligand
      assays, recording biotin-streptavidin interactions, DNA-hybridization and DNA
      triplex formation. The system is simple, fast, reproducible, flexible, and has
      small sample requirements.

PMID- 15570381
TI  - Robust polymer microfluidic device fabrication via contact liquid
      photolithographic polymerization (CLiPP).
AB  - Microfluidic devices are commonly fabricated in silicon or glass using
      micromachining technology or elastomers using soft lithography methods; however,
      invariable bulk material properties, limited surface modification methods and
      difficulty in fabricating high aspect ratio devices prevent these materials from
      being utilized in numerous applications and/or lead to high fabrication costs.
      Contact Liquid Photolithographic Polymerization (CLiPP) was developed as an
      alternative microfabrication approach that uniquely exploits living radical
      photopolymerization chemistry to facilitate surface modification of device
      components, fabrication of high aspect ratio structures from many different
      materials with numerous covalently-adhered layers and facile construction of
      three-dimensional devices. This contribution describes CLiPP and demonstrates
      unique advantages of this new technology for microfabrication of polymeric
      microdevices. Specifically, the procedure for fabricating devices with CLiPP is
      presented, the living radical photopolymerization chemistry which enables this
      technology is described, and examples of devices made using CLiPP are shown.

PMID- 15570382
TI  - Design and evaluation of a Dean vortex-based micromixer.
AB  - A mixer, based on the Dean vortex, is fabricated and tested in an on-chip format.
      When fluid is directed around a curve under pressure driven flow, the high
      velocity streams in the center of the channel experience a greater centripetal
      force and so are deflected outward. This creates a pair of counter-rotating
      vortices moving fluid toward the inner wall at the top and bottom of the channel
      and toward the outer wall in the center. For the geometries studied, the vortices
      were first seen at Reynolds numbers between 1 and 10 and became stronger as the
      flow velocity is increased. Vortex formation was monitored in channels with
      depth/width ratios of 0.5, 1.0, and 2.0. The lowest aspect ratio strongly
      suppressed vortex formation. Increasing the aspect ratio above 1 appeared to
      provide improved mixing. This design has the advantages of easy fabrication and
      low surface area.

PMID- 15570383
TI  - Erythrocytes-the 'house elves' of photodynamic therapy.
AB  - Photodynamic therapy (PDT) and fluorescence diagnosis (FD) are being developed
      for a number of clinical applications. Since fluorophores and photosensitising
      drugs are usually given systemically their effect on blood elements are of
      significant importance. Photodynamic effects on erythrocytes occur naturally in
      patients with erythropoietic protoporphyria (EPP). Exposure to small fluences, as
      obtained by the erythrocytes when they pass capillaries in the skin, leads to
      transfer of the photosensitiser protoporphyrin IX (PP IX), from EPP erythrocytes
      to endothelial cells. Thus, the erythrocytes are partly protected while the
      endothelial cells suffer photodamage. During photodynamic therapy in vivo
      erythrocytes are regularly photosensitised. This side effect is partly intended
      but mostly unwanted, and a summary of this topic is given. Furthermore, the
      effect of UV-A on erythrocytes that is accompanied with the formation of
      bilirubin is reviewed. Erythrocytes serve as convenient model cells for
      experimental research. Such use of erythrocytes to screen new photosensitisers
      may be of limited value. A combination of photohaemolysis and haemoglobin
      oxygenation may become the basis for an assay for in vitro phototoxicity.
      Erythrocytes from birds are good model cells for exploration of physiological and
      molecular mechanisms involved in PDT. A potential mechanism of PDT induced
      behaviour resembling apoptosis in erythrocytes is provided.PDT for sterilisation
      of erythrocyte concentrates has a potential for medical use. Photodynamic effects
      on the erythrocytes themselves should be avoided. This is realised by choosing a
      virus-selective photosensitiser, low fluences and treatment of the concentrates
      with agents like dipyridamole and antioxidants. Future aspects of applications of
      photosensitisation of red blood cells are discussed.

PMID- 15570384
TI  - Formation of radical cations of aziridines generated by laser flash photolysis.
AB  - The radical cations of 1-butyl-trans-2,3-diphenyl aziridine (1), 1-butyl-2-phenyl
      aziridine (2), 1,2-diphenyl aziridine (3) and 1-(p-methoxyphenyl)-2-phenyl
      aziridine (4) were generated upon laser flash photolysis in aqueous and aqueous
      acetonitrile solutions by direct photoionisation as indicated by the broad
      absorption band of the solvated electron above 550 nm as well.

PMID- 15570385
TI  - Photodynamic activity of cationic and non-charged Zn(II)
      tetrapyridinoporphyrazine derivatives: biological consequences in human
      erythrocytes and Escherichia coli.
AB  - The photodynamic activity of a cationic Zn(II)
      tetramethyltetrapyridinoporphyrazinium salt (ZnPc ) was compared with that of a
      non-charged Zn(II) tetrapyridinoporphyrazine (ZnPc 1), both in vitro using human
      red blood (HRB) cells and a typical Gram-negative bacterium Escherichia coli.
      Absorption and fluorescence spectroscopic studies were analyzed in different
      media. Fluorescence quantum yields (phi(F)) of 0.35 for ZnPc 1 and 0.30 for ZnPc
      2 were calculated in N,N-dimethylformamide (DMF). The singlet molecular oxygen,
      O(2)((1)Delta(g)), production was evaluated using 9,10-dimethylanthracene (DMA)
      in DMF yielding values of Phi(Delta)= 0.56 for ZnPc 1 and 0.50 for ZnPc 2. In
      biological medium, the photodynamic effect was first evaluated in HRB cells. Both
      phthalocyanines produce similar photohemolysis of HRB cells, reaching values >90%
      of lysis after 5 min of irradiation with visible light. The photodynamic effect
      is accompanied by an increase in the membrane fluidity of HRB cells. However,
      these studies on E. coli cells showed that the cationic ZnPc 2 produces a higher
      photoinactivation of Gram-negative bacteria than ZnPc 1. Also, these results were
      established by stopped of growth curves for E. coli. Therefore the studies show
      that cationic ZnPc 2 is an efficient phototherapeutic agent with potential
      applications in tumor cell and Gram-negative bacteria inactivation by
      photodynamic therapy.

PMID- 15570386
TI  - Photodegradation and phototransformation of 5,10,15,20-tetrakis(m
      hydroxyphenyl)bacteriochlorin (m-THPBC) in solution.
AB  - The kinetics of photobleaching and formation of photoproducts upon irradiation
      (735 nm) of 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) in
      phosphate buffer saline (PBS) supplemented with human serum albumin (HSA) were
      studied by means of absorption and steady-state fluorescence spectroscopy.
      Measurements were performed either immediately after the dye was dissolved in the
      HSA solution (0 h) or after six hours incubation in the HSA solution (6 h).
      Spectroscopic studies indicated that the dye was mainly present as aggregates in
      freshly prepared solutions, whereas incubation favored monomerisation.
      Irrespective to incubation time, the rates of photobleaching obtained by
      fluorescence measurements were higher than those obtained from absorbance
      measurements. Photobleaching of freshly prepared m-THPBC can be described by a
      single exponential decay, while the absorbance and fluorescence decays of the
      incubated dye solutions better fit a bi-exponential decay. Two photobleaching
      rates probably reflect differences in the photosensitivity of monomer (bound to
      proteins) and aggregated (non-bound) forms. Irradiation of the freshly prepared m
      THPBC solution led to phototransformation of 50% of the bleached m-THPBC into
      5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC), a clinically used second
      generation photosensitizer. For irradiation 6 h after dissolving m-THPBC,
      different kinetics of m-THPC formation were found. A rapid decrease in
      concentration of m-THPBC was accompanied by a slow formation of m-THPC. The
      quantum yield of this process was small since only 5% of m-THPBC was transformed
      to m-THPC. The kinetics characteristics of m-THPBC photobleaching reported in the
      present study, together with the different kinetics of photoproduct formation
      during m-THPBC photobleaching, may provide important indications in the m-THPBC
      based PDT dosimetry.

PMID- 15570387
TI  - Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide
      (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic
      absorption spectroscopy.
AB  - Palladium-bacteriopheophorbide (WST09), a novel bacteriochlorophyll derivative,
      is currently being investigated for use as a photodynamic therapy (PDT) drug due
      to its strong absorption in the near-infrared region and its ability to
      efficiently generate singlet oxygen when irradiated. In this study, we determined
      the pharmacokinetics and tissue distribution of WST09 in female EMT6 tumour
      bearing Balb/c mice in order to determine if selective accumulation of this drug
      occurs in tumour tissue. A total of 41 mice were administered WST09 by bolus
      injection into the tail vein at a dose level of 5.0 +/- 0.8 mg kg(-1). Three to
      six mice were sacrificed at each of 0.08, 0.25, 0.5, 1.0, 3.0, 6.0, 9.0, 12, 24,
      48, 72, and 96 h post injection, and an additional three control mice were
      sacrificed without having been administered WST09. Terminal blood samples as well
      as liver, skin, muscle, kidney and tumour samples were obtained from each mouse
      and analyzed for palladium content (from WST09) using graphite furnace atomic
      absorption spectroscopy (GFAAS). The representative concentration of WST09 in the
      plasma and tissues was then calculated. Biphasic kinetics were observed in the
      plasma, kidney, and liver with clearance from each of these tissues being
      relatively rapid. Skin, muscle and tumour did not show any significant
      accumulation at all time points investigated. No selective drug accumulation was
      seen in the tumour and normal tissues, relative to plasma. Thus the results of
      this study indicate that vascular targeting resulting from WST09 in the
      circulation, as opposed to selective WST09 accumulation in tumour tissues, may be
      responsible for PDT effects in tumours that have been observed in other WST09
      studies.

PMID- 15570388
TI  - Chromophore composition of a heterologously expressed BLUF-domain.
AB  - Upon heterologous expression of the BLUF (for: Blue-Light sensing Using Flavin)
      domain from AppA, a transcriptional anti-repressor from Rhodobacter sphaeroides,
      in Escherichia coli, photoactive holo-protein is formed through non-covalent
      binding of a flavin. Whereas it is generally assumed that FAD is the
      physiological chromophore of this photo-perception domain in vivo, E. coli can
      (and does) insert, depending on the growth conditions, all naturally occurring
      flavins, i.e. riboflavin, FMN and FAD into this protein domain. The nature of the
      particular flavin bound affects the photochemical- and particularly the
      fluorescence properties of the N-terminal domain of this photosensory protein.

PMID- 15570389
TI  - Water splitting with silver chloride photoanodes and amorphous silicon solar
      cells.
AB  - A thin silver chloride layer deposited on a conducting support photocatalyzes the
      oxidation of water to O(2) in the presence of a small excess of silver ions in
      solution. The light sensitivity in the visible part of the spectrum is due to
      self-sensitization caused by reduced silver species. Anodic polarization
      reoxidizes the reduced silver species. To test its water splitting capability,
      AgCl photoanodes as well as gold colloid modified AgCl photoanodes were combined
      with an amorphous silicon solar cell. The AgCl layer was employed in the anodic
      part of a setup for photoelectrochemical water splitting consisting of two
      separate compartments connected through a salt bridge. A platinum electrode and
      an amorphous silicon solar cell were used in the cathodic part. Illumination of
      the AgCl photoanode and the amorphous Si solar cell led to photoelectrochemical
      water splitting to O(2) and H(2). For AgCl photoanodes modified with gold
      colloids an increased photocurrent, and consequently a higher O(2) and H(2)
      production, were observed.

PMID- 15570390
TI  - Refractive index effects on the oscillator strength and radiative decay rate of
      2,3-diazabicyclo[2.2.2]oct-2-ene.
AB  - The photophysical properties of 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) were
      determined in 15 solvents, two supramolecular hosts (cucurbit[7]uril and beta
      cyclodextrin) as well as in the gas phase. The oscillator strength and radiative
      decay rate of DBO as a function of refractive index i.e. polarizability have been
      analyzed. The oscillator strength increases by a factor of 10 upon going from the
      gas phase to the most polarizable carbon disulfide, while the corresponding
      radiative decay rates increase by a factor of 40. There is a good empirical
      correlation between the oscillator strength of the weakly allowed n,pi*
      transition of DBO and the reciprocal bulk polarizability, which can be employed
      to assess the polarizability of unknown microheterogeneous environments. A
      satisfactory correlation between the radiative decay rate and the square of the
      refractive index is also found, as previously documented for chromophores with
      allowed transitions. However, the correlation improves significantly when the
      oscillator strength is included in the correlation, which demonstrates the
      importance of this factor in the Strickler-Berg equation for chromophores with
      forbidden or weakly allowed transitions, for which the oscillator strength may be
      strongly solvent dependent. The radiative decay rate of DBO in two supramolecular
      assemblies has been determined, confirming the very low polarizability inside the
      cucurbituril cavity, in between perfluorohexane and the gas phase. The
      fluorescence quantum yield of DBO in the gas phase has been remeasured (5.1 +/-
      0.5%) and was found to fall one full order of magnitude below a previously
      reported value.

PMID- 15570391
TI  - Poly(amidoamine) dendrimer peripherally modified with 4-N,N
      dimethylaminoethyleneamino-1,8-naphthalimide as a sensor of metal cations and
      protons.
AB  - A new poly(amidoamine) dendrimer from second generation whose periphery comprises
      sixteen fluorescent 4-N,N-dimethylaminoethylamino-1,8-naphthalimide units has
      been synthesized and characterized. In DMF, the dendrimer shows sensitivity to
      the presence of Cu(2+), Fe(3+) and protons. The changes in the fluorescence
      intensity of the material are in opposite directions if acids or metals are
      present. Fluorescence enhancements (FE from 5 to 9 depending on solvent) are
      recorded when the photoinduced electron transfer (PET) originating from the
      donating amine to the electron accepting naphthalimide is inhibited by the
      protonation of the N,N-dimethylamino groups. In the case of Cu(2+) cations, a
      fluorescence quenching (FQ of 6) is first observed, followed by fluorescence
      partial restoration. In the Fe(3+) case, the same behaviour is observed with a
      final FE of 2. The successive complexations of these cations by the dendrimer
      core and by the external rim of the dendrimer may explain the results.

PMID- 15570392
TI  - Characterisation of the lowest singlet and triplet excited states of S
      flurbiprofen.
AB  - The photophysical properties of S-flurbiprofen [S-2-fluoro-alpha-methyl-4
      biphenylacetic acid], a nonsteroidal anti-inflammatory drug, have been examined
      using steady-state and time-resolved spectroscopic techniques. The energy of its
      first singlet excited state is 99 kcal mol(-1). The fluorescence quantum yields
      and lifetimes (at 300 nm) have been determined in acetonitrile, methanol, hexane
      and PBS; they are in the range 0.15<phi(F)< 0.33 and 0.7<tau(F)<2.0 ns. The
      intersystem crossing quantum yields are between 0.45 and 0.71; the lambda(max) of
      the T-T absorption is 360 nm, and the triplets live from 15 to 106 micros. Steady
      state photolysis in aqueous medium leads to S-2-hydroxy-alpha-methyl-4
      biphenylacetic acid via photonucleophilic aromatic substitution, in addition to
      the photodecarboxylation products observed in organic solvents.

PMID- 15570393
TI  - The photochemistry of 8-bromo-2'-deoxyadenosine. A direct entry to cyclopurine
      lesions.
AB  - The UV photolysis of 8-bromo-2'-deoxyadenosine has been investigated in different
      solvents and in the presence of additives like halide anions. Photolytic cleavage
      of the C-Br bond leads to formation of the C8 radical. In methanol, subsequent
      hydrogen abstraction from the solvent is the main radical reaction; however, in
      water or acetonitrile intramolecular hydrogen abstraction from the sugar moiety,
      to give the C5' radical, is the major path. This C5' radical undergoes a
      cyclization reaction on the adenine and gives the aminyl radical. A rate constant
      of 1.8 x 10(5) s(-1) has been measured by laser flash photolysis in CH(3)CN for
      this unimolecular process. Product studies from steady-state photolysis in
      acetonitrile have shown the conversion of 8-bromo-2'-deoxyadenosine to 5',8-cyclo
      2'-deoxyadenosine in 65% yield and in a diastereoisomeric ratio (5' R):(5' S)=
      1.7. Evidence supporting that the equilibrium Br*+ Br(-)[right left harpoons]
      Br(2)*(-) plays an important role in this synthetically useful radical cascade is
      obtained by regulating the relative concentrations of the two reactive oxidizing
      species.

PMID- 15570394
TI  - Photoreactions of cisoid 1,4-diphenyl-1,3-butadienes. Direct irradiation in
      solution and in low temperature organic glass.
AB  - The photoreactions of 1,4-diphenyl-1,3-butadienes (DPB) fused with a
      bicyclo[2.2.1]heptano ring under direct irradiation were examined in solution at
      room temperature and in organic glass at liquid nitrogen temperature.
      Photocyclization yielding a phenylnaphthalene compound was shown to be preceded
      by facile E,E to E,Z photoisomerization. The reverse E,Z to E,E isomerization
      took place with equal ease in low temperature organic glass and in solution at
      room temperature. The pattern of reaction at low temperature is consistent with
      the involvement of the Hula-twist mechanism. However, complexity in
      conformational population, suggested by ab initio calculated data, made the
      experimental evidence less clear-cut than in previously reported examples of HT.

PMID- 15570395
TI  - Mechanism of photoacid generation for an arylcycloalkylsulfonium salt by ring
      opening and aryl cleavage.
AB  - The photochemistry of 1-(4-tert-butylphenyl)-tetrahydro-thiopyranium triflate
      (1), an arylcycloalkylsulfonium salt, was investigated in acetonitrile and
      methanol at low conversion in order to understand the reaction mechanism and its
      efficiency as photoacid generator. Both types of C-S bond in 1 are cleaved from
      the excited state. The heterolytic cleavage of the methylene C-S bond produces 4
      t-BuC(6)H(4)S(CH(2))(4)CH(2)(+) by ring opening. The carbocation generates acid
      and arylalkenylsufides by elimination or 1,2 hydride shift and elimination. The
      predominantly homolytic cleavage of the aryl C-S bond yields 4-t-BuC(6)H(4)* and
      c-C(5)H(10)S(+)* as the fragmentation products. The radicals react with the
      solvent forming acid, pentamethylene sulfide and tert-butylbenzene. In methanol,
      the formation of 4-tert-butylanisole indicates a contribution of solvolysis in
      the excited state of 1 or a competing formation of free aryl cation by
      heterolytic fragmentation. The acid generation efficiency of 1 in solution
      (acetonitrile or methanol) is lower than that corresponding to triphenylsulfonium
      triflate (TPS OTf) under the same conditions. This suggests a pathway for the
      regeneration of 1 after photocleavage. The photochemistry of 1 is discussed in
      terms of the contribution of fragmentation and ring opening reaction paths to its
      overall acid generation efficiency, a key property in terms of its applications
      in resist formulations.

PMID- 15570396
TI  - The jasmonate-free rice mutant hebiba is affected in the response of phyA'/phyA"
      pools and protochlorophyllide biosynthesis to far-red light.
AB  - Phytochrome (phy) A in its two native isoforms (phyA' and phyA") and the active
      (Pchlide(655)) and inactive (Pchlide(633)) protochlorophyllides were investigated
      by low-temperature fluorescence spectroscopy in the tips of rice (Oryza sativa L.
      Japonica cv Nihonmasari) coleoptiles from wild type (WT) and the jasmonate
      deficient mutant hebiba. The seedlings were either grown in the dark or under
      pulsed (FRp) or continuous (FRc) far-red light (lambda(a) >/= 720 nm) of equal
      fluences. In the dark, the mutant had a long mesocotyl and a short coleoptile,
      whereas the situation was reversed under FR: short mesocotyl and long coleoptile,
      suggesting that the effect is mediated by phyA. Under these conditions the WT
      displayed a short coleoptile and emergence of the first leaf. In the dark, the
      spectroscopic and photochemical properties of phyA, its content and the
      proportion of its two pools, phyA' and phyA", were virtually identical between WT
      and hebiba. However, the total content of protochlorophyllides was higher in the
      mutant. Upon illumination with FRc, [phyA] declined in the WT and the ratio
      between phyA' and phyA" shifted towards phyA". In hebiba, the light-induced
      decline of [phyA] was less pronounced and the ratio between phyA' and phyA" did
      not shift. Moreover, in the WT, FRp stimulated the biosynthesis of Pchlide(655),
      whereas FRc was inhibiting. In contrast, in the mutant, both FRp and FRc
      stimulated the synthesis of Pchlide(655). This means that FRc caused the opposite
      effect in hebiba. This difference correlates with a slower photodestruction of
      primarily the light-labile phyA' pool in hebiba.

PMID- 15570397
TI  - True fluorescence spectra of leaves.
AB  - True fluorescence spectra of leaves are obtained combining experimental emission
      and reflectance data. The model used is validated by measuring the system
      fluorescence in the absence of reabsorption processes (thin layer of
      chloroplasts).

PMID- 15570398
TI  - Estimations of the human 'vitamin D' UV exposure in the USA.
AB  - Human exposure to sunlight promotes the formation of pre-vitamin D in the skin.
      Low or marginal levels of vitamin D has been linked to a wide range of human
      health outcomes, including the development of various types of cancer. However,
      few data exist on the actual exposure to human due to vitamin D producing
      ultraviolet radiation. Most studies of human disease and vitamin D have linked
      latitude and location of residence to expected exposure form the available
      ambient UV radiation. Human UV exposure for the development of vitamin D depends
      on a variety of factors such as time spent outdoors, percent available skin, skin
      type, UV protective devices used and distribution of UV over the human form. In
      this paper, we investigate how latitude impacts not only on the amount of UV
      available for vitamin D synthesis, but also the distribution of UV over the human
      form.

PMID- 15570399
TI  - Gender-dependent reductions in vertebrae length, bone mineral density and content
      by doxorubicin are not reduced by dexrazoxane in young rats: effect on growth
      plate and intervertebral discs.
AB  - Doxorubicin (DOX) is widely used in anti-cancer cocktails. Dexrazoxane (DXR) is a
      cardioprotectant approved for use with DOX. The effect of DOX, with or without
      DXR, on bone in children is not well understood. The aim of this study was to
      examine the effect of DOX on vertebrae and femur length and bone density
      acquisition in young rats, as well as to test the hypothesis that young females
      are more susceptible to DOX-induced tissue damage than young males. The results
      of this study suggest that a single injection of DOX in young female and not male
      rats is associated with low bone turnover resulting in vertebrae and femur bone
      growth deficits. DOX selectively decreased BMD and BMC accrual in the lumbar
      vertebrae that was not prevented by DXR. DOX-treated rats also exhibited growth
      plate and intervertebral disc defects. This information will be useful in the
      design of interventions to promote bone growth or retard bone loss during DOX
      treatment.

PMID- 15570400
TI  - The risk of Colles' fracture is associated with the collagen I alpha1 Sp1
      polymorphism and ultrasound transmission velocity in the calcaneus only in
      heavier postmenopausal women.
AB  - To compare the ability of the bone mineral density (BMD) at the distal forearm,
      collagen I alpha 1 (COLIA1) polymorphism, and ultrasound stiffness to identify
      individuals with increased risk of wrist fracture, we studied 183 postmenopausal
      Czech women with a wrist fracture and 178 postmenopausal controls, ages 45-70
      years. The genotypes "Ss" and "ss" were significantly overrepresented among
      fracture cases. The BMD measurements at the femoral neck, total femur, and distal
      forearm as well as ultrasound stiffness of the heel, broadband ultrasound
      attenuation (BUA), and speed of sound (SOS) were significantly lower in the
      fracture cohort. BMD of the distal forearm was the main determinant of
      susceptibility to the wrist fracture. Weight, the COLIA1 genotype, and ultrasound
      SOS further strengthened the predictive value of BMD. However, we found
      interaction between weight and both the COLIA1 Sp1 polymorphism and ultrasound
      parameters. Presence of the "s" allele as well as low SOS acted as significant
      predictors of wrist fracture only in heavier women, (> or =62 kg) but not in
      women with a body weight of less than 62 kg. In heavier women, both the COLIA1
      Sp1 polymorphism and ultrasound parameters acted as independent markers that
      contributed to BMD to enhance fracture prediction. However, the COLIA1 enabled a
      higher specificity (specificity 72.4%, sensitivity 44.2%), whereas SOS enabled a
      higher sensitivity (sensitivity 73.9%, specificity, 45.7%). We conclude that BMD
      at total forearm, the COLIA1 polymorphism, and ultrasound SOS are independent
      predictors of wrist fracture in postmenopausal women. The effect of the COLIA1
      Sp1 polymorphism and SOS on wrist fracture risk is more pronounced in patients
      with a higher body weight.

PMID- 15570401
TI  - The -1997 G/T polymorphism in the COLIA1 upstream regulatory region is associated
      with hip bone mineral density (BMD) in Chinese nuclear families.
AB  - Type I collagen is the most abundant protein of bone matrix, and the collagen
      type I alpha 1(COLIA1) gene has been considered one of the most important
      candidate genes for osteoporosis. In this study, we simultaneously tested linkage
      and/or association of the -1997 G/T polymorphism in the COLIA1 upstream
      regulatory region with the variation of bone mineral density (BMD) in 1263
      subjects from 402 Chinese nuclear families, consisted of both parents and at
      least one healthy female offspring from 20 to 45 years of age. All the subjects
      were genotyped by using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). BMD of the lumbar spine (L1-L4) and hip (respective and
      combined phenotype of the femoral neck, trochanter, and intertrochanter) was
      measured by dual-energy X-ray absorptiometry (DXA). By using the tests
      implemented in program QTDT (quantitative transmission disequilibrium test), we
      found significant within-family association (via TDT) between the -1997 G/T
      polymorphism with BMD variation at all the hip sites (respective and combined
      phenotypes, P < 0.05). The amount of BMD variation explained by the -1997G/T
      polymorphism was 1.6%, 2.0%, 1.2%, and 1.3% at the total hip, femoral neck,
      trochanter, and intertrochanter, respectively. Because of the limited number of
      sib pairs in this sample, we did not find evidence of linkage. In summary, the 
      1997 G/T polymorphism in the COLIA1 gene is likely to be in linkage
      disequilibrium with a nearby functional polymorphism affecting hip BMD, or the 
      1997 G/T polymorphism itself may have an important effect on the variation of hip
      BMD in our Chinese sample.

PMID- 15570402
TI  - Overexpression of IGF-binding protein 5 alters mineral and matrix properties in
      mouse femora: an infrared imaging study.
AB  - The anabolic effects of insulin-like growth factors (IGFs) are modulated by a
      family of IGF-binding proteins (IGFBPs). Among the six known IGFBPs, IGFBP-5 is
      considered to play a role in bone formation. To investigate the effects of IGFBP
      5 on bone mineral and matrix properties, femurs from transgenic mice
      overexpressing IGFBP-5 under the control of the osteocalcin promoter were
      evaluated by Fourier Transform Infrared Imaging (FTIRI). Analyses were done at
      the time of maximal osteocalcin expression (5 weeks). The spectroscopic
      parameters monitored were mineral-to-matrix ratio (indicative of the relative
      amount of mineral present), mineral crystallinity (index of the mineral crystal
      size and perfection) and collagen maturity (reflecting the ratio of non-reducible
      and reducible collagen cross-links). Multiple fields were selected for each
      femur, ranging from epiphysis to diaphysis. Previously, we showed that these
      transgenic mice display decreased osteoblastic function and osteopenia. In the
      present work, FTIRI showed that transgenic mice as compared to wild types have a
      different pattern of bone mineralization and matrix maturation. Specifically,
      cortical bone, primary spongiosa, and secondary ossification centers had lower
      values for mineral-to-matrix ratio and collagen maturity. Differences were not
      statistically significant in all cases although the trends were consistent. The
      mineral crystallinity did not vary significantly between the two groups, implying
      that the crystal maturation of mineral was not affected by IGFBP-5
      overexpression. This study demonstrates that femurs from transgenic mice over
      expressing IGFBP-5 under the control of the osteocalcin promoter have modest
      alterations in mineral and matrix distribution, consistent with a role of IGF in
      osteoblast maturation.

PMID- 15570403
TI  - Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip
      fractures.
AB  - RANKL (receptor activator of NF-kappaB) is a potent physiological inducer of
      osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin
      (OPG), and treatment with OPG blocks bone resorption in postmenopausal women.
      Both positive and negative associations between serum OPG and bone mineral
      density (BMD) have been reported in the literature. We hypothesized that
      decreased OPG production relative to RANKL within bone itself could lead to
      increased risk of osteoporotic fracture. We included ten women with hip fracture
      (age 76.3 +/- 8.0 years, N.S, : hip BMD 0.686 +/- 1.3 g/cm2, P < 0.05) and 24
      women with osteoarthrosis of the hip (age 72.8 +/- 7.2 years, hip BMD 0.832 +/-
      1.1 g/cm(2)). Transiliac biopsies were obtained at the time of surgery. Total RNA
      was extracted from biopsies and reverse-transcribed. Real-time quantification of
      mRNA was performed with a SYBR Green I real time PCR assay, calculating relative
      gene expression with normalization of results for beta actin mRNA. Actin
      normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in
      fracture patients, with a significantly higher RANKL/OPG ratio in patients with
      fractures. There was no significant difference in tumor necrosis factor (TNF), IL
      1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients
      (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on
      fracture risk was additive to that of hip BMD T score (Z = -1.95, P < 0.05) when
      assessed using logistic regression. Elderly women with hip fractures exhibit an
      increased RANKL/OPG mRNA content of iliac bone. This is associated with increased
      fracture susceptibility, which is not in itself explained by low BMD.

PMID- 15570404
TI  - Muscle influence on postnatal craniofacial development and diagnostics.
AB  - The postnatal craniofacial development is determined by exogenous and endogenous
      factors that may result in morphological and functional muscle changes and
      influence the dentoskeletal region in terms of a physiologic or dysgnathic
      development. Using functional appliances, efforts are made to treat skeletal
      malocclusions through targeted exercise and to prevent an undesirable development
      of the dentition and the craniofacial structures. However, the success of the
      treatment and the stability of the outcome are not always adequate. To illustrate
      the treatment processes, clinically relevant measures for diagnosing muscle
      function and morphology have been developed in recent years. Electromyographic
      investigations and bite-force measurements show an excessively high variability
      and the histologic examinations applied to date are restricted in their
      suitability for analysis of the human masticatory muscles. Animal experimental
      studies have meanwhile succeeded in simulating functional jaw orthopedics and in
      demonstrating muscle remodeling processes at the genetic level. Despite some
      invasiveness, the time and the small quantity of muscle tissue involved permit
      molecular biological measuring in the orofacial system.

PMID- 15570405
TI  - Age-related changes in the midpalatal suture. A histomorphometric study.
AB  - AIM: The issue of the present study was to register age-related morphological
      differences with reference to the mean sutural width (MSW) and the degree of
      obliteration (O) in the region of the human midpalatal suture. MATERIAL AND
      METHODS: 22 human palate specimens from subjects of different ages (18-63 years)
      were available for this purpose. Three sections (anterior, median and posterior)
      from each specimen underwent histological preparation and staining with toluidine
      blue before being subjected to histological and histomorphometric analysis. Two
      age groups (< or = 25 years and > or = 26 years) were formed. RESULTS: The
      findings showed that the median sutural width in the younger group (< or = 25
      years) was 211.20 microm versus only 161.16 microm in the older group. This
      difference was statistically significant (p = 0.05). The proportion of ossified
      tissue in the entire suture (obliteration) was low in all subjects. At 13.10%,
      the maximum obliteration measured was found in a 44-year-old man in the older age
      group. The median value of the ossification was 0% in the younger age group and
      3.11% in the group > or = 26 years. This difference was statistically significant
      (p = 0.036). The earliest ossification was registered in a 21-year-old man. The
      oldest subject without ossification was a 54-year-old man. In terms of local
      topography, no statistically significant differences between anterior, median and
      posterior palatal region were observed with respect to the two investigated
      parameters (MSW, O). CONCLUSION: These findings confirm that ossification of the
      midpalatal suture is not a valid reason for the increased transversal resistance
      encountered during rapid palatal expansion in younger subjects (< or = 25 years)
      as well as in many older persons.

PMID- 15570406
TI  - A retrospective cephalometric study for the quantitative assessment of relapse
      factors in cover-bite treatment.
AB  - BACKGROUND AND AIM: Cover-bite ("Deckbiss") is regarded as a highly relapse-prone
      malocclusion. In this context the great significance of a high lip line (LipL) as
      an etiologic factor for the retroclination of the upper central incisors was
      recently proven within the framework of lip pressure measurements. It therefore
      seemed likely that a persisting high LipL after correction of cover-bite might
      have an equally negative impact on the stability of the treatment outcome.
      MATERIALS AND METHODS: This issue was investigated in the present retrospective
      study by cephalometric analysis of the findings prior to therapy (T1),
      immediately after active mechanotherapy (T2), and after a mean follow-up period
      of 2 years (T3). The study group consisted of 40 former cover-bite patients with
      initial linguoversion of the upper central incisors (axial angle to anterior
      cranial base < 98 degrees ) and anterior deep bite (> or = 4 mm) from the records
      of the Department of Orthodontics, University of Freiburg i. Br., Germany.
      RESULTS AND CONCLUSIONS: The average relapse was ca. 20% of the total correction
      of the anterior linguoversion and deep bite, with the relapse tendency, however,
      displaying substantial interindividual variations. Multiple regression analysis
      revealed an increased relapse tendency in specific cases: patients with maxillary
      extractions, cases with a pronounced therapeutically induced change of upper
      central incisor inclination, and patients with a high post-therapeutic LipL or
      with poor compliance in the retention phase. In view of the relatively good
      opportunity to influence the level of the LipL therapeutically, one of the most
      important therapeutic objectives for cover-bite patients should be to reduce the
      amount by which the lower lip overlaps the upper incisors ( to a maximum value of
      3 mm). This can be achieved by active mechanical intrusion of the upper incisors.
      If the orthodontist fails to take account of this aspect when planning or
      performing the treatment, he has to accept an increased risk of relapse.

PMID- 15570407
TI  - Case control study in the treatment of obstructive sleep-disordered breathing
      with an intraoral protrusive appliance.
AB  - BACKGROUND: Mandibular protrusive appliances have long been used to treat
      obstructive sleep apnea/hypopnea syndrome (OSAHS). Their efficacy regarding
      respiration during sleep varies greatly and remains difficult to predict. In this
      study the efficacy of a two-splint appliance on nocturnal breathing disorders,
      sleep profile, and daytime sleepiness were evaluated according to a specially
      designed treatment process. PATIENTS AND METHODS: In this study 42 consecutive
      OSAHS patients who had been fitted with a mandibular protrusive appliance
      according to a preset treatment regimen were included in a follow-up analysis.
      The diagnosis and the degree of severity of OSHAS were determined by
      polysomnography in the sleep laboratory. The treatment regimen was established
      with the sleep laboratory physician. Treatment regimen included the diagnostic
      procedure in the sleep laboratory, each patient's dental requirements, the
      fabrication of the appliance used, and the titration of the mandibular
      protrusion. After having grown accustomed to the appliance for 24.5 +/- 7.8 days,
      34 patients underwent overnight polysomnography. RESULTS: The mean apnea/hypopnea
      index decreased significantly from 19.6 +/- 12.8 to 3.3 +/- 7.8 events per hour
      to 83%; the apnea index also improved significantly, as did minimal oxygen
      saturation and the desaturation index. Changes in sleep profile did not reach
      statistical significance; the arousal index (p < 0.02) and the subjectively
      assessed daytime sleepiness (p < 0.02) decreased significantly. A therapeutically
      required AHI of below 5 events per hour was achieved in 88.2% of the patients.
      CONCLUSION: A significant improvement in the respiratory situation of the vast
      majority of OSAHS patients, particularly in their AHI, can be achieved when one
      applies the procedural steps and employs the mandibular protrusive appliance we
      describe herein.

PMID- 15570408
TI  - Corrosion of orthodontic pliers using different sterilization procedures.
AB  - AIM: The aim of this study was to investigate the corrosion resistance of
      orthodontic pliers from several manufacturers following different sterilization
      procedures, namely heat sterilization and the use of a disinfectant agent
      (Sekusept Extra N in an ultrasonic bath. MATERIAL AND METHODS: Employed in this
      study were ten distal-end cutters and ten Weingart pliers manufactured by
      Aesculap, ETM and Hu-Friedy, examined under electron microscopy for evidence of
      corrosion following 500 sterilization cycles. The corrosion data were recorded
      photographically and graphically. Metallographic microsections were prepared from
      each pair of pliers and were then analyzed by means of EDX measurements to assess
      the chemical alloy composition. RESULTS: The light and electron microscopic
      evaluation showed that both heat sterilization and high level disinfection caused
      corrosive changes on the pliers. However, the type of corrosion differed between
      the two sterilization methods. The main type of corrosion with Sekusept Extra N
      was pitting, while with heat sterilization it was surface corrosion. Heat
      sterilization was the type of corrosion that caused the most corrosive changes,
      regardless of which type of corrosion was considered. However, these results must
      be viewed critically, because pitting corrosion is obviously a more severe
      problem than surface corrosion. In comparing the pliers of various manufacturers,
      differences were noted. However, it was difficult to rank them when the correct
      maintenance regime was adhered to. The soldered joint gap was revealed to be a
      specific weak point, and that area proved to be inadequate due to qualities
      related to their production, particularly in the Hu-Friedy pliers. CONCLUSIONS:
      This study showed that heat sterilization leads to less corrosion than cold
      disinfection. Corroded pliers can be restored to a useable condition by re
      polishing, though it is important that the instructions for their care be
      strictly adhered to.

PMID- 15570409
TI  - Forced eruption with microscrew anchorage for preprosthetic leveling of the
      gingival margin. Case report.
AB  - Dental esthetics are often impaired by a disharmonious contour of the gingival
      margin in the anterior region. However, the soft tissue contour can be improved
      by orthodontic eruption of the relevant teeth prior to prosthodontic treatment.
      The successful use of an orthodontic microscrew implant as anchorage for the
      eruption appliance is demonstrated in a case report.

PMID- 15570410
TI  - Re: D. Gesch et al.: Malocclusions and clinical signs or subjective symptoms of
      temporomandibular disorders (TMD) in adults. Results of the population-based
      study of health in Pomerania (SHIP).

PMID- 15570411
TI  - [Multiple hyperpigmented facial plaques].

PMID- 15570412
TI  - Knowing your enemies: seasonal dynamics of host-social parasite recognition.
AB  - Despite its evolutionary significance, behavioural flexibility of social response
      has rarely been investigated in insects. We studied a host-social parasite
      system: the slave-making ant Polyergus rufescens and its host Formica rufibarbis.
      Free-living host workers from parasitized and from unparasitized areas were
      compared in their level of aggression against the parasite and alien
      conspecifics. We expected that a seasonal change would occur in the acceptance
      threshold of F. rufibarbis workers from a parasitized area towards the parasite,
      whereas F. rufibarbis workers from an unparasitized area would not show
      substantial changes connected with the parasite's peak in activity (raiding and
      colony-founding season). The results showed a significant adaptive behavioural
      flexibility of host species workers and are consistent with the acceptance
      threshold model's (Reeve 1989) prediction that recognition systems are not fixed
      but context-dependent. In particular, host workers from the unparasitized area
      were highly aggressive towards the parasite regardless of the season, whereas
      host workers from the parasitized area significantly increased their aggression
      towards the parasite during its raiding and colony-founding season. Being able to
      detect and possibly kill a Polyergus scout searching for host nests can be an
      effective strategy for a Formica colony to avoid being raided or usurped by a
      parasite queen.

PMID- 15570413
TI  - Augmented repair of avulsion-tear type medial patellofemoral ligament injury in
      acute patellar dislocation.
AB  - This study investigated the results of augmented repair for avulsion-tear type
      medial patellofemoral ligament (MPFL) injury performed on a total of five knees
      with initial acute lateral patellar dislocation. Augmented repair was performed
      using a medial retinaculum slip on all five knees. The average follow-up was 5.9
      years. The results were evaluated with the Insall, Aglietti, and Tria grading
      system. Three knees were classified as excellent, one knee as good, and one knee
      as fair. The mean Kujala score at follow-up was 97.6 points. Augmented repair of
      the injured MPFL for avulsion-type MPFL injury may be considered as one good
      option to prevent subsequent dislocation and subluxation.

PMID- 15570414
TI  - Reference database of biochemical markers of bone turnover for the Japanese
      female population. Japanese Population-based Osteoporosis (JPOS) Study.
AB  - The present study was conducted as a part of the Japanese Population-based
      Osteoporosis (JPOS) Study to establish reference values on the biochemical
      markers of bone turnover in the general Japanese female population over an
      applicable age range. The study recruited 3250 women aged 15-79 years, randomly
      selected from five municipalities throughout Japan, and obtained measurements of
      serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP); free and
      total forms of immunoreactive deoxypyridinoline, free pyridinolines and type I
      collagen cross-linked C-terminal telopeptide (CTx) in urine; serum intact
      parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25 (OH)2D); and bone
      density at the spine, hip and distal forearm. After excluding subjects with
      apparent or suggested abnormalities affecting bone mass, 2535 (78%) subjects were
      further analyzed. The authors presented 5-year age-specific mean values of the
      markers and mean marker levels derived from women aged 30-44 years with normal
      bone density as a healthy young adult reference. Values of the markers decreased
      with increasing age before the age of 40, increased steeply among subjects in
      their 50s, and remained elevated in the elderly. Serum calcium, phosphorus, PTH
      and 1,25 (OH)2D levels were higher in postmenopausal women than in premenopausal
      women. However, 1,25 (OH)2D was lower among early postmenopausal subjects. The
      levels of OC, BAP, CTx, PTH and 1,25(OH)2D were significantly greater for women
      with osteoporosis than for those without. The diagnostic value of the markers was
      limited as the sensitivity and specificity ranged from 55% to 60%. These findings
      will aid health professionals in the correct assessment of bone turnover status
      in Japanese women over a wide range of age.

PMID- 15570415
TI  - A triage strategy based on clinical risk factors for selecting elderly women for
      treatment or bone densitometry: the EPIDOS prospective study.
AB  - A triage strategy, based on a clinical hip fracture risk score, may be used to
      classify elderly women into three groups: one at high risk and requiring
      treatment, another needing further assessment by bone densitometry, and a third
      at low risk. We used prospective data from the EPIDOS study (7512 women older
      than 75 years and followed for an average of 3.9 years) to assess the potential
      value of such a strategy for identifying elderly women with a hip fracture risk
      twice the cohort average (i.e. > or =20 per 1000 woman-years). An individual
      fracture risk score was calculated with the final risk function (Cox model). To
      compare this strategy with systematic BMD measurement and with current European
      recommendations, we examined the number of high-risk women identified, their
      average risk levels, sensitivity for hip fracture, and the number of high-risk
      women who need to be treated to prevent one hip fracture (hypotheses: all
      identified women are treated; sensitivity is equal to the point estimate;
      treatment reduces fracture risk by 35%). A triage strategy based on age, fracture
      history since the age of 40 years, body mass index, number of instrumental
      activities of daily living for which assistance is needed, grip strength, and
      visual acuity can identify 20% of the cohort as at high risk, 75% of them from
      clinical factors only, and the rest after BMD measurements (threshold: -2.5 T
      score). The triage strategy would be significantly more sensitive than systematic
      BMD screening (51 versus 35%) and would require many fewer BMD examinations
      (10%). Compared with current recommendations, triage would identify fewer women
      (20 versus 28%) but at a significantly higher average risk of hip fracture (30
      versus 20 per 1000 woman-years). Fewer high-risk women would be treated to
      prevent one hip fracture (29 versus 41) and fewer bone densitometry tests would
      be needed (10% versus 54%). The proposed triage strategy may be a useful clinical
      tool for selecting elderly women for treatment or bone densitometry.

PMID- 15570416
TI  - Chlorinated aliphatic hydrocarbon-induced degradation of trichloroethylene in
      Wautersia numadzuensis sp. nov.
AB  - Two strains of trichloroethylene (TCE)-degrading bacteria were isolated from
      soils at polluted and unpolluted sites. The isolates, strains TE26(T) and K6,
      showed co-substrate-independent TCE-degrading activity. TCE degradation was
      accelerated by preincubation with tetrachloroethylene, cis-dichloroethylene (DCE)
      and 1,1-DCE. TCE-degrading activities of strains TE26(T) and K6 were 0.23, 0.24
      micromol min(-1) g(-1) dry cells, respectively. 16S rDNA sequences of strains
      TE26(T) and K6 were almost identical (99.7% similarity), and most closely related
      to Ralstonia basilensis (ATCC17697(T)) (98.5% similarity). From the results of
      DNA-DNA hybridizations, strain TE26(T) was genetically coherent to strain K6 (94
      and 88% hybridization), and exhibited lower relatedness to R. basilensis
      (DSM11853(T)) (44% and 15%). In addition, because of the differences in
      chemotaxonomic properties, strain TE26(T) and strain K6 appear to be distinct
      from all established species of the Ralstonia group. Based on these results and
      the proposal of transferring R. basilensis and related species to Wautersia gen.
      nov., we propose that these strains should be assigned to the genus Wautersia as
      Wautersia numadzuensis sp. nov.

PMID- 15570417
TI  - Fully automated in-tube solid-phase microextraction for liquid samples coupled to
      gas chromatography.
AB  - An online device is described in which analytes are extracted from a liquid
      sample by means of in-tube solid-phase microextraction (in-tube SPME), pulse
      released by rapid heating, and transferred to a gas chromatograph in a fully
      automated way. Switching of the sample and gas flows as well as the heating of
      the extraction tube and the valves is controlled by a remote computer system.
      Results obtained for river water and for aqueous standard solutions of
      phenanthrene are presented and are compared to the performance of standard SPME.

PMID- 15570418
TI  - Change in CT radiodensity of a colloid cyst of the third ventricle: case report
      and literature review.
AB  - A unique case is presented of a decrease in density on CT scans of a colloid cyst
      of the third ventricle with time. This occurred in the absence of any operative
      intervention in a 35-year-old woman.

PMID- 15570419
TI  - Thrombosis of aggressive dural arteriovenous fistula after incomplete
      embolization.
AB  - We report the cases of three patients diagnosed with dural arteriovenous fistula
      (DAVF) and cortical venous reflux (CVR). All were treated by transarterial
      endovascular embolization. Residual shunting and cortical venous drainage
      continued to be present at the end of the treatment procedure, despite the fact
      that during endovascular embolization glue penetration into the proximal venous
      component of the fistula had been achieved. Subsequently, follow-up angiography
      showed total obliteration of the fistulas and absent associated CVR. The fistulas
      were no longer opacified, and no additional treatment was performed. We
      demonstrate that residual aggressive DAVF may progress to total thrombosis if
      strategic deposition of the glue into the venous side has been achieved. Early
      follow-up angiogram is recommended prior to a planned complementary surgical
      approach.

PMID- 15570420
TI  - Postpartum cerebral angiopathy: atypical features and treatment with intracranial
      balloon angioplasty.
AB  - Postpartum cerebral angiopathy (PCA) is an uncommon cause of ischemic and
      hemorrhagic stroke in young women. It is usually clinically benign and not
      relapsing. We describe a patient with nonhemorrhagic PCA who had an atypical
      progressive neurological deficit from bilateral hemisphere watershed ischemia
      despite treatment with aggressive medical therapy and intracranial balloon
      angioplasty.

PMID- 15570421
TI  - Five-year evolution of a telangiectatic osteosarcoma initially managed as an
      aneurysmal bone cyst.
AB  - We present the clinical, radiographic, and pathologic features of a
      telangiectatic osteosarcoma (TOS) of the right femoral neck in a 20-year-old man
      which was initially diagnosed and managed as an aneurysmal bone cyst (ABC). The
      lesion recurred twice. At the second recurrence TOS was diagnosed. The first
      local recurrence was recognized 4 years 8 months after the first operation. The
      clinical diagnosis for the recurrent lesion was recurrent ABC, and curettage and
      bone graft with internal fixation were performed. The second local recurrence was
      observed 8 months after the second surgery. The right lesser trochanter appeared
      destroyed on the radiograph, and a large medial soft tissue mass was demonstrated
      by computed tomography. The patient underwent wide resection of the tumor with
      prosthetic replacement of the right proximal femur. The histologic section for
      this lesion showed a blood-filled cystic lesion, and its wall contained
      sarcomatous cells with atypical mitoses and tumor osteoid. The histologic
      diagnosis for the second recurrent lesion was high-grade TOS. The retrospective
      review of the histologic section for the primary lesion showed similar features
      to ABC except for a few bizarre cells without mitosis in the tissue of cystic
      wall. The patient demonstrates no evidence of disease 13 months after the last
      surgery without adjuvant therapy (he declined chemotherapy).

PMID- 15570422
TI  - Soft tissue telangiectatic osteosarcoma in a young patient: imaging and
      immunostains.
AB  - Telangiectatic osteosarcoma of the soft tissue is rare and generally affects
      adults older than 50 years of age. We present the case of a 17-year-old male who
      developed a mass in the right thigh. The CT and MRI findings suggested a
      malignant hemorrhagic tumor without discernable osteoid matrix. Differential
      diagnosis included various hemorrhagic mesenchymal tumors. Histology revealed
      large multiple cysts lined with septae and filled with numerous giant cells,
      pleomorphic spindle cells, and occasionally an osteoid-like substance.
      Immunostaining for osteocalcin was positive in the cytoplasm of both stromal
      mononucleate and multinucleate giant cells. Surgery and adjuvant chemotherapy
      were applied and the patient survives to the time of writing after 30 months of
      follow-up without recurrence or metastasis.

PMID- 15570423
TI  - T-cell receptor BV gene usage in colorectal carcinoma patients immunised with
      recombinant Ep-CAM protein or anti-idiotypic antibody.
AB  - The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma
      (CRC). In the present study, a recombinant Ep-CAM protein or a human anti
      idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination,
      was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant
      cytokine. A cellular immune response was assessed by measuring anti-Ep-CAM
      lymphoproliferation, IFN-gamma production (ELISPOT) and by analysing the TCR BV
      gene usage within the CD4+ and CD8+ T-cell subsets followed by CDR3 fragment
      analysis. A proliferative and/or IFN-gamma T-cell response was induced against
      the Ep-CAM protein in eight out of nine patients, and against Ep-CAM-derived
      peptides in nine out of nine patients. Analysis of the TCR BV gene usage showed a
      significantly higher usage of BV12 family in CD4+ T cells of patients both before
      and after immunisation than in those of healthy control donors (p<0.05). In the
      CD8+ T-cell subset, a significant (p<0.05) increase in the BV19 usage was noted
      in patients after immunisation. In individual patients, a number of TCR BV gene
      families in both CD4+ and CD8+ T cells were over-expressed mainly in post
      immunisation samples. Analysis of the CDR3 length polymorphism revealed a higher
      degree of clonality in post-immunisation samples than in pre-immunisation
      samples. In vitro stimulation with Ep-CAM protein confirmed the expansion of anti
      Ep-CAM T-cell clones. The results indicate that immunisation with the Ep-CAM
      protein and/or anti-Id entails the induction of an anti-Ep-CAM T-cell response in
      CRC patients, and suggest that BV19+ CD8+ T cells might be involved in a vaccine
      induced immune response.

PMID- 15570424
TI  - Control of Atm-/- thymic lymphoma cell proliferation in vitro and in vivo by
      dexamethasone.
AB  - AIM: Ataxia telangiectasia (A-T) is an autosomal recessive disease in humans
      caused by mutations in the Atm (A-T mutated) gene. The disease involves multiple
      organ systems, and is associated with a high incidence of leukemias and lymphomas
      that develop in childhood. We have reported previously that thymic lymphoma
      development in Atm knockout (Atm-/-) mice is associated with elevated spontaneous
      DNA synthesis in thymocytes, and that dexamethasone (Dex) attenuates the elevated
      DNA synthesis and prevents thymic lymphoma development. The primary objectives of
      the present study were (1) to investigate possible mechanisms underlying the
      tumor-suppressing effect of Dex on Atm-/- thymic lymphoma cells, and (2) to
      determine whether Dex is an effective tumor-suppressing treatment in mice bearing
      transplanted Atm-/- thymic tumors. METHODS: Establishment of a number of Atm-/-
      thymic lymphoma (ATL) cell lines from Atm-/- mice, cell proliferation assays,
      cell cycle analyses, Western blotting and Hoechst nuclear staining were used to
      analyze the effects of Dex on Atm-/- thymic lymphoma cells. Atm-/- tumor cells
      were transplanted into the right flanks of Atm+/+ mice prior to the initiation of
      Dex treatment. RESULTS: Atm-/- tumor cells were highly sensitive to Dex, both in
      culture and in vivo as ectopic tumors in mice. In cultured ATL-1 cells, Dex
      induced apoptosis, arrested the cell cycle at the G1 phase and downregulated NF
      kappaB and multiple cell cycle regulators, while upregulating the NF-kappaB
      inhibitor IkappaBalpha. In Atm+/+ mice transplanted subcutaneously with ATL-1
      cells, tumor growth was either prevented completely or significantly suppressed
      by Dex treatment. CONCLUSIONS: Our findings identify potential mechanisms by
      which Dex affects the proliferation and survival of ATL-1 cells in culture, and
      provide evidence that Dex can suppress the proliferation of Atm-/- thymic
      lymphoma cells growing in the body. Together these results add to our earlier
      published data suggesting that the cellular pathways regulated by Dex may be
      promising therapeutic targets for prevention and treatment of thymic lymphomas in
      A-T individuals.

PMID- 15570425
TI  - Current knowledge about physiotherapeutic strategies in osteoporosis prevention
      and treatment.
AB  - In treating patients with osteoporosis, one option in physiotherapy is to comply
      with given physical norms by using physical stimuli to influence biological
      functions and structures (bone, muscle) for adaptation, stimulation, and
      regeneration. Serial physical stimuli can also be used for interventions and
      actions to minimise pain perception by means of biopsychosocial influence. In
      osteoporosis, physiotherapy has to be rated on a par with pharmacotherapy with
      respect to prevention, cure, and rehabilitation. Generally, two different aims
      can be defined: (1) those which can be achieved with physical therapy alone, such
      as structural improvement of the existing and pharmacologically increased bone
      tissue, slowing down of round-back formation, and fall prophylaxis and (2) those
      which can be achieved with physiotherapy and pharmacotherapy, such as effective
      pain relief and increased bone density. Regulation and normalisation of physical
      capacities with an aim towards maintenance and economisation of functions and
      improvement in abilities call for a skillful and case-specific use of
      physiotherapy.

PMID- 15570426
TI  - Ameliorative effect of ozone on cytokine production in mice injected with human
      rheumatoid arthritis synovial fibroblast cells.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      invasion of hyperplastic synovial cells and progressive joint destruction. Ozone
      therapy has been proposed as an immunomodulator and cellular metabolic activator
      which shows long-term anti-inflammatory effects and serves to reduce further the
      proinflammatory factors. We purified RA synovial fibroblast cells (RA-SFc) from
      patients and avoided contaminating macrophages by flow cytometry, then treated
      them with ozone. Following the observable decreased production of proinflammatory
      factors TNF-alpha, IL-1beta, and IL-6 from RA-SFc, we infused the cultured RA-SFc
      into joints of severe combined immunodeficiency mice. The mRNA and protein levels
      of the RA-SFc exposed to 3% and 5% ozone were the same. As a result, 3% and 5%
      ozone applied externally ameliorated the inflammatory reaction of RA without
      toxicity or serious side effects. Therefore, ozone injected into the knees of RA
      patients could become a valuable treatment, and we confirm the interactive
      mechanism between ozone and RA-SFc.

PMID- 15570427
TI  - Facial nerve palsy in posterior fossa arachnoid cysts: report of two cases.
AB  - CASE REPORT: Two patients with a posterior fossa arachnoid cyst responsible for
      isolated facial nerve palsy are reported. DISCUSSION: The relationships between
      the cyst and the facial nerve and between the facial nerve palsy and the size
      variation of the cyst are discussed and documented by pre- and postoperative
      magnetic resonance imaging.

PMID- 15570428
TI  - Decrease of parafollicular thyroid C-cells in experimental esophageal atresia:
      further evidence of a neural crest pathogenic pathway.
AB  - Adriamycin-induced experimental esophageal atresia (EA) is often associated with
      malformations of neural crest (NC) origin, such as abnormal pharyngeal pouch
      derivatives like the thymus and the parathyroids. The aim of the present study
      was to examine whether NC-derived thyroid C-cells were abnormal in a rat model.
      Pregnant rats received intraperitoneally either 2 mg/kg Adriamycin (EA) or
      vehicle (controls) on days 8 and 9 of gestation. Fetuses were recovered on day
      21, and blocks including the trachea and thyroid were fixed in formalin,
      coronally sectioned at 3-mum widths, and stained with standard hematoxylin and
      eosin until the largest area of thyroid was reached. From this point on, the 1st,
      10th, and 20th slices were immunohistochemically stained with anti-calcitonin
      antibody. Positively-stained cells in each section of the gland were counted
      using a computer-assisted image analysis method, and the results were averaged.
      The distribution of the cells within the gland was assessed as well. Comparisons
      between EA and control rats were made by nonparametric tests with a significance
      threshold of p<0.05. The number of C-cells was dramatically reduced in EA animals
      compared with controls (32.4+/-36 vs. 92.3+/-60.5, p<0.001). Histology of the
      thyroid was similar in both groups, but the distribution of positive C-cells
      within the gland followed an abnormal pattern in EA rats. Adriamycin causes a
      pattern of NC-derived malformations, including a severe decrease in thyroid C
      cells accompanied by abnormal distribution or migration patterns. These results
      represent further evidence of the involvement of NC organogenic control
      dysregulation in the pathogenesis of EA and its associated malformations. The
      similarities between the rat model and the clinical picture strongly support
      investigating other subclinical NC-derived anomalies in patients with EA.

PMID- 15570429
TI  - Regional differences in nitrergic neuronal density in the developing porcine
      urinary bladder.
AB  - Nitric oxide (NO) is involved in normal bladder physiology by regulating local
      arteriolar tone and smooth muscle relaxation and modulating the production of
      extracellular matrix proteins in vitro. Little information is available regarding
      the nitrergic innervation of the bladder during development. In this study we
      investigated the changes in density and morphology of the intramural nitrergic
      neurons of the porcine urinary bladder during development using whole-mount
      preparation. Bladder specimens were obtained from porcine foetuses of gestational
      age 60 days (n=5) and 90 days (n=5) and from newborn piglets (n=5) after
      perfusion fixation. Bladders were divided into base, body, and dome. Whole-mount
      preparation using NADPH-diaphorase (NADPH-d) histochemistry was used to visualize
      nitrergic innervation of the urinary bladders and to measure density of NADPH
      positive ganglia (including single neurons), number of NADPH-d positive neurons
      per ganglion, and size of individual neurons. One-way ANOVA and chi-square tests
      were used for statistical analysis with a p-value <0.05 considered statistically
      significant. NADPH-d positive ganglia were numerous in the muscular layer of all
      three age groups. At E60, ganglion density was significantly higher in the body
      (mean 880/cm(2)) than in the dome (397/cm(2)) or the base (676/cm(2)). The
      ganglion density significantly decreased with age. The number of NADPH-d positive
      neurons per ganglion increased significantly between E90 and birth (p<0.01). A
      marked increase in the size of individual neurons over time was also seen
      (p<0.001), predominantly due to an increase in cytoplasm. Our data on whole-mount
      preparations demonstrate that significant maturation in nitrergic neuronal
      density and morphology occurs in the porcine urinary bladder, at least until
      birth.

PMID- 15570431
TI  - MAGE-A3 is a frequent tumor antigen of metastasized melanoma.
AB  - MAGE-3 or MAGE-A3 is one of the best-characterized tumor antigens. Due to its
      tumor-restricted expression pattern and its recognition by both cytotoxic and
      helper T cells it constitutes a promising tumor antigen for anticancer
      immunotherapy, notably of malignant melanoma. Surprisingly, however, only very
      limited information is available on the frequency and consistency of its
      expression in metastatic melanoma lesions. We have now investigated the presence
      of MAGE-A3 mRNA in 316 tumor samples from 147 melanoma patients by RT-PCR. MAGE
      A3 mRNA was detectable in 62% of metastases, and expression did not depend on the
      site of the metastases (skin, lymph node, and internal organs), age, sex, or
      duration of disease. Southern blot hybridization of the PCR product enhanced
      sensitivity of detection, and 26% more samples (13/50 samples tested) scored
      positive, indicating an even higher MAGE-A3 mRNA frequency than determined by
      simple ethidium bromide gel analysis. In 62 patients, we were able to investigate
      MAGE-A3 expression in several metastases from the same patient, and unexpectedly,
      both MAGE-A3-positive and MAGE-A3-negative metastases were found in 32% of these
      patients (20 of 62). Immunohistochemistry (using mAb 57B) demonstrated that the
      expression pattern was usually also heterogeneous with positively and negatively
      stained tumor cells within one metastasis. However, most (90%) of the metastases
      (47/52) gave a partially positive signal. Taken together, MAGE-A3 is a common and
      frequent tumor antigen in metastasized melanoma, but its expression is often
      heterogeneous.

PMID- 15570432
TI  - Occupation-specific screening for future sickness absence: criterion validity of
      the trucker strain monitor (TSM).
AB  - BACKGROUND: Monitoring psychological job strain may help occupational physicians
      to take preventive action at the appropriate time. For this purpose, the 10-item
      trucker strain monitor (TSM) assessing work-related fatigue and sleeping problems
      in truck drivers was developed. OBJECTIVES: This study examined (1) test-retest
      reliability, (2) criterion validity of the TSM with respect to future sickness
      absence due to psychological health complaints and (3) usefulness of the TSM two
      scales structure. METHODS: The TSM and self-administered questionnaires,
      providing information about stressful working conditions (job control and job
      demands) and sickness absence, were sent to a random sample of 2000 drivers in
      1998. Of the 1123 responders, 820 returned a completed questionnaire 2 years
      later (response: 72%). RESULTS: The TSM work-related fatigue scale, the TSM
      sleeping problems scale and the TSM composite scale showed satisfactory 2-year
      test-retest reliability (coefficient r=0.62, 0.66 and 0.67, respectively). The
      work-related fatigue, sleeping problems scale and composite scale had
      sensitivities of 61, 65 and 61%, respectively in identifying drivers with future
      sickness absence due to psychological health complaints. The specificity and
      positive predictive value of the TSM composite scale were 77 and 11%,
      respectively. The work-related fatigue scale and the sleeping problems scale were
      moderately strong correlated (r=0.62). However, stressful working conditions were
      differentially associated with the two scales. CONCLUSIONS: The results support
      the test-retest reliability, criterion validity and two-factor structure of the
      TSM. In general, the results suggest that the use of occupation-specific
      psychological job strain questionnaires is fruitful.

PMID- 15570433
TI  - Low molecular weight heparin-induced skin necrosis-a systematic review.
AB  - BACKGROUND: Low molecular weight heparins (LMWHs) are currently used as a
      standard for anti-thrombotic therapy. Skin necrosis caused by LMWH is a rare and
      probably under-reported complication. The aim of our systematic review is to
      analyse the present literature for cases of LMWH-induced skin necrosis,
      emphasising the pathogenesis, clinical pattern, and management of this rare side
      effect. METHODS: We performed a Medline literature search (PubMed database) and
      manual cross-referencing to identify all articles related to LMWH-induced skin
      necrosis. Data were analysed for type of LMWH used, time until skin necrosis
      occurred, localisation, size, laboratory findings, switch anticoagulant,
      complications, and outcome. Additionally, the case of a patient from our hospital
      is presented. RESULTS: We included a total of 20 articles (21 cases) reporting on
      LMWH-induced skin necrosis. Skin necrosis occurred locally and distant from the
      injection site. Heparin-induced antibodies were frequently observed (positive
      9/11 articles, negative 2/11). However, severe thrombocytopenia (platelet count
      <100,000 cells/ml) occurred in only four cases, while platelet count remained
      normal in 50% of the cases. After patients had been switched to other anti
      thrombotic drugs, the clinical course was usually benign; however, reconstructive
      surgery was necessary in two cases. CONCLUSION: LMWH-induced skin necrosis may
      occur as part of the heparin-induced thrombocytopenia (HIT) syndrome, but other
      pathomechanisms, including allergic reactions and local trauma, may also be
      involved. When HIT is excluded, unfractionated heparin is a safe switch
      anticoagulant. Otherwise, non-heparin preparations such as hirudin or
      fondaparinux should be preferred.

PMID- 15570434
TI  - Mucolipin 1: endocytosis and cation channel--a review.
AB  - Mucolipidosis type IV (MLIV) is a neurodegenerative, recessive, lysosomal storage
      disorder characterized by psychomotor retardation and visual impairment due to
      various ophthalmologic abnormalities. MLIV is found in relatively high frequency
      in the Ashkenazi Jewish population. The disease is caused by mutations in the
      gene MCOLN1, which encodes the protein mucolipin 1 (MLN1), a member of the
      mucolipins family. MLN1 is a non-specific cation channel, and its putative
      structure attributes it to the TRP superfamily; thus, the gene is also referred
      as TRPML1. Over 16 MLIV-causing mutations, including two founder mutations in the
      Ashkenazi population, have been identified hitherto. Atypical increased lysosomal
      storage in MLIV is present in the cells of all patients. This accumulation is
      caused by an abnormal endocytosis process of the membrane components to late
      endosomes to the lysosomes, resulting in an apparent block in the traffic process
      in pre-lysosomal vacuoles with intraluminal pH of >5.0. MLN1 was localized in
      cultured cells to late endosomes and lysosomes. The exact function of this cation
      channel in the late stages of lysosomal maintenance is currently under study.

PMID- 15570435
TI  - Awake stereotactic biopsy of brain stem lesions: technique and results.
AB  - BACKGROUND: Brain stem lesions are a heterogenous pathological group. In adults,
      pre-operative radiological diagnoses prove to be wrong in 10 to 20% of cases. It
      is therefore imperative to have a tissue diagnosis for appropriate therapeutic
      measures. Unless these lesions have a sizeable exophytic component, open biopsy
      and/or resection is marred by low diagnostic yield and prohibitive
      mortality/morbidity rates. METHODS: We describe our experience with awake
      stereotactic biopsy of brain stem lesions. Keeping the patient awake and
      monitoring clinically during the procedure allows us to make necessary changes in
      the trajectory of the biopsy probe to minimize the morbidity. A series of 13
      brain stem lesions were stereotactically biopsied using CT guidance. Seven had
      midbrain lesions; four had pontine and two had Ponto-medullary lesions. A
      frontal, pre-coronal, transcortical trajectory was used in all patients.
      FINDINGS: Histological diagnosis was established in all but one patient. There
      was no procedural mortality, and morbidity was minimal and temporary, occurring
      in three patients. CONCLUSION: Awake stereotactic biopsy is a safe technique when
      combined with clinical monitoring.

PMID- 15570436
TI  - Spinal epidural abscess: prognostic factors and comparison of different surgical
      treatment strategies.
AB  - BACKGROUND: Spinal epidural abscess (SEA) is a rare but potentially devastating
      disease requiring immediate surgical intervention and appropriate antibiotic
      treatment. The standard approach to decompress SEA is laminectomy. No report
      covers comprehensively the indications for the less invasive interlaminar
      approach, the usefulness of intra-operative ultrasonography and the suspected
      benefit of inserting a suction-irrigation drainage. METHOD: A retrospective
      evaluation of the medical and radiological data was undertaken in 27 consecutive
      patients with SEA operated on during a period of 10 years by a dorsal approach.
      Factors influencing outcome were evaluated with special regard to different
      surgical strategies concerning the invasiveness of the operative approach, the
      use of intra-operative ultrasound and the use of different drainage systems.
      FINDINGS: Outcome was mainly determined by the pre-operative neurological
      condition and the localization of the abscess. Recurrence rate was dependent on
      the longitudinal extent of the mass and the intra-operative finding of
      granulation tissue, but not on the administration of a postoperative suction
      irrigation drainage. An interlaminar approach was equally matched to a
      decompression by laminectomy in lumbar SEA concerning the incidence of
      residual/recurrent abscess formation. In concomitant spondylodiscitis,
      laminectomy bore the risk of the formation of a postoperative kyphotic deformity.
      The use of intra-operative ultrasound allowed the visualization of hidden
      inflammatory masses and, thus, reduced the rate of residual abscess formation.
      CONCLUSION: An interlaminar approach should be considered instead of laminectomy
      in lumbar SEA and in impending anterior column instability due to spondylitis.
      Intra-operative ultrasound is a beneficial aid for the determination of the
      extent of decompression during surgery and is practicable even through a narrow
      interlaminar bony window. The insertion of postoperative suction-irrigation
      drainage had no beneficial effect on outcome but bore the risk of epidural fluid
      congestion.

PMID- 15570437
TI  - Management of pituitary apoplexy: clinical experience with 40 patients.
AB  - BACKGROUND: Pituitary apoplexy is a rare major clinical event with neurological,
      neuro-ophthalmological, cardiovascular and hormonal consequences, resulting from
      an acute infarction of pituitary adenoma. We report our experience with a series
      of 40 patients presenting with pituitary apoplexy. PATIENTS: Forty patients (27
      males, 13 females; mean age, 51.2 yr) were admitted to our medical center between
      years 1985-2002 with acute presentation of pituitary apoplexy. Visual field
      defects occurred in 61% and ocular paresis in 40% of subjects. Sixty-three
      percent of adenomas were nonfunctional, and prolactinomas comprised 31%. RESULTS:
      Thirty-four patients underwent transsphenoidal pituitary decompression. Visual
      fields and ophthalmoplegia improved in 81% and 71%, respectively. During follow
      up (4.5+/-5.4 yr), 79% of patients developed hypogonadotrophic hypogonadism,
      central hypothyroidism appeared in 54% and hypocortisolism--in 40% of patients.
      Permanent diabetes insipidus was diagnosed in 8%. Serial sellar MRI showed
      disappearance of pituitary tumor in 63% of operated subjects. Six patients (3
      with PRL-secreting and 3 nonfunctional adenomas) were treated medically
      (corticosteroids, dopamine agonists), two patients (out of three) with visual
      deficits improved, and tumor shrinkage was noted in four. CONCLUSIONS: We present
      a large series of patients with pituitary apoplexy. Most subjects were operated,
      but six were treated conservatively. Almost all patients improved clinically,
      including those who were not operated, but hormonal deficiencies are very common.

PMID- 15570438
TI  - Spontaneous acute subdural haematoma caused by tension pneumocephalus.
AB  - We describe the first case of spontaneous acute subdural haematoma (SASH) caused
      by tension pneumocephalus in a patient who had undergone surgery for sinusitis
      followed by meningitis many years previously. The patient presented with a
      seizure and epistaxis. The haematoma was caused by a torn bridging vein. Tension
      pneumocephalus has to be added to the list of possible causes for SASH.

PMID- 15570439
TI  - Spontaneous ventriculostomy in a patient with obstructive hydrocephalus.
AB  - BACKGROUND: Spontaneous ventriculostomy related to progressive obstructive
      hydrocephalus is rare. Radiologic demonstration of such a phenomenon can be
      delineated with magnetic resonance imaging (MRI) and cine MRI. CASE PRESENTATION:
      A 59-year-old woman with a known tectal glioma and symptoms of chronic
      hydrocephalus developed progressively worsening headaches. During follow-up, she
      noted spontaneous relief of her headaches. Follow-up cine MRI demonstrated a
      spontaneous ventriculostomy via the floor of the third ventricle. INTERPRETATION:
      Clinicians should be aware of spontaneous ventriculostomy demonstrable on cine
      MRI because it may obviate the need for a CSF diversion procedure.

PMID- 15570440
TI  - Multimodal strategy for managing meningiomas in the elderly.
AB  - BACKGROUND: The incidence of brain tumors in elderly patients is increasing. It
      has become possible to treat meningiomas in the elderly by several modalities. We
      developed a successful multimodal strategy to treat these patients. METHODS: We
      registered 35 patients with meningiomas. Symptomatic meningiomas were treated
      surgically at the time of diagnosis (n=19). Of the 16 asymptomatic meningiomas, 5
      were removed at the time of diagnosis. The other asymptomatic meningiomas (n=11)
      were treated conservatively and when the tumors increased in size, surgical
      treatment was considered. "Operated" patients with residual or recurrent tumors
      underwent radiosurgery with a gamma knife. FINDINGS: Surgical mortality and
      morbidity were 4% and 16%, respectively. Of the 25 "operated" patients, 21
      (84.0%) had a good Karnofsky scale (> or =80%) at discharge. In all but two of
      the 11 patients with asymptomatic, conservatively treated meningiomas, the tumors
      did not increase during the follow-up period. Gamma knife radiosurgery, performed
      to treat 3 residual and 1 recurrent tumor, resulted in very good tumor control
      and none of the tumors increased after gamma knife surgery. CONCLUSIONS:
      Meningiomas in elderly patients require a multimodal approach. Our strategy,
      which includes surgery, radiosurgery, and conservative treatment, resulted in
      good tumor control and made it possible for patients to pursue their activities
      of daily life.

PMID- 15570441
TI  - The relationship of intracranial pressure Lundberg waves to electroencephalograph
      fluctuations in patients with severe head trauma.
AB  - Lundberg (or B) waves, defined as repetitive changes in intracranial pressure
      (ICP) occurring at frequencies of 0.5 to 2 waves/min, have been attributed to
      cerebral blood flow fluctuations induced by central nervous system pace-makers or
      cerebral pressure autoregulation. We prospectively recorded and digitalized at a
      frequency rate of 10 Hz (AcqKnowledge software) the following parameters in 6
      brain injured patients: mean arterial pressure, heart rate, ICP, mean flow
      velocity of the middle cerebral artery (MFVMCA) (transcranial Doppler WAKI) and
      left and right spectral edge frequency (SEFl, SEFr) of continuous
      electroencephalogram (EEG) recordings (Philips technologies). All patients were
      sedated using a combination of sufentanil and midazolam and mechanically
      ventilated. Cerebral electrical activity (oscillations of SEF at a mean frequency
      of 26+/-9 mHz) and MFVMCA fluctuations were found strongly correlated with the
      intracranial Lundberg B waves (mean frequency 23+/-7 mHz). These result support
      the existence of a neuropacemaker at the origin of the Lundberg B waves. The
      change in cerebral electrical activity, resulting from cerebral pacemakers, could
      increase cerebral metabolic rate of oxygen (CMRO2) and thus lead to an increase
      in cerebral blood flow and secondarily of ICP through a change in cerebral blood
      volume.

PMID- 15570442
TI  - Report and review on the achievements and future plans of the ILAR Standing
      Committee for Health Professionals.

PMID- 15570446
TI  - Solid-state structure of polypeptide-based rod-coil block copolymers: folding of
      helices.
AB  - This work compares the solid-state structures of films made from a polystyrene
      poly(Z-L-lysine) (1) and a polystyrene-poly(gamma-benzyl-L-glutamate) (2) block
      copolymer, both having virtually the same numbers of repeating units and block
      length ratios. Small-angle X-ray scattering (SAXS) revealed a hexagonal-in
      undulated lamellar morphology for both films. The long-period and the thickness
      of layers obtained for 2 were by a factor of three smaller as compared to 1,
      indicating that PBLGlu helices were folded twice, whereas PZLLys helices were
      fully stretched. Another difference shows up in the packing of helices, the level
      of ordering being considerably lower in 2. This might be due to spatial
      restrictions in the proper alignment of back-folded helical segments.

PMID- 15570447
TI  - The interplay between screening properties and colloid anisotropy: towards a
      reliable pair potential for disc-like charged particles.
AB  - The electrostatic potential of a highly charged disc (clay platelet) in an
      electrolyte is investigated in detail. The corresponding non-linear Poisson
      Boltzmann (PB) equation is solved numerically, and we show that the far-field
      behaviour (relevant for colloidal interactions in dilute suspensions) is exactly
      that obtained within linearized PB theory, with the surface boundary condition of
      a uniform potential. The latter linear problem is solved by a new semi-analytical
      procedure and both the potential amplitude (quantified by an effective charge)
      and potential anisotropy coincide closely within PB and linearized PB, provided
      the disc bare charge is high enough. This anisotropy remains at all scales; it is
      encoded in a function that may vary over several orders of magnitude depending on
      the azimuthal angle under which the disc is seen. The results allow to construct
      a pair potential for discs interaction, that is strongly orientation dependent.

PMID- 15570448
TI  - Lycopene accumulation and cyclic carotenoid deficiency in heterotrophic Chlorella
      treated with nicotine.
AB  - We studied the effects of nicotine on Chlorella regularis Y-21 grown under
      heterotrophic conditions. Nicotine repressed growth, doubled cell size, and
      changed the culture coloration from dark-green to orange. These effects are
      likely due to the change of the chloroplast into a red irregular vesicle. This
      morphological change was associated with alteration of the carotenoid
      composition. Lycopene accounted for more than 80% of total carotenoids in
      nicotine-treated cells. The red irregular vesicles had a high electron density;
      we supposed them to be immature chloroplasts accumulating lycopene.

PMID- 15570445
TI  - Endoscopic third ventriculostomy for obstructive hydrocephalus.
AB  - The indications for neuroendoscopy are not only constantly increasing, but even
      the currently accepted indications are constantly being adjusted and tailored.
      This is also true for one of the most frequently used neuroendoscopic procedures,
      the endoscopic 3rd ventriculostomy (ETV) for obstructive hydrocephalus. ETV has
      gained popularity and widespread acceptance during the past few years, but little
      attention has been paid to the techniques of the procedure. After a short
      introduction describing the history of ETV, an overview is given of all the
      different techniques that have been and still are employed to open the floor of
      the 3rd ventricle. The spectrum of indications for ETV has been widely enlarged
      over the last years. Initially, the use of this procedure was restricted to
      patients older than 2 years, to patients with an obvious triventricular
      hydrocephalus, and to those with a bulging, translucent floor of the 3rd
      ventricle. Nowadays, indications include all kinds of obstructive hydrocephalus
      but also communicating forms of hydrocephalus. The results of endoscopic
      procedures in treating these pathologies are given under special consideration of
      shunt technologies. In summary, from the review of the publications since the
      first ETV performed by Mixter in 1923, this technique is the treatment of choice
      for obstructive hydrocephalus caused by different etiologies and is an
      alternative to cerebrospinal fluid shunt application.

PMID- 15570449
TI  - Antiviral Research - 15th International Conference. 17-21 March 2002, Prague,
      Czech Republic.
AB  - The 15th International Conference on Antiviral Research, organized by the
      International Society for Antiviral Research (ISAR), was held in Prague. Around
      320 participants attended the meeting. In over 160 presentations, the latest
      preclinical and early clinical data on the development of new antiviral agents
      were presented. A satellite symposium entitled 'Clinical update on antiviral
      drugs' preceded the main meeting program. The conference was jointly chaired by
      Antonin Holy (Institute of Organic Chemistry and Biochemistry, Czech Republic) as
      the local representative and Earl Kern (University of Alabama at Birmingham, USA)
      of the ISAR Conference Committee. New agents that target distinct steps of the
      HIV life cycle were presented. Notably, novel HIV entry inhibitors acting on a
      post-binding step, a series of N-aminoimidazole derivatives blocking reverse
      transcriptase or post integrase events, and innovative strategies aimed at
      avoiding HIV drug resistance to reverse transcriptase (RT) inhibitors were
      described at the meeting. In this report, oral and poster presentations dealing
      with anti-HIV and antiretroviral agents in the development pipeline are
      discussed.

PMID- 15570450
TI  - Antiviral Research - 15th International Conference. Mega-HAART and tenofovir. 17
      21 March 2002, Prague, Czech Republic.

PMID- 15570451
TI  - Antiviral Research - 15th International Conference. HBV and HCV therapies. 17-21
      March 2002, Prague, Czech Republic.

PMID- 15570452
TI  - Antiviral Research - 15th International Conference. The herpesviruses. 17-21
      March 2002, Prague, Czech Republic.

PMID- 15570453
TI  - Antiviral Research - 15th International Conference. Symposium highlights. 17-21
      March 2002, Prague, Czech Republic.

PMID- 15570454
TI  - American Association for Cancer Research - 93rd Annual Meeting. 6-10 April 2002,
      San Francisco, CA, USA.

PMID- 15570455
TI  - American Association for Cancer Research - 93rd Annual Meeting. Immunotherapy,
      chemoprevention and angiogenesis. 6-10 April 2002, San Francisco, CA, USA.

PMID- 15570456
TI  - American Association for Cancer Research - 93rd Annual Meeting. Signal
      transduction. 6-10 April 2002, San Francisco, CA, USA.

PMID- 15570457
TI  - American Association for Cancer Research - 93rd Annual Meeting. Investigational
      kinase inhibitors. 6-10 April 2002, San Francisco, CA, USA.

PMID- 15570458
TI  - American Association for Cancer Research - 93rd Annual Meeting. Late-breaking
      research sessions. 6-10 April 2002, San Francisco, CA, USA.

PMID- 15570459
TI  - American Chemical Society Meeting - 223rd National Meeting. 7-11 April 2002,
      Orlando, FL, USA.

PMID- 15570460
TI  - American Chemical Society Meeting - 223rd National Meeting. New clinical
      candidates. 7-11 April 2002, Orlando, FL, USA.

PMID- 15570461
TI  - American Chemical Society Meeting - 223rd National Meeting. New drugs and
      clinical advances I. 7-11 April 2002, Orlando, FL, USA.

PMID- 15570462
TI  - American Chemical Society Meeting - 223rd National Meeting. New Drugs and
      Clinical Advances II. 7-11 April 2002, Orlando, FL, USA.

PMID- 15570463
TI  - American Chemical Society Meeting - 223rd National Meeting. Osteoporosis and mglu
      receptor modulators. 7-11 April 2002, Orlando, FL, USA.

PMID- 15570464
TI  - Use of cGMP PDE5 inhibitors in the treatment of neuropathy: a review of the
      patent literature.
AB  - In addition to the classic roles that cyclic-3',5-guanosine monophosphate (cGMP)
      is thought to play in cell function regulation, such as smooth muscle regulation,
      inhibition of platelet aggregation, visual signal conduction and neutrophil
      degranulation, it is now understood to be involved with various physiological
      functions. The tissue levels and hence activity of cGMP are determined by the
      balance between production rates from guanosine triphosphate (GTP) through the
      guanylyl cyclase pathways, and degradation to GMP by specific cyclic nucleotide
      phosphodiesterases (PDEs). PDE5 inhibitors were initially developed for a
      possible role in cardiovascular disease; their role in the treatment of erectile
      dysfunction was brought to the forefront by the development of sildenafil. The
      focus of this article is the current patent literature around the use of PDE5
      inhibitors for neuropathy. It also explores the possible hypotheses that may help
      to explain the mechanism(s) by which cGMP PDE5 inhibitors could have potential
      benefits in neuropathy.

PMID- 15570465
TI  - Recent advances in the treatment of L-DOPA-induced dyskinesia.
AB  - Parkinson's disease (PD) is a degenerative movement disorder resulting from the
      loss of dopaminergic neurons in the substantia nigra pars compacta. The most
      widely used treatment for PD is administration of the dopamine precursor L-DOPA,
      although this eventually results in uncontrolled involuntary movements
      (dyskinesia) that can be more debilitating than the underlying disease itself.
      The causes of L-DOPA-induced dyskinesia are unclear, but probably involve non
      physiological pulsatile stimulation of dopamine receptors or non-physiological
      dopamine release (eg, from serotonergic nerve terminals) in the striatum. In any
      case, this signaling leads to an imbalance in the activity of two basal ganglia
      pathways, the 'direct' and 'indirect' striatal output pathways, that are
      characterized by distinct neurochemical architectures. The wide range of
      neurotransmitter and neuromodulatory receptors present on these two striatal
      output pathways offers a huge range of potential therapeutic targets. Two main
      strategies for the treatment of dyskinesia exist: the use of drugs that can be
      given as an adjunct to L-DOPA, reducing the occurrence of dyskinesia without
      impairing its antiparkinsonian effect, or therapies with equal antiparkinsonian
      action as L-DOPA that do not elicit dyskinesia. Novel treatments for dyskinesia
      in clinical/preclinical development include A(2alpha) receptor antagonists,
      alpha(2) adrenoceptor antagonists, mu-opioid receptor antagonists and subtype
      selective NMDA antagonists. Future research strategies are likely to focus on the
      molecular mechanisms underlying the emergence of dyskinesia and may lead to the
      development of agents that can prevent or reverse the cellular changes underlying
      this phenomenon.

PMID- 15570466
TI  - Loxiglumide Rotta research.
AB  - Rotta was developing loxiglumide, a competitive cholecystokinin (CCK) antagonist,
      for potential use in the treatment of cancer, gastrointestinal disease, eating
      disorders and pancreatitis. However, by April 2002 its development for
      indications other than acute and chronic pancreatitis had been discontinued in
      favor of the D-enantiomer, dexloxiglumide [449509], which is in clinical trials
      for gastrointestinal disorders [370620]. Loxiglumide is awaiting approval in
      Japan where it is being developed for acute and chronic pancreatitis by
      Mitsubishi Pharma and Kaken Pharmaceuticals, respectively [365460], [449509]. By
      September 1999, Kaken had submitted a Japanese NDA for the intravenous
      formulation for acute pancreatitis; approval was still pending in May 2001. At
      this time, the oral formulation was still 'pre-NDA' [411053]. By February 2000,
      loxiglumide had also been filed for approval in Japan for the treatment of acute
      pancreatitis by Mitsubishi-Tokyo [365460], [371091] and was still awaiting
      approval in October 2001 [422712], [430428]. In December 2001, analysts at
      Merrill Lynch predicted launch of loxiglumide in early 2002 for acute
      pancreatitis and late 2004 for chronic pancreatitis, with sales of Yen 1 billion
      in 2003 rising to Yen 6 billion in 2006 [450719].

PMID- 15570467
TI  - PST-2238 Sigma-Tau.
AB  - Sigma-Tau is developing PST-2238, the prototype of a new class of hypertensive
      steroidal ATPase modulators, for the potential treatment of hypertension
      [169159]. Phase II trials were ongoing in early 2002 [441505].

PMID- 15570468
TI  - Climate change, growing season length, and transpiration: plant response could
      alter hydrologic regime.

PMID- 15570469
TI  - Gene expression during formation of earlywood and latewood in loblolly pine:
      expression profiles of 350 genes.
AB  - The natural variability of wood formation in trees affords opportunities to
      correlate transcript profiles with the resulting wood properties. We have used
      cDNA microarrays to study transcript abundance in developing secondary xylem of
      loblolly pine (Pinus taeda) over a growing season. The cDNAs were selected from a
      collection of 75 000 ESTs that have been sequenced and annotated
      (http://web.ahc.umn.edu/biodata/nsfpine/). Cell wall thickness and climatic data
      were related to earlywood and latewood formation at different time points during
      the growing season. Seventy-one ESTs showed preferential expression in earlywood
      or latewood, including 23 genes with no significant similarity to genes in
      GenBank. Seven genes involved in lignin synthesis were preferentially expressed
      in latewood. The studies have provided initial insights into the variation of
      expression patterns of some of the genes related to the wood formation process.

PMID- 15570470
TI  - Inhibition of phosphoinositide-specific phospholipase C results in the induction
      of pathogenesis-related genes in soybean.
AB  - The inositol 1,4,5-trisphosphate (IP3) content is decreased in soybean cells
      following infection with Pseudomonas syringae pv. glycinea (Psg). In this
      investigation, a differential display approach was applied to isolate soybean
      genes that are transcriptionally up-regulated by the inhibition of
      phosphoinositide-specific phospholipase C (PI-PLC) activity and to study if the
      transcription of those genes is altered following Psg infection. Four genes,
      transcriptionally activated following treatment with the PI-PLC-specific
      inhibitor U-73122, were cloned. Three of the four genes were induced following
      infection with Psg. The transcripts of a hydrolase homologue (GmHy) were induced
      in the incompatible but not compatible soybean-Psg interaction. The transcripts
      of a putative ascorbate oxidase gene (GmAO) were induced in both compatible and
      incompatible interactions. GmHy and GmAO may represent new classes of
      pathogenesis-related genes. In addition to these two novel genes, homologues of
      PR-10 and polygalacturonase inhibitor protein (GmPR10 and GmPGIP, respectively)
      were identified. These two genes have previously been reported as pathogenesis
      related. Transcripts of GmPR-10, but not GmPGIP, were induced in both compatible
      and incompatible soybean-Psg interactions. Induction of these genes, except for
      GmPGIP, following inhibition of PI-PLC by either the U-73122 treatment or
      bacterial infection suggests that PI-PLC may negatively regulate the expression
      of defence genes.

PMID- 15570471
TI  - Phylogeny of Veronica--a combination of molecular and chemical evidence.
AB  - A molecular phylogenetic tree of the genus Veronica, based on sequences of the
      ITS region of nuclear ribosomal DNA, provided a framework to test the use of
      iridoid chemical data in the classification of the genus. The distribution of ten
      iridoid glucosides, determined in 27 species of Veronica, supported the molecular
      results. The nine clades of the molecular tree appeared to correlate with a
      specific pattern of catalpol esters and chromosome base numbers. Some
      relationships within Veronica, previously suggested on the basis of morphological
      and karyological characters, were supported by our data. Neither the molecular,
      nor the chemical features were in favour of the classical circumscription and
      classification of the genus.

PMID- 15570472
TI  - Reduced fecundity in small populations of the rare plant Gentianopsis ciliate
      (Gentianaceae).
AB  - Habitat destruction is the main cause for the biodiversity crisis. Surviving
      populations are often fragmented, i.e., small and isolated from each other.
      Reproduction of plants in small populations is often reduced, and this has been
      attributed to inbreeding depression, reduced attractiveness for pollinators, and
      reduced habitat quality in small populations. Here we present data on the effects
      of fragmentation on the rare, self-compatible perennial herb Gentianopsis ciliata
      (Gentianaceae), a species with very small and presumably well-dispersed seeds. We
      studied the relationship between population size, plant size, and the number of
      flowers produced in 63 populations from 1996-1998. In one of the years, leaf and
      flower size and the number of seeds produced per fruit was studied in a subset of
      25 populations. Plant size, flower size, and the number of seeds per fruit and
      per plant increased with population size, whereas leaf length and the number of
      flowers per plant did not. The effects of population size on reproduction and on
      flower size remained significant if the effects were adjusted for differences in
      plant size, indicating that they could not be explained by differences in habitat
      quality. The strongly reduced reproduction in small populations may be due to
      pollination limitation, while the reduced flower size could indicate genetic
      effects.

PMID- 15570473
TI  - Blue light delays commitment to cell division in Chlamydomonas reinhardtii.
AB  - In this study, we describe the effect of red and blue light on the timing of
      commitment to cell division in Chlamydomonas reinhardtii. The time point and cell
      size after which cells can complete their cell cycle with one division round were
      determined for cultures that were exposed to various red and blue light periods.
      We show that the commitment point of cells grown in blue light is shifted to a
      later time point and a larger cell size, when compared with cells grown in red
      light. This shift was reduced when cultures were exposed to shorter blue light
      periods. Furthermore, this shift occurred only when exposure to blue light
      started before the cells attained a particular size. We conclude that the
      critical cell size for cell division, which is the cell size at which commitment
      to cell division is attained, is dependent on spectral composition.

PMID- 15570474
TI  - Nuclei of tea flowers as targets for flavanols.
AB  - The tea plant (Camellia sinensis L.) is famous for its flavanol-based
      constituents being valuable for human health. These flavanols associate with the
      nuclei of tea flowers, which is demonstrated histochemically by blue colouration
      using the selective staining reagent p-dimethylaminocinnamaldehyde (DMACA).
      Sepals, petals, stamens, pollen tubes, ovaries and ovules were studied. All these
      organs were shown to contain flavanols in vacuolar compartments, in nuclei and,
      exceptionally, also in the cytoplasm of pollen tubes. In all cells, even in those
      lacking vacuoles, the nuclei stained blue for flavanols. The extremely divergent
      development, shape and function of the diverse flower organs did not basically
      influence the nuclear flavanol association. Nevertheless, within the limits of
      this study, a few tissue-dependent differences in staining intensity were
      obvious. Interactions between epicatechin and nuclear histone proteins (histone
      sulphate) were studied by UV-VIS spectroscopic titration and by means of Mauser
      diagrams. The results show that the observed association equilibria are strongly
      dependent on pH (8.0 and 7.4) and on the buffer used (Tris, phosphate).

PMID- 15570475
TI  - Importance of N source on heat stress tolerance due to the accumulation of
      proline and quaternary ammonium compounds in tomato plants.
AB  - Proline and quaternary ammonium compounds (QAC), in addition to being N-rich, are
      known to accumulate in plants under different environmental stress conditions.
      The accumulation of N-rich compounds in plants has been shown to confer stress
      resistance. The aim of our work is two-fold: first, to study the influence of
      temperature on proline, QAC, and choline metabolism in tomato leaves; and second,
      to investigate the relationship between N source applied (NO3- or NH4+) and
      thermal stress resistance in these plants. To do this, experiments were conducted
      at three different temperatures (10 degrees C, 25 degrees C, 35 degrees C); at
      each temperature half of the plants received NO3-, and the other half received
      NH4+. At 35 degrees C the plants had the lowest biomass production with respect
      to 25 degrees C (optimal temperature) and 10 degrees C (cold stress), suggesting
      that tomato plants were most affected by heat stress. At 35 degrees C, there were
      also high levels of choline and proline due to the activation of Delta1-pyrroline
      5-carboxylate synthetase (P5CS) and ornithine aminotransferase (OAT), and
      simultaneous inhibition of proline dehydrogenase (PDH) and proline oxidase (PO).
      However, plants with NH4+ as the N source exhibited reduced growth with respect
      to the plants fed with NO3-. This is interesting because, under heat stress (35
      degrees C), biomass production, as well as proline and choline accumulation, in
      NH4+ fed plants was higher than in NO3- fed plants. From this, we concluded that
      tomato plants fed with NH4+ as the N source show higher tolerance to heat stress
      (35 degrees C) than plants fed with NO3-.

PMID- 15570476
TI  - Rejuvenation of ageing bean leaves under the effect of low-dose stressors.
AB  - The effect of low concentrations of some stress-inducing compounds like Cd, Pb,
      Ni, and Ti salts and DCMU on the senescence of chloroplasts was investigated in
      detached primary leaves of bean. After the petioles of ageing leaves had
      developed roots, these low-dose stressors stimulated chlorophyll synthesis and
      photosynthetic activity, as compared to the control, thus causing rejuvenation in
      treated leaves. The amount of photosystem I (lowest in DCMU-treated leaves) and
      light-harvesting complex II increased, while that of photosystem II decreased or
      remained unchanged. Fluorescence induction parameters indicated unchanged
      electron transport (except for DCMU treatment). CO2 fixation and, in some cases,
      starch accumulation was stimulated. In parallel, the occurrence of large
      plastoglobuli seemed to decrease in plastids of heavy metal-treated leaves. A
      cytokinin bioassay of leaf extracts confirmed the cytokinin-mediated effect of
      low-dose stressors, as the slopes of Chl and cytokinin curves were similar during
      the rejuvenation process. It is assumed that these stressors generate non
      specific alarm reactions, which involve changes in the hormonal balance by
      increasing the synthesis of cytokinins.

PMID- 15570477
TI  - The effect of fruit age on seed germinability of a heterocarpic species, Atriplex
      sagittata.
AB  - Atriplex sagittata is an annual heterocarpic plant that produces three different
      fruit types (termed A, B, and C). To examine the consequence of heterocarpy on
      germinability patterns over long time periods, we compared seed germinability of
      different fruit types that had been stored for up to 8 years. While germinability
      of non-dormant type C fruits in distilled water was high (up to 100 %) in the
      first 2 years, it rapidly decreased over time. Dormant fruit types A and B showed
      increased germinability up to 7 years, though loss of germinability was lower for
      type B than for type A fruits. Eight-year-old fruits of all types had
      significantly lower germinability than younger fruits, probably due to loss of
      viability. Heterocarpy, therefore, ensures that emergence rates for seedlings of
      A. sagittata will be maintained over relatively long periods, even in years of
      strong disturbance when all adult plants may be destroyed. The experiment further
      showed that germinability of all fruit types in high concentrations of salt, as
      compared with water treatment, changed over the course of 8 years. Whilst dormant
      types (A and B) of A. sagittata show increased germinability with age of the seed
      in water treatment, they significantly lose germinability over time with salinity
      treatment. Type C fruit was not influenced by salt in the first year, but
      germinability rapidly decreased with time. It follows that the species is able to
      germinate under high salt concentration in the first year, but this advantage
      gradually disappears.

PMID- 15570478
TI  - Stable isotope composition of organic compounds transported in the phloem of
      European beech--evaluation of different methods of phloem sap collection and
      assessment of gradients in carbon isotope composition during leaf-to-stem
      transport.
AB  - The analysis of stable isotope composition (delta13C, delta15N, delta18O) of
      phloem-transported organic matter is a useful tool for assessing short-term
      carbon and water balance of trees. A major constraint of the general application
      of this method to trees at natural field sites is that the collection of phloem
      sap with the "phloem bleeding" technique is restricted to particular species and
      plant parts. To overcome this restriction, we compared the contents (amino
      compounds and sugars) and isotope signatures (delta13C, delta15N, delta18O) of
      phloem sap directly obtained from incisions in the bark (bleeding technique) with
      phloem exudates where bark pieces were incubated in aqueous solutions (phloem
      exudation technique with and without chelating agents [EDTA, polyphosphate] in
      the initial sampling solution, which prevent blocking of sieve tubes). A
      comparable spectrum of amino compounds and sugars was detected using the
      different techniques. O, C, or N compounds in the initial sampling solution
      originating from the chelating agents always decreased precision of determination
      of the respective isotopic signatures, as indicated by higher standard deviation,
      and/or led to a significant difference of mean delta as compared to the phloem
      bleeding technique. Hence, depending on the element from which the ratio of heavy
      to light isotope is determined, compounds lacking C, N, and/or O should be used
      as chelating agents in the exudation solution. In applying the different
      techniques, delta13C of organic compounds transported in the phloem of the twig
      (exudation technique with polyphosphate as chelating agent) were compared with
      those in the phloem of the main stem (phloem bleeding technique) in order to
      assess possible differences in carbon isotope composition of phloem carbohydrates
      along the tree axis. In July, organic compounds in the stem phloem were
      significantly enriched in 13C by > 1.3 per thousand as compared to the twig
      phloem, whereas this effect was not observed in September. Correlation analysis
      between delta13C and stomatal conductance (Gs) revealed the gradient from the
      twigs to the stem observed in July may be attributed to temporal differences
      rather than to spatial differences in carbon isotope composition of sugars. As
      various authors have produced conflicting results regarding the
      enrichment/depletion of 13C in organic compounds in the leaf-to-stem transition,
      the different techniques presented in this paper can be used to provide further
      insight into fractionation processes associated with transport of C compounds
      from leaves to branches and down the main stem.

PMID- 15570479
TI  - Carbon balance in leaves of young poplar trees.
AB  - In the present study, important components of carbon metabolism of mature leaves
      of young poplar trees (Populus x canescens) were determined. Carbohydrate
      concentrations in leaves and xylem sap were quantified at five different times
      during the day and compared with photosynthetic gas exchange measurements (net
      assimilation, transpiration and rates of isoprene emission). Continuously
      measured xylem sap flow rates, with a time resolution of 15 min, were used to
      calculate diurnal balances of carbon metabolism of whole mature poplar leaves on
      different days. Loss of photosynthetically fixed carbon by isoprene emission and
      dark respiration amounted to 1% and 20%. The most abundant soluble carbohydrates
      in leaves and xylem sap were glucose, fructose and sucrose, with amounts of
      approx. 2 to 12 mmol m(-2) leaf area in leaves and about 0.2 to 15 mM in xylem
      sap. Clear diurnal patterns of carbohydrate concentration in xylem sap and
      leaves, however, were not observed. Calculations of the carbon transport rates in
      the xylem to the leaves were based on carbohydrate concentrations in xylem sap
      and xylem sap flow rates. This carbon delivery amounted to about 3 micromol C m(
      2) s(-1) during the day and approx. 1 micromol C m(-2) s(-1) at night. The data
      demonstrated that between 9 and 28 % of total carbon delivered to poplar leaves
      during 24 h resulted from xylem transport and, hence, provide a strong indication
      for a significant rate of carbon cycling within young trees.

PMID- 15570480
TI  - The impact of altitude and simulated herbivory on the growth and carbohydrate
      storage of Petasites albus.
AB  - We tested the hypothesis that higher respiratory losses caused by higher
      temperatures in the lowlands, compared to montane sites, prevent growth of the
      montane hemicryptophyte Petasites albus (Asteraceae). In addition, we tested
      whether increased levels of herbivory enhanced carbon losses at lower elevations.
      Rhizomes of Petasites albus were transplanted to a montane and a lowland site. In
      the subsequent three growing seasons the plants were artificially defoliated to
      simulate mollusc herbivory. Whereas there were no altitudinal differences in the
      leaf number per plant, the leaf area was higher at the montane site. At the
      montane site, the leaf number and leaf area decreased with increasing damage, and
      the rhizome dry weight in the third year was much higher in the undamaged plants.
      In contrast, fructan concentrations in the rhizomes that were harvested at the
      end and at the beginning of the growing seasons were generally higher at the
      lowland site. No clear defoliation effects were observed on most harvest dates.
      The results indicate that the lower altitudinal limit of Petasites albus cannot
      be explained by the negative effects of higher temperatures or more leaf damage
      by herbivores in the lowlands, either alone or in combination. An explanation
      will require consideration of other site factors such as competition and possibly
      interactions with herbivory and carbohydrate storage.

PMID- 15570481
TI  - Leaf traits and herbivory rates of tropical tree species differing in
      successional status.
AB  - We evaluated leaf characteristics and herbivory intensities for saplings of
      fifteen tropical tree species differing in their successional position. Eight
      leaf traits were selected, related to the costs of leaf display (specific leaf
      area [SLA], water content), photosynthesis (N and P concentration per unit mass),
      and herbivory defence (lignin concentration, C:N ratio). We hypothesised that
      species traits are shaped by variation in abiotic and biotic (herbivory)
      selection pressures along the successional gradient. All leaf traits varied with
      the successional position of the species. The SLA, water content and nutrient
      concentration decreased, and lignin concentration increased with the successional
      position. Herbivory damage (defined as the percentage of damage found at one
      moment in time) varied from 0.9-8.5% among the species, but was not related to
      their successional position. Herbivory damage appeared to be a poor estimator of
      the herbivory rate experienced by species, due to the confounding effect of leaf
      lifespan. Herbivory rate (defined as percentage leaf area removal per unit time)
      declined with the successional position of the species. Herbivory rate was only
      positively correlated to water content, and negatively correlated to lignin
      concentration, suggesting that herbivores select leaves based upon their
      digestibility rather than upon their nutritive value. Surprisingly, most species
      traits change linearly with succession, while resource availability (light,
      nutrients) declines exponentially with succession.

PMID- 15570482
TI  - Breeding system and floral morphometry of distylous Psychotria L. species in the
      Atlantic rain forest, SE Brazil.
AB  - General patterns of floral morphology and incompatibility mechanisms have been
      described for many distylous plants. The absence of these patterns in typically
      distylous groups, as observed especially in tropical environments, is interpreted
      as atypical distyly, or as a new reproductive strategy derived from it. Data are
      presented here on the morphological and compatibility relations between floral
      morphs of four Psychotria dimorphic species in the Atlantic rain forest in SE
      Brazil: Psychotria jasminoides, P. birotula, P. mapourioides, and P. pubigera.
      When significant differences were found, floral parts were larger in thrum
      flowers. Results of controlled crosses showed that most incompatible pollen tubes
      were arrested in the stigma, and only in a low proportion in the upper parts of
      the style. We conclude that, at the study site, the majority and most important
      morphological and mating features of typical distyly seem to be conserved in P.
      jasminoides and P. mapourioides, which presented reciprocal herkogamy, self and
      intramorph incompatibility, and a balanced morph ratio in the population. Typical
      distyly in P. birotula is supported by floral morphology, pollen tube data and
      morph ratio and, in P. pubigera, only by floral morphology and pollen tube data.

PMID- 15570483
TI  - [Proceedings of the 4th Regional Research Congress of the Bavarian Psychiatric
      and Neurologic Special Hospitals, 21-23 October 2003, Irsee]].

PMID- 15570484
TI  - [Medical controlling seen by the head of hospital].
AB  - OBJECTIVE: Medical Controlling is defined as bridge between economy,
      administration and medicine. It is concerned with structure, process and outcome
      quality of the medical capacity in hospitals. Operationalisation and precise
      description of function and procedures is far from clear until now, however.
      METHODS: Operative and strategic fields can be distinguished functionally, i. e.
      balance, payment and output-Controlling including advice of directors,
      implementation of quality management systems, benchmarking procedures and
      integrated care structures. CONCLUSIONS: According to the report presented here
      medical controlling can be regarded as essential for an ethically based economy
      in medicine. Definition and description of medical controlling seems possible now
      based on practical experiences outlined.

PMID- 15570485
TI  - [Distribution of costs in schizophrenia treatment--approaches to management and
      integration].
AB  - Intending to improve the management of psychiatric care, the service profiles,
      direct individual care costs and cost structure of a group of schizophrenic
      patients with comprehensive needs in a community health care network were
      assessed.

PMID- 15570486
TI  - [Evidence-based hospital management considering data from the psychiatric basic
      documentation system].
AB  - OBJECTIVE: The study aimed to demonstrate how data from the psychiatric basic
      documentation system (DGPPN-BADO) are able to support the hospital management in
      making evidence-based decisions. METHODS: Data from 14 327 psychiatric in
      patients in the years 1997, 1999 and 2001 were analysed. RESULTS: About 40 % of
      patients were admitted without any medical sending, 20 % were referred by a
      general practitioner and 10 % by a psychiatrist in private practice. Between 1997
      and 2001 an increase of patients with affective disorders and personality
      disorders was found. Comparing 1999 to 2001, patients showed greater deficits in
      their psychosocial capability (measured with GAF) at admission, but also at
      discharge. Outpatient aftercare was recommended to more than 80 % of in-patients,
      about 50 % by a general practitioner and about 33 % by a psychiatrist in private
      practice. 10 % of patients were cared by the own outpatient clinic. CONCLUSIONS:
      Data from the psychiatric basic documentation system could be shown as being
      relevant for evidence-based hospital management ensuring an effective and
      efficient in-patient treatment.

PMID- 15570487
TI  - [Integration of district psychiatric hospitals into the development of regional
      community psychiatry networks--the actual state. Results of a survey among
      medical directors of Bavarian district hospitals].
AB  - In this study, the medical directors of all Bavarian district psychiatric
      hospitals evaluated certain aspects of the integration of their hospitals into
      the development of regional community psychiatry networks
      ("Gemeindepsychiatrische Verbunde" - GPVs). They were asked to rate the actual
      quantity of cooperation between their hospitals and diverse community based
      services and to express their requests concerning the quality of cooperation. An
      estimation of possible advantages of the hospitals' integration in GPVs and
      expectations to future perspectives of GPV development were also investigated.
      The data were collected by a written questionnaire. The results of the survey
      indicate that a high relevance is attached to GPV: inspite of current
      heterogenous developments and inspite of existing skepticism concerning the
      feasibility of a complete GPV structure, medical directors strongly approve of
      seeing their hospitals actively engaged in the further development of community
      psychiatry networks.

PMID- 15570488
TI  - [Pathways of psychiatric in-patients].
AB  - OBJECTIVE: Pathways of psychiatric in-patients before and after their hospital
      stay should be evaluated. METHOD: Based on data of the psychiatric basic
      documentation of 4066 patients, predictors of type of referral as well as
      outpatient aftercare were analysed by means of logistic regression. RESULT: 42.5
      % of patients were admitted without any medical sending, 18.4 % by a general
      practitioner, and 9.8 % by a psychiatrist in private practice. Patients referred
      by a general practitioner suffered more frequently from affective disorders (Odds
      Ratio = 4.0) or schizophrenia (OR = 3.3), and were residents of a senior citizen
      home (OR = 3.5). Inpatients sent by a psychiatrist were more often residents of a
      sheltered home (OR = 2.8), had a present episode lasting more than three months
      (OR = 1.9) and psychopharmacological pre-treatment with atypical antipsychotics
      (OR = 1.6) or SSRI (OR = 1.8). Outpatient aftercare was recommended to 83.1 % of
      in-patients: Aftercare by a general practitioner was more frequent in patients
      with addiction disorders (OR = 2.0) and elderly patients (OR = 1.03). Referral by
      a psychiatrist in private practice (OR = 4.5) as well as schizophrenia (OR = 3.3)
      or affective disorders (OR = 2.4) led more often to an outpatient aftercare by a
      psychiatrist. CONCLUSIONS: Beside therapeutic requirements the referring person
      predicted the type of outpatient aftercare.

PMID- 15570489
TI  - [Recording and reducing coercive measures in psychiatric hospitals].
AB  - OBJECTIVE: A project of quality management funded by the German Ministry of
      Health is presented which aims at recording and reducing of coercive measures
      (seclusion, restraint, forced medication). METHOD: Since 1997, a study group for
      prevention of violence and coercion consisting of physicians, nurses and other
      psychiatric professionals from 18 psychiatric hospitals is working in Baden
      Wuerttemberg and Bayern. A common documentation of coercive measures has been
      introduced, variables of interest such as percentage of patients exposed to
      coercive measures in each principal diagnostic group of the ICD-10 have been
      defined for purposes of benchmarking. Aims of the project are 1) a complete
      documentation of all coercive measures in 12 psychiatric hospitals in a 12-month
      period and a benchmarking, taking into account structural characteristics of the
      hospitals and the respective catchment area, 2) providing a manual for a one-day
      de-escalation training for all professional groups working with psychiatric
      patients. PRELIMINARY RESULTS: A pilot study demonstrated that about 9 % of all
      admitted patients have been exposed to coercive measures in a subset of the
      participating hospitals. The variance between the hospitals was rather high.

PMID- 15570490
TI  - [German language skills among foreign psychiatric patients: influence on
      voluntariness and duration of hospital treatment].
AB  - OBJECTIVE: According to the increasing number of foreign psychiatric patients in
      the German society, the influence of their linguistic integration on treatment
      characteristics is to be investigated. METHODS: With criteria of nationality and
      German language skills, data of 6151 in-patients was collected and statistically
      analysed according to the objective. RESULTS: With statistically significant
      evidence we found a shorter average duration of hospital treatment in the group
      of linguistically badly integrated patients. In this group, involuntary hospital
      admission was significantly more frequent and release from hospital after regular
      end of treatment was significantly rarer. CONCLUSIONS: Linguistic communication
      problems may influence the cooperation and motivation in an ineffective way,
      which underlines the importance of supporting linguistic integration.

PMID- 15570491
TI  - [Prevalence of mental disorders in the out-patient clinic for environmental
      diseases (Umweltmedizinische Ambulanz) in Augsburg central hospital].
AB  - OBJECTIVE: A new concept for the out-patient clinic for environmental diseases
      (Umweltambulanz) of Augsburg central hospital was devised in July 1999. METHOD:
      By April 2003 441 patients with environment-related disorders were examined. In a
      retrospective analysis the proportion and type of mental disorders were assessed
      as well as acceptance of the psychiatric therapy recommended. RESULTS: 5 % of
      patients received a psychiatric diagnosis - in most cases a somatoform disorder.
      Half of the patients did not accept the therapy recommended. CONCLUSIONS: In
      contrast to other studies the prevalence of mental disorders is low and has
      therefore to be discussed critically.

PMID- 15570492
TI  - [Outcome of a substitution therapy program in an outpatient treatment setting of
      a psychiatric hospital].
AB  - We look at 42 opiate addicts being in substitution therapy at a certain date
      (24.9.2003) in an outpatient treatment setting of a psychiatric hospital.
      Treatment outcome is described with amount of take home, reduced delinquency,
      increased social reintegration as well as pharmacological treatment. 25 men and
      17 women, age from 20 to 49 (29) have been in our treatment between 1 to 52
      months (29). 20 of them (48 %) got an additional psychiatric medication, mostly
      antidepressants (42 %) but also neuroleptics (9,5 %). 21 patients had a drug free
      urine test (including cannabis) during the last month and could take their opiate
      medication at home. Necessity of support by social security declines from 25 %
      before to 16 % in substitution treatment. Also the need of unemployment benefit
      could be reduced from 36 % before to 26 % in treatment. Full time jobs increase
      from 31 % to 48 %, part time jobs from 3 % to 7 % in treatment.

PMID- 15570493
TI  - [Long-term psychosocial outcome of young adult inpatients after a first
      manifestation of "neurotic" symptoms].
AB  - OBJECTIVE: It is often assumed that there is a predictive relationship between
      the onset of psychiatric disorder in young adulthood and the severity of their
      course. Because the significance is rather contradictive and poorly backed by
      empirical data, we have investigated this issue by a catamnestic approach.
      METHOD: From 96 inpatients aged between 18 to 25 years with a first manifestation
      of a "psychogenetic" disorder 54 % were studied 8.6 +/- 1.5 year later. RESULT:
      In general there was a positive development as well psychopathological as social,
      although complete normalisation was not reached. CONCLUSIONS: This result is
      almost identical with catamnestic findings with comparative studies on older
      patients . Our findings do not support the concept of negative predictive value
      of first manifestation of psychogenetic disorder in early adulthood.

PMID- 15570494
TI  - [What are the differences between a year later remitted and non-remitted
      depressive patients? Results of a retrospective long-term study at the
      Bezirksklinikum Gabersee].
AB  - OBJECTIVE: The aim of this study is to investigate, whether conventionally used
      questionnaires can differentiate between depressive patients. METHOD: 52
      depressive patients were investigated by self-assessment-scales and non-self
      assessment-scales at time of admission, discharge and one year after discharge.
      The patients were subdivided in a "remitted" (n = 34) and a "non-remitted" (n =
      18) group by criteria of the ICD-10 at time of the 1-year follow-up. RESULTS: At
      the 1-year follow-up the distinction in non-remitted and remitted patients was
      confirmed by the results of the self-assessments and non-self-assessments. At
      admission non-remitted depressive patients presented themselves sicker than
      remitted patients, whereas at discharge those differences were rather apparent in
      case of the non-self-assessments. CONCLUSION: The study data show that in case of
      depressive patients self-assessment-scales and non-self-assessments-scales are
      qualified for the evaluation of a long-term outcome.

PMID- 15570495
TI  - [Predicting the job performance of schizophrenic patients].
AB  - OBJECTIVE AND METHOD: Predicting the job performance of schizophrenic patients
      after discharge from hospital has been the focus of many studies within the last
      30 years. In our own long-term study, we have started to follow-up 49
      consecutively admitted schizophrenics taking their individual return on the so
      called first employment market as primary target variable. To evaluate the
      respective predictive power, a set of different neuropsychological,
      psychopathological and psychosocial parameters was gathered in each patient. The
      data presented here are based on our first follow-up 18 months after discharge.
      RESULTS: In concordance with present literature, statistical analysis revealed
      the following variables to be of decisive significance for successful
      occupational reintegration: - presence vs. absence of negative symptoms; -
      subjective ratings by interviewer; - baseline of both psychiatric treatment and
      working tenure. CONCLUSIONS: A combination of these parameters provides a useful
      tool to assess prospectively the individual job performance of a given patient.

PMID- 15570496
TI  - [Rehospitalization rates of newly diagnosed schizophrenic patients on atypical
      neuroleptic medication].
AB  - OBJECTIVE: This research examines how successful recommended longterm medical
      treatment of schizophrenic patients is following their discharge from inpatient
      treatment by evaluating the yearly rehospitalization rates. METHODS: The sample
      consisted of 76 patients with schizophrenia who were admitted for the first time
      into Bezirkskrankenhaus Augsburg within a year. The recommended long-term medical
      treatment with conventional or atypical antipsychotics of patients after
      discharge and the one year rehospitalization rate depending on the medical
      treatment at time of discharge were examined. RESULTS: After discharge from
      hospital more than 50 % of the observed patients were treated with atypical
      antipsychotics like olanzapine, risperidone or amisupride. Only 9 % were
      discharged with conventional neuroleptics. 38 % of the 76 observed patients had
      to be readmitted. CONCLUSIONS: This research shows that the beneficial properties
      of modern atypical antipsychotics are less favourable on a lower
      rehospitalization rate than expected.

PMID- 15570497
TI  - [The mild encephalitis-hypothesis--new findings and studies].
AB  - Causes and pathogenesis of psychiatric disorders is poorly understood. Infections
      by viruses or other agents may disturb neurotransmitters and elicit behavioral
      abnormalities, and induce long lasting immune reactions, referred to as mild
      encephalitis (ME). New findings (pathology, biochemistry, imaging) in
      schizophrenia and bipolar psychoses are compatible with ME hypothesis. In Chorea
      Sydenham and PANDAS syndrome autoimmune ME seems to explain anxiety-compulsive
      hyperactivity symptoms. Add-on-therapy with Cox-II-blockers or valacyclovir
      improved acute schizophrenia, CSF filtration some cases of therapy resistant
      psychoses.

PMID- 15570498
TI  - [GABA-B-associated neuropsychiatric disorders].
AB  - OBJECTIVE: Disturbed GABA-B mediated inhibitory cortical processes are discussed
      to be involved both in schizophrenia as well as in chronic tinnitus. Transcranial
      magnetic stimulation (TMS) provides an intriguing in vivo method to investigate
      GABA-B associated aspects of cortical inhibition, thus allowing to detect disease
      related cortical inhibitory processes. METHOD: Parameters of cortical
      excitability were measured by TMS in drug-naive first-episode schizophrenic
      patients and in patients suffering from chronic tinnitus. RESULTS: The cortical
      silent period as measured by TMS indicated a dysfunctional GABA-B mediated
      cortical inhibition in both groups of patients. CONCLUSIONS: TMS offers new
      insights into the pathophysiology of neuropsychiatric disorders. Parameters of
      this technique point to changes in GABA-B associated inhibitory processes within
      thalamocortial circuits both in schizophrenia and chronic tinnitus. These data
      are in line with current models of disturbed thalamic gating in phantom
      perceptions like auditory hallucinations, chronic tinnitus and central pain.

PMID- 15570499
TI  - [Reduced contralateral preponderance of the movement-related potential during
      execution of self-initiated movements in acute prefrontal traumatic brain
      injury].
AB  - OBJECTIVES: An enhanced ipsilateral motor potential after prefrontal TBI is
      known. Our aim was to examine, whether this contributes to movement initiation or
      execution. METHODS: EEGs of 22 patients and 28 healthy controls were recorded.
      Subjects performed self-initiated movements of their right index finger. From the
      resulting movement-related potentials difference curves of corresponding left and
      right hemispheric electrodes were calculated. RESULTS: We observed significantly
      reduced difference curves at parietal electrodes P3 - P4 in the patient group
      during movement execution, but not at movement initiation. CONCLUSIONS: Our
      results point to compensatorily enhanced monitoring processes during movement
      execution following TBI. This is provided by enhanced activity of the ipsilateral
      postrolandic cortex, leading to the reduced preponderance observed in the present
      study.

PMID- 15570500
TI  - [Neurobiology of violence: results of empirical and experimental studies of
      reactive violence].
AB  - OBJECTIVE AND METHOD: An overview on neurobiological findings of violence is
      given: We present 1. neurochemical findings, 2. genetical aspects, 3.
      neuroanatomical correlates and 4. a functional network of violence. Even if
      specific neurobiological findings have not been found, impulsive violence is
      closely linked to serotonergic function and to several brain regions:
      orbitofrontal cortex, temporale lobe, amygdala. Knowing that violence has
      multifactorial determinants, a model on the neurobiological findings on violence
      is given. Thus, neurobiology is just an important part of conditions correlated
      with violence.

PMID- 15570501
TI  - [Low frequency repetitive transcranial magnetic stimulation (rTMS) for the
      treatment of chronic tinnitus--are there long-term effects?].
AB  - OBJECTIVE: Clinical, neurophysiological and neuroimaging data suggest that
      chronic tinnitus resembles neuropsychiatric syndromes characterised by focal
      brain activation. Low frequency repetitive transcranial magnetic stimulation
      (rTMS) has been proposed as an efficient method in treating brain
      hyperexcitability disorders. METHODS: Patients suffering from chronic tinnitus
      underwent a [ (18)F]deoxyglucose-PET (positron emission tomography). Fusioning of
      the individual PET scan with the structural MRI-scan (magnetic resonance imaging,
      T1, MPRAGE) revealed an increased metabolic activation in the primary auditory
      cortex as target point for rTMS. A neuronavigational system enabled the
      positioning of the figure of eight coil in relation to the target area. rTMS (110
      % motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a
      placebo controlled cross-over design. RESULTS: Following active rTMS there was a
      moderate improvement of tinnitus perception. Treatment effects lasted up to six
      months in some patients. CONCLUSIONS: Neuronavigated rTMS offers new
      possibilities in the understanding and treatment of chronic tinnitus.

PMID- 15570502
TI  - [Genetic tau-variants in patients with frontotemporal dementia].
AB  - OBJECTIVE: [corrected] To evaluate tau-associated genetic polymorphisms in
      patients with sporadic frontotemporal dementia (FTD) and healthy control
      subjects. METHOD: Tau-gene sequence of 30 patients with FTD and 30 healthy
      controls was analysed by polymerase-chain-reaction (PCR). Subsequent sequencing
      was performed to identify exonic and intronic differences between both groups.
      RESULTS: The following polypmorphisms, which are localized closely to each exon
      intron-border, have been identified: In 37 % (n = 11) of the control subjects
      three different intronic polymorphisms occur simultaneously (Intron 2, 263, C -->
      Y; Intron 3, 590, A --> R; Intron 11, 150, G --> A). In the FTD group, this
      coexistance has been observed only in 17 % (n = 5). CONCLUSIONS: In how far there
      exists a significant correlation between the newly identified triple polymorphism
      in the Tau gene and an alternated risk for FTD must be evaluated in a lager
      population. The proximity of these polymorphisms to the exon-intron border would
      facilitate functional influences on gene expression patterns. These preliminary
      results described, above potentially point to further pathogenetic factors in the
      genesis of FTD.

PMID- 15570503
TI  - [No evidence for gender-specific sharing of COMT alleles in schizophrenia].
AB  - Catechol-o-methyltransferase (COMT) plays a major role in dopamine metabolism and
      has been the object of extensive investigations in subjects affected by
      schizophrenia. Interest in the enzyme has grown in recent years following
      positive linkage findings for schizophrenia in the chromosomal region surrounding
      the COMT gene locus on 22q. In several studies, a gender-specific association of
      COMT polymorphisms with schizophrenia has been reported and has given rise to
      speculations on transmission ratio distortions. The present investigation
      addressed allelic distributions in 307 men and women with respect to the rs165599
      A > G polymorphism. No evidence was obtained for gender bias in allelic patterns,
      nor did we observe association with schizophrenia (p = 0.4). While studies
      involving same-sex siblings are lacking, gender-specific sharing of alleles does
      not appear to be a consistent feature of the COMT variant investigated.

PMID- 15570504
TI  - [Familial plaque-only Alzheimer's disease in the Rottal-Inn and Passau counties].
AB  - We describe the kindred of Alois Alzheimer's second patient, who died from plaque
      only Alzheimer's disease (AD) in 1910. There is a neuropathologically defined
      subtype of AD without or only few tangles. This plaque-only form is found in
      about 6 % of autopsied cases of AD. We recruited of AD patients with age of onset
      before 70 years from the Rottal-Inn and Passau counties in Bavaria and extended a
      kindred with familial dementia using genealogies deduced from historic parish
      records. 1247 individuals were documented genealogically. In the maternal branch
      of the kindred we documented 40 deceased individuals with possible Alzheimer's
      disease, whereas other branches of the family had no suspicious entries. We
      conclude, that there is a familial predisposition to dementia with variable age
      of onset between 36 and 80 years of age in the kindred of Johann F.

PMID- 15570505
TI  - [The role of emotions in psychopathology].
AB  - OBJECTIVE: In the present study, functional fMRI was used to test the influence
      of induced emotions on a non-affective, attention-demanding, cognitive task.
      METHOD: Twelve healthy males viewed blocks of affective pictures. Between picture
      presentation a Simon-paradigm was presented. In an alternating way blocks with
      stimulus-response compatible and incompatible trials were presented. RESULTS:
      Emotion induction differentially influenced cortical activation patterns. In
      negative mood incompatible trials in contrast to compatible trials lead to
      significant decrease of activity in emotion related brain areas like the
      amygdala, the hippocampus and the medial prefrontal cortex. CONCLUSIONS: These
      results support the hypothesis that negative emotions increase the information
      processing load and drain attentional resources. To compensate these effects
      emotion related brain areas must attenuate their activity.

PMID- 15570506
TI  - [Functional neuroanatomy of emotions].
AB  - OBJECTIVE: In the present study, functional neuroanatomy of the frontal lobe and
      limbic system could be uncovered as emotion processing neural substrates. fMRI
      was used to test the influence of induced emotions on a non-affective, attention
      demanding, cognitive task. METHOD: 6 Psychopaths versus 7 controls were analyzed
      by fMRI with a simon-paradigm after emotion induction. RESULTS: Emotion induction
      differentially influenced cortical activation patterns in emotion related brain
      areas like the amygdala and the medial prefrontal cortex. CONCLUSION: Structural
      morphological neural areas of emotion regulation in "psychopathy" show variant
      activation patterns in fMRI. The neural basis of emotional impairment could be a
      dysfunctional medial prefrontal cortex and amygdala.

PMID- 15570507
TI  - [Emotional processing in patients with a dissocial personality disorder subtype
      "psychopathy" according to PCL-R].
AB  - OBJECTIVE: Functional MRI was used to test the effects of the deficient emotional
      responsiveness of psychopathic patients on cognitive processes. METHOD: We used a
      Simon-paradigm, in which ten healthy volunteers and ten patients with a diagnosis
      of "psychopathy" (defined by Hare Psychopathy Checklist Revised) have to select
      their spatially defined responses on the basis of a nonspatial stimuli feature.
      For the emotion induction pictures from the International Affective Picture
      System (IAPS) were selected. At the beginning and intermediated by the Simon
      paradigm blocks of positive, negative or neutral pictures were presented.
      RESULTS: Patients with "psychopathy" exhibited untypical activation patterns in
      amygdala and prefrontal regions during interferences between negative or positive
      stimulations and cognitive tasks. CONCLUSIONS: These results demonstrated
      disturbed regulation of emotion-cognition-interaction in "psychopathy" according
      to PCL-R.

PMID- 15570508
TI  - [Changes in the emotional processing in depressive patients: a study with
      functional magnetoresonance tomography under the employment of pictures with
      affective contents].
AB  - OBJECTIVE: The influence of emotional contents on brain activation was examined
      using functional magnetic resonance tomography (fMRT). METHOD: Aquiring 100 EPI
      measurements of the whole brain, series of positive and negative pictures from
      the International Affective Picture System (IAPS) were shown to eight depressed
      males and to healthy controls. RESULTS: In depression, there was an
      overactivation in hippocampal area during positive stimulation, whereas an
      overactivation of amygdala, orbital and prefrontal regions was seen during
      negative stimulation. CONCLUSIONS: These results emphasize the importance of
      functional interaction between the neural network associated with emotion. We
      could show that depression is connected to dysregulation and disturbed functional
      connectivity during emotional processing.

PMID- 15570509
TI  - [Differences in cerebral glucose metabolism between frontotemporal lobar
      degeneration and Alzheimer's disease].
AB  - OBJECTIVE: To describe differences in cerebral glucose metabolism between
      frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). METHODS:
      14 patients with FTLD (7 f/7 m, mean age 60.1 years) and 14 patients with AD (7
      f/7 m, mean age 59.5 years) were examined. [18F]FDG positron emission tomography
      (PET) scans were analysed with statistical nonparametric mapping (SnPM) and
      statistical parametric mapping (SPM99). RESULTS: Significant decreases in glucose
      metabolism in FTLD compared to AD were detected in the left insula/left inferior
      frontal gyrus (Brodman area [BA]13, 45 and 47) and in the medial frontal gyrus
      bilaterally (BA10). A significant decrease in AD compared to FTLD was identified
      in the right middle temporal gyrus (BA39). CONCLUSION: Cerebral PET could be a
      promising tool to discriminate FTLD from AD.

PMID- 15570510
TI  - [Psychotherapy units in Bavarian state mental hospitals].
AB  - OBJECTIVE AND METHOD: In this paper we report about the situation of
      psychotherapeutic inpatient treatment in Bavarian state mental hospitals, based
      on data coming from surveys in those hospitals. RESULTS AND CONCLUSION: 22 State
      mental hospitals in Bavaria have 1217 beds for acute psychotherapy, proofed on
      the basis of quality criteria. More than 50 per cent of all psychotherapy beds
      are located in those hospitals.

PMID- 15570511
TI  - [The development of utilisation of psychoneurotic in-patients in hospitals for
      psychiatry and psychotherapy of the so-called "new" Federal States of Germany].
AB  - OBJECTIVE: Up to now psychotherapeutic treatment naturally is part of treatment
      strategies of mental hospitals and departments of psychiatry at general
      hospitals. Actually there is a controversial debate in this issue. The aim of
      this study was to evaluate the development of the utilization of these hospitals
      by patients with "psychogenic disorders" in the new federal states of eastern
      Germany. METHOD: We studied the changes in the utilization in hospitals of
      psychiatry and psychotherapy in Thuringia 1993 up to 1999 by patients with ICD-9
      diagnoses 300 - 1 and 306 - 9 and compared these data with these of other clinics
      in East und West Germany. RESULT: The utilization of psychotherapy patients
      increased in all hospitals. The increase in Thuringia was highest, in the other
      eastern German it was higher as in western clinics. Reasons of admissions for in
      patient psychotherapeutic treatment were suicide ideations and attempts,
      aggression against others and prepsychotic agitation. CONCLUSIONS: These results
      can be seen as a sign of a similar necessity of this care in the eastern as in
      western population under similar psychosocial conditions.

PMID- 15570512
TI  - [Treatment of patients with personality disorders in specialized units for
      psychotherapy in Bavarian psychiatric hospitals].
AB  - Data about patients with personality disorders treated in specialized
      psychotherapy units in bavarian psychiatric hospitals during the second half-year
      2001 (n = 256) were collected by a questionnaire. Diagnostic, therapeutic and
      social characteristics were registered. Treatment possibilities of the
      psychotherapeutic units und special qualifications of the staff were investigated
      as well. - RESULTS: The investigated population of personality disorders is
      mentally seriously handicapped has high rates of suicide-attempts and co
      morbidity with other mental disorders. The units for psychotherapy offer a wide
      range of different psychotherapeutic treatments. The staff is well trained in
      psychotherapeutic qualifications. These results show, that bavarian psychiatric
      hospitals play an important role in psychotherapeutic treatment of severely ill
      in-patients.

PMID- 15570513
TI  - [Unit for psychotherapy at the clinic for psychiatry and psychotherapy Bayreuth].
AB  - OBJECTIVE AND METHOD: Inpatients of "psychotherapeutic treatment units" at State
      Mental Hospitals in Bavaria are different from those treated in so-called
      psychosomatic clinics for rehabilitation, looking at additional criteria like
      psychiatric and somatic comorbidity or suicidal behaviour. RESULTS AND
      CONCLUSION: Treatment concepts and results are respectable and comparable to so
      called psychosomatic clinic. In this paper we describe the "Psychotherapy Unit"
      at the Clinic for Psychiatry and Psychotherapy Bayreuth. Depressive episode is
      the most diagnosis, with 1 to 4 comorbid psychiatric diagnosis in 82 % of all
      patients and 28 % with somatic comorbidity.

PMID- 15570514
TI  - [Integration of psychodynamic imaginative trauma therapy in a modified
      psychoanalytic concept of a inpatient psychotherapy unit].
AB  - Results of latest neurobiological trauma-research suggest that many psychic
      disorders like personality disorders with complex traumatisation in patient's
      history and co-morbidities should better be treated as posttraumatic disorders.
      This is important for any therapy planning: should a modified psychoanalytic
      approach (like TFP by Kernberg) with emphasis on interpreting the transference
      relation be preferred for patients with Borderline personality disorder or -
      diagnosing the same patients as complex posttraumatic stress disorder - a phase
      oriented trauma-specific approach. As such PITT combines psychodynamic
      understanding with hypnotherapeutic and imaginative methods. Crucial points are
      an active and supporting therapeutic relation, safety and reduction of stress,
      focus on all individual resources and use of imaginative ways for stabilization
      and later trauma-confrontation work.

PMID- 15570515
TI  - [Discharge preparation group on a psychiatric ward for acute patients: conception
      and first experience with the realization].
AB  - The installation of a discharge preparation group on a psychiatric ward for
      acutely ill patients shall enable the patient to reflect on their situation of
      life after the discharge from the hospital, to recognize individual problems and
      resources and, using multi professional help, to work out suitable ways and means
      to solve their problems. The participating patients rated this therapeutic offer
      in the whole as positive, especially because it related to their every-day-lives.
      This group led to a greater satisfaction of the patients and helped to prepare a
      more structured way of discharge from the hospital.

PMID- 15570516
TI  - [Performance improvement and compliance of schizophrenic patients participating
      in the computerbased cognitive training with X-Cog].
AB  - This study aimed to examine performance improvement and compliance of
      schizophrenic patients participating in computerbased cognitive training with X
      Cog(R). 20 patients (5 women, 15 men) with the diagnosis of schizophrenia (ICD10
      F20.X) were trained ten weeks (twice a week, duration 1h) using the software X
      Cog(R) in different wards of the Bezirksklinikum Regensburg. After the evaluation
      of the feedback given by the computer it could be demonstrated that the patients
      showed marked practice improvements. Moreover it appeared very less leisure hours
      what could be shown by an evaluation of the regularity of participation. This
      study gives first indications that X-Cog(R) could be a useful way to increase
      individual performance, motivation and especially the continuity of participation
      in a therapy of schizophrenic patients training using a computerbased cognitive
      training software.

PMID- 15570517
TI  - [Death by illegal drugs in Bavaria 1990 up to 2002].
AB  - OBJECTIVE AND METHOD: In our paper we report about drug mortality in Bavaria in
      the years 1990 up to 2002, using statistical trend tests (Spearman rho, Kendall
      tau). RESULTS: We observed an increase of deaths by illegal drugs in Bavaria as
      whole, on the other hand also decreases in different parts of the country.

PMID- 15570518
TI  - [Use of cigarettes, alcohol and drugs by adolescents--a questionnaire survey
      among 9th grade students].
AB  - INTRODUCTION: For the planning of further substance abuse prevention programs it
      is necessary to obtain data about the patterns of region-specific substance use
      in adolescents. METHOD: In 2002 a questionnaire survey on substance use among the
      9 (th) graders of all school types in the city and in the county of Regensburg
      was carried out (mean age 15,3 years, N = 1580). RESULTS: The first substance
      ever used by adolescents are cigarettes, starting at an average age of 12.2
      years. 30 % of the students are current daily smokers with 43 % fulfilling
      criteria of nicotine dependence. When used several times per week 53 % regard the
      use of spirits being very dangerous, whereas the same rate considers the danger
      of drinking wine or beer at the same frequency being rather small. The level of
      information about institutions offering help for substance abuse and dependence
      problems is being considered as poor or zero by 67 %. DISCUSSION: The primary
      prevention of smoking as early as possible should be a priority of school-based
      prevention programs. The study also reveals a deficit of information on
      substances and institutions offering help for substance abuse and dependence
      problems which should be faced in school lessons.

PMID- 15570519
TI  - [Attention-deficit hyperactivity disorder and alcohol dependence: a risk
      constellation].
AB  - INTRODUCTION: The estimated prevalence for attention-deficit hyperactivity
      disorder (ADHD) in adulthood is 2 - 6 %. Patients with a substance use disorder
      met the criteria for ADHD between 30 and 50 %. ADHD and conduct disorders are
      discussed to increase risk of developing substance abuse and increase severity of
      disorder. METHOD: We compared epidemiological and clinical characteristics and
      comorbidity in subgroups of 314 adult alcoholics of German descent with or
      without persistent symptoms of attention-deficit hyperactivity disorder (ADHD).
      Aim of the study was to identify specific pathophysiological mechanisms that
      could contribute to vulnerability, severity or complication of alcohol
      dependence. RESULTS: 21.3 % of the alcoholics fulfilled DSM-IV-criteria of ADHD
      with ongoing symptoms in adulthood and had a Wender-Utah-Rating-Scale score > 90.
      Subgroup of alcoholics with ADHD were significantly younger at age of onset of
      alcoholism (24 years versus 30 years), had a significantly higher daily alcohol
      intake (253 g versus 196 g EtOH), had significantly more social stress, lifetime
      experiences in court proceedings against them (11 versus 2 %) and suicidal
      ideation (25 versus 11 %). In the subgroup of alcoholics with ADHD 51 % fulfilled
      criteria of antisocial personality disorder. The early onset of alcoholism was
      most pronounced in this subgroup. CONCLUSION: In our sample, persistence of ADHD
      symptoms from childhood into adulthood and antisocial personality disorder
      contributes to vulnerability and morbidity of alcohol dependence with early onset
      and greater severity of disorder.

PMID- 15570520
TI  - [Attachment styles in German alcoholics with or without attention-deficit
      hyperactivity disorder (ADHD)].
AB  - INTRODUCTION: Attachment theory yields empirical constructs for development of
      human self, personality and cognition. Insecure attachment strategies were
      associated with various psychiatric disorders. METHOD: We investigated
      distribution of attachment styles in 368 adult alcoholics of German descent with
      or without persistent symptoms of attention-deficit hyperactivity disorder (ADHD)
      and in 402 healthy individuals. RESULT: Insecure attachment styles were
      significantly overrepresented compared to healthy controls. The subgroup of
      alcoholics with ADHD showed significantly more frequent enmeshed (74.1 %), the
      subgroup of alcoholics without persistent ADH-associated symptoms showed more
      frequent dismissing (35 %) attachment strategies. CONCLUSION: In our sample,
      insecure attachment styles are associated with alcoholism. The subgroup of
      alcoholics with persistent ADHD shows a specific attachment behavior that could
      contribute to different therapy response or to early onset or severity of
      alcoholism.

PMID- 15570521
TI  - [Buprenorphine or methadone for detoxification of young opioid addicts?].
AB  - OBJECTIVE: Comparison of buprenorphine vs. methadone to determine which
      medication is better for the detoxification of young opioid addicts. METHOD: 93
      consecutive opioid-dependent patients (ICD-10) from an in-patient detoxification
      unit for adolescents were investigated, of which 42 chose buprenorphine and 51
      chose methadone for detoxification. Both groups did not differ with regard to
      different sociodemographic and addiction-specific variables such as age, gender,
      initiation of drug consumption and duration of opioid intake. RESULTS: 23.5 % of
      the methadone patients and 38.1 % of the buprenorphine patients finished
      detoxification successfully, in addition the buprenorphine patients finished
      detoxification 1.62 days earlier. There was no significant difference concerning
      these items. CONCLUSION: Buprenorphine seems to be at least as effective as
      methadone for opioid withdrawal in young addicts.

PMID- 15570522
TI  - [ADHD and alcohol dependence: a common genetic predisposition?].
AB  - INTRODUCTION: Nearly 50 % of subjects with continuing symptoms of attention
      deficit hyperactivity disorder (ADHD) in adulthood show a comorbid substance use
      disorder. Both, ADHD and alcohol dependence have a high genetic load and might
      even share overlapping sources of genetic liability. METHOD: We investigated
      phenotype and 5-HTT/5-HT2c allelic characteristics in 314 alcoholics of German
      descent. RESULT: 21 % of the alcoholics fulfilled DSM-IV-criteria of ADHD with
      ongoing symptoms in adulthood. There was no significant difference in 5-HTT- or 5
      HT2c-allele distribution between alcoholics and matched controls or between
      alcoholics with or without ADHD. CONCLUSION: In our sample the functional
      relevant 5-HTT-promoter and the 5-HT2c-receptor Cys23Ser polymorphism do not
      contribute to the supposed common genetic predisposition of ADHD and alcohol
      dependence.

PMID- 15570523
TI  - [Quality of life in relatives of mentally ill people].
AB  - OBJECTIVE: The effects of mental illness on the quality of life of relatives were
      assessed with the SF-36 (Short Form-36 Health Survey). METHODS: 304 relatives of
      360 patients answered the SF-36 at hospital admission. The participant's data
      (age and gender) were randomizedly paired to data records of the German standard
      population. RESULTS: Relatives of mentally ill people judged their quality of
      life, especially their emotional well-being, significantly worse than the
      standard population. Female relatives estimated themselves as more burdened than
      male. CONCLUSIONS: By the means of SF-36 we could show that the quality of life
      in relatives of mentally ill people is clearly reduced especially in regard of
      social and psychical ranges.

PMID- 15570524
TI  - [Relatives expectations and satisfaction of psychiatric in-patients].
AB  - OBJECTIVE AND METHOD: Relatives expectations and satisfaction of psychiatric in
      patients referring the psychiatric institution should have been explored. A
      questionnaire, based upon a content analysis of interviews with relatives (n =
      32) about their expectations and satisfaction of psychiatric in-patient care was
      developed and sent to 139 relatives. The response rate was 41.7 % (n = 58).
      RESULTS: Nine of the ten most important expectations of the relatives et all
      refer to the successful and individual treatment of the patient. Referring their
      own person, relatives expect mostly an understandable and sincere enlightenment
      and information about the illness and therapy of the patient. CONCLUSIONS:
      Consumer-orientated treatment could help to make the treatment of the patient and
      consolidation accounting of the relatives more efficient and effective.

PMID- 15570525
TI  - [The situation of caregiver counselling in patients with frontotemporal lobar
      dementia in old psychiatry].
AB  - Caregiver counselling is an indispensable feature of current concepts for
      dementia treatment. Self-support groups and psychoeducative programms for
      caregivers of patients with Alzheimer's disease may reduce the burden of nursing
      and psychological strain. Specific caregiver needs from patients with
      frontotemporal lobar dementia (FTLD [frontotemporal dementia, semantic dementia,
      progressive aphasia, corticobasal degeneration]) are only partially taken into
      account. We conducted a German wide epidemiologic study which revealed that
      specific counselling for supporting relatives and caregivers of patients with
      FTLD is only fragmentary in hospital services for old age psychiatry. In most
      cases, they are referred to the local Alzheimer's disease Associations (89 %).
      Besides that, the existence of large hospital care units has significant negative
      repercussions on psychosocial supply for caregivers of patients with FTLD. To
      establish decentralized support units by these hospitals would lead to a
      significant improvement of medical and social care in this field.

PMID- 15570526
TI  - [Working with family caregivers in the psychogeriatric day hospital "Klinikum am
      Europakanal"--information, socio-emotional support and care arrangements with
      community-based services for elderly persons].
AB  - Providing support for caregivers plays an important role in the day hospital
      treatment concept. Protocols (during 15 months) of support groups for caregivers
      of patients with dementia and depression are identifying main causes of
      caregivers' burden and distress, as well as their expectations regarding day
      hospital treatment. Aims of the interventions were to support caregivers'
      positive self-concept and social competence, to inform and to train problem
      solving strategies and to develop individual care arrangements. Close cooperation
      between the day hospital and the community based services is essential for
      overall positive treatment outcomes, for integrated care arrangements after
      discharge and to ease the burden of family caregivers.

PMID- 15570527
TI  - [Analysis of comorbid psychiatric disorders in child and adolescent psychiatry
      using the standardised basic documentation].
AB  - A slightly modified version of the basic documentation of the Child and
      Adolescent Psychiatric Associations is used to record in a standardised way
      important characteristics of the patients consulting clinics in Munich and
      Regensburg. The focus of the instrument is on the diagnostic classification of
      the symptoms according to the multiaxial classification scheme. The data of 5166
      patients were analysed for frequency and type of combined psychiatric disorder.
      The results showed, that more than 60 % of the patients had more than one
      psychiatric diagnosis. The type of the comorbid disorders are discussed.

PMID- 15570528
TI  - [Group training for parents of young children with specific developmental speech
      and language disorder (SDLD)].
AB  - OBJECTIVE: Children with SDLD have a high risk of psychiatric disorder. For early
      intervention training of the parents in structured small groups is recommended.
      The aim of this pilot project is the development of a program for parents of
      german speaking children and the assessment of the acceptability by the parents.
      METHOD: The selected topics for the parent training were grouped in six moduls.
      The joint analysis of short videosequences of interactions were used as a mean
      medium. The acceptability was assessed by questionaires. RESULTS: In three groups
      with 4 - 8 participants so far completed the feedback was positive. CONCLUSIONS:
      The structured training of parents is an acceptable form also for german parents.

PMID- 15570529
TI  - [Evaluation of a group for parents of children with attention deficit
      hyperactivity disorder (ADHD)].
AB  - OBJECTIVE: The curriculum of a group for parents of children with ADHD and its
      evaluation by the participants are presented. METHOD: A questionnaire was sent to
      the participants and answered anonymously. RESULTS: With a response rate of 59 %,
      mainly positive ratings were obtained. Information on the nature of the disorder,
      on behavioural strategies and the mutual exchange with other parents and the
      therapists were considered especially helpful. CONCLUSIONS: Information on ADHD,
      behavioural interventions and the exchange among co-parents contribute
      substantially to the success of a parent training group.

PMID- 15570530
TI  - [The case of a 86-years old woman first diagnosed with Huntington's disease].
AB  - This is the rare case of a woman first diagnosed with Huntington's disease at the
      age of 86. She was first seen at our hospital in 1999 for evaluation of dementia.
      Prior to her hospitalization, she had been treated with Melperone for
      restlessness. There was no essential psychopathology other than mild dementia
      (MMSE 21). A neurological work-up identified generalized involuntary movements
      and genetic testing revealed 40 CAG repeats. Over the course of the next several
      years, the patient began to exhibit the full range of symptoms associated with
      Huntington's disease, such as severe involuntary movements and progressive
      dementia. In the end, she was bed-ridden and only able to utter a few
      unintelligible words and she succumbed to an infection in 2003 at the age of 89,
      almost 4 years after her initial diagnosis of Huntington's disease. This case
      points to the need to consider Huntington's disease as a differential diagnosis
      even when evaluating the geropsychiatric population. It is particularly important
      to isolate involuntary movements which cannot be attributed to tardive dyskinesia
      in those who have been treated with neuroleptics in the past.

PMID- 15570531
TI  - [Differentialdiagnostic problems of frontotemporal dementia--a case study].
AB  - A case study on the clinical picture of frontotemporal dementia and the
      differential diagnostic problems will be described.

PMID- 15570532
TI  - [Acute psychosis after administration of bupropion hydrochloride (Zyban)].
AB  - A 29-year old had been admitted to our institution with acute onset of
      schizophreniform psychosis after 5-day administration of sustained-release
      bupropion hydrochloride, which had been prescribed for nicotine withdrawal in a
      daily dosage of 300 mg. Examination results were found to be completely normal,
      apart from a positive drug screen for cannabis. We hypothesize that bupropion had
      induced psychotic symptoms in this patient.

PMID- 15570533
TI  - [Risk of QTc prolongation due to combination of ziprasidone and quetiapine].
AB  - BACKGROUND: Ziprasidone, a novel antipsychotic agent for the treatment of
      schizophrenia, undergoes partial metabolism by cytochrome P450 3A4. It is
      associated with moderate prolongation of QT interval, but no increased risk for
      ventricular tachyarrhythmia or sudden death was demonstrated. CASE REPORT: A 70
      year-old male was initiated on quetiapine therapy for an acute exacerbation of
      chronic schizophrenia. The baseline electrocardiogram (ECG) showed a normal QT
      interval (QTc: 417 ms). In combination therapy of quetiapine and ziprasidone the
      patient developed suddenly cardiac arrhythmia with extrasystoles and the ECG
      revealed a prolonged QTc interval of 482 ms. After breaking off treatment with
      quetiapine and reduction of ziprasidone a normalized QT interval (QTc: 428 ms)
      was measured. CONCLUSIONS: We suppose a potential of pharmacokinetic interaction
      between quetiapine and ziprasidone because of the same metabolic pathway by
      CYP3A4. Combining treatment of quetiapine and ziprasidone is therefore
      contraindicated. In addition we suggest caution using ziprasidone with any
      potential 3A4 substrate or inhibitor.

PMID- 15570534
TI  - [Diphenhydramin-overdose: anticholinergic symptoms, EEG-findings in the course
      and drug treatment of a gerontopsychiatric patient].
AB  - In this case-study the case of a 76-year old white male with the diagnosis of
      beginning dementia and psychotic symptoms, who ingested 200 mg of diphenhydramin
      in suicidal intention, is presented. After a 3 days period in an internal
      medicine ward, in which he showed only mild anticholinergic symptoms, the patient
      was transferred to the psychiatric hospital. Here he showed more severe
      anticholinergic symptoms, including EEG-changes, for a prolonged period of two
      weeks time. This case helps to show the relevance of closer observation and EEG
      controls in gerontopsychiatric patients even after the ingestion of a
      comparatively low dose of antihistaminics.

PMID- 15570535
TI  - [Erythema multiforme caused by carbamazepine].
AB  - The antiepileptic carbamazepine can reduce aggressive behaviour and can be used
      as a mood stabilizer. We present a case report of a patient suffering from
      borderline personality disorder who was treated with carbamazepine and developed
      erythema multiforme.

PMID- 15570536
TI  - [Radicular low back pain: is there a relationship between the treatment regimen
      and outcome?].
AB  - OBJECTIVE: To identify a possible relationship between the non-surgical treatment
      regimen and outcome. METHODS: In a sample of 170 patients with sciatica due to a
      herniated disk the intensity of a conservative multimodal inpatient treatment in
      a neurological department was extracted. The outcome was examined using two
      prospective cohorts (183 patients). These results were compared with published
      data from orthopaedic inpatient rehabilitation in Germany. RESULTS: The
      neurological inpatient treatment regimen was more intense than the orthopaedic
      inpatient rehabilitation, especially with regard to physiotherapy. In contrast,
      physical therapy was applied more often in orthopaedic rehabilitation. A better
      short-term outcome with regard to pain intensity was found after multimodal
      conservative treatment. CONCLUSIONS: Further studies are needed to compare
      different treatment regimens in patients with sciatica.

PMID- 15570537
TI  - [Quantification of acute muscle pain after whiplash injury using computer-aided
      pressure algesimetry].
AB  - OBJECTIVE AND METHOD: The present study utilised the PC-interactive pressure
      algesimetry to quantify cervical pain after whiplash injury. Pressure painfulness
      of the splenius and trapezius muscles was investigated in patients with an acute
      cervical syndrome after whiplash injury and compared to that of healthy subjects.
      RESULTS: Pressure painfulness of neck and shoulder muscles was significantly
      increased in whiplash patients. The trapezius muscles were more painful left than
      right, probably due to the seat belt position. CONCLUSIONS: The computer
      interactive pressure algesimetry enables a standardised, rater-independent
      quantification of cervical pain due to whiplash injury.

PMID- 15570538
TI  - [Diurnal variation of pain perception and heart rate in the human tourniquet pain
      model in healthy volunteers].
AB  - The diurnal variation of pain threshold was studied in 13 healthy volunteers
      (age: 21 - 27 ys) using the tourniquet pain model. A tourniquet was inflated
      above systolic blood pressure for 1 minute and pain scores and heart rate were
      recorded at 0.5, 1.0, 1.5 and 2.0 minutes. The test was repeated during a study
      day at 6.00 h, 12.00 h, 18.00 h and 24.00 h. Significant differences of pain
      scores between clocktimes were found 1 minutes after inflation and after 1.5
      minutes with regard to heart rate. Generally, the highest pain scores were found
      at 24.00 h.

PMID- 15570539
TI  - [Antipsychotics and memory functions in schizophrenic patients].
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of antipsychotics on
      memory functions in schizophrenic patients under clinical routine conditions.
      METHOD: Schizophrenic patients (n = 111) before discharge to outpatient treatment
      were evaluated on verbal memory function. Data were analyzed according to
      pharmacological treatment controlling for age. RESULTS: We observed that
      treatment with atypical antipsychotics (n = 80) compared with conventional
      neuroleptics (n = 31) was significantly associated with a more favorable effect
      on memory function. In short-term- and working-memory and retention a clear
      advantage of atypical antipsychotics could be seen. CONCLUSIONS: Results from
      this study suggest that even under clinical routine conditions atypical
      antipsychotics have an advantage on memory function when compared with
      conventional antipsychotics.

PMID- 15570540
TI  - [Influences of second generation antipsychotics on the course of schizophrenia].
AB  - Although there were multiple initiatives to modify course and outcome of
      schizophrenia by optimizing present psychopharmacologic strategies many unsolved
      problems still exist. There is no doubt that first generation antipsychotics
      reduce positive symptoms of psychosis but the impact on negative symptoms or
      disturbances of affect or cognition remains very poor. In contrast second
      generation antipsychotics show significantly a better tolerability, especially
      less extrapyramidal side effects. However, they may initiate strong individual
      side effects. This article reflects advantages and disadvantages of modern
      antipsychotics on the course of schizophrenia.

PMID- 15570541
TI  - [Alterations of gait parameters under external cueing in schizophrenic patients:
      a switch study].
AB  - Schizophrenic disorders as well as neuroleptic treatment can affect locomotion.
      The study assessed the influence of neuroleptic treatment on externally triggered
      gait on a treadmill at three different velocities via ultrasonic topometric gait
      analysis. Spatial and temporal gait parameters were assessed in two groups of
      schizophrenic patients either under treatment with conventional neuroleptics (n =
      12) or without neuroleptic treatment (n = 10) and re-assessed after treatment
      change to the atypical neuroleptic olanzapine in a repeated measures design.
      After switch from conventional neuroleptics to olanzapine patients showed an
      increase of step length and decrease of cadence at the low (p </= 0.01) and the
      intermediately low treadmill velocity (p </= 0.05), whereas the parameters
      remained stable at the normal gait velocity. Significant differences between the
      untreated state and treatment with olanzapine were not detectable. We conclude
      that conventional neuroleptic treatment impairs the regulation of gait parameters
      and that this effect can be reversed at slow gait velocities by external
      stimulation via treadmill walking.

PMID- 15570542
TI  - [Incidence of rigor during treatment with flupentixol decanoate in comparison to
      risperidone].
AB  - STUDY OBJECTIVE: We investigated as to whether dosedependent extrapyramidal
      tolerance of Flupentixol decanoate is inferior to that of Risperidone. METHOD:
      143 Risperidone and 177 Flupentixol decanoate treated patients were consecutively
      entered into this non - randomized open study and assessed with the Simpson-Angus
      Scale regarding presence of rigor. Treatment comparisons of rigor frequency was
      done by Kaplan-Meier analysis. RESULTS: The risk of rigor increased with dose on
      both treatments. EPMS-risk was not increased under treatment with Flupentixol
      decanoate (mean dose 35.06 +/- 19.7 mg/2 weeks) compared to Risperidone (mean
      daily dose: 5.2 +/- 2.5 mg/kg) when comparable weight standardized Haloperidol
      equivalence doses (WHE) were used. CONCLUSION: This study offers limited evidence
      for methodological reasons. Yet, results do not support the view that EPS are
      more frequent on Flupentixol decanoate than on Risperidone when doses are
      comparable.

PMID- 15570543
TI  - [Psychopharmacotherapy in psychiatric nursing homes: myth and reality].
AB  - Isolation and tranquillization are often said to be the main concerns of
      psychiatric nursing homes. However, little is known about nowadays daily
      practice. The aim of our study was to investigate the present mode of
      psychopharmacological treatment in nursing homes serviced by our psychiatric
      ambulance. For that purpose, a standardized questionnaire was applied. There was
      slight trend in favour of atypical antipsychotics (49 %) as opposed to
      conventional neuroleptics (46 %). In 18 % of the patients, a combination of both
      atypical and conventional antipsychotics was administered, while only in 5% two
      or more conventional neuroleptics were given at the same time. Taken together, we
      could assure a modern psychopharmacotherapy trying to optimize the individual
      level of cognitive and psychosocial functioning.

PMID- 15570544
TI  - [Drug monitoring of antipsychotics and antidepressants during acute admission in
      a psychiatric state hospital in Germany].
AB  - In the treatment of affective and schizophrenic psychosis, modern atypical
      antipsychotic agents and newer antidepressive agents recently have increasingly
      been used. In this prospective naturalistic study, patients were examined who had
      previously been treated psychopharmaceutically for a schizophrenic (n = 52) or
      depressive (n = 38) disorder and were readmitted in a psychiatric emergency
      clinic. While Serum levels were examined major interest was to find out
      similarities or differences in the drug compliance of schizophrenic and
      depressive patients before rehospitalization.

PMID- 15570545
TI  - [Determining serum concentrations of the modern antipsychotic quetiapin: clinical
      relevance in therapeutic drug monitoring].
AB  - OBJECTIVE: The results concerning therapeutic drug monitoring of Quetiapin
      concentration in 152 in-patients will be presented. METHOD: In addition to
      measuring the serum concentration of Quetiapin standardized patient data were
      collected and the clinical history assessed by the Brief Psychiatric Rating Scale
      (BPRS). RESULTS: A significant positive correlation of the serum concentration
      and the daily dosage was found. Co-medication with the CYP 3A4 inhibitor
      Nefazodon was associated with an increase in the serum concentration without any
      adverse interactions occurring. CONCLUSION: While a correlation of dosage and
      effect could be shown with Quetiapin, inter- and intraindividual differences
      could be observed. Drug monitoring therefore seems useful in clinical setting and
      is recommended.

PMID- 15570546
TI  - [QTc-interval prolongation in therapy with atypical antipsychotics--results of an
      open, non-randomized survey].
AB  - The introduction of Ziprasidone stimulated discussion about frequency and
      importance of QTc-interval prolongations with antipsychotic therapy. In an open
      non-randomized study we collected data about QTc-interval, electrolytes, vital
      parameters and associated clinical symptoms in patients treated with atypical
      antipsychotics. 33 patients were scanned and some moderate QTc-interval
      prolongations but no clinical events were seen. Due to scarcity of such events
      existing data should be completed by large scale clinical studies and by
      registration of severe QTc-interval prolongations and torsades de pointes in
      central drug monitoring systems.

PMID- 15570547
TI  - [Management of the atypical antipsychotic olanzapine in a clinical environment
      with particular regard to therapeutic drug monitoring (TDM) in a German State
      hospital].
AB  - OBJECTIVE: Therapeutic drug monitoring (TDM) has been established at BKH Augsburg
      (psychiatric district hospital) since January 2001. According to Olanzapine
      product information the following illustration shows the evaluation (n = 216) of
      various parameters of the TDM requirements of Olanzapine. METHODS: Items examined
      include "classification according to diagnoses", "reason for requirement",
      "severity of disease", "therapeutic effect" and "side-effects". In addition,
      serum concentration, daily dosage, clinical assessment (Brief Psychiatric Rating
      Scale), age, height and weight of patients will be presented. RESULTS: Clearly
      sick patients, 52 % of them between 20 and 30 years old, were less compliant and
      achieved only a moderate therapeutic effect. CONCLUSIONS: TDM is mainly assessed
      to control compliance. However, more specific and more personalized TDM would be
      more useful.

PMID- 15570548
TI  - [Assessment and outcome of perinatal and neonatal care in North Rhine area].
AB  - The objective of the quality assurance program "Perinatalerhebung" and
      "Neonatalerhebung" is to ameliorate the perinatal and neonatal care in German
      hospitals. Standardised data defined by a team of experts in the early seventies
      are documented for more than 20 years in the North Rhine area. The documentation
      of more than 1.6 million deliveries created a data pool that served as a
      thesaurus for the improvement of medical care in obstetrical units. The same has
      been achieved for neonatal care on the documentation basis of more than 168,000
      newborn infants admitted to a neonatal department. The results show that the
      approach to evaluate continuously the data monitored enables improvement in care.
      The support given is the anonymous collection of the documentation sheets/data
      sets and their evaluation by an expert committee. The results show that
      obstetrical management changed and the measurable results improved demonstrably.
      The efforts seem to be worthwhile in view of the fact that less than 1 % of the
      total cost of care has been spent for this project.

PMID- 15570549
TI  - [Current state of uterine artery embolization for treating symptomatic leiomyomas
      of the uterus].
AB  - A number of new approaches in treating symptomatic leiomyomas of the Uterus have
      been introduced in recent years. Only little scientific data is available an
      percutaneous or laparoscopic myolysis using focussed ultrasound, laser, or
      coagulation guided by magnetic resonance imaging or an laparoscopic ligation of
      the uterine vessels by means of bipolar coagulation or clipping. Established
      therapeutic options are limited by a number of disadvantages, except for total
      laparoscopic hysterectomy with morcellation. The latter is a minimally invasive
      procedure that spares important pelvic structures and thereby reduces the risk of
      prolapse and is associated with rapid recovery of the patients. Another minimally
      invasive therapeutic approach with preservation of the uterus is transarterial
      catheter embolization of uterine leiomyomas in which the vessels supplying the
      leiomyomas, in particular the branches of the uterine artery, are partly occluded
      by injection of synthetic (polyvinyl) beads. Uterine artery embolization has
      since developed into a good alternative to other therapeutic options. Studies
      report cure rates ranging from 77-93 %.

PMID- 15570550
TI  - [Improvement of life-quality after surgery for breast reduction].
AB  - PURPOSE: Within this study the improvement of life quality in patients after
      surgery for breast reduction should be evaluated. MATERIAL AND METHOD: In total
      70 patients, who had undergone an operation for breast reduction in the
      University Women's Hospital of Heidelberg from May 1998-June 2000, were chosen
      for this study. They were invited to an interview with three different
      standardized questionnaires concerning life quality. In total the questionnaires
      of 37 patients could be evaluated. They were about 12 months after operation.
      RESULTS: It could be shown, that all patients had a significant improvement of
      their functional symptoms, the main part of them were totally free of symptoms
      after the operation. Most patients felt more female than before. They regarded
      themselves as more active, productive and sociable. This resulted in an improved
      self-confidence. In both groups the improvement was based mostly on a release of
      their functional complaints such as pain in th back or in the shoulders, but also
      on the psychological relief of the physical shame. The reduction of the breast
      masses, which were before well hidden by clothes, led to an improved self
      confidence and self-assurance. CONCLUSION: Either women, who underwent the
      operation due to medical reasons, as well as women, who had mainly esthetic
      reasons for the operation, reach an improvement of life quality after surgery.
      The reached satisfaction of the patients and the improvement of life quality were
      absolutely independent from the weight of the resected tissue.

PMID- 15570551
TI  - [Cellular immunotherapy in advanced carcinoma of the breast by means of tumour
      antigen-specific autologous T-memory bone marrow cells as a phase I study].

PMID- 15570552
TI  - [Optimisation of possible success in an IVF program].
AB  - The success of an IVF (in vitro fertilisation) programme is mainly dependent an
      the quality of the IVF laboratory. Beside this the quality of ovarian stimulation
      play another, but not as important role. In the 4 (th) quarter of 2003 we have
      changed the culture media for oocytes and embryos in the IVF laboratory of
      ENDOKRINOLOGIKUM Hamburg from simple to complex media (G-1 version 3). As protein
      source we used HSA-solution. Before embryo transfer equilibration for 1 hour in
      EmbryoGlue was performed, which contains hyaluran. Hyaluran is said to improve
      implantation rates by different ways. The media were bought from Vitrolife
      Schweden AB (Kungsbacka, Schweden) via a German distributor. These data were
      compared to those of two previous 3-month-periods (3rd quarter 2003 und 4th
      quarter 2002). The study design was prospective, with two historical control
      groups. In the three study periods 255, 343 and 503 patients were treated by
      either conventional IVF or ICSI (intracytoplasmic sperm injection). The cohorts
      were comparable regarding their anamnestic data. The number of patients treated
      which the GnRH antagonist cetrorelix (Cetrotide) significantly increased from
      24.9 % to 49.5 % and 60.9 %. Under this protocol significantly less oocytes were
      retrieved (10.23 vs. 8.73 vs. 8.88), leading to slightly less embryos (1.94 vs.
      1.91 vs. 1.85, not significant, n. s.). The cumulative embryo score significantly
      decreased from 28.58 to 24.10. It was significantly higher in the study cohort as
      compared to the two control cohorts (32.44). The clinical pregnancy rate
      significantly increased to 25.29 % in the study cohort as compared to the two
      historical control cohorts (15.02 % and 18.75 %). We could achieve a significant
      improvement in the success rates of our IVF program by switch from simple to more
      complex culture media in the IVF laboratory. The use of the GnRH antagonist
      protocol with cetrorelix (Cetrotide) lead to more comfort to the patients but did
      not influence the results.

PMID- 15570553
TI  - [Investigations on regulation of HCG by cortisol (prednisolon) in trophoblast
      cells in vitro].
AB  - OBJECTIVE: Trophoblast cells synthesize a variety of hormones, in which hCG plays
      a major role. On the strength of special enzymes they are capable of catalyzing
      the reaction cortisol <--> cortisone. In vitro experiments showed the influence
      on ACTH- and cortisol secretion by CRH, ACTH and prednisolon. In this study we
      describe the influence of cortisol (prednisolon) on hCG production of trophoblast
      cells in vitro. MATERIAL AND METHODS: Trophoblast cells were prepared from human
      term placentae by standard trypsin-DNAse dispersion of villous tissue followed by
      a percoll gradient centrifugation step. After adjusting the cell suspension to a
      defined cell concentration of 1 x 10 (6) cells/ml cells were cultivated. The
      addition of prednisolon followed every eight hours. The samples were collected
      after 24 hours for a total of 96 hours also from unstimulated cultures. Culture
      supernatants were assayed for hCG by enzyme-immunometric methods. RESULTS: The
      addition of prednisolon (50 microg/ml) stimulates the concentration of hCG in a
      time-depending manner. CONCLUSIONS: The trophoblast cell shows an increase in the
      concentration of hCG after stimulation with cortisol. For the first time an
      influence of cortisol (prednisolon) on hCG production could be demonstrated in
      cultured trophoblast cells.

PMID- 15570554
TI  - [Laparoscopic-assisted replacement of inverted puerperal uterus: a case report
      and brief review of the literature].
AB  - Chronic inversion of the uterus is a serious obstetric complication often
      requiring laparotomy as manual replacement alone usually fails. We report on the
      successful laparoscopic-assisted replacement of a chronically inverted puerperal
      uterus on the 11th day post partum. The scientific literature back to the 19th
      century is briefly discussed.

PMID- 15570555
TI  - Systematic evaluation of genetic variation at the androgen receptor locus and
      risk of prostate cancer in a multiethnic cohort study.
AB  - Repeat length of the CAG microsatellite polymorphism in exon 1 of the androgen
      receptor (AR) gene has been associated with risk of prostate cancer in humans.
      This association has been the focus of >20 primary epidemiological publications
      and multiple review articles, but a consistent and reproducible association has
      yet to be confirmed. We systematically addressed possible causes of false
      negative and false-positive association in >4,000 individuals from a multiethnic,
      prospective cohort study of prostate cancer, comprehensively studying genetic
      variation by microsatellite genotyping, direct resequencing of exons in advanced
      cancer cases, and haplotype analysis across the 180-kb AR genomic locus. These
      data failed to confirm that common genetic variation in the AR gene locus
      influences risk of prostate cancer. A systematic approach that assesses both
      coding and noncoding genetic variation in large and diverse patient samples can
      help clarify hypotheses about association between genetic variants and disease.

PMID- 15570556
TI  - Molecular methods to distinguish reactive and neoplastic lymphocyte expansions
      and their importance in transitional neoplastic states.
AB  - Although lymphoma and leukemia usually can be diagnosed by routine cytology and
      histology, some cases present a diagnostic challenge for pathologists and
      clinicians. Often the dilemma lies in determining whether a population of
      lymphocytes is reactive or neoplastic. We review currently available methods for
      analyzing lymphocyte populations by immunophenotyping and by identifying clonally
      rearranged immunoglobulin and T-cell receptor genes and discuss how these tests
      can be used to clarify such diagnostic dilemmas. We also describe the detection
      of chromosomal abnormalities and methods on the horizon, such as gene expression
      profiling, to identify diagnostically useful oncogenes. Finally, we review the
      emerging concept of transitional neoplastic states, in which reactive lymphocytes
      transform to neoplastic lymphocytes in the presence of continued antigenic
      stimulation, such as that caused by infection with Helicobacter pylori. The
      existence of transitional neoplastic states underscores the need for an array of
      molecular diagnostic tools that would improve our ability to characterize
      lymphocyte populations in human and animal patients and enhance early detection
      of neoplastic lymphocytes such that eradication of the infectious or inflammatory
      stimulus could lead to cure.

PMID- 15570557
TI  - Evaluation of a chromogenic assay to measure the factor Xa inhibitory activity of
      unfractionated heparin in canine plasma.
AB  - BACKGROUND: Unfractionated heparin (UFH) has a complex pharmacologic profile that
      necessitates patient monitoring to prevent inadequate anticoagulation or
      overdosage and hemorrhage. Factor Xa inhibitory assays (to measure anti-Xa
      activity) are used to adjust UFH dosage and define safe and effective regimens
      for specific thrombotic disorders in humans. OBJECTIVE: In this study, the
      accuracy, linearity, and clinical utility of a chromogenic assay were assessed
      for monitoring UFH anti-Xa activity in canine plasma samples. METHODS: A
      commercial assay (Rotachrom Heparin, Diagnostica Stago, Parsippany, NJ, USA) was
      used to measure anti-Xa activity in canine plasma samples spiked with different
      concentrations of UFH. Background absorbance and assay linearity were compared
      for canine and human plasmas. Percentage recovery of UFH anti-Xa activity and
      intra- and interassay imprecisions were investigated by multiple measurements of
      canine plasma to which known amounts of UFH were added. The spiked plasma samples
      also were used to determine the heparin sensitivity of an activated partial
      thromboplastin time (aPTT) test. RESULTS: Canine plasma samples were assayed at a
      higher dilution than were human plasma samples (3:8 versus 4:8) to eliminate
      higher background anti-Xa activity in canine plasma. Using this modification, the
      recovery of anti-Xa activity in canine plasma was linear (R2 > .9) at
      concentrations of 0 - 0.75 U/mL UFH. Intra- and interassay imprecisions for
      plasma samples containing 0.5 U/mL UFH were <10%, whereas samples containing 0.25
      U/mL UFH had imprecisions of 13% and 24%, respectively. The anti-Xa activity
      range of 0.5 - 0.75 U/mL caused prolongation of aPTTs to 1.5 - 2.5 times the
      assay mean. CONCLUSION: Plasma anti-Xa activity of dogs treated with UFH can be
      accurately monitored using this commercially available chromogenic assay.

PMID- 15570558
TI  - Serum alkaline phosphatase isoenzyme profiles in phenobarbital-treated epileptic
      dogs.
AB  - BACKGROUND: Serum total alkaline phosphatase (AP) activity commonly is high in
      dogs receiving phenobarbital. Specific isoenzymes responsible for this increase
      are not well documented. OBJECTIVES: The purposes of this study were 1) to
      qualitatively and quantitatively describe serum AP isoenzymes in phenobarbital
      treated dogs and 2) to monitor changes in serum AP isoenzyme activities
      associated with phenobarbital treatment over time. METHODS: Serum AP isoenzyme
      activities were determined in a cross-sectional study of 29 dogs receiving
      phenobarbital (duration of treatment 2 months to 6.5 years). Additionally, in a
      prospective study of 23 dogs, serum AP isoenzyme activities were determined
      before and 3 weeks, 6 months, and 12 months after the start of phenobarbital
      treatment. Isoenzyme activities were quantitatively determined using wheat germ
      lectin precipitation and levamisole inhibition, and qualitatively (ie, present or
      absent) evaluated using cellulose acetate affinity electrophoresis. RESULTS: In
      phenobarbital-treated dogs with high serum total AP activity in the cross
      sectional study, the increase was due predominantly to increased activities of
      the corticosteroid-induced (C-AP) and liver (L-AP) isoenzymes. Prospectively,
      serum total AP and L-AP activities were significantly higher at 3 weeks, 6
      months, and 12 months after the start of phenobarbital treatment compared with
      pretreatment values. Serum C-AP and bone isoenzyme (B-AP) activities were
      significantly higher after 6 and 12 months of treatment. B-AP accounted for only
      a small amount of the total AP activity. No unusual or previously unidentified AP
      isoenzymes were identified. CONCLUSIONS: Phenobarbital treatment was associated
      with increased C-AP and L-AP isoenzyme activities and with a minor increase in B
      AP activity. No unique "phenobarbital-induced" isoenzyme was identified.
      Isoenzyme analysis does not appear to be useful for differentiating between high
      serum total AP due to phenobarbital therapy and other causes.

PMID- 15570559
TI  - Molecular cloning and expression of canine hepcidin.
AB  - BACKGROUND: Hepcidin is a recently identified acute phase protein with
      antimicrobial and iron regulatory functions. It has been suggested that hepcidin
      may be the key mediator of anemia of chronic disease. Our research group is
      interested in developing a diagnostic assay to measure hepcidin in dogs.
      OBJECTIVES: The objectives of this study were to clone and sequence the canine
      hepcidin gene and to gather preliminary data about tissue expression of hepcidin
      in dogs. METHODS: RNA was extracted from fresh canine liver tissue and cDNA was
      generated and amplified. Standard reverse transcription polymerase chain reaction
      techniques were used with degenerate primers based on sequence homology between
      several other species. The amino acid (AA) sequence was compared with known
      sequences in other species. Tissue expression of canine hepcidin was determined
      by Western blot. RESULTS: The canine hepcidin cDNA sequence encoded a highly
      conserved protein of 85 AAs with 8 cysteine residues at the C-terminal end. This
      protein was likely the precursor form (pro-hepcidin) of a smaller secreted
      peptide. Phylogenetic analysis showed that human hepcidin was more homologous
      with canine than with rodent hepcidin. In dogs, as in people, hepcidin was
      expressed most strongly in the liver. Western blotting showed a clear band of
      approximately 9 kDa, consistent with pro-hepcidin. Weak expression was also
      detected in canine kidney and lung tissues. CONCLUSION: The results of this study
      establish the basis for future investigation involving canine hepcidin and
      suggest that the dog may be a suitable model for studying the role of hepcidin in
      human health and disease.

PMID- 15570560
TI  - Determination of free and total cyst(e)ine in plasma of dogs and cats.
AB  - BACKGROUND: In human blood, the amino acid cysteine forms disulfide bonds with
      itself and with other sulfhydryl compounds in their free form and with
      sulfhydryls in protein. Protein-bound cysteine is lost when plasma proteins are
      removed before amino acid analysis. OBJECTIVE: The purpose of this study was to
      assess the time course and extent of cyst(e)ine (cysteine + half-cystine) loss in
      dog and cat plasma. METHODS: An equal volume of 6% sulfosalicylic acid was added
      to plasma aliquots at 0, 2, 4, 10, 16, 24, 36, 48, 60, and 72 hours after
      separation of blood cells. Tris-2-carboxyethyl-phosphine hydrochloride (TCEP -
      HCl), a reducing agent, was used to regenerate total plasma cyst(e)ine after 3
      months of sample storage (-20 degrees C). RESULTS: Initial free cyst(e)ine
      concentrations (mean +/- SEM) were higher in canine plasma (77 +/- 4 micromol/L)
      than in feline plasma (37 +/- 3 micromol/L). Free plasma cyst(e)ine
      concentrations in dogs and cats decreased after first-order kinetics, with a half
      life of 23 and 69 hours, respectively. Total plasma cysteine after TCEP - HCl
      treatment was similar for dogs (290 micromol/L) and cats (296 micromol/L), but
      the percentage of free cysteine was higher (P = .02) in dogs (27%) than in cats
      (13%). Over half of the cyst(e)ine, homocysteine, cysteinylglycine, and
      glutathione were bound in vivo to plasma proteins. CONCLUSION: These results
      emphasize the importance of removing plasma proteins within 1 hour after blood
      collection for reliable assay of free plasma cyst(e)ine.

PMID- 15570561
TI  - Stomatocytosis in 7 related Standard Schnauzers.
AB  - BACKGROUND: Hereditary canine stomatocytosis has been described in purebred
      Alaskan Malamutes, Drentse Patrijshonds, and Miniature Schnauzers. In humans,
      hereditary stomatocytosis is a heterogeneous group of congenital disorders
      characterized by the presence of stomatocytes in blood, increased osmotic
      fragility, and frequently, hemolytic anemia. OBJECTIVE: Our objective was to
      describe hematologic findings and RBC characteristics in 7 closely related
      Standard Schnauzers with stomatocytosis. METHODS: The following parameters were
      measured using an automated analyzer: HCT, RBC, hemoglobin (Hb) concentration,
      MCV, MCH, MCHC, red cell distribution width (RDW), WBC, platelet count, mean
      platelet volume (MPV), thrombocrit (PCT), and platelet distribution width (PDW).
      Differential leukocyte count, platelet estimate, reticulocyte count, and the
      percentage of stomatocytes in blood films were microscopically evaluated. An
      osmotic fragility test of RBCs and measurement of intracellular Na+, K+, and 2,3
      diphosphoglycerate (2,3-DPG) concentrations were also performed. RESULTS: The
      affected dogs had macrocytosis (80.0 +/- 4.2 fL, reference interval 60-76 fL),
      decreased MCHC (29.3 +/- 0.8 g/dL, reference interval 32-39 g/dL), slightly
      increased RDW (17.3 +/- 0.4%, reference interval 12-16%), and an increased
      reticulocyte count (1.55 +/- 0.77%, reference interval <1%). The percentage of
      stomatocytes in blood films varied from 0.6 to 18.9% of all RBCs. Erythrocyte
      osmotic fragility and intracellular Na+ (138.1 +/- 3.2 mmol/L; controls 99 +/-
      6.1 mmol/L), K+ (8.1 +/- 0.8 mmol/L; controls 6.1 +/- 0.5 mmol/L), and 2,3-DPG
      (21.9 +/- 2.0 micromol/g Hb; controls: 14.6 +/- 3.3 micromol/g Hb) concentrations
      were increased in dogs with stomatocytosis. CONCLUSIONS: Hematologic findings and
      the metabolic defects in RBCs in these Standard Schnauzers were consistent with a
      diagnosis of stomatocytosis. Parentage analysis suggests that stomatocytosis in
      Standard Schnauzers may have a hereditary component.

PMID- 15570562
TI  - Frequencies of feline blood types in northern Portugal.
AB  - The frequencies of feline blood types in northern Portugal were studied by
      surveying 185 pedigreed and nonpedigreed cats. Blood typing was performed by the
      traditional tube method. As a single group, the majority of cats were type A
      (90.3%), 3.8% were type B, and 5.9% were type AB. Among pedigreed cats, 19 were
      Siamese and 7 were Persian; all but 1 were type A. Among nonpedigreed cats, 89.3%
      were type A, 4.4% were type B, and 6.3% were type AB.

PMID- 15570563
TI  - Artifactual hypoglycemia associated with hemotrophic mycoplasma infection in a
      lamb.
AB  - BACKGROUND: A 35-day-old male lamb with Mycoplasma ovis infection (previously
      Eperythrozoon ovis) was evaluated because of severe hypoglycemia (serum glucose 4
      mg/dL, Hitachi 704 automated chemistry analyzer) inconsistent with the animal's
      condition. Whole blood glucose concentration measured with a glucometer was 74
      mg/dL. OBJECTIVE: The purpose of this study was to investigate this discrepancy
      through in vitro evaluation of the patient's blood. METHODS: Blood was incubated
      alone, with increasing concentrations of plasma, or with equine serum of known
      glucose concentration for 0, 15, 30, and 60 minutes at room temperature; end
      point glucose concentrations were compared with blood from a control sheep
      handled similarly. RESULTS: A rapid decline in glucose concentration was observed
      in heparinized or EDTA anticoagulated whole blood from the infected lamb
      incubated alone or with the equine serum. Glucose concentrations in incubated
      samples from a control sheep remained stable. Incubation of increasing
      concentrations of heparinized blood with autologous plasma resulted in decreased
      glucose concentrations in patient, but not control, blood. As parasitemia
      decreased after treatment, serum glucose concentration increased, serum lactate
      concentration decreased, and in vitro glucose concentration stabilized.
      CONCLUSIONS: These findings are consistent with parasite-associated in vitro
      glucose consumption. An increase in the lamb's plasma glucose concentration
      associated with reduction of parasite load suggested excess glucose consumption
      also may have occurred in vivo.

PMID- 15570564
TI  - Mixed Ehrlichia canis, Hepatozoon canis, and presumptive Anaplasma
      phagocytophilum infection in a dog.
AB  - A 5-month-old, female, mongrel dog was admitted to the Clinic of Companion Animal
      Medicine, Aristotle University of Thessaloniki, Greece, with depression,
      anorexia, fever, peripheral lymphadenopathy, splenomegaly, oculonasal discharge,
      nonregenerative anemia, and mild thrombocytopenia. Cytology of Giemsa-stained
      buffy coat, bone marrow, and lymph node aspiration smears revealed numerous
      morulae in mononuclear leukocytes and in neutrophils, and Hepatozoon canis
      gamonts in neutrophils. The dog was seropositive to Ehrlichia canis
      (immunofluorescence assay [IFA]) and Hepatozoon canis (ELISA) but not to
      Anaplasma phagocytophilum (IFA). A nested polymerase chain reaction performed on
      bone marrow aspirates was positive for E canis. This method was not applied for
      the detection of A phagocytophilum. Treatment with doxycycline and imidocarb
      dipropionate resulted in both clinical and parasitologic cure. This is the first
      reported case of a mixed infection with E canis, H canis, and presumptive A
      phagocytophilum. The findings emphasize the value of cytology in offering a quick
      and inexpensive diagnosis in mixed tick-borne infections of dogs.

PMID- 15570565
TI  - Firm rib mass aspirate from a dog.
AB  - A 9-year-old intact male Miniature Schnauzer presented laterally recumbent,
      cachexic, and dehydrated with multiple firm bone masses and a bilaterally
      enlarged prostate. Fine-needle aspiration of a rib mass revealed numerous
      basophilic polygonal to fusiform cells predominantly found in small to large
      clusters. The cells exhibited cytologic criteria of malignancy and infrequently
      displayed large cytoplasmic vacuoles containing finely- to coarsely-stippled
      azurophilic material. The cytologic diagnosis was metastatic adenocarcinoma and
      was suspected to be prostatic or transitional cell in origin because of the
      azurophilic vacuoles within malignant cells. Gross and histologic findings
      confirmed the clinical and cytologic diagnosis of prostatic adenocarcinoma with
      widespread metastasis. Cytochemical and immunohistochemical investigation
      confirmed glycogen was a component of the vacuolar material. The vacuoles
      observed in the tumor in this case are not a consistent finding in tumors of the
      prostate or urinary bladder; however, when associated with an epithelial tumor,
      they may aid in limiting the differentials of the primary tumor and in the
      selection of further diagnostics.

PMID- 15570567
TI  - Multimodality approaches for rectal cancer.

PMID- 15570568
TI  - The influence of nonspecific cleavage sites on identification of low molecular
      mass proteins by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry with seamless post-source decay fragment ion analysis.

PMID- 15570569
TI  - Assessing intra, inter and total agreement with replicated readings.
AB  - In clinical studies, assessing agreement of multiple readings on the same subject
      plays an important role in the evaluation of continuous measurement scale. The
      multiple readings within a subject may be replicated readings by using the same
      method or/and readings by using several methods (e.g. different technologies or
      several raters). The traditional agreement data for a given subject often consist
      of either replicated readings from only one method or multiple readings from
      several methods where only one reading is taken from each of these methods. In
      the first case, only intra-method agreement can be evaluated. In the second case,
      traditional agreement indices such as intra-class correlation (ICC) or
      concordance correlation coefficient (CCC) is often reported as inter-method
      agreement. We argue that these indices are in fact measures of total agreement
      that contains both inter and intra agreement. Only if there are replicated
      readings from several methods for a given subject, then one can assess intra,
      inter and total agreement simultaneously. In this paper, we present new inter
      method agreement index, inter-CCC, and total agreement index, total-CCC, for
      agreement data with replicated readings from several methods where the ICCs
      within methods are used to assess intra-method agreement for each of the several
      methods. The relationship of the total-CCC with the inter-CCC and the ICCs is
      investigated. We propose a generalized estimating equations approach for
      estimation and inference. Simulation studies are conducted to assess the
      performance of the proposed approach and data from a carotid stenosis screening
      study is used for illustration.

PMID- 15570570
TI  - Further studies on the fragmentation of protonated ions of peptides containing
      aspartic acid, glutamic acid, cysteine sulfinic acid, and cysteine sulfonic acid.
AB  - Here we examined the fragmentation, on a quadrupole ion-trap mass spectrometer,
      of the protonated ions of a group of peptides containing one arginine and two
      different acidic amino acids, one being aspartic acid (Asp) or glutamic acid
      (Glu) and the other being cysteine sulfinic acid [C(SO2H)] or cysteine sulfonic
      acid [C(SO3H)]. Our results showed that, upon collisional activation, the
      cleavage of the peptide bond C-terminal to C(SO2H) is much more facile than that
      of the peptide bond C-terminal to Asp, Glu, or C(SO3H). There is no significant
      difference, however, in susceptibility to cleavage of peptide bonds that are C
      terminal to Asp, Glu, and C(SO3H). To understand these experimental observations,
      we carried out B3LYP/6-31G* density functional theory calculations for a model
      cleavage reaction of GXG --> b2 + Gly, in which X is Asp, Glu, C(SO2H), or
      C(SO3H). Our calculation results showed that the cleavage reaction is
      thermodynamically more favorable when X = C(SO2H) than when X = Asp or C(SO3H).
      We attributed the less facile cleavage of the amide bond after Glu to that the
      formation of a six-membered ring b ion for Glu-bearing peptides is kinetically
      not as favorable as the formation of a five-membered ring b ion for peptides
      containing the other three acidic amino acids. The results from this study may
      provide useful tools for peptide sequencing.

PMID- 15570571
TI  - Atmospheric pressure chemical ionisation liquid chromatography/multistage mass
      spectrometry for assignment of sedimentary bacteriochlorophyll derivatives.
AB  - Atmospheric pressure chemical ionisation liquid chromatography/multistage mass
      spectrometry (APCI-LC/MSn) provides a rapid, on-line method for the assignment of
      individual bacteriophaeophorbide c and d methyl esters (BPMEs) in complex
      mixtures. The MS2 spectrum for each component is diagnostic of the type of BPME
      (c or d), and characteristic losses in MS5 and MS6 permit assignment of the alkyl
      substituents at positions C-8 and C-12 of the macrocycle. MS5 mass chromatograms
      permit the deconvolution of coeluting isobaric BPMEs, revealing the true profiles
      of the individual components. The distributions are different in lake sediments
      from la Salada de Chiprana (Spain) and Kirisjes Pond (Antarctica), and a novel
      BPME c with a neo-pentyl substituent has been observed in the Kirisjes Pond
      sediment.

PMID- 15570572
TI  - Automated immobilized metal affinity chromatography/nano-liquid
      chromatography/electrospray ionization mass spectrometry platform for profiling
      protein phosphorylation sites.
AB  - A versatile integrated system has been developed for the automated enrichment and
      analysis of phosphopeptides by immobilized metal affinity chromatography/nano
      liquid chromatography/electrospray ionization mass spectrometry (IMAC/nano-LC/ESI
      MS). This system utilizes two independently controlled high-performance liquid
      chromatography (HPLC) pumps, an autosampler and microvalves to prepare and elute
      samples into an ion trap mass spectrometer. The use of robust reversed-phase HPLC
      columns with integrated ESI emitter tips enables the reproducible detection and
      identification of low-femtomole quantities of phosphopeptides. The entire system
      is coordinated through a simple user interface by customized software. The
      ruggedness of the system is demonstrated by highly reproducible analyses of
      single and multi-protein digests, while its utility is demonstrated by the
      thorough evaluation of the relative immunoprecipitation efficiencies of several
      commercially available anti-phosphotyrosine antibodies.

PMID- 15570573
TI  - Validating regulatory-compliant wide dynamic range bioanalytical assays using
      chip-based nanoelectrospray tandem mass spectrometry.
AB  - Automated chip-based infusion nanoelectrospray ionization coupled to tandem mass
      spectrometry (nanoESI-MS/MS) was used to validate a bioanalytical assay
      conforming to United States Food and Drug Administration (FDA) regulatory
      guidelines and Good Laboratory Practices (GLP). Reboxetine was used as the
      analyte fortified in dog plasma along with an analog internal standard (IS). The
      best nanoESI response for reboxetine was observed with 90% acetonitrile
      (ACN)/water without any mobile phase modifiers. The analyte and IS were extracted
      from dog plasma samples by liquid-liquid extraction (LLE). The supernatant was
      concentrated to dryness and redissolved in 90% ACN/water for nanoESI. Selected
      reaction monitoring (SRM) data were collected for all samples to generate ion
      current profiles with a base width of approximately 20 s. Selectivity experiments
      showed no interferences in blank plasma samples. Interferences as a result of in
      source collision-induced dissociation of metabolites were not an issue due to the
      previously documented metabolism of reboxetine. Matrix suppression was evaluated
      across multiple lots of dog plasma as well as over different animal species
      (rabbit, rat, mouse) and different anticoagulants (heparin, EDTA). Matrix
      suppression ranged from approximately 30-60% across the different lots, species
      etc.; however, in all instances, the analyte and the IS were suppressed by
      similar amounts, suggesting the similarity in ionization properties between the
      two. A three-batch validation was performed (each batch consisting of four
      different concentrations, six replicates of each concentration) and demonstrated
      inter-assay accuracy (% relative error; RE) of less than +/-8% and an inter-assay
      precision (% relative standard deviation; RSD) of less than 7%, thus meeting
      regulatory guidelines. A comparison of analyses by nanoESI-MS/MS and liquid
      chromatography coupled to tandem mass spectrometry (LC/MS/MS) showed that nanoESI
      MS/MS had a greater slope for the calibration standard curve compared to
      LC/MS/MS, indicating greater sensitivity for the former technique. It is also
      noteworthy that the amount of sample infused during nanoESI-MS/MS was
      approximately 80-fold less compared to the amount of sample injected during
      LC/MS/MS. The absence of carryover (attributed to the lack of a common fluid
      path) in the nanoESI technique enabled the extension of the assay linear dynamic
      range to 500,000-fold, and the possibility of analyzing samples in a single batch
      without the need for re-analysis of samples with high concentrations. This
      technology offers the possibility for increased throughput for studies supporting
      drug development by providing fast data turnaround for assays conforming to
      regulatory guidelines and GLPs.

PMID- 15570574
TI  - Post-treatment emergent adverse events in depressed patients following treatment
      with milnacipran and paroxetine.

PMID- 15570575
TI  - Electrospray ionization tandem mass spectrometric study of three isomeric
      substituted aromatic sulfonic acids; differentiation via ortho effects.

PMID- 15570576
TI  - "Unblinding" in randomized controlled drug trials for urinary incontinence:
      Implications for assessing outcomes when adverse effects are evident.
AB  - AIMS: To determine whether women with urinary incontinence (UI) can identify
      their allocation in a randomized controlled trial (RCT) of tolterodine (TOL), and
      whether correct identification is associated with outcomes and adverse effects
      (AEs). METHODS: Exploratory analysis of a randomized, double-blind, placebo (PLC)
      controlled trial of TOL 4 mg daily for 8 weeks in 743 women with urge-predominant
      mixed UI. Patient perception of their randomization was assessed at trial end.
      Main outcome measures were 7-day bladder diaries, patient perception of
      improvement, and UI-specific quality of life (QoL). RESULTS: TOL produced a
      significant decrease in urge UI episodes compared to PLC (78% vs. 51%, P =
      0.0001). Fifty-one percent of women correctly identified their randomization (58%
      on TOL vs. 37% on PLC, P < 0.001). Women who assumed they took TOL had better
      bladder diary outcomes than those who assumed they took PLC. Within each
      assumption group, patient perception outcomes were similar, regardless of actual
      randomization. QoL improved in all domains except general health for women on
      TOL. In women who assumed they took TOL, significant drug benefit was evident in
      three domains. Moderate-severe dry mouth was higher in those who assumed they
      took TOL (7.3% vs. 0%, P < 0.0001). CONCLUSIONS: Greater than fifty percent of
      women in this RCT of antimuscarinic treatment were "unblinded" to their
      randomization. Patient assumption of randomization was associated with bladder
      diary and perception outcomes, specific QoL domains, and dry mouth. Efficacy of
      urge incontinence drugs should be considered in the context of patient
      assumptions, expectations, and "unblinding" by easily evident side effects.

PMID- 15570577
TI  - Oncolytic herpes simplex virus mutants are more efficacious than wild-type
      adenovirus Type 5 for the treatment of high-risk neuroblastomas in preclinical
      models.
AB  - BACKGROUND: High-risk neuroblastoma (Nb) is incurable using current treatment
      regimens in the majority of patients. Oncolytic virotherapy is a novel approach
      being tested for several types of adult cancers. OBJECTIVES: To compare the
      susceptibility of Nb tumor models to oncolytic adenovirus and HSV mutants and
      delineate the mechanisms of resistance or sensitivity. METHODS: Human Nb cell
      lines were used to determine susceptibility to adenovirus type 5 wild-type and
      HSV1 mutant (NV1066) infection, adenovirus receptor expression, support of NV1066
      replication, and induction of apoptosis. Human xenograft tumors in
      immunodeficient mice were evaluated for histological effects and tumor response
      to intratumoral injection of an oncolytic HSV mutant. RESULTS: All eight Nb cell
      lines tested in culture were relatively resistant to infection with wild type and
      attenuated adenoviruses. Cells expressed the cocksackie-adenovirus attachment
      receptor (CAR) but had low or absent expression of the internalization receptors
      (alphavbeta3, alphavbeta5 integrins). In contrast, all cells were uniformly
      sensitive to infection with the attenuated HSV mutant, NV1066. Productive virus
      replication and induction of apoptosis were observed in HSV-infected cells. CHLA
      20 and LAN-5 xenograft tumors injected with a single dose of NV1066 showed a
      significant antitumor response, and the animals had a prolonged survival post
      infection in comparison to the PBS-treated control group. HSV injected tumors
      showed extensive areas of necrosis and morphologic evidence of apoptosis.
      CONCLUSIONS: Nb tumor models are resistant to adenovirus mediated oncolysis but
      highly sensitive to HSV mediated oncolysis. Further studies of HSV virotherapy as
      a novel treatment for Nb are warranted.

PMID- 15570578
TI  - Intracellular Ca2+ regulation in a human prostate stromal cell culture.
AB  - AIMS: Prostate stromal cell cultures are used in vitro to study the cellular
      pathophysiology of benign prostatic hyperplasia (BPH), but their functional
      properties are poorly understood. This study characterized intracellular Ca2+
      ([Ca2+]i) regulation in a cultured cell line in comparison to freshly isolated
      cells, as a background to understanding contractile regulation and cellular
      proliferation in this tissue. METHODS: Prostate stromal cells were isolated from
      either PrS6 cell cultures, with an extended life span by transfection with the
      SV40 T-antigen, tsA58-U19, or freshly obtained transition zone prostate samples,
      primary cells. [Ca2+]i was measured in vitro with the indicator Fura-2 by
      epifluorescence microscopy. RESULTS: Phenylephrine, high-K+, and caffeine induced
      Ca2+-transients in primary cells (resting [Ca2+]i 94 +/- 8 nM, n = 29; peak 193
      +/- 26 nM, n = 19). In PrS6 cells resting [Ca2+]i was 96 +/- 8 nM (n = 78) and in
      34 of these 78 cells, 30 microM phenylephrine increased [Ca2+]i to 296 +/- 28 nM.
      5-methyl-urapidil (10-30 microM) inhibited this response in 10 of 16 cells.
      Spontaneous Ca2+-transients were also observed in 91% of phenylephrine-responsive
      cells, but in only 20% of non-responsive cells (P < 0.01). Ca2+-transients were
      also induced by high-K+ solution, and 20 mM caffeine. The latter abolished the
      response to subsequent phenylephrine application. Depletion of intracellular Ca2+
      stores by caffeine or restoration from a Ca2+-free superfusate caused a
      substantial rise of [Ca2+]i. CONCLUSIONS: PrS6 prostate stromal cells express
      functional alpha1-adrenoceptors associated with spontaneous intracellular Ca2+
      transients. They exhibit functional Ca2+ channels, intracellular Ca2+ stores, and
      Ca2+ entry induced by store depletion. Stromal cultures can therefore be used to
      characterize the cellular physiology of prostate stromal cell contraction and
      proliferation.

PMID- 15570579
TI  - Tension-free vaginal tape: do patients who fail to follow-up have the same
      results as those who do?
AB  - AIMS: To compare success and complication rates of the Tension-free vaginal tape
      (TVT) between patients with good versus poor follow-up. MATERIALS AND METHODS: A
      prospective cohort study of 108 women undergoing a TVT procedure was conducted.
      Patients were seen postoperatively at 6 weeks, 3, 6, 12 months, and yearly
      thereafter. Patients were categorized as poor follow-up if this schedule was not
      adhered to. Those who were lost to follow-up at or after their 6-week visit were
      considered as having failed the procedure. RESULTS: Seventy-nine (73%) patients
      had good follow-up. Of the remaining 29 patients with poor follow-up, 12 (11%)
      could not be reached and 17 (16%) were contacted by phone. Reasons given for poor
      follow-up were: busy or live far from hospital (11), health problems (4), and
      dissatisfied from surgery (2). Perioperative complication rates were similar
      between the two groups (P = 0.16). When patients with complete loss to follow-up
      were analyzed as failures, subjective and objective cure rates were significantly
      higher in patients with good as opposed to poor follow-up: 92 and 95% versus 72
      and 69%, respectively, (P = 0.006). CONCLUSIONS: Patients with poor follow-up
      probably have lower cure rates after TVT. It is important to follow postoperative
      patients closely. When reporting success rates, one has to account for all cases
      to produce realistic results.

PMID- 15570580
TI  - Net excitation of the motor unit pool varies with load type during fatiguing
      contractions.
AB  - To identify the underlying physiological mechanisms for the difference in the
      time to failure for two types of fatiguing contractions, 20 subjects performed
      force and position tasks with the elbow flexor muscles at a comparable net muscle
      torque for a similar duration. Prior to terminating each task, blood flow was
      occluded to estimate the relative amount of feedback transmitted by small
      diameter afferents to the spinal cord. Mean arterial pressure at the conclusion
      of the fatiguing contraction increased similarly for the two tasks (force: 119%
      +/- 14%; position: 114% +/- 15%). However, the final values for the
      electromyographic activity for the elbow flexor muscles (26% +/- 14% and 21% +/-
      11%, respectively; P < 0.05), and the increase in the fluctuations in
      acceleration and force (225% +/- 152% and 154% +/- 53%, respectively; P < 0.05)
      in the sagittal plane, were significantly greater during the position task
      compared with the force task. These results suggest a different balance in the
      excitatory and inhibitory inputs to the spinal motor neurons for the two tasks,
      which has implications for the design of work tasks and exercise prescription in
      rehabilitation.

PMID- 15570581
TI  - Reply by authors: "Technique of urethral retro-resistance pressure measurement".

PMID- 15570582
TI  - Evidence that rehydrated, lyophilized red blood cells are sufficiently deformable
      for normal microcirculation transit.
AB  - A method was developed for the preparation of rehydratable lyophilized red blood
      cells (RL RBCs) that hold promise as cell-based oxygen carriers for transfusion
      medicine. The maintenance of normal cellular deformability is essential for the
      successful development of cell-based oxygen delivery systems. Improper
      deformability of RBCs can lead to hemolysis if too fragile or microvascular
      occlusion if too rigid. We developed an aldehyde stabilization method that is
      based on the use of paraformaldehyde polymers that complement the function of
      spectrin as a structural unit with conformational flexibility. Three types of in
      vitro deformability studies (filter transit, pipette aspiration, and atomic force
      microscopy) and in vivo intravital microscopy were performed to characterize the
      deformability of RL RBCs. When considered with safety data from previously
      reported studies in dogs, the results of these studies indicate that
      paraformaldehyde-modified RL RBCs have visco-elastic deformability properties
      that are in the nonpathological range.

PMID- 15570583
TI  - Automatic segmentation of diatom images for classification.
AB  - A general framework for automatic segmentation of diatom images is presented.
      This segmentation is a critical first step in contour-based methods for automatic
      identification of diatoms by computerized image analysis. We review existing
      results, adapt popular segmentation methods to this difficult problem, and
      finally develop a method that substantially improves existing results. This
      method is based on the watershed segmentation from mathematical morphology, and
      belongs to the class of hybrid segmentation techniques. The novelty of the method
      is the use of connected operators for the computation and selection of markers, a
      critical ingredient in the watershed method to avoid over-segmentation. All
      methods considered were used to extract binary contours from a large database of
      diatom images, and the quality of the contours was evaluated both visually and
      based on identification performance.

PMID- 15570584
TI  - Current literature in diabetes.

PMID- 15570586
TI  - Complex wavelets for extended depth-of-field: a new method for the fusion of
      multichannel microscopy images.
AB  - Microscopy imaging often suffers from limited depth-of-field. However, the
      specimen can be "optically sectioned" by moving the object along the optical
      axis. Then different areas appear in focus in different images. Extended depth-of
      field is a fusion algorithm that combines those images into one single sharp
      composite. One promising method is based on the wavelet transform. Here, we show
      how the wavelet-based image fusion technique can be improved and easily extended
      to multichannel data. First, we propose the use of complex-valued wavelet bases,
      which seem to outperform traditional real-valued wavelet transforms. Second, we
      introduce a way to apply this technique for multichannel images that suppresses
      artifacts and does not introduce false colors, an important requirement for
      multichannel optical microscopy imaging. We evaluate our method on simulated
      image stacks and give results relevant to biological imaging.

PMID- 15570587
TI  - Coordinated expression of myosin heavy chains, metabolic enzymes, and
      morphological features of porcine skeletal muscle fiber types.
AB  - Combined methodologies of electrophoresis, immunoblots, immunohistochemistry,
      histochemistry, and photometric image analysis were applied to characterize
      porcine skeletal muscle fibers according to their myosin heavy chain (MyHC)
      composition, and to determine on a fiber-to-fiber basis the correlation between
      contractile [MyHC (s), myofibrillar ATPase (mATPase), and sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA) isoforms], metabolic [succinate dehydrogenase
      (SDH), and glycerol-3-phosphate dehydrogenase (GPDH) activities, glycogen, and
      phospholamban (PLB) contents], and morphological [cross-sectional area (CSA),
      capillary, and nuclear densities] features of individual myofibers. An accurate
      delineation of MyHC-based fiber types was obtained with the immunohistochemical
      method developed. This protocol showed a high sensitivity and objectivity to
      delineate hybrid fibers with overwhelming dominance of one MyHC isoform. The
      phenotypic differences in contractile, metabolic, and morphological properties
      seen between fiber types were related with MyHC content. Slow fibers had the
      lowest mATPase activity (related to shortening velocity), the highest SDH
      activity (oxidative capacity), the lowest GPDH activity (glycolytic metabolism),
      and glycogen content, the smallest CSA, the greatest capillary, and nuclear
      densities, and expressed slow SERCA isoform and PLB, but not the fast SERCA
      isoform. The reverse pattern was true for pure IIB fibers, whereas type IIA and
      IIX fibers had intermediate properties. Hybrid fibers had mean values
      intermediate in-between their respective pure phenotypes. Discrimination of
      myofibers according to their MyHC content was possible on the basis of their
      contractile and non-contractile profiles. These intrafiber interrelationships
      suggest that myofibers of control pigs exhibit a high degree of co-ordination in
      their physiological, biochemical, and anatomical features. This study may well be
      a useful baseline for future work on the pig meat industry and also offers new
      prospects for muscle fiber typing in porcine experimental studies.

PMID- 15570588
TI  - Terminal nerve and vision.
AB  - The vertebrate retina receives efferent input from different parts of the central
      nervous system. Efferent fibers are thought to influence retinal information
      processing but their functional role is not well understood. One of the best
      described retinopetal fiber systems in teleost retinae belongs to the terminal
      nerve complex. Gonadotropin-releasing hormone (GnRH) and molluscan
      cardioexcitatory tetrapeptide (FMRFamide)-containing fibers from the ganglion of
      the terminal nerve form a dense fiber plexus in the retina at the border of the
      inner nuclear and inner plexiform layer. Peptide-containing fibers surround and
      contact perikarya of dopaminergic interplexiform cells in teleost retina. In
      vitro experiments demonstrated that exogenously supplied GnRH mediates
      dopaminergic effects on the membrane potential and on the morphology of dendritic
      tips (spinules) of cone horizontal cells. These effects can be specifically
      blocked by GnRH-antagonists, indicating that the release of dopamine and dopamine
      dependent effects on light adaptation of retinal neurons are affected by the
      terminal nerve complex. Recent data have shown that olfactory information has an
      impact on retinal physiology, but its precise role is not clear. The efferent
      fiber of the terminal nerve complex is one of the first retinopetal fiber systems
      for which the sources of the fibers, their cellular targets, and several
      physiological, morphological, and behavioral effects are known. The terminal
      nerve complex is therefore a model system for the analysis of local information
      processing which is influenced by a distinct fiber projection.

PMID- 15570589
TI  - Development of the nervus terminalis: origin and migration.
AB  - The origin of the nervus terminalis is one of the least well understood
      developmental events involved in generating the cranial ganglia of the forebrain
      in vertebrate animals. This cranial nerve forms at the formidable interface of
      the anteriormost limits of migrating cranial neural crest cells, the terminal end
      of the neural tube and the differentiating olfactory and adenohypophyseal
      placodes. The complex cellular interactions that give rise to the various
      structures associated with the sensory placode (olfactory) and endocrine placode
      (adenohypophysis) surround and engulf this enigmatic cranial nerve. The tortured
      history of nervus terminalis development (see von Bartheld, this issue, pages 13
      24) reflects the lack of consensus on the origin (or origins), as well as the
      experimental difficulties in uncovering the origin, of the nervus terminalis.
      Recent technical advances have allowed us to make headway in understanding the
      origin(s) of this nerve. The emergence of the externally fertilized zebrafish
      embryo as a model system for developmental biology and genetics has shed new
      light on this century-old problem. Coupled with new developmental models are
      techniques that allow us to trace lineage, visualize gene expression, and
      genetically ablate cells, adding to our experimental tools with which to follow
      up on studies provided by our scientific predecessors. Through these techniques,
      a picture is emerging in which the origin of at least a subset of the nervus
      terminalis cells lies in the cranial neural crest. In this review, the data
      surrounding this finding will be discussed in light of recent findings on neural
      crest and placode origins.

PMID- 15570590
TI  - Ultrastructure of in situ perfusion-fixed avian liver, with special reference to
      structure of the sinusoids.
AB  - Broiler chicken and laying hen livers were fixed using a simple technique of in
      situ puncture perfusion of cacodylate-buffered fixative, which allowed
      characterisation of the fine structure of hepatic parenchyma, hepatocytes, bile
      ductules, and, in particular, the sinusoidal cells including endothelial,
      Kupffer, and Ito cells. Sinusoidal endothelial cells with their bulging
      perinuclear cytoplasm, evident in both transmission and scanning electron
      micrographs, were easily distinguishable from Kupffer cells, which possessed
      numerous pseudopodia. Bile ductular epithelium and hepatocytes of the laying hens
      contained large amounts of lipid. The ultrastructural characteristics of
      intercalated cells (putative extra-sinusoidal macrophages of chicken liver) are
      described and their possible role as precursors of Kupffer cells is discussed.

PMID- 15570591
TI  - Introduction to the anatomy and function of the nervus terminalis.

PMID- 15570592
TI  - The terminal nerve and its relation with extrabulbar "olfactory" projections:
      lessons from lampreys and lungfishes.
AB  - The definition of the terminal nerve has led to considerable confusion and
      controversy. This review analyzes the current state of knowledge as well as
      diverging opinions about the existence, components, and definition of terminal
      nerves or their components, with emphasis on lampreys and lungfishes. I will
      argue that the historical terminology regarding this cranial nerve embraces a
      definition of a terminal nerve that is compatible with its existence in all
      vertebrate species. This review further summarizes classical and more recent
      anatomical, developmental, neurochemical, and molecular evidence suggesting that
      a multitude of terminalis cell types, not only those expressing gonadotropin
      releasing hormone, migrate various distances into the forebrain. This results in
      numerous morphological and neurochemically distinct phenotypes of neurons, with a
      continuum spanning from olfactory receptor-like neurons in the olfactory
      epithelium to typical large ganglion cells that accompany the classical olfactory
      projections. These cell bodies may lose their peripheral connections with the
      olfactory epithelium, and their central projections or cell bodies may enter the
      forebrain at several locations. Since "olfactory" marker proteins can be
      expressed in bona fide nervus terminalis cells, so-called extrabulbar "olfactory"
      projections may be a collection of disguised nervus terminalis components. If we
      do not allow this pleiomorphic collection of nerves to be considered within a
      terminal nerve framework, then the only alternative is to invent a highly species
      and stage-specific, and, ultimately, thoroughly confusing nomenclature for
      neurons and nerve fibers that associate with the olfactory nerve and forebrain.

PMID- 15570593
TI  - Structural and antigenic preservation of plant samples by microwave-enhanced
      fixation, using dedicated hardware, minimizing heat-related effects.
AB  - We explored the use of microwave technology in fixation with the objective of
      achieving quicker fixation regimes, lower concentrations of toxic and volatile
      reagents, and enhanced antigen detection. We used a modified domestic microwave
      oven (900 W) and a low-power (5 W) microwave bench. The work was done on plant
      materials. The oven was supplemented with a cooling device, a stirring system,
      and a record of the sample temperature and the time of effective irradiation. The
      sample, immersed in a fixative solution of 1% paraformaldehyde (PFA) in PBS, was
      irradiated for only 10 minutes. The sample temperature did not exceed 37 degrees
      C. In these mild conditions, the quality of the (ultra)structural preservation of
      the samples, morphometrically assessed, was at the same level as obtained with
      the same fixative, using conventional methods. On the contrary, samples fixed in
      the same conditions without irradiation showed a poor structural preservation.
      The antigenic preservation of the irradiated samples was excellent, since the
      labeling levels of two nucleolar proteins, detected by immunogold, were three
      times higher than in conventionally fixed samples. In the so-called microwave
      bench, the pathway of microwaves is guided, so that low-power microwaves directly
      hit the sample and there is no dispersion of energy. Temperature of fixative did
      not increase after microwave irradiation. Fixation in the bench with either 4%
      PFA, or 1% PFA, for 20 minutes resulted in structural preservation of samples
      similar in quality as obtained with conventional fixation and in a similar or
      better level of antigen preservation. Therefore, controlling temperature and
      effective irradiation is crucial in order to obtain optimal structural and
      antigen preservation with microwave-enhanced fixation. The dramatic differences
      observed between microwave-irradiated samples and samples fixed in the same
      conditions without irradiation, strongly support the existence of specific
      effects of microwaves on fixation, independent from the mere heating of the
      samples.

PMID- 15570594
TI  - CLSM analysis of the phalloidin-stained muscle system in Nerilla antennata,
      Nerillidium sp. and Trochonerilla mobilis (Polychaeta; Nerillidae).
AB  - The entire muscle system of Nerilla antennata, Nerillidium sp. and Trochonerilla
      mobilis was three-dimensionally reconstructed from whole mounts. In juvenile and
      adult specimens the F-actin musculature subset was stained with FITC-conjugated
      phalloidin and visualized with a confocal laser scanning microscope (cLSM). The
      muscle system shows the following major organization: 1) circular muscles are
      totally absent in the body wall; 2) the longitudinal muscles are confined in two
      ventral and two dorsal thick bundles; 3) additional longitudinal muscles are
      located in the ventro- and dorsomedian axis; 4) three segmental pairs of ventral
      oblique muscles elongate into the periphery: the main dorsoventral muscles that
      run along the body side posterior and dorsally and the anterior and posterior
      oblique parapodial muscles, which contribute to the ventral chaetal sacs; 5) one
      segmental pair of dorsal oblique parapodial muscles, contributing to the dorsal
      chaetal sacs; 6) five to seven small dorsoventral muscles per segment; and 7)
      complex head and pharyngeal musculature. These results support the belief that
      absence of circular muscles in the polychaete body wall is much more widely
      distributed than is currently presumed.

PMID- 15570595
TI  - Spatial and functional modeling of carnivore and insectivore molariform teeth.
AB  - The interaction between the two main competing geometric determinants of teeth
      (the geometry of function and the geometry of occlusion) were investigated
      through the construction of three-dimensional spatial models of several mammalian
      tooth forms (carnassial, insectivore premolar, zalambdodont, dilambdodont, and
      tribosphenic). These models aim to emulate the shape and function of mammalian
      teeth. The geometric principles of occlusion relating to single- and double
      crested teeth are reviewed. Function was considered using engineering principles
      that relate tooth shape to function. Substantial similarity between the models
      and mammalian teeth were achieved. Differences between the two indicate the
      influence of tooth strength, geometric relations between upper and lower teeth
      (including the presence of the protocone), and wear on tooth morphology. The
      concept of "autocclusion" is expanded to include any morphological features that
      ensure proper alignment of cusps on the same tooth and other teeth in the tooth
      row. It is concluded that the tooth forms examined are auto-aligning, and do not
      require additional morphological guides for correct alignment. The model of
      therian molars constructed by Crompton and Sita-Lumsden ([1970] Nature 227:197
      199) is reconstructed in 3D space to show that their hypothesis of crest geometry
      is erroneous, and that their model is a special case of a more general class of
      models.

PMID- 15570596
TI  - Cell proliferation dynamics and morphological differentiation during regeneration
      in Dorvillea bermudensis (Polychaeta, Dorvilleidae).
AB  - Although some species of Annelida have an enormous capacity to regenerate, it is
      not yet known whether reestablishment of lost body parts is performed by stem
      cells, depends on preceding dedifferentiation of somatic cells, or is a
      combination of both. In order to clarify how, in the case of epimorphic
      regeneration, the blastemas are formed, we applied the thymidine analog 5'-bromo
      2'-deoxyuridine (BrdU) in the dorvilleid polychaete Dorvillea bermudensis to
      identify cells in the S-phase of the cell cycle. Regeneration pulse-chase
      experiments were carried out to determine onset and dynamics of the proliferation
      process, and BrdU pulse-chase experiments were undertaken to follow cell fate. We
      found irregularly distributed S-phase cells throughout the body of adult
      specimens. Subsequent to amputation, these cells do not migrate from the amputee
      towards the wound site, where proliferation activity was documented no earlier
      than 16 h after fragmentation. In the initial phase, the proliferation rate at
      the anterior end exceeds the rate at the posterior end. Observance of identity
      could be demonstrated for the ectoderm and can be assumed for the two other germ
      layers. The anterior blastema transforms into the head, while the posterior forms
      the pygidium and persists as a proliferation zone; four or numerous segments are
      formed by intercalation between the former anterior or posterior blastema and the
      amputee.

PMID- 15570597
TI  - Postcranial skeleton of Shinisaurus crocodilurus (Squamata: Anguimorpha).
AB  - The postcranial skeleton is poorly known for Shinisaurus crocodilurus, the
      Chinese crocodile lizard. Discrepancies exist between published accounts of
      Shinisaurus; moreover, comparisons with complete specimens show important
      differences from the published descriptions. Contrary to some publications, the
      axial skeleton variably consists of 26 or 27 presacral vertebrae, including eight
      cervical vertebrae. Humeral entepicondylar and ectepicondylar foramina are
      present, as are an epipubis and hypoischium, and the post-tubercular portion of
      the pubis is subequal in length to the proximal portion. Sesamoids are present in
      the knee, elbow, and between the penultimate phalanges and unguals. A
      cartilaginous strut joins the clavicles and interclavicle. Comparative
      investigation of extant anguimorphs add context to these observations and support
      the conclusion that Mosasauroidea possessed eight or more (rather than seven)
      cervical vertebrae. Overall, the postcranium of Shinisaurus is relatively
      unspecialized for Anguimorpha, although it may be diagnosed accurately by a
      combination of character states.

PMID- 15570598
TI  - Solubilization and preformulation studies on PG-300995 (an anti-HIV drug).
AB  - This study investigates the solubilization of a potential anti-human
      immunodeficiency virus agent [PG-300995 or 2-(2-thiophenyl)-4-azabenzoimidazole]
      for oral administration. The intrinsic solubility of PG-300995 is 51 microg/mL.
      Multiple approaches including combinations of pH control and cosolvency,
      micellization, or complexation were used to improve the solubility of PG-300995.
      The combined techniques increased the solubility of both the unionized and
      ionized species. The solubility of the drug increased from 20 to 200 times
      depending on the pH and concentration of solubilization agents. The following
      formulations which contain the desired doses of 5 and 10 mg/mL were developed for
      oral administration. Formulation A: 10 mg/mL PG-300995 in 20% sulfobutyl ether
      beta-cyclodextrin at pH 2; formulations B: 5 mg/mL PG-300995 in 10% sulfobutyl
      ether-beta-cyclodextrin at pH 2; formulation C: 5 mg/mL PG-300995 in 10% ethanol
      + 40% propylene glycol at pH 2. No precipitation was observed after series
      dilution of these three formulations with water or pH 2 buffers. These
      formulations are stable for at least 6 months after storing at room temperature
      and 37 degrees C.

PMID- 15570599
TI  - Kinetics and mechanism of the reaction of cysteine and hydrogen peroxide in
      aqueous solution.
AB  - The oxidation of thiol-containing small molecules, peptides, and proteins in the
      presence of peroxides is of increasing biological and pharmaceutical interest.
      Although such reactions have been widely studied there does not appear to be a
      consensus in the literature as to the reaction products formed under various
      conditions, the reaction stoichiometry, and the reaction mechanisms that may be
      involved. This study examines the reaction kinetics of cysteine (CSH) with
      hydrogen peroxide (H(2)O(2)) in aqueous buffers (in the absence of metal ions)
      over a wide range of pH (pH 4-13) and at varying ratios of initial reactant
      concentrations to explore the range of conditions in which a two-step
      nucleophilic model describes the kinetics. The disappearance of CSH and H(2)O(2)
      and appearance of cystine (CSSC) versus time were monitored by reverse-phase high
      performance liquid chromatography (HPLC). The effects of oxygen, metal ions
      (Cu(2+)), pH (4-13), ionic strength, buffer concentration, and temperature were
      evaluated. Data obtained at [H(2)O(2)](0)/[CSH](0) ratios from 0.01-2.3
      demonstrate that the reaction of CSH with H(2)O(2) in the absence of metal ions
      is quantitatively consistent with a two-step nucleophilic reaction mechanism
      involving rate-determining nucleophilic attack of thiolate anion on the unionized
      H(2)O(2) to generate cysteine sulfenic acid (CSOH) as an intermediate. Second
      order rate constants for both reaction steps were generated through model
      fitting. At [H(2)O(2)](0)/[CSH](0) > 10, the % CSSC formed as a product of the
      reaction declines due to the increased importance of alternative competing
      pathways for consumption of CSOH. A thorough understanding of the mechanism in
      aqueous solution will provide valuable background information for current studies
      aimed at elucidating the influence of such factors on thiol oxidation in solid
      state formulations.

PMID- 15570600
TI  - Heterogeneous nucleation-controlled particulate formation of recombinant human
      platelet-activating factor acetylhydrolase in pharmaceutical formulation.
AB  - Clinical lots of recombinant human platelet-activating factor acetylhydrolase
      (rhPAF-AH) were prepared in a lyophilized formulation. After reconstitution with
      sterile water for injection to form an aqueous solution (10 mM sodium citrate,
      7.5 w/v% sucrose, and 0.1 w/v% Pluronic-F68, pH 6.5), a few visible, slowly
      growing particles formed consistently within hours at room temperature. To
      investigate the mechanism of this phenomenon, immediately after reconstitution,
      all protein aggregates and exogenous particles were removed by filtration. During
      20 days incubation at room temperature, no visible aggregates formed in these
      filtered samples. In contrast, when nano-sized hydrophilic silica particles were
      added, they seeded rapid and extensive aggregation of rhPAF-AH. This effect was
      exacerbated in solutions containing a lower Pluronic-F68 concentration at 0.01%.
      Aggregation occurred even under conditions where rhPAF-AH adsorption was
      reversible, and induced no detectable changes to protein secondary and tertiary
      structures. Decreasing the extent (e.g., adding Pluronic-F68) or affinity (e.g.,
      increasing solution pH) of rhPAF-AH adsorption on nano-sized silica particles was
      found to be effective at reducing aggregation. Accelerated aggregation was not
      observed when rhPAF-AH formulation was seeded with aggregated rhPAF-AH. These
      results show that rhPAF-AH aggregation proceeds through a heterogeneous
      nucleation-controlled mechanism, where exogenous particles present in solution
      serve as seeds on which rhPAF-AH adsorb, nucleate, and grow into large
      aggregates.

PMID- 15570601
TI  - Glass transition-related changes in molecular mobility below glass transition
      temperature of freeze-dried formulations, as measured by dielectric spectroscopy
      and solid state nuclear magnetic resonance.
AB  - The purpose of this study was to explore why changes in the molecular mobility
      associated with glass transition, the timescale of which is on the order of 100
      s, can be detected by measuring the nuclear magnetic resonance relaxation times
      that reflect molecular motions on the order of 10 kHz and 1 MHz. The molecular
      motions in freeze-dried dextran 40k, dextran 1k, isomaltotriose (IMT), and alpha
      glucose comprising a common unit but with different glass transition
      temperatures, were investigated by dielectric spectroscopy (DES) in the frequency
      range of 0.01 Hz to 100 kHz and in the temperature range of -20 degrees to 200
      degrees C, in order to compare with the molecular motions reflected in nuclear
      magnetic resonance relaxation times. The alpha-relaxation process for freeze
      dried alpha-glucose was visualized by DES, whereas those for freeze-dried dextran
      40k, dextran 1k, and IMT were too slow to be visualized by DES. The latter freeze
      dried cakes exhibited quasi-dc polarization because of proton-hopping-like motion
      rather than alpha-relaxation process. The correlation time (tau(c)) for the
      backbone carbon of dextran 40k and IMT, calculated from the measured value of
      spin-lattice relaxation time in the rotating frame, was found to be close to the
      relaxation time of proton-hopping-like motion determined by DES (tau(DES)) at
      temperatures around glass transition temperature. The timescales of molecular
      motions reflected in the tau(c) and tau(DES) were significantly smaller than that
      of motions leading to molecular rearrangement (molecular rearrangement motions),
      which correspond to alpha-relaxation. However, the shapes of temperature
      dependence for the tau(c) and tau(DES) were similar to that of the
      calorimetrically determined relaxation time of molecular rearrangement motions.
      Results suggest that the molecular motions reflected in the tau(c) and tau(DES)
      are linked to molecular rearrangement motions, such that enhancement of molecular
      rearrangement motions enhances the molecular motions reflected in the tau(c) and
      tau(DES). Thus, the tau(DES) and tau(c) can reflect changes in molecular mobility
      leading to unwanted changes in amorphous formulations, and are thought to be a
      useful measure for evaluating the stability of formulations.

PMID- 15570602
TI  - Effect of the covalent modification with poly(ethylene glycol) on alpha
      chymotrypsin stability upon encapsulation in poly(lactic-co-glycolic)
      microspheres.
AB  - The effectiveness of the covalent modification of alpha-chymotrypsin with methoxy
      poly(ethylene glycol) (PEG) to afford its stabilization during encapsulation in
      poly(lactic-co-glycolic) acid (PLGA) microspheres by a solid-in-oil-in-water
      method was investigated. alpha-Chymotrypsin was chemically modified with PEG
      (M(w) = 5000) using molar ratios of PEG-to-chymotrypsin ranging from 0.4 to 96.
      Various conjugates were obtained and the amount of PEG modification was
      determined by capillary electrophoresis. In this investigation, only those
      conjugates with PEG/chymotrypsin molar ratios between approximately 1 and 8 were
      considered because higher levels of modification caused protein instability even
      before encapsulation. The stability and functionality of the chymotrypsin
      formulations were investigated before encapsulation by measuring enzyme kinetics,
      thermal stability, and tertiary structure intactness, and after the initial
      lyophilization process by determining the secondary structure content. These
      stability parameters were related to select ones after encapsulation in PLGA
      microspheres (specifically, the amount of insoluble aggregates, residual enzyme
      activity, and magnitude of protein structural perturbations). The results show
      that the more stable the protein conformation before encapsulation was, the
      higher was the retention of the specific activity after encapsulation. In
      contrast, no relationship was found between the protein stability before
      encapsulation and the magnitude of encapsulation-induced protein aggregation.
      Even the lowest level of modification (PEG-to-chymotrypsin molar ratio of 0.7)
      drastically reduced the amount of insoluble aggregates from 18% for the
      nonmodified protein to 4%. The results demonstrate that PEG modification was able
      to largely prevent chymotrypsin aggregation and activity loss upon solid-in-oil
      in-water encapsulation in PLGA microspheres. It is demonstrated that it is
      essential to optimize the degree of protein modification to ascertain protein
      stability upon encapsulation.

PMID- 15570603
TI  - Effect of fruit juices on the oral bioavailability of fexofenadine in rats.
AB  - Fexofenadine has been identified as a substrate for both the efflux transporter,
      P-glycoprotein (P-gp), as well as the influx transporter, organic anion
      transporting polypeptide (OATP). Clinical studies in humans showed that fruit
      juices reduced the oral bioavailability of fexofenadine by preferentially
      inhibiting OATP over P-gp. The objective of this study was to investigate the
      effects of fruit juices on the oral absorption of fexofenadine in rats to
      establish a preclinical fruit juice-drug interaction model. In rats, fexofenadine
      was excreted unchanged in the urine, bile, and gastrointestinal tract, indicating
      minimal metabolism, making it an ideal probe to study transport processes.
      Coadministration of fexofenadine with ketoconazole, a P-gp inhibitor, increased
      the oral exposure of fexofenadine by 187%. In contrast, coadministration of
      fexofenadine with orange juice or apple juice to rats decreased the oral exposure
      of fexofenadine by 31 and 22%, respectively. Increasing the quantity of orange or
      apple juice administered further decreased the oral exposure of fexofenadine, by
      40 and 28%, respectively. This reduction in fexofenadine bioavailability was
      moderate compared to that seen in humans. These findings suggest that in rats
      fruit juices may also preferentially inhibit OATP rather than P-gp-mediated
      transport in fexofenadine oral absorption, albeit to a lesser extent than
      observed in humans. This fruit juice--drug interaction rat model may be useful in
      prediction of potential food--drug interactions in humans for drug candidates.

PMID- 15570604
TI  - Evaluation of dodecylmaltoside as a permeability enhancer for insulin using human
      carcinoma cells.
AB  - Dodecylmaltoside (DDM), an alkylglycoside showing tissue-permeability-enhancing
      properties, has been successful in improving nasal and ocular transport of poorly
      absorbed drugs. It was hypothesized that optimization of DDM concentration would
      improve the transport of insulin across epithelial monolayers without causing
      cell damage. Samples of markers and insulin were collected over a 6-h period and
      transepithelial electrical resistance was measured at concurrent time points to
      ascertain the effect of DDM on tight junctions. Samples were analyzed for lucifer
      yellow and insulin using reversed-phase high-performance liquid chromatography
      and for (3)[H]-mannitol by scintillation counting. A significant increase in the
      transport of markers and insulin was recorded in DDM-treated cells compared with
      controls. DDM enhanced the transport of markers and insulin in a concentration
      dependent manner. Decreased transepithelial electrical resistance values
      confirmed that enhanced transport is caused by loosening of tight junctions. Cell
      recovery was >95% in 8 h indicating the potential of DDM as a penetration
      enhancer for clinical administration of insulin and other poorly absorbed drugs
      without causing cell damage.

PMID- 15570605
TI  - Rheology and NMR self-diffusion experiments as well as skin permeation of
      diclofenac-sodium and cyproterone acetate of new gel preparations.
AB  - The viscoelastic properties of two transparent semisolid preparations, one
      consisting of surfactant, paraffin oil, and water (BAS), and the other consisting
      of surfactant, cetylstearyl-2-ethylhexanoate, and water (CUBO), were
      characterized by oscillatory measurements. In (1)H-NMR diffusion experiments it
      was confirmed that the formulations are O/W systems, and the three-dimensional
      packing of the closed globular aggregates form a cubic structure. Moreover,
      standard diffusion experiments with porcine skin using Franz cells were performed
      with incorporated diclofenac-sodium and cyproterone acetate, respectively. The
      cumulative amount released after 48 h of diclofenac-sodium were excellent with
      665.28 microg/cm(2) and with 36.7 microg/cm(2) for cyproterone acetate. The new
      drug-containing formulations were also prepared as transdermal patches by using
      carrageenan as a matrix. In diffusion studies zero-order kinetics was found for
      both drugs, but with a higher lag time for cyproterone acetate. The total work of
      adhesion was analyzed by tensile studies on porcine skin and found to be very
      good. The presented cubic gels as well as mixtures with carrageenan are promising
      alternative drug carrier systems for topical pharmaceutical as well as cosmetics.

PMID- 15570606
TI  - Tea tree oil concentration in follicular casts after topical delivery:
      determination by high-performance thin layer chromatography using a perfused
      bovine udder model.
AB  - Tea tree oil, a popular antimicrobial agent is recommended for the treatment of
      acne vulgaris, a disease of the pilosebaceous unit. Tea tree oil formulations
      (colloidal bed, microemulsion, multiple emulsion, and liposomal dispersion
      containing 5% w/w tea tree oil) were applied to bovine udder skin. The follicular
      uptake of tea tree oil upon application was determined by a cyanoacrylate method.
      Tea tree oil was determined by quantifying terpinen-4-ol content using high
      performance thin layer chromatography. The accumulation of tea tree oil in the
      follicular casts was 0.43 +/- 0.01, 0.41 +/- 0.009, 0.21 +/- 0.006, and 0.16 +/-
      0.005 percentage by weight (milligram oil/gram of sebum plug) for microemulsion,
      liposomal dispersion, multiple emulsion, and colloidal bed, respectively. This is
      the first study of its kind to quantify tea tree oil concentration in the
      follicles.

PMID- 15570607
TI  - Mechanism of the stationary canalicular excretion of tributylmethyl ammonium in
      rats with a CCl4-induced acute hepatic injury.
AB  - The in vivo canalicular excretion clearance of tributylmethyl ammonium (TBuMA), a
      P-glycoprotein (P-gp) substrate, was previously reported to be unaffected by the
      induction of an experimental hepatic injury (EHI) by CCl(4) despite the increased
      expression of P-gp in the EHI liver. The objective of this study, therefore, was
      to elucidate the mechanism for the unchanged canalicular excretion clearance of
      TBuMA in EHI rats. TBuMA uptake was increased in cLPM vesicles from EHI rats
      compared with that from control rats. The total bile salt concentration in EHI
      liver was significantly reduced compared with that in a control liver. Because,
      in our previous studies, the uptake of TBuMA by cLPM vesicles was found to be
      significantly enhanced in the presence of bile salts, the reduction in bile salt
      levels in the EHI liver may be related to the unaltered TBuMA clearance. Despite
      the fact that the uptake of TBuMA by cLPM vesicles was increased by the addition
      of an EHI liver extract, the extent of the increase was comparatively less
      compared to the addition of a control liver extract. The in vivo excretion
      clearance of TBuMA was increased in a taurodeoxycholate dose-dependent manner in
      EHI rats. These observations suggest, therefore, that despite the induction of P
      gp expression by the EHI, the in vivo canalicular excretion clearance of TBuMA
      remains unaltered as the result of an offset by reduced levels of bile salt(s).

PMID- 15570608
TI  - Ultrastructural observations of spermatozoa of several tetragnathid spiders with
      phylogenetic implications (Araneae, Tetragnathidae).
AB  - The present study reports on the ultrastructure of spermatozoa and
      spermatogenesis of 12 tetragnathid spiders (10 Tetragnatha species [T. boydi, T.
      dearmata, T. extensa, T. montana, T. nigrita, T. obtusa, T. pinicola, T.
      reimoseri, T. shoshone, T. striata]; Pachygnatha listeri and Metellina
      segmentata). All species develop typical cleistospermia with a coiled nucleus in
      the center and a coiled axoneme in the periphery of the cell. Remarkable
      differences in the sperm ultrastructure of the investigated species comprise the
      shape of the main sperm cell components (nucleus, acrosomal complex, implantation
      fossa, and centriolar complex). Within the observed Tetragnatha species, three
      types of sperms were characterized: T. montana-type, T. boydi-type, and T.
      striata-type. The highly derivative T. montana-type is characterized by the
      following remarkable features: an extremely elongated nucleus, shaped like a
      corkscrew and twisted around the axoneme (before coiling); a deep implantation
      fossa; a corkscrew-shaped acrosomal vacuole; after the coiling process, the
      nucleus is coiled five to six times in the center of the spermatozoon and the
      axoneme is coiled five to six times peripheral to the nucleus. The T. boydi-type
      hardly differs from the T. montana-type, but is remarkable due to the triangular
      shaped nucleus (in cross section). The T. striata-type differs especially by a
      peculiar acrosomal vacuole with a long, slightly curved process and a short
      appendix, as well as a nucleus that describes only three loose coils around the
      axoneme (before coiling). The spermatozoa of Pachygnatha listeri and especially
      Metellina segmentata differ strikingly from the described Tetragnatha-types and
      are similar to more primitive araneomorph spermatozoa, such as Hypochilus
      pococki. The described Tetragnatha-types completely correspond with Okuma's
      (1988a,b, J Fac Agr Kyushu U 32:165-181, 32:183-213) classification of
      Tetragnatha species. Furthermore, our results suggest an early derivative
      systematic position of Pachygnatha within Tetragnathinae and the position of
      Metellina within the Tetragnathidae.

PMID- 15570609
TI  - Descriptive epidemiology of lipomyelomeningocele, Hawaii, 1986-2001.
AB  - BACKGROUND: The epidemiology of neural tube defects (NTDs) may depend on the type
      of the defect and its location. There is little epidemiologic information on
      lipomyelomeningocele, a type of NTD. The objective of this investigation was to
      describe the epidemiology of lipomyelomeningocele. METHODS: Cases were obtained
      from a Hawaii birth defect registry and consisted of all infants delivered during
      1986-2001 with lipomyelomeningocele. Lipomyelomeningocele rates per 10,000 births
      were calculated for various factors. RESULTS: A total of 17 cases of
      lipomyelomeningocele were identified, for a total rate of 0.57. When the
      lipomyelomeningocele rate was examined with respect to the time period of folic
      acid fortification of cereal grains in the United States, the rate was 0.57
      during 1986-1996 (prefortification), 0.57 during 1997-1998 (voluntary
      fortification), and 0.58 during 1999-2001 (mandatory fortification). A total of
      11 (64.7%) of the cases were female. Lipomyelomeningocele rates were higher among
      infants born to mothers in younger and older age groups. The rate was highest
      among Pacific Islanders, followed by Filipinos and Far East Asians, and lowest
      among whites. Rates were greater with lower birth weight and gestational age and
      among multiple births. CONCLUSIONS: Lipomyelomeningocele rates were not found to
      be affected by folic acid fortification. The majority of cases were female. Other
      demographic and clinical factors appear to be associated with
      lipomyelomeningocele risk. None of the differences in rates between the various
      subgroups were statistically significant, and due to the small number of cases,
      the 95% confidence interval (CI) ranges were wide. However, the findings suggest
      possible patterns of occurrence. Additional studies involving larger numbers of
      cases are recommended.

PMID- 15570610
TI  - Postmarketing surveillance for drug safety in pregnancy: the Organization of
      Teratology Information Services project.
AB  - BACKGROUND: Although medications are frequently used during pregnancy,
      premarketing studies exclude pregnant women, with the result that maternal and
      fetal risks of medications are largely unknown prior to marketing. METHODS: To
      demonstrate the feasibility of using Teratology Information Services (TISs) to
      identify potential subjects who may participate in postmarketing surveillance
      studies regarding medications taken during pregnancy, maternal characteristics
      and pregnancy exposure data routinely collected from callers to member agencies
      of the Organization of Teratology Information Services (OTIS) were pooled for two
      one-month periods. RESULTS: A total of 3536 calls inquiring about 7746 different
      agents were received from pregnant women. Of the 40 medications about which
      pregnant women most frequently asked, the top two were nonprescription
      acetaminophen and pseudoephedrine, three were prescription drugs with a U.S. Food
      and Drug Administration pregnancy label category D designation, and five were
      prescription antidepressants. CONCLUSIONS: TISs are well positioned to
      prospectively ascertain medication exposures in large numbers of pregnant women
      and may be an exceptional resource for conducting postmarketing surveillance for
      the safety of medications taken during pregnancy.

PMID- 15570611
TI  - Identification of bovine and novel interferon-tau alleles in the American plains
      bison (Bison bison) by analysis of hybrid cattle x bison blastocysts.
AB  - The objective of this study was to generate bison x cattle hybrid embryos by in
      vitro fertilization, to assess their developmental potential, to determine the
      pattern of secretion of the embryonic signaling molecule interferon-tau (IFN
      tau), and to identify novel IFN-tau mRNA polymorphism in the American plains
      bison. A total of 600 bovine oocytes were inseminated with frozen-thawed bison
      semen. Of these, 40.7% cleaved and 14.8% proceeded to the blastocyst stage.
      Individual blastocysts were cultured on a basement membrane (Matrigel) and their
      ability to attach and form outgrowths was monitored. A total of 36 blastocysts
      were cultured of which 22 formed outgrowths. During individual culture, medium
      samples were collected and their IFN-tau concentration was measured. On day 6
      after onset of individual culture, attached outgrowths produced significantly
      more IFN-tau than unattached viable or degenerate blastocysts. At this time,
      female conceptuses also produced significantly more IFN-tau than their male
      cohorts. However, by day 12 this difference had disappeared. Total mRNA was
      extracted from three individual outgrowths and analyzed by RT-PCR. Subsequent
      sequencing of 28 clones showed several known bovine IFN-tau sequences as well as
      two novel sequences termed bisIFN-tau1 and 2. To determine the origin of these,
      DNA was extracted from bison semen and analyzed by PCR. One bovine IFN-tau
      sequence (bovIFN-tau1d) as well as bisIFN-tau2 and a third novel sequence bisIFN
      tau3 were detected. This study demonstrates the feasibility of using hybrid
      embryos for the analysis of developmentally regulated gene expression in species
      where embryos may not be available.

PMID- 15570612
TI  - MEK inhibitors block AICAR-induced maturation in mouse oocytes by a MAPK
      independent mechanism.
AB  - The present study was carried out to assess the possible role of mitogen
      activated protein kinase (MAPK) in the meiosis-inducing action of the AMP
      activated protein kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide 1-beta
      ribofuranoside (AICAR). Cumulus cell-enclosed oocytes (CEO) or denuded oocytes
      (DO) from immature, eCG-primed mice were cultured 4 hr in Eagle's minimum
      essential medium containing dbcAMP plus increasing concentrations of AICAR or
      okadaic acid (OA). OA is a phosphatase inhibitor known to stimulate both meiotic
      maturation and MAPK activation and served as a positive control. Both OA and
      AICAR were potent inducers of meiotic resumption in mouse oocytes and brought
      about the phosphorylation (and thus, activation) of MAPK, but by different
      kinetics: MAPK phosphorylation preceded GVB in OA-treated oocytes, while that
      resulting from AICAR treatment appeared only after GVB. The MEK inhibitors,
      PD98059 and U0126, blocked the meiotic resumption induced by AICAR but not that
      induced by OA. Although the MEK inhibitors suppressed MAPK phosphorylation in
      both OA- and AICAR-treated oocytes, meiotic resumption was not causally linked to
      MAPK phosphorylation in either group. Furthermore, AICAR-induced meiotic
      resumption in Mos-null oocytes (which are unable to stimulate MAPK) was also
      abrogated by PD98059 treatment. A non-specific effect of the MEK inhibitors on
      AICAR accessibility to the oocyte was discounted by showing that they failed to
      suppress either nucleoside uptake or AICAR-stimulated phosphorylation of acetyl
      CoA carboxylase (ACC), a substrate of AMPK. The suppression of AICAR-induced
      maturation by MEK inhibitors must, therefore, be occurring by actions unrelated
      to MEK stimulation of MAPK; consequently, it would be prudent to consider this
      possible non-specific action of the inhibitors when they are used to block MAPK
      activation in mouse oocytes.

PMID- 15570613
TI  - Androstenedione increases cytochrome P450 aromatase messenger ribonucleic acid
      transcripts in nonluteinizing bovine granulosa cells.
AB  - The objective of this study was to determine if androgens regulate granulosa cell
      steroidogenesis at physiological doses found in small bovine follicles. Bovine
      granulosa cells were cultured under serum-free conditions that permit the
      induction and maintenance of FSH-dependent estradiol secretion. Increasing
      androstenedione concentrations from 0.1 to 1 or 10 microM significantly increased
      estradiol accumulation and cytochrome P450 aromatase (P450arom) mRNA abundance.
      No increase in progesterone accumulation or abundance of mRNA for P450 side-chain
      cleavage or 3beta-hydroxysteroid dehydrogenase enzymes was observed. The addition
      of 0.1, 1, or 10 microM progestins or estrogens had no stimulatory effect on
      P450arom mRNA levels. An analysis of the 5'-untranslated region of P450arom mRNA
      transcripts indicated that the majority was derived from Cyp19 ovary-specific
      promoter 2, with some contribution from promoters 1.1 and 1.5. Transcripts from
      these three promoters were all significantly increased by androstenedione.
      Testosterone increased promoter 1.1 and 1.5-derived transcripts, but only
      promoter 2-derived transcripts at the highest dose tested (100 microM).
      Dihydrotestosterone (DHT) did not affect Cyp19 expression. Collectively, these
      data show that androgens may exert specific stimulatory effects on P450arom mRNA
      concentrations in granulosa cells. Interestingly, different androgens had
      different effects on Cyp19 promoter usage, suggesting differential regulation of
      aromatase gene expression in the developing follicle.

PMID- 15570614
TI  - Actin polymerization in the equatorial and postacrosomal regions of guinea pig
      spermatozoa during the acrosome reaction is regulated by G proteins.
AB  - The acrosome reaction (AR) is an exocytotic process of spermatozoa, and an
      absolute requirement for fertilization. During AR, actin polymerization is
      necessary in the equatorial and postacrosomal regions of guinea pig sperm for
      spermatozoa incorporation deep into the egg cytoplasm, but not for plasma
      membrane (PM) fusion nor the early steps of egg activation. To identify the
      mechanisms involved in this sperm actin polymerization, we searched for the
      protein members, known to be involved in a highly conserved model, that may apply
      to any cellular process in which de novo actin polymerization occurs from G
      protein activation. WASP, Arp 2/3, profilins I and II, and Cdc42, RhoA and RhoB
      GTPases were localized by indirect immunofluorescence (IIF) in guinea pig
      spermatozoa and their presence corroborated by Western blotting. WASP and
      profilin II were translocated to the postacrosomal region (Arp2/3 already were
      there) in long-term capacitated and acrosome-reacted spermatozoa, at the same
      time as actin polymerization occurred. These events were inhibited by GDP-beta-S
      and promoted by lysophosphatidic acid (LPA) and GTP-gamma-S, a small GTPase
      inhibitor and two activators, respectively. By immunoprecipitation, Cdc42-WASp
      association was identified in capacitated but not in noncapacitated gametes.
      Polymerized actin in the postacrosomal region is apparently anchored both to the
      postacrosomal perinuclear theca region and the overlying PM. Results suggest that
      GTPases are involved in sperm actin polymerization, in the postacrosomal region
      and the mechanism for polymerization might fit a previously proposed model
      (Mullins, 2000: Curr Opin Cell Biol 12:91-96).

PMID- 15570615
TI  - Matrix metalloproteinase-2 (MMP-2) expression and regulation by tumor necrosis
      factor alpha (TNFalpha) in the bovine corpus luteum.
AB  - Angiogenesis and tissue remodeling events in the corpus luteum (CL) are mediated
      by matrix metalloproteinases (MMPs). We have recently reported the cloning of
      bovine membrane-type 1 metalloproteinase (MT1-MMP) and have shown that active MT1
      MMP is correlated to MMP-2 activity in the CL during the estrous cycle. Given the
      important role that MMP-2 plays in neovascularization, we became interested in
      understanding the role of this enzyme in the CL, a system in which angiogenesis
      is exquisitely regulated in the course of its lifespan. The aims of the present
      study were to clone bovine MMP-2 cDNA, to investigate its temporal and spatial
      expression in three stages of CL during the estrous cycle and to study its
      regulation by TNFalpha, a key cytokine regulator of CL physiology. Bovine MMP-2
      cDNA was isolated from a UNI-ZAP II bovine capillary endothelial cell cDNA
      library and sequenced. This gene encoded a protein of 662 amino acids. Luteal
      tissues were collected from non-lactating dairy cows on days 4, 10, and 16 of the
      estrous cycle. Northern and Western blotting revealed that the levels of MMP-2
      mRNA (3.1 kb) and immunoreactive pro-MMP-2 protein (68 kDa) did not differ (P >
      0.05) in any age of CL examined. In addition to large luteal cells, MMP2 was
      localized to endothelial cells in all ages of CL by immunohistochemistry. Studies
      using in vitro luteal cell cultures showed that MMP-2 mRNA, protein expression
      and activity was upregulated by TNFalpha in a dose- and time-dependent manner.
      The present study suggests that MMP-2 is predominantly produced by large luteal
      cells and endothelial cells, and that it plays an essential role in luteal
      remodeling and angiogenesis. These data also suggest that cytokines such as
      TNFalpha may modulate these processes by regulating MMP-2 expression.

PMID- 15570616
TI  - Ultrastructure and cell death of in vivo derived and vitrified porcine
      blastocysts.
AB  - Morphological and molecular signs of injury and cell death and subsequent
      regeneration following vitrification of porcine blastocysts were evaluated by
      light (LM) and transmission electron microscopy (TEM) as well as TUNEL/propidium
      iodide (PI) nuclear staining followed by confocal microscopy (CSM). In vivo
      derived blastocysts were assigned to one of the following four groups: Controls
      (1) fixed immediately after collection (C0h) and (2) after 24 hr culture in vitro
      (C24h) and vitrified embryos-(3) fixed immediately after vitrification and
      warming (V0h), and (4) after 24 hr of culture upon warming after vitrification
      (V24h). Observation by LM and TEM showed that the V0h embryos displayed collapse
      of the blastocoele cavity (BC) and cell swelling, a general distension or
      shrinkage of mitochondria and massive increase in the amount of vesicles,
      vacuoles, and secondary lysosomes (SLs). Approximately 2/3 of the V24h embryos
      had recovered, whereas the remaining 1/3 were degenerated. Recovered embryos
      displayed almost normal blastocyst morphology, except for a widening of the
      perivitelline space, accumulation of debris and partial distension of
      mitochondria, whereas degenerated embryos were disintegrated into a poorly
      defined mass of cells and debris including cells with abundant degeneration of
      mitochondria and other organelles. Both recovered and degenerated embryos
      displayed a persistent abundance of presence of small membrane bounded vesicles,
      vacuoles, and SLs. Evaluation of TUNEL/PI stained embryos showed only occasional
      appearance of TUNEL positive nuclei with typical apoptotic morphology in controls
      (C0h 0.67%, C24h 1.22%) and in the V0h embryos (0.93%). The percentage of
      apoptotic nuclei in embryos at V24h was significantly higher than in all other
      groups (2.64%). Vitrified embryos showed significantly increased appearance of
      DNA fragmented nuclei without typical morphological features of apoptosis (V0h
      1.43%, V24h 4.30%) compared with controls (C0h 0.26%, C24h 0.45%). The observed
      morphological changes and increased DNA fragmentation observed immediately after
      vitrification and warming probably reflects a direct damaging effect of
      vitrification. During 24 hr of culture a portion of the embryos was able to
      regenerate and along with the regenerative process, apoptosis--a possible pathway
      for elimination of damaged cells--became evident.

PMID- 15570617
TI  - Basic nuclear protein pattern and chromatin condensation in the male germ cells
      of a tropical abalone, Haliotis asinina.
AB  - The basic nuclear proteins (BNPs) in spermatozoa of a tropical abalone, Haliotis
      asinina, were composed of a majority of protamine-like (PL) protein and a small
      amount of histones H1 and H4. Abalone H1 and PL proteins exhibited strong
      immunological cross reactivities among themselves as well as with chick H5 and
      calf thymus H1. Thus, all these proteins may belong to the same family.
      Immunolocalization by indirect immunofluorescence and immunoelectron microscopy
      indicated that H1 and H4 were present in all steps of the male germ cells,
      however, with decreasing amount in late stage cells, particularly spermatids and
      spermatozoa. On the other hand, PL was present in middle step cells (secondary
      spermatocytes) with increasing amount in spermatids and spermatozoa when the
      chromatin became tightly packed. Thus, PL may be involved in the condensation of
      chromatin in the spermatozoa of this species.

PMID- 15570618
TI  - Participation of the nonreducing terminal beta-galactosyl residues of the neutral
      N-linked carbohydrate chains of porcine zona pellucida glycoproteins in sperm-egg
      binding.
AB  - The zona pellucida (ZP) surrounding the mammalian oocyte is composed of three
      glycoprotein components (ZPA, ZPB, and ZPC). Mammalian sperm bind to carbohydrate
      chains of a ZP glycoprotein in the initial phase of fertilization. Sperm-ligand
      carbohydrate chains have been characterized in mouse, cow, and pig. In pigs,
      triantennary/tetraantennary neutral complex-type chains from ZPB/ZPC mixture
      possess stronger sperm-binding activity than those of biantennary chains (Kudo et
      al., 1998: Eur J Biochem 252:492-499). Most of these oligosaccharides have beta
      galactosyl residues at the nonreducing ends. This study used two in vitro
      competition assays to investigate the participation of the nonreducing terminal
      beta-galactosyl residues of the ligand active chains in porcine sperm binding.
      The removal of the nonreducing terminal beta-galactosyl residues from either the
      ligand active carbohydrate chains or endo-beta-galactosidase-digested
      glycoproteins significantly reduced their inhibition of sperm-egg binding,
      indicating that the beta-galactosyl residues at the nonreducing ends are involved
      in porcine sperm-egg binding. A correlation between the sperm-binding activity
      and in vitro fertilization rate is also presented.

PMID- 15570619
TI  - Transcriptional activation of the membrane-bound progesterone receptor (mPR) by
      dioxin, in endocrine-responsive tissues.
AB  - We originally identified the membrane-bound progesterone receptor (mPR) using a
      screening for genes differentially expressed in liver of rats exposed to dioxin.
      Recent findings have suggested a role for the mPR in sperm cells, ovary, and
      brain; however, its mechanisms of action are largely unknown. In this study, we
      examined the expression pattern of the mPR in liver of rats exposed to dioxin and
      identified possible mechanisms of its regulation. We observed that mPR expression
      was induced by dioxin, but was also dependent on the hormonal responsiveness of
      the tissue. In particular, in male, but not female liver, dioxin induced the
      expression of the mPR. However, in control, untreated female liver the level of
      mPR transcript was higher than in control males. Moreover, in breast cancer cells
      MCF-7 dioxin induced mPR expression. Promoter studies using the luciferase assay
      indicated that a fragment of approximately 350 bp of the mPR promoter was able to
      induce luciferase activity in the presence of dioxin, suggesting that the
      presumptive XREs sites contained in this mPR promoter region are responsive to
      dioxin. Analysis of mPR protein level confirmed the results observed at the RNA
      level, both in rat liver and MCF-7 cells. Taken together, these observations
      suggest the existence of a novel cross-talk between steroid and aromatic
      hydrocarbon receptors (AhR), and underline the importance of the mPR as a
      mediator of physiologic effects of the sex hormones.

PMID- 15570620
TI  - Chromatin organization and basic nuclear proteins in the male germ cells of Rana
      tigerina.
AB  - The process of chromatin condensation during spermiogenesis in Rana tigerina is
      similar to the heterochromatization in somatic cells, where 30 nm fibers are
      coalesced together into a dense mass in spermatozoa without changing their
      initial size and nucleosomal organization. This conclusion was supported by the
      finding that the full set of core histones (H2A, H2B, H3, H4) are still present
      in sperm chromatin, but histone H1 is replaced by its variant, H1V. Rabbit anti
      sera were raised against histone H3, H1, H1V, and H5 (H1 variant in chick
      erythrocyte). Anti-histone H1 antiserum cross-reacted with histone H1V, which
      implied the presence of a common epitope. Anti-histone H1V and H5 also showed
      cross-reaction with each other but not with histone H1, which implied the
      presence of a common epitope not shared by histone H1. Immunocytochemical
      studies, using the above antibodies as probes, showed that histones H3 is present
      in all steps of spermatogenic and spermiogenic cells, and somatic cells including
      red blood cells, Sertoli cells, and Leydig cells, while histone H1 is present in
      all of the cells mentioned except in spermatozoa where it is replaced by histone
      H1V. Histone H1V appears in the early spermatids starting from spermatid 1 (St1),
      and it persists throughout the course of spermatid differentiation into
      spermatozoa. Histone H1V is also found in chromosomes of metaphase spermatocyte
      and red blood cells. Thus histone H1V may cause the final and complete
      condensation of chromatin in Rana spermatozoa, a process which is similar to the
      heterochromatization occurring in somatic cells such as metaphase chromosome and
      chick erythrocyte nucleus.

PMID- 15570621
TI  - Isolation and mapping the chicken zona pellucida genes: an insight into the
      evolution of orthologous genes in different species.
AB  - The avian oocyte is surrounded by a specialized extracellular glycoproteinaceous
      matrix, the perivitelline membrane, which is equivalent to the zona pellucida
      (ZP) in mammals and the chorion in teleosts. A number of related ZP genes encode
      the proteins that make up this matrix. These proteins play an important role in
      the sperm/egg interaction and may be involved in speciation. The human genome is
      known to contain ZP1, ZP2, ZP3, and ZPB genes, while a ZPAX gene has also been
      identified in Xenopus. The rapid evolution of these genes has confused the
      nomenclature and thus orthologous relationships across species. In order to
      clarify these homologies, we have identified ZP1, ZP2, ZPC, ZPB, and ZPAX genes
      in the chicken and mapped them to chromosomes 5, 14, 10, 6, and 3, respectively,
      establishing conserved synteny with human and mouse. The amino acid sequences of
      these genes were compared to the orthologous genes in human, mouse, and Xenopus,
      and have given us an insight into the evolution of these genes in a variety of
      different species. The presence of the ZPAX gene in the chicken has highlighted a
      pattern of probable gene loss by deletion in mouse and gene inactivation by
      deletion, and base substitution in human.

PMID- 15570622
TI  - Cloned pre-implantation mouse embryos show correct timing but altered levels of
      gene expression.
AB  - Mammalian embryos obtained by somatic nuclear transfer (NT) struggle to survive
      throughout development, encountering a number of hurdles leading to wrong
      functional reprogramming of the donor genome. However, despite these obstacles,
      some of these embryos continue their development, as if the required
      transcriptional functions are somehow satisfied. The amount of information
      gathered on the kinetics and quantitative profile of gene expression in NT pre
      implantation embryos is still scarce and limited to a handful of genes described
      in two species, bovine and mouse. Using a single-cell sensitive semi-quantitative
      RT-PCR, we have compared the onset and profile of abundance of Hprt, Tsx, Bex1,
      Bax, Cpt2, and Oct4 genes, in in vitro fertilised and NT-derived mouse 1-cell, 2
      cell, 4-cell embryos, morulae, and blastocysts. The genes analysed were activated
      in NT embryos at approximately the correct time compared to control embryos,
      indicating that the reprogramming phenomenon is developmentally regulated and
      that the somatic genome is quickly rearranged towards an embryonic-type of
      expression during the early stages of segmentation. Despite the right timing of
      genes onset, the high degree of variability in the number of transcripts found in
      NT embryos at the latest stages of pre-implantation development, suggests that
      genome reprogramming is incomplete and inaccurate.

PMID- 15570623
TI  - Adjusting for partially missing baseline measurements in randomized trials.
AB  - Adjustment for baseline variables in a randomized trial can increase power to
      detect a treatment effect. However, when baseline data are partly missing,
      analysis of complete cases is inefficient. We consider various possible
      improvements in the case of normally distributed baseline and outcome variables.
      Joint modelling of baseline and outcome is the most efficient method. Mean
      imputation is an excellent alternative, subject to three conditions. Firstly, if
      baseline and outcome are correlated more than about 0.6 then weighting should be
      used to allow for the greater information from complete cases. Secondly,
      imputation should be carried out in a deterministic way, using other baseline
      variables if possible, but not using randomized arm or outcome. Thirdly, if
      baselines are not missing completely at random, then a dummy variable for
      missingness should be included as a covariate (the missing indicator method). The
      methods are illustrated in a randomized trial in community psychiatry.

PMID- 15570624
TI  - RNA interference as a tool to study gene function in bovine oocytes.
AB  - RNA interference (RNAi) has become a well-established technique to study gene
      function in several species. Our objective was to develop a RNAi approach to
      study gene function in bovine oocytes. In the first experiment, three different
      treatments including a 20 min exposure to cytochalasin B, a 6 hr maturation in
      cycloheximide, and a combination of these two treatments were tested to improve
      oocyte survival following microinjection. The cycloheximide/cytochalasin B
      treatment greatly increased (P<0.02) the survival rate of the microinjected
      oocytes. In the second experiment, we assessed the effect of both cyclin B1 and
      GFP dsRNA on cyclin B1 mRNA and protein expression. The injection of cyclin B1
      dsRNA resulted in a decrease in cyclin B1 mRNA and protein, while the cyclin B2
      mRNA remained unaffected. Furthermore, the injection of GFP dsRNA did not
      interfere with cyclin B1 mRNA or protein nor with the ability of the oocyte to
      mature properly. In addition, the lack of cyclin B1 in the oocyte led to
      activation in 10% of the oocytes as evidenced by the presence of a pronucleus.
      However, the use of an additional 10 hr of maturation in the presence of 6
      dimethylaminopurine (6-DMAP) prevented germinal vesicle breakdown and allowed a
      longer exposure to dsRNA. This procedure increased the percentage of activated
      oocytes to 33% and is likely to result from an increased length of time for dsRNA
      processing and for degradation of the cyclin B1 mRNA to occur. In conclusion,
      RNAi represents a useful technique to study gene function in the bovine oocyte.

PMID- 15570625
TI  - The use of bootstrap methods for estimating sample size and analysing health
      related quality of life outcomes.
AB  - Health-related quality of life (HRQoL) measures are increasingly used in trials
      as primary outcome measures. Investigators are now asking statisticians for
      advice on how to plan and analyse studies using such outcomes. HRQoL outcomes,
      like the SF-36, are usual measured on an ordinal scale, although most
      investigators assume that there exists an underlying continuous latent variable
      and that the actual measured outcomes (the ordered categories) reflect contiguous
      intervals along this continuum. The ordinal scaling of HRQoL measures means they
      tend to generate data that have discrete, bounded and skewed distributions. Thus,
      standard methods of analysis that assume Normality and constant variance may not
      be appropriate. For this reason, conventional statistical advice would suggest
      non-parametric methods be used to analyse HRQoL data. The bootstrap is one such
      computer intensive non-parametric method for estimating sample sizes and
      analysing data. We describe three methods of estimating sample sizes for two
      group cross-sectional comparisons of HRQoL outcomes. We then compared the power
      of the three methods for a two-group cross-sectional study design using bootstrap
      simulation. The results showed that under the location shift alternative
      hypothesis, conventional methods of sample size estimation performed well,
      particularly Whitehead's method. Whitehead's method is recommended if the HRQoL
      outcome has a limited number of discrete values (<7) and/or the expected
      proportion of cases at either of the bounds is high. If a pilot data set is
      readily available then bootstrap simulation will provide a more accurate and
      reliable estimate, than conventional methods.Finally, we used the bootstrap for
      hypothesis testing and the estimation of standard errors and confidence intervals
      for parameters, in an example data set. We then compared and contrasted the
      bootstrap with standard methods of analysing HRQoL outcomes. In the data set
      studied, with the SF-36 outcome, the use of the bootstrap for estimating sample
      sizes and analysing HRQoL data produces results similar to conventional
      statistical methods. These results suggest that bootstrap methods are not more
      appropriate for analysing HRQoL outcome data than standard methods.

PMID- 15570626
TI  - Measuring the efficacy and effectiveness of rheumatoid arthritis therapy: time to
      change our thinking and adopt a new model.

PMID- 15570627
TI  - COPCORD--an unrecognized fountainhead of community rheumatology in developing
      countries.

PMID- 15570628
TI  - Chronic back pain: searching for causes and cures.

PMID- 15570629
TI  - Matrix catabolism in arthritis: priming the guns with oncostatin M.

PMID- 15570630
TI  - Classification criteria for antiphospholipid syndrome: the case for cardiac
      valvular disease.

PMID- 15570631
TI  - High dose immunotherapy with stem cell rescue in severe systemic sclerosis: an
      idea that is moving forward.

PMID- 15570632
TI  - A distinct multicytokine profile is associated with anti-cyclical citrullinated
      peptide antibodies in patients with early untreated inflammatory arthritis.
AB  - OBJECTIVE: Early inflammatory arthritis is clinically heterogenous and
      biologically-based indicators are needed to distinguish severe from self-limited
      disease. Anti-cyclical citrullinated peptides (CCP) have been identified as
      potential prognostic markers in early arthritis cohorts. Since cytokine networks
      are known to play a critical role in the pathogenesis of rheumatoid arthritis
      (RA) and other forms of inflammatory arthritis, a panel of pro- and
      antiinflammatory cytokines was measured to identify biologically-based subsets of
      early arthritis, relating cytokine profiles to clinical measures and to the
      presence of RA-associated autoantibodies. METHODS: Plasma concentrations of
      cytokines [interleukin 1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL
      8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF),
      granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-g (IFN-g),
      CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1beta), and tumor
      necrosis factor-a (TNF-a)] were measured in patients with early, untreated
      inflammatory arthritis [symptom duration < or = 12 months; > or = 1 swollen
      joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression
      patterns were determined using cluster analysis. RESULTS: Both pro- and
      antiinflammatory cytokines were elevated in patients over controls (n = 21). RA
      clustered into subgroups based solely on cytokine profiles. The "mild" RA
      subgroup (n = 23) had higher CCL4 (MIP-1beta), CXCL8 (IL-8), IL-2, IL-12, IL-17,
      IL-5, and IL-10 levels, lower IL-6, IFN-g, GM-CSF, and IL-4 levels, less CCP
      positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p <
      0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint
      counts compared to the "severe" RA groups. CCL4 (MIP-1beta), IL-13, IL-12, TNF-a,
      and IL-4 best distinguished the groups. Combining UA with RA samples preserved
      cytokine subgroups and strengthened the autoantibody associations. Fewer UA
      patients in the "mild" cluster (n = 16) were RF-positive (24% vs 100%; p < 0.002)
      or CCP-positive (24% vs 66%; p < 0.08) compared to the "severe" group.
      CONCLUSION: Early untreated inflammatory arthritis can be categorized into
      distinct subgroups based on cytokine profiles. These subgroups are associated
      with CCP and RF autoantibodies. Integration of cytokine profiles with
      autoantibody status may assist prognostication and treatment decisions in these
      patients.

PMID- 15570633
TI  - Enhanced Fcgamma receptor I, alphaMbeta2 integrin receptor expression by
      monocytes and neutrophils in rheumatoid arthritis: interaction with platelets.
AB  - OBJECTIVE: To investigate platelet and leukocyte activation and interaction in
      patients with rheumatoid arthritis (RA) and the effect of methotrexate (MTX) or
      anti-tumor necrosis factor-a (TNF-a) treatment on these variables. METHODS: Four
      color flow cytometry analysis was performed for quantitative measurement of
      platelet (P-selectin, PAC-1) and leukocyte (CD11b, CD64) activation markers and
      estimation of percentage of leukocyte-platelet complexes in whole blood in 20
      patients with RA before and after 6 weeks of therapy and in 20 controls. In
      addition, measures of soluble P-selectin (sP-selectin), beta-thromboglobulin,
      fibrinogen, prothrombin fragment 1+2, D-dimer, C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), and TNF-a and tender
      and swollen joint counts were carried out. RESULTS: Before therapy, PAC-1
      binding, expression of CD11b and CD64 on monocytes and neutrophils, circulating
      levels of monocyte (CD11b+ or CD64+)-platelet complexes, monocyte-PAC-1+ platelet
      complexes, CRP, ESR, IL-6, TNF-a, fibrinogen, D-dimer and sP-selectin were
      significantly higher in RA patients compared to controls. The anti-TNF-a therapy
      significantly reduced levels of monocyte-PAC-1+ platelet complexes, sP-selectin,
      CRP, ESR, IL-6, TNF-a, fibrinogen, and D-dimer and tender and swollen joint
      counts. CD64 expression on monocytes was significantly decreased by MTX therapy.
      PAC-1 binding was not inhibited by MTX or anti-TNF-a. CONCLUSION: Increased
      platelet and leukocyte activation and increased formation of leukocyte-platelet
      complexes in patients with RA suggest a status of simultaneous activation of the
      immune and hemostatic systems.

PMID- 15570634
TI  - Clinical outcomes of patients with rheumatoid arthritis after switching from
      infliximab to etanercept.
AB  - OBJECTIVE: To assess the efficacy and monitor serious adverse events in patients
      with rheumatoid arthritis (RA) switching treatment from infliximab to etanercept.
      METHODS: Adult patients with active RA who were discontinuing treatment with
      infliximab were eligible to enroll in this prospective, 12-week, open label,
      single-arm, observational study. Four to 10 weeks after their last infusion of
      infliximab, patients began treatment with etanercept (twice weekly subcutaneous
      injections of 25 mg). Clinical assessments using the American College of
      Rheumatology (ACR) criteria for improvement were performed at baseline and at
      Weeks 6 and 12, and serious adverse events were monitored throughout the study.
      RESULTS: Twenty-five patients were enrolled, 18 of whom had discontinued
      infliximab because of lack of efficacy, and 22 completed 12 weeks of etanercept
      treatment. After 12 weeks, 14 of 22 patients (64%) achieved at least a 20%
      improvement in ACR criteria (ACR20), 13 (59%) experienced improvements in
      physical function that were considered clinically important (> or = 0.22 point
      decrease in overall Health Assessment Questionnaire score), and mean values of
      all individual components of the ACR criteria had improved. No serious adverse
      events were reported during the study and no patient discontinued because of lack
      of efficacy. CONCLUSION: Etanercept, a soluble tumor necrosis factor (TNF)
      receptor, provided a well tolerated and effective treatment option for some
      patients even when infliximab, a monoclonal antibody to TNF, had been
      ineffective.

PMID- 15570635
TI  - Low dose methotrexate in the first trimester of pregnancy: results of a French
      collaborative study.
AB  - OBJECTIVE: To assess the risk of major malformations in pregnant women with
      chronic inflammatory disorders treated with low dose methotrexate (MTX) during
      the first trimester of pregnancy. Secondary outcomes included the rate of
      miscarriage, birth weight, and gestational age at delivery. METHODS: Data from
      the French network of 31 pharmacovigilance centers and 2 teratology information
      services were analyzed. The outcome of pregnancy was prospectively assessed in
      women exposed during the first trimester of pregnancy. Data on maternal history
      and drug exposure were collected at the initial inquiry, and on the outcome of
      pregnancy at followup. RESULTS: Twenty-eight cases were available for analysis.
      MTX exposure ended before 8 weeks of gestation in 26 patients. Miscarriages
      occurred in 4 patients and 5 had elective termination of pregnancy. There were 19
      live births, among whom 3 were premature. Birth weights in full-term children
      were within the expected range. One child exposed until 8.5 weeks of gestation
      had only minor anomalies (metatarsus varus and eyelid angioma). CONCLUSION:
      Although no definitive conclusion can be drawn, our results and the analysis of
      the literature support the conclusion that no strong teratogenic risk is
      associated with low dose MTX provided that the drug is discontinued as early as
      possible in pregnant women.

PMID- 15570636
TI  - Therapeutic strategies in rheumatoid arthritis over a 40-year period.
AB  - OBJECTIVE: To examine trends in therapeutic strategies and to identify the
      determinants of starting disease modifying antirheumatic drug (DMARD) therapy
      over a 40-year period in a population based inception cohort of patients with
      rheumatoid arthritis (RA). METHODS: A population based inception cohort was
      assembled from among all Rochester, Minnesota, residents aged > or = 18 years who
      were first diagnosed with RA (1987 American College of Rheumatology criteria)
      between January 1, 1955, and January 1, 1995. All subjects were followed
      longitudinally through their complete medical records until death, migration from
      Olmsted County, or date of abstraction (January 1, 2001, to January 1, 2003).
      Drug exposure data were collected on all DMARD and corticosteroid regimens. Time
      to DMARD initiation was examined using the Kaplan-Meier method. The influence of
      calendar time and disease characteristics on time from incidence to first DMARD
      therapy and the number of DMARD regimens were analyzed using Cox regression and
      proportional odds models, respectively. RESULTS: The study population comprised
      603 patients (73% female) with a mean age of 58 years and a mean followup of 15
      years. At 2 years after RA onset, 26% of patients in the 1955-74 cohort, 40% in
      the 1975-84 cohort, and 70% in the 1985-94 cohort had received a DMARD (log-rank
      p < 0.001). Age, rheumatoid factor (RF) positivity, erythrocyte sedimentation
      rate, large joint swelling, rheumatoid nodules, and destructive changes on
      radiographs were significantly associated with time to first DMARD regimen after
      adjustment for calendar time and sex. Patients who were older and RF positive and
      who did not receive CS were more likely to have received more DMARD regimens.
      CONCLUSION: Time to initiation of DMARD therapy has shortened markedly over the
      past 3-4 decades. These changes in management of early RA provide evidence for
      the translation of scientific evidence into clinical practice in rheumatology.
      Age and various disease characteristics are significantly associated with
      initiation and the number of DMARD regimens used. These should be considered as
      confounders when examining the effect of early DMARD treatment on disease
      progression and mortality.

PMID- 15570637
TI  - Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis
      treated with methotrexate, and the effect of low dose folic acid supplement.
AB  - OBJECTIVE: To investigate the effect of methotrexate (MTX) treatment of
      rheumatoid arthritis (RA) on folate metabolism, and to determine the effect of
      low dose folic acid on toxicity, efficacy, and folate status. METHODS: A 52-week
      prospective study of 81 patients with RA treated with MTX and self-administered
      low dose folic acid; 38 patients were included prior to MTX therapy, 33 patients
      continued established MTX therapy, and 10 patients were excluded. Drug efficacy
      and side effects were monitored with biochemical and clinical indicators.
      RESULTS: MTX treatment resulted in decreased concentrations of red blood cell
      (RBC) folate and a rise in plasma homocysteine. Intracellular concentrations of
      MTX were inversely correlated to RBC folate levels after treatment for a longer
      period (mean 41 months). Supplement with low dose folic acid prevented or
      diminished the influence of MTX on folate status and had a protective effect on
      MTX induced liver toxicity without changing the efficacy of MTX. CONCLUSION: MTX
      interferes with folate and homocysteine metabolism, and the intracellular
      concentration of MTX may play a role. Our results indicate low dose folic acid
      supplementation has a beneficial effect on MTX toxicity.

PMID- 15570638
TI  - Autoantibodies that stabilize U1snRNP are a significant component of human
      autoantibodies to snRNP and delay proteolysis of sm antigens in vitro.
AB  - OBJECTIVE: Autoantibodies to U1-C have been considered a minor component of anti
      snRNP (nRNP, Sm) response based on Western blotting. However, we have previously
      shown that virtually all human anti-nRNP sera contain antibodies to native U1-C,
      as well as novel autoantibodies that stabilize the molecular interaction of the
      U1-C-Sm core particle. The biological significance of stabilizing antibodies was
      investigated by titering anti-U1-C/U1-A compared to stabilizing antibodies, and
      by examining the effects of stabilizing antibodies on antigen processing.
      METHODS: Autoantibodies to individual native components of U1snRNP
      (immunoprecipitation of RNase-treated cell extract) and stabilizing antibodies
      (dissociation of snRNP on anti-Sm monoclonal antibodies by 1 M MgCl2) in human
      autoimmune sera were titered. Effects of stabilizing antibodies on proteolysis
      were assessed by incubating UsnRNP with anti-snRNP/Sm autoimmune sera prior to
      protease digestion. RESULTS: Autoantibodies to native U1-C and U1-C-Sm core
      particle stabilizing antibodies were universally present in human anti-nRNP or
      anti-nRNP + anti-Sm sera, but not in anti-Sm sera. Antibodies to U1-A were less
      common. The titers of stabilizing antibodies were higher than those of antibodies
      to U1-C (p < 0.01), indicating that the stabilizing antibodies were a significant
      component of the anti-snRNP response. The stabilizing anti-nRNP, but not anti-Sm
      antibodies, protects the Sm core particle from dissociation and proteolysis.
      CONCLUSION: Autoantibodies stabilizing the U1-C-Sm core particle were universally
      present in anti-nRNP sera and delay proteolysis of the Sm core particle. They may
      suppress spreading of the autoimmune response to Sm by delaying or altering
      processing of the Sm core proteins by antigen-presenting cells.

PMID- 15570639
TI  - Defining response in systemic lupus erythematosus: a study by the Systemic Lupus
      International Collaborating Clinics group.
AB  - OBJECTIVE: In a preliminary attempt to develop a drug responder index for
      patients with systemic lupus erythematosus (SLE), 2 validated disease activity
      instruments were studied for their responsiveness and compared to a physician
      visual analog scale (VAS) assessment of disease activity. We attempted to
      determine whether these validated instruments were useful components in
      characterizing response in the setting of a clinical trial. METHODS: Eighty paper
      patients were assessed using the British Isles Lupus Assessment Group (BILAG) and
      Systemic Lupus Disease Activity Index (SLEDAI) and by physician's assessment of
      global activity. The cases were arranged in random order and divided into groups
      of 20 patients and each group was assessed by 20 lupus experts; change in disease
      activity was recorded at 3 and 6 months compared to baseline using a physician
      VAS. RESULTS: Four different lupus experts assessed disease activity in all 80
      patients at baseline and 3 and 6 months after initiation of therapy using the
      BILAG and SLEDAI instruments. BILAG and SLEDAI scores correlated well over time;
      however, in a regression analysis where average physician VAS were chosen as the
      outcome variable, a significant amount of variation in the average physician VAS
      not related to the SLEDAI and BILAG scores was noted. CONCLUSION: The physician
      VAS may be too blunt to assess response in SLE, because even among experienced
      lupus assessors, there were considerable differences in what influenced scoring
      decisions.

PMID- 15570640
TI  - Systemic sclerosis and occupational risk factors: role of solvents and cleaning
      products.
AB  - OBJECTIVE: To analyze occupational and non-occupational exposure factors
      suspected of being associated with scleroderma (SSc), with a view to inculpating
      or excluding certain potentially toxic substances (e.g., solvents), thereby
      contributing to the recognition of such toxins in the field of occupational
      health. METHODS: The study comprised 10 men and 83 women diagnosed with SSc
      between 1995 and 1999 (American College of Rheumatology criteria) and early SSc,
      and 206 age and sex matched controls. The SSc registry is all-inclusive in the
      French administrative departments of Isere and Savoie so controls were randomly
      selected from the general population (using telephone directories) in these
      departments to ensure full representation. Exposure factors were analyzed for
      each subject by a personal questionnaire, and an individual evaluation was
      carried out by an industrial expert. Data were analyzed by conditional logistical
      regression adjusting for educational level. RESULTS: Construction workers were at
      significantly higher risk of contracting SSc; odds ratio (OR) = 4.01 (95%
      confidence interval 1.14-14.09). Analysis by industrial experts identified
      exposure to certain toxic substances regularly used by these same workers as risk
      factors for SSc: cleaning products: OR = 1.66 (0.90-3.08) (both sexes) and OR =
      1.71 (0.92-3.20) (women only); solvents: OR = 3.23 (1.58-6.63) (both sexes) and
      OR = 2.80 (1.28-6.11) (women only); synthetic adhesives: OR 25.36 (1.36-472.28)
      (on 3 exposed cases). CONCLUSION: Exposure to either cleaning products or
      solvents emerged as a risk factor for SSc. Exposure factors should be
      characterized and results of all studies compared to implement appropriate
      preventive measures in relevant workplaces.

PMID- 15570641
TI  - Primary antiphospholipid syndrome: a 5-year transesophageal echocardiographic
      followup study.
AB  - OBJECTIVE: To study valvular abnormalities in patients with primary
      antiphospholipid syndrome (APS) assessed by transesophageal echocardiography
      (TEE). METHODS: This was a 5-year followup study. Between 1995 and 1997, 29
      consecutive patients with primary APS were studied by TEE. Twenty-four patients
      were evaluated in our institution and 5 were referred from elsewhere. Four
      patients had died, 12 patients had the 5-year followup TEE, and 8 failed to
      report for the study. RESULTS: In the first TEE, valve lesions were found in 17
      patients (70.8%), myocardial infarction in 5 cases (29.4%), pulmonary
      hypertension in 4 (23.5%), and a calcified thrombus in the right atrium in one
      patient. Five-year followup TEE was performed in 12 patients. Valve lesions were
      unchanged in 3 cases, and in one of them a new apical akinesis of the left
      ventricle appeared. New valve lesions were detected in 3 patients. In 6 patients,
      the valve lesions had progressed and in 2, abnormalities of ventricular wall
      motion had appeared. CONCLUSION: In this highly selected population of patients
      with primary APS, the predominant cardiac lesion was a noninfective valve lesion.
      Oral anticoagulant treatment and aspirin proved ineffective in terms of valvular
      lesion regression. Altogether, myocardial infarction occurred in 9 (37.5%)
      patients. All had coronary angiography and coronary arteries were normal in 6.

PMID- 15570642
TI  - Low level laser therapy in primary Raynaud's phenomenon--results of a placebo
      controlled, double blind intervention study.
AB  - OBJECTIVE: To assess the efficacy of low level laser therapy in patients with
      primary Raynaud's phenomenon and predict the success of laser therapy by clinical
      characteristics. METHODS: Forty-eight patients were included in a randomized
      placebo controlled, double blind crossover study. Laser and sham therapy each
      were applied 5 days a week for 3 weeks. Clinical symptoms, exposure to triggers,
      and frequency and intensity of attacks were recorded in diaries. Results of
      infrared thermography before onset and at the end of both irradiation sequences
      were evaluated. Primary endpoint was the average intensity of attacks; secondary
      endpoints were average number of attacks and thermography results. Age, sex,
      duration of symptoms, age at onset of symptoms, evoking conditions other than
      cold, maximum temperature drop after cold provocation, and rewarming time after
      cold provocation were tested as potential predictors. RESULTS: Number of attacks
      and their intensity were significantly reduced during laser therapy compared to
      sham treatment. Thermographic parameters did not reach statistical significance.
      In a stepwise multiple regression analysis, evoking conditions other than cold
      (stress, wetness as additional triggers), rewarming time, and temperature
      decrease after cold provocation were significant predictors of therapeutic
      efficacy. CONCLUSION: Low level laser therapy reduces frequency and severity of
      Raynaud attacks. The effect is most pronounced in patients with signs of
      decreased threshold for vasospasm and less effective in patients with delayed
      hyperemia.

PMID- 15570643
TI  - Epistatic interactions between HLA-DRB1 and interleukin 4, but not interferon
      gamma, increase susceptibility to giant cell arteritis.
AB  - OBJECTIVE: To assess the roles of the interleukin 4 (IL-4) and interferon-g (IFN
      g) gene polymorphisms in a series of patients with biopsy-proven giant cell
      arteritis (GCA). METHODS: Eighty-two patients with biopsy-proven GCA and 102
      ethnically matched controls from the Lugo region (Northwest Spain) were studied.
      The following single nucleotide polymorphisms (SNP) were assessed: IL-4 (SNP1:
      rs2070874, SNP2: rs2227284, SNP3: rs2227282, SNP4: rs2243266, and SNP5:
      rs2243267) and IFN-g (SNP1: rs1861494, SNP2: rs1861493, and SNP3: rs2069718).
      RESULTS: Significant differences in allele and genotype frequencies were observed
      for the IL-4 SNP between HLA-DRB1*04 negative patients and controls. Epistatic
      interaction between SNP2 (rs2227284) with HLA-DRB1 showed a significant
      interaction (p = 0.001) and carriage of the SNP2*T allele in the absence of HLA
      DRB1*04 resulted in a 4-fold risk of developing GCA (OR 4.2, 95% CI 1.1-15.6).
      Also, a significant increase in the frequency of the T-T-C-A-C IL-4 haplotype was
      observed in HLA-DRB1*04 negative GCA patients compared to the controls (p = 0.02;
      OR 2.0, 95% CI 1.0-3.9). Similar distributions of allele and genotype frequencies
      were observed for the IFN-g polymorphisms in both GCA patients and controls.
      CONCLUSION: Our results suggest an association with IL-4 gene polymorphism that
      is dependent on HLA-DRB1 genotype in GCA susceptible individuals. These data
      indicate an interaction between HLA-DRB1 and IL-4 that contributes to pronounced
      disease susceptibility.

PMID- 15570644
TI  - Prolactin and growth hormone responses to hypoglycemia in patients with
      rheumatoid arthritis and ankylosing spondylitis.
AB  - OBJECTIVE: Prolactin (PRL) and growth hormone (GH) are pituitary hormones with
      immunomodulating properties. Their upregulated secretion may play a role in the
      pathogenesis of chronic inflammatory diseases. We evaluated PRL and GH responses
      to secretion stimulus in patients with rheumatoid arthritis (RA) and ankylosing
      spondylitis (AS). METHODS: Insulin hypoglycemia (0.1 IU/kg) was induced in 15
      women with RA, 18 men with AS, and healthy controls matched for age, sex and body
      mass index. Plasma concentrations of glucose, PRL, GH, interleukin 6 (IL-6), and
      tumor necrosis factor alpha (TNF-a) were analyzed. RESULTS: RA patients had
      significantly lower area under the curve (AUC) of PRL (p = 0.049) compared to RA
      controls. During hypoglycemia double or higher increase of plasma PRL occurred in
      5 RA (33%) patients and in 8 RA controls (57%). Using the General Linear Model
      procedure, no significant differences in PRL or GH responses were observed in
      patients with RA and AS. TNF-a was higher in patients with RA compared to RA
      controls (p < 0.05). There was no significant difference in TNF-a concentrations
      between AS patients and AS controls. IL-6 was higher in RA patients compared to
      controls (p < 0.05) and in AS patients compared to controls (p < 0.01).
      Significant positive correlation was found between TNF-a levels and AUC of PRL in
      AS patients (r = 0.46, p = 0.047), but not in the 2 control groups or in RA
      patients. CONCLUSION: Our results indicate no upregulated PRL or GH responses to
      stimulation in premenopausal women with RA or men with AS.

PMID- 15570645
TI  - Clinimetric evaluation of the bath ankylosing spondylitis metrology index in a
      controlled trial of pamidronate therapy.
AB  - OBJECTIVE: The Bath Ankylosing Spondylitis Metrology Index (BASMI) is an index
      comprising 5 measures of spinal and hip mobility in AS that has been primarily
      validated in the setting of a physiotherapeutic intervention and has not been
      validated in relation to functional outcomes. Our aim was to validate the BASMI
      and its individual components in relation to a validated functional index, the
      Bath AS Functional Index (BASFI), and to assess its responsiveness in patients
      with AS receiving 60 or 10 mg pamidronate monthly for 6 months in a double blind,
      randomized, controlled trial. METHODS: AS patients were assessed with the BASMI
      and BASFI at baseline and 6 months. Two versions of the BASMI were evaluated: the
      original scoring was based on a 0-2 score for each measure, while a newer version
      scores each measure on a 0-10 scale. Paired t tests, effect sizes (ES; mean
      difference divided by baseline standard deviation), and standardized response
      means (SRM; mean difference divided by standard deviation of the difference) were
      used to assess responsiveness. A value > 0.5 was considered to reflect good
      responsiveness. Responsiveness was also examined by linear regression analysis
      adjusting for age, sex, disease duration, and baseline Bath AS Disease Activity
      Index (BASDAI) and BASFI. The contribution of the BASMI to the variance in the
      BASFI was assessed by hierarchical linear regression analysis, independent
      variables being entered in the following order: (1) age, sex, disease duration;
      (2) drug dose group; (3) baseline or change in the BASDAI; and (4) change in the
      BASMI. Pearson correlation coefficient analysis was also performed to examine the
      contribution of individual measures of the BASMI. A value > 0.6 was defined as
      indicative of a good correlation. RESULTS: Seventy AS patients completed 6 months
      of therapy [81% male, mean age 40.3 yrs (SD 9.7), disease duration 15 yrs (SD
      9.5)]. The responsiveness of the BASMI was poor regardless of which version of
      the BASMI was used (ES = 0.26, SRM = 0.47 for the 60 mg dose group and using a 0
      10 scoring system). Examination of the responsiveness of the individual
      components of the BASMI revealed significance for lumbar side flexion in the 60
      mg dosing group (ES = 0.4, SRM = 0.43; p = 0.01) using the newer version of the
      BASMI (0-10 scoring) that was of similar responsiveness to the entire BASMI.
      Linear regression analysis showed no significant effects of age, sex, disease
      duration, baseline BASFI and BASDAI, or drug dose group on BASMI change scored
      using a 0-2 grading, but drug dose group had a significant effect on BASMI change
      scored using a 0-10 grading (p = 0.04). The correlation between changes in the
      BASMI and the BASFI was low, although significant when either version of the
      BASMI was examined (0.44 and 0.46 for the 0-2 and 0-10 scoring systems,
      respectively; p < 0.001). Of the individual components of the BASMI, a
      significant association was observed between changes in either cervical rotation
      or lumbar side flexion and changes in the BASFI (0.44 and 0.37, respectively; p <
      0.01). After adjusting for age, sex, disease duration, the baseline BASDAI, and
      drug dose group, the BASMI added significantly to the variance in the BASFI (p <
      0.001), but this was no longer significant once change in the BASDAI was added to
      the regression model. CONCLUSION: Responsiveness of the BASMI was poor with
      either scoring system. Lumbar side flexion was the most responsive of the BASMI
      components. Changes in the BASMI and its individual components did not correlate
      well with changes in functional outcomes.

PMID- 15570646
TI  - Colchicine for prophylaxis of acute flares when initiating allopurinol for
      chronic gouty arthritis.
AB  - OBJECTIVE: The use of colchicine to prevent acute gout flares during initiation
      of allopurinol therapy is widely practiced despite lack of proven benefit. We
      investigated if colchicine administration during initiation of allopurinol for
      chronic gouty arthritis reduces the frequency and/or severity of acute gout
      flares. METHODS: Patients starting allopurinol for crystal-proven chronic gouty
      arthritis were randomized to receive colchicine 0.6 mg po bid or placebo in a
      randomized, prospective, double blind, placebo controlled trial. Subjects were
      followed for evidence of acute gout flares and remained on study drug for 3
      months beyond attaining a serum urate concentration < 6.5 mg/dl. Treatment arms
      were analyzed regarding frequency of flares, likelihood of any flare or multiple
      flares, severity of flares on the visual analog scale (VAS), and length of flares
      in days. RESULTS: Forty-three subjects were studied. Subjects treated with
      colchicine experienced fewer total flares (0.52 vs 2.91, p = 0.008), fewer flares
      from 0 to 3 months (0.57 vs 1.91, p = 0.022), fewer flares 3-6 months (0 vs 1.05,
      p = 0.033), less severe flares as reported on VAS (3.64 vs 5.08, p = 0.018), and
      fewer recurrent gout flares (p = 0.001). Colchicine was well tolerated.
      CONCLUSION: Colchicine prophylaxis during initiation of allopurinol for chronic
      gouty arthritis reduces the frequency and severity of acute flares, and reduces
      the likelihood of recurrent flares. Treating patients with colchicine during
      initiation of allopurinol therapy for 6 months is supported by our data.

PMID- 15570647
TI  - Impact of osteoarthritis on quality of life in a Hong Kong Chinese population.
AB  - OBJECTIVE: To measure the impact of osteoarthritis (OA) on quality of life in the
      Hong Kong Chinese population. METHODS: This was a cross sectional, retrospective,
      non-random, cohort design stratifying disease severity and presence or absence of
      joint prostheses. Patients with OA (n = 574; 136 men and 438 women) were
      recruited from rheumatology, family medicine, orthopedics, and geriatric medicine
      clinics. They were divided into 2 equal groups based upon disease severity
      (either American College of Rheumatology functional classes I and II, or III and
      IV). The 36-item Medical Outcomes Study Short-Form Health Survey (SF-36) and
      Western Ontario and McMaster Universities (WOMAC) OA Index were used. RESULTS:
      Patients with severe disease had lower mean scores in all SF-36 domains and
      higher mean scores in all WOMAC domains, indicating poorer quality of life.
      Scores in patients who had had arthroplasty were better than those with severe
      disease only in certain domains: role physical, general health, vitality, and
      mental health (SF-36); and pain (WOMAC). Women with OA had poorer scores compared
      to men for bodily pain, general health, and mental health after adjusting for age
      and disease severity. Low educational attainment was independently associated
      with poorer scores when disease severity was taken into account. CONCLUSION: OA
      has a significant impact on quality of life, only partly ameliorated by
      arthroplasty, as assessed by the SF-36 and WOMAC in this population.

PMID- 15570648
TI  - Low prevalence of knee and back pain in southeast China; the Shantou COPCORD
      study.
AB  - OBJECTIVE: To determine whether the previously noted low prevalence of knee pain
      (KP) and lumbar pain (LP) in rural southern China compared with the high
      prevalence observed in North China was also true in a southern urban population.
      METHODS: A population based sample of 2040 adults > or = 16 years of age was
      studied in Chenghai City, close to the rural area previously studied on the
      southeast coast of China. Primary healthcare workers administered the COPCORD
      Phase I and II questionnaires. Those with rheumatic symptoms were recalled for
      medical examination, with a response rate at examination (phase III) of 98.4%.
      Those suspected of having arthritis had radiographs and laboratory tests.
      Prevalences were age and sex adjusted to the total of populations previously
      reported. RESULTS: (1) The prevalence for all rheumatic symptoms at phase III was
      18.1%. Of the 7.5% with KP, 55% had osteoarthritic changes on radiograph (KOA)
      compared with 29% of a sample with no KP (p < 0.001). Of the 11.5% with LP, 69%
      had degenerative changes on lumbar spine radiograph (LOA). (2) Of residents in
      single-level houses the prevalence was 5.6% for KP and 7.9% for LP, whereas in 4
      to 6-level apartment buildings these rates were significantly higher, 9.1% and
      16.2%, respectively. All these pain rates were significantly lower than noted in
      rural North China. The prevalence of pain together with radiographic OA changes
      in the knee (KOA) was half the rate in single-floor residents (2.7%) compared to
      apartment residents (5.3%), as was lumbar spine degenerative disease (5.3% vs
      11.5%). CONCLUSION: The prevalence of knee and lumbar spine pain in this southern
      urban sample was confirmed to be much lower than in the rural sample in the
      North, although higher than in the rural sample in the South. Comparing COPCORD
      studies of Han Chinese in Shanghai and Malaysia there was a decrease in
      prevalence of knee and back pain with latitude, suggesting an association with
      climate. Knee and back pain and radiological degenerative changes in the knee and
      lumbar spine were twice as prevalent in apartment residents than in those living
      in older single-level houses. Further study is needed to explain these
      observations.

PMID- 15570649
TI  - Slice thickness in the assessment of medial and lateral tibial cartilage volume
      and accuracy for the measurement of change in a longitudinal study.
AB  - OBJECTIVE: The optimal magnetic resonance image (MRI) slice thickness required to
      assess cartilage volume accurately and efficiently in cross-sectional and
      longitudinal studies is unknown. We compared cartilage volume measured from MRI
      of the knees using different slice thicknesses (1.5 to 7.5 mm) and assessed
      longitudinal change. METHODS: A total of 123 subjects with osteoarthritis had
      baseline and followup MRI on their symptomatic knee at 2 years. Medial and
      lateral tibial cartilage volumes were calculated using increasing slice thickness
      by extracting each second, third, fourth, or fifth slice area to calculate total
      volume, which was compared to the "gold standard" volume calculated from the
      original 1.5 mm slices. RESULTS: There was little difference in the average
      medial and lateral tibial cartilage volume observed as the slice thickness
      increased from 1.5 to 7.5 mm; medial tibial cartilage volume ranged from 1750
      microl to 1787 microl and lateral tibial cartilage volume ranged from 1949 microl
      to 2007 microl. There was also little absolute difference in the average change
      in medial and lateral tibial cartilage volume measured over 2 years. However,
      with increasing slice thickness, there was a decreased correlation between the
      tibial cartilage volume change calculated from the increased slice thickness,
      with the lowest correlation being 0.77 (p < 0.001) when the lateral cartilage
      volume calculated from the 7.5 mm slice was compared to the 1.5 mm slices.
      CONCLUSION: Increasing slice thickness may provide sufficiently accurate
      measurement of tibial cartilage volume and change over time in some studies. This
      would result in reduction in MRI scanning and postimaging processing time, which
      has the potential of increasing the feasibility of this technique.

PMID- 15570650
TI  - Undersulfated chondroitin sulfate does not increase in osteoarthritic cartilage.
AB  - OBJECTIVE: To test whether there is undersulfation of chondroitin sulfate in
      osteoarthritic bovine articular cartilage to support the hypothesis that sulfate
      deficiency is involved with the development of osteoarthritis. METHODS: Cartilage
      samples from bovine patellae (n = 32) were divided into 3 groups based on their
      osteoarthritic progression, as assessed by modified Mankin score. Uronic acid
      contents of the samples were determined. Fragmentation of the proteoglycans due
      to proteolytic processing was estimated with agarose gel electrophoresis. The
      molar ratios of chondroitin sulfate isoforms in the extracted proteoglycans were
      determined with fluorophore-assisted carbohydrate electrophoresis. RESULTS: Loss
      of proteoglycans and accumulation of tissue water was evident in groups II and
      III, and progressive OA increased heterogeneity of aggrecan population in groups
      II and III. Importantly, the molar ratio of nonsulfated disaccharide was
      decreased in the osteoarthritic articular cartilage. CONCLUSION: The structure of
      chondroitin sulfate in degenerated bovine cartilage did not support the
      hypothesis that sulfate depletion is present in osteoarthritic joint.

PMID- 15570651
TI  - Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets
      (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient,
      randomized, double blind, placebo controlled trial.
AB  - OBJECTIVE: To evaluate the analgesic efficacy and safety of tramadol 37.5
      mg/acetaminophen 325 mg (tramadol/APAP) combination tablets for treatment of
      chronic low back pain (LBP). METHODS: This 91 day, multicenter, outpatient,
      randomized, double blind, placebo controlled study enrolled 338 patients with
      chronic LBP requiring daily medication for > or = 3 months. Patients with at
      least moderate pain [pain visual analog scale (VAS) with scores > or = 40/100 mm]
      after washout were randomized to tramadol/APAP or placebo. After a 10 day
      titration, patients received 1 or 2 tablets QID. Primary outcome measure was
      final pain VAS score. Secondary measures included pain relief, quality of life
      and physical functioning, efficacy failure, and overall medication assessments.
      RESULTS: In total, 336 intent-to-treat patients received tramadol/APAP (n = 167)
      or placebo (n = 169). Mean baseline pain VAS score was 67.8. Intent-to-treat
      analysis showed significantly better mean final pain VAS scores (47.4 vs 62.9; p
      < 0.001) and mean final pain relief scores (1.8 vs 0.7; p < 0.001) for
      tramadol/APAP than for placebo. Roland Disability Questionnaire scores and
      physical-related subcategories of the McGill Pain Questionnaire and the Medical
      Outcome Study Short Form-36 Health Survey were significantly better for
      tramadol/APAP patients. More patients rated tramadol/APAP as "very good" or
      "good" than placebo (63.6 vs 25.2%; p < 0.001). Kaplan-Meier estimates of
      cumulative discontinuation rates due to efficacy failures were 22.9%
      (tramadol/APAP) vs 54.7% (placebo; p < 0.001). The most common treatment related
      adverse events with tramadol/APAP were nausea (12.0%), dizziness (10.8%), and
      constipation (10.2%). Average daily dose of tramadol/APAP was 4.2 tablets
      (tramadol 158 mg/APAP 1369 mg). CONCLUSION: Tramadol 37.5 mg/APAP 325 mg
      combination tablets show efficacy in pain reduction, in measures of physical
      functioning and quality of life, and in overall medication assessments, with a
      tolerability profile comparable with other opioids used for the treatment of
      chronic LBP.

PMID- 15570652
TI  - Fibromyalgia in men: comparison of psychological features with women.
AB  - OBJECTIVE: To describe possible differences in psychological factors in men
      compared to women with fibromyalgia syndrome (FM). METHODS: Forty men and 160
      women with FM were evaluated for anxiety, stress, and depression measured by
      ordinal scales and validated psychological instruments. Clinical and
      psychological variables were evaluated by a protocol. RESULTS: Both men and women
      scored high in the psychological variables measured but the results were not
      significantly different between them. CONCLUSION: There was no significant
      difference between men and women with FM in their psychological status.

PMID- 15570653
TI  - Is there benefit in referring patients with fibromyalgia to a specialist clinic?
AB  - OBJECTIVE: To examine the benefit of specialist rheumatology consultation and
      followup for the first 238 patients referred to a tertiary care fibromyalgia (FM)
      clinic with emphasis on final diagnosis and outcome. METHODS: A retrospective
      chart review was performed for the first 238 patients attending a rheumatology
      subspecialty FM clinic. The main variables of interest were management received
      at the clinic, final diagnosis, and outcome. RESULTS: The final diagnosis was FM
      in 68%, and some other condition in the remaining 32%. Specialist contact was
      identified as useful in 73% of the total patient group, 96 with FM and 74 with
      non-FM. In the patients with FM who received followup in the clinic, outcome was
      judged favorable in 54%, whereas 46% showed no change or decline in health
      status. CONCLUSION: An important value of specialist rheumatology contact for
      patients with a symptom suggestive of diffuse musculoskeletal pain is to ensure
      that some other potentially treatable condition is not overlooked, rather than
      the provision of ongoing care for those with FM. Continued followup in a
      specialist clinic for patients with a primary diagnosis of FM is of questionable
      benefit.

PMID- 15570654
TI  - The Short Arthritis Assessment Scale: a brief assessment questionnaire for rapid
      evaluation of arthritis severity in research and clinical practice.
AB  - OBJECTIVE: To develop a short, 4-item arthritis severity questionnaire that is
      simple to score, clinically useful and meaningful, and suitable for use in
      primary care, where osteoarthritis (OA) is the primary prevalent arthritis
      illness. METHODS: Data and items from the Medical Outcomes Study Short Form 36
      (SF-36), the Western Ontario McMaster Osteoarthritis Index (WOMAC(c)), and visual
      analog scales (VAS) for pain and patient global severity were studied in 16,519
      patients with arthritis. The Short Arthritis Assessment Scale (SAS) was developed
      by performing multivariable analyses that involved individually
      adding/subtracting items in differing regression models. The candidate items and
      scales were then studied by Rasch analysis, and tested for effect size,
      sensitivity to change, and reliability. The resultant scale was validated using
      data from a recent OA clinical trial. RESULTS: The VAS pain and VAS global
      severity scales and 2 items from the WOMAC in the VAS format, difficulty going
      down stairs and difficulty shopping, were found to be the best predictors of
      change in health status. The 4-item SAS was reliable (Cronbach's alpha = 0.87),
      demonstrated good test-retest reliability (Lin's concordance coefficient = 0.85),
      was unidimensional, and was strongly correlated with other important clinical
      measures, indicating good construct validity. Using data from a recent randomized
      clinical trial in OA, the SAS performed better than the WOMAC pain scale and the
      SF-36 physical component score in detecting change, and at least as well as the
      clinical trial VAS pain scale. CONCLUSION: The SAS is a 4-item arthritis severity
      questionnaire that can be easily administered in primary care for patients with
      OA, but is suitable for use across all arthritis illnesses. Scoring is simple,
      requiring only the addition of four 10-point scales, and interpretation is
      straightforward. The SAS may have a role in rapid assessment of the arthritis
      patient in primary care practice.

PMID- 15570655
TI  - Anti-52 kDa Ro, anti-60 kDa Ro, and anti-La antibody profiles in neonatal lupus.
AB  - OBJECTIVE: Studies suggest that anti-52 kDa Ro antibodies are more sensitive and
      specific than anti-60 kDa Ro antibodies for neonatal lupus. However, these
      studies mainly used immunoblot or ELISA using recombinant protein, which have
      poor sensitivity for anti-60 kDa Ro antibodies. In addition, the control patients
      were not disease matched. We reassessed the sensitivity and specificity of anti
      52 kDa Ro, anti-60 kDa Ro, and anti-La, addressing these limitations. METHODS AND
      RESULTS: To assess sensitivity, 125 mothers of children with neonatal lupus (NLM)
      were recruited. All maternal sera were assessed using a commercial line
      immunoassay that uses natural 60 kDa Ro protein (Inno-Lia ANA Update,
      Innogenetics NV, Gent, Belgium). By this method, 96% of the sera had antibodies
      to 60 kDa Ro, 86% to 52 kDa Ro, and 78% to 48 kDa La. Immunoblot of 65 NLM showed
      significantly fewer positive results for anti-60 kDa Ro (p < 0.001) and anti-52
      kDa Ro (p < 0.05). Sensitivity of the 3 antibodies was assessed in the
      symptomatic mothers of children with congenital heart block (CHB) (78 women) and
      disease matched controls with unaffected children (65 women) using Inno-Lia ANA
      Update. The sensitivity of each antibody was compared by multiple logistic
      regression to adjust for maternal disease. There was no significant difference
      between the groups for 60 kDa Ro or for anti-52 kDa Ro antibody. However, there
      was a significant difference for the anti-La antibody (p = 0.001), with an odds
      ratio of 3.59. This translates to an increase in risk from a published 2% for CHB
      in an anti-Ro-positive mother to 3.1% if the woman is also anti-La antibody
      positive, and to a decrease in risk to 0.9% if anti-La-negative. CONCLUSION:
      Contrary to previous reports, 52 kDa Ro as detected by Inno-Lia ANA Update is not
      more specific for or frequent in CHB than 60 kDa Ro. However, the presence of
      anti-La antibodies significantly increases the risk for CHB.

PMID- 15570656
TI  - The juvenile arthritis foot disability index: development and evaluation of
      measurement properties.
AB  - OBJECTIVE: To develop a new juvenile arthritis foot disability index (JAFI) and
      to test it for validity and reliability. METHODS: Samples of 14
      children/adolescents and 30 children/adolescents with juvenile idiopathic
      arthritis (JIA) and 29 healthy children/adolescents participated. We used a
      questionnaire derived from the International Classification of Functioning,
      Disability and Health that included 27 statements divided into the dimensions
      Impairment, Activity Limitation, and Participation Restriction. Comments on the
      contents were invited from parents and adolescents. Convergent and divergent
      construct validity was examined by comparing the 3 JAFI dimensions to joint
      impairment scores, the Childhood Health Assessment Questionnaire (CHAQ), and self
      rated, foot-related participation restriction. Known groups construct validity
      was assessed by comparing answers from children with JIA to those from healthy
      children. Test-retest stability was investigated over one week. RESULTS: One item
      was added after suggestions from 2 participants. A consistent pattern of
      increasing JAFI scores was found with increasing joint impairment scores, CHAQ
      scores, and self-rated foot-related participation restriction. Foot-related
      disability as assessed by JAFI was more pronounced in children with JIA than in
      healthy controls. One statement showing a floor effect was excluded. No internal
      redundancy (rs > 0.90) between items was found, and internal consistency within
      each subscale was satisfactory (rs > 0.50) for all items but one. No systematic
      differences were found between test and retest, and weighted kappa coefficients
      for the 3 JAFI dimensions were 0.90, 0.85, and 0.88. CONCLUSION: The JAFI appears
      to be valid and reliable for assessing foot-related disability among
      children/adolescents with JIA. Its sensitivity to change remains to be
      investigated.

PMID- 15570657
TI  - The PedsQL Multidimensional Fatigue Scale in pediatric rheumatology: reliability
      and validity.
AB  - OBJECTIVE: . The PedsQL (Pediatric Quality of Life Inventory) is a modular
      instrument designed to measure health related quality of life (HRQOL) in children
      and adolescents ages 2-18 years. The recently developed 18-item PedsQL
      Multidimensional Fatigue Scale was designed to measure fatigue in pediatric
      patients and comprises the General Fatigue Scale (6 items), Sleep/Rest Fatigue
      Scale (6 items), and Cognitive Fatigue Scale (6 items). The PedsQL 4.0 Generic
      Core Scales were developed as the generic core measure to be integrated with the
      PedsQL Disease-Specific Modules. The PedsQL 3.0 Rheumatology Module was designed
      to measure pediatric rheumatology-specific HRQOL. Methods. The PedsQL
      Multidimensional Fatigue Scale, Generic Core Scales, and Rheumatology Module were
      administered to 163 children and 154 parents (183 families accrued overall)
      recruited from a pediatric rheumatology clinic. Results. Internal consistency
      reliability for the PedsQL Multidimensional Fatigue Scale Total Score (a = 0.95
      child, 0.95 parent report), General Fatigue Scale (a = 0.93 child, 0.92 parent),
      Sleep/Rest Fatigue Scale (a = 0.88 child, 0.90 parent), and Cognitive Fatigue
      Scale (a = 0.93 child, 0.96 parent) were excellent for group and individual
      comparisons. The validity of the PedsQL Multidimensional Fatigue Scale was
      confirmed through hypothesized intercorrelations with dimensions of generic and
      rheumatology-specific HRQOL. The PedsQL Multidimensional Fatigue Scale
      distinguished between healthy children and children with rheumatic diseases as a
      group, and was associated with greater disease severity. Children with
      fibromyalgia manifested greater fatigue than children with other rheumatic
      diseases. CONCLUSION: The results confirm the initial reliability and validity of
      the PedsQL Multidimensional Fatigue Scale in pediatric rheumatology.

PMID- 15570658
TI  - Guidelines for blood test monitoring of methotrexate toxicity in juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To assess the utility of the American College of Rheumatology
      guidelines for monitoring methotrexate (MTX)-related toxicity in a cohort of
      children with juvenile idiopathic arthritis (JIA). METHODS: Eighty-nine patients
      with JIA treated with MTX were monitored prospectively: aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), complete blood count
      (CBC), and differential blood count were measured prior to starting MTX, and then
      monthly. Significantly abnormal blood tests (SABT) were prospectively defined as
      (1) significantly elevated liver enzymes (SELE) greater than twice the upper
      limit of normal; (2) granulocyte count < 1.5 109/l; (3) lymphocyte count < 0.9
      109/l; or (4) hemoglobin decreased by > 2 g/l from previous level. Clinical
      interventions, current and cumulative MTX dose, duration of treatment,
      comorbidity, and concurrent medications at the time of the first SABT
      identification were recorded. Independent t tests and chi-squared tests were used
      for comparisons, and the probability of developing a SABT was calculated by
      Kaplan-Meier survival analysis. RESULTS: Forty percent of patients had a SABT:
      26% had hematological abnormalities and 14% had SELE. Ninety-five percent of
      patients with SABT had symptoms consistent with a viral infection when the SABT
      was drawn and MTX dose was withheld until results had normalized on repeat
      testing. SABT persisting beyond one month occurred in only 2 patients, and their
      abnormalities resolved by 6 months with no specific identified cause; they
      resumed MTX at a later time without recurrence of SABT. There were no differences
      between patients with and without SABT with respect to current or cumulative MTX
      dose, duration of treatment, and concurrent medications at the time of the SABT.
      The probability of developing a SABT was estimated to be 11% at 3 months,
      compared to 10% probability of having an abnormal blood test by chance alone.
      CONCLUSION: Routine blood tests every 4 to 8 weeks in children with JIA are
      unnecessarily frequent.

PMID- 15570659
TI  - Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and
      triamcinolone acetonide in treatment of juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To compare patients with juvenile rheumatoid arthritis (JRA) injected
      with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA) with respect
      to time to relapse. METHODS: This was a retrospective chart review of 85
      patients: 51 patients with JRA who had received a joint injection with TH during
      the period June 2000-April 2001 and 48 patients who had received a joint
      injection with TA during the period May 2001-March 2002 who were followed for a
      minimum of 15 months, after an intraarticular steroid injection. RESULTS: The
      primary endpoint variable for the study was the time to relapse of the arthritis
      in the affected joint following an intraarticular injection. A total of 227
      joints were injected, 114 with TH and 113 with TA. In the TH group the mean time
      to relapse (+/- SE) was 10.14 +/- 0.49 months compared to the TA group at 7.75 +/
      0.49 months (p < 0.0001) using the log-rank test. A proportional hazards (Cox)
      regression analysis revealed no statistical association between sex, duration of
      illness, or type of arthritis and relapse time. An analysis was performed on the
      first intraarticular injection for each patient, with the average time to relapse
      for all joints injected of 10.36 +/- 0.72 months for TH compared to 8.45 +/- 0.78
      months for TA (p < 0.02). A further analysis of the first knee injections showed
      a relapse time in the TH group of 11.11 +/- 0.81 months compared to 7.95 +/- 0.95
      months for TA (p < 0.008). CONCLUSION: TH offers an advantage to TA, as there is
      a longer duration of action leading to an improved prolonged response rate in
      weight-bearing joints, particularly the knees. The results suggest that TH should
      be the intraarticular steroid of choice, particularly for the knee joint, in
      patients with JRA.

PMID- 15570660
TI  - Nonmyeloablative stem cell transplant in a patient with advanced systemic
      sclerosis and systemic lupus erythematosus.
AB  - Systemic sclerosis (SSc) is an uncommon connective tissue disease characterized
      by excessive collagen deposition within the skin and internal organs. Most
      patients with diffuse severe SSc are treated with immunosuppressive agents, but
      patients with advanced disease have very high 5-year mortality rates despite
      adequate therapy. We describe a patient with both diffuse cutaneous SSc and
      systemic lupus erythematosus who showed mixed chimerism 29 months after
      undergoing nonmyeloablative stem cell transplant. She experienced remission of
      both diseases.

PMID- 15570661
TI  - Disseminated primary varicella infection during infliximab treatment.
AB  - A young man developed a serious disseminated varicella infection, necessitating
      antiviral treatment, after being treated with anti-tumor necrosis factor-alpha
      therapy for rheumatoid arthritis.

PMID- 15570662
TI  - Two familial cases with tumor necrosis factor receptor-associated periodic
      syndrome caused by a non-cysteine mutation (T50M) in the TNFRSF1A gene associated
      with severe multiorganic amyloidosis.
AB  - An adolescent boy had had recurrent episodes of fever, abdominal pain, and
      arthralgias since the age of 7 years. Progressive renal failure due to renal
      amyloidosis developed, leading to renal transplant at the age of 14.5 years. Five
      years later, he developed AA amyloidosis in the transplant as well as the thyroid
      gland. His father had had similar symptoms including systemic amyloidosis since
      the age of 6 years. DNA sequence analysis revealed a heterozygous mutation in the
      TNFRSF1A (TNFa-receptor 1) gene (T50M) in both father and son causing tumor
      necrosis factor receptor-associated periodic syndrome (TRAPS). Previous
      phenotype/genotype analyses have proposed that this mutation is usually not
      associated with the occurrence of amyloidosis. This difference in the clinical
      course in different families may indicate a strong influence of modifier genes.
      Treatment with a TNFRSF1B fusion protein TNF antagonist (etanercept) favorably
      influenced the disease course.

PMID- 15570663
TI  - Tenosynovitis of the Hands Caused by Mycobacterium kansasii in a patient with
      scleroderma.

PMID- 15570664
TI  - Swallowing difficulties from "DISH-phagia".

PMID- 15570666
TI  - Is the STAR trial really a safety trial?

PMID- 15570667
TI  - Niacin-like reaction to infliximab infusion in systemic juvenile rheumatoid
      arthritis.

PMID- 15570668
TI  - Suggestion for working with chemically dependent women who wish to breastfeed.

PMID- 15570669
TI  - Mortality among patients with HIV infection in the HAART era.

PMID- 15570670
TI  - Postexposure prophylaxis for nonoccupational HIV exposure.

PMID- 15570671
TI  - The K65R mutation: selection, frequency, and possible consequences.

PMID- 15570672
TI  - AIDS-related non-Hodgkin lymphoma: still a problem in the era of HAART.
AB  - Despite advances in HAART, patients with HIV infection remain at significantly
      increased risk for intermediate- and high-grade B-cell non-Hodgkin lymphoma. The
      reasons for this persistent risk and the clinical and molecular correlates that
      predict outcomes and treatment responsiveness are areas of active investigation.
      Here we review the epidemiologic and pathobiologic features of AIDS-related
      lymphoma along with clinical evaluation and treatment options in patients with
      this disease.

PMID- 15570673
TI  - Primary care guidelines for persons infected with HIV.

PMID- 15570674
TI  - Progress report on new antiepileptic drugs: a summary of the Seventh Eilat
      Conference (EILAT VII).
AB  - The Seventh Eilat Conference on New Antiepileptic Drugs (AEDs) (EILAT VII) took
      place in Villasimius, Sardinia, Italy from the 9th to 13th May 2004. Basic
      scientists, clinical pharmacologists and neurologists from 24 countries attended
      the conference,whose main themes included advances in pathophysiology of drug
      resistance, new AEDs in pediatric epilepsy syndromes, modes of AED action and
      spectrum of adverse effects and a re-appraisal of comparative responses to AED
      combinations. Consistent with previous formats of this conference, the central
      part of the conference was devoted to a review of AEDs in development, as well as
      updates on second-generation AEDs. This article summarizes the information
      presented on drugs in development, including atipamezole, BIA-2-093,
      fluorofelbamate, NPS 1776, pregabalin, retigabine, safinamide, SPM 927,
      stiripentol, talampanel,ucb 34714 and valrocemide (TV 1901). Updates on
      felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine,
      tiagabine,topiramate, vigabatrin, zonisamide, new oral and parenteral
      formulations of valproic acid and SPM 927 and the antiepileptic vagal stimulator
      device are also presented.

PMID- 15570675
TI  - Drug labeling; sodium labeling for over-the-counter drugs. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule amending the
      regulations for sodium labeling for over-the-counter (OTC) drug products by
      extending the sodium content labeling requirement to rectal drug products
      containing sodium phosphate/sodium biphosphate (sodium phosphates). FDA is taking
      this action because people with certain medical conditions are at risk for an
      electrolyte imbalance to occur when using rectal sodium phosphates products.
      Serious adverse events and deaths have occurred because of the high level of
      sodium present in these products. This final rule is part of FDA's ongoing review
      of OTC drug products.

PMID- 15570676
TI  - Patient autonomy versus religious freedom: should state legislatures require
      Catholic hospitals to provide emergency contraception to rape victims?

PMID- 15570677
TI  - Patent first, ask questions later: morality and biotechnology in patent law.
AB  - This Article explores the U.S. "patent first, ask questions later" approach to
      determining what subject matter should receive patent protection. Under this
      approach, the U.S. Patent and Trademark Office (USPTO or the Agency) issues
      patents on "anything under the sun made by man," and to the extent a patent's
      subject matter is sufficiently controversial, Congress acts retrospectively in
      assessing whether patents should issue on such interventions. This practice has
      important ramifications for morally controversial biotechnology patents
      specifically, and for American society generally. For many years a judicially
      created "moral utility" doctrine served as a type of gatekeeper of patent subject
      matter eligibility. The doctrine allowed both the USTPO and courts to deny
      patents on morally controversial subject matter under the fiction that such
      inventions were not "useful." The gate, however, is currently untended. A
      combination of the demise of the moral utility doctrine, along with expansive
      judicial interpretations of the scope of patent-eligible subject matter, has
      resulted in virtually no basis on which the USTPO or courts can deny patent
      protection to morally controversial, but otherwise patentable, subject matter.
      This is so despite position statements by the Agency to the contrary.
      Biotechnology is an area in which many morally controversial inventions are
      generated. Congress has been in react-mode following the issuance of a stream of
      morally controversial biotech patents, including patents on transgenic animals,
      surgical methods, and methods of cloning humans. With no statutory limits on
      patent eligibility, and with myriad concerns complicating congressional action
      following a patent's issuance, it is not Congress, the representative of the
      people, determining patent eligibility. Instead, it is patent applicants,
      scientific inventors, who are deciding matters of high public policy through the
      contents of the applications they file with the USTPO. This Article explores how
      the United States has come to be in this position, exposes latent problems with
      the "patent first" approach, and considers the benefits and disadvantages of the
      "ask questions first, patents later" approaches employed by some other countries.
      The Article concludes that granting patents on morally controversial biotech
      subject matter and then asking whether such inventions should be patentable is
      bad policy for the United States and its patent system, and posits workable,
      proactive ways for Congress to successfully guard the patent-eligibility gate.

PMID- 15570678
TI  - A little off the top. Neb. system to trim leadership to help doc relations.

PMID- 15570679
TI  - Ethnicity, education, and the cortisol response to awakening: a preliminary
      investigation.
AB  - OBJECTIVE: To explore the associations among ethnicity, educational attainment,
      and cortisol secretion. DESIGN: Participants include 63 white (n = 31) and
      African-American (n = 32) adult men and women. Subjects provided salivary
      cortisol samples immediately upon awakening and again, 30 minutes later. RESULTS:
      Analyses adjusted for relevant covariates revealed a steeper awakening response
      among whites with higher education compared to other groups. Cortisol levels were
      significantly lower among African-American participants with lower levels of
      education. All effects were independent of perceived stress. CONCLUSIONS: These
      preliminary findings demonstrate significant ethnic and education-related
      differences in awakening cortisol secretion responses. Our data highlight the
      importance of considering ethnicity and the moderating effects of social class
      when examining the associations among social contextual factors and cortisol
      secretion.

PMID- 15570680
TI  - Factors influencing food choices, dietary intake, and nutrition-related attitudes
      among African Americans: application of a culturally sensitive model.
AB  - OBJECTIVES: The goals of the project were: (1) to explore how culture and
      community impact on the nutrition attitudes, food choices, and dietary intake of
      a selected group of African Americans in north central Florida; and (2) to
      identify segments of the population and community that should be targeted for
      education programs, desirable components of nutrition education programs, topics
      of interest, and health promotion channels to reach the target group. DESIGN: Six
      focus groups were conducted with African American males and females. The data
      were analyzed using the PEN-3 model, a theoretical model that centralizes culture
      as the primary reason for health behavior and the primary consideration for
      health promotion and diseases prevention programs. RESULTS: There was a general
      perception that 'eating healthfully' meant giving up part of their cultural
      heritage and trying to conform to the dominant culture. Friends and relatives
      usually are not supportive of dietary changes. Barriers to eating a healthful
      diet also included no sense of urgency, the social and cultural symbolism of
      certain foods, the poor taste of 'healthy' foods, the expense of 'healthy' foods,
      and lack of information. Segments of the population that potentially could be
      motivated to make dietary changes included women, men with health problems, young
      adults, the elderly, and those diagnosed with a severe, life-threatening disease.
      CONCLUSION: The findings suggest that the PEN-3 model is an appropriate framework
      for assessing how community and culture impact dietary habits of African
      Americans. African Americans will need information on basic nutrition topics such
      as serving sizes and reading food labels. The findings also suggest that programs
      and materials should be specifically developed for churches, neighborhood grocery
      stores, and local restaurants.

PMID- 15570681
TI  - Stressful life events, smoking behavior, and intentions to smoke among and
      multiethnic sample of sixth graders.
AB  - OBJECTIVES: Adolescent smoking has been associated with stressful life events.
      However, few studies have examined the associations between stress, smoking
      intentions, and smoking behavior among a multiethnic sample of adolescents.
      METHODS: We compiled a checklist of stressful life events relevant to multiethnic
      youth and administered it to 1,074 sixth-grade students in urban Los Angeles.
      RESULTS: The most frequently reported stressful events were similar across ethnic
      groups and generations in the USA: test taking, chores, and arguments with
      friends. The events reported as the most severe were disturbances in family life,
      such as: death, arguments between parents, and illness or injury. Whites and
      Latinos had reported higher levels of ever smoking and intentions to smoke than
      Asian/Pacific Islanders (PIs). On the positive family-related events scale
      Latinos scored higher than did whites or Asian/PIs. Whites scored higher than
      Latinos or Asian/PIs on both negative peer-related and negative personal-related
      events. Associations were observed between total stress, stressful life events,
      and smoking behavior and intentions to smoke. Total stress was associated ith
      ever smokers, smoking intentions within the next year and in high school over the
      entire sample. Negative peer-related events were associated with intention to
      smoke within the next year, among Latinos. Among Asian/PIs negative peer-related
      events were associated with intention to smoke within the next year and in high
      school. Negative school-related events were significantly associated with ever
      smoking and intentions to smoke in the next year and marginally associated with
      intentions to smoke in high school among children born in the USA whose parents
      were also born in the USA. Negative peer-related events and positive personal
      related events were significantly associated with intentions to smoke in the next
      year among children born in the USA whose parents were immigrants. CONCLUSIONS:
      Results suggest that negative peer- and school-related events may lead to
      increased risk of smoking behavior and intentions to smoke among multicultural
      adolescents.

PMID- 15570682
TI  - Peginterferon plus ribavirin for hepatitis C in HIV-infected patients.

PMID- 15570683
TI  - Methylprednisolone, valacyclovir, or both for vestibular neuritis.

PMID- 15570684
TI  - Methylprednisolone, valacyclovir, or both for vestibular neuritis.

PMID- 15570685
TI  - Treatment of von Willebrand's Disease.

PMID- 15570686
TI  - Acute renal failure and sepsis.

PMID- 15570687
TI  - Acute renal failure and sepsis.

PMID- 15570688
TI  - Acute renal failure and sepsis.

PMID- 15570689
TI  - Differential requirement for ptf1a in endocrine and exocrine lineages of
      developing zebrafish pancreas.
AB  - Mammalian studies have implicated important roles for the basic helix-loop-helix
      transcription factor Ptf1a-p48 in the development of both exocrine and endocrine
      pancreas. We have cloned the Ptf1a-p48 ortholog in Danio rerio. Early zebrafish
      ptf1a expression is observed in developing hindbrain and in endodermal pancreatic
      precursors. Analysis of ptf1a and insulin expression reveals a population of
      exocrine precursors that, throughout early development, are temporally and
      spatially segregated from endocrine elements. Morpholino-mediated knockdown of
      ptf1a confirms early divergence of these endocrine and exocrine lineages. Ptf1a
      morphants lack differentiated exocrine pancreas, but maintain normal
      differentiation and organization of the principal islet. In addition to the
      exocrine phenotype, ptf1a knockdown also reduces the prevalence of a small
      population of anterior endocrine cells normally found outside the principal
      islet. Together, these findings suggest the presence of distinct ptf1a-dependent
      and ptf1a-independent precursor populations in developing zebrafish pancreas.

PMID- 15570690
TI  - Mutagenic activity of sweepings and pigments from a household-wax factory assayed
      with Salmonella typhimurium.
AB  - The mutagenic activity of garbage originating from a household wax industry was
      determined by the Salmonella/microsome assay, using the bacterial strains TA100,
      TA98 and YG1024. The garbage was obtained by sweeping the floor of the factory at
      the end of the work shift. Organic compounds were extracted by ultrasound for 30
      min in dichloromethane or 70% ethanol. After evaporation of solvent, these
      extracts (HFS: household-wax factory sweepings) were dissolved in DMSO, and were
      tested for the mutagenic activity at varying concentrations (HFS-ET: 0.08-0.68
      mg/plate, HFS-DCM: 0.60-7.31 mg/plate). The colouring agents (pigments) used in
      the production of the wax were also dissolved in DMSO and tested with the assay.
      The concentrations tested for each pigment were: Amaranth: 0.46-3.65 mg/plate,
      Auramine: 0.15-1.2 mg/plate and Rhodamine B: 0.22-1.82 mg/plate. Both ET and DCM
      organic extracts had mutagenic activity, especially in the YG1024 strain. The
      pigments behaved in a similar way, demonstrating that YG1024 was the most
      sensitive strain for the detection of mutagenicity, and that metabolization
      increased the activity. Human exposure (occupational and non-occupational) to
      industrial residues generated during the household-wax manufacturing and
      packaging process should be monitored, since this type of garbage is normally
      deposited in the environment without any control.

PMID- 15570691
TI  - Merci retriever.

PMID- 15570692
TI  - Occupational therapist.

PMID- 15570693
TI  - Making Europe healthy.

PMID- 15570694
TI  - Electrifying European research.

PMID- 15570695
TI  - The Kozijavkin method.

PMID- 15570696
TI  - Profile: Staffan Hildebrand: film maker who charts the spread of AIDS.

PMID- 15570697
TI  - Proceedings of the International Conference on Advanced Laser Technology, Silsoe,
      United Kingdom, 19-23 September 2003.

PMID- 15570698
TI  - Cloning and sequence analysis of llama cytokines related to cell-mediated
      immunity.
AB  - In order to characterize the T helper 1 (Th1) cytokines of llama, we have cloned
      several llama cytokine genes and compared them to those of other mammalian
      species. The cDNAs encoding for interleukin (IL)-2, interferon (IFN), IL-12p35
      and IL-12p40 were amplified using specific primers designed from reported
      sequences of bovine cytokine genes. The cDNAs for llama IL-2, IFN-, IL-12 p35 and
      IL-12p40 were found to be 465, 501, 669 or 993 bp in length, with open reading
      frames encoding 154, 166, 222 or 330 amino acids, respectively. Homology analyses
      of nucleotide and deduced amino sequences of llama IL-2, IFN-, IL-12p35 and IL
      12p40 and phylogenetic analysis based on their nucleotide sequences indicated the
      close relationship in these cytokine genes between llama and eutherian mammalian
      order Artiodactyla, which includes pig and cattle.

PMID- 15570699
TI  - Abstracts of the XXXIII Conference of the National Society of Immunology, 18-20
      June 2003.

PMID- 15570701
TI  - Proceedings of the 27th International Symposium on High-Performance Liquid-Phase
      Separations and Related Techniques, Part III. Nice, France, 15-19 June 2003.

PMID- 15570700
TI  - Proceedings of the 27th International Symposium on High-Performance Liquid-Phase
      Separations and Related Techniques, Part 1. Nice, France, 15-19 June 2003.

PMID- 15570702
TI  - Sol Londe.

PMID- 15570703
TI  - Medical image. Flank football.

PMID- 15570704
TI  - [Prostate cancer. Epidemiology. Risk factors. Pathology].
AB  - Prostate cancer (prostate adenocarcinoma) has become an important concern in
      terms of public health these past fifteen years; recent French epidemiological
      data revealed 10,104 deaths due to this disease in 2000. The two main factors
      involved are the serum prostatic specific antigen (PSA), routinely used since
      late 1980's and which allows early diagnosis (before symptom onset), and the
      lengthened duration of life. Such cancer is rare before the age of 50, but its
      frequency increases with age, making it the most frequent type of cancer in
      French men. Although the aetiology of this disease is unknown, the ethnic origin,
      and a familial history of prostate or breast cancer are known risk factors.
      Predisposing genes to such hereditary types remain to be identified. Other
      genetic factors (polymorphisms), combined with environmental factors such as
      nutrition, have been incriminated, which is likely to explain the geographical
      variations of this affection. At the molecular level, the mechanisms involved in
      the tumoral initiation and progression remain unclear. Various genetic
      alterations have been identified among the genome of cancerous cells, at various
      stages of the affection: intraepithelial neoplasia, localized, locally advanced,
      metastatic or hormone refractory stage -, hormonal escape). However, the precise
      sequence and nature of the complex molecular events remain to be determined prior
      to their routine utilisation in the determination of subjects at risk, or as
      prognostic factors, and even as therapeutic targets. The anatomopathology is a
      key for the diagnosis. Intraepithelial neoplasia is the pre-cancerous lesion
      observed in most adenocarcinomas; these are localized in the peripheral part of
      the prostate gland in 70% of the cases. Gleason's classification is the current
      gold standard for the determination of tumoral aggressiveness and categorisation
      of the adenocarcinomas which are basically heterogeneous (coexistence of tumors
      cells with different degrees of differenciation in the same tumor). This
      anatomopathological classification allows distinguishing the tumours in terms of
      potential progressiveness and prognosis, and hence, to orientate the therapeutic
      strategy in case of localised or locally advanced prostate cancer.

PMID- 15570705
TI  - [Prostate cancer: Diagnosis and staging].
AB  - The discovery and the use of serum prostate specific antigen (PSA) has
      considerably improved the diagnosis of prostate cancer during the past 20 years.
      Before PSA era, early diagnosis was only based on the digital rectal examination
      (DRE) of which the Limitations have been evidenced; over half of the tumours
      diagnosed by such means had already spread out of the prostate and were
      incurable. Assessment of serum PSA has allowed the diagnosis to be made at an
      earlier stage of the disease, curable by current treatments. Whichever the
      diagnostic tools, transrectal ultrasound (TRUS) prostatic biopsies remain
      necessary for diagnosis ascertainment, taking into account the low specificity of
      PSA assessment. The feasibility of a diagnosis at an early and curable stage of
      the disease has logically resulted in screening procedures aimed at reducing the
      high mortality related to prostate cancer. The numerous publications on prostate
      cancer screening provide precise information on the accuracy of available
      diagnostic means (PSA, DRE, TRUS, combined PSA and DRE), on the characteristics
      of screened tumours (stage and differentiation), and also on the population of
      men likely to benefit from the screening (age at beginning and end of the
      screening, frequency of PSA testing, identification of the men with ethnic and/or
      genetic predisposition). In those early diagnosed prostate cancers, the
      assessment of loco-regional cancer extension (extracapsular and/or, microscopic
      nodal involvement), remains unsatisfactory because no imaging technique
      (ultrasonography, CT scan, MRI,...) allows visualising the tumour itself or
      microscopic metastases. Nevertheless, the combination of multiple parameters such
      as DRE data, PSA level, biopsy data and tumour differentiation helps approaching
      with an increasing precision (nomograms) the true pathologic stage of the
      disease. Such advances allow distinguishing, among the very heterogeneous group
      of prostate cancers, tumours that differ from one to another in terms of disease
      stage, progression and prognosis, which is helpful for the determination of an
      adapted therapeutic strategy.

PMID- 15570706
TI  - [Prostate cancer. Treatment].
AB  - The discovery and the utilisation of the prostate specific antigen (PSA) that
      allows early diagnosis of prostate cancer, have considerably improved the
      management of this disease. Before the PSA era, prostate cancer was just a
      disease of the old man, generally detected at an advanced stage and incurable,
      with a fatal outcome delayed by the androgenic deprivation. Since early 1990's,
      prostate cancer has become primarily a disease of the man of 60 years, detectable
      earlier, and curable provided no extraprostatic dissemination has occurred. Early
      treatment of prostate cancer has benefited from important advances in surgical
      and radio-therapeutic techniques (conformational irradiation, brachytherapy),
      with, as principal goal, the combination of a better survival and the reduction
      of the potential adverse effects that alter quality of life. A better definition
      of the characteristics of the tumours in terms of progression regarding various
      parameters (clinical stage, PSA, tumoral differentiation) have resulted, despite
      the heterogeneity of the disease, in the determination of subgroups of tumours
      with different prognosis, which leads to an improved therapeutic strategy. The
      assessment of men's life expectancy (< or > 10 years) is the second primary
      parameter on which is based the indication for curative or non curative therapy
      in case of localized tumour. Roughly, before the age of 75, a curative therapy is
      indicated whereas after this age a surveillance is reasonable as first-line
      treatment, followed by hormone therapy in case of onset of symptoms indicating
      some progression of the disease (urinary symptoms, bone lesion). At a Later
      stage, in case of a metastatic or locally advanced cancer, hormone therapy by
      androgenic deprivation is highly indicated. The hormone sensitivity characterizes
      prostate cancer; it has been discovered more than 50 years ago by Charles Huggins
      (Nobel prize-winner). This hormone therapy is a palliative treatment since its
      efficacy is transient (ineluctable occurrence of hormone resistance in a variable
      time delay), but it constitutes an essential therapeutic means with a well
      established efficacy. Hormone therapy has progressively improved, with the
      renunciation of oestrogen therapy and surgical castration which has been replaced
      by luteinizing hormone-releasing hormone (LH-RH) analogues, and/ or anti
      androgens. Numerous works have resulted in a better rationalization of the
      prescription (date of treatment initiation, interest of combined androgenic
      deprivation, ...) but uncertainties remain, such as the therapeutic interest of
      intermittent treatment, or of earlier hormone therapy combined with the treatment
      of the primitive tumour (adjuvant hormone therapy). Finally, at the time of the
      hormonal escape of which the molecular mechanisms remain unclear, no therapy has
      proven any efficacy in survival lengthening, and the treatment remains palliative
      and symptomatic. Although improved knowledge of prostate cancer aetiology is
      expected for a real disease prevention, early diagnosis at a curable stage of the
      disease (by PSA assessment) remains the only means for mortality reduction.

PMID- 15570707
TI  - Mineral radioactivity in sands as a mechanism for fixation of organic carbon on
      the early Earth.
AB  - Irradiation of organic molecules by mineral radioactivity is a feasible
      alternative to cosmic irradiation to precipitate solid organic carbon-rich matter
      on the early Earth. Radioactive (uranium- and thorium-rich) minerals have been
      concentrated at the Earth's surface, and accumulated accretionary coatings of
      carbon due to irradiation, since early Archean times. The organic accretion
      process could have occurred at the surface or in the sub-surface, and is
      independent of a terrestrial or extraterrestrial source for the carbon.

PMID- 15570708
TI  - Montmorillonite, oligonucleotides, RNA and origin of life.
AB  - Na-montmorillonite prepared from Volclay by the titration method facilitates the
      self-condensation of ImpA, the 5'-phosphorimidazolide derivative of adenosine. As
      was shown by AE-HPLC analysis and selective enzymatic hydrolysis of products,
      oligo(A)s formed in this reaction are 10 monomer units long and contain 67% 3',5'
      phosphodiester bonds (Ferris and Ertem, 1992a). Under the same reaction
      conditions, 5'-phosphorimidazolide derivatives of cytidine, uridine and guanosine
      also undergo self-condensation producing oligomers containing up to 12-14 monomer
      units for oligo(C)s to 6 monomer units for oligo(G)s. In oligo(C)s and oligo(U)s,
      75-80% of the monomers are linked by 2',5'-phosphodiester bonds. Hexamer and
      higher oligomers isolated from synthetic oligo(C)s formed by montmorillonite
      catalysis, which contain both 3',5'- and 2',5'-linkages, serve as catalysts for
      the non-enzymatic template directed synthesis of oligo(G)s from activated monomer
      2-MeImpG, guanosine 5'-phospho-2-methylimidazolide (Ertem and Ferris, 1996).
      Pentamer and higher oligomers containing exclusively 2',5'-linkages, which were
      isolated from the synthetic oligo(C)s, also serve as templates and produce
      oligo(G)s with both 2',5'- and 3',5'-phosphodiester bonds. Kinetic studies on
      montmorillonite catalyzed elongation rates of oligomers using the computer
      program SIMFIT demonstrated that the rate constants for the formation of
      oligo(A)s increased in the order of 2-mer < 3-mer < 4-mer ... < 7-mer (Kawamura
      and Ferris, 1994). A decameric primer, dA(pdA)8pA bound to montmorillonite was
      elongated to contain up to 50 monomer units by daily addition of activated
      monomer ImpA to the reaction mixture (Ferris, Hill and Orgel, 1996). Analysis of
      dimer fractions formed in the montmorillonite catalyzed reaction of binary and
      quaternary mixtures of ImpA, ImpC, 2-MeImpG and ImpU suggested that only a
      limited number of oligomers could have formed on the primitive Earth rather than
      equal amounts of all possible isomers (Ertem and Ferris, 2000). Formation of
      phosphodiester bonds between mononucleotides by montmorillonite catalysis is a
      fascinating discovery, and a significant step forward in efforts to find out how
      the first RNA-like oligomers might have formed in the course of chemical
      evolution. However, as has been pointed out in several publications, these
      systems should be regarded as models rather than a literal representation of
      prebiotic chemistry (Orgel, 1998; Joyce and Orgel, 1999; Schwartz, 1999).

PMID- 15570709
TI  - Why were polysaccharides necessary?
AB  - The main idea of this paper is that the primordial soup may be modelled by food
      systems whose structure-property relationship is based on non-specific
      interactions between denatured biopolymers. According to the proposed hypothesis,
      polysaccharides were the first biopolymers that decreased concentration of salts
      in the primordial soup, 'compatibilised' and drove the joint evolution of proto
      biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium
      could have resulted in phase separation of the primordial soup and concentration
      of the polypeptides and nucleic acids in the dispersed phase particles. The
      concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid
      supermacromolecules of conjugates. The cross-linking of proto-biopolymers could
      occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous
      mixed biopolymer dispersions and/or by covalent bonds due to the Maillard
      reaction. Cross-linking could have increased the local concentration of
      chemically different proto-biopolymers, fixed their relative positions and made
      their interactions reproducible. Attractive-repulsive interactions between cross
      linked proto-biopolymer chains could develop pairing of the monomer units,
      improved chemical stability (against hydrolysis) and led to their mutual
      catalytic activity and coding. Conjugates could probably evolve to the first self
      reproduced entities and then to specialized cellular organelles. Phase separation
      of the primordial soup with concentration of conjugates in the dispersed
      particles has probably resulted in proto-cells.

PMID- 15570710
TI  - Phenomenon of life: between equilibrium and non-linearity.
AB  - A model of ordering applicable to biological evolution is presented. It is shown
      that a steady state (more precisely approaching to a steady state) system of
      irreversible processes, under conditions of disproportionation of entropy,
      produces a lower-entropy product, that is, ordering. The ordering is defined as
      restricting of degrees of freedom: freedom of motion, interactions etc. The model
      differs from previous ones in that it relates the ordering to processes running
      not far from equilibrium, described in the linear field of non-equilibrium
      thermodynamics. It is shown that a system, which includes adenosine triphosphate
      (ATP) to adenosine diphosphate (ADP) conversion meets the demands of the physical
      model: it provides energy maintaining steady state conditions, and hydrolysis of
      ATP proceeding with consumption of water can be tightly conjugated with the most
      important reactions of synthesis of organic polymers (peptides, nucleotide chains
      etc.), which proceed with release of water. For these and other reasons ATP seems
      to be a key molecule of prebiotic evolution. It is argued that the elementary
      chemical reaction proceeding under control of an enzyme is not necessarily far
      from equilibrium. The experimental evidence supporting this idea, is presented.
      It is based on isotope data. Carbon isotope distribution in biochemical systems
      reveals regularity, which is inherent to steady state systems of chemical
      reactions, proceeding not far from equilibrium. In living organisms this feature
      appears at the statistical level, as many completely irreversible and non-linear
      processes occur in organisms. However not-far-from-equilibrium reactions are
      inherent to biochemical systems as a matter of principle. They are reconcilable
      with biochemical behavior. Extant organisms are highly evolved entities which,
      however, show in their basis the same features, as the simplest chemical systems
      must have had been involved in the origin of life. Some consequences following
      from the model, which may be significant for understanding the origin of life and
      the mechanism of biological evolution, are pointed out.

PMID- 15570711
TI  - Growth of methanogens on a Mars soil simulant.
AB  - Currently, the surface of Mars is probably too cold, too dry, and too oxidizing
      for life, as we know it, to exist. But the subsurface is another matter. Life
      forms that might exist below the surface could not obtain their energy from
      photosynthesis, but rather they would have to utilize chemical energy.
      Methanogens are one type of microorganism that might be able to survive below the
      surface of Mars. A potential habitat for existence of methanogens on Mars might
      be a geothermal source of hydrogen, possibly due to volcanic or hydrothermal
      activity, or the reaction of basalt and anaerobic water, carbon dioxide, which is
      abundant in the martian atmosphere, and of course, subsurface liquid water. We
      report here that certain methanogens can grow on a Mars soil simulant when
      supplied with carbon dioxide, molecular hydrogen, and varying amounts of water.

PMID- 15570712
TI  - How Hawaii/Pacific Basin Area Health Education Center (AHEC) is using technology
      to make the Pacific smaller.
AB  - INTRODUCTION: In order to improve health literacy in rural areas, the
      Hawaii/Pacific Basin AHEC and Ke 'Anuenue AHEC are working to connect rural
      communities via video teleconferencing. METHODS: Video teleconferencing
      connectivity has been established to 15 rural and underserved locations across
      Hawaii and to the Republic of the Marshall Islands. RESULTS: An average of 15
      individuals participate in weekly facilitated health education sessions.
      DISCUSSION: Participants have reported lifestyle change as a result of sessions
      and attendance is significantly increasing. In some areas, mid level health care
      professionals attend in order to obtain information for their patients.

PMID- 15570713
TI  - Distance learning on the Internet: web-based archived curriculum.
AB  - Web-based education through archived educational modules offers a significant
      opportunity to provide didactic education. By archiving lectures and teaching
      materials, it reduces the educators' time of preparation, especially when many
      students will need to take the same curriculum over a long period of time. The
      site can package educational material in multiple formats including audio, video,
      and readable text, allowing the student to tailor the educational experience to
      his/her learning preferences. This can be a stand-alone program, or integrated
      into a program combining distance and in-person education. Assessment through on
      line tests can also be conducted, but these must be considered open-book
      assessments where collaboration cannot be prevented. As such, this vehicle can be
      utilized effectively for continuing education programs in health care, where open
      book is permitted and credits are generally awarded on the honor system. However,
      tests for certificate courses should only be given with a proctor in attendance.
      In this instance, on-line tests can be used as pre-tests for the student, while
      being structured to enhance further learning.

PMID- 15570714
TI  - The virtual hospital: treating acute infections in the home by telemedicine.
AB  - The growth and aging of the population of Hawaii mandates a need for more
      effective utilization of hospital beds. One approach is early hospital discharge
      and outpatient treatment. However, as the acuity of illness increases,
      satisfactory outcomes of outpatient treatment maybe difficult to achieve. We have
      utilized telemedicine to closely monitor acutely ill patients with infections,
      such as community-acquired pneumonia, skin and soft tissue infections, and
      urinary tract infection, in the home setting. Our treatment paradigm achieved
      satisfactory outcomes, cost savings, and at the same time resulted in more rapid
      convalescence than hospitalization.

PMID- 15570715
TI  - An international landmine telehealth symposium between Hawaii and Thailand using
      an Internet2 and multi-protocol videoconferencing bridge.
AB  - An international telehealth symposium was conducted between healthcare
      institutions in Hawaii and Thailand using a combination of Asynchronous Transfer
      Mode, and Internet2 connectivity. Military and civilian experts exchanged
      information on the acute and rehabilitative care of landmine victims in Southeast
      Asia. Videoconferencing can promote civil-military cooperation in healthcare
      fields that have multiple international stakeholders.

PMID- 15570716
TI  - Shriners Hospitals for Children, Honolulu's experience with telemedicine: program
      implementation, maintenance, growth, and lessons learned.
AB  - Shriners Hospitals for Children, Honolulu Telemedicine Program conducts real-time
      video consultations with remotes sites in Hawaii, Guam, Saipan, American Samoa,
      the Federated States of Micronesia, and the Republic of the Marshall Islands. The
      program began in 1999 and has provided over 240 consultations. This report is a
      summary of the Shriners Hospitals experience and lessons learned regarding
      program implementation and maintenance.

PMID- 15570717
TI  - Augmentation of special-needs services and information to students and teachers
      "ASSIST"--a telehealth innovation providing school-based medical interventions.
AB  - An innovative school-based telehealth technology was introduced in Hawaii with
      the purposes of: (1) evaluating students for medical/developmental conditions
      with educational implications, (2) providing a professionally-monitored Internet
      based system of learning/development, and (3) delivering medically-based physical
      and occupational therapy at the students school. Electronically recorded
      satisfaction surveys from parents, teachers, and providers revealed significant
      improvement in all three areas.

PMID- 15570718
TI  - A novel approach to tele-echocardiography across the Pacific.
AB  - Telecardiology provides remote delayed interpretation of echocardiographic images
      through a store and forward program between the interpreting center, Tripler Army
      Medical Center, Honolulu Hawaii, and the image acquisition center, Guam Naval
      Hospital, Guam USA. This routine store and forward system has inherent delay,
      limiting application for management of acute medical conditions. In this case
      report we describe a novel methodology for real-time echocardiograpic
      interpretation methodology integrated methodology with the eICU system (VISICU
      Inc., Baltimore MD). This case report demonstrates the feasibility of a
      clinically relevant remote real-time echocardiographic interpretation strategy,
      utilizing commonly available equipment.

PMID- 15570719
TI  - Multi-tasking in medical professions at the 148th Annual Meeting of The Hawaii
      Medical Aassociation--September 3, 4, 5, 2004, Sheraton Waikiki, Honolulu.

PMID- 15570720
TI  - Integrating ecohealth in the school of medicine.

PMID- 15570721
TI  - In search of novel molecular targets in cancer: the diacyglycerol pathways.

PMID- 15570722
TI  - If you want something done right, do it yourself.

PMID- 15570723
TI  - Getting started in the electronic records game.

PMID- 15570724
TI  - Uncertainty clouds online, real-time world.

PMID- 15570725
TI  - I.T. helps battle 'the big C'.

PMID- 15570726
TI  - Mobile leadership from a group practice.

PMID- 15570727
TI  - Getting generosity to pay off.

PMID- 15570728
TI  - Ease on down the mobile road.

PMID- 15570730
TI  - Provider promulgates patients' progress.

PMID- 15570729
TI  - Comply with HIPAA fast, get it right.

PMID- 15570731
TI  - Readers perspectives. HIMSS Conference and Exhibition is well worth the time and
      expense to attend?

PMID- 15570732
TI  - Can we learn anything from the tragedy that is the Schiavo Case?

PMID- 15570733
TI  - The Vioxx withdrawal: latest in the COX-2 controversies.

PMID- 15570734
TI  - A world without Vioxx: to COX-2 or not to COX-2?

PMID- 15570735
TI  - Benign prostatic hyperplasia: now we can begin to tailor treatment.
AB  - Our treatment strategies for benign prostatic hyperplasia (BPH) have changed,
      with new insights into the pathophysiology of the disease, new clinical trials,
      and surgical advances. We present an update on treatment options and a diagnostic
      and treatment algorithm for this condition.

PMID- 15570736
TI  - Understanding valvular heart disease in patients with systemic autoimmune
      diseases.
AB  - Specific systemic autoimmune diseases are associated with distict valvular heart
      disorders. We discuss the valvular disorders associated with rheumatoid
      arthritis, systemic lupus erythematosus, antiphospholipid antibody syndrome, the
      seronegative spondyloarthropathies, the systemic vasculitides, and scleroderma.

PMID- 15570737
TI  - Radiologic imaging in rhinosinusitis.
AB  - To diagnose rhinosinusitis, the history and physical examination usually suffice.
      However, imaging may be necessary to guide further treatment in patients whose
      condition is refractory to treatment and patients with chronic or recurrent acute
      rhinosinusitis or acute rhinosinusitis with complications. A brief review of
      current imaging options and their recommended use is presented.

PMID- 15570738
TI  - A practical program for preventing delirium in hospitalized elderly patients.
AB  - Delirium in hospitalized elderly patients is common and often unrecognized
      (especially the hypoactive type), and can lead to serious complications. A
      systematic program can improve the rate of recognition of this problem and
      decrease its incidence, and is cost-effective.

PMID- 15570739
TI  - Safe use of opioids in chronic noncancer pain.
AB  - Many physicians avoid prescribing opioid analgesics for chronic pain because of
      misconceptions or fears about efficacy, adverse effects, abuse, and addiction
      potential. We discuss these issues and offer suggestions for the rational use of
      opioid analgesics in patients with chronic noncancer pain.

PMID- 15570740
TI  - A guide to informed consent for clinician-investigators.
AB  - Informed consent in clinical research is a matter of both ethics and federal
      regulation. A research subject must enter a study voluntarily, be informed about
      risks and benefits, and understand the difference between experiment and
      treatment.

PMID- 15570741
TI  - Growth performance, carcass characteristics and bioavailability of isoflavones in
      pigs fed soy bean based diets.
AB  - A growth trial with 38 weaners (castrated male pigs) was designed to compare the
      growth performance and carcass quality of pigs fed diets containing either soy
      bean meal or soy protein concentrate in a pair-feeding design. Soy bean meal
      (SBM) and soy protein concentrate (SPC) differed in isoflavone (daidzein plus
      genistein) content (782 microg/g in SBM and 125 microg/g in SPC, respectively).
      During the experiment, all pigs were fed four-phases-diets characterized by
      decreasing protein concentrations with increasing age (weaner I, weaner II,
      grower, finisher diets). Rations of control and experimental groups were
      isoenergetic, isonitrogenous, and isoaminogen. The weanling pigs with an initial
      live weight of 8.4 +/- 1.1 kg were allotted to flat deck boxes. During the
      growing/finishing period (days 70-170 of age), the pigs were housed in single
      boxes. Both, the weaning and the grower/finishing performances (daily body weight
      gain, feed intake, feed conversion ratio) were similar in both groups. No
      differences were found between the groups in carcass composition (percentages of
      cuts, tissues, and protein/fat), and meat quality of pigs. Moreover, the IGF-1R
      mRNA expression in longissimus muscle was not influenced by the kind of soy
      product. However, circulating levels of isoflavones were clearly different
      between pigs fed SBM (genistein 239 +/- 44; daidzein 162 +/- 42; equol 12 +/- 4
      ng/ml plasma) and animals fed SPC (genistein 22 +/- 9 and daidzein 8 +/- 3, and
      equol 10 +/- 3 ng/ml plasma). The results confirm the expected differences in the
      bioavailability of soy isoflavones, yet, there were no significant differences in
      performance of pigs fed either soy bean meal or soy protein concentrate.

PMID- 15570742
TI  - Effects of conjugated linoleic acid levels and feeding intervals on performance,
      carcass traits and fatty acid composition of finishing barrows.
AB  - Two experiments were conducted to investigate the effects of dietary conjugated
      linoleic acid (CLA) on performance, carcass traits, fatty acid composition and
      subcutaneous adipose tissue cellularity in finishing barrows. In Experiment 1, 54
      crossbred barrows were allotted to one of three treatments, with six pens per
      treatment and three barrows in each pen. The pigs were fed a diet containing 0,
      2, or 4% CLA oil for 6 weeks. Daily gain (P < 0.01) and feed efficiency (P <
      0.01) improved with dietary CLA. Loin muscle area (P = 0.01) and intramuscular
      fat (P = 0.01) increased while 10th rib fat (P = 0.03) and last rib fat (P =
      0.02) thickness decreased with increasing dietary CLA. Total CLA isomers
      increased (P < 0.01) with increasing dietary CLA. Myristic, palmitic and stearic
      acid levels were increased while oleic, linoleic, linolenic and arachidonic acid
      decreased in loin muscle and subcutaneous adipose tissue. In Experiment 2,
      barrows (n = 54) were allotted to one of two treatments with nine pens per
      treatment and three pigs in each pen. Pigs were fed a diet supplemented with 4%
      CLA for 3 or 6 weeks before slaughter. Over the entire experimental period, daily
      gain and feed efficiency were higher (P < 0.01) when CLA was fed for a longer
      period. Loin muscle area (P < 0.01) and intramuscular fat (P < 0.01) increased
      while backfat thickness at the 10th (P = 0.03) and last rib (P = 0.04) decreased
      when CLA was fed for 6 vs. 3 weeks. The number of cells in subcutaneous adipose
      tissue was not affected while adipocyte volume decreased (P = 0.01) with longer
      feeding time on dietary CLA. The increased CLA content of pork from CLA fed pigs
      provides the pork industry with an opportunity to provide value-added, healthful
      meat products for human consumption with respect to CLA intake and potential
      improvements in human health.

PMID- 15570743
TI  - Use of the mobile nylon bag technique to determine the digestible energy content
      of traditional and non-traditional feeds for swine.
AB  - The following experiment was conducted using the mobile nylon bag technique
      (MNBT) to determine dry matter and energy digestibility in traditional feeds as
      well as non-traditional feeds in order to calculate digestible energy (DE) values
      for use in ration formulation programmes. A total of 22 ingredients were tested
      in this experiment including the traditional cereal grains barley, corn, oats and
      wheat, as well as secondary cereal grains such as normal and low viscosity rye,
      low lignin and high fat oat groats, wheat heavies and # 1 wheat screenings and a
      new bread wheat designated as CDC Teal. Three legumes (lupines, peas and
      dehydrated alfalfa), three varieties of canary seed (CDC Maria, dehulled CDC
      Maria and Keet), and raw and micronized canola seed were tested as protein
      sources. Finally, three oilseed meals obtained from the Chinese feed industry
      (Chinese rapeseed meal, Chinese cottonseed meal and extruded full-fat soybean
      meal) were also included. After simulating gastric digestion the nylon bags were
      inserted into the duodenum of five barrows through simple duodenal T-cannulae.
      Eight bags were administered to each pig daily. Ten nylon bags were prepared for
      each feed with two bags being inserted into each of the five barrows. A total of
      220 bags were inserted over a 7-day period. The overall results of this
      experiment indicate that the MNBT has great potential for use in determining the
      digestible energy content of swine feeds. For the most part, values obtained in
      the present experiment compared favourably with previously published values. Four
      feedstuffs produced digestible energy values that differed by greater than 5%
      from previously reported values. However, variation in chemical content provided
      a reasonable explanation for these discrepancies. The MNBT has several advantages
      compared with conventional digestibility methods in that many feeds can be tested
      in a relatively short duration of time with significantly fewer animals being
      used, only small amounts of feed are required and the test allows for energy
      measurements in feedstuffs that would not normally be fed to pigs as a single
      ingredient. Additional research on a wider variety of feedstuffs should be
      conducted to confirm the potential of the MNBT as a tool to accurately determine
      DE values for swine.

PMID- 15570744
TI  - Nutritional assessment and fate of DNA of soybean meal from roundup ready or
      conventional soybeans using rats.
AB  - This study was conducted to compare the safety of soybean meal prepared from
      genetically modified (GM) glyphosate-tolerant (Roundup Ready; RR) soybeans and
      conventional soybeans. Eighty Sprague-Dawley rats (40 males and 40 females) were
      randomly allotted to one of four groups according to sex and body weight for a 13
      week feeding experiment. The rats were fed corn-based diets containing 60%
      conventional soybean meal, a mixture of 30% conventional and 30% RR soybean meal,
      60% or 90% RR soybean meal. All diets were adjusted to an identical nutrient
      level except the 90% RR diet. The two soybean meals were similar in chemical
      analysis and amino acid composition. During the 13-week growth trial, body weight
      (P < 0.05) and feed intake (P < 0.05) decreased only in rats fed with 90% RR
      soybean meal at the first week. No treatment-related deaths occurred during the
      experiment. Gross necropsy findings, haematological or urinalysis values and
      clinical serum parameters showed no meaningful differences between rats fed the
      control and RR soybean meals. A 145 bp of cp4 epsps gene specific for the GM
      constructs from RR soybean meal or a 407 bp of lec gene from endogenous soybean
      DNA could not be detected in investigated masseter muscle samples. No adverse
      effects of glyphosate-tolerant soybean meal on rats were seen even at levels as
      high as 90% of the diet.

PMID- 15570745
TI  - In vitro studies on the evaluation of mycotoxin detoxifying agents for their
      efficacy on deoxynivalenol and zearalenone.
AB  - A simple in vitro system was developed to study the efficacy of commercially
      available mycotoxin detoxifying agents and adsorbing substances as feed additives
      to detoxify deoxynivalenol (DON) and zearalenone (ZON) in situ. The in vitro
      model simulates the conditions (pH, temperature and transit time) of the porcine
      gastrointestinal tract, as pigs react most sensitively to these mycotoxins. The
      commercially available products were not effective in detoxifying DON and ZON
      under the applied conditions, while activated carbon was able to bind both toxins
      and cholestyramine, and a modified aluminosilicate showed good adsorption
      abilities for ZON. Data obtained in dose dependency studies showed an estimated
      adsorption capacity of cholestyramine and the modified aluminosilicate of 11.7
      and 5.7 g ZON/kg detoxifying agent. The in vitro system deployed in the present
      study was demonstrated to be a simple, helpful tool in screening substances for
      their ability to detoxify DON and ZON under the simulated conditions of the
      porcine gastrointestinal tract. Nonetheless in vivo experiments are indispensable
      to proof the efficacy.

PMID- 15570746
TI  - Digesta characteristics of dorsal, middle and ventral rumen of cows fed with
      different hay qualities and concentrate levels.
AB  - The influence of fibre content of hay (H) and concentrate level (C) on local
      differences in the composition of ruminal digesta (ratio of solid to fluid
      digesta, DM, NDF, ADF and ADL content), particle size (MPL), specific gravity
      (SG) and fermentation (pH and concentrations of SCFA and bicarbonate) have been
      tested on two ruminally cannulated Friesian cows (520 kg BW) which were fed
      restricted, using individual cows as experimental units. Digesta samples were
      collected via cannula from three rumen layers: 5 to 10 cm (top) and 25-35 cm
      beneath the top of the particle mat (middle) and 5-10 cm above the rumen floor
      (bottom). For a main plot treatment (H x C), repeated samples were collected at
      four time intervals (1 h before and 2, 5 and 10 h after morning feeding) on each
      of two days. From top to bottom rumen the share of solid digesta mass (SM), DM
      and NDF contents of squeezed digesta fluid (SRF) and concentration of SCFA
      decreased (P < 0.05); pH and bicarbonate concentration increased (P < 0.05),
      while DM, NDF, ADF and ADL contents in SM, MPL and SG did not differ. Higher NDF
      content of hay (from 47-62%) increased SM, fibre fractions in SM, MPL, pH and
      concentration of bicarbonate in ruminal digesta, especially when 50% concentrate
      was given, while SG decreased. When the concentrate level was enhanced from 20 to
      50%, digesta SM, MPL and the content of DM and NDF in SRF increased, while pH,
      concentrations of SCFA and acetate decreased when low-fibre hay was given. With
      longer time after feeding the digesta SM was reduced and fibre content in SM
      increased. The increase of the fibre content of hay reduced the possible negative
      effect of high concentrate level on the stratification of ruminal digesta. The
      decrease of the fibre content of hay promised better conditions for fibre
      digestion in the rumen when concentrate availability is limited.

PMID- 15570747
TI  - Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (II).
AB  - The precise cause(s) of Crohn's disease and ulcerative colitis are unknown. From
      animal models and human studies it is well established that gut bacterial flora
      are essential for inducing the bowel inflammation. Animal models, when kept in a
      germ-free environment, do not develop colitis until the gut flora is
      reconstituted. It is not clear whether the bacterial antigens (Ags) from the
      normal flora or some other pathogenic bacterial Ags induce/propagate the
      inflammatory process in inflammatory bowel disease (IBD). Despite extensive
      research it has not been possible to identify any specific bacteria or virus as a
      credible cause of IBD. Recent understanding of quorum sensing molecules (QSMs)
      secreted by bacteria helps to explain the community behaviour in bacterial
      species. When QSMs reach a defined concentration, they activate bacterial
      proliferation and a number of virulence genes. Also, these molecules have been
      found to modulate the immune system to the advantage of the gut bacteria. They
      have not been well studied, however, in the gut. Inappropriate secretion of QSMs
      may alter the gut-associated lymphoid tissue (GALT) and, thereby, deregulate the
      immune tolerance normally present. Usefulness of probiotics and their immune
      modulating effects are being increasingly reported. Probiotics are also being
      used in the treatment of IBD. The interaction between the epithelial cells and
      the gut flora is very important as this is the first line of contact; this
      interaction may determine the induction of tolerance and mucosal integrity or
      immune activity, tissue inflammation and abnormal permeability. The latter is
      documented in patients with IBD and their healthy relatives. This may be an
      important factor in disruption of mucosal integrity and GALT dysfunction.

PMID- 15570748
TI  - Molecular strategies and 111in-labelled somatostatin analogues in defining the
      management of neuroendocrine tumour disease: a new paradigm for surgical
      management.
AB  - This manuscript provides a gene-chip examination of gastric ECL cell
      proliferation in an animal model of neuroendocrine tumour disease. Data that were
      used to identify molecular targets were then utilised to develop novel
      therapeutic strategies as appropriate adjuncts to surgery in human disease.
      Alterations in growth-mediated cell signaling (the AP-1 pathway) and in the cell
      cycle were identified in ECL cell tumours in the animal model and confirmed in
      human tumour tissue. The growth-inhibitory somatostatin receptor subtype 2 was
      identified as a potential clinical target. An investigation of patients with
      neuroendocrine tumours treated using SSTR2 targeted radiotherapy
      [111In]pentetreotide producing encouraging preliminary results. Fifty-six per
      cent of patients with evaluable hormone markers demonstrated stable levels or a
      significant decrease in one or more measured markers. This data demonstrate that
      gene pathways recognised to be altered in an animal model of a human disease can
      be used to identify therapeutic agents. This approach was successfully used to
      discover novel strategies that can be both effective and appropriate adjuncts to
      surgery for patients with neuroendocrine tumour disease.

PMID- 15570749
TI  - Utility of the lithoclast in the treatment of upper, middle and lower ureteric
      calculi.
AB  - OBJECTIVE: The aim of this study was to evaluate the utility and efficacy of
      lithoclast in the treatment of upper, middle and lower ureteric calculi. PATIENTS
      AND METHODS: Over a period of 6 1/2 years, we have treated 529 ureteric stones
      which failed to pass spontaneously within a 2-week period. Patients were
      evaluated for number, site, size and laterality of stones. Patients with
      ureteroscopy failure were excluded from the study. Once the stone(s) was (were)
      localised with the ureteroscope, it (they) was (were) treated with the Swiss
      lithoclast. RESULTS: Complete fragmentation was achieved in 99% of cases with
      lower, 97% with mid and 71% with upper ureteric calculi, respectively. The
      lithotripsy time was only 8.6 minutes for stones < or =1 cm and 14.8 minutes for
      stones ranging from 1.1 to 2.0 cm. Completely fragmented stones cleared
      spontaneously within two weeks in 98% of cases and all patients were free of
      calculi one month after the procedure. Retreatment with the lithoclast was
      required in six patients for large residual fragments. The mean hospital stay was
      1.2 days. Complications were encountered in 6.8% of cases and were managed
      conservatively. CONCLUSIONS: Pneumatic lithotripsy is an excellent form of
      treatment for lower and mid-ureteric calculi. It is a very reliable, highly
      effective, rapid and safe procedure.

PMID- 15570750
TI  - A simple technique for the retention of a subcuticular suture.
AB  - The retention of a subcuticular stitch using absorbable suture has been performed
      using a variety of methods. These techniques may be difficult to master by
      surgeons new to the skill and have been associated with problems such as "dog
      ears" and a bulky knot that becomes difficult to bury. The latter can also be
      responsible for wound gapping especially of small wounds. The procedure described
      here provides a secure mechanism for retaining the subcuticular suture with
      minimal bulk to the knot. It is easy to master, does not produce wound gaping and
      is suitable for all wound sizes.

PMID- 15570751
TI  - Surveillance for Barrett's oesophagus: is there light the end of the metaplastic
      tunnel?
AB  - Metaplastic change of the oesophageal epithelium from normal stratified squamous
      to columnar-lined with intestinal metaplasia results in an increased risk of
      development of adenocarcinoma. As a result, endoscopic surveillance has been
      recommended for the surgically-fit patient. The evidence that these programmes
      are altering clinical outcome to any major degree, however, is weak. This review
      highlights some of the areas of controversy and outstanding points that need to
      be clarified to allow establishment of evidence-based medicine for this
      condition.

PMID- 15570752
TI  - Revalidation--are we fixing a system that wasn't broken?
AB  - In 10 years, the medical profession in the U.K. has moved from a loose system of
      self regulation, through reluctant and patchy compliance with recorded continuing
      medical education (CME) to statutory obligations for 5-yearly revalidation which
      will control the issuing of a licence to practise for all doctors. The profession
      initially viewed these changes with dismissive cynicism, but the new rules are
      now being viewed with trepidation and paranoia. Royal Colleges can still play a
      central role in the development of the Revalidation process and must work
      together to develop appraisal as a meaningful tool to be used for the benefit of
      patient and doctor.

PMID- 15570753
TI  - Horseshoe kidney transplantation.
AB  - Even though the number of patients awaiting renal transplant is rapidly
      increasing, the donor pool remains relatively stable. In an attempt to increase
      this pool, marginal kidneys and kidneys with congenital anatomical variations are
      being used. Horseshoe kidneys, being the most common renal fusion anomaly, can
      provide a useful solution to the ever-increasing gap between demand and supply.
      These kidneys have been successfully transplanted en bloc into a single recipient
      or, alternatively they have been divided and transplanted into 2 recipients. We
      report a case of the successful transplantation of an en bloc horseshoe kidney
      into a single recipient. To the best of our knowledge this is the first of its
      kind in the U.K. The relevant literature is also reviewed with the aim of raising
      awareness about the necessity and promising outcomes of such transplants.

PMID- 15570754
TI  - Aneurysm of the inferior vena cava.
AB  - Aneurysms of the inferior vena cava (IVC) are extremely rare, with a range of
      reported presentations including deep venous thrombosis. Computerised Tomography
      (CT) and Magnetic Resonance Imaging (MRI) scans are suggested appropriate
      diagnostic imaging modalities, but even then it may not be possible to
      differentiate between an IVC aneurysm and a retroperitoneal tumour. This case
      illustrates that an IVC aneurysm should be considered in the differential
      diagnosis of a retroperitoneal tumour.

PMID- 15570755
TI  - Early twentieth century surgical urology: the 1909-1939 experience of Henry Wade.
AB  - This historical review uses the experience of Henry Wade (1876-1955) to examine
      the state of surgical urology in the early decades of the twentieth century. For
      50 years, Wade was a central figure in the life of the Royal College of Surgeons
      of Edinburgh. His work epitomises Scottish surgery in the years between 1909 and
      1939. Wade adopted every available technique to arrive at the precise diagnosis
      of urinary tract disease. An exact clinical history and examination were followed
      by the testing of the urine, the analysis of the blood, radiography and
      cystoscopy. During his time, urological surgery was revolutionised by the advent
      of excretion pyelography. Soon afterwards, blood transfusion and the first
      antibacterial agents began to transform prognosis. Nevertheless, the urological
      scene was still dominated by the hazards of prostatectomy, the high frequency of
      renal tuberculosis, and the challenges of bladder and renal cancer. The virtual
      impossibility of eradicating malignant prostatic tumours, much less common in a
      population where the mean expectation of life for males was 20 to 30 years less
      than now, relegated this insidious disorder to a small place in his practice. In
      30 years of active consultant life, Wade brought to surgical urology the skills,
      integrity, knowledge and determination that had already led him to prominence in
      the fields of cancer research and in orthopaedic and military surgery.

PMID- 15570756
TI  - Surgical informatics on the Internet: any improvement?
AB  - PURPOSE: The Internet is a popular, but ungoverned, source of medical
      information. This study tracked the change in performance of commonly available
      search engines and the quality of medical data therein over a four-year period.
      METHODS: We compared the accuracy of information on a commonly performed surgical
      procedure (vasectomy) using six standard search engines in a four-year period and
      with two recently developed search engines. The top 25 ranked sites cited by each
      search engine were scored for description of the procedure, post-operative
      instructions, complications and unproven associations. RESULTS: There was no
      improvement in quality of individual sites over the study period. Additionally,
      the hit rate of search engines remained poor with 27 sites cited (40%) in 2002
      either irrelevant or unavailable. DISCUSSION: Few useful sites with accurate
      information on surgical procedures are available on the Internet and simple
      search strategies fail to identify site quality or relevancy. CONCLUSION: At
      present, the Internet cannot be recommended as a reliable resource for many
      aspects of health information for patients. The onus is on health-care providers
      to provide high quality sites and direct patients to these sources of reliable
      information

PMID- 15570757
TI  - "A simple method of mesorectal transection for carcinoma of upper third of
      rectum" by Y. Srinivas, A. Renwick, P. McArdle and A. MacDonald J R Coll Surg
      Edinb 2001; 46: 338-339.

PMID- 15570758
TI  - Re: "The role of elective colectomy for diverticular disease" by Somesakar et al
      J R Coll Edinb 2002; 47:2.

PMID- 15570759
TI  - Re: "Inguinal hernia repair" by I.M.C. MacIntyre J R Coll Surg Edinb 2001; 46:
      349-53.

PMID- 15570760
TI  - Re: "Swimmers view: a diagnostic adjunct for oesophageal foreign bodies" by
      Kanagalingam et al J R Coll Edinb 2002; 47: 4; 641-42.

PMID- 15570761
TI  - Re: "Clinical relevance of the delay in endoscopic diagnosis of gastric cancer"
      by Amin et al J R Coll Surg Edinb 2002; 47: 681-4.

PMID- 15570762
TI  - Re: "Percutaneous extra-articular excision of femoral neck osteoid osteoma: a
      report of a new method" by Chaarani et al J R Coll Surg Edinb 2002 Volume 47: 5;
      705-08.

PMID- 15570763
TI  - Surgical sepsis: dysregulation of immune function and therapeutic implications.
AB  - Sepsis is defined clinically as the systemic inflammatory response of the host to
      the documented systemic infection. The pathophysiological disturbance involves
      both the innate and adaptive immune systems encompassing cellular immunity,
      humoral components and the complement system. Dendritic cells (antigen-presenting
      cells) are key cells involved in the regulation of the immune response in sepsis,
      in particular in activating T cells and especially inducing the production and
      secretion of specific cytokines. These are the main mediators in establishing
      prominent disturbances of inflammation in patients with sepsis. The clinical
      features of the sepsis syndrome may vary from minor clinical disturbances to
      severe multiple organ failure and death of the host. Appropriate therapeutic
      strategies for patients with sepsis utilise conventional therapy and new novel
      forms of treatment, which are showing promise for the future.

PMID- 15570764
TI  - Dentistry and the medically compromised patient.
AB  - Certain medical conditions and their accompanying drug treatment do have an
      impact upon oral structures and the delivery of dental care. Recent evidence
      suggests that oral health could be a significant risk factor for coronary artery
      disease. Many medical conditions can affect dental care are often over-stated and
      lack an evidence base. Examples include the need for antibiotic cover in patients
      at risk from infective endocarditis and the necessity to provide supplementary
      corticosteroids for those patients on longterm steroid therapy. By contrast,
      certain systematic drug treatments can have a profound affect on the oral tissue.
      The most obvious is drug-induced gingival overgrowth. Drugs frequently implicated
      in this unwanted effect include phenytoin, ciclosporin and the calcium channel
      blockers. Several risk factors for drug-induced overgrowth have been identified
      and include age, sex, peridontal variables and a range of drug pharmacokinetic
      variables. The relationship between oral health and coronary artery disease opens
      up a potentially new vista for the delivery of oral care. Although the
      association is convincing, casualty has not been established. If casualty for
      this relationship can be confirmed then the delivery of dental care and the
      promotion of oral health will receive a significant impetus.

PMID- 15570765
TI  - Attributes of trainers for postgraduate training in general surgery--a national
      consensus.
AB  - BACKGROUND: The aim of this study was to obtain consensus amongst consultant
      surgeons on the attributes of a good surgical trainer that can be used to inform
      continuing professional development programmes for trainers. METHODS: good
      trainer attributes were generated from an intensive qualitative study using a
      participative inquiry process with consultant general surgeons and specialist
      registrars in the Tayside region. These good trainer attributes were then used as
      the basis of a modified Delphi study; the early rounds of the Delphi
      simultaneously sought participants' views concerning stated attributes and sought
      to generate new attributes. A final Delphi questionnaire was sent to all 180
      consultant general surgeons in Scotland to identify consensus. RESULTS: The first
      two rounds of the Delphi process produced 45 attributes covering seven themes:
      interest in training, trainer as a team member, communication, receptiveness to
      trainee needs, trainer as a role model, reflection on practice and clinical and
      operative competence. The final survey identified significant consensus among
      surgeons. Clinical and operative competence achieved the highest consensus with
      89.2% of surgeons believing it to be an essential attribute. CONCLUSIONS: The
      results indicate that there is consensus on the seven themes identified as
      essential for a trainer in general surgery. The recognition of the importance by
      trainers of non-surgical trainer attributes in the changed training structure is
      encouraging. Surgeons' level of awareness of their roles as a trainer will help
      inform the level and direction of trainer training and support required as part
      of a flexible and continuing developmental process.

PMID- 15570766
TI  - Predictors of gastrointestinal complications after conventional and beating heart
      coronary surgery.
AB  - BACKGROUND: Gastrointestinal complications after cardiac surgery remain a
      significant problem despite improvements in pre-operative, operative and post
      operative care. The pathophysiology is uncertain, and their prevention remains
      suboptimal. This prospective, randomised study was designed to define the role of
      cardiopulmonary bypass (CPB) and cardioplegic arrest in the pathogenesis of
      gastrointestinal complications following coronary artery surgery. METHODS AND
      RESULTS: Three hundred patients were prospectively randomised to (1) on-pump
      conventional coronary artery surgery [150 patients, 114 men, mean age 64 (45-75
      years)] with mild hypothermic (32c) CPB and cardioplegic arrest of the heart or
      (2) off-pump surgery [150 patients, 113 men, mean age 64 (38-66) years] on the
      beating heart. The association of perioperative factors with gastrointestinal
      complications was investigated by univariate analysis. Significant variables were
      then included into a stepwise logistic regression model to ascertain their
      independent influence on the occurrence of gastrointestinal complications. There
      were no significant baseline differences between the groups. Eleven patients in
      the on-pump group and one patient in the off-pump group had post-operative
      gastrointestinal complications. Univariate analysis showed that CPB inclusive of
      cardioplegic arrest, left ventricular ejection fraction <50%, emergency surgery,
      prolonged aortic cross clamp and CPB time, post-operative low cardiac output
      syndrome, post-operative inotropic requirement, new onset atrial fibrillation
      (AF), excessive post-operative blood loss and redo thoracotomy <24 hours were
      predictors of gastrointestinal complications after coronary artery surgery (all
      p<0.05). However, stepwise multivariate regression analysis identified CPB
      inclusive of cardioplegic arrest as the only predictor of post-operative
      gastrointestinal complications (OR7.4; CI 3.4-17.9). CONCLUSIONS: Cardiopulmonary
      bypass, inclusive of cardioplegic arrest, is the main independent predictor of
      post-operative gastrointestinal complications in patients undergoing coronary
      revascularisation.

PMID- 15570767
TI  - A comparative study of post-operative pain in laser epithelial keratomileusis
      versus photorefractive keratectomy.
AB  - BACKGROUND: To compare the level of post-operative pain associated with two
      methods of excimer laser corneal refractive surgery: PRK (photorefractive
      keratectomy) versus LASEK (laser epithelial keratomileusis). METHODS: 14 patients
      undergoing simultaneous bilateral myopic PRK were included in the study. The
      first eye of each patient was randomly allocated for treatment by either LASEK or
      PRK with alcohol-assisted epithelial debridement and second eyes were treated
      with the other technique. Laser corneal ablation was performed with Nidek EC-5000
      excimer laser by one surgeon (MAA) using the same algorithm. Post-operatively,
      all patients had declofenac sodium 0.1% eye drops four times a day, lorazepam 2mg
      at night and two solpadol (paracetamol 500mg and codeine phosphate 30mg) tablets
      every six hours orally for two days. Chloramphenicol 0.5% drops four times a day
      were also administered for seven days. The level of pain in each eye was assessed
      2, 12, 24 and 48 hours following laser surgery using a descriptive pain score
      from 0 to 10. Statistical analysis was performed using paired t test. RESULTS:
      The mean pain score at two hours post-operatively was 3.5 +/- 2.24(SD) in the
      LASEK group and 5.7 +/- 2.02(SD) in the PRK group. This difference is
      statistically significant. At 12 hours it was 4.33 +/- 2.53 (SD) and 4.75 +/-
      2.30 (SD), at 24 hours it was 3.71 +/-2.84 (SD) and 4.00 +/- 2.48 (SD), and at 48
      hours it was 2.86 +/- 3.43 (SD) and 2.21 +/- 2.55 (SD). There was no
      statistically significant difference in the pain score at these intervals.
      CONCLUSIONS: Post-operative pain was less in eyes treated with LASEK than eyes
      treated with PRK 2 hours following laser surgery. This was statisticaly
      significant and there was no statistically significant difference at 12, 24 and
      48 hours.

PMID- 15570768
TI  - A selective approach to histopathology of the gallbladder is justifiable.
AB  - BACKGROUND: Recent changes in the NHS have led to a considerably increased
      workload for histopathologists prompting the publication of guidelines from the
      Royal College of Pathologists regarding specimen analysis. In most hospitals,
      cholecystectomy specimens are routinely sent for histology regardless of whether
      or not there is any visible macroscopic abnormality suggestive of malignancy. Our
      aim was to assess whether it would be safe to adopt a policy of processing only
      suspicious gallbladders without compromising patient management and outcome.
      METHODS: A retrospective analysis of all cholecystectomies performed between 1995
      and 1999 was conducted using computerised histopathology records and patient
      notes. The histopathology department has a standardised procedure for the
      evaluation of cholecystectomy specimens and all gallbladders had been processed
      in this manner. RESULTS: 1308 patients had undergone cholecystectomy (mean
      262/year). All specimens had been sent for histology: 1249 of the specimens
      showed chronic cholecystitis, 38 acute cholecystitis or empyema and 16 were
      removed as part of another procedure. In five gallbladders there was evidence of
      primary carcinoma. In all cases the gallbladder was opened at the time of surgery
      (as commented upon in the operation notes) and all showed macroscopic evidence
      suggestive of carcinoma. Pre-operative ultrasound scanning identified probable
      carcinoma in three of the five cases. CONCLUSIONS: All cases of gallbladder
      carcinoma were diagnosed pre-operatively or intra-operatively and a histological
      diagnosis did not alter the management or outcome of any of these patients.
      Selective histopathology of the gallbladder is safe and may be a more measured
      approach saving histolopathology departments time and money.

PMID- 15570769
TI  - Isolated chylopericardium.
AB  - A 25-year-old male was discovered to have an asymptomatic pericardial effusion
      during routine pre-employment medical evaluation. During pericardiocentesis 1200
      ml of milky-white fluid was obtained; subsequent biochemical evaluation confirmed
      the chylous nature of this fluid. Following thorough evaluation a diagnosis of
      isolated chylopericardium was made. Following several recurrences he underwent
      thoracotomy with ligation of the thoracic duct and creation of a pericardial
      window. There are relatively few published reports of true isolated
      chylopericardium and the aetiology and pathogenesis remain unknown. A primary
      abnormality of the thoracic lymphatic valve system is postulated. The most
      effective treatment is surgical with ligation of the thoracic duct above the
      diaphragm and creation of a pericardial window

PMID- 15570770
TI  - Re: Al Mulla A, Purva M and Behbehani A. Fireworks injury: temporal bone
      penetration and a wooden intra-cranial foreign body. J R Coll Surg Edinb 2001; 46
      (4): 249-51.

PMID- 15570771
TI  - Re: Chan MYP, Tan C, Chiu MT, Ng YY. Alvarado score: an admission criterion in
      patients with right iliac fossa pain. Surg J R Coll Surg Edinb Irel 2003; 1 (1):
      39-41.

PMID- 15570772
TI  - Re: J.A. Harty, D. Brennan, S. Eustace, J. O'Byrne. Percutaneous cementoplasty of
      acetabular bony metastasis. Surg J R Coil Surg Edinb Irel 2003. 1 (1): 48-59.

PMID- 15570773
TI  - Re: H.A. Vohra. Laboratory research during training. Surg J R Coll Surg Edinb
      Irel 2003; 1 (1): 60-61.

PMID- 15570774
TI  - The evolution of extracranial carotid artery surgery as seen by one surgeon over
      the past 40 years.
AB  - Carotid endarterectomy is one of the most common vascular and neurosurgical
      operations. Controversies regarding its indications and safety have required
      several decades before general resolution, while its methodology is still
      debated. The first operations are described with particular emphasis on the epic
      successful procedure in 1954 by Eastcott and Rob. Early procedures were on
      patients with frank strokes with poor results. The development of carotid
      endarterectomy was slow because neurologists were unsure of its effectiveness and
      safety as the mortality and stroke results recorded by untrained surgeons were
      unacceptable. It was not until some 35 years after its introduction that
      randomised controlled trials, both in North America and Europe, defined its
      indications and demonstrated its benefits for both symptomatic and asymptomatic
      carotid stenosis. Clamping of the carotid vessels, required during
      endarterectomy, may result in various degrees of cerebral ischaemia. Methods to
      determine which patients need shunting are compared. The author has employed
      local neck block anesthesia since 1972, which is the only method that provides
      constant neurological assessment for selective shunting during carotid cross
      clamping. Evidence is presented showing that local anaesthesia also reduces
      complications of general anaesthesia, especially myocardial infarction. The
      technique of neck block, conventional endarterectomy and two varieties of
      eversion endarterectomy for carotid disease are described. Each of these
      techniques of endarterectomy is advantageous in certain circumstances, suggesting
      that vascular surgeons should ideally be proficient in each. Likewise, the
      management of early stroke after operation, stenotic or occluded external carotid
      the presence of retinal Hollenhorst plaques, and the totally occluded internal
      carotid, is presented. Finally, observations on some famous figures who suffered
      from cerebrovascular complications secondary to carotid disease and what effect
      it may have had on world history is discussed.

PMID- 15570775
TI  - A review of surgical treatment for obstructive sleep apnoea/hypopnoea syndrome.
AB  - Surgical intervention and treatment of OSAHS and snoring has a considerable
      history, encompassing a number of operations all of which have the intention of
      reducing or by-passing the pharyngeal resistance that occurs during sleep. Review
      of the published literature presents some problems, however, due to the ethical
      difficulties of undertaking randomised controlled trials in surgery. Uncontrolled
      trials are less satisfactory due to the large 'regression to the mean' and
      placebo effects. However, there is a considerable body of literature available
      relating to surgical intervention.

PMID- 15570776
TI  - Epidemiology and prevention of unexpected in-hospital deaths.
AB  - INTRODUCTION: The medical literature has only documented the importace of adverse
      events in terms of patient outcomes and cost to the health service over the last
      decade. This review focuses on the incidence, risk factors and prevention on
      unexpected in-hospital deaths. DISCUSSION: The incidence of unexpected in
      hospital deaths in the two major retrospective studies was 0.5% and 0.8% of all
      hospital admissions. A prospective study of surgical patients documented an
      incidence of nearly 7.1%. The risk factors that have been associated with
      hospital death include: increasing age; non-elective operative procedure;
      negligence; human error and unstable bedside observations in the hours prior to
      death. Although a number of intreventions have been suggested to prevent
      unexpected in-hospital deaths, very few studies have been performed to determine
      effectiveness. In a single institution historical control study, the introduction
      of a Medical Emergency Team was associated with 50% reduction in the casemix
      adjusted incidence of in-hospital cardiac arrest calls. CONCLUSION: There are a
      number of studies to suggest that in-hospital deaths are both predictable and
      preventable. More work is required to determine effective strategies to manage
      this problem.

PMID- 15570777
TI  - KTP laser fine fenestra stapedotomy with vein graft interposition in the surgical
      management of otosclerosis.
AB  - Otosclerosis is an hereditary disease of bone derived from the embryonic otic
      capsule. The exact aetiopathogenesis remains unclear. It can be associated with
      significant disability due to hearing impairment. Medical and surgical
      treatments, with varying degrees of effectiveness and complication rates, are
      available. The surgical method for the correction of the conductive hearing loss
      associated with otosclerosis continues to undergo technical refinement with the
      aim of improving results and minimising complications. The surgical technique of
      fine fenestra stapedotomy is well established. Here, we describe a new
      modification of this technique involving the use of a KTP laser. Based on the
      retrospective review of the results and complication rates of over 200
      consecutive cases, we would like to recommend the technique of KTP laser fine
      fenestra stapedotomy in the surgical management of otosclerosis.

PMID- 15570778
TI  - Mirizzi syndrome: a diagnostic and operative challenge.
AB  - INTRODUCTION: Mirizzi syndrome (MS) is an unusual complication of gallstone
      disease. The majority of cases are not identified pre-operatively, despite
      advances in imaging techniques. MATERIALS AND METHODS: Eighteen cases of MS were
      treated between January 1997 and April 2002. The clinical presentation, modes of
      investigation, surgical management and outcome are retrospectively reviewed.
      RESULTS: There were 13 female and 5 male patients, with a mean age of 60 years.
      Seven patients presented with the classical Charcot's triad. Ultrasonography (US)
      was the first imaging investigation in 13 patients and computerised tomography
      (CT) in the other five cases. Eleven patients had a successful endoscopic
      retrograde cholangio-pancreatography (ERCP) carried out. Diagnosis of MS was
      arrived at in seven patients following pre-operative imagings. Overall, 11
      patients had Type 1 and seven patients had Type 2 MS. In the group with Type 1
      MS, nine patients underwent open cholecystectomy, of whom six had concomitant
      common bile duct (CBD) exploration for stones and one patient with biliary
      stenosis had a hepaticojejunostomy bypass. Laparoscopic cholecystectomy was
      attempted in two patients, with successful completion in one case. In the group
      with Type 2 MS, four fistulas were closed surgically, the other three had biliary
      bypass procedures. CONCLUSION: Mirizzi syndrome is an unusual condition that
      poses diagnostic and operative challenges to the surgeon. With a judicious
      approach during dissection and early recognition of its presence, bile duct
      injury can be avoided. Good outcome can be achieved with an appropriate surgical
      procedure.

PMID- 15570779
TI  - The role of the intra-aortic balloon pump counterpulsation (IABP) in emergency
      surgery.
AB  - Elective surgical procedures are often delayed for up to six months in patients
      who have suffered a myocardial infarction (MI) because of the substantial risk of
      re-infarction and high peri-operative mortality. The optimal management of
      patients who have sustained a recent myocardial infarction and who require an
      emergency abdominal operation, however, has yet to be defined. The use of an
      intraaortic balloon pump (IABP) may play a role in such patients by improving the
      function of the injured heart. Three cases are presented in which IABP was used
      in patients who had recently sustained a myocardial infarction and who required
      emergency abdominal surgery. A review of the literature is presented and the
      application of IABP in such circumstances is discussed. Although clinical
      experience is limited, the use of the IABP may be useful in selected patients who
      have sustained a recent MI and who require emergency surgery.

PMID- 15570780
TI  - Bier's block using prilocaine: safe, cheap and well tolerated.
AB  - OBJECTIVES: To examine the safety of prilocaine Bier's block performed for Colles
      fracture manipulation, and assess patient satisfaction. METHOD: Fifteen-year
      retrospective review of all patients undergoing Colles fracture manipulation with
      a prilocaine Bier's block looking for the incidence of significant neurological
      or cardiovascular events. A confidential questionnaire was administered to 50
      consecutive patients to assess patient satisfaction with the method of
      anaesthesia. RESULTS: 1504 males with mean age 48 years and 5906 females with
      mean age 66 years received a prilocaine Bier's block for distal radial fracture
      manipulation. There were no documented incidences of anaphylaxis, arrhythmia,
      convulsions or collapse. Of 50 consecutive patients, all but two were satisfied
      with this form of anaesthesia. The pressure cuff inflation was considered the
      worst part of the procedure. CONCLUSION: Bier's block performed with prilocaine
      is at least as safe as other commonly used methods of anaesthesia for distal
      radial fracture reduction with high patient satisfaction. The procedure can be
      safely carried out by a single medical practitioner with appropriate patient
      monitoring and assistance from trained nursing staff.

PMID- 15570781
TI  - Granulomatous appendicitis.
AB  - Granulomatous inflammation of the appendix is uncommon. It can be caused by a
      variety of conditions, including systemic disorders such as Crohn's disease and
      sarcoidosis, and infections such as mycobacterium tuberculosis, yersinia
      pseudotuberculosis, parasites and fungi. Granulomatous appendicitis as an
      isolated pathological entity unassociated with systemic disease is rare. Isolated
      granulomatous inflammation of the appendix of unknown aetiology, otherwise known
      as idiopathic granulomatous appendicitis is extremely rare. Patients with this
      condition present with the typical signs and symptoms of acute appendicitis. We
      present a series of patients with isolated granulomatous inflammation of the
      appendix, and discuss the difficulties encountered in the management of this
      condition.

PMID- 15570782
TI  - The use of a mobile lithotripter in the treatment of tennis elbow and plantar
      fasciitis.
AB  - OBJECTIVE: To evaluate the use of the mobile lithotripter in the treatment of
      tennis elbow and plantar fasciitis. METHOD: A prospective single blind randomised
      trial was performed on 24 patients with tennis elbow and 23 patients with plantar
      fasciitis, with a mean duration of symptoms of 11 months. All patients had failed
      one or more method of treatment--conservative, topical non-steriodal anti
      inflammatory drugs (NSAID), steroid injection and/or surgery. The patients were
      divided into treatment and placebo groups. The placebo group received treatment
      with a clasp on the elbow/heel to stop penetration of shock waves. A baseline
      pain score was obtained using the Million Visual Analogue scale (0-10). The
      affected area was infiltrated with 3-5mls of 1% lignocaine. The treatment
      consisted of 2000 shock waves at 2.5 bars of air pressure with a frequency of 8
      10Hz. A total of three treatments were given at an interval of two weeks, each
      lasting for three to four minutes. RESULTS: In the treatment groups, a final pain
      score at six months post treatment showed significant improvement (three or more
      points) in 78% of patients with tennis elbow and 93% of patients with plantar
      fasciitis. In the placebo groups, significant improvement was seen in one patient
      (9%) with tennis elbow. The other patients in the placebo groups did not show
      significant improvement. This was statistically significant (chi square test) for
      both conditions. CONCLUSION: The mobile lithotripter is an effective way of
      treating tennis elbow and plantar fasciitis but warrants further larger studies.

PMID- 15570783
TI  - Acalculous biliary tract disorders: the value of fatty meal-cholescintigraphy.
AB  - BACKGROUND: The management of patients with symptoms consistent with biliary
      tract disease but without evidence of cholelithiasis is difficult. This study was
      undertaken to test the value of cholescintigraphy in predicting the success of
      cholecystectomy in patients with acalculous biliary tract disorders. MATERIAL AND
      METHODS: A prospective study was carried out on 73 patients presenting with
      recurrent upper quadrant pain without documented evidence of gallstones on
      ultrasound. Fatty meal-cholescintigraphy was performed on all patients and the
      gallbladder ejection fraction was calculated. Laparoscopic cholecystectomy was
      performed in patients with ejection fractions of <40%, followed by
      histopathological analysis and assessment of symptomatic improvement. RESULTS:
      There were 43 men and 30 women with a mean age of 33.4 years. Forty-one patients
      had abnormal ejection fractions. All except one patient had a laparoscopic
      cholecystectomy. The pathological diagnosis of chronic cholecystitis was made in
      33 patients and acute on chronic cholecystitis documented in four patients. Five
      patients had cholesterolosis and two of these had associated chronic
      cholecystitis. All except three patients had complete relief of symptoms post
      operatively with a mean follow-up of 10 months. CONCLUSION: Modified
      cholescintigraphy is a useful test for predicting which patients with acalculous
      biliary tract disease benefit from a cholecystectomy.

PMID- 15570784
TI  - Pharmacological prevention of cardiac risk in claudicants with ischaemic heart
      disease.
AB  - BACKGROUND: Claudicants rarely progress to critical limb ischaemia but have a
      threefold increase in mortality, mainly due to cardiac disease. Antithrombotic
      therapy, beta blockers, ACE inhibitors and statins have been shown to reduce
      mortality and cardiovascular morbidity in patients with ischaemic heart disease.
      AIM: To investigate secondary pharmacological prevention of ischaemic heart
      disease in claudicants. MATERIALS AND METHODS: We prospectively recorded
      comorbidity and drug treatment in 89 patients (67 men and 22 women) with a
      history of ischaemic heart disease recruited in a supervised exercise and
      lifestyle modification programme to improve claudication distance and prognosis.
      RESULTS: Of the 89 cases, 40 had a history of angina only and 49 of myocardial
      infarction. Sixteen (18%) had diabetes, 47 (53%) had hypercholesterolaemia and 52
      (58%) were hypertensive. Antithrombotic therapy was prescribed to 61 patients
      (68.5%), 64 (72%) with a history of myocardial infarction and 27 (67.5%) with
      angina only (p = 1). Beta-blockers were prescribed to 12 (13.5%) patients only,
      seven (15%) with a history of myocardial infarction and five (12.5%) with angina
      only (p = 1). Of the 47 patients with hypercholesterolaemia, 29 (62%) were on a
      statin. CONCLUSION: Secondary pharmacological prevention of ischaemic heart
      disease in claudicants remains suboptimal, with only two thirds of patients
      receiving antithrombotic therapy and a small minority receiving beta blockers.
      Pharmacological prevention in claudicants should improve to reduce cardiac
      morbidity and mortality.

PMID- 15570785
TI  - Primary aneurysm of the basilic vein.
AB  - This is a report of a 71-year-old woman who presented with a superficial soft
      tissue mass in the antecubital fossa. Excision was undertaken under local
      anaesthesia. The lesion proved to be a primary aneurysm of the basilic vein.
      Reviewing the literature we found only a few previous reports of primary venous
      aneurysms in the upper extremities.

PMID- 15570786
TI  - Counting health care: is there aF in CE?
AB  - The consultant episode is widely used by health economists as a measure of
      delivery of care. The clinical notes of 174 consecutive patients undergoing
      elective orthopaedic procedures were reviewed. Just over half of the cases
      (89/174, 51%) were patients referred by their general practitioner, but under
      half of the available operating time (47%) was expended on these patients, the
      remainder being on patients already within the system. Under standard NHS
      accounting, these latter patients are not registered as new consultant referrals
      and, thus, the episodes of patient care of which their operation is a part, do
      not constitute finished consultant episodes. Our view is that the episode of care
      is an inappropriate measure of health care delivery applied to orthopaedic
      surgery in general.

PMID- 15570787
TI  - Re: Alvarado score: an admission criterion in patients with right iliac fossa
      pain. Surg J R Coll Surg Edinb Irel 2003; 1: 39-41.

PMID- 15570788
TI  - Re: Alvarado score: an admission criterion in patients with right iliac fossa
      pain. Surg Jr Coill Edinb Irel 1; 2003(1):39-41.

PMID- 15570789
TI  - Re: The secret (GTN) of successful ERCP cannulation: a prospective randomised
      controlled study. J R Coll Edin 47 (4): 634-637.

PMID- 15570790
TI  - Kidney transplantation from non heart-beating donors.
AB  - The use of non heart-beating donor (NHBD) kidneys to expand transplant programmes
      offers an answer to the problem of donor shortage. This source of kidneys is
      utilised by very few renal transplant units despite longstanding and growing
      evidence of equivalent graft function and survival, compared with cadaveric donor
      organs. This article reviews the selection criteria, technical approaches and
      logistical organisation involved in NHBD kidney retrieval and transplantation and
      outlines the evidence for graft function and survival, and patient outcome. The
      ethical and legal implications of running a NHBD programme are discussed, and
      some areas of current and likely future research are covered.

PMID- 15570791
TI  - Arthroscopic meniscal repair.
AB  - Although the first meniscal repair was performed over 100 years ago, many aspects
      of meniscal repair remain controversial. This article reviews the structure and
      function of the menisci, the rationale for repair and the clinical results of
      arthroscopic meniscal repair.

PMID- 15570792
TI  - Selecting the best from the rest.
AB  - The current method for selecting surgeons of the future is neither objective nor
      relevant to present day needs. An assessment is needed which ranks potential
      trainees according to aptitude, motivation and diligence, all of which is
      validated. This task should be a core duty for the Royal Colleges of Surgeons
      working in close co-operation with surgical specialty associations.

PMID- 15570793
TI  - Primary total hip replacement.
AB  - Primary hip replacement requires careful patient selection, a knowledge of
      available prostheses, thorough pre-operative planning, familiarity with surgical
      exposures and sufficient manual dexterity to carry out the procedure. The aim of
      hip replacement is to restore the biomechanics of the diseased joint as closely
      as is practical. Failure to observe these principals results in premature failure
      of the joint replacement.

PMID- 15570794
TI  - Non-restorative surgery for rectal cancer: indications in 2003.
AB  - BACKGROUND: Although the majority of patients with low rectal tumours can now be
      offered restorative surgery, a subset of patients with very distal, locally
      extensive tumours, or excessive comorbidity, continue to require abdominoperineal
      resection or a Hartmann's procedure. The Clinical Standards Board for Scotland
      (CSBS) recommends that the permanent stoma rate for patients with rectal cancer
      should be no more than 40%. The aim of this study was to determine the proportion
      of patients not suitable for restorative surgery and to explore the remaining
      indications for non-restorative surgery. MATERIALS AND METHODS: Data pertaining
      to the management of 100 consecutive patients treated for a rectal adenocarcinoma
      were extracted from a prospective database. RESULTS: Eighty-one patients
      underwent primary restorative surgery; 12 patients, 9 of whom had received
      neoadjuvant therapy, had abdominoperineal excision for low rectal or anorectal
      tumours. Seven patients with locally extensive disease underwent an unplanned
      Hartmann's procedure rather than high anterior resection. Two of these resections
      were incomplete and two patients had metastatic disease not detected on staging.
      CONCLUSION: Not all patients with rectal cancer can avoid the formation of a
      stoma, but our results show that more than 80% of patients can be offered primary
      restorative surgery. The CSBS guidelines do not reflect acceptable contemporary
      practice and should be revised. This is particularly pertinent with the likely
      introduction of population screening for colorectal cancer.

PMID- 15570795
TI  - An assessment of surgeons' abilites to site colostomies accurately.
AB  - AIMS: The ability of surgeons to site a colostomy is assessed in a clinical
      model. In addition, the tuition received by surgical trainees in stoma siting is
      also reviewed. MATERIALS AND METHODS: Eleven surgeons (trainees--six, colorectal
      subspeciality interest--two) were asked to site an end colostomy on nine patients
      using an adhesive disc (diameter--1cm). The position of the stoma was then
      measured on the 'x' and 'y' axis of a 2cm box grid, (maximum error--1cm) which
      was placed on the abdomen and centred on the umbilicus. The positions were then
      compared with that chosen by the stoma nurse who was taken as the gold standard.
      Results were compared using ANOVA and the Mann Whitney--U test. A telephone
      questionnaire was then undertaken to review the training of junior surgeons.
      RESULTS: There was variance present within the group of surgeons studied
      (p<0.01). Trainees and consultants had a similar accuracy in stoma-siting
      (p<0.2). Consultants with a colorectal subspeciality interest were better at
      placing stomas than those with a general interest (p<0.002). Badly placed stomas
      were three times more likely to be too low than too high (p<0.002). Thirty of 37
      trainees reported receiving no undergraduate training from a specialist stoma
      nurse. Ninety per cent received postgraduate training from another surgeon while
      a specialist nurse trained only 35%. CONCLUSION: There was no difference between
      trainees and consultants in their ability to site a colostomy. However, surgeons
      with a subspeciality interest chose stoma sites that were more consistent with
      the specialist nurse than general surgeons. Training is haphazard and ability is
      frequently assumed rather than proven.

PMID- 15570796
TI  - An audit of the implementation of guidelines in relation to the prevention of
      dental caries.
AB  - AIM: To determine the implementation of national clinical guidelines in relation
      to the targeted prevention of dental caries in the permanent teeth of 6-16-year
      olds presenting for dental care amongst training grade staff working within the
      Hospital Dental Service. METHODS: Patient records were reviewed prospectively
      with regard to caries risk assessment, behaviour modification and tooth
      protection. Following dissemination of the results and reinforcement of
      fundamental points from the guideline, a second audit was conducted one month
      later. The results were assessed by chi2 (chi2) analysis. RESULTS: One hundred
      patient records were reviewed in both Audit One (M:52; F:48) and Audit Two (M:61;
      F:39). Caries risk assessment was poorly recorded in both Audits One and Two (13%
      and 17%, respectively). There was an improvement in radiographic reporting
      between the first and second audit, from 53% to 80% (chi2 = 16.36, P = 0.001).
      Dietary advice and toothbrushing instruction were recorded in 36% and 41% of
      records in Audit One, whilst in Audit Two this had improved to 68% and 92%,
      respectively (chi2 = 20.51, P = 0.001 and chi2 = 58.38, P = 0.001). There was a
      statistically significant improvement in the prescription of fissure sealants in
      Audit Two (chi2 = 38.97, P = 0.001), although not in the prescription of topical
      fluoride application (chi2 = 1.71, P = 0.192). CONCLUSION: Amongst training grade
      staff, there appears to be failure of implementation of certain aspects of SIGN
      guidelines for caries prevention. Clinical audit, however, would appear to
      improve guideline implementation.

PMID- 15570797
TI  - Re: A simple technique for the retention of a subcuticular suture. Singh-Ranger
      D. Surg J R Coll Surg Edinb Irel 2003; 1 (3): 149-51.

PMID- 15570798
TI  - Re: A simple technique for the retention of a subcuticular suture. Singh-Ranger
      D. Surg J R Coll Surg Edinb Irel 2003; 1 (3): 149-51.

PMID- 15570799
TI  - Re: General surgery units, asymptomatic gallstones and benign prostatic
      hypertrophy.

PMID- 15570800
TI  - Dissecting the molecular mechanisms of human cancer: translating laboratory
      advances into clinical practice.
AB  - There are multiple molecular mechanisms involved in human cancers with many genes
      involved, complex interactions and a variety of ways to examine them. Some events
      are already emerging as clinically important; others will turn out to be
      bystanders. By focussing on key genes, such as p53, the clinical implications of
      genetic changes and the pathways they link into are becoming apparent. Using the
      complex methodologies now available allied to disciplines such as mathematics we
      are improving our understanding of malignancy. This is beginning to impact on the
      management of patients with cancer; meanwhile, a good surgical operation
      performed timeously is still the best chance a patient has of a cure for most
      types of solid cancers.

PMID- 15570801
TI  - Surgical management of head and neck malignancy.
AB  - More than 90% of head and neck tumours are squamous cell carcinomas. This review
      focuses on tumours arising from the mucosal surfaces of the upper aerodigestive
      tract. We discuss the aetiology, presentation and investigation of these tumours
      and give special attention to their management which may comprise surgical
      resection, chemoradiation or combined therapy. The surgical treatment of the
      clinically positive neck and the somewhat controversial topic of management of
      the N0 neck are also discussed.

PMID- 15570802
TI  - Pain measurement in humans.
AB  - Sound measurement, an essential component of any scientific discipline, remains a
      particular problem in pain research. The measurement of pain intensity, for
      example, is a difficult and often a subjective undertaking. This is of little
      surprise to clinicians and researchers, because it is well recognised that pain
      intensity, like other sensations and perceptions, is a private experience that
      displays considerable variability both across patients and within a patient
      across time. Nonetheless, pain measurement and discerning factors that may affect
      its measurement are important for diagnosis and to determine the effectiveness of
      treatment interventions. This article reviews the basic concepts, roles,
      instruments used, and factors affecting pain measurement. A variety of the most
      commonly used pain measurement instruments are evaluated for their advantages and
      disadvantages. The article aims to assist clinicians and researchers to select
      the pain measurement instruments that best serve their purposes.

PMID- 15570803
TI  - Assessment at the end of training--a necessity nuisance.
AB  - If the public are to be assured that surgeons are safe, then there must be some
      form of competence assessment on which a licence to practice is based. However,
      the assessment and the licence needs to be both appropriate to the training
      received by the surgeon and to the requirements of the post they propose to take
      up. The 'key-concept' described in this paper attempts to address this problem.

PMID- 15570804
TI  - The three in one procedure: how I do it.
AB  - Recurrent patella dislocation is common, and selection of an appropriate
      stabilisation procedure is important for a successful outcome. We describe a
      combined proximal and distal realignment procedure to adjust soft tissue tension
      around the patella. This procedure, the 'Three in One' involves a combination of
      a lateral release, vastus medialis obliquus muscle advancement, and transfer of
      the medial third of the patellar tendon to the medial collateral ligament. This
      is a safe, reliable procedure for patients with recurrent dislocation of the
      patella resulting from an imbalance of soft tissue tension around the patella,
      but with a normally sited patella and normal trochlea.

PMID- 15570805
TI  - Autobanking of femoral heads for revision total hip replacement, a preliminary
      report of a new surgical technique.
AB  - BACKGROUND AND AIM: Conventional banking of bone allografts has been well
      documented in the literature. It relies on standardised screening and providing a
      sterile storage facility. We report a new surgical technique of banking the
      femoral head in a surgically fashioned subperiosteal iliac pouch and its use for
      the donor's own surgery. MATERIAL AND METHODS: Thirteen patients with an average
      age of 60 years and a diagnosis of osteoarthritis of the hip with a contralateral
      symptomatic loose hip replacement were selected. The femoral head was harvested
      and banked. On retrieval, histological analysis was performed in four specimens
      with clinical and radiographic review of all subjects. RESULTS: Radiographic
      results show good integration of the morselised femoral head bone graft in
      revision hip surgery. Histological results from four retrieved specimens show
      viability at eight years and eleven months from insertion into the pouch.
      DISCUSSION: Autobanking of the patient's own femoral head is suitable in a select
      group of patients in whom a combined primary and contralateral revision total hip
      replacement poses an unacceptable anaesthetic risk. It has the advantage of
      providing a graft with osteoinductive potential and a reduced risk of infection.
      It eliminates the need for a storage facility and screening programme. It also
      provides a portable storage facility if the patient moves elsewhere.

PMID- 15570806
TI  - An audit of 2273 ureteroscopies--a focus on intra-operative complications to
      justify proactive management of ureteric calculi.
AB  - BACKGROUND: At the national Stone Centre we have adopted a proactive management
      approach involving early ureteroscopy for ureteric calculi. As the efficacy of
      ureteroscopy is known this study focuses on the low intra-operative complication
      rate as justification for a proactive management protocol. PATIENTS AND METHODS:
      A retrospective study (1987-1997) identified 1936 patients undergoing 2273
      ureteroscopies. A database was created from inpatient hospital records. The male
      to female ratio was 3 to 1, age range was 25 to 84 years. RESULTS: Twenty-three
      patients (1%) had an intra-operative complication during ureteroscopy. Immediate
      ureteric JJ stenting was performed in 16 cases with ureteric injury. Two cases
      underwent percutaneous drainage and delayed antegrade ureteric stenting,
      ureteroscopy was terminated because of poor visibility. Five patients (0.22%)
      underwent open surgery for: ureteric perforation (n = 2); Dormia basket ureteric
      avulsion (n = 1); impacted Dormia basket and stone (n = 1); and impacted balloon
      dilator and stone (n = l). Ureteroscopic complications were not related to the
      level of ureteric calculus. CONCLUSION: A protocol of proactive management of
      ureteric calculi facilitates rapid turnover of large patient numbers. This
      approach is supported by the low intra-operative complication rate, most of which
      can be managed by further endoscopic procedures. In the event of corrective open
      surgery a favourable outcome has resulted.

PMID- 15570807
TI  - Management of congenital talipes equino varus in Scotland: a nationwide audit.
AB  - The Scottish Talipes Register is a record of all newly diagnosed cases of
      idiopathic congenital talipes equinovarus (CTEV) in Scotland over a four.year
      period. Two hundred and sixteen children were entered into the register, which
      recorded initial management and all subsequent interventions, both non-operative
      and operative. The data, therefore, represent a record of the different
      management regimens used within Scotland highlighting the variations in duration
      of conservative management and variations in surgical intervention following
      different methods of conservative management.

PMID- 15570808
TI  - Percutaneous drainage of spontaneous subcapsular haematoma of the spleen
      complicating chronic pancreatitis.
AB  - Subcapsular haematoma of the spleen is a rare complication of chronic
      pancreatitis. In the literature only a handful of cases have been documented. The
      exact aetiology and natural history of this complication remains speculative and
      its management controversial. A case of spontaneous subacute haematoma of the
      spleen in a patient with chronic relapsing alcohol-related pancreatitis was
      reported. A percutaneous drainage was performed with good outcome. A review of
      the literature has demonstrated only one previous similar report.

PMID- 15570809
TI  - Perforation of the terminal ileum: a possible complication of nicorandil therapy.
AB  - Recent reports have implicated nicorandil as a possible causative agent in the
      pathogenesis of anal and oral ulceration. We report a case of ulceration and
      perforation of the terminal ileum in a patient taking nicorandil. The possibility
      of an association between nicorandil therapy and gastrointestinal ulceration is
      discussed.

PMID- 15570811
TI  - Re: Myths of whiplash. Ferrari R. Surg J R Coll Surg Edinb Irel 2003. 1; 2: 99
      103.

PMID- 15570812
TI  - Re: Myths of whiplash. Ferrari R. Surg J R Coll Surg Edinb Irel 2003. 1; 2: 99
      103.

PMID- 15570813
TI  - Contribution of biomechanics, orthopaedics and rehabilitation: the past present
      and future.
AB  - Biomechanics is a field that has a very long history. From its beginnings in
      ancient Chinese and Greek literature, the field of orthopaedic biomechanics has
      grown in the areas of biomechanics of bone, articular cartilage, soft tissues,
      upper extremities, spine and so on. Bioengineers in collaboration with
      orthopaedic surgeons have applied biomechanical principles to study clinically
      relevant problems, improving patient treatment and outcome. In the past 30 years,
      my colleagues and I have focused our research on the biomechanics of
      musculoskeletal soft tissues, ligaments and tendons in particular. Therefore, in
      this review article, the function of the knee ligaments and the associated
      homeostatic responses secondary to immobilisation and exercise will be described.
      Research on healing of the medial collateral ligament (MCL) of the knee and
      possible future approaches in improving the healing of the knee ligaments will be
      presented. Finally, improvement of the understanding of ligament reconstruction,
      specifically of the anterior cruciate ligament (ACL), through the use of robotics
      technology will be included. Throughout the manuscript, specific scientific
      findings that have guided or changed the clinical management of injury to these
      soft tissues will be emphasised.

PMID- 15570814
TI  - Protean manifestations of intravenous drug use.
AB  - Intravenous drug use is an increasing social problem. Repeated venepunctures,
      injection of insoluble substances and needle sharing habits in intravenous drug
      users result in complications leading to admissions under various medical
      specialities. Many of these patients, however, manifest soft tissue wounds
      requiring specialised care from plastic surgeons. Typical presentations include
      injection site related abscess, cellulitis, necrotising fasciitis and non-healing
      wounds. We present a series of 11 consecutive cases treated in our unit over a
      six-month period, to highlight the varied clinical presentations and potential
      difficulties in their management.

PMID- 15570815
TI  - Intraspinal lumbar synovial cysts: diagnosis and surgical management.
AB  - BACKGROUND: Lumbar synovial cysts are a common association of facet joint
      degenerative disease. However, it is relatively rare for these cysts to cause
      symptoms of radiculopathy and nerve root compression. PATIENTS AND METHODS: We
      report a series of eight cases which were treated over a period of 20 months.
      There were five female and three male patients with a mean age of 66 years, and
      an average follow-up of seventeen months. All patients had pre-operative
      flexion/extension radiographs and MRI scans. Two patients had failed non-surgical
      treatment, two were associated with a Grade 1 spondylolisthesis, and all were
      associated with facet joint arthropathy. There were five cases occurring at L4/5
      and three at L5/S1. RESULTS: All patients underwent identical procedures, which
      involved exploration, hemi-laminotomy, flavectomy and minimal facet joint
      excision. No patient required posterior lumbar interbody fusion and at follow-up
      five patients had excellent and three had good results.

PMID- 15570816
TI  - An investigation into the relationship between the severity of obstructive sleep
      apnoea/hypopnoea syndrome and the vertical position of the hyoid bone.
AB  - OBJECTIVE: This study aimed to identify a correlation of diagnostic clinical
      significance between the vertical position of the hyoid bone in relation to
      structures within the dentofacial skeleton and: (1) The severity of obstructive
      sleep apnoea hypopnoea syndrome, (OSAHS), (2) Decisions relating to the
      management of the condition. DESIGN AND SETTING: Randomised retrospective survey
      of cephalometric records of subjects having been diagnosed as suffering with
      OSAHS by in patient overnight polysomnographic testing at the Edinburgh Royal
      Infirmary Sleep Centre, 2001-2002. MATERIALS AND METHODS: Pre-polysomnograph
      orthoposition lateral cephalograms of 94 subjects tested, during the period from
      April 1996 to September 1997, were randomly selected and traced following strict
      adherence to standard protocol. Edentulous arches (one or both) formed the only
      exclusion criterion owing to obvious effects upon vertical dimensions of the
      cervico-pharyngeal region. Measurement of the vertical position of the hyoid bone
      was made relative to a number of planes validated by numerous previous
      cephalometric investigations, and these were recorded along with the
      apnoea/hypopnoea index (AHI), and subsequent management (mandibular repositioning
      appliances (MRA) / continuous positive airway pressure (CPAP)). Correlations
      between measurements and AHI were investigated using Spearman's Correlation
      Coefficients, and analysis of the relationship between hyoid bone position and
      management groups was undertaken using Wilcoxon Ranked Sum Testing. DISCUSSION
      AND RESULTS: Statistically significant correlations were found between all linear
      measurements locating the hyoid bone in the vertical plane and subject AHI. The
      linear relationships were less reliable for subjects with AHI > 100, possibly due
      to a breakdown in the body's ability to respond posturally in order to maintain
      airway patency in more extreme cases. When the treatment groups (MRA/CPAP) were
      considered independently there was found to be a clear delineation between the
      two groups at a length of 120 mm between the sella (S- a point upon the anterior
      cranial base) and the hyoid (H). This, in turn, may suggest that cephalometric
      radiographs may be used as a reproduciable diagnostic tool.

PMID- 15570817
TI  - Efficacy and pitfalls of fine needle aspiration in the diagnosis of neck masses.
AB  - BACKGROUND: Fine needle aspiration biopsy (FNAB) is now well established in the
      assessment of cervical masses. The purpose of the present study is to review the
      efficacy of this procedure, as well as to identify any pitfalls that may limit
      its usefulness. METHODS: One hundred and ninety aspirations of neck masses
      performed over a recent five-year period were reviewed. The definitive diagnosis
      of the mass was determined in each case by review of the patients' case notes.
      RESULTS: Thirty seven per cent of all neck lumps were malignant. The most common
      cause for a false-negative result, in the case of a carcinomatous mass when an
      adequate sample had been obtained, was a cystic neoplasm. One quarter of all
      cystic lateral cervical masses not considered suspicious for malignancy by FNAB
      turned out to be malignant. CONCLUSION: Repeating FNAB in cases where the
      original result is negative for carcinoma may increase the sensitivity of FNAB in
      the detection of cystic carcinomas.

PMID- 15570818
TI  - Diagnostic conscious pain mapping using laparoscopy under local anaesthetic and
      sedation in general surgical patients.
AB  - BACKGROUND: Patients in whom extensive investigations have failed to identify the
      cause of abdominal pain present a challenge to surgeons. We present our initial
      experience of using laparoscopy under local anaesthetic and sedation in the
      diagnosis of chronic abdominal pain. METHODS AND PATIENTS: Nine patients with
      chronic abdominal pain and multiple normal investigations underwent laparoscopy
      under local anaesthetic and sedation. By touching and grasping intra-abdominal
      viscera and peritoneum, an attempt was made to reproduce the patient's pain.
      RESULTS: Two patients were found to have pain arising from the gall bladder and
      subsequently underwent laparoscopic cholecystectomy with resolution of their
      symptoms. A third patient had a clinical presentation of chronic acalculous
      cholecystitis and a normal laparoscopy. She decided to undergo laparoscopic
      cholecystectomy, which cured her pain. Another patient had pain arising from the
      appendix, which resolved after an appendicectomy. Three patients had pelvic
      adhesions, which caused chronic abdominal pain. After adhesiolysis, one is pain
      free; the others declined surgery for adhesions and their pain resolved.
      Conscious pain mapping was negative in two patients. CONCLUSION: Laparoscopy can
      be carried out in the conscious patient, who is then usually able to collaborate
      with the surgeon in establishing the source of the pain experienced during
      conscious pain mapping. Long-term effectiveness and diagnostic accuracy has not
      yet been established.

PMID- 15570819
TI  - Registrar operating experience over a 15-year period: more, less or more or less
      the same?
AB  - BACKGROUND: Concerns have been raised on the effects that recent changes in
      junior doctor work patterns may have on the breadth and depth of operative
      exposure achieved during specialist registrar training. This study aimed to
      determine whether there was any justification for these concerns by assessing
      whether there have been significant changes in either the number of cases or the
      case mix operated upon by registrars over the course of the past fifteen years.
      METHODS: A retrospective review of theatre records was undertaken, looking at the
      caseload of the registrars working for the same two consultant surgeons at one
      district general hospital in four one-year periods (1986-7; 1991-2; 1998-9; 2001
      2). The number, subspecialty, and time of each operation were recorded. RESULTS:
      Whilst operating experience for the first three periods of the study was static,
      the most recent assessment point has demonstrated a significant reduction in
      trainee routine operative experience and also a small reduction in the emergency
      workload performed by both firms. There was also a significant change in the
      elective case mixes corresponding to consultant sub-specialisation during this
      period. In addition, there were notable changes in the nature of the emergency
      workload and a reduction in the number of cases performed after midnight.
      CONCLUSION: SpRs trained during the Calman era appear to be gaining less
      operative experience than their predecessors in both the elective and emergency
      settings. With further changes in working patterns currently being implemented,
      major changes to SpR programmes are required if surgeons are to be adequately
      trained.

PMID- 15570820
TI  - Emergency general surgery and the implications for specialisation.
AB  - BACKGROUND AND PURPOSE: To examine the overall spectrum of emergency general
      surgical admissions and operations in Edinburgh, to identify the influence of an
      Accident and Emergency (A&E) department and observe the current practice of sub
      specialisation. PATIENTS AND METHODS: Data for all general surgical admissions
      and operations in the two main Edinburgh hospitals are recorded prospectively
      using the Lothian Surgical Audit system. These data were examined for 1999.
      RESULTS: 5346 patients were admitted to the two hospitals with acute surgical
      conditions. Head injuries (n = 1069, 20%) and Non Specific Abdominal pain (NSAP)
      (n = 855, 16%) made up a third of all emergency surgical admissions. The most
      common single category of operations were those done on the appendix (n = 348,
      15%). The Royal Infirmary, with the only A&E department had more acute surgical
      admissions (n = 4071) than the Western General Hospital (n = 1275), surgeons in
      the Royal Infirmary also operated on a much lower percentage of patients (30% v
      55%). In the Royal Infirmary, upper gastrointestinal surgeons treated a
      significantly higher proportion of patients with upper gastro-intestinal and
      hepatobiliary/pancreatic conditions than either the general or colorectal
      surgeons and, similarly, the colorectal surgeons treated a higher proportion of
      patients with colorectal conditions than either the general or upper gastro
      intestinal surgeons. CONCLUSION: The spectrum of emergency admissions and
      operations in Edinburgh is consistent with previously published data. An A&E
      department alters the spectrum of diagnoses and, therefore, the overall workload.
      Specialisation in emergency surgery is already quite advanced. These results all
      have important implications in future healthcare planning.

PMID- 15570821
TI  - MRSA in patients presenting with femoral fractures.
AB  - AIM: To assess MRSA carrier status in patients from different residences
      presenting with femoral fractures and to assess the incidence of MRSA deep wound
      infections post-operatively with regard to MRSA status on presentation. METHOD:
      One hundred and five patients were screened for MRSA on arrival over a 20-week
      period. They were then followed up post-operatively to determine the number of
      patients developing MRSA deep wound infection. RESULTS: One out of three patients
      came from an institution (nursing, residential home or hospital). Nearly one in
      four of these patients were MRSA carriers, compared with a carrier rate of less
      than 1 in 20 in patients admitted from home. Of the 11 cases presenting as MRSA
      carriers, two developed a MRSA deep wound infection, compared with 2 out of the
      94 patients not colonised with MRSA (X2 p < 0.01).

PMID- 15570822
TI  - Pyloric stenosis: unusual presentations and rare assoclations.
AB  - Pyloric stenosis is a common paediatric surgical condition with a well-recognised
      pattern of clinical features. Diagnosis is usually straightforward and a Ramstedt
      pyloromyotomy is curative. We present three patients who developed pyloric
      stenosis incidentally during the management of other primary surgical conditions.
      Issues of diagnostic difficulty following presentation of pyloric stenosis in the
      post-operative period (all three patients), its rare syndromic associations (one
      patient) and its management in this unusual situation are discussed. An awareness
      of the unusual presentations of pyloric stenosis during treatment for other
      primary surgical conditions can help in earlier diagnosis and treatment.

PMID- 15570823
TI  - Calycoureterostomy: a novel technique for post-renal transplant stricture.
AB  - Stenosis and necrosis of the ureter are amongst the severe complications after
      renal transplantation. Several surgical techniques like simple nephrostomy or
      native pyeloureterostomy using the native ureter have been applied for repair. We
      report a case of modification to the conventional pyeloureterostomy where the
      native ureter was anastomosed to the transplant calyx to restore continuity of
      the urine collecting system. This technique is recommended as a feasible
      alternative when secondary reconstruction by native pyeloureterostomy is not
      possible.

PMID- 15570824
TI  - Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of
      cervical lymphadenopathy.
AB  - Both Head and Neck Surgeons and General Surgeons are frequently referred patients
      with cervical lymphadenopathy. An uncommon but important cause is histiocytic
      necrotising lymphadenitis. This is a benign self-limiting disease that has been
      confused with malignant lymphomas. Some patients may also experience distressing
      and debilitating symptoms which can last for months. We describe four cases to
      illustrate the varied clinical presentation of this disease and present new signs
      seen in association with it. A remarkable therapeutic response to a short course
      of oral corticosteroids was observed in one case.

PMID- 15570825
TI  - Re: Bier's block using prilocaine: safe, cheap and well tolerated. Surg J R Coll
      Edinb Irel 2003; 1(5):283-5.

PMID- 15570826
TI  - Re: Bier 's block using prilocaine: safe, cheap and well tolerated. Surg J R Coll
      Edinb Irel 2003; 1: 283-285.

PMID- 15570827
TI  - Immunological aspects of head and neck cancer: biology, pathophysiology and
      therapeutic mechanisms.
AB  - Advanced cancer and head and neck cancer, in particular, remains a major clinical
      challenge with its associated morbidity and inevitable mortality. Local control
      of early disease is achievable in many solid tumours with current surgical and
      radiotherapeutic techniques but metastatic disease is associated with poor
      outcome and prognosis. It is known that, by the time of presentation, many
      patients will already have occult microscopic metastatic disease, and surgery and
      radiotherapy will not result in long-term survival. What little effect modern
      chemotherapeutic agents have on microscopic disease is, however, limited by
      systemic toxicity and multi-drug resistance. Immune surveillance is postulated to
      be operative in man. There is evidence, however, that patients with progressive
      tumour growth have failure of host defences both locally and systemically.
      Various possible defects and tumour escape mechanisms are discussed in the
      review. Immunotherapy and, in particular adoptive T cell therapy and DC therapy,
      show promise as putative tumour-specific therapy with clinical benefits. These
      techniques are undergoing development and evaluation in phase 1 clinical trials.
      Preliminary data suggest that the treatments are well tolerated. Unfortunately,
      there is limited evidence of significant and prolonged improvements in clinical
      outcome. Further developments of beneficial protocols (adjuvants, mode and
      frequency of vaccination etc) and multicentre studies of the use of immunotherapy
      in cancer are now required.

PMID- 15570828
TI  - Neglected rupture of the Achilles tendon: reconstruction with peroneus brevis
      tendon transfer.
AB  - The management of acute and neglected subcutaneous tears of the Achilles tendon
      by peroneus tendon transfer is safe but technically demanding. It affords good
      recovery, even in patients with a long-term neglected rupture. Patients with a
      neglected rupture are at a slightly greater risk of post-operative complications
      and may never fully recover their ankle plantar flexion strength.

PMID- 15570829
TI  - The mesenteric and antimesenteric location of colorectal cancer: the relationship
      with lymph nodes.
AB  - AIM: Purpose of the study was to evaluate if the circumferential location of
      colorectal cancer may be identified as a possible prognostic factor. The
      hypothesis is that tumours located on the antimesenteric (AM) side could have a
      better prognosis than tumours located on the mesenteric (M) side. METHODS: All
      patients undergoing curative resection for colorectal cancer were enrolled in the
      study. The specimens were sent to the pathologist to define the exact location of
      the tumour, the histological type, grading, T, N status as well as lymphatic,
      vascular and neural invasion, peritumoural lymphoid reaction, desmoplasia and
      microsatellite instability. Statistical analyses were performed using the test
      for proportions (with continuity correction), the Pearson Chi-square test and
      generalised linear models; p<0.05 were considered statistically significant.
      RESULTS: From August 2000 to August 2002, 255 patients were enrolled in the
      study. There was a significantly higher incidence of tumours located on the M
      (101) compared with the AM (37) site (p<0.0001). M located tumours were
      associated with higher numbers of metastatic lymph nodes (N1 and N2; p
      value=0.014), whereas AM tumours were associated with involved lymph nodes in
      only 5/37 (13.5%) of tumours. There was no statistically significant relation
      between AM versus M location and T status: the Pearson Chi-Square test showed
      that the lymph node involvement and the location (M versus AM) are not
      statistically independent variables (p-value=0.014). CONCLUSIONS: Our preliminary
      results show that when M or AM tumour identification is possible, tumour location
      can be regarded as a prognostic factor. Further longer studies on recurrence rate
      and survival are required to validate these findings and the clinical usefulness
      of this putative prognostic factor.

PMID- 15570830
TI  - Efficacy and safety peri-prostatic local anaesthetic injection in trans-rectal
      biopsy of the prostrate: a prospective randomised study.
AB  - OBJECTIVE: To assess the efficacy and safety of periprostatic lignocaine
      injection in trans-rectal ultrasound (TRUS) -guided biopsy of the prostate gland.
      METHODS: Ninety-six men (mean age 65 years, range 47-74) undergoing TRUS biopsy
      were randomised into the local anaesthetic (LA) or placebo group. Six to twelve
      biopsy cores were taken, the majority being 10 cores. Patients were asked to fill
      in the expected pain score on a visual analogue scale (VAS) prior to the
      procedure. They also completed the actual pain experienced on VAS after the
      biopsy. The incidence of complications was documented. RESULTS: The age, mean
      prostate specific antigen (PSA) were comparable in both groups. The expected pain
      score was also comparable (5.2 +/- 1.6 in LA, 5.0 +/- 1.4 in Placebo). In the LA
      group, the mean actual pain score was 3.0 +/- 1.8 and in the placebo group it was
      6.5 +/- 2.2 (P = 0.0001). When patients were asked whether they would undergo the
      procedure again in the same way, 100% of the LA group and only 64% of the placebo
      group responded 'yes' (P = 0.002 using Fisher's test). The complication rates
      were not significantly different between the two groups. CONCLUSION: Peri
      prostatic injection of local anaesthetic is safe and reduces discomfort
      significantly, and should be routinely offered to patients.

PMID- 15570831
TI  - Faecal incontinence in patients with anal fissure: a consequence of internal
      sphincterotomy or a feature of the condition?
AB  - BACKGROUND AND OBJECTIVE: The function of the internal sphincter is disturbed in
      patients with chronic anal fissure due to persistent hypertonia and it may lead
      to a certain degree of incontinence. Our aim is to assess the results of lateral
      internal sphincterotomy and to identify any degree of incontinence related to the
      disease. METHODS: This prospective study included a review of all patients
      operated upon by the authors who performed division of the internal sphincter at
      or below the upper limit of the fissure. A questionnaire was completed by each
      patient before surgery and then after surgery with regard to any degree of
      incontinence such as soiling of underclothes, control of flatus and accidental
      bowel motion. RESULTS: 126 patients with chronic anal fissure were studied. The
      male to female ratio was 0.8:1. Minor degrees of incontinence were present prior
      to surgery in 35 patients (28%) and in 31 (25%) patients after surgery, the
      majority of them were incontinent before surgery. CONCLUSION: Based on the
      results of this study, minor degrees of incontinence could be a symptom of
      chronic anal fissure and not the sequelae of lateral internal sphincterotomy.

PMID- 15570832
TI  - Total knee replacement and patellofemoral pain.
AB  - BACKGROUND: The decision to resurface the patella or not during total knee
      replacement (TKR) is a controversial issue. During primary TKR some surgeons
      routinely resurface the patella, others operate a selective policy and a third
      group never resurfaces the patella. AIM: This study attempts to investigate the
      relationship of patellofemoral knee pain and TKR. MATERIALS AND METHODS: This was
      a prospective, non-randomised, multi-centre outcome study of 638 primary Insall
      Burstein II total TKRs, and their effect upon patellofemoral pain. Of those
      enrolled 378 knees had pre-operative patellofemoral pain; 236 of these underwent
      patella resurfacing and 142 did not. There were no statistically significant
      differences in the post-operative incidence of patellofemoral pain between the
      groups treated with resurfacing of the patella and those in which the patella was
      left intact. In those knees that developed patellofemoral pain after TKR there
      was no significant difference as to whether the knee had had resurfacing done or
      not. CONCLUSION: Given that the cost of patella resurfacing is not insubstantial
      and that there are well-known complications resulting from it, we conclude that
      the role of patellar resurfacing for patellofemoral pain in knee arthritis
      remains unclear.

PMID- 15570833
TI  - Should we be concerned about diphtheria in the UK?
AB  - Diphtheria is a very rare condition in the developed world today with the advent
      of immunisation. Studies from the populations of England and Wales, however,
      suggest a recent increase in the number of notified cases. Sore throat due to a
      tonsillitis is the most common manifestation and can, thus, present to the
      clinician. It can also present as, or be complicated by, life-threatening upper
      airway obstruction. This case demonstrates the former and highlights the latter,
      in an attempt to raise awareness of a condition which may be seen more frequently
      in the future.

PMID- 15570834
TI  - Black pigmentation of bone due to long-term minocycline use.
AB  - Minocycline-induced dark pigmentation has been described affecting the oral
      cavity (teeth, mucosa, alveolar bone), skin, nails, eyes and thyroid. To date,
      there is no report of other bones being affected. We report a case of black
      pigmentation of the acromian in a patient who had used minocycline on a long-term
      basis for acne rosecea. Biopsy of the iliac crest revealed that the pelvis was
      also affected.

PMID- 15570835
TI  - Re: Molecular, clinical and political approaches to the problem of a cleft lip
      and palate. Surg JR Coll Surg Edinb Irel., 1: 2003; 9-16.

PMID- 15570836
TI  - Re: Selecting the best from the rest. Surg J R Coll Surg Edinb Irel. 2003: 1; 328
      331.

PMID- 15570837
TI  - Re: Selecting the best from the rest. Surg J R Coll Surg Edinb Irel. 2003: 1; 328
      331.

PMID- 15570838
TI  - Re: Dual mechanisms account for flame burns from surgical spirit ignited by
      diathermy. Surg J R Coll Surg Edinb Irel. 1: 2; 111-113.

PMID- 15570839
TI  - Selective histopathology of gall bladders is unscientific and dangerous.

PMID- 15570840
TI  - Selective histopathology of gall bladders is unscientific and dangerous.

PMID- 15570841
TI  - Re: Primary total hip replacement. Surg Jr Coll Surg Edinb Irel. 1: 6; 332-341.

PMID- 15570842
TI  - Major burn disasters: lessons to be learned from previous incidents and a need
      for a national plan.
AB  - The current concerns regarding possible terrorist actions throughout the world
      have to be considered to be now even more relevant to the UK. To date, there seem
      to be no official plans for Scotland other than those "major disaster incident"
      ones for each major hospital. These are not specifically designed to cope with a
      large-scale incident in which the majority of cases are burns. Such an event
      could swamp the local casualty and Burn Units. A model for possible
      consideration, based on a Dutch proposal, is put forward as being one that could
      be usefully applied to Scotland or, indeed, the UK.

PMID- 15570843
TI  - The role of gastrin in colorectal carcinogenesis.
AB  - Colorectal cancer is one of the leading causes of cancer-associated death in the
      United States and United Kingdom. In England and Wales, it is the second most
      common cancer in women and the third most common in men. Currently, treatment
      options for this debilitating disease are limited and surgical resection is the
      only curative treatment available. Despite rapid advances in surgery, as well as
      in adjuvant therapies such as radiotherapy and chemotherapy, there has been only
      a relatively modest improvement in mortality. The majority of colorectal cancers
      are epithelial-derived adenocarcinomas and arise from benign adenomas through the
      gain of mutations in key genes. Gastrin, an important polypeptide hormone,
      responsible for gastric acid secretion has been found to be involved in
      tumourigenesis in the gastrointestinal tract. When aberrantly expressed, the
      gastrin and gastrin/CCK-2 receptor genes can mediate powerful down stream events;
      the gastrin gene can impart anti-apoptotic properties while the gastrin/CCK-2
      receptor can activate the transcription of a number of factors including ligands
      of the epidermal growth factor (EGF) receptor, the REG protein and matrix
      metalloproteinases (MMPs). In colonic tumourigenesis, gene expression of both
      gastrin and the gastrin/CCK-2 receptor is activated within epithelial cells at an
      early stage of the adenoma-carcinoma sequence. This review details the role
      played by gastrin in the adenoma-carcinoma sequence of colorectal carcinogenesis.

PMID- 15570844
TI  - Perianal Crohn's disease and infliximab therapy.
AB  - INTRODUCTION: Perianal manifestations occur in almost half of patients with
      Crohn's disease and often respond poorly to conventional therapies. The
      introduction of anti-tumour necrosis factor alpha agents (e.g. infliximab) has
      altered the management of patients who fail first and second line medical and
      surgical therapies. METHODS: We performed a literature search of the PubMed
      database using the Medical Search Headings infliximab, perianal Crohn's disease,
      fistulae, cost and safety. We also performed a manual search using references
      from these articles, review articles and proceedings from major gastroenterology
      meetings. RESULTS: Use of infliximab, at a dose of 5mg/kg at intervals of 0, 2
      and 6 weeks, results in significant improvement in disease in approximately 70%
      of patients with fistulae. Prior examination under anaesthesia with placement of
      non-cutting seton sutures in fistula tracks is a useful adjunct in many patients.
      Preliminary results show a benefit from maintenance infliximab therapy and from
      concomitant use of immunosuppressants such as azathioprine. No clinical or
      biochemical markers have been identified which predict non-response to
      infliximab, although its use is contraindicated in patients with strictures.
      Acute infusion reactions are the most common side-effect of infliximab therapy
      and they are usually mild. Despite initial fears, the incidence of opportunistic
      infection is low. There is inadequate information, at present, regarding a
      possible increase in incidence of lymphoma with infliximab therapy. Infliximab is
      expensive compared with established therapies and its use will increase the
      lifetime cost of treating Crohn's disease. CONCLUSION: While infliximab is a
      useful adjunct in selected patients, the cornerstones of management of perianal
      Crohn's are essentially unchanged.

PMID- 15570845
TI  - Technique of suturing the mesh in laparoscopic total extra peritoneal (TEP)
      repair of inguinal hernia.
AB  - BACKGROUND AND PURPOSE OF STUDY: For laparoscopic repair of inguinal hernia,
      total extraperitoneal approach is the procedure of choice. The insertion of a
      mesh in laparoscopic total extraperitoneal repair (TEP) of an inguinal hernia
      with proper orientation and spreading it without wrinkles and folds in the
      preperitoneal space, however, is difficult to learn and carry out. Prolene mesh
      is also known to shrink and sometimes get displaced in the preperitoneal space
      giving rise to recurrences. We describe here an easy innovative technique of
      insertion of mesh and suture fixation. The surgeon has full control over the mesh
      and placement is accurate. METHOD AND RESULTS: One hundred hernias in 78 male
      patients were repaired. The same technique was used in all the patients and by
      one surgeon. In the technique, three midline ports were used. A dissection
      balloon and Tackers were not used. The mesh was fixed by sutures at the
      anatomical line joining the two anterior superior iliac spines with the help of
      suture hooks. There were no recurrences in 24 months of follow-up. There were no
      intraoperative complications. Mean operative time was 35 minutes. There was no
      conversion to an open or intraperitoneal approach. There was no incidence of mesh
      or wound infection. CONCLUSION: Many surgeons believe that the recurrence rate
      will increase when the mesh is not fixed. My technique of fixing the mesh is
      easily reproducible and economical. TEP with suturing the mesh is now my standard
      approach for inguinal hernia repair.

PMID- 15570846
TI  - Sentinel lymph node biopsy in breast cancer.
AB  - The sentinel lymph node (SLN) procedure consists of identifying the first lymph
      node to receive lymphatic vessels draining a tumour. Sentinel node biopsy is a
      minimally invasive technique, resulting in lower morbidity than traditional
      axillary lymph node dissection. Screen detected breast cancers are associated
      with approximately a 20% incidence of axillary node involvement. Sentinel node
      biopsy represents a minimally invasive method of accurately staging these
      patients.

PMID- 15570847
TI  - Anastomotic technique and survival after right hemicolectomy for colorectal
      cancer.
AB  - AIM: To compare the long-term outcome of patients after right hemicolectomy for
      colorectal cancer undergoing ileocolonic reconstruction either by a sutured
      technique or by side-to-side stapled anastomosis. METHODS: Single surgeon series
      from 1992 to 2001 comprising 100 consecutive patients, 59 with hand sutured
      reconstruction and 41 undergoing TLC 55mm stapled side-to-side anastomosis.
      Details of gender, patient age, and elective versus emergency presentation, Dukes
      stage, and curative versus palliative resection were recorded prospectively. In
      addition, post-operative hospital stay and subsequent survival were determined by
      prospective protocol follow-up. RESULTS: Overall 24% of the patients studied
      presented as emergencies and underwent a palliative procedure. There were no
      anastomotic leaks in either the stapled or sutured groups. Hospital mortality was
      also not significantly different--stapled reconstruction, 7%, sutured
      reconstruction, 10% (p value 0.624). Overall long-term cancer outcome was the
      same for both anastomotic techniques, both stapled and sutured groups having a
      median survival of 2.9 years. CONCLUSIONS: Stapled ileocolonic reconstruction
      after right hemicolectomy for colonic carcinoma is a safe and reliable surgical
      technique associated with long-term cancer outcomes comparable with those
      obtained by the sutured anastomotic technique.

PMID- 15570848
TI  - Fracture of the radial donor site after composite free flap harvest: a ten-year
      review.
AB  - The options for donor sites as a source of tissue for free vascularised
      osteocutaneous flaps are numerous, however, the radial forearm still has an
      important role. This series reports the largest published record of radial donor
      site fracture following the harvesting of osteocutaneous radial forearm free
      flaps used for reconstruction after ablative surgery for malignant disease. The
      relevant literature is reviewed. A retrospective review of cases treated using
      these flaps from 1991-2000 (inclusive) is carried out. Factors involved in the
      aetiology of fractures are discussed. Thirteen fractures are identified from
      seventy one osteocutaneous flaps (18%). A statistically significant majority of
      fractures occur in females. Limiting the percentage of radius diameter harvested
      is important and beveling of the osteotomy cuts may be advantageous in minimising
      weakening. Prophylactic plating of the donor site, particularly in the female
      patient, should be actively considered. The earlier the fracture occurs in the
      post-operative period, the more likely the need for operative intervention.

PMID- 15570849
TI  - Loop ileostomy: modification of technique.
AB  - INTRODUCTION: A loop ileostomy is a suitable procedure for faecal diversion. A
      number of technical improvements and advancement in stoma management have made
      its creation a suitable alternative to a loop colostomy. We describe an
      alternative technique for securing a loop ileostomy and perform a retrospective
      review of this technique. PATIENTS & METHOD: 40 patients who had a loop ileostomy
      performed as part of an abdominal procedure were reviewed. The loop of ileum was
      secured to the stoma site with a novel 'suture bridge' technique. RESULTS: 32
      patients had the stoma formed to protect a distal anastomosis, 6 to palliate
      bowel obstruction, 1 to control faecal incontinence and another for colonic
      Crohn's disease. There were no incidences of paralytic ileus, mechanical
      obstruction, prolapse, retraction or bleeding after the loop ileostomies were
      formed. Thirty patients had their ileostomies closed. In 27 patients this was
      performed by excising the muco-cutaneous edge and anterior closure. Three
      patients had their stomas resected and an end-to-end bowel anastomoses. Following
      closure there were two complications in separate patients--self-limiting
      paralytic ileus and small bowel obstruction at the site of the stomal closure
      that required a second operation. There were no incidences of anastomotic leaks
      or bleeding in patients who had their ileostomy closed. No mortalities were
      attributed to either stoma formation or closure. CONCLUSION: We have described a
      safe alternative technique for securing a loop ileostomy with negligible
      complications in construction and closure as demonstrated in our results.

PMID- 15570850
TI  - A case of subcutaneous myxopapillary ependymoma presenting as a pilonidal sinus.
AB  - We describe a rare neurogenic tumour presenting as a pilonidal sinus. This case
      illustrates the pitfalls associated with the management of a commonly occurring
      surgical condition. Pilonidal sinuses are often the province of trainee surgeons
      and while ependymomas are rare, this example emphasises the need to send the
      pilonidal sinus tract for histological examination.

PMID- 15570851
TI  - Re: Non-restorative surgery for rectal cancer: indications in 2003. O'Kelly TJ,
      Jansen JO. Surg J R Coll Surg Edinb Irel 2003,1,342-346.

PMID- 15570852
TI  - Re: Autobanking of femoral heads for revision total hip replacement, a
      preliminary report of a new surgical technique. Surg JR Coll Surg Edinb Irel.
      2004: 2; 37-41.

PMID- 15570853
TI  - Re: Perforation of the terminal ileum: a possible complication of nicrorandil
      therapy. Surg J R Coll Surg Edinb Irel. 2004: 56-57.

PMID- 15570854
TI  - Re: Perforation of the terminal ileum: a possible complication of nicorandil
      therapy. Surg JR Coll Surg Edinb Irel., 2 February 2004, 56-57.

PMID- 15570855
TI  - European working time directive and surgical training. An open letter to the
      Presidents of the Surgical Royal Colleges and Programme Directors of Higher
      Surgical Training.

PMID- 15570856
TI  - Re: A simple technique for the retention of a subcuticular suture. Surg JR Coll
      surg Edinb Irel. 2003:1; 149-152.

PMID- 15570857
TI  - Re: A simple technique for the retention of a subcuticular suture. Surg J R Coll
      Surg Edinb Irel. 2003:1; 149-152.

PMID- 15570858
TI  - Re: The use of a mobile lithotripter in the treatment of tennis elbow and plantar
      fasciitis. Surg JR Coll Surg Edinb Irel 2003;1: 290-2.

PMID- 15570859
TI  - Re: Assessment at the end of training--a necessity or a nuisance? Surg J R Coll
      Surg Edinb Irel., 2:2004; 28-31.

PMID- 15570860
TI  - Re: Assessment at the end of training--a necessity or a nuisance? C. Bulstrode, V
      Hunt Surg JR Coll Surg Edinb Irel 2:1,28-31.

PMID- 15570861
TI  - Re: Tissue engineering in surgery. Garner JP. JR Coll Surg Edinb Irel 2004; 2, 70
      78.

PMID- 15570862
TI  - Re: Anatomy: a must for teaching the next generation. J. Older. Surg J R Coll
      Surg Edinb Irel 2:2, 79-90.

PMID- 15570863
TI  - Re: Anatomy: a must for teaching the next generation. J. Older. Surg J R Coll
      Surg Edinb Irel 2:2, 79-90.

PMID- 15570864
TI  - [Clinical epidemiology: from the view points of science and ethics].

PMID- 15570865
TI  - [What is NASH?].

PMID- 15570866
TI  - [Histopathology of non-alcoholic steatohepatitis (NASH)].

PMID- 15570867
TI  - [Pathophysiology of NASH].

PMID- 15570868
TI  - [Treatment of nonalcoholic steatohepatitis (NASH)].

PMID- 15570869
TI  - [Evaluation of the efficacy of an Helicobacter pylori eradication treatment for
      idiopathic thrombocytopenic purpura patients].
AB  - The relationship between Helicobacter pylori (H. pylori) and gastric diseases
      (e.g. peptic ulcer, MALT lymphoma, and stomach cancer) has been widely accepted.
      Recent studies have also suggested an association between H. pylori infection and
      idiopathic thrombocytopenic purpura (ITP). In this study, an H. pylori
      eradication treatment was administered to 20 ITP patients and elucidated for its
      effectiveness. Among those 20 patients, H. pylori infection was confirmed in 17
      (85%) through a C14 urea breath test, a rapid urease test, or a culture
      examination of a biopsied sample obtained by gastrointestinal endoscopy. Although
      the other 3 were negative to H. pylori, the H. pylori eradication treatment was
      also attempted because no other effective treatments had been established at the
      time of this study. In the H. pylori eradication treatment, lansoprazole (LPZ) 60
      mg bid, amoxicillin (AMPC) 1500 mg bid, and clarithromycin (CAM) 400 mg bid were
      given to each patient for 7 days. For 4 cases, CAM was replaced with
      metronidazole (MNZ) 750 mg bid. The patients whose H. pylori infection was not
      eradicated after the first treatment received the re-eradication treatment with
      LPZ 60 mg bid, AMPC 1500 mg bid, and MNZ 750 mg bid for 7 days. After the
      treatments, the success of eradicating H. pylori was confirmed in all 17 H.
      pylori positive patients. In addition, platelet recovery was obtained in 11/20
      patients (55%), which included 2 H. pylori negative patients and 2 patients whose
      H. pylori eradication was not successful after the first treatment. No
      relationship was found between the eradication effectiveness and the following
      clinical parameters: age, gender, previous therapies, disease duration, presence
      of anti-nucleus antibody, endoscopic atrophic change in the stomach, or kinds of
      antibiotics used for the treatment. These results support the efficacy of an H.
      pylori eradication treatment for ITP patients. A noteworthy result of this study
      was that an increase of platelet count was observed not only in H. pylori
      positive ITP patients, but also in 2 out of 3 H. pylori negative ITP patients
      after H. pylori eradication. Further studies are required to elucidate the
      efficacy of H. pylori eradication therapy in the patients negative for H. pylori.

PMID- 15570870
TI  - [A case report of esophageal small cell carcinoma: a long-term survival by radio
      chemotherapy with carboplatin and etoposide].

PMID- 15570871
TI  - [A case of mesenteric inflammatory pseudotumor which had disappeared after
      incisional biopsy].

PMID- 15570872
TI  - [Malignant lymphoma of the pancreas with chronic hepatitis C].

PMID- 15570873
TI  - [A case of autoimmune hepatitis followed-up with an oral administration of
      ursodeoxycholic acid].

PMID- 15570874
TI  - [A case report of unresectable mesenteric malignant lymphoma with long survival].

PMID- 15570875
TI  - [Awake neurosurgery: usefullness of intraoperative cortical and subcortical
      functional mapping].

PMID- 15570876
TI  - [Endoscope-assisted microsurgery for intracranial aneurysms].

PMID- 15570877
TI  - [Clinical analysis of the patients with hemodialysis associated with
      intracerebral hematoma].
AB  - We treated 64 hemodialysis patients with cerebral hemorrhage over an 18-year
      period between 1986 and 2003. Clinical features, prognostic factors, and
      therapeutic strategy were reviewed in these cases. Thirty of the cases were in
      the 13-year period between 1986 and 1998, and 34 cases, in the 5-year period
      between 1999 and 2003. In recent years, the incidence of cerebral hemorrhage has
      risen with the increase in the number of hemodialysis patients. There were 21
      patients with at least a 10-year history of hemodialysis. The underlying cause of
      renal failure was diabetic nephropathy in 25 patients and glomerulonephritis in
      24 patients. The most frequent sites of bleeding were the basal ganglia and
      thalamus, the cerebellum being involved in only one patient. Many patients had
      severe bleeding with hematomas greater than 61 ml. Outcome assessment by the
      Glasgow Outcome Scale showed 24 patients with good recovery, 8 with moderate
      disability, 4 with severe disability, and 28 who died. Good recovery was seen
      more often in patients in their 50s and 60s, whereas death occurred more often in
      patients aged 70 and older. Although there is now less morbidity than previously,
      the prognosis is not uniformly favorable in all cases. Factors associated with a
      poorer prognosis included mixed hemorrhage, hematomas greater than 61 ml, and age
      70 and older. Hematoma size and age were particularly important prognostic
      factors. Improved management and prognosis in these patients requires acute
      intensive treatment similar to that for hypertensive cerebral hemorrhage.

PMID- 15570878
TI  - [Delayed epidural bleeding caused by traumatic pseudoaneurysm of the middle
      meningeal artery: case report].
AB  - A 16-year-old man who presented with delayed bleeding of epidural hematoma is
      reported. Computed tomography (CT) on admission demonstrated a small amount of
      right epidural hematoma and a small fracture of the right lateral orbital wall.
      He was treated conservatively. Repeated CT scans and magnetic resonance (MR)
      imaging revealed no growth in the epidural hematoma, but demonstrated flow void
      sign at the medial side of the hematoma on MR images. After 8 days, CT scan
      presented the regrowth of the hematoma, so we planned the removal of hematoma.
      Epidural hematoma due to the rupture of a traumatic pseudoaneurysm of the middle
      meningeal artery is rare. Especially, since traumatic lesions were diagnosed by
      CT, it was unusual to be able to diagnose the pseudoaneurysm of middle meningeal
      artery preoperatively. The cases of epidural hematoma treated conservatively
      should be followed up by MR imaging and MR angiography using the fat suppression
      technique.

PMID- 15570879
TI  - [A case of head injury accompanied by minute hemorrhage-like artifacts created by
      multislice CT scans].
AB  - We demonstrated a head injury case accompanied by multiple small high-density
      artifacts in the middle of the brain created by multislice CT scanning, due to
      the malfunction of a detector involved in reconstruction of the mid images. We
      named these objects high-density spot artifacts. The high-density spot artifacts
      resemble minute hemorrhages which appear as diffuse axonal injuries. Radiologists
      and neurosurgeons should be familiar with this the existence of artifact.

PMID- 15570880
TI  - [A case of a subclavian-vertebral junction arterial aneurysm with brain stem
      thromboembolism].
AB  - Subclavian artery aneurysm is relatively rare, but, we can scarcely find mention
      in the literature of a subclavian-vertebral junction aneurysm. We report a case
      of a 73-year-old man with a left subclavian-vertebral junction arterial aneurysm
      of 11 mm in diameter which caused a brain stem thromboembolism. He showed right
      hemiparesis and dysarthria on admission. On the 5th day after admission, his
      hemiparesis worsened and he could not even walk. In order to prevent further
      embolic attack on the vertebro-basilar system and rupture from the aneurysm, we
      embolized the aneurysm successfully with some GDC coils. During the operation, no
      further brain infarction occurred, and we maintained blood circulation in the
      left subclavian-vertebral artery. This aneurysm appeared on angiography to be
      atherosclerotic in its clinical characteristics, and we have scheduled follow-up
      angiography in two years time. As his hemiparesis had improved, he was discharged
      from the hospital on foot.

PMID- 15570881
TI  - [Multiple aneurysms of the distal posterior inferior cerebellar artery with
      recurrent hemorrhage undetectable on preoperative neuroradiological findings:
      case report].
AB  - We report a rare case of multiple aneurysms of the distal posterior inferior
      cerebellar artery (PICA) associated with recurrent hemorrhage undetectable on
      preoperative neuroradiological findings. A 68-year-old woman was admitted to our
      hospital in April, 2003 because of a sudden onset of headache, back neck pain and
      nausea. CT scan at the time of admission showed a hematoma in the 4th & 3rd
      ventricles, and a mild subarachnoid hemorrhage (SAH) in the basal, right ambient
      & quadrigeminal cisterns. She had had a similar history of previous
      intraventricular hemorrhage and SAH in October, 2001. Three-dimensional CT
      angiograms and left vertebral angiograms performed at that time revealed an
      irregular vascular lesion at the tonsillomedullary segment (TMS) of the left
      PICA. However, the final diagnosis was unclear. Left vertebral angiograms at the
      time of the 2003 admission revealed an irregular vascular lesion in the same
      region more clearly and the size of aneurysmal dilatations had increased
      considerably. So, preoperative diagnosis of an irregular vascular lesion at the
      TMS of the left PICA (distal PICA aneurysm was not ruled out) was based on the
      above neuroradiological findings. The patient was surgically treated through the
      suboccipital approach. The TMS of the left PICA had made a difficulty loop
      formation was observed. Five distinct aneurysma were found on the TMS of the left
      PICA. To prevent bleeding, the ruptured aneurysm & three unruptured aneurysms
      were clipped and the residual unruptured one was wrapped with Bemsheets.
      Postoperative left vertebral angiograms demonstrated neither clipped aneurysms
      nor occlusive findings at the TMS of the PICA. The patency of the PICA was
      preserved. The postoperative course was uneventful and the patient was discharged
      without new neurological deficits. There has been no rebleeding during the one
      year since surgery. The 23 reported cases of multiple aneurysms of the distal
      PICA including our case were reviewed and their neuroradiological and clinical
      features are discussed.

PMID- 15570882
TI  - [A case of lipomatous meningioma].
AB  - We present a case of a 55-year-old woman with intracranial lipomatous meningioma
      attached to the left sphenoid ridge. A CT showed a mass lesion partially with a
      hypodensity area in the left fronto-temporal lobe. On MRI, the mass lesion
      contained a hyperintensity portion on T1 weighted images, which changed to
      hypointensity on fat-suppressed-T1 images. Histological examinations demonstrated
      a transitional meningioma containing lipomatous portions. Immunohistochemical
      studies showed negative reactivity for epithelial membrane antigen (EMA) and
      positive reactivity for vimentin and S-100 in the areas with lipomaous foci. This
      pattern of reactivity was different from that of lipomatous meningiomas reported
      previously. Further examinations are needed concerning the origin of tumor cells
      in lipomatous meningiomas.

PMID- 15570883
TI  - ["How I do it" no. 8, dopa-resistant Parkinson's disease].

PMID- 15570884
TI  - Localization of Ulex europaeus agglutinin-I (UEA-I) in the developing gustatory
      epithelium of the rat.
AB  - To understand the development of the gustatory structures necessitates a reliable
      marker for both immature and mature taste buds. It has been reported that the
      intragemmal cells within the taste buds of adult rats were bound to Ulex
      europaeus agglutinin-I (UEA-I), a specific lectin for alpha-linked fucose, but it
      has not been determined whether immature taste buds, i.e. taste buds without an
      apparent taste pore, are labeled with UEA-I. The present study was conducted to
      examine the UEA-I binding pattern during the development of the rat gustatory
      epithelium. In adult animals, UEA-I bound to the membrane of taste buds in all
      examined regions of the gustatory epithelium. Within the individual taste buds,
      UEA-I labeled almost all intragemmal cells. The binding of UEA-I was occasionally
      detected below the keratinized layer of the trench wall epithelium but could not
      be found in the lingual epithelium of the adult animal. During the development of
      circumvallate papilla, some cells within the immature taste buds were also
      labeled with UEA-I. The developmental changes in the UEA-I binding pattern in
      fungiform papillae were almost identical to those in the circumvallate papilla:
      both immature and mature taste buds were labeled with UEA-I. The present results
      indicate that UEA-I is a specific lectin for the intragemmal cells of both
      immature and mature taste buds and, thus, UEA-I can be used as a reliable marker
      for all taste buds in the rat.

PMID- 15570885
TI  - Taste buds and nerve fibers in the rat larynx: an ultrastructural and
      immunohistochemical study.
AB  - We investigated the rat laryngeal taste buds and their innervation by electron
      microscopy and immunohistochemical methods. Taste buds were densely arranged in
      the surface facing the laryngeal cavity of the epiglottis, the aryepiglottic
      fold, and the cuneiform process of the arytenoid cartilages. The cells of the
      buds were classified into types I, II, III, and basal cells, the ultrastucture of
      which was almost the same as that previously reported in lingual taste buds. The
      type III cells that had synaptic contacts with nerve fibers were considered to be
      sensory cells. Immunohistochemical analysis revealed thick calbindin D28k
      immunoreactive fibers and thin varicose fibers immunoreactive for calcitonin gene
      related peptide or substance P in and around the taste bud. Serotonin
      immunoreactive cells were also observed here. The results revealed the
      innervation pattern of laryngeal taste buds to be the same as that in lingual
      taste buds. Carbonic anhydrase (CA) is known to catalyze the hydration of CO2 and
      dehydration of H2CO3, and seems to be essential in CO2 reception.
      Immunoreactivity for CAI was detected in slender cells and that for CAIII was
      observed in barrel-like cells in the laryngeal taste buds. The pH-sensitive
      inward rectifier K+ (Kir) channel in the cell membrane may be involved in CO2
      reception as well. CAII-reactive cells were also reactive to Kir4.1, PGP 9.5 and
      serotonin. Our results indicated that CAII and Kir4.1 are located in type III
      cells of the laryngeal taste buds, and supported the idea that the buds may be
      involved in the recognition of CO2.

PMID- 15570886
TI  - Mast cells and the inflammatory response to different implanted biomaterials.
AB  - The biocompatibility of dental materials is a topic of increasing importance for
      dentists. We investigated the effects of alloys for ceramic crowns and removable
      prostheses on the skin and lymphoid organs of rats. We used three groups of
      Sprague Dawley rats: group I as the control, with groups II and III implanted
      with different biomaterials into subcutaneous pockets. After sacrifice, the rat
      skin around the implant and the lymph nodes was studied. The tissues of implanted
      rats were morphologically different from the control animals as they showed a
      number of mast cells that increased 7 days after the implant with both alloys.
      These cells decreased 14 days after the implant with alloy for ceramic crowns
      whereas they were still high 28 days after the implant with alloy for removable
      prostheses. The findings suggest that both alloys induced different and time
      dependent inflammatory reactions. Our findings have importance in the future
      rational design of biocompatible implantable and blood-contact biomaterials.

PMID- 15570887
TI  - Localization of epidermal hyaluronan in the foot pads of the North American
      raccoon (Procyon lotor).
AB  - The localization of the epidermal hyaluronan in the digital foot pads of the
      North American raccoon (Procyon lotor) was examined by light and electron
      microscopic histochemical methods. The thick epidermis contained five epidermal
      layers composed of typical keratinocytes. In the stratum basale and stratum
      spinosum, hyaluronic acid was clearly detectable at cytoplasmic processes, in
      close vicinity to the surface coat of the plasma membrane, and/or in the
      intercellular space between the basal and spinous cells. The results suggest that
      epidermal hyaluronan that fills the intercellular space may particularly control
      water maintenance in the epidermis of the raccoon digital pads to guarantee the
      optimal mechanoreceptive function of the very specific and sensitive sensoric
      subepidermal equipment in this mammalian species.

PMID- 15570888
TI  - Age-related changes and the possible adaptability of rat jaw muscle spindles:
      immunohistochemical and fine structural studies.
AB  - Afferent signals from jaw muscle spindles contribute to the feedback mechanism
      that regulates mastication. The integrity and adaptability of this proprioceptor
      to age-related changes of the surrounding structures are therefore essential to
      maintain an appropriate masticatory function throughout life. In this study, we
      examined muscle spindles obtained from temporal and masseter muscles of 10-week-,
      12-, 18-, and 24-month-old Wistar rats, employing immunohistochemistry for
      protein gene product 9.5 (PGP 9.5) or growth-associated protein (GAP-43) in
      addition to transmission electron microscopy, in order to investigate their
      morphological changes in relation to the effect of aging on the adaptive
      potential of the receptors. Immunohistochemistry for PGP 9.5 showed virtually
      similar reactions at sensory nerve terminals in all age groups. On the other
      hand, immunoreactivity for GAP-43 in the sensory nerve ending of the muscle
      spindles was found 2 and 3 weeks after birth but became almost undetectable by 10
      weeks. However GAP-43 immunoreactions occasionally reappeared in those of
      spindles in 12- and 18-month old animals, and vanished again by 24 months of age.
      Electron microscopic observations also revealed age-related morphological changes
      in the intrafusal muscle fibers of the rats in 12-month and older groups. The
      extent of degenerative and/or atrophic alterations of intrafusal fibers increased
      with age and involved the nerve elements of spindles by 24 months. These findings
      indicate that the adaptation potential of rat jaw muscle spindles is well
      preserved until middle age, but diminishes in elderly animals. Structural changes
      of muscle spindles in elderly animals probably contribute to the deterioration of
      the muscular function.

PMID- 15570889
TI  - Neurotoxic morphological changes induced in the medial prefrontal cortex of rats
      behaviorally sensitized to methamphetamine.
AB  - The present study examined whether the development in rats of behavioral
      sensitization to methamphetamine (MAP) is related to the development of
      neurotoxic morphological changes presumably induced in the medial prefrontal
      cortex (MFC). Male rats were intraperitonieally injected with MAP (5 mg/kg) once
      a day for 12 days (day 1-day 12), and then the drug was withdrawn for 7-42 days
      (WD7-WD42). The MAP- treatment caused hypersensitivity of a successive head
      movement stereotypy, which reached a basic plateau level on day 4, and rose
      successively to a higher level by day 12. Morphological changes were
      histochemically and morphometrically examined in the MFC. In the strata covering
      layers II and III, the densities of tyrosine hydroxylase (TH)-immunoreactive
      axons decreased on a daily basis to 50% of the control on day 4 and then to 40%
      on days 6 and 12. The densities of dopamine-,beta-hydroxylase (DBH)
      immunoreactive axons did not change during the injection period. A few TUNEL
      positive cells were observed in a unit area (0.25 mm2) covering layers II-V on
      day 6 and they increased to 19 and 16 on day 12 and WD7, respectively. These
      observations demonstrate a role for the neurotoxic changes in the MFC in the
      processes of behavioral sensitization of a stereotypy to a low dose of MAP.

PMID- 15570890
TI  - Morphological changes in capillaries in the ischemic brain in Wistar rats.
AB  - The microvasculature in the brain plays a vital role in the maintenance of brain
      perfusion, and fulfills the dynamic requirements of normal brain functions. It is
      well known that collateral circulation can be induced by ischemia in cerebral
      infarctions, but it is not known whether cerebral ischemia affects
      microvasculatures in the ischemic region. In the present study, we examined
      quantitatively serial changes in capillaries following bilateral common carotid
      artery ligation in Wistar rats. After the animals were perfused with
      tetramethylrhodamine isothiocyanate-labeled gelatin 3 h (n = 9), 1 day (n = 9), 7
      days (n = 9) and 28 days (n = 9) after the ligation, capillary diameters in the
      brain sections were measured with a confocal laser-scanning microscope. Capillary
      diameters of the cerebellum did not differ among all groups, while those in the
      ischemic regions decreased significantly 3h after the ligation (p<0.01),
      thereafter gradually returned toward the baseline level, and became significantly
      larger (168% of the control) 28 days after the ligation (p< 0.01). The density of
      capillaries in the frontal and parietal cortices increased approximately to 1.3
      fold of those of the control level 28 days after the ligation. Transmission
      electron microscopy showed that the mean ratio of the inner diameter to the outer
      diameter of capillaries in the frontal cortex became significantly greater 28
      days after the ligation (p<0.05). Our data indicate that capillaries dilate in
      the ischemic brain region in the chronic phase of cerebral ischemia. It is also
      suggested that neovascularization occurs in the ischemic brain region.

PMID- 15570891
TI  - Cathodoluminescence imaging for identifying uptaken fluorescence materials in
      Kupffer cells using scanning electron microscopy.
AB  - Cathodoluminescence (CL) is the light that is emitted from a material irradiated
      by an electron beam. The present study was undertaken to show the applicability
      to biological studies of a scanning electron microscope (SEM) equipped with a
      high-sensitive cathodoluminescence detection system. For this purpose, we
      injected inorganic fluorescent powders (P43) suspended in phosphate buffered
      saline into rat blood circulation, fixed the animals with glutaraldehyde within a
      day, and observed the hepatic tissues with a SEM. Our instrument enabled the
      simultaneous collection of both secondary electron (SE) and CL images of these
      tissues. Backscattered electron (BSE) images of the same portion were also able
      to be obtained with this microscope. SE and BSE images clearly showed the three
      dimensional structure of the hepatic tissues including hepatocytes, Kupffer
      cells, Ito cells, and sinusoidal epithelial cells, while CL images visualized
      cathodoluminescence signals emitted from P43 as bright spots. We observed non
      coated tissues under a low-vacuum condition and metal-coated tissues under a high
      vacuum condition, and found that the high-vacuum observation of metal-coated
      tissues provided high quality CL images of P43 in the Kupffer cells. The
      superimposition of the CL images onto the corresponding SE or BSE images revealed
      that bright spots in the CL images were produced by the fluorescent powders
      uptaken by Kupffer cells. These findings indicate that the detection of CL as
      well as SE or BSE signals by SEM all provide us with useful information on the
      distribution of fluorescent tracers in tissues and cells in three-dimensional
      images.

PMID- 15570893
TI  - [Virus infection in renal transplant recipients].

PMID- 15570894
TI  - [Chronic rejection and chronic allograft nephropathy].

PMID- 15570895
TI  - [Functional analysis of the left-right determinant inv (inversion of embryonic
      turning) gene].
AB  - We identified the inv gene that encodes left and right asymmetry and regulates
      kidney development based on the information of the inv mutant mouse. However,
      functional properties and the modulator of gene expression of inv have been
      unclear. We used the tissue injury model for assessing the functional roles of
      inv in ischemia reperfusion injury (IRI). The kidney tissue taken from rats with
      IRI showed reciprocal changes in mRNA expression of inv: a 0.25-fold decrease at
      6 hours and then a gradual increase to a maximum 1.8-fold rise at 10 days of
      reperfusion. Next, oxidative stress was induced by exposing mouse inner medullary
      collecting duct (mIMCD-3) cells to hydrogen peroxide(H2O2) in the medium. Real
      time PCR showed that mRNA expression of inv decreased 0.52-fold at 3 hours with
      0.2 mM H2O2 in the medium, and then increased 3.1-fold at 24 hours with 0.1 mM
      H2O2 in the medium. RNA interference (RNAi) is a powerful tool to inhibit gene
      expression in experimental model systems. We knocked down inv gene expression in
      mIMCD-3 cells using RNAi to investigate the function of the inv gene. We designed
      a small interfering RNA (siRNA) to target the coding region of inv (inv-siRNA)
      and random-sequence scrambled siRNA(control siRNA). mIMCD-3 cells transfected
      with either the inv-siRNA or control siRNA were observed by microscopy. The cells
      transfected with inv-siRNA progressively lost cell-to-cell contact and the cell
      population significantly diminished approximately 48 hours post-transfection. The
      changes in gene expression profile were observed at time points (36 hours) using
      real-time PCR-based gene screening with categorized primer sets. Several genes
      related to structural protein of the matrix were downregulated. In contrast,
      repairing related genes were upregulated. In conclusion, gene expression of inv
      was modulated under oxidative stress and the inv gene may play a role in
      repairing and regenerating renal epithelial cells.

PMID- 15570896
TI  - [Role of androgens in the renal production of 20-hydroxyeicosatetraenoic acid in
      spontaneously hypertensive rats].
AB  - The role of androgens in the production of 20-hydroxyeicosatetraenoic acid (20
      HETE) was determined in the kidney of spontaneously hypertensive rats (SHR) and
      Wistar-Kyoto rats (WKY). The renal production of 20-HETE and blood pressure were
      higher in males than in females at 9 weeks of age. The renal production of 20
      HETE was significantly greater in male SHR than in male WKY, whereas it was
      significantly lower in female SHR than in female WKY. The differences in the
      renal production of 20-HETE were consistent with the cytochrome P-450 4A protein
      levels. Plasma free-testosterone levels in male SHR were twice as high as those
      in male WKY. Castration and treatment with the androgen receptor antagonist,
      flutamide, reduced blood pressure, the renal production of 20-HETE, and P-450 4A
      protein levels in both strains. The renal production of 20-HETE was significantly
      lower in castrated SHR than in castrated WKY. These results indicate that the
      renal production of 20-HETE and the expression of P-450 4A have gender and strain
      differences, and high levels of plasma androgens induce the expression of P-450
      4A and the production of 20-HETE in the kidney of male SHR. The androgen-induced
      production of 20-HETE may be associated with hypertension in male SHR.

PMID- 15570897
TI  - [Evaluation of renal damage using urinary ATP analysis].
AB  - It is reported that urinary ATP concentration analysis is useful for determining
      urinary tract infection and renal damage caused by drugs. By means of the firefly
      luciferin-luciferase method, we determined the reference value of urinary free
      ATP and evaluated the effects of urine sediments and conditions of storage. The
      reference value was established as 1.77 x 10(-10) to approximately 7.70 x 10(-9)M
      using urine samples obtained from 63 outpatients who seemed to have no renal
      disease. There was no significant difference in ATP concentration between 33
      males and 30 females. No significant changes were observed in 11 healthy
      volunteers during a 1-year period. Within-run reproducibility of ATP was
      satisfying (8.28% and 11.4% of coefficient value in low and high concentration
      samples, respectively). ATP concentration was significantly decreased after
      centrifugation (p < 0.05) and after filtration (p < 0.01). The amounts of the red
      blood cells (RBC) and white blood cells (WBC) in samples whose ATP concentration
      was decreased after centrifugation or filtration were significantly higher than
      those in samples whose concentration did not decrease (p < 0.05). Urine
      containing many RBCs and/or WBCs might show an artificially higher ATP
      concentration if no preparations has been performed. There were significant
      positive correlations between the ATP concentrations before and after
      refrigeration, but no correlations before and after freezing. It is concluded
      that the reference value of urinary free ATP concentration was 1.77 x 10(-10) to
      approximately 7.70 x 10(-9) M and that care is required in the estimation of
      urinary ATP concentrations in samples containing many sediments, especially with
      WBC and RBC.

PMID- 15570898
TI  - [Innate immunity in hemodialysis and continuous ambulatory peritoneal dialysis
      patients: impaired cytokine synthetic response to ex-vivo stimuli in mononuclear
      cells].
AB  - Dialysis patients are weak in immune host defense, which is associated with their
      high morbidity of infection. Polymorphonuclear leukocytes (PMNLs) and mononuclear
      cells play a key role in innate host defense. PMNLs and monocytes have
      bactericidal activity through the process of phagocytosis. Monocytes and
      lymphocytes contribute to the development of innate immunity by their cytokine
      actions. We studied the intracellular cytokine syntheses in response to ex-vivo
      stimuli, which may reflect the potential reactivity of immune cells in cytokine
      syntheses when pathogens invade humans. Furthermore, phagocytic activity was
      assessed in granulocytes and monocytes. Twenty HD, 15 CAPD, and 10 age-matched
      controls were enrolled in this study. One milliliter of whole blood from each
      subject was incubated with lipopolysaccharides (LPS) or mitogens for 4 hours at
      37 degrees C. Monoclonal antibodies to CD14+ and CD4+ were used for identifying
      monocytes and helper T cells, respectively. Intracellular cytokines were stained
      using FASTIMMUNE staining kits. Interleukin-1beta and TNF-alpha syntheses were
      examined in monocytes, which are the most important early-response cytokines in
      innate immunity. IFN-gamma and IL-4 syntheses were examined in helper T cells to
      observe their polarization into Th1 and Th2 cells. IFN-gamma is a key factor in
      establishing innate immunity. The percentage of cells that stained positive for
      each cytokine was analyzed using a flow cytometer. The following results were
      obtained: 1) In CAPD patients, IL-1beta and TNF-alpha response to LPS in
      monocytes were significantly reduced, as compared to other subjects. Polarization
      of helper T cells was reduced, resulting in a significant decrease in Th1 cells.
      2) In HD patients, monokine responses were not altered, but polarization of
      helper T cells was skewed toward a Th1 type. Phagocytic activities were not
      impaired in both dialysis groups. In conclusion, mononuclear cells from CAPD
      patients have the potential to exhibit failure of a cytokine response to ex-vivo
      stimuli in terms of innate immunity.

PMID- 15570899
TI  - [A case of chronic renal insufficiency due to vascular injury of systemic
      sclerosis].
AB  - A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was
      admitted to our hospital because of renal dysfunction. She had no hypertension at
      the time of admission and mild hypertension for only one and a half months until
      the time of admission. After admission, she received angiotensin-converting
      enzyme-inhibitor, but her renal dysfunction did not improve. She then had
      thrombotic microangiopathy with thrombocytopenia, and was treated with plasma
      exchange five times, but her renal dysfunction persisted. The renal biopsy
      specimens showed an arteriosclerotic lesion with intimal thickening and luminal
      narrowing and ischemic glomerular changes. These findings suggest that there is
      chronic vascular injury in a patient who has no hypertension with SSc and that
      once hypertension supervenes, whether severe or not, exacerbation of the vascular
      injury and renal dysfunction may occur.

PMID- 15570900
TI  - [A single case report of postrenal acute renal failure caused by pelvic and
      ureteral tumor composed of a mixture of transitional cell carcinoma and
      adenocarcinoma].
AB  - A 68-year-old woman was admitted to our hospital because of severe oliguria and
      macrohematuria. She was diagnosed as postrenal acute renal failure, because of
      bilateral dilatation of the renal pelvis on abdominal computed tomography (CT).
      Percutaneous nephrostomy was performed after hemodialysis was initiated. Next,
      urinary volume and serum creatinine level were normalized. Percutaneous biopsy
      towards the mass in the peritoneal cavity under abdominal CT revealed
      adenocarcinoma, although the primary site of the carcinoma could not be
      identified. Autopsy was permitted after her sudden death. It revealed that the
      primary carcinoma was a right pelvic and ureteral tumor. The right pelvic and
      ureteral tumor was composed of a mixture of transitional cell carcinoma and
      adenocarcinoma.

PMID- 15570901
TI  - [Two cases of autosomal dominant polycystic kidney diseases who presented
      bilateral enlarged kidneys and severe hypertension in the neonatal period].
AB  - Autosomal dominant polycystic kidney disease(ADPKD) is rarely observed in the
      neonatal period. We report 2 cases of ADPKD who showed bilateral enlarged,
      hyperechoic kidneys and severe hypertension. It is difficult to differentiate
      ADPKD from autosomal recessive polycystic kidney disease (ARPKD) based on the
      initial clinical presentations in this period. In both cases, bilateral enlarged
      kidneys and severe hypertension were detected without oligohydramnion and
      respiratory distress. The mother of case 1 has polycystic kidneys. The father of
      case 2 was diagnosed as ADPKD. Case 2 had heart failure due to hypertension.
      Angiotensin converting enzyme inhibitor (ACE-I) was administered to both patients
      and resulted in good control of blood pressure. ADPKD in the neonatal and very
      early infantile period has diverse clinical courses. In general, although severe
      cases are rare, some cases have renal failure and/or hypertension as we reported.
      We emphasize that both the prompt diagnosis of ADPKD and the start of medication
      are of great importance in the neonatal and very early infantile period. We
      recommend that neonates and infants with a family history of ADPKD undergo
      screening including physical examinations, blood pressure measurements and
      urinalysis.

PMID- 15570902
TI  - Get real. A virtual rehabilitation technology.

PMID- 15570903
TI  - Creating new balance. New concepts in gait and balance training are paving the
      way for successful treatment.

PMID- 15570904
TI  - Better lifts and transfers. A multi-channeled approach to lifts can ease the
      burden on caregivers and clients.

PMID- 15570905
TI  - Back in the saddle. Everything you ever needed to know about return-to-work
      programs.
AB  - Return-to-work programs and services can be effective methods in returning an
      injured worker back to their job. The primary objectives of return-to-work
      programs and services are to prevent work-related injuries and to successfully
      return an injured worker back to gainful and productive employment.

PMID- 15570906
TI  - Paying for power. A look at the costs associated with power-operated vehicles.
AB  - POVs may be the most appropriate choice for persons who are at risk of
      catastrophic injury, disability, or death should they be placed in a compromised
      position relative to their medical conditions. There is no panacea for
      successfully securing Medicare reimbursement particularly in light of coverage
      variations between DMERCs/intermediaries and the shifting sands of coverage
      policy. However, the guidelines outlined here may assist therapists who wish to
      serve as patient advocates in establishing the medical necessity of RT
      prescriptions.

PMID- 15570907
TI  - Theory into practice. Taking the latest research in arm rehabilitation and
      putting it to good use.

PMID- 15570908
TI  - Every minute counts. Therapists must learn to properly document the time spent
      actually treating each patient.

PMID- 15570909
TI  - One year later. A look at HIPAA a year after the implementation of the privacy
      rule.

PMID- 15570910
TI  - [Lung harvesting in Hungary--results of the first two years].
AB  - OBJECTIVE: Hungarian patients undergo lung transplantation within bilateral
      cooperation in Vienna, Austria since 1995. Lung harvesting was introduced in 2002
      in Hungary. Before 2002 Hungarian patients get 16 donor lungs from abroad, and 4
      patients died while being on the waiting list for transplantation. METHODS:
      Between 15/1/2002 and 31/12/2003 Hungarotransplant offered 164 potential lung
      donors to the Koranyi National Institute for Pulmonology. Donor selection was
      performed according to international guidelines. All operations were performed as
      part of multiorgan harvesting. Immediately before cross clamping the aorta 500
      microg epoprostenol (Flolan) was administered intravenously for opening the
      pulmonary vascular bed. The lung was perfused through the main pulmonary trunk
      with a single flush of 6 litre 4 degrees C extra cellular type low potassium
      dextran solution (Perfadex). During the perfusion both thoraces were cooled
      topical by 0.9% saline ice slush. After back table separation the donor lungs was
      packed and transported with topical cooling. RESULTS: The offer was refused in 27
      cases due to donor history, in 31 cases due to allograft pathology. In 57 cases
      the harvesting was not performed due to logistic reasons. Forty three donor lungs
      have been transplanted, 6 harvested lungs underwent only histopathology. From 43
      harvested lungs 41 bilateral and 3 single lung transplant procedures were
      performed. The mean cold ischaemic time (=CIT) was 3 75 +/- 50 minutes (range:
      230-560 min). Forty two donor lungs showed excellent primary graft function. One
      allograft underwent down-sizing lobectomy, where the histology of the specimen
      showed multiple microembolization, and signs of fibrosis, bronchiolitis and
      anthracosis. In this case the cold ischaemic time was 385 min. The patient needed
      an extracorporeal membrane oxygenation (ECMO) support immediately
      postoperatively, and died on the 4th postoperative day. After induction of lung
      harvesting in Hungary the average waiting time of Hungarian citizens dropped
      within one year from 14 +/- 8 weeks (range: 2-36 weeks) to 2.6 +/- 1.3 weeks
      (range: 1-4 weeks). In 2002 3 Hungarian patients died while being on the waiting
      list, their waiting time was 1, 1, and 7 days. In 2003 the waiting list mortality
      for Hungarian patients was 0%. CONCLUSIONS: After the introduction of lung
      harvesting both the waiting time and the waiting list mortality for Hungarian
      patients decreased. The potential yearly lung donor pool of Hungary is in the
      range of 5/1 million people.

PMID- 15570911
TI  - [Surgical complications of esophageal resections: our experience with 168
      operations].
AB  - We performed 346 operations for oesophageal cancer between 1 June 1991 and 31 May
      2001. 168 of them were resections. The resection rate was 48.5 percent. The most
      frequently performed operation was subtotal resection of the oesophagus with the
      removal of paraesophageal lymph nodes. Reconstruction was usually performed with
      gastric tube pulled up retrosternally according to Akiyama with cervical
      oesophago-gastrostomy (135/168). In 24 patients intrathoracic oesophago
      gastrostomy and in 9 patients other type of reconstruction was performed.
      Considerable co-morbidity was present in 88 percent of our patients (148/168).
      Alcohol dependency was noted in 88 patients however we suspect there were
      patients who did not admit alcohol abuse. Extended resection i.e. other organs'
      resection together with the oesophagus was performed in 59 patients.
      Postoperative recovery was uneventful in 49.4 percent (83/168) of our patients.
      Surgical complications occurred in 28.6 percent. Anastomotic leak was observed in
      21 cases (12.5 percent). The most severe complication was necrosis of an organ
      used in reconstruction (7 patients, 4.2 percent). 23 patients (13.7 percent) died
      in the postoperative period, 7 of them (4.2 percent) because of surgical
      complication. Statistical analysis proved that the R status and the extension of
      resection had no influence on the frequency of complications and mortality rate
      except for when the removal of the entire stomach or gastric stump was performed
      in one sitting with the oesophageal resection. The frequency of anastomotic
      leakage is grossly affected by the anastomosis technique and whether it was in
      cervical or in thoracic position.

PMID- 15570912
TI  - [Surgical treatment of malignant small bowel neoplasms--report on four cases].
AB  - About 0.3% of all malignancies and 2% of gastrointestinal tumours are malignant
      small bowel tumours. Many of these tumours are diagnosed during emergency surgery
      because of severe bleeding or acute intestinal obstruction. Planned surgical
      intervention if early and appropriate morphological and histological diagnosis is
      available offers lower short term complication rate and results in better
      longterm prognosis. We present the history of four patients operated on for
      malignant small bowel lesions between 1998 and 2002. We describe the
      possibilities and difficulties of diagnosis and surgical treatment of these rare
      gastrointestinal tumours.

PMID- 15570913
TI  - [Non septic, surgical complications and their treatment of acute necrotizing
      pancreatitis in 131 cases].
AB  - The authors analyse non septic, surgical complications and their treatment in 131
      patients with acute necrotizing pancreatitis. Bleeding occurred in 13 patients 16
      times. There were 3 cases with large intestine perforation, small intestine
      perforation twice in one patient and hydrothorax in 12 patients. The patients
      APACHE-II score was in the range of 15, 5, which was quite high. They experienced
      complications such as bleeding and bowel perforations mostly in those who
      underwent several reoperations. For the bleeding from acute duodenal ulcer
      conservative and surgical therapy (suturing) was executed. In the cases of
      intraabdominal bleeding they used several options such as, ligature, collagen
      mesh, Surgicell net and tamponation. Large intestine perforations were surgically
      treated with Hartmann's procedure or loop colostomy. The small intestine
      perforation was simply sutured. From the 12 patients with hydrothorax 8 underwent
      thoracic drainage. We lost 7 patients with bleeding, 3 with bowel perforations
      and 2 with hydrothorax. The authors believe that complications during therapy of
      acute necrotizing pancreatitis are high risk factor, but their treatment is not
      hopeless.

PMID- 15570914
TI  - [Laparoscopic resection of intraoperatively diagnosed parasitic cyst of the liver
      with the use of harmonic scalpel].
AB  - Echinococcus granulosus is one of the most important parasitic infections in the
      Mediterranean countries, it presents in the form of cystic lesions of the liver.
      During their development the cysts may cause various symptoms due to compression.
      Rupture of the cysts may lead to anaphylactoid reactions and/or to acute abdomen.
      We operated on a patient with symptoms of cholelithiasis and cholecystitis; she
      underwent laparoscopic cholecystectomy, during which a cystic tumour in the liver
      was accidentally detected. Successful laparoscopic pericystectomy was performed
      with Harmonic Scalpel. We are sure that laparoscopic resection of hydatid cysts
      is a safe option for a number of patients in the treatment of parasitic cysts of
      the liver.

PMID- 15570915
TI  - [Remembering a surgeon: Lipot Schischa (1885-1983)].

PMID- 15570916
TI  - [Treatment of atrial fibrillation with intraoperative radiofrequency ablation in
      one stage with valvular surgery].
AB  - Atrial fibrillation is the most frequent chronic arrhythmia, with significant
      cardiovascular morbidity and mortality risk. Poor remission rate with medical
      treatment and the outstanding efficacy of Cox-maze procedure inspired the less
      invasive intraoperative radiofrequency ablation therapy in patients undergoing
      open heart surgery. In June 2003 the first maze procedure in Hungary with the
      Medtronic Cardioblate surgical ablation system, with mitral and tricuspid
      valvuloplasty in a patient suffering from mitral and tricuspid insufficiency with
      paroxysmal atrial fibrillation, was performed in our institution. After 8 months
      the patient is in sinus rhythm and is free of complaints.

PMID- 15570917
TI  - [Significance of Toll-like receptors in the pathophysiology of surgical sepsis].
AB  - The discovery of Toll-like receptors has substantially changed our knowledge of
      pathogen recognition. 11 Toll-like receptors have so far been described in
      humans. These recognize distinct pathogen associated molecular patterns, as well
      as endogenous ligands and small molecular synthetic compounds. TLRs have a
      multifunctional role in pathogen-triggered immune responses and represent an
      important connection between the "innate" and "adaptive" immunity. The role of
      the TLRs in the recognition of pathogens renders them a key figure in the
      activation of the immune response during surgical sepsis. However, emerging
      evidence points to a fundamental role in tumorigenesis, transplantation, wound
      healing, atherogenesis and inflammatory bowel disease. The aim hence was to
      review experimental data pertaining to the activation of TLR signalling pathways
      in conditions associated with surgical sepsis. A systematic review of the
      literature was undertaken by searching the MEDLINE database for the period 1966
      2004 without language restriction. The paper also analyses the possible
      therapeutic utilization of the TLR signalling pathways in surgical sepsis.

PMID- 15570918
TI  - [In regard to gastric cancer treatment guidelines--a revised edition].
AB  - The Japanese Gastric Cancer Association issued a revised edition of gastric
      cancer treatment guidelines in April 2004. Distinctive features of this revision
      are adopting newly published literatures after the first edition of the
      guidelines, laparoscopy-assisted gastrectomy and perioperative management, and
      illustrating evidence levels in the clinical study of chemotherapy. The treatment
      protocol of the phase III study is an actual example of this. Gastric cancer
      treatment in Japan leads the world when considering operation and endoscopic
      treatment. However, there are only few controlled randomized clinical trials in
      Japan, and many low quality literatures. On the other hand, an evaluation of the
      consensus of gastric cancer treatment indicates that it is a high evidence level.
      Furthermore, a revised edition of chemotherapy was the only one that could be
      able to show a high evidence level. According to a questionnaire investigation of
      the revised guidelines, more than 90% of the respondents (the members of Japanese
      Gastric Cancer Association) have used the guidelines. Hence, the role of the
      guidelines is important.

PMID- 15570919
TI  - [Combination chemotherapy for gastric cancer including LV/5-FU].
AB  - LV (l-LV)/5-FU therapy has been used broadly and is considered to be a standard
      treatment for large bowel cancer due to an enhancing therapeutic effect of 5-FU.
      According to recent clinical study reports on large bowel cancer in Europe and
      the United States, various administration methods of LV/5-FU with a combination
      of other drugs have been devised. It appeared that 5-FU used together in bolus
      and continuous infusions have yielded outstanding results. Although the basis of
      combination therapy for gastric cancer seemed to be LV/5-FU, there were many
      reports on TS-1 combined with other drugs because the oral medicine TS-1 was
      domestically available for the past one or two years. Currently, controlled
      randomized trials of LV/5-FU therapy and TS-1 have been ongoing. However, when
      patients cannot take oral intakes, LV/5-FU therapy is important. It seems that
      LV/5-FU therapy in combination with other drugs, in particular, CDDP, CPT-11,
      paclitaxel, docetaxel, oxaliplatin, and ETP will be given as candidates for the
      standard treatment of gastric cancer.

PMID- 15570920
TI  - [Combination chemotherapy of TS-1 +cisplatin for inoperable gastric cancer].
AB  - There is no chemotherapy considered to be standard treatment for advanced gastric
      cancer worldwide, and there is no consensus as to whether combination or single
      agent therapy is preferred. In the phase I portion, a dose-escalation study of
      cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase
      inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated
      dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective
      response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40
      mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be
      given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the
      DLT. Treatment was repeated every 5 weeks, unless disease progression was
      observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2,
      because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore,
      the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients
      including 6 patients of the RD phase I portion were evaluated. The median
      administered courses was 4 (range: 1-8). The incidence of haematological and non
      haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but
      all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9
      (90.6%), and the median survival days were 383. This regimen is considered to be
      active against AGC with acceptable toxicity. In addition, currently, a randomized
      phase III study (JCOG 9912) for AGC patients not treated previously with
      chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone
      and CPT-11 with CDDP therapy. We also initiated a randomized phase III study
      comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we
      may be able to evaluate the clinical benefit of TS-1 in combination with CDDP
      versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival
      benefits and improving the QOL for AGC patients.

PMID- 15570921
TI  - [Combination therapy of a novel oral fluorouracil derivative TS-1 with low-dose
      cisplatin for recurrent and very advanced gastric cancer].
AB  - The case reports and clinical trials on combination therapy of a novel oral 5
      fluorouracil derivative TS-1 with low-dose cisplatin for gastric cancer were
      reviewed. In the majority of the case reports, TS-1 was administered at 80-120
      mg/body per day for 4 weeks followed by a rest of 2 weeks. However, in several
      case reports, TS-1 administration was slightly shortened such as 3 weeks
      administration followed by a rest of 2 weeks. The administration of cisplatin
      (CDDP) varied: every day, weekly, bi-weekly, and so on; the doses were from 1 to
      25 mg/m2. CDDP was mostly given at 5-10 mg/body 5 days per week, mimicking the
      low-dose FP (5-fluorouracil+ CDDP). In most case reports, combination therapies
      were undertaken on an inpatient basis due to frequent administration of CDDP,
      while the weekly or bi-weekly CDDP administration regimens were done on an
      outpatient basis. The case reports demonstrated high efficacies and few adverse
      effects of the combination therapy. Several case reports showed unresectable
      cases could be operated curatively after the combination therapy. There have been
      three phase I clinical trials, two of which were regimens on an outpatient basis.
      JFMC 27-9902, an inpatient-basis phase I clinical trial, consisted of TS-1 at 80
      mg/m2 every day and CDDP at low-dose for 5 days per a week: the regimen consisted
      of 4 weeks administration and 2 weeks' rest. The recommended dose of CDDP was
      determined to be 4 mg/m2 in the JFMC27-9902 regimen. In the modified JFMC27-9902
      regimen, CDDP was given twice a week on an outpatient basis. This new phase I/II
      clinical trial has been under way since 2003 December. In conclusion, TS-1 + low
      dose CDDP combination therapy will be done on an outpatient basis in future, and
      may be examined as a neoadjuvant therapy as well as a conventional form of
      chemotherapy.

PMID- 15570922
TI  - [A randomized phase II clinical trial of tailored CPT-11 + TS-1 vs TS-1 in
      patients with advanced or recurrent gastric carcinoma as the first-line
      chemotherapy (JFMC31-0301)].
AB  - The Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) has
      designed and initiated a randomized Phase II clinical trial planned as a first
      line of chemotherapy for advanced or recurrent gastric cancer. The trial focuses
      on two groups and selecting the better of two regimens. The first group was given
      tailored CPT-11, adjusting individual optimal dosage using toxicity-based grading
      as an index in combination with TS-1, and the second group was given standard TS
      1 treatment. The aim of this tailored dosage regimen for each individual patient
      is to continue chemotherapy as long as possible, and eventually, to prolong
      survival. In this trial, subsidiary pharmacokinetics analysis for the tailored
      arm is also proposed. We would like to introduce the significance and theory of
      tailored dosage chemotherapy in this paper.

PMID- 15570923
TI  - [CPT-11 combined chemotherapy for metastatic gastric cancer].
AB  - The effectiveness of chemotherapy for metastatic gastric cancer has been already
      revealed. But a standard chemotherapy has not been established yet. New agents
      such as TS-1, CPT-11 and taxanes are improving the response rates and also the
      survivals for gastric cancer. Including these new drugs, several randomized phase
      III trials are ongoing in Japan. In the near future, the candidate for standard
      resume will be sent abroad. In this article, we described the current state of
      CPT-11 combined chemotherapy for gastric cancer. Among various CPT-11- combined
      chemotherapy, CPT-11 + TS-1 is the most effective and less toxic treatment.

PMID- 15570924
TI  - [Current combination chemotherapy containing paclitaxel for advanced, recurrent
      gastric cancer].
AB  - 5-FU has been a key chemotherapeutic agent in the treatment of advanced or
      recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical
      modulation or combination chemotherapy has been developed. Although several phase
      III studies were reported in the 1990s, a standard chemotherapeutic regimen has
      not been established worldwide. Recently, a newly developed anticancer agent,
      Paclitaxel, can be clinically used for advanced gastric cancer either as a single
      agent or in combination with such as 5-FU, cisplatin, and TS-1. It may well
      further improve the quality of life and prolong the survival of patients with
      gastric cancer. Further assessment for the well design phase III clinical trials
      will be necessary to establish the availability of such combination modalities
      for the treatment of advanced, recurrent gastric cancer.

PMID- 15570925
TI  - [Combination chemotherapy of TS-1 and docetaxel on advanced and recurrent gastric
      cancer].
AB  - In the present article, we have summarized the clinical trials on docetaxel and
      the phase I study of docetaxel and combination therapy. Patients with a
      performance status (PS) of 0 to 2 received docetaxel at the starting dose of 40
      mg/m2 by iv infusion over 1 hour on day 1 and TS-1 at the full dose of 80 mg/m2
      daily for two weeks every three weeks. Nine patients were treated with increasing
      dose levels of docetaxel as follows: (docetaxel/TS-1, mg/m2): 40/80 (level 1),
      50/80 (level 2) and 60/80 (level 3), and all the cases were found to be
      assessable for drug safety, while 7 were assessable for response. The MTD was
      reached at the 50/80 mg/m2 dose level in three patients out of six, who
      experienced a dose limiting toxicity (DLT). On the other hand, partial response
      was achieved in 5 (71.4%) of the 7 patients with evaluable lesions. The drug
      combination showed a good safety profile, and the responses observed in the study
      suggest that the drug combination shows a high degree of efficacy in patients
      with advanced and or recurrent gastric cancer.

PMID- 15570926
TI  - [Clinical problems in gemcitabine treatment for unresectable pancreatic cancer in
      the elderly--a multicentric retrospective study of 53 cases].
AB  - In Gemcitabine treatment, elderly patients with unresectable pancreatic cancer
      are more likely to suffer from haematological and non-haematological adverse
      effects than non-elderly patients. Forty percent of the elderly patients were
      dropped from the initial protocol due to the adverse effects, mainly because of
      non-haematological events or symptoms. To avoid adverse effects, the
      administration schedule for Gemcitabine tended to be less often and at a lower
      dose for elderly patients among members of the Nagano Pancreatic Cancer Study
      Group. However, the fact that some cases showed a limited effect from this
      administration schedule albeit without adverse effect, might suggest that the
      frequency of ordinary administration schedule should be maintained, although the
      Gemcitabine dose could be decreased in unresectable pancreatic cancer patients in
      poor condition.

PMID- 15570927
TI  - [Concurrent chemoradiation using daily low-dose CDDP and UFT-E for postoperative
      recurrent esophageal cancers].
AB  - We reported concurrent chemoradiation for postoperative recurrent esophageal
      cancer patients with lymph node metastases and a pulmonary metastasis. From
      October 2001 to January 2004, we treated 6 consecutive patients with radiation
      and concurrent chemotherapy using daily low-doses of CDDP and UFT-E. Of the 6
      patients, 4 (67%) had a complete response and 2 (33%) a partial response,
      yielding an overall response rate of 100% (6/6). Five patients are now alive
      without cancers, and 1 patient died with cancer. Concurrent chemoradiation using
      daily low-doses of CDDP and UFT-E is feasible and seems to offer good results for
      recurrent esophageal cancer patients.

PMID- 15570928
TI  - [TS-1/CDDP/Lentinan combination chemotherapy for inoperable advanced gastric
      cancer].
AB  - It is reported that TS-1 administered orally shows a significant anti-neoplasm
      effect on advanced gastric cancer, and, furthermore, approximately 70% or greater
      effectiveness is reported for combination chemotherapy with cisplatin (CDDP).
      Lentinan is reported to extend the survival period in advanced cancer, and in
      combination with Tegafur. In the present study, combination chemotherapy with TS
      1/CDDP/Lentinan was conducted for patients with inoperable advanced gastric
      cancer, and the validity, safety and resultant QOL of the treatment were
      evaluated. TS-1 was administered for 3 weeks at 80 mg/m2, followed by withdrawal
      for 2 weeks, and CDDP was prescribed once for patients at 70 mg/m2 on the 8th day
      after starting TS-1 administration. For patients aged 80 or above, however, the
      dose was reduced, and given separately to the patients. Lentinan was administered
      at 2 mg/week. The rate of effectiveness for the 9 registered patients was 100%.
      This high rate was obtained regardless of changes in the histopathological
      findings. Critical side effects (grade three or above) were anemia and
      pigmentation, in one case each. An improvement in QOL was also observed for
      combination therapy including Lentinan. In cases of inoperable advanced gastric
      cancer, TS-1/CDDP combination chemotherapy showed higher efficacy regardless of
      the pathological alterations, and higher and sustained improvement of QOL was
      also observed with the addition of Lentinan to the protocol.

PMID- 15570929
TI  - [Evaluation of ten intravenous catheters for operability and safety in the
      infusion room].
AB  - We have a randomized trial to compare the operability and safety of ten 24-gauge
      intravenous catheters in the infusion room. In the present study, we used 3
      intravenous catheters without safety covers (Jelco plus, Surflo flash, Intima)
      and 7 intravenous catheters with safety covers (Supercath, Introcan safety,
      Surshield surflo II, Insyte autoguard, Safetouch cath, Protective plus, Acuvance
      plus). All catheters were used 40 times. The detainment rate of the first time
      puncture and the incidence of needle accidents with Jelco plus and Insyte
      autoguard were 98% and 0%, respectively, against 100% and 0%, respectively, for
      all other catheters. There was no difference in the incidence of these two events
      in all groups (ANOVA; p > 0.05). On the other hand, all intravenous catheters
      with safety covers revealed that 1) an in situ needle has a resistance to the
      catheter (i.e., a resistance during catheter release), and/or 2) blood exposure
      can not be sufficiently avoided.

PMID- 15570930
TI  - [Infection control in neutropenia induced by high-dose cytarabine chemotherapy].
AB  - A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully
      used as a postremission consolidation therapy for acute myeloid leukemia (AML).
      Although this chemotherapy has been estimated to cause severe myelosuppression,
      there has been no report about infection risk relating to HDAC chemotherapy. The
      purpose of this retrospective study is to evaluate the infection risk in AML
      patients treated with HDAC (n = 18) compared to those treated with standard-dose
      Ara-C (SDAC, n = 18). The mean duration of severe neutropenia (neutrophils <
      500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively,
      indicating a significant prolongation in the HDAC group (p < 0.05). The frequency
      of febrile neutropenia in the HDAC group tended to increase compared to that in
      the SDAC group (p = 0.093). The average days of usage of quinolone antimicrobial
      prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the
      HDAC group were significantly longer than those of the SDAC group (quinolone; p <
      0.01, aminoglycoside; p < 0.05). The frequency of Streptococcus infection
      isolated from pharyngeal mucus in the HDAC group was significantly higher than
      that in the SDAC group (100% versus 75%; p < 0.05). These results suggest that
      HDAC chemotherapy increased the infection risk compared to SDAC, and especially
      patients who received HDAC need a further prevention plan against gram-positive
      bacteria.

PMID- 15570931
TI  - [Clinical availability of the herbal medicine, SYOUSAIKOTOU, as a gargling agent
      for prevention and treatment of chemotherapy-induced stomatitis].
AB  - The stomatitis accompanying chemotherapy reduces a patient's QOL. Many reports
      have suggested that some kinds of gargling agents for oral mucositis shorten the
      duration and severity of symptoms. This study tested the prevention and efficacy
      against stomatitis of a herbal medicine (Syousaikotou) as a gargling agent for
      patients receiving chemotherapy. Compared to gargling with providone-iodine and
      amphotericin B, the Syousaikotou gargle showed a significantly decreased
      incidence of stomatitis, and a painkilling effect. Stomatitis occurred in about
      17.4% among 23 chemotherapy cycles with the Syousaikotou gargle, against about
      40.8% among 71 chemotherapy cycles without the Syousaikotou gargle. Among the
      patients suffering stomatitis pain after 22 chemotherapy cycles, the painkilling
      effect was seen to be 76.2%, and continues for about 2 hours. Critical side
      effects were not seen, but in 4 cases there were complaints about foul smells,
      such as oil and grass smells. Syousaikotou gargle was considered to be one of the
      useful methods against the stomatitis prevention and sharp pain mitigation from
      the chemotherapy.

PMID- 15570932
TI  - [A case of gastric cancer with paraaortic lymph node metastasis responding to TS
      1/CDDP combination therapy].
AB  - A 53-year-old man had consulted another physician regarding his epigastralgia and
      anorexia. Since gastric cancer was detected, he was referred to our department.
      An upper gastrointestinal endoscopy revealed a type-2 gastric cancer at the upper
      portion of the lesser curvature of the stomach, and an abdominal CT scan showed
      marked swelling of periaortic lymph nodes. Since a radical resection appeared
      impossible, we used preoperative chemotherapy with a combination of TS-1 and
      CDDP. The patient was administered TS-1 for 3 weeks at 120 mg/ day, received an
      intravenous drip infusion of 90 mg/body of CDDP on day 8, and then discontinued
      chemotherapy for 2 weeks, which was regarded as one course. After 2 courses of
      the chemotherapy, an upper gastrointestinal endoscopy showed that the primary
      tumor was reduced in size, the periphery of the tumor almost flattened, and an
      abdominal CT scan confirmed the loss of swelling in the periaortic lymph nodes.
      The responsive rate was evaluated as PR. Since a radical resection was considered
      possible, we performed a total gastrectomy with complete D3 extirpation combined
      with a splenectomy. Histological efficacy was evaluated as grade 2 in primary
      cancer, and grade 3 in lymph nodes. Regrettably, the patient died one year and 7
      months postoperatively. However, we consider the TS-1 and CDDP in combination
      useful as preoperative chemotherapy for advanced gastric cancer with periaortic
      lymph node involvement.

PMID- 15570933
TI  - [A case of recurrent gastric cancer with malignant ascites responding
      dramatically to chemotherapy with paclitaxel infused systemically and
      intraperitoneally].
AB  - We report a case in which chemotherapy with paclitaxel (TXL) infused systemically
      and intraperitoneally was effective for gastric cancer with malignant ascites. A
      69-year-old man suffering from advanced gastric cancer with peritoneal
      dissemination underwent distal gastrectomy, a radical C operation. After
      chemotherapy with TS-1 and low-dose CDDP, TS-1 was administrated on an outpatient
      basis for 6 months. However, he complained of abdominal fullness and ascites, and
      received combination chemotherapy with paclitaxel infused systemically and
      intraperitoneally as second-line treatment. The ascites completely disappeared 5
      weeks after administration. The only toxic event was anemia (grade 1), and no
      major adverse effects were observed.

PMID- 15570934
TI  - [Measurement of docetaxel concentration in blood and ascites after drip infusion
      into each vessel and intraperitoneal cavity of gastric cancer].
AB  - We measured docetaxel (TXT) concentrations in the blood and ascites after drip
      infusion into each vessel and intraperitoneal cavity of a patient with advanced
      gastric cancer. The peak concentration was reached immediately (first time 244
      ng/ml, second time 215 ng/ml) after the infusion of TXT (25 mg/m2) into the
      vessels. The concentration of TXT for ascites peaked after 30 min of drip
      infusion (first time 26 ng/ml, second time 30 ng/ml). AUC ascites/AUC blood was
      27.2% and 35.8% respectively. This is the first report demonstrating the
      concentration of TXT in ascites after drip infusion into vessels. When TXT was
      administered into the peritoneal cavity, the peak concentration of ascites was
      reached immediately (54,200 ng/ml). After 240 min, the TXT concentration in the
      peritoneal cavity was still high (14,200 ng/ml). In blood, the level peaked (64
      ng/ml) at 120 min. After 240 min, the TXT level in the blood remained 44 ng/ml.
      AUC blood/AUC ascites was only 0.25%. These results suggested that the transition
      rate of TXT from blood to intraperitoneal cavity was excellent, and that TXT was
      suitable for the treatment of peritoneal dissemination of gastric cancer.
      Furthermore, infusion of TXT (25 mg/m2) into the peritoneal cavity may directly
      and systemically provide its antitumor effect. If we prefer the antitumor effect
      directly, a much lower dose infusion of TXT may be recommended.

PMID- 15570935
TI  - [A case of liver metastatic recurrence of gastric cancer effectively treated by
      combined chemotherapy of CPT-11 and CDDP].
AB  - The patient was a 72-year-old female with gastric carcinoma. A liver metastatic
      recurrence was detected 27 months after operation. Although temporary partial
      responses were obtained by each effective chemotherapy, which was a combination
      chemotherapy with 5'-DFUR and TXT, TS-1 and TXL, the metastatic lesion proved
      refractory to all of them. Then we tried combination chemotherapy consisting of
      CDDP 30 mg/m2 and CPT-11 60 mg/m2, respectively (day 1 and 15, every 4 weeks). A
      partial response was achieved and continued for 8.5 months, and her complaints
      abated and quality of life improved. Although gastro-intestinal symptoms and bone
      marrow suppression were observed as side effects, they were within a tolerable
      range and did not interfere with the combination therapy. This regimen appears to
      be feasible and effective for recurrent gastric carcinoma refractory to other
      regimens.

PMID- 15570936
TI  - [A case of advanced gastric cancer with multiple liver metastases successfully
      treated with TS-1 and CDDP].
AB  - A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully
      Treated with TS-1 and CDDP: Akihiro Tsukahara, Kazuhiro Kaneko and Syuji Tanaka
      (Dept. of Surgery, Niigata Prefectural Koide Hospital) Summary A 70-year-old
      advanced gastric cancer patient with liver and lymph node metastases was treated
      by chemotherapy with TS-1 and CDDP. One course consisted of administration of TS
      1 100 mg/body for 21 days followed by 14 days rest and infusion of CDDP 80
      mg/body on day 8. At the end of 2 courses, the primary tumor showed a
      hypertrophic wall, but a partial response of the liver metastases (reduction
      ratio was 78.3%) and a complete response of the LN metastasis were achieved. PR
      and CR were maintained after 4 courses. There were no remarkable side effects for
      4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced
      gastric cancer with liver and lymph node metastases.

PMID- 15570937
TI  - [Weekly paclitaxel therapy is useful for gastric carcinoma as second-line
      chemotherapy].
AB  - The patient was a 58-year-old man who suffered from non-resectable gastric
      cancer, staged intraoperatively for peritoneal dissemination and paraaorta lymph
      node metastasis at another hospital in December 2002. He was initially treated
      with TS-1 as an outpatient. However, he was readmitted on March 4, 2003 for
      hematuria, general fatigue, jaundice and dyspnea. He was diagnosed with gastric
      cancer duodenum invasion, obstructive jaundice and lymphangitis carcinomatosa,
      and began weekly TXL as second-line chemotherapy on March 26. TXL (70 mg/ m2) was
      infused once a week for 3 weeks followed by a 1-week interval as one cycle. One
      week after the first infusion therapy, the jaundice and dyspnea were greatly
      improved. CT scan showed the lymphangitis carcinomatosa had disappeared and
      paraaorta lymph node metastasis was reduced to 60% after one cycle of the
      treatment. The toxic events were leukopenia (grade 1) and alopecia (grade 1).

PMID- 15570938
TI  - [A case of advanced colon cancer responding completely to systemic 5
      fluorouracil/l-leucovorin therapy].
AB  - A 79-year-old man was admitted for advanced transverse colon cancer with large
      bowel obstruction. Twelve years earlier he underwent a total gastrectomy with
      Roux-en Y reconstruction for gastric cancer. No metastasis was detected
      preoperatively. Exploratory laparotomy revealed massive direct invasion of the
      mesenterium of the jejunum for Roux-en Y reconstruction. The primary lesion was
      unresected and transverse colostomy was made. Systemic chemotherapy with 5
      fluorouracil and l-leucovorin was scheduled for a total of 4 courses
      postoperatively. After completion of this chemotherapeutic regimen, a CT scan and
      colonofiberscopy revealed the primary lesions had disappeared, and a histological
      examination of biopsy confirmed that the patient had achieved a complete
      remission (CR). There was no severe side effect during chemotherapy. The patient
      is presently enjoying a good general condition and has been free from any sign of
      recurrence.

PMID- 15570939
TI  - [Anastrozole-resistant breast cancer responsive to exemestane--a case report].
AB  - We describe a postmenopausal woman suffering from advanced breast cancer with
      pleural effusion. She had prior anastrozole therapy, and was referred to our
      hospital with dyspnea. The use of exemestane, a highly selective steroidal
      aromatase inhibitor (25 mg daily), successfully induced remission of pleural
      effusion. Exemestane is a useful treatment for postmenopausal woman with advanced
      breast cancer, which is refractory to anastrozole.

PMID- 15570940
TI  - Successful management of a patient with stage IIIA non-small cell lung cancer
      using sensitivity-based induction chemotherapy--report of a case.
AB  - To select the most appropriate drug treatment for different patients with lung
      cancer, we have been measuring the chemosensitivity of lung cancer tissues to
      various drugs using the collagen gel droplet embedded culture drug sensitivity
      test (CD-DST). A 57-year-old Japanese male with stage IIA squamous cell carcinoma
      of the lung received sensitivity-based induction chemotherapy consisting of
      docetaxel (70 mg/m2) given on days 1, 22, and 43. He was treated as an
      outpatient, and no serious side effects were observed. After the chemotherapy,
      the left upper bronchus was reopened by the reduction of the tumor, and a left
      pneumonectomy with simultaneous partial resection of the pericardium was
      performed. After discharge, the patient received 2 cycles of adjuvant
      chemotherapy, consisting of weekly docetaxel doses (35 mg/m2) for 3 consecutive
      weeks, followed by one week without treatment. Although the 3-year survival rate
      of stage IIIA NSCLC patients is under 30%, three years after administration of
      the chemotherapy no other recurrence site has been detected, and the patient is
      in good health. Using CD-DST, sensitivity-based induction chemotherapy with
      docetaxel was successful in the patient reported here.

PMID- 15570941
TI  - [A case of non-small cell lung carcinoma successfully treated with carboplatin
      and weekly paclitaxel under renal dysfunction].
AB  - A 73-year-old man was admitted to our hospital with productive cough and dyspnea.
      His chest X-ray and CT scan showed a mass lesion on the lower lung field, pleural
      effusion on the left side, metastatic lesion in the right lung, and multiple
      metastases in the liver. The diagnosis was non-small cell carcinoma of the lung.
      Unfortunately, he had suffered from chronic nephritis; his creatinine level was
      2.1, and his creatinine clearance was 29 ml/min. He received 4 courses of
      combined chemotherapy of carboplatin (AUC 5, day 1) and weekly paclitaxel (60 mg/
      m2, day 1, 8, 15) every 4 weeks. His subjective symptoms as side effects were
      mild except for accidental melena due to colon diverticulum. Almost all lesions
      identified at admission were regressed by the chemotherapy. Although renal
      dysfunction often prevents patients with lung cancer from receiving systemic
      chemotherapies, in this case the combined chemotherapy of carboplatin and weekly
      paclitaxel proved to be a relatively safe and effective therapy for those
      patients with renal dysfunction.

PMID- 15570942
TI  - [A case of retroperitoneal neuroblastoma in an adult with extensive bone marrow
      metastasis].
AB  - We present a case of retroperitoneal neuroblastoma in a 27-year-old male with
      extensive bone marrow metastasis at the first presentation. After the simple
      excision of the tumor, adjuvant multi-drug chemotherapy, consisting of
      vincristine, actinomycin-D, ifosfamide, doxorubicin, carboplatin and etoposide,
      was carried out for 17 months, leading to complete remission. Ten months after
      completion of the chemotherapy, the tumor recurred with bone marrow metastasis.
      He further developed thoracic vertebral metastases resulting in paraplegia, and
      died of the disease 41 months after the presentation. The clinical course of this
      case, with its emphases especially on the effect of the chemotherapy, is
      described in this report. Since the clinical characteristics and treatment
      strategies for adult neuroblastoma have not yet been well established, they
      remain to be investigated in detail.

PMID- 15570943
TI  - [Renal cell carcinoma].
AB  - It is generally accepted that renal cell carcinoma (RCC) usually metastasizes to
      distant organs through blood circulation rather than lymphatogeneous
      dissemination. Clinical and autopsy studies have revealed that most lymph node
      (LN) metastases accompany distant metastasis. In addition, LN dissection (LND)
      can reveal a positive node in limited cases in which nodes negative
      preoperatively, suggesting that diagnostic significance of LND is low in such
      cases. Although the significance of LND in RCC remains controversial, it is also
      reported that RCC patients with regional LN metastasis alone had an improved
      survival after LND. Animal models have indicated that detection of sentinel nodes
      in RCC might facilitate a more personalized treatment of LND in RCC.

PMID- 15570944
TI  - [Tumor markers in breast cancer].
AB  - A number of breast cancer-orientated tumor markers have been utilized for various
      purposes in clinical practice in Japan. Their purposes are as follows: early
      detection of primary tumors, prediction of disease extent and prognosis, early
      detection of recurrent diseases, evaluation of therapeutic responses, monitoring
      patient outcome, and differential diagnosis of metastatic tumors of unknown
      origin. The clinical significance of the measurement of tumor markers for these
      purposes is overviewed in this article. In addition, the results are summarized
      for two clinical studies conducted by the Tumor Marker Study Group of Japanese
      Breast Cancer Society (Chairperson: Dr. Kurebayashi), a questionnaire survey on
      the current status of tumor markers in breast cancer in Japan and a multi
      institutional study on the utility of tumor markers for evaluation of therapeutic
      responses. Future directions of clinical and experimental research for breast
      cancer-orientated tumor markers are also discussed.

PMID- 15570945
TI  - Scanning probe microscopy in catalysis.
AB  - This review discusses the recent progress in the application of scanning probe
      microscopy (SPM) in catalysis. SPM proves to be an invaluable technique for
      imaging catalytic surfaces and interfaces. Most SPM research is related to the
      structural and morphological transformation associated with catalyst preparation
      and use. Real-time SPM observation of surface dynamics including adsorption,
      diffusion and reaction, provides invaluable insights to the mechanism of
      catalysis. SPM is also used to shape and manipulate surfaces and surface
      processes. Fabrication of nanostructured catalysts, direct manipulation of
      adsorbed atoms and molecules and tip-mediated reactions are some examples of new
      SPM approach in catalyst research.

PMID- 15570946
TI  - Employing Raman spectroscopy to qualitatively evaluate the purity of carbon
      single-wall nanotube materials.
AB  - Carbon single-wall nanotubes (SWNTs) have highly unique electronic, mechanical
      and adsorption properties, making them interesting for a variety of applications.
      Raman spectroscopy has been demonstrated to be one of the most important methods
      for characterizing SWNTs. For example, Raman spectroscopy may be employed to
      differentiate between metallic and semi-conducting nanotubes, and may also be
      employed to determine SWNT diameters and even the nanotube chirality. Single-wall
      carbon nanotubes are generated in a variety of ways, including arc-discharge,
      laser vaporization and various chemical vapor deposition (CVD) techniques. In all
      of these methods, a metal catalyst must be employed to observe SWNT formation.
      Also, all of the current synthesis techniques generate various non-nanotube
      carbon impurities, including amorphous carbon, fullerenes, multi-wall nanotubes
      (MWNTs) and nano-crystalline graphite, as well as larger micro-sized particles of
      graphite. For any of the potential nanotube applications to be realized, it is,
      therefore, necessary that purification techniques resulting in the recovery of
      predominantly SWNTs at high-yields be developed. It is, of course, equally
      important that a method for determining nanotube wt.% purity levels be developed
      and standardized. Moreover, a rapid method for qualitatively measuring nanotube
      purity could facilitate many laboratory research efforts. This review article
      discusses the application of Raman spectroscopy to rapidly determine if large
      quantities of carbon impurities are present in nanotube materials. Raman spectra
      of crude SWNT materials reveal tangential bands between 1500-1600 cm(-1), as well
      as a broad band at approximately 1350 cm(-1), attributed to a convolution of the
      disorder-induced band (D-band) of carbon impurities and the D-band of the SWNTs
      themselves. Since the full-width-at-half-maximum (FWHM) intensity of the various
      carbon impurity D-bands is generally much broader than that of the nanotube D
      band, an indication of the SWNT purity level may be obtained by simply examining
      the line-width of the D-band. We also briefly discuss the effect of nanotube
      bundling on SWNT Raman spectra. Finally, sections on employing Raman
      spectroscopy, and Raman spectroscopy coupled with additional techniques, to
      identify the separation and possible isolation of a specific nanotube within
      purified SWNT materials is provided. Every SWNT can be considered to be a unique
      molecule, with different physical properties, depending on its (n, m) indices.
      The production of phase-pure (n, m) SWNTs may be essential for some nanotube
      applications.

PMID- 15570947
TI  - FePt-Ag nanocomposite thin films with longitudinal magnetic anisotropy.
AB  - A well-controlled method to fabricate FePt thin films with the (200) texture and
      longitudinal magnetic anisotropy for high-density magnetic recording media is
      reported. FePt-Ag nanocomposite thin films with L1(0) ordered FePt grains
      embedded in an Ag matrix were deposited on the Cr90Ru10/glass by co-sputtering
      from Ag and FePt targets. The Ag doping suppressed the (001) texture but improved
      the L1(0) FePt (200) texture. The magnetic easy axis of FePt-Ag thin films
      changed from perpendicular to longitudinal in direction. In-plane coercivity of
      the films varied from 0.8 kOe to 6.5 kOe, depending on Ag contents in the films
      and under-layer thickness. The change from the (001) to (200) texture could be
      due to the competition of grain-boundary energy and epitaxial-strain energy.

PMID- 15570948
TI  - Formation of water-soluble iron oxide nanoparticles derived from iron storage
      protein.
AB  - This paper reports novel findings of an investigation of the formation of water
      soluble iron oxide nanoparticles from iron-storage protein ferritin. The strategy
      couples thermal removal of the protein shell on a planar substrate and subsequent
      sonication in aqueous solution under controlled temperature. Advantages of using
      ferritin as a precursor include well-defined core size, core composition, water
      solubility and processibility. The formation of the nanoparticles was
      characterized using TEM, UV-Vis and FTIR techniques. Iron oxide nanoparticles in
      the size range of 5-20 nm diameters were produced. In addition to thermal
      treatment conditions, the sonication temperature of the nanoparticles in water
      was found to play an important role in determining the resulting particle size.
      This simple and effective route has important implications to the design of
      composite nanoparticles for potential magnetic, catalytic, biomedical sensing and
      other nanotechnological applications.

PMID- 15570949
TI  - Carbon nanotubes grafted on silicon oxide nanowires.
AB  - In this article, we report the grafting of multi-walled carbon nanotubes on
      silica nanowires by directly growing nanotubes on the surfaces of the nanowires
      via chemical vapor deposition (CVD) using ferrocene and xylene as Fe catalyst
      precursor and carbon source, respectively. The grafted carbon nanotubes are a few
      micrometers long with diameters of 10 to approximately 30 nm, and grow uniformly
      along the lengths of the nanowires. The distribution density of the grafted
      carbon nanotubes on the silica nanowires can be tuned by simply adjusting the CVD
      growth temperature. Our method provides a simple approach for synthesizing
      nanometer scale grafted heterostructures between nanotubes and nanowires, which
      could be used to design and construct high-performance filters, chemical sensors
      and reinforced composites.

PMID- 15570950
TI  - Carbon nanotubes and other fullerene nanocrystals in domestic propane and natural
      gas combustion streams.
AB  - Carbon nanotubes and other aggregated fullerene-related multi-layer shell
      structures have been collected in propane and natural gas flame emissions from
      domestic cooking stoves and observed by transmission electron microscopy. Some
      aggregated nanoparticles collected on 3 mm electron microscope grids by thermal
      precipitation were mostly multi-walled nanotubes; many tangled and distorted, and
      aggregated with other closed-concentric, multi-shell forms. Such clean-burning
      regimes may be major contributors to complex particulate matter in indoor and
      outdoor air.

PMID- 15570951
TI  - Synthesis of bamboo-shaped carbon-nitrogen nanotubes using acetonitrile-ferrocene
      precursor.
AB  - We report the formation of bamboo-shaped carbon-nitrogen nanotubes by employing a
      simple, one-step and economically viable spray pyrolysis technique using new
      precursor; acetonitrile and ferrocene solution. By varying the concentration of
      ferrocene with respect to acetonitrile, it has been found that the optimum
      concentration of ferrocene in acetonitrile is 5 mg/ml. The special feature of the
      as-synthesized bamboo-shaped carbon-nitrogen nanotubes bundles is that they are
      produced in a high yield (1.25 gms/run). They also have long linear extents
      (approximately 430 microm) and are very clean. The average composition of carbon
      nitrogen nanotubes comes out to be C26N.

PMID- 15570952
TI  - Magnetism and magnetotransport in sonochemically-prepared amorphous Co(100
      x)Pt(x) nanoalloys.
AB  - Amorphous nanoalloys of Co(100-x)Pt(x) (0 < or = x < or = 50) prepared
      sonochemically exhibit a negative magnetotransport effect, showing a maximum for
      platinum volume fraction of 10%. The oscillatory peak maxima observed in x = 30
      composition for residual resistivity, rho0 and Tmin corresponds to the peak
      minima for the negative MR% in the range of compositions studied. We observe that
      in weakly exchange coupled amorphous alloys, the local magnetic order at Tmin and
      the disorder effects observed from rho0 become crucial.

PMID- 15570953
TI  - Novel methods of forming self-assembled nanostructured materials: Ni nanodots in
      Al2O3 and TiN matrices.
AB  - We have developed two novel methods of growing self-assembled nanodot arrays of
      uniform size (diameter 2-50 nm) of a variety of materials in crystalline as well
      as amorphous matrices. These methods employ a pulsed laser deposition technique
      and are classified as: (a) sequential growth method; and (b) simultaneous growth
      method. In the first method, the nanodots and matrix material are formed
      sequentially, while in the second method, nanodots and matrix materials grow
      simultaneously. In the sequential growth, self-assembly of nanodots is controlled
      by the flux of materials, interfacial energy, intervening matrix layer, substrate
      and laser parameters. For the simultaneous growth method of self-assembly of
      nanodots, there is additional requirement that the material of the nanodot and
      the matrix should be such that the Gibb's free energy of oxidation of the
      constituent of matrix material is much lower than that of the nanodot material.

PMID- 15570954
TI  - A titania nanotube-array room-temperature sensor for selective detection of
      hydrogen at low concentrations.
AB  - A tremendous variation in electrical resistance, from the semiconductor to
      metallic range, has been observed in titania nanotube arrays at room temperature,
      approximately 25 degrees C, in the presence of < or = 1000 ppm hydrogen gas. The
      nanotube arrays are fabricated by anodizing titanium foil in an aqueous
      electrolyte solution containing hydrofluoric acid and acetic acid. Subsequently,
      the arrays are coated with a 10 nm layer of palladium by evaporation. Electrical
      contacts are made by sputtering a 2 mm diameter platinum disk atop the Pd-coated
      nanotube array. These sensors exhibit a resistance variation of the order of
      10(4) in the presence of 100 ppm hydrogen at 25 degrees C. The sensors
      demonstrate complete reversibility, repeatability, high selectivity, negligible
      drift and wide dynamic range. The nanoscale geometry of the nanotubes, in
      particular the points of tube-to-tube contact, is believed to be responsible for
      the outstanding hydrogen gas sensitivities.

PMID- 15570955
TI  - Synthesis and characterization of extremely uniform Fe-Co-Ni ternary alloy
      nanowire arrays.
AB  - We have fabricated extremely uniform arrays of polycrystalline Fe-Co-Ni ternary
      alloy nanowires having composition Fe 12.3 wt.%, Co 43.9 wt.% and Ni 43.8 wt.%.
      The wires are made by electrodeposition into nanoporous alumina templates, using
      an electrodeposition voltage of 15 V at 1000 Hz. Nanowires have been fabricated
      having diameters ranging from 43 nm to 120 nm, and lengths of 3 microm to 7
      microm, as dependent upon template topology. The magnetization easy axis lies
      along the nanowire length, with an easy axis coercivity of 72 kA/m.

PMID- 15570956
TI  - Temperature effects on resistance of aligned multiwalled carbon nanotube films.
AB  - Electrical transport in vertically aligned films of multiwalled carbon nanotubes
      has been investigated in the -150 degrees C to 300 degrees C temperature range
      (all the tests were conducted in air at atmospheric pressure). In all the cases,
      the nanotube film exhibited a semi-conducting behavior, with the film resistance
      decreasing with increasing temperature. Removal of amorphous carbon contamination
      (via plasma etching) significantly improved the nanotube film's sensitivity to
      temperature changes (particularly in the 20 degrees C to 200 degrees C
      temperature range). All the of films tested in this study showed a consistent,
      repeatable behavior that was independent of the nanotube film length. The
      temperature sensitivity of the nanotube films was also found to be independent of
      the heating/cooling rates and without hysteresis. Because of the excellent
      repeatability and stability of the results, it is conceived that miniaturized
      temperature sensors could be designed using such aligned multiwalled nanotube
      films.

PMID- 15570957
TI  - Analysing one isolated single walled carbon nanotube in the near-field domain
      with selective nanovolume Raman spectroscopy.
AB  - In this paper, we describe a new method to the selective nanovolume analysing of
      one isolated single walled carbon nanotube (SWNT). This concept is based on
      actually available imaging micro-spectrometry systems for working in near-field
      domain combined with a stigmatic solid immersion lens. This combination of
      different analytical methods, and modified and configured equipment entitles us
      to expand the functionality toward a three-dimensional (3D) nanovolume Raman
      mapping and photoluminescence intensity with a possible discrimination in
      polarization, as well as photoluminescence decaytime constant mapping with their
      unique combination. Subsequently, selective spectra can be acquired from the same
      location on the samples. By spectrally selecting a SWNT, we registered the
      spatial distribution of the emitted photons in x, y, z vectors to determine the
      position of a SWNT in the near-field domain. For the SWNTs that are localized
      with an accuracy better than 18 nm in the x, y and <1 nm in the z directions, we
      demonstrate an analytical sensitivity close to a single nanotube with unity
      throughput. This near-field capability is applied to resolve local variations
      unambiguously in the Raman spectrum along one single SWNT. Finally, in this
      paper, we report what we believe to be the first evidence of Raman mapping and 3D
      real optical imaging of carbon nanotubes with near-field resolution.

PMID- 15570958
TI  - A parametric study of single-wall carbon nanotube growth by laser ablation.
AB  - Results of a parametric study of carbon nanotube production by the double-pulse
      laser oven process are presented. The effect of various operating parameters on
      the production of single-wall carbon nanotubes (SWCNTs) is estimated by
      characterizing the nanotube material using analytical techniques, including
      scanning electron microscopy, transmission electron microscopy, thermo
      gravimetric analysis and Raman spectroscopy. The study included changing the
      sequence of the laser pulses, laser energy, pulse separation, type of buffer gas
      used, operating pressure, flow rate, inner tube diameter, as well as its
      material, and oven temperature. It was found that the material quality and
      quantity improve with deviation from normal operation parameters such as laser
      energy density higher than 1.5 J/cm2, pressure lower than 67 kPa, and flow rates
      higher than 100 sccm. Use of helium produced mainly small diameter tubes and a
      lower yield. The diameter of SWCNTs decreases with decreasing oven temperature
      and lower flow rates.

PMID- 15570959
TI  - A simple and novel method to synthesize doped and undoped SnO2 nanocrystals at
      room temperature.
AB  - This work describes the synthesis, at room temperature, of doped and undoped SnO2
      nanocrystals (particle size ranging from 1-3 nm) with no thermal or hydrothermal
      treatment. To the best of our knowledge, this is the first time that the
      synthesis, at room temperature, of doped and/or undoped SnO2 nanocrystals has
      been reported. This new synthesis method is based on the controlled oxidation,
      hydrolysis and polycondensation of tin ions in an ethanol solution. Another novel
      aspect of this method is the possibility of using surfactants, which may provide
      improved control over the particle size.

PMID- 15570960
TI  - Hydrocarbon decomposition in alumina membrane: an effective way to produce carbon
      nanotubes bundles.
AB  - Carbon nanotubes were synthesised within the pores of an alumina membrane. The
      membrane had 200 nm diameter pores and 60 microm thickness, and ethylene was used
      as carbon source. Membrane dissolution by HF results in a bundle of parallel open
      tubes, aligned without macroscopic defects. The external diameter of the tubes is
      uniform and there is no evidence of any amorphous carbon. Wall thickness control
      was obtained by varying the reaction time, length by the thickness of alumina
      membrane, and external tube diameter by the membrane pore size. Scanning (SEM)
      and transmission (TEM) electron microscopy, atomic force microscopy (AFM), X-ray
      diffraction, thermogravimetric analysis (TG) and surface area evaluation by
      nitrogen adsorption were used for the characterization of membrane and nanotubes.

PMID- 15570961
TI  - Synthesis of palladium nanoparticles using a continuous flow polymeric micro
      reactor.
AB  - A continuous flow polymeric micro reactor, fabricated using a negative photo
      resist SU-8 on a 10 x 10 cm PEEK (polyetheretherketone) substrate by standard UV
      lithography, was utilized to synthesize palladium nanoparticles. The
      nanoparticles were characterized by Transmission Electron Microscopy, Selected
      Area Electron Diffraction and X-ray Diffraction. The Pd nanoparticles synthesized
      in the micro reactor were found to have a narrower size distribution when
      compared with those obtained by the conventional batch process.

PMID- 15570962
TI  - Graphitic carbon nanofiber (GCNF)/polymer materials. I. GCNF/epoxy monoliths
      using hexanediamine linker molecules.
AB  - Processing methods have been optimized for the formation of graphitic carbon
      nanofiber (GCNF)/epoxy nanocomposites containing GCNFs highly dispersed
      throughout a thermoset epoxy matrix. GCNFs having a herringbone atomic structure
      are surface-derivatized with bifunctional hexanediamine linker molecules (GCNF
      HDA) capable of covalent binding to an epoxy matrix during thermal curing and are
      cut to smaller dimension using high-power ultrasonication. GCNF-HDA nanofibers
      are dispersed in epoxy resin at 0.3 wt.% loading using variable levels of
      ultrasonication processing prior to thermal curing. Effects of sonication power
      on the quality of the GCNF-HDA/epoxy material obtained after curing have been
      determined from flexural property measurements, thermomechanical analysis and
      SEM/TEM imaging. GCNF-HDA/epoxy material of the highest quality is obtained using
      low-power sonication, although high-power sonication for short periods gives
      improved flexural properties without lowering the glass transition temperature.
      Good dispersion and polymer wetting of the GCNF component is evident on the
      nanoscale.

PMID- 15570963
TI  - Carbothermal transformation of a graphitic carbon nanofiber/silica aerogel
      composite to a SiC/silica nanocomposite.
AB  - Carbon nanofiber/silica aerogel composites are prepared by sol-gel processing of
      surface-enhanced herringbone graphitic carbon nanofibers (GCNF) and Si(OMe)4,
      followed by supercritical CO2 drying. Heating the resulting GCNF/silica aerogel
      composites to 1650 degrees C under a partial pressure of Ar gas initiates
      carbothermal reaction between the silica aerogel matrix and the carbon nanofiber
      component to form SiC/silica nanocomposites. The SiC phase is present as nearly
      spherical nanoparticles, having an average diameter of ca. 8 nm. Formation of SiC
      is confirmed by powder XRD and by Raman spectroscopy.

PMID- 15570964
TI  - Preparation of Pt-Re/Vulcan carbon nanocomposites using a single-source molecular
      precursor and relative performance as a direct methanol fuel cell
      electrooxidation catalyst.
AB  - Pt-Re/Vulcan carbon powder nanocomposites have been prepared with total metal
      loadings of 18 wt.% and 40 wt.% using a new non-cluster (1:1)-PtRe bimetallic
      precursor as the source of metal. Pt-Re nanoparticles having an average diameter
      of ca. 6 nm and atomic stoichiometry near 1:1 are formed. TEM, on-particle HR
      EDS, and powder XRD data are consistent with the formation of Pt-Re alloy
      nanoparticles having a hexagonal unit cell with cell constants of a = 2.77 A and
      c = 4.47 A. A nanocomposite prepared at higher total metal loading under more
      rigorous thermal treatment also contains Pt-Re alloy nanoparticles having a fcc
      unit cell structure (a = 3.95 A). The precise dependence of Pt-Re nanocrystal
      structure on the thermal history of the nanocomposite specimen has not been
      investigated in detail. While these Pt-Re/carbon nanocomposites are active as
      anode catalysts in operating direct methanol fuel cells, the measured performance
      is less than that of commercial Pt-Ru/carbon catalysts and has marginal practical
      importance.

PMID- 15570965
TI  - New hetero silicon-carbon nanostructure formation mechanism.
AB  - We report the formation of silicon and carbon hetero-nanostructures in an
      inductively coupled plasma system by a simultaneous growth/etching mechanism.
      Multi-walled carbon nanotubes were grown during one, three and five hour
      depositions, while tapered silicon nanowires were progressively etched. The
      carbon and silicon nanostructures and the interfaces between them were studied by
      electron microscopies and micro Raman spectroscopies. The potential of this
      method for large-scale controlled production of nano heterostructures without the
      requirement of a common catalyst is explored.

PMID- 15570966
TI  - A simple route towards CuO nanowires and nanorods.
AB  - CuO nanowires and nanorods were synthesized through a novel controllable solution
      phase hydrothermal method using a nonionic surfactant polyethylene glycol (PEG)
      as the structure-directing template. The lengths of obtained 1D CuO
      nanostructures could be successfully controlled through choosing different
      molecular weights of PEG. The phase structures and morphologies were investigated
      by XRD, TEM, HRTEM and SAED. The formation mechanisms of the nanorods and
      nanowires were investigated and discussed on the basis of the experimental
      results.

PMID- 15570967
TI  - Shape and size control of ZnO nanostructures via a simple solution route.
AB  - ZnO nanostructures with different morphologies were synthesized by condensing the
      Zn(OH)4(2-) precursors under hydrothermal conditions in the presence of a
      surfactant, cetyltrimethylammonium bromide (CTAB). Shape and size control of ZnO
      nanostructures was achieved by relatively simple variations of molar ratio of
      CTAB to Zn(OH)4(2-). With a higher molar ratio, ZnO nanotubes were obtained,
      whereas with a lower molar ratio, ZnO nanorods were formed; furthermore, with a
      moderate w value, the coexistence of ZnO nanorods and nanotubes was also
      observed. The photoluminescence of ZnO nanorods and nanotubes was also
      investigated.

PMID- 15570968
TI  - Surfactant-assisted synthesis of Keggin-type polyoxometalates nanorods.
AB  - It was demonstrated that Keggin-type polyoxometalates nanorods (POMs-nanorods)
      were prepared from a solution containing a surfactant polyethylene glycol (PEG),
      when heteropolyanions [X(n+)M12O40](-(8-n)) (X(n+) = P5+ and Si4+; M = W and Mo)
      were precipitated by ammonia ion obtained by hydrolysis of urea at 373 K. In this
      method, PEG was used as a template and ammonia ion (NH4+) was a counterion. In an
      oil bath kept at 373 K without stirring, three kinds of ammonium salts of POMs,
      i.e., (NH4)3PW12O40, (NH4)4SiW12O40, and (NH4)3PMo12O40 nanorods were obtained.
      The POMs-nanorods were characterized by transmission electron microscopy (TEM),
      selected area electron diffraction (SAED), infrared spectra (IR), inductively
      coupled plasma atomic emission spectrometry (ICP-AES) and X-ray powder
      diffraction (XRD). TEM showed that nanorods were 0.5-1.5 microm in length, and 50
      150 nm in diameter. The results of IR, ICP-AES and XRD proved the existence of
      Keggin structure. The formation process of POMs-nanorods, (NH4)(8-n)
      [X(n+)M12O40](-(8-n)) (X(n+) = P5+ and Si4+; M = W and Mo) in a H2O/PEG system
      was discussed.

PMID- 15570969
TI  - Role of interfacial effects in carbon nanotube/epoxy nanocomposite behavior.
AB  - The interfacial effects are critical to understand the nanocomposite behavior
      based on polymer matrices. These effects are dependent upon the morphology of
      carbon nanotubes, the type of used polymer and the processing technique. Indeed,
      we show that the different parameters, as the eventual surfactant use, the
      ultrasonic treatment and shear mixing have to be carefully examined, in
      particular, for nanotube dispersion and their possible alignment. A series of
      multiwalled nanotubes (MWNT) have been mixed with a regular epoxy resin under a
      controlled way to prepare nanocomposites. The influence of nanotube content is
      examined through helium bulk density, glass transition temperature of the matrix
      and direct current electrical conductivity measurements. These results, including
      the value of the percolation threshold, are analyzed in relationship with the
      mesostructural organization of these nanotubes, which is observed by standard and
      conductive probe atomic force microscopy (AFM) measurements. The wrapping effect
      of the organic matrix along the nanotubes is evidenced and analyzed to get a
      better understanding of the final composite characteristics, in particular, for
      eventually reinforcing the matrix without covalent bonding.

PMID- 15570970
TI  - Synthesis of size-tunable gold nanoparticles by poly(vinylphenol) and
      electrostatic multilayer deposition of the gold-poly(vinylphenol) nanocomposites.
AB  - Water-dispersible gold nanoparticles (GNPs) were synthesized by the polymer in
      situ redox technique at room temperature using poly(4-vinylphenol) (PVPh) as a
      simultaneous template/stabilizer and reducing agent. GNPs were characterized by
      its surface plasmon absorption peak at 536 nm. The average particle size of the
      gold-poly(4-vinylphenol) (Au-PVPh) nanocomposites decreases with increase in the
      ratio of PVPh to gold salt. A uniform multilayer of Au-PVPh nanocomposites was
      fabricated on glass surface by electrostatic layer-by-layer assembly using
      poly(diallyldimethylammonium chloride) (PDDAC) as the oppositely charged
      polycation. UV-vis spectra of the consecutive multilayer showed that the
      absorbance at 549 nm corresponding to GNPs increases linearly with the number of
      Au-PVPh nanocomposite layers, indicating regular bilayer growth.

PMID- 15570971
TI  - Electrical properties of Fe-Fe3O4-SiO2 gel nanocomposites.
AB  - Nanocomposites containing Fe3O4 and alpha-Fe, respectively, in a SiO2 gel were
      prepared by subjecting a suitably chosen gel with iron ions to a reduction
      treatment at 923 K, followed by wet oxidation at the same temperature for 1 hour.
      The particle sizes of the two phases were estimated to have values in the range
      of 18 to 25 nm. The dc conductivity of the composites was found to arise due to a
      variable range hopping mechanism with a density of states calculated as
      approximately 10(18) eV(-1) cc(-1). The nanoparticles of alpha-Fe are believed to
      contribute to the latter. The ac conductivity variation as a function of
      frequency and temperature could be explained because of an overlapping small
      polaron tunneling mechanism in the Fe3O4 nanoparticles. The density of states
      estimated in the latter case was approximately 10(18) eV(-1) cc(-1). From the
      dielectric modulus spectra of the nanocomposites, a Kohlrausch-Williams-Watts
      (KWW) exponent of approximately 0.30 was extracted. This indicated the presence
      of a wide distribution of relaxation times in the system.

PMID- 15570972
TI  - Photoinduced phenomena in layer-by-layer films of poly(allylamine hydrochloride)
      and Brilliant Yellow azodye.
AB  - The nanoscale interactions between adjacent layers of layer-by-layer (LBL) films
      from poly(allylamine hydrochloride) (PAH) and azodye Brilliant Yellow (BY) have
      been investigated, with the films employed for optical storage and the formation
      of surface-relief gratings. Using Fourier transform infrared spectroscopy, we
      identified interactions involving SO3- groups from BY and NH+ groups from PAH.
      These electrostatic interactions were responsible for the slow kinetics of
      writing in the optical storage experiments, due to a tendency to hinder
      photoisomerization and the subsequent reorientation of the azochromophores. The
      photoinduced birefringence did not saturate after one hour of exposure to the
      writing laser, whereas in azopolymer films, saturation is normally reached within
      a few minutes. On the other hand, the presence of such interactions prevented
      thermal relaxation of the chromophores after the writing laser was switched off,
      leading to a very stable written pattern. Moreover, the nanoscale interactions
      promoted mass transport for photoinscription of surface-relief gratings on PAH/BY
      LBL films, with the azochromophores being able to drag the inert PAH chains when
      undergoing the trans-cis-trans photoisomerization cycles. A low level of
      chromophore degradation was involved in the SRG photoinscription, which was
      confirmed with micro-Raman and fluorescence spectroscopies.

PMID- 15570973
TI  - In-situ fabrication of nanostructured cobalt oxide powders by spray pyrolysis
      technique.
AB  - Nano-crystalline Co3O4 and CoO powders have been prepared by a spray pyrolysis
      approach. The effects of the reaction temperature and initial salts on the
      crystallinity and phase composition have been studied. Based on the TEM and XRD
      results, the crystal sizes were in the range of 1-10 nm. SEM and TEM observations
      also reveal that the nano-powders easily create micron-scale spherical
      agglomerates. The Co3O4 powders obtained by spraying nitrate solution at 500
      degrees C show high specific surface area, which according to the BET method is
      82.37 m2/g. The time/temperature phase diagram of cobalt oxides developed from
      XRD and DTA/TGA analyses shows the existence of a CoO phase at low and high
      temperature ranges when some specific preparation conditions are applied.

PMID- 15570974
TI  - High-resolution and analytical TEM investigation of metastable-tetragonal phase
      stabilization in undoped nanocrystalline zirconia.
AB  - Submicron and nano-sized nanocrystalline pure zirconia (ZrO2) powders having
      metastable tetragonal and tetragonal-plus-monoclinic crystal structures,
      respectively, were synthesized using the sol-gel technique. The as-precipitated
      and the calcinated ZrO2 powders were analyzed for their morphology,
      nanocrystallite size and structures, aggregation tendency, local electronic
      properties, and elemental compositions by conventional and high-resolution
      transmission electron microscopy and field-emission analytical electron
      microscopy, including energy-dispersive X-ray and electron energy-loss
      spectroscopies. The results from this study indicate that a combination of
      nanocrystallite size, strain-induced grain-growth confinement, and the
      simultaneous presence of the monoclinic phase can lead to stabilization of the
      metastable tetragonal-phase in undoped ZrO2. As a result, the tetragonal phase is
      stabilized within ZrO2 nanocrystallites up to 100 nm in size, which is 16 times
      larger than the previously reported critical size of 6 nm.

PMID- 15570975
TI  - Cationic silica nanoparticles as gene carriers: synthesis, characterization and
      transfection efficiency in vitro and in vivo.
AB  - The potential of cationic SiO2 nanoparticles was investigated for in vivo gene
      transfer in this study. Cationic SiO2 nanoparticles with surface modification
      were generated using amino-hexyl-amino-propyltri-methoxysilane (AHAPS). The zeta
      potential of the nanoparticles at pH = 7.4 varied from -31.4 mV (unmodified
      particles; 10 nm) to +9.6 mV (modified by AHAPS). Complete immobilization of DNA
      at the nanoparticle surface was achieved at a particle ratio of 80 (w/w
      nanoparticle/DNA ratio). The surface modified nanoparticle had a size of 42 nm
      with a distribution from 10-100 nm. The ability of these particles to transfect
      pCMVbeta reporter gene was tested in Cos-1 cells, and optimum results were
      obtained in the presence of FCS and chloroquine at a particle ratio of 80. These
      nanoparticles were tested for their ability to transfer genes in vivo in the
      mouse lung, and a two-times increase in the expression levels was found with
      silica particles in comparison to EGFP alone. Very low or no cell toxicity was
      observed, suggesting silica nanoparticles as potential alternatives for gene
      transfection.

PMID- 15570976
TI  - Electrochemical assay of nonlabeled DNA chip and SNOM imaging by using
      streptavidin-biotin interaction.
AB  - The assay of DNA biosensor-based nucleic acid recognition using microfabrication
      technology provides for high sensitivity, good surface coverage and
      reproducibility. We have achieved efficient immobilization and hybridization of
      nonlabeled DNA using cyclic voltammetry (CV), square wave voltammetry (SWV) and
      scanning near-field optical microscopy (SNOM) techniques. The increased
      electrochemical response observed following the immobilization of biotinlyated
      ssDNA probe suggests that nucleic acid is a somewhat better medium for electronic
      transfer. We demonstrated the high coverage of immobilized FITC-labeled
      biotinylated DNA probe on a streptavidin-modified surface using SNOM imaging.
      SNOM imaging of FITC-labeled complementary DNA also exhibited fluorescent light
      spots of hybridization distributed throughout. No fluorescent light was observed
      with the hybridization of non-complementary DNA.

PMID- 15570977
TI  - Hydrogen-bonded nanotubes as a model for DNA transcription.
AB  - Using the energy asymmetries in the hydrogen-bonded structures, the model is
      formulated explaining melting of DNA double chain and also explaining further
      decay of only one of the obtained single chains. The model is similar to the
      Scott's model of alpha-helix, where the spiral is substituted with interacting
      discs. The explanation of mentioned DNA transformation is based on the estimate
      of free energy of discs with an even number of hydrogen bonds, and an estimate of
      melting point temperature for the subsystem of odd index fibers and transition
      temperature of the subsystem of even index fibers.

PMID- 15570978
TI  - Influence of the nanoscale support on carbon deposition and carbon elimination
      over Ni/gamma-Al2O3 catalyst for CH4 conversion.
AB  - Characteristics of carbon deposition by CH4 and carbon elimination by CO2 over
      conventional and nanoscale Ni/gamma-Al2O3 catalysts were investigated by using a
      pulse reaction, as well as by TGA, TEM, TPO-MS, H2-TPR and H2-chemisorption
      techniques. It was found that the behaviors of carbon deposition by CH4
      decomposition and carbon elimination by CO2 depend on the active metal dispersion
      and the metal-support interaction. The filamentous carbon was formed on the
      conventional Ni/gamma-Al2O3 catalyst with low metal dispersion and relatively
      large particles, this type of filamentous carbon was far from the active centers
      and difficult to eliminate by CO2. On the other hand, the carbon deposition
      originated from CH4 decomposition on the nanoscale Ni/gamma-Al2O3 catalyst would
      mainly cover the surface of active centers, this type of highly active carbon was
      easily eliminated by CO2 because it is close to the active center Ni atoms. As a
      result, the improvement of coking-resistance was ascribed to the high metal
      dispersion and strong metal-support interaction, a model of CH4 decomposition
      carbon deposition on Ni/gamma-Al2O3 catalyst was proposed.

PMID- 15570979
TI  - A room-temperature synthesis of titanium nitride hollow spheres.
AB  - Titanium nitride hollow spheres were synthesized by the reaction of TiCl4 and
      NaNH2 at room temperature. X-ray powder diffraction (XRD) pattern could be
      indexed as cubic TiN with the lattice constants of a = 4.236 A. Transmission
      electron microscopy (TEM) images showed hollow spheres with diameter about 200
      nm. A possible formation mechanism of TiN hollow spheres was discussed.

PMID- 15570980
TI  - Thermodynamics and phase equilibria involving nano phases in the Cu-Ag system.
AB  - The surface tensions of the Cu-Ag system have been evaluated using Butler's
      equations. Since the evaluation is dependent on the thermodynamic properties of
      the surface phases, they are calculated based on the first and second order
      differentials of the surface tension at infinite dilution. The present study
      establishes significant differences in the properties between the surface phase
      and bulk phases of the system. The study of the adsorption behaviour finds silver
      to be surface active relative to copper, which results in the preferential
      adsorption of silver in the alloys. Furthermore, in view of the differences in
      terms of fundamental thermodynamic properties between the two phases coupled with
      the volume-to-radius ratio as depicted by the Thomson-Freundlich concept, the
      nano phases of the system exhibit a pronounced increase in the adsorption
      behaviour relative to that of the planar interface of the system. As expected
      based on the above combined effect of the surface properties, present research
      shows a considerable decrease in the melting points of the metals, solid-solid,
      solid-liquid transition and eutectic temperature with a consequent increase in
      the solubilities of the terminal phases of the system.

PMID- 15570981
TI  - Clustering effects on discontinuous gold film NanoCells.
AB  - Reproducible negative differential resistance (NDR)-like switching behavior is
      observed in NanoCells. This behavior is attributed to the formation of filaments
      and clusters between the discontinuous gold films. Control experiments are
      performed by self-assembly of insulating molecules between the gold islands and
      conducting molecules on these islands. Additional control experiments are
      performed by removing the filaments and clusters between islands using a piranha
      bath. The results are consistent with theoretical predictions and extend the
      domain of molecular electronics based in organic molecules to include nanosized
      clusters as active units. This facilitates a scenario where synthetically
      accessible organic molecules, with defined characteristics, can be adjusted by
      metallic nanoclusters as an in situ fine-tuning element, able to compensate for
      the lack of addressing in the nanosize regime.

PMID- 15570982
TI  - Hermaphroditus in Greco-Roman myth: lessons and hypotheses for intersex today.
AB  - This discussion reviews the Greco-Roman mythic origins of the eponymic
      Hermaphroditus. It reviews the two major tales, one Greek, the other from Ovid,
      regarding the origins of the sexual and gender predicament of Hermaphroditus. It
      explains the genealogy of Hermaphroditus in Greek mythology, and includes a
      discussion of Ovid's text on Hermaphroditus. A comparison of the two renditions
      offers the opportunity to reflect on who Hermaphroditus may have been, and to
      reflect on the implications of his nature. The discussion also attends to some of
      the ethical and emotional conflicts for the intersexed today. Finally, the
      discussion explores whether lessons from, and hypotheses regarding a mythic
      figure, such as Hermaphroditus, may provide guidance for intersexed individuals
      and their parents.

PMID- 15570983
TI  - The saga of untreated congenital adrenal hyperplasia.

PMID- 15570984
TI  - Abnormalities in blood osmolality after neurosurgery.

PMID- 15570985
TI  - Endocrine function and water metabolism in children and adolescents with
      surgically treated intra/parasellar tumors.
AB  - Hydroelectrolytic disorders often complicate surgery of intra/parasellar tumors
      in children and adolescents. Eighteen patients undergoing microneurosurgical
      procedures for intra-supra-sellar craniopharyngioma (10 patients), hypothalamic
      germinomas (3 patients), hypothalamic-chiasmatic astrocytomas (3 patients),
      pituitary adenomas (2 patients) were studied. The hydroelectrolytic balance was
      assessed from 8 hours before surgery to 1 week after with a specific protocol in
      which water metabolism alterations were treated with standard procedure. Diabetes
      insipidus (DI) was observed in 10/18 patients before surgery and in 15/18
      patients after surgery; during surgery it was effectively treated with synthetic
      desmopressin (DDAVP) and hydroelectrolytic solutions. Hyponatremia, isolated or
      associated (with diuresis contraction or polyuria), seen during surgery and in
      the following 24 hours, was treated with variation of the infusion rate. We show
      that close monitoring and treatment of hydroelectrolytic disorders in patients
      submitted to neurosurgery for intra/ parasellar tumors may significantly reduce
      their morbidity and mortality rate.

PMID- 15570986
TI  - Pubertal development in children born small for gestational age.
AB  - Reduced fetal growth appears to be associated with precocious adrenarche, early
      puberty and polycystic ovary syndrome with subsequent fertility problems. We
      investigated pubertal development and DHEAS levels in children born small for
      gestational age (SGA) and children born appropriate for gestational age (AGA).
      Physical examination was carried out twice. Mean age (+/-SD) at the first visit:
      SGA group, 9.1+/-1.1 yr; AGA group, 9.0+/-1.1 yr. AT FOLLOW-UP: SGA group, 11.6+/
      1.0 yr; AGA group, 11.6 +/-1.1 yr. Pubertal stages of the children were assessed.
      Pubic hair was recorded as a measure of androgenization. Chronological age (CA)
      was expressed as a percentage of the age corresponding to the pubertal stage
      (CA/pubertal age [PA] x 100%). Estradiol, testosterone and dehydroepiandrosterone
      sulfate (DHEAS) were measured in all children. FIRST VISIT: All children were
      prepubertal without signs of pubarche. DHEAS concentrations were higher in SGA
      children than in AGA children (p = 0.004). FOLLOW UP: Twenty SGA children and 15
      AGA children were pubertal. CA/PA x 100% was lower in SGA girls than in AGA girls
      (p = 0.004). Since 2.5 years earlier all girls had been prepubertal, this means a
      more rapid progression in the SGA girls. CA/PA x 100% was similar in SGA and AGA
      boys (p = 0.1). DHEAS levels tended to be higher in SGA children than in AGA
      children (p = 0.06). These data support that a low birth weight may have long
      lasting effects on pubertal development, as observed in a more rapid progression
      in SGA girls. In prepubertal SGA children, an exaggerated adrenarche is observed
      compared to AGA children, which tended to persist through puberty.

PMID- 15570987
TI  - Age at menarche and body mass index: a population study.
AB  - OBJECTIVE: To test the hypothesis that age at menarche is inversely related to
      body mass index (BMI). POPULATION AND METHODS: A questionnaire was filled in by
      11,293 young women at the time of discharge from compulsory military service, in
      order to determine the self-reported age at onset of menarche. The participants
      were weighed and measured and BMI was calculated. Obesity was defined as BMI >30
      and leanness as BMI <20. RESULTS: The age at menarche was significantly and
      inversely correlated with BMI (R = -0.11, p <0.001). The age at menarche of obese
      women (12.9+/-1.3 years) was significantly lower than that of non-obese, non-lean
      women (13.3+/-1.4 years), who themselves had a lower age at menarche than lean
      women (13.5+/-1.4 years) (p <0.001). CONCLUSIONS: We conclude from our data that
      the relationship between BMI and pubertal development in girls appears to be a
      continuum.

PMID- 15570988
TI  - Pamidronate treatment of less severe forms of osteogenesis imperfecta in
      children.
AB  - BACKGROUND: Bisphosphonate therapy improves bone quality in children with severe
      osteogenesis imperfecta (OI). Children with milder phenotypes also have
      prepubertal fractures, bone pain and reduced bone mass, predisposing them to
      adult osteoporosis. OBJECTIVE: To evaluate treatment effects of pamidronate in
      children with mild phenotypes of OI. METHODS: Open label, 2-year observational
      study of 18 patients, using pamidronate, with clinical, biochemical and
      radiological monitoring. RESULTS: Over 2 years, bone pain decreased from 16 to 1
      patient and disturbed sleep from 12 children to 0. Independent mobility improved
      from 10 to 17 children. Fracture incidence decreased from 1.6 to 0.5
      fractures/child/year. Surgical interventions decreased from a mean 1.3
      procedures/patient to 0 in the second year of treatment. Growth velocity remained
      stable at a mean 4.8 cm/year. Mean lumbar vertebral bone mineral density improved
      by 40.8%, from 0.375 to 0.528 g/cm2 (p <0.0001), z-score from -3.77 to -2.44 (p
      <0.0001). Mean vertebral height improved by 17.3%, from 15.6 to 18.38 mm (p =
      0.07); plasma alkaline phosphatase decreased from 222 to 169 U/l (p = 0.0009) and
      urinary deoxypyridinoline crosslinks decreased from 26.7 to 21.8 nmol/mmol
      creatinine (p = 0.21). Two children with vitamin D insufficiency were
      concurrently treated. A significant association (r = -0.6, p = 0.008) was shown
      between age at start of treatment and percentage change in BMD after 2 years.
      CONCLUSIONS: Pamidronate treatment improves bone quality in children with mild
      types of OI. It ameliorates clinical symptoms, improves mobility, reduces
      fracture frequency and thus improves quality of life and in future is likely to
      reduce the severity and consequences of adult osteoporosis by improved peak bone
      mass in these children.

PMID- 15570989
TI  - Auxological, clinical and MRI findings in Taiwanese children with growth hormone
      deficiency.
AB  - Growth hormone deficiency (GHD) may be classified into partial isolated GHD
      (partial IGHD), severe IGHD or multiple pituitary hormone deficiency (MPHD) by
      the severity of GHD or associated with deficiency of one or more other anterior
      pituitary hormones during provocative tests. Morphological alterations on
      magnetic resonance imaging (MRI) in patients with GHD include pituitary
      hypoplasia, absence or interruption of pituitary stalk, and absence or ectopic
      posterior lobe. This study investigated the auxological, clinical severity, and
      anatomical characteristics of the pituitary hypothalamic region by MRI and
      correlated their relationships. We evaluated these parameters in 45 Taiwanese
      children with GHD (31 males and 14 females), aged from 3.13 to 17.91 years
      (10.5+/-2.5), who were divided into diagnostic subgroups of partial IGHD (18
      patients), severe IGHD (13 patients), and MPHD (14 patients). We found that BA
      CA, peak GH, IGF-I, IGF-I SDS, and height SDS were significantly different among
      these three groups. The partial IGHD group had significantly higher IGF-I than
      the MPHD group. There was no significant difference in prematurity, cesarean
      delivery, birth order, neonatal jaundice, and target height among these three
      groups. On MRI, patients with MPHD had significantly smaller pituitary height
      (PHt) SDS (p = 0.0012) and higher frequency of pituitary hypoplasia, pituitary
      stalk interruption, and ectopic posterior lobe (p = 0.026, 0.008, 0.005,
      respectively) than the other two groups. Furthermore, PHt SDS was correlated not
      only with peak GH (r = 0.40, p = 0.0058), but also with basal IGF-I SDS (r =
      0.49, p = 0.0007) and body height SDS (r = 0.44, p = 0.025). In conclusion,
      morphological alterations on MRI of the hypothalamic-pituitary area are
      correlated with the severity of hypopituitarism. Meticulous evaluation of
      auxological, clinical and MRI findings can help evaluation of the severity of
      hypopituitarism and facilitate appropriate treatment in children with GHD.

PMID- 15570990
TI  - Breast-fed infants have higher leptin values than formula-fed infants in the
      first four months of life.
AB  - BACKGROUND: Leptin is a hormone present in breast milk, which regulates food
      intake and energy metabolism. AIM: To investigate whether leptin levels are
      different in breast-fed (BF) or formula-fed (FF) infants in the first months of
      life. METHODS: We evaluated serum leptin by radio-immunoassay and anthropometric
      parameters in 51 infants at the average age of 62.8+/-30 days, 25 exclusively BF
      and 26 exclusively FF. RESULTS: Leptin serum values were higher in BF (7.1+/-10.4
      ng/ml) than in FF (3.7+/-3.87 ng/ml) infants (p <0.05). Leptin values were higher
      in females (6.9+/-9.87 ng/ml) than in males (3.5+/-3.88 ng/ml) (p <0.05). No
      differences were found in anthropometric measurements and body mass index.
      CONCLUSION: The kind of feeding might be a factor affecting serum leptin
      concentration in term infants. The long-term consequences of this difference
      between BF and FF infants and leptin's role in promoting obesity later in life
      are unknown.

PMID- 15570991
TI  - The impact of physiological, therapeutic and psychosocial variables on glycemic
      control in youth with type 1 diabetes mellitus.
AB  - OBJECTIVE: Intensive management of type 1 diabetes mellitus (DM1) in youth is
      challenging. We evaluated the relative impact of variables related to DM1 among
      groups of pre/early pubertal, midpubertal and postpubertal youths with DM1.
      METHODS: In this cross-sectional study of 153 youth with DM1, we ascertained
      Tanner stage, insulin dose and delivery modality (CSII vs MDI), daily blood
      glucose monitoring (BGM) frequency, and most recent hemoglobin A1c (HbA1c). We
      collected questionnaires from patients and their parents on diabetes-specific
      family conflict and family involvement in diabetes management tasks. We assessed
      predictors of glycemic control according to pubertal status. RESULTS: Insulin
      doses increased between pre/ early puberty and midpuberty (p <0.0001); daily BGM
      frequency (p = 0.02) and family involvement for DM management (p <0.001) were
      lowest in the postpubertal group. HbA1c was similar among all three puberty
      groups (8.4+/-1.4). Lower levels of child-reported DM-specific family conflict,
      more frequent BGM, and CSII use were significantly associated with lower HbA1c
      (R2 = 0.20, p <0.001). CONCLUSION: Although glycemic control was not
      significantly worse in midpubertal and post-pubertal patients, family involvement
      for DM management and adherence to BGM were lower in late adolescence.
      Interventions to optimize glycemic control may include minimizing DM-specific
      conflict, increasing BGM frequency, and implementing CSII use.

PMID- 15570992
TI  - Vulvovaginal candidiasis in children and adolescents with type 1 diabetes
      mellitus.
AB  - In this prospective study we investigated the frequency of vulvovaginal
      candidiasis, the results of yeast cultures and detection of ketoconazole
      resistance in female children and adolescents with type 1 diabetes mellitus
      (DM1). The study consisted of 35 patients with DM1 (age 1.7-20 years) and 22
      controls (age 1.5-18 years). Age, duration of DM1 and evidence of genital
      symptoms were recorded initially. After a pelvic examination, two separate swabs
      and samples for blood glucose and hemoglobin A1c (HbA1c) were taken. One of the
      swabs was used for direct examination and the second was placed on Sabouraud's
      dextrose agar and incubated. In vitro susceptibility of Candida species to
      ketoconazole was established by using Etest (AB B1ODISC). Candida species were
      isolated in 32 of 61 (52.5%) swabs of patients with DM1 and five of 22 (18.2%) of
      the control group. The predominant Candida species isolated from patients with
      DM1 were C. albicans (72.7%), C. glabrata (22.7%), C. tropicalis (2.3%), and C.
      parapsilosis (2.3%). The mean HbA1c in diabetic patients from whom Candida
      species were isolated was significantly higher than that of patients without
      Candida infection (p = 0.002). Most of the C. glabrata isolates were
      significantly resistant to ketoconazole. During the follow-up of patients with
      DM1, genital candidiasis is generally overlooked. It should not be forgotten that
      species other than C. albicans might cause genital candidiasis.

PMID- 15570993
TI  - Direct costs of care in germany for children and adolescents with diabetes
      mellitus in the early course after onset.
AB  - BACKGROUND AND OBJECTIVE: Prospective population-based cost-of-illness study to
      evaluate diabetes mellitus (DM)-related direct costs in German pediatric DM care
      in the early course after onset (perspective: statutory health insurers).
      PATIENTS AND METHODS: 573 patients with DM <15 years of age were followed for up
      to 2 years after onset. DM-related hospitalization and ambulatory care, insulin
      and self-testing regimen were ascertained. Costs per patient-year were estimated
      (2000 prices). Using multivariate regression, associations between costs and
      families' socioeconomic status was evaluated. RESULTS: Mean total costs per
      patient-year were 7,069 euro (interquartile range 5,414-8,127). Onset
      hospitalization accounted for the majority of costs (4,908 euro, 3,728-6,213).
      Within post-onset costs, most were attributable to blood glucose self measurement
      and hospitalization (36% and 32%). Costs were significantly higher in children
      from families with lower compared to highest educated parents and in children
      from non-German families (p <0.01). CONCLUSIONS: Among the direct medical costs
      of childhood DM in the early course after onset, the greatest economic burden was
      due to hospitalization, in particular at onset. Blood glucose self measurement
      accounted for the majority of the post-onset costs. Costs were associated with
      the socio-economic status. It is recommended to evaluate the cost-effectiveness
      of outpatient programs targeting children from families with lower social status.

PMID- 15570994
TI  - Short-term insulin therapy in adolescents with type 2 diabetes mellitus.
AB  - The optimum pharmacological treatment of type 2 diabetes mellitus (DM2) in youth
      for those who fail to achieve adequate glycemic control (HbA1c <7%) with
      lifestyle intervention is unknown. The aim of this pilot study was to observe the
      effect of short-term insulin therapy (<16 weeks duration) on glycemic control in
      youth with DM2. A pre-mix 30/70 insulin was given twice daily to 18 youth aged 10
      18 years with DM2 for 8.7+/-4.3 weeks with a starting dose of 0.5 U/kg/day.
      HbA1c, body mass index (BMI) and episodes of hypoglycemia were monitored during
      the treatment period and for a 12-month period after insulin was stopped. Mean
      HbA1c decreased from 12.81% to 7.59% (95% CI 6.54, 8.64). This improvement
      persisted for 12 months without any further drug therapy. There was no
      significant change in mean BMI and there were no episodes of moderate or severe
      hypoglycemia. Decreasing beta-cell glucose toxicity with rapid improvement of
      blood glucose may play an important role in treatment of DM2 in adolescents.
      Early success in achieving target blood glucose levels is an important aspect of
      adolescent DM2 care.

PMID- 15570995
TI  - Latent autoimmune diabetes mellitus in children (LADC) with autoimmune
      thyroiditis and Celiac disease.
AB  - Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical
      presentation as type 2 diabetes mellitus after 25 years of age, initial control
      achieved with oral hypoglycemic agents for at least 6 months, presence of
      autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An
      8.3 year-old girl was referred to our pediatric endocrinology department because
      of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight
      loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was
      126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide
      levels were normal, her first phase insulin response (FIR) was lower than the 1st
      percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti
      glutamic acid decarboxylase (antiGAD) were negative. According to the clinical
      and laboratory findings, she was diagnosed as having type 2 diabetes mellitus.
      She was started with oral anti-diabetic treatment for a period of 1 year. Insulin
      had to be initiated for worsening of HbA1c levels. In the fourth year of follow
      up, she was admitted to our hospital with diabetic ketoacidosis although she was
      on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD
      and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid
      peroxidase antibody and endomysium antibody were found to be high at follow-up.
      Small intestinal biopsy revealed celiac disease. This patient may represent the
      first case of latent autoimmune diabetes mellitus in children (LADC) with
      autoimmune thyroiditis and celiac disease.

PMID- 15570996
TI  - Female pseudohermaphroditism with phallic urethra in the offspring of a mother
      with an adrenal tumor.
AB  - BACKGROUND: Female pseudohermaphroditism is a disorder in which 46,XX females
      with ovaries do not develop as normal women. This disorder is caused by
      overexposure of a female fetus to androgens during intrauterine life. We describe
      a masculinized female infant who was born to a mother who had virilizing signs.
      PATIENT REPORT: The patient had a normally formed phallus and a completely fused
      scrotum. Baseline as well as stimulated adrenal hormones and testosterone values
      were in the normal range in the infant. No androgens were given to the mother
      during pregnancy. Serum 17-OHP, DHEA-S, and testosterone levels were all elevated
      in the mother. Imaging studies revealed a tumor mass over the left kidney pole.
      Histologically it was an adrenal tumor. CONCLUSIONS: Although a maternal adrenal
      tumor is a rare cause of female pseudohermaphroditism, the physician must bear
      this in mind when confronted with a newborn or infant with 46,XX karyotype and
      cryptorchidism with a phallic urethra.

PMID- 15570997
TI  - Graves' disease in DiGeorge syndrome: patient report with a review of endocrine
      autoimmunity associated with 22q11.2 deletion.
AB  - DiGeorge syndrome, which falls within a wider phenotypic spectrum associated with
      deletions of 22q11.2, is associated with a number of endocrine disorders. These
      include hypoparathyroidism, hypothyroidism and growth hormone deficiency. We
      report an unusual case of autoimmune hyperthyroidism (Graves' disease) presenting
      in a 3 year-old male with DiGeorge syndrome. The development of endocrine
      specific autoimmune disease in a syndrome associated with immune deficiency and
      the spectrum of endocrine autoimmunity associated with deletions of 22q11.2 are
      described. Paediatricians and patients with 22q11.2 deletions should be
      particularly aware of the risks of developing disorders of thyroid function.

PMID- 15570998
TI  - Role of viral and host factors in HCV persistence: which lesson for therapeutic
      and preventive strategies?
AB  - Several lines of evidence support the view that hepatitis C virus is not directly
      cytopathic for infected host cells and that the immune response plays a central
      role in the pathogenesis of liver damage. Innate and adaptive immune responses
      are induced in most individuals infected with hepatitis C virus but are
      insufficient to eliminate the virus. The mechanisms responsible for this failure
      are largely unknown but the kinetics of hepatitis C virus replication relative to
      the priming of the adaptive responses may exert a profound influence on the
      balance between virus and host. Immediately after hepatitis C virus infection,
      the virus replicates efficiently, inducing the production of type I interferons.
      However, the rapid increase in viral replication seems to be ignored by the
      adaptive immune response, and after a short interval from exposure, viral load
      can reach levels comparable to those of patients with established persistent
      infection. The CD8-mediated response shows functional defects, with impaired
      production of interferon-gamma, low perforin content, decreased capacity of
      expansion and lysis of target cells. Late appearance and functional defects of T
      cells in hepatitis C virus infection might be the result of the rapid increase of
      the viral load that could create the conditions for exhaustion of the adaptive
      response or reflect an insufficient function of the innate immune response. This
      possibility is suggested by in vitro studies showing that hepatitis C virus gene
      products can interfere with the anti-viral activity of type I interferons and
      natural killer cells as well as with the maturation of dendritic cells. While T
      cell defects are reversed in a minority of infected individuals who succeed in
      controlling the infection, the T-cell impairment becomes progressively more
      profound as infection progresses to chronicity. In this situation, therapeutic
      restoration of adaptive responses may represent a rational strategy to obtain
      resolution of infection and to complement available therapies. The peculiar
      kinetics of hepatitis C virus replication and T-cell induction soon after
      infection may have important implications also for the design of protective
      vaccines since memory responses may not be able to precede the early peak of
      viral replication. Therefore, vaccines against hepatitis C virus may be unable to
      prevent infection but may rather be effective in facilitating a self-limited
      evolution of infection.

PMID- 15570999
TI  - The international face of coeliac disease.

PMID- 15571000
TI  - Therapies for hepatic fibrosis: real hope or just academic exercise?

PMID- 15571001
TI  - Serum leptin level in patients with functional dyspepsia.
AB  - BACKGROUND/GOAL: Previous studies have shown that leptin plays a major role in
      the amount of food consumption. Recently, leptin and its receptors have been
      found in the human gastric mucosa. The aim of this study was to seek any possible
      correlation between serum leptin level and subtypes and pathological findings in
      functional dyspepsia. MATERIALS AND METHODS: In a prospective study, we randomly
      select 44 patients as dysmotility-like and ulcer-like dyspepsia (according to
      ROME II criteria) in two equivalent groups and compared them with 22 healthy
      volunteers control group who matched the patients in relation to age, sex and
      body mass index. From each patient, a fasting blood sample for leptin level and
      two antral biopsies for evaluating the intensity of gastritis and Helicobacter
      pylori infection were provided and compared with the control group. RESULTS:
      Compared to the control group, serum leptin level was significantly higher in
      patients with dysmotility-like dyspepsia (P < 0.05). Leptin level were also
      significantly correlated with the presence of gastritis and H. pylori infection
      (P < 0.05). CONCLUSION: Leptin may have a role in the pathogenesis of the
      dysmotility variety of non-ulcer dyspepsia through mechanisms other than H.
      pylori infection. Further studies based on gastric leptin immunohistochemistry
      may need correlation between symptoms of functional dyspepsia and gastric leptin
      expression.

PMID- 15571002
TI  - Epidemiological and clinical features in immigrant children with coeliac disease:
      an Italian multicentre study.
AB  - BACKGROUND: There are no available data concerning the incidence and the clinical
      pattern of coeliac disease in immigrant children coming to Italy from developing
      countries. AIMS: To evaluate the epidemiological and clinical features of coeliac
      immigrant children coming to Italy. PATIENTS AND METHODS: Hospital records of
      1917 children diagnosed in 22 Italian Centres from 1999 to 2001 as having coeliac
      disease were retrospectively reviewed, comparing immigrant patients versus
      Italian ones. RESULTS: 36/1917 (1.9%) coeliac children were immigrant. This
      prevalence was similar to that of the immigrant children among the whole
      paediatric population living in Italy. Prevalence was influenced by geographical
      factors, being higher in Northern Italy (1.7%) and in Central Italy (2.5%) than
      in Southern-Insular Italy (1.5%), as consequence of a higher proportion of
      immigrants in these regions. The native areas of the immigrant children were East
      Europe (15/36), Northern Africa (14/36), Southern Asia (4/36), West Africa
      (1/36), East Africa (1/36) and the Middle East (1/36). The clinical spectrum and
      dietary habits in immigrant patients were similar to those of the Italian
      children. CONCLUSIONS: Coeliac disease among the immigrant children coming from
      developing countries is an emerging problem, and physicians need to be fully
      aware of it. An important risk factor for coeliac disease in immigrant children
      appears to be sharing of the same dietary habits with the Italian population. The
      finding of coeliac disease in children coming from many countries worldwide
      suggests that coeliac disease is a global public health problem.

PMID- 15571003
TI  - Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the
      diagnosis of coeliac disease in patients with selective immunoglobulin A
      deficiency.
AB  - BACKGROUND: Selective IgA deficiency is associated with coeliac disease, and
      studies have shown an increased prevalence of coeliac disease in these patients
      ranging from 0.71 to 30.7%, depending on the test used for screening. AIMS: To
      determine the sensitivity of IgG anti-gliadin-antibodies and of IgG human-tissue
      transglutaminase for diagnosing coeliac disease and assessing its prevalence in
      subjects with IgA deficiency. SUBJECTS: We tested serum samples from 126 IgA
      deficient children (66 female, median age: 10.8 years). METHODS: All samples were
      analysed to measure IgG anti-gliadin-antibodies and IgG anti-human-tissue
      transglutaminase. Patients testing positive to either test underwent intestinal
      biopsy. Subjects testing positive for IgG anti-human-tissue-transglutaminase
      underwent genetic testing for the human leucocyte antigen heterodimer. RESULTS:
      Twenty-seven of 126 subjects tested positive for IgG anti-gliadin-antibodies
      (five of whom tested positive also for IgG anti-human-tissue-transglutaminase)
      and 18 (including the aforementioned five) for IgG anti-human-tissue
      transglutaminase. Intestinal biopsy was performed in 37 of the 40 patients who
      tested positive (three subjects refused). Eleven had positive intestinal biopsies
      all of whom tested positive for IgG anti-human-tissue-transglutaminase, but only
      five of these tested positive also for IgG anti-gliadin-antibodies. All 22
      patients testing positive for anti-gliadin-antibody alone had normal intestinal
      mucosa. All the patients who tested positive for IgG anti-human-tissue
      transglutaminase and underwent genetic screening (15/18) had the coeliac-related
      human leucocyte antigen. Overall, coeliac disease was diagnosed in 11 of the 126
      subjects with IgA deficiency (8.7%). CONCLUSIONS: The prevalence of coeliac
      disease in subjects with total IgA deficiency was 8.7%. Assay of IgG anti-human
      tissue-transglutaminase can be recommended for screening coeliac disease in IgA
      deficient subjects.

PMID- 15571004
TI  - Optimisation of isolation of richly pure and homogeneous primary human colonic
      smooth muscle cells.
AB  - BACKGROUND: Inherent properties of gastrointestinal smooth muscle can be assessed
      using isolated cell suspensions. Currently available isolation techniques, based
      on short 2-h enzymatic digestion, however, present the disadvantage of low
      cellular yield with brief viability. These features are an important limiting
      factor especially in studies in humans in which tissue may not be available daily
      and mixing of samples is not recommended. AIMS: To optimise the isolation
      procedure of cells from human colon to obtain a richly pure primary smooth muscle
      cell preparation. METHODS: Slices of circular muscle layer, obtained from
      surgical specimens of human colon, were incubated overnight in Dulbecco's
      modified eagle's medium supplemented with antibiotics, foetal bovine serum, an
      ATP-regenerating system and collagenase. On the following day, digested muscle
      strips were suspended in HEPES buffer, and spontaneously dissociated smooth
      muscle cells were harvested and used either immediately or maintained in
      suspension for up to 72 h. Cell yield, purity, viability, contractile responses,
      associated intracellular calcium signals and RNA and protein extraction were
      evaluated and compared to cell suspensions obtained with the current short
      digestion protocol. RESULTS AND CONCLUSION: The overnight isolation protocol
      offers the advantage of obtaining a pure, homogeneous, long-life viable cell
      suspension that maintains a fully differentiated smooth muscle phenotype
      unchanged for at least 72 h and that allows multiple functional/biochemical
      studies and efficient RNA extraction from a single human specimen.

PMID- 15571005
TI  - The anti-fibrotic effect of pirfenidone in rat liver fibrosis is mediated by
      downregulation of procollagen alpha1(I), TIMP-1 and MMP-2.
AB  - BACKGROUND: Pirfenidone (5 methyl-1-phenyl-2(1H)-pyridone) is a novel anti
      fibrotic agent, which has been shown to decrease collagen deposition in a variety
      of animal models in vivo, and recently in hepatic fibrosis also. At cellular
      level, we have recently demonstrated that pirfenidone is able to inhibit
      proliferation of hepatic stellate cells induced by platelet-derived growth
      factor, as well as collagen type I accumulation and alpha1(I) procollagen mRNA
      expression. AIMS: To evaluate if pirfenidone maintains its anti-fibrotic
      properties also when administered after the induction of hepatic damage and to
      further investigate the molecular mechanisms leading to the anti-fibrotic effect
      of pirfenidone. METHODS AND RESULTS: Rats treated with dimethylnitrosamine (10
      mg/kg) for 5 weeks received a liquid diet containing 0.5% pirfenidone starting
      from the third week. Pirfenidone treatment reduced the degree of liver injury, as
      determined by alanine aminotransferase values and necro-inflammatory score, which
      was associated with reduced hepatic stellate cells proliferation and collagen
      deposition. Treatment with dimethylnitrosamine increased transcripts levels for
      transforming growth factorbeta1, procollagen alpha1(I), tissue inhibitors of
      metalloproteinase-1 and matrix metalloproteinase-2 by 7-, 7-, 4- and 15-fold,
      respectively. Pirfenidone administration downregulated elevated levels of those
      transcripts by 50-60%, and this was associated with a 70% reduction in collagen
      deposition. CONCLUSIONS: (1) Pirfenidone is effective also if administered after
      the induction of the hepatic damage; (2) the anti-fibrotic effect of pirfenidone
      is mainly due to the reduced expression of profibrogenic procollagen alpha1(I)
      and TIMP-1, most likely through the downregulation of transforming growth
      factorbeta1 mRNA, and of matrix metalloproteinase-2, which is mainly implicated
      in the degradation of the normal extracellular matrix.

PMID- 15571006
TI  - Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in
      an Egyptian village: study description and 12-month results.
AB  - BACKGROUND/AIMS: A double-blinded trial evaluating silymarin, an herbal
      supplement for liver disease, to prevent complications of chronic hepatitis C
      virus infection has not been done. SUBJECTS: One hundred and seventy-seven
      consenting residents of an Egyptian village with chronic hepatitis C virus were
      randomly assigned to receive either silymarin or multivitamin supplements.
      METHODS: Participants had baseline and follow-up clinical, ultrasound, blood
      tests and quality-of-life assessments. Community nurses visited weekly to
      ascertain compliance, distribute supplements and record adverse effects. RESULTS:
      At 12 months almost all of 141 remaining subjects reported feeling better,
      although symptoms and quality-of-life scores did not differ between the silymarin
      and multivitamin groups. Both the silymarin and vitamins were tolerated equally
      well; and >95% of supplements were taken by >95% of subjects. One in each group
      had no detectable hepatitis C virus antibodies while two in the silymarin group
      and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum
      alanine aminotransferase elevations did not differ between groups. Serum hepatic
      fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results
      were similar in both groups and may have progressed slightly at 12 months.
      CONCLUSIONS: The recommended dose of silymarin can be safely taken for 1 year and
      improves symptoms and general well-being, but has no effect upon hepatitis C
      virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis.
      More prolonged evaluation and a higher dose may be required to ascertain whether
      milk thistle supplements prevent complications of chronic hepatitis C virus.

PMID- 15571007
TI  - Atypical gastric presentation of strongyloidiasis in HIV-infected patient--case
      report.
AB  - Strongyloides stercoralis is an intestinal helminth of systemic distribution,
      which, once in its host, has the ability to perpetuate itself through an
      autoinfection cycle, leading to chronic infection. In healthy hosts, the parasite
      usually does not cause any symptoms, or only mild symptoms that are limited
      mainly to the small intestine. However, in immunocompromised hosts, uncontrolled
      multiplication with massive infection may occur, causing hyperinfection syndrome
      or disseminated strongyloidiasis, which are both associated with high morbidity
      and mortality. There are few reports of gastric involvement, particularly
      presenting as ulcer in the stomach. We report a case of gastric ulcer caused by
      S. stercoralis in HIV-infected patient.

PMID- 15571008
TI  - An unusual cause of recurrent biliary colics.
AB  - Hepato-biliary ascariasis is a rare condition in non-endemic areas; however, it
      should always be taken into account in patients with recurrent biliary colics
      and/or cholangitis, since these are among the most frequent modes of clinical
      presentation. We report a case of a young woman suffering from recurrent biliary
      colics in whom a diagnosis of biliary ascariasis was made. Endoscopic retrograde
      cholangiopancreatography with sphincterotomy and endoscopic extraction of the
      worm, using a Dormia basket, proved to be a safe and effective procedure for
      removing the living Ascaris from the biliary tree and relieving symptoms. In the
      era of worldwide travels, physicians in Western countries should be more aware of
      this infection especially in patients with biliary symptoms who have travelled to
      endemic areas or immigrant from endemic countries.

PMID- 15571009
TI  - Efficacy of conventional immunosuppressive drugs in IBD.
AB  - The introduction and rapid diffusion of biological agents in the treatment of
      inflammatory bowel disease had led us to believe that the old immunosuppressive
      drugs were destined to disappear. However, despite a decade of clinical
      experience in the use of biological agents, the old immunosuppressive drugs
      continue to play a pivotal role in the management of inflammatory bowel disease.
      Various factors may account for this change of view. Aim of the present review
      was to summarise key information currently available regarding the use of
      immunosuppressive drugs in the treatment of inflammatory bowel disease.

PMID- 15571010
TI  - Coeliac disease and non-alcoholic fatty liver disease.

PMID- 15571011
TI  - Primary small bowel adenocarcinoma: a single centre evaluation of survival.

PMID- 15571012
TI  - Past, present and future of surgical training in Belgium.

PMID- 15571013
TI  - History and perspectives in laparoscopic vascular surgery.
AB  - Laparoscopic techniques have changed the face of many surgical specialties. In
      this article, we describe the evolution of laparoscopy in vascular surgery from
      its beginning in the early 1990s. We discuss the present laparoscopic techniques
      for treatment of aortoiliac disease, their advantages and limitations. We suggest
      the vascular surgeon learns laparoscopy on the model used in general surgery a
      decade ago. Although more studies are needed to further define the role of
      laparoscopy, present indications can be found in those patients with TASC III and
      IV occlusive lesions and in patients with abdominal aortic aneurysms who are
      candidate to tube grafts or aortobifemoral bypass. With further refinements in
      technology (anastomotic stapling device, robotics) and techniques, laparoscopy
      should replace many open surgeries presently done for aortoiliac disease but will
      also have to be considered for treatment of mesenteric disease as described in
      the text.

PMID- 15571014
TI  - Minimal-access aortic surgery: the potentials of hand-assisted laparoscopy.
AB  - In analogy with the good results of laparoscopic abdominal procedures minimal
      access aortic surgery looks very promising. However, in spite of the many
      technical improvements that have already been made, totally laparoscopic and even
      laparoscopically assisted aortic surgery remains technically demanding. This
      explains the rather slow introduction of minimal-access aortic surgery in the
      vascular society. In anticipation of increasing surgical experience and better
      instrumentation that will make the technique feasible for each vascular surgeon,
      hand-assisted laparoscopy (HALS) can be a valuable intermediate approach. HALS
      offers an easy to perform and still clearly less invasive approach for all aorto
      iliac reconstructions.

PMID- 15571015
TI  - Laparoscopic aortic surgery: recent development in instrumentation.
AB  - Beside conventional and endovascular techniques, laparoscopic surgery is becoming
      a third way to treat patients presenting with aortoiliac occlusive or aneurysmal
      diseases. Several different laparoscopic techniques have been described, but most
      authors are stressing on the need for development of a specific laparoscopic
      aortic instrumentation, in order to decrease the operative and clamping times and
      to reduce the learning curve. This article is presenting an overview of what is
      already available, as laparoscopic aortic clamps or laparoscopic intestinal
      retractor, and what is still experimental, like laparoscopic aortic staplers,
      anastomotic devices or robotic surgical systems. This important technologic
      challenge should lead to two major orientations: development of qualitative in
      vitro and in vivo experiments to test these new products and training courses to
      teach the manipulation of it. Minimally aggressive techniques are well adapted to
      a western population, which becomes older, and has access to constantly improving
      medical care; however, only a specific and ergonomic instrumentation will allow
      these new techniques to be widely embraced by the vascular surgical community.

PMID- 15571016
TI  - Endovascular treatment of acute type B aortic dissection.
AB  - Intervention is currently reserved in acute aortic dissection for Stanford Type A
      and for complications of Type B. Endovascular techniques such as fenestration of
      the intimal flap and stenting of vessel origins have been used to alleviate end
      organ ischaemia due to compromised branches. The introduction of stent grafts has
      offered a realistic alternative to surgery for Type B dissections. Closure of the
      primary entry tear encourages thrombosis of the false lumen, which is associated
      with good long-term outcome. Many questions remain unanswered and randomised
      controlled trials need to be performed to establish the role of stent grafts in
      uncomplicated Type B dissections, and the use of bare stents to encourage
      thrombosis of the more distal false lumen. Improvements in the design and
      engineering of stent grafts may help to establish endoluminal repair as the first
      line treatment of aortic dissection.

PMID- 15571017
TI  - Early complications in endovascular treatment of abdominal aortic aneurysm.
AB  - OBJECTIVE: The incidence of perioperative complications during endovascular
      repair of abdominal aortic aneurysm (EVAR) is reported in limited series. The aim
      of this study is to evaluate a multi-center survey of unexpected intraprocedural
      critical events of EVAR. METHODS: A questionnaire relative to intraprocedural
      complications during EVAR was sent to major vascular surgery divisions in Italy.
      Eleven answered to the survey. The data obtained are relative to 1696 procedures.
      RESULTS: A wide range of incidence of critical events was observed, from a lower
      value of 2.7% to a higher value of 68.8% (mean 21.16%). The problems relative to
      the insertion phase of the delivery system were 7.7%. Endoleaks were reported in
      5.5% of cases. Stent graft release was problematic in 0.4% of cases and in
      another 0.4% there was a problem in shaft retrieval. Unintentional coverage of
      renal or polar arteries occurred in 0.8% of the procedures ; hypogastric arteries
      were unwillingly excluded in 2.7% of cases. Aortic or iliac artery rupture had an
      incidence of 0.7% ; arterial dissection occurred in 0.9%, atheroembolism in 0.5%,
      lower limb ischemia due to graft limb kinks in 0.7% and to occlusion in 0.9%.
      CONCLUSIONS: Perioperative critical events represent a serious problem only in
      few cases of EVAR ; they are common but in many cases not predictable ; in most
      circumstances they can be easily corrected with adjunctive manoeuvres during the
      same procedure. There is a highly significant correlation between the total
      workload and the incidence of critical events ; these do not appear to be related
      to the learning curve.

PMID- 15571018
TI  - The role of the endovascular surgeon for lower extremity ischemia.
AB  - Since the data investigating endovascular therapy performed by surgeons is
      scarce, we retrospectively reviewed our experience of endovascular procedures
      performed by vascular surgeons in the operating room for lower extremity ischemia
      due to stenotic lesions. METHODS: A total of 14,424 procedures were performed by
      our division between January 1990--October 2003. Of these, 500 involved a balloon
      angioplasty. These made up 3.5% of the total caseload. The median age of the
      patients who underwent these 500 balloon angioplasty was 72+/-0.5 years old; 65%
      were male; 50% had a history of diabetes mellitus, and 6% had ESRD. Indications
      for the procedures included acute ischemia (47 cases), critical ischemia (rest
      pain, gangrene, or ischemic ulcers in 254 cases), failing bypass (64 cases),
      severe claudication (134 cases), and preoperative for a popliteal artery aneurysm
      repair. RESULTS: 244 of the procedures were percutaneous, and the remaining 256
      were combined with some type of open procedure. Those performed as an open
      technique were in combination with a bypass (135 cases) and in combination with a
      patch angioplasty (31cases). Balloon angioplasties were performed of the aorta (5
      cases), iliac arteries (281 cases), the superficial femoral artery (SFA) (101
      cases), the popliteal artery (44 cases), the tibial vessels (77 cases), the
      subclavian/axillary artery (5 cases) and failing grafts (26 cases). Balloon
      angioplasty was attempted in eight cases and failed due to inability to cross the
      lesion with a guidewire. Intraoperative complications included 4 dissections,
      inability to dilate the lesion adequately (2 cases), and rupture of two iliac
      lesions that underwent open repair (1 case) or repair with a stent graft (1
      case). Stents were initially used highly selectively but recently are now being
      deployed more liberally in the iliac arteries (total 251 cases with stents).
      CONCLUSIONS: Based on these data, we suggest that balloon angioplasty is a useful
      tool that can be performed by vascular surgeons safely. The advantages to the
      patients include one combined procedure to treat lower extremity ischemia.

PMID- 15571019
TI  - Iliac artery angioplasty : technique and results.
AB  - Percutaneous angioplasty is widely used for the treatment of iliac artery
      occlusive disease. Access to the ipsi-lateral, or less commonly contralateral,
      common femoral artery is obtained under local anaesthesia; the lesion is crossed
      with a guidewire and dilated with an angioplasty balloon catheter. This technique
      yields excellent immediate results with very few complications. Stent placement
      is used in lesions not amenable to balloon angioplasty, in complications, and
      recurrences. Evidence suggests that balloon angioplasty is the procedure of
      choice for iliac artery occlusive lesions. Stent placement should be reserved for
      angioplasty failures. However, primary stent placement is indicated in total
      occlusions. Lesion morphology is an important determinant of immediate success
      and long-term patency. TASC lesions type A and B are best treated with
      angioplasty and stenting, while TASC lesions type C and D show better results
      with surgical treatment. The development of new stent designs may expand the
      indications of the percutaneous treatment.

PMID- 15571020
TI  - The limits of percutaneous intervention in aortoiliac occlusive disease.
AB  - Aortoiliac occlusive disease (AIOD) is a common manifestation of atherosclerosis
      that may lead to limb-threatening ischemia. Over the past two decades,
      considerable advances in the management of patients with AIOD have taken place.
      Conventional surgical reconstructive procedures, namely aortofemoral and extra
      anatomic bypasses, tend to be replaced by newer emerging percutaneous techniques,
      such as angioplasty and stenting, initially employed to reduce morbidity,
      complications and cost of treatment. However, irrational application of these
      percutaneous techniques is not suggested, since these surgical procedures are not
      devoid of limitations. A careful evaluation of the various restraining parameters
      should precede the choice of surgical approach, to ensure the selection of the
      most suitable technique in each individual patient, on the grounds of clinical
      presentation of the disease and efficiency of the surgical procedure.

PMID- 15571021
TI  - Subintimial angioplasty, the way forward.

PMID- 15571022
TI  - Laparoscopic splenectomy for haematological diseases.
AB  - PURPOSE: To show the utility of laparoscopic splenectomy for hematologic
      diseases. PATIENTS AND METHODS: Ten patients with hematologic diseases who were
      operated between February 1997 and October 1998 were analysed retrospectively.
      TECHNIQUE: The operations were performed by four trocars, hilar vessels were
      divided by clips and bag was used for splenic retrival. RESULTS: All operations
      were completed successfully. No accessory spleens were found. Intraoperative
      complication, other than a bag tear in one operation did not occur. Postoperative
      complications occurred in two patients. The first one was a portal vein
      thrombosis and the second one was a peritonitis. All patients responded
      hematologically to the operation. CONCLUSION: With appropriate surgical technique
      and patient follow up, laparoscopic splenectomy is a safe, adventageous and
      efficaceus operation for hematologic diseases.

PMID- 15571023
TI  - Experience with benign splenic disease.
AB  - PURPOSE: In the ongoing effort to improve patient treatment, a deeper
      understanding of the symptomatology, physical signs and management options of
      rare splenic, non-traumatic, benign diseases is extremely important. PATIENTS AND
      METHODS: The records of eight consecutive patients with benign splenic
      conditions, other than injury and abscess, were reviewed retrospectively in order
      to analyse the clinical presentation, diagnostic methodology and therapeutic
      procedures applied in these rare conditions. Of the eight patients, three were
      diagnosed with splenic hydatid cyst, two with pseudocysts, one with splenic
      epidermoid cyst, one with wandering spleen and one with infraction of an ectopic
      spleen with situs inversus of other intra-abdominal organs. RESULTS: Upper
      abdominal pain was the most common presenting symptom and a tender palpable mass
      in the left upper abdominal quadrant, the predominant clinical finding. Pre
      operative CT scanning confirmed the diagnosis in six patients, but failed to
      reveal the splenic pathology in the remaining two cases. Seven patients underwent
      splenectomy while saving splenic parenchyma was feasible in only one patient
      (12,5%). CONCLUSIONS: Splenic, non-traumatic, benign diseases have vague clinical
      presentation and may create diagnostic difficulties. Although spleen saving
      intervention can be applied in selected cases, splenectomy would be required in
      most patients.

PMID- 15571024
TI  - Transcatheter management of hepatic artery pseudoaneurysm following
      pancreaticoduodenectomy: a report of three cases.
AB  - Pseudoaneurysm formation is a rare, but potentially life threatening delayed
      complication of major pancreatic surgery. Redo surgery several weeks after
      pancreaticoduodenectomy can be hazardous, especially in debilitated patients.
      Percutaneous, transcatheter exclusion of the pseudoaneurysm by means of embolic
      coils can be an efficient, safe and minimally invasive alternative to open
      surgery with good mid- and long-term results. We present our experience in Three
      patients undergoing transcatheter embolization of hepatic artery pseudoaneurysms
      detected several weeks after Whipple's operation.

PMID- 15571025
TI  - Coexistent thyroid pathologies and high rate of papillary cancer in patients with
      primary hyperparathyroidism: controversies about minimal invasive parathyroid
      surgery.
AB  - Thyroid carcinoma and benign thyroid diseases associated with primary
      hyperparathyroidism (PHPT) may cause difficulties in the diagnosis, localization
      and therapy of PHPT. In this study, we analysed coexistent thyroid pathologies in
      51 patients who underwent neck exploration with a diagnosis of PHPT between 1999-
      2002. Five hundred thirteen patients who underwent thyroidectomy for nodular
      thyroid disease without a parathyroid pathology in histopathological examination
      served as controls. In patients with PHPT there were 43 cases (84.3%) of
      coexistent thyroid pathology. Nine patients (17.6 %) had coexistent papillary
      thyroid cancer. Nine patients (17.6 %) had lymphocytic thyroiditis, two (3.9%)
      had benign thyroid adenoma and 24 (47%) had nodular hyperplasia. In one patient
      (2%), there was intrathyroidal metastasis from a parathyroid cancer. One patient
      had coexistent lymphocytic thyroiditis and multifocal papillary cancer. One of
      the two cases with thyroid adenomas was Hurthle cell type. In the control group
      only 28 patients (5.5%) had thyroid malignancy (27 papillary cancer and one
      follicular cancer). In conclusion, the coexistent thyroid pathologies are highly
      prevalent in patients with PHPT and pre- and intra-operative thyroid examination
      should be performed to avoid overlooking important thyroid pathologies.

PMID- 15571026
TI  - Simultaneous bilateral spontaneous pneumothorax report of 12 cases and review of
      the literature.
AB  - Simultaneous bilateral spontaneous pneumothorax (SBSP) is a very rare condition,
      mainly seen in patients with underlying lung disease. Up to now, there are 65
      patients who have been published. Twelve consecutive patients who presented with
      SBSP as definitive diagnosis were recruited for this study. They represented 1 %
      of all patients with spontaneous pneumothorax. All patients had immediate
      bilateral chest tubes on admission. Five of the 12 patients (42%) had no
      underlying lung disease. In 7 patients, SBSP was secondary to pulmonary
      metastases, histiocytosis X, undefined interstitial pulmonary disease,
      tuberculosis, pneumonia and chronic obstructive pulmonary disease. None of the
      patients died during hospitalization. Eleven patients were treated with chemical
      pleurodesis, whereas thoracotomy and pleurectomy were necessary in 7 patients.
      Reexpansion of the lungs was achieved in all patients. Immediate bilateral chest
      tube insertion and pleurodesis are of major importance in the treatment of SBSP
      although a subset of patients needed surgical pleurectomy. Combination of these
      treatments provides successful and uneventful treatment of the disease.

PMID- 15571027
TI  - The treatment of chronic anal fissure with botulinum toxin.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the effectiveness of
      botulinum toxin for the treatment of uncomplicated dorsal chronic idiopathic anal
      fissure. MATERIAL AND METHODS: Forty-five patients who reported post defecatory
      anal pain since two months or more were given a total of 20U botulinum toxin in
      the anal sphincter apparatus on both sides as well as below the anal fissure.
      RESULTS: Thirty-seven patients received a second session of 25U botulinum toxin
      injection. Thirty-five patients (78%) presented completely healed anal fissure,
      while ten needed lateral internal sphincterotomy. All patients were followed up
      for 8-36 months. Two patients relapsed. CONCLUSION: Local injection of botulinum
      toxin is a new and safe treatment; however, two sessions of injections are
      necessary to be effective and long-term follow-up to assess the recurrence rate
      of fissure is needed to evaluate further this method of treatment. Partial
      internal lateral sphincterotomy is no more the treatment of choice for chronic
      anal fissure.

PMID- 15571028
TI  - Expression of endothelin-1 by adrenocortical carcinoma: a new target for anti
      cancer therapy?
AB  - Adrenocortical carcinoma is a rare neoplasm with poor prognosis. Endothelin-1 (ET
      1) has been implicated in carcinogenesis, but has never been studied in this
      neoplasm. A 76-year-old woman with Cushing's syndrome due adrenocortical
      carcinoma was operated on and the tumour removed was studied by
      immunohistochemistry for ET-1. Patient history illustrates the poor prognosis of
      this cancer that became metastatic after one year. Immunohistochemical studies
      disclosed a strong expression of ET-1 by adrenocortical carcinoma cells. As shown
      in other cancers, ET-1 expression by adrenocortical carcinoma may suggest a
      pathogenic role of ET-1 in tumorigenesis that possibly could be countered by ET-1
      receptor antagonists. These agents could open new therapeutic perspectives to
      treat a carcinoma known to have a poor prognosis.

PMID- 15571029
TI  - Endovascular stent graft treatment for iatrogenic arteriovenous fistulas after
      femoral catheterisation.
AB  - This article presents a case report of a 79-year-old patient who was suffering
      from a large femoral arteriovenous fistula and a stenosis of the external iliac
      artery and who was treated successfully with stent grafts. The fistula, which
      consisted of three parts, was caused by a percutaneous transluminal coronary
      angioplasty. Two Jo-stents and one Medtronic AVE stent were used to cover the
      fistula and to dilate the stenosis. This article also describes the possible
      causes of iatrogenic arteriovenous fistulas such as the technique of arterial
      puncture and its localisation. The treatment of iatrogenic arteriovenous fistulas
      with stent grafts is a safe alternative for surgery in patients who often suffer
      from multiple cardiovascular problems. It could become the treatment of choice in
      the future.

PMID- 15571030
TI  - Small bowel obstruction during pregnancy.
AB  - The authors report the case of a 28-year old pregnant woman with abdominal pain
      and contractions at 37 weeks of gestation. After labour and delivery, abdominal
      pain persisted and laparoscopy was performed. A bowel obstruction was diagnosed
      and surgically corrected. The authors discuss the clinical and therapeutic
      consequences of bowel obstruction during pregnancy.

PMID- 15571031
TI  - Ruptured ectopic pregnancy presenting as an irreducible inguinal hernia.
AB  - An inguinal hernia that suddenly becomes irreducible may be secondary to a
      variety of other underlying conditions which can occasionally mislead the
      attending surgeon. Benign, inflammatory or neoplastic processes, as well as
      surgical emergencies such as intraperitoneal or retroperitoneal haemorrhage, have
      all been previously reported to mimic an inguinal hernia that suddenly becomes
      irreducible with or without clinical features of strangulation. We add an
      additional interesting presentation to this list in the form of a ruptured
      ectopic pregnancy, which is the first such case reported in the literature. A
      swelling in the groin may be much more complicated than it seems on superficial
      consideration and good clinical acumen is constantly required in managing such
      cases if a satisfactory outcome without any morbidity is to be expected.

PMID- 15571032
TI  - Manubriosternal disjunction a new approach for surgical repair.
AB  - We report a case of manubriosternal disjunction and review the literature. We
      describe a new approach for surgical repair with direct suture with PDS ropes.

PMID- 15571033
TI  - Spontaneous haemoperitoneum secondary to a Meckel's diverticulum.
AB  - Meckel's diverticulum is a relatively common gastrointestinal entity which
      occasionally causes complications. Meckel's diverticulum is classically described
      to mimic acute appendicitis when inflamed as well as being a cause of unexplained
      luminal gastrointestinal bleeding. An unusual cause of spontaneous non traumatic
      haemoperitoneum found during surgery performed for a suspected acute appendicitis
      in a 22-year old female is described. The patient was found to have a significant
      haemoperitoneum due to a bleeding serosal vessel of a Meckel's diverticulum. The
      diverticulum was routinely excised. It was macroscopically and histologically
      devoid of inflammation. The bleeding vessel was not found to be abnormal or part
      of an arteriovenous malformation.

PMID- 15571034
TI  - Scrotal skin metastases of renal cell carcinoma: a case report.
AB  - A 52-year old male, with a history of radical nephrectomy due to renal cell
      carcinoma ten years ago, presented with a lesion on the scrotum which was
      diagnosed as a metastasis of renal cell carcinoma.

PMID- 15571035
TI  - Isolated hepatic tuberculous pseudometastasis co-existent with adenocarcinoma of
      the stomach; report of a case.
AB  - A 10 x 9 mm metastasis-like lesion in segment V of the liver was detected, when a
      70-year-old man was operated on for adenocarcinoma of the stomach. Since exact
      diagnosis of the hepatic lesion could not be made by frozen sections, the lesion
      was excised, considering it to be a metastasis of gastric adenocarcinoma.
      Bacteriologic and pathologic studies established a diagnosis of isolated
      tuberculosis of the liver. A good response to antituberculous drug therapy was
      noted.

PMID- 15571036
TI  - [Activation of total and ribosomal RNA transcription under adapting doses of
      ionizing radiation inducing displacement of chromosome loci in human G0
      lymphocyte].
AB  - As we demonstrated earlier, the adapting X-ray doses (3 and 10 cGy) induced
      movement of chromosome centromeric loci in G0-lymphocyte nuclei. In the present
      study we investigated the influence of X-rays with 3 and 10 cGy doses on the
      content of total, 18S and 45S rRNA in human G0-lymphocytes because it is known
      that the transcription products participate in nucleus organization. It was shown
      that 3 h after irradiation the content of both total and 18S RNA was
      significantly increased. The 3 cGy dose induced higher level of the rRNA than 10
      cGy dose did in cells of some individuals. At the same time, the 45S RNA content
      was not changed significantly. This result may suggest that process of rRNA
      transcription and primary transcript (45S rRNA) processing have been completed
      during 3 h after irradiation. The data about an activation of rRNA synthesis were
      confirmed by cytological observation. Under 3 and 10 cGy doses both nuclei
      diameter and area of the Ag-stained granules were increased, depending on dose.
      These data also may be connected with an initiation of rRNA transcription because
      of correlation of Ag-painting with nucleolus activity. Thus, adapting X-ray doses
      induce displacement of chromosome loci in lymphocyte nuclei and activation of
      rRNA transcription. Further investigations are required for understanding of
      these phenomena interconnection.

PMID- 15571037
TI  - [ADP-ribosylation of proteins in nuclei and mitochondria from tissues rats of
      various age exposed gamma-radiation].
AB  - Constitutive and gamma-induced ADP-ribosylation of nuclei and mitochondrial
      proteins in 2- and 29-month-old rats was studied. ADP-ribosylation was determined
      by binding of [3H]-adenin with the proteins after incubation of cellular
      organells in reaction mixture supplemented with [adenin-2,8-3H]-NAD. It was
      detected that the level of total protein ADP-ribosylation in the nuclei is 4.5
      6.2 times higher than in the mitochondria. By inhibition of poly(ADP-ribose)
      polymerase (PARP) with 3-aminobenzamidine and treatment of ADP-ribosylated
      proteins with phosphodiesterase I, it was demonstrated that about 90% of [3H]
      adenin bound by proteins in the nuclei and 70% in the mitochondria was the result
      of PARP activity. The level of total ADP-ribosylation of nuclear and
      mitochondrial proteins in the tissues of old rats was reliably lower than in
      young animals. This reduction of ADP-ribosylation in old animals is the result of
      the lower activity of PARP, not of mono(ADP-ribosyl) transferase (MART). The
      level of ADP-ribosylation of proteins in the nuclei of brain and spleen cells of
      2-month-old rats irradiated with of 5 and 10 Gy was by 49-109% higher than in the
      control. At the same doses of radiation, the level of ADP-ribosylation of nuclear
      proteins in brain and spleen of old rats increased only by 29-65% compared to the
      control. Unlike cell nuclei, the radiation-induced activation of ADP-ribosylation
      in mitochondria was less expressed: the level of ADP-ribosylation increased by 34
      37% in young rats and by 11-27% in old animals. This increased binding of ADP
      ribose residues by the proteins of nuclei and mitochondria from tissues of gamma
      irradiated rats is exceptionally conditioned by activation of poly(ADP
      ribosyl)ation because the level of mono(ADP-ribosyl)ation remains constant. The
      results of this study enable the suggestion that poly(ADP-ribosyl)ation also
      occurs in the mitochondria of brain and spleen cells of the gamma-irradiated
      rats, though less pronounced than in cell the cell nuclei of these tissues. Thus,
      one of the probable causes of the less efficient repair of radiation-induced DNA
      damage in old organisms is a decline of both constitutive and induced poly(ADP
      ribosyl)ation of proteins in cell nucleus and mitochondria.

PMID- 15571038
TI  - [Sexual differences in a state systems of DNA structure maintenance and
      generation of reactive oxygen species in somatic cells of mice 101/H reparation
      defective strain and manifestation of these differences after exposure to
      ionizing radiation].
AB  - To analyse a role of the factor of a genetic fundamentals of cells in formation
      of radiation-induced genome instability (RIGI) we investigated a condition of DNA
      pattern, content of superoxide anion-radical O2*- and a sum of reactive oxigen
      species (ROS) (O2*-, OH*, H2O2), and also catalase activity in bone marrow cells
      of male and female mice of 101/H strain in the norm and at once after chronic (10
      day) exposure to 200 mGy gamma-radiation. Thus we based on conception about a
      significance of mechanisms of DNA repair and production of reactive oxygen
      species (ROS) in development of radiation-induced genome instability (RIGI), and
      also on the data on sex bound differences in efficiency of DNA repair in reply to
      impact of the genotoxic agents for male and female mice of 101/H strain. Sex
      connected differences in redox system of bone marrow cells were established. In
      males lower catalase activity was found in the norm, with considerable increase
      of the activity and the content of ROS after chronic irradiation with a low dose
      (200 mGy); at the same time a direct correlation between the ROS content and
      catalase activity occurred. In female, which have higher DNA repair potential,
      higher level of catalase activity was found in the norm, with reduction after
      irradiation and lower, than in male, level of O2*- content; no changes in the
      general ROS content, or direct correlation between the content of a superoxide
      anion-radical (O2*-) and the sum of ROS were observed. The detected differences
      between male and female the studied parameters in the norm and after irradiation
      indicate a connection of the studied characteristics and their changes with a
      sex, confirm the literature data about a significance of the factor of a genetic
      fundamentals of bioobject in formation of radiation-induced genome instability.

PMID- 15571039
TI  - [Ex vivo EPR investigation of metabolic changes in mice treated with
      radiotoxins].
AB  - The effect of radiotoxins (RT), obtained from gamma-irradiated potato tubers, on
      mice have been investigated using ex vivo EPR. Parts of liver, lung, spleen,
      heart and kidney were used for investigation. The amount of the preparations
      injected was 0.2 ml, RT concentration varying from 0.1 to 1 LD100 (LD100 = 100
      mg/kg). An intraperitoneal injection of RT in dose of 0.1 LD100 resulted in
      metabolic changes only in spleen. During 8 hours after injection a gradual
      depression of enzyme ribonucleotide reductase activity in spleen has been
      observed. After the treatment of mice with a lethal dose of RT signals from
      nitrosyl complexes have been appeared in spectra from all tissue investigated.
      The intensities of lines depend both on a time passed after treatment and a
      sensitivity of tissue to RT action. One of the main reasons of the lethal outcome
      of mice treated with RT may be the breaking of the compensatory adaptive response
      due to enhanced hypoxic state resulting from the high concentration of nitrosyl
      complexes generated in the tissue.

PMID- 15571040
TI  - [In vitro and ex vivo EPR investigation of metabolic changes in blood under the
      action of radiotoxins obtained from irradiated potato tubers].
AB  - The effect of radiotoxin (RT) obtained from y-irradiated potato tubes on blood of
      sheep and mice has been investigated by using in vitro and ex vivo EPR. In
      experiments in vitro, the action of different preparations (RT, extract from
      unirradiated potato tubers, 1%-HCl or 30%-hydrogen peroxide) on sheep blood has
      been compared. It has been established that RT is an effective oxidant (like 1%
      HCl) of haem iron that leads to an increase of the methemoglobin concentration.
      The specific peculiarity of RT effect on blood in vitro is an appearance of two
      well-resolved lines from methemoglobin belonging, probably, to different
      paramagnetic centers. The signal from nonspecific complexes of Fe3+ has been also
      observed. Ex vivo EPR spectra markedly differ from these obtained in experiments
      in vitro. An additional line with g approximately 2.005 and width 6 G in 30
      minutes after intraperitoneal RT injection in the lethal dose (0.2 ml of
      preparation containing of 2 mg RT) has been revealed. Subsequent intoxication of
      mice is accompanied by the appearance of the signal from nitrosyl complexes in
      EPR spectra. These differences in experimental results of in vitro and ex vivo
      EPR can be explained by launch of compensatory adaptive response of organism on
      the action of highly toxic preparation.

PMID- 15571041
TI  - [Functional and morphological characterization of rat thyroid gland at remote
      periods following single high and low dose radiation exposure].
AB  - A study of the morphological structure and functional activity of the rat thyroid
      gland was carried out after 22 months following a single exposure to external
      radiation. The 3-month-old animals were irradiated with doses of 0.25, 0.5, 1.0,
      2.0 and 5.0 Gy. Blood was assayed for thyroxin (T4) and triiodothyronine (T3)
      levels, while liver tissue--for NADP-MDH activity and thyroid tissue--for
      thyroperoxidase activity. The thyroid was studied histologically,
      morphometrically and by electron microscope. The decreased T4 concentrations 2.59
      fold in the 5.0 Gy group, the increased T3/T4 in the 2.0 and 0.25 Gy groups, the
      reduced diameter of cellular nuclei and follicles, the flat follicular epithelium
      and diminished number of thyrocyte ultrastructures indicate thyroid hypofunction
      in the irradiated animals. The morphological changes are characterized by
      enhanced diffuse and focal sclerotic changes in thyroid, most pronounced at high
      irradiation doses (1.0-5.0 Gy), whereas the hemosiderosis foci suggest that the
      structural changes are consequences of radiation-induced destructive injuries in
      the gland parenchyma. Two of the thyroids (0.5 Gy) demonstrate foci with
      pronounced lymphoid infiltration, while follicular carcinomas were detected in 4
      thyroids (2.0 Gy), and in one thyroid (0.5 Gy) in one thyroid (5.0 Gy). The
      remote effects of radiation were dose-dependent destructive, sclerotic and
      atrophic processes, decreased functional activity, stimulation of development of
      autoimmune aggression and carcinogenesis in thyroid.

PMID- 15571042
TI  - [Susceptibility of irradiated animals to extremely dangerous pathogens
      (literature review)].
AB  - The review is dedicated to the susceptibility of irradiated animals anthrax,
      tularemia and other extremely dangerous infection diseases. Live vaccine strains
      application in irradiated animals and antibacterial drugs efficiency under
      conditions of combined effects of radiological and biological agents are
      reviewed. As a conclusion the list of unsolved research problems is proposed.

PMID- 15571043
TI  - [Medical-prophylactic properties of the low-molecular-weight chitosan at
      environmental radiation injury].
AB  - The possibility of the successful modification of radiation injury by chitosan
      with low molecular weight (10 kDa) has been established under experimental
      conditions. The survival of mice increased up to 72.7 and 44.7% respectively at
      intravenous and intramuscular injection 30 min before gamma-irradiation with a
      dose 8 Gy (LD97). In guinea pigs the effect was 50-52.6% at intravenous and 40%
      at intramuscular administration 1-3 h after irradiation with a dose 5 Gy (LD90).
      Radioprotective efficiency of 10 kDa chitosan is close to that of high-molecular
      weight (65-70 kDa) preceding (medicine RS-10 and RS-11).

PMID- 15571044
TI  - [Radiation modulating properties of derivates of 1,4-dihydropyridine and
      1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8 dione].
AB  - First attempt to analyse radiation modifying action of 52 compounds--derivatives
      of 1,4-dihydropyridine is presented. Many of these compounds have electrodonating
      and antioxidative activities. Local radioprotective effects of the substances has
      been studied using experimental model with partial beta- and X-rays exposure of
      sole skin in rats to doses of 40 and 30 Gy. Comparison of drug effectiveness and
      chemical structure revealed the changes of activity dependence due to
      modification of peripheral radicals of 1,4-dihydropyridine ring. Radioprotective
      and radiosensitizing compounds with general low toxicity have been found. It is
      suggested to use the most active compounds for the development of medicinal forms
      for prevention of local skin and mucosal radiation injuries. Positive results
      have been obtained with dieton a radioprotective compound of the same type, in
      radiotherapy.

PMID- 15571045
TI  - [Development of tissue intoxication in the exposed rats and the effect of
      sorbents of different chemical structure].
AB  - In experiments with Wistar rats exposed to 7.5 Gy, polycationic sorbent ICHANT
      with gel structure and pores of various size exhibited stronger antitoxic
      properties as compared to carbon sorbents.

PMID- 15571046
TI  - [Radioprotective efficacy of chitosan, dissolved in aqueous extract of Abies
      Sibirica].
AB  - In experiments on rats it has been shown, that radioprotective efficacy of water
      soluble low-molecular chitosan (MM 23 kDa) used in a dose 5 mg/kg (per os 5
      ml/kg, daily ten-day treatment after whole-body irradiation with LD90/30) is
      higher, when it is dissolved in Abisib (aqueous extract of Abies Sibirica fir
      needles) in comparison with chitosan dissolved in distilled water. Survival rate
      and average life significantly increase. Radioprotective efficacy of water
      soluble low-molecular chitosan in a dose 5 mg/kg dissolved in distilled water or
      in Abisib (Chitabis) has been estimated. In comparison with control rats exposed
      to LD90/30, Chitabis administration (per os 5 ml/kg, daily ten-day treatment)
      leads to increase of average life from 15.44 +/- 2.31 to 28.37 +/- 3.09 days and
      of survival rate from 9.75 +/- 7.75% to 34.0 +/- 3.6%.

PMID- 15571047
TI  - [Long-term follow-up cytogenetic survey and biological dosimetry in persons
      evacuated from 30-km Chernobyl NPP zone].
AB  - The paper presents the results of the follow-up cytogenetic survey and biological
      dosimetry carried out in inhabitants of Pripiat' town and nearby villages, who
      were departured from the Chernobyl NPP 30-km exclusive zone during first days
      after the Chernobyl catastrophe. The unstable chromosome aberration level in
      inhabitants were significantly increased above control in terms up to 1 year
      after evacuation and declined gardually during next 14 years. In early period the
      cytogenetic damage frequency in evacuees showed no dependence on gender. The
      chromosome type aberration level appeared to be lower in young persons comparing
      with adults. The dicentrics plus centric rings yield had a positive correlation
      with duration of staying at Chernobyl zone. The average doses of protracted
      exposure were calculated from the dicentrics and centric rings yields; the dose
      estimations appeared to be 1.4 times higher in persons evacuated 3-11 days after
      the accident than that of in persons with shorter departure time. Uing the
      Bayesian analysis the probabilistic distribution of biological doses was
      constructed for the studied evacuees group. This distribution was characterized
      by a mean dose of 360 mGy, the modal doses of 200-450 mGy and 80% of probability
      density within the dose range 0-1000 mGy, that seems to be sufficient for
      considering the increased risk of late somatic radiation effects for this cohort.

PMID- 15571048
TI  - [Isolation and investigation of natural yeast strains resistant to heavy metal
      salts and radionuclides].
AB  - The collection of yeasts (more than 2000 strains) from extreme natural
      environment of Kamchatka peninsular and Kuril Islands was created. 448 strains
      were selected for their resistance to salts of such heavy metals as Cu, Cd, Co
      and to high temperature (37-52 degrees C). 72% of strains appeared to be
      resistant to one or more selective factors. We obtained several strains able to
      grow on medium with 0.1 M/L nonradioactive strontium and (or) cesium. Four of
      this strains accumulated radioactive isotope 90Sr with 45-80% efficiency. Thus,
      we demonstrated that yeast strains from nature could be used for bioremediation
      of industrial waste solutions, polluted by radionuclides and salts of heavy
      metals.

PMID- 15571049
TI  - [Variability of enzyme systems in the coenopopulation of Taraxacum officinale
      s.l. from the zone of East-Ural- radioactive trace].
AB  - Levels of soil contamination with 90Sr and 137Cs radionuclides on the plots
      within the zone of Eastern-Ural radioactive trace exceed values of the global
      level 4-240 times. We have carried out allozyme analysis of apomict species
      Taraxacum officinale s.l. from this zone. Zimogrammes were interpreted as
      allozyme phenotypes. In condition of chronic irradiation the plants had increased
      phenogenetic variability of majority enzymes systems and high frequency of rare
      morphs. Thus, in plant coenopopoulations situated in radioactive-polluted zone,
      genomic recombination processes show higher intensity. High enzymatic variability
      provides the material for natural selection and increase the adaptive potential
      of coenopopulations.

PMID- 15571050
TI  - [The effect of pulsed cyclical microware radiation on the conditioned behavior of
      rats].
AB  - Research has been carried out to investigate the effects of pulsed cyclical
      microware exposure (7 GHz, 400 pps, 100 mcs, 10-20 mW/cm2, 10 or 20 cycles of "5
      min exposure--4 min pause") on avoidance learning of rats. It was shown that
      reductions in conditioned behavior after cyclical pulsed microware exposure
      occurred at an SAR of 2.1 W/kg (10 mW/cm2). It was found the cumulation of the
      effects of the cycles at prolonged cyclical microwave exposures.

PMID- 15571051
TI  - [Modelling of 137Cs migration in agroecosystems under safety and rehabilitation
      measures].
AB  - Mathematical model describing dynamics of 137Cs transfer in agroecosystems under
      rehubilitation measures on arable, haylands, pastures and natural meadow
      ecosystems is presented. Possibilities of the model application for prediction of
      the radionuclide content in agricultural production and estimation of efficiency
      of countermeasures in region of the ChNPP accident are shown.

PMID- 15571052
TI  - [Radioecological situation at the villages of the Techa river].
AB  - The Techa river was contaminated in 1949-1956 from the nuclear enterprise
      "Mayak". The investigations were carried out in flood plain of the Techa river in
      1992-2001. 90Sr and 137Cs stores were calculated in the soil-vegetation cover.
      There is uneven character of the spatial radionuclides contamination of the
      investigated area. The store with 90Sr changes from 25 to 930 kBq/m2 (0.7-25.0
      Ci/km2) and that with 137Cs--from 30 to 1700 kBq/m2 (0.8-46.0 Ci/km2). In the
      preriver-bed soils the ratio 90Sr/137Cs increases with further from discharge
      point. Individual effective dose was calculated for the Brodocalmak population.
      90Sr was revealed in the flood plain soils of the Iset river. The contribution of
      the contaminated Techa river and its flood plains soils accounted for as by
      incorporated radionuclides as background gamma-radiation does not exceed 0.13
      0.17 mSv/yr if the contaminated Techa river utilization is limited. In other case
      the contribution of the contaminated Techa river increases to 1.6-3.0 mSv/yr.
      These values exceed international safety norms.

PMID- 15571053
TI  - Hyperbaric oxygen to treat malignant external otitis.

PMID- 15571054
TI  - Pain relief in those recovering from chemical dependency.

PMID- 15571055
TI  - The 2001 ASCCP management guidelines for cervical cytology.

PMID- 15571056
TI  - Overcoming the challenges facing quality-improvement strategies for non-ST
      segment elevation acute coronary syndromes.

PMID- 15571057
TI  - Management of cervical cytologic abnormalities.
AB  - The American Society for Colposcopy and Cervical Pathology developed guidelines
      in 2001 for the management of cervical cytologic abnormalities. The guidelines
      incorporate the Bethesda System 2001 terminology and data from randomized studies
      of atypical squamous cells, low-grade intraepithelial lesions, human
      papillomavirus testing, and liquid-based cytology to formulate evidence-based
      recommendations. Each recommendation is graded according to the strength of the
      recommendation and the quality of the evidence, and specific terminology is added
      to highlight management options. The effectiveness of each triage recommendation
      is determined by the percentage of grade 2 and 3 cervical intraepithelial
      neoplasia it detects. Colposcopy, repeat cytology, and human papillomavirus DNA
      testing are acceptable options in women with atypical squamous cells of
      undetermined significance, but human papillomavirus DNA testing is preferred if
      liquid-based cytology is used. Colposcopy is recommended for women with a
      diagnosis of "atypical squamous cells-cannot rule out high-grade intraepithelial
      lesion." Women with low-grade squamous intraepithelial lesions should be referred
      for colposcopy, and women with high-grade lesions should undergo colposcopy and
      endocervical assessment. Colposcopy and endocervical sampling are recommended in
      women with all subcategories of atypical glandular cells. Endometrial sampling
      and colposcopy are recommended in women older than 35 years with atypical
      glandular cells and in younger women with unexplained vaginal bleeding. Women
      with a diagnosis of "atypical glandular cells-favor neoplasia" or adenocarcinoma
      in-situ who are not found to have invasive disease on colposcopy should undergo a
      diagnostic excisional procedure, preferably a cold-knife conization.

PMID- 15571058
TI  - Chronic kidney disease: prevention and treatment of common complications.
AB  - Chronic kidney disease is a progressive condition that results in significant
      morbidity and mortality. Because of the important role the kidneys play in
      maintaining homeostasis, chronic kidney disease can affect almost every body
      system. Early recognition and intervention are essential to slowing disease
      progression, maintaining quality of life, and improving outcomes. Family
      physicians have the opportunity to screen at-risk patients, identify affected
      patients, and ameliorate the impact of chronic kidney disease by initiating early
      therapy and monitoring disease progression. Aggressive blood pressure control,
      with a goal of 130/80 mm Hg or less, is recommended in patients with chronic
      kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin-II
      receptor antagonists are most effective because of their unique ability to
      decrease proteinuria. Hyperglycemia should be treated; the goal is an AIC
      concentration below 7 percent. In patients with dyslipidemia, statin therapy is
      appropriate to reduce the risk of cardiovascular disease. Anemia should be
      treated, with a target hemoglobin concentration of 11 to 12 g per dL (110 to 120
      g per L). Hyperparathyroid disease requires dietary phosphate restrictions,
      antacid use, and vitamin D supplementation; if medical therapy fails, referral
      for surgery is necessary. Counseling on adequate nutrition should be provided,
      and smoking cessation must be encouraged at each office visit.

PMID- 15571059
TI  - Chronic kidney disease.

PMID- 15571060
TI  - Diagnosis and management of multiple sclerosis.
AB  - Multiple sclerosis, an idiopathic inflammatory disease of the central nervous
      system, is characterized pathologically by demyelination and subsequent axonal
      degeneration. The disease commonly presents in young adults and affects twice as
      many women as men. Common presenting symptoms include numbness, weakness, visual
      impairment, loss of balance, dizziness, urinary bladder urgency, fatigue, and
      depression. The diagnosis of multiple sclerosis should be made by a physician
      with experience in identifying the disease. Diagnosis should be based on
      objective evidence of two or more neurologic signs that are localized to the
      brain or spinal cord and are disseminated in time and space (i.e., occur in
      different parts of the central nervous system at least three months apart).
      Magnetic resonance imaging with gadolinium contrast, especially during or
      following a first attack, can be helpful in providing evidence of lesions in
      other parts of the brain and spinal cord. A second magnetic resonance scan may be
      useful at least three months after the initial attack to identify new lesions and
      provide evidence of dissemination over time. It is critical to exclude other
      diseases that can mimic multiple sclerosis, including vascular disease, spinal
      cord compression, vitamin B12 deficiency, central nervous system infection (e.g.,
      Lyme disease, syphilis), and other inflammatory conditions (e.g., sarcoidosis,
      systemic lupus erythematosus, Sjogren's syndrome). Symptom-specific drugs can
      relieve spasticity, bladder dysfunction, depression, and fatigue. Five disease
      modifying treatments for multiple sclerosis have been approved by the U.S. Food
      and Drug Administration. These treatments are partially effective in reducing
      exacerbations and may slow progression of disability.

PMID- 15571061
TI  - Acute shoulder injuries.
AB  - The shoulder is the most mobile joint in the human body. The cost of such
      versatility is an increased risk of injury. It is important that family
      physicians understand the anatomy of the shoulder, mechanisms of injury, typical
      physical and radiologic findings, approach to management of injuries, and
      indications for referral. Clavicle fractures are among the most common acute
      shoulder injuries, and more than 80 percent of them can be managed
      conservatively. Humeral head fractures are less common and usually occur in
      elderly persons; 85 percent of them can be managed nonoperatively. Common acute
      soft tissue injuries include shoulder dislocations, rotator cuff tears, and
      acromioclavicular sprains. Acromioclavicular injuries are graded from types I to
      VI. Types I and II are treated conservatively, types IV to VI are treated
      surgically, and there is debate about the best approach for type III. Eighty
      percent of shoulder dislocations are anterior. Diagnosis of this injury is
      straightforward. The injury usually can be reduced by employing a number of
      nonsurgical techniques. Traumatic or acute rotator cuff tears can be managed
      conservatively or surgically, depending on the patient and the degree of injury.

PMID- 15571062
TI  - Prognosis for patients undergoing coronary angioplasty.

PMID- 15571063
TI  - Reticular abdominal hyperpigmentation.

PMID- 15571064
TI  - Studies on bacterial conjugational crosses via model populations. I. The model
      populations.
AB  - A procedure is presented in which model populations, simulating progenies
      obtained from Escherichia coli Hfr x F- crosses, are generated. The procedure
      seems to be appropriate for visualizing hidden features of the genetic analysis,
      which are not detected by the conjugational crosses.

PMID- 15571065
TI  - Studies on bacterial conjugational crosses via model populations. II. Genetic
      studies.
AB  - Model populations, simulating progenies obtained from Escherichia coli Hfr x F-
      crosses, are generated. Linkage relations and exchange frequencies are expressed
      in these populations in complex, in some cases, even paradoxical manner. It is
      demonstrated that the origin of the complexities is located in the particular
      allelic configuration of the genotypes, characteristic for all exconjugant and
      selected populations.

PMID- 15571066
TI  - Tumour necrosis factor-alpha and heat-shock protein 70-2 gene polymorphisms in a
      family with rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this work was to investigate the prevalence of TNF-alpha
      308 polymorphism among the 29 members of a family with RA and the association
      between the MHC-linked biallelic HSP70-2 gene and the TNF-alpha polymorphism.
      Five of the members with RA were diagnosed by using the revised 1987 ACR
      criteria, and 1 member suffered from SLE. METHODS: The variations in the TNF
      alpha and the HSP70-2 genotypes were analyzed by PCR-RFLP, using NcoI and PstI
      restriction enzymes. RESULTS: Two of the 29 members were homozygotes for allele
      A, 18 were heterozygotes (TNF A/G) and 9 of them were homozygotes for allele G.
      Nineteen of the 29 were heterozygotes for HSP70-2 (A/G), 10 of them were
      homozygotes for the G allele, and none were homozygotes for allele A. Four of the
      5 the RA patients carried the A allele for TNF-alpha all 5 were heterozygotes for
      HSP70-2 genotypes. CONCLUSION: The carriage of the A allele for TNF-alpha of -308
      SNP in 4 of the 5 RA patients, and the high prevalence (68.0%) of TNF A allele
      carriers in this family confirms the important role of this candidate gene in the
      pathomechanism of RA, and might be of prognostic value for future clinical
      observations. Further, to test for association a much larger set of genetically
      independent patients and controls is needed.

PMID- 15571067
TI  - Etest for assessing the susceptibility of filamentous fungi.
AB  - The purpose of this study was to evaluate the Etest as an in vitro antifungal
      susceptibility test method for different moulds originating from human samples
      and from the environment. A total of 50 isolates (1 Acremonium, 18 Aspergillus, 2
      Cladosporium, 1 Epicoccum, 15 Penicillium, 2 Scopulariopsis and 11 Trichoderma
      strains) were tested by the Etest. Forty-six of the tested moulds (92%) were
      resistant to fluconazole with minimal inhibitory concentrations (MICs) > or = 256
      microg ml(-1). There were strains resistant to ketoconazole among Aspergillus
      niger, A. ochraceus and Cladosporium spp. with MICs > 32 microg ml(-1). For
      fluconazole, no differences were observed using two different inocula, while for
      itraconazole, ketoconazole and amphotericin B, a 1 or less step 2-fold dilution
      difference in MIC was seen for the most of 10 selected strains. The MICs of
      fluconazole and amphotericin B obtained for Trichoderma strains by the Etest and
      the agar dilution method were also compared. MICs for fluconazole were in
      agreement, while MICs for amphotericin B were higher with 1 or 2 steps of 2-fold
      dilutions for most of Trichoderma strains in the case of the agar dilution
      method.

PMID- 15571068
TI  - Production of extracellular proteases by human pathogenic Trichoderma
      longibrachiatum strains.
AB  - Species belonging to the filamentous fungal genus Trichoderma are well known as
      potential candidates for the biological control of plant pathogenic fungi and as
      cellulase producers of biotechnological importance. Several data were published
      in the last decade also about the clinical importance of this genus, indicating
      that Trichoderma strains may be potential opportunistic pathogens in
      immunocompromised patients. However, there is a lack of information about the
      potential virulence factors of clinical Trichoderma strains. This study was
      designed to examine the extracellular proteolytic enzymes of six clinical T.
      longibrachiatum isolates. Supernatants from induced liquid cultures of the
      examined strains were screened for proteolytic enzyme activities with 11
      different chromogenic p-nitroaniline substrates. The production of trypsin-like,
      chymotrypsin-like and chymoelastase-like protease activities cleaving N-Benzoyl-L
      Phe-L-Val-L-Arg-p-nitroanilide, N-Succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p
      nitroanilide, and N-Succinyl-L-Ala-L-Ala-L-Pro-L-Leu-p-nitroanilide,
      respectively, was common among the strains examined. Separation of trypsin- and
      chymotrypsin-like activities by column chromatography revealed, that both systems
      are complex consisting of several isoenzymes. The pH-dependence of these two
      protease systems was also studied. Based on the results, the different isoenzymes
      seem to have different optimal pH values. Extracellular proteolytic enzymes may
      be involved in the pathogenecity of Trichoderma strains as facultative human
      pathogens.

PMID- 15571069
TI  - Cloning, expression and purification of SmpB from Mycobacterium tuberculosis.
AB  - SmpB, a small tmRNA binding protein, is essential for trans-translation. 6His and
      FLAG tagged SmpB was cloned from Mycobacterium tuberculosis H37Rv. It was
      expressed in Escherichia coli using the T7 promoter-polymerase system. Anti-FLAG
      M2 agarose was used for its purification. Mycobacterial SmpB copurifies with
      other proteins. We identified elongation factor EF-Tu in the purified SmpB
      preparations.

PMID- 15571070
TI  - Innate immune functions of the keratinocytes. A review.
AB  - Human keratinocytes are known to kill living microbes. They express different
      pattern recognition receptors (PRRs) such as the Toll-like receptor 2 (TLR2),
      TLR4, the CD1d molecule and a keratinocyte mannose-binding receptor (KcMR). In
      response to challenge with microbes or microbial-derived substances the
      activation and nuclear translocation of NF-kappaB, the production of nitric oxide
      (NO) and inflammatory cytokines occur in keratinocytes, in a TLR-dependent
      manner. Blocking of NF-kappaB activation or NO production inhibit the Candida
      albicans-killing activity of keratinocytes. This Candida killing activity could
      be inhibited by blocking of KcMR. Recognition of invading pathogens in the
      epidermis triggers cytokine production in keratinocytes leading to elimination of
      pathogens and the activation of the adaptive immune system. These findings stress
      the importance of the role of keratinocytes in innate immunity.

PMID- 15571071
TI  - Helicobacter pylori-induced immunological responses in patients with duodenal
      ulcer and in patients with cardiomyopathies.
AB  - The interaction between the bacteria and the host is a key factor determining the
      clinical consequences of H. pylori infection. The immune system plays an
      important role in either promoting or preventing the disease. The mucosal
      production of TNF-alpha, IL-6, IL-8 and IL-10 and the CagA status were
      investigated in H. pylori-positive patients with duodenal ulcer (DU). The
      concentrations of these cytokines in gastric antral mucosal specimens from
      patients infected with H. pylori (n = 40) were determined by ELISA and compared
      with data on mucosal specimens from H. pylori-negative patients (n = 12). The
      local TNF-alpha, IL-6 and IL-8 concentrations in the antral biopsy samples were
      significantly higher (p < 0.001) in the patients infected with H. pylori than in
      the samples from the H. pylori-negative subjects. CagA positivity was
      demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H.
      pylori-positive (58 of 100) healthy blood donors. In complementary studies
      focusing on extragastric disease, it was found that 57% of patients with
      ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them
      had antibodies against human heat shock protein 60, too. This study suggests
      that, besides the bacterial virulence factor, the host response of an increased
      mucosal production of inflammatory cytokines can be relevant to the gastric
      pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart
      diseases the role of autoimmune processes induced by H. pylori cannot be
      excluded.

PMID- 15571072
TI  - Bacterial models for tumor development. Mini-review.
AB  - The tumor-inducing effects of Agrobacterium, Bartonella and Helicobacter
      bacterial species are compared step by step. An analogy for the existence of
      these individual steps is considered in connection with the development of
      cancer. The transformations of eukaryotic cells occur in particular in the type
      IV secretion system, i.e. involving the simultaneous transmission of DNA and
      protein from bacterial cells to eukaryotic cells. Thus, transfected cells
      facilitate the indefinite growth of tissue cells and additionally produce growth
      factors, triggering further bacterial multiplication. The higher numbers of
      bacteria then produce more transfection and the cycle repeats as long as the host
      lives. The main limiting factor is the frequency of bacterial infection, while
      the secondary rate-limiting factors are the levels of transforming growth factors
      and factors triggering bacteria growth. CONCLUSIONS: Analogous processes are
      probably responsible for the tumor induction by the three different bacterial
      species; however, the critical points for eradication are different. The early
      eradication or limitation of B. henselae or H. pylori can prevent hemangiomas,
      stomach cancer and malignant cell proliferation. The crown gall formation by A.
      tumefaciens can only be avoided by prevention of the transforming activity of a
      single bacterial infection. Questions arise as to what is common in the three
      processes, and the nature of the rate-limiting step in the three different
      models. The frequency of transformation is the rate-limiting step, but the co
      transmission of the DNA-protein complex is common in the three systems.

PMID- 15571073
TI  - Infectious plasmid resistance and efflux pump mediated resistance.
AB  - Various bacterial plasmids can be eliminated from bacterial species cultured as
      pure or mixed bacterial cultures by non-mutagenic heterocyclic compounds at
      subinhibitory concentrations. For plasmid curing, the replication should be
      inhibited at three different levels simultaneously: the intracellular replication
      of plasmid DNA, partition and intercellular transconjugal transfer. The
      antiplasmid action of the compounds depends on the chemical structure. The
      targets for antiplasmid compounds were analysed in detail. It was found that
      amplified extrachromosomal DNA in the superhelical state binds more drug
      molecules than does the linear or open-circular form of the plasmid or the
      chromosome, without stereospecificity which leads to functional inactivation of
      the extrachromosomal genetic code. Plasmid elimination also occurs in ecosystems
      containing numerous bacterial species simultaneously, but the elimination of
      antibiotic resistance-encoding plasmids from all individual cells of the
      population is never complete. The medical significance of plasmid elimination in
      vitro is, it provides a method to isolate plasmid-free bacteria for biotechnology
      without any risk of mutations, and it opens up a new perspective in rational drug
      design against bacterial plasmids. Hypothetically, the combination of antiplasmid
      drugs and antibiotics may improve the effectivity of antibiotics against
      resistant bacteria; therefore, the results cannot be exploited until the curing
      efficiency reaches 100%. Inhibition of the conjugational transfer of antibiotic
      resistance plasmids can be exploited to reduce the spreading of these plasmids in
      ecosystems.

PMID- 15571074
TI  - The antimotility action of a trifluoromethyl ketone on some gram-negative
      bacteria.
AB  - The inhibition of bacterial motility was studied by a trifluoro methyl ketone
      derivative on two Escherichia coli strains (wild strain having a proton pump
      system and the proton pump-deficient mutant strain) and two Helicobacter pylori
      strains (clarithromycin susceptible and clarithromycin resistant). Evidence is
      presented of the inhibitory action of 1-(2-benzoxazolyl)-3,3,3-trifluoro-2
      propanone (TF18) on the proton motive forces of the two bacterial strains by
      affecting the action of biological motor and proton efflux in the membranes. The
      swimming, the forward motion was more sensitive than the vibration or tumbling to
      the inhibition. We suppose that the inhibiton of bacterial motility is related to
      the virulence of bacteria: consequently the pathogenicity can be reduced in the
      presence of TF18.

PMID- 15571075
TI  - Therapy-induced antibodies against the antiviral and antiproliferative effects of
      interferons in patients with chronic hepatitis C virus infection.
AB  - Sera from 86 patients with chronic hepatitis C virus (HCV) infection treated with
      recombinant interferons-alpha (rIFN-alpha) were screened for IFN-binding and
      antiviral effect-neutralizing antibodies. Out of the 61 patients treated with
      rIFN-alpha2b, 46% had binding and 28% had neutralizing antibodies. 44% of the 25
      patients treated with rIFN-alpha2a developed binding antibodies and 24% had
      neutralizing antibodies. Contradictory data were observed concerning the
      appearance of anti-IFN antibodies and the outcome of IFN therapy. A significantly
      higher number of the patients with a sustained response to rIFN-alpha2b therapy
      formed antibodies than the number among the non-responder patients. At the same
      time, in the patients treated with rIFN-alpha2a, opposite data were found. The
      activity of the antibodies in some sera was studied against the antiproliferative
      effect of IFNs on Daudi cells by measuring the [3H]thymidine incorporation. The
      binding antibodies without neutralization of the antiviral effect of the IFNs
      inhibited the antiproliferative activity of the rIFNs, similarly to antibodies
      having both IFN-binding and antiviral effect-neutralizing capacities. At the same
      time, the antiproliferative effect of the natural IFN was less affected. It is
      suggested that the antiproliferative assay is more sensitive than the antiviral
      method for demonstration of the presence of antibodies exerting an inhibitory
      effect on the biological activities of IFN.

PMID- 15571076
TI  - Different staphylococcal strains elicit different levels of production of T
      helper 1-inducing cytokines.
AB  - Cytokine production has been implicated in the pathogenic mechanisms of
      infections caused by the staphylococci, since these bacteria may act as strong
      cytokine inducers. To gain deeper insight into the Th1 immune response activated
      by these bacteria, we have analyzed the interferon (IFN), interleukin-12 (IL-12)
      and IL-18-inducing activities of different Staphylococcus aureus (S. aureus), S.
      epidermidis and S. saprophyticus strains in human monocytes and murine bone
      marrow macrophages. A large majority of the S. aureus strains elicited the
      simultaneous production of IL-12 p70 and IFN-alpha in the human monocytes, while
      the S. epidermidis and S. saprophyticus strains induced only a low level of
      production, if any, of these cytokines. Furthermore, a majority of the S. aureus
      strains induced significantly higher IL-12 p70 and IL-18 titers in the murine
      bone marrow macrophages than did the S. epidermidis and S. saprophyticus strains.
      As IL-12, IL-18 and IFN-alpha stimulate Th1 differentiation synergistically, we
      suggest that S. aureus strains bias the immune response toward a Th1 phenotype,
      whereas S. epidermidis and S. saprophyticus strains provide a weaker stimulus for
      the production of Th1-inducing cytokines, and accordingly possibly elicit a less
      extensive Th1-associated adaptive immunity.

PMID- 15571077
TI  - A celebration of Horst Seidler on his sixtieth birthday.

PMID- 15571078
TI  - The diagnostic eye--on the history of genetic and racial assessment in pre-1938
      Austria.
AB  - The present contribution examines the history of the genetic biology experts
      reports in Austria up until 1938. This field of activity effected the research
      topics and -methods at the Viennese Institute for Anthropology considerably and
      caused an increase of application in practice. The motives of the scientists, the
      coalition of interests as well as the orientation towards the content of the
      discipline before 1938--which created the prerequisites for the racial experts
      reports of the NS time--will be discussed.

PMID- 15571079
TI  - Living with disabilities in Austria--with a special focus on the capital.
AB  - Life expectancy, especially in the older age groups, is growing enormously due to
      better social and medical care. According to published data on disabled people
      (1997), about 30 % of the total population (7,119,000) in Austria suffer from at
      least one physical disability. In this study, data from a micro census as well as
      a report from the Federal Ministry for Social Security and Generations is
      analyzed to illuminate the situation of impaired people with a focus on the
      capital Vienna. Among other results, it is anticipated that a large number of
      disabled people receive no help at all. About every 7th person regularly receives
      care, every 10th receives daily support. Care intensity increases with age
      showing a clear progression from the age of 60 onwards. 88% of the main
      supporting individuals are related to the handicapped person being supported.
      Women generally exhibit a much higher participation in nursing. The socio
      political developments are discussed.

PMID- 15571080
TI  - Recent paleoanthropological excavations of in situ deposits at Makapansgat, South
      Africa--a first report.
AB  - The Makapansgat Limeworks is a significant Pliocene site both for its sample of
      35 hominin fossils as well as its wealth of fossil fauna. The lithological and
      paleontological successions reveal local environmental changes that are important
      for understanding the context of hominin evolution in southern Africa. Yet most
      of the site's fossils were found in dumps left behind by quarry operations, and
      the paleoecological interpretations rest upon debatable assumptions about the
      original fossil provenience. We have recently initiated systematic
      paleoanthropological excavations at Makapansgat to recover well provenanced
      fossils in order to: 1) assess whether faunal successions are discernable in the
      Makapansgat sequence; 2) assist environmental interpretations of the site; 3) and
      potentially recover the oldest hominins in South Africa, roughly coincident with
      Australopithecus afarensis in East Africa. This paper presents a summary of our
      current paleoenvironmental research at the Limeworks and preliminary results of
      ongoing in situ excavations.

PMID- 15571081
TI  - Hominin brain evolution--new century, new directions.
AB  - The study of hominin brain evolution focuses on the interiors of fossilized
      braincases. Applications of recent three-dimensional computed tomography (CT) and
      magnetic resonance imaging (MRI) techniques for visualizing and measuring
      >>virtual endocasts<< from braincases in combination with advances in computer
      graphics and software for acquiring relevant data are transforming the way in
      which fossil skulls are analyzed, and improving the quality of paleoneurological
      investigations. Although CT imaging is preferred for fossil skulls, a novel
      method that combines high-resolution MRI of physical endocasts, electronic
      reconstruction of their missing parts, and warping of the resulting virtual
      endocasts is currently being developed and has great potential for future studies
      of hominin brain evolution. Applications of CT and MR techniques have already
      resulted in surprising new findings, which are briefly outlined. Exciting
      revelations about hominin brain evolution are expected as the 21st century
      unfolds.

PMID- 15571082
TI  - Early pliocene hominid tooth from Galili, Somali Region, Ethiopia.
AB  - A fossil hominid tooth was discovered during survey at Galili, Somali region,
      Ethiopia. The geological and faunal context indicate an Early Pliocene age. The
      specimen (GLL 33) consists of an almost complete lower right third molar likely
      representing a male individual of advanced age-at-death. Its comparative
      metrical, morphological and (micro)structural analysis (supported by a
      microtomographic record) suggests a tentative taxonomic allocation to
      Australopithecus cf A. afarensis.

PMID- 15571083
TI  - The dual origin of modern humanity.
AB  - Living Homo sapiens can define itself using both behavioral and anatomical
      uniquenesses. But is this possible when looking backward? Using a strict
      morphological definition, Homo sapiens can probably be traced back in the fossil
      record to about 150 kyr ago, which fits well with molecular estimates for the
      ancestor of all living human populations. However, activities reliably indicating
      established symbolic cognition can be recognized in the archaeological record
      only back to under 100 kyr ago. Since it is probable that the potential for
      symbolic cognition was born in the genetic/structural alterations that also gave
      rise to the distinctive morphological entity Homo sapiens, it appears that the
      expression of the human symbolic cognitive potential had to await, for many
      millennia, the >>discovery<< of that potential through a cultural rather than a
      biological stimulus. Most plausibly, this stimulus was the invention of language.
      Modern human symbolic cognition is not an extrapolation of pre-existing
      evolutionary trends, suggesting that Homo sapiens is not biologically >>fine
      tuned<< for any specific behavior patterns.

PMID- 15571084
TI  - Barking up the wrong ape--australopiths and the quest for chimpanzee characters
      in hominid fossils.
AB  - With the shift during the 1980s from a human-great ape ultimately to an orangutan
      (gorilla-(human-chimp)) theory of relatedness, the search for chimpanzee-like
      features in early hominids intensified. Reconstructions of early hominids became
      caricatures of chimpanzees, not only in soft tissue features (e.g. the nasal
      region), but in supposed bony structures (e.g. an anteriorly and especially
      superiorly protruding a supraorbital torus with a distinct posttoral sulcus
      behind). In spite of rampant >>Panophilia,<< actual morphologies of the majority
      of early hominid specimens are those cited as uniting an orangutan clade. Those
      specimens that are >>chimpanzee-like<< are probably not cladistically hominid.

PMID- 15571085
TI  - Matching lung volume data sets--a novel approach.
AB  - There is a significant demand in matching CT datasets of the lung. The increasing
      number of CT slices per examination due to the higher resolution of modern CT
      scanners and the need for quantification of the progress of disease and healing
      processes in follow-up studies. A volunteer's lung was scanned by the means of
      multidetector CT in two different states of ventilation. The necessary lung
      structures for the matching procedure like lung surface and branching points were
      segmented. A thin-plate spline method was used to calculate the matched lung
      volume. The preliminary results show an average error of 2 voxel, i.e. 2mm. The
      calculation of the transformation matrix takes about one second on a conventional
      PC, which is considerably faster than other methods described in literature. The
      method described may be apt to be introduced in radiological practice when it
      comes to compare high resolution CT scans in follow-up studies quantitatively.

PMID- 15571086
TI  - An >>Open Source<< Perspective of earliest hominid origins.
AB  - The >>Open Source<< Perspective deals with the spatio-temporal distribution
      pattern of Miocene hominids and suggests a pan-African perspective on the
      evolution of bipedalism. The shrinking of the rainforest from the Middle Miocene
      resulted in a selection pressure that was similar along its wide-stretched
      margin. The earliest hominids might represent co-existing geographic variants.

PMID- 15571087
TI  - Anthropology takes control of morphometrics.
AB  - There has been a startling change over the last decade in the intellectual
      context of morphometrics. In the 1990's, this field, which has not altered its
      focus upon the quantitative analysis of biomedical shape variation and shape
      change, was principally centered around concerns of medical image analysis; but
      now it is driven mainly by the demands of researchers in human variability,
      physical anthropology, primatology, and paleoanthropology instead. This essay
      celebrates that change and tries to account for it by reference to cognitive and
      intellectual aspects of the new home.

PMID- 15571088
TI  - Growth and malnutrition in Ethiopia.
AB  - This article focuses on anthropometric parameters as height for age, weight for
      age and weight for height, which are among the most used tools for assessing well
      being of infants and children. Such data have been collected between 1992--1993
      from samples of infants and children aged between 2 and 10 years from urban and
      rural areas of Ethiopia. Similar to many other reports from developing countries
      the great amount of malnourished children is preoccupying as reflected by about
      15% of children below the 5th centile of weight for height and about 53% of
      children below the 5th centile of height for age and about 45% below the 5th
      centile of weight for age.

PMID- 15571089
TI  - Artificial mummies from the Andes.
AB  - In 1997 agricultural workers, turned into looters, found an intact funerary site
      in the cloud forest in northeastern Peru. A prompt archaeological rescue project
      permitted the recovery of an important collection of mummies and artifacts that
      are providing important insights about the archaeology of the Chachapoya people
      that established in this area around 900 AD up to the Inca conquest of this
      territory around the year 1475. The mummies recovered showed evidence of cultural
      practices devised and used to assure the preservation of the human bodies. Such
      practices are also reported for among Chinchorro and Chiribaya mummies in the
      Andes. A cultural interpretation of these funerary activities is discussed
      connecting the practice of the cult to the ancestors to the access and management
      of resources and territory.

PMID- 15571090
TI  - The representation of self reported affect in body posture and body posture
      simulation.
AB  - It is taken for granted that the non-verbal information we acquire from a
      person's body posture and position affects our perception of others. However, to
      date human postures have never been described on an empirical level. This study
      is the first approach to tackle the unexplored topic of human postures. We
      combined two approaches: traditional behavior observation and modern
      anthropometric analysis. Photographs of 100 participants were taken, their body
      postures were transferred to a three dimensional virtual environment and the
      occurring body angles were measured. The participants were asked to fill in a
      questionnaire about their current affective state. A principal component analysis
      with the items of the affect questionnaire (Positive Negative Affect Scales,
      PANAS) revealed five main factors: aversion, openness, irritation, happiness, and
      self-confidence. The body angles were then regressed on these factors and the
      respective postures were reconstructed within a virtual environment. 50 different
      subjects rated the reconstructed postures from the positive and negative end of
      the regression. We found the ratings to be valid and accurate in respect to the
      five factors.

PMID- 15571091
TI  - Socioecological aspects of human reproduction in Sub-Saharan Africa.
AB  - The purpose of this study was to compare fertility outcome of two populations of
      northern Namibia, following different ways of subsistence. The total number of
      offspring, but also the number of dead and surviving offspring was compared
      between 236 !Kung San (91 females, 145 males) hunter gatherers and 248 Kavango
      (87 females, 161 males) horticultural pastoralists and a small number of Kavango
      people living in the urban center of Rundu. While no typical differences in
      fertility outcome between the study populations could be observed in males,
      marked differences were found for the female sample. As to be expected
      traditional Kavango women had given birth to a higher number of children and
      these children had a higher chance to survive in comparison to those of !Kung San
      women. On the other hand Kavango females living in urban centers reported a
      significantly lower number of offspring. It can be concluded that even in recent
      populations fertility differences according to subsistence patterns are
      observable.

PMID- 15571092
TI  - Group members' assessment of their conductor in small analytic group.
AB  - In this pilot study the authors present the group members' assessment of their
      conductor in group analysis--the treatment conducted in accordance with concept
      >>group-as-a-whole<< of S. H. Foulkes. There will be presented the results
      obtained by scale for evaluation of characteristics of the group therapist. In
      the scale, developed by the authors of the study, there were 30 items and by
      factorial analysis it gave three interpretable factors: authenticity, empathy and
      distrust. By self-evaluation the members of three small groups, i.e. 20 patients,
      ranked characteristics of their conductor. The patients, assessing the degree of
      their accordance with 30 items of the evaluation scale, expressed whether and how
      much they experienced their conductor as an authentic, empathic and trustworthy
      person. While in the beginning of the group analytic process the conductor's role
      was important, his importance decreased as the group-as-a-whole developed. Group
      experience became more important than the conductor. In other words, the group
      itself became the therapist, what is one more the proof of the Foulkes' concept
      of >>the group-as-a-whole<<.

PMID- 15571093
TI  - Differences in sexual functioning between patients with benign and malignant
      breast tumors.
AB  - The aim of this study was to compare differences in sexual behavior between
      patients with benign and malignant breast tumors. A total of 187 patients treated
      for breast tumors (benign or malignant) at the General Hospital >>Pozega<<,
      Croatia, filled in the questionnaire between January 2001 and May 2003. Patients
      were asked to fill in the questionnaire one to ten years after treatment of
      breast tumor, while they were on their regular control visit. Deterioration in
      sexual life experienced 36.27% of patients with benign tumors and 51.76% of
      patients with malignant tumor (p<0.01). The main reason of sex life impairment in
      both groups was distortion of body image perception. Most of partners did not
      change their behavior toward women with breast tumors (48.72% for benign group
      and 41.82% or malignant group, p>0.05). A great amount of women in both groups
      felt certain change in her >>body image<<, but in greater extent in malignant
      group (41.18% vs. 25.49%), (p<0.05). From our results we can see that patients in
      this study do not recognize need for consultation with their physician regarding
      sex life after treatment of tumor (41.18% for benign and 35.29% in malignant
      group). It can be concluded that considerable amount of attention should be given
      to psychological aspects of recovery which can improve prognosis and quality of
      life in general.

PMID- 15571094
TI  - >>For better or worse, till death us do part<<--spousal age gap and differential
      longevity: evidence from historical demography.
AB  - Based on a set of 2,371 family related entries dating from 1688 to 1921, the
      current study tried to verify longevity differentials due to interspousal age
      difference. For the purpose of the analysis, age-heterogamy was operationalized
      in terms of sample-specific marital age gap (3.2 years) with a standard deviation
      of 6.1 years. Based on this, five marriage groups were isolated. Female mean age
      at marriage experienced a slight increase over time, while the male mean at
      marriage decreased. This led to an appreciable narrowing of the spousal age gap.
      Age-homogamous unions were most prevalent in the lower socio-economic class (day
      laborers, industrial workers) (p<0.01). In both husband-older and wife-older
      unions, the interspousal gap increased with marriage order. In accord with
      previous studies, mean age at death varied significantly by marriage group.
      Females, who married younger men, died later than females, who married older men.
      In contrast, male longevity was most depressed within age-similar marriages,
      while those who married older or younger wives displayed higher life spans.
      Overall, marriage to a younger spouse seemed to increase longevity prospects
      (p<0.05). These differentials were not exclusively a function of the marital age
      gap, but were affected by diverse confounders such as reproductive output and
      socio-economic status.

PMID- 15571095
TI  - Morphological characteristics of the acetabulum.
AB  - The aim of this research was to accurately measure the surface of the semi lunar
      articular surface of the pelvis (facies lunata acetabuli) and the variability of
      the acetabular geometry, as well as to determine the correlation between measured
      parameters. 30 macerated anatomical specimens of pelvic bones were measured. The
      radius and depth were measured in the classical way, while cartilaginous surface
      area was measured using small fragments of measuring paper to avoid errors in
      measurement due to the curvature of the surface. Computerized calculations
      provided accurate surface values. In our research, facies lunata acetabuli
      measured 2294+/-329 mm2. Diameter of the opening of the acetabulum measured
      25.8+/-1.9 mm. Acetabular depth was 30+/-3.2 mm. Correlations between the surface
      area of the facies lunata acetabuli and the radius of the acetabular opening
      curvature (r=0.71), surface area of the facies lunata acetabuli and the depth of
      the acetabulum (r=0.80) and the radius of the acetabular opening curvature and
      the depth of the acetabulum (r=0.80) were confirmed. For precise assessment of
      the facies lunata acetabuli surface area, the simplest and the cheapest method is
      the method of measurement using small fragments of measuring paper and software
      analysis. There is a significant correlation between the depth, opening of the
      acetabulum and surface area of the facies lunata.

PMID- 15571096
TI  - B-mode and color Doppler ultrasound of the forearm arteries in the preoperative
      screening prior to coronary artery bypass grafting.
AB  - The objective of this paper was to establish the normal findings of B-mode and
      color Doppler ultrasound of the forearm arteries in candidates for coronary
      artery bypass grafting with radial artery graft. Examination of radial and ulnar
      arteries was performed in 127 patients. The vessel diameters and peak systolic
      velocities were measured and the presence of atherosclerotic changes,
      calcifications and anatomical variants was assessed. Radial artery proved to be
      dominant forearm artery with non-significant side-to-side asymmetry. The luminal
      changes were present in 30% of the patients. Ulnar arteries were more prone to
      these changes than radial arteries (28.4% vs. 24.4%). The anatomical variants
      found included ulnar artery hypoplasia in 3.9% of patients and high brachial
      artery bifurcation in 2.4% of patients. No cases of high-grade stenosis or
      occlusion were found. The results of the present study indicate that B-mode and
      color Doppler are valuable methods for preoperative screening as they enable
      morphological and functional evaluation of the forearm circulation.

PMID- 15571097
TI  - The results after transrectal prostate biopsy with 12 biopsy cores taken.
AB  - This report describes the clinical value of transrectal prostate biopsy during
      which 12 biopsy cores are taken in comparison to the classical sextant method.
      There were 106 patients included in the study, who had transrectal prostate
      biopsy (TRB) due to abnormal finding after digitorectal examination (DRE) and/or
      values of PSA > 4 ng/ml in the period from 4 October 2001 till 14 August 2002.
      There were 117 biopsies with 12 biopsy cores taken, 6 cores from each lobe.
      Prostate cancer was confirmed in 49 patients (46%). Out of total number of
      confirmed cancer cases, initial biopsy detected 94%. There were three patients
      who had suspicious DRE finding, with PSA value of < 4 ng/ml, but cancer was not
      detected in any of them. In the patient group with PSA value between 4-10 ng/ml,
      cancer was detected in 26% of them and in the group with PSA value > 10 ng/ml
      cancer was detected in 58%. The most common Gleason score in the case of cancer
      was 7 (43%). During the biopsy procedure, 3 patients experienced strong vasovagal
      reactions, meaning that out of 117 biopsies incidence of complications was 2.6%.
      Few days after the biopsy, two patients developed urogenital tract infections
      (1.7%) and right after the procedure, there was one case of strong hematuria
      (0.8%) and strong rectal bleeding (0,8%) that needed hospitalization. Our results
      regarding the incidence of complications do not differ much from the results in
      the literature. According to data in the literature regarding sextant biopsy, 15
      34% of cancer cases remain undiagnosed at initial biopsy. The method of 12 biopsy
      cores fails to diagnose only 6% of all cancers, but it is important to note that
      in the mentioned period, re-biopsy was indicated only in 11 from 60 patients with
      negative biopsies.

PMID- 15571098
TI  - Gender differences in cardiovascular diseases risk for physical education
      teachers.
AB  - The aim of the study was to evaluate the level of habitual physical activity in
      Croatian physical education (PE) teachers, as well as the existence of some other
      risk factors for the development of cardiovascular diseases (CVD). The sample
      consisted of 191 PE teachers aged 24 to 59 years (122 men, mean age 42.6+/-8.76
      and 69 women, mean age 40.3+/-8.84;p=0.09). In order to assess the level of
      habitual physical activity, the teachers were asked to fill in Baecke's
      questionnaire. The questionnaire comprises 16 items testing physical loads at
      work, during sport activity and during leisure time. The questionnaire also
      contains 8 items, each of them representing a certain cardiovascular risk factor.
      In comparison to average adult employed population, PE teachers have a
      significantly higher level of sport and leisure time activity, which could have a
      favorable impact on the incidence of particular risk factors, such as
      overweight/obesity, systolic hypertension and blood cholesterol level. This is
      more obvious in females PE teachers who pay more attention to the principles of
      healthy life style: optimal body weight regulation, low fat diet and higher
      amount of leisure time physical activity (significantly higher than in male
      teachers). Female PE teachers who have maintained their active life style
      decrease the risk of CVD, particularly after the age of 55. Although it is
      necessary to keep in mind all the limitations of a questionnaire study, this
      preliminary report leads to the conclusion that male PE teachers, although
      physically active at job, have still kept sedentary habits, often have maintained
      heavy smoking habits, are slightly overweight, thus minimizing the positive
      effects of their demanding workplace. Consequently, average male PE teachers'
      risk for CVD development corresponds to the risk of general male population.

PMID- 15571099
TI  - Dental evidence of exhumed human remains from the 1991 war in Croatia.
AB  - The aim of this paper is to present the post mortem dental evidence and dental
      health of the victims exhumed throughout the territories of Croatia that was
      temporarily occupied during the war. A total number of 62,432 teeth out of 1,253
      human bodies exhumed from 5 different counties were analyzed. The majority of
      victims inhabited those areas before 1991. Post mortem dental characteristics
      were analyzed according to the American Board of Forensic Odontology and WHO
      methodology. The results show the highest level of the dental health before 1991
      in the Vukovarsko-Srijemska County. The decayed (D), missing (M), filling (F),
      teeth (T), DMFT of that County was at the lowest level i.e. at 5.2. In all of the
      other counties, it was always between 6 and 12. The material most frequently used
      for the dental fillings was amalgam. Its highest frequency level was recorded in
      the County 4 (8%) and lowest in the County 1 (1.5%), p<0.001. The most frequent
      prosthodontic appliances were acrylic dentures. Their frequency was lowest in the
      County 5 (1.3%) and highest in the County 3 (11.6%), p<0.001. Determination of
      sex and dental age showed that victims were mostly men (79%) of middle and
      elderly age (89%). Teeth were useful also for monitoring of the quality of
      exhumations--taking into consideration number of empty dental sockets. The
      highest number of empty dental sockets was recorded in the County 3 (40.4%) and
      lowest in the County 1 (13.5%), p<0.001. Even after many years in the soil, teeth
      proved to be the most preserved human organs and valuable indicators of identity
      as well as of the way of life before death.

PMID- 15571100
TI  - Intercostal variation for age estimation--are the standards for the right 4th rib
      applicable for other ribs?
AB  - Age estimation of unknown skeletal remains is very important in forensic
      medicine. Morphologic methods are fast and easy to use for purpose of age
      determination. The sternal ends of the ribs are a reliable method of age
      estimation from late adolescence to old age. Iscan et al developed a phase
      analysis method for the right 4th rib that was sex and race specific. The purpose
      of this study is to determine the accuracy of the standards of age estimation
      from the right 4th and other rib using the phase analysis for the Turkish
      population. The sample consisted of right and left 3rd, 4th and 5th ribs from 34
      Turkish women and 76 men. There were statistically significant variations found
      on the right 5th, left 3rd, 4th, and 5th ribs according to these standards in men
      for phases 5, 6, and 7. For women, all the right and left ribs included in this
      study were in concordance with right 4th rib standards in all phases.

PMID- 15571101
TI  - Two cases of joint disease in post-medieval church cemetery of St. Ilija.
AB  - Evidence of disease was analyzed from the skeletal remains of 11 individuals
      dating to the post-Medieval period from church cemetery of St. Ilija in Serbia.
      Two individuals showed pathological condition affecting joints. It was supposed
      that first individual had been suffering from Legg-Calve-Perthes disease. It
      seems that this condition remained untreated, with extensive bone remodeling, and
      that the deformity of femoral head and acetabulum caused secondary degenerative
      joint disease at a relatively early age of this individual. Second case was
      related to the bony akylosis of the hand finger, probably caused by Dupuytren's
      disease. In addition, we discussed development of differential diagnosis in both
      pathological conditions.

PMID- 15571102
TI  - Copy number of DAZ genes in Slovenian and Bosnian general population.
AB  - Deletions of two of four DAZ (Deleted in AZoospermia) gene copies located on the
      Y chromosome were associated with spermatogenic failure, but the information on
      DAZ copy number is still very scarce. The aim of this study was to determine the
      frequency of partial DAZ gene deletions and to analyze the existence of
      duplications in general Slovenian and Bosnian population. To answer these
      questions, we used real time PCR. We analyzed 100 male samples from Slovenian and
      Bosnian general population. The incidence of two DAZ gene copies was 6% (3/50) in
      Slovenian population. The incidence of more than four DAZ genes was 2% (1/50) in
      Slovenian population and 8% (4/50) in Bosnian population. Observed differences
      have not reached statistical significance. In conclusion we demonstrate that DAZ
      genes are not only prone to deletions but also to duplication events. Further
      studies are needed to estimate the prevalence of these mutations and its'
      relevance to male infertility.

PMID- 15571103
TI  - Population genetic studies of the pancreatic amylase (AMY2, E.C. 3.2.1.1) in
      Bulgaria.
AB  - The pancreatic amylase (AMY2, E.C. 3.2.1.1) polymorphism has been studied in 2346
      individuals from south-central and south-eastern Bulgaria. The allele frequencies
      have been determined as AMY2*1 = 0.9520 and AMY2*2 = 0.0480. The neighbor joining
      tree of seven subpopulations revealed only small genetic distances. Compared with
      other populations, the Bulgarian sample clustered with samples from Romania,
      Hungary, Germany and Switzerland, with larger distances to Albania, Greece and
      Macedonia.

PMID- 15571104
TI  - Cholinesterase unit establishment and issuing of >>Warning Cards<< for carriers
      of suxamethonium sensitive serum butyrylcholinesterase variants.
AB  - Recognition of butyrylcholinesterase (EC 3.1.1.8) variants in human serum is
      essential to identify patients who may be susceptible to a prolonged reaction of
      suxamethonium and mivacurium, short-acting muscle relaxants. Thus they can be
      given appropriate advice along with their relatives who may be similarly
      affected. Therefore, Cholinesterase Unit for detection of individuals, carriers
      of inherited suxamethonium sensitive butyrylcholinesterase variants was
      established at the Institute for Clinical Chemistry of the Clinical Hospital
      >>Merkur<<, Zagreb, Croatia. A study was conducted on sera from patients referred
      to the Unit. Butyrylcholinesterase variants were determined by measuring the
      enzyme activity and inhibition by specific inhibitors in the sera of 384 patients
      and of the members of seven families. Cholinesterase Unit issued >>Warning
      Cards<< to the carriers of inherited serum butyrylcholinesterase variants in
      order to avoid prolonged apnea that suxamethonium might cause.

PMID- 15571105
TI  - The significance of salivary and serum interleukin 6 and basic fibroblast growth
      factor levels in patients with Sjogren's syndrome.
AB  - Role of various cytokines have been implicated in the development and
      perpetuation of Sjogren's syndrome (SS), but no specific cytokine could be
      determined as a major contributor to the SS. Salivary and serum interleukin 6 (IL
      6) levels have been studied previously in patients with SS, but data upon
      salivary and serum basic fibroblast growth factor (bFGF) in SS are lacking. The
      aim of this study was to evaluate levels of salivary and serum IL-6 and bFGF in
      18 patients with SS, age range 32-79, mean 54.05 years. Control group consisted
      of 23 healthy participants, mean age 25 years. Serum IL-6 and bFGF levels were
      not significantly different between patients with SS and healthy controls.
      Elevated levels of salivary IL-6 and bFGF in patients with SS when compared to
      the healthy controls were found (p<0.001). We might speculate that higher levels
      of salivary IL-6 and bFGF in patients with SS might originate from local
      production probably having source in the salivary glands.

PMID- 15571106
TI  - Inbreeding effects on metrical phenotypes among North Indian Children.
AB  - This study aimed to examine the effects of inbreeding on 12 quantitative
      phenotypes like body weight, height, sitting height, head circumference, head
      length, head breadth, chest circumference, verbal, performance and full scale
      intelligence quotients, systolic and diastolic blood pressures among North Indian
      Children. The sample consisted of 3,253 subjects (1,683 males and 1,570 females)
      including offspring of first cousins, first cousins once removed, second cousins,
      (inbred part of samples) and unrelated spouses (non-inbred part of samples)
      ranging in age from 6 to 14 years from the Aligarh district, Uttar Pradesh in
      North India. Samples were selected purposively to estimate the average inbreeding
      coefficients based on 3 ancestral generations and using Wright's path method. The
      average inbreeding coefficient of the present inbred part of sample is 0.04609.
      The mean ages of males and females were almost equal for both inbred and non
      inbred individuals. A significant reduction of means (p < 0.05) or inbreeding
      depression has been observed in inbred series for all anthropometric and
      psychometric traits for both the sexes. A significant elevation of mean with
      inbreeding is observed for systolic and diastolic blood pressure. The average
      inbreeding depression per 10% inbreeding appeared very high in verbal IQ (> or
      =23), performance IQ (> or =40), full scale IQ (> or =28), systolic blood
      pressure (> or =10) and diastolic blood pressure (> or =12) among both sexes. On
      the whole, relatively greater amount of inbreeding effects are apparent among all
      measures of intelligence quotient and blood pressures compared to the
      anthropometric traits. The results of the present work have thrown light on the
      nature and mechanism of genetic effects of inbreeding on certain quantitative
      traits in human.

PMID- 15571107
TI  - Holistic anthropological research of Hvar Islanders, Croatia--from parish
      registries to DNA studies in 33 years.
AB  - The complexity of interactions between hereditary, environmental and cultural
      factors in determining human phenotypes is often underestimated in biomedical
      research. In this paper, we present 33 years of holistic anthropological research
      that was being conducted since 1971 in the island of Hvar, Croatia. During this
      period, detailed characterization of migrations, demography, isonymy, linguistic
      differences, anthropometric traits (head and body dimensions), physiological
      (cardio-respiratory) properties, quantitative and qualitative dermatoglyphic
      traits, radiogrammetric metacarpal bone dimensions and genetic traits (classical
      antigens, HLA diversity, DNA short tandem repeat -STR, mitochondrial DNA and Y
      chromosome polymorphisms) was performed. The analysis of this large collection of
      data using both model-bound and model-free approaches showed that the complexity
      underlying human biological traits may be considerably greater than generally
      assumed, which has important implications for design of future studies into
      genetic determinants of complex traits.

PMID- 15571108
TI  - Health of returnees in Osijek Region and required special measures of health care
      and community organization.
AB  - Many citizens from the Osijek-Baranja County, in order to survive, left their
      homes during the 1991/92 war in Croatia and spent between 5 and 7 years in exile.
      The aim of this pilot research was to assess the health status (physical, mental
      and social) of refugee /returnee population and their use of health services, to
      identify the factors influencing their adaptation, and to propose the health
      programs, psychological and social support, which could help foster integration
      into the social and community life, education and employment. The study was done
      on a randomized sample of 589 respondents using the 2003 Croatian Health Survey
      with an additional questionnaire related to the problems of returnees. The
      results of the study show good organization of health service in returnees'
      communities, with exception of gynecological and dental services. There was also
      a presence of health transportation problem and the problem in the supply of
      medicines. Finally, the results show that the returnees' communities were
      dominated by social problems such as lack of employment, lack of support for
      elderly, poverty, and concerns for children's prospects. This implies the
      necessity for intervention in both mental and social aspects. Measures to be
      undertaken in the next stage of the Project will be aimed at the work in the
      refugee communities and based on public health working methods such as
      organization of the community by stimulating intergenerational solidarity,
      education and raising awareness of self-help.

PMID- 15571109
TI  - Integration of aerobic power into the morphological-motor system in children aged
      7-11 years.
AB  - The aim of the study was to analyze integration of aerobic power into other
      dimensions evaluated. For this purpose, predictor relations of the morphological
      motor variables were analyzed with a 3-minute run as a criterion (according to
      school grade and sex). Four morphological and 6 motor variables covering the
      morphological-motor system were used in a sample of 4,440 children of both sexes
      aged 7-11 years, elementary school first- to four-graders from the Primorje
      Gorski Kotar County, Republic of Croatia, divided into 8 groups. Data were
      processed by use of regression analysis. Study results clearly showed the values
      of the criterion variable to rise and criterion prediction using the set of
      predictor variables to improve with age. Also, the number of predictors included
      in power run prediction was observed to significantly increase with age. Strength
      factors with a predominance of explosive strength and repetitive strength in boys
      and girls, respectively, were the best criterion predictors. It is emphasized
      that development of the morphological-motor system and thus functioning of the
      body as a whole are influenced by aerobic power upgrading. Appropriate systematic
      kinesiologic activities accelerate the process of aerobic power integration in
      the morphological-motor system. As indicated by study results, this integration
      occurred at a faster rate and was more intensive in girls than in boys.

PMID- 15571110
TI  - A model in environmental training--The University / Elementary School /
      Municipality Cooperation.
AB  - This study targets development of an effective training scheme model that can be
      implemented at elementary school level with focus on recovery and recycling of
      wasted papers in Turkey. For this purpose, three schools were chosen from a
      district within Istanbul. They were separated from one another as full
      intervention (FI), semi-intervention (SI) and control (C) schools. Different
      levels of educational activities carried out in the schools, mostly in the FI
      school, were directed toward being informative as regards recycling and the
      development of a positive attitude. Afterwards, in order to evaluate the effects
      of the training, paper wastes were collected in recycle bins placed at
      appropriate points in schools and weighed on a weekly basis. Quite a significant
      result was found (p = 0.0001), when the difference was calculated through the
      Kruskal Wallis Variance Analysis method, regarding the weekly average amount of
      paper in each of the three schools against per person. Furthermore, when the
      results were evaluated and compared as to the ones before the 2.5 months summer
      vacation and the ones after it, the seven measurements taken before (p = 0.001)
      and the eight taken afterwards (p = 0.0001), were found to have valid
      differences, once again, as against schools. The results show that the approach
      we provided to education is an effective method not only for the collection of
      paper wastes but also for applications in various areas of health education.

PMID- 15571111
TI  - Neandertals...150 years later.
AB  - The place of Neandertals in modern human emergence has been a subject of debate
      since the first recognized Neandertal skeleton was discovered in 1856. This paper
      presents an overview of morphological, archaeological, and genetic evidence
      commonly used in discussions of Neandertals and their evolutionary significance.
      A brief historical sketch of the argument provides insight into the changing
      views on these interesting people. The major models proposed to explain modern
      human origins are also discussed.

PMID- 15571112
TI  - The impact of in-vehicle cell-phone use on accidents or near-accidents among
      college students.
AB  - With in-vehicle use of cell phones rapidly increasing, the safety of young
      drivers, who represent 14% of licensed drivers but 26% of drivers involved in
      fatal crashes, may be disproportionately threatened. The authors used a
      questionnaire to examine the association between in-vehicle cell-phone use and
      accidents or near-accidents among 1,291 conveniently recruited college students
      in 4 states. Of the 1,185 respondents who were drivers, 87% had a cell phone, and
      86% of the cell-phone owners reported talking while driving at least
      occasionally. Of the 762 reported accidents or near-accidents, 21% (n = 159)
      involved at least 1 of the drivers talking while driving. Chi-square tests and
      logistic regression analyses showed that the frequency, not the duration, of
      drivers talking while driving was related to experiencing accidents or near
      accidents. Differences between drivers who used cell phones and nonusers in
      unsafe driving behaviors and attitudes were also examined, and target groups for
      intervention efforts against talking on a cell phone while driving are suggested.

PMID- 15571113
TI  - Human immunodeficiency virus (HIV) testing and false disclosures in heterosexual
      college students.
AB  - The authors assessed factors that motivate individuals to report negative human
      immunodeficiency virus (HIV) antibody test results, although they had never been
      tested. In particular, they investigated sexual intimacy motives associated with
      the needs for affiliation, sex, and dominance as contributing factors for faulty
      disclosures. Participants were 246 sexually active heterosexual students.
      Overall, 21% of the sample had been tested for HIV, and most individuals
      disclosed their results to intimate partners. Of the entire sample, 5% had
      previously told an intimate sexual partner they were HIV-negative, although they
      had not been tested. HIV testing and perceptions of partner deceptions with
      reference to primary prevention efforts and applications are explored.

PMID- 15571114
TI  - Healthcare providers' treatment of college smokers.
AB  - About 28% of college students smoke tobacco, and many will continue smoking into
      adulthood. Although little is known about how to help college students quit
      smoking, 1 promising strategy is healthcare providers' advice. To estimate their
      life-time receipt of brief advice and to identify characteristics that predict
      who may receive that advice, 348 college students completed a survey about their
      smoking and related practices. Seventy-seven percent of the smokers (73% of the
      students) were asked about smoking. Of those smokers, 57% were advised to quit,
      22% were given advice about quitting, 5% were helped with setting a quit date,
      and 4% were offered follow-up. Occasional smokers were less likely than daily
      smokers to be advised to quit. Although 36.2% of the smokers did not report their
      smoking accurately, smokers who were accurate were more likely to be advised to
      quit and to be given advice about quitting.

PMID- 15571115
TI  - Differences in health determinants between international and domestic students at
      a German university.
AB  - The authors used a standardized questionnaire to survey 201 international and 193
      German students at the University of Bielefeld, Germany, to determine differences
      in health practices between the 2 groups and to identify targets for health
      promoting interventions. Multivariate logistic regression models revealed that
      long-term female international students (those whose duration of residency in
      Germany was more than 2 years) had lower levels of physical activity and alcohol
      consumption than their German counterparts and higher rates of smoking
      independently associated with international citizenship. Short-term international
      female students were less likely than German students to receive social support.
      Among men, long-term international student status was associated with daily
      smoking and inconsistent seat belt use, whereas short-term student status was
      associated with a lower rate of seat belt use, a higher level of perceived
      stress, and a healthier diet, compared with domestic students. Findings from the
      study could give rise to health-promotion activities for international students
      at German universities; additional studies at other European universities are
      necessary before making further recommendations.

PMID- 15571116
TI  - Binge drinking in female college students: the association of physical activity,
      weight concern, and depressive symptoms.
AB  - As an initial step in building gender-specific binge drinking intervention
      programs, the authors investigated the relation of potentially modifiable factors
      (physical activity level, weight concern, and depressive symptoms) to binge
      drinking while controlling for the effects of previously established correlates
      of binge drinking (tobacco and marijuana use, GPA, and perception of peer alcohol
      use). Four-hundred-twelve college women completed an in-class survey.
      Multivariate analyses revealed that tobacco and marijuana use, GPA, and physical
      activity were significantly associated with binge drinking, whereas tobacco use
      and perception of peers' alcohol use were associated with more frequent binge
      drinking. The findings suggested that the variables associated with any binge
      drinking and frequency of binge drinking may differ and that binge drinking can
      be associated with positive health behaviors (ie, greater physical activity) as
      well as risky health behaviors (eg, tobacco use).

PMID- 15571117
TI  - Bibliography: Julian Hoff, M.D.

PMID- 15571118
TI  - 2003 Congress of Neurological Surgeons presidential address. The value of
      neurosurgery.

PMID- 15571119
TI  - Microsurgical anatomy and neurosurgical pathology.

PMID- 15571120
TI  - The fundamentals of patient assessment: the importance of the examination and the
      patient relationship.

PMID- 15571121
TI  - Biomechanics of spinal deformity correction.

PMID- 15571122
TI  - Neurosurgical continuing medical education.

PMID- 15571123
TI  - ThinkFirst: fundamentals of injury prevention.

PMID- 15571124
TI  - The fundamentals of building an effective neurosurgical practice.

PMID- 15571125
TI  - Management of the Chiari malformation and spinal dysraphism.

PMID- 15571126
TI  - The neurosurgeon as clinician-scientist: the fundamentals.

PMID- 15571127
TI  - Maintenance of certification: a fundamental component of contemporary
      neurosurgical practice.

PMID- 15571128
TI  - Honored guest presentation: fundamentals of neurosurgical practice.

PMID- 15571129
TI  - Foundations of neurological surgery: the state of the journal and documentation
      of surgical methods.

PMID- 15571130
TI  - Biologic warfare for a good cause: HSV-1 anti-tumor therapy.

PMID- 15571131
TI  - Molecular characterization of brain tumors.

PMID- 15571132
TI  - The science of sports medicine.

PMID- 15571133
TI  - Promethazine: a novel application as a neuroprotectant that reduces ischemia
      mediated injury by inhibiting mitochondrial dysfunction.

PMID- 15571134
TI  - Honored guest presentation: scientific foundations of clinical neurosurgery.

PMID- 15571135
TI  - Mediators of blood-brain barrier disruption and potential therapeutic
      interventions for protection of the barrier following focal ischemia.

PMID- 15571136
TI  - Wrong science: the SPORT trial and its potential impact on neurosurgery.

PMID- 15571137
TI  - Bad science ISAT: the impact on neurosurgical practice.

PMID- 15571138
TI  - Cellular immunity in the treatment of brain tumors.

PMID- 15571139
TI  - What genes can teach us about human cerebrovascular malformations.

PMID- 15571140
TI  - Fetal surgery for myelomeningocele.

PMID- 15571141
TI  - Database systems for research in clinical practice management.

PMID- 15571142
TI  - Advances in the surgical management of epilepsy.

PMID- 15571143
TI  - Innovations in surgical approach: the marriage of technique, technology, and
      judgment.

PMID- 15571144
TI  - Neuroendoscopy: present and future applications.

PMID- 15571145
TI  - Novel spinal fixation.

PMID- 15571146
TI  - Translational research strategies applied to glioma therapeutics.

PMID- 15571147
TI  - Repairing the damaged spinal cord: from stem cells to activity-based restoration
      therapies.

PMID- 15571148
TI  - The operating room of the future.

PMID- 15571149
TI  - Controversies in the surgical management of Chiari I malformations: what is the
      surgical procedure of choice? To open dura or not to open dura?

PMID- 15571150
TI  - Controversy: brain metastases: "ideal treatment"? Part I: Moderator overview.

PMID- 15571151
TI  - Part II: Surgery versus radiosurgery for brain metastasis: surgical advantages
      and radiosurgical myths.

PMID- 15571152
TI  - Part III: Radiosurgery in the treatment of brain metastases.

PMID- 15571153
TI  - Special lecture: Brain stimulation: perspectives for the future.

PMID- 15571154
TI  - Update on the brain attack coalition.

PMID- 15571155
TI  - Discogenic back pain: the case for surgery.

PMID- 15571156
TI  - Part I: Clip versus coil: options in the management of ruptured intracranial
      aneurysms.

PMID- 15571157
TI  - Part II: Ruptured intracranial aneurysms: the case for clipping.

PMID- 15571158
TI  - Surgical treatment of Parkinson's disease: deep brain stimulation versus
      radiofrequency ablation.

PMID- 15571159
TI  - Stereotactic and Functional Neurosurgery Resident Award: Responses of subthalamic
      neurons during visually guided movements in patients with Parkinson disease.

PMID- 15571160
TI  - Synthes Award for Resident Research in Spinal Cord & Spinal Column Injury:
      Surgical repair of the injured spinal cord using biodegradable polymer implants
      to facilitate axon regeneration.

PMID- 15571161
TI  - Synthes Award for Resident Research in Spinal Cord & Spinal Column Injury:
      Statins for the treatment of neurological injury: a role beyond cholesterol
      lowering.

PMID- 15571162
TI  - Council of State Neurosurgical Societies Resident Award: The utilization of
      carotid endarterectomy by neurosurgeons in the United States from 1990 to 2000.

PMID- 15571163
TI  - Section on tumors: Young Investigator Award: Local release of carboplatin via an
      Alzet mini-osmotic pump prolongs survival in a rat brainstem tumor model.

PMID- 15571164
TI  - Section on tumors: Mahaley Clinical Research Award: Primary sarcomas of the skull
      base: an analysis of 63 cases.

PMID- 15571165
TI  - Section on cerebrovascular surgery: Galbraith Award: Endothelial nitric oxide
      synthase (eNOS) and heme oxygenase-1 (HO-1) gene polymorphisms predict
      susceptibility to aneurysmal subarachnoid hemorrhage (SAH) and post-SAH cerebral
      vasospasm.

PMID- 15571166
TI  - Introduction of inactivated poliovirus vaccine into oral poliovirus vaccine-using
      countries.
AB  - Given the progress already made towards the goal of global eradication of
      poliomyelitis LE (polio), the risk of paralytic poliomyelitis is changing in many
      geographical areas. Vaccination against polio will need to continue because of
      the threat of wild poliovirus importation. However, an increasing number of polio
      free countries are determining that the risk of paralytic poliomyelitis
      associated with continued routine immunization using oral poliovirus vaccine
      (OPV) is greater than the risk of importation or laboratory handling of wild
      poliovirus. Some of these countries have introduced inactivated poliovirus
      vaccine (IPV)--a safe and effective alternative for routine immunization--using
      one of two approaches: replacement of OPV by IPV and introduction of a sequential
      IPV/OPV schedule. Countries considering such changes should conduct a thorough
      evaluation of the epidemiological, financial and operational implications before
      finalizing a change in policy. Tropical developing countries pose a special
      challenge for policy formulation on IPV. In these countries, given the unresolved
      issues related to the immunogenicity of IPV when administered in the WHO/Expanded
      Programme on Immunization (EPI) vaccination schedule, the continued focal
      circulation of wild poliovirus on two continents, the relatively high cost of IPV
      and the operational complexities of introducing this vaccine, WHO does not--as of
      July 2003--recommend the adoption of IPV alone or in a sequential schedule. It is
      expected that this position will be reviewed late 2004 and, if appropriate,
      revised according to the additional information that has become available on IPV
      effectiveness, logistic implications, and on further progress towards polio
      eradication. WHO is encouraging operational studies and introduction projects to
      evaluate these issues.

PMID- 15571168
TI  - Cholera epidemic in Basra, Iraq: capacity-building, preparedness and control.

PMID- 15571167
TI  - Progress towards poliomyelitis eradication in Afghanistan and Pakistan, January
      2002 to May 2003.

PMID- 15571169
TI  - Pertussis in Bulgaria, 1952-2001: 50 years of surveillance.

PMID- 15571170
TI  - Severe acute respiratory syndrome (SARS): over 100 days into the outbreak.

PMID- 15571171
TI  - Outbreak(s) of Ebola haemorrhagic fever, Congo and Gabon, October 2001-July 2002.

PMID- 15571172
TI  - Progress towards global poliomyelitis eradication: preparation for the oral
      poliovirus vaccine cessation era.

PMID- 15571173
TI  - Antibiotics in the management of shigellosis.

PMID- 15571174
TI  - Recommended composition of influenza virus vaccines for use in the 2005 influenza
      season.

PMID- 15571175
TI  - Human African trypanosomiasis: emergency action in southern Sudan.

PMID- 15571176
TI  - Chronic renal failure: oxidative stress, endothelial dysfunction and wine.
AB  - Atherosclerosis development is accelerated in chronic renal failure (CRF) and is
      the major cause of death in this clinical condition. An increased oxidative
      stress and an endothelial dysfunction, with their complex interrelationships, are
      relevant aspects of atherogenesis in CRF patients and might be targets for
      treatment. Many studies have underlined the cardiovascular protection provided by
      a moderate wine consumption. This beneficial effect is due to both alcohol and
      nonalcoholic components of wine including several phenolic molecules such as
      quercetin and resveratrol. Wine polyphenols have antioxidant properties and
      favorably influence endothelial function, in particular by stimulating nitric
      oxide-mediated vasodilation and inhibiting the endothelin-1 pathway. The possible
      advantage of a moderate wine consumption in CRF patients can be hypothesized and
      deserves clinical investigation.

PMID- 15571177
TI  - Analysis of macrophages in urine sediments in children with IgA nephropathy.
AB  - AIM: Although infiltrating macrophages found in renal biopsy specimens have been
      accepted as a useful marker for evaluating the activity of IgA nephropathy
      (IgAN), it is difficult to perform renal biopsies repeatedly, especially in
      children. To establish a more convenient and noninvasive method for estimating
      the degree of macrophage infiltration we examined the number of macrophages in
      urinary sediments. PATIENTS AND METHODS: Ten ml of morning urine were collected
      from 30 children with IgAN, 10 with thin basement membrane disease (TBMD), 8 with
      idiopathic renal hemorrhage (IRH) which was defined as nonglomerular hematuria
      due to nutcracker phenomenon revealed on ultrasonography, and 10 healthy children
      as controls. Ten of the 30 children with IgAN were treated with combination
      therapy comprising prednisolone, warfarin and dipyridamole and urine samples were
      collected weekly during the period of treatment. Two microl of the urine sediment
      were smeared on glass slides, dried and stained with a monoclonal antibody to
      human macrophages (anti-CD68, PG-M1) followed by a FITC-conjugated secondary
      antibody. After staining with propidium iodide (PI), the cells were examined by
      fluorescence microscopy with cells stained with both FITC and PI being counted as
      macrophages. In addition, anti-CD68 staining was used to quantify macrophage
      infiltration in renal biopsies from the same group of IgAN patients. RESULTS: The
      number of urine macrophages in children with IgAN was significantly higher than
      in children with TBMD and IRH as well as the control group (p < 0.01), whereas
      that was similar among TBMD, IRH and healthy children. In IgAN, there was a
      significant correlation between urine macrophage number and the activity index (p
      < 0.01), proteinuria (p < 0.01) and urine WBC count (p < 0.01). In addition,
      there was also a significant correlation between urine macrophage number and
      glomerular (p < 0.05) as well as interstitial macrophage infiltration (p < 0.01).
      In children with IgAN who received combination therapy, urine macrophage number
      decreased significantly (p < 0.01) in the 1st week of treatment whilst the degree
      of proteinuria decreased significantly (p < 0.01) in the 4th week. CONCLUSION:
      Urinary macrophage number may represent a noninvasive and straightforward
      estimate of the pathological activity evident in renal biopsy specimens, and may
      also be a more sensitive indicator than proteinuria of the therapeutic effect of
      interventional treatments in childhood IgAN.

PMID- 15571178
TI  - Evolution and predictive power of serum cystatin C in acute renal failure.
AB  - AIMS: The serum concentration of cystatin C has recently been proposed as a
      better indicator of glomerular filtration rate (GFR) than plasma creatinine.
      Little is known about cystatin C in critical illness. We assessed serum cystatin
      C as a marker of renal function in acute renal failure (ARF) and its power in
      predicting survival of ARF patients. MATERIAL: 202 consecutive adult patients
      admitted into the intensive care unit (ICU) during a period of 9 months. METHOD:
      Serum cystatin C, plasma creatinine and plasma urea were measured on admission,
      daily during the first 3 days, and 5-7 times a week during the rest of the ICU
      stay. The patients with and without ARF were compared by the Mann-Whitney U-test.
      The correlation between different variables was calculated by Spearman's
      correlation. Forward stepwise multiple regression analysis was performed to test
      independent predictors of mortality. The positive predictive value of serum
      cystatin C and plasma creatinine for ARF and mortality was calculated by ROC
      analysis. RESULTS: ARF occurred in 54 patients (27%). Serum cystatin C showed
      excellent positive predictive value for ARF in critical illness by ROC analysis.
      In acute renal dysfunction, abnormal values of serum cystatin C and plasma
      creatinine appeared equally quickly (median 3 days). The diagnosis of ARF, the
      day 1 Apache II score and admission plasma creatinine appeared as independent
      predictors of hospital mortality. ROC analysis showed only weak predictive power
      for serum cystatin C and plasma creatinine regarding hospital mortality.
      CONCLUSIONS: Serum cystatin C was as good as plasma creatinine in detecting ARF
      in intensive care patients. Neither marker was clinically useful in predicting
      mortality.

PMID- 15571179
TI  - Kidney biopsy and power Doppler imaging.
AB  - BACKGROUND: Practically, all complications of kidney biopsy are connected with
      hemorrhage. In the last years, the use of color Doppler sonography in monitoring
      kidney biopsies was being described, later the possibility of using power Doppler
      (PD) in performing kidney biopsies was presented. PD depicts the amplitude, or
      power, of Doppler signals rather than the frequency shift. This allows detection
      of a larger range of Doppler shifts and thus better visualization of small
      vessels, but at the expense of directional and velocity information. PATIENTS AND
      METHODS: Biopsy of native kidneys was performed in 144 patients. We performed
      real-time ultrasound-guided biopsy with an automatic biopsy device, 2-4 MHz
      convex probe and modified 18 G tru-cut needles were used. The vessels in the
      region of the biopsy were imaged with color Doppler sonography and with PD
      immediately before, after and the day following biopsy. RESULTS: Adequate tissue
      for histologic diagnosis was obtained in all patients with average 3.28 attempts
      at biopsy (range from 2-5). Average 24.15 (range from 7-58) glomeruli were
      obtained during each session. We observed complications in 6 (4.2%) patients,
      macrohematuria was presented in 4, and small hematoma with no need for
      intervention in 2 patients. In 138 (95.8%) patients, no complications were
      observed, microhematuria was present in 116 (80.6%) patients. CONCLUSIONS: In our
      study, complication rate of kidney biopsy was low and no complication requiring
      intervention was observed. Number of glomeruli obtained during each session was
      high. For better visualization of kidney vessels in biopsy path, PD was used.
      This additional kidney investigation itself does not essentially prolong the
      duration of the biopsy.

PMID- 15571180
TI  - Vitamin E-coated dialyzers reduce oxidative stress related proteins and markers
      in hemodialysis--a molecular biological approach.
AB  - BACKGROUND: Hemodialysis patients (HD) are exposed to oxidative stress which
      contributes to cardiovascular disease and accelerated atherosclerosis, major
      causes of mortality in these patients. A new dialysis membrane coated with
      vitamin E has been proposed against oxidative stress and atherosclerosis due to
      their ability to inhibit lipid peroxidation by interacting with scavengers. The
      mechanisms however are not completely clarified. This study evaluated, using a
      molecular biology approach, the effect of 6 months treatment with vitamin E
      modified dialyzers, CL-E, on the gene expression of oxidative stress related
      proteins and markers. PATIENTS AND METHODS: To this end, the gene expression of
      p22phox, a NAD(P)H oxidase subunit closely linked with the generation of
      superoxide anions and of Heme oxygenase-1 (HO-1), induced by and protective from
      oxidative stress, were evaluated by RT-PCR in mononuclear cells from 5 patients
      under 3 times a week chronic bicarbonate dialysis. Hydroperoxide (HPO) and total
      antioxidant power (AOP) plasma levels were evaluated at 3 and 6 months of
      treatment. HPO was also evaluated in 8 patients under CL-E treatment for 1 year
      and compared with 8 patients treated with cuprammonium-ryon filter (TAF).
      RESULTS: p22phox mRNA decreased from 0.61 +/- 0.05 d.u. to 0.48 +/- 0.03, p <
      0.01 while HO-1 increased from 0.55 +/- 0.04 d.u. to 0.62 +/- 0.03, p < 0.01. HPO
      decreased in CL-E treated patients: from 2.72 +/- 0.26 microM to 1.45 +/- 0.27 at
      3 months (p < 0.001) to 0.87 +/- 0.11, p < 0.001 at 6 months, while AOP
      increased: from 752 +/- 90 mmol/L to 1057 +/- 105, p < 0.001 at 6 months. HPO was
      also reduced in 1 year Excebrane CL-E treated patients compared with cuprammonium
      treated patients: 2.25 +/- 0.3 vs. 1.42 +/- 0.11 microM, p < 0.001. CONCLUSION:
      The reduced expression of oxidative stress related proteins and markers gives
      further support to the efficacy of the use of Vitamin E coated dialysers for the
      prevention or slowing progression of cardiovascular disease and atherosclerosis,
      major complications and causes of mortality in these patients in which oxidative
      stress plays a pivotal role.

PMID- 15571181
TI  - The mechanism of hypoglycemia caused by hemodialysis.
AB  - BACKGROUND: Although it is well-known that plasma glucose concentration ((G)p)
      decreases during hemodialysis, the precise mechanism underlying this decrease has
      not yet been fully elucidated. The aim of the present study was to investigate
      the mechanism underlying hemodialysis-induced decrease (HID) in (G)p during the
      dialysis in vivo or in vitro. METHODS: Using high CO2/ HCO3- dialysate, we
      measured (G)p by a hexose kinase method ((G)pHK) and concentrations of
      electrolytes, as well as pH, PCO2 and PO2 for both plasma and dialysate samples
      at pre- and postdialyzer sites obtained from hemodialysis patients with
      nondiabetic chronic renal failure (CRF). Furthermore, we studied the effect of
      PCO2 and acetazolamide (ACZ) on the changes in (G)pHK during the dialysis in
      vitro. RESULTS: After the first dialysis of CRF patients, the (G)pHK decreased
      from 118.3 +/- 18.0 to 98.6 +/- 5.7 mg/dl (p < 0.05), the latter value being
      significantly lower than glucose concentration in dialysate samples
      (approximately 105 mg/dl) at predialyzer sites. In the experiments of blood
      samples from healthy volunteers, (G)pHK decreased significantly after elevating
      or lowering CO2 level in the dialysates. In contrast, when the difference in PCO2
      between the blood and dialysate was reduced, the HID in (G)pHK was abolished
      during hemodialysis. The addition of 10(-4) M ACZ to the blood samples completely
      prevented the development of HID in (G)pHK caused by the perfusion of high or low
      CO2/HCO3- dialysates. CONCLUSIONS: During hemodialysis using high CO2/HCO3-
      dialysate, the HID in (G)p results from the diffusion of glucose from plasma into
      erythrocytes, probably due to the consumption of glucose resulting from the
      accelerated anaerobic metabolism induced by the changes in the cytoplasmic pH of
      erythrocytes.

PMID- 15571182
TI  - Ethanol/trisodium citrate for hemodialysis catheter lock.
AB  - AIMS: The objective of this study was to confirm the compatibility of ethanol and
      4% trisodium citrate (TSC) for potential use as a catheter locking solution.
      METHODS: Increasing concentrations of ethanol were combined with 4% TSC in glass
      test tubes and stored at 37 degrees C over 72 hours. Each tube was visually
      inspected to determine the highest compatible concentration. To confirm visual
      compatibility, HPLC analysis was used to compare the concentration of TSC in
      control solutions (n = 6) to solutions containing both TSC and the highest
      concentration of ethanol that was visually compatible (n = 6). Compatibility in
      carbothane hemodialysis catheters was then confirmed in vitro. RESULTS: Results
      of the compatibility tests indicated that 30% ethanol was the maximum
      concentration visually compatible with 4% TSC. Ethanol concentrations of 35% or
      above form a crystalline precipitate in the glass test tubes within 72 hours.
      HPLC analysis showed no difference in the concentration of TSC in the control
      solutions compared to the TSC/ethanol solutions when incubated in glass test
      tubes. A slight, but statistically significant increase in the TSC concentration
      (1.27%; p < 0.0001) was observed when the ethanol/TSC solution was incubated in
      carbothane hemodialysis catheters. This slight increase may be due to ethanol
      absorption into the catheter polymer. Further studies are underway to determine
      if an ethanol/TSC lock affects the mechanical properties of these carbothane
      hemodialysis catheters. CONCLUSIONS: We conclude that 30% ethanol is compatible
      with 4% trisodium citrate in carbothane hemodialysis catheters in vitro. Until
      the lock's affect on carbothane hemodialysis catheters is known, it cannot yet be
      recommended for clinical use.

PMID- 15571183
TI  - Ascites reinfusion dialysis (ARD) for renal failure with refractory ascites.
AB  - BACKGROUND: Dialysis is difficult for patients who have simultaneous liver and
      kidney failure. Effective mobilization of ascites is rare, and hypotension is
      common. Combining repeated paracentesis with continuous renal replacement therapy
      can achieve effective volume removal with hemodynamic stability, but requires
      intensive care unit resources. Large amounts of albumin are lost from the body in
      the drained ascites. Combining ascites reinfusion with hemodialysis is a
      potential alternative therapy. METHODS: Eight treatments were undertaken in 3
      patients with refractory ascites in the setting of acute onset renal failure.
      Hemodialysis was unsuccessful due to hypotension in each case. Two patients were
      treated twice, and 1 patient was treated 4 times. Each patient underwent
      hemodialysis with reinfusion of ascites directly into the blood inlet of the
      dialysis machine. Weight, blood urea nitrogen, albumin and platelet counts were
      measured before and after treatment. Hemodynamic tolerance was assessed, and
      patients were observed for the development ofencephalopathy, disseminated
      intravascular coagulation, infection and hemodynamic decompensation. RESULTS: All
      patients survived. There was 1 episode of transient hemoperitoneum, but no
      encephalopathy, GI bleeding or infection. One patient recovered renal function,
      and the other 2 were discharged ambulatory to chronic hemodialysis programs.
      Blood pressure was supported easily during therapy, despite removal of 3-8 kg of
      fluid. Platelet counts decreased by 27,000 +/- 13,000, and albumin increased by
      0.5 +/- 0.2 g/dl. All values returned to baseline over the next 1-4 days.
      CONCLUSIONS: Ascites recirculation with dialysis is a safe and effective therapy
      for patients with refractory ascites and severe renal failure, which can be
      carried out in routine inpatient and outpatient settings. Hemodynamic tolerance
      was good and thrombocytopenia was modest.

PMID- 15571184
TI  - Evaluation of salivary parameters and dental status in adult hemodialysis
      patients.
AB  - AIMS: Caries is a multifactor disease, and impaired stimulated salivary flow rate
      and buffering capacity are the best-known risk factors. The salivary flow rate,
      pH, buffering capacity and DMFT (decayed, missing and filled teeth) index of
      adult hemodialysis patients were compared with those of healthy controls.
      MATERIAL AND METHODS: Seventy-two (34 F, 38 M, mean age: 45.05 +/- 14.15 years)
      hemodialysis patients and 50 (26 F, 24 M, mean age: 43.92 +/- 18.80 years)
      control saliva were collected after prestimulation and expressed as ml/min.
      Salivary pH and buffering capacity were measured (Ericsson method). The dental
      examinations were performed according to WHO criteria and DMFT index was
      calculated. Statistical analysis was performed with Student t-test and Pearson
      correlation test. RESULTS: The patients' mean salivary flow rate was 0.69 +/-
      0.31 ml/min, pH, 8.15 +/- 0.72, buffering capacity, 6.83 +/- 0.71 and DMFT index
      was 11.91 +/- 8.73. The salivary flow rate was less than the controls (p <0.001),
      but salivary pH and buffering capacity were higher (both p < 0.001). There was no
      difference in DMFT index between groups (p > 0.05). There was no significantly
      negative correlation between DMFT index and stimulated salivary flow rate, pH but
      there was a positive correlation with buffering capacity (r = 0.286, p < 0.05) in
      the patients. Moreover, there was no significantly positive correlation between
      stimulated salivary flow rate and pH buffering capacity in these patients.
      CONCLUSIONS: Salivary flow rate of hemodialysis patients was less than the
      hyposalivary limit. Salivary pH and buffering capacity were both above the
      reference values, but DMFT index of hemodialysis patients did not differ from
      that of controls. However, caries and related dental infections may lead to
      serious problems in infection-prone hemodialysis patients, so these patients
      should have regular dental examinations and careful treatments.

PMID- 15571185
TI  - Temporal arteritis with pauci-immune glomerulonephritis: a systemic disease.
AB  - Temporal arteritis is easily diagnosed and responds gratifyingly to treatment.
      Renal complications are unusual, but nevertheless occur. Earlier, an association
      between pauci-immune glomerulonephritis and temporal arteritis was shown. We
      present a patient who clearly had temporal arteritis but also developed cerebral
      hemorrhage, pulmonary infiltrates related to granulomatous pulmonary vasculitis,
      and pauci-immune glomerulonephritis. We suggest that temporal arteritis is
      neither always localized nor temporal. Instead, the condition can be a lethal,
      systemic disease. Renal involvement in patients with temporal arteritis is not
      common and the presence of glomerulonephritis is rare [Jennette and Falk 1994].
      Lenz et al. [1998] described a patient who developed vision loss, optic nerve
      atrophy, elevated erythrocyte sedimentation rate, a positive rheumatoid factor
      and terminal glomerulonephritis. The renal biopsy showed focal and segmental
      necrotizing glomerulonephritis, despite negative antineutrophil cytoplasmatic
      antibodies (ANCA), antinuclear antibodies and antiglomerular basement membrane
      antibodies. Giant cells were identified in the necrotic vessel walls within the
      kidney. Immunofluorescence was negative and a diagnosis of ANCA-negative pauci
      immune glomerulonephritis was made. The patient did not respond to
      immunosuppression and developed end-stage renal disease. Although the clinical
      attributes were consistent with temporal arteritis, no temporal artery biopsy was
      done in that patient. We recently treated a patient with temporal arteritis and
      pauci-immune glomerulonephritis. Our patient's course was somewhat different in
      comparison to the patient described by Lenz et al. [1998].

PMID- 15571186
TI  - Dent's disease: identification of a novel mutation in the renal chloride channel
      CLCN5.
AB  - Dent's disease is an inherited tubulopathy caused by a mutation in the CLCN5
      chloride channel gene. It is characterized by low-molecular weight proteinuria,
      hypercalciuria, nephrolithiasis or nephrocalcinosis, rickets and eventual
      progressive renal failure. Onset of clinical symptoms show a great variability,
      making a diagnosis at an early stage of the disease often difficult. Given the
      variably clinical picture, genetic analysis can provide a reliable method to
      confirm the diagnosis. Here, we report on the case of a patient with progressive
      renal failure showing signs of a tubular lesion and symptoms of Dent's disease.
      Although this rare disease was suspected by means of the clinical features, it
      was genetic analysis that confirmed the diagnosis and revealed a novel mutation
      in the CLCN5 gene.

PMID- 15571187
TI  - Group B Streptococcus (Streptococcus agalactiae) peritonitis associated with
      continuous ambulatory peritoneal dialysis (CAPD).
AB  - Streptococcus agalactiae typically induces serious infections in pregnant women
      and newborns. Nonpregnant adult patients can also be infected and mortality rate
      exceeds 40%. CAPD peritonitis is very rarely induced by S. agalactiae. Seven
      cases have been described previously and all had a very severe course, which
      included bacteremia, septic shock and death. A 27-year-old male with end-stage
      renal disease due to membranoprolipherative glomerulonephritis type I, who was on
      CAPD for 17 months, was admitted with the clinical and laboratory picture of CAPD
      peritonitis. Severe abdominal pain, shaking chills and fever 38.5 microC were
      also observed at presentation. Streptococcus agalactiae was isolated from the
      peritoneal fluid and blood culture was sterile. Under treatment with ceftazidime
      and tobramycin (i.p.) and vancomycin (i.v.) cultures became negative after 48
      hours, abdominal symptoms resolved after 12 days and WBC count in the dialysate
      normalized after 14 days. As a possible source of infection the patient's partner
      was shown to be a vaginal carrier of a clone of S. agalactiae identical to that
      isolated in the peritoneal fluid. S. agalactiae is a rare cause of CAPD
      peritonitis with potentially very serious consequences. Anal or genital tract
      colonization is, in general, the source of contamination with S. agalactiae. The
      microbiological findings in the case presented here suggest that colonization of
      the patient or of his close environment may be important in the pathogenesis of
      S. agalactiae-induced CAPD peritonitis.

PMID- 15571188
TI  - Secondary erythrocytosis associated with distal renal tubular acidosis.
AB  - AIMS: Diagnosis and classification of renal tubular acidosis (RTA) have
      traditionally been made on the basis of functional studies. Despite recent
      expanding knowledge about the molecular abnormalities involved in renal
      bicarbonate (HCO3-) and H+ transport, the pathophysiology of secondary
      erythrocytosis in association with distal RTA remains obscure. CASE HISTORY: A 2
      month-old boy with severe hyperchloremic metabolic acidosis with positive urine
      anion gap was diagnosed with distal RTA. Replacement therapy with sodium
      bicarbonate and potassium citrate succeeded in improving his metabolic acidosis
      and growth. His renal function remained normal. He had persistent erythrocytosis.
      CONCLUSION: Secondary erythrocytosis is a rarely reported association of distal
      RTA. It may increase the risk of thromboembolism.

PMID- 15571189
TI  - Different glomerular pathologies in sickle cell anemia.

PMID- 15571190
TI  - A case of acute renal failure, rhabdomyolysis and disseminated intravascular
      coagulation associated with severe exercise-induced hypernatremic dehydration.

PMID- 15571191
TI  - ACTH therapy in nephrotic syndrome induced by idiopathic membranous nephropathy.

PMID- 15571192
TI  - A model for all.

PMID- 15571193
TI  - The word "accident": no chance, no error, no destiny.

PMID- 15571194
TI  - Effectiveness of hospital staff mass-casualty incident training methods: a
      systematic literature review.
AB  - INTRODUCTION: Recently, mass-casualty incident (MCI) preparedness and training
      has received increasing attention at the hospital level. OBJECTIVES: To review
      the existing evidence on the effectiveness of disaster drills, technology-based
      interventions and tabletop exercises in training hospital staff to respond to an
      MCI. METHODS: A systematic, evidence-based process was conducted incorporating
      expert panel input and a literature review with the key terms: "mass casualty",
      "disaster", "disaster planning", and "drill". Paired investigators reviewed
      citation abstracts to identify articles that included evaluation of disaster
      training for hospital staff. Data were abstracted from the studies (e.g., MCI
      type, training intervention, staff targeted, objectives, evaluation methods, and
      results). Study quality was reviewed using standardized criteria. RESULTS: Of 243
      potentially relevant citations, 21 met the defined criteria. Studies varied in
      terms of targeted staff, learning objectives, outcomes, and evaluation methods.
      Most were characterized by significant limitations in design and evaluation
      methods. Seventeen addressed the effectiveness of disaster drills in training
      hospital staff in responding to an MCI, four addressed technology-based
      interventions, and none addressed tabletop exercises. The existing evidence
      suggests that hospital disaster drills are effective in allowing hospital
      employees to become familiar with disaster procedures, identify problems in
      different components of response (e.g., incident command, communications, triage,
      patient flow, materials and resources, and security) and provide the opportunity
      to apply lessons learned to disaster response. The strength of evidence on other
      training methods is insufficient to draw valid recommendations. CONCLUSIONS:
      Current evidence on the effectiveness of MCI training for hospital staff is
      limited. A number of studies suggest that disaster drills can be effective in
      training hospital staff. However, more attention should be directed to evaluating
      the effectiveness of disaster training activities in a scientifically rigorous
      manner.

PMID- 15571195
TI  - Information-sharing in out-of-hospital disaster response: the future role of
      information technology.
AB  - Numerous examples exist of the benefits of the timely access to information in
      emergencies and disasters. Information technology (IT) is playing an increasingly
      important role in information-sharing during emergencies and disasters. The
      effective use of IT in out-of-hospital (OOH) disaster response is accompanied by
      numerous challenges at the human, applications, communication, and security
      levels. Most reports of IT applications to emergencies or disasters to date,
      concern applications that are hospital-based or occur during non-response phases
      of events (i.e., mitigation, planning and preparedness, or recovery phases). Few
      reports address the application of IT to OOH disaster response. Wireless peer
      networks that involve ad hoc wireless routing networks and peer-to-peer
      application architectures offer a promising solution to the many challenges of
      information-sharing in OOH disaster response. These networks offer several
      services that are likely to improve information-sharing in OOH emergency
      response, including needs and capacity assessment databases, victim tracking,
      event logging, information retrieval, and overall incident management system
      support.

PMID- 15571196
TI  - The development of conceptual models for mass-gathering health.
AB  - Mass gatherings are an increasingly common feature of modern society. However,
      descriptive papers that focus on a single event or event type, dominate the
      literature, and, while these contribute to our understanding of the patient care
      required at such events, they do not provide an adequate analysis of the health
      effects of the mass-gathering phenomenon itself. This paper argues for the
      development of conceptual models and a research template for mass-gathering
      research. The development of theory and conceptual models would promote a better
      understanding of the health effects of mass gatherings. Two preliminary
      conceptual models are presented as a means to encourage further debate about the
      dominant influences on the health of people where crowds gather and to promote
      less superficial forms of analysis of the research data. These conceptual models
      are based on the idea that mass-gathering health can be understood as an inter
      relationship between three domains: (1) the biomedical; (2) the environmental;
      and (3) the psychosocial. Key features influence the rate of injury and illness
      and characterize each domain. These key features are more or less well-understood
      and combine to produce an effect--the patient presentation rate, and a response-
      the health plan. A new element, the latent potential for injury and illness, is
      introduced as a mechanism for describing a biomedical precursor state important
      in assessing health risk during mass gatherings.

PMID- 15571197
TI  - Hazardous substances releases causing fatalities and/or people transported to
      hospitals: rural/agricultural vs. other areas.
AB  - INTRODUCTION: Mass-casualty and hospital preparedness has been analyzed widely.
      However, information regarding the types of areas where these events occur is
      limited. Therefore, the characteristics of acute hazardous substances releases
      resulting in death/multiple-victim events occuring in rural/agricultural areas
      and in all other areas were studied and compared. METHODS: Data reported to the
      Hazardous Substances Emergency Events Surveillance (HSEES) system from 16 state
      health departments during 1993-2000 were used to examine factors associated with
      events with death/multiple victims involving acute release of hazardous
      substances. A death/multiple-victim event is defined as any event resulting in a
      death and/or at least five people being transported to a hospital. RESULTS: Of a
      total of 43,133 events, 6661 occurred in rural/agricultural areas. Of these, 107
      were death/multiple-victim events with 632 victims, of whom 91 died and 77 were
      hospitalized. All other areas had 472 death/multiple-victim events with 7981
      victims, of whom 116 died and 413 were hospitalized. Death/multiple-victim events
      in rural/agricultural areas were more likely to be associated with transportation
      (Proportional Ratio (PR) = 4.1, 95% CI = 3.1-5.4) and fires and/or explosions (PR
      = 1.4, 95% CI = 0.95-2.0) than were death/multiple-victim events in all other
      areas. Among transportation-related events in rural/agricultural areas, 19 were
      associated with air transport--mainly crop dusters--and resulted in 18 deaths.
      Responders were three times more likely to be injured in rural/agricultural
      areas. Of responders, volunteer firefighters constituted 52% compared with 6.7%
      in all other areas. The most frequently released chemicals in rural/agricultural
      areas were ammonia, chlorine, and pesticides. In all other areas, ammonia,
      chlorine, hydrochloric acid, carbon monoxide, and 0-chlorobenzylidene
      malononitrile, a tearing agent often associated with an illegal or unauthorized
      act, were released most frequently. CONCLUSIONS: Findings from this analysis
      suggest that remedial actions should address safety measures in both
      transportation and fixed facilities containing acute hazardous substances. These
      include regular maintenance of equipment, education of workers about the
      substances used in their facility, rigorous training and licensing of drivers and
      crop duster operators, and education and training of employees and first
      responders in the use of protective equipment. These activities may reduce the
      number of events, casualties, and costs associated with hazardous substance
      events.

PMID- 15571198
TI  - Health indicators for mothers and children in rural Herat Province, Afghanistan.
AB  - INTRODUCTION: Following years of conflict and neglect, major efforts now are
      underway to develop health policy and rehabilitate the health facilities in
      Afghanistan. As part of these efforts, there is a need to better understand the
      health status and health-seeking behaviors. As part of an effort to assist local
      non-governmental organizations (NGOs), a household survey of mothers with
      children under the age of five years was conducted in two rural districts of
      Herat Province, Karokh and Chesht-e-Sharif. METHODS: A two-stage, 30-cluster
      approach was used for each district. This included 622 mothers of 926 children
      under the age of five years living in the two districts. Outcome measures
      included demographic characteristics, antenatal services, immunization coverage,
      hemoglobin levels of the mothers, nutritional status and practices, environmental
      health indicators, recent illness, and health seeking behaviors. RESULTS: The
      mean value of ages of the mothers was 27 years with an average parity of 6.1.
      Less than 5% of mothers ever had attended school. Half of women had lost at least
      one child before the child reached the age of five years. Under-five-year
      mortality was estimated at 325. Only 29% of the women had attended an antenatal
      clinic during their last pregnancy. Virtually all deliveries occurred at home.
      Only 7.6% of women had received three doses of tetanus toxoid. Less than 9% of
      the children 12-59 months of age were fully immunized. According to the
      measurements of mid-upper-arm circumference (MUAC), 11% of children were
      malnourished. Although breastfeeding almost was universal, greater than one-third
      of the women did not start breastfeeding until the second day after delivery.
      Protected water sources and appropriate control of feces were lacking in both
      districts. In the previous two weeks, 45.7% of children had experienced diarrhea,
      and dysentery had occurred in 10%. Fever had been present in one-quarter of the
      children. CONCLUSIONS: Household health indicators indicate serious maternal and
      child health concerns in these two districts. Of particular concern is the poor
      immunization coverage, lack of reproductive health service, and the prevalence of
      common childhood illness in these populations. The feeding practices for children
      and the anemia among mothers also raised concerns. Poor environmental health
      contributes substantially to childhood illness. Without special emphasis, efforts
      to rebuild the health sector are likely to reach the household level only late in
      the process. An aggressive program to integrate community development and
      promotion of sound health practices is needed to improve the health of the
      Afghanistan people.

PMID- 15571199
TI  - Daily stress and concept of self in Swedish ambulance personnel.
AB  - INTRODUCTION: This study investigated the prevalence of post-traumatic stress
      symptoms among professional ambulance personnel in Sweden and investigated the
      question: "Does self-knowledge have influence on how well one copes with the
      effects of daily work exposure from such events?" Little is known about the
      variables that might be associated with post-traumatic stress symptoms in high
      risk occupational groups such as ambulance service groups. METHODS: Data were
      gathered from ambulance personnel by means of an anonymous questionnaire. Survey
      responses of 362 ambulance personnel from the county of Vastra Gotaland were
      analyzed. A correlation was established between post-traumatic symptoms using the
      impact of event scale (IES-15) and the Professional Self-Description Form (PSDF).
      RESULTS: Of those who reported a traumatic situation, 21.5% scored > or =26 on
      the IES-15 subscale. Scores >26 indicate "PTSD caseness". There were significant
      differences on PSDF subscales between those presenting with or without post
      traumatic symptoms. CONCLUSIONS: The mental health and emotional well-being of
      ambulance personnel appear to be compromised by accident and emergency work. The
      high prevalence of PTSD symptoms in ambulance personnel indicates an inability to
      cope with post-traumatic stress caused by daily work experiences.

PMID- 15571200
TI  - Building the Tower of Babel: cross-border urgent medical assistance in Belgium,
      Germany and The Netherlands.
AB  - The border area between Germany, Belgium, and The Netherlands includes a
      substantial number of cooperative forms in the urgent medical assistance sector.
      Collaboration usually takes place in densely populated areas with cities or
      villages situated on or in proximity to the border. In some regions, definitive
      borders are not apparent to the extent that inhabitants often times are unaware
      of their existence. The border may pass directly through a built-up area with
      intense cross-border activity due to population residency, place of work,
      shopping, and recreational pursuits. To obtain a deeper insight into cross-border
      Urgent Medical Assistance (UMA), the Ministry of the Interior and Kingdom
      Relations (IKR) and the Ministry for Health, Welfare, and Sports (HWS) in The
      Netherlands commissioned research into cross-border UMA impediments and solutions
      at administrative, judicial, and operational level. The following central
      questions were presented for research: (1) What opportunities and impediments are
      presented in the area of cross-border, urgent medical assistance at
      administrative, legal, operational, and equipment employable level?; and (2)
      Which solutions may be submitted to tackle existing impediments? Two techniques
      were employed to answer the research questions. First, relevant documents were
      studied from extensive file and literature searches. File and literature search
      findings subsequently were tested in practice through interviews with relevant
      experts. Dutch ambulance services provide support to both their Belgian and
      German counterparts and vice versa. In the instance of cross-border ambulance
      deployment, relevant assistance services are subject to due observance of various
      legislations and regulations. Such regulations may restrict effective and
      efficient deployment of personnel and equipment at critical moments, because
      regulation discrepancies may arise over ambulance personnel's authorities,
      ambulance content, and deployment sequence. Discrepencies also may exist in the
      area of financial compensation concerning ambulance deployment and hospital
      admission. Gaining knowledge on their disparate systems and the opportunity to
      utilize the medical provisions of a neighboring country potentially in closer
      proximity to those in the victim's own country serves the best interests of the
      patient. Survival chances of a traumatized patient increase with the expedited
      arrival of medical assistance and increased speed of transportation to an
      appropriate hospital.

PMID- 15571201
TI  - Public health preparedness for mass-casualty events: a 2002 state-by-state
      assessment.
AB  - INTRODUCTION: The ongoing threat of a terrorist attack places public agencies
      under increasing pressure to ensure readiness in the event of a disaster. Yet,
      little published information exists regarding the current state of readiness,
      which would allow local and regional organizations to develop disaster
      preparedness plans that would function seamlessly across service areas. The
      objective of this study is to characterize state-level disaster readiness soon
      after September 2001 and correlate readiness with existing programs providing an
      organized response to medical emergencies. METHODS: During the first quarter of
      2002, a cross-sectional survey assessing five components of disaster readiness
      was administered in all 50 states. The five components of disaster readiness
      included: (1) statewide disaster planning; (2) coordination; (3) training; (4)
      resource capacity; and (5) preparedness for biological/chemical terrorism.
      RESULTS: Most states reported the presence of a statewide disaster plan (94%),
      but few are tested by activation (48%), and still fewer contain a bioterrorism
      component (38%). All states have designated disaster operations centers (100%),
      but few states have an operating communications system linking health and medical
      resources (36%). Approximately half of states offer disaster training to medical
      professionals; about 10% of states require the training. Between 22-48% of states
      have various contingency plans to treat victims when service capacity is
      exceeded. Biochemical protective equipment for health professionals is lacking in
      all but one state, and only 10% of states indicate that all hospitals have
      decontamination capabilities. States with a functioning statewide trauma system
      were significantly more likely to possess key attributes of a functioning
      disaster readiness plan. CONCLUSION: These findings suggest that disaster plans
      are prevalent among states. However, key programs and policies were noticeably
      absent. Communication systems remain fragmented and adequate training programs
      and protective equipment for health personnel are markedly lacking. Statewide
      trauma systems may provide a framework upon which to build future medical
      disaster readiness capacity.

PMID- 15571202
TI  - Testing emergency medical personnel response to patients with suspected
      infectious disease.
AB  - OBJECTIVES: In the United States (US), hospitals are required to have disaster
      plans and stage drills to test these plans in order to satisfy the Joint
      Accreditation Commission of Healthcare Organizations. The focus of this drill was
      to test if emergency response personnel, both prehospital and hospital, would
      identify a patient with a potentially communicable infectious disease, and
      activate their respective disaster plan. METHODS: Twelve urban/suburban emergency
      departments (ED) received patients via car and ambulance. Patients were moulaged
      to imitate a smallpox infection. Observers with checklists recorded what
      happened. The drill's endpoints were: (1) predetermined end time; (2)
      identification of the patient and hospital "lock-down"; and (3) breach of drill
      protocol. RESULTS: None of the ambulance personnel correctly identified their
      patients. Of the total 13 mock patients assessed in the ED, seven (54%) were
      identified by the ED staff as possibly being infected with a highly contagious
      agent and, in turn, the hospital's biological agent protocol was initiated. Of
      the correctly identified patients, five (71%) were placed in isolation, and the
      remaining two (29%), although not isolated, were identified prior to their ED
      discharge and the appropriate protocol was activated. The six remaining mock
      patients (46%) were incorrectly diagnosed and discharged. Of the hospitals that
      had correctly identified their "infected" patients, only two (29%) followed their
      notification protocol and contacted the local health department. CONCLUSION: This
      drill was successful in identifying this area's shortcomings, highlighted
      positive reactions, and raised some interesting questions about the ability to
      detect a patient with a possibly highly contagious disease.

PMID- 15571203
TI  - Remote site production of sterile purified water from available surface water.
AB  - A water purification and sterilization device was tested for its functional
      capabilities. Challenge water consisting of potable water augmented with
      bacteria, endotoxin, virus, suspended solids, and dissociable ions (sodium
      chloride, lead or arsenic salts) was passed through the device. The product water
      quality attributes were analyzed. The device demonstrated reduction in bacteria
      of >7 logs, endotoxin was reduced by >4 logs, virus was reduced by >4 logs, and
      dissociable ions were reduced by >3 logs. The product water of the device met the
      limits for a range of chemical entities specified by the United States
      Pharmacopeia and Association for the Advancement of Medical Instrumentation. The
      product water met the quality attributes of Sterile Water for Injection, USP,
      Sterile Purified Water, USP, and the Water for Dialysis. The device provides a
      logistical advantage in reducing the weight of transport of packaged water by 83%
      and the cube by 67%. It operates manually by gravity and is disposable after a
      single use. The device provides an effective alternative to the transport and use
      of packaged sterile water in remote locations by production of sterile water at
      the point-of-need using available water. It also is capable of producing safe
      drinking water following the production of clinical waters. This device has been
      cleared by the US Food and Drug Administration for production of three liters
      Sterile Purified Water, USP from Environmental Protection Agency (EPA) grade
      drinking water.

PMID- 15571204
TI  - Analysis of patient load data from the 2002 FIFA World Cup Korea/Japan.
AB  - INTRODUCTION: Past history of mass casualties related to international football
      games brought the importance of practical planning, preparedness, simulation
      training, and analysis of potential patient presentations to the forefront of
      emergency research. METHODS: The Japanese Ministry of Health, Labor, and Welfare
      established the Health Research Team (HRT-MHLW) for the 2002 FIFA World Cup game
      (FIFAWC). The HRT-MHLW collected patient data related to the games and analyzed
      the related factors regarding patient presentations. RESULTS: A total of 1661
      patients presented for evaluation and care from all 32 games in Japan. The
      patient presentation rate per 1000 spectators per game was 1.21 and the transport
      to-hospital rate was 0.05. The step-wise regression analysis identified that the
      patient presentations rate increased where access was difficult. As the number of
      total spectators increased, the patient presentation rate decreased. (p < 0.0001,
      r = 0.823, r2 = 0.677). CONCLUSION: In order to develop mass-gathering medical
      care plans in accordance with the types and sizes of mass gatherings, it is
      necessary to collect data and examine risk factors for patient presentations for
      a variety of events.

PMID- 15571205
TI  - Purine and pyrimidine metabolism: new challenges.

PMID- 15571206
TI  - Dedication to Francoise Roch-Ramel.

PMID- 15571207
TI  - Antimetabolites in the treatment of arthritis: current status of the use of
      antimetabolites.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by a chronic
      inflammation of the synovial joints and infiltration of blood-derived cells. In
      daily practice rheumatologists use the antimetabolites methotrexate (MTX) and
      leflunomide for the treatment of patients with rheumatoid arthritis. The current
      clinical status (efficacy/toxicity) of these 2 antimetabolites in the treatment
      of RA will be discussed.

PMID- 15571208
TI  - Two inhibitors of DNA-synthesis lead to inhibition of cytokine production via a
      different mechanism.
AB  - Methotrexate (MTX) and mycophenolic acid (MPA) are used in the clinic for their
      immunosuppressive properties. MTX is widely used for the treatment of rheumatoid
      arthritis (RA). MPA is used to prevent graft rejection and is now experimentally
      used in systemic lupus erythematosis and RA. It is known that both drugs
      interfere with DNA synthesis. However, the precise mechanism of action is still
      debated. We have analysed the effect of the drugs on cytokine production in whole
      blood during short cultures. The production of T-cell cytokines was inhibited by
      both drugs. MTX inhibits cytokine production because MTX induces apoptosis in
      activated T-cells. MPA inhibits cytokine production by preventing T-cells to
      progress to the S-phase of the cell cycle. Cytokine production by monocytes was
      slightly decreased by the drugs. The reason for this inhibition is not clear.
      These results indicate that T-cells are the main target cells of the
      immunosuppressive drugs MPA and MTX.

PMID- 15571209
TI  - Modification of cytokine milieu by A2A adenosine receptor signaling--possible
      application for inflammatory diseases.
AB  - Pro-inflammatory cytokine TNF-alpha (TNF) production from in vitro
      lipopolysaccharide (LPS)-stimulated human peripheral blood CD14+ cells (PB-CD14)
      was inhibited by A2A adenosine receptor (AdoR) (A2AR) or beta2 adrenergic
      receptor (ADR) (beta2R) signaling in a concentration-dependent manner. These
      inhibitory effects were presumably mediated by the increase in intracellular
      cAMP. Furthermore A2AR agonist and beta2R agonist synergistically inhibited the
      TNF production of LPS-stimulated PB-CD14 cells. These results suggest that the
      anti-inflammatory effect of extracellular adenosine is, at least in part, due to
      the modification of the cytokine milieu via A2A signaling, and that the targeting
      of both A2AR and beta2R may have strong therapeutic potential for the
      inflammatory diseases.

PMID- 15571210
TI  - Purine modulation of cytokine release during diuretic therapy of rheumatoid
      arthritis.
AB  - Since free radicals are implicated in rheumatoid arthritis (RA) and since uric
      acid is a free radical scavenger, we examined the effects of treating RA patients
      with with the diuretic bumetanide to try to improve their arthritic control.
      Seventy patients, aged 18-75 years, were randomised to receive bumetanide 4
      mg/day or placebo. Uric acid levels increased, but not that of other purines, in
      the blood of drug-treated patients compared with placebo-treated controls. There
      were no significant changes in clinical measurements of disease activity or in
      ESR or CRP levels. There were no over all differences in the blood levels of the
      cytokines, nor in the basal or stimulated production of cytokines from the blood
      cultures. The adenosine receptor agonist 5'N-ethylcarboxamido-adenosine (NECA)
      used to modify cytokine release in cultures of whole blood taken from the
      patients, depressed the release of tumour necrosis factor-alpha (TNFalpha), but
      failed to depress the release of interleukin-1b (IL-1b) or interleukin-6 (IL-6),
      a difference from earlier studies of healthy control subjects and, thus, a
      difference which may contribute to the disease activity.

PMID- 15571211
TI  - Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine
      oxidase, is safe and decreases serum urate in healthy volunteers.
AB  - In order to evaluate the safety, pharmacological properties, and urate-lowering
      efficacy of febuxostat, a non-purine, selective inhibitor of xanthine oxidase, a
      Phase 1, 2-week, multiple-dose, placebo-controlled, dose-escalation study was
      conducted in 154 healthy adults of both sexes. Daily febuxostat doses in the
      range 10 mg to 120 mg resulted in proportional mean serum urate reductions
      ranging from 25% to 70% and in proportional increases in maximum febuxostat
      plasma concentrations and area under plasma concentration versus time curves.
      Accompanying the hypouricemic effect were increases in serum xanthine
      concentrations, decreases in urinary uric acid excretion, and increases in
      urinary xanthine and hypoxanthine excretion, confirming inhibition of xanthine
      oxidase activity by febuxostat. Hepatic conjugation and oxidative metabolism were
      the major pathways of elimination of febuxostat from the body, and renal
      elimination did not appear to play a significant role. Although not uncommon,
      adverse events were mild and self-limited, and no deaths or serious adverse
      events were observed. Febuxostat is a safe and potent hypouricemic agent in
      healthy humans.

PMID- 15571212
TI  - PK/PD and safety of a single dose of TMX-67 (febuxostat) in subjects with mild
      and moderate renal impairment.
AB  - A single oral dose of 20 mg febuxostat was administered to subjects with normal,
      mild or moderate impairment in renal function. There was less than a 2-fold
      difference in AUC of plasma unchanged febuxostat among the renal function groups,
      and changes in plasma urate levels from pre-dose levels were not significant. A
      total of five adverse events were reported with all mild in severity. The results
      indicate that renal impairment will have little clinical impact on the
      pharmacokinetics (PK), pharmacodynamics (PD) and safety of the study drug.

PMID- 15571213
TI  - Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine
      selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in
      patients with gout and/or hyperuricemia.
AB  - The diurnal change of sUA and the effect of febuxostat on this change were
      investigated in 10 patients with gout and/or hyperuricemia. The diurnal sUA
      change after the last dose during the 4-week treatment phase (20 mg, QD) was
      almost the same as the pre-treatment value. Considering the dose, the AUC(obs)
      and Cmax of unchanged drug in patients with gout and/or hyperuricemia were
      estimated to be similar to those of healthy male adults. The results show that a
      6-week treatment with febuxostat is safe and well-tolerated in the target patient
      population for this drug.

PMID- 15571214
TI  - Pharmacokinetics/pharmacodynamics of Y-700, a novel xanthine oxidase inhibitor,
      in rats and man.
AB  - The pharmacokinetics and pharmacodynamics of a novel xanthine oxidase (XO)
      inhibitor, Y-700, were evaluated in rats and healthy male volunteers. In a rat
      model of hyperuricemia, oral Y-700 (0.3-10 mg/kg) showed a more potent and a
      longer-lasting hypouricemic action than allopurinol. A single oral dosing of Y
      700 (5, 20 or 80 mg) to volunteers caused a dose-dependent reduction of serum
      uric acid levels indicating close relationship to plasma concentrations of the
      compound. In addition, Y-700 was hardly excreted in urine but mainly excreted in
      feces in rats and volunteers. These results suggested that Y-700 is a new
      effective inhibitor of XO in rats and humans with high oral bioavailability being
      predominantly eliminated via the liver unlikely to allopurinol.

PMID- 15571215
TI  - Detection of prothrombin and osteopontin in a renal stone found in a
      hyperuricemic patient using 2D-PAGE and LC-MS analysis.
AB  - The liquid chromatography-mass spectrometry (LC-MS) following on from the two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) technique was applied
      for the analysis of proteins in a renal stone found in a hyperuricemic patient.
      This technique was sensitive enough to detect small quantities of proteins even
      in a renal stone.

PMID- 15571216
TI  - EPR spin trapping of a radical intermediate in the urate oxidase reaction.
AB  - Urate oxidase, or uricase (EC 1.7.3.3), is a peroxisomal enzyme that catalyses
      the oxidation of uric acid to allantoin. The chemical mechanism of the urate
      oxidase reaction has not been clearly established, but the involvement of radical
      intermediates was hypothesised. In this study EPR spectroscopy by spin trapping
      of radical intermediates has been used in order to demonstrate the eventual
      presence of radical transient urate species. The oxidation reaction of uric acid
      by several uricases (Porcine Liver, Bacillus Fastidiosus, Candida Utilitis) was
      performed in the presence of 5-diethoxyphosphoryl-5-methyl-pyrroline-N-oxide
      (DEPMPO) as spin trap. DEPMPO was added to reaction mixture and a radical adduct
      was observed in all cases. Therefore, for the first time, the presence of a
      radical intermediate in the uricase reaction was experimentally proved.

PMID- 15571217
TI  - An unusual pyridine nucleotide accumulating in erythrocytes: its identity and
      positive correlation with degree of renal failure.
AB  - We have investigated an unusual nucleotide that accumulates, with precursors, in
      the erythrocytes of patients in uraemia. This nucleotide is related chemically to
      the NAD breakdown product, N1-methyl-2-pyridone-5-carboxamide (Me2Py), found in
      high concentrations in the plasma of uraemic patients. Both Me2Py and the
      nucleotide accumulate to high concentrations in the blood during uraemia: our
      investigations of samples from renal out-patients have provided information on a
      plausible link between the two compounds.

PMID- 15571218
TI  - Identification of two novel mutations in adenine phosphoribosyltransferase gene
      in patients with 2,8-dihydroxyadenine urolithiasis.
AB  - Five mutations in the adenine phosphoribosyltransferase (APRT) gene have been
      described in Japanese patients with APRT deficiency. We investigated the APRT
      gene from three patients with APRT deficiency and two novel mutations, G133D and
      V84M, were determined.

PMID- 15571219
TI  - Medical diagnosis, management and treatment of Lesch Nyhan disease.
AB  - The aim of this presentation is to inform about Lesch Nyhan Disease from the
      point of view of the affected boys and their families living with the condition
      from day to day and also to show the importance of research in treating and
      managing the disease (In Caring for Children with Lesch Nyhan Disease--A Guide
      for Parents and Professionals; McCarthy, G.T., Ed.; PUMPA and Chailey Heritage
      Clinical Services: East Sussex, UK, 2002).

PMID- 15571220
TI  - The spectrum of mutations causing HPRT deficiency: an update.
AB  - Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase
      (HPRT) cause Lesch-Nyhan disease, which is characterized by hyperuricemia, severe
      motor disability, and self-injurious behavior. Mutations in the same gene also
      cause less severe clinical phenotypes with only some portions of the full
      syndrome. A large database of 271 mutations associated with both full and partial
      clinical phenotypes was recently compiled. Since the original database was
      assembled, 31 additional mutations have been identified, bringing the new total
      to 302. The results demonstrate a very heterogeneous collection of mutations for
      both LND and its partial syndromes. The differences between LND and the partial
      phenotypes cannot be explained by differences in the locations of mutations, but
      the partial phenotypes are more likely to have mutations predicted to allow some
      residual enzyme function. The reasons for some apparent exceptions to this
      proposal are addressed.

PMID- 15571221
TI  - The motor disorder of classic Lesch-Nyhan disease.
AB  - Reports describing the neurological features of Lesch-Nyhan disease (LND) vary
      widely, thereby implying the involvement of different neurological substrates.
      The movement abnormalities in 20 patients with LND were investigated. Dystonia
      was the most frequent and severe movement disorder. At rest, hypotonia was more
      frequent than hypertonia. These findings are compatible with basal ganglia
      dysfunction in LND.

PMID- 15571222
TI  - Clinical and biochemical manifestations and molecular characterization of the
      mutation HPRT Jerusalem.
AB  - A novel point mutation (I137T) was identified in the hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) encoding gene, in a patient with partial
      deficiency of the enzyme. The mutation, ATT to ACT (substitution of isoleucine to
      threonine), occurred at codon 137, which is within the region encoding the
      binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). The mutation caused
      decreased affinity for PRPP, manifested clinically as a Lesch-Nyhan variant
      (excessive purine production and delayed acquisition of language skills). The
      partial HPRT deficiency could be detected only by measuring HPRT activity in
      intact fibroblasts (uptake of hypoxanthine into nucleotides).

PMID- 15571223
TI  - Mutations in the hypoxanthine guanine phosphoribosyltransferase gene (HPRT1) in
      Asian HPRT deficient families.
AB  - Inherited mutation of hypoxanthine guanine phosphoribosyltransferase, (HPRT)
      gives rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified 34
      mutations in 28 Japanese, 7 Korean, and 1 Indian families with the patients
      manifesting different clinical phenotypes, including two rare cases in female
      subjects, by the analysis of all nine exons of HPRT from the genomic DNA and
      reverse transcribed mRNA using PCR technique coupled with direct sequencing.

PMID- 15571224
TI  - Disruption of the hypoxanthine-guanine phosphoribosyl-transferase gene caused by
      a translocation in a patient with Lesch-Nyhan syndrome.
AB  - In this study, we have identified a novel mechanism of mutation involving
      translocation between the HPRT1 loci and other loci on the X chromosome. In HRT
      25's cDNA obtained from a patient with Lesch-Nyhan syndrome, the upstream region
      of exon 3 was amplified, but the full-length region was not amplified. The use of
      3' rapid amplification of cDNA ends polymerase chain reaction (3'RACE-PCR) for
      HRT-25 revealed part of intron 3 and an unknown sequence which have not
      identified the HPRT1 gene starting at the 3' end of exon 3. We analyzed HPRT1
      genomic DNA in order to confirm the mutation with the unknown sequence in the
      genomic DNA. Unknown sequence compared through BLAST analysis of human genome
      (NCBI; http://www.ncbi.nlm.nih.gov/BLAST/) showed that at least 0.5 to 0.6-Mb
      telomeric to HPRT1 on chromosome Xq where located near LOC340581. This study
      provides the molecular basis for the involvement of genomic instability in germ
      cells.

PMID- 15571225
TI  - Effects of hypoxanthine on adenosine transport in human lymphocytes. Implications
      in the pathogenesis of Lesch-Nyhan syndrome.
AB  - We have examined the effect of hypoxanthine on adenosine transport and [3H] NBTI
      binding in peripheral blood lymphocytes (PBL) cultures. Pre-incubation with
      hypoxanthine originates a dose dependent decrease of adenosine transport and [3H]
      NBTI binding sites in PBL.

PMID- 15571226
TI  - Hypoxanthine effects on cyclic AMP levels in human lymphocytes.
AB  - We have measured hypoxanthine effect on cAMP levels in PBL in basal conditions
      (no agonist), and with the addition of 2-(p-[2-carboxyethyl] phenylethylamino)-5'
      N-ethylcarboxamidoadenosine (CGS-21680, a specific A2 receptor agonist). We have
      found that hypoxanthine, at 25 microM and 50 microM concentrations, increases
      cAMP levels in PBL in basal and A2 agonist stimulated conditions.

PMID- 15571227
TI  - Nucleotide degradation products in cerebrospinal fluid (CSF) in inherited and
      acquired pathologies.
AB  - CSF purines were grossly elevated compared with controls only in adenylosuccinate
      lyase (ADSL) deficiency and TB meningitis. The former representing low
      permeability, the latter severe damage to the normal blood/brain barrier. By
      contrast, the similarity to controls, with no difference between Lesch-Nyhan
      disease (LND) or LND variants, would exclude hypoxia as a factor in the severe
      neurological deficits in LND. Similar findings in purine nucleoside phosphorylase
      (PNP) deficiency (although nucleosides replace the normal bases) likewise exclude
      hypoxia in the aetiology of the albeit milder neurological deficits.

PMID- 15571228
TI  - Are allopurinol and metabolites found in HPRT deficient erythrocytes responsible
      for increased NAD synthesis?
AB  - Aim of this study was to ascertain whether allopurinol, usually administered to
      hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficient patients, or
      metabolites abnormally increased in HPRT deficient erythrocytes (NAD, PPribP)
      could be directly responsible for the reported increased activities of nicotinic
      acid phosphoribosyltransferase (NAPRT) and NADsynthetase (NADs) in these
      patients. No direct effect of the mentioned metabolites was demonstrated.

PMID- 15571229
TI  - Adenosine transport in HPRT deficient lymphocytes from Lesch-Nyhan disease
      patients.
AB  - We have analysed adenosine transport and [3H] NBTI binding in peripheral blood
      lymphocytes obtained from Lesch-Nyhan patients, in basal conditions and following
      24 h incubation with hypoxanthine. We found that adenosine transport and [3H]
      NBTI binding were significantly decreased in PBL-LN with respect to PBL-C in
      basal conditions. Following 25 microM hypoxanthine incubation, adenosine
      transport is decreased in PBL-LN with respect to basal transport, however, [3H]
      NBTI binding in PBL-LN was not decreased following hypoxanthine incubation.

PMID- 15571230
TI  - The pathophysiology of hyperuricemia in essential hypertension: a pilot study.
AB  - We have examined whether hyperuricemia in essential hypertension may be related
      to an increased insulin secretion thereby enhancing the tubular reabsorption of
      sodium and thus uric acid. Insulin hypersecretion, as elicited by the oral
      glucose tolerance test (OGTT), increased a mean of 5-fold in 12 essential
      hypertensive patients. Urinary uric acid to creatinine ratio significantly
      diminished by a mean of 62% after the OGTT. Simultaneously, urinary sodium to
      creatinine ratio decreased by a mean of 54%. These results suggest that insulin
      may mediate uric acid underexcretion due to its tubular sodium retaining effect
      in essential hypertensive patients.

PMID- 15571231
TI  - Urate oxidation in CSF and blood of patients with inflammatory disorders of the
      nervous system.
AB  - Urate is largely excluded from the brain under non-inflammatory conditions
      (concentration gradient serum:CSF about 10:1), but increases markedly in Guillain
      Barre Syndrome and bacterial meningitis. The oxidation product allantoin is
      normally not passively distributed between blood and cerebrospinal fluid
      (gradient 3:1) and increases 5-fold in CSF of patients with meningitis. Patients
      with multiple sclerosis had normal levels of urate and allantoin in blood and
      CSF.

PMID- 15571232
TI  - Deoxyribonucleoside kinases in mitochondrial DNA depletion.
AB  - Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of
      mitochondrial disorders, manifested by a decreased mtDNA copy number and
      respiratory chain dysfunction. Primary MDS are inherited autosomally and may
      affect a single organ or multiple tissues. Mutated mitochondrial
      deoxyribonucleoside kinases; deoxyguanosine kinase (dGK) and thymidine kinase 2
      (TK2), were associated with the hepatocerebral and myopathic forms of MDS
      respectively. dGK and TK2 are key enzymes in the mitochondrial nucleotide salvage
      pathway, providing the mitochondria with deoxyribonucleotides (dNP) essential for
      mtDNA synthesis. Although the mitochondrial dNP pool is physically separated from
      the cytosolic one, dNP's may still be imported through specific transport. Non
      replicating tissues, where cytosolic dNP supply is down regulated, are thus
      particularly vulnerable to dGK and TK2 deficiency. The overlapping substrate
      specificity of deoxycytidine kinase (dCK) may explain the relative sparing of
      muscle in dGK deficiency, while low basal TK2 activity render this tissue
      susceptible to TK2 deficiency. The precise pathophysiological mechanisms of mtDNA
      depletion due to dGK and TK2 deficiencies remain to be determined, though recent
      findings confirm that it is attributed to imbalanced dNTP pools.

PMID- 15571233
TI  - Thymidine phosphorylase deficiency causes MNGIE: an autosomal recessive
      mitochondrial disorder.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal
      recessive disorder caused by mutations in the gene encoding thymidine
      phosphorylase (TP). The disease is characterized clinically by impaired eye
      movements, gastrointestinal dysmotility, cachexia, peripheral neuropathy,
      myopathy, and leukoencephalopathy. Molecular genetic studies of MNGIE patients'
      tissues have revealed multiple deletions, depletion, and site-specific point
      mutations of mitochondrial DNA. TP is a cytosolic enzyme required for nucleoside
      homeostasis. In MNGIE, TP activity is severely reduced and consequently levels of
      thymidine and deoxyuridine in plasma are dramatically elevated. We have
      hypothesized that the increased levels of intracellular thymidine and
      deoxyuridine cause imbalances of mitochondrial nucleotide pools that, in turn,
      lead to the mtDNA abnormalities. MNGIE was the first molecularly characterized
      genetic disorder caused by abnormal mitochondrial nucleoside/nucleotide
      metabolism. Future studies are likely to reveal further insight into this
      expanding group of diseases.

PMID- 15571234
TI  - Adenylosuccinate lyase deficiency: study of physiopathologic mechanism(s).
AB  - Nucleotide concentrations were normal in adenylosuccinate lyase-deficient
      fibroblasts, and the succinylpurines were not toxic for cultured neuronal cells.

PMID- 15571235
TI  - Adenylosuccinate lyase deficiency--first British case.
AB  - A deficiency of adenylosuccinate lyase (ASDL) is characterised by the
      accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body
      fluids. The severity of the clinical presentation correlates with a low S
      Ado/SAICAr ratio in body fluids. We report the first British case of ADSL
      deficiency. The patient presented at 14 days with a progressive neonatal
      encephalopathy and seizures. There was marked axial and peripheral hypotonia.
      Brain MRI showed widespread white matter changes. She died at 4 weeks of age.
      Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF
      and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The
      patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and
      c.572 C>T (R190X).

PMID- 15571236
TI  - Modulation of glycogen phosphorylase activity affects 5-phosphoribosyl-1
      pyrophosphate availability in rat hepatocyte cultures.
AB  - The effect of modulation of the rate of glycogenolysis on the availability of 5
      phosphoribosyl-1-pyrophosphate (PRPP) was investigated in rat hepatocyte
      cultures. Dibutyryl cyclic AMP (dbcAMP), forskolin and glucagon, activating
      glycogen phosphorylase through activation of protein kinase A (PKA), were found
      to raise PRPP availability by 44%-56%. Arg-vasopressin and phenylephrine,
      activating glycogen phosphorylase through the phosphoinositide cascade, did not
      affect PRPP availability. dbcAMP, but not phenylephrine, increased the
      degradation of pre labeled glycogen by 57%. Caffeine and CP-91149, inhibitors of
      glycogen phosphorylase, decreased PRPP availability by 33% and 43%, respectively.
      The finding that induction of glycogenolysis enhances, and inhibition of
      glycogenolysis decelerates PRPP generation suggests that glycogenolysis is a
      major contributor to PRPP generation in liver tissue in the basal
      (postabsorptive) state.

PMID- 15571237
TI  - Cyclase and phosphodiesterase activity on pre-T lymphoid human cells, treated
      with dimethyl sulfoxide (DMSO).
AB  - Our aim is to estimate the role of the DMSO on pre-T lymphoid human cells, we
      have searched the cyclase and phosphodiesterase activity. We have studied the
      GTPspecific cyclase (G-Case) and have observed an analogous course to that one of
      the cAMP-PDE, where, in both cases, the differences ratio is approximately 5. For
      the cyclase activity values it has been found that cAMP neo formed is
      undeterminable in these cells, for the controls and the treated samples.

PMID- 15571238
TI  - Evaluation of ADA gene expression and transduction efficiency in ADA/SCID
      patients undergoing gene therapy.
AB  - A capillary electrophoresis (CE) method was developed for ADA/SCID diagnosis and
      monitoring of enzyme replacement therapy, as well as for exploring the
      transfection efficiency for different retroviral vectors in gene therapy.

PMID- 15571239
TI  - Urinary methylxanthine and autistic disorder: absence of previously reported
      correlation.
AB  - We were unable to reveal significant difference in the levels of xanthine and
      methylxanthines in the urine samples from 59 patients diagnosed with autistic
      symptoms and 64 age- and sex-matched normal volunteers. Our data suggest that
      abnormalities in xanthine and methylxanthine excretion (US Patent 20020019406 A1,
      Feb. 12, 2002) represent distincly uncommon symptoms in autism.

PMID- 15571240
TI  - Biochemical and molecular genetic correlation in adenylosuccinate lyase
      deficiency.
AB  - An homology model of human adenylosuccinate lyase structure shows that P100A
      substitution distorts the amino acid chain of domain I in the proximity of His
      86, which behaves as general acid in the catalysis, and may expose Cys-98 and Cys
      99 to oxidising agents. This model is in line with the observation that the
      defective protein is strongly inhibited by 4-hydroxy-2-nonenal, an hydroxyalkenal
      that is known to form thio-ether linkage with proteins.

PMID- 15571241
TI  - Identification of the 5'-nucleotidase activity altered in neurological syndromes.
AB  - 5'-Nucleotidases comprise a family of enzymes involved in the regulation of
      intracellular and extracellular nucleotide concentration. There is increasing
      knowledge about an involvement of these activities in the aetiology of
      neurological disorders. In this paper we present a protocol for the
      identification of the altered enzyme in fibroblasts primary culture from patients
      and controls.

PMID- 15571242
TI  - The genetic basis of the interaction between pyrimidine 5' nucleotidase I
      deficiency and hemoglobin E.
AB  - We have previously described a family in which the interaction between pyrimidine
      5' nucleotidase I (P5N-I) deficiency and hemoglobin E resulted in severe
      haemolytic anaemia. In this study we explored the genetic basis of the severe
      clinical phenotype and look for evidence of the interaction between these
      conditions. A P5N-I gene mutation (IVS8 + 1-2delGT) was found in the family,
      confirming that the severe phenotype results from the interaction between two
      genetic diseases.

PMID- 15571243
TI  - Elevated erythrocyte CDP-choline levels associated with beta-thalassaemia in
      patients with transfusion independent anaemia.
AB  - The accumulation of CDP-ethanolamine as well as CDP-choline in a small cohort of
      patients with normal UMPH1 and no defined cause for their anaemia suggested a
      defect in both phosphotransferases. Here we report 10 patients with transfusion
      independent beta-thalassaemia; 8 being pure heterozygotes and 2 heterozygotes
      also for Hb E. Mean CDP-choline (86.xxx +/- 48 microM) and CDP-ethanolamine (34.6
      microM +/- 34.5 microM), mean control <3 microM. Elevated CDP-choline in patients
      with no defined cause for their haemolytic anaemia was previously suggested as a
      possible indicator of CDP-choline phosphotransferase deficiency. Here we
      associate it with transfusion independent beta-thalassaemia.

PMID- 15571244
TI  - Mitochondrial function dependent proliferation assay for the diagnosis of
      mitochondrial disorders in human fibroblasts.
AB  - A media has been developed which enables the assessment of mitochondrial function
      in fibroblasts by measuring proliferation as an end point.

PMID- 15571245
TI  - Severe impairment of nucleotide synthesis through inhibition of mitochondrial
      respiration.
AB  - Since de-novo synthesis of pyrimidine nucleotides is coupled to the mitochondrial
      respiratory chain (RC) via dehydroorotic acid dehydrogenase (DHODH), respiratory
      chain dysfunction should impair pyrimidine synthesis. To investigate this, we
      used specific RC inhibitors, Antimycin A and Rotenone, to treat primary human
      keratinocytes and 143B cells, a human osteosarcoma cell line, in culture. This
      resulted in severe impairment of de novo pyrimidine nucleotide synthesis. The
      effects of RC inhibition were not restricted to pyrimidine synthesis, but
      concerned purine nucleotides, too. While the total amount of purine nucleotides
      was not diminished, they were significantly broken down from triphosphates to
      monophosphates, reflecting impaired mitochondrial ATP regeneration. The effect of
      Rotenone was similar to that of Antimycin A. This was surprising since Rotenone
      inhibits complex I of the respiratory chain, which is upstream of ubiquinone
      where DHODH interacts with the RC. In order to avoid unspecific effects of
      Rotenone, we examined the consequences of a mitochondrial DNA mutation that
      causes a specific complex I defect. The effect was much less pronounced than with
      Rotenone, suggesting that complex I inhibiton cannot fully explain the marked
      effect of Rotenone on pyrimidine nucleotide synthesis.

PMID- 15571246
TI  - Dihydroorotate dehydrogenase mRNA and protein expression analysis in normal and
      drug-resistant cells.
AB  - To follow the expression of the fourth enzyme of pyrimidine de novo synthesis
      dihydroorotate dehydrogenase (DHODH) in cells and tissues, we studied the DHODH
      mRNA expression by means of RT-PCR in rat tissues. Rabbit polyclonal anti-DHODH
      immunoglobulins were applied for immunochemical quantification of the enzyme
      protein by Western blotting. In mouse B-lymphocytes, which were adapted to
      tolerate up to a 50-fold concentration of the DHODH inhibitor leflunomide, a 20
      fold protein overexpression was measured. Southern blotting indicated DHODH gene
      amplification.

PMID- 15571247
TI  - Estrogen attenuates P2X7-R-mediated apoptosis of uterine cervical cells by
      blocking calcium influx.
AB  - Estrogen blocks apoptosis of human ectocervical epithelial cells by modulating
      P2X7/Ca2+ influx. The effect involves decreased Ca2+-influx and cytosolic-calcium
      increase via ATP-activated P2X7 pores. This mechanism may have physiological
      significance in the human cervix, in-vivo, and the results suggest a
      physiological role for estrogen in the cervix as an anti-apoptotic factor.

PMID- 15571248
TI  - Liver transplant: adenosine metabolism and apoptosis.
AB  - Apoptosis and necrosis coexist in ischemia-reperfusion (I/R) injury following
      organ transplant. During experimental liver transplant we evidenced a deep
      alteration in energy and antioxidant status. The activity of purine catabolic
      enzymes was also altered. Caspase-3 (C-3), protein tyrosine phosphatase (PTP)
      showed significative alterations that lead to DNA fragmentation. These findings
      could be of interest in new potential strategy to prevent and treat I/R injury.

PMID- 15571249
TI  - Serum folate and vitamin B12 levels in children from Mozambique.
AB  - In order to investigate the behaviour of biochemical parameters in children from
      Mozambique, we have determined the serum levels of folic acid and vitamin B12,
      two well known markers of nutritional anemia. We have correlated their values
      with other blood parameters and have evidenced potential interesting relationship
      between folate content and platelets count.

PMID- 15571250
TI  - Immucillins as antibiotics for T-cell proliferation and malaria.
AB  - The genetic deficiency of human PNP causes a specific immunodeficiency by
      inducing apoptosis in dividing T-cells. Powerful inhibitors of PNP have been
      designed from the experimental determination of the transition state structure of
      PNPs. The Immucillins are transition state analogue inhibitors with Kd values as
      low as 7 pM. In the presence of deoxyguanosine the Immucillins kill activated
      human T-cells but not other cell types. The Immucillins are orally available and
      of low toxicity to mice. Immucillins also inhibit PNP from Plasmodium falciparum.
      Parasites cultured in human erythrocytes are killed by purine starvation in the
      presence of Immucillins and can be rescued by hypoxanthine.

PMID- 15571251
TI  - New (1-deaza)purine derivatives via efficient C-2 nitration of the (1
      deaza)purine ring.
AB  - Nitration of substituted (1-deaza)purines using a mixture of tetrabutylammonium
      nitrate (TBAN) and trifluoracetic acid anhydride (TFAA) was applied to prepare
      nitrosubstituted (1-deaza)purines at low temperature. The nitro group influences
      the system twofold: 1) it activates other substituents towards nucleophilic
      aromatic substitution and 2) it can be substituted itself leading to a variety of
      di-substituted (1-deaza)purines, also via solid phase syntheses. Several of the
      molecules obtained were studied for their antiprotozoal activity and for
      interactions with the different human adenosine receptors.

PMID- 15571252
TI  - 6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic
      pyrimidine nucleoside phosphonates with antiviral activity.
AB  - Acyclic nucleoside phosphonate derivatives containing a pyrimidine base
      preferably bearing amino groups at C-2 and C-4 (DAPym), and linked at the C-6
      position to (S)-[3-hydroxy-2-(phosphonomethoxy)propoxy] (HPMPO), 2
      (phosphonomethoxy) ethoxy (PMEO) or (R)-[2-(phosphonomethoxy)propoxy] (PMPO),
      display an antiviral sensitivity spectrum that closely mimic that of the parental
      (S)-HPMP-, PME- and (R)-PMP-purine derivatives. Several PMEO-DAPym derivatives
      proved as potent as PMEA (adefovir) and (R)-PMPA (tenofovir) in inhibiting
      Moloney murine sarcoma virus (MSV)-induced tumor formation in newborn NMRI mice.
      The HPMPO-, PMEO- and PMPO-DAPym derivatives represent a novel well-defined
      subclass among the acyclic nucleoside phosphonates endowed with potent and
      selective antiviral activity.

PMID- 15571253
TI  - Antiproliferative activity and mechanism of action of fatty acid derivatives of
      gemcitabine in leukemia and solid tumor cell lines and in human xenografts.
AB  - Gemcitabine is a deoxycytidine analog, which can be inactivated by deamination
      catalyzed by deoxycytidine deaminase (dCDA). Altered transport over the cell
      membrane is a mechanism of resistance to gemcitabine. To facilitate accumulation,
      the fatty acid derivative CP-4125 was synthesized. Since, the fatty acid is
      acylated at the site of action of dCDA, a decreased deamination was expected. CP
      4125 was equally active as gemcitabine in a panel of rodent and human cell lines
      and in human melanoma xenografts bearing mice. In contrast to gemcitabine, CP
      4125 was not deaminated but inhibited deamination of deoxycytidine and
      gemcitabine. Pools of the active triphosphate of gemcitabine increased for over
      20 hr after CP-4125 exposure, while these pools decreased directly after removal
      of gemcitabine. IN CONCLUSION: CP-4125 is an interesting new gemcitabine
      derivative.

PMID- 15571254
TI  - Selective increase of dATP pools upon activation of deoxycytidine kinase in
      lymphocytes: implications in apoptosis.
AB  - Stimulation of the activity of deoxycytidine kinase (dCK), the principal
      deoxynucleoside salvage enzyme, has been recently considered as a protective
      cellular response to a wide range of agents interfering with DNA repair and
      apoptosis. In light of this, the potential contribution of dCK activation to
      apoptosis induction--presumably by supplying dATP or its analogues for the
      apoptosome formation--deserves consideration. Two-hour exposure of human
      tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold
      activation of dCK. This activation process was inhibited by pifithrin-alpha, a
      potent inhibitor of p53. When the dNTP pools were determined, both
      deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments,
      while dATP levels elevated by 62%, 77% and 50% in the CdA, aphidicolin and
      etoposide-treated cells, respectively. We assume that dCK activation elicited by
      cellular damage might be a proapoptotic factor in terms of generating dATP well
      before the release of cytochrome c and deoxyguanosine kinase from mitochondria.

PMID- 15571255
TI  - Fluorescence studies of substrate binding to human recombinant deoxycytidine
      kinase.
AB  - Deoxycytidine kinase (dCK), is responsible for the phosphorylation of
      deoxynucleosides to the corresponding monophosphates using ATP or UTP as
      phosphate donors. Steady-state intrinsic fluorescence measurements were used to
      study interaction of dCK with substrates in the absence and presence of phosphate
      donors. Enzyme fluorescence quenching by its substrates exhibited unimodal
      quenching when excited at 295 nm. Binding of substrates induced conformational
      changes in the protein, suggesting that dCK can assume different conformational
      states with different substrates and may account for the observed differences in
      their specificity. dCK bound the substrates more tightly in the presence of
      phosphate donors and UTP is the preferred phosphate donor. Among the substrates
      tested, the antitumour drugs gemcitabine and cladribine were bound very tightly
      by dCK, yielding Kd values of 0.75 and 0.8 microM, respectively, in the presence
      of UTP.

PMID- 15571256
TI  - Quantitative real time PCR of deoxycytidine kinase mRNA by Light Cycler PCR; in
      relation to enzyme activity.
AB  - Deoxycytidine kinase (dCK) is essential for the phosphorylation of several
      deoxyribonucleosides and various analogues such as gemcitabine (2',2'
      difluorodeoxycytidine). We developed and optimized a sensitive real time Light
      Cycler (LC) PCR assay for dCK with SYBR green detection. The enzymatic activity
      measured in the same human xenografts of dCK correlated excellently with dCK mRNA
      expression levels measured by the LC. This assay can be used for evaluation of
      dCK expression in tumors.

PMID- 15571257
TI  - Immunocytochemical detection of deoxycytidine kinase in pediatric malignancies in
      relation to in vitro cytarabine sensitivity.
AB  - Deoxycytidine kinase (dCK) is essential for the phosphorylation of cytarabine
      (ara-C), a deoxycytidine analog active against acute leukemias. Resistance to ara
      C has been linked to dCK deficiency. In this study we determined the expression
      of the dCK protein in pediatric malignancies, using immunocytochemistry and
      related the expression levels to in vitro ara-C sensitivity (measured with the
      MTT-assay). dCK expression was high in the AML and retinoblastoma samples, in the
      ALL samples dCK expression ranged from low to very high. The brain tumor samples
      expressed low levels of dCK. AML was significantly more sensitive in vitro to ara
      C compared to ALL (p = 0.03). Retinoblastoma and brain tumor cells were extremely
      resistant in vitro, we were unable to detect more than 50% ara-C induced cell
      kill in the majority of samples. Samples were combined in groups according to dCK
      expression. Samples with low dCK expression were significantly more resistant to
      ara-C compared to samples with high dCK expression. In conclusion, dCK expression
      varies between individual samples and between different types of malignancies and
      may play a role in resistance to ara-C in particular tumor types.

PMID- 15571258
TI  - Stimulation of deoxycytidine kinase results in prolonged maintenance of the
      enzyme activity.
AB  - A number of genotoxic and antiproliferative agents such as 2-chlorodeoxyadenosine
      (Cladribine; CdA) and aphidicolin (APC) have been shown to stimulate the activity
      of deoxycytidine kinase, the main deoxynucleoside salvage enzyme in lymphocytes.
      Here we show that enzyme activation could be prevented by treating cells with the
      membrane-permeant calcium chelator BAPTA-AM. Long-term incubations demonstrated
      that CdA and APC not only stimulated but also sustained deoxycytidine kinase
      activity in the cellular context, as compared to the control and BAPTA-AM treated
      enzyme activities.

PMID- 15571259
TI  - New evidences for a regulation of deoxycytidine kinase activity by reversible
      phosphorylation.
AB  - Recent studies indicate that deoxycytidine kinase (dCK), which activates various
      nucleoside analogues used in antileukemic therapy, can be regulated by post
      translational modification, most probably through reversible phosphorylation. To
      further unravel its regulation, dCK was overexpressed in HEK-293 cells as a His
      tag fusion protein. Western blot analysis showed that purified overexpressed dCK
      appears as doublet protein bands. The slower band disappeared after treatment
      with protein phosphatase lambda (PP lambda) in parallel with a decrease of dCK
      activity, providing additional arguments in favor of both phosphorylated and
      unphosphorylated forms of dCK.

PMID- 15571260
TI  - Upregulation of platelet derived endothelial cell growth factor/thymidine
      phosphorylase by interferon alpha.
AB  - Thymidine phosphorylase (TP) catalyzes the phosphorolytic cleavage of thymidine
      to thymine and deoxyribose-1-phosphate. TP, which is overexpressed in a wide
      variety of solid tumors, is involved in the activation and inactivation of
      fluoropyrimidines. TP is known to be regulated by several cytokines and
      interferons. In our HT29 cell line the TP mRNA and activity expression increased
      2-3 fold after treatment with interferon alpha.

PMID- 15571261
TI  - Pyrimidine degradation defects and severe 5-fluorouracil toxicity.
AB  - 5-Fluorouracil (5FU) remains one of the most frequently prescribed
      chemotherapeutic drugs for the treatment of cancer. Recently, the pivotal role of
      the catabolic pathway of 5FU in the determination of toxicity towards 5FU has
      been highlighted. Patients with a (partial) dihydropyrimidine dehydrogenase
      deficiency proved to be at risk of developing severe toxicity after the
      administration of 5FU. A partial dihydropyrimidinase deficiency proved to be a
      novel pharmacogenetic disorder associated with severe 5FU toxicity.

PMID- 15571262
TI  - Thymidylate synthase polymorphism and microsatellite instability: association in
      colorectal cancer.
AB  - 5-Fluorouracil (5FU) is the main drug used for the treatment of colorectal cancer
      (CRC) and Thymidilate Synthase (TS) is its target enzyme. TS gene has regulatory
      tandemly repeated sequences in its 5' and 3'untraslated region (5'-3' UTR). CRC
      often shows a kind of genomic instability called Microsatellite Instability (MSI)
      that is associated with TS levels and survival. Our data show that the genotype
      2R/2R (homozygosity for 2 tandem repeat sequences in the 5'UTR) is more
      frequently associated with MSI+ and lower TS levels. More over we did not find
      any significant association between the 2R/3R (heterozygosity for 2 and 3 tandem
      repeat sequences in the 5'UTR) and 3R/3R (homozygosity for 3 tandem repeat
      sequences in the 5' UTR) genotypes with the MSI+ and MSI-, while these genotypes
      were associated with a higher TS expression. As a consequence we can hypothesise
      that patients bearing CRC with the MSI+, the 2R/2R genotype and with low TS
      levels could have a better prognosis and they could not be drug resistant.

PMID- 15571263
TI  - Polymorphism of the thymidylate synthase gene and thymidylate synthase levels in
      colon cancer cell lines and different tissues of colorectal cancer patients.
AB  - In a panel of 18 colon cancer cell lines we found that the thymidylate synthase
      (TS) genotype was related to TS enzyme activity, but not to TS protein and mRNA
      levels. In addition, no relation with drug sensitivity was observed. TS
      genotyping of different tissues from 78 colorectal cancer patients revealed a
      high level of homology in polymorphic status between normal and malignant tissues
      and the heterozygous genotype to be the most frequent.

PMID- 15571264
TI  - The clinical impact of thiopurine methyltransferase polymorphisms on thiopurine
      treatment.
AB  - Acute lymphoblastic leukaemia (ALL) is the most common malignancy of childhood.
      Although current treatment results in long term survival in over 70% of cases
      there is evidence that as many as 50% could have been cured using a less complex
      regimen with a lower incidence of long term side effects. In previous studies it
      has been found that thiopurines given as part of continuing therapy are key
      agents in preventing relapse. However, optimal administration during continuing
      therapy is often not achieved. Variation in the level of thiopurine
      methyltransferase (TPMT) activity appears to be a major molecular determinant of
      the extent of thiopurine metabolism. TPMT activity shows a trimodal distribution
      pattern. A lack of activity is found in approximately one in 300 Caucasians;
      approximately 11% have intermediate activity and the remaining 89% high activity.
      Congenital loss of activity is associated with grossly elevated levels of active
      drug and profound myelosuppression on exposure to thiopurines. This loss of
      activity has been attributed to single nucleotide polymorphisms (SNPs) within the
      TPMT gene. The frequency of SNPs is related to ethnicity, with the most common in
      Caucasians being TPMT*3A which is characterized by a G to A transition at
      position 460 with a substitution of alanine for tyrosine at amino acid 154
      (A154Y) and a transition of A to G at nucleotide 719 resulting in a change of
      tyrosine to cysteine at position 240 (Y240C). Polymorphisms have also been
      identified within the 5' flanking promoter region of the TPMT gene due to a
      variable number of tandem repeats (VNTR*3-*8). An overview of the polymorphisms
      identified to date, their implication on the metabolism of the thiopurine drugs
      and therapeutic importance will be discussed.

PMID- 15571265
TI  - Mutation in the ITPA gene predicts intolerance to azathioprine.
AB  - Inosine triphosphate pyrophosphatase (ITPase) deficiency occurs with polymorphic
      frequencies in Caucasians and results in the benign accumulation of the inosine
      nucleotide ITP. In 62 patients treated with azathioprine for inflammatory bowel
      disease, the ITPA 94C>A deficiency-associated allele was significantly associated
      with adverse drug reactions (OR 4.2, 95% CI 1.6-11.5, p = 0.0034). Significant
      associations were found for flu-like symptoms (OR 4.7, 95% CI 1.2-18.1, p =
      0.0308), rash (OR 10.3, 95% CI 4.7-62.9, p = 0.0213) and pancreatitis (OR 6.2, CI
      1.1-32.6, p = 0.0485). Polymorphism in the ITPA gene thus predicts AZA
      intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine,
      should be considered for AZA-intolerant patients with ITPase deficiency.

PMID- 15571266
TI  - Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a
      Japanese population.
AB  - The enzyme inosine triphosphate pyrophosphatase (ITPase) catalyses the
      pyrophosphohydrolysis of ITP to IMP. ITPase deficiency is a clinically benign
      autosomal recessive condition characterised by the abnormal accumulation of ITP
      in erythrocytes. A deficiency of ITPase may predict adverse reactions to therapy
      with the thiopurine drug 6-mercaptopurine and its prodrug azathioprine. In this
      study, we examine the frequencies of ITPA polymorphisms in 100 healthy Japanese
      individuals. The allele frequency of the 94C > A variant in the Japanese sample
      was 0.135 (Caucasian allele frequency 0.06). The IV2 + 21A > C polymorphism was
      not found in Japanese (Caucasian allele frequency 0.130). Allele frequencies of
      the 138G > A, 561G > A and 708G > A polymorphisms were 0.57, 0.18 and 0.06
      respectively in the Japanese population, and with the exception of the 138G > A
      polymorphism, similar to allele frequencies in Caucasians.

PMID- 15571267
TI  - Genetic determinants of the pre- and post-azathioprine therapy thiopurine
      methyltransferase activity phenotype.
AB  - Thiopurine drug therapy has been reported to lead to a variable increase in red
      cell TPMT activity that may alter effective dose and therapeutic outcome. The aim
      of this study was to correlate Variable Number Tandem Repeat (VNTR) in the
      promoter region of the TPMT gene with induction of red cell TPMT activity in
      patients treated with azathioprine (AZA). In 58 patients, TPMT activity measured
      at 3 months was not significantly induced on average above pre-therapy levels.
      Individual patients showed variation in TPMT activity pre- and post-AZA therapy,
      however changes in TPMT activity were not predicted by VNTR configuration. In
      conclusion, TPMT promoter VNTRs are unlikely to play a significant role in
      changes in TPMT activity in response to AZA therapy.

PMID- 15571268
TI  - GTP concentrations are elevated in erythrocytes of renal transplant recipients
      when conventional immunosuppression is replaced by the inosine monophosphate
      dehydrogenase inhibitor mycophenolic acid mofetil (MMF).
AB  - We show that GTP concentrations rise in the erythrocytes of renal transplant
      recipients receiving the immunosuppressant MMF, and demonstrate that this effect
      is not caused by poor renal function after engraftment. We propose a model that
      is consistent with our observations.

PMID- 15571269
TI  - Novel mutations and hot-spots in patients with purine nucleoside phosphorylase
      deficiency.
AB  - Purine nucleoside phosphorylase (PNP) deficiency results in severe immune
      dysfunction and early death from infections. Lymphopenia, reduced serum uric
      acid, and abnormal PNP enzymatic activity assist in the diagnosis of PNP
      deficient patients. Analysis of the gene encoding PNP in these patients reveals
      several recurring mutations. Identification of these hot-spots for mutation may
      allow faster confirmation of the diagnosis in suspected cases.

PMID- 15571270
TI  - Clofarabine in adult acute leukemias: clinical success and pharmacokinetics.
AB  - Clofarabine is a deoxyadenosine analog synthesized with the intention of
      retaining the favorable mechanistic properties of fludarabine and cladribine
      while eliminating their undesirable characteristics. Phase I studies among 32
      patients with acute leukemia defined a maximum tolerated dose (MTD) of 40 mg/m2/d
      given as a one hour infusion daily for 5 days. The dose limiting toxicity (DLT)
      was transient hepatotoxicity. In a phase II study, 62 patients with acute
      leukemias received clofarabine at the MTD over 1 hour daily for 5 days. Twenty
      patients (32%) achieved complete response (CR), 1 had a partial response (PR),
      and 9 had a CR but without platelet recovery (CRp), for an overall response rate
      of 48%. Pharmacokinetic studies in the phase I trial revealed marked
      heterogeneity in peak levels of clofarabine among patients at the end of
      infusion, however; there was a linear, dose dependent increase in clofarabine
      concentration in the plasma. Pharmacodynamically, at the MTD, DNA synthesis was
      inhibited by more than 80% at the end of infusion. In phase II studies, the
      relationship between the pharmacokinetics of clofarabine triphosphate
      accumulation and clinical response at the MTD was explored, revealing an
      accumulation advantage of the cytotoxic triphosphate in leukemia cells of
      responders. The circulating leukemia blasts of patients who respond to
      clofarabine therapy exhibited a favorable pharmacokinetic profile. In conclusion,
      clofarabine is an active agent in the treatment of acute leukemias and MDS, and
      cellular pharmacokinetics has prognostic significance.

PMID- 15571271
TI  - Effects of 2-chloro-2'-deoxyadenosine on the cell cycle in the human leukemia
      EHEB cell line.
AB  - To explain why 2-chloro-2'-deoxyadenosine (CdA) is unable to block DNA synthesis
      and cell cycle progression, and paradoxically enhances progression from G1 into S
      phase in the CdA-resistant leukemia EHEB cell line, we studied its metabolism and
      effects on proteins regulating the transition from G1 to S phase. A low
      deoxycytidine kinase activity and CdATP accumulation, and a lack of p21 induction
      despite p53 phosphorylation and accumulation may account for the inability of CdA
      to block the cell cycle. An alternative pathway involving pRb phosphorylation
      seems implicated in the CdA-induced increase in G1 to S phase progression.

PMID- 15571272
TI  - Management of hyperuricemia with rasburicase review.
AB  - Tumor lysis syndrome (TLS) is a serious complication in patients with
      hematological malignancies. Massive lysis of tumor cells can lead to
      hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia. These metabolic
      disturbances may result in renal failure, because of precipitation of uric acid
      crystals and calcium phosphate salts in the kidney. The standard prophylaxis or
      treatment of hyperuricemia consists of decreasing uric acid production with
      allopurinol and facilitating its excretion by urinary alkalinization and
      hyperhydration. By inhibiting the enzyme xanthine oxidase, allopurinol blocks the
      conversion of hypoxanthine and xanthine into uric acid. An alternative treatment
      is urate oxidase which oxidates uric acid into allantoin. Allantoin is 5-10 times
      more soluble than uric acid and is therefore excreted easily. In several clinical
      trials rasburicase, the recombinant form of urate oxidase, has shown to be very
      effective in preventing and treating hyperuricemia. Rasburicase, in contrast with
      the non-recombinant form of urate oxidase uricozyme, is associated with a low
      incidence of hypersensitivity reactions. In addition to the demonstrated clinical
      benefit, rasburicase also proved to be a cost-effective option in the management
      of hyperuricemia.

PMID- 15571273
TI  - Selective transport of a new class of purine antimetabolites by the protozoan
      parasite Trypanosoma brucei.
AB  - Purine antimetabolites have been very successful therapeutic agents against a
      host of infectious diseases and malignancies. Success of the treatment relies as
      much on the efficient accumulation by the target cell or organism as it does on
      selective action on a vital biochemical pathway of the target cell. Here we
      compare the ability of a new class of tricyclic purine antimetabolites to
      interact with transporters from human erythrocytes or Trypanosoma brucei. We show
      that these compounds display a remarkable selectivity for the parasite's
      transporters. The adenine analogue showed greater trypanocidal activity than the
      hypoxanthine or guanine analogues in vitro.

PMID- 15571274
TI  - Regulation of equilibrative nucleoside uptake by protein kinase inhibitors.
AB  - The uptake of nucleosides and nucleoside analogs into human leukemia K562 cells
      is facilitated by the equilibrative transporters ENT1 and ENT2. Incubation of
      K562 cells with a variety of protein kinase inhibitors inhibited the transport of
      both uridine (ARA-C) and cytidine (CPEC) analogs. These inhibitory effects were
      observed for a large number of kinase inhibitors including those against p38
      MAPK, the EGF receptor kinase, protein kinase C, TOR and others. Thus these
      results suggest that the nucleoside transporters are unexpected targets for
      kinase inhibitors and may influence the design and application of combinatorial
      approaches of nucleoside analogs and kinase inhibitors in clinical applications.

PMID- 15571275
TI  - Online fluorescent method to assess BCRP/ABCG2 activity in suspension cells.
AB  - An online method was developed to monitor BCRP mediated efflux of fluorescent
      substrates in suspension cells. To this end, a 2-compartment system consisting of
      a transwell cup and a cuvette was used. In this system we were able to observe
      differences in efflux kinetics between BCRP overexpressing RPMI 8226/MR cells and
      parental myeloid RPMI 8226(s) cells using only 50,000 cells per experiment.
      8226/MR cells displayed a larger cellular efflux rate of the BCRP substrate
      Hoechst 33342, as compared to the wildtype cells. This difference in efflux rate
      was completely decreased in the presence of the BCRP inhibitor Ko143.

PMID- 15571276
TI  - Metabolism of adenosine in human colorectal tumour.
AB  - The aim of this work is to analyse the activities of the enzymes metabolising
      adenosine in fragments of neoplastic and normal-appearing mucosa, surrounding the
      tumour in 20 patients affected by colorectal cancer. The results show that the
      activities of the enzymes are markedly higher in tumour in comparison to normal
      mucosa to coope with the accelerated purine metabolism in cancerous tissues.

PMID- 15571277
TI  - Cloning and expression of malarial pyrimidine enzymes.
AB  - We have cloned genes encoding three enzymes of the de novo pyrimidine pathway
      using genomic DNA from Plasmodium falciparum and sequence information from the
      Malarial Genome Project. Genes encoding dihydroorotase (reaction 3), orotate
      phosphoribosyltransferase (reaction 5), and OMP decarboxylase (reaction 6) have
      been cloned into the plasmid pET 3a or 3d with a thrombin cleavable 9xHis tag at
      the C-terminus and the enzymes were expressed in Escherichia coli. To overcome
      the toxicity of malarial OMP decarboxylase when expressed in E. coli, and the
      unusual codon usage of the malarial gene, a hybrid plasmid, pMICO, was
      constructed which expresses low levels of T7 lysozyme to inhibit T7 RNA
      polymerase used for recombinant expression, and extra copies of rare tRNAs.
      Catalytically-active OMP decarboxylase has been purified in tens of milligrams by
      chromatography on Ni-NTA. The gene encoding orotate phosphoribosyltransferase
      includes an extension of 66 amino acids from the N-terminus when compared with
      sequences for this enzyme from other organisms. We have found that other
      pyrimidine enzymes also contain unusual protein inserts. Milligram quantities of
      pure recombinant malarial enzymes from the pyrimidine pathway will provide
      targets for development of novel antimalarial drugs.

PMID- 15571278
TI  - Down-regulation of human deoxyuridine triphosphate nucleotidohydrolase (dUTPase)
      using small interfering RNA (siRNA).
AB  - A small interfering double stranded RNA molecule (siRNA, 21 bp) corresponding to
      a portion (nucleotides 337 to 357) of domain 3 of the human dUTPase was
      synthesized and used to determine whether it could down-regulate dUTPase activity
      in human cells. Transfection of the siRNA into HeLa and HT29 cells resulted in a
      56 +/- 3.6% decrease in dUTPase activity, while transfection of SW620 cells
      resulted in a 27 +/- 6% decrease in dUTPase activity when compared to non-treated
      controls.

PMID- 15571279
TI  - Comparison of mRNA expression levels determined with TaqMan and competitive
      template RT-PCR.
AB  - Two methods for measurement of thymidylate synthase (TS) and dihydropyrimidine
      dehydrogenase (DPD) mRNA expression were compared. Although the relative mRNA
      levels compared to beta-actin measured with competitive template RT-PCR were
      different from the data obtained with a TaqMan based PCR, a significant
      correlation between the two assays was found.

PMID- 15571280
TI  - Mechanistic studies of dUTPases.
AB  - The essential enzyme dUTPase is responsible for preventive DNA repair via
      exclusion of uracil. Lack or inhibition of the enzyme induces thymine-less cell
      death in cells performing active DNA synthesis, serving therefore as an important
      chemotherapeutic target. In the present work, employing differential circular
      dichroism spectroscopy, we show that D. mel. dUTPase, a recently described
      eukaryotic model, has a similar affinity of binding towards alpha,beta-imino-dUTP
      as compared to the prokaryotic E. coli enzyme. However, in contrast to the
      prokaryotic dUTPase, the nucleotide exerts significant protection against tryptic
      digestion at a specific tryptic site 20 A far from the active site in the fly
      enzyme. This result indicates that binding of the nucleotide in the active site
      induces an allosteric conformational change within the central threefold channel
      of the homotrimer exclusively in the eukaryotic enzyme. Nucleotide binding
      induced allosterism in the D. mel. dUTPase, but not in the E. coli enzyme, might
      be associated with the altered hydropathy of subunit interfaces in these two
      proteins.

PMID- 15571281
TI  - A non-radioactive sensitive assay to measure 5-fluorouracil incorporation into
      DNA of solid tumors.
AB  - A non-radioactive method to determine 5-Fluorouracil (5FU) incorporation into DNA
      has been developed. Isolated DNA was enzymatically degraded to bases and the
      resulting 5FU was measured with standard gas-chromatography coupled to mass
      spectrometry (GC-MS) and compared with that of radioactive 5FU in a cell line.
      Incorporation into DNA of the murine Colon 26-B tumor treated with maximal
      tolerated doses of 5FU and fluorodeoxyuridine (FUdR) was maximal after 2 hour and
      was 15.4 and 71.0 fmol/microg DNA, respectively. After a plateau for about 3 days
      a decrease was observed to +/- 2 fmol/microg DNA after 10 days. The assay is very
      sensitive and reproducible and can be used in a clinical setting.

PMID- 15571282
TI  - Role of platelet derived endothelial cell growth factor/thymidine phosphorylase
      in fluoropyrimidine sensitivity and potential role of deoxyribose-1-phosphate.
AB  - Thymidine phosphorylase (TP) catalyzes the phosphorolytic cleavage of thymidine
      (TdR) to thymine and deoxyribose-1-phosphate (dR-1-P). TP, which is overexpressed
      in a wide variety of solid tumors, is involved in the activation and inactivation
      of fluoropyrimidines. We investigated the role of TP in 5'-deoxy-5-fluorouridine
      (5'DFUR), 5-fluorouracil (5FU) and trifluorothymidine (TFT) sensitivity. TP had
      no effect on TFT while it activated 5'DFUR and to a lesser extent 5FU. In order
      to provide an explanation for this difference in activation of 5'DFUR and 5FU, we
      studied the role of the 5FU co-substrate, dR-1-P, needed for its activation.

PMID- 15571283
TI  - Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A
      cells.
AB  - Trifluorothymidine (TFT) can be phosphorylated by thymidine kinase (TK) to TFTMP
      which can inhibit thymidylate synthase (TS), resulting in depletion of thymidine
      nucleotides. TFT can be degraded by thymidine phosphorylase (TP) which can be
      inhibited by thymidine phosphorylase inhibitor (TPI). Using the TS in situ
      Inhibition Assay (TSIA) FM3A breast cancer cells were exposed 4 h or 24 h to TFT
      and 5-Fluorouracil (5FU). TS activity reduced to 9% (0.1 microM TFT) and 58% (1
      microM 5FU) after 4 h exposure and to 6% (TFT) and 21% (5FU) after 24 h exposure.
      TPI did not affect TS inhibition by TFT. FM3A cells lacking TK or TS activity
      (FM3A/TK-) were far less sensitive to TFT compared to FM3A cells. CONCLUSION: TFT
      can be taken up and activated very rapidly by FM3A cancer cells, probably due to
      favourable TK enzyme properties, and TPI did not influence this.

PMID- 15571284
TI  - 5-Fluoro-2'-deoxyuridine has effects on mitochondria in CEM T-lymphoblast cells.
AB  - Fluoropyrimidines are useful anticancer agents and the compound 5-fluoro-2'
      deoxyuridine (FdUrd) plays an important role in chemotherapy of colon cancers.
      Several nucleoside analogs, such as 3'-azido-2',3'-dideoxythymidine (AZT) and
      2',3'-dideoxycytidine (ddC), can be incorporated into and cause depletion of
      mitochondrial DNA (mtDNA). These drugs are known to cause mitochondrial toxicity
      after prolonged treatment in patients. In this study we demonstrate that FdUrd
      reduces the mtDNA content and the expression level of the mtDNA encoded
      cytochrome c oxidase (COX II) in a CEM T-lymphoblastic cell line.

PMID- 15571285
TI  - Effect of fluoropyrimidines on the growth of Ureaplasma urealyticum.
AB  - In the present study, we investigated the effect of fluoropyrimidines on the
      growth of Ureaplasma urealyticum. Addition of fluoropyrimidines strongly
      inhibited bacterial growth. Growth inhibition by these analogues could be
      reversed by addition of either thymidine or deoxyuridine, suggesting inhibition
      of thymidylate biosynthesis as the mechanism in operation.

PMID- 15571286
TI  - Combinations of 5-fluorouracil with UCN-01 or staurosporine.
AB  - The action of 5-Fluorouracil (5-FU) is mediated by inhibition of thymidylate
      synthase (TS), which is regulated by cell cycle proteins controlled by protein
      phosphorylation. We studied the effects of staurosporine and its analogue UCN-01,
      inhibitors of protein kinase C (PKC) on 5-FU cytotoxicity in Lovo colon cancer
      cells. Each drug contributes equally to the cell cycle effects of the 5-FU
      combinations. In sequential drug administration, the cell cycle distribution was
      determined by the first drug. Simultaneous 5-FU combinations induced additive
      effects in induction of apoptosis. When staurosporine was used as the second
      drug, induction of apoptosis was 2-fold higher than the sum of both drugs alone.
      Based on induction of apoptosis 5-FU addition prior to the PKC inhibitors seemed
      preferable.

PMID- 15571287
TI  - Cytotoxic and apoptotic effects of novel heterodinucleoside phosphates consisting
      of 5-fluorodeoxyuridine and Ara-C in human cancer cell lines.
AB  - In search for possible alternatives in the treatment of human malignancies we
      investigated several new heterodinucleoside phosphates consisting of 5
      Fluorodeoxyuridine (5-FdUrd) and Arabinofuranosylcytosine (Ara-C). We show that
      all dimers tested inhibited the number of colonies of CCL228, CCL227, 5-FU
      resistant CCL227 and HT-29 human colon tumor cells with IC50 values ranging from
      0.65 to 1 nM. Dimer # 2 inhibited the number of sensitive and Ara-C resistant H9
      human lymphoma cells with IC50 values ranging from 200 to 230 nM. Since no
      significant difference in the cytotoxicity of the dimers could be observed
      between sensitive and resistant cells, these compounds might be used in the
      treatment of 5-FU and Ara-C resistant tumors.

PMID- 15571288
TI  - Modulation of cytarabine induced cytotoxicity using novel deoxynucleoside analogs
      in the HL60 cell line.
AB  - In order to enhance the cytotoxicity of ara-C in the HL60 cell line the following
      deoxynucleoside analogs were used: cladribine, fludarabine and gemcitabine. HL60
      cells were co-incubated with ara-C and each of the modulators at the ratios of
      their respective IC50s. Cytotoxicity was determined with the MTT-assay and drug
      interactions were evaluated with the combination index (CI) method (Calcusyn;
      Chou & Talalay). CI < 1, CI +/- 1 and > 1 indicate synergism, additive effect and
      antagonism, respectively. We observed moderate synergism between ara-C/cladribine
      and ara-C/gemcitabine, with CIs of 0.76 +/- 0.14 and 0.82 +/- 0.04, respectively.
      The interaction between ara-C/fludarabine resulted in moderate antagonism (CI =
      1.29 +/- 0.11). In conclusion, in this in vitro study we showed that the
      cytotoxicity of ara-C can be succesfully modulated in the HL60 cell line by
      cladribine and gemcitabine.

PMID- 15571289
TI  - Increased cytotoxicity of 2',2'-difluoro-2'-deoxycytidine in human leukemic cell
      lines after a preincubation with cyclopentenyl cytosine.
AB  - The in vitro modulating effect of Cyclopentenyl cytosine (CPEC) on the metabolism
      of gemcitabine was studied in lymphocytic and myeloid leukemic cell-lines. In
      MOLT-3 cells, that were pretreated with CPEC, the incorporation of 2',2'-difluoro
      2'-deoxycytidine triphosphate (dFdCTP) into DNA was significantly increased by 57
      99% in comparison with cells that were only treated with gemcitabine. The
      increased incorporation of dFdCTP into DNA in CPEC pretreated cells was
      paralleled by an increase in apoptotic and necrotic cells of 17-34%. In HL-60
      cells that were preincubated with CPEC, increased concentrations of the mono-/di-
      and triphosphate form of gemcitabine were observed, as well as an increased
      incorporation of dFdCTP into DNA (+773%). This increased incorporation was
      paralleled by a significant increase in apoptosis and necrosis. We conclude that
      CPEC enhances the incorporation of dFdCTP into DNA and thus increases the
      cytotoxicity of gemcitabine in lymphocytic and myeloid leukemic cell-lines.

PMID- 15571290
TI  - Antiproliferative activity and mechanism of action of fatty acid derivatives of
      arabinosylcytosine (ara-C) in leukemia and solid tumor cell lines.
AB  - Resistance to, the hydrophilic drug ara-C, might be meditated by decreased
      membrane transport. Lipophilic prodrugs were synthesized to facilitate uptake.
      These compounds were equally active as ara-C, while the compounds with the
      shortest fatty-acid group and highest number of double bonds were the more
      active. These compounds also show a better retention profile, their effect is
      retained longer than for ara-C.

PMID- 15571291
TI  - Investigation of the substrate recognition of Drosophila melanogaster nucleoside
      kinase by site directed mutagenesis.
AB  - The deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) has a broad
      substrate specificity and a higher catalytic rate than other known
      deoxyribonucleoside kinases. Therefore it is a natural candidate for possible use
      as a suicide gene in combined gene/chemotherapy of cancer. We have performed site
      directed mutagenesis and tested different truncated forms of the enzyme in order
      to increase the affinity for ganciclovir.

PMID- 15571292
TI  - Combination chemotherapy of BCNU and Didox acts synergystically in 9L glioma
      cells.
AB  - Compounds inhibiting DNA repair and synthesis are expected to act synergistically
      with BCNU, a standard agent in the therapy of glioblastoma multiforme, and
      improve survival of patients with malignant gliomas. Ribonucleotide reductase
      (EC1.17.4.1; RR) catalyzes the rate-limiting step in DNA synthesis and plays a
      critical role in maintaining crucial substrates for DNA repair. We have studied
      the effects of Didox, an inhibitor of RR on 9L glioma cells in combination with
      BCNU. We analyzed intracellular dNTP pools and found that Didox significantly
      depleted the intracellular dNTP concentrations. Experiments using cytotoxicity,
      growth inhibition and clonogenic assays showed significant synergism of Didox and
      BCNU. Combination regimens using synchronous administration demonstrated highest
      cytotoxicity. We have also identified altered gene expression in a number of DNA
      repair related enzymes after BCNU treatment using large-scale cDNA arrays. The
      coadministration with Didox could reverse the expression of some of the
      overexpressed repair gene suggesting possible pathways to circumvent the
      developing resistance in 9L glioma cells against BCNU. These results introduce
      the combination of Didox and BCNU as a viable alternative for the treatment of
      malignant gliomas.

PMID- 15571293
TI  - Comparative immunologic and kinetic evaluation of AMP-deaminase isolated from
      normal human liver and hepatocellular carcinoma (HCC).
AB  - In the present paper physico-chemical properties of AMP-deaminase purified from
      human liver neoplasm-hepatocellular carcinoma (HCC) were investigated and
      compared with these obtained for the enzyme from normal, unaffected tissue.

PMID- 15571294
TI  - Amidox, an inhibitor of ribonucleotide reductase, potentiates the action of Ara-C
      in HL-60 human promyelocytic leukemia cells.
AB  - Amidox (3,4-dihydroxybenzamidoxime), a new polyhydroxy-substituted benzoic acid
      derivative, is a potent inhibitor of the enzyme ribonucleotide reductase (RR),
      which catalyses the de novo synthesis of DNA. RR is considered to be an excellent
      target for cancer chemotherapy. In the present study we investigated the
      antineoplastic effects of Amidox alone and in combination with
      Arabinofuranosylcytosine (Ara-C) in HL-60 human promyelocytic leukemia cells. In
      growth inhibition experiments Amidox yielded an IC50 of 30 microM, colony
      formation was inhibited at an IC50 of 20 microM as determined by a soft agar
      assay. Exposure of the cells to 75 and 100 microM Amidox for 24 hours was shown
      to significantly decrease intracellular dCTP, dGTP and dATP pools, whereas dTTP
      concentration increased, as determined by HPLC. The combination of Amidox with
      Ara-C yielded more than additive cytotoxic effects both in growth inhibition
      assays and in soft agar assays. We could show that--after preincubating the cells
      with 75 and 100 microM Amidox and subsequent exposure to Ara-C--intracellular Ara
      CTP levels increased by 576% and 1143%, respectively. In conclusion, Amidox might
      offer an additional option for the treatment of leukemia and thus be further
      investigated in vitro and in vivo.

PMID- 15571295
TI  - Potential role of mycophenolate mofetil in the management of neuroblastoma
      patients.
AB  - In human neuroblastoma cell lines (LAN5, SHEP and IMR32), mycophenolic acid (MPA)
      at concentrations (10(-7)-10(-6) M) readily attainable during immunosuppressive
      therapy with mycophenolate mofetil (Cellcept), induces guanine nucleotide
      depletion leading to cell cycle arrest and apoptosis through a p53 mediated
      pathway (up-regulation of p53, p21 and bax and down-regulation of bcl-2 and
      survivin). MPA-induced apoptosis is also associated to a marked decrease of p27
      protein. In the same cell lines MPA, at lower concentrations (50 nM),
      corresponding to the plasma levels of the active free drug during Cellcept
      therapy, induces differentiation toward the neuronal phenotype by causing a
      partial chronic guanine nucleotide depletion. MPA-induced differentiation is not
      associated to p27 accumulation as occurs using retinoic acid. At a fixed
      concentration of MPA a higher percentage of apoptotic or differentiated cells is
      obtained when non dialysed serum substitutes for the dialysed one, due to the
      higher hypoxanthine concentration in the former (about 10 microM) leading to
      competition on HPRT-mediated salvage of guanine. At hypoxanthine or oxypurinol
      concentrations higher than 1 microM (up to 100 microM) no further enhancement of
      MPA effects was obtained, in agreement with the recently described safety of the
      allopurinol-mycophenolate mofetil combination in the treatment of hyperuricemia
      of kidney transplant recipients. The apoptotic effects of MPA do not appear to be
      significantly increased by the UDP-glucuronosyltransferase inhibitor niflumic
      acid.

PMID- 15571296
TI  - Cyclic nucleotides and neuroblastoma differentiation.
AB  - We have shown that intracellular cGMP levels increase during retinoic acid- and
      mycophenolic acid-induced neuroblastoma differentiation and that a 6 days
      treatment with 1 mM dbcGMP lead LAN5 cell to elaborate a network of neuritic
      processes suggesting an involvement of cGMP in neuroblastoma differentiation. We
      have also investigated the effects of some specific inhibitors of
      phosphodiesterases (PDE1, PDE3, PDE4 and PDE5) on human neuroblastoma (LAN5 and
      SHEP) growth and differentiation. After six days of incubation in the presence of
      each specific inhibitor at 10 x IC50 levels a cytostatic and differentiating
      effect was only observed with the PDE5 inhibitors Zaprinast and MY-5445. The
      cytostatic effect of these compounds increased increasing their concentrations
      far above their IC50 levels for PDE5, suggesting that these compounds could act
      by interfering with other molecular events than direct cGMP-PDE inhibition. No
      appreciable effect was observed using Dipyridamole, another specific PDE5
      inhibitor.

PMID- 15571297
TI  - Cyclic guanosine monophosphate role in human carcinoma pathogenesis.
AB  - In order to examine the cyclic nucleotides (cGMP) role in carcinoma growth and
      invasivity. We analyzed two cell lines, LSHT29 and 17GT, and tissues in patients
      with carcinoma and malignant tissues with (N+) and without (N-) lymph node
      metastases. Higher cGMP levels in pathological samples suggest a strong
      correlation between intracellular cGMP concentration and carcinoma progression.

PMID- 15571298
TI  - [Special issue: the reports presented during the 5th Parkinson's Physicians'
      Symposium].

PMID- 15571299
TI  - [CME-ECG 2].

PMID- 15571300
TI  - [What is your diagnosis? Osseous metastasis in the left knee].

PMID- 15571301
TI  - [Are there innovations in the treatment of Parkinson's disease?].
AB  - In the group of medication acting on the dopaminergic system the transdermal
      application of a dopamine agonist (Rotigotine) and a new MAO B inhibitor
      (Rasigiline) are receiving most attention. With some concern we had to learn that
      pergolide, a potent dopamine agonist, may be the cause of clinically relevant
      valvulopathies. Our possibilities to act on non-dopaminergic deficits is still
      very limited. The studies demonstrating a positive effect of cholinesterase
      inhibitors on cognitive decline are at least a positive signal.

PMID- 15571302
TI  - [Differential therapy of advanced Parkinson's disease with special reference to
      complementary therapeutic approaches].
AB  - In Parkinson's disease advanced symptoms (fluctuation, dyskinesia) and/or
      psychiatric side-effects of medication require a very individual and often
      complicated therapeutic regime. All pharmacological groups can be useful. The
      adjustment of medication needs clinical control, especially when psychiatric
      symptoms occur. Ideally, this task should be left to specially trained medical
      staff. Moreover, there are a number of complementary strategies recommended by
      various suppliers. Physiotherapy, speech therapy and ear acupuncture have in the
      past been shown to be useful even in advanced cases. The German Parkinson Society
      (dPV) has supported clinical trials in respect of the application of ear
      acupuncture, Qigong and the coenzyme Q10. Positive results are expected from Q10.
      Acupuncture cannot be recommended, while Qigong may be helpful for some patients.

PMID- 15571303
TI  - [Surgical therapy of Parkinson's disease].
AB  - For patients with Parkinson's disease with disabling motor fluctuations,
      dyskinesias or tremor, stereotactic neurosurgery can be a valid therapeutic
      option. The following lecture will discuss the historical background of
      stereotactic neurosurgery, possible targets and stereotactic procedures
      (lesioning vs deep brains stimulation), as well as, the need for a
      multidisciplinary assessment of a potential candidate.

PMID- 15571304
TI  - [CME-ultrasonography 1/Solution. Recurrent hypogastric pain].

PMID- 15571305
TI  - ["A destruction of reason" -- madness in medical theories of the 17th century].

PMID- 15571306
TI  - [Assessment of acoustic rhinometry in examining nasal ventilation function].
AB  - OBJECTIVE: To evaluate the use of acoustic rhinometry (AR) in determination of
      nasal ventilation function in patients complaining of nasal obstruction, and to
      discuss the selection of parameters. METHOD: Acoustic rhinometry was measured in
      36 patients complaining of nasal obstruction with nasal diseases and 20 adults
      without nasal obstruction as control, the parameters including mean nasal cross
      sectional area (MNCA), minimal cross-sectional area (MCA), volume of nasal cavity
      (NV) and nasal resistance (NR). RESULT: There is no sex difference for MNCA, MCA,
      NV and NR measured in control group (P > 0.05), and no lateral difference except
      NV (P < 0.05). MCA and NR show remarkable difference between patients and control
      (P < 0.05). CONCLUSION: Acoustic rhinometry can be adopted as an objective way to
      evaluate the nasal ventilation. Since MCA and NR coincide with the subjective
      perception of patients, they can be used as the sensitive parameters to evaluate
      the nasal ventilation function.

PMID- 15571307
TI  - [Study on the polymorphism of angiotensin converting enzyme genes and serum
      angiotensin II level in patients with obstructive sleep apnea hypopnea syndrome
      accompanied hypertension].
AB  - OBJECTIVE: To explore the relationship of the ACE gene insertion/deletion (I/D)
      polymorphism and the rennin-angiotensin system in the pathogenesis of
      hypertension in OSAHS. METHOD: Gene DNA was extracted from blood samples and
      amplified by polymerase chain reaction (PCR). The distribution of.the ACE gene
      I/D allele and genotypes were analyzed in 30 OSAHS with hypertension patients, 30
      normotensive OSAHS patients and 30 healthy control group without cardiovascular
      diseases. The serum level of angiotensin II were also measured in all subjects by
      angiotensin II enzyme immunoassay kit. RESULT: The frequency of II genotype and I
      allele were significantly higher in the OSAHS accompanied hypertension patients
      than those in the healthy controls (chi2=9.88, chi2=16.13, P<0.01, respectively)
      and in the normotensive OSAHS patients (chi2=5.67, P<0.05, chi2=8.61, P<0.01).
      The frequency of II genotype and I allele had no significantly different between
      the normotensive OSAHS patients and the healthy controls (P>0.05). The serum
      level of angiotensin II was significantly higher in both OSAHS patients with and
      without hypertension than that in the healthy control (t=3.66, t=3.23,
      respectively P<0.01). Whereas the serum level of angiotensin II have no
      significantly different in the OSAHS patients with and without hypertension
      (P>0.05). CONCLUSION: These results indicate that the higher frequency of ACE
      gene I allele and genotype are closely associated with OSAHS patients accompanied
      hypertension. It is one of the important risk factors for the genesis of
      hypertension in OSAHS. The activity of rennin-angiotension system is higher in
      the OSAHS may have contribute to OSAHS-induced hypertension.

PMID- 15571308
TI  - [The relationship between tumor angiogenesis and cellular proliferation activity
      in nasal inverted papilloma].
AB  - OBJECTIVE: To investigate the expression of CD34 and proliferating cell nuclear
      antigen (PCNA) and to study the relationship between tumor angiogenesis and
      cellular proliferation activity in nasal inverted papilloma (NIP). METHOD: The
      expression of CD34 protein and proliferating cell nuclear antigen were detected
      in 30 cases of NIP, 16 cases of nasal polyps (NP) and 11 cases of nasal squamous
      cell carcinoma (NSCC) with immunohistochemical S-P method and the tumor
      angiogenesis (as assessed by MVD) and cellular proliferation activity (as
      assessed by PCNA labeling index, PCNA-LI) was evaluated. RESULT: A significant
      difference in CD34 expression was found among the three diseases above mentioned.
      The MVD were 32.41 +/- 5.68; 53.22 +/- 9.31 and 80.37 +/- 10.21 in NP, NIP and
      NSCC. The expression rate of PCNA (PCNA-LI) was 28.67 +/- 9.29; 35.35 +/- 7.02
      and 63.18 +/- 12.17 in NP, NIP and NSCC (P<0.01). There was a significant
      difference in PCNA expression among the three diseases (P<0.01). A significant
      positive correlation was found between MVD and PCNA-LI (r=0.56, P<0.01). Tumors
      with a low PCNA-LI was associated with low MVD and vice versa. CONCLUSION: With a
      significant relation between tumor angiogenesis, cellular proliferation activity
      and pathological types, MVD, PCNA-LI can be used as a strong independent
      indicator to judge tumor aggressive behavior, proliferative activity, development
      of local or regional metastases and prognosis in nasal inverted papilloma.

PMID- 15571309
TI  - [Resection of giant pituitary adenomas through transnasal and transsphenoidal
      approach with nasoendoscope].
AB  - OBJECTIVE: To investigate the feasibility of transnasal and transsphenoidal
      surgery for giant pituitary adenomas with nasoendoscope. METHOD: The giant
      pituitary adenomas were resected by the transnasal and transsphenoidal surgery
      with nasoendoscope in 13 patients. RESULT: The tumors were totally resected in 9
      cases (69.2%), subtotally in 3 cases (23.1%) and the resection failed in 1
      (7.7%). Vision and visual field were significantly improved in 10 patients
      (76.9%) one week after the operations, of whom 7 had nearly or completely normal
      vision and visual field. There were no serious complications or death except
      transient cerebro spinal fluid leakage in 2 patients. CONCLUSION: It should be
      noted that the operative manipulation and curative effect of nasoendoscopic
      surgery on the giant pituitary adenomas may be affected by some factors such as
      the hemorrhage during the operation, anatomical abnormality, parasellar tissue
      projecting into the sella, postoperative improper treatment and so on.

PMID- 15571310
TI  - [Maxillary sinus polyp and cyst excised by endoscopes surgery in chronic
      sinusitis and significance].
AB  - OBJECTIVE: To look for a simple and convenient surgical method to treat the
      maxillary sinus polyp and cyst. METHOD: By means of Rudolf 4.5 mm cannula
      paracentetic needle trough inferior nasal meatus the polyp and cyst were be cut
      by cutter. RESULT: For half a year, 50 cases were followed and no relapse was
      found by X-ray or CT. CONCLUSION: Maxillary sinus polyp and cyst can be excised
      by endoscope surgery through inferior canal, and it is a minimally invasive
      operation. The effective is positive.

PMID- 15571311
TI  - [To repair perforation of nasal septum with free mucosa of inferior turbinate].
AB  - OBJECTIVE: To study a new treatment to repair perforation of nasal septum with
      free mucosa of inferior turbinate between two sides of mucosa of nasal septum.
      METHOD: The mucosa around perforation of nasal septum was separated by means of
      submucous correction of nasal septum, and some mucosa of inferior turbinate was
      cut down, then the mucosa bag of nasal septum and the free mucosa of inferior
      turbinate were sutured and the perforation could be covered completely. RESULT:
      The perforations of nasal septums in 21 patients were closed satisfactorily.
      Perforation of nasal septum did not recur and the follow-up time ranged from 3
      months to half a year. CONCLUSION: The free mucosa of inferior turbinate is easy
      to be got and survive. What's more, it can be used to repair a big perforation of
      nasal septum. Our method is easy to be performed and the free mucosa can be fixed
      tightly.

PMID- 15571312
TI  - [Expression and correlation with metastasis of E-cadherin, CD44H, matrix
      metalloproteinase-3, nm23H1 and VEGF in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the expression of E-cadherin, CD44H, matrix
      metalloproteinase-3, nm23H1 and VEGF in nasopharyngeal carcinoma and its
      relationship to the metastasis. METHOD: The expression of E-cadherin, CD44H,
      matrix metalloproteinase-3, nm23H1 and VEGF in 62 patients with nasopharyngeal
      carcinoma was detected by immunohistochemical SP method. RESULT: In the group of
      nasopharyngeal carcinoma with lymph node metastasis, the expression of E-cadherin
      and nm23H1 reduced and the expression of CD44H and MMP-3 increased, and there
      were respectively significant difference compared to the group of non-lymph node
      metastasis, but there wasn't significant difference between the two groups in
      VEGF. Furthermore, expression of E-cadherin was inversely correlated with that of
      CD44H and MMP-3, and the expression of CD44H was positively correlated with that
      of MMP-3. In the group of nasopharyngeal carcinoma with distant metastasis, the
      expression of E-cadherin and nm23H1 also increased and the expression of CD44H,
      MMP-3 and VEGF all increased. Compared with the group of negative distant
      metastasis, there were respectively significant difference. In addition, there
      was a positive correlation between the expression of CD44H and VEGF. CONCLUSION:
      E-cadherin, CD44H, matrix metalloproteinase-3 and nm23H1 genes are closely
      related with lymph node and distant metastasis of nasopharyngeal carcinoma, while
      VEGF gene only relates to lymph node metastasis. They are important factors
      acting on metastasis of neoplasms.

PMID- 15571313
TI  - [Endoscopic extralaryngeal approach subtotal arytenoidectomy in the treatment of
      bilateral vocal cord paralysis].
AB  - OBJECTIVE: To evaluate endoscopic extralaryngeal approach subtotal
      arytenoidectomy for the treatment of bilateral vocal cord paralysis. METHOD:
      Thirteen cases of bilateral median vocal cord paralysis was operated by
      endoscopic extralaryngeal approach unilateral subtotal arytenoidectomy. All of
      them had tracheostomy before. The airway was modified about 5-6 mm via endoscopic
      in operating. The airway was evaluated by fibro laryngoscopy, and the voice
      quality was assessed subjectively by the patients and the surgeon before and
      after surgery. RESULT: All cases were followed-up 6-36 months. The function of
      airway successfully restored, and the voice quality was kept satisfactory. All
      patients were decannulated after 8 to 15 days within the mean time 11.5 days post
      operation. There were no granulation and no aspiration at the surgical site post
      operateally. CONCLUSION: The operation of extralaryngeal approach unilateral
      subtotal arytenoidectomy in endoscopy is a better restoration of airway with
      satisfying voice and without aspiration after operation. The procedure is simple,
      reliable and efficient for treatment of patients with bilateral median vocal cord
      paralysis.

PMID- 15571314
TI  - [Slow-release transdermal fentanyl used as anesthesia aided drug in ESS
      operation].
AB  - OBJECTIVE: To observe the safety of slow-release transdermal fentanyl (TDF) used
      as anesthesia aided drug in endoscopic sinus surgery (ESS) peri-operation.
      METHOD: In 30 cases of ESS operation, we observed their blood pressure, pulse and
      degree of blood oxygen saturation (SpO2%) before the TDF patch used and 10 min,
      20 min, 30 min, 60 min after the patch used, their results were compared in
      respective. We observed the morbidity rate of patients accompanied with nausea,
      vomiting, bad appetite, skin reaction and vertigo at the same time. RESULT: There
      were no significant difference of blood pressure before and after the patch used,
      and so were the pulse and SpO2%. There were no patients accompanied with
      vomiting, vertigo and skin reaction. Four cases accompanied with nausea and bad
      appetite. CONCLUSION: TDF is a safe, effective and convenient anesthesia aided
      drug in ESS peri-operation.

PMID- 15571315
TI  - [Follow-up surveying the clinical effects after the endoscopic sinus surgery].
AB  - OBJECTIVE: To explore the follow-up time and the effect of intranasal
      glucocorticoid for chronic sinusitis and nasal polyps after endoscopic sinus
      surgery. METHOD: After the endoscopic sinus surgery, 30 cases of sinusitis and
      nasal polyps accepted the postsurgical care for the cavity, sinus washing, and
      intranasal local glucocorticoid rhinocort, then the clinical effects was follow
      up surveyed. RESULT: Intranasal local glucocorticoid could evidently reduce the
      courses of dry and the epithelial metaplasia of nasal cavity and sinus.
      CONCLUSION: After the endoscopic sinus surgery, follow-up of endoscopic sinus,
      postsurgical care for the cavity and intranasal local glucocorticoid played
      equally important roles in treating sinusitis and nasal polyps.

PMID- 15571316
TI  - [Clinical examination of mizolastine in the seasonal allergic rhinitis].
AB  - OBJECTIVE: An open randomized comparative study versus loratadine was conducted
      in order to examine the efficacy and safety of mizolastine in the treatment of
      seasonal allergic rhinitis (SAR). METHOD: Six-seven adult patients completed
      mizolastine 10 mg (34/67) and loratadine 10 mg (33/67) once daily for 14 days.
      Other 5 patients withdrew or dropped out from the trial. RESULT: All symptom
      score decreased significantly after treatment in both groups. Efficacy assessment
      based on symptom score reducing index showed that the efficacy of Mizolastine was
      82.4%, and the excellent rate was 20.6%, while the efficacy of Loratadine was
      66.7%, and the excellent rate was 6.1%. No serious adverse events were reported
      in the two groups. The incidences of adverse drug reactions (ADRs) of Mizolastine
      and Loratadine were 38.2% and 33.3% respectively. The mild or moderate drowsiness
      and dry mouth in Mizolastine group were 26.5% and 8.8% respectively, and in
      Loratadine group they were 18.2% and 9.0%. There were no significant changes in
      laboratory examinations including blood and urine routine tests, liver and renal
      functions and ECG. CONCLUSION: Mizolastine is effective in relieving SAR
      symptoms. The efficacy and ADR of mizolastine is similar to Loratadine in the
      treatment of SAR.

PMID- 15571317
TI  - [The feathers of Wegener granulomatosis in otorhinolaryngology].
AB  - OBJECTIVE: In order to study the characteristic of Wegener granulomatosis in
      otorhinolaryngology. METHOD: We investigated and treated 6 patients. RESULT: Five
      cases were remission, 1 case died. CONCLUSION: The feathers of Wegener
      granulomatosis in otorhinolaryngology have nothing in common with each other, the
      characteristic of clinic is complicate, cyclophosphamide deltasone and co
      trimoxazole are effective.

PMID- 15571318
TI  - [The study of producing allogenic-tissue engineering cartilage].
AB  - OBJECTIVE: To explore the feasibility of producing neocartilage tissue by using
      allogenic chondrocytes as seeding cells, artificial absorbable scaffold
      polylactic acid (PLA) as matrices. METHOD: The cartilage tissue was obtained from
      the four limbs of neoborn New Zealand rabbits (born 3-5 days), digested by II
      collagenase, proliferated in vitro, then seeded the chondrocytes on PLA
      scaffolds. The chondrocyte-PLA complex were cultured 7-10 days in vitro, then
      implanted in dorsal subcutaneous of adult New Zealand rabbits. Specimens
      harvested 3 weeks, 5 weeks and 7 weeks after implantation respectively and
      subjected to histologic analysis. RESULT: Chondrocyte-PLA complex implanted in
      adult new Zealand rabbits for 7 weeks, produced neo-cartilage as proved by
      histologic analysis, along with time extending, chondrocyte matrice secretion
      increased, invading inflammatory cell decreased. CONCLUSION: Using allogenic
      chondrocytes as seeding cells and PLA scaffold, it is successful to generate
      allogenic tissue-engineering cartilage in animals that have inherent immunity.

PMID- 15571319
TI  - [Morphologic study of nasolacrimal duct mucosa-associated lymphoid tissue].
AB  - OBJECTIVE: To investigate the features of nasolacrimal duct MALT (mucosa
      associated lymphoid tissue), and to explore the aetiology of chronic
      dacryocystitis. METHOD: The mucous of nasolacrimal duct, nasal cavity, pharyngeal
      and trachea of 20 rabbits were studied, and the lymphoid tissue and HEV of them
      were compared. RESULT: The number of lymphoid follicle and HEV in nasolacrimal
      duct epidermis were less than that in nasal cavity, pharyngeal and trachea
      (P<0.01). CONCLUSION: In normal condition the immune response of nasolacrimal
      duct membranae is lower than other mucosa of head-neck.

PMID- 15571320
TI  - [Innovation and practice of college educational system in otorhinolaryngology].
AB  - OBJECTIVE: A series of educational innovation was performed in order to resolve
      the difficulties and conflict in the education of otorhinolaryngology of medical
      college. METHOD: The college educational system of otorhinolaryngology was
      established and put in practice in four grades of medical undergraduate students
      of 1997-2000 grade. RESULT: The scores and ability of medical students in
      otorhinolaryngology are improved significantly. Educational supervisors and the
      managers give high appreciation to the educational innovation of
      otorhinolaryngology. It was demonstrated that the innovated educational system is
      satisfactory for the college education of otorhinolaryngology. CONCLUSION: The
      innovated college educational system of otorhinolaryngology afford a good way to
      solve the difficulties and conflict in the college education of
      otorhinolaryngology. It is also valuable to other subjects in the clinical
      medical education of college education system.

PMID- 15571321
TI  - Electrochemical antigen-retrieval of formaldehyde fixed and paraffin-embedded
      archived leprosy skin biopsies.
AB  - While formaldehyde fixation preserves tissue morphology, it often hinders
      immunodetection of antigens in paraffin-embedded tissue because the antigens are
      masked. Antigen unmasking can be achieved with treatments such as microwave
      irradiation but they often lead to excessive tissue damage. Therefore, an
      electrochemical antigen-retrieval method (EAR) was devised in which an
      alternating electric current is passed through the tissue in a chamber containing
      an electrolyte buffer. The results obtained with this method were compared to
      those after microwave irradiation using archived samples of formaldehyde-fixed
      and paraffin-embedded lepromatous leprosy skin. The efficacy of the two unmasking
      procedures was assessed by the immunodetectability of several marker antigens
      using 24 antibodies. Fifteen antibodies that were directed against transmembrane
      proteins (CD), and the remaining 9 against cytokeratins 18.6 and 19, laminin,
      vimentin, S100a, BCG, Ulex europaeus lectin, PCNA, and P21ras. Simple and double
      immunohistochemistry was performed using the universal ENVISION and LSAB + AP
      detection systems. After unmasking with the EAR method, immunoreactivity was
      clearly detected with 22 of the 24 antibodies in single labeling reactions. They
      include the critical antigens CD3 and CD4 for identifying the T lymphocyte
      lineages. In contrast, only 20 of the antibodies reacted after microwave
      irradiation. After double immunolabeling, immunoreactivity was quantitatively
      similar with both methods. However, the EAR unmasking produced a stronger
      labeling reaction. Thus, with double labeling immunohistochemistry, EAR made it
      possible to use higher antibody dilutions and shorter incubation times. Heat
      damage was also prevented. In conclusion, EAR treatment produces better staining
      results than microwave irradiation treatment.

PMID- 15571322
TI  - Cellular protein and mRNA expression patterns of matrix metalloproteinases-2, -3
      and -9 in human breast cancer: correlation with tumour growth.
AB  - The expression of matrix metalloproteinases (MMPs) with type IV collagenase
      activity has been associated with tumour invasion and metastatic potential in
      experimental models. We studied whether the cellular localization of MMP
      expression provides useful information on tumour behaviour in human breast
      cancer. Immunohistochemistry and non-radioisotopic-detected in situ hybridization
      were used to study protein and mRNA expression profiles for MMPs-2, -3 and -9 in
      paraffin sections of 70 invasive breast carcinomas. Protein and mRNA expression
      of the MMPs was observed in tumour as well as in peritumoural stromal cells. MMP
      protein expression was increased at the invasive border (p < 0.05). Grade 3
      carcinomas expressed MMP-2 mRNA in significantly more tumour cells than grade 2
      carcinomas (p = 0.006). Ductal carcinomas with an extensive intraductal component
      were characterized by the lowest percentages of MMPs-2 and -3 mRNA expressing
      peritumoural stromal cells (p < 0.05). No correlation was observed between MMP
      protein/mRNA expression and pTNM classification. In conclusion our results
      indicate that the expression of MMPs is associated with tumour behaviour. The
      correlation of MMPs-2 and -3 expression in peritumoural stromal cells with tumour
      type, shown for the first time, suggests that transcriptional regulation of these
      MMPs in stromal cells is important for the growth pattern of breast cancer.

PMID- 15571323
TI  - S-100 protein immunoreactivity in the upper eyelid of the sheep Ovis aries.
AB  - The aim of this work was to analyse the distribution pattern of S-100
      immunoreactive elements in the upper eyelid of the sheep. This pattern may be of
      importance regarding the diagnosis and prognosis of eyelid tumours that are
      linked to deregulation of S-100 gene expression. Thirty upper eyelids taken from
      15 adult male Ovis aries were studied by means of the peroxidase-antiperoxidase
      method for light microscopy. S-100-immunopositive cells were found in the eyelid
      edge. S-100-immunopositive steams and thinner fibres were found throughout the
      eyelid. These nerve processes typically were denser around glands, hair follicles
      and blood vessels. S-100-immunopositive elements may play a role as
      neuromodulator and also in the development of the vegetative innervation of the
      epithelium and its derivatives.

PMID- 15571324
TI  - Enhanced connexin-43 and alpha-sarcomeric actin expression in cultured heart
      myocytes exposed to triiodo-L-thyronine.
AB  - This study examined whether triiodo-L-thyronine (T3) affects the expression of
      the major intercellular channel protein, connexin-43, and contractile protein
      alpha-sarcomeric actin. Cultured cardiomyocytes from newborn rats were treated on
      day three in culture with 10 or 100 nM T3 and examined 48 and 72 h thereafter.
      Treated and untreated cells were examined by immunofluorescence and electron
      microscopy. Expression levels of Cx43 and sarcomeric alpha-actin were monitored
      by Western blot analysis. Immunofluorescence labeling showed cell membrane
      location of Cx43 in punctuate gap junctions, whereby fluorescence signal area was
      significantly higher in cultured cardiomyocytes exposed to T3. This correlated
      with electron microscopical findings showing increased numbers and size of gap
      junction profiles, as well as with a significant dose-dependent increase of Cx43
      expression detected by Western blot. Immunofluorescence of sarcomeric a-actin was
      enhanced and its expression increased dose- and time-dependently in T3-treated
      cultured heart myocytes. However, exposure to the higher dosage (100 nM) of T3
      caused mild disintegration of sarcomeric a-actin in some myocytes, suggesting an
      over-dosage. The results indicate that T3 up-regulates Cx43 and accelerates gap
      junction formation in cultured neonatal cardiomyocytes. They suggest that thyroid
      status cannot only modulate the mechanical function of cardiomyocytes but also
      cell-to-cell communication essential for myocardial electrical and metabolic
      synchronizations.

PMID- 15571325
TI  - Novel oxidative self-anchoring fluorescent substrates for the histochemical
      localization of endogenous and immunobound peroxidase activity.
AB  - Some 2-(2-styryl)-benzothiazole derivatives have been synthesized as novel
      fluorescent substrates for the localization of peroxidase activity. Excellent
      localization, high staining sensitivity and exceptionally low background staining
      were achieved by optimizing the choice of substrate. Multiple step-by-step
      anchoring of enzymatically-activated individual substrate molecules to
      surrounding nucleophiles, related to the catalysed reporter deposition (CARD)
      technique, is discussed. In contrast to tyramine conjugates, as employed in the
      CARD technique, the separation between reporting and anchoring function is
      eliminated, thus yielding a new fluorochrome with altered fluorescence properties
      after enzymatic cross-linking. (E)-2-(2-[4-hydroxyphenyl] vinyl)-3-ethyl-1,3
      benzothiazolium iodide has been found to the best substrate so far. This was
      demonstrated in histochemical applications for the localization of endogenous and
      immunobound peroxidase activity using fixed cryostat, paraffin or semi-thin Epon
      sections. The specific final reaction product is efficiently excitable over a
      wide spectrum from green to violet, providing an outstanding sensitive
      localization of sites of enzymatic activity with high photo stability. In a
      comparative study with the Alexa Fluor 546-tyramine conjugate, endogenous and
      immunobound peroxidase activity was visualized and the results compared using an
      epi-fluorescence confocal laser scanning microscope. The novel substrate provided
      an improved specificity and very low background staining whereas the Alexa Fluor
      tyramide exhibited a strong overall background staining. FITC-labelled secondary
      antibodies also yielded very low background staining but the staining was less
      specific compared with the biotin-based ABC amplification systems labelled with
      the selected substrate or the Alexa-tyramide. In conclusion, multiple
      fluorochrome generation close to sites of peroxidase activity, by enzymatic cross
      linking of styrene-related substrates, is a promising alternative to the
      fluorochrome-labelled tyramine ('tyramide') deposition technique.

PMID- 15571326
TI  - Early onset of lipofuscin accumulation in dystrophin-deficient skeletal muscles
      of DMD patients and mdx mice.
AB  - Lipofuscin, the so-called ageing pigment, is formed by the oxidative degradation
      of cellular macromolecules by oxygen-derived free radicals and redox-active metal
      ions. Usually it accumulates in post-mitotic, long-lived cells such as neurons
      and cardiac muscle cells. In contrast, it is rarely seen in either normal or
      diseased skeletal muscle fibres. In this paper, we report that lipofuscin
      accumulates at an early age in both human and murine dystrophic muscles.
      Autofluorescent lipofuscin granules were localized, using confocal laser scanning
      microscopy and electron microscopy, in dystrophin-deficient skeletal muscles of X
      chromosome-linked young Duchenne muscular dystrophy (DMD) patients and of mdx
      mice at various ages after birth. Age-matched normal controls were studied
      similarly. Autofluorescent lipofuscin granules were observed in dystrophic biceps
      brachii muscles of 2-7-year-old DMD patients where degeneration and regeneration
      of myofibres are active, but they were rarely seen in age-matched normal
      controls. In normal mice, lipofuscin first appears in diaphragm muscles nearly 20
      weeks after birth but in mdx muscles it occurs much earlier, 4 weeks after birth,
      when the primary degeneration of dystrophin-deficient myofibres is at a peak.
      Lipofuscin accumulation increases with age in both mdx and normal controls and is
      always higher in dystrophic muscles than in age-matched normal controls. At the
      electron microscopical level, it was confirmed that the localisation of
      autofluorescent granules observed by light microscopy in dystrophin-deficient
      skeletal muscles coincided with lipofuscin granules in myofibres and myosatellite
      cells, and in macrophages accumulating around myofibres and in interstitial
      connective tissue. Our results agree with previous biochemical and histochemical
      data implying increased oxidative damages in DMD and mdx muscles. They indicate
      that dystrophin-deficient myofibres are either more susceptible to oxidative
      stress, or are subjected to higher intra- or extracellular oxidative stress than
      normal controls, or both.

PMID- 15571327
TI  - Cytochemical and histochemical aspects of the digestive gland cells of the mussel
      Mytilus galloprovincialis (L.) in relation to function.
AB  - The epithelium of the digestive tubules of the mussel Mytilus galloprovincialis
      is comprised of two cell types, namely digestive and basophilic cells. In
      basophilic cells, the secretory granules are beta-glucuronidase immunoreactive, a
      fact that enhances the hypothesis that beta-glucuronidase is synthesized in
      basophilic cells. A novel observation at the ultrastructural level is the
      pinocytic activity associated with the formation of coated pits. This observation
      constitutes direct evidence for endocytic processes taking place in basophilic
      cells. The use of cryostat sections from the same digestive tubules reveals, in
      many instances, a very pronounced neutral lipid accumulation in the same
      structures giving a positive reaction for N-acetyl-beta-hexosaminidase,
      indicating the association of those lipids with lysosomes. In some mussels, a
      high content of lipofuscin was observed in the lysosomes of the digestive cells.
      In these cases, the lysosomal structures show a limited neutral lipid content,
      and a weaker N-acetyl-beta-hexosaminidase reaction. In the digestive cells, the
      carbohydrate content of the lysosomes, and very well-developed canal system in
      the apical part of cells are discussed in relation to their function.

PMID- 15571328
TI  - Immunohistochemical demonstration of leptin in pancreatic islets of non-obese
      diabetic and CD-1 mice: co-localization in glucagon cells and its attenuation at
      the onset of diabetes.
AB  - Leptin is a 16 kD polypeptide hormone produced predominantly by white adipose
      tissue and exerts profound effects on food intake and energy balance. More recent
      studies have shown extra sites of leptin production in human and rodent tissues
      and have ascribed additional roles for the hormone, e.g., in immune and
      reproductive functions. A role for the hormone has also been implicated in
      insulin-dependent diabetes mellitus in the non-obese diabetic (NOD) mouse.
      However, whether leptin originates from islet cells of the mouse is not known.
      Here dual-label immunohistochemistry was employed to examine leptin expression in
      islet cells, and its distribution and cellular sources in pancreatic sections of
      female NOD/Ak and CD-1 mice of various ages. For comparison, leptin
      immunolabelling was examined in adult pancreatic sections from male NOD/Ak CD-1,
      Balb/c and FVB/N mice and female severe combined immunodeficient CB. 17 mice.
      Pancreatic tissues from adult female guinea pig, sheep and cattle and neonatal
      pigs were also studied. Our results show that in the day 1 NOD and CD-1 mice,
      leptin immunolabelling was observed in selective glucagon cells within the
      developing islets while at days 15 and 22, it became more intense and co
      incident. This pattern of staining was maintained at days 40, 90, 150 and 250. In
      the female NOD mouse, leptin was absent in intra-islet immune cells. Its
      expression was variable in islets from male NOD and CD-1 mice. In spontaneously
      diabetic female NOD mice and following acceleration of diabetes with
      cyclophosphamide, despite the persistence of strong immunolabelling for glucagon
      in the re-distributed alpha cells, leptin expression was either absent,
      diminished or present in only a proportion of alpha cells. The reduction in
      leptin labelling was often associated with diabetic islets which had insulitis in
      association with only a small number of residual beta cells. Leptin expression
      was absent in guinea pig, ovine, bovine and neonatal porcine islet cells, despite
      the expression of intensely labelled glucagon cells. The present results
      demonstrate leptin co-localization in glucagon cells of the mouse islet. Its
      expression diminishes in the presence of inadequate insulin. Leptin produced
      within the mouse islet may have bi-directional influences on leptin and insulin
      regulation and may play local functions in islet development and metabolism.

PMID- 15571329
TI  - Distribution of apelin, the endogenous ligand of the APJ receptor, in the lizard
      Podarcis sicula.
AB  - Apelin is a novel bioactive peptide that has been isolated from bovine stomach
      extracts and identified as the endogenous ligand for the APJ receptor. Although
      the main physiological functions of apelin have not yet been clarified, it is
      known that apelin is involved in the regulation of blood pressure, central
      control of body fluid homeostasis and the modulation of immune response. In order
      to investigate the distribution of apelin in reptiles, we have performed an
      immunohistochemical analysis on tissues of the lizard Podarcis sicula. The
      peptide was found to be widely distributed, although its cellular localization
      differed in the various organs examined. A strong immunopositivity was found in
      the heart, stomach and intestine. In the spleen, an intense apelin
      immunopositivity was restricted to a discrete number of cells scattered
      throughout the red pulp and co-localized with immunoglobulin kappa and lambda
      chains, suggesting an analogous function of this peptide in immune responses also
      in reptiles. Intriguingly, apelin immunoreactivity was discretely localized in
      endothelial cells in the lung and thyroid gland. In the light of these data, we
      conclude that apelin may have multiple functions in reptiles.

PMID- 15571330
TI  - Immunogold localization of tight junctional proteins in normal and osmotically
      affected rat blood-brain barrier.
AB  - The distribution of molecular components of interendothelial tight junctions
      (TJs) was studied in rat blood-brain barrier (BBB) microvessels, using immunogold
      cytochemistry applied to electron microscopy. Samples of rat brains, both normal
      (unaffected) and osmotically-affected (1, 5, and 30 min after intracarotid
      infusion of 1.8 M L(+)arabinose), were processed for immunocytochemical
      localization of TJ-specific integral membrane (occludin, JAM-1, claudin-5) and
      peripheral (ZO-1) protein molecules. In unaffected interendothelial junctions of
      control rats the immunosignals (represented by gold particles) for occludin and
      ZO-1 were of highest, whereas for claudin-5 and JAM-1 were of lower density. At 1
      min after infusion, no discernible changes in distribution of junction-associated
      molecules were noted. At 5 min, however, changes were most conspicuous, and they
      consisted of segmental attenuation of the endothelial lining and dilatation
      (opening) of some junctional clefts accompanied by the diminution of the density
      of immunosignals for TJ-specific transmembrane and peripheral proteins. It was
      paralleled by disorganization of the spatial relation of these molecules to the
      junctional complexes. After 30 min, many interendothelial junctions appeared to
      be still open, whereas other junctions were partially or totally closed. In the
      opened interendothelial junctions the expression of TJ-associated molecules was
      weaker than in closed junctions. Our observations indicate that the localization
      and expression of TJ-specific proteins, especially occludin, and in lower degree
      claudin-5 and JAM-1, together with the peripheral ZO-1 molecules, are affected by
      osmotic shock. Presumably, some of these proteins (e.g., occludin, claudin-5 and
      ZO-1) could be considered sensitive indicators of normal and also of disturbed
      functional state of the BBB.

PMID- 15571331
TI  - Stable-isotope trapping and high-throughput screenings of reactive metabolites
      using the isotope MS signature.
AB  - A highly efficient method has been developed to detect and identify reactive
      metabolites, using stable-isotope trapping combined with ESI-MS/MS neutral loss
      scanning. A mixture of glutathione (GSH, gamma-glutamylcysteinylglycine) and the
      stable-isotope labeled compound (GSX, gamma-glutamylcysteinylglycine-(13)C(2)
      (15)N) was used at an equal molar ratio to trap reactive metabolites generated in
      microsomal incubations. Samples resulting from incubations were cleaned and
      concentrated by SPE, followed by LC-MS/MS analyses using constant neutral loss
      scanning for 129 Da (the gamma-glutamyl moiety) to detect formed GSH conjugates.
      Unambiguous identification of glutathione adducts was greatly facilitated by the
      presence of a unique MS signature of a prominent isotopic doublet that differs in
      mass by 3 Da. Further structural characterization of conjugates was achieved with
      high confidence by subsequently acquiring MS/MS spectra that were featured by
      neutral losses of 75 and 129 Da for GSH adducts and 78 and 129 Da for isotopic
      GSX adducts. The reliability of this method was vigorously validated using a
      number of compounds known to form reactive metabolites. Superior sensitivity was
      demonstrated by the capability of the current approach to identify reactive
      metabolites at low abundance. Because of the unique isotopic MS signature,
      ultrafast analyses of reactive metabolites were accomplished by direct injection
      of cleaned samples into mass spectrometers for neutral loss scanning. More
      importantly, this study has demonstrated the feasibility of the current method
      for completely automated detection of reactive metabolites via computer-assisted
      pattern recognition.

PMID- 15571332
TI  - Use of performic acid oxidation to expand the mass distribution of tryptic
      peptides.
AB  - Significant identification of proteins by mass fingerprinting and partial
      sequencing of tryptic peptides is central to proteomics. However, peptide masses
      cluster with distances of approximately 1 Da. Expanding these clusters will give
      more peptides of unique masses, thereby identifying proteins with a higher
      significance. The mass clusters can be expanded downward by including more oxygen
      atoms in the peptides. Classic performic acid oxidation modifies three residues,
      Cys to CysO(3), Met to MetO(2), and Trp to TrpO(2). In this study, we compare the
      mass distributions of tryptic peptides computed from the predicted proteomes of
      Bacillus subtilis, Drosophila melanogaster, Arabidopsis thaliana, and Homo
      sapiens modified by oxidation, reduction, and reduction followed by
      carboxymethylation, carboxamidomethylation, or pyridylethylation. Forty to 46% of
      the eukaryotic tryptic peptides contain Cys, Met, or Trp. Additionally, the
      importance of mass accuracy of differentially modified tryptic peptides for
      significant protein identification by database searches was analyzed. The results
      show that performic acid oxidation gives markedly extended mass distributions at
      mass accuracies from +/-0.002 to +/-0.25 Da for the eukaryotes. The effect of the
      expanded mass distribution on significant protein identification was illustrated
      by searching simulated mass peak lists against the databases containing oxidized
      and reduced tryptic peptides. The specificity of formic acid oxidation was tested
      experimentally, and no general adverse effects were detected. Tryptic peptides
      provided a 100% sequence coverage of oxidized barley grain peroxidase by LC-MS,
      and the sequence coverages of oxidized and carboxymethylated bovine serum albumin
      were similar by MALDI-TOF MS analyses.

PMID- 15571333
TI  - Statistical model for large-scale peptide identification in databases from tandem
      mass spectra using SEQUEST.
AB  - Recent technological advances have made multidimensional peptide separation
      techniques coupled with tandem mass spectrometry the method of choice for high
      throughput identification of proteins. Due to these advances, the development of
      software tools for large-scale, fully automated, unambiguous peptide
      identification is highly necessary. In this work, we have used as a model the
      nuclear proteome from Jurkat cells and present a processing algorithm that allows
      accurate predictions of random matching distributions, based on the two SEQUEST
      scores Xcorr and DeltaCn. Our method permits a very simple and precise
      calculation of the probabilities associated with individual peptide assignments,
      as well as of the false discovery rate among the peptides identified in any
      experiment. A further mathematical analysis demonstrates that the score
      distributions are highly dependent on database size and precursor mass window and
      suggests that the probability associated with SEQUEST scores depends on the
      number of candidate peptide sequences available for the search. Our results
      highlight the importance of adjusting the filtering criteria to discriminate
      between correct and incorrect peptide sequences according to the circumstances of
      each particular experiment.

PMID- 15571334
TI  - Surface plasmon resonance: theoretical evolutionary design optimization for a
      model analyte sensitive absorbing-layer system.
AB  - Surface plasmon resonance (SPR) has been widely used in a Kretschmann
      configuration to study optical thickness changes of layers on a Au surface in
      response to an analyte. The method has been popularized and optimized for protein
      layers, but has also been used in the same format for other layers without
      further optimization including those absorbing at the incident wavelength. In
      this paper, we examine whether SPR remains the "best"attenuated reflectivity
      format for absorbing overlayers. Experimental data from the SPR response of a
      copper phthalocyanine film to nitrogen dioxide are used as an input example for a
      design process using an evolutionary algorithm. The data showed a trend toward
      thinner gold layer systems ( approximately 25 nm gave an contrast-enhancement of
      42.9% compared with approximately 50-nm Au) or Au-free solutions including a
      layer with low refractive index. From the evolutionary design predictions,
      further modification could be tested based on available materials and "redundant
      layers" could be eliminated from the final selection. By inclusion of the
      external optics, a design could be selected to accommodate poor precision (+/-0.5
      degrees ) in the incident angle and a possible multilayer solution was shown
      using Teflon AF 1600, with refractive index approximately 1.3. The predicted
      NO(2) response showed an improvement compared with the classical SPR
      configuration, and the incident angle chosen by the SGA for the interrogation of
      these layers was close to a stationary point in the absolute response curve, thus
      offering very good tolerance to automatic position referencing to the
      reflectivity minimum.

PMID- 15571335
TI  - Electrogenerated chemiluminescence from a CdSe nanocrystal film and its sensing
      application in aqueous solution.
AB  - Electrogenerated chemiluminescence (ECL) of semiconductor quantum dots in aqueous
      solutions and its first sensing application were studied by depositing CdSe
      nanocrystals (NCs) on a paraffin-impregnated graphite electrode (PIGE). The CdSe
      nanocrystal thin film exhibited two ECL peaks at -1.20 (ECL-1) and -1.50 V (ECL
      2) in pH 9.3, 0.1 M PBS during the cyclic sweep between 0 and -1.8 V at 20 mV s(
      1). The electron-transfer reaction between individual electrochemically reduced
      nanocrystal species and oxidant coreactants such as H(2)O(2) and reduced
      dissolved oxygen led to ECL-1. When mass NCs packed densely in the film were
      reduced electrochemically, assembly of reduced nanocrystal species could react
      with coreactants to produce another ECL signal, ECL-2. ECL-1 showed higher
      sensitivity to the concentration of oxidant coreactants than ECL-2 and thus was
      used for ECL detection of coreactant, H(2)O(2). A linear response of ECL-1 to
      H(2)O(2) was observed in the concentration range of 2.5 x 10(-7)-6 x 10(-5) M
      with a detection limit of 1.0 x10(-7) M. The fabrication of 10 CdSe nanocrystal
      thin-film modified PIGEs displayed an acceptable reproducibility with a RSD of
      1.18% obtained at H(2)O(2) level of 10 microM.

PMID- 15571336
TI  - Facilitated protamine transfer at polarized water/1,2-dichloroethane interfaces
      studied by cyclic voltammetry and chronoamperometry at micropipet electrodes.
AB  - Cyclic voltammetry and chronoamperometry at micropipet electrodes were applied to
      study the phase transfer of polypeptide protamine facilitated by complexation
      with charged ionophore dinonylnaphthalenesulfonate (DNNS) at polarized water/1,2
      dichloroethane (DCE) interfaces, i.e., sDNNS(-) (DCE) + protamine(n+) (aq) right
      harpoon over left harpoon protamine-DNNS complex (DCE). Well-defined current
      responses based on the selective protamine transfer were obtained reproducibly
      even in the presence of 0.12 M NaCl. The selective and reproducible responses
      make this voltammetric/amperometric approach an attractive alternative to the
      traditional potentiometric counterpart based on mixed potential responses, for
      which both protamine and Na(+) need to be transferred simultaneously. Using both
      organic- and water-filled micropipet electrodes, the reaction mechanism was
      studied under different mass-transfer conditions controlled by diffusion of
      protamine, DNNS, and the complex in the outer solution of the pipets. Both charge
      number of transferred protamine, n, and complexation stoichiometry, s, were
      determined to be approximately 20 by chronoamperometry. With these parameters,
      the electrochemically irreversible voltammograms were analyzed by assuming a one
      step transfer model to obtain experimental transfer coefficients, which represent
      apparent dependence of the transfer rate on the interfacial potential. The
      analysis showed that the transfer coefficients are much larger or smaller than a
      normal value of approximately 0.5 and strongly depend on the diffusion-limiting
      species, i.e., 0.088 +/- 0.005, 0.89 +/- 0.01, and 0.065 +/- 0.008 for protamine,
      DNNS, and the complex, respectively. The apparently anomalous transfer
      coefficients were explained consistently by a phenomenological model based on
      adsorption and transfer processes.

PMID- 15571337
TI  - Enzymatic genosensor on streptavidin-modified screen-printed carbon electrodes.
AB  - Voltammetric enzyme genosensors on streptavidin-modified screen-printed carbon
      electrodes (SPCEs) for the detection of virulence nucleic acid determinants of
      pneumolysin and autolysin genes, exclusively present on the genome of the human
      pathogen Streptococcus pneumoniae, were described. Alkaline phosphatase (AP) and
      3-indoxyl phosphate were used as the enzymatic label and substrate, respectively.
      The oligonucleotide probes were immobilized on electrochemically pretreated SPCEs
      through the streptavidin/biotin reaction. The adsorption of streptavidin was
      performed by deposition of a drop of a streptavidin solution overnight at 4
      degrees C on the surface of the SPCEs. After the hybridization reaction with FITC
      labeled complementary targets, the enzyme is captured using an anti-FITC antibody
      conjugated to AP. In nonstringent experimental conditions, these genosensors can
      detect 0.49 fmol of 20-mer oligonucleotide target and discriminate between a
      complementary oligo and an oligo with a three-base mismatch. In the presence of
      25% formamide in the hybridization buffer, a single-base mismatch on the
      oligonucleotide target can be detected.

PMID- 15571338
TI  - Scanning electrochemical microscopy, 52. Bipolar conductance technique at
      ultramicroelectrodes for resistance measurements.
AB  - The bipolar conductance, BICON, technique for the measurement of solution
      resistance, based on the application of microsecond current pulses, as originally
      described by Enke and co-workers for measurements with conventional electrodes,
      was extended for use with ultramicroelectrodes, with a focus on its application
      in scanning electrochemical microscopy (SECM). When the plateau time used to make
      the measurement lies within the BICON conditions, the solution conductance can be
      obtained directly from the output without the need for calibration curves.
      However, decreasing the size of the ultramicroelectrode decreases the range of
      values that satisfy these conditions, and one must resort to calibration curves
      to obtain solution conductance from the measured current, which was nevertheless
      found to be proportional to electrolyte concentration with electrodes as small as
      5 mum in diameter. BICON/SECM approach curves over insulating substrates followed
      SECM negative feedback theory and approach curves in the presence of low
      (micromolar) or no added electrolyte are possible once the background
      conductivity is taken into account. Approach curves to a conducting substrate at
      open circuit potential are influenced by the solution time constant (solution
      resistance at the electrode tip x electrode double layer capacitance), which is a
      function of the tip/substrate distance, as well as the substrate size.

PMID- 15571339
TI  - Electrochemical detection method for nonelectroactive and electroactive analytes
      in microchip electrophoresis.
AB  - In this work, we establish an indirect amperometric detection method via mounting
      a single carbon fiber disk working electrode in the end part of a microchannel.
      This in-channel configuration for microchip capillary electrophoresis brings
      about that the potential of the working electrode in the case of electrochemical
      reduction reaction is coupled by the separation electric field, while the
      potential of the working electrode in the case of electrochemical oxidation
      reaction is not coupled by the separation electric field. Such a special
      performance provides a convenient and sensitive approach for indirectly detecting
      nonelectroactive analytes that relies on amperometric response of dissolved
      oxygen in solution and directly detecting electroactive analytes based on their
      own amperometric response on the carbon fiber electrode. This method has shown
      its essential importance in the analysis of inorganic cations, biomolecules, and
      electroosmotic flow rates. Based on preliminary results, a detection limit of 1.0
      microM for K(+) and Na(+) have been achieved.

PMID- 15571340
TI  - Electrokinetic bioprocessor for concentrating cells and molecules.
AB  - Bioprocessors for concentrating bioparticles, such as cells and molecules, are
      commonly needed in bioanalysis systems. In this microfluidic processor, a global
      flow field generated by ac electroosmosis transports the embedded particles to
      the regions near the electrode surface. The processor then utilizes
      electrophoretic and dielectrophoretic forces, which are effective in short range,
      to trap the target cells and molecules on the electrode surface. By optimizing
      the operating parameters, we have concentrated various biological objects in a
      large range of sizes, including Escherichia coli bacteria, lambda phage DNA, and
      single-stranded DNA fragments as small as 20 bases that have a radius of gyration
      of only 3 nm.

PMID- 15571341
TI  - Quantatitive assessment of enzyme immobilization capacity in porous silicon.
AB  - Immobilized enzyme systems are important in a broad range of applications, from
      biological sensing to the industrial-scale biocatalytic synthesis of chiral
      products. We demonstrate the ability to systematically vary and quantitatively
      assess the immobilization capacity of porous silicon thin films for the enzyme
      glutathione-S-transferase in a manner predicted by a simple geometric model of
      the porous silicon matrix. We find that the immobilization capacity
      quantatitively correlates with systematic changes in the device thickness. These
      results are significant since, despite the wide range over which porous silicon
      morphology and surface area can be varied, few attempts have been made to
      systematically characterize surface binding capacity. Our findings suggest that
      porous silicon can be an ideal matrix, where immobilization of a predictable
      quantity of biological material is desired.

PMID- 15571342
TI  - Continuous monitoring of enzyme reactions on a microchip: application to
      catalytic RNA self-cleavage.
AB  - Kinetic analysis of RNA enzymes, or ribozymes, typically involves the tedious
      process of collecting and quenching reaction time points and then fractionating
      by polyacrylamide gel electrophoresis (PAGE). As a way to automate and simplify
      this process, continuous analysis of a ribozyme reaction is demonstrated here
      using completely automated capillary sample introduction onto a microfabricated
      device with laser-induced fluorescence detection. The method of injection is
      extremely reproducible thereby standardizing data analysis. A 30-nucleotide
      ribozyme model, the self-cleaving lead-dependent ribozyme, or "leadzyme", which
      cleaves into a 24-mer and a 6-mer in the presence of Pb(2+), was end-labeled with
      fluorescein (FAM) and used to demonstrate the potential of this technique. After
      manually initiating the cleavage reaction by Pb(2+) addition, reaction samples
      were automatically injected directly into the parallel separation lanes of the
      chip via a capillary at predetermined time intervals, thus eliminating the need
      for additional sample-handling steps. The FAM-labeled leadzyme starting material
      and products were monitored for 60 min in order to ascertain kinetic information.
      The effect of lead acetate concentration on cleavage rates was also studied, and
      the results are in agreement with rates determined by conventional hand
      mixing/PAGE analysis. This work demonstrates, through the use of a simple
      ribozyme model, the potential of this method to provide valuable kinetic
      information for other, more complex, biologically relevant RNA and protein
      enzymes.

PMID- 15571343
TI  - NIST mixed stain study 3: signal intensity balance in commercial short tandem
      repeat multiplexes.
AB  - Short-tandem repeat (STR) allelic intensities were collected from more than 60
      forensic laboratories for a suite of seven samples as part of the National
      Institute of Standards and Technology-coordinated 2001 Mixed Stain Study 3
      (MSS3). These interlaboratory challenge data illuminate the relative importance
      of intrinsic and user-determined factors affecting the locus-to-locus balance of
      signal intensities for currently used STR multiplexes. To varying degrees, seven
      of the eight commercially produced multiplexes used by MSS3 participants
      displayed very similar patterns of intensity differences among the different loci
      probed by the multiplexes for all samples, in the hands of multiple analysts,
      with a variety of supplies and instruments. These systematic differences reflect
      intrinsic properties of the individual multiplexes, not user-controllable
      measurement practices. To the extent that quality systems specify minimum and
      maximum absolute intensities for data acceptability and data interpretation
      schema require among-locus balance, these intrinsic intensity differences may
      decrease the utility of multiplex results and surely increase the cost of
      analysis.

PMID- 15571344
TI  - Pressurized electrochromatography coupled with electrospray ionization mass
      spectrometry for analysis of peptides and proteins.
AB  - Pressurized capillary electrochromatography (pCEC) was coupled with electrospray
      ionization mass spectrometry (ESI-MS) using a coaxial sheath liquid interface. It
      was used for separation and analysis of peptides and proteins. The effects of
      organic modifier and applied voltage on separation were investigated, and the
      effects of pH value of the mobile phase and the concentration of the electrolyte
      on ESI-MS signal were investigated. The resolution and detection sensitivity with
      different separation methods (pCEC, capillary high-performance liquid
      chromatography) coupled on-line with mass spectrometry were compared for the
      separation of a peptide mixture. To evaluate the feasibility and reliability of
      the experimental setup of the system, tryptic digests of cytochrome c and
      modified protein as real samples were analyzed by using pCEC-ESI-MS.

PMID- 15571345
TI  - Integrated lectin affinity microfluidic chip for glycoform separation.
AB  - Lectin affinity chromatography was miniaturized into a microfluidic format, which
      results in improvement of performance, as compared to the conventional method. A
      lectin affinity monolith column was prepared in the microchannel of a
      microfluidic chip. The porous monolith was fabricated by UV-initiated
      polymerization of ethylene dimethacrylate (EDMA) and glycidyl methacrylate (GMA)
      in the presence of porogeneities, followed by immobilization of pisum sativum
      agglutinin (PSA) on the monolith matrix. Using electroosmosis as the driven
      force, lectin affinity chromatographies of three kinds of glycoprotein, turkey
      ovalbumin (TO), chicken ovalbumin (CO), and ovomucoid (OM), were carried out on
      the microfluidic system. All the glycoproteins were successfully separated into
      several fractions with different affinities toward the immobilized PSA. The
      integrated system reduces the time required for the lectin affinity
      chromatography reaction to approximately 3%, thus, the overall analysis time from
      4 h to 400 s. Only 300 pg of glycoprotein is required for the whole separation
      process. Moreover, troublesome operations for lectin affinity chromatography are
      simplified.

PMID- 15571346
TI  - Surface-modified poly(methyl methacrylate) capillary electrophoresis microchips
      for protein and peptide analysis.
AB  - Polymeric materials have emerged as appealing alternatives to conventional
      inorganic substrates for the fabrication of microscale analytical systems;
      however, native polymeric surfaces typically require covalent modification to
      ensure optimum biocompatibility. 2-Bromoisobutyryl bromide was immobilized on
      poly(methyl methacrylate) (PMMA) substrates activated using an oxygen plasma.
      Atom-transfer radical polymerization was then performed to graft poly(ethylene
      glycol) (PEG) on the PMMA surface. PMMA microcapillary electrophoresis (muCE)
      devices made with the covalently modified surfaces exhibited substantially
      reduced electroosmotic flow and nonspecific adsorption of proteins on
      microchannel surfaces. Experiments using fluorescein isothiocyanate-conjugated
      bovine serum albumin indicated that both column efficiency and migration time
      reproducibility were 1 order of magnitude better with derivatized compared to
      untreated PMMA muCE chips. Fast, reproducible, and efficient separations of
      proteins and peptides were demonstrated using the PEG-grafted PMMA muCE chips.
      All analyses were completed in less than 60 s, and separation efficiencies as
      high as 5.2 x10(4) plates for a 3.5-cm-long separation channel were obtained.
      These results demonstrate the general applicability of surface-grafted PMMA
      microdevices for a broad range of protein analyses.

PMID- 15571347
TI  - Determination of enantiomeric excess in samples of chiral molecules using fourier
      transform vibrational circular dichroism spectroscopy: simulation of real-time
      reaction monitoring.
AB  - The first use of Fourier transform vibrational circular dichroism (FT-VCD) to
      follow changes in the percent enantiomeric excess (% EE) of chiral molecules in
      time using a flow cell sampling apparatus is reported. FT-VCD, as opposed to
      dispersive scanning VCD, eliminates the need to scan the VCD spectrum in time to
      monitor the % EE at more than one spectral location. The first use of partial
      least-squares chemometric analysis to determine % EE values from kinetic sets of
      VCD spectral data is also reported. These two advances have been used to monitor
      simultaneously changes in the fractional composition and the % EE of a mixture of
      two different chiral molecules. This simulates the progress of the chemical
      reaction from a chiral reactant to a chiral product where the % EE of both
      molecules can change with time. For the molecules studied, alpha-pinene, camphor,
      and borneol, the accuracy of following % EE changes for one species alone is
      approximately 1%, while for simultaneously following % EE changes in two species
      is approximately 2% for 10-20-min sampling periods at 4 cm(-)(1) spectral
      resolution. This accuracy can be increased for the same collection times or
      maintained for shorter periods of collection by lowering the spectral resolution.
      These findings demonstrate the potential for VCD to be used for real-time
      monitoring of the composition and % EE of chemical reactions involving the
      synthesis chiral molecules.

PMID- 15571348
TI  - DNA directed protein immobilization on mixed ssDNA/oligo(ethylene glycol) self
      assembled monolayers for sensitive biosensors.
AB  - A stable and versatile biosensor surface is prepared by site-directed
      immobilization of protein-DNA conjugates onto a mixed self-assembled monolayer
      (SAM) composed of ssDNA thiols and oligo(ethylene glycol) (OEG) terminated
      thiols. The protein conjugates consist of an antibody chemically linked to a
      ssDNA target with a sequence complementary to the surface-bound ssDNA probes and
      are immobilized on the surface via sequence-specific hybridization. Compared to
      standard antibody immobilization techniques, this approach offers many
      advantages. The exceptional specificity of DNA hybridization combined with the
      diversity of potential sequences makes this platform perfect for multichannel
      sensors. Once a surface is patterned with the appropriate probe sequences,
      sequence-specific hybridization will sort out the target conjugates and direct
      them to the appropriate spots on the surface. In addition, the DNA SAMs are very
      stable and well suited to recycling by dehybdridization of the conjugates from
      the surface-bound probes. In this work, we demonstrate the specificity,
      sensitivity, and convenience of using protein-DNA conjugates to convert a DNA/OEG
      SAM surface into a biosensor surface and apply this platform to the detection of
      human chorionic gonadotropin using surface plasmon resonance.

PMID- 15571349
TI  - Protein-protein interaction studies based on molecular aptamers by affinity
      capillary electrophoresis.
AB  - Protein-DNA/protein-protein interactions play critical roles in many biological
      processes. We report here the investigation of protein-protein interactions using
      molecular aptamers with affinity capillary electrophoresis (ACE). A human alpha
      thrombin binding aptamer was labeled with 6-carboxyfluorescein and exploited as a
      selective fluorescent probe for studying thrombin-protein interactions using
      capillary electrophoresis with laser-induced fluorescence. A 15-mer binding DNA
      aptamer can be separated into two peaks in CE that correspond to the linear
      aptamer (L-Apt) and the thrombin-binding G-quadruplex structure in the presence
      of K(+) or Ba(2+). In a bare capillary, the peak area of G-quadruplex aptamer (G
      Apt) was found to decrease with the addition of thrombin while that of L-Apt
      remained unchanged. Even though the peak of the G-Apt/thrombin binding complex is
      broad due to a weaker binding affinity between aptamer and thrombin, we were
      still able to quantify the thrombin and anti-thrombin proteins (human anti
      thrombin III, AT III) based on the peak areas of free G-Apt. The detection limits
      of thrombin and AT III were 9.8 and 2.1 nM, respectively. The aptamer-based
      competitive ACE assay has also been applied to quantify thrombin-anti-thrombin
      III interaction and to monitor this reaction in real time. The addition of
      poly(ethylene glycol) to the sample matrix stabilized the complex of the G
      Aptthrombin. This assay can be used to study the interactions between thrombin
      and proteins that do not disrupt G-Apt binding property at Exosit I site of the
      thrombin. Our aptamer-based ACE assay can be an effective approach for studying
      protein-protein interactions and for analyzing binding site and binding constant
      information in protein-protein and protein-DNA interaction studies.

PMID- 15571350
TI  - Identification of sites of ubiquitination in proteins: a fourier transform ion
      cyclotron resonance mass spectrometry approach.
AB  - Structural elucidation of posttranslationally modified peptides and proteins is
      of key importance in the understanding of an array of biological processes.
      Ubiquitination is a reversible modification that regulates many cellular
      functions. Consequences of ubiquitination depend on whether a single ubiquitin or
      polyubiquitin chain is added to the tagged protein. The lysine residue through
      which the polyubiquitin chain is formed is also critical for biological activity.
      Robust methods are therefore required to identify sites of ubiquitination
      modification, both in the target protein and in ubiquitin. Here, we demonstrate
      the suitability of Fourier transform ion cyclotron resonance (FT-ICR) mass
      spectrometry, in conjunction with activated ion electron capture dissociation (AI
      ECD) or infrared multiphoton dissociation (IRMPD), for the analysis of
      ubiquitinated proteins. Polyubiquitinated substrate protein GST-Ubc5 was
      generated in vitro. Tryptic digests of polyubiquitinated species contain modified
      peptides in which the ubiquitin C-terminal Gly-Gly residues are retained on the
      modified lysine residues. Direct infusion microelectrospray FT-ICR of the digest
      and comparison with an in silico digest enables identification of modified
      peptides and therefore sites of ubiquitination. Fifteen sites of ubiquitination
      were identified in GST-Ubc5 and four sites in ubiquitin. Assignments were
      confirmed by AI ECD or IRMPD. The Gly-Gly modification is stable and both tandem
      mass spectrometric techniques are suitable, providing extensive sequence coverage
      and retention of the modification on backbone fragments.

PMID- 15571351
TI  - Direct N-glycan profiling in the presence of tryptic peptides on MALDI-TOF by
      controlled ion enhancement and suppression upon glycan-selective derivatization.
AB  - Even though the formidably laborious and time-consuming nature of oligosaccharide
      analysis limits certain attempts to analyze the glycosylation profile, the
      significant elucidation of carbohydrate modifications is largely dependent on it.
      Aiming to substantially improve the sample preparation procedure, a novel
      protocol allowing glycan-specific detection in the presence of other species,
      such as tryptic peptides, on MALDI-TOF was proposed and then evaluated. The new
      protocol is based on the concept that the desorption/ionization efficiency of
      glycans could be selectively and substantially enhanced while drastically
      suppressing the other ion species upon glycan-selective derivatization. A series
      of known and novel labeling reagents, all of which carry hydrazide functionality
      to allow glycan-specific derivatization, were prepared and evaluated in terms of
      their abilities to enhance the detection sensitivity of glycans, suppress ions of
      other contaminants (e.g., peptides), and detect acidic oligosaccharides. Several
      novel reagents that possess hydrophobic residue(s) together with quaternary
      ammonium/pyridinium or guanidino functionalities significantly enhanced the
      detection sensitivity of oligosaccharides. When enzymatically deglycosylated
      tryptic ovalbumin digest was directly derivatized by these reagents and subjected
      to MALDI-TOF analysis without any prior purification, we observed that a single
      type of analyte ion (labeled glycan) could suppress a large majority of peptide
      ions while allowing a low-femtomole level detection of oligosaccharides. The
      efficacy of this approach was further evaluated using several other model
      glycoproteins, including alpha(1)-acid glycoprotein that contains a variety of
      sialylated oligosaccharides.

PMID- 15571352
TI  - Picogram per liter level determination of estrogens in natural waters and
      waterworks by a fully automated on-line solid-phase extraction-liquid
      chromatography-electrospray tandem mass spectrometry method.
AB  - The present work describes a novel, fully automated method, based on on-line
      solid-phase extraction-liquid chromatography-electrospray tandem mass
      spectrometry (SPE-LC-ESI-MS-MS), which allows the unequivocal identification and
      quantification of the most environmentally relevant estrogens (estradiol,
      estrone, estriol, estradiol-17-glucuronide, estradiol-17-acetate, estrone-3
      sulfate, ethynyl estradiol, diethylstilbestrol) in natural and treated waters at
      levels well below those of concern (limits of quantification between 0.02 and
      1.02 ng/L). The method is highly precise, with relative standard deviations
      varying between 1.43 and 3.89%, and accurate (recovery percentages >74 %). This
      method was used to track the presence and fate of the target compounds in a
      waterworks and to evaluate the removal efficiency of the treatment processes
      applied. Only estrone and estrone-3-sulfate were detected in the river water used
      as source (at 0.68 and 0.33 ng/L, respectively). After progressive removal
      through the various treatment steps, none of them were detected in the finished
      drinking water. In addition to selectivity, sensitivity, repeatability, and
      automation (up to 15 samples plus 6 calibration solutions and 1 blank can be
      analyzed unattended), this technique offers fairly high throughput (analysis time
      per sample is 60 min), low time and solvent consumption, and ease of use.

PMID- 15571353
TI  - Preparation and application of methacrylate-based cation-exchange monolithic
      columns for capillary ion chromatography.
AB  - Polymer-based strong cation-exchange monolithic capillary columns with different
      capacities were constructed for ion chromatography by radical polymerization of
      glycidyl methacrylate (GMA) and ethylene dimethacrylate in a 250-microm-i.d.
      fused-silica capillary and its subsequent sulfonation based on ring opening of
      epoxides with 1 M Na(2)SO(3). The cation-exchange capacities can easily and
      reproducibly be controlled in the range of up to 300 microequiv/mL by changing
      the immersion time of the epoxy-containing polymer in the Na(2)SO(3) solution.
      The chromatographic performance of the produced monolithic capillary columns was
      evaluated through the separation of a model mixture of common cations such as
      Na(+), NH(4)(+), K(+), Mg(2+), and Ca(2+). As an example, these cations could be
      well separated from one another on a 15-cm-long cation-exchange monolithic column
      (column volume, 7.4 microL) with a capacity of 150 microequiv/mL by elution with
      10 mM CuSO(4). The pressure drop of this 15-cm column was approximately 1 MPa at
      a normal linear velocity of 1 mm/s (a flow rate of 3 microL/min), and the numbers
      of theoretical plates for the cations were above 3000 plates/15 cm. This GMA
      based cation-exchange monolithic column could withstand high linear velocities of
      at least 10 mm/s. Over a period of at least two weeks of continuous use, no
      significant changes in the selectivity and resolution were observed. The
      applicability of a flow rate gradient elution and the feasibility of direct
      injection determination of major cations in human saliva sample were also
      presented.

PMID- 15571354
TI  - High-performance affinity monolith chromatography: development and evaluation of
      human serum albumin columns.
AB  - Several immobilization methods were explored for the preparation of high
      performance affinity monolithic columns containing human serum albumin (HSA).
      These monoliths were based on a copolymer of glycidyl methacrylate and ethylene
      dimethacrylate. In one method, the epoxy groups of this copolymer were used
      directly for the immobilization of HSA through its amine residues (i.e., the
      epoxy method); in other approaches, these epoxy groups were converted to diols
      for later use in the carbonyldiimidazole, disuccinimidyl carbonate, and Schiff
      base methods. Each HSA monolith was evaluated in terms of its total protein
      content and its retention of several model compounds, including (R/S)-warfarin
      and D/L-tryptophan. The greatest amount of immobilized HSA was obtained by the
      Schiff base method, whereas the epoxy method gave the lowest protein content. The
      Schiff base method also gave the best resolution in chiral separations of (R/S)
      warfarin and D/L-tryptophan. All of the immobilization methods gave similar
      relative activities for HSA in its binding to (R)- and (S)-warfarin, but some
      differences were noted in the activity of the immobilized HSA for D- and L
      tryptophan. The efficiency of these monoliths was found to be greater than that
      of silica-based HSA columns for (R/S)-warfarin (i.e., analytes with high
      retention), but little or no difference was seen for D- and L-tryptophan
      (analytes with weak retention).

PMID- 15571355
TI  - Boosting sensitivity of organic vapor detection with silicone block polyimide
      polymers.
AB  - We demonstrate that silicone block polyimide polymers have an unusually high
      sensitivity to nonpolar organic vapors, including chlorinated organic solvent
      vapors. When 0.18-5.34-microm-thick films of silicone block polyimide polymers
      were deposited onto 10-MHz thickness shear mode (TSM) oscillators, these films
      were implemented to detect parts-per-billion concentrations of trichloroethylene
      (TCE) with a detection sensitivity of 0.5-23.5 Hz per 500 ppb of vapor. With a
      film thickness of 3.4 microm (91.5-kHz frequency shift upon film deposition),
      optimized for the minimal sensor noise of 0.04 Hz, the calculated detection limit
      of sensor response (S/N = 3) was 3 ppb of TCE. Detection limits for other
      chlorinated organic solvent vapors, such as perchloroethylene (PCE), cis-1,2
      dichloroethylene (DCE), trans-1,2-DCE, 1,1-DCE, and vinyl chloride (VC) were 0.6,
      6, 6, 11, and 13 ppb, respectively. Assuming only the mass-loading response when
      deposited onto the TSM devices, silicone block polyimide polymers have partition
      coefficients of over 200 000 to parts-per-billion concentrations of TCE that make
      them at least 100 times more sensitive than other known polymers for TCE
      detection. We observed that unlike conventional polyimides, water sensitivity of
      the new hybrid polyimides is suppressed because of the silicone soft block. Water
      sensitivity is comparable with the sensor response to nonpolar organic vapors.
      The high sensitivity and long-term stability of these sensor materials make them
      attractive for ultrasensitive practical sensors.

PMID- 15571356
TI  - LC-MS/MS analysis of peptides with methanol as organic modifier: improved limits
      of detection.
AB  - With the advent of soft ionization methods such as MALDI and ESI, mass
      spectrometry has become the most important technique for the analysis of proteins
      and peptides. ESI-MS is often preceded by separation of the peptide sample by
      reversed-phase liquid chromatography (LC). Acetonitrile (ACN) is the most
      commonly employed organic solvent in LC-ESI-MS analysis of peptides. In this
      report, we demonstrate that the use of methanol (MeOH) as the organic modifier
      improves the detection limits for analysis of peptide mixtures such as those
      found in tryptic digests of proteins. A nanoLC-ESI-quadrupole ion trap instrument
      (LCQ Deca, ThermoFinnigan) was used to analyze peptide standards, protein digests
      of known concentrations, and tryptic digests of 2-DGE-separated proteins. MeOH
      displayed excellent chromatographic performance (separation and sensitivity), and
      shorter gradient times were possible for chromatographic separation with MeOH
      versus ACN. Sensitivity levels of a few hundred attomoles were achieved with
      MeOH; those levels could not be achieved with ACN. In addition, MeOH-based nanoLC
      MS/MS yielded superior results for the analysis of digests of 2-DGE-separated
      proteins. For the 14 protein spots analyzed, the success rate of protein
      identification with MeOH-based nanoLC-ESI-MS/MS was 100%, with multiple proteins
      identified in several of the spots. In contrast, ACN-based procedure failed to
      identify any proteins in 21% of the spots and overall identified 33% fewer
      proteins than the MeOH-based procedure. In summary, higher sensitivity and
      shorter gradient times make MeOH an excellent organic modifier for the use in
      nanoLC-ESI-MS/MS analysis of peptides.

PMID- 15571357
TI  - Hybridization enhancement using microfluidic planetary centrifugal mixing.
AB  - DNA microarrays produce their greatest sensitivities when hybridized using
      concentrated samples and effective mixing; however, these goals have proved
      elusive to combine. If samples are diluted enough to fill larger chambers, then
      mixing works well using either pumping or gravity with rotation, although
      sensitivities will suffer. Various techniques for mixing concentrated samples in
      small thin chambers have been proposed; however, they often leave streaks or
      scars, and their reusable components require careful cleaning. Here we introduce
      a versatile new microfluidics platform, a two-axis centrifuge whose fluidic
      chambers rotate in a planetary relationship to a radial gravitational field. This
      paradigm readily overcomes surface and viscous forces even in chambers only 50
      microm thin. Thin chambers obviate the need for sample dilution and increase
      sensitivities and dynamic ranges 10-fold. In comparisons against conventional
      mixing using the same 10 microg of starting total RNA on 22 000-probe arrays, 10
      000 more usable signals rose above the noise. In other experiments, planetary
      mixing was able to produce comparable results while using only one-tenth the
      starting sample. The benefits of planetary mixing include sample conservation,
      shorter hybridizations, less reliance on amplification, and the ability to
      quantify many gene signals otherwise obscured by noise.

PMID- 15571358
TI  - Electrotransfection of mammalian cells using microchannel-type electroporation
      chip.
AB  - Transfection of DNA molecules into mammalian cells with electric pulsations,
      which is so-called electroporation, is a powerful and widely used method that can
      be directly applied to gene therapy. However, very little is known about the
      basic mechanisms of DNA transfer and cell response to the electric pulse. We
      developed a microelectroporation chip with poly(dimethylsiloxane) (PDMS) to
      investigate the mechanism of electroporation as a first step of DNA transfer and
      to introduce the benefits of miniaturization into the genetic manipulation. The
      microelectroporation chip has a microchannel with a height of 20 microm and a
      length of 2 cm. Owing to the transparency of PDMS, we could in situ observe the
      uptake process of propidium iodide (PI) into SK-OV-3 cells, which shows promise
      in visualization of gene delivery in living cells. We also noticed the geometric
      effect on the degree of electroporation in microchannels with diverse channel
      width. This experimental result shows that the geometry can be another parameter
      to be considered for the electroporation when it is performed in microchannels
      with an exponential decaying pulse generator. Cell culturing is possible within
      the microelectroporation chip, and we also successfully transfected SK-OV-3 cells
      with enhanced green fluorescent protein genes, which demonstrates the feasibility
      of the microelectroporation chip in genetic manipulation.

PMID- 15571359
TI  - Aptasensor development: elucidation of critical parameters for optimal aptamer
      performance.
AB  - Aptamers are synthetic oligonucleotides specifically selected to bind a certain
      target. Thanks to their high affinity and sensitivity, aptamers appear as
      alternative candidates to antibodies for analytical devices and several assays
      have been reported. However, and contrary to what happens with DNA probes, the
      aptamers' ability to bind their targets depends on folding and 3-D structure,
      which may be affected by the incubation conditions and buffer composition. In
      this report, a systematic evaluation of the parameters with potential effect on
      the ELAA (Enzyme Linked Aptamer Assay) performance has been carried out.
      Additionally, diverse ELAA and mixed ELISA/ELAA formats exploiting the thrombin
      binding aptamer have been optimized and their efficiencies compared. ELAA results
      have been confirmed using nuclear magnetic resonance, electrophoresis, and
      surface plasmon resonance. Our results indicate that parameters such as
      immobilization strategy, incubation time/temperature, and buffer composition
      should be optimized for each aptamer as they affect folding and, thus, binding
      efficiency. Among the studied assays, the mixed ELISA/ELAA sandwich formats
      showed the lowest limit of detection observed (<1 nM thrombin), while a
      competition ELAA appeared as the best assay in terms of high sensitivity (1.8 nM)
      and short assay time (1 h, 30 min). The elucidation of optimal parameters for
      assay performance reported here clearly indicates that aptamers are unique
      structures. Formation of the 3-D structures required for target binding is
      influenced by variable parameters, and unlike DNA/antibody based assays, there
      are no general recommendations, with each assay requiring individual optimization
      of parameters.

PMID- 15571360
TI  - Intracellular pH sensors based on surface-enhanced raman scattering.
AB  - We present the development of nanoscale pH sensors based on functionalized silver
      nanoparticles and surface-enhanced Raman scattering (SERS). The SERS spectrum
      from individual silver nanoparticle (50-80 nm in diameter) clusters
      functionalized with 4-mercaptobenzoic acid shows a characteristic response to the
      pH of the surrounding solution and is sensitive to pH changes in the range of 6
      8. Measurements from nanoparticles incorporated in living Chinese hamster ovary
      cells demonstrate that the nanoparticle sensors retain their robust signal and
      sensitivity to pH when incorporated into a cell.

PMID- 15571361
TI  - Development of a bioluminescence resonance energy-transfer assay for estrogen
      like compound in vivo monitoring.
AB  - A new bioluminescence resonance energy transfer (BRET) homogeneous assay to
      evaluate the presence of estrogen-like compounds has been developed and
      optimized. The assay is based on the direct evaluation of estrogen alphareceptor
      (ERalpha) homodimerization as a result of estrogen-like compound binding. ERalpha
      monomer was genetically fused either to Renilla luciferase (Rluc) or to enhanced
      yellow fluorescent protein (EYFP). In the presence of estrogens, ERalpha
      dimerization brings Rluc and EYFP molecules close enough for an energy transfer.
      An in vitro BRET assay was first developed using purified fusion proteins
      (ERalpha-Rluc and ERalpha-EYFP) expressed in Escherichia coli to evaluate and
      optimize the analytical performances of the assay in the presence of 17-beta
      estradiol. The "in vivo" BRET quantitative assay was then developed by
      coexpressing the two fusion proteins in live HepG2 cells. The assay can be
      performed in 96-well microplate format with a 30-min incubation and allows
      detection with adequate accuracy and precision of as low as 1 nM of 17-beta
      estradiol. This new "in vivo" BRET assay allows evaluating the estrogen-like
      activity and synthetic xenoestrogens from biological and environmental samples.

PMID- 15571362
TI  - Determination of ligand-protein dissociation constants by electrospray mass
      spectrometry-based diffusion measurements.
AB  - A novel approach for the quantification of ligand-protein interactions is
      presented. Electrospray ionization mass spectrometry (ESI-MS) is used to monitor
      the diffusion behavior of noncovalent ligands in the presence of their protein
      receptors. These data allow the fraction of free ligand in solution to be
      determined, such that the corresponding dissociation constants can be calculated.
      A set of conditions is developed that provides an "allowable range" of
      concentrations for this type of assay. The method is tested by applying it to two
      different inhibitor-enzyme systems. The dissociation constants measured for
      benzamidine-trypsin and for N,N',N' '-triacetylchitotriose-lysozyme are (50 +/-
      10) and (6 +/- 1) mM, respectively. Both of these results are in good agreement
      with previous data from the literature. In contrast to traditional ESI-MS-based
      methods, the approach used in this work does not rely on the preservation of
      specific solution-type noncovalent interactions in the gas phase. It is shown
      that this method allows an accurate determination of dissociation constants, even
      in cases in which the ion abundance ratio of free to ligand-bound protein in ESI
      MS does not reflect the corresponding concentration ratio in solution.

PMID- 15571363
TI  - Asymmetric membrane fiber-based carbon dioxide removal devices for ion
      chromatography.
AB  - The application of hollow and filament-filled single asymmetric membrane fibers,
      consisting of a thin silicone layer on a tubular microporous support, for
      removing CO(2) in suppressed ion chromatography effluents is described. With
      appropriate choice of the removal device and operating conditions, the CO(2) can
      be essentially quantitatively (99+%) removed. For carbonate-based eluents, the
      use of such devices greatly reduces or eliminates the water dip, permitting
      better quantitation of poorly retained anions that elute close to the dip, allows
      practical gradient chromatography, and improves noise levels and attainable
      detection limits. In hydroxide eluent chromatography, the device largely removes
      the response from CO(2) present in the samples; this greatly aids atmospheric
      trace gas analysis by IC. Device dimensions are such that the dispersion
      introduced by the device is small.

PMID- 15571364
TI  - Multivariate curve resolution applied to the analysis and resolution of two
      dimensional [1H,15N] NMR reaction spectra.
AB  - Multivariate curve resolution is proposed for the study of complex chemical
      reactions monitored by two-dimensional (2D) NMR spectroscopy. In particular, in
      this work, multivariate curve resolution is applied to the study of the reaction
      between (15)N-labeled cisplatin and the amino acid-nucleotide hybrid (Phac-Met
      linker-p(5')dG). At several stages of the reaction, 2D [(1)H,(15)N] HSQC NMR
      spectra were acquired and stored in data matrices. In a first step, multivariate
      curve resolution was applied to analyze individually each one of these 2D
      spectra, allowing the resolution of the corresponding (1)H and (15)N one
      dimensional correlation spectra. In a second step, the whole set of 2D spectra
      recorded along the reaction were simultaneously analyzed by multivariate curve
      resolution, allowing the resolution of the kinetic concentration profiles and of
      the pure 2D NMR spectra of each of the species detected along the reaction.
      Results finally obtained confirmed previously postulated reaction mechanisms
      involving the existence of two monofunctional adducts and of two bifunctional
      adducts, with the structure of one of them not completely resolved.

PMID- 15571365
TI  - Radionuclide imaging of miniaturized chemical analysis systems.
AB  - We propose radionuclide imaging as a valuable tool for the study of molecular
      interactions in miniaturized systems for chemical analysis. Sensitive and
      quantitative imaging can be performed with compounds labeled with short-lived
      positron-emitting radionuclides, such as (11)C and (68)Ga, within selected parts
      of the system. Radionuclide imaging is not restricted to transparent materials
      since the relatively energetic positrons can penetrate high optical density
      materials. Experimentally, a radiotracer is introduced into the object of study,
      which is subsequently placed on a phosphor storage plate. After exposure, the
      plate is scanned with a laser and a digital, quantitative image can be
      reconstituted. To demonstrate the concept, three types of microstructures suited
      for integration in chemical analysis systems were imaged with (11)C- and (68)Ga
      labeled tracers. The influence of factors such as geometry of the object and type
      of radionuclide on resolution and sensitivity was investigated. The resolution
      ranged from 0.9 to 2.7 mm (fwhm). Measuring low amounts of radioactivity in the
      three structures, 2-20 Bq could be detected, which corresponded to 2.3-500 amol
      or 2.4-110 pM tracer. The imaging approach was applied to study analyte
      concentration and sample dilution effects on the performance of a capillary
      extraction column integrated in an automated LC-ESI-MS system. The utility of the
      technique was further illustrated by imaging of microchannels in a zeonor plastic
      compact disk and in a poly(dimethylsiloxane) material for the study of
      nonspecific peptide adsorption.

PMID- 15571366
TI  - Electrogenerated chemiluminescence. 80. C-reactive protein determination at high
      amplification with [Ru(bpy)3]2+-containing microspheres.
AB  - Biotinylated anti-C-reactive protein (CRP) species were attached to the surface
      of streptavidin-coated magnetic beads (MB) and avidin-coated polystyrene
      microspheres/beads (PSB) entrapping a large number of electrogenerated
      chemiluminescence (ECL) labels ( approximately 10(9)
      Ru(bpy)(3)[B(C(6)F(5))(4)](2)/bead) to form anti-CRP<-->MB and Ru(II)
      subsetPSB/avidin<-->anti-CRP conjugates, respectively. Sandwich-type Ru(II)
      subsetPSB/avidin<-->anti-CRP CRP anti-CRP<-->MB aggregates were formed when
      Ru(II) subsetPSB/avidin<-->anti-CRP was mixed with anti-CRP<-->MB conjugates in
      the presence of analyte CRP. The newly formed aggregates were magnetically
      separated from the reaction media and dissolved in MeCN containing tri-n
      propylamine as an ECL coreactant. ECL was carried out with a potential scan from
      0 to 2.8 V vs Ag/Ag(+), and the ECL intensity was found to be proportional to the
      analyte CRP concentration over the range of 0.010-10 mug/mL. The CRP
      concentration of an unknown human plasma specimen was measured by the standard
      addition method based on this technique. Elimination of the nonspecific
      adsorption of the CRP system with several different blocking agents was also
      studied, and 2.0% bovine serum albumin was found to be best.

PMID- 15571367
TI  - Using nonequilibrium capillary electrophoresis of equilibrium mixtures for the
      determination of temperature in capillary electrophoresis.
AB  - Until now, all methods for temperature sensing in capillary electrophoresis (CE)
      relied on molecular probes with temperature-dependent spectral/optical
      properties. Here we introduce a nonspectroscopic approach to determining
      temperature in CE. It is based on measuring a temperature-dependent rate constant
      of complex dissociation by means of a kinetic CE method known as nonequilibrium
      capillary electrophoresis of equilibrium mixtures (NECEEM). Conceptually, a
      calibration curve of "the rate constant versus temperature" is built using NECEEM
      and a CE instrument with a reliable temperature control or, alternatively, a
      nonelectrophoretic method, such as surface plasmon resonance. The calibration
      curve is then used to find the temperature during CE in the same buffer but with
      another CE apparatus or under otherwise different conditions (cooling efficiency,
      length and diameter of the capillary, electrical field, etc.). In this proof-of
      principle work, we used the dissociation of a protein-DNA complex to demonstrate
      that the NECEEM-based temperature determination method allows for temperature
      determination in CE with a precision of 2 degrees C. Then, we applied the NECEEM
      based temperature determination method to study heat dissipation efficiency in CE
      instruments with active and passive cooling of the capillary. The
      nonspectroscopic nature of the method makes it potentially applicable to
      nonspectroscopic detection schemes, e.g. electrochemical detection. A "kinetic
      probe" can be coloaded into the capillary along with a sample for in situ
      temperature measurements. Higher order chemical reactions can also be used for
      temperature sensing, provided a kinetic CE method for measuring a corresponding
      rate constant is available.

PMID- 15571368
TI  - Surface-enhanced vibrational microspectroscopy of fulvic acid micelles.
AB  - Micro-Raman spectroscopy, infrared absorption microspectroscopy, and AFM images
      of nano- or microsized micelles formed by fulvic acid (FA) solutions, prepared at
      different pHs, and cast on glass slides or gold island films, are reported. FA
      films cast on gold islands are characterized by surface-enhanced infrared
      absorption (SEIRA), surface-enhanced infrared reflection absorption, and surface
      enhanced Raman scattering (SERS). Based on spectral evidence, it is expected that
      the chemisorption of FA on gold island films takes place through thiol groups,
      which become more active as pH increases. The SEIRA spectra of these films show
      increased peak intensity, as well as improved band resolution. Microspectroscopy
      SERS studies show that, at pH 5, FA form small aggregates on gold surfaces. At pH
      8, FA tends to expand due to electrostatic repulsion, giving rise to a fractal
      surface composed of different domains. SERS studies of these domains reveal that
      the most polar molecules are located on the external faces. At pH 11, fractal
      conformations are even more pronounced and give rise to radial patterned
      structures. At this pH, the position of fulvic acid molecules in the fractal
      micelles is the same as observed at pH 8. In this way, SERS can be viewed as a
      powerful tool for the analysis of the composition, apparent contribution of the
      surface functional groups of FA films, and the FA building blocks (i.e.,
      catechol, gallic, salicylic, or ftalic acids) in the structures of these
      materials.

PMID- 15571369
TI  - Electrochemical coding for multiplexed immunoassays of proteins.
AB  - An electrochemical immunoassay protocol for the simultaneous measurements of
      proteins, based on the use of different inorganic nanocrystal tracers is
      described. The multiprotein electrical detection capability is coupled to the
      amplification feature of electrochemical stripping transduction (to yield fmol
      detection limits) and with an efficient magnetic separation (to minimize
      nonspecific adsorption effects). The multianalyte electrical sandwich immunoassay
      involves a dual binding event, based on antibodies linked to the nanocrystal tags
      and magnetic beads. Carbamate linkage is used for conjugating the hydroxyl
      terminated nanocrystals with the secondary antibodies. Each biorecognition event
      yields a distinct voltammetric peak, whose position and size reflects the
      identity and level, respectively, of the corresponding antigen. The concept is
      demonstrated for a simultaneous immunoassay of beta(2)-microglobulin, IgG, bovine
      serum albumin, and C-reactive protein in connection with ZnS, CdS, PbS, and CuS
      colloidal crystals, respectively. These nanocrystal labels exhibit similar
      sensitivity. Such electrochemical coding could be readily multiplexed and scaled
      up in multiwell microtiter plates to allow simultaneous parallel detection of
      numerous proteins or samples and is expected to open new opportunities for
      protein diagnostics and biosecurity.

PMID- 15571370
TI  - Determination of methylmercury in environmental matrixes by on-line flow
      injection and atomic fluorescence spectrometry.
AB  - The precision and bias of monomethylmercury (MMHg) determinations in
      environmental samples can be improved by directly coupling and automating the
      numerous steps involved with analysis of this toxic Hg species. We developed a
      simple and robust mercury speciation analyzer (MSA) for measurement of MMHg in
      environmental matrixes. This on-line hyphenated system couples the main
      analytical steps, including sample introduction, aqueous-phase ethylation, Tenax
      preconcentration, and gas chromatographic separation, to cold vapor atomic
      fluorescence detection and data acquisition. Here we describe the MMHg-MSA,
      present results of laboratory optimization and performance tests, and compare the
      reproducibility between dual analytical channels. With alternating sample
      concentration and analysis, a dual-channel system permits six high-accuracy MMHg
      determinations per hour. Additional advantages compared to the traditional manual
      method include ease of operation and high precision (<5% relative standard
      deviation). The MSA is applicable to the determination of MMHg in various
      environmental matrixes, and it can be fully automated. This method was validated
      by analysis of MMHg in certified reference materials of sediment and biological
      tissue. Estimated detection limits for MMHg with the MSA are approximately 0.01
      ng g(-1) for a 0.1-g sample of dry sediment or fish and approximately 0.01 ng L(
      1) for 0.15 L of water.

PMID- 15571371
TI  - Hydride generation interface for speciation analysis coupling capillary
      electrophoresis to inductively coupled plasma mass spectrometry.
AB  - A novel hydride generation (HG) interface for coupling capillary electrophoresis
      (CE) with inductively coupled plasma mass spectrometry (ICPMS) is presented in
      this work. The CE-HG-ICPMS interface was applied to the separation and
      quantitation of common arsenic species. Lack of a commercially available HG
      interface for CE-ICPMS led to a three concentric tube design allowing alleviation
      of back pressure commonly observed in CE-HG-ICPMS. Due to the high sensitivity
      and element-specific detection of ICPMS, quantitative analysis of As(III), As(V),
      monomethylarsonic acid, and dimethylarsinic acid was achieved. Optimization of CE
      separation conditions resulted in the use of 20 mmol L(-1) sodium borate with 2%
      osmotic flow modifier (pH 9.0) and -20 kV applied potential for baseline
      resolution of each arsenic species in the shortest time. Hydride generation
      conditions were optimized through multiple electrophoretic separation analyses
      with 5% HCl and 3% NaBH(4) (in 0.2% NaOH) determined to be the optimum
      conditions. After completion of system optimization, detection limits obtained
      for the arsenic species were less than 40 ng L(-1) with electromigration time
      precision less than 1% within a total analysis time of 9.0 min. Finally, the
      interface was used for speciation analysis of arsenic in river and tap water
      samples.

PMID- 15571372
TI  - Quantitation of lysergic acid diethylamide in urine using atmospheric pressure
      matrix-assisted laser desorption/ionization ion trap mass spectrometry.
AB  - A quantitative method was developed for analysis of lysergic acid diethylamide
      (LSD) in urine using atmospheric pressure matrix-assisted laser
      desorption/ionization ion trap mass spectrometry (AP MALDI-ITMS). Following solid
      phase extraction of LSD from urine samples, extracts were analyzed by AP MALDI
      ITMS. The identity of LSD was confirmed by fragmentation of the [M + H](+) ion
      using tandem mass spectrometry. The quantification of LSD was achieved using
      stable-isotope-labeled LSD (LSD-d(3)) as the internal standard. The [M + H](+)
      ion fragmented to produce a dominant fragment ion, which was used for a selected
      reaction monitoring (SRM) method for quantitative analysis of LSD. SRM was
      compared with selected ion monitoring and produced a wider linear range and lower
      limit of quantification. For SRM analysis of samples of LSD spiked in urine, the
      calibration curve was linear in the range of 1-100 ng/mL with a coefficient of
      determination, r(2), of 0.9917. This assay was used to determine LSD in urine
      samples and the AP MALDI-MS results were comparable to the HPLC/ ESI-MS results.

PMID- 15571373
TI  - Dendrimers with both polar and apolar nanocontainer characteristics.
AB  - Amphiphilic dendrimers with a custom-designed biaryl repeat unit have been
      synthesized. These dendrimers afford hydrophobic nanocontainers in polar solvents
      and hydrophilic nanocontainers in apolar solvents. These container properties
      were investigated using dye incorporation studies. The aggregation states of
      these dendrimers are also reported using DLS studies.

PMID- 15571374
TI  - Near-infrared fluorescence microscopy of single-walled carbon nanotubes in
      phagocytic cells.
AB  - The uptake of pristine single-walled carbon nanotubes into macrophage-like cells
      has been studied using the nanotubes' intrinsic near-infrared fluorescence.
      Macrophage samples that have been incubated in growth media containing suspended
      single-walled nanotubes show characteristic nanotube fluorescence spectra. The
      fluorescence intensities increase smoothly with incubation time and external
      nanotube concentration. Near-infrared fluorescence microscopy at wavelengths
      above 1100 nm provides high contrast images indicating localization of nanotubes
      in numerous intracellular vesicles. Nanotube uptake appears to occur through
      phagocytosis. Population growth of macrophage cultures is unaffected by exposure
      to single-walled nanotube concentrations of ca. 4 mug/mL for up to 96 h.

PMID- 15571375
TI  - Microarray platform for profiling enzyme activities in complex proteomes.
AB  - Activity-based protein profiling (ABPP) is a chemical method that utilizes active
      site-directed probes to determine the functional state of enzymes in complex
      proteomes. Probe-labeled enzymes are typically detected by in-gel fluorescence
      scanning, a robust technique that nonetheless exhibits some key deficiencies,
      including limited sensitivity and resolution, as well as ambiguity regarding the
      molecular identity of the enzymes under investigation. Here, we report a
      microarray platform for ABPP that addresses these limitations. In this platform,
      proteomes are treated with ABPP probes in solution, after which labeled enzymes
      are captured and visualized on glass slides displaying an array of anti-enzyme
      antibodies. We show that ABPP microarrays exhibit superior sensitivity and
      resolution compared to gel-based methods, permitting the parallel analysis of
      several enzyme activities in proteomes, including cancer-associated proteases
      such as urokinase, matrix metalloproteinase-9, and prostate-specific antigen.

PMID- 15571376
TI  - A strong positive dendritic effect in a peptide dendrimer-catalyzed ester
      hydrolysis reaction.
AB  - The contribution of the dendritic structure in catalysis of ester hydrolysis was
      investigated with a systematic peptide dendrimer series of increasing generation
      number (G1-G4) containing a catalytic consensus sequence His-Ser in all branches.
      A strong positive dendritic effect was observed with up to 100-fold increased
      histidine reactivity between G1 and G4. Kinetic studies and isothermal
      calorimetric titration experiments showed that the strong positive dendritic
      effect resulted from cooperativity between binding and catalysis.

PMID- 15571377
TI  - Fluorinated imidazoles as proton carriers for water-free fuel cell membranes.
AB  - We propose an alternative new material (2,4,5-trifluoroimidazole impregnated
      Nafion) for use as a high-temperature, water-free membrane for proton-exchange
      membrane fuel cells. This material has been tested computationally using
      molecular dynamics and quantum mechanics techniques, leading to an estimated
      conductivity of approximately 0.06 S/cm at 177 degrees C. This material overcomes
      the weakness of the imidazole-impregnated membranes, i.e., the poisoning of the
      Pt electrode. We find that 2,4,5-trifluoroimidazole binds weakly to platinum
      surfaces, so poisoning is not expected.

PMID- 15571378
TI  - DNA-nanotube artificial ion channels.
AB  - There is considerable interest in developing chemical devices that mimic the
      function of biological ion channels. We recently described such a device, which
      consisted of a single conically shaped gold nanotube embedded within a polymeric
      membrane. This device mimicked one of the key functions of voltage-gated ion
      channels: the ability to strongly rectify the ionic current flowing through it.
      The data obtained were interpreted using a simple electrostatic model. While the
      details are still being debated, it is clear that ion-current-rectification in
      biological ion channels is more complicated and involves physical movement of an
      ionically charged portion of the channel in response to a change in the
      transmembrane potential. We report here artificial ion channels that rectify the
      ion current flowing through them via this "electromechanical" mechanism. These
      artificial channels are also based on conical gold nanotubes, but with the
      critical electromechanical response provided by single-stranded DNA molecules
      attached to the nanotube walls.

PMID- 15571379
TI  - Initial observation of magnetization hysteresis and quantum tunneling in mixed
      manganese-lanthanide single-molecule magnets.
AB  - The preparation of a new family of mixed transition metal/lanthanide clusters is
      reported. The reaction of [Mn3O(O2CPh)6(py)2(H2O)] with Ln(NO3)3 (Ln = Nd, Gd,
      Dy, Ho, and Eu) in a 1:2 molar ratio in MeOH/MeCN (1:20 v/v) leads to dark
      crystals in 55-60% isolated yield of complexes all containing the [Mn11Ln4]45+
      core. The Dy compound has been found to give out-of-phase AC susceptibility
      signals, suggesting it might be a single-molecule magnet (SMM). This was
      confirmed by the observation of magnetization hysteresis loops. An Arrhenius plot
      constructed from magnetization decay data gave a barrier to relaxation of 9.3 K
      and showed the temperature-independent relaxation at very low temperatures
      indicative of quantum tunneling of magnetization. This is the initial
      demonstration of hysteresis and quantum behavior in a mixed 3d/4f SMM.

PMID- 15571380
TI  - Stannylative cycloaddition of enynes catalyzed by palladium-iminophosphine.
AB  - Palladium-iminophosphine complex catalyzes stannylative cycloaddition of
      conjugated enynes using hexabutyldistannoxane as a stannylating agent to afford
      highly substituted 3-alkenylphenylstannanes regioselectively. Stannylative cross
      cycloaddition reactions between different enynes or between enynes and diynes are
      also achieved. The reaction is successfully applied to a concise synthesis of
      alcyopterosin N, which has been isolated recently from sub-Antarctic soft coral,
      Alcyonium paessleri.

PMID- 15571381
TI  - Asymmetric alpha-alkylation of N'-tert-butanesulfinyl amidines. Application to
      the total synthesis of (6R,7S)-7-amino-7,8-dihydro-alpha-bisabolene.
AB  - A highly diastereoselective alpha-alkylation of N'-tert-butanesulfinyl amidines
      has been developed along with methods for converting the alkylation products to
      enantiomerically enriched amines that incorporate both alpha- and beta
      stereocenters. The utility of this chemistry is further demonstrated by the first
      asymmetric synthesis of the antimicrobial marine natural product (6R,7S)-7-amino
      7,8-dihydro-alpha-bisabolene.

PMID- 15571382
TI  - Site-specific incorporation of the mucin-type N-acetylgalactosamine-alpha-O
      threonine into protein in Escherichia coli.
AB  - Glycosylation is a prevalent posttranslational process capable of augmenting and
      modulating protein function. Efficient synthesis of high-purity, homogeneous
      glycoproteins is essential for the study of unique protein glycoforms and for the
      manufacture of therapeutically relevant forms. A promising new strategy for
      controlled in vivo synthesis of glycoproteins was recently established using
      suppressor tRNA technology. Using an evolved tRNA aminoacyl synthetase-tRNA pair
      from Methanococcus jannaschii, the glycosyl amino acid, N-acetylglucosamine-beta
      O-serine (GlcNAc-beta-Ser), was site-specifically introduced into proteins
      cotranslationally in Escherichia coli. Herein, we report the evolution of a new
      tRNA aminoacyl synthetase-tRNA pair that has expanded the repertoire of
      glycoproteins that can be expressed in E. coli to contain the other major O
      linked glycan, N-acetylgalactosamine-alpha-O-threonine (GalNAc-a-Thr).

PMID- 15571383
TI  - Cell-specific delivery of a chemotherapeutic to lung cancer cells.
AB  - We report that lung cancer-targeting peptides isolated from a peptide library can
      be used to deliver an active chemotherapeutic in a cell-specific fashion. The
      peptides were removed from the context of the phage and placed on a pegylated
      tetrameric scaffold. The tetrameric peptides were shown to block uptake of their
      cognate phage. The tetrameric peptides were coupled to doxorubicin, and their
      cytotoxicity against a panel of different cell lines was tested. Our data
      demonstrate that these targeting peptides can deliver an active anticancer agent
      in a cell-specific fashion, resulting in an increase of the therapeutic index of
      the targeted drug compared to systemic delivery. The efficacy of the peptide
      conjugate correlates to the affinity of the targeting peptide for a particular
      cell line. As such, we have demonstrated that cell-specific targeted drugs can be
      synthesized, even when the cell surface target is unknown.

PMID- 15571384
TI  - The hydratase activity of malonate semialdehyde decarboxylase: mechanistic and
      evolutionary implications.
AB  - Malonate semialdehyde decarboxylase (MSAD) is a member of the tautomerase
      superfamily, a group of structurally homologous proteins that have a
      characteristic beta-alpha-beta-fold and a catalytic amino-terminal proline. In
      addition to its physiological decarboxylase activity, the conversion of malonate
      semialdehyde to acetaldehyde and carbon dioxide, the enzyme has now been found to
      display a promiscuous hydratase activity, converting 2-oxo-3-pentynoate to
      acetopyruvate, with a kcat/Km value of 6.0 x 102 M-1 s-1. Pro-1 and Arg-75 are
      critical for both activities, and the pKa of Pro-1 was determined to be
      approximately 9.2 by a direct 15N NMR titration. These observations implicate a
      decarboxylation mechanism in which Pro-1 polarizes the carbonyl oxygen of
      substrate by hydrogen bonding and/or an electrostatic interaction. Arg-75 may
      position the carboxylate group into a favorable orientation for decarboxylation.
      Both the hydratase activity and the pKa value of Pro-1 are shared with trans-3
      chloroacrylic acid dehalogenase, another tautomerase superfamily member that
      precedes MSAD in a bacterial degradation pathway for trans-1,3-dichloropropene.
      Hence, MSAD and CaaD could have evolved by divergent evolution from a common
      ancestral protein, retaining the necessary catalytic components for the conjugate
      addition of water.

PMID- 15571385
TI  - Direct observation of enantiomer discrimination of epoxides by chiral salen
      complexes using ENDOR.
AB  - Electron nuclear double resonance (ENDOR) spectroscopy was used to investigate
      the weak enantioselective binding between chiral salen complexes [VO(1)] ((R,R)-
      and (S,S)-vanadyl N,N'-bis(3,5-di-tert-butylsalcylidene)-1,2-cyclohexanediamine)
      and chiral epoxides (e.g., (R)-/(S)-propylene epoxide, 5) in frozen (10 K)
      solution. Differences in epoxide binding by enatiomers of [VO(1)] was evidenced
      by changes to the 1H epoxide derived peaks in the ENDOR spectra, such that (R,R)
      [VO(1)] + (R)-5 and (R,R)-[VO(1)] + (S)-5 yield noticeably different spectra.
      These changes were assigned to the small structural differences between the
      diastereomeric metal-epoxide adducts. Simulation of the spectra revealed
      differences in the VO...1Hepoxide distances for the diastereomeric pairs, which
      was confirmed by a complementary set of density functional theory (DFT)
      calculations. While the epoxide molecule is very weakly coordinated, ENDOR
      measurements of the racemic complex in racemic epoxide nevertheless indicated the
      preferential coordination of the (R)-5 to (R,R)-[VO(1)] (likewise (S)-(5) to
      (S,S)-[VO(1)]), which is favored over the binding of (S)-5 epoxide to (R,R)
      [VO(1)] (and likewise (R)-5 epoxide to (S,S)-[VO(1)]). This demonstrates the
      unique power of the ENDOR technique to resolve weak chiral interactions for which
      EPR spectroscopy alone lacks sufficient resolution.

PMID- 15571386
TI  - Oxonia-cope prins cyclizations: a facile method for the synthesis of
      tetrahydropyranones bearing quaternary centers.
AB  - A new cationic cascade reaction has been developed that produces 4
      tetrahydropyranones in good yield. The reaction is based on the facile 2-oxonia
      Cope rearrangement of allyl-substituted oxocarbenium ions. In the presence of a
      more nucleophilic silyl enol ether, such systems rearrange and cyclize to produce
      tetrahydropyranones. The substrates were prepared by silyl ketene acetal addition
      to ketenes. The rearrangement is compatible with tetrasubstituted silyl enol
      ethers, which result in the diastereoselective introduction of quaternary centers
      at the C3 position of the tetrahydropyran ring. The oxonia-Cope Prins
      rearrangement is a versatile new route to tetrahydropyrans.

PMID- 15571387
TI  - Total synthesis of (+/-)-pentacycloanammoxic acid.
AB  - The first total synthesis of (+/-)-pentacycloanammoxic acid/methyl ester (1), an
      unusual naturally occurring fatty acid from Candidatus Brocadia anammoxidans, has
      been accomplished by the sequence of reactions shown in Scheme 1. The C20
      structure of 1 was assembled with stereocontrol from three building blocks:
      cyclooctatetraene, 2-cyclopentenone, and 7-bromoheptanoic acid. The synthesis of
      1 confirms the proposed structure of 1. The mode of biosynthesis and absolute
      configuration have yet to be clarified.

PMID- 15571388
TI  - Stille coupling of stereochemically defined alpha-sulfonamidoorganostannanes.
AB  - Addition of tributylstannylmetallics to (R)-tert-butanesulfonimine derivatives of
      arylaldehydes provides alpha-sulfinamidostannanes with high (>98% de)
      diastereoselectivities. Oxidation of these compounds with m-CPBA gives alpha
      sulfonamidostannanes which undergo Pd/Cu-catalyzed Stille-type couplings with
      benzoyl chloride. Best yields are achieved using the electron-rich tris(2,4,6
      trimethoxyphenyl)phosphine as the ligand. Inversion of configuration at the
      benzylic carbon is observed.

PMID- 15571389
TI  - Correlated C-C and C-O bond conformations in saccharide hydroxymethyl groups:
      parametrization and application of redundant 1H-1H, 13C-1H, and 13C-13C NMR J
      couplings.
AB  - Methyl alpha- and beta-pyranosides of d-glucose and d-galactose 1-4 were prepared
      containing single sites of (13)C-enrichment at C4, C5, and C6 (12 compounds), and
      (1)H and (13)C[(1)H] NMR spectra were obtained to determine a complete set of J
      couplings ((1)J, (2)J, and (3)J) involving the labeled carbon and nearby protons
      and carbons within the exocyclic hydroxymethyl group (CH(2)OH) of each compound.
      In parallel theoretical studies, the dependencies of (1)J, (2)J, and (3)J
      involving (1)H and (13)C on the C5-C6 (omega) and C6-O6 (theta;) torsion angles
      in aldohexopyranoside model compounds were computed using density functional
      theory (DFT) and a special basis set designed to reliably recover the Fermi
      contact contribution to the coupling. Complete hypersurfaces for (1)J(C5,C6),
      (2)J(C5,H6)(R), (2)J(C5,H6)(S), (2)J(C6,H5), (2)J(C4,C6), (3)J(C4,H6)(R),
      (3)J(C4,H6)(S), and (3)J(C6,H4), as well as (2)J(H6)(R)(,H6)(S), (3)J(H5,H6)(R),
      and (3)J(H5,H6)(S), were obtained and used to parametrize new equations
      correlating these couplings to omega and/or theta;. DFT-computed couplings were
      also tested for accuracy by measuring J-couplings in (13)C-labeled 4,6-O
      ethylidene derivatives of d-glucose and d-galactose in which values of omega and
      theta; were constrained. Using a new computer program, Chymesa, designed to
      utilize multiple J-couplings sensitive to exocyclic CH(2)OH conformation, the
      ensemble of experimental couplings observed in 1-4 were analyzed to yield
      preferred rotamer populations about omega and theta;. Importantly, due to the
      sensitivity of some couplings, most notably (2)J(H6)(R)(,H6)(S), (2)J(C5,H6)(R),
      and (2)J(C5,H6)(S), to both omega and theta;, unique information on correlated
      conformation about both torsion angles was obtained. The latter treatment
      represents a means of evaluating correlated conformation in 1,6-linked
      oligosaccharides, since psi and theta; are redundant in these linkages. In the
      latter regard, multiple, redundant scalar couplings originating from both sides
      of the glycosidic linkage can be used collectively to evaluate conformational
      correlations between psi/theta; and C5-C6 bond rotamers.

PMID- 15571390
TI  - Isolation of fast purine nucleotide synthase ribozymes.
AB  - Here we report the in vitro selection of fast ribozymes capable of promoting the
      synthesis of a purine nucleotide (6-thioguanosine monophosphate) from tethered 5
      phosphoribosyl 1-pyrophosphate (PRPP) and 6-thioguanine ((6S)Gua). The two most
      proficient purine synthases have apparent efficiencies of 284 and 230 M(-1) min(
      1) and are both significantly more efficient than pyrimidine nucleotide synthase
      ribozymes selected previously by a similar approach. Interestingly, while both
      ribozymes showed good substrate discrimination, one ribozyme had no detectable
      affinity for 6-thioguanine while the second had a K(m) of approximately 80 muM,
      indicating that these ribozymes use considerably different modes of substrate
      recognition. The purine synthases were isolated after 10 rounds of selection from
      two high-diversity RNA pools. The first pool contained a long random sequence
      region. The second pool contained random sequence elements interspersed with the
      mutagenized helical elements of a previously characterized 4-thiouridine synthase
      ribozyme. While nearly all of the ribozymes isolated from this biased pool
      population appeared to have benefited from utilizing one of the progenitor's
      helical elements, little evidence for more complicated secondary structure
      preservation was evident. The discovery of purine synthases, in addition to
      pyrimidine synthases, demonstrates the potential for nucleotide synthesis in an
      'RNA World' and provides a context from which to study small molecule RNA
      catalysis.

PMID- 15571391
TI  - Kinetics and mechanism of *NO2 reacting with various oxidation states of
      myoglobin.
AB  - Nitrogen dioxide ((*)NO(2)) participates in a variety of biological reactions. Of
      great interest are the reactions of (*)NO(2) with oxymyoglobin and oxyhemoglobin,
      which are the predominant hemeproteins in biological systems. Although these
      reactions occur rapidly during the nitrite-catalyzed autoxidation of
      hemeproteins, their roles in systems producing (*)NO(2) in the presence of these
      hemeproteins have been greatly underestimated. In the present study, we employed
      pulse radiolysis to study directly the kinetics and mechanism of the reaction of
      oxymyoglobin (MbFe(II)O(2)) with (*)NO(2). The rate constant of this reaction was
      determined to be (4.5 +/- 0.3) x 10(7) M(-1)s(-1), and is among the highest rate
      constants measured for (*)NO(2) with any biomolecule at pH 7.4. The
      interconversion among the various oxidation states of myoglobin that is prompted
      by nitrogen oxide species is remarkable. The reaction of MbFe(II)O(2) with
      (*)NO(2) forms MbFe(III)OONO(2), which undergoes rapid heterolysis along the O-O
      bond to yield MbFe(V)=O and NO(3-). The perferryl-myoglobin (MbFe(V)=O)
      transforms rapidly into the ferryl species that has a radical site on the globin
      ((*)MbFe(IV)=O). The latter oxidizes another oxymyoglobin (10(4) M(-1)s(-1) <
      k(17) < 10(7) M(-1)s(-1)) and generates equal amounts of ferrylmyoglobin and
      metmyoglobin. At much longer times, the ferrylmyoglobin disappears through a
      relatively slow comproportionation with oxymyoglobin (k(18) = 21.3 +/- 5.3 M(
      1)s(-1)). Eventually, each (*)NO(2) radical converts three oxymyoglobin molecules
      into metmyoglobin. The same intermediate, namely MbFe(III)OONO(2), is also formed
      via the reaction peroxynitrate (O(2)NOO(-)/O(2)NOOH) with metmyoglobin (k(19) =
      (4.6 +/- 0.3) x 10(4) M(-1)s(-1)). The reaction of (*)NO(2) with ferrylmyoglobin
      (k(20) = (1.2 +/- 0.2) x 10(7) M(-1)s(-1)) yields MbFe(III)ONO(2), which in turn
      dissociates (k(21) = 190 +/- 20 s(-1)) into metmyoglobin and NO(3-). This rate
      constant was found to be the same as that measured for the decay of the
      intermediate formed in the reaction of MbFe(II)O(2) with (*)NO, which suggests
      that MbFe(III)ONO(2) is the intermediate observed in both processes. This
      conclusion is supported by thermokinetic arguments. The present results suggest
      that hemeproteins may detoxify (*)NO(2) and thus preempt deleterious processes,
      such as nitration of proteins. Such a possibility is substantiated by the
      observation that the reactions of (*)NO(2) with the various oxidation states of
      myoglobin lead to the formation of metmyoglobin, which, though not functional in
      the gas transport, is nevertheless nontoxic at physiological pH.

PMID- 15571392
TI  - Dynamics of hemoglobin in human erythrocytes and in solution: influence of
      viscosity studied by ultrafast vibrational echo experiments.
AB  - Ultrafast spectrally resolved stimulated vibrational echo experiments are used to
      measure the vibrational dephasing of the CO stretching mode of hemoglobin-CO
      (HbCO) inside living human erythrocytes (red blood cells), in liquid solutions,
      and in a glassy matrix. A method is presented to overcome the adverse impact on
      the vibrational echo signal from the strong light scattering caused by the cells.
      The results from the cytoplasmic HbCO are compared to experiments on aqueous HbCO
      samples prepared in different buffers, solutions containing low and high
      concentrations of glycerol, and in a solid trehalose matrix. Measurements are
      also presented that provide an accurate determination of the viscosity at the
      very high Hb concentration that is found inside the cells. It is demonstrated
      that the dynamics of the protein, as sensed by the CO ligand, are the same inside
      the erythrocytes and in aqueous solution and are independent of the viscosity. In
      solutions that are predominantly glycerol, the dynamics are modified somewhat but
      are still independent of viscosity. The experiments in trehalose give the
      dynamics at infinite viscosity and are used to separate the viscosity-dependent
      dynamics from the viscosity-independent dynamics. Although the HbCO dynamics are
      the same in the red blood cell and in the equivalent aqueous solutions,
      differences in the absorption spectra show that the distribution of a protein's
      equilibrium substates is sensitive to small pH differences.

PMID- 15571393
TI  - Loop-contraction mutagenesis of type 1 copper sites.
AB  - The shortest known type 1 copper binding loop (that of amicyanin, Ami) has been
      introduced into three different cupredoxin beta-barrel scaffolds. All of the loop
      contraction variants possess copper centers with authentic type 1 properties and
      are redox active. The Cu(II) and Co(II) sites experience only small structural
      alterations upon loop contraction with the largest changes in the azurin variant
      (AzAmi), which can be ascribed to the removal of a hydrogen bond to the
      coordinating thiolate sulfur of the Cys ligand. In all cases, loop contraction
      leads to an increase in the pK(a) of the His ligand found on the loop in the
      reduced proteins, and in the pseudoazurin (Paz) and plastocyanin (Pc) variants
      the values are almost identical to that of Ami ( approximately 6.7). Thus, in
      Paz, Pc, and Ami, the length of this loop tunes the pK(a) of the His ligand. In
      the AzAmi variant, the pK(a) is 5.5, which is considerably higher than the
      estimated value for Az (<2), and other controlling factors, along with loop
      length, are involved. The reduction potentials of the loop-contraction variants
      are all lower than those of the wild-type proteins by approximately 30-60 mV, and
      thus this property of a type 1 copper site is fine-tuned by the C-terminal loop.
      The electron self-exchange rate constant of Paz is significantly diminished by
      the introduction of a shorter loop. However, in PcAmi only a 2-fold decrease is
      observed and in AzAmi there is no effect, and thus in these two cupredoxins loop
      contraction does not significantly influence electron-transfer reactivity. Loop
      contraction provides an active site environment in all of the cupredoxins which
      is preferable for Cu(II), whereas previous loop elongation experiments always
      favored the cuprous site. Thus, the ligand-containing loop plays an important
      role in tuning the entatic nature of a type 1 copper center.

PMID- 15571394
TI  - Promoting vibrations in human purine nucleoside phosphorylase. A molecular
      dynamics and hybrid quantum mechanical/molecular mechanical study.
AB  - Crystallographic studies of human purine nucleoside phosphorylase (hPNP) with
      several transition-state (TS) analogues in the immucillin family showed an
      unusual geometric arrangement of the atoms O-5', O-4', and O(P), the nucleophilic
      phosphate oxygen, lying in a close three-oxygen stack. These observations were
      corroborated by extensive experimental kinetic isotope effect analysis. We
      propose that protein-facilitated dynamic modes in hPNP cause this stack, centered
      on the ribosyl O-4' oxygen, to squeeze together and push electrons toward the
      purine ring, stabilizing the oxacarbenium character of the TS. As the N-ribosidic
      bond is cleaved during the reaction, the pK(a) values of N-7 and O-6 increase by
      the electron density expelled by the oxygen-stack compression toward the purine
      ring. Increased electron density in the purine ring improves electrostatic
      interactions with nearby residues and facilitates the abstraction of a proton
      from a solvent proton or an unidentified general acid, making the purine a better
      leaving group, and accelerating catalysis. Classical and mixed quantum/classical
      molecular dynamics (MD) simulations of the Michaelis complex of hPNP with the
      substrates guanosine and phosphate were performed to assess the existence of
      protein-promoting vibrations (PPVs). Analogous simulations were performed for the
      substrates in aqueous solution. In the catalytic site, the O-5', O-4', and O(P)
      oxygens vibrate at frequencies of ca. 125 and 465 cm(-1), as opposed to 285 cm(
      1) in the absence of hPNP. The hybrid quantum mechanical/molecular mechanical
      method was used to assess whether this enzymatic vibration pushing the oxygens
      together is coupled to the reaction coordinate, and thus has a direct positive
      impact on catalysis. The potential energy surface for the phosphorolysis reaction
      for several snapshots taken from the classical MD simulation showed substantial
      differences in oxygen compression. Our calculations showed the existence of PPVs
      coupled to the reaction coordinate, which effect electronic alterations in the
      active site by pushing the three oxygen centers together in proximity, and
      accelerate substrate turnover in the phosphorolysis reaction catalyzed by hPNP.

PMID- 15571395
TI  - A proficient enzyme: insights on the mechanism of orotidine monophosphate
      decarboxylase from computer simulations.
AB  - Decarboxylation of orotidine 5'-monophosphate (Omp) to uridine 5'-monophosphate
      by orotidine 5'-monophosphate decarboxylase (ODCase) is currently the object of
      vivid debate. Here, we clarify its enzymatic activity with long time scale
      classical molecular dynamics and hybrid ab initio Car-Parrinello/molecular
      mechanics simulations. The lack of structural (experimental) information on the
      ground state of ODCase/Omp complex is overcome by a careful construction of the
      model and the analysis of three different strains of the enzyme. We find that the
      ODCase/substrate complex is characterized by a very stable charged network Omp
      Lys-Asp-Lys-Asp, which is incompatible with the previously proposed direct
      decarboxylation driven by a ground-state destabilization. A direct
      decarboxylation induced by a transition-state electrostatic stabilization is
      consistent with our findings. The calculated activation free energy for the
      direct decarboxylation with the formation of a C6 carboanionic intermediate
      yields an overall rate enhancement by the enzyme (k(cat)/k(wat) = 3.5 x 10(16))
      in agreement with experiments (k(cat)/k(wat) = 1.7 x 10(17)). The decarboxylation
      is accompanied by the movement of a fully conserved lysine residue toward the
      developing negative charge at the C6 position.

PMID- 15571396
TI  - Probing the hydrophobic cavity of lipid transfer protein from Nicotiana tabacum
      through xenon-based NMR spectroscopy.
AB  - The hydrophobic cavity of Lipid Transfer Protein 1 from Nicotiana tabacum is
      investigated in detail by NMR using xenon as a spy. The analysis of the (129)Xe
      chemical shifts and self-relaxation times gives evidence of protein-xenon
      interaction. Thermodynamics of the binding is characterized through the study of
      aliphatic (1)H and (13)C chemical shift variation as a function of xenon
      pressure. The binding constant is evaluated to 75.5 +/- 1.0 M(-1) at 293 K. The
      location of xenon inside the cavity is deduced from SPINOE experiments. The noble
      gas appears to occupy four sites, and xenon self-relaxation experiments indicate
      that it quickly jumps between different sites. The chemical shifts of amide
      protons and nitrogens also depend on the xenon concentration, either specifically
      or nonspecifically for atoms at the external surface of the protein. Yet,
      contrary to aliphatic atoms, they do not correspond to short-range interactions
      as confirmed by magnetization transfer experiments between laser-polarized xenon
      and protons in H(2)O. These (15)N chemical shift variations, used in combination
      with (15)N transverse self-relaxation rates to determine the lower limit of the
      binding rate, consequently reveal subtle changes in the structure of the protein
      upon binding.

PMID- 15571397
TI  - Synthetic ion channel activity documented by electrophysiological methods in
      living cells.
AB  - Hydraphiles are synthetic ion channels that use crown ethers as entry portals and
      that span phospholipid bilayer membranes. Proton and sodium cation transport by
      these compounds has been demonstrated in liposomes and planar bilayers. In the
      present work, whole cell patch clamp experiments show that hydraphiles integrate
      into the membranes of human embryonic kidney (HEK 293) cells and significantly
      increase membrane conductance. The altered membrane permeability is reversible,
      and the cells under study remain vital during the experiment. Control compounds
      that are too short (C(8)-benzyl channel) to span the bilayer or are inactive
      owing to a deficiency in the central relay do not induce similar conductance
      increases. Control experiments confirm that the inactive channel analogues do not
      show nonspecific effects such as activation of native channels. These studies
      show that the combination of structural features that have been designed into the
      hydraphiles afford true, albeit simple, channel function in live cells.

PMID- 15571398
TI  - Assembly of well-aligned multiwalled carbon nanotubes in confined
      polyacrylonitrile environments: electrospun composite nanofiber sheets.
AB  - Highly oriented, large area continuous composite nanofiber sheets made from
      surface-oxidized multiwalled carbon nanotubes (MWNTs) and polyacrylonitrile (PAN)
      were successfully developed using electrospinning. The preferred orientation of
      surface-oxidized MWNTs along the fiber axis was determined with transmission
      electron microscopy and electron diffraction. The surface morphology and height
      profile of the composite nanofibers were also investigated using an atomic force
      microscope in tapping mode. For the first time, it was observed that the
      orientation of the carbon nanotubes within the nanofibers was much higher than
      that of the PAN polymer crystal matrix as detected by two-dimensional wide-angle
      X-ray diffraction experiments. This suggests that not only surface tension and
      jet elongation but also the slow relaxation of the carbon nanotubes in the
      nanofibers are determining factors in the orientation of carbon nanotubes. The
      extensive fine absorption structure detected via UV/vis spectroscopy indicated
      that charge-transfer complexes formed between the surface-oxidized nanotubes and
      negatively charged (-CN[triple bond]N:) functional groups in PAN during
      electrospinning, leading to a strong interfacial bonding between the nanotubes
      and surrounding polymer chains. As a result of the highly anisotropic orientation
      and the formation of complexes, the composite nanofiber sheets possessed enhanced
      electrical conductivity, mechanical properties, thermal deformation temperature,
      thermal stability, and dimensional stability. The electrical conductivity of the
      PAN/MWNT composite nanofibers containing 20 wt % nanotubes was enhanced to
      approximately 1 S/cm. The tensile modulus values of the compressed composite
      nanofiber sheets were improved significantly to 10.9 and 14.5 GPa along the fiber
      winding direction at the MWNT loading of 10 and 20 wt %, respectively. The
      thermal deformation temperature increased with increased MWNT loading. The
      thermal expansion coefficient of the composite nanofiber sheets was also reduced
      by more than an order of magnitude to 13 x 10(-6)/ degrees C along the axis of
      aligned nanofibers containing 20 wt % MWNTs.

PMID- 15571399
TI  - Control of peptide structure and recognition by Fe(III)-induced helix
      destabilization.
AB  - Helical peptide segments that change their conformation due to external stimuli
      have often been employed in peptide-based molecular devices and materials. Using
      helices containing a pair of the iminodiacetic acid derivatives of lysine (Ida),
      we show that metal-induced helix destabilization is a promising approach to
      functional switching, especially for helices that are intrinsically stable. By i
      and i + 2 positioning of the Ida residues in a 17-residue model peptide, a
      significant decrease in the helical content was observed by the addition of
      Fe(III), whereas Fe(II) had no influence on the stability of the helix. The
      possibility of redox control of the helical structure was exemplified by the
      reduction of Fe(III) to Fe(II) using Na(2)S(2)O(4) followed by the subsequent
      reoxidation. Mutual recognition of the transcription factor Jun-derived leucine
      zipper peptide segment with the Fos leucine-zipper segment containing Ida
      residues was also modulated in the presence of Fe(III).

PMID- 15571400
TI  - N-halosuccinimide/BF3-H2O, efficient electrophilic halogenating systems for
      aromatics.
AB  - N-Halosuccinimides (NXS, 1) are efficiently activated in trifluoromethanesulfonic
      acid and BF(3)-H(2)O, allowing the halogenations of deactivated aromatics.
      Because BF(3)-H(2)O is more economic, easy to prepare, nonoxidizing, and offers
      sufficiently high acidity (-H(0) approximately 12, only slightly lower than that
      of trifluoromethanesulfonic acid), an efficient new electrophilic reagent
      combination of NXS/BF(3)-H(2)O has been developed. DFT calculations at the
      B3LYP/6-311++G//B3LYP/6-31G level suggest that protonated N-halosuccinimides
      undergo further protosolvation at higher acidities to reactive superelectrophilic
      species capable either in the transfer of X(+) from the protonated forms of NXS
      to the aromatic substrate or in forming a highly reactive and solvated X(+) which
      would readily react with the aromatic substrates. Structural aspects of the BF(3)
      H(2)O complex have also been investigated.

PMID- 15571401
TI  - Hydration of pyridylketenes: formation of acid enol and dihydropyridine
      (eneaminone) transients.
AB  - 2-, 3-, and 4-Pyridylketenes 4 formed in water by photochemical Wolff
      rearrangements using flash photolysis undergo rapid hydration forming transient
      intermediates observed by UV spectroscopy. 3-Pyridylketene (3-4) formed the acid
      enol intermediate 3-10 which was converted to the acid 3-11, and phenylketene
      gave similar behavior. 4-Pyridylketene (4-4) reacted with a similar initial rate
      constant of 5.0 x 10(4) s(-1) for decay of an absorption at 275 nm, with
      concomitant formation of a strong absorption at 370 nm with the same rate
      constant. The intermediate absorbing at 370 nm decayed with a lifetime 2.4 x
      10(3) fold longer than that of the ketene, and is identified as 4
      (carboxymethylene)-1,4-dihydropyridine (4-13), resulting from conjugate 1,6
      addition of H(2)O to 4-4. 2-Pyridylketene (2-4) underwent hydration with a
      similar rate constant of 1.1 x 10(4) s(-1) forming a transient with a UV
      absorption with maxima at 310 and 380 nm that decayed with biexponetial kinetics,
      with rate constants slower than the rate of formation by factors of 5.2 and 110,
      respectively. These results are interpreted as indicating the presence of two
      species, namely Z- and E-2-(carboxymethylene)-1,2-dihydropyridines (2-13),
      resulting from conjugate 1,4-addition of H(2)O to 2-4. The identifications of the
      1,2- and 1,4-(carboxymethylene)dihydropyridines 2- and 4-13 were confirmed by
      comparison of their UV spectra with those of the corresponding N-methyl
      derivatives. The amination of 2-pyridylketene in CH(3)CN was reinvestigated, and
      spectroscopic evidence, computational studies, and preparation of the N-methyl
      analogue demonstrated formation of the 1,2-dihydropyridine Z-2-8f as the long
      lived intermediate.

PMID- 15571402
TI  - Hybridization of oligonucleotide-modified silver and gold nanoparticles in
      aqueous dispersions and on gold films.
AB  - Functionalization of silver and gold nanoparticles by 12mer-thiolated homo
      oligonucleotides, SA and ST (containing only adenine or thymine, respectively),
      and their hybridization and dehybridization in aqueous dispersions have been
      described. In addition, ST and SA were self-assembled onto gold films and
      hybridized with their complementary pairs, unlabeled or labeled by gold and
      silver nanoparticles. The base pairing between DNA strands and the types of
      oligonucleotides (adenine or thymine) attached to the nanoparticles was detected
      by Polarization Modulated Fourier Transform Infrared Reflection Absorption
      Spectroscopy (PM-FTIRRAS).

PMID- 15571403
TI  - Direct measurement of the hydrogen-bonding effect on the intrinsic redox
      potentials of [4Fe-4S] cubane complexes.
AB  - To probe how H-bonding effects the redox potential changes in Fe-S proteins, we
      produced and studied a series of gaseous cubane-type analogue complexes,
      [Fe(4)S(4)(SEt)(3)(SC(n)H(2n+1))](2-) and [Fe(4)S(4)(SEt)(3)(SC(n)H(2n)OH)](2-)
      (n = 4, 6, 11; Et = C(2)H(5)). Intrinsic redox potentials for the
      [Fe(4)S(4)](2+/3+) redox couple involved in these complexes were measured by
      photoelectron spectroscopy. The oxidation energies from
      [Fe(4)S(4)(SEt)(3)(SC(n)H(2n)OH)](2-) to [Fe(4)S(4)(SEt)(3)(SC(n)H(2n)OH)](-)
      were determined directly from the photoelectron spectra to be approximately 130
      meV higher than those for the corresponding [Fe(4)S(4)(SEt)(3)(SC(n)H(2n+1))](2-)
      systems, because of the OH...S hydrogen bond in the former. Preliminary Monte
      Carlo and density functional calculations showed that the H-bonding takes place
      between the -OH group and the S on the terminal ligand in
      [Fe(4)S(4)(SEt)(3)(SC(6)H(12)OH)](2-). The current data provide a direct
      experimental measure of a net H-bonding effect on the redox potential of
      [Fe(4)S(4)] clusters without the perturbation of other environmental effects.

PMID- 15571404
TI  - A new type of intermediate, C+(BCH3)11- <--> C(BCH3)11, in a Grob fragmentation
      coupled with intramolecular hydride transfer. A nonclassical carbocation ylide or
      a carbenoid?
AB  - In solvolysis of alkyl halides Hal-(CH(2))(n)-C(BCH(3))(11)(-) (n = 2, 5, 6, but
      not 3, 4, or 7) and protonation of alkenes CH(2)=CH-(CH(2))(n)(-)(2)
      C(BCH(3))(11)(-) (n = 3, 6, 7, but not 4 or 5) carrying the icosahedral
      electrofuge -C(BCH(3))(11)(-) attached through its cage carbon atom, generation
      of incipient positive charge on C(alpha) (as shown in Scheme 1 in the article)
      leads to simultaneous cleavage of the C(beta)-C(BCH(3))(11)(-) bond. The products
      are a C(alpha)=C(beta) alkene and a postulated intermediate C(+)(BCH(3))(11)(-) <
      -> C(BCH(3))(11), trapped as the adduct Nu-C(BCH(3))(11)(-) by one of the
      nucleophiles (Nu(-)) present. The reaction kinetics is E1, first order in the
      haloalkylcarborane and zero order in [Nu(-)], and the elimination appears to be
      concerted, as in the usual E2 mechanism. The process is best viewed as a Grob
      fragmentation. The loss of the longer chains involves intrachain hydride transfer
      from the C(alpha)-H bond to an incipient carbocation on C(delta)(') or
      C(epsilon)(') via a five- or six-membered cyclic transition state, respectively.
      The electronic structure of the postulated intermediate is believed to lie
      between those of a nonclassical carbonium ylide C(+)(BCH(3))(11)(-) and a
      carbenoid C(BCH(3))(11) whose electronic ground state resembles the S(2) state of
      ordinary carbenes.

PMID- 15571405
TI  - Linear rheology of water-soluble reversible neodymium(III) coordination polymers.
AB  - The rheology of reversible coordination polymer networks in aqueous solution is
      studied. The polymers are formed by neodymium(III) ions and bifunctional ligands,
      consisting of two pyridine-2,6-dicarboxylate groups connected at the 4-positions
      by an ethylene oxide spacer. Neodymium(III) ions can bind three of these
      terdendate ligand groups. At high concentrations, the polymer networks yield
      viscoelastic materials, which can be described with the Maxwell model. The
      scaling of the elastic modulus, relaxation time, and zero-shear viscosity with
      concentration are in good agreement with the predictions of Cates' model that
      describes the dynamics of linear equilibrium polymers. This indicates that the
      networks have only few cross-links and can be described as linear equilibrium
      polymers. The gels are also thermo-reversible. At high temperatures, fast
      relaxation was found, resulting in liquidlike behavior. Upon cooling, the
      viscoelastic properties returned immediately. From the temperature dependence of
      the relaxation time, an activation energy of 49 kJ/mol was determined for the
      breaking and reptation of the polymers.

PMID- 15571406
TI  - Difference rule-a new thermodynamic principle: prediction of standard
      thermodynamic data for inorganic solvates.
AB  - We present a quite general thermodynamic "difference" rule, derived from
      thermochemical first principles, quantifying the difference between the standard
      thermodynamic properties, P, of a solid n-solvate (or n-hydrate), n-S, containing
      n molecules of solvate, S (water or other) and the corresponding solid parent
      (unsolvated) salt: [P[n-solvate] - P[parent]]/n = constant = theta(P)[S,s-s], or
      n-S and other solvate, n'-S: [P[-solvate] - P[n'-solvate]]/(n - n') = [P[n-S ] -
      P[n'-S]]/(n - n') = constant = theta(P)[S,s-s] where P may be any one of: U(POT)
      (the lattice potential energy), V(m) (the molecular or formula unit volume),
      Delta(f)H degrees , Delta(f)S degrees , Delta(f)G degrees or (the standard
      thermodynamic functions of formation and the absolute entropy), and n can be
      noninteger. The constants, theta(P)[S,s-s], for each property, P, of solvate of
      type S, are established by correlation of the available set of experimental data.
      We also show that, when solid-state data for a particular solvate is sparse,
      theta(P)[S,s-s] can be reliably predicted from liquid-state values, P[S,l], or
      even gas-state values, P[S,g]. This rule offers a powerful means for predicting
      unknown thermodynamic data, extending the compass of currently known
      thermodynamic information. Systems considered involve the following solvates:
      H(2)O (hydrates), D(2)O, NH(3), ND(3), (CH(3))(2)O, NaOH, CH(3)OH, C(2)H(5)OH,
      (CH(2)OH)(2), H(2)S, SO(2), HF, KOH, and (CH(CH(3))(2))(2)O. Detailed examples of
      usage are given for hydrates and for SO(2).

PMID- 15571407
TI  - Synthetic, structural, and mechanistic aspects of an amine activation process
      mediated at a zwitterionic Pd(II) center.
AB  - A zwitterionic palladium complex [[Ph(2)BP(2)]Pd(THF)(2)][OTf] (1) (where
      [Ph(2)BP(2)] = [Ph(2)B(CH(2)PPh(2))(2)](-)) reacts with trialkylamines to
      activate a C-H bond adjacent to the amine N atom, thereby producing iminium
      adduct complexes [Ph(2)BP(2)]Pd(N,C:eta(2)-NR(2)CHR'). In all cases examined the
      amine activation process is selective for the secondary C-H bond position
      adjacent to the N atom. These palladacycles undergo facile beta-hydride
      elimination/olefin reinsertion processes as evident from deuterium scrambling
      studies and chemical trap studies. The kinetics of the amine activation process
      was explored, and beta-hydride elimination appears to be the rate-limiting step.
      A large kinetic deuterium isotope effect for the amine activation process is
      evident. The reaction profile in less polar solvents such as benzene and toluene
      is different at room temperature and leads to dimeric [[Ph(2)BP(2)]Pd](2) (4) as
      the dominant palladium product. Low-temperature toluene-d(8) experiments proceed
      more cleanly, and intermediates assigned as [Ph(2)BP(2)]Pd(NEt(3))(OTf) and the
      iminium hydride species [[Ph(2)BP(2)]Pd(H)(Et(2)N=CHCH(3))][OTf] are directly
      observed. The complex (Ph(2)SiP(2))Pd(OTf)(2) (14) was also studied for amine
      activation and generates dimeric [(Ph(2)SiP(2))Pd](2)[OTf](2) (16) as the
      dominant palladium product. These collective data are discussed with respect to
      the mechanism of the amine activation and, in particular, the influence that
      solvent polarity and charge have on the overall reaction profile.

PMID- 15571408
TI  - Insignificance of P-H...P hydrogen bonding: structural chemistry of neutral and
      protonated 1,8-di(phosphinyl)naphthalene.
AB  - While there is extensive information on 1,8-di(amino)naphthalene (i.e., the
      parent compound of the "proton sponge" series), the corresponding phosphorus
      compound has not been described. A high-yield synthesis of 1,8
      di(phosphinyl)naphthalene (9) and the 1-naphthylphosphine reference compound (4)
      is now reported. Thermal decomposition of 9 leads to intramolecular
      dehydrogenative P-P coupling to afford 1,2-dihydro-1,2-diphosphaacenaphthene
      (10). Protonation of 9 and 4 with CF(3)SO(3)H gives quantitative yields of the
      monophosphonium salts 11 and 5, respectively. With excess acid and traces of
      moisture, the hydronium salt [C(10)H(6)(PH(2))(PH(3))](+)[H(3)O](+)2[CF(3)SO(3)](
      ) (13) is obtained. The structures of 9, 11, and 13 have been determined.
      Molecules of 9 have a planar naphthalene skeleton, C(10)H(6)P(2), with the two 
      PH(2) groups in a transoid conformation. The molecules form loose dimers in the
      crystal, the individual chiral enantiomers of which are related by a center of
      inversion. In contrast to the situation for the amino analogue, and despite the
      proximity of the two -PH(2) functions, there is no intra- or intermolecular
      hydrogen bonding. Solutions of 9 (in CD(2)Cl(2)) show equivalent P-bound hydrogen
      atoms due to conformational fluctionality. By analysis of the
      ABCD(2)XX'D'(2)C'B'A' spin system, it was shown that, in 9, there are strong
      through-space pericouplings [(n)J(P(X)P(X)(')) = 221.6 Hz, (n)J(P(X)H(D)(')) =
      31.7 Hz, (n)J(H(D)H(D)(')) = 3.9 Hz]. In the cations of 11, the C(10)H(6)P(2)
      skeleton is also planar (by C(s) symmetry), with the -PH(2) and -PH(3)(+) groups
      in a conformation which rules out any P-H...P hydrogen bonding. The hydronium
      cation and the two triflate anions in 13 are associated into an anionic network
      through extensive hydrogen bonding surrounding stacks of the phosphonium cations.
      In solution, the cations of 11 and 13 show separate (31)P resonances for the two
      phosphorus atoms with fully resolved (1)J(PH) couplings, which indicate that
      there is no intra- or intercationic proton exchange. By contrast, the NMR spectra
      of solutions of [C(10)H(6)(NH(2))(NH(3))](+)X(-) salts show proton scrambling
      equilibrating all five N-bound hydrogen atoms, and in the crystal, the
      conformations of the cations feature intramolecular N-H...N hydrogen bonding.

PMID- 15571409
TI  - Dynamic and redox active pillared bilayer open framework: single-crystal-to
      single-crystal transformations upon guest removal, guest exchange, and framework
      oxidation.
AB  - A metal-organic pillared bilayer open framework having 3D channels,
      [Ni(2)(C(26)H(52)N(10))](3)[BTC](4).6C(5)H(5)N.36H(2)O (BOF-1, 1), has been
      assembled from bismacrocyclic nickel(II) complex
      [Ni(2)(C(26)H(52)N(10))(Cl)(4)].H(2)O and sodium 1,3,5-benzenetricarboxylate
      (Na(3)BTC). The channels are occupied by pyridine and water guest molecules. When
      the single crystal of 1 was dried in air and then heated at 75 degrees C for 1.5
      h, respectively, [Ni(2)(C(26)H(52)N(10))](3)[BTC](4).30H(2)O (1') and
      [Ni(2)(C(26)H(52)N(10))](3)[BTC](4).4H(2)O (2) resulted with retention of the
      single crystallinity. The X-ray structures reveal spongelike dynamic behavior of
      the bilayer framework that reduces the interlayer distance in response to the
      amount of guest molecules. Solid 2 differentiates various alcohols. When 1 was
      immersed in pyridine and benzene, guest molecules were exchanged with retention
      of the single-crystal nature to give rise to
      [Ni(2)(C(26)H(52)N(10))](3)[BTC](4).20pyridine.6H(2)O (3) and
      [Ni(2)(C(26)H(52)N(10))](3)[BTC](4).14benzene.19H(2)O (4), respectively.
      Furthermore, crystal 1 reacted with I(2) via single-crystal-to-single-crystal
      transformation to produce
      [Ni(2)(C(26)H(52)N(10))](3)[C(9)H(3)O(6)](4)(I(3))(4).nI(2).17H(2)O (5) that
      consists of positively charged framework incorporating nickel(III) and nickel(II)
      ions and the channels including I(3)(-) and I(2).

PMID- 15571410
TI  - Self-assembly and molecular recognition of a luminescent gold rectangle.
AB  - A luminescent molecular rectangle [Au(4)(micro-PAnP)(2)(micro-bipy)(2)](OTf)(4)
      (1.(OTf)(4)) (PAnP = 9,10-bis(diphenylphosphino)anthracene, bipy = 4,4'
      bipyridine, X = NO(3)(-) or OTf(-)), synthesized from the self-assembly of the
      molecular "clip" Au(2)(micro-PAnP)(OTf)(2) and bipy, shows a large rectangular
      cavity of 7.921(3) x 16.76(3) A. The electronic absorption and emission
      spectroscopy, and electrochemistry of the metallacyclophane, have been studied.
      The 1(4+) ions are self-assembled into 2D mosaic in the solid state via
      complementary edge-to-face interactions between the Ph groups. (1)H NMR
      titrations ratify the 1:1 complexation between 1(4+) and various aromatic
      molecules. Comparing the structures of the inclusion complexes indicates an
      induced-fit mechanism operating in the binding. The emission of 1(4+) is quenched
      upon the guest binding. The binding constants are determined by both (1)H NMR and
      fluorescence titrations. Solvophobic and ion-dipole effects are shown to be
      important in stabilizing the inclusion complexes.

PMID- 15571411
TI  - Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene
      derivatives.
AB  - Amphiphilic cationic polynorbornene derivatives, soluble in water, were prepared
      from modular norbornene monomers, with a wide range of molecular weights (M(n) =
      1600-137 500 g/mol) and narrow polydispersities (PDI = 1.1-1.3). The
      antibacterial activity determined by growth inhibition assays and the hemolytic
      activity against human red blood cells were measured and compared to determine
      the selectivity of the polymers for bacterial over mammalian cells. The effects
      of monomer repeat unit hydrophobicity and polymer molecular weight on
      antibacterial and hemolytic activities were determined. The hydrophobicity of the
      repeat unit was observed to have dramatic effects on antibacterial and hemolytic
      activities. Lipid membrane disruption activities of the polymers was confirmed by
      measuring polymer-induced dye leakage from large unilamellar vesicles. By tuning
      the overall hydrophobicity of the polymer through random copolymerizations of
      modular norbornene derivatives, highly selective, nonhemolytic antibacterial
      activities were obtained. For appropriate monomer composition, selectivity
      against bacteria versus human red blood cells was determined to be over 100.

PMID- 15571412
TI  - Nitrile-functionalized pyridinium ionic liquids: synthesis, characterization, and
      their application in carbon-carbon coupling reactions.
AB  - A series of relatively low-cost ionic liquids, based on the N-butyronitrile
      pyridinium cation [C(3)CNpy](+), designed to improve catalyst retention, have
      been prepared and evaluated in Suzuki and Stille coupling reactions. Depending on
      the nature of the anion, these salts react with palladium chloride to form
      [C(3)CNpy](2)[PdCl(4)] when the anion is Cl(-) and complexes of the formula
      [PdCl(2)(C(3)CNpy)(2)][anion](2) when the anion is PF(6)(-), BF(4)(-), or
      N(SO(2)CF(3))(2)(-). The solid-state structures of [C(3)CNpy]Cl and
      [C(3)CNpy](2)[PdCl(4)] have been established by single-crystal X-ray diffraction.
      The catalytic activity of these palladium complexes following immobilization in
      both N-butylpyridinium and nitrile-functionalized ionic liquids has been
      evaluated in Suzuki and Stille coupling reactions. All of the palladium complexes
      show good catalytic activity, but recycling and reuse is considerably superior in
      the nitrile-functionalized ionic liquid. Inductive coupled plasma spectroscopy
      reveals that the presence of the coordinating nitrile moiety in the ionic liquid
      leads to a significant decrease in palladium leaching relative to simple N
      alkylpyridinium ionic liquids. Palladium nanoparticles have been identified as
      the active catalyst in the Stille reaction and were characterized using
      transmission electron microscopy.

PMID- 15571413
TI  - Contiguous versus segmented hydrophobicity in micellar systems.
AB  - This paper addresses a question not yet posed systematically in surfactant
      chemistry: How do the colloidal properties of surfactants respond to insertion of
      non-hydrocarbon functionalities (i.e., ester groups) within chains that are
      normally entirely hydrocarbon? In answering this question, two classes of such
      chain-modified surfactants were discovered. One class forms only small aggregates
      with noncooperative self-assembly, low foaming, high areas of occupancy at the
      air/water interface, and weak solid-adsorption and solubilization properties. The
      other class is much more normal with regard to these properties and, in fact, can
      even exceed conventional surfactants in mesitylene solubilization. Differences
      between the two categories of chain-modified surfactants originate from the
      degree of segmentation of the hydrocarbon and, in particular, upon the location
      of the longest segment. Segmented hydrophobicity, having in principle a
      "hydrophobic potential" similar to that of a contiguous hydrophobicity of equal
      length, can induce aggregation but, concurrently, alters the mode of assembly
      into films and micelles.

PMID- 15571414
TI  - Surface reaction of alkynes and alkenes with H-Si(111): a density functional
      theory study.
AB  - Recent experiments on the addition of alkene and alkyne molecules to H-terminated
      silicon surfaces have provided evidence for a surface chain reaction initiated at
      isolated Si dangling bonds and involving an intermediate carbon radical state,
      which, after abstraction of a hydrogen atom from a neighboring Si-H unit,
      transforms into a stable adsorbed species plus a new Si dangling bond. Using
      periodic density functional theory (DFT) calculations, together with an efficient
      method for determining reaction pathways, we have studied the initial steps of
      this chain reaction for a few different terminal alkynes and alkenes interacting
      with an isolated Si dangling bond on an otherwise H-saturated Si(111) surface.
      Calculated minimum energy pathways (MEPs) indicate that the chain mechanism is
      viable in the case of C(2)H(2), whereas for C(2)H(4) the stabilization of the
      intermediate state is so small and the barrier for H-abstraction so (relatively)
      large that the molecule is more likely to desorb than to form a stable adsorbed
      species. For phenylacetylene and styrene, stabilization of the intermediate state
      and decrease of the H-abstraction barrier take place. While a stable adsorbed
      species exists in both cases, the overall heat of adsorption is larger for the
      alkyne molecules.

PMID- 15571415
TI  - Molecular conductance: chemical trends of anchoring groups.
AB  - Combining density functional theory calculations for molecular electronic
      structure with a Green function method for electron transport, we calculate from
      first principles the molecular conductance of benzene connected to two Au leads
      through different anchoring atoms-S, Se, and Te. The relaxed atomic structure of
      the contact, different lead orientations, and different adsorption sites are
      fully considered. We find that the molecule-lead coupling, electron transfer, and
      conductance all depend strongly on the adsorption site, lead orientation, and
      local contact atomic configuration. For flat contacts the conductance decreases
      as the atomic number of the anchoring atom increases, regardless of the
      adsorption site, lead orientation, or bias. For small bias this chemical trend
      is, however, dependent on the contact atomic configuration: an additional Au atom
      at the contact with the (111) lead changes the best anchoring atom from S to Se,
      although for large bias the original chemical trend is recovered.

PMID- 15571416
TI  - Structure and dynamics of a molecular hydrogel derived from a tripodal cholamide.
AB  - Tripodal cholamide 1 is a supergelator of aqueous fluids. A variety of physical
      techniques, including cryo-transmission electron microscopy (TEM), circular
      dichroism (CD), steady-state fluorescence, time-resolved fluorescence, and
      dynamic light-scattering, were employed to understand the structure and dynamics
      of the gel. Fluorescent probes [ANS (8-anilinonaphthalene-1-sulfonic acid) and
      pyrene] reported two critical aggregation concentrations (CAC(1) and CAC(2)) of 1
      in predominantly aqueous media, with the minimum gel concentration (MGC) being
      close to CAC(2). Fluorescence lifetime measurements with pyrene revealed
      ineffective quenching of pyrene fluorescence by oxygen, possibly caused by slower
      Brownian diffusion due to the enhanced viscosity in the gel phase. The study of
      the gelation kinetics by monitoring the ultrafast dynamics of ANS revealed a
      progressive increase in the aggregate size and the microviscosity of the aqueous
      pool encompassed by the self-assembled fibrillar network (SAFIN) during the
      gelation. The striking difference between microviscosity and bulk (macroscopic)
      viscosity of the gel is also discussed.

PMID- 15571417
TI  - Consistent experimental and theoretical evidence for long-lived intermediate
      radicals in living free radical polymerization.
AB  - The cumyl dithiobenzoate (CDB)-mediated reversible addition fragmentation chain
      transfer (RAFT) polymerization of styrene at 30 degrees C is studied via both
      kinetic experiments and high-level ab initio molecular orbital calculations. The
      kinetic data clearly indicate the delayed onset of steady-state behavior. Such an
      observation is consistent with the slow fragmentation model for the RAFT process,
      but cannot be reconciled with the cross-termination model. The comprehensive
      failure of the cross-termination model is quantitatively demonstrated in a
      detailed kinetic analysis, in which the independent influences of the pre
      equilibria and main equilibria and the possible chain length dependence of cross
      termination are fully taken into account. In contrast, the slow fragmentation
      model can describe the data, provided the main equilibrium has a large
      fragmentation constant of at least 8.9 x 10(6) L mol(-1). Such a high equilibrium
      constant (for both equilibria) is consistent with high-level ab initio quantum
      chemical calculations (K = 7.3 x 10(6) L mol(-1)) and thus appears to be
      physically realistic. Given that the addition rate coefficient for macroradicals
      to (polymeric) RAFT agent is 4 x 10(6) L mol(-1) s(-1), this implies that the
      lifetime of the RAFT adduct radicals is close to 2.5 s. Since the radical is also
      kinetically stable to termination, it can thus function as a radical sink in its
      own right.

PMID- 15571420
TI  - Aptamers in research and drug development.
AB  - Aptamers are short single-stranded oligonucleotides that fold into well defined
      three-dimensional shapes allowing them to bind to and inhibit their targets with
      high affinity and specificity. Aptamers can be considered truly multifunctional
      tools, because they can be generated rapidly and applied for specific detection,
      inhibition, and characterization of proteins. Recent publications impressively
      confirm that aptamers can be used either as surrogate inhibitors for the
      identification of small molecule lead compounds or as biopharmaceuticals.

PMID- 15571421
TI  - Cellular vehicles for cancer gene therapy: current status and future potential.
AB  - Cancer is a difficult target for any therapeutic strategy; therefore, there is a
      continuous search for new therapeutic modalities, for application either alone or
      in combination. In this regard, gene-based therapy is a new approach that offers
      hope of improved control of tumors. Intensive research to apply gene therapy for
      cancer treatment has led to identification of the most important technical and
      theoretical barriers that need to be overcome for clinical success. One of the
      central unresolved challenges remains the issue of specific and efficient
      delivery of genes to target cells or tissues, emphasizing the importance of the
      gene carrier. Along with different viral and non-viral vector systems, mammalian
      cells have also been considered as vehicles for delivery of anti-cancer
      therapeutics. The cell-based delivery approach was introduced as the first
      attempt to apply gene therapy to cancer treatment, and in general, has followed
      most of the ups and downs of gene therapy applications, progressing alongside new
      knowledge gained in this field. As a result, significant progress has been made
      in some aspects of the cell-based approach, while the development of other
      essential issues is only just gaining speed. It appears that the initial phase of
      development of cell-based protocols - the achievement of efficient ex vivo cell
      loading with therapeutics - has largely been fulfilled. However, the desired
      efficacy of cell-based strategies in general has not yet been reached, and
      specificity of tumor homing needs to be improved considerably. There is hope that
      advances in related scientific fields will promote the utilization of cells as
      powerful and versatile vehicles for cancer gene therapy.

PMID- 15571422
TI  - Recent trends and advances in immunodiagnostics of solid tumors.
AB  - The development of new cancer immunodiagnostic tests measuring soluble markers
      can be divided along the lines of single analyte measurement versus multiplex
      analysis. In the measurement of single analytes, newly proposed test analytes
      still struggle with the same issues as their predecessors; namely, can the
      measurement of a single biomarker be sufficiently sensitive and specific for
      screening the general population? Probably the best example of this challenge is
      in the area of bladder cancer detection, where several newly identified markers
      are being clinically evaluated in multicenter trials. In order to surmount this
      hurdle, multiplex analysis has become an increasingly important research focus.
      By combining the statistical power of measuring many cancer-associated analytes,
      it is hoped that highly specific diagnostic tests can be developed that are
      suitable for screening the general population. Some of the most impressive data
      for multiplex cancer biomarker detection derive from a non-immunologic technique 
      mass spectroscopy. Multiplex analysis has also recently been applied to the
      measurement of serum antibodies to tumor-associated antigens. Recent data link
      the development of antibodies to tumor-associated antigens with the presence of
      solid tumors. This strategy is a departure from the more traditional assay format
      of measuring the antigens themselves, and is another promising emerging area of
      investigation for the early detection of solid tumors. Solid tumor analysis by
      quantitative immunohistochemical staining is another rapidly growing area of
      cancer immunodiagnosis. This field has become especially important in the context
      of pharmacodiagnostics - the coupling of cancer therapy to the outcome of a test
      measurement from a patient biopsy. Standardization and assay reproducibility
      appear to be the most significant challenges in this context. In summary,
      developments over the past several years give reason for excitement and optimism
      about the potential for cancer immunodiagnostics to meaningfully impact cancer
      patient survival. In this review we take a fresh look at the field of cancer
      immunodiagnostics, to identify these recent and emerging trends that may impact
      on clinical practice over the next few years.

PMID- 15571423
TI  - Regulation of biogenerics: a survey of viewpoints.
AB  - BACKGROUND AND OBJECTIVES: 'Biogenerics' regulation has brought about a heated
      debate within the EU as the first biopharmaceuticals are going off patent. This
      study aims to examine the opportunities and challenges offered by biogenerics by
      surveying the viewpoints of experts in regulatory agencies and in companies
      developing novel biopharmaceuticals and biogenerics. METHODS: Oral interviews
      were conducted in 2002 and 2003 with experts including representatives of the
      European Generic Medicines Association (EGA) and the European Federation of
      Pharmaceutical Industries and Associations (EFPIA) in Brussels, three innovator
      biotech companies, and five other experts in Finland. Additionally, four
      biogenerics companies and one innovator company abroad answered a structured,
      written questionnaire. RESULTS AND CONCLUSION: According to this study,
      biogenerics should be regulated on a case-by-case basis. The interviewees were
      not unanimous as to whether comparability can be addressed and which are the most
      challenging areas for proving comparability. Immunogenicity was considered to be
      a major problem for biogenerics. Therefore, a requirement for an intensified
      monitoring of the safety profile during post-marketing was thought to be
      justified in many cases.

PMID- 15571424
TI  - Interleukin-2 plus ribavirin versus interferon-alpha-2b plus ribavirin in
      patients with chronic hepatitis C who did not respond to previous interferon
      alpha-2b treatment.
AB  - BACKGROUND: Interferon (IFN)-alpha-2b therapy has been shown to improve clinical
      conditions of patients with chronic hepatitis C. Several studies showed that the
      addition of ribavirin to IFNalpha-2b greatly improved the biochemical as well as
      the virologic and histological response rate in patients with chronic hepatitis
      C. The aim of this study was to evaluate biochemical, virologic, and histological
      responses as well as adherence to a treatment employing ribavirin plus low doses
      of recombinant interleukin (IL-2) or IFNalpha-2b in subjects with chronic active
      hepatitis C, which relapsed or did not respond to previous treatment with
      interferon alone. PATIENTS AND METHODS: We evaluated all 75 consecutive adult
      patients with chronic hepatitis C admitted to our department, who were previously
      treated with one course of recombinant or lymphoblastoid IFNalpha-2b (3 million
      to 6 million IU three times a week for at least 4 months), and either relapsed or
      did not respond to this treatment. Sixty patients met the inclusion criteria for
      enrollment in our study. Randomization was performed on the basis of a computer
      generated list. The treatment schedule was based on subcutaneous administration
      of recombinant IFNalpha-2b (Intron A) at a dosage of 3 million IU every day, or
      IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin
      administered 400 mg twice daily (morning and night) [for patients weighing <75
      kg] or 500 mg twice daily (for those weighing > or = 75 kg). The planned
      treatment period was 6 months. RESULTS: Both IFN and IL-2 treatment groups
      achieved a significant biochemical response with respect to baseline values at
      the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p
      < 0.001 for both). The differences between the two groups at the end of treatment
      and at the end of the follow up were significant (p < 0.04 and p < 0.003
      respectively) in favor of IL-2-treatment. The virologic response rate for IL-2
      treated patients was significantly higher than for IFN-treated patients at months
      3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant
      improvement in histological activity index with respect to baseline values, but
      the difference between the groups was not significant. No withdrawals have been
      registered. CONCLUSION: The combination of IL-2 and ribavirin seems to increase
      the probability of a sustained biochemical and virologic response in patients
      with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2
      plus ribavirin may provide a clinically important option that appears to be well
      tolerated and effective in patients with chronic hepatitis C virus infection.

PMID- 15571425
TI  - Spotlight on omalizumab in allergic asthma.
AB  - Omalizumab (Xolair) is a humanized monoclonal antibody used in the treatment of
      adolescent and adult patients with moderate to severe allergic asthma
      inadequately controlled with inhaled corticosteroids (ICS). It selectively binds
      to circulating immunoglobulin E (IgE) and, thereby, prevents binding of IgE to
      mast cells and other effector cells. Without surface-bound IgE, these cells are
      unable to recognize allergens, thus preventing cellular activation by antigens
      and the subsequent allergic/asthmatic symptoms. Omalizumab decreases free serum
      IgE levels in a dose-dependent manner, reduces IgE receptor density on effector
      cells, and significantly improves airway inflammation parameters. Omalizumab is
      slowly absorbed after subcutaneous administration, and mean elimination half-life
      is 26 days, thus allowing infrequent administration of the drug. Omalizumab
      dosage is determined by bodyweight and pretreatment serum total IgE levels.
      Patients treated with subcutaneous omalizumab in clinical trials received a
      dosage that was approximately equal to 0.016 mg/kg/IgE (IU/mL) per 4 weeks. Thus,
      patients received 150 or 300 mg every 4 weeks, or 225, 300, or 375 mg every 2
      weeks. In adults and adolescents (> or = 12 years of age) with moderate to severe
      allergic asthma, subcutaneous administration of omalizumab as add-on therapy with
      ICS improved the number of asthma exacerbations, rescue medication use, asthma
      symptom scores, and quality-of-life (QOL) scores compared with placebo during 28-
      and 32-week double-blind trials. In addition, concomitant ICS use was
      significantly decreased in patients receiving omalizumab, and in the two largest
      double-blind trials approximately 40% of omalizumab recipients completely
      withdrew from ICS therapy while maintaining effective asthma control. In general,
      results of extension studies showed that the beneficial effects of omalizumab
      were maintained over a total period of 52 weeks. Omalizumab was well tolerated as
      add-on therapy with ICS during treatment for up to 52 weeks. Common adverse
      events in clinical trials included injection site reaction, viral infection,
      upper respiratory tract infection, sinusitis, headache, and pharyngitis, although
      the incidence of adverse events with omalizumab was similar to that with placebo.
      In conclusion, omalizumab, as add-on therapy with ICS, is an effective and well
      tolerated agent for the treatment of moderate to severe allergic asthma in
      adolescents and adults. In addition to its symptomatic and QOL benefits,
      omalizumab therapy allows ICS dosage reduction or discontinuation of ICS in many
      patients. Comparisons of omalizumab with other asthma therapies have yet to be
      conducted; however, clinical efficacy and tolerability data indicate that
      omalizumab is a valuable option in the treatment of allergic asthma.

PMID- 15571426
TI  - Exercise programmes for patients with chronic heart failure.
AB  - The safety and efficacy of exercise training in patients with chronic heart
      failure (CHF) have been reported in a large number of scientific studies, with
      endurance training representing the most frequently applied training stimulus.
      Beneath the common continuous method of endurance training, the interval method
      (short bouts of intense exercise interspersed with pre-scheduled rest intervals),
      was also applied in some studies. Ergometric testing is a prerequisite for all
      individualised training prescription and is an appropriate method of efficacy
      documentation. However, there is a surprisingly large range of exercise
      intensities being prescribed to patients with CHF. Most of the prescription
      models refer to maximal ergometric measurements. Submaximal references from
      lactate and ventilatory curves represent an alternative method in measuring
      accuracy and efficacy of training. The course of heart rate during submaximal
      incremental exercise can be reliably used to indicate endurance gains in CHF.
      Some positive reports exist for carefully executed strength endurance training
      for patients with CHF and there are convincing arguments for the use of
      coordination and flexibility exercises; however, substantial scientific evidence
      is lacking.

PMID- 15571427
TI  - Lipid-induced insulin resistance in the liver: role of exercise.
AB  - Hepatic lipid accumulation may be a result of one or several of the following
      factors: increased delivery of adipose tissue or dietary fatty acids to the
      liver, increased de novo synthesis of fatty acids in the liver, decreased rate of
      hepatic fatty-acid oxidation, or decreased rate in the exit of fatty acids from
      the liver in the form of triglycerides. Delivery of fatty acids to the liver
      appears to be the most potent mechanism for hepatic lipid accumulation. Hepatic
      lipid accumulation is linked to the development of hepatic insulin resistance,
      which is demonstrated by the impaired suppression of hepatic glucose output by
      insulin. Current evidence suggests that defects associated with the molecular
      mechanisms responsible for the propagation of the insulin signal in the liver
      cells are responsible for the impaired insulin effect and that these defects can
      develop secondary to lipid accumulation in the liver. Hepatic lipid accumulation
      appears to affect the activity of phosphatidylinositol 3-kinase, which has a
      central role in mediating the insulin action in hepatocytes. Generally, exercise
      has been shown to enhance the insulin action in the liver. Although an exercise
      related mechanistic link between attenuation in hepatic lipid accumulation and
      enhancement in insulin action in the liver has not been described yet, the
      benefits of exercise on hepatic insulin action may relate to the potential
      effects of exercise on regulating/preventing hepatic lipid accumulation. However,
      direct effects of exercise on insulin action in the liver, independent of any
      effects on hepatic lipid metabolism, cannot currently be excluded. Further
      research is needed to evaluate the relative importance of exercise in the
      treatment of hepatic insulin resistance, specifically as it relates to lipid
      accumulation in the liver.

PMID- 15571428
TI  - Does overtraining exist? An analysis of overreaching and overtraining research.
AB  - Athletes experience minor fatigue and acute reductions in performance as a
      consequence of the normal training process. When the balance between training
      stress and recovery is disproportionate, it is thought that overreaching and
      possibly overtraining may develop. However, the majority of research that has
      been conducted in this area has investigated overreached and not overtrained
      athletes. Overreaching occurs as a result of intensified training and is often
      considered a normal outcome for elite athletes due to the relatively short time
      needed for recovery (approximately 2 weeks) and the possibility of a
      supercompensatory effect. As the time needed to recover from the overtraining
      syndrome is considered to be much longer (months to years), it may not be
      appropriate to compare the two states. It is presently not possible to discern
      acute fatigue and decreased performance experienced from isolated training
      sessions, from the states of overreaching and overtraining. This is partially the
      result of a lack of diagnostic tools, variability of results of research studies,
      a lack of well controlled studies and individual responses to training.The
      general lack of research in the area in combination with very few well controlled
      investigations means that it is very difficult to gain insight into the
      incidence, markers and possible causes of overtraining. There is currently no
      evidence aside from anecdotal information to suggest that overreaching precedes
      overtraining and that symptoms of overtraining are more severe than overreaching.
      It is indeed possible that the two states show different defining characteristics
      and the overtraining continuum may be an oversimplification. Critical analysis of
      relevant research suggests that overreaching and overtraining investigations
      should be interpreted with caution before recommendations for markers of
      overreaching and overtraining can be proposed. Systematically controlled and
      monitored studies are needed to determine if overtraining is distinguishable from
      overreaching, what the best indicators of these states are and the underlying
      mechanisms that cause fatigue and performance decrements. The available
      scientific and anecdotal evidence supports the existence of the overtraining
      syndrome; however, more research is required to state with certainty that the
      syndrome exists.

PMID- 15571429
TI  - Optimising exercise training in peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is an obstructive condition where the flow of
      blood through peripheral arteries is impeded. During periods of increased oxygen
      demand (e.g. during exercise), peripheral limb ischaemia occurs, resulting in the
      sensation of muscle pain termed 'claudication'. As a result of claudication,
      subjects' ability to exercise is greatly reduced affecting their quality of life.
      Although many treatment options for patients with PAD exist, exercise training is
      an effective and low-cost means of improving functional ability and quality of
      life. Currently, there are limited specific recommendations to assist the
      exercise prescription and programming of these individuals. This review
      summarises data from 28 exercise training studies conducted in patients with PAD
      and formulates recommendations based on their results. Exercise training for
      patients with PAD should involve three training sessions per week comprising 45
      minutes of intermittent treadmill walking in a supervised environment for a time
      period of 20 weeks or more. Encouragement and direction is given to further
      research aimed at investigating the effectiveness of training programmes in these
      patients.

PMID- 15571430
TI  - Biomechanics and pathophysiology of overuse tendon injuries: ideas on insertional
      tendinopathy.
AB  - Tendons behave viscoelastically and exhibit adaptive responses to conditions of
      increased loading and disuse. High-resolution, real-time ultrasound scanning
      confirms the applicability of these findings in human tendons in vivo. In
      addition, recent biomechanical studies indicate that strain patterns in tendons
      may not be uniform, as tendons show stress-shielded areas and areas subjected to
      compressive loading at the enthesis. These areas correspond to the sites where
      tendinopathic characteristics are typically seen. This indicates that some
      tendinopathies may, paradoxically, be considered as 'underuse' lesions despite
      the common beliefs that they are overuse injuries. Classic inflammatory changes
      are not frequently seen in chronic athletic tendon conditions and histopathology
      features in tendinopathic tendons are clearly different from normal tendons,
      showing an exaggerated dysfunctional repair response. Tendinopathies are
      traditionally considered overuse injuries, involving excessive tensile loading
      and subsequent breakdown of the loaded tendon. Biomechanical studies show that
      the strains within the tendons near their insertion site are not uniform. If the
      material properties are similar throughout the tendon, forces transferred through
      the insertion site preferentially load the side of the tendon that is usually not
      affected initially in tendinopathy. In that case, the side affected by
      tendinopathy is generally 'stress shielded'. Thus, the presence of differential
      strains opens the possibility of alternative biomechanical explanations for the
      pathology found in these regions of the tendon. The traditional concept of
      tensile failure may not be the essential feature of the pathomechanics of
      insertional tendinopathy. Certain joint positions are more likely to stress the
      area of the tendon commonly affected by tendinopathy. Incorporating different
      joint position exercises may exert more controlled stresses on these affected
      areas of the tendon, possibly allowing better maintenance of the mechanical
      strength of that tendon region and, therefore, prevent injury. Such exercises
      could stress a healing area of the tendon in a controlled manner and thus
      stimulate healing once an injury has occurred. Additional work is needed to prove
      whether such principles should be incorporated in current rehabilitation
      techniques.

PMID- 15571431
TI  - PhotochemCAD 2: a refined program with accompanying spectral databases for
      photochemical calculations.
AB  - The PhotochemCAD program has been revised extensively. Calculations can be
      performed using eight modules (oscillator strength, transition dipole moment and
      natural radiative lifetime, Forster energy transfer, multicomponent analysis,
      blackbody radiator, artificial spectrum creation, transmission calculation, and
      analysis of energy transfer among linear multichromophore arrays). The user
      interface has been streamlined to facilitate visual display, operation of the
      various modules, input of user data via a wizard and output of spectra and
      calculations. The database of absorption and fluorescence spectra has been
      expanded to 150 photochemically relevant compounds. A database of solar spectra
      has been added. The program runs under Windows and is equipped with extensive
      literature references and help features, including a tutorial section with video
      files.

PMID- 15571432
TI  - Eye movements and behavioral responses to threatening and nonthreatening stimuli
      during visual search in phobic and nonphobic subjects.
AB  - Spider-phobic and nonphobic subjects searched for a feared/fear-relevant (spider)
      or neutral target (mushroom) presented in visual matrices of neutral objects
      (flowers). In half of the displays, the mushroom target was paired with a spider
      distractor, or a spider target was paired with a mushroom distractor. Although
      all subjects responded faster to the neutral target than to the feared/fear
      relevant target, phobics were slower to respond than nonphobics when a mushroom
      target was presented with a spider distractor. Their eyes appeared to be drawn to
      the feared distractor before fixating neutral targets. A further experiment
      indicated no group differences when subjects merely judged the homogeneity of
      matrices. Thus, threat seems to capture the attention of phobics only when it is
      part of a background that subjects are explicitly instructed to ignore.

PMID- 15571433
TI  - Fear and the amygdala: manipulation of awareness generates differential cerebral
      responses to phobic and fear-relevant (but nonfeared) stimuli.
AB  - Rapid response to danger holds an evolutionary advantage. In this positron
      emission tomography study, phobics were exposed to masked visual stimuli with
      timings that either allowed awareness or not of either phobic, fear-relevant
      (e.g., spiders to snake phobics), or neutral images. When the timing did not
      permit awareness, the amygdala responded to both phobic and fear-relevant
      stimuli. With time for more elaborate processing, phobic stimuli resulted in an
      addition of an affective processing network to the amygdala activity, whereas no
      activity was found in response to fear-relevant stimuli. Also, right prefrontal
      areas appeared deactivated, comparing aware phobic and fear-relevant conditions.
      Thus, a shift from top-down control to an affectively driven system optimized for
      speed was observed in phobic relative to fear-relevant aware processing.

PMID- 15571434
TI  - Semantic priming of different affective categories.
AB  - The authors investigated affective semantic priming using a lexical decision task
      with 4 affective categories of related word pairs: neutral, happy, fearful, and
      sad. Results demonstrated a striking and reliable effect of affective category on
      semantic priming. Neutral and happy prime-targets yielded significant semantic
      priming. Fearful pairs showed no or modest priming facilitation, and sad primes
      slowed reactions to sad targets. A further experiment established that affective
      primes do not have generalized facilitatory-inhibitory effects. The results are
      interpreted as showing that the associative mechanisms that support semantic
      priming for neutral words are also shared by happy valence words but not for
      negative valence words. This may reflect increased vigilance necessary in adverse
      contexts or suggest that the associative mechanisms that bind negative valence
      words are distinct.

PMID- 15571435
TI  - Early manifestations of personality and adult emotional functioning.
AB  - Developmental antecedents to adult emotional functioning were investigated in an
      epidemiologic study using theories of personality and emotion. The authors tested
      whether different types of adult emotional distress can be linked to childhood
      personality attributes. Using data from 3,138 children at age 7, measures of 4
      childhood personality attributes were developed and validated: Behavioral
      Inhibition, Distress Proneness, Attention, and Inappropriate Interpersonal Self
      Regulation. Sound psychometric properties of these scales are demonstrated by
      considering the measures across multiple samples and in comparison with
      established child behavior measures. Emotional distress measures were obtained
      for 694 of these individuals at age 35. Of the personality attributes, 3 of 4
      (except behavioral inhibition) predicted general levels of distress as well as
      specific aspects of adult emotional functioning.

PMID- 15571436
TI  - Facial appearance, gender, and emotion expression.
AB  - Western gender stereotypes describe women as affiliative and more likely to show
      happiness and men as dominant and more likely to show anger. The authors assessed
      the hypothesis that the gender-stereotypic effects on perceptions of anger and
      happiness are partially mediated by facial appearance markers of dominance and
      affiliation by equating men's and women's faces for these cues. In 2 studies,
      women were rated as more angry and men as more happy-a reversal of the
      stereotype. Ratings of sadness, however, were not systematically affected. It is
      posited that markers of affiliation and dominance, themselves confounded with
      gender, interact with the expressive cues for anger and happiness to produce
      emotional perceptions that have been viewed as simple gender stereotypes.

PMID- 15571437
TI  - Beyond surprise: the puzzle of infants' expressive reactions to expectancy
      violation.
AB  - The reactions of 58 infants to expectancy violation by digitally filtering the
      experimenter's voice were studied in a cross-sectional design for ages 5, 7, 9,
      11-12, and 14 months. The results show that behavioral freezing and changes in
      gaze direction, but not facial or vocal expression, are reliable responses to
      expectancy violation. The pattern suggests that a transition in the infant's
      capacity for cognitive evaluation of novel and discrepant events may occur around
      age 9 months. These findings confirm the consistent failure to find prototypical
      facial surprise reactions in research on novel or impossible situations.
      Componential theories of emotion, which predict adaptive behavior patterns from
      appraisal processes, may provide clues for underlying mechanisms and generate
      hypotheses on age-related changes in emotional expression.

PMID- 15571438
TI  - The lateralized emotional stroop task: left visual field interference in women.
AB  - In a visual hemifield emotional Stroop task, 54 women were asked to name the
      color of laterally flashed emotional and neutral words while ignoring their
      semantic content. Vocal reaction times for color naming were recorded. The
      participants exhibited significant emotional interference effects in the left
      visual field, which tended to be larger for negative words than for positive
      words. Participants with higher trait anxiety scores exhibited larger
      interference for positive words in the left relative to the right visual field.
      The outcome indicates that, in women, emotional Stroop interference arises in the
      right rather than in the left hemisphere, with a larger impact of negative than
      of positive words, and with trait anxiety modulating the lateralized interference
      for positive words.

PMID- 15571439
TI  - Measuring adolescent drug abuse and psychosocial factors in four ethnic groups of
      drug-abusing boys.
AB  - There is an absence of empirical work on the measurement of adolescent drug abuse
      among non-White ethnic youths. The field would benefit from psychometrically
      sound measures for ethnic groups. The psychometric properties of a multi-scale
      assessment tool for adolescent drug abuse, the Personal Experience Inventory
      (PEI), have been examined largely in White samples. The current study reports
      reliability and validity data for the PEI across four samples of boys (White,
      African American, Native American, and Hispanic). The results provide general
      psychometric support for the non-White groups. The use and limitations of the PEI
      in different ethnic/racial groups are discussed.

PMID- 15571440
TI  - The discriminative stimulus effects of cocaine in a pavlovian sexual approach
      paradigm in male Japanese quail.
AB  - Two groups of male Japanese quail (Coturnix japonica) were trained [corrected] to
      discriminate cocaine from saline in a conditioned approach procedure maintained
      by sexual reinforcement. For 1 group, cocaine (10 mg/kg ip) was administered
      prior to a conditioned stimulus (CS) that predicted copulation; saline followed
      by a CS predicted no copulation. A second group underwent the opposite training
      regimen. Results revealed apparent between-group differences in the rates of
      acquisition of the discrimination; however, during extinction trials, both groups
      responded more under the drug condition that predicted the female than to the
      condition that predicted no female. The results suggested that a drug
      discrimination may be maintained by sexual reinforcement. The findings are
      discussed with regard to interactions of cocaine and sexual reward, as well as to
      Pavlovian conditional stimulus control.

PMID- 15571441
TI  - Alcohol-induced impairment of inhibitory mechanisms involved in visual search.
AB  - The present study examined the effects of alcohol on the ability to perform a
      cued target detection task that measured inhibition of return (IOR). IOR is a
      reflexive inhibitory mechanism that delays attention from returning to a
      previously attended location and has been shown to increase the efficiency of a
      visual search. Ten social drinkers performed the task under 3 alcohol doses: 0.0
      g/kg (placebo), 0.45 g/kg, and 0.65 g/kg. The results showed both active alcohol
      doses reduced the IOR effect by shortening its duration of influence. The reduced
      duration of IOR under alcohol suggests that repeated searches in previously
      explored locations might be more likely under the drug, thereby reducing search
      efficiency.

PMID- 15571442
TI  - Delay discounting of potentially real and hypothetical rewards: II. Between- and
      within-subject comparisons.
AB  - Prior studies comparing discounting of delayed hypothetical or potentially real
      rewards have reported no differences, but they used within-subjects designs. This
      raises the possibility that participants remembered their choices in one
      condition and repeated them in the other. In Experiment 1, between-subjects
      comparisons were made with an adjusting-amount procedure. No significant effect
      of reward type on delay discounting was detected. Experiment 2 increased the
      proportion of real rewards and made between- and within-subject comparisons.
      These comparisons also failed to reveal a significant effect of reward type.
      Although these findings are consistent with prior findings, caution is urged
      because choices involving hypothetical rewards have yet to be compared with
      choices involving real rewards (i.e., the consequences of every choice are
      obtained) in an experiment using forced-choice trials and steady-state
      methodology.

PMID- 15571443
TI  - Abstinence incentive effects in a short-term outpatient detoxification program.
AB  - Despite being widely available, outpatient detoxification has limited efficacy as
      a stand-alone treatment. This study examined whether abstinence-contingent
      incentives would improve outcomes for patients entering outpatient opiate
      detoxification. Participants (N = 211) received a 100 US dollars voucher on the
      last day of detoxification either contingent on opiate and cocaine abstinence or
      noncontingently. Urine samples were collected at intake, on Wednesday, Friday
      (the last day of detoxification), and the following Monday. Among contingent
      voucher participants, 31% were drug-free on Friday compared with 18% of
      noncontingent controls (Z = 2.4, p < .05). Few (12-13%) participants tested
      negative on Monday. Results support the ability of vouchers to produce modest
      improvements in abstinence initiation rates during brief detoxification but
      suggest that additional interventions are needed to sustain improvements.

PMID- 15571444
TI  - Cocaine abstinence during methadone maintenance: effects of repeated brief
      exposure to voucher-based reinforcement.
AB  - This study determined whether abstinence engendered by intermittent reinforcement
      might generalize to nonreinforced periods and enhance overall rates of cocaine
      abstinence among methadone maintenance patients. Participants were randomized to
      1 of 3 groups. The quantitative group (n = 14) earned incentives for a 50%
      decrease in urine benzoylecgonine concentrations; the qualitative group (n = 13)
      earned incentives for providing urines with concentrations <300 ng/ml. Both
      reinforced groups received 12 random opportunities to earn 100 US dollars in
      vouchers for abstinence. The control group (n = 15) was encouraged to abstain on
      12 occasions under the same schedule. Incentive participants achieved
      significantly more cocaine abstinence on earning than on nonearning days, with no
      difference between quantitative and qualitative groups. The study supports brief
      abstinence test efficacy but did not find that unpredictable opportunities to
      earn incentives generalized to nonreinforced days.

PMID- 15571445
TI  - An experimental examination of the initial weeks of abstinence in cigarette
      smokers.
AB  - Gaining experimental control over abstinence may help define processes that
      change during abstinence that may be related to the association between initial
      abstinence and relapse risk often noted in clinical trials. Adult smokers (n =
      34) were randomly assigned to receive monetary incentives contingent on
      abstinence (CO +/- 4 ppm) or noncontingent for 12 days. Carbon monoxide (CO)
      tests were conducted 3 times per day, saliva samples were collected on Days 5 and
      12, and all other measures were collected 1 time per day. In the contingent
      group, 59% of participants abstained throughout the study versus 0% in the
      control condition. Abstinence was associated with increases in participant-rated
      ease of abstaining and confidence in abstinence; nicotine withdrawal severity and
      craving decreased over time. Results indicate that it is feasible to
      experimentally manipulate smoking abstinence and that doing so can enhance
      understanding of the relationship between early abstinence and relapse risk.

PMID- 15571446
TI  - Effects of alcohol and expectancies on HIV-related risk perception and behavioral
      skills in heterosexual women.
AB  - This experiment tested the effects of alcohol and expectancies on determinants of
      safer sex according to the information-motivation-behavioral skills model. Sixty
      heterosexual women attended 2 sessions. During Session 1, participants completed
      a set of descriptive measures; during Session 2 they were randomly assigned to 1
      of 4 beverage conditions: control, alcohol-low (.35 gm alcohol/kg body weight),
      alcohol-moderate (.70 gm alcohol/kg body weight), or placebo. After beverage
      consumption, all participants completed measures of motivation to engage in risky
      sex and condom use negotiation skills. Results showed that the higher dose of
      alcohol and stronger alcohol expectancies were associated with greater motivation
      to engage in risky sexual behavior. However, perceived intoxication, rather than
      actual alcohol consumption or expectancies, was the best predictor of condom use
      negotiation skills. Integration of the findings with past research and their
      implication for the design of HIV-prevention programs are discussed.

PMID- 15571447
TI  - Gender, alcohol consumption, and differing alcohol expectancy dimensions in
      college drinkers.
AB  - Examinations of gender differences in alcohol expectancies among college drinkers
      typically have used self-report measures to assess single expectancy dimensions
      and often have been confounded by drinking level. This study examined gender
      differences in alcohol expectancies using 2 assessment methods. College students
      (N = 88) completed self-report questionnaires, including expectancy likelihood
      and subjective evaluation endorsements of expectancies, and a computerized
      expectancy accessibility task. Expectancy accessibility and endorsement were
      modestly correlated, with higher alcohol consumption and female gender linked to
      greater accessibility and endorsement of social enhancement expectancies. Gender
      moderated the relation between consumption and sociability expectancy
      accessibility; among men, heavier drinking was associated with more rapid
      activation of expectancies. Findings suggest complexity in associations among
      these variables and underscore the need to capture the multidimensionality of the
      expectancy construct and its relationship to alcohol use.

PMID- 15571448
TI  - Injectable cartilage tissue engineering.
AB  - Cartilage is the tissue that lines the surface of bones in articulating joints,
      allowing painless joint movement. Cartilage loss is an increasingly significant
      problem, particularly with the ageing of active baby boomers, with few
      efficacious treatments available at present. Tissue engineering is a field that
      has evolved over recent years to combat tissue loss by providing a living tissue
      equivalent or substitute that can mimic the properties of the lost tissue. The
      general strategy of tissue engineering is to place cells on a biomaterial
      scaffold that is designed to promote cell function and form new tissue. This
      review describes the status of materials that are available as injectable
      scaffolds for tissue engineering and the numerous cell types that can be applied
      to cartilage repair, including cells derived from cartilage and stem cells. The
      current state of injectable cartilage tissue engineering and the hurdles that
      remain for widespread clinical application are discussed.

PMID- 15571449
TI  - Cell therapy for neuropathic pain in spinal cord injuries.
AB  - Cell therapy to treat neuropathic pain after spinal cord injury (SCI) is in its
      infancy. However, the development of cellular strategies that would replace or be
      used as an adjunct to existing pharmacological treatments for neuropathic pain
      have progressed tremendously over the past 20 years. The earliest cell therapy
      studies for pain relief tested adrenal chromaffin cells from rat or bovine
      sources, placed in the subarachnoid space, near the spinal cord pain- processing
      pathways. These grafts functioned as cellular minipumps, secreting a cocktail of
      antinociceptive agents around the spinal cord for peripheral nerve injury,
      inflammatory or arthritic pain. These initial animal, and later clinical, studies
      suggested that the spinal intrathecal space was a safe and accessible location
      for the placement of cell grafts. However, one major problem was the lack of a
      homogeneous, expandable cell source to supply the antinociceptive agents. Cell
      lines that can be reversibly immortalised are the next phase for the development
      of a practical, homogenous cell source. These technologies have been modelled
      with a variety of murine cell lines, derived from embryonic adrenal medulla or
      CNS brainstem, in which cells are transplanted, which downregulate their
      proliferative, oncogenic phenotype either before or after transplant. An
      alternative approach for existing human cell lines is the use of neural or
      adrenal precursors, in which the antinociceptive properties are induced by in
      vitro treatment with molecules that move the cells to an irreversible neural or
      chromaffin, and non-oncogenic, phenotype. Although such human cell lines are at
      an early stage of investigation, their clinical antinociceptive potential is
      significant given the daunting problem of difficult-to-treat neuropathic SCI
      pain.

PMID- 15571450
TI  - Myoblast transplantation for inherited myopathies: a clinical approach.
AB  - Myoblast transplantation (MT) is an experimental strategy for the potential
      treatment of myopathies. MT has two properties that make it potentially
      beneficial: genetic complementation and myogenic potential. Preclinical
      experiments on monkeys have shown that promising results can be obtained with MT
      in large muscles of primates depending on two conditions: appropriate
      immunosuppression and cell delivery by a method of high-density injections.
      Preclinical work on MT is being, or may be, addressed to: develop efficient
      methods of donor cell delivery applicable to clinics; control or avoid acute
      rejection by methods with the fewest secondary effects; understand the factors
      that condition the early survival of donor cells following transplantation;
      increase the success of each individual injection; re-engineer a functional
      structure in muscles that degenerates to fibrosis and fat substitution; and
      search for precursor cells with potential advantages over myoblasts.

PMID- 15571451
TI  - Th1/Th2 cells in inflammatory disease states: therapeutic implications.
AB  - Inflammation is initiated as a protective response by the host, but can often
      result in systemic pathology. Among cells of the immune system, T lymphocytes
      play a major role in the inflammatory response. T cell inflammation is
      characterised histologically by an infiltration of mononuclear cells. Key
      regulators of this response are a subset of T lymphocytes called T helper (Th)
      cells. These cells secrete soluble mediators called cytokines, which orchestrate
      the immune response. The appropriate regulation of Th cell immunity is critical
      in the control and prevention of diverse disease states. This review will focus
      on the role of Th cells in the inflammatory process involved in allergic disease,
      diabetes, infectious disease, rheumatoid arthritis, heart disease, multiple
      sclerosis and cancer. In the area of autoimmunity, in particular, a basic
      understanding of Th cells and cytokines has contributed to the development of
      clinically efficacious biological agents. This review also examines current and
      novel treatment strategies under investigation at present that regulate Th cell
      immunity, which may result in better treatments for immune-mediated diseases.

PMID- 15571452
TI  - The colony-stimulating factors: use to prevent and treat neutropenia and its
      complications.
AB  - The colony-stimulating factors (CSFs) represent the only biological response
      modifiers used in clinical practice to treat or prevent neutropenia. These
      pleiotropic cytokines are available in clinical practice as granulocyte CSF (G
      CSF), granulocyte-macrophage CSF (GM-CSF) and pegylated G-CSF. Neutropenia and
      its complications, most importantly febrile neutropenia (FN), remain major and
      serious side effects of cancer chemotherapy. Several studies and meta-analyses
      have addressed the clinical applications of CSFs to treat or prevent neutropenia.
      Guidelines have been developed to foster the appropriate use of CSFs. This
      article reviews the nature and use of the CSFs, and summarises the critical
      studies and guidelines. A historical perspective briefly describes the discovery,
      synthesis and clinical use of CSFs. The major biological and pharmacological
      characteristics are highlighted. The clinical applications of the CSFs are
      reviewed, including primary FN prophylaxis, secondary FN prophylaxis, treatment
      of FN, support of dose-dense chemotherapy regimens, use in leukaemia and
      myelodysplastic syndromes, utility in stem cell transplantation, and use in
      elderly and paediatric patients. Finally, clinical efficacy data, as well as the
      economic impact of the CSFs, are discussed.

PMID- 15571453
TI  - Vascular-targeted cancer gene therapy.
AB  - As a consequence of the dramatic progress that has been made in recent years
      towards elucidating the diverse molecular events involved in the development and
      pathogenesis of malignant disease, there is now no shortage of genes that can be
      exploited or targeted in the context of cancer gene therapy. Many of these have
      been shown to be effective both in vitro and in various animal models, and a
      number have progressed to the clinic. The results of these later studies,
      although generally encouraging, are perhaps less dramatic than one might have
      hoped. Although a number of factors undoubtedly contribute to this finding, it is
      evident that a major reason relates to the difficulties implicit in achieving
      efficient in vivo gene transfer, particularly in a clinical context. Targeting
      gene therapy, not to the malignant population, but instead to the vasculature
      upon which the survival and growth of a tumour depends constitutes an alternative
      approach that overcomes some of the delivery problems associated with established
      tumour cell-directed strategies.

PMID- 15571454
TI  - RNA interference as a potential tool in the treatment of leukaemia.
AB  - Leukaemias are often characterised by nonrandom chromosomal translocations that,
      at the molecular level, induce the activation of specific oncogenes or create
      novel chimeric genes. They have frequently been regarded as optimal targets for
      gene silencing approaches, as these single abnormalities may directly initiate or
      maintain the malignant process. Since the ground-breaking discovery that double
      stranded RNA molecules 21 - 23 nucleotides in length, named small interfering
      RNAs (siRNAs), are able to elicit gene-specific inhibition also in mammalian
      cells, the interest of the scientific community has rapidly been drawn to the
      potential of these siRNAs for targeting oncogenic fusion genes in leukaemic
      cells. There has been a flurry of reports describing overexpressed or mutated
      genes that may also serve as attractive targets for therapeutic intervention by
      RNA silencing methods. Although this approach seems to be relatively
      straightforward, many problems remain to be solved before siRNAs may become
      clinically implemented as 'leukaemia drugs'. Difficulties in delivering siRNAs
      into the leukaemic cell, inefficient target mRNA cleavage, prolonged protein half
      life in cancer cells, nonspecific side effects caused by targeting other genes
      than those originally thought, immunological reactions of the host organism
      against the siRNAs, such as interferon responses, or even acquired resistance
      mechanisms, such as escape mutants, should be overcome. This paper reviews the
      current knowledge regarding the use of siRNAs, either chemically synthesised or
      intracellular-generated via specialised expression constructs, in order to
      suppress the falsely activated oncogenes in haematopoietic malignancies.

PMID- 15571455
TI  - Prospects of antisense oligodeoxynucleotides to alleviate renal ischaemia
      reperfusion injury.
AB  - Renal ischaemia-reperfusion (I/R) injury is a clinically significant problem and
      an invariable consequence of renal transplantation. The problem begins at the
      onset of acute tubular necrosis (ATN), when the transplantation takes a long
      ischaemic interval by using the cardiac arrest donor's kidney. In addition, the
      longer the ischaemic interval, the higher the incidence rate of ATN. It is
      clinically important that renal I/R injury is reduced. The antisense
      oligodeoxynucleotide (AS-ODN), developed as a therapy for intractable diseases at
      the gene level, has recently been established as an important method in examining
      specific gene functions. The authors have previously demonstrated that AS
      ODN/tissue factor (TF) prevents renal I/R injury. This review discusses the
      efficacy of AS-ODN/TF and AS-ODN/intercellular adhesion molecule-1 as existing
      targets, and the potential of AS-ODN/nuclear factor-kappaB, AS-ODN/cyclooxygenase
      and AS-ODN/5-lipoxygenase as prospective targets.

PMID- 15571456
TI  - Vaccines against cholera, typhoid fever and shigellosis for developing countries.
AB  - Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a
      significant burden, especially among the poor in countries where these illnesses
      are endemic. Older-generation, parenteral, whole-cell vaccines against cholera
      and typhoid fever were abandoned in many countries as public health tools because
      of problems with insufficient protection and/or inadequate safety profiles.
      Modern-generation licensed vaccines are available for cholera and typhoid fever,
      but are not widely used by those in greatest need. A number of experimental
      candidates exist for all three diseases. Future research should focus on
      generating the evidence necessary to obtain a consensus on the deployment of
      existing vaccines against cholera and typhoid fever, and on clinical evaluation
      of pipeline vaccine candidates against all three diseases.

PMID- 15571457
TI  - Mannose receptor-targeted vaccines.
AB  - Targeting antigens to endocytic receptors on professional antigen-presenting
      cells (APCs) represents an attractive strategy to enhance the efficacy of
      vaccines. Such APC-targeted vaccines have an exceptional ability to guide
      exogenous protein antigens into vesicles that efficiently process the antigen for
      major histocompatibility complex class I and class II presentation. Efficient
      targeting not only requires high specificity for the receptor that is abundantly
      expressed on the surface of APCs, but also the ability to be rapidly internalised
      and loaded into compartments that contain elements of the antigen-processing
      machinery. The mannose receptor (MR) and related C-type lectin receptors are
      particularly designed to sample antigens (self and non-self), much like pattern
      recognition receptors, to integrate the innate with adaptive immune responses. In
      fact, a variety of approaches involving delivery of antigens to the MR have
      demonstrated effective induction of potent cellular and humoral immune responses.
      Yet, although several lines of evidence in diverse experimental systems attest to
      the efficacy of targeted vaccine strategies, it is becoming increasingly clear
      that additional signals, such as those afforded by adjuvants, may be critical to
      elicit sustained immunity. Therefore, MR-targeted vaccines are likely to be most
      efficacious in vivo when combined with agents that elicit complementary
      activation signals. Certainly, a better understanding of the mechanism associated
      with the induction of immune responses as a result of targeting antigens to the
      MR, will be important in exploiting MR-targeted vaccines not only for mounting
      immune defenses against cancer and infectious disease, but also for specific
      induction of tolerance in the treatment of autoimmune disease.

PMID- 15571458
TI  - Thalidomide-derived immunomodulatory drugs as therapeutic agents.
AB  - Thalidomide, a drug originally used to treat morning sickness, was removed from
      the market place in the early 1960s after it was found to cause serious
      congenital birth defects. However, thalidomide has recently been investigated in
      a new light following its activity in a number of chronic diseases. Moreover,
      like thalidomide itself, its second-generation immunomodulatory drug (IMiD)
      analogues have been shown to act as powerful anticancer agents and are clearly
      active in the treatment of patients with relapsed multiple myeloma. These new
      drugs, in particular the second-generation IMiDs, lenalidomide (CC-5013,
      REVLIMID; Celgene Corp., NJ, USA) and CC-4047 (ACTIMID; Celgene Corp.), offer
      improvements over thalidomide (a first-generation IMiD) in terms of efficacy and
      safety in human studies. The key to the therapeutic potential of IMiDs lies in
      the fact that the drugs have multiple mechanisms of action, which may produce
      both anti-inflammatory and antitumour effects. These effects are probably
      contextual, depending both on the cell type and the stimulus involved. Mechanisms
      associated with IMiD activity include TNF-alpha-inhibitory, T cell costimulatory
      and antiangiogenic activities. Studies of the mechanisms of action of these drugs
      are ongoing and will facilitate the continued development of this class of
      compound in a number of diseases.

PMID- 15571459
TI  - Prevention of calcification in bioprosthetic heart valves: challenges and
      perspectives.
AB  - Surgical replacement with artificial devices has revolutionised the care of
      patients with severe valvular diseases. Mechanical valves are very durable, but
      require long-term anticoagulation. Bioprosthetic heart valves (BHVs), devices
      manufactured from glutaraldehyde-fixed animal tissues, do not need long-term
      anticoagulation, but their long-term durability is limited to 15 - 20 years,
      mainly because of mechanical failure and tissue calcification. Although
      mechanisms of BHV calcification are not fully understood, major determinants are
      glutaraldehyde fixation, presence of devitalised cells and alteration of specific
      extracellular matrix components. Treatments targeted at the prevention of
      calcification include those that target neutralisation of the effects of
      glutaraldehyde, removal of cells, and modifications of matrix components. Several
      existing calcification-prevention treatments are in clinical use at present, and
      there are excellent mid-term clinical follow-up reports available. The purpose of
      this review is to appraise basic knowledge acquired in the field of prevention of
      BHV calcification, and to provide directions for future research and development.

PMID- 15571460
TI  - Is vaccine therapy the future in cancer prevention?
AB  - One vaccine designed to prevent cancer by preventing a precursor infection is
      already in common use, and at least one more is in the latter stages of clinical
      development. These vaccines are part of a new era of cancer immunoprophylaxis.
      Several further vaccines are in preclinical and clinical development, targeted at
      preventing cancer precursor infections, and these should add to our ability to
      prevent this common human disorder. However, vaccines to prevent cancers not
      triggered by infection are a more remote prospect, for a variety of reasons.

PMID- 15571461
TI  - Recombinant human thyrotropins of the twenty-first century.
AB  - In recent years, many new recombinant protein therapeutics have been developed
      and tested in clinical trials [1]. Current and future clinical uses of
      recombinant human thyroid-stimulating hormone (rhTSH; Thyrogen, Genzyme) in
      thyroid diseases are discussed in the review published in this issue of Expert
      Opinion on Pharmacotherapy [2]. As Thyrogen is a wild-type rhTSH produced in
      Chinese hamster ovary cells, it has relatively low affinity to the human TSH
      receptor. Such low affinity and weak intrinsic bioactivity of rhTSH, compared to
      the bovine or rodent TSH, may help to explain the results of several studies
      indicating limited clinical efficacy of Thyrogen. TSH analogues with largely
      increased receptor affinity, potency and efficacy, are expected to provide not
      only more effective than currently used diagnostic methods, but should also serve
      as indispensable second-generation thyrotropins for the diagnosis and treatment
      of thyroid carcinomas with a largely limited number of TSH receptors.

PMID- 15571462
TI  - Current chemotherapeutic treatment of malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma is an aggressive malignancy which is almost always
      fatal; median survival is usually < 1 year. Most patients present with symptoms
      including pain, dyspnoea, pleural effusions and chest wall masses. Until
      recently, there has been no effective treatment which can improve symptoms and
      prolong survival. This article reviews recent developments in the treatment of
      mesothelioma, particularly advances in drug therapy and the use of the current
      most active drug combination: pemetrexed and cisplatin. Pemetrexed is a novel
      antifolate drug with multiple enzyme targets. The combination of pemetrexed and
      cisplatin demonstrated a survival advantage over cisplatin alone in patients with
      pleural mesothelioma, and can give symptomatic benefits. This combination has
      become the standard of care in mesothelioma treatment.

PMID- 15571463
TI  - Therapeutic spectrum in the treatment of myelodysplastic syndromes.
AB  - During the last 15 years, important progress has been made in the understanding
      of the biology and prognosis of myelodysplastic syndromes (MDS). It is a clonal
      disorder, characterised by ineffective haematopoiesis, which can lead to either
      fatal cytopenias or acute myelogenous leukaemias. Risk-adapted treatment
      strategies were established, due to the high median age (60 - 75 years) of the
      MDS patients and the individual history of the disease (i.e. number of
      cytopenias, cytogenetic changes, transfusion requirements). Allogeneic bone
      marrow transplantation currently offers the only potentially curative treatment,
      but this form of therapy is not available for the 'typical' MDS patient, who is >
      60 years of age. Therapy with erythropoietin and granulocyte colony-stimulating
      factor has improved the quality of life of selected patients. The development of
      target-specific therapies, including antibodies and small molecules directed
      against specific molecular alterations in MDS, with minimal adverse effects, is
      the hope for the future. Furthermore, the innovative use of immunomodulatory
      agents and the optimising of cytotoxic treatment should continue to help in the
      treatment of MDS.

PMID- 15571464
TI  - The Japanese experiences with hypoxia-targeting pharmacoradiotherapy: from
      hypoxic cell sensitisers to radiation-activated prodrugs.
AB  - Tumour hypoxia is a negative factor in cancer radiotherapy. In order to overcome
      the problem, various pharmacotherapies have been investigated as an adjunct to
      radiotherapy. The use of hypoxic cell sensitisers is a classical strategy, and
      many new compounds have been developed and investigated. Development of more
      efficient compounds than those currently available seems difficult and clinical
      studies to prove the efficacy of the existing compounds are encouraged,
      especially in combination with radiosurgery, intraoperative radiotherapy, and
      interstitial irradiation, in which a single high dose of radiation is used.
      Following the advent of hypoxic cell sensitisers, hypoxic cytotoxins have become
      available. Among them, tirapazamine has already gained success when combined with
      cisplatin in non-small cell lung cancer. The beneficial effect of tirapazamine
      when combined with radiation needs to be determined. As a third-generation
      compound in this field, antitumour prodrugs that are activated by irradiation
      under hypoxic conditions via one-electron reduction have been proposed. Prodrugs
      of 5-fluorouracil and 5-fluoro-2'-deoxyuridine have shown in vivo as well as in
      vitro activity. Although clinical evaluation of the compounds is not warranted
      due to a relatively low in vivo effect, this strategy appears promising if the
      prodrug design can be applied to more potent agents that shall be developed in
      future.

PMID- 15571465
TI  - The effectiveness of combining hormone therapy and radiotherapy in the treatment
      of prostate cancer.
AB  - Hormone therapy is commonly used for many patients with prostate cancer.
      Radiotherapy occupies a prominent role in the treatment of locally-advanced,
      localised, and postsurgical prostate cancer. Hormone therapy and radiotherapy are
      often used in combination. In this article, the major features of the
      hormone/radiotherapy interactions are reviewed, with emphasis on the role of
      combination treatment for locoregional disease. The reported results suggest a
      biochemical survival advantage to the use of hormone therapy with radiotherapy,
      in virtually all settings of non-metastatic disease, with the weakest database
      being in the setting of low-risk, early-stage disease. Further data are needed in
      order to identify the optimum target population, combination of agents, and
      hormone duration, as a function of patient and disease factors.

PMID- 15571466
TI  - Chemotherapeutic options in the management of anal cancer.
AB  - During the past two decades, anal cancer has served as a paradigm for the
      successful application of chemoradiation to solid tumours; so far, it remains one
      of the few carcinomas of the gastrointestinal tract which are curable without the
      need for definitive surgery. Since the original contribution by Nigro in 1974,
      surprisingly few changes have been made to the standard of care in chemotherapy,
      which still consists of a combination of 5-fluorouracil and mitomycin C. However,
      many issues have yet to be clarified, such as the potential role of cisplatin as
      a substitute to mitomycin, as well as treatment-induced toxicity in HIV-positive
      patients. In this paper, the management of patients with anal cancer is
      presented, and new chemotherapeutic options are critically reviewed. Finally, the
      authors' opinion regarding currently unresolved issues in the treatment of these
      rare neoplasms is expressed.

PMID- 15571467
TI  - Botanical medicine and cancer: a review of the safety and efficacy.
AB  - It is currently estimated that > 50% of all patients diagnosed with cancer
      explore complementary and alternative medicine - especially herbal medicine. We
      conducted a comprehensive review to assess the safety and efficacy of herbal
      medicines commonly used by patients in an attempt to: prevent cancer; treat
      cancer; and treat adverse effects associated with conventional cancer treatments.
      Current evidence suggests that Asian ginseng, garlic, green tea, tomatoes and soy
      intake as part of the diet may be useful in preventing various cancers;
      additional research is needed in order to determine the efficacy of essiac,
      evening primrose oil, mistletoe, reishi, shiitake and turmeric as cancer
      treatments; and ginger may be effective in treating chemotherapy-induced nausea
      and vomiting.

PMID- 15571468
TI  - Clinical uses of recombinant human thyrotropin.
AB  - Recombinant human thyroid-stimulating hormone (rhTSH), used to enhance diagnostic
      radioiodine whole body scanning and thyroglobulin testing, has dramatically
      altered the management of patients with thyroid cancer. Withdrawal from thyroid
      hormone suppression therapy and subsequent hypothyroidism is no longer the only
      safe and effective method for thyroid cancer surveillance. Currently, rhTSH is
      only approved for the monitoring of low-risk patients with well-differentiated
      thyroid cancer and radioactive iodine administration, in selected cases.
      Additional applications of rhTSH include enhancing the sensitivity of positron
      emission tomography in thyroid cancer, the management of multinodular goiter, and
      dynamic testing of thyroid reserve. The diagnostic and therapeutic role of rhTSH
      in these areas is discussed in this review.

PMID- 15571469
TI  - Immune thrombocytopenic purpura - current management practices.
AB  - The treatment of patients with immune thrombocytopenic purpura (ITP) is changing
      rapidly, as new agents demonstrate the capability of improving outcomes and
      decreasing toxicity. Prior to 1981, the only effective treatment options
      available to increase platelet counts in persons with ITP were corticosteroids
      and splenectomy. In recent years, intravenous immunoglobulin (IVIg) and
      intravenous Rh immunoglobulin (IV RhIg) have demonstrated efficacy comparable to
      that of corticosteroids for increasing platelet counts in ITP. In addition, IVIg
      and IV RhIg have demonstrated efficacy for maintaining corticosteroid-induced
      increased platelet counts by periodic infusion, causing a transient impairment of
      reticuloendothelial clearance function (medical splenectomy). Thus, the time
      proven efficacy of corticosteroids for initial treatment of ITP (induction) may
      now be supplemented with IVIg or IV RhIg infusions for patients requiring ongoing
      treatment to support a timely and complete steroid taper, while sustaining the
      increased platelet count (maintenance) with less toxicity. Several investigators
      have reported that rituximab (anti-CD20) induced sustained remissions with
      minimal toxicity, in patients with chronic ITP. These reports are promising and,
      if confirmed, will provide another effective (spleen-sparing) option for managing
      acute ITP and a long-awaited option for patients who have had a splenectomy and
      are refractory to conventional agents. Other treatments, including danazol,
      azathioprine, cyclophosphamide, vinca alkaloids and cyclosporin A, have
      advocates, but evidence of their efficacy is limited to relatively small and
      mostly uncontrolled clinical trials. In our opinion, these agents should be
      reserved for symptomatic thrombocytopenia after refractoriness to
      corticosteroids, IVIg, IV RhIg, splenectomy and rituximab has been clearly
      established.

PMID- 15571470
TI  - Economic assessment in the management of non-Hodgkin's lymphoma.
AB  - An increasing need for economic evaluations of non-Hodgkin's lymphoma (NHL)
      treatments exists. We performed a literature review on the currently available
      NHL economic evaluations, using PubMed and the Cochrane database. English and
      Dutch language papers on treatment in adults were selected. A total of 88
      publications were found, 44 of which were included. Of these, 6 economic
      evaluation-specific methodological items are evaluated (study perspective,
      overhead costs, data sources, charges or prices, sensitivity analysis,
      presentations of resource use and unit costs), enabling readers to judge the
      value of these studies. The 11 subjects covered by the economic evaluations are
      discussed. Many NHL treatments remain to be studied in economic evaluations.
      Future publications should report on the six methodological items in more detail,
      and preferably tackle them in the recommended way.

PMID- 15571471
TI  - Fulvestrant - a new treatment for postmenopausal women with hormone-sensitive
      advanced breast cancer.
AB  - Approximately 75% of breast tumours in postmenopausal women are positive for the
      oestrogen receptor (ER) and/or the progesterone receptor (PgR) and are,
      therefore, potential candidates for endocrine treatment. Fulvestrant is a new
      type of ER antagonist with no agonist effects and a novel mode of action; it
      binds, blocks and degrades the ER, leading to a reduction in cellular ER and,
      consequently, in PgR levels. This novel mode of action results in a lack of cross
      resistance with other commonly used endocrine treatments. In Phase III trials in
      postmenopausal women with advanced breast cancer progressing on prior anti
      oestrogen therapy, fulvestrant was at least as effective as the third-generation
      aromatase inhibitor, anastrozole, in terms of time to progression and objective
      response, and was associated with similar overall survival. In the first-line
      setting, fulvestrant showed similar efficacy to tamoxifen in patients with ER
      positive and/or PgR-positive disease. Efficacy in more heavily pretreated
      patients has also been demonstrated in the fulvestrant compassionate use
      programme. Fulvestrant is well tolerated, being associated with a significantly
      lower incidence of joint disorders compared with anastrozole, and a lower
      incidence of hot flushes compared with tamoxifen. Fulvestrant, therefore,
      provides clinicians with a useful additional treatment for hormone-sensitive
      advanced breast cancer in postmenopausal women. Ongoing trials will help to
      clarify the optimal position of fulvestrant in the endocrine treatment sequence
      for these patients.

PMID- 15571472
TI  - 17Beta-estradiol/levonorgestrel transdermal system for the management of the
      symptomatic menopausal woman.
AB  - Recent publications of the initial outcomes from the Women's Health Initiative
      (WHI) study of menopausal management have raised concerns over the safety of
      hormone therapy [1,2]. Every study, no matter how large or well conducted, has
      biases and limitations that preclude the ability to apply the outcomes to a
      larger group of individuals not specifically evaluated in the analysis. In
      particular, the hormonal arms of the WHI evaluated only a single dose of a daily
      oral regimen of conjugated equine oestrogen 0.625 mg [1,2], combined with
      medroxyprogesterone acetate 2.5 mg if the subject had a uterus [1]. The failure
      to evaluate non-oral regimens prevented the evaluation of hormone delivery
      systems that have been shown to provide similar symptom relief to oral regimens,
      but with a considerably different physiological impact. The once-weekly
      transdermal patch (Climara Pro releasing 17beta-estradiol 0.045 mg/day and
      levonorgestrel 0.015 mg/day has been shown to be highly effective in rapidly
      reducing the frequency and intensity of vasomotor symptoms and to significantly
      improve all categories in the quality of life Women's Health Questionnaire [3].
      In addition, this transdermal combination system was not associated with any
      cases of endometrial hyperplasia, adverse impacts on cholesterol or lipid values
      and was associated with an increasing rate of amenorrhoea over time [3]. The
      17beta-estradiol/levonorgestrel transdermal system is approved in the US for the
      treatment of moderate-to-severe vasomotor symptoms and the prevention and
      treatment of urogenital atrophy.

PMID- 15571473
TI  - Docosanol: a topical antiviral for herpes labialis.
AB  - Recurrent herpes labialis is a painful and potentially disfiguring infection
      affecting an estimated 40 million people in the US alone. The majority of
      recurrences are caused by herpes simplex virus type 1. Various oral and topical
      formulations of nucleoside analogues have demonstrated efficacy for this
      indication. Over-the-counter treatments are palliative in nature and do not
      reduce time to healing. Docosanol is a compound with a unique mechanism of action
      involving viral fusion inhibition. In randomised, clinical trials, a 10%
      docosanol cream formulation, initiated within 12 h of symptoms onset,
      demonstrated efficacy in reduction of time-to-healing compared with a
      polyethylene glycol control. Despite its potential to be a mild irritant, this
      novel antiviral was well-tolerated in clinical trials. Docosanol is the first
      topical antiviral approved for over-the-counter use in recurrent herpes labialis.

PMID- 15571474
TI  - Eplerenone in hypertension.
AB  - Appreciation of the role of aldosterone in cardiovascular and renal disease has
      increased in the last 50 years. The use of spironolactone was limited by adverse
      sexual effects, including gynaecomastia. Eplerenone is a newer aldosterone
      antagonist that is much more selective, with minimal affinity for progesterone
      and androgenic receptors; therefore, there are very few reports of adverse sexual
      effects. A review of published trials shows that eplerenone reduces blood
      pressure (BP) in a dose-dependent manner, from 50 to 200 mg/day, and to a similar
      degree as enalapril. It has an additive effect when given to patients
      inadequately controlled on an angiotensin-converting enzyme inhibitor or an
      angiotensin-receptor blocker. Eplerenone performs better than losartan in African
      American patients and lowers BP regardless of initial plasma renin activity. The
      risk of hyperkalaemia is low, similar to that of enalapril, and < 1% of patients
      have had to be withdrawn from studies because of elevated serum potassium levels.
      Eplerenone is an effective, well-tolerated antihypertensive agent that may be
      used alone or in conjunction with other agents; apart from the risk of
      hyperkalaemia, adverse effects are similar to placebo.

PMID- 15571475
TI  - Simvastatin: a review.
AB  - Simvastatin is a long-established hydroxy-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitor, first introduced in 1988. At the maximal recommended dose of
      80 mg/day, it produces an average reduction in low-density lipoprotein
      cholesterol (LDL-C) of 47%, accompanied by reductions in very LDL-C,
      triglycerides and apolipoprotein B, and a modest increase in high-density
      lipoprotein cholesterol. The only important, although rare, adverse effect of
      simvastatin is myopathy, an effect shared by all members of the class; when
      severe, this can take the form of rhabdomyolysis, which may lead to acute renal
      failure. The mechanism of the myopathy is not understood. The risk is increased
      by certain concomitant drugs, including gemfibrozil and potent inhibitors of
      cytochrome P450 3A4. Simvastatin has been studied in two large outcome trials,
      the Scandinavian Simvastatin Survival Study (4S), and the Heart Protection Study
      (HPS), both of which demonstrated strikingly beneficial effects on a variety of
      cardiovascular outcomes, with minimal adverse effects. 4S was the first study
      with a cholesterol-lowering agent to demonstrate an unequivocal reduction in all
      cause mortality (30%; p = 0.0003). HPS showed that the beneficial effects of
      simvastatin were obtainable in a broad array of patients with, or at high risk
      of, coronary heart disease (CHD) in categories previously little studied,
      including women, the elderly, patients with diabetes without known CHD, and,
      perhaps most importantly, patients with LDL-C well below the UK population
      average. Simvastatin has recently become available in many countries as a
      combination product with the cholesterol absorption inhibitor, ezetimibe. Because
      of its long record of safety and demonstrated ability to reduce cardiovascular
      risk, simvastatin has recently become available without a prescription in the UK
      at the 10 mg dosage level.

PMID- 15571476
TI  - Inhaled insulin: recent advances in the therapy of Type 1 and 2 diabetes.
AB  - There are promising data in the field of inhaled insulin. This article describes
      the current devices being developed for insulin delivery via inhalation.
      Encouraging advanced clinical data are available in Type 1 diabetes, where
      inhaled insulin is used in conjunction with basal insulin. Moreover, patients
      with Type 2 diabetes who have failed oral therapy show improved control when
      inhaled insulin therapy is initiated. Safety data show that cough is the most
      common side effect. Pulmonary function tests have shown some changes in carbon
      monoxide diffusion in the lung. Further studies are needed to clarify the
      significance of this finding. Inhaled insulin appears to be a non-invasive, well
      tolerated and -liked modality of treatment, with potential in both Type 1 and 2
      diabetes.

PMID- 15571477
TI  - Pentostatin - pharmacology, immunology, and clinical effects in graft-versus-host
      disease.
AB  - Pentostatin (deoxycoformycin), is one of a number of purine analogues. The drug
      was originally designed to mimic a form of severe combined immune deficiency,
      characterised by marked T lymphopenia but variable B cell function. Clinically,
      the drug has been used primarily to treat a rare type of leukaemia - hairy cell
      leukaemia. Recently, the drug has seen increasing attention as an
      immunosuppressant. This review will cover the basic pharmacology and
      immunological effects of pentostatin. The clinical use of this agent in
      prevention and treatment of graft-versus-host disease will be examined. Although
      many of these studies are ongoing, this agent has promise as a novel
      immunosuppressive agent with a new mechanism of action.

PMID- 15571478
TI  - Efficacy and safety of ivermectin and thiabendazole in the treatment of
      strongyloidiasis.
AB  - Treatment of strongyloidiasis has been traditionally based on thiabendazole,
      despite its frequent gastrointestinal side effects and failure to achieve
      eradication of the parasite from faeces in approximately 30% of cases. Ivermectin
      has been shown to be more effective for treating chronic uncomplicated
      strongyloidiasis. The efficacy and tolerability of these drugs in a series of
      patients treated from 1999 to 2002 at the Oliva Health Centre, Valencia, Spain,
      are reported. A total of 88 patients diagnosed of strongyloidiasis were treated
      using the following regimens: thiabendazole 25 mg/kg/12 h for 3 consecutive days
      in 31 patients; ivermectin 200 mug/kg as a single dose in 22 patients; and
      ivermectin 200 mug/kg for 2 consecutive days in 35 patients. The efficacy and
      side effects were recorded. A total of 65 patients were male, and 23 female. The
      mean age was 64 +/- 12 years. Of the patients, 44 had worked barefoot in rice
      fields. Among the 31 patients treated with thiabendazole, 25 (78%) met the
      criteria for cure (the absence of parasite in faeces after examination of three
      samples collected on alternate days), and 5 (16%) experienced side effects
      (asthenia, epigastralgia and disorientation). Of the 22 patients treated with
      ivermectin on a single day, 17 (77%) met the criteria for cure, and 2 (9%)
      reported side effects (dizziness, dyspepsia). Among the 35 patients treated with
      ivermectin on 2 consecutive days, 100% met the criteria for cure, and 0%
      experienced side effects. In chronic uncomplicated strongyloidiasis, a treatment
      regimen consisting of ivermectin 200 mug/kg for 2 consecutive days provided the
      best results with regard to efficacy and tolerability. When the eosinophilia
      continued after treatment, we observed a high percentage of not-cure rate (7 of 9
      patients, 77%).

PMID- 15571479
TI  - Which drug combination for colorectal cancer?
AB  - In Westernised countries, colorectal cancer (CRC) is second only to lung cancer
      as a cause of death from malignancy, with only 60% of patients alive at 5 years.
      In Stage II/III CRC, where the standard treatment is 5-fluorouracil (5
      FU)/leucovorin, a recent clinical trial has shown that with the addition of
      oxaliplatin, fewer patients have relapsed or died at 40 months follow-up. The
      benefit was more pronounced in patients with Stage III than II CRC, and the
      addition of oxaliplatin to 5-FU/leucovorin should be considered in Stage III CRC.
      In metastatic CRC, where the standard treatment is 5-FU/leucovorin/irinotecan, a
      recent clinical trial has shown that the addition of bevacizumab, a mAb, to
      vascular endothelial growth factor, prolonged progression-free and overall
      survival. Bevacizumab is likely to become part of the standard therapy for
      metastatic CRC.

PMID- 15571480
TI  - Emerging treatments in chronic hepatitis B.
AB  - Although the management of chronic hepatitis B has improved over the last decade,
      none of the available therapeutic agents, IFN-alpha, lamivudine and adefovir
      dipivoxil, can achieve sustained off-therapy responses in most cases. Therefore,
      several newer, mainly antiviral and immunomodulatory agents, are being evaluated.
      Pegylated IFN-alpha(2a) has been shown to be more effective than lamivudine or
      standard IFN-alpha monotherapy in achieving post-therapy biochemical and
      virological responses, and is expected to be licensed soon for the treatment of
      chronic hepatitis B. Newer antiviral agents, such as entecavir and telbivudine,
      appear to be quite effective initially, but their sustained off-therapy response
      rates remain unknown. The preliminary data of monotherapies with immunomodulatory
      agents, or of combination therapies, have been rather disappointing. Long-term
      maintenance treatment with antiviral agent(s) with good safety and tolerability
      profiles and low resistance rates appears to be the most realistic future
      therapeutic option for most chronic hepatitis B patients.

PMID- 15571481
TI  - Use of cytokines in infection.
AB  - Infectious disease remains an ever-growing health concern worldwide due to
      increasing antibiotic-resistant microbial strains, immune-compromised
      populations, international traffic and globalisation, and bioterrorism. There
      exists an urgent need to develop novel prophylactic and therapeutic strategies.
      In addition to classic antibiotic therapeutics, immune-modulatory molecules such
      as cytokines or their inhibitors represent a promising form of antimicrobial
      therapeutics or immune adjuvant used for the purpose of vaccination. These
      molecules, in the form of either recombinant protein or transgene, exert their
      antimicrobial effect by enhancing infectious agent-specific immune activation or
      memory development, or by dampening undesired inflammatory and immune responses
      resulting from infection and host defence mechanisms. In the last two decades, a
      number of cytokine therapy-based experimental and clinical trials have been
      conducted, and some of these efforts have led to the routine clinical use of
      cytokines. For instance, although IFNs have been used to treat hepatitis C with
      great success, many other cytokines are yet to be fully evaluated for their
      antimicrobial potential. This review discusses the biology and therapeutic
      potential of selected immune modulatory cytokines and their inhibitors, including
      granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating
      factor, IFN-gamma, IL-12 and TNF.

PMID- 15571482
TI  - Emerging therapies for herpes viral infections (types 1 - 8).
AB  - There are eight members of the herpesviridae family: herpes simplex virus-1 (HSV
      1), HSV-2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human
      herpes virus-6, human herpes virus-7 and human herpes virus-8. The diseases
      caused by viruses of the herpesviridae family are treated with and managed by
      systemic and topical antiviral therapies and immunomodulating drugs. Because
      these viruses establish a latent state in hosts, antiherpetic agents, such as
      nucleoside analogues, only control symptoms of disease or prevent outbreaks, and
      cannot cure the infections. There is a need for treatments that require less
      frequent dosing, can be taken even when lesions are more advanced than the first
      signs or symptoms, and can treat resistant strains of the viruses without the
      toxicities of existing therapies. Immunomodulating agents, such as resiquimod,
      can act on the viruses indirectly by inducing host production of cytokines, and
      can thereby reduce recurrences of herpes. The new helicase primase inhibitors,
      which are the first non-nucleoside antiviral compounds, are being investigated
      for treatment of HSV disease, including infections resistant to existing therapy.

PMID- 15571483
TI  - Promising treatments in development for food allergies.
AB  - Up to 6% of young children and 2% of adults suffer from food allergy. Among them
      many have IgE-mediated food allergy, a condition with potentially fatal allergic
      reactions. The only proven treatment is avoidance of the offending food, which
      can be identified using standardised allergic tests. However, several studies
      have addressed possible definite treatment options for food allergy.
      Immunotherapy, administered orally or by systemic injections, shows promising
      preliminary results, but these therapeutics are based on studies with
      insufficient scientific support, or are associated with a high risk of severe
      side effects. At present, no studies can support pharmacotherapy. However,
      promising results were recently published with anti-IgE antibodies in a human
      trial, and various approaches in a mouse model of food allergy (chinese herbal
      medicine, specific modulation of the T-cell response). Rapidly evolving findings
      might provide hope for a cure for food allergy in the near future.

PMID- 15571484
TI  - Statins: can the new generation make an impression?
AB  - Although large-scale statin trials have demonstrated significant reductions in
      cardiovascular risk, there are many patients who have a cardiovascular event
      despite receiving statin therapy. There is increasing evidence that larger
      reductions in low-density lipoprotein cholesterol (LDL-C) are associated with
      greater improvements in cardiovascular morbidity and mortality, which highlights
      the need for more efficacious statins. This article will review the lipid
      altering effects of two new statins, rosuvastatin and pitavastatin. Rosuvastatin
      represents an advance in the pharmacological and clinical properties of other
      available agents. The large LDL-C reductions observed with rosuvastatin, even at
      the start dose of 10 mg and in patients switched from other statins to
      rosuvastatin 10 mg, should help to improve goal attainment, while reducing the
      need for dose titration. The ability of rosuvastatin to improve other elements of
      the lipid profile, such as high-density lipoprotein cholesterol (HDL-C),
      triglycerides and non-HDL-C, may be of utility in patients with diabetes and the
      metabolic syndrome. Increases in HDL-C, along with the greater efficacy of
      rosuvastatin for reducing LDL-C and non-HDL-C, may obviate the need for
      combination therapy. Results of a number of outcome studies with rosuvastatin are
      expected over the next 5 years, which will contribute to the evidence base for
      statin therapy and cardiovascular disease prevention.

PMID- 15571485
TI  - Emerging drugs for narcolepsy.
AB  - Narcolepsy is characterised by excessive daytime sleepiness, usually associated
      with cataplexy, hypnagogic hallucinations, sleep paralysis and fragmented
      nocturnal sleep. Although uncommon, it results in significant disability. Most
      cases occur sporadically, but genetic factors probably form a susceptibility
      background on which unknown environmental triggers act. The hypocretin system is
      strongly implicated in the development of narcolepsy. Cerebrospinal fluid levels
      of hypocretin-1 are significantly reduced in narcoleptic subjects with cataplexy.
      Despite the advances in our understanding of narcolepsy, current therapy is
      primarily symptomatic. Stimulants (standard and novel) combat excessive daytime
      sleepiness. Antidepressants (tricyclics, dual-action or selective serotonin re
      uptake inhibitors) and sodium oxybate are anticataplexy agents. Hypnagogic
      hallucinations and sleep paralysis respond to antidepressants. Sodium oxybate
      consolidates sleep. Novel and experimental treatments include histamine
      antagonists, hypocretin agonists, slow-wave sleep enhancers, intravenous gamma
      globulin, tramadol and corticosteroids.

PMID- 15571486
TI  - New drugs for the treatment of attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neuropsychiatric disorder of childhood. Recent research indicates that ADHD most
      often persists into adolescence and adulthood, and is associated with impairments
      in academic, social and occupational functioning. The ADHD diagnosis is based on
      history and clinical examination. There are no objective laboratory measures for
      diagnosis. ADHD is largely heritable. Its underlying pathophysiology has been
      theorised to include dysregulation of inhibitory noradrenergic frontocortical
      activity on dopaminergic striatal structures. Evidence shows that ADHD is highly
      responsive to pharmacological treatments resulting in global functional
      improvements. Although pharmacotherapy is recognised as the most effective
      treatment, additional components to optimise ADHD management include proper
      educational placement, parent management training and social skills development.
      Central nervous system stimulants, specifically methylphenidate and amphetamine,
      remain first-line pharmacological treatments. Atomoxetine, a selective
      noradrenergic re-uptake inhibitor, is the first non-stimulant compound to receive
      FDA approval for paediatric and adult ADHD. Other medication classes, including
      alpha-agonist antihypertensives, tricyclic antidepressants, other antidepressants
      such as buproprion, and the wake-promoting agent modafinil, are prescribed in off
      label therapy. Ongoing development of new ADHD medications is expected to
      emphasise alternative and extended-release delivery systems and non-stimulant
      compounds.

PMID- 15571487
TI  - Antithrombotic trials in acute ischaemic stroke: a selective review.
AB  - Stroke is a common cause of morbidity and mortality throughout the US and the
      world. Given the highly disabling nature of this disease, it is important to
      provide acute therapy when indicated to improve individual outcomes. Recombinant
      tissue plasminogen activator (rt-PA) is, at present, the only approved drug for
      the treatment of acute strokes due to cerebral ischaemia. It can be given
      intravenously within a 3-h window of the onset of neurological deficits. Intra
      arterial administration of rt-PA within a 6-h window is performed at several
      academic centres in patients with middle cerebral and other intracranial artery
      occlusions based on results of a randomised clinical trial. Other thrombolytic
      agents are being studied in randomised trials. Although acute therapy of
      ischaemic stroke has received much attention since the approval of rt-PA, only a
      small percentage of individuals actually receive rt-PA. This article will review
      the main thrombolytic agents and the trials performed thus far, as well as
      examine some important ongoing trials. How administration of acute thrombolytic
      therapy may evolve in the future will also be addressed.

PMID- 15571488
TI  - Emerging treatments for soft tissue sarcoma of adults.
AB  - Soft tissue sarcomas are a heterogeneous group of malignancies arising from
      mesenchymal tissues. Patients can present with a localised tumour (primary or
      local recurrence) at different sites (e.g., extremity, abdomen) or metastatic
      disease, which may require different treatment strategies. Is the surgical
      resection of a localised sarcoma enough or is it better to give an additional
      treatment like adjuvant and/or preoperative radiotherapy and/or chemotherapy?
      Which chemotherapy should be selected in the first or second line situation? Do
      new treatment options exist, such as targeted therapies? This review provides
      answers to some of these questions. To decide on consecutive treatment steps, it
      is important to know as many relevant factors as possible at first presentation.
      Therefore, the first part of this review discusses the specific characteristics
      and prognostic factors of importance for treatment planning. A short summary of
      current therapy strategies and existing standards is then given. The main body of
      the review summarises information on new and emerging clinical compounds for
      patients with soft tissue sarcoma of adults, including recent developments of
      targeted therapy.

PMID- 15571489
TI  - Male hormonal contraception.
AB  - Although women have traditionally shouldered the responsibility of contraception,
      up to a third of couples worldwide employ a male form of contraception (e.g.,
      condoms or vasectomy). Some women are unable to use hormonal contraception;
      vasectomy is best considered irreversible; and long-term use of condoms is
      associated with a relatively high failure rate (pregnancy). Thus, a need exists
      for a safe, effective, reversible, well-tolerated male hormonal contraceptive
      agent. Two large multi-centre, multi-national trials sponsored by the World
      Health Organization in the 1990s showed that high-dosage exogenous testosterone
      provided contraceptive efficacy similar to existing female oral contraceptives.
      However, the supraphysiological dosages of testosterone used resulted in androgen
      related adverse effects such as weight gain and suppression of high-density
      lipoprotein cholesterol levels. Subsequent efforts have been directed at
      combining testosterone with other agents, such as progestogens or gonadotropin
      releasing hormone analogues, to decrease the dosage of testosterone (and thus
      androgen-related side effects) while achieving uniform azoospermia. This review
      discusses the latest developments in male hormonal contraception.

PMID- 15571490
TI  - Emerging drugs for sarcopenia: age-related muscle wasting.
AB  - Sarcopenia is the term widely used to describe the progressive loss of muscle
      mass with advancing age. Even before significant muscle wasting becomes apparent,
      ageing is associated with a slowing of movement and a gradual decline in muscle
      strength, factors that increase the risk of injury from sudden falls and the
      reliance of the frail elderly on assistance in accomplishing even basic tasks of
      independent living. Sarcopenia is recognised as one of the major public health
      problems now facing industrialised nations, and its effects are expected to place
      increasing demands on public healthcare systems worldwide. Although the effects
      of ageing on skeletal muscle are unlikely to be halted or reversed, the
      underlying mechanisms responsible for these deleterious changes present numerous
      targets for drug discovery with potential opportunities to attenuate muscle
      wasting, improve muscle function, and preserve functional independence. Very few
      drugs have been developed with sarcopenia specifically in mind. However, because
      many of the effects of ageing on skeletal muscle resemble those indicated in many
      neuromuscular disorders, drugs that target neurodegenerative diseases may also
      have important relevance for treating age-related muscle wasting and weakness.
      This review describes a selection of the emerging drugs that have been developed
      during the period 1997 - 2004, relevant to sarcopenia.

PMID- 15571491
TI  - Development of interferon-beta as a therapy for multiple sclerosis.
AB  - The introduction of interferon (IFN) therapy represents a milestone in multiple
      sclerosis (MS) treatment. This class of drugs is part of an evolving area of MS
      therapy that utilises immunomodulating agents to alter the immune processes
      thought to be integral to the development of MS. IFN-beta has been developed in
      three different formulations that have proven benefit in reducing exacerbations
      in relapsing-remitting MS. Two of the formulations consist of the naturally
      occurring amino acid sequence of IFN-beta and are referred to as IFN-beta(1a).
      One is delivered intramuscularly (IM IFN-beta(1a)), and the second form of IFN
      beta(1a) is delivered subcutaneously (SC IFN-beta(1a)). The third formulation of
      IFN-beta, known as IFN-beta(1b), consists of a modified amino acid sequence
      containing a cysteine to serine mutation at amino acid 17 and a deletion of the
      amino terminal methionine. This review describes the evolution of IFNs as
      therapeutics for MS.

PMID- 15571492
TI  - Inhibitory effect of palmitate on the mitochondrial NADH:ubiquinone
      oxidoreductase (complex I) as related to the active-de-active enzyme transition.
AB  - Palmitate rapidly and reversibly inhibits the uncoupled NADH oxidase activity
      catalysed by activated complex I in inside-out bovine heart submitochondrial
      particles (IC50 extrapolated to zero enzyme concentration is equal to 9 microM at
      25 degrees C, pH 8.0). The NADH:hexa-ammineruthenium reductase activity of
      complex I is insensitive to palmitate. Partial (approximately 50%) inhibition of
      the NADH:external quinone reductase activity is seen at saturating palmitate
      concentration and the residual activity is fully sensitive to piericidin. The
      uncoupled succinate oxidase activity is considerably less sensitive to palmitate.
      Only a slight stimulation of tightly coupled respiration with NADH as the
      substrate is seen at optimal palmitate concentrations, whereas complete relief of
      the respiratory control is observed with succinate as the substrate. Palmitate
      prevents the turnover-induced activation of the de-activated complex I (IC50
      extrapolated to zero enzyme concentration is equal to 3 microM at 25 degrees C,
      pH 8.0). The mode of action of palmitate on the NADH oxidase is qualitatively
      temperature-dependent. Rapid and reversible inhibition of the complex I catalytic
      activity and its de-active to active state transition are seen at 25 degrees C,
      whereas the time-dependent irreversible inactivation of the NADH oxidase proceeds
      at 37 degrees C. Palmitate drastically increases the rate of spontaneous de
      activation of complex I in the absence of NADH. Taken together, these results
      suggest that free fatty acids act as specific complex I-directed inhibitors; at a
      physiologically relevant temperature (37 degrees C), their inhibitory effects on
      mitochondrial NADH oxidation is due to perturbation of the pseudo-reversible
      active-de-active complex I transition.

PMID- 15571493
TI  - The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel
      dimeric structure in solution via its leucine-zipper-like domain.
AB  - HIV-1 Vpr is a highly conserved accessory protein that is involved in many
      functions of the virus life cycle. Vpr facilitates the entry of the HIV pre
      integration complex through the nuclear pore, induces G2 cell cycle arrest,
      regulates cell apoptosis, increases transcription from the long terminal repeat
      and enhances viral replication. Vpr contains a Leu/Ile-rich domain (amino acids
      60-81) in its C-terminal part, which is critical for dimerization. The sequence
      comprising residues 52-96 is implicated in properties of the protein such as DNA
      interaction and apoptosis via interaction with the adenine nucleotide
      translocator. To understand the specific interactions of Vpr-(52-96), the ability
      of this peptide to dimerize via a leucine-zipper mechanism has been investigated,
      by NMR and fluorescence spectroscopy. In contrast with results from a study
      performed in the presence of trifluoroethanol, our results, obtained in 30% (v/v)
      [2H]acetonitrile, show that Vpr-(52-96) in solution still forms an a-helix
      spanning residues 53-75, but dimerizes in an antiparallel orientation, through
      hydrophobic interactions between leucine and isoleucine residues and stacking
      between His71 and Trp54. Moreover, to demonstrate the physiological relevance of
      the dimer structure, fluorescence spectroscopy experiments have been performed in
      a Mes buffer, which confirmed the formation of the dimer in aqueous solution and
      highlighted the spatial proximity between Trp54 and His71. Surprisingly, the
      leucine-zipper structure shown in the present work for Vpr-(52-96) mimics the
      structure of full-length Vpr-(1-96), and this could explain why some of the
      properties of Vpr-(52-96) and Vpr-(1-96) are identical, while some are even
      enhanced for Vpr-(52-96), particularly in the case of DNA transfection
      experiments.

PMID- 15571494
TI  - Therapy of cutaneous human Papillomavirus infections.
AB  - Human Papillomaviruses (HPV) are double-stranded DNA viruses, which result in a
      variety of clinical manifestations according to type. The most common cutaneous
      lesions include warts located on the skin and genitalia. Because there is
      currently no cure for HPV infection, treatment focuses on the alleviation of
      signs and symptoms. Unfortunately, therapy has not been proved to affect
      transmissibility. Traditional treatment modalities have focused on the
      destruction of infected tissue through a variety of techniques. These include
      podophyllin resin, podophyllotoxin, salicylic acid, trichloroacetic acid,
      bichloroacetic acid, cryotherapy, laser, and surgical techniques. None of these
      modalities have been proved to be superior. More recently, immunomodulatory
      compounds with antiviral properties have demonstrated superior efficacy with
      clearance rates up to 77% and low recurrence rates. Most importantly, clinical
      trials of vaccines to prevent acquisition of oncogenic HPV are demonstrating
      marked safety and efficacy.

PMID- 15571495
TI  - Therapy of HIV infection.
AB  - HIV is a devastating disease caused by the human immunodeficiency virus. Symptoms
      of illness can manifest in every organ system, including the skin. Although there
      is no definitive cure, the creation of antiretroviral drugs and aggressive
      treatment regimens have dramatically altered disease morbidity and mortality.
      However, the precise drug selection is often difficult and intimidating given the
      sheer abundance of drug therapies available. In this article, the HIV disease
      course is reviewed and different classes of antiretroviral medications are
      presented with emphasis on initial drug regimens, potential adverse effects,
      particularly those of dermatologic nature, possible drug interactions, patient
      compliance, and the emergence of drug resistance.

PMID- 15571496
TI  - Therapy of other viral infections: herpes to hepatitis.
AB  - Over the past several years, there has been an increase in knowledge pertaining
      to the diagnosis and management strategies for the herpes family (Types 1-8), the
      pox viruses, mumps, measles, rubella, and parvovirus B19 as well as the viral
      etiologies of hepatitis. Various antiviral treatments, such as nucleoside analogs
      and interferon therapy, have been available to reduce the signs and symptoms of
      these common viral infections. This article summarizes the preferred treatment
      strategies to be employed for each of the viruses for reducing severity,
      duration, recurrences (notably in the herpes family), transmission rates, as well
      as preventive alternatives. The majority of the therapeutic options attenuate the
      course of disease. Treatment decisions are driven by knowledge of the natural
      history and often are tailored to incorporate clinical circumstances for
      individual patients. Promotion of community awareness and the development of
      vaccines should be emphasized in the battle against these common viruses,
      particularly the herpes simplex viruses, the pox viruses, and hepatitis B.

PMID- 15571497
TI  - Therapy of nontuberculous mycobacterial infections.
AB  - Mycobacterial infections are increasing in incidence worldwide, partly as a
      result of the increase in immunocompromised individuals. They cause a large
      number of cutaneous infections with a broad array of manifestations. Because of
      their diverse manifestations and sometimes fastidious nature, infections with
      mycobacteria are often misdiagnosed, leading to delay in and sometimes failure of
      therapy. In addition, many mycobacteria display both in vitro and in vivo drug
      resistance to antimicrobial agents. Early recognition of affected patients,
      initiation of appropriate antimicrobial therapy based on current guidelines, and
      tailoring of therapy after susceptibility testing is available are therefore
      essential to the successful treatment of mycobacterial infections.

PMID- 15571498
TI  - Treatment and prevention of rickettsial and ehrlichial infections.
AB  - Rickettsial and ehrlichial infections are both carried by arthropod vectors. Both
      Rickettsia and Ehrlichia are small intracellular gram-negative coccobacilli.
      Clinical manifestations of Rickettsia range from spotted fevers to various forms
      of typhus. Human ehrlichiosis can present as monocytic ehrlichiosis or
      granulocytic anaplasmosis. Prevention is by avoidance of the responsible vectors.
      Therapy is usually with doxycycline, but chloramphenicol can also be used.

PMID- 15571499
TI  - Therapy of other bacterial infections.
AB  - Cutaneous bacterial disease continues to account for a significant proportion of
      clinical visits. The continuing emergence of strains that are resistant to
      available antibacterial agents creates a challenge for dermatologists, who need
      to keep abreast of current treatment strategies. In this article, antibacterial
      regimens are presented for skin infections caused by organisms such as
      Staphylococcus, Streptococcus, Pseudomonas, Neisseria, Haemophilus ducreyi,
      Treponema pallidum, Bacillus anthracis, Yersinia pestis, Pasteurella multocida,
      Vibrio vulnificus, Actinomyces, and Nocardia.

PMID- 15571500
TI  - Treatment of protozoan infections.
AB  - Protozoan infections can have a variety of different cutaneous manifestations in
      addition to systemic signs and symptoms of disease. Recognition and diagnosis can
      be difficult, as additional laboratory tests, in addition to biopsies, may be
      required. Treatment options for different protozoa vary and resolution of disease
      may be refractory despite lengthy treatment courses. An overview of cutaneous
      manifestations, diagnosis, and treatment regimen of amebiasis, leishmaniasis,
      trypanosomiasis, and toxoplasmosis is outlined in this article.

PMID- 15571501
TI  - Therapy of common superficial fungal infections.
AB  - Superficial fungal infections are common, especially onychomycosis,
      dermatophytoses, and superficial Candida infections. Most superficial fungal
      infections are treated with topical antifungal agents unless the infection covers
      an extensive area or is resistant to initial therapy. Onychomycosis often
      requires systemic therapy with griseofulvin, itraconazole, or terbinafine. The
      objective of this review is to provide the practicing dermatologist with the
      recommended available therapy for the treatment of common superficial fungal
      infections.

PMID- 15571502
TI  - Subcutaneous fungal infections.
AB  - Subcutaneous mycoses are caused by a variety of mostly tropical organisms,
      usually when they are implanted into the dermis or the subcutaneous tissue. They
      rarely disseminate or become systemic. Sporotrichosis, mycetoma, and
      chromoblastomycosis are more common subcutaneous mycoses than are
      rhinosporidiosis, zygomycosis, pheohyphomycosis, and lobomycosis.

PMID- 15571503
TI  - Therapy of systemic fungal infections.
AB  - The incidence of both community-acquired and nosocomial fungal infections has
      significantly increased over the past several decades. The major factors for this
      increase are a heightened use of antibiotics, a growing population of the elderly
      and of immunocompromised patients as a result of HIV, cancer, and organ
      transplantation. In this article, we will review the indications, efficacy, and
      safety of the polyenes, imidazoles, triazoles, and other systemic antifungals in
      development that are used for systemic fungal infections.

PMID- 15571505
TI  - The mechanism of neuroprotection by topiramate in an animal model of epilepsy.
AB  - PURPOSE: For the antiepileptic drug (AED) topiramate (TPM), neuroprotective
      effects have been reported in models of focal cerebral ischemia and experimental
      status epilepticus, but the putative mechanism of action has remained elusive.
      METHODS: We studied the effects of TPM on mitochondrial function in the
      pilocarpine rat model of chronic epilepsy and in isolated mitochondria from rat
      brain. RESULTS: TPM treatment in status epilepticus at doses ranging from 20 to
      100 mg/kg considerably improved the survival of rats and improved CA1 and CA3
      pyramidal cell survival in a dose-dependent manner. This treatment increased the
      activity of mitochondrial respiratory chain complex I in the CA1 and CA3
      pyramidal subfields and resulted in lower seizure frequencies in chronic
      epileptic rats. In vitro investigations of the action of TPM on isolated rat
      brain mitochondria ruled out any direct effects of the drug on mitochondrial
      oxidative phosphorylation but revealed a protective effect on hippocampal
      mitochondria against an external calcium challenge. This can explain its observed
      neuroprotective action in the concentration range tested. The in vitro effects of
      TPM on the calcium handling of isolated brain mitochondria was found to be
      comparable to the action of cyclosporin A. CONCLUSIONS: The neuroprotective
      action of TPM seems to be directly related to its inhibitory effect on the
      mitochondrial permeability transition pore.

PMID- 15571506
TI  - Striking differences in individual anticonvulsant response to phenobarbital in
      rats with spontaneous seizures after status epilepticus.
AB  - PURPOSE: More than one third of patients with epilepsy have inadequate control of
      seizures with drug therapy, but mechanisms of intractability are largely unknown.
      Because of this large number of pharmacoresistant patients with epilepsy, the
      existing process of antiepileptic drug (AED) discovery and development must be
      reevaluated with a focus on preclinical models of therapy-resistant epilepsy
      syndromes such as mesial temporal lobe epilepsy (TLE). However, although various
      rodent models of TLE are available, the pharmacoresponsiveness of most models is
      not well known. In the present study, we used a post-status epilepticus model of
      TLE to examine whether rats with spontaneous recurrent seizures (SRSs) differ in
      their individual responses to phenobarbital (PB). METHODS: Status epilepticus was
      induced in Sprague-Dawley rats by prolonged electrical stimulation of the
      basolateral amygdala. Once the rats had developed SRSs, seizure frequency and
      severity were determined by continuous EEG/video recording over a 6-week period
      (i.e., a predrug control period of 2 weeks, followed by PB treatment for 2 weeks,
      and a postdrug control period of 2 weeks). PB was administered twice daily at
      maximal tolerated doses. RESULTS: Analysis of plasma drug concentrations showed
      that drug concentrations within the therapeutic range (10-40 microg/ml) were
      maintained in all rats throughout the period of treatment. In six (55%) of 11
      rats, complete control of seizures was achieved, and another rat exhibited a >90%
      reduction of seizure frequency. These seven rats were considered responders. The
      remaining four (36%) rats showed either no response at all (n=3) or only moderate
      reduction in seizure frequency and were therefore considered nonresponders.
      Plasma drug concentrations did not differ between these two groups of rats.
      CONCLUSIONS: These data demonstrate that, similar to patients with epilepsy, rats
      with SRSs markedly differ in their individual responses to AED treatment.
      Pharmacoresistant rats selected by prolonged drug treatment from groups of rats
      with SRSs may provide a unique model to study mechanisms of pharmacoresistance
      and to identify novel AEDs for treating seizures of patients currently not
      controlled with existing therapies.

PMID- 15571507
TI  - Neurotoxicity induced by antiepileptic drugs in cultured hippocampal neurons: a
      comparative study between carbamazepine, oxcarbazepine, and two new putative
      antiepileptic drugs, BIA 2-024 and BIA 2-093.
AB  - PURPOSE: Newly designed antiepileptic drugs (AEDs) are being evaluated for their
      efficacy in preventing seizures and for their toxic profiles. We investigated and
      compared the toxic effects of two dibenz[b,f]azepine derivatives with
      anticonvulsant activity, 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f]azepine-5
      carboxamide (BIA2-024) and (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]
      azepine-5-carboxamide (BIA2-093), with the structurally related compounds
      carbamazepine (CBZ) and oxcarbazepine (OXC), both in current use for the
      treatment of epilepsy. METHODS: Primary rat hippocampal neurons were used to
      evaluate neuronal morphology and biochemical changes induced by the AEDs used in
      this study. Immunocytochemical staining against MAP-2 was used to evaluate
      neuronal morphology. Reactive oxygen species (ROS) and changes in mitochondrial
      membrane potential (Psim) were measured by fluorescence techniques. Intracellular
      adenosine triphosphate (ATP) levels were quantified by high-performance liquid
      chromatography (HPLC). RESULTS: Hippocampal neurons treated for 24 h with CBZ or
      OXC (300 microM) showed degeneration and swelling of neurites, but this effect
      was not observed in neurons treated with BIA 2-024 or BIA 2-093 (300 microM). ROS
      production also was increased in neurons treated with OXC, but not in neurons
      treated with the other AEDs. ATP levels were significantly decreased only in
      neurons treated with OXC, although the energy charge was not altered.
      Furthermore, OXC led to a decrease of Psim. CONCLUSIONS: In all parameters
      assayed, OXC was more toxic than the other AEDs used. Because the new putative
      AEDs have previously been shown to have an efficacy in preventing seizures
      similar to that of CBZ and OXC, and are less toxic to neuronal cells, they may be
      considered as alternatives to the current available therapies for the treatment
      of epilepsy.

PMID- 15571508
TI  - Expression and cellular distribution of major vault protein: a putative marker
      for pharmacoresistance in a rat model for temporal lobe epilepsy.
AB  - PURPOSE: Because drug transporters might play a role in the development of
      multidrug resistance (MDR), we investigated the expression of a vesicular drug
      transporter, the major vault protein (MVP), in a rat model for temporal lobe
      epilepsy. METHODS: By using real-time polymerase chain reaction (PCR) analysis
      and immunocytochemistry, we quantified MVP mRNA and protein from the dentate
      gyrus (DG) and parahippocampal cortex (PHC) taken from EEG-monitored rats at 1
      week after electrically induced status epilepticus (SE) and at 5-9 months after
      SE, when rats exhibit spontaneous seizures. RESULTS: Within 1 week after SE, MVP
      mRNA levels increased in both DG and PHC compared with those in controls. In
      chronic epileptic rats, MVP mRNA was still significantly upregulated in the PHC,
      whereas in the DG, the expression returned to control levels. MVP protein
      increased within 1 day after SE in reactive microglial cells within most limbic
      regions; the hippocampus showed the highest expression at 1 week after SE. In
      chronic epileptic rats, MVP protein expression was largely decreased in most
      brain regions, but it was still high, especially in the piriform cortex. The
      occurrence of SE was a prerequisite for increased MVP expression, because no
      increase was found in electrically stimulated rats that did not exhibit SE.
      CONCLUSIONS: MVP expression is upregulated in chronic epileptic rats and may
      contribute to the development of pharmacoresistance.

PMID- 15571509
TI  - Altered expression of neurotransmitter-receptor subunit and uptake site mRNAs in
      hemimegalencephaly.
AB  - PURPOSE: Hemimegalencephaly (HMEG) is characterized by unilateral hemispheric
      enlargement and severe cytoarchitectural abnormalities that are highly associated
      with intractable epilepsy. No studies have defined alterations in
      neurotransmitter-receptor subunit gene expression in HMEG. We hypothesize that a
      differential expression of excitatory amino acid and gamma-aminobutyric acid
      (GABA)A-receptor subunit messenger RNAs (mRNAs) exists in HMEG. METHODS: The
      expression of mRNAs encoding 20 neurotransmitter-receptor subunits, synthetic
      enzymes, and uptake sites as well as select additional candidate genes was
      defined in HMEG samples (n=8) compared with homotopic control cortex specimens by
      using targeted complementary DNA (cDNA) arrays. Expression of GLT-1 (a glial
      glutamate transporter), EAAC-1 (neuronal glutamate transporter), and NMDA2B was
      corroborated by immunohistochemical, Western, and ligand-binding assays. RESULTS:
      Differential expression of 11 neurotransmitter-related mRNAs was demonstrated in
      HMEG compared with control cortex. For example, expression of GLT-1 and GluR6
      mRNAs was enhanced, whereas diminished expression of the neuronal glutamate
      transporter EAAC-1, GABAAalpha2, GABAAgamma2, GABAAgamma3, NMDA2B, GluR1, GluR2,
      GluR4, and GluR5 subunits occurred. Reduced NMDA2B subunit mRNA expression in
      HMEG was confirmed by receptor ligand-binding assays by using the NMDA2B-receptor
      antagonist ifenprodil, which revealed barely detectable levels of NMDA2B binding
      compared with that in control cortex. CONCLUSIONS: Selective alterations occur in
      distinct neurotransmitter-receptor and -uptake sites in HMEG. Differential
      expression of neurotransmitter-receptor and -uptake sites in HMEG may contribute
      to epileptogenesis in HMEG.

PMID- 15571510
TI  - Abnormal cortical cells and astrocytomas in the Eker rat model of tuberous
      sclerosis complex.
AB  - PURPOSE: In patients with tuberous sclerosis complex (TSC), a wide range of
      neurologic abnormalities develop, including mental retardation and seizures.
      Brains from TSC patients are characterized by the presence of cortical tubers,
      large dysmorphic neurons, and abnormal cytomegalic cells. Although analysis of
      human TSC brain samples led to the identification of these abnormal cell types,
      very little is known about how these cells function. In an effort to model TSC
      associated CNS abnormalities (and ultimately to analyze the electrophysiologic
      properties of abnormal cells), we examined Eker rats carrying a Tsc2 mutation.
      Anatomic studies, including standard histologic stains and immunocytochemistry,
      were performed on young Eker rats exposed to a carcinogen in utero or aged
      untreated Eker rats (18-24 months old). METHODS: Pregnant TSC2+/- females were
      injected once a day with hydroquinone (HQ), and offspring were killed at
      postnatal day P14 or P28. Coronal tissue sections throughout the CNS were
      prepared and stained for cresyl violet. In separate studies, brains of old
      untreated Eker rats were sectioned for anatomic analysis by using standard
      immunohistochemical techniques. RESULTS: Tissue sections stained with cresyl
      violet did not reveal any gross differences between HQ-treated Eker (Tsc2Ek/+)
      rats and siblings (Tsc2+/+). However, two classes of abnormal giant cells were
      observed in brain sections from untreated aged Eker rats: (a) large dysmorphic
      pyramid-like cells immunoreactive for NeuN, tuberin, and EAAC-1 in layers IV-VI;
      and (b) abnormal cytomegalic cells immunoreactive for glial fibrillary acidic
      protein (GFAP), vimentin, and nestin in deep cortical layers or along the white
      matter. In addition, large subependymal astrocytomas were observed in four
      animals. CONCLUSIONS: Our data suggest that cortical tuber formation in Eker rats
      is a rare event and that prenatal exposure to a nongenotoxic carcinogen such as
      HQ is not sufficient to induce tuber formation. However, with advanced age, an
      increased likelihood of astrocytoma formation and the emergence of dysmorphic
      neurons and cytomegalic cells in the Eker rat brain might exist; each of these
      abnormalities mimics those seen clinically and could contribute to neurologic
      problems associated with TSC. Further analysis of this rodent model may be
      warranted.

PMID- 15571511
TI  - Progestins in the hippocampus of female rats have antiseizure effects in a
      pentylenetetrazole seizure model.
AB  - PURPOSE: Progestins can have profound effects on seizure processes. However, the
      effects and mechanisms of progestins to modulate seizures have not been
      systematically investigated. The present studies were designed to characterize
      the effects of progestins to modulate pentylenetetrazole (PTZ)-induced seizures
      in female rats. METHODS: In Experiment 1, ictal activity and plasma and
      hippocampal progesterone (P) and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha
      THP) levels of proestrous rats were compared with those of diestrous and
      ovariectomized (ovx) rats. Experiments 2 and 3 examined effects of ovx and
      replacement with vehicle, P, or 3alpha,5alpha-THP, systemically (Experiment 2) or
      to the hippocampus (Experiment 3) on seizures and plasma and hippocampal P and
      3alpha,5alpha-THP concentrations. RESULTS: Proestrous rats had reduced ictal
      activity and increased levels of P and 3alpha,5alpha-THP in plasma and
      hippocampus compared with diestrous or ovx rats (Experiment 1). Rats administered
      systemic P or 3alpha,5alpha-THP had significantly reduced ictal activity and
      increased plasma and hippocampal P and 3alpha,5alpha-THP levels compared with
      vehicle-administered rats (Experiment 2). Administration of P or 3alpha,5alpha
      THP to the hippocampus of ovx rats significantly reduced seizure activity and
      increased hippocampal, but not plasma, levels of P and 3alpha,5alpha-THP compared
      with vehicle administration (Experiment 3). CONCLUSIONS: Together, these data
      suggest that P can have antiseizure effects, and these effects may be due in part
      to actions of its metabolite, 3alpha,5alpha-THP, in the hippocampus.

PMID- 15571512
TI  - Seizures in the developing brain cause adverse long-term effects on spatial
      learning and anxiety.
AB  - PURPOSE: Seizures in the developing brain cause less macroscopic structural
      damage than do seizures in adulthood, but accumulating evidence shows that
      seizures early in life can be associated with persistent behavioral and cognitive
      impairments. We previously showed that long-term spatial memory in the eight-arm
      radial-arm maze was impaired in rats that experienced a single episode of kainic
      acid (KA)-induced status epilepticus during early development (postnatal days (P)
      1-14). Here we extend those findings by using a set of behavioral paradigms that
      are sensitive to additional aspects of learning and behavior. METHODS: On P1, P7,
      P14, or P24, rats underwent status epilepticus induced by intraperitoneal
      injections of age-specific doses of KA. In adulthood (P90-P100), the behavioral
      performance of these rats was compared with that of control rats that did not
      receive KA. A modified version of the radial-arm maze was used to assess short
      term spatial memory; the Morris water maze was used to evaluate long-term spatial
      memory and retrieval; and the elevated plus maze was used to determine anxiety.
      RESULTS: Compared with controls, rats with KA seizures at each tested age had
      impaired short-term spatial memory in the radial-arm maze (longer latency to
      criterion and more reference errors), deficient long-term spatial learning and
      retrieval in the water maze (longer escape latencies and memory for platform
      location), and a greater degree of anxiety in the elevated plus maze (greater
      time spent in open arms). CONCLUSIONS: These findings provide additional support
      for the concept that seizures early in life may be followed by life-long
      impairment of certain cognitive and behavioral functions. These results may have
      clinical implications, favoring early and aggressive control of seizures during
      development.

PMID- 15571513
TI  - Heat shock protein-27 is upregulated in the temporal cortex of patients with
      epilepsy.
AB  - PURPOSE: Heat shock protein-27 (HSP-27) belongs to the group of small heat shock
      proteins that become induced in response to various pathologic conditions. HSP-27
      has been shown to protect cells and subcellular structures, particularly
      mitochondria, and serves as a carrier for estradiol. It is a reliable marker for
      tissues affected by oxidative stress. Oxidative stress and related cellular
      defence mechanisms are currently thought to play a major role during
      experimentally induced epileptic neuropathology. We addressed the question
      whether HSP-27 becomes induced in the neocortex resected from patients with
      pharmacoresistant epilepsy. METHODS: Human epileptic temporal neocortex was
      obtained during neurosurgery, and control tissue was obtained at autopsy from
      subjects without known neurologic diseases. The tissues were either frozen for
      Western blot analysis or fixed in Zamboni's fixative for the topographic
      detection of HSP-27 at the cellular level by means of immunohistochemistry.
      RESULTS: HSP-27 was highly expressed in all epilepsy specimens and in the cortex
      of a patient who died in the final stage of multiple sclerosis (positive
      control), whereas only low amounts of HSP-27 were detectable in control brains.
      In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood
      vessels. The intracortical distribution patterns varied strongly among the
      epilepsy specimens. CONCLUSIONS: These results demonstrate that HSP-27 becomes
      induced in response to epileptic pathology. Although the functional aspects of
      HSP-27 induction during human epilepsy have yet to be elucidated, it can be
      concluded that HSP-27 is a marker for cortical regions in which a stress response
      has been caused by seizures.

PMID- 15571514
TI  - Effect of an external responsive neurostimulator on seizures and electrographic
      discharges during subdural electrode monitoring.
AB  - PURPOSE: Approved neural-stimulation therapies for epilepsy use prolonged
      intermittent stimulation paradigms with no ability to respond automatically to
      seizures. METHODS: A responsive neurostimulator that can automatically analyze
      electrocortical potentials, detect electrographic seizures, and rapidly deliver
      targeted electrical stimuli to suppress them was evaluated in an open multicenter
      trial in 50 patients, 40 of whom received responsive cortical stimulation via
      subdural electrodes implanted for epilepsy surgery evaluations. RESULTS: Four
      patients, ages 15 to 28 years, monitored at three institutions, with clinical and
      electrographic response to neurostimulation, are described. Electrographic
      seizures were altered and suppressed in these patients during trials of
      neurostimulation lasting < or =68 h, with no major side effects. In one patient,
      stimulation appeared also to improve the baseline EEG. CONCLUSIONS: Responsive
      cortical neurostimulation may be a safe and effective treatment for partial
      epilepsy. This information was derived from a small group of patients in an
      observation study. A double-blind, controlled Food and Drug Administration (FDA)
      approved study of a permanently implanted responsive neurostimulation system to
      treat medically refractory partial seizures is under way.

PMID- 15571515
TI  - Are "generalized" seizures truly generalized? Evidence of localized mesial
      frontal and frontopolar discharges in absence.
AB  - PURPOSE: To determine whether specific regions of cerebral cortex are activated
      at the onset and during the propagation of absence seizures. METHODS: Twenty-five
      absence seizures were recorded in five subjects (all women; age 19-58 years) with
      primary generalized epilepsy. To improve spatial resolution, all studies were
      performed with dense-array, 256-channel scalp EEG. Source analysis was conducted
      with equivalent dipole (BESA) and smoothed linear inverse (LORETA) methods.
      Analyses were applied to the spike components of each spike-wave burst in each
      seizure, with sources visualized with standard brain models. RESULTS: For each
      patient, the major findings were apparent on inspection of the scalp EEG maps and
      waveforms, and the two methods of source analysis gave generally convergent
      results. The onset of seizures was typically associated with activation of
      discrete, often unilateral areas of dorsolateral frontal or orbital frontal lobe.
      Consistently across all seizures, the negative slow wave was maximal over frontal
      cortex, and the spike that appeared to follow the slow wave was highly localized
      over frontopolar regions of orbital frontal lobe. In addition, sources in
      dorsomedial frontal cortex were engaged for each spike-wave cycle. Although each
      patient showed unique features, the absence seizures of all patients showed
      rapid, stereotyped evolution to engage both mesial frontal and orbital frontal
      cortex sources during the repeating cycles of spike-wave activity. CONCLUSIONS:
      These data suggest that absence seizures are not truly "generalized," with
      immediate global cortical involvement, but rather involve selective cortical
      networks, including orbital frontal and mesial frontal regions, in the
      propagation of ictal discharges.

PMID- 15571516
TI  - Identification of the epileptogenic lobe in neocortical epilepsy with proton MR
      spectroscopic imaging.
AB  - PURPOSE: The aim of this study was to evaluate the usefulness of multislice
      magnetic resonance spectroscopic imaging (MRSI) in combination with tissue
      segmentation for the identification of the epileptogenic focus in neocortical
      epilepsy (NE). METHODS: Twenty patients with NE (10 with MRI-visible
      malformations, 10 with normal MRI) and 19 controls were studied. In controls, N
      acetylaspartate NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed
      as a function of white matter, and thresholds were determined by calculating the
      95% prediction intervals (PIs) for NAA/Cr and NAA/Cho. Voxels with NAA/Cr or
      NAA/Cho values less than the 95% PI were defined as "pathological." Z-scores were
      calculated. Depending on the magnitude of those z-scores, we used two different
      methods (score-localization or forced-localization) to identify in a given
      subject the lobe with the highest percentage of pathological voxels, which was
      supposed to represent the epileptogenic lobe. RESULTS: MRSI correctly identified
      the lobe containing the epileptogenic focus as defined by EEG in 65% of the NE
      patients. MRSI localization of the focus was correct in 70% of the patients with
      an MRI-visible malformation and in 60% of the patients with normal MRI. Of the
      patients, 15% had metabolically abnormal brain regions outside the epileptogenic
      lobe, and 35% of the patients had evidence for secondary hippocampal damage.
      CONCLUSIONS: MRSI may be helpful for the identification of the epileptogenic
      focus in NE patients, even in NE with normal MRI.

PMID- 15571517
TI  - Semiologic and electrophysiologic correlations in temporal lobe seizure subtypes.
AB  - PURPOSE: The International League Against Epilepsy (ILAE) classification
      distinguishes medial and neocortical temporal lobe epilepsies. Among other
      criteria, this classification relies on the identification of two different
      electroclinical patterns, those of medial (limbic) and lateral (neocortical)
      temporal lobe seizures, depending on the structure initially involved in the
      seizure activity. Recent electrophysiologic studies have now identified seizures
      in which medial and neocortical structures are both involved at seizure onset.
      The purpose of the study was therefore to study the correlations of ictal
      semiology with the spatiotemporal pattern of discharge in temporal lobe seizures.
      METHODS: The 187 stereoelectroencephalography-recorded seizures from 55 patients
      were analyzed. Patients were classified into three groups according to
      electrophysiologic findings: medial (M; seizure onset limited to medial
      structures, n=24), lateral (L; seizure onset limited to lateral structures,
      n=13), and medial-lateral (ML; seizure onset involving both medial and lateral
      structures, n=18). Clinical findings were compared between groups. RESULTS:
      Initial epigastric sensation, initial fear, delayed oroalimentary and elementary
      upper limb automatisms, delayed loss of contact, long seizure duration, and
      absent or rare secondary generalizations were associated with M seizures. Initial
      auditory illusion or hallucination, initial loss of contact, shorter duration of
      seizures, and more frequent generalizations were associated with L seizures.
      Initial epigastric sensation, initial loss of contact, early oroalimentary and
      verbal automatisms, and long duration of seizures were associated with ML
      seizures. CONCLUSIONS: Although the syndrome of mesial temporal epilepsy is now
      relatively well defined, our findings support the idea that the organization of
      temporal lobe seizures may be complex and that different patterns exist. We
      demonstrate three distinct patterns, characterized by both semiologic and
      electrophysiologic features. This distinction may help to define better the
      epileptogenic zone and the subsequent surgical procedure.

PMID- 15571518
TI  - Benign focal seizures of adolescence: a prospective study.
AB  - PURPOSE: To characterize the clinical and EEG findings and evolution of the
      syndrome of benign focal seizures of adolescence (BFSA), as described by Loiseau
      et al. METHODS: A prospective study was performed in adolescents with normal
      clinical and neurologic examinations and normal neuroradiologic studies who had
      focal seizures that occurred isolated or in a cluster, with or without secondary
      generalization in the first 24 to 48 h after onset. None of the patients was
      treated with antiepileptic drugs (AEDs). RESULTS: Between January 1996 and
      January 2002, 15 patients with BFSA were enrolled in the study. Median age at
      onset of BFSA was 14 years. Thirteen patients had focal sensory or motor
      seizures. In two patients, the ictal manifestation was motion arrest associated
      with oral automatisms. Eight of them evolved to generalized tonic-clonic
      seizures. Thirteen patients had seizures only when awake, and the other two, both
      when awake and during sleep. Repeated interictal EEGs were normal, but in four of
      the patients who had seizures in a cluster, we were able to record an EEG within
      8 h after seizure onset. Two of these four patients had focal seizures, and their
      waking EEG showed focal centroparietal theta activities. The other two patients
      had secondarily generalized seizures, and their waking EEG showed bilateral theta
      activities instead. Prognosis was excellent. CONCLUSIONS: BFSA is a well-defined
      seizure syndrome, recognizable by clinical and EEG features, as described by
      Loiseau et al. In teenagers with these electroclinical features with a normal
      neurologic examination and normal neuroradiologic findings, AEDs should be
      avoided.

PMID- 15571519
TI  - Patients' perceptions of memory functioning before and after surgical
      intervention to treat medically refractory epilepsy.
AB  - PURPOSE: One risk associated with epilepsy surgery is memory loss, but perhaps
      more important is how patients perceive changes in their memories. This
      longitudinal study evaluated changes in memory self-reports and investigated how
      self-reports relate to changes on objective memory measures in temporal or
      extratemporal epilepsy patients who underwent surgery. METHODS: Objective memory
      (Wechsler Memory Scale-Revised) and subjective memory self-reports (Memory
      Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients
      approximately 6 months before and 6 months after surgery. A measure of depressive
      affect (Beck Depression Inventory-2nd Edition) was used to control variance
      attributable to emotional distress. RESULTS: Despite a lack of significant
      correlational relationships between objective and subjective memory for the
      entire sample, significant correlations between objective memory scores and self
      reports did emerge for a subset of patients who evidenced memory decline.
      Differences also were found in the subjective memory ratings of temporal lobe
      versus extratemporal patients. Temporal lobe patients rated their memories more
      negatively than did extratemporal patients and were more likely to report
      significant improvements in their memory after surgery. CONCLUSIONS: In general,
      patients were not accurate when rating their memories compared to other adults.
      However, patients with significant declines in their memories were sensitive to
      actual changes in their memories over time relative to their own personal
      baselines.

PMID- 15571520
TI  - The epidemiology of the comorbidity of epilepsy in the general population.
AB  - PURPOSE: To describe the epidemiology of somatic and psychiatric conditions in
      adults with epilepsy in the community and compare it to that of people without
      epilepsy. METHODS: A cross-sectional population-based study extracting data from
      the UK General Practice Research Database for the period 1995-1998. Age- and sex
      standardized prevalence rates were estimated for selected conditions and groups
      of conditions (categorized by ICD-9 chapters) in adults with epilepsy registered
      with primary care physicians. Results were compared with those in adults without
      epilepsy in the cohort, and prevalence ratios were calculated according to two
      broad age groups (16-64 and older than 64 years). RESULTS: Conditions common in
      the general population also were common in adults with epilepsy. Psychiatric
      disorders occurred twice as often, and the risk of somatic disorders was
      increased in people with epilepsy, with the exception of musculoskeletal and
      connective tissue disorders in older adults. The prevalence ratio of neoplasia,
      excluding intracranial tumors, was not increased in epilepsy. The prevalence
      ratio of brain tumors was particularly increased in young adults [prevalence
      ratio (PR), 70.7] and of meningiomas in older adults (PR, 91.9).
      Neurodegenerative conditions, particularly dementias and Alzheimer' disease (PR,
      6.3 and 8, respectively) and Parkinson' disease (PR, 3.2), appeared more
      frequently in people with epilepsy. Upper gastrointestinal bleed occurred more
      frequently in epilepsy (PR, 4.3), as did cardio- and cerebrovascular disorders,
      fractures, pneumonia and chronic lung diseases, and diabetes. Eczema,
      osteoarthritis, and rheumatoid arthritis did not occur more frequently in
      epilepsy. CONCLUSIONS: The prevalence ratio of many common psychiatric and
      somatic conditions is increased in adults with epilepsy who consult a primary
      care physician in the U.K. These findings may have implications in the diagnosis
      and management of epilepsy and coexisting conditions, as well as in health care
      provision.

PMID- 15571521
TI  - National and regional prevalence of self-reported epilepsy in Canada.
AB  - PURPOSE: To assess the point prevalence of self-described epilepsy in the general
      population nationally, provincially, and in different groups of interest.
      METHODS: We analyzed data from two national health surveys, the National
      Population Health Survey (NPHS, N=49,000) and the Community Health Survey (CHS,
      N=130,882). Both surveys captured sociodemographic information, as well as age,
      sex, education, ethnicity, household income, and labor force status of
      participants. Epilepsy was ascertained with only one question in both surveys.
      "Do you have epilepsy diagnosed by a health professional?" (NPHS) and "Do you
      have epilepsy?" (CHS). Prevalences were age-adjusted by using national standard
      populations at the time of each survey. Exact 95% confidence intervals were
      obtained. RESULTS: In the NPHS, 241 of 49,026 subjects described themselves as
      having been diagnosed with epilepsy, yielding a weighted point prevalence of 5.2
      per 1,000 [95% confidence interval (CI), 4.9-5.4]. In the CHS, 835 of 130,822
      subjects described themselves as having epilepsy, yielding a weighted point
      prevalence of 5.6 per 1,000 (95% CI, 5.1-6.0). Trends in differences in
      prevalence among some Canadian provinces were observed. Prevalence was
      statistically significantly higher in groups with the lowest educational level,
      lowest income, and in those unemployed in the previous year. Prevalence also was
      higher in nonimmigrants than in immigrants. CONCLUSIONS: The overall and group
      specific results are in keeping with those obtained in other developed countries
      by using different ascertainment methods. We discuss methodologic aspects related
      to the ascertainment of epilepsy in both surveys, and to the validity and
      implications of our findings.

PMID- 15571522
TI  - Epilepsy and driving in Japan.
AB  - PURPOSE: The driving regulations in Japan were amended in 2002, which lifted the
      absolute ban on driving by persons with epilepsy (PWE) and granted licenses to
      PWE after a 2-year seizure-free period. METHODS: To survey the effect of the new
      driving regulations, we sent questionnaires both to the driving authorities (DAs)
      and to doctors of the Japan Epilepsy Society (JES). RESULTS: Around 1,400 PWE
      legally obtained a driving license within 1 year after the amendment, licenses
      were rejected in 157, and 61 had the license withheld for <6 months. In most
      cases, the attending doctor assessed fitness for driving; 171 doctors responded
      to the questionnaire. One third of them commented on a positive change in
      attitude of PWE with respect to driving. Their main remarks included the need to
      shorten the seizure-free period to qualify for fitness to drive and the need for
      special guidelines for conditions such as rare seizure occurrence, recently
      diagnosed epilepsy, or reflex epilepsy. Problems of assessment identified
      included difficulty in deciding the time for reassessment, distress of PWE over
      cancellation of license, cost of the assessment, responsibility of the assessing
      doctors in case of seizure recurrence, and protection of privacy. They requested
      the DAs to promote publicity about the information and asked the JES to establish
      a guideline for assessing fitness to drive. CONCLUSIONS: The results highlighted
      the need for cooperation between the DAs and the JES for further amendment of the
      regulations as well as the importance of education for the public, patients, and
      professionals.

PMID- 15571523
TI  - Effects of add-on melatonin administration on antioxidant enzymes in children
      with epilepsy taking carbamazepine monotherapy: a randomized, double-blind,
      placebo-controlled trial.
AB  - PURPOSE: Melatonin has been shown to exhibit antioxidant, antiexcitotoxic, and
      free radical-scavenging properties in various animal models. The study was
      designed to assess its effects on the blood levels of antioxidant enzymes in
      children with epilepsy receiving carbamazepine (CBZ). METHODS: In a double-blind,
      randomized, parallel-group, placebo-controlled trial, we assessed the effect of
      add-on melatonin (6-9 mg/day for 14 days) on the antioxidant enzymes glutathione
      peroxidase (GPx) and glutathione reductase (GRd) in 31 children with epilepsy
      receiving CBZ monotherapy, who were seizure free at least for the last 6 months.
      The interaction of melatonin with CBZ and its active metabolite, carbamazepine
      10, 11-epoxide (CBZ-E), also was studied. RESULTS: An increase in GRd activity
      was noted in the melatonin group as compared with a decrease of the same enzyme
      in the placebo group. Changes in GPx activity failed to reach statistical
      significance. No significant changes were found in the serum levels of CBZ and
      CBZ-E in either group. CONCLUSIONS: The study suggests that melatonin exerts
      antioxidant activity in patients with epilepsy receiving CBZ therapy.

PMID- 15571524
TI  - High-grade atrioventricular block triggered by spontaneous and stimulation
      induced epileptic activity in the left temporal lobe.
AB  - Cardiac bradyarrhythmias may play a pivotal role in the pathophysiology of sudden
      unexpected death in epilepsy (SUDEP). We describe a patient with left temporal
      lobe epilepsy in whom high-grade atrioventricular conduction blocks were
      triggered by both spontaneous and stimulation-induced epileptic activity in the
      left temporal lobe. Electrophysiological data obtained by surface and
      intracranial electrodes point to a cerebral cardioarrhythmogenesis in the left
      amygdala and anterior hippocampus.

PMID- 15571525
TI  - Transient atrial fibrillation after the implantation of a vagus nerve stimulator.

PMID- 15571526
TI  - Efficacy and tolerability of the new antiepileptic drugs: commentary on the
      recently published practice parameters.

PMID- 15571529
TI  - Hyperventilation and epileptic seizures.

PMID- 15571530
TI  - Prospective association between low and high total and low-density lipoprotein
      cholesterol and coronary heart disease in elderly men.
AB  - OBJECTIVES: To examine the relationship between total cholesterol (TC) and low
      density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart
      disease (CHD) in elderly men. DESIGN: Prospective. SETTING: Population based.
      PARTICIPANTS: A sample of 2,424, Japanese-American men aged 71 to 93 was used.
      MEASUREMENTS: Six years of data on incident fatal plus nonfatal CHD were
      examined. RESULTS: Analysis revealed a significant U-shaped relationship between
      age-adjusted CHD rates and both TC and LDL-C. The ranges of TC and LDL-C with the
      lowest risk of CHD were 200 to 219 mg/dL and 120 to 139 mg/dL, respectively. As
      cholesterol concentrations declined and increased beyond these ranges, the risk
      of CHD increased. These U-shaped relationships remained significant after
      adjusting for age and other risk factors. CONCLUSION: The U-shaped associations
      between TC and LDL-C and CHD imply a complex relationship between lipids and CHD
      in late life. The results indicate that elevated lipid levels should continue to
      be treated in healthy elderly individuals, as they are in those who are younger,
      although pharmacologically lowering lipids to excessively low levels in the
      elderly may warrant further study, as does the contribution of subclinical
      frailty to the relationship of lipids to CHD risk.

PMID- 15571531
TI  - Primary cardiovascular events and serum lipid levels in elderly Japanese with
      hypercholesterolemia undergoing 6-year simvastatin treatment: a subanalysis of
      the Japan lipid intervention trial.
AB  - OBJECTIVES: To determine the relationship between serum lipid levels and the
      incidence of coronary events in older Japanese hypercholesterolemic patients
      without prior coronary heart disease (CHD). DESIGN: Post hoc subanalysis of the
      results in the Japan Lipid Intervention Trial. SETTING: A large-scale cohort
      observational study conducted throughout Japan. PARTICIPANTS: Men aged 35 to 70
      and postmenopausal women younger than 70 with serum total cholesterol (TC) level
      of 220 mg/dL or greater treated for 6 years with low-dose simvastatin (52,421
      total patients). After exclusion of 5,127 patients because of prior CHD and 4,934
      patients because of incomplete data, 42,360 patients were divided into an older
      (9,860 patients, aged 65-70, mean age 67.1) and younger (32,500 patients, younger
      than 65, mean age 54.9) group and analyzed. MEASUREMENTS: Fasting serum lipid
      levels were measured every 6 months. Major coronary events, including fatal or
      nonfatal myocardial infarction, and sudden cardiac death as the primary endpoint
      and other cardiovascular diseases, including onset of angina pectoris,
      cerebrovascular events, and any causes of death, as the secondary endpoints were
      monitored. RESULTS: Simvastatin treatment in older patients was as safe and
      effective as in younger patients. Incident rates of major coronary events were
      1.30 per 1,000 patient-years in the older group and 0.80 per 1,000 patient-years
      in the younger group. The incidence of a major coronary event was correlated to
      serum TC and low-density lipoprotein cholesterol (LDL-C) levels in both groups.
      The absolute risk of major coronary events in the older group was higher than in
      the younger group at any level of LDL-C, whereas the relative risk increased by
      1.7% with an elevation of each 1 mg/dL LDL-C level in both groups. In the older
      group, the risk of major coronary events also increased as triglyceride level
      increased, whereas the risk decreased as high-density lipoprotein cholesterol
      level increased above 60 md/dL. CONCLUSION: The LDL-C level-dependent increase of
      relative risk of CHD was similar in elderly and younger patients, whereas the
      absolute risk at any LDL-C level in elderly patients was higher than in younger
      patients.

PMID- 15571532
TI  - Ameliorating pain in nursing homes: a collaborative quality-improvement project.
AB  - OBJECTIVES: To evaluate a multifaceted intervention to improve pain-management
      processes of care and outcomes in nursing homes. DESIGN: Quasi-experimental,
      pretest/posttest. SETTING: Nursing homes in Rhode Island. PARTICIPANTS: Twenty
      one facilities. INTERVENTION: This project used a multifaceted collaborative
      intervention involving audit and feedback of pain management, education,
      training, coaching using rapid-cycle quality-improvement techniques, and inter
      nursing home collaboration. MEASUREMENTS: Pain-management processes of care and
      outcomes, measured using chart review and the Minimum Data Set. RESULTS: Of 21
      facilities, 17 completed the project. Postintervention, nursing homes increased
      the use of appropriate pain assessments (3.9% vs 43.8%, P<.001), pain intensity
      scales (15.6% vs 73.9%, P<.001), and nonpharmacological treatments (40.5% vs
      81.9%, P<.001). Prescriptions of World Health Organization Step II or Step III
      pain medications for residents with daily moderate or severe pain showed trends
      towards improvement (40.8% vs 50.6%, P=.057), but prescription of any pain
      medication (93.3% vs 94.6%, P=.710), change in pain medication (29.0% vs 30.1%,
      P=.386), and prescription of pain medications on a regularly scheduled basis
      (67.9% vs 69.5%, P=.370) did not. There was a 41.1% reduction in prevalence of
      pain (12.2% vs 7.2%, P=.032) between the pre- and postintervention time periods
      in the nursing homes that completed the project, whereas all the other facilities
      in Rhode Island (n=72) had only a 12.1% reduction (12.7% vs 11.2%, P=.286) during
      the same period. CONCLUSION: A multifaceted intervention improved pain-management
      process and outcome measures in nursing homes.

PMID- 15571533
TI  - Vision impairment and combined vision and hearing impairment predict cognitive
      and functional decline in older women.
AB  - OBJECTIVES: To determine the association between vision and hearing impairment
      and subsequent cognitive and functional decline in community-residing older
      women. DESIGN: Prospective cohort study. SETTING: Four metropolitan areas of the
      United States. PARTICIPANTS: A total of 6,112 women aged 69 and older
      participating in the Study of Osteoporotic Fractures (SOF) between 1992 and 1994.
      MEASUREMENTS: Five thousand three hundred forty-five participants had hearing
      measured, 1,668 had visual acuity measured, and 1,636 had both measured. Visual
      impairment was defined as corrected vision worse than 20/40. Hearing impairment
      was defined as the inability to hear a tone of 40 dB or greater at 2,000 hertz.
      Participants completed the modified Mini-Mental State Examination and/or a
      functional status assessment at baseline and follow-up. Cognitive and functional
      decline were defined as the amount of decline from baseline to follow-up that
      exceeded the observed average change in scores by at least 1 standard deviation.
      RESULTS: About one-sixth (15.7%) of the sample had cognitive decline; 10.1% had
      functional decline. In multivariate models adjusted for sociodemographic
      characteristics and chronic conditions, vision impairment at baseline was
      associated with cognitive (odds ratio (OR)=1.78, 95% confidence interval
      (CI)=1.21-2.61) and functional (OR=1.79, 95% CI=1.15-2.79) decline. Hearing
      impairment was not associated with cognitive or functional decline. Combined
      impairment was associated with the greatest odds for cognitive (OR=2.19, 95%
      CI=1.26-3.81) and functional (OR=1.87, 95% CI=1.01-3.47) decline. CONCLUSION:
      Sensory impairment is associated with cognitive and functional decline in older
      women. Studies are needed to determine whether treatment of vision and hearing
      impairment can decrease the risk for cognitive and functional decline.

PMID- 15571534
TI  - Comparison of routine glove use and contact-isolation precautions to prevent
      transmission of multidrug-resistant bacteria in a long-term care facility.
AB  - OBJECTIVES: To compare routine glove use by healthcare workers for all residents,
      without use of contact-isolation precautions, with contact-isolation precautions
      for the care of residents who had vancomycin-resistant enterococci or methicillin
      resistant Staphylococcus aureus isolated from a clinical culture. DESIGN: Random
      allocation of two similar sections of the skilled-care unit to one of the
      infection-control strategies during an 18-month study period. SETTING: Skilled
      care unit of a 667-bed acute- and long-term care facility. PARTICIPANTS: All
      residents present or admitted to the skilled-care unit from June 1, 1998, through
      December 7, 1999. MEASUREMENTS: Resident acquisition of four antimicrobial
      resistant organisms (methicillin-resistant Staphylococcus aureus, vancomycin
      resistant enterococci, or extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae or Escherichia coli). All isolates were strain typed. The facility
      level costs associated with each strategy were estimated. RESULTS: Resident
      acquisition of antimicrobial-resistant organisms was no different in the glove
      use and isolation-precautions sections (31 episodes (1.5 per 1,000 resident-days)
      vs 38 episodes (1.6 per 1,000 resident-days)). Acquisition of either of two
      prevalent K. pneumoniae strains was more likely (P=.06) in residents in the
      isolation-precautions section. The estimated costs of contact-isolation
      precautions were 40% greater than those of routine glove use. CONCLUSION: There
      was a similar frequency of transmission of antimicrobial-resistant bacteria in
      the two study sections; there was evidence for resident-to-resident K. pneumoniae
      transmission in the isolation-precautions section. Routine glove use for
      healthcare workers, which decreases resident social isolation and healthcare
      facility costs, may be preferable in many long-term care facilities.

PMID- 15571535
TI  - Indicators of recurrent hospitalization for pneumonia in the elderly.
AB  - OBJECTIVES: To identify modifiable risk factors of late unplanned readmissions
      for elderly with community-acquired pneumonia. DESIGN: A case-control study.
      SETTING: Three university-affiliated tertiary-care hospitals. PARTICIPANTS: Two
      hundred four case-control pairs. Case patients referred to all patients
      readmitted with pneumonia 30 days to 1 year after discharge. Control subjects
      were matched for age, admission date, and residence before admission.
      MEASUREMENTS: Baseline sociodemographic information, clinical data, activity of
      daily living (ADLs) information, and Charlson Comorbidity Index score were
      obtained. The Pneumonia Severity Index was calculated with swallowing dysfunction
      and pattern and extent of radiographic abnormalities, antimicrobial coverage, and
      total duration recorded. RESULTS: Median time to readmission was 123 days
      (interquartile range=65-238 days). Readmission was not associated with increased
      severity or length of hospital stay. In a Cox proportional hazards regression
      model, swallowing dysfunction (hazard ratio (HR)=2.15, 95% confidence interval
      (CI)=1.46-2.97), current smoking (HR=2.04, 95% CI=1.48-2.82), use of
      tranquilizers (HR=1.5, 95% CI=1.02-2.22), and lower ADL scores (HR=1.06, 95%
      CI=1.02-1.10) were independently associated with readmission for pneumonia. The
      receipt of angiotensin-converting enzyme inhibitors (HR=0.46, 95% CI=0.27-0.78)
      and prior pneumococcal vaccination (HR=0.59, 95% CI=0.42-0.82) had a protective
      effect. CONCLUSION: Although there are limited effective measures to improve
      functional status, preventive strategies that include smoking cessation and
      pneumococcal vaccination should be actively pursued. Routine evaluation of
      swallowing dysfunction and use of pharmacological agents to improve the cough
      reflex deserve further evaluation in multicenter controlled trials.

PMID- 15571536
TI  - Resistance training in the early postoperative phase reduces hospitalization and
      leads to muscle hypertrophy in elderly hip surgery patients--a controlled,
      randomized study.
AB  - OBJECTIVES: To better understand how immobilization and surgery affect muscle
      size and function in the elderly and to identify effective training regimes.
      DESIGN: A prospective randomized, controlled study. SETTING: Bispebjerg
      University Hospital, Copenhagen, Denmark. PARTICIPANTS: Thirty-six patients (aged
      60-86) scheduled for unilateral hip replacement due to primary hip
      osteoarthrosis. INTERVENTION: Patients were randomized to standard home-based
      rehabilitation (1 h/d x 12 weeks), unilateral neuromuscular electrical
      stimulation of the operated side (1 h/d x 12 weeks), or unilateral resistance
      training of the operated side (3/wk x 12 weeks). MEASUREMENTS: Hospital length of
      stay (LOS), quadriceps muscle cross-sectional area (CSA), isokinetic muscle
      strength, and functional performance. Patients were tested presurgery and 5 and
      12 weeks postsurgery. RESULTS: Mean+/-standard error LOS was shorter for the
      resistance training group (10.0+/-2.4 days, P<.05) than for the standard
      rehabilitation group (16.0+/-7.2 days). Resistance training, but not electrical
      stimulation or standard rehabilitation, resulted in increased CSA (12%, P<.05)
      and muscle strength (22-28%, P<.05). Functional muscle performance increased
      after resistance training (30%, P<.001) and electrical stimulation (15%, P<.05)
      but not after standard rehabilitation. CONCLUSION: Postoperative resistance
      training effectively increased maximal muscle strength, muscle mass, and muscle
      function more than a standard rehabilitation regime. Furthermore, it markedly
      reduced LOS in elderly postoperative patients.

PMID- 15571537
TI  - Epidemiology and short-term outcomes of injured medicare patients.
AB  - OBJECTIVES: To describe characteristics and short-term outcomes of Medicare
      patients hospitalized after injuries in 1999. DESIGN: Analysis of national
      population-based case series. SETTING: Hospitalized Medicare patients.
      PARTICIPANTS: All fee-for-service Medicare patients aged 65 and older admitted
      for the first time in 1999 with principal injury diagnoses (International
      Classification of Diseases, Ninth Revision, codes 800-904, 910-929, 940-957,
      959). MEASUREMENTS: Incidence rates, stratified by anatomic location (hip, other
      extremity, spine, head, chest, other), sex, and age group (65-74, 75-84, >or=85).
      For each category, Charlson comorbidity scores, Abbreviated Injury Scores,
      hospital length of stay, discharge disposition, hospital mortality, 30-day
      mortality, and readmissions within 30 days of discharge. RESULTS: A total of
      439,605 persons were admitted at least once (crude rate 1,654/100,000). Rates of
      hospitalization increased with age and were generally higher in women (except
      head injuries). Comorbidities were more common in men. Hip fractures constituted
      46.6% of cases and other extremity injuries another 30.7%. Hospital mortality
      (3.7% overall) increased with age, was greater in men, and was highest in
      patients with head injuries. The proportion discharged to skilled nursing
      facilities (43.8% overall, range 10.0-61.9% by age/sex/anatomic category) also
      increased with age, was higher in women, and was highest in patients with hip
      fractures. Slightly more than one-tenth (12.3%) of patients were readmitted
      within 30 days. Thirty-day mortality was 2.0 times hospital mortality (range 1.2
      3.4 by category). CONCLUSION: Most injuries resulting in hospitalization for the
      Medicare population involve the extremities, but other injuries have higher
      mortality. Many injured patients are not discharged home but receive additional
      institutional care. Thirty-day survival is much lower than observed hospital
      survival. Further studies of injuries using Medicare data are warranted.

PMID- 15571538
TI  - Disruptive behaviors in Veterans Affairs nursing home residents: how different
      are residents with serious mental illness?
AB  - OBJECTIVES: To determine the prevalence and correlates of behavior problems of
      residents of Veterans Affairs (VA) nursing homes and to compare residents with
      serious mental illness (SMI) with other resident groups. DESIGN: This study
      combined cross-sectional resident assessments with administrative data for all
      residents in VA nursing homes. Multivariate ordinal logistic regression was used
      to evaluate associations between resident characteristics and problem behaviors.
      SETTING: Nursing home care units in the VA healthcare system. PARTICIPANTS: A
      total of 9,618 nursing home residents assessed as part of the VA's April 2001
      national resident census. MEASUREMENTS: The Patient Assessment Instrument
      assessed each resident's verbally disruptive, physically aggressive, and socially
      inappropriate behaviors in the prior 4 weeks. Functional limitations in eating,
      mobility, toileting, and transfer were assessed. Diagnoses were evaluated for the
      stay and up to 6 months before assessment. RESULTS: Almost one-fifth (17.9%) of
      residents received a diagnosis of SMI. Residents with SMI or dementia had greater
      behavior problems than residents with neither condition. Residents with SMI (and
      without dementia) exhibited more verbal disruption than residents with dementia
      (and without SMI), but the two subgroups did not differ in physically aggressive
      or socially inappropriate behavior. CONCLUSION: Many VA nursing home residents
      have SMI. Their level of behavior problems is comparable with that of residents
      with dementia. Clinical practice and nursing home staff training must encompass
      geriatric mental health and behavior management to meet the needs of residents
      with SMI.

PMID- 15571539
TI  - Patterns of utilization for the Minnesota senior health options program.
AB  - OBJECTIVES: To compare the use of medical services provided under the Minnesota
      Senior Health Options (MSHO) (a special program designed to serve dually eligible
      older persons) with that provided to controls who received fee-for-service
      Medicare and Medicaid managed care. DESIGN: Quasi-experimental design using two
      control groups; separate matched cohort and rolling cross-sectional analyses;
      regression models used to adjust for case-mix differences. SETTING: Urban
      Minnesota community and nursing home long-term care. PARTICIPANTS: Dually
      eligible elderly MSHO enrollees in the community and in nursing homes were
      compared with two sets of controls; one was drawn from nonenrollees living in the
      same area (control-in) and another from comparable persons living in another
      urban area where the program was not available (control-out). Cohorts living in
      the community and in nursing homes were included. MEASUREMENTS: Use of hospitals
      and emergency rooms, physician visits. RESULTS: In the community cohort, there
      were no significant differences in hospital admission rates or in hospital days.
      MSHO enrollees had significantly fewer preventable hospital admissions and
      significantly fewer preventable emergency services than the control-in group.
      MSHO nursing home enrollees had significantly fewer hospital admissions than
      either control group with or without adjustment at 12 and 18 months. MSHO
      enrollees had significantly fewer hospital days and preventable hospitalizations
      than the control-in group. MSHO enrollees had significantly fewer emergency room
      visits and preventable emergency room visits than either control group.
      CONCLUSION: In general, the results of this evaluation are mixed but favor MSHO.
      The effect of MSHO was stronger for nursing home enrollees than community
      enrollees. The lower rate of preventable hospitalizations and emergency room
      visits of MSHO enrollees suggests that MSHO affected the process of care by
      providing more of some types of preventive and community-care services for
      community residents.

PMID- 15571540
TI  - Subjective memory deterioration and future dementia in people aged 65 and older.
AB  - OBJECTIVES: To study whether subjective memory deterioration is associated with
      future dementia in older people. DESIGN: A population-based prospective cohort
      study begun in 1994 with biennial follow-up interviews. SETTING: Community-based
      members of Group Health Cooperative, a large health maintenance organization in
      the Seattle area. PARTICIPANTS: A sample of 1,883 subjects, dementia free, aged
      65 and older, who scored 91 or higher on the 100-point Cognitive Ability
      Screening Instrument (CASI) at study entry. MEASUREMENTS: Subjective memory was
      assessed by asking whether memory had changed on 5-point Likert scales (e.g.,
      1=definitely improved, 3=no change, 5=definitely deteriorated) with regard to
      five items: remembering names, faces, friends, and appointments and judging the
      time. The items were summed for a possible total score ranging from 5 to 25.
      Subjective memory deterioration was defined as present if the total score was 20
      or above. Cognitive performance was measured using the CASI. Incident dementia
      cases were identified using Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria. RESULTS: Of 1,883 subjects, 126 developed
      dementia during 5 years of follow-up. Subjective memory deterioration was
      associated with cognitive decline and incident dementia. Age modified the
      association between subjective memory deterioration and future dementia. For
      persons reporting subjective memory deterioration at the ages of 70, 75, and 80,
      the hazard ratios of developing dementia were 6.0 (95% confidence interval
      (CI)=2.1-18), 3.2 (95% CI=1.6-6.2) and 1.6 (95% CI=0.86-3.1), respectively.
      CONCLUSION: Subjective memory deterioration was found to precede the development
      of dementia in older people with normal cognitive screening results. These
      findings suggest that a high level of subjective memory deterioration in persons
      with normal objective cognitive function may identify a subset of individuals at
      greater risk for developing dementia.

PMID- 15571541
TI  - What symptoms of depression predict mortality in community-dwelling elders?
AB  - OBJECTIVES: To determine which symptoms of depression are most likely to increase
      the risk of mortality in a biracial sample of older adults. DESIGN: Cross
      sectional and longitudinal study. SETTING: Baseline and mortality follow-up in
      urban and rural North Carolina. PARTICIPANTS: Four thousand one hundred sixty-two
      African-American and white elders aged 65 to 105 at baseline (mean age 73).
      MEASUREMENTS: Sociodemographic and health factors and four subscales of the
      Center for Epidemiologic Studies Depression Scale (negative affect, positive
      affect, somatic symptoms, and interpersonal function) were determined at baseline
      (1986-87). Mortality was assessed over 10 years of follow-up (through 1996).
      RESULTS: Fifty-one percent of the sample died over the 10-year follow-up. In
      controlled Cox proportional hazards modeling, those who scored lower on the
      positive affect scale were significantly more likely to die over the 10-year
      follow-up (hazard ratio=1.12, 95% confidence interval=1.05-1.18). For those who
      scored higher on the negative affect scale, the somatic scale, and the
      interpersonal scale, there was no increased risk for mortality in controlled
      analyses. CONCLUSION: These findings suggest that subjective views of well-being
      may be more important predictors of mortality in older adults than the classic
      symptoms of depression, such as negative affect and somatic symptoms.

PMID- 15571542
TI  - Using the minimum data set to select nursing home residents for interview about
      pain.
AB  - OBJECTIVES: To determine how many nursing home residents can provide stable
      responses to a simple pain interview and whether a Minimum Data Set (MDS)
      cognitive performance measure can be used to identify these residents. DESIGN:
      Cross-sectional descriptive study. SETTING: Thirty-three community-based nursing
      homes. PARTICIPANTS: Eight hundred ninety-five nursing home residents.
      MEASUREMENTS: Resident completion rate, stability, and interrater reliability of
      a four-item interview derived from the Geriatric Pain Measure were calculated.
      Demographic data and MDS items concerning pain and memory were obtained from
      medical records. RESULTS: Overall, 835 residents were able to answer all four
      interview questions. At the lowest MDS recall score of 0, 52.7% of residents were
      able to complete all questions. All residents able to respond to the interview
      achieved high stability (kappa=0.633, P<.001). Overall, 62.8% of residents with
      daily pain or activity-limiting pain on interview did not have daily or moderate
      to severe pain recorded on the MDS. Residents who had lower MDS recall scores
      were significantly less likely (P=.004) to be appropriately identified on the
      MDS. CONCLUSION: Residents with a low MDS recall score were significantly less
      likely to be noted on the MDS as having serious pain despite being able to
      complete a simple yes/no interview about pain in a stable fashion. Nursing staff
      should attempt to ask all residents direct questions about pain. Surveyors may
      restrict direct questioning to those residents with an MDS recall score of 1 or
      higher if time is an important consideration. Adjustment for MDS-derived
      prevalence of pain based on residents' cognitive status is questionable.

PMID- 15571543
TI  - Persistent pain in frail older adults after hip fracture repair.
AB  - OBJECTIVES: To identify factors associated with persistent hip pain in elderly
      hip fracture patients with physical frailty. DESIGN: Cohort study. SETTING:
      Community-based study conducted at academic medical center. PARTICIPANTS: Eighty
      eight men and women (mean age+/-standard deviation 80+/-7 years) with a recent
      hip fracture (mean 14.5+/-4.8 weeks after hip fracture repair) and physical
      frailty, defined as a modified Physical Performance Test Score between 12 and 28,
      enrolled in an exercise intervention trial. MEASUREMENTS: Dependent variable was
      self-report of moderate to severe regional hip pain in the week preceding the
      baseline interview. Independent variables were self-reported demographic
      information, health characteristics, and activity of daily living (ADL) function;
      Yesavage Mood Score (YMS); 36-item Short Form percentile scores; and objective
      measurements of lower extremity strength, range of motion, balance, and gait.
      RESULTS: Forty-two percent of the sample reported moderate or severe hip pain at
      the baseline assessment. Moderate/severe pain was related to difficulty with ADL
      performance and multiple measures of quality of life. Variables independently
      associated with moderate/severe hip pain were frequency of pain medication use
      (adjusted odds ratio (AOR)=5.75, 95% confidence interval (CI)=2.23-14.82,
      P=.003), YMS score (AOR=2.69, 95% CI=1.18-6.12, P=.02), and knee extension at 60
      degrees /s in the fractured limb (AOR=0.96, 95% CI=0.92-1.0, P=.05, model
      coefficient of determination=0.34). CONCLUSION: Persistent hip pain is a frequent
      symptom in frail elderly community-dwelling hip fracture patients. Pain
      medication use, symptoms of depression, and skeletal muscle weakness of the
      fractured leg are independent correlates of moderate to severe hip pain in this
      patient population. Clinicians should assess for, and address, persistent pain in
      this patient population.

PMID- 15571544
TI  - Emergence and transmission of amantadine-resistant influenza A in a nursing home.
AB  - OBJECTIVES: To prospectively detect amantadine-resistant influenza when
      amantadine was used for influenza A outbreak control. DESIGN: Prospective
      clinical surveillance and viral culture of all new respiratory illnesses during
      the course of amantadine prophylaxis. SETTING: A 721-bed, 14-ward nursing home
      for veterans and spouses during an influenza A outbreak (1993-94). PARTICIPANTS:
      Residents of a veterans hospital and their spouses. MEASUREMENTS: Nasopharyngeal
      and throat viral culture. All residents with positive cultures who developed new
      respiratory symptoms while receiving or residing on a unit receiving amantadine
      prophylaxis had antiviral-resistance testing and polymerase chain reaction
      restriction analyses performed. RESULTS: Amantadine prophylaxis was administered
      sequentially on nine of 14 wards to all well residents for 14 to 31 days/ward to
      control influenza outbreaks between December 9, 1993, and January 28, 1994.
      Amantadine treatment was simultaneously provided to 29 ill residents. Between
      December 3, 1993, and January 22, 1994, 68 culture-positive cases of influenza A
      were detected. Twenty subjects were receiving or residing on units receiving
      amantadine prophylaxis. Amantadine sensitivity testing could be performed on 16
      residents; 12 residents had amantadine resistant strains. Four of the 12 had not
      received any antiviral treatment. Illness onset ranged from 1 to 22 days after
      amantadine prophylaxis was begun on the individual's unit. Two ribonucleic acid
      (RNA) mutations in the gene coding the M2 protein transmembrane region were
      observed that were clustered in time and space. Isolates from two roommates, one
      receiving amantadine for 18 days and one on no antiviral, had identical RNA
      sequences. CONCLUSION: Antiviral resistance may be responsible for failure of
      prophylaxis in nursing home outbreaks. Strategies that use different classes of
      antivirals for prophylaxis and treatment may limit emergence and transmission of
      resistant virus.

PMID- 15571545
TI  - Lower all-cause, cardiovascular, and cancer mortality in centenarians' offspring.
AB  - OBJECTIVES: To assess the cause of death for centenarians' offspring and
      controls. DESIGN: Cross-sectional study. SETTING: Community-based, nationwide
      sample. PARTICIPANTS: Family pedigree information was collected on 295 offspring
      of centenarians (from 106 families with a parent already enrolled in the
      nationwide New England Centenarian Study) and on 276 controls (from 82 control
      families) from 1997 to 2000. Controls were individuals whose parents were born in
      the same year as the centenarians but at least one of whom died at the average
      life expectancy. MEASUREMENTS: Age at death and cause of death. RESULTS:
      Centenarians' offspring had a 62% lower risk of all-cause mortality (P<.001), a
      71% lower risk of cancer-specific mortality (P=.002), and an 85% lower risk of
      coronary heart disease-specific mortality (P<.001). Significant differences were
      not found for other causes of death. However of those who died centenarian
      offsprings dead at a significantly younger age than controls. CONCLUSION: These
      findings suggest that centenarians' offspring have lower all-cause mortality
      rates and cause-specific mortality rates for cancer and coronary heart disease.
      These results suggest that mechanisms for survival to exceptional old age may go
      beyond the avoidance or delay of cardiovascular disease and also include the
      avoidance or delay of cancer. Moreover survival advantage of centenarian
      offsprings may not be due to factors related to childhood mortality. Ultimately,
      survival to exceptional old age may involve lower susceptibility to a broad range
      of age-related diseases, perhaps secondary to inhibition of basic mechanisms of
      aging.

PMID- 15571546
TI  - Low testosterone is associated with decreased function and increased mortality
      risk: a preliminary study of men in a geriatric rehabilitation unit.
AB  - OBJECTIVES: To evaluate whether low testosterone levels are associated with
      greater depression or poorer function in a geriatric rehabilitation unit. DESIGN:
      Retrospective review. SETTING: Geriatric rehabilitation unit. MEASUREMENTS: Low
      testosterone levels were defined as total testosterone of 3.0 ng/mL or less or
      free testosterone of 9.0 pg/mL or less. Age, ethnicity, weight, depression,
      ambulation, length of rehabilitation, and 6-month rehospitalization and mortality
      rates were obtained. Overall illness severity was determined using the Cumulative
      Illness Rating Scale for Geriatrics. RESULTS: Low testosterone levels were
      present in 29 of 44 (65.9%) men. There were no significant differences between
      men with low and normal testosterone levels in ethnicity, age, weight,
      depression, and overall illness severity. Lower testosterone levels were
      correlated with decreased ability to ambulate and transfer (Spearman P>.34;
      P<.05). There were no significant differences between men with low and normal
      testosterone in length of stay on the rehabilitation unit (mean+/-standard
      deviation= 19.6+/-11.6 vs 17.7+/-17.5 days, P=.68) or rehospitalization rates
      (41.4% vs 26.7%; P=.34). Men with low testosterone had a trend toward increased 6
      month mortality (31.0% vs 6.7%; chi(2)=3.3, P=.07) and shorter survival time (log
      rank=3.2; df 1, P=.07). After entering testosterone and variables with potential
      prognostic significance for mortality in a stepwise manner in a Cox regression
      analysis, there was a significant mortality risk associated with low testosterone
      (hazard ratio=27.9, 95% confidence interval=2.0-384.0; P=.01). CONCLUSION: Low
      testosterone levels were correlated with decreased physical function and
      increased risk for 6-month mortality. Prospective studies with larger sample
      sizes and better standardized testosterone measures are needed to confirm these
      findings.

PMID- 15571547
TI  - The concurrent use of anticholinergics and cholinesterase inhibitors: rare event
      or common practice?
AB  - OBJECTIVES: To measure the prevalence of anticholinergic use cross-sectionally in
      patients receiving cholinesterase inhibitors and to describe change in use of
      anticholinergics upon inception of cholinesterase inhibitor treatment. DESIGN:
      Cross-sectional and inception cohort studies. SETTING: State of Iowa.
      PARTICIPANTS: Iowa Medicaid beneficiaries aged 50 and older with a pharmacy claim
      for a cholinesterase inhibitor during January 1997 through February 2000.
      MEASUREMENTS: Anticholinergic use was determined for all patients with a
      cholinesterase inhibitor pharmacy claim during January and February of 2000. A
      frequency distribution of all anticholinergics was compiled, with emphasis placed
      on those considered inappropriate in the elderly. In a separate analysis,
      anticholinergic use was determined at two points: 90 days before and after
      cholinesterase inhibitor inception. RESULTS: Of 557 patients receiving a
      cholinesterase inhibitor, 197 (35.4%) received an anticholinergic concurrently.
      Of all anticholinergics, 74.5% (178/239) had been identified as inappropriate for
      use in the elderly, 22.2% (53/239) under any circumstances. At the time of
      cholinesterase inhibitor inception, 30.2% (143/474) and 33.5% (159/474) of
      patients received an anticholinergic 90 days before and 90 days after inception,
      respectively. Increases in anticholinergic prescribing upon cholinesterase
      inhibitor inception exceeded decreases (Wilcoxon signed-rank test, S=529,
      P=.020). CONCLUSION: The concurrent use of anticholinergics and cholinesterase
      inhibitors is common although rarely appropriate. Patients with Alzheimer's
      disease deserve to receive the optimum benefit from cholinesterase inhibitor
      treatment, which can only be achieved through diligent and appropriate use of
      concurrent pharmacotherapy.

PMID- 15571548
TI  - Footlift asymmetry during obstacle avoidance in high-risk elderly.
AB  - OBJECTIVES: To test the hypothesis that vertical footlift asymmetries and low
      obstacle clearing distance during obstacle avoidance are characteristics of
      elderly people classified as high risk for falls. DESIGN: Controlled cross
      sectional design with two conditions to cue selection of the foot-for-step
      initiation: sound cue and visual cue. SETTING: Senior independent living
      facilities. PARTICIPANTS: Eighteen community-dwelling elderly with a history of
      falling or prolonged Timed Up and Go score greater than 13.5 seconds, 16 elderly
      with no fall history and Timed Up & Go score of 13.5 seconds or less, and 15
      younger subjects. MEASUREMENTS: Video kinematic analysis of bilateral footlift
      displacement and velocity using reflective markers as subjects stepped over foam
      obstacles scaled to a maximum tolerated height. RESULTS: High-risk elders
      contacted the obstacle more frequently and had significantly greater vertical
      footlift asymmetries adjusted for obstacle/subject height (mean+/-standard error
      asymmetry index for sound cue 3.25+/-0.42 cm, for visual cue 2.51+/-0.45 cm) than
      low-risk and younger subjects (P<.001). In low-risk elderly and younger subjects,
      the asymmetry index approached 0, which indicated symmetrical lower limb
      movements when stepping over the obstacles. CONCLUSION: High-risk elderly show a
      marked asymmetry in foot clearance while stepping over an obstacle, with the lag
      foot clearing the obstacle at a much lower distance than the lead foot. Possible
      mechanisms responsible for these findings (limited hip extension and deficits in
      executive cognitive function) are discussed.

PMID- 15571549
TI  - Incidence of loss of ability to walk 400 meters in a functionally limited older
      population.
AB  - OBJECTIVES: To assess the incidence of and factors related to nondisabled but
      functionally limited older adults aged 75 to 85 years losing the ability to walk
      400 m. DESIGN: Observational study with average follow-up of 21 months. SETTING:
      Community. PARTICIPANTS: At baseline, 101 persons with objective signs of
      functional limitations and intact cognitive function agreed to participate in the
      study. Of these, 81 were able to walk 400 m at baseline, and 62 participated in
      the follow-up examination. MEASUREMENTS: Mobility disability was defined as an
      inability to complete a 400-m walk test. At baseline, eligible participants
      (n=81) had the ability to walk 400 m, scored between 4 and 9 on the Short
      Physical Performance Battery (SPPB; range 0-12), and scored 18 or more on the
      Mini-Mental State Examination. Demographics, difficulty in daily activities,
      disease status, behavioral risk factors, and muscle strength were assessed at
      baseline and follow-up. RESULTS: Of 62 persons at follow-up, 21 (33.9%) developed
      incident mobility disability. The strongest predictors of loss of mobility were
      the time to complete the 400-m walk at baseline (odds ratio (OR)=1.6 per 1-minute
      difference, 95% confidence interval (CI)=1.04-2.45), and decline in SPPB score
      over the follow-up (OR=1.4 per 1-point difference, 95% CI=1.01-1.92). CONCLUSION:
      Older persons with functional limitations have a high rate of loss of ability to
      walk 400 m. The 400-m walk test is a highly relevant, discrete outcome that is an
      ideal target for testing preventive interventions in vulnerable older
      populations.

PMID- 15571550
TI  - Use of self-report to predict ability to walk 400 meters in mobility-limited
      older adults.
AB  - OBJECTIVES: To determine whether the ability to walk 400 m could be predicted
      from self-reported walking habits and abilities in older adults and to develop an
      accurate self-report measure appropriate for observational trials of mobility
      when functional measures are impractical to collect. DESIGN: Cross-sectional.
      SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred
      fifty community-dwelling older men and women (mean age+/-standard error= 79.8+/
      0.3). MEASUREMENTS: An 18-item questionnaire assessing walking habits and ability
      was administered to each participant, followed by a 400-m walk test. Ninety-eight
      (65%) volunteers were able to complete the 400-m walk; 52 (35%) were unable.
      Logistic regression was performed using response items from a questionnaire as
      predictors and 400-m walk as the outcome. RESULTS: Three questions (Do you think
      you could walk one-quarter of a mile now without sitting down to rest. Because of
      a health or physical problem, do you have difficulty walking 1 mile? Could you
      walk up and down every aisle of a grocery store without sitting down to rest or
      leaning on a cart?) were predictive of 400-m walking ability and were included in
      the model. If participants answered all three questions compatible with the
      inability to walk 400 m, there was a 91% probability that they were unable to
      walk 400 m, with a sensitivity of 46% and a specificity of 97%. CONCLUSION: A
      three-item self-report developed in the study was able to accurately predict
      mobility disability. The utility of this instrument may be in evaluating self
      reported mobility in large observational trials on mobility when functional
      mobility tasks are impractical to collect.

PMID- 15571551
TI  - Self-reported delay in seeking care has poor validity for predicting adverse
      outcomes.
AB  - OBJECTIVES: To determine whether self-reports of delayed care predict increased
      mortality and functional decline in community-dwelling elderly. DESIGN:
      Longitudinal cohort study. SETTING: Five counties in North Carolina.
      PARTICIPANTS: A total of 4,162 randomly sampled individuals aged 65 and older.
      MEASUREMENTS: The primary outcome was the proportional hazard ratio (HR) for
      death in cohorts stratified by self-reports of delayed or foregone care. A
      secondary outcome, functional decline, measured the cohorts' odds of developing
      increased dependency in activities of daily living (ADLs). Control variables
      included predisposing, enabling, and need factors. RESULTS: Of 3,964 eligible
      participants reporting, 61% never, 27% once in a while, and 12% quite often
      delayed care. Over 3 years, 13% of participants died, and 17% developed increased
      ADL dependency. Nevertheless, in unadjusted and adjusted models, neither 3-year
      mortality HRs nor the odds of functional decline differed between cohorts
      reporting varying degrees of delayed care. Survival probabilities remained higher
      for 15 years among those reporting delaying care often. CONCLUSION: The inability
      of self-reported delay to predict adverse outcomes in community-dwelling elderly
      suggests the need for better understanding and support of the care-seeking
      process and additional measures of timeliness of access.

PMID- 15571552
TI  - Genetic testing has no place as a routine diagnostic test in sporadic and
      familial cases of Alzheimer's disease.
AB  - The challenges inherent in diagnosing and treating patients with Alzheimer's
      disease are increasing. Early diagnosis and modification of risk factors have
      received growing attention from the media in recent years. As a result, the
      general public, and patients and family members, are increasingly better informed
      about the disease, its genetic background, and the possibilities for treatment.
      The physician is often faced with questions about hereditary patterns within the
      family and with requests to perform genetic testing. Children, with increasing
      frequency, ask for a separate appointment with the treating physician, during the
      patient's life or after the patient has died, to discuss whether they are likely
      to get the disease and whether genetic tests should be performed. In this paper,
      some of the clinical and ethical questions that physicians face are explored.
      Arguments as to why we think routine genetic assessment should not be part of the
      diagnostic examination of the patient suspected of Alzheimer's disease are given.

PMID- 15571553
TI  - Who wants to enter a long-term care facility in a rapidly aging non-Western
      society? Attitudes of older Koreans toward long-term care facilities.
AB  - To estimate future demand for institutional long-term care (LTC) by Koreans, the
      intention to use LTC facilities was estimated, and the underlying influencing
      factors were explored. Data from the Korean National Survey of LTC Need in the
      Elderly compiled in 2001 were used, and 1,850 people aged 65 and older who were
      classified as the targets for LTC in the survey and for whom complete data were
      available were sampled. The following influencing variables were selected based
      on Anderson's service-use model: demographics, social structural factors, family
      and community resources, and felt and assessed needs. The result shows that, of
      all the participants, 18.8% intended to use LTC facilities. A stronger intention
      was related to younger age, Christian religion, fewer children, lower family
      income, higher chronic comorbidity, and more education. The rapid
      industrialization of Korea has lead to a transition from the traditional family
      centered mode of caregiving to a nontraditional one, but the intention to use LTC
      facilities is still lower than in Western developed countries. Regarding family
      resources, the effect of extended families comprising three or more generations
      is not as significant as expected, but children continue to be regarded as the
      main resources for LTC. The recent introduction of nontraditional religions to
      Korea has had a positive effect on intention to use LTC facilities, suggesting
      that cultural factors influence their use.

PMID- 15571554
TI  - Black and white differences in cognitive function test scores: what explains the
      difference?
AB  - Several studies have reported that older black and Latino adults have lower
      cognitive function test scores than older white adults, but few have
      comprehensively examined reasons for score differences. This study evaluates
      whether differences in health and socioeconomic indicators, including literacy
      level, can explain differences in cognitive function test scores between older
      black and white adults.

PMID- 15571555
TI  - Developing a comprehensive interdisciplinary senior healthcare practice.
AB  - The PeaceHealth Senior Health and Wellness Center (SHWC) provides primary care
      coordinated by geriatricians and an interdisciplinary office practice team that
      addresses the multiple needs of geriatric patients. The SHWC is a hospital
      outpatient clinic operated as a component of an integrated health system and is
      focused on the care of frail elders with multiple interacting chronic conditions
      and management of chronic disease in the healthier older population. Based on the
      Chronic Care Model, the SHWC strives to enhance coordination and continuity along
      the continuum of care, including outpatient, inpatient, skilled nursing, long
      term care, and home care services. During its development, a patient-centered
      approach was used to identify senior service needs. The model emphasizes team
      development, integration of evidence-based geriatric care, site-based care
      coordination, longer appointment times, "high touch" service qualities,
      utilization of an electronic medical record across care settings, and a
      prevention/wellness orientation. This collection of services addresses the
      interrelationships of all senior issues, including nutrition, social support,
      spiritual support, caregiver support, physical activity, medications, and chronic
      disease. The SHWC provides access in an environment sensitive to the special
      needs of seniors, with a staff trained to meet those needs. The SHWC business
      model attempts to improve access and quality of care to seniors in a mostly
      noncapitated healthcare setting, while also attempting to remain financially
      viable.

PMID- 15571558
TI  - Quality improvement in nursing homes: the elephants in the room.

PMID- 15571559
TI  - Home hospital-toward a tighter definition.

PMID- 15571560
TI  - Prescription error resulting in valproic acid intoxication.

PMID- 15571561
TI  - Effect of temperature on swallowing reflex in elderly patients with aspiration
      pneumonia.

PMID- 15571562
TI  - Adult Still's disease in a 75-year-old patient.

PMID- 15571563
TI  - Septic shock in an elderly patient on dialysis: enema-induced rectal injury
      confusing the clinical picture.

PMID- 15571564
TI  - Relation between retirement and subsequent health status in highly educated older
      men.

PMID- 15571565
TI  - Cognitive screening raises fears of identity theft.

PMID- 15571566
TI  - Practice differences between the United States and Canada.

PMID- 15571567
TI  - Psychometric properties of the satisfaction with the nursing home instrument
      (Chinese version).

PMID- 15571569
TI  - Should patients with GERD be screened once at least for Barrett's epithelium?
      Pro: The need to screen GERD patients for Barrett's esophagus--a greater yield
      than surveillance.

PMID- 15571570
TI  - Should patients with GERD be screened once at least for Barrett's epithelium?
      Con: Patients with GERD should be screened once at least for Barrett's esophagus-
      medicine or magic?

PMID- 15571571
TI  - Should patients with GERD be screened once at least for Barrett's epithelium? A
      balancing view: To screen or not to screen: scoping out the issues.

PMID- 15571572
TI  - Meta-analysis: Can we mix apples and oranges?

PMID- 15571573
TI  - Reflections on medical practice: humanity lost.

PMID- 15571574
TI  - Long-term follow-up after pneumatic dilation for achalasia cardia: factors
      associated with treatment failure and recurrence.
AB  - BACKGROUND: Though most patients with achalasia cardia (AC) respond to pneumatic
      dilation (PD), one-third experienced recurrence. Long-term follow-up studies on
      factors associated with various outcomes are scanty. METHODS: In this
      retrospective study, 126 patients (36.5 +/- 14.6 yr, 76 male) with AC (diagnosed
      by esophagoscopy, barium esophagogram, and/or manometry) were followed up in
      person or through mail. The median dysphagia-free duration was calculated by
      Kaplan-Meier analysis. Factors associated with nonresponse and recurrence after
      PD were determined using univariate and multivariate analyses. RESULTS: Symptoms
      were dysphagia (126, 100%), chest pain (21, 17%), regurgitation (61, 48%), weight
      loss (33, 26%), and pulmonary symptoms (23, 18%); 5 of 126 (4%) had megaesophagus
      (> or =7 cm). The mean lower esophageal sphincter (LES) pressure was 38.7 +/-
      16.8 mmHg. One hundred and fifteen of 126 (91%) patients responded to PD (90
      (71%) to first session); 25 of these had recurrence of dysphagia after 15 +/- 17
      months. Post-PD chest pain requiring hospitalization occurred in 21 of 126 (17%;
      one had an esophageal perforation). Post-PD LES pressure, which was assessed in
      48 of 126 patients, had decreased by >50% from baseline in 14 of 29 responders, 0
      of 11 nonresponders (p= 0.004, chi(2) test), and 5 of 8 relapsers. The median
      dysphagia-free duration by Kaplan-Meier analysis was 60 months (SE 2.7, 95% CI
      54.7-65.3). On univariate analysis, male gender, pulmonary symptoms (nocturnal
      coughing spell, history of respiratory infection), absence of chest pain, and
      failure to achieve a reduction in LES pressure >50% after PD were associated with
      poor outcome; whereas age, grade of dysphagia, regurgitation, megaesophagus, and
      LES pressure before PD were not. Male gender was associated with poor outcome by
      multivariate-analysis. CONCLUSIONS: PD is an effective and safe treatment for AC.
      Post-PD LES pressure measurement may be helpful in assessing response. Male
      patients have poorer outcomes following PD.

PMID- 15571575
TI  - Clinical impact of upper endoscopy in the management of patients with
      gastroesophageal reflux disease.
AB  - OBJECTIVE: Esophago-gastro-duodenoscopy (EGD) is frequently performed in patients
      with heartburn. However, the benefit of an EGD is unclear. The objective is to
      determine the clinical impact of performing an EGD in the management of GERD.
      METHODS: Patients with alarm symptoms or persistent heartburn from primary care
      and gastroenterology clinics were invited to participate. Patients with known
      reflux complications or an EGD procedure within 3 yr were excluded. Endpoints for
      EGD-improving management were prospectively defined: change in medical therapy,
      dilating esophageal stricture, identifying Barrett's esophagus (BE), finding
      severe esophagitis (Hetzel-Dent grade 3 or 4), or finding cancer. RESULTS: Two
      hundred and six patients (59 M/147 F; median age, 48 yr) were enrolled, in which,
      124 had alarm symptoms and 82 had persistent heartburn. EGD improved the overall
      management in 40% of patients with alarm symptoms and 29% with persistent
      heartburn (p= NS). Medical therapy was altered in only 5% of patients, and no
      cancer was identified. EGD was more likely to improve management in males with
      alarm symptoms. CONCLUSIONS: It was uncommon for an EGD to alter antireflux
      therapy. The management was improved in approximately one-third of the patients
      by dilating esophageal stricture, finding BE to initiate surveillance, or finding
      severe esophagitis. EGD should be performed when alarm symptoms are present,
      especially in males.

PMID- 15571576
TI  - Characteristics and clinical relevance of proximal esophageal pH monitoring.
AB  - OBJECTIVE: It is well established that various ENT disorders and symptoms may be
      a manifestation of gastroesophageal reflux disease (GERD). Measuring proximal
      esophageal acid exposure might be useful in the evaluation of patients with
      suspected reflux-related ENT manifestations, but the limited available data are
      conflicting. The aim of the present study was to study the determinants of
      proximal esophageal acid exposure (PR) and to evaluate the clinical usefulness of
      ambulatory proximal pH monitoring. METHODS: Twenty healthy controls and 346
      patients with suspected reflux disease underwent typical and atypical GERD
      symptom assessment, endoscopy, esophageal manometry and ambulatory combined dual
      esophageal pH, and Bilitec duodeno-gastro-esophageal reflux exposure (DGER)
      monitoring. The presence of pathological PR and its relation to symptom pattern
      and distal esophageal acid exposure (DR) and DGER exposure were analyzed.
      RESULTS: Fifty-seven patients (16%) had pathological PR. Demographic
      characteristics, symptom pattern, and manometric findings did not differ in
      patients with normal or pathological PR. Patients with pathological PR had
      significantly higher DR and DGER. The multivariate analysis identified only
      pathological DR as an independent risk factor for the presence of pathological PR
      (odds ratio 4.515, 95% CI 2.48-8.23, p < 0.0001). Only 20 patients (6%) had
      pathological proximal reflux without pathological distal acid reflux. CONCLUSION:
      The findings of the present article do not support routine proximal esophageal pH
      monitoring as a clinical tool: PR does not differentiate patients with typical or
      atypical GERD manifestations and depends mainly on DR.

PMID- 15571577
TI  - Is routine ileoscopy useful? An observational study of procedure times,
      diagnostic yield, and learning curve.
AB  - BACKGROUND: IIeoscopy is not routinely attempted because of its perceived
      technical difficulty, time constraints, and the expectation of a low diagnostic
      yield. AIMS: To investigate the value of routine ileoscopy as an integral part of
      colonoscopy in terms of additional diagnostic information, extra time spent, and
      the relationship between ileoscopy rate and accumulation of colonoscopic
      experience. METHODS: We examined colonoscopy data from September 1995 to April
      2004 of a gastroenterological firm. Crude and adjusted total colonoscopy rates
      (CTCR, ATCR) and ileoscopy rate (IR) were calculated. For calculation of ATCR and
      IR, 108 procedures in patients with previous colonic resection and 91 with
      unavoidable reasons for failure to reach cecum were excluded. Time trend in
      ileoscopy rate was analyzed with IR as a function of cumulative colonoscopy
      experience. Data on procedure times were collected for 1,222 consecutive
      colonoscopies between November 2000 and April 2004. Sixty-three procedures in
      patients with previous colonic resection, and 47 unavoidable and 14 avoidable
      failures to reach cecum were excluded from analysis of procedure times. RESULTS:
      Of 2,537 colonoscopies, 1,902 were performed by a single consultant and 635 by
      eight trainees with or without assistance from the consultant. The CTCR, ATCR,
      and IR were 94%, 97.5%, and 71.5% respectively. IR and ATCR rose progressively to
      plateau at 85% and 99% after 600 and 750 procedures respectively. The diagnostic
      yield from ileoscopy and ileal histology was 16.7% and 19% in patients with
      colonic inflammatory bowel disease, and 2.69% and 7.4% in other patients. Twenty
      six ileoscopies in 24 patients showed Crohn's ileitis with normal colon. The
      other diagnoses were NSAID related or nonspecific ileitis, ileal lipoma, ileal
      villous atrophy, and amyloidosis. The median anus to cecum and cecum to ileum
      times were 8.5 and 2 minutes (interquartile ranges=5.5 to 14 and 1 to 4 minutes)
      respectively. Procedure times for colonoscopies involving trainees were
      significantly longer compared with those by the consultant alone (median anus to
      cecum and cecum to ileum times=16.5 v 7 and 2.5 v 1.5 minutes; p<0.0001 and 95%
      CI for difference=7.5 to 9 and 0.5 to 1 minutes respectively). The median length
      of ileum examined was 15 cms (IR=10-20 cms). CONCLUSIONS: IIeoscopy is the gold
      standard in the documentation of completeness of colonoscopy. With practice, it
      can be achieved routinely in at least 85% of colonoscopies. In skilled hands, it
      adds only 3 minutes to the procedure time, and contributes significantly to
      quality assurance and diagnostic yield.

PMID- 15571578
TI  - Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for
      difficult bile duct stones.
AB  - BACKGROUND: Choledocholithiasis and intrahepatic bile duct stones pose a
      significant health hazard, especially in the elderly. The large stone not
      removable with conventional endoscopic techniques, can be effectively and safely
      managed with electrohydraulic lithotripsy (EHL). METHODS: This study is a
      retrospective review of consecutive patients at the Wellesley Central Hospital
      and St. Michael's Hospital, who underwent peroral endoscopic fragmentation of
      bile duct stones with EHL under direct cholangioscopic control using a "mother
      baby" endoscopic system between October 1990 and March 2002. RESULTS: To date,
      111 patients have been analyzed. Of the 111 patients reviewed, 94 patients have
      had complete records and were included in this study. Mean follow-up was 26.2
      months (range 0-80). Prior to EHL, 93 of 94 patients (99%) had endoscopic
      retrograde cholangiopancreatography (ERCP) and failed standard stone extraction
      techniques (mean 1.9 ERCPs/patient, range 0-5). Indications for EHL were large
      stones (81 patients) or a narrow caliber bile duct below a stone of average size
      (13 patients). Successful fragmentation (61 complete, 28 partial) was achieved in
      89 of 93 patients (96%) (1 patient was excluded from analysis due to a broken
      endoscope). Fragmentation failures were due to targeting problems (2 patients)
      and hard stones (2 patients). Seventy-six percent of patients required 1 EHL
      session, 14% required 2 sessions, and 10% required 3 or more. All patients with
      successful stone fragmentation required post-EHL balloon or basket extraction of
      fragments. Complications included: cholangitis and/or jaundice (13 patients);
      mild hemobilia (1 patient); mild post-ERCP pancreatitis (1 patient); biliary leak
      (1 patient); and bradycardia (1 patient). There were no deaths related to EHL.
      Final stone clearance was achieved in 85 of 94 patients (90%). CONCLUSIONS: EHL
      via peroral endoscopic choledochoscopy is a highly successful and safe technique
      for use in the management of difficult choledocholithiasis and intrahepatic
      stones. This study has shown a stone fragmentation rate of 96% (89 of 93
      patients), and a final stone clearance rate of 90% (85 of 94 patients).

PMID- 15571579
TI  - Factors predictive of malignancy and endoscopic resectability in ampullary
      neoplasia.
AB  - OBJECTIVE: Endoscopic treatment of ampullary lesions has been well described,
      though it remains uncertain if specific features predict malignancy, and whether
      identifiable factors are associated with successful endoscopic resection of
      benign lesions. METHODS: Fifty-six consecutive patients undergoing endoscopic
      evaluation of ampullary neoplasia between March 2000 and May 2004 were included
      in the study. Clinical presentation, underlying medical conditions, endoscopic
      treatment, endoscopic ultrasound (EUS) to define extent of local involvement,
      pathology results, and outcome were documented. Data elements for analysis
      included EUS findings, lesion lifting with submucosal injection, age, gender,
      tumor size, and endoscopic intervention. Analyses were performed to determine the
      ability to predict malignancy and the ability to extirpate benign lesions.
      RESULTS: Thirty-one males and 25 females were included; mean age was 62 yr. Final
      diagnoses included 29 adenomas, 20 adenocarcinomas, 4 adenomyomas, 2
      paragangliomas, and 1 neuroendocrine tumor. Thirty of 35 patients with benign
      lesions had extirpation with a mean of two endoscopic procedures. Complications
      of endoscopic resection included cholangitis (1), bleeding (2), and pancreatitis
      (4). The presence of malignancy was associated by multivariate analysis with the
      inability to obtain a cleavage plane with saline injection. Univariate analysis
      also identified EUS T stage as a predictor of malignancy. In benign lesions, none
      of the analyzed variables predicted successful endoscopic resection. CONCLUSION:
      In ampullary lesions, failure to achieve a cleavage plane with submucosal
      injection is the strongest predictor of malignancy followed by EUS T stage.
      Endoscopic treatment of benign ampullary neoplasia is effective; no factor was
      predictive of successful extirpation.

PMID- 15571580
TI  - Endoscopic balloon dilation of ileal pouch strictures.
AB  - BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis is the
      surgical treatment of choice in patients with ulcerative colitis. Strictures can
      occur at the inlet and outlet of the pouch. Endoscopic balloon dilation has been
      successfully used in patients with Crohn's strictures at the small intestine and
      colon. There are no published trials on endoscopic balloon therapy of ileal pouch
      strictures. AIM: To evaluate outpatient endoscopic balloon dilation of strictures
      in ileal pouches. METHODS: Patients underwent nonfluoroscopy-guided, nonsedated,
      outpatient endoscopic dilations with an 8.6-mm upper endoscope and through-the
      scope balloons (size: 11-18 mm). Pre- and posttreatment Pouchitis Disease
      Activity Index symptom scores (range: 0-6), endoscopic stricture scores based on
      resistance in passing the endoscope (range: 0-4), and Cleveland Global Quality of
      Life were compared. RESULTS: Nineteen patients with pouch strictures who had
      concurrent Crohn's disease of the pouch (n = 11), cuffitis (n = 5), and pouchitis
      (n = 3), including 14 inlet and 14 outlet strictures, were enrolled. The mean
      number of strictures for each patient was 1.61 +/- 0.78. All strictures were
      successfully dilated with the through-the-scope balloon, with a mean of 1.74 +/-
      1.19 (range: 1-5) sessions for each patient. Nine patients had a second endoscopy
      at 8 wk and five patients had a third pouch endoscopy at 16 wk after the initial
      endoscopic dilation. Endoscopic stricture scores immediately (0.30 +/- 0.47), 8
      wk (0.40 +/- 0.51), and 16 wk (0.44 +/- 0.76) after the dilation were
      significantly improved compared to the predilation stricture scores (2.67 +/-
      0.78). The symptom scores and quality-of-life (QOL) scores improved at week 8 and
      16 following dilation, with a mean follow-up of 6.10 +/- 5.83 months (2-25
      months). No complications were experienced with the procedure. One patient with
      CD who failed endoscopic and medical therapy underwent pouch resection.
      CONCLUSION: In conjunction with medical therapy, outpatient endoscopic balloon
      dilation appears safe and effective in treating pouch inlet and outlet
      strictures, by relieving symptoms, restoring pouch patency, and improving QOL in
      the majority of patients.

PMID- 15571581
TI  - Pilot studies of single and combination antiretroviral therapy in patients with
      primary biliary cirrhosis.
AB  - OBJECTIVE: Preliminary reports suggest that patients with primary biliary
      cirrhosis (PBC) have evidence of human betaretrovirus infection. The aim of this
      study was to determine whether antiviral therapy impacts on the disease process.
      METHODS: We conducted two consecutive open-labeled, nonrandomized, 1-yr pilot
      studies; the first with lamivudine 150 mg/day and the second with Combivir
      combination therapy using lamivudine 150 mg and zidovudine 300 mg twice a day.
      Eleven PBC patients enrolled in each study, seven patients were entered into both
      studies, and one patient was withdrawn from each study due to side effects.
      RESULTS: Evaluation of liver biopsies before and after lamivudine therapy showed
      a 4-5 increase in necroinflammatory score, a 1-1.5 elevation in bile duct injury,
      with little change in the percentage of portal tracts with bile ducts (50-52%).
      None of the patients in the lamivudine study normalized alkaline phosphatase.
      Histological assessment following Combivir therapy revealed a 6 to 4 improvement
      in necroinflammatory score (p < 0.03, 95% CI: 0.53-2.33), a 3 to 1 reduction in
      bile duct injury (p < 0.02, 95% CI: 1.08-2.07), and a 45-75% increase in portal
      tracts with bile ducts (p < 0.05, 95% CI: 0.02-0.29). In the Combivir cohort,
      five patients normalized alkaline phosphatase and four developed normal AST, ALT,
      and alkaline phosphatase. CONCLUSIONS: Histological and biochemical endpoints
      were achieved in the Combivir pilot study suggesting a larger placebo-controlled
      trial is required as a proof of principle to assess whether antiviral therapy
      impacts the PBC disease process.

PMID- 15571582
TI  - Apocalypsal versus apocryphal: the role of retroviruses in primary biliary
      cirrhosis.
AB  - The etiology of primary biliary cirrhosis (PBC), much like that of other
      autoimmune diseases, remains enigmatic. In the case of PBC, several candidates
      have been proposed, including bacteria, chemicals, and retroviruses. The support
      for a retroviral etiology has led to a pilot therapeutical interventional
      program. However, there is limited objective data which can be used to support
      such a thesis. Until reproducible and mechanistically sound data can be offered,
      we suggest that pharmaceutical trials are unrealistic and should be discouraged.

PMID- 15571583
TI  - A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced
      liver disease nonresponsive to antiviral therapy.
AB  - OBJECTIVES: To evaluate the effects of recombinant human interleukin (rhIL)-11 on
      liver histology in patients with chronic hepatitis C virus (HCV) infection and
      advanced liver disease who had failed antiviral therapy. METHODS: This was an
      open-label study of rhIL-11 (Neumega), Wyeth Laboratories, Collegeville, PA) at a
      dose of 5 microg/kg administered by subcutaneous injection daily for 12 wk. The
      primary efficacy endpoint was the change in the Knodell Histology Activity Index
      (HAI) between pre- and posttreatment liver biopsies. Secondary efficacy endpoints
      included changes in plasma alanine transaminase (ALT) concentrations and in the
      number of platelets. RESULTS: The Knodell HAI improved in 11 (55%) of the 20
      subjects enrolled, with the mean score improving from 7.3 to 5.9 (p= 0.006).
      Eight subjects (40%) experienced significant improvement as defined by a decrease
      of at least two points in the HAI. IL-11 treatment was also associated with a
      decrease in ALT levels from a mean level of 113 IU/L at baseline to 65 IU/L at
      week 12 (p < 0.001). Platelet levels increased from a mean of 143 x 10(3)/microl
      at baseline to 198 x 10(3)/mul at week 12 of treatment (p < 0.001). Overall, rhIL
      11 was well tolerated and no serious adverse events (AEs) were reported. The most
      common AE was edema of the lower extremities, which occurred in all subjects.
      CONCLUSIONS: The findings from this pilot study suggest that rhIL-11 may be
      beneficial for patients with hepatic inflammation and advanced liver disease
      associated with chronic HCV infection. Larger clinical trials are warranted to
      further evaluate the long-term antiinflammatory and antifibrotic effects of rhIL
      11.

PMID- 15571584
TI  - A pilot trial of pentoxifylline in nonalcoholic steatohepatitis.
AB  - OBJECTIVES: Tumor necrosis factor alpha (TNF alpha) contributes to liver damage
      and insulin resistance among patients with nonalcoholic steatohepatitis (NASH).
      Pentoxifylline inhibits TNF alpha production. We therefore conducted a 12-month
      pilot trial to assess the efficacy and safety of pentoxifylline (1,600 mg/day)
      among 20 patients with NASH. METHODS: Patients had biopsy-confirmed NASH with
      other causes of liver disease and secondary causes of NASH excluded. Patients who
      drank more than 40 gm of ethanol weekly were also excluded. Pentoxifylline (400
      mg q.i.d.) was given for 12 months. Liver enzymes and adverse events were
      monitored every 3 months until completion. RESULTS: The 20 patients had a mean
      age of 50 +/- 11 yr. Eleven (55%) were female, 14 were obese (body mass index >
      or =30 kg/m(2)), and 7 (35%) were diabetic. At baseline, median steatosis grade
      was 2 (range 1-3), median necroinflammatory grade was 1 (1-2), and median
      fibrosis stage was 2 (0-4). Nine patients withdrew from the study, primarily
      because of nausea. No serious adverse events occurred. Alanine and aspartate
      aminotransferase levels were significantly lower at 12 months compared to
      baseline (84 +/- 64 vs 138 +/- 76, p= 0.002 and 58 +/- 37 vs 102 +/- 62, p=
      0.003, respectively). Bilirubin did not change significantly from baseline (0.8
      +/- 0.4 vs 0.8 +/- 0.3, p= 0.95), nor did alkaline phosphatase (193 +/- 68 vs 180
      +/- 53, p= 0.62) or albumin (4.0 +/- 0.2 vs 4.2 +/- 0.3, p= 0.41). CONCLUSIONS:
      Aminotransferase levels among patients with NASH improve with administration of
      pentoxifylline. Strategies to overcome side effects will be needed for future
      trials.

PMID- 15571585
TI  - Prophylactic lamivudine administration prevents exacerbation of liver damage in
      HBe antigen positive patients with hepatocellular carcinoma undergoing
      transhepatic arterial infusion chemotherapy.
AB  - BACKGROUND AND AIMS: Exacerbation of liver damage during transhepatic arterial
      infusion chemotherapy (THAIC) is a critical complication in patients with
      hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). We previously
      reported that HBe antigen positivity was the associating factor for the
      exacerbation of liver damage. In the present study, we investigated the effect of
      lamivudine administration for exacerbation of liver damage in such patients.
      PATIENTS AND METHODS: Seventeen patients with HBV-related hepatocellular
      carcinoma who received THAIC were reviewed. Eight of these patients received
      lamivudine administration. Nine patients did not receive lamivudine
      administration. All patients were HBe antigen positive. Liver function tests,
      liver enzymes, HBV-DNA levels, HBe antigen, HBe antibody, and mutation in the
      precore and core-promoter regions of HBV DNA were evaluated. RESULTS: In the
      lamivudine-treated group, HBV-DNA levels were significantly reduced and did not
      increase throughout chemotherapy. Lamivudine did not induce any changes in
      precore or core-promoter regions. Although levels of alanine aminotransferase
      (ALT), asparate aminotransferase (AST), total bilirubin, and prothrombin time
      (PT) in the lamivudine-treated group did not change, levels of ALT, AST and total
      bilirubin increased, and PT were prolonged in the untreated group by
      chemotherapy. No patients receiving lamivudine administration showed exacerbation
      of liver damage. Exacerbation of liver damage was detected in six patients
      without lamivudine administration. Of these, three patients died of progressive
      liver failure due to reactivation of HBV. CONCLUSION: These results indicate that
      prophylactic lamivudine administration reduces HBV-DNA levels and prevents
      exacerbation of liver damage throughout the period of chemotherapy in HBe antigen
      positive patients with hepatocellular carcinoma.

PMID- 15571586
TI  - Sero-reactivity to microbial components in Crohn's disease is associated with
      disease severity and progression, but not NOD2/CARD15 genotype.
AB  - BACKGROUND AND AIMS: Antibodies directed against the porin protein C of
      Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently
      been described in Crohn's disease (CD). Those directed against Saccharomyces
      cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been
      more widely studied and may be of diagnostic importance. We aimed to assess the
      frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD
      cohort, establish phenotypic associations, and compare with a U.S. cohort.
      METHODS: One hundred and forty-two well-characterized CD patients (76 females,
      median age 39 yr (17-88)) were studied. CD was classified by the Vienna
      classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele
      specific primers were used for NOD2/CARD15 genotyping. RESULTS: Anti-OmpC, anti
      I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD
      patients, respectively. Multivariate analysis demonstrated independent
      associations of anti-OmpC to be progression of disease type (p= 0.005) and long
      disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p=
      0.002) and the need for surgery (p= 0.033). ASCA were associated with disease
      progression (p < 0.001). When the presence and magnitude of all antibody
      responses were considered, reactivity to microbial components was associated with
      long disease duration (p < 0.001), progression of disease type (p < 0.001),
      penetrating disease (p= 0.008), small bowel disease (p < 0.02), and the need for
      surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15
      genotype. CONCLUSION: Reactivity to microbial components is associated with
      severe CD characterized by small bowel involvement, frequent disease progression,
      longer disease duration, and greater need for intestinal surgery.

PMID- 15571587
TI  - Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's
      disease and rheumatoid arthritis.
AB  - OBJECTIVES: Infliximab is approved for the treatment of rheumatoid arthritis (RA)
      and Crohn's disease (CD). We report the first large series of pregnancy outcomes
      in women with RA and CD exposed to infliximab. METHODS: The infliximab safety
      database was queried for all reports of pregnancy. Data were extracted regarding
      the indication for infliximab, timing of infliximab relative to conception,
      pregnancy course, and pregnancy outcome. The proportion of live births,
      miscarriages, and therapeutic terminations for women directly exposed to
      infliximab before or during confirmed pregnancy were compared to those expected
      for the general U.S. population of pregnant women and pregnant women with CD not
      exposed to infliximab. RESULTS: Of the 146 identified pregnancies, 131 involved
      women exposed directly to infliximab and outcome data were available for 96 of
      these women. Live births occurred in 67% (64/96), miscarriages in 15% (14/96),
      and therapeutic termination in 19% (18/96) of the pregnancies directly exposed to
      infliximab with available outcome data. These results are similar to those
      expected for the general U.S. population of pregnant women or pregnant women with
      CD not exposed to infliximab. CONCLUSION: Data from the infliximab safety
      database suggest that infliximab exposure during pregnancy results in outcomes
      that do not differ from those in the U.S. population of pregnant women and
      pregnant women with CD not exposed to infliximab. No increased risk of adverse
      outcome was detected, however, follow-up of larger numbers of pregnant women
      exposed to infliximab will be necessary to definitively exclude any fetal risk.

PMID- 15571588
TI  - Differential effects of NOD2 variants on Crohn's disease risk and phenotype in
      diverse populations: a metaanalysis.
AB  - OBJECTIVES: Three variants of the CARD15/NOD2 gene (SNP8, SNP12, and SNP13) have
      been associated with Crohn's disease (CD). We assessed the impact of NOD2
      variants on the CD risk across diverse populations and examined possible
      associations with disease phenotype. METHODS: We performed a metaanalysis
      searching MEDLINE and EMBASE (last search 05/2004) and contacting field experts.
      RESULTS: Forty-two eligible studies contributed data on 206 comparisons. No
      variants were detected in Asians. In non-Jewish descent Caucasians carriage of
      SNP8, SNP12, or SNP13 had an odds ratio (OR) for CD of 2.20 (95% CI: 1.84-2.62),
      2.99 (95% CI: 2.38-3.74), and 4.09 (95% CI: 3.23-5.18), respectively. For Jewish
      descent patients the corresponding ORs were 1.74, 1.93, and 2.45, respectively.
      The OR in carriers of at least two alleles was 17.1 (95% CI: 10.7-27.2). Large
      studies tended to yield more conservative estimates than smaller studies, so
      publication or other bias cannot be excluded. Among CD patients, carrying at
      least one high-risk variant increased slightly the risk for familial disease (OR
      = 1.49, (95% CI: 1.18-1.87)), modestly the risk of stenosing CD (OR = 1.94, (95%
      CI: 1.61-2.34)), and more prominently the risk of small bowel involvement (OR =
      2.53, (95% CI: 2.01-3.16)). CONCLUSIONS: SNP8, SNP12, and SNP13 have differential
      effects on CD risk, with SNP13 having the strongest genetic effect. These NOD2
      variants are also significant risk factors for CD phenotype, in particular ileal
      location.

PMID- 15571589
TI  - Ambulatory 24-hour colonic manometry in slow-transit constipation.
AB  - BACKGROUND: The colonic neuromuscular dysfunction in patients with constipation
      and the role of colonic manometry is incompletely understood. AIM: To study
      prolonged colonic motility and assess its clinical significance. METHODS: Twenty
      four-hour ambulatory colonic manometry was performed in 21 patients with slow
      transit constipation and 20 healthy controls by placing a 6-sensor solid-state
      probe up to the hepatic flexure. Quantitative and qualitative manometric analysis
      was performed in 8-h epochs. Patients were followed up for 1 yr. RESULTS:
      Constipated patients showed fewer pressure waves and lower area under the curve
      (p < 0.05) than controls during daytime, but not at night. Colonic motility
      induced by waking or meal was decreased (p < 0.05) in patients. High-amplitude
      propagating contractions (HAPCs) occurred in 43% of patients compared to 100% of
      controls and with lower incidence (1.7 vs 10.1, p < 0.001) and propagation
      velocity (p < 0.04). Manometric features suggestive of colonic neuropathy were
      seen in 10, myopathy in 5, and normal profiles in 4 patients. Seven patients with
      colonic neuropathy underwent colectomy with improvement. The rest were managed
      conservatively with 50% improvement at 1 yr. CONCLUSIONS: Patients with slow
      transit constipation exhibited either normal or decreased pressure activity with
      manometric features suggestive of colonic neuropathy or myopathy as evidenced by
      absent HAPC or attenuated colonic responses to meals and waking. In refractory
      patients, colonic manometry may be useful in characterizing the underlying
      pathophysiology and in guiding therapy.

PMID- 15571590
TI  - Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy
      or endoscopic sphincterotomy.
AB  - OBJECTIVES: To determine the prevalence of recurrence of gallstone pancreatitis,
      its clinical features, and the presence of prognostic factors of recurrence.
      METHODS: From January 1, 2000 to August 31, 2003, 233 patients admitted with
      acute gallstone pancreatitis (AGP) were prospectively studied. Patients were
      divided into two groups: recurrent and nonrecurrent group. Clinical, analytical,
      radiological, prognostic parameters, and severity (Atlanta criteria) were
      assessed, along with the performance of cholecystectomy or endoscopic
      sphincterotomy (ES). Clinical features of recurrence were analyzed. Univariate
      (chi(2), Student's t-test) and multivariate tests were performed. Statistical
      significance was assumed if p < 0.05. RESULTS: Two hundred and eighty-six attacks
      were identified. Forty-two patients (18.2%) recurred, suffering 53 recurrent
      attacks, which took place within 30 days in 23.3%. Patients who did not undergo
      surgery after the first attack had 31-fold risk of recurrence (OR = 31.5%, CI =
      95%[7.22-137.84], p < 0.001). In patients not operated, recurrence was more
      frequent if ES was not performed (37.04%vs 0%, p= 0.019). Among patients with
      surgical risk, none who recurred underwent ES, compared with 27.9% of those who
      did not recur. Patients in the nonrecurrent group underwent cholecystectomy
      within the first 30 days or ES more frequently (31.2%vs 7.3%, p= 0.001).
      CONCLUSIONS: Recurrence of gallstone pancreatitis is a frequent event. Delay of
      cholecystectomy implies an increased risk of recurrence. ES could be an
      acceptable option to prevent recurrence in patients who are not candidates for
      surgery or who do not desire to undergo cholecystectomy.

PMID- 15571591
TI  - Detection of cardia intestinal metaplasia: do the biopsy number and location
      matter?
AB  - BACKGROUND AND AIM: Presence of intestinal metaplasia in the gastric cardia
      (cardia intestinal metaplasia, CIM) has been reported in 5-34% of patients
      undergoing upper endoscopy and is a topic of interest given the rising incidence
      of cancer in this location. The aim of this article is to determine the
      prevalence of CIM in biopsies obtained from two separate locations within the
      gastric cardia. METHODS: Patients presenting to the endoscopy unit for upper
      endoscopy for any symptoms were invited to participate in the study. The biopsy
      protocol included: eight biopsies from the gastric cardia, four from upper cardia
      (forceps across the squamocolumnar junction), four from lower cardia (within 1 cm
      of upper cardia), and four each from the gastric body and antrum. All cardia
      biopsies were stained with hematoxylin and eosin (H&E) and alcian blue at pH 2.5
      for the presence of goblet cells and the body/antrum biopsies were stained with
      Steiner silver stain for Helicobacter pylori detection. In patients testing
      negative for H. pylori by histology, a serology test was performed. RESULTS:
      Sixty-five patients have been evaluated by this protocol; median age 54 yr
      (range: 34-81 yr), 63 males, 53 Caucasians, and 12 African Americans. The
      detection of CIM was as follows: upper cardia only, 7, both upper and lower
      cardia, 5, and lower cardia only, 7. Thus, CIM was detected in 12 patients (18%)
      in the upper cardia biopsies, in 12 patients (18%) in the lower cardia; overall
      prevalence of CIM was 29% (19 patients). Fifty-eight percent of CIM patients
      tested positive for H. pylori by either histology or serology. The addition of
      serology allowed for the detection of eight additional H. pylori-positive CIM
      patients. CONCLUSIONS: The prevalence of CIM in this study was similar (18%, four
      biopsies) at each location; however, if both locations were considered (eight
      biopsies), the prevalence increased to 29%. Thus, CIM prevalence may vary
      depending on the number of biopsies obtained as well as on the location of
      biopsies. Use of additional testing detects more patients who are H. pylori
      positive and should be performed if association of CIM with H. pylori is
      contemplated. Future endoscopic studies of the gastric cardia should specify the
      location of biopsies, the number of biopsies obtained, and the tests used to
      diagnose H. pylori.

PMID- 15571592
TI  - Gut transit in celiac disease: delay of small bowel transit and acceleration
      after dietary treatment.
AB  - OBJECTIVES: New studies indicate that body mass index (BMI) may influence gut
      transit. We studied gut transit and BMI in patients with celiac disease before
      and after treatment. METHODS: Twenty-seven (16 female) patients with untreated
      celiac disease were included for detailed gastrointestinal transit measurement
      and calculation of BMI. Ten patients (5 female) were also studied after dietary
      treatment. A newly developed radiological transit procedure was used. Eighty
      three healthy subjects were used as controls. RESULTS: In untreated male patients
      BMI was significantly reduced compared to healthy males, and small bowel transit
      time (SBTT) was significantly longer compared with healthy males, 3.9 (1.2-5.5)
      versus 2.5 h (1.4-4.3), median and percentile 10 and 90, respectively, and p=
      0.04. In the 10 men and women with repeated measurements, BMI increased
      significantly and small bowel transit accelerated after treatment and was 3.6 h
      (1.7-5.5) before treatment and 2.3 h (0.7-4.0) after treatment, and p= 0.007. In
      women, BMI did not differ significantly between untreated patients and healthy
      subjects, and 31% of the female patients were overweight. Small bowel transit was
      significantly faster in untreated female patients who were overweight compared
      with lean female patients. CONCLUSION: Small bowel transit seems to be delayed in
      lean patients with untreated celiac disease. BMI may have some influence on the
      variations of small bowel transit before and after treatment.

PMID- 15571593
TI  - Celiac disease and the transition from childhood to adulthood: a 28-year follow
      up.
AB  - OBJECTIVES: Follow-up of celiac disease diagnosed in childhood is variable or
      nonexistent after transition to adulthood. Outcome, continuity of care, and
      adherence to a gluten-free diet are poorly documented. We report a 28-yr follow
      up of 50 adults in whom the original childhood diagnosis could be confirmed.
      METHODS: Original pediatric charts were reviewed, and subjects were invited to
      undergo dietary evaluation, measurement of bone mineral density, and quality-of
      life assessment. The mean duration of celiac was 28.5 yr, median 28.7 yr (range
      22-45 yr). The mean and median age of the group was 35 yr. RESULTS: Only 22% of
      patients were enrolled in an adult gastroenterology clinic. Fifty percent were
      fully compliant with a gluten-free diet; 18% were partially compliant; and 32%
      were not adhering to diet. The main motivating factor for dietary compliance was
      avoidance of symptoms rather than avoidance of complications. Eighty-six percent
      of the females and 21% of the males had iron deficiency. Bone mineral density was
      subnormal in 32%; 28.9% were osteopenic and 2.6% were osteoporotic. Quality-of
      life scores were normal. CONCLUSIONS: Most patients diagnosed with celiac in
      childhood receive no medical or dietary supervision after transition to
      adulthood. One-third are not compliant with diet; the primary motivating factor
      for those who do comply is avoidance of symptoms rather than fear of
      complications. The prevalence of preventable and treatable disorders in these
      young adults highlights a failure of health services after transition from
      pediatric to adult health care.

PMID- 15571594
TI  - Increased somatic complaints and health-care utilization in children: effects of
      parent IBS status and parent response to gastrointestinal symptoms.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) runs in families. The aims of this
      study were (i) to exclude biased perception by a mother with irritable bowel as
      the explanation for increased gastrointestinal (GI) symptoms in their children,
      (ii) to determine whether non-GI as well as GI symptoms run in families, and
      (iii) to determine whether parent IBS status and solicitous responses to illness
      exert independent effects on children's symptom reports, medical clinic visits,
      and school absences. METHODS: Two hundred and eight mothers with irritable bowel
      and their 296 children (cases: average age 11.9 yr; 48.6% male) and 241
      nonirritable bowel mothers and their 335 children (controls: 11.8 yr; 49.0% male)
      were interviewed. Other factors assessed were stress, mother's and child's
      psychological symptoms, child's perceived competence, pain coping style, age, and
      sex. Children were interviewed apart from their parents. RESULTS: Case children
      independently reported more frequent stomach aches (F(591) = 9.22; p= 0.0025) and
      non-GI symptoms (F(562) = 21.03; p < 0.001) than control children. Case children
      also had more school absences (F(625) = 26.53; p < 0.0001), physician visits for
      GI symptoms (F(602) = 8.09; p= 0.005), and non-GI clinic visits (F(602) = 27.92;
      p < 0.001) than control children. Children whose mothers made solicitous
      responses to illness complaints independently reported more severe stomach aches
      (F(590) = 11.42; p < 0.001), and they also had more school absences for stomach
      aches (F(625) = 5.33; p < 0.05), but solicitous behavior did not significantly
      impact non-GI symptom reporting, clinic visits, or school absences. Differences
      between cases and controls remained significant after adjusting for potential
      moderators. CONCLUSIONS: (i) Frequent GI complaints in children whose mothers
      have irritable bowel are not explained by the mother's biased perceptions; (ii)
      children of mothers with irritable bowel have more non-GI as well as GI symptoms,
      disability days, and clinical visits; (iii) and parent IBS status and solicitous
      responses to illness have independent effects on the child's symptom complaints.

PMID- 15571595
TI  - The importance of multichannel intraluminal impedance in the evaluation of
      children with persistent respiratory symptoms.
AB  - OBJECTIVES: Previous evidence suggests an association between gastroesophageal
      reflux disease and chronic respiratory disease in children. Despite antisecretory
      antacid therapy, respiratory symptoms often persist supporting a role for nonacid
      reflux. The aim of this study was to determine whether nonacid reflux occurs in
      children with chronic respiratory disease. METHODS: Twenty-eight children (mean
      age: 6.5 +/- 5.6 yr) with persistent respiratory symptoms on antacid medications
      underwent 24 h pH/multichannel intraluminal impedance (pH/MII) recording. The
      symptom index (SI) and the symptom sensitivity index (SSI) were calculated for
      each patient. Logistic regression was performed to determine which reflux
      characteristics were associated with a high degree of symptom correlation present
      during the occurrence of symptoms. RESULTS: A total of 1,822 reflux episodes were
      detected by pH/MII, 45% of which were nonacidic. The mean SI increased using
      pH/MII (35.7 +/- 28.5) compared to pH probe alone (14.6 +/- 18.9; p= 0.002); no
      differences in the mean SSI using pH/MII compared to pH probe alone were
      identified. Significantly more patients had a positive SI using pH/MII than pH
      probe alone (p= 0.035); there was no difference in the number of patients with a
      positive SSI using pH/MII compared to pH probe alone. Multivariate analysis
      revealed that symptoms occurred more frequently when the reflux was nonacidic,
      mixed, and full column. Also, younger children were more likely to have the
      simultaneous occurrence of symptoms and reflux. CONCLUSIONS: Nonacid reflux may
      be an important predictor of respiratory symptoms. pH/MII provided important
      information in the evaluation of children with intractable respiratory symptoms.

PMID- 15571596
TI  - Interventions for treating collagenous colitis: a Cochrane Inflammatory Bowel
      Disease Group systematic review of randomized trials.
AB  - OBJECTIVES: To conduct a systematic review to determine effective treatments for
      patients with clinically active collagenous colitis. METHODS: Relevant articles
      were identified via the MEDLINE, PUBMED, and Cochrane Collaboration databases,
      manual searches of the references of identified articles, and review articles on
      collagenous or microscopic colitis, as well as searches of abstracts from major
      gastroenterological meetings. RESULTS: Five randomized trials assessing
      treatments for collagenous colitis were identified. One trial studying bismuth
      subsalicylate (nine 262 mg tablets daily for 8 wk) included 9 patients. Patients
      who received the bismuth preparation were more likely to have clinical (p= 0.003)
      and histological (p= 0.003) improvement than those who received placebo. In a
      trial comparing prednisolone (50 mg daily for 2 wk) to a placebo in 11 patients,
      a trend toward clinical response in patients on prednisone was reported (p=
      0.064). The effect of prednisolone on histological improvement was not studied. A
      total of 94 patients were enrolled in three trials studying budesonide (9 mg
      daily or in a tapering schedule for 6-8 wk). The pooled odds ratio for clinical
      response to treatment with budesonide was 12.32 (95% CI: 5.53-27.46). The NNT
      (number of patients needed to treat with budesonide to achieve 1 improved
      patient) was 2 patients. This therapy was well tolerated. There was significant
      histological improvement with treatment in all three trials studying budesonide
      therapy. CONCLUSIONS: There is strong evidence that budesonide is effective and
      well tolerated for the treatment of collagenous colitis. The evidence for benefit
      with bismuth subsalicylate or prednisolone is weaker. It is not clear that any of
      these agents produce actual remission, as opposed to clinical and histological
      improvement of the disease.

PMID- 15571597
TI  - Carcinoid tumors and fibrosis: an association with no explanation.
AB  - Carcinoid tumors are slow-growing neuroendocrine neoplasms most commonly
      associated with the gut and broncho-pulmonary system. In many instances, they are
      identified at surgery for unexplained bowel obstruction or during exploration of
      the small bowel in search of a primary tumor once distant metastases have been
      detected. Carcinoid tumors of the small bowel often present with pronounced
      fibrosis in the peri-tumoral tissues, distant in the heart or lungs, and locally
      in the peritoneal cavity. Despite medical and therapeutic advances that have
      alleviated symptoms and prolonged life, a substantial subset of patients develops
      mesenteric and small bowel carcinoid fibrosis and/or carcinoid heart disease.
      Fibrosis, and increasingly cardiac heart disease, are important components of
      intestinal carcinoid disease and are of considerable clinical concern, as both of
      these conditions reflect a connective tissue disorder whose etiology, biology,
      and therapy are unknown. In the past, individuals with carcinoid disease died of
      metastasis and uncontrollable symptomatology. Currently, there exists no clinical
      method to determine the development of fibrosis and little is understood about
      the biological basis of fibrosis. The elucidation of the biology and management
      of fibrosis is thus an issue of paramount clinical and scientific importance in
      determining appropriate diagnostic and therapeutic strategy. Therefore, the
      unraveling of the molecular events indicative of fibrosis in these cells and the
      identification of appropriate therapeutic targets is of considerable patient-care
      relevance. We have surveyed the world literature over the past 40 yr to evaluate
      both the incidence of carcinoid processes and track the evolving understanding of
      this process. In addition, we have provided more current mechanistic information
      in regard to the biological basis of fibrosis associated with small bowel
      carcinoid tumors.

PMID- 15571598
TI  - Liver disease in pregnancy.
AB  - Liver dysfunction during pregnancy can be caused by conditions that are specific
      to pregnancy or by liver diseases that are not related to pregnancy itself. This
      review attempts to summarize the epidemiology, pathophysiology, and management of
      the different pregnancy-related liver diseases, and to review different liver
      diseases not related to pregnancy and how they may affect or be effected by
      pregnancy. Some of the liver diseases specific to pregnancy can cause significant
      morbidity and mortality both to the mother and to the fetus, while most of the
      liver diseases not specific to pregnancy do not have a deleterious effect on the
      pregnancy itself.

PMID- 15571599
TI  - Initial management of acute pancreatitis: critical issues during the first 72
      hours.
AB  - Although most patients with acute pancreatitis have a mild course, almost a
      quarter of patients will develop complications. It has become clear that the
      early management of patients with acute pancreatitis will likely affect outcome.
      Too often patients are admitted to the hospital with what appears to be mild
      disease only later to deteriorate with severe disease. This review will focus on
      the early management of patients with acute pancreatitis in an attempt to prevent
      severe disease, complications, and death.

PMID- 15571600
TI  - Gastrointestinal angiodysplasia in a patient with type 2 von Willebrand's disease
      and analysis of exon 28 of the von Willebrand factor gene.
AB  - Although the association between gastrointestinal angiodysplasia and von
      Willebrand's disease has been suggested, molecular mechanisms involved in the
      formation of angiodysplasia in patients with von Willebrand's disease remained
      undetermined. We examined exon 28 of the von Willebrand factor gene in a patient
      with both von Willebrand's disease and recurrent bleeding from angiodysplasia in
      the duodenum as well as his father's, and found a point mutation, C 3916-->T
      (amino acid substitution; Arg 543-->Trp), in the A1 domain of the von Willebrand
      factor gene. This mutation was identical with a previously reported mutation in a
      patient with von Willebrand's disease complicated with gastrointestinal
      angiodysplasia.

PMID- 15571601
TI  - Proof of principal studies to assess the role of the human betaretrovirus in
      patients with primary biliary cirrhosis.

PMID- 15571602
TI  - Induction of interleukin-8 expression by Helicobacter pylori infection in
      patients with endoscopy-negative gastroesophageal reflux disease.

PMID- 15571605
TI  - Early intensive resuscitation of patients with upper gastrointestinal bleeding
      decreases mortality.

PMID- 15571606
TI  - Disseminated primary varicella after initiation of infliximab for Crohn's
      disease.

PMID- 15571607
TI  - The other mutation is found: follow-up of an exceptional family with Wilson
      disease.

PMID- 15571608
TI  - Antitransglutaminase antibodies and giardiasis.

PMID- 15571610
TI  - Discordance between beliefs and recommendations of gynecologic oncologists in
      ovarian cancer management.
AB  - PURPOSE: The purpose of this study was to determine how physician experts make
      decisions for clinical scenarios in ovarian cancer and describe a profile of
      factors reported to influence treatment decisions. METHODS: A questionnaire was
      sent to Full Members of the Society of Gynecologic Oncologists regarding surgery
      and chemotherapy for scenarios of primary and recurrent ovarian cancer. RESULTS:
      In a scenario of primary presentation, 94% of respondents chose a treatment of
      tumor resection over chemotherapy. Despite the preference for surgery in a
      clinical scenario, 50% agreed with a statement that neoadjuvant chemotherapy is
      equivalent to primary surgery. In a scenario of recurrent disease, a comparable
      number of respondents chose a treatment of secondary cytoreductive surgery (45%)
      versus direct retreatment with chemotherapy (49%). Those choosing surgery
      responded that they believed in extensive surgery to achieve optimal
      cytoreduction. Most (62%) respondents described themselves as collaborative in
      treatment planning, yet only 24% reported that patient preference strongly
      influences their decision making. CONCLUSIONS: Although a plan for primary
      cytoreduction is favored, in specific scenarios, views were divided for the role
      of neoadjuvant chemotherapy. For a recurrent disease scenario, support was
      divided between secondary cytoreductive surgery and direct retreatment with
      chemotherapy. Further clinical research is necessary to minimize the discordance
      between physician beliefs and recommendations.

PMID- 15571611
TI  - Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin.
AB  - To determine whether ginger had antiemetic effect in cisplatin-induced emesis, we
      conducted a randomized, double-blinded crossover study in 48 gynecologic cancer
      patients receiving cisplatin-based chemotherapy. Subjects were randomly allocated
      to regimen A or regimen B in their first cycle of the study. All patients
      received standard antiemetics in the first day of cisplatin administration. In
      regimen A, capsules of ginger root powder were given orally 1 g /day for 5 days,
      starting on the first day of chemotherapy. In regimen B, placebo was given on the
      first day and metoclopramide was given orally thereafter for 4 days. The patients
      were then crossed over to receive the other antiemetic regimen in their next
      cycle of chemotherapy. Among 43 evaluable patients who received both cycles of
      treatment, success in controls of nausea and emesis were not significantly
      different between the two regimens in both acute and delayed phases.
      Restlessness, as a side effect, occurred more often in metoclopramide arm
      compared to ginger arm (P=0.109). In conclusion, addition of ginger to standard
      antiemetic regimen has no advantage in reducing nausea or vomiting in acute phase
      of cisplatin-induced emesis. In delayed phase, ginger and metoclopramide have no
      statistically significant difference in efficacy.

PMID- 15571612
TI  - Laparoscopic port-site metastases in patients with gynecological malignancies.
AB  - OBJECTIVE: The purpose of this study is to review all reported cases of
      laparoscopic port-site metastases in patients with gynecological malignancies.
      Potential etiologies as well as options for prevention are discussed. METHODS: We
      searched the Medline database for English-language articles presenting raw data
      on laparoscopic port-site metastases in patients with gynecological malignancies.
      RESULTS: We found 31 articles describing port-site metastases in 58 patients.
      Forty patients had low malignant potential (seven patients) or invasive ovarian
      carcinoma (33 patients). The median age of these patients was 50 years (range: 22
      79), and 83% had advanced (stage III or IV) disease. Seventy-one percent of the
      patients (24 of 34) had ascites, and 97% (29 of 30) had carcinomatosis. Seventy
      five percent of the laparoscopic procedures in this group were performed for
      diagnosis. Median time to diagnosis of port-site metastases was 17 days (range: 4
      730). Seventy-one percent of port-site recurrences (15 of 21) were isolated to a
      tissue-manipulating port. Twelve patients had port-site metastases after
      laparoscopy for cervical cancer. The median age was 44 years (range: 31-74).
      Eighty percent of cases were squamous cell carcinoma. In 75% of the patients,
      laparoscopy was performed for therapeutic purposes. The median time to diagnosis
      of port-site metastases was 5 months (range: 1.5-19). Four patients had port-site
      metastases after laparoscopy for uterine cancer. The median age was 63 years
      (range: 56-72). The median time to diagnosis of metastases was 13.5 months
      (range: 6-21). Half of the recurrences were in the tissue-manipulating port. Port
      site metastases after laparoscopy were reported for one patient each with a
      diagnosis of fallopian tube carcinoma and vaginal carcinoma. CONCLUSIONS:
      Laparoscopic port-site metastases are a potential complication of laparoscopy in
      patients with gynecological malignancies, even in patients with early-stage
      disease.

PMID- 15571613
TI  - HER-2 and cancer antigen 125 evaluation in ovarian borderline tumors by
      immunohistochemistry and fluorescence in situ hybridization.
AB  - The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45
      borderline ovarian tumors (BOTs) and investigated the correlation of these
      biologic markers with histologic type, clinical stage, and outcome. The level of
      CA 125 protein was assessed using DAKO's M-11 clone antibody in
      immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression
      was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy
      number per cell was investigated through fluorescence in situ hybridization
      (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression
      of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors)
      and significantly associated with the serous histologic type. However, CA 125
      expression did not associate with clinical stage or outcome. Protein
      overexpression or gene amplification of HER-2 was not found. However, abnormal
      FISH results were detected in 16% (seven out of 45 patients) of specimens
      comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal
      FISH results were found to be independent of CA 125 expression and histologic
      type whereas they positively associate with advanced clinical stage. Our data
      show that HER-2 is not altered in BOTs, and the presence of aneusomy for
      chromosome 17 and HER-2 may predict tumor progression.

PMID- 15571614
TI  - Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and
      epithelial ovarian cancer.
AB  - The objective of the study was to evaluate the prognostic effect of p53, Her-2,
      and EGFR in borderline and epithelial ovarian cancer. Tumor tissue from 85
      patients with borderline and 783 patients with epithelial ovarian cancer stage I
      IV were analyzed immunohistochemically for p53 positivity and over-expression of
      Her-2 and EGFR. In the ovarian cancer (OC) group 415 patients (53%) had p53
      positive tumors, 272 (35%) had tumors with Her-2 over-expression, and 483 (62%)
      had over-expression of EGFR. In the OC group the classical prognostic factors
      (older age, higher FIGO stage, and poorer differentiated stage) had significant
      prognostic value in both uni- and multivariate analyses. Multivariate analyses in
      the OC group proved p53 positivity to increase mortality significantly depending
      on the grade of the tumor. Her-2 likewise increased the risk of mortality
      significantly in this group depending on the grade of the tumor. EGFR on the
      other hand did not have any additional prognostic effect in the OC group after
      adjustment for the classical prognostic and molecular factors was made. In the
      borderline group Her-2 and EGFR over-expression in combination, adjusted for age
      and p53, significantly improved the prognosis.

PMID- 15571615
TI  - A pilot study for a screening trial of cervical fluorescence spectroscopy.
AB  - Fluorescence spectroscopy is a promising technology for detection of epithelial
      precancers and cancers. In preparation for a multicenter phase II screening
      trial, a pilot trial was conducted to test data collection and patient
      examination procedures, use data forms, time procedures, and identify problems
      with preliminary data analysis. Women 18 years of age and older underwent a
      questionnaire, a complete history, and a physical examination, including a pan
      colposcopy of the lower genital tract. A fiber-optic probe measured fluorescence
      excitation-emission matrices at 1-3 cervical sites for 58 women. The data
      collection procedures, data forms, and procedure times worked well, although
      collection times for all the clinical data take an average of 28 min. The
      clinical team followed procedures well, and the data could be retrieved from the
      database at all sites. The multivariate analysis algorithm correctly identified
      squamous normal tissue 99% of the time and columnar normal tissue only 7%. The
      assessment of ploidy from monolayer samples was not accurate in this small
      sample. The study was successful as a pilot trial. We learned who participated,
      who withdrew, how often abnormalities were present, and that algorithms that have
      worked extremely well in previous studies do not work as well when a few study
      parameters are changed. The current algorithm for diagnosis identified squamous
      normal tissue very accurately and did less well for columnar normal tissue.
      Inflammation may be an explanation for this phenomenon. Fluorescence spectroscopy
      is a promising technology for the detection of epithelial precancers and cancers.
      The screening trial of fluorescence and reflectance spectroscopy was successful.

PMID- 15571616
TI  - The large loop excision of the transformation zone cut or blend thermal artefact
      study: a randomized controlled trial.
AB  - The objective of this randomized controlled trial was to determine whether the
      pure cut setting results in less thermal artefact than the traditional blend
      setting when performing a large loop excision of the transformation zone (LLETZ).
      Forty-nine consenting women were randomized to undergo an LLETZ procedure using
      either the pure cut or the blend setting. Two histopathologists, who were blind
      to the randomization, examined the specimens and then graded and measured the
      degree of thermal artefact. No significant difference was noted at the epithelial
      margin. At the deep stromal margins, in the blend group, the mean thickness of
      thermal artefact was 0.382 mm (95% CI, 0.350-0.414) and in the cut group 0.325 mm
      (95% CI, 0.297-0.353). This was statistically significant. No significant
      difference was detected in terms of grading of thermal artefact, the presence of
      dysplasia at the specimen margins, or in positive follow-up smears. Although
      there was less thermal artefact at the deep stromal margin, cautery at this
      margin does not generally interfere with pathological assessment of the specimen
      and the pure cut setting does not produce a clinically significant decrease in
      the degree of thermal artefact.

PMID- 15571617
TI  - Adjuvant chemotherapy with cisplatin, ifosfamide, and doxorubicin followed by
      radiotherapy in localized uterine sarcomas: results of a case-control study with
      radiotherapy alone.
AB  - Uterine sarcoma is a poor prognosis disease, with a high risk of metastatic
      relapse. We conducted a study of adjuvant chemotherapy with cisplatin,
      ifosfamide, and doxorubicin followed by radiotherapy (n=18). The results were
      then compared in a matched case-controlled study to radiotherapy alone (n=16) or
      no therapy at all (n=2). Chemotherapy consisted in three cycles of adriamyein
      platinum-ifosfamide (API) (doxorubicin 60 mg /m2 on day 1; cisplatin 100 mg /m2
      on day 2; ifosfamide 5 g /m2 on day 1+mesna 5 g /m2 on day 1+granulocyte colony
      stimulating factor; q 3 weeks). Drug doses were reduced (20% for ifosfamide and
      cisplatin) four times (four patients) due to hematologic toxicity. Compared to a
      case-control study of adjuvant radiotherapy alone, results were not decreased by
      the addition of a toxic chemotherapy. CONCLUSION: Adjuvant API chemotherapy
      followed by radiotherapy is a feasible protocol; a multicenter phase III study
      comparing radiotherapy alone versus API chemotherapy followed by radiotherapy
      just began in France.

PMID- 15571618
TI  - Immunohistochemical expression of CD10 antigen in uterine adenosarcoma.
AB  - Uterine adenosarcoma (UAS) is microscopically characterized by a biphasic growth
      pattern. By definition, the epithelial component is benign, whereas the stromal
      component typically has the appearance of a low-grade sarcoma, usually an
      endometrial stromal sarcoma. CD10 acts by reducing cellular response to peptide
      hormones and is currently regarded as a specific marker for endometrial stromal
      tumors. In this international multicenter study, we further explored CD10
      immunoreactivity in 30 UASs. We encountered CD10 positivity of the sarcomatous
      component in 18/20 (90%) of UASs, in five of eight (63%) of UASs with sarcomatous
      overgrowth as well as in both cases of recurrent UAS. The epithelial component
      stained negative in all cases. These findings suggest that CD10 can be used to
      differentiate UAS from cellular leiomyoma, or in case endometrial stromal cells
      exhibit muscle differentiation. Furthermore, CD10 positivity in recurrent UAS
      might guide the pathologist toward an endometrial stromal origin.

PMID- 15571619
TI  - Omentopexy for reconstruction of the perineum following a radical vulvectomy: a
      case report.
AB  - Colorectal surgeons have used omentum based on the left gastric epiploic vessels
      after any major operation in the pelvis(1). Omental flaps reach very well into
      the pelvis by the retrocolic route and have been used in the past for better and
      quicker healing of perineal defects following abdominoperineal resections(2,3).
      Omentum has excellent healing properties, which can be, used even as free
      flaps(4).

PMID- 15571621
TI  - A simulation model of Escherichia coli osmoregulatory switch using E-CELL system.
AB  - BACKGROUND: Bacterial signal transduction mechanism referred to as a "two
      component regulatory systems" contributes to the overall adaptability of the
      bacteria by regulating the gene expression. Osmoregulation is one of the well
      studied two component regulatory systems comprising of the sensor, EnvZ and the
      cognate response regulator, OmpR, which together control the expression of OmpC
      and OmpF porins in response to the osmolyte concentration. RESULTS: A
      quantitative model of the osmoregulatory switch operative in Escherichia coli was
      constructed by integrating the enzyme rate equations using E-CELL system. Using
      the substance reactor logic of the E-CELL system, a total of 28 reactions were
      defined from the injection of osmolyte till the regulated expression of porins by
      employing the experimental kinetic constants as reported in literature. In the
      case of low osmolarity, steady state production of OmpF and repression of OmpC
      was significant. In this model we show that the steady state - production of OmpF
      is dramatically reduced in the high osmolarity medium. The rate of OmpC
      production increased after sucrose addition, which is comparable with literature
      results. The relative porin production seems to be unaltered with changes in cell
      volume changes, ATP, EnvZ and OmpR at low and high osmolarity conditions. But the
      reach of saturation was rapid at high and low osmolarity with altered levels of
      the above components. CONCLUSIONS: The E-CELL system allows us to perform virtual
      experiments on the bacterial osmoregulation model. This model does not take into
      account interaction with other networks in the cell. It suggests that the
      regulation of OmpF and OmpC is a direct consequence of the level of OmpRP in the
      cell and is dependent on the way in which OmpRP interacts with ompF and ompC
      regulatory regions. The preliminary simulation experiment indicates that both
      reaching steady state expression and saturation is delayed in the case of OmpC
      compared to OmpF. Experimental analysis will help improve the model. The model
      captures the basic features of the generally accepted view of EnvZ-OmpR signaling
      and is a reasonable starting point for building sophisticated models and
      explaining quantitative features of the system.

PMID- 15571622
TI  - The family as a determinant of stunting in children living in conditions of
      extreme poverty: a case-control study.
AB  - BACKGROUND: Malnutrition in children can be a consequence of unfavourable
      socioeconomic conditions. However, some families maintain adequate nutritional
      status in their children despite living in poverty. The aim of this study was to
      ascertain whether family-related factors are determinants of stunting in young
      Mexican children living in extreme poverty, and whether these factors differ
      between rural or urban contexts. METHODS: A case-control study was conducted in
      one rural and one urban extreme poverty level areas in Mexico. Cases comprised
      stunted children aged between 6 and 23 months. Controls were well-nourished
      children. Independent variables were defined in five dimensions: family
      characteristics; family income; household allocation of resources and family
      organisation; social networks; and child health care. Information was collected
      from 108 cases and 139 controls in the rural area and from 198 cases and 211
      controls in the urban area. Statistical analysis was carried out separately for
      each area; unconditional multiple logistic regression analyses were performed to
      obtain the best explanatory model for stunting. RESULTS: In the rural area, a
      greater risk of stunting was associated with father's occupation as farmer and
      the presence of family networks for child care. The greatest protective effect
      was found in children cared for exclusively by their mothers. In the urban area,
      risk factors for stunting were father with unstable job, presence of small social
      networks, low rate of attendance to the Well Child Program activities, breast
      feeding longer than six months, and two variables within the family
      characteristics dimension (longer duration of parents' union and migration from
      rural to urban area). CONCLUSIONS: This study suggests the influence of the
      family on the nutritional status of children under two years of age living in
      extreme poverty areas. Factors associated with stunting were different in rural
      and urban communities.Therefore, developing and implementing health programs to
      tackle malnutrition should take into account such differences that are
      consequence of the social, economic, and cultural contexts in which the family
      lives.

PMID- 15571623
TI  - Homozygosity for a missense mutation in the 67 kDa isoform of glutamate
      decarboxylase in a family with autosomal recessive spastic cerebral palsy:
      parallels with Stiff-Person Syndrome and other movement disorders.
AB  - BACKGROUND: Cerebral palsy (CP) is an heterogeneous group of neurological
      disorders of movement and/or posture, with an estimated incidence of 1 in 1000
      live births. Non-progressive forms of symmetrical, spastic CP have been
      identified, which show a Mendelian autosomal recessive pattern of inheritance. We
      recently described the mapping of a recessive spastic CP locus to a 5 cM
      chromosomal region located at 2q24-31.1, in rare consanguineous families.
      METHODS: Here we present data that refine this locus to a 0.5 cM region, flanked
      by the microsatellite markers D2S2345 and D2S326. The minimal region contains the
      candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67),
      involved in conversion of the amino acid and excitatory neurotransmitter
      glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
      RESULTS: A novel amino acid mis-sense mutation in GAD67 was detected, which
      segregated with CP in affected individuals. CONCLUSIONS: This result is
      interesting because auto-antibodies to GAD67 and the more widely studied GAD65
      homologue encoded by the GAD2 gene, are described in patients with Stiff-Person
      Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further
      investigation seems merited of the possibility that variation in the GAD1
      sequence, potentially affecting glutamate/GABA ratios, may underlie this form of
      spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised
      excitotoxicity of glutamate in various contexts.

PMID- 15571624
TI  - Ectopic paraesophageal mediastinal parathyroid adenoma, a rare cause of acute
      pancreatitis.
AB  - BACKGROUND: The manifestation of primary hyperparathyroidism with acute
      pancreatitis is a rare event. Ectopic paraesophageal parathyroid adenomas account
      for about 5%-10% of primary hyperparathyroidism and surgical resection results in
      cure of the disease. CASE PRESENTATION: A 71-year-old woman was presented with
      acute pancreatitis and hypercalcaemia. During the investigation of hypercalcemia,
      a paraesophageal ectopic parathyroid mass was detected by computerized tomography
      (CT) scan and 99mTc sestamibi scintigraphy. The tumor was resected via a cervical
      collar incision and calcium and parathormone tumor levels returned to normal
      within 48 hours. CONCLUSIONS: Acute pancreatitis associated with hypercalcaemia
      should pose the suspicion of primary hyperparathyroidism. Accurate preoperative
      localization of an ectopic parathyroid adenoma, by using the combination of 99mTc
      sestamibi scintigraphy and CT scan of the neck and chest allows successful
      surgical treatment.

PMID- 15571625
TI  - Tumor taxonomy for the developmental lineage classification of neoplasms.
AB  - BACKGROUND: The new "Developmental lineage classification of neoplasms" was
      described in a prior publication. The classification is simple (the entire
      hierarchy is described with just 39 classifiers), comprehensive (providing a
      place for every tumor of man), and consistent with recent attempts to
      characterize tumors by cytogenetic and molecular features. A taxonomy is a list
      of the instances that populate a classification. The taxonomy of neoplasia
      attempts to list every known term for every known tumor of man. METHODS: The
      taxonomy provides each concept with a unique code and groups synonymous terms
      under the same concept. A Perl script validated successive drafts of the taxonomy
      ensuring that: 1) each term occurs only once in the taxonomy; 2) each term occurs
      in only one tumor class; 3) each concept code occurs in one and only one
      hierarchical position in the classification; and 4) the file containing the
      classification and taxonomy is a well-formed XML (eXtensible Markup Language)
      document. RESULTS: The taxonomy currently contains 122,632 different terms
      encompassing 5,376 neoplasm concepts. Each concept has, on average, 23 synonyms.
      The taxonomy populates "The developmental lineage classification of neoplasms,"
      and is available as an XML file, currently 9+ Megabytes in length. A
      representation of the classification/taxonomy listing each term followed by its
      code, followed by its full ancestry, is available as a flat-file, 19+ Megabytes
      in length. The taxonomy is the largest nomenclature of neoplasms, with more than
      twice the number of neoplasm names found in other medical nomenclatures,
      including the 2004 version of the Unified Medical Language System, the
      Systematized Nomenclature of Medicine Clinical Terminology, the National Cancer
      Institute's Thesaurus, and the International Classification of Diseases
      Oncolology version. CONCLUSIONS: This manuscript describes a comprehensive
      taxonomy of neoplasia that collects synonymous terms under a unique code number
      and assigns each tumor to a single class within the tumor hierarchy. The entire
      classification and taxonomy are available as open access files (in XML and flat
      file formats) with this article.

PMID- 15571626
TI  - Dissemination of information to General Practitioners: a questionnaire survey.
AB  - BACKGROUND: Early identification of permanent hearing impairment in children
      enables appropriate intervention which reduces adverse developmental outcomes.
      The UK Government has introduced a universal hearing screening programme for
      neonates. All involved health professionals, including those in Primary Care,
      need to be aware of the service to enable them to offer appropriate support to
      their patients. A programme of information dissemination within Primary Care was
      therefore undertaken. The aim of the current study was to determine the extent to
      which the information had reached General Practitioners (GPs), the GPs' preferred
      mode of dissemination and the sources from which GPs accessed information
      METHODS: Postal questionnaire survey of a randomised sample of 1000 GPs in the
      Phase I pilot sites of the Neonatal Hearing Screening Programme (NHSP). RESULTS:
      Responses were received from 54.2% of the sample. Just under 50% of those
      responding had received information, 62.2% of respondents said they would like to
      receive more information and the preferred methods of dissemination were the
      written word and web-sites to allow access when needed. Few GPs perceive
      themselves to have a core role in the delivery of the NHSP and thence a need for
      knowledge in the subject. Many are keen to delegate detail to a third party,
      usually the health visitor, who has traditionally had responsibility for hearing
      screening. CONCLUSIONS: Dissemination efforts for service developments of
      relevance to GPs should concentrate on advertising a website address via brief
      but memorable posted literature and/or articles in relevant journals and
      magazines. The website should be GP-friendly, and have a dedicated area for GPs
      including information of specific relevance and downloadable information sheets.

PMID- 15571627
TI  - Gene expression profiling reveals novel TGFbeta targets in adult lung
      fibroblasts.
AB  - BACKGROUND: Transforming growth factor beta (TGFbeta), a multifunctional
      cytokine, plays a crucial role in the accumulation of extracellular matrix
      components in lung fibrosis, where lung fibroblasts are considered to play a
      major role. Even though the effects of TGFbeta on the gene expression of several
      proteins have been investigated in several lung fibroblast cell lines, the global
      pattern of response to this cytokine in adult lung fibroblasts is still unknown.
      METHODS: We used Affymetrix oligonucleotide microarrays U95v2, containing
      approximately 12,000 human genes, to study the transcriptional profile in
      response to a four hour treatment with TGFbeta in control lung fibroblasts and in
      fibroblasts from patients with idiopathic and scleroderma-associated pulmonary
      fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5)
      and of analysis of variance models was used to identify TGFbeta-regulated genes.
      Additional criteria were an average up- or down- regulation of at least two fold.
      RESULTS: Exposure of fibroblasts to TGFbeta had a profound impact on gene
      expression, resulting in regulation of 129 transcripts. We focused on genes not
      previously found to be regulated by TGFbeta in lung fibroblasts or other cell
      types, including nuclear co-repressor 2, SMAD specific E3 ubiquitin protein
      ligase 2 (SMURF2), bone morphogenetic protein 4, and angiotensin II receptor type
      1 (AGTR1), and confirmed the microarray results by real time-PCR. Western
      Blotting confirmed induction at the protein level of AGTR1, the most highly
      induced gene in both control and fibrotic lung fibroblasts among genes encoding
      for signal transduction molecules. Upregulation of AGTR1 occurred through the
      MKK1/MKK2 signalling pathway. Immunohistochemical staining showed AGTR1
      expression by lung fibroblasts in fibroblastic foci within biopsies of idiopathic
      pulmonary fibrosis. CONCLUSIONS: This study identifies several novel TGFbeta
      targets in lung fibroblasts, and confirms with independent methods the induction
      of angiotensin II receptor type 1, underlining a potential role for angiotensin
      II receptor 1 antagonism in the treatment of lung fibrosis.

PMID- 15571628
TI  - DNA-free RNA preparations from mycobacteria.
AB  - BACKGROUND: To understand mycobacterial pathogenesis analysis of gene expression
      by quantification of RNA levels becomes increasingly important. However, current
      preparation methods yield mycobacterial RNA that is contaminated with chromosomal
      DNA. RESULTS: After sonication of RNA samples from Mycobacterium smegmatis
      genomic DNA is efficiently removed by DNaseI in contrast to untreated samples.
      CONCLUSIONS: This procedure eliminates one of the most prevalent error sources in
      quantification of RNA levels in mycobacteria.

PMID- 15571629
TI  - The apolipoprotein E polymorphism and the cholesterol-raising effect of coffee.
AB  - BACKGROUND: The response of serum cholesterol to diet may be affected by the
      apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 polymorphism, which also is a
      significant predictor of variation in the risk of coronary heart disease (CHD)
      and CHD death. Here, we test the hypothesis that the APOE polymorphism may
      modulate the cholesterol-raising effect of coffee. OBJECTIVE: We determined the
      effect of a coffee abstention period and a daily intake of 600 mL coffee on serum
      cholesterol and triglycerides with respect to the APOE polymorphism. DESIGN: 121
      healthy, non-smoking men (22%) and women (78%) aged 29-65 years, took part in a
      study with four intervention periods: 1 and 3) a coffee free period of three
      weeks, 2 and 4) 600 mL coffee/day for four weeks. RESULTS: APOE epsilon2 positive
      individuals had significantly lower total cholesterol concentration at baseline
      (4.68 mmol/L and 5.28 mmol/L, respectively, p = 0.01), but the cholesterol
      raising effect of coffee was not influenced significantly by APOE allele carrier
      status. CONCLUSIONS: The APOE epsilon 2 allele is associated with lower serum
      cholesterol concentration. However, the APOE polymorphism does not seem to
      influence the cholesterol-raising effect of coffee.

PMID- 15571630
TI  - Characterisation of weak magnetic field effects in an aqueous glutamic acid
      solution by nonlinear dielectric spectroscopy and voltammetry.
AB  - BACKGROUND: Previous reports indicate altered metabolism and enzyme kinetics for
      various organisms, as well as changes of neuronal functions and behaviour of
      higher animals, when they were exposed to specific combinations of weak static
      and alternating low frequency electromagnetic fields. Field strengths and
      frequencies, as well as properties of involved ions were related by a linear
      equation, known as the formula of ion cyclotron resonance (ICR, abbreviation
      mentioned first by Liboff). Under certain conditions already a aqueous solution
      of the amino acid and neurotransmitter glutamate shows this effect. METHODS: An
      aqueous solution of glutamate was exposed to a combination of a static magnetic
      field of 40 muT and a sinusoidal electromagnetic magnetic field (EMF) with
      variable frequency (2-7 Hz) and an amplitude of 50 nT. The electric conductivity
      and dielectric properties of the solution were investigated by voltammetric
      techniques in combination with non linear dielectric spectroscopy (NLDS), which
      allow the examination of the dielectric properties of macromolecules and
      molecular aggregates in water. The experiments target to elucidate the biological
      relevance of the observed EMF effect on molecular level. RESULTS: An ion
      cyclotron resonance (ICR) effect of glutamate previously reported by the Fesenko
      laboratory 1998 could be confirmed. Frequency resolution of the sample currents
      was possible by NLDS techniques. The spectrum peaks when the conditions for ion
      cyclotron resonance (ICR) of glutamate are matched. Furthermore, the NLDS spectra
      are different under ICR- and non-ICR conditions: NLDS measurements with rising
      control voltages from 100-1100 mV show different courses of the intensities of
      the low order harmonics, which could possibly indicate "intensity windows".
      Furthermore, the observed magnetic field effects are pH dependent with a narrow
      optimum around pH 2.85. CONCLUSIONS: Data will be discussed in the context with
      recent published models for the interaction of weak EMF with biological matter
      including ICR. A medical and health relevant aspect of such sensitive effects
      might be given insofar, because electromagnetic conditions for it occur at many
      occasions in our electromagnetic all day environment, concerning ion involvement
      of different biochemical pathways.

PMID- 15571631
TI  - Host resistance does not explain variation in incidence of male-killing bacteria
      in Drosophila bifasciata.
AB  - BACKGROUND: Selfish genetic elements that distort the sex ratio are found widely.
      Notwithstanding the number of records of sex ratio distorters, their incidence is
      poorly understood. Two factors can prevent a sex ratio distorter from invading:
      inability of the sex ratio distorter to function (failure of mechanism or
      transmission), and lack of drive if they do function (inappropriate ecology for
      invasion). There has been no test to date on factors causing variation in the
      incidence of sex ratio distorting cytoplasmic bacteria. We therefore examined
      whether absence of the male-killing Wolbachia infection in D. bifasciata in
      Hokkaido island of Japan, in contrast to the presence of infection on the
      proximal island of Honshu, was associated with failure of the infection to
      function properly on the Hokkaido genetic background. RESULTS: The male-killer
      both transmitted and functioned well following introgression to each of 24
      independent isofemale inbred lines carrying Hokkaido genetic backgrounds. This
      was maintained even under stringent conditions of temperature. We therefore
      reject the hypothesis that absence of infection is due to its inability to kill
      males and transmit on the Hokkaido genetic background. Further trap data
      indicates that D. bifasciata may occur at different densities in Hokkaido and
      Honshu populations, giving some credence to the idea that ecological
      differentiation could be important. CONCLUSIONS: The absence of the infection
      from the Hokkaido population is not caused by failure of the male-killer to
      function on the Hokkaido genetic background.

PMID- 15571632
TI  - prot4EST: translating expressed sequence tags from neglected genomes.
AB  - BACKGROUND: The genomes of an increasing number of species are being investigated
      through generation of expressed sequence tags (ESTs). However, ESTs are prone to
      sequencing errors and typically define incomplete transcripts, making downstream
      annotation difficult. Annotation would be greatly improved with robust
      polypeptide translations. Many current solutions for EST translation require a
      large number of full-length gene sequences for training purposes, a resource that
      is not available for the majority of EST projects. RESULTS: As part of our
      ongoing EST programs investigating these "neglected" genomes, we have developed a
      polypeptide prediction pipeline, prot4EST. It incorporates freely available
      software to produce final translations that are more accurate than those derived
      from any single method. We show that this integrated approach goes a long way to
      overcoming the deficit in training data. CONCLUSIONS: prot4EST provides a
      portable EST translation solution and can be usefully applied to >95% of EST
      projects to improve downstream annotation. It is freely available from
      http://www.nematodes.org/PartiGene.

PMID- 15571633
TI  - Comparison of nested PCR and real time PCR of Herpesvirus infections of central
      nervous system in HIV patients.
AB  - BACKGROUND: Molecular detection of herpesviruses DNA is considered as the
      reference standard assay for diagnosis of central nervous system infections. In
      this study nested PCR and real time PCR techniques for detection of Herpes
      simplex virus type 1 (HSV-1), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
      in cerebrospinal fluid of HIV patients were compared. METHODS: Forty-six, 85 and
      145 samples previously resulted positive for HSV-1, CMV and EBV by nested PCR and
      150 randomly chosen negative samples among 1181 collected in the period 1996-2003
      were retrospectively reassessed in duplicate by real time PCR and nested PCR.
      RESULTS: Samples giving positive results for CMV, HSV-1 and EBV with nested PCR
      were positive also with real time PCR. One of the negative samples resulted
      positive for HSV and one for EBV. Real time PCR showed comparable sensitivity and
      specificity vs nested PCR. CONCLUSION: Real time PCR proved to be a suitable
      method for diagnosis of herpesvirus infections in CNS, showing comparable
      sensitivity and being less time consuming than nested PCR.

PMID- 15571634
TI  - Constraint Logic Programming approach to protein structure prediction.
AB  - BACKGROUND: The protein structure prediction problem is one of the most
      challenging problems in biological sciences. Many approaches have been proposed
      using database information and/or simplified protein models. The protein
      structure prediction problem can be cast in the form of an optimization problem.
      Notwithstanding its importance, the problem has very seldom been tackled by
      Constraint Logic Programming, a declarative programming paradigm suitable for
      solving combinatorial optimization problems. RESULTS: Constraint Logic
      Programming techniques have been applied to the protein structure prediction
      problem on the face-centered cube lattice model. Molecular dynamics techniques,
      endowed with the notion of constraint, have been also exploited. Even using a
      very simplified model, Constraint Logic Programming on the face-centered cube
      lattice model allowed us to obtain acceptable results for a few small proteins.
      As a test implementation their (known) secondary structure and the presence of
      disulfide bridges are used as constraints. Simplified structures obtained in this
      way have been converted to all atom models with plausible structure. Results have
      been compared with a similar approach using a well-established technique as
      molecular dynamics. CONCLUSIONS: The results obtained on small proteins show that
      Constraint Logic Programming techniques can be employed for studying protein
      simplified models, which can be converted into realistic all atom models. The
      advantage of Constraint Logic Programming over other, much more explored,
      methodologies, resides in the rapid software prototyping, in the easy way of
      encoding heuristics, and in exploiting all the advances made in this research
      area, e.g. in constraint propagation and its use for pruning the huge search
      space.

PMID- 15571635
TI  - Mineral water intake reduces blood pressure among subjects with low urinary
      magnesium and calcium levels.
AB  - BACKGROUND: Several previous epidemiological studies have shown a relation
      between drinking water quality and death in cardiovascular disease whereas others
      have not found such a relationship. An intervention study was undertaken to
      evaluate the effect of water with added magnesium and natural mineral water on
      blood pressure. METHODS: A group of 70 subjects with borderline hypertension was
      recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or
      3) natural mineral water, in a random, double blind fashion during four weeks.
      RESULTS: Among persons with an initial low excretion of magnesium or calcium in
      the urine, the urinary excretion of magnesium was increased in the groups
      consuming the two waters containing magnesium after 4 weeks. A significant
      decrease in blood pressure was found in the group consuming mineral water at 2
      and 4 weeks. CONCLUSION: The results suggest that minerals taken in water are
      significant for the body burden and that an intake of mineral water among persons
      with a low urinary excretion of magnesium or calcium may decrease the blood
      pressure. Further studies should investigate the extent of mineral deficiency in
      different populations and the efficiency of different vehicles for supplying
      minerals, particularly magnesium and calcium.

PMID- 15571636
TI  - Disclosure of cancer diagnosis and prognosis: a survey of the general public's
      attitudes toward doctors and family holding discretionary powers.
AB  - BACKGROUND: This study aimed to ask a sample of the general population about
      their preferences regarding doctors holding discretionary powers in relation to
      disclosing cancer diagnosis and prognosis. METHODS: The researchers mailed 443
      questionnaires to registered voters in a ward of Tokyo which had a socio
      demographic profile similar to greater Tokyo's average and received 246 responses
      (response rate 55.5%). We describe and analysed respondents' attitudes toward
      doctors and family members holding discretionary powers in relation to cancer
      diagnoses disclose. RESULTS: Amongst respondents who wanted full disclosure about
      the diagnosis without delay, 117 (69.6 %) respondents agreed to follow the
      doctor's discretion, whilst 111 (66.1 %) respondents agreed to follow the family
      member's decision. For respondents who preferred to have the diagnosis and
      prognosis withheld, 59 (26.5 %) agreed to follow the doctor's decision, and 79
      (35.3 %) of respondents agreed with following family member's wishes.
      CONCLUSIONS: The greater proportion of respondents wants or permits disclosure of
      cancer diagnosis and prognosis. In patients who reveal negative attitudes toward
      being given a cancer disclosure directly, alternative options exist such as
      telling the family ahead of the patient or having a discussion of the cancer
      diagnosis with the patient together with the family. It is recommended that
      health professionals become more aware about the need to provide patients with
      their cancer diagnosis and prognosis in a variety of ways.

PMID- 15571637
TI  - The need for a large-scale trial of fibrate therapy in diabetes: the rationale
      and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
      study. [ISRCTN64783481].
AB  - BACKGROUND: Fibrates correct the typical lipid abnormalities of type 2 diabetes
      mellitus, yet no study, to date, has specifically set out to evaluate the role of
      fibrate therapy in preventing cardiovascular events in this setting. METHODS:
      Subjects with type 2 diabetes, aged 50-75 years, were screened for eligibility to
      participate in a long-term trial of comicronized fenofibrate 200 mg daily
      compared with matching placebo to assess benefits of treatment on the occurrence
      of coronary and other vascular events. People with total cholesterol levels 3.0
      6.5 mmol/L plus either a total-to-HDLc ratio > 4.0 or triglyceride level > 1.0
      mmol/L with no clear indication for lipid-modifying therapy were eligible.
      RESULTS: A total of 9795 people were randomized into the Fenofibrate Intervention
      and Event Lowering in Diabetes (FIELD) trial. All received dietary advice,
      followed by a 6-week single-blind placebo run-in, then a 6-week active run-in
      period before randomization. Participants are being followed up every 6 months
      for outcome events and safety assessments. The study is designed to yield at
      least 500 coronary events (primary endpoint: first nonfatal myocardial infarction
      or coronary death) over 5 years, to have 80% power to identify as statistically
      significant at 2P = 0.05 a 22% reduction in such events, using intention-to-treat
      methods. CONCLUSIONS: Type 2 diabetes is the most common endocrine disorder
      worldwide, and its prevalence is increasing. The current evidence about use of
      fibrates in type 2 diabetes, from around 2000 people treated, will increase with
      FIELD to evidence from around 12000. FIELD will establish the role of fenofibrate
      treatment in reducing cardiovascular risk in people with type 2 diabetes. The
      main results are expected to be available in late 2005.

PMID- 15571638
TI  - Is the stethoscope on the verge of becoming obsolete?

PMID- 15571639
TI  - Automated lung sound analysis in patients with pneumonia.
AB  - OBJECTIVE: To determine whether objectively detected lung sounds were
      significantly different in patients with pneumonia than those in asymptomatic
      subjects, and to quantify the pneumonia findings for teaching purposes. METHODS:
      At a community teaching hospital we used a multi-channel lung sound analyzer to
      examine a learning sample of 50 patients diagnosed with pneumonia and 50 control
      subjects. Automated quantification and characterization of the lung sounds
      commonly recognized to be associated with pneumonia were used to generate an
      "acoustic pneumonia score." These were examined in the learning sample and then
      prospectively tested in 50 patients and 50 controls. RESULTS: The acoustic
      pneumonia score averaged 13 in the learning sample and 11 in the test sample of
      pneumonia patients. The scores were 2 and 3 in the controls. The positive
      predictive value of a score higher than 6 was 0.94 in the learning sample and
      0.87 in the test sample. The sensitivities in the 2 groups were 0.90 and 0.78,
      and the specificities were 0.94 and 0.88, respectively. Adventitious sounds were
      more common in pneumonia patients (inspiratory crackles 81% vs 28%, expiratory
      crackles 65% vs 9%, rhonchi 19% vs 0%). CONCLUSION: Our lung sound analyzer found
      significant differences between lung sounds in patients with pneumonia and in
      asymptomatic controls. Computerized lung sound analysis can provide objective
      evidence supporting the diagnosis of pneumonia. We believe that the lung-sound
      data produced by our device will help to teach physical diagnosis.

PMID- 15571640
TI  - Comparison of different exercise tests in assessing outcomes of pulmonary
      rehabilitation.
AB  - INTRODUCTION: Common modalities of clinical exercise testing for outcome
      measurement after pulmonary rehabilitation (PR) include walk tests, progressive
      cycle ergometry, and cycle endurance testing. We hypothesized that patients'
      responses to PR, as measured by those 3 tests, are differentially correlated, and
      we designed a study to investigate the tests' capacity to detect changes after
      PR. METHODS: We prospectively tested 37 male patients with stable chronic
      obstructive pulmonary disease who completed a comprehensive 6-week PR program
      that included supervised exercise training that emphasized steady-state lower
      limb aerobic exercise. Before and after the PR program the patients underwent 6
      minute walk test, progressive cycle ergometry, and cycle endurance testing (at
      80% of the peak work rate achieved during progressive cycle ergometry). The
      exercise performance indices of interest were the peak oxygen uptake (VO2max) and
      maximum work-rate (Wmax) during progressive cycle ergometry, the cycling
      endurance time, and the 6-minute walk distance (6MWD). RESULTS: After PR there
      were statistically significant improvements in 6MWD (16%, p <0.001), VO2max (53%,
      p=0.004), Wmax (30%, p=0.001), and cycling endurance time (144%, p <0.001). The
      changes in VO2max and Wmax were significantly correlated (r=0.362, p=0.027), as
      were the changes in endurance time and Wmax (r=0.406, p=0.013). There was no
      significant correlation between changes in any other exercise index. CONCLUSIONS:
      Among the frequently used exercise tests in PR, the most responsive index is the
      endurance time. The correlation between the post-PR changes in the various
      exercise indices is poor.

PMID- 15571641
TI  - Nebulizer use and maintenance by cystic fibrosis patients: a survey study.
AB  - INTRODUCTION: Patients with cystic fibrosis (CF) suffer from chronic infection of
      the airways, and typical CF therapies include aerosolized medications. There is
      recent evidence that home nebulizers become contaminated by bacteria, causing
      concern that nebulizers may be a source of bacterial infection of the lower
      airways. A recent consensus document on infection-control issues for the CF
      population included recommendations on cleaning and disinfecting nebulizers.
      METHODS: We surveyed 39 patients and their parents, as well as 54 respiratory
      therapists, regarding their routine nebulizer use and maintenance practices.
      RESULTS: All the patients used at least one nebulized medication, and they used a
      variety of nebulizers, obtained from a wide variety of sources. Thirty percent of
      the patients used nebulizers well beyond the manufacturer's recommended
      replacement date. Ninety percent of the patients rinsed their nebulizers
      following use, but only 15% performed any routine disinfection. The respiratory
      therapists' nebulizer cleaning methods were widely disparate, with only 70%
      performing some method of rinsing. The respiratory therapists' self-report of
      cleaning methods and their instructions to patients regarding frequency of
      cleaning were so diverse that no standard is evident. CONCLUSION: This study
      demonstrates that CF patients and their respiratory therapists should immediately
      address and improve their nebulizer cleaning methods and replacement practices.
      There should be more focus on teaching patients to regularly clean and replace
      nebulizers.

PMID- 15571642
TI  - Evaluation of 16 adult disposable manual resuscitators.
AB  - INTRODUCTION: Disposable manual resuscitators are commonly used to ventilate
      patients during cardiopulmonary resuscitation, suctioning, and intrahospital
      transport, and their clinical performance is critical. METHODS: We bench-tested
      16 adult disposable manual resuscitators from 9 different manufacturers. We
      performed a series of tests and made observations using testing industry
      standards as a guideline. Each resuscitator was tested for fraction of delivered
      oxygen (FDO2), tidal volume delivery, drop test, and patient valve lock-up. We
      also made observations about reservoir style, ease or difficulty of attaching the
      positive end-expiratory pressure valve, size, texture, carbon dioxide detector,
      and if the resuscitator was labeled "latex free." RESULTS: Reservoir style and
      manufacturer design significantly affected FDO2. In general, the resuscitators
      with reservoir bags provided better FDO2 than did the resuscitators with tubing
      reservoirs (large-bore or small-bore). Delivered tidal volumes were acceptable
      for all the resuscitators tested. All the resuscitators passed a standard drop
      test. None of the resuscitators had a patient valve lock up at high flow. With
      all but one resuscitator, attaching the positive end-expiratory pressure valve
      was easy and the valve attached securely. Most resuscitators were average in size
      and had good texture, but some were large, somewhat slippery, and difficult to
      handle. Only 2 resuscitators came with carbon dioxide detectors already attached.
      All but one of the resuscitators were labeled "latex free," and the one that was
      not was found not to contain latex proteins. CONCLUSIONS: Resuscitator reservoir
      style and manufacturer design significantly affect FDO2. Some resuscitator models
      may not deliver adequate oxygen in certain clinical circumstances. Each
      institution should evaluate and choose the resuscitator that best fits its needs,
      while meeting established performance criteria.

PMID- 15571643
TI  - Fatal acute interstitial pneumonitis complicating polymyositis in a 41-year-old
      man.
AB  - We report a case of a previously healthy 41-year-old man who was admitted for
      progressive dyspnea and cough, which culminated in respiratory failure, shock,
      and death. Lung and muscle biopsy results were consistent with interstitial lung
      disease secondary to polymyositis. Polymyositis and dermatomyositis are rare
      autoimmune diseases that primarily affect the muscles and skin, with frequent
      extramuscular and specifically pulmonary manifestations. Respiratory
      complications are in 2 categories: primary (the interstitial lung diseases, which
      can be acute or chronic) and secondary (aspiration pneumonia/pneumonitis, muscle
      weakness, infection, drug-induced disease, pulmonary congestion secondary to
      heart failure, pulmonary hypertension, and pneumomediastinum). Diagnosis of a
      specific interstitial lung disease relies mainly on high-resolution computed
      tomography of the chest and on tissue diagnosis. Prognosis depends on the
      histopathology findings and the specific form of interstitial lung disease and
      its response to therapy, which consists of high-dose steroids and
      immunomodulating agents. Unfortunately, patients with
      polymyositis/dermatomyositis associated with pulmonary complications have a worse
      prognosis than patients with isolated forms.

PMID- 15571644
TI  - Lung adenocarcinoma presenting with enlarged and multiloculated cystic lesions
      over 2 years.
AB  - We report a case of lung adenocarcinoma in which cystic lesions enlarged and
      multiloculated over 2 years. Histological examination of the resected specimen
      found proliferation of nonmucinous adenocarcinoma cells along the alveolar walls,
      revealing bronchioloalveolar cell carcinoma type extension. In cystic lesions,
      particularly those not associated with inflammation, lung adenocarcinoma,
      particularly bronchioloalveolar cell carcinoma type, should be a diagnostic
      consideration. .

PMID- 15571645
TI  - Pulmonary venous thrombosis and infarction complicating pulmonary venous stenosis
      following radiofrequency ablation.
AB  - Pulmonary vein stenosis is a recently described complication of radiofrequency
      ablation. We report a patient who experienced thrombosis of the lingular vein and
      pulmonary infarction resulting from mild single-vessel pulmonary vein stenosis.
      This report extends available experience with complications of radiofrequency
      ablation, by demonstrating pulmonary venous thrombosis as a complication of
      relatively minor (approximately 50% luminal narrowing) stenosis of a single
      pulmonary vein, despite the fact that the patient was taking an anticoagulant. .

PMID- 15571646
TI  - Community-acquired pneumonia due to Pasteurella multocida.
AB  - Most cases of community-acquired pneumonia result from infection with predictable
      common pathogens. However, rare patients develop pneumonia from unusual bacterial
      species such as Pasteurella multocida, a Gram-negative oral commensal of most
      dogs and cats. The majority of P. multocida infections involve skin and soft
      tissue and complicate a bite or scratch. I report the case of an elderly man who
      owned 16 cats and developed bacteremic pneumonia with P. multocida. .

PMID- 15571647
TI  - Appropriate empiric antimicrobial therapy of nosocomial pneumonia: the role of
      the carbapenems.
AB  - Nosocomial pneumonia is the leading cause of death in patients with hospital
      acquired infections. The development of nosocomial pneumonia prolongs
      hospitalization, which may cause additional days in the intensive care unit,
      thereby increasing overall health care costs. Empiric treatment of nosocomial
      pneumonia with therapies that are subsequently shown to be inappropriate therapy
      (defined as antimicrobial therapy that does not cover the infecting pathogens)
      has a detrimental effect on patient survival and can increase morbidity, length
      of hospital stay, and mortality. Delayed therapy can also have similar
      consequences. Therefore, it is necessary to begin treatment with the most
      appropriate regimen as soon as possible. This review considers the early use of
      appropriate, broad-spectrum empiric antimicrobial therapy for treating patients
      with nosocomial pneumonia and describes where and when the carbapenems are
      particularly useful. The carbapenems are active against both Gram-positive and
      Gram-negative pathogens, including anaerobes; resistance to carbapenems remains
      rare.

PMID- 15571660
TI  - Surfactant solutions and porous substrates: spreading and imbibition.
AB  - In Section 1, spreading of small liquid drops over thin dry porous layers is
      investigated from both theoretical and experimental points of view [V.M. Starov,
      S.R. Kosvintsev, V.D. Sobolev, M.G. Velarde, S.A. Zhdanov, J. Colloid Interface
      Sci. 252 (2002) 397]. Drop motion over a porous layer is caused by an interplay
      of two processes: (a) the spreading of the drop over already saturated parts of
      the porous layer, which results in an expanding of the drop base, and (b) the
      imbibition of the liquid from the drop into the porous substrate, which results
      in a shrinkage of the drop base and an expanding of the wetted region inside the
      porous layer. As a result of these two competing processes, the radius of the
      drop goes through a maximum value over time. A system of two differential
      equations has been derived to describe the evolution with time of radii of both
      the drop base and the wetted region inside the porous layer. This system includes
      two parameters, one accounts for the effective lubrication coefficient of the
      liquid over the wetted porous substrate, and the other is a combination of
      permeability and effective capillary pressure inside the porous layer. Two
      additional experiments were used for an independent determination of these two
      parameters. The system of differential equations does not include any fitting
      parameter after these two parameters are determined. Experiments were carried out
      on the spreading of silicone oil drops over various dry microfiltration membranes
      (permeable in both normal and tangential directions). The time evolution of the
      radii of both the drop base and the wetted region inside the porous layer were
      monitored. All experimental data fell on two universal curves if appropriate
      scales are used with a plot of the dimensionless radii of the drop base and of
      the wetted region inside the porous layer on dimensionless time. The predicted
      theoretical relationships are two universal curves accounting quite satisfactory
      for the experimental data. According to theory predictions [1]: (i) the dynamic
      contact angle dependence on the same dimensionless time as before should be a
      universal function, and (ii) the dynamic contact angle should change rapidly over
      an initial short stage of spreading and should remain a constant value over the
      duration of the rest of the spreading process. The constancy of the contact angle
      on this stage has nothing to do with hysteresis of the contact angle: there is no
      hysteresis in the system under investigation. These conclusions again are in good
      agreement with experimental observations [V.M. Starov, S.R. Kosvintsev, V.D.
      Sobolev, M.G. Velarde, S.A. Zhdanov, J. Colloid Interface Sci. 252 (2002) 397].
      In Section 2, experimental investigations are reviewed on the spreading of small
      drops of aqueous SDS solutions over dry thin porous substrates (nitrocellulose
      membranes) in the case of partial wetting [S. Zhdanov, V. Starov, V. Sobolev, M.
      Velarde, Spreading of aqueous SDS solutions over nitrocellulose membranes. J.
      Colloid Interface Sci. 264 (2003) 481-489]. The time evolution was monitored of
      the radii of both the drop base and the wetted area inside the porous substrate.
      The total duration of the spreading process was subdivided into three stages-the
      first stage: the drop base expands until the maximum value of the drop base is
      reached; the contact angle rapidly decreases during this stage; the second stage:
      the radius of the drop base remains constant and the contact angle decreases
      linearly with time; the third stage: the drop base shrinks and the contact angle
      remains constant. The wetted area inside the porous substrate expends during the
      whole spreading process. Appropriate scales were used with a plot of the
      dimensionless radii of the drop base, of the wetted area inside the porous
      substrate, and the dynamic contact angle on the dimensionless time. Experimental
      data showed [S. Zhdanov, V. Starov, V. Sobolev, M. Velarde, Spreading of aqueous
      SDS solutions over nitrocellulose membranes. J. Colloid Interface Sci. 264 (2003)
      481-489]: the overall time of the spreading of drops of SDS solution over dry
      thin porous substrates decreases with the increase of surfactant concentration;
      the difference between advancing and hydrodynamic receding contact angles
      decreases with the surfactant concentration increase; the constancy of the
      contact angle during the third stage of spreading has nothing to do with the
      hysteresis of contact angle, but determined by the hydrodynamic reasons. It is
      shown using independent spreading experiments of the same drops on nonporous
      nitrocellulose substrate that the static receding contact angle is equal to zero,
      which supports the conclusion on the hydrodynamic nature of the hydrodynamic
      receding contact angle on porous substrates. In Section 3, a theory is developed
      to describe a spontaneous imbibition of surfactant solutions into hydrophobic
      capillaries, which takes into account the micelle disintegration and the
      concentration decreasing close to the moving meniscus as a result of adsorption,
      as well as the surface diffusion of surfactant molecules [N.V. Churaev, G.A.
      Martynov, V.M. Starov, Z.M. Zorin, Colloid Polym. Sci. 259 (1981) 747]. The
      theory predictions are in good agreement with the experimental investigations on
      the spontaneous imbibition of the nonionic aqueous surfactant solution, Syntamide
      5, into hydrophobized quartz capillaries. A theory of the spontaneous capillary
      rise of surfactant solutions in hydrophobic capillaries is presented, which
      connects the experimental observations with the adsorption of surfactant
      molecules in front of the moving meniscus on the bare hydrophobic interface [V.J.
      Starov, Colloid Interface Sci. 270 (2003)]. In Section 4, capillary imbibition of
      aqueous surfactant solutions into dry porous substrates is investigated from both
      theoretical and experimental points of view in the case of partial wetting [V.
      Straov, S. Zhdanov, M. Velarde, J. Colloid Interface Sci. 273 (2004) 589].
      Cylindrical capillaries are used as a model of porous media for theoretical
      treatment of the problem. It is shown that if an averaged pore size of the porous
      medium is below a critical value, then the permeability of the porous medium is
      not influenced by the presence of surfactants at any concentration: the
      imbibition front moves exactly in the same way as in the case of the imbibition
      of the pure water. The critical radius is determined by the adsorption of the
      surfactant molecules on the inner surface of the pores. If an averaged pore size
      is bigger than the critical value, then the permeability increases with
      surfactant concentration. These theoretical conclusions are in agreement with
      experimental observations. In Section 5, the spreading of surfactant solutions
      over hydrophobic surfaces is considered from both theoretical and experimental
      points of view [V.M. Starov, S.R. Kosvintsev, M.G. Velarde, J. Colloid Interface
      Sci. 227 (2000) 185]. Water droplets do not wet a virgin solid hydrophobic
      substrate. It is shown that the transfer of surfactant molecules from the water
      droplet onto the hydrophobic surface changes the wetting characteristics in front
      of the drop on the three-phase contact line. The surfactant molecules increase
      the solid-vapor interfacial tension and hydrophilise the initially hydrophobic
      solid substrate just in front of the spreading drop. This process causes water
      drops to spread over time. The time of evolution of the spreading of a water
      droplet is predicted and compared with experimental observations. The assumption
      that surfactant transfer from the drop surface onto the solid hydrophobic
      substrate controls the rate of spreading is confirmed by experimental
      observations. In Section 6, the process of the spontaneous spreading of a droplet
      of a polar liquid over solid substrate is analyzed in the case when amphiphilic
      molecules (or their amphiphilic fragments) of the substrate surface layer are
      capable of overturning, resulting in a partial hydrophilisation of the surface
      [V.M. Starov, V.M. Rudoy, V.I. Ivanov, Colloid J. (Russian Academy of Sciences
      English Transaction) 61 (3) (1999) 374]. Such a situation may take place, for
      example, during contact of an aqueous droplet with the surface of a polymer whose
      macromolecules have hydrophilic side groups capable of rotating around the
      backbone and during the wetting of polymers containing surface-active additives
      or Langmuir-Blodgett films composed of amphiphilic molecules. It was shown that
      droplet spreading is possible only if the lateral interaction between
      neighbouring amphiphilic molecules (or groups) takes place. This interaction
      results in the tangential transfer of "the overturning state" to some distance in
      front of the advancing three-phase contact line making it partially hydrophilic.
      The quantitative theory describing the kinetics of droplet spreading is developed
      with allowance for this mechanism of self-organization of the surface layer of a
      substrate in the contact with a droplet.

PMID- 15571661
TI  - Manipulating forces between surfaces: applications in colloid science and
      biophysics.
AB  - It is the forces between the microscopic constituents of materials which to a
      large extent determine the macroscopic properties. For example, it is the
      differences in bonding between the carbon atoms which determines the different
      physical properties of carbon and graphite. The same is true in colloidal
      systems. In colloidal systems, there are three common types of long-range
      interactions between particles: van der Waals forces, electrical double layer
      forces and steric forces. In this paper, examples as to how these forces can be
      modified and even manipulated will be given. To convincingly demonstrate these
      effects, it is necessary to measure these interaction forces. We have achieved
      this by using the principles of atomic force microscopy (AFM). The principle is
      simple, a small particle, 5-30 microm, is attached onto a small weak cantilever
      spring. The interaction between this particle and another particle or a surface
      is measured by monitoring the deflection of the spring as the two particles are
      moved together. In this paper, I shall give examples of direct measurements of
      van der Waals, electrical double layer and steric forces and show how they can be
      modified and how these modifications affect the properties of bulk suspensions.
      Similar principles are involved in the interactions of biological materials.
      However, nature is much cleverer than man such that many of the macromolecules on
      cell surfaces are able to specifically recognise only one other molecule. An
      example of this recognition-type interaction, namely, cholera toxin interacting
      with the glycolipid Gm1, will also be presented. Finally, the adhesion of cells
      to surfaces of different surface chemistries has been determined; this is of
      significance in many fields ranging from fouling of filtration membranes on the
      one hand to the biocompatibility of surgical implants on the other.

PMID- 15571662
TI  - Polyelectrolyte multilayer capsules as vehicles with tunable permeability.
AB  - This review is devoted to a novel type of polymer micro- and nanocapsules. The
      shell of the capsule is fabricated by alternate adsorption of oppositely charged
      polyelectrolytes (PEs) onto the surface of colloidal particles. Cores of
      different nature (organic or inorganic) with size varied from 0.1 to 10 mum can
      be used for templating such PE capsules. The shell thickness can be tuned in
      nanometer range by assembling of defined number of PE layers. The permeability of
      capsules depends on the pH, ionic strength, solvent, polymer composition, and
      shell thickness; it can be controlled and varied over wide range of substances
      regarding their molecular weight and charge. Including functional polymers into
      capsule wall, such as weak PEs or thermosensitive polymers, makes the capsule
      permeability sensitive to correspondent external stimuli. Permeability of the
      capsules is of essential interest in diverse areas related to exploitation of
      systems with controlled and sustained release properties. The envisaged
      applications of such capsules/vesicles cover biotechnology, medicine, catalysis,
      food industry, etc.

PMID- 15571663
TI  - Phospholipid mesophases at solid interfaces: in-situ X-ray diffraction and spin
      label studies.
AB  - In this work, we report on recent investigations, both on the global and on the
      local molecular architecture of supported phospholipid model membranes. A brief
      theoretical introduction explains how global structural information on
      supramolecular lipid ensembles can be retrieved from surface X-ray diffraction
      measurements as well as how spin-label electron paramagnetic resonance
      spectroscopy (EPR) provides complementary information on the local environment of
      probe molecules. The combination of especially designed X-ray cells with the
      technique of small- and wide-angle X-ray surface scattering makes it possible to
      explore various fields of lipid research and its applications. Examples for
      different physico-chemical conditions are presented: (i) in situ chemistry under
      excess of water conditions demonstrating how solid-supported lipid films sense
      salinity, (ii) the 3D electron density reconstruction of a vesicle-fusion
      intermediate under controlled humidity, and (iii) complementary temperature and
      pressure effects on oriented phospholipid samples. Further, special attention has
      been given to the influence of different film preparation techniques with respect
      to quality and the defect structure manifestation. To resolve the proportions and
      local properties of defects in a hydrated lipid-deposited surface, spin-label EPR
      was applied. The results from 9.6 GHz EPR as well as from 1.2 GHz EPR suggest the
      alignment to be in the range between 30% and 80%. In addition, slow time
      dependent EPR measurements point to nano-structural rearrangements due to water
      flow and reduction of alignment quality.

PMID- 15571664
TI  - Interfacially formed organized planar inorganic, polymeric and composite
      nanostructures.
AB  - This paper discusses synthetic strategies for fabrication of new organized planar
      inorganic, polymeric, composite and bio-inorganic nanostructures by methods based
      on chemical reactions and physical interactions at the gas-liquid interface,
      Langmuir monolayer technique, interfacial ligand exchange and substitution
      reactions, self-assembling and self-organization processes, DNA templating and
      scaffolding. Stable reproducible planar assemblies of ligand-stabilized molecular
      nanoclusters containing definite number of atoms have been formed on solid
      substrate surfaces via preparation and deposition of mixed Langmuir monolayers
      composed by nanocluster and surfactant molecules. A novel approach to synthesis
      of inorganic nanoparticles and to formation of self-organized planar inorganic
      nanostructures has been introduced. In that approach, nanoparticles and
      nanostructures are fabricated via decomposition of insoluble metal-organic
      precursor compounds in a layer at the gas-liquid interface. The ultimately thin
      and anisotropic dynamic monomolecular reaction system was realized in that
      approach with quasi-two-dimensional growth and organization of nanoparticles and
      nanostructures in the plain of Langmuir monolayer. Photochemical and redox
      reactions were used to initiate processes of interfacial nucleation and growth of
      inorganic phase. It has been demonstrated that morphology of resulting inorganic
      nanostructures can be controlled efficiently by variations of growth conditions
      via changes in state and composition of interfacial planar reaction media, and by
      variations of composition of adjacent bulk phases. Planar arrays and chains of
      iron oxide and ultrasmall noble metal (Au and Pd) nanoparticles, nanowires and
      new organized planar disk, ring, net-like, labyrinth and very high-surface area
      nanostructures were obtained by methods based on that approach. Highly organized
      monomolecular polymeric films on solid substrates were obtained via deposition of
      Langmuir monolayer formed by water-insoluble amphiphilic polycation molecules.
      Corresponding nanoscale-ordered planar polymeric nanocomposite films with
      incorporated ligand-stabilized molecular metallic nanoclusters and interfacially
      grown nanoparticles were fabricated successfully. Novel planar DNA complexes with
      amphiphilic polycation monolayer were formed at the gas-aqueous phase interface
      and then deposited on solid substrates. Toroidal and new net-like conformations
      were discovered in those complexes. Nanoscale supramolecular organization of the
      complexes was dependent on cationic amphiphile monolayer state during the DNA
      binding. These monolayer and multilayer DNA/amphiphilic polycation complex
      Langmuir-Blodgett films were used as templates and nanoreactors for generation of
      inorganic nanostructures via metal cation binding with DNA and following
      inorganic phase growth reactions. As a result, ultrathin polymeric nanocomposite
      films with integrated DNA building blocks and organized inorganic semiconductor
      (CdS) and iron oxide quasi-linear nanostructures were formed. It has been
      demonstrated that interaction of deposited planar DNA/amphiphilic polycation
      complexes with bulk phase colloid inorganic cationic ligands (CdSe nano-rods) can
      result in formation of new highly organized hybrid bio-inorganic nanostructures
      via interfacial ligand exchange and self-organization processes. The methods
      developed can be useful for investigation of fundamental mechanisms of nanoscale
      structural organization and transformation processes in various inorganic and
      molecular systems including bio-molecular and bio-inorganic nanostructures. Also,
      those methods are relatively simple, environmentally safe and thus could prove to
      be efficient practical instruments of molecular nanotechnology with potential of
      design and cost-effective fabrication of new controlled-morphology organized
      planar inorganic and composite nanostructured materials. Possible applications of
      obtained nanostructures and future developments are also discussed.

PMID- 15571665
TI  - Flocculation of cellular suspensions by polyelectrolytes.
AB  - The regularities, kinetics and mechanisms of flocculation of Escherichia coli and
      B. thuringiensis var. israelensis (Bti) cellular suspensions by water-soluble
      polymers-and first of all cationic polyelectrolytes of different charge density
      and stiffness of the macromolecule chain have been investigated. The effect of
      the focculant dose and nature, its charge density, the hydrophobic-hydrophilic
      balance in macromolecule, the suspension concentration, the mode of adding the
      reagent, the pH and the medium composition on the degree of aggregation of cells
      both in perikinetic regime and in a flowing system is considered. It has been
      shown that the main laws of microorganism's suspension flocculation are the same
      as the laws of flocculation of inorganic dispersions but at the same time the
      first process is much more complicated because the cell-flocculant interactions
      are strongly affected by products of cell metabolism, components of the culture
      liquor, pH value, electrolyte content as well as by the changing structure of the
      cell surface. On the basis of complex measurements of polymer adsorption and its
      effect on the electrokinetic potential and degree of aggregation of cells, a
      conclusion is made that the aggregation of E. coli cells by flexible
      polyelectrolytes like polydiethylaminoethylmetacrylate and its copolymers with
      acrylic acid, acrylamide and vinylpyrrolidone is due to charge neutralization,
      while the flocculation in the presence of rigid-chain chitosan and its
      derivatives is caused mainly by "bridging" between cells via adsorbed
      macromolecules. Extraction of cells from suspension can be enhanced by
      combination of electroflotation and flocculation by cationic polyelectrolytes. It
      has been shown that dilute suspensions of Bti bacteria can be effectively
      flocculated and concentrated using different cationic and anionic
      polyelectrolytes that is necessary for its formulation and use as anti-mosquito
      agent.

PMID- 15571666
TI  - Evidence for thermoregulation by dopamine D1 and D2 receptors in the
      anteroventral preoptic region during normoxia and hypoxia.
AB  - Hypoxia causes a regulated decrease in body temperature (Tb), a response that has
      been called anapyrexia. Stimulation of dopamine receptors in the central nervous
      system (CNS) reduces Tb in rats, and dopamine D1 and D2 receptors seem to be
      involved in this response. Thus, we predicted that injection of SCH 23390 and
      haloperidol, D1 and partly D2 receptor antagonists, respectively, into the
      anteroventral preoptic region (AVPO, the thermointegrative region of the CNS)
      would lessen the hypoxia-induced anapyrexia. We measured Tb of conscious Wistar
      rats before and after injection of SCH 23390 (50 and 100 ng/100 nl) or
      haloperidol (50 e 500 ng/100 nl) or their respective vehicles (saline and DMSO
      5%) into the AVPO followed by 30 min of hypoxia (7% O2). Vehicles and the lower
      doses of SCH 23390 and haloperidol had no effect on Tb during normoxia or
      hypoxia. The higher doses of SCH 23390 and haloperidol attenuated (P<0.05) the
      drop in Tb elicited by hypoxia. However, this higher haloperidol dose also
      increased Tb during normoxia. The present data is consistent with the notion that
      dopamine is an important thermoregulatory neurotransmitter in a way that D2
      receptors are mainly involved with maintenance of Tb in euthermia, while D1
      receptors are activated to induce hypoxic anapyrexia in the AVPO.

PMID- 15571667
TI  - Characterization of regional cerebral blood flow and expression of angiogenic
      growth factors in the frontal cortex of juvenile male SHRSP and SHR.
AB  - Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral
      disorder associated with male preponderance and reduction of regional cerebral
      blood flow (rCBF). However, lack of an appropriate animal model exhibiting
      appropriate AD/HD symptoms stands in the way of studying mechanism(s) underlying
      reduced rCBF and male preponderance. Our group has been investigating the
      suitability of juvenile male stroke-prone spontaneously hypertensive rats
      (SHRSP), a substrain of the commonly used AD/HD animal model SHR, as a model for
      AD/HD because, unlike SHR, SHRSP displays cognitive impairment and male
      preponderance. Our more recent studies revealed alterations in the synthesis of
      sex steroid hormones and angiogenic factors in the frontal cortex of male SHRSP
      compared to the genetic control WKY. Based on these observations, the present
      study utilizes laser-Doppler flowmetry, histochemistry, enzyme immunoassay,
      immunoblotting, and real-time PCR to characterize and compare the patterns of
      regional cerebral blood flow and synthesis of angiogenic molecules [basic
      fibroblast growth factor; nitric oxide synthase isoforms (endothelial, neuronal
      and inducible); vascular endothelial growth factor (VEGF) and its signaling
      molecules (VEGF receptors, phosphorylated Akt, endothelial nitric oxide synthase
      eNOS] between male SHRSP and SHR. Overall, consistent with our previous data
      showing alteration in VEGF/Akt/NO signaling, there was a marked reduction in the
      profile of rCBF (35%) and angiogenic factors of SHRSP, compared to age-matched
      genetic control Wistar-Kyoto rats (WKY) and SHR. We conclude that, unlike SHR,
      the profiles of rCBF and angiogenic factors in SHRSP are altered in juvenile
      male. Thus, SHRSP appears to be a more suitable animal model for studying changes
      in rCBF in AD/HD.

PMID- 15571668
TI  - Evidence for paracrine modulation of voltage-dependent calcium channels by
      amperometric analysis in cultured porcine adrenal chromaffin cells.
AB  - We investigated the endogenous control through vesicular contents of voltage
      dependent Ca2+ channels (VDCCs) in cultured porcine adrenal chromaffin cells. To
      examine paracrine regulation of VDCCs, catecholamine release was monitored
      amperometrically together with patch-clamp recording under culture conditions at
      different cell densities. A depolarizing pulse evoked Ca(2+)- (ICa) and Ba(2+)
      currents (IBa) in Ca(2+)- and Ba(2+)-containing solutions, respectively. In cells
      cultured at high density, stop-flow of the external solution decreased the I(Ba)
      concomitant with a sustained increase of amperometric current (Iamp), but not in
      cells at low density, suggesting the endogenous modulation of VDCCs in a paracine
      fashion. The degree of the prepulse facilitation was similar regardless of the
      flow condition. Application of noradrenaline (NA), ATP, methionine-enkephalin
      (ENK) or protons decreased IBa. The extent of the prepulse facilitation of the
      endogenous VDCC inhibition was similar to those induced by NA and ATP. GDPbetaS,
      pertussis toxin (PTX), blockers for alpha-adrenoceptors and P2-purinoceptors
      significantly reduced the endogenous VDCC inhibition. These results suggest that
      VDCCs are regulated by vesicular substances in a paracrine fashion, at least by
      noradrenaline and ATP, through activation of alpha-adrenoceptors and P2
      purinoceptors, respectively, in porcine adrenal chromaffin cells.

PMID- 15571669
TI  - Prolonged initiation latency in Morris water maze learning in rats with ibotenic
      acid lesions to medial striatum: effects of systemic and intranigral muscimol
      administration.
AB  - The contribution of the rat striatonigral GABAergic system to spatial navigation
      was investigated in this study. We first tested the effects of ibotenic acid
      lesions of the striatum on place navigation performance in Morris water maze.
      Medial but not lateral striatal lesions produced a significant increase of escape
      latency, and this deficit was clarified as mainly caused by a marked increase of
      initiation latency rather than of thigmotaxis time (experiment 1). Next we tested
      the effects of systemic (0.5 mg/kg) and intranigral (2.0 ng/side) administrations
      of muscimol, a GABA receptor agonist, on the place navigation deficits produced
      by medial striatal lesions. Systemic muscimol administration significantly
      ameliorated the increase of initiation latency, while intranigral administration
      was not sufficiently effective (experiment 2). The results suggest that neural
      circuits containing medial striatal neurons play an essential role in place
      navigation performance probably through some movement preparation processes that
      precede movement execution, and the GABAergic system may be involved in this
      initiation process, although whether it is the striatonigral GABAergic system
      that is involved remains unclear.

PMID- 15571670
TI  - The 5HT1A receptor agonist, 8-OH-DPAT, protects neurons and reduces astroglial
      reaction after ischemic damage caused by cortical devascularization.
AB  - Serotonin 1A (5HT1A) receptor agonists have shown neuroprotective properties in
      different models of central nervous system injury. Activation of neuronal 5HT1A
      receptors appears to be involved in the neuroprotective effects. It remains to be
      elucidated if astroglial cells are responsive to the 5HT1A neuroprotective
      effects. The participation of astroglial S100B trophic factor has been proposed
      since 5HT1A activation leads to S100B release and nanomolar concentration level
      of this molecule showed pro-survival activity in neuronal cultures. Using the
      cortical devascularization model (CD; unilateral pial disruption), a procedure
      that results in localized ischemia without producing direct physical damage to
      brain tissue, we tested the effects of a full 5HT1A agonist, 8-OH-DPAT, or the
      antagonist WAY-100635 on cortical neuronal survival, astroglial cell response and
      S100B expression. Wistar rats were subjected to CD lesion which consisted of a
      craniotomy followed by physical damage to the underlying pial blood vessels. Two
      and twenty-four hours after the CD lesion, animals received intraperitoneally 8
      OH-DPAT (1 mg/kg), WAY-100635 (1 mg/kg) or vehicle (sterile saline). At 3, 7 or
      14 days post-lesion, animals were sacrificed and their brains processed for
      immunohistochemistry to detect GFAP, vimentin, MAP-2, S100B and nuclear Hoechst
      staining. S100B level in the brain cortex and serum was quantified by an ELISA
      assay. Serum S100B was considered an index of S100B release. 8-OH-DPAT treatment
      reduced neuronal death, dendrite loss, astroglial hypertrophy and hyperplasia. In
      contrast, WAY-100635 treatment increased these parameters of damage. S100B
      intracellular immunoreactivity in astrocytes and total S100B level showed long
      lasting changes after the CD lesion and subsequent treatments depending on the
      5HT1A activity. The level of serum S100B was increased in 8-OH-DPAT-treated
      animals. Increased damage observed in WAY-100635-treated animals supports the
      hypothesis that the protective 8-OH-DPAT action may be mediated by specific 5HT1A
      receptors. The reduction in astroglial hypertrophy and hyperplasia as well as
      long-term changes in S100B immunoreactivity and increased S100B release that we
      observed allows us to hypothesize that astroglial cells may play an important
      role in 5HT1A-mediated neuroprotection.

PMID- 15571671
TI  - Immunohistochemical mapping of calcitonin receptors in the adult rat brain.
AB  - Calcitonin receptors (CTR) have previously been identified in specific regions of
      the rat central nervous system using in situ hybridization or autoradiography
      with iodinated ligands. In this study, the results of immunohistochemical mapping
      of CTR in the adult rat brain are reported, using a potent and recently developed
      antibody that recognizes an intracellular epitope of the rat CTR, and high
      resolution immunofluorescence techniques. Abundant expression was found in the
      brain, with highest densities in the nucleus accumbens, lateral arcuate nucleus,
      lateral substantia nigra, bed nucleus of the stria terminalis, locus coeruleus,
      area postrema, nucleus of the solitary tract, and some of the nuclei of the
      reticular formation. These results are in close correspondence with previous
      mapping studies. However, we detected CTR immunoreactivity in several additional
      brain areas, as the ventromedial, lateral and posterior hypothalamus, where CT
      binding has not yet been described. Our detailed mapping of the CTR in the rat
      brain has identified CTR-positive cells that will be important for subsequent
      characterization of behavioral functions associated with the actions of CT
      related peptides.

PMID- 15571672
TI  - Glutamate N-methyl-D-aspartate and dopamine receptors have contrasting effects on
      the limbic versus the somatosensory cortex with respect to amphetamine-induced
      neurodegeneration.
AB  - The roles that glutamate N-methyl-D-aspartate (NMDA) and dopamine D1-like and D2
      like receptors play in the cortical neurotoxicity occurring in rats exposed to
      multiple doses of amphetamine (AMPH) for 2 days was evaluated. Neurodegeneration
      in rats that did not become hyperthermic during AMPH exposure was quantified by
      counting isolectin B4-labeled phagocytic microglia and Fluoro-Jade (F-J)-labeled
      neurons in the somatosensory parietal cortex, piriform cortex and posterolateral
      cortical amygdaloid nucleus (PLCo). The NMDA receptor antagonist, dizocilpine
      (0.63 mg/kg day) blocked AMPH-induced neurodegeneration in the somatosensory
      cortex. However, it did not affect degeneration in the piriform cortex and PLCo
      indicating that limbic degeneration was not NMDA-mediated. The dopamine
      antagonists, eticlopride (D2/3, 0.25 mg/kg day) and SCH-23390 (D1, 0.25 mg/kg
      day), blocked the stereotypic behavior and neurodegeneration in the somatosensory
      cortex. However, eticlopride had a lesser protective effect in the limbic
      regions. As well, the dopamine D2/D3 agonist quinpirole (1.5 mg/kg day) protected
      against cortical neurodegeneration when it was given during AMPH exposure and
      continued until sacrifice. The dopamine D1 agonist (SKF-38393, 12.5 mg/kg day)
      had no significant effect on neurodegeneration. These data indicate that there
      are significant differences in NMDA and dopamine D2 modulation of AMPH-induced
      neurodegeneration in the somatosensory cortex compared to the limbic cortices,
      and limbic cortical degeneration is not necessarily dependent on excessive
      stimulation of NMDA receptors as it is in the somatosensory cortex. Although
      excessive dopamine receptor stimulation during amphetamine exposure may trigger
      the neurodegenerative processes, continued D2 stimulation after AMPH exposure is
      neuroprotective in the cortex.

PMID- 15571673
TI  - Involvement of kappa-opioid receptors and sigma receptors in memory function
      demonstrated using an antisense strategy.
AB  - Although antinociceptive effects of U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl
      N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulfonate and (-)
      pentazocine have been reported to influence kappa-opioid receptors, the
      involvement of kappa-opioid receptors in learning and/or memory is still
      controversial. We have recently reported that the memory improving effect of (-)
      pentazocine was antagonized by sigma1 receptor antagonist. In this study, we
      examined the effects of several antisense oligodeoxynucleotides (antisenses) to
      kappa1-opioid receptors and sigma1 receptor on memory and nociceptive function.
      Male ddY mice were treated subcutaneously (s.c.) with scopolamine (1.65 mumol/kg)
      and/or test drugs 30 min before a Y-maze test. U-50,488H significantly improved
      the scopolamine-induced impairment of spontaneous alternation behavior. Twenty
      micrograms of antisense targeting exons 2 and 3 of the kappa1-opioid receptor
      significantly reversed the effects of U-50,488H, but antisense targeting exon 1
      and mismatch sense did not. The antisense targeting exon 3 was most effective.
      These antisenses themselves did not affect normal mice, indicating that kappa1
      opioid receptors do not tonically regulate memory function. All three antisenses
      equally prevented U-50,488H-induced antinociceptive effects in the acetic-acid
      induced writhing test. Pretreatment with antisense targeting sigma1 receptors (AS
      sigma1) completely prevented the memory-improving effects of (-)- and (+)
      pentazocine, although U-50,488H ameliorated the scopolamine-induced impairment of
      spontaneous alternation behavior in AS-sigma1-treated mice. These results suggest
      that kappa1-opioid receptors containing different exons have a distinct function
      in memory and nociceptive functions. Furthermore, kappa-opioid receptors agonist
      showing analgesic effects act on kappa-opioid receptors or sigma receptors and
      play important roles only when memory function is impaired, but the two neuronal
      systems regulate memory function independently.

PMID- 15571674
TI  - Differences between primary somatosensory cortex- and vertex-derived
      somatosensory-evoked potentials in the rat.
AB  - The somatosensory-evoked potential (SEP) elicited by high-intensity stimulation
      potentially provides a reliable indicator of analgesic efficacy since it reflects
      the level of activation of the nociceptive system. In the present study,
      components in the 10-30-ms latency range of SEPs recorded over the primary
      somatosensory cortex (SI-SEPs) and vertex (Vx-SEP) in the rat were characterized
      and compared. SEPs were elicited by electrical tail-base stimulation, and SI-SEPs
      and Vx-SEPs were recorded simultaneously. Responses to increasing stimulus
      intensity and stimulus frequency while awake and responses to bolus injection of
      fentanyl, thiopental, and ketamine were investigated. The SI-SEP positive
      component (P) occurring at 12 ms after stimulation (P12) showed a significantly
      lower intensity threshold and was significantly less affected by increasing
      stimulus frequency and by administration of the different drugs when compared to
      the Vx-SEP P15. The fact that a single stimulus modality results in different
      signal characteristics dependent on the recording site supports the view that
      different neural mechanisms involved in primary processing of somatosensory
      information are responsible for the generation of the SI-SEP P12 and Vx-SEP P15,
      respectively. This differentiation between SI-SEPs and Vx-SEPs potentially has
      distinct consequences using the SEP to evaluate nociception and analgesia in the
      rat model.

PMID- 15571675
TI  - Brain differences in newborn rats predisposed to helpless and depressive
      behavior.
AB  - Inborn brain differences in metabolic capacity were mapped in congenitally
      helpless rats, a genetically selected strain predisposed to show helpless and
      depressive behavior. There are a number of brain regions showing abnormal
      metabolism in adult congenitally helpless rats. Some of these alterations may be
      innate while others may be due to environmental factors, such as maternal care
      and postnatal stress. To identify which brain structures show innate differences,
      brains of newborn rats from congenitally helpless and non-helpless strains were
      compared using cytochrome oxidase histochemistry, an endogenous marker of
      regional metabolic capacity. A smaller subset of regions affected in adults
      showed significantly less metabolic activity in the newborn brains, including
      paraventricular hypothalamus, habenula, hippocampus, subiculum, lateral septal
      nucleus, anterior cingulate cortex, infralimbic cortex, and medial orbitofrontal
      cortex. A covariance analysis further revealed a striking reduction of functional
      connectivity in the congenitally helpless brain, including a complete decoupling
      of limbic forebrain regions from midbrain/diencephalic regions. This pattern of
      brain metabolism suggests that helplessness vulnerability is linked to altered
      functioning of limbic networks that are key to controlling the hypothalamic
      pituitary-adrenal axis. This implies that vulnerable animals have innate deficits
      in brain systems that would normally allow them to cope with stress, predisposing
      them in this manner to more readily develop helpless and depressive behaviors.

PMID- 15571676
TI  - Strain and sex differences in the expression of nociceptive behavior and stress
      induced analgesia in rats.
AB  - Evidence indicates that genetic, gender, and emotional/attentional aspects
      modulate the pain sensation. The present study examined the effect of swim-stress
      on nociceptive responses in Lewis (LEW) and spontaneously hypertensive (SHR)
      inbred rats (contrasting for anxiety-related behaviors), as well as in Wistar
      (WIS) rats of both sexes. Furthermore, we explored possible neurochemical
      mechanisms involved. In addition, we investigated whether habituation in the hot
      plate apparatus could modify the hypoalgesic phenotype of SHR. Male and female
      LEW, SHR, and WIS rats were tested immediately before and 2 min after a 3-min
      swim in 15 degrees C water. The swim-stress induced analgesia in LEW and WIS, but
      not in SHR male rats. The same stressor induced analgesia in females of all three
      strains. In WIS female rats, the stress-induced analgesia (SIA) seems to involve,
      at least partially, a nonopioid N-methyl-d-aspartate (NMDA) analgesic system.
      Moreover, five brief exposures (90 s; 10-min intertrial interval) to the unheated
      hot-plate apparatus completely abolished the differences in basal hot-plate
      latencies observed in SHR compared with LEW and WIS strains. The present results
      demonstrate genetic and gender differences in nociceptive sensitivity and in the
      activation of endogenous analgesic systems in rats and highlight the influence of
      emotional reactivity. The SHR's hypoalgesic phenotype seems to involve central
      cognitive processes. Therefore, the LEW and SHR inbred strains may provide an
      important tool for study of the molecular bases underlying nociception and its
      modulation and the relationship with emotional/attentional processes.

PMID- 15571677
TI  - Integration of neural responses originating from different regions of the
      cortical somatosensory map.
AB  - The neural pathways responsible for detecting peripheral tactile stimuli are well
      known; however, the interactions between different somatosensory regions have
      been less well investigated. This study demonstrates how the contralateral
      sensory response of rat barrel cortex to whisker stimulation is affected by
      stimulation of contralateral forepaw and ipsilateral whisker and forepaw. The
      barrel cortex in the right hemisphere was located using optical imaging. A 16
      channel multielectrode was used to measure field potentials evoked by
      contralateral electrical stimulation of the whisker pad. A standard response in
      the right barrel cortex to single pulse electrical stimulation of the
      contralateral whisker pad was modulated by applying conditioning stimulation to
      one of three other regions of the body (the ipsilateral whisker pad, the
      ipsilateral or contralateral forepaws). In conditions where the standard
      contralateral whisker stimulus preceded the conditioning pulse, the size of
      response was identical to when it was stimulated alone. However, when the
      ipsilateral whisker and contralateral forepaw conditioning stimuli preceded the
      contralateral whisker pad stimulation, up to a 35% reduction in the contralateral
      whisker response was observed. These results confirm and extend previous studies
      [Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 11026-11031; J. Neurosci. 21 (2001)
      5251-5261], which show bilateral integration of neural activity within the rat
      somatosensory system. Furthermore, the longer latency of the inhibition following
      stimulation of the contralateral forepaw suggests the possible involvement of
      extracortical circuitry.

PMID- 15571678
TI  - Paraventricular nucleus neurons producing neurotensin after lipopolysaccharide
      treatment project to the median eminence.
AB  - Inflammation consists in secretion of cytokines that stimulate the hypothalamo
      pituitary-adrenal (HPA) axis to release the anti-inflammatory corticosterone.
      Upstream in this axis are corticotropin-releasing hormone (CRH) neurons in the
      paraventricular nucleus (PVN) whose multipeptidergic phenotype changes: both
      corticotropin-releasing hormone mRNAs and neurotensin mRNAs are up-regulated.
      Combining in situ hybridization with a retrograde neuronal marker, we
      demonstrated that neurotensin-containing neurons in the paraventricular nucleus
      project to the median eminence.

PMID- 15571679
TI  - p21(WAF1/Cip1) is not involved in kainic acid-induced apoptosis in murine
      cerebellar granule cells.
AB  - Kainic acid (KA) treatment induced neuronal death and apoptosis in murine
      cerebellar granule cells (CGNs) cultures from both wild-type and knockout p21(-/
      ) mice. There was not statistically significant difference in the percentage of
      neuronal apoptosis among strains. KA-induced neurotoxicity was prevented in the
      presence of NBQX (20 microM) and GYKI 52446 (20 microM), but not by z-VAD-fmk,
      suggesting that caspases are not involved in the apoptotic process. Data suggest
      that p21(WAF/Cip) was unable to modulate KA-induced apoptosis in murine CGNs.

PMID- 15571680
TI  - Biosorption of chromium(VI) and arsenic(V) onto methylated yeast biomass.
AB  - Yeast biomass was methylated in a 0.1 M HCl methyl alcohol solution at room
      temperature and the methylated yeast (MeYE) was applied to the adsorptive
      separation of Cr(VI) and As(V) anions from aqueous solutions. At near-neutral pH,
      while Cr(VI) and As(V) anions were scarcely adsorbed onto unmethylated yeast
      biomass, the amounts adsorbed increased with increasing methylation degree. The
      amount of Cr(VI) adsorbed onto MeYE was almost constant at pH 4-6 and decreased
      with increasing pH above pH 6. The amount of As(V) adsorbed onto MeYE was rather
      lower than that of Cr(VI) and it had a peak at about pH 7. A metal-binding model
      was used to describe the adsorption characteristics of Cr(VI) and As(V) on MeYE.
      The results showed that MeYE has two different types of adsorption sites. The
      saturated amount of Cr(VI) and As(V) adsorbed onto MeYE having methylation degree
      0.94 was 0.55 mmol g(-1).

PMID- 15571681
TI  - Application of the NICA-Donnan approach to calculate equilibrium between proton
      and metal ions with lignocellulosic materials.
AB  - The NICA (nonideal competitive adsorption)-Donnan model is employed to describe
      the interactions between Cu2+, Pb2+, Cd2+, Mn2+, and Fe3+ ions and the lignins
      extracted from wheat bran (lignocellulosic substrate, LS) and from kraft pulp
      (residual kraft lignin, RKL), and between Cu2+, Mn2+, and Fe3+ ions and wood
      fibers from kraft pulps. The charge of the LS and the fiber charge need to be
      obtained from potentiometric titration data for the LS, and by use of Donnan
      equilibrium, mass balance, and electroneutrality equations for the kraft fiber.
      The proton binding parameters for the LS and the kraft fiber, the total site
      densities (Qmax,1 and Qmax,2), the median protonation constants (K1 and K2), and
      nonideality-generic heterogeneity parameters (m1 and m2) (subscripts 1 and 2
      refer to the carboxyl and phenolic functional groups) are obtained by fitting
      these charge data. With the above proton parameters, the interactions between
      metal ions and the lignins (LS and RKL)/kraft fibers are calculated, and the
      metal binding parameters are obtained. These parameters are the binding constants
      of metal i (K(i,1) and K(i,2)), ion-specific nonideality parameters (n(i,1) and
      n(i,2)), and intrinsic heterogeneity parameters (p1 and p2). p1 and p2 are the
      same for all metal ions binding to a specific sorbent. Here, p1 and p2 values
      obtained by fitting the binding data of a specific metal ion are used directly in
      binding calculations for other metal ions, and do not need to be fitted. By use
      of the above parameters for single metal ion binding, the binding relationship
      between a mixed metal ion and lignocellulosic substrate/kraft fiber can be
      predicted.

PMID- 15571682
TI  - Adsorption and precipitation of an aminoalkylphosphonate onto calcite.
AB  - The mechanism of nitrilotris(methylenephosphonic acid) (H6NTMP)/calcite reaction
      was studied with a large number of batch experiments where phosphonic acid was
      neutralized with 0 to 5 equivalents of NaOH per phosphonic acid and the
      concentration ranged from about 10 nmol/L to 1 mol/L. It is proposed that the
      phosphonate/calcite reactions are characterized in three steps. At low
      phosphonate concentration (<1 micromol/L NTMP concentration), the
      phosphonate/calcite reaction can be characterized as a Langmuir isotherm. At
      saturation, only approximately 7% of the calcite surface is covered with
      phosphonate; presumably these are the kinks, step edges, or other imperfect
      sites. At higher phosphonate concentrations, the attachment is characterized by
      calcium phosphonate crystal growth to a maximum of four to five surface layer
      thick, with solid phase stoichiometry of Ca(2.5)HNTMP and a constant solubility
      product of 10(-24.11). After multiple layers of phosphonate are formed on the
      calcite surface, the solution is no longer at equilibrium with calcite. Further
      phosphonate retention is probably due to mixed calcium phosphonate solid phase
      formation at lower pH and depleted solution phase Ca conditions. The proposed
      mechanism is consistent with phosphate/calcite reaction and can be used to
      explain the fate of phosphonate in brines from oil producing wells and the
      results are compared with two oil wells.

PMID- 15571683
TI  - Adsorption of NH3 onto activated carbon prepared from palm shells impregnated
      with H2SO4.
AB  - Adsorption of ammonia (NH3) onto activated carbons prepared from palm shells
      impregnated with sulfuric acid (H2SO4) was investigated. The effects of
      activation temperature and acid concentration on pore surface area development
      were studied. The relatively large micropore surface areas of the palm-shell
      activated carbons prepared by H2SO4 activation suggest their potential
      applications in gas adsorption. Adsorption experiments at a fixed temperature
      showed that the amounts of NH3 adsorbed onto the chemically activated carbons,
      unlike those prepared by CO2 thermal activation, were not solely dependent on the
      specific pore surface areas of the adsorbents. Further adsorption tests for a
      wide range of temperatures suggested combined physisorption and chemisorption of
      NH3. Desorption tests at the same temperature as adsorption and at an elevated
      temperature were carried out to confirm the occurrence of chemisorption due to
      the interaction between NH3 and some oxygen functional groups via hydrogen
      bonding. The surface functional groups on the adsorbent surface were detected by
      Fourier transform infrared spectroscopy. The amounts of NH3 adsorbed by
      chemisorption were correlated with the contents of elemental oxygen present in
      the adsorbents. Mechanisms for chemical activation and adsorption processes are
      proposed based on the observed phenomena.

PMID- 15571684
TI  - Systematic studies on adsorption of lead on sea nodule residues.
AB  - Lead adsorption from aqueous solutions was studied with the aim of detoxifying
      industrial effluents before their safe disposal onto land or into river waters.
      Sea nodule residue (SNR), a waste material containing oxides and oxyhydroxides of
      manganese, iron, silicon, etc., was used as an effective adsorbent for lead in
      this study. The effect of various parameters such as contact time, initial lead
      concentration, pulp density, particle size of the adsorbent, pH, and temperature
      was studied to optimize the conditions for maximum adsorption. Adsorption
      followed first-order kinetics and 99% of lead adsorption was achieved at a
      solid:liquid ratio of 1:330, in the pH range 5.5-6.0 at a particle size of -150
      microm in 8 h for solution containing 200 ppm lead. The adsorption capacity was
      found to be 99.0 mg of lead per gram of SNR and the adsorption isotherms followed
      the Langmuir and Freundlich adsorption models. The mechanism of adsorption of
      lead onto the sea nodule residue was also investigated. It was possible to reduce
      the lead level from 25-200 ppm to acceptable levels (0.1 ppm) by adsorption over
      this solid waste.

PMID- 15571685
TI  - Crystallization and prevention of supercooling of microencapsulated n-alkanes.
AB  - Microencapsulated n-alkanes (n-octadecane, n-nonadecane, and n-eicosane) were
      synthesized by in situ polymerization using urea-melamine-formaldehyde polymer as
      shells. Microcapsules 5.0 and 10.0 wt% of 1-tetradecanol, paraffin, and 1
      octadecanol were used as nucleating agents. The fabrication was characterized
      using Fourier transform infrared, light microscopy, and scanning electron
      microscopy. The crystallization and prevention of supercooling of the
      microcapsules are studied using differential scanning calorimetry (DSC) and wide
      angle X-ray diffraction. The crystal system of the microencapsulated n-alkane is
      the same as that of the bulk. The enthalpies of the microcapsules containing 70
      wt% n-alkanes are approximately 160 J/g. The melting temperature of the n-alkanes
      in the microcapsule is the same as that in the bulk. There are multiple peaks on
      the DSC cooling curves that are attributed to liquid-rotator, rotator-crystal,
      and liquid-crystal transitions. The DSC cooling behavior of microencapsulated n
      octadecane is affected by the average diameters. The measured maximum degree of
      supercooling of the microencapsulated n-octadecane is approximately 26.0 degrees
      C at a heating and cooling rate of 10.0 degrees C/min. The degree of supercooling
      of microencapsulated n-octadecane is decreased by adding 10.0 wt% of 1
      octadecanol as a nucleating agent.

PMID- 15571686
TI  - Surface characterization of cotton coated by a thin film of polystyrene with and
      without a cross-linking agent.
AB  - Thin polystyrene film coated on cotton was successfully formed by admicellar
      polymerization. Divinylbenzene (DVB) was used as a cross-linking agent to form
      networked polystyrene to improve film coverage. A wettability test and XPS
      analysis were used to characterize the coated surface. The optimum amount of DVB
      was around 1%. At this amount, the film coverage was most complete, as judged by
      the reduction of the O1s signal in XPS analysis.

PMID- 15571687
TI  - Aggregation of hydrophobically modified polysaccharides in solution and at the
      air-water interface.
AB  - The present article focuses on the comparative study of physicochemical
      properties of two ionic pullulan derivatives modified by 10 or 35 C8 chains per
      100 anhydroglucose units, named CMP10C8 and CMP35C8, respectively. In aqueous
      solutions, these derivatives exhibited an associative behavior as evidenced by
      pyrene fluorescence spectroscopy. This phenomenon, which stems from intra- and/or
      intermolecular interactions between the hydrophobic groups grafted on the polymer
      backbone, results in the formation of more or less condensed aggregates depending
      on the C8 ratio and the ionic strength of the media. The hydrophobically modified
      pullulans also displayed surface properties. Their adsorption at the air-solution
      interface was assessed from surface tension measurements. The results showed that
      both hydrophobized polymers adsorb in a coil conformation occupying a large
      interfacial molecular area. The comparison of these molecular areas indicated
      that CMP35C8 adopts a more shrunken conformation at the interface than CMP10C8,
      due to stronger intramolecular interactions. The stability of the adsorbed
      monolayer under bulk dilution was investigated by ellipsometric measurements.
      Whereas bulk dilution had no effect on the stability of the adsorbed CMP35C8
      film, it provoked significant changes in the adsorbed CMP10C8 monolayer. The
      stability of the CMP35C8 monolayers was attributed to the existence of
      intermolecular associations between the adsorbed coils.

PMID- 15571688
TI  - Assessing the effect of latex particle size and distribution on the rheological
      and adhesive properties of model waterborne acrylic pressure-sensitive adhesives
      films.
AB  - The adhesive and rheological properties of model acrylic pressure-sensitive
      adhesive (PSA) films prepared from high solid emulsions with different particle
      sizes and distributions have been investigated with a customized probe tack
      apparatus. For each emulsion, the monomer composition and gel content were kept
      constant but different average particle sizes and distributions were used.
      Adhesive films 100 microm thick were then prepared from these emulsions and their
      rheological properties in the linear regime and adhesive properties were
      systematically characterized. Surprisingly, both the rheological and adhesive
      properties were found to be very dependent on the initial latex particle size
      distribution. A series of experiments were carried out to assess the adhesive
      properties of films made from blends of small- and large-particle-size latexes.
      Using the probe tack test, a maximum in adhesion energy of the dry films was
      found for 60% of small particles in the blend, a composition clearly different
      from that giving a minimum viscosity of the latex implying that optimizing for
      properties may not be equivalent to optimizing for processing in these adhesive
      applications. Finally, the adhesive properties of two multimodal latexes with
      different particle size distributions were investigated. Both gave significantly
      higher adhesion energies and clear evidence of a fibrillar detachment process.
      This important result suggests that the spatial distribution of gel domains in
      the dry film and the molecular connectivity between those gel domains also play
      an important role in controlling its adhesive properties.

PMID- 15571689
TI  - Effects of surface properties of colloidal silica particles on redispersibility
      and properties of acrylic-based polyurethane/silica composites.
AB  - Nanosilica particles with different surface properties were designed and prepared
      using colloidal silica particles and four different qualitative silane coupling
      agents (SCA), namely methyltriethoxysilane (MTES), octyltriethoxysilane (OTES),
      vinyltriethoxysilane (VTES) and methacryloxypropyltrimethoxysilane (MATMS), and
      further applied in acrylic resins and corresponding polyurethane coats by in situ
      polymerization. It was found that different qualitative SCA molecules had very
      different impacts on the redispersibility of nanosilica particles, the adsorbed
      acrylic polyol molecules, the viscosities of acrylic polyol/silica hybrid resins,
      and the properties of acrylic-based polyurethane/silica composites.

PMID- 15571690
TI  - A bimodal particle dynamics model considering coagulation, coalescence and
      surface growth, and its application to the growth of titania aggregates.
AB  - A simple bimodal particle dynamics model was proposed to describe a particle
      system undergoing simultaneous particle formation, coagulation, coalescence, and
      surface growth. We extended our previous bimodal model, which used two discrete
      modes, to account for the surface growth of nonspherical particles. Surface
      reaction from TiCl4 was considered and its effects on the formation and growth of
      TiO2 particles were investigated. Simulation results of the present bimodal model
      considering surface growth showed very good agreement with those of the moving
      sectional model for the growth of spherical TiO2 in the literature. Surface
      growth of TiO2 aggregates was also simulated by using this bimodal model and a
      new design diagram indicating the significance of surface reaction of TiCl4 was
      proposed.

PMID- 15571691
TI  - Centrifugation equilibrium for spheres and spherocylinders.
AB  - The centrifugation equilibrium problem is formulated and solved using a new
      procedure in which the specified variables are the temperature, system volume,
      particle dimensions and concentrations, angular speed, cell length, and cell
      distance from the rotation axis. As a result, we obtain the concentration
      profiles for all types of particles present in the system, which are considered
      to be immersed in a fluid. The particles are modeled as hard nonattractive
      spherocylinders using an equation of state, but the procedure is not restricted
      to any geometrical shape, and can be used with any equation of state available.
      The fluid is treated as a continuous medium, responsible for centrifugal
      buoyancy. We make calculations for colloidal suspensions of silica, often used
      for separations in biotechnology. Results are in good agreement with experiments
      and show excellent agreement in comparison with Monte Carlo simulations. Our
      calculations also predict focusing and shifting phenomena that have been
      experimentally observed in separations of fine particles.

PMID- 15571692
TI  - Magnetic birefringence of minerals.
AB  - The earliest reports of magnetically induced optical birefringence included data
      for liquids, magnetic fluids and colloidal suspensions. Recent work has shown
      that with relatively straightforward apparatus, when carefully designed and
      aligned, measurable effects can be recorded even for suspensions of relatively
      weak diamagnetic materials, including mineral particles. By recording the
      magnitude of the birefringence induced in magnetic fields of up to two Tesla, a
      method for the analysis of the magnetic and optical characteristics of these
      diamagnetic colloids is evidenced. The principles, apparatus and methodology
      involved are described and novel data reported for the minerals attapulgite,
      bentonite, hectorite, kaolinite, montmorillonite and vermiculite. Preliminary
      experiments using pulsed fields on vermiculite sols show that, in favourable
      circumstances, estimates of particle size can be made by analysing signal
      response rates.

PMID- 15571693
TI  - The magnetic field influence on the polymorph composition of CaCO3 precipitated
      from carbonized aqueous solutions.
AB  - One of the most debated effects the magnetic fields exert on aqueous solutions
      and dispersions is their influence on the crystal structure of the main scale
      component, CaCO3. This study presents the results of an experimental program
      performed to quantitatively evaluate influence of the key magnetic treatment
      parameters--magnetic induction, exposure time, and fluid velocity--on the
      polymorph composition of CaCO3, precipitated from carbonized aqueous solutions.
      The results show that magnetic treatment favored the precipitation of aragonite.
      The key treatment parameters affecting the aragonite content were the magnetic
      induction and the exposure time, while the fluid velocity exerted no significant
      influence. The magnetic field has no significant influence on the zeta potential
      of the precipitated particles in any stage of the treatment. These experimental
      findings indicate that the magnetic field influence on the crystal structure of
      CaCO3 cannot be attributed to the magnetohydrodynamic influence on the charge
      distribution within the electrical double layer of the forming crystallites. The
      results rather suggest that the magnetic fields influence the CaCO3 polymorph
      phase equilibrium either by influencing the CO2/water interface or through the
      hydration of CO3(2-) ions prior to the formation of stable crystal nuclei in the
      solution.

PMID- 15571694
TI  - Dispersion of alumina-coated TiO2 slurries in the presence of poly(acrylic) acid
      influence of monovalent counterions.
AB  - The rheological behavior of concentrated alumina-coated TiO2 slurries has been
      investigated in connection with the type of surface counterions (monovalent
      cations: X = Li+, Na+, TMA+) in the absence and in the presence of polyacrylic
      acid (PAA). The study has been conducted in a pH range of 4-10 and with ionic
      strengths lower than 0.01 M. The pH and ionic strength were adjusted with XOH and
      XCl, respectively. The surface properties have been investigated by titration of
      surface counterions and the apparent yield stress has been measured using a
      dynamic stress rheometer. It appears from the results that the pH at the maximum
      yield stress and the magnitude of the yield stress depend on the nature of the
      counterion. The yield stress measurements were also conducted in the presence of
      PAA (0.5 segment/nm2) adsorbed on the particle surface. In that case, the mineral
      surface and adsorbed polymer were neutralized with XOH. The results show that the
      dispersion efficiency depends on the polymer counterion. In general, it is found
      that the maximum yield stress and the corresponding counterion surface density
      both follow the sequence TMA+ < Na+ < Li+. The adsorption of PAA apparently
      amplifies the effects observed with the corresponding cation. An electrostriction
      effect of the hydration layer at the interface is suggested in order to explain
      the increasing yield stress as the surface density of Li+ increases. The so
      called structure-making/structure-breaking model explains the yield stress
      reduction with the TMA+ surface density.

PMID- 15571695
TI  - Impedance analysis of an electrode-separated piezoelectric sensor as a surface
      monitoring technique for gelatin adsorption on quartz surface.
AB  - The early events pertaining to gelatin adsorption and desorption onto quartz
      surfaces were studied, employing an electrode-separated piezoelectric sensor
      (ESPS). The adsorption of gelatin on a quartz crystal surface corresponds to a
      mass increase, which can be monitored in real time by the changes in the
      impedance parameters of the ESPS. It was shown that the adsorption of gelatin on
      a quartz surface is partly irreversible with respect to the dilution of the bulk
      phase. The observed adsorption kinetics is compatible with a mechanism that
      involves adsorption, desorption, and transformation from a reversible adsorption
      state to irreversible one. A progressive approach method was established to
      simulate the adsorption process. The adsorption densities and kinetic parameters
      in the early adsorption process were obtained from the responses of the ESPS in
      the adsorption process. The influence of pH and ionic strength was tested. A
      comparison with the Langmuir adsorption model was made.

PMID- 15571696
TI  - Low-temperature reaction of trialkoxysilanes on silica gel: a mild and controlled
      method for modifying silica surfaces.
AB  - The room temperature reaction of 4-(triethoxysilyl)butyronitrile, 4-TBN
      ((C2H5O)3Si(CH2)3CN), on weakly hydrated silica samples pretreated at 393 K has
      been studied by desorption experiments and by diffuse reflectance infrared
      Fourier transform (DRIFT) spectroscopy at different aging times under various
      water partial pressures. The reaction is demonstrated by the decrease of
      desorption of 4-TBN with time and the simultaneous disappearance of the 2980 and
      1394 cm(-1) signals in the DRIFT spectra, assigned to the CH3 moiety of the
      ethoxy functions. Water partial pressure is shown to have a crucial effect on the
      rate and efficiency of the process as, after 6 days, for samples kept at room
      temperature under vacuum, ca. 50% of the silane has reacted, while for those kept
      in a water-saturated atmosphere the silane reaction reaches 96%. Although the
      silane appears to be irreversibly bonded to the surface, no definite conclusion
      may be drawn from these preliminary results as to the nature of the bonding
      (grafting or coating). These samples are compared to modified silicas prepared
      according to conventional methods. The same extent of silane reaction (50%) is
      achieved for preadsorbed samples kept under vacuum and either cured at 473 K for
      30 h or kept at room temperature for 6 days. A mild and controlled modification
      of silica by triethoxysilanes can thus be achieved by first physisorbing known
      amounts of the modifying silanes from an organic solvent on pretreated silica and
      then letting the samples mature for a few days at room temperature in a water
      saturated atmosphere.

PMID- 15571697
TI  - First insight into catalytic activity of anionic iron porphyrins immobilized on
      exfoliated layered double hydroxides.
AB  - Mg-Al layered double hydroxide (LDH) intercalated with glycinate anions was
      synthesized through co-precipitation and exfoliated in formamide and the single
      layer suspension was reacted with aqueous iron porphyrin solutions (Fe(TDFSPP)
      and Fe(TCFSPP)). The obtained materials were characterized by X-ray powder
      diffraction, UV-vis, and electron paramagnetic resonance and investigated in the
      oxidation reaction of cyclooctene and cyclohexane using iodosylbenzene as
      oxidant. The iron porphyrin seems to be immobilized at the surface of the
      glycinate intercalated LDH. The catalytic activities obtained in heterogeneous
      media for iron porphyrin, Fe(TDFSPP), was superior to the results obtained under
      homogeneous conditions, but the opposite effect was observed on the Fe(TCFSPP),
      indicating that, instead of the structural similarity of both iron porphyrins
      (second-generation porphyrins), the immobilization of each one produced different
      catalysts. The best catalytic activity of the Fe(TDFSPP)/Gly-LDH, compared to
      Fe(TCFSPP)/Gly-LDH, can be explained by the easy access of the oxidant and the
      substrate to the catalytic sites in the former, probably located at the surface
      of the layered double hydroxide pillared with glycinate anions. A model for the
      immobilization and a mechanism for the oxidation reaction will be discussed.

PMID- 15571698
TI  - Removal of toxic metals from wastewater by Brazilian natural scolecite.
AB  - The cation-exchange capacity of Brazilian natural zeolite, identified as
      scolecite, was studied with the aim of evaluating its applications in wastewater
      control. We investigated the process of sorption of chromium(III), nickel(II),
      cadmium(II), and manganese(II) in synthetic aqueous effluents, including sorption
      isotherms of single-metal solutions at 298, 313, and 333 K, by batch experiments,
      and the influence of pH on the process. The results have demonstrated that
      removal of metals from specific metal solutions is best described by a Freundlich
      isotherm, in which the values obtained for the Kf constants were in the following
      order: Cr > Mn > Cd > Ni. A Lagergren pseudo-second-order was the model that best
      described the sorption mechanism. The retention of metals was shown to be a
      function of the pH; the maximum binding capacity occurring at pH values around
      6.0. Thermodynamic data indicate the spontaneity of the endothermic cation
      exchange process. The values of Delta G0 suggest the following selectivity series
      at 298 K: Ni > Cr > Cd > Mn. The desorption process reaches equilibrium during
      the first 60 min of binding, suggesting that the mechanism involves specific
      sites located in the external surface of the scolecite.

PMID- 15571699
TI  - Preparation, structure, and magnetic properties of mesoporous magnetite hollow
      spheres.
AB  - Preparation of mesoporous Fe3O4 (magnetite) hollow spheres has been reported
      using hydrothermal synthesis and calcinations. The carboxyl-functionalized PS
      spheres were used as the templates coated by Fe3O4 particles and ethylene glycol
      (EG) as an organic structure directing agent. PS and EG were removed by
      calcinations method. The surface area after calcination at 500 degrees C is found
      to be 74 m(2) g(-1). The hollow spheres exhibited the weak ferromagnetism.

PMID- 15571700
TI  - Preparation and characterization of high-specific-surface-area activated carbons
      from K2CO3-treated waste polyurethane.
AB  - An activated carbon with high specific surface area was prepared from
      polyurethane foam by chemical activation with K2CO3 and the influences of
      carbonization temperature and impregnation ratio on the pore structure of the
      prepared activated carbon were investigated. It was found that the specific
      surface area of the activated carbon was at a maximum value (about 2800 m(2)/g)
      at a carbonization temperature of 1073 K and at an impregnation ratio of 1.0. It
      was concluded that the polyurethane foam structure was modified during
      impregnation by K2CO3, K2CO3 promoted charring during carbonization, and then the
      weight loss behavior was changed below 700 and above 1000 K, carbon in the char
      was consumed by K2CO3 reduction, and this led to the high specific surface area.
      The prepared activated carbon had a very sharp micropore size distribution,
      compared with the commercial activated carbon having high specific surface area.
      The amounts of three organic vapors (benzene, acetone, and octane) adsorbed on
      the prepared activated carbons was much larger than those on the traditional
      coconut shell AC and the same as those on the commercial activated carbon except
      for octane. We surmised that the high specific surface area was due to the
      modification of the carbonization behavior of polyurethane foam by K2CO3.

PMID- 15571701
TI  - A new form of the Cahn-Hilliard equation: applications to spinodal dewetting.
AB  - This paper presents a new form of the Cahn-Hilliard equation. The new equation is
      substantially more robust to simulating intrinsic instabilities of the spinodal
      dewetting process compared to the standard one.

PMID- 15571702
TI  - Adhesive transition from noncontacting to contacting elastic spheres: extension
      of the Maugis-Dugdale model.
AB  - In this paper, an adhesion model for spherical noncontact is proposed based on
      the Maugis-Dugdale (MD) adhesive contact model. The proposed noncontact model is
      combined with the MD contact model, thus providing a full range adhesion model
      with analytical transition from noncontacting to contacting asperity geometry.
      The proposed model is favorably compared with the full range improved DMT model
      for low surface energy values. The transition process from noncontact to contact
      and the adhesion instability that occurs during this transition are also
      investigated. It is found that jump-off points are different for displacement
      control and force control. Moreover, under displacement control, jump-on and jump
      off points are different when the adhesion parameter lambda is greater than 0.95,
      whereas they are identical for lambda<0.95. By curve fitting a relationship
      between the critical approach under displacement and force control separately and
      the adhesion parameter lambda, approach prediction equations for jump-on and jump
      off under different adhesion levels were obtained.

PMID- 15571703
TI  - Anisotropy in the wetting of rough surfaces.
AB  - Surface roughness amplifies the water-repellency of hydrophobic materials. If the
      roughness geometry is, on average, isotropic then the shape of a sessile drop is
      almost spherical and the apparent contact angle of the drop on the rough surface
      is nearly uniform along the contact line. If the roughness geometry is not
      isotropic, e.g., parallel grooves, then the apparent contact angle is no longer
      uniform along the contact line. The apparent contact angles observed
      perpendicular and parallel to the direction of the grooves are different. A
      better understanding of this problem is critical in designing rough
      superhydrophobic surfaces. The primary objective of this work is to determine the
      mechanism of anisotropic wetting and to propose a methodology to quantify the
      apparent contact angles and the drop shape. We report a theoretical and an
      experimental study of wetting of surfaces with parallel groove geometry.

PMID- 15571704
TI  - The wettability of polytetrafluoroethylene by aqueous solutions of sodium dodecyl
      sulfate and propanol mixtures.
AB  - Advancing contact-angle (theta) measurements were carried out with aqueous
      solutions of propanol and four series of aqueous solutions of dodecyl sulfate
      (SDDS) and propanol mixtures at constant dodecyl sulfate concentrations equal to
      1 x 10(-5), 6 x 10(-4), 1 x 10(-3), and 1 x 10(-2)M, respectively. The obtained
      results indicate that in the range of propanol concentrations studied there were
      considerable contact-angle changes, with exception of the solution series at a
      constant concentration value of SDDS higher than its critical micelle
      concentration. From the results of contact-angle measurements and application of
      the Gibbs and Young equations the ratio of the excess concentration of surfactant
      and propanol at the solid-aqueous solution interface to the excess of their
      concentration at the aqueous solution-air interface was calculated. From the
      calculations it appears that there is a straight linear dependence between the
      adhesion tension and surface tension of aqueous solutions of SDDS and propanol
      mixtures, and the slope of the line is equal to -1, which suggests that the
      surface excess of the SDDS and propanol mixture at the polytetrafluoroethylene
      solution interface is the same as the at the solution-air interface. The
      extrapolation of the straight line to the point corresponding to the surface
      tension of the aqueous solution, which completely spreads over the
      polytetrafluoroethylene surface, gives a critical surface tension of wetting
      equal to 23.7 mN/m. On the basis of the critical surface tension and the Young
      and modified Szyszkowski equations it was found that in a polytetrafluoroethylene
      aqueous solution of the SDDS and propanol mixture, the interface tension can be
      predicted by the modified Szyszkowski equation.

PMID- 15571705
TI  - Effect of the spacer length on the association and adsorption behavior of
      dissymmetric gemini surfactants.
AB  - A series of dissymmetric gemini surfactants with the general formula
      [C12H25(CH3)2N(CH2)sN(CH3)2C14H29]Br2 designed as 12-s-14, where s=2, 6, and 10,
      were synthesized and their physicochemical properties investigated. The effect of
      spacer length on Krafft temperature, adsorption at the air/solution interface,
      and association in aqueous solution was studied by tensiometry, conductometry,
      and cryo-transmission electron microscopy. The Krafft temperature was found to
      increase linearly with spacer length. In the submicellar concentration range the
      dissymmetric 12-s-14 surfactants display ion pairing and premicellar association.
      Adsorption at air/solution interfaces and micellization in aqueous solution are
      similar to the behavior of their symmetric counterparts and depend strongly on
      spacer length.

PMID- 15571706
TI  - Examination of the pseudophase model of monomer-micelle interconversion in
      cetylpyridinium chloride.
AB  - The 35Cl- NMR chemical shift and line width and the 1H chemical shifts of
      cetylpyridinium chloride, CPyCl, change abruptly at the critical micelle
      concentration, indicating conversion of monomeric surfactant into micelles within
      a very small range of concentration. The simple pseudophase treatment fits these
      results up to 0.05 M CPyCl, but there then appears to be a modest change in
      micellar structure. Premicelles of single chain surfactants, detected kinetically
      or photochemically, are probably formed by interactions between reactant(s) and
      surfactant.

PMID- 15571707
TI  - Effect of sol-gel transition on shear-induced drop deformation in aqueous
      mixtures of gellan and kappa-carrageenan.
AB  - In this work, we present an experimental methodology to investigate the dynamics
      under shear flow of a drop that is gelling as a consequence of a temperature
      quench. The experiments were carried out on the system water/gellan/kappa
      carrageenan in the biphasic region of the phase diagram, the gellan-rich phase
      being used as the dispersed phase. Gelation was brought about by lowering the
      temperature during flow after steady state drop deformation had been reached.
      Simple shear flow was applied by using a parallel plate apparatus equipped with
      optical microscopy and image analysis, which made it possible to monitor drop
      shape evolution before, during, and after gelation. The onset of gelation trapped
      drop deformation, thus producing anisotropic particles. The fingerprint of
      gelation was the simultaneous tumbling of the drops, which rotated as rigid
      ellipsoids under the action of shear flow. Interfacial tension between the two
      equilibrium phases was determined at different times during the temperature
      quench by analyzing drop retraction upon cessation of flow. Up to gelation, no
      significant change was observed in the measured values.

PMID- 15571708
TI  - Entropic interfaces in hard-core model amphiphilic mixtures.
AB  - We investigate bulk and interfacial properties of a recently proposed hard-body
      model for a ternary mixture of amphiphilic particles, spheres and needles using
      density functional theory. The simple model amphiphiles are formed by bonding a
      vanishingly thin needle tail radially to a hard-sphere head group. Such particles
      provide a natural amphiphile when added to a binary mixture of spheres and
      needles. As all interactions are hard, we seek to find whether amphiphilic
      effects can be driven by entropy without the need to invoke attractive
      interactions. In order to assess the amphiphilic character of the model we first
      examine the spatial and orientational distribution of the amphiphiles at the free
      interface between demixed needle-rich and amphiphile-rich fluid phases of the
      binary amphiphile-needle subsystem. We then consider the free interface between
      sphere-rich and needle-rich phases upon adding amphiphiles with low concentration
      to the demixed system. In both cases the orientational distribution of the
      particles in the interface provides strong evidence that amphiphilic properties
      can arise purely from geometrical packing effects.

PMID- 15571709
TI  - Determination of stagnant layer conductivity in polystyrene suspensions:
      temperature effects.
AB  - In the classical theory of electrokinetic phenomena, it is admitted that the
      whole electrokinetic behavior of any colloidal system is fully determined by the
      zeta potential, zeta, of the interface. However, both experimental data and
      theoretical models have shown that this is an incomplete picture, as ions in the
      stagnant layer (the region between the solid surface and the slip plane--the
      plane where the equilibrium potential equals zeta) may respond to the field. In
      this paper, we aim at the evaluation of this contribution by the estimation of
      both K(SL)(sigma) (the surface conductivity of the stagnant layer) and
      K(d)(sigma) (the conductivity associated with the diffuse layer). This will be
      done by measuring the high-frequency dielectric dispersion (HFDD) in polystyrene
      suspensions; here "high-frequency" means the frequency interval where Maxwell
      Wagner-O'Konski relaxation takes place (typically at MHz frequencies). Prior to
      any conclusions, a treatment of electrode polarization effects in the
      measurements was needed: we used two methods, and both led to similar results.
      Simulating the existence of surface conductivity by bulk conductivity, we reached
      the conclusion that no consistent explanation can be given for our HFDD and
      additional electrophoresis data based on the existence of diffuse-layer
      conductivity alone. We thus show how K(SL)(sigma) can be estimated and
      demonstrate that it can be explained by an ionic mobility very close to that
      characteristic of ions in the bulk solution. Such mobility, and hence also the
      values of K(SL)(sigma), increases with temperature as expected on simple physical
      grounds.

PMID- 15571710
TI  - Low-temperature synthesis of anatase-brookite composite nanocrystals: the
      junction effect on photocatalytic activity.
AB  - Anatase-brookite composite nanocrystals have successfully been synthesized at 50
      degrees C using a simple liquid-phase process. The photocatalytic activity of the
      sample for the gas-phase oxidation of CH3CHO is 5.4 times greater than that of a
      single-phase anatase sample with comparable crystallite size and surface area.
      Electron energy loss spectra suggest that this high activity results from
      junction between anatase and brookite crystals.

PMID- 15571711
TI  - Evolution of phonemic word fluency performance in post-stroke aphasia.
AB  - In this longitudinal study, quantitative and qualitative changes in responses of
      people with aphasia were examined on a phonemic fluency task. Eighteen patients
      were tested at 3-month intervals on the letters F-A-S while they received
      comprehensive, intensive treatment from 3 to 12 months post-stroke. They returned
      for a follow-up evaluation at an average of 10 months post-intervention. Mean
      group scores improved significantly from beginning to end of treatment, but
      declined post-intervention. Patients produced a significantly greater number and
      proportion of modifiers (adjectives and adverbs) between the beginning and end of
      treatment, with no decline afterwards, implying that they had access to a wider
      range of grammatical categories over time. Moreover, patients used significantly
      more phonemic clusters in generating word lists by the end of treatment. These
      gains may be attributed to the combined effects of time since onset and the
      linguistic and cognitive stimulation that patients received in therapy. LEARNING
      OUTCOMES: Readers of this paper should (1) gain a better understanding of verbal
      fluency performance in the assessment of aphasia, (2) recognize the importance of
      analyzing qualitative aspects of single word production in aphasia, and (3)
      contribute to their clinical judgment of long term improvement in aphasia.

PMID- 15571712
TI  - Macroglossia: a case study.
AB  - A young child with macroglossia of unknown cause was seen for treatment to modify
      resting tongue posture and improve speech sound production. Evaluation of the
      treatments indicated positive change in resting tongue posture and a modest
      change in speech sound production. Treatment for such patients can be complex and
      must consider orthodontic and/or surgical interventions, because an enlarged
      tongue can influence growth, development, and physiology of the oropharyngeal
      complex. The speech-language pathologist must be prepared to deal with the
      complex of problems demonstrated by patients with macroglossia during growth and
      development. LEARNING OUTCOMES: (1) As a result of this activity, the participant
      will be able to describe the sequelae of macroglossia. (2) As a result of this
      activity, the participant will be able to identify appropriate treatment options
      for children with macroglossia.

PMID- 15571713
TI  - Captured by details: sense-making, language and communication in autism.
AB  - The communication of people with autism spectrum disorder (ASD) is characterized
      by a qualitative impairment in verbal and non-verbal communication. In past
      decades a growing body of descriptive studies has appeared on language and
      communication problems in ASD. Reviews suggest that the development of formal and
      semantic aspects is relatively spared, whereas pragmatic skills are considered to
      be specifically impaired. This unique profile was interpreted mainly within the
      framework of the theory of mind hypothesis, which links the social-communicative
      problems of people with autism to an incapacity to attribute mental states to
      themselves and others. This approach has proven useful, but has also left many
      questions unanswered. In more recent publications, limited intentionality and
      symbol formation have been identified as core problems in ASD. Problems in symbol
      formation in particular might be better understood from the viewpoint of the
      central coherence hypothesis, which conceptualizes ASD as a weaker drive for the
      integration of information. Possible links between cognitive findings and
      communication evoke new perspectives with respect to the complex of communication
      problems in ASD. LEARNING OUTCOMES: The reader of this manuscript will be able to
      (1) describe the communication deficit in ASD; (2) discuss the central coherence
      account of ASD in relation to problems in sense-making; and (3) explain how these
      difficulties might lead to problems in communication in autism.

PMID- 15571714
TI  - Social cognition and language in children with specific language impairment
      (SLI).
AB  - This investigation examined the relationship between social pragmatics, social
      self-esteem, and language in children with specific language impairment (SLI) and
      in their age-matched peers (7-10 years). The children with SLI indicated
      significantly poorer social cognitive knowledge than their typically developing
      peers. They showed low social, but not academic self-esteem. They often used
      inappropriate negotiation and conflict resolution strategies. Their errors
      reflect some qualitative differences from those of the typically developing
      children (e.g., children with SLI use more nonverbal strategies, demonstrate
      passive/withdrawn behavior, etc.). Our data show that these children's social
      pragmatic deficit is not causally related to their language impairment; the two
      problems are co-occurring. Further, the parents and teachers of the children with
      SLI indicated different views regarding these children's social relations.
      Although the parents expressed major concerns about their children's social
      competence, the teachers did not notice this problem. LEARNING OUTCOMES: The
      reader will be able to summarize, critically analyze, and interpret the findings
      from existing research on social cognition and its relationship with language
      abilities in children with specific language impairment. Further, the reader will
      gain an understanding of the importance of applying intervention procedures that
      facilitate the use of language in different social situations, and the necessity
      of increasing parent-teacher communication in schools.

PMID- 15571715
TI  - The activity of siRNA in mammalian cells is related to the kinetics of siRNA
      target recognition in vitro: mechanistic implications.
AB  - The specificity of siRNA-mediated suppression of gene expression involves base
      base recognition between siRNA and its single-stranded RNA target. We
      investigated the kinetics of this process in vitro by using full-length ICAM-1
      target RNA and biologically active and inactive ICAM-1-directed siRNA,
      respectively. To mimic the situation in living cells we used the well
      characterised facilitator of RNA-RNA annealing and strand exchange
      cetyltrimethylammonium bromide, which increases strongly the kinetics of RNA-RNA
      interactions at conditions that do not affect RNA structure nor the presumed
      structure-function relationship. For the biologically active siRNA si2B, we find
      faster binding, i.e. recognition of the target and a slower backward reaction
      when compared with the biologically inactive siRNA si1. This is reflected by an
      approximately 400-fold more favorable equilibrium constant of si2B. Kinetic
      evidence favors an associative mechanism of recognition of the target strand by
      the double-stranded siRNA. The minimal model for siRNA-target recognition
      described here is consistent with the high biological activity of si2B only if
      one assumes a step subsequent to target recognition, which might be degradation
      of the target RNA when complexed with the antisense strand of siRNA or when
      considering rapid destruction of the released sense strand of siRNA.

PMID- 15571716
TI  - Proprotein convertase models based on the crystal structures of furin and kexin:
      explanation of their specificity.
AB  - In eukaryotes, many secreted proteins and peptide hormones are excised from
      larger precursors by calcium-dependent serine proteinases, the
      proprotein/prohormone convertases (PCs). These PCs cleave their protein
      substrates very specifically following multiple basic residues. The seven
      mammalian PCs and their yeast orthologue kexin are multi-domain proteinases
      consisting of a subtilisin-related catalytic domain, a conserved P-domain and a
      variable, often cysteine-rich domain, which in some PCs is followed by an
      additional C-terminal trans-membrane domain and a short cytoplasmic domain. The
      recently published crystal structures of the soluble mouse furin and yeast kexin
      ectodomains have revealed the relative arrangement of catalytic and P domains,
      the exact domain fold and the detailed architecture of the substrate binding
      clefts. Based on these experimental structures, we now have modelled the
      structures of the other human/mouse PCs. According to topology and to structure
      based sequence comparisons, these other PCs closely resemble furin, with PC4,
      PACE4 and PC5/6 being more similar, and PC1/3, PC2 and PC7 being less similar to
      furin. Except for PC1 and PC2, this order of similarity is valid for the
      catalytic as well as for the P domains, and is almost reversed using kexin as a
      reference molecule. A similar order results from the number and clustering of
      negative charges lining the non-prime subsites, explaining the gradually
      decreasing requirement for basic residues N-terminal to substrate cleavage sites.
      The preference of the different PCs for distinct substrates seems to be governed
      by overall charge compensation and matching of the detailed charge distribution
      pattern.

PMID- 15571717
TI  - Transcapsidation and the conserved interactions of two major structural proteins
      of a pair of phytoreoviruses confirm the mechanism of assembly of the outer
      capsid layer.
AB  - The strongly conserved amino acid sequences of the P8 outer capsid proteins of
      Rice dwarf virus (RDV) and Rice gall dwarf virus (RGDV) and the distribution of
      electrostatic potential on the proteins at the interfaces between structural
      proteins suggested the possibility that P8-trimers of RGDV might bind to the 3
      fold symmetrical axes of RDV core particles, with vertical interaction between
      heterologous P3 and P8 proteins and lateral binding of homologous P8 proteins,
      thereby allowing formation of the double-layered capsids that are characteristic
      of viruses that belong to the family Reoviridae. We proved this hypothesis using
      chimeric virus-like particles composed of the P3 core capsid protein of RDV and
      the P8 outer capsid protein of RGDV, which were co-expressed in a baculovirus
      expression system. This is the first report on the molecular biological proof of
      the mechanism of the assembly of the double-layered capsids with disparate
      icosahedral lattices.

PMID- 15571718
TI  - Identification of residues important for DNA binding in the full-length human
      Rad52 protein.
AB  - Human Rad52 (HsRad52) is a DNA-binding protein (418 residues) that promotes the
      catalysis of DNA double strand break repair by the Rad51 recombinase. HsRad52
      self-associates to form ring-shaped oligomers as well as higher order complexes
      of these rings. Analysis of the structural and functional organization of protein
      domains suggests that many of the determinants of DNA binding lie within the N
      terminal 85 residues. Crystal structures of two truncation mutants, HsRad52(1
      212) and HsRad52(1-209) support the idea that this region makes up an important
      part of the DNA binding domain. Here, we report the results of saturating alanine
      scanning mutagenesis of the N-terminal domain of full-length HsRad52 in which we
      identify residues that are likely involved in direct contact with single-stranded
      DNA (ssDNA). Our results largely agree with the position of side-chains seen in
      the crystal structures but also suggest that certain DNA binding and cross
      subunit interactions differ between the 11 subunit ring in the crystal structures
      of the truncation mutant proteins versus the seven subunit ring formed by full
      length HsRad52.

PMID- 15571719
TI  - Cooperative binding of the leucine-responsive regulatory protein (Lrp) to DNA.
AB  - The leucine-responsive regulatory protein (Lrp) of Escherichia coli activates
      expression of a number of operons and represses expression of others. For some
      members of the Lrp regulon, exogenous leucine mitigates the effect of Lrp, for
      some it potentiates the effect of Lrp, and for others it has no effect on Lrp
      action. For the ilvIH operon that we study, Lrp activates expression in vivo and
      mediates the repression of the operon by exogenous leucine. We studied Lrp-1, a
      leucine-insensitive variant, to investigate mechanisms by which leucine alters
      Lrp action as an activator of ilvIH expression. The Asp114Glu change did not have
      much effect on the amount of total Lrp-1 in cells but decreased the amount of
      free Lrp-1 two- to threefold. Lrp monomers associate to form octamers and
      hexadecamers (hexadecamer form predominates at micromolar concentrations;
      Kd=5.27x10(-8) M), and leucine promotes the dissociation of Lrp hexadecamer to a
      leucine-bound octamer. By contrast, Lrp-1 exists primarily as an octamer in
      solution (equilibrium dissociation constant 6.5x10(-5) M) and leucine had little
      effect on the equilibrium. Thus, the hexadecameric form that Lrp assumes in the
      absence of DNA is not required for activation of the ilvIH operon. Both leucine
      and the lrp-1 mutation reduced the apparent affinity of Lrp binding to ilvIH DNA
      (contains two groups of binding sites separated by 136 bp) but they have
      different effects on intrinsic binding affinity and binding cooperativity.
      Whereas leucine reduced intrinsic binding affinities and interactions of Lrps
      bound at upstream and downstream regions of ilvIH DNA, it increased cooperative
      dimer-dimer interactions of Lrps bound to two adjacent sites. By contrast, the
      lrp-1 mutation did not have much effect on intrinsic binding affinities but it
      decreased cooperative adjacent dimer-dimer interactions and enhanced interactions
      of Lrps bound at upstream and downstream regions of ilvIH DNA. Our analysis is
      consistent with the idea that leucine enhances dimer-dimer interactions that
      contribute to octamer formation, concomitantly reducing dimer-dimer interactions
      that contribute to the longer range interactions of Lrps that are required for
      activation of the ilvIH promoter.

PMID- 15571720
TI  - Specificity in protein-DNA interactions: energetic recognition by the (cytosine
      C5)-methyltransferase from HhaI.
AB  - Sequence-specific interactions between proteins and DNA are essential for a
      variety of biological functions. The (cytosine-C5)-methyltransferase from HhaI
      (M.HhaI) specifically modifies the second base in GCGC sequences, employing a
      base flipping mechanism to access the target base being chemically modified. The
      mechanism of sequence-specific recognition of M.HhaI is not evident based on
      crystallographic structures, leading to the suggestion that recognition is linked
      to the flipping event itself, a process that may be referred to as energetic
      recognition. Using computational methods, it is shown that the free energy
      barriers to flipping are significantly higher in non-cognate versus the cognate
      sequence, supporting the energetic recognition mechanism. Energetic recognition
      is imparted by two protein "selectivity filters" that function via a "web" of
      protein-DNA interactions in short-lived, high energy states present along the
      base flipping pathway. Other sequence-specific DNA binding proteins whose
      function involves significant distortion of DNA's conformation may use a similar
      recognition mechanism.

PMID- 15571721
TI  - Characterization of segments from the central region of BRCA1: an intrinsically
      disordered scaffold for multiple protein-protein and protein-DNA interactions?
AB  - The BRCA1 tumor suppressor gene encodes an 1863 amino acid gene product that is
      implicated in many cellular pathways including transcription, cell-cycle
      checkpoint control, apoptosis and DNA repair. Much attention has been focused on
      the structural and biochemical characterization of the N-terminal RING and tandem
      C-terminal BRCT domains of BRCA1. Here we used NMR spectroscopy in conjunction
      with CD spectroscopy and limited proteolysis to investigate the biophysical
      properties of the approximately 1500 residue central region of BRCA1. Our results
      show that although there are a few small, mildly protease-resistant regions, the
      majority of the BRCA1 central region lacks any pre-existing independently folded
      globular domains. Electrophoretic mobility shift assay and intrinsic tryptophan
      fluorescence experiments also demonstrate that, although intrinsically
      disordered, polypeptides from the central region are able to mediate interactions
      with DNA and p53 with affinities in the low micromolar range. This supports a
      model in which the central region may act as a long flexible scaffold for
      intermolecular interactions, thereby helping to integrate multiple signals in the
      DNA damage response pathway.

PMID- 15571722
TI  - Dimerisation of myomesin: implications for the structure of the sarcomeric M
      band.
AB  - The sarcomeric M-band is thought to provide a link between the thick and the
      elastic filament systems. So far, relatively little is known about its structural
      components and their three-dimensional organisation. Myomesin seems to be an
      essential component of the M-band, since it is expressed in all types of
      vertebrate striated muscle fibres investigated and can be found in its mature
      localisation pattern as soon as the first myofibrils are assembled. Previous work
      has shown that the N-terminal and central part of myomesin harbour binding sites
      for myosin, titin and muscle creatine kinase. Intrigued by the highly conserved
      domain layout of the C-terminal half, we screened for new interaction partners by
      yeast two-hybrid analysis. This revealed a strong interaction of myomesin with
      itself. This finding was confirmed by several biochemical assays. Our data
      suggest that myomesin can form antiparallel dimers via a binding site residing in
      its C-terminal domain 13. We suggest that, similar to alpha-actinin in the Z
      disc, the myomesin dimers cross-link the contractile filaments in the M-band. The
      new and the already previously identified myomesin interaction sites are
      integrated into the first three-dimensional model of the sarcomeric M-band on a
      molecular basis.

PMID- 15571723
TI  - Diversity and identity of mechanical properties of icosahedral viral capsids
      studied with elastic network normal mode analysis.
AB  - We analyze the mechanical properties and putative dynamical fluctuations of a
      variety of viral capsids comprising different sizes and quasi-equivalent
      symmetries by performing normal mode analysis using the elastic network model.
      The expansion of the capsid to a swollen state is studied using normal modes and
      is compared with the experimentally observed conformational change for three of
      the viruses for which experimental data exist. We show that a combination of one
      or two normal modes captures remarkably well the overall translation that
      dominates the motion between the two conformational states, and reproduces the
      overall conformational change. We observe for all of the viral capsids that the
      nature of the modes is different. In particular for the T=7 virus, HK97, for
      which the shape of the capsid changes from spherical to faceted polyhedra, two
      modes are necessary to accomplish the conformational transition. In addition, we
      extend our study to viral capsids with other T numbers, and discuss the
      similarities and differences in the features of virus capsid conformational
      dynamics. We note that the pentamers generally have higher flexibility and
      propensity to move freely from the other capsomers, which facilitates the shape
      adaptation that may be important in the viral life cycle.

PMID- 15571724
TI  - Role of C-terminal residues in oligomerization and stability of lambda CII:
      implications for lysis-lysogeny decision of the phage.
AB  - A crucial element in the lysis-lysogeny decision of the temperate coliphage
      lambda is the phage protein CII, which has several interesting properties. It
      promotes lysogeny through activation of three phage promoters p(E), p(I) and
      p(aQ), recognizing a direct repeat sequence TTGCN6TTGC at each. The three
      dimensional structure of CII, a homo-tetramer of 97 residue subunits, is unknown.
      It is an unstable protein in vivo, being rapidly degraded by the host protease
      HflB (FtsH). This instability is essential for the function of CII in the lysis
      lysogeny switch. From NMR and limited proteolysis we show that about 15 C
      terminal residues of CII are highly flexible, and may act as a target for
      proteolysis in vivo. From in vitro transcription, isothermal calorimetry and gel
      chromatography of CII (1-97) and its truncated fragments CIIA (4-81/82) and CIIB
      (4-69), we find that residues 70-81/82 are essential for (a) tetramer formation,
      (b) operator binding and (c) transcription activation. Presumably,
      tetramerization is necessary for the latter functions. Based on these results, we
      propose a model for CII structure, in which protein-protein contacts for dimer
      and tetramer formation are different. The implications of tetrameric
      organization, essential for CII activity, on the recognition of the direct repeat
      sequence is discussed.

PMID- 15571725
TI  - The first crystal structure of hyperthermostable NAD-dependent glutamate
      dehydrogenase from Pyrobaculum islandicum.
AB  - The extremely thermostable NAD-dependent glutamate dehydrogenase (NAD-GluDH) from
      Pyrobaculum islandicum, a member of the Crenarchaeota, was crystallized, and its
      3D structure has been determined by X-ray diffraction methods. The homohexameric
      structure of Pb. islandicum glutamate dehydrogenase (Pis-GluDH) was solved and
      refined at a resolution of 2.9A with a crystallographic R-factor of 19.9% (Rfree
      26.0%). The structure indicates that each subunit consists of two domains
      separated by a deep cleft containing an active site. The secondary structural
      elements and catalytically important residues of the enzyme were highly conserved
      among the NAD(P)-dependent GluDHs from other sources. A structural comparison of
      Pis-GluDH with other NAD(P)-dependent GluDHs suggests that a significant
      difference in the alpha8-loop-alpha9 region of this enzyme is associated with its
      coenzyme specificity. From the analysis of the 3D structure, hydrophobic
      interactions between intersubunits were found to be important features for the
      enzyme oligomerization. It has been reported that Pis-GluDH is highly
      thermostable, like the GluDH of the hyperthermophilic archaeum Pyrococcus
      furiosus, and the increase in the intersubunit ion pair networks is responsible
      for the extreme thermostability of the Pc. furiosus enzyme. However, the number
      of intersubunit ion pairs in the Pis-GluDH molecules is much smaller than those
      of the Pc. furiosus GluDH. The number of hydrophobic interactions at the
      intersubunit interfaces were increased and responsible for the extremely high
      thermostability. This indicates that the major molecular strategy for high
      thermostability of the GluDHs may be different for each hyperthermophile.

PMID- 15571726
TI  - Caveolin scaffolding region and cholesterol-rich domains in membranes.
AB  - A protein that constitutes a good marker for a type of cholesterol-rich domain in
      biological membranes is caveolin. A segment of this protein has a sequence that
      corresponds to a cholesterol recognition/interaction amino acid consensus (CRAC)
      motif; this motif has been suggested to cause the incorporation of proteins into
      cholesterol-rich domains. We have studied the interaction of two peptides
      containing the CRAC motif of caveolin-1 by differential scanning calorimetry,
      fluorescence, circular dichroism and magic angle spinning NMR. These peptides
      promote the segregation of cholesterol into domains from mixtures of the sterol
      with phosphatidylcholine, as shown by depletion of cholesterol from a portion of
      the membrane and enrichment of cholesterol in another domain. Cholesterol passes
      its solubility limit in the cholesterol-rich domain, resulting in the formation
      of cholesterol crystallites, suggesting that not all of the cholesterol recruited
      to this domain is bound to the peptide. NMR studies show that the peptides insert
      somewhat more deeply into membranes when cholesterol is present, but their
      strongest interaction takes place with the interfacial region of the membrane. We
      conclude that the peptides we studied containing CRAC sequences are more
      effective in promoting the formation of cholesterol-rich domains than are shorter
      peptides of this region of caveolin, which although they contain several aromatic
      amino acids, they have no CRAC motif. The presence or absence of a CRAC motif,
      however, is not a sufficient criterion to determine the extent to which a protein
      will promote the segregation of cholesterol in membranes.

PMID- 15571727
TI  - Assembly of Acanthamoeba myosin-II minifilaments. Definition of C-terminal
      residues required to form coiled-coils, dimers, and octamers.
AB  - Acanthamoeba myosin-II forms bipolar octamers by three successive steps of
      dimerization of the C-terminal, coiled-coil tail. In this study, we generated N
      terminal and C-terminal truncation constructs and point mutants of the
      Acanthamoeba myosin-II tail to delineate the structural requirements for assembly
      of bipolar mini-filaments. By the use of light-scattering, CD spectroscopy,
      analytical ultracentrifugation, and tryptophan fluorescence experiments, we
      determined that: (1) the C-terminal 14 heptad repeats plus most of the tailpiece
      (residues 1381-1509) are required to form antiparallel dimers of coiled-coils;
      (2) amino acid residues within heptads 23-32 (residues 1254-1325) are required to
      form tetramers; (3) the C-terminal 32 heptad repeats suffice to assemble
      octameric minifilaments; (4) A1378 is outside of the interaction interface; (5)
      the mutation L1475W inhibits dimerization; and (6) F1443 is involved in the
      dimerization interface but is exposed to the solvent. We propose that the
      tailpiece (residues 1483-1509) interacts with two heptads (13 and 14, residues
      1381-1393), which are important for dimerization and coiled-coil formation. These
      results support a model in which hydrophobic as well as electrostatic
      interactions control the register between myosin-II coiled-coils and guide
      sequential steps of dimerization that generate stable, octameric mini-filaments.

PMID- 15571728
TI  - Assembly of Acanthamoeba myosin-II minifilaments. Model of anti-parallel dimers
      based on EM and X-ray diffraction of 2D and 3D crystals.
AB  - Current models suggest that the first step in the assembly of Acanthamoeba myosin
      II is anti-parallel dimerization of the coiled-coil tails with an overlap of 15
      nm. Sedimentation equilibrium experiments showed that a construct containing the
      last 15 heptads and the non-helical tailpiece of the myosin-II tail (15T) forms
      dimers. To examine the structure of the 15T dimer, we grew 3D and 2D crystals
      suitable for X-ray diffraction and electron image analysis, respectively. For
      both conditions, crystals formed in related space and plane groups with similar
      unit cells (a=87.7 A, b=64.8 A, c=114.9 A, beta=108.0 degrees). Inspection of the
      X-ray diffraction pattern and molecular replacement analysis revealed the
      orientation of the coiled-coils in the unit cell. A 3D density map at 15A in
      plane resolution derived from a tilt series of electron micrographs established
      the solvent content of the 3D crystals (75%, v/v), placed the coiled-coil
      molecules at the approximate translation in the unit cell, and revealed the
      symmetry relationships between molecules. On the basis of the low-resolution 3D
      structure, biochemical constraints, and X-ray diffraction data, we propose a
      model for myosin interactions in the anti-parallel dimer of coiled-coils that
      guide the first step of myosin-II assembly.

PMID- 15571729
TI  - The N terminus of the head protein of T4 bacteriophage directs proteins to the
      GroEL chaperonin.
AB  - The head protein of T4 bacteriophage requires the GroEL chaperonin for its
      insertion into a growing T4 head. Hundreds of thousands of copies of this protein
      must pass through the chaperonin in a limited time later in infection, indicating
      that the protein must use GroEL very efficiently and may contain sequences that
      bind tightly to GroEL. We show that green fluorescent protein (GFP) fused to the
      N terminus of the head protein can fold at temperatures higher than those at
      which the GFP protein can fold well by itself. We present evidence that this
      folding is promoted by the strong binding of N-terminal head protein sequences to
      GroEL. This binding is so strong that some fusion proteins can apparently deplete
      the cell of the GroEL needed for other cellular functions, altering the cellular
      membranes and slowing growth.

PMID- 15571730
TI  - Translocation of histone proteins across lipid bilayers and Mycoplasma membranes.
AB  - We show that the three core histones H2A, H3 and H4 can transverse lipid bilayers
      of large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In
      contrast, the histone H2B, although able to bind to the liposomes, fails to
      penetrate the unilamellar and the multilamellar vesicles. Translocation across
      the lipid bilayer was determined using biotin-labeled histones and an ELISA-based
      system. Following incubation with the liposomes, external membrane-bound biotin
      molecules were neutralized by the addition of avidin. Penetrating biotin-histone
      conjugates were exposed by Triton treatment of the neutralized liposomes. The
      intraliposomal biotin-histone conjugates, in contrast to those attached only to
      the external surface, were attached to the detergent lysed lipid molecules. Thus,
      biotinylated histone molecules that were exposed only following detergent
      treatment of the liposomes were considered to be located at the inner leaflet of
      the lipid bilayers. The penetrating histone molecules failed to mediate
      translocation of BSA molecules covalently attached to them. Translocation of the
      core histones, including H2B, was also observed across mycoplasma cell membranes.
      The extent of this translocation was inversely related to the degree of membrane
      cholesterol. The addition of cholesterol also reduced the extent of histone
      penetration into the MLVs. Although able to bind biotinylated histones, human
      erythrocytes, erythrocyte ghosts and Escherichia coli cells were impermeable to
      them. Based on the present and previous data histones appear to be characterized
      by the same features that characterize cell penetrating peptides and proteins
      (CPPs).

PMID- 15571731
TI  - Trimeric structure of PRL-1 phosphatase reveals an active enzyme conformation and
      regulation mechanisms.
AB  - The PRL phosphatases, which constitute a subfamily of the protein tyrosine
      phosphatases (PTPs), are implicated in oncogenic and metastatic processes. Here,
      we report the crystal structure of human PRL-1 determined at 2.7A resolution. The
      crystal structure reveals the shallow active-site pocket with highly hydrophobic
      character. A structural comparison with the previously determined NMR structure
      of PRL-3 exhibits significant differences in the active-site region. In the PRL-1
      structure, a sulfate ion is bound to the active-site, providing stabilizing
      interactions to maintain the canonically found active conformation of PTPs,
      whereas the NMR structure exhibits an open conformation of the active-site. We
      also found that PRL-1 forms a trimer in the crystal and the trimer exists in the
      membrane fraction of cells, suggesting the possible biological regulation of PRL
      1 activity by oligomerization. The detailed structural information on the active
      enzyme conformation and regulation of PRL-1 provides the structural basis for the
      development of potential inhibitors of PRL enzymes.

PMID- 15571732
TI  - The core TatABC complex of the twin-arginine translocase in Escherichia coli:
      TatC drives assembly whereas TatA is essential for stability.
AB  - Current models for the action of the twin-arginine translocation (Tat) system
      propose that substrates bind initially to the TatBC subunits, after which a
      separate TatA complex is recruited to form an active translocon. Here, we have
      studied the roles of individual subunits in the assembly and stability of the
      core TatBC-containing substrate-binding complex. Previous studies have shown that
      TatB and TatC are active when fused together; we show here that deletion of the
      entire TatB transmembrane span from this Tat(BC) fusion inactivates the Tat
      system but does not affect assembly of the core complex. In this mutated complex,
      TatA is present but more loosely bound, indicating a role for TatB in the correct
      binding of TatA. In the absence of TatA, the truncated TatBC fusion protein still
      assembles into a complex of the correct magnitude, demonstrating that the
      transmembrane spans of TatC are the only determinants within the membrane bilayer
      that specify assembly of this complex. Further studies on both the Tat(BC)
      construct and the wild-type TatBC subunits show that the TatBC complex is
      unstable in the absence of TatA, and we show that TatA stabilises the TatB
      subunit specifically within this complex. The results demonstrate a dual role and
      location for TatA: in the functioning/maintenance of the core complex, and as a
      separate homo-oligomeric complex.

PMID- 15571733
TI  - Use of the Hermann grid illusion in the measurement of contrast perception in
      dyslexia.
AB  - We measured contrast thresholds for perception of the Hermann grid illusion,
      using different contrast polarities and mean luminances, in dyslexics and non
      dyslexics. Both groups of subjects gave significantly lower thresholds with grids
      having dark squares and light paths, but there was no significant threshold
      difference between groups. Perceived strength of illusion was also measured in
      grids at suprathreshold contrast levels. Dyslexics perceived the illusion to be
      significantly stronger than non-dyslexics when the grid had light paths and low
      luminance.

PMID- 15571734
TI  - Interocular suppression is gated by interocular feature matching.
AB  - We present a new form of contrast masking in which the target is a patch of low
      spatial frequency grating (0.46 c/deg) and the mask is a dark thin ring that
      surrounds the centre of the target patch. In matching and detection experiments
      we found little or no effect for binocular presentation of mask and test stimuli.
      But when mask and test were presented briefly (33 or 200 ms) to different eyes
      (dichoptic presentation), masking was substantial. In a 'half-binocular'
      condition the test stimulus was presented to one eye, but the mask stimulus was
      presented to both eyes with zero-disparity. This produced masking effects
      intermediate to those found in dichoptic and full-binocular conditions. We
      suggest that interocular feature matching can attenuate the potency of
      interocular suppression, but unlike in previous work (McKee, S. P., Bravo, M. J.,
      Taylor, D. G., & Legge, G. E. (1994) Stereo matching precedes dichoptic masking.
      Vision Research, 34, 1047) we do not invoke a special role for depth perception.

PMID- 15571735
TI  - Acceleration characteristics of human ocular accommodation.
AB  - Position and velocity of accommodation are known to increase with stimulus
      magnitude, however, little is known about acceleration properties. We
      investigated three acceleration properties: peak acceleration, time-to-peak
      acceleration and total duration of acceleration to step changes in defocus. Peak
      velocity and total duration of acceleration increased with response magnitude.
      Peak acceleration and time-to-peak acceleration remained independent of response
      magnitude. Independent first-order and second-order dynamic components of
      accommodation demonstrate that neural control of accommodation has an initial
      open-loop component that is independent of response magnitude and a closed-loop
      component that increases with response magnitude.

PMID- 15571736
TI  - Dynamics of perceptual bi-stability for stereoscopic slant rivalry and a
      comparison with grating, house-face, and Necker cube rivalry.
AB  - A way to study conscious perception is to expose the visual system to an
      ambiguous stimulus that instigates bi-stable perception. This provides the
      opportunity to study neural underpinnings related to the percepts rather than to
      the stimulus. We have recently developed a slant-rivalry paradigm that has
      beneficial metrical (quantitative) aspects and that exhibits temporal aspects of
      perceptual reversals that seemed to be under considerable voluntary control of
      the observer. Here we examined a range of different aspects of the temporal
      dynamics of the perceptual reversals of slant rivalry and we compared these with
      the dynamics of orthogonal grating rivalry, house-face rivalry, and Necker cube
      rivalry. We found that slant rivalry exhibits a qualitatively similar pattern of
      dynamics. The drift of the perceptual reversal rate, both across successive
      experimental repetitions, and across successive 35-s portions of data were
      similar. The sequential dependence of the durations of perceptual phases, too,
      revealed very similar patterns. The main quantitative difference, which could
      make slant rivalry a useful stimulus for future neurophysiological studies, is
      that the percept durations are relatively long compared to the other rivalry
      stimuli. In the paper that accompanies this paper [van Ee, R., van Dam, L. C. J.,
      Brouwer, G. J. (2005). Voluntary control and the dynamics of perceptual bi
      stability. Vision Research,] we focused on the role of voluntary control in the
      dynamics of perceptual reversals.

PMID- 15571737
TI  - Voluntary control and the dynamics of perceptual bi-stability.
AB  - Voluntary control and conscious perception seem to be related: when we are
      confronted with ambiguous images we are in some cases and to some extent able to
      voluntarily select a percept. However, to date voluntary control has not been
      used in neurophysiological studies on the correlates of conscious perception,
      presumably because the dynamic of perceptual reversals was not suitable. We
      exposed the visual system to four ambiguous stimuli that instigate bi-stable
      perception: slant rivalry, orthogonal grating rivalry, house-face rivalry, and
      Necker cube rivalry. In the preceding companion paper [van Ee, R. (2005).
      Dynamics of perceptual bi-stability for stereoscopic slant rivalry and a
      comparison with grating, house-face, and Necker cube rivalry. Vision Research] we
      focussed on the temporal dynamics of the perceptual reversals. Here we examined
      the role of voluntary control in the dynamics of perceptual reversals. We asked
      subjects to attempt to hold percepts and to speed-up the perceptual reversals.
      The investigations across the four stimuli revealed qualitative similarities
      concerning the influence of voluntary control on the temporal dynamics of
      perceptual reversals. We also found differences. In comparison to the other
      rivalry stimuli, slant rivalry exhibits: (1) relatively long percept durations;
      (2) a relatively clear role of voluntary control in modifying the percept
      durations. We advocate that these aspects, alongside with its metrical
      (quantitative) aspects, potentially make slant rivalry an interesting tool in
      studying the neural underpinnings of visual awareness.

PMID- 15571738
TI  - Selectivity and sparseness in the responses of striate complex cells.
AB  - Probability distributions of macaque complex cell responses to a large set of
      images were determined. Measures of selectivity were based on the overall shape
      of the response probability distribution, as quantified by either kurtosis or
      entropy. We call this non-parametric selectivity, in contrast to parametric
      selectivity, which measures tuning curve bandwidths. To examine how receptive
      field properties affected non-parametric selectivity, two models of complex cells
      were created. One was a standard Gabor energy model, and the other a slight
      variant constructed from a Gabor function and its Hilbert transform.
      Functionally, these models differed primarily in the size of their DC responses.
      The Hilbert model produced higher selectivities than the Gabor model, with the
      two models bracketing the data from above and below. Thus we see that tiny
      changes in the receptive field profiles can lead to major changes in selectivity.
      While selectivity looks at the response distribution of a single neuron across a
      set of stimuli, sparseness looks at the response distribution of a population of
      neurons to a single stimulus. In the model, we found that on average the
      sparseness of a population was equal to the selectivity of cells comprising that
      population, a property we call ergodicity. We raise the possibility that high
      sparseness is the result of distortions in the shape of response distributions
      caused by non-linear, information-losing transforms, unrelated to information
      theoretic issues of efficient coding.

PMID- 15571739
TI  - Is depth perception of stereo plaids predicted by intersection of constraints,
      vector average or second-order feature?
AB  - Stereo plaid stimuli were created to investigate whether depth perception is
      determined by an intersection of constraints (IOC) or vector average (VA)
      operation on the Fourier components, or by the second-order (non-Fourier) feature
      in a pattern. We first created stereo plaid stimuli where IOC predicted vertical
      disparity, VA predicted positive diagonal disparity and the second-order feature
      predicted negative diagonal disparity. In a depth discrimination task, observers
      indicated whether they perceived the pattern as 'near' or 'far' relative to a
      zero-disparity aperture. Observers' perception was consistent with the disparity
      predicted by VA, indicating its dominance over IOC and the second-order feature
      in this condition. Additional stimuli in which VA predicted vertical disparity
      were created to investigate whether VA would dominate perception when it was a
      less reliable cue. In this case, observers' performance was consistent with
      disparity predicted by IOC or the second-order feature, not VA. Finally, in order
      to determine whether the second-order feature contributes to depth perception,
      stimuli were created where IOC and VA predicted positive horizontal disparity
      while the second-order feature predicted negative horizontal disparity. When the
      component gratings were oriented near horizontal (+/-83 degrees from vertical),
      depth perception corresponded to that predicted by the second-order feature.
      However, as the components moved away from horizontal (+/-75 degrees and +/-65
      degrees from vertical), depth perception was increasingly likely to be predicted
      by an IOC or VA operation. These experiments suggest that the visual system does
      not rely exclusively on a single method for computing pattern disparity. Instead,
      it favours the most reliable method for a given condition.

PMID- 15571740
TI  - Differences in real and illusory shape perception revealed by backward masking.
AB  - Illusory contours (ICs) are thought to be a result of processes involved in the
      perceptual recovery of occluded surfaces. Here, we investigate the relationship
      between real and illusory contour perception using a shape discrimination task
      and backward masking paradigm. ICs can mask other ICs when times between mask
      onset and stimulus onset, or SOAs, are very long ( approximately 300 ms), but
      real contours (RCs) are not similarly effective. Masking is absent for RC masks
      at perceptually salient contrasts, as well as for those with contrast lowered to
      match the perceived brightness of the illusory surface. We also find that RCs are
      not masked at long SOAs, either by ICs or by other RCs. Finally, the masking seen
      between ICs can occur for different sizes of target and mask. The cross-size
      masking would not be expected if the masking were at a level sensitive to retinal
      contour location. The late masking therefore may be related to a higher level of
      processing of shape categories and surfaces, the level at which shapes defined by
      ICs and RCs are differentially represented.

PMID- 15571741
TI  - Dynamic competition between contour integration and contour segmentation probed
      with moving stimuli.
AB  - Line-ends, corners and junctions are important singularities for form analysis,
      object recognition, depth ordering or motion processing. In this study, we
      investigate the extent to which processing the motion of line ends depends on the
      spatial configuration of their immediate surround. To that aim, we used two
      vertical collinear line segments, translating clockwise or anti-clockwise along a
      circular path, together with a direction discrimination task. Direction
      discrimination was measured independently for outer line-ends--at both segments
      extremities--and inner line-ends--in between collinear segments--using line
      segments partially occluded by invisible masks such that the direction of either
      inner or outer line-ends' motion was restricted to a sinusoidal translation along
      a horizontal axis, and thus irrelevant for the motion task. Under these
      conditions, access to the direction of inner line-ends is longer and more
      difficult than it is for outer line-ends. Subsequent experiments show that these
      effects depend on the degree of collinearity between line segments. Similar
      experiments were performed after volunteers took a dose of Lorazepam, a
      benzodiazepine that facilitates the fixation of GABA on GABAA receptors. The
      results show that the differences between the processing of inner and outer line
      ends is reduced, suggesting that the effect of the surround is modulated by
      inhibitory mechanisms. Using a simple model, we propose that this effect can be
      explained by a competition between a segmentation process based on surround
      suppression and contour integration through long-range horizontal connections, at
      or prior to motion processing stages.

PMID- 15571742
TI  - Change in shape of the aging human crystalline lens with accommodation.
AB  - The objective was to measure the change in shape of the aging human crystalline
      eye lens in vivo during accommodation. Scheimpflug images were made of 65
      subjects between 16 and 51 years of age, who were able to accommodate at least
      1D. The Scheimpflug images were corrected for distortion due to the geometry of
      the camera and the refraction of the cornea and anterior lens surface, which is
      necessary to determine the real shape of the lens. To ensure accurate correction
      for the refraction of the anterior lens surface, the refractive index of the
      crystalline lens must be determined. Therefore, axial length was also measured,
      which made it possible to calculate the equivalent refractive index of the lens
      and possible changes in this index during accommodation. The results show that
      during accommodation there is a decrease in both the anterior and the posterior
      radius of the lens, although the change in mm per diopter of the latter is much
      smaller. The increase in lens thickness with accommodation is higher than the
      decrease in the anterior chamber depth, indicating that the posterior lens
      surface moves backwards with accommodation. During accommodation the anterior
      lens surface becomes more hyperbolic. Furthermore, an increase in the equivalent
      refractive index during accommodation was determined.

PMID- 15571743
TI  - Magnocellular reading and dyslexia.
AB  - It is pointed out that the question of the potential role of magnocellular
      neurons in reading is distinctly separate from the question of whether or not a
      magnocellular deficit is the cause of dyslexia. These two issues should not be
      confused. With regard to the second, the data do not at present favor the
      hypothesis that dyslexia is the result of a magnocellular deficit.

PMID- 15571745
TI  - Methane production and consumption in an active volcanic environment of Southern
      Italy.
AB  - Methane fluxes were measured, using closed chambers, in the Crater of Solfatara
      volcano, Campi Flegrei (Southern Italy), along eight transects covering areas of
      the crater presenting different landscape physiognomies. These included open bare
      areas, presenting high geothermal fluxes, and areas covered by vegetation, which
      developed along a gradient from the central open area outwards, in the form of
      maquis, grassland and woodland. Methane fluxes decreased logarithmically (from
      150 to -4.5 mg CH4 m(-2)day(-1)) going from the central part of the crater
      (fangaia) to the forested edges, similarly to the CO2 fluxes (from 1500 g CO2 m(
      2)day(-1) in the centre of the crater to almost zero flux in the woodlands). In
      areas characterized by high emissions, soil presented elevated temperature (up to
      70 degrees C at 0-10 cm depth) and extremely low pH (down to 1.8). Conversely, in
      woodland areas pH was higher (between 3.7 and 5.1) and soil temperature close to
      air values. Soil (0-10 cm) was sampled, in two different occasions, along the
      eight transects, and was tested for methane oxidation capacity in laboratory.
      Areas covered by vegetation mostly consumed CH4 in the following order
      woodland>macchia>grassland. Methanotrophic activity was also measured in soil
      from the open bare area. Oxidation rates were comparable to those measured in the
      plant covered areas and were significantly correlated with field CH4 emissions.
      The biological mechanism of uptake was demonstrated by the absence of activity in
      autoclaved replicates. Thus results suggest the existence of a population of
      micro-organisms adapted to this extreme environment, which are able to oxidize
      CH4 and whose activity could be stimulated and supported by elevated
      concentrations of CH4.

PMID- 15571746
TI  - Mitigating nitrous oxide and methane emissions from soil in rice-wheat system of
      the Indo-Gangetic plain with nitrification and urease inhibitors.
AB  - Mitigation of methane (CH4) and nitrous oxide (N2O) emissions from soil is
      important to reduce the global warming. Efficacy of five nitrification
      inhibitors, i.e. neem (Azadirachta melia) cake, thiosulphate, coated calcium
      carbide, neem oil coated urea and dicyandiamide (DCD) and one urease inhibitor,
      hydroquinone, in mitigating N2O and CH4 emissions from fertilized soil was tested
      in rice-wheat system in the Indo-Gangetic plains. The closed chamber technique
      was used for the collection of gas samples, which were analyzed using gas
      chromatography. Reduction in N2O emission on the application of
      nitrification/urease inhibitors along with urea ranged from 5% with hydroquinone
      to 31% with thiosulphate in rice and 7% with hydroquinone to 29% with DCD in
      wheat crop. The inhibitors also influenced the emission of CH4. While application
      of neem coated urea, coated calcium carbide, neem oil and DCD reduced the
      emission of CH4; hydroquinone and thiosulphate increased the emission when
      compared to urea alone. However, the global warming potential was lower with the
      inhibitors (except hydroquinone) as compared to urea alone, suggesting that these
      substances could be used for mitigating greenhouse gas emission from the rice
      wheat systems.

PMID- 15571747
TI  - DMS photochemistry during the Asian dust-storm period in the Spring of 2001:
      model simulations vs. field observations.
AB  - This study examines the local/regional DMS oxidation chemistry on Jeju Island
      (33.17 degrees N, 126.10 degrees E) during the Asian dust-storm (ADS) period of
      April 2001. Three ADS events were observed during the periods of April 10-12, 13
      14, and 25-26, respectively. For comparative purposes, a non-Asian-dust-storm
      (NADS) period was also considered in this study, which represents the entire
      measurement periods in April except the ADS events. The atmospheric
      concentrations of DMS and SO2 were measured at a ground station on Jeju Island,
      Korea, as part of the ACE-Asia intensive operation. DMS (means of 34-52 pptv) and
      SO2 (means of 0.96-1.14 ppbv) levels measured during the ADS period were higher
      than those (mean of 0.45 ppbv) during the NADS period. The enhanced DMS levels
      during the ADS period were likely due to the increase in DMS flux under reduced
      oxidant levels (OH and NO3). SO2 levels between the two contrasting periods were
      affected sensitively by some factors such as air mass origins. The diurnal
      variation patterns of DMS observed during the two periods were largely different
      from those seen in the background environment (e.g., the marine boundary layer
      (MBL)). In contrast to the MBL, the maximum DMS value during the ADS period was
      seen in the late afternoon at about sunset; this reversed pattern appears to be
      regulated by certain factors (e.g., enhanced NO3 oxidation). The sea-to-air
      fluxes of DMS between the ADS and NADS periods were calculated based on the mass
      balance photochemical-modeling approach; their results were clearly distinguished
      with the values of 4.4 and 2.4 micromole m(-2) day(-1), respectively. This study
      confirmed that the contribution of DMS oxidation to observed SO2 levels on Jeju
      Island was not significant during our study period regardless of ADS or NADS
      periods.

PMID- 15571748
TI  - Global sulfur emissions from 1850 to 2000.
AB  - The ASL database provides continuous time-series of sulfur emissions for most
      countries in the World from 1850 to 1990, but academic and official estimates for
      the 1990s either do not cover all years or countries. This paper develops
      continuous time series of sulfur emissions by country for the period 1850-2000
      with a particular focus on developments in the 1990s. Global estimates for 1996
      2000 are the first that are based on actual observed data. Raw estimates are
      obtained in two ways. For countries and years with existing published data I
      compile and integrate that data. Previously published data covers the majority of
      emissions and almost all countries have published emissions for at least 1995.
      For the remaining countries and for missing years for countries with some
      published data, I interpolate or extrapolate estimates using either an
      econometric emissions frontier model, an environmental Kuznets curve model, or a
      simple extrapolation, depending on the availability of data. Finally, I discuss
      the main movements in global and regional emissions in the 1990s and earlier
      decades and compare the results to other studies. Global emissions peaked in 1989
      and declined rapidly thereafter. The locus of emissions shifted towards East and
      South Asia, but even this region peaked in 1996. My estimates for the 1990s show
      a much more rapid decline than other global studies, reflecting the view that
      technological progress in reducing sulfur based pollution has been rapid and is
      beginning to diffuse worldwide.

PMID- 15571749
TI  - Photochemical production of methane in natural waters: implications for its
      present and past oceanic source.
AB  - We conducted irradiation experiments with riverine, estuarine, and marine water
      samples to investigate the possibility of photochemical methane (CH4) formation.
      CH4 photoproduction was undetectable under oxic conditions or in the absence of
      methyl radical precursors indicating that its photochemical formation is
      negligible in the present ocean. Significant photochemical CH4 production was
      observed in the presence of a methyl radical precursor such as acetone under
      strictly anoxic conditions. Our results indicate an indirect formation mechanism
      with coloured dissolved organic matter acting as photosensitizer. We suggest that
      photochemical CH4 formation might have occurred in the anoxic ocean surface layer
      of the Archean prior to the onset of O2 accumulation in the atmosphere at around
      2300 million years ago. Oceanic CH4 photoproduction via methyl radical (CH3)
      precursors and its subsequent release to the atmosphere may have contributed to
      high CH4 mixing ratios in the Archean atmosphere.

PMID- 15571750
TI  - Effects of copper concentration on methane emission from rice soils.
AB  - Outdoor pot experiments with various paddy soils representing five soil types
      were conducted at Nanjing Agricultural University during the 2000 and 2001 rice
      growing seasons. Eighteen soils and ten out of the eighteen soils were involved
      in the 2000 and the 2001 experiment, respectively. Two treatments were designed
      as mineral fertilization (MF) and mineral fertilizer + wheat straw incorporation
      (MF + WS) for the 2001 experiment. Seasonal average rate of CH4 emission from
      different soils ranged from 1.96 to 11.06 mg m(-2) h(-1) in the 2000 experiment,
      and from 0.89 to 5.92 mg m(-2) h(-1) for the MF treatment in the 2001 experiment,
      respectively. Incorporation of wheat straw enhanced considerably CH4 emission
      with an average increment of 7.09 mg m(-2) h(-1). CH4 emissions from the two-year
      experiment were negatively correlated to soil available and total copper
      concentration. A further investigation showed that CH4 emission from the MF
      treatment was positively related to the dissolved organic carbon (DOC) in the
      soil (r = 0.904, p < 0.001), and that the DOC was negatively correlated to the
      concentrations of available copper (r = -0.844, p < 0.01) and total copper (r = 
      0.833, p < 0.01), respectively. Nevertheless, the incorporation of wheat straw
      did not enhance the soil DOC, and the relationship between CH4 emission and soil
      DOC was not statistically significant (r = 0.470, p < 0.20). It was concluded
      that higher concentration of copper in the soils resulted in lower soil DOC and
      thus reduced CH4 emission when there was no additional organic matter input.
      Incorporation of wheat straw did not affect soil DOC and available copper
      concentration but enhanced CH4 emission.

PMID- 15571751
TI  - Dissolution and solubility of trace metals from natural and anthropogenic aerosol
      particulate matter.
AB  - An open flow reactor is used to simulate the dissolution process of mineral
      aerosol particles in atmospheric water droplets. Data on dissolution kinetic and
      solubility are provided for the major trace metals from two kinds of matrix:
      alumino-silicated and carbonaceous sample. The results emphasise that the metals
      contained in the carbonaceous aerosols are easier dissolved than in the alumino
      silicated particles. The released concentrations are not related to the total
      metal composition or the origin of particles, but are directly associated with
      the type of liaisons whereby the metals are bound in the solid matrix. Thus, the
      metals coming from carbonaceous particles are adsorbed impurities or salts and
      hence are very soluble and with a dissolution hardly dependent on pH, whereas the
      metals dissolved from alumino-silicated particles are less soluble, notably the
      ones constitutive of the matrix network (Fe, Mn), and with a dissolution highly
      influenced by pH. Consequently, in the regions with an anthropogenic influence,
      the dissolved concentrations of metals found in the atmospheric waters are mainly
      governed by the elemental carbon content. Moreover, it appears that the
      dissolution kinetic of metals is not constant as a function of time. The
      dissolution rates are very rapid in the first 20 min of leaching and then they
      are stabilised to lower values in comparison to initial rates. By consequence,
      the total dissolved metal content is provided after the first 20 min of the
      droplet lifetime. For this reason, the effects of trace metals on the atmospheric
      aqueous chemistry and as atmospheric wet input to the marine biota are maximal
      for "aged" droplets.

PMID- 15571752
TI  - Effects of environmental factors on N2O emission from and CH4 uptake by the
      typical grasslands in the Inner Mongolia.
AB  - The fluxes of N2O emission from and CH4 uptake by the typical semi-arid
      grasslands in the Inner Mongolia, China were measured in 1998-1999. Three
      steppes, i.e. the ungrazed Leymus chinensis (LC), the moderately grazed Leymus
      chinensis (LC) and the ungrazed Stipa grandis (SG), were investigated, at a
      measurement frequency of once per week in the growing seasons and once per month
      in the non-growing seasons of the LC steppes. In addition, four diurnal-cycles of
      the growing seasons of the LC steppes, each in an individual stage of grass
      growth, were measured. The investigated steppes play a role of source for the
      atmospheric N2O and sink for the atmospheric CH4, with a N2O emission flux of
      0.06-0.21 kg N ha(-1) yr(-1) and a CH4 uptake flux of 1.8-2.3 kg C ha(-1) yr(-1).
      Soil moisture primarily and positively regulates the spatial and seasonal
      variability of N2O emission. The usual difference in soil moisture among various
      semi-arid steppes does not lead to significantly different CH4 uptake
      intensities. Soil moisture, however, negatively regulates the seasonal
      variability in CH4 uptake. Soil temperature of the most top layer might be the
      primary driving factor for CH4 uptake when soil moisture is relatively low. The
      annual net emission of N2O and CH4 from the ungrazed LC steppe, the moderately
      grazed LC steppe and the ungrazed SG steppe is at a CO2 equivalent rate of 7.7,
      0.8 and -7.5 kg CO2-C ha(-1) yr(-1), respectively, which is at an ignorable
      level. This implies that the role of the semi-arid grasslands in the atmospheric
      greenhouse effect in terms of net emission of greenhouse gases (CO2, CH4 and N2O)
      may exclusively depend upon the net exchange of net ecosystem CO2 exchange.

PMID- 15571753
TI  - Shortwave radiative forcing efficiency of urban aerosols--a case study using
      ground based measurements.
AB  - Aerosols reduce the surface reaching solar flux by scattering the incoming solar
      radiation out to space. Various model studies on climate change suggest that
      surface cooling induced by aerosol scattering is the largest source of
      uncertainty in predicting the future climate. In the present study measurements
      of aerosol optical depth (AOD) and its direct radiative forcing efficiency has
      been presented over a typical tropical urban environment namely Hyderabad during
      December, 2003. Measurements of AOD have been carried out using MICROTOPS-II
      sunphotometer, black carbon aerosol mass concentration using Aethalometer, total
      aerosol mass concentration using channel Quartz Crystal Microbalance (QCM)
      Impactor Particle analyser and direct normal solar irradiance using Multifilter
      Rotating Shadow Band Radiometer (MFRSR). Diurnal variation of AOD showed high
      values during afternoon hours. The fraction of BC estimated to be approximately
      9% in the total aerosol mass concentration over the study area. Results of the
      study suggest -62.5 Wm(-2) reduction in the ground reaching shortwave flux for
      every 0.1 increase in aerosol optical depth. The results have been discussed in
      the paper.

PMID- 15571754
TI  - A pilot study of methyl chloride emissions from tropical woodrot fungi.
AB  - Flux chamber measurements made in a rainforest provide evidence that methyl
      chloride is emitted from rotting wood. However, its net flux was found to be into
      the soil, probably due to competing production and consumption processes within
      the soil. Evidence was found for a regional source, possibly vegetation, since
      its concentration above the canopy was substantially greater than reported
      average equatorial values.

PMID- 15571755
TI  - Cortisol pulsatility and its role in stress regulation and health.
AB  - One of the classic characteristics of the human stress response is the wide inter
      individual variation. Although there is much current interest in the genetic and
      environmental contributions to these differences, studies on human subject have
      been sparse and characterised by methodological problems. The major factor that
      is rarely taken into account is the intrinsic rhythmicity of hypothalamo
      pituitary-adrenal activity, not simply the classic diurnal variation but also the
      endogenous pulsatility which is similar to, but much less well recognized than,
      the rhythms found within the reproductive and growth hormone axes. In this review
      we propose some novel ideas relating to the importance of pulsatility both for
      the design of human stress-response studies and for their interpretation as well
      as implications for our understanding of disease.

PMID- 15571756
TI  - Physiology of BDNF: focus on hypothalamic function.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family which
      interacts with high-affinity protein kinase receptors (Trk) and the unselective
      p75(NGFR) receptor. The BDNF gene has a complex structure with multiple
      regulatory elements and four promoters that are differentially expressed in
      central or peripheral tissue. BDNF expression is regulated by neuronal activity
      or peripheral hormones. Neurotrophins regulate the survival and differentiation
      of neurons during development but growing evidence indicates that they are also
      involved in several functions in adulthood, including plasticity processes. BDNF
      expression in the central nervous system (CNS) is modified by various kinds of
      brain insult (stress, ischemia, seizure activity, hypoglycemia, etc.) and
      alterations in its expression may contribute to some pathologies such as
      depression, epilepsy, Alzheimer's, and Parkinson's disease. Apart from very
      traumatic situations, the brain functioning is resilient to stress and capable of
      adaptive plasticity. Neurotrophins might act as plasticity mediators enhancing
      this trait which seems to be crucial in adaptive processes. In addition to
      documenting all of the topics mentioned above in the CNS, we review the state of
      the art concerning neurotrophins and their receptors, including our personal
      contribution which is essentially focused on the stress response.

PMID- 15571757
TI  - Ontogeny of GnRH and olfactory neuronal systems in man: novel insights from the
      investigation of inherited forms of Kallmann's syndrome.
AB  - GnRH embryonic neuronal fate is determined by discreet spatio-temporal expression
      patterns and interactions of axonal guidance and cell adhesion molecules and
      extracellular matrix proteins. Expression of several transcription factors,
      locally derived growth factors and neurotransmitters influence GnRH ontogeny and
      rostral forebrain specification. In man, disrupted GnRH neuronal ontogeny can be
      caused by several monogenic disorders leading to isolated hypogonadotrophic
      hypogonadism (IHH); these include mutations within KAL-1, GnRH-R, and FGFR1.
      Mutations in KAL-1 and its encoded protein anosmin-1, causes X-linked Kallmann's
      syndrome (XKS) characterized by IHH, anosmia, synkinesis, and unilateral renal
      agenesis. Anosmin-1 has an obligate functional interaction with membrane
      associated heparan sulphate proteoglycans (HSPG) and FGFR-1 (KAL-2) whose
      mutations lead to the autosomal dominant form of KS (AKS). FGFR1 and anosmin-1
      may interact via a HSPG dependent mechanism raising the possibility of
      interaction between two single gene defects cause similar phenotypic
      abnormalities.

PMID- 15571759
TI  - Release of patients after therapy with unsealed radionuclides.
AB  - After some therapeutic nuclear medicine procedures with unsealed radionuclides,
      precautions may be needed to limit doses to other people, but this is rarely the
      case after diagnostic procedures. Iodine-131 results in the largest dose to
      medical staff, the public caregivers, and relatives. Other radionuclides used in
      therapy are usually simple beta emitters (e.g. phosphorus-32, strontium-89, and
      yttrium-90) that pose much less risk. Dose limits apply to exposure of the public
      and medical staff from patients. Previously, the ICRP has recommended that a
      source-related dose constraint for optimisation of a few mSv/episode applies to
      relatives, visitors, and caregivers at home, rather than a dose limit. The
      present report recommends that young children and infants, as well as visitors
      not engaged in direct care or comforting, should be treated a s members of the
      public (i.e. be subject to the public dose limit.) The modes of exposure to other
      people are: external exposure; internal exposure due to contamination; and
      environmental pathways. Dose to adults from patients is mainly due to external
      exposure. Contamination of infants and children with saliva from a patient could
      result in significant doses to the child's thyroid. It is important to avoid
      contamination of children and pregnant women. After radioiodine therapy, mothers
      must cease breastfeeding immediately. Many types of therapy with unsealed
      radionuclides are contraindicated in pregnant females. Women should not become
      pregnant for some time after radioisotope therapy. Technetium-99m dominates
      discharges to the environment from excreta of nuclear medicine patients, but its
      short half-life limits its importance. The second largest discharges, iodine-131,
      can be detected in the environment after medical uses but with no measurable
      environmental impact. Storing patient's urine after therapy appears to have
      minimal benefit. Radionuclides released into modern sewage systems are likely to
      result in doses to sewer workers and the public that are well below public dose
      limits. The decision to hospitalise or release a patient should be determined on
      an individual basis. In addition to residual activity in the patient, the
      decision should take many other factors into account. Hospitalisation often
      involves a significant psychological burden as well as monetary and other costs
      that should be analysed and justified. Patients travelling after radioiodine
      therapy rarely present a hazard to other passengers if travel times are limited
      to a few hours. Environmental or other radiation-detection devices are able to
      detect patients who have had radioiodine therapy for several weeks after
      treatment. Personnel operating such detectors should be specifically trained to
      identify and deal with nuclear medicine patients. Records of the specifics of
      therapy with unsealed radionuclides should be maintained at the hospital and
      given to the patient along with written precautionary instructions. In the case
      of death of a patient who has had radiotherapy with unsealed radionuclides in the
      last few months, special precautions may be required.

PMID- 15571761
TI  - Lifting new drugs from old books.

PMID- 15571762
TI  - Leibniz's women.
AB  - Enlightenment natural philosophers were linked to one another in an extended
      correspondence network, but the female participants in this international
      Republic of Letters are rarely mentioned. Gottfried Leibniz relied on several
      such women not only for financial patronage, but also for intellectual
      stimulation. Although this hardworking and underpaid librarian at the Hanoverian
      Court is now one of the world's most famous mathematical philosophers, the women
      on whom he depended for ideas as well as support have been largely forgotten.

PMID- 15571763
TI  - Balloon mania: news in the air.
AB  - The hot-air balloon, invented by the Montgolfier brothers in 1783, enabled the
      French King to project his glory, the nobility to exhibit their valor, the
      literary public to transmit the ideal of the Enlightenment and the plebian public
      to rejoice in a scientific spectacle. The ensuing balloon mania helped create an
      integrated public that, because of its size and composition, can only be
      described as 'democratic' just a few years before the French Revolution. The
      monumental impact of the balloon was well represented in a flood of poetry,
      pamphlets, books, journal reports, academic papers and consumer items. Sifting
      through these artifacts and considering the crowd that witnessed the ascent of
      the balloon will bring us to the historical moment when things, spectacles, and
      events (rather than words) shaped public and popular opinion.

PMID- 15571764
TI  - The exotic world of Pierre Pomet's A Compleat History of Druggs.
AB  - The English translation of Pierre Pomet's A Compleat History of Druggs (1712)
      demonstrates how the expansion of print culture altered the way that scientific
      ideas were communicated. Although it makes utilitarian claims, the text of the
      History departs from the style of contemporary British pharmacopoeias by
      emphasizing the exotic aspects of drugs. In this sense, the text exemplifies how
      Enlightenment science could be sold to a cross-over audience interested as much
      in the fantastical as in the quality and operation of drugs.

PMID- 15571765
TI  - The tail end of the moth: clarifying species boundaries.
AB  - The search by naturalists for good characters upon which to base both
      classifications and determinations of species led some 19th century entomologists
      to put their faith in insect genitalia as a criteria by which they could
      differentiate between and classify forms. Karl Jordan was such an entomologist,
      who turned to these tiny structures as an aid to his work as a museum curator to
      identify, describe and classify moths and butterflies. In his writings on the
      subject he also demonstrated how the attempts of systematists to order the
      diversity of nature had profound implications for the efforts of biologists to
      explain the origin of that diversity. However, Jordan's plan of how to do
      systematics well required much more than convincing biologists of the importance
      of museum work. It also depended on refining the priorities of a natural history
      community that worked according to diverse means, priorities and methods during a
      tumultuous century.

PMID- 15571766
TI  - The making of scientific butter: injecting scientific reasoning into agriculture.
AB  - Both Danish and English agriculture underwent fundamental restructuring during
      the second half of the 19th century, and in both cases the dairy sector made
      great advances. However, the two agricultural industries differed in aims and
      strategies, and crucially in the extent to which new technologies and scientific
      methods were implemented. Economic historical analysis is insufficient to explain
      why the Danish and English dairy industries developed in different ways, and how
      Danish butter achieved success in the competitive English market. However, with a
      focus on the role of science and a scientific understanding of the development of
      these two dairy industries, all becomes clear.

PMID- 15571767
TI  - The Nazi symbiosis: politics and human genetics at the Kaiser Wilhelm Institute.
AB  - The case of the Kaiser Wilhelm Institute for Anthropology, Human Heredity and
      Eugenics (KWIA), from its inception in Weimar Republic Germany to its apogee
      under the rule of the Third Reich, is an example of how politics and human
      heredity can function as mutually beneficial resources. Whether it was a result
      of the Nazi bureaucrats' desire to legitimize their racial policy through
      science, or the KWIA personnel's desire to secure more funding for their
      research, the symbiotic relationship that developed between human genetics and
      Nazi politics could help explain why many scientists in the Third Reich undertook
      research projects that wholly transgressed the boundaries of morally acceptable
      science.

PMID- 15571768
TI  - Physiology of cerebral venous blood flow: from experimental data in animals to
      normal function in humans.
AB  - In contrast to the cerebroarterial system, the cerebrovenous system is not well
      examined and only partly understood. The cerebrovenous system represents a
      complex three-dimensional structure that is often asymmetric and considerably
      represent more variable pattern than the arterial anatomy. Particular emphasis is
      devoted to the venous return to extracranial drainage routes. As the state-of-the
      art-imaging methods are playing a greater role in visualizing the intracranial
      venous system at present, its clinically pertinent anatomy and physiology has
      gain increasing interest, even so only few data are available. For this reason,
      experimental research on specific biophysical (fluid dynamic, rheologic factors)
      and hemodynamic (venous pressure, cerebral venous blood flow) parameters of the
      cerebral venous system is more on the focus; especially as these parameters are
      different to the cerebral arterial system. Particular emphasis is devoted to the
      venous return to extracranial drainage routes. From the present point of view, it
      seems that the cerebrovenous system may be one of the most important factors that
      guarantee normal brain function. In the light of this increasing interest in the
      cerebral venous system, the authors have summarized the current knowledge of the
      physiology of the cerebrovenous system and discuss it is in the light of its
      clinical relevance.

PMID- 15571769
TI  - Brain microglia and blood-derived macrophages: molecular profiles and functional
      roles in multiple sclerosis and animal models of autoimmune demyelinating
      disease.
AB  - Microglia and macrophages, one a brain-resident, the other a mostly hematogenous
      cell type, represent two related cell types involved in the brain pathology in
      multiple sclerosis and its autoimmune animal model, the experimental allergic
      encephalomyelitis. Together, they perform a variety of different functions: they
      are the primary sensors of brain pathology, they are rapidly recruited to sites
      of infection, trauma or autoimmune inflammation in experimental allergic
      encephalomyelitis and multiple sclerosis and they are competent presenters of
      antigen and interact with T cells recruited to the inflamed CNS. They also
      synthesise a variety of molecules, such as cytokines (TNF, interleukins),
      chemokines, accessory molecules (B7, CD40), complement, cell adhesion
      glycoproteins (integrins, selectins), reactive oxygen radicals and neurotrophins,
      that could exert a damaging or a protective effect on adjacent axons, myelin and
      oligodendrocytes. The current review will give a detailed summary on their
      cellular response, describe the different classes of molecules expressed and
      their attribution to the blood derived or brain-resident macrophages and then
      discuss how these molecules contribute to the neuropathology. Recent advances
      using chimaeric and genetically modified mice have been particularly telling
      about the specific, overlapping and nonoverlapping roles of macrophages and
      microglia in the demyelinating disease. Interestingly, they point to a crucial
      role of hematogenous macrophages in initiating inflammation and myelin removal,
      and that of microglia in checking excessive response and in the induction and
      maintenance of remission.

PMID- 15571770
TI  - Targeting mitochondrial ATP-sensitive potassium channels--a novel approach to
      neuroprotection.
AB  - Mitochondrial responses to ischemic stress play an important role in necrosis and
      apoptosis of brain cells. Recent studies using several different experimental
      preparations have shown that activation of ATP-sensitive potassium channels in
      mitochondria (mitoK(ATP) channels) is able to protect neurons and astroglia
      against injury and death. Thus, targeting of mitoK(ATP) channels appears to be a
      novel approach to neuroprotection. However, little is known about the mechanisms
      involved. The purpose of this review is to detail the current state of knowledge
      about this important, emerging area of investigation, and to provide suggestions
      for future studies.

PMID- 15571771
TI  - Descending control of persistent pain: inhibitory or facilitatory?
AB  - The periaqueductal gray matter (PAG) and the nucleus raphe magnus and adjacent
      structures of the rostral ventromedial medulla (RVM), with their projections to
      the spinal dorsal horn, constitute the "efferent channel" of a pain-control
      system that "descends" from the brain onto the spinal cord. Considerable evidence
      has recently emerged regarding participation of this system in persistent pain
      conditions such as inflammation and neuropathy. Herein, this evidence is reviewed
      and organized to support the idea that persistent nociception simultaneously
      triggers descending facilitation and inhibition. In models of inflammation,
      descending inhibition predominates over facilitation in pain circuits with input
      from the inflamed tissue, and thus attenuates primary hyperalgesia, while
      descending facilitation predominates over inhibition in pain circuits with input
      from neighboring tissues, and thus facilitates secondary hyperalgesia. Both
      descending facilitation and inhibition mainly stem from RVM. The formalin-induced
      primary hyperalgesia, although considered a model for inflammation, is mainly
      facilitated from RVM. Also, formalin-induced secondary hyperalgesia is
      facilitated by RVM. Again, formalin triggers a concomitant but concealed
      descending inhibition. The (primary) hyperalgesia and allodynia of the
      neuropathic syndrome are also facilitated from RVM. Simultaneously, there is an
      inhibition of secondary neuronal pools that is partly supported from the PAG.
      Because in all these models of peripheral damage descending facilitation and
      inhibition are triggered simultaneously, it will be important to elucidate why
      inhibition predominates in some neuronal pools and facilitation in others.
      Therapies that enhance descending inhibition and/or attenuate descending
      facilitation are furthermore an important target for research in the future.

PMID- 15571772
TI  - The Project for a Scientific Psychology (1895): a Freudian anticipation of LTP
      memory connection theory.
AB  - Long-term potentiation (LTP) of synaptic transmission is considered a reliable
      cellular model of several forms of learning and memory. Described for the first
      time in 1973, this synaptic phenomenon consists in the enduring facilitation of
      the communication between two neurons in response to the sustained activation of
      the synapses by which they are interconnected. In a book of 1895 entitled Project
      for a Scientific Psychology, Sigmund Freud theorized about the possibility of
      representing memory at the synaptic level as "a permanent alteration following an
      event", and anticipated several crucial physiological properties of LTP. In the
      present article we aim at presenting Freudian theory on the functional
      organization of the nervous system developed in the Project, with particular
      respect to his ideas of the cellular bases of memory.

PMID- 15571773
TI  - Investigating the cortical origins of motor overflow.
AB  - Motor overflow refers to the involuntary movements which may accompany the
      production of voluntary movements. While overflow is not usually seen in the
      normal population, it does present in children and the elderly, as well as those
      suffering certain neurological dysfunctions. Advancements in methodology over the
      last decade have allowed for more convincing conclusions regarding the cortical
      origins of motor overflow. However, despite significant research, the exact
      mechanism underlying the production of motor overflow is still unclear. This
      review presents a more comprehensive conceptualization of the theories of motor
      overflow, which have often been only vaguely defined. Further, the major findings
      are explored in an attempt to differentiate the competing theories of motor
      overflow production. This exploration is done in the context of a range of
      neurological and psychiatric disorders, in order to elucidate the possible
      underlying mechanisms of overflow.

PMID- 15571774
TI  - Sphingolipid metabolites in neural signalling and function.
AB  - Sphingolipid metabolites, such as ceramide, sphingosine, sphingosine-1-phosphate
      (S1P) and complex sphingolipids (gangliosides), are recognized as molecules
      capable of regulating a variety of cellular processes. The role of sphingolipid
      metabolites has been studied mainly in non-neuronal tissues. These studies have
      underscored their importance as signals transducers, involved in control of
      proliferation, survival, differentiation and apoptosis. In this review, we will
      focus on studies performed over the last years in the nervous system, discussing
      the recent developments and the current perspectives in sphingolipid metabolism
      and functions.

PMID- 15571775
TI  - Exploring permeability of Escherichia coli competence using quantum dots as
      fluorescent probes.
AB  - Though people had recognized the pivotal function of CaCl(2) during DNA
      transformation into Escherichia coli, the mechanism of divalent Ca(2+) cation
      inducing E. coli competence development is still unknowable. Quantum dots (QDs),
      as a new fluorescent probe, being applied in biology research, had aroused great
      interest. We explored the penetrability of E. coli competent cells membrane using
      QDs and proved directly that competent cells were more permeable than that of
      noncompetent. The results are significant on understanding the problems of the
      microbiological genetics.

PMID- 15571776
TI  - The evaluation of the oxidative state of native-LDL: three methods compared.
AB  - LDL-oxidation is considered a contributing factor to the development of
      atherosclerotic lesions. However, to utilise the oxidative state of LDL as a
      marker of cardiovascular risk, reliable analytical methods for its detection must
      be defined. We have compared three methods for their capacity to evaluate the
      difference in the oxidation state of isolated LDL subjected to either dialysis (D
      LDL) or gel filtration (F-LDL) to remove EDTA. Their susceptibility to oxidation
      promoted by Cu(2+) was monitored by following the time course of conjugated diene
      (CD) and lipid hydroperoxide (ROOH) accumulation. The relative electrophoretic
      mobility (REM) of the same LDL samples was evaluated by capillary
      electrophoresis. As measured by all three methods, F-LDL are less prone to
      oxidation than D-LDL when added with CuSO(4). REM of F-LDL and D-LDL
      significantly differs already before the addition of the metal catalyst, whereas
      CD and ROOH contents become significantly different only after it. Besides
      confirming that a rapid centrifugation followed by gel filtration is a more
      convenient procedure than dialysis to remove EDTA during LDL isolation, our study
      suggests the REM of isolated-LDL as the biochemical marker of choice in the
      evaluation of its oxidative state.

PMID- 15571777
TI  - Real-Time, label-free monitoring of tumor antigen and serum antibody
      interactions.
AB  - Conventional techniques for the detection of biomolecular interactions can be
      limited by the need for exogenous labels, time- and labor-intensive protocols, as
      well as by poor sensitivity levels. A refractometer instrument has been
      reconfigured to detect biomolecular interactions through changes in surface
      plasmon resonance (SPR). The binding kinetics and affinity values of anti-NY-ESO
      1 monoclonal antibody, ES121, to the cancer-testis antigen NY-ESO-1 were
      determined according to the surface heterogeneity model and resulted in K(D)
      values of 1.3x10(-9) and 2.1x10(-10) M. The reconfigured instrument was then used
      to measure the interaction between tumor antigens and serum antibodies against
      these antigens in preselected cancer patient sera samples. The tumor antigens
      assayed included NY-ESO-1, SSX2 and p53, all used as recombinant proteins
      containing polyhistidine tags. These results demonstrated that the instrument is
      capable of detecting the binding of serum antibodies from cancer patient sera to
      immobilized tumor antigens, consistent with those observed previously in ELISA
      based experiments. These results demonstrate the potential of SPR technology for
      the rapid diagnosis and monitoring immune responses.

PMID- 15571778
TI  - Novel potentiometry immunoassay with amplified sensitivity for diphtheria antigen
      based on Nafion, colloidal Ag and polyvinyl butyral as matrixes.
AB  - A novel potentiometry immunoassay with amplified sensitivity has been developed
      for the detection of diphtheria antigen (Diph) via immobilizing diphtheria
      antibody (anti-Diph) on a platinum electrode based on Nafion, colloidal Ag (Ag),
      and polyvinyl butyral (PVB) as matrixes in this study. The modified procedure was
      further characterized by electrochemical impedance spectroscopy (EIS) and cyclic
      voltammetry (CV). The influence and factors influencing the performance of
      resulting immunosensor were studied in detail. The resulting immunosensor
      exhibited sigmoid curve with log Diph concentrations, high sensitivity (51.4
      mV/decade), wide linear range from 8 to 800 ng ml(-1) with a detection limit of
      1.5 ng ml(-1), rapid potentiometric response (<3 min) and long-term stability (>6
      months). Analytical results of clinical samples show that the developed
      immunoassay is comparable with the enzyme-linked immunosorbent assays (ELISAs)
      method, implying a promising alternative approach for detecting diphtheria
      antigen in the clinical diagnosis.

PMID- 15571779
TI  - A sensitive and specific HPLC method for the determination of total pentosidine
      concentration in plasma.
AB  - Pentosidine is an advanced glycation end-product (AGE) appearing when arginine
      and lysine residues in proteins are cross-linked with carbonyl derivatives. This
      paper presents an improved method for the synthesis of pentosidine and reversed
      phase chromatography of this substance with fluorometric detection that enables
      sensitive (0.01 pmol/mg protein) and specific determination of pentosidine in
      plasma. Separation is done twice on the same C(18) Vydac 218TP54 column, first
      with trifluoroacetic acid and next with heptafluorobutyric acid as ion pair. The
      inter-day coefficient of variation is 6.4% at pentosidine concentration in plasma
      of 25 pmol/mg protein and 8% at 1.7 pmol/mg protein. Spectral properties of
      pentosidine exploited during identification of the substance with UV absorption
      and fluorescence detectors are described. Maximum of absorbance was observed at
      325 nm, maximum fluorescence at lambda(ex)/lambda(em)=330/373 nm. The method may
      prove useful for the study of processes associated with generation and
      accumulation of pentosidine in the body as a marker of AGE production in healthy
      subjects and patients with chronic renal failure.

PMID- 15571780
TI  - Construction and characterization of heterodimeric soluble quinoprotein glucose
      dehydrogenase.
AB  - In order to study in greater detail the subunit interaction of the homodimeric
      soluble quinoprotein glucose dehydrogenase (PQQGDH-B), we developed an effective
      method of creating heterodimeric PQQGDH-B. Two different homodimers are combined,
      one of which has a polyarginine tail (Arg-tail), and subjected to a protein
      dissociation/redimerization procedure. Separation of the mixture by cation
      exchange chromatography results in three peaks showing GDH activity, eluting at
      133, 231 and 273 mM NaCl concentration. These peaks were determined to correspond
      to the Arg-tailless homodimer, heterodimer, and Arg-tailed homodimer,
      respectively. To test this approach, we constructed and characterized
      heterodimeric PQQGDH-B composed of native (wild-type) and inactive mutant
      (His168Gln) subunits. The heterodimeric wild-type-His168Gln showed slightly
      decreased GDH activity and almost identical substrate specificity profile to the
      wild-type enzyme. Moreover, the Hill coefficient of the heterodimer was
      calculated as 1.13, indicating positive cooperativity.

PMID- 15571781
TI  - Staining of proteins on SDS polyacrylamide gels and on nitrocellulose membranes
      by Alta, a colour used as a cosmetic.
AB  - We describe here the use of Alta, a pre-existing scarlet-red stain of cosmetic
      use, for staining proteins on sodium dodecyl sulfate (SDS) polyacrylamide gels,
      as well as for a single step staining of gels and nitrocellulose membranes during
      Western blot analysis. This stain, which is composed of 0.8% Crocein scarlet
      (brilliant crocein) and 0.2% Rhodamine B, is inexpensive, easy to use and nearly
      as sensitive as Coomassie Brilliant Blue (CBB) R-250. The gels can be stained in
      10% Alta (2 h) and can be destained effectively only with 7% acetic acid as
      opposed to the conventional destainer (methanol/acetic acid/water) required for
      CBB-stained gels. In an alternative procedure, the proteins can be stained on the
      gel while electrophoresis by simply using 5% Alta in the top tank buffer and the
      stain can be viewed under UV-transilluminator. This procedure can also be used
      for Western blot analysis, as a single step procedure for staining of proteins on
      the gel as well as on the nitrocellulose membrane, as the stain is retained on
      the membrane after protein transfer. Thus, this staining procedure allows
      monitoring of proteins after each step in the Western blot, thereby eliminating
      the need to run separate gels for staining and Western blot analysis, and also
      the need for Ponceau Red S staining of the nitrocellulose membrane during Western
      blot analysis.

PMID- 15571782
TI  - In situ measurement of circular dichroism of DNA adsorbing onto a solid surface.
AB  - The adsorption process of DNA dissolved in aqueous solutions onto the surface of
      polyethyleneimine (PEI) has been examined by the observation of in situ circular
      dichroism (CD), including time-resolved measurements, to elucidate the
      conformation of DNA at the liquid/solid interface. The adsorption process can be
      characterized by two stages that are characterized in terms of CD. In the first
      stage, time (t)<700 s, a slight change in the time-resolved CD spectra of DNA is
      observed, whereas the value of the induced CD of the dye intercalated in DNA is
      constant. This result can be explained by the interaction between DNA and PEI
      during the adsorption at the liquid/solid interface. The weakness of the
      interaction is attributed to the geometrical restriction of this interface. In
      the second stage, t>700 s, where no further adsorption occurs, a change in the
      induced CD as well as in the CD of DNA is observed. This change in the induced CD
      can be interpreted as a significant conformational change of DNA for stabilizing
      the ion complex with PEI.

PMID- 15571783
TI  - Furthering the scientific foundation of pediatric bipolar disorder.

PMID- 15571784
TI  - Open-label prospective trial of risperidone in combination with lithium or
      divalproex sodium in pediatric mania.
AB  - OBJECTIVE: This prospective 6-month open trial examined the safety and efficacy
      of two combination therapies for manic or mixed episodes of pediatric bipolar
      disorder: (1) divalproex sodium plus risperidone (DVPX+Risp), or (2) lithium plus
      risperidone (Li+Risp). METHODS: Thirty-seven (37) subjects aged 5 and 18
      (age=12.1+/-3.5 years) with DSM IV current mixed or manic episode and Young Mania
      Rating Scale (YMRS) score >20 were sequentially assigned to either DVPX+Risp or
      Li+Risp in a 6-month, prospective open-label trial. Outcome measures included the
      YMRS, Clinical Global Impression Scale for Bipolar Disorder (CGI-BP), Child
      Depression Rating Scale-Revised (CDRS-R) as well as measures of safety and
      tolerability. RESULTS: Effect sizes (Cohen's d) based on change of YMRS scores
      from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp. Response rates
      (>or=50% change from baseline YMRS score at the end of study) were 80% for
      DVPX+Risp and 82.4% for Li+Risp. Both combination treatments were well tolerated.
      Significant improvements (p<0.001) from baseline were seen for mean scores on all
      efficacy measures, i.e., YMRS, CGI-BP, and CDRS-R. There were no significant
      group differences in safety or tolerability, and no serious adverse events during
      the 6-month trial. CONCLUSION: Both DVPX+Risp and Li+Risp show strong effects
      coupled with safety and tolerability in treating children and adolescents with
      manic or mixed episodes associated with type I bipolar disorder.

PMID- 15571785
TI  - Family-focused treatment for adolescents with bipolar disorder.
AB  - BACKGROUND: Research has begun to elucidate the optimal pharmacological
      treatments for pediatric-onset bipolar patients, but few studies have examined
      the role of psychosocial interventions as adjuncts to pharmacotherapy in
      maintenance treatment. This article describes an adjunctive family-focused
      psychoeducational treatment for bipolar adolescents (FFT-A). The adult version of
      FFT has been shown to be effective in forestalling relapses in two randomized
      clinical trials involving bipolar adults. METHODS: FFT-A is administered to
      adolescents who have had an exacerbation of manic, depressed, or mixed symptoms
      within the last 3 months. It is given in 21 outpatient sessions of
      psychoeducation, communication enhancement training, and problem solving skills
      training. We describe modifications to the adult FFT model to address the
      developmental issues and unique clinical presentations of pediatric-onset
      patients. RESULTS: An open treatment trial involving 20 bipolar adolescents (11
      boys, 9 girls; mean age 14.8+/-1.6) found that the combination of FFT-A and mood
      stabilizing medications was associated with improvements in depression symptoms,
      mania symptoms, and behavior problems over 1 year. LIMITATIONS: These early
      results are based on a small-scale open trial. CONCLUSIONS: Results from an
      ongoing randomized controlled trial will clarify whether combining FFT-A with
      pharmacotherapy improves the 2-year course of adolescent bipolar disorder. If the
      results are positive, then a structured manual-based psychosocial approach will
      be available for clinicians who treat adolescent bipolar patients in the
      community.

PMID- 15571786
TI  - A prospective follow-up study of pediatric bipolar disorder in boys with
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine patterns of persistence and remission in pediatric bipolar
      disorder attending to syndromatic, symptomatic, functional and affective
      definitions of remission of bipolar symptomatology in a longitudinal sample of
      ADHD children with comorbid bipolar disorder. METHODS: ADHD boys (128) were
      followed over 1- and 4-year follow-up assessments with structured diagnostic
      interviews to assess the persistence of psychiatric comorbidity. The course and
      duration of bipolar disorder was estimated by calculating the time from age at
      onset and the age at remission reported at either the 1- or 4-year follow-up
      assessments. RESULTS: Twenty-two (17%, Prevalent Cases) subjects met criteria for
      bipolar disorder at the baseline assessment. The average age of these subjects
      was 10.5+/-3.0 (range: 6 to 17 years) at baseline and 14.4+/-3.1 years of age at
      follow-up. The rate of remission was heavily dependent on the definition used.
      The rate of functional remission was the lowest and the rate of syndromatic
      remission was the highest. Regardless of the definition used, however, the
      disorder was chronic and lasted many years. LIMITATIONS: These data should be
      considered preliminary due to the sample size and the absence of mood symptom
      rating scales. CONCLUSIONS: That less than 20% of subjects attained functional
      remission or euthymia over the entire time period evaluated provides further
      evidence that pediatric bipolar disorder is a chronic mood disorder with a poor
      prognosis.

PMID- 15571787
TI  - The diagnosis of preschool bipolar disorder presenting with mania: open
      pharmacological treatment.
AB  - BACKGROUND: Diagnosis of bipolar disorder (BPD) in preschool children is
      controversial, although preliminary data suggest that children with BPD may
      present with classic manic symptoms in a more chronic, rapid cycling
      presentation. While children with BPD are extremely dysfunctional, presenting
      symptoms and symptom expression remains to be further defined. Clarification of
      the presentation of BPD in children could result in better treatment. METHODS:
      Thirty-one patients, ages 2-5 years, were identified by chart review of all
      children treated at our pediatric bipolar clinic. All available historical,
      symptom, and treatment information was collected and summarized. RESULTS:
      Patients were approximately 2:1 male: female, predominantly Caucasian, with an
      average age of symptom onset of 3 years. Most frequent presenting symptoms (100%)
      included irritability, increased energy, and aggression. Prominent symptoms
      (>80%) included euphoria, grandiosity, decreased need for sleep, pressured
      speech, and distractibility. Eighty percent of patients had concurrent Attention
      Deficit Hyperactivity Disorder (ADHD). Twenty-one of the 31 patients reported
      prior treatment attempts with either a stimulant or antidepressant without the
      protective benefit of a mood stabilizer, and of these, 13 (62%) reported a
      worsening of mood symptoms during that treatment period. Twenty-six of 31 were
      initially treated in our clinic openly with a mood stabilizer, primarily valproic
      acid, with a significant decrease in manic symptoms (p=0.03) following initial
      treatment. Long-term treatment demonstrated continued improvements from baseline
      (p=0.01). LIMITATIONS: The retrospective design of this study limits the
      conclusions that can be drawn. Due to the lack of a formal protocol, treatment
      was open and based on clinical judgment on an individual case basis. CONCLUSIONS:
      The symptom expression in these patients allowed for diagnosis according to DSM
      IV criteria. Treatment with mood stabilizers was clinically effective, with
      corresponding significant developmental benefits.

PMID- 15571788
TI  - Preschool-onset mania: incidence, phenomenology and family history.
AB  - OBJECTIVE: To ascertain the incidence of mania among preschool children
      presenting in a community mental health clinic over a 24-month period, to
      describe the signs and symptoms of the children meeting criteria for mania and
      present their family histories based on systematic diagnostic interview. METHODS:
      Forty children less than the age of 5 years presented between October 2001 and
      September 2003. Signs of mania were determined using a structured interview.
      Family history was determined via live, structured interview of parents. Those
      meeting the criteria for major depressive disorder (MDD) or bipolar disorder (BP)
      were classified as having mood disorder. RESULTS: Eleven of the 40 children
      (27.5%) met the criteria for mania, of which only 3 (27.3%) were mixed manic.
      Symptoms often included "classic" mania features (i.e. euphoric, elated mood),
      despite co-existing features of attention-deficit hyperactivity disorder (ADHD)-
      such as incessant, chaotic, even frenetic motor activation--in all of them. Seven
      of the 11 (63.6%) had at least one parent with BP and a total of 8 (72.7%) had a
      parental history of affective illness when parents with MDD were counted. One
      child without a first-degree relative with BP had a second degree relative with
      this illness. Thus, 8 of 11 (72.7%) had a relative with BP, and 9 (81.8%) a
      family history of mood disorder (counting both MDD and BP). LIMITATION: Open case
      series. CONCLUSION: There was a surprisingly high incidence of mania with
      classical features in this population. The family history data strongly support
      the view that these children have BP. Preschool mania appears to be strongly
      linked to the presence of familial affective illness. Admittedly, preschool mania
      is a controversial topic, and data from other centers is needed to further
      characterize its clinical and familial features.

PMID- 15571789
TI  - Further evidence of unique developmental phenotypic correlates of pediatric
      bipolar disorder: findings from a large sample of clinically referred
      preadolescent children assessed over the last 7 years.
AB  - BACKGROUND: A comparison of the prevalence, clinical correlates, and patterns of
      comorbidity among children with bipolar disorder (BPD) assessed in the early
      1990s (1st cohort) with those evaluated over the last 7 years (2nd cohort).
      METHOD: Subjects in both cohorts were children aged <or=12 years referred to a
      child psychiatry service and evaluated with identical assessment methods.
      Children with a DSM-III-R BPD diagnosis (1st cohort, n=43; 2nd cohort, n=129)
      were identified. For comparison purposes, we used attention-deficit/hyperactivity
      disorder (ADHD) children without BPD referred to the same clinic during the same
      time period (1st cohort, n=164; 2nd cohort, n=450). RESULTS: Analogous to 1st
      cohort findings, 2nd cohort results showed that (1) mania was identified in 17%
      of subjects; (2) the clinical picture was predominantly irritable and mixed, and
      the course was chronic; (3) BPD children frequently met criteria for major
      depression, ADHD, psychosis, and anxiety disorders; and (4) BPD children had high
      rates of psychiatric hospitalization and had evidence of severely impaired
      psychosocial functioning. CONCLUSION: These findings confirm that pediatric BPD
      is a severe clinical disorder afflicting a sizable number of referred
      preadolescent children. Its unique phenotypic features and patterns of
      comorbidity support the hypothesis that clinically referred pediatric bipolar
      disorder represents a very severe developmental subtype of bipolar disorder.

PMID- 15571790
TI  - Effects of adolescent manic symptoms on agreement between youth, parent, and
      teacher ratings of behavior problems.
AB  - BACKGROUND: Little is known about the extent to which manic symptoms might
      influence the self-report ratings of adolescents as compared to parent and
      teacher ratings, although there are clinical reasons to believe that mania would
      increase disagreement. METHODS: Parents and youths between the ages of 11 and 17
      years were evaluated with the Schedule for Affective Disorders and Schizophrenia
      for School-Age Children (KSADS), Young Mania Rating Scale, and Child Depression
      Rating Scale-Revised. Based on the KSADS results, subjects were assigned to
      either a bipolar spectrum group (e.g., meeting criteria for a diagnosis of
      bipolar I, II, cyclothymia, or NOS) or a "nonbipolar" group (including depressive
      disorders, disruptive behaviors disorders, and other axis I diagnoses). Parents
      and youths both completed the Achenbach rating scales and the General Behavior
      Inventory (GBI). Teachers also completed the Achenbach scales. RESULTS: Youth
      self-report of manic symptoms showed lower correlations with clinician ratings
      than did parent ratings. Youths with a bipolar diagnosis also show poorer
      agreement about their depressive symptoms. There was some evidence that bipolar
      youths underreported symptoms, even after controlling for parent history of mood
      disorder. The youth's own manic symptoms partially mediated the effect of a
      bipolar diagnosis on rater disagreement. LIMITATIONS: Diagnoses and mood ratings
      were based on both parent and youth interviews. CONCLUSIONS: Findings strongly
      suggest that cross-informant agreement can be substantially affected by the
      youth's own psychopathology. Youths with a bipolar diagnosis tend to underreport
      their manic symptoms compared to parental report. Results emphasize the
      importance of gathering collateral sources of information in evaluating juvenile
      mania, and also suggest that parent reported problems should not be discounted
      out of hand.

PMID- 15571791
TI  - The clinical characteristics of unipolar vs. bipolar major depression in ADHD
      youth.
AB  - OBJECTIVE: To investigate the characteristics of unipolar vs. bipolar depression
      in youth using a sample of children referred for a study on attention deficit
      hyperactivity disorder (ADHD). METHODS: We compared children with unipolar
      depression (N=109) to those with bipolar depression (N=43) using boys and girls
      (N=280) referred for a study on ADHD. Comparisons were made in characteristics of
      depression, comorbidity and family history. All diagnoses were made using the
      KSADS-E. RESULTS: In comparison to children with unipolar depression, children
      with bipolar depression were more likely to have met criteria for depression due
      to both "sad" and "mad" mood states as stated in the KSADS-E, have severe
      depression with suicidality, anhedonia and hopelessness. Children with bipolar
      depression were more likely to have comorbid conduct disorder, severe
      oppositional defiant disorder, agoraphobia, obsessive compulsive disorder and
      alcohol abuse, compared to children with unipolar depression. Bipolar depressed
      children had lower GAF scores and higher rates of hospitalization. Bipolar
      depression is associated with higher levels of psychiatric disorders in first
      degree relatives. CONCLUSIONS: In youth, bipolar depression is distinct from
      unipolar depression in quality and severity of symptoms, comorbidity and family
      history. This presentation can aid clinicians in identifying children and
      adolescents with bipolar disorder.

PMID- 15571792
TI  - A genome-wide scan of symptom dimensions in bipolar disorder pedigrees of adult
      probands.
AB  - Although twin and adoption show bipolar disorder (BP) has a strong genetic
      component, few chromosomal regions have been consistently implicated by molecular
      genetic studies. To address this issue, we sought to determine if quantitative
      dimensions of bipolar disorder symptoms would be useful for detecting genes that
      underlie the susceptibility to bipolar disorder. Subjects were 520 individuals
      diagnosed with bipolar I, bipolar II or schizoaffective disorder, bipolar type
      who had participated in the NIMH genetics initiative for bipolar disorder. We
      constructed symptom scores from 29 psychiatric symptoms recorded in the
      Diagnostic Interview for Genetic Studies (DIGS). Principal components factor
      analysis followed by a varimax rotation was used to extract symptom dimensions.
      Factor scores were calculated for all genotyped individuals in the sample,
      regardless of affection status. Heritable factors were used in a variance
      components linkage analysis, which utilized the exact likelihoods of allele
      sharing identical-by-descent for each pair of relatives within each pedigree. The
      principal components factor analysis resulted in five independent dimensions:
      depressed state, psychosis, sleep disturbances, psychomotor acceleration, and
      irritability. Two factors were significantly heritable: depression (h2=0.53,
      p<0.001) and irritable vs. euphoric mania (h2=0.35, p=0.03). These were
      subsequently used in a linkage analysis that resulted in LOD scores of <2.0,
      which are not statistically significant. The five constructs developed through
      factor analysis appear to be consistent with previous factor analyses. Notably,
      only the dimensions associated with the type of mood disturbance showed high
      heritability, which suggests that careful measurements of depression, euphoria
      and irritability may be particularly useful in clarifying the genetic etiology of
      bipolar disorder in future studies.

PMID- 15571793
TI  - Parametric neurocognitive task design: a pilot study of sustained attention in
      adolescents with bipolar disorder.
AB  - BACKGROUND: Disruption in attention is one of the core features of bipolar
      disorder (BP). Therefore, neurocognitive paradigms assessing brain function in
      response to tasks of increasing attentional difficulty may be useful to clarify
      the neurophysiology of bipolar disorder. The aim of this study was to obtain
      pilot performance data using a parametric task of sustained attention that might
      be useful as an experimental paradigm for future functional neuroimaging studies.
      We hypothesized that task performance would worsen as task difficulty increased
      in manic and euthymic bipolar and healthy subjects. Additionally, we hypothesized
      that the groups would exhibit a similar decline in task performance as level of
      task difficulty increased and that within each level of task difficulty there
      would be similar performance among groups. METHODS: A novel parametric Continuous
      Performance Task-Identical Pairs (CPT-IP) version was administered to manic
      (N=10) and euthymic (N=10) adolescents with bipolar disorder and healthy controls
      (N=10). RESULTS: There were no statistically significant group differences in
      task performance as measured by discriminability, percent correct, false positive
      hits, and reaction time. However, within each group, performance on all measures
      worsened with increased attentional difficulty (p<0.0001). There were no
      statistically significant task difficulty by group interactions. Furthermore,
      medication exposure and comorbid attention-deficit hyperactivity disorder were
      not associated with most measures of task performance. However, BP subjects who
      were treated with medications had slower task performance compared with BP
      subjects who were unmedicated. LIMITATIONS: Larger studies examining the effects
      of specific medication classes on task performance are necessary. CONCLUSIONS:
      The results of this pilot study suggest that manic and euthymic BP patients do
      not exhibit attentional dysfunction as compared to healthy adolescents using a
      novel parametric version of the CPT-IP. Furthermore, our parametric CPT-IP
      version may be useful as a novel parametric neurocognitive paradigm for future
      functional neuroimaging studies of bipolar adolescents.

PMID- 15571794
TI  - Reward-related processes in pediatric bipolar disorder: a pilot study.
AB  - BACKGROUND: Neuropsychological research on children with bipolar disorder (BPD)
      is scarce. Here, we examine reward-related behaviors in children with BPD using a
      Wheel of Fortune task in which subjects could win or lose money depending on
      their decisions. The intent of this work was to investigate performance
      differences between BPD and healthy children on a task that could be used in an
      fMRI environment to inform the neural substrates of reward processes in BPD. This
      study has no direct clinical implications. We hypothesized that relative to
      healthy children, children with BPD would select risky options more frequently,
      be less confident in a favorable outcome, and report stronger emotional responses
      to outcomes. METHODS: Forty-four children (22 BPD; 22 control) were compared on
      (i) decision-making with varying levels of risk, (ii) level of confidence in
      favorable outcomes, and (iii) responses to feedback. The task included a win-no
      win version and a lose-no lose version. RESULTS: Patterns of selection did not
      differ between groups. In the lose-no lose task, BPD patients were less confident
      than controls in favorable outcomes. BPD patients expressed greater
      dissatisfaction than controls at not winning in win-no win, and greater
      satisfaction than controls at not losing in lose-no lose. LIMITATIONS:
      Limitations of this study included that the children with BPD were mostly in a
      depressed state, were medicated, and had co-morbid disorders. CONCLUSIONS: This
      is the first experimental study to examine associations between pediatric BPD and
      reward-related behaviors. Although we failed to detect abnormalities in risky
      decision-making in children with BPD, we found significant differences between
      groups in both confidence ratings and response to feedback, consistent with our
      predictions. Our ultimate goal is to use this task in the fMRI environment to
      gain a better understanding of the neural correlates of reward-related processes
      in pediatric BPD.

PMID- 15571795
TI  - Identification of DNA copy number changes in microdissected serous ovarian cancer
      tissue using a cDNA microarray platform.
AB  - We have established a method for using a cDNA array platform in combination with
      degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and
      taramide signal amplification (TSA) to identify DNA copy number abnormalities
      (CNA) in cancer cell lines and cancer cells procured with laser-based
      microdissection. To determine the sensitivity and specificity for detecting
      single-copy gain and loss, receiver-operator curve analysis was performed on
      hybridization signal ratios generated from non-DOP and DOP amplified female and
      male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.12 and 1.07
      average signal ratio for X-chromosomal genes versus autosomal genes provided a
      sensitivity and specificity of 50 and 79%, respectively, for non-DOP amplified
      DNA and a sensitivity and specificity of 50 and 72%, respectively, for DOP
      amplified DNA. We used this approach to identify DNA copy number abnormalities in
      the ovarian cancer cell line OVCA633, which has previously been shown to have 12p
      amplification. Transcription profiling of OVCA633 was also performed. Two
      amplified and overexpressed genes located on 12p11, KRAS2 and LRMP, were
      identified; these were validated with quantitative real-time PCR. Subsequently,
      the same approach was used to identify CNAs and gene expression alterations in 11
      microdissected serous ovarian adenocarcinoma cases. Validated data revealed
      amplification and overexpression of ERBB3 and FOS and deletion and
      underexpression of KRT6 and APXL in more than 50% of the tissue samples. These
      results show the feasibility of using the cDNA array platform to identify changes
      in DNA and mRNA copy number simultaneously in microdissected tumor tissues.

PMID- 15571796
TI  - Global search for chromosomal abnormalities in infiltrating ductal carcinoma of
      the breast using array-comparative genomic hybridization.
AB  - Array-comparative genomic hybridization (a-CGH) is a molecular cytogenetic
      technique for detection of multiple chromosomal abnormalities in genomic DNA
      samples. Using an a-CGH with 287 probes, we examined 14 cases of breast
      infiltrating ductal carcinoma (IDCA) that had previously been classified by
      fluorescent in situ hybridization (FISH) as either human epidermal growth factor
      receptor-2 positive (HER2+) or HER2- and analyzed the data by hierarchical, K
      means, and principal component analyses. The aim of the study was to identify the
      genetic abnormalities that are present in breast IDCAs and determine if the
      global status of 287 cytogenetic locations could be used as a more objective
      method for breast IDCA classification. Concordance between FISH and a-CGH at the
      HER2 locus was 78.6% (11/14). In general, a-CGH detected more abnormalities in
      HER2+ cases. In HER 2+ cases, chromosomes 1, 2, 3, 7, 9, 17, and 20 had more
      regions that showed statistically significant (P < or = 0.01) changes in DNA copy
      number. Among all the aberrant cytogenetic locations detected, 20q13, 7p12.3
      approximately p12.1, and 17q23.2 approximately q25.3, which contain among others,
      genes for TNFRSF6B, EGFR, and TK1 showed statistically significant gains (P < or
      = 0.01) in 83, 66.7, and 50% of the HER2+ IDCA cases, respectively. Chromosome
      location 8q24.12 approximately q24.13 was the only region that showed consistent
      amplification in approximately 50% of the HER2- cases. Unsupervised hierarchical
      and K-means cluster analyses and principal component analysis using the DNA copy
      number status of 287 cytogenetic locations or the 177 cytogenetic locations that
      showed statistically significant differences revealed a cluster consisting of
      mainly HER2- IDCA cases. Even though this study demonstrates the usefulness of a
      CGH in the rapid identification of aberrant DNA regions in tumor samples, we
      conclude that an array-CGH with more than 287 probes will be needed for a more
      precise mapping of DNA aberrations at the global level.

PMID- 15571797
TI  - Genome signatures of colon carcinoma cell lines.
AB  - In cancer biology, cell lines are often used instead of primary tumors because of
      their widespread availability and close reflection of the in vivo state. Cancer
      is a genetic disease, commonly caused by small- and large-scale DNA
      rearrangements. Therefore, it is essential to know the genomic profiles of tumor
      cell lines to enable their correct and efficient use as experimental tools. Here,
      we present a comprehensive study of the genomic profiles of 20 colon cancer cell
      lines combining conventional karyotyping (G-banding), comparative genomic
      hybridization (CGH), and multicolor fluorescence in situ hybridization (M-FISH).
      Major differences between the microsatellite instability (MSI) and chromosome
      instability (CIN) cell lines are shown; the CIN cell lines exhibited complex
      karyotypes involving many chromosomes (mean: 8.5 copy number changes), whereas
      the MSI cell lines showed considerably fewer aberrations (mean: 2.6). The 3
      techniques complement each other to provide a detailed picture of the numerical
      and structural chromosomal changes that characterize cancer cells. Therefore, 7
      of the cell lines (Colo320, EB, Fri, IS2, IS3, SW480, and V9P) are here
      completely karyotyped for the first time and, among these, 5 have not previously
      been cytogenetically described. By hierarchical cluster analysis, we show that
      the cell lines are representative models for primary carcinomas at the genome
      level. We also present the genomic profiles of an experimental model for tumor
      progression, including 3 cell lines (IS1, IS2, and IS3) established from a
      primary carcinoma, its corresponding liver- and peritoneal metastasis from the
      same patient. To address the question of clonality, we compared the genome of 3
      common cell lines grown in 2 laboratories. Finally, we compared all our results
      with previously published CGH data and karyotypes of colorectal cell lines. In
      conclusion, the large variation in genetic complexity of the cell lines
      highlights the importance of a comprehensive reference of genomic profiles for
      investigators engaged in functional studies using these research tools.

PMID- 15571798
TI  - Fluorescence in situ hybridization characterization of different cryptic BCR-ABL
      rearrangements in chronic myeloid leukemia.
AB  - Using fluorescence in situ hybridization probes, obtained from bacterial
      artificial chromosome (BAC) libraries that relate to sequences either side of the
      BCR and ABL genes, this study characterized four chronic myeloid leukemia cases
      with cryptic BCR-ABL rearrangements. Each case showed evidence of a different
      underlying mechanism: one case showed a microinsertion of BCR into ABL, another a
      microinsertion of ABL into BCR, and the third showed a complex rearrangement
      including deletion of adjacent flanking sequences, consistent with the reverse
      translocation model of cryptic rearrangement. The fourth case also showed
      evidence of a more complex rearrangement involving chromosome 1.

PMID- 15571799
TI  - Complex translocation (8;12;21): a new variant of t(8;21) in acute myeloid
      leukemia.
AB  - Variants of the t(8;21)(q22;q22) involving chromosomes 8, 21, and other
      chromosomes account for approximately 3% of all t(8;21)(q22;q22) in acute myeloid
      leukemia (AML) patients. In this paper, we report a case of AML-M2 with a
      t(8;12;21)(q22;p12 approximately p13;q22) associated with chromosomal
      abnormalities, including loss of the Y chromosome and trisomy 8q22 approximately
      qter. Using a dual-color fluorescence in situ hybridization (FISH) analysis with
      ETO and AML1 probes, we demonstrated an ETO/AML1 fusion signal on the derivative
      chromosome 8. Using whole painting probes for chromosomes 8 and 12, we
      demonstrated a three-way translocation, t(8;12;21)(q22;p12 approximately
      p13;q22). Reverse transcription polymerase chain reaction (RT-PCR) analysis
      showed the presence of AML1/ETO fusion transcript. The present case highlights
      the importance of the combination of approaches, i.e., standard karyotyping,
      FISH, and RT-PCR, for the detection of variants of t(8;21)(q22;q22), shedding
      light on region 8q22 approximately qter which could harbor potential genes
      responsible for leukemogenesis.

PMID- 15571800
TI  - Specificity of interphase fluorescence in situ hybridization for detection of
      chromosome aberrations in tumor pathology.
AB  - Interphase fluorescence in situ hybridization (IFISH) is an interesting and
      intriguing cytogenetic approach in the study of tumor chromosomal abnormalities
      when metaphases are not available. This technique can be applied to different
      types of tumor nuclei, including imprinted nuclei (IM), nuclei obtained from
      conventional cytogenetic procedures (PB), frozen nuclei, paraffin-embedded nuclei
      (PE), and nuclei extracted from paraffin-embedded sections (EX). IFISH is a high
      sensitivity approach in tumor studies that can give evidence of genetic
      aberrations present in a small percentage of cells that are likely to escape
      detection if only molecular techniques are applied. Despite its high sensitivity
      and versatility, IFISH is an indirect cytogenetic method and needs controls to
      have adequate specificity. This study includes present data obtained in IFISH
      experiments using different types of probes (alpha-satellite and YAC clones)
      hybridized on different types of normal control nuclei, such as PB, IM, EX, and
      PE nuclei, to define the threshold level for monosomy and trisomy of different
      chromosomal regions. My findings demonstrate that the cut-off values depend both
      on the types of probes and on the types of target nuclei. Therefore, even if
      IFISH is a versatile, high-sensitivity technique for detecting chromosomal
      abnormalities, the lack of accurate controls may result in the misdiagnosis of
      some abnormalities.

PMID- 15571801
TI  - Six novel heterozygous MLH1, MSH2, and MSH6 and one homozygous MLH1 germline
      mutations in hereditary nonpolyposis colorectal cancer.
AB  - Most hereditary nonpolyposis colorectal cancer (HNPCC) cases are caused by
      germline mutations of mismatch repair (MMR) genes (i.e., MLH1, MSH2, or MSH6).
      Here we describe six novel mutations in patients referred for genetic assessment.
      All of these mutations lead to premature translation termination. Five single
      base pair deletions lead to frameshift (MLH1: g.38-39insCCCA, g.1971del.T; MSH2:
      g.163del.C, g.746del.A; MSH6: g.3320del.A) and one nonsense mutation in MSH2
      g.1030C>T leads to a stop codon: p.Q344X. In one patient, the previously
      described MLH1 nonsense mutation g.806C>G was found in a homozygous state. In
      this patient, the familial histories of both the mother and father suggested
      HNPCC syndrome. This patient developed colon cancer at 22 years of age,
      suggesting a more aggressive phenotype. The results of our study provide further
      insight into the mutational spectrum of MMR genes in HNPCC families.

PMID- 15571802
TI  - Complex t(8;14;21)(q22;q13;q22), a variant of t(8;21), with t(15;21)(q15;p11) in
      a patient with acute myelogenous leukemia (M1).

PMID- 15571803
TI  - An extra X chromosome as a sole abnormality in relapse of an adult acute
      lymphoblastic leukemia.

PMID- 15571804
TI  - Death gives birth to life: the essential role of the ubiquitin-proteasome system
      in biology.

PMID- 15571805
TI  - The ubiquitin system: pathogenesis of human diseases and drug targeting.
AB  - With the many processes and substrates targeted by the ubiquitin pathway, it is
      not surprising to find that aberrations in the system underlie, directly or
      indirectly, the pathogenesis of many diseases. While inactivation of a major
      enzyme such as E1 is obviously lethal, mutations in enzymes or in recognition
      motifs in substrates that do not affect vital pathways or that affect the
      involved process only partially may result in a broad array of phenotypes.
      Likewise, acquired changes in the activity of the system can also evolve into
      certain pathologies. The pathological states associated with the ubiquitin system
      can be classified into two groups: (a) those that result from loss of function
      mutation in a ubiquitin system enzyme or in the recognition motif in the target
      substrate that lead to stabilization of certain proteins, and (b) those that
      result from gain of function-abnormal or accelerated degradation of the protein
      target. Studies that employ targeted inactivation of genes coding for specific
      ubiquitin system enzymes and substrates in animals can provide a more systematic
      view into the broad spectrum of pathologies that may result from aberrations in
      ubiquitin-mediated proteolysis. Better understanding of the processes and
      identification of the components involved in the degradation of key regulatory
      proteins will lead to the development of mechanism-based drugs that will target
      specifically only the involved proteins.

PMID- 15571806
TI  - The proteasome: a proteolytic nanomachine of cell regulation and waste disposal.
AB  - The final destination of the majority of proteins that have to be selectively
      degraded in eukaryotic cells is the proteasome, a highly sophisticated
      nanomachine essential for life. 26S proteasomes select target proteins via their
      modification with polyubiquitin chains or, in rare cases, by the recognition of
      specific motifs. They are made up of different subcomplexes, a 20S core
      proteasome harboring the proteolytic active sites hidden within its barrel-like
      structure and two 19S caps that execute regulatory functions. Similar complexes
      equipped with PA28 regulators instead of 19S caps are a variation of this theme
      specialized for the production of antigenic peptides required in immune response.
      Structure analysis as well as extensive biochemical and genetic studies of the
      26S proteasome and the ubiquitin system led to a basic model of substrate
      recognition and degradation. Recent work raised new concepts. Additional factors
      involved in substrate acquisition and delivery to the proteasome have been
      discovered. Moreover, first insights in the tasks of individual subunits or
      subcomplexes of the 19S caps in substrate recognition and binding as well as
      release and recycling of polyubiquitin tags have been obtained.

PMID- 15571807
TI  - Inhibitors of the eukaryotic 20S proteasome core particle: a structural approach.
AB  - The ubiquitin-proteasome pathway is particularly important for the regulated
      degradation of various proteins which control a vast array of biological
      processes. Therefore, proteasome inhibitors are promising candidates for anti
      tumoral or anti-inflammatory drugs. N-Acetyl-Leu-Leu-Norleucinal (Ac-LLN-al, also
      termed calpain inhibitor I) was one of the first proteasome inhibitors discovered
      and has been widely used to study the 20S proteasome core particle (CP) function
      in vivo, despite its lack of specificity. Vinyl sulfones, like Ac-PRLN-vs, show
      covalent binding of the beta-carbon atom of the vinyl sulfone group to the
      Thr1Ogamma only of subunit beta2. However, vinyl sulfones have similar
      limitations as peptide aldehydes as they have been reported also to bind and
      block intracellular cysteine proteases. A more specific proteasome inhibitor is
      the natural product lactacystin, which can be isolated from Streptomyces. It was
      found that this compound forms an ester bond only to the Thr1Ogamma of the
      chymotrypsin-like active subunit beta5 due to specific P1 interactions. In
      contrast to most other proteasome inhibitors, the natural alpha',beta'
      epoxyketone peptide epoxomicin binds specifically to the small class of N
      terminal nucleophilic (Ntn) hydrolases (CPs belong to this protease family) with
      the formation of a morpholino adduct. All previously described proteasome
      inhibitors bind covalently to the proteolytic active sites. However, as the
      proteasome is involved in a variety of biological important functions, it is of
      particular interest to block the CP only for limited time in order to reduce
      cytotoxic effects. Recently, the binding mode of the natural specific proteasome
      inhibitor TMC-95 obtained from Apiospora montagnei was investigated. The crystal
      structure revealed that the TMC-95 blocks the active sites of the CP
      noncovalently in the low nanomolar range. This review summarizes the current
      structural knowledge of inhibitory compounds bound to the CP, showing the
      proteasome as a potential target for drug development in medical research.

PMID- 15571808
TI  - The COP9 signalosome (CSN): an evolutionary conserved proteolysis regulator in
      eukaryotic development.
AB  - The COP9 signalosome (CSN) is a multiprotein complex of the ubiquitin-proteasome
      pathway. CSN is typically composed of eight subunits, each of which is related to
      one of the eight subunits that form the lid of the 26S proteasome regulatory
      particle. CSN was first identified in Arabidopsis where it is required for the
      repression of photomorphogenic seedling development in the dark. CSN or CSN
      related complexes have by now been reported from most eukaryotic model organisms
      and CSN has been implicated in a vast array of biological processes. It is widely
      accepted that CSN directly interacts with cullin-containing E3 ubiquitin ligases,
      and that CSN is required for their proper function. The requirement of CSN for
      proper E3 function may at least in part be explained by the observation that CSN
      subunit 5 (CSN5) is the isopeptidase that deconjugates the essential ubiquitin
      like Nedd8 modification from the E3 cullin subunit. In addition to its
      interaction with E3s, CSN may also regulate proteolysis by its association with
      protein kinases and deubiquitylating enzymes. This review provides a summary of
      the role of CSN in regulating protein degradation and in eukaryotic development.

PMID- 15571809
TI  - Ubiquitin: structures, functions, mechanisms.
AB  - Ubiquitin is the founding member of a family of structurally conserved proteins
      that regulate a host of processes in eukaryotic cells. Ubiquitin and its
      relatives carry out their functions through covalent attachment to other cellular
      proteins, thereby changing the stability, localization, or activity of the target
      protein. This article reviews the basic biochemistry of these protein conjugation
      reactions, focusing on ubiquitin itself and emphasizing recent insights into
      mechanism and specificity.

PMID- 15571810
TI  - Ubiquitin family proteins and their relationship to the proteasome: a structural
      perspective.
AB  - Many biological processes rely on targeted protein degradation, the dysregulation
      of which contributes to the pathogenesis of various diseases. Ubiquitin plays a
      well-established role in this process, in which the covalent attachment of
      polyubiquitin chains to protein substrates culminates in their degradation via
      the proteasome. The three-dimensional structural topology of ubiquitin is highly
      conserved as a domain found in a variety of proteins of diverse biological
      function. Some of these so-called "ubiquitin family proteins" have recently been
      shown to bind components of the 26S proteasome via their ubiquitin-like domains,
      thus implicating proteasome activity in pathways other than protein degradation.
      In this chapter, we provide a structural perspective of how the ubiquitin family
      of proteins interacts with the proteasome.

PMID- 15571811
TI  - Ubiquitin and endocytic internalization in yeast and animal cells.
AB  - Endocytosis is involved in a wide variety of cellular processes, and the
      internalization step of endocytosis has been extensively studied in both lower
      and higher eukaryotic cells. Studies in mammalian cells have described several
      endocytic pathways, with the main emphasis on clathrin-dependent endocytosis.
      Genetic studies in yeast have underlined the critical role of actin and actin
      binding proteins, lipid modification, and the ubiquitin conjugation system. The
      combined results of studies of endocytosis in higher and lower eukaryotic cells
      reveal an interesting interplay in the two systems, including a crucial role for
      ubiquitin-associated events. The ubiquitylation of yeast cell-surface proteins
      clearly acts as a signal triggering their internalization. Mammalian cells
      display variations on the common theme of ubiquitin-linked endocytosis, according
      to the cell-surface protein considered. Many plasma membrane channels,
      transporters and receptors undergo cell-surface ubiquitylation, required for the
      internalization or later endocytic steps of some cell-surface proteins, whereas
      for others, internalization involves interaction with the ubiquitin conjugation
      system or with ancillary proteins, which are themselves ubiquitylated. Epsins and
      Eps15 (or Eps15 homologs), are commonly involved in the process of endocytosis in
      all eukaryotes, their critical role in this process stemming from their capacity
      to bind ubiquitin, and to undergo ubiquitylation.

PMID- 15571812
TI  - SUMO protein modification.
AB  - SUMO (small ubiquitin-related modifier) family proteins are not only structurally
      but also mechanistically related to ubiquitin in that they are
      posttranslationally attached to other proteins. As ubiquitin, SUMO is covalently
      linked to its substrates via amide (isopeptide) bonds formed between its C
      terminal glycine residue and the epsilon-amino group of internal lysine residues.
      The enzymes involved in the reversible conjugation of SUMO are similar to those
      mediating the ubiquitin conjugation. Since its discovery in 1996, SUMO has
      received a high degree of attention because of its intriguing and essential
      functions, and because its substrates include a variety of biomedically important
      proteins such as tumor suppressor p53, c-jun, PML and huntingtin. SUMO
      modification appears to play important roles in diverse processes such as
      chromosome segregation and cell division, DNA replication and repair, nuclear
      protein import, protein targeting to and formation of certain subnuclear
      structures, and the regulation of a variety of processes including the
      inflammatory response in mammals and the regulation of flowering time in plants.

PMID- 15571813
TI  - A hitchhiker's guide to the cullin ubiquitin ligases: SCF and its kin.
AB  - The SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase family was discovered through
      genetic requirements for cell cycle progression in budding yeast. In these
      multisubunit enzymes, an invariant core complex, composed of the Skp1 linker
      protein, the Cdc53/Cul1 scaffold protein and the Rbx1/Roc1/Hrt1 RING domain
      protein, engages one of a suite of substrate adaptors called F-box proteins that
      in turn recruit substrates for ubiquitination by an associated E2 enzyme. The
      cullin-RING domain-adaptor architecture has diversified through evolution, such
      that in total many hundreds of distinct SCF and SCF-like complexes enable
      degradation of myriad substrates. Substrate recognition by adaptors often depends
      on posttranslational modification of the substrate, which thus places substrate
      stability under dynamic regulation by intracellular signaling events. SCF
      complexes control cell proliferation through degradation of critical regulators
      such as cyclins, CDK inhibitors and transcription factors. A plethora of other
      processes in development and disease are controlled by other SCF-like complexes,
      including those based on Cul2-SOCS-box adaptor protein and Cul3-BTB domain
      adaptor protein combinations. Recent structural insights into SCF-like complexes
      have begun to illuminate aspects of substrate recognition and catalytic reaction
      mechanisms.

PMID- 15571814
TI  - Cooperation of molecular chaperones with the ubiquitin/proteasome system.
AB  - Molecular chaperones and energy-dependent proteases have long been viewed as
      opposing forces that control protein biogenesis. Molecular chaperones are
      specialized in protein folding, whereas energy-dependent proteases such as the
      proteasome mediate efficient protein degradation. Recent data, however, suggest
      that molecular chaperones directly cooperate with the ubiquitin/proteasome system
      during protein quality control in eukaryotic cells. Modulating the intracellular
      balance of protein folding and protein degradation may open new strategies for
      the treatment of human diseases that involve chaperone pathways such as cancer
      and diverse amyloid diseases.

PMID- 15571815
TI  - Mechanism and function of deubiquitinating enzymes.
AB  - Attachment of ubiquitin to proteins is a crucial step in many cellular regulatory
      mechanisms and contributes to numerous biological processes, including embryonic
      development, the cell cycle, growth control, and prevention of neurodegeneration.
      In these diverse regulatory settings, the most widespread mechanism of ubiquitin
      action is probably in the context of protein degradation. Polyubiquitin
      attachment targets many intracellular proteins for degradation by the proteasome,
      and (mono)ubiquitination is often required for down-regulating plasma membrane
      proteins by targeting them to the vacuole (lysosome). Ubiquitin-protein
      conjugates are highly dynamic structures. While an array of enzymes directs the
      conjugation of ubiquitin to substrates, there are also dozens of deubiquitinating
      enzymes (DUBs) that can reverse the process. Several lines of evidence indicate
      that DUBs are important regulators of the ubiquitin system. These enzymes are
      responsible for processing inactive ubiquitin precursors, proofreading ubiquitin
      protein conjugates, removing ubiquitin from cellular adducts, and keeping the 26S
      proteasome free of inhibitory ubiquitin chains. The present review focuses on
      recent discoveries that have led to a better understanding the mechanisms and
      physiological roles of this diverse and still poorly understood group of enzymes.
      We also discuss briefly some of the proteases that act on ubiquitin-like protein
      (UBL) conjugates and compare them to DUBs.

PMID- 15571816
TI  - Productive RUPture: activation of transcription factors by proteasomal
      processing.
AB  - Proteasomes usually degrade proteins completely into small peptides. In a few
      cases, however, proteasomal degradation rather results in protein processing,
      thereby yielding proteins of different biological activity. This process, termed
      "regulated ubiquitin/proteasome-dependent processing" or RUP, is essential for
      the function of certain transcription factors and crucial for their regulation.
      Examples are proteins of the mammalian NF-kappaB family and the yeast proteins
      SPT23 and MGA2. In this review, we summarize the available data and suggest a
      mechanistic model for proteasomal processing.

PMID- 15571817
TI  - Endoplasmic reticulum-associated protein degradation--one model fits all?
AB  - The endoplasmic reticulum (ER) is the eukaryotic organelle where most secretory
      proteins are folded for subsequent delivery to their site of action. Proper
      folding of newly synthesized proteins is monitored by a stringent ER quality
      control system. This system recognizes misfolded or unassembled proteins and
      prevents them from reaching their final destination. Instead, they are extracted
      from the ER, polyubiquitinated and degraded by the cytosolic proteasome. With the
      identification of novel components and substrates, a more and more complex
      picture of this process emerges in which distinct pathways target different sets
      of substrates for destruction.

PMID- 15571818
TI  - The proteasome and MHC class I antigen processing.
AB  - By generating peptides from intracellular antigens, which are then presented to T
      cells, the ubiquitin/26S proteasome system plays a central role in the cellular
      immune response. Under the control of interferon-gamma the proteolytic properties
      of the proteasome are adapted to the requirements of the immune system.
      Interferon-gamma induces the formation of immunoproteasomes and the synthesis of
      the proteasome activator PA28. Both alter the proteolytic properties of the
      proteasome complex and enhance proteasomal function in antigen presentation.
      Thus, a combination of several of regulatory events tunes the proteasome system
      for maximal efficiency in the generation of MHC class I antigens.

PMID- 15571819
TI  - Ubiquitin, proteasome and parkin.
AB  - The ubiquitin-proteasome system (UPS) is important for intracellular proteolysis,
      and is responsible for a diverse array of biologically important cellular
      processes, such as cell-cycle progression, signaling cascades and developmental
      programs. This system is also involved in the protein quality control, which
      maintains the health of the cell. Thus, the UPS provides a clue for understanding
      of the molecular mechanisms underlying various neurodegenerative diseases. In the
      last decade, we witnessed a tremendous progress in uncovering the mechanisms of
      Parkinson's disease (PD). Of the several genes that can cause familial PD,
      parkin, the causative gene of autosomal recessive juvenile parkinsonism (ARJP),
      is of a special interest because it encodes an ubiquitin-protein ligase, which
      covalently attaches ubiquitin to target proteins, designating them for
      destruction by the proteasome. This review summarizes recent studies on the UPS
      pathway with a special reference to parkin, focusing on how parkin is linked to
      the pathogenesis of ARJP.

PMID- 15571820
TI  - Should mitral valve area assessment in patients with mitral stenosis be based on
      anatomical or on functional evaluation? A plea for 3D echocardiography as the new
      clinical standard.

PMID- 15571821
TI  - Alcohol intake and markers of inflammation.

PMID- 15571822
TI  - Coronary artery bypass grafting on the beating heart: surgical revascularization
      for the next decade?
AB  - This review considers whether coronary artery bypass grafting (CABG) performed on
      the beating heart (off-pump or OPCAB) will supersede conventional CABG utilizing
      cardiopulmonary bypass (CPB) and cardioplegic arrest as the accepted gold
      standard. Randomized controlled trials, case-matched reports and observational
      studies have demonstrated lower morbidity in off-pump compared to conventional on
      pump CABG with equivalent mid-term outcome at a significantly lower cost.
      Patients referred for surgical revascularization are increasingly elderly with
      more co-morbid medical conditions and elimination of CPB-related morbidity in
      these groups is associated with the most pronounced improvements in outcome, at
      least in observational studies. Long-term outcome, and in particular, long-term
      graft patency following OPCAB has not yet been reported. A barrier to the more
      widespread acceptance of OPCAB is the poor provision for training in off-pump
      techniques although structured cardiothoracic training that includes OPCAB
      surgery has been shown to be both possible and safe for patients. The evidence
      available to date therefore strongly supports the assertion that OPCAB may become
      the new gold standard in surgical revascularization. Whether it will ultimately
      replace conventional CABG, however, is dependent on the results of long-term
      patency studies and the wider development of adequate training programmes.

PMID- 15571823
TI  - Non-invasive assessment of mitral valve area during percutaneous balloon mitral
      valvuloplasty: role of real-time 3D echocardiography.
AB  - BACKGROUND: In the last decade, multiple studies depicted discrepancies between
      mitral valvular orifice area (MVA) measurements obtained with the pressure half
      time (PHT) method and invasive methods during the immediate post-percutaneous
      mitral valvuloplasty (PMV) period. Our aim was to assess the accuracy of Real
      Time 3D echo (RT3D) to measure the MVA in the immediate post-PMV period. The
      invasively determined MVA was used as the gold standard. METHODS AND RESULTS: We
      studied 29 patients with rheumatic mitral stenosis from two centres (27 women;
      mean age 48.2+/-11.3 years), all of which had underwent PMV. MVA was calculated
      before and after PMV using the PHT method, 2D echo planimetry, RT3D echo
      planimetry and invasive determination (Gorlin's method). The RT3D MVA assessment
      showed a better agreement with the invasively derived MVA before and in the
      immediate post-PMV period (Bland-Altman analysis: Average difference between both
      methods and limits of agreement: 0.01 (-0.31 to 0.33) cm(2) and -0.12 (-0.71 to
      0.47) cm(2)) before and immediately after the PMV, respectively. CONCLUSIONS:
      RT3D is a feasible and accurate technique for measuring MVA in patients with
      RMVS. It has the best agreement with the invasively determined MVA, particularly
      in the immediate post-PMV period.

PMID- 15571824
TI  - Overall alcohol intake, beer, wine, and systemic markers of inflammation in
      western Europe: results from three MONICA samples (Augsburg, Glasgow, Lille).
AB  - AIM: Anti-inflammatory effects of moderate alcohol consumption have been proposed
      to explain why moderate alcohol intake lowers coronary heart disease risk. We
      investigated the relationship between overall alcohol, beer or wine consumption
      and markers of systemic inflammation in three different geographical areas in
      Europe. METHODS AND RESULTS: Cross-sectional samples, each representative of the
      general population from Germany, Scotland, and France (MONICA Augsburg 1994/95,
      2275 men and 2186 women, 25-74 years; Glasgow MONICA 1994/95, 561/616, 25-74
      years, and MONICA Lille 1994/95, 581/574, 35-64 years) were studied. Alcohol
      intake was assessed by standardized interview. Adjusted means of C-reactive
      protein (CRP), fibrinogen, white blood cell (WBC) count, plasma viscosity (PV),
      and albumin were calculated among categories of alcohol intake, and separately
      for beer or wine consumption, by multiple linear regression. Self-reported
      moderate daily alcohol intake up to 40 g was associated with lower concentrations
      of CRP, fibrinogen, PV and WBC count, compared to non-drinking and heavy
      drinking, even after adjustment for various potential confounders. CONCLUSIONS:
      Moderate consumption of either wine or beer is associated with lower levels of
      systemic inflammatory markers in three different European areas, suggesting that
      ethanol itself might be largely responsible for the potential anti-inflammatory
      effects of these beverages.

PMID- 15571825
TI  - Short-term benefit of smoking cessation in patients with coronary heart disease:
      estimates based on self-reported smoking data and serum cotinine measurements.
AB  - AIMS: To assess the short-term impact of smoking and smoking cessation measured
      by self-report and by serum cotinine on the risk of secondary cardiovascular
      disease events (CVD events). METHODS AND RESULTS: Cohort study among participants
      of an in-patient 3-week rehabilitation programme following an acute coronary
      syndrome or coronary artery revascularization. Smoking status at baseline was
      assessed by self-report (beginning of the rehabilitation programme, rehab) and
      serum cotinine (end of rehab). Active follow-up was conducted one year later.
      Subsequent CVD events were observed in 139 of the 967 patients. Both self
      reported smoking status (odds ratio (OR) compared to continued smokers: recent
      quitters 0.96, former smokers 0.83, never smokers 0.54, p for trend 0.04) and
      serum cotinine (OR 0.59 (95% confidence interval (CI) 0.36-0.97) for cotinine
      negative compared to cotinine-positive subjects) were associated with the
      occurrence of a secondary CVD event. After reclassification of all cotinine
      positive subjects to continued smokers and cotinine-negative self-reported
      smokers to recent quitters, this association became even stronger. The OR now
      reached 0.71 (95% CI interval 0.38-1.33) for recent quitters, 0.64 (0.36-1.11)
      for former smokers and 0.44 (0.24-0.81) for never smokers (p-value for
      trend=0.009). CONCLUSION: The benefits of non-smoking and smoking cessation in
      cardiac patients are beyond controversy and might even be larger than suggested
      by previous studies which exclusively relied on self-reported smoking status.

PMID- 15571826
TI  - The apolipoprotein E polymorphism is associated with circulating C-reactive
      protein (the Ludwigshafen risk and cardiovascular health study).
AB  - BACKGROUND: Statins and cholesterol absorption inhibitors lower the concentration
      of C-reactive protein (CRP). The genetic polymorphism of apolipoprotein (apo) E
      is a strong endogenous determinant of sterol homeostasis. We therefore examined
      the relationship of CRP to the apoE polymorphism. METHODS AND RESULTS: We studied
      739 and 570 subjects with or without stable angiographic coronary artery disease
      (CAD), respectively. In carriers of apoE2, apoB was lower (P<0.001) than in
      apoE3/3 homozygotes; in individuals with apoE3/4 and apoE4/4, it was higher
      (P<0.001). Both in the presence and absence of CAD, CRP was higher in carriers of
      apoE2 (P=0.002) and apoE3/3 homozygotes (P=0.032) than in individuals with
      apoE3/4 or apoE4/4. Fibrinogen and white cell count were not related to the apoE
      genotype. CRP was associated with CAD. Compared to the lowest tertile, crude odds
      ratios were 1.87 (95% confidence interval (CI), 1.43-2.45, P<0.001) and 2.24 (95%
      CI, 1.71-2.94, P<0.001) in the second and third tertile. In carriers of apoE2,
      the use of tertiles defined in controls with apoE2 only diminished the odds
      ratios for CAD. In apoE3/4 heterozygotes or apoE4/4 homozygotes, the use of
      tertiles specific for this group only slightly increased the odds ratios.
      CONCLUSIONS: : The concentration of CRP, but not fibrinogen nor white blood cells
      is associated with the apoE polymorphism. The activity of the mevalonate pathway
      in the liver may be related to the metabolism of CRP. The predictive value of CRP
      for CAD may be modified by the apoE polymorphism.

PMID- 15571827
TI  - Markers of inflammation in patients with coronary artery disease are also
      associated with glycosylated haemoglobin A1c within the normal range.
AB  - AIMS: Diabetes is a risk factor for atherosclerosis and low-degree inflammation
      may play a central role in both diseases. Glycosylated haemoglobin A(1c)
      (HbA(1c)) is an established measure of long-term glycaemic control but data on
      its correlation with markers of inflammation are limited, especially in patients
      with atherosclerotic manifestations. The aim of the present study was thus to
      investigate the associations between HbA(1c) and a panel of inflammation
      sensitive parameters in patients with and without diabetes. METHODS AND RESULTS:
      This single centre cross-sectional study comprised 314 consecutive subjects who
      underwent coronary angioplasty for stable coronary artery disease. Sixty-six
      patients had diabetes mellitus. Haemoglobin A(1c) and markers of inflammation,
      i.e., plasma levels of CRP, fibrinogen, and albumin, erythrocyte sedimentation
      rate and white blood cell count were measured. All inflammation markers were
      altered in a more inflammatory direction in diabetic patients. Furthermore, when
      non-diabetic patients with HbA(1c) levels within the normal range were studied
      separately, all inflammation-sensitive parameters except albumin correlated
      significantly with HbA(1c). CONCLUSION: In subjects with known coronary
      atherosclerosis, low-degree inflammatory activity is not only increased in
      diabetic patients, but also increased with increasing HbA(1c) in non-diabetic
      individuals with HbA(1c) within the normal range, i.e., at a pre-diabetic level
      of glucose metabolism derangement.

PMID- 15571828
TI  - Use of abciximab prior to primary angioplasty in STEMI results in early
      recanalization of the infarct-related artery and improved myocardial tissue
      reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING
      Study.
AB  - AIMS: The aim of the ReoPro-BRIDGING Austrian multi-centre study was to
      investigate the effects of abciximab (ReoPro) on early reperfusion in ST
      elevation myocardial infarction prior to or during primary percutaneous coronary
      angioplasty (pPCI). METHODS AND RESULTS: Fifty-five patients with STEMI were
      randomized either to start abciximab (0.25 mg/kg bolus followed by 10 microg/min
      infusion) during the organization phase for pPCI (Group 1, n=28) or immediately
      before pPCI (Group 2, n=27). The time between first bolus of abciximab and first
      balloon inflation of pPCI was 83+/-18 vs 21+/-13 min in Group 1 vs 2. The pre
      pPCI ST-segment resolution (55+/-21.4% vs 42.4+/-18.2%, p=0.005), TIMI flow grade
      3 (29% vs 7%, p=0.042), corrected TIMI frame count (58.4+/-32.7 vs 78.9+/-28.4
      frame, p=0.018) %diameter stenosis (76.3 /63.5-100/ vs 100 /73.5-100/; median
      /interquartile range/, p=0.023), were significantly higher in Group 1 vs Group 2.
      Quantitative myocardial dye intensity measurement revealed a significantly higher
      grade of myocardial tissue perfusion (1 /0-9.25/ vs 0 /0-3.0/ grey pixel unit,
      p=0.048) in Group 1 before pPCI. Rapid release of cardiac enzymes was observed in
      Group 1 as compared with Group 2: rate of rise of CK was 210+/-209 vs 97+/-95
      U/l/h (p=0.015). QRS score indicated a smaller infarct size in Group 1 (4.8+/-3.8
      vs 7.6+/-3.5, p=0.011) on day 7. CONCLUSION: The use of abciximab in the
      organization phase for pPCI results in signs of early recanalization of the
      infarct-related artery and a subsequent improved myocardial tissue reperfusion.

PMID- 15571830
TI  - Angiotensin converting enzyme insertion/deletion polymorphism and the risk of
      heart failure in hypertensive subjects.
AB  - AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the
      ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor
      for cardiac hypertrophy and heart failure, especially in hypertensive subjects.
      We assessed the relation between the ACE I/D polymorphism and the risk of
      incident heart failure in normotensive and hypertensive subjects. METHODS AND
      RESULTS: We investigated 4264 normotensive and 2174 hypertensive participants of
      the Rotterdam Study, a population based prospective cohort study. All subjects
      were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart
      failure in normotensive subjects were the same over all genotype strata (10 per
      1000 person-years). In hypertensive subjects, the IR increased with the number of
      D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years).
      Hypertensive subjects carrying the II-genotype did not have an increased risk of
      heart failure compared to normotensive II subjects. However, hypertensive
      subjects carrying one or two copies of the D-allele did have a significantly
      increased risk of heart failure (ID: RR: 1.4 (1.1-1.9) and DD: RR: 1.5 (1.2
      2.1)). CONCLUSION: Our findings suggest that the ACE I/D polymorphism may play a
      modifying role in the development of heart failure in hypertensive subjects.

PMID- 15571829
TI  - Myocardial bridging is associated with alteration in coronary vasoreactivity.
AB  - BACKGROUND: Shear stress alteration has been recognized as a predisposing factor
      for the impairment of endothelial function. Myocardial bridging is a congenital
      condition associated with alteration in shear stress, however, its impact upon
      vasoreactivity remains undetermined. METHODS AND RESULTS: This was a case-control
      designed study with 29 patients with myocardial bridging and 58 patients without
      myocardial bridging. Endothelium-dependent and endothelium-independent changes in
      coronary artery diameters, blood flow and wall shear stress were determined after
      intracoronary infusion of acetylcholine (ACH, 10(-6)-10(-4) mol/L) and
      nitroglycerine (NTG, 200 microg). Coronary flow velocity reserve (CFVR) was
      determined after intracoronary injection of adenosine (18-36 microg). In response
      to ACH, there was more epicardial vasoconstriction at the myocardial bridging
      site compared with the proximal and distal segments (-29.6+/-21.7 vs. -9.6+/-22.5
      and -17.4+/-21.5%, p<0.05) and compared with the control group (-29.6+/-21.7 vs. 
      5.9+/-36.5%, p<0.001). The response to NTG and CFVR was the same in the case and
      the control group. Wall shear rate (WSR) was higher in the MB site at baseline
      and in response to ACH. CONCLUSIONS: MB is characterised by enhanced WSR and
      impairment in endothelium-dependent vasorelaxation. These functional alterations
      may add to the severity of structural lumen compression and thus to the clinical
      presentation of this congenital abnormality.

PMID- 15571831
TI  - Classification and mechanism of Torsade de Pointes initiation in patients with
      congenital long QT syndrome.
AB  - AIMS: To examine the initiating mode of Torsade de Pointes (TdP) in patients with
      congenital long QT syndrome (LQTS). METHODS AND RESULTS: We evaluated 111
      episodes of TdP recorded on the electrocardiograms of 24 patients with congenital
      LQTS, and clarified the initiating mode, the three consecutive preceding RR
      intervals defined as C(2), C(1), and C(0), the timing of initiating premature
      ventricular contraction (PVC) and the cycle length (CL) of TdP. Three different
      initiating patterns were observed: (1) a "short-long-short" sequence (SLS)
      pattern (23 patients, 72 TdP, 65%) defined as one or more short-long cardiac
      cycles followed by an initiating short-coupled PVC (C(1)>C(2) and C(0)), (2) an
      "increased sinus rate" (ISR) pattern (8 patients, 28 TdP, 25%) defined as a
      gradual increase in sinus rate with or without T-wave alternans
      (C(2)>/=C(1)>/=C(0)), and (3) a "changed depolarization" (CD) pattern (5
      patients, 11 TdP, 10%) defined as a sudden long-coupled PVC or fusion beat
      followed by short-coupled PVC. The C(0) was shorter in ISR than SLS and CD (mean
      C(0): 488 vs. 587 and 603 ms, respectively; P<0.05). Therefore, the initiating
      PVC appeared near the T-wave peak of the last beat before onset in ISR, while it
      occurred after the T-wave peak in SLS and CD. The CL of TdP was shorter in ISR
      than in SLS (256 vs. 295 ms, P<0.05). CONCLUSIONS: Our data show the existence of
      three predominant initiating modes of TdP in patients with congenital LQTS and
      suggests a differential mechanism of initiation of TdP for each mode.

PMID- 15571832
TI  - Adenosine restores atrio-venous conduction after apparently successful ostial
      isolation of the pulmonary veins.
AB  - AIMS: Pulmonary vein (PV) isolation is a curative treatment for patients with
      atrial fibrillation. The aim of this study was to evaluate prospectively the
      effects of adenosine administration on the PV activity and atrio-venous
      conduction after PV isolation. METHODS AND RESULTS: Twenty-nine patients (21 m;
      age: 55+/-8 years) were submitted to ostial PV isolation guided by basket
      catheter recordings. After successful isolation, the effects of a 12 mg
      intravenous bolus of adenosine were tested in 62 PVs. In 22/62 PVs (35%), left
      atrium (LA)-to-PV conduction was transiently (16.6+/-7.1 s, range: 3.8-27.9 s) or
      permanently (3 PVs) restored in response to adenosine administration. The
      prevalence of this phenomenon was 39% in left superior PVs, 43% in right superior
      PVs, and 22% in left inferior PVs (p=0.365). It occurred more frequently in the
      presence of dissociated PV activity (11/15 PVs, 73% vs. 11/47 PVs, 23%; p=0.002),
      whereas it was not influenced by the median duration of the radiofrequency
      current (RFC) delivery for each PV [19 (IQR: 12-26) min vs. 16 (IQR: 11-24) min:
      p=0.636]. A lengthening or shortening of the LA-PV conduction time was observed
      at LA-PV conduction appearance and disappearance in 36% and 55% of the cases,
      respectively. Further RFC applications (median: 5.5 min, IQR: 4-11 min) at the
      residual conduction breakthrough(s) indicated by the basket catheter recordings
      definitively eliminated adenosine-induced recovery of LA-PV conduction in all
      cases. Finally, when present, intrinsic PV discharge was invariably depressed by
      adenosine administration. CONCLUSIONS: Adenosine may transiently or permanently
      re-establish LA-PV conduction after apparently successful PV isolation. This
      phenomenon is abolished by additional RFC delivery. However, its possible
      influence on the clinical results of PV ablation must be evaluated by properly
      designed, randomized studies.

PMID- 15571833
TI  - Hotline sessions of the 26th European Congress of Cardiology.

PMID- 15571834
TI  - Drug-eluting stents: meta-analysis in diabetic patients.

PMID- 15571836
TI  - Risk reduction with long-term clopidogrel following percutaneous coronary
      intervention.

PMID- 15571839
TI  - Quantification of peri-operative myocardial infarction after coronary artery
      bypass surgery.

PMID- 15571840
TI  - Myocardial infarction after coronary revascularization: role of cardiovascular
      magnetic resonance oedema imaging.

PMID- 15571841
TI  - Risk of decompression illness among 230 divers in relation to the presence and
      size of patent foramen ovale.

PMID- 15571844
TI  - Prevention of atrial fibrillation after cardioversion: results of the PAFAC
      trial.

PMID- 15571845
TI  - Glucocorticoids, Kounis syndrome and the prevention of atrial fibrillation.

PMID- 15571846
TI  - The UK's National Health Service does not meet its control standards.
AB  - This paper describes some of the difficulties of hospital management and staff in
      meeting the UK National Health Service (NHS) Infection Control Standards designed
      to protect staff and patients against bacterial and viral infections. The
      majority of older hospitals and clinics in the NHS do not have the financial
      resources to provide sterilizing equipment that will meet new acceptable
      standards.

PMID- 15571847
TI  - Considering risks to healthcare workers from glutaraldehyde alternatives in high
      level disinfection.
AB  - Due to concerns over glutaraldehyde's toxicity, two substitutes have recently
      been introduced; ortho-phthalaldehyde (OPA), and a mixture of hydrogen peroxide
      and peracetic acid. There is limited information about the health effects for
      employees from these products. This study assesses the current practices
      regarding the use of high-level disinfectants in British Columbian hospitals and
      predicts the relative toxicities of each product. Industry practices were
      compiled using a comprehensive survey of current practices and decision processes
      in all hospitals in British Columbia. Of 95 hospitals, 64 returned surveys; 80%
      of these used high-level disinfection. Among user hospitals, 49% used
      glutaraldehyde alone and 51% had introduced alternatives. Concern about staff
      health was the most common reason for substituting, but this was frequently not
      considered when choosing specific alternatives. Hospitals that involved
      occupational health, infection control or regional staff in high-level
      disinfectant decisions used glutaraldehyde alternatives less often. In most
      hospitals, it was difficult to find individuals who were knowledgeable about the
      use of disinfectants. Potential health effects associated with each type of high
      level disinfectant were assessed by review of the published literature and
      available manufacturers' data along with qualitative structure-activity
      relationship analysis. Results indicated that although all products irritate the
      skin and respiratory tract, OPA is a potential dermal and respiratory sensitizer
      but hydrogen peroxide and peracetic acid do not cause allergic reactions. Despite
      little being known about the risks to employees from glutaraldehyde alternatives,
      their use is widespread. The potential risks of all high-level disinfectants are
      serious; thus regulators and users are faced with important risk management
      decisions before and after they have been introduced into the workplace.

PMID- 15571848
TI  - An alcohol hand rub containing a synergistic combination of an emollient and
      preservatives: prolonged activity against transient pathogens.
AB  - A new alcohol-based hand antiseptic (Octoxy hand rub) containing a synergistic
      combination of an emollient (Octoxyglycerine) and preservatives was developed and
      evaluated for immediate and prolonged activity against transient bacteria. The in
      vitro and in vivo antimicrobial efficacy was compared with other alcohol hand
      rubs containing preservative/antimicrobial (Prevacare and Avagard). In vitro
      evaluation was carried out using a tube-dilution method and a pig-skin model.
      Rapid and prolonged efficacy in vivo was evaluated against Staphylococcus
      epidermidis on the hands of volunteers. Octoxy hand rub was 100% effective in
      rapidly killing pathogens including methicillin-resistant Staphylococcus aureus
      and vancomycin-resistant Enterococcus faecium in vitro. In volunteers, all three
      hand rubs gave a significant reduction in microbial count within 15s. Octoxy hand
      rub showed significantly higher efficacy against S. aureus and Escherichia coli
      than Avagard and Prevacare 15 min after application to the pig-skin model, and
      against S. epidermidis in both the pig-skin model and in volunteers. Use of
      Octoxy hand rub with broad-spectrum immediate and prolonged antimicrobial
      activity may be a very effective way of improving hand hygiene without exposing
      the hands to higher concentrations of antimicrobials.

PMID- 15571849
TI  - Genomic characterization of oxacillin-resistant Staphylococcus epidermidis and
      Staphylococcus haemolyticus isolated from Brazilian medical centres.
AB  - Studies on the genetic diversity of oxacillin-resistant coagulase-negative
      staphylococcal (CNS) isolates are important for the control and prevention of
      infections. The present study evaluated the clonal diversity of oxacillin
      resistant Staphylococcus epidermidis (ORSE) and Staphylococcus haemolyticus
      (ORSH) strains, isolated from patients in nine Brazilian medical centres by using
      pulsed-field gel electrophoresis (PFGE) after digestion of bacterial DNA using
      SmaI. PFGE analysis of ORSE (N=44) and ORSH (N=25) strains showed the presence of
      29 restriction profiles clustered in 16 PFGE types, and 21 distinct profiles in
      15 PFGE types, respectively, indicating a large genetic diversity among isolates
      of both of these species. Among the ORSE isolates, 23 (52%) strains belonged to
      two predominant PFGE types (named A and B), which were observed in most of the
      hospitals assessed, indicating the spread of these PFGE types in hospitals
      located in Rio de Janeiro. The spread of PFGE types of ORSH was also detected in
      some of the hospitals investigated. The results show that PFGE is a suitable tool
      for epidemiological studies of oxacillin-resistant CNS, and can be used as a
      basis for infection control procedures for these multiresistant organisms.

PMID- 15571850
TI  - Epidemiology of capsular and surface polysaccharide in Staphylococcus aureus
      infections complicated by bacteraemia.
AB  - Staphylococcus aureus is a leading cause of serious hospital- and community
      acquired infections. The discovery of serologically distinct capsular
      polysaccharides on the surface of clinical isolates has allowed the development
      of vaccines and passive protective immunity. We have studied patient
      characteristics, infection characteristics and the surface and capsular
      polysaccharide serotype distribution in patients with S. aureus infections
      complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and
      2000. Nine hundred and ninety-three blood cultures from 331 patients were
      positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had
      end-stage renal failure, and 23% were injection drug users. Forty-two percent of
      infections were caused by methicillin-resistant strains (MRSA), and 60% were
      acquired during hospitalization. Serotyping of the first available isolate per
      patient (N=234 isolates) using polyclonal antibodies showed three major
      phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336
      polysaccharide. MRSA isolates were significantly more likely to be T5 than
      methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5
      MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%,
      P<0.001). This large sample of patients with serious S. aureus infection confirms
      that capsular polysaccharides T5 and T8 cause most human infections, and together
      with serotype 336, account for nearly all those with bacteraemia.

PMID- 15571851
TI  - Costs associated with hospital-acquired bacteraemia in a Belgian hospital.
AB  - Studies from around the world have shown that hospital-acquired infections
      increase the costs of medical care due to prolongation of hospital stay, and
      increased morbidity and mortality. The aim of this study was to determine the
      extra costs associated with hospital-acquired bacteraemias in a Belgian hospital
      in 2001 using administrative databases and, in particular, coded discharge data.
      The incidence was 6.6 per 10000 patient days. Patients with a hospital-acquired
      bacteraemia experienced a significantly longer stay (average 21.1 days, P<0.001),
      a significantly higher mortality (average 32.2%, P<0.01), and cost significantly
      more (average 12853 euro, P<0.001) than similar patients without bacteraemia. At
      present, the Belgian healthcare system covers most extra costs; however, in the
      future, these outcomes of hospital-acquired bacteraemia will not be funded and
      prevention will be a major concern for hospital management.

PMID- 15571852
TI  - Hospital-based allogenic bone bank--10-year experience.
AB  - Bone banking in a hospital provides resources of allogenic bone grafts. However,
      they may transmit infection from donor to recipient. We found few reports
      discussing the infection rate and monitoring processes associated with bone
      banks. The discard rate using the screening test was 18.5% (309/1674) in this
      series. The leading cause was hepatitis B antigen (HBsAg) positive donor serum
      (67%), followed by Venereal Disease Research Laboratory (VDRL) positive donor
      serum (15%), and anti-hepatitis C virus (HCV) positive donor serum (12%). The
      overall infection rate in the recipients was 1.3% (17/1365). Among 1353 implanted
      allografts, 22 cases (1.6%) had a positive swab culture result after thawing.
      Only four out of these 22 cases (18.2%) developed infection. However, the wound
      cultures of the infected recipients were different from the swab culture of
      thawing allografts except in one case. Among the 1331 recipients with sterile
      allograft bones, 13 (1%) were found to have infection. In conclusion, our bone
      bank operates under a strict monitoring system which results in a low infection
      rate. The recipient's status, the aseptic technique and environment during
      operation is likely to be more critical in prevention of allograft-related
      infection.

PMID- 15571853
TI  - Nosocomial bloodstream infections with Burkholderia stabilis.
AB  - Burkholderia stabilis was grown from blood cultures of seven patients presenting
      with signs and symptoms of septicaemia in the intensive care unit at Mersin
      University Hospital, Mersin, Turkey between July and October 2002. Four patients
      had one B. stabilis-positive blood culture, two patients had two, and one patient
      had four. Isolates from six of seven patients had the same resistotype and random
      amplified polymorphic DNA analysis type. Despite treatment with ciprofloxacin and
      imipenem, to which the strains were susceptible, all patients died one to eight
      days after isolation of B. stabilis from their blood. B. stabilis should be
      regarded as an opportunistic pathogen that may cause nosocomial bloodstream
      infections.

PMID- 15571854
TI  - Evaluation of antibiotic use in intensive care units of a tertiary care hospital
      in Turkey.
AB  - The object of this study was to evaluate the appropriateness of antibiotic use in
      relation to diagnosis and bacteriological findings in the intensive care units
      (ICUs) of a 1100-bed referral and tertiary care hospital with an antibiotic
      restriction policy in Turkey. Between June and December 2002, patients who
      received antibiotics in the medical and surgical ICUs were evaluated
      prospectively. Two infectious diseases (ID) specialists assessed the antibiotics
      ordered daily. Of the 368 patients admitted to the ICUs, 223 (60.6%) received 440
      antibiotics. The most frequently prescribed antibiotics were first-generation
      cephalosporins (16.1%), third-generation cephalosporins (15.2%), aminoglycosides
      (12.1%), carbapenems (10.7%) and ampicillin-sulbactam (8.7%). Antibiotic use was
      inappropriate in 47.3% of antibiotics. ID specialists recommended the use of 47%
      of all antibiotics. An antibiotic order without an ID consultation was more
      likely to be inappropriate [odds ratio (OR)=13.2, P<0.001, confidence intervals
      (CI)=4.4-39.5]. Antibiotics ordered empirically were found to be less appropriate
      than those ordered with evidence of culture and susceptibility results (OR=3.8,
      P=0.038, CI=1.1-13.1). Inappropriate antibiotic use was significantly higher in
      patients who had surgical interventions (OR=3.6, P=0.025, CI=1.2-10.8).
      Irrational antibiotic use was high for unrestricted antibiotics. In particular,
      antibiotic use was inappropriate in surgical ICUs. Additional interventions such
      as postgraduate training programmes and elaboration of local guidelines could be
      beneficial.

PMID- 15571855
TI  - Mycobactericidal and tuberculocidal activity of Korsolex AF, an amine
      detergent/disinfectant product.
AB  - The mycobactericidal and tuberculocidal activities of Korsolex AF against
      Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare
      (MAI), Mycobacterium kansasii and Mycobacterium chelonae were determined using
      quantitative suspension and carrier tests. The effects of organic load and hard
      water were also considered. A clinical isolate of MAI was the most resistant of
      the four test organisms. A 2% solution had good mycobactericidal and
      tuberculocidal activities after 30 min of exposure. Although further evaluation
      using European standard tests is necessary, we conclude that Korsolex AF appears
      to be a promising product for the disinfection of hospital instruments
      contaminated with mycobacteria.

PMID- 15571856
TI  - Risk of re-introduction of methicillin-resistant Staphylococcus aureus into the
      hospital by intrafamilial spread from and to healthcare workers.

PMID- 15571857
TI  - Serratia marcescens outbreak in a neonatal intensive care unit prompting review
      of decontamination of laryngoscopes.

PMID- 15571858
TI  - Epidemiological characteristics of nosocomial bacteraemias among ICU and non-ICU
      patients in a tertiary-care hospital in Greece.

PMID- 15571859
TI  - Nebulizer decontamination.

PMID- 15571860
TI  - Mycoplasma pneumoniae: a rarely diagnosed agent in ventilator-acquired pneumonia.

PMID- 15571861
TI  - Monopercitric acid--a new disinfectant with excellent activity towards
      clostridial spores.

PMID- 15571862
TI  - 4-Anilinoquinazolines with Lavendustin A subunit as inhibitors of epidermal
      growth factor receptor tyrosine kinase: syntheses, chemical and pharmacological
      properties.
AB  - 4-Anilinoquinazoline derivatives are widely investigated due to their potent
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. Two
      4-anilinoquinazolines with Lavendustin A subunit (10a,b) were synthesized and
      examined for their EGFR tyrosine kinase inhibitory activity as well as their
      antiproliferative properties on variant human cancer cell lines. Both compounds
      maintained their EGFR tyrosine kinase inhibitory activity at the 10-7 M level and
      led to significant growth inhibition in certain leukemia, non-small cell lung
      cancer (NSCLC), ovarian cancer, renal cancer and breast cancer cell lines with
      GI50 values at the 10-6 M level. There could not be observed any notable
      difference between 10a and 10b regarding to their antiproliferative activity.
      Interestingly, we observed the high tendency of 10a and 10b to include certain
      solvents, e.g. water, DMF, DMSO, which may be due to the remarkable number of
      hydrogen accepting/donating groups in 10a and b. An X-ray analysis of 10a
      including water and DMF illustrates a possible hydrogen bond pattern and could
      serve as information for preferred receptor (e.g. EGFR tyrosine kinase) binding
      sites. Finally, we aimed for irreversible EGFR tyrosine kinase inhibitors. The p
      quinone derivatives 11a and 11b, which contain a Michael acceptor position
      according to the irreversible inhibitor CI-1033, could be derived from the p
      hydroquinone derivatives 10a or 10b, respectively, by oxidation. However, due to
      their instability 11a and 11b could not be obtained in a pure form.

PMID- 15571863
TI  - Synthesis and evaluation of in vivo activity of diphenylhydantoin basic
      derivatives.
AB  - During the search for antiarrhythmic agents among amide derivatives of phenytoin,
      compound 7 {3-ethyl-1-[2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-2,4-dioxo
      5,5-diphenyl-imidazolidine} was selected as it showed antiarrhythmic as well as
      antihypertensive activity. Treating this compound as a lead, new derivatives 8-19
      were synthesised, differing in piperazine phenyl ring substitution (2-, 3-, 4-Cl,
      2-CH3O) as well as in hydantoin N3 alkyl chain (ethyl, ethyl acetate or ethyl 2
      propionate). The obtained compounds in form of hydrochlorides 7a-19a were
      examined for prophylactic antiarrhythmic and antihypertensive properties.
      Compounds containing ethyl 2-propionate moiety (17a, 18a) exhibited the highest
      antihypertensive properties. Water-soluble compounds, containing 2
      methoxyphenylpiperazine group (11a, 19a), showed strong antiarrhythmic properties
      in adrenaline-induced arrhythmia; compound 9a {1-[3-(4-(3-chloro-phenyl)
      piperazin-1-yl)- 2-hydroxy-propyl]- 3-ethyl-2,4-dioxo-5,5-diphenyl-imidazolidine
      hydrochloride} exhibited the highest antiarrhythmic activity in barium chloride
      arrhythmia model.

PMID- 15571864
TI  - Synthesis of 9-acridinyl sulfur derivatives: sulfides, sulfoxides and sulfones.
      Comparison of their activity on tumour cells.
AB  - The synthesis of several acridine thioethers is described. These compounds were
      oxidized to give new sulfoxides and sulfones. Among 23 compounds prepared, 19
      were tested in vitro against the human cancer cell lines panel of NCI screening.
      Activity is increased 5-10 times from sulfides to sulfoxides. Among substituted
      groups in the side chain, sulfur mustard, epoxy sulfide and sulfoxide displayed
      the most interesting activity.

PMID- 15571865
TI  - Structure-activity relationships of sandalwood odorants: synthesis and odor of
      tricyclo beta-santalol.
AB  - In a series of structure-odor relationship investigations the synthesis of a new
      tricyclic beta-santalol derivative is described. The product of a multistep
      synthesis appears in an olfactive evaluation more or less odorless, may be
      slightly creamy but definitely with no sandalwood odor. This modification with a
      bulky aliphatic bridge in the neighborhood of the quaternary C3-atom demonstrated
      the sensitivity of sandalwood odor on the structure of beta-santalol analogues.

PMID- 15571866
TI  - A new synthetic approach of N-(4-amino-2-methylquinolin-6-yl)-2-(4
      ethylphenoxymethyl)benzamide (JTC-801) and its analogues and their
      pharmacological evaluation as nociceptin receptor (NOP) antagonists.
AB  - A series of 4-amino-2-methylquinoline and 4-aminoquinazoline derivatives,
      including the reference NOP antagonist JTC-801, were synthesized by an
      alternative pathway and their in vitro pharmacological properties were
      investigated. 3-Substitution of the quinoline ring resulted very critical for
      affinity. So 3-methyl derivative 4j showed a similar potency compared with the
      reference 4h while bulky lipophilic or electron withdrawing groups in the same
      position strongly decreased affinity. Structural and conformational requirements
      for affinity were outlined by NOE NMR and computational methods and suggestions
      for a pharmacophore model design were provided.

PMID- 15571867
TI  - Synthesis, antitumour and antimicrobial activities of new peptidyl derivatives
      containing the 1,3-benzodioxole system.
AB  - Two series of 5 and 6-substituted 1,3-benzodioxole peptidyl derivatives were
      synthesized and evaluated as antitumour and antimicrobial agents. The compounds
      that could be conveniently prepared in a few steps processes from natural safrole
      have been characterised by IR and 1H-NMR spectroscopy. In vivo antitumor activity
      tests showed that some of the compounds were able to inhibit carcinoma S-180
      tumour growth in mice. The in vitro antimicrobial activity of all compounds
      revealed that they are able to promote the growth of some organisms, including
      Bacillus subtilis.

PMID- 15571868
TI  - Synthesis and antifungal activity of cholesterol-hydrazone derivatives.
AB  - A series of hydrazones synthesized from various cholesterol derivatives were
      evaluated for their in vitro antimicrobial properties against human pathogens.
      The activity was highly dependent on the structure of the different compounds
      involved. The best results have been obtained with tosylhydrazone cholesterol
      derivatives 8 and 9 exhibiting activities against Candida albicans (CIP 1663-80)
      at a concentration of 1.5 microg/ml.

PMID- 15571869
TI  - Organoiodine (III) mediated synthesis of 3-aryl/hetryl-5,7-dimethyl-1,2,4
      triazolo[4,3-a]pyrimidines as antibacterial agents.
AB  - Synthesis of some new 3-aryl/hetryl-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidines
      (3a-k) has been accomplished by the oxidation of 4,6-dimethyl-2
      pyrimidinylhydrazones of various aldehydes with iodobenzene diacetate in
      dichloromethane. Nine new compounds (3b-g and 3i-k) were tested in vitro for
      their antibacterial activity. Two compounds, namely 3-(4'-pyridyl)-5,7-dimethyl
      1,2,4-triazolo[4,3-a]pyrimidine (3k) and 3-(3',4'-dimethoxyphenyl)-5,7-dimethyl
      1,2,4-triazolo[4,3-a]pyrimidine (3f), were associated with substantially higher
      antibacterial activity than some commercial antibiotics against Bacillus
      subtilis, Escherichia coli, Staphylococcus aureus and Salmonella typhi at MIC
      (minimum inhibitory concentration) i.e. 10 microg/ml.

PMID- 15571870
TI  - Structural variations of piritrexim, a lipophilic inhibitor of human
      dihydrofolate reductase: synthesis, antitumor activity and molecular modeling
      investigations.
AB  - Piritrexim (PTX) (1), a lipophilic inhibitor of the human dihydrofolate
      reductase, has been evaluated as an anticancer agent. The synthesis of four
      structural variations (2-5) of PTX is reported. The PTX analogues 2-5 were
      obtained by reaction of suitable C3-building blocks with pyrimidine-2,4,6
      triamine (14) or with cyanacetamide (7) and guanidine (10). The evaluation of 2-4
      for antitumor activity against a panel of 60 human cancer cell lines showed
      inhibitory effects on the growth of the cell lines. These data are supported by
      molecular modeling and docking studies, which show that compounds 2-4 share the
      same binding mode within the DHFR active site. Moreover, the estimated ligand
      binding energies are in good agreement with the experimental activity data.

PMID- 15571871
TI  - Some pyrrole substituted aryl pyridazinone and phthalazinone derivatives and
      their antihypertensive activities.
AB  - In this work, some 2-nonsubstituted/2-methyl-/2-(2-acetyloxyethyl)-6-[4
      (substituted pyrrol-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone, derivatives and
      2-nonsubstituted/2-methyl- 4-[4-(substituted pyrrol-1-yl)phenyl]-1(2H)
      phthalazinone derivatives were synthesised by reacting hexan-2,5-dion or 1-aryl-3
      carbethoxypent-1,4-diones with corresponding 2-substituted/nonsubstituted 6-(4'
      aminophenyl)-4,5-dihydro-3(2H)-pyridazinone or 2-substituted/nonsubstituted-4-(4'
      aminophenyl)-(2H)-phthalazinone under Paal-Knorr pyrrole synthesis conditions.
      The antihypertensive activities of the compounds were examined both in vitro and
      in vivo. Some pyridazinone derivatives showed appreciable activity.

PMID- 15571872
TI  - Low dose beta-emitter source induces sexual reproduction instead of fragmentation
      in an earthworm, Enchytraeus japonensis.
AB  - We examined whether background radiation, or radiation at a slightly higher
      level, plays a role in the reproduction of a terrestrial earthworm. Enchytraeus
      japonensis a recently described terrestrial oligochaete, reproduces asexually by
      fragmentation and subsequent regeneration. Following radiation exposure in which
      the worms were subjected to a 32P beta-emitter source at 15 times the background
      dose rate (4.5 microGy/h), a statistically significant decrease in the number of
      fragmentations was observed as compared with the sham controls. At that time, in
      a stained preparation with haematoxylin and eosin (HE), sexual reproduction
      occurred instead of asexual fragmentation, and mature oocytes were observed in
      the body of grown worms. However, increasing the radiation dose rate by 30
      microGy/h resulted in the complete disappearance of the radiation-induced
      effects, i.e., fragmentation again occurred after 14 h. The results of this study
      indicate that a lower dose of radiation may be essential to achieve sexual
      reproduction, inducing an inhibition of fragmentation (asexual reproduction), but
      at higher, more cytotoxic doses of radiation these effects are negated.

PMID- 15571873
TI  - Analysis of the individual health benefits accruing from a domestic radon
      remediation programme.
AB  - Although radon can be present within buildings at sufficient levels to pose a
      health risk, levels can be reduced relatively easily. Recent studies on a group
      of radon-remediated homes, based on assessment of collective population-average
      risk coefficients, have estimated the benefits and cost effectiveness accruing
      from remediation and have confirmed that domestic remediation in UK radon
      Affected Areas would result in significantly reduced cancer risks to the
      population in those areas. Although the population-average approach used hitherto
      has applied occupancy and lung-cancer risk factors, these are potentially
      misleading in assessing discrete populations. The study reported here uses the
      recently developed European Community Radon Software (ECRS) to quantify
      individual risks in a sample of householders who remediated their homes following
      indications that radon levels exceeded the action level. The study proceeds from
      population-averaged to 'individual risk' evaluation, successfully comparing
      individual and collective risk assessments, and demonstrates that those who
      remediate are not representative of the general population. Health benefits
      accruing from remediation are three times lower than expected, largely because
      remediators are older, live in smaller households, and smoke less than the
      population average, leading to the conclusion that the current strategy employed
      in the UK is failing to target those most at risk.

PMID- 15571874
TI  - Mitigation of a radon-rich Belgian dwelling using active subslab
      depressurization.
AB  - In a radon prone area in Belgium, a dwelling with high indoor radon
      concentrations was identified through a passive measurement. Next, a continuous,
      active radon monitoring device was installed for one month. A 20-a retrospective
      radon assessment was also performed. The house was subsequently mitigated through
      active subslab depressurization with a radial fan. Afterwards the dwelling was
      actively monitored for several more months to observe the effects of the
      mitigation and to study the effect of reducing the fan power. Dose evaluations
      were made to evaluate the health benefit of the mitigation. It was seen that the
      results of the three measuring techniques before mitigation all yielded between
      1700 and 2000 Bq/m3. Clear diurnal radon variations showed up only after
      mitigation. After mitigation, the average radon concentration fell to less than
      200 Bq/m3. The yearly average dose was reduced from potentially 45 mSv/y to less
      than 4.5 mSv/y through mitigation. Reducing fan power to 50% did not clearly
      influence the amount of radon entering into the dwelling.

PMID- 15571875
TI  - Radiocaesium fallout behaviour in volcanic soils in Iceland.
AB  - The retention of 137Cs in various types of Andosols in Iceland was investigated.
      Soils were sampled at 29 sites with varying precipitation and environmental
      conditions. Samples were obtained from 0 to 5, 5 to 10, and 10 to 15 cm depths.
      The amount of radiocaesium present was quite variable, ranging between 300 and
      4800 Bq m(-2) and correlated closely to total annual precipitation (r2=0.71). The
      majority of 137Cs, 82.7% on average, was retained in the uppermost 5 cm of the
      soil. The greatest penetration of 137Cs was observed for organic Histosols (76.3%
      in top 5 cm). The Icelandic Vitrisols (barren, poorly developed Andosols) are
      coarse grained with only 2-5% clay content and contain little organic matter
      (<1%). Yet these soils retained 74% of 137Cs in the top 5 cm. The results
      indicate that radiocaesium fallout is strongly retained by colloidal materials
      characteristic of Andosols, such as allophane and ferrihydrite. Most soils in
      Iceland are subject to severe and prolonged freezing and waterlogging; despite
      this, 137Cs is retained in the upper soil horizons and vertical migration is
      negligible in Icelandic Andosols. However, erosion and aeolian activity can
      markedly influence the amount and vertical distribution of radiocaesium in
      Icelandic soils.

PMID- 15571876
TI  - Derivation of ecotoxicity thresholds for uranium.
AB  - Assessment of the risk of impact from most radionuclides is based on the total
      radiological dose rate to the organism of concern. However, for uranium (U) there
      can be greater risk from chemical toxicity than radiological toxicity (depending
      on the isotopic composition). Chemical ecotoxicity of U is dependent on several
      environmental parameters. The most important are carbonate content, because of
      the formation of soluble carbonate complexes, and divalent cation content (Ca++
      and Mg++), because of their competitive interaction with the uranyl ion (UO2++).
      This study summarizes the literature available to set PNECs (predicted no-effect
      concentrations) for chemical toxicity of U to non-human biota. The corresponding
      radiological doses were estimated, and as expected chemical toxicity proved to be
      the greater concern. There were limited data from some types of biota; however,
      PNECs for the types of biota of interest were as follows: terrestrial plants--250
      mg U kg(-1) dry soil; other soil biota--100 mg U kg(-1) dry soil; freshwater
      plants--0.005 mg U L(-1) water; freshwater invertebrates--0.005 mg U L(-1) water;
      freshwater benthos--100 mg U kg(-1) dry sediment; freshwater fish at water
      hardnesses of: <10 mg CaCO3 L(-1) (very soft water)--0.4 mg U L(-1) water; 10-100
      mg CaCO3 L(-1) (soft water)--2.8 mg U L(-1) water; and >100 mg CaCO3 L(-1) (hard
      water)--23 mg U L(-1) water; or as a function of hardness--0.26 (hardness as mg
      CaCO3 L(-1); mammals--0.1 mg U kg(-1) body weight d(-1).

PMID- 15571877
TI  - Radon and thoron monitoring in the environment of Kumaun Himalayas: survey and
      outcomes.
AB  - Monitoring of radon, thoron and their daughter products was carried out in houses
      of Kumaun Himalaya, India using LR-115 plastic track detectors. The measurements
      were made in residential houses from June 1999 to May 2000 at a height of 2.5 m
      from ground level using a twin chamber radon dosimeter. The twin chamber radon
      dosimeter can record the values of radon, thoron and their decay products
      separately. Maximum and minimum indoor radon and thoron concentrations were
      evaluated and activity concentrations of radon and thoron daughters were
      estimated. The resulting dose rates due to radon, thoron and their decay products
      varied from 0.04 to 1.89 microSv/h. A detailed analysis of the distribution of
      radon, thoron and their decay products inside the house is also reported. The
      observed dose rates inside the houses of Kumaun Himalaya were found to be lower
      than the ICRP recommended value of 200 Bq/m3 and thus are within safe limits.

PMID- 15571878
TI  - What should be included in a methods section?

PMID- 15571879
TI  - An explorative study of Sudanese midwives' motives, perceptions and experiences
      of re-infibulation after birth.
AB  - OBJECTIVE: to explore Sudanese midwives' motives for and perceptions and
      experiences of re-infibulation after birth and to elucidate its context and
      determinants. DESIGN: triangulation of methods, using observational techniques
      and open-ended interviews. SETTING AND PARTICIPANTS: two government hospitals in
      Khartoum/Omdurman, Sudan, for the observations and in-depth interviews with 17
      midwives. FINDINGS: midwives are among the major stakeholders in the performance
      of primary female genital cutting (FGC) as well as re-infibulation. Focusing on
      re-infibulation after birth, midwives were trying to satisfy differing, and
      sometimes contradictory, perspectives. The practice of re-infibulation (El Adel)
      represented a considerable source of income for the midwives. The midwives
      integrated the practice of re-infibulation into a greater whole of doing well for
      the woman, through an endeavour to increase her value by helping her to maintain
      her marriage as well as striving for beautification and completion. They were
      also trying to meet socio-cultural requests, dealing with pressure from the
      family while balancing on the edge of the law. KEY CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: the findings confirm that midwives are important stakeholders in
      perpetuating re-infibulation, and indicate that the motives are more complex than
      being only economic. The constant balancing between demands from others puts the
      midwives in a difficult position. Midwives' potential role to influence views in
      the preventative work against FGC and re-infibulation should be acknowledged in
      further abolition efforts.

PMID- 15571880
TI  - Support from a prenatal instructor during childbirth is associated with reduced
      rates of caesarean section in a Mexican study.
AB  - OBJECTIVE: to assess the association between non-clinical factors and the
      incidence of caesarean section (CS); to estimate the effect of a prenatal
      instructor's presence during childbirth on birth outcome (vaginal or CS). DESIGN:
      cross-sectional study from a register of women who attended prenatal classes.
      Multivariate logistic regression was used to measure the effects of each variable
      on whether the birth was vaginal or CS. SETTING: Mexico City, Mexico.
      PARTICIPANTS: 992 births to 847 women from the register of the Birth Education
      Centre (CEPAPAR) between 1987 and 2000. FINDINGS: the incidence of CS was 33%.
      The most commonly reported (by the women) reason for performing a CS was dystocia
      (53%). Most women were middle or upper-middle class professionals, and 85% of the
      women gave birth in private institutions. Odds of having a CS were higher among
      women who gave birth in a large hospital, women who were over 25 years of age,
      primigravidae, and women who were not supported by a prenatal instructor during
      childbirth. CONCLUSIONS: non-clinical factors considerably affect the type of
      birth outcome (vaginal vs. CS). A system in which a prenatal instructor provided
      support to the woman during childbirth could contribute significantly to reducing
      initial and repeat CS.

PMID- 15571881
TI  - An exploration of midwives' views of the current system of maternity care in
      England.
AB  - OBJECTIVE: to explore, in-depth, the views of midwives working in maternity
      services about birth setting, models of care and philosophy of care. DESIGN: an
      Appreciative Inquiry approach was adopted utilising focus group interviews as the
      method of data collection. SETTING: 15 focus group interviews were conducted at
      14 sites in England. PARTICIPANTS: a purposive sample of 120 midwives and six
      student midwives who were serving women in different birth settings (home, free
      standing maternity units, midwife-led units, and traditional obstetric units)
      participated, in 2001/2002. FINDINGS: the main themes generated by the midwives
      were: cultural changes; midwifery leadership; appropriate role models; training
      in normality; appropriate responsibility of care divisions; choice for women;
      equity of care provision between women considered to be at high or low risk; and
      staff morale. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this study
      highlighted the consistency of views amongst midwives working in different
      settings. Midwives wanted support to practice autonomously in an environment that
      facilitated equity of care for women and job satisfaction for midwives.
      Suggestions were put forward by midwives on how to improve maternity services. A
      unified approach is required to develop these suggestions into strategies, that
      will remove the identified barriers and promote normality.

PMID- 15571882
TI  - A qualitative study of mothers' and fathers' experiences of routine ultrasound
      examination in Sweden.
AB  - OBJECTIVE: to conceptualise mothers' and fathers' thoughts and feelings before,
      during and after the routine ultrasound examination during the second trimester
      of pregnancy. DESIGN, SETTING AND PARTICIPANTS: a grounded theory study. Two to
      four weeks after their ultrasound examination, 22 Swedish mothers and 22 fathers
      were interviewed in their homes. FINDINGS: the basic social process was
      confirmation of a new life. The four categories, visualising-the evident option,
      overwhelming to see life; becoming a family and reassuring, all represent a time
      span in the parents' process towards confirmation of a new life. The caregivers'
      way of assisting and supporting the process by information and treatment was very
      important to parents. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: as the
      ultrasound examination is perceived as a confirmation of a new life it is an
      extremely important milestone for both parents so the father should be encouraged
      to participate. It is an important and unique event for both women and men in
      their process towards becoming parents. This process was largely dependent on the
      treatment the parents had received during the examination and the information
      given. The findings of this study are of interest to midwives and others who
      perform ultrasound examinations as it explains why adequate time must be allowed
      for the examination and the importance of the information given before hand. When
      introducing new forms of fetal diagnosis in the future it should be kept in mind
      that this might irrevocably be accepted by parents who long for confirmation of a
      new life.

PMID- 15571883
TI  - A survey of regional guidelines for intrapartum electronic fetal monitoring in
      women at low obstetric risk.
AB  - AIM: to determine whether intrapartum fetal monitoring guidelines used by
      midwives in one region of England for women at low risk of obstetric
      complications were evidence-based. OBJECTIVE: to assess the quality of such
      guidelines using an appraisal tool. DESIGN AND SETTING: an appraisal of
      guidelines gained via a postal survey of all National Health Service Trusts
      supplying maternity services in one region in the north of England, conducted
      over a six-week period (June-July 2001). PARTICIPANTS: 28 Trusts were eligible to
      participate; 32 guidelines were returned from 24 Trusts. DATA ANALYSIS: two
      reviewers from a multi-disciplinary panel appraised each guideline, producing two
      sets of data that were analysed independently of each other. Each was treated as
      a separate case (n=64 cases). Inter-reviewer agreement was summarised using
      descriptive categories. FINDINGS: the highest possible overall quality score was
      54, and the lowest 18. Whilst no guideline scored 54, five of the 64 cases scored
      18. The mean overall quality score was 26.8. In 36 of the 64 cases, both
      reviewers rated guidelines as 'definitely not' recommended for practice.
      Guidelines were scored against specific aspects of evidence-based practice. Forty
      one of the 64 cases received the lowest possible quality score (='1') for use of
      systematic reviews of the literature on electronic fetal monitoring. In 47 cases,
      guidelines were scored '1' for the quality of evidence-based clinical
      recommendations. The quality of information on client monitoring preferences was
      considered low in over half the 64 cases (n=35). There were no instances where
      the number of cases receiving 'highest possible quality' scores was greater than
      those receiving 'lowest possible quality' ratings. CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: a small number of guidelines were assessed as high quality, but the
      majority were poorly appraised by the reviewer group in most areas. This has
      implications for the delivery of evidence-based midwifery care since those
      midwives practising according to the guidelines surveyed would not have been
      supported in implementing research into practice.

PMID- 15571884
TI  - Interprofessional education in a midwifery curriculum: the learning through the
      exploration of the professional task project (LEAPT).
AB  - OBJECTIVE: to develop interprofessional education for students of midwifery,
      nursing and medicine. To foster collaborative working and learning between
      students of midwifery, nursing and medicine. DESIGN: a quasi-experimental method
      to evaluate the outcomes of an intervention (a problem-based learning (PBL)
      scenario) with interprofessional students and facilitators. Data were collected
      using pre- and post-test questionnaires. SETTING: a University and National
      Health Service healthcare facilities in the North of England. PARTICIPANTS: 40
      students of midwifery, nursing and medicine. FINDINGS: student midwives
      participating in the PBL scenario in this interprofessional format improved their
      attitudes to working in this environment. All students enjoyed the opportunity to
      learn in an interprofessional team, and they felt that the experience provided a
      safe environment to help prepare for their future roles. The learning opportunity
      enabled all students to reflect on each other's role and to discuss differing
      perspectives of care, although the student midwives had mixed feelings about the
      PBL experience. IMPLICATIONS FOR PRACTICE: interprofessional learning using PBL
      is a useful environment for students to learn about each others' role, and to
      prepare for working together as qualified professionals in a collaborative
      manner. However, time and commitment is required to plan joint working in order
      to maximise the benefits.

PMID- 15571885
TI  - A feasibility study of an intervention to enhance family support for breast
      feeding in a deprived area in Bristol, UK.
AB  - OBJECTIVE: to assess fathers' and grandmothers' knowledge of breast feeding and
      their ability to support successful breast feeding. To design a suitable
      intervention for fathers and grandmothers to support breast-feeding mothers, to
      assess the acceptability and feasibility of the intervention and monitor its
      likely effects on breast-feeding rates. DESIGN: qualitative focus groups and
      interviews. Evaluation of the feasibility of an antenatal intervention. SETTING:
      Community Health Centre and family homes in an area of relative social and
      economic deprivation in South Bristol, UK, from November 2001 to May 2003.
      PARTICIPANTS: 10 grandmothers and five fathers in focus groups and interviews.
      Twenty-nine families in the intervention. INTERVENTION: an antenatal intervention
      for grandmothers or partners to support breast feeding, which combined the
      benefits and mechanics of breast feeding with ways of providing support for
      breast feeding. FINDINGS: using an antenatal session based around a leaflet,
      specifically written for grandmothers and partners, and including a demonstration
      of good breast-feeding positioning and attachment in addition to the discussion
      of specific issues around the health benefits and mechanics of breast feeding was
      found to be acceptable, useful and enjoyable by all participants, particularly
      for first-time parents. The importance of fathers and grandmothers in providing
      emotional and practical support for breast-feeding mothers is highlighted, since
      those who were still breast feeding at eight weeks all felt that they were
      receiving similar or better support postnatally than they were antenatally.
      Significantly more intervention mothers were breast feeding their babies at eight
      weeks than in the wider practice population of mothers outside the study who
      intended to breast feed. Fathers' attitudes to breast feeding postnatally were
      fairly similar to those before the baby was born with breast feeding in public
      and knowing how much milk the baby was getting having the most influence on
      whether they felt that their partner should continue to breast feed. IMPLICATIONS
      FOR PRACTICE: this type of intervention could be part of a multi-faceted approach
      towards improving breast-feeding initiation and continuation, particularly in
      areas of low prevalence. Health professionals should be opportunistic about
      involving other family members in discussions about breast feeding whenever
      possible, both antenatally and postnatally.

PMID- 15571886
TI  - Systematic review of sexual risk among pregnant and mothering teens in the USA:
      pregnancy as an opportunity for integrated prevention of STD and repeat
      pregnancy.
AB  - Behaviors that lead to teen pregnancy also place young women at risk for STDs and
      repeat pregnancy. Compared to the broad literature on adolescent sexual risk
      behavior, our understanding of sexual risk in pregnant/mothering teens lags far
      behind. Primary objectives of this systematic review (1981-2003) of
      pregnant/mothering teens were to: (1) document rates of STD, repeat pregnancy,
      condom use, and contraception; (2) identify correlates of these biological and
      behavioral outcomes; (3) review sexual risk reduction interventions; and (4)
      discuss directions for future research and implications for clinical care. Fifty
      one studies met inclusion criteria. Rates of STD and repeat pregnancy were high,
      with the majority of teens engaging in unprotected sex during and after
      pregnancy. An Ecological Model of Sexual Risk, based on Bronfenbrenner's (1989)
      Ecological Systems Theory, was proposed to organize findings on correlates of
      sexual risk. Improvements in research, including integration of outcomes and risk
      factors, stronger methodologies, and standardized assessments, are essential.
      Results suggest that teen pregnancy is a marker for future sexual risk behavior
      and adverse outcomes, and that pregnant/mothering teens need hybrid interventions
      promoting dual use of condoms and hormonal contraception. Pregnancy may provide a
      critical "window of opportunity" for sexual risk reduction.

PMID- 15571887
TI  - Factors associated with forced sex among women accessing health services in rural
      Haiti: implications for the prevention of HIV infection and other sexually
      transmitted diseases.
AB  - The goals of the current study were to: (1) estimate the prevalence of forced sex
      among women accessing services at a women's health clinic in rural Haiti; and (2)
      examine factors associated with forced sex in this population. Based on data from
      a case-control study of risk factors for sexually transmitted diseases (STDs), a
      cross-sectional analysis to examine factors associated with forced sex was
      performed. A number of factors related to gender inequality/socioeconomic
      vulnerability placed women in rural Haiti at higher risk of forced sex. The
      strongest factors associated with forced sex in multivariate analyses were: age,
      length of time in a relationship, occupation of the woman's partner, STD-related
      symptoms, and factors demonstrating economic vulnerability. The findings suggest
      that prevention efforts must go beyond provision of information and education to
      the pursuit of broader initiatives at both local and national levels. At the
      community level, policy-makers should consider advancing economic opportunities
      for women who are vulnerable to forced sex. Improving access to community-based
      income-generating activities may begin to address this problem. However, the
      viability of these local projects depends largely upon Haiti's 'macro-economic'
      situation. In order to ensure the success of local initiatives, external
      humanitarian and development assistance to Haiti should be supported. By
      broadening the definition of "prevention" interventions, we may begin to address
      the systemic problems that contribute to the occurrence of forced sex and the
      increasing incidence of HIV infection throughout the world, such as gender
      inequality and economic vulnerability. Taking into account factors influencing
      risk at the local level as well as the macro-level will potentially improve our
      capacity to reduce the risk of forced sex and the spread of STDs, including HIV
      infection, for millions of women living in poverty worldwide.

PMID- 15571888
TI  - Indigenous representations of illness and AIDS in Sub-Saharan Africa.
AB  - Cultures all over the world have evolved illness representations that can
      accommodate not only new diseases, but also new epistemologies for explaining
      disease. This paper examines illness representations in Sub-Saharan Africa, and
      how these have responded to the emergence of AIDS. Indigenous views of illness
      (particularly STDs) exhibit coherent structure, in which causation, prevention
      and treatment relate to one another in functional ways. As an STD, an epidemic,
      and a disease which leads to premature death, AIDS lends itself readily to
      accommodation into established indigenous representations of illness. Even
      biomedical views of causation can be readily incorporated into traditional views
      of how illnesses are caused. However, biomedical and traditional views concerning
      prevention appear to be in direct conflict with one another, with potentially
      hazardous consequences. Research exploring the extent to which indigenous beliefs
      may be influencing people's decisions about safe sex could offer useful insights
      for AIDS prevention programs.

PMID- 15571889
TI  - Domestic violence, sexual ownership, and HIV risk in women in the American deep
      south.
AB  - Domestic violence and sexual abuse are important correlates of HIV risk in women.
      This paper examines the links between HIV risk and domestic violence in women in
      a region with the highest HIV/AIDS rates in the United States. The theoretical
      framework incorporates Butler's (1993) and (1990) concept of performative gender
      and Collins' (2000) "controlling images" of African American women as a context
      for domestic violence in the Deep South. Two focus groups were convened to
      develop a definition of domestic violence as HIV risk; 50 in-depth individual
      interviews of HIV-positive women were subsequently conducted for specific
      information on the topic. A final focus group was conducted for verification and
      feedback. The interview data revealed that controlling images of women as
      sexualized bodies were enacted through rape, sexual coercion, and name-calling in
      intimate relationships. The main finding was that the women lacked the ability to
      control sexual activities (including condom use) in abusive relationships with
      HIV-positive men. The women used various strategies to escape abusive partners
      and to obtain treatment for HIV/AIDS. The study concludes that the links between
      gender inequity, domestic violence, and HIV transmission should appear in
      prevention materials to encourage domestic violence screening in health settings,
      and to provide abused women with information on the not-so-obvious risks of being
      infected in abusive relationships.

PMID- 15571890
TI  - The effect of maternal education on gender bias in care-seeking for common
      childhood illnesses.
AB  - This paper assessed gender bias within hospitalisation rates to ascertain whether
      differential care-seeking practices significantly contribute to excess female
      mortality. It then examined the impact of socio-economic factors, particularly
      maternal education and economic status, on gender bias. The results find both the
      clear and significant impact of gender on hospitalisation rates, as well as the
      simultaneous inability of rising education and economic status to alleviate this
      bias. A secondary analysis was conducted within a uniquely large and ongoing
      randomised control trial that sought to measure the impact of Zinc
      supplementation on hospitalisations and deaths in low-income communities in New
      Delhi, India. During the course of the study, 85,633 children were enrolled and
      monitored over one year of follow-up. Of the 430 deaths that occurred, 230 were
      female (0.57% of total females), while 200 were male (0.43% of all males).
      Despite this higher mortality amongst females (p<0.02), girls were hospitalised
      far less frequently than boys. Of the 4418 children who were hospitalised at
      least once, 2854 (64.6%) were males and only 1564 (35.4%) were females,
      indicating a significantly lower rate of care-seeking for females (p<0.00).
      Curiously, our results show that gender bias is highest amongst highly educated
      mothers, and decreases steadily for children of mothers with a middle school
      education, a primary school education, and is lowest amongst mothers with no
      formal education. Put differently, female children of mothers with no formal
      education were significantly more likely to be hospitalised than children of
      mothers with several years of formal education, even after adjusting for all
      other factors. Economic status was not found to affect the association of gender
      and hospitalisation, though overall odds of hospitalisation rose with increasing
      economic status. Paternal education was found not to be significantly related to
      hospitalisation.

PMID- 15571891
TI  - Maternal education and adolescent drug use: a longitudinal analysis of causation
      and selection over a generation.
AB  - Current evidence indicates that in the USA illegal drug use among adolescents
      between the 1980s and 1990s became significantly more prevalent in families with
      lower maternal education in comparison to families with higher maternal
      education. In this study, we examine whether this inter-generational change
      results from either (a) a changing influence of socioeconomic status on drug use,
      as predicted by the inter-generational social 'causation' hypothesis, or (b) a
      negative influence of drug use on socioeconomic status, as predicted by the inter
      generational social 'selection/drift' hypothesis. The analyses are based on the
      US National Longitudinal Study of 1979, which includes information on drug use
      for both a nationally representative sample of respondents aged 19-27 in 1984, as
      well as drug use information for the children of these respondents, who were aged
      18-27 in 1998. The results indicate that inter-generation change in cocaine and
      marijuana use resulted almost entirely from social causation. These findings
      support illegal drug use as a good candidate for analyses in the 'fundamental
      cause' tradition that seek to understand the social factors that concentrate poor
      health and health behaviors in the lower social strata over historical time.

PMID- 15571892
TI  - Low control beliefs, classical coronary risk factors, and socio-economic
      differences in heart disease in older persons.
AB  - The objective of this study was to examine whether it is through their low
      control beliefs that low socio-economic status groups have higher risks of heart
      disease, and to examine whether this mechanism is more substantial than and
      independent of the mechanism via classical coronary risk factors. In a population
      based prospective cohort study, participants were selected from 27 general
      practices in the north-eastern part of The Netherlands. In 1993, there were 3888
      men and women, 57 years and older, who were without prevalent heart disease.
      During the 5-year follow-up period, 287 cases of incident heart disease (acute
      myocardial infarction and/or congestive heart failure) were registered (7%).
      Persons with a low socio-economic status had higher risks of heart disease (RR =
      1.45 (95% CI: 1.06 - 1.99)) compared with their high status counterparts. On
      average, 4 percent of the socio-economic differences were accounted for by the
      classical coronary risk factors (e.g. smoking, hypertension) compared with 30
      percent by the control beliefs. The contribution of the latter was largely
      independent of the former. Our findings support the hypothesis that socio
      economic inequalities in heart disease-at least in middle-aged and older persons
      may be based upon differences in control beliefs, more than upon differences in
      smoking rates and other classical risk factors.

PMID- 15571893
TI  - Social isolation, support, and capital and nutritional risk in an older sample:
      ethnic and gender differences.
AB  - This study examines the relationships that exist between social isolation,
      support, and capital and nutritional risk in older black and white women and men.
      The paper reports on 1000 community-dwelling older adults aged 65 and older
      enrolled in the University of Alabama at Birmingham (UAB) Study of Aging, a
      longitudinal observational study of mobility among older black and white
      participants in the USA. Black women were at greatest nutritional risk; and black
      women and men were the groups most likely to be socially isolated and to possess
      the least amounts of social support and social capital. For all ethnic-gender
      groups, greater restriction in independent life-space (an indicator of social
      isolation) was associated with increased nutritional risk. For black women and
      white men, not having adequate transportation (also an indicator of social
      isolation) was associated with increased nutritional risk. Additionally, for
      black and white women and white men, lower income was associated with increased
      nutritional risk. For white women only, the perception of a low level of social
      support was associated with increased nutritional risk. For black men, not being
      married (an indicator of social support) and not attending religious services
      regularly, restricting activities for fear of being attacked, and perceived
      discrimination (indicators of social capital) were associated with increased
      nutritional risk. Black females had the greatest risk of poor nutritional health,
      however more indicators of social isolation, support, and capital were associated
      with nutritional risk for black men. Additionally, the indicators of social
      support and capital adversely affecting nutritional risk for black men differed
      from those associated with nutritional risk in other ethnic-gender groups. This
      research has implications for nutritional policies directed towards older adults.

PMID- 15571894
TI  - Neighbourhood inequalities in physical inactivity: the role of neighbourhood
      attractiveness, proximity to local facilities and safety in the Netherlands.
AB  - We investigated the association between the neighbourhood socioeconomic
      environment and physical inactivity, and explored the contribution of
      neighbourhood characteristics to this association. Data were analysed of 20-69
      years old participants of the Dutch GLOBE study who lived in 78 neighbourhoods of
      Eindhoven (n = 8.767). The neighbourhood socioeconomic environment was assessed
      from aggregated self-reported information of participants' education and
      occupation level, and employment status. Aspects of physical inactivity
      investigated were based on the time spent on (a) walking and cycling to shops or
      work, (b) walking, cycling and gardening in leisure time, and (c) participation
      in sports activities. Characteristics of neighbourhoods included the proximity to
      food shops, general physical design of neighbourhoods, quality of green
      facilities, noise pollution from traffic and required police attention as
      evaluated by municipal services (professionals) responsible for these
      characteristics. Compared to those living in the most advantaged neighbourhoods,
      residents living in the quartile of socio-economically most disadvantaged
      neighbourhoods were more likely to walk or cycle to shops or work, but less
      likely to walk, cycle or garden in leisure time and less likely to participate in
      sports activities (adjusted for age, sex and individual educational level).
      Neighbourhood inequalities in walking or cycling to shops or work were not
      mediated by specific neighbourhood characteristics included in our analyses. The
      increased probability of almost never walking, cycling and gardening in leisure
      time in the most disadvantaged neighbourhoods was partly mediated by a poorer
      general physical design in these neighbourhoods. Similarly, the increased
      probability of almost never participating in sports activities in the most
      disadvantaged neighbourhoods was partly mediated by larger amounts of required
      police attention. The direction of neighbourhood inequalities differs for aspects
      of physical inactivity. Neighbourhood characteristics are related to physical
      inactivity and contribute to neighbourhood socioeconomic inequalities in physical
      inactivity.

PMID- 15571895
TI  - Social inequalities in health care services utilisation after eight years of
      health care reforms: a cross-sectional study of Estonia, 1999.
AB  - Fundamental health care reforms in Estonia started in 1991 with the introduction
      of a social health insurance system. While increasing the efficiency of the
      health care system was one of the targets of the health care reforms, equity
      issues have received relatively less attention. The objective of this study is to
      provide an overview of social inequalities in health care utilisation in Estonia
      in 1999, after 8 years of large-scale reforms. Data were obtained from a
      nationally representative household interview survey including 3990 respondents
      aged 25-74 years. Health care utilisation was measured by the telephone
      consultations, visits to the general practitioner, visits to the specialist,
      visits to the dentist, and hospitalisation. These utilisation measures were
      related to variables on ethnicity, place of residence, education, income and
      employment, by means of direct standardisation and logistic regression models.
      Three different regression models were applied in order to (a) describe social
      differences in health care utilisation, (b) to assess whether these differences
      can be explained by differences in health needs, and (c) to assess the
      independent effect of each social variable net of all other social variables.
      Substantial inequalities were observed for all types of health care services and
      according to most social dimensions. Residents of rural areas were more likely to
      visit a general practitioner or to use telephone consultation, but less often
      used outpatient specialist care or dentist care. Ethnic differences were
      generally smaller, with no consistently higher use by either Russians or ethnic
      Estonians. Large differences were observed in relation to socio-economic status
      (education, income, or employment), with a more favourable socio-economic status
      being associated with higher probability to use health care services, especially
      after controlling for health needs. In case of hospitalisation, however, no
      notable social inequalities were found. These findings suggest that important
      geographic, financial and information barriers to health care utilisation exist
      after almost one decade of health care reforms in Estonia. Further health care
      reforms should aim to lessen or even remove these barriers.

PMID- 15571896
TI  - Chronic disease and mental disorder.
AB  - The aim of this study was to achieve a better understanding of the relationship
      between chronic medical illness and mental distress. Therefore, the association
      between chronic medical illness and mental distress was analysed, taking into
      account the modifying effects of generic disease characteristics (concerning
      course, control and possible stressful consequences), physical quality of life
      indicators and social and relationship problems. Panel data from the Dutch
      national Panel of Patients with a Chronic Disease (PPCZ) were used. Data from
      1788 chronically medical ill patients (nine disease categories) concerning their
      mental and physical health have been used in a cross-sectional, multivariate
      analysis. Somatic disease, generic disease characteristics and physical quality
      of life were assessed by medical doctors. Mental distress and social/
      relationship problems were assessed by questionnaire (respectively, GHQ-12 and
      Biopro). Members of the panel had more mental distress than a random community
      sample. However, there were no differences between specific somatic diseases.
      Relationship, job-related and financial problems increased the probability of
      mental disorder considerably. Relationship problems may be considered a generic
      characteristic of chronically ill patients, causing an increased risk of mental
      disorder. Poor physical health condition contributed to a higher probability of
      mental disorder as well. General practitioners, home care providers and medical
      specialists should be aware that people with chronic diseases are in general more
      at risk of mental disorder. For many chronically ill people, this risk is further
      exacerbated by social/relationship problems, and a poor level of perceived
      health.

PMID- 15571897
TI  - Oil development and health in the Amazon basin of Ecuador: the popular
      epidemiology process.
AB  - Recent decades have witnessed an increasing corporate access to and control over
      natural resources resulting in environmental degradation, inequalities and ill
      health. Since 1972, oil companies have extracted more than two billion barrels of
      crude oil from the Ecuadorian Amazon. During this process, millions of gallons of
      untreated toxic wastes, gas and oil have been released into the environment.
      Indigenous federations, peasant's movements and environmental groups have claimed
      that contamination has caused widespread damage to both people and the
      environment. This article tells the story of how the relationship between local
      organisations and research institutions developed around an epidemiological study
      constructed to address communities' concerns. Local organisations set the agenda
      of the research: they were involved in the hypothesis formulation, consulted in
      each step during the study and responsible of the dissemination of the findings.
      This process is known as popular epidemiology. Practical and personal issues and
      dilemmas faced during the research process are discussed with emphasis on the
      communication and dissemination of the findings. The article concludes the need
      of alliances between communities and researchers in order to protect health and
      environment. Popular epidemiology is an essential approach for public health
      researchers to reaffirm their roots in improving public health as a primary
      value.

PMID- 15571898
TI  - Reform strategies in Georgia and their impact on health care provision in rural
      areas: evidence from a household survey.
AB  - The transition resulting from the break-up of the Soviet Union significantly
      affected the health care systems and population health status in the newly
      independent States. The available body of evidence suggests that contraction of
      public resources resulting from economic slowdown has led to the proliferation of
      out-of-pocket payments and private spending becoming a major source of finance to
      health service provision to the population. Emerging financial access barriers
      impede adequate utilization of health care services. Most transition countries
      embarked on reforming health systems and health care financing in order to tackle
      this problem. However, little evidence is available about the impact of these
      reforms on improved access and health outcomes. This paper aims to contribute to
      the assessment of the impact of health sector reforms in Georgia. It mainly
      focuses on changes in the patterns of health services utilization in rural areas
      of the country as a function of implemented changes in health care financing on a
      primary health care (PHC) level. Our findings are based on a household survey
      which was carried out during summer 2002. Conclusions derived from the findings
      could be of interest to policy makers in transitional countries. The paper argues
      that health financing reforms on the PHC level initiated by the Government of
      Georgia, aimed at decreasing financial access barriers for the population in the
      countryside, have rendered initial positive results and improved access to
      essential PHC services. However, to sustain and enhance this attainments the
      government should ensure equity, improve the targeting mechanisms for the poor
      and mobilize additional public and private funds for financing primary care in
      the country.

PMID- 15571899
TI  - Providing solutions--defining problems: the imperative of disease prevention in
      genetic counselling.
AB  - Common sense states that problems make people look for solutions. This article
      proposes the contrary, i.e. that solutions provide the framework within which
      certain problems can be stated and handled. Drawing on observations of cancer
      genetic counselling in Denmark and official recommendations concerning the
      practice of genetic counselling, this article explores how the new prophylactic
      possibilities become the lens through which risk factors are identified and
      defined as problems that require action. In particular, the question of how new
      possibilities to prevent hereditary disease challenge the traditional non
      directive ethos of clinical genetics provides the occasion to analyse
      governmentality processes in clinical genetic dialogues. The article argues that
      an imperative of choosing disease prevention in genetic counselling transforms
      the notion of non-directiveness as well as the notions of autonomy and informed
      consent. The transforming event is the transmission of expert knowledge on
      genetic risk from counsellor to counsellee. This process of knowledge
      transmission creates autonomous individuals who, through the medium of choice,
      consent voluntarily to take personal responsibility for themselves and their
      relatives. Conceived as a health technology, genetic counselling is a practice
      through which hegemonic knowledge claims about saving lives by acting responsibly
      is created. Disease prevention as the solution to increased risks comes to stand
      out as the right way of relating to oneself, the family, and society.

PMID- 15571900
TI  - The use of patient reported outcome measures in routine clinical practice: lack
      of impact or lack of theory?
AB  - This paper applies a theory-driven approach to explore why the use of patient
      reported outcome (PRO) measures in clinical practice, in particular, health
      related quality of life (HRQoL) instruments, has little or no apparent influence
      on clinical decision making. A theory-driven approach involves combining
      knowledge of whether and how an intervention works. It is argued that such an
      approach is currently lacking within the literature evaluating the effectiveness
      of feeding back HRQoL information to clinicians. The paper identifies a number of
      mechanisms that might give rise to the expected outcomes that are currently
      implicit within the design of the intervention and hypotheses specified within
      the trials evaluating the use of HRQoL measures in clinical practice. It then
      examines how far current clinical practice matches these mechanisms and in doing
      so, a number of possible explanations for the lack of impact of HRQoL on clinical
      decision making are reviewed. The influence of HRQoL information on clinical
      decision making depends on a large number of factors related to the design of the
      intervention, patients' and clinicians' desire to discuss HRQoL issues within the
      consultation and the legitimacy that clinicians give to HRQoL instruments. To
      date, knowledge of how the feedback of HRQoL information to clinicians might
      improve doctor-patient communication or clinical decision making has yet to
      sufficiently inform an assessment of whether these aspects of patient care are
      improved. The paper concludes by specifying how the feedback of HRQoL information
      to clinicians might be modified to maximise its impact on clinical decision
      making.

PMID- 15571901
TI  - The teleo-affective limits of end-of-life care in the intensive care unit.
AB  - This paper explores the relevance of a specific kind of sensed connectedness or
      'teleo-affectivity' to the organisation and enactment of end-of-life care.
      Referred to as heedful inter-relating, this teleo-affective connectedness has
      been found to occur among employees as they carry out their highly complex and
      dangerous work. This paper focuses on the proposals put in the literature for
      confronting the complexity of end-of-life care in the intensive care unit (ICU),
      and inquires into the positionings incurred in and around end-of-life care in one
      specific unit, with the aim of gauging the pertinence of heedful inter-relating
      to end-of-life care in ICU. The paper argues that while several commentators
      appear to be calling for enhanced heedful conduct in end-of-life care, ICU
      practices may not admit the kind of heedful inter-relating that is evident in
      high-reliability organisations such as nuclear aircraft carriers. We suggest it
      may be unwise to gauge intensive care units' complexity purely against the brief
      of realising cultural scripts of the dying, and that ICU in fact manifests a
      broader societal concern necessitating a more variegated composition: to devise
      multiple ways to contain the impression and impact of (the meaning) death for
      society (societies) generally.

PMID- 15571902
TI  - Habitual self-control and the management of health behavior among heart patients.
AB  - This study examined the predictive power of habitual self-control on health
      behaviors among 381 heart surgery patients in Germany. Habitual self-control and
      other trait predictors (dispositional optimism, generalized self-efficacy
      beliefs, health locus of control beliefs) were assessed before and six months
      after surgery. Social-cognitive predictors of health behavior (behavior-specific
      self-efficacy and outcome beliefs, intentions) were assessed only before surgery.
      Outcomes were dieting, physical exercise, and smoker status before and after
      surgery. Compared to other trait variables, habitual self-control emerged as a
      superior predictor of the behavioral outcomes. Further, habitual self-control
      explained unique variance in dieting and physical exercise beyond proximal
      behavior-specific predictors (i.e., self-efficacy beliefs, intentions) that are
      supposed to display direct effects on behavior. Results of hierarchical linear
      regressions provided partial support for the assumption that habitual self
      control strengthens the intention-behavior congruence. In prospective analyses
      predicting dieting at the 6-month follow-up an interaction between habitual self
      control and dieting intentions emerged indicating that self-control supported
      dieting among patients with imperfect (moderate) dieting intentions only. In sum,
      the results suggest that habitual self-control may be a useful construct in
      research on health behavior management, in particular when long-term maintenance
      of health behavior is the target.

PMID- 15571903
TI  - Towards a geography of fitness: an ethnographic case study of the gym in British
      bodybuilding culture.
AB  - During recent years, research in health geography has engaged with peoples'
      health as well as diseases, an interest reflected by therapeutic geographies and
      geographies of public health. At the same time, studies have focused on micro
      contexts such as the body, reflected in geographies of diseased and disadvantaged
      bodies. However, little research has combined elements of the two approaches and
      engaged in research on active healthy bodies and fitness. Equally the sub
      discipline of sports geography provides little insight into fitness activities
      because this research has tended to focus on elite sports, their fans and
      facilities. Given these contexts, a detailed case study is presented to
      demonstrate the potential for geographical research on fitness. Through an
      observational study of a specialist gym facility, the study investigates how
      bodybuilding culture and place are co-produced. Indeed, the gym provides a
      narrative resource and a crucial setting for individual body projects and
      collective body culture which involve social conflicts, cohesions and
      hierarchies, illegal and potentially health harming activities, as well as
      personal comfort and therapeutic attachments. It is argued that beyond this case
      study, many activities crosscut health maintenance, or conversely risks to
      health, and the enjoyment of sports and fitness. A greater emphasis therefore at
      the sub-disciplinary interface of sports and health geography on hybrid 'fitness
      geographies' may help researchers towards a more comprehensive understanding, and
      coverage, of health issues in society.

PMID- 15571904
TI  - Disclosing and responding to cancer "fears" during oncology interviews.
AB  - Video-excerpts from routine oncology interviews are examined to reveal how
      patients demonstrate and doctors respond to "fears" about cancer. Vocally and
      visually, embodied impacts of dealing with dreaded consequences of cancer are
      apparent when addressing both good and potentially bad cancer news. Even a
      "brush" with cancer can promote negative and ongoing impacts provoking unresolved
      illness dilemmas. We reveal how, in the midst of extending answers and initiating
      concerns, patients exhibit trepidations when volunteering narrative information
      about their medical history and experience of symptoms. In response, doctors are
      shown to acknowledge yet exhibit minimal receptiveness to patients' lifeworld
      disclosures and demonstrations (e.g., redirecting attention away from patients'
      concerns by offering "textbook" symptoms and related pursuits of biomedical
      agendas). Discussion focuses on interactional criteria for identifying "fears",
      patients' lay orientations to medical visits, and implications for refining
      educational workshops for oncologists.

PMID- 15571905
TI  - Relationship between respiratory syncytial virus infection and acute otitis media
      in children.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is among the major causes of
      respiratory tract infection in infants and young children, and concomitant acute
      otitis media (AOM) often develops. However, there are only a few reports about
      AOM associated with RSV infection. METHODS: Two hundred and thirty children who
      were diagnosed as having RSV infection were studied by enzyme immunoassay
      (Testpack RSV) at the Department of Pediatrics of Tohoku Rosai Hospital from 1
      November 2001 to 31 October 2002. In the patients with AOM, bacterial culture and
      detection of RSV antigen in the middle ear fluid (MEF) by enzyme immunoassay were
      performed, and the outcome was investigated. RESULTS: Among the 230 children, 120
      (52.2%) were found to have AOM. In children under 2 years of age, the incidence
      of AOM was significantly higher (73.1%) than in the older children (29.7%). RSV
      antigen was positive in the MEF of 36 out of 52 patients with AOM (69.2%). In 24
      of the 46 patients in whom both RSV antigen detection and bacterial culture of
      MEF were performed, RSV antigen was detected and bacterial culture was negative.
      Although the outcome of the first episode of AOM following RSV infection was
      favorable, relapse was observed in 31% of the patients. CONCLUSION: These results
      confirm that patients with RSV infection have a high risk of AOM, especially
      children younger than 2 years of age, and suggest that RSV may be a direct cause
      of AOM at least in the early stage of infection with this virus. The necessity of
      performing careful follow-up of AOM after resolution of symptoms is suggested
      because relapse is common.

PMID- 15571906
TI  - Subjective evaluation of post-tympanoplasty hearing in relation to the pure tone
      threshold.
AB  - OBJECTIVE: In the year 2000, the Otological Society of Japan proposed a new
      criteria to assess the levels of hearing known as Criteria 2000. However, these
      criteria are intended to assess pure tone threshold after tympanoplasty and the
      results do not necessarily reflect the hearing condition from the patient's
      perspective. Thus, it is essential to study the relationship between the
      subjective evaluation of post-operative hearing based on the patient's own
      assessment and the objective assessment by audiometry. METHODS: The present study
      is a questionnaire-based survey on the levels of post-operative hearing in 460
      patients whose degree of satisfaction with their levels of hearing was assessed
      by visual analogue scale (VAS). The hearing level was assessed based on the
      Criteria 2000 established by the Otological Society of Japan. RESULTS: The post
      operative results indicated a success rate of 78.7%. According to the
      questionnaire-based survey, 64.4% patients considered their hearing as
      "improved". The average VAS score was the highest in the "improved" group and
      gradually decreased when in the "deteriorated" group. The highest success rate
      was obtained in patients who assessed their hearing as "improved" and the lowest
      rate was seen in those who assessed their hearing as "deteriorated". On the other
      hand, the success rate in the three groups, "slightly improved", "unchanged", and
      "slightly deteriorated", was almost similar and did not relate to the objective
      audiometry findings. Therefore, except for the "improved" and deteriorated"
      groups, there is no relation between the subjective self-assessment and the
      objective post-operative hearing. CONCLUSION: A bi-directional approach, one from
      an audiological (objective) and one from the patient's perspective (subjective),
      especially using VAS, is quite useful for the post-operative assessment of
      hearing.

PMID- 15571907
TI  - Gas diffusion across the tympanic membrane in chinchillas: effect of repeated
      perforations.
AB  - OBJECTIVE: Earlier studies documented a slow diffusion of gas across the tympanic
      membrane (TM) in humans and animals. However, structural changes caused by
      repeated TM perforations could affect gas diffusion rates. This possibility was
      evaluated using a chinchilla model. METHODS: In six chinchillas, the right TM was
      perforated four times at 2-week intervals; the left TM served as a control.
      Approximately 12 weeks after the fourth perforation and when the right TMs had
      healed, a probe was introduced into the external canal and sealed to the
      environment. For 120 min, pressure in the probe was continuously monitored and
      probe gas was sampled at 10 min intervals and analyzed for composition by online
      mass spectrometry. Percent compositions for CO(2) and O(2) were calculated and
      these data were recast as partial-pressure versus time functions. The information
      contained in those functions was used to estimate time-constants for transTM O(2)
      and CO(2) diffusion. RESULTS: In all experiments, CO(2) percent composition in
      the probe increased as a curvilinear function of time while that for O(2)
      decreased linearly. For all animals and both gases, the rate of change in probe
      partial-pressure was greater for the right TM. Average values of the right and
      left time-constants were (6.7 +/- 2.4) x 10(-3) and (4.2 +/- 2.2) x 10(-3)min(
      1)TM(-1) for CO(2), and (2.3 +/- 0.8) x 10(-3) and (1.5 +/- 0.5) x 10(-3)min(
      1)TM(-1) for O(2). Between side differences in these time-constants were
      statistically significant (P < 0.05, 2-tailed, paired, Student's t-test). The
      average right/left, transTM time-constant ratio was 1.66 +/- 0.43 for CO(2) and
      1.61 +/- 43 for O(2); both were significantly different from a value of 1.0 (P <
      0.05, 2-tailed Student's t-test). CONCLUSION: These results document an increased
      rate of diffusive gas exchange across TMs that had been repeatedly perforated.
      This effect may be caused by structural thinning secondary to scar formation and
      could have implications for middle ear pressure regulation in ears with a history
      of repeated myringotomies and/or tympanostomy tube insertions.

PMID- 15571908
TI  - The effects of hypoxia, premature birth, infection, ototoxic drugs, circulatory
      system and congenital disease on neonatal hearing loss.
AB  - OBJECTIVES: To investigate the incidence of neonatal hearing loss in well-baby
      populations and in a neonatal intensive care unit and to identify potential risk
      factors for hearing loss in a neonatal intensive care unit which the Joint
      Committee on Infant Hearing (JCIH) had not recommended. METHODS: Auditory
      screening was conducted in 226 infants (452 ears) born in Tohoku University from
      2000 to 2001. The cases included 124 healthy newborn infants (248 ears), and 102
      newborn infants (204 ears) treated in the neonatal intensive care unit (NICU).
      Hearing impairment was confirmed through a primary screening of the automated
      auditory brainstem response (AABR) and a secondary test of the auditory brainstem
      response (ABR) with otolaryngologic evaluation. Based on these examinations, we
      divided infants into two groups, 'Pass' and 'Refer'. RESULTS: Nine patients (15
      ears) in Refer group were identified through our protocol. The incidence of the
      Refer group was 0.8% (1 out of 124) in the well-baby nursery, 7.8% (8 out of 102)
      in the NICU populations. The infants in Refer group were shown to have a higher
      incidence of congenital infection (P < 0.01), high C-reactive protein (CRP) (> or
      =10 mg/dl), chromosomal aberration, and central nervous system abnormality (P <
      0.05). On the other hand, there were no statistical differences between the Pass
      and Refer groups in NICU, birth weight (<2200 g), gestational age, the values of
      total serum bilirubin, the values of arterial blood gases (pH, PaCO2 , PaO2 ),
      percutaneous oxygen saturation (SpO2), hemodynamics (blood pressure and heart
      rate) (P > 0.1). Respiratory status such as the Apgar score (the abbreviation for
      appearance, pulse, grimace, activity, respiration) (1 min; < or =4), (5 min; < or
      =6), Silverman retraction score, ototoxic drug use, respiratory distress syndrome
      (RDS), Meconium aspiration syndrome (MAS), and persistent pulmonary hypertension
      of newborn (PPHN) were also not statistically related to hearing loss (>0.999).
      CONCLUSION: Even in a small number of infants, there are positive relationships
      between hearing loss and congenital infection, high CRP (> or =10 mg/dl),
      chromosomal aberration and central nervous system abnormality. The CRP (> or =10
      mg/dl) variable are not listed in the high-risk register published by the JCIH,
      but we can say that the variable may predict hearing impairment in our patient
      population. The possibility of autosomal recessive inheritance of genes for
      deafness is supposed when newborns have no other risk factors for hearing loss.
      This leads us to conclude that hearing screening is an effective way to find out
      hearing loss population.

PMID- 15571909
TI  - An analysis of correlation between the unusual location of the jugular bulb and
      audiovestibular symptoms.
AB  - OBJECTIVE: Case reports indicate that abnormal location of the jugular bulb (JB)
      may result with some vestibular and audiological symptoms. The aim of this study
      is to analyze the correlation between the radiological view of the JB and
      audiovestibular findings and to clarify its possible role for Meniere-like
      problems. METHOD: Fifty-six patients, who had abnormal view of the JB on
      computerized tomography (CT) were selected to the study in this prospective case
      review. They were classified in three groups (Group-I; Lateral, Group-II;
      Intermediate and Group-III; Medial), according to the location of the JB.
      Patients were subjected to audiogram and vestibular tests (Dix-Hallpike maneuver,
      fistula test, vestibulospinal tests, electronystagmography (ENG)). RESULTS: JB
      was compressing on the cochlear aqueduct (CA) in two patients in group-II.
      Seventeen out of 25 patients in group-III had radiological evidence of
      obstruction of vestibular aqueduct (VA). 19 patients had neurosensorial and four
      patients had conductive hearing loss. All of the patients in group-I and nine of
      the patients in group-II gave normal caloric response to stimulation. Twelve of
      19 patients in group-III demonstrated canal paresis ranging from 22 to 80%.
      CONCLUSION: Present study points out that there is a high correlation between HJB
      and vestibular problems in symptomatic cases. In patients who have HJB without
      classic vertigo attacks subclinical involvement of the vestibular system has been
      observed on ENG recordings. These findings imply that radiological existence of
      HJB may be a predisposing factor for Meniere-like complaints.

PMID- 15571910
TI  - A head-mounted visual stimulator for neurotological examination.
AB  - OBJECTIVES: Presently, the neurotological tests, using visual stimulation, such
      as optokinetic nystagmus test (OKN), eye-tracking test (ETT) is being widely used
      for the diagnosis of vertigo or disequilibrium. The problems of these tests are
      the large size of the visual stimulator and therefore a wide space requirement.
      Even if a small apparatus is developed, the apparatus itself would be very
      expensive. In this study, we developed a small visual stimulation test system
      comprising the virtual visor, which receives an image for visual stimulation from
      an on-line computer. METHODS: Using smooth pursuit and optokinetic stimulation
      onto a virtual visor we assessed the ENG recording in 20 normal subjects. RESULT:
      We found the 30 degrees /s OKN, horizontal eye tracking were adequately
      stimulated by this technique with reliable results. CONCLUSION: This new method
      of smooth pursuit and optokinetic stimulating by a virtual visor is capable of
      producing reliable results and may be used in the clinical laboratory of vertigo.
      However, this stimulator also has some limitations, mainly because of the visual
      angle of the virtual visor stimulator.

PMID- 15571911
TI  - Effects of aminoglycoside administration on cochlear elements in human temporal
      bones.
AB  - OBJECTIVE: Although there have been numerous reports on the relationship between
      the period of aminoglycoside administration and cochlear damage in animals, to
      date there have been no such studies in humans. The purpose of this study is to
      observe the early and late cochlear effects of aminoglycoside administration on
      hair cells, spiral ganglion cells, stria vascularis, and spiral ligament.
      METHODS: Specimens were divided into three groups. Group I included "normal"
      temporal bones with no histopathologic findings of otitis media and no history of
      otologic or ototoxic drug administration. Group II consisted of temporal bones
      that received aminoglycosides within 2 weeks before death and group III of
      temporal bones that had aminoglycosides from 2 weeks to 6 months prior to death.
      Patients in groups II and III received gentamycin, kanamycin or tobramycin.
      Temporal bones were excluded from groups II and III if patients had a history of
      otologic disease or other ototoxic drugs. All temporal bones were examined under
      light microscopy. Standard cytocochleograms and spiral ganglion cell
      reconstructions were done on all temporal bones. Morphometric measurements of
      areas of stria vascularis were made in all turns of the cochlea on mid-modiolar
      sections. Spiral ligament was divided into four segments according to the
      locations of different types of fibrocytes. The mean loss of fibrocytes in each
      segment was estimated. RESULTS: The percentages of intact outer hair cells in the
      basal turn were significantly greater in group I compared to groups II and III.
      The mean area of the stria vascularis in the apical turn was significantly less
      in groups II and III compared to group I. CONCLUSION: This study demonstrates
      that in a short period (within 2 weeks) after aminoglycoside administration, a
      decrease in hair cells and in the area of the stria vascularis occurred.

PMID- 15571912
TI  - Outer hair cell activity of the cochlea in patients with iron deficiency anemia.
AB  - OBJECTIVE: Iron deficiency anemia is a common disorder, which has been reported
      to affect the auditory system. However, there are some conflicting points related
      with the pattern of hearing impairment. The aim of this study is to analyze the
      outer hair cell activity of the cochlea in patients with iron deficiency anemia.
      METHOD: Pure-tone audiometry (PTA) (250-6000 Hz) and distortion product
      otoacoustic emission (DPOAE) results of 42 patients with iron deficiency anemia
      and 22 healthy, age and sex matched subjects for the control group were compared.
      Cubic DPOAEs (2f1-f2) were obtained at 65 and 55 dB sound pressure level (SPL).
      DP grams were plotted as a function of f2 and signal-to-noise ratio (SNR) was
      specified as the difference in decibels SPL between DPOAE amplitude and the
      ambient noise level at a given f2. In DP grams, DP amplitudes and noise levels
      obtained from the baseline measurements were presented as the upper and lower
      limits of DP amplitude and noise level that were the 10th and 90th percentiles
      calculated by adding and subtracting standard deviations and from mean baseline
      DP amplitude and noise level. Independent-samples t-test is used for comparison
      of the groups. RESULTS: Pure-tone audiometry was normal in patients with iron
      deficiency anemia and control subjects and there was no significant difference in
      comparison of DPOAE in both groups and both sides and the results were between
      two percentiles (P > 0.05). CONCLUSION: The results of the present study did not
      support a casual relationship between the iron deficiency anemia and the auditory
      dysfunction on the basis of DPOAE.

PMID- 15571913
TI  - Effects of glucocorticoid receptor antagonist on CAPs threshold shift due to
      short-term sound exposure in guinea pigs.
AB  - OBJECTIVE: The steroid drugs are used for the standard treatment of sudden
      sensorineural hearing loss. However, clinical results on the effect of
      glucocorticoids in acoustic trauma have not yet been understood well. The effects
      of glucocorticoid receptor (GR) antagonist, mifepristone, on the cochlea
      sensitivity loss due to short-term sound exposure were studied in the guinea pig.
      METHODS: Mifepristone (20 mg/kg) was injected subcutaneously immediately after
      the noise exposure to 4 kHz pure tone of 100 or 120 dB SPL for 10 min and also at
      1 day and 3 days later. Seven days after the sound exposure, the compound action
      potentials (CAPs) of the cochlear nerve and the 2f(1)-f(2) distortion product oto
      acoustic emissions (DPOAEs) were recorded. RESULTS: No significant CAP threshold
      losses were observed in either mifepristone or saline administration after the
      exposure at 100 dB SPL. After the exposure at 120 dB SPL, administration of
      mifepristone elevated the CAP threshold at 5-8 kHz significantly as compared with
      the saline administration. The DPOAE output shifts of both saline and
      mifepristone groups were similar to each other. CONCLUSION: Mifepristone may
      influence inner hair cells (IHCs) and afferent nerve fibers beneath the IHC
      without having influence on outer hair cells (OHCs). It is suggested that
      glucocorticoid plays an important role in the improvement of hearing impairment
      after loud sound exposure.

PMID- 15571914
TI  - Irradiation impairment of umami taste in patients with head and neck cancer.
AB  - BACKGROUND: Previous studies have reported the alteration of the four basic
      tastes (sweet, salty, sour and bitter) in patients with head and neck cancer
      (HNC) during radiotherapy. However, there has been no investigation on the
      function of umami taste, a novel basic taste recognized recently, during head and
      neck irradiation. OBJECTIVE: To investigate the recognition threshold of umami
      and the four basic tastes at different irradiation dose intervals during
      radiotherapy for head and neck cancer. METHODS: In 30 patients with malignant
      neoplasm of head and neck, objective taste thresholds were examined by use of a
      whole-mouth method at pre-radiotherapy, irradiation doses at 15, 30, 45, and 60
      Gy, respectively. Subjective taste loss and some distresses were recorded
      simultaneously. RESULTS: Sweet, sour, salty, and bitter tastes showed temporarily
      and slightly increased thresholds during the treatment, but no statistical
      difference was found between the threshold at pre-radiotherapy and that at 15,
      30, 45, and 60 Gy in any taste quality (all P > 0.05). Significantly impaired
      threshold of umami taste was revealed at 30 Gy (P < 0.05) and remained throughout
      the following treatment (at 45 and 60 Gy, both P < 0.01). Subjective taste
      impairment, appetite loss and satisfaction with the current state tended to
      deteriorate significantly during the irradiation. Mean body weight of the
      patients experienced a continuous loss, decreasing from an average of 60.4 kg
      before treatment to 57.3 kg at 60 Gy (P < 0.01). Scores of satisfaction with
      current state showed a significant correlation with umami taste thresholds (P =
      0.035). CONCLUSION: The clinical impairment pattern of umami taste is different
      from that of the other four basic tastes in HNC patients during radiotherapy.
      Impaired umami taste acuity plays an important role in impacting the quality of
      life of the patients irradiated to the head and neck.

PMID- 15571915
TI  - Reovirus oncolysis in human head and neck squamous carcinoma cells.
AB  - OBJECTIVE: To determine whether reovirus, a double-standed RNA virus is effective
      on the growth of a human head and neck squamous cell carcinoma cell line.
      DESIGNS: In vitro cell proliferation assay, KB cells, a human oral floor squamous
      cell carcinoma cell line, were treated with reovirus and the number of cells was
      quantitated by an assay, using trypan blue staining. In vivo tumor growth assay,
      KB cells were injected subcutaneously into athymic nude mice, which were given an
      intratumoral injection of reovirus to a maximum four times in every week. The
      tumor size was measured once a week. Simultaneously, apoptosis and necrosis of KB
      cells were investigated, using technique of immunohistochemistry. RESULTS: In
      vitro, the multiplication of the KB cell was inhibited depending on the
      concentration of reovirus. In vivo, athymic nude mice bearing KB tumors were
      injected with the virus intratumorally, and the tumor growth was suppressed
      proportionally depending on the injection time of reovirus. Necrosis was
      recognized extensively in the pathological specimen. On the other hand, apoptosis
      inducing effect was not obvious in these specimen. CONCLUSIONS: Reovirus
      suppressed tumor growth of KB cells in vivo as well as in vitro. The possibility
      that reovirus could become the means of treatment for head and neck carcinoma,
      was suggested with further work.

PMID- 15571916
TI  - The management of possible fishbone ingestion.
AB  - OBJECTIVE: We assessed the usefulness of computed tomography (CT) in cases of
      suspected impaction of fish bones in the esophagus. The findings of this study
      were also compared with those of studies in which surgery was used to remove or
      confirm the presence of fish bones. We accordingly propose a management protocol
      to ensure optimum outcome for patients with a history of fish bone ingestion.
      METHODS: X-ray and CT imaging were performed in 76 patients in whom esophageal
      impaction of fish bones was suspected. RESULTS: Plain X-ray revealed impacted
      fish bones in 17 patients (22%), soft-tissue swelling but no evidence of foreign
      body in 5 (7%), and no abnormal findings in 54 (71%). These findings were
      apparent on CT scans in 31 (41%), 8 (10%), and 37 (49%), respectively. Of the 31
      patients in whom CT revealed a fishbone, 17 (55%) also exhibited X-ray evidence
      of foreign body. Of the remainder, X-ray revealed only soft-tissue swelling in 3
      (10%), and was unremarkable in 11 (35%). Among the 5 patients in whom X-ray
      demonstrated only soft-tissue swelling, CT was positive for foreign body in 3
      (60%). Of the 54 patients in whom X-ray appearances were normal, CT revealed
      foreign bodies in 11 (20%) and other abnormalities in 6 (11%). CONCLUSION: In the
      present study, sensitivity and specificity of plain X-ray was 54.8% (17 of 31)
      and 100% (45 of 45), respectively. However, for CT, both sensitivity and
      specificity were 100%. CT was determined to be very useful in the diagnosis of
      impacted fish bones in the esophagus.

PMID- 15571917
TI  - Prognostic significance of EGF receptor expression in early glottic cancer.
AB  - OBJECTIVE: A positive relationship between epidermal growth factor receptor
      (EGFR) expression and radioresistance has been shown both in vitro and in vivo.
      In a group of 31 patients with early glottic cancer treated with definitive
      radiotherapy, the relationship of EGFR expression with patient and tumor related
      parameters were analyzed and the prognostic effect of EGFR expression on local
      control (LC) was assessed. MATERIAL AND METHOD: Between 1991 and 2001, 114
      patients with early glottic (Tis-T2N0M0) squamous cell carcinoma were treated
      with radiotherapy at our institution. Among these, 31 patients whose pretreatment
      pathology specimens were available for immunohistochemical analysis formed the
      study population. Median age was 64 (46-77). Anterior commissure involvement was
      evident in 12 (38.7%) patients. Distribution according to T stage was as follows:
      Tis 6 (19.3%), T1 22 (71%), and T2 3 (9.7%). Histopathological grades of the 25
      T1-2 tumors were 10/25 (40%) grade 1, 9/25 (36%) grade 2 and 6/25 (24%) grade 3.
      Our radiotherapy regimen was 66-70 Gy in 33-35 fractions over 6.5-7 weeks. The
      median follow-up period was 45 months (range, 5-116). Following
      immunohistochemical staining, quantitative immunohistochemistry (IHC) was
      performed by image analysis software and stained tumoral area percentage (STAP)
      was identified. The cut-off value was < or =5% versus >5%. The relationship of
      EGFR expression with patient (age) and tumor related (T stage, histopathological
      grade, and anterior commissure involvement) parameters was evaluated using chi
      square test. Prognostic significance of EGFR expression, age, T stage,
      histopathological grade, and anterior commissure involvement on LC was assessed
      using log-rank test. RESULTS: No difference was found in EGFR content
      distribution in relation to age, T stage, histopathological grade, and anterior
      commissure involvement. In the univariate analysis including age (< or =60 versus
      >60), T stage (Tis and T1 versus T2), histopathological grade (grade 1 and 2
      versus grade 3), anterior commissure involvement (present versus absent), and
      EGFR expression (high versus low), only T stage and EGFR expression were found to
      be significant prognostic factors affecting LC (P = 0.0006 and P = 0.03,
      respectively). CONCLUSION: The results of this series support that EGFR
      expression is an unfavorable prognostic factor in early glottic carcinomas. For
      this reason EGFR IHC may be considered for selecting patients for more aggressive
      therapies (radiotherapy with different fractionation schemes or surgery) or
      enrollment into trials targeting EGFR signaling pathways.

PMID- 15571918
TI  - Zinc deficiency in patients with idiopathic taste impairment with regard to
      angiotensin converting enzyme activity.
AB  - OBJECTIVE: The present study aimed at measuring the ratio of apo/holo activities
      of angiotensin converting enzyme (ACE) ratio in the serum of patients with taste
      impairment to evaluate their status of zinc nutrition. METHODS: Nineteen patients
      complaining of taste impairment were divided into two groups: zinc-deficiency
      taste impairment (n=6) and idiopathic taste impairment (n=13) and compared to 30
      volunteers. Zinc concentrations in the serum were measured by atomic absorption
      spectrometry (normal values: 64-111 microg/dl). Patients with zincemia values of
      <63 microg/dl with no history of other disorder or medication known to cause
      dysgeusia were diagnosed as zinc deficient, while those with the same condition
      and values >64 microg/dl were considered to belong to the idiopathic group. The
      activities of ACE in the serum were measured spectrophotometrically as the
      activity of the holo-ACE, and after addition of 80 microM of zinc to the serum in
      vitro, the increase of ACE activity over initial value in the serum was
      determined as that of the apo-ACE. Finally, the apo/holo-ACE activities ratio was
      used as an index of zinc nutritional status. RESULTS: The mean concentrations of
      zinc in the serum were 77.4+/-8.4 microg/dl in volunteers, 77.6+/-8.4 microg/dl
      in the idiopathic patients and significantly decreased at 55.7+/-5.8 microg/dl in
      zinc-deficiency patients. ACE activities in the serum were 14.7+/-7.6, 14.5+/-4.0
      and 14.1+/-3.3 IU/l in volunteers, the idiopathic group and zinc-deficiency taste
      impairment group, respectively. The mean ACE ratios were 1.10+/-0.6% in
      volunteers and significantly increased at 9.8 +/- 4.0% in the idiopathic group
      and at 13.7+/-6.6% in zinc-deficiency taste impairment group. CONCLUSION: The
      results of the present study indicated that zinc deficiency is a predominant
      factor underlying hypogeusia even when zinc concentrations are within normal
      ranges in the serum and show that clinically, ACE ratio may be a more sensitive
      indicator of the zinc nutritional status than measuring zinc concentration in the
      serum.

PMID- 15571919
TI  - A rare spontaneous temporal meningoencephalocele with dehiscence into the
      pterygoid fossa.
AB  - We present an extremely rare case of basal meningoencephalocele that protruded
      into the left pterygoid fossa from the middle cranial fossa. After a 30-year-old
      woman experienced a generalized tonic-clonic seizure, computed tomography (CT)
      scanning showed a large bone defect of the left middle cranial base. A mass
      lesion with low signal intensity on T1- and high signal intensity on T2-weighted
      magnetic resonance imaging (MRI) was visualized in the left pterygoid fossa. A
      biopsy was performed through the transantral approach. Because cerebrospinal
      fluid (CSF) was observed to flow from the mass lesion, it was diagnosed as a
      meningoencephalocele. CT showed bone defects in the skull base and a well
      circumscribed expansile mass lesion. MRI demonstrated that the brain parenchyma
      extended into a CSF-filled meningocele. These findings demonstrate that CT and
      MRI provide adequate information for the diagnosis of meningoencephaloceles.

PMID- 15571920
TI  - Brain abscess secondary to the middle ear cholesteatoma: a report of two cases.
AB  - We experienced two cases of brain abscess secondary to middle ear cholesteatoma.
      One, a 61-year-old woman, presented with left otalgia, appetite loss and nausea.
      The computed tomography obtained on admission revealed a middle ear
      cholesteatoma. The magnetic resonance image showed the presence of a brain
      abscess in the cerebellum. The brain abscess was drained and the cholesteatoma
      was removed using the canal down procedure under general anesthesia. Part of the
      cholesteatoma invaded the posterior cranial fossa was could not be removed from
      the otological surgical field. The patient has been under observation as an
      outpatient for 6 months already and no abnormal signs have been detected. The
      other patient, a 55-year-old man, was admitted to our hospital for a detailed
      examination because he had right otalgia and progressive headache. The
      examination of spinal fluid obtained by lumbar puncture showed marked elevation
      of the white blood cells count. Computed tomography revealed a middle ear
      cholesteatoma. The magnetic resonance image obtained on admission showed an area
      of low-intensity encapsulated by an area of high-intensity in the right temporal
      lobe. The abscess was drained and the cholesteatoma was removed using the canal
      down procedure under general anesthesia. The patient has been under observation
      for 1 year already and has presented no signs of recurrence.

PMID- 15571921
TI  - A case of pleomorphic adenoma of the nasal septum.
AB  - We report a rare case of pleomorphic adenoma arising from the nasal septum. A 32
      year-old woman presented with a 3-week-history of left-sided nasal obstruction.
      Computed tomographic scans revealed an oval mass, measuring about 30 mm in its
      greatest dimension, in the left anterior nasal cavity. The tumor arose from the
      anterior part of the nasal septum, and was removed endoscopically with endonasal
      approach. The microscopic finding showed a lobular and duct-like structures
      consisting of a loose chondromyxoid stroma. This lesion had histological
      characteristics of a pleomorphic adenoma, and this was confirmed by
      immunohistochemical expression of cytokeratin and S-100 protein. Her post
      operative course was uneventful, and she is currently free from the disease 8
      months after surgery. Diagnosis, clinical behavior and treatment of pleomorphic
      adenoma of the nasal septum are reviewed from perusal of the literature.

PMID- 15571922
TI  - Neck metastasis of a myxoid liposarcoma of the lower extremity.
AB  - We report the clinical features of two cases presenting metastatic neck tumors
      (in the anterior neck and submandibular regions) secondary to myxoid liposarcoma
      of the lower extremity. Both cases underwent repeated resection of primary
      legions of the lower extremities because of recurrences. Such repeated surgical
      procedures are thought to be a risk factor for distant metastasis resulting from
      hematogeneous dissemination of tumor cells, although there is considerable debate
      about multicentricity versus metastasis in liposarcomas. Where possible, therapy
      for liposarcomas should initially comprise complete and wide resection of the
      lesions. Combined therapy consisting of surgery and postoperative radiation and
      chemotherapy should be investigated in the future.

PMID- 15571923
TI  - Synthetic glycolipid OCH prevents insulitis and diabetes in NOD mice.
AB  - Non-obese diabetic (NOD) mice develop diabetes mediated by pathogenic T-helper
      type 1 (Th1) cells. V alpha 14 Natural killer (NKT) cells are a unique lymphocyte
      subtype implicated in the regulation of autoimmunity and a good source of
      protective Th2 cytokines. We recently developed a Th2-skewing NKT cell ligand,
      OCH. OCH, a sphingosine truncated derivative of alpha-galactosylceramide (alpha
      GC), stimulates NKT cells to selectively produce Th2 cytokines. Here we show that
      OCH prevented the development of diabetes and insulitis in NOD mice. The
      suppression of insulitis by OCH was more profound compared to alpha-GC.
      Infiltration of T cells, B cells and macrophages into islets is inhibited in OCH
      treated NOD mice. OCH-mediated suppression of diabetes is associated with Th2
      bias of anti-islet antigen response and increased IL-10 producing cells among
      islet-infiltrating leukocytes. Considering the non-polymorphic and well conserved
      features of the CD1d molecule in mice and humans, these findings not only support
      the proposed role of NKT cells in the regulation of self-tolerance but also
      highlight the potential use of OCH for therapeutic intervention in type I
      diabetes.

PMID- 15571924
TI  - Cytokines activate caspase-3 in insulinoma cells of diabetes-prone NOD mice
      directly and via upregulation of Fas.
AB  - In type 1 diabetes, autoimmune inflammation of pancreatic islets of Langerhans
      ('insulitis') results in destruction of insulin-producing beta cells. Cytokines
      released from islet-infiltrating mononuclear cells are known to be cytotoxic both
      directly and by upregulating Fas for FasL-induced apoptosis. To investigate the
      role of caspase-3, a major effector of apoptosis in beta-cell death, we asked
      whether cytokine- and/or FasL-induced apoptosis was associated with increased
      activity of caspase-3 in NIT-1 insulinoma cells and islets of autoimmune diabetes
      prone NOD mice. Measurement of caspase-3 activity using a fluorogenic cleavage
      assay was validated in NOD mouse thymocytes undergoing dexamethasone (Dex)
      induced apoptosis. For cytokine-induced apoptosis, NIT-1 cells or islets were
      exposed to IL-1 beta and IFN-gamma for 24 h. Caspase-3-like activity was
      increased 2.1+/-0.7 and 2.4+/-0.9-fold in lysates of cytokine-treated NIT-1 cells
      and NOD mouse islets, respectively. However, NIT-1 cells exhibited 2.1% (4.7 pg
      active caspase-3/microg protein) and islets 0.8% (1.9 pg active caspase-3/microg
      protein) of the active caspase-3 content observed in Dex-treated thymocytes
      (225.1 pg active caspase-3/microg protein). After 24 h cytokine-exposure, the
      percentage of Fas-positive NIT-1 cells increased from 1.4+/-1.1 to 29.7+/-11.6%.
      Addition of FasL for a further 3 h increased caspase-3-like activity an
      additional 1.8-fold in cytokine-treated NIT-1 cells. In summary, exposure of NOD
      mouse insulinoma cells or islets to IL-1 beta and IFN-gamma for 24 h induced
      caspase-3-like activity that, in the case of insulinoma cells at least, can be
      further enhanced by interaction of cytokine-induced Fas receptor with FasL.
      Compared to thymocytes, insulinoma cells and islets from NOD mice were
      characterised by low basal and cytokine-induced caspase-3 activity.

PMID- 15571925
TI  - Gene expression profiling in type 1 diabetes prone NOD mice immunized with a
      disease protective autoantigenic peptide.
AB  - Immunization with autoantigenic peptides skews T cell responses in type 1
      diabetes (T1D), yet the gene-expression signature characterizing this change is
      unclear. We used cDNA microarray technology to identify genes differentially
      regulated in splenocytes of T1D prone NOD mice after immunization with a disease
      protective glutamic acid decarboxylase 65 (GAD(65) P14) peptide. We identified 96
      genes involved in cytokine secretion, humoral immune response, T cell activation,
      signal transduction, cell proliferation, complement activation and inflammatory
      responses. Up-regulation of seven chemokine and cytokine genes confirmed our
      previous findings of increased interferon-gamma (IFN-gamma) secretion, which may
      lead to a protective response in T1D. Hierarchical clustering was used to
      organize treated and control groups on the basis of their overall similarity in
      gene-expression patterns, suggesting association or co-regulation. Semi
      quantitative RT-PCR was used to confirm the expression of selected genes in
      spleen and pancreatic draining lymph nodes. These findings can be used to compare
      other immunization strategies affecting the expression of these genes and explore
      their mechanisms of action. This microarray-based study, thus, unravels the
      molecular mechanism of beta-cell associated autoantigenic peptide immunization in
      T1D prone NOD mice, paving the way for identification of diagnostic markers and
      drug targets for modulating immune responses in T1D.

PMID- 15571926
TI  - The effect of the phytoestrogen coumestrol on the NZB/W F1 murine model of
      systemic lupus.
AB  - Coumestrol is a naturally occurring plant estrogen. As estrogen influences
      cellular and humoral immunity, and has known effects on murine models of lupus,
      we investigated the effect of coumestrol on disease expression in the NZB/W F1
      mouse. Female NZB/W F1 mice were fed a "standard" rodent diet including soy
      proteins, a non-soy diet, or a non-soy diet with 0.01% coumestrol. Outcome
      measures included survival, autoantibody expression, immunoglobulin levels,
      proteinuria, renal histology and B cell immunohistochemistry, and renal mRNA
      expression. At 24 weeks, the treatment group had decreased prevalence of
      autoantibodies detected by immunofluorescence and less splenomegaly. At 39 weeks,
      the prevalence of autoantibodies was similar but the treatment group had less
      proteinuria. Overall, there was little effect of treatment on renal mRNA levels
      as assessed by gene array analysis, but functional ontology mapping revealed that
      genes encoding proteins involved in the immune response were most often affected.
      These results suggest that treatment with coumestrol may ameliorate some aspects
      of disease progression in this model of systemic autoimmunity.

PMID- 15571927
TI  - IgM monomers accelerate disease manifestations in autoimmune-prone Fas-deficient
      mice.
AB  - The monomeric form of IgM, also known as low molecular weight IgM, is found in
      increased concentrations in patients chronically infected with a variety of viral
      and bacterial pathogens or suffering from various autoimmune diseases. Whether
      monomeric IgM contributes to the disease process, however, is not known. To
      address this question, transgenic mice were created that secreted elevated levels
      of IgM monomers. In normal mice (C57BL/6), the presence of IgM monomers did not
      alter the composition of the immune system significantly: lymphocyte subsets and
      serum antibody levels were normal, with the exception of increased levels of IgM
      due to the presence of the monomers. Immune responses also appeared to be normal.
      Transgenic mice did develop antinuclear antibodies (ANA) earlier than non
      transgenic littermates, but did not develop further indications of autoimmune
      disease. When the transgene was expressed in the autoimmune-prone strain of mice,
      B6.MRL-Tnfrsf6(lpr) (B6/lpr), these mice developed autoimmune manifestations more
      rapidly than non-transgenic littermates, including hypergammaglobulinemia,
      splenomegaly, and ANA production. Transgenic mice also displayed earlier evidence
      of immune complex deposition in the kidneys. From these results, we conclude that
      monomeric IgM does not induce autoimmune disease, but its presence can accelerate
      the onset of autoimmune manifestations in otherwise autoimmune prone animals.

PMID- 15571928
TI  - Differences in human antioxidized LDL autoantibodies in patients with stable and
      unstable angina.
AB  - BACKGROUND: Autoantibodies to oxidized LDL (anti-oxLDL) have been found in the
      serum of patients with coronary artery disease (CAD). This study was designed to
      compare the differences in anti-oxLDL titers and isotypes in unstable and stable
      angina patients and to correlate these results with known markers of active
      inflammation in CAD. METHODS: Thirty patients from a tertiary referral general
      hospital with documented CAD were studied. Anti-oxLDL IgG titers and its
      isotypes, high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA)
      were measured. RESULTS: The anti-oxLDL IgG titer was lower (p=0.03) in the
      unstable angina group compared to the stable angina patients (0.084+/-0.102 OD
      versus 0.195+/-0.149 OD, respectively). The predominant IgG isotype in both
      groups was IgG2. IgG4 was significantly higher (0.270+/-0.146 OD, p=0.04) in the
      unstable angina group versus patients with stable angina (0.198+/-0.019 OD).
      There was a significant inverse correlation between anti-oxLDL and hsCRP and SAA
      in this sample population (R=0.37, p<0.05 and R=0.36, p<0.05, respectively).
      CONCLUSION: Patients with unstable angina have lower levels of anti-oxLDL IgG in
      the acute setting of CAD. Plaque instabilization does not seem to acutely modify
      the isotype subsets of anti-oxLDL IgG in these patients.

PMID- 15571929
TI  - Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary
      syndrome further links autoimmunity to cardiovascular disease.
AB  - Anti-apolipoprotein A-1 (Apo A-1) autoantibodies were described in autoimmune
      disorders such as systemic lupus erythematosus (SLE) and antiphospholipid
      syndrome (APS) and might be involved in the genesis of arterial and venous
      thrombotic events. To investigate the presence of these autoantibodies in
      patients with acute coronary syndrome (ACS) without other features of
      autoimmunity, we set up an enzyme-linked immunosorbent assay (ELISA) for anti-Apo
      A-1 antibodies. We used it to investigate their prevalence in ACS as compared to
      SLE and APS and correlated them to plasma Apo A-1 and serum amyloid A protein
      (SAA) concentrations. The prevalence of anti-Apo A-1 autoantibodies in the
      healthy control group was 1% (1/92), but was significantly higher in other
      groups: 21% (11/53) in ACS group (P=0.001), 13% (12/92) in SLE and/or APS group
      (P=0.005). Multiple linear regression revealed a significant correlation between
      plasma Apo A-1 (r=-0.72, P=0.013), plasma SAA concentration (r=0.76, P=0.0066)
      and anti-Apo A-1 IgG titre in ACS patients. The presence of anti-Apo A-1
      autoantibodies in patients with ACS highlights an additional link between
      autoimmunity, inflammation and atherosclerosis.

PMID- 15571930
TI  - IA-2 antibody epitopes and isotypes during the prediabetic process in siblings of
      children with type 1 diabetes.
AB  - To characterize the humoral immune response to the protein tyrosine phosphatase
      (PTP)-like autoantigen (IA-2) in preclinical type 1 diabetes (T1D), and to assess
      the utility of epitope and isotype-specific IA-2 antibody responses as surrogate
      markers for disease development, we analyzed these antibodies in 34 initially non
      diabetic siblings of affected children derived from the "Childhood Diabetes in
      Finland" (DiMe) Study. Half of them presented with T1D during an average
      observation period of 8.7 years. Radiobinding assays were used to determine IA
      2/IA-2 beta epitope-specific (the juxtamembrane region, JM; the PTP-like and the
      beta PTP-like domain) antibodies and isotype-specific (IgG1-4, IgA, IgE and IgM)
      IA-2 antibodies. Initially, 30 of the 34 siblings tested positive for epitope
      specific antibodies. The siblings who progressed to clinical diabetes had IA-2 JM
      antibodies more often (P<0.05) but IgE-IA-2 antibodies less frequently (P<0.05)
      than the siblings who did not progress to T1D. During the identical follow-up
      time, the non-progressors had higher integrated titers of IgE-IA-2 antibodies
      (P=0.05). The occurrence of IgE-IA-2 antibodies was protective, since despite IA
      2 JM antibodies, children with IgE-IA-2 antibodies did rarely progress to T1D.
      This study demonstrates that JM-reactive IA-2 antibodies are associated with an
      increased risk of progression to overt T1D, whereas an IgE response to IA-2
      confers relative protection against clinical disease.

PMID- 15571931
TI  - Decreased DAP12 expression in natural killer lymphocytes from patients with
      systemic lupus erythematosus is associated with increased transcript mutations.
AB  - Decreased numbers of natural killer (NK) cells and impaired NK function have been
      reported in patients with systemic lupus erythematosus (SLE). Since DAP12 plays a
      pivotal role in activation of NK cells, we analyzed the expressions of DAP12
      protein and mRNA in peripheral blood NK cells from patients with SLE. Both DAP12
      protein and mRNA expressions in NK cells from the SLE patients were decreased
      compared with those in NK cells from normal subjects. Sequence analysis of DAP12
      cDNA showed increased nucleotide mutations, including both nucleotide
      substitutions and deletions. In spite of the mRNA mutations, we found no
      mutations in genomic DNA, suggesting that mRNA was modified during or after
      transcription. Decreased expression of DAP12 in NK cells from the patients was
      accompanied by increased expression of ADAR1 (adenosine deaminase that acts on
      RNA transcripts) and by decreased expression of NKp44. These results suggest that
      abnormal expression of DAP12 molecules in NK cells may account for the impairment
      of NK cell function in patients with SLE.

PMID- 15571932
TI  - IL-10 production in B cells is confined to CD154+ cells in patients with systemic
      lupus erythematosus.
AB  - The immunological hallmark of SLE is B cell hyperactivity. CD154 (CD40-L) is
      normally expressed in activated T cells, and plays an important role in T-B
      interactions. Its expression is increased in SLE T cells. Additionally, its
      expression on B cells leads to the development of SLE-like disease in a
      transgenic model. IL-10 is a key cytokine in the disturbed SLE immune system. The
      aim of this work was to explore the relation between IL-10 and CD154 expression
      in SLE B cells. We studied 11 SLE patients and 10 healthy volunteers. Mononuclear
      cells were isolated from peripheral blood and cultured in the presence or absence
      of Cowan I Strain Staphylococcus (CSS). Surface CD154 and intracytoplasmic IL-10
      expression were quantified with flow cytometry. In basal conditions, CD154
      expression was not different in patients and controls. B cell stimulation did not
      cause a significant increase in CD154 expression in control B cells. However, its
      expression increased 2 times in B cells obtained from SLE patients. IL-10
      expression was confined to CD154(+) cells. Our results show that IL-10 production
      is intimately linked to CD154 expression in B cells, and that the IL
      10(+)CD154(+) B cell subset increases abnormally when SLE-derived cells are
      stimulated with CSS.

PMID- 15571934
TI  - Nutrition in critically ill adults: key processes and outcomes.
AB  - Malnutrition is a common problem that can have serious consequences for the
      already compromised critically ill adult. Nurses are often challenged to quantify
      the risk or degree of malnutrition, identify the amount or type of support
      needed, or measure the effectiveness of nutritional intervention. This article
      focuses on key processes used to provide nutrition therapy to critically ill
      adults. These processes and how nurses employ them have the greatest potential
      impact on outcomes related to nutrition in critically ill adults.

PMID- 15571935
TI  - The metabolic response to stress: a case of complex nutrition support management.
AB  - The ICU patient with burns, neurotrauma, sepsis, or major surgery typifies the
      classic hypermetabolic patient. These patients have increased energy and nutrient
      needs as a result of their injuries and require early nutrition support. Although
      these patients are likely to benefit from nutritional intervention, the
      complexity of the stress response to injury and subsequent changes in nutrient
      metabolism make the design and implementation of nutrition care challenging. This
      article reviews the pathophysiology of common hypermetabolic conditions and
      provides strategies to manage the complications associated with nutrition
      support.

PMID- 15571936
TI  - Gastric intubation: assessment and intervention.
AB  - When gastric intubation is the chosen method of providing enteral nutrition, a
      variety of factors must be considered. To choose the proper tube, whether it
      resides in the gastric area or is postpyloric, it is important to consider the
      patient's level of consciousness, the duration of feeding, and the patient's
      overall status. Proper assessment, confirmation of tube placement, and nursing
      vigilance greatly reduce the likelihood of complications.

PMID- 15571937
TI  - Meeting the nutritional needs of the bariatric patient in acute care.
AB  - Meeting the nutritional needs of the bariatric (severely obese) patient in acute
      and critical care can be a challenge. Assessment of metabolic needs and energy
      expenditure is imperative to calculate nutritional needs. Achieving adequate
      nutrition is a result of multidisciplinary team collaboration, with the nurse
      providing important data for the dietitian to calculate needs. This article
      reviews aspects of nutritional support of the bariatric patient including
      assessment, planning, implementation, and evaluation.

PMID- 15571938
TI  - Food and drug interactions in critically ill adults.
AB  - What happens when two needed therapies collide in the critically ill patient?
      This article explores the negative interaction of food and drugs that can occur
      along with important nursing implications. Also included is a discussion on the
      development of a food-drug interaction program, a multifaceted and comprehensive
      approach to monitoring, evaluating, reporting, and reducing the occurrence of
      food-drug interactions.

PMID- 15571939
TI  - Nutritional status: assessing and understanding its value in the critical care
      setting.
AB  - The nutritional assessment is a key determinant in establishing risk for
      malnutrition and is also valuable in predicting outcomes in the critical care
      setting. Studies have demonstrated that nurses who are aware of the impact of
      nutrition and have operational aptitude can influence patient outcomes through
      early intervention. This intervention can result in shortened recovery time and
      decreased lengths of stay. Knowledge of nutrition's effect in the acute and
      critically ill patient is integral for nursing to predict and promote outcomes
      successfully in the critical care setting.

PMID- 15571940
TI  - Eating disorder emergencies: understanding the medical complexities of the
      hospitalized eating disordered patient.
AB  - Eating disorders are maladaptive eating behaviors that typically develop in
      adolescence and early adulthood. Psychiatric maladies and comorbid conditions,
      especially insulin-dependent diabetes mellitus, frequently co-exist with eating
      disorders. Serious medical complications affecting all organs and tissues can
      develop and result in numerous emergent hospitalizations. This article reviews
      the pathophysiologies of anorexia nervosa, bulimia nervosa, and orthorexia
      nervosa and discusses the complexities associated with the treatment of medical
      complications seen in these patients.

PMID- 15571941
TI  - Malnutrition and the critically ill elderly patient.
AB  - Patients over the age of 65 years are the most rapidly growing segment of the
      critical care population, occupying about two thirds of all ICU beds. The
      critical care nurse must have an acute awareness of the nutritional requirements
      and the physiologic impact of age and the stress of illness on the nutritional
      status of the elderly critically ill patient. This knowledge is essential to
      implement appropriate nutritional support to prevent or manage malnutrition.
      Adequate nutritional screening and interventions have been demonstrated to be
      cost effective, resulting in fewer complications, faster recovery, shorter
      hospital stays, and reduced hospital expenditures.

PMID- 15571942
TI  - Benefits and methods of achieving strict glycemic control in the ICU.
AB  - Hyperglycemia, a frequent complication in critically ill patients, has been shown
      to have a negative influence on morbidity and mortality. Many factors contribute
      to hyperglycemia, including the stress response, diabetes, obesity, advanced age,
      corticosteroids, sepsis, pancreatitis, and the use of nutrition support.
      Application of intensive insulin therapy, when compared with conventional
      glycemic control measures, seems to improve outcomes in the critically ill
      patient. Therefore, effective insulin therapy along with appropriate nutrition
      support prescriptions provide a means for the critical care nurse and other
      health care team members to lower complications and enhance recovery in the ICU
      setting.

PMID- 15571943
TI  - Clostridium difficile: causes and interventions.
AB  - Human infection with Clostridium difficile can take many forms. It can exist in
      many patients who are relatively well or who have symptoms similar to irritable
      bowel syndrome. It can also infect the patient in the acute care facility. These
      patients typically have received antibiotics for more than 3 days and begin to
      experience foul-smelling, watery stools within a few days of initiation of
      antibiotic coverage. Good hand washing and environmental cleanliness remain the
      primary ways of preventing the spread of this infection from patient to patient.
      The possibility of using probiotics to replace the beneficial bacteria should be
      pursued.

PMID- 15571944
TI  - Complications of weight loss surgery: implications for critical care nursing.
AB  - Weight-loss surgery (WLS) patients present a relatively new population for the
      health care system. Lack of clinical information about the WLS patient and the
      postoperative WLS patient can negatively affect quality of care and put the
      patient at unnecessary risk. Postoperatively, the bariatric patient is often
      admitted with complex care management requirements that differ from those of
      other surgical patients. Acute and critical care nurses must have a thorough
      understanding of the health implications of obesity, be familiar with common WLS
      procedures, and remain vigilant regarding the potential postoperative
      complications that can occur in this particular patient population.

PMID- 15571945
TI  - Nutritional support in the critically injured.
AB  - Nutritional support must be an integral part of the management of trauma victims.
      This article compares the stress response, a maladaptive response, and
      starvation, an adaptive process, examines the clinical research regarding total
      parenteral nutrition and total enteral nutrition, provides an evidence-based
      approach to initiating nutritional support in critically injured patients, and
      discusses considerations in selecting nutritional formulas.

PMID- 15571946
TI  - MYCN amplification remains prognostically strong 20 years after its "clinical
      debut".

PMID- 15571947
TI  - Hepatic veno-occlusive disease and portal vein thrombosis; closer than we think?

PMID- 15571948
TI  - EACR-18: the best of European cancer research.
AB  - EACR-18 was the 18th biennial meeting of the European Association for Cancer
      Research (EACR). It attracted more than 700 delegates, providing a pivotal
      European forum for basic scientists, translational researchers and clinical
      oncologists alike. It covered most of the key areas and recent developments in
      cancer research. This Review presents a meeting report.

PMID- 15571949
TI  - Portal vein thrombosis during antineoplastic chemotherapy in children: report of
      five cases and review of the literature.
AB  - We report five paediatric cases of portal vein thrombosis (PVT) occurring during
      chemotherapy, observed in two institutions over an 8-year time period. These
      children aged 2.5-15 years were treated for Burkitt's lymphoma, Ewing's tumour,
      small cell bone tumour or medulloblastoma. PVT was diagnosed on colour Doppler
      ultrasonography (US). In four patients, thrombosis occurred 2-45 days after
      severe hepatic veno-occlusive disease (HVOD) secondary to intensive chemotherapy
      containing busulfan. In one case, PVT occurred in the absence of HVOD in a
      patient with pre-existing periportal lymphomatous infiltration. Four patients
      experienced persistent portal hypertension, which resulted in death in one. PVT
      during chemotherapy in children is a rare event and appears to be closely related
      to intensive chemotherapy containing busulfan and to be associated with HVOD.

PMID- 15571950
TI  - Molecular portraits of breast cancer: tumour subtypes as distinct disease
      entities.
AB  - This Review describes advances in the characterisation of breast tumour
      phenotypes using DNA microarrays and the identification of five subtypes of
      breast cancer with significant clinical implications.

PMID- 15571951
TI  - Marine pharmacology in 2001-2: antitumour and cytotoxic compounds.
AB  - During 2001 and 2002, marine antitumour pharmacology research aimed at the
      discovery of novel antitumour agents was published in 175 peer-reviewed articles.
      The purpose of this paper is to present a structured Review of the antitumour and
      cytotoxic properties of 97 marine natural products, many of them novel compounds
      that belong to diverse structural classes, including polyketides, terpenes,
      steroids, and peptides. The organisms yielding these bioactive compounds comprise
      a taxonomically diverse group of marine invertebrate animals, algae, fungi and
      bacteria. Antitumour pharmacological studies were conducted with 30 structurally
      characterised natural marine products in a number of experimental and clinical
      models which further defined their mechanisms of action. Particularly potent in
      vitro cytotoxicity data generated with murine and human tumour cell lines was
      reported for 67 novel marine chemicals with as yet undetermined mechanisms of
      action. Noteworthy, is the fact that marine anticancer research was sustained by
      a collaborative effort, involving researchers from Australia, Brazil, Canada,
      Denmark, Egypt, France, Germany, Italy, Japan, Netherlands, New Zealand, The
      Philippines, Russia, Singapore, South Korea, Thailand, Taiwan, Turkey, Spain,
      Switzerland, Taiwan, Thailand, Turkey, and the United States. Finally, this 2001
      2 overview of the marine pharmacology literature highlights the fact that the
      discovery of novel marine antitumour agents has continued at the same pace as
      during 1998, 1999 and 2000.

PMID- 15571952
TI  - Contraception for teenagers and young adults with cancer.
AB  - Adolescence can be an extremely stressful time for all concerned. When this
      period is then compounded by the development of cancer, formidable and seemingly
      insurmountable problems may be perceived. Cancer in adolescence is relatively
      uncommon, with an annual incidence rate in western populations of approximately
      150-200 per million. Five-year survival of patients diagnosed around 1990
      exceeded 70% in the United Kingdom (UK) and United States of America (USA), and
      adolescents with cancer are likely to remain fertile. Further advances in
      therapeutic modalities are creating a generation of adolescents and young adults
      with cancer who can now aspire to the same sexual and reproductive activities as
      their healthy peers. This then raises the issue of avoidance of undesired
      pregnancy during and after treatment. This article aims to address the
      contraceptive needs of adolescents and young adults undergoing treatment for
      cancer.

PMID- 15571953
TI  - Loss of tight junction plaque molecules in breast cancer tissues is associated
      with a poor prognosis in patients with breast cancer.
AB  - The aim of this study was to investigate the expression of Zonula Occludens (ZO)
      proteins ZO-1, ZO-2 and ZO-3, and MUPP-1 (multi-PDZ domain protein 1),
      peripheral/plaque proteins that function in maintaining tight junction integrity
      and in transducing regulatory signalling events in patients with primary breast
      cancer. Breast cancer primary tumours (n=114) and background tissues (n=30) were
      processed for quantitative-polymerase chain reaction (PCR) analysis, Western
      blotting and immunostaining. Standardised transcript levels of ZO-1 and MUPP-1
      were significantly lower in patients with metastatic disease compared with those
      remaining disease-free (DF) (median follow-up 72.2 months). Immunohistochemistry
      confirmed these results, with decreased levels in ZO-1 staining. For both ZO-1
      and ZO-3, staining was confined to the intercellular regions in normal tissue,
      whereas in tumour tissues staining was diffuse and cytosolic. Q-PCR revealed a
      reduction in the levels of ZO-1 and MUPP-1 in patients with disease recurrence.
      Prognostic indicators of breast cancer were also inversely correlated with ZO-1
      expression. We conclude that low levels of tight junction plaque molecules, such
      as ZO-1 and MUPP-1, in breast cancer are associated with poor patients prognosis.

PMID- 15571954
TI  - The relevance of intraventricular chemotherapy for leptomeningeal metastasis in
      breast cancer: a randomised study.
AB  - To assess the benefit of intraventricular chemotherapy, patients with
      leptomeningeal metastasis (LM) from breast cancer were randomised to treatment
      including intraventricular (IT) chemotherapy (n=17) or to non-intrathecal (non
      IT) treatment (n=18). Appropriate systemic therapy and involved field radiation
      therapy (RT) were given in both arms. Intention-to-treat analysis showed
      neurological improvement or stabilisation in 59% of the IT and in 67% of the non
      IT group, with median time to progression of 23 weeks (IT) and 24 weeks (non-IT).
      Median survival of IT patients was 18.3 weeks and 30.3 weeks for non-IT patients
      (difference 12.9 weeks; 95% Confidence Interval (CI) -5.5 to +34.3 weeks;
      P=0.32). Neurological complications of treatment occurred in 47% (IT) vs 6% (non
      IT) (P=0.0072). In conclusion, standard systemic chemotherapy with involved field
      RT for LM from breast cancer is feasible. Addition of intraventricular
      chemotherapy does not lead to survival benefit or improved neurological response,
      and is associated with an increased risk of neurotoxicity.

PMID- 15571955
TI  - Molecular biomarkers and site of first recurrence after radiotherapy for head and
      neck cancer.
AB  - The prognostic significance of a panel of molecular biomarkers in head and neck
      squamous cell carcinoma (HNSCC) for first failure site (primary (T), nodal (N) or
      distant (M)) was analysed in 309 patients randomised to continuous
      hyperfractionated accelerated radiotherapy (CHART) vs. conventionally
      fractionated radiotherapy. Multivariate competing risks analysis was performed
      using an accelerated failure-time model. First-order interactions between each
      marker and trial arm were also tested. Bcl2-positivity increased the time to T-
      and N-failures, increasing cyclin D1 score decreased the time to N-failures. A
      random proliferative pattern and low Ki-67 decreased the time to M-failures. A
      high CD31 score was associated with a significantly longer time to T-failure
      after CHART, but not after conventional fractionation. Risks of T-, N- and M
      failures could be estimated for individual patients. Competing risks analysis of
      failure sites allows the rational selection of patients for more aggressive loco
      regional or systemic therapy.

PMID- 15571956
TI  - Anastrozole demonstrates clinical and biological effectiveness in oestrogen
      receptor-positive breast cancers, irrespective of the erbB2 status.
AB  - Overexpression of erbB2 in breast tumours can predict resistance to tamoxifen
      therapy. We conducted a small trial to determine if erbB2 status correlates with
      tumour response and biochemical changes in postmenopausal women receiving
      neoadjuvant therapy with the aromatase inhibitor, anastrozole. Twenty-four
      postmenopausal women with oestrogen receptor (ER)-rich, large, operable breast
      tumours received three months of neoadjuvant anastrozole, 1 or 10 mg daily, then
      surgery, followed by another five years of anastrozole 1 mg daily. Response to
      the treatment was based on changes in clinical and ultrasound measurements of
      tumour volume and changes in tumour proliferation and progesterone receptor (PgR)
      status. After follow-up for a median duration of four years therapy, there was no
      apparent difference between erbB2 0/1+ and erbB2 3+ tumours in clinical response
      or changes in proliferation and PgR expression. In conclusion, anastrozole
      appears to be an effective endocrine option in this patient population,
      irrespective of the erbB2 status.

PMID- 15571957
TI  - Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or
      loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC
      New Drug Development Group study.
AB  - The purpose of this study was to evaluate the activity and safety of OSI-211, the
      liposomal form of lurtotecan, in patients ineligible for curative surgery or
      radiotherapy and with metastatic/locoregional recurrent squamous cell carcinoma
      of the head and neck (SCCHN) and target lesions either within a previously
      irradiated field ("within") or outside a previously irradiated field ("outside").
      OSI-211 was given intravenously over 30 min on days 1 and 8 at 2.4 mg/m2/day,
      repeated every 21 days (1 cycle). From July 2001 to March 2002, 32 patients from
      14 institutions were enrolled in the "within" arm and 18 in the "outside" arm. In
      the "within" arm, two patients were ineligible because their tumour site was not
      allowed in the protocol (nasopharynx, skin) and two other patients never started
      treatment. Of the 46 eligible patients who started treatment, there was one
      objective response (response rate: 2.2% (95% Confidence Interval (CI): [0
      11.5%]). Twelve patients in the "within" arm and 6 in the "outside" arm had
      stable disease, with a median duration of 18 weeks, 95% CI (12.7-25.7). The
      median time to progression was 6 weeks (95%CI: [5.9-12.7] weeks). Haematological
      toxicity was moderate in both arms. The most common haematological toxicity was
      grade 1-2 anaemia in 79% of patients. Non-haematological toxicity was mild in
      both arms. The most common grade 3-4 non-haematological toxicity was infection in
      8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well
      tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN.

PMID- 15571958
TI  - MYCN-status in neuroblastoma: characteristics of tumours showing amplification,
      gain, and non-amplification.
AB  - While the role of MYCN-amplification (MNA) for risk assessment in neuroblastoma
      is undisputed, the phenomenon of gene copy excess below the amplification
      threshold is rarely described. To discuss biological characteristics and the
      clinical impact of the so-called MYCN-gain versus amplified or non-amplified
      cases, we investigated the MYCN status of 659 patients uniformly analysed by
      fluorescence in situ hybridisation. The number of MYCN-amplified tumours in our
      cohort was 18% (116/659); an additional 38 tumours (6%) displayed MYCN-gain. Both
      alterations were associated with an advanced stage disease, an increased patient
      age and further chromosomal alterations. Most of the amplified neuroblastomas
      displayed 1p aberrations, whereas MYCN-gain tumours correlated with 11q
      alterations. In contrast to the amplified cases, tumours with gain displayed no
      increased MYCN RNA levels. MNA versus non-amplification discriminated between
      good and poor outcomes, independent of stage, age and the degree of
      amplification. However, patients with amplified tumours showed a significantly
      better outcome when this was combined with non-stage 4 disease and age <1 year
      versus stage 4 and age < 1 year. Although MYCN-gain was associated with poor
      event-free-survival (EFS) in stages 1-3, 4S (P=0.005), this might be related to
      associated genetic aberrations and not to the MYCN-gain itself. A survival
      difference between neuroblastomas with gain and single copy MYCN could not be
      delineated. In conclusion, MNA predicts a poor outcome for neuroblastoma patients
      of all stages and age. MYCN-gain is also a characteristic feature of advanced
      stage tumours and older patients, but is not associated with higher MYCN
      expression and appears not to be discriminative in predicting patient outcome.

PMID- 15571959
TI  - Further clues concerning the aetiology of childhood central nervous system
      tumours.
AB  - Previously, we reported space-time clustering and seasonal variation in childhood
      central nervous system (CNS) tumours for the period 1954-1998. These previous
      studies provided evidence that infections may be involved in aetiology. To
      determine whether there were also localised spatial factors involved in aetiology
      we analysed the geographical distribution of CNS tumours in children aged 0-14
      years using Manchester Children's Tumour Registry (MCTR) data for the period 1976
      2000. Specifically, the Potthoff-Whittinghill test for spatial clustering was
      applied and Poisson regression was used to analyse the relationship between
      incidence rates and small-area population density, ethnic composition and
      deprivation index. No relationships were seen for all CNS tumours together and
      only a few for the subgroups. The previous findings of space-time clustering and
      seasonal variation, involving astrocytoma and ependymoma, together with the lack
      of spatial clustering and ecological relationships for these tumours provide
      evidence that astrocytoma and ependymoma may be associated with a highly mobile
      transient aetiological agent. An example of such an agent is an infection that
      occurs in mini-epidemics.

PMID- 15571960
TI  - The importance of assessing the readiness to change sun-protection behaviours: a
      population-based study.
AB  - The purpose of this study was to collect information that may be valuable in
      developing successful skin cancer prevention programmes. A random sample of 6000
      adolescents and 4000 adults answered a questionnaire about sun-related issues.
      The response rate was 68%. Using sunscreen was the main sun-protection behaviour
      measured. Approximately 40% of adolescents and 30% of adults did not use any sun
      protection strategy other than sunscreen. Readiness to change sun-protection
      behaviour was measured by assessing the stages of change modified from the
      Transtheoretical Model (TTM). Half of the participants were in the
      precontemplation stage of giving up sunbathing and avoiding the sun between 11
      a.m. and 3 p.m. Attitude had the strongest association with being in the
      action/maintenance stages for all sun protection behaviours. A large proportion
      of participants were not ready to change their sun-protection behaviours, which
      highlights the importance of including motivational strategies when attempting to
      change sun-protection behaviours.

PMID- 15571961
TI  - Gender and age-related differences in Burkitt lymphoma--epidemiological and
      clinical data from The Netherlands.
AB  - Although Burkitt's lymphoma (BL) is classified as one entity in the World Health
      Organisation (WHO) classification, we wondered whether BL should not be
      considered as a different disease in children compared with adults. Netherlands
      Cancer Registry (NCR) data were obtained from 1994 to 1998 (n=203). Detailed
      clinical data from two treatment protocols were compared: one for adults up to
      the age of 65 years (n=27) and one for children (n=80). All slides of the two
      clinical studies were centrally reviewed which included immunophenotyping and
      when necessary breakpoint analysis of MYC/8q24. Only cases with an unambiguous
      diagnosis of BL (classical and atypical BL) were accepted. The age distribution
      of BL-patients showed a bimodal distribution with a peak at the paediatric age
      and a steady increase after approximately 60 years of age. Most of the patients
      were males (89% for children and 78% for adults) and only male patients showed
      this bimodality. Children more often had extranodal disease (81% vs. 59%),
      whereas adults more often had nodal disease (89% vs. 53%). Based on epidemiology
      and clinical presentation, the concept that BL is one disease should be re
      challenged.

PMID- 15571962
TI  - BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a
      population-based study.
AB  - A single founder mutation in each of the BRCA genes has been identified in
      Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all
      ovarian cancer patients diagnosed over the period 1991-2000 was determined.
      Mutation status was correlated with family history, tumour morphology and age at
      diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours)
      were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2%
      and 6% of cases, respectively. No BRCA mutations were found in the borderline
      tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2
      carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2
      carriers and approximately 14% for non-carriers with carcinoma. In conclusion,
      BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is
      associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A
      mutation is too rare to contribute significantly to ovarian cancer in Iceland.

PMID- 15571963
TI  - Sheep and goats: separating cervix and corpus uteri from imprecisely coded
      uterine cancer deaths, for studies of geographical and temporal variations in
      mortality.
AB  - Analysing time trends in mortality from cancers of the cervix and corpus uteri
      using routine data sources (such as the World Health Organisation mortality
      database) involves two major problems: deaths certified as "uterus, unspecified
      site", and the presence of a combined category comprising unspecified and corpus
      uteri cancer deaths. To avoid misleading interpretations, the unspecified and the
      misclassified data must be incorporated into the analysis to produce rates that
      allow meaningful comparisons between populations and over time. Reallocation
      methods based on age- and time-specific distributions of cervix and corpus uteri
      cancer are applied to the unspecified deaths, while for those in the combined
      category, the age- and time-specific distributions of unspecified and corpus
      uteri cancer are considered. Adjustments of the general strategies for
      reallocation were developed to take into account the different quality of the
      data. Results from eight European countries with different degrees of coding
      precision are presented. The reallocation methods bring the cervix and corpus
      uteri mortality trends more in line with the trends for countries with more
      precise data while keeping the country-specific characteristics. In addition, the
      methods ensured the availability of time trends for corpus uteri cancer in women
      age 50 years and older, which were completely missing without reallocation. We
      propose generally applicable reallocation methods that allow valid time trend
      analysis of cervix and corpus uteri cancer mortality using datasets of varying
      precision. Our results show that any sensible analysis of time trends must
      involve procedures for correcting for unspecified and misclassified uterine
      cancer deaths. The modified data are available at .

PMID- 15571964
TI  - Expression of heat-shock protein Hsp60 correlated with the apoptotic index and
      patient prognosis in human oesophageal squamous cell carcinoma.
AB  - Cellular stress response and apoptosis are two highly conserved mechanisms for
      maintaining homeostasis. Hsp60 and Hsp90 have been shown to play pro- and anti
      apoptotic roles, respectively. Our present study examined whether there is a
      correlation between the expression of Hsp60 and Hsp90, clinical parameters, the
      apoptotic index (AI), and the prognosis of patients with oesophageal squamous
      cell carcinoma (ESCC). We immunohistochemically stained cells for Hsp60, Hsp90,
      and single-stranded DNA (ssDNA), which acts as an apoptotic marker. In normal
      oesophageal epithelium tissue, Hsp60 and Hsp90 were expressed in the cytoplasm
      and membrane from the basal cell layer to the supra-basal cell layers. Hsp60 and
      Hsp90 positive stainings (+) were found in 63 of 123 cases (51%) and 62 of 123
      cases (50%), respectively. There was no correlation between Hsp60 and Hsp90
      expression levels and any of the clinical parameters examined. The five-year
      survival rate for ESCC patients with Hsp60 (+) expression was significantly
      higher than for those patients with Hsp60 (-) expression (P=0.0371). Five-year
      survival rates of patients with Hsp60 (+) and (-) were 49% and 33%, respectively.
      By contrast, Hsp90 expression failed to predict patient prognosis (P=0.7965). The
      high-AI group did not have a significantly better prognosis than the low-AI group
      (P=0.2218). Statistical analysis showed a significant correlation between the
      expression of Hsp60 and AI in ESCC patients (P=0.008). Thus, the five-year
      survival rate for the high-AI/Hsp60 (+) group was statistically significantly
      better than for the other groups (P=0.0281). The results obtained in this study
      indicate that positive Hsp60 expression is a good prognostic indicator. This may
      be due to its role as a chaperone in contributing to the induction of apoptosis.
      These data suggest that Hsp60 expression correlates with the AI and patient
      prognosis in human ESCC.

PMID- 15571965
TI  - Prognostic significance of detecting micrometastases by tyrosinase RT/PCR in
      sentinel lymph node biopsies: lessons from 322 consecutive melanoma patients.
AB  - This prospective study was performed to determine the prognostic value of
      tyrosinase mRNA detection in sentinel lymph nodes (SLN) of melanoma patients.
      About 847 SLNs from 322 consecutive patients were assessed by histopathology and
      immunohistochemistry as well as tyrosinase-reverse transcriptase-polymerase chain
      reaction (RT/PCR) for the presence of micrometastases. The results were
      correlated with the prognostic parameters employing a multivariate analysis after
      a median follow-up of 37 months. Histopathological analysis revealed metastases
      in 34/322 patients (10.6%). Among the 288 patients with histopathologically
      negative SLN, tyrosinase-mRNA was detected in 39 patients. A relapse of the
      tumour occurred in 44.1% of the patients with histopathologically positive SLN,
      in 25.6% with histopathologically negative, but tyrosinase-RT/PCR-positive SLN,
      and 8.0% with "double-negative" SLN. A multivariate analysis identified tumour
      thickness, the histopathological SLN status, and the ulceration of the primary
      tumour as independent prognostic factors. Thus, by assessing tyrosinase mRNA in
      the SLN of melanoma patients, we identified a subgroup with histopathologically
      negative, but Tyr-RT-PCR-positive SLN who have a high risk of disease relapse.

PMID- 15571966
TI  - Methylation analysis of the neurofibromatosis type 1 (NF1) promoter in peripheral
      nerve sheath tumours.
AB  - Peripheral nerve sheath tumours are hallmarks of neurofibromatosis type 1 (NF1).
      Development of plexiform neurofibromas to malignant peripheral nerve sheath
      tumours (MPNST) is common. The NF1 gene promoter harbours a hypomethylated CpG
      island. Thus, methylation changes may be involved in the development of different
      types of neurofibromas and malignant transformation. We investigated NF1
      associated dermal (n=9) and plexiform neurofibromas (n=7), MPNST (n=5) and non
      NF1 leucocyte samples (n=20) for their methylation pattern by bisulphite genomic
      sequencing. We could not find global hypermethylation in the NF1 promoter in our
      series. Nevertheless, site-specific methylation, involving transcription factor
      binding sites for SP1, CRE (-10), and AP-2, was observed. One region of the 5'
      UTR (untranslated region) overlapping with a putative AP-2 binding site was
      methylated at 30-100% in 4/20 control samples. In conclusion, we did not find
      hypermethylation in NF1-associated tumours. Instead, low level methylation could
      parallel a global genomic hypomethylation in malignancy.

PMID- 15571967
TI  - Rapamycin inhibits doxorubicin-induced NF-kappaB/Rel nuclear activity and
      enhances the apoptosis of melanoma cells.
AB  - Inhibition of nuclear factor (NF)-kappaB/Rel can sensitise many tumour cells to
      death-inducing stimuli, including chemotherapeutic agents, and there are data
      suggesting that disruption of NF-kappaB may be of therapeutic interest in
      melanoma. We found that rapamycin sensitised a human melanoma cell line,
      established from a patient, to the cytolytic effects of doxorubicin. Doxorubicin
      is a striking NF-kappaB/Rel-inducer, we therefore investigated if rapamycin
      interfered with the pathway of NF-kappaB/Rel activation, i.e. IkappaBalpha
      phosphorylation, -degradation and NF-kappaB/Rel nuclear translocation, and found
      that the macrolide agent caused a block of IKK kinase activity that was
      responsible for a reduced nuclear translocation of transcription factors. Western
      blots for Bcl-2 and c-IAP1 showed increased levels of these anti-apoptotic
      proteins in cells incubated with doxorubicin, in accordance with NF-kappaB/Rel
      activation, while rapamycin clearly downmodulated these proteins, in line with
      its pro-apoptotic ability. The effect of the macrolide on NF-kappa B/Rel
      induction appeared to be independent of the block in the PI3k/Akt pathway,
      because it could not be reproduced by the phosphatidyl inositol 3 kinase (PI3k)
      inhibitor, wortmannin. Recently, the immunophilin, FKBP51, has been shown to be
      essential for the function of IKK kinase. We found high expression levels of
      FKBP51 in melanoma cells. Moreover, we confirmed the involvement of this
      immunophilin in the control of IKK activity. Indeed, IkappaBalpha could not be
      degraded when FKBP51 was downmodulated by short-interfering RNAs (siRNAs). These
      findings provide a possible mechanism for the downmodulation of NF-kappaB by
      rapamycin, since the macrolide agent specifically inhibits FKBP51 isomerase
      activity. In conclusion, our study demonstrates that rapamycin blocked NF
      kappaB/Rel activation independently of PI3k/Akt inhibition suggesting that the
      macrolide agent could synergise with NF-kappaB-inducing anti-cancer drugs in PTEN
      positive tumours.

PMID- 15571968
TI  - Dual HER 1-2 targeting of hormone-refractory prostate cancer by ZD1839 and
      trastuzumab.
AB  - Epidermal growth factor receptor (EGFR) and HER-2 are associated with a poor
      prognosis in various cancers, including prostate cancer. Inhibition of these
      receptors may provide a treatment for hormone-refractory prostate cancer. The
      presence of HER-2 (Western blot) and EGFR (5830 fmol/mg protein, ligand-binding
      assay) was assessed in the hormone-refractory human prostate cancer cell line, DU
      145. Cells were exposed to the selective EGFR-TKI (EGFR tyrosine kinase
      inhibitor) gefitinib ('Iressa; ZD1839) and/or the HER-2-targeted monoclonal
      antibody trastuzumab ('Herceptin'), for 96 h. Irradiation (RX) at 6 Gy the dose
      causing 50% growth inhibition, was applied 48 h after the start of drug
      treatment. There was a dose-related effect on cell survival for both ZD1839 and
      trastuzumab treatments. Combining ZD1839 and trastuzumab led to less than
      additive effects on cell survival. Chou and Talalay representations further
      characterised this less than additive effect on cell survival. The application of
      ZD1839 led to a marked elevation in the level of the negative regulator of cell
      division, p27. The ZD1839-trastuzumab combination had less of an impact on p27
      expression compared with the effect of ZD1839 treatment alone. The lowest
      expression of the apoptotic-related protein, Bax, was observed in the presence of
      the drug combination. There was a significant interaction (synergism) between RX
      and either ZD1839 or trastuzumab treatments. In contrast, the drug combination
      with RX resulted in antagonistic cytotoxic effects. These results indicate an
      antagonistic interaction between EGFR and HER-2 targeting and provide molecular
      mechanisms supporting this observation. Data from DU-145 cells suggest that dual
      targeting of EGFR and HER-2 may be inappropriate for the treatment of hormone
      refractory prostate cancer, especially in the context of their combination with
      RX.

PMID- 15571969
TI  - Clinical relevance of thymidylate synthase expression in the signet ring cell
      histotype component of colorectal carcinoma.
AB  - Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is
      inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS
      expression and the proliferation rate in the different histological types of
      colorectal carcinoma (CRC). 50 patients with CRC were included in this study and
      evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67.
      20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma
      (SRCCs) and 15 cases were "mixed-type", with at least two different histological
      components. Intestinal and mucinous histotypes were positive for TS and Ki67,
      while "signet ring cell" samples were negative or showed only weak and focal
      positivity for both the TS and Ki67 antibodies. Our results show that signet ring
      cells (that are also often present in intestinal and mucinous carcinomas), are in
      the post-mitotic phase of the cell cycle and show a low proliferation index and
      TS expression. As TS is the key enzyme for DNA synthesis pathways and is
      inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels
      in the different histotypes of CRC could affect the potential responsiveness of
      these tumours to fluoropyrimidine chemotherapy, with a low efficacy being
      expected in signet ring cell areas.

PMID- 15571970
TI  - Noninvasive in vivo whole body luminescent analysis of luciferase labelled
      orthotopic prostate tumours.
AB  - Light photons refracted through living tissues can be used to noninvasively
      monitor the proliferation of cells expressing bioluminescent markers. We
      demonstrate the use of a luminometer for noninvasive in vivo whole body
      luminometric analysis (in vivo WBLA) of luciferase-expressing prostate tumours
      growing orthotopically in nude mice, and thus hidden from visual inspection. In
      this procedure, the intraperitoneally (i.p.) inoculated luciferin, the luciferase
      substrate, reaches the tumours rapidly and the light photons generated by the
      tumour are recorded by placing the anaesthetised mice in the detection chamber of
      a luminometer, over the detector slot. We show that the number of recorded light
      photons is proportional to the tumour mass and to the luciferase activity
      recorded in vitro. The procedure is applied to demonstrate the use of paclitaxel
      as an antineoplasic agent with its well characterised antiproliferative activity.

PMID- 15571971
TI  - The responsiveness of a tumour to any kind of therapy is reflected by the
      objective response rate.

PMID- 15571972
TI  - Clinical potential of minocycline for neurodegenerative disorders.
AB  - Minocycline, an antibiotic of the tetracycline family, has been shown to display
      neurorestorative or neuroprotective properties in various models of
      neurodegenerative diseases. In particular, it has been shown to delay motor
      alterations, inflammation and apoptosis in models of Huntington's disease,
      amyotrophic lateral sclerosis and Parkinson's disease. Despite controversies
      about its efficacy, the relative safety and tolerability of minocycline have led
      to the launching of various clinical trials. The present review summarizes the
      available data supporting the clinical testing of minocycline for these
      neurodegenerative disorders. In addition, we extend our discussion to the
      potential applications of minocycline for combining this treatment with cellular
      and molecular therapy.

PMID- 15571973
TI  - Hemoglobin promotes Abeta oligomer formation and localizes in neurons and amyloid
      deposits.
AB  - The objective of this study was to search for brain-specific binding proteins
      that participated in Abeta aggregation. Immunoprecipitation of Abeta in
      Alzheimer's brain homogenate revealed a major co-precipitating 16-kDa protein
      band, which was identified through mass spectrometry as hemoglobin (Hb) alpha and
      beta chains. Hemoglobin was distributed in Alzheimer's disease (AD) patients in a
      brain region-dependent manner, with the highest levels in the hippocampus and
      parietal gray (PG) matter, followed by parietal white matter (PW), and the lowest
      in cerebellum (Cb). AD parietal gray and white matters exhibited higher Hb levels
      than those in the nondemented (ND) group. Likewise, RT-PCR revealed that the Hb
      mRNA levels in AD inferior temporal gyri were higher than those of ND subjects.
      Furthermore, Hb was shown to promote Abeta oligomer formation.
      Immunohistochemical studies indicated that Hb was localized within the cytosol of
      pyramidal neurons in the hippocampus, suggesting a potential source of
      intracerebral Hb. Finally, double immunofluorescent assay confirmed the co
      localization of Hb with senile plaques (SP) and cerebral amyloid angiopathy
      (CAA). We propose that an elevation in brain Hb via circulation leakage or
      perturbations of Hb gene regulation may participate in AD pathogenesis.

PMID- 15571974
TI  - The impact of excitotoxic blockade on the evolution of injury following combined
      mechanical and hypoxic insults in primary rat neuronal culture.
AB  - Traumatic brain injury (TBI) involves alterations in neuronal physiology, often
      complicated by secondary hypoxic or hypotensive events. Excitotoxicity is an
      important process induced in both TBI and hypoxic or ischemic insults to the
      brain. We investigated two hypotheses: (1) excitotoxicity is more prominent
      following combined mechanical and hypoxic injury than either alone; (2) both AMPA
      and NMDA receptor activation mediate combined mechanical and hypoxic injury.
      Media in primary mixed neuronal cultures were replaced with conditioned media
      containing MK801 (NMDA antagonist) and/or NBQX (AMPA/kainate antagonist).
      Cultures were then subjected to mechanical injury. Afterward, media were
      exchanged for hypoxic media containing the antagonist, and plates were placed in
      hypoxia chambers for 7 h. At 24 h following hypoxia, LDH release, trypan blue
      uptake, and morphologic changes were assessed. Blockade had no effect after
      mechanical injury. After hypoxia, MK801 and combined MK801/NBQX decreased LDH and
      trypan blue to control levels. NBQX alone after hypoxia had less impact. After
      combined mechanical injury and hypoxia, both MK801 and NBQX partially reduced LDH
      and trypan blue. Combining the antagonists led to reduction to control values for
      both endpoints. We conclude that excitotoxic processes are more prominent after
      combined than isolated injuries in neurons and that increased cell death is
      mediated by both NMDA and AMPA receptor activation following combined injuries.

PMID- 15571975
TI  - Temporal patterns of the cerebral inflammatory response in the rat lithium
      pilocarpine model of temporal lobe epilepsy.
AB  - To better understand the role of inflammatory responses in temporal lobe
      epilepsy, we characterized Interleukin1-beta (IL1-beta), Nuclear Factor-kappaB
      (NF-kappaB), and Cyclooxygenase-2 (COX-2) expression together with
      neurodegeneration in the rat lithium-pilocarpine model. The immunohistochemical
      expression of IL1-beta, NF-kappaB, and COX-2 started by 12 h post-injection,
      persisted for 24 h (status epilepticus period), and returned to basal levels by 3
      and 6 days (latent period). The regional distribution of IL1-beta, NF-kappaB, and
      COX-2 occurred mainly in structures prone to develop neuronal damage. Using
      double-staining protocols, we detected IL1-beta expression in glial cells, COX-2
      expression in neurons, and NF-kappaB in both cell types. The presence of Fluoro
      Jade-B-positive degenerating neurons was associated with IL1-beta, NF-kappaB, and
      COX-2 proteins expression during status epilepticus but not during the latent
      period while neurons were still degenerating. These data suggest that seizure
      related IL1-beta, NF-kappaB, and COX-2 expression may contribute to the
      pathophysiology of epilepsy by inducing neuronal death and astrocytic activation.

PMID- 15571976
TI  - Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated
      with profound learning/memory deficits in juveniles followed by progressive
      functional recovery in adults.
AB  - Administration of ethanol to rodents during the synaptogenesis period induces
      extensive apoptotic neurodegeneration in the developing brain. This neurotoxicity
      may explain the reduced brain mass and neurobehavioral disturbances in human
      Fetal Alcohol Syndrome (FAS). Here, we report binge-like exposure of infant mice
      to ethanol on a single postnatal day triggered apoptotic death of neurons from
      diencephalic structures that comprise an extended hippocampal circuit important
      for spatial learning and memory. The ethanol exposure paradigm yielding these
      neuronal losses caused profound impairments in spatial learning and memory at 1
      month of age. This impairment was significantly attenuated during subsequent
      development, indicating recovery of function. Recovery was not associated with
      increased neurogenesis, suggesting plastic reorganization of neuronal networks
      compensated for early neuronal losses. We hypothesize that neuroapoptotic damage
      in homologous regions of human brain underlies cognitive deficits in FAS and the
      human brain of FAS victims has a similar capacity to effect functional recovery.

PMID- 15571977
TI  - Resistance of neurofilaments to degradation, and lack of neuronal death and mossy
      fiber sprouting after kainic acid-induced status epilepticus in the developing
      rat hippocampus.
AB  - Neurofilament (NF) proteins, the major constituent of intermediate filaments in
      neurons, have an important role in cellular stability and plasticity. We have now
      studied the short-term (hours) and long-term (up to 1 week) effects of kainic
      acid (KA)-induced status epilepticus (SE) on the reactivity of NF proteins, and
      mossy fiber (MF) sprouting and neuronal death up to 4 weeks in 9-day-old rats. In
      Western blotting, the expression of the phosphorylation-independent epitopes of
      NF-L, NF-M, and NF-H rapidly but transiently increased after the treatment,
      whereas the phosphorylated NF-M remained elevated for 7 days. However, the
      treatment did not change the immunoreactivity of NF proteins, and no neuronal
      death or mossy fiber sprouting was detected at any time point. Our findings
      indicate seizure-induced reactivity of NF proteins but their resistance to
      degradation, which could be of importance in neuronal survival and may also
      prevent MF sprouting in the developing hippocampus.

PMID- 15571978
TI  - Impaired learning-dependent cortical plasticity in Huntington's disease
      transgenic mice.
AB  - Huntington's disease (HD) is a genetically transmitted neurodegenerative
      disorder. The neuropathology in HD is a selective neuronal cell death in several
      brain regions including cortex. Although changes in synaptic plasticity were
      shown within the hippocampus and striatum of HD transgenic mice, there are no
      studies considering neocortical synaptic plasticity abnormalities in HD. We
      examined the impact of the HD transgene upon learning-dependent plasticity of
      cortical representational maps. The effect of associative learning, in which
      stimulation of a row of vibrissae was paired with appetitive stimulus, upon
      functional representations of vibrissae in the barrel cortex, was investigated
      with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type
      mice, cortical representation of the row of vibrissae involved in the training
      was expanded, while in HD mice the representation of this row was not expanded.
      The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in
      plasticity of primary somatosensory cortex.

PMID- 15571979
TI  - FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3
      nitropropionic acid in rat primary cortical cultures.
AB  - The mitochondrial toxin 3-nitropropionic acid (3-NP) has been largely used to
      study neurodegenerative disorders in which bioenergetic defects are implicated.
      In the present study, we analyzed the molecular pathways involved in FK506
      neuroprotection against cell death induced by 3-NP, using cultured cortical
      neurons. 3-NP induced cytochrome c release and increased caspases -2, -3, -8, and
      -9-like activities, although, calpain activity was not significantly affected.
      FK506 decreased cytochrome c release and caspase-3-like activity induced by 3-NP,
      without changing the activities of other caspases. FK-506 also decreased the
      number of apoptotic neurons, determined by Hoechst. Under these conditions, FK506
      alone significantly reduced calcineurin activity by about 50%. Our results also
      showed a decrease in mitochondrial Bax and an increase in mitochondrial Bcl-2
      levels upon exposure to FK506 and 3-NP. However, no significant changes occurred
      in total Bcl-2 and Bax levels. Altogether, the results suggest that FK506
      neuroprotection against 3-NP-induced apoptosis is associated with the
      redistribution of Bcl-2 and Bax in the mitochondrial membrane.

PMID- 15571980
TI  - Acute exposure to GSM 900-MHz electromagnetic fields induces glial reactivity and
      biochemical modifications in the rat brain.
AB  - The worldwide proliferation of mobile phones raises the question of the effects
      of 900-MHz electromagnetic fields (EMF) on the brain. Using a head-only exposure
      device in the rat, we showed that a 15-min exposure to 900-MHz pulsed microwaves
      at a high brain-averaged power of 6 W/kg induced a strong glial reaction in the
      brain. This effect, which suggests neuronal damage, was particularly pronounced
      in the striatum. Moreover, we observed significant and immediate effects on the
      Kd and Bmax values of N-methyl-D-aspartate (NMDA) and GABA(A) receptors as well
      as on dopamine transporters. Decrease of the amount of NMDA receptors at the
      postsynaptic membrane is also reported. Although we showed that the rat general
      locomotor behavior was not significantly altered on the short term, our results
      provide the first evidence for rapid cellular and molecular alterations in the
      rat brain after an acute exposure to high power GSM (Global System for Mobile
      communication) 900-MHz microwaves.

PMID- 15571981
TI  - Neostriatal and cortical quinolinate levels are increased in early grade
      Huntington's disease.
AB  - Huntington's disease (HD), an inherited neurodegenerative disorder, is caused by
      an abnormal polyglutamine expansion in the huntingtin protein. This genetic
      defect may result in heightened neuronal susceptibility to excitotoxic injury, a
      mechanism that has been postulated to play a critical role in HD. Quinolinate
      (QUIN) and kynurenate (KYNA), two endogenous neuroactive metabolites of the
      kynurenine pathway of tryptophan degradation, have been proposed to modulate
      excitotoxic neuronal death in HD. A third kynurenine pathway metabolite, the free
      radical generator 3-hydroxykynurenine (3-HK), has also been hypothesized to play
      a causal role in the pathogenesis of HD. We show here that the brain levels of
      both 3-HK and QUIN are increased three to four-fold in low-grade (grade 0/1) HD
      brain. These changes were seen in the neocortex and in the neostriatum, but not
      in the cerebellum. In contrast, brain 3-HK and QUIN levels were either unchanged
      or tended to decrease in grade 2 and advanced grade (grades 3-4) HD brain. Brain
      kynurenine and KYNA levels fluctuated only modestly as the illness progressed.
      These results support a possible involvement of 3-HK and QUIN in the early phases
      of HD pathophysiology and indicate novel therapeutic strategies against the
      disease.

PMID- 15571982
TI  - Reduced expression of NO-sensitive guanylyl cyclase in reactive astrocytes of
      Alzheimer disease, Creutzfeldt-Jakob disease, and multiple sclerosis brains.
AB  - In Alzheimer's disease (AD) brains increased NO synthase (NOS) expression is
      found in reactive astrocytes surrounding amyloid plaques. We have recently shown
      that treatment with beta-amyloid peptides or IL-1beta down-regulates NO-sensitive
      soluble guanylyl cyclase (sGC) in cultured astrocytes and in adult rat brain. In
      this work, we have examined sGC activity and expression in postmortem brain
      tissue of AD patients and matched controls. No significant alteration was
      observed in basal or NO-stimulated sGC activity, nor in sGC beta1 and alpha1
      subunit levels in cortical extracts of AD brains. Immunohistochemistry showed
      intense and widespread labeling of sGC beta1 in cortical and hippocampal neurons
      and white matter fibrillar astrocytes, while grey matter astrocytes were faintly
      stained. In AD, expression of sGC in neurons and fibrillar astrocytes is not
      altered but is markedly reduced in reactive astrocytes surrounding amyloid
      plaques. Immunostaining for sGC beta1 was also lacking in reactive astrocytes in
      cortex and subcortical white matter in Creutzfeldt-Jakob disease brains and in
      subacute and chronic plaques in multiple sclerosis (MS) brains. Thus, induction
      of astrocyte reactivity is associated with decreased capacity to generate cGMP in
      response to NO both in vitro and in vivo. This effect may be related to the
      development of the astroglial inflammatory response.

PMID- 15571983
TI  - Chronic temporal lobe epilepsy is associated with severely declined dentate
      neurogenesis in the adult hippocampus.
AB  - While it is clear that acute hippocampal injury or status epilepticus increases
      the production of new neurons in the adult dentate gyrus (DG), the effects of
      chronic epilepsy on dentate neurogenesis are unknown. We hypothesize that
      epileptogenic changes and spontaneous recurrent motor seizures (SRMS) that ensue
      after hippocampal injury or status epilepticus considerably decrease dentate
      neurogenesis. We addressed this issue by quantifying the number of cells that are
      positive for doublecortin (DCX, a marker of new neurons) in the DG of adult F344
      rats at 16 days and 5 months after an intracerebroventricular kainic acid (ICV
      KA) administration or after graded intraperitoneal KA (IP KA) injections, models
      of temporal lobe epilepsy (TLE). At early post-KA administration, the injured
      hippocampus exhibited increased dentate neurogenesis in both models. Conversely,
      at 5 months post-KA administration, the chronically epileptic hippocampus
      demonstrated severely declined neurogenesis, which was associated with
      considerable SRMS in both KA models. Additionally, stem/progenitor cell
      proliferation factors, FGF-2 and IGF-1, were decreased in the chronically
      epileptic hippocampus. Interestingly, the overall decrease in neurogenesis and
      the extent of SRMS were greater in rats receiving IP KA than rats receiving ICV
      KA, suggesting that the extent of neurogenesis during chronic TLE exhibits an
      inverse relationship with SRMS. These results provide novel evidence that chronic
      TLE is associated with extremely declined dentate neurogenesis. As fraction of
      newly born neurons become GABA-ergic interneurons, declined neurogenesis may
      contribute to the increased seizure-susceptibility of the DG in chronic TLE.
      Likewise, the hippocampal-dependent learning and memory deficits observed in
      chronic TLE could be linked at least partially to the declined neurogenesis.

PMID- 15571984
TI  - Hypoxia-induced changes in tight junction permeability of brain capillary
      endothelial cells are associated with IL-1beta and nitric oxide.
AB  - We examined whether hypoxia alone could produce changes in the permeability of
      brain capillary endothelial cells (EC) and whether a stimulation of hypoxic
      status alters the gene expression of occludin and glucose transporter 1 (GLUT1).
      Exposure of EC to hypoxia resulted in increased permeability, with the greatest
      decrease in transendothelial electrical resistance (TER) at 40 h. Moreover,
      hypoxia alone induced the expression of both mRNA in EC. Furthermore, we found
      that interleukin-1 (IL-1)beta, glutamate, hydrogen peroxide (H2O2), and sodium
      nitroprusside (SNP) induced the expression of mRNA for occludin and GULT1 under
      normoxic condition. The decrease in TER due to hypoxia was inhibited on addition
      of an anti-IL1 antibody and nitric oxide synthase (NOS) inhibitor in EC. These
      results indicate that the expression of occludin and GLUT1 mRNA is sensitive to
      exposure to hypoxia and that the changes of permeability in EC are associated
      with IL-1beta and NO.

PMID- 15571985
TI  - Insulin resistance contributes to aberrant stress responses in the Tg2576 mouse
      model of Alzheimer's disease.
AB  - We previously reported aberrant stress responses and impaired glucose tolerance
      in transgenic Tg2576 mice, a model of Alzheimer's disease (AD). Here we report
      that by 8 months of age, Tg2576 mice had lower basal serum insulin concentrations
      and exhibited a delayed insulin-induced reduction in blood glucose levels
      relative to wild-type mice. However, the basal levels of blood glucose and
      percent glycosylated hemoglobin (%HbA1c) were similar between the two groups of
      mice. While the basal levels of serum corticosterone were similar between Tg2576
      and wild-type mice, an overnight fasting caused a greater rise in serum
      corticosterone levels and an excessive reduction in serum insulin concentrations
      in the transgenics. At 9 months of age, we began administering Tg2576 mice
      rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma
      that increases peripheral insulin sensitivity, and after 6 weeks of
      administration the Tg2576 mice had the same response to insulin and increase in
      serum corticosterone levels after an overnight fast as did wild-type mice. By 13
      months of age, untreated Tg2576 mice had become hyperinsulinemic, in contrast to
      Tg2576 mice administered rosiglitazone for 4 months where the serum insulin
      concentrations were maintained at levels observed in wild-type mice. These
      results provide evidence for a relationship between insulin resistance, impaired
      regulation of insulin and glucose levels, and aberrant stress responses in Tg2576
      mice.

PMID- 15571986
TI  - In vitro model of neurotoxicity of Abeta 1-42 and neuroprotection by a
      pentapeptide: irreversible events during the first hour.
AB  - The cell biology of Alzheimer's disease (AD) is characterized mainly by the
      neurodegeneration caused by the beta-amyloid (Abeta) peptides and by the
      formation of neurofibrillary tangles. The initial events of neurodegeneration in
      the brain tissue include synaptic dysfunction and axonopathy. Abeta-induced
      axonopathy and neurite degeneration were studied in vitro on differentiated human
      derived neurotypic SH-SY5Y cells. Different methods were used to investigate the
      mechanism of action of aggregated Abeta on neuroblastoma cells. Abeta 1-42
      aggregated for 1 h induced irreversible changes in the neurite morphology. Change
      of tau hyperphosphorylation and cell viability (cytoplasmic redox state and
      active membrane uptake) was irreversible during the first hour after the addition
      of Abeta 1-42 to the cells. These rapid events indicate that Abeta might induce
      neurodegeneration even at an early stage of Abeta-cell contact. A novel
      pentapeptide LPYFD-amide, an analog of Soto's LPFFD, significantly decreased
      neurite degeneration, tau aggregation, and cell viability reduction induced by
      Abeta 1-42.

PMID- 15571987
TI  - Longitudinal observation on CSF Abeta42 levels in young to middle-aged amyloid
      precursor protein/presenilin-1 doubly transgenic mice.
AB  - To relate levels of beta-amyloid42 (Abeta42) in the cerebrospinal fluid (CSF) and
      brain in early Alzheimer's disease, we repeatedly measured CSF Abeta42 levels in
      transgenic mice carrying Swedish amyloid precursor protein and presenilin-1
      mutations, at ages before and after amyloid deposition. Hippocampal Abeta42
      levels were measured at the endpoints. In APPswe/PS1(A246E) mice, CSF Abeta42
      levels significantly increased between 5 and 7 months of age but did not change
      between 8 and 13 months despite a rapid increase in brain Abeta42. Furthermore, a
      decline in CSF Abeta42 levels was observed between 6 and 9 months in
      APPswe/PS1dE9 mice with faster pathology. Interestingly, the initial CSF Abeta42
      concentrations correlated more strongly with brain Abeta42 levels than the
      endpoint CSF Abeta42. Our results suggest that the levels of CSF Abeta42
      initially reflect the rate of Abeta42 production, but after reaching a critical
      concentration stay in equilibrium, until plaque formation leads to decreased CSF
      Abeta42 levels.

PMID- 15571988
TI  - Describing the HIV/AIDS epidemic: using HIV case data in addition to AIDS case
      reporting.
AB  - PURPOSE: We examined the demographic and risk characteristics of persons with HIV
      using traditional AIDS case reporting and the more recent system that includes
      HIV diagnoses without AIDS. METHODS: Using data from 25 states with HIV reporting
      of HIV/AIDS cases diagnosed from 1994 through 2001, we calculated percentage
      distributions, annual diagnosis rates, and estimated annual percent change (EAPC)
      for persons with HIV (all HIV diagnoses with or without AIDS) and persons with
      AIDS. RESULTS: The age at diagnosis of persons with all stages of HIV tended to
      be younger than that of the subset of persons with AIDS. Annual diagnosis rates
      decreased more among AIDS cases (men: EAPC, - 9.76; 95% CI, - 12.00, - 7.45;
      women: EAPC, - 3.40; 95% CI - 5.72, - 1.02) than for persons with HIV (men: EAPC,
      - 6.14; 95% CI, - 7.66, - 4.60; women: EAPC, - 2.99; 95% CI, - 4.15, - 1.82),
      except among women and black non-Hispanics, for whom the difference in the
      decreases in rates for both disease groups were small. Injection drug use was a
      more common mode of exposure for women with AIDS than for women with HIV.
      CONCLUSIONS: The epidemiology of HIV differs for certain key population groups
      from that of AIDS.

PMID- 15571989
TI  - Assessment of sexually transmitted diseases as risk factors for HIV
      seroconversion in a New Orleans sexually transmitted disease clinic, 1990-1998.
AB  - PURPOSE: This investigation examined the role of ulcerative and non-ulcerative
      sexually transmitted diseases (STDs) in increasing susceptibility to HIV
      seroconversion in a large population of uninfected and predominantly heterosexual
      persons attending a New Orleans STD clinic. METHODS: A retrospective cohort of
      clients with repeat HIV tests between January 1990 and April 1998 was constructed
      using three independent sources of information. Multivariate Cox regression was
      used to identify risk factors for HIV seroconversion while controlling for the
      effects of behavioral risk factors. A time-dependent covariate for STD allowed
      HIV seroconversion to be examined in relation to the timing of STD diagnosis.
      RESULTS: Having a recent syphilis or GUD diagnosis was associated with
      significantly increased hazards of seroconversion (among men: hazard ratio [HR],
      4.2 [2.4-7.2]; among women: 5.0 [1.9-13.0]). Among men with no history of GUD or
      syphilis, those with recent gonorrhea within 1 year prior to seroconversion were
      2.8 (1.5-5.2) times as likely to seroconvert. CONCLUSIONS: This study suggests
      that both ulcerative and non-ulcerative STD may be associated with increased risk
      of HIV transmission and therefore comprehensive STD control strategies may be
      particularly effective tools for HIV prevention.

PMID- 15571990
TI  - Leukemia risk in caprolactam workers exposed to benzene.
AB  - PURPOSE: To investigate the leukemia risk in a group of benzene exposed workers.
      METHODS: We conducted a retrospective cohort mortality study on 311 men who
      worked between January 1, 1951 and December 31, 1968 in a Caprolactam plant in
      the Netherlands. In the production of Caprolactam (the Nylon 6 monomer) pure
      benzene is used as an extracting agent and the workers at this plant have been
      exposed to substantial concentrations of benzene. The cohort was followed for
      mortality until January 1, 2001. The total mortality was below the expected
      number, which was mainly caused by a deficit of cardiovascular disease mortality.
      RESULTS: In the total group, there was one death from leukemia, compared with an
      expected number of 1.17. Despite the substantial exposures to benzene (on average
      159 ppm-years per person) there was no indication for increased leukemia
      mortality within the cohort. We have applied earlier quantitative risk
      assessments to our cohort and conclude that some of these assessments
      overestimate the risk observed in our cohort of Caprolactam workers.

PMID- 15571991
TI  - Theory and methodology for utilizing genes as biomarkers to determine potential
      biological mixtures.
AB  - PURPOSE: Genetically determined mixture information can be used as a surrogate
      for physical or behavioral characteristics in epidemiological studies examining
      research questions related to socially stigmatized behaviors and horizontally
      transmitted infections. A new measure, the probability of mixture discrimination
      (PMD), was developed to aid mixture analysis that estimates the ability to
      differentiate single from multiple genomes in biological mixtures. METHODS: Four
      autosomal short tandem repeats (STRs) were identified, genotyped and evaluated in
      African American, European American, Hispanic, and Chinese individuals to
      estimate PMD. Theoretical PMD frameworks were also developed for autosomal and
      sex-linked (X and Y) STR markers in potential male/male, male/female and
      female/female mixtures. RESULTS: Autosomal STRs genetically determine the
      presence of multiple genomes in mixture samples of unknown genders with more
      power than the apparently simpler X and Y chromosome STRs. Evaluation of four
      autosomal STR loci enables the detection of mixtures of DNA from multiple sources
      with above 99% probability in all four racial/ethnic populations. CONCLUSIONS:
      The genetic-based approach has applications in epidemiology that provide viable
      alternatives to survey-based study designs. The analysis of genes as biomarkers
      can be used as a gold standard for validating measurements from self-reported
      behaviors that tend to be sensitive or socially stigmatizing, such as those
      involving sex and drugs.

PMID- 15571992
TI  - Spouse selection and environmental effects on spouse correlation in lung function
      measures.
AB  - PURPOSE: Concordance between spouses may be due to partner selection factors
      and/or the effects of marriage/environment. The extent to which partner selection
      factors contribute to spouse concordance has important implications for
      heritability studies. The aim of this study was to examine the magnitude of
      spouse correlation in lung function measures and its relationship to duration of
      marriage. METHODS: Cross-sectional and longitudinal data collected over the
      period 1969 to 1995 for 2615 couples from the Busselton Health Study have been
      analyzed using the program FISHER. RESULTS: Unadjusted correlations were around
      0.45 for forced expiratory volume in 1 second (FEV1) and 0.25 for FEV1/FVC
      (forced vital capacity) and were reduced to 0.05 and 0.10, respectively, after
      adjustment for age, height, and smoking. No trend with marriage duration was
      apparent in both cross-sectional and longitudinal analyses but there was a
      significant downward trend in the correlations with age at marriage. CONCLUSIONS:
      The findings indicate that observed correlations in lung function measures are
      mostly due to partner selection factors and that partner selection factors have
      greater influence for couples that marry at younger ages. Family studies that aim
      to identify and separate genetic from other influences on lung function measures
      should not regard the mother-father correlation as due to common environment
      effects.

PMID- 15571993
TI  - The influence of duration of follow-up on the association between alcohol and
      cause-specific mortality in a prospective cohort study.
AB  - PURPOSE: To investigate whether duration of follow-up influences the association
      between alcohol and cause-specific mortality in a prospective cohort study with
      only baseline assessment of alcohol intake. METHODS: In a cohort of 14,223 men
      and women participating in the first investigation of the Copenhagen City Heart
      Study between 1976 and 1978 and followed until 2001, we assessed whether the
      association between alcohol and mortality was modified by duration of follow-up.
      The 24 years of follow-up were divided into four intervals, and Cox survival
      analyses were conducted separately for these four succeeding 6-year periods of
      follow-up. RESULTS: The authors found differences in the predictive values of
      alcohol and beverage-specific types of alcohol depending on duration of follow-up
      both in terms of all-cause mortality and death from coronary heart disease and
      cancer. The apparent protective effect of a moderate alcohol consumption on
      coronary heart disease attenuated during prolonged follow-up, whereas high
      alcohol consumption became associated with higher risk of death from cancer with
      longer follow-up. CONCLUSIONS: This study accentuates the importance of taking
      duration of follow-up into consideration when interpreting risk estimates from
      prospective studies on the association between alcohol and mortality.

PMID- 15571994
TI  - Age- and sex-specific income gradients in alcohol-related hospitalization rates
      in an urban area.
AB  - PURPOSE: This study examines the effects of age and sex on the relationship
      between neighborhood income and alcohol-related hospitalization rates in a large
      urban area. METHODS: Adults in Toronto, Canada, who were hospitalized with an
      alcohol-related condition between 1995 and 1998 were identified using discharge
      diagnoses. Income quintiles were determined based on area of residence. Annual
      rates of hospitalization for alcohol-related conditions per 10,000 individuals
      were calculated. RESULTS: Rates of hospitalization with a primary diagnosis of an
      alcohol-related condition were similar among men age 20 to 39 in all incomes
      quintiles, but were inversely associated with income among men age 40 to 64 (28.8
      and 13.3 per 10,000 in the lowest and highest income quintiles). Among women age
      40 to 64, the lowest income quintile had the highest hospitalization rate (12.1
      per 10,000), but women in all other income quintiles had relatively low
      hospitalization rates (5.9 to 7.7 per 10,000). As age increased above 65 years,
      rates of hospitalization with a primary diagnosis of an alcohol-related condition
      decreased or stabilized in both men and women. CONCLUSIONS: The inverse
      association between income level and alcohol-related hospitalization rates
      becomes apparent after age 40. A gradient in hospitalization rates is seen in men
      across all income levels, but in women a prominent effect is seen only in those
      with the lowest income.

PMID- 15571995
TI  - Screening for asthma by population ranking: a validation study.
AB  - PURPOSE: A neural network system was previously developed to rank a population in
      order of asthma probability based on responses to a postal questionnaire.
      Respondents ranked higher than a percentage point screening threshold are offered
      clinical review. The present study validates this system in a new population that
      had not been involved in system development. METHODS: The system was used to rank
      respondents to a community survey and to predict positive predictive value (PPV)
      for percentage point thresholds between the top 1% and 10% of the ranking.
      Respondents in the top 10% were invited for clinical review. Review information
      and expert opinion was used to designate respondents as clinically "asthmatic" or
      "non-asthmatic." PPV prediction for each threshold was compared with clinical
      status of respondents. RESULTS: As the threshold increased from 1% to 10%, the
      additional yield of clinical asthmatics decreased, indicating a ranking in asthma
      probability order (all 7 in the top 1% were clinical asthmatics compared with 91%
      of the top 5% and 83% of the top 10%). Percentages of clinical asthmatics were
      generally slightly higher than system PPV predictions. CONCLUSIONS: The system
      ranked the population in asthma probability order and estimated PPV
      conservatively, enabling health-care providers to predict resource implications
      of a screening program.

PMID- 15571996
TI  - Inconsistencies between self-reported ethnicity and ethnicity recorded in a
      health maintenance organization.
AB  - PURPOSE: Information on patient ethnicity in hospital admissions databases is
      often used in epidemiologic and health services research. However, the extent of
      consistency of these data with self-reported ethnicity is not well studied,
      particularly for specific Asian subgroups. We examined agreement between
      ethnicity in records of a sample of members of five Northern California Kaiser
      Permanente medical centers with self-reported ethnicity. METHODS: Subjects were
      3168 cases and 2413 controls aged 45 years and older from a study of fractures.
      Ethnicity recorded in the Kaiser admissions database (primarily inpatient) was
      compared with self-reported ethnicity from the study interviews. RESULTS: Among
      study subjects with available Kaiser ethnicity, sensitivities and positive
      predictive values of the Kaiser classification were high among blacks (0.95 for
      both measures) and whites (0.98 and 0.94, respectively), slightly lower among
      Asians (0.88 and 0.95, respectively), and considerably lower among Hispanics
      (0.55 and 0.81, respectively) and American Indians (0.47 and 0.50, respectively).
      Among Asian subgroups, the proportion classified as Asian was high among Chinese
      (0.94) and Japanese (0.99) but lower among Filipinos (0.79) and other Asians
      (0.74). Among the 228 (4%) subjects who self-identified with multiple
      ethnicities, 13 of 18 white + Hispanic subjects were classified as being white,
      and of the 77 subjects identifying as part American Indian, only one was
      classified as being American Indian in the Kaiser database. CONCLUSIONS: Given
      the importance of ethnicity information, medical facilities should be encouraged
      to adopt policies toward collecting high quality data.

PMID- 15571997
TI  - The relationship between body mass index and a plasma lipid peroxidation
      biomarker in an older, healthy Asian community.
AB  - PURPOSE: To examine the association between body mass index (BMI) and the plasma
      level of a lipid peroxidation biomarker in a large sample of elderly healthy
      Asian population. This cross-sectional study included 1150 community-dwelling
      Japanese aged 70 years or older in 2002. METHODS: We measured the lipid
      peroxidation biomarker 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) using the
      ELISA method. We also measured the weight and height and calculated the BMI as
      weight (kg)/height (m)2. RESULTS: After adjustment for potential confounders, the
      mean +/- SE plasma 8-iso-PGF(2alpha) level was significantly higher in subjects
      with higher BMI: 21.1 +/- 0.8 pg/ml in those with BMI of 30.0 or more; 20.5 +/-
      0.3 pg/ml in those with BMI between 25.0 and 29.9; 20.0 +/- 0.2 pg/ml in those
      with BMI between 18.5 and 24.9; and 19.0 +/- 0.7 pg/ml in those with BMI of less
      than 18.5 (p for trend = 0.011). CONCLUSIONS: Our results demonstrated that in
      the healthy Asian population, there was a modest but significant relationship
      between BMI and the plasma lipid peroxidation level.

PMID- 15571999
TI  - Pleconaril--an advance in the treatment of enteroviral infection in immuno
      compromised patients.

PMID- 15572000
TI  - Survey of acyclovir-resistant herpes simplex virus in the Netherlands: prevalence
      and characterization.
AB  - BACKGROUND: Widespread and frequent use of acyclovir (ACV) for treatment,
      suppressive therapy and prophylaxis of herpes simplex virus (HSV) infections and
      its over the counter availability may be associated with emergence of HSV
      resistance. OBJECTIVES: To determine the prevalence of ACV-resistant HSV isolates
      in different patient groups between 1999 and 2002 in the Netherlands. STUDY
      DESIGN: A total of 542 isolates, 410 HSV-1 and 132 HSV-2, from 496 patients were
      screened for reduced susceptibility to ACV. A newly developed ELVIRA HSV
      screening assay was used that allowed a high throughput screening. The genotypic
      analysis of the HSV thymidine kinase gene was performed to identify resistance
      associated mutations. RESULTS: Thirteen isolates, 8 HSV-1 and 5 HSV-2, from 10
      patients (2%) were found resistant to ACV. A single ACV-resistant strain was
      identified among isolates from 368 immunocompetent patients (0.27%; 95%
      confidence interval [CI], 0.007%-1.5%), whereas in nine isolates from 128
      immunocompromised patients resistant HSV was identified (7%; 95% CI, 3.26%
      12.93%). The highest frequency of ACV-resistant HSV was associated with bone
      marrow transplantation: four patients out of 28 (14.3%) shed resistant virus. In
      addition, resistant virus was obtained from two HIV-positive patients, one
      patient with a hematological malignancy and two patients on immunosuppressive
      drugs. Further testing showed that none of the isolates was resistant to
      foscarnet. Several new mutations were identified in the thymidine kinase gene of
      these resistant isolates, and their effect on ACV-resistance is discussed.
      CONCLUSIONS: Our study shows that the prevalence of ACV resistance is low in
      immunocompetent patients (0.27%), whereas ACV-resistant HSV infections occur
      relatively frequently in immunocompromised patients (7%; P < 0.0001). This
      emphasizes the need for drug susceptibility monitoring of HSV infections in
      immunocompromised patients with persisting infections despite antiviral therapy.

PMID- 15572002
TI  - Clinical features and molecular characterization of hepatitis A virus outbreak in
      a child care center in Thailand.
AB  - BACKGROUND: As a result of declining hepatitis A endemicity in Thailand, an
      increasing number of children and adolescents have become susceptible to
      hepatitis A virus (HAV) infection. OBJECTIVE: The present study was aimed at both
      investigating the clinical features and determining molecular characterization of
      HAV during an outbreak, which occurred in a childcare center located in a
      suburban area of Bangkok between November 2002 and February 2003. METHODS: Serum
      samples obtained from all children in the center were tested for anti-HAV IgG and
      anti-HAV IgM. Testing for HAV-RNA was performed in sera, saliva and stool samples
      by the reverse transcription-polymerase chain reaction (RT-PCR) with primers
      located at the VP1-2A region. To further characterize the HAV genotype serum
      derived HAV-RNA-positive PCR products were sequenced. RESULTS: Anti-HAV IgG and
      anti-HAV IgM were detected in 74 and 70 of 112 children in the center,
      respectively. Among those positive for anti-HAV IgM, 65 cases were asymptomatic,
      while five children had acute clinical hepatitis. The ratio between symptomatic
      and asymptomatic children was 1:13. Among the asymptomatic cases, 31 (47.7%)
      displayed biochemical hepatitis with elevated alanine aminotransferase (ALT)
      levels. All the isolates from this outbreak were found to be of subgenotype IA,
      which showed a high level of sequence homology with previous Thai isolates. HAV
      RNA could not be detected in saliva, but was found in stool for at least 3 weeks
      after initial diagnosis of clinical or biochemical hepatitis. CONCLUSION: Because
      of the infection's characteristically asymptomatic spread, hepatitis A poses an
      increased risk to childcare centers. The presence of a single sub-genotype
      indicates that this HAV strain has been predominantly circulating in Thailand.

PMID- 15572001
TI  - Physical status of HPV-16 in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Infection with high-risk human papillomavirus (HPV) has been
      implicated as one of the risk factors of esophageal squamous cell carcinoma
      (ESCC). Integration of viral DNA into host genome is essential for carcinogenesis
      since it promotes disruption of the HPV E2 gene, leading to abnormal expression
      of E6 and E7 oncoproteins. OBJECTIVES AND STUDY DESIGN: To investigate the viral
      integration status of HPV-16 infection in ESCC, 35 HPV-positive ESCC specimens
      collected from Chinese patients were subject to real-time quantitative PCR for
      determination of physical status of HPV-16 by analyzing the ratios of E2 to E6
      genes. RESULTS: Our results showed that only 8.6% (3/35) of the HPV-16 positive
      specimens harbored exclusively the episomal form (i.e. E2/E6 ratio > or = 1),
      whereas the remaining 91.4% contained either only the integrated form (5.7%, with
      E2/E6 ratio = 0) or a mixture of episomal and integrated forms of viral molecules
      (85.7%, with E2/E6 ratios > 0 but < 1). Amongst the 30 cancer specimens carrying
      mixed integrated and episomal forms, 28 had E2/integrated E6 ratios of less than
      1, indicating a predominance of integrated form of viral genes in these lesions.
      CONCLUSION: Our finding of frequent integration of viral DNA in the host genome
      suggests that integration HPV-16 is common in ESCC from Chinese patients and
      implies that HPV infection may play a role in the pathogenesis of ESCC.

PMID- 15572003
TI  - Detection of herpes simplex virus, cytomegalovirus and Epstein-Barr virus DNA in
      atherosclerotic plaques and in unaffected bypass grafts.
AB  - BACKGROUND: Herpes virus infections are suspected to be involved in the
      pathogenesis of atherosclerosis. OBJECTIVE AND METHOD: Viral DNA of herpes
      simplex virus (HSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was
      analyzed by real-time PCR on 48 biopsies from atherosclerotic plaques extracted
      by end-arterectomy (46 coronary arteries, 2 carotid arteries), and in tissue from
      non-atherosclerosis vessels from the same patient as controls (23 internal
      mammary arteries, 43 saphenous veins). RESULTS: HSV-1 DNA was detected
      significantly more frequently in plaques (35%) than in control veins (9%, P =
      0.006). However, the frequency of HSV-1 DNA detection in the internal mammary
      artery grafts was as high as in plaques (22%, P = 0.28). CMV and EBV DNA were
      exclusively found in plaques but not in controls, with 10% for CMV (P = 0.06
      versus veins, P = 0.17 versus graft arteries) and 2% for EBV (P = 1.0),
      respectively. HSV-2 was neither detected in plaques nor in controls. Herpes viral
      DNA was significantly associated only with arterial hypertension but not with
      other classical risk factors (P = 0.02), in accordance with the hypothesis that
      herpes viral infection may alter the vessel wall. CONCLUSION: We conclude that
      herpes viral infections may have a role in atherosclerosis and that the presence
      of herpes viral DNA in the grafts used for bypass surgery might constitute a
      potential risk for atherosclerosis or restenosis.

PMID- 15572004
TI  - The prevalence of HPV-18 and variants of E6 gene isolated from cervical cancer
      patients in Taiwan.
AB  - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide.
      It has been considered that human papillomavirus (HPV) is associated with
      cervical cancer. Currently, more than 80 different serotypes of HPV have been
      characterized and they are divided into low- and high-risk groups. The most
      common types that lead to cervical cancer are HPV-16 and -18. The viral oncogenes
      E6 and E7 are associated with the development of cervical cancer. In previous
      study, the variants of HPV-16 E6 gene have been reported. It suggests that
      variants may influence the morbidity of carcinogenesis, but the variant study on
      HPV-18 remains unknown. OBJECTIVES: To identify the variants of integrated HPV-18
      E6 gene in the prevalent infection of HPV-18 of cervical cancer patients. STUDY
      DESIGN: 25 cervical cancer patients were clinically identified and the biopsies
      were obtained. The infectious HPV types were identified by PCR and Southern
      blotting analysis. The DNA fragments of the integrated HPV-18 E6 were amplified
      by PCR and cloned. The nucleotide sequences were obtained by sequencing. RESULTS:
      The prevalence of HPV infection in our 25 cases was HPV-18 (100%) and 7 out of
      these 25 cases (28%) were co-infected with HPV-16. The most dominant mutation
      among 25 tested patients was a silence mutation C183G of the E6 coding region.
      CONCLUSIONS: The prevalent HPV infectious serotype is HPV-18, which differs from
      the worldwide prevalent type. The identified HPV-18 E6 variants had a unique
      silence mutation located on C183G in E6 coding region.

PMID- 15572005
TI  - Molecular epidemiology of HCV infection among acute and chronic liver disease
      patients in Kolkata, India.
AB  - BACKGROUND: In recent years, hepatitis C virus (HCV) infection is gaining
      importance in Asian countries. Recent studies conducted in different parts of the
      world revealed that there is a genotypic correlation of disease severity and
      treatment outcome. OBJECTIVES: A detailed study was carried out to delineate the
      genotypic distribution of HCV among acute and chronic liver disease patients in
      Kolkata, a city in eastern India. STUDY DESIGN: Acute and chronic liver disease
      was diagnosed among patients attending hepatitis clinics in the city. Anti-HCV
      ELISA was performed on the blood samples of the cases and positive samples were
      tested for presence of HCV-RNA and genotyping of the samples were carried out by
      reverse transcription and polymerase chain reaction (RT-PCR) and sequencing.
      RESULTS: Seroprevalence of HCV infection among acute (11.0%) and chronic (25.3%)
      hepatitis patients were high and among them 97 (75.8%) and 323 (86.1%) were HCV
      RNA positive for acute and chronic hepatitis patients, respectively. Genotyping
      by PCR showed that the predominant genotype was 3b (42.3%) followed by 3a (28.9%)
      among acute hepatitis group whereas among chronic hepatitis group, the most
      prevalent genotypes were 3a (34.7%) and 3b (47.7%). Sequence analysis of the
      untypeable isolates revealed the presence of a rare subtype 6b. CONCLUSIONS: The
      study revealed very high prevalence of HCV among acute and chronic hepatitis
      patients with predominance of genotype 3. Subtype 6b was commonly found in
      Thailand but not in India. The detection of this rare strain of Thai origin
      reveals the spread of HCV infection from Thailand to other parts of Asia. This
      observation necessitates further intensive surveillance of HCV infection in India
      to unravel the distribution of genotypes in the country and to correlate disease
      severity and treatment outcome to the genotype prevalence.

PMID- 15572006
TI  - Standardization of a neutralizing anti-vaccinia antibodies titration method: an
      essential step for titration of vaccinia immunoglobulins and smallpox vaccines
      evaluation.
AB  - The possibility of mass population vaccination with smallpox vaccine implies the
      development of anti-vaccinia immunoglobulins for the treatment of severe side
      effects following vaccination. We have chosen to develop and validate the "gold
      standard method" (plaque reduction neutralization assay) to titrate neutralizing
      anti-vaccinia antibodies in two different French laboratories belonging to the
      Department of Defense (CRSSA) and to the French Health Products Safety Agency
      (Afssaps). The results of precision, linearity and accuracy of the method led to
      consider the method as validated. In parallel, we have prepared and lyophilized a
      pool of anti-vaccinia plasma samples issued from a unique donor and qualified
      this preparation versus the first British standard to use it as an in-house
      standard with a titer of 25 international units (IU). This work will allow to
      titrate, in IU, sera from vaccinated persons in order (i) to titrate purified
      anti-vaccinia immunoglobulin preparations for vaccine severe side effect
      treatments; (ii) to investigate the level of neutralizing antibodies in the
      general population; and (iii) to investigate clinical trials of new generation
      smallpox vaccines. In the future, this will allow comparability of studies on
      either smallpox vaccines or on the serological status of the population.

PMID- 15572007
TI  - The precore mutation is associated with severity of liver damage in Brazilian
      patients with chronic hepatitis B.
AB  - BACKGROUND: The clinical relevance of the G1896A precore mutation in chronic
      hepatitis B is still poorly understood. OBJECTIVES: To assess the frequency of
      G1896A precore mutation in Brazilian patients with chronic hepatitis B, as well
      as its relation to the viral genotype, serum HBV-DNA levels and liver damage.
      STUDY DESIGN: Fifty chronic hepatitis B patients (29 HBeAg-negative and 21 HBeAg
      positive) were studied. HBV-DNA was quantified by the Amplicor HBV Monitor test
      and precore region and S gene were amplified and submitted to automatic
      sequencing. The histological activity index (HAI), degrees of hepatic fibrosis
      and distribution of core antigen (HBcAg) in hepatocytes were determined. RESULTS:
      Precore mutation occurred in 1/21 (4.8%) HBeAg-positive patients and in 17/29
      (58.6%) HBeAg-negative (p < 0.0001). Genotype D was identified in 56.5%, genotype
      A in 41.3%, and genotype F in 2.2%. The frequency of genotypes D and A, as well
      as serum levels of ALT and HBV-DNA were similar in patients infected with wild
      type and with precore mutant. Patients infected with precore mutant presented a
      higher frequency of moderate/severe HAI (p: 0.03) and moderate/severe fibrosis
      and cirrhosis (p: 0.03) than those infected with wild type. There was no
      association between G1896A mutation and cytoplasmic expression of HBcAg.
      CONCLUSIONS: Precore mutation was frequent among Brazilian subjects with chronic
      hepatitis B and its presence was associated with greater severity of liver
      disease.

PMID- 15572008
TI  - Performance of drug-resistance genotypic assays among HIV-1 infected patients
      with predominantly CRF02_AG strains of HIV-1 in Abidjan, Cote d'Ivoire.
AB  - OBJECTIVE: We evaluated the performance of three genotypic assays to detect
      resistant mutations among HIV-1 infected patients with known antiretroviral drug
      resistance profile in Abidjan, Cote d'Ivoire, most of whom had the circulating
      recombinant form (CRF02_A/G) of HIV-1. METHODS: The 56 patients analyzed in this
      study were enrolled in a pilot program to make available antiretroviral therapy
      (ART) to HIV-infected patients in Abidjan through the UNAIDS Drug Access
      Initiative (DAI). These patients had failed ART, as demonstrated by rebound in
      RNA viral load. Their plasma samples had been previously analyzed for ART
      genotypic drug-resistance by VircoGEN (Mechelen, Belgium) and were known to have
      primary and secondary resistance mutations, and also had phenotypic drug
      resistance by a recombinant virus assay technology (Mechelen, Belgium). The two
      assays we evaluated were: VircoGEN, TruGene HIV-1, and ViroSEQ HIV-1 assays.
      RESULTS: For the reverse transcriptase gene, all 27 samples that had the T215Y/F
      mutation were detected by VircoGEN , ViroSEQ, and TrueGene. All 19 (100%) samples
      that had the K70R/E mutation detected by VircoGEN were detected by ViroSEQ, and
      18 (94.7%) by TrueGene. All ten samples with the M184V mutation, three with the
      K65R, two with the G190A mutation, one with the K103N mutation, and one with the
      V75T mutation were detected similarly by all three assays. For the protease gene,
      all three assays detected the I84V (n = 1), M46I (n = 1), and L90M (n = 1)
      mutations. CONCLUSION: These results suggest that any of these assays should be
      considered for monitoring the occurrence of drug resistance among HIV-infected
      patients receiving antiretroviral therapy in West Africa.

PMID- 15572009
TI  - Detection of an acute asymptomatic HBsAg negative hepatitis B virus infection in
      a blood donor by HBV DNA testing.
AB  - The issue of HBV DNA screening on blood donations is controversially discussed
      since the economic impact of post-transfusion hepatitis B is expected to be
      relatively low. We report on a case of HBsAg negative unapparent acute HBV
      infection, which was detected by HBV NAT testing on 96-member maxi-pools with a
      commercially available NAT assay, which has a detection threshold of 3 IU/mL of
      plasma. The presence of an HBsAg escape mutant could be excluded by sequencing
      the amplified DNA. Follow-up testing showed the presence of an acute HBV
      infection (anti-HBc-IgM positive) and finally anti-HBs seroconversion. Although
      the reduction of the diagnostic window with NAT screening on maxi-pools may be
      relatively low, it may help to improve the residual risk of blood donation,
      especially in asymptomatic HBV infection, where the HBsAg positive period may be
      very short and low levels of circulating surface antigen are present. It would
      also permit to detect occult HBV infection in chronic carriers who are HBsAg
      negative. Since the viral load in chronic isolated anti-HBc positive carriers is
      low, there is a potential risk for failure of HBV DNA detection with pool-PCR in
      blood donors. Anti-HBc screening would reduce the residual risk.

PMID- 15572010
TI  - Discrepancies in viral gastroenteritis diagnosis: an unusual dual reovirus
      adenovirus infection case.
AB  - BACKGROUND: A variable rate of false-positive results may be observed with
      commercial assays for the detection of rotavirus and adenovirus antigen in stool
      specimens, depending on the quality of the reagents and the presence of
      potentially interfering substances in stool samples. OBJECTIVE: The present
      report analyse the discrepant results that could be obtained by the commercially
      available diagnostic tests and that can mask the reliable viral diagnosis. STUDY
      DESIGN: One fecal sample was collected from a hospitalized child aged 6 months
      with acute watery diarrhea and dehydration. The fecal specimen was processed the
      same day for the rotavirus and adenovirus antigen detection. RESULTS: The sample
      was positive for rotavirus antigen by one-step membrane test based on
      immunochromatographic assays (ICA) and enzyme immunoassays (EIA) monoclonal test
      but it was negative by an EIA polyclonal test, polyacrylamide gel electrophoresis
      (PAGE) and RT-PCR assays. In the other hand, the sample was positive for
      adenovirus antigen by ICA and EIA adenovirus type 40/41. Finally, the sample
      showed by PAGE an electrophoretic profile resembled that of reovirus. CONCLUSION:
      The use of a wide repertory of diagnosis tests allowed to reach an unusual
      reovirus-adenovirus type 40/41 dual infection. This case also point out the
      potential participation of reovirus in the ethiology of the diarrhea illness.

PMID- 15572011
TI  - Frequency of normal cerebrospinal fluid protein level and leukocyte count in
      enterovirus meningitis.

PMID- 15572012
TI  - Research partnerships and collaboration in cardiovascular nursing.

PMID- 15572013
TI  - Complexity in caring for an ageing heart failure population: concomitant chronic
      conditions and age related impairments.
AB  - The complexity of caring for the ageing heart failure (HF) population is further
      complicated by concomitant chronic conditions (i.e., polypharmacy, depression),
      age related impairments (i.e., hearing, visual and cognitive impairments,
      impairments in activities of daily living (ADL/IADL), and other issues (e.g.,
      health illiteracy, lack of social support). This paper provides an overview of
      these risk factors, outlines how they individually and in interplay endanger
      favourable outcome by putting patients at risk for poor self-management.
      Moreover, suggestions are made on how these issues could be addressed and
      integrated in heart failure management by applying gerontological care principles
      in caring for the ageing heart failure population.

PMID- 15572015
TI  - Why call it health-related quality of life when you mean perceived health status?
AB  - Health-related quality of life is a term frequently used in health services and
      nursing research. However, when using this term, researchers often refer to the
      self-perceived health status or the functional abilities of the patients. Since
      there is increasing evidence that quality of life and health status are distinct
      concepts, the appropriateness of the term 'health-related quality of life' is
      questionable. Therefore, researchers should consider whether health-related
      quality of life is actually measured if a health-status instrument is used. The
      scientific community should take up this conceptual discussion in order to make
      the concept of quality of life less ambiguous.

PMID- 15572014
TI  - Heart failure clinics in the Netherlands in 2003.
AB  - PURPOSE: Heart failure (HF) care in the Netherlands is going through a lot of
      changes. Nurses have increasingly important roles in providing optimal care for
      these chronically ill patients. In this study, we describe the current number of
      HF management programs and the role of the nurses in these programs. METHOD: Data
      were collected by a national survey as part of a European HF clinic survey of the
      UNITE study group of the Working Group on Cardiovascular Nursing between February
      and March 2003 to 142 hospitals in the Netherlands. RESULTS: In 60% of the
      hospital locations, there is a HF management program. Most of the programs are
      organized as HF outpatient clinics. In all HF programs, cardiologists and nurses
      are involved. Other health care providers involved are, amongst others, general
      practitioners (29%), dieticians (59%), physical therapists (47%), social workers
      (30%) and psychologists (17%). All programs offer follow-up after discharge from
      the hospitals and in most of the programs patients have increased access to a
      health care provider. Behavioural interventions (68%), psychosocial counselling
      (64%), patient education (88%) and support of the informal caregivers (59%) are
      important components. In 90% of the programs (restricted), physical examination
      is the responsibility of the HF nurse and in 65% of the programs nurses are
      involved in optimizing medical treatment. Financial support and education of HF
      nurses is still unstructured and diverse. CONCLUSION: There is a rise in the
      number of HF programs in the Netherlands. There is diversity in content and
      intensity of these programs and the role of the nurse is not clearly defined yet.
      Research and discussion on the subject of optimal effective HF care and the role
      of the HF nurse is still needed.

PMID- 15572016
TI  - Factors that affect back pain among Hong Kong Chinese patients after cardiac
      catheterization.
AB  - BACKGROUND: Cardiac catheterization (CC) is a widely used cardiac investigation
      procedure in Hong Kong. However, back pain is frequently reported following CC
      due the prolonged bed rest after the procedure. AIM: The overall aim of this
      study was to examine factors associated with back pain among Hong Kong Chinese
      patients after femoral access for CC. METHODS: A prospective study, nested within
      a randomized clinical trial (RCT), employing secondary analysis of an existing
      data set from 419 Chinese adults receiving nonemergency CC, were used. Following
      a review of literature, gender, age, history of back pain, type of dressing on
      the puncture site, length of bed rest duration, turning privilege during bed
      rest, catheter size used for CC, duration of the procedure, duration of
      hemostasis, and body weight were identified as potential factors affecting back
      pain level. Back pain was assessed at 6 h and the next morning after CC, using
      the Numeric Pain Intensity Scale (NPIS). Analysis was done using multivariate
      analysis of variance (MANOVA), after testing for normality of the distribution.
      RESULTS: Turning privilege (p = 0.001), age (p = 0.04), and body weight (p =
      0.006) were significantly related to level of back pain at 6 h and the next
      morning after CC. CONCLUSION: Results of this study may help nurses have a better
      understanding about patients' physical needs and appropriate nursing
      interventions that can be planned to enhance patient comfort following CC.

PMID- 15572017
TI  - Measurement properties of Tai Chi exercise self-efficacy among ethnic Chinese
      with coronary heart disease risk factors: a pilot study.
AB  - BACKGROUND: Improvement in aerobic capacity and reduction in blood pressure after
      Tai Chi exercise programs in persons with coronary heart disease (CHD) or with
      CHD risk factors have been reported. Self-efficacy has been shown to be a
      consistent predictor of behavioral outcomes, now being applied to Tai Chi
      exercise. AIM: To assess the utility and appropriateness of existing tools
      measuring aspects of Tai Chi exercise self-efficacy (TCSE) in a new population,
      ethnic Chinese with CHD risk factors. Specific objectives were: (1) examine
      acceptability and feasibility; (2) determine score distributions; (3) assess the
      reliability and known-groups validity; (4) translate tool into an equivalent
      Chinese version and determine if there were any differences between ethnic
      Chinese and non-Chinese. METHODS: Following a review of the literature, two
      existing tools used with Caucasians were found and modified; a 9-item exercise
      self-efficacy tool developed by Resnick and Jenkins [Resnick B, Jenkins LS,
      Testing the reliability and validity of the Self-Efficacy for Exercise scale.
      Nurs. Res. 49(3) (2000) 154-159], and a 3-item tool developed by Li et al. [Li F,
      McAuley E, Harmer P, Duncan TE, Chaumeton NR, Tai Chi enhances self-efficacy and
      exercise behavior in older adults. J. Aging Phys. Act. 9 (2001) 161-171] to
      assess gradations of the challenge to perform Tai Chi among elderly populations.
      The modified TCSE tool was translated into Chinese and back-translated. A pilot
      study was conducted to pre-test the modified 14-item TCSE tool in ethnic Chinese
      and non-Chinese. RESULTS: A total of 18 subjects (mean age = 60 years, S.D. =
      18.4) participated. Seven subjects (39%) identified themselves as ethnic Chinese.
      Ten subjects (56%) had experience performing Tai Chi, ranging from 3 months to 17
      years (mean = 5.0 years, S.D.=5.0). Half of the subjects reported having a
      history of hypertension (n = 9, 50%), while nearly one-third reported having high
      cholesterol (n = 5, 28%). No significant difference in TCSE mean scores was found
      between ethnic Chinese and non-Chinese (p > 0.05). Internal consistency estimates
      were very high (TCSE Barriers, r = 0.95; TCSE Performance, r = 0.97). A
      statistically significant difference was found in the TCSE mean scores between
      Tai Chi practitioners and non-practitioners (TCSE Barriers, t = -3.3, p = 0.01;
      TCSE Performance, t = -2.7, p = 0.03), with Tai Chi practitioners reporting
      higher self-efficacy; thus providing initial evidence of known-groups validity.
      CONCLUSIONS: Measurement of self-efficacy to overcome barriers to Tai Chi
      exercise (TCSE Barriers) and self-efficacy to perform Tai Chi (TCSE Performance)
      functioned well in this sample. The acceptability and feasibility of this tool
      was established and known-groups validity was confirmed. Further research using
      this tool among ethnic Chinese with CHD or CHD risk factors, including those with
      less than high school education or low literacy, is recommended as the next step
      in development of TCSE.

PMID- 15572018
TI  - Depressive mood after a cardiac event: gender inequality and participation in
      rehabilitation programme.
AB  - BACKGROUND: Depressive mood after a cardiac event is common with serious
      consequences for the patient. AIMS: To compare gender in depressive mood during
      the first year after a cardiac event and to evaluate the effect of participating
      in a multidimensional secondary prevention program on depressive mood. METHODS:
      166 men and 54 women, <73 years, consecutively answered a questionnaire
      concerning depressive mood at 2 weeks, 6 weeks, 5 months and 1 year after
      discharge after a cardiac event. At 2 weeks, each patient met a nurse, and was
      informed about the disease and received individual support about lifestyle
      changes. Of those invited to participate in a secondary prevention program, 127
      patients accepted, and 93 declined participation. RESULTS: At each of the four
      follow-ups, women had significantly higher depression scores than men. Depressive
      mood in both women and men was significantly reduced at 6 weeks. Thereafter, it
      increased to the 2-week level in women and to above the 2-week level in men. No
      differences were seen in patients participating or not in secondary prevention
      programs. CONCLUSION: Women had higher depressive mood scores than men and
      secondary prevention programs failed to improve depressive mood in both women and
      men.

PMID- 15572019
TI  - Attitudes and perceptions of nurses and doctors to nurse-led and nurse-initiated
      thrombolysis--an Irish perspective.
AB  - Nurse-led and nurse-initiated thrombolysis are strategies utilised within the
      United Kingdom to reduce delays for patients with acute myocardial infarction
      (AMI) requiring thrombolytic therapy. Both strategies have been found to reduce
      delays significantly. A Reduction in the delays experienced by patients can
      increase an individual's long-term survival rate. To date, there appears to be no
      documented research pertaining to nurse-led and nurse-initiated thrombolysis
      within the Irish arena. AIM: To investigate if the attitudes and perceptions of
      nurses and doctors are positive to nurse-led and nurse-initiated thrombolysis.
      METHODS: A quantitative approach employing a comparative descriptive survey
      design was utilised. A convenience sample of 75 nurses and 28 doctors was
      obtained. FINDINGS: Highlighted that nurse-led and nurse-initiated thrombolysis
      are potential roles for coronary care nurses. There was a significant difference
      of opinion between the two professional groups regarding this initiative, with
      nurses having higher levels of agreement. Nurses were more willing to undertake
      nurse-led thrombolysis (91%) as compared to nurse-initiated (74%), with years of
      experience and education appearing to influence this decision. CONCLUSION: It is
      suggested nurse-led thrombolysis is the more favourable role to Irish nurses and
      doctors.

PMID- 15572020
TI  - A 3-year follow-up of participation in peer support groups after a cardiac event.
AB  - Secondary prevention is an important component of a structured rehabilitation
      programme following a cardiac event. Comprehensive programmes have been developed
      in many European countries, the vast majority of which are hospital based. In
      Sweden, all patients with cardiac disease are also given the opportunity to
      participate in secondary prevention activities arranged by the National
      Association for Heart and Lung Patients [The Heart & Lung School (HL)]. The aim
      of this 3-year longitudinal study was to compare persons who attended the HL
      after a cardiac event and those who declined participation, with regard to health
      aspects, life situation, social network and support, clinical data,
      rehospitalisation and mortality. Totally 220 patients were included in the study.
      The patients were asked to fill in a questionnaire on four occasions, in addition
      to visiting a health care center for physical examination. After 3 years, 160
      persons were still participating, 35 of whom attended the HL. The results show
      that persons who participated in the HL exercised more regularly, smoked less and
      had a denser network as well as more social support from nonfamily members than
      the comparison groups. This study contributes to increased knowledge among
      healthcare professionals, politicians and decision makers about peer support
      groups as a support strategy after a cardiac event.

PMID- 15572021
TI  - Better knowledge improves adherence to lifestyle changes and medication in
      patients with coronary heart disease.
AB  - BACKGROUND: Many patients with coronary heart disease (CHD) are not managed
      adequately, and we often fail to reach treatment targets. AIM: To investigate if
      knowledge of risk factors for CHD, measured by a questionnaire, would show any
      relation to advice to compliance to lifestyle changes to attain treatment goals
      and adherence to drug therapy. METHOD: Men and women <71 years who had had a
      cardiac event were screened consecutively (509) from the medical records.
      Responders (392) were interviewed, examined and received a questionnaire. Three
      hundred and forty-seven patients answered the questionnaire regarding their
      general knowledge of risk factors for CHD, compliance to lifestyle changes to
      attain treatment goals and adherence to drug therapy. RESULTS: There were
      statistically significant correlations between general knowledge about risk
      factors for CHD and compliance to certain lifestyle changes: weight, physical
      activity, stress management, diet, attainment of lipid level goals and the
      likelihood of taking prescribed blood pressure-lowering drugs. General knowledge
      of risk factors had no correlation to blood glucose or blood pressure levels nor
      on smoking habits or treatment patterns for prescribed lipid- and blood glucose
      lowering drugs. CONCLUSION: Knowledge correlates to patient behaviour with
      respect to some risk factors, which should be recognised in preventive programs.

PMID- 15572022
TI  - Drosophila Nek2 protein kinase knockdown leads to centrosome maturation defects
      while overexpression causes centrosome fragmentation and cytokinesis failure.
AB  - The Nima-related kinase 2 (Nek2) has been implicated in the regulation of
      centrosome integrity and separation in several species and is a candidate for
      cell transformation. We now show that reduction of levels of the Drosophila Nek2
      by RNAi in cultured cells leads to both dispersal of centrosomal antigens and
      formation of ectopic bodies of centrosomal antigens. Overexpression of the active
      DmNek2 kinase resulted in an increase in the number of mitotic cells with
      fragmented centrosomes. The DmNek2 protein kinase is associated with punctuate
      bodies within the centrosome consistent with its presence on centrioles. In
      addition, it is present at lower levels on the midbody during cytokinesis.
      Midbody association was enhanced following overexpression, whereupon the DmNek2
      protein kinase also localised to the cell cortex becoming concentrated in the
      region of the cleavage furrow in late telophase. Many of such cells showed
      abnormalities in the organisation of anillin and actin in the cleavage furrow
      that was associated with formation of ectopic membrane protrusions between each
      daughter cell. We discuss potential roles for DmNek2 in maintaining centrosome
      integrity in mitosis, during cytokinesis, and consequently for the fidelity of
      chromosome segregation.

PMID- 15572023
TI  - Nuclear CD38 in retinoic acid-induced HL-60 cells.
AB  - The cell surface antigen, CD38, is a 45-kDa transmembrane protein which is
      predominantly expressed on hematopoietic cells during differentiation. As a
      bifunctional ectoenzyme, it catalyzes the synthesis of cyclic ADP-ribose (cADPR)
      from NAD(+) and hydrolysis of either NAD(+) or cADPR to ADP-ribose. All-trans
      retinoic acid (RA) is a potent and specific inducer of CD38 in myeloid cells. In
      this report, we demonstrate that the nuclei of RA-treated human HL-60
      myeloblastic cells reveal enzymatic activities inherent to CD38. Thus, GDP
      ribosyl cyclase and NAD(+) glycohydrolase activities in the nuclear fraction
      increased very significantly in response to incubation with RA. With Western
      blotting, we detected in the nuclear protein fraction from RA-treated cells a
      approximately 43-kDa protein band which was reactive with the CD38-specific
      monoclonal antibody OKT10. The expression of CD38 in HL-60 nuclei was also shown
      with FACScan analysis. RA treatment gave rise to an increase in in vitro ADP
      ribosylation of the approximately 43-kDa nuclear protein. Moreover, nuclei
      isolated from RA-treated HL-60 cells revealed calcium release in response to
      cADPR, whereas a similar response was not observed in control nuclei. These
      results suggest that CD38 is expressed in HL-60 cell nuclei during RA-induced
      differentiation.

PMID- 15572024
TI  - Angiostatin directly inhibits human prostate tumor cell invasion by blocking
      plasminogen binding to its cellular receptor, CD26.
AB  - Previous studies demonstrate that one of the six plasminogen type 2 glycoforms,
      plasminogen 2epsilon, enhances invasiveness of the 1-LN human prostate tumor cell
      line in an in vitro model. Binding of plasminogen 2epsilon to CD26 on the cell
      surface induces a Ca(2+) signaling cascade which stimulates the expression of
      matrix metalloproteinase-9, required by these cells to invade Matrigel. We now
      report that angiostatin, a fragment derived from plasminogen which prevents
      endothelial cell proliferation, is also a potent, direct inhibitor of 1-LN tumor
      cell invasiveness. We studied the effect of individual plasminogen 2 glycoform
      derived angiostatins and found that only angiostatin 2epsilon binds to CD26 on
      the surface of 1-LN cells at a site also recognized by plasminogen 2epsilon. As a
      result, the plasminogen 2epsilon-induced Ca(2+) signaling cascade is inhibited,
      the expression of matrix metalloproteinase-9 is suppressed, and invasion of
      Matrigel by 1-LN cells is blocked. Angiostatin 2epsilon is also the only
      angiostatin glycoform which is able to inhibit in vitro endothelial cell
      proliferation and tubule formation. These studies suggest that, in addition to
      its ability to inhibit tumor vascularization, angiostatin 2epsilon may also
      directly block tumor metastasis.

PMID- 15572025
TI  - Cross-talk between pRb/E2F and Wnt/beta-catenin pathways: E2F1 induces axin2
      leading to repression of Wnt signalling and to increased cell death.
AB  - The pRb/E2F and Wnt/beta-catenin pathways are two of the most frequently
      deregulated pathways in human cancers. In this study, we show that E2F1 up
      regulates the expression of axin2. Further, we show that axin2 can repress Wnt
      signalling leading to reduced cell growth and increased cell death. This
      represents cross-talk between major pathways involved in the formation of
      tumours. We use our data to suggest a novel mechanism for tumour suppression.

PMID- 15572026
TI  - Epstein-Barr virus-encoded EBNA-5 binds to Epstein-Barr virus-induced Fte1/S3a
      protein.
AB  - Epstein-Barr virus (EBV) transforms resting human B cells into immortalized
      immunoblasts. EBV-encoded nuclear antigens EBNA-5 (also called EBNA-LP) is one of
      the earliest viral proteins expressed in freshly infected B cells. We have
      recently shown that EBNA-5 binds p14ARF, a nucleolar protein that regulates the
      p53 pathway. Here, we report the identification of another protein with partially
      nucleolar localization, the v-fos transformation effector Fte-1 (Fte-1/S3a), as
      an EBNA-5 binding partner. In transfected cells, Fte-1/S3a and EBNA-5 proteins
      showed high levels of colocalization in extranucleolar inclusions. Fte-1/S3a has
      multiple biological functions. It enhances v-fos-mediated cellular transformation
      and is part of the small ribosomal subunit. It also interacts with the
      transcriptional factor CHOP and apoptosis regulator poly(ADP-ribose) polymerase
      (PARP). Fte-1/S3a is regularly expressed at high levels in both tumors and cancer
      cell lines. Its high expression favors the maintenance of malignant phenotype and
      undifferentiated state, whereas its down-regulation is associated with cellular
      differentiation and growth arrest. Here, we show that EBV-induced B cell
      transformation leads to the up-regulation of Fte-1/S3a. We suggest that EBNA-5
      through binding may influence the growth promoting, differentiation inhibiting,
      or apoptosis regulating functions of Fte-1/S3a.

PMID- 15572027
TI  - G1 cell cycle arrest due to the inhibition of erbB family receptor tyrosine
      kinases does not require the retinoblastoma protein.
AB  - The erbB receptor family (EGFr, erbB-2, erbB-3, and erbB-4) consists of
      transmembrane glycoproteins that transduce extracellular signals to the nucleus
      when activated. erbB family members are widely expressed in epithelial,
      mesenchymal, and neuronal cells and contribute to the proliferation,
      differentiation, migration, and survival of these cell types. The present study
      evaluates the effects of erbB family signaling on cell cycle progression and the
      role that pRB plays in regulating this process. ErbB family RTK activity was
      inhibited by PD 158780 in the breast epithelial cell line MCF10A. PD 158780 (0.5
      microM) inhibited EGF-stimulated and heregulin-stimulated autophosphorylation and
      caused a G1 cell cycle arrest within 24 h, which correlated with
      hypophosporylation of pRB. MCF10A cells lacking functional pRB retained the
      ability to arrest in G1 when treated with PD 158780. Both cell lines showed
      induction of p27(KIP1) protein when treated with PD 158780 and increased
      association of p27(KIP1) with cyclin E-CDK2. Furthermore, CDK2 kinase activity
      was dramatically inhibited with drug treatment. Changes in other pRB family
      members were noted with drug treatment, namely a decrease in p107 and an increase
      in p130. These findings show that the G1 arrest induced through inhibition of
      erbB family RTK activity does not require functional pRB.

PMID- 15572028
TI  - Overexpression of IRS2 in isolated pancreatic islets causes proliferation and
      protects human beta-cells from hyperglycemia-induced apoptosis.
AB  - Studies in vivo indicate that IRS2 plays an important role in maintaining
      functional beta-cell mass. To investigate if IRS2 autonomously affects beta
      cells, we have studied proliferation, apoptosis, and beta-cell function in
      isolated rat and human islets after overexpression of IRS2 or IRS1. We found that
      beta-cell proliferation was significantly increased in rat islets overexpressing
      IRS2 while IRS1 was less effective. Moreover, proliferation of a beta-cell line,
      INS-1, was decreased after repression of Irs2 expression using RNA
      oligonucleotides. Overexpression of IRS2 in human islets significantly decreased
      apoptosis of beta-cells, induced by 33.3 mM D-glucose. However, IRS2 did not
      protect cultured rat islets against apoptosis in the presence of 0.5 mM palmitic
      acid. Overexpression of IRS2 in isolated rat islets significantly increased basal
      and D-glucose-stimulated insulin secretion as determined in perifusion
      experiments. Therefore, IRS2 is sufficient to induce proliferation in rat islets
      and to protect human beta-cells from D-glucose-induced apoptosis. In addition,
      IRS2 can improve beta-cell function. Our results indicate that IRS2 acts
      autonomously in beta-cells in maintenance and expansion of functional beta-cell
      mass in vivo.

PMID- 15572029
TI  - GDNF-induced leukemia inhibitory factor can mediate differentiation via the
      MEK/ERK pathway in pheochromocytoma cells derived from nf1-heterozygous knockout
      mice.
AB  - Glial cell line-derived neurotrophic factor (GDNF) can induce neuron-like
      differentiation of mouse pheochromocytoma (MPC) cell lines derived from mice with
      a heterozygous knockout mutation of nf1, the murine counterpart of the human gene
      mutated in neurofibromatosis type 1 (NF1). Here, we show that GDNF-induced
      differentiation in the MPC 862L cell line is mediated by the MEK/extracellular
      signal-regulated kinase (ERK) pathway. Neurite outgrowth, increased expression of
      growth-associated protein 43, and decreased incorporation of bromodeoxyuridine
      (BrdU) were induced by treatment with GDNF, H-RasV12, or a constitutively active
      MEK2. GDNF also induces leukemia inhibitory factor (LIF) via the MEK/ERK pathway,
      and LIF itself can elicit these differentiative changes via a cell-extrinsic
      autocrine/paracrine pathway. Treatment with anti-LIF neutralizing antibody
      depleted the differentiative activity of the conditioned medium from cells
      stimulated for MEK/ERK signaling, while recombinant LIF could induce
      differentiation in MPC cells, indicating that LIF is the sole factor with
      differentiative activity. LIF could activate MEK1/2 and STAT3, but LIF-induced
      differentiation was blocked only by the MEK1/2-specific inhibitor U0126,
      indicating that the MEK/ERK pathway is necessary for LIF action in MPC cells. Our
      findings suggest that LIF may be utilized for signaling mediated by GDNF and may
      be important in the pathobiology of neuroendocrine tumors.

PMID- 15572030
TI  - Cdc25A localisation and shuttling: characterisation of sequences mediating
      nuclear export and import.
AB  - The Cdc25 phosphatases play crucial roles in cell cycle progression by removing
      inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent
      kinases. Cdc25A is an important regulator of the G1/S transition but functions
      also in the mitotic phase of the human cell cycle. In this paper, we investigate
      the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP
      Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and
      untransformed fibroblasts. Cell fusion assays and fluorescence loss in
      photobleaching (FLIP) assays reveal that the localisation is dynamic and the
      protein shuttles between the nucleus and the cytoplasm. We demonstrate that
      nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export
      sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin
      B. A nuclear localisation signal (NLS) is also characterised, mutation of which
      leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A
      phosphatase may interact with substrates and regulators both in the nucleus and
      the cytoplasm.

PMID- 15572031
TI  - VE-cadherin is a critical molecule for trophoblast-endothelial cell interaction
      in decidual spiral arteries.
AB  - Fetal cytotrophoblasts colonize the decidual spiral arteries during pregnancy and
      partially replace the endothelium by an as yet unknown mechanism. To clarify this
      issue, we cocultured trophoblast cells (TCs) and decidual endothelial cells
      (DECs) isolated from first trimester placentae and found by electron microscopic
      analysis that TCs adhered to DECs and migrated through the interendothelial
      junctions within 24 h. Since extravillous TCs were shown by FACS analysis to
      express vascular-endothelial (VE)-cadherin and platelet endothelial cell adhesion
      molecule-1 (PECAM)-1, we investigated the role of these junctional molecules in
      TC adhesion to DECs and transendothelial migration of cytotrophoblasts. Both VE
      cadherin and PECAM-1 were present at the contact sites between TCs and DECs in
      decidual sections. TC adhesion and migration were markedly inhibited by mAbs to
      VE-cadherin and marginally by mAb to PECAM-1. Increased expression of VE-cadherin
      was observed at the contact areas between TCs and DECs, whereas PECAM-1 was found
      to be redistributed from intercellular junctions. The induction of apoptosis of
      DECs by TCs, as the mechanism responsible for their replacement, was ruled out by
      the negative staining with TUNEL of DECs cocultured with TCs and the absence of
      DNA fragmentation. In conclusion, VE-cadherin is involved in transendothelial
      migration of TCs, and replacement of DECs by TCs is not the result of apoptosis.

PMID- 15572032
TI  - Mitochondrial organization and motility probed by two-photon microscopy in
      cultured mouse brainstem neurons.
AB  - Two-photon microscopy of rhodamine 123-labeled mitochondria revealed that
      mitochondria of neurons cultured from mouse respiratory center form functionally
      coupled, dynamically organized aggregates such as chains and clusters, while
      single mitochondria were rarely seen. Mitochondrial chain structures predominate
      in dendrites, while irregularly shaped mitochondrial clusters are mostly found in
      the soma. Both types of mitochondrial structures showed chaotic Brownian motions
      and the mitochondrial chains also revealed well-directed movements. The latter
      dislocations were arrested upon mitochondrial depolarization or blockade of
      mitochondrial ATP synthesis. Depolymerization of microtubules by colchicine or
      nocodazole or inhibition of protein phosphatases by calyculin A disrupted
      mitochondrial chains and the mitochondria accumulated in the soma. Forskolin and
      IBMX reversibly blocked directed movements of mitochondria, but did not affect
      their overall spatial distribution. Thus, protein phosphorylation seems to
      control both mitochondrial transport and organization. Protein phosphorylation
      downstream of enhanced cytosolic cAMP levels apparently regulates the transition
      from motile to non-motile mitochondria, while phosphorylation resulting from
      inhibition of types 1 and 2A protein phosphatases massively disturbs
      mitochondrial organization. The complex phosphorylation processes seem to control
      the close interaction of mitochondria and cytoskeleton which may guarantee that
      mitochondria are immobilized at energetic hot spots and rearranged in response to
      changes in local energy demands.

PMID- 15572033
TI  - Characterization of a nuclear compartment shared by nuclear bodies applying
      ectopic protein expression and correlative light and electron microscopy.
AB  - To investigate the accessibility of interphase nuclei for nuclear body-sized
      particles, we analyzed in cultured cells from human origin by correlative
      fluorescence and electron microscopy (EM) the bundle-formation of Xenopus
      vimentin targeted to the nucleus via a nuclear localization signal (NLS).
      Moreover, we investigated the spatial relationship of speckles, Cajal bodies, and
      crystalline particles formed by Mx1 fused to yellow fluorescent protein (YFP),
      with respect to these bundle arrays. At 37 degrees C, the nucleus-targeted,
      temperature-sensitive Xenopus vimentin was deposited in focal accumulations. Upon
      shift to 28 degrees C, polymerization was induced and filament arrays became
      visible. Within 2 h after temperature shift, arrays were found to be composed of
      filaments loosely embedded in the nucleoplasm. The filaments were restricted to
      limited areas of the nucleus between focal accumulations. Upon incubation at 28
      degrees C for several hours, NLS vimentin filaments formed bundles looping
      throughout the nuclei. Speckles and Cajal bodies frequently localized in direct
      neighborhood to vimentin bundles. Similarly, small crystalline particles formed
      by YFP-tagged Mx1 also located next to vimentin bundles. Taking into account that
      nuclear targeted vimentin locates in the interchromosomal domain (ICD), we
      conclude that nuclear body-sized particles share a common nuclear space which is
      controlled by higher order chromatin organization.

PMID- 15572034
TI  - Transforming growth factor-beta inhibits CCAAT/enhancer-binding protein
      expression and PPARgamma activity in unloaded bone marrow stromal cells.
AB  - The molecular mechanisms regulating the adipogenic differentiation of bone marrow
      stromal cells in vivo remain largely unknown. In this study, we investigated the
      regulatory effects of transforming growth factor beta-2 (TGF-beta2) on
      transcription factors involved in adipogenic differentiation induced by hind limb
      suspension in rat bone marrow stromal cells in vivo. Time course real-time
      quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of
      gene expression showed that skeletal unloading progressively increases the
      expression of CCAAT/enhancer-binding protein (C/EBP)alpha and C/EBPbeta alpha at
      5 days in bone marrow stromal cells resulting in increased peroxisome
      proliferator-activated receptor gamma (PPARgamma2) transcripts at 7 days. TGF
      beta2 administration in unloaded rats corrected the rise in C/EBPalpha and
      C/EBPbeta transcripts induced by unloading in bone marrow stromal cells. This
      resulted in inhibition of PPARgamma2 expression that was associated with
      increased Runx2 expression. Additionally, the inhibition of C/EBPalpha and
      C/EBPbeta expression by TGF-beta2 was associated with increased PPARgamma serine
      phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARgamma
      transactivating activity. The sequential inhibitory effect of TGF-beta2 on
      C/EBPalpha, C/EBPbeta, and PPARgamma2 resulted in reduced LPL expression and
      abolition of bone marrow stromal cell adipogenic differentiation, which
      contributed to prevent bone loss induced by skeletal unloading. We conclude that
      TGF-beta2 inhibits the excessive adipogenic differentiation of bone marrow
      stromal cells induced by skeletal unloading by inhibiting C/EBPalpha, C/EBPbeta,
      and PPARgamma expression and activity, which provides a sequential mechanism by
      which TGF-beta2 regulates adipogenic differentiation of bone marrow stromal cells
      in vivo.

PMID- 15572035
TI  - Expression of MAEG, a novel basement membrane protein, in mouse hair follicle
      morphogenesis.
AB  - We screened for genes specifically expressed in the mesenchymes of developing
      hair follicles using representational differential analysis; one gene identified
      was MAEG, which encodes a protein consisting of five EGF-like repeats, a linker
      segment containing a cell-adhesive Arg-Gly-Asp (RGD) motif, and a MAM domain.
      Immunohistochemistry showed that MAEG protein was localized at the basement
      membrane of embryonic skin and developing hair follicles, while MAEG expression
      diminished at the tip of the hair bud. A recombinant MAEG fragment containing the
      RGD motif was active in mediating adhesion of keratinocytes to the substratum in
      an RGD-dependent manner. One of the adhesion receptors recognizing the RGD motif
      was found to be the alpha8beta1 integrin, the expression of which was detected in
      the placode close to MAEG-positive mesenchymal cells, but later became restricted
      to the tip of the developing hair bud. Given its localized expression at the
      basement membrane in developing hair follicles and the RGD-dependent cell
      adhesive activity, MAEG may play a role as a mediator regulating epithelial
      mesenchymal interaction through binding to RGD-binding integrins including
      alpha8beta1 during hair follicle development.

PMID- 15572036
TI  - Stabilin-1 and stabilin-2 are both directed into the early endocytic pathway in
      hepatic sinusoidal endothelium via interactions with clathrin/AP-2, independent
      of ligand binding.
AB  - Liver sinusoidal endothelial cells (LSECs) mediate clearance of hyaluronan (HA)
      and scavenger receptor ligands, for example, advanced glycation end product (AGE)
      modified proteins and oxidized lipids from the circulation. We recently cloned
      stabilin-1 and -2, two members of a novel family of transmembrane proteins
      expressed in LSECs. By using primary LSECs and HEK293 cells separately expressing
      either stabilin, we have investigated their roles in the early events of
      endocytosis with respect to localization, ligand-binding properties, and
      associations with clathrin and adaptor protein (AP)-2. Both stabilins were
      present at the cell surface, although surface levels of stabilin-1 were limited.
      In addition, stabilins were present in early endosomal antigen (EEA)-1+
      organelles colocalizing with endocytosed AGE-modified bovine serum albumin (BSA).
      Treating cells with monensin further pronounced this distribution. Recombinant
      stabilin-2, but not recombinant stabilin-1, bound HA and the scavenger receptor
      ligands AGE-modified BSA, formaldehyde-treated BSA, and collagen N-terminal
      propeptides. In LSECs, both stabilins were associated with clathrin and AP-2, but
      not with each other. These interactions did not change upon addition of exogenous
      HA, suggesting that stabilins are constitutively internalized. In conclusion,
      hepatic stabilins are both present in the early endocytic pathway, associating
      with clathrin/AP-2, but whereas stabilin-2 has a clear scavenging profile,
      stabilin-1 does not recognize these ligands.

PMID- 15572037
TI  - The stability of eukaryotic initiation factor 2-associated glycoprotein, p67,
      increases during skeletal muscle differentiation and that inhibits the
      phosphorylation of extracellular signal-regulated kinases 1 and 2.
AB  - Eukaryotic initiation factor 2-associated glycoprotein, p67, protects eIF2 from
      phosphorylation by its kinases. To understand the roles of p67 during skeletal
      muscle differentiation of mouse C2C12 myoblasts, we measured the level of p67
      during myotube formation. We noticed that the level of p67 increases during
      myoblast differentiation and this increased level is controlled at the
      translational stage. The stability of p67 in the myotubes is due to its low
      turnover rate. The phosphorylation of the extracellular signal-regulated kinases
      (ERKs 1 and 2) is high in growth-factor-mediated cycling of C2C12 myoblasts and
      this phosphorylation decreases at 96 h when these myoblasts are grown in
      differentiation medium. At this time of differentiation, the level of p67 is
      higher compared to 0 h of differentiation. p67 binds to ERK2 and inhibits its
      activity in vitro. Taken together, these results suggest that the stability of
      p67 increases during myotube formation while inhibiting the phosphorylation of
      ERKs 1 and 2.

PMID- 15572038
TI  - Cis-retinol dehydrogenase: 9-cis-retinol metabolism and its effect on
      proliferation of human MCF7 breast cancer cells.
AB  - 9-Cis-retinoic acid (RA) suppresses cancer cell proliferation via binding and
      activation of nuclear receptors, retinoid X receptors (RXRs). In vivo, 9-cis-RA
      is formed through oxidation of 9-cis-retinol by cis-retinol dehydrogenase (cRDH),
      an enzyme that we characterized previously. Since 9-cis-RA is a potent inhibitor
      of breast cancer cell proliferation, we hypothesized that overexpression of cRDH
      in breast cancer cells would result in increased production of 9-cis-RA, which in
      turn would suppress cell proliferation. To investigate this hypothesis, MCF7
      human breast carcinoma cells were transduced with cRDH cDNA (LRDHSN/MCF7), and
      the growth kinetics and retinoid profiles of cells were examined following
      treatment with 9-cis-retinol. LRDHSN/MCF7 cells showed a marked reduction in cell
      numbers (60-80%) upon treatment with 9-cis-retinol compared to vehicle alone.
      Within 24 h of treatment, approximately 75% of the 9-cis-retinol was taken up and
      metabolized by LRDHSN/MCF7 cells. Despite the rapid uptake and oxidation of 9-cis
      retinol to 9-cis-retinal, 9-cis-RA was not formed in these cells. We detect at
      least one novel metabolite formed from both 9-cis-retinol and 9-cis-retinal that
      may play a role in inhibition of MCF7 cell proliferation. Our studies demonstrate
      that 9-cis-retinol in combination with cRDH inhibits breast cancer cell
      proliferation by production of retinol metabolites other than RA.

PMID- 15572039
TI  - Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface
      are associated with defective Ras signaling.
AB  - The hydrophobic (HPB) nature of most polymeric biomaterials has been a major
      obstacle in using those materials in vivo due to low compatibility with cells.
      However, there is little knowledge of the molecular detail to explain how surface
      hydrophobicity affects cell responses. In this study, we compared the
      proliferation and apoptosis of human osteoblastic MG63 cells adhered to
      hydrophilic (HPL) and hydrophobic surfaces. On the hydrophobic surface, less
      formation of focal contacts and actin stress fibers, a delay in cell cycle
      progression, and an increase in apoptosis were observed. By using fibroblast
      growth factor 1 (FGF1) as a model growth factor, we also investigated
      intracellular signaling pathways on hydrophilic and hydrophobic surfaces. The
      activation of Ras, Akt, and ERK by FGF1 was impaired in MG63 cells on the
      hydrophobic surface. The overexpression of constitutively active form of Ras and
      Akt rescued those cells from apoptosis and recovered cell cycle progression.
      Furthermore, their overexpression also restored the actin cytoskeletal
      organization on the hydrophobic surface. Finally, the proliferative,
      antiapoptotic, and cytoskeletal effects of constitutively active Ras in MG63
      cells on the hydrophobic surface were blocked by wortmannin and PD98059 that
      inhibit Akt and ERK activation, respectively. Therefore, our results suggest that
      the activation of Ras and its downstream molecules Akt and ERK to an appropriate
      level is one of crucial elements in the determination of osteoblast cell
      responses. The Ras pathway may represent a cell biological target that should be
      considered for successful surface modification of biomaterials to induce adequate
      cell responses in the bone tissue.

PMID- 15572040
TI  - Genetic modification of the heart: chaperones and the cytoskeleton.
AB  - In the past decade, genetic modification has been extensively employed to define
      (patho)physiological roles of chaperones and the cytoskeleton in the heart,
      promoting dramatic advances in this field. Both loss-of-function and gain-of
      function approaches have been used productively. alphaB-Crystallin (CryAB) is the
      most abundant small heat shock protein (HSP) in the heart. A missense mutation
      (R120G) in CryAB that is linked to human desmin-related myopathy (DRM), has
      proved in transgenic (TG) mice to be causative, likely through compromising the
      function of both CryAB and desmin filaments and inducing aberrant protein
      aggregation. For the molecular chaperones, the consensus gained is that up
      regulation of each of the HSPs in the heart is protective against insults such as
      ischemia/reperfusion (I/R) injury. CryAB modulates protein aggregation of
      abnormal desmin. With respect to the cytoskeleton, disruption of the non
      sarcomeric actin linkage at the intercalated discs via overexpressing the VASP
      EHV1 domain is sufficient to cause dilated cardiomyopathy (DCM). Up-regulation of
      microtubule-associated protein 4 (MAP4) results in microtubule densification.
      Myocyte contractile malfunction characteristic of pressure overload hypertrophy
      is recapitulated by cardiac-restricted overexpression of MAP4. In contrast,
      overexpression of desmin filaments by itself is not detrimental to the heart.
      Although loss-of-function studies have been more limited, ablation of the desmin
      gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy
      in mice. From function studies, abnormal desmin aggregation and disruption of the
      desmin networks resulting from expression of either mutant desmin or mutant CryAB
      have been shown to remodel the heart and compromise cardiac function, suggesting
      their synergistic roles in disease pathogenesis.

PMID- 15572041
TI  - p38 Inhibition attenuates the pro-inflammatory response to C-reactive protein by
      human peripheral blood mononuclear cells.
AB  - An active role for C-reactive protein (CRP) in inflammatory vascular diseases has
      been recently suggested. Monocytes play an important role in vascular pathology
      and are activated by p38 mitogen activated protein kinase (MAPK) dependent
      mechanisms in many inflammatory settings. Therefore, we investigated whether CRP
      directly promotes a pro-inflammatory phenotype in human peripheral blood
      mononuclear cells (HPBMC) via p38 MAPK signaling. CRP exposure leads to a rapid
      phosphorylation of p38 MAPK in HPBMC. CRP-induced p38 kinase activity in HPBMC
      was blocked by treatment with an inhibitor of p38 kinase, SD-282. CRP-induced the
      expression of tissue factor protein and the secretion of IL-6, IL-8, IL-1beta,
      TNFalpha and PGE(2). Co-exposure to CRP and SD-282 blocked the secretion of these
      pro-inflammatory and pro-thrombotic mediators. CRP treatment elevated IL-6, IL-8,
      IL-1beta, TNFalpha, COX-2 and TF mRNA expression. These effects of CRP also
      required p38 activity, since SD-282 blocked mRNA induction of each. Taken
      together these data suggest a mechanistic relationship between p38 MAPK signaling
      and CRP-induced pro-inflammatory and pro-thrombotic activities in HPBMC. Thus,
      p38 inhibition may represent a novel approach to attenuate inflammation and its
      consequences in cardiovascular disease.

PMID- 15572042
TI  - A "radical" idea comes of age: mitochondrial oxidant signaling in health and
      disease.

PMID- 15572043
TI  - Hypoxic pulmonary vasoconstriction: redox regulation of O2-sensitive K+ channels
      by a mitochondrial O2-sensor in resistance artery smooth muscle cells.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is a widely-conserved mechanism for
      matching ventilation and perfusion that optimizes systemic PO(2). HPV is elicited
      by moderate alveolar hypoxia through a mechanism that is intrinsic to the
      pulmonary circulation, particularly the resistance pulmonary arteries (PA), and
      is robust even in isolated perfused lungs. Although modulated by the endothelium,
      HPV persists in denuded PA rings and PA smooth muscle cells (PASMC). Beginning
      within seconds of hypoxia, HPV plateaus in minutes and persists for hours. During
      focal hypoxia (e.g. atelectasis), HPV is restricted to the vascular segments
      serving hypoxic lobes, and diverts blood to better-ventilated segments without
      causing pulmonary hypertension (PHT). However, with global hypoxia, as occurs at
      high altitude or in the fetal lung, HPV increases pulmonary vascular resistance
      (PVR) and may contribute to PHT. This review focuses on a comprehensive Redox
      Theory of HPV but considers relevant modulatory factors (endothelin), triggering
      stimuli (cyclic ADP-ribose-induced release of sarcoplasmic reticulum (SR) Ca(2+))
      and sustaining pathways (Rho kinase-modulated Ca(2+) sensitization of the
      contractile apparatus). The Redox Theory proposes that an O(2)-sensor in
      resistance PASMC (complexes I and III of the mitochondrial electron transport
      chain (ETC)) generates reactive O(2) species (ROS) in proportion to PO(2). During
      normoxia, a redox mediator, like hydrogen peroxide (H(2)O(2)), maintains voltage
      gated O(2)-sensitive K(+) channels (Kv) in an oxidized open state. Hypoxic
      withdrawal of ROS inhibits Kv channels, thereby depolarizing PASMCs, activating L
      type voltage-gated Ca(2+) channels, enhancing Ca(2+) influx and promoting
      vasoconstriction. The role of O(2)-sensitive K(+) channels is conserved in most
      specialized O(2)-sensitive tissues, including the ductus arteriosus and carotid
      body. The unique occurrence of hypoxic vasoconstriction in the pulmonary
      circulation relates to the colocalization of an O(2)-sensor and O(2)-sensitive Kv
      channels in resistance PAs. HPV has relevance to human physiology,
      pathophysiology (high altitude pulmonary edema (HAPE) and PHT) and therapy
      (single lung anesthesia).

PMID- 15572044
TI  - Thyroid hormone analogs for treatment of hypercholesterolemia and heart failure:
      past, present and future prospects.
AB  - Thyroid hormone has the unique properties of lowering cholesterol in hypothyroid
      individuals and improving cardiac performance. Beginning in the 1950s, extensive
      efforts were made to develop thyroid hormone analogs that could utilize the
      cholesterol-lowering property in euthyroid individuals without affecting the
      heart. These efforts culminated in the development of analogs that selectively
      bind to beta1-type nuclear thyroid hormone receptors (TRs), which are responsible
      for cholesterol-lowering activity, without activating alpha1-type receptors in
      the heart. beta1-Selective compounds may be useful in lowering cholesterol in
      euthyroid individuals who are intolerant to treatment with 'statins'. Screening
      of compounds for those that might be suitable for improving cardiac performance
      in heart failure led to the identification of 3,5-diiodothyropropionic acid
      (DITPA). DITPA binds to both alpha- and beta-type TRs with relatively low
      affinity. In postinfarction models of heart failure and in a pilot clinical
      study, DITPA increased cardiac performance without affecting heart rate. This
      compound also lowers cholesterol and may be a useful adjunct to standard heart
      failure therapy. Although there is both experimental and clinical evidence
      indicating that thyroid analogs act differently than thyroid hormones, the
      details of their mechanism of action have not been completely elucidated. A
      number of potential mechanisms are reviewed, including serum protein binding,
      tissue disposition, receptor binding, and gene activation. Clinical trials for
      thyroid hormone analogs are in prospect.

PMID- 15572045
TI  - Calcium channel gamma6 subunits are unique modulators of low voltage-activated
      (Cav3.1) calcium current.
AB  - The calcium channel gamma (gamma) subunit family consists of eight members whose
      functions include modulation of high voltage-activated (HVA) calcium currents in
      skeletal muscle and neurons, and regulation of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propanoic acid (AMPA) receptor targeting. Cardiac myocytes
      express at least three gamma subunits, gamma(4), gamma(6) and gamma(7), whose
      function(s) in the heart are unknown. Here we compare the effects of the
      previously uncharacterized gamma(6) subunit with that of gamma(4) and gamma(7) on
      a low voltage-activated calcium channel (Cav3.1) that is expressed in cardiac
      myocytes. Co-expression of both the long and short gamma(6) subunit isoforms,
      gamma(6L) and gamma(6S), with Cav3.1 in HEK-293 cells significantly decreases
      current density by 49% and 69%, respectively. Two other gamma subunits expressed
      in cardiac myocytes, gamma(4) and gamma(7), have no significant effect on Cav3.1
      current. Neither gamma(6L), gamma(6S), gamma(4) nor gamma(7) significantly affect
      the voltage dependency of activation or inactivation or the kinetics of Cav3.1
      current. Transient expression of gamma(6L) in an immortalized atrial cell line
      (HL-1) significantly reduces the endogenous low voltage-activated current in
      these cells by 63%. Green fluorescent protein tagged gamma(6L) is localized
      primarily in HEK-293 cell surface membranes where it is evenly distributed.
      Expression of gamma(6L) does not affect the level of Cav3.1 mRNA or the amount of
      total Cav3.1 protein in transfected HEK-293 cells. These results demonstrate that
      the gamma(6) subunit has a unique ability to inhibit Cav3.1 dependent calcium
      current that is not shared with the gamma(4) and gamma(7) isoforms and is thus a
      potential regulator of cardiac low voltage-activated calcium current.

PMID- 15572046
TI  - Genome-wide expression profiling of a cardiac pressure overload model identifies
      major metabolic and signaling pathway responses.
AB  - Cardiac hypertrophy is a predictor of cardiovascular morbidity and mortality
      independent of other risk factors. Pressure overload induces the development of
      left ventricular hypertrophy (LVH) and left atrial enlargement (LAE) in the
      mammalian heart. To systematically investigate the transcriptional changes, which
      mediate these processes, we have performed a genome-wide transcriptional
      profiling of each of the four heart chambers from mice subjected to transverse
      aortic constriction (TAC). A major new finding of this analysis is that during
      enlargement the left atrium undergoes radical changes in gene transcription that
      may play a significant role in pathophysiology. Structural changes in the LA and
      LV are correlated with significant changes in the transcriptional profile of
      these chambers, with thousands of differentially expressed known and novel
      factors. Statistical analysis of the results identified Gene Ontology biological
      process groups with significant group-wide changes, including angiogenesis,
      energy pathways, fatty acid oxidation, oxidative phosphorylation, cytoskeletal
      and matrix reorganization, and G-protein coupled receptor (GPCR) signaling. To
      facilitate future research, a searchable annotated Internet database has been
      constructed that allows access to the expression data presented here. Further
      study of these genes and processes will lead to better understanding of pathways
      involved in the pathophysiology of the cardiac response to pressure overload.

PMID- 15572047
TI  - Mechanisms underlying enhanced cardiac excitation contraction coupling observed
      in the senescent sheep myocardium.
AB  - Ageing related stiffening of the vascular system is believed to be in part
      responsible for a number of clinical outcomes including hypertension and heart
      failure. In the present study, we sought to determine whether there are
      alterations in cardiac excitation contraction coupling that may help compensate
      for the increased vessel stiffness. Experiments were performed on single cardiac
      myocytes isolated from young (18 months) and aged (>8 years) sheep. Intracellular
      Ca(2+) concentration, action potentials, L-type Ca(2+) currents and SR Ca(2+)
      content were measured at 23 degrees C. With ageing, cell capacitance increased by
      26% indicating cellular hypertrophy. Action potential duration (APD90) (590 +/-
      21 vs. 726 +/- 36 ms), Ca(2+) transient amplitude (112 +/- 15 vs. 202 +/- 25 nmol
      l(-1)) and fractional cell shortening (by 37%) also increased in the aged hearts
      (all values P < 0.05). The larger Ca(2+) transient amplitude observed under
      current clamp conditions was maintained under voltage clamp control; however, SR
      Ca(2+) content was identical. Both the peak L-type Ca(2+) current (2.8 +/- 0.3
      vs. 4.9 +/- 0.5 pA pF(-1)) and integrated Ca(2+) entry (5.1 +/- 0.7 vs. 7.9 +/-
      0.8 micromol l(-1), all P < 0.01) were greater in aged cells. In this study we
      show that in the ageing ovine myocardium, the amplitude of the systolic Ca(2+)
      transient is increased. The larger Ca(2+) transients cannot simply be explained
      by changes in APD and we suggest that the greater inward L-type Ca(2+) current
      provides a more effective trigger for calcium-induced-calcium release from the SR
      whilst maintaining a stable SR Ca(2+) content. These changes in cardiac
      excitation contraction coupling may help maintain cardiac output in the face of
      increased great vessel stiffness.

PMID- 15572048
TI  - Leukemia inhibitory factor reduces contractile function and induces alterations
      in energy metabolism in isolated cardiomyocytes.
AB  - Interleukin (IL)-6 related cytokines may be involved in the pathophysiology of
      heart failure. Leukemia inhibitory factor (LIF) is an IL-6 related cytokine, and
      elevated levels of LIF have been found in failing hearts. The aim of our study
      was to investigate how LIF may influence isolated cardiomyocytes. Adult
      cardiomyocytes were isolated from male Wistar rat hearts and treated with 1 nM
      LIF for 48 h. Contractile function was measured using a video-edge detection
      system. Fractional shortening was reduced at 0.25 Hz in LIF treated cells (7.4%
      +/- 0.5%) compared to control cells (9.0% +/- 0.7%). Gene expression analysis
      showed that expression of the mitochondrial ATP-synthase F(1) alpha subunit was
      reduced in cells exposed to LIF. The activity of the enzyme was also reduced in
      these cells (0.10 +/- 0.05 mumol/min per mg protein) compared to controls (1.23
      +/- 0.40 mumol/min per mg protein). The levels of ATP and creatine phosphate were
      reduced by 15.0% +/- 3.0% and 11.2% +/- 2.7% in LIF treated cells. LIF increased
      both (3)H-deoxyglucose uptake and lactate levels, suggesting an increase in
      anaerobic energy metabolism. Beta-oxidation of (14)C-oleic acid was increased by
      51.2% +/- 14.1% following LIF treatment, but no changes were found in cellular
      uptake or oxidation of (14)C-oleic acid to CO(2). In conclusion, LIF induces
      contractile dysfunction and changes in energy metabolism in isolated
      cardiomyocytes.

PMID- 15572049
TI  - GATA-4 regulation of myocardial survival in the preconditioned heart.
AB  - Recent studies identified that GATA-4 is a stress responsive transcription factor
      and can exert cell survival signaling in cardiac myocytes. The present study was
      designed to examine whether GATA-4 is modulated by ischemic preconditioning (PC),
      and ischemia/reperfusion (I/R). PC of isolated rat hearts was elicited by
      perfusing with Krebs-Henseleit bicarbonate buffer with four cyclic episodes of 5
      min ischemia and 10 min reperfusion. Some hearts were then subjected to 30 min
      ischemia followed by 2 h reperfusion. PC increased the DNA binding activity of
      GATA-4 compared to control, while I/R downregulated GATA-4 expression. Activation
      was associated with post-translational modifications of GATA-4 via acetylation.
      As nitric oxide (NO) may be involved in PC and I/R, we examined whether NO could
      modulate GATA-4 in HL-1 cardiac muscle cells. An NO donor, sodium nitroprusside
      (SNP), downregulated GATA activity and GATA-4 mRNA expression. We cloned the 5'
      flanking region of human GATA-4 gene and found that the luciferase activity
      controlled by this region was also suppressed by NO. A protein kinase G (PKG)
      inhibitor KT5823 inhibited SNP-induced downregulation of GATA-4, while YC-1
      (guanylyl cyclase activator) and dibutyryl cGMP (PKG activator) downregulated
      GATA-4. Thus, GATA-4 is modulated by PC, I/R and NO, and might regulate cardiac
      myocyte survival and apoptosis.

PMID- 15572050
TI  - Novel C-terminus frameshift mutation, 1122fs/147, of HERG in LQT2: additional
      amino acids generated by frameshift cause accelerated inactivation.
AB  - OBJECTIVE: The function of the C-terminus region of the human ether-a-go-go
      related gene (HERG) has not been well characterized except for its involvement in
      trafficking. To understand further the role of C-terminus region, we performed a
      functional analysis of a novel frameshift mutation (1122fs/147) identified in a
      Japanese long QT syndrome 2 (LQT2) patient who had recurrent episodes of syncope.
      METHODS: Wild type (WT) and mutant HERG plasmids were transfected into human
      embryonic kidney (HEK-293) cells, and whole-cell current was recorded by the
      patch-clamp technique. Confocal microscopy was performed to examine the membrane
      distribution of channel protein using a green fluorescent protein tagged to the N
      terminus of HERG. RESULTS: The mutant 1122fs/147 alone could express current, but
      reduced density by 74% of control. No dominant negative effect was noted with co
      expression of WT and 1122fs/147. Activation and deactivation time constants were
      not changed, while inactivation was accelerated in 1122fs/147 compared to WT, and
      V(1/2) of steady-state inactivation curve shifted by 11 mV in the negative
      direction. Current density of 1123stop mutant revealed 49% reduction compared to
      WT and showed no shift in steady-state inactivation. Confocal microscopy revealed
      reduced protein expression on the cell surface both in 1122fs/147 and 1123stop
      mutants compared to WT. CONCLUSION: Frameshift mutation at the C-terminus region
      with additional 147 amino acids evoked a loss of function of the HERG channel. A
      negative shift in steady-state inactivation induced by the additional 147 amino
      acids and trafficking defect contribute to a reduced current amplitude of
      1122fs/147.

PMID- 15572051
TI  - Opening of Ca2+-activated K+ channels is involved in ischemic preconditioning in
      canine hearts.
AB  - Brief periods of ischemia that precede sustained ischemia can markedly reduce
      infarct size (IS), a phenomenon that is known as ischemic preconditioning (IP).
      Several investigators have shown that elevation of the intracellular Ca(2+) level
      ([Ca(2+)](i)) during the antecedent brief periods of ischemia triggers the
      cardioprotective mechanism of IP. Since opening of Ca(2+) activated K(+) (K(Ca))
      channels is reported to be cardioprotective, we hypothesized that these channels
      may be involved in the cardioprotective mechanism of IP. In anesthetized open
      chest dogs, myocardial ischemia/reperfusion injury was created by occlusion of
      the left anterior descending coronary artery (LAD) for 90 min followed by 6 h of
      reperfusion. First, we showed that the treatment with NS1619, a K(Ca) channel
      opener, reduced IS (IS in NS1619 group and control group, 19.8 +/- 5.5% vs. 45.4
      +/- 3.5% of the area at risk, P < 0.05). Next, four cycles coronary occlusion for
      5 min and reperfusion (IP) were performed before the 90-min occlusion with or
      without the infusion of potent K(Ca) channel inhibitors, iberiotoxin (IbTX) and
      charybdotoxin (ChTX). IP markedly reduced IS (IS in the IP group was 8.2 +/-
      1.8%, P < 0.01 vs. control group). Infusion of either of K(Ca) channel blockers
      during IP blunted the IS-limiting effect of IP (IS in the IP + IbTX and IP + ChTX
      groups was 30.7 +/- 7.0% and 35.5 +/- 3.7%, respectively, P < 0.05, vs. IP
      group). However, the cardioprotective effect of IP was not blunted by the
      treatment with ChTX when treated only during reperfusion (14.0 +/- 4.1%). Thus,
      we conclude that the opening of K(Ca) channel is involved in early trigger phase
      of the molecular mechanism of IP.

PMID- 15572052
TI  - Selective blockade of serotonin 5-HT2A receptor increases coronary blood flow via
      augmented cardiac nitric oxide release through 5-HT1B receptor in hypoperfused
      canine hearts.
AB  - Serotonin (5-hydroxytryptamine [5-HT]), which induces vasoconstriction via 5-HT2A
      receptors in smooth muscle cells and vasodilation through activating nitric oxide
      (NO) synthase (NOS) via 5-HT1B receptors in endothelial cells, possesses
      divergent effects on regulating vascular tone. These facts lead us to consider
      that sarpogrelate, a 5-HT2A receptor blocker, may increase coronary blood flow
      (CBF) via either attenuation of vasoconstriction through 5-HT2A receptor blockade
      or augmentation of vasodilation by relative stimulation of NOS through 5-HT1B
      receptor and we tested this hypothesis in ischemic canine hearts. In open chest
      dogs, coronary perfusion pressure was reduced so that CBF was decreased to 33% of
      the baseline and kept constant. Thereafter, sarpogrelate was infused selectively
      into the left anterior descending artery with and without either an inhibitor of
      NOS (NG-nitro-L-arginine methyl ester (L-NAME)) or a 5-HT1B receptor antagonist
      (GR55562). An intracoronary administration of sarpogrelate increased CBF (34.0 +/
      4.0 to 44.5 +/- 4.4 ml/100 g/min, P < 0.05), along with the cardiac NOx release
      (3.2 +/- 0.6 to 6.8 +/- 1.2 nmol/ml, P < 0.05). The increases in both CBF and NOx
      by sarpogrelate were completely blunted by the co-administration of either L-NAME
      or GR55562. Interestingly, sarpogrelate increased the cardiac serotonin release (
      4.8 +/- 3.2 vs. 22.1 +/- 1.5 ng/ml, P < 0.05, respectively) in the hypoperfused
      heart. Immunohistochemical analysis showed that sarpogrelate induced serotonin
      production in ischemic cardiac myocytes. These results suggest that sarpogrelate
      increases CBF via augmented cardiac NO production through 5-HT1B receptor
      activation along with the blockade of 5-HT2A receptors. The increase in cardiac
      release of serotonin may increase NO production in the ischemic heart.

PMID- 15572053
TI  - Defective assembly and trafficking of mutant HERG channels with C-terminal
      truncations in long QT syndrome.
AB  - Mutations in the human ether-a-go-go-related gene (HERG) cause long QT syndrome
      type 2 (LQT2). HERG encodes a voltage-gated potassium channel consisting of four
      subunits. Tetrameric assembly is required for the formation of functional HERG
      channels. In the present work, we studied the role of assembly in HERG channel
      dysfunction of LQT2 mutations Q725X and R1014X, both of which cause truncations
      of the C-terminus of HERG channels. When expressed in HEK293 cells, Q725X did not
      generate HERG current, while R1014X generated HERG current with markedly reduced
      amplitude. Western blot analysis showed that both mutations caused defective
      trafficking of HERG channel proteins. Using sucrose gradient centrifugation we
      showed that wild type HERG and R1014X formed a tetrameric structure, whereas
      Q725X was expressed as a monomer. When coexpressed with wild type HERG, R1014X,
      but not Q725X, caused dominant negative suppression of wild type HERG current.
      Coimmunoprecipitation experiments showed that the lack of dominant negative
      effect by Q725X was due to failure of mutant subunits to coassemble with wild
      type subunits. These results suggest that the Q725X mutation causes HERG channel
      dysfunction by disruption of tetrameric assembly of HERG channels. In contrast,
      the R1014X mutation is capable of forming tetrameric structure, and it causes
      HERG channel dysfunction by defective trafficking of the mutant protein.

PMID- 15572054
TI  - Simvastatin enhances myocardial angiogenesis induced by vascular endothelial
      growth factor gene transfer.
AB  - Statins have cardioprotective roles. We explored the cardiac angiogenic effects
      of simvastatin in combination with transient overexpression of vascular
      endothelial growth factor (VEGF). Compared with normal mice, 1-year-old ApoE(-/-)
      mice fed on a high-fat diet (HFD) had about 30% less myocardial capillary (P <
      0.001) and arteriolar (P < 0.03) densities, associated with decreased VEGF (55%),
      VEGFR-1 (56%) and VEGFR-2 (78%) mRNA expressions and myocardial endothelial
      nitric oxide synthase (eNOS) production (58%). By contrast, angiopoietin-1 and
      angiopoietin-2 mRNA expressions were increased (500% P < 0.02, and 400% P < 0.01,
      respectively) in the ApoE(-/-) hearts. No change was observed in Tie-2 gene
      expression. Phosphorylation of antiapoptotic Akt was lower and proapoptotic p38
      mitogen-activated protein kinase (MAPK) was higher in the ApoE(-/-) mice compared
      with controls. Intramyocardial VEGF gene transfer increased capillary and
      arteriolar densities in the ApoE(-/-) mice, and simvastatin treatment further
      enhanced capillary density (P < 0.03) to a level similar to that of normal mice.
      Simvastatin did not change the lipid profile but blocked p38 MAPK phosphorylation
      in the ApoE(-/-) myocardium. Concurrent with these changes, there were increased
      levels of expression of mVEGF (P < 0.04) and VEGFR-2 (P < 0.03) mRNAs and
      increased production of eNOS (P < 0.05) in the ApoE(-/-) mice, while no changes
      were detected in the angiopoietin system. Thus, increased myocardial angiogenesis
      in the ApoE(-/-) mice following transient overexpression of VEGF is further
      increased by additional simvastatin treatment. These effects occurred
      concurrently with simvastatin-induced stimulation of the VEGF system, increased
      eNOS production and reduction in p38 MAPK phosphorylation.

PMID- 15572055
TI  - Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during
      reperfusion via the sarcolemmal KATP channel.
AB  - Inhibition of 20-hydroxyeicosatrienoic acid (20-HETE), by pretreatment with
      pharmacological inhibitors of cytochrome P450 (CYP) omega-hydroxylase, has been
      shown to reduce infarct size in canines when administered prior to ischemia.
      However, it is unknown whether these agents reduce infarct size when administered
      just prior to reperfusion and if the sarcolemmal and/or mitochondrial K(ATP)
      channels (sK(ATP) and mK(ATP)) contribute to cardioprotection. Therefore, we
      determined whether specific CYP inhibitors for epoxygenases and omega
      hydroxylases are cardioprotective when given either prior to ischemia or prior to
      reperfusion and furthermore, if selective inhibition of the sK(ATP) by HMR-1098
      or mK(ATP) by 5-hydroxydecanoic acid (5-HD) could abrogate this effect. Male
      Sprague-Dawley rats underwent 30 minutes of ischemia followed by 2 hours of
      reperfusion. Groups received either miconazole (MIC, non-selective CYP inhibitor,
      3 mg/kg), 17-octadecynoic acid (17-ODYA, CYP omega-hydroxylase inhibitor, 0,3 or
      3 mg/kg), N-methylsulfonyl-12, 12-dibromododec-11-enamide (DDMS, CYP omega
      hydroxylase inhibitor, 0,4 or 4 mg/kg), N-methanesulfonyl-6-(2
      propargyloxyphenyl)hexanamide (MS-PPOH, CYP epoxygenase inhibitor, 3 mg/kg), or
      vehicle either 10 minutes prior to ischemia or 5 minutes prior to reperfusion.
      Rats also received either HMR-1098 (6 mg/kg) or 5-HD (10 mg/kg) 10 minutes prior
      to reperfusion, with subsets of rats also receiving either MIC or 17-ODYA 5
      minutes prior to reperfusion. DDMS and 17-ODYA dose dependently reduced infarct
      size. Rats treated with MIC, 17-ODYA and DDMS, but not MS-PPOH, produced
      comparable reductions in infarct size when administered prior to ischemia or
      reperfusion compared to vehicle. HMR-1098, but not 5-HD, also blocked the infarct
      size reduction afforded by MIC and 17-ODYA. These data suggest a novel
      cardioprotective pathway involving CYP omega-hydroxylase inhibition and
      subsequent activation of the sK(ATP) channel during reperfusion.

PMID- 15572056
TI  - A new family of Fisher-curves estimates Fisher's alpha more accurately.
AB  - Fisher's alpha is a satisfactory scale-independent indicator of biodiversity.
      However, alpha may be underestimated in communities in which the spatial
      arrangement of individuals is strongly clustered, or in which the total number of
      species does not tend to infinity. We have extended Fisher's curve to allow for
      an accurate calibration of Fisher's alpha in such communities. In spite of its
      good performance, the use of this extended curve is complicated by its
      optimization procedure. Therefore, we have simulated the extended Fisher curve by
      modifying the smooth expolinear curve, using three ecologically meaningful
      parameters only, i.e. Fisher's alpha, a coefficient describing the effects of
      clustering and the maximum number of species. The resulting equations
      successfully describe species-individual relationships from both spatial and
      temporal observations on both plant and animal communities. This family of
      equations combines three advantages: Fisher's alpha can be quantified more
      accurately, the number of estimated parameters is flexible and can be kept to a
      minimum, while all parameters can legitimately be compared across sites.

PMID- 15572057
TI  - Spring-mass running: simple approximate solution and application to gait
      stability.
AB  - The planar spring-mass model is frequently used to describe bouncing gaits
      (running, hopping, trotting, galloping) in animal and human locomotion and
      robotics. Although this model represents a rather simple mechanical system, an
      analytical solution predicting the center of mass trajectory during stance
      remains open. We derive an approximate solution in elementary functions assuming
      a small angular sweep and a small spring compression during stance. The
      predictive power and quality of this solution is investigated for model
      parameters relevant to human locomotion. The analysis shows that (i), for spring
      compressions of up to 20% (angle of attack > or = 60 degree, angular sweep < or =
      60 degree) the approximate solution describes the stance dynamics of the center
      of mass within a 1% tolerance of spring compression and 0.6 degree tolerance of
      angular motion compared to numerical calculations, and (ii), despite its relative
      simplicity, the approximate solution accurately predicts stable locomotion well
      extending into the physiologically reasonable parameter domain. (iii)
      Furthermore, in a particular case, an explicit parametric dependency required for
      gait stability can be revealed extending an earlier, empirically found
      relationship. It is suggested that this approximation of the planar spring-mass
      dynamics may serve as an analytical tool for application in robotics and further
      research on legged locomotion.

PMID- 15572058
TI  - A model for radiation-induced bystander effects, with allowance for spatial
      position and the effects of cell turnover.
AB  - Bystander effects, whereby cells that are not directly exposed to ionizing
      radiation exhibit adverse biological effects, have been observed in a number of
      experimental systems. A novel stochastic model of the radiation-induced bystander
      effect is developed that takes account of spatial location, cell killing and
      repopulation. The ionizing radiation dose- and time-responses of this model are
      explored, and it is shown to exhibit pronounced downward curvature in the high
      dose-rate region, similar to that observed in many experimental systems, reviewed
      in the paper. It is also shown to predict the augmentation of effect after
      fractionated delivery of dose that has been observed in certain experimental
      systems. It is shown that the generally intractable solution of the full
      stochastic system can be considerably simplified by assumption of pairwise
      conditional dependence that varies exponentially over time.

PMID- 15572059
TI  - The potential significance of adaptive evolution and dimerization in chimpanzee
      intercellular cell adhesion molecules (ICAMs).
AB  - Cell adhesion molecules are involved in a diverse array of cellular processes.
      Recent data suggests that human immunodeficiency virus (HIV-1) co-opts their
      functions, in particular the properties of the intercellular cell adhesion
      molecules (ICAMs), to enhance viral infection and transmission. To investigate
      mechanisms that may underlie the non-progression that occurs in immunodeficiency
      virus-infected chimpanzees, we amplified the protein coding regions of multiple
      non-human primate ICAMs 1-5 and two ICAM ligands, leukocyte function-associated
      antigen-1 (LFA-1) and macrophage antigen 1 (Mac-1). We then employed a
      phylogenetic tree-based approach to comparative genomics, in order to screen for
      the presence of adaptive changes. Strong Darwinian positive selection in
      chimpanzee ICAMs 1, 2 and 3 was observed, most markedly in domains that are
      critical for the integrity and maintenance of ICAM-1 dimerization. As binding of
      ligands, including the attachment of virions, is influenced by the state of ICAM
      1 dimerization, chimpanzee ICAMs may have evolved to modulate their own
      dimerization. In concert with previous evidence suggesting an ancient retroviral
      pandemic as a prominent selective force in chimpanzee evolution, adaptation of
      chimpanzee ICAMs may have effected a mechanism that explains the lack of
      immunosuppression observed following HIV-1 or simian immunodeficiency virus
      (SIVcpz) infection.

PMID- 15572060
TI  - A three-layer continuous model of porous media to describe the first phase of
      skin irritation.
AB  - Mechanical skin irritation induces vasodilation on the line of scratch and in the
      neighboring zone. In order to model the effect of an irritation on the
      microcirculation, the vascular network has been described using a three-layer
      model. The first and last layer, considered as horizontal two-dimensional porous
      media, describe irrigation and drainage of the system, respectively. The
      intermediate layer, described by means of a lumped parameter method, does not
      permit horizontal fluxes. Hierarchical fluxes are directed from the first to the
      second layer and then towards the drainage layer in order to take into account
      physiological flow direction. Irritation is modeled by changing compliance of
      vessels situated at the entrance of the micro-circulation. The model permits to
      investigate the influence of change in compliance on flow and pressure behavior
      at microscopic and macroscopic level.

PMID- 15572061
TI  - A model for pathogen population structure with cross-protection depending on the
      extent of overlap in antigenic variant repertoires.
AB  - The persistence of discrete antigenic types among pathogens with multiple
      immunogenic loci can be explained by the action of immune-mediated competition.
      It has previously been shown that pathogen populations will self-organize into
      non-overlapping subsets of antigenic variants if cross-protection between
      pathogen types sharing any variants is high. Here, we examine the critical
      question of whether such strain structure will emerge if the degree of immune
      mediated competition is dependent on the number of variants shared between
      pathogen types, rather than in an all-or-nothing manner. Our analysis uncovers a
      progression from no strain structure through to discrete stable strain structure
      through intermediate partially structured states. This suggests that the number
      of loci or epitope regions required to detect linkage disequilibrium (as a
      manifestation of stable discrete strain structure) in pathogen populations
      correlates inversely with the strength of immune selection.

PMID- 15572062
TI  - Splitting the dynamics of large biochemical interaction networks.
AB  - This article is inscribed in the general motivation of understanding the dynamics
      on biochemical networks including metabolic and genetic interactions. Our
      approach is continuous modeling by differential equations. We address the problem
      of the huge size of those systems. We present a mathematical tool for reducing
      the size of the model, master-slave synchronization, and fit it to the
      biochemical context.

PMID- 15572063
TI  - Yeast glycolytic oscillations that are not controlled by a single oscillophore: a
      new definition of oscillophore strength.
AB  - Biochemical oscillations, such as glycolytic oscillations, are often believed to
      be caused by a single so-called 'oscillophore'. The main characteristics of yeast
      glycolytic oscillations, such as frequency and amplitude, are however controlled
      by several enzymes. In this paper, we develop a method to quantify to which
      extent any enzyme determines the occurrence of oscillations. Principles
      extrapolated from metabolic control analysis are applied to calculate the control
      exerted by individual enzymes on the real and imaginary parts of the eigenvalues
      of the Jacobian matrix. We propose that the control exerted by an enzyme on the
      real part of the smallest eigenvalue, in terms of absolute value, quantifies to
      which extent that enzyme contributes to the emergence of instability. Likewise
      the control exerted by an enzyme on the imaginary part of complex eigenvalues may
      serve to quantify the extent to which that enzyme contributes to the tendency of
      the system to oscillate. The method was applied both to a core model and to a
      realistic model of yeast glycolytic oscillations. Both the control over stability
      and the control over oscillatory tendency were distributed among several enzymes,
      of which glucose transport, pyruvate decarboxylase and ATP utilization were the
      most important. The distributions of control were different for stability and
      oscillatory tendency, showing that control of instability does not imply control
      of oscillatory tendency nor vice versa. The control coefficients summed up to 1,
      suggesting the existence of a new summation theorem. These results constitute
      proof that glycolytic oscillations in yeast are not caused by a single
      oscillophore and provide a new, subtle, definition for the oscillophore strength
      of an enzyme.

PMID- 15572064
TI  - Cooperation driven by mutations in multi-person Prisoner's Dilemma.
AB  - The n-person Prisoner's Dilemma is a widely used model for populations where
      individuals interact in groups. The evolutionary stability of populations has
      been analysed in the literature for the case where mutations in the population
      may be considered as isolated events. For this case, and assuming simple trigger
      strategies and many iterations per game, we analyse the rate of convergence to
      the evolutionarily stable populations. We find that for some values of the payoff
      parameters of the Prisoner's Dilemma this rate is so low that the assumption,
      that mutations in the population are infrequent on that time-scale, is
      unreasonable. Furthermore, the problem is compounded as the group size is
      increased. In order to address this issue, we derive a deterministic
      approximation of the evolutionary dynamics with explicit, stochastic mutation
      processes, valid when the population size is large. We then analyse how the
      evolutionary dynamics depends on the following factors: mutation rate, group
      size, the value of the payoff parameters, and the structure of the initial
      population. In order to carry out the simulations for groups of more than just a
      few individuals, we derive an efficient way of calculating the fitness values. We
      find that when the mutation rate per individual and generation is very low, the
      dynamics is characterized by populations which are evolutionarily stable. As the
      mutation rate is increased, other fixed points with a higher degree of
      cooperation become stable. For some values of the payoff parameters, the system
      is characterized by (apparently) stable limit cycles dominated by cooperative
      behaviour. The parameter regions corresponding to high degree of cooperation grow
      in size with the mutation rate, and in number with the group size. For some
      parameter values, we find more than one stable fixed point, corresponding to
      different structures of the initial population.

PMID- 15572065
TI  - An integrated model of Plasmodium falciparum dynamics.
AB  - The within-host and between-host dynamics of malaria are linked in myriad ways,
      but most obviously by gametocytes, the parasite blood forms transmissible from
      human to mosquito. Gametocyte dynamics depend on those of non-transmissible blood
      forms, which stimulate immune responses, impeding transmission as well as within
      host parasite densities. These dynamics can, in turn, influence antigenic
      diversity and recombination between genetically distinct parasites. Here, we
      embed a differential-equation model of parasite-immune system interactions within
      each of the individual humans represented in a discrete-event model of Plasmodium
      falciparum transmission, and examine the effects of human population turnover,
      parasite antigenic diversity, recombination, and gametocyte production on the
      dynamics of malaria. Our results indicate that the local persistence of P.
      falciparum increases with turnover in the human population and antigenic
      diversity in the parasite, particularly in combination, and that antigenic
      diversity arising from meiotic recombination in the parasite has complex
      differential effects on the persistence of founder and progeny genotypes. We also
      find that reductions in the duration of individual human infectivity to
      mosquitoes, even if universal, produce population-level effects only if near
      absolute, and that, in competition, the persistence and prevalence of parasite
      genotypes with gametocyte production concordant with data exceed those of
      genotypes with higher gametocyte production. This new, integrated approach
      provides a framework for investigating relationships between pathogen dynamics
      within an individual host and pathogen dynamics within interacting host and
      vector populations.

PMID- 15572066
TI  - Inference of signaling and gene regulatory networks by steady-state perturbation
      experiments: structure and accuracy.
AB  - One of the fundamental problems of cell biology is the understanding of complex
      regulatory networks. Such networks are ubiquitous in cells and knowledge of their
      properties is essential for the understanding of cellular behavior. In earlier
      work (Kholodenko et al. (PNAS 99: 12841), it was shown how the structure of
      biological networks can be quantified from experimental measurements of steady
      state concentrations of key intermediates as a result of perturbations using a
      simple algorithm called "unravelling". Here, we study the effect of experimental
      uncertainty on the accuracy of the inferred structure (i.e. whether interactions
      are excitatory or inhibitory) of the networks determined using the unravelling
      algorithm. We show that the accuracy of the network structure depends not only on
      the noise level but on the strength of the interactions within the network. In
      particular, both very small and very large values of the connection strengths
      lead to large uncertainty in the inferred network. We describe a powerful
      geometric tool for the intuitive understanding of the effect of experimental
      error on the qualitative accuracy of the inferred network. In addition, we show
      that the use of additional data beyond that needed to minimally constrain the
      network not only improves the accuracy of the inferred network, but also may
      allow the detection of situations in which the initial assumptions of unravelling
      with respect to the network and the perturbations have been violated. Our ideas
      are illustrated using the mitogen-activated protein kinase (MAPK) signaling
      network as an example.

PMID- 15572067
TI  - The evolutionary origin of signa in female Lepidoptera: natural and sexual
      selection hypotheses.
AB  - Signa are structures of the inner wall of the female corpus bursae (structure
      where males deposit a spermatophore during copulation) of many Lepidoptera that
      assist in tearing open spermatophores. In this paper, three hypotheses on the
      evolutionary origin of signa are proposed. The first hypothesis considers natural
      selection pressures arising from ecological changes that favor an increase in
      oviposition rate as the force behind the evolution of signa. The other two
      hypotheses involve sexual selection. The second hypothesis proposes that sexually
      antagonistic coevolution is responsible of the evolution of signa: According to
      this hypothesis, the inverse relation between the length of the female's
      refractory period and the amount of ejaculate remaining in her corpus bursae,
      observed in most Lepidoptera studied, selects in males a decreased rate of
      spermatophore digestion (e.g. a thicker spermatophore envelope or a higher chitin
      content) that increases the length of the refractory period beyond the female's
      optimum; in response, females evolved signa as a counteradaptation to restore the
      female's optimum by increasing the rate of spermatophore digestion. The last
      hypothesis considers that signa may have evolved as a female device for cryptic
      choice of males based on the ability of these to influence the length of post
      copulatory female refractory period. The different hypotheses make different
      predictions of the sequence of appearance of specific ecological factors and
      novel phenotypic traits through evolutionary time. Therefore, testing the
      relative importance of the hypotheses requires a formal comparative analysis.

PMID- 15572068
TI  - IMGT unique numbering for immunoglobulin and T cell receptor constant domains and
      Ig superfamily C-like domains.
AB  - IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr)
      provides a common access to expertly annotated data on the genome, proteome,
      genetics and structure of immunoglobulins (IG), T cell receptors (TR), major
      histocompatibility complex (MHC), and related proteins of the immune system (RPI)
      of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has
      allowed to define a unique numbering for the variable domains (V-DOMAINs) and for
      the V-LIKE-DOMAINs. In this paper, this standardized characterization is extended
      to the constant domains (C-DOMAINs), and to the C-LIKE-DOMAINs, leading, for the
      first time, to their standardized description of mutations, allelic
      polymorphisms, two-dimensional (2D) representations and tridimensional (3D)
      structures. The IMGT unique numbering is, therefore, highly valuable for the
      comparative, structural or evolutionary studies of the immunoglobulin superfamily
      (IgSF) domains, V-DOMAINs and C-DOMAINs of IG and TR in vertebrates, and V-LIKE
      DOMAINs and C-LIKE-DOMAINs of proteins other than IG and TR, in any species.

PMID- 15572069
TI  - Conversely to its sibling Drosophila melanogaster, D. simulans overcomes the
      immunosuppressive effects of the parasitoid Asobara citri.
AB  - The endoparasitoid Asobara citri avoids Drosophila melanogaster immune defenses,
      thanks to immune suppressive effects. We investigated whether this parasitoid
      could also circumvent the immune reaction of D. simulans, a sibling species of D.
      melanogaster. The rates of infestation, successful parasitism, total
      encapsulation and mortality were measured after complete development of both D.
      melanogaster and D. simulans larvae parasitized by A. citri. Results showed that
      the parasitoids were almost never encapsulated in D. melanogaster larvae, while
      45% were encapsulated in D. simulans. A. citri induced a targeted disruption of
      the hematopoietic organs and a decrease of the hemocytes load in host larvae of
      both species. Despite such disruptive immune effects most D. simulans larvae
      succeeded in encapsulating A. citri eggs, probably thanks to their ability to
      immediately mount a capsule after infestation. This work brings some insight into
      the diversity of the immune potentials evolved by Drosophila species towards
      parasitoids.

PMID- 15572070
TI  - Using models of nucleotide evolution to build phylogenetic trees.
AB  - Molecular phylogenetics and its applications are popular and useful tools for
      making comparative investigations in genetics; however, estimating phylogenetic
      trees is not always straightforward. Some phylogenetic estimators use an explicit
      model of nucleotide evolution to estimate evolutionary parameters such as branch
      lengths and tree topology. There are many models to choose from, and use of the
      optimal model for a particular data set is important to avoid a loss of power and
      accuracy in phylogenetic estimations. Here, we review some molecular evolutionary
      forces and the parameters included in some common models of evolution used to
      interpret resulting patterns of molecular variation. We present some statistical
      methods of selecting a particular model of nucleotide evolution, and provide an
      empirical example of model selection. Statistical model selection strikes a
      balance between the bias introduced by some models and the increased variance of
      parameter estimates that results from using other models.

PMID- 15572071
TI  - Isolation and characterization of CXC receptor genes in a range of elasmobranchs.
AB  - The CXC group of chemokines exert their cellular effects via the CXCR group of G
      protein coupled receptors. Six CXCR genes have been identified in humans (CXCR1
      6), and homologues to some of these have been isolated from a range of vertebrate
      species. Here we isolate and characterize CXCR genes from a range of elasmobranch
      species. One CXCR1/2 gene fragment isolated from Scyliorhinus caniculus (lesser
      spotted catshark), and two CXCR1/2 copies from each of the elasmobranchs,
      Cetorhinus maximus (basking shark), Carcharodon carcharias (great white shark),
      and Raja naevus (cuckoo ray), exhibit high similarity to both CXCR1 and CXCR2.
      The two copies evident in the cuckoo ray and lamniform sharks provide strong
      evidence of CXCR1/2 lineage specific duplication in rays and sharks. A CXCR
      fragment isolated from Lamna ditropis (salmon shark) shows high similarity to a
      range of CXCR4 genes and strong clustering with CXCR4 gene homologues was
      apparent during phylogenetic reconstruction.

PMID- 15572073
TI  - CpG-oligodeoxynucleotide-stimulated chicken heterophil degranulation is serum
      cofactor and cell surface receptor dependent.
AB  - Synthetic oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) is
      immune stimulatory to chicken heterophils. Recognition of CpG-ODN by chicken
      heterophils leads to the mobilization and release of granules. This CpG-ODN
      induced heterophil degranulation was chicken serum (CS)-dependent. Heat
      denaturation and membrane filtration of CS revealed that the active serum
      cofactor(s) was likely a protein in nature with a molecule mass within 50,000 to
      100,000. This serum cofactor(s) was heat-resistant at 56 degrees C for 1h. The
      involvement of a cell surface receptor in recognition of CpG-ODN was also
      demonstrated by (1) trypsin treatment of the heterophils abrogated the
      degranulation response and (2) CpG-ODN-induced heterophil degranulation was
      sensitive to the inhibition of Clathrin-dependent endocytosis. In addition, among
      various microbial agonists, including CpG-ODN, lipopolysaccharide, lipoteichoic
      acid, phorbol myristate acetate, and formalin-killed Salmonella enteritidis, CpG
      ODN was the only agonist that displayed serum-dependent induction of
      degranulation in chicken heterophils. This is the first report that shows serum
      dependent activation of leukocytes by CpG-ODN.

PMID- 15572072
TI  - Demonstration of the mucosal lectins in the epithelial cells of internal and
      external body surface tissues in pufferfish (Fugu rubripes).
AB  - We have previously identified two novel mannose-specific lectins, skin- and
      intestine-type pufflectins, in the pufferfish, Fugu rubripes [J. Biol. Chem. 278
      (2003) 20882]. In the present study, the localization of the lectins and their
      producing cells were analyzed with antibody and anti-sense probe that recognize
      both types of pufflectin. Using immunohistochemistry, pufflectins were detected
      exclusively in epithelial cells in the skin, gills, oral cavity wall and
      esophagus, whereas in both mucous and epithelial cells in the intestine.
      Messenger RNAs for pufflectins were detected only in epithelial cells of these
      tissues with in situ hybridization, suggesting that epithelial cells are able to
      produce the lectins. Pufflectins are produced and distributed in cells that cover
      the external and internal body surfaces, which might mean that Fugu have a common
      immunological system on both surfaces.

PMID- 15572074
TI  - The effects of dietary vitamin E and selenium deficiencies on plasma thyroid and
      thymic hormone concentrations in the chicken.
AB  - Beginning at hatching, male Cornell K strain single comb white leghorn chickens
      were fed a basal diet, with or without vitamin E (100 IU/kg) and/or selenium (Se,
      0.2 ppm). After 3 weeks of treatment, animals fed either the Se-deficient or
      basal diet had significantly reduced plasma Se-dependent glutathione peroxidase
      activities when compared to those fed a vitamin E and Se-supplemented diet.
      Similarly, animals fed the vitamin E-deficient or basal diet had significantly
      reduced plasma alpha-tocopherol levels. The effect of these treatments on plasma
      concentrations of thyroid hormones (T(3)/T(4)), growth hormone (GH), and thymic
      hormone (thymulin) was determined using radioimmunoassay and ELISA. A deficiency
      in Se, but not in vitamin E, resulted in an increase in plasma T(4)
      concentrations while plasma T(3) concentrations were decreased. Plasma GH levels
      showed some fluctuation as a result of the dietary treatments but there was no
      significant correlation between plasma GH levels and any of the other variables.
      A significant decrease in plasma thymulin levels was observed in Se-deficient
      birds compared to those receiving adequate Se in the diet. A vitamin E deficiency
      had no measurable effect on plasma thymulin levels. From these studies, we
      conclude that plasma thymulin concentrations directly correlate with plasma T(3)
      concentrations which are negatively affected by a Se deficiency.

PMID- 15572075
TI  - A hemolysis-hemagglutination assay for characterizing constitutive innate humoral
      immunity in wild and domestic birds.
AB  - Methods to assess immunocompetence requiring only a single sample are useful in
      comparative studies where practical considerations prevent holding or recapturing
      individuals. The assay for natural antibody-mediated complement activation and
      red blood cell agglutination described here, requiring approximately 100 microl
      of blood, is highly repeatable. The effects of complement deactivation, 2
      mercaptoethanol (2-ME), age, and lipopolysaccharide (LPS)-induced sickness
      response were examined to validate comparisons among diverse avian species.
      Complement deactivation by heating significantly reduces lysis and treatment with
      2-ME reduces both lysis and agglutination. Lysis and agglutination both increase
      with age in chickens; LPS treatment does not influence these variables in 11-week
      old chickens. In a comparison of 11 species, both lysis (0.0-5.3 titers) and
      agglutination (1.8-8.0 titers) vary significantly among species. Accordingly,
      this assay can be used to compare constitutive innate humoral immunity among
      species and with respect to age, sex, and experimental treatments within
      populations.

PMID- 15572076
TI  - Mapping hazard from urban non-point pollution: a screening model to support
      sustainable urban drainage planning.
AB  - Non-point sources of pollution are difficult to identify and control, and are one
      of the main reasons that urban rivers fail to reach the water quality objectives
      set for them. Whilst sustainable drainage systems (SuDS) are available to help
      combat this diffuse pollution, they are mostly installed in areas of new urban
      development. However, SuDS must also be installed in existing built areas if
      diffuse loadings are to be reduced. Advice on where best to locate SuDS within
      existing built areas is limited, hence a semi-distributed stochastic GIS-model
      was developed to map small-area basin-wide loadings of 18 key stormwater
      pollutants. Load maps are combined with information on surface water quality
      objectives to permit mapping of diffuse pollution hazard to beneficial uses of
      receiving waters. The model thus aids SuDS planning and strategic management of
      urban diffuse pollution. The identification of diffuse emission 'hot spots'
      within a water quality objectives framework is consistent with the 'combined'
      (risk assessment) approach to pollution control advocated by the EU Water
      Framework Directive.

PMID- 15572077
TI  - Is moral hazard good for the environment? Revenue insurance and chemical input
      use.
AB  - Using farm level data we evaluate the input use and environmental effects of
      revenue insurance. A priori, the moral hazard effect on input use is
      indeterminate. This paper empirically assesses the input use impact of the
      increasingly popular, and federally subsidized, risk management instrument of
      revenue insurance and the extent to which its effects on input use may differ
      from those of the older yield based instruments. We conclude that among winter
      wheat farmers, those who purchase revenue insurance tend to spend less on
      fertilizers but do not appreciably alter pesticide expenditures. Thus, any
      improved environmental outcomes due to crop insurance are likely due to reduced
      fertilizer not pesticide use. When the environmental indicators included
      indicated a potential environmental fragility (i.e. high erosion, pesticide
      leaching or pesticide runoff potential), the input use equation suggested that
      fertilizer expenditures decreased. Revenue insurance undoubtedly further reduces
      fertilizer applications on these fields as well, but the marginal environmental
      benefit of revenue insurance is lessened because the reduction, where it matters
      most, accrues on land on which fertilizer use has already been curtailed to some
      degree.

PMID- 15572078
TI  - An analysis of the breakdown of paper products (toilet paper, tissues and
      tampons) in natural environments, Tasmania, Australia.
AB  - An examination of the relative breakdown rates of unused toilet paper, facial
      tissues and tampons was undertaken in nine different environments typical of
      Tasmanian natural areas. Bags of the paper products (toilet paper, facial
      tissues, tampons) were buried for periods of 6, 12 and 24 months at depths of 5
      and 15 cm. A nutrient solution simulating human body wastes was added to half of
      the samples, to test the hypothesis that the addition of nutrients would enhance
      the breakdown of paper products buried in the soil. Mean annual rainfall was the
      most important measured variable determining mean breakdown in the nutrient
      addition treatment between sites, with high rainfall sites (mean annual rainfall
      of greater than 650 mm) recording less decayed products than the drier sites
      (mean annual rainfall of 500-650 mm). Temperature and soil organic content were
      important influences on the breakdown of the unfertilised products. Toilet paper
      and tissues decayed more readily than tampons. Nutrient addition enhanced decay
      for all products across all sites. Depth of burial was not important in
      determining the degree to which products decayed. In alpine environments, burial
      under rocks at the surface did not increase the speed of decay of any product.
      The Western Alpine site, typical of alpine sites in the Tasmanian Wilderness
      World Heritage Area, showed very little decay over the two-year period, even for
      nutrient enhanced products. Management prescriptions should be amended to
      dissuade people from depositing human toilet waste in the extreme (montane to
      alpine) environments in western Tasmania. Tampons should continue to be carried
      out as currently prescribed.

PMID- 15572079
TI  - Understanding the role of land use in urban stormwater quality management.
AB  - Urbanisation significantly impacts water environments with increased runoff and
      the degradation of water quality. The management of quantity impacts are straight
      forward, but quality impacts are far more complex. Current approaches to
      safeguard water quality are largely ineffective and guided by entrenched
      misconceptions with a primary focus on 'end-of-pipe' solutions. The outcomes of a
      research study presented in the paper, which investigated relationships between
      water quality and six different land uses offer practical guidance in the
      planning of future urban developments. In terms of safeguarding water quality,
      high-density residential development which results in a relatively smaller
      footprint would be the preferred option. The research study outcomes bring into
      question a number of fundamental concepts and misconceptions routinely accepted
      in stormwater quality management. The research findings confirmed the need to
      move beyond customary structural measures and identified the key role that urban
      planning can play in safeguarding urban water environments.

PMID- 15572080
TI  - Factors influencing the sustained participation of farmers in participatory
      forestry: a case study in central Sal forests in Bangladesh.
AB  - Wide acceptance of sustainable development as a concept and as the goal of forest
      management has shifted forest management policies from a traditional to a people
      oriented approach. Consequently, with its multiple new objectives, forest
      management has become more complex and an information gap exits between what is
      known and what is utilized, which hinders the sustained participation of farmers.
      This gap arose mainly due to an interrupted flow of information. With
      participatory forestry, the information flow requires a broad approach that goes
      beyond the forest ecosystem and includes the different stakeholders. Thus in
      participatory forest management strategies, policymakers, planners and project
      designers need to incorporate all relevant information within the context of the
      dynamic interaction between stakeholders and the forest environment. They should
      understand the impact of factors such as management policies, economics and
      conflicts on the sustained participation of farmers. This study aimed to use
      primary cross-sectional data to identify the factors that might influence the
      sustained participation of farmers in participatory forestry. Using stratified
      random sampling, 581 participants were selected to take part in this study, and
      data were collected through a structured questionnaire by interviewing the
      selected participants. To identify the dominant factors necessary for the
      sustained participation of farmers, logistic regression analyses were performed.
      The following results were observed: (a) sustained participation is positively
      and significantly correlated with (i) satisfaction of the participants with the
      tree species planted on their plots; (ii) confidence of the participants that
      their aspired benefits will be received; (iii) provision of training on different
      aspects of participatory forestry; (iv) contribution of participants' money to
      Tree Farming Funds. (b) The sustained participation of farmers is negatively and
      significantly correlated with the disruption of local peoples' interests through
      implementation of participatory forestry programs, and long delays in the
      harvesting of trees after completion of the contractual agreement period.

PMID- 15572081
TI  - Anticipated socio-environmental impacts of the proposed Little Darby National
      Wildlife Refuge in Ohio.
AB  - Data were collected during the summer of 2000 from 146 residents living in a
      rural area located in central Ohio that had been identified as a possible site
      for a national wildlife refuge. The purpose of the study was to assess
      anticipated socio-economic and environmental impacts of the proposed refuge on
      local people and natural ecosystems. A 'vested interests' theoretical model was
      developed to guide the investigation. The theoretical model posits that attitudes
      of local people toward externally induced projects are a function of costs and
      benefits individuals expect to receive as a result of the development action. The
      theory posits that individuals who expect to receive greater benefits from the
      refuge will exhibit more favorable attitudes toward the proposed project.
      Anticipated impacts of the proposed refuge were assessed with a Likert-type
      attitude scale that was shown to be highly reliable. Variables measuring specific
      costs and benefits associated with the proposed project were used as predictive
      variables. Descriptive statistics demonstrated that respondents believed the
      proposed wildlife refuge would generate more costs than benefits for local
      residents. Multiple linear regression findings demonstrated that six variables
      were significant in explaining 65.1% of the variance in the attitudes toward the
      proposed project. The significant variables were as follows: perceived costs and
      benefits associated with the proposed project, perceived water quality within the
      Little Darby Creek at the time of the data collection, age of primary income
      earner, expected future water quality within the Little Darby Creek, expected
      impact of farmland transition on the household, and attitude toward private
      property rights. Study findings consistently support research hypotheses.

PMID- 15572082
TI  - Inhibitory effects of butyrate on biological hydrogen production with mixed
      anaerobic cultures.
AB  - In this study batch experiments were conducted to investigate the inhibitory
      effects of butyrate addition on hydrogen production from glucose by using
      anaerobic mixed cultures. Experimental results showed that addition of butyrate
      at 4.18 and 6.27 g/l only slightly inhibited hydrogen production, and addition of
      butyrate at 8.36-12.54 g/l imposed a moderate inhibitory effect on hydrogen
      production. At addition of 25.08 g/l, butyrate had a strong inhibitory influence
      on substrate degradation and hydrogen production. The distribution of the
      volatile fatty acids produced from the acidogeneisis of glucose was significantly
      influenced by the addition of butyrate. The inhibition of butyrate addition on
      hydrogen production was described well by a non-competitive and non-linear
      inhibition model, with the maximum hydrogen production rate of 59.3 ml/g-SS/h,
      critical added butyrate concentration of 25.08 g/l, and inhibition degree of
      0.323, respectively. The C(I,50) values (the butyrate concentration at which
      bioactivity is reduced by 50%) for hydrogen production rate and yield were
      estimated as 19.39 and 20.78 g/l of added butyrate, respectively.

PMID- 15572083
TI  - Evaluating canalside hedgerows to determine future interventions.
AB  - This paper describes a project undertaken during 2001/2002 which developed a
      method for valuing hedgerows adjacent to the inland waterway network of Great
      Britain. The method enables the landowner, British Waterways, to manage their
      valuable environmental asset to achieve a good level of biodiversity and robust
      habitat balanced against the heavy amenity use the 3000 km canal network endures.
      Valuation techniques were developed using a combination of new and existing
      ecological indices for components of biodiversity, hedgerow structure and
      amenity, and synthesised into an index in an innovative combined approach. The
      resultant index was then applied to a sample 20 km section of hedge alongside the
      Grand Union Canal in Southeast England. The results obtained reflect the
      hedgerows' present value, and highlight factors that might improve or limit their
      future increase in value. The results from the case study application also
      demonstrate that there is a positive relationship between hedgerow structure and
      biodiversity, and that hedgerows in urban areas are less biodiverse and
      structurally sound than those in rural areas. Furthermore, there is a zone within
      rural areas influenced by the adjacent urban areas and/or higher amenity use. The
      paper concludes with an assessment of the approaches' strengths and weaknesses
      with a view to its compatibility with other hedgerow evaluations, such as HEGS,
      its use by other agencies or landowners, and to aid hedgerow management and
      future development.

PMID- 15572084
TI  - Cross-taxonomic potential and spatial transferability of an umbrella species
      index.
AB  - Validation that conservation of certain species effectively protects a high
      proportion of co-occurring species is rare. Our previous work has suggested that
      an umbrella index based on geographic distribution and life history
      characteristics would maximize the proportion of conspecifics protected per unit
      area conserved. Using bird and butterfly data from three mountain ranges in the
      Great Basin, we examined whether umbrella species also would confer protection to
      species in different taxonomic groups. Further, we addressed the spatial
      transferability of umbrella species by considering whether species identified as
      umbrellas in one mountain range would be effective umbrellas in other mountain
      ranges. Overall, equal proportions of species would be protected using either
      cross-taxonomic umbrella species or same-taxon umbrella species. Our data
      suggested that in a given mountain range, umbrella species identified using data
      from the same mountain range versus a different mountain range would be equally
      effective. The ability of one set of umbrella species to confer protection to co
      occurring species, however, may vary among taxonomic groups and geographic
      regions.

PMID- 15572085
TI  - Sulfur, chromium, and selenium accumulated in Chinese cabbage under direct
      covers.
AB  - Currently, pollution of our agricultural soils and waters is increasing and is
      often associated with many human health ailments. Soils contaminated with low
      levels of heavy metals and other trace elements are frequently used for growing
      vegetable crops and in such a situation, these toxic contaminants often
      accumulate in the edible portions of these agricultural plants and thereby enter
      the human food chain. In 3 consecutive years of field experiments (1994-1996),
      two different crop-covering treatments--T (50 microm perforated polyethylene),
      and T2 (17 gm(-2) non-woven polypropylene)--were used to modify the environmental
      conditions for the growth of Chinese cabbage 'Nagaoka 50' [Brassica rapa L.
      (Pekinensis group)]. Open-air plots (T(0)) were used as controls. Analytical
      determinations of chromium (Cr), selenium (Se), two forms of sulfur (total-S and
      sulfate-S), and amino acids (Isoleucine, leucine, lysine, methionine, serine,
      threonine, and valine) were performed utilizing plant shoots for analysis. The T1
      and T2 treated plants contained concentrations of lysine, methionine, serine, and
      threonine higher than in T(0). Under T1, the extent of Cr and Se removal in the
      field was more favorable. Direct covers could be used in contaminated
      agricultural zones for a variety of plant species, not just for use with those
      plants previously reported to be efficient at bio-accumulating toxic elements
      because the thermal effect created by the covers favors phytoextraction
      processes. However, it is clear that the accumulation of these toxic substances
      in the plants (Cr) would deem the plant material unsuitable for human consumption
      and use as animal fodder.

PMID- 15572086
TI  - The immunology of colorectal cancer.
AB  - Despite the fact that the vast majority of differentiated colorectal cancers
      express tumour-associated antigens (TAA's) such as Carcinoembryonic antigen (CEA)
      and Ep-CAM, the immune response particularly in advanced disease is often
      attenuated. This may result from clonal immunocyte energy to oncofetal antigens
      normally expressed during cell development, immune complex disease where the TAA
      is repeatedly shed into the circulation and tumour-induced impairments in T cell
      receptor recognition and stimulation. Commonly used monoclonal anti-TAA antibody
      therapy is also hampered by human anti-xenogeneic antibody production and by the
      physical distribution of the antibody into the center of tumour deposits where
      blood flow is limited and where tumour neovasculature is hyperpermeable.
      Moreover, animal models of colorectal cancer should be assessed carefully since
      CEA is not normally expressed, requiring the transduction of CEA cDNA into tumour
      xenografts or the creation of transgenic species where the mechanisms of tumour
      rejection are still governed by non-human antigenic histoincompatibility. All of
      this has resulted in the generation of novel immune constructs designed to
      enhance the inherent immunogenicity of colorectal cancer, using antigenic viral
      genomes or cytokine transduction methodology as well as the ex vivo stimulation
      of dendritic antigen-presenting cells or autologous tumour-infiltrating
      lymphocytes. Even these powerful strategies may be foiled by intratumoural
      mechanisms which result in excessive apoptosis of infused cells even when they
      have been shown in vitro to be immunocompetent and tumour-specific. This review
      discusses these immune approaches in colorectal cancer and their inherent
      limitations.

PMID- 15572087
TI  - Management and imaging of low rectal carcinoma.
AB  - Large variations in recurrence rates have been reported with the best results
      following total mesorectal excision (TME) surgery for low and middle rectal
      cancers. However, the low rectal cancers still have higher rates of local
      recurrence (up to 30%) whether operated by low anterior resection or
      abdominoperineal excision (APE) due to high rates of circumferential margin
      involvement. The treatment of choice for low rectal cancers that encroach upon
      the potential circumferential resection margin is surgery combined with
      preoperative neoadjuvant treatment. Preoperative chemotherapy combined with long
      term radiotherapy reduces recurrence rates and preoperative loco-regional staging
      can help to select the patients more likely to benefit from neo-adjuvant therapy.
      Surface coil MRI is the most promising modality for patient selection, which can
      provide good views of the circumferential resection margin especially the
      presence or absence of tumour encroaching the intersphincteric plane.

PMID- 15572088
TI  - Adjuvant treatment of colorectal cancer.
AB  - Colorectal cancer is one of the most frequent causes of cancer deaths. Survival
      for locoregional colorectal cancer is about 70% overall and 30-60% in stage III
      patients. Several randomized trials have shown that adjuvant chemotherapy can
      increase this survival rate. 5-Fluorouracil-based chemotherapy is strongly
      recommended in this context. There are still some questions about the setting in
      which patients should be treated as well as the optimal treatment. New data for
      different schedules and combinations are now available. Physicians have to choose
      between the different options now available to offer the best treatment to their
      patients. This Review analyses the current options for adjuvant therapy in colon
      and rectal cancer.

PMID- 15572089
TI  - Role of new agents in the treatment of colorectal cancer.
AB  - 5-Fluorouracil has been the basis of chemotherapy for colorectal cancer over the
      past 40 years. Various methods of administration of this drug have been
      investigated to identify the most efficacious form of administration. Two other
      agents in common usage are Irinotecan and Oxaliplatin. Both of these are being
      studied to determine their role as primary or second line agents and their
      efficacy in combination with each other and 5-FU. New agents undergoing
      development include COX2 inhibitors and epidermal growth factor receptor
      inhibitor targeting drugs i.e. Cetuximab, Tyrosine kinase inhibitors and Vascular
      endothelial growth factor receptor inhibitors. This article reviews the above
      mentioned drugs and includes a recommended approach to chemotherapy in metastatic
      colorectal cancer.

PMID- 15572090
TI  - Evaluating operative risk in colorectal cancer surgery: ASA and POSSUM-based
      predictive models.
AB  - OBJECTIVE: To review two predictive models, based on the American Society of
      Anaesthesiologists (ASA) and the Physiological and Operative Severity Score for
      the enumeration of Mortality and morbidity (POSSUM)-used for estimating
      postoperative mortality in patients, undergoing surgery for colorectal disease,
      in the UK. METHODS: Data was derived from three multicentre, UK-based studies
      involving a total of 16,006 patients with malignant or non-malignant bowel
      pathologies. Data sources were: The Colorectal-POSSUM (CR-POSSUM) Study
      population, comprising 6883 patients undergoing colorectal surgery in 15 UK
      hospitals between 1993 and 2001; The Association of Coloproctology of Great
      Britain and Ireland (ACPGBI) Colorectal Cancer (CRC) Database, encompassing 8077
      newly diagnosed CRC patients, undergoing surgical resections in 79 hospitals,
      between April 2000 and March 2002; The ACPGBI Malignant Bowel Obstruction (MBO)
      Study, encompassing 1046 patients with MBO in 148 hospitals, treated between
      April 1998 and March 1999. Multifactorial logistic regression analyses were used
      to adjust for case-mix, identify risk factors for in-hospital/30-day operative
      mortality and to accommodate the variability of outcomes between hospitals.
      RESULTS: In the ACPGBI CRC study, 7374 patients had surgery, 6622(89.8%) a major
      bowel resection and 1465(19.9%) emergency surgery. Nine hundred and eighty-nine
      (94.6%) patients with MBO had surgery and 854(86.3%) underwent bowel resection.
      In the CR-POSSUM study, of the 6790(98.6%) patients undergoing surgery,
      3451(50.8%) had a major colorectal resection, including 2107(31.0%) as an
      emergency. The operative mortality was 7.5% for the ACPGBI CRC study, 15.7% for
      patients with MBO and 5.7% for patients in the CR-POSSUM study. When tested, the
      predictive models showed good discrimination, with an area under the receiver
      operator characteristic curve of 77.5% for the ACPGBI CRC, 80.1% for the MBO and
      89.8% for the CR-POSSUM. CONCLUSIONS: Prediction of postoperative death can be
      made by the clinician using simple, numerical, tables derived from the ACPGBI
      CRC, MBO and CR-POSSUM models. The models can be used in everyday practice for
      pre-operative counselling of patients and their carers, as a part of the process
      of informed consent. They may also be used to compare the outcomes between
      multidisciplinary CRC teams.

PMID- 15572091
TI  - Radiotherapy and concurrent radiochemotherapy for rectal cancer.
AB  - Adjuvant radiotherapy with or without chemotherapy has been used widely in an
      attempt to improve outcome in rectal cancer. For locally advanced disease,
      postoperative radiochemotherapy significantly improved both local control and
      overall survival when compared with surgery alone or surgery plus irradiation.
      This prompted a National Cancer Institute Consensus Conference in the United
      States in 1990 to recommend postoperative radiochemotherapy for patients with TNM
      stage II and III rectal cancer as standard treatment. In Europe, several
      randomized studies tested preoperative radiotherapy in comparison to surgery
      alone and showed lower local failure rates. A recent meta-analysis concluded that
      the combination of preoperative radiotherapy and surgery, as compared with
      surgery alone, significantly improves local control and overall survival. These
      results are, however, challenged by more recent reports of extraordinarily low
      local failure rates following improved surgical techniques, including total
      mesorectal excision. Evidently, the current monolithic approaches to either apply
      the same schedule of postoperative radiochemotherapy to all patients with stage
      II/III rectal cancer or to give preoperative intensive short-course radiation
      according to the Swedish concept for all patients with resectable rectal cancer
      irrespective of tumor stage and treatment goal (e.g. sphincter preservation),
      need to be questioned.

PMID- 15572092
TI  - Sphincter-saving surgery for low rectal cancer. The experience of the National
      Cancer Institute, Milano.
AB  - The treatment of tumors of the distal rectum continues to be a matter of great
      controversy among oncologic surgeons. There are increasingly promising
      indications that functionally conservative surgery may be a valid therapeutic
      alternative to conventional therapy in patients with tumours of the lower rectum,
      traditionally treated by abdomino-perineal resection and definitive colostomy.
      Many points are presently under evaluation and we want to discuss some of the
      most relevant topics that are now permitting to change the guide lines of therapy
      of this disease. Our view of the problem is based on a personal experience
      cumulated in fourteen years of activity in a specialized unit and this paper
      reports the main results of a complex and diversified study carried out during
      this period at the National Cancer Institute of Milan.

PMID- 15572093
TI  - Laparoscopic surgery for colorectal cancer: the state of the art.
AB  - Laparoscopic techniques have expanded since their introduction 15 years ago. The
      laparoscopic approach for colorectal surgery has been slower to develop than
      other fields of surgery. However, this approach does provide significant benefits
      for colorectal resection, although concerns regarding the ability to satisfy
      oncological criteria have restricted its use in the past. This review studies the
      published data on the use of laparoscopic surgery for colorectal cancer including
      the short- and long-term outcomes. New long-term outcome data is now available
      which is likely to encourage the use of this technique for colon cancer
      resection. Laparoscopic rectal cancer resection is also discussed including the
      more limited outcome data that is available.

PMID- 15572094
TI  - Follow-up of colorectal cancer patients after resection with curative intent-the
      GILDA trial.
AB  - PURPOSE: Surgery remains the primary treatment of colorectal cancer. Data are
      lacking to delineate the optimal surveillance strategy following resection. A
      large-scale multi-center European study is underway to address this issue (Gruppo
      Italiano di Lavoro per la Diagnosi Anticipata-GILDA). METHODS: Following primary
      surgery with curative intent, stratification, and randomization at GILDA
      headquarters, colon cancer patients are then assigned to a more intensive or less
      intensive surveillance regimen. Rectal cancer patients undergoing curative
      resection are similarly randomized, with their follow-up regimens placing more
      emphasis on detection of local recurrence. Target recruitment for the study will
      be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05
      and a hazard-rate reduction of >24%). RESULTS: Since the trial opened in 1998,
      985 patients have been randomized from 41 centers as of February 2004. There were
      496 patients randomized to the less intensive regimens, and 489 randomized to the
      more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses
      (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up
      arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two
      less intensive arms as of February 2004. CONCLUSIONS: This trial should provide
      the first evidence based on an adequately powered randomized trial to determine
      the optimal follow-up strategy for colorectal cancer patients. This trial is open
      to US centers, and recruitment continues.

PMID- 15572095
TI  - Surgical strategies for colorectal liver metastases.
AB  - Colorectal cancer remains the second commonest cause of death from cancer in
      Western society. Nearly half of all patients will develop liver metastases and
      many will die with disease confined to the liver. The accepted modern definitions
      of resectability now mean that over twenty per cent of patients are now
      resectable (with operative mortality of >2%) with curative intent, and nearly one
      third will be alive, disease free, five years later. The use of additional
      techniques such as radiofrequency ablation may bring many more patients the
      possibility of long term survival. The introduction of new chemotherapy regimens,
      including those based on oxaliplatin may convert one third of non-resectable
      patients to resectability with curative intent. Therefore, in 2004 nearly one
      third of patients with disease confined to the liver can now look forward to
      possibly curative liver surgery.

PMID- 15572096
TI  - Treatment of locally advanced rectal cancer.
AB  - Historically, locally advanced rectal cancer is known for its dismal prognosis.
      The treatment of locally advanced rectal cancer is subject to continuous change
      due to development of new and better diagnostic tools, radiotherapeutic
      techniques, chemotherapeutic agents and understanding of the subject. It is
      clear, that a multimodality approach is the only way to achieve satisfactory
      local recurrence and survival rates in this type of cancer. However, which
      multimodality strategy is to be used still remains a point of controversy. This
      review summarises recent developments in imaging, (neo-) adjuvant therapy and
      surgical techniques in the treatment of primary locally advanced rectal cancer.

PMID- 15572097
TI  - Colorectal cancer presenting as surgical emergencies.
AB  - Colorectal Cancer (CRC) is a major cause of cancer morbidity and mortality.
      Surgery is considered the first line therapy for CRC, and is generally
      encountered by many surgeons under elective conditions. Unfortunately, colorectal
      cancer may present acutely as a surgical emergency. These conditions include, but
      are not limited to perforation, hemorrhage, and obstruction. The presentation of
      a patient with these conditions can lead to higher morbidity and mortality. The
      choice of operation depends mainly on the site of the disease (left-sided versus
      right-sided), the patient's physical condition, nutritional status, and age. The
      treatment for right-sided lesions is a right hemicolectomy. However, treatment of
      left-sided lesions is still undecided. There are many therapeutic options such as
      primary or staged resections, Hartman's procedure, subtotal colectomy, or
      colostomy. Other therapies involve non-operative techniques such as laser
      therapy, colonic stenting, emergency endoscopy, and comfort measures.

PMID- 15572098
TI  - Comparison between in vitro potency tests for Cuban hepatitis B vaccine:
      contribution to the standardization process.
AB  - Quality control of recombinant Hepatitis B vaccines performed by National Control
      Laboratories prior to marketing vaccine batches requires in vivo and or a well
      validated in vitro potency assays as recommended by WHO technical series. The in
      vitro test must also demonstrate its suitability for monitoring the consistency
      of the vaccine manufacturer. The aim of this study was to establish the
      relationship between both in vitro potency tests performed by Cuban manufacturer
      and National Control Laboratory for Hepatitis B vaccine and the suitability of
      our method for monitoring the manufacturer's test results and consistency. We
      also intended to contribute to the standardisation process consisting of in vitro
      methods for this vaccine.

PMID- 15572099
TI  - Comparison of the mouse antibody production (MAP) assay and polymerase chain
      reaction (PCR) assays for the detection of viral contaminants.
AB  - Mouse antibody production (MAP) tests have become the standard assay for the
      detection of murine viral contamination in biologic materials, such as cell lines
      and transplantable tumors. However, newly developed PCR assays offer the
      advantage of lower cost, faster turn around times, and eliminate the use of live
      animals. In this study, the MAP test and a panel of PCR assays were compared for
      the detection of 11 different viral contaminants of cell lines and transplantable
      tumors. The PCR assays had either better or comparable results to the MAP test
      for all agents tested. The results of this study confirm that PCR assays are an
      effective method for detection of viral contamination and can be used as an
      alternative to the MAP test.

PMID- 15572100
TI  - Development of a PCR method for mycoplasma testing of Chinese hamster ovary cell
      cultures used in the manufacture of recombinant therapeutic proteins.
AB  - Chinese hamster ovary (CHO) cell cultures used to produce biopharmaceuticals are
      tested for mycoplasma contamination as part of the ensurance of a safe and pure
      product. The current U.S. Food and Drug Administration (FDA) regulatory guideline
      recommends using two procedures: broth/agar cultures and DNA staining of
      indicator cell cultures. Although these culture methods are relatively sensitive
      to most species, theoretically capable of detecting as few as 1-10 cfu/ml of most
      species, the overall procedure is lengthy (28 d), costly and less sensitive to
      noncultivable species. The detection of mycoplasma using the polymerase chain
      reaction (PCR) method has been considered an alternative method because it is
      relatively fast (1-2 d), inexpensive, and independent of culture conditions,
      however, limitations in sensitivity (limit of detection >/=1000 cfu/ml) and the
      risk of false positive and false negative results have prevented PCR from
      replacing the traditional culture methods in the industrial setting. In this
      report, we describe a new PCR assay for mycoplasma detection that appears to
      resolve these issues while being sufficiently simple and inexpensive for routine
      use. This assay applies readily available techniques in DNA extraction together
      with a modified single-step PCR using a previously characterized primer pair that
      is homologous to a broad spectrum of mycoplasma species known to infect mammalian
      cell cultures. Analysis is made easy by the detection of only a single
      amplification product within a narrow size range, 438-470 bp. A high sensitivity
      and specificity for mycoplasma detection in CHO cell production cultures is made
      possible through the combination of three key techniques: 8-methoxypsoralen and
      UV light treatment to decontaminate PCR reagents of DNA; hot-start Taq DNA
      polymerase to reduce nonspecific priming events; and touchdown- (TD-) PCR to
      increase sensitivity while also reducing nonspecific priming events. In extracts
      of mycoplasma DNA, the limit of detection for eight different mycoplasma species
      is 10 genomic copies. In CHO cell production cultures containing gentamicin, the
      limit of detection for a model organism, gentamicin-resistant M. hyorhinis, is 1
      cfu/ml. The sensitivity and specificity of this PCR assay for mycoplasma
      detection in CHO cell production cultures appear similar to the currently used
      culture methods and thus should be considered as an alternative method by the
      biopharmaceutical industry.

PMID- 15572101
TI  - Collaborative study to assess the suitability of a candidate International
      Standard for yellow fever vaccine.
AB  - Yellow fever vaccines are routinely assayed by plaque assay. However, the results
      of these assays are then converted into mouse LD(50) using
      correlations/conversion factors which, in many cases, were established many years
      ago. The minimum required potency in WHO Recommendations is 10(3) LD(50)/dose.
      Thirteen participants from 8 countries participated in a collaborative study
      whose aim was to assess the suitability of two candidate preparations to serve as
      an International Standard for yellow fever vaccine. In addition, the study
      investigated the relationship between the mouse LD(50) test and plaque forming
      units with a view to updating the WHO recommendations. Plaque assays were more
      reproducible than mouse assays, as expected. Differences in sensitivities of
      plaque assays were observed between laboratories but these differences appear to
      be consistent within a laboratory for all samples and the expression of potency
      relative to the candidate standard vaccine improved the reproducibility of assays
      between laboratories. However, the use of potencies had little effect on the
      between laboratory variability in mouse LD(50) assays. There appears to be a
      consistent relationship between overall mean LD(50) and plaques titre for all
      study preparations other than sample E. The slope of the correlation curve is >1
      and it would appear that 10(3) LD(50) is approximately equivalent to 10(4) plaque
      forming units (PFU), based on the overall means of all laboratory results. The
      First International Standard for yellow fever vaccine, NIBSC Code 99/616, has
      been established as the First International Standard for yellow fever vaccine by
      the Expert Committee of Biological Standards of the World Health Organisation.
      The International Standard has been arbitrarily assigned a potency of 10(4.5)
      International Units (IU) per ampoule. Manufacturers and National Control
      Laboratories are including the First International Standard for yellow fever
      vaccine in routine assays so that the minimum potency in IU of vaccines released
      for use and which meet the current minimum potency of 10(3) LD(50) in mouse
      assays, can be determined. These data will be analysed before a review of the WHO
      requirements, including the minimum potency per dose, is undertaken.

PMID- 15572102
TI  - Report of a collaborative study to calibrate the Second International Standard
      for parvovirus B19 antibody.
AB  - A collaborative study was undertaken to assess the suitability of a replacement
      for the First International Standard for parvovirus B19 IgG, human serum and to
      calibrate it in IU. The proposed standard, which is a pool of sera from 16 US
      blood donors, was assayed along with the First International Standard, a coded
      duplicate of the proposed standard and a plasma sample from a single blood donor.
      Nine laboratories from eight countries participated in the studies and five
      different assay kits were used. Two kits contained VP1+VP2, one kit contained VP1
      only and two kits, one of which was used by five participants contained VP2 only.
      Differences in detection of the proposed standard and the individual plasma were
      observed with assay kits containing different antigens, VP1, VP2 or VP1+VP2.
      However, since VP1 is a minor capsid protein and on its own does not assemble
      into virus like particles and the dominant response in individuals appears to be
      against VP2, it was considered reasonable to utilize only the data from kits
      containing VP2 antigen for the calibration of the proposed standard. The results
      of this study demonstrated that the proposed standard coded 01/602 was suitable
      to serve as the replacement International Standard for parvovirus B19, serum IgG,
      and this preparation was established as the Second International Standard for
      parvovirus B19 antibody, plasma human, with an assigned unitage of 77 IU per
      ampoule by the Expert Committee on Biological Standardisation of the World Health
      Organisation in February 2003.

PMID- 15572103
TI  - Expression vectors for chicken-human chimeric antibodies.
AB  - The chicken is a useful animal for preparation of antibodies that are reactive
      with highly conserved mammalian molecules. For further clinical application of
      chicken antibodies, we constructed the novel expression vectors for chicken-human
      chimeric antibodies, pcSLCgamma1, pcSLCgamma4 and pcSLCkappa. These vectors had
      the following characteristics: (1) any chicken variable regions from hybridomas
      or a phage display library can be easily introduced; (2) the variable regions are
      able to be expressed in different immunoglobulin isotypes; and (3) the chimeric
      antibodies can be highly expressed in either transiently or stably transfected
      eukaryotic cells (COS-7 and CHO-K1 cells). Western blot analysis of the chimeric
      antibodies revealed that the expressed products were of the predicted size,
      structure and specificity. These results indicate that these vectors are useful
      tools for the chimerization of chicken antibodies.

PMID- 15572104
TI  - Selective reduction of weak synaptic activity awakens dormant synapses.
AB  - Slutsky et al. (this issue of Neuron) report that by selectively filtering out
      low-level uncorrelated synaptic activity at NMDA receptors in hippocampal
      cultures they can unlock a large reserve of quiescent synapses and make them
      available for potentiation with theta burst stimulation. These findings differ
      from previously reported activity-dependent mechanisms in that inactivity does
      not necessarily increase synaptic activity globally.

PMID- 15572105
TI  - Neural processing at the speed of smell.
AB  - Olfaction is typically described as behaviorally slow, suggesting neural
      processes on the order of hundreds of milliseconds to seconds as candidate
      mechanisms in the creation of olfactory percepts. Whereas a recent study
      challenged this view in suggesting that a single sniff was sufficient for optimal
      olfactory discrimination, a study by Abraham et al. in this issue of Neuron sets
      out to negate the challenge by demonstrating increased processing time for
      discrimination of similar versus dissimilar stimuli. Here we reconcile both
      studies, which in our view together support the notion of a speed-accuracy
      tradeoff in olfactory discriminations that are made within about 200 ms. These
      findings are discussed in light of the challenges related to defining olfactory
      perceptual similarity in nonhuman animals.

PMID- 15572106
TI  - No about face on houses in the fusiform face area!
AB  - Yovel and Kanwisher (this issue of Neuron) altered upright and inverted face and
      house characteristics during a same-different task. The right fusiform face area
      (FFA) was more active to faces than houses but, unlike behavior, was unaffected
      by spatial configuration or parts manipulations. These data raise interesting
      questions regarding the relationship of brain activation to observed behavior.

PMID- 15572107
TI  - Shrinkage of dendritic spines associated with long-term depression of hippocampal
      synapses.
AB  - Activity-induced modification of neuronal connections is essential for the
      development of the nervous system and may also underlie learning and memory
      functions of mature brain. Previous studies have shown an increase in dendritic
      spine density and/or enlargement of spines after the induction of long-term
      potentiation (LTP). Using two-photon time-lapse imaging of dendritic spines in
      acute hippocampal slices from neonatal rats, we found that the induction of long
      term depression (LTD) by low-frequency stimulation is accompanied by a marked
      shrinkage of spines, which can be reversed by subsequent high-frequency
      stimulation that induces LTP. The spine shrinkage requires activation of NMDA
      receptors and calcineurin, similar to that for LTD. However, spine shrinkage is
      mediated by cofilin, but not by protein phosphatase 1 (PP1), which is essential
      for LTD, suggesting that different downstream pathways are involved in spine
      shrinkage and LTD. This activity-induced spine shrinkage may contribute to
      activity-dependent elimination of synaptic connections.

PMID- 15572108
TI  - Bidirectional activity-dependent morphological plasticity in hippocampal neurons.
AB  - Dendritic spines on pyramidal neurons receive the vast majority of excitatory
      input and are considered electrobiochemical processing units, integrating and
      compartmentalizing synaptic input. Following synaptic plasticity, spines can
      undergo morphological plasticity, which possibly forms the structural basis for
      long-term changes in neuronal circuitry. Here, we demonstrate that spines on CA1
      pyramidal neurons from organotypic slice cultures show bidirectional activity
      dependent morphological plasticity. Using two-photon time-lapse microscopy, we
      observed that low-frequency stimulation induced NMDA receptor-dependent spine
      retractions, whereas theta burst stimulation led to the formation of new spines.
      Moreover, without stimulation the number of spine retractions was on the same
      order of magnitude as the stimulus-induced spine gain or loss. Finally, we found
      that the ability of neurons to eliminate spines in an activity-dependent manner
      decreased with developmental age. Taken together, our data show that hippocampal
      neurons can undergo bidirectional morphological plasticity; spines are formed and
      eliminated in an activity-dependent way.

PMID- 15572109
TI  - Functional recovery in a primate model of Parkinson's disease following motor
      cortex stimulation.
AB  - A concept in Parkinson's disease postulates that motor cortex may pattern
      abnormal rhythmic activities in the basal ganglia, underlying the genesis of
      observed motor symptoms. We conducted a preclinical study of electrical
      interference in the primary motor cortex using a chronic MPTP primate model in
      which dopamine depletion was progressive and regularly documented using 18F-DOPA
      positron tomography. High-frequency motor cortex stimulation significantly
      reduced akinesia and bradykinesia. This behavioral benefit was associated with an
      increased metabolic activity in the supplementary motor area as assessed with 18
      F-deoxyglucose PET, a normalization of mean firing rate in the internal globus
      pallidus (GPi) and the subthalamic nucleus (STN), and a reduction of synchronized
      oscillatory neuronal activities in these two structures. Motor cortex stimulation
      is a simple and safe procedure to modulate subthalamo-pallido-cortical loop and
      alleviate parkinsonian symptoms without requiring deep brain stereotactic
      surgery.

PMID- 15572110
TI  - Rho GTPases regulate axon growth through convergent and divergent signaling
      pathways.
AB  - Rho GTPases are essential regulators of cytoskeletal reorganization, but how they
      do so during neuronal morphogenesis in vivo is poorly understood. Here we show
      that the actin depolymerization factor cofilin is essential for axon growth in
      Drosophila neurons. Cofilin function in axon growth is inhibited by LIM kinase
      and activated by Slingshot phosphatase. Dephosphorylating cofilin appears to be
      the major function of Slingshot in regulating axon growth in vivo. Genetic data
      provide evidence that Rho or Rac/Cdc42, via effector kinases Rok or Pak,
      respectively, activate LIM kinase to inhibit axon growth. Importantly, Rac also
      activates a Pak-independent pathway that promotes axon growth, and different
      RacGEFs regulate these distinct pathways. These genetic analyses reveal
      convergent and divergent pathways from Rho GTPases to the cytoskeleton during
      axon growth in vivo and suggest that different developmental outcomes could be
      achieved by biases in pathway selection.

PMID- 15572111
TI  - Extracellular proteins organize the mechanosensory channel complex in C. elegans
      touch receptor neurons.
AB  - Specialized extracellular matrix (ECM) is associated with virtually every
      mechanosensory system studied. C. elegans touch receptor neurons have specialized
      ECM and attach to the surrounding epidermis. The mec-1 gene encodes an ECM
      protein with multiple EGF and Kunitz domains. MEC-1 is needed for the
      accumulation of the collagen MEC-5 and other ECM components, attachment, and,
      separately, for touch sensitivity. MEC-1 and MEC-5 bind to touch processes
      uniformly and in puncta. These puncta colocalize with and localize the
      mechanosensory channel complex in the touch neurons. In turn, the production of
      the MEC-1 and MEC-5 puncta appears to rely on interactions with the neighboring
      epidermal tissue. These and other observations lead us to propose that
      extracellular, but not cytoskeletal, tethering of the degenerin channel is needed
      for mechanosensory transduction. Additionally, our experiments demonstrate an
      important role of the ECM in organizing the placement of the channel complex.

PMID- 15572112
TI  - Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with
      PAF-acetylhydrolase.
AB  - Mutations in the LIS1 gene cause lissencephaly, a human neuronal migration
      disorder. LIS1 binds dynein and the dynein-associated proteins Nde1 (formerly
      known as NudE), Ndel1 (formerly known as NUDEL), and CLIP-170, as well as the
      catalytic alpha dimers of brain cytosolic platelet activating factor
      acetylhydrolase (PAF-AH). The mechanism coupling the two diverse regulatory
      pathways remains unknown. We report the structure of LIS1 in complex with the
      alpha2/alpha2 PAF-AH homodimer. One LIS1 homodimer binds symmetrically to one
      alpha2/alpha2 homodimer via the highly conserved top faces of the LIS1 beta
      propellers. The same surface of LIS1 contains sites of mutations causing
      lissencephaly and overlaps with a putative dynein binding surface. Ndel1 competes
      with the alpha2/alpha2 homodimer for LIS1, but the interaction is complex and
      requires both the N- and C-terminal domains of LIS1. Our data suggest that the
      LIS1 molecule undergoes major conformational rearrangement when switching from a
      complex with the acetylhydrolase to the one with Ndel1.

PMID- 15572113
TI  - A conserved tripeptide in CNG and HCN channels regulates ligand gating by
      controlling C-terminal oligomerization.
AB  - Cyclic nucleotides directly enhance the opening of the tetrameric CNG and HCN
      channels, although the mechanism remains unclear. We examined why HCN and certain
      CNG subunits form functional homomeric channels, whereas other CNG subunits only
      function in heteromeric channels. The "defect" in the CNGA4 subunit that prevents
      its homomeric expression was localized to its C-linker, which connects the
      transmembrane domain to the binding domain and contains a tripeptide that
      decreases the efficacy of ligand gating. Remarkably, replacement of the
      homologous HCN tripeptide with the CNGA4 sequence transformed cAMP into an
      inverse agonist that inhibits HCN channel opening. Using analytical
      ultracentrifugation, we identified the structural basis for this gating switch:
      whereas cAMP normally enhances the assembly of HCN C-terminal domains into a
      tetrameric gating ring, inclusion of the CNGA4 tripeptide reversed this action so
      that cAMP now causes gating ring disassembly. Thus, ligand gating depends on the
      dynamic oligomerization of C-terminal binding domains.

PMID- 15572114
TI  - Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during
      uncorrelated activity.
AB  - The plasticity of synapses within neural circuits is regulated by activity, but
      the underlying mechanisms remain elusive. Using the dye FM1-43 to directly image
      presynaptic function, we found that large numbers of presynaptic terminals in
      hippocampal cultures have a low release probability. While these terminals were
      not readily modifiable, a transient but not permanent long-term reduction of
      network activity or Ca2+ influx could increase their modifiability. This
      modulation of plasticity was mediated by Ca2+ flux through NMDA and voltage-gated
      calcium channels and was lost within 48 hr. A more permanent enhancement of
      synaptic plasticity was achieved by selectively reducing the Ca2+ flux associated
      with uncorrelated activity via adjustment of the voltage-dependent Mg2+ block of
      the NMDAR. Upregulation of NR2B-containing NMDARs induced by this treatment is an
      important but not sole contributor to the enhancement of plasticity. Thus,
      quantity and quality of activity have differential effects on the intrinsic
      plasticity of neurons.

PMID- 15572115
TI  - A developmental switch in the excitability and function of the starburst network
      in the mammalian retina.
AB  - Dual patch-clamp recording and Ca2+ uncaging revealed Ca2+-dependent corelease of
      ACh and GABA from, and the presence of reciprocal nicotinic and GABAergic
      synapses between, starburst cells in the perinatal rabbit retina. With
      maturation, the nicotinic synapses between starburst cells dramatically
      diminished, whereas the GABAergic synapses remained and changed from excitatory
      to inhibitory, indicating a coordinated conversion of the starburst network
      excitability from an early hyperexcitatory to a mature nonepileptic state. We
      show that this transition allows the starburst cells to use their
      neurotransmitters for two completely different functions. During early
      development, the starburst network mediates recurrent excitation and spontaneous
      retinal waves, which are important for visual system development. After vision
      begins, starburst cells release GABA in a prolonged and Ca2+-dependent manner and
      inhibit each other laterally via direct GABAergic synapses, which may be
      important for visual integration, such as the detection of motion direction.

PMID- 15572116
TI  - Maintaining accuracy at the expense of speed: stimulus similarity defines odor
      discrimination time in mice.
AB  - Odor discrimination times and their dependence on stimulus similarity were
      evaluated to test temporal and spatial models of odor representation in mice. In
      a go/no-go operant conditioning paradigm, discrimination accuracy and time were
      determined for simple monomolecular odors and binary mixtures of odors. Mice
      discriminated simple odors with an accuracy exceeding 95%. Binary mixtures
      evoking highly overlapping spatiotemporal patterns of activity in the olfactory
      bulb were discriminated equally well. However, while discriminating simple odors
      in less than 200 ms, mice required 70-100 ms more time to discriminate highly
      similar binary mixtures. We conclude that odor discrimination in mice is fast and
      stimulus dependent. Thus, the underlying neuronal mechanisms act on a fast
      timescale, requiring only a brief epoch of odor-specific spatiotemporal
      representations to achieve rapid discrimination of dissimilar odors. The fine
      discrimination of highly similar stimuli, however, requires temporal integration
      of activity, suggesting a tradeoff between accuracy and speed.

PMID- 15572117
TI  - Prediction error during retrospective revaluation of causal associations in
      humans: fMRI evidence in favor of an associative model of learning.
AB  - Associative learning theory assumes that prediction error is a driving force in
      learning. A competing view, probabilistic contrast (PC) theory, is that learning
      and prediction error are unrelated. We tested a learning phenomenon that has
      proved troublesome for associative theory--retrospective revaluation--to evaluate
      these two models. We previously showed that activation in right lateral
      prefrontal cortex (PFC) provides a reliable signature for the presence of
      prediction error. Thus, if the associative view is correct, retrospective
      revaluation should be accompanied by right lateral PFC activation. PC theory
      would be supported by the absence of this activation. Right PFC and ventral
      striatal activation occurred during retrospective revaluation, supporting the
      associative account. Activations appeared to reflect the degree of revaluation,
      predicting later brain responses to revalued cues. Our results support a modified
      associative account of retrospective revaluation and demonstrate the potential of
      functional neuroimaging as a tool for evaluating competing learning models.

PMID- 15572118
TI  - Face perception: domain specific, not process specific.
AB  - Evidence that face perception is mediated by special cognitive and neural
      mechanisms comes from fMRI studies of the fusiform face area (FFA) and behavioral
      studies of the face inversion effect. Here, we used these two methods to ask
      whether face perception mechanisms are stimulus specific, process specific, or
      both. Subjects discriminated pairs of upright or inverted faces or house stimuli
      that differed in either the spatial distance among parts (configuration) or the
      shape of the parts. The FFA showed a much higher response to faces than to
      houses, but no preference for the configuration task over the part task.
      Similarly, the behavioral inversion effect was as large in the part task as the
      configuration task for faces, but absent in both part and configuration tasks for
      houses. These findings indicate that face perception mechanisms are not process
      specific for parts or configuration but are domain specific for face stimuli per
      se.

PMID- 15572119
TI  - Born again at the synapse: a new function for the anaphase promoting
      complex/cyclosome.
AB  - Currently, perhaps the most significant biological problem is to understand the
      mechanisms of learning and memory, and many of the answers will come from
      molecular explanations of synaptic plasticity. Two new papers have established a
      surprising connection: the Anaphase Promoting Complex/Cyclosome (APC/C) has a
      second function in controlling local protein stability at synapses, and hence in
      the control of behavior .

PMID- 15572120
TI  - A new cytoskeletal connection for APC: linked to actin through IQGAP.
AB  - Migrating cells reorganize their actin and microtubule cytoskeletons in response
      to external cues. In this issue of Developmental Cell, Watanabe et al. now show a
      molecular connection between the actin crosslinking protein IQGAP1 and the
      microtubule-stabilizing protein APC that impacts cells' ability to migrate into a
      wound.

PMID- 15572121
TI  - Nuclear pore complex structure: unplugged and dynamic pores.
AB  - Nuclear pore complexes (NPCs) are large protein assemblies embedded in the
      nuclear envelope that act as passageways for transport of molecules into and out
      of the nucleus. Two new studies, one in Nature Cell Biology and one in Science ,
      offer direct evidence that the NPC is a highly dynamic structure.

PMID- 15572122
TI  - On the InterAktion between hexokinase and the mitochondrion.
AB  - The protein kinase Akt is now well recognized as a potent inhibitor of apoptosis.
      Work published by Majewski et al. in the December 3rd issue of Molecular Cell
      indicates that a major pathway by which Akt suppresses cell death is by
      stimulating the translocation of hexokinase to the mitochondrion. Hexokinase, in
      turn, antagonizes the release of mitochondrial cytochrome C.

PMID- 15572123
TI  - The versatile roles of "axon guidance" cues in tissue morphogenesis.
AB  - The Netrin, Slit, Semaphorin, and Ephrin families of secreted proteins were
      originally characterized in the nervous system as guidance cues for axons;
      however, recent studies demonstrate that many members of these families
      contribute to the development of a variety of organs. Here, the current knowledge
      of their roles is discussed with a focus on four tissues: lung, mammary,
      cardiovascular, and kidney. While many studies indicate a role for "axon
      guidance" cues in regulating cell-cell and cell-extracellular matrix (ECM)
      interactions during organogenesis, there is accumulating evidence that they also
      contribute to tissue development by regulating the transcription and translation
      of genes encoding key morphogenetic factors.

PMID- 15572124
TI  - The oxidative burst at fertilization is dependent upon activation of the dual
      oxidase Udx1.
AB  - The sea urchin egg is a quiescent cell...until fertilization, when the egg is
      activated. The classic respiratory burst at fertilization is the result of
      prodigious hydrogen peroxide production, but the mechanism for this synthesis is
      not known. Here we quantitate the kinetics of hydrogen peroxide synthesis at a
      single-cell level using an imaging photon detector, showing that 60 nM hydrogen
      peroxide accumulates within the perivitelline space of each zygote. We find that
      the NADPH oxidation activity is enriched at the cell surface and is sensitive to
      a pharmacological inhibitor of NADPH oxidase enzymes. Finally, we show that a sea
      urchin dual oxidase homolog, Udx1, is responsible for generating the hydrogen
      peroxide necessary for the physical block to polyspermy. Phylogenetic analysis of
      the enzymatic modules in Udx1 suggests a potentially conserved role for the dual
      oxidase family in hydrogen peroxide production and regulation during
      fertilization.

PMID- 15572125
TI  - Centriole assembly requires both centriolar and pericentriolar material proteins.
AB  - Centrioles organize pericentriolar material to form centrosomes and also template
      the formation of cilia. Despite the importance of centrioles in dividing and
      differentiated cells, their assembly remains poorly understood at a molecular
      level. Here, we develop a fluorescence microscopy-based assay for centriole
      assembly in the 1-cell stage C. elegans embryo. We use this assay to characterize
      SAS-6, a centriolar protein that we identified based on its requirement for
      centrosome duplication. We show that SAS-6, a member of a conserved metazoan
      protein family, is specifically required for new centriole assembly, a result we
      confirm by electron microscopy. We further use the centriole assembly assay to
      examine the roles of three pericentriolar material proteins: SPD-5, the kinase
      aurora-A, and gamma-tubulin. Our results suggest that the pericentriolar material
      promotes daughter centriole formation by concentrating gamma-tubulin around the
      parent centriole. Thus, both centriolar and pericentriolar material proteins
      contribute to centriole assembly.

PMID- 15572126
TI  - Multiple Wnt signaling pathways converge to orient the mitotic spindle in early
      C. elegans embryos.
AB  - How cells integrate the input of multiple polarizing signals during division is
      poorly understood. We demonstrate that two distinct Caenorhabditis elegans Wnt
      pathways contribute to the polarization of the ABar blastomere by differentially
      regulating its duplicated centrosomes. Contact with the C blastomere orients the
      ABar spindle through a nontranscriptional Wnt spindle alignment pathway, while a
      Wnt/beta-catenin pathway controls the timing of ABar spindle rotation. The three
      C. elegans Dishevelled homologs contribute to these processes in different ways,
      suggesting that functional distinctions may exist among them. We also find that
      CKI (KIN-19) plays a role not only in the Wnt/beta-catenin pathway, but also in
      the Wnt spindle orientation pathway as well. Based on these findings, we
      establish a model for the coordination of cell-cell interactions and distinct Wnt
      signaling pathways that ensures the robust timing and orientation of spindle
      rotation during a developmentally regulated cell division event.

PMID- 15572127
TI  - Positive regulation of myogenic bHLH factors and skeletal muscle development by
      the cell surface receptor CDO.
AB  - Skeletal myogenesis is controlled by bHLH transcription factors of the MyoD
      family that, along with MEF-2 factors, comprise a positive feedback network that
      maintains the myogenic transcriptional program. Cell-cell contact between muscle
      precursors promotes myogenesis, but little is known of the underlying mechanisms.
      CDO, an Ig superfamily member, is a component of a cell surface receptor complex
      found at sites of cell-cell contact that positively regulates myogenesis in
      vitro. We report here that mice lacking CDO display delayed skeletal muscle
      development. Additionally, satellite cells from these mice differentiate
      defectively in vitro. CDO functions to activate myogenic bHLH factors via
      enhanced heterodimer formation, most likely by inducing hyperphosphorylation of E
      proteins. The Cdo gene is, in turn, a target of MyoD. The promyogenic effect of
      cell-cell contact is therefore linked to the activity of myogenic bHLH factors.
      Furthermore, the myogenic positive feedback network extends from the cell surface
      to the nucleus.

PMID- 15572128
TI  - RhoB and actin polymerization coordinate Src activation with endosome-mediated
      delivery to the membrane.
AB  - We have used a c-Src-GFP fusion protein to address the spatial control of Src
      activation and the nature of Src-associated intracellular structures during
      stimulus-induced transit to the membrane. Src is activated during transit,
      particularly in RhoB-containing cytoplasmic endosomes associated with the
      perinuclear recycling compartment. Knocking out RhoB or expressing a dominant
      interfering Rab11 mutant suppresses both catalytic activation of Src and
      translocation of active kinase to peripheral membrane structures. In addition,
      the Src- and RhoB-containing endosomes harbor proteins involved in actin
      polymerization and filament assembly, for example Scar1, and newly polymerized
      actin can associate with these endosomes in a Src-dependent manner. This implies
      that Src may regulate an endosome-associated actin nucleation activity. In
      keeping with this, Src controls the actin dependence of RhoB endosome movement
      toward the plasma membrane. This work identifies RhoB as a component of "outside
      in" signaling pathways that coordinate Src activation with translocation to
      transmembrane receptors.

PMID- 15572129
TI  - Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell
      polarization and migration.
AB  - Rho family GTPases, particularly Rac1 and Cdc42, are key regulators of cell
      polarization and directional migration. Adenomatous polyposis coli (APC) is also
      thought to play a pivotal role in polarized cell migration. We have found that
      IQGAP1, an effector of Rac1 and Cdc42, interacts directly with APC. IQGAP1 and
      APC localize interdependently to the leading edge in migrating Vero cells, and
      activated Rac1/Cdc42 form a ternary complex with IQGAP1 and APC. Depletion of
      either IQGAP1 or APC inhibits actin meshwork formation and polarized migration.
      Depletion of IQGAP1 or APC also disrupts localization of CLIP-170, a microtubule
      stabilizing protein that interacts with IQGAP1. Taken together, these results
      suggest a model in which activation of Rac1 and Cdc42 in response to migration
      signals leads to recruitment of IQGAP1 and APC which, together with CLIP-170,
      form a complex that links the actin cytoskeleton and microtubule dynamics during
      cell polarization and directional migration.

PMID- 15572130
TI  - EGF receptor signaling regulates pulses of cell delamination from the Drosophila
      ectoderm.
AB  - Many different intercellular signaling pathways are known but, for most, it is
      unclear whether they can generate oscillating cell behaviors. Here we use time
      lapse analysis of Drosophila embryogenesis to show that oenocytes delaminate from
      the ectoderm in discrete bursts of three. This pulsatile process has a 1 hour
      period, occurs without cell division, and requires a localized EGF receptor
      (EGFR) response. High-threshold EGFR targets are sequentially activated in rings
      of three cells, prefiguring the temporal pattern of delamination. Surprisingly,
      widespread misexpression of the relevant activating ligand, Spitz, is compatible
      with robust delamination pulses. Moreover, although Spitz ligand becomes limiting
      after only two pulses, artificially prolonging its secretion generates up to six
      additional cycles, revealing a rhythmic underlying mechanism. These findings
      illustrate how intercellular signaling and cell movements can generate multiple
      cycles of a cell behavior, despite individual cells experiencing only one cycle
      of receptor activation.

PMID- 15572131
TI  - The apical caspase dronc governs programmed and unprogrammed cell death in
      Drosophila.
AB  - Among the seven caspases encoded in the fly genome, only dronc contains a caspase
      recruitment domain. To assess the function of this gene in development, we
      produced a null mutation in dronc. Animals lacking zygotic dronc are defective
      for programmed cell death (PCD) and arrest as early pupae. These mutants present
      a range of defects, including extensive hyperplasia of hematopoietic tissues,
      supernumerary neuronal cells, and head involution failure. dronc genetically
      interacts with the Ced4/Apaf1 counterpart, Dark, and adult structures lacking
      dronc are disrupted for fine patterning. Furthermore, in diverse models of
      metabolic injury, dronc- cells are completely insensitive to induction of cell
      killing. These findings establish dronc as an essential regulator of cell number
      in development and illustrate broad requirements for this apical caspase in
      adaptive responses during stress-induced apoptosis.

PMID- 15572132
TI  - Drosophila caspase DRONC is required for specific developmental cell death
      pathways and stress-induced apoptosis.
AB  - Proteases of the caspase family play key roles in the execution of apoptosis. In
      Drosophila there are seven caspases, but their roles in cell death have not been
      studied in detail due to a lack of availability of specific mutants. Here, we
      describe the generation of a specific mutant of the Drosophila gene encoding
      DRONC, the only caspase recruitment domain (CARD) containing apical caspase in
      the fly. dronc mutants are pupal lethal and our studies show that DRONC is
      required for many forms of developmental cell deaths and apoptosis induced by DNA
      damage. Furthermore, we demonstrate that DRONC is required for the autophagic
      death of larval salivary glands during metamorphosis, but not for histolysis of
      larval midguts. Our results indicate that DRONC is involved in specific
      developmental cell death pathways and that in some tissues, effector caspase
      activation and cell death can occur independently of DRONC.

PMID- 15572133
TI  - Zebrafish slow muscle cell migration induces a wave of fast muscle morphogenesis.
AB  - The specification and morphogenesis of slow and fast twitch muscle fibers are
      crucial for muscle development. In zebrafish, Hedgehog is required for slow
      muscle fiber specification. However, less is known about signals that promote
      development of fast muscle fibers, which constitute the majority of somitic
      cells. We show that when Hedgehog signaling is blocked, fast muscle cell
      elongation is disrupted. Using genetic mosaics, we show that Hedgehog signal
      perception is required by slow muscle cells but not by fast muscle cells for fast
      muscle cell elongation. Furthermore, we show that slow muscle cells are
      sufficient to pattern the medial to lateral wave of fast muscle fiber
      morphogenesis even when fast muscle cells cannot perceive the Hedgehog signal.
      Thus, the medial to lateral migration of slow muscle fibers through the somite
      creates a morphogenetic signal that patterns fast muscle fiber elongation in its
      wake.

PMID- 15572134
TI  - Visualization of trans-homolog enhancer-promoter interactions at the Abd-B Hox
      locus in the Drosophila embryo.
AB  - The Hox gene Abdominal-B (Abd-B) controls the morphogenesis of posterior
      abdominal segments in Drosophila. Expression is regulated by a series of 3'
      enhancers that are themselves transcribed. RNA FISH was used to visualize nascent
      transcripts associated with coding and noncoding regions of Abd-B in developing
      embryos. Confocal imaging suggests that distal enhancers often loop to the Abd-B
      promoter region. Surprisingly, enhancers located on one chromosome frequently
      associate with the Abd-B transcription unit located on the other homolog. These
      trans-homolog interactions can be interpreted as the direct visualization of a
      genetic phenomenon known as transvection, whereby certain mutations in Abd-B can
      be rescued in trans by the other copy of the gene. A 10 kb sequence in the 3'
      flanking region mediates tight pairing of Abd-B alleles, thereby facilitating
      trans looping of distal enhancers. Such trans-homolog interactions might be a
      common mechanism of gene regulation in higher metazoans.

PMID- 15572135
TI  - The evolutionary origin of cardiac chambers.
AB  - Identification of cardiac mechanisms of retinoic acid (RA) signaling, description
      of homologous genetic circuits in Ciona intestinalis and consolidation of views
      on the secondary heart field have fundamental, but still unrecognized
      implications for vertebrate heart evolution. Utilizing concepts from evolution,
      development, zoology, and circulatory physiology, we evaluate the strengths of
      animal models and scenarios for the origin of vertebrate hearts. Analyzing
      chordates, lower and higher vertebrates, we propose a paradigm picturing
      vertebrate hearts as advanced circulatory pumps formed by segments, chambered or
      not, devoted to inflow or outflow. We suggest that chambers arose not as single
      units, but as components of a peristaltic pump divided by patterning events,
      contrasting with scenarios assuming that chambers developed one at a time.
      Recognizing RA signaling as a potential mechanism patterning cardiac segments, we
      propose to use it as a tool to scrutinize the phylogenetic origins of cardiac
      chambers within chordates. Finally, we integrate recent ideas on cardiac
      development such as the ballooning and secondary/anterior heart field paradigms,
      showing how inflow/outflow patterning may interact with developmental mechanisms
      suggested by these models.

PMID- 15572136
TI  - Sexual selection, genetic conflict, selfish genes, and the atypical patterns of
      gene expression in spermatogenic cells.
AB  - This review proposes that the peculiar patterns of gene expression in
      spermatogenic cells are the consequence of powerful evolutionary forces known as
      sexual selection. Sexual selection is generally characterized by intense
      competition of males for females, an enormous variety of the strategies to
      maximize male reproductive success, exaggerated male traits at all levels of
      biological organization, co-evolution of sexual traits in males and females, and
      conflict between the sexual advantage of the male trait and the reproductive
      fitness of females and the individual fitness of both sexes. In addition,
      spermatogenesis is afflicted by selfish genes that promote their transmission to
      progeny while causing deleterious effects. Sexual selection, selfish genes, and
      genetic conflict provide compelling explanations for many atypical features of
      gene expression in spermatogenic cells including the gross overexpression of
      certain mRNAs, transcripts encoding truncated proteins that cannot carry out
      basic functions of the proteins encoded by the same genes in somatic cells, the
      large number of gene families containing paralogous genes encoding spermatogenic
      cell-specific isoforms, the large number of testis-cancer-associated genes that
      are expressed only in spermatogenic cells and malignant cells, and the
      overbearing role of Sertoli cells in regulating the number and quality of
      spermatozoa.

PMID- 15572137
TI  - The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival
      and differentiation in the inner ear and lateral line.
AB  - To understand the molecular basis of sensory organ development and disease, we
      have cloned and characterized the zebrafish mutation dog-eared (dog) that is
      defective in formation of the inner ear and lateral line sensory systems. The dog
      locus encodes the eyes absent-1 (eya1) gene and single point mutations were found
      in three independent dog alleles, each prematurely truncating the expressed
      protein within the Eya domain. Moreover, morpholino-mediated knockdown of eya1
      gene function phenocopies the dog-eared mutation. In zebrafish, the eya1 gene is
      widely expressed in placode-derived sensory organs during embryogenesis but Eya1
      function appears to be primarily required for survival of sensory hair cells in
      the developing ear and lateral line neuromasts. Increased levels of apoptosis
      occur in the migrating primordia of the posterior lateral line in dog embryos and
      as well as in regions of the developing otocyst that are mainly fated to give
      rise to sensory cells of the cristae. Importantly, mutation of the EYA1 or EYA4
      gene causes hereditary syndromic deafness in humans. Determination of eya gene
      function during zebrafish organogenesis will facilitate understanding the
      molecular etiology of human vestibular and hearing disorders.

PMID- 15572138
TI  - cDermo-1 misexpression induces dense dermis, feathers, and scales.
AB  - Reciprocal epithelio-mesenchymal interactions between the prospective epidermis
      and the underlying dermis are the major driving forces in the development of skin
      appendages. Feather development is initiated by a still unknown signal from the
      dermis in feather-forming skin. The morphological response of the ectoderm to
      this signal is the formation of an epidermal placode, which signals back to the
      mesenchyme to induce dermal condensations. Together, epidermal and dermal
      components constitute the outgrowing feather bud. The bHLH transcription factor
      cDermo-1 is expressed in developing dermis and is the earliest known marker of
      prospective feather tracts. To test its function during feather development, we
      forced cDermo-1 expression in embryonic chicken dermis using a retroviral
      expression vector. In featherless (apteric) regions, cDermo-1 misexpression
      induced dense, thickened dermis normally observed in feathered skin (pterylae),
      and leads to the development of regularly spaced and normally shaped ectopic
      feather buds. In pterylae, cDermo-1 misexpression enhanced feather growth. In
      hindlimb skin, according to the local skin identity, misexpression of cDermo-1
      induced ectopic scale formation. Thus, we show that forced cDermo-1 expression in
      developing dermis is sufficient to launch the developmental program leading to
      skin appendage formation. We propose a role of cDermo-1 at the initial stages of
      feather induction upstream of FGF10.

PMID- 15572139
TI  - Temporal modulation of the Hedgehog morphogen gradient by a patched-dependent
      targeting to lysosomal compartment.
AB  - Morphogenetic gradient of Hh is tightly regulated for correct patterning in
      Drosophila and vertebrates. The Patched (Ptc) receptor is required for
      restricting Hh long-range activity in the imaginal discs. In this study, we
      investigate the different types of Hh accretion that can be observed in the
      Drosophila embryonic epithelial cells. We found that, in receiving cells, large
      apical punctate structures of Hh (Hh-LPSs) are not depending on the Ptc receptor
      dependent internalization of Hh but rather reflect Hh gradient. By analyzing the
      dynamic of the Hh-LPS gradient formation, we demonstrate that Hh distribution is
      strongly restricted during late embryonic stages compared to earlier stages. We
      demonstrate that the up-regulation of Ptc is required for the temporal regulation
      of the Hh gradient. We further show that dynamin-dependent internalization of Hh
      is not regulating Hh spreading but is involved in shaping Hh gradient. We found
      that Hh gradient modulation is directly related with the dynamic expression of
      the ventral Hh target gene serrate (ser) and with the Hh-dependent dorsal cell
      fate determination. Finally, our study shows that, in vivo, the Hh/Ptc complex is
      internalized in the Rab7-enriched lysosomal compartment in a Ptc-dependent manner
      without the co-receptor Smoothened (Smo). We propose that controlled degradation
      is an active mechanism important for Hh gradient formation.

PMID- 15572140
TI  - Neural crest cell origin for intrinsic ganglia of the developing chicken lung.
AB  - The development of intrinsic ganglia, comprised of neurons and glia cells that
      innervate airway smooth muscle, is a recognized component of the growing lung.
      However, the embryological origin of these neurons and glia is unclear. The lung
      buds develop as an outgrowth of the foregut, which contains migrating neural
      crest cells (NCC) that ultimately give rise to the enteric nervous system (ENS)
      along the entire length of the gut. It has therefore been proposed that the
      intrinsic ganglia of the lung arise from a subset of NCC that leave the gut and
      migrate into the lung buds during early development. We have tested this
      hypothesis using quail-chick interspecies grafting to selectively label the
      hindbrain-derived neural crest cell population that colonizes the gut. In
      conjunction with antibody labeling and in situ hybridization, we demonstrate
      that: (i) lung ganglia arise from vagal NCC that migrate from the foregut into
      the lung buds; (ii) like ENS precursors, these NCC express the transcription
      factor Sox10, and the receptors EDNRB and RET; (iii) the co-receptor for RET,
      GFRalpha1, is expressed in the lung mesenchyme and in ganglia; (iv) ganglia
      persist within the lung throughout development and contain cells immunopositive
      for the pan-neuronal markers ANNA-1 and PGP9.5, the inhibitory neurotransmitter
      NO, as shown by NADPH-diaphorase staining, and the glial marker GFAP.

PMID- 15572141
TI  - Regulation of NF-kappaB/Rel by IkappaB is essential for ascidian notochord
      formation.
AB  - We previously reported that two NF-kappaB/Rel family members are involved in
      notochord formation of the ascidian Halocynthia roretzi. Here, we present
      evidence that the NF-kappaB/Rel signaling pathway plays important roles in the
      notochord formation in another ascidian, Ciona intestinalis. We first found that
      two NF-kappaB/Rel family members of C. intestinalis, Ci-rel1 and Ci-rel2, are
      splice variants: Ci-rel1 is a typical member, while Ci-rel2 is a C-terminally
      truncated short one. Ectopic expression of GFP-fusion proteins in the C.
      intestinalis notochord revealed that Ci-rel1 transiently moved into the nucleus
      in the initial tailbud stage, when concomitant expression of Ci-IkappaB, a C.
      intestinalis IkappaB homologue, was observed, indicating that Ci-rel1 is
      transiently activated in this stage. Ci-rel1, as well as Ci-rel2, is capable of
      binding to the kappaB sequence present upstream of Ci-IkappaB, suggesting that Ci
      IkappaB is a target gene of Ci-rel1. Reporter gene assay suggests that the
      expression of Ci-IkappaB in the notochord is controlled by its kappaB sequence.
      Gene silencing of Ci-IkappaB by injection of the corresponding antisense
      morpholino oligonucleotide resulted in impairment of notochord formation in C.
      intestinalis, particularly in a defect in intercalation of notochord cells. Taken
      together, the results suggest that the regulation of Ci-rel1 by Ci-IkappaB, whose
      transcription is regulated by Ci-rel1, in the tailbud stage is essential for
      notochord formation in C. intestinalis.

PMID- 15572142
TI  - Belle is a Drosophila DEAD-box protein required for viability and in the germ
      line.
AB  - DEAD-box proteins are ATP-dependent RNA helicases that function in various stages
      of RNA processing and in RNP remodeling. Here, we report identification and
      characterization of the Drosophila protein Belle (Bel), which belongs to a highly
      conserved subfamily of DEAD-box proteins including yeast Ded1p, Xenopus An3,
      mouse PL10, human DDX3/DBX, and human DBY. Mutations in DBY are a frequent cause
      of male infertility in humans. Bel can substitute in vivo for Ded1p, an essential
      yeast translation factor, suggesting a requirement for Bel in translation
      initiation. Consistent with an essential cellular function, strong loss of
      function mutations in bel are recessive lethal with a larval growth defect
      phenotype. Hypomorphic bel mutants are male-sterile. Bel is also closely related
      to the Drosophila DEAD-box protein Vasa (Vas), a germ line-specific translational
      regulator. We find that Bel and Vas colocalize in nuage and at the oocyte
      posterior during oogenesis, and that bel function is required for female
      fertility. However, unlike Vas, Bel is not specifically enriched in embryonic
      pole cells. We conclude that the DEAD-box protein Bel has evolutionarily
      conserved roles in fertility and development.

PMID- 15572143
TI  - The cellular and molecular etiology of the cleft secondary palate in Fgf10 mutant
      mice.
AB  - Mammalian palatogenesis depends on interactions between the stomodium-derived
      epithelium and the cranial neural crest-derived ectomesenchyme. Fibroblast growth
      factor 10 (FGF10) is a mesenchymal signaling factor that guides the morphogenesis
      of multiple organs through tissue-tissue interactions. This is consistent with
      widespread agenesis and dysgenesis of organs observed in Fgf10-/- mice. In this
      study, we report the presence of a wide-open cleft secondary palate in Fgf10
      homozygous null mutant mice. Fgf10 transcripts were detected in the palatal
      mesenchyme from E11.5 to E13.5 during normal palatogenesis and were enriched in
      the anterior and middle portions of the palatal shelves. In Fgf10-/- embryos,
      histological analyses revealed aberrant adhesion of the palatal shelves with the
      tongue in the anterior and fusion with the mandible in the middle and posterior
      beginning at E13.5, which could prevent normal elevation of the palatal shelves
      leading to a cleft palate. TUNEL and BrdU assays demonstrated significant levels
      of apoptosis in the medial edge epithelium (MEE) but unaltered cell proliferation
      in mutant palatal shelves. At the molecular level, we show that Fgf10 is
      epistatic to Jagged2 and Tgfbeta3 in the developing palate. Notably, the
      expression of Jagged2 is downregulated throughout the palate epithelium in Fgf10
      mutants while Tgfbeta3 is misexpressed in the palatal epithelium at the oral
      side. Our results demonstrate that mesenchymally expressed Fgf10 is necessary for
      the survival of MEE cells and for the normal expression of Jagged2 and Tgfbeta3
      in the palatal epithelium during mammalian palatogenesis.

PMID- 15572144
TI  - Mkp3 is a negative feedback modulator of Fgf8 signaling in the mammalian isthmic
      organizer.
AB  - The pivotal mechanisms that govern the correct patterning and regionalization of
      the distinct areas of the mammalian CNS are driven by key molecules that emanate
      from the so-called secondary organizers at neural plate and tube stages. FGF8 is
      the candidate morphogenetic molecule to pattern the mesencephalon and
      rhombencephalon in the isthmic organizer (IsO). Recognizable relevance has been
      given to the intracellular pathways by which Fgf8 is regulated and modulated. In
      chick limb bud development, a dual mitogen-activated protein kinase phosphatase-3
      (Mkp3) plays a role as a negative feedback modulator of Fgf8 signaling. We have
      investigated the role of Mkp3 and its functional relationship with the Fgf8
      signaling pathway in the mouse IsO using gene transfer microelectroporation
      assays and protein-soaked bead experiments. Here, we demonstrate that MKP3 has a
      negative feedback action on the MAPK/ERK-mediated FGF8 pathway in the mouse
      neuroepithelium.

PMID- 15572145
TI  - Role of Yes kinase during early zebrafish development.
AB  - We have identified the Yes kinase in zebrafish eggs and investigated its role in
      development of the zebrafish embryo. In situ hybridization as well as
      immunofluorescence techniques demonstrated that Yes kinase is maternally
      expressed and is localized to the cortical region of the unfertilized egg.
      Fertilization resulted in concentration of Yes kinase to the blastodisc where it
      continued to be localized to the blastoderm cells through cleavage, gastrulation,
      and later development. Yes kinase activity was found to decrease abruptly at
      fertilization, then increase progressively during epiboly, and was maintained at
      high levels throughout gastrulation. The role of Yes kinase in development was
      tested by treating embryos with chemical protein tyrosine kinase (PTK) inhibitors
      such as 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2)
      and by injection of antisense morpholinos. Both treatments resulted in the arrest
      of development at the beginning of the epiboly. Co-immunoprecipitation studies
      demonstrated that Yes kinase participates in a stable complex with focal adhesion
      kinase (FAK), which is phosphorylated in vitro. These results demonstrate that
      Yes kinase plays an important role in epiboly and indicate that Yes kinase
      participates in signaling by focal adhesion kinase during early development.

PMID- 15572146
TI  - Caenorhabditis elegans DAZ-1 is expressed in proliferating germ cells and directs
      proper nuclear organization and cytoplasmic core formation during oogenesis.
AB  - The deleted in azoospermia (DAZ) family genes encode potential RNA-binding
      proteins that are expressed exclusively in germ cells in a wide range of
      metazoans. We have previously shown that mutations in daz-1, the only DAZ family
      gene in Caenorhabditis elegans, cause pachytene stage arrest of female germ cells
      but do not affect spermatogenesis. In this study, we report that DAZ-1 protein is
      most abundantly expressed in proliferating female germ cells, in a manner
      independent of the GLP-1 signaling pathway. DAZ-1 is dispensable in males but it
      is expressed also in male mitotic germ cells. Detailed phenotypic analyses with
      fluorescence microscopy and transmission electron microscopy have revealed that
      loss of daz-1 function causes multiple abnormalities as early as the onset of
      meiotic prophase, which include aberrant chromatin structure, small nucleoli,
      absence of the cytoplasmic core, and precocious cellularization. Although the
      reduced size of nucleoli is indicative of a low translational activity in these
      cells, artificial repression of general translation in the germline does not
      phenocopy the daz-1 mutant. Thus, we propose that DAZ-1 in C. elegans plays
      essential roles in female premeiotic and early meiotic germ cells, probably via
      regulating the translational activity of specific target genes required for the
      progression of oogenesis.

PMID- 15572147
TI  - Identification of Sox8 as a modifier gene in a mouse model of Hirschsprung
      disease reveals underlying molecular defect.
AB  - Mice carrying heterozygous mutations in the Sox10 gene display aganglionosis of
      the colon and represent a model for human Hirschsprung disease. Here, we show
      that the closely related Sox8 functions as a modifier gene for Sox10-dependent
      enteric nervous system defects as it increases both penetrance and severity of
      the defect in Sox10 heterozygous mice despite having no detectable influence on
      enteric nervous system development on its own. Sox8 exhibits an expression
      pattern very similar to Sox10 with occurrence in vagal and enteric neural crest
      cells and later confinement to enteric glia. Loss of Sox8 alleles in Sox10
      heterozygous mice impaired colonization of the gut by enteric neural crest cells
      already at early times. Whereas proliferation, apoptosis, and neuronal
      differentiation were normal for enteric neural crest cells in the gut of mutant
      mice, apoptosis was dramatically increased in vagal neural crest cells outside
      the gut. The defects in enteric nervous system development of mice with Sox10 and
      Sox8 mutations are therefore likely caused by a reduction of the pool of
      undifferentiated vagal neural crest cells. Our study suggests that Sox8 and Sox10
      are jointly required for the maintenance of these vagal neural crest stem cells.

PMID- 15572148
TI  - Differences in sensory projections between macro- and microchaetes in Drosophilid
      flies.
AB  - From examination of the central axonal projections of sensory bristles on the
      notum of several species of Drosophilidae, we demonstrate different features that
      may indicate different functions for macro- and microchaetes. The large
      macrochaetes have conserved arborizations that correlate with their conserved
      position. Nevertheless, we find evidence for only two discrete projection
      patterns for bristles in the dorsocentral (DC) row, even when there may be four
      or five bristles present. We show that the small microchaetes of Drosophila
      melanogaster display regional specificity and subsets of contiguous bristles
      project to a common region in the thoracic ganglion. Interestingly, the axons of
      each of these subsets also form a specific fasciculation group on the scutum
      before joining the axon of a particular macrochaete. The positions of
      microchaetes on the scutum and the shape of the fasciculation groups vary between
      closely related species. There is no correlation between body size, bristle
      patterns, and fasciculation patterns. Furthermore, none of these traits correlate
      with the phylogenetic relationships between the species studied. We discuss the
      possibility that macro- and microchaetes may have different functions and that
      these have implications for evolutionary constraints on bristle patterns.

PMID- 15572149
TI  - The axon guidance defect of the telencephalic commissures of the JSAP1-deficient
      brain was partially rescued by the transgenic expression of JIP1.
AB  - The JNK interacting protein, JSAP1, has been identified as a scaffold protein for
      mitogen-activated protein kinase (MAPK) signaling pathways and as a linker
      protein for the cargo transport along the axons. To investigate the physiological
      function of JSAP1 in vivo, we generated mice lacking JSAP1. The JSAP1 null
      mutation produced various developmental deficits in the brain, including an axon
      guidance defect of the corpus callosum, in which phospho-FAK and phospho-JNK were
      distributed at reduced levels. The axon guidance defect of the corpus callosum in
      the jsap1-/- brain was correlated with the misplacement of glial sling cells,
      which reverted to their normal position after the transgenic expression of JNK
      interacting protein 1(JIP1). The transgenic JIP1 partially rescued the axon
      guidance defect of the corpus callosum and the anterior commissure of the jsap1-/
      brain. The JSAP1 null mutation impaired the normal distribution of the Ca+2
      regulating protein, calretinin, but not the synaptic vesicle marker, SNAP-25,
      along the axons of the thalamocortical tract. These results suggest that JSAP1 is
      required for the axon guidance of the telencephalic commissures and the
      distribution of cellular protein(s) along axons in vivo, and that the signaling
      network organized commonly by JIP1 and JSAP1 regulates the axon guidance in the
      developing brain.

PMID- 15572150
TI  - Gonadogenesis in Pristionchus pacificus and organ evolution: development, adult
      morphology and cell-cell interactions in the hermaphrodite gonad.
AB  - The nematode gonad is an exemplary system for the study of organogenesis and
      fundamental problems in developmental and cellular biology. Nematode gonads vary
      dramatically across species (Chitwood, B.G., Chitwood, M.B., 1950. Introduction
      to Nematology." University Park Press, Baltimore; Felix, M.A., Sternberg, P.W.,
      1996. Symmetry breakage in the development of one-armed gonads in nematodes.
      Development 122, 2129-2142). As such, comparative developmental biology of
      gonadogenesis offers the potential to investigate changes in developmental and
      cellular processes that result in novel organ morphologies and thus may give
      insights into how these changes can affect animal bauplane. Pristionchus
      pacificus is a free-living nematode that diverged from the model nematode
      Caenorhabditis elegans around 200-300 million years ago. The morphology and
      development of P. pacificus is highly homologous to that of C. elegans. However,
      many differences in morphology and the underlying molecular signaling networks
      are easy to identify, making P. pacificus ideal for a comparative approach. Here,
      we report a detailed description of the P. pacificus hermaphrodite gonad using
      electron and fluorescent microscopy that will provide a basis for both phenotypic
      studies of genetic mutations and in vivo molecular studies of cloned genes
      involved in P. pacificus gonad development. We report that the morphology of the
      P. pacificus gonad is distinct from that of C. elegans. Among these differences
      are germ line patterning differences, heterochronic differences, novel gonadal
      arm-migrations, novel cellular composition of some somatic tissues (e.g., the
      number of cells that comprise the sheath and different spermathecal regions are
      different), the absence of a somatic tissue (e.g., the spermathecal valve cells),
      a novel architecture for the sheath, and changes in the cellular and sub-cellular
      morphology of the individual sheath cells. Additionally, we report a set of cell
      ablations in P. pacificus that indicate extensive cell communication between the
      somatic gonadal tissues and the germ line. Individual ablation experiments in P.
      pacificus show significant differences in the effects of individual somatic
      tissues on germ line patterning in comparison to C. elegans.

PMID- 15572151
TI  - Excess biglycan causes eyelid malformation by perturbing muscle development and
      TGF-alpha signaling.
AB  - Tissue morphogenesis during development is regulated by growth factors and
      cytokines, and is characterized by constant remodeling of extracellular matrix
      (ECM) in response to signaling molecules, for example, growth factors, cytokines,
      and so forth. Proteoglycans that bind growth factors are potential regulators of
      tissue morphogenesis during embryonic development. In this study, we showed that
      transgenic mice overexpressing biglycan under the keratocan promoter exhibited
      exposure keratitis and premature eye opening from noninfectious eyelid ulceration
      due to perturbation of eyelid muscle formation and the failure of meibomian gland
      formation. In addition, in vitro analysis revealed that biglycan binds to TGF
      alpha, thus interrupting EGFR signaling pathways essential for mesenchymal cell
      migration induced by eyelid epithelium. The defects of TGF-alpha signaling by
      excess biglycan were further augmented by the interruption of the autocrine or
      paracrine loop of the EGFR signaling pathway of HB-EGF expression elicited by TGF
      alpha. These results are consistent with the notion that under physiological
      conditions, biglycan secreted by mesenchymal cells serves as a regulatory
      molecule for the formation of a TGF-alpha gradient serving as a morphogen of
      eyelid morphogenesis.

PMID- 15572152
TI  - Characterization of expanded intermediate cell mass in zebrafish chordin morphant
      embryos.
AB  - We investigated the mechanisms of intermediate cell mass (ICM) expansion in
      zebrafish chordin (Chd) morphant embryos and examined the role of BMPs in
      relation to this phenotype. At 24 h post-fertilization (hpf), the expanded ICM of
      embryos injected with chd morpholino (MO) (ChdMO embryos) contained a monotonous
      population of hematopoietic progenitors. In situ hybridization showed that
      hematopoietic transcription factors were ubiquitously expressed in the ICM
      whereas vascular gene expression was confined to the periphery. BMP4 (but not
      BMP2b or 7) and smad5 mRNA were ectopically expressed in the ChdMO ICM. At 48
      hpf, monocytic cells were evident in both the ICM and circulation of ChdMO but
      not WT embryos. While injection of BMP4 MO had no effect on WT hematopoiesis, co
      injecting BMP4 with chd MOs significantly reduced ICM expansion. Microarray
      studies revealed a number of genes that were differentially expressed in ChdMO
      and WT embryos and their roles in hematopoiesis has yet to be determined. In
      conclusion, the expanded ICM in ChdMO embryos represented an expansion of
      embryonic hematopoiesis that was skewed towards a monocytic lineage. BMP4, but
      not BMP2b or 7, was involved in this process. The results provide ground for
      further research into the mechanisms of embryonic hematopoietic cell expansion.

PMID- 15572153
TI  - Distinctive functions of membrane type 1 matrix-metalloprotease (MT1-MMP or MMP
      14) in lung and submandibular gland development are independent of its role in
      pro-MMP-2 activation.
AB  - Membrane type 1-matrix metalloprotease (MT1-MMP or MMP-14) is a major activator
      of pro-MMP-2 and is essential for skeletal development. We show here that it is
      required for branching morphogenesis of the submandibular gland but not the lung.
      Instead, in the lung, it is essential for postnatal development of alveolar
      septae. Lung development in Mmp14-/- mice is arrested at the prealveolar stage
      with compensatory hyperinflation of immature saccules. Mmp2-/- mice lacked
      comparable defects in the lung and submandibular gland, suggesting that MT1-MMP
      acts via mechanisms independent of pro-MMP-2 activation. Since the developmental
      defects in the lung are first manifest around the time of initial vascularization
      (E16.5), we investigated the behavior of pulmonary endothelial cells from
      Mmp14+/+ and Mmp14-/- mice. Endothelial cells from lungs of 1-week-old Mmp14-/-
      mice show reduced migration and formation of three-dimensional structures on
      Matrigel. Since pulmonary septal development requires capillary growth, the
      underlying mechanism of pulmonary hypoplasia in Mmp14-/- mice may be defective
      angiogenesis, supporting a model in which angiogenesis is a critical rate
      limiting step for acquisition of pulmonary parenchymal mass.

PMID- 15572154
TI  - New strategies for structure-guided design of AIDS antivirals.

PMID- 15572155
TI  - Adaptive inhibitors of the HIV-1 protease.
AB  - A significant obstacle to the efficacy of drugs directed against viral targets is
      the presence of amino acid polymorphisms in the targeted molecules. Amino acid
      polymorphisms may occur naturally due to the existence of variations within and
      between viral strains or as the result of mutations associated with drug
      resistance. An ideal drug will be one that is extremely effective against a
      primary target and maintains its effectiveness against the most important
      variations of the target molecule. A drug that simultaneously inhibits different
      variants of the target will lead to a faster suppression of the virus, retard the
      appearance of drug-resistant mutants and provide more efficacious and, in the
      long range, more affordable therapies. Drug molecules with the ability to inhibit
      several variants of a target with high affinity have been termed adaptive drugs
      (Nat. Biotechnol. 20 (2002) 15; Biochemistry 42 (2003) 8459; J. Cell. Biochem.
      S37 (2001) 82). Current drug design paradigms are predicated upon the lock-and
      key hypothesis, which emphasizes shape complementarity as a way to attain
      specificity and improved binding affinity. Shape complementarity is accomplished
      by the introduction of conformational constraints in the drug molecule. While
      highly constrained molecules do well against a unique target, they lack the
      ability to adapt to target variations like those originating from naturally
      occurring polymorphisms or drug-resistant mutations. Targeting an array of
      closely related targets rather than a single one while still maintaining
      selectivity, requires a different approach. A plausible strategy for designing
      high affinity adaptive inhibitors is to engineer their most critical interactions
      (for affinity and specificity) with conserved regions of the target while
      allowing for adaptability through the introduction of flexible asymmetric
      functionalities in places facing variable regions of the target. The fundamental
      thermodynamics and structural principles associated with this approach are
      discussed in this chapter.

PMID- 15572156
TI  - Crystallography and the design of anti-AIDS drugs: conformational flexibility and
      positional adaptability are important in the design of non-nucleoside HIV-1
      reverse transcriptase inhibitors.
AB  - Drug resistance is a key cause of failure for treatment of HIV infection. The
      efficacy of non-nucleoside reverse transcriptase inhibiting (NNRTI) drugs is
      impaired by rapid emergence of drug-resistance mutations. A multidisciplinary
      effort led to the discovery of the potent NNRTIs dapivirine and etravirine, both
      of which are diarylpyrimidine (DAPY) derivatives. Systematic structural and
      molecular modeling studies of HIV-1 reverse transcriptase (RT)/NNRTI complexes
      revealed different modes of inhibitor binding, and some of the DAPY inhibitors
      can bind to RT in different conformations. The torsional flexibility ("wiggling")
      of the inhibitors can generate numerous conformational variants and the
      compactness of the inhibitors permits significant repositioning and reorientation
      (translation and rotation) within the pocket ("jiggling"). Such adaptations
      appear to be critical for the ability of the diarylpyrimidine NNRTIs to retain
      their potency against a wide range of drug-resistant HIV-1 RTs. Exploitation of
      inhibitor conformational flexibility (such as torsional flexibility about
      strategically located chemical bonds) can be a powerful element of drug design,
      especially for the design of drugs that will be effective against rapidly
      mutating targets (which is a collection of related targets).

PMID- 15572157
TI  - Proteins that bind high-mannose sugars of the HIV envelope.
AB  - A broad range of proteins bind high-mannose carbohydrates found on the surface of
      the envelope protein gp120 of the human immunodeficiency virus and thus interfere
      with the viral life cycle, providing a potential new way of controlling HIV
      infection. These proteins interact with the carbohydrate moieties in different
      ways. A group of them interacts as typical C-type lectins via a Ca2+ ion. Another
      group interacts with specific single, terminal sugars, without the help of a
      metal cation. A third group is involved in more intimate interactions, with
      multiple carbohydrate rings and no metal ion. Finally, there is a group of
      lectins for which the interaction mode has not yet been elucidated. This review
      summarizes, principally from a structural point of view, the current state of
      knowledge about these high-mannose binding proteins and their mode of sugar
      binding.

PMID- 15572158
TI  - Chemical and electrical synapses: recent progress. Proceedings of an
      international workshop. October 15-23, 2001. Santiago, Chile.

PMID- 15572159
TI  - A review on electron microscopy and neurotransmitter systems.
AB  - The purpose of this article is to review the contributions of transmission
      electron microscopy studies to the understanding of brain circuits and
      neurotransmitter systems. Our views on the microstructure of connections between
      neurons have gradually changed, and now we recognize that the classical mental
      image we had on a chemical synapse is no longer applicable to every neuronal
      connection. We highlight studies that converge to point out that, while the most
      prevalent fast transmitters in the brain, glutamate and GABA, are stored in
      small, clear synaptic vesicles (SSV) and released at synapses, neuropeptides are
      exclusively stored in large dense core vesicles (LDCV) and released
      extrasynaptically. Amine transmitters are preferentially, but not exclusively,
      accumulated in LDCV and may be released at synaptic or extrasynaptic sites. We
      discuss evidence suggesting that axon terminals from pyramidal cortical neurons
      and dorsal thalamic neurons lack LDCV and therefore could not use neuropeptides
      as transmitters. This idea fits with the fast, high temporal resolution
      information processing that characterizes cortical and thalamic function.

PMID- 15572160
TI  - Synaptic vesicle pools and plasticity of synaptic transmission at the Drosophila
      synapse.
AB  - Our knowledge on the Drosophila neuromuscular synapse is rapidly expanding. Thus,
      this synapse offers an excellent model for studies of the molecular mechanism of
      synaptic transmission and synaptic plasticity. Two synaptic vesicle (SV) pools
      have been identified and characterized using a fluorescent styryl dye, FM1-43, to
      stain SVs. They are termed the exo/endo cycling pool (ECP), which corresponds to
      the readily releasable pool (RRP) defined electrophysiologically, and the reserve
      pool (RP). These two pools were identified first in a temperature-sensitive
      paralytic mutant, shibire, and subsequently confirmed in wild-type larvae. The
      ECP participates in synaptic transmission during low frequency firing of
      presynaptic nerves and locates in the periphery of presynaptic boutons in the
      vicinity of release sites, while SVs in the RP spread toward the center of
      boutons and are recruited only during tetanic stimulation. These two pools are
      separately replenished by endocytosis. Cyclic AMP facilitates recruitment of SVs
      from the RP to the ECP. Activation of presynaptic metabotropic glutamate
      receptors recruits SVs from the RP and enhances SV release by elevation of the
      cAMP level. Memory mutants that have defects in the cAMP/PKA cascade, dunce and
      rutabaga, exhibit reduced levels of recruitment of synaptic SVs from the RP to
      the ECP and have limited short-term synaptic plasticity. SV mobilization between
      the two pools could be a key step for changes in synaptic efficacy. Since a
      variety of mutants that have distinct defects in synaptic transmission are
      available for detailed studies of synaptic function, this direction of approach
      in Drosophila seems promising.

PMID- 15572161
TI  - Changes on the properties of glycine receptors during neuronal development.
AB  - Glycine receptors (GlyRs) play a major role in the excitability of spinal cord
      and brain stem neurons. During development, several properties of these receptors
      undergo significant changes resulting in major modifications of their
      physiological functions. For example, the receptor structure switches from a
      monomeric alpha or heteromeric alpha 2 beta in immature neurons to an alpha 1
      beta receptor type in mature neurons. Together with these changes in receptor
      subunits, the postsynaptic cluster size increases with development. Parallel to
      these modifications, the apparent receptor affinity to glycine and strychnine, as
      well as that of Zn(2+) and ethanol increases with time. The mature receptor is
      characterized by a slow desensitizing current and high sensitivity to modulation
      by protein kinase C. Also, the high level of glycinergic transmission in immature
      spinal neurons modulates neuronal excitability causing membrane depolarization
      and changes in intracellular calcium. Due to these properties, chronic inhibition
      of glycinergic transmission affects neurite outgrowth and produces changes in the
      level of synaptic transmission induced by GABA(A) and AMPA receptors. Finally,
      the high level of plasticity found in immature GlyRs is likely associated to
      changes in cytoskeleton dynamics.

PMID- 15572162
TI  - Neurotransmission in the carotid body: transmitters and modulators between glomus
      cells and petrosal ganglion nerve terminals.
AB  - The carotid body (CB) is the main arterial chemoreceptor. The most accepted model
      of arterial chemoreception postulates that carotid body glomus (type I) cells are
      the primary receptors, which are synaptically connected to the nerve terminals of
      petrosal ganglion (PG) neurons. In response to natural stimuli, glomus cells are
      expected to release one (or more) transmitter(s) which, acting on the peripheral
      nerve terminals of processes from chemosensory petrosal neurons, increases the
      sensory discharge. Among several molecules present in glomus cells, acetylcholine
      and adenosine nucleotides and dopamine are considered as excitatory transmitter
      candidates. In this review, we will examine recent evidence supporting the notion
      that acetylcholine and adenosine 5'-triphosphate are the main excitatory
      transmitters in the cat and rat carotid bodies. On the other hand, dopamine may
      act as a modulator of the chemoreception process in the cat, but as an excitatory
      transmitter in the rabbit carotid body.

PMID- 15572163
TI  - Electrophysiology and plasticity in isolated postsynaptic densities.
AB  - The organization and regulation of excitatory synapses in the mammalian CNS
      entails complex molecular and cellular processes. In the postsynaptic membrane,
      scaffolding proteins bring together glutamate receptors with multiple regulatory
      proteins involved in signal transduction. This gives rise to an elaborate
      postsynaptic structure known as the postsynaptic density (PSD). This protein
      network plays a critical role in the regulation of glutamate receptor function
      and thus in synaptic plasticity. To study this regulation, we have developed a
      system in which ionotropic glutamate receptors (iGluRs) can be recorded, in the
      steady state, by the patch clamp technique in isolated PSDs incorporated into
      giant liposomes. In this preparation, ionotropic glutamate receptors maintain
      their characteristic physiological and pharmacological properties. The recordings
      reflect the presence of channel clusters, as multiple conductance and
      subconductance states are observed. Each of the receptor subtypes is activated by
      a specific set of kinases that are activated differentially by Ca(2+): the
      "kainate receptor kinases" are active even in the presence of EGTA, i.e. they are
      not calcium-dependent; the "N-methyl-D-aspartate receptor (NMDAR) channel
      kinases" are active in the presence of submicromolar calcium concentrations,
      whereas the "alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA)
      receptor kinases" need microM calcium for activation. The NMDA receptor showed
      its characteristic voltage-dependent Mg(2+) blockade, and activation by
      phosphorylation was in part a consequence of a relief of Mg(2+) blockade. These
      results allow us to propose a model in which phosphorylation of NMDA receptors
      can contribute to a long-lasting and self-maintained change in synaptic function.
      The experimental approach we present will allow us to test the functional
      consequence of activation of the multiple signal transduction pathways thought to
      regulate excitatory neurotransmission in the adult CNS.

PMID- 15572164
TI  - Structural basis for lipid modulation of nicotinic acetylcholine receptor
      function.
AB  - The nicotinic acetylcholine receptor (AChR) is the archetype molecule in the
      superfamily of ligand-gated ion channels (LGIC). Members of this superfamily
      mediate fast intercellular communication in response to endogenous
      neurotransmitters. This review is focused on the structural and functional
      crosstalk between the AChR and lipids in the membrane microenvironment, and the
      modulation exerted by the latter on ligand binding and ion translocation.
      Experimental approaches using Laurdan extrinsic fluorescence and Forster-type
      resonance energy transfer (FRET) that led to the characterization of the polarity
      and molecular dynamics of the liquid-ordered phase AChR-vicinal lipids and the
      bulk membrane lipids, and the asymmetry of the AChR-rich membrane are reviewed
      first. The topological relationship between protein and lipid moieties and the
      changes in physical properties induced by exogenous lipids are discussed next.
      This background information lays the basis for understanding the occurrence of
      lipid sites in the AChR transmembrane region, and the selectivity of the protein
      lipid interactions. Changes in FRET efficiency induced by fatty acids,
      phospholipid and cholesterol (Chol), led to the identification of discrete sites
      for these lipids on the AChR protein, and electron-spin resonance (ESR)
      spectroscopy has recently facilitated determination of the stoichiometry and
      selectivity for the AChR of the shell lipid. The influence of lipids on AChR
      function is discussed next. Combined single-channel and site-directed mutagenesis
      data fostered the recognition of lipid-sensitive residues in the transmembrane
      region, dissecting their contribution to ligand binding and channel gating,
      opening and closing. Experimental evidence supports the notion that the interface
      between the protein moiety and the adjacent lipid shell is the locus of a variety
      of pharmacologically relevant processes, including the action of steroids and
      other lipids.

PMID- 15572165
TI  - Structural and functional organization of synaptic acetylcholinesterase.
AB  - The expression of the synaptic asymmetric form of the enzyme acetylcholinesterase
      (AChE) depends of two different genes: the gene that encodes for the catalytic
      subunit and the gene that encodes for the collagenic tail, ColQ. Asymmetric AChE
      is specifically localized to the basal lamina at the neuromuscular junction
      (NMJ). This highly organized distribution pattern suggests the existence of one
      or more specific binding sites in ColQ required for its anchorage to the synaptic
      basal lamina. Recent evidence support this notion: first, the presence of two
      heparin-binding domains in ColQ that interact with heparan sulfate proteoglycans
      (HSPGs) at the synaptic basal lamina; and second, a knockout mouse for perlecan,
      a HSPG concentrated in nerve-muscle contact, in which absence of asymmetric AChE
      at the NMJ is observed. The physiological importance of collagen-tailed AChE form
      in skeletal muscle has been illustrated by the identification of several
      mutations in the ColQ gene. These mutations determine end-plate
      acetylcholinesterase deficiency and induce one type of synaptic functional
      disorders observed in Congenital Myasthenic Syndromes (CMSs).

PMID- 15572166
TI  - PDZ-containing proteins: alternative splicing as a source of functional
      diversity.
AB  - Scaffold proteins allow specific protein complexes to be assembled in particular
      regions of the cell at which they organize subcellular structures and signal
      transduction complexes. This characteristic is especially important for neurons,
      which are highly polarized cells. Among the domains contained by scaffold
      proteins, the PSD-95, Discs-large, ZO-1 (PDZ) domains are of particular relevance
      in signal transduction processes and maintenance of neuronal and epithelial
      polarity. These domains are specialized in the binding of the carboxyl termini of
      proteins allowing membrane proteins to be localized by the anchoring to the
      cytoskeleton mediated by PDZ-containing scaffold proteins. In vivo studies
      carried out in Drosophila have taught that the role of many scaffold proteins is
      not limited to a single process; thus, in many cases the same genes are expressed
      in different tissues and participate in apparently very diverse processes. In
      addition to the differential expression of interactors of scaffold proteins, the
      expression of variants of these molecular scaffolds as the result of the
      alternative processing of the genes that encode them is proving to be a very
      important source of variability and complexity on a main theme. Alternative
      splicing in the nervous system is well documented, where specific isoforms play
      roles in neurotransmission, ion channel function, neuronal cell recognition, and
      are developmentally regulated making it a major mechanism of functional
      diversity. Here we review the current state of knowledge about the diversity and
      the known function of PDZ-containing proteins in Drosophila with emphasis in the
      role played by alternatively processed forms in the diversity of functions
      attributed to this family of proteins.

PMID- 15572167
TI  - Corticotropin-releasing hormone and urocortin: redundant or distinctive
      functions?
AB  - Neuropeptides play important roles in synaptic transmission. Among them, the
      peptides of the corticotropin-releasing hormone (CRH) family present interesting
      features. The two main mammalian peptides of this family, CRH and urocortin
      (UCN), signal through the same receptors, CRH-R1 and CRH-R2. The question arises
      as to whether these peptides have redundant or distinctive functions. The fact
      that CRH and UCN have high affinity for both receptors has hampered the
      possibility to define the functional contribution of each peptide. Recent studies
      conducted on mice deficient in CRH, CRH-R1, CRH-R2 and CRH-R1/CRH-R2, as well as
      in two different UCN-deficient mice, have added relevant information towards the
      understanding of the role of this peptide family in the CNS. Our new anatomical
      evidence of UCN expression in the septum will be discussed in this context.

PMID- 15572168
TI  - Functional interactions between somatodendritic dopamine release, glutamate
      receptors and brain-derived neurotrophic factor expression in mesencephalic
      structures of the brain.
AB  - Dopaminergic nigrostriatal neurons may be considered as bipolar functional
      entities since they are endowed with the ability to synthesize, store and release
      the transmitter dopamine (DA) at the somatodendritic level in the substantia
      nigra (SN). Such dendritic DA release seems to be distinct from the transmitter
      release occurring at the axon terminal and seems to rely preferentially on volume
      transmission to exert its physiological effects. An increased glutamatergic
      (Gluergic) transmission into the SN facilitates such dendritic DA release via
      activation of NMDA-receptors (NMDA-Rs) and to a lesser extent through group II
      metabotropic glutamate receptors (mGluRs). In addition, nigral mGluRs
      functionally interact with NMDA-Rs in the SN, further modulating the NMDA-R
      mediated increase of DA release from dendrites in the SN. In turn, dendritically
      released DA may exert, via D1 receptors, a tonic inhibitory control upon nigral
      glutamate (Glu). Furthermore, released DA, via D2/D3 autoreceptors, produces an
      autoinhibitory effect upon DA cell firing and its own release process. An
      increased Gluergic transmission into the SN may also induce, via activation of
      NMDA-Rs, an augmented expression of different brain-derived neurotrophic factor
      (BDNF) gene transcripts in this brain area. Pharmacological evidence suggests
      that non-NMDA-Rs could also participate in the regulation of BDNF gene expression
      in the SN. Glu-mediated changes of nigral BDNF expression could regulate, in
      turn, the expression of important transmitter-related proteins in the SN, such as
      different NMDA-R subunits, mGluRs and DA-D3 receptors. In conclusion, Glu-DA-BDNF
      interactions in the SN may play an important role in modulating the flow of
      neuronal information in this brain structure under normal conditions, as well as
      during adaptive and plastic responses associated with various neurological and
      psychiatric disorders.

PMID- 15572169
TI  - Role of noradrenergic projections to the bed nucleus of the stria terminalis in
      the regulation of the hypothalamic-pituitary-adrenal axis.
AB  - The bed nucleus of the stria terminalis (BNST) plays an important role in the
      regulation of the hypothalamic-pituitary-adrenal (HPA) axis during stress and it
      is a major extrahypothalamic relay to the paraventricular nucleus of the
      hypothalamus (PVN) from the amygdala and the hippocampus. In this review, we
      discuss the anatomical, neurochemical and behavioral evidence that substantiate a
      role for noradrenergic terminals of the anterior BNST in the regulation of the
      HPA axis. We propose the hypothesis that BNST noradrenaline (NA) participates in
      the regulation of the hippocampal inhibitory influence on the HPA axis
      activation. The observation that NA exerts a tonic inhibitory effect upon
      glutamatergic transmission in the anterior BNST supports this hypothesis. We also
      discuss the known mechanisms involved in the regulation of BNST NA extracellular
      levels and the possible interactions between NA and corticotropin-releasing
      hormone (CRH), and of CRH with glutamate (GLU) in the regulation of the HPA axis
      activity exerted by the BNST. The evidence discussed in the present review
      situates the BNST as a key extrahypothalamic center that relays and integrates
      limbic and autonomic information related to stress responses suggesting that
      dysregulation in the functioning of the BNST may underlie the pathophysiology of
      stress-related psychiatric disorders.

PMID- 15572170
TI  - CNTF, a pleiotropic cytokine: emphasis on its myotrophic role.
AB  - Ciliary neurotrophic factor (CNTF) is a cytokine whose neurotrophic and
      differentiating effects over cells in the central nervous system (CNS) have been
      clearly demonstrated. This article summarizes the general characteristics of
      CNTF, its receptor and the signaling pathway that it activates and focuses on its
      effects over skeletal muscle, one of its major target tissues outside the central
      nervous system. The evidence for the existence of other molecules that signal
      through the same complex as CNTF is also reviewed.

PMID- 15572171
TI  - The formation of skeletal muscle myotubes requires functional membrane receptors
      activated by extracellular ATP.
AB  - Skeletal muscle differentiation follows an organized sequence of events including
      commitment, cell cycle withdrawal, and cell fusion to form multinucleated
      myotubes. The role of adenosine 5'-triphosphate (ATP)-mediated signaling in
      differentiation of skeletal muscle myoblasts was evaluated in C(2)C(12) cells, a
      myoblast cell line. Cell differentiation was inhibited by P2X receptor blockers
      or by degradation of endogenous ATP with apyrase. However, pertussis toxin, known
      to block only a group of P2Y receptors, did not alter the differentiation
      process. Cells were heterogeneous in their expression of functional P2X
      receptors, evaluated by the uptake of fluorescent permeability tracers (Lucifer
      yellow and ethidium bromide), and by immunofluorescence of P2X(7) receptors.
      Moreover, xestospongin C, a selective and membrane-permeable inhibitor of IP(3)
      receptors, inhibited both myotube formation and myogenin expression. Based on
      these results, we suggest that the known increase in intracellular Ca(2+)
      concentration required for differentiation is due at least in part to Ca(2+)
      influx through P2X receptors and Ca(2+) release from intracellular stores. The
      possible involvement of P2X receptors and other pathways that might set the
      intracellular Ca(2+) at the level required for myoblast differentiation as well
      as the possible involvement of gap junction channels in the intercellular
      transfer of second messengers involved in coordinating myogenesis is proposed.

PMID- 15572172
TI  - Update on connexins and gap junctions in neurons and glia in the mammalian
      nervous system.
AB  - Among the 20 proposed members of the connexin family of proteins that form gap
      junctional intercellular communication (GJIC) channels in mammalian tissues, over
      half are reported to be expressed in the nervous system. There have been
      conflicting observations, however, concerning the particular connexins expressed
      by astrocytes, oligodendrocytes, Schwann cells and neurons. Identification of the
      several connexin proteins at gap junctions between each neuronal and glial cell
      type is essential for the rational design of investigations into the functions of
      GJIC between glial cells and into the functional contributions of electrical and
      "mixed" (chemical plus electrical) synapses to communication between neurons in
      the mammalian nervous system. In this report, we provide a summary of recent
      findings regarding the localization of connexins in gap junctions between glial
      cells and between neurons. Attention is drawn to technical considerations
      involved in connexin localization by light and electron microscope
      immunohistochemistry and to limitations of physiological methods and approaches
      currently used to analyze neuronal and glial coupling. Early physiological
      studies that provided evidence for the presence of gap junctions and electrical
      synapses in isolated regions of the mammalian brain and spinal cord are
      reexamined in light of recent evidence for widely expressed neuron-specific
      connexins and for the existence of several newly discovered types of gap
      junctions linking neurons.

PMID- 15572173
TI  - Gap junctions in developing neocortex: a review.
AB  - Several independent lines of evidence indicate that gap junctional coupling is
      widespread and functionally important in early cortical development. The
      extensive expression of many connexins, the clusters of coupled neuroblasts or
      neurons revealed by tracer injections or the functional coactivation of neurons
      shown by calcium imaging can be seen as pieces of the same puzzle. At the same
      time, there is a lack of electrophysiological experiments at early developmental
      stages that directly demonstrate coupling between pairs of cells. The function of
      this gap junctional coupling is still mysterious, though it may be involved in
      controlling neurogenesis, differentiation or the formation of columnar
      microcircuits.

PMID- 15572174
TI  - Dynamics of electrical transmission at club endings on the Mauthner cells.
AB  - Identifiable mixed electrical and chemical synapses on Mauthner cells, the club
      endings, have historically provided a window for the study of electrical
      transmission in vertebrates because of their accessibility for both physiological
      and ultrastructural characterization. Recent data show that electrical
      transmission at these terminals is mediated by connexin35 (Cx35), the fish
      ortholog of the mammalian neuronal gap junction protein, connexin36 (Cx36). While
      electrical synapses are still perceived by many as passive intercellular channels
      that lack modifiability, a wealth of experimental evidence shows that electrical
      synapses at club endings are very plastic and subject to dynamic regulatory
      control by several mechanisms. The widespread distribution of connexin35 and
      connexin36 and the ubiquity of some of the proposed regulatory elements suggest
      that other electrical synapses may be similarly regulated.

PMID- 15572175
TI  - New insights into the expression and function of neural connexins with transgenic
      mouse mutants.
AB  - Gap junctions represent direct intercellular conduits between contacting cells.
      The subunit proteins of these conduits are called connexins. To date, 20 and 21
      connexin genes have been described in the mouse and human genome, respectively,
      many of them represent sequence-orthologous pairs. Targeted deletion of connexin
      genes in the mouse genome opened new insights into the biological function of
      these channel forming proteins, which, in some cases, could be correlated to
      phenotypic abnormalities in humans, suffering from inherited diseases caused by
      mutations in the corresponding orthologous connexin gene. Replacing the connexin
      coding DNA by an appropriate reporter gene has clarified in several cases its
      cell type specific expression in mouse brain. Various studies demonstrated that
      connexin36 is mainly expressed in interneurons of retina and brain. Targeted
      deletion of connexin36 evoked a loss of electrical signal transduction and
      interferes with synchrony which probably leads to defects in visual transmission
      and memory. Deletion of connexin43 in astrocytes of mouse brain resulted in
      increased spreading depression consistent with the notion of altered "spatial
      buffering" of K(+) ions and glutamate secreted by active neurons. General
      connexin30-deficiency led to hearing impairment and apoptosis of hair cells,
      similar to that observed in mice with cochlea specific deletion of connexin26.
      Reporter gene expression in connexin30-deficient mice indicated that astrocytes
      in certain brain regions and leptomeningeal as well as ependymal cells are
      labelled. Reporter gene expression in connexin45- and connexin47-deficient mice
      was used to reassign connexin45 expression to certain CNS neurons and connexin47
      expression to oligodendrocytes.

PMID- 15572176
TI  - A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis.
AB  - A strong glial reaction typically surrounds the affected upper and lower motor
      neurons and degenerating descending tracts of ALS patients. Reactive astrocytes
      in ALS contain protein inclusions, express inflammatory makers such as the
      inducible forms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2),
      display nitrotyrosine immunoreactivity and downregulate the glutamate transporter
      EAAT2. In this review, we discuss the evidence sustaining an active role for
      astrocytes in the induction and propagation of motor neuron loss in ALS.
      Available evidence supports the view that glial activation could be initiated by
      proinflammatory mediators secreted by motor neurons in response to injury,
      axotomy or muscular pathology. In turn, reactive astrocytes produce nitric oxide
      and peroxynitrite, which cause mitochondrial damage in cultured neurons and
      trigger apoptosis in motor neurons. Astrocytes may also contribute to the
      excitotoxic damage of motor neurons by decreasing glutamate transport or actively
      releasing the excitotoxic amino acid. In addition, reactive astrocytes secrete
      pro-apoptotic mediators, such as nerve growth factor (NGF) or Fas-ligand, a
      mechanism that may serve to eliminate vulnerable motor neurons. The comprehensive
      understanding of the interactions between motor neurons and glia in ALS may lead
      to a more accurate theory of the pathogenesis of the disease.

PMID- 15572177
TI  - Signal transduction during amyloid-beta-peptide neurotoxicity: role in Alzheimer
      disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with progressive
      dementia accompanied by two main structural changes in the brain: intracellular
      protein deposits termed neurofibrillary tangles (NFT) and extracellular amyloid
      protein deposits surrounded by dystrophic neurites that constitutes the senile
      plaques. Currently, it is widely accepted that amyloid beta-peptide (A beta)
      metabolism disbalance is crucial for AD progression. A beta deposition may be
      enhanced by molecular chaperones, including metals like copper and proteins like
      acetylcholinesterase (AChE). At the neuronal level, several AD-related proteins
      interact with transducers of the Wnt/beta-catenin signaling pathway, including
      beta-catenin and glycogen synthase kinase 3 beta (GSK-3 beta) and both in vitro
      and in vivo studies suggest that Wnt/beta-catenin signaling is a target for A
      beta toxicity. Accordingly, activation of this signaling by lithium or Wnt
      ligands in AD-experimental animal models or in primary hippocampal neurons
      attenuate A beta neurotoxicity by recovering beta-catenin levels and Wnt-target
      gene expression of survival genes such as bcl-2. On the other hand, peroxisomal
      proliferator-activated receptor gamma (PPAR gamma) and muscarinic acetylcholine
      receptor (mAChR) agonists also activate Wnt/beta-catenin signaling and they have
      neuroprotective effects on hippocampal neurons. Our studies are consistent with
      the idea that a sustained loss of function of Wnt signaling components would
      trigger a series of events, determining the onset and development of AD and that
      modulation of this pathway through the activation of cross-talking signaling
      cascades should be considered as a possible therapeutic strategy for AD
      treatment.

PMID- 15572179
TI  - Effects of dexamethasone on declarative memory function in posttraumatic stress
      disorder.
AB  - Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal
      based memory have been associated with posttraumatic stress disorder (PTSD), and
      the administration of exogenous glucocorticoids has been shown to result in a
      transient verbal declarative memory impairment in healthy human subjects. The
      purpose of this study was to assess the effects of the glucocorticoid
      dexamethasone on verbal declarative memory function in patients with PTSD. Forty
      two men and women with (n=14) and without (n=28) PTSD received placebo or
      dexamethasone (1 and 2 mg on two successive days) in a double-blind, randomized
      fashion. Declarative memory was assessed with paragraph recall at baseline (day
      1) and day 3. There was a significant interaction between diagnosis and drug
      (dexamethasone vs. placebo) on paragraph recall related to a relative detrimental
      effect of dexamethasone on memory function in healthy subjects, but not those
      with PTSD. These findings are consistent with an altered sensitivity of
      declarative memory function in PTSD to regulation by glucocorticoids, possibly
      explainable by alterations in glucocorticoid receptors in the hippocampus or
      other brain regions mediating declarative memory.

PMID- 15572180
TI  - Serotonergic function in the central nervous system is associated with daily
      ratings of positive mood.
AB  - Serotonin constrains a broad array of animal and human behavior and may also
      inhibit the expression of mood or affective states among humans. For the most
      part, this research has focused on the association of central serotonergic
      function with negative affectivity (i.e., anxiety, depression, hostility), with
      less attention on the relationship between serotonergic function and positive
      affect or mood. The current study was conducted to examine the relationship
      between a measure of central serotonergic activity and daily ratings of positive
      and negative mood in a nonpatient sample. Two hundred and fifty-four adults, aged
      24-60, completed end-of-day ratings of positive and negative mood items over 7
      consecutive days. A neuropharmacological challenge was administered to index
      central serotonergic function, i.e., the maximal prolactin (PRL) response to
      fenfluramine, a serotonin releasing agent. Hierarchical linear regression
      analyses indicated that the peak PRL response to fenfluramine was positively
      associated with positive mood, averaged over 7 days, after controlling for known
      predictors of the PRL response. This relationship remained significant after
      controlling for average negative mood, for the presence of a current DSM-III-R
      diagnosis, and for trait measures of Neuroticism and Extraversion. In contrast,
      the PRL response to fenfluramine was not associated with average negative mood,
      although it was inversely correlated with trait negative affectivity (i.e.,
      Neuroticism). These results suggest that deficiencies in serotonergic function
      may reflect the relative absence of positive mood.

PMID- 15572178
TI  - Role of connexin-based gap junction channels and hemichannels in ischemia-induced
      cell death in nervous tissue.
AB  - Gap junction channels and hemichannels formed of connexin subunits are found in
      most cell types in vertebrates. Gap junctions connect cells via channels not open
      to the extracellular space and permit the passage of ions and molecules of
      approximately 1 kDa. Single connexin hemichannels, which are connexin hexamers,
      are present in the surface membrane before docking with a hemichannel in an
      apposed membrane. Because of their high conductance and permeability in cell-cell
      channels, it had been thought that connexin hemichannels remained closed until
      docking to form a cell-cell channel. Now it is clear that at least some
      hemichannels can open to allow passage of molecules between the cytoplasm and
      extracellular space. Here we review evidence that gap junction channels may allow
      intercellular diffusion of necrotic or apoptotic signals, but may also allow
      diffusion of ions and substances from healthy to injured cells, thereby
      contributing to cell survival. Moreover, opening of gap junction hemichannels may
      exacerbate cell injury or mediate paracrine or autocrine signaling. In addition
      to the cell specific features of an ischemic insult, propagation of cell damage
      and death within affected tissues may be affected by expression and regulation of
      gap junction channels and hemichannels formed by connexins.

PMID- 15572181
TI  - High sensitivity to punishment and low impulsivity in obsessive-compulsive
      patients with hoarding symptoms.
AB  - Recent factor-analytic studies involving over 2000 patients have reduced the
      symptoms of obsessive-compulsive disorder (OCD) into a few dimensions or
      potentially overlapping syndromes. Hoarding consistently emerged as a separate
      factor in all these studies. This study investigated the relationship between OCD
      symptom dimensions and normal personality traits in a sample of 56 OCD patients.
      They were administered the Sensitivity to Punishment and Sensitivity to Reward
      Questionnaire and the Eysenck Personality Questionnaire, derived from Gray's and
      Eysenck's personality models, respectively. The personality scores were
      correlated with previously identified symptom dimensions from the Yale-Brown
      Obsessive-Compulsive Scale Symptom Checklist (Y-BOCS-SC), controlling for overall
      illness severity. High scores on the hoarding dimension of the Y-BOCS-SC were
      positively correlated with scores on the Sensitivity to Punishment scale and
      negatively with Eysenck's Psychoticism scale. While high sensitivity to
      punishment is a personality feature common to many OCD patients, it is more
      strongly pronounced in patients with hoarding symptoms. These patients also
      appear to be less impulsive or novelty seeking as reflected by low scores on
      Eysenck's Psychoticism scale. High sensitivity to punishment and low novelty
      seeking in OCD hoarders might explain their poor compliance and response to
      conventional treatments, but this question needs to be explored further in a
      prospective treatment study.

PMID- 15572182
TI  - Association of aggressive behavior in Korean male schizophrenic patients with
      polymorphisms in the serotonin transporter promoter and catecholamine-O
      methyltransferase genes.
AB  - The incidence of aggressive behavior in patients with schizophrenia is higher
      than in the general population. Among particular gene polymorphisms posited to be
      involved in psychiatric disorders, the catecholamine-O-methyltransferase (COMT)
      and serotonin transporter (5-HTTPR) genes have been the focus of recent research
      on aggression. In this study, we hypothesized that both the COMT and the 5-HTTPR
      genotypes may be dependent on and related to aggression in Korean patients with
      schizophrenia. The subjects were 168 unrelated male schizophrenic patients
      diagnosed according to DSM-IV. Among two psychiatric hospital staff and medical
      university students, 158 unrelated male subjects with no lifetime history of
      psychiatric disorders were recruited to establish the COMT and 5-HTTPR genotype
      distribution in the general population. All episodes of aggression from the last
      discharge to readmission were rated. The Total Overt Aggression Scale (OAS) score
      (sum of the scores of all episodes of aggression), highest OAS score (highest
      individual episode score, 0-16), OAS category, and OAS category score (mean score
      within each category) were recorded. There were statistically significant effects
      of COMT genotype on the mean OAS 4 (physical aggression against other people)
      score and the highest OAS score. The most predictive was the OAS 4 score. There
      was a statistically significant effect of 5-HTTPR genotype on mean total score.
      Thus, the COMT gene is associated with the severity of aggression and with
      physical aggression against other people, whereas the 5-HTTPR gene is associated
      with the summary score of all episodes of aggression.

PMID- 15572183
TI  - Assessing publication bias in genetic association studies: evidence from a recent
      meta-analysis.
AB  - Publication bias may exist when nonsignificant findings remain unpublished,
      thereby artificially inflating the apparent magnitude of an effect. This concern
      is not new, but it is particularly current in relation to genetic association
      studies. Data from a recent meta-analysis of association studies of personality
      were used to assess the potential of different graphical and statistical methods
      for assessing evidence of publication bias. The results suggest that no single
      method is sufficient for assessing evidence of publication bias, and that such
      methods may also offer insight into potential sources of heterogeneity, which may
      in turn guide the design of future studies.

PMID- 15572184
TI  - Cognitive functioning in schizophrenia and bipolar disorder: comparison of
      performance on the Repeatable Battery for the Assessment of Neuropsychological
      Status.
AB  - Cognitive dysfunction is an important feature of schizophrenia and bipolar
      disorder. There is uncertainty about the relative magnitude of cognitive deficits
      in these disorders. We evaluated a total of 446 individuals: 229 with
      schizophrenia, 117 with bipolar disorder, and 100 controls without a history of
      psychiatric disorder. All participants were administered the Repeatable Battery
      for the Assessment of Neuropsychological Status (RBANS), a cognitive screening
      battery that evaluated immediate verbal memory, visuospatial/constructional
      abilities, attention, language, and delayed memory. A comparison of the three
      groups showed significant differences on the RBANS total score and all of the
      measured domains. In all of the comparisons, the schizophrenia group obtained the
      lowest scores, followed by the bipolar disorder group, and then the individuals
      without psychiatric disorder. In an analysis of covariance of RBANS total scores
      with the patient samples, the difference between schizophrenia and bipolar
      disorder remained significant after controlling for a range of demographic and
      clinical variables. Both schizophrenia and bipolar disorder are associated with
      significant cognitive impairments, but those in schizophrenia are more severe.
      Cognitive deficits may be an appropriate target of treatment interventions in
      these disorders.

PMID- 15572185
TI  - Intact figure-ground segmentation in schizophrenia.
AB  - As revealed by backward masking studies, schizophrenic patients show strong
      impairments of early visual processing. However, the underlying temporal
      mechanisms are not yet well understood. To shed light on the exact timing of
      these deficits, we employed a paradigm in which two masks follow each other. We
      investigated 16 medicated schizophrenic patients and a matched group of 14
      controls with a new backward masking technique, shine-through. In accordance with
      other masking studies, schizophrenic patients require a dramatically longer
      processing time to reach a predefined performance level compared with healthy
      subjects. However, patients are surprisingly sensitive to subtle differences in
      the timing of the two masks, revealing good temporal resolution. This good
      temporal resolution indicates intact and fast perceptual grouping and figure
      ground segmentation in spite of high susceptibility to masking procedures in
      schizophrenia.

PMID- 15572186
TI  - Is the biological nature of depressive symptoms in borderline patients without
      concomitant Axis I pathology idiosyncratic? Sleep EEG comparison with recurrent
      brief, major depression and control subjects.
AB  - The relationship between borderline personality disorder (BPD) and the affective
      disorders is controversial, and we have previously compared BPD and major
      depression (MD) with endocrinological measures and sleep electroencephalography
      (S-EEG). We have also compared BPD, MD and recurrent brief depression (RBD) using
      endocrine tests. We have proposed that depressive symptoms in BPD might have a
      biological substrate that is distinct from those in depressive illness without
      comorbid BPD. BPD has been proposed to overlap with RBD, which has been found to
      share perturbed biological substrates with MD, but we have not found the same
      biological pattern in BPD. When endocrinological data in BPD, MD and RBD were
      compared, we did not find evidence of biological linkage between BPD and RBD. To
      clarify the biological nature of depressive symptoms in BPD, we examined S-EEG
      characteristics in BPD, RBD, MD and controls. Among 20 BPD patients, 12 were also
      diagnosed as having clinical RBD. BPD patients showed differences in sleep
      continuity and especially in sleep architecture compared with RBD, MD and
      controls. BPD with or without clinical RBD did not show significant differences
      in any parameter. BPD with or without clinical RBD had less slow sleep activity
      not only than MD but also than non-borderline RBD patients. We propose that
      although BPD patients can have concomitant MD, they often exhibit a specific BPD
      associated affective syndrome that is different from both MD and non-borderline
      RBD in the quality and duration of symptoms and the biological substrate.

PMID- 15572187
TI  - A new look at inter-informant agreement on conduct disorder using a latent class
      approach.
AB  - This study examined agreement on aggressive and nonaggressive conduct disorder in
      a general population sample of 14- to 17-year-old adolescents (n=1165) and their
      mothers. We collected diagnostic interview data and applied latent class analyses
      to estimate inter-informant agreement. The preferred model for aggressive conduct
      disorder for both males and females was a one-latent-variable/two-class model
      specifying no inter-informant disagreement beyond chance expectations. This model
      estimated the prevalence of aggressive conduct disorder to be 13% for males and
      0.4% for females. For nonaggressive conduct disorder, a one-latent-variable/three
      class model specifying asymmetric agreement was preferred for both males and
      females. This model estimated the prevalence of nonaggressive conduct disorder in
      adolescents to be 18% according to males and 13% according to mothers. Prevalence
      estimates were 12% according to females and 7% according to mothers. Symptom
      sensitivity estimates for all models were poor whereas specificity estimates were
      near perfect to perfect. Males had higher rates of aggressive and nonaggressive
      conduct disorder across informants. There was a high level of adolescent-mother
      agreement on both types of conduct disorder. However, there were some
      differences, suggesting that aggressive and nonaggressive are two valid subtypes
      of conduct disorder with different prevalence estimates and agreement levels.

PMID- 15572188
TI  - Psychometric evaluation of the Children's Yale-Brown Obsessive-Compulsive Scale.
AB  - This study evaluated the psychometric properties of the Children's Yale-Brown
      Obsessive-Compulsive Scale (CY-BOCS). A total of 61 children and adolescents,
      aged 4-18 years, who were diagnosed with obsessive-compulsive disorder (OCD)
      participated. Thirty-seven of these children also participated in a second CY
      BOCS administration by the same rater an average of 41 days later. Good internal
      consistency and test-retest reliability were found for the CY-BOCS Obsession and
      Compulsion Severity Scores and the Total Score. CY-BOCS scores demonstrated
      strong correlations with clinician-rated measures of impairment, obsessions, and
      compulsions. In addition, CY-BOCS scores were moderately related to measures of
      depression, aggressive behavior, and symptoms of attention deficit hyperactivity
      disorder, but were not significantly related to clinician ratings of tics or self
      reports of general anxiety. Findings suggest that the CY-BOCS is a reliable and
      valid instrument for the assessment of childhood obsessions and compulsions.

PMID- 15572189
TI  - Estimating depression prevalence from the Beck Depression Inventory: is season of
      administration a moderator?
AB  - The existence of winter seasonal affective disorder (SAD) and its milder
      population variants implies that depression estimates in a given population may
      tend to be higher in winter than at other times of the year. The aim of this
      study was therefore to test whether depression prevalence estimates based on the
      Beck Depression Inventory (BDI) are systematically moderated by season of
      administration. Existing information from the screening phase of a multicentre
      investigation of depression prevalence provided the data for the study. Repeated
      cross-sectional BDI data from samples in the United Kingdom (n=1299), Finland
      (n=1352), Norway (n=2711) and Spain (n=1246) were analysed for month- and season
      of-administration effects. Whether data were measured continuously or as a
      dichotomous variable (BDI cutoff >/=13), there was no evidence of a systematic
      seasonal pattern in depression estimates across the four sites. No seasonal
      effects reached statistical significance at any single site, and trends in the
      association between winter and elevated BDI scores were positive in two sites (UK
      and Norway) and negative in two (Finland and Spain). Although limited by a post
      hoc analysis of existing data, this study provides the strongest evidence to date
      that season of administration is not a moderator of depression prevalence as
      estimated by the BDI.

PMID- 15572190
TI  - Prevalence of gastrointestinal symptoms in alcoholics and the relationship with
      alexithymia.
AB  - Alcohol abuse coincides with a wide variety of clinical, sociological and
      psychological features and symptoms. Gastrointestinal symptoms are also very
      common in alcoholics, but the reason is unclear. We aimed to determine the
      prevalence of alexithymia in alcoholics and furthermore if gastrointestinal
      symptoms were associated with alexithymia. Out of the 84 alcoholics who completed
      the alexithymia questionnaire (Toronto Alexithymia Scale, TAS20) and the standard
      gastrointestinal symptoms questionnaire, 92% reported gastrointestinal symptoms
      and 54% were alexithymic. Alcoholics above age 43 had more difficulty describing
      feelings (odds ratio=4.1, confidence interval=1.5-11.4). Almost all measured
      gastrointestinal symptoms in alcoholics were associated with scores on an
      alexithymia questionnaire.

PMID- 15572191
TI  - BisEDT and RIP act in synergy to prevent graft infections by resistant
      staphylococci.
AB  - Staphylococci are a major cause of infections associated with indwelling medical
      devices. Biofilm formation on these devices adds to the antibiotic resistance
      seen among clinical isolates. RNAIII-inhibiting peptide (RIP) is a heptapeptide
      that inhibits staphylococcal pathogenesis, including biofilm formation, by
      obstructing quorum sensing mechanisms. Bismuth ethanedithiol (BisEDT) also
      prevents biofilm formation at subinhibitory concentrations. RIP and BisEDT were
      combined to prevent infections in a rat graft model, using antibiotic sensitive
      and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis.
      BisEDT, RIP, or rifampin, or their combinations reduced the graft associated
      bacterial load over seven days. BisEDT-RIP was the best combination, reducing
      bacterial load to undetectable levels. BisEDT-RIP may prove useful for coating
      medical devices to prevent staphylococcal infections.

PMID- 15572192
TI  - Antimicrobial activity of Bac7 fragments against drug-resistant clinical
      isolates.
AB  - Ten peptides from 13 to 35 residues in length and covering the whole sequence of
      the Pro-rich peptide Bac7 were synthesized to identify the domain responsible for
      its antimicrobial activity. At least 16 residues of the highly cationic N
      terminal sequence were required to maintain the activity against Gram-negative
      bacteria. The fragments Bac7(1-35) and, to a lesser extent, Bac7(1-16) proved
      active against a panel of antibiotic-resistant clinical isolates of Gram-negative
      bacteria, with the notable exception of Burkholderia cepacia. In addition, when
      tested against fungi, the longer fragment was also active against collection
      strains and clinical isolates of Cryptococcus neoformans, but not towards
      clinical isolates of Candida albicans.

PMID- 15572193
TI  - Coccinin, an antifungal peptide with antiproliferative and HIV-1 reverse
      transcriptase inhibitory activities from large scarlet runner beans.
AB  - An antifungal peptide, designated coccinin, with a molecular mass of 7kDa and an
      N-terminal sequence resembling those of defensins, was purified from the seeds of
      large scarlet runner beans (Phaseolus coccineus cv. 'Major'). The peptide
      isolated was unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and
      Mono S. The peptide excerted antifungal activity on a number of fungal species
      including Botrytis cinerea, Coprinus comatus, Fusarium oxysporum, Mycosphaerella
      arachidicola, Physalospora piricola, and Rhizoctonia solani. It also inhibited
      proliferation in the leukemia cell lines HL60 and L1210, and reduced the activity
      of HIV-1 reverse transcriptase. However, it did not affect proliferation of mouse
      splenocytes.

PMID- 15572194
TI  - Structural and functional characterization of N-terminally blocked peptides
      isolated from the venom of the social wasp Polybia paulista.
AB  - Two novel peptides were isolated from the crude venom of the social wasp Polybia
      paulista, by using RP-HPLC under a gradient of MeCN from 5 to 60% (v/v) and named
      Polybine-I and -II. Further purification of these peptides under normal phase
      chromatography, rendered pure enough preparations to be sequenced by Edman
      degradation chemistry. However, both peptides did not interact with
      phenylisothiocyanate reagent, suggesting the existence of a chemically blocked N
      terminus. Therefore, the sequences of both peptides were assigned by ESI-MS/MS
      under CID conditions, as follows: Polybine-I Ac-SADLVKKIWDNPAL-NH2 (Mr 1610 Da)
      and Polybine-II Ac-SVDMVMKGLKIWPL-NH2 (Mr 1657 Da). During the tandem mass
      spectrometry experiments, a loss of 43 a.m.u. was observed from the N-terminal
      residue of each peptide, suggesting the acetylation of the N-terminus.
      Subsequently, the peptides with and without acetylation were synthesized on solid
      phase and submitted to functional characterizations; the biological activities
      investigated were: hemolysis, chemotaxis of polymorphonucleated leukocytes
      (PMNL), mast cell degranulation and antibiosis. The results revealed that the
      acetylated peptides exhibited more pronounced chemotaxis of PMNL cells and mast
      cell degranulation than the respective non-acetylated congeners; no hemolytic and
      antibiotic activities were observed, irrespective to the blockage or not of the
      alpha-amino groups of the N-terminal residues of each peptide. Therefore, the N
      terminal acetylation may be related to the increase of the inflammatory activity
      of both peptides.

PMID- 15572195
TI  - Comparative efficacy of VIP and analogs on activation and internalization of the
      recombinant VPAC2 receptor expressed in CHO cells.
AB  - Using a monoclonal antibody interacting with the extracellular amino-terminus of
      the human VPAC2 receptor but that did not interfere with ligand binding, we
      measured by flow cytometry receptor internalization and trafficking induced by
      full agonists, partial agonists and an antagonist in Chinese hamster ovary cells
      expressing the recombinant receptor. The agonists, but not the antagonist,
      induced a rapid, dose-dependent receptor internalization blocked by hypertonic
      sucrose that was more pronounced for the VIP analog N-hexanoyl-VIP (80%) than for
      VIP and Ro 25-1553 (50%) and the [A11]-VIP (20%). Re-expression of the receptors
      at the membrane was achieved within two hours after exposure to VIP and Ro 25
      1553 was blocked by 25 microM monensin but not by 10 microg/ml cycloheximide. Re
      expression was much slower after exposure to the acylated peptide and was blocked
      by preincubation with 25 microM monensin and 10 microg/ml cycloheximide.

PMID- 15572196
TI  - Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates:
      potential peptide radiotherapeutics for somatostatin receptor-positive cancers.
AB  - Derivatives of the somatostatin analogues octreotide and octreotate labeled with
      radioiosotopes are used in the diagnosis and therapy of somatostatin receptor
      (SSTR)-positive tumors. A method has been devised to synthesize {N-(4
      guanidinomethyl-3-iodobenzoyl)-Phe1-octreotate (GMIBO). Receptor binding assay
      and scatchard analysis yielded a Kd of 4.83 +/- 0.19 nM for this peptide.
      Derivatives of this peptide labeled with radioiodine ([*I]GMIBO) and the alpha
      particle-emitting radiohalogen 211At N-(3-[211At]astato-4-guanidinomethylbenzoyl)
      Phe1-octreotate; [211At]AGMBO} were prepared in a single step from a tin
      precursor in radiochemical yields of 30-35% and 15-20%, respectively. Paired
      label internalization assays performed with the SSTR-positive D341 Med human
      medulloblastoma cell line demonstrated that [125I]GMIBO and [211At]AGMBO were
      specifically internalized 20-40% more than Nalpha-(1-deoxy-D-fructosyl)-[131I]I
      Tyr3-octreotate ([131I]I-Glu-TOCA), the radioiodinated octreotide derivative
      previously shown to exhibit maximum internalization in this cell line. Uptake of
      [131I]GMIBO in D341 Med subcutaneous xenografts in a murine model (8.34 +/- 1.82
      versus 8.10 +/- 2.23% ID/g at 1h) and SSTR-expressing normal tissues was
      comparable to that of [125I]I-Glu-TOCA and was shown to be specific. However, the
      uptake of [131I]GMIBO also was substantially higher in liver (16.9 +/- 3.15
      versus 1.39 +/- 0.45% ID/g at 1 h) and in kidneys (44.33 +/- 6.47 versus 3.44 +/-
      0.68% ID/g at 1h) compared to that of [125I]I-Glu-TOCA. These data suggest that
      these novel peptide conjugates retain their specificity for SSTR both in vitro
      and in vivo; however, because of their higher accumulation in normal tissues they
      would be best applied in settings amenable to loco-regional administration such
      as medulloblastoma neoplastic meningitis.

PMID- 15572197
TI  - Assessing activation of the human neuropeptide FF2 receptor with a non
      radioactive GTP binding assay.
AB  - We have evaluated a novel, time-resolved fluorometric GTP binding assay for its
      suitability for functional screening of neuropeptide FF (NPFF) receptor ligands.
      Our results suggest that this assay, which relies on the use of a europium
      labeled GTP analogue, Eu-GTP, provides a powerful alternative to the
      [35S]guanosine-5'-O-(3-thio)triphosphate binding assay for assessing the
      functional properties of NPFF analogs. Further, we demonstrate that the
      tetrapeptide PMRF-NH2 exhibited high agonist potency at the NPFF2 receptor, and
      that the efficacies of this peptide and another shortened NPFF analog were
      greater than that of NPFF.

PMID- 15572198
TI  - Peptidergic and non-peptidergic innervation and vasomotor responses of human
      lenticulostriate and posterior cerebral arteries.
AB  - The aim of the present study was to compare in man the innervation pattern and
      the functional responses to neuronal messengers in medium sized lenticulostriate
      and branches of the posterior cerebral arteries (PCA). The majority of the nerve
      fibers found were sympathetic and displayed specific immunoreactivity for
      tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Only few nerve fibers
      displayed vasoactive intestinal polypeptide (VIP), calcitonin gene-related
      peptide (CGRP) and substance P (SP) immunoreactivity. In both arteries, the
      contractions induced by noradrenaline (NA), NPY and 5-hydroxytryptamine (5-HT)
      and the relaxant responses induced by acetylcholine (ACh), VIP and pituitary
      adenylate cyclase activating peptide-27 (PACAP) as well as CGRP and SP were
      compared in vitro. In conclusion, there was no major difference in innervation
      pattern or vasomotor sensitivity (pEC50 and pIC50 values) between the two
      vessels. However, the general pattern indicates stronger vasomotor responses
      (Emax and Imax) in the PCA branches as compared to the lenticulostriate arteries
      which may lend support for the clinical observation of a difference in stroke
      expression between the two vascular areas.

PMID- 15572199
TI  - Secretoneurin in the human aqueous humor and the absence of an effect of
      frequently used eye drops on the levels.
AB  - Secretoneurin (SN) was detected in the aqueous humor (AH) of patients treated
      topically with tobramycine eye drops alone or tobramycine and cyclosporine A,
      tobramycine and diclofenac or tobramycine and rimexolone. The levels of the
      peptide were found to be higher in the uninflamed human than in the rabbit
      aqueous humor which may be the result of species differences and/or age-related
      circumstances. Furthermore, they are approximately one hundred times higher than
      those of classical neuropeptides indicating release from nerve fibers and/or
      secretion from non-pigmented ciliary epithelium cells. Despite a slight tendency
      by rimexolone to decrease the levels, there was no significant effect seen for
      either of the drops. It must be considered that aminoglycosides are known to have
      toxic side effects and that they can influence the levels of SN which may be not
      diminished by low topical doses of corticosteroids or nonsteroidal
      antiinflammatory drugs. The high levels of the peptide are of relevance and may
      indicate a significant role of secretoneurin in the anterior segment of the eye.
      This should encourage performing functional studies.

PMID- 15572200
TI  - GSK3 involvement in amylin signaling in isolated rat soleus muscle.
AB  - Amylin can evoke insulin resistance by antagonizing insulin in a non-competitive
      manner. Here, we investigated the glycogenolytic effect of amylin in isolated
      skeletal muscle and compared it to the effects of a calcitonin gene-related
      peptide (CGRP). Amylin alone had no statistically significant effect on glucose
      transport. However, amylin decreased insulin-stimulated glucose transport by
      about 30%. The involvement of cAMP could not be detected at the concentrations
      shown to promote glycogenolysis. Previously, it has been shown that increased
      glycogen synthase kinase 3 (GSK3) activity plays a role in insulin resistance.
      Here, the ratio of GSK3 alpha:beta isoforms in rat soleus was found to be 1.2:1.
      We found that amylin increased GSK3alpha activity, which in turn led to increased
      phosphorylation of glycogen synthase and decreased glycogen synthesis de novo.

PMID- 15572201
TI  - The F1-ATPase beta-subunit is the putative enterostatin receptor.
AB  - It has been suggested that the F1-ATPase beta-subunit is the enterostatin
      receptor. We investigated the binding activity of the purified protein with a
      labeled antagonist, beta-casomorphin1-7, in the absence and presence of cold
      enterostatin. 125I-beta-casomorphin1-7 weakly binds to the rat F1-ATPase beta
      subunit. Binding was promoted by low concentrations of cold enterostatin but
      displaced by higher concentrations. To study the relationship between binding
      activity and feeding behavior, we examined the ability of a number of
      enterostatin analogs to affect beta-casomorphin1-7 binding to the F1-ATPase beta
      subunit. Peptides that suppressed food intake promoted beta-casomorphin1-7
      binding whereas peptides that stimulated food intake or did not affect the food
      intake displaced beta-casomorphin1-7 binding. Surface plasmon resonance
      measurements show that the beta-subunit of F1-ATPase binds immobilized
      enterostatin with a dissociation constant of 150 nM, where no binding could be
      detected for the assembled F1-ATPase complex. Western blot analysis showed the F1
      ATPase beta-subunit was present on plasma and mitochondrial membranes of rat
      liver and amygdala. The data provides evidence that the F1-ATPase beta-subunit is
      the enterostatin receptor and suggests that enterostatin and beta-casomorphin1-7
      bind to distinct sites on the protein.

PMID- 15572202
TI  - The anorectic effect of neurotensin is mediated via a histamine H1 receptor in
      mice.
AB  - Neurotensin (NT), a tridecapeptide found in the mammalian brain and peripheral
      tissues, induces a decrease in food intake after central administration. In this
      investigation, we examine whether the histaminergic system is involved in NT
      induced suppression of feeding. Intracerebroventricular injection of NT (0.1-1
      nmol/mouse) led to dose-dependent inhibition of food intake in fasted ddY mice.
      The anorectic effect induced by NT (0.1 nmol/mouse) was ameliorated upon co
      administration of pyrilamine (3 nmol/mouse), an antagonist for histomine H1
      receptor. The NT-induced anorectic effect was partially ameliorated in H1
      knockout mice. The findings suggest that the H1 receptor in part mediates the NT
      induced suppression of food intake.

PMID- 15572203
TI  - Effect of neuropeptide Y microinjected into the hypothalamus on ethanol
      consumption.
AB  - Guide cannula were implanted in rats aimed at the paraventricular nucleus (PVN)
      of the hypothalamus for microinjection of neuropeptide Y (NPY), D-NPY27-36, or
      vehicle. In the Wistar rat, there was no significant effect on the consumption of
      ethanol. In Myers' high ethanol preferring (mHEP) rats, D-NPY27-36 caused a
      significant 54% decrease in ethanol consumption from baseline, but the response
      was not different from vehicle. NPY-induced feeding in satiated Wistar rats, was
      blocked by a Y1 receptor antagonist, D-NPY27-3). D-NPY27-36 decreased 78% feeding
      in food-deprived rats. Thus, neither the Wistar nor the mHEP rat perceives
      ethanol as a source of calories comparable to food.

PMID- 15572204
TI  - Changes of hypothalamic alpha-MSH and CART peptide expression in diet-induced
      obese rats.
AB  - Two hypothalamic peptides, cocaine and amphetamine-regulated transcript (CART)
      and alpha-melanocyte-stimulating hormone (alpha-MSH), recognized as anorexigenic
      neuropeptides to suppress the feeding behavior, were monitored in rats fed with a
      high-fat (HIF) diet for 14 weeks. While half of the rats developed obesity (diet
      induced obese, DIO), some did not (diet resistant, DR). Compared to the DR rats
      and the control rats (fed with standard chow), DIO rats were accompanied by a
      markedly higher energy intake and a decrease in the number of neurons carrying
      alpha-MSH and CART peptide in the arcuate nucleus of the hypothalamus. Failure of
      hypothalamic anorexigenic peptides CART and alpha-MSH to increase their content
      in response to HIF diet may play a key role for overly high energy consumption,
      resulting in obesity.

PMID- 15572205
TI  - Immunohistochemical and genomic evidence for the involvement of hypothalamic
      neuropeptide Y (NPY) in phenylpropranolamine-mediated appetite suppression.
AB  - Phenylpropanolamine (PPA) is an appetite suppressant. The mechanism for the
      anorectic effect of PPA has been attributed to its action on the site of
      hypothalamic paraventriculum. Neuropeptide Y (NPY) is an appetite stimulant that
      is widely distributed in the site of hypothalamus. It is not clear whether
      hypothalamic NPY is involved in the anorectic action of PPA. This study was aimed
      to investigate the mechanism underlying the involvement of NPY gene in the
      anorectic action of PPA. Results revealed that PPA treatment in rats could
      decrease both NPY content and mRNA level in the hypothalamus. In addition, the
      expression of NPY immunoreactivity following PPA treatment was decreased in areas
      of hypothalamic arcuate nucleus, paraventricular nucleus and periventricular area
      using immunohistochemical staining, suggesting an involvement of NPYergic pathway
      in the action of PPA anorexia. Our results provided immunohistochemical and
      genomic evidence to suggest that PPA might reduce feeding by altering NPY gene
      expression.

PMID- 15572206
TI  - Effects of hexarelin against acid-independent and acid-dependent ulcerogens in
      the rat.
AB  - The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin
      (Hexa) administration, against gastric ulcers induced by ethanol (50%, 1
      ml/rat/os) or Indomethacin (20 mg/kg/os) were examined in conscious rats. Hexa at
      1 nmol/rat, icv or 10 nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32%
      respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin
      induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced
      ulcers was removed by the GHS-R antagonist (D-Lys3)-GRPR-6 and by the inhibitor
      of NO-synthase (NOS) Nomega-nitro-L-arginine methyl ester. Semiquantitative RT
      PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS
      derived NO and the increase of constitutive-derived NO are relevant for the
      gastroprotection of Hexa against ethanol-induced gastric damage.

PMID- 15572207
TI  - Regulation of ghrelin gene expression in stomach and feeding response to a
      ghrelin analogue in two strains of rats.
AB  - Ghrelin is a peptide produced by the stomach and released into the circulation.
      As a natural ligand of the growth hormone secretagogue (GHS) receptor, it
      stimulates growth hormone secretion but it also stimulates feeding in humans and
      rodents. The orexigenic effect of ghrelin has been related to AgRP/NPY and orexin
      pathways. We proposed that ghrelin might be involved in the susceptibility to
      diet induced obesity and in the regulation of macronutrient selection. We have
      investigated these hypotheses in two strains of rat, the Osborne-Mendel (OM) rat
      that prefers diets high in fat and is sensitive to dietary obesity and the S5B/P1
      (S5B) rat that prefers a low fat diet and is resistant to high fat diet induced
      obesity. OM and S5B rats were adapted to a choice of high fat (HF) and low fat
      (LF) diet for 2 weeks. GHRP-2, an analogue of ghrelin, was injected
      intraperitoneally into satiated and 24 h fasted rats at doses of 10, 30 and 90
      nmol. Food intake was measured over the next 4 h period. In satiated S5B rats,
      GHRP-2 stimulated intake of the LF diet in a dose dependent manner but did not
      affect the intake of the HF diet. In satiated OM rats, 90 nmol of GHRP-2
      stimulated HF intake. In contrast, neither fasted OM nor S5B rats increased the
      intake of either HF or LF diet in response to GHRP-2. Fasting for 18 h induced a
      large rise in ghrelin mRNA in stomach of OM rats but not in S5B rats. There were
      no significant differences in plasma total ghrelin. An increase in ghrelin mRNA
      in stomach immediately before the onset of the dark cycle was observed in OM but
      not in S5B rats. Active ghrelin level was significantly affected by different
      feeding conditions in both OM and S5B rats adapted on HF diet with a trend to
      increase after 48 h of fasting and to decline to basal levels following 10 h of
      refeeding. These data suggest that ghrelin stimulates the intake of the preferred
      macronutrient. In addition, a differential regulation of ghrelin gene expression
      between OM and S5B rats may be important in their differential sensitivity to HF
      diet-induced obesity.

PMID- 15572208
TI  - Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo.
AB  - Recent evidence indicates that ghrelin, an endogenous ligand of the growth
      hormone secretagogue receptor (GHS-R), is highly expressed in the cardiovascular
      system, and in this study we addressed the possibility that ghrelin may affect
      angiogenesis in vitro and in vivo. Reverse transcription-polymerase chain
      reaction showed that human umbilical vein endothelial cells (HUVECs) express
      ghrelin and GHS-R mRNAs. Ghrelin inhibited FGF-2-induced proliferation of HUVECs
      cultured in vitro, the maximal effective concentration being 10(-8) M, and this
      effect was annulled by the GHS-R antagonist D-Lys3-growth hormone releasing
      peptide-6. FGF-2 stimulated HUVEC cultured on Matrigel to form capillary-like
      structures, and ghrelin (10(-8) M) suppressed this effect. In the chick embryo
      chorioallantoic membrane in vivo assay, FGF-2 induced a strong angiogenic
      response, which was counteracted by ghrelin (500 ng). Taken together, these
      findings suggest that ghrelin acts as an angiostatic molecule and indicate that
      its activity is comparable to that of a well-known angiostatic agent, i.e.,
      vinblastine. The antiangiogenic activity of ghrelin deserves further
      investigations, alone or together with other antiangiogenic agents, for the
      treatment of pathological conditions characterized by enhanced angiogenesis.

PMID- 15572209
TI  - Leptin fluctuates in intestinal ischemia-reperfusion injury as inflammatory
      cytokine.
AB  - As leptin is an active mediator mainly secreted by adipose tissue and is closely
      related with energy metabolism, we evaluate both the changes of leptin levels in
      serum and adipose tissue with a concise radioimmunoassay and the changes of
      leptin mRNA expression in adipose tissue with RT-PCR, during the severe metabolic
      impediment in rat intestinal ischemia-reperfusion (I/R) injury. Results show that
      not only leptin levels in serum and adipose tissue but also its mRNA expression
      in adipose tissue undergo a fluctuation according to different injury times.
      Therefore, we conclude that leptin has a time-dependent response to acute
      inflammatory stimuli and acts as an anti-inflammatory cytokine.

PMID- 15572210
TI  - Effect of insulin-like growth factors (IGF), FSH, and leptin on IGF-binding
      protein mRNA expression in bovine granulosa and theca cells: quantitative
      detection by real-time PCR.
AB  - To determine if insulin-like growth factor (IGF)-1 and -2, FSH, or leptin alter
      IGF-binding protein (IGFBP)-2, -3, -4, and -5 mRNA levels in bovine granulosa and
      (or) theca cells, granulosa and theca cells were collected from bovine ovarian
      follicles, plated for 48 h in 10% FCS and then treated for 24 h in serum-free
      medium containing various hormone treatments arranged in three different
      experiments. Amounts of IGFBP-2, -3, -4, and -5 mRNA were quantitated using
      fluorescent quantitative real-time RT-PCR. Neither 100 ng/ml of IGF-1 nor IGF-2
      had an effect (P > 0.10) on IGFBP-2, -3, -4, or -5 mRNA levels in small-follicle
      (1-5 mm; Experiment 1) granulosa cells. In large-follicle (>7.9 mm; Experiment 2)
      granulosa cells, 100 ng/ml of IGF-1 increased (P < 0.05) IGFBP-2 mRNA levels
      above controls and 3 ng/ml of IGF-1; 100 ng/ml of IGF-1 also decreased (P < 0.10)
      IGFBP-5 mRNA levels compared to 3 ng/ml of IGF-1 or FSH or 100 ng/ml leptin,
      while 100 ng/ml of IGF-2 had no effect (P > 0.10) on IGFBP-2, -3, -4, and -5 mRNA
      levels (Experiment 2). At the doses tested, leptin and FSH had no effect (P >
      0.10) on IGFBP-2, -3, -4, and -5 mRNA levels in large-follicle granulosa cells.
      In theca cells, IGF-2 decreased (P < 0.05) IGFBP-2 mRNA levels, but had no effect
      on IGFBP-3 or -4 mRNA expression (Exp. 3); IGF-1 did not affect (P > 0.10) thecal
      IGFBP-2, -3 or -4 mRNA levels. In contrast, IGF-1 but not IGF-2 increased (P <
      0.01) thecal IGFBP-5 mRNA levels. Ligand blotting revealed that both IGF-1 and -2
      increased IGFBP-2 and -5 (protein) and had no effect on IGFBP-3 (protein),
      whereas IGF-1 (but not IGF-2) increased IGFBP-4 (protein), suggesting IGFBP-2, 
      4, and -5 are post-transcriptionally regulated. These results suggest that
      expression of IGFBP-2, -3, -4, and -5 mRNA by granulosa and theca cells are
      differentially regulated by IGF-1 and -2, therefore discretely modulating the
      amount of bio-available IGFs to these cells depending upon the specific hormonal
      milieu.

PMID- 15572211
TI  - Endogenous opiates and behavior: 2003.
AB  - This paper is the 26th consecutive installment of the annual review of research
      concerning the endogenous opioid system, now spanning over a quarter-century of
      research. It summarizes papers published during 2003 that studied the behavioral
      effects of molecular, pharmacological and genetic manipulation of opioid
      peptides, opioid receptors, opioid agonists and opioid antagonists. The
      particular topics that continue to be covered include the molecular-biochemical
      effects and neurochemical localization studies of endogenous opioids and their
      receptors related to behavior (Section 2), and the roles of these opioid peptides
      and receptors in pain and analgesia (Section 3); stress and social status
      (Section 4); tolerance and dependence (Section 5); learning and memory (Section
      6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8);
      sexual activity and hormones, pregnancy, development and endocrinology (Section
      9); mental illness and mood (Section 10); seizures and neurologic disorders
      (Section 11); electrical-related activity and neurophysiology (Section 12);
      general activity and locomotion (Section 13); gastrointestinal, renal and hepatic
      functions (Section 14); cardiovascular responses (Section 15); respiration and
      thermoregulation (Section 16); and immunological responses (Section 17).

PMID- 15572212
TI  - Effects of peptides, with emphasis on feeding, pain, and behavior A 5-year (1999
      2003) review of publications in Peptides.
AB  - Novel effects of naturally occurring peptides are continuing to be discovered,
      and their mechanisms of actions as well as interactions with other substances,
      organs, and systems have been elucidated. Synthetic analogs may have actions
      similar or antagonistic to the endogenous peptides, and both the native peptides
      and analogs have potential as drugs or drug targets. The journal Peptides
      publishes many leading articles on the structure-activity relationship of
      peptides as well as outstanding reviews on some families of peptides.
      Complementary to the reviews, here we extract information from the original
      papers published during the past five years in Peptides (1999-2003) to summarize
      the effects of different classes of peptides, their modulation by other chemicals
      and various pathophysiological states, and the mechanisms by which the effects
      are exerted. Special attention is given to peptides related to feeding, pain, and
      other behaviors. By presenting in condensed form the effects of peptides which
      are essential for systems biology, we hope that this summary of existing
      knowledge will encourage additional novel research to be presented in Peptides.

PMID- 15572213
TI  - Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative
      disorders.
AB  - We summarize the current knowledge on molecular alterations in myeloproliferative
      disorders (MPD), in particular altered in vitro responses of progenitor cells,
      cytokine signaling, gene expression patterns and genetic lesions. Newly
      characterized markers, such as altered expression of polycythemia rubra vera-1
      (PRV-1) and the thrombopoietin receptor (c-MPL) as well as deletions on
      chromosome 20q (del20q) and loss of heterozygosity on chromosome 9p (9pLOH)
      provide an opportunity to diagnose and identify subpopulations of MPD patients.
      Furthermore, we review familial syndromes that share phenotypic features with
      sporadic MPD. In some of these families, mutations in the genes for
      thrombopoietin (TPO), c-MPL, EPO-receptor and the von Hippel-Lindau (VHL) gene
      have been shown to cause the disease. However, in the majority of familial cases
      the molecular causes remain unknown. Some of these families display clonal
      hematopoiesis and other features previously only found in sporadic MPD.
      Elucidating the molecular defect(s) in these pedigrees will likely be relevant
      for understanding sporadic MPD pathogenesis.

PMID- 15572214
TI  - Mutating factor VIII: lessons from structure to function.
AB  - Factor VIII, a metal ion-dependent heterodimer, circulates in complex with von
      Willebrand factor. At sites of vessel wall damage, this procofactor is activated
      to factor VIIIa by limited proteolysis and assembles onto an anionic phospholipid
      surface in complex with factor IXa to form the intrinsic factor Xase; an enzyme
      complex that efficiently converts factor X to factor Xa during the propagation
      phase of coagulation. Factor Xase activity is down-regulated by mechanisms that
      include self-dampening by dissociation of a critical factor VIIIa subunit and
      proteolytic inactivation by the activated protein C pathway. Recent studies
      identify putative metal ion coordination sites as well as ligands involved in the
      catabolism of the activated and procofactor forms of the protein. Our knowledge
      of these multiple intra- and inter-molecular interactions has been facilitated by
      the application of naturally occurring and site-directed mutations to study
      factor VIII structure and function. In this review, we document important and
      novel contributions following this line of investigation.

PMID- 15572215
TI  - Stem cell plasticity.
AB  - The central dogma in stem cell biology has been that cells isolated from a
      particular tissue can renew and differentiate into lineages of the tissue it
      resides in. Several studies have challenged this idea by demonstrating that
      tissue specific cell have considerable plasticity and can cross-lineage
      restriction boundary and give rise to cell types of other lineages. However, the
      lack of a clear definition for plasticity has led to confusion with several
      reports failing to demonstrate that a single cell can indeed differentiate into
      multiple lineages at significant levels. Further, differences between results
      obtained in different labs has cast doubt on some results and several studies
      still await independent confirmation. In this review, we critically evaluate
      studies that report stem cell plasticity using three rigid criteria to define
      stem cell plasticity; differentiation of a single cell into multiple cell
      lineages, functionality of differentiated cells in vitro and in vivo, robust and
      persistent engraft of transplanted cells.

PMID- 15572216
TI  - Splenic marginal zone lymphoma.
AB  - Splenic marginal zone lymphoma (SMZL) is an indolent B cell malignancy usually
      involving spleen, bone marrow and blood. The disease presents as an incidental
      finding or with symptoms of splenic enlargement or anaemia. Diagnosis is based on
      a combination of lymphocyte morphology, immunophenotype and marrow and /or
      splenic histology. There is no genetic abnormality specific for SMZL, but
      deletions of chromosome 7q are the commonest abnormality and are found in 30-50%
      of cases. SMZL cells may have either mutated or unmutated immunoglobulin variable
      region genes and probably arise from different subsets of splenic marginal zone B
      cells. Prognostic factors are poorly defined and only loss or mutation of the p53
      gene is consistently associated with a poor outcome. Therapeutic options include
      splenectomy, splenic irradiation, alkylating agents, purine analogues or anti
      CD20 antibody. The median survival is 10-13 years and most disease-related deaths
      are associated with transformation to diffuse large cell lymphoma.

PMID- 15572217
TI  - Idiopathic cyclic thrombocytopenia.
AB  - Cyclic thrombocytopenia (CTP) is an uncommon disorder characterized by periodic
      fluctuations in platelet counts, typically resulting in episodes of
      thrombocytopenia alternating with normal platelet counts. While some CTP cases
      are associated with a primary hematologic disease, most are idiopathic. Patients
      with CTP are frequently misdiagnosed as idiopathic thrombocytopenic purpura (ITP)
      because CTP has clinical features very similar to ITP. When evaluating patients
      with suspected ITP, CTP should always be included in the differential diagnoses
      because CTP generally does not respond to standard ITP treatments, including
      corticosteroids, splenectomy, and intravenous immunoglobulin. Two clinical
      features relatively unique to CTP besides periodic thrombocytopenia are rebound
      thrombocytosis unrelated to recent splenectomy and platelet nadirs occurring
      during menses. When a diagnosis of CTP is made, patients must be offered a period
      of observation, as many may not require treatment. If treatment is clinically
      indicated, the literature suggests that hormonal therapy provides the best
      response.

PMID- 15572218
TI  - Quantifying ozone uptake and its effects on the stand level of common beech
      (Fagus sylvatica L.) in Southern Germany.
AB  - Stand level O(3) fluxes were calculated using water balance calculations for 21
      Common beech (Fagus sylvatica L.) stands and O(3) data from 20 monitoring
      stations in Southern Germany. For this intention, the daily loss of water by
      evapotranspiration per stand area was set against the daily O(3) uptake. During
      the last 30 years, O(3) uptake ranges between 0 and 187 mmol ha(-1) d(-1) per
      stand area. Cumulative O(3) uptake (CUO(3)), ranging between 0.1 and 0.7 mmol m(
      2) yr(-1) per stand area, shows increasing trends since 1971 with considerably
      greater values at high altitudes. Effects in radial growth were used to derive an
      initial approximate critical threshold value for O(3) impacts on the vitality and
      growth of mature beech stands in Southern Germany. It is concluded that this
      concept of O(3) flux estimation in combination with dendroecological analyses
      offers both a site specific and regional applicable approach to derive new
      critical levels for O(3).

PMID- 15572219
TI  - Validated sampling strategy for assessing contaminants in soil stockpiles.
AB  - Dutch legislation on the reuse of soil requires a sampling strategy to determine
      the degree of contamination. This sampling strategy was developed in three
      stages. Its main aim is to obtain a single analytical result, representative of
      the true mean concentration of the soil stockpile. The development process
      started with an investigation into how sample pre-treatment could be used to
      obtain representative results from composite samples of heterogeneous soil
      stockpiles. Combining a large number of random increments allows stockpile
      heterogeneity to be fully represented in the sample. The resulting pre-treatment
      method was then combined with a theoretical approach to determine the necessary
      number of increments per composite sample. At the second stage, the sampling
      strategy was evaluated using computerised models of contaminant heterogeneity in
      soil stockpiles. The now theoretically based sampling strategy was implemented by
      the Netherlands Centre for Soil Treatment in 1995. It was applied to all types of
      soil stockpiles, ranging from clean to heavily contaminated, over a period of
      four years. This resulted in a database containing the analytical results of 2570
      soil stockpiles. At the final stage these results were used for a thorough
      validation of the sampling strategy. It was concluded that the model approach has
      indeed resulted in a sampling strategy that achieves analytical results
      representative of the mean concentration of soil stockpiles.

PMID- 15572220
TI  - Mercury transfer from fish carcasses to scavengers in boreal lakes: the use of
      stable isotopes of mercury.
AB  - Scavengers play an important role in the flow of energy, matter and pollutants
      through food webs. For methylmercury (MeHg), which biomagnifies along food
      chains, the movement of this metal from fish carcasses to aquatic scavengers has
      never been demonstrated. We measured the transfer of MeHg from fish carcasses to
      scavenging leeches in two lakes and in the laboratory. The results of a field
      experiment indicated that leeches were attracted to fish carcasses and that their
      Hg concentrations increased by as much as a factor of 5 during the time that Hg
      rich fish were available for consumption. Under controlled conditions, we exposed
      leeches to (202)Hg-labelled fish that had been marked in situ following a whole
      lake (202)Hg addition. Leeches rapidly accumulated Hg from carcasses, and within
      two weeks assumed the isotopic signature of the carcasses. Necrophagous
      invertebrates could therefore return Hg from fish carcasses to other trophic
      levels in lakes.

PMID- 15572221
TI  - Study of calcium-dependent lead-tolerance on plants differing in their level of
      Ca-deficiency tolerance.
AB  - The main aim of the study was to determine the role of calcium in the
      amelioration of lead toxic effects in plants with accordingly high/low level of
      Pb-tolerance and high/low Ca-deficiency tolerance. The study was performed on
      maize, rye, tomato and mustard. Plants were cultivated in modified Knop's
      solution. They were subjected to Ca-deficiency, and to lead nitrate administered
      in the presence of four calcium nitrate concentrations 3.0, 2.4, 1.2, 0.3mM. Lead
      tolerance and tolerance to Ca-deficiency were determined, as were concentration
      of the studied elements in plant tissues, and the Pb deposition pattern at the
      ultrastructural level (electron microscopy study, X-ray microanalysis). In all
      studied plants, lead toxicity increased as medium calcium content decreased,
      however, only in the Ca-deficiency sensitive mustard with low Pb-tolerance was it
      accompanied by a rise in tissue lead concentration. In contrast, lead root and
      shoot levels did not increase in the highly Ca-deficiency tolerant tomato,
      mustard and rye with high Pb-tolerance irrespective of the Ca(2+) regimens
      applied. Thus, in these plants, lead's unfavourable effects resulted only from
      the higher toxicity of the same amount of lead in tissues at low calcium in the
      medium. Of particular relevance is the finding by electron microscopy and X-ray
      microanalysis, that under low calcium in both highly Ca-deficiency tolerant and
      Ca-deficiency sensitive plants, less efficient Pb(2+) detoxification was
      accompanied by the restriction of the formation of large lead deposits in cell
      walls. Obtained results are novel in demonstrating calcium involvement in the
      lead deposition in the cell wall, thus in the regulation of the internal lead
      detoxification.

PMID- 15572222
TI  - Sorption studies of chloroanilines on kaolinite and montmorillonite.
AB  - Batch experiments have been performed in order to evaluate the ability of the two
      reference clays kaolinite (KGa-1) and Na-montmorillonite (SWy-1) to retain three
      representative chloroanilines: 3-chloroaniline, 3,4-dichloroaniline and 2,4,6
      trichloroaniline. Systems containing the clay mineral and the pollutant solution
      (at concentration levels ranging between 1.0 and 10.0mg/L) were considered and RP
      HPLC methods were employed to follow the sorption processes as a function of
      time. The results indicate that montmorillonite shows a general higher sorption
      capacity with respect to kaolinite and that for both the reference clays, in the
      concentration range investigated, the amount of pollutant sorbed increases with
      concentration. The sorption coefficient K(d) ranges between 0.0030 L/g for the
      system 3-chloroaniline-kaolinite and 0.0488L/g for the system 2,4,6
      trichloroaniline-montmorrillonite. The most lipophilic trichloroaniline shows the
      greater sorption. X-ray analyses suggest for kaolinite a preferential sorption
      onto the mineral surface, while for montmorillonite a progressive swelling of the
      structure is observed, likely due to sorption processes that also take place in
      the interlayer.

PMID- 15572223
TI  - Bioaccumulation of 51Cr, 63Ni and 14C in Baltic Sea benthos.
AB  - The Baltic Sea is a species-poor, semi-enclosed, brackish sea, whose sediments
      contain a wide range of contaminants, including sediment-associated metals and
      radionuclides. In this study, we have examined and compared bioaccumulation
      kinetics and assimilation efficiencies of sediment-associated (51)Cr, (63)Ni and
      (14)C in three key benthic invertebrates (the deposit-feeding Monoporeia affinis,
      the facultative deposit-feeding Macoma baltica, and the omnivorous Halicryptus
      spinulosus). Our results demonstrate that (i) all radionuclides were accumulated,
      (ii) the different radionuclides were accumulated to various extents, (iii) small
      changes in organic carbon concentration can influence the accumulation, and (iv)
      the degree of accumulation differed only slightly between species. These
      processes, together with sediment resuspension and bioturbation, may remobilise
      trace metals from the sediment to the water and to higher trophic levels, and
      therefore should be taken into account in exposure models and ERAs.

PMID- 15572224
TI  - Do tubificid worms influence the fate of organic matter and pollutants in
      stormwater sediments?
AB  - In urban area, management of stormwater leads to the accumulation of polluted
      sediments at the water-sediment interface of various aquatic ecosystems. In many
      cases, these sediments are colonised by dense populations of tubificid worms.
      However, the influence of tubificid worms on the fate of stormwater sediments has
      never been tackled. The aim of this study was to measure in sediment columns the
      influence of tubificid worms on sediment reworking, organic matter processing
      (O(2) uptake and release of NH(4)(+), NO(3)(-), PO(4)(3-), and dissolved organic
      carbon), release of hydrocarbons and heavy metals, and microbial characteristics.
      Results showed that tubificid worms increased the release of NH(4)(+), PO(4)(3-),
      and dissolved organic carbon by 2-, 4-, and 3-fold, respectively. O(2) uptake
      also increased by more than 35% due to tubificid activity. The increase in the
      percentages of active bacteria and hydrolytic activity in the presence of worms
      indicated that the higher sediment respiration was caused by the stimulation of
      microbial communities. A reduction of the number of sulphate-reducing bacteria in
      the uppermost layers of the sediment was attributed to the penetration of O(2)
      due to worm activity. These significant effects of tubificid worms were probably
      linked to the dense network of burrows, which enhanced the exchange surface
      between the water column and the sediment. No release of heavy metals and
      hydrocarbons to the water phase was detected in the sediment columns.
      Understanding the fate and effect of organic stormwater sediments in the natural
      environment requires the integration of the role of bioturbation in urban
      pollution studies.

PMID- 15572225
TI  - Release behavior of triazine residues in stabilised contaminated soils.
AB  - This paper reports the release behavior of two triazines (atrazine and simazine)
      in stabilised soils from a pesticide-contaminated site in South Australia. The
      soils were contaminated with a range of pesticides, especially with triazine
      herbicides. With multiple extractions of each soil sample with deionised water
      (eight in total), 15% of atrazine and 4% of simazine residues were recovered,
      resulting in very high concentrations of the two herbicides in leachate. The
      presence of small fractions of surfactants was found to further enhance the
      release of the residues. Methanol content up to 10% did not substantially
      influence the concentration of simazine and atrazine released. The study
      demonstrated that while the stabilisation of contaminated soil with particulate
      activated carbon (5%) and cement mix (15%) was effective in locking the residues
      of some pesticides, it failed to immobilise triazine herbicides residues
      completely. Given the higher water solubility of these herbicides than other
      compounds more effective strategies to immobilise their residues is needed.

PMID- 15572226
TI  - Mercury contamination in human hair and fish from Cambodia: levels, specific
      accumulation and risk assessment.
AB  - Mercury (Hg) concentrations in human hair and fish samples from Phnom Penh, Kien
      Svay, Tomnup Rolork and Batrong, Cambodia, collected in November 1999 and
      December 2000 were determined to understand the status of contamination, and age-
      and sex-dependent accumulation in humans and to assess the intake of mercury via
      fish consumption. Mercury concentrations in human hair ranged from 0.54 to
      190mug/g dry wt. About 3% of the samples contained Hg levels exceeding the no
      observed adverse effects level (NOAEL) of WHO (50mug/g) and the levels in some
      hair samples of women also exceeded the NOAEL (10mug/g) associated with fetus
      neurotoxicity. A weak but significant positive correlation was observed between
      age and Hg levels in hair of residents. Mercury concentrations in muscle of
      marine and freshwater fish from Cambodia ranged from <0.01 to 0.96mug/g wet wt.
      Mercury intake rates were estimated on the basis of the Hg content in fish and
      daily fish consumption. Three samples of marine fish including sharp-tooth
      snapper and obtuse barracuda, and one sample of sharp-tooth snapper exceeded the
      guidelines by US EPA and by Joint FAO/WHO Expert Committee on Food Additives
      (JECFA), respectively, which indicates that some fish specimens examined (9% and
      3% for US EPA and JECFA guidelines, respectively) were hazardous for consumption
      at the ingestion rate of Cambodian people (32.6g/day). It is suggested that fish
      is probably the main source of Hg for Cambodian people. However, extremely high
      Hg concentrations were observed in some individuals and could not be explained by
      Hg intake from fish consumption, indicating some other contamination sources of
      Hg in Cambodia.

PMID- 15572227
TI  - Impact of a flood disaster on sediment toxicity in a major river system--the Elbe
      flood 2002 as a case study.
AB  - The ecotoxicological implications of a flooding disaster were investigated with
      the exceptional Elbe flood in August 2002 as an example. Sediment samples were
      taken shortly after the flood at 37 sites. For toxicity assessment the midge
      Chironomus riparius (Insecta) and the mudsnail Potamopyrgus antipodarum
      (Gastropoda) were exposed to the sediment samples for 28 days. For a subset of 19
      sampling sites, the contamination level and the biological response of both
      species were also recorded before the flood in 2000. The direct comparison of
      biological responses at identical sites revealed significant differences for
      samples taken before and immediately after the flood. After flood sediments of
      the river Elbe caused both higher emergence rates in the midge and higher numbers
      of embryos in the mudsnail. Contrary to expectations the toxicity of the
      sediments decreased after the flood, probably because of a dilution of toxic
      substances along the river Elbe and a reduction in bioavailability of pollutants
      as a result of increasing TOC values after the flood.

PMID- 15572228
TI  - Contamination of rivers in Tianjin, China by polycyclic aromatic hydrocarbons.
AB  - Tianjin urban/industrial complex is highly polluted by some persistent organic
      pollutants. In this study, the levels of 16 priority polycyclic aromatic
      hydrocarbons (PAHs) were tested in sediment, water, and suspended particulate
      matter (SPM) samples in 10 rivers in Tianjin. The total concentration of 16 PAHs
      varied from 0.787 to 1943 microg/g dry weight in sediment, from 45.81 to 1272
      ng/L in water, and from 0.938 to 64.2 microg/g dry weight in SPM. The levels of
      PAHs in these media are high in comparison with values reported from other river
      and marine systems. Variability of total concentrations of PAHs in sediment,
      water, and SPM from nine different rivers is consistent with each other. No
      obvious trends of total PAHs concentration variations were found between upstream
      and downstream sediment, water, and SPM samples for most rivers, which indicate
      local inputs and disturbances along these rivers. The spatial distributions of
      three-phase PAHs are very similar to each other, and they are also similar to
      those found in topsoil. However, their chemical profiles are significantly
      different from that of topsoil. The change of profiles is consistent with the
      different aqueous transport capability of 16 PAHs. Low molecular weight PAHs
      predomination suggests a relatively recent local source and coal combustion
      source of PAHs in the study area.

PMID- 15572229
TI  - Bioaccumulation of PCBs in the cuttlefish Sepia officinalis from seawater,
      sediment and food pathways.
AB  - The cuttlefish Sepia officinalis was selected as a model cephalopod to study PCB
      bioaccumulation via seawater, sediments and food. Newly hatched, juvenile
      cuttlefish were exposed for 17 days to environmentally realistic concentrations
      of (14)C-labeled 2,2',4,4',5,5'-hexachlorobiphenyl (PCB#153) (18 ng PCB l(-1)
      seawater; 30 ng PCB g(-1) dry wt sediments; Artemia salina exposed to 18 ng PCB
      l(-1) seawater). Accumulation of PCB#153 was followed in three body compartments:
      digestive gland, cuttlebone and the combined remaining tissues. Results showed
      that (1) uptake kinetics were source- and body compartment-dependent, (2) for
      each body compartment, the accumulation was far greater when S. officinalis was
      exposed via seawater, (3) the cuttlebone accumulated little of the contaminant
      regardless of the source, and (4) the PCB congener showed a similar distribution
      pattern among the different body compartments following exposure to contaminated
      seawater, sediment or food with the lowest concentrations in the cuttlebone and
      the highest in the remaining tissues. The use of radiotracer techniques allowed
      delineating PCB kinetics in small whole organisms as well as in their separate
      tissues. The results underscore the enhanced ability of cephalopods to
      concentrate organic pollutants such as PCBs, and raise the question of potential
      risk to their predators in contaminated areas.

PMID- 15572230
TI  - The combined effect of lead exposure and high or low dietary calcium on health
      and immunocompetence in the zebra finch (Taeniopygia guttata).
AB  - The widespread contamination by lead and the acidification of the environment ask
      for a better understanding of the effects of the interaction between lead and
      calcium on various aspects of health, including disease defense, in wildlife.
      Here, we investigated the effects of chronic exposure to sublethal levels of
      lead, combined with high or low dietary calcium, on health and several components
      of immunity in male and female zebra finches (Taeniopygia guttata). Thirty
      individuals of each sex were randomly assigned to three groups: a control group,
      a group exposed to lead with an additional calcium source (i.e. grit) and a group
      exposed to lead without access to an extra calcium source. Lead was administered
      as lead acetate via the drinking water (20 ppm) for 38 consecutive days. Exposure
      to lead increased significantly the concentrations of lead in kidney and bone in
      individuals of the experimental groups. Furthermore, the lack of a calcium
      supplement significantly enhanced the uptake of lead. Lead did not affect health
      indices such as hematocrit, spleen mass and body mass, nor the adrenal stress
      response. Cell-mediated immune responsiveness, assessed by a delayed-type
      hypersensitivity response to phytohaemagglutinin, was also not affected by lead
      exposure. On the other hand, lead exposure did significantly suppress the
      secondary humoral immune response towards sheep red blood cells in females, but
      only when the additional calcium source was not available. This effect was not
      found in males, suggesting sexual differences in susceptibility of humoral
      immunity to lead treatment in zebra finches.

PMID- 15572231
TI  - In situ exposures using caged organisms: a multi-compartment approach to detect
      aquatic toxicity and bioaccumulation.
AB  - An in situ toxicity and bioaccumulation assessment approach is described to
      assess stressor exposure and effects in surface waters (low and high flow), the
      sediment-water interface, surficial sediments and pore waters (including
      groundwater upwellings). This approach can be used for exposing species,
      representing major functional and taxonomic groups. Pimephales promelas, Daphnia
      magna, Ceriodaphnia dubia, Hyalella azteca, Hyalella sp., Chironomus tentans,
      Lumbriculus variegatus, Hydra attenuatta, Hexagenia sp. and Baetis tibialis were
      successfully used to measure effects on survival, growth, feeding, and/or uptake.
      Stressors identified included chemical toxicants, suspended solids, photo-induced
      toxicity, indigenous predators, and flow. Responses varied between laboratory and
      in situ exposures in many cases and were attributed to differing exposure
      dynamics and sample-processing artifacts. These in situ exposure approaches
      provide unique assessment information that is complementary to traditional
      laboratory-based toxicity and bioaccumulation testing and reduce the
      uncertainties of extrapolating from the laboratory to field responses.

PMID- 15572232
TI  - Using plant biomonitors and flux modelling to develop O3 dose-response
      relationships in Catalonia.
AB  - We used tobacco Bel-W3 biomonitoring data and ozone flux modelling (WINDEP model)
      with the aim of developing the absorbed dose-response relationship, and comparing
      this approach with the most commonly used AOT40 (the sum of hourly ozone
      concentrations above a cut-off of 40 ppb during daylight hours, when global
      radiation exceeds 50 W m(-2)) in the estimation of exposure-damage curves. Leaf
      damage values were more related to OAD(15 days, potential) (potential ozone
      absorbed dose calculated over 15 consecutive days) than to AOT40 in all the
      studied stations. An OAD(15 days, potential) of 180 mg m(-2) was found to be the
      threshold for damage to the most sensitive species in this region under well
      watered conditions. The results show the applicability of the flux approach for
      risk assessment at the local scale, the improvement of the ozone damage
      estimation when the potential absorbed dose is modelled and used instead of just
      the ozone exposure, and finally, the possibilities opened by the use of
      biomonitoring networks.

PMID- 15572233
TI  - The maximum reservoir capacity of soils for persistent organic pollutants:
      implications for global cycling.
AB  - The concept of maximum reservoir capacity (MRC), the ratio of the capacities of
      the surface soil and of the atmospheric mixed layer (AML) to hold chemical under
      equilibrium conditions, is applied to selected persistent organic pollutants
      (POPs) in the surface 'skin' (1 mm) of soils. MRC is calculated as a function of
      soil organic matter (SOM) content and temperature-dependent K(OA) and mapped
      globally for selected PCB congeners (PCB-28; -153; -180) and HCB, to identify
      regions with a higher tendency to retain POPs. It is shown to vary over many
      orders of magnitude, between compounds, locations and time
      (seasonally/diurnally). The MRC approach emphasises the very large capacity of
      soils as a storage compartment for POPs. The theoretical MRC concept is compared
      to reality and its implications for the global cycling of POPs are discussed.
      Sharp gradients in soil MRC can exist in mountainous areas and between the land
      and ocean. Exchanges between oceans and land masses via the atmosphere is likely
      to be an important driver to the global cycling of these compounds, and net ocean
      land transfers could occur in some areas.

PMID- 15572234
TI  - Water striders (family Gerridae): mercury sentinels in small freshwater
      ecosystems.
AB  - To circumvent some of the previous limitations associated with contaminant
      monitoring programs, we tested the suitability of the water strider (Hemiptera:
      Gerridae) as a mercury sentinel by comparing total mercury concentrations in
      water striders and brook trout (Salvelinus fontinalis) from a variety of stream
      sites in New Brunswick, Canada. There was a strong association between the two
      variables across sites (r(2)=0.81, P<0.001) in systems where both atmospheric
      deposition and a point source (an abandoned gold mine) were likely contributing
      to ambient mercury levels. In a small stream draining the gold mine tailings
      pile, water striders had mercury concentrations an order of magnitude higher than
      those from reference locations. Temporal variation at three southern New
      Brunswick stream sites was non-significant. These results suggest that water
      strider mercury levels accurately quantify food chain entry of the element. The
      use of sentinel species holds great potential for expanding contaminant
      monitoring programs.

PMID- 15572235
TI  - Mercury baseline levels in Flemish soils (Belgium).
AB  - It is important to establish contaminant levels that are normally present in
      soils to provide baseline data for pollution studies. Mercury is a toxic element
      of concern. This study was aimed at assessing baseline mercury levels in soils in
      Flanders. In a previous study, mercury contents in soils in Oost-Vlaanderen were
      found to be significantly above levels reported elsewhere. For the current study,
      observations were extended over two more provinces, West-Vlaanderen and
      Antwerpen. Ranges of soil Hg contents were distinctly higher in the province Oost
      Vlaanderen (interquartile range from 0.09 to 0.43 mg/kg) than in the other
      provinces (interquartile ranges from 0.7 to 0.13 and 0.7 to 0.15 mg/kg for West
      Vlaanderen and Antwerpen, respectively). The standard threshold method was
      applied to separate soils containing baseline levels of Hg from the data.
      Baseline concentrations for Hg were characterised by a median of 0.10mg Hg/kg dry
      soil, an interquartile range from 0.07 to 0.14 mg/kg and a 90% percentile value
      of 0.30 mg/kg. The influence of soil properties such as clay and organic carbon
      contents, and pH on baseline Hg concentrations was not important. Maps of the
      spatial distribution of Hg levels showed that the province Oost-Vlaanderen
      exhibited zones with systematically higher Hg soil contents. This may be related
      to the former presence of many small-scale industries employing mercury in that
      region.

PMID- 15572237
TI  - John D. Ferry's patents.

PMID- 15572238
TI  - Crystallization kinetics of homopolymers: overall crystallization: a review.
AB  - This paper is a brief review of the overall crystallization kinetics of synthetic
      homopolymers. The basic experimental results are presented and compared with
      theory that is currently available. It is found, surprisingly, that the more
      sophisticated theories do no better in explaining experimental results than does
      the free-growth approximation. This is contrary to what is observed for the
      crystallization of low molecular weight substances. The reason can be attributed
      to entanglements and other topological defects that are present in the pure melt
      and are relegated to the non-crystalline regions as crystallization progresses.
      This results in a more protracted crystallization than is predicted and is yet to
      be included in theory.

PMID- 15572239
TI  - The thrombin-fibrinogen interaction.
AB  - The thrombin-catalyzed conversion of fibrinogen (F) to fibrin consists of three
      reversible steps, with thrombin (T) being involved in only the first step which
      is a limited proteolysis to release fibrinopeptides (FpA and FpB) from fibrinogen
      to produce fibrin monomer. In the second step, fibrin monomers form intermediate
      polymers through noncovalent interactions. In the third step, the intermediate
      polymers aggregate to form the fibrin clot. The molecular mechanisms of the first
      two steps are elucidated.

PMID- 15572240
TI  - Review of some unusual effects of calcium binding to fibrinogen.
AB  - Calcium binding curves of human and bovine fibrinogen were obtained by using a
      calcium sensitive electrode. The two were identical and showed 2 high, 2-3 medium
      and more than 15 low affinity sites. Differential scanning calorimetry at neutral
      pH demonstrated the presence of the D and E domains of fibrinogen; however, at pH
      3.5 the D-domain was split into two. The presence of the subdomains was
      demonstrated also by digestion by pepsin at this pH. Combination of digestion of
      fibrinogen and of its fragments with different enzymes and temperatures
      identified up to 12 subdomains in the original molecule. Clotting of fibrinogen
      by thrombin at pH 7.0 was investigated also by differential scanning calorimetry.
      In the absence of Ca2+ clotting elicited a 40% increase in the enthalpy of
      thermal denaturation of the D domain of fibrinogen, but the position of the peak
      increased only by 0.4 degrees C. However, with clotting in the presence of 10(-3)
      M calcium the former increased by 70-75% and the latter by 11.0 degrees C, while
      these parameters of the E-domain remained unchanged. Changes of bound calcium
      during clotting were also measured with the calcium sensitive electrode. These
      had to be corrected, because the drop in free calcium was partly compensated by
      release of some calcium that was already bound to fibrinogen. Log of the half
      time of calcium uptake plotted against log thrombin concentration indicated a
      first order process with respect to thrombin concentration, moreover, the rate
      determined corresponded to that of the conformation change measured by
      calorimetry. The calcium uptake was correlated with release of the
      fibrinopeptides. Release of fibrinopeptide B follows parallel to binding of
      calcium and that of fibrinopeptide A is about fourfold faster. Polymerization and
      formation of thick bundles of fibrin is connected with release of fibrinopeptide
      A. Clotting with Ancrod, an enzyme that releases only fibrinopeptide A, showed
      only minimal binding of calcium. The polymerization inhibiting tetrapeptide Gly
      Pro-Arg-Pro also depressed binding of calcium. These data suggest that a calcium
      binding site must be in the proximity of the site of release of fibrinopeptide B
      and of a polymerization site.

PMID- 15572241
TI  - Deciphering the physiological pathway of clotting of fibrinogen in blood plasma.
AB  - I have been fortunate to have benefited over the years from the friendship and
      advice of John Ferry in our research to decipher the physiological reactions and
      regulatory events involved in the clotting of fibrinogen in blood. The article is
      a tribute to the memory of this creative scientist and remarkable individual.

PMID- 15572242
TI  - Fibrinopeptides and fibrin gel structure.
AB  - The mechanisms involved in fibrin gel formation are reviewed. Furthermore, a new
      concept of the role of fibrinopeptide release in this process is presented.

PMID- 15572243
TI  - Quantitative analysis of aggregation in dilute solutions of effectively rigid
      biomacromolecules via the combination of oscillatory flow birefringence and
      viscoelasticity measurements: example study of aggregation of bovine fibrinogen
      in aqueous glycerol, and detection of a large aggregate formed on addition of
      guanidine hydrochloride.
AB  - Oscillatory flow birefringence (OFB) properties have been measured for dilute
      solutions of bovine fibrinogen in 65-68% aqueous glycerol with the Miller-Schrag
      Thin Fluid Layer (TFL) apparatus employing either titanium or stainless steel
      surfaces in contact with the solutions. The shearing frequency range was 1 to
      2500 Hz, the concentrations ranged from 4 to 8 mg/ml, and measurement
      temperatures were 9.9, 10.0, and 15.8 degrees C. The data showed evidence of
      significant amounts of aggregation that apparently is caused by the presence of
      glycerol; contributions from the various aggregates were readily detected since
      the staggered half-overlap aggregation in this system results in substantial
      differences in the rotational relaxation times of the various effectively rigid
      aggregates. The combination of oscillatory flow birefringence and viscoelasticity
      (VE) data provided sensitive and precise characterization of aggregation in these
      example systems; all aggregates exhibited the expected positive optical
      anisotropy. The length of unaggregated fibrinogen in solution was found to be
      that obtained via electron microscopy. Addition of guanidine hydrochloride to
      hopefully reduce aggregation did so but also resulted in formation of a very
      large (2800 to 3500 A), apparently nearly monodisperse, negatively birefringent
      aggregate, suggesting that this new species might be formed by lateral
      aggregation.

PMID- 15572244
TI  - Gibbs-Duhem-based relationships among derivatives expressing the concentration
      dependences of selected chemical potentials for a multicomponent system.
AB  - For a two-component system, a derivative that specifies the concentration
      dependence of one chemical potential can be calculated from the corresponding
      derivative of the other chemical potential by applying the Gibbs-Duhem Equation.
      To extend the practical utility of this binary thermodynamic linkage to systems
      having any number of components, we present a derivation based on a previously
      unrecognized recursive relationship. Thus, for each independently variable
      component, kappa, any derivative of its chemical potential, mukappa, with respect
      to one of the mole ratios {mkappa identical with nkappa/nomega} is related to as
      a characteristic series of progressively higher order derivatives of muomega for
      a single "probe" component, omega, with respect to certain of the {mkappa}. For
      aqueous solutions in which omega is solvent water and one or more of the solutes
      (kappa) is dilute, under typical conditions each sum of terms expressing a
      derivative of mukappa consists of at most a few numerically significant
      contributions, which can be quantified, or at least estimated, by analyzing
      osmometric data to determine how the single chemical potential muomega depends on
      the {mkappa} without neglecting any significant contributions from the other
      components. Expressions derived here also will provide explicit criteria for
      testing various approximations built into alternative analytic strategies for
      quantifying derivatives that specify the {mkappa} dependences of mukappa for
      selected components. Certain quotients of these derivatives are of particular
      interest in so far as they gauge important thermodynamic effects due to
      "preferential interactions".

PMID- 15572245
TI  - Some comments on John Ferry's most enduring paper.
AB  - In this brief memoir, I reflect on the great insight John Ferry exhibited in his
      extremely influential 1952 paper on the mechanism of fibrinogen being changed
      into fibrin.

PMID- 15572246
TI  - A physical model for a fibrous network and its application to the shear modulus
      and other data of the fibrin gel.
AB  - A physical model for a fibrous network is developed and used to calculate its
      shear modulus. The model is applied to the shear modulus data of the fibrin gel
      and compared with other data related to the fibrin gel to elucidate the physical
      origins for some of the interesting properties of the gel such as the
      concentration dependence of the shear modulus and the difference between fine and
      course gels.

PMID- 15572247
TI  - Studies on fibrin polymerization and fibrin structure--a retrospective.

PMID- 15572248
TI  - Elastic contributions dominate the viscoelastic properties of sputum from cystic
      fibrosis patients.
AB  - Sputum samples from cystic fibrosis (CF) patients were investigated by
      oscillatory, creep and steady shear rheological techniques over a range of time
      scales from 10(-3) to 10(6) s. The viscoelastic changes obtained by mixing sputa
      with the actin-filament-severing protein gelsolin and with the thiol-reducing
      agent dithiothreitol (DTT) were also investigated. At small strains sputum
      behaves like a viscoelastic solid rather than a liquid. A nearly constant steady
      shear viscosity at low shear rates is only observed after long shearing times
      which cause irreversible changes in the samples. Creep-recovery tests confirm
      that sputa exhibit viscoelastic properties, with a significant elastic recovery.
      The results suggest that measurements of elastic moduli, rather than viscosities
      are more closely related to the mechanical properties of sputum in situ. Severing
      of actin filaments lowers the elastic modulus by 30-40%, but maintains
      viscoelastic integrity, while reduction of thiols in the glycoproteins nearly
      completely fluidizes the samples.

PMID- 15572249
TI  - Actions of the functional upstream domain of protein F1 of Streptococcus pyogenes
      on the conformation of fibronectin.
AB  - Fibronectin (Fn), discovered by Harvard's Plasma Protein Program as plasma "cold
      insoluble globulin" in the 1940s, has attracted much interest over the past three
      decades. One of the most interesting features of Fn is its ability to change
      shape in response to various environmental conditions and interactions with other
      substances found in the extra-cellular space. Here we examine the potential of
      the functional upstream domain (FUD) of Streptococcus pyogenes protein F1 to
      bring about changes in structure of Fn. In particular, we investigate the
      accessibility of Fn's 10th type III module that contains the integrin binding RGD
      motif. By use of monoclonal antibodies in a competitive ELISA assay, we found
      that FUD interacts with the amino-terminal type I modules of Fn to unveil the
      cell-binding region of Fn. This conformational change was achieved at sub
      equimolar ratios of FUD/Fn monomer. We discuss the functional relevance of the
      interaction for both Fn and S. pyogenes and correlate the results with a
      conformational model of Fn that arose out of a collaboration between our
      laboratory and that of John Ferry.

PMID- 15572250
TI  - The ultrastructure of fibrinogen-420 and the fibrin-420 clot.
AB  - Fibrinogen-420 is a minor subclass of human fibrinogen that is so named because
      of its higher molecular weight compared to fibrinogen-340, the predominant form
      of circulating fibrinogen. Each of the two Aalpha chains of fibrinogen-340 is
      replaced in fibrinogen-420 by an Aalpha isoform termed alphaE. Such chains
      contain a globular C-terminal extension, alphaEC, that is homologous with the C
      terminal regions of Bbeta and gamma chains in the fibrin D domain. The alphaEC
      domain lacks a functional fibrin polymerization pocket like those found in the D
      domain, but it does contain a binding site for beta2 integrins. Electron
      microscopy of fibrinogen-340 molecules showed the major core fibrinogen domains,
      D-E-D, plus globular portions of the C-terminal alphaC domains. Fibrinogen-420
      molecules had two additional globular domains that were attributable to alphaEC.
      Turbidity measurements of thrombin-cleaved fibrinogen-420 revealed a reduced rate
      of fibrin polymerization and a lower maximum turbidity. Thromboelastographic
      measurements also showed a reduced rate of fibrin-420 polymerization (amplitude
      development) compared with fibrin-340. Nevertheless, the final amplitude (MA) and
      the calculated elastic modulus (G) for fibrin-420 were greater than those for
      fibrin-340. These results suggested a greater degree of fibrin-420 branching and
      thinner matrix fibers, and such structures were found in SEM images. In addition,
      fibrin-420 fibers were irregular and often showed nodular structures protruding
      from the fiber surface. These nodularities represented alphaEC domains, and
      possibly alphaC domains as well. TEM images of negatively shadowed fibrin-420
      networks showed irregular fiber borders, but the fibers possessed the same 22.5
      nm periodicity that characterizes all fibrin fibers. From this result, we
      conclude that fibrin-420 fiber assembly occurs through the same D-E interactions
      that drive the assembly of all fibrin fibrils, and therefore that the staggered
      overlapping molecular packing arrangement is the same in both types of fibrin.
      The alphaEC domains are arrayed on fiber surfaces, and in this location, they
      would very likely slow lateral fibril association, causing thinner, more branched
      fibers to form. However, their location on the fiber surface would facilitate
      cellular interactions through the integrin receptor binding site.

PMID- 15572251
TI  - John Ferry and the mechanical properties of cross-linked fibrin.
AB  - This article describes the role John Ferry played in relating the location of
      cross-linked gamma-chains in fibrin fibrils to the mechanical properties of
      fibrin clot.

PMID- 15572252
TI  - Zoetic polymers.
AB  - Conditions mediating the formation of biological polymers in situ are reviewed,
      and terminology suggested to differentiate polymers found in living cells from
      synthetic materials and polymers derived from biological sources that are
      modified or studied in a way that obscures their biological function. Methods
      currently used to characterize the mechanical properties of biopolymer networks
      in cells are briefly discussed.

PMID- 15572253
TI  - FXIII polymorphisms, fibrin clot structure and thrombotic risk.
AB  - Fibrin clot structure is highly dependent on factor XIII activity. Activated
      FXIII catalyzes the formation of the peptide bonds between the gamma and alpha
      chains in noncovalently bound fibrin polymers and incorporates various adhesive
      and antifibrinolytic proteins into the final fibrin clot. In the absence of
      activated FXIII, clots are unstable and susceptible to fibrinolysis. Several
      studies have examined the effects of FXIII polymorphisms on final fibrin clot
      structure and clinical thrombotic risk. The Val34Leu FXIII polymorphism is
      associated with increased activation by thrombin. In the presence of saturating
      thrombin concentrations, however, FXIIIa specific enzyme activity is not affected
      by genetic polymorphisms. Fibrin clots formed in the presence of the FXIII 34Leu
      polymorphisms do tend to be thinner and less porous, however. The effects of
      prothrombin concentrations on clot structure have suggested that thinner clots
      are more resistant to fibrinolysis and associated with increased thrombotic risk.
      Most clinical studies of 34Leu FXIII carriers, however, have demonstrated a lower
      incidence of both venous and arterial thrombosis in carriers of the mutant allele
      compared to Val/Val carriers. One recent study has suggested that the
      interactions between FXIII phenotype and plasma fibrinogen concentrations
      significantly influence clinical thrombotic risk.

PMID- 15572254
TI  - The phylogeny of persistence in DNA.
AB  - We continue our study, Poland [Biophysical Chemistry 110 (2004) 59-2], of the
      distribution of C or G (C-G for short) in the DNA of select organisms, in
      particular, the tendency for C-G to cluster on all scales with respect to the
      number of bases considered. We previously found that if we counted the number of
      C-G bases in consecutive, nonoverlapping boxes containing a total of m bases,
      then the width of the distribution function describing how many C-G bases are in
      a box increases with respect to m dramatically relative to the width expected for
      a random distribution. The relative width of the C-G composition distribution
      function was found to vary accurately as a power law with respect to m, the size
      of the box, over a very wide range of m values. We express the power law in terms
      of a characteristic exponent gamma, that is, the relative widths of the
      distributions vary as m(gamma). The enhanced relative width of the distribution
      functions is a direct consequence of the tendency for boxes of similar
      composition to follow one another. This tendency represents persistence in
      composition from box to box and hence we refer to gamma as the persistence
      exponent. The occurrence of a power law means that the tendency for C-G to
      cluster is present on all scales of sequence length (box size) up to the total
      length of the chromosome which for bacteria is the entire genome. The persistence
      exponent gamma that characterizes the power law is thus an important parameter
      describing the distribution of C-G on all scales from individual base pairs up to
      the total length of the DNA sample considered. In the present paper, we determine
      the characteristic exponent gamma and the associated fractal dimension of DNA
      samples for a selection of species representing all of the major types of
      organism, that is, we explore the phylogeny of the exponent gamma. Here we treat
      six prokaryotes and six eukaryotes which, together with the species we have
      previously treated, brings the total number of species we have examined to 15. We
      find the power law form for the C-G distribution for all of the species treated
      and hence this behavior seems to be ubiquitous. The values of the characteristic
      exponent gamma that we find tend to cluster around the value gamma=0.20 with no
      obvious pattern with respect to phylogeny. The extreme values that we obtain are
      gamma=0.057 (yeast) and gamma=0.386 (human). We conclude by showing that the
      persistence of C-G clustering on the scale of the length of a chromosome is
      dramatically illustrated by interpreting the C-G distribution as a random walk.

PMID- 15572255
TI  - Anionic regulation of biological systems: the special role of chloride in the
      coagulation cascade.
AB  - The discovery that previously unidentified allosteric properties of several
      proteins, such as fibrinogen and myoglobin, can be triggered by anions binding,
      has suggested the possibility to design a new "active" role of chloride in the
      modulation of a broad range of biological systems. The molecular bases of the
      anions binding to proteins depends by their charge density in turn regulating the
      ability to bind water molecules and interact with basic groups on proteins. This
      review reports the role of the physiologically relevant chloride, and of other
      anions, in the regulation of several proteins, with special attention to the
      coagulation cascade. Moreover, possible mechanisms of modification of plasma,
      intra- or extracellular chloride concentration are listed.

PMID- 15572256
TI  - Crystal structure of the thrombin mutant D221A/D222K: the Asp222:Arg187 ion-pair
      stabilizes the fast form.
AB  - The thrombin mutant D221A/D222K (ARK) does not bind Na+ and has interesting
      functional properties intermediate between those of the slow and fast forms of
      wild type. We solved the X-ray crystal structure of ARK bound at exosite I with a
      fragment of hirudin at 2.4-A resolution. The structure shows a slight collapse of
      the 186 and 220 loops into the Na+ binding site due to disruption of the
      Asp222:Arg187 ion-pair. The backbone O atoms of Arg221a and Lys224 are shifted
      into conformations that eliminate optimal interaction with Na+. A paucity of
      solvent molecules in the Na+ binding site is also noted, by analogy to what is
      seen in the structure of the slow form. These findings reinforce the crucial role
      of the Asp222:Arg187 ion-pair in stabilizing the fast form of thrombin.

PMID- 15572257
TI  - Do the isolated fibrinogen alphaC-domains form ordered oligomers?
AB  - Previous electron microscopy (EM) studies revealed that the proteolytically
      prepared, truncated, bovine fibrinogen alphaC-domain (Aalpha223-539 fragment)
      upon transfer from acidic to neutral pH formed ordered oligomers which could
      mimic alpha polymers of cross-linked fibrin. In this study, we demonstrated that
      although its recombinant analog, bAalpha224-538, as well as the full-length
      version of the alphaC-domain (bAalpha224-568), upon similar treatment also formed
      oligomers with ordered structure, both were monomeric when kept in neutral pH
      buffer. To search further for conditions for their oligomerization, we treated
      bAalpha224-568 with factor XIIIa, purified the cross-linked soluble fraction, and
      confirmed that it consisted of oligomers. Similar cross-linked oligomers were
      obtained with the recombinant human alphaC-domain (residues Aalpha221-610). In a
      cell adhesion assay, the adhesion of human umbilical vein endothelial cells
      (HUVEC) to the alphaC-domains substantially increased upon oligomerization. These
      results demonstrate that the recombinant alphaC-domains can form stable oligomers
      which may mimic properties of the alphaC-domains in cross-linked fibrin.

PMID- 15572258
TI  - The mechanical properties of fibrin for basic scientists and clinicians.
AB  - In this review, I set forth some basic information about the mechanical
      properties of fibrin clots and attempt to identify the big questions remaining.
      The intent is to make this topic understandable to both basic scientists who are
      interested in blood clotting and to hematologists or cardiologists, since I
      believe that this is something everyone working in these fields should know. The
      viscoelastic properties of fibrin are remarkable and unique among polymers.
      Moreover, these properties are essential to the physiology of blood clotting and
      are important for understanding and therefore preventing and treating thrombosis.

PMID- 15572259
TI  - Modes and consequences of thrombin's interaction with fibrin.
AB  - Thrombin mediates the balance between coagulant and fibrinolytic forces and has
      numerous cellular effects. This intricate balance is maintained by biochemical
      mechanisms that regulate thrombin activity. Disruption of this balance could lead
      to bleeding or thrombosis. Once thrombin is generated, two major mechanisms
      regulate its activity. By binding fibrin, thrombin's activity is localized to the
      thrombus, a process that limits its systemic procoagulant effects. Thrombin that
      escapes into the circulation is efficiently inactivated by plasma inhibitors,
      such as antithrombin, or is sequestered by thrombomodulin on the endothelium.
      Although thrombin's interaction with fibrin limits its systemic effects, fibrin
      bound thrombin resists inactivation and can produce a local procoagulant stimulus
      that triggers thrombus growth. Direct thrombin inhibitors were developed, at
      least in part, to target fibrin-bound thrombin. These agents are finding their
      niche for the prevention and treatment of venous and arterial thrombosis. The
      mechanisms by which thrombin binds fibrin are reviewed in this paper. As well,
      the potential pathological consequences of thrombin's interaction with fibrin are
      discussed.

PMID- 15572260
TI  - Aspartame and aspartame derivatives effect human thrombin catalytic activity.
AB  - The study of small Asp-Phe analogs was undertaken since this dipeptide sequence
      is critical in fibrinogen recognition and catalysis. The inhibition of clotting
      activity by Asp-Phe-methyl ester (aspartame), formyl-Asp-Phe-methyl ester and
      acetyl-Asp-Phe was biphasic in all cases, indicating the presence of at least two
      binding sites. The N-terminally blocked derivatives are stronger inhibitors than
      aspartame. In contrast, tosyl-Gly-Pro-Arg-p'-nitroanilide hydrolysis was
      inhibited minimally by Asp-Phe-methyl, ester [Ki(app)=98 mM]. Acetyl-Asp-Phe
      inhibition of thrombin amidase activity was biphasic, tenfold stronger and
      appeared to be strongly cooperative. These results are discussed with respect to
      the inhibition of alpha-thrombin by ATP.

PMID- 15572262
TI  - Tools for measuring clinical effectiveness.
AB  - Efficacy studies fail to consider the multiple aspects of schizophrenia that
      determine the overall clinical effectiveness of treatment. We address this
      shortcoming by proposing definitions of six schizophrenia outcome domains which
      we believe contribute to clinical effectiveness: symptoms of disease,
      tolerability, everyday functioning, subjective well-being, family/career burden,
      and treatment adherence. Numerous specialised rating scales are in widespread
      use; however, these only assess specific aspects of schizophrenia within
      individual domains and are of limited use for measuring clinical effectiveness.
      New rating instruments that measure treatment outcomes across all six domains of
      schizophrenia need to be developed. One such scale is the revised Global Outcome
      Assessment of Life in Schizophrenia (GOALS) scale. We propose that further
      development of this scale should include validation in long-term studies,
      incorporation of the patient perspective of treatment within assessments, and
      education of clinicians on how to score this scale. If this approach to
      evaluating treatment outcomes is adopted, clinicians will be better placed to
      differentiate therapeutic interventions on the basis of clinical effectiveness.

PMID- 15572263
TI  - Clinical effectiveness in first-episode patients.
AB  - Managing patients with first-episode schizophrenia is a challenging task for
      psychiatrists. Early diagnosis and effective intervention are vital to achieving
      long-term positive clinical outcomes among first-episode patients. Although these
      patients are the most responsive to treatment, they are also more susceptible to
      adverse events. The efficacy and improved tolerability associated with the newer
      atypical antipsychotics means that these drugs can be used successfully in the
      treatment and long-term management of schizophrenia from the onset of illness.
      However, as well as managing the symptoms of the disease, pharmacological
      treatments need to meet the broader requirements of clinical effectiveness that
      encompass all of the outcome domains associated with schizophrenia. This article
      will discuss available data on atypical antipsychotics in first-episode patients
      and present the primary results from the F1RST (Southwark first-onset psychosis)
      study, which examined the use of quetiapine for the first-line management of
      schizophrenia as part of a specialist episode psychosis service.

PMID- 15572264
TI  - Clinical effectiveness in adults with chronic schizophrenia.
AB  - Schizophrenia is a severe, debilitating mental illness characterised by a
      progressive decline of the patient's functioning and relationship with the
      outside world. Although some patients recover, the illness more usually follows a
      chronic relapsing course. The long-standing nature of the illness gives rise to a
      variety of issues, such as poor general health and non-adherence to treatment,
      which can have a significant impact on the clinical effectiveness of
      antipsychotic therapy. It is therefore important that clinicians consider the
      wider aspects of clinical effectiveness, such as functional recovery, individual
      well-being, treatment adherence and patient satisfaction, when assessing the
      clinical effectiveness of antipsychotic therapy. Of the atypical antipsychotics
      currently available to treat chronic schizophrenia, clinical experience and
      results from clinical trials suggest that quetiapine can provide a broad range of
      symptomatic relief with minimal clinically significant adverse events. This, in
      turn, may lead to greater patient satisfaction, increased adherence and an
      improved treatment outcome. As with all atypical antipsychotics, the key to
      clinical effectiveness is appropriate dosing. Data from recent studies suggest
      that an appropriate target dose for quetiapine for many adults with schizophrenia
      is 600 mg/day.

PMID- 15572265
TI  - Clinical effectiveness of atypical antipsychotics in elderly patients with
      psychosis.
AB  - The elderly represent a unique patient group in the sense that they have a high
      prevalence of psychotic symptoms that are a manifestation of a variety of
      psychiatric, neurological and organic disorders. Treatment is complicated by
      several factors including comorbid diagnoses (psychiatric and medical),
      polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics and
      high susceptibility to adverse events. Elderly patients require pharmacological
      interventions that are effective in reducing symptoms but also are well
      tolerated, improve everyday functioning, subjective well-being and treatment
      adherence and reduce family/career burden. The ability of an antipsychotic to
      fulfil these requirements determines its clinical effectiveness. To date, few
      studies have investigated the clinical effectiveness of atypical antipsychotics
      in elderly patients. However, clear differences exist between the available
      agents, particularly with regard to tolerability profiles, which have a major
      impact on the clinical outcome of patients. Clinicians should select an agent
      that is not only effective in reducing psychotic symptoms but, more importantly,
      one that has a low incidence of adverse events, such as extrapyramidal symptoms
      (EPS) and neurocognitive problems, which are of concern in the elderly.

PMID- 15572266
TI  - Clinical effectiveness of new generation antipsychotics in adolescent patients.
AB  - In addition to management of symptoms of disease, pharmacological interventions
      in adolescents with psychotic disorders must be clinically effective to provide
      the best possible outcome in terms of well-being, functioning, and disease
      burden. Six outcome domains should be considered: symptoms of disease,
      tolerability, everyday functioning, subjective well-being, family/career burden,
      and treatment adherence. To date, few studies have compared the clinical
      effectiveness of the different new generation antipsychotics in adolescents.
      However, clear differences exist between available agents, particularly in terms
      of tolerability profile. This review will focus on the particular issues that
      clinicians need to consider in order to maximise the clinical effectiveness of
      the new generation antipsychotics in adolescent patients with psychosis. For
      example, adolescents are not only more susceptible to the side effects of
      antipsychotic medication than adults, but they are also more likely to be
      sensitive to the negative impact of side effects on appearance, body image, and
      self-esteem. Data available in children and adolescents will be reviewed, and the
      practical implications for patient management will be highlighted. The importance
      of dosing the new generation antipsychotics appropriately will also be discussed.

PMID- 15572268
TI  - Low GSK-3beta in schizophrenia as a consequence of neurodevelopmental insult.
AB  - Glycogen synthase kinase-3 (GSK-3) is a protein kinase highly abundant in brain
      and involved in signal transduction cascades, particularly neurodevelopment. Its
      activity and protein levels have been reported to be over 40% lower in postmortem
      frontal cortex of schizophrenic patients. GSK-3beta in occipital cortex of
      schizophrenic patients was not reduced, suggesting regional specificity. There
      was no reduction in GSK-3beta protein levels in fresh and immortalized
      lymphocytes and both GSK-3 activity and GSK-3beta mRNA levels in fresh
      lymphocytes from schizophrenic patients. In the schizophrenia-related neonatal
      ventral hippocampal lesion rat model, we measured GSK-3beta protein levels and
      GSK-3 activity in the frontal cortex. GSK-3beta protein levels in lesioned rats
      were significantly lower than in sham rats, favoring perinatal insult as a cause
      of low GSK-3beta in schizophrenia. Taken together, these studies suggest that low
      GSK-3 in postmortem brain of schizophrenic patients is a late consequence of
      perinatal neurodevelopmental insult in schizophrenia. In rats, acute or chronic
      cold restraint stress did not change GSK-3beta protein levels. Chronic treatment
      of rats with lithium, valproate, haloperidol or clozapine did not change rat
      cortical GSK-3beta protein levels ex vivo, supporting the concept that low GSK
      3beta in schizophrenia is not secondary to stress or drug treatment. Our initial
      findings of low GSK-3beta protein levels in postmortem brain have been replicated
      by another group. Our own group has found additionally that GSK-3beta mRNA levels
      were 40% lower in postmortem dorsolateral prefrontal cortex (DLPFC) of
      schizophrenic patients, supporting our previous findings. Further studies will be
      aimed at determining whether nonspecific neonatal damage or only specific factors
      cause low GSK-3 as a late effect. We plan to study whether low GSK-3beta activity
      is associated with biochemical effects such as elevated beta-catenin levels.

PMID- 15572269
TI  - Amantadine for weight gain associated with olanzapine treatment.
AB  - Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar
      (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale
      (BPRS) total score < or =45]; treated with olanzapine for 1-24 months; and who
      had gained > or =5% of their initial body weight were examined to determine
      whether amantadine could attenuate weight gain or promote weight loss. Olanzapine
      (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300
      mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis
      of weight showed that weight change from baseline [last-observation-carried
      forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc
      group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean+/-S.D.: 
      0.19+/-4.58 versus 1.28+/-4.26 kg, P=0.045). Mean BPRS total score, positive
      subscale, and anxiety-depression scores improved comparably in both groups, and
      Montgomery-Asberg Depression Rating Scale (MADRS) total score improved in the
      Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated
      weight gain or promoted weight loss in some patients who had gained weight during
      olanzapine therapy.

PMID- 15572270
TI  - Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by
      rat mixed glial and microglial cell cultures.
AB  - The cytokines IL-1beta and IL-2 are released from activated glial cells in the
      central nervous system and they are able to enhance catecholaminergic
      neurotransmission. There is no data concerning influence of antipsychotics on
      glial cell activity. Antipsychotics reaching the brain act not only on neurons
      but probably also on glial cells. The aim of this study was to evaluate the
      effect of chlorpromazine and loxapine on release of IL-1beta and IL-2 by mixed
      glial and microglial cell cultures. Chlorpromazine in concentrations 2 and 20
      muM, and loxapine 0.2, 2 and 20 microM reduced IL-1beta secretion by LPS
      activated mixed glia cultures after 1 and 3 days of exposure. Chlorpromazine in
      concentrations of 0.2, 2 and 20 microM reduced the IL-2 secretion in mixed glial
      cultures after 3 days of exposure. Loxapine in concentrations of 0.2, 2 and 20
      microM reduced IL-2 secretion in mixed glia cultures after 1 and 3 days of
      exposure, and additionally loxapine decreased IL-1beta and IL-2 secretion in LPS
      induced microglia cultures in concentrations of 2, 10 and 20 muM. Quinpirole-a D2
      dopaminergic agonist increased LPS-induced IL-1beta and IL-2 secretion in mixed
      glia cultures only in the highest dose of 20 microM. These findings suggest the
      absence of functional dopamine receptors on cortical microglial cells. Mixed glia
      cultures deprived of microglia (by shaking and incubating with L-leucine methyl
      ester) did not release IL-1beta and IL-2. This observation suggests that
      microglia can be a source of assessed cytokines. Results of the present study
      support the view that antipsychotics act not only on neurons but also on glial
      cells. However, the clinical significance of these observations still remains
      unclear.

PMID- 15572271
TI  - Endogenous cannabinoids are not involved in cocaine reinforcement and development
      of cocaine-induced behavioural sensitization.
AB  - The endogenous cannabinoid system is a relatively novel discovered system
      consisting of cannabinoid CB1 receptors, which are expressed both in the
      periphery and in the central nervous system, peripheral cannabinoid CB2 receptors
      and endogenous cannabinoids, which are anandamide and 2-arachidonyl glycerol. The
      cannabinoid CB1 receptors have recently been implicated in rewarding aspects of
      not only the cannabinoid drug Delta9-tetrahydrocannabinol (Delta9-THC), but also
      of other drugs of abuse, including cocaine. The present study was designed to
      further investigate the role of CB1 receptors in reward-related effects of
      cocaine. Using the CB1 receptor selective antagonist SR141716A, the involvement
      of CB1 receptors in cocaine reinforcement was determined by intravenous cocaine
      self-administration. In addition, the effects of the CB1 receptor selective
      antagonist SR141716A upon the development of cocaine-induced behavioural
      sensitization were investigated. SR141716A did not affect cocaine reinforcement
      nor did it affect the development of behavioural sensitization to the locomotor
      stimulant effects of cocaine. These findings suggest that CB1 receptors are not
      involved in acute cocaine reinforcement nor in cocaine-induced behavioural
      sensitization.

PMID- 15572272
TI  - Actometry and Barnes Akathisia Rating Scale in neuroleptic-induced akathisia.
AB  - We evaluated Barnes Akathisia Rating Scale (BARS) and standardized lower limb
      actometry in quantifying neuroleptic-induced akathisia (NIA) in 99 schizophrenia
      patients. Both instruments discriminated well between NIA and non-NIA patients
      and they correlated weakly but significantly. BARS was superior to actometry in
      screening DSM-IV diagnosed NIA patients. The results of this methodological study
      provide BARS with objective validation through movement measuring, that it has
      been suggested to need.

PMID- 15572273
TI  - No association of clock gene T3111C polymorphism and affective disorders.
AB  - CLOCK was hypothesised to be related to susceptibility of affective disorders. To
      test subsamples of affectively disordered patients, we examined age of onset
      (AoO), numbers of episodes and melancholic type of clinical manifestation. Using
      PCR and RFLP, we investigated in patients with unipolar depression and bipolar
      disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders
      (n=102) compared to healthy controls (n=103). No differences were found either in
      genotype or allele frequency distributions of T3111C polymorphism between
      patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg
      Equilibrium (HWE) were detected either in patients, or healthy controls. Results
      suggest that there is no association between the T3111C SNP and affective
      disorders in general. Data of our sample replicate prior findings of Desan et al.
      [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of
      affective episodes did show some deviations in genotypes (p=0.0585).

PMID- 15572274
TI  - Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in
      MPTP-treated mice.
AB  - We examined the effects of perindopril on the dopaminergic system in mice after 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. The mice received
      four intraperitoneal injections of MPTP at 1-h intervals. Administration of
      perindopril showed dose-dependent neuroprotective effects against striatal
      dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      depletion 3 days after MPTP treatment. Our immunohistochemical study showed that
      MPTP can severe damage in tyrosine hydroxylase (TH)-immunoreactive neurons after
      MPTP treatment. The administration of perindopril significantly attenuated MPTP
      induced substantia nigra and striatal damage. The present study also showed that
      the immunoreactivity of parvalbumin (PV)- or neuronal nitric oxide synthase
      (nNOS)-positive cells in the substantia nigra was decreased 7 days after MPTP
      treatment, whereas no significant changes were observed in these cells of the
      striatum throughout the experiments. The administration of perindopril
      significantly attenuated MPTP-induced decrease of the PV- or nNOS
      immunoreactivity in the nigral cells. In double-labeled immunostaining with anti
      PV and anti-nNOS antibody, PV-immunoreactive cell bodies and fibers were not
      double-labeled for nNOS-immunoreactive cell bodies and fibers in both the
      striatum and substantia nigra after MPTP treatment. Furthermore, PV- or nNOS
      immunoreactive cell bodies and fibers in both the striatum and substantia nigra
      were not double-labeled for TH-immunoreactive cell bodies and fibers. These
      results demonstrate that the ACE inhibitor perindopril has a dose-dependent
      protective effect against MPTP-induced striatal dopamine, DOPAC and HVA depletion
      in mice. The present study also demonstrates that perindopril is effective
      against MPTP-induced degeneration of the nigral neurons and interneurons.
      Furthermore, our immunohistochemical study suggests that PV-immunoreactive cells
      and nNOS-immunoreactive cells are different interneurons in both the striatum and
      substantia nigra. Thus, our results provide further evidence that the ACE
      inhibitor perindopril may offer a novel therapeutic strategy for Parkinson's
      disease (PD).

PMID- 15572275
TI  - Low-dose risperidone augmentation of fluvoxamine treatment in obsessive
      compulsive disorder: a double-blind, placebo-controlled study.
AB  - According to previous data, the addition of risperidone in obsessive-compulsive
      patients refractory to serotonin reuptake inhibitors (SRIs) is shown to be a safe
      and effective treatment strategy. The aims of our study were to evaluate the
      efficacy of risperidone addition, in comparison to placebo, in fluvoxamine
      refractory obsessive-compulsive patients and to investigate whether risperidone
      could boost the efficacy of fluvoxamine in fluvoxamine-responder patients.
      Subjects were 45 obsessive-compulsive inpatients, consecutively recruited at the
      Department of Neurosciences at the San Raffaele Hospital, Milan. Thirty-nine
      patients completed the study. All patients received 12 weeks of a standardized
      open-label fluvoxamine monotherapy and then continued for 6 weeks with placebo or
      risperidone in a double-blind design. Results showed a significant effect of
      risperidone addition, at the end of the double-blind phase (18th week), only for
      fluvoxamine-refractory patients. Five patients on risperidone (50%) and two (20%)
      on placebo became responders, with a Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS) decrease > or =35%. Risperidone was generally well tolerated, except for a
      mild transient sedation and a mild increase in appetite. This preliminary study
      suggests that even very low (0.5 mg) risperidone doses are effective in OC
      patients who were nonresponders to a standardized treatment with fluvoxamine.

PMID- 15572276
TI  - Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo
      controlled trial followed by a 9-week double-blind trial of risperidone and
      haloperidol.
AB  - In a randomized, double-blind trial, patients with acute bipolar mania received 1
      6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks,
      followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients,
      154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The
      mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day
      of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day
      during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score
      reductions from baseline were significantly greater in patients receiving
      risperidone than placebo (p<0.001). Differences between risperidone and
      haloperidol on this efficacy measure were not significant. Further reductions in
      YMRS scores were seen in patients receiving risperidone or haloperidol during the
      subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal
      disorder and hyperkinesias, the most commonly reported adverse events with
      antipsychotic use, occurred less frequently with risperidone than haloperidol. We
      conclude that risperidone monotherapy was an effective and well-tolerated
      treatment for bipolar mania and that efficacy was maintained over the long term.

PMID- 15572277
TI  - Adenosine A1 receptors and the anticonvulsant potential of drugs effective in the
      model of 3-nitropropionic acid-induced seizures in mice.
AB  - The role of adenosine A1 receptors in the activity of drugs and substances
      protecting against seizures evoked by mitochondrial toxin, 3-nitropropionic acid
      (3-NPA) was studied in mice. Non-selective A1/A2 adenosine receptor antagonist,
      aminophylline and selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) diminished the anticonvulsive effects of diazepam,
      phenobarbital, valproate and gabapentin. In contrast, A1/A2 adenosine receptor
      antagonist, 8-(p-sulfophenyl)theophylline (8pSPT) not penetrating via blood-brain
      barrier was ineffective. Aminophylline and DPCPX but not 8pSPT also reversed the
      protective action of A1/A2 adenosine receptor agonist, 2-chloroadenosine (2-CADO)
      and selective A1 adenosine receptor agonist, R-N6-phenylisopropyloadenosine (R
      PIA), against 3-NPA-evoked convulsions. Obtained results suggest that the central
      adenosine A1 receptor stimulation may play a role in the anticonvulsive potential
      of diazepam, phenobarbital, valproate and gabapentin in a novel model of 3-NPA
      evoked seizures. Moreover, concomitant application of aminophylline with these
      drugs may reduce their clinical antiepileptic efficacy, especially among patients
      suffering from seizures related to the disturbances of mitochondrial respiratory
      chain.

PMID- 15572278
TI  - The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine
      transporter density in Korean children with attention deficit hyperactivity
      disorder: relating to treatment response to methylphenidate.
AB  - The symptoms of attention deficit hyperactivity disorder (ADHD) can be treated
      with methylphenidate (MPH), a potent blocker of dopamine transporter (DAT). The
      homozygosity of the 10-repeat allele at the DAT gene (DAT1) seems to be
      associated with a poor response to MPH in children with ADHD. In the present
      study, we investigated the association between DAT density using I-123-N-(3
      iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane [123I]IPT
      single photon emission computed tomography (SPECT)] and the homozygosity for 10
      repeat allele at DAT1 and response to MPH in Korean children with ADHD. Eleven
      drug-naive children with ADHD were included in the study and treated with MPH for
      about 8 weeks. After the genotyping and SPECT were performed, we compared DAT
      density between ADHD children with and without the homozygosity for 10-repeat
      allele at DAT1 and investigated the correlation between the homozygosity for 10
      repeat allele and response to MPH. ADHD children with 10/10 genotype (n=7) had a
      significantly greater increase of the DAT density in basal ganglia than the
      children without 10/10 genotype (n=4). We found that while only 28.6% (2/7) of
      the subject with 10/10 genotype showed good response to MPH treatment, 100% (4/4)
      of the subjects without 10/10 genotype showed good response to MPH treatment. Our
      findings support an association between homozygosity for 10-repeat allele at DAT1
      and the DAT density assessed in vivo and correlation between the homozygosity for
      10-repeat allele and poor response to MPH.

PMID- 15572279
TI  - Inhibition of rat liver CYP2D in vitro and after 1-day and long-term exposure to
      neuroleptics in vivo-possible involvement of different mechanisms.
AB  - The aim of the present study was to investigate the influence of classic and
      atypical neuroleptics on the activity of rat CYP2D measured as a rate of
      ethylmorphine O-deethylation. The reaction was studied in control liver
      microsomes in the presence of neuroleptics, as well as in microsomes of rats
      treated intraperitoneally (i.p.) for 1-day or 2-weeks (twice a day) with
      pharmacological doses of the drugs (promazine, levomepromazine, thioridazine,
      perazine 10 mg kg(-1); chlorpromazine 3 mg kg(-1); haloperidol 0.3 mg kg(-1);
      risperidone 0.1 mg kg(-1); sertindole 0.05 mg kg(-1)), in the absence of the
      neuroleptics in vitro. Neuroleptics added in vitro to control liver microsomes
      decreased the activity of the rat CYP2D by competitive or mixed inhibition of the
      enzyme. Thioridazine (Ki=15 microM) was the most potent inhibitor of the rat
      CYP2D among the drugs studied, whose effect was more pronounced than that of the
      other neuroleptics tested: phenothiazines (Ki=18-23 microM), haloperidol (Ki=32
      microM), sertindole (Ki=51 microM) or risperidone (Ki=165 microM). The
      investigated neuroleptics-when given to rats in vivo-also seemed to exert an
      inhibitory effect on CYP2D via other mechanisms. One-day exposure of rats to the
      classic neuroleptics decreased the activity of CYP2D in rat liver microsomes.
      After chronic treatment with the investigated neuroleptics, the decreased CYP2D
      activity produced by the phenothiazines was still maintained, while that caused
      by haloperidol diminished. Moreover, risperidone decreased the activity of that
      enzyme. The obtained results indicate drug- and time-dependent interactions
      between the investigated neuroleptics and the CYP2D subfamily of rat cytochrome P
      450, which may proceed via different mechanisms: (1) competitive or mixed
      inhibition of CYP2D shown in vitro, the inhibitory effects of phenothiazines
      being stronger than those of haloperidol or atypical neuroleptics, but weaker
      than the effects of the respective drugs on human CYP2D6; (2) in vivo inhibition
      of CYP2D, produced by both 1-day and chronic treatment with phenothiazines, which
      suggests inactivation of enzyme by intermediate metabolites; (3) in vivo
      inhibition of CYP2D by risperidone, produced only by chronic treatment with the
      drug, which suggests its influence on the enzyme regulation.

PMID- 15572280
TI  - Comparative efficacy and safety of long-acting risperidone and risperidone oral
      tablets.
AB  - A double-blind study of long-acting injectable risperidone and oral risperidone
      tablets was conducted in 640 patients with schizophrenia. All patients received
      flexible doses of 1-6 mg of oral risperidone for 8 weeks. Doses were stable
      during weeks 5-8. At the end of week 8, symptomatically stable patients were
      randomly assigned to receive long-acting risperidone (active injections, dummy
      oral) or continued oral risperidone (dummy injections, active oral) for 12 weeks.
      Significant improvements were demonstrated from baseline to endpoint in Positive
      and Negative Syndrome Scale (PANSS) total (P<0.001) and factor scores (P<0.05) in
      both groups. According to a noninferiority analysis, the two treatments showed
      comparable efficacy in total PANSS scores over the short-term. No unexpected
      adverse events were recorded. The findings indicate that symptomatically stable
      patients can be safely switched from oral risperidone to long-acting injectable
      risperidone without compromising efficacy.

PMID- 15572281
TI  - Antidepressants attenuate both the enhanced ethanol intake and ethanol-induced
      anxiolytic effects in diazepam withdrawn rats.
AB  - We have recently shown that the abrupt discontinuation of chronic diazepam (DZM)
      administration facilitated ethanol consumption and enhanced the anxiolytic
      properties of ethanol. Tricyclic antidepressants such as desipramine and the
      selective serotonin reuptake inhibitor fluoxetine have been shown to reduce
      alcohol intake in rodent models of alcoholism and in alcoholics who are
      depressed. In the present study, we tested whether desipramine (1.25; 2.5 and 5
      mg/kg, i.p.) and fluoxetine (5 mg/kg, i.p.) treatment affect both ethanol intake
      in a free-choice test and the anxiolytic effect induced by ethanol in DZM
      withdrawn rats. Adult male Wistar rats were submitted to a chronic DZM treatment
      (2 mg/kg per day) or vehicle (VEH) for 21 days. Twenty-four hours after the last
      DZM injection, rats were subjected to a free-choice paradigm between water and
      increasing ethanol concentrations with or without concurrent desipramine or
      fluoxetine administration (ethanol concentration (v/v) was increased every 4 days
      as follows: 2, 4, 6, 8 and 10% for the final 8 days). Chronic treatment with
      desipramine (24 days, twice a day, 2.5 and 5 mg/kg, i.p.) and fluoxetine (24
      days, once a day; 5 mg/kg, i.p.) significantly reduced the amount of ethanol
      intake in DZM withdrawn rats. Furthermore, subchronic treatments with desipramine
      (4 days, twice a day, 2.5 and 5 mg/kg) and fluoxetine (4 days, once a day, 5
      mg/kg, i.p.) blocked the anxiolytic-like behavior in the elevated plus maze
      induced by ethanol (1 g/kg; i.p.) in DZM withdrawn rats at day 5 of withdrawal.
      The present findings suggest that desipramine and fluoxetine could be effective
      pharmacological tools to prevent the subsequent development of ethanol dependence
      in rats previously exposed to DZM withdrawal.

PMID- 15572284
TI  - Mutagens in surface waters: a review.
AB  - A review of the literature on the mutagenicity/genotoxicity of surface waters is
      presented in this article. Subheadings of this article include a description of
      sample concentration methods, mutagenic/genotoxic bioassay data, and suspected or
      identified mutagens in surface waters published in the literature since 1990.
      Much of the published surface water mutagenicity/genotoxicity studies employed
      the Salmonella/mutagenicity test with strains TA98 and/or TA100 with and/or
      without metabolic activation. Among all data analyzed, the percentage of positive
      samples toward TA98 was approximately 15%, both in the absence and the presence
      of S9 mix. Those positive toward TA100 were 7%, both with and without S9 mix. The
      percentage classified as highly mutagenic (2500-5000 revertants per liter) or
      extremely mutagenic (more than 5000 revertants per liter) was approximately 3-5%
      both towards TA98 and TA100, regardless of the absence or the presence of S9 mix.
      This analysis demonstrates that some rivers in the world, especially in Europe,
      Asia and South America, are contaminated with potent direct-acting and indirect
      acting frameshift-type and base substitution-type mutagens. These rivers are
      reported to be contaminated by either partially treated or untreated discharges
      from chemical industries, petrochemical industries, oil refineries, oil spills,
      rolling steel mills, untreated domestic sludges and pesticides runoff. Aquatic
      organisms such as teleosts and bivalves have also been used as sentinels to
      monitor contamination of surface water with genotoxic chemicals. DNA
      modifications were analyzed for this purpose. Many studies indicate that the 32P
      postlabeling assay, the single cell gel electrophoresis (comet) assay and the
      micronucleus test are sensitive enough to monitor genotoxic responses of
      indigenous aquatic organisms to environmental pollution. In order to efficiently
      assess the presence of mutagens in the water, in addition to the chemical
      analysis, mutagenicity/genotoxicity assays should be included as additional
      parameters in water quality monitoring programs. This is because according to
      this review they proved to be sensitive and reliable tools in the detection of
      mutagenic activity in aquatic environment. Many attempts to identify the
      chemicals responsible for the mutagenicity/genotoxicity of surface waters have
      been reported. Among these reports, researchers identified heavy metals, PAHs,
      heterocyclic amines, pesticides and so on. By combining the blue cotton hanging
      method as an adsorbent and the O-acetyltransferase-overproducing strain as a
      sensitive strain for aminoarenes, Japanese researchers identified two new type of
      potent frameshift-type mutagens, formed unintentionally, in several surface
      waters. One group has a 2-phenylbenzotriazole (PBTA) structure, and seven
      analogues, PBTA-type mutagens, were identified in surface waters collected at
      sites below textile dyeing factories and municipal wastewater treatment plants
      treating domestic wastes and effluents. The other one has a polychlorinated
      biphenyl (PCB) skelton with nitro and amino substitution group and it was
      revealed to be 4-amino-3,3'-dichloro-5,4'-dinitrobiphenyl derived from chemical
      plants treating polymers and dye intermediates. However, the identification of
      major putative mutagenic/genotoxic compounds in most surface waters with high
      mutagenic/genotoxic activity in the world have not been performed. Further
      efforts on chemical isolation and identification by bioassay-directed chemical
      analysis should be performed.

PMID- 15572285
TI  - The mutagenic hazards of aquatic sediments: a review.
AB  - Sediments are the sink for particle-sorbed contaminants in aquatic systems and
      can serve as a reservoir of toxic contaminants that continually threaten the
      health and viability of aquatic biota. This work is a comprehensive review of
      published studies that investigated the genotoxicity of sediments in rivers,
      lakes and marine habitats. The Salmonella mutagenicity test is the most
      frequently used assay and accounts for 41.1% of the available data. The
      Salmonella data revealed mutagenic potency values for sediment extracts (in
      revertants per gram dry weight) that spans over seven orders of magnitude from
      not detectable to highly potent (10(5) rev/g). Analyses of the Salmonella data
      (n=510) showed significant differences between rural, urban/industrial, and
      heavily contaminated (e.g., dump) sites assessed using TA98 and TA100 with S9
      activation. Additional analyses showed a significant positive correlation between
      Salmonella mutagenic potency (TA98 and TA100 with S9) and PAH contamination
      (r2=0.19-0.68). The second and third most commonly used assays for the analysis
      of sediments and sediment extracts are the SOS Chromotest (9.2%) and the Mutatox
      assays (7.8%), respectively. These assays are frequently used for rapid initial
      screening of collected samples. A variety of other in vitro endpoints employing
      cultured fish and mammalian cells have been used to investigate sediment
      genotoxic activity. Endpoints investigated include sister chromatid exchange
      frequency, micronucleus frequency, chromosome aberration frequency, gene mutation
      at tk and hprt loci, unscheduled DNA synthesis, DNA adduct frequency, and DNA
      strand break frequency. More complex in vivo assays have documented a wide range
      of effects including neoplasms and preneoplastic lesions in fish and invertebrate
      exposed ex situ. Although costly and time consuming, these assays have provided
      definitive evidence linking sediment contamination and a variety of genotoxic and
      carcinogenic effects observed in situ.

PMID- 15572286
TI  - Mutagens in contaminated soil: a review.
AB  - The intentional and accidental discharges of toxic pollutants into the
      lithosphere results in soil contamination. In some cases (e.g., wood preserving
      wastes, coal-tar, airborne combustion by-products), the contaminated soil
      constitutes a genotoxic hazard. This work is a comprehensive review of published
      information on soil mutagenicity. In total, 1312 assessments of genotoxic
      activity from 118 works were examined. The majority of the assessments (37.6%)
      employed the Salmonella mutagenicity test with strains TA98 and/or TA100. An
      additional 37.6% of the assessments employed a variety of plant species (e.g.,
      Tradescantia clone 4430, Vicia faba, Zea mays, Allium cepa) to assess mutagenic
      activity. The compiled data on Salmonella mutagenicity indicates significant
      differences (p<0.0001) in mean potency (revertents per gram dry weight) between
      industrial, urban, and rural/agricultural sites. Additional analyses showed
      significant empirical relationships between S9-activated TA98 mutagenicity and
      soil polycyclic aromatic hydrocarbon (PAH) concentration (r2=0.19 to 0.25,
      p<0.0001), and between direct-acting TA98 mutagenicity and soil dinitropyrene
      (DNP) concentration (r2=0.87, p<0.0001). The plant assay data revealed excellent
      response ranges and significant differences between heavily contaminated,
      industrial, rural/agricultural, and reference sites, for the anaphase aberration
      in Allium cepa (direct soil contact) and the waxy locus mutation assay in Zea
      mays (direct soil contact). The Tradescantia assays appeared to be less
      responsive, particularly for exposures to aqueous soil leachates. Additional data
      analyses showed empirical relationships between anaphase aberrations in Allium,
      or mutations in Arabidopsis, and the 137Cs contamination of soils. Induction of
      micronuclei in Tradescantia is significantly related to the soil concentration of
      several metals (e.g., Sb, Cu, Cr, As, Pb, Cd, Ni, Zn). Review of published
      remediation exercises showed effective removal of genotoxic petrochemical wastes
      within one year. Remediation of more refractory genotoxic material (e.g.,
      explosives, creosote) frequently showed increases in mutagenic hazard that
      remained for extended periods. Despite substantial contamination and mutagenic
      hazards, the risk of adverse effect (e.g., mutation, cancer) in humans or
      terrestrial biota is difficult to quantify.

PMID- 15572287
TI  - The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity.
AB  - Mutagens in urban air pollution come from anthropogenic sources (especially
      combustion sources) and are products of airborne chemical reactions. Bacterial
      mutation tests have been used for large, multi-site, and/or time series studies,
      for bioassay-directed fractionation studies, for identifying the presence of
      specific classes of mutagens, and for doing site- or source-comparisons for
      relative levels of airborne mutagens. Early research recognized that although
      carcinogenic PAHs were present in air samples they could not account for the
      majority of the mutagenic activity detected. The mutagenicity of airborne
      particulate organics is due to at least 500 identified compounds from varying
      chemical classes. Bioassay-directed fractionation studies for identifying
      toxicants are difficult to compare because they do not identify all of the
      mutagens present, and both the analytical and bioassay protocols vary from study
      to study. However, these studies show that the majority of mutagenicity is
      usually associated with moderately polar/highly polar classes of compounds that
      tend to contain nitroaromatic compounds, aromatic amines, and aromatic ketones.
      Smog chamber studies have shown that mutagenic aliphatic and aromatic nitrogen
      containing compounds are produced in the atmosphere when organic compounds (even
      non-mutagenic compounds) are exposed to nitrogen oxides and sunlight. Reactions
      that occur in the atmosphere, therefore, can have a profound effect on the
      genotoxic burden of ambient air. This review illustrates that the mutagenesis
      protocol and tester strains should be selected based on the design and purpose of
      the study and that the correlation with animal cancer bioassay results depends
      upon chemical class. Future emphasis needs to be placed on volatile and semi
      volatile genotoxicants, and on multi-national studies that identify, quantify,
      and apportion mutagenicity. Initial efforts at replacing the Salmonella assay for
      ambient air studies with some emerging technology should be initiated.

PMID- 15572288
TI  - The mutagenic hazards of settled house dust: a review.
AB  - Given the large proportion of time people spend indoors, the potential health
      risks posed by chemical contaminants in the indoor environment are of concern.
      Research suggests that settled house dust (SHD) may be a significant source for
      indoor exposure to hazardous substances including polycyclic aromatic
      hydrocarbons (PAHs). Here, we summarize the literature on the mutagenic hazards
      of SHD and the presence of PAHs in dust. We assess the extent to which PAHs are
      estimated to contribute to the mutagenicity of SHD, and evaluate the carcinogenic
      risks associated with exposures to PAHs in SHD. Research demonstrates that SHD
      has a Salmonella TA98 mutagenic potency of 1000-7000 revertants/g, and contains
      between 0.5 and 500 microg/g of PAHs. Although they only account for a small
      proportion of the variability, analyses of pooled datasets suggest that cigarette
      smoking and an urban location contribute to higher levels of PAHs. Despite their
      presence, our calculations show that PAHs likely account for less than 25% of the
      overall mutagenic potency of dust. Nevertheless, carcinogenic PAHs in dust can
      pose potential health risks, particularly for children who play and crawl on
      dusty floors, and exhibit hand-to-mouth behaviour. Risk assessment calculations
      performed in this study reveal that the excess cancer risks from non-dietary
      ingestion of carcinogenic PAHs in SHD by preschool aged children is generally in
      the range of what is considered acceptable (1 x 10(-6) to 2 x 10(-6)).
      Substantially elevated risk estimates in the range 1.5 x 10(-4) to 2.5 x 10(-4)
      correspond only to situations where the PAH content is at or beyond the 95th
      percentile, and the risk estimates are adjusted for enhanced susceptibility at
      early life stages. Analyses of SHD and its contaminants provide an indication of
      indoor pollution and present important information for human exposure
      assessments.

PMID- 15572289
TI  - Genotoxicity of environmental tobacco smoke: a review.
AB  - Environmental tobacco smoke (ETS), or second-hand smoke, is a widespread
      contaminant of indoor air in environments where smoking is not prohibited. It is
      a significant source of exposure to a large number of substances known to be
      hazardous to human health. Numerous expert panels have concluded that there is
      sufficient evidence to classify involuntary smoking (or passive smoking) as
      carcinogenic to humans. According to the recent evaluation by the International
      Agency for Research on Cancer, involuntary smoking causes lung cancer in never
      smokers with an excess risk in the order of 20% for women and 30% for men. The
      present paper reviews studies on genotoxicity and related endpoints carried out
      on ETS since the mid-1980s. The evidence from in vitro studies demonstrates
      induction of DNA strand breaks, formation of DNA adducts, mutagenicity in
      bacterial assays and cytogenetic effects. In vivo experiments in rodents have
      shown that exposure to tobacco smoke, whole-body exposure to mainstream smoke
      (MS), sidestream smoke (SS), or their mixture, causes DNA single strand breaks,
      aromatic adducts and oxidative damage to DNA, chromosome aberrations and
      micronuclei. Genotoxicity of transplacental exposure to ETS has also been
      reported. Review of human biomarker studies conducted among non-smokers with
      involuntary exposure to tobacco smoke indicates presence of DNA adducts, urinary
      metabolites of carcinogens, urinary mutagenicity, SCEs and hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) gene mutations (in newborns exposed through
      involuntary smoking of the mother). Studies on human lung cancer from smokers and
      never-smokers involuntarily exposed to tobacco smoke suggest occurrence of
      similar kinds of genetic alterations in both groups. In conclusion, these
      overwhelming data are compatible with the current knowledge on the mechanisms of
      carcinogenesis of tobacco-related cancers, occurring not only in smokers but with
      a high biological plausibility also in involuntary smokers.

PMID- 15572290
TI  - Genotoxicity of tobacco smoke and tobacco smoke condensate: a review.
AB  - This report reviews the literature on the genotoxicity of mainstream tobacco
      smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic
      in nearly all systems in which it has been tested, with the base/neutral
      fractions being the most mutagenic. In rodents, cigarette smoke induces sister
      chromatid exchanges (SCEs) and micronuclei in bone marrow and lung cells. In
      humans, newborns of smoking mothers have elevated frequencies of HPRT mutants,
      translocations, and DNA strand breaks. Sperm of smokers have elevated frequencies
      of aneuploidy, DNA adducts, strand breaks, and oxidative damage. Smoking also
      produces mutagenic cervical mucus, micronuclei in cervical epithelial cells, and
      genotoxic amniotic fluid. These data suggest that tobacco smoke may be a human
      germ-cell mutagen. Tobacco smoke produces mutagenic urine, and it is a human
      somatic-cell mutagen, producing HPRT mutations, SCEs, microsatellite instability,
      and DNA damage in a variety of tissues. Of the 11 organ sites at which smoking
      causes cancer in humans, smoking-associated genotoxic effects have been found in
      all eight that have been examined thus far: oral/nasal, esophagus,
      pharynx/larynx, lung, pancreas, myeoloid organs, bladder/ureter, uterine cervix.
      Lung tumors of smokers contain a high frequency and unique spectrum of TP53 and
      KRAS mutations, reflective of the PAH (and possibly other) compounds in the
      smoke. Further studies are needed to clarify the modulation of the genotoxicity
      of tobacco smoke by various genetic polymorphisms. These data support a model of
      tobacco smoke carcinogenesis in which the components of tobacco smoke induce
      mutations that accumulate in a field of tissue that, through selection, drive the
      carcinogenic process. Most of the data reviewed here are from studies of human
      smokers. Thus, their relevance to humans cannot be denied, and their explanatory
      powers not easily dismissed. Tobacco smoke is now the most extreme example of a
      systemic human mutagen.

PMID- 15572291
TI  - Dietary flavonoids and cancer risk: evidence from human population studies.
AB  - High dietary intake of fruits and vegetables is consistently associated with a
      reduced risk of common human cancers, including cancers of the lung, breast,
      prostate, and colon. It is unknown which bioactive compound or compounds in plant
      foods provide the chemoprotective effects. One class of compounds currently under
      investigation is flavonoids, a large group of compounds with similar structure,
      consisting of two phenolic benzene rings linked to a heterocyclic pyran or
      pyrone. Although there are numerous in vitro and animal model data suggesting
      that flavonoids influence important cellular and molecular mechanisms related to
      carcinogenesis, such as cell cycle control and apoptosis, there are limited data
      from human population studies. This article reviews data from four cohort studies
      and six case-control studies, which have examined associations of flavonoid
      intake with cancer risk. There is consistent evidence from these studies that
      flavonoids, especially quercetin, may reduce the risk of lung cancer. Further
      research using new dietary databases for food flavonoid content is needed to
      confirm these findings before specific public health recommendations about
      flavonoids can be formulated.

PMID- 15572292
TI  - Insulin-like growth factor-I, soy protein intake, and breast cancer risk.
AB  - Previous studies have found that estrogen enhances the effect of insulin-like
      growth factor-I (IGF-I) levels on breast cancer cell growth. Participants in the
      Shanghai Breast Cancer Study (SBCS) consumed large amounts of soy that was high
      in isoflavones, which act as weak estrogens and as anti-estrogens. We assessed
      whether soy protein intake modified the effect of IGF-I levels on breast cancer
      risk. The SBCS is a population-based case-control study of breast cancer among
      women aged 25-64 conducted between 1996 and 1998 in urban Shanghai. In-person
      interviews were completed with 1,459 incident breast cancer cases ascertained
      through a population-based cancer registry and 1,556 controls randomly selected
      from the general population (with respective response rates of 91% and 90%). This
      analysis is restricted to the 397 cases and 397 matched controls for whom
      information on IGF-I levels was available. For premenopausal breast cancer, we
      found nearly significant interactions between soy protein intake and IGF-I levels
      (P = 0.080) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels (P
      = 0.057). The direction of the interaction appeared to be negative for IGF-I
      levels but was positive for IGFBP-3 levels. No interaction was evident between
      soy protein intake and IGF-I or IGFBP-3 levels among postmenopausal women. Our
      results suggest that soy protein intake may negatively modulate the effect of IGF
      I and may positively modulate the effect of IGFBP-3 levels on premenopausal
      breast cancer risk. Further studies are needed to confirm our finding and to
      understand the biological mechanisms of these potential interactions.

PMID- 15572293
TI  - Eating frequency and colon cancer risk.
AB  - Increased exposure of the colon to bile acids, as a result of increased eating
      frequency, might promote the development of colon cancer. Our aim was to evaluate
      the association between eating frequency and colon cancer. We used data from a
      population-based case-control study of colon cancer in North Carolina. Eating
      frequency (a combination of meals and snacks) was categorized as fewer than
      three, three or four, or more than four eating episodes per day. Multivariate
      logistic regression was used to calculate odds ratios (ORs) for the association
      between eating frequency and colon cancer, adjusting for confounders. We also
      performed stratified analyses to evaluate for differences by sex, coffee intake,
      or tumor site. Six hundred thirty-six participants with colon cancer and 1,048
      control participants were included. The effect of eating frequency on colon
      cancer differed by sex. Among men, participants in the lowest group of eating
      frequency had approximately half the risk of colon cancer compared with the
      middle group (adjusted OR = 0.53; 95% confidence interval, CI = 0.30-0.92).
      Compared with the middle group, men in the highest group had no greater risk of
      cancer (adjusted OR = 1.03; 95% CI = 0.74-1.44). No significant associations were
      detected among women. Decreased eating frequency was associated with a lower risk
      of colon cancer among men but not women.

PMID- 15572294
TI  - Diet and colorectal cancer mortality: results from the Japan Collaborative Cohort
      Study.
AB  - The relationship between diet and colorectal cancer mortality was analyzed in a
      prospective study of 45,181 men and 62,643 women aged 40-79 yr enrolled in the
      Japan Collaborative Cohort Study. Between 1988 and 1990, subjects completed a
      self-administered questionnaire on their sociodemographic characteristics, diet,
      and other lifestyle habits. During the follow-up period (average 9.9 yr), 284
      colon cancer deaths (138 men and 146 women) and 173 rectal cancer deaths (116 men
      and 57 women) were confirmed. The only significant association of colorectal
      cancer mortality with vegetable intake was observed between male rectal cancer
      mortality and green leafy vegetable consumption [hazard ratio (HR) using Cox
      proportional hazard models = 0.6; 95% confidence interval (CI) = 0.3-0.9; P for
      trend = 0.02]. Yogurt intake was also inversely associated with male rectal
      cancer mortality (HR = 0.5; 95% CI = 0.2-1.0; P for trend = 0.04). Egg
      consumption was positively associated with male colon cancer mortality (P for
      trend = 0.04). Women with high fruit consumption had increased colon cancer
      mortality (HR = 1.6; 95% CI = 1.0-2.6; P for trend = 0.04). It should be noted
      that this study lacked statistical power due to small sample size and measurement
      error in the food-frequency questionnaire. Further investigation is therefore
      necessary to confirm the association between diet and colorectal cancer,
      especially by subsites and gender.

PMID- 15572295
TI  - Dietary habits and risk of urothelial cancer death in a large-scale cohort study
      (JACC Study) in Japan.
AB  - In the present study, the associations of dietary habits with the risk of
      urothelial cancer death were evaluated taking into consideration sex, age, and
      smoking habits. The Japan Collaborative Cohort Study was established in 1988-1990
      and consisted of 47,997 men and 66,520 women observed until the end of 1999. A
      self-administered food-frequency questionnaire was used as a baseline survey.
      Hazard ratios for dietary factors were calculated by Cox's proportional hazards
      model. During the observation period, 63 men and 25 women died of urothelial
      cancer. Increasing age, male gender, and history of smoking were all
      significantly associated with increased risk of urothelial cancer death. A high
      intake of milk and fruits other than oranges reduced the risk significantly and
      dose dependently, in particular among subjects with smoking history. However,
      consumption of butter and yogurt had no associations with the risk. Intakes of
      cabbage, lettuce, green leafy vegetables, carrots, squash, tomatoes, and oranges
      were not significantly associated with the risk. It was suggested that urothelial
      cancer death could be potentially preventable by smoking cessation and regular
      intake of milk and fruit.

PMID- 15572296
TI  - Percutaneous endoscopic gastrostomy for long-term feeding of patients with
      oropharyngeal tumors.
AB  - Secondary malnutrition in patients with oropharyngeal tumors can be the cause of
      substantial morbidity. The present, prospective study examined 30 patients
      receiving treatment for an oropharyngeal tumor. Percutaneous endoscopic
      gastrostomy (PEG) was performed 1 wk prior to the start of therapy in 15
      patients, and 15 patients were temporarily fed by nasogastric tube after surgery.
      Anthropometric and laboratory parameters were measured in both patient groups at
      five defined times. Based on these parameters, the nutritional status of the PEG
      patients was found to be substantially better. The present study was able to show
      that the prophylactic placement of a PEG tube greatly improves the nutritional
      status of the patients before and after surgery and minimizes the catabolism of
      the body's fat depots.

PMID- 15572297
TI  - Effects of soy-derived isoflavones and a high-fat diet on spontaneous mammary
      tumor development in Tg.NK (MMTV/c-neu) mice.
AB  - Phytoestrogens such as isoflavonoids and lignans have been postulated as breast
      cancer protective constituents in soy and whole-grain cereals. We investigated
      the ability of isoflavones (IFs) and flaxseed to modulate spontaneous mammary
      tumor development in female heterozygous Tg.NK (MMTV/c-neu) mice. Two different
      exposure protocols were applied, either from 4 wk of age onward (postweaning) or
      during gestation and lactation (perinatal). In the postweaning exposure study,
      mice were fed IFs or flaxseed in a high-fat diet. In addition, flaxseed in a low
      fat diet was tested. Postweaning exposure to IFs and flaxseed tended to
      accelerate the onset of mammary adenocarcinoma development, although tumor burden
      at necropsy was not changed significantly. Perinatal IF exposure resulted in
      enhanced mammary gland differentiation, but palpable mammary tumor onset was not
      affected. However, tumor burden at necropsy in the perinatal exposure study was
      significantly increased in the medium- and high-IF dose groups. Comparison of
      both exposure scenarios revealed a strongly accelerated onset of tumor growth
      after perinatal high-fat diet exposure compared with the low-fat diet. This study
      shows that breast cancer-modulating effects of phytoestrogens are dependent both
      on the background diet and on the timing of exposure in the life cycle.

PMID- 15572298
TI  - Beef tallow increases apoptosis and decreases aberrant crypt foci formation
      relative to soybean oil in rat colon.
AB  - Although epidemiological studies have implicated red meat as increasing colon
      cancer risk, animal studies have generally not been supportive of such an effect.
      This study examined red meat components, such as beef protein and tallow, on
      markers of colon cancer risk. Rats administered dimethylhydrazine were fed either
      casein or beef protein as the protein source and soybean oil or tallow as the fat
      source in a 2 2 factorial design for 9 wk. There were fewer preneoplastic lesions
      [aberrant crypt foci (ACF)] and a greater apoptotic labeling index (P < 0.05) in
      the distal colonic mucosa of rats fed tallow compared with soybean oil. Fecal
      bile acid concentrations were significantly lower in rats fed tallow compared
      with soybean oil. There were no significant differences in mucosal cell
      proliferation. No significant effects were found due to protein source or to
      interactions between fat and protein sources for ACF, cell proliferation labeling
      indexes, or bile acid concentrations. However, there was a significant protein by
      fat source interaction for the apoptotic labeling index. The decreased number of
      ACF, decreased fecal bile acid concentration, and increased mucosal apoptosis
      with tallow consumption are not consistent with a role for this fat in increasing
      risk of colon cancer.

PMID- 15572299
TI  - The effect of dietary restriction on PhIP-induced mutation in the distal colon
      and B[a]P- and ENU-induced mutation in the liver of the rat.
AB  - A reduction in dietary intake has been shown to significantly increase the
      lifespan of rodents, lower the incidence of tumors, and reduce DNA damage. The
      objective of this study was to determine whether dietary restriction (DR) reduced
      the frequency of mutation induced by two environmentally relevant metabolically
      activated mutagens and one direct-acting mutagen in the lacI transgene of male
      and female Big BlueR rats. Both male and female rats were maintained on either an
      ad libitum (AL) or a 40%-reduced diet for 22 wk. The mutagenicity of a 100-mg/kg
      intraperitoneal injection with 2-amino-1-methyl-6-pheny-imidazo[4,5-b] pyridine
      (PhIP), benzo[a]pyrene (B[a]P), and N-ethyl-N- nitrosourea (ENU) was determined
      in the colon or liver. The results indicated that DR did not significantly alter
      the PhIP-induced mutant frequency in male or female colons. DR completely
      prevented mutagenicity induced by B[a]P in the female liver (2.6 +/- 0.6 10(-5)
      vs 10.9 +/- 5.8 10(-5) in AL females), yet increased the induced frequency in
      male livers (16.3 +/- 3.7 10(-5) vs 10.6 +/- 1.5 10(-5) in AL male livers).
      Although there was no difference in mutation frequency in the liver between AL
      and DR females treated with ENU, there was approximately a 40% decrease in
      induced frequency in DR males compared with AL males. These results indicate that
      a reduction in dietary intake has no preventive effect against PhIP-induced
      mutation in the colon, but has sex-dependent protective effects against B[a]P-
      and ENU-induced mutation in the liver.

PMID- 15572300
TI  - Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and
      apoptosis and inhibits growth of colo 201 human colon cancer cells.
AB  - The effect of conjugated docosahexaenoic acid (CDHA) on the inhibition of colon
      cancer cell growth was examined in the colo 201 human colon cancer cell line, and
      the effect was compared with docosahexaenoic acid (DHA) and eicosapentaenoic acid
      (EPA). CDHA was a more potent tumor cell growth inhibitor than DHA and EPA by
      colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) assay (IC50 for 72 h: 31.6 microM, 46.8 microM,
      and 56.6 microM, respectively). CDHA inhibited cell cycle progression, due to
      accumulation of cells in G1 phase, which involved increased p21Cip1/Waf1 and
      decreased cyclin D1, cyclin E, and proliferating cell nuclear antigen expression;
      the p53 and cyclin A levels were unchanged. Induction of apoptosis was confirmed
      by the appearance of sub-G1 populations, and apoptosis cascade involved
      upregulation of the apoptosis-enhancing proteins (Bak and Bcl-xS) and
      downregulation of the apoptosis-suppressing proteins (Bcl-xL and Bcl-2). CDHA
      modulated cell cycle regulatory proteins and apoptosis-related proteins, similar
      to the effects of DHA. CDHA at a dietary dose of 1.0% significantly inhibited
      growth of colo 201 cells transplanted in nude mice.

PMID- 15572301
TI  - Blackberry extracts inhibit activating protein 1 activation and cell
      transformation by perturbing the mitogenic signaling pathway.
AB  - Blackberries are natural rich sources of bioflavonoids and phenolic compounds
      that are commonly known as potential chemopreventive agents. Here, we
      investigated the effects of fresh blackberry extracts on proliferation of cancer
      cells and neoplastic transformation induced by 12-O-tetradecanoylphorbol-13
      acetate (TPA), as well as the underlying mechanisms of signal transduction
      pathways. Using electron spin resonance, we found that blackberry extract is an
      effective scavenger of free radicals, including hydroxyl and superoxide radicals.
      Blackberry extract inhibited the proliferation of a human lung cancer cell line,
      A549. Pretreatment of A549 cells with blackberry extract resulted in an
      inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation induced by
      ultraviolet B (UVB) irradiation. Blackberry extract decreased TPA-induced
      neoplastic transformation of JB6 P+ cells. Pretreatment of JB6 cells with
      blackberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1
      transactivation. Furthermore, blackberry extract also blocked UVB- or TPA-induced
      phosphorylation of ERKs and JNKs, but not p38 kinase. Overall, these results
      indicated that an extract from fresh blackberry may inhibit tumor promoter
      induced carcinogenesis and associated cell signaling, and suggest that the
      chemopreventive effects of fresh blackberry may be through its antioxidant
      properties by blocking reactive oxygen species-mediated AP-1 and mitogen
      activated protein kinase activation.

PMID- 15572302
TI  - Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and
      caspase-calpain-dependent pathways.
AB  - Flavonoids are polyphenolic phytochemicals that are ubiquitous in plants and
      present in the common human diet. They may exert diverse beneficial effects,
      including antioxidant and anticarcinogenic activities. In this study we tested
      the apoptotic activity of 22 flavonoids and related compounds in leukemic U937
      cells. Several flavones but none of the isoflavones or flavanones tested induced
      apoptotic cell death under these conditions, as determined by reduction in cell
      viability, flow cytometry, and oligonucleosomal DNA fragmentation. Structure
      activity relationship showed that at least two hydroxylations in positions 3, 5,
      and 7 of the A ring were needed to induce apoptosis, whereas hydroxylation in 3'
      and/or 4' of the B ring enhanced proapoptotic activity. At lower concentrations,
      these compounds were also able to sensitize these cells to apoptosis induced by
      tumor necrosis factor-alpha. Regarding the mechanisms, galangin, luteolin,
      chrysin, and quercetin induced apoptosis in a way that required the activation of
      caspases 3 and 8, but not caspase 9. In contrast, an active role of calpains in
      addition to caspases was demonstrated in apoptosis induced by fisetin, apigenin,
      and 3,7-dihydroxyflavone. Our data show evidence of the proapoptotic properties
      of some flavonoids that could support their rational use as chemopreventive and
      therapeutic agents against carcinogenic disease.

PMID- 15572303
TI  - Squalene does not exhibit a chemopreventive activity and increases plasma
      cholesterol in a Wistar rat hepatocarcinogenesis model.
AB  - The eventual chemopreventive effect of squalene (SQ), a triterpene present in
      olive oil, was evaluated when administered to Wistar rats during a period
      comprising the initiation and selection/promotion of the "resistant hepatocyte"
      (RH) model of hepatocarcinogenesis. During 8 consecutive wk, animals received by
      gavage SQ (100 or 150 mg/100 g body weight) dissolved in corn oil (CO) daily.
      Animals treated with only CO and submitted to the RH model were used as controls.
      Treatments with SQ did not result in inhibition of macroscopically visible
      hepatocyte nodules (P > 0.05) or of hepatic placental glutathione S-transferase-
      positive preneoplastic lesions (PNL; P > 0.05). Hepatic cell proliferation and
      apoptosis indexes were not different (P > 0.05) among the different experimental
      groups, both regarding PNL and surrounding normal tissue areas. There were no
      significant differences (P > 0.05) among comets presented by rats treated with
      the two SQ doses or with CO. On the other hand, SQ increased total plasma
      cholesterol levels when administered at both doses (P < 0.05). This indicates
      that the isoprenoid was absorbed. Thus, SQ did not present chemopreventive
      activity during hepatocarcinogenesis and had a hypercholesterolemic effect,
      suggesting caution when considering its use in chemoprevention of cancer.

PMID- 15572305
TI  - Jack C. Hughston, MD: orthopaedist and pioneer of sports medicine.

PMID- 15572307
TI  - Presidential address of the American Orthopaedic Society for Sports Medicine: it
      hurts when I do this.

PMID- 15572308
TI  - Knee stability and graft function after anterior cruciate ligament
      reconstruction: a comparison of a lateral and an anatomical femoral tunnel
      placement.
AB  - BACKGROUND: Locations of femoral tunnels for anterior cruciate ligament
      replacement grafts remain a subject of debate. HYPOTHESIS: A lateral femoral
      tunnel placed at the insertion of the posterolateral bundle of the anterior
      cruciate ligament can restore knee function comparably to anatomical femoral
      tunnel placement. STUDY DESIGN: Controlled laboratory study. METHODS: Ten
      cadaveric knees were subjected to the following external loading conditions: (1)
      a 134-N anterior tibial load and (2) combined rotatory loads of 10-N.m valgus and
      5-N.m internal tibial torques. Data on resulting knee kinematics and in situ
      force of the intact anterior cruciate ligament and anterior cruciate ligament
      graft were collected using a robotic/universal force-moment sensor testing system
      for (1) intact, (2) anterior cruciate ligament-deficient, (3) anatomical double
      bundle reconstructed, and (4) laterally placed single-bundle reconstructed knees.
      RESULTS: In response to anterior tibial load, anterior tibial translation and in
      situ force in the graft were not significantly different between the 2
      reconstructions except at high knee flexion. For example, at 90 degrees of knee
      flexion, anterior tibial translation was 6.1 +/- 2.3 mm for anatomical double
      bundle reconstruction and 7.6 +/- 2.6 mm for laterally placed single-bundle
      reconstruction (P < .05). In response to rotatory loads, there were no
      significant differences between the 2 reconstruction procedures (4.8 +/- 2.4 mm
      vs 4.8 +/- 3.0 mm in anterior tibial translation at 15 degrees of knee flexion, P
      > .05). CONCLUSION: Lateral tunnel placement can restore rotatory and anterior
      knee stability similarly to an anatomical reconstruction when the knee is near
      extension. However, the same is not true when the knee is at high flexion angles.
      CLINICAL RELEVANCE: To reproduce the complex function of the anterior cruciate
      ligament, reproducing both bundles of the anterior cruciate ligament may be
      necessary.

PMID- 15572309
TI  - Revision arthroscopically assisted anterior cruciate ligament reconstruction with
      previously unharvested ipsilateral autografts.
AB  - BACKGROUND: Revision anterior cruciate ligament reconstruction requires
      flexibility and variability in treatment options. This study analyzed the
      functional outcomes and graft stability of 48 consecutive revision anterior
      cruciate ligament reconstructions using previously unharvested ipsilateral
      autografts. HYPOTHESIS: Using previously unharvested ipsilateral autografts will
      achieve similar outcomes to other graft choices in revising previously failed
      anterior cruciate ligament reconstructions. STUDY DESIGN: Prospective
      nonrandomized clinical trial. METHODS: Forty-eight patients (48 operations) were
      observed for 2 to 13 years (mean, 90 months). All agreed to have revision
      reconstruction with ipsilateral autografts. The details of the technique varied
      according to the original graft choice and the abnormality encountered.
      Concomitant procedures were necessary in 40 (84%) of 48 knees. Twenty-three
      patients (48%) had revision reconstruction with previously unharvested
      ipsilateral autogenous hamstring tendons. Ten (21%) were 2-stranded grafts, and
      13 (27%) were 4-stranded (quadrupled) autografts. Twenty-five patients (52%) had
      revision reconstruction with previously unharvested ipsilateral patellar tendon
      autografts, 6 (12%) using the 2-incision rear-entry method and 19 (40%) using the
      single-incision technique. RESULTS: Results were evaluated with Lysholm and
      Gillquist scores and International Knee Documentation Committee ratings,
      including KT-2000 arthrometer examinations. Seventy-three percent of the patients
      had International Knee Documentation Committee normal (A) or nearly normal (B)
      knees (42% of the patients had A knees and 42% had B knees). Twelve percent of
      patients had C knees, and 4% had a D rating. Sixty-seven percent of the knees had
      a KT-2000 arthrometer side-to-side difference of 3 mm or less, and an additional
      21% of the knees had a side-to-side difference of 3 to 5 mm; therefore, 94% of
      the grafts were functional or partially functional. Six percent of grafts had
      more than 5 mm of laxity and were considered failures. CONCLUSIONS: Previously
      unharvested ipsilateral autografts proved reliable in improving function and
      stability in revision anterior cruciate ligament reconstruction. However,
      outcomes were less favorable with revision reconstructions than with primary
      reconstructions.

PMID- 15572310
TI  - Effects of small incongruities in a sheep model of osteochondral autografting.
AB  - BACKGROUND: Exact reconstruction of an osteochondral defect by autogenous
      transplantation (mosaicplasty) is difficult given the variation in joint surface
      contour. Clinical and experimental studies do not show the extent to which
      incongruity can be tolerated in autografting. HYPOTHESIS: Grafted articular
      cartilage will hypertrophy to correct the incongruity created by recession of the
      transplanted surface. STUDY DESIGN: Controlled laboratory study. METHODS: To test
      the response of grafts to incongruities, osteochondral autografts were
      transplanted from the trochlea to the femoral condyle in adult male sheep stifle
      joints. In groups of 6 animals, graft surfaces were placed flush, countersunk 1
      mm or countersunk 2 mm, then histologically analyzed 6 weeks after surgery.
      Cartilage thickness, condition of the articular surfaces, and preservation of
      hyaline characteristics were the primary features compared. RESULTS: Bony union,
      vascularization, and new bone formation were present in all grafts. Cartilage-to
      cartilage healing did not occur. In flush specimens, cartilage changed minimally
      in thickness and histologic architecture. The specimens countersunk 1 mm
      demonstrated significant cartilage thickening (54.7% increase, P <.05).
      Chondrocyte hyperplasia, tidemark advancement, and vascular invasion occurred at
      the chondroosseous junction, and the surface remained smooth. Cartilage necrosis
      and fibrous overgrowth were observed in all grafts countersunk 2 mm. CONCLUSIONS:
      Minimally countersunk autografts possess a capacity for remodeling that can
      correct initial incongruities while preserving hyaline characteristics. Grafts
      placed deeper do not restore the contour or composition of the original articular
      surface. CLINICAL RELEVANCE: If preservation of normal hyaline cartilage is the
      objective, thin grafted articular cartilage can remodel, but the tolerance for
      incongruity is limited and probably less than that reported for an intra
      articular fracture.

PMID- 15572311
TI  - Painful jerk test: a predictor of success in nonoperative treatment of
      posteroinferior instability of the shoulder.
AB  - BACKGROUND: The jerk test has been used as a diagnostic test of the
      posteroinferior instability of the shoulder. Pain may or may not be associated
      with posterior clunking during the jerk test. PURPOSE: To evaluate the presence
      or absence of pain with the jerk test as a predictor of the success of
      nonoperative treatment for posteroinferior instability of the shoulder and to
      identify the pathologic lesion responsible for the pain in the jerk test. STUDY
      DESIGN: Retrospective review of prospectively collected data. METHODS: Eighty-one
      patients (89 shoulders) who had posteroinferior instability with a positive
      posterior clunk in their shoulders during the jerk test were nonoperatively
      treated. The patients were divided into 2 groups with respect to the presence of
      pain in the jerk test: the painless jerk group (54 shoulders) and the painful
      jerk group (35 shoulders). Response to the nonoperative treatment was evaluated
      after at least a 6-month rehabilitation program. Patients who did not respond to
      the rehabilitation underwent arthroscopic examination to identify any pathologic
      lesions. RESULTS: The painful jerk group had a higher failure rate with
      nonoperative treatment (P < .001). In the painless jerk group, 50 shoulders (93%)
      responded to the rehabilitation program after a mean of 4 months. Four shoulders
      (7%) were unresponsive to the rehabilitation. In the painful jerk group, 5
      shoulders (16%) were successful with the rehabilitation, whereas the other 30
      shoulders (84%) failed. All 34 shoulders that were unresponsive to the
      rehabilitation had a variable degree of posteroinferior labral lesions.
      CONCLUSIONS: The jerk test is a hallmark for predicting the prognosis of
      nonoperative treatment for posteroinferior instability. Shoulders with
      symptomatic posteroinferior instability and a painful jerk test have
      posteroinferior labral lesions.

PMID- 15572312
TI  - Nonsteroidal anti-inflammatory drugs and acetaminophen in the treatment of an
      acute muscle injury.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs are frequently used to treat
      muscle injuries in athletes. It is not known whether the anti-inflammatory
      effects of these drugs are important or whether their effectiveness is a result
      of their central analgesic effect. HYPOTHESIS: The effects of nonsteroidal anti
      inflammatory drugs are no different than the effects of an analgesic
      (acetaminophen) without anti-inflammatory action in an experimental, acute muscle
      contusion model. STUDY DESIGN: Controlled animal study. METHODS: A standardized,
      unilateral, nonpenetrating injury was created to the tibialis anterior muscle of
      96 adult male mice. Four treatment groups were used: group 1, placebo treatment;
      group 2, treatment with rofecoxib, a nonsteroidal anti-inflammatory drug with
      cyclooxygenase-2 selectivity, and treatment after the injury; group 3, rofecoxib
      treatment starting 24 hours before the injury; and group 4, acetaminophen
      treatment after the injury. The muscle and the contralateral normal muscle were
      evaluated at 2, 5, and 7 days after injury by grading of gait, wet weight as a
      measure of edema, and histologic evaluation. RESULTS: Group 1 had significantly
      more gait disturbances at day 2 than all other groups (P < .05). No differences
      were found at days 5 and 7. Wet weights showed an increase at day 2 in group 1 (P
      < .01). Again, no differences were found at days 5 and 7. Histology revealed
      similar inflammatory changes at day 2 in all groups, with regeneration of muscle
      fibers at days 5 and 7. CONCLUSIONS: The results indicate that rofecoxib as a
      nonsteroidal anti-inflammatory drug and acetaminophen as a non-nonsteroidal anti
      inflammatory drug analgesic have similar effects. The lack of differences in wet
      weights and histology suggests that the anti-inflammatory effects of rofecoxib
      are not an important feature of its action. CLINICAL RELEVANCE: The routine use
      of nonsteroidal anti-inflammatory drugs in muscle injuries may need to be
      critically evaluated because low-cost and low-risk analgesics may be just as
      effective.

PMID- 15572313
TI  - Menisci are efficiently transduced by recombinant adeno-associated virus vectors
      in vitro and in vivo.
AB  - BACKGROUND: Meniscal tears remain an unsolved problem in sports medicine. Gene
      transfer is a potential approach to enhancing meniscal repair. Recombinant adeno
      associated virus is a method of gene transfer that has advantages over previously
      used approaches to this problem. HYPOTHESIS: Direct gene transfer to meniscal
      cells can be accomplished using recombinant adeno-associated virus in vitro and
      in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: Recombinant adeno
      associated viruses containing the reporter gene lacZ were tested for their
      ability to achieve gene transfer into lapine and human meniscal cells in vitro
      and into lapine meniscal defects in vivo. Results were assessed by detecting beta
      galactosidase, the enzyme encoded by the lacZ gene. RESULTS: Maximal efficiency
      of gene transfer was 81.6% +/- 6.6% for lapine and 87.2% +/- 14.8% for human
      meniscal cells in vitro. Expression of the transferred gene continued for the 28
      day duration of the study. When the recombinant adeno-associated virus vector was
      injected into meniscal tears in a lapine meniscal tear model, transgene
      expression continued in meniscal cells adjacent to the tear for at least 20 days
      in vivo. CONCLUSIONS: The data suggest that recombinant adeno-associated virus
      vectors can directly and efficiently transfer and stably express foreign genes in
      isolated lapine and human meniscal cells in vitro and in lapine meniscal defects
      in vivo. CLINICAL RELEVANCE: This direct gene transfer approach may form a basis
      for improved treatments of meniscal tears.

PMID- 15572314
TI  - The effects of varied joint motion and loading conditions on posterior cruciate
      ligament fiber length behavior.
AB  - BACKGROUND: The posterior cruciate ligament has been described as being composed
      of 2 bands that reciprocally tighten and loosen with knee flexion, but the fiber
      anatomy and behavior may be more complex. HYPOTHESIS: The mechanical effects of
      defined loading conditions at discrete knee joint angles can vary significantly
      within the substance of the posterior cruciate ligament depending on the fiber
      region tested. STUDY DESIGN: Controlled laboratory study. METHODS: Nine intact,
      fresh-frozen cadaveric knees were instrumented with excursion filaments implanted
      within 4 fiber regions of the posterior cruciate ligament. Patterns of fiber
      behavior were analyzed as a function of the variable linear separation distance
      between tibial and femoral fiber attachment sites during joint motion under a
      simulated quadriceps contraction, tibial internal rotation, and tibial external
      rotation. Analysis of variance, the Newman-Keuls multiple comparisons procedure,
      and paired t tests were used to evaluate statistical significance. RESULTS:
      Compared with the control pattern of fiber behavior during unloaded passive knee
      motion from 0 degrees to 120 degrees , the quadriceps force caused loosening of
      most ligament fibers at knee flexion of less than 75 degrees . Tibial internal
      rotation significantly slackened the anterior and central fiber regions near
      extension and significantly tightened the central and posterior fiber regions
      with progressive flexion. External rotation had an effect similar to internal
      rotation on the anterior and central fiber regions but caused significant
      slackening of the posterior fiber regions from 0 degrees to 45 degrees .
      CONCLUSIONS: Distinct geographic regions within the posterior cruciate ligament
      have different functional roles depending on the joint angle and the type of load
      to which the knee is subjected. CLINICAL RELEVANCE: The specific graft placement
      parameters in a given surgical procedure relate to end-to-end length changes of
      the graft and may have important implications for postoperative rehabilitation
      and return to specific functional activities.

PMID- 15572315
TI  - Biomechanical and kinematic influences of a total infrapatellar fat pad resection
      on the knee.
AB  - BACKGROUND: This biomechanical study was performed to evaluate the consequences
      of total infrapatellar fat pad resection on knee kinematics and patellar contact
      pressure. HYPOTHESIS: Resection of the infrapatellar fat pad produces significant
      changes in knee kinematics and patellar contact pressure. STUDY DESIGN:
      Biomechanical cadaveric study. METHODS: Isokinetic knee extension was simulated
      on 10 human knee cadaveric specimens (6 men, 4 women; mean age at death, 44
      years). Joint kinematics were evaluated by an ultrasound-based 3D motion analysis
      system, and retro-patellar contact pressure was measured using an electronic
      pressure-sensitive film. All data were taken before and after resection of the
      infrapatellar fat pad and statistically analyzed. RESULTS: A total resection of
      the infrapatellar fat pad resulted in a significant decrease of the tibial
      external rotation relative to the femur between 63 degrees of flexion and full
      knee extension (maximum: 3 degrees rotation difference at 0 degrees knee flexion,
      P = .011), combined with a significant medial translation of the patella between
      29 degrees and 69 degrees of knee flexion (range, 0.9-1.3 mm, P = .017-.028).
      Retro-patellar contact pressure was significantly reduced (from 20% to 25%, P =
      .008-.021) at all flexion angles. CONCLUSION: A resection of the infrapatellar
      fat influences patellar biomechanics and knee kinematics. CLINICAL RELEVANCE: The
      infrapatellar fat pad may have a biomechanical function and may play a role in
      anterior knee pain syndrome.

PMID- 15572316
TI  - A prospectively randomized double-blind study on the effect of initial graft
      tension on knee stability after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: No consensus exists on the amount of tension that should be applied
      to anterior cruciate ligament grafts to best facilitate graft incorporation and
      re-create normal knee mechanics. HYPOTHESIS: Differences in initial graft tension
      will affect postoperative knee stability. STUDY DESIGN: Prospective, randomized,
      double-blind clinical trial. METHODS: Forty-nine patients undergoing bone
      patellar tendon-bone autograft anterior cruciate ligament reconstruction by a
      single surgeon were randomized into high-tension (n = 27) and low-tension (n =
      22) groups. Grafts were set at 90 N or 45 N. Arthrometric measurements (KT-1000
      arthrometer manual maximum) of anterior tibial displacement and knee range of
      motion were made before surgery and at 1 week and an average of 20 months after
      surgery. Knee outcome scores were collected before and after surgery, and a
      single-leg hop test was also performed at final follow-up. RESULTS: After
      anterior cruciate ligament reconstruction, anterior tibial displacement was
      significantly greater in the patients in the low-tension group (P < .05). The
      side-to-side difference in anterior tibial displacement in the high-tension and
      low-tension groups was 1.1 +/- 1.7 mm versus 2.4 +/- 2.4 mm 1 week after surgery
      and 2.2 +/- 1.6 mm versus 3.0 +/- 2.2 mm at follow-up. Five patients had abnormal
      anterior tibial displacement (>5 mm side-to-side difference), and all were in the
      low-tension group (P <.05). Knee outcome scores improved with surgery (P <.01),
      with similar results for low-tension and high-tension groups. Hop test deficits
      were not different between groups. CONCLUSIONS: Initial graft tension affects the
      restoration of knee stability. A graft tension of 45 N was not sufficient for
      restoring knee stability.

PMID- 15572317
TI  - Functional bracing after anterior cruciate ligament reconstruction: a
      prospective, randomized, multicenter study.
AB  - BACKGROUND: Bracing after anterior cruciate ligament reconstruction is expensive
      and is not proven to prevent injuries or influence outcomes. PURPOSE: To
      determine whether postoperative functional knee bracing influences outcomes.
      STUDY DESIGN: Prospective, randomized, multicenter clinical trial. METHODS: One
      hundred volunteers from the 3 US service academies with acute anterior cruciate
      ligament tears were randomized into braced or nonbraced groups. Only those
      subjects with anterior cruciate ligament tears treated surgically within the
      first 8 weeks of injury were included. Patients with chondral injuries,
      significant meniscal tears, or multiple knee ligament injuries were excluded.
      Surgical procedures and the postoperative physical therapy protocols were
      identical for both groups. The braced group was instructed to wear an off-the
      shelf functional knee brace for all cutting, pivoting, or jumping activities for
      the first year after surgery. RESULTS: Ninety-five subjects were available with a
      minimum 2-year follow-up. There were no statistically significant differences
      between groups in knee stability, functional testing with the single-legged hop
      test, International Knee Documentation Committee scores, Lysholm scores, knee
      range of motion, or isokinetic strength testing. Two braced subjects had
      reinjuries, and 3 nonbraced subjects had reinjuries. CONCLUSIONS: In this young,
      active population, postoperative bracing does not appear to change the clinical
      outcomes after anterior cruciate ligament reconstruction.

PMID- 15572318
TI  - The influence of muscle fatigue on electromyogram and plantar pressure patterns
      as an explanation for the incidence of metatarsal stress fractures.
AB  - BACKGROUND: Stress fractures are common overuse injuries in runners and appear
      most frequently in the metatarsals. PURPOSE: To investigate fatigue-related
      changes in surface electromyographic activity patterns and plantar pressure
      patterns during treadmill running as potential causative factors for metatarsal
      stress fractures. STUDY DESIGN: Prospective cohort study with repeated
      measurements. METHODS: Thirty experienced runners volunteered to participate in a
      maximally exhaustive run above the anaerobic threshold. Surface electromyographic
      activity was monitored for 14 muscles, and plantar pressures were measured using
      an in-shoe monitoring system. Fatigue was documented with blood lactate
      measurements. RESULTS: The results demonstrated an increased maximal force (5%, P
      < .01), peak pressure (12%, P < .001), and impulse (9%, P < .01) under the second
      and third metatarsal head and under the medial midfoot (force = 7%, P < .05;
      pressure = 6%, P < .05; impulse = 17%, P < .01) toward the end of the fatiguing
      run. Contact area and contact time were only slightly affected. The mean
      electromyographic activity was significantly reduced in the medial gastrocnemius
      (-9%, P < .01), lateral gastrocnemius (-12%, P < .01), and soleus (-9%, P < .001)
      muscles. CONCLUSION: The demonstrated alteration of the rollover process with an
      increased forefoot loading may help to explain the incidence of stress fractures
      of the metatarsals under fatiguing loading conditions.

PMID- 15572319
TI  - Arthroscopic Bankart repair using suture anchors in athletes: patient selection
      and postoperative sports activity.
AB  - PURPOSE: The purpose of this study was to evaluate the results in selected high
      risk patients who underwent arthroscopic stabilization of shoulders with
      recurrent anterior instability. HYPOTHESIS: Arthroscopic stabilization using
      suture anchors is useful for athletes younger than 25 years or for contact
      athletes without a large bone loss of glenohumeral articulation. STUDY DESIGN:
      Prospective cohort study. METHODS: The study group comprised 55 patients, with a
      mean follow-up of 42 months (range, 25-72 months). Thirty-two patients had
      recurrent dislocations, 14 had recurrent subluxations, and 9 had recurrent
      subluxations after a single dislocation. Rowe score, range of motion, recurrence,
      and sports activities were evaluated. RESULTS: Mean Rowe score improved from 30.1
      to 92.3 points; 45 scores (82%) were excellent, 5 (9%) good, 1 fair (2%), and 4
      (7%) poor. Patients had lost a mean of 4 degrees of external rotation in
      adduction. Four (7%) had recurrence. The recurrence rate in contact athletes
      (9.5%, 2 of 21) was not statistically different from that in noncontact athletes
      (6%, 2 of 34). Forty-four (80%) returned at the same levels. The complete return
      rate in overhead-throwing athletes (68%, 17 of 25) was lower than that in
      nonoverhead athletes (90%, 27 of 30) (P = .0423). Five patients had
      unsatisfactory results. CONCLUSION: Arthroscopic stabilization is a reliable
      procedure in selected high-risk patients.

PMID- 15572320
TI  - The effect of anterior cruciate ligament reconstruction on the risk of knee
      reinjury.
AB  - BACKGROUND: Although there is evidence that very active, young patients are
      better served with anterior cruciate ligament reconstruction, there is a lack of
      objective data demonstrating that future knee injury is prevented by these
      procedures. HYPOTHESIS: Anterior cruciate ligament reconstruction protects
      against reinjury of the knee that would require reoperation. STUDY DESIGN:
      Retrospective cohort study. METHODS: A cohort of 6576 active-duty army personnel
      who had been hospitalized for anterior cruciate ligament injury from 1990 to 1996
      were identified. Using the Total Army Injury and Health Outcomes Database, the
      authors followed these individuals for up to 9 years and collected clinical,
      demographic, and occupational data. These data were evaluated with bivariate and
      multivariable analyses to determine the effect of anterior cruciate ligament
      reconstruction on the rate of knee reinjury that required operation. RESULTS: Of
      the 6576 study subjects, 3795 subjects (58%) underwent anterior cruciate ligament
      reconstruction and 2781 (42%) did not. The rate of reoperation was significantly
      lower among the anterior cruciate ligament reconstruction group (4.90/100 person
      years) compared with those treated conservatively (13.86/100 person-years; P <
      .0001). Proportional hazard regression analyses adjusted for age, race, sex,
      marital status, education, and physical activity level confirmed that anterior
      cruciate ligament reconstruction was protective against meniscal and cartilage
      reinjury (P < .0001). Secondary medial meniscal injury was more common than
      secondary lateral meniscal injury (P < .003). Younger age was the strongest
      predictor of failure of conservative management leading to late anterior cruciate
      ligament reconstruction (P < .0001). CONCLUSIONS: Anterior cruciate ligament
      reconstruction protected against reoperation in this young, active population;
      younger subjects were more likely to require late anterior cruciate ligament
      reconstruction. CLINICAL RELEVANCE: Strong consideration should be given to
      anterior cruciate ligament reconstruction after anterior cruciate ligament injury
      in young, active individuals.

PMID- 15572321
TI  - The effect of posterior cruciate ligament deficiency on knee kinematics.
AB  - BACKGROUND: Alteration of the kinematics of the PCL-deficient knee might be a
      factor in producing the articular damage. Very little is known about the in vivo
      weightbearing kinematics of the PCL-deficient knee. HYPOTHESIS: Isolated rupture
      of the posterior cruciate ligament alters knee kinematics, predisposing the
      patient to development of early osteoarthritis. STUDY DESIGN: Case series.
      METHODS: Tibiofemoral motion was assessed using open-access magnetic resonance
      imaging, weightbearing in a squat, through the arc of flexion from 0 degrees to
      90 degrees in 6 patients with isolated rupture of the posterior cruciate ligament
      in one knee and a normal contralateral knee. Passive sagittal laxity was assessed
      by performing the posterior and anterior drawer tests while the knees were
      scanned, again using the same magnetic resonance imaging scanner. The
      tibiofemoral positions during this stress magnetic resonance imaging examination
      were measured from midmedial and midlateral sagittal images of the knees.
      RESULTS: Rupture of the posterior cruciate ligament leads to an increase in
      passive sagittal laxity in the medial compartment of the knee (P < .006). In the
      weightbearing scans, posterior cruciate ligament rupture alters the kinematics of
      the knee with persistent posterior subluxation of the medial tibia so that the
      femoral condyle rides up the anterior upslope of the medial tibial plateau. This
      fixed subluxation was observed throughout the extension-flexion arc and was
      statistically significant at all flexion angles (P < .018 at 0 degrees , P < .013
      at 20 degrees , P < .014 at 45 degrees , P < .004 at 90 degrees ). The kinematics
      of the lateral compartment were not altered by posterior cruciate ligament
      rupture. The posterior drawer test showed increased laxity in the medial
      compartment. CONCLUSION: Posterior cruciate ligament rupture alters the
      kinematics of the medial compartment of the knee, resulting in "fixed" anterior
      subluxation of the medial femoral condyle (posterior subluxation of the medial
      tibial plateau). This study helps to explain the observation of increased
      incidence of osteoarthritis in the medial compartment, and specifically the
      femoral condyle, in posterior cruciate ligament-deficient knees.

PMID- 15572322
TI  - In vivo function of the posterior cruciate ligament during weightbearing knee
      flexion.
AB  - BACKGROUND: Current knowledge of posterior cruciate ligament function is mainly
      based on in vitro cadaveric studies. There are few studies on the in vivo
      function of the posterior cruciate ligament. The objective of the study was to
      quantify the multidimensional deformation of the posterior cruciate ligament.
      HYPOTHESIS: During in vivo weightbearing flexion, the posterior cruciate ligament
      undergoes complex 3-dimensional deformations, including elongation, twist, and
      changes in orientation. STUDY DESIGN: In vivo biomechanical study. METHODS:
      Magnetic resonance images of 5 human knees were used to create 3-dimensional
      computer models of each subject's knee, including the insertion areas of the
      posterior cruciate ligament. Orthogonal fluoroscopic images of each subject's
      knee were acquired as a quasi-static lunge was performed. The images and computer
      models were used to reproduce the in vivo motion of the knee. The relative motion
      of the femoral and tibial insertions was described in terms of elongation, twist,
      elevation (the angle between the tibial plateau and posterior cruciate ligament,
      measured in the sagittal plane), and deviation (mediolateral orientation,
      measured in plane of tibial plateau). RESULTS: The length of the posterior
      cruciate ligament increased significantly with increasing flexion. It twisted
      almost 80 degrees as the knee flexed from 0 degrees to 90 degrees . The elevation
      angle remained relatively constant at 50 degrees . The deviation angle was
      medially oriented by 20 degrees at full extension, then decreased to
      approximately 10 degrees at 30 degrees through 90 degrees of flexion. CONCLUSION:
      The posterior cruciate ligament undergoes a complex twisting motion as it
      elongates with flexion. CLINICAL RELEVANCE: During reconstruction, the tunnels
      and graft may need to be placed such that the multidimensional deformation of the
      intact posterior cruciate ligament is reproduced.

PMID- 15572323
TI  - Biomechanical rationale for development of anatomical reconstructions of
      coracoclavicular ligaments after complete acromioclavicular joint dislocations.
AB  - BACKGROUND: Surgical treatments of complete acromioclavicular joint dislocations
      replace or reconstruct the coracoclavicular ligaments with a single structure and
      do not account for the anatomical variance of each ligament in the design.
      PURPOSE: To evaluate the cyclic behavior and structural properties of an anatomic
      tendon reconstruction of the coracoclavicular ligament complex after a simulated
      acromioclavicular joint dislocation. STUDY DESIGN: Controlled laboratory study.
      METHODS: Cyclic loading followed by a load-to-failure protocol (simulated
      dislocation) of the normal coracoclavicular ligament complex was performed and
      repeated after an anatomic reconstruction on the same specimen (n = 9). The
      anatomical reconstruction consisted of a semitendinosus tendon that replicated
      the direction and orientation of both the trapezoid and conoid ligaments.
      RESULTS: The coracoclavicular ligament and anatomical reconstruction complexes
      had clinically insignificant (<3 mm) permanent elongation after cyclic loading.
      The stiffness and ultimate load of the coracoclavicular ligament complex (60.8 +/
      12.2 N/mm and 560 +/- 206 N) were significantly greater than for the anatomical
      reconstruction complex (23.4 +/- 5.2 N/mm and 406 +/- 60 N), respectively (P <
      .05). Further analysis of the complexes revealed a 40% decrease in the bending
      stiffness of the clavicle after the simulated dislocation and failure of the
      normal coracoclavicular ligament complex (P < .05), which contributed to the
      diminished properties of the anatomic reconstruction. CONCLUSIONS: The low level
      of permanent elongation after cyclic loading suggests that the anatomic
      reconstruction complex could withstand early rehabilitation; however, the
      decrease in the structural properties and stiffness of the clavicle should be
      considered in optimizing the anatomic reconstruction technique. CLINICAL
      RELEVANCE: Despite the differences compared to the normal coracoclavicular
      ligament complex, the anatomical reconstruction complex more closely approximates
      the stiffness of the coracoclavicular ligament complex than current surgical
      constructs, and the incorporation of biological tissue could improve the overall
      structural properties with healing.

PMID- 15572324
TI  - Multirater agreement of arthroscopic meniscal lesions.
AB  - BACKGROUND: Establishing the validity of classification schemes is a crucial
      preparatory step that should precede multicenter studies. There are no studies
      investigating the reproducibility of arthroscopic classification of meniscal
      pathology among multiple surgeons at different institutions. HYPOTHESIS:
      Arthroscopic classification of meniscal pathology is reliable and reproducible
      and suitable for multicenter studies that involve multiple surgeons. STUDY
      DESIGN: Multirater agreement study. METHODS: Seven surgeons reviewed a video of
      18 meniscal tears and completed a meniscal classification questionnaire.
      Multirater agreement was calculated based on the proportion of agreement, the
      kappa coefficient, and the intraclass correlation coefficient. RESULTS: There was
      a 46% agreement on the central/peripheral location of tears (kappa = 0.30), an
      80% agreement on the depth of tears (kappa = 0.46), a 72% agreement on the
      presence of a degenerative component (kappa = 0.44), a 71% agreement on whether
      lateral tears were central to the popliteal hiatus (kappa = 0.42), a 73%
      agreement on the type of tear (kappa = 0.63), an 87% agreement on the location of
      the tear (kappa = 0.61), and an 84% agreement on the treatment of tears (kappa =
      0.66). There was considerable agreement among surgeons on length, with an
      intraclass correlation coefficient of 0.78, 95% confidence interval of 0.57 to
      0.92, and P < .001. CONCLUSIONS: Arthroscopic grading of meniscal pathology is
      reliable and reproducible. CLINICAL RELEVANCE: Surgeons can reliably classify
      meniscal pathology and agree on treatment, which is important for multicenter
      trials.

PMID- 15572325
TI  - Ankle syndesmosis sprains in national hockey league players.
AB  - BACKGROUND: Although syndesmosis sprains are less common in sports than lateral
      ankle sprains, they represent a significant source of morbidity. Several studies
      have described the increased recovery time for these injuries in a variety of
      sports. No previous study has described this injury in hockey players.
      HYPOTHESIS: Syndesmosis ankle sprains require a longer recovery time and are less
      common than lateral ankle sprains in elite hockey players. STUDY DESIGN:
      Uncontrolled retrospective review. METHODS: The medical records of the St Louis
      Blues (1994-2001) and Dallas Stars (1991-2001) National Hockey League teams were
      reviewed by the head athletic trainers. Ankle sprains were identified and divided
      into 2 groups: syndesmosis and lateral sprains. Player demographics, treatment,
      and time lost to play were recorded for each injury. RESULTS: Fourteen players
      were diagnosed with syndesmosis sprains, and 5 players sustained lateral sprains
      during this time period. Mean time to return to play in games was 45 days (range,
      6-137 days) for syndesmosis sprains versus 1.4 days (range, 0-6 days) for lateral
      sprains. CONCLUSIONS: Syndesmosis sprains represent a significant injury in
      hockey players with an extended time lost and, unlike in other sports, are a more
      common injury than lateral ankle sprains.

PMID- 15572326
TI  - Thermal microdebridement does not affect the time zero biomechanical properties
      of human patellar tendons.
AB  - BACKGROUND: Thermal microdebridement for the treatment of chronic tendinopathy
      has recently been introduced. The effect of thermal microdebridement on the
      biomechanical properties of human tendons, however, remains unknown. HYPOTHESIS:
      Thermal microdebridement does not affect the biomechanical properties of human
      patellar tendons in a cadaveric model at the time of initial treatment. STUDY
      DESIGN: Controlled laboratory study. METHODS: The central 15 mm of 12 matched,
      human (mean age, 71 years; 8 male, 4 female), fresh-frozen patellar tendons was
      divided into 3 equal 5-mm specimens. The treatment group (n = 12) underwent
      thermal microdebridement with a radiofrequency probe. A sham treatment group (n =
      12) underwent insertion of a deactivated probe. The control group (n = 12)
      underwent no treatment. After treatment, each specimen was tested to failure in a
      servo-hydraulic materials testing machine at an elongation rate of 3 mm/s. One
      way repeated measures analysis of variance was used to determine differences
      between groups. RESULTS: No significant difference in ultimate stress at failure,
      elastic modulus, strain energy density, or strain at maximum load was found
      between the groups. The ultimate stress at failure for the treatment, sham, and
      control groups was 61.0, 66.7, and 63.0 MPa, respectively (P = .653), and the
      strain at maximum load was 0.12, 0.11, and 0.09, respectively (P = .279).
      CONCLUSIONS: Thermal microdebridement does not affect the biomechanical
      properties of cadaveric human patellar tendons at the time of initial treatment.
      CLINICAL RELEVANCE: It may be safe to proceed with aggressive rehabilitation
      after thermal microdebridement of the patellar tendon. However, the results in
      this cadaveric model should be interpreted with caution. Additional studies using
      an in vivo model will be required to completely assess the effects of thermal
      microdebridement on the biomechanical properties of human patellar tendons.

PMID- 15572327
TI  - Healing potential of meniscal tears without repair in knees with anterior
      cruciate ligament reconstruction.
AB  - BACKGROUND: Few previous studies have documented the healing potential of
      meniscal tears that are left to heal without repair. PURPOSE: To determine the
      healing rates of meniscal tears left without repair in knees with anterior
      cruciate ligament reconstruction. STUDY DESIGN: Prospective cohort study.
      METHODS: One hundred and ninety-two knees were evaluated at the time of anterior
      cruciate ligament reconstruction and repeat arthroscopy. The healing rates of 41
      medial and 42 lateral torn menisci without repair were evaluated by the same 2
      surgeons in an identical fashion. RESULTS: Of 41 medial torn menisci left without
      repair, 22 (56%) were considered completely healed, 3 (7%) were incompletely
      healed, 11 (24%) were unhealed, and 5 (10%) had expanded unhealed lesions. Of 42
      lateral torn menisci, 31 (74%) were considered completely healed, 2 (5%) were
      incompletely healed, 6 (14%) were unhealed, and 3 (7%) had expanded unhealed
      lesions. The healing rate of a medial meniscal tear was length dependent and not
      related to reconstructed ligament stability. CONCLUSIONS: Stable meniscal tears
      at the time of anterior cruciate ligament reconstruction possibly could be left
      in situ. However, longer medial meniscal tears are thought to require additional
      stabilizing procedures.

PMID- 15572328
TI  - Flexion-distraction injury of the thoracolumbar spine during squat exercise with
      the smith machine.

PMID- 15572329
TI  - Acute fracture through an intramedullary stabilized chronic tibial stress
      fracture in a basketball player: a case report and literature review.

PMID- 15572330
TI  - Accessory lateral meniscus: a case report.

PMID- 15572331
TI  - Anterior cruciate ligament injuries in children with open physes: evolving
      strategies of treatment.
AB  - Injury to the anterior cruciate ligament is one of the most common sports-related
      injuries of the knee. Before the 1980s, the incidence of this injury in
      skeletally immature patients was thought to be rare. However, with the increasing
      participation of children in sports-related activities and an increased awareness
      and diagnostic capability of the medical community, midsubstance tears of the
      anterior cruciate ligament have become more common in patients with open physes.
      Significant controversy exists regarding management of anterior cruciate ligament
      injuries in children with open physes. Traditional management has been
      nonoperative, consisting of physical therapy, bracing, and activity modification.
      Surgical reconstruction has generally been postponed until the patient is
      nearing, or has reached, skeletal maturity. In contrast to this traditional
      treatment algorithm, the recent literature uniformly indicates that nonoperative
      management of anterior cruciate ligament tears in children results in less than
      optimal results. Compliance is certainly an issue, and even though patients may
      refrain from organized sports activities, they are still going to be "kids."
      Recurrent instability, pain, and an inability to return to the preinjury level of
      athletics often result. Even more worrisome are the risks of secondary meniscal
      tears and the possibility of early degenerative joint disease. Recently, there
      has been an increased interest in early, aggressive operative management to
      restore stability to the immature knee. Proponents of nonoperative treatment
      point to the risk of growth arrest associated with violation of the physis.
      Proponents of early operative stabilization advocate that restoration of
      stability provides for opportunity to return to full activity and provides good
      long-term outcomes, all with minimal risk to the physis. This article reviews
      both the basic science and clinical research on this controversial topic.

PMID- 15572332
TI  - Anterior cruciate ligament reconstruction autograft choice: bone-tendon-bone
      versus hamstring: does it really matter? A systematic review.
AB  - Anterior cruciate ligament graft choice is controversial, with no evidence-based
      consensus available to guide decision making. The study design was evidence-based
      medicine systematic review of randomized controlled trials evaluating patellar
      tendon versus hamstring tendon autografts. A literature review identified 9
      randomized controlled trials comparing patellar tendon and hamstring tendon
      autografts. An evidence-based systematic review was performed. Objective and
      subjective outcomes of interest included surgical technique, rehabilitation,
      instrumented laxity, isokinetic strength, patellofemoral pain, return to
      preinjury activity, and Tegner, Lysholm, Cincinnati, and International Knee
      Documentation Committee-1991 scores. Additional surgery, graft failure, and
      complications were reviewed. Slight increased laxity on arthrometer testing was
      seen in the hamstring population in 3 of 7 studies. Pain with kneeling was
      greater for the patellar tendon population in 4 of 4 studies. Only 1 of 9 studies
      showed increased anterior knee pain in the patellar tendon group. Frequency of
      additional surgery seemed to be related to the fixation method and not graft
      type. No study reported a significant difference in graft failure between
      patellar tendon and hamstring tendon autografts. Objective differences (range of
      motion, isokinetic strength, arthrometer testing) were not detected between
      groups in the majority of studies, suggesting that their sensitivity to detect
      clinical outcomes may be limited. Increased kneeling pain in the patellar tendon
      group was seen consistently in the studies evaluated. Subjective differences in
      anterior knee pain or return-to-activity level were not consistently observed in
      these studies. With numbers available, failure rates were not significantly
      different between groups. These findings suggest that graft type may not be the
      primary determinant for successful outcomes after anterior cruciate ligament
      surgery.

PMID- 15572333
TI  - Molecular imaging using magnetic resonance: new tools for the development of
      tumour therapy.
AB  - Molecular imaging - the exploitation of specific molecules as the source of image
      contrast - promises new insights into disease processes in the laboratory and
      since the imaging modalities employed are applicable clinically, can be used to
      translate this knowledge into new diagnostics and treatments in the clinic. This
      brief review focuses on the use of MR-based molecular imaging techniques for
      developing tumour therapy. As examples, methods for detecting drug-induced tumour
      cell apoptosis; the response of tumours and their susceptibilities to an
      antivascular drug; early signs of tumour immune rejection and methods for
      detecting immune cell infiltration of tumours are described.

PMID- 15572334
TI  - Molecular imaging using hyperpolarized 13C.
AB  - MRI provides unsurpassed soft tissue contrast, but the inherent low sensitivity
      of this modality has limited the clinical use to imaging of water protons. With
      hyperpolarization techniques, the signal from a given number of nuclear spins can
      be raised more than 100 000 times. The strong signal enhancement enables imaging
      of nuclei other than protons, e.g. (13)C and (15)N, and their molecular
      distribution in vivo can be visualized in a clinically relevant time window. This
      article reviews different hyperpolarization techniques and some of the many
      application areas. As an example, experiments are presented where hyperpolarized
      (13)C nuclei have been injected into rabbits, followed by rapid (13)C MRI with
      high spatial resolution (scan time <1 s and 1.0 mm in-plane resolution). The high
      degree of polarization thus enabled mapping of the molecular distribution within
      various organs, a few seconds after injection. The hyperpolarized (13)C MRI
      technique allows a selective identification of the molecules that give rise to
      the MR signal, offering direct molecular imaging.

PMID- 15572335
TI  - The role of functional and molecular imaging in cancer drug discovery and
      development.
AB  - Studies of pharmacokinetics (which is what the body does to the drug) and
      pharmacodynamics (which is what the drug does to the body) are essential
      components of the modern process of cancer drug discovery and development.
      Defining the precise relationship between pharmacokinetics and pharmacodynamics
      is critical. It is especially important to establish a well understood
      pharmacological "audit trail" that links together all of the essential parameters
      of drug action, from the molecular target to the clinical effects. The
      pharmacological audit trail allows us to answer two absolutely crucial questions:
      (1) how much gets there; and (2) what does it do? During the pre-clinical drug
      discovery phase, it is essential that pharmacokinetic/pharmacodynamic (PK/PD)
      properties are optimized, so that the best candidate can be selected for clinical
      development. As part of contemporary mechanistic, hypothesis-testing clinical
      trials, construction of the pharmacological PK/PD audit trail facilitates
      rational decision-making. However, PK/PD endpoints frequently require invasive
      sampling of body fluids and tissues. Non-invasive molecular measurements, e.g.
      using MRI or spectroscopy, or positron emission tomography, are therefore very
      attractive. This review highlights the need for PK/PD endpoints in modern drug
      design and development, illustrates the value of PK/PD endpoints, and emphasises
      the importance of non-invasive molecular imaging in drug development. Examples
      cited include the use of PK/PD endpoints in the development of molecular
      therapeutic drugs such as the Hsp90 molecular chaperone inhibitor 17AAG, as well
      as the development of SR-4554 as a non-invasive probe for the detection of tumour
      hypoxia.

PMID- 15572336
TI  - The role of ultrasound in molecular imaging.
AB  - Ultrasound has received less attention than other imaging modalities for
      molecular imaging, but has a number of potential advantages. It is cheap, widely
      available and portable. Using Doppler methods, flow information can be obtained
      easily and non-invasively. It is arguably the most physiological modality, able
      to image structure and function with less sedation than other modalities. This
      means that function is minimally disturbed, and multiple repeat studies or the
      effect of interventions can easily be assessed. High frame rates of over 200
      frames a second are achievable on current commercial systems, allowing for
      convenient cardiac studies in small animals. It can be used to guide
      interventional or invasive studies, such as needle placement. Ultrasound is also
      unique in being both an imaging and therapeutic tool and its value in gene
      therapy has received much recent interest. Ultrasound biomicroscopy has been used
      for in utero imaging and can guide injection of virus and cells. Ultrahigh
      frequency ultrasound can be used to determine cell mechanical properties. The
      development of microbubble contrast agents has opened many new opportunities,
      including new functional imaging methods, the ability to image capillary flow and
      the possibility of molecular targeting using labelled microbubbles.

PMID- 15572337
TI  - Oncological molecular imaging: nuclear medicine techniques.

PMID- 15572338
TI  - Imaging microvascular structure with contrast enhanced MRI.

PMID- 15572339
TI  - Molecular imaging in vivo: an introduction.

PMID- 15572340
TI  - Ion trafficking through T-type Ca2+ channels: a way to look at channel gating
      position.

PMID- 15572341
TI  - Insulin secretion: a high-affinity Ca2+ sensor after all?

PMID- 15572342
TI  - Capturing ion channel gating: a little salt on the tail does the trick.

PMID- 15572343
TI  - Y3+ block demonstrates an intracellular activation gate for the alpha1G T-type
      Ca2+ channel.
AB  - Classical electrophysiology and contemporary crystallography suggest that the
      activation gate of voltage-dependent channels is on the intracellular side, but a
      more extracellular "pore gate" has also been proposed. We have used the voltage
      dependence of block by extracellular Y(3+) as a tool to locate the activation
      gate of the alpha1G (Ca(V)3.1) T-type calcium channel. Y(3+) block exhibited no
      clear voltage dependence from -40 to +40 mV (50% block at 25 nM), but block was
      relieved rapidly by stronger depolarization. Reblock of the open channel,
      reflected in accelerated tail currents, was fast and concentration dependent.
      Closed channels were also blocked by Y(3+) at a concentration-dependent rate,
      only eightfold slower than open-channel block. When extracellular Ca(2+) was
      replaced with Ba(2+), the rate of open block by Y(3+) was unaffected, but closed
      block was threefold faster than in Ca(2+), suggesting the slower closed-block
      rate reflects ion-ion interactions in the pore rather than an extracellularly
      located gate. Since an extracellular blocker can rapidly enter the closed pore,
      the primary activation gate must be on the intracellular side of the selectivity
      filter.

PMID- 15572344
TI  - A highly Ca2+-sensitive pool of granules is regulated by glucose and protein
      kinases in insulin-secreting INS-1 cells.
AB  - We have used membrane capacitance measurements and carbon-fiber amperometry to
      assay exocytosis triggered by photorelease of caged Ca(2+) to directly measure
      the Ca(2+) sensitivity of exocytosis from the INS-1 insulin-secreting cell line.
      We find heterogeneity of the Ca(2+) sensitivity of release in that a small
      proportion of granules makes up a highly Ca(2+)-sensitive pool (HCSP), whereas
      the bulk of granules have a lower sensitivity to Ca(2+). A substantial HCSP
      remains after brief membrane depolarization, suggesting that the majority of
      granules with high sensitivity to Ca(2+) are not located close to Ca(2+)
      channels. The HCSP is enhanced in size by glucose, cAMP, and a phorbol ester,
      whereas the Ca(2+)-sensitive rate constant of exocytosis from the HCSP is
      unaffected by cAMP and phorbol ester. The effects of cAMP and phorbol ester on
      the HCSP are mediated by PKA and PKC, respectively, because they can be blocked
      with specific protein kinase inhibitors. The size of the HCSP can be enhanced by
      glucose even in the presence of high concentrations of phorbol ester or cAMP,
      suggesting that glucose can increase granule pool sizes independently of
      activation of PKA or PKC. The effects of PKA and PKC on the size of the HCSP are
      not additive, suggesting they converge on a common mechanism. Carbon-fiber
      amperometry was used to assay quantal exocytosis of serotonin (5-HT) from insulin
      containing granules following preincubation of INS-1 cells with 5-HT and a
      precursor. The amount or kinetics of release of 5-HT from each granule is not
      significantly different between granules with higher or lower sensitivity to
      Ca(2+), suggesting that granules in these two pools do not differ in morphology
      or fusion kinetics. We conclude that glucose and second messengers can modulate
      insulin release triggered by a high-affinity Ca(2+) sensor that is poised to
      respond to modest, global elevations of [Ca(2+)](i).

PMID- 15572345
TI  - Protein kinase activation increases insulin secretion by sensitizing the
      secretory machinery to Ca2+.
AB  - Glucose and other secretagogues are thought to activate a variety of protein
      kinases. This study was designed to unravel the sites of action of protein kinase
      A (PKA) and protein kinase C (PKC) in modulating insulin secretion. By using high
      time resolution measurements of membrane capacitance and flash photolysis of
      caged Ca(2+), we characterize three kinetically different pools of vesicles in
      rat pancreatic beta-cells, namely, a highly calcium-sensitive pool (HCSP), a
      readily releasable pool (RRP), and a reserve pool. The size of the HCSP is
      approximately 20 fF under resting conditions, but is dramatically increased by
      application of either phorbol esters or forskolin. Phorbol esters and forskolin
      also increase the size of RRP to a lesser extent. The augmenting effect of
      phorbol esters or forskolin is blocked by various PKC or PKA inhibitors,
      indicating the involvement of these kinases. The effects of PKC and PKA on the
      size of the HCSP are not additive, suggesting a convergent mechanism. Using a
      protocol where membrane depolarization is combined with photorelease of Ca(2+),
      we find that the HCSP is a distinct population of vesicles from those colocalized
      with Ca(2+) channels. We propose that PKA and PKC promote insulin secretion by
      increasing the number of vesicles that are highly sensitive to Ca(2+).

PMID- 15572346
TI  - Salt bridges and gating in the COOH-terminal region of HCN2 and CNGA1 channels.
AB  - Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels and cyclic
      nucleotide-gated (CNG) channels are activated by the direct binding of cyclic
      nucleotides. The intracellular COOH-terminal regions exhibit high sequence
      similarity in all HCN and CNG channels. This region contains the cyclic
      nucleotide-binding domain (CNBD) and the C-linker region, which connects the CNBD
      to the pore. Recently, the structure of the HCN2 COOH-terminal region was solved
      and shown to contain intersubunit interactions between C-linker regions. To
      explore the role of these intersubunit interactions in intact channels, we
      studied two salt bridges in the C-linker region: an intersubunit interaction
      between C-linkers of neighboring subunits, and an intrasubunit interaction
      between the C-linker and its CNBD. We show that breaking these salt bridges in
      both HCN2 and CNGA1 channels through mutation causes an increase in the
      favorability of channel opening. The wild-type behavior of both HCN2 and CNGA1
      channels is rescued by switching the position of the positive and negative
      residues, thus restoring the salt bridges. These results suggest that the salt
      bridges seen in the HCN2 COOH-terminal crystal structure are also present in the
      intact HCN2 channel. Furthermore, the similar effects of the mutations on HCN2
      and CNGA1 channels suggest that these salt bridge interactions are also present
      in the intact CNGA1 channel. As disrupting the interactions leads to channels
      with more favorable opening transitions, the salt bridges appear to stabilize a
      closed conformation in both the HCN2 and CNGA1 channels. These results suggest
      that the HCN2 COOH-terminal crystal structure contains the C-linker regions in
      the resting configuration even though the CNBD is ligand bound, and channel
      opening involves a rearrangement of the C-linkers and, thus, disruption of the
      salt bridges. Discovering that one portion of the COOH terminus, the CNBD, can be
      in the activated configuration while the other portion, the C-linker, is not
      activated has lead us to suggest a novel modular gating scheme for HCN and CNG
      channels.

PMID- 15572347
TI  - On the importance of atomic fluctuations, protein flexibility, and solvent in ion
      permeation.
AB  - Proteins, including ion channels, often are described in terms of some average
      structure and pictured as rigid entities immersed in a featureless solvent
      continuum. This simplified view, which provides for a convenient representation
      of the protein's overall structure, incurs the risk of deemphasizing important
      features underlying protein function, such as thermal fluctuations in the atom
      positions and the discreteness of the solvent molecules. These factors become
      particularly important in the case of ion movement through narrow pores, where
      the magnitude of the thermal fluctuations may be comparable to the ion pore atom
      separations, such that the strength of the ion channel interactions may vary
      dramatically as a function of the instantaneous configuration of the ion and the
      surrounding protein and pore water. Descriptions of ion permeation through narrow
      pores, which employ static protein structures and a macroscopic continuum
      dielectric solvent, thus face fundamental difficulties. We illustrate this using
      simple model calculations based on the gramicidin A and KcsA potassium channels,
      which show that thermal atomic fluctuations lead to energy profiles that vary by
      tens of kcal/mol. Consequently, within the framework of a rigid pore model, ion
      channel energetics is extremely sensitive to the choice of experimental structure
      and how the space-dependent dielectric constant is assigned. Given these
      observations, the significance of any description based on a rigid structure
      appears limited. Creating a conducting channel model from one single structure
      requires substantial and arbitrary engineering of the model parameters, making it
      difficult for such approaches to contribute to our understanding of ion
      permeation at a microscopic level.

PMID- 15572348
TI  - Carboxy-terminal determinants of conductance in inward-rectifier K channels.
AB  - Previous studies suggested that the cytoplasmic COOH-terminal portions of inward
      rectifier K channels could contribute significant resistance barriers to ion
      flow. To explore this question further, we exchanged portions of the COOH termini
      of ROMK2 (Kir1.1b) and IRK1 (Kir2.1) and measured the resulting single-channel
      conductances. Replacing the entire COOH terminus of ROMK2 with that of IRK1
      decreased the chord conductance at V(m) = -100 mV from 34 to 21 pS. The slope
      conductance measured between -60 and -140 mV was also reduced from 43 to 31 pS.
      Analysis of chimeric channels suggested that a region between residues 232 and
      275 of ROMK2 contributes to this effect. Within this region, the point mutant
      ROMK2 N240R, in which a single amino acid was exchanged for the corresponding
      residue of IRK1, reduced the slope conductance to 30 pS and the chord conductance
      to 22 pS, mimicking the effects of replacing the entire COOH terminus. This
      mutant had gating and rectification properties indistinguishable from those of
      the wild-type, suggesting that the structure of the protein was not grossly
      altered. The N240R mutation did not affect block of the channel by Ba(2+),
      suggesting that the selectivity filter was not strongly affected by the mutation,
      nor did it change the sensitivity to intracellular pH. To test whether the
      decrease in conductance was independent of the selectivity filter we made the
      same mutation in the background of mutations in the pore region of the channel
      that increased single-channel conductance. The effects were similar to those
      predicted for two independent resistors arranged in series. The mutation
      increased conductance ratio for Tl(+):K(+), accounting for previous observations
      that the COOH terminus contributed to ion selectivity. Mapping the location onto
      the crystal structure of the cytoplasmic parts of GIRK1 indicated that position
      240 lines the inner wall of this pore and affects the net charge on this surface.
      This provides a possible structural basis for the observed changes in
      conductance, and suggests that this element of the channel protein forms a rate
      limiting barrier for K(+) transport.

PMID- 15572349
TI  - KCNE3 truncation mutants reveal a bipartite modulation of KCNQ1 K+ channels.
AB  - The five KCNE genes encode a family of type I transmembrane peptides that
      assemble with KCNQ1 and other voltage-gated K(+) channels, resulting in potassium
      conducting complexes with varied channel-gating properties. It has been recently
      proposed that a triplet of amino acids within the transmembrane domain of KCNE1
      and KCNE3 confers modulation specificity to the peptide, since swapping of these
      three residues essentially converts the recipient KCNE into the donor (Melman,
      Y.F., A. Domenech, S. de la Luna, and T.V. McDonald. 2001. J. Biol. Chem.
      276:6439-6444). However, these results are in stark contrast with earlier KCNE1
      deletion studies, which demonstrated that a COOH-terminal region, highly
      conserved between KCNE1 and KCNE3, was responsible for KCNE1 modulation of KCNQ1
      (Tapper, A.R., and A.L. George. 2000 J. Gen. Physiol. 116:379-389.). To ascertain
      whether KCNE3 peptides behave similarly to KCNE1, we examined a panel of NH(2)-
      and COOH-terminal KCNE3 truncation mutants to directly determine the regions
      required for assembly with and modulation of KCNQ1 channels. Truncations lacking
      the majority of their NH(2) terminus, COOH terminus, or mutants harboring both
      truncations gave rise to KCNQ1 channel complexes with basal activation, a
      hallmark of KCNE3 modulation. These results demonstrate that the KCNE3
      transmembrane domain is sufficient for assembly with and modulation of KCNQ1
      channels and suggests a bipartite model for KCNQ1 modulation by KCNE1 and KCNE3
      subunits. In this model, the KCNE3 transmembrane domain is active in modulation
      and overrides the COOH terminus' contribution, whereas the KCNE1 transmembrane
      domain is passive and reveals COOH-terminal modulation of KCNQ1 channels. We
      furthermore test the validity of this model by using the active KCNE3
      transmembrane domain to functionally rescue a nonconducting, yet assembly and
      trafficking competent, long QT mutation located in the conserved COOH-terminal
      region of KCNE1.

PMID- 15572350
TI  - Biophysical characterization of ERp29. Evidence for a key structural role of
      cysteine 125.
AB  - ERp29 is a major resident of the endoplasmic reticulum (ER) that seemingly plays
      an important role in most animal cells. Although a protein-folding association is
      widely supported, ERp29's specific molecular function remains unknown. A
      chaperone activity was postulated from evidence that ERp29 forms multimers like
      the classical ER chaperones, but conflicting results have emerged from our recent
      studies. Here a biophysical approach was used to clarify this issue and also
      reveal a key structural role for ERp29's characteristic cysteine, Cys-125.
      Applying hydrodynamic parameters derived from sedimentation and dynamic light
      scattering analyses, a model of ERp29's quaternary structure was assembled from
      existing tertiary substructures. Comparison with Windbeutel, an ERp29-like
      protein from fruit fly with specialized chaperone activity, revealed similar tri
      lobar gross structures but some finer differences consistent with functional
      divergence. Solubility and hydrophobic probe assays revealed moderate surface
      hydrophobicity, which was reduced in mutant ERp29 in which serine replaced Cys
      125. This mutant was also relatively labile to proteolytic degradation, providing
      two reasons for the strict conservation of Cys-125. No multimerization was
      observed with untagged ERp29, which existed as tight homodimers (K(d) < 50 nm),
      whereas His-tagged ERp29 artifactually formed 670-kDa oligomers. These findings
      distinguish ERp29 biophysically from its peers in the ER including Windbeutel,
      endorsing our postulate that ERp29 adds a distinct type of folding activity to
      the ER machinery. By invoking novel functional associations for Cys-125 and the
      adjoining linker, new clues about how ERp29 might work have also arisen.

PMID- 15572351
TI  - Interaction of DNA fragmentation factor (DFF) with DNA reveals an unprecedented
      mechanism for nuclease inhibition and suggests that DFF can be activated in a DNA
      bound state.
AB  - DNA fragmentation factor (DFF) is a complex of the DNase DFF40 (CAD) and its
      chaperone/inhibitor DFF45 (ICAD-L) that can be activated during apoptosis to
      induce DNA fragmentation. Here, we demonstrate that DFF directly binds to DNA in
      vitro without promoting DNA cleavage. DNA binding by DFF is mediated by the
      nuclease subunit, which can also form stable DNA complexes after release from
      DFF. Recombinant and reconstituted DFF is catalytically inactive yet proficient
      in DNA binding, demonstrating that the nuclease subunit in DFF is inhibited in
      DNA cleavage but not in DNA binding, revealing an unprecedented mode of nuclease
      inhibition. Activation of DFF in the presence of naked DNA or isolated nuclei
      stimulates DNA degradation by released DFF40 (CAD). In transfected HeLa cells
      transiently expressed DFF associates with chromatin, suggesting that DFF could be
      activated during apoptosis in a DNA-bound state.

PMID- 15572352
TI  - A family of basic amino acid transporters of the vacuolar membrane from
      Saccharomyces cerevisiae.
AB  - Among the members of the major facilitator superfamily of Saccharomyces
      cerevisiae, we identified genes involved in the transport into vacuoles of the
      basic amino acids histidine, lysine, and arginine. ATP-dependent uptake of
      histidine and lysine by isolated vacuolar membrane vesicles was impaired in
      YMR088c, a vacuolar basic amino acid transporter 1 (VBA1)-deleted strain, whereas
      uptake of tyrosine or calcium was little affected. This defect in histidine and
      lysine uptake was complemented fully by introducing the VBA1 gene and partially
      by a gene encoding Vba1p fused with green fluorescent protein, which was
      determined to localize exclusively to the vacuolar membrane. A defect in the
      uptake of histidine, lysine, or arginine was also observed in the vacuolar
      membrane vesicles of mutants YBR293w (VBA2) and YCL069w (VBA3). These three VBA
      genes are closely related phylogenetically and constitute a new family of basic
      amino acid transporters in the yeast vacuole.

PMID- 15572353
TI  - Cell-free transport from the trans-golgi network to late endosome requires
      factors involved in formation and consumption of clathrin-coated vesicles.
AB  - Transport between the trans-Golgi network (TGN) and late endosome represents a
      conserved, clathrin-dependent sorting event that separates lysosomal from
      secretory cargo molecules and is also required for localization of integral
      membrane proteins to the TGN. Previously, we reported a cell-free reaction that
      reconstitutes transport from the yeast TGN to the late endosome/prevacuolar
      compartment (PVC) and requires the PVC t-SNARE Pep12p. Here, we report that
      factors required both for formation of clathrin-coated vesicles at the TGN (the
      Chc1p clathrin heavy chain and the Vps1p dynamin homolog) and for vesicle fusion
      at the PVC (the Vps21p rab protein and Vps45p SM (Sec1/Munc18) protein) are
      required for cell-free transport. The marker for TGN-PVC transport, Kex2p, is
      initially present in a clathrin-containing membrane compartment that is competent
      for delivery of Kex2p to the PVC. A Kex2p chimera containing the cytosolic tail
      (C-tail) of the vacuolar protein sorting receptor, Vps10p, is also efficiently
      transported to the PVC. Antibodies against the Kex2p and Vps10p C-tails
      selectively block transport of Kex2p and the Kex2-Vps10p chimera. The
      requirements for factors involved in vesicle formation and fusion, the
      identification of the donor compartment as a clathrin-containing membrane, and
      the need for accessibility of C-tail sequences argue that the TGN-PVC transport
      reaction involves selective incorporation of TGN cargo molecules into clathrin
      coated vesicle intermediates. Further biochemical dissection of this reaction
      should help elucidate the molecular requirements and hierarchy of events in TGN
      to-PVC sorting and transport.

PMID- 15572354
TI  - Protein kinase C modulates agonist-sensitive release of Ca2+ from internal stores
      in HEK293 cells overexpressing the calcium sensing receptor.
AB  - This study examined the mechanism of Ca2+ entry and the role of protein kinase C
      (PKC) in Ca2+ signaling induced by activation of the calcium sensing receptor
      (CaR) in HEK293 cells stably expressing the CaR. We demonstrate that influx of
      Ca2+ following CaR activation exhibits store-operated characteristics in being
      associated with Ca2+ store depletion and inhibited by 2-aminoethoxydiphenyl
      borate. Inhibition of PKC with GF109203X, Go6983, or Go6976 and down-regulation
      of PKC activity enhanced the release of Ca2+ from internal stores in response to
      the polyvalent cationic CaR agonist neomycin, whereas activation of PKC with
      acute 12-O-tetradecanoylphorbol-13-acetate treatment decreased the release. In
      contrast, overexpression of wild type PKC-alpha or -epsilon augmented the
      neomycin-induced release of Ca2+ from internal stores, whereas dominant negative
      PKC-epsilon strongly decreased the release, but dominant negative PKC-alpha had
      little effect. Prolonged treatment of cells with 12-O-tetradecanoylphorbol-13
      acetate effectively down-regulated immunoreactive PKC-alpha but had little effect
      on the expression of PKC-epsilon. Together these results indicate that
      diacylglycerol-responsive PKC isoforms differentially influence CaR agonist
      induced release of Ca2+ from internal stores. The fundamentally different results
      obtained when overexpressing or functionally down-regulating specific PKC
      isoforms as compared with pharmacological manipulation of PKC activity indicate
      the need for caution when interpreting data obtained with the latter approach.

PMID- 15572355
TI  - Regulation of plant symbiosis receptor kinase through serine and threonine
      phosphorylation.
AB  - We studied the biochemical properties of a plant receptor-like kinase to gain
      insights into the regulatory mechanism of this largest class of plant kinases.
      SYMRK (symbiosis receptor kinase) is required for early signal transduction
      leading to plant root symbioses with nitrogen-fixing rhizobia and phosphate
      acquiring arbuscular mycorrhizal fungi. Amino acid substitutions in positions
      critical for activity of other related kinases cause a nonsymbiotic plant
      phenotype, suggesting that SYMRK kinase activity is required for symbiosis. SYMRK
      is capable of intermolecular autophosphorylation. Nonphosphorylated SYMRK is less
      active than the phosphorylated version, suggesting the phosphorylation status of
      SYMRK determines its activity. Three Ser/Thr residues were identified as residues
      required for full kinase activation through targeted mutagenesis. Using
      quadrupole time-of-flight mass spectrometry analysis, two of these were confirmed
      to be phosphorylated in vitro. These crucial phosphorylation sites are conserved
      among various plant receptor-like kinases as well as animal Pelle/interleukin-1
      receptor associated kinase. Despite the distinct domain architecture of receptor
      like kinases versus Pelle/interleukin-1 receptor associated kinase, our results
      suggest the existence of conserved activation mechanisms.

PMID- 15572356
TI  - Random mutagenesis of the M3 muscarinic acetylcholine receptor expressed in
      yeast: identification of second-site mutations that restore function to a
      coupling-deficient mutant M3 receptor.
AB  - The M(3) muscarinic receptor is a prototypical member of the class A family of G
      protein-coupled receptors (GPCRs). To gain insight into the structural mechanisms
      governing agonist-mediated M(3) receptor activation, we recently developed a
      genetically modified yeast strain (Saccharomyces cerevisiae) which allows the
      efficient screening of large libraries of mutant M(3) receptors to identify
      mutant receptors with altered/novel functional properties. Class A GPCRs contain
      a highly conserved Asp residue located in transmembrane domain II (TM II;
      corresponding to Asp-113 in the rat M(3) muscarinic receptor) which is of
      fundamental importance for receptor activation. As observed previously with other
      GPCRs analyzed in mammalian expression systems, the D113N point mutation
      abolished agonist-induced receptor/G protein coupling in yeast. We then subjected
      the D113N mutant M(3) receptor to PCR-based random mutagenesis followed by a
      yeast genetic screen to recover point mutations that can restore G protein
      coupling to the D113N mutant receptor. A large scale screening effort led to the
      identification of three such second-site suppressor mutations, R165W, R165M, and
      Y250D. When expressed in the wild-type receptor background, these three point
      mutations did not lead to an increase in basal activity and reduced the
      efficiency of receptor/G protein coupling. Similar results were obtained when the
      various mutant receptors were expressed and analyzed in transfected mammalian
      cells (COS-7 cells). Interestingly, like Asp-113, Arg-165 and Tyr-250, which are
      located at the cytoplasmic ends of TM III and TM V, respectively, are also highly
      conserved among class A GPCRs. Our data suggest a conformational link between the
      highly conserved Asp-113, Arg-165, and Tyr-250 residues which is critical for
      receptor activation.

PMID- 15572357
TI  - The Met-196 -> Arg variation of human tumor necrosis factor receptor 2 (TNFR2)
      affects TNF-alpha-induced apoptosis by impaired NF-kappaB signaling and target
      gene expression.
AB  - Tumor necrosis factor-alpha (TNF-alpha)-induced signaling is pivotally involved
      in the pathogenesis of chronic inflammatory diseases. A polymorphism in the TNF
      receptor 2 (TNFR2) gene resulting in a juxtamembrane inversion from methionine
      (TNFR2(196MET)) to arginine (TNFR2(196ARG)) has been genetically associated with
      an increased risk for systemic lupus erythematosus and familial rheumatoid
      arthritis. Albeit the mutation does not affect the TNF binding kinetics of TNFR2,
      the present study provides evidence that the mutation results in a significantly
      lower capability to induce TNFR2-mediated NF-kappaB activation. Pretriggering of
      TNFR2 with a receptor-specific mutein leads to an enhancement of TNFR1-induced
      apoptosis, which is further increased in cells carrying the TNFR2(196ARG)
      variant. A diminished induction of NF-kappaB-dependent target genes conveying
      either anti-apoptotic or pro-inflammatory functions, such as cIAP1, TRAF1, IL-6,
      or IL-8 is observed. The mutated form TNFR2(196ARG) shows a reduction of
      inducible TRAF2 recruitment upon TNF-alpha stimulation. The findings suggest a
      common molecular mechanism for the involvement of the TNFR2(196ARG) variant in
      the etiopathogenesis of different chronic inflammatory disorders.

PMID- 15572358
TI  - Histidine 129 in the 75-kDa subunit of mitochondrial complex I from Yarrowia
      lipolytica is not a ligand for [Fe4S4] cluster N5 but is required for catalytic
      activity.
AB  - Respiratory chain complex I contains 8-9 iron-sulfur clusters. In several cases,
      the assignment of these clusters to subunits and binding motifs is still
      ambiguous. To test the proposed ligation of the tetranuclear iron-sulfur cluster
      N5 of respiratory chain complex I, we replaced the conserved histidine 129 in the
      75-kDa subunit from Yarrowia lipolytica with alanine. In the mutant strain,
      reduced amounts of fully assembled but destabilized complex I could be detected.
      Deamino-NADH: ubiquinone oxidoreductase activity was abolished completely by the
      mutation. However, EPR spectroscopic analysis of mutant complex I exhibited an
      unchanged cluster N5 signal, excluding histidine 129 as a cluster N5 ligand.

PMID- 15572359
TI  - Proteomic analysis of in vivo phosphorylated synaptic proteins.
AB  - In the nervous system, protein phosphorylation is an essential feature of
      synaptic function. Although protein phosphorylation is known to be important for
      many synaptic processes and in disease, little is known about global
      phosphorylation of synaptic proteins. Heterogeneity and low abundance make
      protein phosphorylation analysis difficult, particularly for mammalian tissue
      samples. Using a new approach, combining both protein and peptide immobilized
      metal affinity chromatography and mass spectrometry data acquisition strategies,
      we have produced the first large scale map of the mouse synapse phosphoproteome.
      We report over 650 phosphorylation events corresponding to 331 sites (289 have
      been unambiguously assigned), 92% of which are novel. These represent 79
      proteins, half of which are novel phosphoproteins, and include several highly
      phosphorylated proteins such as MAP1B (33 sites) and Bassoon (30 sites). An
      additional 149 candidate phosphoproteins were identified by profiling the
      composition of the protein immobilized metal affinity chromatography enrichment.
      All major synaptic protein classes were observed, including components of
      important pre- and postsynaptic complexes as well as low abundance signaling
      proteins. Bioinformatic and in vitro phosphorylation assays of peptide arrays
      suggest that a small number of kinases phosphorylate many proteins and that each
      substrate is phosphorylated by many kinases. These data substantially increase
      existing knowledge of synapse protein phosphorylation and support a model where
      the synapse phosphoproteome is functionally organized into a highly
      interconnected signaling network.

PMID- 15572360
TI  - Overcoming the inhibitors of myelin with a novel neurotrophin strategy.
AB  - Myelin inhibitors activate a p75(NTR)-dependent signaling cascade in neurons that
      not only inhibits axonal growth but also prevents neurotrophins (NT) from
      stimulating growth. Most intriguingly, in addition to Trk receptors,
      neurotrophins also bind to p75(NTR). We have designed a "mini-neurotrophin"
      called B(AG) to activate TrkB in the absence of p75(NTR) binding. We find that
      B(AG) is as effective as the natural TrkB ligands (brain-derived neurotrophic
      factor (BDNF) and NT-4) at promoting neurite outgrowth from cerebellar neurons.
      Furthermore, the neurite outgrowth responses stimulated by BDNF and B(AG) are
      inhibited by a common set of reagents, including the Trk receptor inhibitor
      K252a, as well as protein kinase A and phosphoinositide 3-kinase inhibitors.
      However, in contrast to BDNF, B(AG) promotes growth in the presence of a myelin
      inhibitor or when antibodies directly activate the p75(NTR) inhibitory pathway.
      On the basis of this observation, we postulated that the binding of BDNF to the
      p75(NTR) might compromise the ability of BDNF to stimulate neurite outgrowth in
      an inhibitory environment. To test this, we used NGF, and an NGF-derived peptide,
      to compete for the BDNF/p75(NTR) interaction; remarkably, in the presence of
      either agent, BDNF acquired the ability to promote neurite outgrowth in the
      presence of a myelin inhibitor. The data suggest that in an inhibitory
      environment, the BDNF/p75(NTR) interaction compromises regeneration. Agents that
      activate Trk receptors in the absence of p75(NTR) binding, or agents that inhibit
      neurotrophin/p75(NTR) binding, might therefore be better therapeutic candidates
      than neurotrophins.

PMID- 15572361
TI  - IFI16 is an essential mediator of growth inhibition, but not differentiation,
      induced by the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid
      carcinoma cells.
AB  - Activation of Ras or Raf in the human medullary thyroid carcinoma (MTC) cell
      line, TT, induces growth arrest and differentiation via two parallel, yet
      independent, pathways. One of these pathways is intracellular and the other is a
      cell-extrinsic, autocrine/paracrine pathway mediated by the leukemia inhibitory
      factor (LIF)/JAK/STAT pathway. Here, we show that IFI16 is a necessary and
      sufficient downstream effector for LIF effects in MTC cells, specifically
      required for the LIF/JAK/STAT pathway-induced growth inhibition in these cells.
      IFI16 was induced by Raf or LIF. Dominant-negative STAT3 could block the
      induction, indicating that Raf can induce IFI16 only via the cell-extrinsic
      pathway. Knock-down of IFI16 using siRNA abrogated LIF-induced changes in
      cellular levels of E2F1, cyclin D1, and p21WAF/CIP1, and cell cycle arrest. In
      addition, adenovirus-mediated overexpression of IFI16 was sufficient to induce
      growth arrest. In contrast to its essential role for LIF-mediated growth arrest,
      IFI16 was not required for differentiation induced by LIF. Knock-down of IFI16
      could not block changes in differentiation markers of the MTC cells, including
      calcitonin, RET, and cell morphology. Our study identifies IFI16 as an essential
      growth-specific effector of the cell-extrinsic growth inhibitory pathway of
      Ras/Raf signaling in MTC cells.

PMID- 15572362
TI  - Molecular basis of the extreme dilution mottled mouse mutation: a combination of
      coding and noncoding genomic alterations.
AB  - Tyrosinase is the rate-limiting enzyme in melanin biosynthesis. It is an N
      glycosylated, copper-containing transmembrane protein, whose post-translational
      processing involves intracytoplasmic movement from the endoplasmic reticulum to
      the Golgi and, eventually, to the melanosome. The expression of the tyrosinase
      (Tyr) gene is controlled by several regulatory regions including a locus control
      region (LCR) located 15 kb upstream from the promoter region. The extreme
      dilution mottled mutant mice (Tyrc-em) arose spontaneously at the MRC Institute
      in Harwell (United Kingdom) from a chinchilla-mottled mutant (Tyrc-m) stock,
      whose molecular basis corresponds to a rearrangement of 5'-upstream regulatory
      sequences including the LCR of the Tyr gene. Tyrc-em mice display a variegated
      pigmentation pattern in coat and eyes, in agreement with the LCR translocation,
      but also show a generalized hypopigmented phenotype, not seen in Tyrc-m mice.
      Genomic analyses of Tyrc-em mice showed a C1220T nucleotide substitution within
      the Tyr encoding region, resulting in a T373I amino acid change, which abolishes
      an N-glycosylation sequon located in the second metal ion binding site of the
      enzyme. Tyrosinase from Tyrc-em displayed a reduced enzymatic activity in vivo
      and in vitro, compared with wild-type enzyme. Deglycosylation studies showed that
      the mutant protein has an abnormal glycosylation pattern and is partially
      retained in the endoplasmic reticulum. We conclude that the phenotype of the
      extreme dilution mottled mouse mutant is caused by a combination of coding and
      noncoding genomic alterations resulting in several abnormalities that include
      suboptimal gene expression, abnormal protein processing, and reduced enzymatic
      activity.

PMID- 15572363
TI  - Correlation of three-dimensional structures with the antibacterial activity of a
      group of peptides designed based on a nontoxic bacterial membrane anchor.
AB  - To understand the functional differences between a nontoxic membrane anchor
      corresponding to the N-terminal sequence of the Escherichia coli enzyme IIA(Glc)
      and a toxic antimicrobial peptide aurein 1.2 of similar sequence, a series of
      peptides was designed to bridge the gap between them. An alteration of a single
      residue of the membrane anchor converted it into an antibacterial peptide.
      Circular dichroism spectra indicate that all peptides are disordered in water but
      helical in micelles. Structures of the peptides were determined in membrane
      mimetic micelles by solution NMR spectroscopy. The quality of the distance-based
      structures was improved by including backbone angle restraints derived from a set
      of chemical shifts ((1)H(alpha), (15)N, (13)C(alpha), and (13)C(beta)) from
      natural abundance two-dimensional heteronuclear correlated spectroscopy.
      Different from the membrane anchor, antibacterial peptides possess a broader and
      longer hydrophobic surface, allowing a deeper penetration into the membrane, as
      supported by intermolecular nuclear Overhauser effect cross-peaks between the
      peptide and short chain dioctanoyl phosphatidylglycerol. An attempt was made to
      correlate the NMR structures of these peptides with their antibacterial activity.
      The activity of this group of peptides does not correlate exactly with helicity,
      amphipathicity, charge, the number of charges, the size of the hydrophobic
      surface, or hydrophobic transfer free energy. However, a correlation is
      established between the peptide activity and membrane perturbation potential,
      which is defined by interfacial hydrophobic patches and basic residues in the
      case of cationic peptides. Indeed, (31)P solid state NMR spectroscopy of lipid
      bilayers showed that the extent of lipid vesicle disruption by these peptides is
      proportional to their membrane perturbation potential.

PMID- 15572364
TI  - Candidate metabolic network states in human mitochondria. Impact of diabetes,
      ischemia, and diet.
AB  - The human mitochondrial metabolic network was recently reconstructed based on
      proteomic and biochemical data. Linear programming and uniform random sampling
      were applied herein to identify candidate steady states of the metabolic network
      that were consistent with the imposed physico-chemical constraints and available
      experimental data. The activity of the mitochondrion was studied under four
      metabolic conditions: normal physiologic, diabetic, ischemic, and dietetic.
      Pairwise correlations between steady-state reaction fluxes were calculated in
      each condition to evaluate the dependence among the reactions in the network.
      Applying constraints on exchange fluxes resulted in predictions for intracellular
      fluxes that agreed with experimental data. Analyses of the steady-state flux
      distributions showed that the experimentally observed reduced activity of
      pyruvate dehydrogenase in vivo could be a result of stoichiometric constraints
      and therefore would not necessarily require enzymatic inhibition. The observed
      changes in the energy metabolism of the mitochondrion under diabetic conditions
      were used to evaluate the impact of previously suggested treatments. The results
      showed that neither normalized glucose uptake nor decreased ketone body uptake
      have a positive effect on the mitochondrial energy metabolism or network
      flexibility. Taken together, this study showed that sampling of the steady-state
      flux space is a powerful method to investigate network properties under different
      conditions and provides a basis for in silico evaluations of effects of potential
      disease treatments.

PMID- 15572365
TI  - Lysophosphatidic acid-operated K+ channels.
AB  - Lysophosphatidic acid (LPA) is an abundant cellular lipid with a myriad of
      biological effects. It plays an important role in both inter- and intracellular
      signaling. Activation of the LPA1-3 G-protein-coupled receptors explains many of
      the extracellular effects of LPA, including cell growth, differentiation,
      survival, and motility. However, LPA also acts intracellularly, activating the
      nuclear hormone receptor peroxisome proliferator-activated receptor-gamma that
      regulates gene transcription. This study shows that the novel subfamily of
      mechano-gated K2P channels comprising TREK-1, TREK-2, and TRAAK is strongly
      activated by intracellular LPA. The LPA-activated 2P domain K+ channels are
      intracellular ligand-gated K+ channels such as the Ca2+- or the ATP-sensitive K+
      channels. LPA reversibly converts these mechano-gated, pH- and voltage-sensitive
      channels into leak conductances. Gating conversion of the 2P domain K+ channels
      by intracellular LPA represents a novel form of ion channel regulation. Thus, the
      TREK and TRAAK channels should be included in the LPA-associated physiological
      and disease states.

PMID- 15572366
TI  - Heparin II domain of fibronectin uses alpha4beta1 integrin to control focal
      adhesion and stress fiber formation, independent of syndecan-4.
AB  - Co-signaling events between integrins and cell surface proteoglycans play a
      critical role in the organization of the cytoskeleton and adhesion forces of
      cells. These processes, which appear to be responsible for maintaining
      intraocular pressure in the human eye, involve a novel cooperative co-signaling
      pathway between alpha5beta1 and alpha4beta1 integrins and are independent of
      heparan sulfate proteoglycans. Human trabecular meshwork cells isolated from the
      eye were plated on type III 7-10 repeats of fibronectin (alpha5beta1 ligand) in
      the absence or presence of the heparin (Hep) II domain of fibronectin. In the
      absence of the Hep II domain, cells had a bipolar morphology with few focal
      adhesions and stress fibers. The addition of the Hep II domain increased cell
      spreading and the numbers of focal adhesions and stress fibers. Cell spreading
      and stress fiber formation were not mediated by heparan sulfate proteoglycans
      because treatment with chlorate, heparinase, or soluble heparin did not prevent
      Hep II domain-mediated cell spreading. Cell spreading and stress fiber formation
      were mediated by alpha4beta1 integrin because soluble anti-alpha4 integrin
      antibodies inhibited Hep II domain-mediated cell spreading and soluble vascular
      cell adhesion molecule-1 (alpha4beta1 ligand)-induced cell spreading. This is the
      first demonstration of the Hep II domain mediating cell spreading and stress
      fiber formation through alpha4beta1 integrin. This novel pathway demonstrates a
      cooperative, rather than antagonistic, role between alpha5beta1 and alpha4beta1
      integrins and suggests that interactions between the Hep II domain and
      alpha4beta1 integrin could modulate the strength of cytoskeleton-mediated
      processes in the trabecular meshwork of the human eye.

PMID- 15572367
TI  - Peptidomics of Cpe fat/fat mouse hypothalamus: effect of food deprivation and
      exercise on peptide levels.
AB  - Carboxypeptidase E is a major enzyme in the biosynthesis of numerous
      neuroendocrine peptides. Previously, we developed a technique for the isolation
      of neuropeptide-processing intermediates from mice that lack carboxypeptidase E
      activity (Cpe fat/fat mice) due to a naturally occurring point mutation. In the
      present study, we used a differential labeling procedure with stable isotopic
      tags and mass spectrometry to quantitate the relative changes in a number of
      hypothalamic peptides in Cpe fat/fat mice in two different paradigms that each
      cause an approximately 10% decrease in body mass. One paradigm involved a 2-day
      fast under normal sedentary conditions (i.e. standard mouse cages); the other
      involved giving mice access to an exercise wheel for 4 weeks with free access to
      food. Approximately 50 peptides were detected in both studies, and over 80
      peptides were detected in at least one of the two studies. Twenty-eight peptides
      were increased >50% by food deprivation, and some of these were increased by 2-
      to 3-fold. In contrast, only three peptides were increased >50% in the group with
      exercise wheels, and many peptides showed a slight 15-30% decrease upon exercise.
      Approximately one-half of the peptides detected in both studies were identified
      by tandem mass spectrometry. Peptides found to be elevated by food deprivation
      but not exercise included a number of fragments of proenkephalin, prothyrotropin
      releasing hormone, secretogranin II, chromogranin B, and pro-SAAS. Taken
      together, the differential regulation of these peptides in the two paradigms
      suggests that the regulation is not due to the lower body weight but to the
      manner in which the paradigms achieved this lower body weight.

PMID- 15572368
TI  - Unexpected side chain effects at residue 8 of cyclosporin a derivatives allow
      photoswitching of immunosuppression.
AB  - To dissect the enzyme inhibitory properties of the immunosuppressive cyclic
      undecapeptide cyclosporin A (CsA) and gain access to monospecific, non
      calcineurin-inhibiting CsA derivatives, [D-Ser8]CsA was subjected to
      modifications at the D-Ser side chain. Thus, we modified a CsA residue flanking
      the calcineurin (CaN) and cyclophilin 18 (Cyp18) binding domains of CsA instead
      of the residues of the CaN binding domain in order to develop a new specificity
      determining site within the cyclic peptide. The [O-(NH2 (CH2)5NHC(O)CH2)-D
      Ser8]CsA (derivative 9), with an amino group on a tether, exhibits CsA-like
      inhibition of the peptidyl prolyl cis/trans isomerase activity of Cyp18 with an
      IC50 value of 3.2 nm, whereas the CaN inhibition by the Cyp18-derivative 9
      complex is completely abolished. Consequently, this compound is not able to
      inhibit the proliferation and cytokine production of activated T cells. Structure
      activity relationship studies with a series of [d-Ser(8)]CsA derivatives indicate
      that the positively charged side chain is an essential requirement for Cyp18
      derivative 9 to be ineffective on CaN. Upon protecting the amino group in
      derivative 9 with the photolabile moiety 2-nitroveratryloxycarbonyl (NVOC), the
      Cyp18-[O-(NVOC-NH(CH2)5NHC(O)CH2)-D-Ser8]CsA (derivative 11) complex exhibits
      strong CaN inhibition and shows potent immunosuppressive activity. In stimulated
      T cells pretreated with derivative 11, a remarkable recovery of transcriptional
      activation of the nuclear factor of activated T cells (NFAT) has been achieved
      through light irradiation, as assessed with a NFAT reporter gene assay.

PMID- 15572369
TI  - Single amino acid mutations in the cadherin receptor from Heliothis virescens
      affect its toxin binding ability to Cry1A toxins.
AB  - Bacillus thuringiensis Cry protein exerts its toxic effect through a receptor
      mediated process. Both aminopeptidases and cadherin proteins were identified as
      putative Cry1A receptors from Heliothis virescens and Manduca sexta. The
      importance of cadherin was implied by its correlation with a Cry1Ac resistant H.
      virescens strain (Gahan, L. J., Gould, F., and Heckel, D. G. (2001) Science 293,
      857-860). In this study, the Cry1Ac toxin-binding region in H. virescens cadherin
      was mapped to a 40-amino-acid fragment, from amino acids 1422 to 1440. This site
      overlaps with a Cry1Ab toxin-binding site, amino acids 1363-1464 recently
      reported in M. sexta (Hua, G., Jurat-Fuentes, J. L., and Adang, M. J. (2004) J.
      Biol. Chem. 279, 28051-28056). Further, feeding of the anti-H. virescens cadherin
      antiserum or the partial cadherins, which contain the toxin-binding region, in
      combination with Cry1Ab/Cry1Ac reduced insect mortality by 25.5-55.6% to first
      instar H. virescens and M. sexta larvae, suggesting a critical function for this
      cadherin domain in insect toxicity. Mutations in this region, to which the Cry1Ac
      binds through its loop 3, resulted in the loss of toxin binding. For the first
      time, we show that the cadherin amino acids Leu(1425) and Phe(1429) are critical
      for Cry1Ac toxin interaction, and if substituted with charged amino acids, result
      in the loss of toxin binding, with a K(D) of < 10(-5) m. Mutation of Gln(1430) to
      an alanine, however, increased the Cry1Ac affinity 10-fold primarily due to an
      increase on rate. The L1425R mutant can result from a single nucleotide mutation,
      CTG --> CGG, suggesting that these mutants, which have decreased toxin binding,
      may lead to Cry1A resistance in insects.

PMID- 15572370
TI  - S100B increases proliferation in PC12 neuronal cells and reduces their
      responsiveness to nerve growth factor via Akt activation.
AB  - S100B is a Ca2+-modulated protein of the EF-hand type expressed in high abundance
      in a restricted set of cell types including certain neuronal populations. S100B
      has been suggested to participate in cell cycle progression, and S100B levels are
      high in tumor cells, compared with normal parental cells. We expressed S100B in
      the neuronal cell line PC12, which normally does not express the protein, by the
      Tet-Off technique, and found the following: (i) proliferation was higher in
      S100B+ PC12 cells than in S100B- PC12 cells; (ii) nerve growth factor (NGF),
      which decreased the proliferation of S100B- PC12 cells, was less effective in the
      case of S100B+ PC12 cells; (iii) expression of S100B made PC12 cells resistant to
      the differentiating effect of NGF; and (iv) interruption of S100B expression did
      not result in an immediate restoration of PC12 cell sensitivity to the
      differentiating effect of NGF. Expression of S100B in PC12 cells resulted in
      activation of Akt; increased levels of p21WAF1, an inhibitor of cyclin-dependent
      kinase (cdk) 2 and a positive regulator of cdk4; increased p21WAF1-cyclin D1
      complex formation; and increased phosphorylation of the retinoblastoma suppressor
      protein, Rb. These S100B-induced effects, as well as the reduced ability of
      S100B+ PC12 cells to respond to NGF, were dependent on Akt activation because
      they were remarkably reduced or abrogated in the presence of LY294002, an
      inhibitor of the Akt upstream kinase phosphatidylinositol 3-kinase. Thus, S100B
      might promote cell proliferation and interfere with NGF-induced PC12 cell
      differentiation by stimulating a p21WAF1/cyclin D1/cdk4/Rb/E2F pathway in an Akt
      mediated manner.

PMID- 15572371
TI  - The murine Cyp1a1 gene is expressed in a restricted spatial and temporal pattern
      during embryonic development.
AB  - In adult mice the cytochrome P450 Cyp1a1 gene is not constitutively expressed but
      is highly inducible by foreign compounds acting through the aryl hydrocarbon (Ah)
      receptor. However, the expression profile of the Cyp1a1 gene in the developing
      embryo is not well under-stood. Using established transgenic mouse lines where
      8.5 kb of the rat CYP1A1 promoter is cloned upstream of the lacZ reporter gene
      (1), we describe the expression of the CYP1A1-driven reporter gene in all tissues
      through-out stages E7-E14 of embryonic development. In contrast to the absence of
      constitutive Cyp1a1 and lacZ transgene expression in tissues of the adult mouse,
      a constitutive cell-specific and time-dependent pattern of CYP1A1 promoter
      activity was observed in the embryo. This expression pattern was confirmed as
      reflecting the endogenous gene by measuring Cyp1a1 mRNA levels and protein
      expression by immunohistochemistry. The number of cells displaying endogenous
      CYP1A1 activity could be increased in the embryo upon xenobiotic challenge, but
      only within areas where the CYP1A1 promotor was already active. When reporter
      mice were bred onto a genetic background expressing a lower affinity form of the
      Ah receptor (DBA allele), transgene and murine Cyp1a1 protein expression were
      both attenuated in the adult mouse liver upon xenobiotic challenge. By
      comparison, constitutive CYP1A1 promoter activity in the embryo was identical in
      the presence of either the high or low affinity Ah receptor. These novel data
      suggest that the Cyp1a1 protein may play a role in murine development and that
      regulation of the Cyp1a1 gene during this period is either through the action of
      a high affinity Ah receptor ligand or by an alternative regulatory pathway.

PMID- 15572372
TI  - AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene
      expression in hepatocytes and a newly derived human hepatoma cell line.
AB  - Phenobarbital (PB) administration is known to trigger pleiotropic responses,
      including liver hypertrophy, tumor promotion, and induction of genes encoding
      drug-metabolizing enzymes. The induction of human CYP2B6 and the rat (CYP2B1) and
      mouse (Cyp2b10) homologues by PB is mediated by the nuclear receptor constitutive
      androstane receptor (CAR). The study of CYP2B gene regulation and CAR activity by
      PB has been difficult due to the lack of a cellular model. In this study, we
      describe a novel differentiated human hepatoma cell line (WGA), derived from
      HepG2, which expresses CYP2B6 and CAR. WGA cells represent a powerful system to
      study the regulation of CYP2B6 gene expression by PB. There is evidence that CAR
      activity is regulated by phosphorylation and that regulation of some CYP genes
      depends on the nutritional status of cells. The AMP-activated protein kinase
      (AMPK) functions as an energy sensor and is activated when cells experience
      energy-depleting stresses. In this report, we show that addition of 5-amino
      imidazole carboxamide riboside, an AMPK activator, to WGA and human hepatocytes
      induces CYP2B6 gene expression. Expression of a constitutively active form of
      AMPK mimics the PB induction of CYP2B6 and CYP2B1 gene expression. Conversely,
      the expression of a dominant negative form of AMPK inhibits the induction of
      these genes by PB. Finally, we demonstrate, for the first time, that AMPK
      activity increases in cells cultured with PB. Our data strongly support a role
      for AMPK in the PB induction of CYP2B gene expression and provide new insights
      into the regulation of gene expression by barbiturate drugs.

PMID- 15572373
TI  - Mechanistic roles of Ser-114, Tyr-155, and Lys-159 in 3alpha-hydroxysteroid
      dehydrogenase/carbonyl reductase from Comamonas testosteroni.
AB  - 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from
      Comamonas testosteroni, a short chain dehydrogenase/reductase, catalyzes the
      oxidation of androsterone with NAD+ to form androstanedione and NADH. A catalytic
      triad of Ser-114, Tyr-155, and Lys-159 in 3alpha-HSD/CR has been proposed based
      on structural analysis and sequence alignment of the short chain
      dehydrogenase/reductase family. The 3alpha-HSD/CR-catalyzed reaction has not been
      kinetically analyzed in detail, however. In this study, we combined steady-state
      kinetics, site-directed mutagenesis, and pH profile to explore the function of
      Ser-114, Tyr-155, and Lys-159 in 3alpha-HSD/CR-catalyzed reaction. The catalytic
      efficiency of wild-type and mutants S114A, Y155F, K159A, and Y155F/K159A is 4.3 x
      10(7), 7.3 x 10(4), 1.7 x 10(4), 2.4 x 10(5), and 71 m(-1)s(-1), respectively.
      The values of pKa on kcat/Km for the wild-type, S114A, Y155F, K159A, and
      Y155F/K159A are 7.2, 7.4, 8.4, 9.1, and 10.2, respectively. Mutant S114A/Y155F
      exhibits a pH-independent profile with 10(-5) times of wild-type activity at pH
      10.5. The activity decreases as the pH lowers, which indicates that a functional
      group with an apparent pKa of 7.2 is involved in the general base catalysis for
      wild-type 3alpha-HSD/CR. The pKa shift to 9.1 for mutant K159A suggests the role
      of Lys-159 is to lower the pKa of the residues involved in the general base
      catalysis. Because pH dependence is observed for both S114A and Y155F mutants and
      pH independence is observed in S114A/Y155F, Tyr-155 may be important as a general
      base catalysis in the wild-type, whereas Ser-114 may act as a general base on
      mutant Y155F to catalyze the reaction.

PMID- 15572374
TI  - ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for
      transcriptional activation and protein degradation.
AB  - The ultimate carcinogen and metabolite of benzo-[a]pyrene-7,8-dihydrodiol,
      benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (+/-), stimulates apoptosis,
      and this process can be blocked by extracellular signal-regulated kinase (Erk)
      kinase inhibitors. However, we show here that Erk kinase inhibitors were unable
      to prevent B[a]P-7,8-dihydrodiol-induced apoptosis, leading us to speculate that
      Erk kinases are linked to regulation of the aryl hydrocarbon (Ah) receptor.
      Cotreatment of hepa1c1c7 cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      and Erk kinase inhibitor PD98059, U0126, or SL327 led to enhanced nuclear
      accumulation of Ah receptor but with a reduced capacity to complement TCDD
      induction of Cyp1a1. This is explained in part by the ability of Erk kinase
      inhibitors to alter the steady-state levels of cellular Ah receptor, a result
      that leads to a dramatic induction in detectable receptor levels. These changes
      in cellular Ah receptor levels are associated with delayed degradation of the Ah
      receptor because TCDD-initiated degradation is reversed when cells are co-treated
      with TCDD and Erk kinase inhibitors. Erk kinase is linked to Ah receptor
      expression, as demonstrated by reductions in total Ah receptor levels after
      overexpression of constitutively active MEK1. In addition, Erk kinase activity
      modulates the transcriptional response because MEK1 overexpression enhances TCDD
      initiated transactivation potential of the receptor. Thus, Erk kinase activity
      facilitates ligand-initiated transcriptional activation while targeting the Ah
      receptor for degradation. Immunoprecipitation experiments of the Ah receptor
      indicate that Erk kinase activity is associated with the receptor. It is
      interesting that the carboxyl region of the Ah receptor is associated with the
      transactivation region as well as the site for ubiquitination, indicating that
      Erk kinase-dependent phosphorylation targets the carboxyl region of the receptor.

PMID- 15572375
TI  - An intact DNA-binding domain is not required for peroxisome proliferator
      activated receptor gamma (PPARgamma) binding and activation on some PPAR response
      elements.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) interacts with
      retinoid X receptor (RXR) on PPAR response elements (PPREs) to regulate
      transcription of PPAR-responsive genes. To investigate the binding of PPARgamma
      and RXR to PPREs, three mutations were constructed in the DNA-binding domains of
      PPARgamma; two of the mutants maintained the structure of zinc finger I
      (PPARgamma-GS and PPARgamma-AA), and a third mutation disrupted the protein
      structure of zinc finger I (PPARgamma-CS). Results indicated that the mutations
      of PPARgamma that maintained intact zinc fingers were capable of binding to a
      variety of PPREs in the presence of RXR and could activate transcription on
      several PPREs. In parallel, a mutation was created in the DNA-binding domain of
      RXRalpha that maintained the structure of the zinc fingers (RXR-GS) but did not
      bind DNA and was transcriptionally inactive. Examination of the 3' half-site of
      several PPREs revealed that variations from the consensus sequence reduced or
      abolished transcriptional activity, but conversion to consensus improved
      transcriptional activity with PPARgamma-GS and PPARgamma-AA. Examination of the
      5' half-site indicated that the upstream three nucleotides were more important
      for transcriptional activity than the downstream three nucleotides. Our data
      demonstrated that stringent binding of RXR to the 3' half-site of a PPRE is more
      influential on the binding of the PPARgamma/RXR heterodimer than the ability of
      PPARgamma to bind DNA. Thus, unlike RXR, PPARgamma exhibits promiscuity in
      binding on a PPRE, suggesting that the definition of a PPRE for PPARgamma may
      need to be expanded.

PMID- 15572376
TI  - Amino acids important for ligand specificity of the human constitutive androstane
      receptor.
AB  - The human constitutive androstane receptor (CAR, NR1I3) is an important ligand
      activated regulator of oxidative and conjugative enzymes and transport proteins.
      Because of the lack of a crystal structure of the ligand-binding domain (LBD),
      wide species differences in ligand specificity and the scarcity of well
      characterized ligands, the factors that determine CAR ligand specificity are not
      clear. To address this issue, we developed highly defined homology models of
      human CAR LBD to identify residues lining the ligand-binding pocket and to
      perform molecular dynamics simulations with known human CAR modulators. The roles
      of 22 LBD residues for basal activity, ligand selectivity, and interactions with
      co-regulators were studied using site-directed mutagenesis, mammalian co
      transfection, and yeast two-hybrid assays. These studies identified several amino
      acids within helices 3 (Asn(165)), 5 (Val(199)), 11 (Tyr(326), Ile(330), and
      Gln(331)), and 12 (Leu(343) and Ile(346)) that contribute to the high basal
      activity of human CAR. Unique residues within helices 3 (Ile(164) and Asn(165)),
      5 (Cys(202) and His(203)), and 7 (Phe(234) and Phe(238)) were found control the
      selectivity for CAR activators and inhibitors. A single residue in helix 7
      (Phe(243)) appears to explain the human/mouse species difference in response of
      CAR to 17alpha-ethynyl-3,17beta-estradiol.

PMID- 15572377
TI  - Parsing ERK activation reveals quantitatively equivalent contributions from
      epidermal growth factor receptor and HER2 in human mammary epithelial cells.
AB  - HER2, a member of the epidermal growth factor receptor (EGFR) tyrosine kinase
      family, functions as an accessory EGFR signaling component and alters EGFR
      trafficking by heterodimerization. HER2 overexpression leads to aberrant cell
      behavior including enhanced proliferation and motility. Here we applied a
      combination of computational modeling and quantitative experimental studies of
      the dynamic interactions between EGFR and HER2 and their downstream activation of
      ERK to understand this complex signaling system. Using cells expressing different
      levels of HER2 relative to the EGFR, we could separate relative contributions of
      EGFR and HER2 to signaling amplitude and duration. Based on our model
      calculations, we demonstrated that, in contrast with previous suggestions in the
      literature, the intrinsic capabilities of EGFR and HER2 to activate ERK were
      quantitatively equivalent. We found that HER2-mediated effects on EGFR
      dimerization and trafficking were sufficient to explain the observed HER2
      mediated amplification of epidermal growth factor-induced ERK signaling. Our
      model suggests that transient amplification of ERK activity by HER2 arises
      predominantly from the 2-to-1 stoichiometry of receptor kinase to bound ligand in
      EGFR/HER2 heterodimers compared with the 1-to-1 stoichiometry of the EGFR
      homodimer, but alterations in receptor trafficking yielding increased EGFR
      sparing cause the sustained HER2-mediated enhancement of ERK signaling.

PMID- 15572379
TI  - A novel role for vascular endothelial growth factor as an autocrine survival
      factor for embryonic stem cells during hypoxia.
AB  - Vascular endothelial growth factor (VEGF) is best known for its angiogenic
      activity on endothelial cells, but it also affects neurons, pneumocytes, and
      other mature cell types as well as endothelial, neural, and hematopoietic
      progenitors. Here, we examined its effect on pluripotential embryonic stem (ES)
      cells under hypoxic stress. ES cells were found to produce VEGF and to express
      VEGF receptor-2 and neuropilin-1 (Nrp-1), a VEGF165 isoform-specific receptor.
      During hypoxia, expression levels of VEGF, Flk-1, and Nrp-1 were elevated.
      Inhibition or targeted gene inactivation of VEGF increased ES cell apoptosis
      during prolonged hypoxia (48 h) by about 10-fold. The survival activity of VEGF
      was specific since inhibition of other growth factors (including basic fibroblast
      growth factor, epidermal growth factor, insulin-like growth factor, platelet
      derived growth factor, and placental growth factor) had no effect. Neuropilin-1
      was involved in the VEGF-survival activity since overexpression of Nrp-1
      decreased hypoxia-induced apoptosis about 3-fold. The hypoxia-response element,
      via which hypoxia-inducible transcription factors up-regulate VEGF expression
      under hypoxic conditions, was critical since targeted deletion of this element in
      the VEGF promoter enhanced hypoxia-induced ES cell apoptosis to the same extent
      as VEGF inhibition or gene inactivation. Thus, VEGF plays a critical role in
      survival of ES cells during prolonged hypoxia.

PMID- 15572378
TI  - E1A activates transcription of p73 and Noxa to induce apoptosis.
AB  - p73, a member of the p53 family of proteins, transcriptionally activates a number
      of genes involved in the control of cell cycle and apoptosis. Overexpression of
      p73 was detected in a large number of primary head and neck cancers, and in the
      established cell lines examined, these all contained inactivating p53 mutations.
      The significance of p73 overexpression in the pathogenesis of head and neck
      cancer is currently unclear. We have shown that the expression of adenovirus 5
      E1A in a panel of head and neck cancer cell lines induces apoptosis independently
      of their p53 status. In this study we examined the role of p73 and its
      transcriptional targets in E1A-mediated induction of apoptosis. E1A expression
      resulted in significant activation of the TAp73 promoter but had no effect on the
      alternative, DeltaNp73 promoter. E1A also increased expression of endogenous
      TAp73 mRNA and protein. E1A mutants lacking the p300- and/or pRB-binding sites
      showed reduced ability to activate the TAp73 promoter. Additionally, mutations in
      the E2F1-binding sites in the TAp73 promoter impaired activation by E1A.
      Importantly, expression of the 13S isoform of E1A substantially induced the p53
      apoptotic target Noxa in several p53-deficient cancer cell lines. Our results
      indicate that E1A activation of p73 and the p53 apoptotic target Noxa can occur
      in the absence of a functional p53. This activation is likely to play a key role
      in the mechanism of p53-independent apoptosis induced by E1A in some cancers and
      may provide an avenue for future cancer therapies.

PMID- 15572380
TI  - The end of the beginning: patient safety five years after 'to err is human'.
AB  - The Institute of Medicine's 1999 report on medical errors galvanized the public
      and health professionals. Before then, providers, health care organizations, and
      policymakers lacked the understanding and incentives to generate the changes in
      culture, systems, training, and technology to improve safety. Since 1999 there
      has been progress, but it has been insufficient. Stronger regulation has helped,
      as have some early improvements in information technology and in workforce
      organization and training. Error-reporting systems have had little impact, and
      scant progress has been made in improving accountability. Five years after the
      report's publication, we appear to be at "the end of the beginning".

PMID- 15572381
TI  - Transplanting kidneys from CMV-seropositive donors to CMV-seronegative recipients
      is not associated with poorer renal allograft function or survival.
AB  - BACKGROUND: Cytomegalovirus (CMV)-seronegative recipients of renal allografts
      from CMV-seropositive donors (D+/R-) have a higher rate of acute rejection than
      other renal transplant recipients. A relationship between CMV infection/disease
      and chronic allograft nephropathy (CAN) has been proposed from animal studies,
      although human studies have been inconclusive. The objective of this study was to
      determine if CMV seromatching has an effect on renal allograft function and
      allograft survival. METHODS: A retrospective single centre study was carried out
      in 333 first cadaveric transplant recipients from January 1, 1991 to December 31,
      1997. The primary end-point was creatinine clearance at 3 years post-transplant
      in groups based on CMV seromatching. The secondary end-point was renal allograft
      survival. RESULTS: Mean creatinine clearance 3 years post-transplant was 53.4
      ml/min/1.73 m2 of body surface area. There was no significant difference in the
      mean creatinine clearance for groups formed on the basis of CMV seromatching.
      Delayed graft function and acute rejection were associated with a lower
      creatinine clearance at 3 years and reduced overall graft survival [hazard ratios
      2.35 (1.56-3.54) (P<0.001) and 1.57 (1.0-2.46) (P = 0.046), respectively].
      Considering the end-point of graft loss due to acute rejection (censoring for
      death with a functioning graft) identified the D+/R- group as having an increased
      hazard of graft loss due to acute rejection [hazard ratio 3.12 (1.16-8.57) (P =
      0.024)]. CONCLUSIONS: The D+/R- group does not appear to have poorer renal
      allograft function 3 years post-transplant. This group does, however, have an
      increased risk of early allograft loss due to acute rejection.

PMID- 15572382
TI  - Uric acid correlates with the severity of histopathological parameters in IgA
      nephropathy.
AB  - BACKGROUND: Immunoglobulin-A nephropathy (IgAN) is the most common chronic
      glomerulonephritis worldwide. Many clinical and histopathological risk factors
      for progression have been found previously. Recently, metabolic risk factors,
      such as hyperuricaemia and hypertriglyceridaemia, also have been associated with
      the progression of IgAN. METHODS: In the present study we correlated clinical and
      metabolic risk factors with histopathological parameters in 202 patients with
      IgAN. Morphological changes in glomerular, tubulointerstitial and vascular tissue
      were semiquantitatively graded into three classes. Mesangial proliferation
      activity and the amount of inflammatory cells were also evaluated by
      immunohistochemical staining of Ki-67 (MIB-1), CD45 (LCA) and CD68 stainings.
      Serum uric acid, triglycerides and cholesterol, urine protein excretion (UPE),
      blood pressure and body mass index (BMI) were measured. Smoking habits and
      occurrence of diabetes mellitus also were evaluated. The independent role of
      serum uric acid in the development of renal morphological changes was evaluated
      in multivariate analysis. RESULTS: Serum uric acid and UPE level correlated with
      several histological parameters. Uric acid level showed the strongest correlation
      with tubulointerstitial changes and UPE with glomerulosclerosis. The level of
      serum triglycerides correlated with interstitial fibrosis and hyaline
      arteriolosclerosis. Blood pressure correlated with hyaline arteriolosclerosis,
      glomerulosclerosis and tubulointerstitial changes. BMI and diabetes mellitus
      correlated with both tubulointerstitial and vascular changes. We found no
      significant correlations between histopathological parameters and smoking habits
      or serum cholesterol level. Serum uric acid had independent associations with the
      presence of tubular atrophy and interstitial fibrosis and inflammation.
      CONCLUSIONS: We conclude that many metabolic factors are univariately associated
      with renal morphological findings in IgAN. These same factors are central in the
      metabolic or insulin resistance syndrome and may have a pathogenetic role in the
      progression of IgAN. Serum uric acid may have an independent role in development
      of tubulointerstitial lesions as well as being associated with inflammation in
      renal tissue of patients with IgAN.

PMID- 15572383
TI  - Individual differences in renal ACE activity in healthy rats predict
      susceptibility to adriamycin-induced renal damage.
AB  - BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels,
      related to ACE (I/D) genotype, are associated with renal prognosis. This raises
      the hypothesis that individual differences in renal ACE activity are involved in
      renal susceptibility to inflicted damage. Therefore, we studied the predictive
      effect of renal ACE activity for the severity of renal damage induced by a single
      injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu
      cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male
      Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5
      mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was
      measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys
      harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range
      proteinuria, renal interstitial damage and mild focal glomerulosclerosis.
      Baseline renal ACE positively correlated with the relative rise in proteinuria
      after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin
      (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05),
      interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle
      actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal
      ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls,
      no predictive values for renal parameters were observed. CONCLUSION: Individual
      differences in renal ACE activity predict the severity of adriamycin-induced
      renal damage in this outbred rat strain. This supports the assumption that
      differences in renal ACE activity predispose to a less favourable course of renal
      damage.

PMID- 15572384
TI  - Development and validation of an immunosuppressant therapy adherence barrier
      instrument.
AB  - BACKGROUND: To decrease allograft rejection as a result of non-adherence to
      immunosuppressant therapy (IST), a valid and reliable instrument that measures
      solid organ transplant patients' adherence barriers is needed. METHODS: An
      immunosuppressant therapy barrier scale (ITBS) was developed to assess transplant
      patients' perceived barriers to IST adherence and was completed by 222 transplant
      patients who lived in Georgia, USA. A renal transplant population subset was used
      to test the ITBS reliability and validity. Scale reliability was estimated using
      Cronbach's alpha coefficient of internal consistency; scale dimensionality was
      assessed using principal components analysis. The criterion-related validity of
      the scale was assessed by relating subscale scores to adherence measures and
      graft rejection. Nomological validity was assessed by relating barrier subscales
      to specific patient factors. RESULTS: Two subscales that represented
      'controllable' and 'uncontrollable' barriers were found. Cronbach's alpha
      coefficients demonstrated acceptable reliabilities of 0.93, 0.86 and 0.91 for the
      'uncontrollable' and 'controllable' subscales, and for the entire ITBS,
      respectively. The ITBS subscales correlated negatively with a self-reported
      measure of IST adherence, IST serum concentrations and IST pharmacy refill
      adherence rate (P<0.01). The 'uncontrollable barrier' subscale was positively
      correlated to kidney graft rejection (P<0.01), thus demonstrating the ITBS's
      validity. Males and older patients reported more adherence barriers (P<0.05).
      CONCLUSIONS: The ITBS is a reliable and valid instrument that can be used to
      measure patients' perceived barriers to IST adherence.

PMID- 15572385
TI  - Peritoneal dialysis fluid-induced changes of the peritoneal membrane are
      reversible after peritoneal rest in rats.
AB  - BACKGROUND: Peritoneal dialysis (PD) is associated with functional and structural
      alterations of the peritoneal membrane. However, the (ir)reversibility of these
      pathological changes of the peritoneum is not understood fully. METHODS: In an
      experimental PD model, rats (n = 15) received daily 10 ml conventional glucose
      containing PD fluid, via peritoneal catheters connected to implanted subcutaneous
      mini vascular access ports. After 5 weeks of treatment, the first group of
      animals (PDF; n = 10) was sacrificed, while peritoneal catheters of the remaining
      group of rats (PD-rest; n = 5) were removed 1 week later. The latter group (PD
      rest) was sacrificed 12 weeks after removing catheters. At both time points,
      untreated rats were included as controls. Cellular and morphological parameters
      were analysed by light and electron microscopy. RESULTS: Rats exposed to PD fluid
      for 5 weeks showed a severe angiogenesis in various peritoneal tissues.
      Peritoneal rest resulted in a significant reduction in blood vessel density in
      visceral (mesentery, P<0.05), but not in parietal peritoneum. Five weeks'
      exposure to PD fluid resulted in a profound fibrosis in the parietal peritoneum,
      whereas the degree of fibrosis was significantly reduced in the PD-rest group
      (P<0.02). Daily exposure to PD fluid induced a higher number of mast cells in the
      omentum compared with untreated rats, whereas peritoneal rest normalized the
      increased mast cell density completely (P<0.03). Likewise, continued PD fluid
      instillation evoked a strong omental milky spot response, which was returned to
      the control level after peritoneal rest (P<0.009). Furthermore, the number of
      mesothelial cells on the liver was significantly increased in rats treated with
      PD fluid, whereas animals from the PD-rest group had a lower number of
      mesothelial cells, although this was not statistically significant (P = 0.08).
      Finally, as evidenced by electron microscopy, daily exposure to PD fluid resulted
      in severe damage to the mesothelial cell layer covering the peritoneum, whereas
      this cell layer was completely recovered after peritoneal rest. CONCLUSIONS: We
      show that PD fluid-induced cellular and morphological alterations of the
      peritoneal membrane are generally reversible.

PMID- 15572386
TI  - Factors associated with increased plasma homocysteine in patients using an amino
      acid peritoneal dialysis fluid.
AB  - BACKGROUND: Although amino acid peritoneal dialysate (AAPD) substitution is
      thought to improve protein-energy malnutrition in patients undergoing peritoneal
      dialysis (PD), it may also increase plasma homocysteine (Hcy) levels due to the
      methionine load in the dialysate. However, it is still unclear which factors are
      important for elevating Hcy in patients treated with AAPD. METHODS: Sixteen
      malnourished PD patients (age 48+/-18 years) were treated daily with one exchange
      of 1.1% AAPD for 3 months. The effects of AAPD on nutrition, Hcy, methionine,
      leptin and insulin resistance were studied. We also analysed factors that
      influenced plasma Hcy levels. RESULTS: We found a transient increase in serum
      albumin (P<0.01) after 1 month treatment, especially in patients with serum
      albumin < or = 3.5 g/dl. Total plasma Hcy increased markedly after AAPD (the peak
      at month 2, P<0.001) and returned to baseline after ceasing AAPD, despite no
      changes in dietary methionine intake and serum methionine levels. Eight patients
      with Hcy increments >5.65 microM (the median) had lesser dietary intakes of
      protein (P = 0.01) and methionine (P = 0.028), lower body fat mass (P = 0.05) and
      lower aspartate transaminase (AST) (P = 0.008) before AAPD treatment than
      patients with lower increments. DeltaHcy was inversely correlated with baseline
      dietary methionine intake (r = -0.61), protein intake (r = -0.54) and AST (r = 
      0.51) (all P<0.05). There was no change in leptin or insulin resistance. AAPD
      treatment significantly increased Kt/Vurea (P<0.001), weekly creatinine clearance
      (P<0.05) and peritoneal glucose transport (P<0.05). CONCLUSIONS: Treatment with
      1.1% AAPD transiently increased serum albumin in malnourished PD patients.
      However, the methionine load from the dialysate in this study significantly
      elevated plasma Hcy levels, especially in patients with lower protein and
      methionine intakes, and lower AST levels. Further long-term studies will be
      needed to clarify potential nutritional benefits and adverse effects of AAPD.

PMID- 15572387
TI  - Atherosclerotic risk factors and renal function in the elderly: the role of
      hyperfibrinogenaemia and smoking. Results from the Italian Longitudinal Study on
      Ageing (ILSA).
AB  - BACKGROUND: We examined associations between cardiovascular diseases and risk
      factors with pathological levels of and significant changes in serum creatinine
      (SCr) in a large prevalence phase and longitudinal phase community-based sample
      of an elderly Italian population (ILSA Study) showing no clinical evidence of
      renal impairment. METHODS: The prevalence phase was performed on 2981 subjects,
      aged 65-84 years, who were negative for renal diseases, had available SCr values
      and had complete clinical information on their cardiovascular risk factors. Of
      these, 371 were considered 'healthy' since they were not affected by
      cardiovascular diseases or diabetes, whereas 2610 tested positive for
      cardiovascular diseases and were considered 'diseased'. The sex-specific 95th
      percentiles for SCr (cut-off points) were calculated in the healthy reference
      sample to define the upper limit for normal SCr values. The distribution and
      prevalence of diseased subjects having values over the cut-off point values were
      then estimated. Associations between values over the cut-off point levels and
      pathological or clinical conditions were analysed from the diseased sample. The
      longitudinal phase was carried out on 1906 subjects who had SCr values and
      sufficient clinical information for our investigation. The incidence of an
      increase of >26.5 micromol/l of SCr was evaluated in the longitudinal cohort.
      RESULTS: In healthy subjects, the 95th SCr percentiles (cut-off points) were
      123.8 micromol/l in men and 97.2 micromol/l in women. In diseased subjects, the
      prevalence of SCr values over the cut-off point was 4.6% in men and 9.3% in
      women. In logistic regression analysis, independent variables that correlated
      with over the cut-off point SCr values were: age >75 years [odds ratio (OR) =
      2.2; 95% confidence interval (CI) = 1.5-3.4], atherosclerosis of the lower limbs
      (OR = 2.0; 95% CI = 1.2-3.3), cerebrovascular disease (OR = 1.9; 95% CI = 1.2
      3.3), angiotensin-converting enzyme (ACE) inhibitor medication (OR = 1.8; 95% CI
      = 1.2-2.8), fibrinogen values >3.5 g/l (OR = 1.2; 95% CI = 1.2-2.7) and diuretic
      treatment (OR = 1.6; 95% CI = 1.1-2.4). After a mean 3.6 years follow-up,
      multiple logistic regression analysis showed that risk factors for pathological
      loss of renal function (rise of SCr >26.5 micromol/l) were: current smokers >20
      cigarettes/day (OR = 2.3; 95% CI = 1.0-5.3), fibrinogen values >3.5 g/l (OR =
      2.2; 95% CI = 1.6-3.3), diabetes (OR = 1.8; 95% CI = 1.1-2.8), age >75 years (OR
      = 1.7; 95% CI = 1.2-2.4) and isolated systolic hypertension (OR = 1.6; 95% CI =
      1.0-2.6). The loss of renal function examined during the longitudinal phase
      appeared to be independent of baseline SCr levels. CONCLUSION: The present
      prevalence and longitudinal studies show that age-associated decline in renal
      function in elderly subjects is associated with co-existing cardiovascular
      diseases and risk factors. These observations should be incorporated into
      clinical practice since some of the factors detrimental to kidney function, such
      as smoking, altered fibrinogen levels and elevated systolic blood pressure, can
      be prevented and/or modified when appropriate measures are taken.

PMID- 15572388
TI  - Renal artery stenosis in hypertensive patients with antiphospholipid (Hughes)
      syndrome: outcome following anticoagulation.
AB  - OBJECTIVE: We have demonstrated a point prevalence of 26% renal artery stenosis
      in patients with antiphospholipid syndrome (APS) and uncontrolled hypertension.
      We describe the effect of anticoagulation on blood pressure control and renal
      function. METHODS: We studied 23 patients retrospectively with renal artery
      stenosis (RAS). Fourteen received oral anticoagulation for more than 1 yr (target
      International Normalized Ratio (INR) of 3.0-4.5). Five patients had primary APS.
      Patients were divided into two groups based on their INR (< 3.0 and > or = 3.0).
      Nine patients had repeat magnetic resonance angiography (MRA) or an angiogram of
      the renal arteries after 2 yr. RESULTS: Only 8/14 patients managed to maintain
      their INR > or = 3.0 (median INR 3.1, range 2.8-3.7) while six had a INR < 3.0
      (median INR 1.9, range 1.2-2.4). Patients with a median INR < 3.0 had poorly
      controlled blood pressure and there was significant deterioration in mean serum
      creatinine values (Wilcoxon's test, P < 0.03). Nine patients underwent follow-up
      renal artery imaging. Three of nine patients with an INR < 3.0 (median INR 1.9)
      had re-stenosis and a fourth developed bilateral renal artery stenosis. Five
      patients with INR > or = 3.0 (median INR 3.1) did not show re-stenosis of the
      renal arteries; their renal function was stable and blood pressure was well
      controlled. One other patient with secondary APS (mixed connective tissue
      disorder) with INR > 3.0 showed recanalization of the stenosed renal artery.
      CONCLUSION: Anticoagulation with INR maintained > or = 3.0 helped to control the
      blood pressure and prevent the progression of renal disease.

PMID- 15572389
TI  - Mycophenolate mofetil (CellCept): an alternative therapy for autoimmune
      inflammatory myopathy.
AB  - OBJECTIVES: Mycophenolate mofetil (MMF) is a new immunosuppressive agent
      currently being used for the prevention of renal allograft rejection. MMF is a
      specific inhibitor of lymphocytes and is well tolerated leading to its use in
      other autoimmune diseases. We have used MMF for the treatment of seven patients
      with inflammatory myopathy and are hereby reporting our results. CASE SERIES: All
      of our patients were females (age 17-65 yr). They were symptomatic upon
      presentation and met classification criteria for idiopathic inflammatory
      myopathy. Inflammatory markers such as erythrocyte sedimentation rate and C
      reactive protein as well as creatine kinase were significantly elevated in all
      the patients, indicating active disease. Corticosteroids were concomitantly being
      administered (20-60 mg/day of prednisone). Initial therapy with conventional
      immunosuppressives was either ineffective or had significant adverse effects
      leading to their discontinuation. MMF was started in doses of 500 mg twice a day
      and titrated up to 1 g twice a day. RESULTS: Our patients have exhibited an
      impressive serological response to therapy with MMF and six patients had a marked
      improvement in their weakness. One patient had incomplete improvement in her
      weakness and has required additional therapies. MMF has been well tolerated
      during the treatment period (12-36 months). CONCLUSION: A striking clinical and
      laboratory response of active myositis in six out of seven patients in this
      series illustrates that MMF can be effectively used in management of autoimmune
      inflammatory myopathy and may be a suitable alternative to the conventional
      immunosuppressive agents.

PMID- 15572390
TI  - Accessibility, nature and quality of health information on the Internet: a survey
      on osteoarthritis.
AB  - OBJECTIVES: This study aims to determine the quality and validity of information
      available on the Internet about osteoarthritis and to investigate the best way of
      sourcing this information. METHODS: Keywords relevant to osteoarthritis were
      searched across 15 search engines representing medical, general and meta-search
      engines. Search engine efficiency was defined as the percentage of unique and
      relevant websites from all websites returned by each search engine. The quality
      of relevant information was appraised using the DISCERN tool and the concordance
      of the information offered by the website with the available evidence about
      osteoarthritis determined. RESULTS: A total of 3443 websites were retrieved, of
      which 344 were identified as unique and providing information relevant to
      osteoarthritis. The overall quality of website information was poor. There was no
      significant difference between types of search engine in sourcing relevant
      information; however, the information retrieved from medical search engines was
      of a higher quality. Fewer than a third of the websites identified as offering
      relevant information cited evidence to support their recommendations.
      CONCLUSIONS: Although the overall quality of website information about
      osteoarthritis was poor, medical search engines may provide consumers with the
      opportunity to source high-quality health information on the Internet. In the era
      of evidence-based medicine, one of the main obstacles to the Internet reaching
      its potential as a medical resource is the failure of websites to incorporate and
      attribute evidence-based information.

PMID- 15572391
TI  - Effect of experimentally induced knee pain on standing balance in healthy older
      individuals.
AB  - OBJECTIVE: Standing balance is impaired in older individuals with knee pain. The
      extent to which this impairment is due to the effects of pain itself or other
      pathophysiological aspects related to the underlying musculoskeletal condition
      causing the pain is unclear. To isolate the influence of pain, this study
      evaluated the effect of experimentally induced knee pain on standing balance in
      healthy older individuals. METHODS: We used a repeated-measures, within-subject
      design involving 12 healthy individuals aged 50-60 yr and with no history of knee
      pathology. Balance was tested during two randomly allocated experimental
      conditions: (i) control and (ii) knee pain induced by injection of hypertonic
      saline into the infrapatellar fat pad. Balance was measured using a computerized
      force platform under static and dynamic conditions as well as via the functional
      step test. RESULTS: Standing balance was not significantly altered by
      experimentally induced acute knee pain, nor was there any relationship between
      the severity of reported pain and balance scores. CONCLUSIONS: Impairments in
      balance associated with knee conditions such as osteoarthritis may be due to
      factors other than the sensation of pain. Thus, strategies designed to reduce
      pain in treatment of knee pathology may not necessarily lead to improvements in
      balance. Further research is required to determine the exact causes of balance
      impairment in individuals with knee joint pain and pathology.

PMID- 15572392
TI  - HLA allelic variants encoding DR11 in diffuse and limited systemic sclerosis in
      Caucasian women.
AB  - OBJECTIVE: We investigated HLA class II alleles in women with systemic sclerosis
      (SSc), a rare disease that preferentially affects women. METHODS: Specific
      alleles of DRB1, DQA1 and DQB1 were determined by DNA-based HLA typing for women
      with SSc (n = 102) and healthy women (n = 533). All study subjects were
      Caucasian. DRB1, DQA1 and DQB1 allele frequencies of women with SSc were compared
      with those of healthy women. RESULTS: Among women with SSc, 29.4% (30/102) and
      among healthy women 10.7% (57/533) had DRB1*11. Allele frequencies were compared
      for women with SSc and healthy women (each woman has two alleles). The allele
      frequency of DRB1*11 was 15.7% (32/204 alleles) in SSc women and 5.8% (62/1066
      alleles) in healthy women (P = 0.000002). The increase of DRB1*11 was found both
      in diffuse (P = 0.0001) and limited SSc (P = 0.002) (allele frequencies 15.0 and
      17.2%, respectively). Among women with diffuse SSc, there was a disproportionate
      increase of the DRB1*1104 allele (P = 0.0004) with no increase of DRB1*1101 (P =
      1.00). In contrast, in limited SSc the strongest association was with DRB1*1101
      (P = 0.008), with a less significant increase of DRB1*1104 (P = 0.04).
      CONCLUSIONS: An increase of DRB1*11 in SSc is consistent with other reports.
      Although present in both diffuse and limited SSc disease subsets, the increase
      was predominantly due to over-representation of DRB1*1104 in women with diffuse
      SSc. Women with limited SSc had a preponderance of DRB1*1101, the most common
      allele in healthy women. DRB1*1104 and DRB1*1101 differ by a single amino acid at
      position 86, where the former has valine and the latter glycine.

PMID- 15572393
TI  - Intravenous immunoglobulin does not increase FcgammaRIIB expression on
      monocytes/macrophages during acute Kawasaki disease.
AB  - OBJECTIVES: Intravenous immunoglobulin (IVIG) therapy has been reported to be
      effective for reducing the incidence of coronary artery lesions in Kawasaki
      disease (KD), an acute febrile vasculitis of unknown aetiology. Regarding the
      mechanism of IVIG in immune thrombocytopenic purpura (ITP), it has been reported
      that IVIG increases the expression of the inhibitory Fc receptor, FcgammaRIIB
      (CD32B), on splenic macrophages in a murine ITP model. Regarding the mechanism of
      IVIG during acute KD, we investigated whether or not IVIG increases the
      expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages.
      METHODS: The expression of FcgammaRIIB in peripheral blood CD14+
      monocytes/macrophages was determined before and after IVIG therapy in 13 patients
      with acute KD by flow cytometry. RESULTS: The percentage of CD14+ CD32B+
      monocytes/macrophages among peripheral blood mononuclear cells, the absolute
      number of CD14+ CD32B+ monocytes/macrophages and the percentage of CD14+ CD32B+
      monocytes/macrophages among CD14+ monocytes/macrophages in patients with acute KD
      before IVIG therapy were significantly increased compared with those after IVIG
      therapy and in controls. CD14+ CD32B+ monocytes/macrophages decreased to within
      the normal range soon after IVIG therapy. CONCLUSIONS: IVIG therapy in patients
      with KD did not increase the expression of FcgammaRIIB in peripheral blood CD14+
      monocytes/macrophages during the acute stage.

PMID- 15572394
TI  - Expression of DARC, CXCR3 and CCR5 in giant cell arteritis.
AB  - OBJECTIVES: Leucocyte infiltration is the hallmark of vasculitis, chemokines
      being mainly responsible for leucocyte migration into inflamed tissues. The
      objective was to evaluate the local expression of chemokines and chemokine
      receptors in biopsies of patients with giant cell arteritis (GCA) compared with
      arteries from patients with polymyalgia rheumatica (PMR). We studied the
      expression of CCR5, CXCR3 and that of the Duffy antigen/receptor of chemokine
      (DARC), a chemokine internalizing receptor (interceptor), in parallel to the
      expression of the CCR5 ligand RANTES/CCL5. METHODS: Paraffin-embedded tissue
      sections from six patients with GCA and five patients with PMR were available for
      immunohistological analysis of chemokine receptor expression. RANTES/CCL5 mRNA
      was detected in tissue sections by in situ hybridization. RESULTS: In patients
      with biopsy-proven giant cell arteritis, CCR5 and CXCR3 were highly expressed by
      infiltrating leucocytes in involved tissue sections. Predominant clustering of
      CCR5+ and CXCR3+ leucocytes was found in the adventitia and was co-localized with
      the expression of CCL5/RANTES mRNA. Interestingly, we found marked expression of
      DARC on adventitial high endothelial venules in vasculitis lesions of patients
      with GCA, while in arteries from patients with PMR DARC was only expressed on a
      low number of vessels with flat lining endothelium. CONCLUSIONS: The co
      localization of infiltrating CCR5+ and CXCR3+ leucocytes together with
      CCL5/RANTES and DARC in vasculitis lesions suggests a role for these chemokine
      receptors in leucocyte infiltration, possibly supported by DARC-mediated vascular
      presentation of chemokines.

PMID- 15572395
TI  - The patient's perspective and rheumatoid arthritis disease activity indexes.
AB  - BACKGROUND: Monitoring disease activity in rheumatoid arthritis (RA) patients by
      composite indexes is regarded as obligatory when following the recent
      recommendations for therapy. Whether these recommendations and the patient's
      perspective are in congruence is a crucial question with respect to the patient's
      compliance. The aim of the study was to obtain information on the patient's
      perspective with respect to the disease activity indexes used most often.
      METHODS: Two hundred and seven RA patients (157 female, 50 male; mean age 59.03
      yr, 17-86 yr) were enrolled in this cross-sectional evaluation. The patients'
      satisfaction [PATSAT (Austrian school mark system) 1 = excellent to 5 =
      unsatisfactory] and the patients' attitude to therapy (PATATT 1 = reduction, 2 =
      no change, 3 = increase) were assessed and related to the 28-joint Disease
      Activity Score (DAS28), the Simplified Disease Activity Index (SDAI) and the
      Modified Health Assessment Questionnaire (M-HAQ). Statistical evaluation was
      carried out by applying the Mann-Whitney U test, calculating chi2 and ANOVA.
      RESULTS: According to the DAS28 and the M-HAQ, patients were at a moderately
      active disease stage and had low functional deficiency. PATSAT was significantly
      correlated to the disease activity indexes (all PS < or = 0.002). The mean DAS28
      (2.56) at PATSAT 1 was within the remission range, whereas at PATSAT 5 a mean of
      5.52 indicated highly active disease. PATATT was found to be related to PATSAT,
      but did not completely parallel it. Reduction of therapy was intended at a mean
      DAS28 of 2.87, whereas a request for an increase did not occur before a mean
      DAS28 of 4.92. CONCLUSION: The patients' therapeutic attitudes are somewhat in
      line with their satisfaction, which mirrors disease activity to a great extent,
      though not with the common therapeutic recommendations. The DAS28 proved to be
      superior to both other indexes taking account of the patient's perspective. These
      results may provide guidance in patient care and education as well as therapeutic
      strategies.

PMID- 15572396
TI  - Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A
      prospective open-label study.
AB  - OBJECTIVE: To study the efficacy of alendronate, in the treatment of avascular
      necrosis (AVN) of the hip. METHODS: Sixty patients with AVN of the hip (100 hips
      with AVN) were studied. The follow-up period ranged from 3 months to 5 yr. The
      most common cause of AVN was steroids. Parameters studied were walking time,
      standing time, pain and disability on a visual analogue scale (VAS), range of
      motion of the hip, X-ray and MRI of the hip. All patients were treated with
      alendronate 10 mg/day (or 70 mg/week) along with 500-1000 mg of daily calcium and
      vitamin D supplements, and were advised to avoid weight-bearing. NSAIDs and
      analgesics were permitted as needed and were recorded. RESULTS: Forty-one
      patients (71 AVN hips) with AVN have been followed up for a minimum of 1 yr, 24
      patients (42 AVN hips) for 2 yr and 21 patients (37 AVN hips) for more than 2 yr
      (average 37 month). Fourteen patients have been followed up for less than 1 yr (3
      9 months). Significant reduction in pain and disability scores (P < 0.001) and
      significant increase in standing and walking time (P < 0.001) were observed. All
      hip movements improved at 1 yr (P value 0.000-0.009) with an insignificant
      decline after that (P > 0.001). Radiologically, the hips either stabilized in the
      same grade or progressed by one grade. MRI showed a decrease in marrow oedema in
      most cases at the 1-yr follow-up. Six patients (10 hips) required surgery and
      there were two (three hips) dropouts. The drug was well tolerated and there was a
      reduction in NSAID requirement. CONCLUSION: Alendronate reduces pain, improves
      function and retards AVN progression. Early surgical intervention can be avoided
      in most patients.

PMID- 15572397
TI  - A cytogenetic follow-up of some highly irradiated victims of the Chernobyl
      accident.
AB  - A follow-up of 10 highly irradiated men, mostly reactor crew, from the Chernobyl
      accident is described. Their pre-accident medical conditions and relevant medical
      status approximately 10-13 y later are listed. A comparison is made between
      estimates of their average whole-body penetrating radiation doses derived from
      several biological parameters. First estimates were based on their presenting
      severity of prodromal sickness, early changes in blood cell counts and dicentric
      chromosome aberrations in lymphocytes. In three cases ESR measurements on tooth
      enamel were also made. Retrospective dosimetry using FISH translocations was
      attempted 10-13 y later. This showed good agreement for those patients with the
      lower earlier dose estimates, up to about 3 Gy. For the others, extending up to
      about 12 Gy, the translocations indicated lower values, suggesting that in these
      cases translocations had somewhat declined. Repeated chromosomal examinations
      during the follow-up period showed an expected decline in dicentric frequencies.
      The pattern of decline was bi-phasic with a more rapid first phase, with a half
      life of approximately 4 months followed by a slower decline with half-lives
      around 2-4 y. The rapid phase persisted for a longer time in those patients who
      had received the highest doses. 10-13 y later dicentric levels were still above
      normal background, but well below the translocation frequencies.

PMID- 15572398
TI  - Natural radioactivity in some building materials in Cuba and their contribution
      to the indoor gamma dose rate.
AB  - The natural radioactivity of some building materials commonly used in Cuba was
      measured by gamma spectrometry. Typical concentrations encountered so far
      encountered are in the ranges: 47-2511 Bq kg(-1) for (40)K; 9-71 Bq kg(-1) for
      (226)Ra; and 2-38 Bq kg(-1) for (232)Th. The external gamma ray absorbed doses in
      indoor air and the corresponding effective dose-equivalents in a typical dwelling
      are presented in this paper.

PMID- 15572400
TI  - Local diagnostic reference levels in standard X-ray examinations.
AB  - The national diagnostic reference levels (NDRLs) form an efficient, concise and
      powerful standard for optimising radiation protection of a patient. However, in a
      large hospital, where many radiological departments are present, it is also
      possible to calculate and define lower dose values as local diagnostic reference
      levels (LDRLs). In our hospital there are eight radiological departments; in each
      of these, the entrance skin dose (ESD) distributions were determined for 10
      standard projections (AP Abdomen, PA and LAT Chest, AP and LAT Lumbar Spine, LAT
      Lumbo-Sacral Joint, AP Pelvis, PA and LAT Skull and AP Urinary tract) and then
      the ESDs were compared with data previously published and with Italian NDRLs. All
      ESD values were below the corresponding NDRLs. The maximum/minimum ratio of ESDs
      ranged from 3.9 (LAT Skull) to 34.3 (AP Abdomen) for individual adult patients
      and from 2.1 (PA Skull) to 6.5 (Urinary tract) across the mean values of the
      radiological departments. Finally, it is shown how LDRLs can be proposed to
      obtain a more fully optimised radiation protection of patients.

PMID- 15572401
TI  - Influence of radioactive aerosol and biological parameters of inhaled radon
      progeny on human lung dose.
AB  - The present work focuses on assessing the influence of biological and aerosol
      parameters on human lung dose. The dose conversion factor (DCF), which gives the
      relationship between the effective dose and the potential alpha energy
      concentration of inhaled short-lived radon progeny (218Po, 214Pb, 214Bi/214Po) is
      estimated using a dosimetric approach related to the International Commission on
      Radiological Protection(ICRP). The calculations are based on the measurements of
      the distribution of activity size of indoor radon progeny, their unattached
      fraction (f(b)) and potential alpha energy concentration (E). These experimental
      data are measured using a low-pressure cascade impactor and a wire-screen
      diffusion battery. Because of the short half-lives of the investigated nuclides,
      modifications that simplify the dose calculation are possible. The radioactive
      aerosol and biological parameters are varied in order to assess the DCF arising
      from the uncertainty of these parameters. The main emphasis is on the variation
      of the ventilation rate, breathing mode, critical cells for the induction of lung
      cancer and the parameters of the attached and unattached activity size
      distribution of the radon progeny. The investigation shows that the DCF is more
      than a factor of two higher than the values recommended by the ICRP, namely 3.9
      mSv WLM(-1) for the public and 5.1 mSv WLM(-1) for working places. The dose
      results for indoor aerosol conditions are in the range 2.3-2.6 mSv WLM(-1)
      depending on the breathing mode.

PMID- 15572402
TI  - Analysis of a Kalman filter based method for on-line estimation of atmospheric
      dispersion parameters using radiation monitoring data.
AB  - A Kalman filter method is discussed for on-line estimation of radioactive release
      and atmospheric dispersion from a time series of off-site radiation monitoring
      data. The method is based on a state space approach, where a stochastic system
      equation describes the dynamics of the plume model parameters, and the
      observables are linked to the state variables through a static measurement
      equation. The method is analysed for three simple state space models using
      experimental data obtained at a nuclear research reactor. Compared to direct
      measurements of the atmospheric dispersion, the Kalman filter estimates are found
      to agree well with the measured parameters, provided that the radiation
      measurements are spread out in the cross-wind direction. For less optimal
      detector placement it proves difficult to distinguish variations in the source
      term and plume height; yet the Kalman filter yields consistent parameter
      estimates with large associated uncertainties. Improved source term assessment
      results, when independent estimates of the plume height can be used. Perspectives
      for using the method in the context of nuclear emergency management are
      discussed, and possible extensions to the present modelling scheme are outlined,
      to account for realistic accident scenarios.

PMID- 15572403
TI  - Uncertainties evaluation for electrets based devices used in radon detection.
AB  - In recent years uncertainty evaluation in measurements has achieved great
      importance. National and international standards offer guidelines to evaluate
      uncertainties, but these procedures are, until now, not well understood by the
      operators. This is because of the fact that a detailed uncertainty evaluation is
      not an easy operation and a standard rule to apply in all cases is not available.
      Every measurement procedure has its own uncertainty evaluation. In this work,
      attention is focused upon the electret ion chambers (EIC), widely used in radon
      concentration measurements. Measurements of gamma radiation sensitivity are
      performed in a secondary standard calibration laboratory and measurement of radon
      concentration sensitivity is performed in a radon chamber 0.8 m3 in volume. Raw
      data are analysed to evaluate the calibration factors and the combined
      uncertainties are determined. The aim of the work is to give a practical method
      to assess the uncertainty of a radon measurement.

PMID- 15572404
TI  - Distinct functions of condensin I and II in mitotic chromosome assembly.
AB  - Condensin is a protein complex associated with mitotic chromosomes that has been
      implicated in chromosome condensation. In vertebrates, two types of condensin
      complexes have recently been identified, called condensin I and II. Here, we show
      that in mammalian cells condensin II associates with chromatin in prophase, in
      contrast to condensin I which is cytoplasmic and can thus interact with
      chromosomes only after nuclear envelope breakdown. RNA interference experiments
      in conjunction with imaging of live and fixed cells revealed that condensin II is
      required for chromosome condensation in early prophase, whereas condensin I
      appears to be dispensable at this stage. By contrast, condensin I is required for
      the complete dissociation of cohesin from chromosome arms, for chromosome
      shortening and for normal timing of progression through prometaphase and
      metaphase, whereas normal condensin II levels are dispensable for these
      processes. After depletion of both condensin complexes, the onset of chromosome
      condensation is delayed until the end of prophase, but is then initiated rapidly
      before nuclear envelope breakdown. These results reveal that condensin II and I
      associate with chromosomes sequentially and have distinct functions in mitotic
      chromosome assembly.

PMID- 15572406
TI  - In vivo analysis of 3-phosphoinositide dynamics during Dictyostelium phagocytosis
      and chemotaxis.
AB  - Phagocytosis and chemotaxis are receptor-mediated processes that require
      extensive rearrangements of the actin cytoskeleton, and are controlled by lipid
      second messengers such as phosphatidylinositol 3,4,5-trisphosphate
      [PtdIns(3,4,5)P3] and phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2]. We
      used a panel of pleckstrin homology (PH) domains with distinct binding
      specificities for PtdIns(3,4,5)P3 and PtdIns(3,4)P2 to study the spatiotemporal
      dynamics of these phosphoinositides in vivo. During phagocytosis and
      macropinocytosis PtdIns(3,4,5)P3 levels transiently increased at sites of
      engulfment, followed by a rapid PtdIns(3,4)P2 production round the
      phagosome/macropinosome upon its internalisation, suggesting that PtdIns(3,4,5)P3
      is degraded to PtdIns(3,4)P2. PTEN null mutants, which are defective in
      phagocytosis, showed normal rates of PtdIns(3,4,5)P3 degradation, but
      unexpectedly an accelerated PtdIns(3,4)P2 degradation. During chemotaxis to cAMP
      only PtdIns(3,4,5)P3 was formed in the plasma membrane, and no PtdIns(3,4)P2 was
      detectable, showing that all PtdIns(3,4,5)P3 was degraded by PTEN to
      PtdIns(4,5)P2. Furthermore, we showed that different PtdIns(3,4,5)P3 binding PH
      domains gave distinct spatial and temporal readouts of the same underlying
      PtdIns(3,4,5)P3 signal, enabling distinct biological responses to one signal.

PMID- 15572405
TI  - Role of myosin VIIa and Rab27a in the motility and localization of RPE
      melanosomes.
AB  - Myosin VIIa functions in the outer retina, and loss of this function causes human
      blindness in Usher syndrome type 1B (USH1B). In mice with mutant Myo7a,
      melanosomes in the retinal pigmented epithelium (RPE) are distributed abnormally.
      In this investigation we detected many proteins in RPE cells that could
      potentially participate in melanosome transport, but of those tested, only myosin
      VIIa and Rab27a were found to be required for normal distribution. Two other
      expressed proteins, melanophilin and myosin Va, both of which are required for
      normal melanosome distribution in melanocytes, were not required in RPE, despite
      the association of myosin Va with the RPE melanosome fraction. Both myosin VIIa
      and myosin Va were immunodetected broadly in sections of the RPE, overlapping
      with a region of apical filamentous actin. Some 70-80% of the myosin VIIa in RPE
      cells was detected on melanosome membranes by both subcellular fractionation of
      RPE cells and quantitative immunoelectron microscopy, consistent with a role for
      myosin VIIa in melanosome motility. Time-lapse microscopy of melanosomes in
      primary cultures of mouse RPE cells demonstrated that the melanosomes move in a
      saltatory manner, interrupting slow movements with short bursts of rapid movement
      (>1 RR01183m/second). In RPE cells from Myo7a-null mice, both the slow and rapid
      movements still occurred, except that more melanosomes underwent rapid movements,
      and each movement extended approximately five times longer (and further). Hence,
      our studies demonstrate the presence of many potential effectors of melanosome
      motility and localization in the RPE, with a specific requirement for Rab27a and
      myosin VIIa, which function by transporting and constraining melanosomes within a
      region of filamentous actin. The presence of two distinct melanosome velocities
      in both control and Myo7a-null RPE cells suggests the involvement of at least two
      motors other than myosin VIIa in melanosome motility, most probably, a
      microtubule motor and myosin Va.

PMID- 15572407
TI  - Compartmentalisation of the sperm plasma membrane: a FRAP, FLIP and SPFI analysis
      of putative diffusion barriers on the sperm head.
AB  - Spermatozoa are highly polarised cells with a compartmentalised distribution of
      lipids and proteins in their plasma membrane. It is not known how these
      compartments are stably maintained in what is essentially a fluid environment. In
      this investigation we have examined the hypothesis that intramembranous diffusion
      barriers selectively retain some components within compartments, while allowing
      free passage of others. A fluorescence loss in photobleaching analysis of the
      behaviour of the lipid reporter probe 1,1'-dihexadecyl-3,3,3'3'
      tetramethyindocarbocyanine (DiIC16) on the head of boar spermatozoa revealed that
      it was freely diffusing between all three compartments (anterior acrosome,
      equatorial segment and postacrosome). Spermatozoa also contained rapidly
      diffusing particles of DiIC16 over the anterior acrosome and equatorial segment.
      These particles, approximately 200 nm in diameter, were tracked in real time and
      their trajectories analysed by mean square displacement. Particle diffusion was
      essentially random over the anterior acrosome and equatorial segment but showed a
      periodicity in jump sizes and diffusion coefficients suggestive of
      microheterogeneities. Particles did not exchange between the equatorial segment
      and postacrosome, indicating a barrier at the junction between these two
      compartments. No barrier was detected between the equatorial segment and anterior
      acrosome. A model is proposed in which a molecular 'filter' is present at the
      equatorial segment-postacrosomal boundary that allows free passage of single
      molecules but not molecular complexes. Passage of heterogeneous complexes, such
      as lipid rafts, requires disassembly and reassembly on either side of the filter.

PMID- 15572408
TI  - Sem1, the yeast ortholog of a human BRCA2-binding protein, is a component of the
      proteasome regulatory particle that enhances proteasome stability.
AB  - Degradation of polyubiquitinated proteins by the proteasome often requires
      accessory factors; these include receptor proteins that bind both polyubiquitin
      chains and the regulatory particle of the proteasome. Overproduction of one such
      factor, Dsk2, is lethal in Saccharomyces cerevisiae and we show here that this
      lethality can be suppressed by mutations in SEM1, a gene previously recognized as
      an ortholog of the human gene encoding DSS1, which binds the BRCA2 DNA repair
      protein. Yeast sem1 mutants accumulate polyubiquitinated proteins, are defective
      for proteasome-mediated degradation and cannot grow under various stress
      conditions. Moreover, sem1 is synthetically lethal with mutations in proteasome
      subunits. We show that Sem1 is a component of the regulatory particle of the
      proteasome, specifically the lid subcomplex. Loss of Sem1 impairs the stability
      of the 26S proteasome and sem1Delta defects are greatly enhanced by simultaneous
      deletion of RPN10. The Rpn10 proteasome subunit appears to function with Sem1 in
      maintaining the association of the lid and base subcomplexes of the regulatory
      particle. Our data suggest a potential mechanism for this protein-protein
      stabilization and also suggest that an intact proteasomal regulatory particle is
      required for responses to DNA damage.

PMID- 15572409
TI  - Myocyte differentiation generates nuclear invaginations traversed by myofibrils
      associating with sarcomeric protein mRNAs.
AB  - Certain types of cell both in vivo and in vitro contain invaginated or convoluted
      nuclei. However, the mechanisms and functional significance of the deformation of
      the nuclear shape remain enigmatic. Recent studies have suggested that three
      types of cytoskeleton, microfilaments, microtubules and intermediate filaments,
      are involved in the formation of nuclear invaginations, depending upon cell type
      or conditions. Here, we show that undifferentiated mouse C2C12 skeletal muscle
      myoblasts had smoothsurfaced spherical or ellipsoidal nuclei, whereas prominent
      nuclear grooves and invaginations were formed in multinucleated myotubes during
      terminal differentiation. Conversion of mouse fibroblasts to myocytes by the
      transfection of MyoD also resulted in the formation of nuclear invaginations
      after differentiation. C2C12 cells prevented from differentiation did not have
      nuclear invaginations, but biochemically differentiated cells without cell fusion
      exhibited nuclear invaginations. Thus, biochemical differentiation is sufficient
      for the nuclear deformation. Although vimentin markedly decreased both in the
      biochemically and in the terminally differentiated cells, exogenous expression of
      vimentin in myotubes did not rescue nuclei from the deformation. On the other
      hand, non-striated premyofibrils consisting of sarcomeric actinmyosin filament
      bundles and cross-striated myofibrils traversed the grooves and invaginations.
      Time-lapse microscopy showed that the preformed myofibrillar structures cut
      horizontally into the nuclei. Prevention of myofibril formation retarded the
      generation of nuclear invaginations. These results indicate that the myofibrillar
      structures are, at least in part, responsible for the formation of nuclear
      grooves and invaginations in these myocytes. mRNA of sarcomeric proteins
      including myosin heavy chain and alpha-actin were frequently associated with the
      myofibrillar structures running along the nuclear grooves and invaginations.
      Consequently, the grooves and invaginations might function in efficient
      sarcomeric protein mRNA transport from the nucleus along the traversing
      myofibrillar structures for active myofibril formation.

PMID- 15572410
TI  - p38alpha, but not p38beta, inhibits the phosphorylation and presence of c-FLIPS
      in DISC to potentiate Fas-mediated caspase-8 activation and type I apoptotic
      signaling.
AB  - Pharmacological inhibitors of JNK (SP600125) and p38 (PD169316) sensitize tumor
      cells to Fas-mediated apoptosis. PD169316 is less potent than SP600125 and
      diminishes its effect when present together. Because the p38 isoforms that
      promote (p38alpha) or inhibit (p38beta) apoptosis are both suppressed by
      PD169316, we investigated their regulatory involvement in Fas-signaling. We
      report here, that p38alpha, but not p38beta, exerts its proapoptotic effect by
      inhibiting the phosphorylation and presence of c-FLIPS, but not c-FLIPL, in the
      DISC to promote caspase-8 activation and type I signaling in Fas-activated Jurkat
      cells. Its effect was enhanced by enforced expression of Flag-tagged p38alpha and
      was attenuated by its inactive mutant (p38alpha-AGF) or by translational
      silencing. By contrast, type II signaling was facilitated by p38alpha-dependent
      mitochondrial presence of tBid and inhibition of Bcl-2 (Ser70) phosphorylation as
      well as by p38alpha/beta-dependent mitochondrial localization of Bax and
      inhibition of phosphorylation of Bad (Ser112/Ser155). Potentiation of Fas
      mediated apoptosis by the inhibition of JNK1/2 correlated with the loss of Bad
      (Ser136) phosphorylation and was dependent on the stimulatory effect of p38alpha
      on DISC and the downstream effects of both p38alpha and p38beta. These data
      underscore the need to reassess the findings obtained with pan-p38 inhibitors and
      suggest that activation of p38alpha coupled with targeted inhibition of p38beta
      and JNK1/2 should optimally sensitize tumor cells to Fas-mediated apoptosis.

PMID- 15572411
TI  - Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts.
AB  - We previously demonstrated that hepatoblasts can be isolated from mouse fetal
      liver based on the expression of delta-like [corrected] (Dlk), also known as Pref
      1. Each Dlk+ hepatoblast forms a colony containing both albumin+ hepatocytes and
      cytokeratin 19+ (CK19) cholangiocytic cells on either type IV collagen or
      laminin. Here we show that extracellular matrices (ECMs) significantly affect the
      growth of Dlk+ cells. Dlk+ cells vigorously proliferated on type IV collagen
      coated dishes in the presence of EGF and HGF during the first 5 days, but their
      proliferative capability declined thereafter. Dlk+ cells also proliferated on
      laminin-coated plates and some colonies continued to expand even beyond one month
      after plating. These hepatic progenitor cells proliferating on laminin (HPPL)
      efficiently proliferated even after replating. Moreover, they were induced to
      differentiate into hepatocytes and cholangiocytes by overlaying Engelbreth-Holm
      Swarm sarcoma (EHS) gel and by embedding in type I collagen gel, respectively.
      HPPL acquired the metabolic functions of accumulating polysaccharides and
      detoxifying ammonium ions after hepatic differentiation. Surprisingly, HPPL
      expressed pancreatic genes such as Pdx1 when dexamethasone was depleted from the
      culture medium. Therefore, the long-term culture of hepatoblasts on laminin
      produces multi-potential hepatic progenitors, which possess a strong
      proliferative capability, differentiate into both hepatocytes and cholangiocytes,
      and potentially give rise to pancreatic cells.

PMID- 15572412
TI  - Importin beta is transported to spindle poles during mitosis and regulates Ran
      dependent spindle assembly factors in mammalian cells.
AB  - Spatial control is a key issue in cell division. The Ran GTPase regulates several
      fundamental processes for cell life, largely acting through importin molecules.
      The best understood of these is protein import through the nuclear envelope in
      interphase, but roles in mitotic spindle assembly are also established. In
      mammalian cells, in which centrosomes are major spindle organizers, a link is
      emerging between the Ran network, centrosomes and spindle poles. Here, we show
      that, after nuclear envelope breakdown, importin beta is transported to the
      spindle poles in mammalian cells. This localization is temporally regulated from
      prometaphase until anaphase, when importin beta dissociates from poles and is
      recruited back around reforming nuclei. Importin beta sediments with mitotic
      microtubules in vitro and its accumulation at poles requires microtubule
      integrity and dynamics in vivo. Furthermore, RNA interference-dependent
      inactivation of TPX2, the major Ran-dependent spindle organizer, abolishes
      importin beta accumulation at poles. Importin beta has a functional role in
      spindle pole organization, because overexpression yields mitotic spindles with
      abnormal, fragmented poles. Coexpression of TPX2 with importin beta mitigates
      these abnormalities. Together, these results indicate that the balance between
      importins and spindle regulators of the TPX2 type is crucial for spindle
      formation. Targeting of TPX2/importin-beta complexes to poles is a key aspect in
      Ran-dependent control of the mitotic apparatus in mammalian cells.

PMID- 15572413
TI  - Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via
      GTPase activity.
AB  - The mammalian homologues of yeast and Drosophila Fzo, mitofusin (Mfn) 1 and 2,
      are both essential for mitochondrial fusion and maintenance of mitochondrial
      morphology. Though the GTPase domain is required for Mfn protein function, the
      molecular mechanisms of the GTPase-dependent reaction as well as the functional
      division of the two Mfn proteins are unknown. To examine the function of Mfn
      proteins, tethering of mitochondrial membranes was measured in vitro by
      fluorescence microscopy using green fluorescence protein- or red fluorescent
      protein-tagged and Mfn1-expressing mitochondria, or by immunoprecipitation using
      mitochondria harboring HA- or FLAG-tagged Mfn proteins. These experiments
      revealed that Mfn1-harboring mitochondria were efficiently tethered in a GTP
      dependent manner, whereas Mfn2-harboring mitochondria were tethered with only low
      efficiency. Sucrose density gradient centrifugation followed by co
      immunoprecipitation revealed that Mfn1 produced oligomerized approximately 250
      kDa and approximately 450 kDa complexes in a GTP-dependent manner. The
      approximately 450 kDa complex contained oligomerized Mfn1 from distinct apposing
      membranes (docking complex), whereas the approximately 250 kDa complex was
      composed of Mfn1 present on the same membrane or in the membrane-solubilized
      state (cis complex). These results were also confirmed using blue-native PAGE.
      Mfn1 exhibited higher activity for this reaction than Mfn2. Purified recombinant
      Mfn1 exhibited approximately eightfold higher GTPase activity than Mfn2. These
      findings indicate that the two Mfn proteins have distinct activities, and suggest
      that Mfn1 is mainly responsible for GTP-dependent membrane tethering.

PMID- 15572414
TI  - Experimentally induced androgen depletion accentuates ethnicity-related contrasts
      in luteinizing hormone secretion in asian and caucasian men.
AB  - The basis for ethnicity-related distinctions in gonadotropin secretion are
      unknown but may have important populational and physiological implications. In
      male contraceptive trials, exogenous testosterone and progestins suppress
      spermatogenesis to a greater degree in Asian than Caucasian men. In addition, iv
      infusion of testosterone inhibits LH release more in Asian than Caucasian
      volunteers. We test the converse postulate that experimental reduction of
      androgen-dependent negative feedback by way of the steroidogenic inhibitor
      combination ketoconazole/dexamethasone will unveil ethnicity-related mechanisms
      of regulated LH secretion in young men. LH release was monitored by sampling
      blood every 10 min for 24 h followed by immunoradiometric assay, model-free pulse
      detection, an entropy (regulatory) statistic, and cosine regression. Statistical
      comparisons revealed that healthy young Asian and Caucasian men maintain
      comparable baseline concentrations of LH, testosterone, estradiol, SHBG, and
      molar testosterone to SHBG ratios. In contrast, the two ethnic groups differ
      prominently in each of basal, pulsatile, entropic, and 24-h rhythmic LH
      adaptations to short-term androgen withdrawal. Therefore, we postulate that
      physiological nonuniformity of sex steroid-dependent negative feedback in
      particular may contribute to populational diversity in LH regulation.

PMID- 15572415
TI  - Exogenous testosterone (T) alone or with finasteride increases physical
      performance, grip strength, and lean body mass in older men with low serum T.
AB  - Testosterone (T) therapy in older men with low serum T levels increases lean body
      mass and decreases fat mass. These changes might improve physical performance and
      strength; however, it has not been established whether T therapy improves
      functional outcome in older men. Moreover, concerns exist about the impact of T
      therapy on the prostate in older men. The administration of finasteride (F),
      which partially blocks the conversion of T to the more potent androgen,
      dihydrotestosterone, attenuates the impact of T replacement on prostate size and
      prostate-specific antigen. We hypothesized that T replacement in older,
      hypogonadal men would improve physical function and that the addition of F to
      this regimen would continue to provide the T-induced improvements in physical
      performance, strength, and body composition. Seventy men with low serum T (<350
      ng/dl), age 65 yr and older, were randomly assigned to receive one of three
      regimens for 36 months: 1) T enanthate, 200 mg im every 2 wk, with placebo pills
      daily (T-only); 2) T enanthate, 200 mg every 2 wk, with 5 mg F daily (T + F); or
      3) placebo injections and pills (placebo). We obtained serial measurements of
      timed physical performance, grip strength, lower extremity strength, body
      composition (by dual-energy x-ray absorptiometry), fasting cholesterol profiles,
      and hormones. Fifty men completed the 36-month protocol. After 36 months, T
      therapy significantly improved performance in a timed functional test when
      compared with baseline and placebo [4.3 +/- 1.6% (mean +/- sem, T-only) and 3.8
      +/- 1.0% (T + F) vs. -5.6 +/- 1.9% for placebo (P < 0.002 for both T and T + F
      vs. placebo)] and increased handgrip strength compared with baseline and placebo
      (P < 0.05). T therapy increased lean body mass [3.77 +/- 0.55 kg (T-only) and
      3.64 +/- 0.56 kg (T + F) vs. -0.21 +/- 0.55 kg for placebo (P < 0.0001)],
      decreased fat mass, and significantly decreased total cholesterol, low-density
      lipoprotein, and leptin, without affecting high-density lipoprotein, adiponectin,
      or fasting insulin levels. These results demonstrate that T therapy in older men
      with low serum T improves physical performance and strength over 36 months, when
      administered alone or when combined with F, and suggest that high serum levels of
      dihydrotestosterone are not essential for these beneficial effects of T in men.

PMID- 15572416
TI  - Comparison of hormone levels in nipple aspirate fluid of pre- and postmenopausal
      women: effect of oral contraceptives and hormone replacement.
AB  - The effects of ovarian suppression by oral contraceptives as well as hormone
      replacement therapy were studied on hormone levels and on products of hormone
      action in nipple aspirate fluid (NAF) from breasts of pre- and postmenopausal
      women. Multiple samples per subject revealed high consistency (intraclass
      correlation coefficients) for all products measured. Compared with premenopausal
      women, NAF progesterone was much lower in postmenopausal women, but NAF
      androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate
      concentrations were not different. With oral contraceptive use, estradiol,
      estrone sulfate, and progesterone levels were similarly lower in serum and NAF.
      In postmenopausal women, NAF estradiol and estrone sulfate were not significantly
      less than those in premenopausal women, nor were epidermal growth factor or
      cathepsin D levels, but IL-6 was elevated. Despite corresponding changes in
      hormones in serum and NAF over time, correlations based on simultaneous sampling
      were not significant. It is concluded that: 1) potential precursors of estradiol
      remain at comparable levels in the breast after menopause; 2) local synthesis is
      important for maintenance of estradiol levels in NAF of postmenopausal women but
      less important for progesterone; and 3) changes in the serum parameters are
      accurately reflected in NAF, but only after a matter of days. These findings
      provide additional validation for the physiological relevance of NAF hormone
      levels as potential breast cancer risk markers.

PMID- 15572417
TI  - The effect of perchlorate, thiocyanate, and nitrate on thyroid function in
      workers exposed to perchlorate long-term.
AB  - Perchlorate (ClO(4)(-)) and thiocyanate (SCN(-)) are potent and nitrate (NO(3)(
      )) a weak competitive inhibitor of the thyroid sodium-iodide symporter. To
      determine the effects of long-term, high ClO(4)(-) exposure on thyroid function,
      we conducted a study of 29 workers employed for at least 1.7 yr (50% over 5.9 yr)
      in an ammonium ClO(4)(-) production plant in Utah. Serum ClO(4)(-), SCN(-), and
      NO(3)(-); serum T(4), free T(4) index, total T(3), thyroglobulin (Tg), and TSH;
      14-h thyroid radioactive iodine uptake (RAIU); and urine iodine (I) and ClO(4)(-)
      were assessed after 3 d off (Pre) and during the last of three 12-h night shifts
      in the plant (During) and in 12 volunteers (C) not working in the plant. Serum
      and urine ClO(4)(-) were not detected in C; urine ClO(4)(-) was not detected in
      12 of 29 and was 272 microg/liter in 17 Pre workers; serum ClO(4)(-) was not
      detected in 27 of 29 Pre; and serum and urine ClO(4)(-) were markedly elevated
      during ClO(4)(-) exposure to 868 microg/liter and 43 mg/g creatinine,
      respectively. Serum SCN(-) and NO(3)(-) concentrations were similar in all
      groups. Thyroid RAIUs were markedly decreased in During compared with Pre (13.5
      vs. 21.5%; P < 0.01, paired t) and were associated with an increase in urine I
      excretion (230 vs. 148 microg I/g Cr; P = 0.02, paired t) but were similar to
      those in the C group (14.4%). Serum TSH and Tg concentrations were normal and
      similar in the three groups. Serum T(4) (8.3 vs. 7.7 microg/dl), free T(4) index
      (2.4 vs. 2.2), and total T(3) (147 vs. 134 ng/dl) were slightly but significantly
      increased in the During vs. Pre workers (P < 0.01, paired t). Thyroid volumes and
      patterns by ultrasound were similar in the 29 workers and 12 community
      volunteers. In conclusion, high ClO(4)(-) absorption during three nights work
      exposure decreased the 14-h thyroid RAIU by 38% in ClO(4)(-) production workers
      compared with the RAIU after 3 d off. However, serum TSH and Tg concentrations
      and thyroid volume by ultrasound were not affected by ClO(4)(-), suggesting that
      long-term, intermittent, high exposure to ClO(4)(-) does not induce
      hypothyroidism or goiter in adults.

PMID- 15572418
TI  - Functional characterization of calcium-sensing receptor codon 227 mutations
      presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal
      hyperparathyroidism.
AB  - Familial benign hypocalciuric hypercalcemia (FBHH), in which calcium homeostasis
      is disordered, can be distinguished from mild primary hyperparathyroidism by the
      finding of a heterozygous loss-of-function mutation in the calcium-sensing
      receptor (CaSR). Here, we report a Polish kindred with FBHH, the proband of which
      had undergone an unsuccessful parathyroidectomy. Direct sequence analysis of exon
      4 of her CASR gene identified a heterozygous R227Q mutation in the extracellular
      domain of the receptor. This mutation segregated with other affected family
      members. A de novo heterozygous R227L mutation had previously been identified in
      a case of neonatal hyperparathyroidism. We performed a functional analysis by
      transiently transfecting wild-type and mutant (R227Q, R227L) CaSRs in human
      embryonic kidney (HEK293) cells. Both mutant receptors were expressed at a
      similar level to that of the wild-type, demonstrated a 160-kDa molecular species
      consistent with having undergone full maturation, and were visualized on the cell
      surface. Although both mutants were impaired in their MAPK responses to
      increasing extracellular calcium concentrations relative to wild type, this was
      more marked for R227L (EC(50) = 9.7 mM) than R227Q (EC(50) = 7.9 mM) relative to
      wild type (EC(50) = 3.7 mM). When cotransfected with wild-type CaSR to mimic the
      heterozygous state, the curves for both R227Q and R227L were right shifted
      intermediate to the curves for wild type and the respective mutant. This
      differential responsiveness may account, in part, for the markedly different
      clinical presentation of the R227Q mutation, classic FBHH, vs. the neonatal
      hyperparathyroidism of the R227L mutation.

PMID- 15572419
TI  - Carrier frequency of congenital adrenal hyperplasia (21-hydroxylase deficiency)
      in a middle European population.
AB  - Based on newborn screening data, the carrier frequency of congenital adrenal
      hyperplasia (CAH) in the general population has been estimated to be 1:55. The
      higher CAH frequency (particularly of milder forms of the disease) reported for
      certain populations including Yugoslavs (1.6%) relates to population genetic and
      hormonal data. However, so far, true carrier frequency for CAH due to 21-OH
      deficiency has not been determined by comprehensive mutation analysis of the 21
      OH gene (CYP21A2) in an unselected European population. This study used CYP21A2
      genotyping (sequence/Southern blot analysis) to determine CAH carrier frequency
      in a middle European (Austrian) population. The study included 100 migrants from
      the former Yugoslavia and 100 individuals of non-Yugoslavian origin. None of
      these individuals showed clinical hyperandrogenism or had a family history of
      CAH. Genotyping 400 unrelated alleles from 200 clinically unaffected individuals,
      this study revealed a carrier frequency of 9.5%, including so-called "classic"
      (5.5%) and "nonclassic" (4%) CYP21A2-gene aberrations. The observed
      heterozygosity for CAH in Yugoslavs was not different (P = 0.8095) from that in
      non-Yugoslavs. In conclusion, the observed CAH carrier frequency of 9.5% suggests
      a higher prevalence of CAH heterozygosity in a middle European population than
      hitherto estimated independently of the individuals' Yugoslav or non-Yugoslav
      origin.

PMID- 15572420
TI  - Clinical utility of noncontrast computed tomography attenuation value (hounsfield
      units) to differentiate adrenal adenomas/hyperplasias from nonadenomas: Cleveland
      Clinic experience.
AB  - Radiological characterization of an adrenal tumor as adenoma may decrease the
      need for follow-up imaging studies, biopsies, and unnecessary adrenalectomies. We
      retrospectively reviewed 299 adrenalectomies in 290 patients at Cleveland Clinic
      Foundation over a recent 5-yr period to assess the value of noncontrast
      Hounsfield units (HU) in characterizing whether an adrenal mass is adenoma or
      nonadenoma. The mean (+/- SD) HU value for the adrenocortical adenoma/hyperplasia
      group was 16.2 +/- 13.6 and significantly lower (P < 0.0001) than primary
      adrenocortical cancers (36.9 +/- 4.1), metastases (39.2 +/- 15.2), and
      pheochromocytomas (38.6 +/- 8.2). The sensitivity and specificity for 10- and 20
      HU cutoff values to differentiate adenomas/hyperplasias from nonadenomas were
      40.5 and 100% and 58.2 and 96.9%, respectively. The size of the adrenal tumor had
      less value with only 40.7 and 81.3% sensitivity and 94.7 and 61.4% specificity
      for 2- and 4-cm cutoff values. A combination of less than or equal to 4-cm
      adrenal mass size and noncontrast computed tomography HU less than or equal to 20
      had 42.1% sensitivity and 100% specificity. Our study, the largest with surgical
      histopathology as the gold standard for diagnosis, supports a noncontrast
      computed tomography attenuation value of 10 HU as a safe cutoff value to
      differentiate adrenal adenomas/hyperplasias from nonadenomas.

PMID- 15572421
TI  - Progesterone receptor modulator CDB-2914 down-regulates proliferative cell
      nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and
      poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human
      uterine leiomyoma cells.
AB  - The present study was conducted to evaluate the effects of the progesterone
      receptor modulator CDB-2914 on proliferative activity and apoptosis in cultured
      human uterine leiomyoma cells. Isolated leiomyoma cells were subcultured in
      phenol red-free DMEM supplemented with 10% fetal bovine serum for 120 h and then
      stepped down to serum-free conditions for 12, 24, 48, and 96 h in the absence or
      presence of graded concentrations of CDB-2914 (10(-9), 10(-8), 10(-7), and 10(-6)
      M). The number of viable cultured leiomyoma cells was determined by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazodium bromide assay. Proliferating cell
      nuclear antigen (PCNA) expression was evaluated by immunocytochemistry and
      Western blot analysis. Apoptosis was examined by terminal deoxynucleotidyl
      transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL)
      assay. Caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and Bcl-2
      expression were assessed by Western blot analysis. Compared with untreated
      control cultures, treatment with CDB-2914 decreased the number of viable cultured
      leiomyoma cells and the PCNA-positive rate in those cells and increased the TUNEL
      positive rate in cultured leiomyoma cells in a dose-dependent manner. Western
      blot analysis revealed that treatment with CDB-2914 significantly decreased the
      expression of PCNA and Bcl-2 protein and increased the expression of cleaved
      caspase-3 and cleaved PARP in a dose-dependent manner compared with untreated
      control cultures. These results suggest that CDB-2914 inhibits the proliferation
      of cultured leiomyoma cells by down-regulating PCNA expression and induces
      apoptosis by up-regulating cleaved caspase-3 and PARP expression and down
      regulating Bcl-2 protein expression in those cells.

PMID- 15572422
TI  - High frequency of bone/bone marrow involvement in advanced medullary thyroid
      cancer.
AB  - High hematological toxicity has been observed with anti-carcinoembryonic antigen
      radioimmunotherapy (RIT) in medullary thyroid carcinoma (MTC), suggesting
      metastatic bone involvement (BI). This retrospective study evaluated the rate of
      BI in MTC patients enrolled in two phase-I/II RIT trials using anti
      carcinoembryonic antigen x anti-diethylenetriamine pentaacetic acid bispecific
      antibodies and [(131)I]di-diethylenetriamine pentaacetic acid hapten. Thirty-five
      patients underwent bone scintigraphy, bone magnetic resonance imaging (MRI), and
      post-RIT immunoscintigraphy (IS). IS performed in MTC patients was compared with
      IS conducted in 12 metastatic colorectal carcinoma (CRC) patients. Quantitative
      analysis of bone uptake was performed in three MTC and three CRC patients. In the
      MTC group, bone scintigraphy detected BI in 56.6% of patients, MRI in 75.8%, and
      IS in 88.6%. BI was confirmed by undirected (random) bone marrow biopsy, by bone
      surgery, or by two positive imaging methods in 74.3% of the patients. Sensitivity
      per patient of bone scintigraphy, MRI, and IS were 72.7, 100, and 100%,
      respectively. In contrast, IS visualized BI in only 33.3% of CRC patients; bone
      uptake was lower in CRC than in MTC patients. Bone MRI combined with post-RIT IS
      disclosed a much higher BI rate in advanced MTC than previously reported in the
      literature.

PMID- 15572423
TI  - Human bladder as a novel target for vitamin D receptor ligands.
AB  - Human prostate is now considered a target for vitamin D receptor (VDR) ligands,
      such as BXL-628. Because BXL-628 inhibited prostate growth without interfering
      with androgen signaling, it represents a new option for benign prostate
      hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate
      size, but also to compensatory bladder hypertrophy and eventual overactivity. We
      now report that human bladder expresses VDR (determined by real-time PCR
      immunohistochemistry and Western blot) and responds to VDR agonists, such as the
      natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative,
      BXL-628. Experiments were conducted with stromal cells derived from human bladder
      neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte
      growth factor (KGF) and androgen-induced cell proliferation and stimulated
      apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2.
      Prolonged serum starvation time-dependently pushed bladder stromal cells to
      express activated myofibroblast markers, such as desmin and smoothelin, without
      changing other contractile-related proteins and intermediate filaments, such as
      vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype
      modification. Because hypertrophy and starvation-induced bladder remodeling are
      supposed to underlie bladder overactivity, it is possible that BXL-628 might be
      helpful in reducing not only cumbersome symptoms related to prostate overgrowth,
      but also those related to bladder irritation.

PMID- 15572424
TI  - Molecular portrait of the progestagenic and estrogenic actions of tibolone:
      behavior of cellular networks in response to tibolone.
AB  - Tibolone is a synthetic steroid with estrogenic effects on brain, vagina, and
      bone without stimulating the endometrium. During tibolone treatment, it is
      thought that the progestagenic properties of tibolone stimulate cell
      differentiation, which effectively counterbalances the growth-stimulating effects
      of the estrogenic properties of tibolone. The objective of this study was to
      characterize the expression profile that reflects the endometrial responses to
      the separated estrogenic (growth-inducing) and progestagenic (growth-inhibiting)
      actions of tibolone, thus gaining insight into the counteracting effect of these
      properties of tibolone on the endometrium. The estrogenic action of tibolone was
      studied in the estrogen-responsive ECC1 cell line (expressing estrogen receptor
      alpha), and the progestagenic action was studied in the progesterone-responsive
      cell line Ishikawa PRAB-36 (expressing PRA and PRB). The data showed that the
      progestagenic and estrogenic effects of tibolone produce different expression
      profiles with a narrow overlap in genes; however, both properties modulate the
      same biological processes. The final genetic network analysis indicated that the
      estrogenic effect of tibolone is potentially counterbalanced by the progestagenic
      metabolite of tibolone via differential regulation of similar cellular processes.
      For example, both progestagenic and estrogenic properties stimulate
      proliferation, but they exert the opposite effect on apoptosis. The apoptosis
      network was stimulated by the progestagenic properties of tibolone; in contrast,
      the estrogenic effect of tibolone suppressed the apoptosis network. The current
      results indicate that this differential regulation is realized through modulation
      of a different group of genes and rarely via contraregulation of the same set of
      genes.

PMID- 15572425
TI  - Long-term persistence of the urine calcium-lowering effect of potassium
      bicarbonate in postmenopausal women.
AB  - Potassium bicarbonate (KBC) potently reduces urine calcium excretion in adult
      humans, including patients with hypertension or calcium urolithiasis, and
      postmenopausal women. In the latter, who have substantial risk of calcium
      deficiency, it remains unknown whether the observed short-term urine calcium
      lowering effect of KBC persists over years. We studied 170 postmenopausal women
      randomized to KBC 30, 60, or 90 mmol/d (KBC treatment), or placebo, for up to 36
      months. Each received a multivitamin with 400 IU vitamin D, and calcium carbonate
      as needed to produce a total dietary calcium intake of at least 30 mmol daily.
      Daily urine calcium excretion (UCaV) did not differ among groups at baseline (all
      groups mean +/- SD, 155 +/- 83 mg/d). From 1-36 months of KBC treatment,
      adjusting UCaV for creatinine (Cr) excretion, each dose of KBC reduced UCaV (P <
      0.01) with a dose-dependent trend (P = 0.05). The reduced UCaV/Cr persisted
      throughout the KBC treatment period (up to 36 months) in all KBC, and the
      greatest reductions occurred in the subjects with greatest baseline UCaV/Cr
      (Delta UCaV/Cr vs. baseline UCaV/Cr; P < 0.001). Twenty-eight percent of the
      subjects had high baseline calciuria (UCaV/Cr > 200 mg Ca/1000 mg Cr). With
      baseline UCaV/Cr of 250 mg/1000 mg Cr, KBC 60 mmol decreased UCaV/Cr by 55.8
      mg/1000 mg Cr, a potential daily calcium retention that over a 36-month period
      would accumulate up to 55,845 mg of calcium, nearly 5% of bone calcium content.
      KBC treatment induced a dose-dependent decrease in UCaV/Cr that persisted up to
      36 months, with the greatest decreases occurring in those women with the greatest
      baseline UCaV, nearly a third of whom had high baseline calciuria. Thus, one can
      preselect postmenopausal women most likely to have the urine calcium-lowering
      effect of KBC and predict their potential bone calcium increase.

PMID- 15572426
TI  - Amenorrhea in female athletes is associated with endothelial dysfunction and
      unfavorable lipid profile.
AB  - The aim of this study was to evaluate endothelial function measured as flow
      mediated dilatation (FMD) of the brachial artery and blood markers of
      cardiovascular disease in young female endurance athletes with menstrual
      disturbance. Age- and body mass index-matched groups of young endurance athletes
      with amenorrhea (n = 14), oligomenorrhea (n = 9), and regular cycles (n = 12) and
      sedentary controls (n = 12) were compared with respect to endothelial function,
      lipid profile, markers of inflammation, and endocrine status. We found a
      significantly decreased FMD in the amenorrheic athletes, compared with all other
      groups. Amenorrheic athletes also had the most unfavorable lipid profile with
      significantly higher total cholesterol and low-density lipoprotein, compared with
      the other athlete groups. The oligomenorrheic athletes had the lowest levels of
      total cholesterol, low-density lipoprotein, and apolipoprotein B of all groups
      and significantly lower in comparison with the amenorrheic group. However, with
      respect to FMD, the oligomenorrheic group represented an intermediate between
      amenorrheic and regularly cycling subjects. There was a gradual impairment of FMD
      and the lipid profile to the degree of menstrual disturbance supporting an
      association with estrogen status. We conclude that amenorrhea in young endurance
      athletes is associated with endothelial dysfunction and unfavorable lipid
      profile. Additional studies are needed to elucidate the clinical implications of
      these results with regard to long-term risk for cardiovascular disease.

PMID- 15572427
TI  - Renal contribution to increased clearance of exogenous growth hormone in obese
      hypertensive patients.
AB  - To evaluate the possible role of the kidney in the enhanced metabolic clearance
      rate (MCR) of GH in obesity, we studied the kinetics of GH and renal fractional
      extraction of GH (RFEGH) in 12 male hypertensive patients over a wide range of
      body weights (71.7-129 kg) while undergoing contrast angiography on suspicion of
      renal artery stenosis. A continuous infusion of recombinant human GH was
      administered during a continuous infusion of somatostatin to suppress endogenous
      GH secretion. After 2 h of GH infusion, when plasma GH had reached a steady state
      at concentrations that were still in the physiological range, blood was sampled
      from the left and right renal arteries and veins for determination of GH levels.
      Subsequently, the GH infusion was stopped, and GH kinetics were investigated with
      noncompartmental analysis. In none of the patients was hemodynamically
      significant renal artery stenosis present. Whole body MCR of GH averaged 375 +/-
      142 ml/min. Average GH levels were significantly higher in arterial plasma than
      in simultaneously sampled renal venous plasma (P < 0.001). RFEGH was 8.6 +/-
      6.8%. The MCRs of both GH and RFEGH correlated significantly with body weight,
      body fat mass, and endogenous creatinine clearance. Renal uptake of GH per 100 g
      kidney tissue correlated inversely with MCR. These results suggest that RFEGH
      rises with increasing adiposity, but per unit of renal mass, the capacity of the
      kidney to remove GH from the circulation falls at high MCR values.

PMID- 15572428
TI  - Truncal adiposity, relative growth hormone deficiency, and cardiovascular risk.
AB  - We hypothesized that endogenous GH would be reduced in healthy women with
      relative truncal adiposity despite lack of generalized obesity and that decreased
      GH would be associated with increased cardiovascular risk markers. Fifteen
      healthy female volunteers were divided into two groups, low truncal fat and high
      truncal fat, of comparable body mass index (BMI). Age and BMI (23.7 +/- 2.1 vs.
      25.8 +/- 2.8 kg/m(2)) were similar in the two groups. Trunk fat was higher in the
      high-truncal-fat group, as designed. Twenty-four-hour mean GH, amplitude, and
      basal GH concentration were 41, 32, and 36% lower, respectively, in the high
      truncal-fat group, but GH pulse frequency and IGF-I levels did not differ. In a
      stepwise regression model, trunk fat accounted for 38% of the variation of mean
      GH levels (P = 0.02), but neither total body fat nor BMI were significant
      determinants of mean GH in the model. There was a strong inverse association
      between mean 24-h GH and both truncal fat and cardiovascular risk markers,
      including high-sensitivity C-reactive protein. Our data suggest that visceral
      adiposity may be associated with reduced endogenous GH in healthy women, even in
      the absence of generalized obesity, and that decreased GH secretion may be
      associated with increased cardiovascular risk markers in this population.

PMID- 15572429
TI  - Recombinant cell ultrasensitive bioassay for measurement of estrogens in
      postmenopausal women.
AB  - A recent analysis of data from nine studies provided convincing evidence that
      plasma estradiol measurements predict the risk of breast cancer in normal
      postmenopausal women. However, the median values detected by the various assays
      used in this study varied by 5-fold. These and other published data in normal
      postmenopausal women suggest that assays measuring low plasma estradiol
      concentrations suffer from problems of sensitivity, specificity, and precision.
      Availability of a practical, low-cost, specific, precise, and ultrasensitive
      estrogen assay might allow enhanced prediction of the risk of breast cancer and
      provide an objective means of selecting postmenopausal women for breast cancer
      prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was
      recently validated for use in prepubertal children. We postulated that the RCUB
      might also prove useful for measurement of postmenopausal levels and designed the
      present study to examine this possibility. Thirty normal postmenopausal
      volunteers provided blood samples for measurement of estrogen by RCUB and, for
      comparison, by RIA. The estrogenic activity measured by RCUB [mean +/- sd, 11.9
      +/- 10.9 pmol/liter (SI units, 3.23 +/- 2.96 pg/ml] was significantly lower than
      estradiol levels measured by RIA [43.7 +/- 44.0 pmol/liter (11.9 +/- 12.0 pg/ml)]
      in our volunteer subjects (P < 0.00001). Nonetheless, plasma estradiol levels
      measured by bioassay were significantly correlated with the estrogenic activity
      measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r
      = 0.85). To obtain biological evidence of the validity of the RCUB, we related
      plasma estrogen levels to body weight and body mass index and found highly
      significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28
      of 30 postmenopausal women were found to have estrogen levels in the prepubertal
      range with the RCUB. The levels detected by RCUB were similar to those previously
      reported using an ultrasensitive but less practical yeast bioassay. These results
      provide validation for the RCUB in postmenopausal women and suggest that it might
      prove useful for selection of women for drug therapy to prevent breast cancer.

PMID- 15572430
TI  - Association of the intestinal fatty acid-binding protein Ala54Thr polymorphism
      and abdominal adipose tissue in African-American and Caucasian women.
AB  - Genetic variants in the intestinal fatty acid-binding protein-2 (FABP2) gene have
      been associated with body composition phenotypes. We examined the association
      between the Ala(54)Thr variant in the FABP2 gene and levels of visceral (VAT) and
      sc (SAAT) abdominal fat in a group of 223 premenopausal African-American (n =
      103) and Caucasian (n = 120) women. Subjects were genotyped for the marker. In
      addition, body composition was assessed by dual energy x-ray absorptiometry, and
      VAT was determined from a single computed tomography scan. The frequency of the
      Thr mutant allele did not differ significantly by ethnic group. After adjusting
      for total body fat, total abdominal adipose tissue (TAT) and SAAT were
      significantly lower in carriers of either one or two copies of the mutant Thr
      allele (P < 0.01). There was no association between total fat mass or VAT and the
      FABP2 polymorphism. Separate analyses by ethnic group showed that the association
      between the polymorphism and TAT and SAAT was observed in Caucasian (P < 0.01),
      but not in African-American (not significant), women. We conclude that women
      carriers of the FABP2 Thr allele have lower TAT and SAAT than noncarriers of the
      mutation. This association is present in Caucasian, but not in African-American,
      women.

PMID- 15572431
TI  - Alcohol and endogenous sex steroid levels in postmenopausal women: a cross
      sectional study.
AB  - Breast cancer risk increases with increased levels of alcohol consumption,
      potentially through an effect on sex hormone levels. In a cross-sectional study
      among Dutch participants (n = 17,357) of the European Prospective Investigation
      into Cancer and Nutrition conducted in Utrecht, The Netherlands (Prospect-EPIC),
      we investigated the relation between alcohol intake and estrogen and androgen
      levels. Alcohol intake was calculated from a food frequency questionnaire. Women
      were included if they were postmenopausal, had donated a blood sample, and did
      not use hormone replacement therapy or oral contraceptives at the time of blood
      donation (n = 1093). Women who consumed more than 25 g of alcohol per day had
      higher levels of estrone (P(trend) = 0.001), estradiol (P(trend) = 0.03),
      dehydroepiandrosterone sulfate (P(trend) = 0.18), and higher estrone/estradiol
      (P(trend) = 0.14) and estrone/androstenedione (P(trend) = 0.06) ratios, compared
      with nondrinkers. Levels of androstenedione, testosterone, and SHBG did not
      differ between women who consumed alcohol and nondrinkers. Furthermore, there
      were no differences in the free androgen index or estradiol to testosterone
      ratio. In conclusion, levels of estrogens and dehydroepiandrosterone sulfate are
      higher in women who consume more alcohol. This finding supports the hypothesis
      that alcohol use may increase breast cancer risk at least partially through an
      effect on sex steroid levels.

PMID- 15572432
TI  - Cardiovascular fitness and exercise as determinants of insulin resistance in
      postpubertal adolescent females.
AB  - In obese adolescents, body mass index (BMI) is a poor predictor of insulin
      resistance, and the potential role of diminished physical activity has not been
      quantitated. We measured possible determinants of sensitivity to insulin in 53
      adolescent females with a BMI between the 10th and the 95th percentile. We
      hypothesized that across weight and fitness spectra, relative fat mass, rather
      than BMI, and cardiovascular fitness would be predictors of insulin resistance.
      We measured body composition by total-body dual x-ray absorptiometry. Self
      reported weekly frequency of aerobic exercise for 1 h (RDE) was recorded, and
      maximal oxygen consumption (VO(2)max) was measured. Insulin sensitivity was
      estimated by homeostasis model assessment index (HOMA(IR)) derived from fasting
      glucose and insulin concentrations. BMI was not related to HOMA(IR) (P = 0.20),
      RDE showed a marginal relationship (P = 0.049), whereas percent body fat and
      VO(2)max were significantly related to HOMA(IR) (P = 0.01 and 0.0008,
      respectively). In a multiple regression model, VO(2)max was a more critical
      determinant of insulin resistance than percent body fat (P = 0.03 vs. P = 0.67)
      or RDE (P = 0.01 vs. 0.51). For prevention strategies in youth, physical
      inactivity may represent a greater metabolic risk than obesity alone.

PMID- 15572433
TI  - Sonic hedgehog regulates CRH signal transduction in the adult pituitary.
AB  - Sonic hedgehog (Shh) is a signaling protein that binds to Patched and mediates
      its effects through Gli transcription factors. Shh is important in regulating
      survival and growth in both the embryo and the adult. It is known to be involved
      in pituitary development, but its role in the adult pituitary has not been
      investigated. Here, we show Shh and Gli1 immunoreactivity in adult human
      corticotroph cells. Administration of Shh (5 microg/ml) alone and in combination
      with corticotrophin-releasing hormone (CRH; 100 nM) in dispersed rat anterior
      pituitary and AtT-20 mouse corticotrophinoma cells increased corticotrophin
      (ACTH) secretion and pro-opiomelanocortin (POMC) promoter activity. Shh and CRH
      act additively in increasing CRH receptor 1 (CRH-R1). Unexpectedly, we found that
      CRH on its own increased Gli-dependent transcription, which in turn stimulated
      POMC transcription. Gli1 is necessary for CRH signaling, since knocking down Gli1
      by RNA interference abolished the stimulatory effect of CRH on POMC. Taken
      together, our results demonstrate a new role for Shh and Gli1 in corticotroph
      function and provide a new link between Shh and CRH signaling pathways.

PMID- 15572435
TI  - Swiss adolescents' and adults' perceptions of cannabis use: a qualitative study.
AB  - Few studies have attempted to investigate the nature of adolescents' and adults'
      conceptions and perceptions of cannabis use. Our objectives were to explore
      adolescent and adult perception of use and misuse of cannabis, and their opinions
      and beliefs about the current legal context and preventive strategies. We used
      focus group discussions with four categories of stakeholders: younger (12-15 year
      old) adolescents, older (16-19 year old) adolescents, parents of teenagers and
      professionals working with young people. In some areas (legal framework, role of
      the media, importance of early preventive interventions), we found consensual
      attitudes and beliefs across the four groups of participants. In all four groups,
      participants did not have any consensual vision of the risks of cannabis use or
      the definition of misuse. In the area of the prevention of cannabis use/misuse,
      while parents focused on the potential role of professionals and the media, thus
      minimizing their own educational and preventive role, professionals stressed the
      importance of parental control and education. Within the Swiss context, we
      conclude there exists an urgent need for information and clarification of the
      issues linked with cannabis use and misuse directed at parents and professionals.

PMID- 15572434
TI  - Ryanodine receptor-operated activation of TRP-like channels can trigger critical
      Ca2+ signaling events in pancreatic beta-cells.
AB  - There is little information available concerning the link between the ryanodine
      (RY) receptors and the downstream Ca(2+) signaling events in beta-cells. In fura
      2 loaded INS-1E cells, activation of RY receptors by 9-methyl 5,7
      dibromoeudistomin D (MBED) caused a rapid rise of [Ca(2+)]i followed by a plateau
      and repetitive [Ca(2+)]i spikes on the plateau. The [Ca(2+)]i plateau was
      abolished by omission of extracellular Ca(2+) and by SKF 96365. In the presence
      of SKF 96365, MBED produced a transient increase of [Ca(2+)]i, which was
      abolished by thapsigargin. Activation of RY receptors caused Ca(2+) entry even
      when the ER Ca(2+) pool was depleted by thapsigargin. The [Ca(2+)]i plateau was
      not inhibited by nimodipine or ruthenium red, but was inhibited by membrane
      depolarization, La(3+), Gd(3+), niflumic acid, and 2-aminoethoxydiphenyl borate,
      agents that inhibit the transient receptor potential channels. The [Ca(2+)]i
      spikes were inhibited by nimodipine and ryanodine, indicating that they were due
      to Ca(2+) influx through the voltage-gated Ca(2+) channels and Ca(2+)-induced
      Ca(2+) release (CICR). Activation of RY receptors depolarized membrane potential
      as measured by patch clamp. Thus, activation of RY receptors leads to coherent
      changes in Ca(2+) signaling, which includes activation of TRP-like channels,
      membrane depolarization, activation of the voltage-gated Ca(2+) channels and
      CICR.

PMID- 15572436
TI  - Compliance and support for smoke-free school policies.
AB  - Our objective was to examine factors associated with compliance and support for a
      smoke-free campus before and after a 1995 campus-wide smoking ban for everyone,
      including teachers and visitors, in California. Adolescent (12-17 years) data
      from the 1993, 1996, 1999 and 2002 (N approximately 6000 each year) California
      Tobacco Surveys (population-based telephone surveys) were analyzed. Trends in
      compliance with smoke-free school policies and support for smoke-free campuses
      were examined among students in public and private schools. Perceived compliance
      with the no-smoking rule by most or all student smokers increased from 43.7 +/-
      1.6% in 1993 to 71.5 +/- 1.4% in 2002. While non-smokers have overwhelmingly
      favored smoke-free school grounds since 1993 (more than 85% each survey year),
      support among current smokers increased from 55.8 +/- 4.7% in 1996 to 69.1 +/-
      6.8% in 2002. Student smokers who saw teachers smoking in school were less likely
      to favor school smoking bans (odds ratio = 0.25, 95% confidence interval 0.12
      0.49). The percentage of private school students seeing teachers smoke on school
      grounds has been at least twice that of public school students since 1996.
      Compliance with and support for smoke-free schools increased since smoking was
      banned on campus for everyone. Perceived compliance by teachers, much lower in
      private schools, appears to undermine student smokers' support of this policy.
      Increased efforts are necessary to communicate to teachers the importance of
      their modeling of policy compliance to students.

PMID- 15572437
TI  - Written and verbal information versus verbal information only for patients being
      discharged from acute hospital settings to home: systematic review.
AB  - This article presents the results of a Cochrane review which was conducted to
      determine the effectiveness of providing written and verbal health information
      compared with verbal information only to patients being discharged from acute
      hospital settings to home. Only two trials met the review inclusion criteria. In
      both trials the participants were parents of children being discharged from
      hospital to home. The two outcomes measured in both trials were knowledge and
      satisfaction. The review confirms that providing written and verbal health
      information is more effective in improving knowledge and satisfaction than
      providing verbal information only for parents of children being discharged from
      hospital to home. There is no evidence of the effectiveness of the intervention
      in adults who provide their own care after discharge from hospital. Further
      research is required which involves adult patients being discharged from hospital
      to home, and research which measures a range of outcomes which include
      readmission rates, recovery times, patient/carer knowledge, complication rates,
      service utilization and costs (community, outpatient and inpatient), confidence
      in one's own care management, stress and anxiety levels, satisfaction with
      services provided prior to discharge, and adherence to recommended care.

PMID- 15572438
TI  - The Chronic Illness Resources Survey: cross-validation and sensitivity to
      intervention.
AB  - There is great interest in, but few instruments to assess, multiple levels of
      support and community resources from a social-ecological perspective. This study
      evaluated the psychometric characteristics of the Chronic Illness Resources
      Survey (CIRS) and its sensitivity to a multifaceted social-ecological
      intervention to enhance personally relevant community resources supportive of
      healthful lifestyles. Participants were 293 post-menopausal women having type 2
      diabetes who were part of a multiple-behavior lifestyle change program. Key
      measures included the CIRS, a validated Food Frequency Questionnaire, the Kristal
      Fat and Fiber Behavior Questionnaire, the CHAMPS Activities Questionnaire for
      Older Adults, and other measures of social support. Results revealed that the
      CIRS displayed good psychometric characteristics in this new sample, was
      significantly correlated as predicted with established measures of social
      support, was sensitive to intervention, and partially mediated the effects of
      intervention on both dietary and physical activity outcomes. The 22-item CIRS
      scale appears useful for assessing multilevel support resources, predicting
      successful behavior change and detecting social-ecological intervention effects.

PMID- 15572439
TI  - Comparing demographic, health status and psychosocial strategies of audience
      segmentation to promote physical activity.
AB  - The goal of audience segmentation is to identify population subgroups that are
      homogeneous with respect to certain variables associated with a given outcome or
      behavior. When such groups are identified and understood, targeted intervention
      strategies can be developed to address their unique characteristics and needs.
      This study compares the results of audience segmentation for physical activity
      that is based on either demographic, health status or psychosocial variables
      alone, or a combination of all three types of variables. Participants were 1090
      African-American and White adults from two public health centers in St Louis, MO.
      Using a classification-tree algorithm to form homogeneous groups, analyses showed
      that more segments with greater variability in physical activity were created
      using psychosocial versus health status or demographic variables and that a
      combination of the three outperformed any individual set of variables. Simple
      segmentation strategies such as those relying on demographic variables alone
      provided little improvement over no segmentation at all. Audience segmentation
      appears to yield more homogeneous subgroups when psychosocial and health status
      factors are combined with demographic variables.

PMID- 15572440
TI  - Regulation of flagellar dynein activity by a central pair kinesin.
AB  - The motility of cilia and flagella is powered by dynein ATPases associated with
      outer doublet microtubules. However, a flagellar kinesin-like protein that may
      function as a motor associates with the central pair complex. We determined that
      Chlamydomonas reinhardtii central pair kinesin Klp1 is a phosphoprotein and, like
      conventional kinesins, binds to microtubules in vitro in the presence of
      adenosine 5'-[beta,gamma-imido]triphosphate, but not ATP. To characterize the
      function of Klp1, we generated RNA interference expression constructs that reduce
      in vivo flagellar Klp1 levels. Klp1 knockdown cells have flagella that either
      beat very slowly or are paralyzed. EM image averages show disruption of two
      structures associated with the C2 central pair microtubule, C2b and C2c. Greatest
      density is lost from part of projection C2c, which is in a position to interact
      with doublet-associated radial spokes. Klp1 therefore retains properties of a
      motor protein and is essential for normal flagellar motility. We hypothesize that
      Klp1 acts as a conformational switch to signal spoke-dependent control of dynein
      activity.

PMID- 15572441
TI  - Human Rhesus-associated glycoprotein mediates facilitated transport of NH(3) into
      red blood cells.
AB  - Rhesus (Rh) antigens are carried by a membrane complex that includes Rh proteins
      (D and CcEe), Rh-associated glycoproteins (RhAG), and accessory chains (LW and
      CD47) associated by noncovalent bonds. In heterologous expression systems, RhAG
      and its kidney orthologs function as ammonium transporters. In red blood cells
      (RBCs), it is generally accepted that NH(3) permeates by membrane lipid
      diffusion. We have revisited these issues by studying RBC and ghosts from human
      and mouse genetic variants with defects of proteins that comprise the Rh complex.
      In both normal and mutant cells, stopped-flow analyses of intracellular pH
      changes in the presence of inwardly directed methylammonium
      (CH(3)NH(+)(3)+CH(3)NH(2)) or ammonium (NH(+)(4)+NH(3)) gradients showed a rapid
      alkalinization phase. Cells from human and mouse variants exhibited a decrease in
      their kinetic rate constants that was strictly correlated to the degree of
      reduction of their RhAG/Rhag expression level. Rate constants were not affected
      by a reduction of Rh, CD47, or LW. CH(3)NH(2)/NH(3) transport was characterized
      by (i) a sensitivity to mercurials that is reversible by 2-mercaptoethanol and
      (ii) a reduction of alkalinization rate constants after bromelain digestion,
      which cleaves RhAG. The results show that RhAG facilitates CH(3)NH(2)/NH(3)
      movement across the RBC membrane and represents a potential example of a gas
      channel in mammalian cells. In RBCs, RhAG may transport NH(3) to detoxifying
      organs, like kidney and liver, and together with nonerythroid tissue orthologs
      may contribute to the regulation of the systemic acid-base balance.

PMID- 15572442
TI  - A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on
      Vancouver Island (British Columbia, Canada).
AB  - Cryptococcus gattii causes life-threatening infection of the pulmonary and
      central nervous systems in hosts with normal immunity and traditionally has been
      considered to be restricted geographically to tropical and subtropical climates.
      The recent outbreak of C. gattii in the temperate climate of Vancouver Island,
      BC, Canada, led to a collaborative investigation. The objectives of the current
      study were to ascertain the environmental source of the outbreak infections,
      survey the molecular types of the outbreak and environmental cryptococcal
      isolates, and determine the extent of genetic diversity among the isolates. PCR
      fingerprinting and amplified fragment length polymorphism (AFLP) were used to
      examine the genotypes, and mating assays were performed to determine the mating
      type of the isolates. All outbreak and environmental isolates belonged to C.
      gattii. Concordant results were obtained by using PCR-fingerprinting and AFLP
      analysis. The vast majority of clinical and veterinary infections were caused by
      isolates of the molecular type VGII/AFLP6, but two were caused by molecular type
      VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two
      or three subtypes were observed within VGII/AFLP6 among outbreak and
      environmental isolates. All mating-competent isolates were of the alpha-mating
      type. The emergence of this usually tropical pathogen on Vancouver Island
      highlights the changing distribution of this genotype and emphasizes the
      importance of an ongoing collaborative effort to monitor the global epidemiology
      of this yeast.

PMID- 15572443
TI  - Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional
      gel electrophoresis and mass spectrometry.
AB  - We have investigated the plasma proteome by using 2D gel electrophoresis and MS
      from patients with severe acute respiratory syndrome (SARS). A complete proteomic
      analysis was performed on four patients with SARS in different time courses, and
      a total of 38 differential spots were selected for protein identification. Most
      of the proteins identified are acute phase proteins, and their presence
      represents the consequence of serial cascades initiated by SARS-coronavirus
      infection. There are several proteins that have never been identified in plasma
      before using 2D gel electrophoresis, among which peroxiredoxin II was chosen for
      further study by analyzing additional 20 plasma samples from patients with
      probable and suspected SARS and patients with fever, respectively. The results
      showed that the level of plasma peroxiredoxin II in patients with SARS is
      significantly high and could be secreted by T cells. Taken together, our findings
      indicate that active innate immune responses, along with the oxidation-associated
      injuries, may play a major role in the pathogenesis of SARS.

PMID- 15572444
TI  - Water clusters in nonpolar cavities.
AB  - We explore the structure and thermodynamics of water clusters confined in
      nonpolar cavities. By calculating the grand-canonical partition function term by
      term, we show that small nonpolar cavities can be filled at equilibrium with
      highly structured water clusters. The structural and thermodynamic properties of
      these encapsulated water clusters are similar to those observed experimentally in
      the gas phase. Water filling is highly sensitive to the size of the cavity and
      the strength of the interactions with the cavity wall. Water penetration into
      pores can thus be modulated by small changes in the polarity and structure of the
      cavity. Implications on water penetration into proteins are discussed.

PMID- 15572445
TI  - Human cytomegalovirus immediate-early 1 protein facilitates viral replication by
      antagonizing histone deacetylation.
AB  - The human cytomegalovirus 72-kDa immediate-early (IE)1 and 86-kDa IE2 proteins
      are expressed at the start of infection, and they are believed to exert much of
      their function through promiscuous transcriptional activation of viral and
      cellular gene expression. Here, we show that the impaired growth of an IE1
      deficient mutant virus in human fibroblasts is efficiently rescued by histone
      deacetylase (HDAC) inhibitors of three distinct chemical classes. In the absence
      of IE1 expression, the viral major IE and UL44 early promoters exhibited
      decreased de novo acetylation of histone H4 during the early phase of infection,
      and the hypoacetylation correlated with reduced transcription and accumulation of
      the respective gene products. Consistent with these findings, IE1 interacts
      specifically with HDAC3 within infected cells. We also demonstrate an interaction
      between IE2 and HDAC3. We propose that the ability to modify chromatin is
      fundamental to transcriptional activation by IE1 and, likely, IE2 as well.

PMID- 15572446
TI  - Ordered patterns of liquid crystal toroidal defects by microchannel confinement.
AB  - In this article we present experimental results demonstrating an approach to
      controlling the size and spatial patterning of defect domains in a smectic liquid
      crystal (LC) by geometric confinement in surface-modified microchannels. By
      confining the LC 4'-octyl-4-cyanobiphenyl in mum-sized rectangular channels with
      controlled surface polarity, we were able to generate defect domains that are not
      only nearly uniform in size but also arranged in quasi-2D ordered patterns.
      Atomic force microscopy measurements revealed that the defects have a toroidal
      topology, which we argue is dictated by the boundary conditions imposed by the
      walls of the microchannel. We show that the defects can be considered to be
      colloidal objects, which interact with each other to form ordered patterns. This
      method opens the possibility for exploiting the unique optical and rheological
      properties associated with LC defects to making new materials. For example, the
      control of the shape, size, and spatial arrangement of the defects at the
      mesoscale suggests applications in patterning, templating, and when extended to
      lyotropic LCs, a process leading to uniform-sized spherical particles for
      chemical encapsulation and delivery.

PMID- 15572447
TI  - Fusion-protein truncation provides new insights into leukemogenesis.

PMID- 15572448
TI  - Critical roles of the guanylyl cyclase B receptor in endochondral ossification
      and development of female reproductive organs.
AB  - Guanylyl cyclase B is the receptor for a small peptide (C-type natriuretic
      peptide) produced locally in many different tissues. To unravel the functions of
      the receptor, we generated mice lacking guanylyl cyclase B through gene
      targeting. Expression of the receptor mRNA in tissues such as bone and female
      reproductive organs was evident, and significant phenotypes associated with each
      of these tissues were apparent in null mice. A dramatic impairment of
      endochondral ossification and an attenuation of longitudinal vertebra or limb
      bone growth were seen in null animals. C-type natriuretic peptide-dependent
      increases of guanylyl cyclase B activity, but not basal enzyme activity, appeared
      to be required for the progression of endochondral ossification. Female mice were
      infertile, but male mice were not. This result was due to the failure of the
      female reproductive tract to develop. Thus, the guanylyl cyclase B receptor is
      critical for the development of both bone and female reproductive organs.

PMID- 15572449
TI  - Microbial ecology comes of age and joins the general ecology community.

PMID- 15572450
TI  - Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.
AB  - Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition
      receptors of the innate immune system that bind and, in some cases, hydrolyze
      bacterial PGNs. We determined the crystal structure, at 2.30-A resolution, of the
      C-terminal PGN-binding domain of human PGRP-Ialpha in complex with a muramyl
      tripeptide representing the core of lysine-type PGNs from Gram-positive bacteria.
      The peptide stem of the ligand is buried at the deep end of a long binding
      groove, with N-acetylmuramic acid situated in the middle of the groove, whose
      shallow end can accommodate a linked N-acetylglucosamine. Although most
      interactions are with the peptide, the glycan moiety also seems to be essential
      for specific recognition by PGRPs. Conservation of key PGN-contacting residues
      shows that all PGRPs employ this basic PGN-binding mode. The structure pinpoints
      variable residues that likely mediate discrimination between lysine- and
      diaminopimelic acid-type PGNs. We also propose a mechanism for PGN hydrolysis by
      Zn(2+)-containing PGRPs.

PMID- 15572451
TI  - Three-dimensional structure and organization of a receptor/signaling complex.
AB  - Transmembrane signaling in bacterial chemotaxis has become an important model
      system for experimental and theoretical studies. These studies have provided a
      wealth of detailed molecular structures, including the structures of CheA, CheW,
      and the cytoplasmic domain of the serine receptor Tsr. How these three proteins
      interact to form the receptor/signaling complex remains unknown. By using EM and
      single-particle image analysis, we present a three-dimensional reconstruction of
      the receptor/signaling complex. The complex contains CheA, CheW, and the
      cytoplasmic portion of the aspartate receptor Tar. We observe density consistent
      with a structure containing 24 aspartate-receptor monomers and additional density
      sufficient to house the expected four CheA monomers and six CheW monomers. Within
      this bipolar structure are four groups of three receptor dimers that are not
      threefold symmetric and are therefore unlike the symmetric trimers observed in
      the x-ray crystal structure of the cytoplasmic domain of the serine receptor. In
      the latter, the interdimer contacts occur in the signaling domains near the
      hairpin loop. In our structure, the signaling domains within trimers appear
      spaced apart by the presence of CheA and CheW. This structure argues against
      models where one CheA and one CheW bind to the outer face of each of the dimers
      in the trimer. This structure of the receptor/signaling complex provides an
      additional basis for understanding the architecture of the large arrays of
      chemotaxis receptors, CheA, and CheW found at the cell poles in motile bacteria.

PMID- 15572452
TI  - Inorganic polyphosphate in Bacillus cereus: motility, biofilm formation, and
      sporulation.
AB  - Chains of inorganic polyphosphate (poly-P) with hundreds of P(i) residues linked
      by phosphoanhydride bonds, as in ATP, are found in every bacterial, fungal,
      plant, and animal cell, in which they perform various functions. In the spore
      forming Bacillus cereus, we have identified three principal enzymes and genes
      involved in the metabolism of poly-P, namely, (i) poly-P kinase (PPK), which
      synthesizes poly-P reversibly from ATP, (ii) exopolyphosphatase (PPX), which
      hydrolyzes poly-P to P(i), and (iii) poly-P/AMP phosphotransferase (PAP), which
      uses poly-P as a donor to convert AMP to ADP, reversibly. In the null mutant of
      ppk, poly-P levels are reduced to <5% of the WT; in the ppx mutant, the PPK
      activity is elevated 10-fold, and the accumulation of poly-P is elevated
      approximately 1,000-fold. All of the null mutants of ppk, ppx, and pap showed
      defects in motility and biofilm formation, but sporulation efficiency was
      impaired only in the ppx mutant. These enzymes and genes in B. cereus are nearly
      identical to those in the very closely related pathogen Bacillus anthracis, and,
      thus, they may provide attractive targets for the treatment of anthrax.

PMID- 15572453
TI  - Genetic networks with canalyzing Boolean rules are always stable.
AB  - We determine stability and attractor properties of random Boolean genetic network
      models with canalyzing rules for a variety of architectures. For all power law,
      exponential, and flat in-degree distributions, we find that the networks are
      dynamically stable. Furthermore, for architectures with few inputs per node, the
      dynamics of the networks is close to critical. In addition, the fraction of genes
      that are active decreases with the number of inputs per node. These results are
      based upon investigating ensembles of networks using analytical methods. Also,
      for different in-degree distributions, the numbers of fixed points and cycles are
      calculated, with results intuitively consistent with stability analysis; fewer
      inputs per node implies more cycles, and vice versa. There are hints that genetic
      networks acquire broader degree distributions with evolution, and hence our
      results indicate that for single cells, the dynamics should become more stable
      with evolution. However, such an effect is very likely compensated for by
      multicellular dynamics, because one expects less stability when interactions
      among cells are included. We verify this by simulations of a simple model for
      interactions among cells.

PMID- 15572454
TI  - Highly conserved upstream sequences for transcription factor genes and
      implications for the regulatory network.
AB  - Identifying evolutionarily conserved blocks in orthologous genomic sequences is
      an effective way to detect regulatory elements. In this study, with the aim of
      elucidating the architecture of the regulatory network, we systematically
      estimated the degree of conservation of the upstream sequences of 3,750 human
      mouse orthologue pairs along 8-kb stretches. We found that the genes with high
      upstream conservation are predominantly transcription factor (TF) genes. In
      particular, developmental process-related TF genes showed significantly higher
      conservation of the upstream sequences than other TF genes. Such extreme upstream
      conservation of the developmental process-related TF genes suggests that the
      regulatory networks involved with developmental processes have been
      evolutionarily well conserved in both human and mouse lineages.

PMID- 15572455
TI  - Regulation of behavioral maturation by a primer pheromone produced by adult
      worker honey bees.
AB  - Previous research showed that the presence of older workers causes a delayed
      onset of foraging in younger individuals in honey bee colonies, but a specific
      worker inhibitory factor had not yet been identified. Here, we report on the
      identification of a substance produced by adult forager honey bees, ethyl oleate,
      that acts as a chemical inhibitory factor to delay age at onset of foraging.
      Ethyl oleate is synthesized de novo and is present in highest concentrations in
      the bee's crop. These results suggest that worker behavioral maturation is
      modulated via trophallaxis, a form of food exchange that also serves as a
      prominent communication channel in insect societies. Our findings provide
      critical validation for a model of self-organization explaining how bees are able
      to respond to fragmentary information with actions that are appropriate to the
      state of the whole colony.

PMID- 15572456
TI  - Genomic data support the hominoid slowdown and an Early Oligocene estimate for
      the hominoid-cercopithecoid divergence.
AB  - Several lines of indirect evidence suggest that hominoids (apes and humans) and
      cercopithecoids (Old World monkeys) diverged around 23-25 Mya. Importantly,
      although this range of dates has been used as both an initial assumption and as a
      confirmation of results in many molecular-clock analyses, it has not been
      critically assessed on its own merits. In this article we test the robusticity of
      the 23- to 25-Mya estimate with approximately 150,000 base pairs of orthologous
      DNA sequence data from two cercopithecoids and two hominoids by using quartet
      analysis. This method is an improvement over other estimates of the hominoid
      cercopithecoid divergence because it incorporates two calibration points, one
      each within cercopithecoids and hominoids, and tests for a statistically
      appropriate model of molecular evolution. Most comparisons reject rate constancy
      in favor of a model incorporating two rates of evolution, supporting the
      "hominoid slowdown" hypothesis. By using this model of molecular evolution, the
      hominoid-cercopithecoid divergence is estimated to range from 29.2 to 34.5 Mya,
      significantly older than most previous analyses. Hominoid-cercopithecoid
      divergence dates of 23-25 Mya fall outside of the confidence intervals estimated,
      suggesting that as much as one-third of ape evolution has not been
      paleontologically sampled. Identifying stem cercopithecoids or hominoids from
      this period will be difficult because derived features that define crown
      catarrhines need not be present in early members of these lineages. More sites
      that sample primate habitats from the Oligocene of Africa are needed to better
      understand early ape and Old World monkey evolution.

PMID- 15572457
TI  - Familiar route loyalty implies visual pilotage in the homing pigeon.
AB  - Wide-ranging animals, such as birds, regularly traverse large areas of the
      landscape efficiently in the course of their local movement patterns, which
      raises fundamental questions about the cognitive mechanisms involved. By using
      precision global-positioning-system loggers, we show that homing pigeons (Columba
      livia) not only come to rely on highly stereotyped yet surprisingly inefficient
      routes within the local area but are attracted directly back to their
      individually preferred routes even when released from novel sites off-route. This
      precise route loyalty demonstrates a reliance on familiar landmarks throughout
      the flight, which was unexpected under current models of avian navigation. We
      discuss how visual landmarks may be encoded as waypoints within familiar route
      maps.

PMID- 15572458
TI  - Crossing the apnoeic threshold: causes and consequences.
AB  - This brief review addresses the characteristics, lability and the mechanisms
      underlying the hypocapnic-induced apnoeic threshold which is unmasked during NREM
      sleep. The role of carotid chemoreceptors as fast, sensitive detectors of dynamic
      changes in CO2 is emphasized and placed in historical context of the long-held
      debate over central vs. peripheral contributions to CO2 sensing and to apnoea.
      Finally, evidence is presented which points to a significant role for unstable,
      central respiratory motor output as a significant contributor to upper airway
      narrowing and obstruction during sleep.

PMID- 15572459
TI  - Stability and instability of regulation of intracellular calcium.
AB  - [Ca2+]i is used as a signal in many tissues. In this review we discuss the
      mechanisms that regulate [Ca2+]i and, importantly, what determines their
      stability. Brief mention is made of the effects of feedback gain and delays on
      stability. The control of cytoplasmic Ca concentration is shown to be generally
      stable as Ca pumping is essentially an instantaneous function of [Ca2+]i. In
      contrast, regulation of the Ca content of intracellular stores may be less
      stable. One example of this is instability in the control of sarcoplasmic
      reticulum (SR) Ca content in cardiac muscle. An increase of SR Ca content
      increases the systolic Ca transient amplitude. This in turn decreases Ca influx
      into the cell and increases efflux, thereby restoring SR Ca to control levels.
      This feedback system has an inherent delay and is potentially unstable if the
      gain is increased beyond a certain level. This instability produces Ca transients
      of alternating amplitude and may contribute to the clinical syndrome of pulsus
      alternans.

PMID- 15572460
TI  - Mitochondrial Ca2+ transport in frog early distal tubule.
AB  - A global and transient rise of intracellular Ca2+ (Ca2+i) is central to the
      operation of pump-leak coupling in the frog early distal tubule (EDT). The
      endoplasmic reticulum (ER) is the site of this Ca2+ release and reuptake;
      however, it is likely that other intracellular pools, such as mitochondria, also
      contribute to cellular Ca2+ homeostasis. The present study was performed to seek
      evidence of mitochondrial Ca2+ transport in the frog EDT. Experiments were
      performed on isolated and permeabilized EDT segments from the frog kidney loaded
      with the low-affinity, Ca2+-sensitive fluorescent indicator, mag-fura-2. Ca2+
      uptake in the absence of SarcoEndoplasmic Reticulum Calcium ATPase (SERCA)
      activity (inhibition by 2,5-di-t-butyl hydroquinone, TBQ) was evident at a bath
      [Ca2+] of 1 microm, but not at 200 nm, in the presence of ATP. This uptake was
      sensitive to the protonophore FCCP and the ATP-synthase inhibitor oligomycin.
      Ca2+ uptake was also stimulated by respiratory substrates; this uptake was
      enhanced by oligomycin and reversed by the application of FCCP. These findings
      provide the first evidence of mitochondrial Ca2+ transport in renal tubules,
      which appears to occur via a low-affinity pathway and which will act as a
      physiological Ca2+ buffer, protecting the cell from large increases in Ca2+i.

PMID- 15572461
TI  - Salivary secretion assay for drug efficacy for cystic fibrosis in mice.
AB  - Computerized assays on cultured cells ex vivo have been used to screen thousands
      of compounds for their effectiveness in correcting the basic physiological defect
      in cystic fibrosis (CF). While a number of these compounds appear promising,
      their effectiveness will almost certainly need to be demonstrated in animals
      before therapeutic tests in humans will be possible. We show herein that the
      function of salivary secretion in the mouse model for CF could be used as a
      simple, easy and rapid in vivo assay for drug effects. We demonstrate that
      salivary secretory capacity stimulated with a beta-adrenergic agonist closely
      reflects the genotype of origin. Specifically, the mean maximal secretory rate of
      saliva in normal wild type (+/+) mice was about 1.5 times higher than that of the
      mean rate in heterozygote (+/-) mice and more than 50 times greater than in CF (
      /-) mice. Total saliva secreted per stimulated period obeyed a similar phenotype
      genotype segregation. The data indicate that salivary secretory rates in CF mice
      could be used to assay potential drugs for their effectiveness in correcting the
      secretory defect in cystic fibrosis.

PMID- 15572462
TI  - Effects of supra-physiological changes in human ovarian hormone levels on maximum
      force production of the first dorsal interosseus muscle.
AB  - The purpose of this study was to investigate the effects of supra-physiological
      changes in ovarian hormone levels on maximum force production in two conditions,
      one physiological (pregnancy) and one pseudo-physiological (in vitro
      fertilization (IVF) treatment). Forty IVF patients were tested at four distinct
      stages of treatment and 35 women were tested during each trimester of pregnancy
      and following parturition. Maximum voluntary isometric force per unit cross
      sectional area of the first dorsal interosseus muscle was measured. Plasma
      concentrations of total and bioavailable oestradiol and testosterone were
      measured, in addition to the total concentrations of progesterone and human
      chorionic gonadotropin. Despite significant changes in the concentrations of
      total progesterone, 17beta-oestradiol, bioavailable oestradiol and testosterone
      between phases, strength did not change significantly throughout IVF treatment
      (1.30+/-0.29, 1.16+/-0.38, 1.20+/-0.29 and 1.26+/-0.34 N mm-2, respectively, in
      the 4 phases of IVF treatment). Force production was significantly higher during
      the second trimester of pregnancy than following childbirth (1.33+/-0.20 N mm-2
      at week 12 of pregnancy, 1.51+/-0.42 N mm-2 at week 20, 1.15+/-0.26 N mm-2 at
      week 36 and 0.94+/-0.31 N mm-2 at week 6 postnatal) but was not significantly
      correlated with any of the hormones measured. These data suggest that extreme
      changes in the concentrations of reproductive hormones do not affect the maximum
      force-generating capacity of young women.

PMID- 15572463
TI  - A graph based algorithm for generating EST consensus sequences.
AB  - MOTIVATION: EST sequences constitute an abundant, yet error prone resource for
      computational biology. Expressed sequences are important in gene discovery and
      identification, and they are also crucial for the discovery and classification of
      alternative splicing. An important challenge when processing EST sequences is the
      reconstruction of mRNA by assembling EST clusters into consensus sequences.
      RESULTS: In contrast to the more established assembly tools, we propose an
      algorithm that constructs a graph over sequence fragments of fixed size, and
      produces consensus sequences as traversals of this graph. We provide a tool
      implementing this algorithm, and perform an experiment where the consensus
      sequences produced by our implementation, as well as by currently available
      tools, are compared to mRNA. The results show that our proposed algorithm in a
      majority of the cases produces consensus of higher quality than the established
      sequence assemblers and at a competitive speed. AVAILABILITY: The source code for
      the implementation is available under a GPL license from
      http://www.ii.uib.no/~ketil/bioinformatics/ CONTACT: ketil@ii.uib.no.

PMID- 15572464
TI  - MACAT--microarray chromosome analysis tool.
AB  - By linking differential gene expression to the chromosomal localization of genes,
      one can investigate microarray data for characteristic patterns of expression
      phenomena involving sizeable parts of specific chromosomes. We have implemented a
      statistical approach for identifying significantly differentially expressed
      chromosome regions. We demonstrate the applicability of the approach on a
      publicly available data set on acute lymphocytic leukemia. AVAILABILITY: The R
      package MACAT can be obtained from
      http://www.compdiag.molgen.mpg.de/software/macat.shtml SUPPLEMENTARY INFORMATION:
      http://www.compdiag.molgen.mpg.de/software/macat.shtml.

PMID- 15572465
TI  - YODA: selecting signature oligonucleotides.
AB  - MOTIVATION: Selecting oligonucleotide probes for use in microarray design, and
      other applications requiring signature sequences, involves identifying sequences
      which will bind strongly to their intended target, while binding only weakly (or
      preferably, not at all) to non-target sequences which may be present in the
      hybridization reaction. While many tools to assist in selection of such sequences
      exist, all the ones we examined lack important oligo design and software
      features. RESULTS: YODA is an application for assisting biological researchers in
      selecting signature sequences. It incorporates a custom sequence similarity
      search to find potential cross-hybridizing non-target sequences. For this task,
      most oligo design tools rely on BLAST, which is ill suited for it due to an
      unacceptable risk of false negatives. YODA supports multiple probe design goals
      including single-genome, multiple-genome, pathogen-host and species/strain
      identification. A graphical interface is provided as well as a command-line
      interface, both of which support many user-controlled parameters. YODA is easy to
      install and use and runs on Windows, Mac OS X and Linux platforms. AVAILABILITY:
      Freely available (LGLP) along with source code and additional documentation at
      http://pathport.vbi.vt.edu/YODA CONTACT: enordber@vbi.vt.edu.

PMID- 15572466
TI  - SYMMETREE: whole-tree analysis of differential diversification rates.
AB  - SymmeTREE implements several tests of differential diversification rates that
      exploit information on the topological distribution of species diversity
      throughout entire trees to address two general questions: (1) Has a given tree
      experienced significant variation in diversification rates among its branches?
      and (2) If so, along which branches have significant shifts in diversification
      rate occurred? These explicitly model-based methods are robust to uncertainty in
      estimates of branch length/duration and can accommodate incompletely resolved
      trees and other forms of phylogenetic uncertainty. AVAILABILITY:
      http://www.phylodiversity.net/bmoore/software.html CONTACT: brian.moore@yale.edu.

PMID- 15572467
TI  - Correlation of amino acid preference and mammalian viral genome type.
AB  - MOTIVATION: In the event of an outbreak of a disease caused by an initially
      unknown pathogen, the ability to characterize anonymous sequences prior to
      isolation and culturing of the pathogen will be helpful. We show that it is
      possible to classify viral sequences by genome type (dsDNA, ssDNA, ssRNA positive
      strand, ssRNA negative strand, retroid) using amino acid distribution. RESULTS:
      In this paper we describe the results of analysis of amino acid preference in
      mammalian viruses. The study was carried out at the genome level as well as two
      shorter sequence levels: short (300 amino acids) and medium length (660 amino
      acids). The analysis indicates a correlation between the viral genome types
      dsDNA, ssDNA, ssRNA positive strand, ssRNA negative strand and retroid and amino
      acid preference. We investigated three different models of amino acid preference.
      The simplest amino acid preference model, 1-AAP, is a normalized description of
      the frequency of amino acids in genomes of a viral genome type. A slightly more
      complex model is the ordered pair amino acid preference model (2-AAP), which
      characterizes genomes of different viral genome types by the frequency of ordered
      pairs of amino acids. The most complex and accurate model is the ordered triple
      amino acid preference model (3-AAP), which is based on ordered triples of amino
      acids. The results demonstrate that mammalian viral genome types differ in their
      amino acid preference. AVAILABILITY: The tools used to format and analyze data
      and supplementary material are available at
      http://www.cse.sc.edu/~rose/aminoPreference/index.html CONTACT: rose@cse.sc.edu.

PMID- 15572468
TI  - Drosophila DNase I footprint database: a systematic genome annotation of
      transcription factor binding sites in the fruitfly, Drosophila melanogaster.
AB  - Despite increasing numbers of computational tools developed to predict cis
      regulatory sequences, the availability of high-quality datasets of transcription
      factor binding sites limits advances in the bioinformatics of gene regulation.
      Here we present such a dataset based on a systematic literature curation and
      genome annotation of DNase I footprints for the fruitfly, Drosophila
      melanogaster. Using the experimental results of 201 primary references, we
      annotated 1367 binding sites from 87 transcription factors and 101 target genes
      in the D.melanogaster genome sequence. These data will provide a rich resource
      for future bioinformatics analyses of transcriptional regulation in Drosophila
      such as constructing motif models, training cis-regulatory module detectors,
      benchmarking alignment tools and continued text mining of the extensive
      literature on transcriptional regulation in this important model organism.
      AVAILABILITY: http://www.flyreg.org/ CONTACT: cbergman@gen.cam.ac.uk.

PMID- 15572469
TI  - Synergy of human Pol II core promoter elements revealed by statistical sequence
      analysis.
AB  - MOTIVATION: The subject of our paper is bioinformatics analysis of the
      distinguishing features of human promoter DNA sequences, in particular of
      synergetic combinations of core promoter elements therein. We suppose that
      specific scenarios of transcription initiation are essentially related to various
      particular implementations of the interaction of basal transcription machinery
      with promoter DNA, depending on the presence and mutual positioning of core
      promoter elements. RESULTS: In addition to the combinations of core promoter
      elements previously experimentally confirmed [TATA box and Initiator (Inr),
      Downstream Promoter Element (DPE) and Inr, and TFIIB recognition element (BRE)
      and TATA box] we propose other alternate synergetic combinations: BRE and Inr,
      BRE and DPE, and TATA and DPE with respective models. The suggestion is based on
      a high statistical significance of the alternate combinations in promoters,
      comparable with the significance of the known combinations. We also present
      arguments that the BRE element is statistically more important than previously
      thought, and suggest possible mechanisms of action of the core elements in the
      promoters with multiple transcription start sites. CONTACT: ioschikhes
      1@medctr.osu.edu SUPPLEMENTARY INFORMATION: Supplementary information is
      available at http://bmi.osu.edu/~ilya/synergy/Gershenzon_SuppMat-R.pdf.

PMID- 15572470
TI  - Optimal number of features as a function of sample size for various
      classification rules.
AB  - MOTIVATION: Given the joint feature-label distribution, increasing the number of
      features always results in decreased classification error; however, this is not
      the case when a classifier is designed via a classification rule from sample
      data. Typically (but not always), for fixed sample size, the error of a designed
      classifier decreases and then increases as the number of features grows. The
      potential downside of using too many features is most critical for small samples,
      which are commonplace for gene-expression-based classifiers for phenotype
      discrimination. For fixed sample size and feature-label distribution, the issue
      is to find an optimal number of features. RESULTS: Since only in rare cases is
      there a known distribution of the error as a function of the number of features
      and sample size, this study employs simulation for various feature-label
      distributions and classification rules, and across a wide range of sample and
      feature-set sizes. To achieve the desired end, finding the optimal number of
      features as a function of sample size, it employs massively parallel computation.
      Seven classifiers are treated: 3-nearest-neighbor, Gaussian kernel, linear
      support vector machine, polynomial support vector machine, perceptron, regular
      histogram and linear discriminant analysis. Three Gaussian-based models are
      considered: linear, nonlinear and bimodal. In addition, real patient data from a
      large breast-cancer study is considered. To mitigate the combinatorial search for
      finding optimal feature sets, and to model the situation in which subsets of
      genes are co-regulated and correlation is internal to these subsets, we assume
      that the covariance matrix of the features is blocked, with each block
      corresponding to a group of correlated features. Altogether there are a large
      number of error surfaces for the many cases. These are provided in full on a
      companion website, which is meant to serve as resource for those working with
      small-sample classification. AVAILABILITY: For the companion website, please
      visit http://public.tgen.org/tamu/ofs/ CONTACT: e-dougherty@ee.tamu.edu.

PMID- 15572471
TI  - BIAS: Bioinformatics Integrated Application Software.
AB  - MOTIVATION: We introduce a development platform especially tailored to
      Bioinformatics research and software development. BIAS (Bioinformatics Integrated
      Application Software) provides the tools necessary for carrying out integrative
      Bioinformatics research requiring multiple datasets and analysis tools. It
      follows an object-relational strategy for providing persistent objects, allows
      third-party tools to be easily incorporated within the system and supports
      standards and data-exchange protocols common to Bioinformatics. AVAILABILITY:
      BIAS is an OpenSource project and is freely available to all interested users at
      http://www.mcb.mcgill.ca/~bias/. This website also contains a paper containing a
      more detailed description of BIAS and a sample implementation of a Bayesian
      network approach for the simultaneous prediction of gene regulation events and of
      mRNA expression from combinations of gene regulation events. CONTACT:
      hallett@mcb.mcgill.ca.

PMID- 15572472
TI  - Generalized Venn diagrams: a new method of visualizing complex genetic set
      relations.
AB  - MOTIVATION: Microarray experiments generate vast amounts of data. The unknown or
      only partially known functional context of differentially expressed genes may be
      assessed by querying the Gene Ontology database via GOMiner. Resulting tree
      representations are difficult to interpret and are not suited for visualization
      of this type of data. Methods are needed to effectively visualize these complex
      set relationships. RESULTS: We present a visualization approach for set
      relationships based on Venn diagrams. The proposed extension enhances the usual
      notion of Venn diagrams by incorporating set size information. The cardinality of
      the sets and intersection sets is represented by their corresponding circle
      (polygon) sizes. To avoid local minima, solutions to this problem are sought by
      evolutionary optimization. This generalized Venn diagram approach has been
      implemented as an interactive Java application (VennMaster) specifically designed
      for use with GOMiner in the context of the Gene Ontology database. AVAILABILITY:
      VennMaster is platform-independent (Java 1.4.2) and has been tested on Windows
      (XP, 2000), Mac OS X, and Linux. Supplementary information and the software (free
      for non-commercial use) are available at http://www.informatik.uni
      ulm.de/ni/mitarbeiter/HKestler/vennm together with a user documentation. CONTACT:
      hans.kestler@medizin.uni-ulm.de.

PMID- 15572473
TI  - Detecting interspecific recombination with a pruned probabilistic divergence
      measure.
AB  - MOTIVATION: A promising sliding-window method for the detection of interspecific
      recombination in DNA sequence alignments is based on the monitoring of changes in
      the posterior distribution of tree topologies with a probabilistic divergence
      measure. However, as the number of taxa in the alignment increases or the sliding
      window size decreases, the posterior distribution becomes increasingly diffuse.
      This diffusion blurs the probabilistic divergence signal and adversely affects
      the detection accuracy. The present study investigates how this shortcoming can
      be redeemed with a pruning method based on post-processing clustering, using the
      Robinson-Foulds distance as a metric in tree topology space. RESULTS: An
      application of the proposed scheme to three synthetic and two real-world DNA
      sequence alignments illustrates the amount of improvement that can be obtained
      with the pruning method. The study also includes a comparison with two
      established recombination detection methods: Recpars and the DSS (difference of
      sum of squares) method. AVAILABILITY: Software, data and further supplementary
      material are available at the following website:
      http://www.bioss.sari.ac.uk/~dirk/Supplements/

PMID- 15572474
TI  - Quantile smoothing of array CGH data.
AB  - MOTIVATION: Plots of array Comparative Genomic Hybridization (CGH) data often
      show special patterns: stretches of constant level (copy number) with sharp jumps
      between them. There can also be much noise. Classic smoothing algorithms do not
      work well, because they introduce too much rounding. To remedy this, we introduce
      a fast and effective smoothing algorithm based on penalized quantile regression.
      It can compute arbitrary quantile curves, but we concentrate on the median to
      show the trend and the lower and upper quartile curves showing the spread of the
      data. Two-fold cross-validation is used for optimizing the weight of the
      penalties. RESULTS: Simulated data and a published dataset are used to show the
      capabilities of the method to detect the segments of changed copy numbers in
      array CGH data.

PMID- 15572475
TI  - MapLinker: a software tool that aids physical map-linked whole genome shotgun
      assembly.
AB  - MapLinker is an analysis tool, as well as a browsing interface, that facilitates
      integration of whole genome sequence assembly with a clone-based physical map.
      Using the locations of sequence markers on the physical map, MapLinker generates
      a tentative sequence map of the genome that serves to verify the map and to guide
      genome-wide finishing.

PMID- 15572476
TI  - Metabolic pathway analysis web service (Pathway Hunter Tool at CUBIC).
AB  - MOTIVATION: Pathway Hunter Tool (PHT), is a fast, robust and user-friendly tool
      to analyse the shortest paths in metabolic pathways. The user can perform
      shortest path analysis for one or more organisms or can build virtual organisms
      (networks) using enzymes. Using PHT, the user can also calculate the average
      shortest path (Jungnickel, 2002 Graphs, Network and Algorithm. Springer-Verlag,
      Berlin), average alternate path and the top 10 hubs in the metabolic network. The
      comparative study of metabolic connectivity and observing the cross talk between
      metabolic pathways among various sequenced genomes is possible. RESULTS: A new
      algorithm for finding the biochemically valid connectivity between metabolites in
      a metabolic network was developed and implemented. A predefined manual assignment
      of side metabolites (like ATP, ADP, water, CO(2) etc.) and main metabolites is
      not necessary as the new concept uses chemical structure information (global and
      local similarity) between metabolites for identification of the shortest path.

PMID- 15572479
TI  - Should refusal to undergo a cesarean delivery be a criminal offense?

PMID- 15572480
TI  - First-trimester nasal bone evaluation for aneuploidy in the general population.
AB  - OBJECTIVE: To evaluate the role of fetal nasal bone imaging at 10 3/7 to 13 6/7
      weeks as a screening tool for aneuploidy, in a prospective multicenter trial.
      METHODS: Unselected patients from the general population with viable singleton
      pregnancies at 10 3/7 to 13 6/7 weeks were recruited at 15 U.S. centers. All had
      screening with nuchal translucency (NT) ultrasound by specially trained
      sonographers. In the last 8 months of this trial, first trimester nasal bone
      evaluation was added to the screening protocol. Nasal bones were described as
      present, absent, or unable to determine. RESULTS: A total of 38,189 patients
      completed first trimester NT screening, of whom 6,324 also underwent nasal bone
      sonography. An acceptable nasal image was obtained in 4,801 cases (76%), with
      nasal bones described as present in 4,779 (99.5%), and absent in 22 (0.5%). There
      were 11 identified cases of trisomy-21 in the population of 6,324 patients. In 9
      of the 11 cases (82%) the nasal bones were described as present, and 2 cases were
      described as unable to determine. The only other aneuploidies were 2 cases of
      trisomy-18, in 1 of which the nasal bones were described as absent, and in 1
      present. Absence of nasal bones had sensitivity for aneuploidy of 7.7%, false
      positive rate 0.3%, and positive predictive value 4.5%. CONCLUSION: First
      trimester nasal bone evaluation was not a useful test for population screening
      for trisomy-21 and added little to first-trimester NT screening. The difficulty
      in performing first-trimester nasal bone sonography consistently, in the general
      population setting, will significantly limit the usefulness of this aneuploidy
      screening technique.

PMID- 15572481
TI  - The association between fetal nasal bone hypoplasia and aneuploidy.
AB  - OBJECTIVE: To determine the association between fetal nasal bone hypoplasia and
      aneuploidy in women undergoing prenatal diagnosis. METHODS: A prospective cohort
      study involving women undergoing chorionic villus sampling and amniocentesis for
      an increased risk of aneuploidy. Fetal biometric and nasal bone measurements were
      obtained at the time of prenatal diagnosis and compared with karyotypes. Nasal
      bone hypoplasia was defined as nasal bone less than 2.5th percentile for the
      gestational age. RESULTS: A total of 632 fetuses were evaluated. Twenty-nine
      (4.6%) had an aneuploidy (18 trisomy 21, 5 trisomy 18, 1 Turner's syndrome, one
      Marker chromosome 1, 2 sex chromosome anomalies, and 2 triploidy). Nasal bone
      measurements were documented in 29 aneuploid fetuses. The nasal bone was either
      absent or hypoplastic in 12 of 29 (41%) fetuses with aneuploidy and in 8 of 18
      (44%) with trisomy 21. By using receiver operating characteristics curves, the
      optimal threshold of nasal bone hypoplasia associated with fetal aneuploidy was a
      biparietal diameter/nasal bone ratio of 11 or greater. The sensitivity,
      specificity, and positive and negative predictive values for the detection of
      fetal aneuploidy were 50%, 93%, 24%, and 98%, respectively. CONCLUSION: Absent or
      hypoplastic nasal bone is a marker for fetal aneuploidy in a high-risk
      population. However, this marker needs to be evaluated by larger prospective
      studies in low-risk populations before adoption for clinical use.

PMID- 15572482
TI  - Melissa Rowland and the rights of pregnant women.
AB  - On March 11, 2004, the State of Utah charged Melissa Rowland with the murder of
      her stillborn fetus, claiming that the death resulted from her rejection of the
      advice of her physicians to have a cesarean delivery. Although Ms. Rowland
      avoided the homicide charge by pleading guilty to lesser child endangerment
      charges, the approach taken by the State raises important and troubling issues
      regarding the autonomy rights of pregnant women, as well as their right to speak
      on behalf their unborn children. We use this case to review relevant ethical
      principals and legal precedents. We conclude that if Ms. Rowland is to be judged
      legally culpable for the death of her fetus, then the courts must first create a
      new and significant exception to the doctrine of informed consent and the common
      law and constitutional principles upon which it is based. Such a precedent could
      introduce a substantial disparity between the rights of pregnant women and those
      of all other persons. We would argue that a better means of assuring the health
      interests of the pregnant woman and the fetus in similar circumstances is through
      advocacy by obstetricians for pregnant women's fully realized rights, including
      the right to informed consent.

PMID- 15572483
TI  - The effect of common clinical contaminants on amniotic fluid fluorescence
      polarization results.
AB  - OBJECTIVE: To determine the effect of blood, meconium, and vaginal secretions on
      amniotic fluid (AF) fluorescence polarization results. METHODS: Amniotic fluid
      was collected by transabdominal amniocentesis from women at 20-41 weeks of
      gestation and contaminated with blood, meconium, and vaginal secretions to
      concentrations of 0.5, 1, 2, 5, and 10%. An additional 20% concentration was
      performed with meconium and vaginal secretions. Fluorescence polarization was
      determined by a TDx Analyzer with the NBD-PC fluorescent probe. Results were
      compared for each contaminant by concentration level using repeated-measures
      analysis of variance. RESULTS: Forty-eight samples from women at a mean
      gestational age of 35 weeks (range 20-41.5 weeks) were evaluated. Before
      contamination, 16 (33%) samples had fluorescence polarization values greater than
      290 mPol (immature), 10 (21%) were 260- 289 mPol (transitional), and 22 (46%)
      were less than 260 mPol (mature). Contamination with blood significantly altered
      fluorescence polarization values in AF samples with baseline values in the
      immature and mature categories such that values trended toward the transitional
      range. Contamination of baseline immature samples with vaginal secretions at 20%
      contamination level resulted in more mature fluorescence polarization values.
      Contamination with meconium more than 2% in the baseline immature category or
      more than 20% in the baseline transitional category also resulted in
      significantly more mature fluorescence polarization values. CONCLUSION: Amniotic
      fluid contamination with blood can result in more transitional range fluorescence
      polarization values, whereas contamination with meconium and vaginal secretions
      can result in more mature fluorescence polarization values.

PMID- 15572484
TI  - Fulminant sepsis after invasive prenatal diagnosis.
AB  - BACKGROUND: Sepsis is extremely rare after invasive prenatal diagnosis. CASE: A
      patient, who had undergone amniocentesis at 15 weeks, cordocentesis at 20 weeks,
      and repeat cordocentesis 24 hours before presentation, was admitted at 21 weeks
      gestation with vaginal bleeding, rupture of membranes, and intrauterine demise.
      Although clinical and laboratory findings were unremarkable at presentation, she
      rapidly developed septic syndrome with disseminated intravascular coagulation and
      eventually multiple organ failure. The fetus was disintegrated and the uterus had
      to be removed. She was discharged from the intensive care unit after 34 days.
      Cultures of the uterine content grew Clostridium perfringens. Review of the
      literature revealed 10 more cases of sepsis after transabdominal prenatal
      diagnosis. CONCLUSION: Sepsis after prenatal diagnosis can be devastating, unless
      promptly diagnosed and treated.

PMID- 15572485
TI  - Laparoscopic Burch colposuspension versus tension-free vaginal tape: a randomized
      trial.
AB  - OBJECTIVE: To compare the laparoscopic Burch colposuspension with the tension
      free vaginal tape procedure (TVT) for efficacy. METHODS: Seventy-two women from 2
      institutions were randomized: 36 to laparoscopic Burch colposuspension and 36 to
      TVT. Multichannel urodynamic tests were performed preoperatively and 1 year after
      surgery. A research nurse administered the Urogenital Distress Inventory,
      Incontinence Impact Questionnaire, and pelvic examinations using the pelvic organ
      prolapse quantification system preoperatively, and at 6 months, 1 year, and 2
      years after surgery. Voiding diaries were collected at 1 and 2 years. Primary
      outcome was objective cure, which was defined as no evidence of urinary leakage
      during postoperative urodynamic studies. Secondary outcomes included subjective
      continence, perioperative and postoperative data, and quality of life. RESULTS:
      Thirty-three laparoscopic Burch colposuspension and 33 TVT patients were analyzed
      with a mean follow-up of 20.6 +/- 8 months (range 12-43). Mean operative time was
      significantly greater in the laparoscopic Burch colposuspension group compared
      with the TVT group, 132 versus 79 minutes, respectively (P = .003). Multichannel
      urodynamic studies in 32 laparoscopic Burch colposuspension and 31 TVT patients
      showed a higher rate of urodynamic stress incontinence at 1 year in the
      laparoscopic Burch colposuspension group, 18.8% versus 3.2% (P = .056). There was
      a significant improvement in the number of incontinent episodes per week and in
      Urogenital Distress Inventory and Incontinence Impact Questionnaire scores in
      both groups at 1 and 2 years after surgery (P < .001). However, postoperative
      subjective symptoms of incontinence (stress, urge, and any urinary incontinence)
      were reported significantly more often in the laparoscopic Burch colposuspension
      group than in the TVT group (P < .04 for each category). CONCLUSION: The TVT
      procedure results in greater objective and subjective cure rates for urodynamic
      stress incontinence than does laparoscopic Burch colposuspension.

PMID- 15572486
TI  - Seven-year follow-up of the tension-free vaginal tape procedure for treatment of
      urinary incontinence.
AB  - OBJECTIVE: To evaluate the long-term cure rates and late complication rates after
      treatment of female urinary stress incontinence with the minimally invasive
      tension-free vaginal tape operation. METHODS: Prospective observational, 3-center
      cohort study originally of 90 women requiring surgical treatment for primary
      urinary stress incontinence. Assessment variables included a 24-hour pad weighing
      test, a stress test, visual analog scale for assessing the degree of bother, and
      a questionnaire assessing the subjective perception of the women on their
      continence status. RESULTS: The follow-up time was a mean of 91 months (range 78
      100 months). Both objective and subjective cure rates were 81.3% for the 80 women
      available for follow-up. Asymptomatic pelvic organ prolapse was found in 7.8%, de
      novo urge symptoms in 6.3%, and recurrent urinary tract infection in 7.5% of the
      women. No other long-term adverse effects of the procedure were detected.
      CONCLUSION: The tension-free vaginal tape procedure for treatment of female
      urinary stress incontinence is effective over a period of 7 years.

PMID- 15572487
TI  - Prevalence of persistent and de novo overactive bladder symptoms after the
      tension-free vaginal tape.
AB  - OBJECTIVE: The purpose of this study was to assess 1) the proportion of de novo
      urge incontinence and overactive bladder symptoms after a tension-free vaginal
      tape (TVT), and 2) the natural history of preoperative urge incontinence and
      overactive bladder symptoms after a TVT. METHODS: A chart review was performed on
      all patients who underwent a TVT without concomitant procedures from November
      1998 to November 2002. Preoperative and postoperative stress and mixed urinary
      incontinence symptoms as well as overactive bladder symptoms were assessed
      subjectively, as was the use of anticholinergics to treat overactive bladder
      symptoms. Two preoperative and postoperative validated quality-of-life
      questionnaires, the Incontinence Impact Questionnaire (IIQ-7) and Urinary
      Distress Inventory (UDI-6), were also compared. RESULTS: Ninety-eight patients
      were included in the study. Postoperatively, de novo urge incontinence symptoms
      developed in 9.1%, de novo overactive bladder symptoms developed in 4.3%, and
      8.7% started taking anticholinergics for the first time. After a TVT, the urge
      component resolved in 63.1% of those with preoperative symptoms of mixed
      incontinence, overactive bladder symptoms resolved in 57.3% of those with
      preoperative overactive bladder symptoms, and 57.7% of those who used
      anticholinergics preoperatively no longer needed to do so. There was also a
      statistically significant improvement in comparing the preoperative and
      postoperative IIQ-7 and UDI-6 scores. CONCLUSION: The proportion of patients in
      whom de novo overactive bladder or urge incontinence symptoms developed
      postoperatively is low, and approximately 57% of patients with preoperative
      overactive bladder symptoms can expect resolution of these symptoms after a TVT.

PMID- 15572488
TI  - Lateral excision of tension-free vaginal tape for the treatment of iatrogenic
      urethral obstruction.
AB  - OBJECTIVE: To report our experience on lateral excision of tape in women with
      iatrogenic urethral obstruction after the tension-free vaginal tape (TVT)
      procedure. METHODS: Seven women had iatrogenic urethral obstruction based on
      their clinical and urodynamic findings. All underwent lateral excision of the
      tape using the vaginal approach. Lower urinary tract symptoms, postvoid residual
      volume and urodynamic data were evaluated before and after excision. RESULTS:
      Before excision, all subjects had either irritative symptoms or increased
      postvoid residual volume (more than 100 mL), and 6 (85.7%) voided with strain.
      The mean time from initial surgery to tape excision was 28 days (range 4 to 108),
      with an average follow-up of 32 months (range 24-39). After the excision, voiding
      dysfunction was resolved in 6 of 7 patients. The remaining patient had
      significant improvement with only occasional symptoms of irritation. Two (28.6%)
      women reported recurrent stress incontinence and 1 (14.3%) required surgical
      treatment. The intervals for the 2 recurrent patients from TVT to excision were 4
      days. The intervals for the 5 continent women were 15 to 108 days. CONCLUSION:
      Urethral obstruction after TVT is a relatively uncommon condition. It can be
      effectively treated with transvaginal lateral excision of the tape. Recurrent
      stress incontinence seems to be less likely to occur when the takedown procedure
      occurs beyond 14 days after the initial TVT operation.

PMID- 15572489
TI  - Necrotizing surgical site infection after tension-free vaginal tape.
AB  - BACKGROUND: Infectious morbidity after tension-free vaginal tape (TVT) treatment
      of urinary stress incontinence may be a potential concern. CASE: A 53-year-old
      obese woman with a 7-year history of urinary incontinence consented to TVT
      placement. Two days after discharge the patient presented with suspected
      cellulitis. Dicloxacillin, ciprofloxacin, ampicillin/sulbactam, and metronidazole
      were ineffective. Removal of the tape, surgical debridement, dressing changes,
      ceftriaxone, and clindamycin followed by levofloxacin and metronidazole, repeat
      wound debridement, and vacuum assisted closure were required. Frozen section
      revealed gangrenous soft tissue with areas of skin necrosis, but no fasciitis.
      CONCLUSION: This is the first case of necrotizing surgical site infection after
      TVT placement. Infectious morbidity risks need to be considered in these
      procedures.

PMID- 15572490
TI  - The effect of ephedrine on intrapartum fetal heart rate after epidural analgesia.
AB  - OBJECTIVE: Adverse fetal heart rate (FHR) changes occur frequently during the
      first 30 minutes after epidural analgesia. The aim of this study was to estimate
      whether intravenous administration of ephedrine during induction of epidural
      analgesia can reduce the frequency of adverse FHR changes. METHODS: We
      prospectively studied 145 term singleton deliveries where epidural analgesia was
      administered. The patients were randomly allocated before the administration of
      epidural analgesia to receive an intravenous infusion of 10 mg ephedrine, after
      epidural induction, followed by a continuous infusion for 60 minutes of 20 mg
      ephedrine (study group) or to receive no ephedrine (control group). The FHR
      tracing was evaluated for 20 minutes before and 40 minutes after initiating
      epidural analgesia. Demographic data and clinical and delivery outcome were
      assessed and compared between the 2 groups. RESULTS: Injection of ephedrine
      significantly reduced the rate of major FHR changes appearing 15-25 minutes after
      induction of epidural analgesia in the study group compared with the control
      group (2/72 compared with 11/73, respectively; P = .009). To avoid 1 case of
      adverse FHR changes, 6.8 women should be treated with ephedrine. Maternal and
      fetal characteristics and outcome and mode of delivery were similar in the 2
      groups. Mean arterial pressure was significantly higher in the study group from
      the time of analgesia induction and during the subsequent 25 minutes. Maternal
      heart rate was transiently reduced in the study group only. CONCLUSION: Ephedrine
      administration during the time of epidural analgesia initiation can reduce the
      frequency of adverse FHR changes commonly observed immediately afterward.

PMID- 15572491
TI  - Buccal misoprostol to decrease blood loss after vaginal delivery: a randomized
      trial.
AB  - OBJECTIVE: To assess the efficacy of buccal misoprostol to decrease bleeding
      after vaginal delivery. METHODS: This was a randomized study of patients between
      22 weeks and 42 weeks of gestation with anticipated vaginal delivery. Patients
      were given either a 200-mug misoprostol tablet or placebo in the buccal space at
      the time of cord clamping. A continuous dilute intravenous oxytocin infusion was
      given to all patients at delivery of the placenta. Postpartum hemorrhage was
      defined as blood loss exceeding 500 mL. Sample size calculations based on
      previous studies assumed a 13% incidence of postpartum hemorrhage in the control
      group. To show a statistically significant reduction of postpartum hemorrhage a
      total of 1,604 patients would be required in each group. RESULTS: A total of 848
      patients were enrolled and 756 randomly assigned, 377 in the misoprostol group
      and 379 in the placebo group. Demographic, antepartum, and intrapartum
      characteristics were similar between the groups. The incidence of postpartum
      hemorrhage, 3% compared with 5%, (relative risk 0.65, 95% confidence interval
      0.33-1.29, P = .22), mean estimated blood loss, 322 compared with 329 mL, (P =
      .45), and mean minutes of the third stage of labor, 6.7 compared with 6.9 (P =
      .52) were similar between the groups, misoprostol and placebo, respectively.
      Hemoglobin difference before and after delivery, need for second or third
      uterotonic agent, and all measured neonatal variables including birth weights,
      and umbilical cord pH were similar between the groups. CONCLUSION: Buccal
      misoprostol at cord clamping is no more effective than placebo in reducing
      postpartum hemorrhage.

PMID- 15572492
TI  - Twin-twin transfusion syndrome: a population-based study.
AB  - OBJECTIVE: To study the incidence and mortality and morbidity rates of twin-twin
      transfusion syndrome in a complete population-based cohort in Nova Scotia.
      METHODS: A population-based cohort study of all monochorionic diamniotic twin
      pregnancies of 20 weeks of gestation or longer born to Nova Scotia (Canada)
      residents between 1988 and 2000 was examined. The effect of gestational age
      adjustment and birth weight discordancy of more than 20% on mortality and 1-year
      survival was studied. Other outcomes studied included birth depression,
      respiratory distress syndrome, chronic lung disease, interventricular hemorrhage,
      periventricular leukomalacia, acute renal failure, and congestive heart failure.
      RESULTS: Of 404 monochorionic-diamniotic twin pregnancies examined, 48 were
      identified with twin-twin transfusion syndrome. Total mortality rates per
      pregnancy were significantly greater in the twin-twin transfusion syndrome group
      than in the remainder of our monochorionic diamniotic population (P < .01).
      However, when adjusted for gestational age, mortality failed to achieve
      statistical significance. Similarly, no differences were noted for 1-year
      survival and other outcomes of liveborn infants after gestational age adjustment.
      Discordance in birth weight predicted a higher incidence of morbid outcomes per
      pregnancy, but this effect was lost after gestational age adjustment. CONCLUSION:
      Increased morbidity and mortality of twins with twin-twin transfusion syndrome is
      likely to be due to a higher incidence of preterm birth. Birth weight discordancy
      was not found to be an independent predictor of mortality after controlling for
      gestational age and twin-twin transfusion syndrome.

PMID- 15572493
TI  - Prenatal diagnosis of a trauma-related fetal epidural hematoma.
AB  - BACKGROUND: Prenatal diagnosis of fetal intracranial hemorrhage has important
      etiologic, management, and prognostic implications. Ultrasonography and magnetic
      resonance imaging (MRI) have been used to identify and evaluate this condition.
      We present the first reported case of epidural hematoma diagnosed prenatally.
      CASE: A 25-year-old para 3 was referred for evaluation of a suspected fetal
      intracranial abnormality following an alleged assault. Ultrasonography and MRI
      were used to diagnose an epidural hematoma prenatally. The fetus subsequently
      died in utero. Autopsy confirmed the presence of an epidural hematoma.
      CONCLUSION: Ultrasonography and MRI were useful in diagnosing a fetal epidural
      hematoma. Unfortunately, no known effective in utero therapy exists for this rare
      problem.

PMID- 15572494
TI  - Fetal hyperinsulinism and maternal one-hour postload plasma glucose level.
AB  - OBJECTIVE: Fetal insulin concentrations reflect the intrauterine glucose load
      given the fetus by the mother. In this study, we assessed the association between
      maternal glucose levels during oral glucose tolerance testing and fetal cord
      insulin. METHODS: Pregnant women with an oral glucose tolerance test (OGTT)
      result were included in this prospective study. The patients were divided into 3
      groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL
      (control, group I), 160-179 mg/dL (intermediate, group II), and gestational
      diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin
      therapy if blood glucose levels were not in the preferable range. RESULTS: Of the
      930 patients who entered the study, 570 (61.3%) were assigned to group I, 76
      (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value
      was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8
      microU/mL; range, 3-130 microU/mL) than in group I (median, 7.25 microU/mL;
      range, < 3-98 microU/mL). Cord blood insulin values were higher, albeit not
      significantly (P = .100, Mann-Whitney test), in group II than in group III
      (median, 9.9 microU/mL; range, < 3-61 microU/mL). CONCLUSION: Children whose
      mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher
      cord blood insulin values than offspring of women with a 1-hour value below 160
      mg/dL.

PMID- 15572495
TI  - A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency
      contraception.
AB  - OBJECTIVE: To compare the efficacy, patient acceptability and adverse effects of
      low-dose mifepristone (10 mg) with the levonorgestrel regimen (2 doses of 750
      microg given 12 hours apart) for emergency contraception. METHODS: This
      randomized controlled trial compared mifepristone (10 mg) to levonorgestrel (2
      doses of 750 microg given 12 hours apart) in the context of emergency
      contraception within 120 hours of unprotected intercourse. The primary outcome
      measure was unintended pregnancy. Secondary outcomes included adverse effects
      experienced by women, acceptability of the method of emergency contraception
      used, and the timing of the first menstrual cycle after treatment. RESULTS: The
      total number of women recruited was 2,065. The crude pregnancy rates were 1.3%
      and 2.0% for mifepristone and levonorgestrel (P = .46), with 77% and 64% of
      expected pregnancies prevented, respectively. Women receiving mifepristone were
      more likely to have a delayed onset of the subsequent menstrual cycle after
      treatment (P < .001), whereas those having levonorgestrel were more likely to
      have an early onset of the subsequent menstrual cycle (P < .001). Acceptability
      levels were high for both methods, with 94% of women receiving mifepristone and
      91% receiving levonorgestrel expressing satisfaction. There was no difference in
      adverse effects (nausea, vomiting, breast tenderness, abdominal pain, lethargy,
      headache, hot flushes, and dizziness) experienced by women in the 2 groups.
      CONCLUSION: This study suggests that a small dose of mifepristone is not less
      effective than levonorgestrel for emergency contraception. Both regimens were
      highly acceptable to women.

PMID- 15572496
TI  - Long-term treatment of menorrhagia with levonorgestrel intrauterine system versus
      endometrial resection.
AB  - OBJECTIVE: The purpose of this study was to compare the long-term efficacy of the
      levonorgestrel intrauterine system and transcervical resection of the endometrium
      in the treatment of menorrhagia. METHODS: This study was an open, randomized 3
      year trial. Patients with menorrhagia were assigned randomly to either the
      levonorgestrel intrauterine system (n = 30) or endometrial resection (n = 29).
      Pictorial blood loss assessment charts were used to measure menstrual blood loss.
      A pictorial blood-loss assessment chart score exceeding 75 (representing
      menstrual blood loss >/=60 mL) was used to diagnosis the patient as having
      menorrhagia. Discontinuations and cases requiring repeat operations were
      evaluated. RESULTS: Pictorial blood loss scores decreased from a baseline median
      of 261.5 (range, 60-1503) to 7 (range, 0-101; P < .001) for the levonorgestrel
      intrauterine system and from 311 (range, 81-2506) to 4 (range, 0-182; P < .001)
      for transcervical resection of the endometrium. Nineteen women of 30 using the
      levonorgestrel intrauterine system completed the 3-year follow-up compared with
      22 of 29 for transcervical resection of the endometrium. CONCLUSION: Both
      treatments efficiently reduced menstrual bleeding. The high continuation rate
      suggests that the levonorgestrel intrauterine system is comparable with
      transcervical resection of the endometrium.

PMID- 15572497
TI  - Accuracy of subjective hot flush reports compared with continuous sternal skin
      conductance monitoring.
AB  - OBJECTIVE: To compare 2 subjective and 1 objective method for assessing hot flush
      frequency: prospective paper hot flush diaries, prospective electronic event
      markers, and the Biolog ambulatory sternal skin conductance monitor. METHODS:
      Fifty-five breast cancer survivors provided two 24-hour periods of data, 1 week
      apart, at baseline before being randomized for an intervention study. Women
      completed a prospective paper hot flush diary and pressed an event marker to
      subjectively record each hot flush they experienced while wearing a sternal skin
      conductance monitor. RESULTS: Sensitivity was uniformly low (< 50%) for both
      subjective methods at each week. The estimated probability that a woman would
      record a true monitor-verified hot flush subjectively by diary or event marker
      was between 36% and 50% of the time if she was awake and between 22% and 42% of
      the time if she was asleep. Underreporting of diary hot flushes consequently
      resulted in more than 50% missing severity and bother ratings. Specificity was
      high (96-98%) for both the diary and event marker, for both weeks, and for both
      waking and sleeping times. The positive predictive value was low (34-52%), and
      negative predictive value was high (94-97%). This indicates that, rather than
      overreporting hot flushes when they did not exist, women tended to underreport
      hot flushes when they did exist. CONCLUSION: Use of prospective paper hot flush
      diaries and electronic event markers may seriously underestimate hot flush
      frequency and result in missed intensity and bother ratings.

PMID- 15572498
TI  - Does urinary incontinence affect middle-aged and older women's time use and
      activity patterns?
AB  - OBJECTIVE: To investigate the relationship between urinary incontinence and
      women's levels and hours of participation in 31 activities. METHODS: A subset of
      panel members from the Health and Retirement Study completed the self
      administered Consumption and Activities Mail Survey questionnaire in 2001. These
      data were linked with Health and Retirement Study 2000 data. Analyses were
      limited to 2,190 female Consumption and Activities Mail Survey self-respondents
      born in 1947 or earlier. Logistic regression was used to predict activity
      participation. Linear regression was used to predict the number of hours of
      participation. RESULTS: The hypothesis that urinary incontinence affects women's
      time use and activity patterns was supported. Compared with the continent women,
      the incontinent women were less likely to have house cleaned, shopped, physically
      shown affection, or attended religious services in the recent past; and were more
      likely to have watched television or made music by singing or playing an
      instrument. Compared with continent activity participants, incontinent
      participants reported significantly fewer hours spent walking, communicating with
      friends and family by telephone or e-mail, working for pay, using a computer, and
      engaging in personal grooming and hygiene. CONCLUSION: These findings
      substantiate prior work on the relationship between urinary incontinence and
      quality of life, and suggest a useful route for educating patients about the
      impact of urinary incontinence. Clinicians must be alert to opportunities for
      encouraging incontinent women to be active. It is also important to consider the
      implications for time use and activity patterns when advising patients about
      treatment and management options. LEVEL OF EVIDENCE: II-2.

PMID- 15572499
TI  - Local analgesia in laparoscopy: a randomized trial.
AB  - OBJECTIVE: To investigate whether local infiltration of bupivacaine reduces
      postoperative pain at trocar sites during gynecologic laparoscopy. METHODS: This
      was a randomized, placebo-controlled, double-blind clinical trial, using patients
      as their own controls. For each patient, 2 opposite trocar sites were
      infiltrated. One site was randomly chosen to receive 0.5% bupivacaine, and the
      other received 0.9% saline. In addition, patients were randomized into 2 cohorts
      to receive either preincision or postsurgical infiltration. Surgeons, patients,
      and interviewers were blinded toward the exposure. Postoperative pain was
      evaluated at 1 hour, 4 hours, and 24 hours after surgery using a 100-mm visual
      analog scale. Patients rated their pain at each of the infiltrated trocar sites.
      A 20-mm difference between pain scores was considered clinically significant. A
      paired t test was used for analysis. RESULTS: Infiltration of bupivacaine at
      completion of surgery resulted in significantly decreased pain at 1 hour
      postoperatively (mean pain score 25.8 versus 48.6, P = .02). Mean pain scores at
      4 hours and 24 hours were decreased, but not statistically different. Patients
      receiving bupivacaine before surgery did not have a statistically significant
      decrease in pain scores. CONCLUSION: Infiltration of bupivacaine at completion of
      gynecologic laparoscopic surgery decreases pain at trocar sites in the immediate
      postoperative period.

PMID- 15572500
TI  - Vaginal apex resection: a treatment option for vaginal apex pain.
AB  - OBJECTIVE: Vaginal apex pain is a subset of chronic pelvic pain commonly treated
      with surgical excision of the vaginal apex. Our objective was to estimate long
      term postoperative pain levels, recovery time, and return to sexual function in
      women who have undergone vaginal apex repair for chronic vaginal apex pain.
      METHODS: Since 1995, 45 women have undergone vaginal apex repair at our
      institution. All were asked to complete a questionnaire describing pain levels,
      sexual function, daily activities, ability to work, and medical therapy before
      and after surgical repair of the vaginal apex. Demographic background, previous
      medical history, and surgical history were abstracted from the medical records.
      Fisher exact and Wilcoxon rank sum tests were used to determine associations
      among baseline characteristics and various outcomes. McNemar chi(2) testing was
      use to compare before and after pain levels. RESULTS: Twenty-seven women
      constituted the study sample and were available for evaluation before and after
      vaginal apex repair. Sixty-seven percent of respondents experienced resolution of
      pelvic pain after vaginal apex repair for a median of 20 months. The number of
      women experiencing pain with daily activities decreased from 92% before vaginal
      apex repair to 41% after vaginal apex repair, and 30% reported sexual activity
      without dyspareunia after vaginal apex repair (P = .004). Sixty-one percent of
      women returned to work after vaginal apex repair. Most patients required
      continued medical therapy after vaginal apex repair. CONCLUSION: Vaginal apex
      repair improves general levels of pelvic pain in some patients diagnosed with
      vaginal apex pain. Pain relief after vaginal apex repair is temporary, and women
      are likely to need continued medical therapy.

PMID- 15572501
TI  - Psychological and sociocultural perspectives on follow-up of abnormal
      Papanicolaou results.
AB  - OBJECTIVE: To understand women's motivation to attend follow-up of an abnormal
      Papanicolaou (Pap) test by applying a general theoretical framework for voluntary
      behavior. METHODS: Semistructured, face-to-face interviews were conducted among
      120 low-income, African-American, Caucasian, or Hispanic outpatients, aged 25-50
      years, who presented for routine gynecologic care. Interview questions assessed
      social, cognitive, environmental, and emotional factors surrounding follow-up for
      an abnormal Pap test. Content analysis was performed. RESULTS: The majority of
      women (74%) described their attitude toward returning for a follow-up visit as
      favorable. Overall, knowledge regarding the significance of an abnormal result
      was poor, and misconceptions were common. Perceived barriers, consequences, and
      social influences associated with attending follow-up were qualitatively
      different across the 3 racial/ethnic groups. For example, African-American and
      Hispanic women expressed embarrassment more frequently than Caucasian women and
      were less likely to anticipate obstacles to attending follow-up. Furthermore,
      African-American women were the least likely to be influenced by others' opinions
      and to perceive difficulty in adhering to follow-up recommendations. For nearly
      all women, adequate communication with their provider was a key component of
      anticipated adherence. CONCLUSION: Clinicians may exert a positive influence on
      adherence among patients who experience an abnormal Pap test by engaging patients
      in a dialogue that accommodates the patient's sociocultural environment, explores
      concerns regarding the partner's reaction, emphasizes the importance of follow
      up, provides a clear understanding of the process and timeline surrounding follow
      up recommendations, and encourages the patient to anticipate obstacles to
      adherence and assists with solutions.

PMID- 15572502
TI  - Social and cultural barriers to Papanicolaou test screening in an urban
      population.
AB  - OBJECTIVE: To define screening behaviors, attitudes, and beliefs regarding cancer
      and its treatment among women with cervical cancer. METHODS: Between August 2000
      and July 2002, 148 consecutive women with invasive cervical cancer were queried
      about barriers to screening. Women presented to outpatient clinics, emergency
      departments, or inpatient units of 3 urban hospitals. Two groups of women were
      identified: those who denied having had a Papanicolaou (Pap) test and those who
      had recalled having Pap test in the past. Responses were compared using t tests,
      chi(2) tests, and binary logistic regression. RESULTS: The 146 (99%) respondents
      were predominantly African Americans (50%) or Hispanic (27%). Thirty-six (25%)
      women reported no prior screening. Women never screened were significantly more
      likely to be Hispanic (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.4
      6.7), recent immigrants (OR 5.7, 95% CI 2.0-16), less educated (OR 3.6, 95% CI
      1.6-8.0), and uninsured (OR 3.9, 95% CI 1.6-9.7). They were more likely to lack
      family support (adjusted OR 3.5, 95% CI 1.1-11) and lack knowledge about their
      risk for cervical cancer (adjusted OR 2.6, 95% CI 1.1-6.4). Unscreened women
      displayed fatalistic attitudes, believing cancer is bad luck (adjusted OR 2.6,
      95% CI 1.0-6.9) and not wanting to know they had cancer (adjusted OR 3.0, 95% CI
      1.0-9.4).. CONCLUSION: We have identified factors and beliefs that are barriers
      to Pap test screening in urban cervical cancer patients. Further studies should
      evaluate effects of addressing cultural, cognitive, and financial barriers on Pap
      test compliance.

PMID- 15572503
TI  - Teaching and assessing professionalism in medicine.
AB  - Professionalism is the single most important of the clinical competencies. Lack
      of professional behavior, in turn, is the single most common cause for
      disciplinary action against third and fourth-year medical students, residents,
      fellows, and clinical practitioners. Desirable professional attributes include
      humility, honesty, responsibility, reliability, and accountability. The ability
      to preserve an appropriate balance between patient care responsibilities and
      personal commitments also is an important feature of professional behavior.
      Altruism, respectfulness, loyalty, compassion, sensitivity, and tactfulness are
      other desirable professional attributes. In addition, professionalism requires a
      heightened sense of intellectual curiosity, insight into personal strengths and
      weaknesses, maturity, and commitment to clinical excellence and self-directed
      learning. Professionalism can be taught and assessed through lectures, small
      group seminars, role-playing exercises, directed reading, and one-on-one
      observation and counseling. However, the most effective way of teaching
      professionalism is for instructors to model appropriate behavior and to impose a
      consistent policy of zero tolerance for unprofessional behavior.

PMID- 15572504
TI  - World Health Organization systematic review of screening tests for preeclampsia.
AB  - OBJECTIVE: We sought to assess the usefulness of clinical, biophysical, and
      biochemical tests in the prediction of preeclampsia. DATA SOURCES: The sources of
      data we used to conduct this review included the computerized databases MEDLINE
      (1966 to February 2003), EMBASE, Popline, CINAHL, and LILACS plus reference
      lists, conference proceedings, textbooks, and contact with experts. METHODS OF
      STUDY SELECTION: All cohort or cross-sectional studies reporting data on the
      relationship between a predictive test that was performed during pregnancy and
      the development of preeclampsia were eligible for inclusion, whereas case-control
      studies were excluded. Eighty-seven (211,369 women) of 7,191 potentially relevant
      articles met inclusion criteria. We evaluated the methodologic quality for each
      included study. TABULATION, INTEGRATION, AND RESULTS: Using a standardized
      protocol, one reviewer selected and extracted data on study characteristics,
      quality, and accuracy. Data abstracted from each study were arranged in 2 x 2
      tables to construct receiver operating characteristics plots (sensitivity against
      1 - specificity) and pooled to produce summary likelihood ratios for positive and
      negative tests results. Moderate predictive accuracy of anticardiolipin
      antibodies, the presence of bilateral diastolic notches during Doppler
      ultrasonography, and urinary kallikrein were found in women at low risk of
      developing preeclampsia. Nevertheless, because the pretest probability of
      preeclampsia with a positive result was but minimally increased, the clinical use
      of these tests is limited. Other ultrasonography characteristics and the
      measurement of fetal and placental peptides showed low predictive accuracy. In
      populations that were deemed at high risk for preeclampsia, the use of Doppler
      ultrasonography had low predictive accuracy. No definitive conclusions were
      possible in the case of many other tests, because the number of studies that met
      the minimal inclusion criteria was limited. CONCLUSION: As of 2004, there is no
      clinically useful screening test to predict the development of preeclampsia.
      Further prospective, longitudinal studies are needed.

PMID- 15572505
TI  - Anal incontinence after vaginal delivery: a five-year prospective cohort study.
AB  - OBJECTIVE: The long-term prevalence of anal incontinence after vaginal delivery
      is unknown. The aim of the present study was to evaluate the prevalence of anal
      incontinence in primiparous women 5 years after their first delivery and to
      evaluate the influence of subsequent childbirth. METHODS: A total of 349
      nulliparous women were prospectively followed up with questionnaires before
      pregnancy, at 5 and 9 months, and 5 years after delivery. A total of 242 women
      completed all questionnaires. Women with sphincter tear at their first delivery
      were compared with women without such injury. Risk factors for development of
      anal incontinence were also analyzed. RESULTS: Anal incontinence increased
      significantly during the study period. Among women with sphincter tears, 44%
      reported anal incontinence at 9 months and 53% at 5 years (P = .002). Twenty-five
      percent of women without a sphincter tear reported anal incontinence at 9 months
      and 32% had symptoms at 5 years (P < .001). Risk factors for anal incontinence at
      5 years were age (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.0-1.2),
      sphincter tear (OR 2.3; 95% CI 1.1-5.0), and subsequent childbirth (OR 2.4; 95%
      CI 1.1-5.6). As a predictor of anal incontinence at 5 years after the first
      delivery, anal incontinence at both 5 months (OR 3.8; 95% CI 2.0-7.3) and 9
      months (OR 4.3; 95% CI 2.2-8.2) was identified. Among women with symptoms, the
      majority had infrequent incontinence to flatus, whereas fecal incontinence was
      rare. CONCLUSION: Anal incontinence among primiparous women increases over time
      and is affected by further childbirth. Anal incontinence at 9 months postpartum
      is an important predictor of persisting symptoms.

PMID- 15572506
TI  - Evaluation and treatment of women with rectocele: focus on associated defecatory
      and sexual dysfunction.
AB  - Pelvic organ prolapse is a common and growing condition for which women seek help
      and frequently undergo surgical management. Prolapse of the posterior vaginal
      wall, alone or in combination with other compartment defects, can be a challenge
      for the pelvic surgeon. A clear understanding of the normal anatomy, interactions
      of the connective tissue and muscular supports of the pelvis, and the
      relationship or lack of relationship between anatomy and function is required.
      Vaginal support defects occur with and without symptoms, and many of the symptoms
      attributed to pelvic organ prolapse can result from other causes. Pelvic
      pressure, the need to splint the perineum to defecate, impaired sexual relations,
      difficult defecation, and fecal incontinence are some of the symptoms that have
      been correlated with rectoceles. Whether the prolapse is the cause of these
      symptoms or is a result of straining and stretching of support tissues in women
      with defecation disorders is still unknown. We will present the current
      literature on these relationships and what evaluations are useful when caring for
      a woman with a rectocele and defecation disorders. Either pessaries or surgery
      can be used for treating rectoceles. Several surgical techniques have been
      described, including transvaginal, transanal, abdominal, and the use of graft
      materials to treat both anatomical defects and functional symptoms. The success,
      rationale, and complications of each approach, including anatomic cure, impact on
      defecation, and sexual function, are presented.

PMID- 15572508
TI  - Practice bulletin No. 53--Diagnosis and treatment of gestational trophoblastic
      disease.

PMID- 15572509
TI  - Fetal reduction from twins to a singleton: selective reduction or partial
      abortion?

PMID- 15572511
TI  - Fetal reduction from twins to a singleton: selective reduction or partial
      abortion?

PMID- 15572512
TI  - ACOG Practice Bulletin No. 58. Ultrasonography in pregnancy.

PMID- 15572515
TI  - ACOG Committee Opinion No. 306. Informed refusal.
AB  - Informed refusal is a fundamental component of the informed consent process.
      Informed consent laws have evolved to the "materiality or patient viewpoint"
      standard. A physician must disclose to the patient the risks, benefits, and
      alternatives that a reasonable person in the patient's position would want to
      know to make an informed decision. Throughout this process, the patient's
      autonomy, level of health literacy, and cultural background should be respected.
      The subsequent election by the patient to forgo an intervention that has been
      recommended by the physician constitutes informed refusal. Documentation of the
      informed refusal process is essential. It should include a notation that the need
      for the intervention, as well as risks, benefits, and alternatives to the
      intervention, and possible consequences of refusal, have been explained. The
      patient's reason for refusal also should be documented.

PMID- 15572516
TI  - ACOG Committee Opinion No. 307. Partner consent for participation in women's
      reproductive health research.
AB  - Recent advances in reproductive medicine include treatment of subfertility as
      well as investigation of agents that may serve as both contraceptives and
      potential prophylaxis against sexually transmitted diseases, including potential
      protection from human immunodeficiency virus (HIV). Although there is no doubt
      regarding the need for informed consent by women participating in trials
      evaluating the safety and effectiveness of these novel agents and treatments,
      there has been some debate regarding the necessity and propriety of requiring
      consent from the partners of women involved in certain types of clinical trials
      involving reproductive health. Issues of partner consent are unique to research
      surrounding women 's reproductive health as opposed to research pertaining to
      women's health, in general. This is due, in part, to a valid concern about a
      potential effect of the research on the partner. There are, therefore, legitimate
      reasons to obtain partner consent for a woman's participation in a clinical
      trial. In the absence of such reason, partner consent should not be mandated.

PMID- 15572517
TI  - ACOG Committee Opinion No. 308. The uninsured.
AB  - The United States is one of the.few industrialized nations in the world that does
      not guarantee access to health care for its population. Access to health care for
      all women is a paramount concern of obstetrician-gynecologists and the American
      College of Obstetricians and Gynecologists. Lack of health care coverage creates
      access issues that affect women, practitioners, and the health care system as a
      whole. The number of women in the United States without health care coverage grew
      3 times faster than the number of men without such coverage during the late 1990s
      and early 2000s. A change in our currently fragmented health care system is
      warranted because the lack of coverage clearly matters to the millions of
      uninsured Americans. Pregnant women and infants are among the most vulnerable
      populations in the country and the American College of Obstetricians and
      Gynecologists believes that providing them with fill insurance coverage must be a
      primary step in the process of providing coverage for all Americans. However, it
      is only the first step; it is critical to expand coverage for all Americans.
      Health professionals can play a pivotal role in improving access to needed health
      care by helping society understand the importance of broadening health insurance
      coverage.

PMID- 15572518
TI  - Src family kinase involvement in rat preglomerular microvascular contractile and
      [Ca2+]i responses to ANG II.
AB  - Experiments were performed to investigate the potential role of Src family
      kinase(s) in the rat afferent arteriolar contractile response to ANG II. The in
      vitro blood-perfused juxtamedullary nephron technique was employed to monitor
      afferent arteriolar lumen diameter responses to 1-100 nM ANG II before and during
      Src family kinase inhibition (10 microM PP2). PP2 did not alter baseline diameter
      but attenuated ANG II-induced contractile responses by 33 +/- 6%. An inactive
      analog of PP2 (PP3) had no effect on ANG II-induced afferent arteriolar
      contraction. The effect of Src kinase inhibition on ANG II-induced intracellular
      free Ca(2+) concentration ([Ca(2+)](i)) responses was probed in fura 2-loaded
      preglomerular microvascular smooth muscle cells (PVSMCs) obtained from explants
      and studied after 3-5 days in culture. In untreated PVSMCs, ANG II evoked peak
      (Delta = 293 +/- 66 nM) and plateau (Delta = 23 +/- 8 nM) increases in
      [Ca(2+)](i). In PVSMCs pretreated with PP2, baseline [Ca(2+)](i) was unaltered,
      but both the peak (Delta = 140 +/- 22 nM) and plateau (Delta = 3 +/- 2 nM) phases
      of the ANG II response were significantly reduced compared with untreated cells.
      PP3 did not alter [Ca(2+)](i) responses to ANG II. Immunoprecipitation and
      Western blot analysis confirmed that 100 nM ANG II increased phosphorylation of c
      Src (at Y(416)) in PVSMCs. The phosphorylation response was maximal 1 min after
      ANG II exposure and was prevented by PP2. We conclude that the preglomerular
      vasoconstriction evoked by ANG II involves rapid c-Src activation with subsequent
      effects that contribute to the [Ca(2+)](i) response to the peptide.

PMID- 15572519
TI  - AT2 receptors cross talk with AT1 receptors through a nitric oxide- and RhoA
      dependent mechanism resulting in decreased phospholipase D activity.
AB  - ANG II activation of phospholipase D (PLD) is required for ERK and NAD(P)H
      oxidase activation, both of which are involved in hypertension. Previous findings
      demonstrate that ANG II stimulates PLD activity through AT(1) receptors in a RhoA
      dependent mechanism. Additionally, endogenous AT(2) receptors in preglomerular
      smooth muscle cells attenuate ANG II-mediated PLD activity. In the present study,
      we examined the signal transduction mechanisms used by endogenous AT(2) receptors
      to modulate ANG II-induced PLD activity through either PLA(2) generation of
      lysophosphatidylethanolamine or Galpha(i)-mediated generation of nitric oxide
      (NO) and interaction with RhoA. Blockade of AT(2) receptors, Galpha(i) and NO
      synthase, but not PLA(2), enhanced ANG II-mediated PLD activity in cells rich in,
      but not poor in, AT(2) receptors. Moreover, NO donors, a direct activator of
      guanylyl cyclase and a cGMP analog, but not lysophosphatidylethanolamine,
      inhibited ANG II-mediated PLD activity, whereas an inhibitor of guanylyl cyclase
      augmented ANG II-induced PLD activity. AT(2) receptor- and NO-mediated
      attenuation of ANG II-induced PLD activity was completely lost in cells
      transfected with S188A RhoA, which cannot be phosphorylated on serine 188.
      Therefore, our data indicate that AT(2) receptors activate Galpha(i),
      subsequently stimulating NO synthase and leading to increased soluble guanylyl
      cyclase activity, generation of cGMP, and activation of a protein kinase,
      resulting in phosphorylation of RhoA on serine 188. Furthermore, because AT(2)
      receptors inhibit AT(1) receptor signaling to PLD via modulating RhoA activity,
      AT(2) receptor signaling can potentially regulate multiple vasoconstrictive
      signaling systems through inactivating RhoA.

PMID- 15572520
TI  - Translational regulation of vascular endothelial growth factor expression in
      renal epithelial cells by angiotensin II.
AB  - ANG II regulates growth factor expression in the kidney. We investigated whether
      ANG II regulated vascular endothelial growth factor (VEGF) synthesis in proximal
      tubular epithelial (MCT) cells. ANG II (1 nM) increased VEGF protein expression
      within 5 min, the effect lasting for 30 min. There was no change in VEGF mRNA
      levels or mRNA stability, and transcription inhibitors did not affect ANG II
      induced VEGF expression. Regulation of VEGF translation was investigated.
      Polyribosomal analysis revealed selective enrichment of heavy ribosomes
      (polysomes) with VEGF mRNA transcripts compared with light ribosomes in ANG II
      treated cells, although distribution of GAPDH was unaltered. In vitro translation
      of total RNA from polysomal fractions showed selective increase in VEGF protein
      synthesis in ANG II-treated cells. Preincubation with LY-294002, a PI 3-kinase
      inhibitor, or expression of dominant-negative Akt prevented ANG II-stimulated
      increase in VEGF translation. ANG II increased phosphorylation of eukaryotic
      initiation factor 4E and its binding protein 4E-BP1, critical events that
      regulate the initiation phase of protein translation. ANG II failed to increase
      VEGF mRNA translation in cells stably expressing the phosphorylation mutant of 4E
      BP1. Our data illustrate that a rapid increase in VEGF protein expression by ANG
      II is regulated at the initiation phase of translation of VEGF mRNA in renal
      epithelial cells. Regulation of VEGF translation by ANG II represents a novel
      pathway of renal response to injury.

PMID- 15572521
TI  - Lithium activates the Wnt and phosphatidylinositol 3-kinase Akt signaling
      pathways to promote cell survival in the absence of soluble survival factors.
AB  - Mouse proximal tubular cells (BUMPT), when cultured in the absence of growth
      factors, activate a default apoptotic pathway. Although Wnt signaling antagonizes
      the effect of proapoptotic triggers, its role in regulating the default pathway
      of apoptosis is less well defined. The present study examines the hypothesis that
      lithium (Li(+)) and (2'Z,3'E)-6-bromoindirubin-3'-oxime (BIO), two glycogen
      synthase kinase-3beta (GSK3beta) inhibitors, promote survival of growth factor
      deprived renal epithelial cells by activating the Wnt pathway. These studies
      demonstrate that Li(+) and BIO activate Wnt signaling as indicated by the
      following changes: phosphorylation (inhibition) of GSK3beta; decreased
      phosphorylation of beta-catenin (a GSK3beta substrate); nuclear translocation of
      beta-catenin; specific transcriptional activation of Tcf/catenin-responsive
      pTopflash constructs; and an increase in the expression of cyclin D1 (indicative
      of a promitogenic cell response). In addition, Li(+) or BIO significantly
      increases the phosphorylation (activation) of Akt, an anti-apoptotic protein, and
      inhibits apoptosis (decreases both annexin-V staining and caspase-3 activation),
      during serum deprivation. Inhibition of phosphatidylinositol 3-kinase
      (responsible for Akt activation) either by wortmanin or LY-294002 prevented Li(+)
      or BIO-induced Akt phosphorylation and reduces cell survival without altering
      the phosphorylation state of GSK3beta. Li(+) or BIO also increases the expression
      of insulin-like growth factor-II (IGF-II), a potent proliferative signaling
      protein. Li(+) or BIO-free conditioned medium harvested from Li(+)- or BIO
      exposed cells also induced Akt phosphorylation, mimicking the protective effect
      of the two GSK3beta inhibitors on serum-starved cells. Furthermore, the effect of
      conditioned medium on Akt phosphorylation could be inhibited by either LY-294002
      or IGF-binding protein. BIO, a specific GSK3beta inhibitor, replicated the
      protective effect of Li(+) on cell viability, suggesting that GSK3beta activation
      is important for initiating the apoptotic pathway. Taken together, these data
      suggest that Li(+) or BIO promotes renal epithelial cell survival by inhibiting
      apoptosis through GSK3beta-dependent activation of the Wnt pathway and subsequent
      release of IGF-II. Extracellular IGF-II serves as an autocrine survival factor
      that is responsible, in part, for activating the anti-apoptotic
      phosphatidylinositol-3-kinase-Akt pathway during serum deprivation.

PMID- 15572522
TI  - The gamma-subunit of Na-K-ATPase is incorporated into plasma membranes of mouse
      IMCD3 cells in response to hypertonicity.
AB  - Hypertonicity mediated by chloride upregulates the expression of the gamma
      subunit of Na-K-ATPase in cultured cells derived from the murine inner medullary
      collecting duct (IMCD3; Capasso JM, Rivard CJ, Enomoto LM, and Berl T. Proc Natl
      Acad Sci USA 100: 6428-6433, 2003). The purpose of this study was to examine the
      cellular locations and the time course of gamma-subunit expression after long
      term adaptation and acute hypertonic challenges induced with different salts.
      Cells were analyzed by confocal immunofluorescence and immunoelectron microscopy
      with antibodies against the COOH terminus of the Na-K-ATPase gamma-subunit or the
      gamma(b) splice variant. Cells grown in 300 mosmol/kgH(2)O showed no
      immunoreactivity for the gamma-subunit, whereas cells adapted to 600 or 900
      mosmol/kgH(2)O demonstrated distinct reactivity located at the plasma membrane of
      all cells. IMCD3 cell cultures acutely challenged to 550 mosmol/kgH(2)O with
      sodium chloride or choline chloride showed incorporation of gamma into plasma
      membrane 12 h after osmotic challenge and distinct membrane staining in
      approximately 40% of the cells 48 h after osmotic shock. In contrast, challenging
      the IMCD3 cells to 550 mosmol/kgH(2)O by addition of sodium acetate did not
      result in expression of the gamma-subunit in the membranes of surviving cells
      after 48 h. The present results demonstrate that the Na-K-ATPase gamma-subunit
      becomes incorporated into the basolateral membrane of IMCD3 cells after both
      acute hyperosmotic challenge and hyperosmotic adaptation. We conclude that the
      gamma-subunit has an important role in the function of Na-K-ATPase to sustain the
      cellular cation balance over the plasma membrane in a hypertonic environment.

PMID- 15572523
TI  - Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma
      demonstrated by breath-hold magnetic resonance spectroscopy.
AB  - Increased utilization of cross-sectional imaging has resulted in increased
      detection of incidental renal tumors. The noninvasive characterization of renal
      tissue has important implications for the diagnosis of renal malignancies and
      treatment monitoring. Recently, multiple breath-hold averaged proton magnetic
      resonance spectroscopy ((1)H-MRS) performed at high field has enabled the use of
      this noninvasive metabolic profiling technique for the investigation of the
      abdomen. Multiple breath-hold averaged (1)H-MRS at high field (3T) was obtained
      in the kidneys of 10 healthy volunteers and in renal cell carcinoma tumors of 14
      patients. The spectra of normal kidneys showed four main groups of resonances: 1)
      at 5.4-5.6 ppm, attributed to C6 of cholesterol and the unsaturated parts of the
      olefinic region of fatty acids; 2) at 4.7 ppm, attributed to the residual water
      signal; 3) at 3.2 ppm, attributed to trimethylamine moiety of choline
      metabolites; and 4) at 1.3 and 0.9 ppm, attributed to the methylenes and terminal
      methyls of lipids. The ratio of the signal at 5.4 ppm to that of 1.3 ppm was 19
      fold lower in renal cell carcinomas than in healthy kidneys, tied P = 0.0003 Mann
      Whitney U-test, suggesting a decrease in both free cholesterol and the degree of
      unsaturation of fatty acids in the malignant tissue. This metabolic shift is in
      agreement with previous ex vivo studies of human renal cell carcinoma. The
      ability to detect renal metabolic shifts noninvasively may improve the
      specificity of preoperative renal tissue characterization and may provide a new
      modality for treatment monitoring.

PMID- 15572524
TI  - Expression of endothelial nitric oxide synthase in developing rat kidney.
AB  - Endothelium-derived nitric oxide (NO) is synthesized within the developing kidney
      and may play a crucial role in the regulation of renal hemodynamics. The purpose
      of this study was to establish the expression and intrarenal localization of the
      NO-synthesizing enzyme endothelial NO synthase (eNOS) during kidney development.
      Rat kidneys from 14 (E14)-, 16 (E16)-, 18 (E18)-, and 20-day-old (E20) fetuses
      and 1 (P1)-, 3 (P3)-, 7 (P7)-, 14 (P14)-, and 21-day-old (P21) pups were
      processed for immunocytochemical and immunoblot analysis. In fetal kidneys,
      expression of eNOS was first observed in the endothelial cells of the
      undifferentiated intrarenal capillary network at E14. At E16, strong eNOS
      immunoreactivity was observed in the endothelial cells of renal vesicles, S
      shaped bodies (stage II glomeruli), and stage III glomeruli at the
      corticomedullary junction. At E18-20, early-stage developing glomeruli located in
      the subcapsular region showed less strong eNOS immunoreactivity than those of
      E16. The eNOS-positive immature glomeruli were observed in the nephrogenic zone
      until 7 days after birth. In fetal kidneys, eNOS was also expressed in the
      medulla in the endothelial cells of the capillaries surrounding medullary
      collecting ducts. After birth, eNOS immunostaining gradually increased in the
      developing vascular bundles and peritubular capillaries in the medulla and was
      highest at P21. Surprisingly, eNOS was also expressed in proximal tubules, in the
      endocytic vacuolar apparatus, only at P1. The strong expression of eNOS in the
      early stages of developing glomeruli and vasculature suggests that eNOS may play
      a role in regulating renal hemodynamics of the immature kidney.

PMID- 15572525
TI  - Gonadal steroid regulation of renal injury in renal wrap hypertension.
AB  - Renal injury is greater in male compared with female rats after renal wrap (RW)
      hypertension. We investigated the role of gonadal steroids in the sex differences
      in RW disease severity in male (M) and female (F), castrated (Cast), and
      ovariectomized (OVX) rats and after dihydrotestosterone (DHT) and 17beta
      estradiol (E2) treatment. Male castration attenuated the severity of RW-induced
      glomerulosclerosis (GS) [GS index (GSI): RW-M, 2.1 +/- 0.2; RW-Cast, 1.3 +/- 0.2;
      RW-Cast+DHT, 2.4 +/- 0.4], mean glomerular volume (MGV; microm3 x 10(6): RW-M,
      1.9 +/- 0.1; RW-Cast, 1.45 +/- 0.15; RW-Cast+DHT, 1.91 +/- 0.15), tubular damage,
      and proteinuria (mg/day: RW-M, 130 +/- 8; RW-Cast, 105 +/- 5; RW-Cast+DHT, 142 +/
      9), whereas DHT treatment abrogated these effects. Ovariectomy increased the GSI
      (RW-F, 0.69 +/- 0.05; RW-OVX, 1.2 +/- 0.1; RW-OVX+E2, 0.65 +/- 0.05), tubular
      damage, and MGV (microm3 x 10(6): RW-F, 1.0 +/- 0.06; RW-OVX, 1.5 +/- 0.05; RW
      OVX+E2, 0.96 +/- 0.06), whereas E2 treatment prevented these effects.
      Furthermore, DHT treatment of RW-OVX animals exacerbated the GSI (1.9 +/- 0.19),
      MGV (1.7 +/- 0.2 x 10(6) microm3), and proteinuria (171 +/- 21 mg/day) even
      further. Our data show that the lack of E2 and presence of androgens contribute
      to progressive renal disease induced by RW hypertension, suggesting that gonadal
      steroid status is an independent factor in the greater susceptibility men exhibit
      toward hypertension-associated renal disease compared with women.

PMID- 15572526
TI  - Peripheral lung remodelling in asthma and chronic obstructive pulmonary disease.

PMID- 15572527
TI  - Controversial topics in tuberculosis.

PMID- 15572528
TI  - Antibiotics in exacerbations of COPD: lessons from the past.

PMID- 15572529
TI  - Lung cancer: clinical presentation and specialist referral time.
AB  - Many textbooks describe symptoms and signs of lung cancer but refer to old series
      of patients. To update knowledge about lung cancer presentation, a study was
      carried out on 1,277 consecutive lung cancer patients, who were seen in a single
      Institution from January 1989 to October 2002. A set of 33 anthropometric,
      clinical, physical, laboratory, radiological, pathological and follow-up
      variables was prospectively recorded for all patients. In addition, information
      was obtained concerning symptoms of alarm (i.e. potential concern), times to
      specialist referral and the mix of symptoms at presentation. Patients were
      carefully followed-up and their subsequent clinical course was recorded. Casual
      discovery with absence of symptoms occurred more frequently towards the end of
      the study period and the prevalence of chest pain became less common. No other
      time-dependent changes were found in the presenting symptoms. Delay in specialist
      referral was longer when presentation was provoked by cough or by the occurrence
      of systemic symptoms, such as weight loss, anorexia and asthenia. Referral delay
      was longer towards the end of the study, perhaps related to an increase in the
      number of elderly patients with co-morbidities. Both alarm and prevalence
      symptoms were strong predictors of the clinical outcome, as found in both
      univariate analysis (favourable: casual discovery and chest infection;
      unfavourable: chest pain, dyspnoea, systemic symptoms and symptoms of local or
      systemic dissemination) and in multivariate analysis (favourable: chest
      infection). Early presentation of lung cancer is characterised by a specific
      symptomatic pattern. Knowledge of this pattern may help to improve the rate of
      early diagnosis.

PMID- 15572530
TI  - Value of imprint cytology for ultrasound-guided transthoracic core biopsy.
AB  - The aim of this study was to investigate the possible additional diagnostic
      information provided by imprint cytology when performing ultrasound-guided
      transthoracic core biopsy and to evaluate whether it could optimise the biopsy
      procedure. A total of 155 transthoracic core biopsies with touch imprint smears
      were performed under ultrasound guidance, with 127 malignant and 28 benign
      lesions. The imprint smears were stained using Riu's method and interpreted by a
      cytopathologist. These were compared with the histopathology of core biopsy
      specimens and the final diagnosis of malignant versus benign disease. The overall
      diagnostic accuracy of imprint cytology was 94% (146 out of 155).
      Histopathological analysis showed an overall accuracy of 94% (146 out of 155),
      with a sensitivity of 94% (119 out of 127) and negative predictive value of 79%
      (27 out of 34). The combination of these two methodologies had an increased
      overall accuracy and negative predictive value of 98% (152 out of 155) and 90%
      (28 out of 31), respectively. The results of imprint cytology and histopathology
      were in agreement in 143 patients (92%). In conclusion, imprint cytology of
      ultrasound-guided transthoracic core biopsy is a sensitive procedure for
      diagnosing peripheral thoracic lesions, and it may increase the diagnostic
      accuracy and cancer negative prediction of biopsy alone. With an on-site
      approach, imprint cytology may help to assess the adequacy of biopsy specimens
      and optimise the biopsy procedure.

PMID- 15572531
TI  - Airway remodelling assessed by sputum and high-resolution computed tomography in
      asthma and COPD.
AB  - It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue
      inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the
      airways, as assessed by high-resolution computed tomography (HRCT) scan. The
      relationships between these markers and the magnitude of structural changes of
      the airways in asthma and chronic obstructive pulmonary disease (COPD) were
      assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild
      and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan
      abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan
      abnormalities correlated with the degree of airway obstruction in COPD and in
      severe asthma. HRCT scan abnormalities also correlated with the levels of sputum
      elastase both in COPD and in severe asthma. HRCT scan abnormalities were
      associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD.
      In conclusion, this study demonstrates that sputum elastase and the
      metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated
      with the magnitude of high-resolution computed tomography scan abnormalities of
      the airways in asthma and chronic obstructive pulmonary disease, and suggests
      that the levels of these markers reflect the extent of structural changes of the
      airways.

PMID- 15572532
TI  - Thrombin induces collagen gel contraction partially through PAR1 activation and
      PKC-epsilon.
AB  - The ability of fibroblasts to contract three-dimensional collagen gels has been
      used as an in vitro model of the tissue contraction which characterises both
      normal repair and fibrosis. Among its actions, thrombin can activate the protease
      activated receptor (PAR)1 and, thereby, stimulate inflammation and repair. The
      current study evaluated whether thrombin could stimulate fibroblast-mediated
      collagen gel contraction by activating PAR1 and whether its downstream signalling
      depends on protein kinase C (PKC)-epsilon. Human foetal lung fibroblasts (HFL-1)
      were cultured in three-dimensional collagen gels and the area of the gels was
      measured by image analyser. Both thrombin and TFLLR, a selective PAR1 agonist,
      stimulated collagen gel contraction mediated by HFL-1. After RNA interference
      mediated PAR1 knockdown in HFL-1, both thrombin and the PAR1 agonist-induced gel
      contraction were partially inhibited (by 22.4+/-2.2% and 17.6+/-5.6%,
      respectively). The gel contraction stimulated by thrombin was also reduced by a
      nonspecific PKC inhibitor and a calcium-independent PKC-epsilon inhibitor. Both
      thrombin and TFLLR significantly increased PKC-epsilon activity, and this effect
      was blocked by PAR1 knockdown. Thrombin stimulates collagen gel contraction at
      least partially through activation of protease-activated receptor 1 and protein
      kinase C-epsilon, and may contribute to tissue remodelling in inflammatory airway
      and lung diseases.

PMID- 15572533
TI  - Influenza vaccination in asthmatic children: effects on quality of life and
      symptoms.
AB  - This study aimed to detect the effect of influenza vaccination on quality of
      life, symptomatology and spirometry in asthmatic children. A randomised double
      blind placebo-controlled trial in 696 (296 in 1999-2000 and 400 in 2000-2001)
      asthmatic children aged 6-18 yrs, which were vaccinated with either vaccine or
      placebo, was performed. Children participated for only one influenza season. They
      recorded symptoms in a diary and reported when symptom scores reached a
      predefined severity level. If this occurred research nurses visited them twice,
      first to take a pharyngeal swab and spirometry, and a week later to assess
      quality of life over the past illness week. Compared with placebo, vaccination
      improved health-related quality of life in the weeks of illness related to
      influenza-positive swabs. However, no effect was found for respiratory symptoms
      recorded in the diaries during those weeks. Similarly, no differences were found
      for quality of life in all weeks of illness or for respiratory symptoms
      throughout the seasons. Influenza vaccination was found to have a moderately
      beneficial effect on quality of life in influenza-positive weeks of illness in
      children with asthma.

PMID- 15572534
TI  - Treatment of exercise-induced asthma with beclomethasone dipropionate in children
      with asthma.
AB  - A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly
      increases drug delivery to the airways. Therefore, even low doses of HFA-BDP
      should be effective, and the present study assesses this. A randomised, double
      blind, crossover study was used to compare the effect of placebo, HFA-BDP 50
      microg or 100 microg given q.d. (QVAR(TM) Autohaler(TM); 3M Pharmaceuticals, St.
      Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide
      (eNO). After a 14-day run-in, 25 children (5-14 yrs old) entered three 4-week
      treatment periods, separated by a 1-week washout. After each period, the fall in
      forced expiratory volume in one second (FEV1), after an exercise test, and eNO
      were measured. Significant treatment effects with no carry-over or period effects
      were seen for both eNO and maximum fall in FEV1 after exercise. Differences were
      seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and
      either dose of HFA-BDP, but not between the two active doses (50 microg: fall in
      FEV1=20.8%, eNO=9.3 ppb; 100 microg: fall in FEV1=20.9%, eNO=8.9 ppb). In
      conclusion, low q.d. doses of hydrofluoroalkane-beclomethasone dipropionate
      reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further
      studies are needed to assess whether q.d. administration of beclomethasone
      dipropionate is as effective as b.i.d. administration.

PMID- 15572535
TI  - Ecological associations between asthma prevalence and potential exposure to
      farming.
AB  - Farming and exposure to livestock have been proposed as protective against the
      development of asthma in children. An ecological study was conducted to examine
      the support for these relationships in the USA. County-specific aggregate
      measures were used to examine the relationship between the prevalence of asthma
      and wheeze in 7th and 8th grade school children (aged 12-14 yrs) and selected
      measures of potential exposure to farming in the state of North Carolina.
      Binomial regression models were fitted to quantify these relationships, with
      adjustments for parental smoking, socioeconomic status, sex and race. Regression
      coefficients were reported for an increment of one interquartile range (IQR) in
      each indicator of exposure. The prevalence of asthma showed decreasing trends for
      most indicators of farm exposure. Regression results suggested that the largest
      decreases in asthma prevalence were associated with the number of farms (-5.0%
      per IQR increment), acreage of hay (-7.2% per IQR increment) and beef cattle (
      7.8% per IQR increment). The pattern of results was similar for wheezing. In
      conclusion, the findings of this study are consistent with the hypothesis that
      certain farm exposures are protective against childhood asthma. Further research
      with individual-level data is needed to identify the specific protective
      exposures.

PMID- 15572536
TI  - A prospective study of asthma incidence and its predictors: the RHINE study.
AB  - The objective of this longitudinal study was to estimate the incidence rate of
      asthma, and to compare the incidence between subjects with or without baseline
      reporting of certain respiratory symptoms. A follow-up of the random population
      samples in the European Respiratory Health Survey (ECRHS) in Sweden, Norway,
      Denmark, Iceland and Estonia was conducted in 1999-2001, in a population aged 30
      54 yrs at follow-up (n=14,731). Asthma was defined as reporting either asthma or
      physician-diagnosed asthma, and a reported year when asthma symptoms were first
      noticed. Incidence rates, incidence rate ratios and hazard ratios were calculated
      with 95% confidence intervals. The incidence rate of asthma was 2.2 cases per
      1,000 person-yrs. The incidence was higher among females (2.9 cases.1,000 person
      yrs(-1)) than among males (1.5 cases.1,000 person-yrs(-1)). When subjects with
      baseline reporting of wheezing were excluded, the incidence rate decreased to 1.7
      cases.1,000 person-yrs(-1), with a further decrease to 1.5 cases.1,000 person
      yrs(-1) after exclusion of subjects with wheezing, nocturnal dyspnoea, chest
      tightness and cough. There was a strong association between onset of asthma and
      wheezing at baseline. In this prospective, population-based study, the incidence
      rate of asthma in the whole population sample ranged 1.5-2.2.1,000 person-yrs(
      1), with a higher incidence range among females. The incidence was dependent on
      the extent to which subjects with respiratory symptoms were excluded from follow
      up. Hence, for comparability between studies, the exclusion criteria in the
      follow-up population must be stated.

PMID- 15572537
TI  - Levofloxacin versus clarithromycin in COPD exacerbation: focus on exacerbation
      free interval.
AB  - Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary
      disease (COPD) shows some immediate clinical benefits and may also minimise the
      frequency of further recurrences. Patients (n=511) were enrolled into a
      randomised double-blind multicentric study comparing the exacerbation-free
      interval (EFI), efficacy and safety of 7-day levofloxacin versus 10-day
      clarithromycin in patients with COPD exacerbation. Patients were monitored over a
      1-yr period. A total of 434 patients (per protocol population) received the
      medication for > or =5 days. The median EFI in the per protocol population was
      300 days for levofloxacin and 350 days for clarithromycin. For patients with a
      new documented exacerbation during follow-up (n=223), the median EFI was 100.5
      days in the levofloxacin group and 95 days for clarithromycin. No significant
      differences in EFI between groups could be observed when stratifying the study
      population according to microbial aetiology and severity of bronchial
      obstruction. Levofloxacin and clarithromycin showed similar clinical success
      rates. The bacteriological success rate was significantly higher in the
      levofloxacin group. Both antibiotics were well tolerated. In summary,
      levofloxacin was associated with a significantly higher bacteriological
      eradication rate but similar exacerbation-free interval in patients with chronic
      obstructive pulmonary disease exacerbation compared to clarithromycin.

PMID- 15572538
TI  - Assessments for oxygen therapy in COPD: are we under correcting arterial oxygen
      tensions?
AB  - There is little data about the use of different oxygen sources during assessment
      for long-term oxygen therapy (LTOT) and how this impacts upon blood oxygen
      tensions and prescribed flow rates. Patients with chronic obstructive pulmonary
      disease (COPD), n=30, had assessments for LTOT using both an oxygen-concentrator
      and piped hospital oxygen (wall-oxygen) as supply sources. In addition, a random
      survey of 64 hospitals was conducted to determine what source of oxygen supply
      was used during assessments. Wall-oxygen was used by 89% of hospitals to perform
      assessments. During assessments, the median oxygen flow required to achieve an
      arterial oxygen tension (Pa,O2) >8 kPa was significantly greater for an oxygen
      concentrator than for wall-oxygen, with a median difference (range) in flow of 1
      (0-3) L. This difference was most likely in those with an forced expiratory
      volume <30% of predicted. At an oxygen flow of 1 L.min(-1), the mean P(a,O2)
      using an oxygen-concentrator was significantly lower than that of the wall-oxygen
      value, with a difference of 1.32+/-1.19 kPa (mean+/-SD). The common practice of
      using wall-oxygen to perform assessments significantly underestimates the
      required oxygen-concentrator flow rate. This may have implications for the long
      term effect of domiciliary oxygen therapy.

PMID- 15572539
TI  - Vasoactive intestinal peptide receptors in the airways of smokers with chronic
      bronchitis.
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide involved in the regulation
      of airway mucus secretion. The biological functions of VIP are mediated through
      two receptors, the vasoactive intestinal peptide receptor type 1 (VPAC1R) and
      type 2 (VPAC2R). The aim of this study was to quantify the expression of both
      VPAC1R and VPAC2R in the central airways of smokers with chronic bronchitis.
      Surgical specimens were obtained from 33 smokers undergoing thoracotomy for
      localised pulmonary lesions: 23 smokers with symptoms of chronic bronchitis and
      10 asymptomatic smokers with normal lung function. By using immunohistochemical
      and microscopic analysis, an increased expression of VPAC1R, but not VPAC2R, was
      found in bronchial epithelium, bronchial glands and vessels of smokers with
      symptoms of chronic bronchitis compared with asymptomatic smokers. Smokers with
      symptoms of chronic bronchitis also had an increased number of mononuclear cells
      positive for both VPAC1R and VPAC2R in the bronchial submucosa. In conclusion,
      the expression of type 1 and type 2 vasoactive intestinal peptide receptors is
      increased in the central airways of smokers with chronic bronchitis, suggesting
      their possible involvement in the pathogenesis of chronic bronchitis.

PMID- 15572540
TI  - Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage
      fluid.
AB  - Surfactant protein (SP)-A and SP-D are collagen-like glycoproteins that are
      synthesised in the distal pulmonary epithelium. This study examined the effects
      of ageing and long-term smoking on SP-A and SP-D in the lungs. The possible links
      to the development of pulmonary emphysema were also investigated. Sequential
      lavage was performed in young and middle-aged or elderly nonsmokers and
      asymptomatic current smokers with various smoking histories. Middle-aged or
      elderly smokers were further categorised according to the presence of emphysema
      by high-resolution computed tomography. Levels of SP-A and SP-D in bronchial
      lavage (BL) fluid and in bronchoalveolar lavage (BAL) fluid were quantified by
      ELISA. Significant decreases in SP-A were seen with age in nonsmokers in BL
      fluid, but not in BAL fluid. Middle-aged or elderly smokers with emphysema had
      lower levels of SP-A in both BL and BAL fluids when compared with young subjects,
      and in BL fluid when compared with middle-aged or elderly smokers without
      emphysema. SP-D did not change with age alone, however, it was decreased in
      middle-aged or elderly smokers when compared with similarly aged nonsmokers. In
      conclusion, surfactant protein-A may decrease with age alone or due to the
      cumulative effects of long-term smoking and development of emphysema, while
      surfactant protein-D decreases due to long-term smoking.

PMID- 15572541
TI  - Adaptation of the diaphragm and the vastus lateralis in mild-to-moderate COPD.
AB  - The chronology of diaphragm and vastus lateralis adaptation in chronic
      obstructive pulmonary disease (COPD) has not been studied. The hypothesis of this
      study was that muscle changes would occur earlier in the diaphragm than in the
      vastus lateralis in COPD, a finding that would suggest that local factors would
      be more important than systemic factors in determining the muscle phenotypic
      expression, at least in mild-to-moderate disease. The adaptation of the vastus
      lateralis and diaphragm muscles was evaluated in patients with mild-to-moderate
      COPD and in subjects with normal pulmonary function. In both groups, the
      oxidative potential and the number of lipofuscin inclusions were higher in the
      diaphragm than in the vastus lateralis. Compared to control, the diaphragm in
      COPD had a higher oxidative capacity and a higher proportion of type I fibres,
      with a reciprocal decrease in type IIA fibres, while there was no difference in
      diaphragmatic cross sectional areas, capillarisation and lipofuscin inclusions.
      No significant differences were found in the vastus lateralis from both groups.
      In conclusion, these data indicate that the diaphragm in controls and in chronic
      obstructive pulmonary disease has a higher oxidative potential than the vastus
      lateralis, and that muscle adaptation occurs earlier in the diaphragm than in the
      vastus lateralis in mild-to-moderate chronic obstructive pulmonary disease.

PMID- 15572542
TI  - Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR
      spectroscopy study.
AB  - Patients with obstructive sleep apnoea syndrome frequently have cognitive
      deficits, especially related to executive functions, which cannot be fully
      explained by daytime sleepiness and are partial irreversible after nasal
      continuous positive airway pressure treatment. The causal mechanism of these
      cognitive deficits is not yet known, but it has been proposed that they are
      associated with chemical and structural brain cell injury. The aim of this study
      was to investigate brain metabolism in patients with sleep apnoea syndrome.
      Twenty-two patients with severe sleep apnoea and 10 healthy volunteers of
      comparable age were studied using single voxel proton magnetic resonance
      spectroscopy. Magnetic resonance spectra were obtained from prefrontal cortex,
      parieto-occipital and frontal periventricular white matter. N-acetylaspartate-to
      creatine and choline-to-creatine ratios were significantly lower in the frontal
      white matter of obstructive sleep apnoea patients when compared to controls.
      Absolute concentrations of N-acetylaspartate and choline were also significantly
      reduced in the frontal white matter of patients with sleep apnoea. Frontal lobe
      white matter lesions are known to be associated with cognitive executive
      dysfunction. The findings of this study may offer an explanation for the
      sometimes irreversible cognitive deficits associated with sleep apnoea.

PMID- 15572543
TI  - Night-to-night variation of the oxygen desaturation index in sleep apnoea
      syndrome.
AB  - The current study investigated the night-to-night variability and diagnostic
      accuracy of the oxygen desaturation index (ODI), as measured by ambulatory
      monitoring, in the diagnosis of mild and moderate obstructive sleep apnoea
      hypopnoea syndrome. To assess the variability of the ODI, 35 patients were
      monitored at home during 7 consecutive nights by means of a portable recording
      device, the MESAM-IV. The ODI variability factor and the influence of age, body
      mass index (BMI), alcohol, and body position were assessed. Furthermore, the
      diagnostic accuracy of the MESAM-IV was measured by comparison with
      polysomnographical outcomes in 18 patients. During home recording, the median ODI
      was 10.9 (interquartile range: 5.8-16.1) across the patients. Although the
      reliability of the ODI was adequate, the probability of placing the patient in
      the wrong severity category (ODI < or =15 or ODI >15) when only one single
      recording was taken is 14.4%. ODI variability was not significantly influenced by
      age, BMI, time spent in a supine position, or mild dosages of alcohol. A good
      correlation was found between the apnoea-hypopnoea index and the ODI. In
      conclusion, the findings suggest that the diagnostic accuracy of the MESAM-IV is
      strong, since the oxygen desaturation index is correlated with the apnoea
      hypopnoea index. In most obstructive sleep apnoea-hypopnoea syndrome patients,
      oxygen desaturation index variability is rather small, and screening could be
      reliably based on single 1-night recordings.

PMID- 15572544
TI  - Alveolar antioxidant status in patients with acute respiratory distress syndrome.
AB  - In the acutely inflamed lung, oxidant stress occurs within the alveolar
      compartment. Under these conditions, the regulation of low molecular weight
      antioxidants in the epithelial lining fluid is poorly understood. Therefore,
      antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of
      patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy
      volunteers (n=20). Reduced glutathione (GSH), oxidised glutathione (GSSG;
      enzymatic assay), retinol (vitamin A), alpha-tocopherol (vitamin E), ascorbic
      acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl
      phospholipids), polyunsaturated fatty acids (PUFA; both by gas-liquid
      chromatography), and F2-isoprostanes (ELISA) were quantified. All values are
      expressed as concentrations in cell-depleted BALF. GSSG (ARDS: 0.13+/-0.02
      microM; control: 0.03+/-0.01 microM; mean+/-sem) and F2-isoprostanes (ARDS: 78+/
      10 pM; control: 26+/-5 pM) were increased in ARDS, thus indicating oxidant
      stress. GSH levels in patients did not change significantly, whereas
      concentrations of vitamins A and C, vitamin E (ARDS: 77+/-15 nM; control: 26+/-3
      nM) and uric acid (ARDS: 11.8+/-2.2 microM; control: 0.7+/-0.0 microM) were
      significantly elevated in ARDS. PUFA of total lipids, which may act as
      sacrificial antioxidants, increased by a factor of approximately 3 in patients,
      but plasmalogens showed a significant decrease. In conclusion, low molecular
      weight antioxidants are elevated in the alveolar compartment of patients with
      acute respiratory distress syndrome. Further research is warranted to elucidate
      the molecular mechanisms underlying this finding.

PMID- 15572545
TI  - Predictive value of BAL cell differentials in the diagnosis of interstitial lung
      diseases.
AB  - The current authors aimed to quantify how the likelihood for a given diagnosis
      changes with the knowledge of bronchoalveolar lavage (BAL) cell differentials. As
      an initial estimate (a priori probability), frequencies of final diagnoses were
      taken. Using categorisations for cell differentials, a posteriori probabilities
      were then derived for each disease, according to Bayes. The analysis was
      performed in three of five groups of diagnoses suspected prior to BAL:
      interstitial lung disease (ILD; n=710), inflammatory disease (n=583), or lung
      tumour mimicking ILD (n=455). Overall, out of 1,971 patients, 18.3% had
      sarcoidosis, 7.7% usual interstitial pneumonia (UIP), 4.4% extrinsic allergic
      alveolitis (EAA), and 19.0% tumours. In the group with suspected ILD, the
      likelihood for sarcoidosis increased from 33.7 to 68.1% when lymphocyte numbers
      were 30-50% and granulocyte numbers were low; the likelihood for UIP increased
      from 15.8 to 33.3% when lymphocyte numbers were <30% with granulocytes elevated.
      CD4/CD8 was informative, especially in sarcoidosis and EAA. Despite considerable
      increases, the likelihood of rare diseases rarely reached appreciable values.
      Similar results were obtained in the other two groups of suspected diagnoses. In
      conclusion, these data suggest that bronchoalveolar lavage cell counts per se
      provide substantial diagnostic information only in relatively frequent diseases,
      such as sarcoidosis and usual interstitial pneumonia, and are less helpful in
      infrequent diseases.

PMID- 15572546
TI  - Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial
      hypertension.
AB  - It has been proposed that targeted treatments should be combined for patients
      with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently
      to monotherapy. This study followed the clinical course of nine patients with
      severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient
      clinical improvement, eventually followed by a decline in exercise tolerance, who
      received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil.
      Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise
      testing (CPET). The 6MWD at baseline was 346+/-66 m and improved to 403+/-80 m 3
      months after introduction of bosentan treatment. However, this effect was not
      sustained and, after an interval of 11+/-5 months, the walk distance had declined
      to 277+/-80 m. At this point, sildenafil was added to bosentan. Three months
      later, the 6MWD had increased to 392+/-61 m and the patients remained stable
      throughout the median follow-up of 9 months (range 6-12). Measurement of the
      maximum oxygen uptake during CPET confirmed these results. The combination of
      bosentan and sildenafil was well tolerated by all patients. These preliminary
      data suggest that combining bosentan and sildenafil may be safe and effective in
      patients with idiopathic pulmonary arterial hypertension.

PMID- 15572547
TI  - Comparison between exhaled and sputum oxidative stress biomarkers in chronic
      airway inflammation.
AB  - The aim of the present study was to compare aldehyde levels resulting from lipid
      peroxidation in exhaled breath condensate (EBC) and induced sputum (IS)
      supernatant of subjects with asthma and chronic obstructive pulmonary disease
      (COPD). Aldehydes (malondialdehyde (MDA), acrolein, n-hexanal (C6), n-heptanal
      (C7), n-nonanal (C9), 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE)) in both
      biological fluids were measured by liquid chromatography-tandem mass
      spectrometry. MDA concentrations in sputum were 132.5 nM (82.5-268.8) and 23.7 nM
      (9-53.7) in EBC. Similarly, C6, C7 and C9 concentrations in IS were 1.5-4.7-fold
      higher than in EBC. Acrolein levels were 131.1 nM (55.6-264.6) in IS and 45.3 nM
      (14.4-127.1) in EBC. The concentrations of HNE and HHE in IS were not
      significantly different from the levels in EBC. Aldehyde levels in EBC did not
      show any correlation with aldehyde levels in IS or with differential sputum
      cellular count. In COPD, MDA in EBC, but not its IS counterpart, was negatively
      correlated with the severity of disease. In conclusion, the data presented here
      show that aldehydes can be detected in both exhaled breath condensate and
      supernatant of induced sputum, but that their relative concentrations are
      different and not correlated with each other. Therefore, with regard to lipid
      peroxidation products, exhaled breath condensate and induced sputum must be
      considered as independent techniques.

PMID- 15572548
TI  - Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic
      subjects.
AB  - The aim of this study was to assess whether hyperosmolarity affects granulocyte
      mediator levels in induced sputum of asthmatic subjects. A total of 32 mild-to
      moderate asthmatics, who inhaled either hypertonic (HS; 4.5% NaCl) or isotonic
      (IS; 0.9% NaCl) solutions for 15 min, were studied. Selected sputum was used for
      analysis. Eosinophil cationic protein (ECP), eosinophil protein X (EPX),
      myeloperoxidase (MPO) and free neutrophil elastase (NE) were measured in sputum
      supernatant. Sample weight, total and differential cell counts, as well as
      viability and squamous cell percentage were no different after the two tests. No
      significant differences in ECP, EPX, MPO or NE levels were observed between HS-
      and IS-induced sputum. Repeatability of the two tests was good for macrophages,
      neutrophils, eosinophils, ECP, EPX and NE, but not for lymphocytes and MPO. In
      conclusion, hyperosmolarity does not affect sputum cell counts and the levels of
      most granulocyte degranulation markers examined in this study, confirming that
      both hypertonic and isotonic solutions can be reliably used to induce sputum in
      asthmatics.

PMID- 15572549
TI  - Diagnosis and pharmacotherapy of severe acute respiratory syndrome: what have we
      learnt?
AB  - In 2003, the onset of severe acute respiratory syndrome (SARS) caused worldwide
      chaos. Although SARS was eradicated by isolation towards the end of 2003,
      sporadic cases have been reported in Singapore, Taiwan and mainland China. In
      this review, SARS is discussed as a disease, as well as its diagnosis, management
      and pharmacotherapy. Respiratory physicians and healthcare professionals have to
      be aware of advances in the understanding of the diagnosis and management of
      severe acute respiratory syndrome. More research is required in order to prepare
      for if this respiratory infection recurs, but there are concerns that adequate
      pharmaceutical support may be lacking for the development of a vaccine.

PMID- 15572550
TI  - The immune response to resistive breathing.
AB  - Resistive breathing is an "immune challenge" for the body, initiating an
      inflammatory response consisting of an elevation of plasma cytokines, and the
      recruitment and activation of lymphocyte subpopulations. These cytokines do not
      originate from monocytes, but are, instead, produced within the diaphragm,
      secondary to the increased muscle activation. Oxidative stress is a major
      stimulus for the cytokine induction, secondary to resistive breathing. The
      production of cytokines within the diaphragm may be mediating the diaphragm
      muscle fibre injury that occurs with strenuous contractions, or contributing
      towards the expected repair process. These cytokines may also compromise
      diaphragmatic contractility or contribute towards the development of muscle
      cachexia. They may also have systemic effects, mobilising glucose from the liver
      and free fatty acid from the adipose tissue to the strenuously working
      respiratory muscles. At the same time, they stimulate the hypothalamic-pituitary
      adrenal axis, leading to production of adrenocorticotropin and beta-endorphins.
      The adrenocorticotropin response may represent an attempt of the organism to
      reduce the injury occurring in the respiratory muscles via the production of
      glucocorticoids and the induction of the acute phase-response proteins. The beta
      endorphin response would decrease the activation of the respiratory muscles and
      change the pattern of breathing, which becomes more rapid and shallow, possibly
      in an attempt to reduce and/or prevent further injury to the respiratory muscles.

PMID- 15572551
TI  - On the nature of Mycobacterium tuberculosis-latent bacilli.
AB  - Mycobacterium tuberculosis-latent bacilli are microorganisms that adapt to
      stressful conditions generated by the infected host against them. By slowing
      metabolism or becoming dormant, they may counterbalance these conditions and
      appear as silent to the immune system. Moreover, the dynamic turnover of the
      infected cells provokes a constant reactivation of the latent bacilli when the
      environmental conditions are favourable, or an activation after being dormant in
      necrotic and fibrotic lesions for a long period of time. Since there is no in
      vivo nor in vitro evidence for quick resuscitation of dormant bacilli, the
      current authors strongly favour the possibility that latent tuberculosis
      infection can be maintained for no longer than approximately 10 yrs, which is,
      nowadays, a time period very close to that considered for "primary" tuberculosis.
      This concept may also be helpful for newer epidemiological considerations
      regarding the real impact of reinfection in tuberculosis.

PMID- 15572552
TI  - Noninvasive monitoring of respiratory mechanics during sleep.
AB  - The sleep apnoea-hypopnoea syndrome is characterised by recurrent obstructions of
      the upper airway, resulting in sleep disruption and arterial oxygen
      desaturations. Noninvasive assessment of respiratory mechanics during sleep is
      helpful in facilitating the diagnosis and treatment of patients with sleep apnoea
      hypopnoea syndrome. This series summarises the different tools that are currently
      available to noninvasively assess respiratory mechanics during sleep breathing
      disturbances. These techniques are classified according to the main variable
      monitored: ventilation, breathing effort or airway obstruction. Changes in
      patient ventilation are assessed by recording flow or volume signals by means of
      pneumotachographs, thermistors or thermocouples, nasal prongs or thoraco
      abdominal bands. Common tools to noninvasively assess breathing efforts are the
      thoraco-abdominal bands and the pulse transit time technique. Upper airway
      obstruction is noninvasively characterised by its upstream resistance and its
      critical pressure or by means of the forced oscillation technique. Given the
      technical and practical limitations of each technique, combining different tools
      improves the reliability and robustness of patient assessment during sleep.

PMID- 15572553
TI  - Relapse of respiratory insufficiency one year after organising pneumonia.

PMID- 15572554
TI  - A painful and swollen right breast in a young male.

PMID- 15572555
TI  - Radicals in the church.

PMID- 15572556
TI  - Combination therapy with maintenance budesonide and formoterol in COPD.

PMID- 15572557
TI  - Progressive damage on high-resolution computed tomography.

PMID- 15572558
TI  - Variable phenotype associated with SP-C gene mutations: fatal case with the I73T
      mutation.

PMID- 15572561
TI  - Racism: a mental illness?

PMID- 15572562
TI  - Datapoints: Costs associated with the treatment of patients with bipolar disorder
      in a managed care organization.

PMID- 15572563
TI  - Economic grand rounds: systemwide costs associated with second-generation
      antipsychotics in the treatment of schizophrenia.

PMID- 15572564
TI  - Unemployment, job retention, and productivity loss among employees with
      depression.
AB  - OBJECTIVE: This study comprehensively assessed the work outcomes of employees
      with depression. METHODS: We collected baseline and six-month follow-up survey
      data from 229 employees with depression and two employee comparison groups: a
      group of healthy patients for the control group (N=173) and a group with
      rheumatoid arthritis (N=87), a frequent source of work disability. Outcomes
      included new unemployment and, within the employed subgroup, job retention
      (versus job turnover), presenteeism (that is, diminished on-the-job performance
      and productivity), and absenteeism. RESULTS: At the six-month follow-up, persons
      with depression had more new unemployment--14 percent for persons in the
      dysthymia group, 12 percent for persons in the major depression group, and 15
      percent for persons in the group with both dysthymia and major depression,
      compared with 2 percent for persons in the control group and 3 percent for
      persons in the rheumatoid arthritis group. Among participants who were still
      employed, those with depression had significantly more job turnover,
      presenteeism, and absenteeism. CONCLUSIONS: In addition to helping employees with
      depression obtain high-quality depression treatment, new interventions may be
      needed to help them to overcome the substantial job upheaval that this population
      experiences.

PMID- 15572565
TI  - Disparities in the adequacy of depression treatment in the United States.
AB  - OBJECTIVE: There is evidence of disparities in depression treatment by factors
      such as age, race or ethnicity, and type of insurance. The purpose of this study
      was to assess whether observed disparities in treatment are due to differences in
      rates of treatment initiation or to differences in the quality of treatment once
      treatment has been initiated. METHODS: Logistic regression models using data from
      the 2000 Medical Expenditure Panel Survey were estimated to assess the role of
      age, race or ethnicity, and type of insurance on rates of initiation of
      depression treatment for persons with self-reported depression and on rates of
      adequate treatment for those receiving treatment. RESULTS: African Americans and
      Latinos were significantly less likely to fill an antidepressant prescription
      than Caucasians. However, among patients who filled at least one prescription for
      an antidepressant, there were no racial or ethnic disparities in the probability
      of receiving an adequate trial of antidepressant medication. African Americans
      were more likely than Latinos and Caucasians to receive an adequate course of
      psychotherapy. Persons who did not have insurance coverage were less likely to
      initiate any depression treatment compared with those who did have insurance.
      However, if treatment was initiated, no difference in the probability of
      receiving adequate treatment was observed. Elderly persons were less likely to
      receive an adequate course of psychotherapy or counseling compared with younger
      persons. CONCLUSIONS: Disparities in depression treatment appear to be due mainly
      to differences in rates of initiation of depression treatment, given that rates
      of adequate care generally did not differ once treatment was initiated.

PMID- 15572566
TI  - Comparing the quality of antidepressant pharmacotherapy in the Department of
      Veterans Affairs and the private sector.
AB  - OBJECTIVE: Comparing quality of care between large health care systems is
      important for health systems management. This study compared measures of the
      quality of pharmacotherapy for patients with major depression across a sample of
      patients from the Department of Veterans Affairs (VA) and the private sector.
      METHODS: In this observational study, all patients who were given a new
      prescription for an antidepressant and a diagnosis of major depression in the VA
      during fiscal year 2000 were identified by using administrative data (N=27,713).
      In the private sector, a similar sample of patients were identified by using
      Medstat's MarketScan database (N=4,852). For both groups, measures of the quality
      of antidepressant pharmacotherapy were constructed. These measures were compared
      across the two groups by using logistic regression models. Controls for age,
      gender, comorbid disorders, and initial antidepressant drug prescribed were
      included in some models. RESULTS: Although the populations had different
      demographic and clinical characteristics, differences in the quality measures
      between the two systems were few, with the VA slightly outperforming the private
      sector in the prescription of antidepressants during the acute phase of
      treatment, the first 84 days (84.7 compared with 81 percent) and during the
      maintenance phase of treatment, the first 181 days (53.9 compared with 50.9
      percent). Patient characteristics that were associated with quality measures
      included being older, being female, and having a comorbid diagnosis of substance
      use disorder, bipolar disorder, or anxiety or adjustment disorder. CONCLUSIONS:
      Both systems had relatively high rates of adherence to pharmacotherapy
      guidelines. Even though the populations in the two systems were different,
      adjusting the analyses for clinical characteristics did little to change the
      measured differences between the two systems.

PMID- 15572567
TI  - Use of medical and behavioral health services by adolescents with bipolar
      disorder.
AB  - OBJECTIVE: This study compared use of medical and behavioral health care by
      adolescents with bipolar disorder and other adolescents and identified areas in
      need of more clinical attention. METHODS: Medical and behavioral health insurance
      claims from 1996 for 100,880 adolescents were examined and categorized.
      Differences between and among various categories of disease were explored by
      using multivariate analyses. RESULTS: Among the 10,970 adolescents who used at
      least one behavioral health service, adolescents with bipolar disorder (N=326)
      had significantly higher behavioral health costs than those with mood or non-mood
      disorders, a result driven by these adolescents' significantly higher hospital
      admission rates for behavioral health care. Adolescents with bipolar disorder
      also had significantly higher medical admission rates compared with adolescents
      who had other behavioral health diagnoses. More than half of the 14 medical
      admissions for adolescents with bipolar disorder were due to drug overdose.
      CONCLUSIONS: Reallocation of medical and behavioral health resources to improve
      ambulatory treatment of bipolar disorder among adolescents has the potential to
      decrease the use and costs of health care while improving the welfare of these
      adolescents and their families.

PMID- 15572568
TI  - A review of mood disorders among juvenile offenders.
AB  - OBJECTIVES: This article provides an overview of what is known about the
      prevalence, diagnosis, and effective treatment of mood disorders among youths,
      particularly among juvenile offenders, and discusses the unique problems that
      arise for the delivery of treatment services. The relationship between mood
      disorders and disruptive or delinquent behaviors as well as the particular
      importance of proper diagnosis and treatment of mood disorders in this population
      are discussed. METHODS: A search was conducted of the MEDLINE and PsycINFO
      databases for articles that had been published since 1980 on mood disorders in
      the juvenile offender population as well as articles on adolescent mood
      disorders. RESULTS: The studies on the prevalence of mood disorders among
      juvenile offenders varied significantly in the methodology used and in the rates
      of prevalence found, although all studies showed that this population had high
      rates of mood disorders. The identification and effective treatment of mood
      disorders is critical because these disorders are a leading cause of suicide
      among adolescents and because mood disorders may contribute to or exacerbate
      delinquent and disruptive behaviors. CONCLUSIONS: Juvenile detainees have a
      constitutional right to needed mental health treatment. More comprehensive mental
      health services are required to ensure that juvenile offenders with mental
      illness are identified and cared for appropriately. Doing so not only will
      alleviate painful symptoms but may also contribute significantly to improvements
      in psychosocial functioning, interpersonal relations, and school performance and
      to decreases in delinquent, disruptive, and suicidal behaviors.

PMID- 15572569
TI  - Depression, anxiety, and physical impairments and quality of life in the U.S.
      noninstitutionalized population.
AB  - OBJECTIVE: The objective of this study was to examine health-related quality of
      life and health behaviors among persons reporting a primary mental health
      impairment compared with those reporting a primary physical health impairment and
      those reporting no impairment. METHODS: Data were obtained from the Behavioral
      Risk Factor Surveillance System, an ongoing state-based, random-digit telephone
      survey of the noninstitutionalized U.S. population aged 18 years or older. In
      2001-2002, health-related quality-of-life measures were administered in 23 states
      and the District of Columbia. RESULTS: An estimated 5.1 percent of U.S. adults
      reporting a primary health impairment indicated that a mental health problem was
      the primary cause. Those with a primary mental health impairment were more likely
      than those with a primary physical health impairment to report infrequent
      vitality (less than 14 days in the previous 30 days) and frequent occurrences of
      mental distress, depressive symptoms, and anxiety (at least 14 days in the
      previous 30 days). Relative to those who reported no impairment, persons who
      reported a mental health impairment were more likely to indicate that they
      experienced frequent physical distress and frequent pain. Persons with a primary
      mental health impairment were more likely than those with a primary physical
      health impairment to smoke and drink heavily. No significant difference was found
      in self-reported frequent sleeplessness or fair-to-poor general health between
      persons with a primary mental health impairment and those with a physical health
      impairment. CONCLUSIONS: Mental health impairment is strongly associated with
      reduced health-related quality of life and health behaviors, frequently at levels
      equal to or exceeding those of physical health impairments.

PMID- 15572570
TI  - Psychosocial risk factors associated with suicide attempts and violence among
      psychiatric inpatients.
AB  - OBJECTIVES: To better understand the relationship between suicidal behavior and
      violence directed toward others among patients with major psychiatric disorders,
      this study examined how suicide attempts and violent behaviors were associated
      with various psychosocial problems. METHODS: Participants were inpatients in two
      psychiatric state hospitals. They included 216 inpatients who had physically
      assaulted another patient or a staff member and a comparison group of 81
      inpatients who had not assaulted anyone. History of suicide attempts and
      historical information about various risk factors for violence and suicide were
      obtained through chart review and patient interviews. RESULTS: Patients in the
      violent group did not differ from those in the nonviolent group in whether they
      had attempted suicide. Suicide attempts and violence were associated with
      different historical variables. Suicide attempts were associated with a history
      of head trauma, harsh parental discipline, and parental psychopathology. Violence
      against others was associated with having a history of school truancy and foster
      home placement. CONCLUSIONS: Among inpatients with major psychiatric disorders,
      violence and suicide attempts were not related to each other and were associated
      with dissimilar psychosocial risk factors.

PMID- 15572571
TI  - Should psychologists have prescribing authority?

PMID- 15572572
TI  - Use of health care services and costs of psychiatric disorders among National
      Health Insurance enrollees in Taiwan.
AB  - The National Health Insurance (NHI) database in Taiwan was used to detect the use
      of health care services and the costs of psychiatric disorders among NHI
      enrollees. Data were analyzed for 126,146 enrollees. Four categories were used
      for enrollees: no psychiatric disorder, a minor psychiatric disorder, a major
      psychiatric disorder without catastrophic illness registration, and a major
      psychiatric disorder with catastrophic illness registration (which eliminates
      copayments). Compared with enrollees with a minor psychiatric disorder, those
      with a major psychiatric disorder, either with or without catastrophic illness
      registration, had higher use and costs of mental health care services. Compared
      with enrollees without a psychiatric disorder, those with a minor psychiatric
      disorder or a major psychiatric disorder without catastrophic illness
      registration had higher use and costs of non-mental health care services. Both
      the mental and general health care of persons with psychiatric disorders are
      important.

PMID- 15572573
TI  - Caregiving attitudes and at-risk maternal behavior among mothers with major
      mental illness.
AB  - In an effort to improve parenting assessments for mothers with mental illness,
      this study examined the relationship between caregiving attitudes and maternal
      behavior. Participants included 44 mothers with major mental illness who were
      involved with the child welfare system and their young children. The Parenting
      Opinion Questionnaire (POQ) was administered to assess caregiving attitudes.
      Maternal behavior was assessed directly in a videotaped observation. Unrealistic
      maternal caregiving attitudes, especially attitudes that a child should provide a
      parent with support and comfort, were associated with at-risk maternal behavior.
      The findings support the application of the POQ for use in multimeasure,
      multimethod parenting evaluations.

PMID- 15572574
TI  - Community pharmacists' attitudes toward and professional interactions with users
      of psychiatric medication.
AB  - Consumers of psychiatric medications or services may be stigmatized by health
      care providers. The authors surveyed community pharmacists (N=283) in the greater
      Toronto area to determine their attitudes toward and professional interactions
      with patients who used psychiatric medications and those who used cardiovascular
      medications. Despite generally positive attitudes, pharmacists reported feeling
      more uncomfortable discussing symptoms and medications with patients who have
      mental illness than with patients who have cardiovascular problems. Patients with
      mental illness appeared to receive fewer pharmacy services than patients with
      cardiovascular disorders. Barriers to receipt of counseling included a lack of
      privacy and inadequate training. Adequate training in mental health may be key in
      improving the professional interactions of community pharmacists toward patients
      who use psychiatric medication.

PMID- 15572575
TI  - Age of gambling initiation and severity of gambling and health problems among
      older adult problem gamblers.
AB  - This study examined the relationship between age at first gambling experience and
      severity of gambling and related problems among older adult problem gamblers.
      Fifty-two problem gamblers over the age of 65 years completed self-report
      instruments that assessed gambling problems as well as the Short Form 36 health
      survey. The median age at first gambling experience was 21 years. Compared with
      gamblers who had a late onset of gambling, those with an early onset wagered more
      frequently and had more severe medical and psychiatric problems. These data
      suggest that gambling that begins in adolescence may be associated with an
      elevated severity of problems throughout the life span among older adult problem
      gamblers.

PMID- 15572576
TI  - Voting preferences of outpatients with chronic mental illness in Germany.
AB  - Outpatients with chronic mental illness living in therapeutic residential
      facilities in Mannheim, Germany (N=110) responded to an opinion poll to determine
      their voting preferences for the 2002 federal election to the Bundestag. The poll
      found that the outpatients were significantly more likely than the general
      population in Mannheim to prefer left-wing parties (78 percent compared with 56
      percent). This finding is in contrast to earlier reports; however, it seems to
      better reflect common beliefs about the political preferences of this population.
      In conclusion, persons with chronic mental illness seem to prefer political
      parties that they believe will best serve their perceived specific interests.

PMID- 15572577
TI  - Impractical features of long-acting risperidone.

PMID- 15572579
TI  - Identifying life stressors of patients with schizophrenia at hospital discharge.

PMID- 15572580
TI  - Ethical challenges in the face of a targeted threat.

PMID- 15572581
TI  - Racial variability in haplotype frequencies of UGT1A1 and glucuronidation
      activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an
      African-American.
AB  - Ethnic differences in genetic polymorphisms in UDP-glucuronosyltransferase 1A1
      (UGT1A1) were investigated among African-Americans, Caucasians, and Japanese
      using samples obtained from 150 individuals for each population. Genotyping of 
      3279T>G in the phenobarbital-responsive enhancer module, TA repeats in the TATA
      box, 211G>A (G71R) and 686C>A (P229Q) in exon 1, and three single nucleotide
      polymorphisms (SNPs) (1813C> T, 1941C>G, and 2042C>G) in the 3'-untranslated
      region in exon 5 was performed. Eight haplotypes of block 1 (exon 1 and its 5'
      flanking region) harboring the first four variations were assigned to each
      individual. The dominant haplotype for African-Americans was *28b (-3279G;TA(7);
      211G;686C) (0.446), whereas that for the Japanese was *1a (-3279T;
      TA(6);211G;686C) (0.610). Frequencies of the two haplotypes *1a and *28b were
      comparable in Caucasians. Haplotype *6a (-3279T;TA(6); 211A;686C) was
      characteristic of the Japanese, whereas haplotypes *36b and *37b (-3279T;TA(5)
      and TA(8);211G;686C) were found mostly in African-Americans. Although the three
      SNPs in block 2 (exons 2-5) were in complete linkage in the Japanese, they were
      not completely linked in African-Americans or Caucasians. These differences in
      haplotype distribution patterns among the three populations suggest the
      possibility of ethnic differences in toxicity profiles of drugs detoxicated by
      UGT1A1. A novel SNP, 686C>T (P229L), was found in an African-American. The
      intrinsic clearance of 7-ethyl-10-hydroxycamptothecin (SN-38) by P229L UGT1A1
      expressed in COS-1 cells was about 3% of the wild type. The results of Western
      blotting and real-time reverse transcription-polymerase chain reaction suggest
      that the low glucuronidation activity of the variant was partly due to its low
      stability. The variation 686C>T may cause high toxicity during 7-ethyl-10-[4-(1
      piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) therapy or
      hyperbilirubinemia in patients.

PMID- 15572582
TI  - Transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is a life-threatening adverse
      effect of transfusion that is occurring at increasing incidence in the United
      States and that, in the past 2 reporting years, has been the leading cause of
      transfusion-related death. TRALI and acute lung injury (ALI) share a common
      clinical definition except that TRALI is temporally and mechanistically related
      to the transfusion of blood/blood components. In prospective studies, 2 patient
      groups, 1 requiring cardiac surgery and 1 with hematologic malignancies and
      undergoing induction chemotherapy, were predisposed. Two different etiologies
      have been proposed. The first is a single antibody-mediated event involving the
      transfusion of anti-HLA class I and class II or antigranulocyte antibodies into
      patients whose leukocytes express the cognate antigens. The second is a 2-event
      model: the first event is the clinical condition of the patient resulting in
      pulmonary endothelial activation and neutrophil sequestration, and the second
      event is the transfusion of a biologic response modifier (including lipids or
      antibodies) that activates these adherent polymorphonuclear leukocytes (PMNs),
      resulting in endothelial damage, capillary leak, and TRALI. These hypotheses are
      discussed, as are the animal models and human studies that provide the
      experimental and clinical relevance. Prevention, treatment, and a proposed
      definition of TRALI, especially in the context of ALI, are also examined.

PMID- 15572583
TI  - Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2
      action in the MedB-1 mediastinal lymphoma line.
AB  - Primary mediastinal B-cell lymphoma (PMBL) is a well-defined subtype of diffuse
      large B-cell lymphoma. Molecular cytogenetics revealed frequent gains of 9p24.
      JAK2, mapping in this region, is presently regarded as a candidate oncogene
      because expression profiling showed high Janus kinase-2 (JAK2) transcript levels
      and JAK2 was found to be constitutively phosphorylated in mediastinal B-cell
      lymphomas. We confirm that in the MedB-1 mediastinal B-cell line, harboring a
      trisomy 9, JAK2 transcription is elevated and the product is highly
      phosphorylated. However, JAK2 is not overexpressed at the protein level. On top,
      JAK2 protein turnover is even delayed. This unexpected finding coincides with a
      biallelic mutation of the suppressor of cytokine signaling-1 (SOCS-1) gene in
      this cell, which abrogates SOCS box function of the protein. Ectopic expression
      of wild-type (wt) SOCS-1 in MedB-1 leads to growth arrest and dramatic reduction
      of phospho-JAK2 and its downstream partner phospho-signal transducer and
      activator of transcription-5 (phospho-STAT5). Ultimately, the target gene cyclin
      D1 is repressed in transfectants while RB1, which is silenced in MedB-1, is
      induced. We conclude that, in MedB-1, action of phospho-JAK2 is sustained due to
      defective SOCS-1. Hence, SOCS-1 qualifies as a novel tumor suppressor. Of note,
      SOCS-1 mutations are also present in the parental tumor of MedB-1 and were
      detected in 9 of 20 PMBLs.

PMID- 15572584
TI  - Hematopoietic cells regulate the angiogenic switch during tumorigenesis.
AB  - Hematopoietic cells (HCs) promote blood vessel formation by producing various
      proangiogenic cytokines and chemokines and matrix metalloproteinases. We injected
      mouse colon26 colon cancer cells or human PC3 prostate adenocarcinoma cells into
      mice and studied the localization of HCs during tumor development. HCs were
      distributed in the inner tumor mass in all of the tumor tissues examined;
      however, the localization of HCs in the tumor tissue differed depending on the
      tumor cell type. In the case of colon26 tumors, as the tumor grew, many mature
      HCs migrated into the tumor mass before fine capillary formation was observed. On
      the other hand, although very few HCs migrated into PC3 tumor tissue, c-Kit+
      hematopoietic stem/progenitor cells accumulated around the edge of the tumor.
      Bone marrow suppression induced by injection of anti-c-Kit neutralizing antibody
      suppressed tumor angiogenesis by different mechanisms according to the tumor cell
      type: bone marrow suppression inhibited the initiation of sprouting angiogenesis
      in colon26 tumors, while it suppressed an increase in the caliber of newly
      developed blood vessels at the tumor edge in PC3 tumors. Our findings suggest
      that HCs are involved in tumor angiogenesis and regulate the angiogenic switch
      during tumorigenesis.

PMID- 15572585
TI  - The combination of thalidomide and intermediate-dose dexamethasone is an
      effective but toxic treatment for patients with primary amyloidosis (AL).
AB  - Based on the efficacy of thalidomide in multiple myeloma and on its synergy with
      dexamethasone on myeloma plasma cells, we evaluated the combination of
      thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and
      dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary
      amyloidosis (AL) whose disease was refractory to or had relapsed after first-line
      therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall,
      15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions
      and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5
      8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic
      bradycardia was a common (26%) adverse reaction. The combination of thalidomide
      and dexamethasone is rapidly effective and may represent a valuable second-line
      treatment for AL.

PMID- 15572586
TI  - Inhibiting primary effusion lymphoma by lentiviral vectors encoding short hairpin
      RNA.
AB  - We use lentiviral-delivered RNA interference (RNAi) to inhibit the growth of a
      model of primary effusion lymphoma (PEL) in vitro and in vivo. RNAi is a
      phenomenon allowing the sequence-specific targeting and silencing of exogenous
      and endogenous gene expression and is being applied to inhibit viral replication
      both in vitro and in vivo. We show that silencing of genes believed to be
      essential for the Kaposi sarcoma-associated herpesvirus (KSHV) latent life cycle
      (the oncogenic cluster) has a varied effect in PEL cell lines cultured in vitro,
      however, concomitant silencing of the viral cyclin (vcyclin) and viral FLICE (Fas
      associating protein with death domain-like interleukin-1beta-converting enzyme)
      inhibitory protein (vFLIP) caused efficient apoptosis in all PEL lines tested. We
      demonstrate that in a murine model of PEL, lentiviral-mediated RNA interference
      both inhibits development of ascites and can act as a treatment for established
      ascites. We also show that the administered lentiviral vectors are essentially
      limited to the peritoneal cavity, which has advantages for safety and dosage in a
      therapeutic setting. This shows the use of lentiviral-mediated RNA interference
      in vivo as a potential therapeutic against a virally driven human cancer.

PMID- 15572587
TI  - Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone
      as postremission intensification therapy for acute myeloid leukemia in adults
      under 60 years of age: Cancer and Leukemia Group B Study 9222.
AB  - The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that
      treatment intensification of acute myeloid leukemia (AML) in first remission with
      multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone.
      We enrolled 474 patients younger than 60 years old with untreated de novo AML.
      Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients
      (72%), and 309 of these patients were randomized to receive one of 2 different
      intensification regimens. The first regimen consisted of 3 courses of HiDAC. The
      second regimen consisted of one course of HiDAC, a second course with etoposide
      and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After
      a median follow-up time of 8.3 years, the median survival for all randomized
      patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in
      disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was
      1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95%
      CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was
      the only pretreatment characteristic prognostic for DFS, but there was no
      evidence of a differential treatment effect within cytogenetic risk groups.
      Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens
      produced similar outcomes.

PMID- 15572588
TI  - z-VAD-fmk augmentation of TNF alpha-stimulated neutrophil apoptosis is compound
      specific and does not involve the generation of reactive oxygen species.
AB  - In most cell types constitutive and ligand-induced apoptosis is a caspase
      dependent process. In neutrophils, however, the broad-spectrum caspase inhibitor
      z-VAD-fmk enhances tumor necrosis factor-alpha (TNF alpha)-induced cell death,
      and this has been interpreted as evidence for caspase-dependent and -independent
      cell death pathways. Our aim was to determine the specificity of the effect of z
      VAD-fmk in neutrophils and define the potential mechanism of action. While
      confirming that z-VAD-fmk (> 100 microM) enhances TNF alpha-induced neutrophil
      apoptosis, lower concentrations (1-30 microM) completely blocked TNF alpha
      stimulated apoptosis. Boc-D-fmk, a similar broad-spectrum caspase inhibitor, and
      z-IETD-fmk, a selective caspase-8 inhibitor, caused a concentration-dependent
      inhibition of only TNF alpha-stimulated apoptosis. Moreover, the caspase-9
      inhibitor, Ac-LEHD-cmk, had no effect on TNF alpha-induced apoptosis, and z-VAD
      fmk and Boc-D-fmk inhibited TNF alpha-stimulated reactive oxygen species (ROS)
      generation. These data suggest that TNF alpha-induced apoptosis in neutrophils is
      fully caspase dependent and uses a mitochondrial-independent pathway and that the
      proapoptotic effects of z-VAD-fmk are compound specific and ROS independent.

PMID- 15572589
TI  - The origins of age-related proinflammatory state.
AB  - We hypothesized that the rising levels of inflammatory markers with aging is
      explained by cardiovascular risk factors and morbidity becoming progressively
      more prevalent in older persons. Information on inflammatory markers,
      cardiovascular risk factors, and diseases was collected in 595 men and 748 women
      sampled from the general population (age, 20-102 years). In both men and women,
      older age was associated with higher levels of interleukin-6 (IL-6), IL-1
      receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen,
      while soluble IL-6 receptor (sIL-6r) increased significantly with age only in
      men. Adjusting for cardiovascular risk factors and morbidity, the age regression
      coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL
      18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for
      cardiovascular morbidity substantially reduced the effect of age on CRP in men
      but not in women. Findings were confirmed in a subgroup of 51 men and 45 women
      with low risk profile and no cardiovascular morbidity. Part of the
      "proinflammatory state" in older persons is related to the high prevalence of
      cardiovascular risk factor and morbidity.

PMID- 15572590
TI  - Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(
      )CD8- double-negative regulatory T cells.
AB  - Down-regulation of immune responses by regulatory T (Treg) cells is an important
      mechanism involved in the induction of tolerance to allo-antigens (Ags).
      Recently, a novel subset of Ag-specific T-cell receptor (TCR)alpha beta+ CD4(
      )CD8- (double-negative [DN]) Treg cells has been found to be able to prevent the
      rejection of skin and heart allografts by specifically inhibiting the function of
      antigraft-specific CD8+ T cells. Here we demonstrate that peripheral DN Treg
      cells are present in humans, where they constitute about 1% of total CD3+ T
      cells, and consist of both naive and Ag-experienced cells. Similar to murine DN
      Treg cells, human DN Treg cells are able to acquire peptide-HLA-A2 complexes from
      antigen-presenting cells by cell contact-dependent mechanisms. Furthermore, such
      acquired peptide-HLA complexes appear to be functionally active, in that CD8+ T
      cells specific for the HLA-A2-restricted self-peptide, Melan-A, became sensitive
      to apoptosis by neighboring DN T cells after acquisition of Melan-A-HLA-A2
      complexes and revealed a reduced proliferative response. These results
      demonstrate for the first time that a sizable population of peripheral DN Treg
      cells, which are able to suppress Ag-specific T cells, exists in humans. DN Treg
      cells may serve to limit clonal expansion of allo-Ag-specific T cells after
      transplantation.

PMID- 15572591
TI  - Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in
      a dose-dependent manner.
AB  - The tyrosine kinase inhibitor imatinib (imatinib, STI571, Glivec, and Gleevec) is
      increasingly used in patients undergoing allogeneic transplantation for leukemia.
      However, little is known regarding its potential immunoregulatory effects. Here,
      we investigate the effect of imatinib on T-cell receptor (TCR)-mediated
      activation of human T cells. Following stimulation with the anti-CD3 antibody
      12F6, proliferation of activated T cells was almost completely inhibited by 10
      microM imatinib. Furthermore, antigen-triggered expansion of CD8+ T cells in
      response to immunodominant cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
      peptides was significantly reduced. Up-regulation of the activation markers CD25
      and CD69 in response to TCR cross-linking was suppressed by imatinib at a mean
      inhibitory concentration 50% (IC50) of 5.4 microM and 7.3 microM, respectively;
      interleukin 2 (IL-2) production was also impaired. Analysis of the TCR-induced
      signaling cascade showed that imatinib substantially reduced tyrosine
      phosphorylation of ZAP70 and LAT in response to activation through the TCR.
      Sequence comparisons of all 90 tyrosine kinase genes in the human genome for
      homology in the adenosine triphosphate (ATP) binding pocket identified LCK, which
      is required for ZAP70 activation, as a likely target for imatinib. The IC50 for
      LCK inhibition by imatinib was 0.6 microM to 0.8 microM in an in vitro tyrosine
      kinase assay. In summary, imatinib can interfere with T-cell activation in vitro,
      and its impact on the frequency of opportunistic infections and graft-versus-host
      or graft-versus-leukemia reactions after transplantation should be investigated
      in clinical trials.

PMID- 15572592
TI  - Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase
      (IDO)-producing dendritic cells: too much ado about IDO?
AB  - Although dendritic cells (DCs) strongly stimulate the immune response, they can
      also induce unresponsiveness. Recently, a human monocyte-derived DC subpopulation
      was described that constitutively expresses indoleamine 2,3-dioxygenase (IDO).
      These DCs were defined as nonadherent CD123+/CC chemokine receptor 6+ (CCR6+)
      cells that suppress the allogeneic T-cell response. In the present study, we
      generated nonadherent, mature DCs from human blood monocytes. As expected, in
      addition to the classic markers, these cells expressed CD123 and CCR6. Reverse
      transcription-polymerase chain reaction (RT-PCR), however, did not show IDO gene
      transcription, nor did we detect enzymatic IDO activity. Treating the cells with
      interferon-gamma (IFN-gamma) resulted in significant IDO production.
      Subsequently, we studied the regulatory properties of IDO-producing DCs on
      autologous and allogeneic T-cell responses. Neither OKT3-stimulated T cells of
      healthy donors nor myelin basic protein (MBP)-specific T cells of patients with
      multiple sclerosis (MS) were suppressed by autologous IDO DCs. However, whereas
      IDO(neg) DCs supported further stimulation of preactivated MBP-specific T cells
      of an MS patient, IDO(pos) DCs had lost this capacity. The allogeneic T-cell
      response was only marginally suppressed by IDO DCs. Our findings show that
      nonadherent CD123+/CCR6+ human DCs do not constitutively express IDO, and, even
      if they express the enzyme after IFN-gamma treatment, they possess only limited T
      cell regulatory function.

PMID- 15572593
TI  - Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic
      leukemia occurs downstream of ligand-induced nuclear translocation of the
      glucocorticoid receptor.
AB  - Glucocorticoids are among the most effective agents used in the treatment of
      childhood acute lymphoblastic leukemia (ALL), and patient response to treatment
      is an important determinant of long-term outcome. Despite its clinical
      significance, the molecular basis of glucocorticoid resistance in lymphoid
      malignancies is still poorly understood. We have recently developed a highly
      clinically relevant experimental model of childhood ALL, in which primary
      childhood ALL biopsies were established as xenografts in nonobese diabetic/severe
      combined immunodeficient (NOD/SCID) mice. The in vivo and in vitro responses of a
      panel of these xenografts to the glucocorticoid, dexamethasone, reflected the
      outcome of the patients from whom they were derived. In this report we show that
      glucocorticoid resistance in B-cell precursor (BCP) ALL xenografts was not due to
      down-regulation of the glucocorticoid receptor (GR) nor to defective ligand
      binding of the GR. Moreover, dexamethasone-induced GR translocation from the
      cytoplasm to the nucleus was comparable in all xenografts. However,
      glucocorticoid resistance was associated with profoundly attenuated induction of
      the BH3-only proapoptotic protein, Bim, when xenograft cells were exposed to
      dexamethasone. These results show that dexamethasone resistance in BCP ALL
      xenografts occurs downstream of ligand-induced nuclear translocation of the GR,
      but upstream of Bim induction.

PMID- 15572594
TI  - Frizzled 9 knock-out mice have abnormal B-cell development.
AB  - The binding of frizzled (Fzd) receptors by their Wnt ligands results in the
      inhibition of beta-catenin degradation and subsequent transcription of beta
      catenin/LEF-inducible genes. The beta-catenin pathway is known to be involved in
      development, tumorigenesis, and stem cell self-renewal. In humans, the FZD9 gene
      lies in the region of chromosome 7q11.23 deleted in the neurodevelopmental
      disorder, Williams-Beuren syndrome (WBS). Fzd9-/- mice show no obvious features
      of WBS, but reveal a role for Fzd9 in lymphoid development and maturation. Fzd9-/
      mice show pronounced splenomegaly, thymic atrophy, and lymphadenopathy with age,
      with accumulation of plasma cells in lymph nodes. There is a depletion of
      developing B cells in the bone marrow (BM), particularly in the pre-B stage where
      immunoglobulin heavy chains are expressed and the cells are undergoing clonal
      expansion prior to light chain rearrangement. The pre-B defect is partially
      intrinsic to the hematopoietic system; as in competitive BM reconstitution
      studies, Fzd9-/- -derived BM exhibits defective B-cell development when implanted
      into a wild-type host. Mature B cells are present in normal numbers in lymph node
      and spleen. These findings suggest a role for Fzd9 signaling in lymphoid
      development, particularly at points where B cells undergo self-renewal prior to
      further differentiation.

PMID- 15572595
TI  - Imatinib mesylate therapy may overcome the poor prognostic significance of
      deletions of derivative chromosome 9 in patients with chronic myelogenous
      leukemia.
AB  - Deletions of derivative chromosome 9 [der(9)] can be identified by fluorescence
      in situ hybridization (FISH) in 10% to 15% of patients with chronic myeloid
      leukemia (CML). Patients with der(9) deletions have been reported to have an
      adverse outcome when treated with chemotherapy, interferon, and possibly imatinib
      mesylate. We investigated the frequency and prognostic significance of der(9)
      deletions among 352 patients with CML treated with imatinib mesylate at our
      institution, in whom a deletion status of der(9) was determined. Thirty-three
      patients (9%; 95% CI 0.07, 0.13) (30 in chronic phase, 3 in accelerated phase)
      had der(9) deletions. The rates of major (82% vs 79%, P = 0.82) and complete
      cytogenetic response (76% vs 66%, P = .33) with imatinib mesylate therapy were
      similar in patients with and without der(9) deletions, respectively. After a
      median follow-up of 28 months, there was no difference in overall survival (P =
      .30) or response duration (P = .49) in patients with and without deletions. In a
      multivariate analysis, der(9) deletions had no significant impact on response,
      survival, or response duration. We conclude that treatment with imatinib mesylate
      overcomes the adverse prognostic significance of der(9) deletions in patients
      with CML.

PMID- 15572596
TI  - Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem
      cells capable of rapidly reconstituting and rescuing myeloablated transplant
      recipients.
AB  - In clinical bone marrow transplantation, the severe cytopenias induced by bone
      marrow ablation translate into high risks of developing fatal infections and
      bleedings, until transplanted hematopoietic stem and progenitor cells have
      replaced sufficient myeloerythroid offspring. Although adult long-term
      hematopoietic stem cells (LT-HSCs) are absolutely required and at the single-cell
      level sufficient for sustained reconstitution of all blood cell lineages, they
      have been suggested to be less efficient at rapidly reconstituting the
      hematopoietic system and rescuing myeloablated recipients. Such a function has
      been proposed to rather be mediated by less well-defined short-term hematopoietic
      stem cells (ST-HSCs). Herein, we demonstrate that Lin(-)Sca1(+)kit(hi)CD34+ short
      term reconstituting cells contain 2 phenotypically and functionally distinct
      subpopulations: Lin(-)Sca1(+)kit(hi)CD34(+)flt3- cells fulfilling all criteria of
      ST-HSCs, capable of rapidly reconstituting myelopoiesis, rescuing myeloablated
      mice, and generating Lin(-)Sca1(+)kit(hi)CD34(+)flt3+ cells, responsible
      primarily for rapid lymphoid reconstitution. Representing the first commitment
      steps from Lin(-)Sca1(+)kit(hi) CD34(-)flt3- LT-HSCs, their identification will
      greatly facilitate delineation of regulatory pathways controlling HSC fate
      decisions and identification of human ST-HSCs responsible for rapid
      reconstitution following HSC transplantations.

PMID- 15572597
TI  - Engraftment and survival following reduced-intensity allogeneic peripheral blood
      hematopoietic cell transplantation is affected by CD8+ T-cell dose.
AB  - The influence of graft composition on clinical outcomes after reduced-intensity
      conditioning is not well-characterized. In this report we prospectively
      enumerated CD34+, CD3+, CD4+, and CD8+ cell doses in granulocyte colony
      stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC)
      allografts in 63 patients who received transplants following non-myeloablative
      conditioning with total body irradiation 200 cGy plus fludarabine as treatment
      for malignant diseases. Donors were HLA-identical siblings (n = 38) or HLA
      matched unrelated individuals (n = 25). By univariate analyses G-PBMC CD8+ T-cell
      dose in at least the 50th percentile favorably correlated with full donor blood T
      cell chimerism (P = .03), freedom from progression (P = .001), and overall
      survival (P = .01). No G-PBMC cell dose influenced grade II to IV acute or
      extensive chronic graft-versus-host disease. In multivariate analysis only G-PBMC
      CD8+ T-cell dose (P = .003; RR = 0.2, 95% CI = 0.1-0.6) was associated with
      improved freedom from progression. Infusion of low G-PBMC CD8+ T-cell dose for
      reduced-intensity allografting may adversely affect T-cell engraftment and
      survival outcome.

PMID- 15572598
TI  - A role for bone marrow-derived cells in the vasculature of noninjured CNS.
AB  - The contribution of hematopoietic cells to the formation of blood vessels is
      currently the focus of intense scrutiny. Bone marrow-derived endothelial
      progenitor cells are thought to generate endothelial cells in many tissues,
      including myocardium, muscle, and certain tumors. In the central nervous system
      (CNS), however, the possible role of bone marrow-derived angiocompetent cells
      remains unclear. Here we have investigated the long-term involvement of bone
      marrow-derived cells in the maintenance of endothelial structures in the brain,
      spinal cord, and retina. Using hematopoietic chimeras stably expressing green
      fluorescent protein (GFP) in bone marrow-derived tissues, we found large numbers
      of hematopoietic cells closely associated with vessels in the CNS. None of these
      cells, however, showed an endothelial phenotype. They were positive for monocytic
      and microglial surface markers and demonstrated active phagocytosis of
      neighboring endothelial elements. Bone marrow-derived, vasculature-associated
      cells in the noninjured adult CNS are distinct from endothelial cells, but play
      an active role in vascular structures.

PMID- 15572599
TI  - Interaction between tadalafil and itraconazole.

PMID- 15572600
TI  - Death of twins after intravenous varicella zoster immunoglobulin.

PMID- 15572601
TI  - The impact of new drug introduction on drug expenditure in primary health care in
      Catalunya, Spain.
AB  - BACKGROUND: Introduction of new drugs is a dynamic process with a high impact on
      consumption and expenditure. OBJECTIVE: To analyze the prescription of new drugs
      and the associated costs in public health care in Catalunya, Spain, in 2002. The
      analysis also attempts a perspective of consumption in relation to the grade of
      therapeutic innovation of the new drugs. METHODS: Prescription data on all 86 new
      drugs licensed for use during 1998-2002 were analyzed, using the prescription
      item as unit and the cost. RESULTS: Prescription for new drugs in 2002
      represented 4% of overall items prescribed and 13% of the cost. The mean new drug
      item cost was 39, while that of overall drugs was 13. New drug item increase over
      the previous year was 18.6% compared with 5.2% of the overall drugs, and the
      proportional cost increased by 25.7% and 9.9%, respectively. Ten new drugs
      represented 55.1% of the expenditure of this group. Antiasthmatic drugs
      represented 20.7% of the expenditure on new drugs, angiotensin-receptor blockers
      represented 18.6%, antiaggregants 9.7%, and nonsteroidal antiinflammatory drugs
      6.9%. New drugs providing significant or modest therapeutic improvement
      represented 25.6% of overall new drug items and 32.3% of their cost. CONCLUSIONS:
      New drugs have a mean cost growth rate greater than that of existing drugs, with
      only a quarter of them offering advantages over existing drugs. More detailed
      evaluations of new medications are warranted before they can be recommended for
      general use so that a better distribution of the limited resources available may
      be made when prescribing drugs that are newly available through prescription.

PMID- 15572602
TI  - High- versus low-dose oxytocin for augmentation or induction of labor.
AB  - OBJECTIVE: To compare the use of high- and low-dose oxytocin for augmentation or
      induction of labor. DATA SOURCES: Clinical trials were accessed through MEDLINE
      (1966-November 2003). Published literature relevant to the use of oxytocin for
      augmentation or induction of labor was evaluated. STUDY SELECTION AND DATA
      EXTRACTION: Articles identified from the data sources were evaluated and included
      if they were clinical trials comparing high-versus low-dose oxytocin for
      augmentation or induction of labor. DATA SYNTHESIS: Oxytocin is a treatment of
      choice for augmentation and induction of labor; however, no consensus exists
      regarding optimal dosing. Relevant studies comparing high-dose (2-6 mU/min) and
      low-dose (1-2 mU/min) therapy for labor augmentation and induction were
      evaluated. CONCLUSIONS: High-dose oxytocin decreases the time from admission to
      vaginal delivery, but does not appear to decrease the incidence of cesarean
      sections when compared with low-dose therapy.

PMID- 15572603
TI  - Agranulocytosis associated with nitrofurantoin therapy.

PMID- 15572604
TI  - Antimuscarinic intoxication resulting from the ingestion of moonflower seeds.
AB  - OBJECTIVE: To report a case in which ingestion of moonflower seeds resulted in
      antimuscarinic intoxication. CASE SUMMARY: An 18-year-old man was found at a
      local convenience store hallucinating and incoherent. Upon presentation to the
      emergency department, his signs and symptoms included tachycardia, confusion,
      dilated pupils, and dry, flushed, hot skin. He was admitted to the intensive care
      unit. Hallucinations and symptoms resolved within 36-48 hours after
      hospitalization. The patient then reported that he had ingested moonflower seeds.
      He recovered and was released 4 days after admission. DISCUSSION: Based on the
      patient's description and clinical presentation, the moonflower seeds were
      believed to be Datura inoxia. This species of plant is similar to jimson weed, or
      Datura stramonium. These plants are known to contain high concentrations of
      anticholinergic substances; ingestion can result in anticholinergic intoxication.
      Signs and symptoms that commonly occur include hallucinations, tachycardia,
      dilated pupils, and disorientation. In our patient, use of the Naranjo
      probability scale indicated a possible relationship between the moonflower seed
      ingestion and the patient's signs and symptoms. CONCLUSIONS: Ingestion of the
      Datura species can result in severe toxicity. Each plant varies in the
      concentrations of alkaloid substances. For this reason, it is very important for
      individuals to become educated on the toxicities and potential risks associated
      with recreational use of these plants.

PMID- 15572605
TI  - Improving men's sexual health: a challenge for today.

PMID- 15572607
TI  - Lack of recent condom use among detained adolescent males: a multilevel
      investigation.
AB  - OBJECTIVE: To investigate multiple levels of influence with respect to the lack
      of recent condom use among a high risk sample of adolescent males recruited from
      short term detention facilities. METHODS: A cross sectional survey of 231
      adolescent males serving, predominantly, short term detention sentences.
      Assessments were conducted using audiocomputer assisted self interviewing. Condom
      use during the most recent sexual event was assessed as well as 20 potential
      correlates of not using condoms. Correlates were assessed within five levels of
      causation: personal, relational, peer affiliation, family, and societal. RESULTS:
      Nine correlates achieved bivariate significance (p<0.05). Of these, the personal
      level correlates were particularly important in a multivariate model. The
      motivation subscale from the Condom Barriers Scale was the strongest multivariate
      correlate of recent condom use. Adolescents scoring below the median were about
      3.4 times more likely to report lack of recent condom use (p=0.0006). Adolescents
      indicating they had ever caused a pregnancy were about 2.5 times more likely to
      report lack of condom use (p=0.02). Finally, those reporting their peers did not
      use condoms were about twice as likely to report lack of use (p=0.048).
      CONCLUSION: Upon investigating multiple levels of potential influence on condom
      use, the multivariate findings suggest that personal level factors may be the
      most important determinant of non-use among adolescent males in short term
      detention facilities. Although structural changes may be needed to influence some
      forms of safer sex behaviour, direct intervention with adolescent males may be
      justified to favourably alter determinants of condom use.

PMID- 15572608
TI  - Fifty ways to leave your rubber: how men in Mombasa rationalise unsafe sex.
AB  - OBJECTIVE: To explore the reasons why men who have sex with sex workers in Kenya
      refuse to use condoms in order to develop potential interventions that might help
      to overcome these barriers. METHODS: We conducted participant observations over a
      period of 2 months in the bars, discos, shebeens, and guesthouses of Mombasa,
      Kenya, where many of the sexual transactions are initiated. RESULTS: Analysis of
      the participant observations revealed at least 50 reasons for not using a condom,
      which we grouped into six categories: condoms are not pleasurable, condoms are
      defective, condoms are harmful, condoms are unnecessary, condoms are too hard to
      use, and external forces prohibit using condoms. CONCLUSIONS: Some of the reasons
      men say they do not use condoms would be difficult to affect directly. Others are
      the result of gaps in knowledge and have not been impacted through better
      communication strategies. Finally, some of the reasons for not using condoms,
      such as men's weaknesses, and the loss of pleasure, could possibly be addressed
      through the introduction of female controlled devices. However, the most
      important conclusion of this paper is that men who pay for sex do so because it
      is pleasurable and many men do not find the male condom pleasurable. Therefore,
      messages targeted at men who have sex with sex workers may not be 100% successful
      if they only emphasise the benefits of condom use as disease control.

PMID- 15572609
TI  - Sexual patterning and condom use among a group of HIV vulnerable men in Thika,
      Kenya.
AB  - BACKGROUND/AIM: A composite sample of 37 peer educators and 215 members of self
      help groups of male informal sector workers in Thika, Kenya, targeting HIV/AIDS
      prevention, were interviewed about their sexual behaviour, using a customised
      template, as part of a broader survey on gender attitudes and peer pressure.
      METHOD: Details on each sexual partner reported by each man over a 12 month
      recall period included type of partner, months during which sexual relations took
      place, and condom use. RESULTS: The men reported 471 sexual partners over the
      recall period, with a range of 0-16 partners, and an average of just under two
      partners. 8% of men had had no sexual partner, half were monogamous, and 3% had
      multiple partners with whom they used condoms exclusively, leaving 39% at varying
      degrees of risk. Condom use increased significantly with reduced intimacy of
      partner. 16% of men reported having at least one liaison with a female sex worker
      and two thirds of such liaisons were exclusively protected by condom use.
      Younger, single men had significantly more partners, but were more likely to use
      condoms. Duration of membership in self help groups was strongly associated with
      exclusive use of condoms with casual or FSW partners. Recorded attitudes
      corresponded somewhat with practice, but the data showed large gaps between the
      two, and low levels of gender sensitivity. CONCLUSION: There is some evidence
      that group membership has resulted in increased condom use and partner reduction,
      but there are doubts as to the extent to which the "ABC" strategy can be
      successful in stemming the HIV/AIDS epidemic. It may be necessary for
      interventions to target contextual issues, particularly gender relations, if the
      approach is to be more successful.

PMID- 15572610
TI  - The association between gang involvement and sexual behaviours among detained
      adolescent males.
AB  - OBJECTIVE: Data were collected from 270 detained male adolescents (aged 14-18
      years) to determine the association between ever having been in a gang and a
      range of sexual behaviours such as sexual activity, male condom use, sex with
      multiple partners, and drug use during sex. METHODS: Participants answered survey
      questions using audio computer assisted self interviewing (A-CASI) procedures,
      which assessed demographic, family factors, history of gang membership, and
      sexual behaviours. RESULTS: Multiple logistic regression analyses, controlling
      for demographic, socioeconomic status, and family factors, indicated that
      adolescents who reported having been in a gang, relative to their peers reporting
      no gang involvement, were 5.7 times more likely to have had sex, 3.2 times more
      likely to have got a girl pregnant, and almost four times more likely to have
      been "high" on alcohol or other drugs during sexual intercourse, have had sex
      with a partner who was "high" on alcohol or other drugs, or have had sex with
      multiple partners concurrently. CONCLUSIONS: Findings suggest that having been in
      a gang can discriminate between levels of STI associated risk behaviours among an
      otherwise high risk population-detained adolescent males.

PMID- 15572611
TI  - HIV, sexual risk, and ethnicity among men in England who have sex with men.
AB  - OBJECTIVES: To examine ethnic group differences in HIV testing history and sexual
      HIV risk behaviours that may account for such differences, among men in England
      who have sex with men (MSM), in order to inform HIV prevention planning
      priorities. METHODS: A self completion survey in the summer of 2001 was carried
      out in collaboration with community based health promoters. Three recruitment
      methods were used: "gay pride" festivals, health promoter distributed leaflets,
      internet version advertised with gay service providers. The leaflet was produced
      with an alternative cover for targeted recruitment of black men. RESULTS: In a
      sample of 13,369 MSM living in England, 17.0% were from minority ethnic groups
      and 5.4% had tested HIV positive. Compared to the white British majority, Asian
      men were 0.32 times as likely to be living with diagnosed HIV infection, while
      black men were 2.06 times as likely to be doing so. Among men who had not tested
      HIV positive, Asian men were less likely to have sex with a known HIV positive
      partner, while black men were more likely to have insertive unprotected anal
      intercourse both with a partner they knew to be HIV positive and with a partner
      whose HIV status they did not know. CONCLUSIONS: Among MSM in England, HIV
      prevalence is higher among black men and lower among Asian men compared with the
      white British majority. Increased sexual HIV risk behaviour, especially exposure
      during insertive anal intercourse, accounts for some of this difference. HIV
      prevention programmes for MSM and African people should both prioritise black
      MSM.

PMID- 15572612
TI  - Trends in sexual behaviour among London homosexual men 1998-2003: implications
      for HIV prevention and sexual health promotion.
AB  - OBJECTIVES: To examine changes in sexual behaviour among London homosexual men
      between 1998 and 2003 by type and HIV status of partner. METHODS: Homosexual men
      (n=4264) using London gyms were surveyed annually between 1998 and 2003 (range
      498-834 per year). Information was collected on HIV status, unprotected anal
      intercourse (UAI) in the previous 3 months, and type of partner for UAI. High
      risk sexual behaviour was defined as UAI with a partner of unknown or discordant
      HIV status. RESULTS: Between 1998 and 2003, the percentage of men reporting high
      risk sexual behaviour with a casual partner increased from 6.7% to 16.1%
      (adjusted odds ratio (AOR) 1.36 per year, 95% confidence interval (CI) 1.26 to
      1.46, p <0.001). There was no significant change in the percentage of men
      reporting high risk sexual behaviour with a main partner alone (7.8%, 5.6%,
      p=0.7). These patterns were seen for HIV positive, negative and never tested men
      alike regardless of age. The percentage of HIV positive men reporting UAI with a
      casual partner who was also HIV positive increased from 6.8% to 10.3% (AOR 1.27,
      95% CI 1.01 to 1.58, p <0.05). CONCLUSION: The increase in high risk sexual
      behaviour among London homosexual men between 1998 and 2003 was seen only with
      casual and not with main partners. STI/HIV prevention campaigns among London
      homosexual men should target high risk practices with casual partners since these
      appear to account entirely for the recent increase in high risk behaviour.

PMID- 15572613
TI  - Associations between the sexual behaviour of men who have sex with men and the
      structure and composition of their social networks.
AB  - OBJECTIVE: This exploratory study identified associations between the number of
      sexual partners reported by men who have sex with men (MSM) and the structure and
      composition of their social networks. METHODS: A cross sectional survey was
      conducted of men recruited as key informants, through advertising and chain
      referral. A face to face interview was conducted with 206 MSM. The interview
      included information on the number of sexual partners in the previous year and
      sociodemographic and behavioural characteristics of the participant. Social
      networks were enumerated and network size and density were calculated. Ordered
      logistic regression was used to assess the associations between number of sexual
      partners and personal and network characteristics. RESULTS: The number of anal
      sex partners reported was higher if the participant had injected drugs in the
      past year rather than never having injected (odds ratio, 95% confidence interval:
      3.23, 1.28 to 8.15), decreased with network density (0.014, 0.002 to 0.008) and
      increased if the network did not comprise only HIV negative people (1.77, 1.05 to
      2.99). The number of additional oral sex partners increased with network size
      (1.06, 1.02 to 1.10) and decreased with increased network density (0.034, 0.006
      to 0.205). In addition to similar effects of network size (1.05, 1.01 to 1.09)
      and network density (0.086, 0.013 to 0.563) the model for the number of
      additional manual sex partners also included age (1.03, 1.01 to 1.05).
      CONCLUSION: The density of the social networks of MSM appears strongly and
      consistently associated with patterns of sexual behaviour. This underlines the
      importance of using network approaches to understanding the sexual behaviour of
      MSM and their potential value in identifying novel strategies for intervention.

PMID- 15572614
TI  - HIV related behaviours and attitudes among Chinese men who have sex with men in
      Hong Kong: a population based study.
AB  - OBJECTIVE: This study was conducted in order to determine the prevalence of men
      having sex with men (MSM) and their HIV related behaviours and attitudes among
      Chinese men in Hong Kong. METHODS: A large scale, random, population based,
      anonymous telephone survey of 14 963 men between the ages of 18-60 was conducted.
      The overall response rate was approximately 57%. RESULTS: Of the respondents,
      4.6% had ever engaged in MSM activity. In the 6 months preceding the survey, 2.0%
      had engaged in MSM behaviours (active MSM) and 0.5% reported having engaged in
      anal sex MSM behaviours. Among anal sex MSM, consistent condom use was 42.9% with
      male non-commercial sex partners and even lower with male commercial sex partners
      (35.7%). Approximately 11% of anal sex MSM and 4.1% of the non-anal sex MSM had
      contracted an STD in the last 6 months. The prevalence of HIV testing was only
      20.6% among anal sex MSM and 11.9% among non-anal sex MSM. CONCLUSIONS: Active
      MSM in Hong Kong are at high risk of HIV infection. The belief of low
      vulnerability to HIV is prevalent among active MSM in Hong Kong with only 2.0%
      believing that their chances of HIV infection as being "very likely."

PMID- 15572615
TI  - Use of recreational Viagra among men having sex with men.
AB  - OBJECTIVE: Given the potential for Viagra (sildenafil) use to foster greater
      friction during sex (owing to enlarged erection size) and prolonged sex, the
      recreational use of this substance warrants investigation in the context of STI
      risk. Thus, an exploratory study was conducted to identify bivariate correlates
      of recreational (non-prescription) Viagra use among men who have sex with men
      (MSM) attending a popular sex resort for men located in the southern United
      States. METHODS: A cross sectional study was conducted. Behavioural measures,
      including Viagra use, were assessed using a 3 month recall period. RESULTS: Of
      164 men asked to participate, 91% completed a self administered questionnaire.
      Men resided in 14 states, most of which were located in the southern United
      States. Their average age was 40 years. Most (93%) men self identified as white.
      The median annual income interval was $25,000 to $50,000. One sixth (16.7%)
      reported being HIV positive. 16% reported using non-prescription Viagra. Age
      (p=0.41), income (p=0.32), and HIV serostatus (p=0.85) were not associated with
      Viagra use. Of men recently using ecstasy during sex, 35% reported Viagra use
      compared to 13% among those not using ecstasy (p=0.01). Of men recently using
      cocaine during sex, 37% reported Viagra use compared to 13% among those not using
      cocaine (p=0.009). Use of "poppers" approached, but did not achieve, statistical
      significance as a correlate of Viagra use (p=0.06). Recent frequency of
      unprotected anal sex (p=0.79), fisting (p=0.10), rimming (p=0.64), and having
      five or more sex partners (p=0.09) were not associated with Viagra use.
      CONCLUSION: Recreational Viagra use was relatively common among men, regardless
      of age or HIV serostatus. Viagra use was associated with men's substance abuse
      behaviours rather than their sexual risk behaviours.

PMID- 15572616
TI  - Sexual trauma associated with fisting and recreational drugs.
AB  - There is a rising trend in high risk sexual behaviour among men who have sex with
      men (MSM), with concomitant use of recreational drugs. Activities include fisting
      and unprotected anal intercourse with a partner who is HIV serodiscordant or of
      unknown status. We describe three cases of HIV positive MSM who have recently
      attended our unit as a result of complications secondary to fisting.

PMID- 15572617
TI  - Male genital hygiene beliefs and practices in Nairobi, Kenya.
AB  - OBJECTIVES: Attitudes and practices concerning genital hygiene may influence
      topical microbicide use by men. This study examines knowledge and behaviours
      related to hygiene, genital hygiene, circumcision and hygiene, and to genital
      hygiene before and after sex among men in Nairobi, Kenya. METHODS: We conducted
      463 interviews of men recruited by respondent driven sampling techniques and 10
      focus group discussions with a subsample of 100 volunteers from this group. Men
      were asked individual quantitative survey and qualitative group discussion
      questions about general hygiene behaviours, genital hygiene, and the temporal
      relation of genital hygiene behaviours to sexual encounters. RESULTS: Bathing
      once daily was associated with education, income, and inside tap water. Genital
      washing aside from regular bathing and washing before sex ever were negatively
      associated with bathroom crowding. Genital hygiene before the most recent sexual
      encounter was uncommon and negatively associated with HIV risk perception,
      bathroom crowding, and ethnicity. Men believed genital hygiene before sex would
      arouse suspicions of infidelity or cool sexual ardour. Genital hygiene after sex
      was associated with education, religion, and having inside tap water. Genital
      hygiene after the most recent sexual encounter was associated with age, income,
      and with men having at least one child. CONCLUSIONS: Genital hygiene behaviours
      were associated with resource access factors and group discussions suggest that
      they are modulated by interactions in sexual partnerships. Topical microbicides
      may improve hygiene before and after sex.

PMID- 15572618
TI  - Are we getting the message across? Trends among young men attending an inner city
      young people's clinic.
AB  - BACKGROUND: A young people's clinic has been running at the Archway Sexual Health
      Clinic since 1997. This offers a weekly walk-in service to both young men and
      women under 20 years old. OBJECTIVES: To review the audit data of over 7 years'
      experience from the dedicated young people's clinic at the Archway Sexual Health
      Clinic, the "Arch." METHODS: These data were collected by retrospective notes
      review of a consecutive series of all male attendees over a 7 year period from
      1997 to the end of 2003 with collection of data in Microsoft Excel database.
      RESULTS: These figures show an overall increase in attendee numbers, but also a
      relative rise in the numbers of young men using the service. A high number of
      bacterial sexually transmitted infections were detected. In 2001 and 2003
      respectively, 14.5% and 17.8% of the young men using the service were diagnosed
      with Chlamydia trachomatis. A user survey aimed to identify factors that may be
      encouraging the young men to access the service. CONCLUSIONS: Responding to the
      views of young men using the service has played a part in service development.
      Initiatives at the "Arch" such as the condom policy and choice of gender of staff
      may be factors encouraging increasing attendances. Continuing to work with other
      agencies to develop ways to engage young men are recommended. Word of mouth
      recommendation cannot be underestimated in publicising the service.

PMID- 15572619
TI  - The 374 clinic: an outreach sexual health clinic for young men.
AB  - OBJECTIVES: To describe the establishment of a community based walk-in outreach
      genitourinary medicine clinic, the "374 clinic," in south London to target young
      men under 25 in an area with high rates of sexually transmitted infections
      (STIs). METHODS: The outreach clinic was set up within a Brook advisory centre,
      which already had gained the trust of local young people. Epidemiological,
      clinical, and laboratory data were obtained retrospectively for the first 24
      weeks of the service. RESULTS: 134 attendances were recorded, including 94 new
      and 10 rebook events. The age range of the young men seen was 12-27 years (mean
      18.2 years), the patients were mainly from black and ethnic minority groups, and
      all but one were heterosexual. Most men had heard about the clinic by "word of
      mouth," recommendation by Brook staff or through clinic promotional material.
      Condoms were used more frequently with non-regular sexual partners than with
      regular partners. The uptake of screening for gonococcal and chlamydial
      infections, mostly by urine based molecular techniques, was 98%. The uptake for
      HIV testing in men aged 16 or more was 72%. An overall STI prevalence rate of 26%
      was detected in the clinic population, which consisted almost equally of
      asymptomatic and symptomatic patients. The most prevalent STI was chlamydial
      infection (12%). CONCLUSIONS: The young men who attended the outreach clinic were
      happy to undergo both non-invasive urine based testing for gonorrhoea and
      chlamydia as well as phlebotomy to test for HIV and syphilis. The 374 clinic
      approach may prove to be a useful model for further outreach services to combat
      poor sexual health of young men in inner city areas.

PMID- 15572620
TI  - Can mainstream services learn from male only sexual health pilot projects?
AB  - Over the past decade a number of community based sexual health projects aimed
      solely at young men have proved to be very successful at attracting young men
      into genitourinary medicine services. These projects are often short term funded
      and under evaluated so it isn't clear exactly how successful they are and why
      this might be so. These projects should be carefully evaluated and examined to
      elicit factors, either unique or common in nature, which could be utilised by
      mainstream sexual health services wishing to develop work with young men. There
      are many barriers to this happening in mainstream services, some being resource
      and time problems and others to do with values of staff and lack of quality
      training. The article looks at practical ways that working with men and the
      skills and confidence of staff can be improved in mainstream settings while
      recognising that much of what needs to be done to support the needs of young men
      must take place in the planning and commissioning stage of services.

PMID- 15572621
TI  - Differences in demographics and risk factors among men attending public v non
      public STD clinics in Baltimore, Maryland.
AB  - OBJECTIVE: To compare the demographics and risk factors of men who utilise the
      services of a municipal public sexually transmitted disease (STD) clinic with
      those who utilise the services provided by a non-public men's STD clinic operated
      by a not for profit primary care clinic. METHODS: A record based review of the
      characteristics and STD prevalence of men who visited a non-public STD clinic in
      Baltimore, Maryland, compared with those of a random sample of male attendees of
      a public STD clinic. Data abstracted from the records included information on
      age, race/ethnicity, self reported risk behaviours, and STD tests and results. We
      used chi2 analysis as well as bivariate and multivariate modelling to compare
      differences in categorical factors between clinics groups. RESULTS: Men who
      utilised the services at the non-public STD clinic were more often white (71% v
      3%, p<0.001), MSM (65% v 2%, p<0.001), and presented for general screening (52% v
      15%, p<0.001) compared to those at the public clinic. In addition, they more
      frequently reported > or =3 partners (22% v 11%, p=0.005), and having an HIV
      positive partner (10% v 3%, p=0.005). Factors independently associated with
      attendance at non-public clinic in multivariate analysis were general screening
      as reason for visit (OR = 11.0, p<0.001), having 3+ partners in past month
      (OR=10.5, p=0.002), and "sometimes" using condoms (OR=3.6, p=0.033). CONCLUSIONS:
      Non-public STD clinics can reach a distinct segment of the male population with
      high risk sexual behaviours that might not attend public STD clinics.

PMID- 15572622
TI  - Recent trends in diagnoses of HIV and other sexually transmitted infections in
      England and Wales among men who have sex with men.
AB  - OBJECTIVES: To examine trends in rates of diagnoses of HIV and other sexually
      transmitted infections (STIs) in men who have sex with men (MSM) in England and
      Wales between 1997 and 2002. METHODS: Estimates of the MSM population living in
      England and Wales, London and the rest of England and Wales were applied to
      surveillance data, providing rates of diagnoses of HIV and STIs and age group
      specific rates for HIV and uncomplicated gonorrhoea. RESULTS: Between 1997 and
      2002, rates of diagnoses of HIV and acute STIs in MSM increased substantially.
      Rates in London were higher than elsewhere. Rises in acute STIs were similar
      throughout England and Wales, except for uncomplicated gonorrhoea and infectious
      syphilis, with greater increases outside London. Rates of gonorrhoea diagnoses
      doubled between 1999 and 2001 (661/100,000, 1271/100,000, p<0.001) in England and
      Wales followed by a slight decline to 1210/100,000 (p=0.03) in 2002-primarily the
      result of a decline in diagnoses among men aged 25-34 (1340/100,000,
      1128/100,000, p<0.001) and 35-44 (924/100,000, 863/100,000, p=0.03) in London.
      HIV was the third most common STI diagnosed in MSM in England and Wales and the
      second in London, with the highest rate (1286/100,000) found among men aged 35-44
      in London in 2002. CONCLUSIONS: Rates of diagnosis of HIV and other STIs have
      increased substantially among MSM in England and Wales. Increases show
      heterogeneity by infection, geography, and age over time. Rates in London were
      twice those seen elsewhere, with greatest changes over time. The observed changes
      reflect concomitant increases in high risk behaviour documented in behavioural
      surveillance survey programmes.

PMID- 15572623
TI  - Seroprevalence of and risk factors for HIV-1 infection among South American men
      who have sex with men.
AB  - OBJECTIVES: Sex among men constitutes an important route of transmission for HIV
      type 1 (HIV-1) in Latin America. Seeking better understanding of risk behaviours
      in this region, we determined the seroprevalence, potential risk factors, and
      geographic distribution of HIV-1 among groups of men who have sex with men (MSM).
      METHODS: Seroepidemiological, cross sectional studies of 13,847 MSM were
      conducted in seven countries of South America during the years 1999-2002.
      Volunteers were recruited in city venues and streets where anonymous
      questionnaires and blood samples were obtained. HIV-1 infection was determined by
      enzyme linked immunosorbent assay (ELISA) screening and western blot (WB)
      confirmatory tests. RESULTS: HIV-1 seroprevalence varied widely (overall 12.3%,
      range 11.0%-20.6%). The highest HIV-1 seroprevalence was noted in Bolivia (20.6%)
      and the lowest in Peru (11.0%). Predictors of HIV-1 infection varied among
      countries; however, a history of previous sexually transmitted disease (STD) was
      associated with a consistent increased risk (ORs=1.9-2.9, AORs=1.8-2.7). Multiple
      weekly sexual contacts was found to represent a secondary risk factor in Ecuador,
      Peru, and Argentina (ORs=1.6-2.9, AORs=1.6-3.1), whereas use of drugs such as
      cocaine was found to increase risk in Bolivia, Uruguay, and Paraguay (ORs=2.5
      6.5, AORs=2.6-6.1). CONCLUSION: The results of this study illustrate an elevated
      HIV-1 seroprevalence among MSM participants from Andean countries. A previous STD
      history and multiple partners predicted HIV-1 infection in the seven countries of
      South America. In Southern Cone countries, HIV-1 infection was also associated
      with use of illegal drugs such as cocaine.

PMID- 15572624
TI  - Screening for syphilis among men who have sex with men in various clinical
      settings.
AB  - OBJECTIVES: To assess the prevalence of syphilis infections among men who have
      sex with men (MSM) accessing the Brisbane Sexual Health Clinic during the period
      1997 up to May 2003, data were collated through three clinical programmes
      conducted by the service-a large inner city mainstream sexual health clinic and
      two small outreach sessional clinics conducted on the site of male sex on
      premises venues (SOPV). Data analysis also provided the opportunity to evaluate
      the effectiveness of the smaller outreach clinics to access populations of MSM
      less likely to attend or identify at the larger mainstream clinic, and therefore
      enhance the detection of previously undiagnosed sexually transmissible
      infections. METHODS: Computerised records from 1997-2003 were collated for a
      statistical analysis of syphilis and other STI pathology results for all MSM
      accessing the mainstream clinic, and two outreach clinics. RESULTS: A review of
      client charts showed that 16 new syphilis diagnoses were made over the previous 5
      years, but only two of these infections (both through the mainstream clinic) were
      early syphilis and therefore transmissible. All other cases were latent
      infections. A higher proportion of bisexual men was identified with positive
      syphilis serology but this was just below significance (p=0.06). Significantly,
      almost a third of syphilis diagnoses (all latent) were made at SOPV outreach
      clinics, despite the much lower proportion of clients seen overall through the
      SOPV clinics. For other sexually transmissible infections, the mainstream clinic
      demonstrated greater efficiency at case detection. CONCLUSION: Outreach clinics
      located in male saunas may serve an effective function in syphilis screening by
      facilitating access for a particular subpopulation of MSM (bisexual, married
      men). These outreach clinics may provide important outlets for education and
      opportunistic screening of asymptomatic MSM and foster a greater willingness for
      men to honestly self identify. However, larger, mainstream clinics serve a more
      anonymous venue for the testing of symptomatic men.

PMID- 15572625
TI  - Lessons from the syphilis outbreak in homosexual men in east London.
AB  - OBJECTIVES: To describe the epidemiology, presentation, and diagnosis of early
      syphilis in 103 homosexual men in east London. METHODS: A retrospective study
      using data from KC60 returns, the Health Protection Agency (HPA) enhanced
      surveillance forms and case notes. RESULTS: 40 cases of primary (PS), 40 of
      secondary (SS) and 23 of early latent syphilis were identified, 33% co-infected
      with HIV. 41% had concurrent sexually transmitted infections (STIs). Pain
      featured in 35% of PS and itch in 13% of rashes. Dark ground microscopy (DGM),
      performed in 44 of the symptomatic cases, was positive in 37 (84%) allowing early
      management. Initial syphilis serology was negative in 15/40 (37%) cases of PS.
      51% and 49% opted for parenteral and oral treatment, respectively. In 53/103
      (51%) cases oral sex was the only risk factor. 86% of infections were UK
      acquired. Only 4% of contacts were seen. CONCLUSION: This outbreak, reflecting
      the resurgence of syphilis across the United Kingdom, highlights several
      important points. Painful chancres and itchy rash are common presentations. DGM
      is a highly sensitive diagnostic tool. Initial negative serological screening
      tests are common in PS and sero-surveillance for 3 months is recommended. The
      high prevalence of concomitant STIs indicates ongoing unprotected sexual
      intercourse. Oral sex is a significant risk factor and is a distinctly "unsafe"
      practice. Conventional partner notification is ineffective. Other methods of
      screening of the at-risk homosexual population are warranted. Continued education
      is required to reduce STI acquisition in homosexual men.

PMID- 15572626
TI  - Don't ask, don't tell: patterns of HIV disclosure among HIV positive men who have
      sex with men with recent STI practising high risk behaviour in Los Angeles and
      Seattle.
AB  - OBJECTIVES: A high incidence of HIV continues among men who have sex with men
      (MSM) in industrialised nations and research indicates many MSM do not disclose
      their HIV status to sex partners. Themes as to why MSM attending sexually
      transmitted infection (STI) clinics in Los Angeles and Seattle do and do not
      disclose their HIV status are identified. METHODS: 55 HIV positive MSM (24 in
      Seattle, 31 in Los Angeles) reporting recent STI or unprotected anal intercourse
      with a serostatus negative or unknown partner from STI clinics underwent in-depth
      interviews about their disclosure practices that were tape recorded, transcribed
      verbatim, coded, and content analysed. RESULTS: HIV disclosure themes fell into a
      continuum from unlikely to likely. Themes for "unlikely to disclose" were HIV is
      "nobody's business," being in denial, having a low viral load, fear of rejection,
      "it's just sex," using drugs, and sex in public places. Themes for "possible
      disclosure" were type of sex practised and partners asking/disclosing first.
      Themes for "likely to disclose" were feelings for partner, feeling responsible
      for partner's health, and fearing arrest. Many reported non-verbal disclosure
      methods. Some thought partners should ask for HIV status; many assumed if not
      asked then their partner must be positive. CONCLUSIONS: HIV positive MSM's
      decision to disclose their HIV status to sex partners is complex, and is
      influenced by a sense of responsibility to partners, acceptance of being HIV
      positive, the perceived transmission risk, and the context and meaning of sex.
      Efforts to promote disclosure will need to address these complex issues.

PMID- 15572627
TI  - HIV status of sexual partners is more important than antiretroviral treatment
      related perceptions for risk taking by HIV positive MSM in Montreal, Canada.
AB  - OBJECTIVE: To examine the role of antiretroviral treatment related perceptions
      relative to other clinical and psychosocial factors associated with sexual risk
      taking in HIV positive men who have sex with men (MSM). METHODS: Participants
      were recruited from ambulatory HIV clinics in Montreal. Information on
      sociodemographic factors, health status, antiretroviral treatment related
      perceptions, and sexual behaviours was collected using a self administered
      questionnaire. At-risk sexual behaviour was defined as at least one occurrence of
      unprotected insertive or receptive anal intercourse in the past 6 months.
      Multivariate logistic regression was performed to evaluate the associations
      between at-risk sexual behaviour and covariates. RESULTS: 346 subjects
      participated in the study. Overall, 34% of subjects were considered at risk; 43%
      of sexually active subjects (n=274). At-risk sexual behaviour was associated with
      two antiretroviral treatment related perceptions: (1) taking antiretroviral
      treatment reduces the risk of transmitting HIV (adjusted odds ratio (OR), 2.10;
      95% confidence interval (CI), 1.16 to 3.80); and (2) there is less safer sex
      practised by MSM because of HIV treatment advances (OR, 1.82; CI, 1.14 to 2.90).
      Other factors, however, were more strongly associated with risk. These were: (1)
      safer sex fatigue (OR, 3.23; CI, 1.81 to 5.78); (2) use of "poppers" during
      sexual intercourse (OR, 6.28; CI, 2.43 to 16.21); and (3) reporting a greater
      proportion of HIV positive anal sex partners, compared with reporting no HIV
      positive anal sex partners: (a) <50% HIV positive (OR, 16.79; CI, 4.70 to 59.98);
      (b) > or =50% HIV positive (OR, 67.67; CI, 15.43 to 296.90). CONCLUSION: Despite
      much emphasis on HIV treatment related beliefs as an explanation for sexual risk
      taking in MSM, this concern may play a relatively minor part in the negotiation
      of risk by HIV positive MSM. Serosorting, safer sex fatigue, and the use of
      poppers appear to be more important considerations in understanding the sexual
      risk behaviours of HIV positive MSM.

PMID- 15572628
TI  - Risk of undiagnosed infection in men attending a sexual assault referral centre.
AB  - OBJECTIVES: To investigate men undergoing forensic examination at the Haven, a
      specialist centre for the management of sexual assault in south London. METHODS:
      Forensic notes of 92 men attending the Haven from May 2000 to August 2003 were
      identified and a detailed review performed. RESULTS: Males ranged in age from 12
      to 51 years, with 83% within the range 12-35 years. 78% were white. Of those who
      were sexually active (n=82) 30% were heterosexual, 34% were homosexual, and the
      remainder provided no information regarding sexual orientation. Most clients were
      referred by the police (n=79) and attended within 3 days of the alleged assault
      (n=73). Many of the victims had increased vulnerability to assault-for example,
      through alcohol or drug consumption or mental health difficulties. One assailant
      was reported in 61 cases but two or more assailants in 26. Women were reported as
      assailants in four cases. The sexual assault was frequently accompanied by other
      physical assault (n=45). Use/threat of a weapon was reported in 18 cases. Rape or
      attempted rape was reported in 59 cases and was the most common assault. Non
      genital injuries were documented in 37 men (40%). Anal injuries were seen in 31
      (34%). The non-attendance rate at follow up was 41%. Post-exposure prophylaxis
      (PEP) against HIV was commenced in 31 men (34%). 23 of the 54 men (43%) reporting
      rape and 14 of the 31 (45%) with anal injuries initiated PEP. CONCLUSIONS: The
      number of men presenting after sexual assault is likely to increase but despite
      significant risk many do not engage with medical care. This carries an unknown
      risk of HIV and other STI transmission.

PMID- 15572629
TI  - HIV risk profile of male street youth involved in survival sex.
AB  - OBJECTIVES: To compare HIV risk factors of male street youth involved in survival
      sex with those of their never involved peers and to describe the sexual
      activities of the involved youths. METHODS: From 2001 to 2003, street youth aged
      14-23 years were recruited from street youth agencies in Montreal, Canada.
      Information was collected on sociodemographic characteristics, substance use, and
      sexual behaviours. Involvement in survival sex was defined as having ever
      exchanged sex for money, gifts, drugs, shelter, or other needs. Logistic
      regression was used to identify HIV risk factors associated with involvement in
      survival sex. RESULTS: Among the 542 male participants recruited, 27.7% reported
      involvement in survival sex. HIV risk factors independently associated with such
      involvement were injection drug using partners (modulated by length of
      homelessness), unprotected oral sex with male partners, steroid injection,
      history of sexual abuse, and drug injection. Among involved youths, 32.0% had
      only female clients, 41.3% only male clients, and 26.7% had clients of both
      sexes. Unprotected sexual activities were common with clients. However, even more
      risks were taken with non-commercial sexual partners. CONCLUSIONS: Male street
      youth involved in survival sex are at higher risk for HIV than their non-involved
      peers not only because of their unprotected commercial sexual activities. They
      have multiple other HIV risks related to non-commercial sexual activities, drug
      injection, and sexual abuse. All these risks need to be addressed when providing
      sexual health interventions for this population.

PMID- 15572630
TI  - Factors associated with sex trade involvement among male participants in a
      prospective study of injection drug users.
AB  - OBJECTIVES: While much research to date has examined female sex trade work,
      little has been done to evaluate factors associated with male sex trade
      involvement or to assess their health service needs. This is particularly true
      for male sex trade workers who are also injection drug users (IDUs). Therefore,
      the present analyses were undertaken to evaluate factors associated with sex
      trade work in a prospective cohort study of male IDUs. METHODS: We identified
      factors associated with sex trade involvement among male participants enrolled in
      the Vancouver Injection Drug Users Study (VIDUS). Since serial measures for each
      individual were available at semiannual intervals, variables potentially
      associated with sex trade involvement were evaluated with adjusted odds ratios
      (AOR) and 95% confidence intervals (CI) computed using generalised estimating
      equations (GEE). RESULTS: Between 1996 and 2003, 995 male IDUs were enrolled into
      the VIDUS cohort among whom 108 (11%) reported being involved in the sex trade at
      enrolment and 102 (10%) individuals initiated sex trade involvement during the
      follow up period. In multivariate analyses, factors independently associated with
      sex trade involvement included HIV positive serostatus (AOR: 1.77 (95% CI: 1.44
      to 2.17)), daily cocaine injection (AOR: 1.37 (95% CI: 1.11 to 1.70)), daily
      crack smoking (AOR: 1.36 (95% CI: 1.07 to 1.72)), borrowing syringes (AOR: 1.73
      (95% CI: 1.32 to 2.25)), and inconsistent use of condoms with casual sexual
      partners (AOR 0.66, CI 0.53 to 0.82). We also found that male sex trade workers
      were more likely to report having sought but been unable to access substance
      abuse treatment (AOR: 1.28 (95% CI: 0.98 to 1.67); p=0.076). CONCLUSIONS: Males
      involved in the sex trade in this setting have higher levels of HIV infection and
      engage in risky injection behaviours at an elevated rate. Since these behaviours
      have major implications for HIV acquisition and public health, prevention efforts
      and targeted provision of addiction treatment to this population should be
      expanded.

PMID- 15572631
TI  - HIV, syphilis infection, and sexual practices among transgenders, male sex
      workers, and other men who have sex with men in Jakarta, Indonesia.
AB  - OBJECTIVES: To establish the prevalence of HIV, syphilis, and sexual risk
      behaviour among three groups of men who have sex with men in Jakarta, Indonesia,
      and to investigate sexual links between these men and broader heterosexual
      populations. METHODS: Anonymous, cross sectional surveys among community
      recruited transgender and male sex workers and self recognised men who have sex
      with men (MSM) were undertaken in mid-2002 in Jakarta, Indonesia. Places where
      transgender and male sex workers sell sex and where men go to meet non-commercial
      male sex partners were mapped. Probability samples were selected for the sex
      worker populations, while a mixed probability and convenience sample was drawn
      for self recognised MSM. Blood was drawn for HIV and syphilis serology and
      community interviewers administered a standardised questionnaire. RESULTS: HIV
      prevalence was 22% among transgender sex workers, 3.6% among male sex workers,
      and 2.5% among self recognised MSM, and syphilis prevalence was 19.3%, 2.0% and
      1.1% respectively. 59.3% of transgender sex workers and 64.8% of male sex workers
      reported recent unprotected anal intercourse with clients, and 53.1% of other MSM
      reported unprotected anal sex with male partners. Some 54.4% of male sex workers
      and 18.3% of other MSM reported female partners in the preceding year.
      CONCLUSION: HIV has reached substantial levels among transgender sex workers, and
      is not negligible in other MSM groups. Risk behaviour is high in all
      subpopulations, and bisexual behaviour is common, meaning the threat of a wider
      epidemic is substantial. Prevention programmes targeting male-male sex are needed
      to reduce this threat.

PMID- 15572632
TI  - Changes in regular condom use among immigrant transsexuals attending a
      counselling and testing reference site in central Rome: a 12 year study.
AB  - OBJECTIVE: To analyse data from male to female transsexuals attending between
      1992 and 2003 an outpatient clinic considered the main HIV counselling and
      testing site in Rome for foreign people. METHODS: Data collected between 1992 and
      2003, from a routine anti-HIV testing and counselling activity, were analysed. A
      brief standard interview was performed at each test. A cross sectional analysis
      to assess the association of regular condom use with demographic and behavioural
      variables using multiple logistic regression was performed. A follow up analysis
      to define the effect of single factors on the occurrence of new anti-HIV
      seroconversions was also performed. The incidence of anti-HIV seroconversion was
      calculated in person years of observation. RESULTS: Overall, 473 transsexuals sex
      workers were tested. Most of them (99%) were from South America (mainly Columbia
      and Brazil). Anti-HIV prevalence was 32%, but a progressive decrease over time
      was observed (from 57% in 1993 to 12% in 2003). The proportion of patients
      reporting regular condom use at enrolment was 75%. A progressive increase in
      regular condom use was reported over time (from 43% in 1992-3 to 79% in 2002-3).
      15 new HIV infections were observed during follow up (incidence 2.1 per 100
      person years). Though the proportion of patients reporting regular condom use
      increased over time, 10 out of the 15 new infections occurred in patients
      reporting unprotected sex during follow up (rate 8.4 per 100 person years).
      CONCLUSIONS: Our data suggest that counselling may lead to an increase in safe
      sex practices among immigrant transsexuals. However, the incidence of new HIV
      infections is still high and mainly related to non-regular condom use, which
      still remains the primary objective of prevention.

PMID- 15572633
TI  - Penile injection of foreign bodies in eight Thai patients.

PMID- 15572634
TI  - Monitoring sexual behaviour in general populations: a synthesis of lessons of the
      past decade.
AB  - This supplement contains selected papers from a workshop on the measurement of
      sexual behaviour in the era of HIV/AIDS held at the London School of Hygiene and
      Tropical Medicine in September 2003. The focus was on low and middle income
      countries, where the majority of HIV infections occur. The motive for holding
      such a meeting is easy to discern. As the AIDS pandemic continues to spread and
      as prevention programmes are scaling up, the need to monitor trends in sexual
      risk behaviours becomes ever more pressing. Behavioural data are an essential
      complement to biological evidence of changes in HIV prevalence or incidence.
      Biological evidence, though indispensable, is by itself insufficient for policy
      and programme guidance. AIDS control programmes need to be based on monitoring of
      not only trends in infections but also of trends in those behaviours that
      underlie epidemic curtailment or further spread.

PMID- 15572635
TI  - A critique of international indicators of sexual risk behaviour.
AB  - OBJECTIVES: To investigate whether the indicators of sexual risk behaviour,
      defined by UNAIDS for use among members of general populations, have been found
      as risk factors, to examine how information on sexual behaviour is collected and
      summarised in order to calculate the indicators, and to look for possible sources
      of error in the data and in interpretation of those indicators. METHODS: The
      literature on risk factors for HIV infection was reviewed. Indicators were
      calculated for countries where data were available for two or more points in
      time. RESULTS: Indicators of sexual behaviour describe behaviours that are
      relevant to HIV risk and that are amenable to change. These behaviours do not
      correspond closely to the individual risk factors for HIV infection that have
      been identified in observational studies. CONCLUSIONS: Although potential errors
      of both measurement and interpretation exist, most of the indicators currently
      defined can fulfil their purpose, providing they are used with caution. Many of
      the indicators should not be interpreted in isolation but need supporting
      information to make sense of trends or differences between groups. Much of this
      information is provided by other indicators. The source of the data used to
      calculate the indicator is potentially important and should always be provided
      with indicator estimates. Some estimate of the accuracy of the estimate, either
      by means of confidence intervals or the number of respondents, should be given.

PMID- 15572636
TI  - Measuring sexual behaviour in the era of HIV/AIDS: the experience of Demographic
      and Health Surveys and similar enquiries.
AB  - OBJECTIVES: To review the sexual behaviour data collected in the Demographic and
      Health Surveys (DHS) and other similar national surveys from the perspective of
      data quality. METHODS: Two indicators of premarital and higher risk sexual
      behaviour were analysed for 31 surveys in 10 countries in sub-Saharan Africa and
      Latin America and the Caribbean. The analysis focused on the internal consistency
      of trends and gender differences in the reported indicators. RESULTS: The authors
      found fluctuating trends in premarital sex in sub-Saharan Africa but consistent
      increases in Latin America and the Caribbean. Changes in questionnaire design do
      not seem to contribute to these trends and there is evidence that the increase in
      premarital sex is genuine in Latin America. Trends in sex with non-spousal, non
      cohabiting partners show large fluctuations and inconsistencies between surveys
      in some countries but not others. Men are consistently more likely to report non
      marital sexual partners than women and unmarried women are less likely than
      unmarried men to report casual partners. CONCLUSIONS: Surveys are potentially a
      valuable source of information on sexual behaviour but there are sufficient
      grounds for concern to warrant considerable caution in the use of survey data to
      monitor trends in sexual behaviour. Survey findings must be evaluated carefully
      and interpreted in the context of other available information. These results
      caution against placing heavy emphasis on short term changes in sexual behaviour
      between individual surveys and highlight the need for attention to quality in
      data collection.

PMID- 15572637
TI  - Age at first sex: understanding recent trends in African demographic surveys.
AB  - OBJECTIVES: To describe recent trends in age at first sex in African countries,
      identifying and making due allowances for a variety of common reporting errors.
      METHODS: Demographic and Health Surveys (DHS) data from six African countries
      conducting three or more surveys since 1985 were analysed using survival analysis
      techniques, combining information on virginity status and retrospective reporting
      of age at first sex. Hazard analysis was used to separate the effects of
      reporting error and compositional change and to estimate true changes in sexual
      debut over time. A multistate life table analysis incorporating transition to
      first marriage allowed cohorts to be classified according to person years spent
      as virgins, as sexually active unmarried, and married. RESULTS: Intersurvey
      comparisons generally suggested a slow secular rise in age at first sex. However,
      tracing birth cohorts between surveys revealed inconsistencies--median ages
      reported by female members of a birth cohort in their teens were generally higher
      than those reported when they reached their twenties, even when allowing for
      residence and education changes--probably a result of young, sexually active
      women denying they had ever had sex. Male birth cohorts tend to display the
      opposite kind of bias. CONCLUSIONS: Uganda, Kenya, and Ghana have experienced a
      more pronounced and unambiguous decline in premarital sexual activity than
      Tanzania, Zambia, and Zimbabwe, with statistically significant increases in age
      at first sex. In addition, Uganda has maintained a very short interval between
      onset of sexual activity and marriage for both sexes.

PMID- 15572638
TI  - Informal confidential voting interview methods and temporal changes in reported
      sexual risk behaviour for HIV transmission in sub-Saharan Africa.
AB  - OBJECTIVES: Reliable data on sexual behaviour trends are needed to evaluate HIV
      interventions in sub-Saharan Africa but are difficult to obtain due inter alia to
      social desirability bias. The objective of this paper is to assess whether the
      use of informal confidential voting interviews (ICVI) was associated with greater
      reporting of socially proscribed behavioural risk factors for HIV infection than
      were conventional interviewing methods. METHODS: Comparison of changes in reports
      of risk behaviours for HIV infection in ICVI versus face to face interviews
      (FTFIs) between the first two rounds of a large scale, longitudinal, population
      based survey in Manicaland, Zimbabwe. Examination of factors that could
      contribute to observed changes in the effect of ICVI, including temporal changes
      in response error and social desirability, and factors affecting statistical
      power to detect differences between methods-that is, reductions in the prevalence
      of risk behaviours and sample size. RESULTS: Enhanced reporting of HIV associated
      risk behaviours in ICVI interviews was not so apparent in the second round as in
      the first round of the survey, particularly for less frequently reported
      behaviours. Levels of reported HIV associated risk behaviour and sample sizes
      both declined between the two survey rounds. The level of response error was
      higher in ICVI interviews than in FTFI interviews but did not alter over time.
      CONCLUSION: ICVI interviews can reduce social desirability bias in data on HIV
      associated risk behaviours. The extent and direction of change in net reduction
      in bias over time remains uncertain and will depend on local circumstances.

PMID- 15572639
TI  - Consistency in the reporting of sexual behaviour by adolescent girls in Kenya: a
      comparison of interviewing methods.
AB  - OBJECTIVES: To investigate in a district in Kenya the level and consistency of
      reporting of sexual behaviour among adolescent girls randomly assigned to two
      modes of survey interview: face to face interview and audio computer assisted
      self-interview (ACASI). METHODS: The analysis is based on a subsample of over 700
      never married girls aged 15-21 years in Kisumu, Kenya, drawn from a population
      based survey of over 2100 respondents. A questionnaire with 69 questions was
      used, two thirds of which were considered sensitive, including questions about
      risky sexual behaviour, alcohol and drug use, contraceptive practice, pregnancy,
      induced abortions, and births. RESULTS: ACASI produced significantly higher
      reporting of sex with a relative, stranger, or older man, and higher reporting of
      coerced sex. However, differences by mode for ever had sex and sex with a
      boyfriend were not significant. Relative to ACASI, the interviewer administered
      mode produced highly consistent reporting of sexual activity, both within the
      main interview and between the main and exit interviews. CONCLUSIONS: Both the
      mode of survey administration and the probing for various behaviours
      significantly affect the observed prevalence of sexual activity. The ACASI
      results suggest that adolescent girls in Kenya have more complex and perilous sex
      lives than traditional face to face surveys of sexual activity indicate. The
      level of consistency in the interviewer mode is argued to be suspect,
      particularly given the much lower levels of reporting, relative to ACASI, for
      types of sexual partners and coerced sexual activity.

PMID- 15572640
TI  - "A bit more truthful": the validity of adolescent sexual behaviour data collected
      in rural northern Tanzania using five methods.
AB  - OBJECTIVE: To assess the validity of sexual behaviour data collected from African
      adolescents using five methods. METHODS: 9280 Tanzanian adolescents participated
      in a biological marker and face to face questionnaire survey and 6079 in an
      assisted self-completion questionnaire survey; 74 participated in in-depth
      interviews and 56 person weeks of participant observation were conducted.
      RESULTS: 38% of males and 59% of females reporting sexual activity did so in only
      one of the two 1998 questionnaires. Only 58% of males and 29% of females with
      biological markers consistently reported sexual activity in both questionnaires.
      Nine of 11 (82%) in-depth interview respondents who had had biological markers
      provided an invalid series of responses about sex in the survey and in-depth
      interview series. Only one of six female in-depth interview respondents with an
      STI reported sex in any of the four surveys, but five reported it in the in-depth
      interviews. CONCLUSION: In this low prevalence population, biological markers on
      their own revealed that a few adolescents had had sex, but in combination with in
      depth interviews they may be useful in identifying risk factors for STIs. Self
      reported sexual behaviour data were fraught with inconsistencies. In-depth
      interviews seem to be more effective than assisted self-completion questionnaires
      and face to face questionnaires in promoting honest responses among females with
      STIs. Participant observation was the most useful method for understanding the
      nature, complexity, and extent of sexual behaviour.

PMID- 15572641
TI  - Surveillance and modelling of HIV, STI, and risk behaviours in concentrated HIV
      epidemics.
AB  - BACKGROUND: HIV epidemics in most countries are highly concentrated among
      population subgroups such as female sex workers, injecting drug users, men who
      have sex with men, mobile populations, and their sexual partners. The perception
      that they are important only when they cause epidemic expansion to general
      populations has obscured a critical lack of coverage of preventive interventions
      in these groups, as well as appropriate methods for monitoring epidemic and
      behavioural risk trends. The difficulties in accessing such groups have likewise
      often cast doubt on the representativeness of observed disease and behavioural
      risk estimates and their validity and reliability, particularly those related to
      sampling and the measurement of risk behaviours. OBJECTIVES: To review
      methodological obstacles in conducting surveillance with population subgroups in
      concentrated HIV epidemics, elaborate on recent advancements that partially
      overcome these obstacles, and illustrate the importance of modelling integrated
      HIV, STI, and behavioural surveillance data. METHODS: Review of published HIV,
      STI, and behavioural surveillance data, research on epidemic dynamics, and case
      studies from selected countries. CONCLUSIONS: The population subgroups that merit
      regular and systematic surveillance in concentrated epidemics are best determined
      through extensive assessment and careful definition. Adherence to recently
      refined chain referral and time location sampling methods can help to ensure more
      representative samples. Finally, because of the inherent limitations of cross
      sectional surveys in understanding associations between complex sexual behaviours
      and HIV and STI transmission, mathematical models using multiple year data offer
      opportunities for integrated analysis of behavioural change and HIV/STI trends.

PMID- 15572642
TI  - Where the action is: monitoring local trends in sexual behaviour.
AB  - OBJECTIVES: To assess the role in an overall monitoring strategy of the PLACE
      method of estimating local trends in sexual behaviour among individuals at social
      venues in areas at increased risk of HIV transmission. METHODS: Public venues
      identified by community informants as places where people meet new sexual
      partners were visited and characterised in Karaganda, Kazakhstan, in 2002 and
      2003, and in a township in South Africa in 2000 and 2003. At a subset of venues,
      a representative sample of individuals socialising at the venue were interviewed
      about their sexual behaviour. The age distribution and partnerships rates of
      those socialising at these venues were compared by year and with national data
      from Kazakhstan and South Africa obtained via household surveys. RESULTS: Women
      and men socialising at venues were younger and had higher rates of new and
      concurrent partnerships than men and women interviewed in national household
      surveys. There was little apparent change in sexual behaviour between 2002 and
      2003 in Karaganda. In the South African township, there was a reduction in sexual
      partnerships and an increase in condom use, possibly due to a local AIDS
      prevention programme. CONCLUSION: Findings from the PLACE method supplement
      national data on sexual behaviours with data from key populations in high
      transmission areas, inform local targeting of interventions, and, when subsequent
      rounds of PLACE are implemented, can evaluate change in target populations.

PMID- 15572643
TI  - Methodological lessons from a cohort study of high risk women in Tanzania.
AB  - OBJECTIVES: To describe the development, characteristics, and follow up of a high
      risk cohort of women in Tanzania. Differences in social background and sexual
      behaviour of women working in traditional and modern alcohol selling workplaces
      are shown. METHODS: Data from questionnaires four months before the enrollment of
      the cohort, at enrollment, and at 32 months were compared. Key informant
      interviews, social mapping exercises, and focus group discussions were held
      before the start of the cohort. RESULTS: In the absence of organised
      prostitution, two different groups of women with high risk exposure were
      identified during the baseline survey: female workers in modern alcohol selling
      places such as bars, guesthouses, and restaurants (barmaids) and in traditional
      places (local brew sellers). Overall, the population had a mean age of 27.7 years
      with barmaids tending to be younger (24.3 years) than local brew sellers (34.2
      years). The main duration of stay in the current workplace was 2.1 years
      (barmaids 0.9 years; local brew sellers 4.1 years). Barmaids were more likely to
      have paying casual sex partners than local brew sellers and used condoms more
      regularly. Local brew sellers tend to be more stable with only 10% lost to follow
      up after 32 months compared with 24.4% of the bar workers. CONCLUSIONS:
      Preliminary work revealed major differences in characteristics and behaviour
      between women working in modern and traditional alcohol selling outlets. Thorough
      preparation of the study, close monitoring of the cohort, and provision of
      selected benefits resulted in high retention rates over a 32 month project in a
      highly mobile population.

PMID- 15572644
TI  - Trends in sexual behaviours and infections among young people in the United
      States.
AB  - OBJECTIVES: To describe trends over time in sexual behaviour, condom use, and
      sexually transmitted infections among female and male adolescents in the United
      States. METHODS: A review was carried out of published studies using data from
      six surveys since the 1970s on sexual behaviour and surveillance data on sexually
      transmitted infections. RESULTS: The proportion of adolescents who have ever had
      sexual intercourse increased for females and males through the 1980s and then
      declined for males through the 1990s. Some survey data showed that the level
      remained unchanged in the 1990s for adolescent females and other sources showed a
      decline by 2001. Condom use at first sexual intercourse and current condom use
      have increased over the past two decades for both male and female adolescents.
      Incidence rates for gonorrhoea and syphilis among adolescents declined over the
      1990s and up through 2002, though new diagnoses of HIV/AIDS among adolescents
      remained relatively constant throughout the 1990s and into the new century.
      CONCLUSION: Although data sources are difficult to compare over time, trends in
      sexual behaviour, condom use, and sexually transmitted infections among
      adolescents from different data sources display generally similar directions
      towards declines in risk behaviours and outcomes, and increases in protective
      behaviours.

PMID- 15572645
TI  - Sexual risk behaviour and infection: epidemiological considerations.

PMID- 15572646
TI  - Monitoring trends in sexual behaviour and HIV/STIs in Peru: are available data
      sufficient?
AB  - OBJECTIVES: To review and summarise various types of Peruvian evidence on sexual
      behaviour, HIV/STI exposure and risk, and discuss how to increase its usefulness
      for HIV/STI risk trend monitoring in Peru. METHODS: Review HIV sentinel
      surveillance conducted by the Ministry of Health; data from the Demographic and
      Health Surveys (DHS); and academic publications on sexual behaviour in
      combination with biological markers. Changes over time, quality of data, size of
      studies, and intended audience are discussed. RESULTS: Data from HIV sentinel
      surveillance showed very high (8-23%) HIV seroprevalence among men having sex
      with men, but stable, relatively low figures among female sex workers (1%) and
      antenatal clinic patients (under 0.5%). DHS data suggest that single women
      increased their sexual activity throughout the 1990s but did not raise their
      contraceptive use accordingly, resulting in increased early conceptions. The
      contribution of condoms to overall contraceptive protection increased threefold
      in 1992-2000. According to the 1996 survey, men become sexually active 2.5 years
      earlier than women, but marry or cohabit four years later than women; women marry
      or cohabit 1.5-2.5 years after first sex, whereas men take eight years to do so.
      Finally, published studies confirmed dramatic differences in HIV prevalence
      between men who have sex with men and other populations, and also suggested
      patterns of bridging from men to women. CONCLUSIONS: Data available from the
      three sources are numerous, although limitations of each approach reduce their
      monitoring utility: Ministry of Health studies should select better sentinel
      populations and timely process behavioural data. Future demographic surveys
      should incorporate an AIDS risk perspective and include men.

PMID- 15572647
TI  - Monitoring trends in sexual behaviour in Zambia, 1996-2003.
AB  - OBJECTIVES: This paper assesses the evidence of changes in sexual behaviour in
      Zambia, accounting for differences in the composition of survey samples and for
      evidence of changes in reporting bias. It compares the estimates of sexual
      behaviour measures obtained using two different survey methodologies. METHODS:
      Data from five nationally representative household surveys carried out between
      1996 and 2003 were analysed for change in selected sexual behaviours. RESULTS:
      There is some evidence for an increase in men's age at first sex. The proportion
      of people reporting multiple partnerships and not using a condom at last sex has
      declined since 1996. Unprotected sex with non-cohabiting partners is reported
      less frequently in the later surveys. The socioeconomic and demographic
      composition of the survey samples has changed across the years but the declines
      in behaviour remain statistically significant after adjustment for these changes.
      There is evidence of a changing reporting bias over the period of interest, with
      respondents less likely to report a young age at first sex in later surveys.
      CONCLUSIONS: Between 1996 and 2003, reported sexual behaviour has changed in
      Zambia among both men and women. Different survey methods produce significantly
      different estimates of sexual behaviour. This must be taken into account when
      carrying out trend analyses using data from different sources.

PMID- 15572648
TI  - Endogenous interleukin-6 enhances the renal injury, dysfunction, and inflammation
      caused by ischemia/reperfusion.
AB  - Here, we investigate the effects of renal ischemia/reperfusion (I/R) on the
      degree of renal injury, dysfunction, and inflammation in interleukin (IL)-6
      knockout (IL-6(-/-)) mice and mice administered a monoclonal antibody against IL
      6. IL-6(-/-) mice were subjected to bilateral renal artery occlusion (30 min) and
      reperfusion (24 h). At the end of experiments, indicators and markers of renal
      dysfunction, injury, and inflammation were measured. Kidneys were used for
      histological evaluation of renal injury. Renal expression of the adhesion
      molecules intercellular adhesion molecule-1 (ICAM-1) and P-selectin, as well as
      nitration of proteins in the kidney, were determined using immunohistochemistry.
      In addition, wild-type mice were pretreated (24 and 1 h before ischemia) with an
      IL-6 antibody to mimic the effects that would be seen in IL-6(-/-) mice. IL-6(-/
      ) mice and wild-type mice administered the IL-6 antibody demonstrated
      significantly reduced plasma urea and creatinine levels, indicating reduction of
      renal dysfunction caused by I/R. Neutrophil infiltration was also significantly
      reduced in IL-6(-/-) mice and wild-type mice administered the IL-6 antibody
      subjected to renal I/R. Proinflammatory cytokines (tumor necrosis factor-alpha
      and IL-1beta) in renal tissues were significantly attenuated in IL-6(-/-) mice to
      levels seen in wild-type mice. IL-6(-/-) mice demonstrated reduced histological
      evidence of tubular injury and markedly reduced immunohistochemical evidence of
      ICAM-1, P-selectin, and nitrotyrosine when subjected to renal I/R. We propose
      that endogenous IL-6 enhances the degree of renal injury, dysfunction, and
      inflammation caused by I/R of the kidney by promoting the expression of adhesion
      molecules and subsequent oxidative and nitrosative stress.

PMID- 15572649
TI  - Predictive models of CYP3A4 Heteroactivation: in vitro-in vivo scaling and
      pharmacophore modeling.
AB  - Although activation of CYP3A4 is frequently observed in vitro, predictive
      computational-based models and methods for in vitro-in vivo scaling are scarce.
      It has been previously shown that in vitro CYP3A4 heteroactivation of
      carbamazepine (CBZ)-epoxide (ep) formation can be associated with the clinical
      drug interaction between felbatame and CBZ. The previously reported prediction
      methodology is applied here to an additional set of in vitro CYP3A4
      heteroactivators, some exerting this effect at concentrations relevant in vivo.
      The antimalarial artemisinin potently increases CBZ-ep formation by a maximum of
      500% at 300 microM. Testosterone and progesterone activates by a maximum of 1680
      and 920%, respectively, at 150 microM, and quinidine causes a 130% increase at
      300 microM. The predicted maximum in vivo decrease in steady-state concentration
      of carbamazepine (Css(CBZ)) at saturating effector concentrations is 85 to 90%
      for testosterone and progesterone, 75% for artemisinin, and 45% for quinidine.
      The corresponding predicted in vivo increase in Css(CBZ-ep) is 50, 60, 55, and
      30% for artemisinin, testosterone, progesterone, and quinidine, respectively. At
      effector concentrations relevant in vivo, the Css(CBZ) change is predicted to
      </=20% for testosterone, artemisinin, and quinidine and </=10% for progesterone,
      with a concomitant Css(CBZ-ep) increase of 12% for testosterone and </=10% for
      progesterone, artemisinin, and quinidine. Structure-heteroactivation
      relationships were evaluated by generating a pharmacophore. The model includes
      two hydrogen bond acceptor features separated by hydrophobic features. Internal
      predictivity is high, and heteroactivation of an external test set correlate to
      observed in vitro heteroactivation.

PMID- 15572650
TI  - Quantitative and fiber-selective evaluation of dose-dependent nerve blockade by
      intrathecal lidocaine in rats.
AB  - We investigated whether cutaneous stimulus threshold (CST), as determined using a
      Neurometer, could be used for quantitative and differential nerve evaluation of
      reversible and irreversible nerve block following intrathecal lidocaine
      administration in rats. Rats with intrathecal catheters were randomly assigned to
      one of five groups (saline or 2, 5, 10, or 20% lidocaine). Prior to and 4 days
      after drug administration, CST was determined at 5, 250, and 2000 Hz. In the 2%
      lidocaine group, CST from end of lidocaine infusion to recovery from anesthesia
      was also monitored. Skin-clamp testing and gait observation were performed for
      comparison with CST findings. Behavioral examinations revealed persistent sensory
      or motor impairment lasting 4 days in groups receiving >/=5% lidocaine but not in
      the saline and 2% lidocaine groups. With 2% lidocaine, return to baseline CSTs at
      5 and 250 Hz was delayed compared with thresholds at 2000 Hz. Although CSTs in
      the 5% group at 5 and 250 Hz increased significantly, thresholds at 2000 Hz did
      not differ from those in rats administered saline. CSTs with >/=10% lidocaine
      displayed no differences between frequencies. At each frequency, CSTs for rats
      with >/=5% lidocaine increased in a clearly concentration-dependent manner. These
      results suggest that CST testing enables evaluation of the different nerve
      functions for Abeta, Adelta, and C fibers in rats for lidocaine concentrations
      </=5% and allows quantitative assessment of persistent neurological deficit
      induced by lidocaine in rats.

PMID- 15572651
TI  - The cyclooxygenase-2 inhibitor GW406381X [2-(4-ethoxyphenyl)-3-[4
      (methylsulfonyl)phenyl]-pyrazolo[1,5-b]pyridazine] is effective in animal models
      of neuropathic pain and central sensitization.
AB  - The pathogenic form of the cyclooxygenase (COX) enzyme, COX-2, is also
      constitutively present in the spinal cord and has been implicated in chronic pain
      states in rat and man. A number of COX-2 inhibitors, including celecoxib and
      rofecoxib, are already used in man for the treatment of inflammatory pain.
      Preclinically, the dual-acting COX-2 inhibitor, GW406381X [2-(4-ethoxyphenyl)-3
      [4-(methylsulfonyl)phenyl]-pyrazolo[1,5-b]pyridazine, where X denotes the free
      base], is as effective as rofecoxib and celecoxib in the rat established Freund's
      Complete Adjuvant model with an ED(50) of 1.5 mg/kg p.o. compared with 1.0 mg/kg
      p.o. for rofecoxib and 6.6 mg/kg p.o. for celecoxib. However, in contrast to
      celecoxib (5 mg/kg p.o. b.i.d.) and rofecoxib (5 mg/kg p.o. b.i.d.), which were
      without significant effect, GW406381X (5 mg/kg p.o. b.i.d.) fully reversed
      mechanical allodynia in the chronic constriction injury model and reversed
      thermal hyperalgesia in the mouse partial ligation model, both models of
      neuropathic pain. GW406381X, was also effective in a rat model of capsaicin
      induced central sensitization, when given intrathecally (ED(50) = 0.07 mug) and
      after chronic but not acute oral dosing. Celecoxib and rofecoxib had no effect in
      this model. Several hypotheses have been proposed to try to explain these
      differences in efficacy, including central nervous system penetration, enzyme
      kinetics, and potency. The novel finding of effectiveness of GW406381X in these
      models of neuropathic pain/central sensitization, in addition to activity in
      inflammatory pain models and together with its central efficacy, suggests dual
      activity of GW406381X compared with celecoxib and rofecoxib, which may translate
      into greater efficacy in a broader spectrum of pain states in the clinic.

PMID- 15572652
TI  - Real-time assessment of postprandial fat storage in liver and skeletal muscle in
      health and type 2 diabetes.
AB  - Liver and skeletal muscle triglyceride stores are elevated in type 2 diabetes and
      correlate with insulin resistance. As postprandial handling of dietary fat may be
      a critical determinant of tissue triglyceride levels, we quantified postprandial
      fat storage in normal and type 2 diabetes subjects. Healthy volunteers (n = 8)
      and diet-controlled type 2 diabetes subjects (n = 12) were studied using a novel
      13C magnetic resonance spectroscopy protocol to measure the postprandial
      increment in liver and skeletal muscle triglyceride following ingestion of 13C
      labeled fatty acids given with a standard mixed meal. The postprandial increment
      in hepatic triglyceride was rapid in both groups (peak increment controls: +7.3
      +/- 1.5 mmol/l at 6 h, P = 0.002; peak increment diabetics: +10.8 +/- 3.4 mmol/l
      at 4 h, P = 0.009). The mean postprandial incremental AUC of hepatic 13C
      enrichment between the first and second meals (0 and 4 h) was significantly
      higher in the diabetes group (6.1 +/- 1.4 vs. 1.7 +/- 0.6 mmol x l(-1) x h(-1), P
      = 0.019). Postprandial increment in skeletal muscle triglyceride in the control
      group was small compared with the diabetic group, the mean 24-h postprandial
      incremental AUC being 0.2 +/- 0.3 vs. 1.7 +/- 0.4 mmol x l(-1) x h(-1) (P =
      0.009). We conclude that the postprandial uptake of fatty acids by liver and
      skeletal muscle is increased in type 2 diabetes and may underlie the elevated
      tissue triglyceride stores and consequent insulin resistance.

PMID- 15572653
TI  - CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH.
AB  - The response to systemic stress is organized along the hypothalamic-pituitary
      adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation)
      is mediated by epidermal melanocytes (cells of neural crest origin) responsible
      for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC),
      corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can
      produce corticosterone. In the present study, incubation of normal epidermal
      melanocytes with CRH was found to trigger a functional cascade structured
      hierarchically and arranged along the same algorithm as in the HPA axis: CRH
      activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene
      expression and production of ACTH. CRH and ACTH also enhanced production of
      cortisol and corticosterone, and cortisol production was also stimulated by
      progesterone. The chemical identity of the cortisol was confirmed by liquid
      chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass
      spectrometry analyses. POMC gene silencing abolished the stimulatory effect of
      CRH on corticosteroid synthesis, indicating that this is indirect and mediated
      via production of ACTH. Thus the melanocyte response to CRH is highly organized
      along the same functional hierarchy as the HPA axis. This pattern demonstrates
      the fractal nature of the response to stress with similar activation sequence at
      the single-cell and whole body levels.

PMID- 15572654
TI  - Melatonin enhances leptin expression by rat adipocytes in the presence of
      insulin.
AB  - Leptin and melatonin play an important role in the regulation of body mass and
      energy balance. Both hormones show a circadian rhythm, with increasing values at
      night. In addition, melatonin receptors were recently described in adipocytes,
      where leptin is synthesized. Here, we investigated the influence of melatonin and
      its interaction with insulin and dexamethasone on leptin expression. Isolated rat
      adipocytes were incubated with melatonin (1 nM) alone or in combination with
      insulin (5 nM) and/or dexamethasone (7 nM) for 6 h. Melatonin or insulin alone
      did not affect leptin expression, but together they increased it by 120%.
      Dexamethasone increased leptin mRNA content (105%), and this effect was not
      enhanced by melatonin. Simultaneous treatment with the three hormones provoked a
      further increase in leptin release (250%) and leptin mRNA (100%). Melatonin
      prevented the forskolin-induced inhibition (95%) of leptin expression. In
      addition, melatonin's ability to stimulate leptin release (in the presence of
      insulin) was completely blocked by pertussis toxin and luzindole. To gain further
      insight into the molecular basis of melatonin and insulin synergism, the insulin
      signaling pathway was investigated. Melatonin increased the insulin-induced
      insulin receptor-beta tyrosine phosphorylation, which led to an increased serine
      phosphorylation of the downstream convergent protein Akt. We concluded that
      melatonin interacts with insulin and upregulates insulin-stimulated leptin
      expression. These effects are caused by melatonin binding to the pertussis toxin
      sensitive G(i) protein-coupled membrane receptor (MT1 subtype) and the cross talk
      with insulin, since insulin receptor and its convergent target Akt are
      coactivated by melatonin.

PMID- 15572655
TI  - Age diminishes the testicular steroidogenic response to repeated intravenous
      pulses of recombinant human LH during acute GnRH-receptor blockade in healthy
      men.
AB  - Testosterone (Te) concentrations fall gradually in healthy aging men. Postulated
      mechanisms include relative failure of gonadotropin-releasing hormone (GnRH),
      luteinizing hormone (LH), and/or gonadal Te secretion. Available methods to test
      Leydig cell Te production include pharmacological stimulation with human
      chorionic gonadotropin (hCG). We reasoned that physiological lutropic signaling
      could be mimicked by pulsatile infusion of recombinant human (rh) LH during acute
      suppression of LH secretion. To this end, we studied eight young (ages 19-30 yr)
      and seven older (ages 61-73 yr) men in an experimental paradigm comprising 1)
      inhibition of overnight LH secretion with a potent selective GnRH-receptor
      antagonist (ganirelix, 2 mg sc), 2) intravenous infusion of consecutive pulses of
      rh LH (50 IU every 2 h), and 3) chemiluminometric assay of LH and Te
      concentrations sampled every 10 min for 26 h. Statistical analyses revealed that
      1) ganirelix suppressed LH and Te equally (> 75% median inhibition) in young and
      older men, 2) infused LH pulse profiles did not differ by age, and 3) successive
      intravenous pulses of rh LH increased concentrations of free Te (ng/dl) to 4.6 +/
      0.38 (young) and 2.1 +/- 0.14 (older; P < 0.001) and bioavailable Te (ng/dl) to
      337 +/- 20 (young) and 209 +/- 16 (older; P = 0.002). Thus controlled pulsatile
      rh LH drive that emulates physiological LH pulses unmasks significant impairment
      of short-term Leydig cell steroidogenesis in aging men. Whether more prolonged
      pulsatile LH stimulation would normalize this inferred defect is unknown.

PMID- 15572656
TI  - Myofibrillar and collagen protein synthesis in human skeletal muscle in young men
      after maximal shortening and lengthening contractions.
AB  - We aimed to determine whether there were differences in the extent and time
      course of skeletal muscle myofibrillar protein synthesis (MPS) and muscle
      collagen protein synthesis (CPS) in human skeletal muscle in an 8.5-h period
      after bouts of maximal muscle shortening (SC; average peak torque = 225 +/- 7
      N.m, means +/- SE) or lengthening contractions (LC; average peak torque = 299 +/-
      18 N.m) with equivalent work performed in each mode. Eight healthy young men
      (21.9 +/- 0.6 yr, body mass index 24.9 +/- 1.3 kg/m2) performed 6 sets of 10
      maximal unilateral LC of the knee extensors on an isokinetic dynamometer. With
      the contralateral leg, they then performed 6 sets of maximal unilateral SC with
      work matched to the total work performed during LC (10.9 +/- 0.7 vs. 10.9 +/- 0.8
      kJ, P = 0.83). After exercise, the participants consumed small intermittent meals
      to provide 0.1 g.kg(-1).h(-1) of protein and carbohydrate. Prior exercise
      elevated MPS above rest in both conditions, but there was a more rapid rise after
      LC (P < 0.01). The increases (P < 0.001) in CPS above rest were identical for
      both SC and LC and likely represent a remodeling of the myofibrillar basement
      membrane. Therefore, a more rapid rise in MPS after maximal LC could translate
      into greater protein accretion and muscle hypertrophy during chronic resistance
      training utilizing maximal LC.

PMID- 15572657
TI  - Exogenous amino acids stimulate human muscle anabolism without interfering with
      the response to mixed meal ingestion.
AB  - We sought to determine whether ingestion of a between-meal supplement containing
      30 g of carbohydrate and 15 g of essential amino acids (CAA) altered the
      metabolic response to a nutritionally mixed meal in healthy, recreationally
      active male volunteers. A control group (CON; n = 6, 38 +/- 8 yr, 86 +/- 10 kg,
      179 +/- 3 cm) received a liquid mixed meal [protein, 23.4 +/- 1.0 g (essential
      amino acids, 14.7 +/- 0.7 g); carbohydrate, 126.6 +/- 4.0 g; fat, 30.3 +/- 2.8 g]
      every 5 h (0830, 1330, 1830). The experimental group (SUP; n = 7, 36 +/- 10 yr,
      87 +/- 12 kg, 180 +/- 3 cm) consumed the same meals but, in addition, were given
      CAA supplements (1100, 1600, 2100). Net phenylalanine balance (NB) and fractional
      synthetic rate (FSR) were calculated during a 16-h primed constant infusion of L
      [ring-2H5]phenylalanine. Ingestion of a combination of CAA supplements and meals
      resulted in a greater mixed muscle FSR than ingestion of the meals alone (SUP,
      0.099 +/- 0.008; CON, 0.076 +/- 0.005%/h; P < 0.05). Both groups experienced an
      improvement in NB after the morning (SUP, -2.2 +/- 3.3; CON, -1.5 +/- 3.5 nmol x
      min(-1) x 100 ml leg volume(-1)) and evening meals (SUP, -9.7 +/- 4.3; CON, -6.7
      +/- 4.1 nmol x min(-1) x 100 ml leg volume(-1)). NB after CAA ingestion was
      significantly greater than after the meals, with values of 40.2 +/- 8.5 nmol x
      min(-1) x 100 ml leg volume(-1). These data indicate that CAA supplementation
      produces a greater anabolic effect than ingestion of intact protein but does not
      interfere with the normal metabolic response to a meal.

PMID- 15572658
TI  - 1,25(OH)2D3 acts as a bone-forming agent in the hormone-independent senescence
      accelerated mouse (SAM-P/6).
AB  - Recent studies suggest that vitamin D signaling regulates bone formation.
      However, the overall effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on bone
      turnover in vivo is still unclear. In this study, our aim was to examine the
      effect of 1,25(OH)2D3 on bone turnover in SAM-P/6, a hormone-independent mouse
      model of senile osteoporosis characterized by a decrease in bone formation. Male
      and female 4-mo-old SAM-P/6 mice were treated with 1,25(OH)2D3 (18 pmol/24 h) or
      vehicle for a period of 6 wk, and a group of age- and sex-matched nonosteoporotic
      animals was used as control. Bone mineral density (BMD) at the lumbar spine
      increased rapidly by >30 +/- 5% (P < 0.001) in 1,25(OH)2D3-treated SAM-P/6
      animals, whereas BMD decreased significantly by 18 +/- 2% (P < 0.01) in vehicle
      treated SAM-P/6 animals and remained stable in control animals during the same
      period. Static and dynamic bone histomorphometry indicated that 1,25(OH)2D3
      significantly increased bone volume and other parameters of bone quality as well
      as subperiosteal bone formation rate compared with vehicle-treated SAM-P/6 mice.
      However, no effect on trabecular bone formation was observed. This was
      accompanied by a marked decrease in the number of osteoclasts and eroded
      surfaces. A significant increase in circulating bone formation markers and a
      decrease in bone resorption markers was also observed. Finally, bone marrow
      cells, obtained from 1,25(OH)2D3-treated animals and cultured in the absence of
      1,25(OH)2D3, differentiated more intensely into osteoblasts compared with those
      derived from vehicle-treated mice cultured in the same conditions. Taken
      together, these findings demonstrate that 1,25(OH)2D3 acts simultaneously on bone
      formation and resorption to prevent the development of senile osteoporosis.

PMID- 15572659
TI  - Influence of RNA secondary structure on the pre-mRNA splicing process.

PMID- 15572660
TI  - A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene
      required for the endothelial response to phorbol esters.
AB  - We identified Ras guanine-releasing protein 3 (RasGRP3) as a guanine exchange
      factor expressed in blood vessels via an embryonic stem (ES) cell-based gene trap
      screen to identify novel vascular genes. RasGRP3 is expressed in embryonic blood
      vessels, down-regulated in mature adult vessels, and reexpressed in newly formed
      vessels during pregnancy and tumorigenesis. This expression pattern is consistent
      with an angiogenic function for RasGRP3. Although a loss-of-function mutation in
      RasGRP3 did not affect viability, RasGRP3 was up-regulated in response to
      vascular endothelial growth factor (VEGF) stimulation of human umbilical vein
      endothelial cells, placing RasGRP3 regulation downstream of VEGF signaling.
      Phorbol esters mimic the second messenger diacylglycerol (DAG) in activating both
      protein kinase C (PKC) and non-PKC phorbol ester receptors such as RasGRP3. ES
      cell-derived wild-type blood vessels exposed to phorbol myristate acetate (PMA)
      underwent extensive aberrant morphogenesis that resulted in the formation of
      large endothelial sheets rather than properly branched vessels. This response to
      PMA was completely dependent on the presence of RasGRP3, as mutant vessels were
      refractory to the treatment. Taken together, these findings show that endothelial
      RasGRP3 is up-regulated in response to VEGF stimulation and that RasGRP3
      functions as an endothelial cell phorbol ester receptor in a pathway whose
      stimulation perturbs normal angiogenesis. This suggests that RasGRP3 activity may
      exacerbate vascular complications in diseases characterized by excess DAG, such
      as diabetes.

PMID- 15572661
TI  - Negative modulation of androgen receptor transcriptional activity by Daxx.
AB  - The transcriptional activity of the androgen receptor (AR) modulated by positive
      or negative regulators plays a critical role in controlling the growth and
      survival of prostate cancer cells. Although numerous positive regulators have
      been identified, negative regulators of AR are less well understood. We report
      here that Daxx functions as a negative AR coregulator through direct protein
      protein interactions. Overexpression of Daxx suppressed AR-mediated promoter
      activity in COS-1 and LNCaP cells and AR-mediated prostate-specific antigen
      expression in LNCaP cells. Conversely, downregulation of endogenous Daxx
      expression by RNA interference enhances androgen-induced prostate-specific
      antigen expression in LNCaP cells. In vitro and in vivo interaction studies
      revealed that Daxx binds to both the amino-terminal and the DNA-binding domain of
      the AR. Daxx proteins interfere with the AR DNA-binding activity both in vitro
      and in vivo. Moreover, sumoylation of AR at its amino-terminal domain is involved
      in Daxx interaction and trans-repression. Together, these findings not only
      provide a novel role of Daxx in controlling AR transactivation activity but also
      uncover the mechanism underlying sumoylation-dependent transcriptional repression
      of the AR.

PMID- 15572662
TI  - Phosphorylation of progesterone receptor serine 400 mediates ligand-independent
      transcriptional activity in response to activation of cyclin-dependent protein
      kinase 2.
AB  - Human progesterone receptors (PR) are phosphorylated by cyclin-dependent protein
      kinase 2 (CDK2) at multiple sites, including Ser400. Herein, we have addressed
      the significance of phosphorylation of this residue. PR phospho-Ser400-specific
      antibodies revealed regulated phosphorylation of Ser400 in response to progestins
      and mitogens, and this correlated with increased CDK2 levels and activity.
      Expression of cyclin E elevated CDK2 activity and downregulated PR independently
      of ligand. Similarly, overexpression of activated mutant CDK2 increased PR
      transcriptional activity in the absence and presence of progestin. Mutation of PR
      Ser400 to alanine (S400A) blocked CDK2-induced PR activity in the absence, but
      not in the presence, of progestin. PR was unresponsive to activated CDK2 in
      breast cancer cells with elevated p27, and RNA interference knock-down of p27
      partially restored CDK2-induced ligand-independent PR activation. Similarly, in
      p27(-/-) mouse embryonic fibroblasts, elevated CDK2 activity increased wild-type
      (wt) but not S400A PR transcriptional activity in the absence of progestin. CDK2
      induced nuclear localization of unliganded wt but not S400A PR; liganded S400A PR
      exhibited delayed nuclear accumulation. These studies demonstrate that CDK2
      regulates PR in the absence of progestins via phosphorylation of Ser400, thus
      revealing a novel mechanism for upregulated PR transcriptional activity in human
      breast cancer cells expressing altered cell cycle regulatory molecules.

PMID- 15572663
TI  - Brk activates rac1 and promotes cell migration and invasion by phosphorylating
      paxillin.
AB  - Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3,
      SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a
      human metastatic breast tumor, and its overexpression is frequently observed in
      breast cancer and several other cancer types. However, the molecular mechanism by
      which this kinase participates in tumorigenesis remains poorly characterized. In
      the present study, we not only identified paxillin as the binding partner and
      substrate of Brk but also discovered a novel signaling pathway by which Brk
      mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show
      that EGF stimulation activates the catalytic activity of Brk, which in turn
      phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the
      activation of small GTPase Rac1 via the function of CrkII. Through this pathway,
      Brk is capable of promoting cell motility and invasion and functions as a
      mediator of EGF-induced migration and invasion. In accordance with these
      functional roles, Brk translocates to membrane ruffles, where it colocalizes with
      paxillin during cell migration. Together, our findings identify novel signaling
      and biological roles of Brk and indicate the first potential link between Brk and
      metastatic malignancy.

PMID- 15572664
TI  - Activation of p90 Rsk1 is sufficient for differentiation of PC12 cells.
AB  - We investigated the role of Rsk proteins in the nerve growth factor (NGF)
      signaling pathway in PC12 cells. When rat Rsk1 or murine Rsk2 proteins were
      transiently expressed, NGF treatment (100 ng/ml for 3 days) caused three- and
      fivefold increases in Rsk1 and Rsk2 activities, respectively. Increased
      activation of both wild-type Rsk proteins could be achieved by coexpression of a
      constitutively active (CA) mitogen-activated protein kinase (MAPK) kinase, MEK1
      DD, which is known to cause differentiation of PC12 cells even in the absence of
      NGF. Rsk1 and Rsk2 mutated in the PDK1-binding site were not activated by either
      NGF or MEK1-DD. Expression of constitutively active Rsk1 or Rsk2 in PC12 cells
      resulted in highly active proteins whose levels of activity did not change either
      with NGF treatment or after coexpression with MEK1-DD. Rsk2-CA expression had no
      detectable effect on the cells. However, expression of Rsk1-CA led to
      differentiation of PC12 cells even in the absence of NGF, as evidenced by neurite
      outgrowth. Differentiation was not observed with a nonactive Rsk1-CA that was
      mutated in the PDK1-binding site. Expression of Rsk1-CA did not lead to
      activation of the endogenous MAPK pathway, indicating that Rsk1 is sufficient to
      induce neurite outgrowth and is the only target of MAPK required for this effect.
      Collectively, our data demonstrate a key role for Rsk1 in the differentiation
      process of PC12 cells.

PMID- 15572665
TI  - Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes.
AB  - Microphthalmia transcription factor (MITF) and STAT3 are two transcription
      factors that play a major role in the regulation of growth and function in mast
      cells and melanocytes. In the present study, we explored the MITF-PIAS3-STAT3
      network of interactions, how these interactions regulate gene expression, and how
      cytokine-mediated phosphorylation of MITF and STAT3 is involved in the in vivo
      interplay between these three proteins. In NIH 3T3 cells stimulated via gp130
      receptor, transfected MITF was found to be phosphorylated at S409. Such
      phosphorylation of MITF leads to PIAS3 dissociation from MITF and its association
      with STAT3. Activation of mouse melanoma and mast cells through gp130 or c-Kit
      receptors induced the mobilization of PIAS3 from MITF to STAT3. In mast cells
      derived from MITF(di/di) mice, whose MITF lacks the Zip domain (PIAS3-binding
      domain), we found downregulation in mRNA levels of genes regulated by either MITF
      or STAT3. This regulatory mechanism is of considerable importance since it is
      likely to advance the deciphering of a role for MITF and STAT3 in mast cells and
      melanocytes.

PMID- 15572666
TI  - PIAS-1 is a checkpoint regulator which affects exit from G1 and G2 by sumoylation
      of p73.
AB  - p73 is a recently described member of the p53 family, and, like p53, it undergoes
      a number of posttranslational modifications. Here we show, by yeast two-hybrid
      screening, pull-down assays, and coimmunoprecipitation, that p73alpha, -beta, and
      -gamma bind to the protein inhibitor of activated STAT-1 (PIAS-1) and that this
      binding stabilizes p73. PIAS-1 also sumoylates p73alpha, although not the C
      terminally truncated isoforms p73beta and -gamma, and this requires the RING
      finger domain of PIAS-1. The DeltaNp73alpha isoform can also bind, and be
      sumoylated by, PIAS-1. PIAS-1-mediated sumoylation decreases p73 transcriptional
      activity on several target promoters, such as Bax. p73 is colocalized in the
      nucleus with PIAS-1, and sumoylated p73 is located exclusively in the nuclear
      matrix. PIAS-1 is expressed predominantly during S phase, and PIAS-1
      overexpression reduces p73-mediated transcription of p21, with a reduction of
      cells in G(1) and cell cycle reentry. Inhibition of endogenous PIAS-1 by RNA
      interference reduces the proportion of cells in S phase and induces G(2) arrest.
      These data suggest that PIAS-1, acting partly through binding and sumoylation of
      p73, is an important component of the cell cycle machinery.

PMID- 15572667
TI  - p38alpha mitogen-activated protein kinase plays a critical role in cardiomyocyte
      survival but not in cardiac hypertrophic growth in response to pressure overload.
AB  - The molecular mechanism for the transition from cardiac hypertrophy, an adaptive
      response to biomechanical stress, to heart failure is poorly understood. The
      mitogen-activated protein kinase p38alpha is a key component of stress response
      pathways in various types of cells. In this study, we attempted to explore the in
      vivo physiological functions of p38alpha in hearts. First, we generated mice with
      floxed p38alpha alleles and crossbred them with mice expressing the Cre
      recombinase under the control of the alpha-myosin heavy-chain promoter to obtain
      cardiac-specific p38alpha knockout mice. These cardiac-specific p38alpha knockout
      mice were born normally, developed to adulthood, were fertile, exhibited a normal
      life span, and displayed normal global cardiac structure and function. In
      response to pressure overload to the left ventricle, they developed significant
      levels of cardiac hypertrophy, as seen in controls, but also developed cardiac
      dysfunction and heart dilatation. This abnormal response to pressure overload was
      accompanied by massive cardiac fibrosis and the appearance of apoptotic
      cardiomyocytes. These results demonstrate that p38alpha plays a critical role in
      the cardiomyocyte survival pathway in response to pressure overload, while
      cardiac hypertrophic growth is unaffected despite its dramatic down-regulation.

PMID- 15572668
TI  - C-terminal anchoring of mid1p to membranes stabilizes cytokinetic ring position
      in early mitosis in fission yeast.
AB  - mid1p is a key factor for the central positioning of the cytokinetic ring in
      Schizosaccharomyces pombe. In interphase and early mitosis, mid1p forms a medial
      cortical band overlying the nucleus, which may represent a landmark for
      cytokinetic ring assembly. It compacts before anaphase into a tight ring with
      other cytokinetic ring components. We show here that mid1p binds to the medial
      cortex by at least two independent means. First, mid1p C-terminus association
      with the cortex requires a putative amphipathic helix adjacent to mid1p nuclear
      localization sequence (NLS), which is predicted to insert directly into the lipid
      bilayer. This association is stabilized by the polybasic NLS. mid1p mutated
      within the helix and the NLS forms abnormal filaments in early mitosis that are
      not properly anchored to the medial cortex. Misplaced rings assemble in late
      mitosis, indicating that mid1p C-terminus binding to membranes stabilizes
      cytokinetic ring position. Second, the N terminus of mid1p has the ability to
      associate faintly with the medial cortex and is sufficient to form tight rings.
      In addition, we show that mid1p oligomerizes. We propose that membrane-bound
      oligomers of mid1p assemble recruitment "platforms" for cytokinetic ring
      components at the medial cortex and stabilize the ring position during its
      compaction.

PMID- 15572669
TI  - The CRM1 nuclear export receptor controls pathological cardiac gene expression.
AB  - Diverse pathological insults trigger a cardiac remodeling process during which
      myocytes undergo hypertrophy, with consequent decline in cardiac function and
      eventual heart failure. Multiple transcriptional regulators of pathological
      cardiac hypertrophy are controlled at the level of subcellular distribution. For
      example, prohypertrophic transcription factors belonging to the nuclear factor of
      activated T cells (NFAT) and GATA families are subject to CRM1-dependent nuclear
      export but are rapidly relocalized to the nucleus in response to cues for
      hypertrophic growth. Here, we demonstrate that the antihypertrophic chromatin
      modifying enzyme histone deacetylase 5 (HDAC5) is shuttled out of the
      cardiomyocyte nucleus via a CRM1-mediated pathway in response to diverse signals
      for hypertrophy. CRM1 antagonists block the agonist-mediated nuclear export of
      HDAC 5 and repress pathological gene expression and associated hypertrophy of
      cultured cardiomyocytes. Conversely, CRM1 activity is dispensable for
      nonpathological cardiac gene activation mediated by thyroid hormone and insulin
      like growth factor 1, agonists that fail to trigger the nuclear export of HDAC5.
      These results suggest a selective role for CRM1 in derepression of pathological
      cardiac genes via its neutralizing effects on antihypertrophic factors such as
      HDAC5. Pharmacological approaches targeting CRM1-dependent nuclear export in
      heart muscle may have salutary effects on cardiac function by suppressing
      maladaptive changes in gene expression evoked by stress signals.

PMID- 15572670
TI  - C/EBPalpha is a DNA damage-inducible p53-regulated mediator of the G1 checkpoint
      in keratinocytes.
AB  - The basic leucine zipper transcription factor, CCAAT/enhancer binding protein
      alpha (C/EBPalpha), is abundantly expressed in keratinocytes of the skin;
      however, its function in skin is poorly characterized. UVB radiation is
      responsible for the majority of human skin cancers. In response to UVB-induced
      DNA damage, keratinocytes activate cell cycle checkpoints that arrest cell cycle
      progression and prevent replication of damaged DNA, allowing time for DNA repair.
      We report here that UVB radiation is a potent inducer of C/EBPalpha in human and
      mouse keratinocytes, as well as in mouse skin in vivo. UVB irradiation of
      keratinocytes resulted in the transcriptional up-regulation of C/EBPalpha mRNA,
      producing a >70-fold increase in C/EBPalpha protein levels. N-Methyl-N'-nitro-N
      nitrosoguanidine, etoposide, and bleomycin also induced C/EBPalpha. UVB-induced
      C/EBPalpha was accompanied by an increase in p53 protein and caffeine, an
      inhibitor of ataxia-telangiectasia-mutated kinase, and ataxia-telangiectasia
      mutated and Rad3-related kinase inhibited UVB-induced increases in both
      C/EBPalpha and p53. UVB irradiation of p53-null or mutant p53-containing
      keratinocytes failed to induce C/EBPalpha. UVB irradiation of C/EBPalpha
      knockdown keratinocytes displayed a greatly diminished DNA damage G(1)
      checkpoint, and this was associated with increased sensitivity to UVB-induced
      apoptosis. Our results uncover a novel role for C/EBPalpha as a p53-regulated DNA
      damage-inducible gene that has a critical function in the DNA damage G(1)
      checkpoint response in keratinocytes.

PMID- 15572671
TI  - Peroxisome proliferator-activated receptor gamma controls Muc1 transcription in
      trophoblasts.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is essential for placental development. Here, we show that the mucin gene Muc1 is
      a PPARgamma target, whose expression is lost in PPARgamma null placentas. During
      differentiation of trophoblast stem cells, PPARgamma is strongly induced, and
      Muc1 expression is upregulated by the PPARgamma agonist rosiglitazone. Muc1
      promoter is activated strongly and specifically by liganded PPARgamma but not
      PPARalpha or PPARdelta. A PPAR binding site (DR1) in the proximal Muc1 promoter
      acts as a basal silencer in the absence of PPARgamma, and its cooperation with a
      composite upstream enhancer element is both necessary and sufficient for
      PPARgamma-dependent induction of Muc1. In the placenta, MUC1 protein is localized
      exclusively to the apical surface of the labyrinthine trophoblast around maternal
      blood sinuses, resembling its luminal localization on secretory epithelia. Last,
      variably penetrant maternal blood sinus dilation in Muc1-deficient placentas
      suggests that Muc1 regulation by PPARgamma contributes to normal placental
      development but also that the essential functions of PPARgamma in the organ are
      mediated by other targets.

PMID- 15572672
TI  - Definition of a short region of XPG necessary for TFIIH interaction and stable
      recruitment to sites of UV damage.
AB  - XPG is the human endonuclease that cuts 3' to DNA lesions during nucleotide
      excision repair. Missense mutations in XPG can lead to xeroderma pigmentosum
      (XP), whereas truncated or unstable XPG proteins cause Cockayne syndrome (CS),
      normally yielding life spans of <7 years. One XP-G individual who had advanced
      XP/CS symptoms at 28 years has been identified. The genetic, biochemical, and
      cellular defects in this remarkable case provide insight into the onset of XP and
      CS, and they reveal a previously unrecognized property of XPG. Both of this
      individual's XPG alleles produce a severely truncated protein, but an infrequent
      alternative splice generates an XPG protein lacking seven internal amino acids,
      which can account for his very slight cellular UV resistance. Deletion of XPG
      amino acids 225 to 231 does not abolish structure-specific endonuclease activity.
      Instead, this region is essential for interaction with TFIIH and for the stable
      recruitment of XPG to sites of local UV damage after the prior recruitment of
      TFIIH. These results define a new functional domain of XPG, and they demonstrate
      that recruitment of DNA repair proteins to sites of damage does not necessarily
      lead to productive repair reactions. This observation has potential implications
      that extend beyond nucleotide excision repair.

PMID- 15572673
TI  - Novel role for a sterol response element binding protein in directing
      spermatogenic cell-specific gene expression.
AB  - Sperm are highly specialized cells, and their formation requires the synthesis of
      a large number of unique mRNAs. However, little is known about the
      transcriptional mechanisms that direct male germ cell differentiation. Sterol
      response element binding protein 2gc (SREBP2gc) is a spermatogenic cell-enriched
      isoform of the ubiquitous transcription factor SREBP2, which in somatic cells is
      required for homeostatic regulation of cholesterol. SREBP2gc is selectively
      enriched in spermatocytes and spermatids, and, due to its novel structure, its
      synthesis is not subject to cholesterol feedback control. This suggested that
      SREBP2gc has unique cell- and stage-specific functions during spermatogenesis.
      Here, we demonstrate that this factor activates the promoter for the
      spermatogenesis-related gene proacrosin in a cell-specific manner. Multiple
      SREBP2gc response elements were identified within the 5'-flanking and proximal
      promoter regions of the proacrosin promoter. Mutating these elements greatly
      diminished in vivo expression of this promoter in spermatogenic cells of
      transgenic mice. These studies define a totally new function for an SREBP as a
      transactivator of male germ cell-specific gene expression. We propose that
      SREBP2gc is part of a cadre of spermatogenic cell-enriched isoforms of
      ubiquitously expressed transcriptional coregulators that were specifically
      adapted in concert to direct differentiation of the male germ cell lineage.

PMID- 15572674
TI  - Interaction and functional cooperation between the LIM protein FHL2, CBP/p300,
      and beta-catenin.
AB  - Transcriptional activation of gene expression by Wnt signaling is driven by the
      association of beta-catenin with TCF/LEF factors and the recruitment of
      transcriptional coactivators. It has been shown that the LIM protein FHL2 and the
      acetyltransferase CBP/p300 individually stimulate beta-catenin transactivating
      activity and that beta-catenin is acetylated by p300. Here, we report that FHL2
      and CBP/p300 synergistically enhanced beta-catenin/TCF-mediated transcription
      from Wnt-responsive promoters and that the acetyltransferase activity of CBP/p300
      was involved in the cooperation. CBP/p300 interacted directly with FHL2,
      predominantly through the CH3 domain but not the histone acetyltransferase
      domain, and different regions of CBP/p300 were involved in FHL2 and beta-catenin
      binding. We provided evidence for the formation of a ternary complex by FHL2,
      CBP/p300, and beta-catenin and for colocalization of the three proteins in the
      nucleus. In murine FHL2(-/-) embryo fibroblasts, the transactivation activity of
      beta-catenin/TCF was markedly reduced, and this defect could be restored by
      exogenous expression of FHL2. However, CBP/p300 were still able to coactivate the
      beta-catenin/TCF complex in FHL2(-/-) cells, suggesting that FHL2 is dispensable
      for the coactivator function of CBP/p300 on beta-catenin. Furthermore, we found
      that FHL2 significantly increased acetylation of beta-catenin by p300 in vivo.
      Finally, we showed that FHL2, CBP/p300, and beta-catenin could synergistically
      activate androgen receptor-mediated transcription, indicating that the
      synergistic coactivator function is not restricted to TCF/LEF.

PMID- 15572675
TI  - NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum
      stress and apoptosis in human aortic smooth muscle cells.
AB  - The mechanisms involved in the cytotoxic action of oxysterols in the pathogenesis
      of atherosclerosis still remain poorly understood. Among the major oxysterols
      present in oxidized low-density lipoprotein, we show here that 7-ketocholesterol
      (7-Kchol) induces oxidative stress and/or apoptotic events in human aortic smooth
      muscle cells (SMCs). This specific effect of 7-Kchol is mediated by a robust
      upregulation (threefold from the basal level) of Nox-4, a reactive oxygen species
      (ROS)-generating NAD(P)H oxidase homologue. This effect was highlighted by
      silencing Nox-4 expression with a specific small interfering RNA, which
      significantly reduced the 7-Kchol-induced production of ROS and abolished
      apoptotic events. Furthermore, the 7-Kchol activating pathway included an early
      triggering of endoplasmic reticulum stress, as assessed by transient
      intracellular Ca(2+) oscillations, and the induction of the expression of the
      cell death effector CHOP and of GRP78/Bip chaperone via the activation of IRE-1,
      all hallmarks of the unfolded protein response (UPR). We also showed that 7-Kchol
      activated the IRE-1/Jun-NH(2)-terminal kinase (JNK)/AP-1 signaling pathway to
      promote Nox-4 expression. Silencing of IRE-1 and JNK inhibition downregulated Nox
      4 expression and subsequently prevented the UPR-dependent cell death induced by 7
      Kchol. These findings demonstrate that Nox-4 plays a key role in 7-Kchol-induced
      SMC death, which is consistent with the hypothesis that Nox-4/oxysterols are
      involved in the pathogenesis of atherosclerosis.

PMID- 15572676
TI  - FAST is a survival protein that senses mitochondrial stress and modulates TIA-1
      regulated changes in protein expression.
AB  - The Fas-activated serine/threonine phosphoprotein (FAST) is tethered to the outer
      mitochondrial membrane, where it interacts with BCL-X(L) (17). Here we show that
      RNA interference-mediated knockdown of endogenous FAST results in apoptosis,
      whereas overexpressed recombinant FAST inhibits Fas- and UV-induced apoptosis,
      indicating that FAST is a survival protein. The antiapoptotic effects of FAST are
      regulated by interactions with the translational silencer TIA-1: a FAST mutant
      lacking its TIA-1-binding domain does not inhibit apoptosis, and overexpressed
      recombinant TIA-1 inhibits the antiapoptotic effects of FAST. Because the
      antiapoptotic effects of FAST require ongoing protein synthesis, we hypothesized
      that FAST might function by preventing TIA-1-mediated silencing of mRNAs encoding
      inhibitors of apoptosis. Consistent with this hypothesis, FAST promotes the
      expression of cotransfected reporter proteins, a process that requires its TIA-1
      binding domain and is inhibited by overexpressed recombinant TIA-1. More
      compellingly, recombinant FAST increases the expression of endogenous cIAP-1 and
      XIAP, but not GAPDH, in transfected HeLa cells. Because FAST is released from
      mitochondria in cells undergoing Fas- or UV-induced apoptosis, we propose that
      FAST serves as a sensor of mitochondrial stress that modulates a TIA-1-regulated
      posttranscriptional stress response program.

PMID- 15572677
TI  - DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus
      formation.
AB  - The yeast SNM1/PSO2 gene specifically functions in DNA interstrand cross-link
      (ICL) repair, and its role has been suggested to be separate from other DNA
      repair pathways. In vertebrates, there are three homologs of SNM1 (SNM1A, SNM1B,
      and SNM1C/Artemis; SNM1 family proteins) whose functions are largely unknown. We
      disrupted each of the SNM1 family genes in the chicken B-cell line DT40. Both
      SNM1A- and SNM1B-deficient cells were sensitive to cisplatin but not to X-rays,
      whereas SNM1C/Artemis-deficient cells exhibited sensitivity to X-rays but not to
      cisplatin. SNM1A was nonepistatic with XRCC3 (homologous recombination), RAD18
      (translesion synthesis), FANCC (Fanconi anemia), and SNM1B in ICL repair. SNM1A
      protein formed punctate nuclear foci depending on the conserved SNM1 (metallo
      beta-lactamase) domain. PIAS1 was found to physically interact with SNM1A, and
      they colocalized at nuclear foci. Point mutations in the SNM1 domain, which
      disrupted the interaction with PIAS1, led to mislocalization of SNM1A in the
      nucleus and loss of complementation of snm1a cells. These results suggest that
      interaction between SNM1A and PIAS1 is required for ICL repair.

PMID- 15572678
TI  - Nuclear export of hnRNP Hrp1p and nuclear export of hnRNP Npl3p are linked and
      influenced by the methylation state of Npl3p.
AB  - Eukaryotic mRNA processing and export are mediated by a series of complexes
      composed of heterogeneous nuclear ribonucleoproteins (hnRNPs). Many of these
      hnRNPs are methylated at arginine residues within their RGG domains. Although
      cellular arginine methylation is required for the efficient nuclear export of
      several hnRNPs, its role in this process is unknown. To address this question, we
      replaced the methylated RGG tripeptides of two hnRNPs, Npl3p and Hrp1p, with KGG.
      We found that these substitutions specifically abolish their methylation but have
      different effects on their nuclear export activity. Although the efficient export
      of Hrp1p requires cellular methyltransferase activity, the modification of Hrp1p
      itself is dispensable. In contrast, we found that Npl3 arginine methylation not
      only facilitates its own export but also is required for Hrp1p to efficiently
      exit the nucleus. Consistent with this observation, we found that Npl3p and Hrp1p
      exist in a ribonucleoprotein complex. We provide the first evidence that the
      arginine methylation of a particular protein directly affects its activity.
      Efficient export does not require methylation per se, but unmethylated arginine
      residues lead to retention of hnRNPs. Thus, arginine methylation serves to mask
      the Npl3p RGG domain for efficient ribonucleoprotein export.

PMID- 15572679
TI  - Restoration of NF-kappaB activation by tumor necrosis factor alpha receptor
      complex-targeted MEKK3 in receptor-interacting protein-deficient cells.
AB  - Receptor-interacting protein (RIP) plays a critical role in tumor necrosis factor
      alpha (TNF-alpha)-induced NF-kappaB activation. However, the mechanism by which
      RIP mediates TNF-alpha-induced signal transduction is not fully understood. In
      this study, we reconstituted RIP-deficient Jurkat T cells with a fusion protein
      composed of full-length MEKK3 and the death domain of RIP (MEKK3-DD). In these
      cells, MEKK3-DD substitutes for RIP and directly associates with TRADD in TNF
      receptor complexes following TNF-alpha stimulation. We found that TNF-alpha
      induced NF-kappaB activation was fully restored by MEKK3-DD in these cells. In
      contrast, expression of a fusion protein composed of NEMO, a component of the
      IkappaB kinase complex, and the death domain of RIP (NEMO-DD) cannot restore TNF
      alpha-induced NF-kappaB activation in RIP-deficient cells. These results indicate
      that the role of RIP is to specifically recruit MEKK3 to the TNF-alpha receptor
      complex, whereas the forced recruitment of NEMO to the TNF-alpha receptor complex
      is insufficient for TNF-alpha-induced NF-kappaB activation. Although MEKK2 has a
      high degree of homology with MEKK3, MEKK2-DD, unlike MEKK3-DD, also fails to
      restore TNF-alpha-induced NF-kappaB activation in RIP-deficient cells, indicating
      that RIP-dependent recruitment of MEKK3 plays a specific role in TNF-alpha
      signaling.

PMID- 15572680
TI  - 5-fluorouracil enhances exosome-dependent accumulation of polyadenylated rRNAs.
AB  - The antimetabolite 5-fluorouracil (5FU) is a widely used chemotherapeutic for the
      treatment of solid tumors. Although 5FU slows DNA synthesis by inhibiting the
      ability of thymidylate synthetase to produce dTMP, the drug also has significant
      effects on RNA metabolism. Recent genome-wide assays for 5FU-induced
      haploinsufficiency in Saccharomyces cerevisiae identified genes encoding
      components of the RNA processing exosome as potential targets of the drug. In
      this report, we used DNA microarrays to analyze the effect of 5FU on the yeast
      transcriptome and found that the drug causes the accumulation of polyadenylated
      fragments of the 27S rRNA precursor and that defects in the nuclear
      exoribonuclease Rrp6p enhance this effect. The size distribution of these RNAs
      and their sensitivity to Rrp6p suggest that they are normally degraded by the
      nuclear exosome and a 5'-3' exoribonuclease. Consistent with this hypothesis, 5FU
      inhibits the growth of RRP6 mutants with defects in the degradation function of
      the enzyme and it interferes with the degradation of an rRNA precursor. The
      detection of poly(A)(+) pre-RNAs in strains defective in various steps in
      ribosome biogenesis suggests that the production of poly(A)(+) pre-rRNAs may be a
      general result of defects in rRNA processing. These findings suggest that 5FU
      inhibits an exosome-dependent surveillance pathway that degrades polyadenylated
      precursor rRNAs.

PMID- 15572681
TI  - Sp3 proteins negatively regulate beta myosin heavy chain gene expression during
      skeletal muscle inactivity.
AB  - In adult skeletal muscle, beta myosin heavy chain (betaMyHC) gene expression is
      primarily restricted to slow type I fibers; however, its expression is down
      regulated in response to muscle inactivity. Little is known about the signaling
      pathways and transcription factors that mediate this important functional
      response. This study demonstrates that increased binding of Sp3 to GC-rich
      elements in the betaMyHC promoter is a critical event in down-regulation of
      betaMyHC gene expression under non-weight-bearing conditions. Conversely, binding
      of Sp3 to these elements decreased while Sp1 binding increased with nuclear
      extracts from plantaris muscle exposed to mechanical overload, a stimulus that
      increases betaMyHC gene expression. In addition, these experiments revealed the
      existence of an Sp4-DNA binding complex when using adult skeletal muscle nuclear
      extract was used but not when nuclear extracts from cultured myotubes were used.
      Sp3 proteins are competitive inhibitors of Sp1-mediated betaMyHC reporter gene
      transactivation in both Drosophila SL-2 and mouse C2C12 myotubes. Sp4 is a weak
      activator of betaMyHC gene expression in SL-2 cells, which lack endogenous Sp1
      activity, but does not activate betaMyHC gene expression in C2C12 myotubes, which
      have high levels of Sp1. These results suggest that competitive binding of Sp
      family proteins regulate betaMyHC gene transcription in response to altered
      neuromuscular activity.

PMID- 15572682
TI  - Functional genetic screen for genes involved in senescence: role of Tid1, a
      homologue of the Drosophila tumor suppressor l(2)tid, in senescence and cell
      survival.
AB  - We performed a genetic suppressor element screen to identify genes whose
      inhibition bypasses cellular senescence. A normalized library of fragmented cDNAs
      was used to select for elements that promote immortalization of rat embryo
      fibroblasts. Fragments isolated by the screen include those with homology to
      genes that function in intracellular signaling, cellular adhesion and contact,
      protein degradation, and apoptosis. They include mouse Tid1, a homologue of the
      Drosophila tumor suppressor gene l(2)tid, recently implicated in modulation of
      apoptosis as well as gamma interferon and NF-kappaB signaling. We show that GSE
      Tid1 enhances immortalization by human papillomavirus E7 and simian virus 40 T
      antigen and cooperates with activated ras for transformation. Expression of Tid1
      is upregulated upon cellular senescence in rat and mouse embryo fibroblasts and
      premature senescence of REF52 cells triggered by activated ras. In accordance
      with this, spontaneous immortalization of rat embryo fibroblasts is suppressed
      upon ectopic expression of Tid1. Modulation of endogenous Tid1 activity by GSE
      Tid1 or Tid1-specific RNA interference alleviates the suppression of tumor
      necrosis factor alpha-induced NF-kappaB activity by Tid1. We also show that NF
      kappaB sequence-specific binding is strongly downregulated upon senescence in rat
      embryo fibroblasts. We therefore propose that Tid1 contributes to senescence by
      acting as a repressor of NF-kappaB signaling.

PMID- 15572683
TI  - Growth rate and cell size modulate the synthesis of, and requirement for, G1
      phase cyclins at start.
AB  - In Saccharomyces cerevisiae, commitment to cell cycle progression occurs at
      Start. Progression past Start requires cell growth and protein synthesis, a
      minimum cell size, and G(1)-phase cyclins. We examined the relationships among
      these factors. Rapidly growing cells expressed, and required, dramatically more
      Cln protein than did slowly growing cells. To clarify the role of cell size, we
      expressed defined amounts of CLN mRNA in cells of different sizes. When Cln was
      expressed at nearly physiological levels, a critical threshold of Cln expression
      was required for cell cycle progression, and this critical threshold varied with
      both cell size and growth rate: as cells grew larger, they needed less CLN mRNA,
      but as cells grew faster, they needed more Cln protein. At least in part, large
      cells had a reduced requirement for CLN mRNA because large cells generated more
      Cln protein per unit of mRNA than did small cells. When Cln was overexpressed, it
      was capable of promoting Start rapidly, regardless of cell size or growth rate.
      In summary, the amount of Cln required for Start depends dramatically on both
      cell size and growth rate. Large cells generate more Cln1 or Cln2 protein for a
      given amount of CLN mRNA, suggesting the existence of a novel posttranscriptional
      size control mechanism.

PMID- 15572684
TI  - Leukemogenesis caused by incapacitated GATA-1 function.
AB  - GATA-1 is essential for the development of erythroid and megakaryocytic lineages.
      We found that GATA-1 gene knockdown female (GATA-1.05/X) mice frequently develop
      a hematopoietic disorder resembling myelodysplastic syndrome that is
      characterized by the accumulation of progenitors expressing low levels of GATA-1.
      In this study, we demonstrate that GATA-1.05/X mice suffer from two distinct
      types of acute leukemia, an early-onset c-Kit-positive nonlymphoid leukemia and a
      late-onset B-lymphocytic leukemia. Since GATA-1 is an X chromosome gene, two
      types of hematopoietic cells reside within heterozygous GATA-1 knockdown mice,
      bearing either an active wild-type GATA-1 allele or an active mutant GATA-1.05
      allele. In the hematopoietic progenitors with the latter allele, low-level GATA-1
      expression is sufficient to support survival and proliferation but not
      differentiation, leading to the accumulation of progenitors that are easily
      targeted by oncogenic stimuli. Since such leukemia has not been observed in GATA
      1-null/X mutant mice, we conclude that the residual GATA-1 activity in the
      knockdown mice contributes to the development of the malignancy. This de novo
      model recapitulates the acute crisis found in preleukemic conditions in humans.

PMID- 15572685
TI  - The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and
      TIP60.
AB  - The c-MYC oncoprotein functions as a sequence-specific transcription factor. The
      ability of c-MYC to activate transcription relies in part on the recruitment of
      cofactor complexes containing the histone acetyltransferases mammalian GCN5
      (mGCN5)/PCAF and TIP60. In addition to acetylating histones, these enzymes have
      been shown to acetylate other proteins involved in transcription, including
      sequence-specific transcription factors. This study was initiated in order to
      determine whether c-MYC is a direct substrate of mGCN5 and TIP60. We report here
      that mGCN5/PCAF and TIP60 acetylate c-MYC in vivo. By using nanoelectrospray
      tandem mass spectrometry to examine c-MYC purified from human cells, the major
      mGCN5-induced acetylation sites have been mapped. Acetylation of c-MYC by either
      mGCN5/PCAF or TIP60 results in a dramatic increase in protein stability. The data
      reported here suggest a conserved mechanism by which acetyltransferases regulate
      c-MYC function by altering its rate of degradation.

PMID- 15572686
TI  - The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle
      development.
AB  - The nuclear orphan receptor COUP-TFII is widely expressed in multiple tissues and
      organs throughout embryonic development, suggesting that COUP-TFII is involved in
      multiple aspects of embryogenesis. Because of the early embryonic lethality of
      COUP-TFII knockout mice, the role of COUP-TFII during limb development has not
      been determined. COUP-TFII is expressed in lateral plate mesoderm of the early
      embryo prior to limb bud formation. In addition, COUP-TFII is also expressed in
      the somites and skeletal muscle precursors of the limbs. Therefore, in order to
      study the potential role of COUP-TFII in limb and skeletal muscle development, we
      bypassed the early embryonic lethality of the COUP-TFII mutant by using two
      methods. First, embryonic chimera analysis has revealed an obligatory role for
      COUP-TFII in limb bud outgrowth since mutant cells are unable to contribute to
      the distally growing limb mesenchyme. Second, we used a conditional-knockout
      approach to ablate COUP-TFII specifically in the limbs. Loss of COUP-TFII in the
      limbs leads to hypoplastic skeletal muscle development, as well as shorter limbs.
      Taken together, our results demonstrate that COUP-TFII plays an early role in
      limb bud outgrowth but not limb bud initiation. Also, COUP-TFII is required for
      appropriate development of the skeletal musculature of developing limbs.

PMID- 15572687
TI  - c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, is essential for tumor
      necrosis factor alpha-induced c-Jun kinase activation and apoptosis.
AB  - Two ubiquitously expressed isoforms of c-Jun N-terminal protein kinase (JNK),
      JNK1 and JNK2, have shared functions and different functions. However, the
      molecular mechanism is unknown. Here we report that JNK1, but not JNK2, is
      essential for tumor necrosis factor alpha (TNF-alpha)-induced c-Jun kinase
      activation, c-Jun expression, and apoptosis. Using mouse fibroblasts deficient in
      either Jnk1 or Jnk2, we found that JNK1 was activated by TNF-alpha, whereas JNK2
      activation was negligible. In addition, JNK2 interfered with JNK1 activation via
      its "futile" phosphorylation by upstream kinases. Consequently, expression and
      activation of c-Jun, which depends on JNK activity, were impaired in Jnk1 null
      cells but enhanced in Jnk2 null cells. TNF-alpha-induced apoptosis was also
      suppressed in Jnk1 null fibroblasts but increased in Jnk2 null cells. Thus, our
      results provide a molecular mechanism underlying the different biological
      functions of JNK isoforms.

PMID- 15572688
TI  - Counting of Rif1p and Rif2p on Saccharomyces cerevisiae telomeres regulates
      telomere length.
AB  - Telomere length is negatively regulated by proteins of the telomeric DNA-protein
      complex. Rap1p in Saccharomyces cerevisiae binds the telomeric TG(1-3) repeat
      DNA, and the Rap1p C terminus interacts with Rif1p and Rif2p. We investigated how
      these three proteins negatively regulate telomere length. We show that direct
      tethering of each Rif protein to a telomere shortens that telomere proportionally
      to the number of tethered molecules, similar to previously reported counting of
      Rap1p. Surprisingly, Rif proteins could also regulate telomere length even when
      the Rap1p C terminus was absent, and tethered Rap1p counting was completely
      dependent on the Rif proteins. Thus, Rap1p counting is in fact Rif protein
      counting. In genetic settings that cause telomeres to be abnormally long,
      tethering even a single Rif2p molecule was sufficient for maximal effectiveness
      in preventing the telomere overelongation. We show that a heterologous protein
      oligomerization domain, the mammalian PDZ domain, when fused to Rap1p can confer
      telomere length control. We propose that a nucleation and spreading mechanism is
      involved in forming the higher-order telomere structure that regulates telomere
      length.

PMID- 15572689
TI  - Cooperative regulation of the cell division cycle by the protein kinases RAF and
      AKT.
AB  - The RAS-activated RAF-->MEK-->extracellular signal-regulated kinase (ERK) and
      phosphatidylinositol 3'-kinase (PI3'-kinase)-->PDK1-->AKT signaling pathways are
      believed to cooperate to promote the proliferation of normal cells and the
      aberrant proliferation of cancer cells. To explore the mechanisms that underlie
      such cooperation, we have derived cells harboring conditionally active, steroid
      hormone-regulated forms of RAF and AKT. These cells permit the assessment of the
      biological and biochemical effects of activation of these protein kinases either
      alone or in combination with one another. Under conditions where activation of
      neither RAF nor AKT alone promoted S-phase progression, coactivation of both
      kinases elicited a robust proliferative response. Moreover, under conditions
      where high-level activation of RAF induced G(1) cell cycle arrest, activation of
      AKT bypassed the arrest and promoted S-phase progression. At the level of the
      cell cycle machinery, RAF and AKT cooperated to induce cyclin D1 and repress
      p27(Kip1) expression. Repression of p27(Kip1) was accompanied by a dramatic
      reduction in KIP1 mRNA and was observed in primary mouse embryo fibroblasts
      derived from mice either lacking SKP2 or expressing a T187A mutated form of
      p27(Kip1). Consistent with these observations, pharmacological inhibition of MEK
      or PI3'-kinase inhibited the effects of activated RAS on the expression of
      p27(Kip1) in NIH 3T3 fibroblasts and in a panel of bona fide human pancreatic
      cancer cell lines. Furthermore, we demonstrated that AKT activation led to
      sustained activation of cyclin/cdk2 complexes that occurred concomitantly with
      the removal of RAF-induced p21(Cip1) from cyclin E/cdk2 complexes. Cumulatively,
      these data strongly suggest that the RAF-->MEK-->ERK and PI3'K-->PDK-->AKT
      signaling pathways can cooperate to promote G(0)-->G(1)-->S-phase cell cycle
      progression in both normal and cancer cells.

PMID- 15572690
TI  - Expression profiling of murine acute promyelocytic leukemia cells reveals
      multiple model-dependent progression signatures.
AB  - Leukemia results from the expansion of self-renewing hematopoietic cells that are
      thought to contain mutations that contribute to disease initiation and
      progression. Studies of the gene expression profiles of human acute myeloid
      leukemia samples has allowed their classification based on the presence of
      translocations and French-American-British subtypes, but it is not yet clear
      whether their molecular signatures reflect the initiating mutations or mutations
      acquired during progression. To begin to address this question, we examined the
      expression profiles of normal murine promyelocyte-enriched samples,
      nontransformed murine promyelocytes expressing human promyelocytic leukemia
      retinoic acid receptor alpha (PML-RARalpha) fusion gene, and primary acute
      promyelocytic leukemia cells. The expression profile of nontransformed cells
      expressing PML-RARalpha was remarkably similar to that of wild-type
      promyelocytes. In contrast, the expression profiles of fully transformed cells
      from three acute promyelocytic leukemia model systems were all different,
      suggesting that the expression signature of acute promyelocytic leukemia cells
      reflects the genetic changes that contributed to progression. To further evaluate
      these progression events, we compared two high-penetrance acute promyelocytic
      leukemia models that both commonly acquire an interstitial deletion of chromosome
      2 during progression. The two models exhibited distinct gene expression profiles,
      suggesting that the dominant molecular signatures of murine acute promyelocytic
      leukemia can be influenced by several independent progression events.

PMID- 15572691
TI  - Nonphosphorylated human La antigen interacts with nucleolin at nucleolar sites
      involved in rRNA biogenesis.
AB  - La is a RNA-binding protein implicated in multiple pathways related to the
      production of tRNAs, ribosomal proteins, and other components of the
      translational machinery (D. J. Kenan and J. D. Keene, Nat. Struct. Mol. Biol.
      11:303-305, 2004). While most La is phosphorylated and resides in the
      nucleoplasm, a fraction is in the nucleolus, the site of ribosome production,
      although the determinants of this localization are incompletely known. In
      addition to its conserved N-terminal domain, human La harbors a C-terminal domain
      that contains an atypical RNA recognition motif and a short basic motif (SBM)
      adjacent to phosphoserine-366. We report that nonphosphorylated La (npLa) is
      concentrated in nucleolar sites that correspond to the dense fibrillar component
      that harbors nascent pol I transcripts as well as fibrillarin and nucleolin,
      which function in early phases of rRNA maturation. Affinity purification and
      native immunoprecipitation of La and fluorescence resonance energy transfer in
      the nucleolus reveal close association with nucleolin. Moreover, La lacking the
      SBM does not localize to nucleoli. Lastly, La exhibits SBM-dependent,
      phosphorylation-sensitive interaction with nucleolin in a yeast two-hybrid assay.
      The data suggest that interaction with nucleolin is, at least in part,
      responsible for nucleolar accumulation of La and that npLa may be involved in
      ribosome biogenesis.

PMID- 15572692
TI  - ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine
      morphogenesis, and deficits in learning and memory.
AB  - The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling
      pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins
      localize to sites of actin polymerization in protrusive membrane structures and
      regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell
      morphogenesis and migration in vivo. Homozygous deletion of murine abi2 produced
      abnormal phenotypes in the eye and brain, the tissues with the highest Abi2
      expression. In the absence of Abi2, secondary lens fiber orientation and
      migration were defective in the eye, without detectable defects in proliferation,
      differentiation, or apoptosis. These phenotypes were consistent with the
      localization of Abi2 at adherens junctions in the developing lens and at nascent
      epithelial cell adherens junctions in vitro. Downregulation of Abi expression by
      RNA interference impaired adherens junction formation and correlated with
      downregulation of the Wave actin-nucleation promoting factor. Loss of Abi2 also
      resulted in cell migration defects in the neocortex and hippocampus, abnormal
      dendritic spine morphology and density, and severe deficits in short- and long
      term memory. These findings support a role for Abi2 in the regulation of
      cytoskeletal dynamics at adherens junctions and dendritic spines, which is
      critical for intercellular connectivity, cell morphogenesis, and cognitive
      functions.

PMID- 15572693
TI  - PRAM-1 is required for optimal integrin-dependent neutrophil function.
AB  - PML-retinoic acid receptor alpha (RARalpha) regulated adaptor molecule 1 (PRAM-1)
      is an intracellular adaptor molecule that is upregulated during the induced
      granulocytic differentiation of promyelocytic leukemic cells and during normal
      human myelopoiesis. This report describes the generation of PRAM-1-deficient mice
      and an analysis of the function of this adaptor in neutrophil differentiation and
      mature neutrophil function. We demonstrate here that neutrophil differentiation
      is not impaired in PRAM-1-deficient mice and that PRAM-1-deficient neutrophils
      function normally following engagement of Fcgamma receptors. In contrast, mature
      PRAM-1-null neutrophils exhibit significant defects in adhesion-dependent
      reactive oxygen intermediate production and degranulation. Surprisingly, other
      integrin-dependent responses, such as cell spreading and activation of several
      signaling pathways, are normal. Together, these findings demonstrate the
      uncoupling of key integrin-dependent responses in the absence of PRAM-1 and show
      this adaptor to be critical for select integrin functions in neutrophils.

PMID- 15572694
TI  - The mitochondrial SDHD gene is required for early embryogenesis, and its partial
      deficiency results in persistent carotid body glomus cell activation with full
      responsiveness to hypoxia.
AB  - The SDHD gene encodes one of the two membrane-anchoring proteins of the succinate
      dehydrogenase (complex II) of the mitochondrial electron transport chain. This
      gene has recently been proposed to be involved in oxygen sensing because
      mutations that cause loss of its function produce hereditary familiar
      paraganglioma, a tumor of the carotid body (CB), the main arterial chemoreceptor
      that senses oxygen levels in the blood. Here, we report the generation of a SDHD
      knockout mouse, which to our knowledge is the first mammalian model lacking a
      protein of the electron transport chain. Homozygous SDHD(-/-) animals die at
      early embryonic stages. Heterozygous SDHD(+/-) mice show a general,
      noncompensated deficiency of succinate dehydrogenase activity without alterations
      in body weight or major physiological dysfunction. The responsiveness to hypoxia
      of CBs from SDHD(+/-) mice remains intact, although the loss of an SDHD allele
      results in abnormal enhancement of resting CB activity due to a decrease of K(+)
      conductance and persistent Ca(2+) influx into glomus cells. This CB overactivity
      is linked to a subtle glomus cell hypertrophy and hyperplasia. These observations
      indicate that constitutive activation of SDHD(+/-) glomus cells precedes CB tumor
      transformation. They also suggest that, contrary to previous beliefs,
      mitochondrial complex II is not directly involved in CB oxygen sensing.

PMID- 15572695
TI  - Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent
      ubiquitin ligase complex.
AB  - The bZIP transcription factor Nrf2 controls a genetic program that protects cells
      from oxidative damage and maintains cellular redox homeostasis. Keap1, a BTB
      Kelch protein, is the major upstream regulator of Nrf2 and controls both the
      subcellular localization and steady-state levels of Nrf2. In this report, we
      demonstrate that Keap1 functions as a substrate adaptor protein for a Cul3
      dependent E3 ubiquitin ligase complex. Keap1 assembles into a functional E3
      ubiquitin ligase complex with Cul3 and Rbx1 that targets multiple lysine residues
      located in the N-terminal Neh2 domain of Nrf2 for ubiquitin conjugation both in
      vivo and in vitro. Keap1-dependent ubiquitination of Nrf2 is inhibited following
      exposure of cells to quinone-induced oxidative stress and sulforaphane, a cancer
      preventive isothiocyanate. A mutant Keap1 protein containing a single cysteine-to
      serine substitution at residue 151 within the BTB domain of Keap1 is markedly
      resistant to inhibition by either quinone-induced oxidative stress or
      sulforaphane. Inhibition of Keap1-dependent ubiquitination of Nrf2 correlates
      with decreased association of Keap1 with Cul3. Neither quinone-induced oxidative
      stress nor sulforaphane disrupts association between Keap1 and Nrf2. Our results
      suggest that the ability of Keap1 to assemble into a functional E3 ubiquitin
      ligase complex is the critical determinant that controls steady-state levels of
      Nrf2 in response to cancer-preventive compounds and oxidative stress.

PMID- 15572696
TI  - Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by
      CBP/p300 recruitment.
AB  - Cell signaling affects gene expression by regulating the activity of
      transcription factors. Here, we report that mitogen-activated protein kinase
      (MAPK) phosphorylation of Ets-1 and Ets-2, at a conserved site N terminal to
      their Pointed (PNT) domains, resulted in enhanced transactivation by preferential
      recruitment of the coactivators CREB binding protein (CBP) and p300. We
      discovered this phosphorylation-augmented interaction in an unbiased affinity
      chromatography screen of HeLa nuclear extracts by using either mock-treated or
      ERK2-phosphorylated ETS proteins as ligands. Binding between purified proteins
      demonstrated a direct interaction. Both the phosphoacceptor site, which lies in
      an unstructured region, and the PNT domain were required for the interaction.
      Minimal regions that were competent for induced CBP/p300 binding in vitro also
      supported MAPK-enhanced transcription in vivo. CBP coexpression potentiated MEK1
      stimulated Ets-2 transactivation of promoters with Ras-responsive elements.
      Furthermore, CBP and Ets-2 interacted in a phosphorylation-enhanced manner in
      vivo. This study describes a distinctive interface for a transcription factor
      coactivator complex and demonstrates a functional role for inducible CBP/p300
      binding. In addition, our findings decipher the mechanistic link between Ras/MAPK
      signaling and two specific transcription factors that are relevant to both normal
      development and tumorigenesis.

PMID- 15572697
TI  - Evidence for histone eviction in trans upon induction of the yeast PHO5 promoter.
AB  - The yeast PHO5 promoter is a model system for the role of chromatin in eukaryotic
      gene regulation. Four positioned nucleosomes in the repressed state give way to
      an extended DNase I hypersensitive site upon induction. Recently this
      hypersensitive site was shown to be devoid of histone DNA contacts. This raises
      the mechanistic question of how histones are removed from the promoter. A
      displacement in trans or movement in cis, the latter according to the well
      established nucleosome sliding mechanism, are the major alternatives. In this
      study, we embedded the PHO5 promoter into the context of a small plasmid which
      severely restricts the space for nucleosome sliding along the DNA in cis. Such a
      construct would either preclude the chromatin transition upon induction
      altogether, were it to occur in cis, or gross changes in chromatin around the
      plasmid would be the consequence. We observed neither. Instead, promoter opening
      on the plasmid was indistinguishable from opening at the native chromosomal
      locus. This makes a sliding mechanism for the chromatin transition at the PHO5
      promoter highly unlikely and points to histone eviction in trans.

PMID- 15572698
TI  - Amino acid substitutions in yeast TFIIF confer upstream shifts in transcription
      initiation and altered interaction with RNA polymerase II.
AB  - Transcription factor IIF (TFIIF) is required for transcription of protein
      encoding genes by eukaryotic RNA polymerase II. In contrast to numerous studies
      establishing a role for higher eukaryotic TFIIF in multiple steps of the
      transcription cycle, relatively little has been reported regarding the functions
      of TFIIF in the yeast Saccharomyces cerevisiae. In this study, site-directed
      mutagenesis, plasmid shuffle complementation assays, and primer extension
      analyses were employed to probe the functional domains of the S. cerevisiae TFIIF
      subunits Tfg1 and Tfg2. Analyses of 35 Tfg1 alanine substitution mutants and 19
      Tfg2 substitution mutants identified 5 mutants exhibiting altered properties in
      vivo. Primer extension analyses revealed that the conditional growth properties
      exhibited by the tfg1-E346A, tfg1-W350A, and tfg2-L59K mutants were associated
      with pronounced upstream shifts in transcription initiation in vivo. Analyses of
      double mutant strains demonstrated functional interactions between the Tfg1
      mutations and mutations in Tfg2, TFIIB, and RNA polymerase II. Importantly,
      biochemical results demonstrated an altered interaction between mutant TFIIF
      protein and RNA polymerase II. These results provide direct evidence for the
      involvement of S. cerevisiae TFIIF in the mechanism of transcription start site
      utilization and support the view that a TFIIF-RNA polymerase II interaction is a
      determinant in this process.

PMID- 15572700
TI  - CDC initiative targets HIV research gaps in black and Hispanic communities.

PMID- 15572699
TI  - Transactivation of E2F-regulated genes by polyomavirus large T antigen: evidence
      for a two-step mechanism.
AB  - Polyomavirus large T antigen transactivates a variety of genes whose products are
      involved in S phase induction. These genes are regulated by the E2F family of
      transcription factors, which are under the control of the pocket protein
      retinoblastoma protein and its relatives p130 and p107. The viral protein causes
      a dissociation of E2F-pocket protein complexes that results in transactivation of
      the genes. This reaction requires the N-terminal binding site for pocket proteins
      and the J domain that binds chaperones. We found earlier that a mutation of the
      zinc finger located within the C-terminal domain, a region assumed to function
      mainly in the replication of viral DNA, also interferes with transactivation.
      Here we show that binding of the histone acetyltransferase coactivator complex
      CBP/p300-PCAF to the C terminus correlates with the ability of large T antigen to
      transactivate genes. This interaction results in promoter-specific acetylation of
      histones. Inactive mutant proteins with changes within the C-terminal domain were
      nevertheless able to dissociate the E2F pocket protein complexes, indicating that
      this dissociation is a necessary but insufficient step in the T antigen-induced
      transactivation of genes. It has to be accompanied by a second step involving the
      T antigen-mediated recruitment of a histone acetyltransferase complex.

PMID- 15572701
TI  - "New dawn" for Botswana: offering free HIV treatment--and hope. Interview with
      Ernest Darkoh, MD, MPH.

PMID- 15572702
TI  - Noninvasive heart valve procedures seen as potential alternative to surgery.

PMID- 15572703
TI  - "European CDC" moves forward: effort expected to help Europe fight epidemics.

PMID- 15572704
TI  - Shuffling mouse's genetic deck may illuminate causes of complex diseases.

PMID- 15572708
TI  - Adolescents with depression.

PMID- 15572709
TI  - Adolescents with depression.

PMID- 15572710
TI  - Adolescents with depression.

PMID- 15572711
TI  - Adolescents with depression.

PMID- 15572712
TI  - Spontaneous regression of cancerous tumors detected by mammography screening.

PMID- 15572713
TI  - Vitamin K deficiency and hepatocellular carcinoma.

PMID- 15572714
TI  - Androgen suppression plus radiation for prostate cancer.

PMID- 15572715
TI  - Prioritizing influenza vaccination.

PMID- 15572716
TI  - Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering
      drugs.
AB  - CONTEXT: Lipid-lowering agents are widely prescribed in the United States.
      Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are
      not available. OBJECTIVE: To estimate the incidence of rhabdomyolysis in patients
      treated with different statins and fibrates, alone and in combination, in the
      ambulatory setting. DESIGN, SETTING, AND PATIENTS: Drug-specific inception
      cohorts of statin and fibrate users were established using claims data from 11
      managed care health plans across the United States. Patients with at least 180
      days of prior health plan enrollment were entered into the cohorts between
      January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or
      combined statin-fibrate therapy. MAIN OUTCOME MEASURE: Incidence rates of
      rhabdomyolysis per 10,000 person-years of treatment, number needed to treat, and
      relative risk of rhabdomyolysis. RESULTS: In 252,460 patients treated with lipid
      lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during
      treatment. Average incidence per 10,000 person-years for monotherapy with
      atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI],
      0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82
      (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time
      was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72
      216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a
      fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use.
      Per year of therapy, the number needed to treat to observe 1 case of
      rhabdomyolysis was 22,727 for statin monotherapy, 484 for older patients with
      diabetes mellitus who were treated with both a statin and fibrate, and ranged
      from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate.
      CONCLUSIONS: Rhabdomyolysis risk was similar and low for monotherapy with
      atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased
      risk, especially in older patients with diabetes mellitus. Cerivastatin combined
      with fibrate conferred a risk of approximately 1 in 10 treated patients per year.

PMID- 15572717
TI  - Thyroid status, disability and cognitive function, and survival in old age.
AB  - CONTEXT: Despite the equivocal outcomes of randomized controlled trials, general
      clinical opinion favors screening and treatment of elderly individuals with
      subclinical thyroid disorders. OBJECTIVES: To determine whether subclinical
      thyroid dysfunction should be treated in old age and the long-term impact of
      thyroid dysfunction on performance and survival in old age. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective, observational, population-based follow-up study
      within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in
      the municipality of Leiden, the Netherlands. A total of 599 participants were
      followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7
      [1.4] years). MAIN OUTCOME MEASURES: Complete thyroid status at baseline;
      disability in daily life, depressive symptoms, cognitive function, and mortality
      from age 85 years through 89 years. RESULTS: Plasma levels of thyrotropin and
      free thyroxine were not associated with disability in daily life, depressive
      symptoms, and cognitive impairment at baseline or during follow-up. Increasing
      levels of thyrotropin were associated with a lower mortality rate that remained
      after adjustments were made for baseline disability and health status. The hazard
      ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77
      (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD
      increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95%
      CI, 1.04-1.30; P = .009). CONCLUSIONS: In the general population of the oldest
      old, elderly individuals with abnormally high levels of thyrotropin do not
      experience adverse effects and may have a prolonged life span. However, evidence
      for not treating elderly individuals can only come from a well-designed,
      randomized placebo-controlled clinical trial.

PMID- 15572718
TI  - Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed
      to iodine 131 from the hanford nuclear site.
AB  - CONTEXT: Approximately 740,000 Ci (2.73 x 10(16) Bq) of iodine 131 (131I) were
      released to the atmosphere from the Hanford Nuclear Site in Washington State from
      1944 through 1957. The risk of thyroid disease resulting from prolonged
      environmental 131I exposure is poorly understood. OBJECTIVE: The Hanford Thyroid
      Disease Study (HTDS) was conducted to determine if thyroid disease is increased
      among persons exposed as children to atmospheric releases of 131I from Hanford.
      DESIGN: Retrospective cohort study. Exposure could have occurred from December
      1944 through 1957. Follow-up occurred until the time of the HTDS examination
      (December 1992-September 1997). Participants' thyroid radiation doses from
      Hanford's 131I releases were estimated from interview data regarding residence
      and dietary histories. SETTING: The cohort included a sample of all births from
      1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern
      Washington State. PARTICIPANTS: Of 5199 individuals identified, 4350 were located
      alive and 3440 were evaluable; ie, had sufficient data for dose estimation and
      received an HTDS evaluation for thyroid disease, including a thyroid ultrasound,
      physical examination, and fine needle biopsy if required to evaluate thyroid
      nodularity. MAIN OUTCOME MEASURES: Thyroid cancer, benign thyroid nodules, total
      neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism.
      RESULTS: There was no evidence of a relationship between Hanford radiation dose
      and the cumulative incidence of any of the outcomes. These results remained
      unchanged after taking into account several factors that might confound the
      relationship between radiation dose and the outcomes of interest. CONCLUSION:
      These results do not support the hypothesis that exposure during infancy and
      childhood to 131I at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure
      circumstances experienced by our study participants increases the risk of the
      forms of thyroid disease evaluated in this study.

PMID- 15572719
TI  - Etiology of pruritic papular eruption with HIV infection in Uganda.
AB  - CONTEXT: A frequent cause of human immunodeficiency virus (HIV)-related morbidity
      in sub-Saharan Africa is a commonly occurring, intensely pruritic skin rash. The
      resulting scars are disfiguring and stigmatizing. Despite the substantial
      prevalence of pruritic papular eruption (PPE) among HIV-infected Africans, the
      cause has been elusive. OBJECTIVE: To determine the etiology of PPE occurring in
      HIV-infected individuals. DESIGN, SETTING, AND PATIENTS: Cross-sectional study of
      HIV-infected patients with active PPE from clinics in Uganda conducted from May
      19 through June 6, 2003. Enrollment occurred in the month preceding May 19. Each
      participant was clinically examined by 2 dermatologists, had laboratory studies
      performed, was administered an epidemiologic questionnaire, and had a skin biopsy
      of a new lesion evaluated by a dermatopathologist. MAIN OUTCOME MEASURES:
      Histological characteristics of new pruritic lesions. Other assessments included
      CD4 cell count, eosinophil count, and physician-assessed rash severity. RESULTS:
      Of 109 patients meeting inclusion criteria, 102 (93.6%) completed the study. The
      CD4 cell counts in this study population were generally low (median, 46/microL)
      and inversely related to increasing rash severity (median CD4 cell counts: 122
      for mild, 41 for moderate, and 9 for severe; P<.001 for trend). Eighty-six
      patients (84%; 95% confidence interval, 77%-91%) had biopsy findings
      characteristic of arthropod bites. Patients with arthropod bites on biopsy had
      significantly higher peripheral eosinophil counts (median, 330 vs 180/microL; P =
      .02) and had a trend toward lower CD4 cell counts (median, 40 vs 99/microL; P =
      .07) than those without histological evidence of arthropod bites. CONCLUSIONS:
      Pruritic papular eruption occurring in HIV-infected individuals may be a reaction
      to arthropod bites. We hypothesize that this condition reflects an altered and
      exaggerated immune response to arthropod antigens in a subset of susceptible HIV
      infected patients.

PMID- 15572720
TI  - Potential for conflict of interest in the evaluation of suspected adverse drug
      reactions: use of cerivastatin and risk of rhabdomyolysis.
AB  - CONTEXT: In recent years, US patients have increasingly been the first to receive
      new medications, some of which are subsequently discovered to have suspected
      adverse drug reactions (SADRs). As a result, the challenge of early detection has
      largely shifted to the US postmarketing systems. OBJECTIVE: To review the
      association between the use of cerivastatin sodium and the risk of rhabdomyolysis
      in an effort to illustrate the operation and limitations of the current US
      postmarketing safety-surveillance system. DATA SOURCES AND SELECTION: For the
      published literature, we used previous reviews and MEDLINE searches from all
      years through 2003. For the unpublished literature, we used internal company
      documents that have become part of the public record during a trial in Nueces
      County, Texas. DATA SYNTHESIS: In the published literature, cerivastatin was
      associated with much larger risks of rhabdomyolysis than other statins. Although
      only a small percentage of cerivastatin users also took gemfibrozil,
      approximately half of the case reports of rhabdomyolysis occurred in users of
      this combination therapy, and a cerivastatin-gemfibrozil interaction was
      supported by the results of a 3-day pharmacokinetic study. In internal company
      documents, multiple case reports suggested a drug-drug interaction within
      approximately 100 days of the launch in 1998; however, the company did not add a
      contraindication about the concomitant use of cerivastatin and gemfibrozil to the
      package insert for more than 18 months. Unpublished data available in July 1999
      also suggested an increased risk of rhabdomyolysis associated with high doses of
      cerivastatin monotherapy. In late 1999 and early 2000, company scientists
      conducted high-quality analyses of the US Food and Drug Administration adverse
      event reporting system data. These analyses suggested that compared with
      atorvastatin calcium, cerivastatin monotherapy substantially increased the risk
      of rhabdomyolysis. To our knowledge, these findings were not disseminated or
      published. The company continued to conduct safety studies, some of them
      inadequately designed to assess the risk of rhabdomyolysis, until cerivastatin
      was removed from the market in August 2001. CONCLUSIONS: Despite limitations of
      the available data, the asymmetry between the information available to the
      company and the information available to patients and physicians seems striking.
      A subjective element is present in the effort to infer whether or not the
      occurrence of untoward outcomes in users of a particular drug was actually the
      consequence of the use of that drug, and, under the current system, a
      pharmaceutical company's appraisal of SADRs may be influenced by economic
      considerations. Such an appraisal would best be made by an independent group. The
      US Congress should mandate and provide adequate support for independent reviews
      and analysis of postmarketing data.

PMID- 15572721
TI  - A 64-year-old woman with a thyroid nodule.

PMID- 15572722
TI  - Potential for conflict of interest in the evaluation of suspected adverse drug
      reactions: a counterpoint.

PMID- 15572723
TI  - Postmarketing surveillance--lack of vigilance, lack of trust.

PMID- 15572724
TI  - Thyroid disease in the oldest old: the exception to the rule.

PMID- 15572725
TI  - Bayer's response to "potential for conflict of interest in the evaluation of
      suspected adverse drug reactions: use of cerivastatin and risk of
      rhabdomyolysis".

PMID- 15572726
TI  - JAMA patient page. Thyroid nodules.

PMID- 15572727
TI  - Long-term survival rates of patients with prostate cancer in the prostate
      specific antigen screening era: population-based estimates for the year 2000 by
      period analysis.
AB  - PURPOSE: In the era of widespread prostate specific antigen (PSA) screening, a
      large proportion of older men have to live with a diagnosis of prostate cancer.
      In this study, we applied a new method for up-to-date analysis of long-term
      survival to evaluate if and to what extent these patients still have any excess
      mortality compared to the general population. METHODS: Five- and 10-year absolute
      and relative survival rates for the year 2000 were derived from the 1973 to 2000
      database of the Surveillance, Epidemiology and End Results Program using the
      recently introduced period analysis methodology. RESULTS: Overall, 5- and 10-year
      relative survival rates were approximately 99% and 95%; that is, excess mortality
      compared with the general population was as low as 1% and 5% within 5 and 10
      years following diagnosis, respectively. Two-thirds of patients were diagnosed
      with well or moderately differentiated localized/regional prostate cancer, and
      among these patients, 5- and 10-year relative survival rates were above 100%
      (indicating the lack of any excess mortality) at all ages. CONCLUSION: While the
      value of PSA screening for lowering mortality due to prostate cancer remains to
      be shown by randomized clinical trials, the majority of patients diagnosed with
      prostate cancer in the PSA screening era do not have excess mortality compared to
      the general population under current patterns of medical care. This information
      may be important for both clinical management of, and for patients' coping with,
      the disease.

PMID- 15572728
TI  - Targeted for destruction: the molecular basis for development of novel
      therapeutic strategies in renal cell cancer.

PMID- 15572729
TI  - Period analysis of prostate cancer survival.

PMID- 15572730
TI  - Imatinib-induced regression of AIDS-related Kaposi's sarcoma.
AB  - PURPOSE: Activation of the platelet-derived growth factor (PDGF) and c-kit
      receptors has been proposed as important in mediating the growth of AIDS-related
      Kaposi's sarcoma (KS). We investigated the response of KS to the PDGF receptor
      (PDGFR)/c-kit inhibitor, imatinib mesylate, and investigated the effect of this
      therapy on critical signal transduction intermediates. PATIENTS AND METHODS: Ten
      male patients with AIDS-related cutaneous KS, which progressed despite
      chemotherapy and/or highly active antiretroviral therapy, received imatinib
      mesylate administered orally, 300 mg twice daily. Clinical response was
      determined by serial tumor measurements. To determine biologic and histologic
      response, skin lesion biopsies were obtained at baseline and following 4 weeks of
      therapy. RESULTS: Five of 10 participants had a partial response by tumor
      measurements. Biopsies after 4 weeks of therapy demonstrated histologic
      regression in four of six patients. Four patients' tumor biopsies were assessable
      for immunohistochemistry end points pre- and post-therapy. These demonstrated
      inhibition of PDGFR and its downstream effector, extracellular receptor kinase,
      which is a member of the mitogen-activated protein kinase family. The most common
      adverse event was diarrhea, which led to dose reduction in six patients.
      CONCLUSION: Imatinib mesylate administered orally twice daily for AIDS-related KS
      results in clinical and histologic regression of cutaneous KS lesions within 4
      weeks. These promising results demonstrate that inhibition of the c-kit and/or
      PDGF receptors may represent an effective strategy for treating KS.

PMID- 15572731
TI  - Downregulation of Smac/DIABLO expression in renal cell carcinoma and its
      prognostic significance.
AB  - PURPOSE: Second mitochondria-derived activator of caspase/direct inhibitor of
      apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a
      protein that is released from mitochondria in response to apoptotic stimuli and
      promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore,
      Smac/DIABLO plays an important regulatory role in the sensitization of cancer
      cells to both immune- and drug-induced apoptosis. However, little is known about
      the clinical significance of Smac/DIABLO in various cancers, including renal cell
      carcinoma (RCC). This study examined Smac/DIABLO expression in 78 healthy kidneys
      and 78 RCCs. MATERIALS AND METHODS: The level of Smac/DIABLO expression was
      quantified by Western blot analysis using nonfixed fresh frozen tissues. RESULTS:
      The expression of Smac/DIABLO was lower in RCC compared with the autologous
      normal kidney. Sixty-four (82%) of 78 of RCC expressed Smac/DIABLO, and 18% were
      negative, whereas 100% of normal kidney tissues were positive. In stage I/II RCC,
      96% expressed Smac/DIABLO, whereas only 50% expressed Smac/DIABLO in stage
      III/IV. Smac/DIABLO expression inversely correlated with the grade of RCC.
      Patients with RCC expressing Smac/DIABLO had a longer postoperative disease
      specific survival than those without Smac/DIABLO expression in the 5-year follow
      up. Transfection with Smac/DIABLO cDNA enhanced tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) -mediated and cisplatin-mediated cytotoxicity
      in RCC. CONCLUSION: The present study demonstrates for the first time that
      Smac/DIABLO expression was downregulated in RCC and that no Smac/DIABLO
      expression in RCC predicted a worse prognosis. In addition, transfection with
      Smac/DIABLO sensitized RCC to TRAIL/cisplatin-induced apoptosis. These results
      suggest that Smac/DIABLO expression in RCC may be used as a prognostic parameter,
      and that enhancement of Smac/DIABLO expression in RCC may potentiate
      immunotherapy and chemotherapy.

PMID- 15572732
TI  - Bulimia nervosa: 25 years on.

PMID- 15572733
TI  - Genetic approaches to alcohol dependence.

PMID- 15572734
TI  - Acute and transient psychotic disorders: precursors, epidemiology, course and
      outcome.
AB  - BACKGROUND: ICD-10 has introduced the diagnostic group acute and transient
      psychotic disorders (ATPDs; F23). AIMS: To validate the nosological
      distinctiveness of ICD-10 ATPDs by following up an inception cohort with first
      episode psychosis. METHOD: All patients with first-episode psychosis identified
      in Nottingham between 1992 and 1994 and diagnosed using ICD-10 criteria were
      reassessed 3 years later. ATPD outcomes were compared with schizophrenia and
      affective psychosis. Multivariate analyses were conducted to determine whether
      acute onset and early remission predicted favourable 3-year outcome in first
      episode psychosis. RESULTS: Of 168 cases of first-episode psychosis, 32 (19%)
      received an intake diagnosis of ATPD. The diagnosis of ATPD was stable in women
      over 3 years, but not in men. Outcomes in ATPD were better than in schizophrenia
      and similar to affective psychosis. In non-affective psychoses, favourable
      outcomes were a function of gender and premorbid functioning rather than acute
      onset and early remission. CONCLUSIONS: The ICD-10 criteria for ATPDs identify a
      diagnostically unstable group of disorders. Acute onset and early remission do
      not independently predict favourable outcome over 3 years in first-episode
      psychosis.

PMID- 15572735
TI  - Diagnostic stability in a Dutch psychosis incidence cohort.
AB  - BACKGROUND: No study outside the UK has examined the diagnostic stability of
      psychotic disorders in a population-based sample. AIMS: To determine diagnostic
      stability in a Dutch population-based psychosis incidence cohort, to examine the
      frequencies of diagnostic shifts to and from schizophrenic disorders and to
      report the revised relative risks of schizophrenic disorders for immigrants.
      METHOD: A 30-month follow-up study assessed the cohort (n=181) by means of face
      to-face diagnostic interviews. RESULTS: Diagnostic stability of schizophrenic
      disorders was high (91%), but lower for other psychotic disorders. At follow-up,
      the initial diagnosis was adjusted to schizophrenic disorder more often than that
      the reverse occurred. Almost half (49%) of the patients who were not initially
      diagnosed as having a schizophrenic disorder received this diagnosis at follow
      up. The relative risks for most immigrant groups were stable. CONCLUSIONS:
      Schizophrenic disorders are underdiagnosed, rather than overdiagnosed, at first
      presentation.

PMID- 15572736
TI  - Family history of primary movement disorders as a predictor for neuroleptic
      induced extrapyramidal symptoms.
AB  - BACKGROUND: A genetic susceptibility to extrapyramidal symptoms caused by
      treatment with neuroleptic medication has been suggested. AIMS: To identify
      predictor variables for neuroleptic-induced extrapyramidal symptoms, particularly
      considering family history of primary movement disorders. METHOD: We investigated
      100 in-patients receiving a stable neuroleptic medication with regard to
      occurrence of extrapyramidal symptoms, drug history and detailed family history
      of primary movement disorders. RESULTS: Step-wise logistic regression analysis
      revealed that a positive family history was a significant predictor for lifetime
      prevalence of extrapyramidal symptoms, including reported and currently observed
      symptoms. The duration of exposure to neuroleptic medication and age were further
      predictors. CONCLUSIONS: Our findings underline the notion of genetic
      susceptibility for secondary extrapyramidal symptoms and suggest possible shared
      genetic factors in primary and secondary movement disorders as well as psychotic
      disorders.

PMID- 15572737
TI  - Efficacy of olanzapine combined with valproate or lithium in the treatment of
      dysphoric mania.
AB  - BACKGROUND: Few controlled studies examine the treatment of depressive features
      in mania. AIMS: To evaluate the efficacy of olanzapine, in combination with
      lithium or valproate, for treating depressive symptoms associated with mania.
      METHOD: Secondary analysis of a 6-week, double-blind, randomised study of
      olanzapine (5-20 mg/day) or placebo combined with ongoing valproate or lithium
      open treatment for 344 patients in mixed or manic episodes. This analysis focused
      on a dysphoric subgroup with baseline Hamilton Rating Scale for Depression (HRSD)
      total scores of 20 or over contrasted with non-dysphoric patients. RESULTS: In
      the dysphoric subgroup (n=85) mean HRSD total score improvement was significantly
      greater in olanzapine co-therapy patients than in those receiving placebo plus
      lithium or valproate (P<0.001). Substantial contributors to this superiority
      included the HRSD Maier sub-scale (P=0.013) and the suicide item (P=0.001). Total
      Young Mania Rating Scale improvement was also superior with olanzapine co
      therapy. CONCLUSIONS: In patients with acute dysphoric mania, addition of
      olanzapine to ongoing lithium or valproate monotherapy significantly improved
      depressive symptom, mania and suicidality ratings.

PMID- 15572738
TI  - Rates and predictors of mental illness in gay men, lesbians and bisexual men and
      women: Results from a survey based in England and Wales.
AB  - BACKGROUND: There is a dearth of research into the mental health of gay men,
      lesbians and bisexual men and women in the UK. AIMS: To assess rates and possible
      predictors of mental illness in these groups. METHOD: A comprehensive assessment
      was made of the psychological and social well-being of a sample of gay men,
      lesbians and bisexual men and women, identified using 'snowball' sampling.
      RESULTS: Of the 1285 gay, lesbian and bisexual respondents who took part, 556
      (43%) had mental disorder as defined by the revised Clinical Interview Schedule
      (CIS - R). Out of the whole sample, 361 (31%) had attempted suicide. This was
      associated with markers of discrimination such as recent physical attack (OR=1.7,
      95% CI 1.3-2.3) and school bullying (OR=1.4, 95% CI 1.1-2.0), but not with higher
      scores on the CIS-R. CONCLUSIONS: Gay, lesbian and bisexual men and women have
      high levels of mental disorder, possibly linked with discrimination.

PMID- 15572739
TI  - Socio-economic differentials in mental disorders and suicide attempts in
      Australia.
AB  - BACKGROUND: Responses to mental disorders usually focus on treatment; socio
      economic conditions are less likely to be considered. AIMS: To examine social
      determinants of mental disorders and attempted suicide in Australia. METHOD: Data
      from the 1997 Australian National Survey of Mental Health and Wellbeing (n=10
      641) were used to estimate associations between socio-economic status, mental
      disorders and attempted suicide. Logistic regression was used to adjust for age,
      urban/rural residence and country of birth. Socio-economic status differentials
      in suicide attempts were also adjusted for mental disorders. RESULTS: Significant
      increasing gradients from high to low levels of education and occupational status
      (employed) were evident for affective disorders and anxiety disorders in both men
      and women and for substance use disorders in men. Similar gradients were found
      for suicide attempts, which decreased after adjusting for mental disorders, but
      remained significant in the working-age employed. CONCLUSIONS: These findings
      suggest social causation of mental disorders and suicide attempts, and the need
      for social and economic responses beyond provision of mental health services.

PMID- 15572740
TI  - Suicide in custody: case-control study.
AB  - BACKGROUND: Few risk factors and indicators of vulnerability for suicide in
      custody are known so far. AIMS: A case-control study was conducted to investigate
      the relevance of criminal history, psychiatric morbidity and social integration
      to suicide in prison. METHOD: For every suicide that occurred in an Austrian
      correctional institution between 1975 and 1999, two controls matched for
      correctional institution, gender, nationality, age, custodial status and time of
      admission were selected. Psychiatric characteristics, previous suicidal
      behaviour, criminal history and indicators of social integration were compared.
      RESULTS: Of 250 recorded suicides, 220 personal files were available and matched
      to 440 controls. The most important predictors for suicide in custody were a
      history of suicidality (status following attempted suicide and suicide threat),
      psychiatric diagnosis, psychotropic medication, a highly violent index offence
      and single- cell accommodation. CONCLUSIONS: A significant finding is the
      importance of suicidal behaviour as an indicator of risk of suicide in
      correctional institutions, which until now has been a matter of debate. This
      study demonstrates the need for staff to take suicidal behaviour as seriously in
      custodial settings as in any other circumstances.

PMID- 15572741
TI  - People with learning disabilities in a low secure in-patient unit: comparison of
      offenders and non-offenders.
AB  - BACKGROUND: People with learning disability who exhibit challenging behaviour are
      frequently segregated from services and local teams are often reluctant to
      receive them back into their care. This situation is worse in those whose
      challenging behaviour includes a forensic history, but the difference between
      those labelled as challenging and those treated as offenders is not clear, and
      there is a lack of evidence about treatment effectiveness. AIMS: To test between
      group differences in aggression and treatment outcome in people with learning
      disability and challenging behaviour, with and without a forensic history.
      METHOD: Clinical records of 86 former in-patients (45 offenders and 41 non
      offenders) of a specialist unit were compared on measures of behavioural
      disturbance and placement outcome. RESULTS: People in the offenders group were
      significantly less likely to be aggressive to others and to use weapons, but
      significantly more likely to harm themselves compared with the non-offenders
      group. Both groups had a significant reduction in their challenging behaviour
      during admission, and there was no significant difference in treatment outcome.
      CONCLUSIONS: The negative reputation of people with learning disabilities who
      offend needs to be reconsidered.

PMID- 15572742
TI  - Factor structure in the Camberwell Assessment of Need.
AB  - BACKGROUND: In order to define needs for care of people with severe mental
      illness, the Camberwell Assessment of Need (CAN) is focused on measuring personal
      and social functioning. However, previous studies of the CAN have given
      inconsistent results in terms of what variables are actually being measured.
      AIMS: To investigate the factor structure of the CAN. METHOD: Assessments of 741
      out-patients (mean age 45.5 years, 50% females) with severe mental illness (68%
      schizophrenia or other psychotic disorder) were used in an exploratory maximum
      likelihood factor analysis. RESULTS: Support was found for a three-factor model,
      comprising 13 of the 22 variables in the CAN, with the factors corresponding to
      functional disability (7 variables), social loneliness (3 variables) and
      emotional loneliness (3 variables). The remaining variables did not load on any
      factor. CONCLUSIONS: Exploratory factor analysis revealed three homogeneous
      dimensions in the CAN that may represent functional disability and two aspects of
      social health.

PMID- 15572743
TI  - Meeting the unmet need for depression services with psycho-educational self
      confidence workshops: preliminary report.
AB  - BACKGROUND: The prevalence of depression has not fallen despite effective
      treatments being available. AIMS: To examine the effectiveness of a psycho
      educational intervention designed to be easily accessible. METHOD: Large-scale,
      self-referral 'How to improve your self-confidence' workshops were run in a
      leisure centre at weekends. The day-long programme used a cognitive-behavioural
      approach. A randomised controlled trial design using waiting-list controls was
      employed. Three months after the workshop, results of workshop participants were
      compared with those of the waiting list control group. RESULTS: Among 120 people
      who self-referred, 75% of participants had General Health Questionnaire scores of
      3 and above. Over 39% had never previously consulted their general practitioners
      about their depression. At 3-month follow-up, members of the experimental group
      were significantly less depressed, less distressed and reported higher self
      esteem. CONCLUSIONS: Workshops were shown to be accessible and effective; a
      larger, more rigorous trial is now needed.

PMID- 15572744
TI  - Temporal course of auditory hallucinations.
AB  - We used functional magnetic resonance imaging to examine how brain activity
      associated with auditory verbal hallucinations in schizophrenia changed during
      hallucinatory events. Activation in the left inferior frontal and right middle
      temporal gyri was evident 6-9 s before the person signalled the onset of the
      hallucination, whereas activation in the bilateral temporal gyri and the left
      insula coincided with the perception of the hallucination. This supports the
      hypothesis that during hallucinations activation in cortical regions mediating
      the generation of inner speech may precede the engagement of areas implicated in
      the perception of auditory verbal material.

PMID- 15572745
TI  - Depression and the CIDI.

PMID- 15572746
TI  - Psychosocial factors in the pathogenesis of mental disorders.

PMID- 15572747
TI  - Learning disability services.

PMID- 15572749
TI  - Reflections on the landmark studies of beta-carotene supplementation.

PMID- 15572750
TI  - Defining the role of raloxifene for the prevention of breast cancer.

PMID- 15572751
TI  - Vioxx withdrawal alarms cancer prevention researchers.

PMID- 15572752
TI  - Corporations flock to selling for the (breast cancer) cure.

PMID- 15572753
TI  - Privacy regulations have mixed impact on cancer research community.

PMID- 15572754
TI  - License to test cancer vaccines in U.S. a victory for Cuban biotechnology.

PMID- 15572755
TI  - Stat bite: Frequency of cervical cancer screening by health plan, 2000-2003.

PMID- 15572756
TI  - The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and
      cardiovascular disease mortality during 6-year follow-up after stopping beta
      carotene and retinol supplements.
AB  - BACKGROUND: The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the
      effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the
      incidence of lung cancer, other cancers, and death in 18,314 participants who
      were at high risk for lung cancer because of a history of smoking or asbestos
      exposure. CARET was stopped ahead of schedule in January 1996 because
      participants who were randomly assigned to receive the active intervention were
      found to have a 28% increase in incidence of lung cancer, a 17% increase in
      incidence of death and a higher rate of cardiovascular disease mortality compared
      with participants in the placebo group. METHODS: After the intervention ended,
      CARET participants returned the study vitamins to their study center and provided
      a final blood sample. They continue to be followed annually by telephone and mail
      self-report. Self-reported cancer endpoints were confirmed by review of pathology
      reports, and death endpoints were confirmed by review of death certificates. All
      statistical tests were two-sided. RESULTS: With follow-up through December 31,
      2001, the post-intervention relative risks of lung cancer and all-cause mortality
      for the active intervention group compared with the placebo group were 1.12 (95%
      confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17),
      respectively. Smoothed relative risk curves for lung cancer incidence and all
      cause mortality indicated that relative risks remained above 1.0 throughout the
      post-intervention follow-up. By contrast, the relative risk of cardiovascular
      disease mortality decreased rapidly to 1.0 after the intervention was stopped.
      During the post-intervention phase, females had larger relative risks of lung
      cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality
      (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001)
      than males. CONCLUSIONS: The previously reported adverse effects of beta-carotene
      and retinyl palmitate on lung cancer incidence and all-cause mortality in
      cigarette smokers and individuals with occupational exposure to asbestos
      persisted after drug administration was stopped although they are no longer
      statistically significant. Planned subgroup analyses suggest that the excess
      risks of lung cancer were restricted primarily to females, and cardiovascular
      disease mortality primarily to females and to former smokers.

PMID- 15572757
TI  - Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal
      osteoporotic women in a randomized trial of raloxifene.
AB  - BACKGROUND: The randomized, double-blind Multiple Outcomes of Raloxifene
      Evaluation (MORE) trial found that 4 years of raloxifene therapy decreased the
      incidence of invasive breast cancer among postmenopausal women with osteoporosis
      by 72% compared with placebo. We conducted the Continuing Outcomes Relevant to
      Evista (CORE) trial to examine the effect of 4 additional years of raloxifene
      therapy on the incidence of invasive breast cancer in women in MORE who agreed to
      continue in CORE. METHODS: Women who had been randomly assigned to receive
      raloxifene (either 60 or 120 mg/day) in MORE were assigned to receive raloxifene
      (60 mg/day) in CORE (n = 3510), and women who had been assigned to receive
      placebo in MORE continued on placebo in CORE (n = 1703). Breast cancer incidence
      was analyzed by a log-rank test, and a Cox proportional hazards model was used to
      compute hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical
      tests were two-sided. RESULTS: During the CORE trial, the 4-year incidences of
      invasive breast cancer and estrogen receptor (ER)-positive invasive breast cancer
      were reduced by 59% (HR = 0.41; 95% CI = 0.24 to 0.71) and 66% (HR = 0.34; 95% CI
      = 0.18 to 0.66), respectively, in the raloxifene group compared with the placebo
      group. There was no difference between the two groups in incidence of ER-negative
      invasive breast cancer during CORE (P = .86). Over the 8 years of both trials,
      the incidences of invasive breast cancer and ER-positive invasive breast cancer
      were reduced by 66% (HR = 0.34; 95% CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI
      = 0.15 to 0.40), respectively, in the raloxifene group compared with the placebo
      group. During the CORE trial, the relative risk of thromboembolism in the
      raloxifene group compared with that in the placebo group was 2.17 (95% CI = 0.83
      to 5.70). This increased risk, also observed in the MORE trial, persisted over
      the 8 years of both trials. CONCLUSIONS: The reduction in invasive breast cancer
      incidence continues beyond 4 years of raloxifene treatment in postmenopausal
      women with osteoporosis. No new safety concerns related to raloxifene therapy
      were identified during CORE.

PMID- 15572758
TI  - Contralateral breast cancer and thromboembolic events in African American women
      treated with tamoxifen.
AB  - BACKGROUND: Information about breast cancer treatment and prevention in African
      American women is scant, and recommendations for therapy from clinical trials for
      breast cancer are based primarily on data obtained from white women. METHODS: We
      compared the effects of tamoxifen on risk of contralateral breast cancer and
      thromboembolic events in African American women and white women with a history of
      primary breast cancer. Data from 13 National Surgical Adjuvant Breast and Bowel
      Project clinical trials were pooled for analyses of time to contralateral breast
      cancer as a first event (eight trials and 10,619 patients) and of time to any
      thromboembolic phenomenon as a first event (all 13 trials and 20,878 patients).
      Risk factors for contralateral breast cancer and thromboembolic events among all
      women were determined using univariate proportional hazards models. (For each
      racial group, the rate of events associated with tamoxifen use was calculated as
      the ratio of the incidence rate with tamoxifen to that without tamoxifen.)
      Proportional hazards regression models were used to calculate 95% confidence
      intervals (CIs) and risk ratios. All statistical tests were two-sided. RESULTS:
      Risk factors for contralateral breast cancer were body mass index (BMI) and lymph
      node positivity; those for thromboembolic events were BMI and age. In women of
      both ethnicities with estrogen receptor-positive breast cancer, those who took
      tamoxifen experienced a similar reduction in contralateral breast cancer (risk
      ratio for African American women = 0.74, 95% CI = 0.46 to 1.17, n = 690; risk
      ratio for white women = 0.76, 95% CI = 0.59 to 0.98, n = 9929; P = .92).
      Tamoxifen was also associated with an increase in thromboembolic events. The
      relative risk for thromboembolic events was higher in both African American and
      white women treated with tamoxifen and chemotherapy than in those who were
      treated with tamoxifen alone (risk ratio for African American women = 10.70, 95%
      CI = 5.94 to 19.28 versus 2.16, 95% CI = 1.26 to 3.71; n = 1842; risk ratio for
      white women = 15.49, 95% CI = 9.53 to 25.17 versus 3.13, 95% CI = 2.04 to 4.79, n
      = 19,036), and this effect was similar between the races (P = .10). CONCLUSIONS:
      African American and white women appear to have the same risks of contralateral
      breast cancer and thromboembolic events in response to tamoxifen treatment.

PMID- 15572759
TI  - Death receptor regulation and celecoxib-induced apoptosis in human lung cancer
      cells.
AB  - BACKGROUND: Celecoxib, a cyclooxygenase 2 inhibitor, has chemopreventive and
      therapeutic activities toward lung cancer and other epithelial malignancies.
      Celecoxib can induce apoptosis in various cancer cell lines through a mechanism
      that is independent of its cyclooxygenase 2 inhibitory activity but is otherwise
      largely uncharacterized. We investigated the mechanism of celecoxib-induced
      apoptosis further. METHODS: All experiments were conducted in human non-small
      cell lung carcinoma (NSCLC) cell lines; results in celecoxib-treated and
      untreated cells were compared. Cell survival was assessed with a sulforhodamine B
      assay. Apoptosis was assessed by DNA fragmentation with an enzyme-linked
      immunosorbent assay, by terminal deoxynucleotidyltransferase-mediated dUTP nick
      end-labeling (TUNEL) assay, and by western blot analysis of caspase activation.
      Death receptor gene and protein expression was detected by northern and western
      blot analysis, respectively. Gene silencing was achieved with small interfering
      RNA (siRNA) technology. RESULTS: Celecoxib treatment decreased cell survival,
      activated caspase cascades, and increased DNA fragmentation, all of which were
      abrogated when caspase 8 expression was silenced with caspase 8 siRNA. Celecoxib
      treatment induced the expression of death receptors, particularly that of DR5.
      Overexpression of a dominant negative Fas-associated death domain mutant, but not
      of BCL2, reduced the level of celecoxib-induced apoptosis, and silencing of DR5
      expression by DR5 siRNA suppressed celecoxib-induced caspase 8 activation and
      apoptosis. Combination treatment with celecoxib and tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) induced additional apoptosis. For example,
      survival of A549 cells was decreased with 50 muM celecoxib alone by 38.7% (95%
      confidence interval [CI] = 35.2% to 42.2%), with TRAIL alone by 29.3% (95% CI =
      25.1% to 33.6%), but with their combination by 77.5% (95% CI = 74.5% to 79.5%), a
      greater than additive effect. CONCLUSION: Celecoxib appears to induce apoptosis
      in human NSCLC through the extrinsic death receptor pathway.

PMID- 15572760
TI  - Cancer incidence among pesticide applicators exposed to chlorpyrifos in the
      Agricultural Health Study.
AB  - BACKGROUND: Chlorpyrifos is one of the most widely used insecticides in the
      United States. We evaluated the incidence of cancer among pesticide applicators
      exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort
      study of licensed pesticide applicators in Iowa and North Carolina. METHODS: A
      total of 54,383 pesticide applicators were included in this analysis. Detailed
      information on pesticide exposure and lifestyle factors was obtained from self
      administered questionnaires completed at the time of enrollment (December 1993
      December 1997). Poisson regression analysis was used to evaluate the association
      between chlorpyrifos exposure and cancer incidence after adjustment for potential
      confounders. All statistical tests were two-sided. RESULTS: A total of 2070
      incident malignant neoplasms were diagnosed through 2001. The rate ratio for all
      cancers combined among chlorpyrifos-exposed applicators compared with nonexposed
      applicators was 0.97 (95% confidence interval = 0.87 to 1.08). For most cancers
      analyzed, there was no evidence of an exposure-response relationship. However,
      the incidence of lung cancer was statistically significantly associated with both
      chlorpyrifos lifetime exposure-days (P(trend) = .002) and chlorpyrifos intensity
      weighted exposure-days (P(trend) = .036). After adjustment for other pesticide
      exposures and demographic factors, individuals in the highest quartile of
      chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer
      2.18 (95% confidence interval = 1.31 to 3.64) times that of those with no
      chlorpyrifos exposure. CONCLUSION: Our findings suggest an association between
      chlorpyrifos use and incidence of lung cancer that deserves further evaluation.

PMID- 15572761
TI  - Impaired processing of DNA photoproducts and ultraviolet hypermutability with
      loss of p16INK4a or p19ARF.
AB  - Reduced DNA repair has been linked to an increased risk of cutaneous malignant
      melanoma, but insights into the molecular mechanisms of that link are scarce. The
      INK4a/ARF (CDKN2a) locus, which codes for the p16(INK4a) and p19ARF proteins, is
      often mutated in sporadic and familial malignant melanoma, but it has not been
      directly associated with reduced DNA repair. We transfected unirradiated mouse
      fibroblast cells with UV-treated DNA to measure DNA repair in normal, p16INK4a
      mutant, p19ARF mutant, or double mutant mouse host cells. Loss of either
      p16(INK4a) or p19ARF reduced the ability of the cells to process UV-induced DNA
      damage, independent of cell cycle effects incurred by the loss. These results may
      further explain why INK4a/ARF mutations predispose to malignant melanoma, a UV
      induced tumor.

PMID- 15572762
TI  - Re: Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of
      NSABP protocol C-01.

PMID- 15572763
TI  - Re: Akt phosphorylation and gefitinib efficacy in patients with advanced non
      small-cell lung cancer.

PMID- 15572764
TI  - Interactive electron-density map interpretation: from INTER to O.
AB  - A short review of the author's computer-graphics developments since 1976 is
      presented. Some of the major developments in these programs are reviewed and a
      description is provided of some of the more recent tools that can be used for
      electron-density map interpretation. These tools include a secondary-structure
      template-building system that works in conjunction with a new sequence-decoration
      system.

PMID- 15572765
TI  - Coot: model-building tools for molecular graphics.
AB  - CCP4mg is a project that aims to provide a general-purpose tool for structural
      biologists, providing tools for X-ray structure solution, structure comparison
      and analysis, and publication-quality graphics. The map-fitting tools are
      available as a stand-alone package, distributed as 'Coot'.

PMID- 15572766
TI  - Statistical pattern recognition for macromolecular crystallographers.
AB  - A selection of pattern-recognition techniques is presented with a special focus
      on those methods that may be of interest to macromolecular crystallographers not
      indifferent to automated protein model building. An overview of the most common
      pattern-recognition approaches is given and some popular model-building packages
      are briefly reviewed within this context.

PMID- 15572767
TI  - Using prime-and-switch phasing to reduce model bias in molecular replacement.
AB  - Atomic models are commonly used to calculate phases in macromolecular
      crystallography. When combined with measured amplitudes, model-based phases yield
      electron-density maps with features of the correct structure but with a
      significant bias towards features of the model. The present contribution shows
      applications of the technique of prime-and-switch phasing to reduce this bias. An
      atomic model is used to generate phases that are close to the correct set but
      that may be biased. An unbiased source of phase information, an estimate of the
      probability that the electron-density map corresponds to a macromolecule, is then
      used to select a set of phases that are near the biased set, without further
      reference to the biased phases. The probability that the electron-density map
      corresponds to a macromolecule is based on agreement of the map with expectations
      such as a flat solvent region. Prime-and-switch phasing can be useful even for
      crystals with low solvent content and may reduce errors in interpretation of
      electron density in a wide range of applications of macromolecular
      crystallography, including molecular replacement, model building, ligand-binding
      and conformation-change studies, refinement and structure validation.

PMID- 15572768
TI  - Practical aspects of the integration of different software in protein structure
      solution.
AB  - There is presently an increasing variety of choice in the software for
      macromolecular phasing and automated model building. In addition to its positive
      features, this variety poses the problem of which software to use in a specific
      crystallographic case. Moreover, it must be decided whether a sequence of
      programs should be used to achieve structure solution more accurately and more
      rapidly, taking into account the features of the different programs: some
      software is more suitable for dealing with low-symmetry rather than high-symmetry
      space groups in the detection of heavy-atom sites, while others can give better
      estimates of the figures of merit on phases in certain cases (which is crucial in
      dealing with maximum likelihood) and others are more suitable for chain tracing
      at low/medium-low resolution than at high resolution or vice versa. The
      'integrated' choice of different software has become popular among
      crystallographers, especially when facing crystallographic cases that are not
      straightforward. A few examples will be presented on the use of different
      programs to achieve the goal of structure solution and the associated
      practicalities that can make the difference between solving or not solving a
      structure.

PMID- 15572769
TI  - Introduction to macromolecular refinement.
AB  - The process of refinement is such a large problem in function minimization that
      even the computers of today cannot perform the calculations to properly fit X-ray
      diffraction data. Each of the refinement packages currently under development
      reduces the difficulty of this problem by utilizing a unique combination of
      targets, assumptions and optimization methods. This review summarizes the basic
      methods and underlying assumptions in the commonly used refinement packages. This
      information can guide the selection of a refinement package that is best suited
      for a particular refinement project.

PMID- 15572770
TI  - Liking likelihood.
AB  - Maximum-likelihood methods have now been applied to most areas of macromolecular
      crystallography, including data reduction, molecular replacement, experimental
      phasing and refinement. However, students of macromolecular crystallography are
      predominantly taught only traditional crystallographic methods and therefore have
      little understanding of the methods underlying the modern software that they
      routinely use in structure determination. This situation arises, at least in
      part, because maximum likelihood is considered to be too difficult to be taught
      to students who lack substantial mathematical training within the limited time
      frame of undergraduate/graduate courses. A method of introducing maximum
      likelihood concepts with the help of dice is described here and it is then shown
      how these concepts can form the core of understanding maximum-likelihood
      refinement, molecular replacement and experimental phasing. Within the framework
      described, the crystallographic maximum-likelihood techniques are all reduced to
      the same basic concepts and become easier and less time-consuming to teach than
      traditional methods, which rely on disparate concepts.

PMID- 15572771
TI  - REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for
      its use.
AB  - One of the most important aspects of macromolecular structure refinement is the
      use of prior chemical knowledge. Bond lengths, bond angles and other chemical
      properties are used in restrained refinement as subsidiary conditions. This
      contribution describes the organization and some aspects of the use of the
      flexible and human/machine-readable dictionary of prior chemical knowledge used
      by the maximum-likelihood macromolecular-refinement program REFMAC5. The
      dictionary stores information about monomers which represent the constitutive
      building blocks of biological macromolecules (amino acids, nucleic acids and
      saccharides) and about numerous organic/inorganic compounds commonly found in
      macromolecular crystallography. It also describes the modifications the building
      blocks undergo as a result of chemical reactions and the links required for
      polymer formation. More than 2000 monomer entries, 100 modification entries and
      200 link entries are currently available. Algorithms and tools for updating and
      adding new entries to the dictionary have also been developed and are presented
      here. In many cases, the REFMAC5 dictionary allows entirely automatic generation
      of restraints within REFMAC5 refinement runs.

PMID- 15572772
TI  - Direct incorporation of experimental phase information in model refinement.
AB  - The incorporation of prior phase information into a maximum-likelihood formalism
      has been shown to strengthen model refinement. However, the currently available
      likelihood refinement target using prior phase information has shortcomings; the
      'phased' refinement target considers experimental phase information indirectly
      and statically in the form of Hendrickson-Lattman coefficients. Furthermore, the
      current refinement target implicitly assumes that the prior phase information is
      independent of the calculated model structure factor. This paper describes the
      derivation of a multivariate likelihood function that overcomes these
      shortcomings and directly incorporates experimental phase information from a
      single-wavelength anomalous diffraction (SAD) experiment. This function, which
      simultaneously refines heavy-atom and model parameters, has been implemented in
      the refinement program REFMAC5. The SAD function used in conjunction with the
      automated model-building procedures of ARP/wARP leads to a successful solution
      when current likelihood functions fail in a test case shown.

PMID- 15572773
TI  - The potentials of conditional optimization in phasing and model building of
      protein crystal structures.
AB  - Model building is a pivotal step in protein-structure determination, because with
      an atomic model available the vast amount of geometrical prior knowledge may be
      applied to the structure-determination process. Here, conditional optimization, a
      method that does not require interpretation of the electron-density map, is
      described. Instead, this method refines loose atoms for which all chemical
      interpretations are considered simultaneously using an N-particle formalism. This
      method bears the potential of introducing the geometrical data much earlier in
      the structure-determination process, i.e. well before an interpretable electron
      density map has been obtained. Here, results from two tests are presented:
      automated model building of three proteins with diffraction data extending to 2.4
      3.0 A resolution and ab initio phasing of a small four-helical bundle with
      diffraction data to 2.0 A resolution. Models built automatically by the widely
      used programs ARP/wARP and RESOLVE and those from conditional optimization per
      se, without discrete modelling steps, had comparable phase quality and
      completeness, except in loop regions, which are poorly modelled by the current
      force field in conditional optimization. Optimization of multiple random starting
      models by conditional optimization yielded models revealing the four helices of
      the four-helical bundle.

PMID- 15572774
TI  - Refinement of severely incomplete structures with maximum likelihood in BUSTER
      TNT.
AB  - BUSTER-TNT is a maximum-likelihood macromolecular refinement package. BUSTER
      assembles the structural model, scales observed and calculated structure-factor
      amplitudes and computes the model likelihood, whilst TNT handles the
      stereochemistry and NCS restraints/constraints and shifts the atomic coordinates,
      B factors and occupancies. In real space, in addition to the traditional atomic
      and bulk-solvent models, BUSTER models the parts of the structure for which an
      atomic model is not yet available ('missing structure') as low-resolution
      probability distributions for the random positions of the missing atoms. In
      reciprocal space, the BUSTER structure-factor distribution in the complex plane
      is a two-dimensional Gaussian centred around the structure factor calculated from
      the atomic, bulk-solvent and missing-structure models. The errors associated with
      these three structural components are added to compute the overall spread of the
      Gaussian. When the atomic model is very incomplete, modelling of the missing
      structure and the consistency of the BUSTER statistical model help structure
      building and completion because (i) the accuracy of the overall scale factors is
      increased, (ii) the bias affecting atomic model refinement is reduced by
      accounting for some of the scattering from the missing structure, (iii) the
      addition of a spatial definition to the source of incompleteness improves on
      traditional Luzzati and sigmaA-based error models and (iv) the program can
      perform selective density modification in the regions of unbuilt structure alone.

PMID- 15572775
TI  - Towards complete validated models in the next generation of ARP/wARP.
AB  - The design of a new versatile control system that will underlie future releases
      of the automated model-building package ARP/wARP is presented. A sophisticated
      expert system is under development that will transform ARP/wARP from a very
      useful model-building aid to a truly automated package capable of delivering
      complete, well refined and validated models comparable in quality to the result
      of intensive manual checking, rebuilding, hypothesis testing, refinement and
      validation cycles of an experienced crystallographer. In addition to the
      presentation of this control system, recent advances, ideas and future plans for
      improving the current model-building algorithms, especially for completing
      partially built models, are presented. Furthermore, a concept for integrating
      validation routines into the iterative model-building process is also presented.

PMID- 15572776
TI  - Modelling bound ligands in protein crystal structures.
AB  - Methods for automated identification and building of protein-bound ligands in
      electron-density maps are described. An error model of the geometrical features
      of the molecular structure of a ligand based on a lattice distribution of
      positional parameters is obtained via simulation and is used for the construction
      of an approximate likelihood scoring function. This scoring function combined
      with a graph-based search technique provides a flexible model-building scheme and
      its application shows promising initial results. Several ligands with sizes
      ranging from 9 to 44 non-H atoms have been identified in various X-ray structures
      and built in an automatic way using a minimal amount of prior stereochemical
      knowledge.

PMID- 15572777
TI  - The Uppsala Electron-Density Server.
AB  - The Uppsala Electron Density Server (EDS; http://eds.bmc.uu.se/) is a web-based
      facility that provides access to electron-density maps and statistics concerning
      the fit of crystal structures and their maps. Maps are available for
      approximately 87% of the crystallographic Protein Data Bank (PDB) entries for
      which structure factors have been deposited and for which straightforward map
      calculations succeed in reproducing the published R value to within five
      percentage points. Here, an account is provided of the methods that are used to
      generate the information contained in the server. Some of the problems that are
      encountered in the map-generation process as well as some spin-offs of the
      project are also discussed.

PMID- 15572778
TI  - The new CCP4 Coordinate Library as a toolkit for the design of coordinate-related
      applications in protein crystallography.
AB  - The new CCP4 Coordinate Library is a development aiming to provide a common layer
      of coordinate-related functionality to the existing applications in the CCP4
      suite, as well as a variety of tools that can simplify the design of new
      applications where they relate to atomic coordinates. The Library comprises a
      wide spectrum of useful functions, ranging from parsing coordinate formats and
      elementary editing operations on the coordinate hierarchy of biomolecules, to
      high-level functionality such as calculation of secondary structure, interatomic
      bonds, atomic contacts, symmetry transformations, structure superposition and
      many others. Most of the functions are available in a C++ object interface;
      however, a Fortran interface is provided for compatibility with older CCP4
      applications. The paper describes the general principles of the Library design
      and the most important functionality. The Library, together with documentation,
      is available under the LGPL license from the CCP4 suite version 5.0 and higher.

PMID- 15572779
TI  - Secondary-structure matching (SSM), a new tool for fast protein structure
      alignment in three dimensions.
AB  - The present paper describes the SSM algorithm of protein structure comparison in
      three dimensions, which includes an original procedure of matching graphs built
      on the protein's secondary-structure elements, followed by an iterative three
      dimensional alignment of protein backbone Calpha atoms. The SSM results are
      compared with those obtained from other protein comparison servers, and the
      advantages and disadvantages of different scores that are used for structure
      recognition are discussed. A new score, balancing the r.m.s.d. and alignment
      length Nalign, is proposed. It is found that different servers agree reasonably
      well on the new score, while showing considerable differences in r.m.s.d. and
      Nalign.

PMID- 15572780
TI  - Domain identification by iterative analysis of error-scaled difference distance
      matrices.
AB  - Iterative interpretation of error-scaled difference distance matrices is
      suggested as a means of dividing a protein into structural domains on the basis
      of conformational differences between different models. Two conformers of Src
      kinase [PDB codes 1fmk [Xu et al. (1997). Nature (London), 385, 595-602] and 2src
      [Xu et al. (1999). Mol. Cell, 3, 629-638]] in the inactive state with and without
      a substrate analogue bound are analysed in order to demonstrate the approach.
      SH3, SH2 and the N- and C-terminal lobes of the kinase domain are detected as
      structural modules that move with respect to each other. Notably, a relative
      movement between the SH3 and SH2 domains is detected although both structures of
      Src kinase are in the 'assembled' state. Detailed analysis shows that Arg318, a
      residue topologically located in the N-terminal lobe of the kinase domain,
      structurally belongs to the C-terminal lobe. The movement of this residue
      together with the C-terminal lobe upon substrate binding leads to the loss of a
      salt bridge between Arg318 and Asp117, a residue in the SH3 domain, providing an
      explanation for the increased mobility of the SH3 domain.

PMID- 15572781
TI  - Differential evolution for protein crystallographic optimizations.
AB  - Genetic algorithms are powerful optimizers that have been underutilized in
      protein crystallography, given that many crystallographic problems have
      characteristics that would benefit from these algorithms: non-linearity,
      interdependent parameters and a complex function landscape. These functions have
      been implemented for real-space optimizations in a new fitting program, MIfit,
      for real-space refinement of protein models and heavy-atom searches. Some
      programming tips and examples will be presented here to aid others who might want
      to use genetic algorithms in their own work.

PMID- 15572782
TI  - Dynamite: a simple way to gain insight into protein motions.
AB  - A public web-based facility to infer, analyse and graphically represent the
      likely modes of a protein motion, starting from a static structure, is presented.
      This facility is based on the use of CONCOORD to generate an ensemble of feasible
      protein structures that are subsequently analysed by principal component analysis
      to identify probable concerted motions. The user is returned the ensemble of
      feasible structures, together with associated analyses, including animations and
      graphical representations of both the principal component of the ensemble
      covariance and indicators of strongly correlated pairwise atomic motions. Whilst
      users are warned that completely reliable inferences about protein motion may be
      beyond even substantially more rigorous tools for exploring configurational
      space, it is hoped that the service will allow a much wider community to benefit
      from the insights that simple dynamic data may offer.

PMID- 15572783
TI  - Developments in the CCP4 molecular-graphics project.
AB  - Progress towards structure determination that is both high-throughput and high
      value is dependent on the development of integrated and automatic tools for
      electron-density map interpretation and for the analysis of the resulting atomic
      models. Advances in map-interpretation algorithms are extending the resolution
      regime in which fully automatic tools can work reliably, but at present human
      intervention is required to interpret poor regions of macromolecular electron
      density, particularly where crystallographic data is only available to modest
      resolution [for example, I/sigma(I) < 2.0 for minimum resolution 2.5 A]. In such
      cases, a set of manual and semi-manual model-building molecular-graphics tools is
      needed. At the same time, converting the knowledge encapsulated in a molecular
      structure into understanding is dependent upon visualization tools, which must be
      able to communicate that understanding to others by means of both static and
      dynamic representations. CCP4 mg is a program designed to meet these needs in a
      way that is closely integrated with the ongoing development of CCP4 as a program
      suite suitable for both low- and high-intervention computational structural
      biology. As well as providing a carefully designed user interface to advanced
      algorithms of model building and analysis, CCP4 mg is intended to present a
      graphical toolkit to developers of novel algorithms in these fields.

PMID- 15572812
TI  - Comparison of terbutaline and salbutamol inhalation in children with mild or
      moderate acute exacerbation of asthma.
AB  - OBJECTIVE: To compare the clinical efficacy and side effects of terbutaline and
      salbutamol administered by metered dose inhaler and holding chamber in the mild
      to moderate acute exacerbations of asthma in children. METHODS: The study
      subjects were children in the age group of 5- 15 years who presented with a mild
      or moderate acute exacerbation of asthma. Baseline assessment included clinical
      parameters and spirometry. The children were then randomized to receive
      salbutamol or terbutaline. Three puffs each of either 100 mcg salbutamol or 250
      mcg of terbutaline were administered using 750 ml holding chamber with valve.
      Thirty minutes after drug administration, the children were reevaluated for
      clinical parameters and spirometry. RESULTS: Of the total 60 subjects studied, 31
      were administered terbutaline and 29 salbutamol. The baseline spirometric
      parameters were comparable. After drug administration, all the studied variables
      showed significant improvement within each group. However, there were no
      statistically significant differences when the two groups were compared with each
      other. There was no significant difference in the side effects between two
      groups. CONCLUSION: Terbutaline and salbutamol, when administered by MDI with
      holding chamber, are equally efficacious in children with mild or moderate acute
      exacerbation of asthma.

PMID- 15572813
TI  - Age-specific prevalence of hepatitis B surface antigen in pediatric population of
      Aligarh, North India.
AB  - OBJECTIVE: To estimate the age-specific seroprevalence of hepatitis B surface
      antigen (HBsAg) in children upto 14 years of age. METHODS: Equal number (115
      each) of apparently healthy children of both sexes of different age groups i.e. <
      1, 1-4, 5-9 and 10-14 years, attending pediatric outpatient services and Well
      Baby Clinic of the hospital were tested for HBsAg using ELISA test. Positive
      results were confirmed by a second ELISA. RESULTS: Overall 4.35% (95%CI, 2.44 -
      6.25) of the 460 children tested were HBsAg positive. The prevalence rate was the
      highest (6.09%) in the 1-4 year age category. In the < 1, 5-9 and 10-14 year age
      groups it was 4.35%, 4.35% and 2.61% respectively. The overall male to female
      ratio was 2.1:1, with no significant difference in seropositivity rates (P =
      0.816). The difference in the prevalence rates between the rural (4.84%) and
      urban populations (3.77%) was also statistically insignificant (P = 0.577).
      CONCLUSION: Average HBsAg positivity in the pediatric population in this region
      is 4.35% (95%CI, 2.44 - 6.25). The prevalence progressively increases and peaks
      in the 1- 4 years age group. It is least in 10-14 years age group.

PMID- 15572814
TI  - Comparison of two antibiotic regimens in the empirical treatment of severe
      childhood pneumonia.
AB  - OBJECTIVE: The diagnosis and the treatment of community-acquired severe pneumonia
      is still a serious child health problem in developing countries. The aim of this
      study is to evaluate the effectiveness of two different antibiotic regimens in
      the empirical treatment of severe childhood pneumonia. METHODOLOGY: We enrolled
      97 infants (aged 2-24 months) with severe community-acquired pneumonia in a
      randomized-controlled trial of 10 days of treatment with penicillin
      G+chloramphenicol (n:46) or ceftriaxone (n:51). We evaluated the effectiveness of
      treatments with symptoms and some laboratory tests during and at the end of the
      study. RESULTS: The cure rates were similar in both groups and the antibiotic
      regimens in all patients were found effective (P< 0.001). The number of nurse
      rounds was much more in penicillin plus chloramphenicol group than ceftriaxone
      group. CONCLUSION: Both penicillin G plus chloramphenicol and ceftriaxone are
      effective in the empirical treatment of severe community pneumonia of young
      children. In spite of more nurse visits for antibiotic treatment, penicillin G+
      chloramphenicol combination may be a cheaper alternative to ceftriaxone in the
      treatment of childhood pneumonia.

PMID- 15572815
TI  - Oral itraconazole in treatment of candidemia in a pediatric intensive care unit.
AB  - OBJECTIVE: To examine efficacy of itraconazole in the treatment of candidemia in
      critically ill children. METHODS: We studied retrospectively cases of candidemia
      seen consecutively in our Pediatric Intensive Care Unit (PICU) over three and
      half years. Candida isolates from those patients included. Candida albicans--19,
      C. tropicalis--31, C. guillermondii--9, C.krusei--4 and C. glabrata--1. RESULTS:
      Of the 64 patients, 48 (75%) had symptoms suggestive of septicemia and 16 had no
      symptoms suggestive of septicemia. No antifungal therapy was given to
      asymptomatic patients; they recovered from candidemia without development of any
      sequelae. Of the 48 symptomatic patients 11 died before results of fungal culture
      became available and antifungal therapy could be started. Thirty seven patients
      were treated with itraconazole (10 mg/kg/day orally or through gastric tube).
      Seven (18.9 %) of 37 patients died, 3 within first week of antifungal therapy.
      Thirty (81%) patients recovered; microbiological cure was noted on average by day
      14 (range 4-30 days). The mean +/- SD duration of therapy in patients who
      responded was 24 +/-7 days (range 21-42 days). None had any major side effect.
      CONCLUSION: We conclude that oral itraconazole may be effective in treatment of
      candidemia in children in a PICU where non-C. albicans candida species
      constituted majority (70%) of all Candida isolates.

PMID- 15572816
TI  - Intramuscular antibiotic treatment of urinary tract infection.
AB  - OBJECTIVE: This study had been carried out to investigate the effects of
      intramuscular daily single dose antibiotic treatment during five days in the
      outpatient clinics in children having lower UTI and to observe the effects to the
      disease course in infants and toddlers. METHODOLOGY: 36 children (12 boys) at the
      ages of between 5-68 months were enrolled into the study. Regarding the
      antibiogram suitability, single dose ceftriaxon or amikacin is prescribed to the
      patients for five days. RESULT: In the urine cultures E. coli was most commonly
      isolated. There was correlation between leukocytosis and insufficient weight gain
      (p< 0.05). A correlation was also noted between recurrence of the disease and
      urinary tract abnormalities detected on the ultrasonography (p< 0.05). Re
      infections were detected in 1 of the infants and in 2 of the older children.
      There was no correlation between the recurrence and the therapy given.
      CONCLUSION: We consider that five-day intramuscular antibiotic therapy could be
      effective in the treatment of lower UTI and it can be recommended as a safe
      treatment modality in patients representing unwillingness to come to follow-up
      visits.

PMID- 15572817
TI  - Impact of single /multiple micronutrient supplementation on child health.

PMID- 15572818
TI  - Maternal micronutrients and fetal outcome.
AB  - Maternal micronutrient deficiency has been related to adverse fetal effects. It
      is believed that micronutrient supplementation during pregnancy may improve fetal
      and neonatal outcome. Despite biological plausibility, the evidence base for
      individual micronutrient benefit on neonatal morbidity, mortality, growth and
      development is patchy and often contradictory, except for the role of folic acid
      in prevention of neural tube defects. Single micronutrient supplementation
      interventions have not been shown to consistently affect size at birth or
      duration of gestation. Sound evidence is generally lacking that micronutrient
      supplementation can reduce infection-related adverse pregnancy outcomes. However,
      preliminary data suggests that antenatal zinc supplements may cause reduction in
      later diarrheal and infectious morbidity in infants. The evidence linking
      maternal micronutrient deficiency to children's cognitive and motor functioning
      also lacks a clear consensus except for iodine in endemic areas. There is a
      pressing need for good quality randomized controlled trials evaluating food based
      and multiple micronutrient interventions in pregnancy and preconceptually. Future
      studies should also evaluate the effect on body composition and metabolism along
      with the functional consequences.

PMID- 15572819
TI  - Zinc in child health and disease.
AB  - Zinc deficiency is common in children from developing countries due to lack of
      intake of animal foods, high dietary phytate content, inadequate food intake and
      increased fecal losses during diarrhea. Zinc has a fundamental role in cellular
      metabolism, with profound effects on the immune system and the intestinal mucosa.
      Zinc supplementation has shown significant benefits in prevention and treatment
      of diarrhea and pneumonia. Routine zinc supplementation given to low birth weight
      babies for a year has resulted in substantial reduction in mortality. Zinc
      deficiency may have adverse effects on physical growth and neurodevelopment. WHO
      Task Force, 2001, and the National task Force of IAP has recommended use of zinc
      in the treatment of diarrhea. It is also recommended as part of standard case
      management in persistent diarrhea and in those with severe malnutrition. Further
      evidence is required for qualifying its use in treatment of other infective
      diseases like pneumonia and malaria. Improved dietary quality & intake, food
      fortification and cultivation of zinc dense plants are some ways of mitigating
      zinc deficiency.

PMID- 15572820
TI  - Micronutrient fortification of foods--rationale, application and impact.
AB  - Deficiencies in intake of essential vitamins and minerals (commonly referred to
      as micronutrients) that are essential for efficient energy metabolism and other
      functions of the human body (commonly termed as micronutrients) are severe and
      widespread in many parts of the world. They cause an immeasurable burden on
      individuals, on health services, education systems and families caring for
      children who are disabled or mentally impaired. Studies by World Bank have shown
      that countries whose populations suffer from micronutrient deficiencies encounter
      economic losses as high as 5% of gross domestic product (GDP). The solution to
      control and prevent micronutrient deficiencies is available and affordable. At a
      national level, micronutrient malnutrition can be addressed by implementing
      programmes designed to educate people to diversify their diets (where appropriate
      foods are available), or by fortifying commonly eaten foods with the missing
      micronutrients or providing nutrient supplements through targeted distribution
      programmes. Food fortification is increasingly recognized as an effective means
      of delivering micronutrients. Fortification of foods can provide meaningful
      amounts of the nutrient at normal consumption of the food vehicle. Proper choice
      of fortificant and processing methods could ensure the stability and
      bioavailability of the nutrient. The level of fortification should take into
      account variations in food consumption to ensure safety for those at the higher
      end of the scale and impact for those at the lower end. Fortification needs to be
      supported by adequate food regulations and labeling, quality assurance and
      monitoring to ensure compliance and desired impact. In industrialized countries
      food fortification has played a major role in the substantial reduction and
      elimination of a number of micronutrient deficiencies. Although a growing number
      of large scale fortification programmes in different parts of the world are
      beginning to demonstrate impact at the biochemical level and are leading to the
      elimination of several nutrient deficiencies, food fortification remains an
      underutilized opportunity in many developing countries where micronutrient
      malnutrition remains a public health problem.

PMID- 15572821
TI  - Role of trace elements zinc, copper and magnesium during pregnancy and its
      outcome.
AB  - Trace element deficiencies have been documented to play an important role in
      determination of the fetal outcome. Pregnant women in developing countries have
      been reported to consume diets with a lower density of minerals and vitamins.
      Deficiencies of trace elements like zinc, copper and magnesium have been
      implicated in various reproductive events like infertility, pregnancy wastage,
      congenital anomalies, pregnancy induced hypertension, placental abruption,
      premature rupture of membranes, still births and low birth weight. The present
      review article highlights the important of role played by zinc, copper and
      magnesium during pregnancy and its outcome. The role of individual trace elements
      and in combination with other trace elements has not been completely documented.
      There is a need to undertake further studies in this field.

PMID- 15572822
TI  - Prevalence of multiple micronutrient deficiencies amongst pregnant women in a
      rural area of Haryana.
AB  - Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during
      pregnancy are known causes of Low Birth Weight (LBW). Studies have documented
      status of one or two micronutrients amongst pregnant women (PW). However, no
      attempt has been made to concurrently assess the prevalence of multiple
      micronutrient deficiencies and the factors associated with them amongst PW.
      OBJECTIVE: The present study was undertaken to assess the prevalence of multiple
      micronutrient deficiencies amongst PW in a rural area. METHODS: A community based
      cross sectional survey was conducted in six villages of a rural area of district
      Faridabad in Haryana state, India during November 2000 and October 2001. All PW
      aged 18 years or more, with pregnancy duration of more than 28 weeks were
      enrolled. Data were collected on socio-economic status and other demographic
      parameters. Serum zinc, copper and magnesium levels were estimated by utilizing
      the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was
      estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio
      Immuno Assay (RIA) method, respectively and serum thyroid stimulating hormone
      (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper,
      magnesium, ferritin, and folate levels less than 70.0 microg/dl, 80.0 microg/dl,
      1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of
      deficiency for respective micronutrients. The TSH levels of 4.670 and more
      indicated iodine deficiency status. Dietary intake of micronutrients was assessed
      utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was
      assessed utilizing the food frequency questionnaire methodology. RESULTS: Nearly
      73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper,
      magnesium, iron, folic acid and iodine, respectively. The highest concurrent
      prevalence of two, three, four and five micronutrient deficiency was of zinc and
      iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic
      acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%),
      respectively. No pregnant woman was found to have concomitant deficiencies of all
      the six micronutrients. Dietary intake data revealed an inadequate nutrient
      intake. Over 19% PW were consuming less than 50% of the recommended calories.
      Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than
      50% of the recommended folic acid, zinc, iron, copper, and magnesium. The
      consumption of food groups rich in micronutrients (pulses, vegetables, fruits,
      nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate
      logistic regression analysis revealed that low dietary intake of nutrients, low
      frequency of consumption of food groups rich in micronutrients and increased
      reproductive cycles with short interpregnancy intervals were important factors
      leading to micronutrient deficiencies. CONCLUSION: There was a high prevalence of
      micronutrient deficiencies amongst the PW of the area, possibly due to the poor
      dietary intake of food and low frequency of consumption of food groups rich in
      micronutrients. The concurrent prevalence of two, three, four and five
      micronutrient deficiencies were common.

PMID- 15572823
TI  - Controlling iron deficiency anemia through the use of home-fortified
      complementary foods.
AB  - Iron deficiency anemia (IDA) is more common in South Asian countries including
      India, Bangladesh and Pakistan than anywhere else in the world. During infancy
      and early childhood, IDA is associated with impaired psycho-motor development and
      cognitive function that may be irreversible. As a consequence, there is a growing
      awareness that IDA is one of many factors impeding socio-economic prosperity of
      developing nations. The combination of unacceptably high prevalence rates and
      inadequate preventative programs highlights the need for new effective
      sustainable strategies to control IDA. The burden of iron deficiency can be
      reduced by taking a more holistic approach that would include promotion of
      healthy weaning practices and use of appropriate complementary foods, together
      with improving the nutritional value of such foods. There is an increasing body
      of peer-reviewed literature to support the contention that "micronutrient
      Sprinkles" is an effective strategy to improve the nutritional value of home
      prepared complementary foods and thus to reduce the burden of iron deficiency
      among children. By combining data from recently conducted randomised control
      trials, Sprinkles were shown to be as efficacious as iron drops for treating
      childhood anemia. The iron in Sprinkles is well absorbed, and Sprinkles are easy
      to use and well accepted by young children and their caregivers. Integrated into
      existing public health programs, Sprinkles has the potential to improve the
      effectiveness of such programs.

PMID- 15572824
TI  - Central core disease.
AB  - Central core disease is a congenital myopathy characterized by generalized
      hypotonia, muscle weakness and presence of central cores on muscle biopsy. It
      generally presents during infancy. It is familial with autosomal dominant
      inheritance [Chromosome 19q13.1; Gene Locus RyR1 (Ryanodine receptor gene)]. We
      report here two cases of central core disease in a 3-year-old male child and 8
      year old female child.

PMID- 15572825
TI  - Drug induced hepatic focal nodular hyperplasia.
AB  - Focal nodular hyperplasia, an uncommon benign hepatic tumor, has been reported
      following ingestion of various drugs and chemical agents. The authors report a
      case of a young girl who developed such lesion following ingestion of anti
      tuberculosis drugs for the treatment of her abdominal tuberculosis.

PMID- 15572826
TI  - Leigh's syndrome.
AB  - A 15-month-old female child presented with sudden onset cough and
      hyperventilation along with evidence of metabolic acidosis. She had past history
      of recurrent vomiting, episodes of abnormal posturing, difficulty in deglutition
      and regression of milestones since 12 months of age. CT scan of the brain
      revealed hypodense lesions in bilateral basal ganglia and on MRI there were T2
      hyperintensities in bilateral lentiform nuclei, caudate nuclei, thalamus, red
      nuclei and dentate nuclei. Biochemical examination revealed persistently elevated
      serum lactate levels with high lactate/pyruvate ratio. Resuscitative measures
      were of no avail and the child succumbed to the illness on the second day of
      admission. Neuropathological examination at autopsy demonstrated marked
      spongiosis, focal necrosis, endothelial proliferation, reactive astrogliosis and
      extensive demyelination involving bilateral basal ganglia, midbrain and spinal
      cord which were typical of Leigh's sub acute necrotizing encephalomyelopathy.

PMID- 15572827
TI  - Acute disseminated encephalomyelitis.
AB  - The authors report 6 children with the diagnosis of acute disseminated
      encephalomyelitis. Diagnosis was based on clinical and radiological findings. The
      most common presenting symptoms were fever and disturbed consciousness, followed
      by cranial nerve abnormalities and pyramidal signs. Brain MRI showed hyperintense
      signals on T2-weighted images, most commonly in the subcortical and
      periventricular white matter, brainstem, basal ganglia and thalamus. The lesions
      were bilateral, asymmetrical and highly variable in size and number. A preceding
      infection was present in 3 of 6 children. Early high-dose corticosteroids were
      given to all the patients. All patients recovered clinically. Follow-up ranged
      from 10 months to 2 years. No relapses were observed during this period. Early
      high-dose steroid therapy seems to be an effective treatment in acute
      disseminated encephalomyelitis.

PMID- 15572828
TI  - Prevalence of infantile colic at a secondary level hospital.

PMID- 15572830
TI  - Controversies in BCG immunization.

PMID- 15572841
TI  - [Neurodegeneration caused by ER stress?--the pathogenetic mechanisms underlying
      AR-JP].
AB  - Mutations of the Parkin gene are responsible for autosomal recessive juvenile
      parkinsonism (AR-JP), the most common cause of early-onset familial Parkinson's
      disease. Parkin functions as an E3 ubiquitin ligase, thereby promoting
      ubiquitination and subsequent proteosomal degradation of its substrate(s). AR-JP
      is, therefore, thought to be caused by accumulation of an unknown toxic
      protein(s), which would normally be degraded by a molecular machinery involving
      Parkin. To date, ten different proteins are reported to be substrates of Parkin.
      Among these, a G protein-coupled orphan receptor called the Pael receptor (Pael
      R), which is highly expressed in dopaminergic neurons, attracts particular
      attention. When over-expressed in cells, the Pael-R protein became improperly
      folded and insoluble. Excessive accumulation of insoluble Pael-R led to
      endoplasmic reticulum (ER) stress-induced cell death. Parkin was observed to
      ubiquitinate the misfolded Pael-R protein, thereby promoting its degradation and
      suppressing misfolded Pael-R-induced cell death. Moreover, selective dopaminergic
      neurodegeneration was observed when human Pael-R was ectopically expressed in
      Drosophila brain, further supporting the idea that Pael-R accumulation plays a
      major role in AR-JP. In contrast, neither dopaminergic neurodegeneration nor
      accumulation of any known Parkin substrates was detected in Parkin knockout mice.
      The role of Pael-R in AR-JP will be discussed based on recent data.

PMID- 15572842
TI  - [The regulation of unfolded protein response by OASIS, a transmembrane bZIP
      transcription factor, in astrocytes].
AB  - The endoplasmic reticulum (ER) is susceptible to various stresses that provoke
      the accumulation of unfolded proteins in the ER. Excessive or long-termed
      stresses in the ER result in apoptotic cell death involving activation of caspase
      12 and -3 and the Ask-1-JNK pathway. Eukaryotic cells can adapt for survival to
      deal with an accumulation of unfolded proteins in the ER by increasing
      transcription of genes encoding ER-resident chaperones such as GRP78/BiP to
      facilitate protein folding. The induction system is termed the unfolded protein
      response (UPR). It has been reported that IRE1 and PERK, transmembrane kinases,
      and ATF6, a transmembrane transcription factor, are mediators of the UPR through
      sensing accumulation of unfolded proteins. Cell fates after ER stress are
      regulated by the balance of both apoptosis and the UPR signaling. In the nervous
      systems, astrocytes are well known to be resistant to ER stresses induced by
      ischemia and hypoxia. These findings raise the possibility that astrocytes
      possess a novel UPR signaling different from that of neuronal cells. Recently, we
      identified a novel ER stress sensor, OASIS, which is specifically expressed in
      astrocytes. This protein is a transmembrane protein containing the bZIP domain.
      The functional analyses of OASIS showed that 1) it was cleaved within the ER
      membrane in response to the ER stress, 2) overexpression of OASIS induced the
      transcription of GRP78/BiP mRNA through the activation of cyclic AMP responsive
      element (CRE) and ER stress responsive element (ERSE), and 3) its stable cell
      lines were resistant to ER stress compared with the control cells. These results
      indicate that the ER-resident transcription factor OASIS may be a candidate for
      leading astrocytes to protect against ER stress.

PMID- 15572843
TI  - [Protective effects of HRD1 and 4-phenylbutyric acid against neuronal cell
      death].
AB  - Endoplasmic reticulum-associated degradation (ERAD) is a system in which unfolded
      proteins drained from the ER lumen to the cytosol are ubiquitinated then degraded
      by 26S proteasome. We have identified and characterized human HRD1 as a ubiquitin
      ligase involved in ERAD that protects against ER stress-induced cell death.
      Accumulation of Pael receptor (Pael-R), a substrate of Parkin, has been proposed
      to lead to neuronal death in Autosomal Recessive Juvenile Parkinsonism (AR-JP).
      HRD1 co-localized with Pael-R in the ER and interacted with Pael-R through the
      proline-rich region of HRD1. HRD1 ubiquitinated and degraded Pael-R through its
      ubiqutin ligase activity. Furthermore, we found that ATF6 and XBP1 that induce
      HRD1 promoted the degradation of Pael-R. A class of compounds known as chemical
      chaperones, such as 4-phenylbutyric acid (4-PBA), has been demonstrated to repair
      unfolded proteins. We demonstrated that 4-PBA protected against ER stress-induced
      neuronal cell death. The tunicamycin-induced up-regulation of GRP78 and GRP94 and
      phosphorylation of PERK was suppressed by treatment with 4-PBA, indicating that 4
      PBA suppresses ER stress responses by decreasing unfolded protein. Furthermore, 4
      PBA suppressed ER stress induced by the overexpression of Pael-R. Thus, up
      regulation of HRD1 and 4-PBA could decrease accumulation of Pael-R.

PMID- 15572844
TI  - [NO-induced apoptosis and ER stress in microglia].
AB  - Nitric Oxide (NO) produced by activated microglia is an important contributor to
      neuronal damage. NO toxicity is generally thought to be mediated by the DNA
      damage-p53 pathway or mitochondrial dysfunction. We investigated the mechanism of
      NO toxicity by using microglial MG5 cells established from p53-deficient mouse.
      When MG5 cells were exposed to LPS plus IFN-gamma, mRNA and protein for inducible
      NO synthase (iNOS) were markedly induced and apoptosis occurred. Under these
      conditions, we found that mRNA and protein for CHOP/GADD153, a C/EBP family
      transcription factor that is involved in ER stress-induced apoptosis, were
      induced. These results suggest that NO-induced apoptosis in MG5 cells occurs
      through the ER stress pathway involving CHOP, but is independent of p53.
      Overactivation-induced apoptosis may be an essential self-regulatory mechanism
      for microglia in order to limit bystander killing of vulnerable neurons. On the
      other hand, recent reports suggest that there may exist two subtypes of microglia
      at least in the CNS. We found activated rat type-1 microglia induced expression
      of iNOS and exhibited neurotoxic to rat hippocampal neurons. By contrast,
      activated type-2 microglia hardly exhibited neurotoxicity in this co-culture
      system. These results suggest that the two subtype(s) of microglia may regulate
      differently the inflammatory response in the CNS.

PMID- 15572845
TI  - [Stress proteins and regulation of microglial amyloid-beta phagocytosis].
AB  - Recent studies have indicated that prolonged dysfunction and/or stress in the
      endoplasmic reticulum (ER) may contribute to pathogenesis and neurodegeneration.
      The disorder caused by misfolding and aggregation of proteins has been referred
      to as conformational disease, including Alzheimer's disease (AD). AD is
      characterized by the accumulation of extracellular amyloid-beta1-42 (A beta 42)
      fibrils with reactive microglia. Understanding the balance of production and
      clearance of A beta 42 is the key to elucidating amyloid plaque homeostasis. We
      have recently found that microglial phagocytosis of A beta 42 may be essentially
      driven by dynamic reorganization of the actin cytoskeleton through the pathway of
      WAVE and Rac1. In addition, an extracellular stress protein, such as Hsp90,
      enhances A beta 42 phagocytosis. HMGB1 inhibits microglial phagocytosis of A beta
      42, and it binds A beta 42 and stabilizes the oligomerization. These results
      suggest that microglial clearance of A beta 42 may be another option for
      investigations in the search for a therapeutic strategy for AD, in addition to
      the study of production and degradation of A beta 42.

PMID- 15572846
TI  - [Leukotriene-lipoxygenase pathway and drug discovery].
AB  - The first drugs affecting the leukotriene-lipoxygenase pathway, which have been
      introduced in clinical application, inhibit effects of slow reacting substance of
      anaphylaxis (SRS-A). Although, a 5-lipoxygenase inhibitor was first used in
      clinical practice as an anti-asthma drug, cysteinyl-leukotriene type 1 receptor
      (cysLT(1)R) antagonists are preferred as anti-asthma and anti-rhinitis drugs
      because they are almost as effective as the 5-lipoxygenase inhibitors but have
      fewer side effects. The cloning of genes related to lipoxygenase-leukotriene
      metabolism prompted us to try to elucidate the role of leukotrienes in various
      inflammations. There are at least two types of cysLTRs known: cysLT(1)R and
      cysLT(2)R. CysLT(1)R plays an important role in the pathophysiology of asthma;
      however, the role of the cysLT(2)R remains unknown. The abundant distribution of
      cysLT(2)R in heart and brain tissues suggests that cysLTs play an important role
      in the pathophysiology of ischemic heart diseases or arrhythmias and through this
      receptor (cysLT(2)R), psychoneurological disorders. The use of a selective
      cysLT(2)R antagonist may clarify these questions. Since the 5-lipoxygenase
      pathway is abundantly expressed in atherosclerotic lesions, and 12/15
      lipoxygenase is able to oxygenate polyunsaturated fatty acid esterified in the
      membranous phospholipids, 5-lipoxygenase or 12/15-lipoxygenase inhibitors may
      prevent progression of atherosclerosis. In addition, it has been reported that 15
      lipoxygenase participates in suppression of prostate cancer. In conclusion, the
      leukotriene-lipoxygenase metabolism may be involved in the pathophysiology of
      acute inflammatory to chronic progressive disorders. We think that more drugs
      modifying leukotriene-lipoxygenase metabolism will be introduced into clinical
      practice in the future.

PMID- 15572847
TI  - [Beta 2-adrenoceptor function in the kidney].
AB  - The majority of beta(2)-adrenoceptor (beta(2)-AR) agonists is eliminated via the
      kidneys as an unchanged substance. It is likely that such agents will exert
      pharmacological effects during their passage through the nephron. However, these
      pharmacological effects have, to our knowledge, not been taken into consideration
      when using these compounds in clinical practice because the role of beta(2)-AR in
      the regulation of renal function remains unclear. Renal beta(2)-ARs are
      predominantly localized to the proximal tubular epithelia and the membranes of
      smooth muscle cells from renal arteries. From this morphologic evidence, it is
      proposed that beta(2)-AR activation may regulate glomerular function and thereby
      sodium and water balance in the nephron segments. Actually, beta(2)-AR agonists
      given acutely cause a marked decrease in glomerular filtration rate. On the other
      hand, beta(2)-AR agonists inhibit the renal production of inflammatory cytokines
      such as TNF-alpha. Furthermore, the administration of beta(2)-AR agonists is
      found to attenuate apoptosis associated with shigatoxin in the hemolytic uremic
      syndrome (HUS). Increased understanding of the pharmacological basis of beta(2)
      AR function in the kidney provides important new information relevant to the
      clinical use of beta(2)-AR agonists in airway diseases and potential applications
      of these drugs in renal inflammation and injury associated with sepsis or HUS.

PMID- 15572848
TI  - [Preclinical and clinical profile of verteporfin, a potent photodynamic therapy
      drug for CNV secondary to AMD].
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness among
      people aged over 50 years in the western world. Verteporfin (Visudyne) is the
      first light-activated drug indicated for the treatment of patients with AMD
      caused by subfoveal choroidal neovascularization (CNV). This form of AMD is
      characterized by the development of abnormal blood vessels on the back of the
      retina that leak and cause scarring, resulting in central vision loss. Following
      intravenous administration, verteporfin selectively accumulates within
      proliferating tissue, including neovasculature, probably via low density
      lipoprotein receptors. The verteporfin is then activated by shining a specific
      wavelength of light with a nonthermal laser on the affected area in the eye. This
      process, called photodynamic therapy (PDT), generates reactive free radicals and
      highly reactive singlet oxygen in the target cells in the eye, causing damage and
      occlusion of the CNV and resulting in closure of the abnormal vessels and
      cessation of leakage. In experimentally induced CNV in animal models and in
      randomized, controlled clinical trials of patients with CNV due to AMD,
      verteporfin PDT has been shown to selectively occlude abnormal vessels without
      significantly altering overlying photoreceptors. Verteporfin therapy for CNV in
      Japanese patients had a similar or better angiographic and vision effect as that
      observed in Caucasian patients, with the same safety profile.

PMID- 15572849
TI  - Plasma leptin levels in rats with pancreatitis.
AB  - Diagnosis of pancreatitis is based on the determination of serum amylase and
      lipase levels. However, recent identification of specific leptin receptors in the
      pancreas suggests that this peptide may also play some roles in the modulation of
      pancreatic function. The objective of the present study was to investigate the
      relationship between serum leptin levels and pancreatitis. Thirty male Wistar
      rats were divided into 3 groups: the control group, acute pancreatitis group and
      chronic pancreatitis group. Pancreatitis was induced by injection of ethyl
      alcohol into the common biliary duct. A sham laparotomy was performed in the
      control group. Control and acute pancreatitis groups were sacrificed 24 hours
      later, and chronic pancreatitis group was sacrificed on postoperative day 7.
      Blood was taken by cardiac puncture for the determination of plasma leptin
      levels, and the pancreatic tissue was excised for histopathologic confirmation of
      pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12
      ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in
      acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There
      was no significant difference in the plasma leptin levels between the acute
      pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings
      confirm that leptin has a role in pancreas inflammation, and the inflamed tissue
      can be the source of local production of leptin.

PMID- 15572850
TI  - The effects of add-on zafirlukast treatment to budesonide on bronchial
      hyperresponsiveness and serum levels of eosinophilic cationic protein and total
      antioxidant capacity in asthmatic patients.
AB  - Mild persistent asthma is most effectively controlled with inhaled
      corticosteroids. Leukotriene receptor antagonists have complementary effects to
      corticosteroids on inflammation control. The additional effect of a leukotriene
      receptor antagonist, zafirlukast, was investigated in stable asthma patients
      under control with inhaled budesonide. We conducted a randomised, double-blind,
      placebo-controlled, single center trial to investigate the effects of add-on
      zafirlukast treatment to budesonide, on symptom score, pulmonary function,
      bronchial responsiveness, and serum levels of eosinophilic cationic protein (ECP)
      and antioxidant capacity in stable asthmatic patients under control with inhaled
      budesonide. The present study included 21 mild or moderate asthmatic patients (8
      males and 13 females), who were stable at least for 6 weeks with inhaled
      budesonide (400 microg/day). Serum total antioxidant capacity (TAC) and ECP
      levels were measured, and symptom scoring, spirometry, and bronchial provocation
      with methacholine were performed. Then, the patients were randomised to use
      either placebo or oral zafirlukast (40 mg/day) in addition to budesonide for 6
      weeks. At the 6th week, symptom scoring, spirometry, and bronchial provocation
      tests were repeated and serum TAC and ECP levels were measured again. After add
      on zafirlukast treatment to budesonide, forced expiratory volume in 1 second
      (FEV(1)), TAC and ECP values did not change significantly (p > 0.05) but
      bronchial hyperresponsiveness and symptom score decreased significantly (p =
      0.022) compared to baseline. Thus, in stable asthmatic patients, add-on
      zafirlukast treatment to budesonide improves symptoms and decreases bronchial
      hyperresponsiveness.

PMID- 15572851
TI  - Growth hormone cannot enhance the recovery of dexamethasone-induced osteopenia
      after withdrawal in young female wistar rats.
AB  - Dexamethasone (DEX) suppresses the secretion of and responsiveness to growth
      hormone (GH). Here we aimed to assess the therapeutic effects of GH on the DEX
      induced osteopenia. Female Wistar rats were treated for 2 weeks with DEX (200
      microg/day) or saline as a control. DEX significantly decreased body weight gain,
      bone mineral density (BMD), growth plate thickness, area ratio of trabecular
      bone, and serum osteocalcin levels. DEX also elongated the tibia primary
      spongiosa and caused many tiny lipid droplets in the tibia marrow. These results
      indicated that DEX induced osteopenia in rats. We then assessed the effects of GH
      on the recovery of osteopenia after withdrawal of DEX. DEX-treated rats were
      subsequently treated for 1 week with GH (0.1 or 0.3 U/day) or saline, while
      saline-pretreated rats were treated for 1 week with saline as a control. GH (0.1
      or 0.3 U/day)-treated rats showed a catch-up growth in various bone measurements
      by one week after DEX withdrawal, though most of them remained subnormal. GH
      treatment did not enhance the recovery of DEX-induced osteopenia. Therefore a
      short-term exposure to DEX significantly impaired the bone metabolism, which
      started to recover soon after withdrawal of DEX. Unfortunately, immediate
      administration of GH after withdrawal of DEX did not enhance the recovery
      process.

PMID- 15572852
TI  - The effect of surgical treatment of obstructive sleep apnea syndrome on the
      plasma TNF-alpha levels.
AB  - Obstructive sleep apnea syndrome (OSAS) is defined as intermittent complete or
      partial upper airway obstruction during sleep, causing mental and physical
      effects. Both the local and systemic inflammation observed in OSAS induce certain
      potent pro-inflammatory mediators, which may contribute to the development of
      cardiovascular consequences. The present study was designed to evaluate the
      plasma levels of TNF-alpha, which is one of the known pro-inflammatory cytokines,
      in patients with OSAS and to assess the effect of surgical treatment on the
      levels of TNF-alpha levels. Twenty seven patients diagnosed to have OSAS, 7 non
      apneic patients with chronic tonsillitis (non-OSAS patients), and 4 healthy
      subjects were enrolled in this study. Blood samples were collected one week
      preoperatively and postoperatively, and the plasma TNF-alpha levels were measured
      using high-sensitivity ELISA. The plasma TNF-alpha levels in patients with OSAS
      were significantly elevated in comparison to normal healthy subjects. In
      contrast, there was no difference between the patients with non-OSAS and healthy
      subjects. Moreover, the surgical treatment to enlarge the upper airway in
      patients with OSAS significantly decreased the levels of TNF-alpha levels.
      Surgical treatment of patients with OSAS reduces the plasma TNF-alpha levels,
      thereby ameliorating the systemic inflammation and preventing the development of
      cardiovascular consequences.

PMID- 15572853
TI  - Relationship between major depression and high serum cholesterol in Japanese men.
AB  - Although it has been argued that those with lower levels of serum cholesterol are
      likely to be depressive, the findings are inconsistent. The present study
      attempted to clarify the relationship between major depression and serum total
      cholesterol in a working population. Subjects were 987 Japanese men working at an
      institute, aged 20 to 64 years. In addition to blood examinations and physical
      measurements, clinical structured interviews of the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV) were used to detect major
      depression. The prevalence of major depression was higher in the
      hypercholesterolemics (serum total cholesterol levels > or = 5.69 mmol/liter)
      than in the normocholesterolemics (3.10-5.69 mmol/liter) (6.1% vs 1.8%, p <
      0.05). Notably, there was no case with major depression among the
      hypocholesterolemics (< 3.10 mmol/liter). Through a multiple regression analysis,
      serum total cholesterol levels were positively predicted by the following four
      variables: major depression, age, body mass index, and skipping breakfast (all p
      < 0.01). Concerning those diagnosed with major depression, serum total
      cholesterol levels remained higher in the following year (p < 0.05), comparing to
      those without such diagnosis. Therefore, depression is associated with higher
      serum cholesterol levels in a population of Japanese male workers. The
      irregularity of eating behavior may be one of the factors mediating high serum
      cholesterol levels and major depression.

PMID- 15572854
TI  - Increased mRNA expression of Th1-cytokine signaling molecules in patients with
      HTLV-I-associated myelopathy/tropical spastic paraparesis.
AB  - Expression of inflammatory cytokines derived from Th1 cell population is
      increased in patients with human T-lymphotropic virus type I (HTLV-I)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). It has been shown that
      cytokine signaling molecules, including transcription factors T-bet and GATA-3,
      interleukin-12 receptor beta 2 (IL-12R beta 2) and suppressors of cytokine
      signaling (SOCS), such as SOCS1, are important in differentiation of naive T
      cells into Th1 helper T cells. To assess the immunological status from the stand
      point of cytokine signaling in patients with HAM/TSP, we analyzed mRNA expression
      of these cytokine signaling molecules in peripheral blood mononuclear cells using
      quantitative RT-PCR. Twenty-eight HAM/TSP patients, nine HTLV-I-infected
      individuals without HAM/TSP and twenty-two HTLV-I-uninfected individuals were
      included in this study. Expression of T-bet, GATA-3, IL-12R beta 2 and SOCS1 was
      significantly increased in HAM/TSP patients in comparison with HTLV-I-uninfected
      individuals. In contrast, expression of SOCS3, a marker for Th2 cells, was
      significantly decreased in HTLV-I-infected individuals. These results indicate
      that HAM/TSP patients are associated with increased Th1 and decreased Th2
      cytokine signaling activities.

PMID- 15572855
TI  - Hypolipidemic drugs can change the composition of rat brain lipids.
AB  - Hypolipidemic drugs are potent serum cholesterol lowering agents used for
      prevention of coronary heart disease. In addition to their cholesterol lowering
      effect, these drugs exhibit both pleiotropic beneficial and various neurological
      side effects. Therefore, we analysed effect of the hypolipidemic drugs,
      fenofibrate and statins, on membrane lipid composition in the rat brain tissue.
      Male Wistar rats were given 0.1 mg of fenofibrate, lovastatin, pravastatin,
      fluvastatin or placebo (control) once daily for six weeks. In rats treated with
      lovastatin or pravastatin, decreased cholesterol and increased ceramide
      monohexoside contents in the brain tissue were observed in comparison with
      control. Treatment with fluvastatin or lovastatin resulted in increased
      sphingomyelin and decreased diphosphatidylglycerol contents. The most important
      changes in the fatty acid profile were observed in ceramide monohexosides;
      treatment with fluvastatin decreased the content of saturated and increased the
      content of polyunsaturated fatty acids. Fenofibrate treatment led to decreased
      content of saturated fatty acids in phosphatidylethanolamines. In conclusion,
      statin treatment resulted in the decreased content of cholesterol and
      diphosphatidylglycerol associated with the increased content of sphingolipids in
      the rat brain tissue. As cholesterol and sphingolipids are important components
      of brain membranes, the observed alterations in the composition brain lipids
      might be involved in genesis of neurological and mental symptoms following statin
      therapy.

PMID- 15572856
TI  - Retrospective analysis of concurrent chemoradiation with the combination of
      bleomycin, ifosfamide and cisplatin (BIP) for uterine cervical cancer.
AB  - Combination chemotherapy consisting of bleomycin, ifosfamide, and ciplatin (BIP)
      is recognized as one of the most effective chemotherapies for uterine cervical
      cancer. However, there have been no reports that evaluate concurrent use of
      radiation with BIP. The objective of this study was to evaluate the toxicity and
      response of the combination of BIP concurrent with radiation in patients with
      squamous cell carcinoma of the uterine cervix. Eligibility criteria included
      patients who underwent radical hysterectomy (Type III hysterectomy) as a primary
      treatment and revealed lymph node metastases or deep myometrial invasion (stage
      IB and IIA) and patients who were previously untreated (stage IIB-IV). All of the
      patients had biopsy-proven squamous cell carcinoma of the uterine cervix. The
      patients received three courses of BIP chemoradiation, and the response and
      toxicity were evaluated. From January 2000 to December 2003, 30 patients met
      study eligibility criteria. All but three patients completed 3 courses of planned
      chemotherapy. The frequency of severe (grade 3 and 4) toxicity was as follows:
      anemia, 46.7%; neutrocytopenia, 73.3%; thrombocytopenia, 16.7%; and nausea and
      vomiting, 23.3%. Among 30 patients, 22 cases were evaluated for response.
      Complete response was achieved in 16 (72.7%) of patients, with a response rate of
      90.9%. In conclusion, BIP chemoradiation seems to be superior to previously
      reported chemoradiation regimens, and has a potential as an optimal combination
      chemotherapy concurrent with radiation.

PMID- 15572857
TI  - Desmoplastic medulloblastoma in a 48-year-old male.
AB  - Medulloblastoma is a malignant invasive embryonal tumor of the cerebellum with
      preferential manifestation in children. The peak of occurrence is seven years of
      age. Seventy percent of medulloblastomas occur in individuals younger than 16. In
      adulthood, 80% of medulloblastomas arise in the 21-40 years age group. A 48-year
      old male patient was admitted to the hospital with complains of headache, ataxia,
      morning vomiting and difficulty in speech was operated with the diagnosis of
      presence of mass of 4 x 7 cm size retaining a diffuse homogenous contrast in the
      posterior fossa. The diagnosis of desmoplastic medulloblastoma was given after
      histopathological examination. Immunohistochemical examination revealed that
      neoplastic cells showed staining with neuron-specific enolase and synaptophysin
      but not with glial fibrillary acidic protein. This lesion showed nodular,
      reticulin free-zones (pale islands) surrounded by densely packed, highly
      proliferative cells. The pale regions within the tumor did not contain reticulin
      fibers. Desmoplastic medulloblastoma is encountered especially in adulthood. This
      type of tumor rarely occurs beyond the fifth decade of life. We present a case of
      desmoplastic medulloblastoma in a 48-year-old male.

PMID- 15572858
TI  - Acrosome reaction in spermatozoa from the amphioxus Branchiostoma belcheri
      (Cephalochordata, Chordata).
AB  - The formation of an acrosomal process at acrosomal exocytosis in spermatozoa of
      the amphioxus was described in the present report for the first time. A non
      reacted acrosome was located in front of the nucleus, where a cup-shaped
      acrosomal vesicle covered a conical accumulation of subacrosomal material. When
      naturally spawned spermatozoa were treated with a calcium ionophore, ionomycin,
      the acrosomal vesicle opened at the apex and an acrosomal process was projected.
      The process exhibited a filamentous structure. The reaction followed the mode
      typically seen in marine invertebrates. These observations suggest that the
      features and function of the acrosome of amphioxus, whose position is on the
      border between invertebrates and vertebrates, reflect their ecological adaptation
      and phylogenic position.

PMID- 15572859
TI  - A drastic reduction in the basal level of heat-shock protein 90 in the brain of
      goldfish (Carassius auratus) after administration of geldanamycin.
AB  - Geldanamycin (GA), a specific inhibitor of the chaperoning function of heat-shock
      protein 90 (Hsp90), has been shown to mimic heat shock (HS) in inducing
      expression of Hsp90, Hsp72 and other Hsps in unstressed mammalian cells. In the
      present study, intra-cerebral treatment of goldfish with GA (at a dose of 0.1
      microg/g-body weight) diminished basal Hsp90 level to a 30-40% level in the
      brain, without affecting the basal Hsp72 level, as assayed 28-48 h after
      treatment. Whole-body exposure to HS significantly increased Hsp90 level in GA
      untreated fish but not in GA-treated fish, while it significantly increased Hsp72
      level in both GA-untreated and -treated fish. In both GA-untreated and -treated
      fish, plasma cortisol (PC) levels increased considerably 4 h after HS and then
      decreased in a time-dependent manner to the control levels 24 h after HS, showing
      no evidence of a GA effect on the time course of PC level. These results suggest
      that in the brain of goldfish, Hsp90 may not be involved as a key factor either
      in regulating Hsp72 expression both before and after HS or in the feedback
      regulation of HS-increased PC level, and support the idea that GA can be used in
      fish brain as a tool in elucidating the role of Hsp90 in complicated, Hsp
      mediated biological processes.

PMID- 15572860
TI  - Membrane potential responses of paramecium caudatum to external Na+.
AB  - The membrane potential responses of Paramecium caudatum to Na+ ions were examined
      to understand the mechanisms underlying the sensation of external inorganic ions
      in the ciliate by comparing the responses of the wild type and the behavioral
      mutant. Wild-type cells exhibited initial continuous backward swimming followed
      by repeated transient backward swimming in the Na+-containing test solution. A
      wild-type cell impaled by a microelectrode produced initial action potentials and
      a sustained depolarization to an application of the test solution. The prolonged
      depolarization, the depolarizing afterpotential, took place subsequently after
      stimulation. The ciliary reversal of the cell was closely associated with the
      depolarizing responses. When the application of the test solution was prolonged,
      the wild-type cell produced sustained depolarization overlapped by repeated
      transient depolarization. A behavioral mutant defective in the Ca2+ channel, CNR
      (caudatum non reversal), produced a sustained depolarization but no action
      potential or depolarizing afterpotential. The mutant cell responded to prolonged
      stimulation with sustained depolarization overlapped by transient depolarization,
      although it did not show backward swimming. The results suggest that Paramecium
      shows at least two kinds of membrane potential responses to Na+ ions: a
      depolarizing afterpotential mediating initial backward swimming and repeated
      transient depolarization responsible for the repeated transient backward
      swimming.

PMID- 15572861
TI  - Progression of flagellar stages during artificially delayed motility initiation
      in sea urchin sperm.
AB  - Transition from immotile to motile flagella may involve a series of states, in
      which some of regulatory mechanisms underlying normal flagellar movement are
      working with others being still suppressed. To address ourselves to the study of
      starting transients of flagella, we analyzed flagellar movement of sea urchin
      sperm whose motility initiation had been retarded in an experimental solution, so
      that we could capture the instance at which individual spermatozoa began their
      flagellar beating. Initially straight and immotile flagella began to shiver at
      low amplitude, then propagated exclusively the principal bend (P bend), and
      finally started stable flagellar beating. The site of generation of the P bend in
      the P-bend propagating stage varied in position in the basal region up to 10
      microm from the base, indicating that the ability of autonomous bend generation
      is not exclusively possessed by the very basal region but can be unmasked
      throughout a wider region when the reverse bend (R bend) is suppressed. The rate
      of change in the shear angle, the curvature of the R bend and the frequency and
      regularity of beating substantially increased upon transition from P-bend
      propagating to full-beating, while the propagation velocity of bends remained
      unchanged. These findings indicate that artificially delayed motility initiation
      may accompany sequential modification of the motile system and that mechanisms
      underlying flagellar motility can be analyzed separately under experimentally
      retarded conditions.

PMID- 15572862
TI  - Isolation and cDNA cloning of ovarian cortical rod protein in kuruma prawn
      Marsupenaeus japonicus (Crustacea: Decapoda: Penaeidae).
AB  - Two cortical rod proteins having molecular weights of 28.6 kDa and 30.5 kDa were
      isolated from the mature ovary of Marsupenaeus japonicus using gel filtration and
      reversed-phase HPLC. Analysis of the N-terminal amino acid sequence of the 28.6
      kDa molecule revealed that amino acid residues 1-21 corresponded to residues 9-29
      of the 30.5 kDa molecule. Examination of homology using BLAST showed that 21
      amino acids out of 29 residues of the 28.6 kDa molecule, and 14 out of 29
      residues of the 30.5 kDa molecule were identical to that of the ovarian cortical
      rod proteins of Penaeus semisulcatus. Positive immunohistochemical reaction to
      antiserum raised against the 28.6 kDa protein was observed on cortical rods
      forming around the periphery of oocytes at the maturation stages. Western
      blotting analysis revealed that both the 28.6 kDa and 30.5 kDa molecules stained
      with the anti-28.6 kDa antiserum. Furthermore, the 28.6 kDa and 30.5 kDa proteins
      were both glycosylated, as evidenced by positive carbohydrate staining using
      Concanavalin A and production of positive PAS reaction. These results indicate
      that the cortical rods are comprised of the 28.6 kDa and 30.5 kDa molecules. We
      subsequently cloned two full-length cDNAs based on the N-terminal sequences of
      the 28.6 kDa and 30.5 kDa molecules. The open reading frame of 28.6 kDa and 30.5
      kDa encoded 276 amino acid residues. Comparison analysis of the two cDNAs
      revealed that the location of the processing site and sequence of signal peptides
      differed, indicating that the two cDNAs are products of two separate genes and
      encode the 28.6 kDa molecule and 30.5 kDa molecule, respectively. Both proteins
      possessed one potential N-linked glycosylation site. It is considered that both
      molecules are components of the cortical rods, forming a jelly layer after
      fertilization.

PMID- 15572863
TI  - Effect of a glycine residue insertion into crustacean hyperglycemic hormone on
      hormonal activity.
AB  - Crustacean hyperglycemic hormone (CHH) and molt-inhibiting hormone (MIH) have
      similar amino acid sequences and therefore comprise a peptide family referred to
      as the CHH family. All MIHs unexceptionally have an additional glycine residue at
      position 12, which is lacking in all CHHs. In order to understand the relevance
      of the absence of the glycine residue for hyperglycemic activity, a mutant CHH
      having a glycine residue insertion was prepared, and its hyperglycemic activity
      was assessed. This mutant CHH had the same disulfide bond arrangement as the
      recombinant CHH produced in Escherichia coli cells, and exhibited a similar
      circular dichroism spectrum to the recombinant CHH, indicating that the two CHHs
      possessed similar conformations. The mutant CHH showed a hyperglycemic effect
      weaker than the recombinant CHH by about one order of magnitude. These results
      suggest that the insertion of a glycine residue is one of the indices for
      structural and functional divergence of the CHH family peptides.

PMID- 15572864
TI  - Secretion patterns of growth hormone in growing captive mithuns (Bos frontalis).
AB  - A study was conducted in May 2003 to characterize plasma growth hormone (GH)
      pattern in growing mithuns (Bos frontalis), a rare semi-wild ruminant. Six mithun
      calves averaging 235 day of age and 124 kg were maintained in semi-intensive
      system and group-fed once daily. Animals gained at a mean rate of 0.54 kg/day,
      with individuals ranging from 0.34 to 0.66 kg/day. Blood samples collected at 15
      minute intervals starting from 0600h for nine-hour period were assayed for plasma
      GH. Growth hormone patterns consisted of frequent pulses of varying amplitude.
      Growth hormone pulses occurred at an average frequency of 0.69/h, the rate did
      not differ markedly among mithuns nor hour of day. The magnitude of GH secretory
      pulses varied significantly among mithuns. Growth hormone peaks averaged 95.0 and
      45.2 ng/ml in mithuns having the highest and lowest GH peaks, respectively. Peak
      and mean GH levels were associated positively (r=0.98, P<0.001) and both were
      associated negatively (r=-0.97 and -0.98, respectively; P<0.01) with rates of
      gain. Results from the study show that 1) GH peaks occur at frequent intervals
      throughout the sampling period and 2) alteration in GH levels and patterns are
      elicited more by pulse amplitude than frequency modulation.

PMID- 15572865
TI  - A new deep-water lancelet (Cephalochordata) from off Cape Nomamisaki, SW Japan,
      with a proposal of the revised system recovering the genus Asymmetron.
AB  - Asymmetron inferum n. sp. is established for the holotype collected during the
      Hyper-Dolphin/Natsushima cruise in 2003 of the Japan Marine Science & Technology
      Center (JAMSTEC) off Cape Nomamisaki, southwestern end of Kagoshima Prefecture,
      at a depth of 229 m. A. inferum is very similar to its congener, A. lucayanum
      Andrews, 1893 (formerly called Epigonichthys lucayanus) but easily
      distinguishable from it by the larger number of total myotomes (83 in the former
      vs. 55-72 in the latter). The genus Asymmetron has been treated as a junior
      synonym of Epigonichthys, but is recovered as a valid genus distinct
      morphologically from another valid genus Epigonichthys (sensu stricto).

PMID- 15572866
TI  - [Medicinal and herbal plants: a graded and global offering of drugs].

PMID- 15572867
TI  - [Influence of homeopathically processed coenzyme q10 on proliferation and
      redifferentiation of endothelial cells].
AB  - BACKGROUND: Coenzyme Q10 (Co Q10) is vital for regulating cell metabolism and
      cell proliferation. The controlled proliferation of cells is prerequisite for the
      regeneration of tissues. AIM: The aim of this study was to clarify whether
      homeopathically processed Co Q10 has an influence on the proliferation of freshly
      seeded endothelial cells, on the division rate of differentiated confluent
      endothelial cells, and on the redifferentiation of differentiated endothelial
      cells in vitro. METHODS: By the determination of cell numbers, the influence of
      Co Q10 on the proliferation of undifferentiated endothelial cells from the human
      umbilical vein was examined. For this assay different potencies of Co Q10 and
      freshly seeded endothelial cells were used. Prior to the proliferation assay the
      in vitro cytotoxic concentrations of Co Q10 were determined. The influence of Co
      Q10 on the division rate of differentiated confluent endothelial cells was
      determined by measuring the intake of the base analogue bromodeoxyuridine (BrdU).
      For the testing of differentiation, the expression of the von Willebrand factor
      (vWF) - the marker protein typical for endothelial cells - was observed while Co
      Q10 was present. A flow cytometric assay was used for the analyses. RESULTS:
      While only the D5 potency showed toxic effects, the other tested potencies of Co
      Q10 did not show any cytotoxicity. The potencies D7-D10 of Co Q10, especially the
      D8 potency, caused an increase in the proliferation of growing endothelial cells.
      By contrast, Co Q10 (D8) had no influence on the rate of incorporation of BrdU
      into confluent, contact-inhibited, and differentiated endothelial cells. In the
      case of confluent dedifferentiated cells incubated with Co Q10 (D8), no increase
      in the expression of the vWF was observed, either. CONCLUSIONS: Homeopathically
      processed Co Q10 (D8) has a stimulating influence on the proliferation of growing
      cells in vitro. This confirms its function in the regulation of cell metabolism
      and cell proliferation. The stimulating influence, however, does not extend to
      the redifferentiation process. Co Q10 has no effect on the low division rate of
      subconfluent and of confluent, contact-inhibited, differentiated endothelial
      cells. Furthermore the expression of endothelial cell-specific differentiation
      antigens on dedifferentiated endothelial cells is not influenced by Co Q10.

PMID- 15572868
TI  - A double-blind, randomized, homeopathic pathogenetic trial with healthy persons:
      comparing two high potencies.
AB  - BACKGROUND AND OBJECTIVE: According to homeopathic theory, symptoms provoked by
      the homeopathic remedy in a pathogenetic trial (PT) make up the remedy picture
      serving as the basis for the homeopathic treatment. Little is known whether the
      symptoms produced by the remedy differ from symptoms produced by placebo. This is
      because both homeopathic remedy and placebo also produce so-called unspecific
      effects due to psychological reasons. We therefore explore the distinctiveness of
      homeopathic symptoms and placebo symptoms. DESIGN: A three-armed, randomized PT
      pilot study. SETTING: A blinded materia medica expert identifies symptoms with
      regard to their number and specificity. PARTICIPANTS: 21 healthy homeopathic
      practitioners note symptoms produced after remedy intake. INTERVENTIONS: Patients
      are randomly assigned to receive either (1) Calendula officinalis, (2) Ferrum
      muriaticum, or (3) placebo. After a seven-day baseline symptoms recording period,
      proving substances are taken until symptoms occur. In daily supervision phone
      calls, symptoms are verified by the supervisor. MAIN OUTCOME MEASURE: Total
      number of symptoms produced and number of specific symptoms produced. OUTLOOK:
      The results showed that both remedies 'produced' significantly more symptoms than
      placebo. With regard to the specificity, the Calendula officinalis group
      displayed more remedy-specific symptoms than placebo. However, in the Ferrum
      muriaticum group more Calendula symptoms than placebo were also recorded.

PMID- 15572869
TI  - Growth stimulation of dwarf peas (Pisum sativum L.) through homeopathic potencies
      of plant growth substances.
AB  - BACKGROUND: Efficacy of higher homeopathic potencies is controversial.
      Universally accepted specific detection assays for homeopathic dilutions do not
      exist. Basic research has to develop a spectrum of standardized tools to
      investigate the mode of action and nature of homeopathic potencies. OBJECTIVE:
      Can the shoot growth reaction of dwarf peas (gibberellin- deficient mutants) be
      regarded as evidence of treatment with homeopathic potencies of plant growth
      substances? MATERIALS AND METHODS: Pea seed (Pisum sativum L. cv. Fruher Zwerg)
      is immersed for 24 hours in homeopathic potency or control solutions for soaking.
      Plants germinate and grow in a standard cultivation substrate under controlled
      environmental conditions. Shoot length is measured 14 days after planting.
      RESULTS: A screening of homeopathic potencies (12x-30x) of four different plant
      growth substances revealed biological activity of certain potency levels of
      gibberellin and kinetin (p < 0.05). Growth stimulation through gibberellin 17x (5
      x 10(-18 M)) was assessed in six independent replications; results confirmed
      those of the screening (p < 0.05). The effect of gibberellin 17x seemed to weaken
      during the course of the experiments. CONCLUSION: The results back the hypothesis
      that homeopathic potencies of plant growth substances affect pea shoot growth.
      Dwarf peas might thus be an interesting system model for studying the action of
      homeopathic potencies. Further work is required to identify all boundary
      conditions modulating the reactivity of this system.

PMID- 15572870
TI  - [Development of 'Ordnungstherapie' by Bircher-Benner in naturopathy of the 20th
      century].
AB  - BACKGROUND: The German term 'Ordnungstherapie' is one of the five therapeutics
      which defines naturopathy in German-speaking countries. OBJECTIVE: Who formed the
      term Ordnungstherapie in naturopathy and what does it mean? MATERIAL AND METHODS:
      Heuristics and criticism of literature of the 20th century as well as database
      research. RESULTS: Nowadays in German-language medical books Ordnungstherpie
      belongs to the five therapeutics which define European naturopathy. Yet, the
      interpretation ranges from health education to body-orientated forms of
      psychotherapy. The term Ordnungstherapie is often related with the German priest
      and hydropath Sebastian Kneipp, however, term and definition have been founded by
      the Swiss physician Maximillian Bircher-Benner. In 1937 he defined
      Ordnungstherapie as a complex concept of natural healing. It is based upon the
      rather nosological idea that health is order/harmony in the human body
      (physically, psychologically), the environment and the daily course. Illness
      occurs if disorder appears in one of these fields. The therapeutic setting of
      Ordnungstherapy is defined by 9 rules of conduct to maintain order, which include
      nutrition, the skin as an organ (exposure to light, air, water), breathing,
      movement, rhythm of life, and psyche. For all these aspects Bircher-Benner
      himself uses the terms somatotherapy (dietotherapy, sun and light therapy,
      hydrotherapy, exercise therapy, breathing technique, order of the rhythm of live)
      and psychotherapy. He chose these complementary methods subjectively after
      learning them from 1897 onwards in an eclectic manner and after gaining
      therapeutic empiricism. Nevertheless his ideas of the Ordnungstherapie correlate
      with the socio-political context of the 1940ies. CONCLUSIONS: The term
      Ordnungstherapie was introduced by Bircher-Benner as an umbrella term in 1937 to
      describe a complex concept of naturopathic therapies. It comprises, with certain
      limitations for phytotherapy, the therapies which nowadays define European
      naturopathy. Yet, in European naturopathy today Ordnungstherapie is mostly
      considered as one out of 5 constituents of naturopathy (dietotherapy,
      hydrotherapy, exercise therapy, phytotherapy, Ordnungstherapie). The
      classification of Ordnungstherapie as one of the 5 pillars of the Kneipp therapy
      was only done by Kneipp physicians in the middle of the 20th century and needs to
      be thought over.

PMID- 15572871
TI  - Hydrolysis of casein accelerates gastrointestinal transit via reduction of opioid
      receptor agonists released from casein in rats.
AB  - BACKGROUND: Protein hydrolysate accelerates gastrointestinal transit (GIT) and
      feeding advancement in preterm infants compared to native protein. In rat pups,
      opioid receptor agonists released from casein during digestion such as beta
      casomorphins slow down GIT. We hypothesized that hydrolysis of casein reduces the
      opioid activity released during digestion thereby accelerating GIT compared to
      native casein. OBJECTIVE: The aim of the present study was to investigate whether
      casein hydrolysate accelerates GIT compared to native casein and whether
      pretreatment with naloxone, an opioid receptor blocker, abolishes this difference
      in rat pups. METHODS: In a randomized controlled trial following a 2 x 2
      factorial design, 216 female Wistar rat pups were fed with pellets based on
      hydrolyzed or native casein. After pretreatment with naloxone or normal saline,
      carmine red was administered by oro-gastric gavage as a tracer for GIT velocity
      measurement. Four hours later the animals were sacrificed, their intestine was
      removed and the length of the colon from the cecocolonic junction to the anus was
      measured. GIT was recorded as percentage of the total colonic length (percentage
      of colonic transit) passed by carmine red. Data were given as mean +/- SD.
      RESULTS: GIT was significantly higher with hydrolyzed casein compared to native
      casein formula (77.4 +/- 17 and 51.2 +/- 20%), but there was no difference after
      naloxone pretreatment (77.1 +/- 16 and 76.5 +/- 17%). DISCUSSION: The present
      data suggest that hydrolysis of casein accelerates GIT via reduction of opioid
      activity released during digestion. Further studies are required to investigate
      to which extent these rat pub data apply to preterm infants.

PMID- 15572872
TI  - Correlation of entorhinal amyloid with memory in Alzheimer's and vascular but not
      Lewy body dementia.
AB  - OBJECTIVE: To examine the relationship of the anatomic distribution of amyloid
      deposition to focal and global cognitive dysfunction in different subtypes of
      dementia. METHODS: We quantified AB40 and AB42 in the temporal lobe and
      entorhinal cortex and examined their relationship to cognitive functions in
      Alzheimer's disease (AD), vascular dementia (VaD) and dementia with Lewy bodies
      (DLB). RESULTS: We found a correlation between memory impairment, but not global
      cognitive impairment, and amyloid load in these areas in AD and VaD but not in
      DLB. This relationship was stronger for AB42 and in the entorhinal cortex.
      CONCLUSION: The anatomic location of amyloid deposition is an important factor
      specific factor in memory impairment in AD and VaD.

PMID- 15572873
TI  - Pathological validation of a CT-based scale for subcortical vascular disease. The
      OPTIMA Study.
AB  - The validity of a computed tomography (CT)-based rating scale that separately
      rates leukoaraiosis, patchy lesions, and lacunes was tested using
      neuropathological findings collected on 87 subjects enrolled in the Oxford
      Project to Investigate Memory and Ageing. The CT-based score (range 0-64) was
      associated with both small vessel disease (p = 0.015) and microinfarcts (p =
      0.002) on pathology. A sum score of subcortical cerebrovascular disease (CVD) on
      pathology was computed, 0 indicating absent/mild small vessel CVD and no
      microinfarcts, 1 moderate small vessel CVD or microinfarcts, and 2 and higher
      both conditions or severe small vessel CVD. Subjects with a sum score of 0 were
      decreasing with increasing severity of CT-based score (64, 46, and 25% in those
      with CT-based scores of 0, 1-38, and 39 and higher), while those with a sum score
      of 2 and higher were increasing (0, 14, and 44%; p = 0.002). A standardized
      assessment of subcortical CVD on CT films can be compounded into a unique score
      that is in good agreement with neuropathology. This supports the validity of the
      CT-based visual rating scale as a valid tool to detect subcortical vascular
      changes in elderly persons.

PMID- 15572874
TI  - Prevalence of mild cognitive impairment in 60- to 64-year-old community-dwelling
      individuals: The Personality and Total Health through Life 60+ Study.
AB  - This epidemiological study aimed at determining the prevalence of mild cognitive
      impairment (MCI) in 60- to 64-year-old individuals using different diagnostic
      criteria. Community dwelling individuals (n = 2,551) in the age range of 60-64
      years were recruited randomly through the electoral roll. They were screened
      using the MMSE and a short cognitive battery, and those who screened positive
      underwent detailed medical and cognitive assessments. Extant MCI-related
      diagnoses were established by consensus. Predictive regression models on the sub
      sample were used to determine population prevalence for the diagnoses. Of the 224
      subjects who screened positive for MCI, 112 underwent a detailed assessment and
      74% met the criteria for at least one recognised diagnosis of mild cognitive
      deficit (MCI and related diagnoses). By predictive regression modelling, the
      prevalence of any MCI diagnosis was 13.7% (95% CI 9.1-30.2) in the population of
      60- to 64-year-olds. The estimated prevalence rates for specific diagnoses were:
      MCI 3.7%, ageing-associated cognitive decline 3.1%, Clinical Dementia Rating
      score (0.5) 2.8%, age-associated memory impairment 1%, other cognitive disorders
      0.9%, and mild neurocognitive disorder 0.6%. Agreement on 'caseness' between
      various proposed diagnoses was at best fair and generally poor. Memory and other
      cognitive problems not meeting the threshold for dementia are relatively common
      in 60- to 64-year-old individuals living in the community. The prevalence rate
      varies up to six-fold according to the diagnostic criteria applied, with limited
      overlap between diagnoses. There is an urgent need for standardization of the
      criteria.

PMID- 15572875
TI  - Semantic memory impairment in the earliest phases of Alzheimer's disease.
AB  - The presence and the nature of semantic memory dysfunction in Alzheimer's disease
      (AD) have been widely debated. This study aimed to determine the frequency of
      impaired semantic test performances in mild AD and to study whether incipient
      semantic impairments could be identified in predementia AD. Five short
      neuropsychological tests sensitive to semantic memory and easily applicable in
      routine practice were administered to 102 patients with mild AD (Mini-Mental
      State Examination score above 19), 22 predementia AD patients and 58 healthy
      subjects. 'Category fluency' and 'naming of famous faces' were the most
      frequently impaired tests in both patient groups. The study demonstrated that
      impairments on semantically related tests are common in mild AD and may exist
      prior to the clinical diagnosis. The results imply that assessment of semantic
      memory is relevant in the evaluation of patients with suspected AD.

PMID- 15572876
TI  - Responsiveness of the quality of life in late-stage dementia scale to
      psychotropic drug treatment in late-stage dementia.
AB  - BACKGROUND: We report on the responsiveness of a previously validated quality-of
      life scale, the Quality of Life in Late-Stage Dementia scale (QUALID), as an
      outcome measure in a clinical trial of two psychotropic medications. METHODS:
      Secondary analyses were conducted comparing outcome measures used in a randomized
      double-blind trial of two antipsychotics (olanzapine and risperidone) for the
      treatment of dementia-related behavioral symptoms. The QUALID was completed for
      31 of the patients in addition to several measures of behavior-related dementia
      symptoms including the Neuropsychiatric Inventory, the Withdrawn Behavior
      subscale of the Multidimensional Observation Scale for Elderly Subjects, the Mini
      Mental State Examination, and the Clinical Global Impression. Measures of safety
      and adverse effects included the Simpson-Angus Scale and records of specific
      adverse events. RESULTS: A significant positive relationship was found between
      QUALID score and improvement in behavioral symptoms, and a negative association
      was found with adverse medication effects. CONCLUSIONS: The QUALID was sensitive
      to both the treatment effects and the adverse effects of medication in this
      sample of patients.

PMID- 15572877
TI  - Executive function impairment in community elderly subjects with questionable
      dementia.
AB  - BACKGROUND: The neurocognitive profile of community-dwelling Chinese subjects
      with 'questionable' dementia was studied. METHODS: One hundred and fifty-four
      ambulatory Chinese subjects were recruited from local social centers for the
      elderly. Each subject was examined using the Clinical Dementia Rating (CDR), the
      Cantonese version of the Mini-Mental State Examination (CMMSE), the Chinese
      version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS
      Cog), the Category Verbal Fluency Test (CVFT), digit and visual span tests, and
      the Cambridge Neurological Inventory. The neurocognitive profile of nondemented
      subjects (CDR 0) was compared with that of subjects with 'questionable' dementia
      (CDR 0.5). RESULTS: Subjects with 'questionable' dementia were older, and had
      lower educational levels and global cognitive assessment scores than the controls
      (CMMSE and ADAS-Cog; t tests, p < 0.001). In addition, they also had
      significantly lower scores in delayed recall, reverse span, verbal fluency tests
      and worse performance in complex motor tasks related to executive function (Mann
      Whitney tests, p < 0.001). Logistic regression analysis revealed that ADAS-Cog,
      CVFT, and reverse visual span were significant predictors for the CDR of
      'questionable' dementia. CONCLUSION: Aside from memory impairment, executive
      function deficits were also present in subjects with 'questionable' dementia. To
      identify groups cognitively at risk for dementia, concomitant assessments of
      memory and executive function are suggested.

PMID- 15572878
TI  - The use of semen parameters to identify the subfertile male in the general
      population.
AB  - AIMS: To present a structured review of the literature published on semen
      parameters and in vivo fertility potential and to establish
      fertility/subfertility thresholds for sperm morphology using Tygerberg strict
      criteria, sperm concentration, and sperm motility. METHOD: The published
      literature comparing fertile and subfertile populations between 1983 and 2002 was
      reviewed. RESULTS: A total of 265 articles were identified by the sourcing
      methodology, but only four articles provided data that could be tabulated and
      analyzed. Using receiver-operating characteristics curves, morphology proved to
      be the best predictor of subfertility in 2 of the 4 articles, with concentration
      and motility also showing good predictive power. The thresholds calculated ranged
      between 4 and 10% for morphology, between 13.5 x 10(6)/ml and 34 x 10(6)/ml for
      concentration, and between 32 and 52% for motility. A second set of much lower
      thresholds was calculated in three of the articles using either a 15 or 50%
      prevalence of subfertility in the population or the tenth percentile of the
      fertile population. The adjusted thresholds were between 3 and 5% for morphology,
      between 9 x 10(6)/ml and 20 x 10(6)/ml for concentration, and between 20 and 30%
      for motility. CONCLUSIONS: Because these lower thresholds have a much higher
      positive predictive value, we suggest that thresholds of <5% normal sperm
      morphology, a concentration <15 x 10(6)/ml, and a motility <30% should be used to
      identify the subfertile male. The lower threshold for morphology also fits in
      vitro fertilization and intrauterine insemination data calculated previously.
      Using the parameters in combination increases the clinical value of semen
      analysis.

PMID- 15572879
TI  - Interactions between nitric oxide and arachidonic acid in lung epithelial cells:
      possible roles for peroxynitrite and superoxide.
AB  - This study investigated interactions between nitric oxide synthesis and
      phospholipase A2 (PLA2) activation in lung epithelial cells. Nitrite formation,
      inducible nitric oxide synthase expression, and [3H]arachidonic acid (AA) release
      were determined following treatment with: (1) the nitric oxide synthase
      inhibitors N(G)-nitro-L-arginine methyl esther (L-NAME) and aminoguanidine; (2)
      arachidonyl trifluoromethyl ketone (AACOCF3), a specific cytosolic PLA2
      inhibitor; (3) S-morpholinosydnonimine (SIN-1), a nitric oxide donor which
      provokes peroxynitrite formation; (4) trolox, a free radical scavenger, and (5)
      the AA release agonists calcium ionophore, phorbol 12-myristate 13-acetate, and
      sodium vanadate. The results demonstrated that (1) L-NAME and aminoguanidine
      inhibited agonist-induced AA release by 40 and 65%, respectively; (2) AACOCF3
      inhibited nitrite formation and inducible nitric oxide synthase expression in a
      dose-dependent manner; (3) SIN-1, together with AA release agonists,
      significantly increased the AA output, and (4) trolox counteracted the SIN-1
      effects. Our results demonstrate cross talk between nitric oxide synthase and
      PLA(2) pathways, with a possible intermediary role for peroxynitrite and
      superoxide.

PMID- 15572880
TI  - The role of pediatric gastroenterology and nutrition in developing countries.

PMID- 15572881
TI  - Childhood constipation: is there new light in the tunnel?

PMID- 15572882
TI  - Prebiotic oligosaccharides in dietetic products for infants: a commentary by the
      ESPGHAN Committee on Nutrition.
AB  - This article by the ESPGHAN Committee on Nutrition summarizes available
      information on the effects of adding prebiotic oligosaccharides to infant and
      follow-on formulae. Currently there are only limited studies evaluating prebiotic
      substances in dietetic products for infants. Although administration of prebiotic
      oligosaccharides has the potential to increase the total number of bifidobacteria
      in feces and may also soften stools, there is no published evidence of clinical
      benefits of adding prebiotic oligosaccharides to dietetic products for infants.
      Data on oligosaccharide mixtures in infant formulae do not demonstrate adverse
      effects, but further evaluation is recommended. Combinations and dosages in
      addition to those so far studied need to be fully evaluated with respect to both
      safety and efficacy before their use in commercial infant food products. Well
      designed and carefully conducted randomized controlled trials with relevant
      inclusion/exclusion criteria, adequate sample sizes and validated clinical
      outcome measures are needed both in preterm and term infants. Future trials
      should define optimal quantity and types of oligosaccharides with prebiotic
      function, optimal dosages and duration of intake, short and long term benefits
      and safety. At the present time, therefore, the Committee takes the view that no
      general recommendation on the use of oligosaccharide supplementation in infancy
      as a prophylactic or therapeutic measure can be made.

PMID- 15572883
TI  - Thirty years of the ESPGAN/ESPGHAN Committee on Nutrition.
AB  - The creation of the Committee on Nutrition of ESPGAN (later ESPGHAN) in 1974 was
      stimulated by the need to define generally acceptable standards for infant
      feeding and for dietetic products for infants. Since the late 1970s the Committee
      has published a series of widely respected authoritative comments that have
      provided guidance for pediatricians, regulatory bodies and manufacturers of food
      products in Europe and other parts of the world. The Committee and its members
      have also contributed to the development of standards by the Codex Alimentarius
      Committee of the World Health Organization and of the Food and Agriculture
      Organization of the United Nations, and of standards in the European Union. Among
      the further aims of the Committee aims is the stimulation and support of young
      researchers entering the field of nutrition and metabolism, as well as the
      lobbying for public and private funding that supports pediatric nutrition
      research. The strong tradition of 30 successful years with the achievements made,
      and the appreciation of the vision and determination of the pioneers who had
      built the Committee, provide a major stimulus to strive for continued excellence
      in achieving the Committee's mission.

PMID- 15572884
TI  - Case definition of intussusception: use and misuse.

PMID- 15572885
TI  - Diagnostic tests for childhood Helicobacter pylori infection: invasive,
      noninvasive or both?

PMID- 15572886
TI  - Kill the messenger of bad news?

PMID- 15572887
TI  - Colostrum protein concentrate enhances intestinal adaptation after massive small
      bowel resection in juvenile pigs.
AB  - OBJECTIVES: Short bowel syndrome (SBS) usually results from the surgical removal
      of a large segment of small intestine. Patient outcome depends on the extent of
      intestinal resection and adaptation of the remaining intestine. We evaluated the
      impact of colostrum protein concentrate (CPC) on intestinal adaptation after
      massive small bowel resection in a porcine model of infant SBS. METHODS: Four
      week-old piglets underwent an approximate 75% small bowel resection (R, n = 23)
      or a control transection operation (C, n = 14). Postoperatively, animals from
      both groups received either pig chow (R = 6, C = 5), polymeric infant formula (R
      = 6, C = 3) or polymeric infant formula supplemented with CPC (R = 11, C = 6) for
      8 weeks until sacrifice. Clinical outcome measures included weight gain and stool
      consistency. Morphologic measures were intestinal villus height and crypt depth.
      Functional outcome measure was mucosal disaccharidase activity. RESULTS: Resected
      animals fed polymeric infant formula alone had reduced weight gain compared with
      controls fed the same diet (P < 0.005). Despite massive small bowel resection,
      animals fed pig chow or polymeric infant formula supplemented with CPC grew at an
      equivalent rate to controls fed polymeric infant formula alone. Resected animals
      supplemented with CPC had increased villus length and crypt depth in the jejunum
      (P < 0.001) and ileum (P < 0.001) compared with resected animals fed either pig
      chow or polymeric infant formula alone. CONCLUSION: In an animal model of SBS,
      CPC supplementation of polymeric infant formula resulted in normal weight gain
      and features of enhanced morphologic adaptation.

PMID- 15572888
TI  - Meat consumption is positively associated with psychomotor outcome in children up
      to 24 months of age.
AB  - OBJECTIVE: The impact of specific complementary foods on health outcomes has been
      poorly studied. We aimed to determine if meat consumption and breastfeeding
      influence growth and neurocognitive outcome in infants up to 24 months of age.
      METHODS: In a longitudinal cohort study, 144 full-term infants were recruited at
      4 months. Their red and white meat consumption was recorded in sequential 7-day
      weighed food intake diaries at 4, 8, 12, 16, 20 and 24 months. Growth data were
      collected at the same census points as the dietary data. Neurocognitive outcome
      (psychomotor developmental indices and mental developmental indices) derived from
      the Bayley Scales of Infant Development II was measured at 22 months. RESULTS:
      Meat intake from 4-12 months was positively and significantly related to weight
      gain (P < 0.05); further analysis suggested this association might be mediated
      via protein intake but was independent of energy, zinc or iron intake. There was
      no interaction between meat intake and breastfeeding on growth. Meat intake from
      4-12 and 4-16 months was positively and significantly related to psychomotor
      developmental indices (P < 0.02 and 0.013, respectively) but there was no
      association between breastfeeding and psychomotor developmental indices nor any
      interaction between meat intake and breastfeeding. Conversely, breastfeeding was
      positively and significantly related to mental developmental indices (P < 0.01)
      but there was no association between meat intake and mental developmental indices
      nor any interaction between breastfeeding and meat intake. These findings
      remained after adjustment for potential confounding factors. CONCLUSION: Meat
      intake, possibly via its effect on protein intake, is associated with increased
      weight gain in infants up to 12 months of age. Meat intake is also positively
      associated with psychomotor development at 22 months. These findings highlight
      the need for further investigation of the role of complementary foods in relation
      to health outcomes.

PMID- 15572889
TI  - Distribution of sialic acids in the milk of spanish mothers of full term infants
      during lactation.
AB  - OBJECTIVES: The protective effect of human milk against infection is well known.
      Several non-immunologic components, including complex carbohydrates, have been
      described. The present study was undertaken to determine the sialic acid
      distribution in different milk fractions (complex carbohydrates). METHODS: Milk
      samples from 12 Spanish women at three different lactational stages (colostrum,
      transitional milk and mature milk) were analyzed. Total and glycoprotein-bound,
      oligosaccharide-bound, casein-bound, and lipid-bound sialic acids were
      determined. RESULTS: Sialic acids from human milk are mainly bound to
      oligosaccharides and only a small amount is present bound to glycoproteins or in
      the free form. All the fractions analyzed showed a similar trend: sialic acids
      decrease rapidly along lactation. Casein-bound sialic acid does not follow this
      trend. We detected the presence of an O-acetylated species of N-acetylneuraminic
      acid. CONCLUSIONS: In human milk from Spanish women we observed slightly
      different values than those previously reported. This could be a result of
      population differences but nutritional or methodological aspects can not be
      discarded.

PMID- 15572890
TI  - Bone quantitative ultrasound and bone mineral density in children with celiac
      disease.
AB  - OBJECTIVES: Osteoporosis is the most common manifestation of untreated celiac
      disease (CD). Bone quantitative ultrasound (QUS) has recently emerged as a new
      modality for bone status assessment. We evaluated bone status in children with CD
      using dual-energy x-ray absorptiometry and quantitative ultrasound. METHODS: This
      cross-sectional study included 41 children (13 girls, 28 boys) aged 11.2 +/- 3.6
      years with CD. All children had been diagnosed with CD for at least 1 year (mean,
      5.7 +/- 4.3 years). The results of lumbar spine bone mineral density assessed by
      dual-energy x-ray absorptiometry and the measurements of the velocity of
      ultrasound wave (at distal radius and midshaft tibia sites), expressed as speed
      of sound in m/s, were compared between children adherent to gluten-free diet
      (GFD) and non-compliant children. RESULTS: Speed of sound z-scores at tibia were
      below -2 SD in 20 of 41 children (49%), whereas lumbar spine bone mineral density
      z-scores were below -2 SD in 4 of 41 (10%) children with CD (P = 0.0002). Only 19
      of 41 children were strictly compliant to GFD. The prevalence of tibia speed of
      sound z-scores <-2 SD was significantly higher in non-compliant children (15 of
      22, 68%) compared with children on GFD (5 of 19, 26%), (P = 0.01). Children non
      compliant with GFD had significantly worse tibia speed of sound z-scores (-2.3 +/
      1.8, mean +/- SD) compared with children on GFD (-1.2 +/- 1.5, mean +/- SD) (P =
      0.04). CONCLUSIONS: Children with CD on a gluten-containing diet had higher
      prevalence of abnormal tibia bone SOS and lower z-scores compared with children
      on a GFD. These differences were not detected by spinal dual-energy x-ray
      absorptiometry or radius speed of sound. The value of quantitative ultrasound for
      screening and follow-up of children with CD should be further evaluated.

PMID- 15572891
TI  - Clinical case definition for the diagnosis of acute intussusception.
AB  - OBJECTIVE: Because of the reported association between intussusception and a
      rotavirus vaccine, future clinical trials of rotavirus vaccines will need to
      include intussusception surveillance in the evaluation of vaccine safety. The aim
      of this study is to develop and validate a clinical case definition for the
      diagnosis of acute intussusception. METHODS: A clinical case definition for the
      diagnosis of acute intussusception was developed by analysis of an extensive
      literature review that defined the clinical presentation of intussusception in 70
      developed and developing countries. The clinical case definition was then
      assessed for sensitivity and specificity using a retrospective chart review of
      hospital admissions. Sensitivity of the clinical case definition was assessed in
      children diagnosed with intussusception over a 6.5-year period. Specificity was
      assessed in patients aged <2 years admitted with bowel obstruction and in
      patients aged <19 years presenting with symptoms that may occur in
      intussusception. RESULTS: The clinical case definition accurately identified 185
      of 191 assessable cases as "probable" intussusception and six cases as "possible"
      intussusception (sensitivity, 97%). No case of radiologic or surgically proven
      intussusception failed to be identified by the clinical case definition. The
      specificity of the definition in correctly identifying patients who did not have
      intussusception ranged from 87% to 91%. CONCLUSIONS: The clinical case definition
      for intussusception may assist in the prompt identification of patients with
      intussusception and may provide an important tool for the future trials of
      enteric vaccines.

PMID- 15572892
TI  - Comparison of invasive and non-invasive tests diagnosis and monitoring of
      Helicobacter pylori infection in children.
AB  - BACKGROUND: There are few reports which the tests used for diagnosing
      Helicobacter pylori infection and monitoring its eradication in children. STUDY
      AIMS: Prospective evaluation of invasive (gastric histology, rapid urease test
      [RUT]) and non-invasive (stool antigen [FemtoLab H. pylori], urea breath test
      [UBT]) tests in the diagnosis of H. pylori infection and post-treatment
      eradication in children and adolescents. METHODS: Ninety-two patients (50 male,
      42 female) referred for upper gastrointestinal endoscopy were prospectively
      enrolled. UBT was performed and stool specimens collected for monoclonal enzyme
      immunoassay for H. pylori antigen (FemtoLab) 1 to 4 days before endoscopy. H.
      pylori in gastric biopsies was evaluated by RUT and staining with hematoxylin
      eosin and giemsa. Eradication therapy was given to children with abdominal pain
      and H. pylori gastritis. FemtoLab H. pylori and UBT were repeated 6 weeks after
      the end of triple therapy. RESULTS: Histology identified H. pylori in 49 of 92
      (53%) subjects. Concordance between histology and RUT was found in 78 of 92
      children. FemtoLab H. pylori was positive in 41 of 78 (52.6%) children with
      sensitivity, specificity, positive and negative predictive values of 97.5%,
      94.7%, 95.1% and 97.3%, respectively. For UBT, these values were 100%, 96.9%,
      97.5% and 100%, respectively. Twenty-six of 36 patients who received triple
      therapy returned for eradication evaluation. Tests for H. pylori antigen in stool
      were positive in 10 of 26 and for UBT in 11 of 26. CONCLUSION: Stool antigen
      (FemtoLab) and UBT were equally effective in diagnosing and confirming
      eradication of H. pylori infection in children.

PMID- 15572893
TI  - Dynamic color Doppler sonography of intestinal wall in patients with Crohn
      disease compared with healthy subjects.
AB  - OBJECTIVE: Chronic inflammatory bowel diseases are characterized by inflammatory
      hyperperfusion of the intestinal wall in affected bowel segments. We applied a
      novel method to quantify color Doppler signals dynamically along a complete heart
      cycle inside the bowel wall. The aim was to describe bowel wall perfusion in
      Crohn disease patients in comparison with healthy probands and to compare a
      conventional activity index (Pediatric Crohn Disease Activity Index) with
      perfusion measurements as an indicator of inflammatory activity. METHOD: Color
      Doppler sonographic videos of bowel wall perfusion from 34 healthy children (aged
      5 to 18 years) and from 14 patients with Crohn disease (aged 8.2 to 15.9 years)
      were recorded under defined conditions. Perfusion signals (color hue, color area)
      were automatically measured inside the bowel wall. Specific tissue perfusion was
      calculated as mean flow velocity of a region of interest during one full heart
      cycle. Bowel wall perfusion was compared using the Pediatric Crohn Disease
      Activity Index in 12 patients. RESULTS: Specific bowel wall perfusion was
      significantly elevated in bowel segments of Crohn disease patients compared with
      healthy subjects (P < 0.001). Specific flow in small bowel was 0.025 cm/s in
      healthy probands and 0.095 cm/s in patients with Crohn disease, whereas large
      bowel wall perfusion of 0.012 cm/s in healthy probands clearly differed from
      0.082 cm/s in patients with Crohn disease. No differences of perfusion between
      moderate and high Pediatric Crohn Disease Activity Index levels could be
      demonstrated despite a weak significant overall correlation. CONCLUSION: The new
      method of dynamic, automatic noninvasive perfusion quantification is useful to
      describe local inflammatory activity in bowel segments affected by Crohn disease
      and adds new information to activity evaluation by Pediatric Crohn Disease
      Activity Index. Specific wall perfusion in intestines of Crohn patients is
      significantly elevated and reaches up to sevenfold intensity compared with
      healthy subjects.

PMID- 15572894
TI  - Cow's milk allergy in infants with atopic eczema is associated with aberrant
      production of interleukin-4 during oral cow's milk challenge.
AB  - OBJECTIVES: A failure in the establishment and maintenance of oral tolerance in
      infancy may result in food allergy. To further assess the role of the intestinal
      immune system in cow's milk allergy (CMA), we investigated the systemic
      production of the pro-allergenic Th2 cytokine interleukin (IL)-4 and anti
      allergenic cytokines IL-10, transforming growth factor (TGF)-beta1 and TGF-beta2
      in infants suffering from atopic eczema with and without CMA during antigen
      elimination diet and oral antigen exposure. METHODS: 18 infants (mean age, 9.6
      months; 95% confidence interval 8.1-11.1 months) with atopic eczema and CMA and
      17 infants (mean age, 9.7 months; 95% confidence interval 8.6-10.9 months) with
      atopic eczema tolerant to milk as assessed by a double blind, placebo-controlled
      cow's milk challenge were investigated. Peripheral blood mononuclear cells were
      obtained during antigen elimination diet and during oral cow's milk challenge and
      stimulated with Concanavalin-A or cow's milk or were left unstimulated. The
      cytokine concentrations were measured by enzyme-linked immunosorbent assay.
      RESULTS: During antigen elimination, the Concanavalin A-stimulated production of
      TGF-beta2 was significantly lower in infants with CMA as compared with infants
      without CMA: 129 pg/mL (interquartile ratio, 124-144 pg/mL) vs. 149 pg/mL
      (interquartile ratio, 133-169 pg/mL); P = 0.016. During oral antigen exposure,
      the immune responses in infants with CMA were characterized by significantly
      higher spontaneous production of IL-4 as compared with those without CMA: 12.0
      pg/mL (interquartile ratio, 5.2-28.3 pg/mL) vs. 4.2 pg/mL (interquartile ratio,
      1.5-7.6 pg/mL); P = 0.018. CONCLUSIONS: Infants with atopic eczema and CMA
      exhibit markedly increased systemic pro-allergenic IL-4 responses on intestinal
      antigen contact, which may partially be explained by a defective ability to
      launch anti-allergenic TGF-beta2 responses.

PMID- 15572895
TI  - Polyethylene glycol 3350 without electrolytes for the treatment of functional
      constipation in infants and toddlers.
AB  - OBJECTIVES: We have recently reported the safety and efficacy of polyethylene
      glycol 3350 without electrolytes (PEG) for the daily treatment of constipation in
      older children. Because there are very few data available on the use of PEG in
      infants and toddlers, we evaluated the efficacy and safety of PEG for the
      treatment of constipation in children <2 years of age. METHODS: This is a
      retrospective chart review of 75 constipated children <2 years of age at start of
      PEG therapy. PEG was started at an average dose of 1 g/kg body weight/d and
      parents were asked to adjust the dose to yield 1 to 2 soft painless stools/d.
      Data from the history and physical examination were collected initially and at
      short-term (<or=4 months) and long-term (>or=6 months) follow-up. RESULTS: 75
      otherwise healthy children received PEG for functional constipation. The mean age
      was 17 months (range, 1 to 24 months) and the mean duration of constipation was
      10 months (range, 0.5 to 23 months). The mean duration of short-term follow-up
      was 2 months and mean duration of long-term follow-up was 11 months. The mean
      effective short-term PEG dose was 1.1 g/kg body weight/d and the mean long-term
      dose was 0.8 g/kg body weight/d. Constipation was relieved in 85% with short-term
      and in 91% with long-term PEG therapy. Adverse effects were mild and included
      diarrhea, which disappeared with lowering the dose. No subjects stopped PEG
      because of adverse effects. CONCLUSION: PEG is effective, well tolerated and
      appeared safe for the treatment of functional constipation in children <2 years
      of age.

PMID- 15572896
TI  - Association of serum interleukin-8 levels with the degree of fibrosis in infants
      with chronic liver disease.
AB  - OBJECTIVE: Biliary atresia is a neonatal obstructive cholangiopathy characterized
      by a destructive, obliterative process affecting both the intrahepatic and
      extrahepatic ducts of the biliary tree that uniquely presents in the first months
      of life. The consequence of progressive inflammatory and sclerotic reaction is
      the development of obstructive jaundice. To determine the proinflammatory
      cytokine profile in children with biliary atresia, we measured circulating levels
      of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and IL-8. METHODS:
      Twelve children, five males and seven females, with biliary atresia were studied.
      In addition, four patients with progressive familial intrahepatic cholestasis and
      three with Alagille syndrome were also included. Five patients with neonatal
      hepatitis were studied as controls of a liver disease without portal fibrosis.
      Serum concentration of total and conjugated bilirubin, gamma-glutamyl transferase
      and glutamic-pyruvic transaminase were measured by routine methods in all
      patients at time of sampling for the study. The degree of fibrosis in liver
      biopsies was scored using the histologic activity index. RESULTS: In our study IL
      8 was detectable in 11 of 12 patients with biliary atresia with a median level of
      262 pg/ml and a highly statistically significant difference (P < 0.0001) from
      controls. In patients with progressive familial intrahepatic cholestasis or with
      Alagille syndrome serum IL-8 levels were similarly elevated. In patients with
      neonatal hepatitis, IL-8 levels were marginally increased. Serum IL-8 levels were
      significantly correlated (Rs = 0.725, P < 0.0001) with the histologic activity
      index. CONCLUSIONS: Although further studies are needed to determine the role of
      IL-8 in portal inflammation, our results suggest that increased production of IL
      8 may be a mechanism leading to the progressive portal inflammation and fibrosis
      in patients with chronic liver disease.

PMID- 15572897
TI  - The effect of flavoring oral rehydration solution on its composition and
      palatability.
AB  - OBJECTIVE: As a number of mild to moderately dehydrated children refuse to drink
      oral rehydration solution (ORS) because of its strong salty taste, many parents
      and health workers flavor ORS with the childs favorite juice. The effects of
      flavoring ORS on electrolyte content and osmolality were assessed and the
      palatability of various solutions were compared with commercially flavored ORS.
      METHODS: Osmolality, sodium, potassium, chloride and glucose content after
      flavoring with varying concentrations of apple juice, orange juice or orangeade
      was determined. Two of the solutions were offered to 30 children and adults to
      assess palatability. RESULTS: All additions to ORS (apple juice, orange juice or
      orangeade) caused a decrease of sodium (-30 to -53 mmol/L) and chloride (-27 to 
      47 mmol/L) content, whereas osmolality increased to greater than 311 mOsm/kg.
      These homemade oral rehydration solutions did not fulfill ESPGAN criteria for
      ORS, and rehydration will therefore be less effective. The majority of subjects
      also preferred the commercially flavored ORS. CONCLUSION: Only very small amounts
      of apple juice or orange juice can be added to the ORS without significantly
      altering electrolyte composition and osmolality. Palatability, however, does not
      improve compared with commercially flavored ORS. We therefore recommend using
      commercially flavored ORS, the composition of which fulfills ESPGAN criteria.

PMID- 15572898
TI  - Cytapheresis therapy for ulcerative colitis in three pediatric patients.

PMID- 15572899
TI  - Pancreatitis and probable paraneoplastic cholestasis as presenting manifestations
      of pancreatic lymphoma in a child.

PMID- 15572900
TI  - Bilateral atopic cataracts in a child with eosinophilic esophagitis: an
      association to look out for.

PMID- 15572901
TI  - Herpes simplex virus esophagitis in immunocompetent children.
AB  - OBJECTIVES: To review clinical, laboratory, endoscopic and histologic features,
      treatment and outcome of immunocompetent children with Herpes simplex virus
      esophagitis. METHODS: Retrospective analysis of the medical records of six
      children (five males) referred to our unit between 1997-2001. RESULTS: The median
      age at presentation was 4 years. Fever was present in all, odynophagia/dysphagia
      in five, retrosternal pain in four, vomiting in three, drooling in two and
      irritability and drowsiness in one. The median time between the onset of symptoms
      and the diagnosis was 6.5 days. Endoscopy, performed in all, showed friable
      mucosa and erosive-ulcerative involvement, with histology showing inflammation
      and ulcerated esophagitis. Tissue viral culture was performed in five patients
      and was positive in three, and polymerase chain reaction was positive in two of
      four tested. Serology was consistent with primary Herpes simplex virus infection
      in all. All received nasogastric feeding and acyclovir. The outcome was very
      good. CONCLUSIONS: This is an uncommon and under-recognized condition in the
      immunocompetent child. The most common symptoms are sometimes not diagnostic,
      particularly in very young children. The presence of unusual clinical signs may
      lead to a difficult and delayed diagnosis. Treatment with acyclovir may have
      hastened the resolution of symptoms, but a controlled clinical study was not
      performed.

PMID- 15572902
TI  - Gastrointestinal presentation of Langerhans cell histiocytosis in a child with
      perianal skin tags: a case report.

PMID- 15572903
TI  - Serum levels of pepsinogen I, pepsinogen II, and gastrin-17 in the course of
      Helicobacter pylori gastritis in pediatrics.

PMID- 15572904
TI  - Celiac disease is a good disease--HLA association model [corrected].

PMID- 15572905
TI  - Is recurrent abdominal pain of childhood a psychosomatic disorder?

PMID- 15572908
TI  - Fractures and child abuse.

PMID- 15572915
TI  - Giving vancomycin safely.

PMID- 15572918
TI  - Drawing blood culture specimens for reliable results.

PMID- 15572919
TI  - On the march against Legionnaires' disease.

PMID- 15572920
TI  - What are the current Pap test guidelines?

PMID- 15572921
TI  - Myths and facts... about genetic testing.

PMID- 15572938
TI  - A good night's sleep.

PMID- 15572939
TI  - Is your patient depressed?

PMID- 15572940
TI  - Top 10 tips for coping with short-staffing.

PMID- 15572941
TI  - Need urine from a catheter system? Forget the needle!

PMID- 15572943
TI  - Getting the most from your personal protective gear.

PMID- 15572945
TI  - Nit-PICCing over an expert.

PMID- 15572946
TI  - You routinely administer combination drugs ...

PMID- 15572947
TI  - Managing procedural pain.

PMID- 15572948
TI  - Perforated peptic ulcer.

PMID- 15572949
TI  - Memorable medical mentors: VIII. Carl G. Hartman (1879-1968).

PMID- 15572950
TI  - Posthumous sperm procurement: demand and concerns.

PMID- 15572960
TI  - Parathyroid hormone for the treatment of osteoporosis.
AB  - Imbalances in bone metabolism result in bone mass loss and skeletal fragility in
      postmenopausal women and older men. Most osteoporosis treatments decrease bone
      metabolism and prevent the progression of bone loss and architectural damage to
      the skeleton. Analogs of parathyroid hormone stimulate the formation of new bone
      and offer new options for managing osteoporosis. This review highlights the
      effects of parathyroid hormone on bone density and fracture risk in patients with
      osteoporosis and addresses several of the important issues pertaining to the use
      of these new agents in daily clinical practice. TARGET AUDIENCE: Obstetricians
      and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of
      this article, the reader should be able to summarize the different mechanisms of
      action between parathyroid hormone analogues and antiresorptive drugs, to outline
      the effects of teriparatide treatment of patients with osteoporosis, and list the
      indications of teriparatide therapy.

PMID- 15572961
TI  - Infectious necrosis with dehiscence of the uterine repair complicating cesarean
      delivery: a review.
AB  - The authors summarize current knowledge about infectious uterine incisional
      necrosis/dehiscence, an uncommon but serious complication of cesarean delivery. A
      MEDLINE search of the literature from 1966 to the present did not identify any
      previous review of this entity. From case reports, small case series, and
      textbook descriptions, the evidence regarding the definition of the disorder, its
      prevalence, etiology, pathogenesis, diagnosis, prognosis, and management is
      presented. The paucity of reports in the modern literature indicate the need for
      further studies to more precisely characterize this entity for cross-study
      comparisons and aggregation to provide clearer management guidelines, especially
      as it regards diagnosis, and the safety of conservative surgery in well-selected
      cases. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.
      LEARNING OBJECTIVES: After completion of this article, the reader should be able
      to define the condition infectious uterine incisional necrosis, and to outline
      potential management options.

PMID- 15572962
TI  - HELLP syndrome: the state of the art.
AB  - Preeclampsia/eclampsia has been recognized for centuries and continues to plague
      both the patient and the obstetrician. A severe variant, the syndrome of
      hemolysis, elevated liver enzymes, and low platelets (HELLP), has been recognized
      for 50 years. Although much new data has been elucidated about the condition,
      only several observations have withstood the test of time. These are the
      uniqueness of the disease to humans, the progressive nature of the disease, and
      the fact that delivery is the sole therapy. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this
      article, the reader should be able to outline the history of HELLP syndrome and
      describe the pathophysiology of HELLP syndrome, to summarize the clinical
      presentation and differential diagnosis of HELLP syndrome, and to list the
      various management options.

PMID- 15572966
TI  - The effect of fasting practice on sedation with chloral hydrate.
AB  - OBJECTIVES: Infants undergo various painless imaging procedures frequently. Mild
      sedation is required in such cases to reduce anxiety as well as to ensure optimal
      performance of the procedure. The most frequently used sedative as a single drug
      is chloral hydrate. The issue of preprocedural fasting is a subject of
      contention. The purpose of this study was to assess the effect of the American
      Academy of Pediatrics (AAP)/American Society of Anesthesiology (ASA) fasting
      practice guidelines on the efficacy and success of the sedation with chloral
      hydrate. METHODS: The sedation records of 200 infants from 2 hospitals who
      underwent auditory brainstem response for evaluation of hearing loss were
      evaluated retrospectively. In the first hospital (group A), strict nulla per os
      (NPO) guidelines were followed in accordance with the guidelines published by the
      AAP/ASA, whereas in the second hospital (group B), no fasting period was
      required. All children were premedicated with chloral hydrate. We evaluated the
      sedation failure rate, total dose of chloral hydrate needed, adverse effects,
      overall sleep time, and time to discharge. RESULTS: The average fasting period as
      expected was significantly longer in group A patients than in group B patients
      (5.7 +/- 1.7 vs. 2 +/- 0.2 hours; P < 0.001). Group A patients demonstrated a
      significantly higher failure rate to achieve sedation with the first dose of
      chloral hydrate compared with group B patients (21% vs.11%; P = 0.03), hence
      needing higher doses (83 +/- 31 vs. 61 +/- 21 mg/kg; P < 0.01), and were sedated
      for longer periods (103 +/- 42 vs. 73 +/- 48 minutes; P < 0.001) and discharged
      later. No difference was found in the adverse effect rate. CONCLUSION: Fasting
      was associated with an increased failure rate of the initial sedation. As a
      consequence, an increased total dose of chloral hydrate was required inducing a
      prolonged sedation time. Presumably, this is a result of the fact that a hungry
      child is irritable and therefore more difficult to sedate.

PMID- 15572967
TI  - Pediatric first aid knowledge among parents.
AB  - OBJECTIVE: The American Academy of Pediatrics (AAP) has published simple
      guidelines for the first aid management of ill or injured children. We determined
      knowledge of these first aid practices in parents. METHODS: Design-Descriptive
      survey. PARTICIPANTS: A convenience sample of adult parents presenting to the
      emergency department. SURVEY INSTRUMENT: Standardized collection of demographics
      was performed and adults were given a multiple-choice questionnaire concerning
      the proper management of stings and bites, burns and scalds, eye injuries,
      fractures and sprains, fever, head injuries, fainting, poisoning, dental
      emergencies, nosebleeds, seizures, and skin wounds. OUTCOMES: Percentage of
      adults responding to questions appropriately based on AAP guidelines. DATA
      ANALYSIS: Descriptive statistics and chi2 tests. RESULTS: Six hundred fifty-four
      adults were surveyed. Mean age (SD) was 38.5 (13.8), 56% were female, 69% were
      white, 56% had at least a high school education. None of those surveyed answered
      all questions correctly with roughly half being familiar with 60% of the
      questions. Knowledge of specific guidelines ranged from 21% to 92%. Subjects
      especially lacked knowledge regarding the need to rapidly remove all bee stingers
      (only 36% aware); keep wounds moist and covered (79% felt that drying wounds was
      beneficial); the need to cover victims of large burns (only 43% aware); and the
      need to seek medical attention after tick bites (only 47% aware). Knowledge was
      unaffected by age, gender, and education. CONCLUSIONS: Many adults are unfamiliar
      with AAP first aid measures according to the AAP guidelines and most believe that
      wounds should be allowed to dry. Further education is required to improve
      knowledge of first aid practices.

PMID- 15572968
TI  - The anesthetic effectiveness of lidocaine-adrenaline-tetracaine gel on finger
      lacerations.
AB  - OBJECTIVES: To determine the effectiveness of lidocaine-adrenaline-tetracaine
      (LAT) in providing adequate anesthesia for the repair of finger lacerations and
      to monitor the risk of digital ischemia following application of LAT gel to
      finger lacerations. METHODS: A prospective case series. Children aged 5 to 18
      years with a simple finger laceration-requiring repair were eligible for
      enrollment. The primary outcome measure was LAT success/failure. Failure was
      defined as any sharp sensation reported by the patient either before or during
      suturing. Enrolled patients had LAT gel applied to their laceration for 45
      minutes, followed by an examination for signs of digital ischemia and standard
      laceration repair. Infiltration anesthesia (local subcutaneous injection/digital
      block) was provided for all LAT failures. Patients were followed up by phone
      within 3 to 5 days from discharge. RESULTS: Sixty-seven patients were analyzed in
      the study. The mean age was 11.9 years. Forty-four (65.7%) of 67 patients were
      male and 46 (68.7%) were white. Locations of the lacerations were equally
      distributed on the dorsal and ventral surfaces. The overall LAT success rate was
      53.7% (95% confidence interval [CI], 41.1% to 66.0%; 36/67). The success rate for
      dorsal surface lacerations was 68.6% (95% CI, 50.7% to 83.1%; 24/35) versus 37.5%
      (95% CI, 21.1% to 56.3%; 12/32) for ventral surface lacerations. The difference
      in success rates between dorsal and ventral surface lacerations was significant
      (Delta 31.1% [95% CI, 8.3% to 53.8%]). There were no differences in success rates
      for age, sex, or race. No signs of digital ischemia were noted in any of the 67
      cases (0% [95% CI, 0.0% to 5.4%]). CONCLUSIONS: LAT gel appears to be a safe and
      effective means of providing anesthesia for the repair of simple finger
      lacerations in children. It was most effective on the dorsal surface of the
      finger.

PMID- 15572969
TI  - Pain, position, and stylet styles: infant lumbar puncture practices of pediatric
      emergency attending physicians.
AB  - OBJECTIVES: Lumbar punctures (LPs) are common emergency department (ED)
      procedures. Few pediatric studies exist to define training, guide practice, or
      indicate preferred methods for infants. While pain control is recommended, no
      recent studies indicate prevalence of analgesic use since the advent of topical
      anesthetics. We surveyed academic pediatric ED physicians to assess training and
      technique preferences and to highlight pain control usage. METHODS: A total of
      398 physicians were randomly selected from the 621 e-mail accessible members of
      the AAP Section on Pediatric Emergency Medicine. Questions concerning physician
      training, analgesia, and technique were either sent by regular mail or via e-mail
      link to a Web-based survey. RESULTS: Of 359 deliverable surveys, there were 188
      physician responses (52.4%) with differential response rates by survey format [58
      e-mail (36%) and 130 regular mail responses (66%); P < 0.05]. Almost a third will
      advance the needle without the stylet in place. Two-thirds of physicians do not
      routinely use analgesia for neonatal LPs. Those using pain control were trained
      more recently (median 12 years vs. 15 years postresidency; P = 0.04). Analgesia
      use was the most common practice changed since residency. CONCLUSIONS: Analgesia
      is underused for infant LPs. Advancing the needle without a stylet is not
      uncommon. Response rate to regular mail surveys was much higher.

PMID- 15572970
TI  - Subgaleal hematoma from hair braiding: case report and literature review.

PMID- 15572971
TI  - Unsuspected acetaminophen toxicity in a 58-day-old infant.
AB  - Acetaminophen is frequently used by both physicians and parents for the relief of
      pain and fever in infants and children of all age groups. It has an excellent
      safety profile in therapeutic doses, but hepatotoxicity can develop following
      both intentional or unintentional overdoses. Repetitive doses of acetaminophen,
      usually in supratherapeutic amounts, but not always, in ill infants have been
      associated with hepatotoxicity. Acetaminophen toxicity may be very difficult to
      diagnose in young infants when suspicion for this entity is low. In addition,
      initial signs and symptoms are nonspecific and biochemical evidence of hepatic
      damage may not become evident for 24 to 36 hours. We report the case of an infant
      who received multiple doses of acetaminophen during an illness who developed
      hepatotoxicity.

PMID- 15572972
TI  - Fictitious fracture after infusion of intravenous contrast material via an
      intraosseous needle.

PMID- 15572973
TI  - "I can't taste ice cream": an unusual case of tinnitus and dysgeusia.
AB  - Auricular foreign bodies are usually presented to the emergency department in an
      easily recognizable fashion. We report the case of a 16-year-old male who
      presented to the emergency department with complaints of unilateral tinnitus and
      dysgeusia. He denied any history of injury except for falling from his bike in
      the woods earlier that day. On examination, a wooden foreign body was found in
      the external auditory canal. A computed tomography scan revealed a 3-cm-long twig
      that pierced the middle ear disrupting the ossicles. He was taken to the
      operating room for removal and microscopic evaluation. On evaluation, the chorda
      tympani nerve was found to be severed along with disruption of the ossicles. This
      is an unusual presentation for an aural foreign body, and the resulting injury of
      the chorda tympani is not well published. One should consider the possibility of
      injury to the middle and inner ear and perform the necessary clinical evaluation
      before and after removal of aural foreign bodies.

PMID- 15572974
TI  - Recurrent abdominal pain: more acute and worse today.

PMID- 15572975
TI  - ED-PICU collaboration: getting by with a little help from our friends.

PMID- 15572976
TI  - An exceedingly agitated patient.

PMID- 15572977
TI  - ECGs in the ED.

PMID- 15572978
TI  - Atopic dermatitis and treatment with topical immunomodulators.

PMID- 15572980
TI  - Dextromethorphan abuse.
AB  - Dextromethorphan is an over-the-counter dissociative agent of increasing
      popularity as a drug of abuse among younger adolescents. The drug produces a
      range of toxicities depending upon either the dose or the components of the
      specific formulation that was ingested. Most cases improve with supportive care
      alone, but severely intoxicated patients may require significant attention.
      Because dextromethorphan is misused primarily by younger adolescents, the early
      identification and treatment of dextromethorphan abuse may be important in
      preventing broader substance abuse in these children. Consequently, it is
      important for clinicians to recognize, treat, and appropriately refer those who
      present with intoxication from this drug.

PMID- 15572983
TI  - Apparent life-threatening event, not acute.

PMID- 15572982
TI  - An animal model of the childhood accidental spiral tibial fracture.

PMID- 15572987
TI  - Functional outcome following traumatic brain injury: the Turkish experience.
AB  - The objectives of this study were to describe the demographic characteristics and
      the nature of the functional recovery in a group of Turkish survivors of
      traumatic brain injury (TBI) who were referred for inpatient rehabilitation and
      identify variables correlated with discharge functional status as measured by the
      Functional Independence Measure (FIM). There were 40 patients in the study, 32
      (69.6%) male and eight (17.4%) female, mean age 28+/-9.8 years. Motor vehicle
      accidents accounted for 62.5% of injuries, 22.5% of injuries occurred from
      violence and 15% resulted from falls. The mean durations of acute hospital stay,
      coma, and rehabilitation stay was 68, 26.7, and 78.4 days, respectively.
      Extracranial injuries including bone fractures were the most common associated
      injuries and medical complications such as spasticity and contractures were
      present in more than half of the patients.TBI survivors in this study made
      statistically significant functional improvements. Discharge FIM were
      significantly correlated with the admission FIM, durations of acute hospital stay
      and coma, and time since TBI. Multiple regression analysis of the data disclosed
      that FIM score obtained at the time of discharge from rehabilitation service was
      best predicted by two variables, time since brain injury and the FIM score at
      admission (multiple R=0.78, R=0.60, P<0.001). This sample of Turkish TBI
      survivors showed significant functional improvements after rehabilitation and
      admission functional status and the time since TBI had the most impact on
      discharge functional outcome.

PMID- 15572988
TI  - The cross-cultural adaptation of the Work Role Functioning Questionnaire in
      Canadian French.
AB  - The Work Role Functioning Questionnaire (WRFQ) is a new work disability
      measurement tool assessing the perceived impact of a health problem on the
      worker's ability to perform his job. The objective of this study was to make the
      cross-cultural adaptation of the WRFQ for the French Canadian population. The
      methodology was composed of five steps: forward translation, synthesis of the
      translations, back translation, revision by an expert committee and test of the
      pre-final version. The psychometric properties of the translated version were
      evaluated by administering the questionnaire to forty workers with a
      musculoskeletal disorder (MSD). Results indicated good content validity and
      internal consistency (Cronbach alpha > 0.80 for each scale). Construct validity
      was tested and confirmed through three hypotheses: (1) subjects with MSD scored
      higher for the Physical, Work Scheduling and Output demands scales than for the
      Mental and Social demands scales, (2) subjects having back pain had lower scores
      than subjects having pain at other body sites and (3) subjects with an MSD had
      lower scores than healthy workers working full time. This study confirmed that
      the process used for the adaptation of the Canadian French version of the WRFQ
      was successful and that this version had good psychometric properties.

PMID- 15572989
TI  - Evidence-based practice and rehabilitation: occupational therapy in Australia and
      New Zealand experiences.
AB  - Evidence-based practice has become the dominant paradigm in the delivery of
      rehabilitation programme. However, occupational therapists in Australia and New
      Zealand have been slow in making the transition to become evidence-based
      practitioners. Collaboration between the university/tertiary institute and
      clinical setting is one way that clinicians can be assisted with incorporating
      research into their practice. Two case examples are presented outlining how
      collaborative practice can result in improved outcomes for all concerned.

PMID- 15572990
TI  - The effect of botulinum toxin type-A injection on spasticity, range of motion and
      gait patterns in children with spastic diplegic cerebral palsy: an Egyptian
      study.
AB  - Spasticity is defined as increased resistance to passive movement, secondary to
      hyperreflexia after an upper motor neuron lesion. In children with cerebral palsy
      (CP), it can interfere with mobility and self-care and can contribute to
      development of fixed myostatic contractures. This study investigated the efficacy
      of botulinum toxin type-A, a neuromuscular blocking agent that reduces muscle
      tone, in a variety of neuromuscular disorders, injections in a prospective, 3
      month, controlled study involving 40 children with spastic diplegic CP. The
      patients were divided into two groups: Group 1 (20 patients) entered a botulinum
      toxin type-A injection+physiotherapy rehabilitation program; Group 2 (20
      patients) were given the physiotherapy rehabilitation program only. Patients were
      assessed at 4, 8 and 12 weeks post-treatment using the Modified Ashworth Scale
      (MAS), dynamic gait pattern, ankle range-of-motion measurements and
      quantification of muscle denervation by nerve conduction techniques. The
      botulinum toxin type-A group demonstrated statistically significantly decreased
      spasticity, improved gait function and improved range of motion with evidence of
      partial denervation of the injected muscle compared to the control group. In
      conclusion, botulinum toxin type-A injections are a well-tolerated, non-surgical
      technique that can improve overall response to physiotherapy.

PMID- 15572991
TI  - The effects of seating position on the respiratory patterns of preschoolers with
      cerebral palsy.
AB  - This study investigated the respiratory patterns in upright and semi-reclining
      seating positions in 10 preschoolers with cerebral palsy (CP) and 10 typical
      children. The duration of inhalation, exhalation, total cycle, subcycles and
      phase lags were calculated during rest and during imitation of 3-, 7-, and 10
      syllable utterances on one breath. The Respitrace was used to gather respiratory
      data on duration and chest wall usage. Tidal breathing demonstrated a faster rate
      of breathing in reclining for both groups. A difference between the groups in the
      use of the regions of the chest wall was also evident with the CP group having
      longer abdominal cycles than the control group. During speech, the groups
      differed in duration of respiratory cycle and region initiating movement. The
      duration of the 3- and 7-syllable tasks were significantly longer for the group
      with cerebral palsy. Indications of strategies to control the recoil forces of
      the chest wall for speech are discussed.

PMID- 15572992
TI  - Leisure activities, friendships, and quality of life of persons with intellectual
      disability: foster homes vs community residential settings.
AB  - Living in the community does not, in itself, guarantee social integration and
      inclusion for persons with intellectual disability. Friendships and leisure
      participation can indicate the beginning of such a process and their impact on
      quality of life. The present study investigated the quality of life, friendships
      and leisure activities of persons with intellectual disability who live in
      community settings or in foster families. Three hypotheses were examined: 1.
      Persons with intellectual disability who live in foster families have more
      friends than do those who live in community residential settings. 2. Persons with
      intellectual disability who live in community residential settings participate in
      more leisure activities than those who live in foster families. 3. The more
      friendships and leisure activities in which one is involved, the higher the
      quality of one's life. The sample consisted of 85 adults with intellectual
      disability, ranging in age from 18 to 55 years. Forty-five live in community
      residential settings and 40 live in foster families in Israel. Five
      questionnaires were used: 1) a demographic questionnaire; 2) Quality of Life
      Questionnaire, 1990); 3) the Revised UCLA Loneliness Scale; 4) Social
      Relationships List; and 5) Leisure Activities List. The main findings show no
      significant differences between the two groups in the number of friendships or
      feelings of loneliness. Foster residents were more involved and more independent
      in their leisure activities than were those who live in community residences. An
      association between friendships, leisure activities and quality of life was
      partly confirmed. The need for intervention programs and leisure education
      programs is discussed.

PMID- 15572993
TI  - A pilot study to investigate the effect of lumbar stabilisation exercise training
      on functional ability and quality of life in patients with chronic low back pain.
AB  - In recent times lumbar stabilisation programmes, targeting the local stabilisers
      in the lumbar region, have increased in popularity in the treatment of chronic
      low back pain (CLBP) yet their effectiveness in enhancing quality of life remains
      unclear. The objective of this pilot study was to examine the effectiveness of a
      programme of lumbar stabilisation exercises in improving quality of life and
      functional outcomes in patients with CLBP. Forty-one patients with CLBP who
      volunteered to take part in the study were randomly assigned to a treatment group
      (n=20) or a control group (n=21). The treatment group underwent a 10-week lumbar
      stabilisation programme whilst the control group received no intervention. The
      Roland Disability Questionnaire, Oswestry Disability Questionnaire and the SF-36
      survey were administered to subjects in both groups at baseline and follow-up.
      Significant improvements were seen in all measures in the treatment group whereas
      control subjects demonstrated either no change or a significant worsening
      (P<0.05). These results suggest that a programme of lumbar stabilisation is
      effective in improving quality of life and functional outcome in patients with
      CLBP.

PMID- 15572994
TI  - Tai Chi Chuan practice in community-dwelling persons after stroke.
AB  - Eighteen community-dwelling first-stroke survivors, aged 45 to 65, underwent
      following examinations: Romberg's Test, standing on the unaffected leg, Emory
      Fractional Ambulation Profile, the Berg Balance Test, the Timed 'Up and Go' Test
      and the Duke Health Profile. They were then randomly divided into two matched
      groups of 9 subjects each. The study group (SG) received Tai Chi exercises and
      the control group (CG) physiotherapy exercises focused on improvement of balance,
      both groups for 1 h twice weekly for 12 weeks. On completion of exercises, SG
      subjects showed improvement in social and general functioning whereas CG subjects
      showed improvement in balance and speed of walking. It is concluded that there
      are potential and no adverse effects in Tai Chi practice in stroke survivors.

PMID- 15572995
TI  - Statistical assessment of changes in ADL dependence: three-graded versus
      dichotomised scaling.
AB  - The aim of this study was to investigate how dichotomising three-graded ADL
      Staircase data affects the possibility of detecting changes in ADL dependence
      between different assessment occasions. An authentic two-occasion data set was
      used as a basis for a simulation experiment. In all, we used four different data
      treatment principles, all utilising the matched pairing of the data. The first
      principle utilised a sum score technique, and the second within-person
      comparisons by means of item-by-item analysis of improvement or deterioration.
      The third principle used ADL ranks, a novel approach, while the fourth used
      within-item ranks. Independently of the data treatment principle used, the
      statistical power of all tests was reduced by 13-24% after dichotomisation,
      compared to when the three-graded scale was utilised. The results indicate that
      dichotomising ADL Staircase data results in information loss, and hence in
      reduced ability to detect changes. The need to consider the purpose of the ADL
      assessment before reducing the number of scale steps is highlighted. The
      knowledge generated in this study is useful for practitioners and researchers,
      aiming at evaluating rehabilitation interventions.

PMID- 15572996
TI  - Reducing inpatient hospital usage for management of pressure sores after spinal
      cord lesions.
AB  - Recurrent pressure sores are a devastating complication for people with spinal
      cord lesions as well as posing a drain on health resources. A programme of
      community outreach involving the long-term follow-up of people post
      hospitalisation for severe pressure sores has been developed in Queensland,
      Australia. This service is known as SPOT (Spinal Outreach Team). The primary
      objective of this follow-up is to prevent recurrence of pressure sores where
      possible or alternatively to detect problems early so that rehospitalisation is
      avoided. In order to assess the effectiveness of this programme the readmission
      patterns of 14 patients with recurrent pressure sores were examined. The mean
      number of hospitalised days per patient per month were examined between 1991 and
      2001. Three phases within this time frame were examined 1991-1995, no SPOT
      service; 1996-1998, generic SPOT service (without individual interventions) and
      1999-January 2002, individualised SPOT programmes for high users. Hospital days
      per patient per month were significantly lower for the individualised phase than
      for the other two phases combined. Proactive, individually tailored approaches
      are recommended for individuals at high risk of readmission for pressure sores.

PMID- 15572997
TI  - The right to equal opportunity and treatment: employment of persons with
      disabilities in Slovenia.
AB  - The article presents a brief description of the research carried out at the
      Institute for Rehabilitation in 2002/2003. In the first part of the article,
      policies, programmes and measures for promoting vocational rehabilitation and
      employment of persons with disabilities adopted by Slovenia in the period 1999
      2002 are analysed. The key finding is that the situation of persons with
      disabilities in the labour market is significantly weaker than that of the non
      disabled. The second part includes the empirical part of the research and
      addresses the problem of the attitudes of the employers towards the employment of
      persons with disabilities.

PMID- 15572998
TI  - Arm-crank propelled three-wheeled chair: physiological evaluation of the
      propulsion using one arm and both arm patterns.
AB  - Disabled people in India frequently use the arm-crank propelled three-wheeled
      chair (ACWC) for outdoor transportation. Two models of these chairs are
      commercially available: one is powered by cranking using one arm (ACWC-1) and the
      other uses both arms (ACWC-2). The purpose of the study was to compare the
      efficiency of the two types of propulsion with respect to the standard
      physiological responses and, consequent upon the findings, to recommend the use
      of a suitable one. The energetics of locomotion of the users at their freely
      chosen speed (FCS) were measured and compared with changes in the physiological
      parameters in the within-subject groups. The study was conducted in outdoor
      settings to simulate the actual locomotive conditions encountered by the users in
      their practical life. 14 males, who had been regular and proficient users of both
      propulsion systems for more than last six years and who had a history of
      paraplegia (below the 10th thoracic vertebra, n=11) and poliomyelitis (n=3)
      participated in the study. The subjects were required to propel the test chair (a
      combination of both the propulsion systems built in a single model) on an oval
      track of 358 m circumference at their FCS for 5 min; ambulatory data were
      collected during last 3 min of exercise and averaged. The FCS (m/min), heart
      rates (bpm) and oxygen uptake (l/min) were measured. Physiological cost index
      (b/m) oxygen consumption (ml/kg/min), oxygen cost (ml/kg/m) and net locomotor
      energy cost (kcal/kg/km) of the two sets of observations were derived and
      compared using a t-test for the paired observations. The FCS was significantly
      higher and the physiological parameters were lower with the ACWC-2 than with ACWC
      1, except for heart rate and oxygen consumption, where the difference was not
      significant . It is concluded that two-arm use is more efficient and less
      physically demanding than one-arm use in the arm-crank propulsion system and that
      the former is more suitable for efficient ambulation.

PMID- 15572999
TI  - Assessment of feeding performance in patients with cerebral palsy.
AB  - Patients with cerebral palsy (CP) frequently manifest oral-ingestive problems
      ranging from mild to severe. Drooling, rejection of solid foods, choking,
      coughing and spillage during eating may contribute to these problems. The aim of
      this study was to assess functional feeding skills of patients with CP, aged 4-25
      years. They were assessed with the Modified Functional Feeding Assessment Scale
      (FFAm). Mothers had expressed concern regarding drooling and reluctance in
      accepting solid foods. None of the mothers thought that there was a major problem
      with adequate ingestion. However, the study revealed that patients had
      disabilities in spoon feeding, biting, chewing, cup drinking, straw drinking,
      swallowing and clearing.

PMID- 15573000
TI  - Life skills and subjective well-being of people with disabilities: a canonical
      correlation analysis.
AB  - This study examined the canonical relationships between a set of life skill
      variables and a set of subjective well-being variables among a national sample of
      vocational rehabilitation clients in the USA. Self-direction, work tolerance,
      general employability, and self-care were related to physical, family and social,
      and financial well-being. This analysis also found that communication skill is
      related to family and social well-being, while psychological well-being is not
      related to any life skills in the set. The results showed that vocational
      rehabilitation services aimed to improve life functioning will lead to an
      improvement in subjective quality of life.

PMID- 15573001
TI  - New functional vibratory stimulation device for extremities in patients with
      stroke.
AB  - The utility of a new device that delivers functional vibratory stimulation to the
      extremities was studied in 13 patients with stroke. We hypothesized that
      vibratory stimulation of the hemiplegic lower limb would increase gait speed in
      these patients. The device consisted of one battery, two small vibrators and a
      connecting wire. The small vibrators were stabilized on the anterior tibial
      muscle and gluteus medius muscle by a bandage. An analysis of the effects of
      functional vibratory stimulation on hemiplegic lower limb on gait speed indicated
      that gait speed was greater during stimulation than without. These results
      suggest that the new device of functional vibratory stimulation is useful for
      treatment in patients with stroke.

PMID- 15573002
TI  - Nancy Roper (1918-2004): a great nursing pioneer.

PMID- 15573003
TI  - Equality and the children's National Service Framework.

PMID- 15573004
TI  - Quality-of-life and asthma control with low-dose inhaled corticosteroids.
AB  - Guidelines are available to assist healthcare professionals in the appropriate
      management of patients with asthma, a highly prevalent and debilitating disease.
      Despite these guidelines many patients are still not being optimally treated,
      often resulting in poor asthma control and consequent impact on health-related
      quality of life (HRQoL). The present study concerns the findings of a
      multinational survey designed to evaluate the reported level of asthma control
      and HRQoL of patients with asthma. This analysis focuses on those patients
      receiving treatment with low-dose inhaled corticosteroids (ICS) alone. The
      findings confirm that many patients on a low-dose ICS alone are not receiving
      appropriate treatment to control their asthma, and this has a marked negative
      impact on their HRQoL. Revising management and treatment can improve asthma
      control and HRQoL for these patients, liberating them from the burden of this
      disease.

PMID- 15573005
TI  - Pharmacological approaches to stable chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) causes disabling, slowly progressive
      breathlessness on exertion, chronic cough and sputum production. Its natural
      history is punctuated by increasingly frequent exacerbations which in turn
      accelerate disease progression and reduce a patient's quality of life. COPD has
      previously been ignored in the mistaken belief that nothing could be done. There
      are now a number of therapies that can be used to reduce symptoms and prevent
      exacerbations. In turn this reduces disability, improves the patient's health
      related quality of life and has the potential to reduce costs to the health
      service and to society.

PMID- 15573006
TI  - Supporting parents in managing drugs for children with cystic fibrosis.
AB  - A semi-structured interview guide was used to interview 17 parents of children
      with cystic fibrosis identified through a shared care patient database at a
      London hospital to examine parents' medication-related roles and problems.
      Parents described their responsibilities in the home and the problems
      experienced, including adherence to regiments, involvement in decision-making,
      and relationships with the hospital teams and other healthcare professionals. The
      findings confirmed medication management as an integral part of the informal
      caring role. Many practical problems of ensuring the availability and
      administration of medication on a regular basis were described. Information gaps
      and problems with medication adherence increased the stress of providing
      effective care. The involvement of healthcare professionals across primary,
      secondary and tertiary care sectors in supporting parents in all aspects of
      medication management, including the development of strategies for transferring
      the responsibility for medication to their children, must be improved.

PMID- 15573007
TI  - The puzzle of spirituality for nursing: a guide to practical assessment.
AB  - Increasingly nurses are called upon to meet patients' spiritual needs. However,
      there is evidence to suggest that nurses are unable to do this adequately because
      of confusion about the notion of spirituality. This is compounded by the
      uncertainty surrounding the role of nurses in spiritual care interventions.
      Emerging research suggests that nurses, as primary carers, may have to initiate
      spiritual care interventions. This article offers practical guidance to nurses
      seeking to improve spiritual care for their patients. A working definition of
      spirituality is offered and spiritual needs are explained in the context of a
      case scenario. Practical guidance is given on how spiritual care can be put into
      action, using the Actioning Spirituality and Spiritual care in Education Training
      (ASSET) model as a framework for assessment of spiritual needs, planning,
      implementing and evaluation spiritual care, and a spiritual assessment tool for
      practice is outlined.

PMID- 15573008
TI  - Incompetent nurse who failed to acknowledge her limitations.

PMID- 15573010
TI  - The coroner's jurisdiction 1: the current law in the UK.

PMID- 15573009
TI  - Occupational exposure of staff to HIV and prophylaxis therapy.
AB  - Often the provision of post-exposure prophylaxis (PEP) is after exposure to
      persons with an undetermined human immunodeficiency virus (HIV) status. Cases of
      occupationally acquired HIV infection have been documented. The risk of
      contracting HIV from percutaneous exposure is small and PEP can significantly
      reduce the rate of occupational transmission. The Department of Health recommends
      that PEP be considered whenever there is significant exposure to high-risk body
      fluids, e.g. blood or other high-risk body fluids such as synovial or
      cerebrospinal fluid. It is important that a risk assessment is conducted to
      ascertain if the exposure is deemed significant. If it is, in an ideal situation,
      PEP should be commenced immediately, preferably within 1 hour; however, starting
      PEP up to 2 weeks after exposure may still be beneficial. All NHS and other
      healthcare settings, including the independent/private sectors, should ensure
      that they have policies and procedures in place to ensure that their staff are
      aware of the actions to be taken if they are at risk of occupational exposure to
      HIV.

PMID- 15573011
TI  - The role of the healthcare assistant in nursing.

PMID- 15573012
TI  - Pressure ulcer research: where do we go from here?
AB  - The physiology and pathology of pressure defence mechanisms have been little
      studied and are not understood. No critical risk factors have been identified and
      populations of patients identified as being 'at risk' by risk calculators and
      clinical impression often have small numbers of patients who are really
      susceptible to pressure ulcers (PUs). Prevention trials must therefore have large
      sample sizes to enable significant results to be observed, or must be carried out
      in patient populations with a high PU incidence. Many trials have been carried
      out in orthopaedic patients but results may not be generalizable. Measurement of
      physical parameters (e.g. interface pressure), useful for adapting support
      surfaces for individual patients and designing new support systems, is unlikely
      to identify the aetiology of PUs and, without validation from clinical trials,
      predict the efficacy of interventions. In future it may be better to sample other
      groups, such as critical care patients for trials, as the findings might prove
      more generalizable. The effects of interventions should also be researched at the
      healthcare system level rather than that of product or risk factor. However, only
      the physiological study of PU aetiology is likely to advance our knowledge and
      ability to prevent PUs more effectively.

PMID- 15573013
TI  - Nutrition 1: a vital consideration in the management of skin wounds.
AB  - Nutrition is a provocative subject in tissue repair, particularly in relation to
      the skin which consists of many different tissues fulfilling various essential
      functions. This article, the first in a two-part series, will discuss the
      structure of the human skin and its variations, with indications as to the
      individual requirements of the cells in fulfilling their normal role in skin
      physiology and in repair systems. Nutrient gradients seem to play a major role in
      normal skin physiology and repair systems following injury. The second part will
      discuss in more detail the importance of major nutrient factors and their inter
      relationships in tissue repair. It is clear that much of our available knowledge
      is derived from experimental studies in animals. Their relevance in human wound
      healing may be equivocal as the human skin is unique in the animal kingdom.

PMID- 15573014
TI  - Who is leading guideline development in tissue viability?

PMID- 15573015
TI  - The relationship between pain and leg ulcers: a critical review.
AB  - Leg ulceration may have a profound impact on the individual: in some cases
      activities of living become subservient to the degree of pain experienced. Pain
      control, which is viewed as a key function in health care, appears marginalized
      in leg ulcer management. Pain can be intense, bringing psychological implications
      for the patient. Knowledge deficiency in practitioners' management of venous and
      arterial leg ulcers was identified in the literature. This may lead to
      unnecessary pain caused by inappropriate dressings, misdiagnosis, or poor
      technique in the use of compression therapy. A holistic approach to the patient
      using evidence-based standardized practice may improve the patient's experience.

PMID- 15573016
TI  - An online ordering system for therapy beds and mattresses.
AB  - Within this article, the authors have put forward a solution to keep track of
      pressure-relieving devices using internet-based secure online systems. In
      partnership with a therapy bed company they set up a system that was able to
      manage and monitor the requirements of their trust and ensure that products are
      used for patients who most need them. In using these systems they were also able
      to gather real-time data on usage and costs as well as time-dependent analysis.
      The system has also allowed a means of gathering outcome measurement of all
      products in use. Over a 6-month period the authors have shown how a forecasted
      18% budget deficit has been turned into a 10% under spend of the overall budget.
      It is suggested that these systems could be one way of managing the pressure
      relieving needs of hospital trusts ensuring both clinical effectiveness and cost
      benefit.

PMID- 15573017
TI  - The analgesic effect of odour and music upon dressing change.
AB  - Vascular wounds may require frequent dressing changes over a long period of time,
      often involving pain, which may not be adequately controlled with conventional
      analgesia. Complementary analgesia may be beneficial as an adjunctive therapy.
      This pilot study presented eight patients with two odour therapies, lavender and
      lemon, two music therapies, relaxing and preferred music and a control condition,
      during vascular wound dressing changes. Although the therapies did not reduce the
      pain intensity during the dressing change there was a significant reduction in
      pain intensity for the lavender therapy and a reduction in pain intensity for the
      relaxing music therapy after the dressing change. This supports the use of these
      complementary therapies, which are inexpensive, easy to administer and have no
      known side effects, as adjunctive analgesia in this patient population. Earlier
      administration before dressing change may enhance these effects. Further research
      is required to ascertain why certain complementary therapies are more effective
      than others at relieving pain.

PMID- 15573018
TI  - Environmental Stress and the Brain's Reaction.

PMID- 15573019
TI  - Glutamate-hypothalamic-pituitary-adrenal axis interactions: implications for mood
      and anxiety disorders.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a pathologic
      feature of certain mood and anxiety disorders that results in the increased
      production and secretion of corticotropin-releasing factor. There is increasing
      preclinical evidence that glutamate, an excitatory amino acid, plays an important
      role in the regulation of the HPA axis. Activation of glutamatergic projections
      to limbic structures such as the amygdala and brainstem structures such as the
      nucleus tractus solitarius is implicated in the stress response. There are
      laboratory and clinical suggestions that glutamatergic N-methyl-D-aspartate
      (NMDA) receptor antagonists function as antidepressants, and that chronic
      antidepressant treatments have a significant impact on NMDA receptor function.
      Clinical investigations of glutamate antagonists in patients with mood and
      anxiety disorders are in their infancy, with a few reports suggesting the
      presence of mood-elevating properties. Ultimately, HPA axis modulators, serotonin
      enhancing agents, and glutamate antagonists might serve to increase neurotropic
      factors in key brain regions for affective and anxiety regulation, providing a
      putative final common pathway.

PMID- 15573020
TI  - Protein kinase a in major depression: the link between hypothalamic-pituitary
      adrenal axis hyperactivity and neurogenesis.
AB  - The latest and most generative biological theories of major depression center on
      two major hypotheses. The first focuses on the concept that hyperactivity of the
      hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological
      changes in the brain that accompany major depression. The second posits that
      neurogenesis leads to the repair of depression-related injuries. These two
      hypotheses are complementary: the former alludes to the etiology or consequences
      of depression, while the latter suggests mechanisms of antidepressant action.
      Significant crosstalk occurs between these two systems at many levels. Protein
      kinase A (PKA) may play an important role in this crosstalk at the intracellular
      level of signaling cascades. PKA is involved in the formation of long-term
      potentiation and fear conditioning in response to stress. Chronic stress leads to
      the suppression of hippocampal activity, which may cause the hyperactivity of the
      HPA axis during melancholic depression. PKA is also involved in the stimulation
      of hippocampal neurogenesis after antidepressant treatment. In theory,
      neurogenesis may lead to the restoration of hippocampal function, and this may be
      the mechanism that leads to antidepressant-mediated normalization of HPA
      hyperactivity. Thus, PKA is active during processes that potentially lead to
      depression and other processes that lead to the resolution of the illness. These
      opposing processes may be mediated by separate PKA isozymes that activate two
      distinct pathways. This review highlights the dual role of this enzyme in two
      biological hypotheses pertaining to depression and its treatment.

PMID- 15573021
TI  - Stress, peer affiliation, and transforming growth factor-beta1 in differentially
      reared primates.
AB  - A bidirectional regulatory interaction between the central nervous system and the
      immune system is largely provided by cytokines and their specific receptors,
      which are expressed by cells of both systems. Transforming growth factor-beta1
      (TGF-beta1), produced by glial cells and lymphocytes and regulated by steroid
      hormones, is one such cytokine. In the current study, we examined the
      relationship between TGF-beta1 and peer affiliation in bonnet macaques (Macaca
      radiata) either reared normally or exposed as infants to conditions in which
      their mothers faced fluctuating requirements for food procurement (variable
      foraging demand [VFD]). Rearing under VFD conditions has been previously shown to
      produce dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in these
      animals. Serum levels of TGF-beta1 after exposure to a moderate stressor had no
      correlation with peer affiliation under baseline conditions (r=.07), but were
      highly correlated with affiliation after subsequent challenge with a fear
      stimulus (r=.62). Affiliation after the fear stimulus also was inversely
      correlated with baseline levels of affiliation (r=-.71). These data suggest that
      changes in peripheral TGF-beta1 may be reflective of latent behavioral and
      biochemical propensities possibly related to affect. Further examination of the
      effects of early adversity will improve our understanding of the relationship
      between the HPA axis and immune function.

PMID- 15573022
TI  - CRHR1 antagonists as novel treatment strategies.
AB  - Research has provided considerable evidence for the hypothesis that corticotropin
      releasing hormone (CRH), the key central coordinator of stress-hormone
      homeostasis, also plays a role in the development and course of depression and
      anxiety disorders. Studies using animal models of anxiety, as well as mouse
      mutants, in which the gene coding for the CRH type 1 receptor (CRHR1) was
      genetically deleted supported the notion that enhanced CRH/CRHR1 signaling
      underlies depression and anxiety disorders. Therefore, a number of small
      nonpeptide molecules that antagonize CRHR1 have been developed. In animal models,
      these molecules had anxiolytic and other stress-alleviating effects. An initial
      clinical study showed that CRHR1 antagonism has beneficial effects on depression
      and anxiety symptoms at doses unharmful to neuroendocrine stress responsivity.

PMID- 15573023
TI  - Novel perspectives of central CRF/HPA axis dysfunction across a spectrum of
      clinical conditions and experimental primate models.

PMID- 15573024
TI  - Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of
      obesity.
AB  - Obesity has negative health consequences related to fat distribution,
      particularly the central or visceral accumulation of fat. The major complications
      associated with visceral obesity, termed the "Metabolic Syndrome of Obesity," or
      "Syndrome X," are type II diabetes, hypertension, and dyslipidemia. As with
      certain mood disorders, the syndrome may be a consequence of neuroendocrine
      perturbations typically associated with chronic stress. Our work with bonnet
      macaque monkeys provides an animal model for the relationship between early
      stress, behavioral and hypothalamic-pituitary-adrenal (HPA) axis dysregulation,
      and Syndrome X. During their infant's first half-year, mothers face a variable
      foraging demand (VFD), in which ample food varies unpredictably in the difficulty
      of its acquisition, and the offspring show persistent abnormalities in systems
      known to modulate stress and affective regulation. Early work on the bonnet
      macaque noted the emergence of a sample of spontaneously obese subjects as they
      matured. Using the VFD model, the current study showed that there was a clear
      relationship between early cerebrospinal fluid corticotropin-releasing factor
      levels and subsequently measured body mass index, supporting the hypotheses
      regarding the interactive roles of early experience and HPA axis dysregulation in
      the ontogeny of both metabolic and mood disorders.

PMID- 15573025
TI  - Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman
      primate hypothalamic-pituitary-adrenal axis and noradrenergic function.
AB  - The search for novel anxiolytics and antidepressants has focused on compounds
      with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis
      activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within
      the central nervous system, conceivably plays an important role in activating the
      neural sites involved in stress modulation. Deactivation of the HPA axis by
      glutamatergic neurotransmission modulation may represent a novel therapeutic
      approach. Accordingly, the acute intravenous effects of the novel metabotropic
      (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata)
      undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent
      measures were the magnitude of the increase of plasma cortisol and plasma 3
      methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the
      effects of 6 weeks of chronic oral administration of LY354740 on baseline
      (postcapture) plasma cortisol and MHPG levels in comparison to the identical
      measure in untreated controls were assessed. Subjects chronically treated with
      LY354740 received yohimbine infusions which were compared to yohimbine infusions
      and saline infusions in non-LY354740-treated subjects. Preliminary evidence
      supports the view that acute LY354740 infusion resulted in a marked diminution of
      yohimbine-induced stress response, as manifest by a substantial attenuation of
      cortisol and MHPG response observed in comparison to the saline-treated yohimbine
      condition. Chronic oral administration of LY354740 led to postcapture baseline
      cortisol levels which were markedly reduced (approximately 50 percent) in
      comparison to untreated control subjects; however, there were no significant
      parallel differences in MHPG levels. Yohimbine infusions elicited an increase in
      cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated
      subjects, in comparison to declines in cortisol values observed following vehicle
      infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects
      failed to achieve cortisol levels comparable in range to those of untreated
      subjects primarily because of their low baseline cortisol levels. In contrast,
      despite equivalent baselines, yohimbine-induced MHPG values were increased
      overall in the chronically treated group compared to the saline and yohimbine
      alone groups. Thus, LY354740 markedly reduced the acute corticoid and
      noradrenergic response elicited by yohimbine infusion. Chronic administration of
      LY354740 appears to present a safe and effective mechanism to markedly down
      modulate the HPA axis while retaining noradrenergic responsivity.

PMID- 15573026
TI  - Trends in motorcycle fatalities associated with alcohol-impaired driving--United
      States, 1983-2003.
AB  - Motorcycles are the most dangerous type of motor vehicle to drive. These vehicles
      are involved in fatal crashes at a rate of 35.0 per 100 million miles of travel,
      compared with a rate of 1.7 per 100 million miles of travel for passenger cars.
      The National Highway Traffic Safety Administration (NHTSA) has reported
      increasing numbers of motorcycle deaths associated with alcohol-impaired driving
      in recent years, especially among persons aged > or =40 years. To determine
      trends by age group in motorcycle fatalities overall and in those involving
      alcohol impairment, CDC analyzed data from the NHTSA Fatality Analysis Reporting
      System (FARS) for 1983, 1993, and 2003. This report summarizes the results of
      that analysis, which indicated that, during 1983-2003, the overall prevalence of
      elevated blood alcohol concentrations (BACs) among motorcycle drivers who died in
      crashes declined; however, the peak rate of death among alcohol-impaired
      motorcycle drivers shifted from those aged 20-24 years to those aged 40-44 years.
      Strong enforcement of existing BAC laws, together with other public health
      interventions aimed at motorcyclists, might reduce the crash mortality rate,
      especially among older drivers.

PMID- 15573027
TI  - Diagnoses of HIV/AIDS--32 States, 2000-2003.
AB  - An estimated 850,000-950,000 persons in the United States are living with human
      immunodeficiency virus (HIV), including 180,000-280,000 who do not know they are
      infected. To examine trends of diagnoses for 2000-2003, CDC analyzed HIV and
      acquired immunodeficiency syndrome (AIDS) together as HIV/AIDS (i.e., HIV
      infection with or without AIDS), counted by the year of earliest reported
      diagnosis of HIV infection. From 2000 to 2003, in 32 states that used
      confidential, name-based reporting of HIV and AIDS cases for > or =4 years, the
      overall annual rate of diagnosis of HIV/AIDS remained stable. However, rates
      among non-Hispanic black females were 19 times higher than rates among non
      Hispanic white females, underscoring the need for continued emphasis on programs
      targeting females in racial/ethnic minority populations to reduce the number of
      cases of HIV/AIDS.

PMID- 15573028
TI  - Number of persons tested for HIV--United States, 2002.
AB  - Strategies for preventing infection with human immunodeficiency virus (HIV)
      emphasize testing to identify infected persons and ensure access to appropriate
      medical care, treatment, and prevention services. To determine the number of
      persons who were tested for HIV during the preceding 12 months, CDC analyzed data
      from both the 2002 National Health Interview Survey (NHIS) and the 2002
      Behavioral Risk Factor Surveillance System (BRFSS) survey. This report summarizes
      the results of these analyses, which indicated that, in 2002, approximately 10%
      12% of persons aged 18-64 years in the United States reported being tested for
      HIV during the preceding 12 months, an estimated 16-22 million persons. Continued
      measurement of HIV testing by health surveys such as BRFSS and NHIS can be used
      in combination with program data and other surveys of populations at high risk to
      determine the impact of HIV strategies on increasing testing.

PMID- 15573029
TI  - Acute flaccid paralysis surveillance systems for expansion to other diseases,
      2003-2004.
AB  - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, the
      number of countries where polio is endemic has decreased from 125 in 1988 to six
      at the end of 2003. As part of the eradication strategy, a global surveillance
      system was established to 1) identify acute flaccid paralysis (AFP) cases in
      children aged < or =15 years and 2) deploy a network of accredited laboratories
      to perform virologic testing of stool specimens to determine whether the
      paralysis resulted from poliovirus infection. As AFP surveillance systems
      matured, countries increasingly applied AFP surveillance strategies and
      infrastructure to detect other diseases. This report describes the status of
      global AFP surveillance, including its expansion or use as a model in 131 (66%)
      of 198 countries for the reporting of measles and other vaccine-preventable
      diseases. As poliomyelitis is eradicated, AFP surveillance systems in these and
      other countries might be further expanded and adapted to improve the detection of
      and response to other diseases.

PMID- 15573030
TI  - Is the initial diagnostic impression of "noncardiac chest pain" adequate to
      exclude cardiac disease?
AB  - STUDY OBJECTIVE: In patients presenting to the emergency department (ED) with an
      initial diagnostic impression of noncardiac chest pain, we determine the 30-day
      incidence of adverse cardiac events and characteristics associated with those
      events. METHODS: The multicenter, prospectively collected Internet Tracking
      Registry for Acute Coronary Syndromes (i*tr ACS ) registry of patients with chest
      pain enrolled from June 1, 1999, to August 1, 2001, was reviewed. We included
      patients if the physician's initial diagnostic impression was noncardiac chest
      pain after the medical history, physical examination, and initial 12-lead ECG. ED
      records, inpatient records, and follow-up results were reviewed for evidence of
      an adverse cardiac event defined as ST-segment or non-ST-segment elevation
      myocardial infarction, unstable angina, revascularization, or cardiac death
      within 30 days. RESULTS: Of 17,737 patients enrolled in i*tr ACS , 2,992 had an
      initial emergency physician impression of noncardiac chest pain. Of these, 85
      (2.8%) patients had definite evidence for an adverse cardiac event. The adverse
      cardiac event group was older (61.2 versus 47.9 years), more likely to be men
      (58.6% versus 38.7%), and had a higher Acute Cardiac Ischemia-Time Insensitive
      Predictive Instrument score (26.1 versus 15.6). Factors associated with adverse
      cardiac events included hypercholesterolemia, diabetes, history of coronary
      artery disease, and history of congestive heart failure. CONCLUSION: When the
      initial impression is noncardiac chest pain, high-risk features such as
      traditional cardiovascular risk factors or a history of coronary artery disease
      are associated with adverse cardiac events. In the absence of well-defined
      criteria, treating physicians should consider further evaluation before
      diagnosing patients with noncardiac chest pain if these features are present.

PMID- 15573031
TI  - Chest pain in the emergency department: in search of the Holy Grail.

PMID- 15573032
TI  - Emergency department crowding and thrombolysis delays in acute myocardial
      infarction.
AB  - STUDY OBJECTIVE: We estimate the effect of emergency department (ED) crowding on
      door-to-needle time for patients given intravenous thrombolysis for suspected
      acute myocardial infarction. METHODS: This was a retrospective observational
      study of patients thrombolyzed in the ED for suspected acute myocardial
      infarction in 1998 to 2000 in 25 community and teaching hospital EDs in Ontario.
      EDs located close together and sharing a common ambulance diversion system were
      grouped into networks consisting of 2 to 5 hospitals each. At patient
      registration in an ED, the ambulance diversion status of all EDs in the network
      was determined. Network crowding was calculated as the percentage of EDs that
      were diverting ambulances on patient registration, categorized as none (0%),
      moderate (<60%), and high (> or =60%). Door-to-needle time was defined as time
      from ED registration to drug administration. Multivariable quantile regression
      and logistic regression were carried out; covariates included age, sex, ECG
      characteristics, previous acute myocardial infarction, vital signs, time of
      presentation, and hospital type. RESULTS: A total of 3,452 thrombolysis patients
      were included: mean age was 62.9 years, and 73% were male patients. Overall
      median door-to-needle time was 43 minutes (interquartile ratio 27 to 80). Median
      door-to-needle time was 40, 45, and 47 minutes in conditions of none, moderate,
      and high network crowding, respectively ( P <.001). The adjusted odds ratios for
      door-to-needle time delay (>30 minutes) and major delay (>60 minutes) were 1.32
      (95% confidence interval [CI] 0.98 to 1.79) and 1.40 (95% CI 1.12 to 1.75),
      respectively, for high network crowding compared with none, and 1.21 (95% CI 0.89
      to 1.63) and 1.06 (95% CI 0.86 to 1.29), respectively, for moderate crowding
      compared with none. In multivariate analyses, moderate and high crowding
      conditions were associated with increased median door-to-needle time (3.0 minutes
      [95% CI 0.1 to 6.0] and 5.8 minutes [95% CI 2.7 to 9.0], respectively).
      CONCLUSION: ED crowding is associated with increased door-to-needle times for
      patients with suspected acute myocardial infarction and may represent a barrier
      to improving cardiac care in EDs.

PMID- 15573033
TI  - The quality gap: searching for the consequences of emergency department crowding.

PMID- 15573034
TI  - Standardized reporting guidelines for studies evaluating risk stratification of
      emergency department patients with potential acute coronary syndromes.

PMID- 15573035
TI  - Pressure immobilization delays mortality and increases intracompartmental
      pressure after artificial intramuscular rattlesnake envenomation in a porcine
      model.
AB  - STUDY OBJECTIVES: We determine the effect of pressure immobilization on mortality
      and intracompartmental pressure after artificial intramuscular Crotalus atrox
      envenomation in a porcine model. METHODS: We prospectively studied 20 pigs using
      a randomized, controlled design. After anesthesia, C atrox venom (20 mg/kg) was
      injected with a 22-gauge needle 10 mm deep into the tibialis anterior muscle of
      the hind leg. Pigs were randomized to receive either pressure immobilization
      (applied 1 minute after envenomation and maintained throughout the duration of
      the experiment) or no pressure immobilization. We measured time to death,
      intracompartmental pressure before venom injection and at 2 hours after
      injection, and leg circumference at a standardized location before injection and
      immediately postmortem. Duration of survival was compared using Kaplan-Meier
      survival analysis. RESULTS: The dose of venom resulted in 100% mortality. The
      median survival was longer in the pressure immobilization group (191 minutes,
      range 140 to 240 minutes) than in the control group (median 155 minutes, range
      119 to 187 minutes). The difference between the groups was 36 minutes (95%
      confidence interval [CI] 2 to 64 minutes; P =.0122). The mean intracompartmental
      pressures were 67+/-13 mm Hg+/-SD with pressure immobilization and 24+/-5 mm Hg
      without pressure immobilization. The difference between groups was 43 mm Hg (95%
      CI 32 to 53 mm Hg). The mean circumferences were 14.3 cm in the pressure
      immobilization group and 19.1 cm in the control group. The difference between
      groups was -4.8 cm (95% CI -5.7 to -3.9 cm). CONCLUSION: Compared with control
      animals without treatment, the pressure immobilization group had longer survival,
      less swelling, and higher intracompartmental pressures after artificial,
      intramuscular C atrox envenomation in our porcine model.

PMID- 15573036
TI  - Do hobo spider bites cause dermonecrotic injuries?

PMID- 15573037
TI  - Loxoscelism: old obstacles, new directions.
AB  - Loxosceles spiders have a worldwide distribution and are considered one of the
      most medically important groups of spiders. Envenomation (loxoscelism) can result
      in dermonecrosis and, less commonly, a systemic illness that can be fatal. The
      mechanism of venom action is multifactorial and incompletely understood. The
      characteristic dermonecrotic lesion results from the direct effects of the venom
      on the cellular and basal membrane components, as well as the extracellular
      matrix. The initial interaction between the venom and tissues causes complement
      activation, migration of polymorphic neutrophils, liberation of proteolytic
      enzymes, cytokine and chemokine release, platelet aggregation, and blood flow
      alterations that result in edema and ischemia, with development of necrosis.
      There is no definitive treatment for loxoscelism. However, animal model studies
      suggest the potential value of specific antivenom to decrease lesion size and
      limit systemic illness even when such administration is delayed.

PMID- 15573038
TI  - Oral arsenic trioxide poisoning and secondary hazard from gastric content.
AB  - In a suicide attempt, a 54-year-old man ingested arsenic trioxide. Gastric lavage
      was performed, but most of the poison remained as a mass in his stomach. A total
      gastrectomy was also performed to avoid intestinal perforation and arsenic
      poisoning. After the operation, he developed ventricular fibrillation. At one
      point, his circulation recovered spontaneously, but he later died from refractory
      circulatory failure. Many medical staff members were exposed to fumes from the
      patient's stomach. Some of the staff were diagnosed with corneal erosion or
      laryngitis. Because arsenic trioxide reacts with acid to produce arsine, the
      symptoms experienced by medical staff are directly attributable to arsine
      produced as a result of the reaction of arsenic trioxide with gastric acid. This
      case highlights the need for the introduction of protective measures to safeguard
      medical staff from exposure to arsine gas during the treatment of patients
      poisoned from ingested arsenic trioxide.

PMID- 15573039
TI  - Use of a portable forced air system to convert existing hospital space into a
      mass casualty isolation area.
AB  - STUDY OBJECTIVE: Patients with communicable diseases may require respiratory
      isolation to reduce the chance of transmission to health care workers and the
      public. This project was conducted to determine whether negative-pressure
      isolation for multiple patients can be achieved quickly and effectively using
      general hospital space not previously dedicated to respiratory isolation.
      METHODS: The physical therapy gymnasium was the area designated to test the
      ability to create a negative-pressure isolation environment in a large space. The
      conversion was planned in advance of an unscheduled drill to convert the space.
      Four high-efficiency particulate air (HEPA) filtered forced air machines were
      used to generate negative pressure. The units were vented to the outside air by a
      25-foot length of 10-inch-diameter reusable duct. We evaluated the time needed
      for equipment setup and room conversion and noted any subjective difficulty with
      either setup or operation of the equipment. We measured the ability of the
      equipment to generate a negative air pressure relative to adjacent areas and
      determined the noise levels created during the use of different combinations of
      machines at various power settings. RESULTS: After drill activation and the
      request for equipment setup, 1 hour was required to convert the physical therapy
      gymnasium into an operational negative-pressure environment. The room pressure
      readings "high" power ranged from -1.5 to -13 Pa (-0.006 to -0.052 inches of
      water), and noise levels ranged from 70 to 76 dB. Calculated air changes per hour
      using 1, 2, 3, or 4 units running simultaneously at "high" power were 4.1, 8.2,
      12.3, and 16.4, respectively. Using 4 units at once running at "low" power
      setting yielded 8.2 air changes per hour and generated a room pressure reading of
      -8.0 Pa, or -0.032 inches of water. CONCLUSION: Portable HEPA filtered forced air
      units are an effective means of creating large patient care areas with the
      negative-pressure environment required for respiratory isolation. This design
      results in a significantly lower-cost alternative compared with construction of
      individual rooms or units with similar capability and can be retrofitted to
      existing space. This type of unit would allow treatment of many more patients
      than current hospital capability would permit and would be an important asset in
      meeting the needs created by bioterrorism or a naturally occurring epidemic.

PMID- 15573040
TI  - An evaluation of portable high-efficiency particulate air filtration for
      expedient patient isolation in epidemic and emergency response.
AB  - Extraordinary incidents resulting in airborne infectious disease outbreaks could
      produce patient isolation requirements that exceed most hospitals' capacity. This
      article investigates expedient methods to establish airborne infection isolation
      areas using a commercially available portable filtration unit and common hardware
      supplies. The study was conducted within a conventional, nonisolation hospital
      room, and researchers evaluated several airborne isolation configurations that
      did not require building ventilation or structural modifications. A portable high
      efficiency particulate air filtration unit and full-length plastic curtains
      established a "zone-within-zone" protective environment using local capture and
      directional airflows. The cost of constructing the expedient configurations was
      less than US2,300 dollars and required fewer than 3 person-hours to construct. A
      medical nebulizer aerosolized polystyrene latex microspheres to generate
      respirable condensation nuclei. Aerosol spectrometers sized and counted
      respirable particles at the source patient and health care worker positions and
      in areas outside the inner zone. The best-performing designs showed no measurable
      source migration out of the inner isolation zone and mean respirable particle
      counts up to 87% lower at the health care worker position(s) than those observed
      directly near the source patient location. Investigators conclude that with
      careful implementation under emergency circumstances in which engineered
      isolation rooms are unavailable, expedient methods can provide affordable and
      effective patient isolation while reducing exposure risks and potential disease
      transmission to health care workers, other patients, and visitors.

PMID- 15573041
TI  - Previous emergency department use among homicide victims and offenders: a case
      control study.
AB  - STUDY OBJECTIVE: We differentiate risk factors for future homicide victimization
      and offending, and we measure emergency department (ED) use among homicide
      victims, offenders, and controls. METHODS: The design was a matched case-control
      study conducted in Bernalillo County, NM, and its university-affiliated health
      sciences center and hospital. All Bernalillo County homicide victims (N=124) and
      offenders (N=138) identified between January 1996 and December 2001 who were
      linked to university physician billing records and who had health care use during
      the 3 years before the homicide incident were included as cases. Randomly
      selected age-matched (+/-1 year) and sex-matched subjects with health care use
      within 3 years of their matched pair's homicide were included as controls. Main
      outcome measures were the number and type of ED visits by cases and controls.
      RESULTS: Among the 124 victims and 138 offenders who used health care, most were
      men (80%) and averaged 27.7 years of age. Victims and offenders had similar
      health care use and were grouped for final analyses. Cases (victims and
      offenders) were more likely to have had an ED visit within 3 years of the
      homicide (85%) compared with controls (59%) (odds ratio [OR] 4.3; 95% confidence
      interval [CI] 3.0 to 6.2). Within previous ED visits, assault (OR 4.5; 95% CI 2.9
      to 7.0), firearm injury (OR 13.6; 95% CI 4.9 to 37.7), and substance abuse (OR
      3.7; 95% CI 2.2 to 6.0) were associated with future homicide. ED visits clustered
      closer to the homicide incident for cases (median days before the homicide -402
      days; 95% CI -434 to -364) compared with controls (median -487 days; 95% CI -498
      to -474). CONCLUSION: Patients with ED visits for assault, firearm injuries, and
      substance abuse are at increased risk for homicide and often have an escalating
      number of visits leading up to the homicide event. ED-based identification and
      referral programs similar to those used for intimate partner violence or other
      preventive strategies should be considered for this high-risk population.

PMID- 15573042
TI  - National Highway Traffic Safety Administration (NHTSA) notes. Analysis of crashes
      involving 15-passenger vans.

PMID- 15573044
TI  - The loading dock.

PMID- 15573045
TI  - Christmas Eve in the department.

PMID- 15573046
TI  - Images in emergency medicine. Diaphragmatic rupture.

PMID- 15573047
TI  - Needlestick/sharps injuries among vocational school nursing students in southern
      Taiwan.
AB  - BACKGROUND: Although most needlestick/sharps injuries (NSIs/SIs) research focuses
      on health care workers (HCWs), students in hospital internships are also at risk.
      Investigations that examined NSIsS/SIs in student populations generally studied
      medical rather than nursing students (NSs). In 1999, approximately 17,000
      Taiwanese nursing graduates were exposed to the hazard of NSIs/SIs. We examined
      the frequency and mechanism of NSIs/SIs among vocational school NSs in southern
      Taiwan. METHODS: Between July and December of 1999, within 1 week after the NSs
      completed their internship training, one of the researchers, who was a teacher in
      this vocational school, asked them to fill out questionnaires. RESULTS: Five
      hundred twenty-seven of 550 (92.6%) questionnaires were considered valid. Two
      hundred sixty-four of 527 (50.1%) responders sustained one or more NSIs/SIs.
      Ninety-six of 527 (18.2%) responders suffered contaminated NSIs/SIs. The average
      number of NSIs/SIs per student was 8.0 times/year (4.9 times/student/year for
      NSIs and 3.1 times/student/year for SIs). NSIs/SIs rates for NSs in 10-week and 4
      week internships were significantly different ( P = .039): 53.3% versus 43.7%,
      respectively. The NSIs/SIs frequencies were influenced by length of internship:
      7.3 times/student/year in 10-week internship and 11.7 times/student/year in 4
      week internship. Logistic regression analysis indicated that length of internship
      rotation was statistically significant with respect to contaminated NSIs/SIs (OR
      = 1.682; 95% CI: 1.005-2.81; P = .048). CONCLUSIONS: The NSIs/SIs frequencies of
      NSs were higher than those for HCWs. We found that frequency of NSIs/SIs for
      vocational school NSs is above average. Whether the young age of these NSs put
      them at greater risk for NSIs/SIs warrants further inquiry.

PMID- 15573048
TI  - Prediction rules to identify patients with methicillin-resistant Staphylococcus
      aureus and vancomycin-resistant enterococci upon hospital admission.
AB  - BACKGROUND: In 2003, the Society of Healthcare Epidemiology of America (SHEA)
      recommended surveillance cultures upon hospital admission for patients at high
      risk for carriage of vancomycin-resistant enterococci (VRE) and methicillin
      resistant Staphylococcus aureus (MRSA). The aim of this study was to assess the
      validity of factors from past medical history in defining patients at high risk
      for subsequent positive cultures with VRE or MRSA upon hospital admission.
      METHODS: Subjects were adult inpatients admitted to nonintensive care wards of
      the index hospital during 2001-2002. Cases had MRSA or VRE positive clinical
      cultures within 48 hours of hospital admission. Patients with previous history of
      MRSA or VRE were excluded. RESULTS: Nineteen thousand three hundred ninety-nine
      patients were included, with 273 cases of VRE or MRSA. Previous admission within
      1 year of current admission had a sensitivity of 56.8% and a specificity of 88.4%
      for predicting a case of MRSA or VRE. Individually, the sensitivity and
      specificity for admission within the past year were 50.5% and 88.4%,
      respectively, for MRSA and 76.9% and 88.4%, respectively, for VRE. CONCLUSIONS:
      Patients with a previous hospital admission represent a high-risk population for
      positive culture for VRE and MRSA and may be a group of which active surveillance
      is indicated.

PMID- 15573049
TI  - Impact of safety devices for preventing percutaneous injuries related to
      phlebotomy procedures in health care workers.
AB  - BACKGROUND: Use of protective devices has become a common intervention to
      decrease sharps injuries in the hospitals; however few studies have examined the
      results of implementation of the different protective devices available.
      OBJECTIVE: To determine the effectiveness of 2 protective devices in preventing
      needlestick injuries to health care workers. METHODS: Sharps injury data were
      collected over a 7-year period (1993-1999) in a 3600-bed tertiary care university
      hospital in France. Pre- and postinterventional rates were compared after the
      implementation of 2 safety devices for preventing percutaneous injuries (PIs)
      related to phlebotomy procedures. RESULTS: From 1993 to 1999, an overall decrease
      in the needlestick-related injuries was noted. Since 1996, the incidence of
      phlebotomy-related PIs has significantly decreased. Phlebotomy procedures
      accounted for 19.4% of all percutaneous injuries in the preintervention period
      and 12% in the postintervention period (RR, O.62; 95% CI, 0.51-0.72; P < .001).
      Needlestick-related injuries incidence rate decreased significantly after the
      implementation of the 2 safety devices, representing a 48% decline in incidence
      rate overall. CONCLUSIONS: The implementation of these safety devices apparently
      contributed to a significant decrease in the percutaneous injuries related to
      phlebotomy procedures, but they constitute only part of a strategy that includes
      education of health care workers and collection of appropriate data that allow
      analysis of residuals percutaneous injuries.

PMID- 15573050
TI  - Effect of silver-coated urinary catheters: efficacy, cost-effectiveness, and
      antimicrobial resistance.
AB  - BACKGROUND: Urinary tract infections (UTIs) are the most common nosocomial
      infection experienced by patients in United States hospitals and are responsible
      for significant morbidity and excess hospital costs. The purpose of this study
      was to determine the efficacy of a silver alloy, hydrogel-coated, urinary
      catheter in the prevention of catheter-associated UTI, to assess the cost
      effectiveness of the coated catheter, and to test for the emergence of silver
      resistance in urinary microbial isolates. METHODS: A 2-year prospective
      surveillance study in 10 patient care units was conducted to determine the rate
      of catheter-associated UTI. Historic control data was utilized to assess the
      effect of the coated catheter. A cost-effectiveness analysis was conducted using
      a range of cost estimates. Silver susceptibility was determined for microbes
      responsible for catheter-associated UTI. RESULTS: Data were analyzed using a
      Poisson regression model. The rate of catheter-associated UTI fell from 6.13/1000
      catheter-days during the period 1999-2000 to 2.62/1000 catheter-days during 2001
      2002 ( P = .002). Calculated cost savings varied widely. Modest savings were
      achieved at the realistic lower cost estimates. No silver-resistant microbes were
      recovered in the susceptibility tests. CONCLUSIONS: The introduction of a silver
      alloy, hydrogel-coated urinary catheter was associated with a significant decline
      in nosocomial UTI and cost savings over the range of cost estimates. Silver
      resistant urinary pathogens were not recovered from patients experiencing
      catheter-associated UTI during the study period.

PMID- 15573051
TI  - Impact of implementing a method of feedback and accountability related to contact
      precautions compliance.
AB  - BACKGROUND: In January 2002, Infection control professionals for Spartanburg
      Regional Healthcare System held a planning retreat focused on patient safety. The
      main challenge discussed was the control of antibiotic-resistant organisms.
      Rounds on the patient care units had revealed compliance issues with the current
      isolation procedures. The team developed a process improvement project coined the
      Effective Processes in Infection Control Project (EPIC). With a broad challenge
      of antibiotic resistance, the focus was narrowed to isolation precautions for
      methicillin-resistant Staphylococcus aureus (MRSA). METHODS: The initial stage of
      the EPIC project was education, followed by routine unit rounds to monitor
      compliance. A tool was developed to provide immediate feedback for the nursing
      units. Summary reports were generated for clinical directors as a method of
      accountability for unit leadership. Rates for facility-acquired MRSA were
      monitored and compared with MRSA days at risk. RESULTS: Over a 1-year period of
      increased accountability, the facility-acquired rate of MRSA decreased by 30%,
      even though the days at risk increased. The decrease was maintained during year
      2. CONCLUSIONS: The results of this project point to the importance of
      accountability with isolation precautions in the effort to combat the spread of
      MRSA in the hospital setting.

PMID- 15573052
TI  - Factors influencing health care workers' adherence to work site tuberculosis
      screening and treatment policies.
AB  - BACKGROUND: Despite the known risk of tuberculosis (TB) to health care workers
      (HCWs), research suggests that many are not fully adherent with local TB
      infection control policies. The objective of this exploratory study was to
      identify factors influencing HCWs' adherence to policies for routine tuberculin
      skin tests (TSTs) and treatment of latent TB infection (LTBI). METHODS: Sixteen
      focus groups were conducted with clinical and nonclinical staff at 2 hospitals
      and 2 health departments. Participants were segmented by adherence to TST or LTBI
      treatment policies. In-depth, qualitative analysis was conducted to identify
      facilitators and barriers to adherence. RESULTS: Among all focus groups, common
      themes included the perception that the TST was mandatory, the belief that
      conducting TSTs at the work site facilitated adherence, and a general
      misunderstanding about TB epidemiology and pathogenesis. Adherent groups more
      commonly mentioned facilitators, such as the perception that periodic tuberculin
      skin testing was protective and the employee health (EH) provision of support
      services. Barriers, such as the logistic difficulty in obtaining the TST, the
      perception that LTBI treatment was harmful, and a distrust of EH, emerged
      consistently in nonadherent groups. CONCLUSIONS: This information may be used to
      develop more effective interventions for promoting HCW adherence to TB prevention
      policies. Informed efforts can be implemented in coordination with reevaluations
      of infection control and EH programs that may be prompted by the publication of
      the revised TB infection control guidelines issued by the Centers for Disease
      Control and Prevention in 2005.

PMID- 15573053
TI  - Impact of a formulary switch from ticarcillin-clavulanate to piperacillin
      tazobactam on colonization with vancomycin-resistant enterococci.
AB  - BACKGROUND: The prevalence of vancomycin-resistant enterococci (VRE) is
      increasing, despite infection control measures. Limited data link ticarcillin
      clavulanate to higher VRE prevalence. METHODS: Active surveillance for VRE was
      conducted before and after a formulary switch from ticarcillin-clavulanate to
      piperacillin-tazobactam. Rectal swabs were obtained serially in 863 adult
      patients admitted to intensive care units (ICUs) between November 1, 2000 and
      September 30, 2004. RESULTS: In the postswitch period, 38 of 497 (7.6%) patients
      acquired VRE versus 42 of 366 (11.5%) patients in the preswitch period. Survival
      analysis showed an overall hazard ratio (HR) of .68 postswitch versus preswitch (
      P = .07), with the greatest change in the surgical ICU (HR = .17, P = .006).
      Multivariate analysis showed an overall HR = .51 ( P = .004). Hospital-wide,
      nonstool VRE clinical cultures fell from 39 (.58/1000 patient days) in the 10
      month preswitch period to 27 (.33/1000 patient days) in the 12-month postswitch
      period. Infection control practices and use of other antibiotics remained stable.
      CONCLUSIONS: VRE acquisition appeared to decrease in association with a formulary
      change from ticarcillin-clavulanate to piperacillin-tazobactam.

PMID- 15573054
TI  - National Nosocomial Infections Surveillance (NNIS) System Report, data summary
      from January 1992 through June 2004, issued October 2004.

PMID- 15573055
TI  - Susceptibility of coagulase-negative staphylococcal nosocomial bloodstream
      isolates to the chlorhexidine/silver sulfadiazine-impregnated central venous
      catheter.

PMID- 15573056
TI  - Private sector hospital response to the 2003 dengue outbreak in the Indian
      capital metropolis of Delhi.
AB  - During 2003, the Indian capital metropolis of Delhi was afflicted with an
      outbreak of dengue. A private-sector tertiary care hospital responded instantly
      to the sudden influx of 162 patients during an 8-week interval. That was an
      unusual challenge because, until 1997, the hospital had exclusively managed
      patients with ophthalmic disorders. Dengue patients received fiscal concessions
      and several free services. A multidisciplinary cell was commissioned for case
      management. Apart from a diagnosis of patients with dengue and their clinical
      management, suspected or confirmed dengue episodes were instantly reported to
      health authorities. Anti-mosquito measures in the hospital premises including
      residential areas for the nursing personnel prevented any local virus
      transmission. The integrated therapeutic and public health response was
      associated with a 1.23% case fatality rate. The protocol developed during the
      dengue outbreak would address every locally reportable disease in the future.

PMID- 15573057
TI  - Hepatitis B and hepatitis C virus prevalence among dialysis patients in Bahrain
      and Saudi Arabia: a survey by serologic and molecular methods.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were assessed
      among 81 Bahraini and 34 Saudi hemodialysis patients and 7714 Bahraini and 2330
      Saudi blood donors. Higher prevalence of HCV (9.24% vs 0.30%), hepatitis B
      surface antigen (5.88% vs 0.62%) were seen in patients versus control patients,
      and in Saudi patients compared with Bahraini patients. HCV genotypes were HCV
      1a/1b plus HCV 4 among Bahraini patients and HCV 2/2a plus HCV 4 among Saudi
      patients. This is the first report on viral hepatitis in Bahrain and the first to
      compare HBV/HCV among dialysis patients in the Eastern Arabian Peninsula.

PMID- 15573058
TI  - The state of the science of health care epidemiology, infection control, and
      patient safety, 2004.
AB  - Being aware and implementing the latest and best scientific evidence in infection
      control and health care epidemiology is critical to enhancing patient outcomes.
      In this review, the latest published scientific data in health care epidemiology
      and patient safety were reviewed for the period May 2003-May 2004. Medline
      reviews and reviews of infection control and infectious diseases journals were
      used for this period. The latest guidelines and publications on antimicrobial
      resistance, nursing or infection control professional staffing, West Nile virus,
      and Severe Acute Respiratory Syndrome (SARS) are included. Awareness of these and
      other important infection control publications is essential if the latest
      measures are to be implemented to prevent and control health care-associated
      infections.

PMID- 15573060
TI  - HICPAC/SHEA--conflicting guidelines: what is the standard of care?

PMID- 15573062
TI  - Monitoring surgical performance.

PMID- 15573063
TI  - Control chart methods for monitoring cardiac surgical performance and their
      interpretation.

PMID- 15573064
TI  - Monitoring clinical performance: a commentary.

PMID- 15573065
TI  - Monitoring cardiac surgical performance: a commentary.

PMID- 15573066
TI  - Supraventricular tachyarrhythmias in Ebstein anomaly: management and outcome.
AB  - OBJECTIVE: This study was undertaken to review the role of electrophysiology
      testing and to determine the early and late results of medical and surgical
      management of supraventricular tachyarrhythmias in Ebstein anomaly. METHODS: We
      reviewed 130 patients between 1990 and 2001 with Ebstein anomaly and history of
      tachyarrhythmia with a median age of 25 years (mean age 27.5 years); 106
      underwent electrophysiologic testing and 24 had documented atrial flutter or
      fibrillation. We excluded 21 patients: negative results of testing (n = 18),
      ventricular tachycardia (n = 2), and junctional tachycardia (n = 1). The
      remaining 109 patients had more than one mechanism: accessory pathway-mediated
      tachycardia (n = 49), atrioventricular nodal reentrant tachycardia (n = 10), and
      atrial flutter/fibrillation (n = 70). RESULTS: Eighty-three patients underwent at
      least one arrhythmia procedure combined with surgery for Ebstein anomaly. Early
      mortality was 4.8%. Forty-one patients underwent surgical ablation of an
      accessory pathway without recurrent accessory pathway-mediated tachycardia at a
      mean follow-up of 48 months. Seven patients underwent surgical perinodal
      cryoablation for atrioventricular nodal reentrant tachycardia without recurrence
      at a mean follow-up of 57 months. Forty-eight patients underwent surgical
      intervention for atrial flutter or fibrillation (right-sided maze procedure, n =
      38, and cryoablation of the atrial isthmus, n = 10). Freedom from recurrent
      atrial flutter or fibrillation was 75% at a mean follow-up of 34 months.
      CONCLUSION: Concomitant arrhythmia procedures can be performed without increase
      in early mortality and should be added to Ebstein repairs for all patients who
      have supraventricular tachyarrhythmias. Surgical procedures for accessory pathway
      mediated tachycardia and atrioventricular nodal reentrant tachycardia give
      excellent (100%) freedom from recurrence of those arrhythmias. Surgical
      intervention for atrial flutter/fibrillation yields freedom from late recurrence
      in 75% of cases.

PMID- 15573067
TI  - The Contegra conduit in the right ventricular outflow tract induces supravalvular
      stenosis.
AB  - OBJECTIVE: We sought to evaluate the incidence and nature of pulmonary stenosis
      after implantation of the bovine jugular vein graft (Contegra; Medtronic, Inc,
      Minneapolis, Minn) in the right ventricular outflow tract. METHODS: Between May
      2000 and September 2002, 58 Contegra conduits (8-22 mm) were implanted during
      primary (n = 27) or redo operations (n = 31) in 57 patients, with ages ranging
      from 2 days to 48 years (mean, 9 years). Indications were truncus arteriosus (n =
      16), tetralogy of Fallot (n = 28), pulmonary replacement in the Ross operation (n
      = 10), and Rastelli-type repair for double-outlet right ventricle (n = 4).
      Echocardiography was prospectively performed by a fixed team of investigators
      during follow-up (mean, 22.7 +/- 10 months). A peak gradient of greater than 50
      mm Hg was considered severe stenosis. RESULTS: Two patients died from
      Staphylococcus aureus -induced septicemia and enterococcal endocarditis after 12
      days and 12 weeks, respectively. One patient died of heart failure caused by
      endocardial fibroelastosis after 1 year. Freedom from severe stenosis at the
      distal anastomosis was 91% +/- 3% at 3 months, 68% +/- 6% at 12 months, and 49%
      +/- 8% at 24 months. The risk of development of stenosis does not change over
      time. Younger age and its derivatives (graft size and indication) are
      significantly related to the occurrence of severe stenosis ( P < .0001).
      Seventeen (29%) conduits required an endovascular intervention (balloon
      dilatation or stent). Seven (12%) conduits were explanted (endocarditis, 2;
      stenosis, 5). Histologic analysis of the explanted conduits showed excessive
      proliferation of neointima at the level of the distal anastomosis. Valve
      regurgitation was observed in 9 (16%) conduits and was always secondary to
      dilatation in the presence of severe distal stenosis. CONCLUSION: The Contegra
      conduit induces a neointimal proliferation at the level of the pulmonary
      anastomosis. This leads to a high incidence of severe stenosis at intermediate
      term follow-up.

PMID- 15573068
TI  - Preoperative cerebral blood flow is diminished in neonates with severe congenital
      heart defects.
AB  - OBJECTIVE: Impaired neurodevelopmental outcome represents a major morbidity for
      survivors of infant heart surgery for congenital heart defects. Previous studies
      in these neonates have reported preoperative microcephaly, periventricular
      leukomalacia, and other findings. The hypothesis of this study is that
      preoperative cerebral blood flow is substantially diminished and might relate to
      preoperative neurologic conditions. METHODS: Preoperative brain magnetic
      resonance imaging was performed. Cerebral blood flow measurements in infants with
      congenital heart defects were obtained by using a novel noninvasive magnetic
      resonance imaging technique, pulsed arterial spin-label perfusion magnetic
      resonance imaging. Cerebral blood flow was measured before the operation under
      standard ventilation and repeated after increased carbon dioxide. RESULTS: A
      total of 25 term infants were studied. The average age at the time of the
      operation was 4.4 +/- 4.6 days. Congenital heart defects varied widely.
      Microcephaly occurred in 24% (6/25). Baseline cerebral blood flow was 19.7 +/-
      9.2 mL . 100 g -1 . min -1 (8.0-42.2 mL . 100 g -1 . min -1 ). Five patients had
      cerebral blood flow measurements of less than 10 mL . 100 g -1 . min -1 . Mean
      hypercarbic cerebral blood flow increased to 40.1 +/- 20.3 mL . 100 g -1 . min -1
      (11.4-94.0 mL . 100 g -1 . min -1 , P < .001). Pairwise analyses found that low
      hemoglobin levels were associated with higher baseline cerebral blood flow values
      ( P = .04). Periventricular leukomalacia occurred in 28% (7/25) and was
      associated with decreased baseline cerebral blood flow values ( P = .05) and a
      smaller change in cerebral blood flow with hypercarbia ( P = .003). CONCLUSIONS:
      Structural brain abnormalities are common in these neonates before surgical
      intervention. Preoperative cerebral blood flow for this cohort was low and
      drastically reduced in some patients. Low cerebral blood flow values were
      associated with periventricular leukomalacia. Carbon dioxide reactivity was
      preserved but might be compromised by some aspects of the cardiac anatomy. The
      full spectrum of cerebral blood flow measurements with this technique in
      congenital heart defects and their long-term significance require continued
      investigation.

PMID- 15573069
TI  - Specific inhibition of p38 mitogen-activated protein kinase with FR167653
      attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension
      in rats.
AB  - OBJECTIVES: p38 mitogen-activated protein kinase is associated with many clinical
      entities characterized by inflammation. We postulated that inhibition of p38
      mitogen-activated protein kinase with FR167653 attenuates inflammation and the
      development of pulmonary hypertension in monocrotaline-treated rats. METHODS:
      Rats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2)
      the FR group (daily FR167653, 2 mg . kg(-1) . d(-1)), (3) the MCT group (daily
      0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the
      MCT+FR group (daily FR167653, 2 mg . kg(-1) . d(-1), the day after a single MCT
      dose). Body weight, pulmonary artery pressure, and morphometric changes of the
      pulmonary artery with the histopathologic method were observed weekly for 4
      weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory
      cytokine expression in the lung were measured. RESULTS: Four weeks after
      monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group
      was lower than in the MCT group (MCT+FR vs MCT: 24.7 +/- 1.9 vs 36.5 +/- 2.1 mm
      Hg; P < .05). In morphometric analysis the percentage of medial wall thickness
      and the percentage of muscularization in the MCT+FR group were reduced compared
      with those in the MCT group after 4 weeks (P < .05); however, the number of
      macrophages was not significantly different. p38 mitogen-activated protein kinase
      activity was significantly attenuated in the MCT+FR group compared with in the
      MCT group (7.2 +/- 0.52 vs 2.1 +/- 0.23 fold-increase, P < .05, at 1 week).
      Although mRNA levels of tumor necrosis factor alpha and interleukin 1beta were
      reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor
      alpha: 1.18 +/- 0.36 vs 3.05 +/- 1.12 fold-increase, P < .05, at 2 weeks;
      interleukin 1beta: 2.2 +/- 0.34 vs 4.4 +/- 1.09 fold-increase, P < .05, at 1
      week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA
      expression induced by monocrotaline (3.2 +/- 0.62 vs 3.1 +/- 0.42 fold-increase,
      at 1 week). CONCLUSION: FR167653 significantly attenuates the expression of
      inflammatory cytokines, ultimately preventing the progression of pulmonary
      hypertension. These results suggest that p38 mitogen-activated protein kinase
      might play a central role in the molecular events that underlie the development
      and progression of pulmonary hypertension.

PMID- 15573070
TI  - Cold blood cardioplegia versus cold crystalloid cardioplegia: a prospective
      randomized study of 1440 patients undergoing coronary artery bypass grafting.
AB  - OBJECTIVES: A large number of experimental studies have indicated that blood
      cardioplegia might be superior to crystalloid cardioplegia for myocardial
      protection during ischemic arrest. However, no prospectively randomized studies
      of large patient series have been undertaken to prove potential differences in
      clinical course. METHODS: Over a 52-month period, all patients undergoing on-pump
      coronary artery bypass operated on by 2 surgeons were prospectively randomized to
      receive either cold crystalloid cardioplegia (group C) or cold blood cardioplegia
      (group B) during aortic crossclamping. RESULTS: Altogether, 1440 patients aged 37
      to 89 years (median, 66 years) entered the study (group C, n = 719; group B, n =
      721). The groups were comparable in all major demographic, preoperative, and
      operative variables. The clinical course turned out to be nearly identical for
      both groups. No statistically significant differences were seen concerning
      spontaneous sinus rhythm after aortic declamping, use of inotropic drugs or intra
      aortic balloon pumping, postoperative ventilatory support, bleeding and rate of
      allogeneic blood transfusions, perioperative myocardial infarction, episodes of
      atrial fibrillation, stroke or minor neurologic dysfunction, renal function,
      infections, physical rehabilitation, or mortality. Also, in subgroups of patients
      at higher operative risk (female sex, age >70 years, unstable angina, diabetes,
      emergency operation, ejection fraction <0.50, crossclamping time >50 minutes, and
      EuroSCORE >4), no statistically significant differences could be demonstrated
      between the groups. CONCLUSIONS: There were no significant differences whether
      myocardial protection was performed with cold blood cardioplegia or cold
      crystalloid cardioplegia during aortic crossclamping in patients undergoing
      coronary artery bypass grafting. The extra costs related to blood cardioplegia
      might be saved.

PMID- 15573071
TI  - Targeted overexpression of leukemia inhibitory factor to preserve myocardium in a
      rat model of postinfarction heart failure.
AB  - OBJECTIVE: Myocardial infarction leads to cardiomyocyte loss. The cytokine
      leukemia inhibitory factor regulates the differentiation and growth of embryonic
      and adult heart tissue. This study examined the effects of gene transfer of
      leukemia inhibitory factor in infarcted rat hearts. METHODS: Lewis rats underwent
      ligation of the left anterior descending coronary artery and direct injection of
      adenovirus encoding leukemia inhibitory factor (n = 10) or null transgene as
      control (n = 10) into the myocardium bordering the ischemic area. A sham
      operation group (n = 10) underwent thoracotomy without ligation. After 6 weeks,
      the following parameters were evaluated: cardiac function with a pressure-volume
      conductance catheter, left ventricular geometry and architecture by histologic
      methods; myocardial fibrosis by Masson trichrome staining, apoptosis by terminal
      deoxynucleotidal transferase-mediated deoxyuridine triphosphate nick-end labeling
      assay, and cardiomyocyte size by immunofluorescence. RESULTS: Rats with
      overexpression of leukemia inhibitory factor had more preserved myocardium and
      less fibrosis in both the infarct and its border zone. The border zone in
      leukemia inhibitory factor-treated animals contained fewer apoptotic nuclei (1.6%
      +/- 0.1% vs 3.3% +/- 0.2%, P < .05) than that in control animals and demonstrated
      cardiomyocytes with larger cross-sectional areas (910 +/- 60 microm 2 vs 480 +/-
      30 microm 2 , P < .05). Leukemia inhibitory factor-treated animals had increased
      left ventricular wall thickness (2.1 +/- 0.1 mm vs 1.8 +/- 0.1 mm, P < .05) and
      less dilation of the left ventricular cavity (237 +/- 22 microL vs 301 +/- 16
      microL, P < .05). They also had improved cardiac function, as measured by maximum
      change in pressure over time (3950 +/- 360 mm Hg/s vs 2750 +/- 230 mm Hg/s, P <
      .05) and the slopes of the maximum change in pressure over time-end-diastolic
      volume relationship (68 +/- 5 mm Hg/[s . microL] vs 46 +/- 6 mm Hg/[s . microL],
      P < .05) and the preload recruitable stroke work relationship (89 +/- 10 mm Hg vs
      44 +/- 4 mm Hg, P < .05). CONCLUSIONS: Myocardial gene transfer of leukemia
      inhibitory factor preserved cardiac tissue, geometry, and function after
      myocardial infarction in rats.

PMID- 15573072
TI  - Long-segment tracheal stenosis: slide tracheoplasty and a multidisciplinary
      approach improve outcomes and reduce costs.
AB  - OBJECTIVE: Long-segment tracheal stenosis is rare, life-threatening, difficult,
      and expensive to treat. Management remains controversial. A multidisciplinary
      tracheal team was formed in 2000 to deal with a large number of children with
      airway problems referred for management. We review the effect of that service,
      comparing the era before and after the establishment of the multidisciplinary
      tracheal team. METHODS: From January 1998 through January 2004, 34 patients with
      long-segment tracheal stenosis (21 patients with cardiovascular anomalies)
      underwent surgical intervention. Cardiopulmonary bypass was used in all
      operations. Before the multidisciplinary tracheal team, pericardial patch
      tracheoplasty with or without an autograft technique was the preferred method of
      repair. After the multidisciplinary tracheal team, an integrated care plan
      preferring slide tracheoplasty was initiated, correcting cardiac lesions
      simultaneously. RESULTS: Before the establishment of the multidisciplinary
      tracheal team, pericardial patch tracheoplasty was performed in 15 of 19
      patients. Twelve patients had a suspended pericardial patch tracheoplasty, 2
      (17%) of whom died late after the operation. Of 3 patients who had had a simple
      unsuspended patch, 2 (67%) died early after the operation. Four patients were
      operated on with the tracheal autograft technique, 2 (50%) dying early in the
      postoperative period. After multidisciplinary tracheal team formation, in the era
      between 2001 and 2004, 15 patients were operated on with slide tracheoplasty, and
      there were 2 (13%) early postoperative deaths. A significant reduction in cost
      and duration of stay has been shown both in the intensive care unit and the
      hospital. CONCLUSION: Our data suggest that a formalized multidisciplinary team
      approach and a policy of primary slide tracheoplasty are beneficial in the
      management of children with long-segment tracheal stenosis.

PMID- 15573073
TI  - Cisplatin enhances apoptosis induced by a tumor-selective adenovirus expressing
      tumor necrosis factor-related apoptosis-inducing ligand.
AB  - BACKGROUND: Cancer cells frequently exhibit resistance to the cytotoxic effect of
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of
      TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin
      also has been shown to enhance adenoviral transgene expression. OBJECTIVE: This
      study aims to evaluate the ability of cisplatin to enhance the expression and the
      cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which
      expresses a green fluorescent protein-TRAIL fusion protein. METHODS: Cultured
      cancer cells and normal human cells were infected with Ad/gTRAIL with or without
      cisplatin pretreatment. Adenoviral transgene expression was determined by using
      flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity
      was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis
      enzyme-linked immunosorbent assay kit. RESULTS: Green fluorescent protein-TRAIL
      fusion protein expression was significantly enhanced by cisplatin pretreatment in
      cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to
      12-fold increase in green fluorescent protein fluorescence intensity across
      cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines
      (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with
      cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated
      cytotoxicity, as indicated by the drastic reduction of inhibitory concentration
      of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity
      noted in normal cells treated with both cisplatin and Ad/gTRAIL. CONCLUSION:
      Cisplatin pretreatment enhances Ad/gTRAIL cytotoxicity in malignant cells while
      not affecting normal cells. The mechanisms underlying this effect might include
      both enhancement of the susceptibility of cisplatin-treated cells to TRAIL and
      cisplatin-mediated enhancement of TRAIL expression in Ad/gTRAIL infected cells.
      These findings provide a rationale for development of Ad/gTRAIL-based therapy for
      thoracic malignancies.

PMID- 15573074
TI  - Value of F-18-fluorodeoxyglucose positron emission tomography after induction
      therapy of locally advanced bronchogenic carcinoma.
AB  - OBJECTIVES: Induction therapy is an important treatment option in locally
      advanced non-small cell lung cancer. F-18-fluorodeoxyglucose positron emission
      tomography (FDG-PET) has an important role in initial staging. The aim of this
      study was to assess the value of FDG-PET in restaging after induction therapy and
      in analyzing tumor viability, nodal status, distant metastases, and prognosis.
      METHODS: Forty-seven patients with locally advanced non-small cell lung cancer
      accepted for resection after induction therapy underwent FDG-PET. Images were
      interpreted visually for mediastinal nodal status and metastatic spread. The FDG
      accumulation in the tumor site was measured by using the maximum standardized
      uptake value. RESULTS: Unexpected metastases were detected by means of FDG-PET in
      9 patients. Surgical intervention was not performed in 8 patients with confirmed
      metastases. The rate of unexpected findings increased from complete radiologic
      remission (0%) over partial remission (9%) to no change (67%). The standardized
      uptake value was higher in tumors with (n = 26) than in those without (n = 11)
      histologic proof of viability (6.4 +/- 5.3 vs 2.9 +/- 1.6, P = .006). All
      patients with standardized uptake values of greater than 5.8 had viable tumors.
      Sensitivity, specificity, and negative predictive value were 81%, 64%, and 58%
      for tumor viability and 50%, 88%, and 85% for persistent mediastinal disease.
      Median survival after resection was greater than 56 months for patients with
      tumor standardized uptake values of less than 4 and 19 months for patients with
      standardized uptake values of 4 or greater ( P < .001). CONCLUSION: FDG-PET helps
      in the selection of patients for resection after induction therapy. It can be
      used to detect unexpected distant metastases, especially after poor response to
      induction therapy. Its high negative predictive value in mediastinal restaging
      allows for omission of repeat mediastinoscopy. Tumor standardized uptake value
      after induction is a prognostic factor.

PMID- 15573075
TI  - Experimental generation of a tissue-engineered functional and vascularized
      trachea.
AB  - OBJECTIVE: We sought to grow in vitro functional smooth muscle cells,
      chondrocytes, and respiratory epithelium on a biologic, directly vascularized
      matrix as a scaffold for tracheal tissue engineering. METHODS: Ten- to 15-cm-long
      free jejunal segments with their own vascular pedicle were harvested and
      acellularized from donor pigs (n = 10) and used as a vascular matrix. Autologous
      costal chondrocytes, smooth muscle cells, and respiratory epithelium and
      endothelial progenitor cells were first cultured in vitro and then disseminated
      on the previously acellularized vascular matrix. Histologic, immunohistologic,
      molecular imaging, and Western blotting studies were then performed to assess
      cell viability. RESULTS: The endothelial progenitor cells re-endothelialized the
      matrix to such an extent that endothelial cell viability was uniformly documented
      through 2-(18F)-fluoro-2'-deoxyglucose positron emission tomography. This
      vascularized scaffold was seeded with functional (according to Western blot
      analysis) smooth muscle cells and successfully reseeded with viable ciliated
      respiratory epithelium. Chondrocyte growth and production of extracellular
      cartilaginous matrix was observed as soon as 2 weeks after their culture.
      CONCLUSIONS: The fundamental elements for a bioartificial trachea were
      successfully engineered in vitro in a direct vascularized 10- to 15-cm-long
      bioartificial matrix. Future experimental work will be directed to give them a 3
      dimensional aspect and a biomechanical profile of a functioning trachea.

PMID- 15573076
TI  - Monitoring the performance of residents during training in off-pump coronary
      surgery.
AB  - OBJECTIVE: Control charts (eg, cumulative sum charts) plot changes in performance
      with time and can alert a surgeon to suboptimal performance. They were used to
      compare performance of off-pump coronary artery bypass surgery between a
      consultant and four resident surgeons and to compare performance of off-pump
      coronary artery bypass surgery and conventional coronary artery bypass grafting
      within surgeons. METHODS: Data were analyzed for consecutive patients undergoing
      coronary artery bypass grafting who were operated on by one consultant or one of
      four residents. Conversions were analyzed by intention to treat. Perioperative
      death or one or more of 10 adverse events constituted failure. Predicted risks of
      failure for individual patients were derived from the study population. Variable
      life-adjusted displays and risk-adjusted sequential probability ratio test charts
      were plotted. RESULTS: Data for 1372 patients were analyzed; 769 of the
      procedures were off-pump coronary artery bypass operations (56.0%). The
      consultant operated on 382 patients (293 off-pump, 76.7%), and the residents
      operated on 990 (474 off-pump, 47.9%). Patients operated on by residents tended
      to be older, more obese, more likely to require an urgent operation, and more
      likely to need a circumflex artery graft but less likely to have triple-vessel
      disease. There were 7 conversions (consultant 5, residents 2). The overall
      failure rate was 8.5% (9.2% for consultant's operations and 8.2% for residents'
      operations), including 10 deaths (0.7%). Predicted and observed risks of failure
      were similar for all five surgeons. After 100 off-pump coronary artery bypass
      operations, performance was the same or better for the residents as for the
      consultant. For all surgeons, performance was the same or better for off-pump as
      for conventional coronary artery bypass grafting. CONCLUSIONS: Off-pump coronary
      artery bypass surgery can be safely taught to cardiothoracic residents.
      Implementation of continuous performance monitoring for residents is practicable.

PMID- 15573077
TI  - Recurrent mitral regurgitation after annuloplasty for functional ischemic mitral
      regurgitation.
AB  - OBJECTIVES: We sought to characterize the temporal return of mitral regurgitation
      after annuloplasty for functional ischemic mitral regurgitation; to identify its
      predictors, particularly with respect to annuloplasty type; and to determine
      whether annuloplasty type influences survival. METHODS: From April 1985 through
      November 2002, 585 patients underwent annuloplasty alone for repair of functional
      ischemic mitral regurgitation, generally with concomitant coronary
      revascularization (95%). A flexible band (Cosgrove) was used in 68%, a rigid ring
      (Carpentier) in 21%, and bovine pericardial annuloplasty (Peri-Guard) in 11%. Six
      hundred seventy-eight postoperative echocardiograms were available in 422
      patients to assess the time course of postoperative mitral regurgitation and its
      correlates. Most echocardiograms were performed early after the operation
      (median, 8 days); 17% were performed at 1 year or beyond. RESULTS: During the
      first 6 months after repair, the proportion of patients with 0 or 1+ mitral
      regurgitation decreased from 71% to 41%, whereas the proportion with 3+ or 4+
      regurgitation increased from 13% to 28% ( P < .0001); the regurgitation grade was
      stable thereafter. The temporal pattern of development of 3+ or 4+ regurgitation
      was similar for Cosgrove bands and Carpentier rings (25%) but substantially worse
      for Peri-Guard annuloplasties (66%). Small annuloplasty size did not influence
      postoperative regurgitation grade ( P = .2), although Cosgrove bands were used in
      most patients receiving 26- and 28-mm annuloplasties. Freedom from reoperation
      was 97% at 5 years. Annuloplasty type was not associated with survival.
      CONCLUSIONS: Although initial mitral valve replacement would eliminate the risk
      of postoperative mitral regurgitation, this strategy has been associated with
      reduced survival. Therefore the development of additional techniques is necessary
      to achieve more secure repair of functional ischemic mitral regurgitation.

PMID- 15573078
TI  - The evolution of ischemic spinal cord injury in function, cytoarchitecture, and
      inflammation and the effects of adenosine A2A receptor activation.
AB  - OBJECTIVE: Spinal cord ischemia/reperfusion injury involves multiple factors that
      may be modulated by adenosine A 2A receptor activation. This study defines injury
      progression in terms of function, cytoarchitecture, and inflammation and assesses
      whether adenosine A 2A receptor activation by ATL-146e limits injury progression.
      METHODS: Mature swine were divided into 3 groups: sham thoracotomy, IR (30
      minutes of ischemia followed by reperfusion), and ATL (ischemia/reperfusion with
      ATL-146e administration for the first 3 hours of reperfusion). Subgroups were
      killed at 0, 3, 6, 12, 24, and 48 hours after reperfusion. Function was followed
      up with Tarlov scores. Spinal cord tissue was evaluated for neuronal viability,
      microtubule-associated protein-2 immunohistochemistry, and neutrophil
      sequestration (myeloperoxidase assay). Spinal cord tissue, cerebrospinal fluid,
      and serum were evaluated for tumor necrosis factor-alpha by enzyme-linked
      immunosorbent assay. RESULTS: Function was significantly impaired at 24, 36, and
      48 hours in the IR group compared with the sham and ATL groups ( P < .05).
      Neuronal viability and microtubule-associated protein-2 staining were
      significantly preserved in the sham and ATL groups compared with the IR group at
      24 and 48 hours ( P < .05). Spinal cord myeloperoxidase levels were significantly
      higher in the IR group than in the sham and ATL groups at 24 and 48 hours.
      Although negligible in serum and cerebrospinal fluid, tumor necrosis factor-alpha
      levels in the spinal cord peaked significantly higher in the IR group compared
      with the sham and ATL groups at 6 and 24 hours ( P < .05). CONCLUSIONS: Spinal
      cord ischemia/reperfusion induced changes in neutrophil sequestration,
      microtubule-associated protein-2 expression, and neuronal viability within 24
      hours of reperfusion. Spinal cord tumor necrosis factor-alpha increased
      significantly by 6 to 12 hours after reperfusion. Adenosine A 2A receptor
      activation attenuates spinal cord inflammation, which may be critical for the
      preservation of neuronal function and cytoarchitecture after
      ischemia/reperfusion.

PMID- 15573079
TI  - Improved survival after living-donor lobar lung transplantation.
AB  - OBJECTIVE: Survival after living-donor lobar lung transplantation has been
      reported to be similar to that after cadaveric lung transplantation. The purpose
      of this study was to summarize our 5-year experience of living-donor lobar lung
      transplantation for critically ill patients. METHODS: Between October 1998 and
      April 2004, we performed living-donor lobar lung transplantation in 30 critically
      ill patients with various lung diseases, including 5 (17%) patients on a
      ventilator. Mean age was 30.4 years (range, 8-55 years). Postoperative management
      included slow weaning from a ventilator, relatively low-dose immunosuppressants,
      and careful rejection monitoring on the basis of radiographic and clinical
      findings without transbronchial lung biopsy. RESULTS: The average duration of
      mechanical ventilation was 15.4 days, intensive care unit stay was 23.5 days, and
      hospital stay was 64.6 days. Clinically judged acute rejection occurred at an
      average rate of 1.5 episodes per patient, but infection occurred in only one
      patient during the first month. In spite of the complicated postoperative course,
      all patients were discharged without oxygen inhalation. Four patients had
      unilateral bronchiolitis obliterans syndrome, but the decrease in their forced
      expiratory volume in 1 second values stopped within 9 months. All 30 recipients
      are currently alive, with a follow-up period of 1 to 66 months. All donors have
      returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung
      transplantation can be applied to both pediatric and adult patients with very
      limited life expectancies. It might provide better survival than conventional
      cadaveric lung transplantation.

PMID- 15573080
TI  - Successful use of one dose of recombinant factor VIIa to control severe bleeding
      after emergency aortic arch replacement in deep hypothermic circulatory arrest.

PMID- 15573081
TI  - Atrioventricular discordance with ventriculoarterial concordance: A remaining
      indication for the atrial switch operation.

PMID- 15573082
TI  - Dysphagia: an unusual presentation of giant aneurysm of the right coronary artery
      and supravalvular aortic stenosis in Williams syndrome.

PMID- 15573083
TI  - Inhaled prostacyclin is safe, effective, and affordable in patients with
      pulmonary hypertension, right-heart dysfunction, and refractory hypoxemia after
      cardiothoracic surgery.

PMID- 15573084
TI  - Henry T. Bahnson, Hopkins, and harmonica.

PMID- 15573085
TI  - Who will regulate the regulators?

PMID- 15573086
TI  - Intergenomic consensus in multifactorial inheritance loci: the case of multiple
      sclerosis.
AB  - Genetic linkage and association studies define chromosomal regions, quantitative
      trait loci (QTLs), which influence the phenotype of polygenic diseases. Here, we
      describe a global approach to determine intergenomic consensus of those regions
      in order to fine map QTLs and select particularly promising candidate genes for
      disease susceptibility or other polygenic traits. Exemplarily, human multiple
      sclerosis (MS) susceptibility regions were compared for sequence similarity with
      mouse and rat QTLs in its animal model experimental allergic encephalomyelitis
      (EAE). The number of intergenomic MS/EAE consensus genes (295) is significantly
      higher than expected if the animal model was unrelated to the human disease.
      Hence, this approach contributes to the empirical evaluation of animal models for
      their applicability to the study of human diseases.

PMID- 15573087
TI  - IL-10 stimulatory effects on human NK cells explored by gene profile analysis.
AB  - The molecular mechanisms underlying the increase of natural killer (NK) cell
      anticancer activity mediated by interleukin (IL)-10 have not been elucidated. The
      aim of this study was to identify potential molecular mediators of IL-10
      stimulatory effects by exploring the NK cell gene display induced by this
      cytokine. Gene profile was determined by high-throughput cDNA microarray and
      quantitative real-time PCR. In vitro, NK cells resting or conditioned with IL-10
      were tested for cytotoxicity, migration and proliferation. IL-10 enhanced mRNA
      levels of cell activation/cytotoxicity-related genes (eg secretogranin, TIA-1,
      HMG-1, interferon-inducible genes) not upregulated by IL-2. In line with these
      findings, IL-10 increased NK cell in vitro cytotoxicity against Daudi cells.
      Unlike IL-2, IL-10 did not show any significant effect on NK cell in vitro
      proliferation and migration. However, gene profile analysis showed that IL-10
      increased the expression of cell migration-related genes (eg L-selectin, vascular
      endothelium growth factor receptor-1, plasminogen activator, tissue; formyl
      peptide receptor, lipoxin A4 receptor), which might support a stimulatory effect
      not evident with the in vitro functional assay. Overall, gene profiling allowed
      us to formulate new hypotheses regarding the molecular pathways underlying the
      stimulatory effects of IL-10 on NK cells, supporting further investigation aimed
      at defining its role in cancer immune rejection.

PMID- 15573088
TI  - Neuronal expression of the transcription factor Gli1 using the Talpha1 alpha
      tubulin promoter is neuroprotective in an experimental model of Parkinson's
      disease.
AB  - Nigrostriatal neurons degenerate during Parkinson's disease. Experimentally,
      neurotoxins such as 6-hydroxydopamine (6-OHDA) in rodents, and MPTP in mice and
      non-human primates, are used to model the disease-induced degeneration of
      midbrain dopaminergic neurons. Glial-cell-derived neurotrophic factor (GDNF) is a
      very powerful neuroprotector of dopaminergic neurons in all species examined.
      However, recent reports have indicated the possibility that GDNF may, in the long
      term and if expressed in an unregulated manner, exert untoward effects on
      midbrain dopaminergic neuronal structure and function. Although GDNF remains a
      powerful neurotrophin, the search for alternative therapies based on alternative
      and complementary mechanisms of action to GDNF is warranted. Recently,
      recombinant adenovirus-derived vectors encoding the differentiation factor Sonic
      Hedgehog (Shh) and its downstream transcriptional activator (Gli1) were shown to
      protect dopaminergic neurons in the substantia nigra pars compacta from 6-OHDA
      induced neurotoxicity in rats in vivo. A pancellular human CMV (hCMV) promoter
      was used to drive the expression of both Shh and Gli1. Since Gli1 is a
      transcription factor and therefore exerts its actions intracellularly, we decided
      to test whether expression of Gli1 within neurons would be effective for
      neuroprotection. We demonstrate that neuronal-specific expression of Gli1 using
      the neuron-specific Talpha1 alpha-tubulin (Talpha1) promoter was neuroprotective,
      and its efficiency was comparable to the pancellular strong viral hCMV promoter.
      These results suggest that expression of the transcription factor Gli1 solely
      within neurons is neuroprotective for dopaminergic neurons in vivo and,
      furthermore, that neuronal-specific promoters are effective within the context of
      adenovirus-mediated gene therapy-induced neuroprotection of dopaminergic midbrain
      neurons. Since cell-type specific promoters are known to be weaker than the viral
      hCMV promoter, our data demonstrate that neuronal-specific expression of
      transcription factors is an effective, specific, and sufficient targeted approach
      for neurological gene therapy applications, potentially minimizing side effects
      due to unrestricted promiscuous gene expression within target tissues.

PMID- 15573089
TI  - Cloning around.

PMID- 15573090
TI  - There goes the neighbourhood: Eps8 joins the barbed-end crowd.

PMID- 15573092
TI  - Tudor domains track down DNA breaks.

PMID- 15573093
TI  - A second RING to destroy p27(Kip1).

PMID- 15573094
TI  - Invasive growth: a two-way street for semaphorin signalling.

PMID- 15573095
TI  - Progressing actin: Formin as a processive elongation machine.

PMID- 15573098
TI  - Intra-nuclear microtubules and a mitotic spindle orientation checkpoint.
AB  - Cells of the fission yeast Schizosaccharomyces pombe have a checkpoint mechanism
      that reportedly monitors the orientation of the mitotic spindle. Astral
      microtubules in pre-anaphase spindles are thought to contact the contractile
      actin ring at the plasma membrane in order to rotate the spindle and to sense
      spindle orientation. Here, we show that these microtubules are actually inside
      the nuclear envelope.

PMID- 15573099
TI  - Strategies to overcome resistance to targeted protein kinase inhibitors.
AB  - Selective inhibition of protein tyrosine kinases is gaining importance as an
      effective therapeutic approach for the treatment of a wide range of human
      cancers. However, as extensively documented for the BCR-ABL oncogene in imatinib
      treated leukaemia patients, clinical resistance caused by mutations in the
      targeted oncogene has been observed. Here, we look at how structural and
      mechanistic insights from imatinib-insensitive Bcr-Abl have been exploited to
      identify second-generation drugs that override acquired target resistance. These
      insights have created a rationale for the development of either multi-targeted
      protein kinase inhibitors or cocktails of selective antagonists as antitumour
      drugs that combine increased therapeutic potency with a reduced risk of the
      emergence of molecular resistance.

PMID- 15573100
TI  - Development of TGF-beta signalling inhibitors for cancer therapy.
AB  - The transforming growth factor-beta (TGF-beta) superfamily of ligands has a
      pivotal role in the regulation of a wide variety of physiological processes from
      development to pathogenesis. Since the discovery of the prototypic member, TGF
      beta, almost 20 years ago, there have been tremendous advances in our
      understanding of the complex biology of this superfamily. Deregulation of TGF
      beta has been implicated in the pathogenesis of a variety of diseases, including
      cancer and fibrosis. Here we present the rationale for evaluating TGF-beta
      signalling inhibitors as cancer therapeutics, the structures of small-molecule
      inhibitors that are in development and the targeted drug discovery model that is
      being applied to their development.

PMID- 15573101
TI  - Cyclodextrin-based pharmaceutics: past, present and future.
AB  - Cyclodextrins are cyclic oligomers of glucose that can form water-soluble
      inclusion complexes with small molecules and portions of large compounds. These
      biocompatible, cyclic oligosaccharides do not elicit immune responses and have
      low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical
      applications for numerous purposes, including improving the bioavailability of
      drugs. Current cyclodextrin-based therapeutics are described and possible future
      applications discussed. Cyclodextrin-containing polymers are reviewed and their
      use in drug delivery presented. Of specific interest is the use of cyclodextrin
      containing polymers to provide unique capabilities for the delivery of nucleic
      acids.

PMID- 15573102
TI  - Challenges in bringing the bench to bedside in drug development for SLE.
AB  - It is now widely accepted that the current standard of care for systemic lupus
      erythematosus (SLE) patients is inadequate. There has not been a new medication
      approved for this disease in thirty years. Attempts to develop and test new drugs
      have been ongoing since the mid-1990s, but have encountered formidable obstacles.
      Current models for lupus pathogenesis have provided a theoretical framework for
      understanding how heterogeneous genetic defects might combine in various ways to
      increase susceptibility to SLE in different individuals, and could have important
      implications for new drug development. With the current burst of drug discovery
      and increased public awareness of SLE, the impetus to overcome these obstacles
      has never been greater.

PMID- 15573103
TI  - Making protein interactions druggable: targeting PDZ domains.
AB  - Modulating protein-protein interactions involved in disease pathways is an
      attractive strategy for developing drugs, but remains a challenge to achieve. One
      approach is to target certain domains within proteins that mediate these
      interactions. One example of such a domain is the PDZ domain, which is involved
      in interactions between many different proteins in a variety of cellular
      contexts. Because PDZ domains have well-defined binding sites, they are promising
      targets for drug discovery. However, there is still much to learn about the
      function of these domains before drugs targeting PDZ interactions can become a
      reality.

PMID- 15573104
TI  - Pharmaceutical patent challenges--time for reassessment?
AB  - For nearly 15 years after the passage of the Hatch-Waxman Act in 1984, generics
      drug companies took little advantage of its provisions, which provided financial
      incentives to them for challenging the patents of branded pharmaceutical
      products. However, during the past 3-5 years, generics manufacturers have
      dramatically increased the number of patent challenges. Although these challenges
      can certainly benefit consumers and payers, the number of challenges puts many
      innovator companies at risk, which they argue is detrimental to future R&D
      spending. If many of the challenges are successful, then the increase in
      challenges could in turn be detrimental to generics, and the system itself might
      therefore be due for a re-balance.

PMID- 15573105
TI  - Space materials research: hanging by a thread.

PMID- 15573106
TI  - Rational development of new materials--putting the cart before the horse?

PMID- 15573108
TI  - Optical materials: Self-assembly reaches new heights.

PMID- 15573109
TI  - Wetting dynamics: Spreading of metallic drops.

PMID- 15573110
TI  - Magnetic memory: A signal boost is in order.

PMID- 15573111
TI  - Microfluidics: Magnetic chaperones for droplets.

PMID- 15573112
TI  - Magnetoelectrics: A new route to magnetic ferroelectrics.

PMID- 15573113
TI  - Material witness: Watching paint dry.

PMID- 15573114
TI  - Aurora-kinase inhibitors as anticancer agents.
AB  - Errors in mitosis can provide a source of the genomic instability that is
      typically associated with tumorigenesis. Many mitotic regulators are aberrantly
      expressed in tumour cells. These proteins could therefore make useful therapeutic
      targets. The kinases Aurora-A, -B and -C represent a family of such targets and
      several small-molecule inhibitors have been shown to block their function. Not
      only have these inhibitors advanced our understanding of mitosis, but,
      importantly, their in vivo antitumour activity has recently been reported. What
      have these studies taught us about the therapeutic potential of inhibiting this
      family of kinases?

PMID- 15573115
TI  - Targeting the mitogen-activated protein kinase cascade to treat cancer.
AB  - The RAS-mitogen activated protein kinase (MAPK) signalling pathway has long been
      viewed as an attractive pathway for anticancer therapies, based on its central
      role in regulating the growth and survival of cells from a broad spectrum of
      human tumours. Small-molecule inhibitors designed to target various steps of this
      pathway have entered clinical trials. What have we recently learned about their
      safety and effectiveness? Will the MAPK pathway prove amenable to therapeutic
      intervention?

PMID- 15573116
TI  - Regulation of the cytoskeleton: an oncogenic function for CDK inhibitors?
AB  - Cyclin-dependent kinase inhibitors (CKIs) are well known inhibitors of cell
      proliferation. Their activity is disrupted in many tumour types. Recent studies
      show that some of these proteins have interesting alternative functions, acting
      in the cytoplasm to regulate Rho signalling and thereby controlling cytoskeletal
      organization and cell migration. The upregulation of CKIs in the cytoplasm of
      many cancer cells indicates that although loss of nuclear CKIs is important for
      cancer cell proliferation, gain of cytoplasmic CKI function might be involved in
      tumour invasion and metastasis.

PMID- 15573117
TI  - Gefitinib--a novel targeted approach to treating cancer.
AB  - Twenty years after the epidermal growth factor receptor (EGFR) was identified as
      a potential anticancer target, the EGFR inhibitor gefitinib (Iressa; AstraZeneca)
      has been approved for the treatment of patients with advanced non-small-cell lung
      cancer in many countries. Studies have indicated its potential for treating
      patients with other types of solid tumours. Investigation of gefitinib has not
      only increased our knowledge about the biology of EGFR signalling, but is
      contributing to our evolving understanding of which tumours are EGFR dependent.

PMID- 15573118
TI  - The role of the unfolded protein response in tumour development: friend or foe?
AB  - Having accumulated mutations that overcome cell-cycle and apoptotic checkpoints,
      the main obstacle to survival faced by a cancer cell is the restricted supply of
      nutrients and oxygen. These conditions impinge on protein folding in the
      endoplasmic reticulum and activate a largely cytoprotective signalling pathway
      called the unfolded protein response. Prolonged activation of this response can,
      however, terminate in apoptosis. Recent delineation of the components of this
      response, coupled with several clinical studies, indicate that it is uniquely
      poised to have a role in regulating the balance between cancer cell death,
      dormancy and aggressive growth, as well as altering the sensitivity of solid
      tumours to chemotherapeutic agents.

PMID- 15573119
TI  - Netrin-1 and its receptors in tumorigenesis.
AB  - Netrin-1 and its receptors DCC (deleted in colorectal cancer) and the UNC5
      orthologues (human UNC5A-D and rodent UNC5H1-4) define a new mechanism for both
      the positive (induction) and negative (suppression) regulation of apoptosis.
      Accumulating evidence implies that for human cancers, this positive signalling
      pathway is frequently inactivated. Surprisingly, binding of netrin-1 to its
      receptors inhibits tumour suppressor p53-dependent apoptosis, and p53 is directly
      involved in transcriptional regulation of netrin-1 and its receptors. So, the
      netrin-1 receptor pathways probably play an important part in tumorigenesis.

PMID- 15573120
TI  - CpG island methylator phenotype in cancer.
AB  - DNA hypermethylation in CpG-rich promoters is now recognized as a common feature
      of human neoplasia. However, the pathophysiology of hyper-methylation (why, when,
      where) remains obscure. Cancers can be classified according to their degree of
      methylation, and those cancers with high degrees of methylation (the CpG island
      methylator phenotype, or CIMP) represent a clinically and aetiologically distinct
      group that is characterized by 'epigenetic instability'. Furthermore, CIMP
      associated cancers seem to have a distinct epidemiology, a distinct histology,
      distinct precursor lesions and distinct molecular features.

PMID- 15573121
TI  - Gene map of the extended human MHC.
AB  - The major histocompatibility complex (MHC) is the most important region in the
      vertebrate genome with respect to infection and autoimmunity, and is crucial in
      adaptive and innate immunity. Decades of biomedical research have revealed many
      MHC genes that are duplicated, polymorphic and associated with more diseases than
      any other region of the human genome. The recent completion of several large
      scale studies offers the opportunity to assimilate the latest data into an
      integrated gene map of the extended human MHC. Here, we present this map and
      review its content in relation to paralogy, polymorphism, immune function and
      disease.

PMID- 15573122
TI  - Dog star rising: the canine genetic system.
AB  - Purebred dogs are providing invaluable information about morphology, behaviour
      and complex diseases, both of themselves and humans, by supplying tractable
      populations in which to map genes that control those processes. The
      diversification of dog breeds has led to the development of breeds enriched for
      particular genetic disorders, the mapping and cloning of which have been
      facilitated by the availability of the canine genome map and sequence. These
      tools have aided our understanding of canine population genetics, linkage
      disequilibrium and haplotype sharing in the dog, and have informed ongoing
      efforts of the need to identify quantitative trait loci that are important in
      complex traits.

PMID- 15573123
TI  - The genetics of cell death: approaches, insights and opportunities in Drosophila.
AB  - Cell death is ubiquitous in metazoans and involves the action of an
      evolutionarily conserved process known as programmed cell death or apoptosis. In
      Drosophila melanogaster, it is now uniquely possible to screen for genes that
      determine the fate - life or death - of any cell or population of cells during
      development and in the adult. This review describes these genetic approaches and
      the key insights into cell-death mechanisms that have been obtained, as well as
      the outstanding questions that these techniques can help to answer.

PMID- 15573124
TI  - When sugars guide axons: insights from heparan sulphate proteoglycan mutants.
AB  - Although there have previously been hints that heparan sulphate proteoglycans
      (HSPGs) are important for axon guidance, as they are for many other biological
      processes, there has been little in vivo evidence for interaction with known axon
      guidance pathways. Genetic analyses of fly, mouse, nematode and zebrafish mutants
      now confirm the role of HSPGs in axon guidance and are beginning to show that
      they might have a key role in modulating the action of axon-guidance ligands and
      receptors.

PMID- 15573125
TI  - Toxicogenomics and systems toxicology: aims and prospects.
AB  - Toxicogenomics combines transcript, protein and metabolite profiling with
      conventional toxicology to investigate the interaction between genes and
      environmental stress in disease causation. The patterns of altered molecular
      expression that are caused by specific exposures or disease outcomes have
      revealed how several toxicants act and cause disease. Despite these success
      stories, the field faces noteworthy challenges in discriminating the molecular
      basis of toxicity. We argue that toxicology is gradually evolving into a systems
      toxicology that will eventually allow us to describe all the toxicological
      interactions that occur within a living system under stress and use our knowledge
      of toxicogenomic responses in one species to predict the modes-of-action of
      similar agents in other species.

PMID- 15573126
TI  - George Beadle: from genes to proteins.
AB  - George W. Beadle's life spanned much of the period during which genetics changed
      from an abstract to a molecular science. Beadle himself catalysed the transition
      from classical to molecular genetics when, together with Edward Tatum, he
      discovered that each gene is linked to the production of a protein. This article
      traces his life from a modest farm to the centre of biology and a principal role
      in the development of the scientific enterprise.

PMID- 15573127
TI  - Ensuring the appropriate use of genetic tests.
AB  - Ensuring the correct use of genetic tests is an important challenge for health
      policy makers. Many new genetic tests will identify susceptibility to common
      diseases or adverse drug responses. Some will lead to new prevention
      opportunities, but others will have minimal clinical value. Statutory regulation
      alone cannot guarantee appropriate use. Other strategies, including resource
      allocation and matters related to clinical governance - such as practice
      guideline development and health-provider education - are also important.

PMID- 15573128
TI  - Consequences of regulated pre-mRNA splicing in the immune system.
AB  - Alternative splicing is widely recognized to be a ubiquitous and crucial
      mechanism for generating protein diversity and regulating protein expression.
      Numerous immunologically relevant genes have been found to undergo alternative
      splicing; however, there has been little effort to develop a coherent picture of
      how alternative splicing might be used as a general mechanism to regulate the
      function of the immune system. In this review, I summarize the mechanisms by
      which splicing is controlled in T cells, and discuss the role of alternative
      splicing and alternative isoform expression in the regulation of T-cell
      activation and function.

PMID- 15573129
TI  - Mechanisms and functional significance of tumour-induced dendritic-cell defects.
AB  - The failure of the immune system to provide protection against tumour cells is an
      important immunological problem. It is now evident that inadequate function of
      the host immune system is one of the main mechanisms by which tumours escape from
      immune control, as well as an important factor that limits the success of cancer
      immunotherapy. In recent years, it has become increasingly clear that defects in
      dendritic cells have a crucial role in non-responsiveness to tumours. This
      article focuses on the functional consequences and recently described mechanisms
      of the dendritic-cell defects in cancer.

PMID- 15573130
TI  - War and peace at mucosal surfaces.
AB  - That we live with numerous bacteria in our gut without any adverse effects is a
      remarkable feat by the body's immune system, particularly considering the wealth
      of sensing and effector systems that are available to trigger inflammatory or
      innate immune responses to microbial intrusion. So, a fine line seems to exist
      between the homeostatic balance maintained in the presence of commensal gut flora
      and the necessarily destructive response to bacterial pathogens that invade the
      gut mucosa. This review discusses the mechanisms for establishing and controlling
      the 'dialogue' between unresponsiveness and initiation of active immune defences
      in the gut. Si vis pacem, para bellum. (If you wish for peace, prepare for war.).

PMID- 15573131
TI  - A BAF-centred view of the immune system.
AB  - Chromatin structure dictates whether DNA templates are accessible to nuclear
      proteins; therefore, it is tightly regulated. To reconfigure chromatin, cells
      often mobilize 'chromatin-remodelling complexes' that use energy to disrupt
      histone-DNA contacts. BAF complexes, which are related to the yeast SWI-SNF
      complex, are the prototypical mammalian chromatin-remodelling complexes. In the
      past few years, studies have revealed the crucial and diverse roles of BAF
      complexes in the regulation of the immune system - from lymphocyte development to
      immune responses. This review surveys these advances, highlighting the general
      insights these studies provide into the modes of action of BAF complexes, and it
      concludes with a discussion of some of the key opportunities and challenges in
      this field.

PMID- 15573132
TI  - The immunogenetics of asthma and eczema: a new focus on the epithelium.
AB  - Asthma and eczema (atopic dermatitis) are the most common chronic diseases of
      childhood. These diseases are characterized by the production of high levels of
      immunoglobulin E in response to common allergens. Their development depends on
      both genetic and environmental factors. Over the past few years, several genes
      and genetic loci that are associated with increased susceptibility to asthma and
      atopic dermatitis have been described. Many of these genes are expressed in the
      mucosa and epidermis, indicating that events at epithelial-cell surfaces might be
      driving disease processes. This review describes the mechanisms of innate
      epithelial immunity and the role of microbial factors in providing protection
      from disease development. Understanding events at the epithelial-cell surface
      might provide new insights for the development of new treatments for inflammatory
      epithelial disease.

PMID- 15573133
TI  - Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1
      diabetes.
AB  - Without a doubt, rodent models have been instrumental in describing pathways that
      lead to pancreatic beta-cell destruction, evaluating potential causes of type 1
      diabetes and providing proof-of-principle for the potential of immune-based
      interventions. However, despite more than two decades of productive research, we
      are still yet to define an initiating autoantigen for the human disease, to
      determine the precise mechanisms of beta-cell destruction in humans and to design
      interventions that prevent or cure type 1 diabetes. In this Perspective article,
      we propose that a major philosophical change would benefit this field, a
      proposition that is based on evaluation of situations in which rodent models have
      provided useful guidance and in which they have led to disappointments.

PMID- 15573134
TI  - AKAP signalling complexes: focal points in space and time.
AB  - Multiprotein signalling networks create focal points of enzyme activity that
      disseminate the intracellular action of many hormones and neurotransmitters.
      Accordingly, the spatio-temporal activation of protein kinases and phosphatases
      is an important factor in controlling where and when phosphorylation events
      occur. Anchoring proteins provide a molecular framework that orients these
      enzymes towards selected substrates. A-kinase anchoring proteins (AKAPs) are
      signal-organizing molecules that compartmentalize various enzymes that are
      regulated by second messengers.

PMID- 15573135
TI  - The complex architecture of oxygenic photosynthesis.
AB  - Oxygenic photosynthesis is the principal producer of both oxygen and organic
      matter on earth. The primary step in this process - the conversion of sunlight
      into chemical energy - is driven by four, multisubunit, membrane-protein
      complexes that are known as photosystem I, photosystem II, cytochrome b(6)f and F
      ATPase. Structural insights into these complexes are now providing a framework
      for the exploration not only of energy and electron transfer, but also of the
      evolutionary forces that shaped the photosynthetic apparatus.

PMID- 15573136
TI  - Meiosis: cell-cycle controls shuffle and deal.
AB  - Meiosis is the type of cell division that gives rise to eggs and sperm. Errors in
      the execution of this process can result in the generation of aneuploid gametes,
      which are associated with birth defects and infertility in humans. Here, we
      review recent findings on how cell-cycle controls ensure the coordination of
      meiotic events, with a particular focus on the segregation of chromosomes.

PMID- 15573137
TI  - Viral hijacking of G-protein-coupled-receptor signalling networks.
AB  - Viruses use a surprising diversity of approaches to hijack G-protein-coupled
      receptors and harness their activated intracellular signalling pathways. All of
      these approaches ultimately function to ensure viral replicative success and
      often contribute to their pathogenesis. Indeed, a single virus might deploy a
      repertoire of these strategies to regulate key intracellular survival,
      proliferative and chemotactic pathways. Understanding the contribution of these
      biochemical routes to viral pathogenesis might facilitate the development of
      effective target-specific therapeutic strategies against viral diseases.

PMID- 15573138
TI  - The double-stranded-RNA-binding motif: interference and much more.
AB  - RNA duplexes have been catapulted into the spotlight by the discovery of RNA
      interference and related phenomena. But double-stranded and highly structured
      RNAs have long been recognized as key players in cell processes ranging from RNA
      maturation and localization to the antiviral response in higher organisms.
      Penetrating insights into the metabolism and functions of such RNAs have come
      from the identification and study of proteins that contain the double-stranded
      RNA-binding motif.

PMID- 15573139
TI  - Making sense of it all: bacterial chemotaxis.
AB  - Bacteria must be able to respond to a changing environment, and one way to
      respond is to move. The transduction of sensory signals alters the concentration
      of small phosphorylated response regulators that bind to the rotary flagellar
      motor and cause switching. This simple pathway has provided a paradigm for
      sensory systems in general. However, the increasing number of sequenced bacterial
      genomes shows that although the central sensory mechanism seems to be common to
      all bacteria, there is added complexity in a wide range of species.

PMID- 15573140
TI  - The DNA-polymerase-X family: controllers of DNA quality?
AB  - Synthesis of the genetic material of the cell is achieved by a large number of
      DNA polymerases. Besides replicating the genome, they are involved in DNA-repair
      processes. Recent studies have indicated that certain DNA-polymerase-X-family
      members can synthesize unusual DNA structures, and we propose that these DNA
      structures might serve as 'flag wavers' for the induction of DNA-repair and/or
      DNA-damage-checkpoint pathways.

PMID- 15573141
TI  - Diabetic cardiomyopathy: recent evidence from mouse models of type 1 and type 2
      diabetes.
AB  - Diabetic cardiomyopathy is defined as ventricular dysfunction of the diabetic
      heart in the absence of coronary artery disease. With the use of both in vivo and
      ex vivo techniques to assess cardiac phenotype, reduced contractile performance
      can be observed in experiments with mouse models of both type 1 (insulin
      deficient) and type 2 (insulin-resistant) diabetes. Both systolic dysfunction
      (reduced left ventricular pressures and decreased cardiac output) and diastolic
      dysfunction (impaired relaxation) is observed in diabetic hearts, along with
      enhanced susceptibility to ischemic injury. Metabolism is also altered in
      diabetic mouse hearts: glucose utilization is reduced and fatty acid utilization
      is increased. The use of genetically engineered mice has provided a powerful
      experimental approach to test mechanisms that may be responsible for the
      deleterious effects of diabetes on cardiac function.

PMID- 15573142
TI  - The expression and function of a group VIA calcium-independent phospholipase A2
      (iPLA2beta) in beta-cells.
AB  - Many cells express a Group VIA phospholipase A2, designated iPLA2beta, that does
      not require calcium for activation, is stimulated by ATP, and is sensitive to
      inhibition by a bromoenol lactone suicide substrate (BEL). Studies in various
      cell systems have led to the suggestion that iPLA2beta has a role in phospholipid
      remodeling, signal transduction, cell proliferation, and apoptosis. We have found
      that pancreatic islets, beta-cells, and glucose-responsive insulinoma cells
      express an iPLA2beta that participates in glucose-stimulated insulin secretion
      but is not involved in membrane phospholipid remodeling. Additionally, recent
      studies reveal that iPLA2beta is involved in pathways that contribute to beta
      cell proliferation and apoptosis, and that various phospholipid-derived mediators
      are involved in these processes. Detailed characterization of the enzyme suggests
      that the beta-cells express multiple isoforms of iPLA2beta, and we hypothesize
      that these participate in different cellular functions.

PMID- 15573143
TI  - Vanadium and the cardiovascular functions.
AB  - Inorganic and organic compounds of vanadium have been shown to exhibit a large
      range of insulinomimetic effects in the cardiovascular system, including
      stimulation of glucose transporter 4 (GLUT-4) translocation and glucose transport
      in adult cardiomyocytes. Furthermore, administration of vanadium compounds
      improves cardiac performance and smooth muscle contractility, and modulates blood
      pressure in various models of hypertension and insulin resistance. Vanadium
      compounds are potent inhibitors of protein tyrosine phosphatases. As a result,
      they promote an increase in protein tyrosine phosphorylation of several key
      components of the insulin signaling pathway, leading to the upregulation of
      phosphatidylinositol 3-kinase and protein kinase B, two enzymes involved in
      mediating GLUT-4 trans location and glucose transport. In addition, vanadium has
      also been shown to activate p38 mitogen-activated protein kinase and increase
      Ca2+ levels in several cell types. The ability of vanadium compounds to activate
      these signaling events may be responsible for their ability to modulate
      cardiovascular functions.

PMID- 15573144
TI  - Cardiac transplantation and resistance artery myogenic tone.
AB  - Transplantation is an effective treatment for end-stage heart disease; however,
      most grafts eventually fail by progressive cardiac failure. Primarily, failure is
      ischemic due to the occlusive nature of transplant vascular disease (TVD). Early
      after transplantation and preceding TVD, alterations in coronary physiology such
      as reduced vascular myogenic tone occur. Resistance arteries possess an inherent
      ability to constrict in response to transmural pressure; this constrictive
      response (myogenic tone) is important in fluid homeostasis. Recent evidence
      suggests that a decline in myogenic tone leads to deficits in cardiac
      contractility. Factors that reduce myogenic tone in transplantation include
      constitutive nitric oxide synthase and inducible nitric oxide synthase catalyzed,
      NO-mediated vasodilation as well as deficits in arterial contractile function.
      Reduced myogenic tone in allograft resistance arteries increases coronary blood
      flow such that hydrostatic pressure surpasses oncotic pressure, causing cardiac
      interstitial edema. This generalized edema decreases ventricular compliance
      leading to heart failure during the course of acute immune rejection of the
      graft. Cyclosporine A treatment reduces immune mediated dysregulation of myogenic
      tone, resulting in reduced interstitial edema and improved cardiac function. In
      this review, we discuss aspects of TVD and myogenic tone signaling mechanisms and
      how aberrations in myogenic regulation of arterial tone contribute to functional
      changes observed in cardiac transplant.

PMID- 15573145
TI  - Potential role of N-myristoyltransferase in pathogenic conditions.
AB  - N-Myristoyltransferase (NMT) is the enzyme that catalyzes the covalent transfer
      of myristic acid to the N-terminal glycine residue of a protein substrate. In
      this review article, I summarize that NMT may have a potential role in cardiac
      muscle in the experimentally induced ischemia-reperfusion rat model and also in
      the streptozotoein-induced diabetic rat. Both the expression and activity of NMT
      were increased by ischemia-reperfusion. Immunohistochemical studies showed
      cytosolic localization of NMT in normal rat heart and predominant nuclear
      localization after ischemia followed by reperfusion. However, the localization of
      NMT is reversed by treatment with a calpain inhibitor (ALLM N-Ac-Leu-Leu
      methioninal). During ischemia-reperfusion, the degradation of c-Src, which is a
      substrate of NMT, was observed. These findings suggested that the Src signaling
      may be impaired in ischemia-reperfusion owing to the altered localization of NMT
      from cytoplasm to nucleus. Streptozotocin-induced diabetes (an animal model for
      insulin-dependent diabetes mellitus) resulted in a 2.0-fold increase in rat liver
      NMT activity as compared with control animals. In obese (fa/fa) Zucker rats (an
      animal model for non-insulin-dependent diabetes mellitus), there was an
      approximately 4.7-fold lower liver particulate NMT activity as compared with
      control lean rat livers. Administration of sodium orthovanadate to the diabetic
      rats normalized liver NMT activity. These results would indicate that rat liver
      particulate NMT activity appears to be inversely proportional to the level of
      plasma insulin, implicating insulin in the control of N-myristoylation. These are
      the first studies demonstrating the role of NMT in the pathogenesis of ischemia
      reperfusion and diabetes mellitus. These conditions remain an important area of
      investigation.

PMID- 15573146
TI  - "Vulnerable plaques"--ticking of the time bomb.
AB  - Atherosclerosis and its sequelae are one of the leading causes of morbidity and
      mortality, especially in the developed nations. Over the years, treatment
      protocols have changed with the changing understanding of the disease process.
      Inflammatory mechanisms have emerged as key players in the formation of the
      atherosclerotic plaque. For the majority of its life span, the plaque develops
      silently and only some exhibit overt clinical manifestations. The purpose of this
      review is to examine the inherent properties of some of these "vulnerable" or
      symptomatic plaques. Rupture of the plaque is related to the thickness of the
      fibrous cap overlying the necrotic lipid core. A thin cap is more likely to lead
      to rupture. Multiple factors broadly grouped as the "determinants of
      vulnerability" are responsible for directly or indirectly influencing the plaque
      dynamics. Apoptosis is considered an important underlying mechanism that
      contributes to plaque instability. Inflammatory reactions within the plaque
      trigger apoptosis by cell-cell contact and intra cellular death signaling. Once
      started, the apoptotic process affects all of the components that make up the
      plaque, including vascular smooth muscle cells, endothelial cells, and
      macrophages. Extensive research has identified many of the key cellular and
      molecular regulators that play a part in apoptosis within the atherosclerotic
      lesion. This information will help us to gain a better understanding of the
      underlying mechanisms at the cellular and molecular level and enable us to
      formulate better therapeutic strategies to combat this disease.

PMID- 15573147
TI  - Doxazosin-induced up-regulation of alpha 1A-adrenoceptor mRNA in the rat lower
      urinary tract.
AB  - Alpha1-adrenoceptor (AR) antagonists can provide effective treatment of symptoms
      caused by benign prostatic hyperplasia. However, their mechanisms of action have
      not been fully elucidated. We previously reported that chronic administration of
      doxazosin causes an up-regulation in the mRNA expression of all three alpha1-AR
      subtypes in the rat prostate. As alpha1-AR antagonists might also affect the
      properties of alpha1-ARs in the lower urinary tract, we examined the effects of
      doxazosin (2 or 4 mg/kg daily subcutaneously, supplemented with 4 mg/kg daily
      orally for 8 or 12 weeks) on alpha1-AR subtype mRNAs in the rat bladder dome,
      bladder base, and urethra using real-time reverse transcription PCR. Rats that
      received the highest doses of doxazosin had significantly heavier bladder base
      and prostatic urethra than controls. PCR data showed that all three alpha1-AR
      subtypes were expressed in all tissues studied. Doxazosin treatment caused an up
      regulation in the mRNA levels of alpha1A-AR in the rat bladder base and prostatic
      urethra, indicating that chronic doxazosin treatment may cause an alteration in
      the properties of alpha1A-AR subtype mRNA in these two areas. Furthermore, the
      heavier bladder base and prostatic urethra in the doxazosin-treated rats suggest
      that alpha1-AR antagonist treatment might also influence the growth process in
      these areas of the rat lower urinary tract.

PMID- 15573148
TI  - Increased efflux of glutathione conjugate in acutely diabetic cardiomyocytes.
AB  - In diabetes, cell death and resultant cardiomyopathy have been linked to
      oxidative stress and depletion of antioxidants like glutathione (GSH). Although
      the de novo synthesis and recycling of GSH have been extensively studied in the
      chronically diabetic heart, their contribution in modulating cardiac oxidative
      stress in acute diabetes has been largely ignored. Additionally, the possible
      contribution of cellular efflux in regulating GSH levels during diabetes is
      unknown. We used streptozotocin to make Wistar rats acutely diabetic and after 4
      days examined the different processes that regulate cardiac GSH. Reduction in
      myocyte GSH in diabetic rats was accompanied by increased oxidative stress,
      excessive reactive oxygen species, and an elevated apoptotic cell death. The
      effect on GSH was not associated with any change in either synthesis or
      recycling, as both gamma-glutamylcysteine synthetase gene expression (responsible
      for bio syn thesis) and glutathione reductase activity (involved with GSH
      recycling) remained unchanged. However, gene expression of multidrug resistance
      protein 1, a transporter implicated in effluxing GSH during oxidative stress, was
      elevated. GSH conjugate efflux mediated by multidrug resistance protein 1 also
      increased in diabetic cardiomyocytes, an effect that was blocked using MK-571, a
      specific inhibitor of this transporter. As MK-571 also decreased oxidative stress
      in diabetic cardiomyocytes, an important role can be proposed for this
      transporter in GSH and reactive oxygen species homeostasis in the acutely
      diabetic heart.

PMID- 15573149
TI  - Effective control of glycemic status and toxicity in Zucker diabetic fatty rats
      with an orally administered vanadate compound.
AB  - A novel black tea decoction containing vanadate has successfully replaced insulin
      in a rat model of insulin-dependent diabetes but is untested in non-insulin
      dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg
      sodium orthovanadate was administered by oral gavage to two groups of Zucker
      diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of
      sodium orthovanadate to two others. In the latter group receiving the 30-mg dose,
      vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV
      treated rats had no incidence of diarrhea and no deaths. Symptoms were more
      severe in both groups with higher vanadate doses, so these were discontinued.
      After approximately 16 weeks, the level of vanadium in plasma and tissue extracts
      was negligible in a further group of untreated rats but highly elevated after
      vanadate treatment. Vanadium levels were not significantly different between the
      TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle.
      Over the 115 days of the study, blood glucose levels increased from approximately
      17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10
      mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in
      control (nondiabetic, untreated), TV-treated and untreated diabetic rats,
      respectively. Rats required treatment with TV for only approximately 50% of the
      days in the study. Increase in body mass during the study was significantly lower
      in untreated diabetic rats (despite higher food intake) than the other groups.
      Body mass gain and food intake were normal in TV-treated rats. Water intake was
      28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and
      52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate
      aminotransferase levels were significantly depressed in untreated diabetic rats,
      and TV treatment normalized this. Our results demonstrate that a novel oral
      therapy containing black tea and vanadate possesses a striking capacity to
      regulate glucose and attenuates complications in a rat model of type II diabetes.

PMID- 15573150
TI  - Differential participation of protein kinase C and Rho kinase in alpha 1
      adrenoceptor mediated contraction in rat arteries.
AB  - The major functional alpha1-adrenoceptor in the rat aorta is of the
      alpha1Dsubtype and that in the caudal artery is of the alpha1A subtype. In the
      present study, the participation of protein kinase C (PKC) and Rho kinase (RhoK)
      in contractile responses to stimulation of the alpha1-adrenoceptors in these two
      arteries was investigated. Both the PKC inhibitor Ro-318220 and the RhoK
      inhibitor Y-27632 significantly blocked contractile responses of the aorta to
      phenylephrine (PE) and the selective alpha1A-adrenoceptor agonist A61603. When
      used in combination, the inhibitors had an additive blocking effect. In the
      caudal artery, Y-27632 but not Ro-318220 inhibited contractile responses to PE
      and A61603, and, in combination, the antagonism produced was no greater than that
      by Y-27632 alone. Contractile responses to direct activation of PKC with phorbol
      12,13-dibutyrate were much smaller and levels of CPI-17 (PKC-activated protein
      phosphatase inhibitor of 17 kDa) were much lower in the caudal artery than the
      aorta. The results suggest that both PKC and RhoK contribute independently to
      contractile responses to stimulation of alpha1D-adrenoceptors in the aorta.
      However, RhoK, but not PKC, participates in contractile responses to stimulation
      of alpha1A-adrenoceptors in the caudal artery. This difference may largely be due
      to differences between the two arteries in the extent to which PKC participates
      in contraction.

PMID- 15573151
TI  - Altered inotropic reactivity in diabetic rabbit right ventricular myocardium.
AB  - Alloxan monohydrate was used to induce diabetes in rabbits, which were maintained
      for a 3-month period with or without daily insulin replacement along with age
      matched controls. Isolated right ventricular myocardial strips were used to
      generate dose-response curves to isoproterenol, forskolin, and Bay K 8644. Basal
      developed force was significantly elevated in diabetic ventricular strips. While
      isoproterenol acted as a full inotropic agonist, diabetic preparations revealed a
      consistent but insignificant decrease in the maximum developed force. While both
      sensitivity to isoproterenol and beta-adrenoceptor density were decreased in
      preparations from diabetic rabbits, there was no associated increase in
      circulating plasma catecholamines. In contrast, forskolin and Bay K 8644 were
      partial agonists in control preparations but full inotropic agonists in diabetic
      preparations, demonstrating significant increases in maximum developed force.
      This hyperresponsiveness was not associated with altered calcium channel density.
      Finally, insulin replacement reduced or prevented all diabetic-related changes.
      These data indicate that the hyperresponsiveness to forskolin and Bay K 8644
      represents an altered utilization of intracellular calcium in the diabetic
      rabbit, converting them into full agonists similar to isoproterenol. The decrease
      in sensitivity to isoproterenol correlated with a decrease in beta-adrenoceptor
      density but not elevated circulating catecholamines as previously observed in
      diabetic rats.

PMID- 15573152
TI  - Differential effects of sodium tungstate and vanadyl sulfate on vascular
      responsiveness to vasoactive agents and insulin sensitivity in fructose-fed rats.
AB  - High fructose feeding induces insulin resistance, impaired glucose tolerance, and
      hypertension in rats and mimics most of the features of the metabolic syndrome X.
      The effects of a 6-week treatment with the transition metals administered in
      drinking water, vanadium (VOSO4.5H2O, 0.75 mg/mL) or tungsten (Na2O4W, 2 g/mL),
      were investigated on the reactivity to norepinephrine (NEPI) or acetylcholine
      (ACh) of thoracic aorta rings isolated from fructose (60%) or standard chow fed
      rats. Maximal effect (Emax) and pD2 (-log EC50) values were determined in each
      case in the presence or absence of endothelium, while the degree of insulin
      resistance was determined using the euglycemic hyper insulinemic glucose clamp
      technique. Aortic segments isolated from 6-week fructose-fed animals were
      characterized by NEPI hyperresponsiveness (increase in Emax) and endothelium
      dependent NEPI supersensitivity (increase in pD2) without any change in the
      reactivity to ACh. Vanadium or tungsten administered in fructose-fed animals
      prevented both hypertension and NEPI hyperresponsiveness, while vanadium, but not
      tungsten, reduced NEPI supersensitivity. Vanadium, but not tungsten, increased
      the relaxing activity of ACh, both in control and fructose-fed animals. Insulin
      resistance associated with high fructose feeding was reversed by vanadium but not
      by tungsten treatment. The differential effects of the two transition metals on
      vascular responsiveness to NEPI or ACh may be explained by their differential
      effects on insulin sensitivity.

PMID- 15573153
TI  - Application of high-dose propofol during ischemia improves postischemic function
      of rat hearts: effects on tissue antioxidant capacity.
AB  - Previous studies have shown that reactive oxygen species mediated lipid
      peroxidation in patients undergoing cardiac surgery occurs primarily during
      cardiopulmonary bypass. We examined whether application of a high concentration
      of propofol during ischemia could effectively enhance postischemic myocardial
      functional recovery in the setting of global ischemia and reperfusion in an
      isolated heart preparation. Hearts were subjected to 40 min of global ischemia
      followed by 90 min of reperfusion. During ischemia, propofol (12 microg/mL in
      saline) was perfused through the aorta at 60 microL/min. We found that
      application of high-concentration propofol during ischemia combined with low
      concentration propofol (1.2 microg/mL) administered before ischemia and during
      reperfusion significantly improved postischemic myocardial functional recovery
      without depressing cardiac mechanics before ischemia, as is seen when high
      concentration propofol was applied prior to ischemia and during reperfusion. The
      functional enhancement is associated with increased heart tissue antioxidant
      capacity and reduced lipid peroxidation. We conclude that high-concentration
      propofol application during ischemia could be a potential therapeutic and
      anesthetic strategy for patients with preexisting myocardial dysfunction.

PMID- 15573154
TI  - Effects of valproic acid on cardiac metabolism.
AB  - We investigated whether the antiepileptic valproic acid (VPA) might interfere
      with oxidative metabolism in heart, as it does in liver. We administered VPA to
      working rat hearts perfused with radiolabeled carbohydrate and fatty acid fuels.
      Measurements included oxidation rates of (i) glucose, pyruvate, or lactate in the
      presence of palmitate and (ii) palmitate, octanoate, or butyrate in the presence
      of glucose. Oxidation rates were quantified as the rate of appearance of 14CO2 or
      3H2O from 14C- or 3H-labeled substrates. In hearts perfused with palmitate, VPA
      (1 mmol/L) strongly inhibited the oxidation of pyruvate and lactate but slightly
      stimulated the oxidation of glucose. VPA also inhibited lactate or pyruvate
      uptake into erythrocytes in vitro. In hearts perfused with glucose, VPA strongly
      inhibited the oxidation of palmitate and octanoate but had no effect on butyrate
      oxidation. The absence of valproate CoA ligase activity in cell-free homogenates
      indicated that the inhibition of fatty acid oxidation by VPA did not require
      prior activation to valproyl-CoA. The results are consistent with the hypothesis
      that VPA selectively interferes with myocardial fuel oxidation by mechanisms that
      are independent of conversion to the CoA thioester.

PMID- 15573155
TI  - Depression and SSRI antidepressants in children and youth.

PMID- 15573156
TI  - Bio-mimicking galactose oxidase and hemocyanin, two dioxygen-processing copper
      proteins.
AB  - The modelling of the active sites of metalloproteins is one of the most
      challenging tasks in bio-inorganic chemistry. Copper proteins form part of this
      stimulating field of research as copper enzymes are mainly involved in oxidation
      bio-reactions. Thus, the understanding of the structure-function relationship of
      their active sites will allow the design of effective and environmental friendly
      oxidation catalysts. This perspective illustrates some outstanding structural and
      functional synthetic models of the active site of copper proteins, with special
      attention given to models of galactose oxidase and hemocyanin.

PMID- 15573157
TI  - Synthesis of the new, weakly coordinating anions [RB(C6F5)3]- (R = CH2Me, CHMe2,
      CH2CMe3); utilization of [HNMe2Ph][Me3CCH2B(C6F5)3] to activate zirconocene
      catalysts for propylene polymerization.
AB  - The compound [HNMe2Ph][NpB(C6F5)3](Np =(CH3)3CCH2) reacts with
      dimethylzirconocenes to give active propylene polymerization catalysts which are
      significantly more active and give higher molecular weight polypropylene than do
      the catalysts obtained using B(C6F5)3; the [NpB(C6F5)3]- anion is for steric
      reasons more weakly coordinating than is [MeB(C6F5)3]-.

PMID- 15573158
TI  - Nucleophilic substitution on a Ru-coordinated Cp ring by a carborane anion.
AB  - The Cp ring in [RuCl(Cp)(PPh3)2] undergoes an apparent nucleophilic attack by the
      carbanion carb- (Hcarb = 2-Me-1,2-dicarba-closo-dodecaborane), to give an H-/carb
      exchange process, which is favoured by coordination of the hydride to the
      ruthenium centre.

PMID- 15573159
TI  - Semi-vacant Wells-Dawson anions. Synthesis of tri-tungsten-vacant derivatives and
      crystallographic studies of [alphabetabetaalpha
      (Cu(II)OH2)2(Cu(II))2(AsW15(OH2)3(OH)O52)2]12-.
AB  - The tri-tungsten-vacant polyoxometalate, [alpha-AsW15(OH)4O52]13-, derived from
      the semi-vacant Wells-Dawson complex [alpha-AsW18(OH)4O58]7-, reacts with the
      late-transition metal cations, Cu(II) or Zn(II), to form sandwich-type species;
      the X-ray crystal structure of [alphabetabetaalpha]
      (Cu(II)OH2)2(Cu(II))2(AsW15(OH2)3(OH)O52)2]12-, prepared by the acidification of
      [alphabetabetaalpha]-(Cu(II)OH2)2(Cu(II))2(AsW15(OH)4O52)2]18-, reveals that the
      missing heteroatoms are distal to the central Cu4 unit and the vertices of the
      vacant tetrahedron are occupied by one OH- and three OH2 groups.

PMID- 15573160
TI  - Statistical mechanical approach to competitive binding of metal ions to multi
      center receptors.
AB  - A microscopic site binding model to treat binding of several metal ions to multi
      center receptors is proposed. The model introduces the appropriate
      parameterization in terms of microscopic complexation constants and metal-metal
      pair interaction energies. The model is solved with statistical mechanical
      techniques, including direct enumeration or transfer matrices. We obtain
      microscopic and macroscopic complexation constants, microstate probabilities, and
      binding isotherms for chain-like receptors, including the long-chain limit.
      Various examples to illustrate the usefulness of the model are given.

PMID- 15573161
TI  - C-F or C-H bond activation and C-C coupling reactions of fluorinated pyridines at
      rhodium: synthesis, structure and reactivity of a variety of tetrafluoropyridyl
      complexes.
AB  - Reactions of [RhH(PEt3)3] (1) or [RhH(PEt3)4] (2) with pentafluoropyridine or
      2,3,5,6-tetrafluoropyridine afford the activation product [Rh(4-C5NF4)(PEt3)3]
      (3). Treatment of 3 with CO, 13CO or CNtBu effects the formation of trans-[Rh(4
      C5NF4)(CO)(PEt3)2] (4a), trans-[Rh(4-C5NF4)(13CO)(PEt3)2] (4b) and trans-[Rh(4
      C5NF4)(CNtBu)(PEt3)2] (5). The rhodium(III) compounds trans-[RhI(CH3)(4
      C5NF4)(PEt3)2] (6a) and trans-[RhI(13CH3)(4-C5NF4)(PEt3)2] (6b) are accessible on
      reaction of 3 with CH3I or 13CH3I. In the presence of CO or 13CO these complexes
      convert into trans-[RhI(CH3)(4-C5NF4)(CO)(PEt3)2] (7a), trans-[RhI(13CH3)(4
      C5NF4)(CO)(PEt3)2] (7b) and trans-[RhI(13CH3)(4-C5NF4)(13CO)(PEt3)2] (7c). The
      trans arrangement of the carbonyl and methyl ligand in 7a-7c has been confirmed
      by the 13C-13C coupling constant in the 13C NMR spectrum of 7c. A reaction of 4a
      or 4b with CH3I or 13CH3I yields the acyl compounds trans-[RhI(COCH3)(4
      C5NF4)(PEt3)2] (8a) and trans-[RhI(13CO13CH3)(4-C5NF4)(PEt3)2] (8b),
      respectively. Complex 8a slowly reacts with more CH3I to give
      [PEt3Me][Rh(I)2(COCH3)(4-C5NF4)(PEt3)](9). On heating a solution of 7a, the
      complex trans-[RhI(CO)(PEt3)2] (10) and the C-C coupled product 4
      methyltetrafluoropyridine (11) have been obtained. Complex 8a also forms 10 at
      elevated temperatures in the presence of CO together with the new ketone 4
      acetyltetrafluoropyridine (12). The structures of the complexes 3, 4a, 5, 6a, 8a
      and 9 have been determined by X-ray crystallography. 19F-1H HMQC NMR solution
      spectra of 6a and 8a reveal a close contact of the methyl groups in the phosphine
      to the methyl or acyl ligand bound at rhodium.

PMID- 15573162
TI  - Bulk material vs. single crystal: powder diffraction to the rescue.
AB  - The crystal structure of bulk microcrystalline material obtained by interaction
      of two rigid building blocks, namely dirhodium(ii) tetra(trifluoroacetate),
      [Rh2(O2CCF3)4], and bis(4'-pyridyl)diphenylsilane, (C6H5)2Si(C5H4N)2, has been
      solved ab initio using X-ray powder diffraction data. The title product of the 1
      [ratio] 1 composition, [Rh2(O2CCF3)4.(mu2-(C6H5)2Si(C5H4N)2)], is a one
      dimensional zigzag polymer built on axial Rh...N interactions averaged at 2.16 A.
      Its structural characterization complements the previously reported product of
      the 2:1 composition obtained from the same reaction, namely {[Rh2(O2CCF3)4]2.(mu4
      (C6H5)2Si(C5H4N)2)}. The latter has a 2D layered network revealed by the single
      crystal diffraction study. A combination of powder and single crystal X-ray
      techniques is shown to be methodologically important and complementary for
      understanding of product assembling in the system.

PMID- 15573163
TI  - Diastereoisomeric dinuclear ruthenium complexes of 2,5-di(2-pyridyl)thiazolo[5,4
      d]thiazole.
AB  - The first metal complexes of 2,5-di(2-pyridyl)thiazolo[5,4-d]thiazole (5) are
      described. X-Ray crystal structures are reported for the free ligand 5, a
      dinuclear copper complex 6 and the two diastereoisomers, 7meso and 7rac, of the
      dinuclear bis(2,2'-bipyridine)ruthenium complex. The two diastereoisomers of 7
      and the 4,4'-dimethyl-2,2'-bipyridine analogue 8 are readily separated by cation
      exchange chromatography. 1H NMR and visible absorption spectra and
      electrochemical data for the four dinuclear ruthenium complexes reveal that these
      have relatively small HOMO-LUMO energy gaps and exhibit relatively weak metal
      metal interactions.

PMID- 15573164
TI  - Ruthenium bipyridyl compounds with two terminal alkynyl ligands.
AB  - Compounds of the form Ru(X2bipy)(PPh3)2(-C triple bond CC6H4NO2-p)2(X2bipy = 4,4'
      X(2)-2,2'-bipyridine, X = Me 3a, Br 3b, I 3c) have been synthesised from the mono
      alkynyl precursors Ru(X2bipy)(PPh3)2(-C triple bond CC6H4NO2-p)Cl (X = Me 2a, Br
      2b, I 2c); the former are the first ruthenium bis-alkynyl compounds that also
      contain a bipyridyl ligand. Spectroelectrochemical investigation of 3a shows that
      the metal is readily oxidised to form the ruthenium(III) compound 3a+, and will
      also undergo a single-electron reduction at each nitro group to form 3a2-. ESR
      and UV/visible spectra of these redox congeners are presented. We also report the
      synthesis of [Ru(Me2bipy)(PPh3)2(-C triple bond CBut)(N triple bond N)][PF6]
      during the attempted synthesis of Ru(Me2bipy)(PPh3)2(-C triple bond CBut)2, and
      report its X-ray crystal structure and IR spectrum. X-Ray crystal structures of
      3b and 3c(as two different solvates) are presented, and the nature of the
      intermolecular interactions seen therein is discussed. Z-Scan measurements on
      Ru(Me2bipy)(PPh3)2(-C triple bond CR)Cl (R = C6H4NO2-p2a, But, Ph, C6H4Me) are
      also reported, and show that Ru(Me2bipy)(PPh3)2(-C triple bond CR)Cl (R = C6H4NO2
      p2a, Ph) exhibit moderate third-order non-linearities.

PMID- 15573165
TI  - Synthesis and crystal structure of tetra- and hexanuclear uranium(IV) complexes
      with hexadentate compartmental Schiff-base ligands.
AB  - Treatment of UCl4 with the hexadentate Schiff bases H2Li in thf gave the expected
      [ULiCl2(thf)] complexes [H2Li=N,N'-bis(3-methoxysalicylidene)-R and R = 2,2
      dimethyl-1,3-propanediamine (i= 1), R = 1,3-propanediamine (i= 2), R = 2-amino
      benzylamine (i= 3), R = 2-methyl-1,2-propanediamine (i= 4), R = 1,2
      phenylenediamine (i= 5)]. The crystal structure of [UL4Cl2(thf)] (4) shows the
      metal in a quite perfect pentagonal bipyramidal configuration, with the two Cl
      atoms in apical positions. Reaction of UCl4 with H4Li in pyridine did not afford
      the mononuclear products [U(H2Li)Cl2(py)x] but gave instead polynuclear complexes
      [H4Li=N,N'-bis(3-hydroxysalicylidene)-R and R = 1,3-propanediamine (i= 6), R = 2
      amino-benzylamine (i= 7) or R = 2-methyl-1,2-propanediamine (i= 8)]. In the
      presence of H4L6 and H4L7 in pyridine, UCl4 was transformed in a serendipitous
      and reproducible manner into the tetranuclear U(iv) complexes
      [Hpy]2[U4(L6)2(H2L6)2Cl6] (6a) and
      [Hpy]2[U4(L7)2(H2L7)2Cl6][U4(L7)2(H2L7)2Cl4(py)2] (7), respectively. Treatment of
      UCl4 with [Zn(H2L6)] led to the formation of the neutral compound
      [U4(L6)2(H2L6)2Cl4(py)2] (6b). The hexanuclear complex [Hpy]2[U6(L8)4Cl10(py)4]
      (8) was obtained by reaction of UCl4 and H4L8. The centrosymmetric crystal
      structures of 6a.2HpyCl.2py, 6b.6py, 7.16py and 8.6py illustrate the potential of
      Schiff bases as associating ligands for the design of polynuclear assemblies.

PMID- 15573166
TI  - A stepwise degradation of sterically hindered CpCo-cyclobutadiene complexes.
AB  - Sterically hindered CpCo stabilized cyclobutadiene complexes 4 were oxidized by
      ceric ammonium nitrate to yield the dinitratocobalt complexes 5. The thermolysis
      of 5a and the reaction of 5a with tert-butyl isocyanide as well as NaBH4 is
      reported.

PMID- 15573167
TI  - Interactions of Ni(II) and Cu(II) ions with the hydrolysis products of the C
      terminal -ESHH- motif of histone H2A model peptides. Association of the stability
      of the complexes formed with the cleavage of the -E-S- bond.
AB  - We studied the interactions of Ni(II) and Cu(II) ions with the synthetic
      tetrapeptides SHHK- and SAHK-, which were blocked by amidation making them more
      realistic models of the hydrolysis peptidic products of the hexapeptides models
      of H2A histone. A combination of potentiometric and spectroscopic techniques
      (UV/Vis, CD, NMR and EPR) suggested that at pH > 7 both tetrapeptides coordinated
      equatorially through the imidazole ring of His in position 3, the N-terminal
      amino group and the two amide nitrogens existing between these groups {NH2, 2N-,
      NIm} forming 4N square-planar complexes. While in the case of the CuH(-1)L
      complex with SHHK- a possible axial coordination of the imidazole ring of His in
      position 2 was suggested, in the case of the analogous NiH(-1)L complex a
      completely different interaction of the same ring with metal ions was observed.
      As expected these complexes have the same structures with the hydrolysis products
      produced from the Ni(II)- or Cu(II)-assisted hydrolysis of previously studied
      hexapeptide models of the C-terminal of histone H2A, due to their predominance at
      pH > 7.4. In addition, the competition plots presented herein showed that the
      synthetic tetrapeptides SHHK- and SAHK- have higher affinity towards Ni(II) and
      Cu(II) ions than the previously studied hexapeptides, suggesting that metal ions
      remain bound to the peptidic products during the hydrolysis cleavage. Thus, it
      can be concluded that the stability of Ni(II) or Cu(II) complexes with the
      synthetic tetrapeptides and consequently with the real hydrolysis peptidic
      products is the driving force of the hydrolysis reaction of H2A histone blocked
      hexapeptide models, presented in previous studies.

PMID- 15573168
TI  - End-to-end single cyanato and thiocyanato bridged Cu(II) polymers with a new
      tridentate Schiff base ligand: crystal structure and magnetic properties.
AB  - A new tridentate Schiff base ligand HL (L = C14H19N2O), derived from the
      condensation of benzoylacetone and 2-dimethylaminoethylamine in a 1:1 ratio,
      reacts with copper(ii) acetate and cyanate, thiocyanate or azide, to give rise to
      several end-to-end polymeric complexes of formulae [CuL(mu(1,3)-NCO)]n 1,
      [CuL(mu(1,3)-NCS)]n 2 and the complex 3 has two crystallographically independent
      units of formula [CuL(N3)] in the asymmetric unit cell. Complex 3 exists in
      dimeric form rather than as a polymeric chain. Compound 1 is the first report of
      a singly end-to-end cyanate bridged polymeric chain of Cu(II) with a Schiff base
      as a co-ligand. There are many examples of double NCS bridged polymeric chains,
      but fewer singly bridged ones such as compound 2. We have characterized these
      complexes by analytical, spectroscopic, structural and variable temperature
      magnetic susceptibility measurements. The coordination geometry around the Cu(II)
      centers is distorted square pyramidal for 1 and 2 and square planar for complex
      3. The magnetic susceptibility data show slight antiferromagnetic coupling for
      the polymers having J values -0.19 and -0.57 cm(-1) for complexes 1 and 2
      respectively. The low values of J are consistent with the equatorial-axial
      disposition of the bridges in the polymers.

PMID- 15573169
TI  - Proton induced P-H and Mo-H bond activation at the phosphide bridged dimolybdenum
      complexes [Mo2Cp2(mu-H)(mu-PHR)(CO)4](R = Cy, 2,4,6-C6H2R'3; R'= H, Me, tBu).
AB  - The new hydride complexes [Mo2Cp2(mu-H)(mu-PHR)(CO)4] having bulky substituents
      (R = 2,4,6-C(6)H2tBu3= Mes*, R = 2,4,6-C6H2Me3= Mes) have been prepared in good
      yield by addition of Li[PHR] to the triply bonded [Mo2Cp2(CO)4] and further
      protonation of the resulting anionic phosphide complex [Mo2Cp2(mu-PHR)(CO)4]-.
      Protonation of the Mes* compound with either [H(OEt2)2][B{3,5-C6H3(CF3)2}4] or
      HBF4.OEt2 gives the cationic phosphinidene complex [Mo2Cp2(mu-H)(mu-PMes*)(CO)4]+
      in high yield. In contrast, protonation of the analogous hydride compounds with
      Mes or Cy substituents on phosphorus give the corresponding unsaturated
      tetracarbonyls [Mo2Cp2(mu-PHR)(CO)4]+, which are unstable at room temperature and
      display a cis geometry. Decomposition of the latter give the electron-precise
      pentacarbonyls [Mo2Cp2(mu-PHR)(mu-CO)(CO)4]+, also displaying a cis arrangement
      of the metal fragments. In the presence of BF4- as external anion, fluoride
      abstraction competes with carbonylation to yield the neutral fluorophosphide
      hydrides [Mo2Cp2(mu-H)(mu-PFR)(CO)4]. Similar results were obtained in the
      protonation reactions of the hydride compounds having a Ph substituent on
      phosphorus. In that case, using HCl as protonation reagent gave the chloro
      complex [Mo2ClCp2(mu-PHPh)(CO)4] in good yield. The structures and dynamic
      behaviour of the new compounds are analyzed on the basis of solution IR and 1H,
      31P, 19F and 13C NMR data as well as the X-ray studies carried out on [Mo2Cp2(mu
      H)(mu-PHMes)(CO)4](cis isomer), [Mo2Cp2(mu-H)(mu-PFMes)(CO)4](trans isomer),
      [Mo2Cp2(mu-PHCy)(mu-CO)(CO)4](BF4) and [Mo2ClCp2(mu-PHPh)(CO)4].

PMID- 15573170
TI  - Synthetic analogue approach for the functional domains of copper(II) bleomycins
      and its DNA cleavage activity.
AB  - The dicopper(II) complex [Cu2(R'SSR)2(SO4)2] (1), where R'SSR is a Schiff base,
      has been prepared from the reaction of CuSO4.5H2O with the Schiff base N,N'-1,1'
      dithiobis(ethylenesalicylaldimine)(H2RSSR) and structurally characterized by X
      ray crystallography. The crystal structure of 1 shows two {Cu(R'SSR)}2+ units
      linked by two sulfate ligands each showing a eta3,mu2-binding mode. The Cu...Cu
      distance is 4.562(2)A with each copper having a square pyramidal (4 + 1) CuNO4
      coordination geometry. The monoanionic Schiff base R'SSR has a pendant cationic
      amine -SCH2CH2NH3+ group which is presumably formed from the hydrolysis of one
      imine bond of H2RSSR. Complex 1 models the N- and C-terminus domains of
      bleomycins. The metal centers in 1 are essentially magnetically non-interacting
      giving a -2J value of 3 cm(-1) with the singlet as the ground state. Using
      complex 1 as a precursor, ternary copper(II) complexes [Cu(R'SSR)B(SO4)] (2-4)-
      are prepared, characterized and their DNA binding and cleavage properties studied
      (B: kanamycin A, 2; 2,2'-bipyridine, 3; 1,10-phenanthroline, 4). IR spectral data
      suggest a square pyramidal (4 + 1) geometry for the one-electron paramagnetic
      ternary complexes with the sulfate bound to copper. The complexes are non
      conducting in DMF but show conductivity in aqueous medium due to dissociation of
      the sulfate ligand. They bind to calf thymus DNA in the minor groove giving the
      relative order: 4 > 2 > 1 approximately 3 (Kapp= 5.4 x 10(5) M(-1) for 4). The
      precursor complex 1 does not show any apparent chemical nuclease activity when
      treated with supercoiled (SC) DNA in the presence of 3-mercaptopropionic acid
      (MPA). The kanamycin A and phen adducts as such or generated under in situ
      reaction conditions using 1 nd the ligand display efficient chemical nuclease
      activity in the presence of MPA, while the bpy species shows poor cleavage
      activity. The ternary kanamycin A complex presents the first synthetic model for
      three functional domains of bleomycins.

PMID- 15573171
TI  - Investigating the effect of hydrogen bonding environments in amide cleavage
      reactions at zinc(II) complexes with intramolecular amide oxygen co-ordination.
AB  - Amide oxygen co-ordination to a zinc(II) ion around a hydrogen bonding
      microenvironment is a common structural/functional feature of metalloproteases.
      We report two strategies to position hydrogen bonding groups in the proximity of
      a zinc(II)-bound amide oxygen, and we investigate their effect on the stability
      of the amide group. Polydentate tripodal ligands (6-R1-2-pyridylmethyl)-R2 (R1=
      NHCOtBu, R2= N(CH2-py-6-X)2 X = H L1, X = NH2, H L2, X = NH2 L3) form [(L)Zn]2+
      cations (L =L1, 1; L2, 2; L3, 3) with intramolecular amide oxygen co-ordination
      (1-3), and intramolecular N-H...O=C(amide) hydrogen bonding (2, 3) rigidly fixed
      by the ligand framework. 1-3 undergo cleavage of the tert-butyl amide upon
      addition of Me4NOH.5H2O (1 equiv.) in methanol at 50(1) degrees C. Under these
      conditions the half-life, t(1/2), of the amide bond is 0.4 h for 1, 9 h for 2 and
      320 h for 3. Mononuclear zinc(II) complexes of (6-NHCOtBu-2-pyridylmethyl)-R2(R2=
      N(CH2CH2)2S) L4 and chelating N2 ligands without hydrogen bonding groups (1,10
      phenanthroline L5, 2-(aminomethyl)pyridine L6) as control compounds, and with an
      amino hydrogen bonding group (6-amino-2-(aminomethyl)pyridine L7) have been
      synthesised. Amide cleavage is in this case faster at the zinc(II) complex with
      the amino hydrogen bonding group. Thus, hydrogen bonding environments can both
      accelerate and slow down amide bond cleavage reactions at zinc(II) sites.
      Importantly, the magnitude of the effect exerted by the hydrogen bonding
      environments was found to be significant; 800-fold rate difference. This result
      highlights the importance of hydrogen bonding environments around metal centres
      in amide cleavage reactions, which may be relevant to the chemistry of natural
      metalloproteases and applicable to the design of more efficient artificial
      protein cleaving agents.

PMID- 15573172
TI  - Synthesis and structures of beta-diketiminatotin(II) halides, an amide and of
      Sn(=E)[{N(R)C(Ph)}2CH](NR2) (E = S or Se, R = SiMe3).
AB  - Treatment of [Li(L1)]2 (1) or K(L2) (2) with SnX2 in Et2O yielded the
      heteroleptic beta-diketiminatotin(II) halides Sn(L1)Cl (3a), Sn(L1)Br (3b) or
      Sn(L2)Cl (4), even when an excess of the alkali metal beta-diketiminate was used
      [L1={N(R)C(Ph)}2CH, L2={N(R)C(Ph)CHC(But)N(R)}, R = SiMe3]. From and half an
      equivalent each of SnCl2.2H2O and SnCl2, or one equivalent of SnCl2.2H2O, the
      product was Sn(L3)Cl (5) or Sn(L4)Cl (6), in which one or both of the N-R bonds
      of L1 had been hydrolytically cleaved; the compound Sn(L5)Cl (7) was similarly
      obtained from and an equivalent portion of SnCl2.2H2O
      [L3={N(R)C(Ph)CHC(But)N(H)}, L4={N(H)C(Ph)CHC(But)N(H)} and L5={N(H)C(Ph)}2CH].
      The halide exchange between 3a and 3b, studied by two-dimensional (119)Sn{1H}-NMR
      spectroscopy, is attributed to implicate a (mu-Cl)(mu-Br)-dimeric intermediate or
      transition state. The 13C{1H}-NMR spectra of or showed two distinct resonances
      for each group, which coalesced on heating, corresponding to DeltaG(338 K)= 69.4
      (3a) or 72.8 (3b) kJ mol(-1). The chloride ligand of was readily displaced by
      treatment with NaNR2, CF3SO3H or CH2(COPh)2, yielding Sn(L1)X [X = NR2 (8),
      O3SCF3 (9) or {OC(Ph)}2CH (10)]. Oxidative addition of sulfur or selenium to gave
      the tin(IV) terminal chalcogenides Sn(E)(L1)(NR2)[E = S (11) or Se (12)]. The X
      ray structures of the cocrystal of 3a/3b and of the crystalline compounds 5, 6,
      8, 11 and are presented, as well as multinuclear NMR spectra of each of the new
      compounds.

PMID- 15573173
TI  - Water-soluble hydroxyalkylated phosphines: examples of their differing behaviour
      toward ruthenium and rhodium.
AB  - The reaction of P(CH2OH)3 (I) and P(C6H5)(CH2OH)2 (II) with RuCl3 in methanol
      eliminates two equivalents of formaldehyde to yield the mixed tertiary and
      secondary phosphine complexes all-trans-[RuCl2(P(CH2OH)3)2(P(CH2OH)2H)2] (1) and
      [RuCl2(P(C6H5)(CH2OH)2)2(P(C6H5)(CH2OH)H)2] (2), respectively. There is a high
      degree of hydrogen-bonding interactions between the hydroxymethyl groups in 1 and
      2, although the phenyl groups of the latter reduce the extent of the network
      compared to 1. The generation of these mixed secondary and tertiary phosphine
      complexes is unprecedented. Under the same reaction conditions, the
      tris(hydroxypropyl)phosphine III formed no ruthenium complex. The reaction of
      P(CH2OH)3, P(C6H5)(CH2OH)2 and P{(CH2)3OH}3 with [RhCl(1,5-cod)]2 in an
      aqueous/dichloromethane biphasic medium yielded [RhH2(P(CH2OH)3)4]+ (3),
      [RhH2(P(C6H5)(CH2OH)2)4]+ (4) and [Rh(P(C6H5)(CH2OH)2)4]+ (5) and
      [Rh(P{(CH2)3OH}3)4]+ (6), respectively. Treating 5 with dihydrogen rapidly gave
      4. The hydroxypropyl compound 6 formed the corresponding dihydride much more
      slowly in aqueous solution, although [RhH2(P{(CH2)3OH}3)4]+ (7) was readily
      formed by reaction with dihydrogen. Two separate reaction pathways are therefore
      involved; for P(CH2OH)3 and to a lesser extent P(C6H5)(CH2OH)2, the hydride
      source in the product is likely to be the aqueous solvent or the hydroxyl
      protons, whilst for P{(CH2)3OH}3 an oxidative addition of H2 is favoured. The
      protic nature of and was illustrated by the H-D exchange observed in d2-water.
      Dihydrides 3 and 4 reacted with carbon monoxide to yield the dicarbonyl cations
      [Rh(CO)2(P(CH2OH)3)3]+ (8) and [Rh(CO)2(P(C6H5)(CH2OH)2)3]+ (9). The analogous
      experiment with [RhH2(P{(CH2)3OH}3)4]+ resulted in phosphine exchange, although
      our experimental evidence points to the possibility of more than one fluxional
      process in solution.

PMID- 15573174
TI  - Transfusion transmitted virus and autoimmune hepatitis. Is there any association?

PMID- 15573175
TI  - Role of tuberculosis laboratories in Saudi Arabia. A call to implement
      standardized procedures.
AB  - There is no doubt that the laboratory is the backbone for the diagnosis of
      tuberculosis (TB). Only through testing in the laboratory can the physician
      confirm suspicion of TB despite any previous clinical and x-ray findings. Recent
      visits to several laboratories in the Kingdom of Saudi Arabia showed that some
      need considerable improvement. Unless there are standardized procedures to
      diagnose TB, and safety measures are implemented in all laboratories, it will be
      impossible to diagnose accurately and control TB. The laboratories should be
      redesigned to conform to international TB Diagnostic Centers, with well trained
      staff and proper safety procedures.

PMID- 15573176
TI  - The natural history and the national pre-marital screening program in Saudi
      Arabia.
AB  - The genetic disorders are chronic in nature and, therefore, require continuous
      support and health care. Consequently, the genetic diseases cause formidable
      economic and psychosocial burdens on the family with negative reflection on the
      community at large. The genetic diseases are a heterogeneous group that result in
      varieties of chronic health ailment as a result of defects in the genetic
      material. The congenital malformations and some genetic defects may result from
      exposure to radiation, pharmaceutical drugs, the exposure of the mother during
      pregnancy to certain infectious diseases, such as rubella, toxoplasma or viruses.
      It may also result as a side effect of chronic diseases, including diabetes,
      hypertension or varieties of environmental factors, or both. The other group of
      genetic diseases are transmitted from parents to the offspring through a specific
      pattern of inheritance exemplified by recessive genetic disorders. This group
      includes the sickle cell gene, the thalassemias, the hemophilias, inborn errors
      of metabolism and red cell enzymopathies. The main etiological factors of genetic
      diseases and congenital malformations are 1) Genetic defects which are
      transmitted to offspring through carriers of affected parents. 2) Mutations in
      the genetic materials due to spontaneous mutations, exposure of the mother during
      pregnancy to infectious diseases, such as rubella and toxoplasma, receiving
      certain teratogenic drugs during pregnancy, exposure of the mother to ionizing
      radiation during pregnancy such as x-ray and chronic diseases of the mother, such
      as diabetes mellitus. 3) Others such as difficult labor or injury to the baby,
      during or after labor. This paper reviews the natural history of common blood
      genetic disorders and the means of prevention and control, focusing on pre
      marital screening as a means of prevention.

PMID- 15573177
TI  - Towards evidence-based clinical practice guidelines in Saudi Arabia.
AB  - The objective of this review is to provide a brief background on clinical
      practice guidelines CPGs and tools to assess and locally adapt CPGs. Over the
      last 2 decades, CPGs have become an increasingly popular tool for synthesis of
      clinical information, so as to change clinical practice and improve quality of
      health care. Such a quantitative growth in the number of guidelines available in
      different specialties is a source of concern since there is evidence that
      recommendations produced by different groups can be conflicting, invalid,
      unreliable, and even harmful. Various critical appraisal instruments were
      designed and tested to assess whether developers have minimized the biases
      inherent in creating guidelines and addressed the requirements for effective
      implementation. We recommend using the AGREE instrument which was developed by
      the Appraisal of Guideline Research and Evaluation AGREE collaboration. It is the
      most well-developed guideline appraisal instrument available, and it has been
      shown to have good reliability and validity. There is a growing recognition that
      it is not possible for national guidelines to be produced on every clinical
      problem of concern. The cost is huge and few practices have the resources or
      skills to develop their own valid evidence-based guidelines. Several developed
      countries encourage local adaptation of international good quality guidelines to
      avoid duplication of work and cost involved in guidelines development. Therefore
      wherever possible, Saudi guidelines should be based on existing good quality
      guidelines. The methodology for local adaptation of CPGs to meet the local needs
      and resources are explained in this review.

PMID- 15573178
TI  - Human immunodeficiency virus in Saudi Arabia.
AB  - The human immunodeficiency virus HIV type 1 has evolved as one of the most
      important global infectious pathogens. Although the virus had initially emerged
      among certain high risk groups in developed countries, it quickly gained momentum
      in developing countries threatening most population groups. The first case of
      acquired immunodeficiency syndrome from the Kingdom of Saudi Arabia was diagnosed
      in 1984. Twenty years later, by the end of 2003, 1509 patients have been reported
      to have acquired HIV 1. The majority of the early infected patients have acquired
      HIV 1 from blood product transfusion. Subsequently, the most prevalent mode of
      transmission became heterosexual. In this review, the distribution of HIV
      infected persons, prevalence data, and future outlook are presented. Communities
      considered conservative are not immune from a sexually transmissible virus that
      has infected 60,000,000 people globally.

PMID- 15573179
TI  - Saudi women in academic medicine. Are they succeeding?
AB  - OBJECTIVE: The main purpose of this study is to assess the achievements and
      barriers to advancement for Saudi women in a medical academic setup. METHODS: We
      studied the career progression of female medical graduates, who were appointed an
      academic position in King Faisal University, Dammam, Kingdom of Saudi Arabia
      (KSA) between 1982 and 2003 and compared it to the male counterpart. The
      information was collected from the Dean's ship of admission and registration,
      employees and faculty affairs administration office, self completed and telephone
      surveys. RESULTS: The percentage of medical graduates who were appointed on an
      academic post in the University was 4.4% for females and 4% for males. The
      females specialized in various fields and progressed equitably with the males in
      their postgraduate studies. Academic promotion to higher ranks was slower for
      females in comparison to males. This was related to various reasons related to
      family responsibilities, social strains, lack of family friendly policies in the
      institutions, lack of mentoring relationship, and bias against females.
      CONCLUSION: Saudi women in academic medicine have succeeded at the junior level.
      They specialized in various fields and excelled. Their further academic
      progression needs the support of senior academic staff, the chairs and the
      institution administration.

PMID- 15573180
TI  - Polymorphism of p53 gene in Jordanian population and possible associations with
      breast cancer and lung adenocarcinoma.
AB  - OBJECTIVE: To determine the prevalence of 3 polymorphisms in p53 gene in 3
      healthy Jordanian groups and 2 cancer patient groups. METHODS: Genomic DNA was
      extracted from blood samples obtained from 84 cancer patients (breast and lung
      adenocarcinoma) and 136 healthy subjects (representing Jordanian general
      population, Bedouins and Charkas). Samples were collected from Al-Amal Hospital
      for Cancer, Amman and from health centers located in different regions of Jordan
      from March 2002 to October 2002. Polymerase chain reaction (PCR) was used to
      amplify intron 3, exon 4 and intron 6 and PCR products were analyzed using gel
      electrophoresis and BstUI and MspI analysis. Allele frequencies (A1) were
      estimated for the 3 polymorphisms and Chi-square (chi2) test was used to
      determine the significance of differences from the Hardy-Weinberg equilibrium.
      RESULTS: Differences in allele frequencies for all 3 polymorphisms were observed
      among the various groups. Analysis based on haplotype frequencies showed that
      MspI A2 allele linked to BstUI allele was associated with lung adenocarcinoma,
      whereas the loss of the 16-bp duplication allele in combination with MspI A2
      allele was associated with breast cancer. In the cancer patients, the most
      frequent extended haplotype was the absence of the 16-bp duplication in
      combination with the presence of the BstUI A2 and MspI restriction sites.
      CONCLUSION: No significant difference was found with respect to the BstUI
      polymorphism between cancer patients and healthy groups. However, a significant
      difference was found with respect to the MspI polymorphism between lung
      adenocarcinoma patients and healthy Jordanian general population. Charkas have a
      higher cancer risk than Jordanian general population based on the (16bp A1-MspI
      A2) for breast cancer and (MspI A2-BstUI A2) for lung adenocarcinoma.

PMID- 15573181
TI  - Breast self-examination among Saudi female nursing students in Saudi Arabia.
AB  - OBJECTIVE: The purpose of this study was to investigate the knowledge and
      practice of breast self-examination (BSE) among Saudi female nursing college
      students in Riyadh, Kingdom of Saudi Arabia (KSA). METHODS: A cross-sectional
      study was conducted between October and December 2003. Saudi female nursing
      students (149) from the College of Applied Medical Sciences, King Saud
      University, and from the College of Nursing, King Abdulaziz Medical City,
      National Guard, Riyadh, KSA, constituted the study population. The questionnaire
      contained items on the demographic characteristics of the respondents, knowledge
      of breast cancer, attitudes toward BSE and questions regarding the practice of
      BSE. The analysis included descriptive statistics and chi-squared tests to
      examine the association between BSE and demographic, medical history, knowledge
      of BSE and attitudes toward BSE. RESULTS: The results of the study indicated that
      66% of the sample performs BSE. Approximately 62% of those who perform BSE said
      they learned information regarding BSE in their college curricula. The
      significant relation was found between higher levels in nursing college and BSE
      practice. Except for age, no significant relation was found between the socio
      demographic factors and BSE practice. The sample showed strong belief in nipple
      discharge as a causing factor of breast cancer and had significant correlation
      and BSE practice. CONCLUSION: Positive correlations were found between nursing
      students BSE practice and their academic experience in nursing college. Studies
      like these can enhance the knowledge regarding BSE among nurses and other medical
      professionals.

PMID- 15573182
TI  - Age distribution of nasopharyngeal cancer in Saudi Arabia.
AB  - OBJECTIVE: The age standardized rate of head and neck cancer in the Kingdom of
      Saudi Arabia (KSA) is 5.7% with nasopharyngeal cancer (NPC) accounting for >40%
      of all head and neck cancers. This study intends to compare age specific
      incidence of NPC in KSA and other countries. METHODS: Data from the National
      Cancer Registry for KSA during the period 1994 through to 1996 was compared with
      data from the World Health Organization International Agency for Research on
      Cancer (ARC) in Singapore, China, Kuwait and Canada. RESULTS: There were 373
      diagnosed Saudi patients with NPC with high incidence among the young population,
      with 42/373 (22 males/20 females) patients in the first 20 years of life, showing
      a sharp increase both in boys and girls until the ages of 12-14 years. From that
      point the incidence curve for both males and females separates. In females the
      incidence flattens without an identifiable zenith from the age of 12-14 years and
      above, compared with their male counterpart where they have another peak in the
      fifth decade. CONCLUSION: Our study indicates a definite early onset of this
      malignancy in KSA and a similar pattern to that of China and Singapore. Definite
      increased incidence, at a young age among both sexes, suggests a possible
      underlying genetic susceptibility in Saudis.

PMID- 15573183
TI  - Renal cell carcinoma in children. Prognostic factors.
AB  - OBJECTIVE: To determine the outcome in childhood renal cell carcinoma and the
      role of surgical and radiation treatment. METHODS: The records of 21 children
      with renal cell carcinoma were reviewed, 15 patients treated in the University of
      Toronto centers from 1959 through to 1997 and 6 patients treated in King Faisal
      Specialist Hospital, Riyadh, Kingdom of Saudi Arabia from 1975 through to 1998.
      The age was 3-17 (median 13) years. Systematic metastases were present at
      diagnosis in 5 patients. Regional nodal spread was present in 9 patients and 7
      patients had localized disease alone. In the 16 M0 patients, the surgical
      treatment was radical nephrectomy (14 patients) partial nephrectomy (one patient)
      and wedge resection (one patient). Postoperative radiation treatment was utilized
      in 8 (50%) of these patients. RESULTS: The 5 year survival rate for all patients
      was 52%, and for M0 patients was 70%. No patient with systematic metastases at
      diagnosis survived beyond 26 months. Four of 7 node negative patients and 8 of 9
      node positive patients remained in first complete remission, with the duration of
      follow up 1-30 (Median 5) years. Seven of 8 M0 patients who did not receive
      adjuvant radiation therapy continued in first remission (3N0, 2NI, 2N2), compared
      with 5 of 8 patients who received postoperativeradiation treatment (1 N0, 2 NI, 2
      N2). CONCLUSION: The prognosis of localized renal cell carcinoma in childhood may
      be better than in the adult. Gross complete resection is required for long term
      survival. Elective postoperativeradiation treatment is not indicated.

PMID- 15573184
TI  - Flow cytometric evaluation of bone marrow plasma cells using CD19, CD45, CD56,
      CD38, and CD138 and correlation with bone marrow infiltration ratio in multiple
      myeloma patients.
AB  - OBJECTIVE: To examine the co-expression of CD19, CD45, CD38, CD56, and CD138
      molecules in plasma cells of bone marrow (BM) aspirates and their relation with
      BM infiltration, and treatment in patients with multiple myeloma by flow
      cytometry. METHODS: Forty BM aspirate samples were assessed from 40 patients at
      diagnosis and on follow-up at the Medical Oncology Department, Cukurova
      University, Balcali Hospital, Turkey, between 2002 and 2004. The mean age was
      56.83 +/- 9.1 and male:female ratio was 2.6. All patients received at least 4
      courses of VAD(vincristine, adriamycin, dexamethasone) regimens and 20 of them
      were also treated with high dose melphalan and peripheral autologous stem cell
      transplantation. The median follow-up period was 19.1 +/- 22.7 months. RESULTS:
      Using light microscopy the BM smears stained with hematoxylin and eosin from
      patients on follow up were classified into one of 3 categories, complete
      remission (CR) (<5%), partial remission (PR) (>5% and <30%), and extensive
      infiltration (EI) (>30%). According to infiltration ratio 23 were evaluated CR, 2
      were PR and 15 were EI. The mean value of CD19 was 6.01 +/- 9.5%, CD56 = 9.9 +/-
      6.8%, CD138 = 8.6 +/- 5.6%, CD45 = 84.2 +/- 22.3% and CD38 = 59.5 +/- 25.4%. The
      flow cytometric analyses revealed that only the mean value of CD38 and CD45
      expression were significantly high. We correlated infiltration ratio with each
      parametric and found statistically significant relations. We also correlated
      independent variables with each other and found a relation between CD38 and CD19
      (p=0.005). We also defined the groups whether treated with peripheral autologous
      transplantation or not and compared the independent variables between them, in
      which CD138 was statistically significant (p=0.02). CONCLUSION: We suggest BM
      plasma cells expressed mainly by CD38 and CD45 may have a role in generation of
      BM plasma cells and that CD138 expression may be considered in follow-up for
      minimal residual disease after autologous transplantation in myeloma patients.

PMID- 15573185
TI  - Plasma fibrinogen and its correlates in adult Saudi population.
AB  - OBJECTIVE: To determine plasma fibrinogen and its correlates in the adult Saudi
      population and to investigate hyperfibrinogenemia as a possible risk factor for
      cardiovascular diseases (CVD). METHODS: A cross-sectional survey was designed and
      carried out through multi-stage stratified cluster random sampling of every third
      house in 6 heterogeneously populated districts of Riyadh, Kingdom of Saudi
      Arabia, during the period 1999 to 2002. Demographic and clinical data of 2263
      adult Saudi subjects, consisting of 1934 (85.5%) men and 329 (14.5%) women, was
      collected through a standard questionnaire. Body mass index (BMI), blood pressure
      (BP) and history of smoking were recorded. Plasma fibrinogen, total serum
      cholesterol, triglycerides, high density lipoproteins (HDL) and blood sugar were
      determined in fasting blood samples. RESULTS: The majority (84.6%) of the
      subjects were between 20-50 years of age. The mean plasma fibrinogen was 336 +/-
      115 mg/dl, and was increasing with age both in men and women. The mean +/- SD
      fibrinogen in women (357 +/- 118 mg/dl) was significantly higher (p value of
      0.03) than men (332 +/- 114 mg/dl). Hyperfibrinogenemia (>400 mg/dl) was
      indicated in 554 (24.6%) of the total subjects. Among hyperfibrinogenemic Saudi
      adults, the prevalence of hypercholesterolemia was 14.3%, hypertriglyceridemia
      24%, obesity 26.3%, systolic/diastolic hypertension 11.5% and 11% and
      hyperglycemia 26% (in women only). A reciprocal relation was observed between HDL
      and plasm fibrinogen. Significant positive correlation was seen between
      fibrinogen and BMI, systolic and diastolic BP and total cholesterol. There was no
      significant difference in the distribution of plasma fibrinogen between smokers
      and non-smokers (p value of 0.864). The difference in the magnitude of metabolic
      as well as modifiable CVD risk factors between smokers and non-smokers was not
      significant, except serum triglyceride which was significantly higher in smokers
      than non-smokers (p value of 0.020). CONCLUSION: A significant positive
      correlation was observed between hyperfibrinogenemia and obesity,
      systolic/diastolic hypertension and hypercholesterolemia. Our results thus
      support the earlier reports that hyperfibrinogenemia is a potential CVD risk
      factor. Unlike other reports, we could not find any correlation between smoking
      and plasma fibrinogen in our studied subjects. The value of hyperfibrinogenemia
      as a definite risk factor for CVD has to be quantified in future case-control
      studies comparing its significance between CVD subjects and normal controls.

PMID- 15573186
TI  - Diabetes mellitus in Saudi Arabia.
AB  - OBJECTIVE: Diabetes mellitus (DM) is a major public health problem worldwide, and
      it is a known risk factor for coronary artery disease (CAD). New recommendations
      for the diagnosis of diabetes have changed the epidemiology of DM. Therefore, we
      designed this study with the objective to determine the prevalence of DM among
      Saudis of both sexes, between the ages of 30-70-years in rural as well as urban
      communities. This work is part of a major national project: Coronary Artery
      Disease in Saudis study (CADISS) that is designed to look at CAD and its risk
      factors in Saudi population. METHODS: This study is a community-based national
      epidemiological health survey, conducted by examining Saudi subjects in the age
      group of 30-70-years of selected households over a 5-year period between 1995 and
      2000. Data were obtained from history, fasting plasma glucose levels, and body
      mass index. The data were analyzed to classify individuals as diabetic, impaired
      fasting glucose and normal, using 1997 American Diabetes Association (ADA)
      criteria, which was adopted by the World Health Organization (WHO) in 1998, to
      provide prevalence of DM in the Kingdom of Saudi Arabia (KSA). RESULTS: A total
      of 17232 Saudi subjects were selected in the study, and 16917 participated (98.2%
      response rate). Four thousand and four subjects (23.7%), out of 16917 were
      diagnosed to have DM. Thus, the overall prevalence of DM obtained from this study
      is 23.7% in KSA. The prevalence in males and females were 26.2% and 21.5%
      (p<0.00001). The calculated age-adjusted prevalence for Saudi population for the
      year 2000 is 21.9%. Diabetes mellitus was more prevalent among Saudis living in
      urban areas of 25.5% compared to rural Saudis of 19.5% (p<0.00001). Despite the
      readily available access to healthcare facilities in KSA, a large number of
      diabetics 1116 (27.9%) were unaware of having DM. CONCLUSION: The overall
      prevalence of DM in adults in KSA is 23.7%. A national prevention program at
      community level targeting high risk groups should be implemented sooner to
      prevent DM. We further recommend a longitudinal study to demonstrate the
      importance of modifying risk factors for the development of DM and reducing its
      prevalence in KSA.

PMID- 15573187
TI  - Plasma concentrations of non-esterified fatty acids in chronic renal failure in
      the United Arab Emirates.
AB  - OBJECTIVE: In end-stage renal failure, dyslipoproteinemia is linked to risk of
      cardiovascular disease. Increased concentrations of triacylglycerol-rich, very
      low density lipoproteins (VLDL) and decreased concentrations of high density
      lipoproteins (HDL) are usual, whilst total cholesterol and low density
      lipoprotein (LDL) concentrations are not increased. Non-esterified fatty acids
      (NEFA) are not transported by lipoproteins, but increased concentrations may also
      be associated with cardiovascular disease risk. In this study, plasma
      concentrations of NEFA and other lipids were compared in healthy subjects and
      patients with end-stage chronic renal failure who were either undialyzed or
      undergoing peritoneal dialysis or hemodialysis. METHODS: Fasted blood samples for
      measurement of albumin, total, free and HDL-cholesterol, triacylglycerols and
      NEFA were taken from 56 apparently healthy subjects and from 48, 28 and 46
      patients from the United Arab Emirates during 2002 who were either untreated or
      on peritoneal or hemodialysis. Hemodialysis subjects were studied immediately
      before and after a single treatment session. RESULTS: For all groups of patients,
      total, and LDL-cholesterol were unchanged, triacylglycerols and free cholesterol
      were raised and HDL-cholesterol concentrations and the percentage of esterified
      cholesterol were significantly decreased compared to controls. Plasma NEFA
      concentrations for untreated patients were similar to controls, but were
      decreased in peritoneal dialysis patients and markedly increased both before and,
      even more so, after dialysis in hemodialysis patients. CONCLUSION: Patients with
      end-stage renal failure share common features of dyslipoproteinemia irrespective
      of whether they are untreated or on peritoneal dialysis or hemodialysis. However,
      only hemodialysis patients show significantly increased concentrations of NEFA.

PMID- 15573188
TI  - Leptin concentration during different trimesters of pregnancy and its relation to
      other pregnancy hormones.
AB  - OBJECTIVE: To determine the levels of leptin and other pregnancy hormones
      (progesterone, estradiol, folliculi stimulating hormone, luteinizing hormone and
      beta human chorionic gonadotropin) in pregnant females during different stages of
      pregnancy and to correlate these levels to maternal weight, body mass index
      (BMI), babies weight and babies BMI. METHODS: Leptin level and other pregnancy
      hormones were measured in 36 pregnant females and 30 non-pregnant females
      followed at King Khaled University Hospital, Riyadh, Kingdom of Saudi Arabia in
      the year 2001 in a prospective study. Blood samples were collected at the first,
      2nd and 3rd trimester and after delivery. Correlation analysis between leptin
      level and pregnancy hormones, in addition to maternal weight, BMI, babies weight
      and BMI. RESULTS: The mean leptin levels during pregnancy and postnatally were
      significantly higher in pregnant females compared to the non-pregnant controls.
      Serum concentration of leptin increased significantly (p=0.01) in the pregnant
      females from 21.24 +/- 9 ng/ml during the first trimester to 26.3 +/- 8.69 ng/ml
      during the 2nd trimester, but insignificantly decreased to 23.29 +/- 8.62 ng/ml
      during the 3rd trimester (p=0.073). After delivery leptin concentration
      significantly decreased to 17.36 +/- 7.95 ng/ml (p=0.0025). The changes in levels
      of leptin during pregnancy were independent to other pregnancy hormones which
      showed a different pattern of variation. CONCLUSION: The changes in levels of
      leptin during pregnancy were independent to other pregnancy hormones which showed
      a different pattern of variation.

PMID- 15573189
TI  - Bone mineral density among postmenopausal Saudi women.
AB  - OBJECTIVE: Osteoporosis is reported to be common among postmenopausal Saudi
      women. The reported incidence varies between 50-60%. Different machines were used
      to reach these conclusions. At present it is believed that dual energy x-ray
      absorptiometry (DEXA) is the most accurate method to diagnose osteoporosis. This
      study was conducted to measure bone mineral density (BMD) measurement of lumbar
      spine and the upper femur of Saudi postmenopausal women attending orthopedic
      clinic with unrelated complaints. METHODS: This study comprises of 256 patients
      attending orthopedic clinics at the King Fahd Hospital of the University, Al
      Khobar, Kingdom of Saudi Arabia between January 2002 and June 2003. The data
      gathered was age, duration of menopause, height and weight for body mass index
      (BMI) calculation. Women with secondary osteoporosis were excluded from the
      study. Patients' orthopedic complaints were also recorded in the database. Bone
      mineral density measurements were carried out using Hologic total body DEXA
      machine. The data were analyzed using SPSS package. RESULTS: The data of 256
      patients was available for analysis. The average age of patients screened was
      57.62 years (49-76) SD +/- 6.71. The BMI was 21.3-42.9 Kg/m2 (SD +/- 5.34). The
      BMD of the lumbar spine was 0.785 gm/cm2 (0.527-1.023) SD +/-0.142 and that of
      the hip region was 0.764 gm/cm2 (0. 500-1.069) SD +/- 0.149. As per the WHO
      classification 59 women (23%) were classified as normal with T score of -0.82, 78
      (30.5%) as osteopenic with T score -2.5 and 119 (46.7%) as osteoporosis with T
      score -3.58. When the BMD of the hip was analyzed 62 (24.2%) were normal T score 
      1.0, 81 (31.6%) as osteopenic, T score -2.5 and 113 (44.1%) as osteoporotic, with
      a T score of -3.1. On the basis of analysis of the lumbar spine 190 (74.2%) had
      increased risk of fracture as compared to the analysis of hip 59% were at
      increased risk of fracture. CONCLUSION: Our results indicate that postmenopausal
      Saudi women suffer from osteoporosis and osteopenia higher than those from other
      parts of the country. Necessary steps are needed so as to avoid osteoporosis and
      its complications which could end up in epidemic proportions.

PMID- 15573190
TI  - Cultural and ethnic barriers in conducting research. Factors influencing menarche
      in the United Arab Emirates.
AB  - OBJECTIVE: The objective of this cross sectional survey was to study the
      feasibility of conducting research on issues related to physical and sexual
      maturation in a predominantly Islamic society and to identify the factors
      influencing menarche in this multi ethnic community. METHODS: This study was
      conducted in Al-Ain, United Arab Emirates (UAE) between January 1999 through to
      February 1999. Fifteen female secondary schools located in different geographical
      regions in Al-Ain were chosen in consultation with the District Education
      Department. All girls aged 12-16-years were selected. Information regarding
      whether they had attained menarche including month and the year, age at menarche
      and the factors influencing it such as height and weight, diet, physical activity
      were gathered. Univariate and multiple linear regressions were used in analysis.
      RESULTS: Of the 1500 questionnaires distributed, 1416 questionnaires were
      returned but only 890 had the required information and were used in the analysis.
      Ninety-three (10.4%) had not attained menarche and as expected these girls were
      younger (p<0.0001) than those who had attained menarche. Mean age at menarche was
      12.68 (SD 1.27) years. In the univariate analysis UAE nationality, vegetarians
      (p=0.001), higher income group (p=0.008), low body weight (p=0.009) and a
      diagnosis of anemia (p<0.05) in the year before menarche were all positively
      associated with the age at menarche. Only anemia achieved borderline significance
      (p=0.056) in multivariate analysis and no other variables were significant.
      CONCLUSION: This study highlights the difficulties of conducting research on
      issues considered to be sensitive by the community and provide data on factors
      influencing menarche in a multi ethnic community.

PMID- 15573191
TI  - The Jordanian cesarean section rate.
AB  - OBJECTIVE: This study was conducted to determine the Jordanian cesarean rate and
      to examine the related indications for cesarean section (CS) in comparison with
      international rates. METHODS: Between 1990 to 2001, there were 243271 deliveries
      at 7 major military hospitals, (King Hussein Medical Center; Queen Alia Hospital,
      Amman; Prince Hashem Ben Al-Hussein Hospital, Al-Zarqa; Prince Ali Ben Al-Hussein
      Hospital, Al-Karaq; Prince Zaid Ben Al-Hussein, Al-Tafileh; Prince Rashid Ben Al
      Hassan, Irbid; Princess Haya Al-Hussein, Aqaba) that reflect the main cities in
      Jordan, of which 22621 CS were performed. Two periods for the study were taken,
      the first from January 1990 to December 1992 and the second from January 1999 to
      December 2001 to examine the changes in the rate and indications for CS. Cesarean
      deliveries were classified according to 5 indications: breech presentation,
      dystocia, repeat cesareans, fetal distress and "others". Comparison by indication
      between the 2 periods and with the United States of America (USA) studies was
      discussed. Significance of differences was assessed using Chi-Square test.
      RESULTS: Out of 48280 deliveries performed during the first period, 3854 CS were
      performed with an incidence of 8%, while 8353 CS were performed during the second
      period out of 76611 deliveries with an incidence of 10.9%. This difference in
      rate showed 2.9 per hundred deliveries increase in the cesarean rate between the
      2 periods. Comparison between the 2 periods showed no significant change in CS
      rate for breech category (p=0.158). A highly significant increase was found for
      fetal distress category (p=0.000), while dystocia and repeat CS showed a high
      significant decrease in CS rate (p=0.000) in the second study period. Analysis of
      the Jordanian CS rate and related indications for the operation compared with USA
      reports showed a high significant increase in Jordanian cesarean rate for breech,
      fetal distress and "other" categories (p=0.000), while a high significant
      decrease for dystocia and repeat cesarean was found (p=0.000). CONCLUSION: The
      lower cesarean rate in Jordan is attributed to lower frequencies of CS for
      dystocia, due to more accuracy in estimation of the fetal body weight, and with
      proper use of oxytocin dosage, which can correct malrotation of vertex leading to
      subsequent reduction in CS rate for dystocia. Policies, such as: active
      management of labor, trial of scar, maintenance of the skills required to
      supervise vaginal delivery when there is a breech presentation and better
      definition of the deliveries in which fetal monitoring will be useful in the
      diagnosis of fetal distress; all will achieve acceptable cesarean rate.

PMID- 15573192
TI  - Use of dexamethasone to reduce postoperative vomiting and pain after pediatric
      tonsillectomy procedures.
AB  - OBJECTIVE: The purpose of this study is to determine whether a single dose of
      dexamethasone 0.5mg/kg administered before surgery could decrease post operative
      vomiting and pain and improves oral intake in the first 24-hours after pediatric
      tonsillectomy procedures. METHODS: It is a randomized, double blind, placebo
      controlled study. Sixty children age 2-12-years ASA 1 and 11 were scheduled for
      tonsillectomy, dexamethasone (n=29) and control group (n=31) were enrolled in the
      study. Dexamethasone group received 0.5mg/kg intravenous dexamethasone and
      control group received saline at the time of induction. The anesthetic regimen
      and surgical procedures were standardized for all patients. All patients were
      observed in post anesthesia care unit (PACU) and ward for post operative
      vomiting, pain, need for rescue antiemetic or analgesia and time for first oral
      intake for 24-hours. RESULTS: Data from 60 patients were analyzed. The overall
      incidence of early as well as late vomiting was significantly less in
      dexamethasone as compared to control group (37% versus 74% P=0.016), overall
      incidence of retching was 29% in control and 3.4% in dexamethasone (p=0.008).
      Vomiting once or more than once was significantly high in control as compared to
      dexamethasone group. The need for rescue antiemetic, the time to first oral
      intake and analgesic requirements did not show any significant difference in both
      groups. CONCLUSION: Dexamethasone is considered safe and there was no adverse
      effects associated with a single dose of dexamethasone. Although the need for
      rescue antiemetic, time to oral intake and analgesia requirements in both groups
      were not significant, however, we found that dexamethasone does have antiemetic
      properties as overall incidence of retching and vomiting was significantly less
      in dexamethasone group as compared to control group in children who underwent
      tonsillectomy.

PMID- 15573193
TI  - Brucellosis in the West Bank, Palestine.
AB  - OBJECTIVE: To identify the risk factors for brucellosis in Palestine, to estimate
      their association with the disease and to recommend appropriate prevention
      measures. METHODS: An unmatched case-control study was conducted in the West Bank
      of Palestine. A total of 450 subjects (150 cases and 300 controls) chosen from
      all districts were investigated. Data were collected during the year 2000.
      Subjects were interviewed using a standard questionnaire acquiring demographic
      and risk factor information. Laboratory results were also recorded on the
      questionnaire. Data were analyzed calculating the odds ratio and the confidence
      intervals for the studied variables. A logistic regression model was used to
      explore the association between disease status and the studied variables.
      RESULTS: Several variables were significantly associated with brucellosis
      involving both direct and indirect transmission such as consumption of
      unpasteurized milk and dairy products, herding, lambing and others. CONCLUSION:
      Most of the risk factors for being infected with brucellosis are modifiable.
      Efforts should be directed to the prevention of this major public health problem
      in Palestine utilizing the information obtained in this study.

PMID- 15573194
TI  - Evaluation of a PCR-amplified IS6110 insertion element in the rapid diagnosis of
      pulmonary tuberculosis in comparison to microscopic methods in Sudan.
AB  - OBJECTIVE: The aim of this study was to evaluate the sensitivity and specificity
      of a polymerase chain reaction (PCR)-based method (IS6110 insertion site) in the
      diagnosis of pulmonary tuberculosis in sputum samples in comparison to smears by
      using culture on Loewenstein-Jensen medium as a standard. METHODS: The study was
      conducted during the period 1999 through to 2000, at Khartoum Teaching Hospital,
      Sudan, on 200 sputum samples. The samples were collected from patients suspected
      of having pulmonary tuberculosis, were examined using a PCR amplified IS6110
      insertion element in comparison to Ziehl-Neelsen stained smears in terms of
      sensitivity and specificity. Culture on Loewenstein-Jensen medium was used as the
      standard to control the 2 tests. RESULTS: Microscope sensitivity was found to be
      65.4% and the specificity was 90.5%, whereas sensitivity of the IS6110 was 88.5%
      and specificity was 98.6%. CONCLUSION: The study concluded that though IS6110
      sensitivity was 13.1% higher than smear method, it provided a significant
      improvement in specificity for the diagnosis of pulmonary tuberculosis.
      Improvement is still needed to increase the sensitivity of the IS6110 methods by
      decreasing the number of the false negative samples before its use can be at
      routine levels.

PMID- 15573195
TI  - Light and scanning electron microscopic examination of late changes in hair with
      hereditary trichodysplasia (Marie Unna hypotrichosis).
AB  - OBJECTIVE: Our aim was to investigate the microscopic surface structural
      alteration in hair with hereditary trichodysplasia. This article presents the
      results of light and scanning electron microscopy (SEM) examination of cases
      having hereditary trichodysplasia. METHODS: The biopsy specimens were obtained
      from 2 girls of ages 3 and 5-years, Department of Pediatrics, Faculty of
      Medicine, Hacettepe University in 2001. A large number of hair specimens were
      obtained from these 2 cases having hereditary trichodysplasia. Routine light
      microscopic and SEM procedure was performed on the tissue specimen, and then they
      were examined by light microscopy and SEM. RESULTS: Hair specimens taken from
      both patients had great similarities. Our results reveal that the atypical
      looking hair were flattened, twisted and partly scattered at the end. Moreover,
      these hairs had sheath structures with abnormal proliferation and these
      structures were damaged, the cuticles had fractures and were degenerative.
      CONCLUSION: There is only a small number of SEM studies in literature reporting
      the ultrastructural changes of hereditary trichodysplasia. Scanning electron
      microscopy is a 3 dimensional examination technique revealing easily comparable
      images and it is indispensable for diagnosis in various tissues which permit
      considerable magnification. As it is used in the hereditary trichodysplasia
      syndrome its routine usage in many dermatologic and hair diseases will result in
      valuable contributions to scientific literature.

PMID- 15573196
TI  - Dermatological publications in the Gulf Cooperation Council countries. An
      analysis of 1966-2004 Medline papers.
AB  - OBJECTIVE: To investigate the publications in dermatology cited in the Medline
      from 6 countries of the Gulf Cooperation Council (GCC) from 1966 to 2004.
      METHODS: Medline was searched with the aid of Internet provider Pubmed using the
      same strategy at a given time for all countries. RESULTS: At the time of search,
      the Medline listed biomedical research papers from the GCC countries totaled
      12837. Of these, 140 were in Dermatology. The Kingdom of Saudi Arabia followed by
      Kuwait was by far the most prolific contributor, whereas almost none were noted
      from Bahrain. The publications were highest during the year 2002 (19) followed by
      2003 (13), most of them being in the English language in the International
      Journal of Dermatology (60 citations) and Pediatric Dermatology (13 citations).
      CONCLUSION: Though the GCC countries have seen a relatively small period in the
      history of development of medical research, data show that they are trying to
      keep pace with the rest of the developed world. What remains to be exploited is
      their good economy that should be directed to provide better infrastructure and
      improve the quality of training programs. Professional societies within the
      region must play an active role in ensuring optimum and judicious use of funds.

PMID- 15573197
TI  - Short- and long-term effects of acetylsalicylic acid treatment on the
      proliferation and lipid peroxidation of skin cultured melanocytes of active
      vitiligo.
AB  - OBJECTIVE: Recent in vitro and in vivo studies have shown that the nonsteroidal
      anti-inflammatory agent, acetylsalicylic acid (ASA) or aspirin has antioxidant
      properties on various cell lines and tissues. Hence, the aim of the present study
      is to investigate the effects of ASA at 2 different concentrations (75 and 300
      microg/ml) on the proliferative capacities and lipid peroxidation of in vitro
      skin cultured melanocytes obtained from patients with active vitiligo. METHODS:
      The present work was carried out from February 2001 through to November 2001, at
      the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of
      Saudi Arabia. Employing methods described in this section, cryopreserved primary
      cultured melanocytes that were originally cultured from skin biopsies of normal
      healthy individuals and patients with active vitiligo (n=7), were subcultured to
      confluence. The malondialdehyde (MDA) concentrations in the cell culture medium
      were determined at 6 hours and 21 days following cultured melanocytes treatment
      with ASA (75 and 300 microg/ml). Also, the number of viable melanocytes was
      determined 21 days following the treatment of melanocytes with ASA (75 and 300
      microg/ml). RESULTS: Following ASA treatment at 75 microg/ml, the cultured
      melanocytes from the normal and active vitiligo donors showed significant
      increase in the proliferative capacities as judged by the increase in the number
      of viable melanocytes after 21 days of cell culture (28.2% and 26.9%, p<0.001).
      Concomitantly, the same ASA concentration resulted in significant decrease in the
      concentrations of MDA in the cell culture medium of the normal and active
      vitiligo melanocytes 6 hour and 21-day period following the ASA treatment [6
      hour: 16.2% (p<0.05) and 18.4% (p<0.001); 21 day: 32% and 38.6% (p<0.001)].
      However, the long-term (21 days) treatment of cultured melanocytes from the
      normal and active vitiligo donors with ASA at 300 microg/ml resulted in a
      significant reduction in the number of viable melanocytes (33.6% and 63.5%,
      p<0.001). Whereas, MDA concentrations 6 hour and 21-day period following the ASA
      treatment had significantly increased [6 hour: 28.6% (p<0.05) and 41.3% (p<0.001)
      21 day: 92.8% and 127.8% (p<0.001)]. CONCLUSION: Low-dose ASA (75 microg/ml) may
      confer protection of skin melanocytes from the normal and active vitiligo donors
      against lipid peroxidation and up-regulate their proliferative capacities. On the
      other hand, high-dose ASA (300 microg/ml) may have deleterious effects on the
      melanocytes, increasing lipid peroxidation and hence may potentiate melanocyte
      apoptosis.

PMID- 15573198
TI  - Seroprevalence of Bartonella henselae and Bartonella quintana infections in
      children from Central and Northern Jordan.
AB  - OBJECTIVE: To investigate the prevalence of antibodies to Bartonella henselae
      (B.henselae) and Bartonella quintana (B.quintana) among children from central and
      northern Jordan. METHODS: Sera from 482 children were randomly collected from
      referenced governmental hospitals in the central and northern parts of Jordan
      during the period between January 2001 to March 2003. An indirect
      immunofluorescent assay was used to determine serum antibody titers to B.henselae
      and B.quintana. Sera that were reactive at a dilution >/-1:64 were considered
      positive. In addition, blood from 20 cats belonged to children with high
      B.henselae titers were tested using polymerase chain reaction. RESULTS: Out of
      the 482 serum samples examined, 53 (11%) and 20 (4.1%) had positive antibody
      titers for B. henselae and B.quintana. Bartonella henselae was isolated from 4
      cats that belonged to 3 children with high antibody titers to B.henselae-IgG. The
      seroprevalence of IgG antibodies to B.henselae was significantly higher (P<0.05)
      in children aged 7-10-years than in younger or older ones. Having a cat in the
      household and having a history of cat scratches or bites were strongly associated
      (P<0.01) with seropositivity to B.henselae-specific IgG. Cats ownership and
      history of cat scratches or bites had no impact on the prevalence of B.quintana.
      Seropositivity to B.henselae-specific IgG was significantly higher (P<0.01) in
      children from northern Jordan than in children from central Jordan. CONCLUSION:
      This study substantiates the presence of B.henselae in Jordan, documents the
      seroreactivity to 2 Bartonella antigens, and suggests that cat ownership and
      history of cat scratches or bites are important epidemiological risk factors for
      B.henselae infection in Jordan.

PMID- 15573199
TI  - Unstable pelvic ring injuries. Outcome and timing of surgical treatment by
      internal fixation.
AB  - OBJECTIVE: To evaluate the radiological and functional results of surgical
      treatment of unstable pelvic injuries and to study the factors affecting the
      final outcome. METHODS: Thirty-eight patients with unstable type C pelvic
      injuries from King Khalid University Hospital, Riyadh and North West Armed Forces
      Hospital, Tabuk, Kingdom of Saudi Arabia during the period January 1996 through
      to January 2001 were reviewed. There were 31 males and 7 females. The mean age
      was 37-years. Thirty-two patients had 76 associated skeletal fractures. A
      percutaneous iliosacral screw was carried out for all patients in the study.
      Anterior stabilization was needed for 23 patients. RESULTS: There were 2
      complications of fixation, an iatrogenic S1 root injury and dismantled symphyseal
      plate. The average hospital stay was 29 days and the average time to start
      mobilization was 15 days. The radiological result was satisfactory in 32 patients
      (84%) while functional result was satisfactory in 27 patients (71%). CONCLUSION:
      Unstable pelvic ring injuries should be managed surgically and must be carried
      out as soon as the general condition of the patient allows, even up to 4-weeks.

PMID- 15573200
TI  - The syndrome of septo-optic dysplasia in Saudi children.
AB  - OBJECTIVE: To describe the clinical, ophthalmological, endocrinological and
      radiological features of 10 Saudi children with the syndrome of septo-optic
      dysplasia and hypothalamic hypopituitarism. METHODS: All patients underwent
      complete ophthalmological and endocrinological evaluation at the Pediatric
      Endocrine Clinics, King Faisal Specialist Hospital and Research Center and King
      Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia, from October 1999
      through to May 2004. The hormonal evaluation included growth hormone,
      adrenocorticotrophic hormone, thyroid stimulating hormone, gonadotropin and anti
      diuretic hormone testing, and the neuroradiological assessment included brain
      magnetic resonance imaging or computed tomogram scanning, or both. RESULTS: The
      current age of patients ranged from 18- months to 5-years. The mean age of
      initial presentation for endocrine evaluation was 14-months. Hormonal studies
      indicated that all children had multiple pituitary hormone deficiencies (2 or
      more of the pituitary hormones were deficient). Ten children had growth hormone
      deficiency, 8 had thyroid stimulating hormone deficiency, 8 had
      adrenocorticotrophic hormone deficiency, 2 children were suspected to have
      gonadotropin deficiency and central diabetes insipidus was present in one
      patient. Pendular nystagmus and impaired vision were common initial signs. All
      children had bilateral optic nerve hypoplasia. Neuroradiologic findings were
      variable. Eight children had absent septum pellucidum, 3 had pituitary gland
      hypoplasia, 2 had pituitary stalk dysplasia (pituitary stalk was either
      attenuated or not visualized), 2 had absent corpus callosum and one had absent
      posterior pituitary high intensity signal. All patients were replaced with
      appropriate hormonal replacement therapy. Two male children had micropenis which
      responded to testosterone therapy. CONCLUSION: The syndrome of septo-optic
      dysplasia is commonly associated with hypothalamic hypopituitarism including
      anterior and posterior pituitary hormonal deficiencies. Early diagnosis of this
      syndrome is critical as the hormonal deficiencies can be life threatening.

PMID- 15573201
TI  - Clinical growth charts for pre-school children.
AB  - OBJECTIVE: Growth standards are indicators for normal growth of the children and
      growth charts are important tools for their growth monitoring. Children from
      different populations are different in their growth pattern, it is important to
      create national standards for the growth of children in each population to
      develop local growth charts, and since these were not available in the Kingdom of
      Saudi Arabia (KSA), the aim of this study was to construct national growth
      standards and to develop growth charts for 0-5-years Saudi children. METHODS: A
      cross-sectional study following World Health Organization (WHO) criteria in
      determining sample size was adopted, where by 24000 children from 5 regions in
      the KSA were selected during the period 1992 to 1995 to be the desired sample.
      One hundred and two Primary Health Care centers (PHCCs) were selected randomly
      from the 5 regions, from where the sample was drawn, and a special questionnaire
      was designed. Weight, height and head circumference were measured by standard
      procedures. RESULTS: The total number of children examined was 23821 (11913 boys
      and 11908 girls). Saudi (0-5-years) boys weight and height for age measurements
      were significantly different from girls. The same difference was found between
      urban and rural boys and girls and between boys and girls from the different
      regions of the country (p<0.05). CONCLUSION: These national standards derived
      from this study were used to develop national growth charts that are currently
      utilized to monitor growth in all Saudi health institutes.

PMID- 15573202
TI  - The impact of non-compliance with the therapeutic regimen on the development of
      stroke among hypertensive men and women in Gaza, Palestine.
AB  - OBJECTIVE: Hypertension and stroke are 2 major public health problems worldwide.
      Several biological and non-biological risk factors for stroke have been
      identified in the past. Little is known regarding risk factors for stroke among
      the Arabic population in Gaza. To identify potential risk factors we investigated
      compliance with the therapeutic regimen and life style factors which may increase
      the risk for stroke. METHODS: To research this study question, a pair matched
      case control study was conducted in Gaza Strip (Shefa Hospital, Nasser Hospital,
      Khan Younis Hospital, and related primary health care clinics) in 2001 (from
      January through to December) among 112 patients, who had been hospitalized for
      acute stroke and history of hypertension, and 224 controls with history of
      hypertension from primary health care clinics. RESULTS: Conditional logistic
      regression models show significant associations between stroke and medication not
      taking as prescribed (odds ratio (OR)=6.07; 95% confidence interval (CI)=1.53,
      24.07), using excessive salt at meals (OR=4.51; 95% CI=2.05, 9.90), eating diet
      high in fat (OR=4.67; 95% CI=2.09, 10.40), and high levels of stress (OR=2.77;
      95% CI=1.43, 5.38). No significant association between smoking and the
      development of stroke (OR=2.12; 95 CI 0.82, 5.51) was found. Regular physical
      exercise was a protective factor (OR=0.26; 95% CI=0.12, 0.57). CONCLUSION: Our
      results on risk factors for stroke confirm several other studies. In future
      programs on health promotion among hypertensive men and women in Gaza these
      modifiable risk factors could be addressed by health education strategies.

PMID- 15573203
TI  - Ultrastructural changes of pneumocytes of rat exposed to Arabian incense
      (Bakhour).
AB  - OBJECTIVE: Impacts of air pollution on the human health have been recognized over
      the last decades. Smokes, in particular, have deleterious effects on the
      respiratory system. According to a local tradition, incense "Bakhour" is burnt
      and the resultant heavy smokes are inhaled. The objective of the present study is
      to investigate the ultrastructural pulmonary changes which can be induced by
      Arabian incense, Bakhour, exposure. METHODS: The study was conducted from
      September through to December 2003, at the Animal House, College of Science, King
      Saud University, Riyadh, Kingdom of Saudi Arabia. Two groups of Wister albino
      rats, Rattus norvegicus, were used. One group (n=16) was exposed to 420 grams of
      Bakhour for 14-weeks at the rate of 4 grams/day in the exposure chamber.
      Additional group of rats, of equal number, was used as non-exposed control. At
      the end of the exposure period, lung tissues were removed from all experimental
      animals and processed for electron microscopy. RESULTS: Alveolar pneumocytes of
      exposed animals revealed significant ultrastructural changes which involved the
      cell organelles and surfactant material of type II cells. Hyperplasia of alveolar
      cells was a feature in the affected lung tissue. Neutrophils were recognized
      infiltrating pulmonary alveoli and accompanied with degenerative and necrotic
      changes of the alveolar cells. Deposition of collagen fibrils in the alveolar
      walls was also observed. CONCLUSION: Basing upon the results of electron
      microscopy, it was concluded that exposure to Bakhour can induce ultrastructural
      pulmonary changes which may imply compromised respiratory efficiency.

PMID- 15573204
TI  - Subcutaneous dirofilariasis caused by Dirofilaria repens.
AB  - Human dirofilariasis caused by Dirofilaria repens D. repens is a common zoonosis
      in the Mediterranean countries and parts of South Asia. During the last decade,
      it has been reported from countries previously considered non-endemic. This is
      likely due to the increased awareness regarding Dirofilaria infection. In some
      such cases however, dirofilariasis correlated with the travel of the patient to
      the endemic areas. We present the case of a Saudi male who had D. repens
      infection in the subcutaneous tissues of the forearm. The patient had traveled to
      Iraq, Syria, United Arab Emirates and Kuwait in the last 2 years. However, the
      known Dirofilaria endemic countries were not visited. Any prior occurrence of the
      human dirofilariasis in the Kingdom of Saudi Arabia is not documented. Lack of
      epidemiological studies or incidence reports in the Arabian region precludes any
      factual evaluation of Dirofilaria prevalence, which requires increased awareness
      amongst health workers regarding its potential occurrence in the native
      population.

PMID- 15573205
TI  - Primary ovarian hydatid disease in the Kingdom of Saudi Arabia.
AB  - Human hydatid disease is caused by Echinococcus granulosus. Its distribution is
      world wide and it affects mainly the liver, but other organs could be involved.
      Primary involvement of pelvic organs is very rare. This is a case report of
      primary ovarian hydatid disease in a postmenopausal woman, diagnosed
      postoperatively. Surgical excision was adequate. Ultrasonography, particularly
      high frequency trans-vaginal, computed tomography scan and, more recently,
      magnetic resonance imaging are more frequently used in the diagnosis of
      Echinococcus cyst. They appear more reliable than many of the old tests of
      varying sensitivities. Whereas, there are anecdotal reports of obstetric and
      gynecological manifestations of echinococcosis from some Middle Eastern and North
      African countries, this is the first of such report from the Kingdom of Saudi
      Arabia. It is unclear why there is a lack of information about this condition
      among Saudi women, even though socio-cultural attitude to female involvement in
      sheep farming and animal husbandry is similar to that in other Arabic and Islamic
      countries. We endorse the recommendation that every gynecologist, radiologist and
      histopathologist should maintain a high index of suspicion for hydatid cyst,
      whenever a septate cystic pelvic mass is found.

PMID- 15573206
TI  - Brown tumor of the femur associated with double parathyroid adenomas.
AB  - Severe parathyroid bone disease is a rare clinical presentation of primary
      hyperparathyroidism. Double parathyroid adenomas are even more rare cause of
      primary hyperparathyroidism. The authors present a case of double parathyroid
      adenomas in a 48-year-old man, who presented with painful left lower limb
      swelling, which was slowly growing in size in the last 20 years. Magnetic
      resonance imaging revealed a cystic bony lesion and coincidentally, a urinary
      bladder calculus. Biopsy of the mass revealed giant cell lesion. Laboratory
      investigations showed hypercalcemia and hypophosphatemia with elevated
      parathyroid hormone level. A computerized tomography scan of the neck delineated
      an adenoma of the left superior parathyroid gland, which was surgically removed.
      The left inferior parathyroid was also enlarged and was removed. Histological
      diagnosis confirmed double parathyroid adenomas. The rarity and the interesting
      clinical presentation of such association are discussed.

PMID- 15573207
TI  - Twin intrauterine and cornual gestation in a case of triplet pregnancy.
AB  - Ectopic implantation with in-vitro fertilization-embryo transfer may occur in the
      cornu or tubal stump, which is otherwise rare. Our patient with previous left
      salpingostomy and right salpingo-oophorectomy had 4 embryos transferred through
      in vitro fertilization out of which 3 were successfully implanted with twin
      intrauterine gestation and cornual pregnancy. The cornual pregnancy ruptured at
      12 weeks of gestation and the twin intrauterine pregnancy had a successful
      outcome.

PMID- 15573208
TI  - Combined parathyroid adenoma and an occult papillary carcinoma.
AB  - Although the pathological association of thyroid and parathyroid disease is
      common, the association of both parathyroid adenoma and thyroid cancer is rare.
      We report here a case of a 45-year-old Saudi woman who was diagnosed to have
      primary hyperparathyroidism due to a single parathyroid adenoma as confirmed
      biochemically and radiologically. At operation, the adenoma was found to be an
      intrathyroid and therefore a thyroid lobectomy was performed. Histology of the
      excised lobe revealed in addition to the intrathyroid parathyroid adenoma a
      concurrent occult thyroid papillary carcinoma. This interesting association is
      discussed based on a literature review.

PMID- 15573209
TI  - Primary hyperaldosteronism treated by radiofrequency ablation.
AB  - This is a report of a 57-year-old Jordanian man who had uncontrolled hypertension
      and hypokalemia. He was diagnosed to have primary hyperaldosteronism with left
      adrenal adenoma. Traditionally, surgical resection of the adrenal gland whether
      by laparotomy or laparoscopic procedures would have been considered at this
      point. However, the treating team elected radiofrequency ablation of the left
      adrenal in view of the fact that this facility and the expertise was available in
      the hospital; in addition, this procedure required a shorter duration of
      hospitalization, was less expensive, and was less invasive. Subsequently, the
      patients blood pressure improved to 120/75 mm Hg and his anti-hypertensive
      medications were reduced. Serum aldosterone and computed tomography scan of
      adrenals improved. We are reporting this case as it is the first time such
      modalities in the treatment of adrenal adenoma was used.

PMID- 15573210
TI  - The magnetic resonance image findings of idiopathic granulomatous mastitis.
AB  - Idiopathic granulomatous mastitis is a rare disease of the breast. Clinically and
      radiologically it may mimic breast carcinoma. We report a case of a 34-year-old
      female patient with this diagnosis, concentrating on magnetic resonance image MRI
      findings and its clinical application. There have been other reports on MRI
      findings in this entity in the radiological literature, but in our case report,
      clinical, cytological, pathological, and radiological correlations are also
      provided.

PMID- 15573211
TI  - Exertional dizziness and syncope caused by anomalous left coronary artery origin
      from the right sinus of Valsalva.
AB  - Coronary anomalies are generally rare, but has fascinating congenital cardiac
      disease entities, recognized in less than 1.3% of all coronary angiograms. Left
      coronary artery arising from right sinus of valsalva RSOV represents an extremely
      uncommon subtype. Initial presentations include chest pain, myocardial
      infarction, arrhythmias, sudden death, and rarely exertional syncope. We report a
      case of exertional dizziness and syncope, diagnosed to have anomalous origin of
      left main coronary artery from RSOV. Surgical intervention was curative.

PMID- 15573212
TI  - Clinical and histologic studies of a Qatari family with myofibrillar myopathy.
AB  - The current study reports the first family with confirmed myofibrillar myopathy
      MFM in the Middle East and the third family worldwide. This study highlights the
      importance of considering MFM in young patients presenting with idiopathic
      cardiomyopathy, arrhythmia or atrioventricular block in the Gulf states. This is
      the first report that presented 2 different types of cardiomyopathy and 2
      different indications of permanent pacemaker placement in the same generation of
      a family with MFM. This report studies a Qatari family consisting of one brother
      and 3 sisters. The brother had restrictive cardiomyopathy at the age of 16 years.
      One sister underwent heart transplantation for severe hypertrophic cardiomyopathy
      at the age of 15 years, the other sister had permanent pacemaker for complete
      heart block at the age of 21 years. This report is focused mainly on the clinical
      presentation and investigations carried out for the brother including
      echocardiogram, cardiac catheterization, cardiac and skeletal muscle biopsy, and
      electromyography and electrophysiology studies. The study findings support the
      diagnosis of MFM.

PMID- 15573213
TI  - Bilateral posterior fracture dislocation of the shoulders following seizure.
AB  - Bilateral posterior fracture dislocation is a rare injury known to be associated
      with seizures. Convulsion was found to be the cause of fracture dislocation in
      78% of the cases reported. The mechanism of injury was described by Shaw in 1971.
      The management depends largely on the severity of the injury. In many cases
      reported, the fracture was a large compression defect in the anteromedial aspect
      of the articular surface of the humeral head. It has been suggested that for
      defects that involve less than 20% of the articular surface closed reduction can
      be attempted. Rush nail or percutaneous K wires can be used to maintain
      reduction. Open reduction is necessary for defects that are involving 20-40% of
      the surface. The aim in these cases is to reconstruct the proximal humerus if
      possible by the use of internal fixation. If reconstruction is not feasible, a
      modified McLaughlin procedure can be used to prevent chronic instability of the
      shoulder. This procedure involves re-implanting the subscapularis tendon into the
      defect. Reconstructing fractures that involve more than 40% of the articular
      surface or 4-part fracture is not usually successful. These fractures are
      associated with a high the risk of avascular necrosis. Hemi-arthroplasty or total
      shoulder replacement is generally regarded as better option as they offer rapid
      recovery and eliminate the possibility of multiple procedures if fixation fails.

PMID- 15573214
TI  - A fatal non-01 Vibrio cholerae septicemia in a patient with liver cirrhosis.

PMID- 15573215
TI  - A human fasciolosis presenting with cholelithiasis and choledocholithiasis in
      Van, Turkey.

PMID- 15573216
TI  - A case of a right ovarian artery diverging from a right accessory renal artery.

PMID- 15573217
TI  - Epidermolysis bullosa acquisita and Crohn's disease.

PMID- 15573218
TI  - The dilemma of clinical research. Historical and philosophical considerations of
      physicians' ambitions and patients' fear.

PMID- 15573219
TI  - Authorship. Credit and disputes.

PMID- 15573220
TI  - Gender differences in academic performance among Arab medical students.

PMID- 15573221
TI  - Crossword puzzle. A new paradigm for interactive teaching.

PMID- 15573222
TI  - Trends in women's health in Iran. 1991-2000.

PMID- 15573223
TI  - The effects of melatonin on focal cerebral ischemia-reperfusion model.

PMID- 15573224
TI  - The effect of melathonin on changes in brown and white adipose tissue ratios
      induced by exercise. The significance of age in this effect.

PMID- 15573225
TI  - Embalming with honey.

PMID- 15573226
TI  - Local antigen in serodiagnosis of Trichomoniasis vaginalis.

PMID- 15573227
TI  - Gastric leiomyoma. Is there an association with Helicobacter pylori?

PMID- 15573228
TI  - Do we need blood transfusion in elective infrarenal abdominal aortic aneurysm
      repair.

PMID- 15573229
TI  - Antimicrobial susceptibility patterns of group B Streptococci isolated from
      pregnant women in Trinidad, West Indies.

PMID- 15573230
TI  - Dysregulation of growth hormone in acquired generalized lipodystrophy.

PMID- 15573231
TI  - Evaluation of rheumatoid factor by a new latex enhanced immuno-turbidimetric
      assay.

PMID- 15573232
TI  - Maternal and neonatal outcome of twin pregnancies complicated by a single
      intrauterine dead fetus.

PMID- 15573233
TI  - Radiological features of bisphosphonate therapy in children with osteogenesis
      imperfecta.

PMID- 15573234
TI  - Views of women towards cesarean section.

PMID- 15573235
TI  - Duration of anticoagulation after first episode of unprovoked venous
      thromboembolism.

PMID- 15573236
TI  - Possible herbal treatment for C4HCV patients who are not suitable for interferon
      based treatment.

PMID- 15573237
TI  - Combined sinus tract endoscopy and endoscopic retrograde cholangiopancreatography
      in management of pancreatic necrosis and abscess.
AB  - BACKGROUND: We report our experience of sinus tract endoscopy (STE) and
      endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of
      pancreatic necrosis and abscess. METHODS: Thirteen patients with extensive
      pancreatic necrosis were firstly managed with either percutaneous drainage (PD
      group; n = 9) or open necrosectomy (ON group; n = 4). Debridement of necrotic
      tissue was subsequently performed via the drain tract by STE. ERCP was performed
      only when there was a suspicious of persistent pancreatic duct disruption or
      choledocholithiasis. RESULTS: In the PD group, the median number of STE sessions
      required was 3 (range 2-8). The median hospital and ICU stay were 84 days (range
      29-163 days) and 0 day (range 0-64 days), respectively, with an overall success
      rate of 67%. In the ON group, the median number of STE sessions required was 6.5
      (range 1-18). The median hospital and ICU stay were 82 days (range 58-194 days)
      and 19 days (range 4-24 days), respectively. No mortality or failure was noted in
      the latter group. ERCP was required in nine of 13 patients. CONCLUSION: Combined
      ERCP and STE is a useful adjunct in treating pancreatic necrosis or abscess.

PMID- 15573238
TI  - Endoscopic medial parascapular approach to the thoracic spine.
AB  - BACKGROUND: The traditional endoscopic-assisted approaches to the thoracic spine
      between the 4th and 8th thoracic vertebrae, whether in lateral or prone
      positions, are done ventrolateral to the scapula. Accordingly, the distance
      between the working portal and the spinal target is relatively long, and this
      increases the difficulty of the endoscopic surgery. Exposure of the spinal target
      necessitates excessive retraction and/or deflation of the corresponding lung.
      Both maneuvers are undesirable, particularly in old people with chronic
      obstructive lung disease. METHODS: This paper describes an endoscopic-assisted
      medial parascapular approach in the prone position that offers the surgeon a
      relatively short access to the upper-mid-thoracic spine. Fifteen patients (10 men
      and five women), mean age 68 years, with anterior lesions located between the 4th
      and 8th thoracic vertebrae, constituted this prospective study. The type of the
      anterior endoscopic procedure varied according to the surgical indication and was
      as follows; biopsy from a paravertebral swelling in two patients, debridement and
      fusion in four patients with spondylodiscitis, corpectomy and replacement with
      telescope cage (X-Tenz) in five patients with spinal tumors, corpectomy and
      replacement with X-Tenz in two patients with vertebral osteonecrosis, and
      intersomatic fusion in two patients with fractures. Posterior transpedicular
      fixation was done in 13 patients in the same sitting. RESULTS: Conversion to open
      thoracotomy was not needed. There were no instances of spinal wound infections,
      neurological deficits, dural tears or vascular injuries. Subcutaneous emphysema
      developed in one patient and resolved spontaneously. The mean blood loss was
      1006.7 ml. Neither pseudarthrosis nor metal failure was encountered. The
      segmental kyphotic angle decreased from 13.6 degrees at the preoperative period
      to 9.6 degrees at the immediate postoperative period and reached 11.7 degrees at
      the end of the follow-up. CONCLUSIONS: The endoscopic medial parascapular
      approach, done in the prone position, provides the shortest access to anterior
      spinal lesions between the 4th and 8th thoracic vertebrae. This approach is
      associated with minimal manipulation and retraction of the lung so that a double
      lumen tube is not needed.

PMID- 15573239
TI  - Randomized clinical trial of stapled hemorrhoidectomy vs open with Ligasure for
      prolapsed piles.
AB  - BACKGROUND: The aim of the study was to compare the results in 95 patients
      randomly allocated to undergo either stapled or open hemorrhoidectomy using
      Ligasure. METHODS: Ninety-five patients with grade III and IV hemorrhoids were
      randomly allocated to undergo either stapled (50 patients) or open using Ligasure
      (45 patients). Stapled hemorrhoidectomy was performed with the use of a circular
      stapling device. Open hemorrhoidectomy was accomplished according to the Milligan
      Morgan technique by using Ligasure. Postoperative pain was assessed by means of a
      visual analog scale (VAS). Recovery evaluation included return to pain-free
      defecation and normal activities. A 6-month clinical follow-up and an 18 (12-24)
      month median telephone follow-up were obtained in all patients. RESULTS:
      Operation time for open hemorrhoidectomy using Ligasure was shorter [median 13
      (range 9.2-16.1) min vs 15 (range 8-17) minutes, p < 0.05]. Median range of VAS
      score in the stapled group were significantly lower [VAS score after 8 h: 3 (2-6)
      vs 5 (3-8), p < 0.01; VAS score after first defecation: 5 (3-8) vs 7 (3-9), p <
      0.001. The stapled hemorrhoidectomy was associated with an increased incidence of
      intraoperative bleeding in 18 cases (36%) vs four cases (8.8%) of the Ligasure
      group. There were three cases (6%) from the stapled group with recurrence of the
      hemorrhoids and none from the open technique. CONCLUSIONS: Hemorrhoidectomy with
      a circular stapler device is easy to perform, but one more line of clips must be
      added to the device to avoid intraoperative bleeding from the cut line.
      Hemorrhoidectomy performed using Ligasure is more painful postoperatively but is
      a more radical operation.

PMID- 15573240
TI  - Current use of thromboembolism prophylaxis for laparoscopic cholecystectomy
      patients in Sweden.
AB  - BACKGROUND: The need for thromboembolism (TE) prophylaxis during laparoscopic
      surgery is not well established. The aim of this study was to investigate current
      TE prophylaxis in patients undergoing laparoscopic cholecystectomy (LC) in
      Sweden. METHODS: Mail questionnaire to all Surgical Departments in Sweden about
      the current use of thromboembolism prophylaxis in patients undergoing
      laparoscopic cholecystectomy. RESULTS: The response rate was 78 of 80 departments
      of surgery (98%). Seventy reported performing LC. Thirty-six percent used
      thromboembolism prophylaxis in all patients, 17% in most, 9% in half their
      patients and 39% only rarely. The current use of thromboembolism prophylaxis
      ranged from low-molecular-weight heparin for 7 days + stockings in all patients
      to no prophylaxis at all in the majority of patients. CONCLUSIONS: The use of
      thromboembolism prophylaxis in LC patients is highly variable, even in the small
      and homogenous country of Sweden. Further studies concerning the risk of TE
      complications after laparoscopic surgery are warranted.

PMID- 15573241
TI  - Comparative study of electrothermal bipolar vessel sealer and ultrasonic
      coagulating shears in laparoscopic colectomy.
AB  - BACKGROUND: As an alternative to suture ligatures of the vessels, an
      electrothermal bipolar vessel sealer (EBVS) was recently developed. Meanwhile,
      ultrasonic coagulating shears (UCS) have been widely used clinically to provide
      hemostatic cutting in laparoscopic procedures. We conducted a comparative study
      to investigate the relative advantages of these two instruments. METHODS: The
      study included 30 patients with colon cancer who underwent laparoscopic colectomy
      using either the EBVS or the UCS. We performed a comparative analysis of the
      instruments by viewing videotapes showing their application in laparoscopic
      transverse colectomy and sigmoidectomy. RESULTS: Average patient age was 71.6 +/-
      1.4 years. Average hospital stay was 14.2 +/- 1.0 days. There were no statistical
      differences between the groups in age and hospital stay. The incidence of
      rebleeding was significantly lower in the EBVS group than in the UCS group for
      both surgical procedures (0.3 vs 1.2 in transverse colectomy, 0.3 vs 2.0 in
      sigmoidectomy, respectively). In addition, the required time for mesocolon
      dissection was also significantly shorter when the EBVS was used in both
      laparoscopic transverse colectomy and sigmoidectomy (7.9 vs 18.4, 15.0 vs 27.6,
      respectively). CONCLUSION: The use of the EBVS will enable surgeons to reduce the
      total operating time for laparoscopic colectomy.

PMID- 15573242
TI  - Open vs laparoscopic repair of secondary lumbar hernias: a prospective
      nonrandomized study.
AB  - BACKGROUND: Lumbar hernias are uncommon defects of the posterior abdominal wall.
      Surgical treatment is still controversial in these cases. The aim of this study
      was to compare outcome and costs of the laparoscopic approach vs the open method.
      METHODS: We conducted a prospective nonrandomized study of 16 patients who
      underwent operation for secondary lumbar hernia between January 1997 and January
      2003. Nine were treated via the laparoscopic approach and seven with an open
      technique. The following variables were analyzed: clinical data, hospital data
      (operating time and length of stay), patient comfort (consumption of analgesics
      and time to return to normal activities), and recurrences. Hospital costs were
      also analyzed. RESULTS: There were no differences between the two groups in terms
      of age and history, although the defects of the patients in the laparoscopic
      group were smaller. Mean operating time, postoperative morbidity, mean hospital
      stay, consumption of analgesics, and time to return to normal activities were
      significantly lower in the laparoscopic group (p < 0. 01). No were there any
      statistical differences between the two types of surgical procedure in terms of
      hospital costs. However, the final cost did show differences when expenses for
      readmissions and recurrences were taken into account (p < 0.01). CONCLUSION: The
      laparoscopic approach to secondary lumbar hernia repair is more efficient and
      more profitable than the traditional open technique.

PMID- 15573243
TI  - Biological tissue adhesive for mesh-application in pigs: an experimental study.
AB  - BACKGROUND: Tissue damage during herniotomy may attribute to postoperative
      complications including chronic pain, bleeding and infection. Thus the aim of
      this study was to evaluate a due and simple operative procedure with
      intraperitoneal application of mesh with glue in an experimental model prior to
      use in humans. METHOD: Laparoscopic insertion of a mesh was performed in three
      pigs. The meshes were fixed with a collagen glue. The pigs were sacrificed after
      8 weeks and macroscopic and microscopic evaluation of the meshes, were performed.
      RESULTS: The intraperitoneal placed meshes did not migrate through the study
      period, and there was no sign of inflammation in surrounding tissue or adhesions
      around the meshes. CONCLUSIONS: If these findings can be applied to human
      inguinal herniotomy, this may lead to significant fewer complications including
      development of acute and chronic pain, formation of seroma and infection.
      Furthermore the operation technique is very simple.

PMID- 15573244
TI  - Efficacy of pre-incisional bupivacaine infiltration on postoperative pain relief
      after appendectomy: prospective double-blind randomized trial.
AB  - Pain is the most undesirable and threatening experience for surgical patients.
      This study aims to determine the efficacy of pre-incisional analgesic bupivacaine
      infiltration (preemptive analgesia) on postoperative pain relief after
      appendectomy. A prospective randomized double-blinded study was conducted on 123
      patients aged 13-45 years with a preoperative and-postoperative diagnosis of
      acute appendicitis admitted to Siriraj Hospital, Bangkok, from January to May
      2002. They were randomly set into two groups: the control (61 patients) and the
      preemptive (62 patients). In the preemptive group, bupivacaine (Marcaine) was
      infiltrated into the skin and subcutaneous tissue along the proposed wound line
      before gridiron incision, and also into the muscle layer after incision. The
      control group received no injection. Routine appendectomy was done. Pain score
      was assessed by the patients in the first 48 hr while they were lying supine and
      as they moved to a sitting position at 24 and 48 hr after operation. Morphine
      injection was given on patients' request with pain score = 5 every 4 hr in the
      first 48 hr or until analgesic paracetamol could be taken orally. The pain score
      during the first 6, 12, 24, and 48 hr, including the score while sitting up, were
      all significantly lower ( p < 0.001) in the preemptive group. So were the total
      number of morphine injections and the amount of morphine used postoperatively.
      The pain reduction could be due to interruption of inflammatory or pain mediator
      cascades that normally occur during an operation. This study showed that pre
      incisional bupivacaine infiltration is an effective and simple method of reducing
      postoperative pain for patients undergoing appendectomy.

PMID- 15573245
TI  - Molecular mechanism of c-jun antisense gene transfection in alleviating injury of
      cardiomyocytes treated with burn serum and hypoxia.
AB  - To explore the molecular mechanism of c-jun antisense gene transfection in
      alleviating injury of cardiomyocytes treated with burn serum and hypoxia, burn
      serum was collected from Wistar rats inflicted with 30% third-degree burn of the
      total body surface area. The cardiomyocytes of neonatal Wistar rats were cultured
      and then treated with burn serum and hypoxia (a gas mixture containing 1% O2).
      The constructed c-jun antisense gene recombinant was transfected into the
      cardiomyocytes of neonatal Wistar rats. TdT-mediated d-utp nick end labeling
      (TUNEL) was adopted to examine cardiomyocyte apoptosis. Morphological changes of
      cardiomyocytes were observed under an optic-microscope and an electron
      microscope. Expression of troponin T and beta-tubulin protein, c-jun protein,
      protein kinase Ca (PKCa), and c-jun N-terminal kinase (JNK) were assayed with
      Western blot in the transfected and non-transfected groups. The morphology of
      cardiomyocytes in the non-transfected group changed explicitly, but the change
      was not so obvious in the transfected cardiomyocytes. The expression of beta
      tubulin and troponin increased significantly in the transfected group as compared
      with the non-transfected group. In the non-transfected group, numbers of
      apoptotic cardiomyocytes were significantly higher than in the transfected group.
      The c-jun protein, PKCa, and JNK were significantly expressed in the non
      transfected group, and they reached a maximum at the 24th hour after
      cardiomyocytes were treated with burn serum and hypoxia. In the transfected
      group, however, expressions of c-jun protein, PKCa, and JNK decreased
      significantly compared with the non-transfected group. The c-jun antisense gene
      recombinant transfection alleviates injury to cardiomyocytes treated with burn
      serum and hypoxia, probably through low expression of PKCa and JNK.

PMID- 15573246
TI  - Selective venous sampling in recurrent and persistent hyperparathyroidism:
      indication, technique, and results.
AB  - Between 1992 and 2002, 542 patients underwent a surgical treatment for
      hyperparathyroidism in our department. Twenty-three selective venous sampling
      procedures (SVS) were performed because of the failure of the other methods of
      diagnosis. These patients have recurrent or persistent hyperparathyroidism.
      Noninvasive methods of topographical diagnosis have failed or they have given
      contradictory results. In our experience, the surgeon needs a precise
      localization of the pathological glands in these difficult cases. In our series
      of SVS, specificity was 85.7% and sensitivity was 94.7%. Our results show that a
      high postoperative gradient of parathyroid hormone in the internal thoracic veins
      indicates an ectopic pathological gland in the thymus. A high gradient in a
      vertebral vein indicates a pathological superior parathyroid gland, usually in a
      retro-esophageal position.

PMID- 15573247
TI  - Extended thymectomy in patients with myasthenia gravis with high thoracic
      epidural anesthesia alone.
AB  - Successful extended thymectomy was performed in three patients with myasthenia
      gravis under only high thoracic epidural anesthesia with voluntary breathing. It
      was not necessary to intubate a tracheal tube during operation for any of the
      patients. Neither muscle relaxants nor volatile anesthetic agents were required.
      The mean operating time was 2.0 +/- 0.5 hours. The drainage tubes were removed
      the day after operation in all patients. In two patients the arterial oxygen
      saturation (SaO2) and the arterial partial pressure of carbon dioxide (PaCO2) and
      oxygen (PaO2) were stable; in the third patient the SaO2 was temporarily
      decreased to 92 mmHg when bilateral mediastinal pleura were opened. The right
      pleural defect was then covered with a large wet towel, which was pressed on the
      defect, and thoracic drainage was performed. The left pleural defect was repaired
      with 3-0 Vicryl after suctioning the air in the pleural space, after which the
      SaO2 recovered. All patients were able to drink water and walk within 1 hour
      after the operation. This procedure is advantageous in that the use of muscle
      relaxants and volatile anesthetic agents prevented the laryngeal injury that
      results from translaryngeal intubation; in turn we avoided causing postoperative
      respiratory insufficiency. This may be suitable for the operation of some
      patients with MG, but further studies are required to define the indication.

PMID- 15573249
TI  - Altered serum transforming growth factor-beta1 and monocyte chemoattractant
      protein-1 levels in obstructive jaundice.
AB  - Impaired immune function has long been documented in patients with obstructive
      jaundice, and those with jaundice due to extrahepatic biliary obstruction still
      experience a high rate of postoperative complications and death. Transforming
      growth factor-beta1 (TGFbeta1) appears to be an important regulator of both
      normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1
      (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites.
      We hypothesize that obstructive jaundice may alter serum TGFbeta1 and MCP-1
      expressions in the rat and that oral bile acid or glutamine (or both) can restore
      the altered serum TGFbeta1 and MCP-1 expression in rats with obstructive
      jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four
      groups (n = 10 in each group). Group 1 underwent a sham operation with oral
      normal saline administration. Group 2 underwent common bile duct ligation (CBDL)
      with oral normal saline administration. Group 3 underwent CBDL with oral bile
      acid replacement. Group 4 underwent CBDL with oral glutamine administration.
      Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood
      samples were collected. Serum was obtained after centrifugation for measurement
      of TGFbeta1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum
      TGFbeta1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral
      glutamine administration prevented this elevation, but oral bile acid replacement
      did not. The serum MCP-1 level showed similar changes. After 3 days of
      obstructive jaundice, the TGFbeta1 and MCP-1 levels were altered in the rat. Oral
      glutamine administration, not oral bile acid replacement, was able to prevent
      these alterations.

PMID- 15573250
TI  - Serum hyaluronate level for predicting subclinical liver dysfunction after
      hepatectomy.
AB  - The serum hyaluronate (HA) level reflects sinusoidal endothelial cell function
      correlated with liver function. We have reviewed multiple liver function
      indicators from 37 patients who underwent hepatectomy for various liver diseases.
      The serum HA level was well correlated with the indocyanine green retention rate
      at 15 minutes (ICGR15), lectin-cholesterol (LCAT), hepatocyte growth factor
      (HGF), liver uptake ratio of technetium-99m galactosyl human serum albumin (99mTc
      GSA) at 15 minutes (HH15), prealbumin, and hepatic uptake ratio of 99mTc-GSA at
      15 minutes (LHL15). In addition, the model for end-stage liver disease (MELD)
      score at 7 days after operation was well correlated with serum HA, ICGR15, HH15,
      and LHL15. In patients who showed serum an HA level of = 100 ng/ml before
      hepatectomy, the MELD score had significantly deteriorated by 7 days after
      hepatectomy. Of the 20 patients who showed a serum HA level < 100 ng/ml before
      hepatectomy, 11 had high serum HA after hepatectomy. The bilirubin level 7 days
      after operation in this group was much higher than that for patients who
      maintained a serum HA level < 100 ng/ml after hepatectomy. In addition, the serum
      HGF level before hepatectomy in this group was significantly lower. We concluded
      that the serum HA level is a reliable indicator when evaluating liver function
      and predicting liver dysfunction after hepatectomy. Furthermore, patients with a
      significantly low HGF level who have a normal HA level are susceptible to liver
      dysfunction after hepatectomy.

PMID- 15573251
TI  - Changes in splenic volume during liver regeneration.
AB  - Little is known about the relation between liver regeneration and splenic size.
      We monitored serial changes in liver and spleen volumes using computed tomography
      in 24 patients with biliary cancer who underwent right hepatectomy or more
      extensive liver resection following portal vein embolization (PVE). Nonembolized
      hepatic segments increased in volume from 316 +/- 97 cm3 (34% +/- 8% of total
      liver volume) before PVE to 410 +/- 115 cm3 (44% +/- 8%) after PVE. The volume of
      nonembolized hepatic segments (i.e., remnant liver) increased to 617 +/- 111 cm3
      (59% +/- 10% of total liver volume before PVE) 14 days after hepatectomy and then
      increased slowly to reach 795 +/- 231 cm3 (76% +/- 16%) 1 year after hepatectomy.
      Splenic volume increased from 87 +/- 29 cm3 before PVE to 104 +/- 38 cm3 (119% +/
      17% of original volume) after PVE. Splenic volume increased to 137 +/- 65 cm3
      (155% +/- 40%) by 14 days after hepatectomy and to 155 +/- 67 cm3 (179% +/- 41%)
      by 28 days after hepatectomy, with no further change at 1 year after hepatectomy
      (153 +/- 92 cm3; 174% +/- 79%). The rate of increase in splenic volume within the
      first 14 days after hepatectomy was 2.7 +/- 3.6 cm3/day, correlating well with
      increases in remnant liver volume ( r = 0.64, p = 0.0006). These data indicate
      that the spleen is enlarged during liver regeneration, suggesting that the liver
      and spleen share certain common growth regulatory mechanisms.

PMID- 15573252
TI  - Risk factors for postoperative delirium after liver resection for hepatocellular
      carcinoma.
AB  - We investigated risk factors for delirium in 100 patients who underwent liver
      resection for hepatocellular carcinoma. Postoperative delirium developed in 17
      (17%). Univariate analysis revealed that advanced age (especially = 70 years
      old), a history of smoking, a decreased serum albumin concentration (especially <
      3.8 g/dl), advanced cancer stage (II-IV), major hepatectomy, prolonged operating
      time, and large intraoperative blood loss were possible risk factors for
      postoperative delirium. When patients' preoperative condition and laboratory test
      results were subjected to multivariate analysis, only advanced age [odds ratio
      (OR) 1.201; confidence interval (CI) 1.063-1.357] and a decreased serum albumin
      concentration (OR 0.151; CI 0.025-0.900) were independent risk factors for the
      delirium. The percentages of patients with high aspartate and alanine
      aminotransferase activities, a high indocyanine green retention rate at 15
      minutes, a low platelet count, and advanced cancer stage (II-IV) were higher in
      patients with a low (< 3.8 g/dl), rather than high (= 3.8 g/dl) serum albumin
      concentration. These findings indicate that multiple factors, including advanced
      age, impaired liver function, and advanced cancer stage, affect the development
      of postoperative delirium after liver resection for hepatocellular carcinoma.

PMID- 15573253
TI  - Long-term survival of patients with unresectable colorectal liver metastases
      treated by percutaneous interstitial laser thermotherapy.
AB  - In situ ablation of colorectal cancer (CRC) liver metastases is an accepted form
      of treatment for selected patients. It is associated with low morbidity and
      mortality and increases the number of patients who may benefit from therapy
      compared to resection alone. This study assesses the impact of interstitial laser
      thermotherapy (ILT) on local tumor control and long-term survival in patients
      with unresectable CRC liver metastases. Percutaneous ILT was performed in
      patients with unresectable CRC liver metastases between January 1992 and December
      1999 using a bare-tip quartz fiber connected to an Nd:YAG laser source. This was
      prior to the routine use of a diffusing fiber for ablative therapy. Treatment was
      monitored with real-time ultrasonography. Tumors were considered unresectable
      based on their anatomic location or the extent of liver involvement. Patients
      with extrahepatic disease, more than five liver metastases, or tumors larger than
      10 cm in diameter were excluded from this study. Local tumor control was assessed
      by dynamic computed tomography (CT) 6 months after therapy. Long-term follow-up
      was undertaken, and the impact of various factors on survival was analyzed.
      Eighty patients with a mean age of 63.8 years were suitable for ILT. In total,
      168 liver tumors with a median diameter of 5 cm (range 1-10 cm) were so treated.
      There were no procedure-related deaths. The overall complication rate was 16%,
      with all cases managed conservatively. Bradycardia (n = 5), pneumothorax (n = 3),
      and persistent pyrexia (n = 3) were the most common complications. Complete tumor
      ablation was noted in 67% of patients assessed by CT 6 months following the
      initial therapy. Median follow-up was 35 months (range 4-96 months), with 10
      patients alive at the end of this period. Altogether there were 67 deaths, which
      were related to hepatic disease in 55 cases and to extrahepatic disease in 9;
      they were unrelated to malignancy in 3 others. Three patients were excluded from
      follow-up after ILT down-staging of tumors that allowed complete surgical
      resection. The median disease-free survival of patients treated by ILT was 24.6
      months, with a 5-year survival of 3.8%. Poor tumor differentiation and the
      presence of more than two hepatic metastases were associated with lower overall
      survival (p < 0.01). Fourteen patients treated by ILT for postoperative hepatic
      recurrences had the best outcome, with a median overall survival of 36.3 months
      and a 5-year survival of 17.2%. Percutaneous ILT is a minimally invasive, safe,
      effective technique that appears to improve overall survival in specific patients
      with unresectable CRC liver metastases, compared to the natural history of
      untreated disease reported in the literature.

PMID- 15573254
TI  - Immunohistochemical study of DPC4 and p53 proteins in gallbladder and bile duct
      cancers.
AB  - Gallbladder and bile duct carcinomas belong to the family of biliary tract
      tumors, but they demonstrate different clinical behavior. We evaluated a series
      of biliary tract carcinomas to determine whether they also had genotypic
      differences by analysis of the tumor suppressor genes DPC4 and p53. Twenty-one
      gallbladder cancers, 20 intrahepatic bile duct carcinomas, and 10 extrahepatic
      bile duct carcinomas were retrieved from the surgical pathology files of
      Kaohsiung Medical University Hospital. Sections were immunostained with
      monoclonal antibodies to the DPC4 and P53 proteins. Statistical differences
      between gallbladder cancer and bile duct carcinomas were determined using chi2
      analysis or the Fisher's exact test, when appropriate. Two of the 21 gallbladder
      cancers (9.5%), 7 of the 20 intrahepatic bile duct carcinomas (35%), and five of
      the 10 extrahepatic bile duct carcinomas (50%) were negatively labeled for DPC4.
      The differences were significant between gallbladder carcinoma and both
      intrahepatic bile duct carcinomas (p = 0.023) and extrahepatic bile duct
      carcinomas (p = 0.012). A higher frequency of P53 overexpression was found in
      gallbladder cancers (61.9%) than in intrahepatic bile duct carcinomas (26.3%) (p
      = 0.024). This study suggests that the DPC4 gene may play a limited role in
      gallbladder carcinoma; however, p53 gene mutation is more frequently found in
      gallbladder cancers. In contrast, DPC4 deletion may be more common in bile duct
      carcinomas, especially in those arising from the extrahepatic bile duct. These
      findings support the concept that gallbladder and bile duct carcinomas are
      different tumors with differing etiologies and tumorigenesis.

PMID- 15573255
TI  - Spiegel's lobe bile ducts often drain into the right hepatic duct or its
      branches: study using drip-infusion cholangiography-computed tomography in 179
      consecutive patients.
AB  - Using drip-infusion cholangiography-computed tomography (DIC-CT), we successfully
      identified the bile ducts draining the caudate lobe in 138 of 179 consecutive
      patients with extrahepatic cholelithiasis (179 ducts from Spiegel's lobe and 154
      from the paracaval portion; 1-5 ducts per patient). The dorsal subsegmental duct
      of S8 (B8c) was often identified and could be discriminated from the paracaval
      caudate ducts, thus acting as a landmark for the right margin of the caudate
      lobe. Notably, in more than one-third of the 138 patients, at least one of the
      Spiegel's lobe ducts drained into the right hepatic duct or its branches (30.2%
      of the 179 ducts overall; all ducts joined branches of the right lobe in 25
      patients). Similarly, 34.4% of the 154 paracaval caudate lobe ducts drained into
      the left hepatic duct or its branches. These "anatomical left/right
      dissociations" between the drainage territory and route were much more frequent
      than previously reported. Our results confirm the effectiveness of DIC-CT as a
      classical, noninvasive method for presurgical evaluation of the biliary system,
      but they also suggest that anatomical partial resection of the dorsal liver in
      patients with hilar cholangioma is often impossible because of contralateral
      biliary drainage.

PMID- 15573256
TI  - Resection of the colon simultaneously with pancreaticoduodenectomy for tumors of
      the pancreas and periampullary region: short-term and long-term results.
AB  - Simultaneous resection of the colon with pancreaticoduodenectomy (PD) is
      occasionally inevitable to accomplish curative resection in instances when a
      periampullary tumor involves the mesentery of the colon. However, there is little
      information regarding short- and long-term outcomes of this aggressive surgery.
      Among 95 consecutive patients who underwent PD for periampullary malignant
      tumors, 12 had simultaneous resection of the right colon (group 1) and 83
      underwent PD alone (group 2). Intraoperative variables, postoperative morbidity
      and mortality, and the length of the hospital stay were comparatively analyzed.
      Survival was also compared between the groups in a subset of 36 pancreatic
      adenocarcinoma patients. Group 1 included more patients with pancreatic cancer,
      and portal vein resection was more frequently performed, which seemed to be
      associated with a significantly longer operating time (640 vs. 510 minutes) and
      increased total blood loss (1965 vs. 1220 ml). However, morbidity and mortality
      rates did not differ between the groups (50,0% and 0%, respectively, in group 1;
      44.6% and 1.2%, respectively, in group 2). The median hospital stays were 67 and
      48 days in groups 1 and 2, respectively. In a subset of 36 pancreatic
      adenocarcinoma patients, the median progression-free survivals were 6 months in
      both groups 1 and 2; the median overall survivals were 14 months in group 1 and
      12 months in group 2. There was no statistically significant difference in
      survival between the groups. Simultaneous right hemicolectomy with curative
      intent at the time of PD could thus be performed safely and may offer a survival
      benefit even for individuals who have advanced pancreatic cancers with
      involvement of the transverse mesocolon.

PMID- 15573257
TI  - Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional
      control in patients with primary inoperable pancreatic cancer.
AB  - Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby
      enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and
      toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the
      treatment of patients with locally advanced, unresectable pancreatic cancer. A
      total of 47 patients (29 men, 18 women; median age 61 years) with histologically
      proven advanced pancreatic carcinoma were included in the study. They underwent
      chemotherapy with gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22,
      and 29; concurrent radiation (45-50 Gy) was applied to the tumor and regional
      lymph nodes (1.8-2.0 Gy/fraction 5 days per week). Subsequent to
      chemoradiotherapy, treatment was continued with more two cycles of gemcitabine
      (1000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a 4-week cycle.
      After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete
      response and 23 patients (48.9%) a partial response, for an overall response rate
      of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27
      patients underwent laparotomy. The other 20 patients underwent a definitive
      pancreatic resection. Altogether, 13 patients had negative surgical margins. With
      a median follow-up of 25.7 months (range 12.7-38.7 months) after completion of
      chemoradiation, distant metastasis had occurred in 23 patients and local
      recurrence in only 4 of 44 patients (8.5%). the median progression-free survival
      was 7.8 months (range 6.2-9.4 months). The median survival amounted to 10.7
      months (range 8.4-13.0 months) for all patients, whereas it was prolonged to 24.2
      months (range 6.8-41.7 months) for those undergoing R0 resection. The main
      toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of
      patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11
      patients. We concluded that gemcitabine and cisplatin can safely be combined with
      external beam radiation. This preoperative treatment approach is highly effective
      and appears to improve survival in patients whose tumors are rendered completely
      resectable.

PMID- 15573258
TI  - Decreased identification rate of sentinel lymph node after neoadjuvant
      chemotherapy.
AB  - We prospectively studied the feasibility of sentinel lymph node biopsy (SLNB)
      after neoadjuvant chemotherapy by comparing the identification rate and the false
      negative rate (FNR) with the results obtained from the patients without
      chemotherapy. From October 2001 to March 2003, a total of 284 consecutive
      patients who underwent SLNB and axillary lymph node dissection (ALND) at the
      Center for Breast Cancer, National Cancer Center were enrolled. Of the 284
      patients, 54 underwent neoadjuvant chemotherapy prior to operation. The sentinel
      lymph node (SLN) was mapped by radioactive colloid alone or in combination with
      blue dye. All SLNs were evaluated by 2 mm serial sections after hematoxylin-eosin
      staining. The overall SLN identification rate was 91.9% (261/284): 72.2% (39/54)
      of the patients after chemotherapy and 96.5% (222/230) of the patients without
      chemotherapy. These results suggest that preoperative chemotherapy significantly
      affects lymphatic mapping ( p< 0.001). Among the patients with chemotherapy,
      there were 3 false negatives in 39 successfully mapped tumors, yielding an FNR of
      11.1% (3/27), a negative prediction value (NPV) of 80.0% (12/15), and an accuracy
      of 92.3% (36/39). There were 10 false negatives among 222 successfully detected
      patients without chemotherapy, yielding an FNR of 9.9% (10/101), an NPV of 92.4%
      (121/131), and an accuracy of 95.5% (212/222). These results were not
      statistically different when compared ( p > 0.05). Although the SLN
      identification rate significantly decreased after neoadjuvant chemotherapy, SLNB
      could accurately predict axillary status. Thus SLNB can be an alternative to ALND
      even after neoadjuvant chemotherapy in cases of successful identification of the
      SLN.

PMID- 15573259
TI  - Penetrating cardiac wounds: principles for surgical management.
AB  - Stab wounds are the main type of penetrating cardiac injury in China and they
      have a fairly good prognosis when the patient receives expeditious and
      appropriate management. The objective of this study is to present the experience
      of managing the patients with penetrating cardiac injuries. A retrospective study
      involving 82 cases with penetrating wounds of the heart in the past 16 years was
      carried out. Stab wounds accounted for 86.58% of this series (71 of 82 patients).
      All 82 cases were treated operatively. The amount of preoperative infusion as
      fluid resuscitation for shock was less than 1,000 ml in 65.85% of the present
      study. Only in three patients was preoperative pericardiocentesis performed,
      yielding a false-negative result in one. Six patients sustaining cardiac arrest
      soon after arrival were subjected to emergency room thoracotomy (ERT), and five
      of them survived. The overall survival rate was 96.34%. One patient died of
      exsanguination due to injury of multiple chambers; of the remaining 2 deaths
      after operation 1 was associated with abdominal injuries and the other with
      failure of cerebral resuscitation. From the experience reported in this study,
      early establishment of diagnosis and prompt thoracotomy against time are the
      fundamental factors affecting the outcome of penetrating cardiac injuries.
      Preoperative massive transfusion and pericardiocentesis are not advocated.

PMID- 15573260
TI  - Improved health-related quality of life after coronary artery bypass grafting is
      unrelated to use of cardiopulmonary bypass.
AB  - This prospective study was instituted to assess whether the use of the on-pump
      method or the off-pump method affects changes in health-related quality of life
      (QOL) as evaluated a year after coronary artery bypass graft (CABG) surgery. Data
      including preoperative risk factors and postoperative morbidity up to discharge
      were collected from 508 CABG patients operated in the Heart Center of a
      university hospital and further treated in secondary referral hospitals. Four
      hundred and fifty-two (89.0%) patients underwent operation with the on-pump
      method and 56 (11.0%) with the off-pump method, i.e., without cardiopulmonary
      bypass (CPB). The RAND-36 Health Survey (RAND-36) was used as indicator of QOL.
      The primary outcome measure was a change in the physical component summary (PCS)
      and mental component summary (MCS) from the RAND-36. Symptomatic status was
      estimated according to New York Heart Association (NYHA) class. Assessments were
      made preoperatively and repeated 12 months later. The majority of patients
      operated on-pump (85.6%) and off-pump (92.9%) had a favorable outcome without
      major complications (p = 0.136). The present data showed significant improvement
      (p < 0.001) in all eight domains of QOL following on-pump CABG. Likewise, off
      pump patients improved in all eight aspects, and the change was statistically
      significant in six dimensions. A highly significant (p < 0.001) pattern of change
      was seen in the RAND-36 MCS and PCS scores in both operative groups. Differences
      between the groups were nonsignificant. We conclude that most patients experience
      significant improvement in health-related QOL during the first year after CABG,
      and that cardiopulmonary bypass has no effect on patients' subsequent health
      related QOL, but its use depends on specific indications.

PMID- 15573261
TI  - Coronary bypass before simultaneous pancreas-kidney transplants for type 1
      diabetics in renal failure.
AB  - Our study examined the results of coronary artery bypass (CAB) before
      simultaneous pancreas-kidney (SPK) transplant in type 1 diabetics in renal
      failure. Of 588 pancreas transplant patients from 1992 to 2002, 77 (24 females,
      53 males) were candidates for SPK transplant. All 77 had coronary evaluation and
      were referred for pretransplant CAB. Among the 77 CAB patients, the mean age was
      42 years (range: 30- 63 years), and the duration of diabetes was 28.52 years
      (range: 9-51 years). All had neuropathy, retinopathy, and nephropathy; 12.9% (n =
      10) had angina; and 76% (n = 59) were on dialysis at the time of CAB. The
      creatinine level of the 18 nondialysis patients was 3.7 mg%; 42.8% (n = 33) had
      suffered myocardial infarction. The left ventricular ejection fraction (LVEF) was
      49% (30-65%). At CAB surgery, 88% (n = 68) triple, 9% (n = 7) double, and 2.5% (n
      = 2) single arterial grafts were implanted. All 77 CAB patients had severe
      coronary artery disease (CAD); some vessels could not be bypassed in 9.8%. At
      surgery, 3.4 grafts/patient were implanted (range: 1-6 grafts). All 59 dialysis
      patients continued dialysis after CAB; 6 nondialysis patients required dialysis
      after CAB. The intensive care stay averaged 1.86 days (range: 1-10 days); the
      hospital stay averaged 10.5 days (range 6-28 days). There was no operative
      mortality. Eventually, 68 patients underwent SPK transplant; 9 await organs. The
      waiting period for 68 CAB patients who had SPK was 2 years, 5 months (range: 2
      months to 10 years). The SPK operative mortality was 3.9% (n = 3). Significant
      CAD exists in patients > 30 years of age with type 1 diabetes and renal failure.
      Pretransplant CAB can be done safely and may reduce posttransplant mortality
      associated with cardiac events.

PMID- 15573262
TI  - Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent
      peritoneal carcinomatosis from ovarian cancer.
AB  - Aggressive surgical cytoreduction has been shown to have a positive impact on
      survival of patients with ovarian cancer. After first-line chemotherapy, 47% of
      patients relapse within 5 years, and median survival after second line
      chemotherapy is 10-15 months. Adding intraperitoneal chemohyperthermia (IPCH) to
      surgical cytoreduction could further control ceolomic spread of disease. The aim
      of this study was to determine morbidity and mortality, regional relapse-free
      survival and, preliminarily, overall survival after combining cytoreductive
      surgery with IPCH for the treatment of peritoneal carcinomatosis from ovarian
      epithelial cancer relapsed after prior chemotherapy. Thirty women affected with
      such a relapse were included. Patients underwent extensive cytoreductive surgery
      including tumor resections and peritonectomy, followed by intraoperative IPCH
      with cisplatin. Complete surgical cytoreduction down to nodules less than 2.5 mm
      (CC0-CC1) was obtained in 23 patients (77%). One patient died postoperatively
      from a pulmonary embolism. Major postoperative morbidity was 5/30 (16.7%). We
      registered one case of anastomotic leakage, a spontaneous ileum perforation, a
      postoperative cholecystitis, a hydrothorax, and one patient with bone marrow
      toxicity. Kaplan-Meier estimates of median locoregional relapse-free survival and
      median overall survival were 17.1 months and 28.1 months, respectively. Patients
      with CC0-CC1 had locoregional relapse-free and overall survival rates of 24.4 and
      37.8 months, whereas the remainder had survival rates of 4.1 and 11.0 months. We
      concluded that cytoreductive surgery combined with IPCH is feasible with
      acceptable morbidity and mortality and seems to promise good results in selected
      patients affected with peritoneal carcinomatosis from ovarian cancer.

PMID- 15573263
TI  - Patterns and clinical outcomes associated with routine intravenous sodium and
      fluid administration after colorectal resection.
AB  - Excess intravenous water and sodium may be associated with postoperative
      complications and an adverse outcome. However, the effect of the magnitude of the
      surgery on such a relation has not been studied. This study assesses current
      practice in intravenous fluid and sodium administration after colonic and rectal
      resection and its relation to the postoperative outcome. A series of 100
      consecutive patients undergoing elective colonic (n = 44) or rectal resection (n
      = 56) were included in a retrospective case-cohort study. The volumes of water
      and sodium from intravenous fluid and antibiotic administration on the day of
      surgery and the next 5 days were recorded together with the clinical outcome. The
      mean +/- SEM fluid and sodium administration on the day of operation was greater
      after rectal than colonic resection (4.6 +/- 0.2 vs. 3.6 +/- 0.2 liters and 507
      +/- 34 vs. 389 +/- 22 mmol, respectively (p < 0.05). The mean +/- SEM rate of
      daily fluid and sodium administration for the 5 subsequent days was greater
      following rectal than colonic resection (2.1 +/- 0.1 vs. 1.8 +/- 0.1 L/day and
      155 +/- 8.7 vs. 128 +/- 8.0 mmol/day; p < 0.05). For all resections, there were
      no differences in fluid and sodium administration on the day of surgery in
      patients with or without postoperative complications. During the subsequent 5
      days, patients with complications after colonic resection had a higher
      postoperative mean rate of intravenous sodium administration than those who did
      not (149 +/- 12 vs. 115 +/- 10 mmol; p < 0.05). A similar pattern was not
      observed following rectal resection. Current postoperative intravenous fluid
      prescription delivers approximately 2 liters of fluid and 140 mmol of sodium per
      day. Complications after colonic, but not rectal, resection are associated with
      more early postoperative daily intravenous sodium administration. Because colonic
      resection poses less of a physiologic insult than rectal resection, the overall
      outcome in the former group may be more sensitive to the interplay between fluid
      and sodium overload and patient co-morbidity.

PMID- 15573265
TI  - Laparoscopic cholecystectomy: is it a conscious preference among Turkish patients
      with symptomatic gallstones?--prospective study.
AB  - Laparoscopic cholecystectomy (LC) has the advantages of early return to full
      daily activity, early return to work, and better cosmetic result, as well as
      quickly resolving pain. Yet how this information about the procedure influences a
      patient's attitude toward laparocopy is not known. In this study we analyzed the
      factors that play role in the decision-making process of patients who choose
      laparoscopic surgery, and we also evaluated patients' knowledge of laparoscopy
      and their expectations. A questionnaire was used in evaluating 98 patients
      suffering from symptomatic cholelithiasis scheduled for elective laparoscopic
      cholecystectomy between January 2001 and January 2002. Females constituted 81% of
      the study population. Most of the patients (56%) were housewives. While 45% of
      the patients had an educational status of primary school degree only, 14% had
      graduated from a university. Forty-three patients described their level of
      knowledge about laparoscopy as "low" (had only heard about laparoscopy). In 61%
      of the patients the surgeon was the sole decision maker about the type of the
      operation. Almost none of the patients had a preference for the time of discharge
      from the hospital after surgery, and only three of the actively working patients
      offered a time interval for return to work. From this study we concluded that
      most patients have inadequate information about laparoscopic surgery, that the
      type of operation is dictated mostly by the surgeon, and that early discharge and
      early return to work are not important for many patients.

PMID- 15573266
TI  - Medicine's greatest gifts to surgery.
AB  - Dr. Robert Graves and Dr. Henry Plummer are immortalized by the thyroid diseases
      bearing their names. Dr. Graves' clinical lectures and Dr. Plummer's "goiter
      lunches" were considered medical masterpieces; they introduced novel concepts in
      physical diagnosis that helped surgeons determine when to operate on patients
      with thyrotoxicosis. Dr. Plummer's observations with perioperative iodine
      administration helped lower the mortality associated with thyroidectomy--at that
      time a treacherous operation--to make it one of the safest operations in history.
      Their fascinating discoveries laid foundations for thyroid surgery today. They
      truly are among medicine's greatest gifts to surgery.

PMID- 15573267
TI  - Edoardo Bassini and the wound that inspires.
AB  - Edoardo Bassini, an Italian surgeon active at the turn of the 19th century, made
      a lasting contribution to surgery with his elucidation of the cure for inguinal
      hernia. The magnitude of this contribution in contrast to centuries of
      frustration in attempting surgical repair of hernia is described, as are
      Bassini's personal experiences, which may have played a role in his successful
      search for a cure.

PMID- 15573268
TI  - Jan Mikulicz-Radecki (1850-1905): pioneer of endoscopy and surgery of the
      sinuses, throat, and digestive tract.
AB  - The authors described the medical achievements of Jan Antoni Mikulicz-Radecki--a
      famous surgeon and laryngologist of Polish origin, belonging to the Viennese
      surgical school of Prof. Theodor Billroth at the turn of the 20th century. His
      scientific and clinical activity in Vienna, Cracow, Konigsberg, and Wroclaw
      resulted in 232 publications and several new surgical methods. He changed the
      opinion on scleroma and described benign lymphoepithelial lesions. He was one of
      the authors of modern aseptics, antisepsis in surgery, and is regarded as a
      pioneer of endoscopic procedures. He was interested mainly in thoracic surgery,
      surgery of the abdomen, orthopedics, and laryngology. Mikulicz was the first to
      describe the method of surgical treatment of the maxillary sinus, osteoplastic
      surgery of the nose, esophagoscopy, and lateral pharyngotomy in tonsil carcinoma.
      Prof. Mikulicz was the first to perform thoracic surgery; he performed the first
      pyloroplasty, the first partial esophagectomy and gave rise to antiseptic
      procedures and general surgical management. He described many modifications of
      surgical operations and he constructed the esophagoscope, scoliozymeter, and many
      other useful surgical devices.

PMID- 15573269
TI  - Experiences in applying oxygen therapy in some otolarynological diseases.

PMID- 15573271
TI  - [The era after the "heart valve scandal." The correct and safe use of third party
      funds].

PMID- 15573272
TI  - Ultrastructure of right ventricular myocardium subjected to acute pressure load.
AB  - BACKGROUND: Ultrastructural data on acute right ventricular pressure load in pigs
      are rare. MATERIALS AND METHODS: In control (n = 7) and banding groups (n = 6),
      right ventricular pressure (micromanometry) and function (sonomicrometry) were
      measured. Right ventricular pressure was increased 2.5-fold in the banding group
      by pulmonary artery constriction. Right ventricular biopsies were taken at
      baseline and after 6 h and processed for electron microscopy. Parameters of
      cellular injury were determined stereologically. Three perfusion -fixed hearts
      were investigated qualitatively in each group. RESULTS: Stereology revealed an
      increase in the sarcoplasmic volume fraction and the cellular edema index in the
      banding group ( p < 0.05). Mitochondrial surface-to-volume ratio and volume
      fraction did not show significant alterations. Subendocardial edema and small
      amounts of severely injured myocytes were observed in the perfusion-fixed hearts
      after banding. Ultrastructure was normal in controls. After an initial increase,
      the right ventricular work index declined progressively in the banding group but
      remained unchanged in controls. CONCLUSIONS: Ultrastructural alterations
      resulting from acute right ventricular pressure load were characterized by edema
      of subendocardial myocytes and single cell necrosis. Focal adrenergic
      overstimulation and mechanical stress are probably more relevant in the
      pathogenesis of these lesions than ischemia.

PMID- 15573273
TI  - Changes in sternal blood flow after different methods of internal thoracic artery
      harvesting.
AB  - OBJECTIVE: The study was designed to assess the early changes in sternal
      perfusion after midline sternotomy and different (skeletonized versus
      semiskeletonized) techniques of internal thoracic artery (ITA) harvesting.
      METHODS: The experiments were performed in the swine model. After midline
      sternotomy, ITA harvesting (skeletonized technique) was performed unilaterally in
      Group I (6 animals). The ITA and the internal thoracic vein (ITV) were harvested
      (semiskeletonized technique) in Group II (5 animals). The contralateral sternal
      half served as a control. Using a thermographic camera with a 0.06 degrees C
      sensitivity, sternal perfusion was assessed 2 and 5 hours after surgery. RESULTS:
      Midline sternotomy alone did not affect sternal blood flow. A statistically
      significant ( p < 0.05) reduction in perfusion of the involved sternal half in
      comparison to the control side was detected at 2 and 5 hours after surgery. The
      degree of perfusion deficit was not related to the harvesting technique.
      CONCLUSIONS: Skeletonized and semiskeletonized ITA harvesting techniques caused a
      similar acute reduction in sternal perfusion during the early postoperative
      period and this effect lasted for at least 5 hours.

PMID- 15573274
TI  - Poly-ADP-ribose polymerase inhibition reduces mesenteric injury after
      cardiopulmonary bypass.
AB  - BACKGROUND: We investigated the effects of PARS inhibition on intestinal injury
      in a canine model of cardiopulmonary bypass (CPB). METHODS: Twelve dogs underwent
      90 minutes of hypothermic CPB. 6 dogs received 5 mg/kg PJ34, a selective PARP
      inhibitor during CPB, 6 vehicle-treated animals served as controls. Mesenteric
      blood flow (MBF) and mesenteric vascular resistance (MVR) were measured before
      and 60 minutes after weaning from CPB. Endothelium-dependent vasorelaxation to
      acetylcholine (ACH) and endothelium-independent vasorelaxation to sodium
      nitroprusside (SNP) were expressed as percent change of MVR. In addition,
      mesenteric creatine kinase (CK) and lactate release were determined. RESULTS:
      Baseline hemodynamics, MBF, response to ACH (- 41 +/- 3 vs. - 55 +/- 6 %) and SNP
      (- 60 +/- 2 vs. - 56 +/- 4 %) did not differ significantly between the groups.
      The response to ACH decreased significantly in the control group while it
      remained unchanged in the PJ34 group (- 29 +/- 5 vs. - 46 +/- 9 %, p < 0.05). The
      response to SNP did not change. Mesenteric CK release (325 +/- 99 vs. 16 +/- 10
      U/l, p < 0.05) and lactate production (0.96 +/- 0.17 vs. 0.4 +/- 0.2 mmol/l, p <
      0.05) were significantly lower in the PJ34 group. CONCLUSION: PARP inhibition
      prevents CPB-induced mesenteric endothelial dysfunction and tissue damage.

PMID- 15573275
TI  - Extended myectomy for hypertrophic obstructive cardiomyopathy after failure or
      contraindication of septal ablation or with combined surgical procedures.
AB  - BACKGROUND: Surgical correction of hypertrophic obstructive cardiomyopathy in
      severely symptomatic patients has been proven to be effective over the long term.
      The introduction of catheter-based procedures restricts surgical therapy to a
      subset of patients not suitable for septal ablation or requiring concomitant
      cardiac surgery. METHODS: Between 8/2001 and 8/2003, 25 patients (58 +/- 15
      years) underwent extended transaortic septal myectomy with partial excision and
      mobilization of the papillary muscles. Concomitant surgical procedures were
      performed in 40 % (CABG n = 9, aortic valve replacement n = 2). In 24 %, prior
      septal ablation was ineffective. Intraventricular gradient was 80 +/- 29 mm Hg at
      rest and 143 +/- 35 mm Hg during exercise. Mitral regurgitation affected 72 % of
      patients, and 88 % were NYHA functional class III or IV. RESULTS: No hospital
      death, no postsurgical ventricular septal defect, and no complete
      atrioventricular block occurred. Severe nonfatal complications occurred in 24 %
      of patients. Intensive care was necessary for 1.8 +/- 1.7 days; total hospital
      stay was 11.8 +/- 3.8 days. Early follow-up was complete in 100 % (15 +/- 6
      months, total of 376 months) with no late deaths, no relevant mitral
      regurgitation, or intraventricular gradients. Functional status was markedly
      improved (NYHA class I 40 %, class II 56 %, class III 4 %). CONCLUSIONS: Early
      results of extended surgical myectomy and reconstruction of the subvalvular
      mitral apparatus in hypertrophic obstructive cardiomyopathy remain excellent with
      respect to mortality, morbidity, and functional capacity even when restricting
      surgery to patients earlier supposed to be at high risk.

PMID- 15573276
TI  - Diabetes mellitus in coronary artery surgery: therapeutic strategies in the light
      of recent studies.
AB  - Advances in percutaneous coronary revascularization have meant that,
      increasingly, patients with multivessel diseases are initially treated with the
      methods of interventional cardiology. Ongoing studies involving new stent
      coatings and optimized anti-thrombotic therapies could help to lower future
      restenosis rates and improve the success rate of stenting. Thrombocyte
      glycoprotein IIb/IIIa receptor blockers have already been shown to reduce the
      rate of acute PTCA complications in high-risk patients and could have a sustained
      impact on the long-term prognoses for PTCA patients. However, for diabetic
      patients with coronary multivessel diseases, coronary artery bypass grafting
      using arterial grafts as the initial revascularization method must be given
      preference over other therapy methods. Consequently, this group of patients is
      bound to grow in importance in cardiac surgery. The advances made in percutaneous
      coronary revascularization and in coronary surgery call for further prospective,
      controlled, randomized clinical studies in order to establish the best possible
      treatment strategy for patients with diabetes. It should be noted, however, that
      the therapeutic effect of myocardial revascularization is generally limited to
      individual coronary-arterial segments, whereas the pathological process of
      atherosclerosis is rather diffuse. The surgical strategy should therefore be seen
      as part of an overall strategy which encompasses other forms of treatment (e.g.
      intensive efforts to improve control of blood glucose level, blood pressure, and
      cholesterol level) in order to arrest the general progression of the disease and
      to reduce the risk of myocardial infarction and death.

PMID- 15573277
TI  - Coronary revascularization in DACH: 1991-2002.
AB  - BACKGROUND: The changes in coronary revascularization in Europe in general and in
      the DACH countries (Deutschland, Austria, Switzerland) in particular between 1991
      - 2002 were studied. METHODS: The databases of different national surgical
      societies, registries, and governments and international organizations and
      collegial responses were analyzed. RESULTS: The population of Europe (excluding
      Russia, CIS, and Turkey) increased by 2.29 % from 1991 to 521.84 million in 2002
      and by 4.7 %, 3.4 %, and 7.4 % in Austria (AT), Germany (DE), and Switzerland
      (CH), respectively. The DACH countries contributed 18.76 % to the European
      population in 2002. During this period the cardiac surgery (CS) output increased
      in Europe, AT, DE, CH by 108 % to 428 477 (821/million population), by 72 % to
      7035 (859/million), by 244 % to 125 341 (1521/million), and 61 % to about 8600
      (1175/million), respectively. Coronary artery surgery (CAS) output increased by
      108 % to 241 567 (463/million), by 83 % to 4559 (557/million), by 159 % to 73 929
      (897/million), and by 37 % to about 5000 (684/million), respectively. DACH
      contributed 34.6 % of CAS volume in Europe in 2002. CAS average
      volume/center/year rose from 301 in 1991 to 392 in 2002 in Europe, 312 --> 506 in
      AT, 538 --> 936 in DE, and changed to 331 --> 278 in CH. The percentage of CAS in
      CS hardly changed from 56.2 % in 1991 to 56.4 % in 2002 in Europe but changed
      from 61 % --> 64.8 % in AT, 67.5 % --> 58.98 % in DE, and 68.1 % --> 58.2 % in
      CH. Acceptance of OPCAB remains low at 5 - 18 % of CAS. The increase in
      percutaneous coronary interventions (PCI) volume was more impressive: the 2002
      average of PCI/million was 1244 in Europe, 1659 in AT, 2524 in DE, and 1708 in
      CH; 36 % of the total number of European PCI was done in DACH. In 2002, coronary
      stenting was done in 83 % of PCI in Europe: with 1039/million in Europe,
      1399/mill (84 %) in AT, 1994/mill (79 %) in DE, and 1435/mill (84 %) in CH. The
      average European total coronary revascularization activity (PCI + CAS) increased
      from 1991 by 257 % to 1707/million in 2002; in DACH it increased by 261 % to
      3243/million. CONCLUSIONS: Coronary revascularization productivity in Europe
      during the last decade has continued to grow (mostly in the PCI sector) but has
      lagged behind that in the USA. The pattern of coronary artery surgery remains
      fairly consistent in DACH while CAS productivity is far ahead of the rest of
      Europe despite recent plateauing. The trend towards PCI was equally pronounced in
      AT, DE, and CH.

PMID- 15573278
TI  - Appropriateness of invasive cardiovascular interventions in German hospitals
      (2000-2001): an evaluation using the RAND appropriateness criteria.
AB  - OBJECTIVE: Germany has the highest per capita rate of percutaneous transluminal
      coronary angioplasties (PTCAs) in Europe and the third highest per capita rate of
      heart surgeries requiring a heart-lung machine. The goal of this study was to
      evaluate the appropriateness of PTCA, coronary artery bypass graft (CABG), and
      carotid endarterectomy (CEA) in German hospitals using RAND appropriateness
      criteria. METHODS: A retrospective study in 121 randomly selected German
      hospitals (52 % of all hospitals contacted) was performed from December 2000 to
      August 2001. A total of 361 patients were enrolled providing information on the
      appropriateness of 128 PTCAs, 92 CABGs, and 141 CEAs. RESULTS: Inappropriateness
      rates were 2 % (95 % CI 0 - 5 %), 4 % (95 % CI 1 - 9 %), and 3 % (95 % CI 1 - 7
      %) for PTCA, CABG, and CEA, respectively. The overall rate of uncertain
      procedures was 42 % (95 % CI 36 - 47 %). Only 38 % (95 % CI 32 - 45 %) of
      patients who received a coronary intervention had had a pre-interventional stress
      test. CONCLUSIONS: The study yielded little overt overuse in the performance of
      PTCAs, CABGs, and CEAs, but potentially large underuse of stress tests. Despite a
      high per capita rate of invasive cardiovascular interventions in Germany, the
      rate of inappropriate procedures was not larger than in other countries.

PMID- 15573279
TI  - Appropriateness of invasive cardiovascular interventions in German hospitals
      (2000-2001): an evaluation.

PMID- 15573280
TI  - Off-pump ascending to descending aorta bypass grafting with descending aneurysm
      exclusion.
AB  - We performed an ascending to descending aorta bypass grafting with exclusion of
      the descending thoracic aortic aneurysm through a median sternotomy incision
      without cardiopulmonary bypass in a patient with severe chronic obstructive
      pulmonary disease. The patient was a 75-year-old man who had undergone
      endovascular stent-graft placement for a descending thoracic aortic aneurysm. The
      operation became necessary because the aneurysm continued to expand without
      evidence of endoleak. The postoperative course was uneventful, and without
      respiratory morbidity.

PMID- 15573281
TI  - Leiomyosarcoma--an unusual cause of right ventricular outflow tract obstruction.
AB  - A 76-year-old female patient was admitted with progressive dyspnea on exertion,
      signs of right ventricular failure, and severe pulmonary stenosis.
      Intraoperatively an infiltrating right ventricular outflow tract (RVOT) tumor was
      found and xenograft conduit replacement was performed successfully. Histological
      examination revealed primary cardiac leiomyosarcoma, the patient was discharged
      and is in good health condition at 9 months' follow-up. Unusual causes of RVOT
      obstruction should be considered.

PMID- 15573282
TI  - Right ventricular assist device implantation--a new transcutaneous approach.
AB  - The necessity for a secondary right heart assist device (RVAD) is a disastrous
      complication in left ventricular assist device (LVAD) support with respect to
      both complications and outcome. We have developed a new technique for inflow and
      outflow cannulation via a transcutaneous cannula in the femoral vein and a
      prosthesis-supported arterial cannula into the pulmonary artery, which does not
      necessitate rethoracotomy for device explantation. In addition to the simplified
      RVAD removal this transcutaneous approach may reduce the complications in
      patients requiring RVAD support.

PMID- 15573283
TI  - [Application of multislice spiral CT (MSCT) in multiple injured patients and its
      effect on diagnostic and therapeutic algorithms].
AB  - The initial diagnostic work-up of trauma victims with multiple injuries is
      currently a combination of conventional radiography (CR), ultrasound (US), and
      computed tomography (CT). This article reviews the diagnostic quality of the
      different imaging modalities regarding detection and classification of injuries.
      CT performs better than US in detecting traumatic lesions of abdominal
      parenchymal organs. Furthermore, CT is better than CR in detecting
      therapeutically relevant chest and bone injuries. MSCT may replace CR and US
      under the condition that it is faster than or at least as fast as the
      conventional approach to diagnose life threatening injuries. This can be achieved
      only by changing the work-flow for the entire trauma team including radiologist.
      Furthermore, certain prerequisites must be fulfilled including integration of a
      MSCT scanner into the emergency room. An optimized whole body CT protocol for the
      assessment of trauma victims using MSCT as well as a two-step algorithm for
      reporting the imaging findings depending on their clinical significance is
      presented.

PMID- 15573284
TI  - [Does magnetization transfer ratio (MTR) contribute to the diagnosis and
      differential diagnosis of the dementias?].
AB  - PURPOSE: The magnetization transfer ratio (MTR) is a MR-based neuroimaging
      procedure aiming at the quantification of the structural integrity of brain
      tissue. Its contribution to the differential diagnosis of dementias was examined
      and discussed in relation to the pathogenesis of age-related dementias. MATERIALS
      AND METHODS: Sixty-one patients from a memory clinic were diagnosed by general
      physical and neuropsychiatric examination, and underwent neuropsychologic testing
      and neuroimaging using MRI. Their clinical diagnoses were based on standard
      operational research criteria. Additionally, the MTR in 10 defined regions of
      interest (ROI) was determined. This investigation was performed using a T1
      weighted SE sequence. Average MTR values were determined in the individual ROI
      and their combinations and correlated with the age, gender, cognitive impairment
      and clinical diagnosis. Sensitivity, specificity, positive and negative
      predictive value were determined, as well as the rate of correct classifications.
      RESULTS: For cognitive healthy subjects, the MRT values correlate only mildly,
      though significantly, with age in the hippocampus and with gender in the dorsal
      corpus callosum. In contrast, the MTR in the frontal white matter correlates
      strongly and highly significantly with cognitive impairment in patients with
      dementia. The differential diagnostic assignment of Alzheimer's disease versus
      vascular dementia by MTR provides a correct classification of approximately 50 %
      to 70 %. PPV for no dementia vs. vascular dementia or the NPV for vascular vs.
      Alzheimer's disease are considerably higher exceeding 80 %. For no dementia vs.
      Alzheimer's disease, the NPV was over 90 %. CONCLUSION: MTR values indicate
      functional changes in the brain tissue between cognitive healthy and demented
      patients, and correlate with the cognitive loss, but not with age and gender. In
      principle, the MTR is suitable for the diagnosis of age-related dementias, but
      does not contribute substantially to the differential diagnosis of vascular
      dementia vs. Alzheimer's disease. The present results support the assumption of a
      synergy between vascular and degenerative components of age-related dementias.

PMID- 15573285
TI  - [Diagnostic imaging of hilar cholangiocarcinoma: preoperative evaluation of ERC,
      MRC and PTC in comparison with histopathology].
AB  - PURPOSE: To compare the results of the preoperative workup consisting of
      endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography
      (MRC), and percutaneous resonance cholangiography (PTC) with the tumor extent of
      the surgical specimen in patients with hilar cholangiocarcinoma (hilCC).
      MATERIALS AND METHODS: Between 9/1997 and 12/2002, 59 patients with hilCC tumor
      underwent surgical resection. Preoperative ERC, MRC, and PTC were analyzed,
      blinded for the identity of the patient, and compared with the surgical specimen.
      For this retrospective analysis, 55 of the initial 59 ERCs, 39 of the initial 40
      MRCs and 32 of the initial 38 PTCs were available. Most of the ERCs and MRCs had
      been performed at referring institutions by various investigators. In 20
      patients, all three imaging modalities were available for direct comparison.
      RESULTS: The mean scores of the visualization of the bile ducts and tumor differ
      considerably for ERC, MRC and PTC, with PTC visualizing the bile ducts better
      than ERC (p < 0.001) and MRC (p = 0.019). The tumor classification according to
      Bismuth and Corlette was correctly predicted by ERC in 29 %, by MRC in 36 % and
      by PTC in 53 %. The tumor extent was overestimated in 40 % (ERC), 41 % (MRC) and
      31 % (PTC) and underestimated in less than 10 % for all modalities. Twenty
      patients, who underwent all three imaging modalities, were included in an
      additional analysis for a direct comparison of ERC, MRC and PTC. PTC provided
      correct or acceptable information on tumor extent in 19 of 20 patients, MRC in 15
      of 20 patients, and ERC in only 11 of 20 patients. The statistical analysis
      revealed a significant superiority of PTC to ERC (McNemar test: p < 0.01) but not
      to MRC (p = 0.22). DISCUSSION: The management of patients with hilar
      cholangiocarcinoma requires a high degree of expertise in diagnostic imaging
      techniques. Cholangiography should not only define the location but also
      visualize the uppermost extent of the tumor to determine resectability. In
      contrast to most reports in the literature, ERC and MRC were found to be of
      limited reliability regarding the assessment of the tumor extent. ERC may be more
      and more reserved for patients considered for nonsurgical intervention or
      palliation. PTC proved to be the most reliable approach. MRC represents a
      noninvasive diagnostic tool for the evaluation of malignant perihilar biliary
      obstructions, but should be performed at highest quality using state-of-the-art
      MRI techniques. The most common mistake of each diagnostic modality was an
      overestimated tumor extent, which may exclude patients from potentially curative
      surgery.

PMID- 15573286
TI  - [Computer-aided segmentation, form analysis and classification of 2975 breast
      microcalcifications using 7-fold microfocus magnification mammography].
AB  - PURPOSE: To classify mammary microcalcifications for the prediction of malignancy
      by using computer-aided analysis of morphometric characteristics. MATERIALS AND
      METHODS: Seven-fold microfocus magnification radiography (direct magnification)
      was performed on 2975 paraffin embedded microcalcifications. After digitization
      of the radiographic films and segmentation of the microcalcifications, the
      morphometric characteristics, such as circumference, surface and polar
      transformation with determination of the greatest and smallest radius, were
      measured. Using the classification and regression tree (CART) statistical
      analysis program, the calcifications were classified by computer on the basis of
      the morphometric characteristics and the known histological result. RESULTS:
      Benign conditions were essentially represented by small round calcifications with
      a greatest radius of < or = 114.2 microm, a smallest radius of > 18.5 microm and
      a circumference of < or = 462.3 microm. Using > 70 % microcalcifications
      classified in a patient by the computer as "malignant," CART increases the
      frequency of malignant conditions, with the diagnostic separation between benign
      and malignant at an Az value (surface below the ROC curve) of 0.7863. CONCLUSION:
      A computer-assisted classification of individual microcalcifications on the basis
      of morphometric characteristics can supplement the information for a computer
      assisted mammographic diagnosis (CAD).

PMID- 15573287
TI  - [Consensus double reading of mammograms in private practice].
AB  - PURPOSE: To evaluate retrospectively the results of consensus double reading of
      mammograms in a private practice for a period of 1.5 years (November 2001 to
      March 2003). MATERIALS AND METHOD: Two independent experts with dedicated
      training read all mammograms on a weekly basis. All mammograms including
      sonographic examinations were evaluated independently and categorized using the
      BI-RADS classification. The achieved consensus included a possible recommendation
      for recall or therapy. A total of 3936 mammograms and 1912 sonography studies
      were evaluated. All cases with BI-RADS 4 and 5 categories were compared with the
      histologic results. For a period of three months, the acceptance of double
      reading including a delay of the final report by one week was tested with a
      questionnaire and informed consent sheet. RESULTS: BI-RADS categories 4 and 5
      were found in 57 cases, with 41 consensus results by two independent readers and
      26 carcinomas verified by histology. No consensus could be reached in 16
      patients, of which 10 had a final histologic result, with 5 benign lesions and 5
      carcinomas of less than 1 cm in diameter. Clinical symptoms or alterations were
      absent in all patients. The 5 carcinomas were discovered by the double reading
      procedure. The result of the questionnaire (695 questionnaires) showed a refusal
      rate of 0.7 %, with only 5 women refusing the opportunity of double reading their
      mammograms. CONCLUSION: Double reading of mammograms by independent experts is
      feasible, shows a measurable increase in quality and is accepted by almost all
      women.

PMID- 15573288
TI  - [Direct CT-arthrography versus direct MR-arthrography in chronic shoulder
      instability: comparison of modalities after the introduction of multidetector-CT
      technology].
AB  - PURPOSE: To evaluate the diagnostic accuracy of direct multidetector CT
      arthrography (CTA) and direct MR arthrography (MRA) in patients suffering from
      chronic shoulder instability. MATERIALS AND METHODS: Twenty-nine patients
      suffering from chronic shoulder instability were included into a prospective
      study. In all cases, the indication for direct CTA and arthroscopy was set by the
      orthopedic surgeon. Prior to the imaging procedures, 10 to 20 ml of a special
      combination of contrast media (including saline, Isovist(R) and Magnevist(R) in a
      relation of 125 : 125 : 1) was injected into the joint under sterile conditions.
      First, CTA was performed with a multidetector CT, with images reconstructed in
      the axial, semi-coronal and semi-sagittal planes. Thereafter, MRA was performed.
      Axial images were obtained using a T1-weighted, fat-saturated spin echo sequence
      and semi-coronal images using a T1-weighted FLASH-3D GRE sequence. The results of
      CTA and MTA were compared with results obtained from arthroscopy or arthrotomy.
      RESULTS: MRA was superior to CTA in the detection of labral lesions. The
      sensitivity of MRA was 96 % and the specificity 96 %, compared to a sensitivity
      of 76 % (p < 0.05) and specificity of 92 % for CTA. Both methods showed the same
      effectiveness concerning the assessment of capsule distension (sensitivity for
      both techniques: 91 %). CONCLUSIONS: MRA seems to be superior to CTA in the
      diagnostic workup of chronic shoulder instability even when using a multidetector
      CT technique.

PMID- 15573289
TI  - [MRI monitoring of autologous hyaline cartilage grafts in the knee joint: a
      follow-up study over 12 months].
AB  - PURPOSE: To evaluate the suitability of different MR sequences for monitoring the
      stage of maturation of hyaline cartilage grafts in the knee joint and the early
      detection of complications like hypertrophy. In addition, it was analyzed whether
      indirect MR arthrography can indicate debonding of the graft. MATERIALS AND
      METHODS: MRI examinations were performed in 19 patients, aged 17 - 48 years, with
      autologous transplantation of a hyaline cartilage tissue graft after knee trauma.
      Examination dates were prior to transplantation to localize the defect, and 6
      weeks, 3, 6 and 12 months after transplantation to control morphology and
      maturation of the autologous graft. Standard T2- and proton-density-weighted
      turbo spin echo (TSE) sequences and T1-weighted spin echo (SE) sequences were
      used, as well as gradient echo (GRE) sequences with and without magnetization
      transfer (MT) prepulses. In some cases, indirect MR arthrography was performed.
      RESULTS: Cartilage defect and the hyaline cartilage graft could be detected in
      all 19 patients. Hypertrophy of the graft could be found early in 3 patients and
      debonding in 1 patient. For depicting the graft a short time after surgery, T2
      weighted TSE-sequences showed the best results. Six and 12 months after
      transplantation, spoiled 3D-GRE-sequences like FLASH3D (fast low angle shot)
      showed reduced artifacts due to magnetic residues from the surgery. Difference
      images from GRE-sequences with and without MT pulse provided high contrast
      between cartilage and surrounding tissue. The quantification of the MT effect
      showed an assimilation of the graft to the original cartilage within 12 months.
      Indirect MR arthrography showed subchondral contrast medium even 12 months after
      transplantation in 3 patients. CONCLUSION: MRI allows a reliable depiction of the
      hyaline graft and provides very early detection of complications like
      hypertrophy. The MT effect seems to be correlated with maturation of the graft
      and allows selective depiction of normal cartilage and engrafted cartilage.

PMID- 15573290
TI  - [Assessment of global and regional left ventricular function with a 16-slice
      spiral-CT using two different software tools for quantitative functional analysis
      and qualitative evaluation of wall motion changes in comparison with magnetic
      resonance imaging].
AB  - PURPOSE: To determine global and regional left ventricular (LV) function from
      retrospectively gated multidetector row computed tomography (CT) by using two
      different semiautomated analysis tools and to correlate the results with those of
      magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nineteen patients (5
      females, 14 males, mean age 69 years) underwent 16-slice spiral-CT (MS-CT) with
      standard technique without administration of beta-blockers for a decrease in the
      cardiac rate. Ten series of images were reconstructed at every 10 % of the RR
      interval. With commercially available software capable of semiautomated contour
      detection, end-diastolic and end-systolic LV volumes (EDV and ESV) were
      determined from short-axis multiplanar CT reformations (MPR). Axial images of the
      end-systolic and end-diastolic cardiac phase were transformed to 3D volumes (3D)
      to determine EDV and ESV by using a threshold-supported reconstruction algorithm
      dependent on the contrast enhancement of the left ventricle. Steady-state free
      precession cine MR images were acquired in short-axis orientation on the same day
      in all but one patient. Regional wall motion was assessed qualitatively in 17
      left ventricular segments and classified as normo-, hypo-, a- or dyskinetic.
      Bland-Altman analysis was performed to calculate limits of agreement and
      systematic errors between CT and MRI. RESULTS: For MPR/3D, mean end-diastolic
      (144.4/142.8 mL +/- 67.5/67.1) and end-systolic (66.4/68.7 mL +/- 52.1/49.9) LV
      volumes as determined with MS-CT correlated well with MRI measurements (147.6 mL
      +/- 67.6 [ r = 0.98/0.96] and 73.3 mL +/- 55.5 [ r = 0.98/0.98], respectively [ p
      <.001]). LV stroke volume (77.6/74.1 +/- 19.2/23.4 mL for CT vs. 74.4 mL +/- 18.4
      for MRI, r = 0.92/0.74) and LV ejection fraction (58.6/55.9 % +/- 13.5/13.7 for
      CT vs. 55.6 % +/- 13.5 for MRI, r = 0.95/0.91) also showed good correlation (p
      <.001). Regional wall motion analysis revealed agreement between CT and MRI in
      316/323 (97.8 %) myocardial segments. CONCLUSION: Semiautomated analysis of 16
      detector row CT data sets enables global and regional volumetric and functional
      analysis. The CT results correlate well with MRI findings for short axis MPR and
      for 3D volume reconstructions, with a higher statistical spread for the 3D
      method. The underestimation of end-systolic and end-diastolic volumes with CT may
      be caused by partial volume averaging due to the lower temporal resolution as
      compared with MRI.

PMID- 15573291
TI  - [Long-term results of interventional treatment of large unresectable
      hepatocellular carcinoma (HCC): significant survival benefit from combined
      transcatheter arterial chemoembolization (TACE) and percutaneous ethanol
      injection (PEI) compared to TACE monotherapy].
AB  - PURPOSE: A retrospective analysis of long-term efficacy of combined transcatheter
      arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and
      TACE monotherapy was conducted in patients with large, non-resectable
      hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Fifty patients with large,
      unresectable HCC lesions underwent selective TACE. Liver cirrhosis was present in
      42 patients, due to alcohol abuse (n = 22) and viral infection (n = 17). In three
      patients, the underlying cause for liver cirrhosis remained unclear. Child A
      cirrhosis was found in 22 and Child B cirrhosis in 20 patients. Repeated and
      combined TACE and PEI were performed in 22 patients and repeated TACE monotherapy
      was performed in 28 patients. Survival and complication rates were determined and
      compared. RESULTS: The 6-,12-, 24- and 36-month survival rates were 61 %, 21 %, 4
      %, and 4 % for TACE monotherapy and 77 %, 55 %, 39 % and 22 % for combined TACE
      and PEI (Kaplan-Meier method). The kind of treatment significantly affected the
      survival rate (p = 0.002 log-rank test). Severe side effects were present in two
      patients of the monotherapy group and in three patients of the combination
      therapy group. CONCLUSION: The combination of TACE and PEI is an effective and
      safe method in the palliative treatment of large HCC that has the potential of
      improving long term survival compared to TACE monotherapy.

PMID- 15573292
TI  - Performance evaluation of a 64-slice CT system with z-flying focal spot.
AB  - The meanwhile established generation of 16-slice CT systems enables routine sub
      millimeter imaging at short breath-hold times. Clinical progress in the
      development of multidetector row CT (MDCT) technology beyond 16 slices can more
      likely be expected from further improvement in spatial and temporal resolution
      rather than from a mere increase in the speed of volume coverage. We present an
      evaluation of a recently introduced 64-slice CT system (SOMATOM Sensation 64,
      Siemens AG, Forchheim, Germany), which uses a periodic motion of the focal spot
      in longitudinal direction (z-flying focal spot) to double the number of
      simultaneously acquired slices. This technique acquires 64 overlapping 0.6 mm
      slices per rotation. The sampling scheme corresponds to that of a 64 x 0.3 mm
      detector, with the goal of improved longitudinal resolution and reduced spiral
      artifacts. After an introduction to the detector design, we discuss the basics of
      z-flying focal spot technology (z-Sharp). We present phantom and specimen scans
      for performance evaluation. The measured full width at half maximum (FWHM) of the
      thinnest spiral slice is 0.65 mm. All spiral slice widths are almost independent
      of the pitch, with deviations of less than 0.1 mm from the nominal value. Using a
      high-resolution bar pattern phantom (CATPHAN, Phantom Laboratories, Salem, NY),
      the longitudinal resolution can be demonstrated to be up to 15 lp/cm at the
      isocenter independent of the pitch, corresponding to a bar diameter of 0.33 mm.
      Longitudinal resolution is only slightly degraded for off-center locations. At a
      distance of 100 mm from the isocenter, 14 lp/cm can be resolved in the z
      direction, corresponding to a bar diameter of 0.36 mm. Spiral "windmill"
      artifacts presenting as hyper- and hypodense structures around osseous edges are
      effectively reduced by the z-flying focal spot technique. Cardiac scanning
      benefits from the short gantry rotation time of 0.33 s, providing up to 83 ms
      temporal resolution with 2-segment ECG-gated reconstruction.

PMID- 15573293
TI  - [Clinical use of digital retrospective image fusion of CT, MRI, FDG-PET and SPECT
      -- fields of indications and results].
AB  - PURPOSE: To evaluate the feasibility and the clinical benefits of retrospective
      digital image fusion (PET, SPECT, CT and MRI). MATERIALS AND METHODS: In a
      prospective study, a total of 273 image fusions were performed and evaluated. The
      underlying image acquisitions (CT, MRI, SPECT and PET) were performed in a way
      appropriate for the respective clinical question and anatomical region. Image
      fusion was executed with a software program developed during this study. The
      results of the image fusion procedure were evaluated in terms of technical
      feasibility, clinical objective, and therapeutic impact. RESULTS: The most
      frequent combinations of modalities were CT/PET (n = 156) and MRI/PET (n = 59),
      followed by MRI/SPECT (n = 28), CT/SPECT (n = 22) and CT/MRI (n = 8). The
      clinical questions included following regions (more than one region per case
      possible): neurocranium (n = 42), neck (n = 13), lung and mediastinum (n = 24),
      abdomen (n = 181), and pelvis (n = 65). In 92.6 % of all cases (n = 253), image
      fusion was technically successful. Image fusion was able to improve sensitivity
      and specificity of the single modality, or to add important diagnostic
      information. Image fusion was problematic in cases of different body positions
      between the two imaging modalities or different positions of mobile organs. In
      37.9 % of the cases, image fusion added clinically relevant information compared
      to the single modality. CONCLUSION: For clinical questions concerning liver,
      pancreas, rectum, neck, or neurocranium, image fusion is a reliable method
      suitable for routine clinical application. Organ motion still limits its
      feasibility and routine use in other areas (e. g., thorax).

PMID- 15573294
TI  - [Digital knowledge in the coat pocket -- hand-held personal digital assistants in
      radiology].
AB  - The personal digital assistant (PDA) enables the independent access to large data
      in a pocket-sized format. The applications for hand-held computers are growing
      steadily and can support almost any kind of problem. An overview of the available
      hardware and software is provided and evaluated. Furthermore, the use of the PDA
      in the clinical daily routine is described. In view of the numerous software
      programs available in radiology, the range of software solutions for radiologists
      is presented. Despite the high acquisition cost, the PDA has already become the
      digital assistant for the radiologist. After a short time of getting used to the
      PDA, nobody wants to miss it at work or at home. New technical features and
      available software programs will continuously increase the integration of the PDA
      into the medical workflow in the near future.

PMID- 15573295
TI  - [Intravenous contrast medium application in elderly patients -- evaluation of
      Iopentol (Imagopaque 300)].
AB  - PURPOSE: We examined the subjective compatibility of elderly patients who
      received the intravenous contrast medium Iopentol (Imagopaquetrade mark 300). In
      addition, objective data were aquired to show possible interactions between
      contrast media and organ systems in old patients. METHODS AND MATERIALS: A CT
      scan with intravenous application of contrast media was performed on 132 patients
      ranging in age from 75 to 96 years. The patients were questioned about their
      individual sensations. In addition, blood pressure, creatinine and CT
      densitometry were acquired as objective data. RESULTS: The patients' individual
      sensations and clinical data show a very low rate of complications. Mild allergic
      reactions were noticed in two patients. No severe anaphylactic reactions were
      encountered. Statistically significant changes in blood pressure before and after
      administration of the contrast medium were not observed. The serum creatinine
      concentration was unchanged after application of contrast media. For CT
      densitometry, the patients were divided into two groups, one group with patients
      75 - 84 years and the other group with patients 85 - 96 years of age. CT
      densitometry showed no age-related differences. The protocol of contrast
      administration resulted in excellent opacification of the examined regions, only
      the liver did not enhance in some cases before the opacification of the portal
      vein. CONCLUSION: It is shown that old age alone is no reason to withhold
      contrast media containing iodine when performing CT. For the evaluation of the
      liver, however, the peculiarities of old age have to be taken into account and
      the interval between injection of the contrast medium and beginning of the spiral
      CT has to be extended.

PMID- 15573296
TI  - [Automatic injectors in magnetic resonance imaging and computed tomography: pilot
      study on hygienic aspects].
AB  - PURPOSE: To evaluate hygienic conditions using automatic injectors in magnetic
      resonance imaging (MRI) and computed tomography (CT) during clinical routine.
      MATERIALS AND METHODS: The surfaces of medical devices (e. g., control console)
      and the palms of the technical and medical staff were microbiologically analyzed
      by taking imprints before and after hygienic education. In addition, the injector
      syringes for contrast medium (CM) and saline were checked for microbiological
      contamination following multiple (MRI: 14 h; CT 8 h) and single use. Furthermore,
      the potential of retrograde contamination from the patient along the tube was
      analyzed. RESULTS: A bacterial contamination with typical dermal bacteria was
      documented for the surfaces of the medical devices, the palms of the technical
      and medical staff, and the injection syringes following multiple use (MRI: 10/10
      CM syringes, 6/10 saline syringes; CT: 8/10 CM syringes, 5/10 saline syringes).
      Correct hand disinfection in combination with single use of syringes avoided
      bacterial colonization. Retrograde bacterial contamination from the patient was
      not observed. CONCLUSION: Regular hygienic teaching sessions for technical and
      medical staff in MRI and CT departments using automatic injectors should be
      mandatory. Furthermore, the multiple use of syringes should be avoided until
      investigations addressing the potential of bacterial contamination are performed.

PMID- 15573297
TI  - [Imaging of the abdominal wall: combination of tissue-harmonic-imaging and
      extended field-of-view sonography].
AB  - PURPOSE: To evaluate the combined use of extended field-of-view sonography and
      tissue harmonic imaging (THI) for assessment of the abdominal wall. MATERIALS AND
      METHODS: In 32 patients (25 patients without and 7 patients with abdominal wall
      pathologies) extended field-of-view sonography of the abdominal wall was
      performed with and without THI using a 7.5 MHz ultrasound transducer. Images with
      a scan length of 60 cm were acquired above and below the arcuate line. The images
      were independently assessed by two observers regarding visibility of the anatomic
      structures and delineation of pathological changes using a 4-point grading scale.
      Furthermore, the influence of the extent of the subcutaneous fat on the image
      quality was assessed. For statistical analysis, kappa coefficients, Fisher"s
      exact test and a repeated measurement analysis of variance (ANOVA) were applied.
      RESULTS: In all patients, delineation of the abdominal wall was possible with
      diagnostic image quality. Abdominal wall pathologies were concurrently diagnosed
      for extended field-of-view sonography with and without utilization of THI. Image
      quality was rated better with THI when compared to extended field-of-view B-Mode
      sonography. In comparison to extended field-of-view B-Mode sonography, the
      agreement between both readers regarding image quality was markedly improved
      using extended field-of-view sonography in combination with THI. With increasing
      thickness of the subcutaneous fat layer, image quality was rated significantly
      better using THI than B-Mode ultrasound. CONCLUSION: Combined use of extended
      field-of-view sonography and THI improves image quality and documentation of
      ultrasound examinations. Especially in obese patients, the use of THI is
      advantageous. Therefore, abdominal wall ultrasound gains additional value in the
      preoperative planning.

PMID- 15573298
TI  - [Hypervascular gastrointestinal stromal tumor of the ileum].

PMID- 15573299
TI  - [Pneumocystis pneumonia -- atypical manifestation in an immunosuppressed patient
      with rheumatoid arthritis].

PMID- 15573300
TI  - [A new MR criterion in the diagnosis of capillary telangiectasis of the brain
      stem].

PMID- 15573301
TI  - Robust multipoint identical-by-descent mapping for affected relative pairs.
AB  - The genetic mapping of complex traits has been challenging and has required new
      statistical methods that are robust to misspecified models. Liang et al. proposed
      a robust multipoint method that can be used to simultaneously estimate, on the
      basis of sib-pair linkage data, both the position of a trait locus on a
      chromosome and its effect on disease status. The advantage of their method is
      that it does not require specification of an underlying genetic model, so
      estimation of the position of a trait locus on a specified chromosome and of its
      standard error is robust to a wide variety of genetic mechanisms. If multiple
      loci influence the trait, the method models the marginal effect of a locus on a
      specified chromosome. The main critical assumption is that there is only one
      trait locus on the chromosome of interest. We extend this method to different
      types of affected relative pairs (ARPs) by two approaches. One approach is to
      estimate the position of a trait locus yet allow unconstrained trait-locus
      effects across different types of ARPs. This robust approach allows for
      differences in sharing alleles identical-by-descent across different types of
      ARPs. Some examples for which an unconstrained model would apply are differences
      due to secular changes in diagnostic methods that can change the frequency of
      phenocopies among different types of relative pairs, environmental factors that
      modify the genetic effect, epistasis, and variation in marker-information
      content. However, this unconstrained model requires a parameter for each type of
      relative pair. To reduce the number of parameters, we propose a second approach
      that models the marginal effect of a susceptibility locus. This constrained model
      is robust for a trait caused by either a single locus or by multiple loci without
      epistasis. To evaluate the adequacy of the constrained model, we developed a
      robust score statistic. These methods are applied to a prostate cancer-linkage
      study, which emphasizes their potential advantages and limitations.

PMID- 15573302
TI  - [Functional outcome at discharge of patients with severe traumatic brain injury
      admitted to a brain damage unit].
AB  - INTRODUCTION: Severe traumatic brain injuries (TBI) are linked to high morbidity
      and mortality rates and have important individual and social costs, not only
      because of the high incidence of deaths they cause but also owing to the large
      number of individuals who are left with some kind of disability. AIMS: The
      purpose of this study was to analyse the epidemiological, clinical, functional
      and rehabilitational aspects of patients with severe TBI admitted to a brain
      damage unit for neurorehabilitation therapy with special emphasis on the
      functional outcome at discharge. PATIENTS AND METHODS: We carried out a
      descriptive study of patients suffering from TBI admitted to the Brain Damage
      Unit of the Institut Guttmann hospital between January 2000 and June 2002. We
      analysed epidemiological (age, sex, cause of the TBI), clinical (aetiology,
      initial Glasgow Coma Scale --GCS--, motor deficit, type of injury, duration of
      post-traumatic amnesia), functional (Glasgow Outcome Scale --GOS--, Level of
      Cognitive Functioning Scale --LCFS-- and Disability Rating Scale --DRS--)
      variables, in addition to patients' destination on discharge. RESULTS: Of a total
      of 174 hospitalised patients, 88.52% were cases of serious TBI, 80% of which
      involved males, with a mean age of 29.72 years (standard deviation: 12.63), and
      an average of 99.28 days' hospitalisation (standard deviation: 60.72). Road
      accidents were the chief cause of the TBI (78%). The most frequent neurological
      injuries were parenchymatous (68.05%), followed by subarachnoid haemorrhages
      (40.58%). 87.58% of the patients presented TBI-related complications. Functional
      improvement at discharge was statistically significant (p < 0.001) as regards the
      GOS, LCFS and DSR scales, and 87.5% of the patients were able to reintegrate into
      their home life. CONCLUSIONS: Despite the severity of the sequelae left by
      serious TBI, the functional outcome at discharge, associated with the high rate
      of reintegration into home life, justifies admission of these patients to a brain
      damage unit for neurorehabilitation therapy.

PMID- 15573303
TI  - [Effects of a physical training program on quantitative neurological indices in
      mild stage type 2 spinocerebelar ataxia patients].
AB  - INTRODUCTION: Type 2 spinocerebelar ataxia (SCA2) is a neurodegenerative disease
      with higher prevalence and incidence in Holguin province, Cuba. At present, there
      is not any drug to counteract the loss of coordinative motor capacities of these
      patients. Thus physical training seems to be the only way to attenuate the course
      of disease. AIMS: To evaluate the effectiveness of a physical training program on
      quantitative neurological indices in SCA2 patients. PATIENTS AND METHODS: A
      samples of 87 SCA2 patients were studied. All subjects underwent a six month
      physical exercise program based on coordination, balance and muscular
      conditioning exercises. Quantitative tests were applied to all patients both
      before and after the application of the exercise program. Comparisons between
      pretest versus posttest values were made to evaluate the improvement in
      neurological indices. RESULTS: All neurological indices both with open eyes and
      closed eyes significantly improved from pretest to posttest. Static balance,
      evaluated by Romberg test, also enhanced with training. CONCLUSIONS: The exercise
      training program significantly improved the neurological indices in SCA2 patient
      with mild stage of disease.

PMID- 15573304
TI  - [Familial multiple sclerosis in Canary Islands].
AB  - INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease that occurs in
      genetically predisposed individuals. Its inheritance is polygenic. Genetic
      epidemiology studies have shown an increased familial aggregation. AIM. To
      determine the prevalence of familial MS (fMS) in a series of patients from the
      Canary Islands. PATIENTS AND METHODS: From a cohort of 266 patients with defined
      MS, during a 6-year period, we investigated prospectively by personal interviews
      the presence of MS on first and second degree relatives. We analysed as well the
      presence of HLA DRB1 in affected families, and also clinical and demographic
      characteristics in fMS and compared them with sporadic MS (sMS). RESULTS: fMS
      prevalence was 13.9% (27 non-related families with 50 affected individuals). The
      HLA DRB01*1501 allele were present in 51,8% of familial cases. We could not found
      either intrafamilial concordance in clinically affected regions and age of onset
      or clinical evolution. We have not found any phenotypic differences between
      familial and sMS. CONCLUSIONS: The prevalence of fMS in our series is comparable
      to that in other Mediterranean populations. Our results do not support that fMS
      was a different clinical entity of sMS and intrafamilial concordance in its
      clinical expression.

PMID- 15573305
TI  - [The development of a scale to evaluate the quality of life in stroke survivors].
AB  - INTRODUCTION: The selection of a measure that can be used to evaluate the outcome
      of therapeutic interventions in stroke patients has had a conceptual problem in
      that there is a need to detect a wide range of deficiencies, disabilities and
      handicaps as part of a patient-based model. It has also suffered from a
      methodological problem due to the lack of systematic attention given to the
      development of standard instruments. AIMS: We conducted this study with the aim
      of getting over these limitations by developing a scale to evaluate the quality
      of life in stroke survivors. SUBJECTS AND METHODS: We followed a methodology that
      had previously been standardised by other authors based on using the opinion
      given by patients and caregivers in the generation of the items to be included.
      This has several stages that include individual interviews with patients,
      caregivers and experts, focal groups with patients and experts, quantitative and
      qualitative analyses of these interviews, two panels of experts to actually draw
      up the instrument, and a pilot test carried out in a sample of 50 patients to
      reduce and group the items. This reducing and grouping process was performed
      taking into account the following: 1. The percentage of responses left
      unanswered; 2. A factorial analysis of the main components; 3. Cronbach's alpha
      coefficient. RESULTS: We interviewed 20 patients and 12 experts; these results
      were later used to classify the above mentioned aspects in order of priority
      according to the frequency with which they appeared in the surveys. Then, we
      elaborated the questionnaire with four areas or subscales by including the
      questions or items in these categories: I. Physical status (17 items); II.
      Emotional status (13 items); III. Activities of daily living (13 items); IV.
      Social and familial functions (13 items). After the pilot study 38 items were
      reorganised into eight domains, according to the factorial analysis: 1. Physical
      problems; 2. Communication; 3. Cognition; 4. Emotions; 5. Feelings; 6. Activities
      of daily living; 7. Familial functions; 8. Social functions. They displayed high
      coefficients of internal consistency. CONCLUSIONS: We developed a new scale for
      evaluating the quality of life for stroke patients and it is now ready to undergo
      its validation process.

PMID- 15573306
TI  - [Cysticercosis as the main cause of partial seizures in children in Peru].
AB  - INTRODUCTION: Seizures are a common neurological problem in the pediatric
      population, and their etiologies in certain developing countries are still not
      clear. From previous studies it is well known that neurocysticercosis is the main
      cause of partial seizures in the adult population in Peru and in many developing
      countries, but the situation has not been clarified for the paediatric population
      yet. PATIENTS AND METHODS: Fifty-four consecutive patients in pre- and school
      ages, with partial seizures, were evaluated in the outpatient clinics and
      emergency room of a public hospital in Lima. Evaluation consisted in clinical
      exam, computed tomography of the head, and in some cases serological evaluation.
      RESULTS: Thirty-seven percent were diagnosed with neurocysticercosis, which was
      found to be the main cause. CONCLUSIONS: The possible explanations may be the
      high incidence of neurocysticercosis in Peru, and the fact that epilepsy and
      seizures are the most common clinical manifestation of neurocysticercosis in
      children. These findings are also representative of the current situation in
      gravel developing countries.

PMID- 15573307
TI  - [Huntington's disease mimicking Tourette syndrome].
AB  - AIM: To report a patient with Huntington's disease, confirmed by a molecular
      genetic study, presenting with clinical features suggesting Tourette's syndrome.
      CASE REPORT: A thirty-years male with personal antecedents of perinatal hypoxia,
      but normal development; and family history (paternal grandfather) of 'abnormal
      repetitive movements of the upper limbs' of adult onset. He had multiple motor
      tics since teenage, and associated vocal tics, bruxism, and compulsions with auto
      and heteroaggresivity. Neurological examination showed motor tics in the
      orolingual area and occasional vocal tics. Neuropsychological examination showed
      a mild impairment of short-term memory and language. Analytical studies including
      blood smears to see acanthocytes and copper metabolism studies were normal, as it
      was a MRI imaging. The molecular genetic study of the patient showed 46 repeats
      of CAG triplets in the exon 1 of the IT-15 genes, while his father (who was
      asymptomatic) showed 40 repeats. It was not possible to study the paternal
      grandfather. CONCLUSIONS: The clinical onset of Huntington's disease mimicking
      Tourette's syndrome is infrequent. This diagnosis should be taken in mind in
      patients with possible Tourette's syndrome and atypical neuropsychiatric
      features.

PMID- 15573308
TI  - [Transient global amnesia following the use of ergots in the treatment of
      migraine].
AB  - INTRODUCTION: Transient global amnesia (TGA) is defined as a selective, or almost
      selective, deficit of the memory that appears suddenly and lasts less than 24
      hours. The aetiopathogenesis of this syndrome remains unknown and different
      theories have been put forward about its epileptic or ischemic origin, or the
      relationship that exists with the neuronal depression that is produced in
      migraine. A number of triggering factors have been described, including the
      taking of distinct pharmaceutical preparations. CASE REPORT: We report the cases
      of two patients with a history of migraines who suffered TGA after taking
      ergotamine and dihydroergotamine, respectively, to treat an attack of migraine.
      CONCLUSIONS: Given the vasoconstriction effect of these drugs, it was concluded
      that in both cases the main factor that triggered the TGA was the ingestion of
      ergots.

PMID- 15573309
TI  - [Atrophy of the cervical spinal cord as a consequence of a prenatal ischemic
      infarct].
AB  - INTRODUCTION: Spinal cord injuries in newborn infants following a traumatic
      delivery are well known, but occasionally cord damage is appreciated in children
      whose birth did not involve any complications; in some of them there has been
      proof of an ischemic process that originated inside the uterus. CASE REPORT: We
      describe the case of a newborn female with atrophy of the cervical spinal cord
      compatible with an intrauterine ischemic infarct. It extended to the C4-C6
      territory of the anterior spinal artery, with greater participation on the left
      side. Clinical symptoms were apparent from the moment of birth and took the form
      of an asymmetric pseudoarthrogryposis in the upper limbs. The left arm was held
      in abduction at the height of the shoulder, with complete flexion of the elbow
      and the hand at the height of the chin was hypotonic, inactive and hypotrophic;
      the right arm was extended and in adduction. The patient presented episodes of
      hyperthermia that remitted on cooling the body. CONCLUSIONS: When faced with a
      newborn infant with symptoms that are compatible with chronic cervical spinal
      cord damage and in the absence of any perinatal traumatic injury, other causes,
      including prenatal ischemic infarct, must be taken into account.

PMID- 15573310
TI  - [Mondini dysplasia: recurrent bacterial meningitis in adolescence].
AB  - INTRODUCTION: Episodes of recurrent bacterial meningitis can occur in patients
      due to either congenital or acquired disorders. Congenital deformity of the bony
      labyrinth can be linked to a fistulous tract communicating it with the
      intracranial subarachnoid space. Mondini deformity is a frequent malformation in
      congenitally deaf patients. CASE REPORT: We report the case of an adolescent with
      a history of being unable to hear in one ear who, from the age of 10 years, began
      to suffer repeated bacterial meningoencephalitis with microbiological recovery of
      Streptococcus pneumoniae on three occasions. The type of germ recovered in the
      cerebrospinal fluid (CSF) and the history of congenital deafness that was
      detected when the patient was 3 years old were the diagnostic clues to the
      possible anomaly of the inner ear with a CSF fistula. The clinically proven CSF
      rhinorrhea contributed to the diagnosis of an ear anomaly with a fistula.
      Computerised axial tomography and magnetic resonance studies of the petrous
      portion of the temporal bone revealed the malformation that was later found and
      closed during the surgical intervention on the affected ear. The clinical absence
      of rhinorrhea, a year's progression without new infections after operating on the
      patient and post-surgery imaging studies were all proof that the fistula had
      closed. CONCLUSIONS: Mondini dysplasia with CSF fistula must be included as a
      possible diagnosis when faced with a patient with recurrent bacterial
      meningoencephalitis. Imaging studies, especially magnetic resonance, enable the
      clinician to check the diagnosis and the CSF fistula can be closed with ear
      surgery.

PMID- 15573311
TI  - [In utero macrocephaly as clinical manifestation of glutaric aciduria type I.
      Report of a novel mutation].
AB  - INTRODUCTION: Macrocephaly is a pivotal clinical sign, associated with multiple
      neurological diseases, particularly neurometabolical ones, such as the glutaric
      aciduria type I (GA I). This aciduria resulting from the genetical deficiency of
      the enzyme glutaryl-CoA dehydrogenase (GCDH). Is a relatively common cause of
      acute metabolic brain damage in early childhood. We report on one case of GA I,
      with early manifestations since fetal period and a novel mutation. CASE REPORT:
      Our patient was referred due macrocephaly in utero and occipitofrontal head
      circumference above the 98 percentile for chronologic age during first few months
      of life, hypotonia and development delay. The metabolic investigations of organic
      acids in urine and acylcarnitine profile in blood, the brain magnetic resonance
      and the molecular analyses of the glutaryl-CoA deshidrogenase gene, confirm the
      diagnosis. The molecular analysis allowed to identify one previously described
      mutation A293T and a novel mutation IVS5-2 A>G. CONCLUSION: It is important the
      recognition of in utero macrocephaly as a sign to early diagnosis of glutaric
      aciduria type I to initiate specific therapy to prevent the encephalopathic
      crises and minimize brain damage in patients who are already neurologically
      impaired.

PMID- 15573312
TI  - [Moya-moya syndrome and arterial dysplasia associated to Down syndrome].
AB  - INTRODUCTION: Ischemic vascular pathologies are predominant among the
      neurological processes associated to Down syndrome. Thrombosis of the venous
      sinuses, Moya-moya syndrome and arterial dysplasia, among others, stand out for
      their association with this syndrome. CASE REPORT: We describe the case of a 19
      year-old female patient suffering from Down syndrome who visited because of
      deficiency symptoms of an ischemic origin; diagnosis was based on angiographic
      disorders compatible with Moya-moya syndrome in the left carotid tree and
      arterial dysplasia in the right carotid tree. Data concerning the medical
      history, physical examination, complementary tests, treatment applied and
      evaluation of the patient's clinical progress are reported. At the same time, the
      patient was also diagnosed as suffering from Graves-Basedow disease, which is
      contemplated in the aetiological study carried out on these and other vascular
      anomalies and which have often been described in relation to Down syndrome.
      CONCLUSIONS: The particular interest of our case lies in the fact that the two
      pathological processes occur in the same patient, although only one of them was
      symptomatic. Both of these vascular anomalies have been described in association
      with Down syndrome separately, but the simultaneous presence of both of them in
      the same patient is infrequent. We suggest the possibility of a common
      aetiological link between the two processes, which in turn accounts for their
      association with Down syndrome.

PMID- 15573313
TI  - [Function and dysfunction of the startle reaction in humans].
AB  - INTRODUCTION AND DEVELOPMENT: The startle reaction is one of the fastest
      movements of human beings in response to a sensory stimulus. It is likely that
      the central nervous system uses the circuits of the SR for the execution of a
      ballistic movement. Evidence in favour of the participation of the startle
      reaction circuits in the execution of a ballistic movement has been gathered by
      combining the presentation of startle reaction-inducing stimuli with the
      imperative signal in a reaction time task experiment. In this situation, in which
      subjects are highly prepared for movement execution, the reaction becomes
      accelerated but the movement pattern is not modified. On top of that,
      acceleration is limited to the movement per se, and it does not involve the
      subjective perception of the movement. Impairment of the central control of the
      startle reaction may lead to excess or reduction of the response. One of the
      examples of excessive response is hyperekplexia, in which patients cannot avoid
      having a startle reaction to unexpected stimuli. Reduced startle reaction occurs
      in parkinsonism and, specially, in progressive supranuclear palsy. CONCLUSIONS:
      One of the best known mechanisms of control of the startle reaction is prepulse
      inhibition. This phenomenon is likely the consequence of sensory signal
      processing at the brainstem level. The role of the prepulse inhibition is to
      avoid disruption of the sensory processing by the interference of another input.
      Prepulse inhibition is abnormally reduced in patients with parkinsonism, as an
      expression of the abnormal control of brainstem circuits by the basal ganglia. It
      has been also found abnormal in patients with Huntington's disease and in some
      patients with dystonia.

PMID- 15573314
TI  - [Pathogenetic mechanisms in phenylketonuria: disorders affecting the metabolism
      of neurotransmitters and the antioxidant system].
AB  - AIM: To review the clinical and biochemical changes in neurotransmission and
      antioxidant system in phenylketonuric patients under dietary treatment.
      DEVELOPMENT: Phenylketonuria (PKU) is an inborn error of metabolism caused by
      decreased activity of the enzyme L-phenylalanine-4-mono-oxigenase that
      synthesizes tyrosine from phenylalanine. According to analytical data from PKU
      patients and to experimental studies in animal models, high phenylalanine values
      in plasma and tissues seem to be related with defective biosynthesis of
      neurotransmitter (mainly serotonin and dopamine) and impairment of antioxidant
      system. Despite dietary treatment, PKU patients usually present moderate
      hyperphenylalaninemia over the evolution of the disease that might cause clinical
      and biochemical abnormalities. CONCLUSIONS: Increased plasma phenylalanine
      concentrations and dietary treatment might be related with neurotransmitter and
      antioxidant system abnormalities in human phenylketonuria. These biochemical
      alterations might be involved in the physiopathology of PKU.

PMID- 15573315
TI  - [The chronopathology of prion encephalopathies].
AB  - INTRODUCTION: Prion encephalopathies are a group of diseases with a hereditary or
      acquired origin which, after a long asymptomatic period, give rise to rapidly
      progressing neurological disorders. This progression can only be explained by an
      exponential growth of the pathogenic protein load, which allows to keep the load
      in low levels for many years and then to grow swiftly in a few months.
      DEVELOPMENT: Bearing in mind the knowledge currently available about the
      pathogenesis of prion diseases and patients' clinical progression, it becomes
      possible to distinguish several different periods of progression, the length of
      which can be estimated for each disease by reviewing the series of cases
      published to date. In general, the infectious prion diseases have a shorter
      period of latency than the hereditary ones and those caused by insertion of
      genetic material are associated to shorter latencies and to longer periods of
      illness than those caused by sporadic mutations. CONCLUSIONS: The rate of growth
      of the prion load depends essentially on how fast the pathogenic prion protein
      replicates; nevertheless, this growth is also modulated by other factors, many of
      which are polymorphisms in certain positions on the gene coding for prion protein
      or in other genes.

PMID- 15573316
TI  - [Clinical techniques for use in neurological physical examinations. III. Sensory
      functions].
AB  - AIMS: The purpose of this work is to focus on the main practical aspects of the
      techniques used for the neurological physical examination of the sensory
      functions and to present an approach for the practice of this study. DEVELOPMENT:
      Despite the difficulty often involved in interpreting its results, today the
      formal examination of sensation is still an important part of a complete
      neurological evaluation and remains valid in the search for a correct diagnosis
      and suitable treatment. We recommend clinicians to carry out a brief but
      consistent and effective exploration in a systematic, flexible and orderly manner
      to check for abnormalities in the sensory functions. Should any anomalies be
      detected, then a more detailed and thorough neurological exploration must be
      performed selectively. We present a detailed review of the practical aspects of
      the main techniques used in the physical examination of this neurological
      category. In addition to the tests used to examine the peripheral and cortical
      sensory systems, we also describe other techniques designed to trigger pain or
      other sensory symptoms due to radicular lesions or injury to the median nerve.
      CONCLUSIONS: We present a detailed description of the main clinical techniques
      used in the neurological physical examination of the sensory functions, as well
      as an approach that allows them to be performed on adult patients. In addition,
      we underline the importance of physically examining the sensory functions in
      contemporary medicine and the need to continually perfect the way these
      techniques are performed in order to achieve an efficient clinical practice.

PMID- 15573317
TI  - [Electrical stimulation of the vagal nerve: from experimental to clinical
      aspects].
AB  - INTRODUCTION AND AIMS: This review focuses its attention on the studies that have
      been conducted to determine the influence of electrical stimulation of the vagal
      nerve on experimentally induced convulsive activity and its application in the
      clinical field. The literature published to date describes an anticonvulsive
      effect on the seizures triggered by pharmacological agents and by electrical
      stimulation such as electroshock, and in the amygdaline electrical kindling model
      a delay in the generalisation of the convulsive activity is observed.
      DEVELOPMENT: The first experimental observations showed that electrical
      stimulation of the vagal nerve can have effects on EEG activity, including
      synchronisation and desynchronisation of the electrical activity of the brain, as
      well as promoting an increase in the amount of REM sleep. These observations
      served as the basis for the renewed interest in the electrical stimulation of the
      vagal nerve in experimental models and testing its effectiveness in patients with
      medication-resistant epilepsy. Nevertheless, the mechanisms accounting for the
      anticonvulsive effect remain unknown. CONCLUSIONS: These observations open up the
      possibility of studying the role played by neurotransmitters and neuromodulators
      in the anticonvulsive process of the electrical stimulation of the vagal nerve in
      experimental models of epilepsy and offer evidence of its possible action in the
      human brain.

PMID- 15573318
TI  - [Neurochemical treatment of Parkinson's disease and essential tremor].
AB  - INTRODUCTION: Recent technological advances along with new neuroimaging
      techniques and progress in neuro-monitoring have provided us with new
      therapeutical options from the neurosurgical point of view in the management of
      movement disorders. Deep brain stimulators become more and more frequently used
      in the last few years since they have reversible effects, are easily implantable
      and have shown good initial results. However, only now we start knowing the
      clinical effects in the middle run. AIM: To review the main neurosurgical options
      in Parkinson's disease and tremor. DEVELOPMENT: We reviewed the articles
      considering ablative or stimulating neurosurgical treatments in these diseases,
      and we grouped the results according to the technique performed and the time of
      follow-up. CONCLUSION: Clinical results are often similar despite the use of
      different techniques. However, the side-effects are critical in deciding which
      technique should be used once medical therapy has been considered insufficient.

PMID- 15573319
TI  - [Cystic acoustic neuroma].

PMID- 15573321
TI  - [Actinomyotic brain abscess].

PMID- 15573322
TI  - [Neuroepidemiological map of Caldas, Colombia (1997-1999)].

PMID- 15573323
TI  - [Creutzfeldt-Jakob disease with rapidly progressive presentation].

PMID- 15573324
TI  - [Mononeuropathy of the anterior interosseous nerve related to a first generalised
      tonic-clonic seizure].

PMID- 15573325
TI  - [Motor neuron syndrome associated to the HTLV-1 retrovirus].

PMID- 15573327
TI  - [Regarding the term 'denervation'].

PMID- 15573326
TI  - [Myoclonias triggered by diclofenac].

PMID- 15573330
TI  - The prevalence and nature of errors and near errors reported by hospital staff
      nurses.
AB  - The purpose of this article is to describe the nature and prevalence of errors
      and near errors reported by 393 full-time hospital staff nurses. One hundred
      nineteen nurses (30%) reported making at least one error, and 127 nurses (33%)
      reported at least one near error, for a total of 199 errors and 213 near errors
      in the 28-day data collection period. Although the majority of errors and near
      errors identified in this study involved medication administration, the number of
      procedural, transcription, and charting errors that occurred suggests the need
      for further examination of the way we currently deliver health care.

PMID- 15573331
TI  - Nurses' adoption of technology: application of Rogers' innovation-diffusion
      model.
AB  - This qualitative study applied Everett Rogers' innovation-diffusion model to
      analyze nurses' perceptions toward using a computerized care plan system. Twelve
      nurses from three respiratory intensive care units in Taiwan voluntarily
      participated in a one-on-one, in-depth interview. Data were analyzed by constant
      comparative analysis. The content that emerged was compared with the model's five
      innovation characteristics (relative advantage, compatibility, complexity,
      trialability, and observability), as perceived by new users. Results indicate
      that Rogers' model can accurately describe nurses' behavior during the process of
      adopting workplace innovations. Related issues that emerged deserve further
      attention to help nurses make the best use of technology.

PMID- 15573332
TI  - Implementing evidence-based practice: walking the talk.
AB  - Russworm and Larrabee's (1999) six-step model for evidence-based practice (EBP)
      was used by 10 nursing teams to seek answers to clinical questions. These teams,
      primarily composed of staff nurses, participated in a health region-wide EBP
      program over 1 year. Overall, the model served as a useful mechanism for
      examining practice-derived questions. However, additional strategies needed to be
      incorporated by the project teams. These included making decisions about
      change/no change at an earlier stage than was suggested by the model; seeking
      additional evidence including survey data to benchmark "best" practices; and
      ensuring colleagues' and managers' input, support, and involvement. Four project
      teams (three of which addressed nursing procedural questions) found insufficient
      empirical evidence on which to base change; the outlook for directing evidence
      based practice was promising for the remaining six projects. The EBP program was
      judged to be highly satisfactory to participants and their managers.

PMID- 15573333
TI  - The effects of nursing interventions to enhance mental health and quality of life
      among individuals with heart failure.
AB  - Heart failure (HF) is a progressive, debilitating syndrome with significant
      physical and psychological comorbidities. As psychosocial variables have been
      found to contribute to HF morbidity and mortality, methods to improve mental
      health and quality of life have been explored. This study examined the effects of
      mutual goal setting and supportive-educative nursing interventions on mental
      health and quality of life. An experimental, repeated-measures design with a
      convenience sample of 88 participants was used. The mutual goal setting nursing
      intervention was found to significantly support improved mental health and
      quality of life in this population over a 6-month period.

PMID- 15573334
TI  - Nurses' facilitators and barriers for taking a sexual history in Taiwan.
AB  - The purpose of this study was to explore factors that Taiwanese nurses perceive
      as facilitators or barriers for taking a sexual history. These nurses (N = 391)
      perceived the two major facilitators to be the desire of a nurse to know whether
      or not a patient's sexual history was related to his/her illness and when a
      patient specifically mentioned a sexual problem. The major two perceived barriers
      were patients feeling either embarrassed about the issues of sexuality or that
      their sexuality was unrelated to their treatment and a lack of professionals for
      referral of patients for further consultations. Enhancing Taiwanese nurses'
      perceived facilitators and decreasing their perceived barriers to sexual history
      taking should be an essential goal for nursing.

PMID- 15573335
TI  - Safety and effectiveness of large-volume enema solutions.
AB  - The effectiveness and side effects of three types of enema solutions were
      compared in healthy subjects. Using a repeated-measures, double-blind design, the
      three different enemas (soapsuds, tap water, and polyethylene glycol-electrolyte
      solution) were given at 1-week intervals to 24 healthy volunteers. Soapsuds and
      tap water enemas produced significantly greater returns than polyethylene glycol
      electrolyte solution (PEG-ES) and were also more uncomfortable. Rectal biopsies
      showed surface epithelium loss after soapsuds and tap water but not after PEG-ES
      enemas. Before recommending changes in nursing practice, further research is
      needed to determine the mechanism for the surface epithelium damage and to
      determine if this damage produces a stronger defecation stimulus and discomfort.

PMID- 15573336
TI  - Intradermal injections: traditional bevel up versus bevel down.
AB  - This study used qualitative and quantitative methods to examine differences
      regarding correct placement of injectate, leaking or bleeding, time to administer
      injection, and comfort of person administering, and receiving an intradermal
      injection. Each (N = 98) administered and received two injections. Subjects
      evaluated their comfort on a Likert scale. After second injection, each reported
      which was better. Most of the time (82%), a wheal was produced. Leaking or
      bleeding occurred a fourth of the time. Subjects rated the first injection better
      (p < 0.05) with no preference regarding technique. Subjects administering
      injections reported bevel up more comfortable (p < 0.01). Bevel up was
      significantly faster.

PMID- 15573337
TI  - Using PDAs for data collection.
AB  - Advances in handheld computer technology are making data collection faster,
      easier, and more accurate. In this article, the use of personal digital
      assistants (PDAs) to collect data for a study on elder neglect is described and
      evaluated. Methods for integrating this technology into a research study are
      discussed as are suggestions for increasing the performance of data collectors
      using these devices. The authors offer some practical solutions for researchers
      and clinicians planning to use PDAs in their research.

PMID- 15573338
TI  - Weight change, body image, and quality of life in HIV disease: a pilot study.
AB  - Fat distribution alterations and lipodystrophy occur as part of a broad spectrum
      of body alterations in human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS). Recent advances in HIV therapies, including
      highly active antiretroviral therapy, contribute to these fat distribution
      alterations. The purpose of this pilot study was to investigate the relationships
      of weight change, body image, length of time with HIV/AIDS diagnosis, and quality
      of life in HIV disease. The sample consisted of 23 men with mean age of 42.2
      years (SD = 8.2) and 17 women with mean age of 36.8 years (SD = 5.2).
      Participants reported a net increase in weight from 3 months prior (M = 2.4 lb,
      SD = 12.9 lb) and 12 months prior (M = 10.9 lb, SD = 19.1 lb). They also reported
      that their weight was greater than their ideal weight (M = 9.2 lb, SD = 22.9 lb).
      Body image scores (0-100 scale) were found to be significantly (F((1, 37)) =
      5.41, p = .03) higher for women (73.1 +/- 17.0) compared with men (60.2 +/-
      17.0). Although HIV-positive participants had slightly higher body image scores
      (M = 68.0, SD = 17.0) compared with participants with AIDS (M = 60.5, SD = 18.8),
      there was no significant difference (F((1, 37)) = 1.56, p = .22) in body image
      scores between those with HIV and those with AIDS. Finally, weight change was
      related to three scales of the Medical Outcomes Study-HIV: mental health (r =
      .42, p = .03), vitality (r = .53, p = .006), and quality of life (r = .45, p =
      .02) for men. There were no significant correlations between weight change and
      quality of life domains for women. Education of clinicians and individuals living
      with HIV/AIDS should focus on the assessment, management, and evaluation of
      weight change during the course of HIV disease.

PMID- 15573339
TI  - Safety and efficacy of the POP technique for restoring patency to occluded PIC
      catheters.
AB  - Peripheral-inserted central catheters (PICCs) offer a successful alternative to
      peripheral venipuncture for long term medication therapy. When catheters become
      occluded, the nurse must intervene to avoid delayed or missed treatments.
      Pharmacological interventions are costly and not without risks. The purpose of
      this exploratory study was to test a mechanical percussive POP technique to
      restore patency. Thirty PICC catheters were clotted with human blood and
      incubated for 8 hours in a 35 degrees saline bath. Using the percussive POP
      technique, a 10-mL syringe with 1 mL of saline restored patency in 86% of the
      occluded catheters. The safety and effectiveness of the POP technique in vitro
      was established.

PMID- 15573340
TI  - District nursing in Australia.

PMID- 15573341
TI  - Some tips on getting funding for health services research.

PMID- 15573342
TI  - Coronectomy: a time to ponder or a time to act?

PMID- 15573343
TI  - Coronectomy: a technique to protect the inferior alveolar nerve.
AB  - PURPOSE: Damage to the inferior alveolar nerve when extracting lower third molars
      is often caused by the intimate relationship between the nerve and the roots of
      the teeth. The technique of coronectomy, or intentional root retention, may
      minimize this problem. PATIENTS AND METHODS: Forty-one patients underwent
      coronectomy on 50 lower third molars with follow-up of at least 6 months. The
      technique of coronectomy deliberately protected the lingual nerve as part of the
      surgical procedure. All roots were left at least 3 mm below the buccal and
      lingual plates of bone. All patients were radiographed preoperatively,
      immediately postoperatively, and after 6 months. RESULTS: There were no cases of
      inferior alveolar nerve-involved damage in this study of 41 patients who
      underwent 50 coronectomies. There was 1 case of transient lingual nerve
      involvement, probably from the use of the lingual retractor. One patient required
      subsequent removal of the roots of both lower third molars because of failure to
      heal, and 1 patient required subsequent removal of a root because of subsequent
      migration to the surface. Root migration was noted in approximately 30% of
      patients over a 6 month period. CONCLUSION: Coronectomy appears to be a viable
      technique in those cases where removal of the whole tooth might put the inferior
      alveolar nerve at considerable risk of damage. The technique appears to be
      associated with a low incidence of complications, but subsequent migration of the
      roots may be an issue in the long term.

PMID- 15573344
TI  - Lower-half facial migraine: a report of 11 cases.
AB  - PURPOSE: Vascular pain of the face constitutes a variant of pain of the head, and
      includes migraine, cluster headache, paroxysmal hemicrania, and a facial variant
      of the so-called lower-half migraine. Lower-half facial migraine is a condition
      difficult to classify; according to the international classifications it could
      not be found as an individual entity. The objective of the present study is to
      determine the difficulties we encountered in diagnosis, the ineffective
      treatments provided, and the pharmacologic treatment effect. PATIENTS AND
      METHODS: A study is made of 11 cases of lower-half facial migraine, corresponding
      to 10 women and 1 man (mean age, 35 years), commenting on the clinical
      characteristics of the disorder and its treatment options. The location of the
      pain often mimics dental pain, and can lead to a mistaken diagnosis and to the
      application of inappropriate therapeutic measures. Forty-five percent of the
      patients had a history of endodontic treatment before the development of pain in
      the initially affected quadrant. Once the pain had developed, extractions were
      carried out in 36% of cases in an unsuccessful attempt to secure symptom relief.
      Our pharmacologic treatment consisted of ergotamine in 9 cases and the remaining
      2 patients received indomethacin. RESULTS: Nine patients (82%) improved as a
      result of treatment, with an important reduction in the frequency of the pain
      episodes and intensity of pain. One patient failed to respond to ergotamine,
      while another patient failed to improve with indomethacin. Both were prescribed
      only minor analgesics. CONCLUSION: The treatment of migraine occurring in the
      face is no different than that provided for pain occurring in the head.

PMID- 15573345
TI  - Reconstruction of skin cancer defects of the auricle.
AB  - PURPOSE: This article reviews the results of reconstruction of surface defects of
      the auricle after removal of skin cancer, and discusses the results of the
      delayed reconstruction method of care and modalities of treatment. PATIENTS AND
      METHODS: Fifty-four patients with 62 defects involving various locations on the
      auricle were treated. Management included direct closure, secondary
      epithelization, full thickness skin grafts, local flaps using direct advancement,
      and rotational advancement flaps using one or more stages. RESULTS: Nine defects
      were treated by direct closure with adjacent tissue, 12 defects healed by
      secondary epithelization, and 13 patients were treated with a full thickness skin
      graft. Twenty-eight defects were reconstructed with local flaps, which included
      the direct advancement, rotational flaps, transposition, and subcutaneous island
      flaps. No infections occurred. CONCLUSION: Many options are available for
      reconstruction of auricular defects which yield acceptable results. Factors to
      consider before choosing a reconstructive format include size, location, and
      depth of the defect, patient medical history, smoking, and esthetic concerns.
      This review exposed that patients easily accept the "delayed" method of
      reconstruction. Delaying allows the surgeon time to research options for care and
      allows the patient choices of secondary epithelization and significantly reduced
      costs of care.

PMID- 15573346
TI  - On neurosensory disturbance after sagittal split osteotomy.
AB  - PURPOSE: The purpose of this retrospective study was to assess the incidence of
      the neurosensory disturbance (NSD) after sagittal split osteotomy and evaluate
      NSD in relation to patient age, gender, satisfaction, and effect of steroids.
      PATIENTS AND METHODS: Questionnaires were mailed to all patients (31 women, 19
      men) who underwent bilateral sagittal split osteotomy between 1995 and 1999, at
      least 1 year after the operation. Patients were queried about perceived NSD in
      the distribution of both inferior alveolar and lingual nerves, duration of these
      changes, and any influence of these changes on their quality of life. RESULTS:
      Eighty-six percent of the mailed questionnaires were returned and analyzed (27
      women, 16 men). Eight patients with 10 affected sides (11.6% of sides) reported
      long lasting NSD corresponding to the distribution of the inferior alveolar
      nerve. NSD was reported in 16.7% of the operated sides in women, while 3% of the
      operated sides in the men had such changes. Fifty percent of the operated sides
      in patients over 40 years of age were affected. Steroid treatment seemed to
      decrease NSD. Four patients (9%) were not satisfied, but only 1 attributed the
      dissatisfaction to sensory impairment. CONCLUSION: The incidence of NSD after
      sagittal split osteotomy increases in patients over the age of 40. Steroid
      regimen might be beneficial in reducing NSD after sagittal split osteotomy,
      although further investigation is required. The discomfort of the nerve damage
      seems outweighed by the result of function and esthetics.

PMID- 15573347
TI  - Passive repositioning of maxillary fractures: an occasional impossibility without
      osteotomy.
AB  - PURPOSE: To present cases where passive repositioning of maxillary fractures was
      not achievable during surgery, and a method to provide passive occlusal
      positioning in those cases. PATIENTS AND METHODS: Over a 10-year period, the
      maxillae of 24 patients with fractures of the maxilla could not be passively
      repositioned during surgery. In these cases, a Le Fort I osteotomy was performed
      in addition to reduction and fixation of the other midfacial fractures. RESULTS:
      All patients had passive restoration of their pretrauma occlusion during surgery.
      All patients except 1 had maintenance of their pretrauma occlusion at the last
      follow-up visit (6 weeks or more) following surgery. CONCLUSION: When passive
      positioning of the maxilla is not possible, a concomitant Le Fort I osteotomy can
      provide passive positioning of the occlusion.

PMID- 15573348
TI  - Skeletal relapse after mandibular advancement and setback in single-jaw surgery.
AB  - PURPOSE: The aim of this study was to identify contributing factors to skeletal
      relapse by analyzing cephalometric changes after bilateral sagittal split ramus
      osteotomy. PATIENTS AND METHODS: This study included 60 consecutive patients who
      underwent either mandibular advancement (30 patients) or setback surgery (30
      patients). There were 36 women and 24 men (mean age, 23 years). The radiographs
      of these patients taken immediately before operation, at 1 week, and 14 months
      postoperatively were studied. To analyze the influence of hyper- and
      hypodivergent facial patterns on the surgical outcome, the patients were divided
      into 3 groups according to the mandibulo-nasal plane angle. The position of the
      maxilla was also taken into account. RESULTS: Measured at B-point, skeletal
      relapse was 1.3 mm (30%) after mean advancement of 4.4 mm and 0.8 mm (12%) after
      setback of 6.0 mm. The magnitude of the surgical movement correlated with
      skeletal relapse. However, the correlation was not linear. Advancement of greater
      than 7 mm is associated with an increased tendency to relapse (r=0.52), but
      setback of more than 12 mm with a decreased tendency (r=-0.95). The retrognathic
      patients with a high mandibulo-nasal plane angle (hyperdivergence) had 30% higher
      relapse rate. Patients with hypodivergent facial patterns had less relapse in
      both advancement and setback surgery. CONCLUSION: Skeletal relapse was affected
      by magnitude of surgical movement and different facial patterns according to the
      mandibulo-nasal plane angle; however, influences of both factors were different
      between mandibular advancement and setback.

PMID- 15573349
TI  - Multimodal image registration for localization of sentinel nodes in head and neck
      squamous cell carcinoma.
AB  - PURPOSE: The aim of this clinical study was to propose a new method of
      preoperative 3-dimensional localization of the neck sentinel node in clinically
      and radiographically N0 squamous cell carcinoma of the oral cavity. PATIENTS AND
      METHODS: This prospective study was carried out between August 2002 and August
      2003. Ten patients with staged oral squamous cell cancer underwent this method of
      preoperative localization of the sentinel lymph node. At the present time,
      lymphoscintigraphy is recognized as the investigation of choice for the
      preoperative detection of sentinel nodes. Although we found it to be highly
      sensitive (100% in our study), it does not allow precise localization of the
      sentinel node in the anatomic context of the neck. To overcome this drawback, we
      used multimodal image registration applied to the cervical region in association
      with the imaging modalities of scintigraphy (single-photon emission computed
      tomography [SPECT] and gamma transmission) and computed tomography (CT). SPECT
      and gamma transmission (barium-133 sources) were carried out with a triple-head
      Philips-Marconi camera (Philips Medical System, Cleveland, OH), and CT was
      carried out with a General Electric console (GE Medical Systems, Milwaukee, WI).
      Gamma transmission was used to place the SPECT images in a reference cervical
      anatomic context (CT images). Registration involved the use of a manual method
      based on definition of homologous volume structures. RESULTS: Preoperative image
      registration effectively localized the cervical sentinel node in 9 of the 10
      patients, enabling a guided surgical approach in 90% of cases. The sentinel node
      was localized and resected using a hand-held gamma probe. CONCLUSIONS: This
      original study adapts a new tool (multimodal image registration) to obtain
      precise preoperative localization of the cervical sentinel node in N0 oral
      squamous cell carcinoma. We confirmed the feasibility of this method in this
      indication. Although this method is a novel one, we believe that it will become
      extremely useful once a consensus has been reached on exclusive excision of the
      cervical sentinel node in oral cancers, as is the case for melanoma or breast
      cancer.

PMID- 15573350
TI  - Predictability of soft tissue profile changes following bimaxillary surgery in
      skeletal class III Chinese patients.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of soft tissue
      profile predictions generated by a recently developed computer program (Computer
      Assisted Simulation System for Orthognathic Surgery [CASSOS] 2001, SoftEnable
      Technology, Ltd, Hong Kong) in Chinese skeletal Class III patients treated with
      bimaxillary surgery. MATERIALS AND METHODS: Presurgical and posttreatment lateral
      cephalograms of 35 Chinese patients who had combined 1-piece Le Fort I and
      bilateral sagittal split osteotomies were digitized using the CASSOS 2001
      program, and a cranial base superimposition was performed. The hard tissue
      movements were simulated on the presurgical cephalogram until good
      superimposition of the hard tissues on the presurgical and posttreatment
      cephalograms was achieved. A customized cephalometric analysis consisting of 32
      linear measurements was used to analyze the differences in the soft tissue
      profile between the actual posttreatment results and the computer-generated
      predictions. RESULTS: Comparison of the predicted and actual changes found that
      16 of the 32 soft tissue measurements were significantly different ( P <.05).
      Most of the significant prediction errors were observed in the upper and lower
      lip region. The software tended to underestimate the vertical position of both
      the upper and lower lip and overestimate the horizontal position of the lower
      lip. However, the mean differences were relatively small, with the greatest mean
      difference being 2 mm in the vertical position of stomium inferius. The CASSOS
      2001 program produced a clinically useful prediction of soft tissue profile
      changes following bimaxillary surgery in skeletal Class III Chinese patients.

PMID- 15573351
TI  - Cartilage formation by serial passaged cultured chondrocytes in a new scaffold:
      hybrid 75:25 poly(L-lactide-epsilon-caprolactone) sponge.
AB  - PURPOSE: This study was designed to determine whether multipled chondrocytes
      immersed in a new scaffold, 75:25 poly(L-lactide-epsilon-caprolactone) sponge
      coated with type I collagen (75-PLC scaffold), could be used to generate
      cartilage tissue in vivo and to evaluate the correlation between cartilage
      generation and the phenotype of the proliferated chondrocytes. MATERIALS AND
      METHODS: Rat chondrocytes were suspended in 75-PLC scaffold at a density of 1 x
      10 7 cells/mL after proliferation in a monolayer for 1 (P1) to 4 passages (P4)
      and implanted in nude mice for 4 weeks. Cells were characterized by the
      expression of genes encoding type II collagen, aggrecan, and type I collagen by
      Northern hybridization, and consequently, the newly formed tissue was evaluated
      histologically. RESULTS: The expression of aggrecan messenger RNA gradually
      decreased with the passaged cultures; however, the expression of type I collagen
      messenger RNA increased with time. The cartilage formations in all specimens were
      found not only in P1 chondrocytes but also in P2 chondrocytes, although when P3
      chondrocytes were grafted, approximately 50% of cartilage formation was still
      observed up to but not beyond P4. CONCLUSION: It is suggested that cartilage
      tissue is generated with cultured chondrocytes up to P2 but not beyond P4.
      Northern blot analysis is useful for the assessment of whether the cells are
      capable of regeneration.

PMID- 15573352
TI  - Prototype testing for a new bioabsorbable Le Fort III distraction device: a pilot
      study.
AB  - PURPOSE: The goal of the study was to design and test prototypes for a new,
      internal resorbable Le Fort III distractor in the minipig model. MATERIALS AND
      METHODS: Le Fort III osteotomies were performed on 3 juvenile minipigs, followed
      by implantation of the bioabsorbable distractors. After a 5-day latency period,
      the distraction progressed at a rate of 1 mm/day in 2 equal increments for 12
      days. This was followed by a 6-week consolidation phase. Cephalometric
      radiographs were taken postoperatively, on completion of distraction and after
      the consolidation phase, to evaluate the amount of distraction that was obtained.
      Necropsy was performed at the completion of each experiment. RESULTS: The first
      minipig was sacrificed at the end of the distraction period because of device
      failure. On necropsy, it was noted that the anterior footplate on either side had
      failed. The second minipig was sacrificed during the latency period because of
      severe pneumonia. On necropsy, it was noted that none of the footplates had
      failed but that the distraction barrels on either side had become dislodged from
      the anterior bioabsorbable footplates. The third minipig was sacrificed at the
      end of the distraction period because of device failure. On necropsy, it was
      noted that the posterior bioabsorbable footplates on either side were fractured
      across the posterior screw lines. CONCLUSIONS: The bioabsorbable devices
      evaluated in this study could not withstand the forces generated during
      distraction osteogenesis in the minipig model. Experience with the prototypes may
      help in designing internal bioresorbable Le Fort III distraction devices.

PMID- 15573353
TI  - Facial nerve repair with epineural suture and anastomosis using fibrin adhesive:
      an experimental study in the rabbit.
AB  - PURPOSE: An experimental model in rabbits was used to compare epineural suturing
      and fibrin adhesive anastomosis for facial nerve repair. MATERIALS AND METHODS:
      Thirty-four facial nerves from 17 rabbits were isolated, transected, and
      anastomosed, with an evaluation of their electrophysiologic and histologic
      parameters. The rabbits were divided into 2 groups of 5 and 12 animals,
      respectively: a 10-mm defect was made in the right facial nerve in the first
      group, with transection and epineural suturing of the left nerve, followed by
      death after 120 days. This was the control-versus-epineural suture group. In the
      second group, the right facial nerve was transected and subjected to epineural
      suturing, while the left nerve was transected and anastomosed using fibrin
      adhesive. The rabbits were killed 15, 30, 60, and 120 days after the
      microsurgical procedure. This was the epineural suture-versus-fibrin adhesive
      group. RESULTS: From day 30, the number of regenerated axons increased with time
      in the epineural suture and fibrin adhesive anastomotic specimens. Epineural
      suture showed more regenerated axons and a faster linear rate of regeneration
      than anastomosis with fibrin adhesive. The reduction in conduction velocity
      decreased significantly with time with the same linear pattern for both suture
      techniques. CONCLUSIONS: Epineural suturing offered superior performance versus
      anastomosis with fibrin adhesive in terms of axon count but not in decrease in
      conduction velocity.

PMID- 15573354
TI  - Horizontal alveolar distraction of the narrow maxillary ridge for implant
      placement.
AB  - PURPOSE: The purpose of this report was to describe a surgical technique for
      performing horizontal alveolar distraction of the knife-edge maxillary ridge.
      PATIENT AND METHODS: The patient was a 17-year-old woman with atrophy of the
      alveolar rim in the anterior upper jaw, which had inadequate width for implant
      placement. The transport segment was constructed by the osteotomy of the labial
      cortex of the alveolus. A transport plate of a distractor (LEAD system; Stryker
      Leibinger, Kalamazoo, MI) was placed on the transport segment. The distraction
      rod was inserted horizontally, and put in contact with the palatal cortex at the
      top. A base plate was not placed. RESULTS: The alveolar distraction was
      successfully performed to gain 6.0 mm in width and 0.5 mm in height, allowing
      placement of three 14-mm implants. All the implants were integrated so as to
      support the prosthesis. CONCLUSIONS: Alveolar distraction can be useful for
      augmenting the narrow ridge horizontally and placement of implants.

PMID- 15573355
TI  - Maxillary sinus and ridge augmentations using a surface-derived autogenous bone
      graft.
AB  - PURPOSE: The purpose of this article is to describe a new technique and the
      anatomic sites for cutting and harvesting bone for grafting applications. A
      handheld instrument is described that cuts and collects thin shavings of bone
      from cortical surfaces. MATERIALS AND METHODS: This study included 193
      consecutive patients who needed bone augmentation and simultaneous implant
      placement in the severely atrophic posterior maxilla and in the anterior maxilla
      with acquired defect of alveolar bone as a result of local trauma. A total of 477
      implants were placed. Clinical criteria for evaluation at time of implant
      exposure included stability in all directions, crestal bone resorption, and any
      reported pain of discomfort. RESULTS: There were no failures of the anterior
      maxilla group, and no signs of bone resorption were noted at the second stage
      surgery or during the follow-up. During initial and late healing, there was no
      dehiscence of the soft tissue flaps and no membranes were exposed. Core biopsies
      typically showed immature, newly formed bone and, on average, 27% to 36% vital
      bone. CONCLUSION: From this research, it appears that excellent implant success
      rates can be achieved in grafted sinuses or ridges when a locally harvested
      autogenous bone graft with a ribbon geometry is used.

PMID- 15573356
TI  - Microbiology and management of peritonsillar, retropharyngeal, and parapharyngeal
      abscesses.
AB  - This review describes the microbiology, diagnosis, and management of
      peritonsillar, retropharyngeal, and parapharyngeal abscesses in children.
      Predominant anaerobic organisms isolated in peritonsillar, lateral pharyngeal,
      and retropharyngeal abscesses are Prevotella, Porphyromonas, Fusobacterium and
      Peptostreptococcus spp.; aerobic organisms are group A streptococcus (
      Streptococcus pyogenes ), Staphylococcus aureus and Haemophilus influenzae .
      Anaerobic bacteria can be isolated from most abscesses whenever appropriate
      techniques for their cultivation have been used, while S. pyogenes is isolated in
      only about one third of cases. More than two thirds of deep neck abscesses
      contain beta-lactamase producing organisms. Management of tonsillar,
      peritonsillar, and retropharyngeal abscesses is similar. Systemic antimicrobial
      therapy should be given in large doses whenever the diagnosis is made. However,
      when pus is formed, antimicrobial therapy is effective only in conjunction with
      adequate surgical drainage. Untreated abscesses can rupture spontaneously into
      the pharynx, causing catastrophic aspiration. Other complications are extension
      of infection laterally to the side of the neck or dissection into the posterior
      mediastinum through facial planes and the prevertebral space. Death can occur
      from aspiration, airway obstruction, erosion into major blood vessels, or
      extension to the mediastinum.

PMID- 15573357
TI  - Tumoral calcinosis of the articular disc of the temporomandibular joint: a rare
      entity.

PMID- 15573358
TI  - Use of recombinant plasma kallikrein inhibitor in hereditary angioedema: a case
      report and review of the management of the disorder.

PMID- 15573359
TI  - Arteriovenous fistula after mandibular condylar fracture.

PMID- 15573360
TI  - Mucosal preservation in the treatment of mucocele with CO2 laser.

PMID- 15573361
TI  - Bis-phossy jaw, phossy jaw, and the 21st century: bisphosphonate-associated
      complications of the jaws.

PMID- 15573362
TI  - Usage of the term "ascending ramus".

PMID- 15573363
TI  - Campaigning the way it should be.

PMID- 15573364
TI  - NO spin trapping and EPR studies on the photochemistry of aliphatic aldehydes.
AB  - Radicals, such as acyl, hydrated acyl, alkyl and ketyl radicals, from aliphatic
      aldehyde photochemistry were detected by NO spin trapping and EPR techniques.
      Deuterium effects on EPR spectra and the generation of radicals by 2-amido-2
      propyl radical attack on substrate molecules in aqueous solution via hydrogen
      atom abstraction were applied to identify radicals produced photochemically from
      aldehydes. Aliphatic aldehydes used in the present investigation were
      formaldehyde, acetaldehyde, acetaldehyde-d4, propionaldehyde, isobutyraldehyde,
      isopentanal and tert-pentanal. Possible reaction mechanisms are suggested.

PMID- 15573365
TI  - Modern management of salivary calculi.
AB  - BACKGROUND: The aim was to investigate the results of a minimally invasive
      approach to the management of salivary calculi. METHODS: Four hundred and fifty
      five salivary calculi (323 submandibular and 132 parotid) were treated using
      extracorporeal shock-wave lithotripsy (ECSWL), fluoroscopically guided basket
      retrieval or intraoral stone removal under general anaesthesia. The techniques
      were used either alone or in combination. RESULTS: ECSWL achieved complete
      success (stone and symptom free) in 87 (39.4 percent) of 221 patients (84 of 218
      primary and all of three secondary procedures; 43 of 131 submandibular, 44 of 90
      parotid). Basket retrieval cured 124 (74.7 percent) of 166 patients (103 of 136
      primary and 21 of 30 secondary procedures; 80 of 109 submandibular, 44 of 57
      parotid). Intraoral surgical removal was successful in a further 137 (95.8
      percent) of 143 patients with submandibular stones (99 of 101 primary, 36 of 38
      secondary and two of four tertiary procedures). The overall success rate for the
      three techniques was 348 (76.5 percent) of 455. CONCLUSION: A minimally invasive
      approach to the management of salivary calculi is to be encouraged. All three
      techniques described have low morbidity and afford the possibility of retaining a
      functional gland.

PMID- 15573366
TI  - Conventional bilateral cervical exploration versus open minimally invasive
      parathyroidectomy under local anaesthesia for primary hyperparathyroidism.
AB  - BACKGROUND: Minimally invasive parathyroidectomy (MIP) has been introduced for
      the treatment of patients with primary hyperparathyroidism (pHPT). Thus far, only
      one randomized trial has compared video-assisted MIP with conventional bilateral
      cervical exploration (BCE). The value of open MIP is therefore not known.
      METHODS: Fifty patients with a solitary parathyroid adenoma localized before
      surgery by sestamibi scintigraphy were randomized to undergo BCE under general
      anaesthesia (n = 25) or targeted MIP via a 2-cm incision using local anaesthesia
      (n = 25). Postoperative hypocalcaemia was the primary endpoint. Secondary outcome
      measures were operating time, complications, postoperative analgesia and
      recurrent disease. Follow-up was carried out at 1 and 6 months. RESULTS: All
      patients who underwent BCE and 24 of those who had MIP were cured by the primary
      operation. Operating time was 22 min shorter in the MIP group (P = 0.024). Serum
      levels of calcium were slightly lower during the first 4 days after surgery in
      the BCE group (P = 0.022). No other no significant differences were found.
      CONCLUSION: Targeted MIP using local anaesthesia reduces operating time and
      causes less postoperative biochemical hypocalcaemia compared with bilateral neck
      exploration.

PMID- 15573367
TI  - Specific detection of O-linked N-acetylhexosamine modified peptides using
      multiple precursor ion scans.

PMID- 15573368
TI  - Electrospray ionization quadrupole time-of-flight and matrix-assisted laser
      desorption/ionization tandem time-of-flight mass spectrometric analyses to solve
      micro-heterogeneity in post-translationally modified peptides from Phoneutria
      nigriventer (Aranea, Ctenidae) venom.
AB  - Previous studies of the fractionated venom of the Brazilian armed spider
      Phoneutria nigriventer, obtained by gel filtration, have demonstrated the
      presence of a fraction PhM, a pool of small peptides (up to 2000 Da) that provoke
      contractions in smooth muscle of guinea pig ileum. Initial attempts to sequence
      these peptides were largely unsuccessful because of the low purification yield
      and the fact that the majority seemed to be blocked at their N-termini. In the
      present work, analysis of this venom fraction by mass spectrometry has revealed
      the existence of a highly complex mixture of peptides with molecular weights
      corresponding to those observed for the muscle-active peptides previously
      described (800-1800 Da). These peptides appear to be a family of isoforms with
      some particular features. The amino acid sequences of 15 isoforms have been
      determined by tandem mass spectrometry (MS/MS) using both electrospray ionization
      quadrupole time-of-flight mass spectrometry (ESI-Q/ToFMS) and matrix-assisted
      laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI
      ToF/ToFMS). These molecules contain post-translational modifications such as
      proteolysis and C-terminal amidation, which combine to generate additional
      isoforms. All the isoforms sequenced in this study possess an N-terminal
      pyroglutamic acid residue. A search for sequence similarities with other peptides
      in databanks revealed that these peptides are structurally related to the
      tachykinins, a family of neuro-hormone peptides. The data obtained in this study
      will be essential for the subsequent steps of this research, the synthesis of
      these peptides and pharmacological characterization of their biological activity.

PMID- 15573369
TI  - Original and reviewed nuclear grading according to the Fuhrman system: a
      multivariate analysis of 388 patients with conventional renal cell carcinoma.
AB  - BACKGROUND: The objective of the current study was to evaluate the
      reproducibility of the Fuhrman nuclear grading system as well as its independent
      predictive value in a series of patients with conventional renal cell carcinoma
      (RCC). METHODS: The authors selected 388 patients who had undergone surgical
      treatment for conventional RCC between 1986 and 2000. Pathology slides from the
      selected patients were reviewed by a single pathologist, who reassigned a Fuhrman
      nuclear grade and assessed the presence of tumor necrosis. The pathologist was
      blinded to both the original pathologic diagnosis and follow-up data. The kappa
      statistic was used to evaluate concordance between original and reviewed nuclear
      grades. The log-rank test was used for univariate analyses, and a Cox
      proportional hazards model was used for multivariate analyses. RESULTS: The
      original Fuhrman nuclear grade was Grade 1 (G1) in 111 patients (28.6%), G2 in
      141 patients (36.3%), G3 in 108 patients (27.8%), and G4 in 28 patients (7.3%).
      After pathology slide review, nuclear grades were reassigned as follows: G1 in 49
      patients (12.6%), G2 in 138 patients (35.6%), G3 in 150 patients (38.7%), and G4
      in 51 patients (13.1%). The grade of concordance was moderate (kappa=0.44; P
      <0.001). Univariate analyses identified three separate prognostic categories
      defined by nuclear grade (G1 and G2 vs. G3 vs. G4). Both the original and the
      reviewed Fuhrman nuclear grading systems were capable of independently predicting
      disease-specific survival in patients with conventional RCC. CONCLUSIONS: The
      interobserver reproducibility of Fuhrman nuclear grading was moderate. The
      substantial overlap in survival curves for G1 and G2 tumors provided an
      opportunity to cluster those categories, and the resulting three-tiered nuclear
      grading system was an independent predictor of cause-specific survival in
      patients with conventional RCC. Other independent predictors of survival included
      pathologic stage and tumor necrosis status.

PMID- 15573370
TI  - A different pattern of cytotoxic T lymphocyte recognition against primary and
      metastatic tumor cells in a patient with nonsmall cell lung carcinoma.
AB  - BACKGROUND: Lung carcinoma represents the most frequent cause of cancer death
      worldwide because of tumor metastases. The objective of the current study was to
      analyze the immunologic response during the progress of lung carcinoma
      metastasis. METHODS: The authors established two tumor cell lines that were
      derived from primary and metastatic lesions in a patient with lung carcinoma
      (Patient G603). One cell line (G603L) was established from the primary lesion,
      and the other cell line (G603AD) was established from a metastatic lesion in the
      right adrenal gland 7 months after the patient underwent surgery for the primary
      lesion. Autologous regional lymph node lymphocytes were stimulated with CD80
      transfected G603L cells, then cytotoxic T lymphocytes (CTLs) were induced against
      both lung carcinoma cell lines. RESULTS: Both G603L cells and G603AD cells
      expressed Class I human leukocyte antigen, intracellular cell adhesion molecule
      1, and lymphocyte-associated antigen type 3 (LFA-3), but not Fas or Fas ligand on
      their surfaces. By stimulation with CD80-transfected G603L cells, 2 CTL clones
      (H2/17 and H2/36) were established from the bulk CTLs. CTL clone H2/17 lysed
      G603L cells but not G603AD cells, suggesting that the antigen recognized by CTL
      clone H2/17 was abrogated during the process of metastasis. In contrast, CTL
      clone H2/36 lysed both G603L cells and G603AD cells, indicating that the antigen
      recognized by CTL clone H2/36 was maintained in the tumor cells throughout tumor
      progression. CONCLUSIONS: The results demonstrated the possibility that some
      tumor-associated antigens may be abrogated during the process of metastasis,
      although others are maintained. The identification of these antigens will lead to
      a better understanding of their immunologic role during disease progression in
      patients with lung carcinoma.

PMID- 15573371
TI  - Transient inflammatory response induced by apoptotic cells is an important
      mediator of melanoma cell engraftment and growth.
AB  - Two murine melanoma cell lines, Tm1 and Tm5, were derived from a nontumorigenic
      lineage of pigmented murine melanocytes, melan-a. Both Tm1 and Tm5 are invariably
      tumorigenic in syngeneic mice when inoculated s.c. in doses higher than 10(4)
      cells; 10(3) or fewer cells rarely give rise to tumors. We demonstrate that
      subtumorigenic inocula of Tm1 or Tm5 cells (10(3)) as well as of a known murine
      melanoma cell line (B16F10) develop as vigorously growing tumor grafts only when
      coinoculated with apoptotic, but not necrotic cells. The presence of apoptotic
      cells correlates with a transient inflammatory infiltrate, composed mainly of
      neutrophils and macrophages. Kinin B1 receptor-deficient mice, which have
      impaired transmigration of neutrophils to inflamed tissues, had significant
      growth inhibition of subtumorigenic doses of melanoma cells coinjected with
      apoptotic cells. Using the same model, tumor take in athymic mice was similar to
      that seen in wild-type mice, suggesting that a T cell-dependent inflammatory
      response is not necessary to promote the survival and growth of subtumorigenic
      doses of melanoma cells. Taken together, our results describe how tumor
      engraftment and growth can be profoundly affected by microenvironmental
      alterations in response to the presence of apoptotic cells. Disrupting the
      delicate balance between apoptotic cells and leukocyte infiltration may provide
      potentially important insights for understanding and interfering with tumor cell
      viability during treatment with either gamma-radiation or apoptosis-inducing
      drugs.

PMID- 15573372
TI  - Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline
      concentration: a comparison with sugar permeability tests.
AB  - BACKGROUND: Intestinal mucositis is an important cause of cancer treatment
      related morbidity and mortality, carrying a serious economic burden. Currently,
      objective parameters are lacking that would enable the monitoring of gut damage
      in routine clinical practice, thus hindering the development of clinical studies
      designed to investigate potential new strategies aimed at reducing or preventing
      this side effect. The authors investigated the characteristics of serum
      citrulline concentration compared with sugar permeability tests with respect to
      its use as a marker for cancer treatment-induced small bowel injury. METHODS: In
      this prospective study, 10 patients with hematologic malignancies who were
      receiving myeloablative therapy had gut toxicity assessed with sugar permeability
      tests. Serum citrulline concentrations also were determined using archival serum
      samples. The association between both parameters and their respective
      characteristics were analyzed and compared with data from the literature.
      RESULTS: Sensitivity and specificity were better for the citrulline assay
      compared with sugar permeability tests. Maximum gut damage assessed with the
      citrulline assay was observed 1-2 weeks earlier compared with the sugar
      permeability test. Similarly, citrulline indicated recovery of gut damage at 3
      weeks after transplantation, whereas most sugar permeability tests remained
      abnormal. CONCLUSIONS: The simplicity of the method, the low costs, and the lack
      of drawbacks to the method make the citrulline assay the first choice for
      measuring and monitoring treatment-related gut damage and provides an objective
      parameter for cancer treatment-related gut toxicity.

PMID- 15573374
TI  - Effect of T-R conformational change on sickle-cell hemoglobin interactions and
      aggregation.
AB  - We compare the role of a conformational switch and that of a point mutation in
      the thermodynamic stability of a protein solution and in the consequent
      propensity toward aggregation. We study sickle-cell hemoglobin (HbS), the beta6
      Glu-Val point mutant of adult human hemoglobin (HbA), in its R (CO-liganded)
      conformation, and compare its aggregation properties to those of both HbS and HbA
      in their T (unliganded) conformation. Static and dynamic light scattering
      measurements performed for various hemoglobin concentrations showed critical
      divergences with mean field exponents as temperature was increased. This allowed
      determining spinodal data points T(S)(c) by extrapolation. These points were
      fitted to theoretical expressions of the T(S)(c) spinodal line, which delimits
      the region where the homogeneous solution becomes thermodynamically unstable
      against demixing in two sets of denser and dilute mesoscopic domains, while
      remaining still liquid. Fitting provided model-free numerical values of enthalpy
      and entropy parameters measuring the stability of solutions against demixing,
      namely, 93.2 kJ/mol and 314 J/ degrees K-mol, respectively. Aggregation was
      observed also for R-HbS, but in amorphous form and above physiological
      temperatures close to the spinodal, consistent with the role played in nucleation
      by anomalous fluctuations governed by the parameter epsilon = (T - T(S))/T(S).
      Fourier transform infrared (FTIR) and optical spectroscopy showed that
      aggregation is neither preceded nor followed by denaturation. Transient multiple
      interprotein contacts occur in the denser liquid domains for R-HbS, T-HbS, and T
      HbA. The distinct effects of their specific nature and configurations, and those
      of desolvation on the demixing and aggregation thermodynamics, and on the
      aggregate structure are highlighted.

PMID- 15573375
TI  - High affinity fucose binding of Pseudomonas aeruginosa lectin PA-IIL: 1.0 A
      resolution crystal structure of the complex combined with thermodynamics and
      computational chemistry approaches.
AB  - PA-IIL is a fucose-binding lectin from Pseudomonas aeruginosa that is closely
      related to the virulence factors of the bacterium. Previous structural studies
      have revealed a new carbohydrate-binding mode with direct involvement of two
      calcium ions (Mitchell E, Houles C, Sudakevitz D, Wimmerova M, Gautier C, Perez
      S, Wu AM, Gilboa-Garber N, Imberty A. Structural basis for selective recognition
      of oligosaccharides from cystic fibrosis patients by the lectin PA-IIL of
      Pseudomonas aeruginosa. Nat Struct Biol 2002;9:918-921). A combination of
      thermodynamic, structural, and computational methods has been used to study the
      basis of the high affinity for the monosaccharide ligand. A titration
      microcalorimetry study indicated that the high affinity is enthalpy driven. The
      crystal structure of the tetrameric PA-IIL in complex with fucose and calcium was
      refined to 1.0 A resolution and, in combination with modeling, allowed a proposal
      to be made for the hydrogen-bond network in the binding site. Calculations of
      partial charges using ab initio computational chemistry methods indicated that
      extensive delocalization of charges between the calcium ions, the side chains of
      the protein-binding site and the carbohydrate ligand is responsible for the high
      enthalpy of binding and therefore for the unusually high affinity observed for
      this unique mode of carbohydrate recognition.

PMID- 15573376
TI  - Fibroblast growth factor-2 regulates the synthesis of hyaluronan by human
      periodontal ligament cells.
AB  - Basic fibroblast growth factor (FGF-2) can enhance biological potentials of
      periodontal ligament cells and its topical application induces considerable
      periodontal tissue regeneration in vivo. In this study, we examined the effect of
      FGF-2 on the production of hyaluronan (HA), an extracellular matrix playing
      important roles in homeostasis and inflammatory/wound healing responses, by human
      periodontal ligament (HPDL) cells. An inhibition binding-protein assay revealed
      that FGF-2 significantly increased HA production by HPDL cells in a dose
      dependent manner. Analysis by HPLC revealed that in conditioned medium of FGF-2
      treated HPDL cells HA had a higher molecular mass, compared to that of untreated
      HPDL cells. RT-PCR analysis revealed the enhancement of mRNA expression of
      hyaluronan synthase (HAS) 1 and HAS 2, both of which contribute to the production
      of HA with a high molecular mass, but not HAS 3 in the FGF-2-treated HPDL cells.
      In contrast, three isoforms of hyaluronidase (HYAL) transcript were unchanged in
      the FGF-2-treated HPDL cells. These results provide new evidence for the possible
      involvement of FGF-2 in the regulation of HA production and its appreciable roles
      in not only homeostasis but also regeneration of periodontal tissues.

PMID- 15573377
TI  - The agnoprotein of polyomaviruses: a multifunctional auxiliary protein.
AB  - The late region of the three primate polyomaviruses (JCV, BKV, and SV40) encodes
      a small, highly basic protein known as agnoprotein. While much attention during
      the last two decades has focused on the transforming proteins encoded by the
      early region (small and large T-antigens), it has become increasingly evident
      that agnoprotein has a critical role in the regulation of viral gene expression
      and replication, and in the modulation of certain important host cell functions
      including cell cycle progression and DNA repair. The importance of agnoprotein is
      underscored by its expression during lytic infection of glial cells by JCV that
      occurs in progressive multifocal leukoencephalopathy (PML), and also in some JCV
      associated human neural tumors particularly medulloblastoma. In this review, we
      will discuss the structure and function of agnoprotein in the viral life cycle
      during the course of lytic infection and the consequences of agnoprotein
      expression for the host cell.

PMID- 15573378
TI  - Smad function and intranuclear targeting share a Runx2 motif required for
      osteogenic lineage induction and BMP2 responsive transcription.
AB  - The coordinated activity of Runx2 and BMP/TGFbeta-activated Smads is critical for
      formation of the skeleton, but the precise structural basis for the Runx2/Smad
      interaction has not been resolved. By deletion mutagenesis, we have defined the
      Runx2 motif required for physical and functional interaction with either BMP or
      TGFbeta responsive Smads. Smad responsive transcriptional activity was retained
      upon deletion of the C-terminus to amino acid (aa) 432 but lost with deletion to
      aa 391. Thus the Smad interacting domain (SMID) of Runx2 (432-391) is embedded in
      the well-defined nuclear matrix targeting signal (NMTS) that mediates
      intranuclear trafficking. The SMID suffices as an interacting module when fused
      to the heterologous Gal-4 protein. Formation of the Runx2 and Smad complex is
      dependent on Runx2 phosphorylation through the MAPK signaling pathway, as
      determined by co-immunoprecipitation studies. We established that all SMID/NMTS
      deficient Runx2 mutants do not show in situ association with Smad in the nucleus
      nor do they support BMP2-mediated osteogenic induction of the mesenchymal C2C12
      cell line. Thus, we provide direct evidence that the SMID/NMTS domain (391-432)
      of Runx2 is essential for BMP2-mediated osteoblast differentiation. Our findings
      suggest that TGFbeta/ BMP2 signaling, MAPK dependent phosphorylation, and Runx2
      subnuclear targeting converge to induce the osteogenic phenotype.

PMID- 15573379
TI  - Urokinase plasminogen activator receptor promotes macrophage infiltration into
      the vascular wall of ApoE deficient mice.
AB  - The urokinase plasminogen activator receptor (uPAR) regulates macrophage adhesion
      and migration by binding directly to matrix proteins and signaling through
      integrin complexes. In this study, we examined the role of uPAR on macrophage
      infiltration into the vascular wall. Stable murine macrophage (Raw264.7) cell
      lines expressing high levels of human uPAR, human urokinase plasminogen activator
      (uPA), or both were established using expression vectors driven by the human CD68
      promoter. Stimulation with human uPA specifically induced phosphorylation of
      early response regulated kinase (ERK) in cells expressing human uPAR but not in
      sham transfected cells. The human uPAR expressing Raw264.7 cells showed increased
      adhesion to both human uPA and vitronectin (Vn). Raw264.7 cells expressing human
      uPAR or both human uPAR and uPA, but not uPA alone, were detected in the aortic
      wall of ApoE(-/-) mice, and no cells were detected in that of age-matched
      C57BL/6J mice after intravenous infusion of the cells. Blocking of Mac-1/ICAM-1
      interaction by anti-alphaM antibody (M1/70) significantly reduced the
      infiltration of huPAR-expressing Raw264.1 cells into aorta of ApoE(-/-) mice.
      Treatment of C57BL/6J mice with angiotensin II resulted in infiltration of
      Raw264.7 cells expressing human uPAR. These data demonstrate that uPAR plays a
      key role in promoting macrophage infiltration into the arterial wall of ApoE(-/-)
      mice.

PMID- 15573380
TI  - Elucidation of information encoded in tryptophan 140 of staphylococcal nuclease.
AB  - We investigated the role of W140 in the folding of Staphylococcal nuclease. For
      this purpose, we constructed the 19 possible substitution mutations at residue
      140. Only three mutants, W140F, W140H, and W140Y, adopted native-like structures
      under physiological conditions and showed native-like enzymatic activities. In
      contrast, the other 16 mutants took on compact unfolded structures under
      physiological conditions and the enzymatic activities of these mutants were
      decreased to approximately 70% of wild-type levels. These 16 mutants maintained
      substrate-induced foldability. These results strongly indicate that the side
      chain information encoded by residue 140 is essential to maintain a stable native
      structure, and that this residue must be an aromatic side chain. The order of
      thermal stability was wild type > W140H > W140F = W140Y. Therefore, the five
      membered nitrogen-containing ring of the indole is thought to bear the essential
      information. In the crystal structure of staphylococcal nuclease, the five
      membered ring is at the local center of the C-terminal cluster through
      hydrophobic interactions. This cluster plays a key role in the interaction
      connecting the C-terminal region and the N-terminal beta-core. Mutants other than
      W140H, W140F, and W140Y lost the ability to form the local core, which caused the
      loss of the long-range interactions between the C-terminal and N-terminal
      regions. Inhibitor or substrate binding to these mutants compensates for the lack
      of long-range interactions generated by W140.

PMID- 15573381
TI  - HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates
      c-FLIP in lymphoid T cells: a potential molecular mechanism to escape TRAIL
      cytotoxicity.
AB  - In this study, we showed the existence of a positive correlation between the
      amount of human immunodeficiency virus-type 1 (HIV-1) RNA in HIV-1 seropositive
      subjects and the plasma levels of TRAIL. Since it has been previously
      demonstrated that HIV-1 Tat protein up-regulates the expression of TRAIL in
      monocytic cells whereas tat-expressing lymphoid cells are more resistant to TRAIL
      cytotoxicity, we next investigated the effect of Tat on the expression/activity
      of both apical caspase-8 and -10, which play a key role in mediating the initial
      phases of apoptosis by TRAIL, and c-FLIP. Jurkat lymphoblastoid human T cell
      lines stably transfected with a plasmid expressing wild-type (HIV-1) tat gene
      showed normal levels of caspase-8 but significantly decreased levels of caspase
      10 at both mRNA and protein levels with respect to Jurkat transfected with the
      control plasmid or with a mutated (cys22) non-functional tat cDNA. A significant
      decrease of caspase-10 expression/activity was also observed in transient
      transfection experiments with plasmid carrying tat cDNA. Moreover, c-FLIP(L) and
      c-FLIP(S) isoforms were up-regulated in tat-expressing cells at both mRNA and
      protein level in comparison with control cells. Taken together, these results
      provide a molecular basis to explain the resistance of tat-expressing Jurkat
      cells to apoptosis induced by TRAIL and, possibly, to other death-inducing
      ligands.

PMID- 15573382
TI  - Is the histomorphological concept of the female pelvic floor and its changes due
      to age and vaginal delivery correct?
AB  - AIMS: To compare the histomorphology of pelvic floor specimens of 94 female
      cadavers, ten male cadavers, and 24 female symptomatic patients who underwent
      pelvic floor surgery, and to evaluate the association of age, parity, and sex to
      myogenic and/or neurogenic changes to the levator ani muscle (LAM). METHODS: The
      pelvic floor was biopsied at the pubococcygeus, the iliococcygeus and the
      coccygeus muscle. After staining, signs for myogenic/neurogenic changes to the
      muscle were evaluated (fibrosis, variation in fiber diameter, centralization of
      nuclei, small angulated fibers, and type grouping). To identify the intact
      neuromuscular junction stainings with NCAM (neuronal cell adhesion molecule) and
      acetylcholinesterase (ACE) were used. RESULTS: A significant influence of age and
      parity on the histomorphological criteria of myogenic cell-damage was shown in
      this study. Although these criteria were found even in young nulliparous women,
      there was a significant increase in older or parous women with at least one
      vaginal delivery. We failed to demonstrate significant changes between the
      nulliparous LAM, the male LAM, and the LAM from women with prolapse and
      incontinence. None of the specimen showed any obvious evidence of neuropathy.
      CONCLUSIONS: We have evaluated histological criteria adapted from the examination
      of limb muscles in the LAM of nulliparous young women. "Myogenic changes" seem to
      be a normal finding in the LAM. The increase of these changes with aging and
      parity points to mechanical stress to the LAM as the most plausible causative
      factor. We propose that further studies using histomorphological techniques of
      the pelvic floor muscle in nulliparous and parous women should clarify the
      potential role of our histological findings.

PMID- 15573383
TI  - Structure and dynamics of the human pleckstrin DEP domain: distinct molecular
      features of a novel DEP domain subfamily.
AB  - Pleckstrin1 is a major substrate for protein kinase C in platelets and
      leukocytes, and comprises a central DEP (disheveled, Egl-10, pleckstrin) domain,
      which is flanked by two PH (pleckstrin homology) domains. DEP domains display a
      unique alpha/beta fold and have been implicated in membrane binding utilizing
      different mechanisms. Using multiple sequence alignments and phylogenetic tree
      reconstructions, we find that 6 subfamilies of the DEP domain exist, of which
      pleckstrin represents a novel and distinct subfamily. To clarify structural
      determinants of the DEP fold and to gain further insight into the role of the DEP
      domain, we determined the three-dimensional structure of the pleckstrin DEP
      domain using heteronuclear NMR spectroscopy. Pleckstrin DEP shares main
      structural features with the DEP domains of disheveled and Epac, which belong to
      different DEP subfamilies. However, the pleckstrin DEP fold is distinct from
      these structures and contains an additional, short helix alpha4 inserted in the
      beta4-beta5 loop that exhibits increased backbone mobility as judged by NMR
      relaxation measurements. Based on sequence conservation, the helix alpha4 may
      also be present in the DEP domains of regulator of G-protein signaling (RGS)
      proteins, which are members of the same DEP subfamily. In pleckstrin, the DEP
      domain is surrounded by two PH domains. Structural analysis and charge
      complementarity suggest that the DEP domain may interact with the N-terminal PH
      domain in pleckstrin. Phosphorylation of the PH-DEP linker, which is required for
      pleckstrin function, could regulate such an intramolecular interaction. This
      suggests a role of the pleckstrin DEP domain in intramolecular domain
      interactions, which is distinct from the functions of other DEP domain
      subfamilies found so far.

PMID- 15573384
TI  - Evaluation of urinary and general symptoms and correlation with other clinical
      parameters in interstitial cystitis patients.
AB  - AIMS: Interstitial cystitis (IC) has been deemed by some authors as a local
      manifestation of a systemic disease, particularly one of the autoimmune
      disorders. In order to provide an answer to the question whether IC patients do
      or do not indiscriminately report high scores for various somatic symptoms, we
      compared University of Wisconsin scores (U-W scores), including both urinary and
      non-urinary symptoms, for 30 IC female patients and 30 female controls. MATERIALS
      AND METHODS: A total of 30 female patients with IC and 30 healthy female controls
      were recruited for the study. All patients had to meet the symptom criteria
      established by the National Institute for Diabetes and Digestive and Kidney
      Diseases. Each patient completed a University of Wisconsin symptom scale, after
      translation (WICS). RESULTS: In the IC group median score was zero for all, but
      two of the reference symptoms: abdominal cramps and dizziness. All urinary
      symptoms were significantly increased in IC patients compared to controls. In the
      control group, the median value of urinary symptoms was zero. The duration of the
      disease was then related to IC symptoms in the patient group. Among the bladder
      related symptoms, a good correlation was found for several specific symptoms and
      urinary symptoms as a whole. An association could be found between a positive
      potassium sensitivity test (PST) and burning bladder sensation, as well as pelvic
      discomfort. CONCLUSIONS: IC patients had significantly higher scores for the
      seven urinary symptoms compared to controls. The duration of disease was found to
      be correlated with the group of seven urinary symptoms.

PMID- 15573385
TI  - Costs of managing urinary and faecal incontinence in a sub-acute care facility: a
      "bottom-up" approach.
AB  - AIMS: To measure accurately the direct costs of managing urinary and faecal
      incontinence in the sub-acute care setting. MATERIALS AND METHODS: Prospective
      observational study was undertaken in two sub-acute care units in a metropolitan
      hospital. A consecutive series of 29 consecutive patients with urinary and/or
      faecal incontinence, who were in-patients in a geriatric rehabilitation or sub
      acute neurologic unit underwent routine timed voiding protocol, as per usual
      care. Face-to-face bedside recordings of all incontinence care, with detailed
      cost analysis, were undertaken. RESULTS: A total of 3,621 occasions of continence
      care were costed. The median time per 24 hr spent caring for incontinence per
      patient was 109 min (interquartile range 88-140). Isolated urinary incontinence
      episodes occurred in 28 patients (96.5%), mixed urinary/faecal incontinence
      episodes observed in 79.3%, and episodes of pure faecal incontinence were seen in
      62%. The median costs of incontinence care in the sub-acute setting was $49AU per
      24 hr, the major share ($41) spent on staff wages. The incontinence tasks of
      toileting assistance, pad changes, bed changes and catheter care were spread
      evenly across the three 8 hr shifts of duty. CONCLUSIONS: As our population
      demographics include an increasingly greater portion of the elderly, for whom
      long term institutional care is becoming relatively more scarce, provision of
      care in the sub-acute unit that may allow rehabilitation and return to home
      warrants scrutiny. This is the first study that delineates the costs of managing
      urinary and faecal incontinence in the sub-acute care setting. Such costs are
      substantial and place a heavy burden upon night-time carers.

PMID- 15573386
TI  - CFTR: more than just a chloride channel.
AB  - This review examines the cystic fibrosis transmembrane conductance regulator
      (CFTR) protein. After summarizing the ion channels regulated by CFTR, the review
      focuses on the functions of CFTR that do not relate directly to a disease
      mechanism based on a channelopathy. The key concept is that newly synthesized
      CFTR has to enter lipid vesicles which bud from the endoplasmic reticulum. This
      is abnormally low in DeltaF508 CFTR. Normal wild type vesicular CFTR enters a
      recycling pool of lipid vesicles which transiently dock with the apical membrane
      only for CFTR to be retrieved shortly after into a sub-apical recycling
      compartment. This retrieval is abnormally fast in DeltaF508 CFTR. The review
      discusses the relationship between this process and the difficult topic of fat
      metabolism and then explores the possible links between abnormal fatty acid
      turnover and inflammatory cascades that are abnormal in cystic fibrosis. Finally
      the review concentrates on the emerging functions of a protein kinase (AMP
      activated kinase) which is bound near the C terminus of the CFTR protein whose
      functions could intergrate some of the abnormalities in lipid metabolism that
      result from mislocalization of CFTR in clinical disease.

PMID- 15573387
TI  - Periodic limb movements in sleep after a small deep subcortical infarct.

PMID- 15573388
TI  - Microalbuminuria as a screening tool in cystic fibrosis-related diabetes.
AB  - The improving longevity of cystic fibrosis (CF) subjects has resulted in an
      increased prevalence and duration of cystic fibrosis-related diabetes (CFRD).
      Microvascular complications were reported in CFRD. Microalbuminuria is well
      established as a sensitive indicator of progression to diabetic nephropathy in
      non-CF diabetes, but confounding factors may make it less sensitive for CF
      subjects. We performed a cross-sectional study to look for the presence of
      microalbuminuria in samples from 40 CF subjects (34 without diabetes; CFND)
      attending the Exeter CF Clinic, compared with 43 nondiabetic, non-CF controls.
      The albumin-creatinine ratio (ACR) was raised in CF subjects both with (P <
      0.001) and without (P < 0.0001) diabetes compared to controls. This reflected an
      increase in urinary albumin and a reduction in urinary creatinine in CF subjects.
      In single samples, microalbuminuria was present in 66.7%, 32.4%, and 15.4% of
      subjects in CFRD, CFND, and control groups. Repeat samples showed that 12% of
      CFND subjects and 17% of CFRD subjects met the criteria for a diagnosis of
      persistent microalbuminuria. In conclusion, CF subjects, even when not diabetic,
      have increased urinary albumin excretion due to chronic infection, and reduced
      urinary creatinine excretion due to low muscle mass. This results in subjects,
      who are not developing diabetic nephropathy, meeting the conventional criteria
      for microalbuminuria. We feel that further studies are required to clarify
      whether this measure is a useful tool to predict progression to diabetic
      nephropathy in subjects with CFRD.

PMID- 15573389
TI  - Beyond chloride transport: CFTR in the 21st century-introductory remarks to a new
      state of the art series.
AB  - This new series of articles on cystic fibrosis provides an overview of the
      confusing plethora of problems that arise from the loss of function in a low
      abundance protein, the cystic fibrosis membrane conductance regulator CFTR. The
      references are designed to take the clinical reader into areas and journals that
      they might not normally read. In particular we have concentrated on recent
      advances that suggest CFTR has functions that do not relate to chloride transport
      alone. In forthcoming issues of the journal the topics covered range from
      prospects and difficulties in the translation of new therapies into clinical
      practice, the regulation of the defective gene (promoters, enhancers, silencers,
      etc.), regulation and interaction of the CFTR protein product with other proteins
      in the cell, to functional approaches using developmental and secretory
      paradigms. These themes have been chosen to bring controversies at the cutting
      edge of cystic fibrosis research to the practicing pulmonologist in order to
      stimulate lateral thinking, which we hope will ultimately benefit our patients.

PMID- 15573390
TI  - Foreign-body aspiration mimicking congenital lobar emphysema in a forty-eight-day
      old girl.
AB  - Foreign-body aspiration (FBA) is a commonly encountered serious problem during
      childhood, accounting for 7% of lethal accidents in children aged 1-3 years.
      Bronchoscopy is indicated when a clear history of FBA is present, but the history
      may be unreliable. Clinical manifestations can be seen in various diseases, and
      when a history of FBA cannot be obtained, radiologic findings such as
      hyperaeration can suggest the presence of congenital anomalies, e.g., congenital
      lobar emphysema. Here, a 48-day-old girl with coconut aspiration is described, to
      emphasize that a clinical history may not be available and FBA should be among
      the possible diagnoses, even before 6 months of age.

PMID- 15573391
TI  - Medical management of parapneumonic pleural disease.
AB  - Considerable heterogeneity exists in the management of parapneumonic pleural
      disease. A randomized controlled trial (RCT) demonstrated the effectiveness of
      small-catheter drainage with fibrinolysis, but surgical devotees suggest this may
      only be applicable to "early" cases. We examined evidence-based medical
      management in "all-comers." We performed a retrospective database analysis of the
      management of all children with complex pleural effusion admitted to the John
      Radcliffe Hospital over the 7-year period 1996-2003. One hundred and ten children
      were admitted. Ten were excluded as they were part of a multicenter RCT and had
      received intrapleural saline instead of urokinase. Of the remaining 100, 51 were
      female and 49 male. Median age on admission was 5.8 years (range, 0.3-16.5).
      Symptoms preadmission averaged 11 days, with December the most common month for
      presentation. Ninety-six underwent chest ultrasound, confirming an effusion in
      all, described as loculated/septated (68) or echogenic (11). In 17 cases, no
      specific comment was made regarding the nature of the fluid seen on ultrasound.
      Ninety-five had subsequent chest tube drainage and then received intrapleural
      fibrinolysis with urokinase. An etiological organism was identified in 21 cases
      (21%) (Streptococcus pneumoniae in 10, group A Streptococcus in 5, Staphylococcus
      aureus in 4, Haemophilus influenzae in 1, and coliform in 1). In a further 9
      cases (9%), Gram-positive organisms were seen on pleural fluid microscopy, but
      did not grow on culture. Two (2%) required surgery due to the persistence of
      symptoms and an inadequate response to medical management. Median duration of
      admission was 7 days (range, 2-21 days); median duration of stay from
      intervention was 5 days (range, 2-19 days). At median follow-up of 8 weeks
      (range, 3-20 weeks), all children were symptom-free, with minimal pleural
      thickening on chest X-ray. In conclusion, antibiotic therapy with chest drain
      insertion and intrapleural urokinase is effective in treating complex
      parapneumonic effusion and is associated with a good long-term outcome.

PMID- 15573392
TI  - Relevance of a portable spirometer for detection of small airways obstruction.
AB  - While portable spirometers are increasingly used, little attention has been paid
      to test their validity for measurement of flows in small airways. The aim of this
      study was to compare the Spirotel portable spirometer to a laboratory spirometer
      (Jeager PFT), with regard to accuracy in measuring forced expiratory flows, and
      more specifically those influenced by small airways (FEF(25-75)). Fifty-nine
      children (mean age, 12 years; range, 7-17), were studied at baseline and after a
      bronchodilator inhalation. Spirometers were tested separately in a randomly
      designed order. A total of 117 sessions of flow-volume curves was performed with
      each spirometer. We obtained at least two acceptable and reproducible curves in
      88% and 76% of the sessions, with the laboratory and the portable spirometers,
      respectively. Unacceptable curves were easily detected by visual inspection of
      flow-time and flow-volume waveforms. Agreement was excellent between spirometers
      for the measurement of all expiratory flows, both at baseline and
      postbronchodilator. More specifically, agreement between spirometers was as high
      for measurements of FEF(25-75) (intraclass correlation coefficients 0.97) as for
      proximal flows. High correlations were found between baseline expiratory flows
      measured by each spirometer (and expressed as percent of predicted values), both
      in large and small airways (P < 0.001). The portable spirometer was highly
      sensitive for detecting small airways obstruction, as compared to the laboratory
      spirometer. Finally, the magnitudes of bronchodilator-related flow changes were
      also highly correlated, both in large and small airways (P < 0.001 and P = 0.004,
      respectively). We conclude that the Spirotel portable spirometer is reliable for
      measurement of forced expiratory flows, in large and small airways, provided that
      all curve waveforms can be stored and available for visual inspection.

PMID- 15573393
TI  - A new fiberoptical respiratory rate monitor for the neonatal intensive care unit.
AB  - A new technique for respiratory rate measurement in the neonatal intensive care
      unit, fiberoptic respirometry (FORE), was tested using a specially designed nasal
      adapter. The aim was to investigate the system's accuracy and compare it to the
      transthoracic impedance (TTI) method and manual counting (MC). Further, the
      relationship between accuracy and degree of body movement was investigated.
      Seventeen neonates of median gestational age 35 weeks were included in the study.
      Video recordings (synchronized with data recordings) were used for classification
      of body movement. Breaths per minute data were obtained for 23-32-min periods per
      child, and a subset of these included MC performed by experienced nurses. A Bland
      Altman analysis showed low accuracy of both FORE and TTI. A >20% deviation from
      MC was found in 22.7% and 23.8% of observations for the two methods,
      respectively. Both methods had accuracy problems during body movement. FORE
      tended to underestimate respiratory rate due to probe displacement, while TTI
      overestimated due to motion artefacts. The accuracy was also strongly subject
      dependent. The neonates were undisturbed by the FORE device. In some cases,
      though, it was difficult to keep the adapter positioned in the airway. Further
      development should, therefore, focus on FORE adapter improvements to maintain
      probe position over time.

PMID- 15573394
TI  - Exhaled nitric oxide is reduced in infants with rhinorrhea.
AB  - In infants, the effect of colds and other respiratory tract infections (RTI) on
      exhaled nitric oxide (FE(NO)) is not clear. In this study, we measured FE(NO) in
      24 infants (14 boys) who presented with rhinorrhea, with or without cough but not
      wheeze. Twelve of these infants had a history of recurrent wheeze. Levels were
      compared with a group of 23 healthy infants (13 boys). Further, 8 infants (5 with
      a history of recurrent wheeze) with rhinorrhea were tested after symptoms had
      resolved. Infants with rhinorrhea had significantly lower FE(NO) than the healthy
      infants (11.9 vs. 23.8 ppb, respectively, P < 0.0007). Levels increased from 7.5
      ppb to 34.1 ppb in the 8 infants tested with and without symptoms (P = 0.0002).
      Infants with rhinorrhea have reduced FE(NO), irrespective of their respiratory
      history.

PMID- 15573395
TI  - Randomized, double-blind, placebo-controlled, dose-escalating study of
      aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis
      lung disease.
AB  - Interferon gamma-1b (IFN-gamma1b) is a pleiotropic cytokine with immunomodulatory
      activities that could decrease bacterial burden, inflammation, and obstruction in
      patients with CF. Patients with CF (> or =12 years old, FEV1 > or =40% predicted)
      were randomly assigned to sequential dose cohorts inhaling 500 microg IFN
      gamma1b, 1,000 microg IFN-gamma1b, or placebo by Respirgard II nebulizer thrice
      weekly for 12 weeks. Sputum bacterial density and spirometry were measured.
      Safety, antibiotic use, hospitalization, and sputum neutrophils, elastase, DNA,
      IL-8, and myeloperoxidase were also evaluated. Sixty-six patients (mean age, 24
      years, with mean baseline FEV1 of 74 +/- 20 (SD) percent predicted) were studied.
      One patient had bronchospasm after the first dose of IFN-gamma1b; the overall
      withdrawal rate was 15% (5 in the placebo group, 2 in the 500-microg IFN-gamma1b
      group, and 3 in the 1,000 microg IFN-gamma1b group). The 500-microg IFN-gamma1b
      dose was well-tolerated, but the 1,000-mug dose cohort, who had a higher baseline
      bacterial density than placebo patients (mean difference, 1.2 log(10) CFU/g
      sputum, 95% confidence interval (CI), 0.1,2.8, P=0.04), had 24% more
      hospitalizations for exacerbation than placebo patients (95% CI, 2,45%, P=0.05).
      There was a 0.12-l difference between the 500-microg IFN-gamma1b and placebo
      groups with respect to the 12-week change in FEV1 (active group minus placebo
      group, 95% CI, -0.03,0.26, P=0.11), as compared to a 0.01-l difference between
      the 1,000-microg IFN-gamma1b and placebo groups (95% CI, -0.16,0.17, P=0.96). No
      effects of IFN-gamma1b were seen in sputum bacterial density or inflammatory
      biomarkers at 12 weeks. Aerosolized IFN-gamma1b did not improve pulmonary
      function, reduce sputum bacterial density, or affect inflammatory sputum markers
      in patients with mild-moderate lung disease.

PMID- 15573396
TI  - Ontogenesis of myosin light chain phosphorylation in guinea pig tracheal smooth
      muscle.
AB  - Increased airway responsiveness occurs in normal young individuals compared to
      adults. A maturation of airway smooth muscle (ASM) contractility is likely a
      mechanism of this juvenile airway hyperresponsiveness. Indeed, we showed in
      guinea pig tracheal smooth muscle (TSM) that maximum shortening velocity
      decreases dramatically after the first 3 weeks of life. Because the
      phosphorylation of the 20-kDa myosin light chain (MLC(20)) was shown to be a key
      event in ASM contractility, in the present work we sought to investigate it
      during ontogenesis. In three age groups (1-week-old, 3-week-old, and adult guinea
      pigs), we assessed the amount of MLC(20) phosphorylation achieved either in TSM
      crude protein homogenates exposed to Mg(2+) . ATP . CaCl(2) or in tracheal strips
      during electrical field stimulation (EFS). Phosphorylated and unphosphorylated
      MLC(20) were separated on nondenaturing 10% polyacrylamide gels, and the ratio of
      phosphorylation was obtained by densitometric analysis of chemiluminescent
      Western immunoblots. Maximum MLC(20) phosphorylation (% of total MLC(20)) in TSM
      tissue homogenate was, respectively, 32.6 +/- 5.7, 32.2 +/- 5.7, and 46.8 +/- 5.8
      in 1-week, 3-week, and adult guinea pigs. Interestingly, in nonstimulated intact
      tracheal strips, we found a substantial degree of MLC(20) phosphorylation:
      respectively, 42.2 +/- 5.8, 36.5 +/- 7.8, and 46.4 +/- 4.7 in 1-week, 3-week, and
      adult guinea pigs. Maximal EFS-induced MLC(20) phosphorylation (% increase over
      baseline) in the 3-week age group was attained after 3 sec of EFS, and was 161.2
      +/- 17.6, while in 1-week and adult guinea pigs, it was attained at 1.5 sec of
      EFS and was, respectively, 133.3 +/- 9.3 and 110.2 +/- 3.9 (P < 0.05). We
      conclude that MLC(20) phosphorylation in guinea pig intact tracheal strips
      correlates with ontogenetic changes in shortening velocity and changes in myosin
      light chain kinase content. These results further suggest that the maturation of
      ASM contractile properties plays a role in the greater airway responsiveness
      reported in children and young animals.

PMID- 15573397
TI  - Predicting protein functional sites with phylogenetic motifs.
AB  - In this report, we demonstrate that phylogenetic motifs, sequence regions
      conserving the overall familial phylogeny, represent a promising approach to
      protein functional site prediction. Across our structurally and functionally
      heterogeneous data set, phylogenetic motifs consistently correspond to functional
      sites defined by both surface loops and active site clefts. Additionally, the
      partially buried prosthetic group regions of cytochrome P450 and succinate
      dehydrogenase are identified as phylogenetic motifs. In nearly all instances,
      phylogenetic motifs are structurally clustered, despite little overall sequence
      proximity, around key functional site features. Based on calculated false
      positive expectations and standard motif identification methods, we show that
      phylogenetic motifs are generally conserved in sequence. This result implies that
      they can be considered motifs in the traditional sense as well. However, there
      are instances where phylogenetic motifs are not (overall) well conserved in
      sequence. This point is enticing, because it implies that phylogenetic motifs are
      able to identify key sequence regions that traditional motif-based approaches
      would not. Further, phylogenetic motif results are also shown to be consistent
      with evolutionary trace results, and bootstrapping is used to demonstrate tree
      significance.

PMID- 15573398
TI  - Human trabecular bone-derived osteoblasts support human osteoclast formation in
      vitro in a defined, serum-free medium.
AB  - While it has been assumed that osteoblasts in the human support osteoclast
      formation, in vitro evidence of this is currently lacking. We tested the ability
      of normal human trabecular bone-derived osteoblasts (NHBCs) to support osteoclast
      formation from human peripheral blood mononuclear cells (PBMC) in response to
      treatment with either 1alpha,25-dihydroxyvitamin D3 (1,25D) or parathyroid
      hormone (PTH), using a serum-replete medium previously used to support human
      osteoclast formation on a stroma of murine ST-2 cells. Under these conditions,
      NHBC did not support osteoclast formation, as assessed by morphological,
      histochemical, and functional criteria, despite our previous results
      demonstrating a link between induction of RANKL mRNA expression and NHBC
      phenotype in these media. We next tested a defined, serum-free medium (SDM) on
      NHBC phenotype, their expression of RANKL and OPG, and their ability to support
      osteoclast formation. SDM, containing dexamethasone (DEX) and 1,25D, induced
      phenotypic maturation of NHBC, based on the expression of STRO-1 and the
      bone/liver/kidney isoform of alkaline phosphatase (AP). PTH as a single factor
      did not induce phenotypic change. 1,25D and DEX induced the greatest ratio of
      RANKL:OPG mRNA, predictive of supporting osteoclast formation. Consistent with
      this, co-culture of NHBC with CD14+ PBMC, or bone marrow mononuclear cell (BMMC),
      or CD34+ BMMC precursors in SDM + 1,25D + DEX, resulted in functional osteoclast
      formation. Osteoclast formation also occurred in PTH + DEX stimulated co
      cultures. Interestingly, SDM supplemented with recombinant RANKL (25-100 ng/ml)
      and M-CSF (25 ng/ml), did not induce osteoclast formation from any of the
      osteoclast precursor populations in stromal-free cultures, unlike serum-replete
      medium. This study demonstrates that under the appropriate conditions, adult
      human primary osteoblasts can support de novo osteoclast formation, and this
      model will enable the detailed study of the role of both cell types in this
      process.

PMID- 15573399
TI  - Effect of ion exchange of glazed dental glass ceramics on strength parameters.
AB  - Ion exchange treatments can significantly increase the strength of dental glass
      ceramic core materials by induced compressive residual stresses. However, the
      core materials of dental restorations need to be veneered or at least to be
      stained and glazed for esthetic and functional reasons. The objective of this
      study was to determine the effect of different ion exchange treatments on the
      strength parameters of stained and glazed glass ceramics. Batches of specimens
      made of a leucite reinforced dental glass with and without staining and glazing
      layer, untreated, single ion exchanged (KNO3), and dual ion exchanged (1.
      KNO3/27, 2. 30 mol% NaNO3/70 mol% KNO3) were tested. The strength of the core
      material was increased from 117 to 213 MPa by single ion exchange. Staining and
      glazing increased the strength up to 165 MPa. Single ion exchange of the stained
      and glazed core caused only a slight additional strength increase up to 173 MPa.
      The dual ion exchanged stained and glazed core exhibit a strength of 195 MPa and
      decreased the large strength scatter because of a well-designed residual stress
      profile. We conclude that dual ion exchange treatments could significantly
      increase the mechanical reliability of stained and glazed glass ceramic
      restorations.

PMID- 15573400
TI  - Cellular and subcellular distribution of monocarboxylate transporters in cultured
      brain cells and in the adult brain.
AB  - Monocarboxylate transporters (MCTs) are involved in the uptake and release of
      lactate, pyruvate, and ketone bodies. Studies of their distribution at both the
      mRNA and protein levels have highlighted the specific expression of MCT1, MCT2,
      and more recently MCT4 in the central nervous system. MCT1 was found strongly
      expressed by cortical astrocytes both in vitro and in vivo. It was also found at
      high levels on blood vessels, ependymocytes, and glia limitans. A subset of
      neurons in vitro exhibited a weak but significant MCT1 expression. In contrast,
      it was determined that MCT2 represents the predominant neuronal MCT on cultured
      neurons as well as on neurons throughout the brain parenchyma. At the subcellular
      level, part of MCT2 is located in postsynaptic densities. Specific populations of
      astrocytes in the white matter also exhibited MCT2 expression in the rat, but not
      in the mouse brain. MCT4 was found exclusively in astrocytes in several areas
      including the cortex, the hippocampus, and the cerebellum. MCT2 expression
      increased in cultured neurons with days in vitro commensurate with increased
      synapse formation. Moreover, a significant increase in MCT2 expression was
      observed in cultured neurons exposed to noradrenaline, an effect involving a
      regulation at the translational level. The description of MCTs on different cell
      types in the central nervous system together with clear evidence for regulation
      of their expression further emphasize the important role that monocarboxylates,
      and particularly lactate, might play in brain energy metabolism not only during
      development but also in the adult.

PMID- 15573401
TI  - Bradykinin-induced p42/p44 MAPK phosphorylation and cell proliferation via Src,
      EGF receptors, and PI3-K/Akt in vascular smooth muscle cells.
AB  - In our previous study, bradykinin (BK) exerts its mitogenic effect through
      Ras/Raf/MEK/MAPK pathway in vascular smooth muscle cells (VSMCs). In addition to
      this pathway, the non-receptor tyrosine kinases (Src), EGF receptor (EGFR), and
      phosphatidylinositol 3-kinase (PI3-K) have been implicated in linking a variety
      of G-protein coupled receptors to MAPK cascades. Here, we investigated whether
      these different mechanisms participating in BK-induced activation of p42/p44 MAPK
      and cell proliferation in VSMCs. We initially observed that BK- and EGF-dependent
      activation of Src, EGFR, Akt, and p42/p44 MAPK and [3H]thymidine incorporation
      were mediated by Src and EGFR, because the Src inhibitor PP1 and EGFR kinase
      inhibitor AG1478 abrogated BK- and EGF-dependent effects. Inhibition of PI3-K by
      LY294002 attenuated BK-induced Akt and p42/p44 MAPK phosphorylation and
      [3H]thymidine incorporation, but had no effect on EGFR phosphorylation,
      suggesting that EGFR may be an upstream component of PI3-K/Akt and MAPK in these
      responses. This hypothesis was supported by the tranfection with dominant
      negative plasmids of p85 and Akt which significantly attenuated BK-induced Akt
      and p42/p44 MAPK phosphorylation. Pretreatment with U0126 (a MEK1/2 inhibitor)
      attenuated the p42/p44 MAPK phosphorylation and [3H]thymidine incorporation
      stimulated by BK, but had no effect on Akt activation. Moreover, BK-induced
      transactivation of EGFR and cell proliferation was blocked by matrix
      metalloproteinase inhibitor GM6001. These results suggest that, in VSMCs, the
      mechanism of BK-stimulated activation of p42/p44 MAPK and cell proliferation was
      mediated, at least in part, through activation of Src family kinases, EGFR
      transactivation, and PI3-K/Akt.

PMID- 15573402
TI  - Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal
      cell death?
AB  - Experimental traumatic brain injury (TBI) and spinal cord injury (SCI) result in
      a rapid and significant necrosis of neuronal tissue at the site of injury. In the
      ensuing hours and days, secondary injury exacerbates the primary damage,
      resulting in significant neurologic dysfunction. It is believed that alterations
      in excitatory amino acids (EAA), increased reactive oxygen species (ROS), and the
      disruption of Ca(2+) homeostasis are major factors contributing to the ensuing
      neuropathology. Mitochondria serve as the powerhouse of the cell by maintaining
      ratios of ATP:ADP that thermodynamically favor the hydrolysis of ATP to ADP +
      P(i), yet a byproduct of this process is the generation of ROS. Proton-pumping by
      components of the electron transport system (ETS) generates a membrane potential
      (DeltaPsi) that can then be used to phosphorylate ADP or sequester Ca(2+) out of
      the cytosol into the mitochondrial matrix. This allows mitochondria to act as
      cellular Ca(2+) sinks and to be in phase with changes in cytosolic Ca(2+) levels.
      Under extreme loads of Ca(2+), however, opening of the mitochondrial permeability
      transition pore (mPTP) results in the extrusion of mitochondrial Ca(2+) and other
      high- and low-molecular weight components. This catastrophic event discharges
      DeltaPsi and uncouples the ETS from ATP production. Cyclosporin A (CsA), a potent
      immunosuppressive drug, inhibits mitochondrial permeability transition (mPT) by
      binding to matrix cyclophilin D and blocking its binding to the adenine
      nucleotide translocator. Peripherally administered CsA attenuates mitochondrial
      dysfunction and neuronal damage in an experimental rodent model of TBI, in a dose
      dependent manner. The underlying mechanism of neuroprotection afforded by CsA is
      most likely via interaction with the mPTP because the immunosuppressant FK506,
      which has no effect on the mPT, was not neuroprotective. When CsA was
      administrated after experimental SCI at the same dosage and regimen used TBI
      paradigms, however, it had no beneficial neuroprotective effects. This review
      takes a comprehensive and critical look at the evidence supporting the role for
      mPT in central nervous system (CNS) trauma and highlights the differential
      responses of CNS mitochondria to mPT induction and the implications this has for
      therapeutically targeting the mPT in TBI and SCI.

PMID- 15573403
TI  - Differential response of glutamine in cultured neurons and astrocytes.
AB  - Glutamine, a byproduct of ammonia detoxification, is found elevated in brain in
      hepatic encephalopathy (HE) and other hyperammonemic disorders. Such elevation
      has been implicated in some of the deleterious effects of ammonia on the central
      nervous system (CNS). Recent studies have shown that glutamine results in the
      induction of the mitochondrial permeability transition (MPT) in cultured
      astrocytes. We examined whether glutamine shows similar effects in cultured
      neurons. Both cultured astrocytes and neurons were exposed to glutamine (6.5 mM)
      for 24 hr and the MPT was assessed by changes in cyclosporin A (CsA)-sensitive
      inner mitochondrial membrane potential (DeltaPsi(m)) using the potentiometric dye
      tetramethylrhodamine ethyl ester (TMRE). Glutamine significantly dissipated the
      DeltaPsi(m) in astrocytes as demonstrated by a decrease in mitochondrial TMRE
      fluorescence, a process that was blocked by CsA. On the other hand, treatment of
      cultured neurons with glutamine had no effect on the DeltaPsi(m). Dissipation of
      the DeltaPsi(m) in astrocytes by glutamine was blocked by treatment with 6-diazo
      5-oxo-L-norleucine (DON; 100 microM), suggesting that glutamine hydrolysis and
      the subsequent generation of ammonia, which has been shown previously to induce
      the MPT, might be involved in MPT induction by glutamine. These data indicate
      that astrocytes but not neurons are vulnerable to the toxic effects of glutamine.
      The selective induction of oxidative stress and the MPT by glutamine in
      astrocytes may partially explain the deleterious affects of glutamine on the CNS
      in the setting of hyperammonemia, as well as account for the predominant
      involvement of astrocytes in the pathogenesis of HE and other hyperammonemic
      conditions.

PMID- 15573404
TI  - Downregulation of complexin I and complexin II in the medial thalamus is blocked
      by N-acetylcysteine in experimental Wernicke's encephalopathy.
AB  - Metabolic dysfunction as a consequence of thiamine (vitamin B1) deficiency (TD),
      a model of Wernicke's encephalopathy, leads to elevation of extracellular
      glutamate concentration in vulnerable brain regions consistent with the
      development of excitotoxicity. Complexin I and complexin II are two genes
      labeling principally inhibitory and excitatory synapses, respectively. Because
      current evidence supports an important role for complexins in the modulation of
      neurotransmitter release, we examined the involvement of both proteins in the
      pathology of the medial thalamus and inferior colliculus in TD rats by
      immunoblotting. At the symptomatic stage, complexin I and complexin II levels in
      the medial thalamus were decreased by 63% and 45%, respectively, compared to
      control animals, but were unchanged in the inferior colliculus. These changes in
      thalamus were also observed using immunohistochemical methods, and seemed to be
      due to downregulation of both proteins because synaptophysin levels were
      unaffected in this brain region. In addition, cotreatment with the antioxidant N-
      acetylcysteine prevented both neuronal loss and downregulation of complexins. Our
      findings suggest dysregulation of excitatory and inhibitory neurotransmitter
      release in the medial thalamus, which is not present in the inferior colliculus.
      Furthermore, loss of complexin I and II in the thalamus may be mediated by
      processes that involve oxidative stress. Such changes in complexin levels may
      contribute to the pathophysiology of thalamic damage in TD, and offer a potential
      basis for the well-known differences in pathology between this structure and the
      inferior colliculus in this disorder.

PMID- 15573405
TI  - Brain lactate synthesis in thiamine deficiency: a re-evaluation using 1H-13C
      nuclear magnetic resonance spectroscopy.
AB  - Region-selective accumulation of brain lactate occurs in TD; however, the
      mechanisms responsible have not been elucidated fully. (1)H and (13)C nuclear
      magnetic resonance (NMR) spectroscopy were therefore used to investigate de novo
      lactate synthesis from [1-(13)C]glucose in vulnerable (medial thalamus) and
      nonvulnerable (frontal cortex) brain regions of rats made thiamine deficient by
      administration of the central thiamine antagonist pyrithiamine. De novo synthesis
      of lactate was increased in the medial thalamus to 148% and 226% of pair-fed
      control values at presymptomatic and symptomatic stages of thiamine deficiency,
      respectively, whereas no such changes were observed in the frontal cortex.
      Administration of a glucose load selectively worsened the changes in medial
      thalamus. Pyruvate recycling and peripherally derived lactate did not contribute
      significantly to the lactate increase within the thiamine-deficient brain.
      Increases in immunolabeling of the lactate dehydrogenase isoenzymes (LDH1 and
      LDH5) were observed in the medial thalamus of thiamine-deficient animals.
      Metabolic impairment due to thiamine deficiency thus results in increased
      glycolysis, increased LDH immunolabeling of neurons and astrocytes and increased
      de novo synthesis of lactate in brain regions vulnerable to thiamine deficiency.
      These results are consistent with the notion that focal lactate accumulation
      participates in the worsening of neurologic symptoms in thiamine-deficient
      patients.

PMID- 15573406
TI  - Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability
      transition.
AB  - Mitochondria are involved directly in cell survival and death. The assumption has
      been made that drugs that protect mitochondrial viability and prevent apoptotic
      cascade-induced mitochondrial permeability transition pore (MPTp) opening will be
      cytoprotective. Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent
      irreversible monoamine oxidase (MAO) B inhibitor anti-Parkinson drug. Unlike
      selegiline, it is not derived from amphetamine, and is not metabolized to
      neurotoxic L-methamphetamine derivative. In addition, it does not have
      sympathomimetic activity. Rasagiline is effective as monotherapy or adjunct to
      levodopa for patients with early and late Parkinson's disease (PD) and adverse
      events do not occur with greater frequency in subjects receiving rasagiline than
      in those on placebo. Phase III controlled studies indicate that it might have a
      disease-modifying effect in PD that may be related to its neuroprotective
      activity. Its S isomer, TVP1022, is more than 1,000 times less potent as an MAO
      inhibitor. Both drugs, however, have neuroprotective activity in neuronal cell
      cultures in response to various neurotoxins, and in vivo in response to global
      ischemia, neurotrauma, head injury, anoxia, etc., indicating that MAO inhibition
      is not a prerequisite for neuroprotection. Their neuroprotective effect has been
      demonstrated to be associated directly with the propargylamine moiety, which
      protects mitochondrial viability and MTPp by activating Bcl-2 and protein kinase
      C (PKC) and by downregulating the proapoptotic FAS and Bax protein families.
      Rasagiline and its derivatives also process amyloid precursor protein (APP) to
      the neuroprotective, neurotrophic, soluble APP alpha (sAPPalpha) by PKC- and MAP
      kinase-dependent activation of alpha-secretase. The identification of the
      propargylamine moiety as the neuroprotective component of rasagiline has led us
      to development of novel bifunctional anti-Alzheimer drugs (ladostigil) possessing
      cholinesterase and brain-selective MAO inhibitory activity and a similar
      neuroprotective mechanism of action.

PMID- 15573407
TI  - In vitro interaction between silicone gel and human monocyte-macrophages.
AB  - Controversy remains regarding the ability of silicone materials to induce a
      specific immune reaction versus a nonspecific inflammatory response.
      Histopathological analysis of the tissue around failed breast implants reveals
      chronic inflammation with silicone gel droplets either surrounded by giant cells
      or engulfed by macrophages, areas of fibrosis, and necrosis. Macrophages are the
      key cells engulfing or forming foreign body giant cells. To address the
      mechanisms of silicone-induced inflammation a model of human monocyte-derived
      macrophages (MDMs) was developed. After sonication of silicone gel, the silicone
      droplets were embedded in Type I collagen and used to coat glass coverslips;
      human MDMs were subsequently seeded on the coverslips and maintained in culture
      for up to 7 days. The advantage of the model was that human macrophages could be
      studied histologically, and cytochemically as they interacted with well
      characterized silicone materials. Initial analysis of the human macrophages shows
      phagocytosis of the silicone gel within hours of exposure to the material.
      Analysis for pro-inflammatory cytokines reveals significant transient secretion
      of IL-1 (p < 0.01) over controls by human macrophages upon exposure to silicone
      gel at 24 h.

PMID- 15573408
TI  - Lactate utilization by brain cells and its role in CNS development.
AB  - We studied the role played by lactate as an important substrate for the brain
      during the perinatal period. Under these circumstances, lactate is the main
      substrate for brain development and is used as a source of energy and carbon
      skeletons. In fact, lactate is used actively by brain cells in culture. Neurons,
      astrocytes, and oligodendrocytes use lactate as a preferential substrate for both
      energy purposes and as precursor of lipids. Astrocytes use lactate and other
      metabolic substrates for the synthesis of oleic acid, a new neurotrophic factor.
      Oligodendrocytes mainly use lactate as precursor of lipids, presumably those used
      to synthesize myelin. Neurons use lactate as a source of energy and as precursor
      of lipids. During the perinatal period, neurons may use blood lactate directly to
      meet the need for the energy and carbon skeletons required for proliferation and
      differentiation. During adult life, however, the lactate used by neurons may come
      from astrocytes, in which lactate is the final product of glycogen breakdown. It
      may be concluded that lactate plays an important role in brain development.

PMID- 15573409
TI  - Molecular and cellular mechanisms of neuroprotection by vascular endothelial
      growth factor.
AB  - The present view of the neuroprotective functions and mechanisms of action of
      vascular endothelial growth factor (VEGF) is based on studies of neuronal
      ischemic/hypoxic models in vivo and in vitro. Endogenous neuronal VEGF increases
      in the ischemic brain and plays a neuroprotective role in the pathophysiologic
      processes that follow stroke. Exogenous VEGF, directly administered or
      overexpressed by gene delivery into rat brains, reduces ischemic brain infarct
      and decreases hypoxic neuronal death. The main neuroprotective mechanisms of VEGF
      include: (1) modulation of the phosphatidylinositol 3'-kinase (PI3K)/Akt/nuclear
      factor-kappaB signaling pathway, inhibition of caspase-3 activity, and reduction
      of ischemic neuronal apoptosis; (2) inhibition of outward delayed rectifier
      potassium channel currents and increase of ischemia-induced tyrosine
      phosphorylation of Kv1.2 potassium channel proteins via activation of the PI3K
      pathway; and (3) enhancement of proliferation and migration of neural progenitors
      in the subventricular zone and improvement of striatal neurogenesis and
      maturation of newborn neurons in adult rat brains after stroke.

PMID- 15573410
TI  - Peroxide detoxification by brain cells.
AB  - Peroxides are generated continuously in cells that consume oxygen. Among the
      different peroxides, hydrogen peroxide is the molecule that is formed in highest
      quantities. In addition, organic hydroperoxides are synthesized as products of
      cellular metabolism. Generation and disposal of peroxides is a very important
      process in the human brain, because cells of this organ consume 20% of the oxygen
      used by the body. To prevent cellular accumulation of peroxides and damage
      generated by peroxide-derived radicals, brain cells contain efficient
      antioxidative defense mechanisms that dispose of peroxides and protect against
      oxidative damage. Cultured brain cells have been used frequently to investigate
      peroxide metabolism of neural cells. Efficient disposal of exogenous hydrogen
      peroxide was found for cultured astrocytes, oligodendrocytes, microglial cells,
      and neurons. Comparison of specific peroxide clearance rates revealed that
      cultured oligodendrocytes dispose of the peroxide quicker than the other neural
      cell cultures. Both catalase and the glutathione system contribute to the
      clearance of hydrogen peroxide by brain cells. For efficient glutathione
      dependent reduction of peroxides, neural cells contain glutathione in high
      concentration and have substantial activity of glutathione peroxidase,
      glutathione reductase, and enzymes that supply the NADPH required for the
      glutathione reductase reaction. This article gives an overview on the mechanisms
      involved in peroxide detoxification in brain cells and on the capacity of the
      different types of neural cells to dispose of peroxides.

PMID- 15573411
TI  - Inhibition of mitochondrial respiration by nitric oxide: its role in glucose
      metabolism and neuroprotection.
AB  - There is an increasing body of evidence demonstrating that inhibition of
      cytochrome c oxidase by nitric oxide (NO) may be one more step in a signaling
      cascade involved in the physiologic regulation of cell functions. For example, in
      both astrocytes and neurons the inhibition of mitochondrial respiration by
      endogenously produced NO induces transient and modest decreases in cellular ATP
      concentrations. This mitochondrial impairment may serve as a cellular sensor of
      energy charges, hence modulating metabolic pathways, such as glycolysis, through
      AMP-activated protein kinase (AMPK) in astrocytes. In neurons, the NO derivative
      peroxynitrite anion triggers signaling pathways leading to glucose oxidation
      through the pentose-phosphate pathway to form reducing equivalents in the form of
      NADPH. The modulation of these metabolic pathways by nitric oxide or its
      derivatives may be important for understanding the mechanisms by which this free
      radical affects neuronal death or survival.

PMID- 15573412
TI  - Acute inactivation of MAP1b in growing sympathetic neurons destabilizes axonal
      microtubules.
AB  - Microtubule-associated-protein 1b (MAP1b) is abundant in neurons actively
      extending axons. MAP1b is present on microtubules throughout growing axons, but
      is preferentially concentrated on microtubule polymer in the distal axon and
      growth cone. Although MAP1b has been implicated in axon growth and pathfinding,
      its specific functions are not well understood. Biochemical and transfection
      studies suggest that MAP1b has microtubule-stabilizing activity, but recent
      studies with neurons genetically deficient in MAP1b have not confirmed this. We
      have explored MAP1b functions in growing sympathetic neurons using an acute
      inactivation approach. Neurons without axons were injected with polyclonal MAP1b
      antibodies and then stimulated to extend axons. Injected cells were compared to
      controls in terms of axon growth behavior and several properties of axonal
      microtubules. The injected antibodies rapidly and quantitatively sequestered
      MAP1b in the cell body, making it unavailable to perform its normal functions.
      This immunodepletion of MAP1b had no statistically significant effect on axon
      growth, the amount of microtubule polymer in the axon, and the relative
      tyrosinated tubulin content of this polymer, and this was true in sympathetic
      neurons from rat, wild type mice, and tau knockout mice. Thus, robust axon growth
      can occur in the absence of MAP1b alone or both MAP1b and tau. However,
      immunodepletion of MAP1b significantly increased the sensitivity of microtubules
      in the distal axon and growth cone to nocodazole-induced depolymerization. These
      results indicate that MAP1b has microtubule-stabilizing activity in growing
      axons. This stabilizing activity may be required for some axonal functions, but
      it is not necessary for axon growth.

PMID- 15573413
TI  - An age-adjusted bootstrap-based Poly-k test.
AB  - The assumption of an asymptotic normal distribution of some test statistics may
      be invalid in certain dose-response trend tests. For instance, the survival
      adjusted Cochran-Armitage test, known as the Poly-k test, is asymptotically
      standard normal under the null hypothesis. However, the asymptotic normality is
      not valid if there is a deviation from the tumour onset distribution that is
      assumed in this test or if the competing risks survival rates differ across
      groups. We develop an age-adjusted bootstrap-based method to assess the
      significance of assumed asymptotic normal tests for animal carcinogenicity data.
      The proposed method differs from conventional bootstrap methods in the aspect of
      preserving the mortality rate in each dose group under the null hypothesis of
      equal tumour incidence rates among the groups. We investigate an empirical
      distribution of the Poly-3 (P3) trend test statistic using the proposed age
      adjusted bootstrap-based method and compare it with the P3 test statistic
      referenced to the assumed standard normal distribution. A simulation study is
      conducted to evaluate the robustness of these tests to various Weibull-family
      tumour onset distributions. The proposed method is applied to National Toxicology
      Program data sets to evaluate a dose-related trend of a test substance on the
      incidence of neoplasms.

PMID- 15573414
TI  - Effects of substrate stiffness on cell morphology, cytoskeletal structure, and
      adhesion.
AB  - The morphology and cytoskeletal structure of fibroblasts, endothelial cells, and
      neutrophils are documented for cells cultured on surfaces with stiffness ranging
      from 2 to 55,000 Pa that have been laminated with fibronectin or collagen as
      adhesive ligand. When grown in sparse culture with no cell-cell contacts,
      fibroblasts and endothelial cells show an abrupt change in spread area that
      occurs at a stiffness range around 3,000 Pa. No actin stress fibers are seen in
      fibroblasts on soft surfaces, and the appearance of stress fibers is abrupt and
      complete at a stiffness range coincident with that at which they spread.
      Upregulation of alpha5 integrin also occurs in the same stiffness range, but
      exogenous expression of alpha5 integrin is not sufficient to cause cell spreading
      on soft surfaces. Neutrophils, in contrast, show no dependence of either resting
      shape or ability to spread after activation when cultured on surfaces as soft as
      2 Pa compared to glass. The shape and cytoskeletal differences evident in single
      cells on soft compared to hard substrates are eliminated when fibroblasts or
      endothelial cells make cell-cell contact. These results support the hypothesis
      that mechanical factors impact different cell types in fundamentally different
      ways, and can trigger specific changes similar to those stimulated by soluble
      ligands.

PMID- 15573415
TI  - Computer simulation of flagellar movement IX. Oscillation and symmetry breaking
      in a model for short flagella and nodal cilia.
AB  - A computer model of flagella in which oscillation results from regulation of
      active sliding force by sliding velocity can simulate the movements of very short
      flagella and cilia. Of particular interest are the movements of the short (2-3
      microm) nodal cilia of the mammalian embryo, which determine the development of
      the asymmetry of the internal organs. These cilia must generate a
      counterclockwise (viewed from base to tip) circling motion. A three-dimensional
      computer model, with active force generated by a simple mathematical formulation
      and regulated by sliding velocity, can generate this circling motion if a time
      delay process is included in the control specification. Without the introduction
      of a symmetry-breaking mechanism, the computer models start randomly in either
      direction, and maintain either clockwise or counterclockwise circling. Symmetry
      can be broken by at least two mechanisms: (1) control of dynein activity on one
      outer doublet by sliding velocity can be influenced by the sliding velocity
      experienced on an adjacent outer doublet, or (2) a constant twist of the axoneme
      caused by an off-axis component of dynein force. This second mechanism appears
      more reasonable, but its effectiveness is highly dependent upon specifications
      for the elastic resistances of the model. These symmetry-breaking mechanisms need
      to be present only at the beginning of circling. With these models, once a
      circling direction is established, it remains stable even if the symmetry
      breaking mechanism is removed.

PMID- 15573416
TI  - Average peptide score: a useful parameter for identification of proteins derived
      from database searches of liquid chromatography/tandem mass spectrometry data.
AB  - The quantity and variable quality of data that can be generated from liquid
      chromatography (LC)/mass spectrometry (MS)-based proteomics analyses creates many
      challenges in interpreting the spectra in terms of the actual proteins in a
      complex sample. In spite of improvements in algorithms that match putative
      peptide sequences to MS/MS spectra, the assembly of these lists of possible or
      probable peptides into a 'correct' set of proteins is still problematic. We have
      observed a trend in a simple relationship, derived from standard database search
      outputs, which can be useful in assessing the quality of a MS/MS-based protein
      identification. Specifically, the ratio of the protein score and number of non
      redundant peptides, or average peptide score (APS), can facilitate initial
      filtering of database search results in addition to providing a useful measure of
      confidence for the proteins identified. This parameter has been applied to
      results from the analysis of multi-protein complexes derived from pull-down
      experiments analyzed using a two-dimensional LC/MS/MS workflow. In particular,
      the complex list of protein identifications derived from a drug affinity pull
      down with immobilized ampicillin and an E. coli lysate was greatly simplified by
      applying the APS as a filter, allowing for facile identification of the
      penicillin-binding proteins known to interact with ampicillin. Furthermore, an
      APS threshold can be used for any data sets derived from electrospray ionization
      (ESI)- or matrix-assisted laser desorption/ionization (MALDI)-MS/MS experiments
      and is also not specific to any database search program.

PMID- 15573417
TI  - Evaluation of a hydrogen laser vacuum ultraviolet source for photoionization mass
      spectrometry of pharmaceuticals.
AB  - A photoionization hydrogen laser time-of-flight mass spectrometer system (H2
      TOFMS) has been evaluated for the rapid analysis of drugs of abuse and
      pharmaceutical agents extracted from prescription tablets and spiked urine
      samples. The spectra obtained using the H2-TOFMS showed primarily intact
      molecular ions (M+*) after introduction by a heated probe and irradiation with
      vacuum ultraviolet (VUV) photons from the laser. Samples analyzed by this
      technique required only a simple solid-phase extraction step; no chromatographic
      separation or derivatization was necessary to identify the drugs of abuse or
      pharmaceutical agents.

PMID- 15573418
TI  - Force protection: today's reality.
AB  - Most US infrastructure and major chemical manufacturing facilities as well as
      their supporting utility systems are inherently vulnerable to a terrorist attack.
      Force protection is a military and civilian term used to protect personnel and
      critical facilities and assets against would-be aggressors or terrorists. The war
      on terrorism is a 200-300-year war. Terrorist attacks on US soil could become as
      common-place as in the State of Israel. It is very easy to penetrate
      infrastructure or plants as evidenced by vulnerability assessments performed for
      states, cities, plants, and military facilities by Versar and others around the
      country. Chemical, biological, radiological, nuclear, and explosive weapons can
      be readily used to attack facilities in the US. This paper will explain some of
      those vulnerabilities, outline the current DoD standard as it relates to
      vulnerability assessments, and explain how this may be used in commercial
      applications to deter potential aggressors.

PMID- 15573419
TI  - Altered nuclear factor kappa-B activity and mercury-induced kidney tubule cell
      apoptosis: implications for renal failure.

PMID- 15573420
TI  - Observations on abortion and politics.

PMID- 15573421
TI  - Transhumanism: toward a brave new world?

PMID- 15573422
TI  - Milestones in Jewish medical ethics: medical-halachic literature in Israel, 1948
      1998.

PMID- 15573423
TI  - Development of the NHPCO research agenda.
AB  - In April 2003, a group of 35 leading researchers in hospice and palliative care
      participated in a research conclave to promote collaboration in our emerging
      field through a review of the current research priorities. The conclave was
      organized to pursue the following objectives: 1) to improve communication among
      existing centers of research excellence, 2) to explore opportunities for creating
      practice-based research networks, and 3)to identify critical areas of need for
      investigation. The conclave highlighted numerous areas of unexplored research and
      identified important issues in the field. Based on the input from participants in
      the conclave, and from other constituencies, NHPCO has developed are search
      agenda with the goal of framing important research objectives and questions
      that,if answered, would make an important contribution to our field. This report
      summarizes key issues identified by participants in the research conclave and
      presents the NHPCOresearch agenda, which is designed to further our goal of
      improving access to quality hospice and palliative care for patients who are at
      the end of life.

PMID- 15573424
TI  - Who decides--the patient, the physician or the rabbi?

PMID- 15573425
TI  - Halacha and psychological treatment dilemmas and conflicts.
AB  - Two of the many issues that present halachic-treatment problems for the orthodox
      mental-health practitioner are the issues of honoring parents and treatment
      practices, and confidentiality and religious obligations. The clinical-religious
      aspects of the above are analyzed and discussed, via correspondence, by a
      psychotherapist and a respected halachic scholar.

PMID- 15573426
TI  - The use of embryonic stem cells for therapeutic research (the August 2001
      report).

PMID- 15573427
TI  - Regulation of research on the decisionally impaired: history and gaps in the
      current regulatory system.

PMID- 15573428
TI  - Issues raised by research using persons suffering from dementia who have impaired
      decisional capacity.

PMID- 15573429
TI  - In harm's way: research subjects who are decisionally impaired.

PMID- 15573430
TI  - Assessment of capacity to give consent to research participation: state-of-the
      art and beyond.

PMID- 15573431
TI  - Protecting vulnerable research subjects: practical realities of institutional
      review board review and approval.

PMID- 15573432
TI  - Should hypotheses concerning species status be considered alongside other
      hypotheses in genetic studies of species complexes? A response to Van Bortel and
      Coosemans 2003.

PMID- 15573433
TI  - The National Bioethics Advisory Commission: bridging the gaps in human subjects
      research protection.

PMID- 15573434
TI  - Proxy consent to participation of the decisionally impaired in medical resesarch-
      Maryland's policy initiative.

PMID- 15573435
TI  - Regulating research with vulnerable populations: litigation gone awry.

PMID- 15573436
TI  - Achieving proper balance in research with decisionally-incapacitated subjects:
      NAMI's perspectives on the working group's proposal.

PMID- 15573437
TI  - Comments on the Second Report of the Maryland Attorney General's Research Working
      Group.

PMID- 15573438
TI  - An act concerning research--protection of decisionally incapacitated individuals
      (Draft, May 5, 1997 Part I).

PMID- 15573439
TI  - An act concerning health care decisions--surrogate decision makers (Draft, May 5,
      1997 Part II).

PMID- 15573440
TI  - An act concerning consent to research--protection of decisionally incapacitated
      individuals (Draft, August 1, 1997).

PMID- 15573441
TI  - Bioethical malpractice: risk and responsibilities in human research.

PMID- 15573442
TI  - AIDS and adolescents.

PMID- 15573443
TI  - The human face of Alzheimer's.

PMID- 15573444
TI  - Stem cells and the Reagan legacy.

PMID- 15573445
TI  - Our asterisked heroes.

PMID- 15573446
TI  - Guilt by association: should the law be able to use one person's DNA to carry out
      surveillance on their family? Not without a public debate.

PMID- 15573447
TI  - IVF seems safe but only time will tell.

PMID- 15573448
TI  - Fetal tissue graft restores lost sight.

PMID- 15573449
TI  - Truth-telling and comfort.

PMID- 15573450
TI  - Choosing life when life is not a choice.

PMID- 15573451
TI  - Choose life--I really mean it!

PMID- 15573452
TI  - [From granuloma to granulomatosis].

PMID- 15573453
TI  - Dietary intake in the diabetes prevention program cohort: baseline and 1-year
      post randomization.
AB  - PURPOSE: To describe usual dietary intake assessment at baseline and 1-year post
      randomization in the ethnically diverse Diabetes Prevention Program cohort.
      METHODS: Participants were randomized to Lifestyle Modification, Metformin, or
      Placebo. Usual diet was assessed by a modified, previously validated food
      frequency interview. RESULTS: Complete data were available for 2934 subjects
      (90.7% of those randomized). Baseline median estimated energy intake was 7676
      kJ/d (1828 kcal/d) and 8585 kJ/d (2044 kcal/d) for women and men, respectively.
      The median percent of energy from fat ranged from 30.6% for Asian American men to
      37.5% for American Indian men and women. After 1 year among the Lifestyle group,
      the median change in total energy and percent energy from fat was -1897 kJ/d (
      452 kcal/d) and -6.6%, respectively. For the Metformin and Placebo groups, change
      in median total energy was -1235 kJ/d (-294 kcal/d) and-1051 kJ/d (-250 kcal/d),
      respectively, and change in median percent energy from fat was -0.8% and-0.8%,
      respectively (p < 0.001 for differences between groups, adjusted for gender and
      ethnicity). CONCLUSIONS: One-year post-randomization, significant differences in
      dietary intake were observed in the Lifestyle compared with the Metformin or
      Placebo group, and these were consistent with the general intent of the DPP
      lifestyle modification intervention.

PMID- 15573454
TI  - Identification of the putative collagen X gene from the pufferfish Fugu rubripes.
AB  - The type X collagen gene is the classical marker of hypertrophic chondrocytes.
      Mutations in the human collagen X gene cause metaphyseal chondrodysplasia type
      Schmid (MCDS). In order to gain insight into the evolution of collagen X genes,
      we identified a putative collagen X gene from the pufferfish Fugu rubripes. We
      demonstrated expression of the putative Fugu collagen X gene by reverse
      transcription-polymerase chain reaction (RT-PCR) with primers spanning intron 1.
      The Fugu collagen X gene shares a common gene structure and high amino acid
      identity with mammalian and chicken collagen X genes. Interestingly, we have
      found that most of the residues mutated in human MCDS are highly conserved in the
      Fugu gene. The availability of the Fugu collagen X gene sequence will be of value
      in the identification of functionally important residues within the protein and
      for delineating regulatory elements that control collagen X gene expression in
      chondrocytes.

PMID- 15573457
TI  - Bibliography of Toxinology.

PMID- 15573458
TI  - Axonal transport hypothesis moves on to implicate presenilin: Alzheimer research
      forum live discussion.

PMID- 15573459
TI  - The greatest reward.

PMID- 15573460
TI  - Access to care in a changing profession.

PMID- 15573461
TI  - Pediatric dentistry.

PMID- 15573462
TI  - Contemporary pediatric restorative dentistry.

PMID- 15573463
TI  - Pediatric sedation: current teachings vs. private practice reality.

PMID- 15573464
TI  - Use of presurgical nasal alveolar molding appliance in treating cleft lip and
      palate patients.

PMID- 15573465
TI  - Child residents of Texas: the next generation of dental patients.

PMID- 15573466
TI  - Ethical dilemma #49. "Extreme makeover: we want her to be a winner".

PMID- 15573467
TI  - Oral and maxillofacial pathology case of the month. Sialolithiasis.

PMID- 15573468
TI  - Safety pharmacology of DW-224a, a novel fluoroquinolone antibiotic agent.
AB  - To investigate the safety pharmacology of a novel fluoroquinolone antibiotic
      agent, DW-224a, on the vital functions, we studied its effects on the central
      nervous system, cardiovascular system and respiratory system. To determine the
      effects on the central nervous system, we used a modified Irwin's test at each
      time point after oral administration of DW-224a to mice. In this test, we found
      that the treatment of test article had no effects on motor activity, behavioral
      changes, coordination, and sensory/motor reflex responses. The effects of DW-224a
      on the cardiovascular system were evaluated by the use of a telemetry system in
      beagle dogs. At 360 min post-DW-224a (100 mg/kg) administration, QT interval
      prolongation was observed. However, there were no changes in heart rate, blood
      pressure, and electrocardiogram at all doses and each time points with the
      exception of QT-interval prolongation as compared to the vehicle treated group.
      In experiments designed to determine the changes of respiratory function in rats,
      we found no changes at all doses and time points. We investigated the effects of
      DW-224a on the human ether-a-go-go-related gene (hERG) mediated potassium
      currents to evaluate its potential to induce QT interval prolongation. When whole
      cell patch-clamp electrophysiology was used, DW-224a inhibited hERG currents with
      IC50 of 218.12 +/- 39.51 microM though its effect was less potent than that of E
      4031, a positive control drug. Our data suggested that DW-224a showed no adverse
      effects on the central nervous system, cardiovascular system, and respiratory
      system, with the exception of the effect on the QT interval prolongation.

PMID- 15573469
TI  - The toxicity profile of hydrolyzed aqueous olive pulp extract.
AB  - The toxicity profile of HIDROX (Hydrolyzed Aqueous Olive Pulp Extract; OPE) was
      characterized in a series of toxicology studies. A limit dosage of 2000 mg/kg
      produced no toxicity in mice (acute oral NOAEL: 2000 mg/kg). In rats, an acute
      oral NOAEL of 2000 mg/kg was established, based on reductions in weight gains in
      both sexes at 5000 mg/kg. Reduced gains in female rats at 1500 and 2000 mg/kg
      were not significantly different from control values. Daily oral dosages of 1000,
      1500 and 2000 mg/kg/day for 90 days produced small decreases in body weight gains
      at 2000 mg/kg/day in the male rats and in all groups of female rats. Feed
      consumption was comparable to controls. There were no adverse clinical,
      hematologic, biochemical, organ weight or gross necropsy effects. Focal, minimal
      or mild hyperplasia of the mucosal squamous epithelium of the limiting ridge of
      the forestomach occurred in some rats at 2000 mg/kg/day; this change was
      attributed to local irritation by repeated intubation of large volumes of
      viscous, granular dosing suspension. A NOAEL of 2000 mg/kg/day was established
      for the 90-day study, based on the lack of significant adverse effects.
      Toxicokinetic data indicated that hydroxytyrosol (HT, the major component of OPE)
      was rapidly absorbed. Mean concentrations were measurable through 1 to 4 hours
      (t(last)) at 1000 and 1500 mg/kg/day and through 8 hours at 2000 mg/kg/day.
      Dosages of OPE ranging from 500 to 2000 mg/kg/day did not adversely affect any of
      the mating, fertility, delivery or litter parameters investigated in an oral rat
      dosage-range reproduction study. Adverse effects were also absent in a rat
      developmental toxicity study in which pregnant dams were treated with 1000, 1500
      or 2000 mg/kg/day on days 6 through 20 of gestation. Plasma levels for pregnant
      and lactating rats were comparable to non-pregnant rats; minimal levels crossed
      the placenta. Quantifiable levels were not identified in maternal milk or plasma
      from nursing pups. A bacterial reverse mutation and a CHO chromosome aberration
      assay revealed evidence of mutagenic activity at high dosages with S9 metabolic
      activation. However, three rat micronucleus evaluations performed after single
      and repeated (28-day) dosages of up to 2000 mg/kg/day and dosages of 5000
      mg/kg/day for 29 days resulted in negative findings; therefore, OPE was not
      considered to be mutagenic in this in vivo assay.

PMID- 15573470
TI  - Methyl phenyl selenide causes heme biosynthesis impairment and its toxicity is
      not modified by dimethyl sulphoxide in vivo.
AB  - Organoselenium compounds can cause anemia in mice, possibly as a consequence of
      impairment of the heme biosynthesis pathway. Such compounds can inhibit the
      sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (delta-ALA-D),
      which is involved in the heme biosynthetic pathway, leading to a decrease in the
      syntheses of hemoglobin, cytochromes and other heme-proteins. Methyl phenyl
      selenide (CH3SePh) has chemopreventive activity against cancer in rodents,
      raising the possibility of therapeutic use of this compound by humans. Treatment
      with methyl phenyl selenide (500 micromol/kg/day, 30 days) inhibited the delta
      aminolevulinate dehydratase activity in adult male mice. Furthermore, the
      exposure to methyl phenyl selenide caused an increase in the liver/body weight
      ratio and a decrease in the hemoglobin content when compared to the control
      animals. The vehicle used (DMSO or corn oil) did not affect any of the analyzed
      parameters or the selenide effects towards these parameters. In summary, results
      presented here support that delta-aminolevulinate dehydratase is a potential
      target to CH3SePh, leading to an impairment of hemoglobin content, a heme
      biosynthetic endpoint.

PMID- 15573471
TI  - Binding of perfluorooctanoic acid to rat liver-form and kidney-form alpha2u
      globulins.
AB  - Perfluorooctanoic acid (PFOA) is an organic fluorochemical and is reported to
      have a long half-life in human blood. Its urinary elimination in rats is markedly
      sex-dependent, and characterized by significantly longer plasma half-life of PFOA
      in male rats than in females. It has been postulated that male-specific PFOA
      binding protein(s) is responsible for the long half-life of PFOA in male rats. In
      this paper, two male rat specific proteins, liver- and kidney-form alpha2u
      globulins (A2U(L) and A2U(K)), were purified from male rat urine and kidney,
      respectively. The binding of these two nroteins to PFOA was investigated using
      ligand blotting, electrospray ionization mass spectrometry and fluorescence
      competitive binding assay. The results revealed that both A2U(L) and A2U(K) were
      able to bind PFOA in vitro under physiological conditions, and that PFOA and a
      fluorescent-labeled fatty acid shared the same binding site on both A2U(L) and
      A2U(K). The binding affinities, however, are relatively weak. The estimated
      dissociation constants are in the 10(-3) M range, indicating that bindings of
      PFOA to either A2U(L) or A2U(K) cannot adequately explain the sex-dependent
      elimination of PFOA in rats, and it is unlikely that PFOA-A2U(K) binding would
      induce A2U nephropathy as seen with, for example, 1,4-dichlorobenzene.

PMID- 15573472
TI  - 13-week dietary toxicity study of ammonium perfluorooctanoate (APFO) in male
      rats.
AB  - Ammonium perfluorooctanoate is a perfluorinated carboxylate that is used
      commercially as a processing aid in the production of fluorinated polymers.
      Perfluorooctanoate (PFOA) has been found in human blood of the general population
      from exogenous sources. This report presents the results of a 13-week dietary
      toxicity study in male rats and was designed to identify potential target
      organ(s), dose response, and to explore possible relationships of PPARalpha
      activation to potential liver effects and hormonal changes. Rats were fed dietary
      levels of 0, 1, 10, 30, and 100 ppm (equivalent to 0, 0.06, 0.64, 1.94, and 6.5
      mg/kg/day) for 13 weeks. A control group pair-fed adjusted to the 100 ppm level
      and groups allowed to recover for 8 weeks were included. Sacrifices were
      conducted after 4, 7, and 13 weeks of feeding and after 8 weeks of recovery. At
      each sacrifice, gross and histopathology was conducted on selected tissues and
      measurements of hepatic palmitoyl CoA oxidase (PCoAO), as well as serum
      estradiol, luteinizing hormone, testosterone, and PFOA were determined. There
      were no clinical signs or mortality. Body weight gains were reduced in the 100
      ppm dose group. Liver weights (absolute and relative), PCoAO activity, and
      hepatocyte hypertrophy (minimal to mild) were increased in the 10 ppm dose group
      and above and were reversible in recovery. Under the study conditions, hormone
      levels appeared unchanged. PFOA serum concentrations increased in a dose-related
      fashion, appeared to reach steady-state by test week 5, and declined rapidly
      through the recovery period. Serum PFOA concentrations at the end of the
      treatment period were 7.1, 41, 70, and 138 microg/mL in the 1, 10, 30 and 100 ppm
      dose groups. The study no effect level was 1 ppm (0.06 microg/mg) with doses of
      10 ppm (0.64 microg/mg) and higher producing adaptive and reversible liver
      changes.

PMID- 15573473
TI  - Olanzapine induced thrombocythemia in Sprague-Dawley rats.
AB  - Olanzapine was administered orally (20 mg/kg/day) in Sprague-Dawley rats. Forty
      eight male Sprague-Dawley rats were divided into eight groups of six animals
      each. Four groups of animals received olanzapine for 7, 14, 21 and 48 days. There
      were no significant changes in hematological, clinical biochemistry parameters
      and superoxide dismutase activity in pancreas, liver and brain of all the groups.
      No significant changes in malonaldehyde levels were observed in liver and brain
      of all the groups. A significant increase in malonaldehyde levels in pancreas
      were observed in all the treatment groups; however, no increase in serum glucose
      levels were seen in these animals. A significant increase in platelet numbers in
      the treatment groups poses a serious threat regarding long-term use of
      olanzapine.

PMID- 15573474
TI  - Effect of dexamethasone treatment on oxidative energy metabolism in rat liver
      mitochondria during postnatal developmental periods.
AB  - Dexamethasone--a potent synthetic glucocorticoid--has multiple therapeutic
      applications and is used in all age groups, as well as for antenatal and
      perinatal treatments. However, side-effects of dexamethasone treatment, including
      those on development, are becoming increasingly apparent. Since developmental
      processes are energy-dependent, we examined the effects of chronic dexamethasone
      treatment on oxidative energy metabolism in liver mitochondria from rats
      belonging to different developmental age groups. Dexamethasone treatment
      adversely affected the state 3 respiration rates in 2- and 3-week groups and in
      the adults with glutamate as the substrates, whereas for pyruvate + malate, the
      adverse effects were seen for the 3 week and the adult groups. Oxidation of
      succinate was severely impaired in all the age groups. For ascorbate + TMPD as
      the substrate, elevated respiration was noted for the 5-week group and the
      impaired oxidation was observed in adults. Dexamethasone treatment also resulted
      in site-specific uncoupling with the effect being seen predominantly in the 3-
      and 5-week and adult animals. The activity of dehydrogenases decreased in a
      manner comparable to the respiration rates. The mitochondrial cytochromes
      decreased in an age-dependent manner. The ATPase activity also decreased
      significantly. The results thus emphasize the adverse effects of dexamethasone
      treatment on mitochondrial energy metabolism especially in critical age groups.

PMID- 15573475
TI  - The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption
      and cognitive function: a review.
AB  - Thyroid hormones (TH) are essential to normal brain development, influencing
      behavior and cognitive function in both adult and children. It is suggested that
      conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and
      generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral
      impulses found in cases of attention deficit hyperactivity disorder (ADHD) and
      other cognitive disorders. Disrupters of TH are various and prevalent in the
      environment. This paper reviews the mechanisms of TH disruption caused by the
      general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid
      disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis,
      as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH
      induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in
      accelerated clearance of TH. PHAHs can compromise function of transport and
      receptor binding proteins such as transthyretin and aryl hydrocarbon receptors
      (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain
      by the presence of PHAH. Further, PHAH can alter brain growth and development by
      perturbing cytoskeletal formation, thereby affecting neuronal migration,
      elongation and branching. The complex relationships between PHAH and cognitive
      function are examined in regard to the disruption of T4 regulation in the
      hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and
      postnatal development.

PMID- 15573476
TI  - Toluene and p-xylene induced LLC-PK1 apoptosis.
AB  - Occupational exposure to organic solvents was found to be associated with
      development and progression of tubulo-interstitial fibrosis and chronic renal
      failure. However, the cellular mechanism by which this occurs remains elusive.
      This study was conducted to evaluate the mode of cell death in proximal tubular
      cells exposed to organic solvents. LLC-PK1 cell line cytotoxicity due to exposure
      to 1 mM of either p-xylene or toluene was compared to untreated control by cell
      viability, LDH release, and DNA fragmentation. Cells were exposed to solvents for
      96 hrs. Toluene and p-xylene reduced cell viability and increased DNA
      fragmentation. LDH release was unchanged. These data indicates that long-term
      exposure to organic solvents is associated with proximal tubule cell apoptosis,
      which may be the mechanism of progressive renal fibrosis and renal failure in
      patients with high solvent exposure.

PMID- 15573477
TI  - EPG therapy for children with long-standing speech disorders: predictions and
      outcomes.
AB  - This paper reports on a project using a series of single subjects to investigate
      the effectiveness of using electropalatography (EPG) in treating ten children
      with persisting speech difficulties of no known organic aetiology. The aims of
      the project were two-fold, firstly to assess whether the subjects selected
      benefited from this treatment, and secondly to investigate whether it was
      possible to predict which children would make maximum improvement. A number of
      factors were identified as possible predictors for successful EPG therapy and
      subjects were then ranked according to these predictions. Baseline measures of
      each subject's speech were taken using word lists. Scores reflected the correct
      number of realizations of consonants produced by each subject. Subjects received
      the same number of therapy sessions and were then re-tested. Scores before and
      after therapy were compared and found to be significantly different although the
      initial predictions as to the magnitude of improvement for each subject were not
      verified. The selection of appropriate candidates for therapy and the need for
      objective means of establishing effectiveness are discussed.

PMID- 15573478
TI  - Advances in EPG for treatment and research: an illustrative case study.
AB  - Electropalatography (EPG), a technique which reveals tongue-palate contact
      patterns over time, is a highly effective tool for speech research. We report
      here on recent developments by Articulate Instruments Ltd. These include hardware
      for Windows-based computers, backwardly compatible (with Reading EPG3) software
      systems for clinical intervention and laboratory-based analysis for EPG and
      acoustic data, and an enhanced clinical interface with client and file management
      tools. We focus here on a single case study of a child aged 10+/-years who had
      been diagnosed with an intractable speech disorder possibly resulting ultimately
      from a complete cleft of hard and soft palate. We illustrate how assessment,
      diagnosis and treatment of the intractable speech disorder are undertaken using
      this new generation of instrumental phonetic support. We also look forward to
      future developments in articulatory phonetics that will link EPG with ultrasound
      for research and clinical communities.

PMID- 15573479
TI  - Articulatory placement for /t/, /d/, /k/ and /g/ targets in school age children
      with speech disorders associated with cleft palate.
AB  - This study used electropalatography (EPG) to identify place of articulation for
      lingual plosive targets /t/, /d/, /k/ and /g/ in the speech of 15 school age
      children with repaired cleft palate. Perceptual judgements indicated that all
      children had correct velar placement for /k/, /g/ targets, but /t/, /d/ targets
      were produced as errors involving palatalization or velar placement. An EPG
      classification scheme identified alveolar, palatal and velar placement.
      Articulations involving contact in alveolar and velar regions simultaneously were
      identified as alveolar velar double articulations (AVDAs). The classification
      revealed that AVDAs were relatively frequent, with 28% of alveolar and 12% of
      velar targets affected, and ten out of the 15 children produced one or more of
      these abnormal articulations. The majority of children had variable placements,
      with alveolar more variable than velar targets. The positive finding from the EPG
      data revealed that most children with perceptual errors for /t/, /d/ were able to
      make closure in the alveolar region during at least some of their attempts to
      articulate these targets. It is argued that appropriate analysis and
      interpretation of EPG data provide clinically relevant information about tongue
      placement in cleft palate speech.

PMID- 15573480
TI  - Connected speech processes in developmental speech impairment: observations from
      an electropalatographic perspective.
AB  - This paper uses a combination of perceptual and electropalatographic (EPG)
      analysis to explore the presence and characteristics of connected speech
      processes in the speech output of five older children with developmental speech
      impairments. Each of the children is shown to use some processes typical of
      normal speech production but also to use a range of more unusual processes at
      word junctures, with both inter- and intra-speaker variability apparent in the
      data. The findings suggest that the traditional focus on single word production
      in the assessment of developmental speech disorders needs to be modified to allow
      more extensive consideration of speech production in spontaneous speech.

PMID- 15573481
TI  - Articulatory variability during consonant production by Greek speakers with
      hearing impairment: an electropalatographic study.
AB  - This study uses the technique of electropalatography to investigate lingual
      palatal contact patterns during the production of the consonants /t, k, s, x, n,
      l, [symbol: see text] by four Greek speakers with profound hearing impairment and
      with differences in the intelligibility of their speech. The study provides a
      detailed description of their tongue-palate contact patterns and discusses some
      of the articulatory parameters that differentiate consonantal articulation
      between speakers with normal hearing and hearing impairment. Deviant patterns
      were found for the majority of consonants and involved substitutions,
      distortions, and epenthesis of segments. The segments that deviated from normal
      for all speakers were the fricative /s/, the palatal obstruents [c] and [c], and
      the tap [symbol: see text]. Significant differences in articulatory variability
      during consonantal production were also found. The study discusses deviant
      patterns in consonant production in relation to the differences in
      intelligibility among the speakers and with reference to data from previous
      studies.

PMID- 15573482
TI  - Introducing the pressure-sensing palatograph--the next frontier in
      electropalatography.
AB  - PRIMARY OBJECTIVE: To extend the capabilities of current electropalatography
      (EPG) systems by developing a pressure-sensing EPG system. An initial trial of a
      prototype pressure-sensing palate will be presented. RESEARCH DESIGN: The
      processes involved in designing the pressure sensors are outlined, with Hall
      effect transistors being selected. These units are compact, offer high
      sensitivity and are inexpensive. An initial prototype acrylic palate was
      constructed with five embedded pressure sensors. Syllable repetitions were
      recorded from one adult female. MAIN OUTCOMES, RESULTS AND FUTURE DIRECTIONS: The
      pressure-sensing palate was capable of recording dynamic tongue-to-palate
      pressures, with minimal to no interference to speech detected perceptually. With
      a restricted number of sensors, problems were encountered in optimally
      positioning the sensors to detect the consonant lingual pressures. Further
      developments are planned for various aspects of the pressure-sensing system.
      CONCLUSIONS: Although only in the prototype stage, the pressure-sensing palate
      represents the new generation of EPG. Comprehensive analysis of tongue-to-palate
      contacts, including pressure measures, is expected to enable more specific and
      effective therapeutic techniques to be developed for a variety of speech
      disorders.

PMID- 15573483
TI  - Phonetic and phonological analysis of progressive speech degeneration: a case
      study.
AB  - In this paper we report on an adult male participant with a rare form of
      progressive speech degeneration. We present acoustic phonetic data on his vowel
      and consonant production, and describe his prosody and syllable structure. We
      suggest possible phonological analyses of his speech, concluding that a gestural
      approach to phonology best characterizes his speech production and its
      degeneration.

PMID- 15573484
TI  - Reliability and applicability of aerodynamic measures in dysphonia assessment.
AB  - Aerodynamic measures are frequently used to analyse and document pathological
      voices. Some normative data are available for speakers from the English-speaking
      population. However, no data are available yet for Chinese speakers despite the
      fact that they are one of the largest populations in the world. The high
      variability of aerodynamic measures between and within subjects raises the issue
      of reliability and usefulness of this procedure in discriminating between normal
      and pathological voices. This study aimed to investigate the use of mean airflow
      rate and sub-glottal pressure in predicting normal and pathological voices. It
      also aimed to determine whether a higher number of repeated airflow measures
      would provide a better representation of the normative data in distinguishing
      normal from abnormal voices. The study provided a small set of preliminary
      normative data for Chinese speakers. Aerodynamic measures were collected from 56
      Cantonese female adults using a Kay Elemetrics Aerophone II. The results showed
      that the accuracy in predicting a voice to be dysphonic or normal using
      aerodynamic measures was as high as 91.1%. The accuracy was found to improve when
      the number of measurements for each aerodynamic parameter was increased from
      three to five. The overlapping of data between the dysphonic and non-dysphonic
      groups, however, suggests that the aerodynamic measures should be used as an
      adjunct to assessment of voice disorders rather than as a diagnostic tool alone.

PMID- 15573485
TI  - Organic and performance components in vocal and non-vocal communication: unifying
      concepts of description and interpretation.
AB  - This paper explores some conceptual and descriptive parallels between vocal and
      non-vocal communication, paying particular attention to the physical phenomena
      and semiotic functions in both speech and gesture. The discussion focuses on the
      interplay between organic and performance components of speech and gestural
      behaviour. A central thesis of the paper is that dilemmas of semiotic attribution
      are likely to arise when a person's organic state constrains or alters their
      communicative behaviour, especially if the listener or observer is unaware of
      that organic state. This thesis is illustrated by a discussion of the changes in
      communicative behaviour that may result from the physical modifications and
      movement constraints that are typically associated with old age or with selected
      disorders of movement. The paper concludes that a more integrated programme of
      research into comparable descriptive and theoretical concepts would offer a
      timely and fresh perspective on both speech and gesture, and their semiotic role
      in conversational interaction.

PMID- 15573486
TI  - The uniqueness of speech among motor systems.
AB  - This paper considers evidence that the speech muscles are unique in their
      genetic, developmental, functional and phenotypical properties. The literature
      was reviewed using PubMed, ScienceDirect, ComDisDome and other literature
      retrieval systems to identify studies reporting on the craniofacial and laryngeal
      muscles. Particular emphasis was given to studies of muscle fibre composition. A
      number of studies on mandibular, lingual, palatal and laryngeal muscles in humans
      show that these muscles are distinct from limb and other muscles. These speech
      related muscles typically contain diverse fibre types and these types can vary
      regionally within a muscle. In general, the muscles of the speech production
      system are designed for fast and/or variable contraction and fatigue resistance.
      The craniofacial and laryngeal muscles are unique among the muscle systems of the
      human body and the specialized properties of these muscles are relevant to
      understanding the biomechanics of speech and various speech disorders.

PMID- 15573487
TI  - Functional segments in tongue movement.
AB  - The tongue is a deformable object, and moves by compressing or expanding local
      functional segments. For any single phoneme, these functional tongue segments may
      move in similar or opposite directions, and may reach target maximum
      synchronously or not. This paper will discuss the independence of five proposed
      segments in the production of speech. Three studies used ultrasound and tagged
      Cine-MRI to explore the independence of the tongue segments. High correlations
      between tongue segments would suggest passive biomechanical constraints and low
      correlations would suggest active independent control. Both physiological and
      higher level linguistic constraints were seen in the correlation patterns.
      Physiological constraints were supported by high correlations between adjacent
      segments (positive) and distant segments (negative). Linguistic constraints were
      supported by segmental correlations that changed with the phonemic content of the
      task.

PMID- 15573488
TI  - Gradient change in the acquisition of phonology.
AB  - The prevailing view of phonological development is that changes in pronunciation
      are driven by phonological changes. This view (it is argued here) derives from
      the particular form of the data that has most often been used in studies of
      phonological development, namely broad phonetic transcriptions. Transcribing an
      earlier pronunciation with one phoneme symbol and a later pronunciation with a
      different symbol encourages the interpretation that the child has made a flip
      from one category to another. However, broad transcriptions may have
      misrepresented the facts of speech development. We review some auditory-based
      studies which have used a more fine-grained phonetic transcription and discuss
      the significance of findings on the development of long-lag plosives. We argue
      that gradient change is the typical fashion in which children's speech output
      development progresses; that it is therefore not appropriate to use rules of the
      sort that are employed for morphophonemic alternations in adult phonology to
      explain revisions over time in children's pronunciations; and that a child's
      speech output is not the best guide to their phonology.

PMID- 15573489
TI  - The interface between phonetic and lexical abilities in early Cantonese language
      development.
AB  - Data from the Cantonese Communicative Development Inventory (CCDI) is used to
      review the phonological preferences of younger (16-22 months) and older (23-30
      month) groups of children in the lexical items they are reported to be able to
      say. Analogous results to those found for English emerge from the Cantonese data:
      the younger group display selectivity in the initial consonants of words they
      say, and their preferences accord with developmental tendencies in Cantonese
      phonology. From children whose scores fell below the tenth percentile of the
      CCDI, a subset were followed up 1 year later and their linguistic progress
      evaluated. Only a proportion of these children were below still below the tenth
      percentile for vocabulary at follow-up. Their lexical immaturities were
      accompanied by limited phonetic abilities. The implications of the findings are
      discussed.

PMID- 15573490
TI  - 'Fortis/lenis' revisited one more time: the aerodynamics of some oral stop
      contrasts in three continents.
AB  - The terms fortis and lenis are variously regarded as having one single underlying
      phonetic correlate or many. An exploratory analysis of acoustic and aerodynamic
      data on contrasting stop series in a number of European and non-European
      languages confirms that a significant variation in peak intra-oral pressure and
      in articulatory stricture duration are two of the main factors differentiating
      these series. Two central questions are: (1) Is the contrast in peak pressure
      controlled by lung volume decrement or by the degree of glottal aperture? (2) Is
      the gesture for the lenis sound a truncated or a re-scaled version of the gesture
      for the fortis sound? A more detailed examination of the data from the non
      European languages suggests that glottal aperture, rather than respiratory effort
      is the main physiological parameter underlying the pressure variation, and that
      each member of the opposition has a specific target peak pressure, rather than
      the lenis peak pressure being truncated by the early release of the articulatory
      closure.

PMID- 15573491
TI  - Speaker-specific kinematic properties of alveolar reductions in English and
      German.
AB  - A simultaneous EPG/EMA study of tongue gestures of five speakers was conducted to
      investigate the kinematic events accompanying alveolar stop reductions in the
      context of a velar plosive /k/ and in the context of a laryngeal fricative /h/ in
      two languages, English and German. No systematic language differences could be
      detected. Alveolar productions before a following /h/ showed only a marginal
      weakening of the formation of complete occlusion, while alveolar productions
      before a following /k/ showed a wide range of reductions, including instances of
      a complete deletion of the alveolar gesture. The extension of movement reduction
      varied between and within subjects. Importantly, while speakers were consistent
      with themselves, they employed different articulatory patterns with respect to
      the timing relationship between movement initiation, overall movement duration,
      peak velocity as well as closure duration. An attempt is made to relate the
      observed movement patterns to the dynamic factors of the speech mechanism.

PMID- 15573492
TI  - An EMA/EPG study of vowel-to-vowel articulation across velars in Southern British
      English.
AB  - Recent studies have attested that the extent of transconsonantal vowel-to-vowel
      coarticulation is at least partly dependent on degree of prosodic accentuation,
      in languages like English. A further important factor is the mutual compatibility
      of consonant and vowel gestures associated with the segments in question. In this
      study two speakers of standard southern British English produced sequences of
      [symbols: see text] sequences where the identity of V was either /i/ or /a/, and
      nuclear accent placement was varied systematically. A combined technique of EPA
      and EMA was used, as well as spectrographic measures. Results indicate that there
      were only minimal transconsonantal coarticulatory effects between the two full
      vowels /i/ and /a/, but there was evidence of dissimilation of the flanking
      vowels, particularly in /'kaki/ and /'kika/ sequences, suggesting that
      prosodically strong vowels resist vowel-to-vowel coarticulation. Initial schwa,
      however, was highly coarticulated with following /a/ and /i/, and the spatial
      extent of this coarticulatory effect was correlated with degree of accentuation,
      particularly in the case of a following /i/ vowel. The velar stops showed a high
      level of coarticulation with flanking /i/ vowels, supporting earlier claims by
      Fowler and Brancazio, that this consonant is 'less' resistant to coarticulatory
      pressures than others in English.

PMID- 15573493
TI  - Darkness in [l] as a scalar phonetic property: implications for phonology and
      articulatory control.
AB  - Dorsopalatal contact and F2 data for speakers of dialectal groups with dark [1]
      (Majorcan Catalan, Eastern Catalan) and clear [l] (German, Catalan from the
      Valencia region) provide some support for the hypothesis that degree of
      velarization or pharyngealization in the alveolar lateral consonant does not
      proceed categorically but gradually across dialects. Indeed, F2 frequency data
      for [l] in the context of [i] reveal that darkness does not distinguish the two
      dialectal groups but varies gradually from dialects with a very dark realization
      of [l] (Mallorqui) to those with a very clear realization (Valencia) through
      dialects exhibiting intermediate degrees of darkness (Eastern Catalan, German). A
      similar scenario applies to the [a] context. This finding questions the complex,
      two-gestural status of dark [l] and the notion that dark [l] should always be
      more coarticulation resistant than clear [l].

PMID- 15573494
TI  - On the distinction between Norwegian [symbols: see text] from a phonetic
      perspective.
AB  - The present study uses electropalatography (EPG) and electromagnetic
      articulography (EMA) in the description of the articulation of the two East
      Norwegian fricatives [symbols: see text] in the speech of seven normal adult
      speakers. The motivation for studying these two phonemes is twofold: there is a
      merger between the places of articulation of these two fricatives in the speech
      of the young. A description of the articulation in the speech of mature speakers
      who have the distinction, may throw light on the mechanisms behind the merger.
      Furthermore, identifying possible articulatory variation between normal speakers
      is important in order to establish an articulatory base line for clinical work.
      Our investigation has shown considerable overlap between the phonetic
      realizations of the two phonemes, as well as substantial variation between
      speakers in their articulation. There is, however, a clear acoustic distinction
      between the two phonemes for all speakers, and the acoustic patterns between
      speakers are similar.

PMID- 15573495
TI  - The potential of photochemical transition metal reactions in prebiotic organic
      synthesis. I. Observed conversion of methanol into ethylene glycol as possible
      prototype for sugar alcohol formation.
AB  - Photochemical processes involving redox reactions between metal ions and organic
      substrates possess the versatile potential for having harnessed solar energy for
      prebiotic organic synthesis. The present study in our Laboratory has shown that
      ultraviolet irradiation of transition metal ions such as of Ni, Co, Fe, Cu and Ti
      dissolved in primary or secondary alcohols causes photoreduction of the metal
      ions with the concomitant oxidation of the alcohol to aldehyde or ketone. An
      observed accompaniment of this novel 'light' reaction has been the known 'dark'
      pinacol reaction, whereby the carbonyl derivative underwent bimolecular coupling
      to the diol by the photogenerated reduced transition metal reagent. These tandem
      'light-dark' processes possess the potential for the stepwise synthesis of
      dimeric 1,2-diols from simpler alcohols under conditions that might have
      prevailed on the prebiotic earth. Experiments reported here have demonstrated
      that such a tandem 'light-dark' conversion of methanol into ethylene glycol, via
      formaldehyde, does in fact occur, when nickel(II) acetylacetonate solutions in
      methanol undergo prolonged irradiation at 185-254 nm. Since ethylene glycol can
      be considered as the simplest sugar alcohol, these findings may provide novel
      insight into the prebiotic oligomerization of formaldehyde into higher sugar
      alcohols or even sugars.

PMID- 15573496
TI  - N-phosphoryl amino acids and biomolecular origins.
AB  - The possible role of phosphoryl amino acids for biomolecular origins is briefly
      reviewed. Peptide formation, ester formation, ester exchange on phosphorus and N
      to O migration occurred when the N-phosphoryl amino acid was incubated at room
      temperature. Short nucleotides and peptides were formed when nucleoside was
      reacted with N-phosphoryl amino acid at room temperature. Serine and threonine
      residues in their conjugate with different nucleosides (mediated with phosphorus)
      showed different self-cleavage activities. N-phosphoryl Histine and Ser-His
      dipeptide could cleave nucleic acids, proteins and esters in neutral medium.
      Based on a simple model, a pathway of 'co-evolution of protein and nucleic acid'
      was proposed.

PMID- 15573497
TI  - Phosphorylation of nucleotide molecules in hydrothermal environments.
AB  - Phosphorylation of AMP into ADP and ATP, that can outrun their hydrolysis, was
      made possible in a simulated hydrothermal environment when trimetaphosphate was
      used as the phosphate source. The best yields of phosphorylated products were
      obtained when the reaction fluids whose temperature was set at about 100 degrees
      centigrade was injected into the cold environment maintained at 0 degree in a
      recycling manner. Hydrothermal environments in the primitive ocean could also
      have served as prebiotic sites for phosphorylation, among others.

PMID- 15573498
TI  - Kinetics of organic transformations under mild aqueous conditions: implications
      for the origin of life and its metabolism.
AB  - The rates of thermal transformation of organic molecules containing carbon,
      hydrogen, and oxygen were systematically examined in order to identify the
      kinetic constraints that governed origin-of-life organic chemistry under mild
      aqueous conditions. Arrhenius plots of the kinetic data were used to estimate the
      reaction of half-lifes at 50 degrees C. This survey showed that hydrocarbons and
      organic substances containing a single oxygenated group were kinetically the most
      stable; whereas organic substances containing two oxygenated groups in which one
      group was an alpha- or beta-positioned carbonyl group were the most reactive.
      Compounds with an alpha- or beta-positioned carbonyl group (aldehyde or ketone)
      had rates of reaction that were up to 10(24)-times faster than rates of similar
      molecules lacking the carbonyl group. This survey of organic reactivity, together
      with estimates of the molecular containment properties of lipid vesicles and
      liquid spherules, indicates that an origins process in a small domain that used
      C,H,O-intermediates had to be catalytic and use the most reactive organic
      molecules to prevent escape of its reaction intermediates.

PMID- 15573499
TI  - Kinetic analysis of self-replicating peptides: possibility of chiral
      amplification in open systems.
AB  - A simplified kinetic model scheme is presented that addresses the main reactions
      of two recently reported peptide self-replicators. Experimentally observed
      differences in the autocatalytic efficiency between these two systems-- caused by
      variations in the peptide sequences--and the possible effect of chiral
      amplification under heterochiral reaction conditions were evaluated. Our
      numerical simulations indicated that differences in the catalytic performance are
      exclusively due to pronounced variations in the rate parameters that control the
      reversible and hydrophobic interactions in the reaction system but neither to
      alterations in the underlying reaction network nor to changes in the
      stoichiometry of the involved aggregation processes. Model predictions further
      demonstrated the possible existence of chiral amplification if peptide self
      replication is performed under heterochiral reaction conditions. Pointing into
      the direction of a possible cause for biomolecular homochirality, it was found
      that in open flow reactors, keeping the system under non-equilibrium conditions,
      a remarkable amplification of enantiomeric excess could be achieved. According to
      our modeling, this is due to a chiroselective autocatalytic effect and a meso
      type separation process both of which are assumed to be intrinsic for the
      underlying dynamics of heterochiral peptide self-replication.

PMID- 15573500
TI  - Importance of biologically active aurora-like ultraviolet emission: stochastic
      irradiation of Earth and Mars by flares and explosions.
AB  - Habitable planets will be subject to intense sources of ionizing radiation and
      fast particles from a variety of sources--from the host star to distant
      explosions--on a variety of timescales. Monte Carlo calculations of high-energy
      irradiation suggest that the surfaces of terrestrial-like planets with thick
      atmospheres (column densities greater than about 100 g cm(-2)) are well protected
      from directly incident X-rays and gamma-rays, but we find that sizeable fractions
      of incident ionizing radiation from astrophysical sources can be redistributed to
      biologically and chemically important ultraviolet wavelengths, a significant
      fraction of which can reach the surface. This redistribution is mediated by
      secondary electrons, resulting from Compton scattering and X-ray photoabsorption,
      the energies of which are low enough to excite and ionize atmospheric molecules
      and atoms, resulting in a rich aurora-like spectrum. We calculate the fraction of
      energy redistributed into biologically and chemically important wavelength
      regions for spectra characteristic of stellar flares and supernovae using a Monte
      Carlo transport code and then estimate the fraction of this energy that is
      transmitted from the atmospheric altitudes of redistribution to the surface for a
      few illustrative cases. For atmospheric models corresponding to the Archean
      Earth, we assume no significant ultraviolet absorbers, only Rayleigh scattering,
      and find that the fraction of incident ionizing radiation that is received at the
      surface in the form of redistributed ultraviolet in the biologically relevant 200
      320 nm region (UV-C and UV-B bands) can be up to 4%. On the present-day Earth
      with its ultraviolet ozone shield, this fraction is found to be 0.2%. Both values
      are many orders of magnitude higher than the fraction of direct ionizing
      radiation reaching the surface. This result implies that planetary organisms will
      be subject to mutationally significant, if intermittent, fluences of UV-B and
      harder radiation even in the presence of a narrow-band ultraviolet shield like
      ozone. We also calculate the surficial transmitted fraction of ionizing radiation
      and redistributed ultraviolet radiation for two illustrative evolving Mars
      atmospheres whose initial surface pressures were 1 bar. We discuss the frequency
      with which redistributed ultraviolet flux from parent star flares exceeds the
      parent star ultraviolet flux at the planetary surface. We find that the
      redistributed ultraviolet from parent star flares is probably a fairly rare
      intermittent event for habitable zone planets orbiting solar-type stars except
      when they are young, but should completely dominate the direct steady ultraviolet
      radiation from the parent star for planets orbiting all stars less massive than
      about 0.5 solar masses. Our results suggest that coding organisms on such planets
      (and on the early Earth) may evolve very differently than on contemporary Earth,
      with diversity and evolutionary rate controlled by a stochastically varying
      mutation rate and frequent hypermutation episodes.

PMID- 15573501
TI  - [Tracking, evaluating: 3 to 5 minutes for fundamental clinical observation in
      nutritional management].

PMID- 15573502
TI  - [Simplified malnutrition screening tool: Malnutrition Universal Screening Tool
      (MUST)].
AB  - MUST (Malnutrition Universal Screening Tool) is a nutritional screening tool easy
      to use by any trained care-giver and valid for any adult patient. It considers
      body mass index, weight change and acute disease effect equally and determines a
      malnutrition risk score. If necessary, anthropometric measures may be simpliyfied
      by alternative methods. MUST is reliable between different healthcare settings et
      promotes detection and management of malnutrition during the patient medical
      course.

PMID- 15573503
TI  - [Subjective Global Assessment (SGA): evaluation and followup of nutritional
      state].
AB  - The subjective global assessment (SGA) defines nutritional and functional status
      of patients with the aim of identifying who could benefit from a nutritional
      intervention. The SGA was designed to evaluate the nutritional risk of infectious
      complications among the surgical patients. Later on, it became largely utilized
      to evaluate the nutritional status of other groups of patients, because it is
      reliable and easy to use. However, it is important to verify that the SGA is an
      adequate test also in other clinical situations. This review analyses recent
      literature regarding the actual utilization of the SGA in clinical situations
      frequently associated to malnutrition: kidney diseases, AIDS, cancer, aging. The
      reproducibility of SGA depends on the experience of the caregiver administering
      it. Its validation compared to more objective parameters like visceral proteins
      or body composition is not always obvious. In several studies the SGA does not
      seem enough sensitive to detect a beginning of malnutrition. Its specificity and
      predictive validity were demonstrated in all of the clinical situations analyzed.
      In conclusion, the SGA is a tool adequate to identify patients with a nutritional
      risk and who would benefit of a nutritional intervention aiming at preventing
      associated complications.

PMID- 15573504
TI  - [Role of impedance measurement in nutritional screening].
AB  - Nutritional status has a prognostic value in the clinical evolution of patients
      who are malnourished, are becoming malnourished or are in process of being
      rehabilitated. The evaluation of nutritional status is based on a comprehensive
      approach, and includes body composition measurement by bio-impedance analysis
      (BIA). BIA determines the quantity of body fat-free and fat mass and has a
      precision around 4%. The reliability of BIA depends on the use of body
      composition prediction equations that are adapted to the subjects studied and on
      the inclusion of various anthropometric parameters (weight, height, sex, age,
      race, etc). BIA remains imprecise in the presence of abnormal distribution of
      body compartments (ascites, dialysis, lipodystrophy) or of extreme weights
      (cachexia, severe obesity). Multi-frequency or segmental BIA were developed to
      overcome hydration abnormalities and variations in body geometry. However, these
      techniques require further validation. This review discusses the indications and
      limitations of BIA.

PMID- 15573505
TI  - [Screening and treatment of malnutrition: European Council Resolution and its
      potential application in Switzerland].
AB  - The deleterious consequences of hospital malnutrition are progressively being
      recognized by the public. The Committee of the Ministers of the European Council
      has released a resolution for food and nutrition and ask the state members to
      apply national recommendations in their hospitals. The evaluated domains and
      actions to be undertaken are based on 4 elements: Access to a healthy and varied
      food supply is a fundamental human right; a high number of patients hospitalized
      in Europe are malnourished (30-60%); the demonstration that malnutrition of
      hospitalized patients increases length of hospital stay and medical costs; the
      demonstrated beneficial effects of a hospital food service and of optimal
      nutritional care on morbidity, healing and quality of life. The resolution
      indicates clearly the options to be followed to optimize the actions and
      decisions at three levels: patient care, support services, and administration.
      All caregivers must be involved in the implementation of the recommendations in a
      way to adapt them to the local needs and restrictions. This review summarizes the
      actions to be taken by medical and other caregivers in order to sensitize them to
      the above-mentioned problems and to initiate practical options to treat
      malnourished patients or patients at risk of becoming malnourished.

PMID- 15573507
TI  - [Dysphagia and nutritional treatment: decision tree].
AB  - Dysphagia is very frequent in hospitals and the geriatric population. It leads to
      serious physical and psychological consequences such as aspiration, lung
      infection, progressive undernutrition which all impair the quality of life and
      the survival. Early diagnosis and appropriate treatment of dysphagia are
      therefore essential to avoid or minimize these complications which increase the
      length of hospital stay and cost. This review describes the symptoms and the
      clinical approach of dysphagia. The importance of informing and sensitizing all
      the health care providers to this pathology is highlighted. It also emphazised
      the need of an interdisciplinary management of dysphagia, including the dietetic
      approach.

PMID- 15573508
TI  - [Metabolic adaptation to hypoxia: chronic obstructive pulmonary disease and high
      altitude].
AB  - The effect of oxygen in modulating metabolism has been largely investigated in
      vitro and in animal studies, but very little in humans. Body weight loss and
      muscle fatigability is a common finding in chronic obstructive pulmonary
      diseases, often difficult to reverse despite an optimal nutritional intake. The
      aim of this paper is to review recent literature regarding pathological and
      physiological situations characterized by hypoxia exposure, particularly chronic
      obstructive pulmonary diseases and high altitude staying.

PMID- 15573509
TI  - [Insulin, nitric oxide and the sympathetic nervous system: from crossroads to
      metabolic and cardiovascular homeostasis].
AB  - Epidemiological studies demonstrate an association between insulin resistance,
      hypertension and cardiovascular morbidity. Over the past decade, evidence has
      accumulated indicating that short-term insulin administration, in addition to its
      metabolic effects, also has important cardiovascular actions. The sympathetic
      nervous system and the L-arginine-nitric oxide pathway have emerged as central
      players in the mediation of insulin's cardiovascular actions. The underlying
      mechanisms and the factors that may govern the interaction between insulin and
      these two major cardiovascular regulatory systems have been studied extensively
      in healthy people and insulin-resistant subjects. Here we summarize the current
      understanding and gaps in knowledge on insulin's cardiovascular actions in
      humans, and discuss possible pathophysiological consequences of their alteration.
      Based on recent new insight, we propose that a genetic and/or acquired defect of
      nitric oxide synthesis could represent a central defect triggering many of the
      metabolic, vascular and sympathetic abnormalities characteristic of insulin
      resistant states, all of which may predispose to cardiovascular disease.

PMID- 15573510
TI  - [NO, a major regulator of metabolic and cardiovascular homeostasis].
AB  - Obesity and insulin resistance are reaching epidemic proportions worldwide. Over
      the past decade, nitric oxide (NO) has emerged as a key player in the regulation
      of the metabolic and cardiovascular homeostasis. Here we will review recent data
      obtained in mice with disruption of the genes encoding for each of the three
      nitric oxide synthase isoforms. These data demonstrate that both defective and
      augmented NO synthesis have detrimental effects on the regulation of the
      metabolic and cardiovascular system. These observations provide the rationale for
      the use of NO-donors and/or inhibitors of NO overproduction in the treatment of
      insulin resistance.

PMID- 15573511
TI  - [Nitric oxide donors, a new treatment for insulin resistance, metabolic syndrome
      and diabetes?].
AB  - Obesity/insulin resistance ("diabesity") and the associated long term
      complications are reaching epidemic proportions worldwide. Recent evidence in
      experimental animals and humans shows that nitric oxide (NO) plays a key role in
      glucose and cardiovascular homeostasis. Pharmaceutical drugs releasing small and
      physiological amounts of NO may represent potential new treatments for insulin
      resistance.

PMID- 15573512
TI  - [Voluntary pregnancy termination in the canton of Vaud in 2002].
AB  - No rates of pregnancy termination are available for Switzerland as a whole. In
      the canton of Vaud, however, pregnancy termination has been monitored for over
      ten years. The annual incidence (10.9 per 1000 residents in 2002) is one of the
      lowest recorded worldwide, but considerable variations are observed depending on
      age and on nationality; the incidence for non-Swiss nationals being three times
      higher than for Swiss nationals. As in the past, and in line with legislative
      changes that came into effect in October 2002, the vast majority of pregnancy
      terminations take place before the twelfth week of pregnancy. Repeat termination
      is relatively frequent: a quarter of those requesting termination in 2002
      reported previous experience of pregnancy termination. In parous women, one in
      five requests for termination occurs less than one year after the birth of the
      last child. These data indicate that contraceptive counselling should be
      reinforced at the time of childbirth and following pregnancy termination.

PMID- 15573514
TI  - Perspective. Don't waste time; provide education.

PMID- 15573513
TI  - [Demographic aging, mental health and geriatric psychiatry education].

PMID- 15573515
TI  - The Top 10 CPOE challenges.

PMID- 15573516
TI  - With CEOs and CFOs, ROI on center stage.

PMID- 15573517
TI  - Sizing up both sides of the table.

PMID- 15573518
TI  - Finding the right HIPAA mix.

PMID- 15573519
TI  - Locking down health information networks.

PMID- 15573520
TI  - Screen test yields mobile star.

PMID- 15573521
TI  - Readers' perspectives. Electronic medical records will help speed adoption of the
      technology.

PMID- 15573522
TI  - Fetal growth and development: roles of fatty acid transport proteins and nuclear
      transcription factors in human placenta.
AB  - In the feto-placental unit, preferential transport of maternal plasma arachidonic
      acid (20:4n-6) and docosahexaenoic acid (22:5n-3) across the placenta is of
      critical importance for fetal growth and development. More than 90 per cent of
      the fat deposition in the fetus occurs in the last 10 weeks of pregnancy. All of
      the n -3 and n -6 fatty acid structures acquired by the fetus have to cross the
      placenta and fetal blood are enriched in long chain polyunsaturated fatty acids
      (LCPUFA) relative to the maternal supply. Fatty acids cross the placental
      microvillous and basal membranes by simple diffusion and via the action of
      membrane bound (FAT, FATP and p-FABPpm) and cytoplasmic fatty acid-binding
      proteins (FABPs). The direction and magnitude of fatty acid flux is mainly
      dictated by the relative abundance of available binding sites. The existence of a
      fatty-acid-transport system comprising multiple binding proteins in human
      placenta may be essential to facilitate the preferential transport of maternal
      plasma fatty acids in order to meet the requirements of the growing fetus. The
      critical importance of long-chain fatty acids in cellular homeostasis demands an
      efficient uptake system for these fatty acids and their metabolism in tissues. In
      fact, involvement of several nuclear transcription factors (PPARgamma, LXR, RXR,
      and SREBP-1) is critical in the expression of genes responsible for fatty acids
      uptake, placental trophoblast differentiation and hCG production. These indicate
      that these receptors are potential regulators of placental lipid transfer and
      homeostasis. This review discusses importance of nuclear receptors and fatty acid
      binding/transport proteins in placental fatty acid uptake, transport and
      metabolism.

PMID- 15573523
TI  - Role of L-lysine HCl in adoptive immune therapy towards development of suitable
      tuberculosis vaccination.
AB  - L-Lysine HCI is being proposed to be a possible biocompatible adjuvant to enhance
      immune response by virtue of its probable non-specific bridging action and
      cellular proliferation properties. This proposal has been tried to be
      substantiated by designing an in vitro culture protocol, varying the
      concentration of L-lysine HCI and its further in vivo application. Splenic
      lymphocyte population has been extracted from mice and co-cultured with extracted
      mice macrophage population in presence of either Bacille Calmette Guerrin (BCG)
      or Hepatitis B surface antigen (HbsAg) and added L-lysine hydrochloride in
      culture media. Post incubation of these cultures, "taught" cell population has
      been adoptively transferred in naive mice. These mice were then challenged by
      respective antigen dose, Change in Immune response with this challenge was noted.
      Antibody titre was followed in all the experiments as a measure of immune
      response. In adoptive immune transfer experiment of with HbsAg (AIT-HbsAg),
      similar to that with BCG (AIT-BCG), after the incubation period, antibody titre
      was higher in added lysine containing cultures in comparison with the control
      ones. Post transfer followed by antigen challenge, in AIT-BCG the expected
      augmentation in immune response was hardly visible. But in AIT-HbsAg, with the
      help of lysine booster, the animals responded better as far as the antibody titre
      is concerned.

PMID- 15573524
TI  - Quercetin attenuates thermal hyperalgesia and cold allodynia in STZ-induced
      diabetic rats.
AB  - Neuropathic pain is one of the important microvascular complications of diabetes.
      Oxidative stress and superoxide play a critical role in the development of
      neurovascular complications in diabetes. Aim of the present study was to evaluate
      the effect of quercetin, a bioflavonoid on thermal nociceptive responses in
      streptozotocin (STZ)-induced diabetic rats assessed by tail-immersion and hot
      plate methods. After 4-weeks of a single intravenous STZ injection (45 mg/kg body
      weight), diabetic rats exhibited a significant thermal hyperalgesia and cold
      allodynia along with increased plasma glucose and decreased body weights as
      compared with control rats. Chronic treatment with quercetin (10 mg/kg body
      weight; p.o) for 4-weeks starting from the 4th week of STZ-injection
      significantly attenuated the cold allodynia as well as hyperalgesia. Results
      indicate that quercetin, a natural antioxidant, may be helpful in diabetic
      neuropathy.

PMID- 15573525
TI  - Clenbuterol treatment stimulates cell proliferation in denervated chick
      gastrocnemius muscle.
AB  - Daily administration of clenbuterol, a beta adrenoceptor agonist (0.5 mg/kg body
      weight; for 7 days) to normal innervated and denervated adult chicks (Gallus
      domesticus) resulted in different growth related responses by gastrocnemius
      muscle. While normal innervated muscle undergoes hypertrophy, structural
      reorganization in denervated tissue is accomplished by the de novo emergence of
      new cells. A contrasting cell population with extremely narrow cross sectional
      dimensions is a characteristic feature of denervated muscle in presence of
      clenbuterol. Measurement of fiber dimensions, number of cells per unit area and
      examination of histochemical preparations support this.

PMID- 15573526
TI  - Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in
      fibrosarcoma bearing rats.
AB  - Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body
      wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats.
      Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD),
      glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of
      lipid peroxidation (LPO) in the liver and kidney tissues were assessed. A
      significant increase was noted for the rate of LPO with a corresponding decrease
      in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma
      bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase
      (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid
      (SA) were increased in the serum. Treatment with B. monniera extract
      significantly increased the antioxidant enzyme status, inhibited lipid
      peroxidation and reduced the tumor markers. It can be concluded that B.monniera
      extract promotes the antioxidant status, reduces the rate of lipid peroxidation
      and the markers of tumor progression in the fibrosarcoma bearing rats.

PMID- 15573527
TI  - Effect of bamboo shoot, Bambusa arundinacea (Retz.) Willd. on thyroid status
      under conditions of varying iodine intake in rats.
AB  - Young shoots or sprouts of common bamboos are used as food in third world
      countries. Evidences suggest the presence of cyanogenic glucoside like anti
      thyroidal substance in bamboo shoots (BS) but effect of prolonged BS consumption
      on thyroid status under conditions of varying iodine nutriture remains
      unexplored. The study was undertaken to evaluate goitrogenic content, in vitro
      anti thyroid peroxidase (TPO) activity and in vivo anti thyroid potential of BS
      with and without extra iodide. Fresh BS contains high cyanogenic glucoside (551
      mg/kg), followed by thiocyanate (24mg/kg) and glucosinolate (9.57mg/kg). In vitro
      inhibition in TPO activity was found with raw, raw boiled and cooked extracts.
      Inhibition constant (IC50) and PTU equivalence of fresh BS were 27.5+/-0.77
      microg and 3.27 respectively. Extra iodide in the incubation media reduced TPO
      inhibition induced by BS but could not cancel it. Thyroid weight, TPO activity
      and total serum thyroid hormone levels of BS fed animals for 45 and 90 days
      respectively were determined and compared with controls. Significant increase in
      thyroid weight as well as higher excretion of thiocyanate and iodine along with
      marked decrease in thyroid peroxidase activity, T4 and T3 levels were observed in
      BS fed group. Chronic BS consumption gradually developed a state of
      hypothyroidism. Extra iodide had reduced the anti-thyroidal effect of BS to an
      extent but could not cancel it because of excessive cyanogenic glucoside,
      glucosinolate and thiocyanate present in it.

PMID- 15573528
TI  - Effect of aqueous leaf extract of Irvingia gabonensis on gastrointestinal tract
      in rodents.
AB  - Effect of the aqueous leaf extract of I. gabonensis on the gastrointestinal tract
      was investigated on isolated rabbit jejunum, guinea pig ileum, gastrointestinal
      motility, castor oil-induced diarrhoea in mice and castor oil-induced fluid
      accumulation in rats. The results showed that the extract exhibited a
      concentration-dependent relaxation of spontaneous pendular movement of isolated
      rabbit jejunum and guinea pig ileum, and attenuated both acetylcholine-induced
      contraction of rabbit jejunum and histamine-induced contraction of guinea pig
      ileum. The extract (100, 200 and 400 mg/kg) also caused a significant dose
      dependent decrease of gastrointestinal motility in mice (40.12, 39.45 and
      37.45%), intestinal fluid accumulation in rats (71.43, 81.63 and 83.27%), and
      remarkably protected mice against castor oil-induced diarrhoea [58.33, 75 and
      91.67% (Di Carlo score)] respectively. Preliminary phytochemical screening of the
      aqueous leaf extract of I. gabonensis revealed the presence of saponins, tannins,
      phenols and phlobatanins.

PMID- 15573529
TI  - Effect of Coscinium fenestratum on hepatotoxicity in rats.
AB  - Anti-hepatotoxic activity of methanol extract of Coscinium fenestratum stem (MEC)
      was investigated against carbon tetrachloride-induced hepatopathy in rats.
      Hepatotoxic rats were treated with MEC for a period of 90 days (60mg/kg body
      weight, daily, orally by intubation). Anti-hepatotoxic effect was studied by
      assaying the activities of serum marker enzymes like aspartate aminotransferase,
      alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase,
      lactate dehydrogenase etc. and glucose (6) phosphate dehydrogenase in liver. We
      also estimated the concentrations of total proteins, total lipids, triglycerides,
      phospholipids and cholesterol in serum, liver and kidney. The activities of all
      the marker enzymes registered a significant elevation in carbon tetrachloride
      treated rats, which were significantly recovered towards an almost normal level
      in animals co-administered with MEC. Other biochemical changes induced by carbon
      tetrachloride too showed reliable signs of retrieving towards the normalcy.
      Histopathological analysis confirmed the biochemical investigations. This study
      unravels the anti-hepatotoxic activity of MEC.

PMID- 15573530
TI  - Analysis of time-dependent recovery from beryllium toxicity following chelation
      therapy and antioxidant supplementation.
AB  - Efforts have been made to minimize the toxic effect caused by beryllium. Adult
      cyclic rats of Sprague Dawley strain were administered a bolus dose of 50mg/kg
      beryllium nitrate intramuscularly. The chelation therapy with glutathione (GSH),
      dimercapto propane sulfonic acid (DMPS)+ selenium (Se) and D-Penicillamine (DPA)
      + Se was given for 3 days followed by a rest of 1,3 and 7 days respectively. The
      results revealed a significant fall in the blood sugar level, serum alkaline
      phosphatase activity, serum proteins. A significant rise in the transaminases
      i.e. aspartate aminotranferase and alanine aminotranferase pattern is indicative
      of leakage of enzymes from liver resulting in alterations in the cell
      permeability. A rise in the hepatic lipid peroxidation activity is a direct
      indication of oxidative damage resulting in free radical generation. Results of
      the distribution studies by atomic absorption spectrophotometry reveal an
      increased concentration of beryllium in liver and kidney followed by lung and
      uterus. The relative ability of 3 chelating agents to act as antagonists for
      acute beryllium poisoning have been examined in liver, kidney, lungs and uterus.
      The appreciable change in the beryllium concentration in various organs is
      duration-dependent during the entire period being highly significant after 7 days
      rest. From the biochemical assays, and distribution studies it can be assumed
      that DPA+Se was the most effective therapeutic agent followed by DMPS+Se and GSH.
      Thus it can be concluded that DPA+Se is a better therapeutic agent as compared to
      DMPS+Se and GSH.

PMID- 15573531
TI  - In vitro antioxidant studies of Annona squamosa Linn. leaves.
AB  - The free radical scavenging potential of the leaves of A. squamosa was studied by
      using different antioxidant models of screening. The ethanolic extract at 1000
      microg/ml showed maximum scavenging of the radical cation, 2,2-azinobis- (3
      ethylbenzothiazoline-6-sulphonate) (ABTS) observed upto 99.07% followed by the
      scavenging of the stable radical 1,1-diphenyl, 2-picryl hydrazyl (DPPH) (89.77 %)
      and nitric oxide radical (73.64%) at the same concentration. However, the extract
      showed only moderate scavenging activity of superroxide radicals and antilipid
      peroxidation potential, which was performed using rat- brain homogenate. The
      findings justify the therapeutic applications of the plant in the indigenous
      system of medicine, augmenting its therapeutic value.

PMID- 15573532
TI  - Effect of repeated intraperitoneal exposure to picrotoxin on rat liver lysosomal
      function.
AB  - Effect of repeated (20 days) exposure to picrotoxin (PTX) on rat liver lysosomal
      function was evaluated by measuring the free and total activities of acid
      phosphatase, cathepsin D, ribonuclease II (RNAse II) and deoxyribonuclease II
      (DNAse II). The free activities of the nucleases (both RNAse II and DNAse II)
      were increased following PTX exposure. The total DNAse II activity was increased
      by 2.2-fold whereas the total acid phosphatase activity was decreased by 28%.
      Consequently, the ratios of total activity / free activity were low in the PTX
      exposed groups, implying loss of membrane integrity. Cathepsin D activity was
      completely abolished. The results show that repeated exposure to PTX can lead to
      lysosomal dysfunction in liver.

PMID- 15573533
TI  - Analgesic activity of new synthetic thiazolidine-4-ones derivatives.
AB  - Ten new synthetic thiazolidine-4-ones derivatives (5 chlorothiazolidine-4-ones, 3
      methoxythiazolidine-4-ones and 2 hydoxythiazolidine-4-ones) having different
      substituents at R1, R2 and R3 were evaluated for their analgesic activity using
      different animal models and their structure activity relationship was also
      elucidated. Chlorothiazolidine-4-ones and methoxythiazolidine-4-ones exhibited
      analgesic activity in tail flick test, tail immersion test and acetic acid
      writhing test. C-III (chloride substituents at R1 and R2) produced higher
      latencies than any other compounds in tail flick test and C-I (no substituents at
      R1 and R2) was not effective in acetic acid writhing test. Hydroxythiazolidine-4
      ones did not show analgesic activity in any of the animal models used. In
      conclusion, the character of substituents at R3 of thiazolidine moiety position
      may have an effect on the analgesic activity of thiazolidine-4-ones and either
      chloride or methoxy substitution may be necessary to produce analgesic activity.
      Two chloride substituents in a compound may increase the central analgesic
      activity of the compound.

PMID- 15573534
TI  - Effect of different intensities of swimming exercise on testicular oxidative
      stress and reproductive dysfunction in mature male albino Wistar rats.
AB  - Swimming exercise for 1, 2 and 3 hr for 5 days/week for consecutive 4 weeks,
      results in a significant reduction in testicular, epididymal, prostetic, seminal
      vesicle somatic indices; epididymal sperm count, sperm motility; preleptotine
      spermatocytes, mid pachytene spermatocytes and stage 7 spermatids; plasma levels
      of testosterone, luteinizing hormone; testicular delta5, 3beta-hydroxysteroid
      dehydrogenase, 17beta-hydroxysteroid dehydrogenase; testicular superoxide
      dismutase, catalase, glutathione peroxidase, glutathione-s-transferase and
      glutathione along with significant elevation in malondialdehyde in male albino
      rats. However, no significant change was noted in final body weight,
      spermatogonia-A and plasma level of follicle stimulating hormone. The results
      that oxidative stress develops with the increasing of exercise intensity, which
      may interfere in male reproductive activities.

PMID- 15573535
TI  - Infiltration by CD4+ and CD8+ lymphocytes in bursa of chickens infected with
      Infectious Bursal Disease Virus (IBDV): strain-specific differences.
AB  - In order to investigate if there is any definite correlation between the degree
      of T-cell response in the bursa of Fabricius (BF) and the virulence of Infectious
      Bursal Disease (IBD) virus strains, chickens were infected with strains of
      different virulence i.e. mild (Lukert strain), intermediate (Georgia strain) or
      invasive intermediate (IV-95 strain). At various times post-inoculation, bursal
      samples were collected to study virus specific histopathological lesions, the
      distribution of viral antigen and the extent of T-cell infiltration in the bursa.
      Most severe bursal lesions were induced by IV-95 strain (the invasive
      intermediate strain), whereas Lukert, the mild strain caused the least severe
      lesions. The number of virus positive cells in the bursa was highest in chickens
      infected with IV-95 strain. Substantial infiltration of CD4+ and CD8+ T-cells in
      the bursal follicles of virus-infected groups was observed from 4 d.p.i. onwards.
      The magnitude of T-cell response was more in the birds infected with intermediate
      (Georgia) or invasive intermediate strains of virus than chickens inoculated with
      mild (Lukert) strain, even when 10-fold higher doses of the inoculums were used.
      PHA responses to peripheral lymphocytes were found suppressed in all the groups
      of chickens only transiently. The results indicate that the magnitude of T-cell
      responses in BF during IBDV infection is influenced more by the virulence of
      virus strain rather than the quantum of viral load in BF. Over all these studies
      may have implications in understanding the role of T-cells in pathogenesis and
      immunity in IBD.

PMID- 15573536
TI  - Production of interspecies chimeras by transplanting rosy barb (Puntius
      conchonius) embryonic cells to zebrafish (Danio rerio) embryos.
AB  - Establishment of a cell-mediated gene transfer system has potential as a new
      breeding technique for commercially valuable fishes. As an important step toward
      developing an inter-species chimera, cells from blastula-stage embryos of rosy
      barb (Puntius conchonius) were transplanted into zebrafish (Danio rerio) blastula
      stage embryos to observe the development of the recipient. From the total of 473
      transplants obtained only a fraction of 13 chimeras appeared perfectly normal
      after one month. Over two in normal 13 chimeras showed some characters from the
      donor cells with scarce pigmentation. This is the first successful inter-species
      study on zebrafish by using blastula cell transplants from rosy barb both
      belonging to the same family cyprinidae.

PMID- 15573537
TI  - Improvement of dry matter digestibility of water hyacinth by solid state
      fermentation using white rot fungi.
AB  - Feeding value of water hyacinth biomass colonized by three species of white rot
      fungi during solid-state fermentation was investigated. All three organisms
      proved to be efficient degraders and enhanced dry matter digestibility. Loss of
      organic matter was maximum (23.6+/-0.1% dry wt) after 48 days by P. ostreatus. C.
      indica showed maximum cellulose degradation (18.5+/-0.1% dry wt) than other two
      fungi after 48 days of incubation. In all cases, an extensive removal of
      hemicellulose at the initial growth period and a delayed degradation of lignin
      were observed. Hemicellulolysis was maximum (46.3+/-0.1% dry wt) by C. indica,
      but delignification (14.2+/-0.2% dry wt) by P. sajor-caju after 48 days. The
      amount of reducing sugar in the degraded biomass decreased at early stages, but
      increased as degradation progressed in all three cases (maximum 1.1+/-0.05% dry
      wt after 48 days by C. indica). Soluble nitrogen content increased only during 16
      32 days of incubation (highest 1.1+/-0.1% dry wt after 32 days by P. sajor-caju).
      Crude protein of the bioconverted biomass increased gradually up to 32 days but
      decreased thereafter (maximum 10.3+/-0.1% dry wt after 32 days by P. sajor -
      caju). Per cent change in in vitro dry matter digestibility of degraded
      substrates enhanced gradually after 8 days and reached maximum after 32 days but
      thereafter decreased (highest + 20.4+/-0.3% dry wt by P. sajor-caju). The results
      demonstrated the efficient degrading capacity of the test fungi and their
      potential use in conversion of water hyacinth biomass into mycoprotein-rich
      ruminant feed, more so by P. sajor-caju.

PMID- 15573538
TI  - Effect of nucleoside-5'-phosphates on collagen-induced in vitro mineralization.
AB  - Nucleoside triphosphates (NTPs) at 4-10 microM concentrations were found to
      inhibit the rates of collagen-induced in vitro mineralization and ion exchange
      reactions. The sequential removal of the terminal phosphate groups caused a step
      wise decrease in their inhibitory potency. The results suggest that NTPs inhibit
      the rates of ion uptake and exchange reactions at concentrations much lower than
      their intracellular physiological concentrations. Thus NTPs may be involved in
      the control of biological mineralization and the tissues which mineralize under
      physiological conditions develop a system to locally convert NTPs to NDPs and
      NMPs.

PMID- 15573539
TI  - Light pen use and practice minimize age and hand performance differences in
      pointing tasks.
AB  - We contrasted performance with mouse and light pen input devices for younger,
      middle-aged, and older adults (N = 72) who were experienced mouse users.
      Participants used both preferred and nonpreferred hands to perform a menu target
      selection task. The light pen minimized age differences in performance relative
      to the mouse. Older adults were more lateralized on a handedness test than young
      adults and were less efficient using their nonpreferred hand. With practice,
      older adults improved their response time more than other age groups did. The
      mouse was rated as more acceptable and easier to use than the light pen across
      trials, despite the performance advantage of the light pen for all age groups.
      Usability ratings correlated moderately with performance. A benefit-cost analysis
      indicated that the more efficient light pen might cover its greater initial cost
      within 11 months for an older adult and within 23 months for a younger adult.
      Actual or potential applications of this research include advising older adults
      to persist with practice for new input devices, advising those who must switch to
      their non-preferred hand to select a direct positioning device, and providing a
      methodology for determining the potential payback interval when switching to a
      faster, though more expensive, input device.

PMID- 15573540
TI  - Age differences in search of web pages: the effects of link size, link number,
      and clutter.
AB  - Reaction time, eye movements, and errors were measured during visual search of
      Web pages to determine age-related differences in performance as a function of
      link size, link number, link location, and clutter. Participants (15 young
      adults, M = 23 years; 14 older adults, M = 57 years) searched Web pages for
      target links that varied from trial to trial. During one half of the trials,
      links were enlarged from 10-point to 12-point font. Target location was
      distributed among the left, center, and bottom portions of the screen. Clutter
      was manipulated according to the percentage of used space, including graphics and
      text, and the number of potentially distracting nontarget links was varied.
      Increased link size improved performance, whereas increased clutter and links
      hampered search, especially for older adults. Results also showed that links
      located in the left region of the page were found most easily. Actual or
      potential applications of this research include Web site design to increase
      usability, particularly for older adults.

PMID- 15573541
TI  - Not Now! Supporting interruption management by indicating the modality and
      urgency of pending tasks.
AB  - Operators in complex event-driven domains must coordinate competing attentional
      demands in the form of multiple tasks and interactions. This study examined the
      extent to which this requirement can be supported more effectively through
      informative interruption cueing (in this case, partial information about the
      nature of pending tasks). The 48 participants performed a visually demanding air
      traffic control (ATC) task. They were randomly assigned to 1 of 3 experimental
      groups that differed in the availability of information (not available, available
      upon request, available automatically) about the urgency and modality of pending
      interruption tasks. Within-subject variables included ATC-related workload and
      the modality, frequency, and priority of interruption tasks. The results show
      that advance knowledge about the nature of pending tasks led participants to
      delay visual interruption tasks the longest, which allowed them to avoid
      intramodal interference and scanning costs associated with performing these tasks
      concurrently with ATC tasks. The 3 experimental groups did not differ
      significantly in terms of their interruption task performance; however, the group
      that automatically received task-related information showed better ATC
      performance, thus experiencing a net performance gain. Actual or potential
      applications of this research include the design of interfaces in support of
      attention and interruption management in a wide range of event-driven
      environments.

PMID- 15573542
TI  - Stimuli fixation and manual response as a function of expectancies.
AB  - Two experiments investigated effects of expectations on eye fixations and
      responses to expected and unexpected information in a laboratory setting.
      Stimulus fixation and manual responses to predefined targets among distractors
      were measured in a dynamic environment shown on a monitor. Participants were part
      of either a predictable condition (predictable sequence of targets and
      distractors) or a random condition. In the predictable condition, participants
      fixated expected distractors less than targets, with similar fixation times in
      the random condition. Responses to targets were faster in the predictable
      condition than in the random condition. Irregularities were either missed or
      responses were slow. This indicates that incorrect expectations may have negative
      consequences, with practical implications for skill-based tasks such as operator
      monitoring and driving. Actual or potential applications of this research include
      introducing operator support for tasks in which the risk of missing unexpected
      information or of slow responses may be dramatic.

PMID- 15573543
TI  - Conversation disrupts change detection in complex traffic scenes.
AB  - A set of studies examined the effects of cognitive distraction on visual scanning
      and change detection in natural traffic scenes. Experiment 1 found that a
      naturalistic hands-free phone conversation could disrupt change detection,
      thereby degrading the encoding of visual information and increasing the frequency
      of undetected changes. Data also revealed a tendency for conversation to impair
      knowledge-driven orienting of attention in older adults. Experiment 2 found that
      an attentive listening task produced no such effects. Actual or potential
      applications of this research include the design of displays and interventions to
      minimize the effects of cognitive distraction on human performance.

PMID- 15573544
TI  - Effect of job rotation on work demands, workload, and recovery of refuse truck
      drivers and collectors.
AB  - Job rotation is often advocated to reduce workload, but its efficacy has seldom
      been investigated. The aim of this study is to compare the work demands,
      workload, and recovery among truck driving, refuse collecting, and rotating
      between these two jobs, between days and during the day. Three teams of 3
      employees each participated in this study. Work demands were assessed by
      systematic observation of tasks and activities. Workload was quantified by means
      of heart rate, oxygen uptake, subjective ratings, and urinary excretion rates of
      catecholamines. Recovery was quantified by excretion rates of catecholamines
      after work. Job rotation between driving and collecting is an effective measure
      to reduce physical workload as compared with collecting only and to decrease
      mental workload as compared with driving only. However, job rotation resulted in
      increased physical workload as compared with driving only. Job rotation did not
      increase mental workload as compared with collecting only. No effects were seen
      on recovery. No differences were found between rotating between days and during
      the day. Actual or potential applications of this research include the
      recommendation that before job rotation is introduced, its efficacy be determined
      in terms of well-chosen workload measures because a reduction in work demands
      does not directly imply a reduction in workload. Therefore, job rotation might be
      less effective than expected.

PMID- 15573545
TI  - Learning to make decisions in dynamic environments: effects of time constraints
      and cognitive abilities.
AB  - This study investigated the effects of time constraints and cognitive abilities
      on dynamic decision making (DDM). The learning and performance of individuals
      trained in a DDM task with time constraints were compared with those who were
      trained without time constraints. Although all participants received the same
      total amount of time to perform the task, individuals under more stringent time
      constraints were given 3 times more practice trials on the first 2 days of the
      study than were people under less stringent time constraints. Despite the
      additional practice runs, participants under high time constraints performed
      worse than did participants under low time constraints on the 3rd day of the
      study. A subsequent analysis of cognitive abilities and decision heuristics
      revealed that individuals' actions corresponded with simple heuristic predictions
      more closely with minimal practice than with extended practice, under high rather
      than low time constraints, and in individuals with low rather than high cognitive
      abilities. These findings suggest that mere repetition of a task with less time
      within a trial is counterproductive to learning and that learning depends on
      cognitive abilities. Potential applications of this research include the design
      of training procedures for dynamic tasks.

PMID- 15573546
TI  - Memory processes of flight situation awareness: interactive roles of working
      memory capacity, long-term working memory, and expertise.
AB  - This research examined the role of working memory (WM) capacity and long-term
      working memory (LT-WM) in flight situation awareness (SA). We developed spatial
      and verbal measures of WM capacity and LT-WM skill and then determined the
      ability of these measures to predict pilot performance on SA tasks. Although both
      spatial measures of WM capacity and LT-WM skills were important predictors of SA
      performance, their importance varied as a function of pilot expertise. Spatial WM
      capacity was most predictive of SA performance for novices, whereas spatial LT-WM
      skill based on configurations of control flight elements (attitude and power) was
      most predictive for experts. Furthermore, evidence for an interactive role of WM
      and LT-WM mechanisms was indicated. Actual or potential applications of this
      research include cognitive analysis of pilot expertise and aviation training.

PMID- 15573547
TI  - Characterizing the effects of droplines on target acquisition performance on a 3
      D perspective display.
AB  - The present study investigated the effects of droplines on target acquisition
      performance on a 3-D perspective display in which participants were required to
      move a cursor into a target cube as quickly as possible. Participants'
      performance and coordination strategies were characterized using both Fitts' law
      and acquisition patterns of the 3 viewer-centered target display dimensions
      (azimuth, elevation, and range). Participants' movement trajectories were
      recorded and used to determine movement times for acquisitions of the entire
      target and of each of its display dimensions. The goodness of fit of the data to
      a modified Fitts function varied widely among participants, and the presence of
      droplines did not have observable impacts on the goodness of fit. However,
      droplines helped participants navigate via straighter paths and particularly
      benefited range dimension acquisition. A general preference for visually
      overlapping the target with the cursor prior to capturing the target was found.
      Potential applications of this research include the design of interactive 3-D
      perspective displays in which fast and accurate selection and manipulation of
      content residing at multiple ranges may be a challenge.

PMID- 15573548
TI  - Sonification supports eyes-free respiratory monitoring and task time-sharing.
AB  - Three experiments explored the effectiveness of continuous auditory displays, or
      sonifications, for conveying information about a simulated anesthetized patient's
      respiration. Experiment 1 established an effective respiratory sonification.
      Experiment 2 showed an effect of expertise in the use of respiratory sonification
      and revealed that some apparent differences in sonification effectiveness could
      be accounted for by response bias. Experiment 3 showed that sonification helps
      anesthesiologists to maintain high levels of awareness of the simulated patient's
      state while performing other tasks more effectively than when relying upon visual
      monitoring of the simulated patient state. Overall, sonification of patient
      physiology beyond traditional pulse oximetry appears to be a viable and useful
      adjunct to visual monitors. Actual and potential applications of this research
      include monitoring in a wide variety of busy critical care contexts.

PMID- 15573549
TI  - Speed-accuracy characteristics of human-machine cooperative manipulation using
      virtual fixtures with variable admittance.
AB  - This work explores the effect of virtual fixture admittance on the performance,
      defined by error and time, of task execution with a human-machine cooperative
      system. A desired path is obtained using computer vision, and virtual fixtures
      for assistance in planar path following were implemented on an admittance
      controlled robot. The admittance controller uses a velocity gain, so that the
      speed of the robot is proportional to the force applied by the operator. The
      level of virtual fixture guidance is determined by the admittance ratio, which is
      the ratio of the admittance gain of the force components orthogonal to the path
      to the gain of the force components parallel to the path. In Experiment 1, we
      found a linear relationship between admittance ratio and performance. In
      Experiment 2, we examined the effect of admittance ratio on the performance of
      three tasks: path following, off-path targeting, and obstacle avoidance. An
      algorithm was developed to select an appropriate admittance ratio based on the
      nature of the task. Automatic admittance ratio tuning is recommended for next
      generation virtual fixtures. Actual or potential applications of this research
      include surgery, assembly, and manipulation at the macro and micro scales.

PMID- 15573550
TI  - A new model of scheduling in manufacturing: tasks, roles, and monitoring.
AB  - For over 3 decades there was a belief that computer-based solutions would "solve"
      complex industrial scheduling problems, yet most manufacturing organizations
      still require human contributions for effective scheduling performance. We
      present a new model of scheduling for the development and implementation of
      effective scheduling systems within manufacturing companies. The model derives
      from investigating the work of 7 schedulers in 4 manufacturing environments using
      a qualitative field study approach, for which novel field-based data collection
      and analysis methods were developed. The results show that scheduling in practice
      comprises task, role, and monitoring activities and that the business environment
      influences a scheduler at work. A new definition of scheduling is presented that
      includes the significant facilitation and implementation aspects of human
      scheduling ignored by many computer-based scheduling approaches. The implications
      for this model extend across the domains of human factors and operations
      management, especially for the analysis and improvement of existing and new
      production planning and control processes and enterprise information systems.
      Actual or potential applications of this research include the analysis, design,
      and management of planning, scheduling, and control processes in industry; the
      selection, training, and support of production schedulers; and the allocation of
      tasks to humans and computer systems in industrial planning, scheduling, and
      control processes.

PMID- 15573551
TI  - Partitioning visual displays aids task-directed visual search.
AB  - We reduced time to detect target symbols in mock radar screens by adding
      perceptual boundaries that partitioned displays in accordance with task
      instructions. Targets appeared among distractor symbols either close to or far
      from the display center, and participants were instructed to find the target
      closest to the center. Search time increased with both number of distractors and
      distance of target from center. However, when close and far regions were
      delineated by a centrally presented "range ring," the distractor effect was
      substantially reduced. In addition, eye movement patterns more closely resembled
      a task-efficient spiral when displays contained a range ring. Results suggest
      that the addition of perceptual boundaries to visual displays can help to guide
      search in accordance with task-directed constraints. Actual or potential
      applications of this research include the incorporation of perceptual boundaries
      into display designs in order to encourage task-efficient scanpaths (as
      identified via task analysis and/or empirical testing).

PMID- 15573552
TI  - When redundant on-screen text in multimedia technical instruction can interfere
      with learning.
AB  - It is frequently assumed that presenting the same material in written and spoken
      form benefits learning and understanding. The present work provides a theoretical
      justification based on cognitive load theory, and empirical evidence based on
      controlled experiments, that this assumption can be incorrect. From a theoretical
      perspective, it is suggested that if learners are required to coordinate and
      simultaneously process redundant material such as written and spoken text, an
      excessive working memory load is generated. Three experiments involving a group
      of 25 technical apprentices compared the effects of simultaneously presenting the
      same written and auditory textual information as opposed to either temporally
      separating the two modes or eliminating one of the modes. The first two
      experiments demonstrated that nonconcurrent presentation of auditory and visual
      explanations of a diagram proved superior, in terms of ratings of mental load and
      test scores, to a concurrent presentation of the same explanations when
      instruction time was constrained. The 3rd experiment demonstrated that a
      concurrent presentation of identical auditory and visual technical text (without
      the presence of diagrams) was significantly less efficient in comparison with an
      auditory-only text. Actual or potential applications of this research include the
      design and evaluation of multimedia instructional systems and audiovisual
      displays.

PMID- 15573553
TI  - We're getting the message about drugs.

PMID- 15573554
TI  - Claims management as a key to your safety program.

PMID- 15573555
TI  - Depicting the scene: new software quickly creates accurate, courtroom-ready maps.

PMID- 15573556
TI  - Danger overhead.

PMID- 15573557
TI  - A business case for sustainability.

PMID- 15573558
TI  - Innovative uses of thermal imaging.

PMID- 15573559
TI  - Finding the right approach. What do you mean, this is a non-permit required
      confined space?
AB  - While not a big fan of the non-permit confined space designation, I have come to
      believe the approach can work if done properly. However, it is this author's
      opinion that the designation of a confined space as non-permit required in any
      work environment should be the exception rather than the rule. The up-front
      determination that a space is "non-permit-required" should necessarily consume
      more time and resources than assuming the space is "permit-required" because so
      fewer controls are in place. Most certainly, this decision must be based on the
      knowledge that no hazards are present or have the potential to develop, rather
      than on "convenience" or "resource limitations"; assumptions should never play a
      part in the decision. Attention to proper evaluation of confined spaces,
      documentation of actual conditions over time, and communication to those entering
      the spaces are all critical components of a safe confined space entry program,
      whether the space be permit-required or not.

PMID- 15573560
TI  - 'Power' tools for your program.

PMID- 15573561
TI  - The REDON alternative.

PMID- 15573562
TI  - Predicting the effect of high RH on organic vapor cartridge performance.

PMID- 15573563
TI  - Options in driver training.

PMID- 15573564
TI  - International influence. Will the Z87.1 Committee take an entirely new approach
      when the eye and face protection standard is revised in 2008?

PMID- 15573565
TI  - You'd better watch out. Colder weather moves hypothermia and slip-and-fall
      prevention to the top of many work sites' hazards list.

PMID- 15573566
TI  - Key findings and extended summaries.

PMID- 15573567
TI  - Rationale, concepts and approach to the assessment.

PMID- 15573568
TI  - Past changes in Arctic terrestrial ecosystems, climate and UV radiation.
AB  - At the last glacial maximum, vast ice sheets covered many continental areas. The
      beds of some shallow seas were exposed thereby connecting previously separated
      landmasses. Although some areas were ice-free and supported a flora and fauna,
      mean annual temperatures were 10-13 degrees C colder than during the Holocene.
      Within a few millennia of the glacial maximum, deglaciation started,
      characterized by a series of climatic fluctuations between about 18,000 and
      11,400 years ago. Following the general thermal maximum in the Holocene, there
      has been a modest overall cooling trend, superimposed upon which have been a
      series of millennial and centennial fluctuations in climate such as the "Little
      Ice Age spanning approximately the late 13th to early 19th centuries. Throughout
      the climatic fluctuations of the last 150,000 years, Arctic ecosystems and biota
      have been close to their minimum extent within the most recent 10,000 years. They
      suffered loss of diversity as a result of extinctions during the most recent
      large-magnitude rapid global warming at the end of the last glacial stage.
      Consequently, Arctic ecosystems and biota such as large vertebrates are already
      under pressure and are particularly vulnerable to current and projected future
      global warming. Evidence from the past indicates that the treeline will very
      probably advance, perhaps rapidly, into tundra areas, as it did during the early
      Holocene, reducing the extent of tundra and increasing the risk of species
      extinction. Species will very probably extend their ranges northwards, displacing
      Arctic species as in the past. However, unlike the early Holocene, when lower
      relative sea level allowed a belt of tundra to persist around at least some parts
      of the Arctic basin when treelines advanced to the present coast, sea level is
      very likely to rise in future, further restricting the area of tundra and other
      treeless Arctic ecosystems. The negative response of current Arctic ecosystems to
      global climatic conditions that are apparently without precedent during the
      Pleistocene is likely to be considerable, particularly as their exposure to co
      occurring environmental changes (such as enhanced levels of UV-B, deposition of
      nitrogen compounds from the atmosphere, heavy metal and acidic pollution,
      radioactive contamination, increased habitat fragmentation) is also without
      precedent.

PMID- 15573569
TI  - Biodiversity, distributions and adaptations of Arctic species in the context of
      environmental change.
AB  - The individual of a species is the basic unit which responds to climate and UV-B
      changes, and it responds over a wide range of time scales. The diversity of
      animal, plant and microbial species appears to be low in the Arctic, and
      decreases from the boreal forests to the polar deserts of the extreme North but
      primitive species are particularly abundant. This latitudinal decline is
      associated with an increase in super-dominant species that occupy a wide range of
      habitats. Climate warming is expected to reduce the abundance and restrict the
      ranges of such species and to affect species at their northern range boundaries
      more than in the South: some Arctic animal and plant specialists could face
      extinction. Species most likely to expand into tundra are boreal species that
      currently exist as outlier populations in the Arctic. Many plant species have
      characteristics that allow them to survive short snow-free growing seasons, low
      solar angles, permafrost and low soil temperatures, low nutrient availability and
      physical disturbance. Many of these characteristics are likely to limit species'
      responses to climate warming, but mainly because of poor competitive ability
      compared with potential immigrant species. Terrestrial Arctic animals possess
      many adaptations that enable them to persist under a wide range of temperatures
      in the Arctic. Many escape unfavorable weather and resource shortage by winter
      dormancy or by migration. The biotic environment of Arctic animal species is
      relatively simple with few enemies, competitors, diseases, parasites and
      available food resources. Terrestrial Arctic animals are likely to be most
      vulnerable to warmer and drier summers, climatic changes that interfere with
      migration routes and staging areas, altered snow conditions and freeze-thaw
      cycles in winter, climate-induced disruption of the seasonal timing of
      reproduction and development, and influx of new competitors, predators, parasites
      and diseases. Arctic microorganisms are also well adapted to the Arctic's
      climate: some can metabolize at temperatures down to -39 degrees C. Cyanobacteria
      and algae have a wide range of adaptive strategies that allow them to avoid, or
      at least minimize UV injury. Microorganisms can tolerate most environmental
      conditions and they have short generation times which can facilitate rapid
      adaptation to new environments. In contrast, Arctic plant and animal species are
      very likely to change their distributions rather than evolve significantly in
      response to warming.

PMID- 15573570
TI  - Responses to projected changes in climate and UV-B at the species level.
AB  - Environmental manipulation experiments showed that species respond
      individualistically to each environmental-change variable. The greatest responses
      of plants were generally to nutrient, particularly nitrogen, addition. Summer
      warming experiments showed that woody plant responses were dominant and that
      mosses and lichens became less abundant. Responses to warming were controlled by
      moisture availability and snow cover. Many invertebrates increased population
      growth in response to summer warming, as long as desiccation was not induced. CO2
      and UV-B enrichment experiments showed that plant and animal responses were
      small. However, some microorganisms and species of fungi were sensitive to
      increased UV-B and some intensive mutagenic actions could, perhaps, lead to
      unexpected epidemic outbreaks. Tundra soil heating, CO2 enrichment and amendment
      with mineral nutrients generally accelerated microbial activity. Algae are likely
      to dominate cyanobacteria in milder climates. Expected increases in winter freeze
      thaw cycles leading to ice-crust formation are likely to severely reduce winter
      survival rate and disrupt the population dynamics of many terrestrial animals. A
      deeper snow cover is likely to restrict access to winter pastures by
      reindeer/caribou and their ability to flee from predators while any earlier onset
      of the snow-free period is likely to stimulate increased plant growth. Initial
      species responses to climate change might occur at the sub-species level: an
      Arctic plant or animal species with high genetic/racial diversity has proved an
      ability to adapt to different environmental conditions in the past and is likely
      to do so also in the future. Indigenous knowledge, air photographs, satellite
      images and monitoring show that changes in the distributions of some species are
      already occurring: Arctic vegetation is becoming more shrubby and more
      productive, there have been recent changes in the ranges of caribou, and "new"
      species of insects and birds previously associated with areas south of the
      treeline have been recorded. In contrast, almost all Arctic breeding bird species
      are declining and models predict further quite dramatic reductions of the
      populations of tundra birds due to warming. Species-climate response surface
      models predict potential future ranges of current Arctic species that are often
      markedly reduced and displaced northwards in response to warming. In contrast,
      invertebrates and microorganisms are very likely to quickly expand their ranges
      northwards into the Arctic.

PMID- 15573571
TI  - Effects on the structure of Arctic ecosystems in the short- and long-term
      perspectives.
AB  - Species individualistic responses to warming and increased UV-B radiation are
      moderated by the responses of neighbors within communities, and trophic
      interactions within ecosystems. All of these responses lead to changes in
      ecosystem structure. Experimental manipulation of environmental factors expected
      to change at high latitudes showed that summer warming of tundra vegetation has
      generally led to smaller changes than fertilizer addition. Some of the factors
      manipulated have strong effects on the structure of Arctic ecosystems but the
      effects vary regionally, with the greatest response of plant and invertebrate
      communities being observed at the coldest locations. Arctic invertebrate
      communities are very likely to respond rapidly to warming whereas microbial
      biomass and nutrient stocks are more stable. Experimentally enhanced UV-B
      radiation altered the community composition of gram-negative bacteria and fungi,
      but not that of plants. Increased plant productivity due to warmer summers may
      dominate food-web dynamics. Trophic interactions of tundra and sub-Arctic forest
      plant-based food webs are centered on a few dominant animal species which often
      have cyclic population fluctuations that lead to extremely high peak abundances
      in some years. Population cycles of small rodents and insect defoliators such as
      the autumn moth affect the structure and diversity of tundra and forest-tundra
      vegetation and the viability of a number of specialist predators and parasites.
      Ice crusting in warmer winters is likely to reduce the accessibility of plant
      food to lemmings, while deep snow may protect them from snow-surface predators.
      In Fennoscandia, there is evidence already for a pronounced shift in small rodent
      community structure and dynamics that have resulted in a decline of predators
      that specialize in feeding on small rodents. Climate is also likely to alter the
      role of insect pests in the birch forest system: warmer winters may increase
      survival of eggs and expand the range of the insects. Insects that harass
      reindeer in the summer are also likely to become more widespread, abundant and
      active during warmer summers while refuges for reindeer/caribou on glaciers and
      late snow patches will probably disappear.

PMID- 15573572
TI  - Effects on the function of Arctic ecosystems in the short- and long-term
      perspectives.
AB  - Historically, the function of Arctic ecosystems in terms of cycles of nutrients
      and carbon has led to low levels of primary production and exchanges of energy,
      water and greenhouse gases have led to low local and regional cooling.
      Sequestration of carbon from atmospheric CO2, in extensive, cold organic soils
      and the high albedo from low, snow-covered vegetation have had impacts on
      regional climate. However, many aspects of the functioning of Arctic ecosystems
      are sensitive to changes in climate and its impacts on biodiversity. The current
      Arctic climate results in slow rates of organic matter decomposition. Arctic
      ecosystems therefore tend to accumulate organic matter and elements despite low
      inputs. As a result, soil-available elements like nitrogen and phosphorus are key
      limitations to increases in carbon fixation and further biomass and organic
      matter accumulation. Climate warming is expected to increase carbon and element
      turnover, particularly in soils, which may lead to initial losses of elements but
      eventual, slow recovery. Individual species and species diversity have clear
      impacts on element inputs and retention in Arctic ecosystems. Effects of
      increased CO2 and UV-B on whole ecosystems, on the other hand, are likely to be
      small although effects on plant tissue chemisty, decomposition and nitrogen
      fixation may become important in the long-term. Cycling of carbon in trace gas
      form is mainly as CO2 and CH4. Most carbon loss is in the form of CO2, produced
      by both plants and soil biota. Carbon emissions as methane from wet and moist
      tundra ecosystems are about 5% of emissions as CO2 and are responsive to warming
      in the absence of any other changes. Winter processes and vegetation type also
      affect CH4 emissions as well as exchanges of energy between biosphere and
      atmosphere. Arctic ecosystems exhibit the largest seasonal changes in energy
      exchange of any terrestrial ecosystem because of the large changes in albedo from
      late winter, when snow reflects most incoming radiation, to summer when the
      ecosystem absorbs most incoming radiation. Vegetation profoundly influences the
      water and energy exchange of Arctic ecosystems. Albedo during the period of snow
      cover declines from tundra to forest tundra to deciduous forest to evergreen
      forest. Shrubs and trees increase snow depth which in turn increases winter soil
      temperatures. Future changes in vegetation driven by climate change are
      therefore, very likely to profoundly alter regional climate.

PMID- 15573573
TI  - Effects of changes in climate on landscape and regional processes, and feedbacks
      to the climate system.
AB  - Biological and physical processes in the Arctic system operate at various
      temporal and spatial scales to impact large-scale feedbacks and interactions with
      the earth system. There are four main potential feedback mechanisms between the
      impacts of climate change on the Arctic and the global climate system: albedo,
      greenhouse gas emissions or uptake by ecosystems, greenhouse gas emissions from
      methane hydrates, and increased freshwater fluxes that could affect the
      thermohaline circulation. All these feedbacks are controlled to some extent by
      changes in ecosystem distribution and character and particularly by large-scale
      movement of vegetation zones. Indications from a few, full annual measurements of
      CO2 fluxes are that currently the source areas exceed sink areas in geographical
      distribution. The little available information on CH4 sources indicates that
      emissions at the landscape level are of great importance for the total greenhouse
      balance of the circumpolar North. Energy and water balances of Arctic landscapes
      are also important feedback mechanisms in a changing climate. Increasing density
      and spatial expansion of vegetation will cause a lowering of the albedo and more
      energy to be absorbed on the ground. This effect is likely to exceed the negative
      feedback of increased C sequestration in greater primary productivity resulting
      from the displacements of areas of polar desert by tundra, and areas of tundra by
      forest. The degradation of permafrost has complex consequences for trace gas
      dynamics. In areas of discontinuous permafrost, warming, will lead to a complete
      loss of the permafrost. Depending on local hydrological conditions this may in
      turn lead to a wetting or drying of the environment with subsequent implications
      for greenhouse gas fluxes. Overall, the complex interactions between processes
      contributing to feedbacks, variability over time and space in these processes,
      and insufficient data have generated considerable uncertainties in estimating the
      net effects of climate change on terrestrial feedbacks to the climate system.
      This uncertainty applies to magnitude, and even direction of some of the
      feedbacks.

PMID- 15573574
TI  - Synthesis of effects in four Arctic subregions.
AB  - An assessment of impacts on Arctic terrestrial ecosystems has emphasized
      geographical variability in responses of species and ecosystems to environmental
      change. This variability is usually associated with north-south gradients in
      climate, biodiversity, vegetation zones, and ecosystem structure and function. It
      is clear, however, that significant east-west variability in environment,
      ecosystem structure and function, environmental history, and recent climate
      variability is also important. Some areas have cooled while others have become
      warmer. Also, east-west differences between geographical barriers of oceans,
      archipelagos and mountains have contributed significantly in the past to the
      ability of species and vegetation zones to relocate in response to climate
      changes, and they have created the isolation necessary for genetic
      differentiation of populations and biodiversity hot-spots to occur. These
      barriers will also affect the ability of species to relocate during projected
      future warming. To include this east-west variability and also to strike a
      balance between overgeneralization and overspecialization, the ACIA identified
      four major sub regions based on large-scale differences in weather and climate
      shaping factors. Drawing on information, mostly model output that can be related
      to the four ACIA subregions, it is evident that geographical barriers to species
      re-location, particularly the distribution of landmasses and separation by seas,
      will affect the northwards shift in vegetation zones. The geographical
      constraints--or facilitation--of northward movement of vegetation zones will
      affect the future storage and release of carbon, and the exchange of energy and
      water between biosphere and atmosphere. In addition, differences in the ability
      of vegetation zones to re-locate will affect the biodiversity associated with
      each zone while the number of species threatened by climate change varies greatly
      between subregions with a significant hot-spot in Beringia. Overall, the
      subregional synthesis demonstrates the difficulty of generalizing projections of
      responses of ecosystem structure and function, species loss, and biospheric
      feedbacks to the climate system for the whole Arctic region and implies a need
      for a far greater understanding of the spatial variability in the responses of
      terrestrial arctic ecosystems to climate change.

PMID- 15573575
TI  - Uncertainties and recommendations.
AB  - An assessment of the impacts of changes in climate and UV-B radiation on Arctic
      terrestrial ecosystems, made within the Arctic Climate Impacts Assessment (ACIA),
      highlighted the profound implications of projected warming in particular for
      future ecosystem services, biodiversity and feedbacks to climate. However,
      although our current understanding of ecological processes and changes driven by
      climate and UV-B is strong in some geographical areas and in some disciplines, it
      is weak in others. Even though recently the strength of our predictions has
      increased dramatically with increased research effort in the Arctic and the
      introduction of new technologies, our current understanding is still constrained
      by various uncertainties. The assessment is based on a range of approaches that
      each have uncertainties, and on data sets that are often far from complete.
      Uncertainties arise from methodologies and conceptual frameworks, from
      unpredictable surprises, from lack of validation of models, and from the use of
      particular scenarios, rather than predictions, of future greenhouse gas emissions
      and climates. Recommendations to reduce the uncertainties are wide-ranging and
      relate to all disciplines within the assessment. However, a repeated theme is the
      critical importance of achieving an adequate spatial and long-term coverage of
      experiments, observations and monitoring of environmental changes and their
      impacts throughout the sparsely populated and remote region that is the Arctic.

PMID- 15573576
TI  - Arctic climate change and its impacts.

PMID- 15573577
TI  - Calculating computing's environmental cost.

PMID- 15573578
TI  - Walter J. Weber, Jr.'s Unique Legacy.

PMID- 15573579
TI  - Modeling trichloroethylene adsorption by activated carbon preloaded with natural
      dissolved organic matter using a modified IAST approach.
AB  - A model was developed, using an approach based on the Ideal Adsorbed Solution
      Theory (IAST), to predict trichloroethylene (TCE) adsorption by granular
      activated carbon (GAC) preloaded with natural dissolved organic matter (DOM)
      isolated from three surface water sources. The IAST model was formulated for a bi
      solute system in which TCE and DOM single-solute uptakes were described by the
      Langmuir-Freundlich and Freundlich isotherms, respectively. The effect of DOM
      molecular size and polarity (as measured by XAD 8 resin fractionation) on TCE
      uptake by preloaded GAC was assessed to identify a reactive fraction of natural
      water DOM for the purpose of modeling competitive adsorption. Consistent with
      previous work that identified low molecular weight species as the most reactive
      with regard to preloading effects (i.e., reducing target compound uptake), the
      low molecular weight components of the polar (hydrophilic) and nonpolar
      (hydrophobic) DOM fractions, isolated using ultrafiltration (1 kDa molecular
      weight cutoff membrane), exhibited significant competitive effects. Furthermore,
      the effects of these fractions on TCE uptake were similar; therefore, theywere
      considered together to represent a single "reactive fraction" of DOM. On the
      basis of this finding, isotherms for the <1 kDa low molecular weight DOM fraction
      of the whole water were measured, and molar concentrations were computed based on
      an average molecular weight determined using size-exclusion chromatography. The
      IAST model was modified to incorporate surface area reduction due to pore
      blockage by DOM and to reflectthe hypothesis thatTCE molecules can access
      adsorption sites which humic molecules cannot, thus preventing competition on
      these sites. The model was calibrated with data for TCE uptake by carbon
      preloaded with the <1 kDa low molecular weight DOM fraction and was verified by
      predicting TCE uptake by carbon preloaded with whole natural waters for both
      constant GAC dose (hence constant DOM loading) and variable GAC dose (hence
      variable DOM loading) TCE isotherms. Preloading by DOM reduced volume in GAC
      pores having widths smaller than 1.25 nm (likely accessible only to TCE) to a
      greater extent than total pore volume, suggesting preferential blockage of
      micropores. Such preferential pore blockage may explain, in part, why increased
      DOM loading decreases the fraction of the total surface area on which no
      competition between TCE and DOM occurs.

PMID- 15573580
TI  - Trichloroethylene adsorption by fibrous and granular activated carbons: aqueous
      phase, gas phase, and water vapor adsorption studies.
AB  - The important adsorption components involved in the removal of trichloroethylene
      (TCE) by fibrous and granular activated carbons from aqueous solutions were
      systematically examined. Namely, adsorption of TCE itself (i.e., TCE vapor
      isotherms), water molecules (i.e., water vapor isotherms), and TCE in water
      (i.e., TCE aqueous phase isotherms) were studied, side-by-side, using 20 well
      characterized surface-modified activated carbons. The results showed that TCE
      molecular size and geometry, activated carbon surface hydrophilicity, pore
      volume, and pore size distribution in micropores control adsorption of TCE at
      relatively dilute aqueous solutions. TCE adsorption increased as the carbon
      surface hydrophilicity decreased and the pore volume in micropores of less than
      10 A, especially in the 5-8 A range, increased. TCE molecules appeared to access
      deep regions of carbon micropores due to their flat geometry. The results
      indicated that characteristics of both adsorbate (i.e., the molecular structure,
      size, and geometry) and activated carbon (surface hydrophilicity, pore volume,
      and pore size distribution of micropores) control adsorption of synthetic organic
      compounds from water and wastewaters. The important micropore size region for a
      target compound adsorption depends on its size and geometry.

PMID- 15573581
TI  - Black carbon and kerogen in soils and sediments. 2. Their roles in equilibrium
      sorption of less-polar organic pollutants.
AB  - The first paper of this series reported that soil/sediment organic matter (SOM)
      can be fractionated into four fractions with a combined wet chemical procedure
      and that kerogen and black carbon (BC) are major SOM components in soil/sediment
      samples collected from the industrialized suburban areas of Guangzhou, China. The
      goal of this study was to determine the sorptive properties forthe four SOM
      fractions for organic contaminants. Sorption isotherms were measured with a batch
      technique using phenanthrene and naphthalene as the sorbates and four original
      and four Soxhlet-extracted soil/sediment samples, 15 isolated SOM fractions, and
      a char as the sorbents. The results showed that the sorption isotherms measured
      for all the sorbents were variously nonlinear. The isolated humic acid (HA)
      exhibited significantly nonlinear sorption, but its contribution to the overall
      isotherm nonlinearity and sorption capacity of the original soil was
      insignificant because of its low content in the tested soils and sediments. The
      particulate kerogen and black carbon (KB) fractions exhibited more nonlinear
      sorption with much higher organic carbon-normalized capacities for both sorbates.
      They dominate the observed overall sorption by the tested soils and sediments and
      are expected to be the most important soil components affecting bioavailability
      and ultimate fate of hydrophobic organic contaminants (HOCs). The fact that the
      isolated KB fractions exhibited much higher sorption capacities than when they
      were associated with soil/sediment matrixes suggested that a large fraction of
      the particulate kerogen and BC was not accessible to sorbing HOCs. Encapsulation
      within soil aggregates and surface coverage by inorganic and organic coatings may
      have caused large variations in the accessibility of fine kerogen and BC
      particles to HOCs and hence lowered the sorption capacity of the soil. This
      variability posts an ultimate challenge for precisely predicting HOC sorption by
      soils from the contents of different types of SOM.

PMID- 15573582
TI  - History-dependent sorption in humic acids and a lignite in the context of a
      polymer model for natural organic matter.
AB  - We examined sorption of two apolar compounds in three samples of macromolecular
      natural organic matter (NOM) in order to test whether history-dependent
      ("irreversible") behaviors, including sorption hysteresis and the conditioning
      effect, agree with a pore deformation/creation hypothesis applicable to the
      glassy organic solid state as proposed in the polymer literature. The compounds
      are 1,2,4-trichlorobenzene (TCB) and naphthalene (Naph). The NOM samples are a
      soil humic acid (H-HA), an Al3+-exchanged form of the same humic acid (Al-HA),
      and a low-rank coal (Beulah-Zap lignite, BZL). The HAs, at least, are believed
      free of environmental black carbon. The degree of nonlinearity in the isotherm
      and the ratio of hole-filling to solid-phase dissolution increased in the order
      of hardness (stiffness) of the solid: H-HA < Al-HA < BZL. Independent of solid,
      solutes show a 14-18 kJ/mol preference for hole "sites" as compared to
      dissolution "sites", which we attribute to the free energy needed in the
      dissolution domain to create a cavity to accommodate the solute. All solids
      exhibited hysteresis and the conditioning effect, which refers to enhanced re
      sorption after pretreatment with a conditioning agent (in this case,
      chlorobenzene). Conditioning the sample results in increased sorption and
      increased contribution of hole-filling relative to dissolution. The effects of
      original hole population, matrix stiffness, and solute concentration on the
      hysteresis index and on the magnitude of the conditioning effect are consistent
      with a pore-deformation mechanism as the underlying cause of sorption
      irreversibility. This mechanism involves concurrent processes of irreversible
      hole expansion and the creation of new holes by the incoming sorbate (or
      conditioning agent). The results show that nonlinear and irreversible behavior
      may be expected for macromolecular forms of NOM that are in a glassy state and
      emphasize the case that NOM is not a passive sorbent but may be physically
      altered by the sorbate.

PMID- 15573583
TI  - Effects of competitor and natural organic matter characteristics on the
      equilibrium sorption of 1,2-dichlorobenzene in soil and shale.
AB  - The competitive sorption behaviors of 1,2-DCB in binary solute systems in four
      natural sorbents having natural organic matter (NOM) matrixes of different
      physicochemical characters were investigated in batch reactors. Specifically, the
      study focused on investigating how the extent of 1,2-DCB competitive sorption
      depends on (i) the rigidity of NOM matrixes as assessed by the efficiency of
      chemical oxidation and (ii) the closeness of competitor structure to that of the
      primary solute. The chemical oxidation and elemental composition results suggest
      that the shale NOM is the most reduced and condensed, the peat was the most
      oxidized and amorphous, and two surface soils had intermediate NOM structures.
      Four chlorinated benzenes and phenanthrene were used as competing solutes. All
      five chemicals exhibited competition against 1,2-DCB in all sorbents, including
      the peat, but the extent of competition varied significantly. Little difference
      in the extent of competition with 1,2-DCB was observed for the various
      chlorinated benzenes even though some were liquids and some were solids at the
      experimental temperature. All of the chlorobenzenes were more effective
      competitors than phenanthrene. The shale showed markedly different competition
      features from the other sorbents, with a much smaller competitive effect at a
      given sorbed volume of competitor. However, normalizing sorbed competitor volumes
      by the capacity of the adsorption domain in the Polanyi-Manes single-solute
      partition-adsorption model (V0) produced qualitatively similar competitive
      behavior for each solute; displacement of 1,2-DCB increased with increasing
      sorbed competitor volumes up to V0, and little additional competition occurred
      beyond that point. The extent of competition was positively correlated with the
      maximum adsorption capacity and the fraction of "hard" and "soot" carbon contents
      as assessed by chemical and thermal oxidation methods. These findings indicate
      that competition is associated with voids in the NOM structure, that these voids
      are likely present within the condensed ("hard" plus "soot") carbon domain, and
      therefore that diagenetic alteration of NOM plays a central role in determining
      competitive sorption characteristics for hydrophobic contaminants.

PMID- 15573584
TI  - Influence of humic substance adsorptive fractionation on pyrene partitioning to
      dissolved and mineral-associated humic substances.
AB  - Changes in pyrene binding by dissolved and mineral-associated humic substances
      (HS) due to HS adsorptive fractionation processes were examined in model
      environmental systems using purified Aldrich humic acid (PAHA) and Suwannee River
      fulvic acid (SRFA). For PAHA, carbon-normalized pyrene binding coefficients for
      nonadsorbed, residual fractions (Koc(res)) were different from the original
      dissolved PAHA Koc value (Koc(orig)) prior to contact with the mineral
      suspensions. A strong positive correlation between pyrene log Koc(res) and log
      weight-average molecular weight (MWw) for residual PAHA fractions was observed,
      which was relatively independent of the specific mineral adsorbent used and
      hypothesized fractionation processes. A strong positive correlation between log
      Koc(ads) and log MWw was also found for PAHA fractions adsorbed to kaolinite at
      low mass fraction organic carbon levels, although the relationship was
      statistically different from the one found with residual PAHA fractions. The same
      trends and correlations found for PAHA were not observed with SRFA, suggesting
      that the impacts of HS adsorptive fractionation on changes in hydrophobic organic
      contaminants binding are also influenced by the source and other biogeochemical
      characteristics of HS.

PMID- 15573585
TI  - Selective solubilization of polycyclic aromatic hydrocarbons from multicomponent
      nonaqueous-phase liquids into nonionic surfactant micelles.
AB  - This research investigates the equilibrium solubilization behavior of naphthalene
      and phenanthrene from multicomponent nonaqueous-phase liquids (NAPLs) by five
      different polyoxyethylene nonionic surfactants. The overall goal of the study was
      to achieve an improved understanding of surfactant-aided dissolution of
      polycyclic aromatic hydrocarbons (PAHs) from multicomponent NAPLs in the context
      of surfactant-enhanced remediation of contaminated sites. The extent of
      solubilization of the PAHs in the surfactant micelles increased linearly with the
      PAH mole fraction in the NAPL. The solubilization extent and micelle-water
      equilibrium partition coefficient of the PAHs increased with the size of the
      polar shell region of the micelles rather than the size of the hydrophobic core
      of the micelle. The presence of both PAHs in the shell region of the micelles was
      confirmed by 1H NMR analysis. This is an important observation because it is
      commonly assumed that in multi-solute systems the solutes with relatively greater
      hydrophobicity are solubilized only in the micellar core. A comparison of the 1H
      NMR spectra of pure surfactant solutions and solutions contacted with various
      NAPLs demonstrated that the distribution of PAHs between the shell and the core
      changed with the concentration of PAHs in the micelles and in the NAPL.
      Competitive solubilization of the PAHs was observed when both PAHs were present
      in the NAPL. For example, in surfactant solutions of Brij 35 and Tween 80, the
      solubilization of phenanthrene was decreased in the presence of naphthalene as
      compared to systems that contained phenanthrene as the only solute. In contrast,
      with micellar solutions of Tergitol NP-10 and Triton X-100, phenanthrene
      solubilization was enhanced in the presence of naphthalene. The activity
      coefficients of the PAHs in the micellar phase were generally found to increase
      with PAH concentrations in the micelle.

PMID- 15573586
TI  - Photosensitized degradation of bisphenol A by dissolved organic matter.
AB  - The direct and indirect photolysis of bisphenol A (BPA) was investigated using a
      solar simulator in the absence and presence of dissolved organic matter (DOM).
      BPA degradation by direct photolysis was significantly slower than its rate in
      the presence of DOM. In natural waters, the direct photolytic pathway would be
      even less important due to light screening effects. Surprisingly, differences in
      the rate of indirect BPA photolysis were relatively small between DOM samples.
      Two of the DOM samples represented terrestrial (Suwannee River fulvic acid) and
      autochthonous (Lake Fryxell) geochemical endmembers. The third DOM (Fulton
      County, Ohio) was derived from a temperate artificial wetland. We were unable to
      correlate BPA photoreactivity to the structural components of DOM or its
      extinction coefficient at 280 nm. The addition of methanol, a hydroxyl radical
      scavenger, to reaction solutions slowed but did not completely quench the
      indirect photolysis of BPA. This observation suggests that BPA photodegrades via
      multiple pathways involving other transients formed by the photolysis of DOM.
      Competitive experiments using 2,4,6-trimethylphenol also reduce the reaction rate
      of BPA by DOM and implythat other DOM-derived phototransients (e.g., excited
      triplet state DOM) are involved in the reaction. The reaction rate coefficients
      reported under solar-simulated irradiance in the presence of DOM are
      significantly faster than those reported for the microbial degradation of BPA.
      Thus, in natural surface waters photosensitized transformation of BPA by
      dissolved organic matter may be as important as biodegradation.

PMID- 15573587
TI  - Examination of Darcys law for flow in porous media with variable porosity.
AB  - Henry Darcy's experimental studies in 1856 of saturated water flowthrough a
      homogeneous porous medium contained in a vertical column have provided the basis
      for the quantitative description of fluid flow in a wide variety of both natural
      and engineered porous medium environmental systems. Extrapolation of Darcy's
      original observations and conclusions has led to several commonly applied
      equations used to model flow in porous media. This work examines this original
      experimental study, summarizes the appropriate mathematical expressions that
      ensue directly from the data, and indicates expressions in common use that are
      suggested, but not actually supported, by the data. The paradoxes that exist in
      the common approaches for the case of a porous medium with a spatiallyvariable
      porosity are illustrated. A modified form of Darcy's law, and also of the Hubbert
      potential, is derived based upon fundamental notions of averaging. The modified
      form of Darcy's law derived here reduces to the conventional form for a
      homogeneous porous medium.

PMID- 15573588
TI  - Stimulated microbial reductive dechlorination following surfactant treatment at
      the Bachman Road site.
AB  - A pilot-scale demonstration of surfactant-enhanced aquifer remediation (SEAR) was
      conducted in July 2000 at the Bachman Road site located in Oscoda, MI. The
      Bachman aquifer is a shallow, relatively homogeneous, unconfined aquifer
      formation composed primarily of sandy glacial outwash with relatively low organic
      carbon content (0.02 wt %). A 6 wt % aqueous solution of Tween 80 (a nonionic,
      food-grade surfactant) was flushed through a localized dense nonaqueous phase
      liquid (DNAPL) source zone to recover approximately 19 L of tetrachloroethene
      (PCE). Post-treatment monitoring revealed PCE concentrations were reduced by up
      to 2 orders of magnitude within the source zone, and there was no evidence of
      concentration rebound after more than 450 d. Concentrations of PCE dechlorination
      products (trichloroethene, cis-1,2-dichloroethene) 450 d after SEAR operations
      ceased were more than 2 orders of magnitude greater than pretreatment values,
      suggesting stimulation of native dechlorination activity. Post-treatment
      monitoring detected increased concentrations of volatile fatty acids generated
      from the fermentation of residual-level Tween 80 surfactant. These field data
      suggest that Tween 80 not only induced and maintained anaerobiosis but also
      provided reducing equivalents to reductively dechlorinating populations present
      in the oligotrophic Bachman aquifer. Experience from this site supports
      application of staged treatment strategies that couple SEAR and microbial
      reductive dechlorination to enhance mass removal and reduce contaminant mass flux
      emanating from treated source zones.

PMID- 15573589
TI  - Aquasols: on the role of secondary minima.
AB  - Experiments are presented that test the hypothesis of deposition into and
      reentrainment from secondary minima during flow through porous media. The release
      of deposited particles following a decrease in ionic strength is inconsistent
      with deposition in the primary minimum of either simple DLVO interaction energy
      curves (which suggest that deposition is irreversible) or Born-DLVO interaction
      energy curves (which create a finite primary minimum that deepens with decreasing
      ionic strength). The observed release of particles is, on the other hand,
      consistent with deposition in the secondary minimum because this energy minimum
      decreases and can disappear with decreasing ionic strength. The implications for
      colloid transport of a reversible deposition process in the secondary minimum are
      very different from those of a process involving irreversible deposition in the
      primary minimum. First, particles that are continually captured and released will
      travel much farther in the subsurface than might be expected if the classic
      irreversible filtration model is applied. Second, and perhaps more significantly,
      deposition in the secondary well can increase with increasing particle size.
      Although particle transport by convective diffusion increases as particle size
      decreases, particle "attachment" in secondary minima decreases with decreasing
      particle size. Thus, smaller particles (those with diameters in the order of a
      few tens of nanometers) would be more effective in the facilitated transport of
      highly sorbing contaminants such as hydrophobic organic molecules, metals, and
      radionuclides. Other contaminants are themselves particles, such as viruses (tens
      of nanometers in diameter) and bacteria (near 1 microm in diameter). Due to this
      difference in size, viruses could be transported over much larger distances than
      bacteria. Third, the transport of colloids and, hence, the transport of
      contaminants associated with them, depends on the Hamaker constant of the
      particle-water-aquifer media system. Colloids of lower Hamaker constant are
      likely to be transported farther than colloids of higher Hamaker constant. The
      extent of adsorption of specific contaminants and the Hamaker constant for the
      particle-aquifer system are both characteristics of the particles and contribute
      to the effectiveness of colloid-facilitated transport. Finally, the solution
      chemistry of the pore waters (through pH, ionic strength, types of solutes, and
      the valence of the ions) ultimately controls the deposition and release of
      colloidal particles in porous media. The pH determines the charge density and
      surface potential of the surfaces. When the surfaces are similarly charged, their
      interaction can be unfavorable, with an energy barrier and secondary minimum. The
      ionic strength and valence of the ions determines the shape of the interaction
      energy curve, including the presence and height of the energy barrier and the
      presence and depth of the secondary well. Since the subsequent release of a
      particle depends on the mode in which the particle is deposited (primary or
      secondary), these factors are particularly important in determining the extent of
      colloid transport in the subsurface.

PMID- 15573590
TI  - Uncertainty analysis in a mechanistic model of bacterial regrowth in distribution
      systems.
AB  - The first generation of mechanistic models of bacterial regrowth in distribution
      systems (DS) provides insight into cause-and-effect relationships. However, the
      state of knowledge about the processes included in these models is insufficient
      to warrant deterministic predictions. Even if the process descriptions are
      reasonable, the uncertainty in values of key system constants limits predictions
      of bacterial growth. A new mechanistic model was developed to incorporate the
      accepted knowledge of physical, chemical, and biological processes with the
      hydraulic features in order to capture the unsteady state behavior of the DS.
      Sensitivitytesting showed that the extent of bacterial regrowth was affected
      mainly by the rate constants for chlorine decay reactions in bulk water and on
      the pipe wall and by the maximum growth rate constant of attached bacteria. A
      simple hypothetical network was used to evaluate the effects of uncertainty in
      these three system constants by running 100 Monte Carlo simulations. Cumulative
      probability plots showed a wide range of predictions for concentrations of
      bacteria and chlorine in bulk water at various nodes in the DS. The magnitude of
      these concentrations and the range of values were greatly affected by water
      residence time to each node. Once the chlorine residual is depleted, bacterial
      growth is mainly influenced by the amount of substrate available. However, high
      values of the coefficients for the maximum growth rate of attached bacteria, the
      chlorine decay in bulk water, and the chlorine decay by wall reaction did not
      necessarily lead to the maximum bacterial growth at a given location.

PMID- 15573591
TI  - Transport of Cryptosporidium oocysts in porous media: role of straining and
      physicochemical filtration.
AB  - The transport and filtration behavior of Cryptosporidium parvum oocysts in
      columns packed with quartz sand was systematically examined under repulsive
      electrostatic conditions. An increase in solution ionic strength resulted in
      greater oocyst deposition rates despite theoretical predictions of a significant
      electrostatic energy barrier to deposition. Relatively high deposition rates
      obtained with both oocysts and polystyrene latex particles of comparable size at
      low ionic strength (1 mM) suggest that a physical mechanism may play a key role
      in oocyst removal. Supporting experiments conducted with latex particles of
      varying sizes, under very low ionic strength conditions where physicochemical
      filtration is negligible, clearly indicated that physical straining is an
      important capture mechanism. The results of this study indicate that irregularity
      of sand grain shape (verified by SEM imaging) contributes considerably to the
      straining potential of the porous medium. Hence, both straining and
      physicochemical filtration are expected to control the removal of C. parvum
      oocysts in settings typical of riverbank filtration, soil infiltration, and slow
      sand filtration. Because classic colloid filtration theory does not account for
      removal by straining, these observations have important implications with respect
      to predictions of oocyst transport.

PMID- 15573592
TI  - Sugars--dominant water-soluble organic compounds in soils and characterization as
      tracers in atmospheric particulate matter.
AB  - The presence of saccharides is being reported for aerosols taken in urban, rural,
      and marine locales. The commonly found primary saccharides are alpha- and beta
      glucose, alpha- and beta-fructose, sucrose, and mycose with lesser amounts of
      other monosaccharides. Saccharide polyols are also found in some airsheds and
      consist mainly of sorbitol, xylitol, mannitol, erythritol, and glycerol. In
      temperate climate areas these compounds increase from negligible concentrations
      in winter aerosols (usually dominated by levoglucosan and related
      anhydrosaccharides from biomass burning) to a maximum in late spring-summer,
      followed by a decrease to winter. The composition of the saccharide mixtures
      suggests soil and associated microbiota as the source. Saccharide analyses of
      soils confirmed these compositions. Therefore, we propose resuspension of soil
      (also unpaved road dust) from agricultural activities as a major component of
      aerosol particles and the saccharides are the source specific tracers. In
      addition, the saccharides as well as the anhydrosaccharide derivatives from
      biomass burning are completely water soluble and thus contribute significantly to
      the total water-soluble mass of aerosols.

PMID- 15573593
TI  - Characterization of redox processes in shallow groundwater of Owens Dry Lake,
      California.
AB  - Redox status of shallow groundwaters (1-3 m depths) at Owens Dry Lake was studied
      to help guide mitigation efforts for attenuating dust generation from the dry
      lakebed. Redox conditions were characterized by Eh, oxidative capacity (OXC), and
      terminal electron accepting processes (TEAPs) as well as examining the energetics
      of TEAPs. Groundwater chemistry related to redox status was determined by major
      solute concentrations, dissolved gases (O2, H2, CH4), aqueous redox species (NO3,
      Mn2+, Fe2+/ Fe3+, SO4(2-)/HS-, DOC), and major redox sensitive components in the
      solid phase (extractable Fe/Mn). All of these measures of redox status indicate
      that sulfate reduction is the major process regulating redox conditions in most
      shallow groundwaters of Owens Dry Lake. Dissolved sulfate concentrations were
      regulated primarily by evaporation resulting in increasing concentrations as
      water migrates from the shoreline (<1 mM) to the center (up to 417 mM) of the dry
      lakebed. Eh values were generally in the range of -240 to -170 mV. The oxidative
      capacity demonstrates the dominant contribution of sulfate to OXC. The dominance
      of sulfate restricts further redox development, such as methanogenesis. Dissolved
      H2 concentrations ranged from 0.5 to 7.8 nM. According to the empirically defined
      H2 ranges, sulfate reduction was the most predominant TEAP. Moreover,
      thermodynamic calculations of TEAPs for H2 utilization support favorable
      energetics for both sulfate reduction and methanogenesis. The calculated
      available energy yield for sulfate reduction in the shallow groundwater of Owens
      Dry Lake was higher than other systems due to the high sulfate concentration.

PMID- 15573594
TI  - Preliminary study of lake dissolved organic matter in light of nanoscale
      supramolecular assembly.
AB  - Large-scale preparative high-performance size-exclusion chromatography (HPSEC)
      was performed to separate different molecular size fractions in milligram
      quantities from strongly colored dissolved organic matter (DOM) of a freshwater
      using a very mild conjugate acid-base pair (10 mM acetic acid-sodium acetate
      solution at pH 7.0 with an ionic strength of 6 x 10(-5)) as the mobile phase. The
      homogeneity-uniformity of different molecular size fractions in relation to their
      combined original mixture was verified by an analytical HPSEC system. In addition
      to molecular size distribution and basic spectroscopic characteristics, Fourier
      transform infrared spectroscopy was applied to specify structural features for
      different size fractions. The results demonstrate clearly that only a very small
      amount of conjugate organic acid-base pair is required to generate a powerful
      resolution for a DOM mixture, and very strong treatments with organic acids are
      not necessarily needed to reach a better SEC resolution. Most essential is the
      combined outcome of different HPSEC experiments and determined structural
      functionalities which indicate that almost all original DOM solutes are
      aggregated mixtures consisting of different associations possessing various
      molecular size ranges, which can be separated from their integrated whole as
      nearly homogeneous and uniform species. In summary, the present study strongly
      speaks for the need to direct the research of natural dissolved and colloidal
      organic carbon more strongly toward a nanoscale study of supramolecular
      assemblies. More precise knowledge about the primary, secondary, and tertiary
      structure of dissolved DOM constituents has its essential function, e.g., for
      environmental protection and utilization of surface waters.

PMID- 15573595
TI  - Simultaneous determination of carbonyls and NO2 in exhausts of heavy-duty diesel
      trucks and transit buses by HPLC following 2,4-dinitrophenylhydrazine cartridge
      collection.
AB  - A method combining 2,4-dinitrophenylhydrazine (DNPH) cartridge sampling and high
      performance liquid chromatography (HPLC) analysis has been used for the
      measurement of carbonyl and NO2 emissions from heavy-duty diesel trucks and
      transit buses. The reaction of NO2 with DNPH allows for the simultaneous and
      unambiguous determination of NO2 and carbonyl concentrations in exhaust samples.
      The potential coelution of the NO2-DNPH derivative with the formaldehyde-DNPH
      derivative under certain chromatographic conditions was investigated. Successful
      separation of these two species was achieved allowing for simultaneous
      determination of carbonyls and NO2 in the exhaust samples collected from heavy
      duty diesel (HDD) trucks and diesel, diesel/electric hybrid, diesel equipped with
      the continuously regenerating technology (CRT) particle traps, and compressed
      natural gas (CNG) transit buses tested over various drive cycles. Elevated NO2
      emissions from CRT-equipped buses were observed. The NO2/NOx volume ratios for
      HDD trucks and transit buses are discussed. A comparison of the DNPH
      derivatization with HPLC/UV-visible detection method with a chemiluminescence
      analyzer method for NO2 measurement is presented for a limited number of
      diesel/CRT and CNG buses.

PMID- 15573596
TI  - Chemical and mineralogical characterization of blast-furnace sludge from an
      abandoned landfill.
AB  - Blast-furnace sludge is generated during the production of pig iron and is
      disposed of in the environment in large surface landfills. We investigated blast
      furnace sludge samples of an abandoned landfill in order to determine its
      chemical and mineralogical nature and to evaluate some environmental hazards that
      may arise from this industrial waste. The mineralogical inventory, which was
      quantified by Rietveld refinement of XRD analyses using the fundamental-parameter
      approach, revealed that blast-furnace sludge is dominated by X-ray amorphous
      substances (with a mean of 590 g kg(-1)) including coke and (hydr)oxides of Fe,
      Si, Al, Zn, and Pb. Calcite (CaCO3) (136 g kg(-1)), dolomite (Ca,Mg[CO3]2) (14 g
      kg(-1)), quartz (SiO2) (55 g kg(-1)), kaolinite (Al2[OH]4Si2O5) (40 g kg(-1)),
      graphite (C) (27 g kg(-1)), and chemically not specified layered double
      hydroxides (28 g kg(-1)) were identified in almost all samples. Iron is present
      as magnetite (Fe3O4) (34 g kg(-1)), hematite (Fe2O3) (38 g kg(-1)), wuestite
      (FeO) (20 g kg(-1)) and alpha-iron (Fe0) (6 g kg(-1)). Chemically, blast-furnace
      sludge is dominated by C (190 g kg(-1)) and Fe (158 g kg(-1)) reflecting the
      process of pig-iron production. On the basis of total contents, environmentally
      problematic metals (including As) are Zn (32.6 g kg(-1)), Pb (10.3 g kg(-1)), Cd
      (81 mg kg(-1)), and As (129 mg kg(-1)). As the forested landfill is used by
      residents for leisure activities, the exposure assessment by pathway oral uptake
      of blast-furnace sludge particles by humans has to be critically evaluated,
      particularly as significant proportions of metals are acid-soluble. However,
      under the prevailing slightly alkaline pH values of the sludge (pH 7.6-9.2), the
      solubility of the metals is very low as indicated by low pore water
      concentrations. Currently, groundwater monitoring should be focused mainly on F-
      since the F- concentrations in the pore water of blast-furnace sludge are at high
      level (2.65-24.1 mg of F- L(-1)).

PMID- 15573597
TI  - Physicochemical characteristics and biological activities of seasonal atmospheric
      particulate matter sampling in two locations of Paris.
AB  - Fine particulate matter present in urban areas seems to be incriminated in
      respiratory disorders. The aim of this study was to relate physicochemical
      characteristics of PM2.5 (particulate matter collected with a 50% efficiency for
      particles with an aerodynamic diameter of 2.5 microm) to their biological
      activities toward a bronchial epithelial cell line 16-HBE. Two seasonal sampling
      campaigns of particles were realized, respectively, in a kerbside and an urban
      background station in Paris. Sampled-PM2.5 mainly consist of particles with a
      size below 1 microm and are mainly composed of soot as assessed by analytical
      scanning electron microscopy. The different PM2.5 samples contrasted in their PAH
      content, which was the highest in the kerbside station in winter, as well as in
      their metal content. Kerbside station samples were characterized by the highest
      Fe and Cu content, which appears correlated to their hydroxyl radical generating
      properties measured by electron paramagnetic resonance. Particles were compared
      by their capacity to induce cytotoxicity, intracellular ROS production, and
      proinflammatory cytokine release (GM-CSF and TNF-alpha). At a concentration of 10
      microg/cm2, all samples induced peroxide production and cytokine release to the
      similar extent in the absence of cytotoxicity. In conclusion, whereas the PM2.5
      samples differ by their PAH and metal composition, they induce the same
      biological responses likely either due to components bioavailability and/ or
      interactions between PM components.

PMID- 15573598
TI  - European-scale modeling of concentrations and distribution of polybrominated
      diphenyl ethers in the pentabromodiphenyl ether product.
AB  - The results from a modeling exercise utilizing the European variant (EVn) BETR
      multimedia environmental fate model are presented for selected polybrominated
      diphenyl ethers (PBDEs) of the technical penta- (Pe-) bromodiphenyl ether (BDE)
      product. The objectives of this study were to test PeBDE emission estimates from
      the literature for Europe by investigating the consistency between model
      predictions and ambient measurements to address the ability of the model to
      predict spatial variability and differences between congeners. Concurrently
      sampled and analyzed passive sampling air data, together with soil and grass
      data, were used as key model validation tools. The model steady-state simulations
      gave generally good agreement with measured data for BDE-47 and -99 with greater
      discrepancies for heavier congeners (e.g., BDE-153). To predict future
      atmospheric concentration trends, the model was used in its fully dynamic mode
      over the period 1970--2010. It was predicted that atmospheric concentrations
      peaked around 1997, declining with an overall "disappearance" half-life of 4.8
      years. Soil and grass levels were underestimated by the model; possible reasons
      for differences with measurement data are further explored. Finally, the
      importance of temporally and spatially resolved environmental data sets is
      highlighted, while improved quantification of degradation half-lives is essential
      to better understand and predict the behavior of BDE congeners in PeBDE.

PMID- 15573599
TI  - Use of fecal steroids to infer the sources of fecal indicator bacteria in the
      Lower Santa Ana River Watershed, California: sewage is unlikely a significant
      source.
AB  - The Santa Ana River (SAR), CA and adjacent wetlands have been identified as
      potential sources of fecal indicator bacteria (FIB) to the surf zone at
      Huntington Beach, CA. A suite of fecal steroids, including coprostanol (COP),
      epicoprostanol (eCOP), cholesterol (CHOE), cholestanol (CHOA), alpha-cholestanone
      (aONE), beta-cholestanone (bONE), beta-sitosterol (bSIT), stigmasterol (STIG),
      stigmastanol (STAN), and campesterol (CAM), were used as chemical markers to
      examine whether sewage was a significant source of FIB within the lower Santa Ana
      River watershed. A total of 54 water samples were collected from three locations
      in the intertidal zone near the mouth of the Santa Ana River at different tidal
      stages. Steroid ratios in SAR samples were different from those found in raw and
      treated sewage from a local wastewater treatment plant or in nearby effluent
      plume and did not appear to be influenced by the sampling location, daily tides,
      and spring/neap tidal cycle. The characteristics of steroid ratios suggested a
      diagenetic ratherthan a biogenic source forthe COP content of the samples. The
      log-based concentrations of COP and FIB in the SAR samples were not significantly
      correlated, inconsistent with sewage being the source of FIB in the study area.
      In addition, multivariate statistical analysis showed that the concentrations of
      FIB were better correlated with bird fecal steroids than with the typical sewage
      sterols. The results implied that sewage was not a significant source of fecal
      steroids, and therefore perhaps FIB to the study area. Instead, birds may be one
      possible source of the intermittently high levels of FIB observed in the lower
      Santa Ana River watershed and the nearby surf zone.

PMID- 15573600
TI  - Climate-induced episodic acidification of streams in central ontario.
AB  - In this study we have analyzed the hydrochemical effect of drought conditions
      during 311 hydrological episodes in nine headwater streams in central Ontario
      over the past 20 years. Acid Neutralization Capacity (ANC) was logarithmically
      correlated (p<0.05) to antecedent discharge in eight of the nine streams, with
      the largest decline in ANC occurring after low antecedent flow. In eight of the
      nine streams SO4(2-) was the most important driving mechanism of ANC decline, but
      dilution as well as organic acidity was important in several streams. No decrease
      in the SO4(2-) driven ANC decline was observed over the 20 year study period
      despite a approximately 40% reduction in SO4(2-) deposition. The strong
      correlation between ANC decline and low antecedent discharge demonstrates that
      episodic acidification during rain events is strongly associated with preceding
      drought conditions, especially in wetland-dominated catchments. The results have
      important implications for recoveryfrom acidification, especially in northern
      ecosystems where climate scenarios forecast that warmer and drier conditions will
      be more common.

PMID- 15573601
TI  - Pu(V)O2+ adsorption and reduction by synthetic magnetite (Fe3O4).
AB  - Changes in aqueous- and solid-phase Pu oxidation state were monitored over time
      in magnetite (Fe3O4) suspensions containing 239Pu(V)-amended 0.01 M NaCl.
      Oxidation state distribution was determined by leaching of Pu into an aqueous
      phase followed by an ultrafiltration/solvent extraction technique. The capability
      of the technique to measure Pu oxidation state distribution was verified using
      230Th(IV), 237Np(V), and 233U(VI) as oxidation state analogues. Reduction of
      Pu(V) was observed at all pH values (pH 3 to 8) and magnetite concentrations (10
      to 100 m2 L(-1)). In the pH range 5 to 8, adsorption was a rate-limiting step,
      and reduction was mediated by the solid phase; at pH 3 reduction occurred in the
      aqueous phase. The overall reaction (describing both adsorption and reduction of
      Pu(V)) was found to be approximately first order with respect to the magnetite
      concentration and of order -0.34+/-0.02 with respect to the hydrogen ion
      concentration. Assuming first order dependence with respect to Pu, the overall
      reaction rate constant was calculated as k(rxn) = 4.79+/-0.62 x 10(-8) (m(-2)
      L)0.99(mol(-1) L)-0.34(s(-1)). The Pu(IV) solid-phase species became more stable
      over time.

PMID- 15573602
TI  - Oxidation of the cyanobacterial hepatotoxin microcystin-LR by chlorine dioxide:
      reaction kinetics, characterization, and toxicity of reaction products.
AB  - Cyanobacteria are known producers of cytotoxins, hepatotoxins, and neurotoxins.
      The main toxins are microcystins, cyclic heptapeptide hepatotoxins, produced by
      strains of several cyanobacterial genera frequently found in eutrophied
      freshwaters. Due to the acute and chronic toxicity of microcystins, successful
      removal of these toxins in drinking water treatment processes is of increasing
      concern. In the present work the kinetics of microcystin-LR (MC-LR) oxidation by
      chlorine dioxide (ClO2) was studied with UV-spectrometry and high performance
      liquid chromatography (HPLC). Characterization of reaction products was performed
      with mass spectrometric (MS) analysis, while the toxicity of reaction products
      was tested with a protein phosphatase inhibition assay (PPIA). The main reaction
      products formed, dihydroxy isomers of MC-LR as identified by MS, were nontoxic
      according to the PPIA. The overall rate constant k for the reaction between MC-LR
      and ClO2 at 293 K and pH 5.65 was modest, k = 1.24 M(-1) s(-1), suggesting that
      ClO2 is not a suitable oxidant for the degradation of microcystins in drinking
      water treatment processes.

PMID- 15573603
TI  - Spectroscopic characterization of the uranium carbonate andersonite
      Na2Ca[UO2(CO3)3] x 6H2O.
AB  - The uranium carbonate andersonite Na2Ca[UO2(CO3)3] x 6H2O was synthesized and
      identified with classical analytical and spectroscopic methods. The classical
      methods applied were powder X-ray diffraction (XRD), nitric acid digestion, and
      scanning electron microcopy combined with energy-dispersive spectroscopy
      (SEM/EDS). To characterize andersonite spectroscopically, time-resolved laser
      induced fluorescence spectroscopy (TRLFS), X-ray photoelectron spectroscopy
      (XPS), and Fourier transform infrared spectroscopy (FT-IR) were used. Natural and
      synthetic andersonite samples were characterized with the nondestructive TRLFS by
      six fluorescence emission bands at 470.6, 486.1, 505.4, 526.7, 549.6, and 573.9
      nm. In addition, andersonite was characterized by FT-IR measurements by the
      appearance of the asymmetric stretching vibration of the uranyl cation
      [v3(UO2(2+))] at 902 cm(-1) with a shoulder at 913 cm(-1). XPS measurements
      verified the composition of the synthetic andersonite sample. The measured
      intensity ratios of the XPS lines agree with the stoichiometry of
      Na2Ca[UO2(CO3)3] x 6H2O. The XPS features of the inner valence molecular orbitals
      are characteristic of the [UO2(CO3)3]4- structural moiety. These spectroscopic
      methods can be used to identify in a fingerprinting procedure secondary U(VI)
      phases in mixtures with other phases or as thin coatings on mineral and rock
      surfaces.

PMID- 15573604
TI  - Stability of cyanogen chloride in the presence of free chlorine and
      monochloramine.
AB  - Cyanogen chloride (CNCl) is a disinfection byproduct found in chlorinated and
      chloraminated drinking water. Although there is an apparent greater association
      of CNCI with chloraminated water relative to chlorination systems, it was not
      clear whether these phenomenological observations are explained by differences in
      the stability or formation potentials of CNCI between the two disinfectants. In
      this study, the stability of CNCl was examined in the presence of free chlorine
      and monochloramine using membrane introduction mass spectrometry. CNCI decomposes
      relatively rapidly when free chlorine is present but is stable in the presence of
      monochloramine. The decomposition kinetics and observed reaction products are
      consistent with a hypochlorite-catalyzed hydrolysis mechanism, and the rate law
      is described by (d[CNCl]/dt) = - kOCl[CNCl][OCl-]. At 25 degrees C, pH 7, and a
      free chlorine residual of 0.5 mg/L as Cl2, the half-life of CNCl is approximately
      60 min, suggesting significant decomposition is expected over disinfection time
      scales. Under some winter season temperature conditions, however, the decay half
      life of CNCl can be longer than typical disinfection contact times. The results
      of this study demonstrate that the observed association of CNCl with
      chloramination systems can in part be explained by the differences in its
      stability with chlorine and chloramines.

PMID- 15573605
TI  - Application of controlled mesocosms for understanding mercury air-soil-plant
      exchange.
AB  - Whole system elemental mercury (Hg0) flux was measured for approximately 1.5
      years using two large gas exchange mesocosms containing approximately 100 two
      year old aspen trees (Populus tremuloides) planted in soil with elevated mercury
      concentrations (12.3 microg/g). We hypothesized that during leafout, whole
      mesocosm Hg0 flux would increase due to movement of Hg0 in the transpiration
      stream from the soil to the air. This hypothesis was not supported; plants were
      found to assimilate Hg0 from the contaminated air, and whole system Hg0 emissions
      were reduced as plants leafed-out due to shading of the soil. Surface
      disturbance, watering, and increases in soil moisture, light, and temperature
      were all found to increase whole system Hg0 flux, with light being a more
      significant factor. Although surface soils were maintained at 15-20% moisture,
      daily watering caused pulses of Hg0 to be released from the soil throughout the
      experiment. Data developed in this experiment suggested that those processes
      acting on the soil surface are the primary influence on Hg emissions and that the
      presence of vegetation, which shields soil surfaces from incident light, reduces
      Hg emissions from enriched soils.

PMID- 15573606
TI  - Cd and Zn uptake kinetics in Daphnia magna in relation to Cd exposure history.
AB  - The uptake kinetics of Cd and Zn in a freshwater cladoceran Daphnia magna after
      exposure to different concentrations of Cd for various durations was quantified.
      The accumulated Cd concentrations increased with ambient Cd concentration and
      exposure duration. As a detoxification mechanism, metallothioneins (MTs) were
      induced when the Cd preexposure condition was beyond the noneffect threshold. The
      MT induction was dependent on both Cd concentration and duration of preexposure.
      Increasing the Cd exposure concentration to 20 microg L(-1) for 3 d caused a 44%
      reduction in Cd assimilation efficiency (AE, the fraction assimilated by the
      animals after digestion) by the daphnids from the dietary phase, but a 2.4-fold
      increase in Zn AE. Generally, the dissolved metal uptake rate was not
      significantly affected by the different Cd preexposure regimes, except at a much
      higher Cd concentration (20 microg L(-1)) when the Zn influx was enhanced.
      Significant effects from Cd exposure on the ingestion rate of the daphnids were
      also observed. When the MT synthesis was not coupled with the accumulated Cd
      tissue burden (e.g., a delay in MT synthesis), apparent Cd toxicity on the
      feeding behavior and the Cd AE was observed, thus highlighting the importance of
      MTs in modifying the metal uptake kinetics of D. magna. Overall, daphnids
      responded to acute Cd exposure by reducing their Cd AE and ingestion, whereas
      they developed a tolerance to Cd following chronic exposure. The bioavailability
      of Zn was enhanced as a result of Cd preexposure. This study highlights the
      important influences of Cd preexposure history on the biokinetics and potential
      toxicity of Cd and Zn to D. magna.

PMID- 15573607
TI  - Effects of phosphate on uranium(VI) adsorption to goethite-coated sand.
AB  - U(VI)-phosphate interactions are important in governing the subsurface mobility
      of U(VI) in both natural and contaminated environments. We studied U(VI)
      adsorption on goethite-coated sand (to mimic natural Fe-coated subsurface
      materials) as a function of pH in systems closed to the atmosphere, in both the
      presence and the absence of phosphate. Our results indicate that phosphate
      strongly affects U(VI) adsorption. The effect of phosphate on U(VI) adsorption
      was dependent on solution pH. At low pH, the adsorption of U(VI) increased in the
      presence of phosphate, and higher phosphate concentration caused a larger extent
      of increase in U(VI) adsorption. Phosphate was strongly bound by the goethite
      surface in the low pH range, and the increased adsorption of U(VI) at low pH was
      attributed to the formation of ternary surface complexes involving both U(VI) and
      phosphate. In the high pH range, the adsorption of U(VI) decreased in the
      presence of phosphate at low total Fe concentration, and higher phosphate
      concentration caused a larger extent of decrease in U(VI) adsorption. This
      decrease in U(VI) adsorption was attributed to the formation of soluble uranium
      phosphate complexes. A surface complexation model (SCM) was proposed to describe
      the effect of phosphate on U(VI) adsorption to goethite. This proposed model was
      based on previous models that predict U(VI) adsorption to iron oxides in the
      absence of phosphate and previous models developed to predict phosphate
      adsorption on goethite. A postulated ternary surface complex of the form of
      (>FePO4UO2) was included in our model to account for the interactions between
      U(VI) and phosphate. The model we established can successfully predict U(VI)
      adsorption in the presence of phosphate under a range of conditions (i.e., pH,
      total phosphate concentration, and total Fe concentration).

PMID- 15573608
TI  - Colloid formation at waste plume fronts.
AB  - Highly saline and caustic tank waste solutions containing radionuclides and toxic
      metals have leaked into sediments at U.S. Department of Energy (DOE) facilities
      such as the Hanford Site (Washington state). Colloid transport is frequently
      invoked to explain migration of radionuclides and metals in the subsurface. To
      understand colloid formation during interactions between highly reactive fluids
      and sediments and its impact on contaminant transport, we simulated tank waste
      solution (TWS) leakage processes in laboratory columns at ambient and elevated
      (70 degrees C) temperatures. We found that maximum formation of mobile colloids
      occurred at the plume fronts (hundreds to thousands times higher than within the
      plume bodies or during later leaching). Concentrations of suspended solids were
      as high as 3 mass %, and their particle sizes ranged from tens of nanometers to a
      few micrometers. Calcium carbonate is always one of the dominant phases of the
      plume front colloids, while the other phases varied with solution pH and
      temperature. During infiltration of the leaked high-Na+ waste solution, rapid and
      completed Na+ replacement of exchangeable Ca2+ and Mg2+ from the sediment caused
      accumulation of these divalent cations at the moving plume front. Precipitation
      of supersaturated Ca2+/Mg2+-bearing minerals caused dramatic pH reduction atthe
      plume front. In turn, the reduced pH caused precipitation of other minerals. This
      understanding can help predict the behavior of contaminant trace elements carried
      by the tank waste solutions and could not have been obtained through conventional
      batch studies.

PMID- 15573609
TI  - Arsenic sequestration by ferric iron plaque on cattail roots.
AB  - Typha latifolia (cattail) sequesters arsenic within predominantlyferric iron root
      coatings, thus decreasing mobility of this toxic element in wetland sediments.
      Element-specific XRF microtomographic imaging illustrated a high spatial
      correlation between iron and arsenic in root plaques, with little arsenic in the
      interior of the roots. XANES analyses demonstrated that the plaque was
      predominantly ferric iron and contained approximately 20% As(III) and 80% As(V),
      which is significant because the two oxidation states form species that differ in
      toxicity and mobility. For the first time, spatial distribution maps of As
      oxidation states were developed, indicating that As(III) and As(V) are both
      fairly heterogeneous throughoutthe plaque. Chemical extractions showed that As
      was strongly adsorbed in the plaque rather than coprecipitated. Iron and arsenic
      concentrations ranged from 0.03 to 0.8 g Fe g(-1) wet plaque and 30 to 1200
      microg As g(-1) wet plaque, consistent with a mechanism of As adsorption onto
      Fe(III) oxyhydroxide plaque. Because this mechanism decreases the concentrations
      of both As(III) and As(V) in groundwater, we propose that disruption of
      vegetation could increase the concentrations of mobile arsenic.

PMID- 15573610
TI  - NO and NO2 emission ratios measured from in-use commercial aircraft during taxi
      and takeoff.
AB  - In August 2001, the Aerodyne Mobile Laboratory simultaneously measured NO, NO2,
      and CO2 within 350 m of a taxiway and 550 m of a runway at John F. Kennedy
      Airport. The meteorological conditions were such that taxi and takeoff plumes
      from individual aircraft were clearly resolved against background levels. NO and
      NO2 concentrations were measured with 1 s time resolution using a dual tunable
      infrared laser differential absorption spectroscopy instrument, utilizing an
      astigmatic multipass Herriott cell. The CO2 measurements were also obtained at 1
      s time resolution using a commercial non-dispersive infrared absorption
      instrument. Plumes were measured from over 30 individual planes, ranging from
      turbo props to jumbo jets. NOx emission indices were determined by examining the
      correlation between NOx (NO + NO2) and CO2 during the plume measurements. Several
      aircraft tail numbers were unambiguously identified, allowing those specific
      airframe/engine combinations to be determined. The resulting NOx emission indices
      from positively identified in-service operating airplanes are compared with the
      published International Civil Aviation Organization engine certification test
      database collected on new engines in certification test cells.

PMID- 15573611
TI  - Chronic effects of dietary selenium on juvenile Sacramento splittail
      (Pogonichthys macrolepidotus).
AB  - The chronic effects of dietary selenium (Se) exposure in juvenile Sacramento
      splittail (Pogonichthys macrolepidotus) were investigated in the laboratory. A
      total of 960 (40 fish per tank, 3 tanks per diet) 7-month-old juvenile splittail
      were fed one of eight Purified-Casein diets supplemented with selenized yeast for
      9 months in a flow-through system. These diets contained the following: 0.4
      (control), 0.7, 1.4, 2.7, 6.6, 12.6, 26.0, and 57.6 mg of Se kg(-1) dry weight.
      Survival, Se tissue concentration, growth, gross morphology, and liver
      histopathology were assessed at 5- and 9-month of exposure. Mortalities occurred
      only in the two highest Se treatments and were accounted for 8.3 and 18.3% at 5
      month and 10.0 and 34.3% at 9-month, respectively. Liver and muscle Se
      concentration were significantly correlated with dietary Se concentration. Fish
      exposed to 0.4-12.6 mg of Se kg(-1) diets had reached equilibrium in liver Se
      concentration by 5 month. Splittail fed diets at concentrations > or =26.0 mg of
      Se kg(-1) had not reached equilibrium in liver, and muscle Se concentrations and
      grew significantly slower (p < 0.05) at 5- and 9-month exposure. Se-induced
      deformities were observed in fish fed > or =2.7 mg of Se kg(-1) diets at 5-month
      and in fish fed > or =0.7 mg of Se kg(-1) diets at 9-month. Fish fed 26.0 and
      57.6 mg of Se kg(-1) diets had higher liver lesion scores at 5-month while fish
      fed 6.6 and 57.6 mg of Se kg(-1) diet had higher liver lesion scores at 9-month.
      Results indicate that survivals, growth, changes of tissue Se concentrations, and
      histopathology of juvenile splittail were dose-dependent, but their response
      thresholds to dietary Se concentrations differed and depended on treatment
      concentrations and duration of exposure. Chronic exposure to 6.6 mg of Se kg(-1)
      diet induced deleterious health effects that can potentially impact survival of
      juvenile splittail.

PMID- 15573612
TI  - Quantification of variability and uncertainty for air toxic emission inventories
      with censored emission factor data.
AB  - Probabilistic emission inventories were developed for urban air toxic emissions
      of benzene, formaldehyde, chromium, and arsenic for the example of Houston.
      Variability and uncertainty in emission factors were quantified for 71-97% of
      total emissions, depending upon the pollutant and data availability. Parametric
      distributions for interunit variability were fit using maximum likelihood
      estimation (MLE), and uncertainty in mean emission factors was estimated using
      parametric bootstrap simulation. For data sets containing one or more nondetected
      values, empirical bootstrap simulation was used to randomly sample detection
      limits for nondetected values and observations for sample values, and parametric
      distributions for variability were fit using MLE estimators for censored data.
      The goodness-of-fit for censored data was evaluated by comparison of cumulative
      distributions of bootstrap confidence intervals and empirical data. The emission
      inventory 95% uncertainty ranges are as small as -25% to +42% for chromium to as
      large as -75% to +224% for arsenic with correlated surrogates. Uncertainty was
      dominated by only a few source categories. Recommendations are made for future
      improvements to the analysis.

PMID- 15573613
TI  - Phosphorus compounds in sequential extracts of animal manures: chemical
      speciation and a novel fractionation procedure.
AB  - Pollution of water bodies by phosphorus in runoff from soil amended with animal
      manures is one of the greatest threats to water quality in developed countries.
      The environmental fate of manure phosphorus is determined in part by its chemical
      composition, yet extraction procedures to assess this are poorly developed and
      provide no structural information. We used solution 31P NMR spectroscopy to
      quantify phosphorus compounds in sequential extracts of three contrasting manures
      (broiler litter, beef-cattle manure, swine manure). Using a procedure originally
      developed for soils, but commonly applied to manures, phosphorus was extracted
      sequentially with deionized water, 0.5 M NaHCO3, 0.1 M NaOH, and 0.5 M HCl. Water
      and NaHCO3 extracted readily soluble compounds, including phosphate,
      phospholipids, DNA, and simple phosphate monoesters, which are mobile in soil and
      biologically available. In contrast, NaOH and HCl extracted poorly soluble
      compounds, including phytic acid (myoinositol hexakisphosphate). The latter is
      immobile in soil and of limited biological availability. Based on these results,
      we developed a simplified two-step fractionation procedure involving extraction
      of readily soluble phosphorus in 0.5 M NaHCO3 followed by extraction of stable
      phosphorus in a solution containing 0.5 M NaOH and 50 mM EDTA. This revised
      procedure separates manure phosphorus into structurally defined fractions with
      environmental relevance and will facilitate research on this important aspect of
      environmental science.

PMID- 15573614
TI  - Comparison of seven protocols to identify fecal contamination sources using
      Escherichia coli.
AB  - Microbial source tracking (MST) uses various approaches to classify fecal
      indicator microorganisms to source hosts. Reproducibility, accuracy, and
      robustness of seven phenotypic and genotypic MST protocols were evaluated by use
      of Escherichia coli from an eight-host library of known-source isolates and a
      separate, blinded challenge library. In reproducibility tests, measuring each
      protocol's ability to reclassify blinded replicates, only one (pulsed-field gel
      electrophoresis; PFGE) correctly classified all test replicates to host species;
      three protocols classified 48-62% correctly, and the remaining three classified
      fewer than 25% correctly. In accuracy tests, measuring each protocol's ability to
      correctly classify new isolates, ribotyping with EcoRI and PvuII approached 100%
      correctclassification but only 6% of isolates were classified; four of the other
      six protocols (antibiotic resistance analysis, PFGE, and two repetitive-element
      PCR protocols) achieved better than random accuracy rates when 30-100% of
      challenge isolates were classified. In robustness tests, measuring each
      protocol's ability to recognize isolates from nonlibrary

PMID- 15573615
TI  - Decomposition of environmentally persistent perfluorooctanoic acid in water by
      photochemical approaches.
AB  - The decomposition of persistent and bioaccumulative perfluorooctanoic acid (PFOA)
      in water by UV-visible light irradiation, by H202 with UV-visible light
      irradiation, and by a tungstic heteropolyacid photocatalyst was examined to
      develop a technique to counteract stationary sources of PFOA. Direct photolysis
      proceeded slowly to produce CO2, F-, and short-chain perfluorocarboxylic acids.
      Compared to the direct photolysis, H2O2 was less effective in PFOA decomposition.
      On the other hand, the heteropolyacid photocatalyst led to efficient PFOA
      decomposition and the production of F- ions and CO2. The photocatalyst also
      suppressed the accumulation of short-chain perfluorocarboxylic acids in the
      reaction solution. PFOA in the concentrations of 0.34-3.35 mM, typical of those
      in wastewaters after an emulsifying process in fluoropolymer manufacture, was
      completely decomposed by the catalyst within 24 h of irradiation from a 200-W
      xenon-mercury lamp, with no accompanying catalyst degradation, permitting the
      catalyst to be reused in consecutive runs. Gas chromatography/mass spectrometry
      (GC/MS) measurements showed no trace of environmentally undesirable species such
      as CF4, which has a very high global-warming potential. When the (initial
      PFOA)/(initial catalyst) molar ratio was 10: 1, the turnover number for PFOA
      decomposition reached 4.33 over 24 h of irradiation.

PMID- 15573616
TI  - Degradation of methylparathion in aqueous solution by electrochemical oxidation.
AB  - The electrochemical degradation of methylparathion has been investigated by using
      Ti/Pt as anode, Stainless Steel 304 as cathode, and sodium chloride as
      electrolyte. The pesticide is rapidly degraded, but full mineralization is not
      observed. Degradation products have been monitored through gas chromatography and
      mass spectrometry, and the overall degradation process has been monitored through
      dissolved and particulate organic carbon, sulfur, and phosphorus measurements.
      Several intermediates have been identified, and oxalic, formic, and acetic acids
      as well as tetraphosphorus trisulfide have been recognized as final products of
      the degradation process. A proposed mechanism of the process is presented.

PMID- 15573617
TI  - Particles in filter effluent: the roles of deposition and detachment.
AB  - Particles in the effluent of granular media filters can be classified as influent
      particles that were never removed or as particles that detached after prior
      deposition. To determine the effects of particle size, filter media depth and
      filter run duration on the relative fraction of each class, laboratory
      experiments were performed using suspensions of four sizes of polystyrene
      particles (0.2, 1.2, 2.5, and 4.0 microm diameters) that were destabilized with
      0.04 M calcium chloride and continuously supplied to filters after flocculation.
      To investigate particle attachment alone, three sizes (1.4, 4.0, and 9 microm) of
      fluorescent microspheres (FM) were periodically pulse injected immediately ahead
      of the filter media. Detachmentwas assessed as the difference between net removal
      (particle counts) and deposition (FM counts). FM deposition followed theory,
      while results show that particle detachment was significant from an early phase
      of filtration (100 minutes). The detached fraction of effluent particles
      increased with particle size (1 to 12 microm range) and filter depth. These model
      system results suggest that detachment plays a significant role in the origin of
      filter effluent particles in full-scale water treatment systems.

PMID- 15573618
TI  - Immobilized N-methyl-D-glucamine as an arsenate-selective resin.
AB  - Immobilization of N-methyl-D-glucamine (NMDG) on poly(vinylbenzyl chloride) beads
      yields an effective and highly selective sorbent for arsenate ions. Three
      important parameters in the resin's high As(V) affinity and selectivity are the
      structure of the ligand, its ionic form, and the crosslink density of the
      polymer. The NMDG resin crosslinked with 2 wt % divinylbenzene is far more
      selective than commercially available analogues, especially when sulfate and
      chloride ions are present in solution at high concentrations. Selectivity studies
      at neutral pH indicate that the protonated tertiary amine moiety is an important
      component of the complexation mechanism. The NMDG resin also has a high affinity
      for the un-ionized As(V) species at pH 1.

PMID- 15573619
TI  - Uptake of weathered DDT in vascular plants: potential for phytoremediation.
AB  - Since the discovery of its insecticidal properties and its subsequent widespread
      use, DDT [2,2-bis(chlorophenyl)-1,1,1-trichloroethane] has accumulated in the
      environment, having a wide range of adverse effects on nontarget species. Due to
      their hydrophobicity, DDT and other persistent organic pollutants are difficult
      to remove from contaminated soils, and increasingly so through time as weathering
      occurs. Phytoremediation is an emerging plant-based technology that may be used
      to cost-effectively remove or neutralize contaminants in the environment. For
      some phytoremediation strategies, it must first be possible to translocate
      hydrophobic chemicals across the root and through the shoot via an aqueous
      transpiration stream. The objective of this study was to compare the ability of
      five plant varieties (zucchini, tall fescue, alfalfa, rye grass, and pumpkin) to
      mobilize and translocate DDT. Plants were grown in the greenhouse in soil
      contaminated with DDT and its metabolites, DDD and DDE (sigmaDDT refers to all of
      DDT, DDD, and DDE) at two concentrations (high approximately 3700 ng/g, and low
      approximately 150 ng/g). All trays were covered with laboratory Parafilm to limit
      volatilization. Cucurbita pepo species (pumpkin and zucchini) achieved the
      highest translocation and bioaccumulation factors, and also extracted the highest
      absolute amounts of sigmaDDT from both the high and low sigmaDDT soils. In the
      high sigmaDDT soil treatment, pumpkin accumulated 1519 ng of sigmaDDT in the
      roots and 57,536 ng of sigmaDDT in the shoots, and zucchini accumulated 2043 ng
      of sigmaDDT in the roots and 35,277 ng of sigmaDDT in the shoots. With the
      exception of alfalfa and pumpkin, principal component analysis detected no
      preferential translocation or transformation of sigmaDDT compounds within the
      plant. The success of the Cucurbita pepo species in this study to extract and
      translocate such hydrophobic molecules may be related to their high transpiration
      volume, large above-ground biomass, and composition of root exudates. This
      suggests potential for their application in phytoremediation.

PMID- 15573620
TI  - Establishing and elucidating reduction as the removal mechanism of Cr(VI) by
      reclaimed limestone residual RLR (Modified Steel Slag).
AB  - The viability of utilizing Reclaimed Limestone Residual RLR (Modified Steel Slag)
      to remove hexavalent chromium Cr(VI) from the aqueous phase was investigated. A
      physical characterization of RLR showed that it is composed of various minerals
      some of which can reduce and others adsorb Cr(VI). Preliminary results showed
      that RLR significantly reduced the concentration of Cr(VI) from the aqueous
      phase. Adsorption competition tests with orthophosphate (HP04(2-)) and sulfate
      (SO4(2-)) showed that Cr(VI) was still effectively reduced from solution
      regardless of the competing anions present. Kinetic tests based on the
      relationship d[Cr(VI)]/dt = kCr[RLR]alpha[Cr(VI)]beta showed that under initially
      neutral to basic conditions kCr = 3.45+/-(0.25) x 10(-4) mg0.4 L(-0.4) h(-1),
      alpha = 0.9, and beta = -0.3, while under initially acidic conditions kCr =
      5.65+/-(1.055) x 10(-1) mg(-0.4) L0.4 h(-1), alpha = 2.2, and beta = -0.8.
      Stirred batch tests with RLR in deionized water showed significant drops in the
      redox potential (Eh), and in the presence of oxygen Eh values dropped to between
      50 and 100 mV while in the absence of oxygen Eh values as low as -200 mV were
      observed. These results lead to the conclusion that redox mechanisms were
      responsible for the reduction of hexavalent chromium by RLR.

PMID- 15573621
TI  - Energy intensity of computer manufacturing: hybrid assessment combining process
      and economic input-output methods.
AB  - The total energy and fossil fuels used in producing a desktop computer with 17
      in. CRT monitor are estimated at 6400 megajoules (MJ) and 260 kg, respectively.
      This indicates that computer manufacturing is energy intensive: the ratio of
      fossil fuel use to product weight is 11, an order of magnitude larger than the
      factor of 1-2 for many other manufactured goods. This high energy intensity of
      manufacturing, combined with rapid turnover in computers, results in an annual
      life cycle energy burden that is surprisingly high: about 2600 MJ per year, 1.3
      times that of a refrigerator. In contrast with many home appliances, life cycle
      energy use of a computer is dominated by production (81%) as opposed to operation
      (19%). Extension of usable lifespan (e.g. by reselling or upgrading) is thus a
      promising approach to mitigating energy impacts as well as other environmental
      burdens associated with manufacturing and disposal.

PMID- 15573622
TI  - Comment on "modeling maximum adsorption capacities of soot and soot-like
      materials for PAHs and PCBs".

PMID- 15573623
TI  - Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (I).
AB  - Gut-associated lymphoid tissue (GALT) is the largest lymphoid organ in the body.
      This is not surprising considering the huge load of antigens (Ags) from food and
      commensal bacteria with which it interacts on a daily basis. Gut-associated
      lymphoid tissue has to recognise and allow the transfer of beneficial Ags whilst
      concurrently dealing with and successfully removing putative and overtly harmful
      Ags. This distinctive biological feature of GALT is believed to be crucial to
      good health. Deregulation or dysfunction of GALT is thought to predispose to
      inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease.
      The exact mechanism(s) underlying the pathogenesis of IBD is (are) poorly
      understood and the immunological defects in GALT are poorly documented. Advances
      in immunology have highlighted the importance of dendritic cells (DCs), which are
      the key Ag presenting cells in tissues and lymphoid compartments. Their crucial
      role in GALT, in health and disease is discussed in this review. Interaction of
      DCs with T cells in the gut produces a subset of T lymphocytes, which have
      immunosuppressive function. Inappropriate Ag uptake and presentation to naive T
      cells in mesenteric lymph nodes may lead to T cell tolerance in GALT. These
      various complex factors in the gut are discussed and their possible relevance to
      IBD evaluated.

PMID- 15573624
TI  - A randomised controlled trial comparing two methods of teaching medical students
      trauma and orthopaedics: traditional lectures versus the "donut round".
AB  - OBJECTIVE: To assess whether a new form of teaching, the 'donut round', is as
      good at imparting factual knowledge as interactive lectures in both the short
      term and the long-term. DESIGN: Randomised controlled trial. SETTING: University
      of Oxford Medical School. PARTICIPANTS: 106 fifth year clinical medical students
      taught half of their A&E/trauma course by donut round and half by lecture. MAIN
      OUTCOME MEASURES: The results of multiple choice questions (MCQs) divided
      according to how the material was taught. Three MCQ papers were set: one at the
      end of a four-week course, one approximately 10 weeks later and a final exam
      approximately 17 months after the first. RESULTS: At the first MCQ, the average
      result for questions taught by donut round was 41.0 (out of 50) and for those
      taught by conventional lecture was 40.1. At 10 weeks these averages fell to 36.3
      and 37.3 and at 17 months they were 38.7 and 38.1, respectively. None of these
      pairs were significantly different. Ratios were calculated for each candidate by
      dividing their donut round score by their lecture score. The average ratios for
      the first, second and third MCQ papers were: 1.029, 1.007 and 1.027,
      respectively, and were not significantly different. The individual ratios of all
      candidates in all three MCQs were plotted against their equivalent total mark.
      The calculated linear regression showed a statistically significant advantage of
      donut rounds over lectures in those candidates who scored a total mark less than
      89 (n=260, p=0.02). CONCLUSIONS: Donut rounds are at least as good as lectures in
      imparting factual knowledge and may provide a selective advantage to weaker
      students.

PMID- 15573625
TI  - Non-operative management of blunt hepatic injury in multiply injured adult
      patients.
AB  - BACKGROUND: Non-operative management of blunt liver trauma has now evolved into a
      common practice especially since abdominal CT has enabled a more precise
      evaluation of these patients. CLINICAL MATERIAL: Sixty-three patients,
      haemodynamically stable, were eligible for the study and enrolled into the
      protocol of non-operative management of blunt hepatic injury. Fifty-two (82.5%)
      patients were successfully managed non-operatively (non-operative group). The
      remaining 11 (17.5%) patients failed the non-operative management and underwent
      exploratory laparotomy (laparotomy group). RESULTS: Patients managed non
      operatively tended to be younger than patients managed operatively (p < 0.05).
      The mean values of ISS were 16.2 +/- 6.1, 26.1 +/- 8.5, p < 0.001, in the non
      operative and laparotomy groups, respectively. Stay in the ICU was significantly
      decreased in the non-operative patients (p < 0.001). Patients who had a
      laparotomy significantly increased requirement for blood transfusion (p < 0.001).
      Six (9.5%) patients managed non-operatively developed complications; perihepatic
      collections were observed in two patients, an urinoma in one patient and chest
      infection in three patients. Perihepatic collections and urinoma were
      successfully drained percutaneously by CT guidance and no further treatment was
      required. The mortality rate of the entire series of patients was 4.8% (three
      patients); one death could be related to hepatic injury itself and the other two
      deaths were attributed to non-hepatic causes. No deaths occurred in the non
      operative group. CONCLUSION: Non-operative management should be the initial
      approach to all patients with blunt liver injuries if haemodynamic stability can
      be ensured. When continued bleeding can be safely ruled out, a period of close
      monitoring in the ICU is warranted.

PMID- 15573626
TI  - Expression of E-cadherin in human colorectal cancer.
AB  - AIM: To investigate the expression of E-cadherin, a calcium-dependent cell-cell
      adhesion molecule in colorectal carcinoma. Antibodies to E-Cadherin were used to
      establish the association of their expression with the clinicopathological
      characteristics of this disease using immunohistochemical methods. METHODS:
      Immunohistochemical analysis for E-cadherin was carried out in formalin-fixed,
      paraffin-embedded sections of neoplastic colorectal tissues and non-neoplastic
      ones adjacent to the lesion from 49 patients who underwent surgery, by the
      standard peroxidase-antiperoxidase method. Expression of this antigen in normal
      and malignant epithelium and stromal cells was compared. RESULTS: Both neoplastic
      and normal tissues showed expression of E-cadherin. There was, however, higher
      expression of E-cadherin in epithelial cells in both tumour and normal tissues
      than stromal cells. The percentage of expression in epithelial cells of well
      differentiated tumours was significantly higher than moderately differentiated
      tumours. Loss of normal membranous expression and the presence of cytoplasmic and
      mixed staining were found frequently in tumour tissues (p = 0.004). This loss of
      membranous expression, however, did not correlate with Duke's staging, tumour
      grade, sex, size or site of the tumour. CONCLUSION: This study suggests that the
      lower expression of E-cadherin in less differentiated tumours may explain their
      aggressive nature, although loss of membranous expression was not significantly
      correlated to Duke's staging, tumour grade, sex, size and site of tumour.

PMID- 15573627
TI  - Cholecystectomy in a predominantly African population before and after the advent
      of the laparoscopic technique.
AB  - OBJECTIVE: There is a paucity of information on gallbladder disease in an African
      population. We, therefore, conducted a study to compare the immediate pre
      laparoscopic era with the laparoscopic period in the predominantly African
      population at the King Edward VIII Hospital. MATERIAL AND METHODS: Data from a
      retrospective analysis of 144 patients undergoing open cholecystectomy (OC)
      between January 1990 and December 1992 were compared with a prospective analysis
      of 156 patients who underwent laparoscopic cholecystectomy (LC) between February
      1992 and December 1994. Demographic data, presentation, operative management and
      outcome were the main factors analysed. RESULTS: Eighty-two per cent were Black
      African and the rest of Indian origin. Endoscopic retrograde
      cholangiopancreatography (ERCP) confirmed ductal stones in 11 patients in the OC
      and nine patients in the LC group. Endoscopic duct clearance was achieved in
      three and nine patients, respectively. Non biliary complications were rare. There
      were two major duct injuries in the OC group and one cystic duct leak in the LC
      group. The high conversion rate of 17.9% attests to the severity of their chronic
      disease making safe dissection in Calot's triangle problematic. The mortality in
      patients undergoing OC was 1 (0.07%) and 0% for LC. In South Africa, the hospital
      prevalence of calculous disease in African patients is increasing. However,
      cholecystectomy may be safely performed. CONCLUSION: The absence of any mortality
      and any major duct injury in the LC group allude to the safety of this procedure
      when appropriately applied to this population group.

PMID- 15573628
TI  - Paediatric day-case otoplasty: local versus general anaesthetic.
AB  - BACKGROUND: Correction of prominent ears (otoplasty) is routinely done as an
      elective cosmetic procedure. The operation is typically performed under general
      anaesthesia, which is favoured in the paediatric population, being considered
      more 'humane' than local anaesthesia. AIM: Our aims were to demonstrate the
      feasibility of paediatric otoplasty as a day case procedure and to examine the
      relative efficacy of general versus local anaesthesia, paying particular
      attention to post-operative morbidity. METHODS: Data were gathered
      retrospectively from case notes, day case surgery pro-formas and dressing clinic
      notes to compare post-operative morbidity in the two groups. Specific parameters
      assessed included vomiting, post-operative bleeding, wound dehiscence, necessity
      of overnight stay and need for revision surgery. RESULTS: Eighty-five children,
      underwent a day case otoplasty procedure (age range 4-17 years; mean 7.3). Forty
      four received a general anaesthetic, whilst forty-one received percutaneous
      infiltration of local anaesthetic. Local anaesthetic was well tolerated by the
      children. No procedure was abandoned due to pain. No disadvantage was
      demonstrable in either group by performing the operation as a day case procedure.
      Post-operative vomiting was shown to be a significantly greater problem in the
      children receiving general anaesthesia (p<0.0001). CONCLUSION: Otoplasty as a day
      case procedure appears acceptable whether general or local anaesthesia is used.
      In addition, percutaneous infiltration of local anaesthetic, results in a marked
      reduction in post-operative vomiting without compromising surgical outcome.

PMID- 15573629
TI  - Myths of whiplash.
AB  - When the concept of whiplash was first introduced by Harold Crowe in 1928 at a
      conference, and when it first appeared in a medical publication in 1945, it was
      not based on scientific evidence. That is, like many great stories, the whiplash
      theme sprang mainly from mythology, where many explanations had to be created to
      fill in the gaps in our understanding. Since those early days, and mainly in the
      last ten years, more research has been carried out to unravel these myths than
      had been performed to define chronic whiplash in the first place. This limited
      review considers a few of the aforementioned myths of whiplash, and how
      scientific efforts have enlightened us on these matters.

PMID- 15573630
TI  - The early management of severe tibial pilon fractures using a temporary ring
      fixator.
AB  - BACKGROUND: The management of pilon fractures of the distal tibia is fraught with
      complications. Poor initial management leads to a poorer outcome. Protection of
      the soft tissue envelope is paramount and to achieve this objective early
      fracture reduction, restoration of leg length and elevation are important
      principles in the management of severe injuries. Reduction and restoration of
      length can be achieved through ligamentotaxis by various methods but the most
      commonly employed are calcaneal traction or bridging external fixation.
      OBJECTIVE: We describe our method for the early management of these injuries
      using a simple semicircular bridging frame.

PMID- 15573631
TI  - MRSA infected pseudoaneurysms of the radial artery.
AB  - The use of radial artery catheters for real-time blood pressure monitoring and
      arterial blood gas sampling has become commonplace in both intensive care and
      high dependency units. Although this procedure is relatively safe, it can be
      complicated by local infection leading to pseudoaneurysm formation. In this
      report we describe three cases of pseudoaneurysm formation following prolonged
      radial catheter placement, with evidence of local methicillin resistant
      staphylococcus aureus (MRSA) infection. With the growing problem of in-hospital
      MRSA colonisation, the report aims to emphasize the need for vigilance for this
      complication and reinforce the importance of careful asepsis. In all cases the
      pseudoaneurysms were successfully treated with local ligation of the radial
      artery, without subsequent ischaemic complications. Allen's test was performed to
      ensure sufficient collateral circulation prior to surgery.

PMID- 15573632
TI  - Flame bums: a forgotten danger of diathermy?
AB  - Diathermy and spirit-based skin preparations are both used on a daily basis in
      most hospital theatres. We report a case illustrating the potential hazards of
      this combination and discuss the management of its complications and
      possibilities of their prevention.

PMID- 15573633
TI  - Complete rectal obstruction due to ischaemia following elective abdominal aortic
      aneurysm surgery.
AB  - Ischaemic rectal stricture formation is a rare but documented complication of
      aortic aneurysm surgery. We report the first case of acute large bowel
      obstruction secondary to this rare complication.

PMID- 15573634
TI  - A unique complication of ureterosigmoidostomy: a chance encounter with a rectal
      stone.

PMID- 15573635
TI  - Re: "An alternative approach to fishbone extraction" by R. Viney and A. Reid J R
      Coll Edinb 2002; 47:515.

PMID- 15573636
TI  - Re: "Wandering spleen: case report and literature review" Satyadas et al. J R
      Coll Edinb 2002; 47: 512-514.

PMID- 15573637
TI  - Re: "Wandering spleen: case report and literature review" Satyadas et al. J R
      Coll Edinb 2002; 47: 512-514.

PMID- 15573638
TI  - Re: "Fireworks injury: temporal bone penetration and a wooden intra-cranial
      foreign body" by A. Al Mulla, M. Purva and A. Behbehani, J R Coll Surg Edinb 46.4
      249-251.

PMID- 15573639
TI  - Re: "Predictors of excessive blood loss during operative treatment of hip
      fractures" Odumala et al. J R Coll Edinb 2002; 47: 552-556.

PMID- 15573640
TI  - Cocamidopropyl betaine.

PMID- 15573641
TI  - Allergy to cocamidopropyl betaine and amidoamine in North America.
AB  - BACKGROUND: The prevalence of allergy to cocamidopropyl betaine (CAPB) in North
      America has not been previously reported. OBJECTIVE: The aim of this study was to
      report on the most recent data on allergy to CAPB and a related allergen,
      amidoamine (AA). METHODS: Data was collected by the North American Contact
      Dermatitis Group from consecutive patients presenting for patch testing for
      diagnosis of presumed allergic contact dermatitis (ACD) from January 1, 2001,
      through December 31, 2001. RESULTS: Of 975 patients tested, 15 were patch-test
      positive to CAPB, 25 had positive reactions to AA, and 18 had positive reactions
      to both CAPB and AA. The most frequent site of dermatitis from CAPB was the head
      and neck region. CONCLUSION: In North America, both CAPB and AA are useful
      allergens for detecting ACD.

PMID- 15573642
TI  - Relevance of positive patch-test reactions to cocamidopropyl betaine and
      amidoamine.
AB  - BACKGROUND: Cocamidopropyl betaine (CAPB) is a surfactant, primarily used in
      personal cleansing products, that may cause allergic contact dermatitis (ACD).
      Amidoamine (AA), a by-product and a known contaminant in CAPB synthesis, may be
      the true allergen responsible for some cases of CAPB allergy. Co-reactivity with
      these allergens and cocamide diethanolamine (CDEA) and formaldehyde has been
      noted anecdotally. OBJECTIVE: This study investigated (1) the correlation and
      clinical relevance of positive patch-test reactions to CAPB and AA in cases of
      ACD and (2) the rate of positive reactions to CDEA and formaldehyde in these
      patients. METHODS: Patients with patch-test reactions to either CAPB or AA during
      2001 were retrospectively identified. Relevance of reactions to CAPB and AA was
      then graded as definite, probable, or not relevant, based on patient follow-up.
      The proportion of these patients who also had positive reactions to CDEA or
      formaldehyde was noted. RESULTS: Of 957 patch-tested patients, 49 had positive
      reactions to either CAPB (42.9%) or AA (34.3%) or to both (22.8%). Of these
      patients, 35 were available for follow-up. Twenty-nine (83.0%) of these patients
      identified the surfactant in their home products. In all of these patients, the
      dermatitis was felt to be due in whole or in part to CAPB exposure. Two patients
      (5.7%) had a positive reaction to CDEA, and 8 patients (23%) had a positive
      reaction to formaldehyde. CONCLUSION: Patch testing with both CAPB and AA
      identifies patients with ACD relevant to exposure to CAPB. Since few patients
      react to both allergens, testing with both separately is useful. Formaldehyde
      allergy was overrepresented in CAPB-allergic patients in this series of patients.

PMID- 15573643
TI  - Effectiveness of a hand care regimen with moisturizer in manufacturing facilities
      where workers are prone to occupational irritant dermatitis.
AB  - BACKGROUND: Limited information documents the prevention and treatment benefits
      of a hand care regimen using moisturizer in a controlled manner for employees in
      typical manufacturing situations. OBJECTIVE: The objective was to assess the
      effectiveness of a comprehensive skin care program including skin conditioning
      lotion in multiple manufacturing environments where employees are at high risk
      for skin disease. METHODS: A randomized trial test design with multiple measures,
      including skin bioengineering measurement techniques, visual grading, and self
      assessment questionnaires, was used to broadly characterize skin condition.
      RESULTS: Comparison of the change in the skin condition of workers using the full
      hand care regimen with moisturizer versus a control group using a regimen without
      moisturizer demonstrated significant (p < .05) improvements in multiple measures
      after 1 to 2 weeks. Corneometer readings consistently showed significant
      improvement for employees using moisturizer, regardless of their work location.
      CONCLUSION: Improved skin condition resulted from the regular use of an effective
      skin conditioning hand moisturizer as part of a skin care regimen in work
      environments in which workers were prone to experiencing occupational irritant
      contact dermatitis.

PMID- 15573644
TI  - Health care services use by workers with work-related contact dermatitis.
AB  - BACKGROUND: There is little information in the literature regarding the use of
      health care services by workers with occupational contact dermatitis. OBJECTIVE:
      The objective of the study was to describe the use of health care services by
      workers with occupational contact dermatitis. METHODS: One hundred workers with
      hand dermatitis were enrolled and observed for 6 months after assessment at St.
      Michael's Hospital (Toronto, ON, Canada). Information was collected at the time
      of diagnosis and 6 months after the assessment. Questionnaires were administered
      to collect information about clinical presentation and the use of health
      services. RESULTS: A diagnosis of occupational contact dermatitis was made for 78
      of the workers. By the time of assessment at the Occupational Health Clinic at
      St. Michael's Hospital, almost all of the workers had seen their family doctor
      for their skin problem, and 71% had seen a dermatologist. Although family doctors
      and dermatologists asked the workers to identify their occupation, they rarely
      asked about workplace exposures, and the physicians provided minimal advice about
      job change or modification on return to work. During the 6 months following
      diagnosis, 62% of the workers saw their family physicians in follow-up, but
      rarely was advice about job change or modification provided at these follow-up
      visits. CONCLUSIONS: This descriptive information suggests that there are gaps in
      health services for patients with work-related skin disease and that there is a
      need for refinement of the delivery of health services related to occupational
      disease. A redesign of the occupational health care delivery system to address
      these issues and an evaluation of new models seem appropriate.

PMID- 15573645
TI  - Etiology of hand dermatitis among patients referred for patch testing.
AB  - BACKGROUND: Hand dermatitis affects many people and has numerous causes. Few
      reports have looked at the etiology of hand dermatitis across broad demographics.
      OBJECTIVES: The purposes of this investigation were to (1) determine the causes
      of hand dermatitis in the population patch-tested at a dermatologic referral
      clinic, (2) report occupations frequently associated with hand dermatitis, and
      (3) indicate which substances were the more common allergens among individuals
      evaluated by patch testing for hand dermatitis. METHODS: A retrospective analysis
      of patch-test data on 1,034 patients who were evaluated during an 8-year period
      was performed. RESULTS: Hand dermatitis affected 32% of all patients who
      underwent patch testing. Allergic contact dermatitis was diagnosed most often
      (54.4%), followed by irritant contact dermatitis (27.4%). Among women, irritant
      contact dermatitis of the hands peaked in the third decade and then diminished
      whereas allergic contact dermatitis of the hands remained fairly constant among
      patients between 21 and 60 years of age. In contrast, irritant contact dermatitis
      and allergic contact dermatitis in men peaked in the fifth decade of life. In
      both genders, hand dermatitis was rare among those 20 years of age or younger and
      among those 61 years of age or older. Fifty-six percent of hand dermatitis was
      related to occupation. Health care workers were most often affected by
      occupational hand dermatitis. The most common allergens for both occupational and
      non-occupational hand dermatitis were quaternium-15, formaldehyde, thiuram mix,
      and carba mix. CONCLUSIONS: Since more than half of hand dermatitis cases may be
      related to occupation, a thorough history should be taken by a knowledgeable
      clinician. Potentially relevant allergens in the workplace must be identified and
      tested. These allergens may not be contained in standard trays.

PMID- 15573646
TI  - Epoxy-based production of wind turbine rotor blades: occupational contact
      allergies.
AB  - BACKGROUND: An industry producing rotor blades for wind turbines with an epoxy
      based technology had experienced an increasing number of workers with dermatitis,
      among whom the frequency of occupational contact allergy (OCA) was suspected to
      be underestimated. OBJECTIVE: To investigate the frequency of OCA by patch
      testing with a specially profiled occupational patch test series. METHODS: In a
      blinded study design, 603 workers were first interviewed and thereafter
      clinically examined. Based on a history of work-related skin disease, clinical
      findings of dermatitis, or both, 325 (53.9%) of the workers were patch-tested
      with an occupational patch test series and the European Standard patch test
      series. RESULTS: Of the 603 investigated workers, 10.9% had OCA and 5.6% had
      contact allergy to epoxy resin in the standard test series. Contact allergy to
      amine hardeners/catalysts was found in 4.1% of the workers. Among the workers
      with OCA, 48.5% reacted to work material other than epoxy resin in the European
      Standard patch test series. CONCLUSION: Approximately 50% of the workers with OCA
      would not have been detected if only the European Standard patch test series had
      been used.

PMID- 15573647
TI  - Occupational contact dermatitis from a grease.
AB  - BACKGROUND: Contact allergy to grease is rare and often not even suspected. We
      investigated such a case in which the detected allergen was the stabilizer in the
      grease, which is rarely found as an allergen. OBJECTIVE: Thin-layer
      chromatography (TLC) was used in a novel way and helped detect the allergen.
      METHODS: Patch testing with our standard series, a metal-working series, the
      different substances individually, the grease in serial dilution and extracts of
      personal objects, the TLC plate. Gas chromatography-mass spectrometry was also
      used. RESULTS: Test results indicated contact allergy to grease containing N
      phenyl-1-naphthylamine and contact allergy to Disperse Orange 1, N-cyclohexyl-N'
      phenyl-4-phenylenediamine, N-isopropyl-N'-phenyl-4-phenylenediamine, and N,N'
      diphenyl-4-phenylenediamine. CONCLUSION: N-phenyl-1-naphthylamine was the main
      cause of the patient's dermatitis. This case report underlines the importance of
      testing the patient's own products and also underlines the benefit of using TLC
      strips for patch testing and of visiting the workplace to get correct information
      about exposure conditions.

PMID- 15573648
TI  - Allergic contact dermatitis from chlorhexidine.
AB  - Although chlorhexidine is a widely used substance, allergic contact dermatitis
      from chlorhexidine has rarely been reported. Our objective was to study all cases
      of allergic contact dermatitis from chlorhexidine that were seen at St John's
      Institute of Dermatology from January 1983 to June 2002. The case records of all
      patients with positive patch-test reactions to chlorhexidine during the study
      period were retrieved. The clinical presentation, strength, and relevance of the
      positive patch-test results as well as possible sources of exposure were studied.
      There were five cases of allergic contact dermatitis from chlorhexidine during
      the study period; three of these patients had positive patch-test reactions to
      chlorhexidine that were of current relevance. The possible sources of exposure
      included Hibisol, Hibiscrub, a chlorhexidine spray, and peri- and postoperative
      antiseptic solutions. We concluded that allergic contact dermatitis from
      chlorhexidine is rare. However, when it occurs, it may cause a severe dermatitis
      reaction.

PMID- 15573649
TI  - Allergic contact dermatitis from hearing aid materials.
AB  - A 65-year-old woman presented with dermatitis of the ear canal. The dermatitis
      had developed after she started wearing hearing aids that fit into the ear
      canals. Patch-test results were positive for (1) several acrylics, including
      polyethylene glycol dimethacrylate and 2-hydroxyethyl methacrylate, which were
      present in the hearing aid shell; (2) the hearing aid shell materials; and (3)
      the finish coat. The dermatitis resolved after she discontinued wearing the
      hearing aid, and a device with a silicone earpiece to be worn behind the ear was
      recommended as an alternative.

PMID- 15573650
TI  - Allergic contact dermatitis from acrylates in artificial nails.
AB  - Artificial nails are an increasingly popular cosmetic enhancement to the natural
      nail. Several forms are available, including sculptured nails, photobonded nails,
      and preformed nails. Reactions to artificial nails have included paronychia,
      onychodystrophies, and dermatitis at contact areas and at sites distant to the
      contactant. We present a patient who developed erythema and painful pruritic
      vesicles of the paronychial tissue several hours after the application of
      sculptured nails. A strong reaction of erythema and edema occurred at the site of
      methyl methacrylate and ethylene glycol dimethacrylate testing. Removal of the
      artificial nails resulted in resolution of the reaction.

PMID- 15573651
TI  - Allergic contact dermatitis due to amorolfine nail lacquer.

PMID- 15573652
TI  - Allergic contact dermatitis from dibutylthiourea in a wet suit.

PMID- 15573653
TI  - The prevalence and pattern of nursing caries in preschool children of Tehran.
AB  - This cross sectional study was carried out to determine the prevalence and
      pattern of nursing caries and its relevant factors in preschool children of
      Tehrari. 620 children aged 2-6 yrs were selected randomly from 22 kindergartens
      in Tehran. They were examined for dental caries. The criteria used for nursing
      caries was presence of caries on buccal or palatal surfaces of at least two
      maxillary incisors with absence of caries in mandibular incisors. A questionaire
      was used for evaluation of related factors.

PMID- 15573654
TI  - "Moebius syndrome": a case report.
AB  - Moebius syndrome is an extremely rare disorder characterized by a lifetime facial
      paralysis, involving sixth and seventh cranial nerves with malformations of
      orofacial structures and the limbs. In this case, an 8 year old girl with Moebius
      syndrome is presented, clinical findings are described and management aspects are
      discussed. Early dental evaluation and parental counselling as a part of
      preventive dental regimen can go a long way in providing complete psychosocial
      rehabilitation for such physically disabled children.

PMID- 15573655
TI  - Evaluation of an alum-containing mouthrinse for inhibition of salivary
      streptococcus mutans levels in children--a controlled clinical trial.
AB  - The anticariogenic effect of alum was evaluated in the study by measuring the
      salivary S. mutans levels of children at baseline, after 3-weeks, and 6-weeks of
      using alum-containing mouthrinses. Sixty subjects with a mean age of eleven years
      were selected and randomly divided into four groups. Two experimental mouthrinses
      (alum in physiological saline and alum in distilled water) and two control
      mouthrinses (physiological saline and distilled water) were given for a period of
      6 weeks on a daily basis. Salivary samples were collected at the end of 3 weeks
      and 6 weeks and S. mutans levels were assessed and compared with baseline values
      and among each other. Both the alum-containing mouthrinses produced statistically
      significant reductions in S. mutans levels in children, thus tempting us to
      announce alum as a routine oral hygiene measure, though its safety for prolonged
      usage needs to be established by long-term studies.

PMID- 15573656
TI  - Central giant cell granuloma in child: a case report.
AB  - The central giant cell granuloma or CGCG is a benign intraosseous lesion of the
      jaw. It is found predominantly in children and young adults. A case of 10 year
      old male child with CGCG in mandible is presented.

PMID- 15573657
TI  - Efficacy and acceptabilty of oral-transmucosal midazolam as a conscious sedation
      agent in pre-school children.
AB  - The purpose of the present study was to test the efficacy of oral-transmucosal
      route of administration of midazolam in young potentially un-cooperative
      children. A sample of 40 children up to 4 years of age with ASA I status were
      randomly divided into experimental and control groups of 20 each. The children in
      experimental group received 0.5-mg/kg-body weight midazolam mixed in strawberry
      syrup via the oral-transmucosal route and those in control group were given the
      same syrup diluted with normal saline. A class II amalgam restoration was
      performed and routine behavior management techniques were employed in both
      groups. It was found that the number of procedures successfully completed and
      sedation produced 15 minutes after test solution administration was significantly
      greater in the experimental group compared to the control group. The total
      treatment time was also much lesser in the experimental group children. There was
      no significant difference in the acceptability of the test solutions in the
      children of the two groups.

PMID- 15573658
TI  - A compound composite odontoma associated with unerupted permanent incisor--a case
      report.
AB  - Odontomas are the most common type of odontogenic tumors and generally they are
      asymptomatic. Frequently it may interfere with the eruption of the teeth. This is
      a case report of a compound composite odontoma in a 9 year old girl, which
      results in failure of eruption of the permanent upper right central incisor while
      the contralateral tooth had erupted. A calcified mass was seen in the radiograph
      and was provisionally diagnosed as odontoma following which the odontoma was
      enucleated. Routine follow up was done for more than a year and no recurrence was
      seen. This case report indicates that early diagnosis and management ensures
      better prognosis.

PMID- 15573659
TI  - Dental erosion in children : an increasing clinical problem.
AB  - Epidemiological studies carried out on dental erosion have established that the
      prevalence is high in young people and adolescents. The objective of this study
      was to look at the prevalence and etiology of dental erosion, particularly in
      children, and its practical management for its possible control. The children
      between 5-6 yrs were examined and findings recorded, and this study has shown
      that approximately 1/3rd of 5-6 yrs old children have appreciable tooth wear and
      dental erosion.

PMID- 15573660
TI  - Management of two unusual cases of dens invaginatus and talon cusp associated
      with other dental anomalies.
AB  - The management of two unusual cases of dens invaginatus and talon cusp is
      presented. The first concerns talon cusp in maxillary primary and permanent
      lateral incisors, a supplemental tooth with dens invaginatus hampering eruption
      of the permanent incisors. The other present with bizarre crown morphology of a
      lateral incisor with talon cusp, dens invaginatus and a palatal accessory cusp
      like structure. Early diagnosis and management are important to avoid
      complications.

PMID- 15573661
TI  - Band and loop space maintainer--made easy.
AB  - Space maintainers have been used in Pediatric Dentistry for many years. The use
      of these appliances, however, in terms of indications, contraindications, design
      and construction has gained little attention from researchers. This paper
      highlights the construction of a new technique of fabrication of band and loop
      space maintainer. The advantages of this new Direct technique or Single sitting
      technique over the conventional technique are discussed.

PMID- 15573662
TI  - Maxillo- mandibular relationship--a cephalometric study.
AB  - An accurate assessment of apical base relationships using cephalometrics has been
      a perennial problem in orthodontics. The currently available literature suggests
      that reference points and planes are subject to change with treatment. Hence, an
      assessment of sagittal jaw relationship was done using five angular measurements
      and an attempt was made to determine the one which is statistically more
      accurate.

PMID- 15573663
TI  - Hereditary opalescent dentin--a case report.
AB  - A female patient aged 6 years reported with brown coloured small sized teeth that
      were continuously wearing out. The teeth were badly attrited upto the gingival
      margins. The occlusal surfaces were flattened. The clinical and radiographical
      examination confirmed the case as Hereditary opalescent Dentin. The rationale for
      early diagnosis and treatment has been discussed.

PMID- 15573664
TI  - The knowledge, approach and function of pediatricians in prevention of caries in
      Tehran.
AB  - The Study was carried out an 160 Pediatricians in Tehran to find out the
      knowledge, approach and functioning of the pediatricians as related to the
      awareness regarding prevention of dental Caries. It was observed that 14.4% of
      the pediatricians had good dental awareness, 48.1% had moderate awareness and
      37.5% had weak awareness.

PMID- 15573665
TI  - "Craniofacial and dental manifestations of a case of Proteus syndrome".
AB  - Proteus syndrome, which is a reference to the ancient Greek god Proteus, the
      Polymorphous, was called to the attention of pediatricians. Recognition of this
      syndrome has been difficult because of the variability of the syndrome's
      manifestations and because of its rarity. We describe a rare case of Proteus
      syndrome and we discuss its differential diagnosis. Our case presents with hemi
      facial hypertrophy, scrotal tongue, enamel hyperplasia as well as differential in
      the size of the dentition on both sides of the arch.

PMID- 15573666
TI  - Periapical repair and apical closure of a pulpless tooth using calcium hydroxide-
      a case report.
AB  - A case with a open apex and a large periapical lesion in a 10 year old boy is
      presented. The lesion formed as a result of necrosis from trauma to a maxillary
      right central incisor 1 year ago. Apical closure and complete healing of
      periapical lesion was observed after non-surgical endodontic treatment using
      calcium hydroxide paste. This report suggests that even large periapical lesions
      could respond favourably to non-surgical treatment.

PMID- 15573667
TI  - The changing landscape: Kansans near the end of life.

PMID- 15573668
TI  - Palliative care: the development of clinical practice guidelines.

PMID- 15573669
TI  - Trends in hospice and palliative care in the United States and Kansas.

PMID- 15573670
TI  - The Alliance for Excellence in Hospice and Palliative Nursing.

PMID- 15573671
TI  - Merriam--a good death.

PMID- 15573672
TI  - Clinical practice guidelines for quality palliative care.

PMID- 15573673
TI  - EPSDT & billing.

PMID- 15573674
TI  - Evidenced-based practice.

PMID- 15573675
TI  - [Alcohol dependence syndrome and BDIM (before-discharge intervention method)-
      Report 3. The patients' self-reports about BDIM].
AB  - The purpose of this study is to identify how the effects of BDIM are evaluated by
      patients who were practiced BDIM. 153 patients were treated by the structured
      BDIM (Before-Discharge Intervention Method) program. Among them, 82 patients
      (53.6%) have attended self-help group meetings or maintained the therapeutic
      relationship (as outpatients or inpatients) in the 4 months' study period. To
      identify the maintenance of the effects of BDIM, we made our questionaire that
      consist of the patients' choice of answer and the patients' self-reporting. 76 of
      82 patients answered our questionaire. After 76 patients discharged from
      hospital, 4 1/3 years have passed on the average. Their positive answers are as
      follows. (1) I became aware that my drinking had bad effect on my beloved family.
      (2) I became aware that my family have kept compassion, expectation and
      appreciation for me. Their message treated me and strengthened my self-esteem. In
      addition, I accepted the reality of my drinking problems. (3) I recognized all my
      family members want my abstinence and functional communication. (4) I was
      extremely impressed by my family members' tears. Their tears made me decide
      strong abstinence. (5) I was empowered by my family members. Through BDIM, I felt
      a sense of security, self-esteem and freedom. (6) I thought that BDIM was a good
      treatment program. And I thought that the application of letters is useful to
      recover the patients from alcohol dependence syndrome. Their negative answers are
      as follows. (1) I thought it was impossible for me to be abstinent. (2) I
      couldn't keep the motivation of abstinence. (3) I thought BDIM was a negative
      treatment method. Some findings of this study are as follows: First, the letters
      which was handed from family members to the patient were read again and again,
      also preserved with much care. Therefore we get know that BDIM is useful for the
      patient to get and remember some good memories of the family members for a long
      time. Second, BDIM is helpful for the patients to become aware of their own
      drinking problems and realize the necessity of recovery.

PMID- 15573676
TI  - [Adult fetal alcohol syndrome (FAS) with various nouropsychiatric symptoms].
AB  - This is the first report of an adult patients with the fetal alcohol syndrome
      (FAS) in Japan, who was treated for psychiatric disorders. The case was a 35
      years-old woman who had many neuropsychiatric symptoms. She had been treated for
      15 years at the Kurihama Alcoholism Center, for mental retardation, schizophrenic
      symptoms, attention deficit hyperactivity disorder, learning disorder,
      trichotillomania, bipolar disorder, and impulsive behavior. She had low body
      weight at birth, mental retardation and a small facial malformation, which were
      diagnosed as FAS. At first admission, she was not diagnosed as FAS because her
      parent denied that her mother drank during pregnancy. Recently, her family
      admitted her mother's heavy drinking during pregnancy, and we diagnosed her as
      having FAS. She showed many pathological symptoms of the central nervous system
      such as very lower scores for performance IQ than for verbal IQ in the WAIS-R and
      enlargement of the lateral ventricle on MRI. Recently many reports have mentioned
      that prenatal alcohol exposure brings about severe damage of the central nervous
      system. Therefore, one author proposes that such disorders are referred to as
      fetal alcohol spectrum disorders (FASD). This patient showed many symptoms of
      FASD, and was difficult to treat because of these symptoms.

PMID- 15573677
TI  - [Case report of pentazocine dependence from a standpoint of the cognitive
      therapy].
AB  - Drug dependence is a social problem of over the world and resistant to medical
      intervention by psychiatrist as well as general clinicians. In Japan,
      methamphetamine dependence is one of the most critical social problems, but
      opioid dependence is relatively rare. Pentazocine was called the non-addictive
      opioid at the time of development and release and there are few reports of its
      dependence. We experienced a medical worker with pentazocine dependence. He
      started to use pentazocine to reduce serious migraine and felled into dependence
      by changing the purpose to relaxation of stammering fear and strain towards other
      people. He was successfully treated by cognitive therapy.

PMID- 15573678
TI  - Perspectives. States at bottom of public-health rankings slip further behind.

PMID- 15573679
TI  - Reshaping radiology: change management and workflow optimization give PACS new
      punch.

PMID- 15573680
TI  - Electronic follow-up: bar coding and RFID both lead to significant goals-
      efficiency and safety.

PMID- 15573681
TI  - Thoughts from the IT Czar. Public funds are needed for a national health network.

PMID- 15573682
TI  - Web technology in managed care: use it as the workhorse it can be.

PMID- 15573683
TI  - Shotgun innovation: under 'Mark Z,' El Camino's famed inventiveness heads into
      hyperdrive.

PMID- 15573684
TI  - Automation in cancer care: even sophisticated technology finds the treatment as
      perplexing as the disease.

PMID- 15573685
TI  - The HIPAA training challenge: customized e-learning helps staff pass the test.

PMID- 15573686
TI  - Effect of piroxicam on matrix metalloproteinase 2 and apoptosis.
AB  - We examined the effect of a nonsteroidal anti-inflammatory drug (NSAID),
      piroxicam, on apoptosis and matrix metalloproteinase 2 (MMP-2) activity compared
      with diclofenac and dexamethasone. The fibrosarcoma (WEHI-164) cell line was used
      to assess tolerability, MMP-2 activity and apoptosis. Piroxicam, dexamethasone
      and diclofenac were used at concentrations of 10-200 microg/ml in triplicate and
      2-fold dilutions. MMP-2 activity was assessed using zymography. For assessment of
      apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) method was used. The results of this study show that piroxicam
      is able to diminish MMP-2 activity and induce apoptosis under in vitro
      conditions. Piroxicam also showed high tolerability compared with diclofenac and
      dexamethasone. In conclusion, piroxicam is able to induce apoptosis and suppress
      MMP-2 activity.

PMID- 15573687
TI  - The effects of hyaluronan on bone resorption and bone mineral density in a rat
      model of estrogen deficiency-induced osteopenia.
AB  - Hyaluronan, or hyaluronic acid (HA), is an essential component of extracellular
      matrices. HA of appropriate molecular weight and concentration can induce
      osteoblast differentiation and bone formation in vitro. The aim of our study was
      to evaluate the effects of HA of different molecular weights on ovariectomy (OVX)
      induced bone loss in rats. Adult female Sprague Dawley rats were subjected to
      bilateral OVX or sham surgical procedure (sham). OVX rats were treated with: HA
      of molecular weight of 0.75 MDa at a dose of 1 mg/kg/day and with HA of molecular
      weight of 1.62 MDa at a dose of both 0.5 mg/kg/day and 1 mg/kg/day. HA was
      applied orally once a day during the 8-week period after ovariectomy. Body
      weight, urinary pyridinoline (Pyr), deoxypyridinoline (DPyr) corrected for
      urinary creatinine, serum nitrite/nitrate concentrations and whole body and
      femoral bone mineral density (BMD) were measured. HA treatment had no effect on
      the body weight gain in OVX rats. Excretion of urinary Pyr and Dpyr significantly
      increased in OVX rats compared to sham controls. The higher molecular weight HA
      (1.62 MDa) significantly reduced urinary Pyr and DPyr concentrations measured on
      day 28 after ovariectomy (p < 0.001). Serum concentrations of nitric oxide
      metabolites, nitrite/nitrate significantly decreased in OVX rats in comparison
      with sham controls (p < 0.001). HA of both 0.75 MDa and 1.62 MDa molecular
      weights significantly enhanced serum nitrite/nitrate concentrations in OVX rats.
      There was a clear reduction of whole body and femoral BMD in untreated OVX rats.
      The higher molecular weight HA decreased both whole body and femoral BMD loss.
      Our results show that orally applied HA of high molecular weight (1.62 MDa)
      inhibits bone resorption and provides a protective effect on bone density in
      ovariectomized rats.

PMID- 15573688
TI  - A randomized comparison of nail surface remanence of three nail lacquers,
      containing amorolfine 5%, ciclopirox 8% or tioconazole 28%, in healthy
      volunteers.
AB  - This randomized, investigator-masked study compared the remanence on the nail
      surface of commercially available antimycotic nail lacquers containing
      amorolfine, ciclopirox and tioconazole. The lacquers, to which a coloring agent
      was added, were applied randomly to the left and right thumbnails and great
      toenails of 10 healthy volunteers. Volunteers were asked to wash their hands
      under standardized conditions at 30, 60 and 90 min after product application and
      to take at least one shower during the study. Photographs were taken immediately
      after drug application and at 30, 60 and 90 min, i.e., immediately after each
      hand washing, and then at 8 and 24 h. Photographs of treated toenails were taken
      at 0, 8 and 24 h. Photographic image analysis allowed automatic calculation of
      the proportion of nail surface remaining covered by the different nail lacquers
      over time and after washing. In addition, clinical visual assessment was made to
      determine the degree of the nail surface covered by the nail lacquers over time.
      It was demonstrated that at 24 h after product application, remanence of
      amorolfine nail lacquer on the thumbnails was significantly higher than that of
      ciclopirox (p < 0.05) and that of tioconazole on the thumb- and toenails at each
      time point up to 8 h after product application (all p < 0.05). Clinical
      observation showed that 30 min after application, the tioconazole nail lacquer
      had still had not completely dried. Amorolfine nail lacquer was shown to be more
      resistant than ciclopirox and tioconazole nail lacquers to chemical trauma from
      soaps and to mechanical aggressions from the immediate nail environment.

PMID- 15573689
TI  - Scleredema of Buschke: remission with factor XIII treatment.
AB  - We describe the case of a 55-year-old man with scleredema of Buschke of the torso
      complicated by insulin-dependent diabetes mellitus. Due to (i) the patient's poor
      general health status, (ii) the similarity between scleroderma and scleredema of
      Buschke, and (iii) the well known efficacy of factor XIII infusions in
      scleroderma, we attempted an intravenous treatment with factor XIII. This therapy
      resulted in marked increase of movements and in softening of the skin, together
      with ultrasonographic and histopathological improvements. In conclusion, to the
      best of our knowledge, this is the first case in which factor XIII has been
      successfully used for the treatment of scleredema of Buschke.

PMID- 15573690
TI  - Very low level laser therapy attenuates edema and pain in experimental models.
AB  - In this study, we tested a new square wave microprocessor-controlled red laser
      with an extremely low peak power output (<3 mW; very low level laser therapy
      [vLLLT]) in experimental pain in the rat. Acute inflammation was induced by
      intraplantar injection of carrageenan, chronic inflammation was induced by
      complete Freund's adjuvant (CFA) and neuropathic pain was produced by sciatic
      nerve chronic constriction injury (CCI). In our study vLLLT was effective in
      reducing edema and hyperalgesia in acute and chronic inflammation if administered
      at the points usually selected for acupuncture. Moreover, spontaneous pain and
      thermal hyperalgesia were reduced in CCI rats treated with vLLLT In conclusion,
      vLLLT reduced edema and induced analgesia in experimental plantar pain in rats.
      We interpret this to mean that enkephalin mRNA level was strongly upregulated in
      the external layers of the dorsal horn of the spinal cord in CFA and CCI animals,
      and that vLLLT further increased the mRNA level in single neurons.

PMID- 15573691
TI  - Joint involvement patterns in nodal versus erosive osteoarthritis of the hands.
AB  - The aim of this study was to evaluate the joint count for affected joints and
      involvement distribution in erosive osteoarthritis (EOA) versus nodal
      osteoarthritis (NOA) of the hands in patients matched for sex, age, and disease
      duration. After recruitment of 101 consecutive outpatients affected with EOA, 101
      patients affected by NOA were selected and matched for age, sex, and disease
      duration. Joint count for distal interphalangeal (DIP), proximal interphalangeal
      (PIP), and first carpo-metacarpal (CMC-1) joints, presenting Kellgren and
      Lawrence grade 2-4 OA, was performed. In our study, the number of affected joints
      was higher in NOA, with significant differences for some articular districts,
      especially in PIP joints of the fourth finger, and DIP joints of the second,
      third and fourth fingers.

PMID- 15573692
TI  - Anti-inflammatory activities of Aller-7, a novel polyherbal formulation for
      allergic rhinitis.
AB  - Allergic rhinitis is an immunological disorder and an inflammatory response of
      nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs
      when the body overreacts to a substance such as pollens or dust. A novel, safe
      polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of
      allergic rhinitis using a unique combination of extracts from seven medicinal
      plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica,
      Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since
      inflammation is an integral mechanistic component of allergy, the present study
      aimed to determine the anti-inflammatory activity of Aller-7 in various in vivo
      models. The efficacy of Aller-7 was investigated in compound 48/80-induced paw
      edema both in Balb/c mice and Swiss Albino mice, carrageenan-induced paw edema in
      Wistar Albino rats and Freund's adjuvant-induced arthritis in Wistar Albino rats.
      The trypsin inhibitory activity of Aller-7 was also determined and compared with
      ovomucoid. At a dose of 250 mg/kg, Aller-7 demonstrated 62.55% inhibition against
      compound 48/80-induced paw edema in Balb/c mice, while under the same conditions
      prednisolone at an oral dose of 14 mg/kg exhibited 44.7% inhibition. Aller-7
      significantly inhibited compound 48/80-induced paw edema at all three doses of
      175, 225 or 275 mg/kg in Swiss Albino mice, while the most potent effect was
      observed at 225 mg/kg. Aller-7 (120 mg/kg, p.o.) demonstrated 31.3% inhibition
      against carrageenan-induced acute inflammation in Wistar Albino rats, while
      ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller-7 also exhibited a
      dose-dependent (150-350 mg/kg) anti-inflammatory effect against Freund's adjuvant
      induced arthritis in Wistar Albino rats and an approximately 63% inhibitory
      effect was observed at a dose of 350 mg/kg. The trypsin inhibitory activity of
      Aller-7 was determined, using ovomucoid as a positive control. Ovomucoid and
      Aller-7 demonstrated IC50 concentrations at 1.5 and 9.0 microg/ml, respectively.
      These results demonstrate that this novel polyherbal formulation is a potent anti
      inflammatory agent that can ameliorate the symptoms of allergic rhinitis.

PMID- 15573693
TI  - Multiple effects of theobromine on fetus development and postnatal status of the
      immune system.
AB  - Caffeine and its active derivative, theobromine, are probably the most frequently
      ingested pharmacologically active substances. Considering their uninhibited
      transport via the placental barrier as well as immature enzymatic activities and
      metabolic pathways in embryos and infants resulting in the longer half-life of
      methyloxanthines and their accumulation, unrestrained uptake of these substances
      might result in noticeably more pronounced biological effects during pregnancy
      and the postnatal period. Our previous studies have shown that methyloxanthines
      are significant inhibitors of angiogenic growth factors production and
      angiogenesis itself. We have hypothesized that increased uptake of these
      substances might affect embryonal angiogenesis and, later in the postnatal
      period, maturation and functional activity of the offspring's immune system. The
      study was performed on 2-month-old Balb/c mice fed theobromine 2 or 6 mg/day
      during pregnancy and lactation. On day 18 of pregnancy the number and weight of
      embryos were assessed as was their tissue angiogenic activity, using the
      cutaneous angiogenesis assay. In the group of 4-week-old sucklings, body and
      spleen were weighed together with the trunk, and tail and limb length were
      measured. Six weeks after birth the splenocytes' mitogen-induced activity and
      their ability to induce graft-versus-host reaction as well as the humoral
      response to SRBC antigen were evaluated. Content of theobromine in the embryos'
      tissue was estimated by high liquid performance chromatography (HPLC).
      Theobromine feeding resulted in significant inhibition of embryo growth as
      assessed by their weight and decreased angiogenic activity of their tissue. The
      theobromine content in embryo tissue from treated groups was higher than in the
      controls, and the difference was close to significant. In the postnatal period
      the discrepancies in the treated 4-week-old group's development were also
      observed in the significantly shorter limbs in comparison to the controls.
      Moreover in the treated group of 6-week-old sucklings, considerable variations in
      the immune system's functional activity were registered as far as cellular and
      immune response were concerned. Respectively, the splenocytes' mitogen-induced
      proliferative activity was significantly suppressed while the graft-versus-host
      reaction was up-regulated, and the serum antibodies titer was elevated in
      correspondence to the observed spleen enlargement. We concluded that a
      theobromine-enriched diet affects progeny development in both prenatal and
      postnatal periods. Consequently, particular attention should be paid to the
      reduction of theobromine consumption, and most probably that of other
      methyloxanthines, during pregnancy and lactation.

PMID- 15573694
TI  - Determination of telomere length by flow-fluorescence in situ hybridization in
      Down's syndrome patients.
AB  - A new method for measuring telomere length in a population of Down's syndrome
      patients aged 18-60 years old is presented. The method is based on flow cytometry
      and quantitative fluorescence in situ hybridization (flow-FISH) on whole cells.
      At least three methods for measuring the length of telomere repeats have been
      described: (i) Southern blot analysis, and quantitative FISH using either (ii)
      digital fluorescence microscopy (Q-FISH) or (iii) flow cytometry (flow-FISH).
      Both Southern blot analysis and Q-FISH have specific limitations and are time
      consuming, whereas flow-FISH needed relatively few cells (1.5-2.5 x 106) and
      could be completed in 24-48 h. The method can be used to rapidly determine
      telomere length in subsets of nucleated blood cells from patients with age
      related diseases such as Down's syndrome, Alzheimer's disease and Werner
      syndrome.

PMID- 15573695
TI  - [Ontogenetic features of psychophysiological mechanisms of perception of speech
      emotional component in musically gifted children].
AB  - Cerebral mechanisms of musical abilities were explored in musically gifted
      children. For this purpose, psychophysiological characteristics of perception of
      emotional speech information were experimentally studied in samples of gifted and
      ordinary children. Forty six schoolchildren and forty eight musicians of three
      age groups (7-10, 11-13 and 14-17 years old) participated in the study. In
      experimental session, a test sentence was presented to a subject through
      headphones with two emotional intonations (joy and anger) and without emotional
      expression. A subject had to recognize the type of emotion. His/her answers were
      recorded. The analysis of variance revealed age- and gender-related features of
      emotional recognition: boys musicians led the schoolchildren of the same age by 4
      6 years in the development of mechanisms of emotional recognition, whereas girls
      musicians were 1-3 years ahead. Musical education in girls induced the shift of
      predominant activities for emotional perception in the left hemisphere; in boys,
      on the contrary, initial distinct dominance of the left hemisphere was not
      retained in the process of further education.

PMID- 15573696
TI  - [Gender differences in EEG coherence during memorization of dichotically and
      monaurally presented verbal stimuli].
AB  - Gender differences in changes of coherence values in the theta and alpha
      frequency bands during encoding of dichotically and monaurally presented verbal
      information were studied. Right-handed students (14 male and 14 female subjects)
      participated in experiments. The EEG was recorded from 16 electrodes placed at
      homologous sites of the left and the right hemispheres. In male subjects,
      numerous differences in coherence values between conditions of dichotical and
      monaural word presentation were found in the theta2- and alpha1-bands, in
      females, the differences were most pronounced in the theta1- and theta2-frequency
      bands. Numerous differences in coherence values differentiated between dichotic
      and left-sided monaural presentations in males and between dichotic and right
      sided monaural presentations in females. As compared to dichotic presentation, in
      condition of the monaural presentation, higher coherence values were observed in
      men and lower in women. The features of gender differences in frequency-spatial
      patterns of changes in EEG coherence values under conditions of bilaterally and
      unilaterally directed attention in male and female groups may testify that female
      subjects predominantly use right-hemispheric processing strategy, whereas male
      subjects use, mainly, left-hemispheric strategy for selection and memorization of
      concrete nouns.

PMID- 15573697
TI  - [Cortical positive potentials in the period of eye fixation prior to saccades and
      antisaccades].
AB  - The EEG of 10 right-handed healthy subjects preceding saccade and antisaccade
      with mean values of latency in the eye fixations period were selected and
      averaged. The positive potential P2 appearing on the fixation stimuly switching
      on and slow positive wave following after it were more prominent before
      antisaccades than normal saccades. Space-temporal analyses of presaccadic
      potentials showed that right frontal cortex was activated more before
      antisaccades. These findings suggest that right cortical hemisphere dominate in
      spatial attention and inhibition of automatic saccades to visual stimuli in the
      period of antisaccades preparing. During the period of central fixations
      "intermediate" positivity potentials, developing in 600-400 ms prior to saccade
      or antisaccade onset, were find out. These potentials were predominantly recorded
      in the left frontal and frontosagittal cortical areas. The obtained evidence
      suggest that "intermediate" positive potentials a period related to the process
      of motor attention, anticipation and decision making in the period of eyes
      fixation.

PMID- 15573698
TI  - [Psychophysiologic parameters of reproducing emotions in healthy subjects and
      patients during the first episode of depression].
AB  - We analyzed the spectral power of EEG rhythms and some psychological features in
      patients with depression (first episode) and in healthy subjects. In the control
      group, the distributions of the spectral power of the alpha3 and gamma rhythms
      was symmetrical. In reproducing joy, the power of the alpha3 rhythm increased in
      the occipital and that of the gamma rhythm increased in the temporal areas of the
      left hemisphere. In depressive patients, predominant activation of the left
      posterior cortical quadrant in the alpha3 band was observed both in the baseline
      activity and during reproducing emotions of both valences. In these patients, the
      gamma rhythm predominated in the anterior regions of the right hemisphere during
      rest. The mental reproduction of joy and grief in depressive patients shifted the
      maximal gamma rhythm spectral power to the occipital cortical regions. Thus, in
      depressive patients, any emotional load, regardless of its valence, results in a
      decrease in the pathologic gamma activity and makes the distribution of cortical
      electric activity more close to that of healthy subjects.

PMID- 15573699
TI  - [Comparative characteristics of psychoemotional patterns in Albino and Wistar
      rats].
AB  - Analysis of psychoemotional behavioral component in Albino and Wistar rats during
      solving a cognitive task showed that intra-population differences were determined
      by the relationship between passive and active forms of unconditioned reactions.
      Quick-learning rats from both populations were characterized by the dominance of
      active forms of psychoemotional reactions over the course of training. The
      learning process in slow-learning rats was accompanied mainly by passive
      emotional manifestations, whereas active reactions dominated at the stage of
      habit realization. Passive forms of manifestations prevailed over active forms
      over the course of training in both Albino and Wistar rats which failed to solve
      the task. The interpopulational psychoemotional differences were quantitative and
      depended only on the learning styles. Wistar strain was characterized by a
      decreased percent of animals which were able to solve a cognitive task (40%
      versus 80% in Albino rats), affective flatness and decreased tolerance to
      information loadings.

PMID- 15573700
TI  - [Structure and electrophysiological properties of bursting neurosecretory cells
      in a peripheral sensory ganglion of the pond snail Lymnaea stagnalis].
AB  - A group of peripheral neurosecretory oscillating neurons belonging to the type of
      parabolic bursters, were identified in the osphradium (peripheral putative
      chemosensory organ) of the pond snail Lymnaea stagnalis. The cells are unipolar,
      their process ramifies and terminates in the nerve. Applications of 5-HT caused
      long-lasting bursts with significantly increasing duration and frequency of
      spikes. GABA and FMRFamide inhibited the activity of these cells.

PMID- 15573701
TI  - [Audiogenic kindling in WAG/Rij rats: change in behavioral and
      electrophysiological responses to repetitive short acoustic stimulation].
AB  - Running and tonic convulsions induced by sound stimulation (audiogenic seizures,
      AS) are known to be brainstem-dependent, but their repeated induction leads to
      the recruiting forebrain structures into AS expression manifested by the
      development of clonic convulsions and cortical epileptic activity (audiogenic
      kindling). Behavioral and electrophysiological manifestations of audiogenic
      kindling were studied in AS-prone WAG/Rij rats exhibiting two types of
      genetically determined generalized seizures: convulsive audiogenic and
      nonconvulsive absence (spontaneous spike-wave discharges generated by
      thalamocortical circuits). Twenty three repeated (with 2 days intervals) sound
      stimulations inducing a short running episode led to a progressive increase in AS
      duration from 6.2 +/- 0.4 s to 24.7 +/- 2.9 s mainly due to the appearance of
      additional postrunning facial-forelimb clonic convulsions of increasing duration
      and severity. Fully kindled (Racine's stage 5) seizures were accompanied by a
      bilateral slow-potential wave of cortical spreading depression (SD)
      nonsynaptically propagating to both striata and by a long-term postictal
      suppression of spontaneous absence seizures. Neither corticostriatal SD, nor the
      spike-wave discharges suppression were observed after running induced by sound in
      non-kindled rats or by attenuated (subthreshold for clonus) sound in kindled
      rats. Subthreshold stimulation of kindled rats provoked postictal high-amplitude
      spiking in the cortex. It is concluded that the recruitment of the cortex into a
      kindled AS network triggers a corticostriatal SD which may underlie the postictal
      inhibition of non-convulsive seizures, which follow the kindled AS.

PMID- 15573702
TI  - [Study of giant depolarizing activity in the neonatal hippocampal neurones].
AB  - Spontaneous oscillatory activity is a general feature of developing neural
      networks. Early in postnatal development, spontaneous network-driven events,
      termed giant depolarizing potentials (GDPs), occur synchronously over the entire
      hippocampus. By performing simulation of hippocampal network with using
      physiology parameters of the neurons and its network from the present experiments
      and literature dates, we investigated the participation of the different
      components of network in the generation of GDPs. Comparing the results of the
      model and in vitro experiments we conclude that are necessary for the GDP
      generation involvement the activation of GABAergic, glutamatergic inputs and
      perhaps gap junction.

PMID- 15573703
TI  - [Regulation of the length of the snail tentacle by the concentration-dependent
      contraction].
AB  - The tentacle of terrestrial snail with olfactory organs on the tips display
      complex behavior when snail investigates the new environment. We reconstructed
      the trajectory of the tentacle in three dimensions from two simultaneous video
      recordings in freely moving snail without odor and after odor application. We
      found that without oder the snail displayed continuous environment scanning with
      elongated tentacles. Odor application elicited startle-like short-term flexions
      of the tentacle which were independent from odor concentration and concentration
      dependent gradual tentacle contraction. Identified central motoneuron MtC3 is
      known to produce the most part of the central tentacle retraction to the noxious
      stimuli. In nose-brain preparation the MtC3 responded to odors in concentration
      dependent manner similar by dynamics and duration to the concentration-dependent
      gradual tentacle contraction in intact snail. It suggests that the MtC3 provides
      the central control of the extent of the scanning area by limiting the tentacle
      length. The MtC3-related gradual contraction of the tentacle can be aimed to tune
      the olfactory behavior of the terrestrial snail to the particular odor
      environment.

PMID- 15573704
TI  - [Postnatal development of conditioned reflex behavior: comparison of the periods
      related to the onset of the different forms of hippocampal plasticity in rats].
AB  - Fear conditioning, escape and active avoidance reactions in two-way avoidance
      paradigm were compared in rats of different ages. Fear conditioning, but not
      escape and active avoidance reactions could be acquired on the 16-17th postnatal
      days, and the acquisition was more effective than in adults. Escape behavior
      matured beginning from the 18th postnatal day reaching the adult level within the
      3d-4th postnatal weeks. Maturation of the mechanisms of Pavlovian (fear reaction)
      and instrumental (escape reaction) conditioning did not facilitate the
      acquisition of two-way avoidance until the 4th postnatal week, young animals
      displayed low acquisition in this period. The maturation of these memory
      processes is proposed to be related to developmental stages of different
      mechanisms of hippocampal plasticity.

PMID- 15573705
TI  - [Electrographical correlates of adequate and erroneous responses caused by
      conditioned signals of different functional sign during instrumental conditioning
      in dogs].
AB  - Power spectral (in the broad frequency band of 1-225 Hz) of short-term (less than
      1 s) EEG reactions were studied in dogs in the course of instrumental food
      conditioning. These reactions appeared in different cortical areas in response to
      differentiating signals under conditions of both adequate and erroneous
      responses. The EEG power of such reactions was several times lower as compared to
      responses to positive signals, mainly, at the expense of the frequencies in the
      band of 90-225 Hz (the power of which was higher than that of the traditional
      band of 1-30 Hz and the gamma band of 30-80 Hz). The frequency composition of EEG
      reactions accompanying adequate responses was defined, mainly, by discrete
      subgroups of high-frequency components. During erroneous responses, the discrete
      structure of the corresponding EEG reactions was broken.

PMID- 15573706
TI  - ["The avoidance" of the direct current application to the sensorimotor cortex (a
      computer-controlled experiment in rabbits)].
AB  - In a computer controlled experiment the electric activity of rabbits right
      sensorimotor cortex was recorded in the area of the excitation focus produced by
      the direct current (2 mcA) application. The current was switched on at the 5th,
      10th and 15th minutes of experiment only in cases when the mean amplitude of the
      delta waves exceeded the baseline. The current was switched off at the mean
      amplitude of the delta waves exceeding the baseline level by 50%. After training
      some experiments (2-4), rabbits learned to change their functional state in such
      way that they "avoided" the action of the direct current.

PMID- 15573707
TI  - [Influence of the medial raphe nucleus damage on discharge activity of the
      central and bazolateral nuclei of the amygdala].
AB  - It has been revealed pronounced differences between neuronal discharge activity
      of central and basolateral nuclei of amygdala. After midbrain raphe medial
      nucleus damage discharge activity of amygdalar nuclei markedly changes, mainly by
      reciprocal manner. It is suggest that serotonergic afferentations from nucleus
      raphe to show various influence upon discharge activity of central and lateral
      nuclei of amygdala.

PMID- 15573708
TI  - [Effects of central administration of beta-amyloid peptide (25-35):
      pathomorphological changes in the hippocampus and impairments of spatial memory].
AB  - A possible relationship between the amnesia induced by central administration of
      beta-amyloid (25-35) [Abeta(25-35)] and neurodegeneration in the hippocampus was
      studied. Male Wistar rats received a single intracerebroventricular injection of
      Abeta(25-35) at a dose of 15 nmol. One month after the administration, animals
      were trained in an eight-arm radial maze. After the training, a histopathological
      investigation of the hippocampus was carried out using brain slices stained with
      hematoxylin/eosin. Abeta(25-35) induced impairments in reference and working
      memory in the eight-arm radial maze. A moderate decrease in neuronal cell number
      was demonstrated in the CA1, but not in the CA3 subfield of the hippocampus. The
      number of both reference and working errors negatively correlated with the number
      of neurons in hippocampal CA1. The results are the first evidence for a specific
      relationship between neurodegeneration in the CA1 subfield of rat hippocampus and
      impairments of learning and memory induced by Abeta(25-35).

PMID- 15573709
TI  - [Selection of behavioral test parameters for estimation of typological features
      of rat behavior].
AB  - Behavior of 86 rats was examined in three behavioral tests, i.e., open field,
      forced swimming and emotionality by F. King. The results of statistical analysis
      of all the indices obtained with application of factor analysis suggest that the
      three tests characterize four relatively independent behavioral components:
      emotionality, locomotor-exploratory activity, olfactory performance, and
      resistance to adverse emotional factors. A contribution of each measured
      parameter to the above components was estimated. Such an approach makes it
      possible to reasonably select most important behavioral features when estimating
      locomotor activity and emotionality of animals.

PMID- 15573710
TI  - Pharmaceutical gifts of medicine.

PMID- 15573711
TI  - Successful public/private donation programs: a review of the Diflucan Partnership
      Program in South Africa.
AB  - A review of the partnership between Pfizer Inc. and the South African Ministry of
      Health to distribute free Diflucan (fluconazole) in the Diflucan Partnership
      Program (DPP) demonstrates that product donations may be a useful response to
      AIDS if they are coupled with efforts to build means of drug distribution and
      enhance professional healthcare capacity to treat patients. Equally important is
      the creation of a new set of productive working relationships between
      stakeholders who came to the project with different backgrounds and perspectives,
      as well as a frankly disparate set of objectives. A decision tree illustrates how
      these relationships were built into the DPP. This review concludes with a few
      lessons learned in providing medicines not only to South Africa, but also to the
      77 other African countries now participating in the DPP. As the search for new
      treatments and vaccines continues, increasing access to existing medicines
      through targeted donations--including training and infrastructure support--is the
      most practical way for the health community to address the problem of ill health
      among the poor. In addition to a detailed analysis of the DPP, there is also a
      discussion of the benefits of a donation program that addresses the AIDS crises
      on a global scale. This review may serve as a blueprint for establishing programs
      that are successful in fighting AIDS and improving the lives of millions of
      people.

PMID- 15573712
TI  - Fragility fractures in HIV-infected patients: need for better understanding of
      diagnosis and management.
AB  - HIV infection, AIDS, and antiretroviral therapy (ART) have been associated with
      bone fragility fractures, although the prevalence and incidence are not well
      studied by researchers. In HIV and ART, osteopenia and osteoporosis are
      multifactorial, and health promotion or medical health maintenance should
      anticipate and prevent morbidity of bone fragility fractures.

PMID- 15573713
TI  - Atazanavir--a once-daily HIV protease inhibitor that does not cause dyslipidemia
      in newly treated patients: results from two randomized clinical trials.
AB  - Protease inhibitor (PI) treatment can result in dyslipidemia in a significant
      proportion of patients. Atazanavir (ATV) is a once-daily PI that has not been
      associated with clinically relevant increases in total cholesterol (TC), fasting
      low-density lipoprotein cholesterol (LDL-C), or fasting triglyceride (TG)
      concentrations. The objectives of this paper were to evaluate lipid profiles in
      untreated patients, and investigate the frequency and severity of dyslipidemia in
      the same individuals after treatment with ATV or nelfinavir (NFV) for 48 weeks.
      Two multinational, randomized, active-controlled, blinded trials compared the
      safety and efficacy of ATV and NFV in combination with two nucleoside reverse
      transcriptase inhibitors (NRTIs) in antiretroviral (ARV)-naive patients. Serum
      lipid concentrations were analyzed in patients who had available measurements
      both at baseline and at week 48. Patients who had missing data at either time
      point were not included. Lipid levels remained within baseline ranges at week 48
      with ATV treatment, whereas clinically relevant elevations in TC, fasting LDL-C,
      and fasting TG concentrations occurred with NFV treatment. Mean changes from pre
      treatment baseline in fasting LDL-C ranged from -6 percent to +6 percent in the
      ATV-treatment groups, and from +27 percent to +31 percent in the NFV-treatment
      groups. After 48 weeks, there was a substantive increase in the proportion of NFV
      treated patients who would be recommended for lipid-lowering treatment by
      National Cholesterol Education Program (NCEP) guidelines, whereas a lesser
      proportion of ATV-treated patients would be recommended for lipid-lowering
      treatment. Atazanavir does not lead to dyslipidemia in ARV-naive patients, and
      may limit the need for lipid-lowering strategies to reduce the risk of
      cardiovascular disease.

PMID- 15573714
TI  - [Maintenance of the hypnotic component of general anesthesia with feed-back
      regulation].
AB  - The purpose of the study was to design and investigate the closed-loop propofol
      system (CLPS) with a mean arterial pressure (MAP) controller in open-heart
      surgery. CLPS consists of a 386 PC, a blood pressure sensor and an infusion pump.
      The C language computer program sets the propofol infusion rate based on an
      empirical algorithm including proportional component to maintain the measured MAP
      more closely to the target MAP (85% of patient standard MAP). The propofol
      concentrations were calculated by the pharmacokinetic/pharmacodynamic model
      differential equations solving every 30s. CLPS was used in 214 NYHA II-IV
      patients, aged 16-74, undergoing various open-heart procedures. The mean target
      MAP was 75.2 +/- 4.5 mm Hg. The measured and target MAP difference did not exceed
      22% perioperatively. The bispectral index varied from 42.7 +/- 1.2 (tracheal
      intubation) to 41.8 +/- 0.1 (skin suture) with a variation of the propofol site
      effect concentration ranging from 2.9 +/- 0.09 to 1.8 +/- 0.1 microg/ml. It was a
      closed negative correlation (r = 0.84; p < 0.01) between the propofol site effect
      and the MAP during the initial period of anesthesia. There were not any
      significant changes in the blood cortisole level during the procedures. The
      recovery time was 1.4 +/- 1.5 min after propofol infusion; 95.5% of patients were
      extubated in the operating room.

PMID- 15573715
TI  - [Effect of intravenous hypnotics on autonomic response in patients with ischemic
      heart disease].
AB  - The purpose of the case study was to investigate the effect from the bolus dosing
      of midazolam and ketamine on the autonomic hemostasis in patients with ischemic
      heart disease (IHD) with the prevalence of the activity of sympathetic or
      parasympathetic parts in the autonomic nervous system. The IHD patients (n = 75)
      were examined, after scheduled preoperative therapy, active orthostatic tests and
      tests of cardiac rate variability (CRV to determinine a type of autonomic
      response. After orthostatic-test results were analyzed, patients with
      sympathicotonic (n = 15) and vagotonic (n = 15) types of vegetative response were
      selected. After midazolam at 0.08-0.12 mg/kg and ketamine at 0.5-1.3 mg/kg were
      administered, CRV was analyzed in the operating theater.

PMID- 15573716
TI  - [Use of "NovoSeven" (rFVIIa) hemostatic in patients operated with extracorporeal
      blood circulation].
AB  - The "NovoSeven" drug was used in 25 patients (male - 18, female - 7) operated on
      the heart and main vessels including with artificial extracorporeal circulation
      (AEC). Patients did not have any clinically significant impairment in blood
      circulation before surgery. Perioperatively, all of them and, immediately after
      surgery, 4 them had uncontrollable hemorrhages at 10-25 ml/min in spite of
      extensive hemostatic therapy, including freshly frozen plasma, cryoprecipitate,
      thromboconcentrate, trasilol and ?-amine acid. Yet in 30 min after "NovoSeven"
      administration, hemorrhages seized virtually in all patients irrespective of a
      surgical intervention. It normalized the hemostasis by it differential action on
      an impairment depending on an activated or suppressed coagulation. Thus, the
      conclusion is that the "NovoSeven" (rFVIIa) is an effective hemostatic ensuring
      the correction of massive intra- and postoperative blood losses in cardiosurgery
      patients. The drug cuts the need in using the donor-blood components, thus,
      diminishing the risk of multi organ failure that can develop immediately after
      surgery.

PMID- 15573717
TI  - [Using non-invasive mask lung ventilation in cardiosurgical patients with acute
      respiratory distress syndrome].
AB  - Twenty patients aged 33 to 71 (54 +/- 6) years (male - 13, female - 7) operated
      on the heart and main vessels were included in the case study. I.e. those patient
      were investigated, whose immediate postoperative results were complicated by the
      syndrome of multiple organ failure (SMOF) that developed due to different
      etiology shock, huge blood loss and hemotransfusion or to the syndrome of acute
      postperfusion lung damage. NIMLV was made at the resolution stage of SMOF and
      ARDS after artificial pulmonary ventilation (APL) for as long as 5-7 days. The
      indications for extubation of patients were as follows: PaO2/FiO2 of 200 and more
      mm Hg, respiratory rate (RR) of less than 30 per min, respiratory volume of more
      than 6 ml/kg with pressure support at inspiration of less than 5 cm H2O and with
      the total pressure at the exhalation end of no more than 3 cm H2O. Mask
      ventilation sessions were started in a growing dyspnea of more than 26 per min, a
      decreased content of oxyhemoglobin in arterial blood (below 95% at oxygen
      inhalation of 10-15 l/min), involvement of auxiliary muscles in breathing and at
      subjective complaints of patients related with complicated breathing and with
      being short of air. The mask SIMV ventilation with a preset apparatus-aided rate
      of inhales of 2-6/min, with Bi-PAP and PSV inhale pressure of 15 cm/ H2O and with
      PEEP of 3-5 cm/ H2O was made by 40-120 min sessions; the number of IFMLV sessions
      ranged from 6 to 22/patient, mean - 11 +/- 1.1 h. The total IFMLV duration was
      10.7 +/- 1.1 h. The need for respiratory support persisted for 4-6 days after
      extubation. In 18 (90%) of 20 patients, the mask pulmonary ventilation resolved
      the respiratory insufficiency. Two (10%) patients were reintubated because of
      progressing multiorgan failure and because of obturation of the left main
      bronchus. A questioning of patients on the comfort degree of mask ventilation
      denoted the Flow-by triggering to be by far better tolerated by patients versus
      the pressure triggering.

PMID- 15573718
TI  - [Reducing the need in donor blood in reconstructive surgery of the aorta: using a
      Cell Saver apparatus].
AB  - The possibility of using a Cell Saver "Sequestra 1000" apparatus (Medtronics) for
      reducing the need for donor blood in reconstructive surgery for aortic aneurism
      was evaluated within the case study. Thirty-seven patients, who were made
      different reconstructive procedures on the ascending and abdominal aorta, were
      examined. Twelve patients with aneurism in the ascending aorta section (AAS) and
      with insufficiency of the aortal valve were made prosthesis of AAS and aortal
      valve under extracorporeal circulation (AEC). Twenty-five patients, who were
      operated on the abdominal aorta section, were resected aneurysm with linear
      prosthesis (9), aorto-hip bifurcational alloprosthesis (15) and branching of
      arterio-venous fistula (1). Five patients with aneurysm in the abdominal aorta,
      including 3 cases of aneurysm rupture, were operated on the emergency basis. The
      use of a Sequestra 1000 (Medtronics) apparatus based on the Cell Saver technology
      aorta reconstructions cut essentially the need in donor packed red blood cells at
      the intraoperative (3.6 times) and postoperative (2.8 times) stages.

PMID- 15573719
TI  - [The state of hemostasis in patients after mini-invasive aorta and coronary
      artery bypass surgery].
AB  - The paper represents data on the condition of the hemostasis of plasma and
      platelet chains as well as of the system of natural anticoagulants and
      fibrinolysis as observed in cardiosurgical patients after mini-invasion coronary
      artery bypass surgery. An intensified generation of platelets, postoperative
      hyperaggregation of platelets and a lower level of natural anticoagulants in
      blood were shown as to be compensated for by an activated system of fibrinolysis.

PMID- 15573720
TI  - [Prevention and treatment of postoperative nausea and vomiting (results of a
      multicenter study)].
AB  - Described in the paper are the results of a multicenter study that was conducted
      at 11 health-care facilities of the Russian Federation and that was based on an
      analysis of 623 medical records of adult patients operated on with general
      anesthesia of different variations. There were 154 (24.7%) males and 469 (75.3%)
      females, aged 16 to 90. The study denoted the need in and possibility of
      preventing and arresting the PONV; it also outlined those forms of ondansetron
      (Zofran) that can be used for the purpose, they are: parenteral and lingual pills
      and rectal suppositories. An assumption was put forward on the significance of
      PONV conductive factors and on the most effective forms of ondansetron from among
      the mentioned above. An understanding, resulting from the study, on that PONV is
      of the multietiology nature and on that its probability increases in proportion
      to a compatibility of provoking factors, like sex, surgery technique as well as
      duration of anesthesia and its variation is of importance. The efficiency of
      medicamental prevention of PONV by a blocker of HT3-receptors, i.e. by
      ondansetron (Zofran), is to a great extent predetermined by that if the form and,
      probably, dose of the drug is in line with a combination of the above factors,
      which needs further research.

PMID- 15573721
TI  - [Anesthesiological problems in the surgical treatment of chronic obstructive
      pulmonary disease].
AB  - Maintenance of effective gas exchange made with respect to surgical comfort and
      lower risk of intraoperative lung damage is the main problem in the anesthetic
      management of surgical reduction of pulmonary volume (SRPV). Described in the
      paper is the experience of anesthetic management made in 10 patients in SPRV. The
      method of differential ALV (DALV) with continuous positive pressure in airways
      (CPPA) made for the ventilation support of the independent lung was found to be
      the only effective technique ensuring an adequate gas exchange in surgery for
      SPRV in patients with diffusive pulmonary emphysema (DPE). It accounts for the
      pathophysiological specificity of diffusive pulmonary lesion. At the same time,
      it provides for an optimal surgical comfort and for the most cautious
      manipulations on the lung. Such a combination improves the overall surgical
      results. The high-frequency respiratory support to the operated lung is
      contraindicated in such patients because of hyperinflation of the affected lung.

PMID- 15573722
TI  - [Spinal operations performed in prone position: pulmonary gas exchange,
      hemodynamics, and possible complications].
AB  - Invasive and non-invasive studies have been used to study the cardiac and
      respiratory systems in 93 patients during prolonged prone surgical interventions
      into the vertebral column. Pronounced hemodynamic changes have been found to be
      absent at the stage of anesthetic anesthesia and while turning the patient with
      to the prone position. Gas exchange is determined by the increase in alveolar
      dead space, PaCO2, and PaO2. The position complications during these
      interventions are caused by errors while placing the patient on an operating
      table.

PMID- 15573723
TI  - [Hemodynamic changes during anesthesia in orthotopic liver transplantation in 1-5
      year-old children].
AB  - The anesthetic management of orthotopic hepatic transplantation (OHT) was
      analyzed in 49 children aged 1 to 15 years. Ten protocols of anesthesia
      implemented in small-age children (1 to 5 years) were analyzed in detail. The
      mean age of children (6 girls, 4 boys), operated on in 2002-2004, was 3.0 +/- 2.7
      years; their mean weight was 13.6 +/- 4.17 (9-22) kg. The purpose of the case
      study was to study the dynamics of the cardiovascular system and the pattern of
      hemodynamic impairments accompanying the anesthetic course in OHT from a living
      related donor. All surgeries were made under balanced general anesthesia:
      induction - midazol (0.04 +/- 0.01 mg/kg), cetamine (2.77 +/- 0.64 mg/kg),
      phentanile (3.1 +/- 0.21 mg/kg), myorelaxation--pipecuronium bromide (arduan)
      (80.3 +/- 11.44 microg/kg). Low-flow inhalation by isofluoran -0.8-2.0 ALC%,
      minimal-flow (0.7-1.6 MAC), was used.

PMID- 15573724
TI  - [Optimization of anesthetic management in blepharoplasty].
AB  - The anesthetic management in cosmetic surgery must be as much controllable, safe
      and comfortable for a patient as possible, i.e. it must be in line with all
      requirements of outpatient surgery. Fifty-two patients were added, to the
      anesthetic-management scheme in blepharoplasty, the following: ketoralak - 0.4
      0.6 mg/kg, transamine - 13.5-15 mg/kg, analgetics with non-opiate effect and
      antiemetic tropisetron - 0.05-0.08 mg/kg. It ensured an adequate analgesic action
      without suppression of the breathing function and a more comfortable
      postoperative course with a lesser postoperative syndrome of nausea and vomiting 
      by 3-4 times less versus the controls.

PMID- 15573725
TI  - [Safety and quality of myoplegia in different types of abdominal surgeries].
AB  - The efficiency of new non-depolarized myorelaxants, i.e. of rocuronium and
      cisatracurium, in abdominal surgery with general anesthesia (combined or total
      intravenous anesthesia) of 114 patients was evaluated clinically and
      accelerometrically. The use of the above drugs at 2 x ED95 was confirmed to
      ensure a high-quality myorelaxation in different surgery variations (laparoscopy
      or laparotomy). A lack of effect on the hemodynamics (according to continuous non
      invasive monitoring) and release of histamine (according to radioimmunology
      assay) make it possible to use the myorelaxants in patients with concurrent
      cardiovascular disease and with burdened allergic history. A bigger degree of
      prognosticated effect duration is typical of cisatracurium versus rocuronium,
      whereas the latter is a myorelaxant of choice in case a fast trachea intubation
      is needed.

PMID- 15573726
TI  - [New russian myorelaxant vero-pipecuronium (pipecuronium bromide) used for the
      anesthetic management of operations on the thorax and abdomen organs].
AB  - The experience of clinical use of the new Russian myorelaxant of the non
      depolarizing action vero-pipecuronium (pipecuronium bromided) manufactured by
      "Veropharm" is described. Vero-pipecuronium was found to ensure splendid and good
      conditions for the intubation of the trachea and to maintain reliably
      myorelaxation. The recommended doses and availability of an antidote (prozerine)
      provide for a sufficiently controllable myorelaxation. Vero-pipecuronium does not
      virtually exert any effect on the parameters of hemodynamics and can be
      successfully used in patients with a high anesthetic risk including heart
      surgeries. Thus, Russian vero-pipecuronium has now an effective and safe
      myorelaxant manufactured inside the country, whose parameters are not inferior to
      those of pipecuronium bromide (arduan) manufactured by "Gedeon Richter", Hungary.
      Since the described drug is made in Russia, one can hope it will be highly
      effective both economically and pharmacologically.

PMID- 15573727
TI  - [Pharmacoeconomic assessment of prevention of the postoperative nausea and
      vomiting syndrome in plastic (esthetic and reconstructive) surgery].
AB  - A comparative "cost-efficiency" pharmacoeconomic analysis was made for 5
      different anti-emitting drugs, i.e. for "Navoban", "Zofran" (intravenous
      administration, 8 mg; and suppositories, 16 mg) and for "Metipred"
      (methylprednisolone) used in aesthetic and reconstructive surgeries of 86
      patients. All the drugs were found to be effective for the prevention of PONV.
      Clinically, the efficiency decreased in the following order: "Novoban" and
      "Zofran" suppositories 16 mg, "Metiored" and "Zofran" intravenous administration
      8 mg. As for "cost-efficiency", preference should be given to "Metipred".

PMID- 15573728
TI  - [Clinical-and-pathophysiological prerequisites of impaired breathing and ensuring
      of safety in drug-induced depression of consciousness].
AB  - Seventy-three patients operated on under anesthesia based on regional blocks were
      examined. Thiopental-sodium (T; n = 29), myadozalam (M; n = 10) and propofol (P;
      n = 24) were used for sedation. The conditions of breathing and of gas exchange
      were evaluated by the findings of pneumotachography: V(peak insp), P(peak insp),
      P(100) Raw, breathing pattern, SpO2, PEtCO2 and EMG from mouth-diagram muscles.
      The obtained results were made use of to draw up a rating scale for impaired
      breathing, which is based on the respiratory volume and respiration rate of gas
      exchange as well as on different variations of respiratory support. Irrespective
      of a sedation type and of a degree of consciousness suppression, the impaired
      breathing was registered in 90-100% of cases: obstruction of the respiratory
      tracts was predominant in T (higher Raw); in M--depression of the respiratory
      center (lower P(100); in P--a pronouncedly lower of EMG, and, respectively, a
      weakened contraction of diaphragm (lower P(peak insp)). Depression of the
      respiratory center was found to occur irrespectively of a drug used in sedation,
      however, the mechanisms of obstruction were different: in T--impaired breathing;
      in M--impaired phase muscle activity. Sedation by P was not accompanied by any
      clinically valuable obstructive signs.

PMID- 15573730
TI  - [A new method of monitoring the psycho-emotional condition in patients during
      balanced anesthesia based on regional blockades].
AB  - The potentialities of a skin-galvanic reaction (SGR) were studied, to evaluate
      the psycho-emotional status, in 9 sedated (midazole, thiopental-sodium, propofol)
      classes I and II ASA patients operated (10 interventions) under regional block.
      An original software was designed to analyze the SGR; it detects the signs of
      psycho-emotional discomfort (including positional discomfort) in drug-induced
      depression of consciousness as well as the uncontrollable moments of falling
      asleep and awakening.

PMID- 15573729
TI  - [Subarachnoid anesthesia in patients with high surgical risk].
AB  - The hemodynamics was intraoperatively studied in 43 patients with multicentric
      atherosclerosis, ASA III-IV, operated on the peripheral vessels of legs with
      balanced anesthesia based on subarachnoid block. It was established in regional
      sympathetic block and in the course of the whole surgery that the parameter of AP
      were decreased by 20-25%, those of heart rate--by 15% and of TPVR--50%, whereas,
      the parameters of cardiac performance were stable. The authors discuss the
      specificity of hemodynamic restructuring under subarachnoid block in patients
      with at surgical risk due to vascular pathology.

PMID- 15573731
TI  - [Pain: clinical picture and objective criteria of therapy adequacy].
AB  - The paper is dedicated to electroencephalographic monitoring in the therapy and
      rehabilitation of patients with acute radicular pain syndromes of the disc
      etiology. Spontaneous electromyograms (EMG) of the shin muscles in healthy and
      affected legs and stimulation electroneurograms were registered in 52 patients;
      the readings were subsequently processed on the basis of Fourier analysis for the
      4-sec maximal muscle contraction. The studies made it possible to detect the
      degree of destructive changes in the neuromotor apparatus and to monitor its
      functional recovery in pharmacotherapy, central and peripheral blocks, artificial
      correction of movements and in acupuncture.

PMID- 15573732
TI  - [Hemodynamic parameters and saturation of the cerebral cortex blood with oxygen
      during extracorporeal circulation in heart surgery].
AB  - Sixty-three patients were intraoperatively examined during heart surgery with
      extracorporeal circulation (AEC). They were operated on for an affected heart
      valve apparatus (AHVA) and ischemic heart disease (IHD). There was a
      perioperative monitoring of central hemodynamics, pressure in the bulb of
      superior jugular vein (BSJV) and electroencephalography (EEG). Regional
      oxygenation of the brain was made in real time by a INVOS3100 oximeter
      (SOMANETICS, USA). A maximal saturation of the cortex blood with oxygen at AEC
      was registered in patients with AHVA at an average pressure below 70 mm Hg, and
      in patients with IHD--at 85 mm Hg. An increased pressure in BSJV at a constant
      mean arterial pressure and at AEC is related with blood outflow from the venous
      collector of the brain.

PMID- 15573733
TI  - [Cerebral oximetry in the perioperative evaluation of the reserve of cerebral
      circulation in patients with brachiocephalic artery lesions].
AB  - The reactivity of cerebral vessels and the reserve of collateral compensation of
      cerebral flow were studied in 71 patients with perioperative carotid stenosis of
      different degrees. Cerebral oximetry was made at rest and during hypercapnic and
      compression loads. The method's efficiency was demonstrated for the preoperative
      evaluation of the cerebrovascular reserve in patients with atherosclerotic
      affection of vessels in the brachiocephalic stem. A comparison of the
      preoperative and intraoperative dynamics of rSO2 at compression points at the
      feasibility of using the cerebral oximetry in predicting the degree of reduced
      regional oxygenation of the brain in the basin of an intraoperatively pinched
      artery.

PMID- 15573734
TI  - [Immunocorrectors in the complex treatment of postoperative suppurative
      inflammatory complications in surgical patients and monitoring of immunological
      parameters].
AB  - The results of monitoring of immune parameters in different categories of
      surgical patients with postoperative purulent-inflammatory complications are
      described in the paper. The combined type of secondary immunodeficiency and
      degree second immunodeficiency according to A.M. Zemskov were detected in all
      patients. Immunocorrecting drugs, like polyoxidonium, imunofan and likopid, were
      added to the complex treatment of patients with the above complications. Their
      administration normalized the dynamic clinical course of the purulent
      inflammatory processes and restored the immunological parameters.

PMID- 15573735
TI  - [The immune status and its correction in patients after reconstructive surgeries
      for cicatricial stenosis of trachea].
AB  - The immune status was analyzed in 28 patients with cicatricial stenosis of the
      trachea for the purpose of determining the type and nature of affection as well
      as for the purpose of evaluating the clinical efficiency of galavit
      immunomodulator. Combined impairments were diagnosed in the patients. Moderately
      decreased CD4+, CD8+, CD16+, significantly decreased CD25+, HLA-DR, CD71+ and
      increased CD4+/CD8+ were detected at the cell level. An essentially lower CD20+,
      a higher content of IgG and a reduced FAN were observed in the humoral chain.
      Therefore, galavit, when used preoperative and immediately after surgery in
      patients with cicatricial stenosis of the trachea, had a positive effect on the
      immune status; it reliably increased the count of T-helpers (CD4+) and of natural
      killers (CD16+) and it induced the phagocyte activity of neutrophils.

PMID- 15573736
TI  - [Tramadol hydrochloride in the treatment of postoperative shivering].
AB  - A double blind study of the therapeutic effect of the opioid tramadol
      hydrochloride (Gruenenthal, Germany) in the treatment of postoperative trembling
      was undertaken in 2 groups of patients (50 patients in each) versus that of
      placebo. The results obtained denoted that tramadol at 1-2 mg/kg arrested
      completely the postoperative trembling or cut significantly its intensity in 49
      (98%) patients. Such high efficiency of tramadol as compared to that of other
      opioids can be explained by its dual mechanism of action. The dependence of an
      effective tramadol dose on intensity of shivering and on degree of impaired
      temperature hemostasis was demonstrated. A comparison of hemodynamic parameters
      observed before and after the administration of tramadol did not reveal any
      valuable changes in arterial pressure or cardiac beat rate. Mildly intensified
      sedation was registered in 17 patients, which is typical of all opioids.

PMID- 15573737
TI  - [Respiratory contour filters for artificial pulmonary ventilation used in
      intensive care units].

PMID- 15573738
TI  - [Anesthesiologic management in obstetrics: state of the problem and perspectives
      (Part 1)].

PMID- 15573739
TI  - [beta-Adrenoblockers in anesthesiology and intensive care].

PMID- 15573740
TI  - How should we manage patients with "platinum-sensitive" recurrent ovarian cancer?
AB  - Decisions about the treatment of recurrent ovarian cancer are usually based on
      the treatment-free interval. Patients relapsing with an interval of more than six
      months are usually retreated with platinum-based chemotherapy. Non platinum drugs
      (such as paclitaxel, gemcitabine, liposomal doxorubicin or topotecan) are also
      active in relapsed disease. A high response rate is consistently seen with
      combinations of platinum and these drugs in phase II trials. ICON 4, the first
      large-scale randomised trial in 'platinum-sensitive' relapsed ovarian cancer
      demonstrated a survival benefit for using platinum-based therapy in combination
      with paclitaxel. More studies are needed to explore other combinations of
      treatment in this group of women as the choice and timing of second-line therapy
      needs to take account of the benefits and toxicity of treatment.

PMID- 15573741
TI  - Update on Gynecologic Oncology Group (GOG) trials in ovarian cancer.
AB  - The Gynecologic Oncology Group (GOG) has conducted a series of randomized trials
      in advanced ovarian cancer patients, both with early-stage disease (FIGO stages I
      and II) and advanced-stage disease (FIGO stages III and IV). In patients with
      early-stage disease, the current standard of therapy is three cycles of
      paclitaxel and carboplatin-based combination chemotherapy. In patients with
      advanced-stage ovarian cancer, the GOG standard is six cycles of the same
      regimen. The GOG has also performed prospective randomized trials of
      consolidation and maintenance therapy with intraperitoneal (IP) radioisotomes and
      additional cycles of paclitaxel, respectively. Neither of these modalities has
      shown improvement in survival. In addition, the GOG has performed randomized
      trials of IP chemotherapy, and while it has been demonstrated that the regimens
      that included IP cisplatin led to improved outcomes, the toxicity of this
      approach has precluded widespread acceptance of this modality. Currently, the GOG
      is performing additional pilot studies to evaluate less toxic IP regimens. The
      GOG has also been at the forefront of developing new combination chemotherapy
      regimens based on the activity of second-line agents, such as topotecan,
      gemcitabine, and encapsulated doxorubicin. The GOG is also exploring molecular
      targeted therapies in phase II trials with the goal of ultimately incorporating
      biological therapies in newly diagnosed patients with advanced disease.

PMID- 15573742
TI  - First-line therapy for ovarian carcinoma: what's next?
AB  - Based on results from large, randomized trials conducted over the last 25 years,
      the current standard of care for newly diagnosed advanced (FIGO stage III-IV)
      ovarian carcinoma is surgical bulk reduction followed by six cycles of paclitaxel
      plus carboplatin. This approach has resulted in an enhanced response rate and
      clinical complete response rate, an improved progression-free survival, an
      increase in survival, and more long-term survivors. Despite these results, the
      overall frequency of relapse and hence need for second-line therapy is 62%.
      Ongoing and future studies focus or will focus on four major themes: dose
      intensity through the use of intraperitoneal chemotherapy in selected patients,
      addition of a third cytotoxic agent to front line therapy, addition of a targeted
      or biologic agent to front-line therapy, and the development of effective
      maintenance or consolidation therapy. The current standard of care for patients
      who present with limited (FIGO stage I-II) ovarian carcinoma is the use of
      prognostic factors to classify the patient as at low risk or high risk for
      recurrence. High risk features include: grade 2 or 3 disease, disease on the
      surface of the ovary, disease outside the ovary, positive peritoneal cytology, or
      the presence of ascites. Any one high risk feature makes the patient high risk
      for recurrence. Patients at low risk require surgical resection only, whereas
      those at high risk for recurrence require adjuvant therapy. Ongoing studies
      evaluate the duration of therapy and the potential value of anti-angiogenic
      agents in those patients at high risk for recurrence. Future directions point to
      the evaluation of targeted or biologic agents in high risk patients. At present,
      there is no evidence that any approach constitutes an effective screening test.
      Studies of serum markers, transvaginal sonography, and serum proteomic profiles
      have failed to establish any of these techniques as an effective tool for early
      diagnosis. An overview of current management and its basis will be followed by a
      discussion of the rationale for both current and potential future trials.

PMID- 15573743
TI  - Novel agents in epithelial ovarian cancer.
AB  - The gold standard chemotherapy for previously untreated patients with ovarian
      cancer is currently a combination of taxane and platinum. However, most patients
      still suffer relapse, and less than 20% of the patients with stage III or IV
      disease survive long term. With more advanced technology, newer cytotoxic agents
      have been identified and are currently being tested in patients with ovarian
      cancer. Recent advances in the understanding of ovarian cancer biology have also
      led to the identification of multiple molecular targets that may soon change the
      standard treatment of ovarian cancer. Several of these targeted agents have
      entered clinical trials. Small molecular-weight inhibitors, monoclonal
      antibodies, antisense therapy, and gene therapy are all being evaluated alone and
      in combination with cytotoxic chemotherapy. Several of these cytotoxic and
      targeted therapies are reviewed here. Ultimately, the success of ovarian cancer
      therapy lies not just in the availability of new agents but in the ability to
      identify patients with biomarkers that may predict their response to these
      agents.

PMID- 15573744
TI  - [Study on in vitro and in vivo antibacterial activity of pheromonicin-SA].
AB  - OBJECTIVE: To evaluate the bactericidal activity of pheromonicin-SA (Ph-SA) via
      routine in vitro/in vivo measurement. METHODS: Minimal inhibitory concentration
      (MIC50 and MIC90) of Ph-SA were evaluated via in vitro double-dilution assay with
      69 strains pathogenic bacteria and via intraperitoneal infected mice with
      intravenous Ph-SA treatment. RESULTS: In vitro data showed that bactericidal
      activity of Ph-SA was approximately 12 times greater, on a molar basis, than that
      of vancomycin. In vivo data showed that bactericidal activity of Ph-SA was
      approximately 59 times greater than that of vancomycin. CONCLUSION: The results
      suggest that Ph-SA may be of potential value as antibiotic against methicillin
      resistant Staphylococcus aureus (MRSA).

PMID- 15573745
TI  - [Construction and prokaryotic expression of a recombinant immunotoxin fused with
      mouse interleukin 18 and truncated Pseudomonas exotoxin].
AB  - OBJECTIVE: To construct a new recombinant immunotoxin expression vector by fusion
      of mouse interleukin 18 (mIL-18) gene and a truncated form of A (PE38) gene, and
      examine the expression of IL-18-PE38 fusion protein in Escherichia coli. METHODS:
      mIL-18 cDNA was cloned from mouse liver tissue through reverse transcription
      polymerase chain reaction (RT-PCR). The mIL-18 cDNA was subcloned into a PE38
      gene inserted fusion protein expression plasmid. The recombinant vector was
      identified by restriction endonucleases digestion, PCR and DNA sequencing. After
      transformed into E. coli BL21 and induced by IPTG, the expressed product was
      obtained and detected the molecular weight and specificity by SDS-PAGE and
      Western-blotting. RESULTS: The new recombinant immunotoxin expression vector was
      constructed successfully. The IL-18-PE38 fusion protein was expressed in E. coli
      BL21, and the molecular weight of the expression product was identical to the
      expected value. In addition, the protein expressed could react with the specific
      antibody against mIL-18. CONCLUSION: IL-18-PE38 recombinant immunotoxin
      expression vector will provide the basis for study on the targeted cytotoxic
      activity to Th1 cell and may have some potential value in the treatment of
      autoimmune disease and T cell leukemias.

PMID- 15573746
TI  - [The mechanism of anti-tumor immune response against mouse melanoma to xenogeneic
      vaccination].
AB  - OBJECTIVE: To investigate the immunological mechanism for inhibiting melanoma
      growth in mouse by vaccination with xenogeneic melanocytes. METHODS: Xenogeneic
      vaccine was prepared from pig eye melanocytes. By means of indirect ELISA the
      antibodies against pig melanocytes and B16 melanoma cells in immunized mice sera
      were detected and the immunoglobulin subclass were analyzed. Then after
      purification, the immunoglobulins were used for the inhibition of cell
      proliferation in vitro. Analyses of cross-reactive antigen in both pig
      melanocytes and B16 melanoma cells were performed by Western blot. Xenogeneic
      vaccine was used before B16 melanoma challenge in C57 BL/c mice and then the
      growth of tumor was monitored. Meanwhile, other mice immunized with xenogeneic
      vaccine were depleted of NK cells or CD4+ or CD8+ T lymphocytes. RESULTS: The
      antibodies against pig melanocytes and B16 melanoma cells in mice sera were not
      detected by indirect ELISA until 2 weeks after first xenogeneic vaccination, and
      after the first finding, the antibody titers increased with the time of
      immunization. The anti-tumor activity and production of autoantibodies,
      conspicuously those of the elevated IgG, could be abrogated by the depletion of
      CD4+ T lymphocytes. The cross-reactive antigen with 180 kda protein in both pig
      melanocytes and B16 melanoma cells was confirmed. Xenogeneic vaccination resulted
      in inhibition of tumor growth in 90% of the immunized mice. The protective immune
      response elicited in this fashion was dispelled in the mice depleted of CD4+ T
      lymphocytes. However this response was found in 70% of the mice depleted of CD8+
      T lymphocytes, and the depletion NK cells did not influence the anti-tumor effect
      of the vaccine. CONCLUSION: The anti-tumor immune response is capable of
      inhibiting melanoma growth; both humoral immunity and cellular immunity could be
      induced by xenogeneic melanocytes vaccination. This immune response is mainly
      mediated by CD4+ T lymphocytes.

PMID- 15573747
TI  - [Cloning the gene of rat premature nerve growth factor and constructing its
      eukaryotic expression vector pEGFP-NGF].
AB  - OBJECTIVE: To clone the entire coding sequence of rat premature nerve growth
      factor (NGF) beta subunit and construct its eukaryotic expression vector.
      METHODS: The gene of premature nerve growth factor (NGF) beta subunit was
      amplified by RT-PCR from SD rat brain. RT-PCR product was ligated into pMD 18-T
      Vector, the recombinant plasmid was identified by the restriction enzymes, PCR
      and DNA sequence analysis. Then the gene of premature nerve growth factor (NGF)
      beta subunit was cloned into the eukaryotic expression vector pEGFP-N1. The
      recombinant plasmid pEGFP-NGF was identified by the restriction enzymes analysis.
      RESULTS: The DNA sequence was identical to the published sequence encoding NGF
      gene, the restriction enzymes mapping product of the recombinant plasmid pEGFP
      NGF was nearly 750 bp which matched the expected size. CONCLUSION: The entire
      coding sequence of premature nerve growth factor (NGF) beta subunit was
      successfully cloned and its eukaryotic expression vector pEGFP-NGF was
      constructed, which will provide the basis for studying the gene of NGF.

PMID- 15573748
TI  - [Study on chronic toxicity to rats of implantation of super-high molecular weight
      polylactate].
AB  - OBJECTIVE: To make sure whether super-high molecular weight polylactate is toxic
      to the body after it has been implanted into the body for a long period. METHODS:
      We implanted super-high molecular weight polylactate into the rats and took the
      specimens of blood at 3, 6, 9, 12 months after the operation. The changes of
      proteins, electrolyte, enzyme and other indices were observed. At the same time,
      the tissue around the implants were taken out to carry out the histological
      observation. RESULTS: At 3, 6, 9, 12 months after the operation, the levels of
      albumin, globulin, total bilirubin, direct bilirubin, triglyceride, glucose, K+,
      Na+, Cl-, Ca2+, alkaline phosphatase, glutamic-pyruvic transaminase in the blood
      plasma were all in the normal range; there were no significant differences
      between the experimental group and the control group. The level of lactate
      dehydrogenase increased slightly, but there was no statistically significant
      difference between the experimental group and the control group. There were no
      non-reversible immune rejection around the implants in the histological
      observation. CONCLUSION: Super-high molecular weight polylactate is not toxic to
      the body after it has been implanted into the animals for a long period.

PMID- 15573749
TI  - [Sensitivity comparison of DNA damage and repair capacity in TK6 and WTK1 cells].
AB  - OBJECTIVE: Explore the mechanisms of DNA damage and repair capacity in TK6 and
      WTK1 cells that are derived from the same parental cell line WI-L2 (tk+/+) human
      diploid lymphoblastoid cells but are different in their p53 gene status. METHODS:
      The TK6 and WTK1 cells treated with H2O2 were detected by single cell gel
      electrophoresis. Then a comparison was made on the comet cell rate, comet cell
      tail length and p53 protein expression level between TK6 and WTK1. RESULTS: TK6
      was more sensitive to DNA damage and its repair capacity was more quick and
      effective when compared with WTK1. Both TK6 and WTK1 cells showed effective post
      damage repair capacity in incubation time of 0.5 h to 1 h. The background level
      of P53 protein in WTK1 was higher than that in TK6, but the level of P53 protein
      in H2O2-treated TK6 increased significantly higher than that in H2O2-treated
      WTK1. CONCLUSION: TK6 and WTK1 cells serve as a good biological experiment system
      for DNA damage sensitivity and repair capacity researches in the field of
      toxicology. TK6 is more sensitive to DNA damage, and it increases faster and
      higher than WTK1 after DNA being damaged. A possible explanation is that TK6 cell
      is of the p53 gene wild-type and WTK1 cell is of the mutant-type and they make
      different responses to the same chemical.

PMID- 15573750
TI  - [Time course of the disruption of rat's thyroid function by pesticide N'N
      methylene-bis].
AB  - OBJECTIVE: To study the effect of pesticide N'N-methylene-bis on thyroid function
      in rats, and the time-effect relationship. METHODS: N'N-methylene-bis
      dimethylsulfoxide solution was administered to rats by gavage at a dose of 50
      mg/kg body weight for 1, 3, and 5 days respectively. The rats in the control
      group were given solvent dimethylsulfoxide by oral gavage at the same volume. All
      animals were sacrificed 1 day after the last dosage, and the levels of FT4 and
      TSH in serum were measured by radioimmunoassay. The histological changes of
      thyroid gland were observed, and the expression of PCNA in thyroid was detected
      by immunohistochemistry. RESULTS: Compared with the solvent control group, the
      serum FT4 level in rats given N'N-methylene-bis for 3 days significantly
      decreased, while the TSH level significantly increased in the 3 d and 5 d groups
      (P<0.05). Hyperplasia of thyroid follicular epithelium was observed in the 3 d
      and 5 d groups. PCNA positive cells in thyroid of the 3 d and 5 d groups were
      significantly higher than that of control (P<0.05). CONCLUSION: The effect of N'N
      methylene-bis on the level of serum FT4 and TSH in rats appeared on the 2nd or
      3rd day of the experiment. Histopathologic examination showed thyroid gland
      proliferation of follicular epithelium within 3 days. The combined use of
      serologic test and histopathologic examination for screening thyroid hormone
      disruptors may be an effective method.

PMID- 15573751
TI  - [The effects of losartan on pulmonary arterial collagen and AT1 in chronic
      hypoxic rats].
AB  - OBJECTIVE: To investigate the effects of losartan on pulmonary arterial collagen
      and AT1 in chronic hypoxic rats. METHODS: Thirty male SD rats were randomly
      divided into three groups: control group, hypoxic group and therapeutic group.
      The animal model of pulmonary hypertension was established by exposing the rats
      to normabaric hypoxic conditions for three weeks. Then, the therapeutic group was
      given losartan for two weeks. We measured the expression of Collagen I, III and
      AT1 in arterioles by means of immunohistochemistry. RESULTS: The positive degree
      of Collagen I in pulmonary arterioles in the hypoxic group was higher than that
      in the control group [(1.5202+/-0.069) vs (1.1324+/-0.071), P<0.01]; but in the
      therapeutic group it was lower than that in the hypoxic group [(1.1637+/-0.062)
      vs (1.5202+/-0.069), P<0.01]. There was no significant difference in collagen III
      and AT1 among the three groups (P>0.05). CONCLUSION: Losartan could reduce
      pulmonary arterial collagen I expression, it may be one of the therapeutic
      mechanisms on hypoxic pulmonary hypertension of losartan.

PMID- 15573752
TI  - [Activation of nuclear factor-kappa B and expression of cytokine in intestinal
      epithelia stimulated by TNF-alpha].
AB  - OBJECTIVE: To investigate the effect of nuclear factor-kappa B activation on
      proinflammatory cytokine expression in intestinal epithelia when intestinal
      epithelia are in inflammatory condition. METHODS: Colonic adenocarcinoma HT29
      cells were cultured in wells and TNF-alpha (10 ng/ml) was added into half of the
      wells. The supernatants were collected and measured for IL-8 after 3 hours,
      nuclear factor-kappaB (NF-kappaB) P65 and IL-8 mRNA were also examined by Western
      blotting and RT-PCR respectively. RESULTS: It was found that in the condition of
      no stimuli, there is little IL-8 mRNA expression of HT29 cells, P65 is seldom in
      HT29 cells' nuclei, and the concentration of IL-8 in supernatant is just 172
      ng/L. However, after being stimulated by TNF-alpha, a lot of P65 expression in
      nuclei and a large number of IL-8 mRNA expression of HT29 cells are shown and the
      concentration of IL-8 in supernatant (639 ng/L) is significantly higher than that
      of control (P<0.01). CONCLUSION: The activation of nuclear factor-kappa B
      modulates the expression of some proinflammatory cytokine in intestinal
      epithelia, and regulates epithelia function in inflammatory reaction.

PMID- 15573753
TI  - [Comparison of hepatic protein synthesis function between Banna Minipig Inbred
      Line and human].
AB  - OBJECTIVE: This is a research aimed at comparing the hepatic protein synthesis
      function of Banna Minipig Inbred Line (BMI) with that of human so as to evaluate
      the possibility of porcine liver replacement of human counterpart. METHODS: The
      venous blood samples from BMI and volunteer participants were collected. The
      albumin and total protein in the separated sera were tested using Beckman delta
      CX7 autoanalyzer, and serum protein electrophoresis was performed. RESULTS: No
      significant differences in albumin and in the percentage and concentration of
      globulins synthesized in liver (alpha1-, alpha2- and beta-globulin) between BMI
      and human were observed. The percentage and concentration of gamma-globulin
      synthesized in the lymphocytes of BMI were significantly higher than those of
      human. CONCLUSION: The above findings suggested the similarity between BMI liver
      and human liver in respect to albumin and alpha, beta-globulin synthesis.

PMID- 15573754
TI  - [The T cells activated by dendritic cells derived from AML cells: a study of
      their cytotoxic effect on autologous AML cells].
AB  - OBJECTIVE: To culture dendritic cells (DCs) from human acute myeloid leukemia
      (AML) cells, and to observe the cytotoxic effect of the T lymphocytes that are
      activated by DCs pulsed with leukemic antigen peptides (LAP) or LAP-heat shock
      protein 90 (HSP90) on autologous AML cells. METHODS: Mononuclear cells (MNC) were
      isolated from peripheral blood (PB) and bone marrow (BM) of patients with AML by
      density gradient centrifugation; DCs were induced from MNC of PB in a special
      culture system including recombinant human granulocyte-monocyte colony
      stimulating factor (rhGM-CSF), interleukin-4 (rhIL-4) and tumor necrosis factor
      alpha (TNF-alpha) for 7-14 days. These DCs were identified by morphology and
      immunophenotype studies; LAP were obtained by repeatedly freezing and thawing AML
      cells respectively. DCs were pulsed with LAP and LAP-HSP90 compounds
      respectively. The cytotoxity of T lymphocytes activated by antigen pulsed DCs on
      autologous AML cells was measured in vitro by the lactate dehydrogenase-release
      assay. RESULTS: After 7-14 days' culture, (6-11) x 10(4) DCs were obtained from 1
      x 10(6) MNC of PB in 3 AML cases. The cytotoxity rates of T lymphocytes, from 3
      AML cases, activated by DCs pulsed with LAP and LAP-HSP90 compounds were (35.33+/
      9.04)% and (62.07+/-8.29)% respectively. CONCLUSION: Effective cytotoxity of T
      lymphocytes to the autologous leukemia cells can be induced by DCs pulsed with
      LAP and LAP-HSP90 compounds respectively, but the effectiveness induced by the
      latter is more powerful than that induced by the former.

PMID- 15573755
TI  - [Differentiation and apoptosis of NB4 cells synergistically induced by Tanshinone
      II A and all-trans retinoic acid].
AB  - OBJECTIVE: To evalutate the synergistic effects of Tanshinone II A combined with
      all-trans retinoic acid (ATRA) on the differentiation and apoptosis of human
      acute promyelocytic leukemia (APL) cell line (NB4). METHODS: The NB4 cells were
      treated with 0.5 microg/ml Tanshinone II A combined with 0.5 microg/ml, 0.25
      microg/ml and 0.125 microg/ml ATRA respectively in culture. Cells differentiation
      was demonstrated by morphology and NBT reduction assay. The expression of CD11b
      and CD33, cell cycle and apoptosis induced by these drugs were measured by flow
      cytometry (FCM). RESULTS: The proliferative inhibition rate of the combination of
      Tan II A with ATRA was much higher. The differentiated cells accounted for over
      90 percent, among them the band forms and neutrophils constituted more than 65
      percent. NBT reduction and CD11b expression were much higher, and expression of
      CD33 was lower than that of Tan II A or ATRA alone (P<0.01). FCM analysis also
      showed that combination of Tan II A with ATRA arrested NB4 cells in G0/G1 phase
      and induced significantly apoptosis of NB4 cells (P<0.01). There were no
      significant dose dependent effects induced by ATRA in combination with Tan II A
      at 0.125 microg/ml to 0.5 microg/ml on differentiation and apoptosis of NB4
      cells. CONCLUSION: The combination of Tan II A with ATRA has synergistic effects
      on differentiation and apoptosis of NB4 cells. The effects do not increase with
      the dosage escalation of ATRA.

PMID- 15573756
TI  - [Research on the growth inhibition of T47D cell and reversion of p16
      hypermethylation by CDP].
AB  - OBJECTIVE: To inquire into the mechanism of CDP (a purified component of Chinese
      crude drug) in inhibiting the breast cancer T47D cell growth. METHODS: T47D cells
      were treated with different concentration of 5-azacytidine (5-aza-CR) and CDP for
      several days. The growth rate was assessed by cell proliferation experiment (MTT
      colorimetric assay). The changes in apoptic peak and cell cycle distribution were
      detected by flow cytometry (FCM). The levels of methylation and unmethylation
      status of p16 were detected by methylation specific PCR (MSP). RESULTS: After
      treatment with the two drugs, the cell growth rate decreased in a dose and time
      dependent manner (P<0.05). The cell cycle was influenced by the well-chosen
      concentration of 5-aza-CR (2 micromol/L) and CDP (50 micromol/L): the cell number
      increased from 65.1% to 71.3%, 84.3% in G0/G1 phase and decreased from 19.4% to
      14.3%, 7.2% in S phase. Demethylation on p16 gene occurred after treatment with
      any of the two drugs for 6 days. CONCLUSION: CDP can reverse p16 hypermethylation
      and may hence inhibit the proliferation of tumor cells.

PMID- 15573757
TI  - [The synergistic effects of docetaxol and retinoic acid on prostate cancer cell
      line PC-3].
AB  - OBJECTIVE: To observe the synergistic effects of docetaxol and retinoic acid on
      prostate cancer cell line PC-3 in vitro and in vivo. METHODS: Cell morphology,
      MTT, flow cytometry, immunocytochemical method were used to observe the effects
      of 10(-6) mol/L, 10(-7) mol/L, 10(-8) mol/L docetaxol and 10(-5) mol/L, 10(-6)
      mol/L, 10(-7) mol/L retinoic acid on prostate cancer cell line PC-3 in single or
      synergistic administration ways for 24 and 48 hours in vitro. Male BALB/C-nu mice
      with PC-3 prostate cancer cell lines were treated by docetaxol and retinoic acid
      singly or synergistically in vivo. Serum PSA of mice, weights of mice and PSA
      expression in xenograft tumors of mice by immunohistochemical method were
      measured. RESULTS: Above 10(-6) mol/L retinoic acid enhanced the growth
      suppression (suppression ratio > or = 69.2%, P<0.01), apoptosis (Apoptosis ratio
      > or = 23.8%, P<0.05) and down-regulation of the expression of cyclin D1
      (expression ratio < or = 14.2%, P<0.05) induced by above 10(-7) mol/L docetaxol
      in PC-3 cells. Retinoic acid changed the ratio of G2/M phase induced by docetaxol
      from 70.3% to 54.6%, and reversed the G2/M arrest partially (P<0.05). Mean serum
      PSA of mice [(43+/-11) ng/ml], weight of xenograft tumors [(2.8+/-0.4) g] and PSA
      expression in tumors [(26+/-3.2)%] with PC-3 prostate cancer cell lines of nude
      mice were decreased significantly in docetaxol combined with retinoic acid group
      than in control group except weight of mice [(20.3+/-1.1) g]. CONCLUSION:
      Retinoic acid can enhance the growth suppression and apoptosis induced by
      docetaxol in synergistic way in vitro and in vivo, thus showing their great
      potential in the treatment of androgen-independent carcinoma of prostate.

PMID- 15573758
TI  - [Effect of quercetin on the signal pathway of TGFbeta1 in activated hepatic
      stellate cells].
AB  - OBJECTIVE: To investigate the effect of quercetin on the expression of connective
      tissue growth factor (CTGF) and fibronectin (FN) in hepatic stellate cells (HSCs)
      stimulated with transforming growth factor (TGF)beta1. METHODS: HSCs of rat were
      isolated by in situ perfusion and gradients centrifugation; the activated HSCs
      were incubated with quercetin (10(-9)-10(-5) mol/L) for 24, 48 and 72 h. TGFbeta1
      was detected by flow cytometry. The expression of CTGF was detected by reverse
      transcription-polymerase chain reaction (RT-PCR), and then FN was detected by
      immunohistochemistry. RESULTS: Quercetin (10(-8) to 10(-5) mol/L) inhibited the
      expression of TGFbeta1 in HSCs. TGFbeta1 expression decreased after the HSCs
      being incubated with quercetin (10(-7) mol/L) for 48 h (mean fluorescence:
      13.33+/-2.44 and 18.08+/-2.54, t=16.52, P<0.01). TGFbeta1 increased the
      expression of CTGF mRNA in HSCs, but this effect was abrogated by quercetin (10(
      7) mol/L) within 72 h. Quercetin (10(-7) mol/L) significantly inhibited the
      expression of FN in HSCs. CONCLUSION: Quercetin may have an inhibitory effect on
      the signal pathways of TGFbeta1, including the expression of TGFbeta1, FN and
      CTGF.

PMID- 15573759
TI  - [Effects of leptin on development of mouse preimplantation embryos in vitro].
AB  - OBJECTIVE: To investigate the effects of leptin on development of mouse
      preimplantation embryos in vitro. METHODS: (1) Groups of 2-cell stage embryos
      randomly selected were placed in drops of CZB medium with or without recombinant
      leptin (10, 50, 100 and 500 ng/ml) and were cultured to the hatched blastocyst
      stage, and then embryo-transfer was carried out and the implantation rate was
      observed and determined. (2) Groups of 2-cell stage embryos randomly selected
      were placed in drops of leptin free CZB medium and cultured to morula stage. Then
      we changed the medium, randomized the embryos into CZB medium with or without
      recombinant leptin (10, 50, 100 and 500 ng/ml), and cultured them to the hatched
      blastocyst stage. RESULTS: Addition of leptin to embryo culture media promoted
      the development from 2-cell stage embryo to morula, blastocyst and hatched
      blastocyst and improved the implantation rate. Leptin at 0, 10, 50 ng/ml
      concentrations caused a dose-dependent promotion, nevertheless Leptin at even
      higher concentrations (100 and 500 ng/ml) only brought on the same promotion as
      what the Leptin at concentration of 50 ng/ml did (P>0.05). Addition of leptin to
      embryo culture media seemed to have no effects on the in vitro development from
      morula to blastocyst and hatched blastocyst. CONCLUSION: Leptin plays an
      important role in the development of preimplantation embryo. It can promote
      embryo development and embryo implantation.

PMID- 15573760
TI  - [Study on association between aldosterone synthase gene polymorphism and the left
      ventricular structure and function of patients with dilated cardiomyopathy in
      China].
AB  - OBJECTIVE: To investigate the association between a -344 C/T polymorphism of
      aldosterone synthase gene (CYP11B2) and the left ventricular structure and
      function of patients with dilated cardiomyopathy (DCM) in China. METHODS: Eighty
      nine patients with DCM were genotyped by PCR-RFLP, and were divided into TT, TC,
      CC and TT+CC four groups by their genotypes, respectively. Left ventricular
      structure and function were assessed with echocardiography. RESULTS: There was no
      significant difference between four groups in left ventricular diameters, mass
      and ejection fraction in patients with DCM. CONCLUSION: The data were not in
      favor of a significant association between the aldosterone synthase gene CYP11B2
      and the left ventricular structure and function in patients with DCM.

PMID- 15573761
TI  - [Polymorphisms and species specificity of D2S2944 and D1S2134 loci in Chinese Han
      population in Chengdu].
AB  - OBJECTIVE: To obtain the data of polymorphism distribution of the two STR loci
      D2S2944, D1S2134 in Chinese Han population in Chengdu and evaluate their
      usefulness in the field of forensic science. METHODS: PCR, polyacrylamide gel
      electrophoresis (PAGE) and silver staining were used to analyze 120 unrelated
      individuals of Chinese Han ethnic group in Chengdu. Fourteen different animals:
      monkey, pig, dog, bull, goat, chicken, duck, fish, cat, rabbit, Guinea pig,
      mouse, eel and frog were selected as controls in this study for evaluating the
      species specificity of the two STR loci. RESULTS: Eight alleles and twenty-two
      genotypes were found in D2S2944. The observed heterozygosity (h), discrimination
      power (DP), polymorphism information content (PIC), chance of paternity exclusion
      power (EP) were 0.824, 0.925, 0.78, 0.644 respectively. Ten alleles and twenty
      six genotypes were observed in D1S2134. The h, DP, PIC and EP were 0.769, 0.920,
      0.79, 0.543 respectively. The genotype distributions of the two loci were
      analyzed by some related software and no deviation from the Hardy-Weinberg
      equilibrium was observed. Evaluated by way of using different animals as
      controls, the two STR loci of human beings were found to have good specificity.
      CONCLUSION: These data indicate that D1S2134 and D2S2944 are of good
      polymorphism, high EP and DP, and can be applied as the candidate genetic marks
      to forensic parentage testing and identification. The methods to analyze them are
      simple, dependable and repeatable.

PMID- 15573762
TI  - [Association of psychosocial factors and platelet 5-HT with peptic ulcer].
AB  - OBJECTIVE: To scrutinize the association of psychosocial factors especially
      emotional factors with peptic ulcer. METHODS: Eighty-nine peptic ulcer patients
      and 50 normal controls were investigated by means of questionnaires for
      personality, alexithymia, social support, life events, and their platelet 5-HT
      levels were determined. RESULTS: By comparison with normal controls, the peptic
      ulcer patients had: (1) higher scores on the subscales such as Hs, D, Pt, Sc and
      Hy of personality; (2) Higher scores on HAMA, HAMD and Toronto alexithymia scale
      (TAS); (3) Significantly lower platelet 5-HT concentration. And in the ulcer
      patients who were not infected with HP (called HP negative), the area of their
      ulcer was found to have a positive correlation with HAMA and TAS scores (r=0.74,
      P<0.01; r=0.45, P<0.05). CONCLUSION: (1) There was a correlation between the
      onset of peptic ulcer and personality or manner of emotional expression. (2)
      There may be two subtypes of ulcer patients: one of it may be due to HP infection
      and the other may be more closely associated with negative emotion and manner of
      emotional expression; for the latter one, anxiolytics deserve to be included in
      the routine treatments.

PMID- 15573763
TI  - [Acquisition of Mutans streptococci by children of 3-4 years with possible source
      of the pathogen from their mothers].
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of Mutans
      streptococci (MS) in children of 3-4 years and thus reveal the relationship
      between the children's acquisition of MS and their mothers' pathogen. METHODS:
      Fifty mother-child pairs were selected, examined and divided into three groups
      according to the children's caries. MS in plaque and mothers' salivary samples
      were detected by MSB medium. Then 200 MS strains from 20 mothers-children were
      analyzed by AP-PCR. RESULTS: Acquisition of MS was identified in 37 of 50
      children (74%), including 11 of 24 caries-free children and all 26 children with
      caries. The difference was significant (P<0.01). Genotypes showed that 16 of 37
      children (43.2%) had the same fingerprint as their mothers'. The level of MS
      identified in mothers' salivary sample was lower than that in mothers' plaque
      sample (32% and 56%). CONCLUSION: These results suggested that caries in children
      of 3-4 years are closely related with MS acquisition. Mothers are still their
      important source of MS. The sensitivity of mothers' salivery samples is much
      lower than that of plaque samples in studying the transmission of MS.

PMID- 15573764
TI  - [The protective effect of dachuanxiongwan on the rats with focal cerebral
      ischemia and reperfusion].
AB  - OBJECTIVE: Studying the protective effect of dachuanxiongwan (DCXW) on the rats
      with focal cerebral ischemia and reperfusion. METHODS: The ischemia and
      reperfusion model was established by blocking the rat's middle cerebral artery
      with a pre-set nylon thread and removing it from the internal carotid artery 2
      hours after occlusion. 20 healthy male Sprague-Dawley rats following middle
      cerebral artery occlusion (MCAO) were randomly divided into two groups: Group A,
      transient ischemia, for control; Group B, transient ischemia treated with DCXW
      via gavage, 4.13 g/kg x d, twice a day for 3 days, while group A being given the
      same volume of saline. Seventy-two hours after reperfusion, the neurological
      function of all rats was evaluated according to Longa, and the rats were
      sacrificed. All the samples of cerebrum were processed and embedded in paraffin
      and cut into sections. The sections were stained with Hematoxylin & Eosin to
      measure the infarction volume and evaluate the effects of DCXW. RESULTS: The
      grade of neurological function of the treatment group (1.5+/-0.71) was lower than
      that of the control group (2.3+/-0.82), there was a statistically significant
      difference between the two groups (P=0.032); the infarction volume of the
      treatment group was smaller than that of the control group, there was a
      statistically significant difference between the two groups (P=0.000).
      CONCLUSION: The findings suggest that DCXW has a protective effect on the
      cerebrum undergoing ischemia and reperfusion.

PMID- 15573765
TI  - [The effect of electroacupuncture on the weakening of CPP of morphine dependence
      rats and the mechanism therein involved].
AB  - OBJECTIVE: To address the research questions whether electroacupuncture can
      weaken the CPP of morphine dependence rats and whether the neurobiological
      mechanism for control of anxiety is related to the transcription of DBI mRNA.
      METHODS: Twenty-four SD rats were randomly divided into the control group,
      electroacupuncture group and morphine group. After the CPP model was constructed.
      The time of CPP was examined on the 5th and 10th day as the interventional
      electroacupuncture was instituted. The total RNA was extracted from the brain of
      sacrificed rat and was defected by use of RT-PCR. RESULTS: The CPP time of the
      electroacupuncture group was significantly decreased on the 5th and 10th day
      after abstinence (P<0.05). The transcription of the DBI mRNA of the
      electroacupuncture group was obviously lower than that of the morphine group
      (P<0.05), and there was no difference between the electroacupuncture group and
      control group. CONCLUSION: Electroacupuncture can weaken the CPP of the morphine
      dependence rats, and the neurobiological mechanism may be related to the
      electroacupuncture-induced transcription of DBI mRNA.

PMID- 15573766
TI  - [A study on expression of hsp70 mRNA in the early stage of diffuse brain injury
      in rats].
AB  - OBJECTIVE: To evaluate the changes of hsp70 mRNA in neuron and glia of rat
      suffering early diffuse brain injury. METHODS: SD rats were used in the
      replication of the animal pattern of diffuse brain injury. In situ hybridization
      technique and image analysis technique were applied in detecting the hsp70 mRNA
      in the rat's cerebral cortex, thalamus and brain stem. RESULTS: The signal
      intensity of hsp70 mRNA could be detected in 5 minutes after brain injury;
      subsequently, it attained to the summit at 6 hours and declined at 12 hours after
      brain injury. CONCLUSION: The above data suggest that hsp70 mRNA is useful for
      the diagnosis of early diffuse brain injury and for distinguishing the postmortem
      injury from antemortem injury.

PMID- 15573767
TI  - [Transfection and expression of recombinant human beta-defensin-2 gene in insect
      cells].
AB  - OBJECTIVE: This study was conducted to determine the feasibility and relevant
      technique itinerary for the production of hBD-2 with Baculovirus Expression
      Vector System (BEVS). METHODS: The full hBD-2/His cDNA was amplified from
      rpcDNA3.1/hBD-2/myc-His by using PCR with a pair of primers (hBD2p10 and hBD2p11)
      and was inserted into the MCS of transfer vector: pAcGHLT-A. AcNPV DNA and
      rpAcGHLT-A/hBD-2/His were co-transfected into Sf21 cells. Recombination would
      take place within the Sf21 cells between the homologous regions in the transfer
      vector and AcNPV DNA. After 5 days of co-transfer, both supernatant of the
      experimental cells and positive control cells were collected. Sf21 cells were
      infected with virus rAcNPVhBD-2/His and then determined by end-point dilution
      assay. The expression of hBD-2/His in both cell lysate and supernatant was
      analyzed by western blot with specific 6 poly-histamines antibody. RESULTS: Both
      enzyme cutting result and sequence analysis showed that recombinant hBD-2 with C
      terminal of bi-tags of myc and 6xHis had been inserted into the transfer vector
      of BEVS system correctly, and recombinant transfer vector rpAcGHLT-A/hBD-2/His
      had been constructed successfully. End-point dilution assay proved that
      recombinant virus rAcNPVhBD-2/His had been acquired. Western blot revealed that
      lysate of Sf21 cells transfected by rAcNPVhBD-2/His showed a band of relative
      moleculal mass about 47.5 x 10(3) which implied that a fuse peptide of hBD-2/His
      with up-stream of GST tag, 6xHistag, protein kinase A site and thrombin cleavage
      had expressed. The culture supernatant showed two bands of relative moleculal
      mass about 40 x 10(3) and 30 x 10(3), which were inferred to be the proceeded
      products of the fuse peptide during secretion process from cell into culture
      supernatant. CONCLUSION: These results suggested that it may be feasible to use
      BEVS system as a high efficient biologic reactor for producing recombinant hBD-2.

PMID- 15573768
TI  - [Inhibitory effect of quercetin, rutin and puerarin on HDL oxidation induced by
      Cu2+].
AB  - OBJECTIVE: To evaluate the inhibitory effect of quercetin, rutin and puerarin on
      the HDL oxidation induced by Cu2+ and to investigate their action on the
      prevention and cure of atherosclerosis. METHODS: The serum HDL of healthy human
      was isolated by the one step density gradient ultracentrifugation. The HDL
      oxidation was induced by Cu2+ in vitro for different time, quercetin and rutin at
      5 micromol/L were added ahead, respectively. HDL was oxidized, then identified by
      A234, REM, TBARS and protein carbonyls content, and was compared with control
      group. Inhibition of puerarin was weak. RESULTS: (1) A234, REM, TBARS and protein
      carbonyls formation increased gradually during HDL oxidation induced by Cu2+ in
      vitro. (2) During HDL oxidation induced by Cu2+ in vitro and incubation with
      quercetin and rutin, the kinetic changes of A234, REM, TBARS and protein
      carbonyls formation showed lag phases of 2 h, 2-4 h, 2-4 h and 4 h respectively,
      and showed reductions by 24.2%-49.0% (P<0.001) and 9.4%-42.0% (P<0.01); 3.0%
      25.0% and 4.0%-20.7% (P<0.05); 7.9%-34.1% and 1.2%-26.8% (P<0.05); 28.3%-50.4%
      and 18.6%-64.6% (P<0.001) respectively. In the puerarin group, only protein
      carbonyls formation showed a lag phase of 4 h and a reduction by 14.1%-52.1%
      (P<0.001) while its A234, REM, TBARS reduced to a small extent. CONCLUSION: The
      above findings suggested that quercetin and rutin inhibit oxidation of HDL
      significantly, but puerarin has less antioxidative function.

PMID- 15573769
TI  - [Study on acute pancreatitis-associated lung injury induced by L-arginine in
      mice].
AB  - OBJECTIVE: To establish the model of acute pancreatitis (AP)-associated lung
      injury induced by L-arginine and study the role of TNF-alpha and ICAM-1 in the
      model mice. METHODS: For the establishment of the AP model, the mice were given
      the first injection (2 g/kg) of L-arginine intraperitoneally and then the second
      injection in the same way an hour later. At 12 h after the second injection, the
      animals' serum amylase activities were assayed by colorimetry, and the tumor
      necrosis factor-alpha (TNF-alpha) contents of their pancreatic tissue were
      determined by radioimmunoassay. At 24 h after the second injection, the
      histopathological changes in the animals' pancreatic and pulmonary tissues were
      observed. The pulmonary expression and cellular localization of intercellular
      adhesion molecule-1 (ICAM-1) were characterized by immunohistochemistry. RESULTS:
      The serum amylase activities, TNF-alpha content and ICAM-1 expression in lung
      tissue significantly increased in the AP group as compared with those in the
      control group. Histopathological examinations revealed that the acinar
      architecture was partially destroyed with necrosis, interstitial edema and
      inflammatory infiltration at 24 h after the second injection. CONCLUSION: TNF
      alpha and ICAM-1 may play important roles in the mice with acute pancreatitis
      associated lung injury.

PMID- 15573770
TI  - [Association between the expression of estrogen receptor subunit in endometrial
      carcinoma and the prognostic factors of endometrial carcinoma].
AB  - OBJECTIVE: To study the relationship between the expression of ERalpha and ERbeta
      mRNA in the fresh tissue from patients with endometrial carcinoma and to evaluate
      the association between the ratio of ERalpha/ERbeta and the prognostic factors of
      endometrial carcinoma. METHODS: Multiplex RT-PCR was used to study the expression
      of ERalpha and ERbeta mRNA in the fresh endometrial tissue from 41 cases of
      endometrial carcinoma. The association between the expression of ERalpha/ERbeta
      mRNA and the prognostic factors of endometrial carcinoma was evaluated. RESULTS:
      ERalpha mRNA and ERbeta mRNA were detected in 95% and 90.2% of the 41 cases of
      endometrial carcinoma, respectively. ERalpha/ERbeta > 1 was detected in 21 cases
      and ERalpha/ERbeta < 1 was detected in 14 cases. Analysis revealed an association
      between the ratio of ERalpha/ERbeta mRNA and the prognostic factors of
      endometrial carcinoma. CONCLUSION: In this study, ERalpha mRNA overexpression
      (ERalpha/ERbeta > 1) was found associated with good prognostic factors of
      endometrial carcinoma, whereas ERbeta mRNA overexpression (ERalpha/ERbeta < 1)
      was found associated with poor prognostic factors of endometrial carcinoma.

PMID- 15573771
TI  - [Relationship between the reduction of FHIT expression and the development of
      cervical carcinoma].
AB  - OBJECTIVE: To explore the relationship between reduction of FHIT expression of
      fragile histidine triad (FHIT) and the development of cervical carcinoma.
      METHODS: Expression of the FHIT product was detected by immunohistochemistry in
      22 normal cervices and 35 cervical intra-epithelial neoplasias (CINs) as well as
      60 primary invasive cervical carcinomas. RESULTS: The rates for loss or reduction
      of expression of FHIT protein in the squamous epithelium of normal cervices, CIN
      I-II, CIN III and noninvasive carcinoma and invasive cervical carcinoma were 0%
      (0/22), 20% (4/20), 53.3% (8/15), 81.7% (49/60) respectively (P<0.05). Among the
      well differentiated, intermediately differentiated and poorly differentiated
      invasive cervical carcinoma, the rates for loss or reduction of expression of
      FHIT protein were 60.0% (6/10), 70.0% (14/20), and 96.7% (29/30) respectively
      (P<0.05). The rate of the impaired FHIT protein expression in the invasive
      cervical carcinoma with lymph node metastasis (90.9%) was higher than that
      without lymph node metastasis (79.6%). CONCLUSION: The impaired FHIT protein
      expression might be a useful indicator in identifying the possibility of the
      progression of advanced CINs into invasive cervical carcinoma. FHIT protein
      expression might indicate the clinical characteristic of cervical carcinoma cells
      and the prognosis of cervical carcinoma.

PMID- 15573772
TI  - [Interobserver reproducibility in the pathologic diagnosis of borderline ductal
      proliferative breast diseases].
AB  - OBJECTIVE: The aim of this study involving general pathologists was to assess
      interobserver reproducibility in the pathologic diagnosis of borderline ductal
      proliferative breast diseases. METHODS: Ten general pathologists independently
      reviewed 43 specimens chosen to represent the spectrum of borderline ductal
      proliferative breast lesions. All slides were blindly reviewed without given
      standardized criteria, and were classified as either mild usual hyperplasia,
      moderate-severe usual hyperplasia, mild atypical hyperplasia, moderate-severe
      atypical hyperplasia, ductal carcinoma in situ, or ductal carcinoma in situ with
      invasion. According to the years of training, these 10 general pathologists were
      divided into the experienced group and the less trained group. Interobserver
      agreement was statistically analyzed using Kappa statistic. Then, by comparing
      all the diagnoses of individual pathologist with the consensus opinion confirmed
      by two breast pathologists in terms of Page standard, we acquired the diagnostic
      accuracy and ascertained the undue diagnosis. RESULTS: The ten general
      pathologists' interobserver reproducibility in the diagnosis of borderline ductal
      proliferative breast diseases was rather low, especially that in their diagnosis
      of atypical hyperplasia. The reproducibility and accuracy were slightly higher in
      the experienced pathologists than in the less trained pathologists. Some
      pathologists made over-diagnosis or under-diagnosis of the lesions to different
      degrees. However, when the categories of diagnostic terms were simplified, the
      interobserver reproducibility increased. CONCLUSION: The use of standardized
      criteria is an important approach to increasing the diagnostic reproducibility
      and accuracy.

PMID- 15573773
TI  - [Preliminary study of the effects of high-dose Vitamin C on acute spinal cord
      injury in rats].
AB  - OBJECTIVE: To investigate the therapeutic effect of high-dose Vitamin C on acute
      spinal cord injury (SCI) in rats. METHODS: Forty-eight SD rats were randomly
      divided into 3 groups (A, B, C), and SCI was made by Allen's Mode (7 g x 4 cm) on
      spinal cord T11 extradurally. Half an hour after SCI, the rats of groups A and B
      were given methylprednosolone (30 mg/kg, i.p.) and Vitamin C (200 mg/kg, i.p.)
      respectively. The rats of Group C recevied normal saline i.p. only. The results
      of hematoxylin staining+Olsiwski corpuscle staining and the moisture of spinal
      cord 48 h after SCI were observed. Inclined plate and Gale scale were observed 2
      weeks after SCI. RESULTS: In both group A and group B, there was less scope of
      neuro-necrosis and bleeding, less degree of hydrops and more Olsiwski corpuscle
      count in neure of injured areas 48 h after injury, and much better behavioral
      assessment (inclined plate+Gale scale) 2 weeks after injury in comparison with
      those in group C (P<0.05), while there were no diffferences between group A and
      group B statistically (P>0.05). CONCLUSION: Early administration of high-dose
      Vitamin C is effective for treating SCI, but its effectiveness is not superior to
      that of high-dose methylprednisolone.

PMID- 15573774
TI  - [Applying competitive polymerase chain reaction to the detection of hepatitis B
      virus DNA].
AB  - OBJECTIVE: To reduce the rate of accidental false negative result in the HBV DNA
      PCR test on clinical serum samples. METHODS: A competitive polymerase chain
      reaction (C-PCR) was used to decrease the false negative ratio. In the C-PCR, a
      constructed inner control DNA was added for co-amplification with the HBV target
      DNA. RESULTS: In a 20 microl C-PCR system, about 60 to 200 copies of inner
      control DNA could give apparent co-amplification signal band after
      electrophoresis on a 2% agarose gel. Five of 120 samples of clinical serum (4.2%)
      could not be amplified. CONCLUSION: C-PCR has the advantage of yielding
      information on false negative in the HBV DNA PCR assay of clinical serum samples.

PMID- 15573775
TI  - [Three-dimensional finite element stress distribution and displacement analysis
      of alveolar ridge retained by conical telescope].
AB  - OBJECTIVE: To study the stress distribution and displacement of edentulous
      alveolar ridge of removable partial denture which is retained by using conical
      telescope. METHODS: An ideal three dimensional finite element model was
      constructed by using SCT image reconstruction technique, self-programming and
      ANSYS software. The static load was applied. The stress and displacement
      characteristics of these different types of materials which form the metal part
      of the conical telescope were compared and analyzed. RESULTS: Generally, the four
      materials produced almost the same stress and displacement at the site of the
      edentulous alveolar ridge. CONCLUSION: From the viewpoint of dynamics, the
      application of different materials in making the metal part of conical telescope
      is feasible.

PMID- 15573776
TI  - [Improvement of the model of pancreas-duodenal transplantation in swines].
AB  - OBJECTIVE: To improve the procedures of pancreas-duodenal transplantation in
      swines in order to establish a technically stable model that accords with the
      physiological situation. METHODS: The whole pancreatoduodenal graft was harvested
      with in situ flush using 4 degrees C preservation solution. Type 1 diabetes was
      induced surgically by total pancreatectomy. By end-to-side fashion, the segment
      of abdominal aorta containing the celiac artery and the anterior mesenteric
      artery (equal to superior mesenteric artery in human) was anastomosed to the
      abdominal aorta of recipient which is behind the renal artery, the portal vein
      was anastomosed to the anterior mesenteric vein of the recipient, the duodenum
      was anastomosed to the jejunum of the recipient. The graft was placed in the
      anterior right peritoneal cavity. RESULTS: A total of 28 swines were used as
      recipients. Of them, two died of anesthetic accident, another two died of
      hyperacute rejection 2 hours, 19 hours after operation respectively; the others
      underwent the operation uneventfully. Their survival time was 5-21 days, blood
      sugar was (11.33+/-1.66) mmol/L on the first day after operation, and (5.65+/
      0.89) mmol/L on the third day. CONCLUSION: This kind of model is stable, and the
      operative method and procedures are relatively simple and practicable.

PMID- 15573777
TI  - [Endoscopic, pathologic-anatomic and histologic findings in the bovine teat. 2.
      Changes in the area of Furstenberg's rosette].
AB  - In the present study endoscopically diagnosed changes of the Furstenberg's
      rosette were examined histologically. For this purpose the teats of 200
      slaughtered cows were inspected. In 19 cases proliferations in the region of the
      Furstenberg's rosette were found. Additionally, tissue samples were taken from
      the Furstenberg's rosette of 26 cows which showed milk flow disorders due to
      stenoses of this part of the teat. Teats of slaughtered cows as well as biopsy
      specimens were fixed in 5% formaldehyde and embedded in paraffin and in plastic.
      All specimens were stained according to H.E., Giemsa and Turnbull, respectively.
      Histologically, the proliferations of the Furstenberg's rosette consisted of
      fibrovascular tissue (granulation tissue) covered by keratinized squamous
      epithelium (teat canal epithelium) in eleven cases. In the other cases double
      layered cuboid epithelium (cisternal epithelium) was found additionally. The
      formation of granulation tissue and deposition of blood pigment was observed
      exclusively in areas covered by stratified epithelium. Therefore a traumatic
      lesion of the teat canal was supposed to be the cause of the histological
      findings. In contrast to several reports in the literature, however, no
      indications of an inversion of the teat canal epithelium were found. On the basis
      of these findings, the hitherto assumed idea of pathogenesis of proliferations of
      the Furstenberg's rosette was modified and a new pathogenesis pattern was
      developed.

PMID- 15573778
TI  - [Use of FAMACHA Scoring System as a diagnostic aid for the registration of
      distinguishing marks in the breeding program for lambs exposed to an experimental
      Haemonchus contortus infection].
AB  - The control of gastro-intestinal nematodes in sheep has almost entirely been
      based on the use of anthelmintics and pasture management. Therefore anthelmintic
      resistance escalated in the past. One way of reducing this problem may be the
      limitation of anthelmintic treatment to those animals with clinical symptoms
      only. The FAMACHA Eye-colour-chart is based on the principle knowledge that the
      colour of mucous membranes are correlated with the anaemiae situation of an
      animal. To monitor anaemic animals they are identified and classified in a 1 to 5
      color scale based on the colour of the conjunctiva, and anaemic animals can be
      selectively treated. It helps to reduce treatments and therefore the development
      of drug resistance. The objective of this study was to estimate the correlation
      between FAMACHA-scores, haematocrit values, faecal egg counts, plasma albumin
      level and worm burden following an experimental infection with Haemonchus
      contortus in lambs. The estimated correlations have been low. This proofs the
      limits of the FAMACHA system under a situation of low parasite pressure.

PMID- 15573779
TI  - [CliniTox: the computer-based information system for poisoning in farm animals].
AB  - Poisonings can cause reduced performance and severe economic loss in farm
      animals. A swift and targeted action is required from veterinarians. We have
      established a computer-based decision support system for poisonings in ruminants
      and pigs. The system offers access to the most recent information available in
      clinical toxicology of farm animals. Towards this goal, relevant reports from the
      peer-reviewed literature were evaluated and organised according to the
      requirements of a structured database. The information provided for each toxic
      substance includes a summary of its chemical and physical properties, sources,
      commercial uses or natural occurrences, toxicokinetic data, mechanisms of action,
      threshold doses, clinical symptoms with brief case reports, sampling and
      analytical results, post-mortem abnormalities, differential diagnoses,
      therapeutic guidelines and references to the literature. This decision support
      system has been programmed with two user-friendly search functions: a search tool
      that allows the choice of clinical and pathological findings, and another
      function that serves to find a substance using its chemical name, the class of
      compounds to wich it belongs, a possible source or one of its main applications.
      CliniTox can be accessed directly via our webserver (http://www.clinitox.ch).

PMID- 15573780
TI  - [Case report. Restrictive cardiomyopathy with chylothorax in a cat: the
      pathogenesis].
AB  - A 8.5 year old castrated female domestic short-haired cat was presented because
      of progressive dyspnea, inappetence and weight loss. Special examinations
      revealed a chylothorax. In addition a restrictive cardiomyopathy was suspected.
      The cat was euthanized. The histopathologic examination of the heart confirmed
      the diagnosis of restrictive cardiomyopathy. The examination of the ductus
      thoracicus showed a intramural fibrosis with additional edema and a interstitial
      partly perivascular inflammation. The coherence between feline cardiopathy and
      chylothorax was discussed speculatively in previous reports. In this report we
      show a possible aetiopathology.

PMID- 15573781
TI  - [Case-report. Malignant nerve sheath tumor in a cow with symptoms of suspected
      BSE].
AB  - We report here on a 3 1/2-year-old mother cow with a malignant perineural tumour
      near the pontine angle of the cerebellum, but which first drew attention because
      of clinical signs of BSE. Neurological symptoms that manifested during the course
      of the disease included disturbances in behaviour, movement and aesthesia, as
      described by BRAUN et al. (2001) in cases of BSE. Inconsistent with a diagnosis
      of BSE were focal neurological disturbances (head held aslant to the right,
      tendency to fall to the right, right-sided facial weakness, left-sided nystagmus
      and ventral strabismus). Following euthanasia, magnetic resonance imaging (MRI)
      revealed a tumour in the cerebellopontine angle. Histological findings describe a
      malignant peripheral nerve tumour of the vagal nerve with rhabdoid
      differentiation (a so-called Triton tumour) with an intracranial and an
      extracranial part.

PMID- 15573782
TI  - International disease surveillance. International disease monitoring, July to
      September 2004.

PMID- 15573783
TI  - Liverpool Veterinary School: the first 100 years.
AB  - In 1904, Liverpool veterinary school became the first UK veterinary school to be
      incorporated into a university. This weekend, it marks its centenary with a
      symposium celebrating veterinary science and its contribution to animal and human
      health and welfare. Here, Alison Kraft traces the history of the school and
      argues that its foundation was a turning point for veterinary education in the
      UK.

PMID- 15573784
TI  - Prevalence and demographic characteristics of exertional rhabdomyolysis in horses
      in Australia.
AB  - The proportion of the horses, of both sexes and of different ages, breeds and
      levels of activity, owned by a stratified random sample of Australian owners,
      which had suffered one or more episodes of exertional rhabdomyolysis during the
      previous 12 months was determined. The proportion in the general population was
      1.9 per cent, and horses which exercised were significantly more likely to have
      experienced the condition than horses which did not. There were significant
      differences between the sexes and between certain breeds and activity groups in
      the proportions of horses affected.

PMID- 15573785
TI  - Measurement of the thickness of the corium and subcutaneous tissue of the hind
      claws of dairy cattle by ultrasound.
AB  - The thickness of the subsolar soft tissue layer (dermis and subcutaneous tissue)
      of the hind lateral and medial claws of 23 Holstein dairy cattle was measured by
      ultrasound imaging. The results showed that on average the subsolar soft tissue
      layer of the lateral hind claw was significantly thicker (4.29 mm) than that of
      the medial hind claw (3.92 mm).

PMID- 15573786
TI  - Effects of a synthetic progestogen, altrenogest, on oestrus synchronisation and
      fertility in miniature pigs.
AB  - Groups of six, six and eight miniature gilts, respectively, received 5, 10 or 15
      mg/day of altrenogest for 18 days, and the numbers of corpora lutea and residual
      follicles were counted approximately 14 days after the treatment by an
      exploratory laparotomy. They were compared with the numbers in a control group of
      eight gilts which were examined six to eight days after oestrus. The interval
      between the last dose of altrenogest and the onset of oestrus increased with the
      dose of altrenogest, and was significantly longer after the treatments with 10 or
      15 mg/day than after 5 mg/day (P < 0.01). Significantly more corpora lutea were
      observed in the gilts receiving 5 or 10 mg/day of altrenogest than in the control
      gilts (P < 0.1). Groups of six, seven and six miniature gilts that had
      respectively received 5, 10 or 15 mg/day of altrenogest were artificially
      inseminated; four, six and five of the gilts in these groups farrowed, and their
      mean (sd) litter sizes were 5.5 (2.4), 6.8 (1.2) and 5.0 (2.3), respectively. All
      six of a group of control gilts farrowed and their mean litter size was 5.8
      (1.2).

PMID- 15573787
TI  - Two Irish cases of scrapie resembling Nor98.

PMID- 15573788
TI  - Adult Dirofilaria repens nematodes in a cat from Kiev, Ukraine.

PMID- 15573789
TI  - Indirect ELISA for the detection of antibodies to Brucella melitensis in sheep
      milk.

PMID- 15573790
TI  - Iridociliary epithelial adenoma in a sheep.

PMID- 15573791
TI  - Standards for international trade.

PMID- 15573792
TI  - Determining bone damage in laying hens.

PMID- 15573793
TI  - FMD and the contiguous cull.

PMID- 15573794
TI  - FMD and the contiguous cull.

PMID- 15573795
TI  - Coccidiosis associated with Eimeria species in gilts.

PMID- 15573796
TI  - Testing for equine arteritis virus.

PMID- 15573797
TI  - Permethrin toxicity in cats.

PMID- 15573798
TI  - Early neutering of cats.

PMID- 15573799
TI  - Vasectomising stray dogs.

PMID- 15573800
TI  - A process to address disparities in rates of sudden infant death syndrome.
AB  - Fetal and Infant Mortality Review (FIMR) is a continuous quality improvement
      program that leads to improvements in services and resources for families and,
      ultimately, a decrease in infant mortality. It is an action-oriented process that
      combines medical data with the mother's report of experiences during the life and
      death of her infant. The FIMR has proven to be especially important in addressing
      community issues associated with infant deaths related to sudden infant death
      syndrome.

PMID- 15573801
TI  - Lessons learned after the withdrawal of rofecoxib.

PMID- 15573802
TI  - Formulary decision-making considerations: COX-2 inhibitors.
AB  - When deciding the formulary status of a drug, Pharmacy & Therapeutics Committees
      must consider clinical efficacy, safety, financial implications, MCO population
      demographics, and other formulary options currently available. Differences in
      safety and effectiveness among drug classes and among drugs in the same class
      commonly take precedence over all other considerations, including economic ones.
      Particularly in light of recent events, the case of the cyclooxygenase-2
      inhibitors for the treatment of arthritis yields interesting perspectives into
      formulary decision making.

PMID- 15573803
TI  - Problems with finding evidence for rare events.

PMID- 15573804
TI  - The implications of poor medication persistence with treatment for overactive
      bladder.
AB  - Overactive bladder (OAB) affects more than 17 million Americans and accounts for
      more than dollar 12 billion annually in health care costs. To stem the costs of
      this disease and increase treatment effectiveness, pharmacological therapies must
      be taken as prescribed over time. Greater persistence with medication can improve
      clinical, economic, and humanistic outcomes in OAB. Therapeutic regimens must be
      effective and well tolerated by patients to create greater persistence and to
      help reduce health care costs among patients with OAB.

PMID- 15573805
TI  - The United Kingdom tries pay for performance.

PMID- 15573806
TI  - A call to action on technology.

PMID- 15573807
TI  - Quality: a work in progress.

PMID- 15573808
TI  - Achieving quality first. The keys to achieving quality are culture change,
      benchmarking data, and risk managment.

PMID- 15573809
TI  - Walking the evidence-based path. From data collection to final evaluation, the
      path to continuous quality improvement is a step-by-step process.

PMID- 15573810
TI  - Managing risk proactively. To break the litigation cycle, providers must
      demonstrate that they can react before problems occur.

PMID- 15573811
TI  - Measuring and benchmarking data. Meeting regulatory goals remains important, but
      it is no longer a sufficient test of quality performance.

PMID- 15573812
TI  - Florida facilities down but not out.

PMID- 15573813
TI  - Keeping hypertension in check.

PMID- 15573814
TI  - SNF consolidated billing revisited.

PMID- 15573815
TI  - A looks at self-insurance trusts.

PMID- 15573816
TI  - Shape-based recognition of wiry objects.
AB  - We present an approach to the recognition of complex-shaped objects in cluttered
      environments based on edge information. We first use example images of a target
      object in typical environments to train a classifier cascade that determines
      whether edge pixels in an image belong to an instance of the desired object or
      the clutter. Presented with a novel image, we use the cascade to discard clutter
      edge pixels and group the object edge pixels into overall detections of the
      object. The features used for the edge pixel classification are localized, sparse
      edge density operations. Experiments validate the effectiveness of the technique
      for recognition of a set of complex objects in a variety of cluttered indoor
      scenes under arbitrary out-of-image-plane rotation. Furthermore, our experiments
      suggest that the technique is robust to variations between training and testing
      environments and is efficient at runtime.

PMID- 15573817
TI  - Semisupervised learning of classifiers: theory, algorithms, and their application
      to human-computer interaction.
AB  - Automatic classification is one of the basic tasks required in any pattern
      recognition and human computer interaction application. In this paper, we discuss
      training probabilistic classifiers with labeled and unlabeled data. We provide a
      new analysis that shows under what conditions unlabeled data can be used in
      learning to improve classification performance. We also show that, if the
      conditions are violated, using unlabeled data can be detrimental to
      classification performance. We discuss the implications of this analysis to a
      specific type of probabilistic classifiers, Bayesian networks, and propose a new
      structure learning algorithm that can utilize unlabeled data to improve
      classification. Finally, we show how the resulting algorithms are successfully
      employed in two applications related to human-computer interaction and pattern
      recognition: facial expression recognition and face detection.

PMID- 15573818
TI  - Frequency domain formulation of active parametric deformable models.
AB  - Active deformable models are simple tools, very popular in computer vision and
      computer graphics, for solving ill-posed problems or mimic real physical systems.
      The classical formulation is given in the spatial domain, the motor of the
      procedure is a second-order linear system, and rigidity and elasticity are the
      basic parameters for its characterization. This paper proposes a novel
      formulation based on a frequency-domain analysis: The internal energy functional
      and the Lagrange minimization are performed entirely in the frequency domain,
      which leads to a simple formulation and design. The frequency-based
      implementation offers important computational savings in comparison to the
      original one, a feature that is improved by the efficient hardware and software
      computation of the FFT algorithm. This new formulation focuses on the stiffness
      spectrum, allowing the possibility of constructing deformable models apart from
      the elasticity and rigidity-based original formulation. Simulation examples
      validate the theoretical results.

PMID- 15573819
TI  - Detection of image structures using the Fisher information and the Rao metric.
AB  - In many detection problems, the structures to be detected are parameterized by
      the points of a parameter space. If the conditional probability density function
      for the measurements is known, then detection can be achieved by sampling the
      parameter space at a finite number of points and checking each point to see if
      the corresponding structure is supported by the data. The number of samples and
      the distances between neighboring samples are calculated using the Rao metric on
      the parameter space. The Rao metric is obtained from the Fisher information which
      is, in turn, obtained from the conditional probability density function. An upper
      bound is obtained for the probability of a false detection. The calculations are
      simplified in the low noise case by making an asymptotic approximation to the
      Fisher information. An application to line detection is described. Expressions
      are obtained for the asymptotic approximation to the Fisher information, the
      volume of the parameter space, and the number of samples. The time complexity for
      line detection is estimated. An experimental comparison is made with a Hough
      transform-based method for detecting lines.

PMID- 15573820
TI  - Recognition by symmetry derivatives and the generalized structure tensor.
AB  - We suggest a set of complex differential operators that can be used to produce
      and filter dense orientation (tensor) fields for feature extraction, matching,
      and pattern recognition. We present results on the invariance properties of these
      operators, that we call symmetry derivatives. These show that, in contrast to
      ordinary derivatives, all orders of symmetry derivatives of Gaussians yield a
      remarkable invariance: They are obtained by replacing the original differential
      polynomial with the same polynomial, but using ordinary coordinates x and y
      corresponding to partial derivatives. Moreover, the symmetry derivatives of
      Gaussians are closed under the convolution operator and they are invariant to the
      Fourier transform. The equivalent of the structure tensor, representing and
      extracting orientations of curve patterns, had previously been shown to hold in
      harmonic coordinates in a nearly identical manner. As a result, positions,
      orientations, and certainties of intricate patterns, e.g., spirals, crosses,
      parabolic shapes, can be modeled by use of symmetry derivatives of Gaussians with
      greater analytical precision as well as computational efficiency. Since Gaussians
      and their derivatives are utilized extensively in image processing, the revealed
      properties have practical consequences for local orientation based feature
      extraction. The usefulness of these results is demonstrated by two applications:
      1) tracking cross markers in long image sequences from vehicle crash tests and 2)
      alignment of noisy fingerprints.

PMID- 15573821
TI  - A coarse-to-fine strategy for multiclass shape detection.
AB  - Multiclass shape detection, in the sense of recognizing and localizing instances
      from multiple shape classes, is formulated as a two-step process in which local
      indexing primes global interpretation. During indexing a list of instantiations
      (shape identities and poses) is compiled, constrained only by no missed
      detections at the expense of false positives. Global information, such as
      expected relationships among poses, is incorporated afterward to remove
      ambiguities. This division is motivated by computational efficiency. In addition,
      indexing itself is organized as a coarse-to-fine search simultaneously in class
      and pose. This search can be interpreted as successive approximations to
      likelihood ratio tests arising from a simple ("naive Bayes") statistical model
      for the edge maps extracted from the original images. The key to constructing
      efficient "hypothesis tests" for multiple classes and poses is local ORing; in
      particular, spread edges provide imprecise but common and locally invariant
      features. Natural tradeoffs then emerge between discrimination and the pattern of
      spreading. These are analyzed mathematically within the model-based framework and
      the whole procedure is illustrated by experiments in reading license plates.

PMID- 15573822
TI  - The visual hull of smooth curved objects.
AB  - The visual hull is a geometric entity that relates the shape of an object to its
      silhouettes or shadows. This paper develops the theory of the visual hull of
      generic smooth objects. We show that the visual hull can be constructed using
      surfaces which partition the viewpoint space of the aspect graph of the object.
      The surfaces are those generated by the visual events tangent crossing and triple
      point. An analysis based on the shape of the object at the tangency points of
      these surfaces allows pruning away many surfaces and patches not relevant to the
      construction. An algorithm for computing the visual hull is outlined.

PMID- 15573823
TI  - Globally convergent autocalibration using interval analysis.
AB  - We address the problem of autocalibration of a moving camera with unknown
      constant intrinsic parameters. Existing autocalibration techniques use numerical
      optimization algorithms whose convergence to the correct result cannot be
      guaranteed, in general. To address this problem, we have developed a method where
      an interval branch-and-bound method is employed for numerical minimization.
      Thanks to the properties of Interval Analysis this method converges to the global
      solution with mathematical certainty and arbitrary accuracy and the only input
      information it requires from the user are a set of point correspondences and a
      search interval. The cost function is based on the Huang-Faugeras constraint of
      the essential matrix. A recently proposed interval extension based on Bernstein
      polynomial forms has been investigated to speed up the search for the solution.
      Finally, experimental results are presented.

PMID- 15573824
TI  - Correlation filter: an accurate approach to detect and locate low contrast
      character strings in complex table environment.
AB  - Correlation has been used extensively in object detection field. In this paper,
      two kinds of correlation filters, Minimum Average Correlation Energy (MACE) and
      Extended Maximum Average Correlation Height (EMACH), are applied as adaptive
      shift locators to detect and locate smudgy character strings in complex tabular
      color flight coupon images. These strings in irregular tabular coupon are
      computer-printed characters but of low contrast and could be shifted out of the
      table so that we cannot detect and locate them using traditional algorithms. In
      our experiment, strings are extracted in the preprocessing phase by removing
      background and then based on geometric information, two correlation filters are
      applied to locate expected fields. We compare results from two correlation
      filters and demonstrate that this algorithm is a high accurate approach.

PMID- 15573825
TI  - Eigenregions for image classification.
AB  - For certain databases and classification tasks, analyzing images based region
      features instead of image features results in more accurate classifications. We
      introduce eigenregions, which are geometrical features that encompass area,
      location, and shape properties of an image region, even if the region is
      spatially incoherent. Eigenregions are calculated using principal component
      analysis (PCA). On a database of 77,000 different regions obtained through the
      segmentation of 13,500 real-scene photographic images taken by nonprofessionals,
      eigenregions improved the detection of localized image classes by a noticeable
      amount. Additionally, eigenregions allow us to prove that the largest variance in
      natural image region geometry is due to its area and not to shape or position.

PMID- 15573826
TI  - Spherical diffusion for 3D surface smoothing.
AB  - A diffusion-based approach to surface smoothing is presented. Surfaces are
      represented as scalar functions defined on the sphere. The approach is equivalent
      to Gaussian smoothing on the sphere and is computationally efficient since it
      does not require iterative smoothing. Furthermore, it does not suffer from the
      well-known shrinkage problem. Evolution of important shape features (parabolic
      curves) under diffusion is demonstrated. A nonlinear modification of the
      diffusion process is introduced in order to improve smoothing behavior of
      elongated and poorly centered objects.

PMID- 15573827
TI  - Education for people with progressive neurological conditions can have negative
      effects: evidence from a randomized controlled trial.
AB  - OBJECTIVES: To test the effects of a home-based educational intervention in
      reducing the incidence and the risk of falls and pressure sores in adults with
      progressive neurological conditions. DESIGN: Randomized controlled trial with 12
      months follow-up. SETTING: Participants' homes in the City of Nottingham.
      PARTICIPANTS: One hundred and fourteen people with progressive neurological
      conditions recruited from general practices in Nottingham, including 53 with
      Parkinson's disease and 45 with multiple sclerosis. INTERVENTIONS: In the
      education group (EG), baseline data were reviewed by an expert panel which
      advised on actions most likely to promote each individual's physical, social and
      psychological well-being. An occupational therapist (OT) then visited EG
      participants to provide education and information and to discuss a personalized
      12-month health action plan. The comparison group (CoG) received standardized
      printed information delivered to their home. MAIN MEASURES: Numbers of
      participants reporting falls and skin sores at two-monthly phone calls during the
      follow-up period of 12 months. RESULTS: The EG reported significantly more falls
      during the follow-up period and at 12 months (adjusted odds ratio 2.83 (95% CI
      1.07-7.47), p=0.036) and significantly more skin sores (adjusted odds ratio 12.74
      (95% CI 1.14-142.6), p =0.039) than the CoG. There was no difference between CoG
      and EG in the Nottingham Extended Activities of Daily Living score, but EG
      patients showed a significant rise in this score over the study period of 1.62
      (95% CI 0.69-2.55, p=0.002). CONCLUSIONS: Our findings provide evidence that
      education for people with progressive neurological conditions can have negative
      effects.

PMID- 15573828
TI  - A randomized trial to evaluate an education programme for patients and carers
      after stroke.
AB  - OBJECTIVES: To evaluate the effectiveness of an education programme for patients
      and carers recovering from stroke. DESIGN: Randomized controlled trial. SUBJECTS
      AND SETTING: One hundred and seventy patients admitted to a stroke rehabilitation
      unit and 97 carers of these patients. INTERVENTIONS: The intervention group
      received a specifically designed stroke information manual and were invited to
      attend education meetings every two weeks with members of their multidisciplinary
      team. The control group received usual practice. MEASURES: Primary outcome was
      knowledge of stroke and stroke services. Secondary outcomes were handicap (London
      Handicap Scale), physical function (Barthel Index), social function (Frenchay
      Activities Index), mood (Hospital Anxiety and Depression Scale) and satisfaction
      (Pound Scale). Carer mood was measured by the General Health Questionnaire-28.
      RESULTS: There was no statistical evidence for a treatment effect on knowledge
      but there were trends that favoured the intervention. The education programme was
      associated with a significantly greater reduction in patient anxiety score at
      both three months (p =0.034) and six months (p =0.021) and consequently fewer
      'cases' (Hospital Anxiety and Depression Scale anxiety subscale score > or =11).
      There were no other significant statistical differences between the patient or
      carer groups for other outcomes, although there were trends in favour of the
      education programme. CONCLUSION: An education programme delivered within a stroke
      unit did not result in improved knowledge about stroke and stroke services but
      there was a significant reduction in patient anxiety at six months post stroke
      onset.

PMID- 15573829
TI  - Effects of aerobic and strength exercise on motor fatigue in men and women with
      multiple sclerosis: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of aerobic and strength exercise on motor
      fatigue of knee flexor and extensor muscles in subjects with multiple sclerosis
      (MS). DESIGN: A randomized controlled trial. SETTING: At Masku Neurological
      Rehabilitation Centre, Masku, and the Social Insurance Institution, Research
      Department, Turku, Finland. SUBJECTS: Ninety-five MS patients with mild to
      moderate disability were randomized into exercise group (n =47) and a control
      group (n =48). INTERVENTION: Participants in the exercise group attended in a
      supervised exercise period of three weeks, which was followed by a home exercise
      programme lasting for 23 weeks. Patients in the control group continued with
      their normal living. OUTCOME MEASURES: Motor fatigue of knee flexor and extensor
      muscles was measured during a static 30-s maximal sustained muscle contraction.
      The decline in force (Nm) during the 30 s was recorded, and a fatigue index (FI)
      was calculated. Subjective fatigue was measured by using the Fatigue Severity
      Scale (FSS). The Ambulatory Fatigue Index (AFI) was calculated on the basis of a
      500-m walking test. Assessment took place at baseline, at the third week (not for
      the control group) and at the 26th week. All outcome variables were analysed, men
      and women together, and some interesting contrasts were analysed by gender.
      RESULTS: Associations were observed with changes in extension FI and Expanded
      Disability Status Scale (EDSS) score and mean extension torque (Nm), but not with
      changes in FI and aerobic or strength exercise activity, mean AFI, mean FSS or in
      mean knee flexion torque. AFI was decreased in all subject groups (p =0.007).
      Motor fatigue was reduced in knee flexion (p=0.0014) and extension (ns) among
      female but not in male exercisers after six months of exercise. The exercise
      activity of women was 25% higher than that of the men. CONCLUSIONS: Six months of
      exercise reduced motor fatigue in women, but not in men.

PMID- 15573830
TI  - Effects of visual feedback rhythmic weight-shift training on hemiplegic stroke
      patients.
AB  - OBJECTIVE: To assess the balance function of hemiplegic stroke patients and to
      investigate whether visual feedback rhythmic weight-shift training following
      acute stroke can decrease falls among patients with hemiplegic stroke. DESIGN: A
      prospective study, using a Balance Master. SETTING: Hospital-based rehabilitation
      units. SUBJECTS: Fifty-two hemiplegic stroke patients (28 in the training group
      and 24 in the control group). INTERVENTIONS: Conventional stroke rehabilitation
      programme plus visual feedback rhythmic weight-shift training. Training effect
      was evaluated by assessing the static and dynamic balance performance as well as
      comparing the occurrence of falls in the training and control groups at six-month
      follow-up. MAIN MEASURES: Occurrence of falls; static balance in different
      sensory conditions; and dynamic balance performance, including on-axis velocity
      and directional control during rhythmic weight-shift. RESULTS: Significant
      improvement in dynamic balance performance was found in hemiplegic patients in
      the training group. The improvement was sustained for six months. With regarding
      to static balance function, no significant improvement was found. At six-month
      follow-up, 5 of 28 patients (17.8%) in the training group had fallen, compared
      with 10 of 24 patients (41.7%) in the control group. The occurrence of falls
      decreased, although not statistically significantly (p=0.059). CONCLUSIONS:
      Visual feedback rhythmic weight-shift training may improve dynamic balance
      function for hemiplegic stroke patients. The effects of training may be sustained
      for six months. The occurrence of falls decreased in the training group, but not
      statistically significantly.

PMID- 15573831
TI  - A multiple case design experiment to investigate the performance and neural
      effects of a programme for training hand function after stroke.
AB  - OBJECTIVE: To investigate the effects of task-specific practice on hand function
      in stroke subjects who were given computer-assisted training and to look for
      associated changes in corticospinal connectivity. DESIGN: Single case design
      experiments. SETTING: Subjects' homes. SUBJECTS: Seven chronic stroke subjects
      with impaired hand function. INTERVENTIONS: Daily intensive practice of fast and
      accurate force changes in pinch grip and knob turning grip for four weeks. MAIN
      MEASURES: Pinch and power grip strength and dexterity measured using the Ten-hole
      Peg Test and a timed nuts and bolts test were recorded twice a week throughout
      the study. Corticospinal connectivity was assessed by latency of electromyography
      (EMG) responses to transcranial magnetic stimulation (TMS) recorded during the
      baseline weeks before the training and again immediately after the training
      period. RESULTS: Subjects completed between 5760 and 18560 force changes.
      Clinically relevant improvements in grip strength were evident in only two
      subjects. None of the subjects showed clinically significant improvement in
      dexterity measures. Statistical analysis showed that improved performance was
      related to the training phase in only two subjects. A reduction in latency of EMG
      responses to TMS was seen in two subjects but could not be attributed to the
      training phase. CONCLUSIONS: The intensive training did not improve hand function
      in most subjects. Latencies of EMG responses to TMS were also unable to detect
      any change.

PMID- 15573832
TI  - Treatment of recurrent posterior dislocation of the shoulder in cerebral palsy by
      injection with botulinum toxin A into the M. subscapularis.
AB  - SUBJECTS: A 20-year-old woman, known to have cerebral palsy and a spastic
      hemiparesis, suffered from frequent (up to 20 times a day) and painful posterior
      dislocation of the affected shoulder. INTERVENTIONS: For the last two years we
      have treated her with injections with botulinum toxin A (100 U Botox) in the M.
      subscapularis. RESULTS: Pain and dislocation rate have improved substantially.

PMID- 15573833
TI  - Beyond restoration to transformation: positive outcomes in the rehabilitation of
      acquired brain injury.
AB  - OBJECTIVES: This paper compares the situation of the person with acquired brain
      injury to that of the people of Israel in the sixth century BCE (before the
      current era) during the period of exile in Babylon. Both situations are
      characterized by traumatic multiple losses, and a struggle to regain a sense of
      identity: personal, national or spiritual. Evidence from the literature on both
      brain injury rehabilitation and from the Hebrew Scriptures indicates that models
      of restoration of function and transformation of suffering have been applied to
      both situations. The relative strengths and weaknesses of these models are
      considered, and it is argued that models of transformation of suffering have much
      to offer, especially in the longer term psychotherapeutic rehabilitation of
      people with acquired brain injury, when restoration of function has reached its
      limits.

PMID- 15573834
TI  - An exploration looking at the impact of domiciliary and day hospital delivery of
      stroke rehabilitation on informal carers.
AB  - OBJECTIVES: To explore the impact of two methods of post-hospital stroke
      rehabilitation on both carers' perceptions of the health services offered and
      their quality of life. SETTING: East Dorset Health Authority. SUBJECTS: Forty-six
      informal carers were recruited from a sample of 106, initially identified from
      stroke patients participating in a larger randomized controlled trial. DESIGN:
      Qualitative methods. METHODS: Semi-structured interviews were used at baseline
      and six months to explore carers' perception of a good therapy, the advantages
      and disadvantages of the different services and their fulfilment with the
      services. In-depth thematic analysis was carried out to explore the impact of the
      two different methods of service delivery on carers' quality of life. RESULTS:
      Day hospitals provided carers with respite opportunities, whilst domiciliary
      stroke teams provided carers with better educational opportunities to be involved
      in therapy. No qualitative difference was found in the impact that the different
      services had on carers' quality of life, which were influenced by factors such as
      the degree of disruption that caring had on their lives, the loss of a shared
      life and the availability of social support. Ultimately, carers saw the services
      as providing benefit for survivors and not themselves. CONCLUSIONS: Domiciliary
      stroke teams provided informal stroke carers with skills that could help improve
      postdischarge stroke rehabilitation amongst stroke survivors. Informal carers
      also benefited from the respite elements of day hospital. A mixed model using
      both domiciliary care and day hospital care, could provide carers with the
      benefits of education, convenience and respite.

PMID- 15573835
TI  - Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for
      chronic fatigue syndrome.
AB  - PURPOSE: To establish an inexpensive, simple method of predicting peak oxygen
      uptake (VO2peak) in patients fulfilling the 1994 Centers for Disease Control and
      Prevention (CDC) criteria for chronic fatigue syndrome (CFS). DESIGN: A
      retrospective observational study. SETTING: An outpatient tertiary care chronic
      fatigue clinic. SUBJECTS: Two hundred and forty consecutive patients fulfilling
      the 1994 CDC criteria for CFS. INTERVENTIONS: Heart rate, metabolic and
      ventilatory parameters were measured continuously during a maximal exercise
      stress test on a bicycle ergometer. Using the equation peak oxygen uptake = 13.1
      x peak workload +284 (used by Mullis et al., Br J Sports Med 1999; 33: 352-56),
      VO2peak was predicted from the peak workload of a maximal exercise capacity test.
      Pearson correlation coefficient and linear regression analysis were used to
      establish the most accurate way to predict VO2peak. RESULTS: Percentage error
      encountered when comparing actual measured VO2peak with predicted value was 17.3%
      (+/-10.0). A strong correlation between VO2peak and peak workload was observed
      (r= 0.89, p < 0.001). A regression analysis established the relation as VO2peak =
      10.47 x peak workload +284.1, where VO2peak is given in ml/min and peak workload
      in W (error in prediction = 11.0+/-9.5%). CONCLUSIONS: Monitoring of the peak
      workload during a maximal, graded bicycle ergometric test suffices to predict the
      VO2peak. When predicting VO2peak the used operational definition for the
      diagnosis of CFS could be taken into account. Compared with the equation used by
      Mullis et al., peak workload is multiplied by 10.47 in order to predict peak
      oxygen uptake in CDC-defined CFS patients.

PMID- 15573836
TI  - Association between radiographic joint space narrowing, function, pain and muscle
      power in severe osteoarthritis of the knee.
AB  - OBJECTIVE: To examine the association between radiographic classification of
      severe knee osteoarthritis and measurements of function, pain and power. DESIGN:
      Cross-sectional study. SETTING: Specialist orthopaedic hospital. SUBJECTS: One
      hundred and twenty-three patients on the waiting list for elective knee
      arthroplasty. OUTCOME MEASURES: Weight-bearing antero-posterior radiographs
      scored for severity of osteoarthritis using the Kellgren and Lawrence scale.
      Function measured using the function subscale of the WOMAC (Western Ontario and
      McMaster Universities) index, timed tests of walking speed and sit-to-stand. Pain
      measured using the pain subscale of the WOMAC index and a visual analogue scale.
      Extensor strength of the lower limb measured with the leg extensor power rig.
      RESULTS: Within any radiographic grade there was considerable variation in
      function: WOMAC function for patients with grade 2 mean 64 (47-86), grade 3 mean
      47 (12-89) grade 4 mean 45 (2-92). There was poor correlation between
      radiographic score function, pain or muscle power, with no statistically
      significant associations. A wide range of scores was also seen within patients
      with the same radiographic grade. CONCLUSIONS: Radiographic score was not found
      to be closely associated with function. Amongst patients with the same
      radiographic score there was considerable variation in function, pain and power.

PMID- 15573837
TI  - Development of the Brunel Balance Assessment: a new measure of balance disability
      post stroke.
AB  - OBJECTIVE: To report the psychometric properties of the Brunel Balance Assessment
      (BBA), a new test of balance disability post stroke. DESIGN: Data from 92
      subjects were collected and cohorts used to test hierarchical scaling,
      reliability and validity. Data from 80 people were used to test the hierarchical
      scaling using an inter-item correlation for redundancy, coefficient of
      reproducibility (CR) and scalability (CS) for the hierarchy and Cronbach's alpha
      coefficient for the internal consistency. Thirty-seven people participated in the
      reliability testing. Test-retest and inter-tester reliability were tested using
      the kappa coefficient. The testing was repeated on consecutive days to assess
      test-retest reliability and was scored simultaneously by two physiotherapists for
      inter-tester reliability. Fifty-five people participated in validity testing. The
      BBA was compared with the sitting Motor Assessment Scale (MAS), Berg Balance Test
      (Berg), Rivermead Mobility Index (RMI) using Spearman's rho. SETTING:
      Physiotherapy stroke services of six UK NHS trusts. PARTICIPANTS: Hemiplegic
      stroke patients were recruited from physiotherapy services and the BBA used to
      assess their balance. RESULTS: The order of the items was revised and the
      original 14-point scale reduced to 12 points in the scale development. The
      revised scale formed a hierarchical scale. Inter-item correlations were < 0.9,
      coefficients of reproducibility and scalability were 0.99 and 0.69 respectively
      and Cronbach's alpha was 0.92. Reliability was high (100% agreement) for both
      aspects of reliability. Correlations with other balance measures were significant
      (0.83-0.97, p < 0.01) indicating validity as measure of balance disability.
      CONCLUSION: The BBA is a reliable, valid, hierarchical measure of balance
      disability post stroke that is suitable for use in the clinical setting.

PMID- 15573838
TI  - Berg Balance Scale and Functional Reach: determining the best clinical tool for
      individuals post acute stroke.
AB  - OBJECTIVE: To begin the process of determining the best clinical tool for
      measuring balance in individuals post stroke. DESIGN: Prospective with
      descriptive and relational analyses. SETTING: Rehabilitation centres and stroke
      support group meetings. SUBJECTS: Seventy-five subjects who had suffered a stroke
      were divided into four groups based on the Duncan classification for stroke
      severity. MAIN OUTCOME MEASURES: The motor section of the Fugl-Meyer Assessment
      of Physical Performance was completed for each person to classify the motor
      deficit. Subjects performed Functional Reach twice with the nonparetic arm and
      the average was recorded. Subjects performed the Berg Balance Scale and the total
      score on the first attempt was recorded. RESULTS: As motor impairment increased,
      balance ability declined and both the Functional Reach and Berg Balance Scale
      proved sensitive to this decline. Spearman rank correlation coefficient was
      excellent among the entire sample (r(s) =0.78). CONCLUSION: Subjects' performance
      on the Berg Balance Scale was closely associated with performance on the
      Functional Reach. Therefore, the clinician may elect to use the shorter
      Functional Reach as a measure of balance where efficient use of time is the
      primary goal.

PMID- 15573839
TI  - Assessment of apraxia: inter-rater reliability of a new apraxia test, association
      between apraxia and other cognitive deficits and prevalence of apraxia in a
      rehabilitation setting.
AB  - OBJECTIVE: To investigate the inter-rater reliability of a new apraxia test.
      Furthermore to examine the association of apraxia with other neuropsychological
      impairments and the prevalence of apraxia in a rehabilitation setting on the
      basis of the new test. DESIGN: Cross-sectional cohort study, involving 100
      patients with a first stroke admitted to a rehabilitation centre in the
      Netherlands. MEASURES: General patient characteristics and stroke-related
      aspects. Cognitive screening involving apraxia, visuospatial scanning, abstract
      thinking and reasoning, memory, attention, planning and aphasia. RESULTS: The
      indices for inter-rater agreement range from excellent to poor. Significant
      correlations are found between apraxia and visuospatial scanning, memory,
      attention, planning and aphasia. The patients with apraxia perform significantly
      worse than the patients without apraxia on memory, the time needed to complete
      the tests for scanning and attention, and aphasia. The prevalence of apraxia is
      25.3% in the total group, 51.3% in the left hemisphere stroke patients and 6.0%
      in the right hemisphere stroke patients. Patients with and without apraxia do not
      differ significantly concerning age, gender and type of stroke. CONCLUSION: The
      apraxia test has been shown to be a reliable instrument. Apraxia is often
      associated with aphasia, memory problems and mental slowness. This study shows
      that on the basis of the apraxia test, the prevalence of apraxia among patients
      in the rehabilitation centre is high, especially among patients with left
      hemisphere lesions.

PMID- 15573840
TI  - Prismatic correction in patients affected by age-related macular degeneration.
AB  - OBJECTIVE: To evaluate by means of a controlled clinical trial the effectiveness
      and the tolerance of prismatic correction in improving visual function in
      patients affected by advanced bilateral age-related macular degeneration.
      SETTING: Department of Ophthalmology, Eye Clinic, University of Trieste. SUBJECTS
      AND INTERVENTIONS: Each patient underwent an ophthalmologic examination, complete
      with distance visual acuity measurement using the Standard Early Treatment
      Diabetic Retinopathy Study chart. Patients were then randomly assigned to the
      treatment or control group. The treatment group received spectacles lenses with a
      prismatic correction of low power (5-7 prismatic dioptres) in the better eye.
      MAIN MEASURES: Visual acuity was measured at baseline and 1, 90, 180 and 360 days
      after prescription in both groups. RESULTS: The treatment group consisted of 14
      patients, while the control group was of 14 patients. The prismatic correction
      was well tolerated in 85.7% of cases. Visual acuity in the treatment group
      improved mostly at three-month follow-up, with a slight further improvement at
      the six- and 12-month follow-ups, showing a statistically significant difference
      in comparison with the control group. No visual acuity improvement was registered
      in the control group. CONCLUSION: Monolateral prismatic correction may be
      considered a viable means to improve visual function in patients affected by
      bilateral age-related macular degeneration at an advanced stage.

PMID- 15573841
TI  - Exercise treatment for osteoarthritis disability.
AB  - Osteoarthritis (OA) is a chronic prevalent condition that affects the synovial
      joints and can lead to disability. There is no single treatment that is known to
      cure OA. Most treatments have aimed at reducing symptoms or slowing the
      progression of the disease and its consequences. Exercise therapy is a common
      intervention in treating OA, with primary aims of improving functional movement
      and managing the problems associated with abnormal functional movement. We review
      the underlying process of exercise treatment and its importance for OA
      disability. A brief description of OA disease and an OA disability model are
      introduced, and then the importance of exercise and trends in prescribing
      exercises for OA are discussed. Finally, future directions and suggestions for
      research in this field are described.

PMID- 15573842
TI  - Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella
      isolated from patients having acute diarrhoeal disease.
AB  - BACKGROUND: Non-typhoidal Salmonella are one of the key etiological agents of
      diarrhoeal disease. The appearance of multiple drug resistance along with
      resistance to quinolones in this bacterium poses a serious therapeutic problem.
      We determined the prevalence of nalidixic acid and ciprofloxacin resistance in
      non-typhoidal Salmonella isolated from faecal samples of patients with acute
      diarrhoeal disease attending the outpatient and inpatient department of a
      hospital in Saudi Arabia during the years 1999 to 2002. METHODS: Non-typhoidal
      Salmonella were isolated from faecal samples. Antimicrobial susceptibility was
      tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacin were
      determined by the agar dilution method. RESULTS: During the study period, 524
      strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup
      C1 were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%,
      respectively). Resistance to ampicillin was observed in 22.9% and to
      trimethoprim/sulfamethoxazole in 18.5% of the strains. Nalidixic acid resistance
      was encountered in 9.9% and ciprofloxacin resistance in 2.3% of the strains.
      Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.5% in
      2002 (P=0.0007) and ciprofloxacin resistance increased significantly from 0.1% in
      1999 to 0.9% in 2002 (P=0.0001). MICs to nalidixic acid and ciprofloxacin were
      determined among 29 nalidixic acid-resistant strains of non-typhoidal Salmonella
      isolated during 2002. The MIC was >256 microg/mL to nalidixic acid and 8 to 16
      microg/mL to ciprofloxacin. CONCLUSION: The increasing rates of antimicrobial
      resistance encountered among non-typhoidal Salmonella necessitate the judicious
      use of these drugs in humans. Moreover, these findings support the concern that
      the use of quinolones in animal feed may lead to an increase in resistance and
      should be restricted.

PMID- 15573843
TI  - Advancing age and the risk of nasal carriage of Staphylococcus aureus among
      patients on long-term hospital-based hemodialysis.
AB  - BACKGROUND: Elevated nasal carriage rates of Staphylococcus aureus and ensuing
      complications among the elderly and in those on long-term hemodialysis (HD) are
      well recognized. The aim of the present study was to determine the extent to
      which advancing age is associated with the risk of persistent S. aureus nasal
      carriage among end-stage renal disease (ESRD) patients on long-term HD. PATIENTS
      AND METHODS: This prospective study involved 205 ESRD patients enrolled for
      maintenance HD from July 1997 to July 2000. Persistent nasal carriage was defined
      by two or more positive cultures for methicillin-susceptible (MSSA) or
      methicillin-resistant S. aureus (MRSA). Five standardized swabs were taken from
      the anterior nares of all the patients on long-term HD. S. aureus nasal carriage
      rates were estimated and compared among ESRD patients of different age groups.
      RESULTS: Overall, a prevalence of 38.05% (78/205) for S. aureus nasal carriage
      was observed, including 27.3% (56/205) for MSSA and 10.7% (22/205) for MRSA.
      Patients aged 75 to 84 years had the highest (84.6%, 11/13) prevalence of S.
      aureus nasal carriage (RR, 7.000, 95% CI, 4.350-11.763, P<0.00001). Those aged 65
      to 74 years had the next highest (49.0%, 25/51) nasal carriage rates (RR, 4.083,
      95% CI, 2.302-7.658, P<0.0001) while patients aged 15 to 24 years (reference
      group) had the lowest (12.8%, 1/8) prevalence of nasal carriage. The 75 to 84
      year age group also had the highest rates of MSSA (46.2%, 6/13), (RR- 3.833, 95%
      CI, 2.144-7.234, P<0.0001) and MRSA (38.5 %, 5/13) (RR, 6.333, 95%CI, 2.767
      16.198, P<0.0001) nasal carriage compared to the reference group. CONCLUSIONS:
      Significantly higher persistent MSSA and MRSA nasal carriage rates among ESRD
      patients >75 years of age are suggestive of an elevated risk of potentially
      serious S. aureus- related complications among the very elderly during long-term
      HD. These findings might be helpful in the identification of elderly HD patients
      as a high-risk group for S. aureus-linked vascular access-related septicemia
      (VRS) and to evolve appropriate preventive strategies.

PMID- 15573844
TI  - Prevalence of hepatitis delta antibody among HBsAG carriers in Saudi Arabia.
AB  - BACKGROUND: There are a paucity of data available on the exact prevalence of
      delta hepatitis among HBsAg positive carriers in Saudi Arabia. The aim of this
      study was to determine the exact prevalence of delta antibody in HBsAg positive
      carriers in Saudi Arabia. PATIENTS AND METHODS: Between January 1996 and January
      1997 the serum of 19,250 patients was tested for HBsAg. HBsAg positive sera were
      subsequently tested for delta antibody. In addition, 3147 healthy blood donors
      underwent HBsAg testing. Those who were HBsAg positive had delta antibody testing
      using the ELISA method. RESULTS: Among 19,250 patients, 780 (4.1 %) were HBsAg
      positive, of which 67 (8.6%) patients were anti-delta positive and 2 (0.25%) were
      anti-delta borderline. Among 3147 healthy donors, 60 (1.9%) were HBsAg positive
      with 2 (3.3%) being delta antibody positive. CONCLUSIONS: The prevalence of delta
      antibody among hospital- and clinic-based HBsAg positive patients was 8.6% and
      among healthy blood donors who were HBsAg positive, the prevalence was 3.3%.
      Furthermore, delta antibody prevalence was 0.06% for "all comers", i.e., healthy
      blood donors. With decreasing hepatitis B prevalence as a result of universal
      vaccination, it is expected that delta hepatitis infection among Saudis will
      decrease with time.

PMID- 15573845
TI  - Interactions between leptin, neuropeptide-Y and insulin with chronic diurnal
      fasting during Ramadan.
AB  - BACKGROUND: Fasting during the month of Ramadan for Muslims is a unique metabolic
      model that includes abstinence from food and fluid intake during the period from
      dawn to sunset as well as a reduction in meal frequency and alterations in the
      sleep-wakefulness cycle. Leptin, neuropeptide-Y and insulin are thought to play
      an important role in long-term regulation of caloric intake and energy
      expenditure. However, the long-term changes and interactions between these
      factors during this pattern of fasting are not known. SUBJECTS AND METHODS: The
      study was conducted on 46 healthy female volunteers (age, 22+/-2 years; BMI,
      25.3+/-0.7 kg/m2). Anthropometrical measurements, estimation of body fat and
      fasting serum levels of neuropeptide Y, leptin, insulin and glucose were
      estimated at baseline (day 1), days 14 and 28 of the month of Ramadan and 2 weeks
      after Ramadan. RESULTS: Baseline serum levels of leptin correlated positively
      with body fat (r=0.87, P=0.0002). Serum leptin levels exhibited a significant
      increase by approximately 41% and neuropeptide-Y levels were decreased by 30.4%
      throughout the month of Ramadan. In addition, a significant correlation (r=0.63,
      P=0.0001) was found between changes in serum leptin and serum insulin. However,
      changes in serum neuropeptide-Y levels did not correlate with those of leptin or
      insulin CONCLUSIONS: Long-term fasting with interrupted nocturnal eating is
      associated with significant elevations in serum leptin and insulin and reduction
      in serum neuropeptide-Y. The changes in serum leptin are likely mediated through
      insulin. However, changes in neuropeptide-Y appears to be mediated independently
      of leptin or insulin during this type of fasting

PMID- 15573846
TI  - Glucose tolerance in pregnant women with vaginal candidiasis.
AB  - BACKGROUND: The use of traditional historic risk factors to identify gestational
      diabetes mellitus (GDM) will miss half of women with gestational diabetes
      mellitus. Our aim was to evaluate whether impaired glucose tolerance is a risk
      factor for vaginal candidiasis in pregnant women. PATIENTS AND METHODS: In a
      cross-sectional study, we compared the prevalence of impaired glucose tolerance
      in 64 pregnant women with vaginal candidiasis (positive microscopy) and 59
      Candida-negative control subjects. Subjects underwent standardized 75-gram oral
      glucose tolerance testing between the 24th and 28th weeks of their pregnancies.
      Patients were included only if they had no known diabetes mellitus or historic
      risk factors for gestational diabetes mellitus, and had not been receiving
      antibiotic or steroid therapy. We compared glucose levels at fasting, 30 minutes,
      60 minutes and 120 minutes, and perinatal and neonatal outcomes in the two
      groups. RESULTS: There were no statistical differences between cases and controls
      in demographic characteristics. Glucose concentrations were higher in pregnant
      women with vaginal candidiasis than in control subjects at fasting (89 vs. 84
      mg/dL, P=0.021), 30 minutes (139 vs. 126 mg/dL, P=0.050), and 60 minutes (124 vs.
      106 mg/dL, P= 0.018) after intake of 75 gram of glucose. The two groups did not
      differ in glucose level at 120 minutes after glucose administration. Gestational
      diabetes prevalence was 3.1% and 3.4% in the study and control group,
      respectively (P=0.274). CONCLUSION: The tolerance to glucose in pregnant women
      with vaginal candidiasis seems discretely impaired.

PMID- 15573847
TI  - Age at menarche and the reproductive performance of Saudi women.
AB  - BACKGROUND: Saudi Arabia has undergone substantial development in the recent past
      with concomitant changes in living conditions, and economic and general health
      status that have affected the age at menarche in Saudi women. We evaluated the
      current age at menarche and reproductive events among Saudi women. SUBJECTS AND
      METHODS: Age, age at menarche, age at marriage, age of first pregnancy, number of
      children, and number of abortions were collected for Saudi women attending King
      Khalid University Hospital (KKUH) over a 3-month period in 2002. RESULTS: For 989
      Saudi women, the mean age at menarche was 13.05 years. There was a decrease in
      the age of menarche over the past 20 years, an increase in the age of marriage,
      age of first pregnancy, and a decrease in the number of children and abortions.
      Compared with data from two decades, the age at menarche decreased significantly
      from 13.22 to 13.05 years. CONCLUSION: The decrease in the age of menarche among
      Saudi women indicates better socioeconomic status and improvements in health.

PMID- 15573848
TI  - Laparoscopic management of ovarian dermoid cysts: a review of 47 cases.
AB  - BACKGROUND: Mature cystic teratomas, often referred to as dermoid cysts, are the
      most common germ cell tumors of the ovary. In the recent years, transvaginal
      sonographic diagnosis of ovarian dermoid cysts together with laparoscopic
      approach have greatly improved the treatment of this benign lesion. We
      retrospectively reviewed the outcome of laparoscopic surgery for suspected
      ovarian dermoid cysts. PATIENTS AND METHODS: The preoperative findings, operative
      techniques and postoperative complications were retrospectively reviewed in women
      who underwent laparoscopic surgery for dermoid cysts, between January 2000 and
      May 2003. RESULTS: In 47 women aged 21 to 53 years (median, 38.8 years), 93.6%
      had a unilateral cyst with a diameter of 17 to 108 mm (median, 51 mm). Clinical
      presentations were pain (62%), abnormal vaginal bleeding (21%) and ovarian
      torsion (2%), whilst 17% were diagnosed incidentally during routine examination.
      Surgery included cystectomy (57%), total (36%) or partial oophorectomy (6.4%) and
      laparoscopy-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy
      (2%). During the cyst extraction, minimal spillage occurred in 42.5% of the cases
      and none developed chemical peritonitis. In 2 patients, conversion to laparotomy
      (4.3%) was required, one for sigmoid colon injury and one for malignant ovarian
      tumor detected via frozen section. The median operating time was 80 minutes
      (range, 35-180 minutes). CONCLUSION: Using strict adherence to guidelines for
      preoperative clinical assessment and intra-operative management, laparoscopic
      treatment of dermoid cysts appears to be a safe procedure.

PMID- 15573849
TI  - Apolipoprotein E polymorphism and lipoprotein levels in a Gulf Arab population in
      Kuwait: a pilot study.
AB  - BACKGROUND: APOE polymorphism is believed to confer susceptibility to coronary
      heart disease (CHD) and Alzheimer's disease. It is well known that patterns of
      APOE polymorphisms differ between populations and ethnic groups, although most of
      the data available so far have been in whites. SUBJECT AND METHODS: We evaluated
      the frequencies of APOE genotypes and their relationships with serum levels of
      lipids, lipoproteins and apolipoproteins in two groups of Gulf Arab citizens: a
      control population of healthy voluntary blood donors (n=106), and a group of
      patients presenting to the lipid clinic for the first time with combined
      hyperlipidaemia (CH) (n=41). In both groups, fasting serum total cholesterol
      (TC), triglycerides (TG), HDL, LDL and apolipoprotein A1 and B levels were
      measured by routine autoanalyzer methods, and APOE genotyping was performed by
      validated PCR methods. The lipid and lipoprotein levels were related to the
      specific APOE allele frequencies. RESULTS: Allele frequencies were 5.7% for *E2,
      85.4% for *E3, and 9.0% for *E4 in the healthy blood donor group. An essentially
      similar pattern was seen in the patients with CH. This APOE allelic distribution
      conforms to patterns described in Chinese, whites and South Asians. In both the
      blood donor and CH groups there were no consistent links between specific APOE
      pattern and serum lipoproteins, as would have been predicted from APO *E2 and APO
      *E4 frequencies. CONCLUSIONS: We conclude that APOE allelic patterns in healthy
      Kuwaiti blood donors and a smaller group of patients with CH do not
      satisfactorily predict circulating blood levels of lipids and lipoproteins.

PMID- 15573850
TI  - Steroid therapy for post-tonsillectomy symptoms in adults: a randomized, placebo
      controlled study.
AB  - BACKGROUND: Post-operative morbidity following tonsillectomy remains an important
      clinical problem despite advances in anesthetic and surgical techniques. This
      study investigated the effect of a one-day course of intravenous dexamethasone on
      recovery from tonsillectomy. PATIENTS AND METHODS: In a double-blind, randomized,
      placebo-controlled trial, 30 consecutive adult patients between 18 and 35 years
      of age, who had no previous or known contraindications to steroid therapy, were
      randomly assigned at the time of surgery to either a 24-hour course of
      dexamethasone (3 doses of 6 mg IV) or placebo with the first dose administered
      during surgery, and subsequent doses given after 8 and 16 hours. The same surgeon
      treated all patients. Postoperative signs and symptoms, including pain, nausea,
      vomiting, progress of healing and the degree of granulation, were evaluated for 2
      weeks. RESULTS: Patients treated with dexamethasone showed significantly less
      pain, nausea and vomiting, better healing and less granulation. There were no
      side effects reported. CONCLUSION: Application of 3 doses of dexamethasone within
      24 hours during and after tonsillectomy is advisable because of the reduction of
      postoperative morbidity, especially pain and edema.

PMID- 15573851
TI  - Cytogenetics and etiology of ambiguous genitalia in 120 pediatric patients.
AB  - BACKGROUND: A newborn with ambiguous genitalia needs prompt evaluation to detect
      life-threatening conditions (e.g., salt-losing crisis in congenital adrenal
      hyperplasia [CAH]) and gender assignment. Sex assignment in these children
      continues to be a challenging diagnostic and therapeutic problem. We studied the
      causes and characteristics of ambiguous genitalia in children who were referred
      to a cytogenetic laboratory. PATIENTS AND METHODS: We retrospectively reviewed a
      total of 120 medical records of patients with a primary indication of ambiguous
      genitalia that were referred to the cytogenetic lab for karyotyping during the
      period of 1989 to 1999. Diagnosis was based on a clinical impression from the
      primary physician, who was primarily a staff pediatrician, endocrinologist and/or
      pediatric urologist. RESULTS: CAH was the underlying cause of ambiguous genitalia
      in 41 of 63 patients with ambiguity due to endocrine causes; 39 of these patients
      showed a 46,XX karyotype and 2 cases were 46,XY (both the 46,XY patients had 3
      beta-hydroxylase deficiency). In 57 patients, ambiguous genitalia were due to
      congenital developmental defects. The most common endocrine case of ambiguous
      genitalia was 21-OH deficiency. Seven patients were classified as idiopathic with
      six showing the 46,XY and one the 46,XX karyotype. Gender was reassigned at birth
      or at diagnosis in 15 patients. CONCLUSION: The etiology of ambiguous genitalia
      is variable. The physician managing these families could minimize the trauma of
      having a child with unidentified sex by providing appropriate genetic counseling
      so that the parents can make an early decision. Prenatal DNA testing in at-risk
      families should be considered and appropriate therapy offered to minimize or
      prevent genital ambiguity.

PMID- 15573852
TI  - What's your diagnosis? Gallstone ileus.

PMID- 15573853
TI  - Effect of rectal lactulose administration with oral therapy on time to recovery
      from hepatic encephalopathy: a randomized study.

PMID- 15573854
TI  - Nonketotic hyperglycinemia in Suleimaniah Children's Hospital, Riyadh, Saudi
      Arabia.

PMID- 15573855
TI  - Comparison of lipid profiles in normal and hypertensive pregnant women.

PMID- 15573856
TI  - Metastatic hepatic carcinoid associated with ectopic ACTH syndrome, resistant to
      octreotide and ketoconazole therapy.

PMID- 15573857
TI  - Capnocytophaga bacteremia in a girl with relapsed acute lymphoblastic leukemia.

PMID- 15573858
TI  - Beta-mannosidae deficiency in two mentally retarded girls with intractable
      seizures.

PMID- 15573859
TI  - Recommendations for the diagnosis and management of osteoporosis.

PMID- 15573860
TI  - Epidemiological, clinical, diagnostic and therapeutic survey of 686 cases of
      brucellosis.

PMID- 15573861
TI  - A neonatal case of citrullinemia with urolithiasis.

PMID- 15573862
TI  - Editorial overview: Tie me up, tie me down: immunosuppressive therapies for the
      21st century.

PMID- 15573863
TI  - Anti-inflammatory inhibitors of IkappaB kinase in asthma and COPD.
AB  - Nuclear factor-kappaB (NFkappaB) is an inducible transcription factor that plays
      a central role in the regulation of many immune and inflammatory responses. While
      NFkappaB is required for cell survival and immunity, abnormal expression and/or
      activation of NFkappaB leads to the development of many pathological states,
      especially those involved in chronic and acute inflammation. Many different
      signal transduction pathways, originating from a wide variety of cellular
      stresses and stimuli, converge on a single target; the NFkappaB/IkappaB complex
      and its activating kinase (inhibitor of kappaB kinase, IKK). Here, we review some
      of the major NFkappaB activating pathways, their role in the pathogenesis of
      asthma and chronic obstructive pulmonary disease (COPD), and their potential as
      targets in the treatment of asthma and COPD.

PMID- 15573864
TI  - G-CSF: boosting endogenous production--a new strategy?
AB  - Granulocyte colony-stimulating factor (G-CSF) has been in clinical use for over a
      decade. Its main applications are in adjunctive medication to chemotherapy and in
      mobilizing stem cells for bone marrow transplantation. However, it has additional
      effects in that it primes neutrophilic granulocytes for improved host defense,
      and reduces the release of pro-inflammatory cytokines. These effects have
      prompted trials for numerous other indications. New research into the production
      and regulation of G-CSF in health and disease may now enable tailored strategies
      to induce or boost G-CSF formation. Similarly, new forms of application may
      increase its effectiveness.

PMID- 15573865
TI  - Selective retinoic acid receptor ligands for rheumatoid arthritis.
AB  - Retinoids, modulators of retinoic acid receptors (RARs), have been studied for
      over 20 years as potential therapeutic agents for rheumatoid arthritis (RA).
      Early successes at the in vitro and in vivo levels were overshadowed by
      disappointing clinical trials that yielded poor efficacy and unacceptable side
      effects. A greater understanding of retinoid biology has led to the development
      of many synthetic retinoids that selectively modulate the RAR isotypes. RAR
      selective retinoids have a high potential for improved pharmacology with reduced
      toxicity, thereby renewing interest for the use of retinoids in RA.

PMID- 15573866
TI  - Sigma receptor ligands: applications in inflammation and oncology.
AB  - Sigma (sigma) receptors were initially proposed as a subtype of opiate receptors,
      and bind several psychoactive compounds. They are classified into sigma 1
      (sigma1) and sigma 2 (sigma2) subtypes. The characterization of these subunits,
      and the discovery of new specific sigma receptor ligands, demonstrated that sigma
      receptors belong to a specific entity distinct from opiate receptors. Radioligand
      binding data have recently demonstrated that the sigma1 subtype is related to a
      sterol isomerase, which is involved in the cholesterol biosynthesis pathway, and
      also to another protein of unknown function, SRBP2 (SR-31747 binding-protein 2),
      which shares a high homology with this enzyme. This complex group of proteins
      also binds molecules devoid of central effect, which demonstrate potent anti
      inflammatory properties, and so are potentially useful in pathologies where pro
      inflammatory cytokines are involved, particularly rheumatoid arthritis, Crohn's
      disease or psoriasis. In addition, the two sigma receptor subtypes and their two
      related proteins are also expressed on tumor cells, where they could be of
      prognostic relevance, and their ligands could potentially be used in the
      detection and targeting of tumors.

PMID- 15573867
TI  - Synthetic small-molecule complement inhibitors.
AB  - During the past few years, several large molecular-weight compounds with
      complement-inhibitory activities have entered clinical trials for a wide variety
      of acute and chronic inflammatory conditions. Various small synthetic compounds
      that offer several advantages over the larger complement inhibitors are also
      being discovered at a rapid pace. In this review, the focus will be on three of
      these small molecules, a C3-binding peptide, compstatin; a synthetic peptidic
      antagonist of the C5a anaphylatoxin receptor, 3D53; and a non-peptidergic
      antagonist of the C3a anaphylatoxin receptor, SB-290157. In recent years,
      compstatin has undergone a series of optimizations that have led to more active
      and stable analogs, while 3D53 and SB-290157 have been more extensively tested in
      animal models of various human inflammatory diseases. These compounds have been
      shown to be effective and display little or no toxicity, and as such may be
      promising new candidates for further therapeutic development.

PMID- 15573868
TI  - Histamine H4 receptor antagonists: the new antihistamines?
AB  - Antihistamines (histamine H1 receptor antagonists) are a mainstay treatment for
      atopic allergy, yet they are only partially effective in relieving the symptoms
      of the disease. They also have very limited value for the treatment of asthma,
      despite the well-characterized bronchoconstrictory effects of histamine. The
      recent discovery of a fourth histamine receptor (H4), and the realization that it
      is exclusively expressed on hematopoietic cell types that are most implicated in
      the development and symptomatology of allergy and asthma, suggests that
      pharmacological targeting of the H4 receptor, either alone or in combination with
      H1 receptor antagonists, may prove useful for treating both allergy and asthma.
      Here we review the known biology associated with the H4 receptor, as well the
      effects of a highly selective H1 receptor antagonist.

PMID- 15573869
TI  - Can helminth antigens be exploited therapeutically to downregulate pathological
      Th1 responses?
AB  - In developing countries where helminth infections are highly prevalent, Th1
      autoimmune diseases are almost never reported. A hypothesis suggesting that this
      may be due to effects of helminth infection on the immune system has been
      developed, and has inspired scientists to explore the possibility of using
      helminth antigens to treat autoimmune diseases. In animal models, helminth
      infection and helminth products have been successfully used to prevent different
      Th1-mediated autoimmune diseases. Results from initial studies were interpreted
      based upon the Th1/Th2 paradigm: A Th2-polarizing helminth infection correcting a
      Th1 autoimmune 'imbalance'. Intriguingly, however, allergies rarely develop in
      the host, despite the strong Th2 polarization induced by parasite antigens.
      Helminth infections act on the immune system of the host at many different
      levels. For this reason, identifying one or more products with therapeutic
      potential, from the 20,000 genes that a helminth can express, is a challenging
      task. In this review, we summarize the results achieved in animal models, and
      suggest possible approaches for the design of therapies appropriate for use in
      human Th1-mediated autoimmune pathologies.

PMID- 15573870
TI  - COLAL-PRED Alizyme.
AB  - COLAL-PRED (prednisolone sodium metasulfobenzoate), which is targeted to the
      colon by COLAL colonic drug delivery technology, is being developed by Alizyme
      for the potential treatment of inflammatory bowel disease. Alizyme expect to
      initiate a phase III trial in 2005.

PMID- 15573871
TI  - IDN-6556 Idun Pharmaceuticals Inc.
AB  - IDN-6556 is a lead compound from a class of small-molecule caspase protease
      inhibitors, and is currently under development by Idun as a potential treatment
      for acute alcoholic and infectious hepatitis. In October 2003, a phase II trial
      of IDN-6556 began in 100 patients undergoing liver transplantation.

PMID- 15573872
TI  - SCIO-469 Scios Inc.
AB  - SCIO-469 is a small-molecule p38 mitogen-activated protein (MAP) kinase inhibitor
      under development by Scios Inc as a potential oral therapy for inflammatory
      disorders. By July 2004, SCIO-469 was in phase lib clinical trials for rheumatoid
      arthritis.

PMID- 15573873
TI  - Bertilimumab Cambridge Antibody Technology Group.
AB  - Cambridge Antibody Technology (CAT) is developing bertilimumab, an anti-eotaxin-1
      monoclonal antibody, for the potential treatment of allergic disorders. By
      September 2003, CAT had released results from phase I/II trials, and was seeking
      to outlicense rights for bertilimumab.

PMID- 15573874
TI  - [Treatment of blast injuries of the hand].
AB  - INTRODUCTION: Blast injuries of the hand result from the manipulation of handmade
      explosives, the blast causes most damage in the first web. Our purpose is to
      propose a classification of these injuries so as to lead to a therapeutic
      strategy. METHOD: We report a series of nine blast injuries of the hand in eight
      patients of average age 24 years. The aetiologie was handmade explosive
      manufacture (five cases) and the manipulation of munitions (four cases). Five
      hands presented an amputation of the thumb together with the index and in three
      of them, the long finger was involved as well. Only one thumb was revascularised
      successfully. Four thumbs were reconstructed, two by toe transfer, and two by
      "index bank". DISCUSSION: We observed four different stages: Stage 1: Isolated
      musculo-cutaneous injury. An intermetacarpal pin avoids first web contracture.
      Skin coverage is achieved by a pedicled local flap or a skin graft. Stage 2:
      Osteo-articular injuries of the thumb and second ray but sparing the trapezo
      metacarpal joint. The thumb reconstruction is often based upon rinciple. Stage 3:
      Characterised by a destructive injury of the trapezo-metacarpal joint. Stage 4:
      Amputation or devascularization of the thumb. Extensive vascular injuries
      neccessitate a bypass from a healthy zone. The amputations, which are mostly
      proximal, require a preliminary osteocutaneous reconstruction of the first
      metacarpal before any toe transfer. Finger translocations are made difficult
      because of the high rate of serious injuries of the index and palm.

PMID- 15573875
TI  - [Short term results of total carpometacarpal joint replacement surgery using the
      ARPE implant for primary ostearthritis of the thumb].
AB  - INTRODUCTION: We have reviewed the short-term results of the ARPE arthroplasty of
      the first carpometacarpal joint for osteoarthritis of the thumb. MATERIAL AND
      METHODS: One hundred and eighteen patients have been operated on in our
      department between June 1999 and June 2003, by the same surgeon. Sixty-three of
      these patients had been followed for a minimum of six months and were included in
      this retrospective study. We have evaluated functional results as pain, key
      pinch, mobility and patient satisfaction. The occurrence of complications was
      investigated. RESULTS: The results of this procedure were found to be excellent
      for pain, mobility and strength. Recovery was judged fast and patient
      satisfaction was high. The most frequent complication was implant luxation in six
      cases. Implant loosening was seen in three. DISCUSSION: Functional results of
      this type of arthroplasty are excellent. We consider it to be superior to
      trapeziectomy for recovery (rehabilitation is unnecessary) and strength. Most
      common complications have a relatively simple surgical solution. Trapeziectomy
      remains possible thanks to a minimal shortening of the metacarpal bone.
      CONCLUSION: The ARPE arthroplasty can be considered as a good surgical option for
      treatment of thumb osteoarthritis. A longer follow up is necessary to predict the
      long-term behaviour of the prosthesis.

PMID- 15573876
TI  - [Jaccoud's arthropathy. Surgical results of 41 hands].
AB  - Jaccoud's arthropathy, which was first described in 1869, is a rare syndrome that
      is characterized by a painless or relatively painless deformity of the digits II,
      II, IV and V with a dislocation of the extensor tendons into the metacarpal
      valley. When the thumb is affected, a Z deformity is observed. The present
      analysis was based on 40 patients (56 hands, 41 of which were operated on over
      the period 1989 to 2001). A distinction should be made between Jaccoud's disease
      following a known inflammatory arthropathy (23 hands; average patient age 55
      years) and the idiopathic form of the disease (18 hands, average patient age 70
      years). From a clinical point of view, a classification of the deformities is
      needed so that appropriate surgical treatment can be determined. In the present
      study, four groups were therefore proposed, in groups I and III the realignment
      to centre of the extensor tendons of the metacarpophalangeal joint and joint
      stabilization yielded 83% positive results. In groups II and IV the results were
      only 66% good after Swanson implant. The pathogenesis of Jaccoud's disease has
      not yet been determined, but now that more information has become available and a
      better analysis can be made of its various clinical and anatomopathological
      charasteristics, these should assist in defining precise surgical indications.

PMID- 15573877
TI  - Marchetti nailing of closed fresh humeral shaft fractures.
AB  - INTRODUCTION: The purpose of this study was to analyse the results of Marchetti
      nailing. METHOD: Between 1995 and 2003, 143 patients with closed fresh humeral
      shaft fractures were treated with the Marchetti-Vicenzi nail. The fractures were
      classified according to the AO classification: 37 A1, 24 A2, 25 A3, 22 B1, 15 B2,
      7 B3, 7 C1, 4 C2 and 2 C3. RESULTS: Fracture healing was obtained in 136 cases.
      The mean healing time was 11 weeks. There were seven non-unions. The range of
      motion of the shoulder was excellent in 95 patients (66.4%), moderate in 43 (30%)
      and poor in five (4.2%). The elbow had an excellent range of motion in 89
      patients (62.2%), moderate in 48 (33.5%) and poor in six (4.2%). The functional
      result was excellent in 56 patients (39.1%), good in 62 (43.3%), fair in 18
      (12.6%) and poor in seven (4.9%). CONCLUSION: Marchetti-Vicenzi nailing appears
      to be a good method for the treatment of humeral shaft fractures. It is
      technically easy and its results are satisfactory.

PMID- 15573878
TI  - [Surgical repair of flexor tendon pulley rupture in high level rock climbing].
AB  - INTRODUCTION: Twelve high-level rock climbers were operated on for flexor tendon
      pulley rupture. Circumstances of pulley rupture and contributing factors are
      studied; postoperative improvement is evaluated by rock climber level increase,
      compared to the initial level. METHOD: Average age was 28 years and there were
      nine males and three females; all of them were high-level rock climbers,
      succeeding at least in 7a climbing ways before the accident. The surgical
      procedure was to replace the deficient pulley using an extensor retinaculum
      graft. RESULTS: The non-dominant hand was the most frequently involved, and
      especially A2 pulley of the fourth finger. Diagnosis was easy and clinically
      established. DISCUSSION: Medical or functional treatments never allowed climbers
      to reach their former level. The only efficient treatment was surgical, whatever
      the time elapsed between injury and surgery. After this surgical procedure, five
      of the twelve patients improved their results, five recovered their former level
      and two decreased. The results are analysed and compared to other surgical
      procedures. CONCLUSION: Surgical repair of rupture of flexor tendon pulley during
      sport is the only efficient treatment allowing the rock climber to recover and
      improve its performance.

PMID- 15573879
TI  - [Dynamic correction of static scapholunate instability using an active tendon
      transfer of extensor brevi carpi radialis: preliminary report].
AB  - We present the case of a twenty year old man who developed static scapholunate
      instability on the right side following a road traffic accident seven months
      previously. A dynamic surgical technique was devised to treat this problem using
      the tendon of extensor brevi carpi radialis as an active transfer. The tendon,
      divided at its insertion on the base of the third metacarpal, was reinserted into
      the distal part of the scaphoid using two anchors after shortening it by removing
      the distal centimetre. The tendon was rerouted via a pulley created 'de novo' at
      Lister's tubercle in order to centre the tendon on the same axis as the scaphoid.
      No other material was used for bone fixation. The wrist was immobilized in
      extension for six weeks. The clinical and radiological result eight months after
      the intervention showed excellent reduction of the scapholunate joint and a pain
      free wrist with satisfactory mobility.

PMID- 15573880
TI  - [Spontaneous rupture of extensor pollicis longus in systemic lupus
      erythematosus].
AB  - We report a case of spontaneous rupture of extensor pollicis longus of the left
      hand. This 63 year-old woman was treated with oral corticosteroids for 23 years
      because of systemic lupus erythematosus. Her hands had no deformity. This rupture
      was spontaneous and caused pain for 15 days. The treatment was surgical and
      consisted of an extensor indicis proprius transposition. There was no macroscopic
      tenosynovitis. The follow-up of one year showed a good result. Less than 40
      spontaneous ruptures in systemic lupus erythematosus have been described in the
      literature; only seven cases were ruptures of hand tendons and only extensors. As
      far as we know, the spontaneous rupture of extensor pollicis longus has never
      been described in systemic lupus erythematosus. The role of corticosteroids is
      discussed.

PMID- 15573881
TI  - [Bone tuberculosis of the thumb unmasked by injury].
AB  - Tuberculous dactylis is uncommon, which makes it difficult to differentiate from
      tumorous and metabolic affections. Histological analysis constitutes a reliable
      and easy way to achieve a positive diagnosis, especially as the bacteriological
      findings can be negative. We report the case of a 43-year-old woman who consulted
      for a painful right thumb following an injury. Radiographs showed a fracture of
      the proximal phalanx through a lytic lesion. Pathology examination of a biopsy
      specimen revealed granulomata with caseous necrosis, specific to tuberculosis.
      The clinical signs and radiographs resolved after anti-tuberculosis treatment for
      12 months.

PMID- 15573882
TI  - [Neurosteroids and their biological significance].
AB  - The paper summarizes the current knowledge concerning various aspects of
      neurosteroid metabolism and mode of action. These steroid compounds including
      dehydroepiandrosterone, pregnenolone, and their sulfates, as well as progesterone
      and its tetrahydro metabolites, are synthesized de novo in glial cells of
      different brain structures both in humans and in animals. Biological effects of
      neurosteroids and their fundamental and clinical aspects are reviewed.

PMID- 15573883
TI  - [Neurogenesis in the mature olfactory bulb and it's possible functional
      destination].
AB  - This review is concerned with neurogenesis in the mature mammalian brain with
      emphasis on cell population renewal in the olfactory bulb (OB). The structural
      and functional features of the OB are considered along with data on neurotropic
      viruses and toxic dust penetration into the CNS through the OB. We hypothesize a
      protective role of neurogenesis in the mature OB. This suggests that normal
      renewal of cell populations in the OB is an important barrier mechanism
      protecting the brain from invasion of small amounts of harmful neurotropic agents
      (ex. viruses and particles of toxic dust), which can cause various
      neurodegenerative diseases.

PMID- 15573884
TI  - [Dynamic changes of brain serotonergic and dopaminergic activities during
      development of anxious depression: experimental study].
AB  - Chronic psychoemotional stress of social defeats produces development of
      experimental anxious depression in male mice similar to this disorder in humans.
      5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different
      brain areas were investigated at different stages of development of experimental
      disorder. It has been shown that initial stage (3 days of social stress) is
      accompanied by increase of 5-HT level in some brain areas. Decreased 5-HIAA
      levels in the hippocampus, amygdala and nucleus accumbens were discovered at the
      stage of forming depression (10 days of social stress). Pharmacological
      desensitisation and decreased number of 5-HT1A-receptors were shown in frontal
      cortex and amygdala. At the stage of pronounced depression (20 days of stress),
      there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding
      hypothalamus) of depressive animals. However increased number of 5-HT1A-receptors
      and decreased affinity in amygdala and decreased TPH and MAOA activities in
      hippocampus were found in depressive mice. Hypofunction of serotonergic system is
      suggested at the stage of pronounced depression state in animals. Similar
      processes had place in brain dopaminergic systems. It is concluded that dynamic
      changes of brain monoaminergic activities accompany the development of anxious
      depression in animals. Various parameters of monoaminergic systems are
      differently changed depending on brain area, mediator system and stage of
      disorder.

PMID- 15573885
TI  - [The limbical mechanisms of regulations of respiratory neurons in hypoxia
      conditions].
AB  - The structures of limbic system have great integration in vegetative reactions.
      In the oxygen deficiency conditions we studied influence of irritation of
      limbical cortex, orbitofrontal cortes, hipotalamys, septum and hippocampus (CA1
      and CA3 areas) on the impulse activity of respiratory neurons. Phases of hypoxia
      were the model of experiment. Irritation some of this structures on normoxia and
      4-5 thousand meters higher, we discover inhibiting influense on respiratory
      neurons; some structures irritation had activating influence. In difficult
      conditions of hypoxia (7.5-8 thousand meters) on the reduction of the impulse
      activity of neurons, stimulation induced uncharacteristic reactions. Those
      different reactions of irritation limbic structures have regulation sense on
      respitatory neurons.

PMID- 15573886
TI  - [Interaction of psychoemotional state and activity of the immune system].
AB  - As shown, there are direct and reverse functional connections between nervous and
      immune systems. Different shifts in psychoemotional reactivity induced by chronic
      stress or mental depression are accompanied with immunological disturbance, and
      on the contrary, disorders of immune state may be source of changes in mental
      functions. The pineal hormone melatonin, anxiolytic and antidepressant drugs
      simultaneously influences on the cerebral structures and immune system. These
      effects may be important part of specific psychopharmacological activity of the
      drugs.

PMID- 15573887
TI  - [Histophysiology of hair follicles: current concept].
AB  - Hair follicle histophysiology importance isn't limited by hair role in
      psychosocial consequences. More scientists consider the hair follicle as an
      attractive system for studying major biological phenomena because the hair
      follicle is a regenerating system. In this review we revisit the current
      information about histophysiology and control of hair follicle cycling. All
      mature follicles undergo a growth cycle consisting of following phases: growth
      (anagen), regression (catagen) and rest (telogen). We attempt to integrate the
      morphology with the physiology and molecular biology. Hair follicles are
      influenced by environmental, systemic and local factors. The most interesting
      point of this problem is discussed--an integral regulation of hair follicle cycle
      by systemic, intertissue and intercellular interactions.

PMID- 15573888
TI  - [Long way of author to readers (about N.A. Bernshtein works)].

PMID- 15573889
TI  - [Currently central problems of brain physiology and neurology at Conference of
      the Polish Society of Epileptology. Epileptologia].

PMID- 15573890
TI  - [Decreased first-phase secretion of insulin may play a role in the development of
      insulin resistance].
AB  - Decreased first-phase secretion of insulin may play a role in the development of
      insulin resistance. In the development of type 2 diabetes an abnormal function of
      the beta-cells and insulin resistance of liver, fat cells and muscle play the
      main role. An early sign of beta-cell damage can be the loss of first-phase
      insulin response. This is supposed to precede the development of insulin
      resistance. Decrease of first-phase secretion of insulin can induce early
      postprandial hyperglycaemia and hypertriglyceridaemia damaging endothelium of
      precapillary arterioles of the nutritive capillaries. Insulin-induced endothelium
      dependent dilation of these arterioles is inhibited by high glucose and
      triglyceride levels preventing metabolic effect of insulin on the parenchymal
      cells surrounded by nutritive capillaries and leading this way to insulin
      resistance. Second-phase hyperinsulinaemia develops in the impaired glucose
      tolerance. With the progression of the disease into the type 2 diabetes, insulin
      secretion decreases in the second-phase, as well. Because of decrease of first
      phase insulin secretion in type 2 diabetic patients, early insulin therapy could
      be a choice of treatment in type 2 diabetes. Results of the UKPDS suggest that
      insulin-treated type 2 diabetic patients are longer in the near-euglycaemic state
      compared to those treated by oral hypoglycaemic agents. Recent data support that
      early insulin therapy of type 2 diabetic patients retains their own insulin
      secretion capacity and results in lower haemoglobin A1c. A comparison of before
      meal rapid-acting insulin analogue and bedtime NPH insulin regimens verified that
      rapid-acting insulin analogue decreased haemoglobin A1c compared to NPH insulin
      treatment in type 2 diabetes. On the basis of these data arises the possibility
      of the change of the attitude "Oh no, not insulin in type 2 diabetes" to the
      "early rapid-acting insulin analogue treatment" of these patients.

PMID- 15573891
TI  - [Therapy of bronchial asthma in childhood].
AB  - The aim of the study is to summarize the up-to-date therapy of bronchial asthma
      in childhood. Many children in the world (1-30%) suffer from this disease. The
      essence of it is the special allergic inflammation of the bronchi, so the chief
      aim of the therapy is the diminution of this inflammation and the ceasing of the
      actual symptoms. The therapy is based on three possibilities: diminution of the
      causative allergens and trigger factors in the environment, drug therapy, and
      allergen vaccination (immunotherapy). The drug therapy is considered on the four
      step severity criteria of the WHO. The study makes known the basic properties of
      the important drugs and the practice of the therapy; gives a list of elimination
      possibilities and mentions the chief features of immunotherapy.

PMID- 15573892
TI  - [The role of bronchoscopy in examination and treatment of esophageal tumours].
AB  - The role of bronchoscopy in examination and treatment of esophageal tumours. The
      esophageal tumours are diagnosed in many cases in inoperable stage, and if a
      surgical resolution is possible, it's a heroic, great operation with high
      mortality rates and poor results. The involvement of great airways should be
      explored preoperatively by imaging methods, but bronchoscopy is also mandatory.
      The authors report their one year's experience of 121 bronchoscopic examinations
      in esophageal cancer patients. The finding was negative in 40.5% of all
      examinations, and 29.7% was concerned the cancer propagation to bronchial system.
      29.8% of all examinations resulted a suspicion of propagation. The opinion of
      bronchologist can be decisive postoperatively if a fistula is suspected, or after
      an esophageal stent implantation airway symptoms occur. Bronchoscopy is a
      standard method for removal of airway excretion. The author's overview is
      comparing their fifteen years experience with international literature.

PMID- 15573893
TI  - [Ebstein's anomaly--experiences with surgical treatment in adulthood].
AB  - INTRODUCTION: Long time results with operative treatment of Ebstein anomaly were
      examined. PATIENTS AND METHODS: From January 1985 to March 2001 16 patients with
      Ebstein anomaly were operated on. Ages ranged from 16 to 49 years at the time of
      operation. In 7 cases tricuspid valve repair was possible, and in 9 cases
      prosthetic valve was inserted. In all but one biological prosthesis has been
      used. In 15 cases atrial septal defect occurred as a concomitant anomaly, which
      was closed by direct suture in 9 cases and with patch (2 Dacron, 4 pericardium)
      in 6 cases. RESULTS: There was no early death (30 days postoperatively). 1
      patient following tricuspid repair was reoperated on at the 9th postoperative day
      because of significant tricuspid insufficiency. Tricuspid valve replacement was
      performed with a biological prostheses. There were 3 late deaths: 2 patients
      (12.5%) in the first postoperative year (1 cardiac cause, 1 unknown), 1 patient
      died 6 years postoperatively following reoperation. There were 3 more patients
      requiring reoperation (total reoperation rate 28.6%) one of them a few days after
      the primary operation and two others 9 and 11 years following the first
      operation. 13 patients were recalled to control investigations. The authors could
      not contact 2 patients, 1 patient living abroad could not appear at our clinic.
      10 patients have been investigated 6 months to 16 years after the operation.
      There were 9 patients in New York Heart Association class I or II. 2 patients had
      their own repaired valve; both had tricuspid insufficiency grade III. Both were
      completely active. 8 patients had previously tricuspid valve replacement and good
      valve function, but six of them have not been working any more. There were 5
      female patients under 35 at the time of operation and 2 of them had successful
      pregnancies. CONCLUSIONS: Patients with Ebstein anomaly in NYHA stage III-IV. can
      be successfully treated surgically.

PMID- 15573894
TI  - [Treatment of hepatitis B].
AB  - Treatment of hepatitis B. Treatment of acute icteric hepatitis B is similar to
      the principles of treatment of acute hepatitis syndrome. Special care must be
      given to the possibility of fulminant outcome and to the trend to chronicity.
      Diagnosis and treatment of chronic hepatitis B serves prevention of liver
      cirrhosis and hepatocellular carcinoma as well as elimination of the sources of
      further infections. Interferon-alpha treatment results in sustained clinical and
      virological response in about half of the patients. Nucleoside analogues as
      lamivudine, entecavir, adenovir dipivoxil are the alternatives. They are
      effective also in endstage liver cirrhosis caused by hepatitis B virus and able
      to prevent reinfection and graft loss after liver transplantation. Evaluation of
      the benefits and disadvantages of the antiviral agents help to determine the
      individual, patient-tailored treatment.

PMID- 15573895
TI  - [The treatment of acute ischemic stroke].

PMID- 15573896
TI  - [Immunomodulating activity of polyunsaturated phospholipids and regulators of
      energy metabolism in toxic anemia].
AB  - Possible potentiation of the immunomodulating effects of carbohydrate and lipid
      metabolism regulators by their use in combination with polyunsaturated
      phospholipids was studied. The polyunsaturated phospholipids in toxic anemia
      icreased the immunomodulating effects of thiamine and inosine which activated
      glucose catabolism in erythrocytes. The combined use of the polyunsaturated
      phospholipids and thiamine normalized the oxidation--energy status and lowered
      manifestation of the immunosuppressing properties of light erythrocytes in
      laboratory rats exposed to hemolytic poison. The use of the combination of the
      polyunsaturated phospholipids and inosine normalized the oxidation--energy status
      and induced manifestation of the immunomodulating properties in heavy
      erythrocytes of the poisoned rats. The globulin fraction of the rat serum
      containing antibodies to erythrocytes of the poisoned rats exposed to the
      polyunsaturated phospholipids and inosine increased the immunity status of the
      poisoned rats treated with the above mentioned agents. Carnitine and biotin in
      combination with the polyunsatured phospholipids showed no effect on the
      phagocytic and metabolic activity of leukocytes and the immunity status of the
      rats exposed to hemolytic poison.

PMID- 15573897
TI  - [Antitumor effect of natural avermectins].
AB  - The effects of the natural avermectin complex, aversectin C and individual
      avermectin B1 on the growth of ascitic and solid transplantable tumors in animals
      were studied. The results showed for the first time that both aversectin C and
      avermectin B1 possessed marked antitumor activity. In subtoxic doses aversectin C
      significantly inhibited the growth of P388 lymphoid leukemia and Ehrlich
      carcinoma, both ascitic and solid ones. In some administration regimens
      aversectin C inhibited the tumor growth by 70 to 80%. The highest effect of
      aversectin C was observed after its intraperitoneal administration. Avermectin B1
      inhibited the growth of solid Ehrlich carcinoma and carcinoma 755.

PMID- 15573898
TI  - [Aminoglycoside resistance in gramnegative pathogens of nosocomial infections in
      Russia].
AB  - The study of the mechanisms of aminoglycoside resistance in gramnegative
      pathogens of nosocomial infections in 14 hospitals of Russia showed that the
      basic mechanism was production of aminoglycoside modifying enzymes, mainly
      adenylyl transferase ANT(2"), acetyl transferases AAC(3)-V and ACC(6)-I, and
      phosphotransferases APH(3')-I and APH(3')-VI. In all the hospitals enzymes
      modifying gentamicin and tobramycin were wide spread while the resistance
      phenotypes to aminoglycosides were different in separate hospitals. Isepamycin
      proved to be the most active aminoglycoside. Recommendations for the use of
      antibiotics in hospital formulas and empiric therapy should be developed on the
      basis of the local specific features of the resistance in nosocomial pathogens to
      aminoglycosides.

PMID- 15573899
TI  - [Biological activity of fucoidans from brown algae and the prospects of their use
      in medicine].

PMID- 15573900
TI  - [Efficacy and safety of levofloxacin in low respiratory tract infection].

PMID- 15573901
TI  - HB 1028 author explains how 'a good bill died,' advises hospitals on upcoming
      tort reform battle.
AB  - State Rep. Alan Powell wants to set the record straight. Since the final day of
      the 2004 Georgia General Assembly in April, he's been bothered by reports blaming
      House Democrats for preventing the passage of tort reform legislation. He's also
      frustrated by the way opponents took his own bill, HB 1028 (which would have
      established a state-sponsored self-insurance pool for hospitals, and physicians)
      modified it and killed it during the session's last day. Recently, Rep. Powell (D
      23rd), who has served in the Georgia General Assembly since 1990, sat down with
      GHA TODAY's editor to give his perspective about the tort reform battle earlier
      this year while giving Georgia hospitals advice about next year's continued
      effort to reform Georgia's broken civil justice system. Some of Rep. Powell's
      comments were edited for space considerations.

PMID- 15573902
TI  - Containing rising health care costs--a long-standing dilemma.

PMID- 15573903
TI  - First HIPAA privacy conviction: beware of employee violations.

PMID- 15573904
TI  - Spreading HOPE in Georgia's communities.

PMID- 15573905
TI  - Hepatic decompensation after gastric bypass surgery for severe obesity.

PMID- 15573906
TI  - Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal
      barrier dysfunction and oxidative stress.
AB  - The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA)
      on intestinal permeability (IP) and reactive oxygen species (ROS) generation in
      indomethacin-induced enteropathy, a well-known experimental model of Crohn's
      disease. Seventy-eight male Wistar rats were randomly assigned to receive
      indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a
      significant increase in the fraction of urinary excretion of 51Cr-EDTA following
      oral administration (7.9 +/- 1.3 vs 2.3 +/- 0.2%; P < 0.05) and lucigenin
      amplified chemiluminescence in intestinal fragments ex vivo (10.1 +/- 1.9 vs 2.6
      +/- 0.4 cpm x 10(3)/mg; P < 0.05) compared to controls. UDCA significantly
      reversed these effects (P < 0.05), without being incorporated in biliary bile
      acid composition (HPLC analysis). These findings support a local protective
      effect of UDCA in experimental ileitis by the modulation of intestinal barrier
      dysfunction and oxidative stress. In short, they provide insights into mechanisms
      of action of UDCA in intestinal inflammation and a new perspective on the
      treatment of Crohn's disease.

PMID- 15573907
TI  - Prevalence of hepatic granulomas in chronic hepatitis B.
AB  - An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C
      patients is reported, and their presence is considered to be a predictor of
      treatment success. However, there is only one prevalence study on granuloma in
      chronic hepatitis B, and its significance for treatment outcome is unknown. We
      aimed to determine the prevalence of hepatic granulomas in a larger group of
      chronic hepatitis B patients and to compare their presence with the response to
      interferon therapy. Biopsy specimens of chronic hepatitis B patients were
      reevaluated for the presence of hepatic granulomas. All patients with hepatic
      granuloma were screened for other granulomatous diseases by tuberculin skin test,
      chest X-ray and computed tomography, venereal disease research laboratory,
      Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663
      cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%).
      The granulomas could not be ascribed to any other reason. Of the 10 patients with
      hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were
      nonresponders. We conclude that hepatic granuloma is a rare finding in chronic
      hepatitis B and its presence does not seem to predict the response to interferon
      therapy.

PMID- 15573908
TI  - Dietary composition and nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a common and potentially serious form
      of chronic liver disease that occurs in patients who do not abuse alcohol.
      Present dietary recommendations for all Americans, including those with NAFLD,
      endorse a low-calorie, low-fat diet. However, little is known about the effect of
      diet composition on liver histopathology in patients with NAFLD. The aim of this
      study was to determine whether overall calorie intake and diet composition are
      associated with the severity of NAFLD histopathology. Seventy-four consecutive
      morbidly obese patients presenting for bariatric surgery from January 2001 to
      March 2002 were retrospectively reviewed. In addition to a standard surgical and
      psychological evaluation, all patients underwent a preoperative dietary
      evaluation using a standardized 24-hr food recall. Food intake was evaluated for
      total calories and macronutrients and compared to liver histopathology from
      biopsies routinely obtained during surgery. Associations with the severity of
      steatosis and the presence of inflammation or fibrosis were assessed separately
      using chi-square for categorical variables and ANOVA for continuous variables.
      Further, we conducted multiple logistic regression analyses for each histological
      outcome. There were no significant associations between either total caloric
      intake or protein intake and either steatosis, fibrosis, or inflammation.
      However, higher CHO intake was associated with significantly higher odds of
      inflammation, while higher fat intake was associated with significantly lower
      odds of inflammation. In conclusion, present dietary recommendations may worsen
      NAFLD histopathology.

PMID- 15573909
TI  - Patients with autonomic neuropathy are more likely to develop hepatic
      encephalopathy.
AB  - Autonomic neuropathy (AN) is common in patients with chronic liver disease. For
      hitherto unknown reasons, in longitudinal studies, the presence of AN has been
      found to be an independent predictor of mortality in patients with cirrhosis. We
      hypothesized that patients with AN are more likely to develop hepatic
      encephalopathy (HE) due to prologed intestinal transit time. In this study, we
      examined the incidence of new-onset HE in patients with and without AN. Seventy
      two patients (Child A/B/C = 35/31/6) without evidence of HE at the time of
      autonomic function testing (AFT) were followed for 39.5 +/- 27.3 months. The end
      point of the study was the development of new onset HE. Patients were followed
      until death or liver transplantation. Of the 72 patients, 42 (58%) patients did
      not develop HE (group A) while 30 (42%) developed HE (group B) during the follow
      up. Both groups had similar baseline demographics. AN was more common in group B
      (27/30; 90%) compared to group A (28/42; 67%) (P = 0.02). Kaplan-Meier analysis
      showed a trend toward a higher incidence of HE in patients with AN. Mortality was
      higher in group B (12/30; 40%) compared to group A (8/42; 19%) (P = 0.04).
      Patients with AN were more likely to develop new onset HE. Although an
      independent effect of AN on HE was not established in this study, we speculate
      that delayed intestinal transit secondary to AN may explain the higher incidence
      of HE in patients with AN.

PMID- 15573910
TI  - Effect of losartan, an angiotensin II antagonist, on hepatic fibrosis induced by
      CCl4 in rats.
AB  - In addition to regulating blood pressure and body fluid homeostasis, the renin
      angiotensin system (RAS) is also involved in hepatic fibrogenesis. We aimed to
      investigate the effect of losartan, an angiotensin II (Ang II) antagonist, on
      CCl4-induced hepatic fibrosis in rats. Hepatic fibrosis was induced by a
      subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4
      administered was 1 mg/kg. Alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels in plasma and hydroxyproline (Hyp) contents in
      liver tissue were assayed by spectrophotometry. Hyaluronic acid (HA) and
      procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor
      alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in
      culture supernatants of Kupffer cells (KCs) stimulated with Ang II was determined
      by ELISA. Liver samples collected after 12 weeks of CCl4 treatment were stained
      with hematoxylin and eosin, then scored. Losartan (2.5, 5, and 10 mg x kg(-1),
      ig) and captopril (100 mg x kg(-1), ig) significantly decreased liver and spleen
      indexes, serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp
      contents in liver tissue in rats of hepatic fibrosis. Histopathological scores
      showed that losartan had an inhibitory effect on the progression of hepatic
      fibrosis. In in vitro experiments, losartan (1 x 10(-9) - 1 x 10(-5) M)
      significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of
      KCs, but captopril (1 x 10(-5) M) did not. The results showed that losartan
      significantly inhibited the progression of hepatic fibrosis induced by CCl4, and
      the inhibitory effect of losartan on hepatic fibrosis might be associated with
      its ability to inhibit the production of TNF-alpha and TGF-beta1 by activated
      KCs.

PMID- 15573911
TI  - Treatment of bronchobiliary fistula due to an infected hydatid cyst by a
      nonsurgical approach.

PMID- 15573912
TI  - The adherent gastric mucous layer is composed of alternating layers of MUC5AC and
      MUC6 mucin proteins.
AB  - Mucin-type glycoproteins are the major structural proteins in gastric mucus.
      Stomach mucin proteins include MUC5AC, synthesized by surface foveolar or pit
      cells, and MUC6, synthesized by neck and gland cells. The aim of this study was
      to determine the spatial distribution of these mucin proteins within the
      extracellular mucous coat. Double-labeling immunoflourescence/confocal microscopy
      was used in histologically normal surgical resection specimens. Intralumenal
      mucin within antral glands consisted entirely of MUC6 protein. Intralumenal mucin
      within the gland isthmus region consisted of an irregular mixture of MUC5AC and
      MUC6. The mucous layer on the gastric surface consisted primarily of MUC5AC
      extending in layered sheets with MUC6 protein layered in between. The laminated
      appearance of the surface mucus was present in both H. pylori-infected and
      noninfected specimens. These data indicate that MUC5AC and MUC6 proteins remain
      segregated within the mucous gel in a laminated linear arrangement. The physical
      stratification of mucin proteins may confer increased strength to the mucous
      layer or represent independent and redundant protection.

PMID- 15573913
TI  - Proximal sensor data from routine dual-sensor esophageal pH monitoring is often
      inaccurate.
AB  - Dual-sensor esophageal pH monitoring is routinely used to diagnose GERD. However,
      the proximal sensor may not be in proximal esophagus in patients with shortened
      esophagi. Our objective was to determine how often the proximal sensor was
      misplaced and to determine the effect on pH monitoring. Superior margins of the
      upper and lower esophageal sphincters (UES and LES) were determined prospectively
      in consecutive patients. Dual sensors were placed 20 and 5 cm above the LES with
      a fixed 15-cm spacing pH catheter. Patients were classified into subgroups based
      on the actual location of the proximal sensor. In 661 patients, the proximal pH
      sensor was in the hypopharynx in 9% of patients, within the UES in 36%, and in
      the proximal esophagus in 55%. Spearman's correlation for acid exposure was very
      good between the dual sensors when the proximal sensor was in the proximal
      esophagus (R = 0.76) but was poor when the proximal sensor was misplaced in the
      hypopharynx (R = 0.28). The proximal sensor was misplaced in 45% of patients
      undergoing dual-sensor esophageal pH monitoring. It is important to locate the
      UES by manometry before interpreting the proximal esophageal pH data.

PMID- 15573914
TI  - Endoscopic balloon catheter dilation for treatment of primary cricopharyngeal
      dysfunction.

PMID- 15573915
TI  - Atrophic progression induced by H. pylori infection is correlated with a changing
      pepsinogen I value and associated with the development of gastric cancer.
AB  - It is well known that H. pylori infection induces gastric mucosal atrophy, and
      patients with gastric cancer, which is often complicated by H. pylori infection,
      possess gastric mucosal atrophy including intestinal metaplasia as a background.
      One hundred forty-seven patients with dyspeptic symptom and without gastric
      cancer diagnosed at first endoscopy have been prospectively studied to detect
      early gastric cancer every year by endoscopy for approximately 6 years. The
      status of H. pylori infection was detected by histology and ELISA, the value of
      pepsinogen I (PGI) determined by ELISA, and atrophic pattern determined by the
      histology of multiple specimens. After the follow-up period (mean, 6.1 years), 6
      early gastric cancers had developed in the 49 H. pylori-positive patients with
      transformation of the atrophic pattern, and no cancer had developed in either the
      48 H. pylori-positive patients without transformation of the atrophic pattern or
      the 50 H. pylori-negative patients. There is a significant relationship between
      the incidence of transformation of the atrophic pattern and that of the
      development of gastric cancer in the H. pylori-positive patients. PGI per year in
      the H. pylori-positive group with transformation of the atrophic pattern was
      significantly decreased compared with that in the other two groups. Gastric
      cancers have a background of progressive atrophy, and PGI per year can be a good
      marker to detect gastric cancer at early stages which is developing or has
      developed on the background of atrophic progression.

PMID- 15573916
TI  - Enhanced cell surface expression of matrix metalloproteinases and their
      inhibitors, and tumor-induced host response in progression of human gastric
      carcinoma.
AB  - The cell surface and/or intracellular expression of the matrix metalloproteinases
      (MMP -2, 7, and -9 and MT1-MMP) and their inhibitors (TIMP-2 and -4) were
      investigated in tumor and tumor-infiltrating lymphocytes (TIL) in gastric
      carcinoma (n = 15) from the primary locus, metastatic gastric carcinoma (n = 20)
      from malignant ascites, and benign gastric mucosa (n = 20) for the control. The
      quantitative analysis was based on the percentage of positive cells by flow
      cytometry. The results clearly showed increased cell surface expression of MMP-2,
      -7, and -9, MT1-MMP, and TIMP-2 and -4 in both tumor cells and TIL during the
      development of invasion and/or metastasis of gastric carcinoma. There were
      equilateral correlations with cancer progression and frequency of cell surface
      expression of MMPs and their inhibitors, TIMPs, suggesting not only the
      aggressive nature of particularly metastatic gastric carcinoma, but also the
      presence of MMPs complexed with TIMPs on tumor cells and TIL. The enhanced cell
      surface expression of MMPs and TIMPs on TIL within metastatic carcinoma nests
      showed the result of a host response induced by tumors. These suggest that the
      increased cell surface expression of MMPs and TIMPs, and tumor-induced host
      response play a key role in gastric cancer invasion and/or metastasis.

PMID- 15573917
TI  - Mutation of beta-catenin does not coexist with K-ras mutation in colorectal
      tumorigenesis.
AB  - Alterations of the APC, K-ras, and beta-catenin genes are defined as early events
      in colorectal tumorigenesis. These alterations are well-known as constitutents of
      Vogelstein's pathway, however, the relationship among them is unclear. For
      understanding colorectal tumorigenesis it is important to evaluate their
      relationship. We analyzed the relationship between beta-catenin and K-ras gene
      mutations in clinical colorectal samples. Sixty-four cases of colorectal cancers
      (44 proximal, 20 distal) without a family history of colorectal cancer were used
      for this study. We purified genomic DNAs from fresh surgical samples and, thus,
      analyzed the mutations of beta-catenin (exon 3) and K-ras (codons 12 and 13) by
      PCR direct sequencing method using Big Dye terminator cycle sequencing with
      AmpliTaq polymerase FS. We found 27% (17/64) K-ras mutations (proximal 25%,
      11/44; distal 30%, 6/20). The frequency of beta-catenin mutations was 11% (7/64;
      proximal 9%, 4/44; distal 15%, 3/20). All cases with beta-catenin mutation had no
      mutation of K-ras. All sites of beta-catenin mutation have been reported
      previously (codons 33, 34, 41, 45). In cell lines, it has been reported
      previously that beta-catenin and K-ras play the same roles in activation of
      cyclin D1 transcription. Our results may support this report and suggest that
      some colorectal cancers with beta-catenin mutation will progress without K-ras
      mutation. Further study may disclose a new pathway or new mechanism of colorectal
      tumorigenesis.

PMID- 15573918
TI  - The effect of H2 antagonists on proliferation and apoptosis in human colorectal
      cancer cell lines.
AB  - Cimetidine is known to enhance the survival of gastro-intestinal cancer patients,
      though the mechanisms involved are incompletely understood. Postulated modes of
      action include blocking the proliferative effect of tumors and inhibiting T
      suppressor cell activity, both of which are thought to be mediated by histamine
      type 2 receptors. Apoptotic cell death may offer an alternative explanation for
      reduced cell growth. We aimed to examine the effects of histamine, cimetidine,
      and ranitidine on in vitro proliferation and apoptosis in two human colorectal
      cancer cell lines, Caco-2 and LoVo. A cell proliferation assay was used as an
      index of cell growth. Histamine receptor status was determined by quantifying
      cyclic adenosine monophosphate and apoptosis via DNA fragmentation. Results show
      that histamine (10(-5) to 10(-9) M) had no effect on the growth of either cell
      line. The proliferation of Caco-2 was inhibited by ranitidine (10(-7) M) alone
      and in combination with histamine. Cimetidine (10(-5) M) only suppressed the
      growth of Caco-2 in the presence of histamine. The H2 antagonists had no effect
      on LoVo irrespective of histamine. There was no accumulation of cyclic adenosine
      monophosphate in Caco-2 cells in response to histamine at a similar
      concentration. Apoptosis was induced in Caco-2 by both antisecretory drugs, and
      only ranitidine caused apoptotic cell death in LoVo cells. We conclude that
      cimetidine and ranitidine inhibit Caco-2 cancer cells in vitro, independently of
      the H2 receptor. In addition, both drugs induce apoptosis in the same cell line.
      Growth inhibition and apoptosis are likely to contribute to the tumor regressive
      properties of cimetidine and ranitidine in vivo.

PMID- 15573919
TI  - Premedication with tramadol in patients undergoing colonoscopy: a double-blind
      randomized placebo-controlled study.
AB  - Colonoscopy is often disturbed by poor patient tolerance; benzodiazepines or
      opiates are routinely used to overcome such problems, despite the possibility of
      undesired effects. Tramadol, an opiate analogue with potentially fewer side
      effects, has not been tested yet to this end. The aim of the study was therefore
      to evaluate the efficacy of tramadol as a premedication for the colonoscopic
      procedure. Fifty patients were randomly allocated to receive an i.v. infusion of
      100 ml saline, with 100 mg tramadol or alone, before endoscopy. At the end of the
      procedure patients were asked to score the discomfort experienced and to give an
      exam evaluation. The endoscopist also analyzed his performance. Tramadol patients
      reported a pain score of 39 +/- 10 (mean +/- SE), compared to 45 +/- 8 for the
      placebo group (P = 0.25); the evaluation of endoscopy was also similar (tramadol,
      66 +/- 12; placebo, 70 +/- 9; P = 0.15). The endoscopist also reported a similar
      score (65 +/- 4 after tramadol; 69 +/- 4 after placebo; P = 0.2). No significant
      sex- or age-related differences were detected. We conclude that tramadol, at
      least as a monotherapy, seems scarcely effective for controlling pain evoked by
      colonoscopy.

PMID- 15573920
TI  - Primary malignant melanoma of the esophagus: long-term survival following pre-
      and postoperative adjuvant hormone/chemotherapy.

PMID- 15573921
TI  - Persistent CEA elevation in a patient with psoriasis and a history of metastatic
      colorectal cancer with no evidence of residual tumor.

PMID- 15573922
TI  - RCAS1, a useful serum marker to predict the recurrence of cancer: two cases of
      cholangiocarcinoma and pancreatic cancer.

PMID- 15573923
TI  - Comparison of air-coupled balloon esophageal and anorectal manometry catheters
      with solid-state esophageal manometry and water-perfused anorectal manometry
      catheters.
AB  - Clinical gastrointestinal manometry studies are currently performed with
      multilumen water-perfused polyvinyl or strain gauge sensor solid-state catheters.
      A disposable catheter incorporating air-filled balloons has been developed with
      performance characteristics suitable for esophageal and anorectal manometry
      studies. Our aim was to compare esophageal and anorectal pressure measurements
      using this newly developed catheter with measurements obtained using standard
      solid-state or water-perfused catheters. Measurements of resting LES pressure,
      esophageal contraction amplitudes, and anorectal rest and squeeze pressures were
      obtained in 10 healthy volunteers using a solid-state esophageal catheter, a
      water-perfused anorectal catheter, and air-filled balloon esophageal and
      anorectal catheters. Correlation coefficient analysis demonstrated that LES
      pressures, esophageal contraction amplitudes, and anorectal resting and squeeze
      pressures were not significantly among between the different catheters. We
      conclude that recently developed air-filled balloon esophageal and anorectal
      manometry catheters provide very similar measurements of LES, esophageal body,
      and anorectal sphincter pressures compared to presently used manometry catheters.

PMID- 15573924
TI  - Taurodeoxycholate stimulates intestinal cell proliferation and protects against
      apoptotic cell death through activation of NF-kappaB.
AB  - We hypothesized that the NF-kappaB pathway would be operative in the
      proliferative effect of bile salts on enterocytes. To determine this, we studied
      the effect of the bile salt taurodeoxycholate on cultured rat enterocyte
      proliferation and apoptosis and examined the role of NF-kappaB activation in
      these growth regulatory processes. Intestinal epithelial cells were grown for 6
      days with or without taurodeoxycholate. Proliferation was measured. The cells
      were exposed to a known apoptotic stimulus, TNF-alpha and cyclohexamide.
      Apoptosis was quantified using cell number and the TUNEL stain. NF-kappaB
      activation was determined by an electrophoretic mobility shift assay. NF-kappaB
      activation was inhibited by an IkappaB superrepressor. Taurodeoxycholate
      stimulated cell proliferation (P < 0.01) and induced resistance to TNF-alpha
      induced apoptosis (P < 0.01). Taurodeoxycholate induced NF-kappaB activation.
      Inhibition of NF-kappaB prevented taurodeoxycholate-induced IEC-6 cell
      proliferation and rendered cells sensitive to TNF-alpha-induced apoptosis.
      Taurodeoxycholate stimulates intestinal epithelial cell proliferation and
      protects intestinal epithelial cells from TNF-alpha-induced apoptosis through NF
      kappaB. These data support an important beneficial role of bile salts in
      regulation of mucosal growth and repair. Decreased enterocyte exposure to luminal
      bile salts, as occurs during starvation and parenteral nutrition, may have a
      detrimental effect on mucosal integrity.

PMID- 15573925
TI  - Knowledge, quality of life, and use of complementary and alternative medicine and
      therapies in inflammatory bowel disease: a comparison of Chinese and Caucasian
      patients.
AB  - Inflammatory bowel disease is rare in the Chinese population, which may result in
      limited support, misinformation, and unalleviated fears and adversely affect
      quality of life (QOL). This study compared the inflammatory bowel disease (IBD)
      related knowledge, QOL, and use of complementary and alternative medicines and
      therapies (CAMT) in two contrasting IBD populations. Chinese and Caucasian IBD
      patients completed a questionnaire on IBD knowledge and CAMT usage. QOL was
      evaluated using the validated Inflammatory Bowel Disease Questionnaire. One
      hundred sixty-two IBD patients were recruited, 81 Chinese and 81 Caucasian. The
      IBD knowledge score was higher in Caucasian than in Chinese IBD patients (median
      difference, 6.5; P = 0.001) and was independent of education and occupation.
      Twenty-one-percent of Chinese subjects incorrectly identified their IBD type (0%
      in the Caucasian group; P < 0.001). QOL was higher in the Chinese than the
      Caucasian group, but not significantly different after adjusting for disease
      activity. QOL was unassociated with IBD knowledge. The overall use of CAMT was
      similar in both groups (33% of Chinese and 37% of Caucasian patients) and similar
      for Crohn's disease and ulcerative colitis. IBD-related knowledge was inferior in
      Chinese compared to Caucasian IBD patients. Health-related QOL is unlikely to be
      greatly influenced by disease-related knowledge or education. A high proportion
      of Chinese and Caucasian IBD patients uses CAMT.

PMID- 15573926
TI  - Inflammatory fibroid polyp of the small intestine causing intussusception: a
      report of two cases.

PMID- 15573927
TI  - Does serum hexosaminidase activity play a role in the diagnosis of strangulated
      bowel obstruction? An experimental study.
AB  - Strangulation is associated with an increased risk of mortality and morbidity in
      patients with mechanical bowel obstruction. The accurate and early recognition of
      the presence of strangulation is important to allow safe nonoperative treatment.
      A number of studies have shown that there was no single and reliable test to
      detect or exclude the presence of strangulation. The aim of this study was to
      evaluate the role of serum hexosaminidase (Hex) levels in recognition of
      strangulation in an experimental model of closed loop small bowel obstruction.
      Forty-two Wistar albino rats were divided into four groups: I, control (n = 5);
      II, sham laparotomy (n = 5); III, simple obstruction (n = 16); and IV,
      strangulation groups (n = 16). Activity levels of total Hex and its fractions
      (Hex A and B) were assayed in serum samples obtained from rats after 3 and 8 hr.
      Samples of small bowel were also evaluated histologically. Histological
      evaluation of bowel sections obtained from the strangulation group after 8 hr,
      revealed transmural hemorrhagic infarction in all animals with a mean +/- SD
      total Hex activity of 978.25 +/- 150 nmol/hr/ml, which was significantly higher
      than that in the other groups (P < 0.001). Although sections of bowel from the
      strangulation group after 3 hr showed severe ischemic injury, the activities of
      total Hex, Hex A, and Hex B were not different from those of the control, sham,
      and simple obstruction groups. Histological examination of these groups did not
      show any sign of ischemia. Total Hex, Hex A, and Hex B activities in the
      strangulation group were all significantly greater than the activities seen in
      the simple obstruction group (P < 0.001, for all). In conclusion, increased serum
      hex levels indicate irreversible transmural infarction only in the late period of
      strangulation in the closed loop small bowel obstruction model. It seems unuseful
      for detecting reversible and/or irreversible ischemia in the early period of
      strangulation.

PMID- 15573928
TI  - Bowel obstruction secondary to idiopathic adhesions.

PMID- 15573929
TI  - Plasma GLP-2 levels and intestinal markers in the juvenile pig during intestinal
      adaptation: effects of different diet regimens.
AB  - Adaptation of the residual small bowel following resection is dependent on
      luminal and humoral factors. We aimed to establish if circulating levels of
      glucagon-like peptide (GLP-2) change under different dietary regimens following
      resection and to determine if there is a relationship between plasma GLP-2 levels
      and markers of intestinal adaptation. Four-week-old piglets underwent a 75%
      proximal small bowel resection (n = 31) or transection (n = 14). Postoperatively
      they received either pig chow (n = 14), nonpolymeric (elemental) infant formula
      (n = 7), or polymeric infant formula alone (n = 8) or supplemented either with
      fiber (n = 6) or with bovine colostrum protein concentrate (CPC; n = 10) for 8
      weeks until sacrifice. Plasma GLP-2 levels were measured at weeks 0, 2, 4, and 8
      postoperatively. In addition, end-stage parameters were studied at week 8
      including weight gain, ileal villus height, crypt depth, and disaccharidase
      levels. Plasma GLP-2 levels were higher in resected animals compared to
      transected animals fed the same diet. Plasma GLP-2 levels were significantly
      increased in the colostrum protein isolate-supplemented animals following
      resection compared to all other diet groups. The increase in plasma GLP-2 (pM)
      was greatest in the first 2 weeks postresection (week 0, 15.5; week 2, 30.9),
      followed by a plateau at weeks 2 to 4 and a decrease in GLP-2 levels from week 4
      to week 8. At week 8, no relationships were found between the plasma GLP-2 levels
      and the measurements of weight gain, villus height, lactase, sucrase, maltase,
      crypt depth, or villus/crypt ratio. Plasma GLP-2 levels increase in the first
      weeks following massive small intestinal resection. The increase in plasma GLP-2
      levels was enhanced by supplementation of the diet with CPC. The changes in GLP-2
      levels observed in this study may suggest that GLP-2 plays a role in the adaptive
      response in the intestine following resection in this preclinical model.

PMID- 15573930
TI  - Protective effect of lafutidine, a novel histamine H2-receptor antagonist, on
      dextran sulfate sodium-induced colonic inflammation through capsaicin-sensitive
      afferent neurons in rats.
AB  - Lafutidine, a histamine H2-receptor antagonist, exhibits gastric mucosal
      protective action mediated by capsaicin-sensitive afferent neurons, in addition
      to a potent antisecretory effect. In this study we examined the effect of
      lafutidine on dextran sulfate Na (DSS)-induced ulcerative colitis in rats, in
      relation to capsaicin-sensitive afferent neurons. Experimental colitis was
      induced in rats by daily treatment with 3% DSS in drinking water for 7 days.
      Lafutidine, capsaicin, and cimetidine were administered per os twice daily for 6
      days. The ulceration area, colon length, and myeloperoxidase (MPO) activity were
      measured on day 7 after the onset of DSS treatment. DSS caused severe mucosal
      lesions in the colon, accompanied by an increase in MPO activity as well as a
      decrease in body weight gain and colon length. Daily administration of lafutidine
      dose-dependently reduced the severity of DSS-induced colitis and significantly
      mitigated changes in the colon length and MPO activity. The effects of lafutidine
      were mimicked by daily administration of capsaicin but not cimetidine and were
      totally abolished by chemical ablation of capsaicin-sensitive afferent neurons.
      In contrast, desensitization of afferent neurons significantly worsened the
      colonic inflammation induced by DSS. It was also found that both lafutidine and
      capsaicin increased the secretion of mucus in the colonic mucosa. These results
      suggest that lafutidine is effective against the ulcerative colitis induced by
      DSS through capsaicin-sensitive afferent neurons. This action might be
      attributable at least partly to the enhancement of colonic mucus secretion.

PMID- 15573931
TI  - Prophylactic administration of topical glutamine enhances the capability of the
      rat colon to resist inflammatory damage.
AB  - Glutamine is an important nutrient for the GI tract and has been shown to exert a
      protective effect on the bowel. Nonetheless, in the context of IBD, data
      demonstrating a therapeutic role for glutamine has been inconclusive. IBD is
      associated with oxidative stress caused by reactive oxygen species. We aimed to
      investigate the effect of topical glutamine administration in rats before or
      after induction of colitis by trinitrobenzenosulfonic acid. In study I glutamine
      enemas were given beginning 2 days before or on the same day of induction of
      colitis. Inflammation severity was assessed by macroscopic and microscopic score
      and tissue myeloperoxidase activity. In study II glutamine enemas were given for
      3 days without induction of colitis: mitotic index and colonic crypt length were
      measured, as well as water-soluble low molecular weight antioxidants and energy
      rich phosphate levels (by HPLC). Results showed that glutamine significantly
      decreased indexes of inflammation when administered before induction of colitis.
      Glutamine caused an increase in the mitotic index and the levels of water-soluble
      low molecular weight antioxidants and energy-rich phosphates. We conclude that
      glutamine exerts a beneficial effect only when administered before induction of
      colitis, by increasing the resistance of the colonic tissue to inflammatory
      injury. This effect is probably mediated by increasing the antioxidant capacity
      and energy level of the tissue.

PMID- 15573932
TI  - Stress increases susceptibility to oxidative/nitrosative mucosal damage in an
      experimental model of colitis in rats.
AB  - Inflammatory bowel diseases (IBDs) are multifactorial processes. Clinical and
      animal studies indicate that emotional stress may contribute to the onset and
      progress of these diseases. On the other hand, enhanced free radical production
      in mucosal cells has been also implicated in the pathogenesis of IBD. Using an
      experimental model of colitis induced by intrarectal instillation of 2,4,6
      trinitrobenzene sulfonic acid (TNBS) plus ethanol (vehicle), we sought to
      determine whether prior exposure to immobilization stress modifies the
      susceptibility to oxidative damage in colonic mucosa. Several groups of Wistar
      rats were used: control (C) and stressed (by immobilization of 6 hr every day
      during 10 days; S) groups and rats receiving a colitis-inducing dose of TNBS on
      day 5 (30 mg; TNBS30) and a noninflammatory dose of TNBS on day 5 (5 mg; TNBS5)
      with or without stress (prior exposure, days 0-5, and after, days 5-10). At the
      10th day, colonic tissue was dissected and processed for biochemical studies.
      TNBS30 led to body weight loss, macroscopic colonic ulceration, and inflammation
      (determined by histological parameters and myeloperoxidase [MPO] activity) and to
      an increase in inducible nitric oxide synthase (NOS-2) activity and expression.
      TNBS5-instilled animals' body weight and biochemical inflammatory parameters were
      not significantly different from those in control animals. Interestingly, while
      stress did not modify body weight, macroscopic aspect of the mucosa, or NOS
      activity in animals receiving TNBS30, immobilization increased body weight loss,
      MPO levels, and malondialdehyde (MDA; an indicator of lipid peroxidation) levels
      after TNBS5. On the other hand, stress increased NOS-2 activity and
      immunohistochemical expression after instillation of TNBS5. Moreover,
      constitutive, Ca2+ -dependent NOS activity decreased in stressed animals
      instilled with TNBS5 compared with nonstressed animals receiving TNBS5 (-28.5 +/-
      6.6%; P < 0.05). These findings indicate that previous exposure to stressful
      stimuli is a factor in susceptibility to oxidative damage in experimental colitis
      and support a possible protective effect of treatment of stress before and during
      the development of inflammation in the colon.

PMID- 15573933
TI  - Henoch-Schonlein purpura presenting with ileal involvement in an adult.

PMID- 15573934
TI  - Colitic cancer developed after introduction of azathioprine.

PMID- 15573935
TI  - Avian influenza, Thailand.

PMID- 15573936
TI  - Tenth informal consultation on the global polio laboratory network, 6-8 September
      2004.

PMID- 15573937
TI  - Food safety regulators meet in Bangkok, Thailand.

PMID- 15573938
TI  - Influenza in the world.

PMID- 15573939
TI  - Fifth meeting of the Steering Committee on Immunization Safety.

PMID- 15573940
TI  - Sampling and interpolation of the a-wave of the electroretinogram.
AB  - This study was undertaken (a) to determine the minimum sampling frequency
      required to record a-waves evoked by flashes of very high energy without
      significant distortion and (b) to demonstrate that data sampled at a minimally
      adequate frequency can be interpolated to reconstruct the original waveform.
      METHODS: Dark-adapted ERGs from two anaesthetized macaque monkeys and an adult
      human were studied. Responses evoked by high-energy flashes that produced a-waves
      peaking as early as 5 or 6 ms after the flash were sampled at 5 kHz and
      transformed to obtain their discrete Fourier spectra. The amplitude of all
      spectral components above some cut-off frequency (e.g., 400 Hz) was then set to
      zero and the modified spectra transformed back into the time domain. The
      resulting computed responses, which contained no Fourier components above the cut
      off frequency, were compared with the original recorded samples. To assess the
      validity of one method of interpolation, sample sets consisting of every fifth
      point of records sampled at 5 kHz (i.e., sets of 1 kHz samples) were subjected to
      Fourier transformation to give spectra with a frequency range of 0-500 Hz. These
      spectra were extended from 500 Hz up to a much higher frequency (e.g., 8 kHz) by
      adding zeros. The extended spectra were transformed back into the time domain to
      provide sets of interpolated samples at twice the chosen spectral frequency limit
      (i.e., 16 kHz). RESULTS: Removing all Fourier components above 400 or 500 Hz had
      no significant effect upon the leading edge or peak of the a-wave. However,
      removing Fourier components above 500 Hz gave rise to slight distortion of the
      oscillatory potentials (OPs) that appeared just after the a-wave peak on the
      leading edge of the b-wave. Except for this small distortion, the original 5 kHz
      data samples corresponded very well with the interpolated curves that had been
      generated as described above from a 1 kHz subset of the samples. This provides
      further confirmation that dark-adapted ERG a-waves evoked by flashes of up to
      about 50,000 sc. Td sc do not contain Fourier components with frequencies above
      500 Hz. CONCLUSION: Human and macaque a-waves are completely represented by 1 kHz
      samples and Fourier methods can be used to reconstruct the original continuous
      waveform. However, to capture the OPs with complete fidelity, a higher sampling
      rate is necessary.

PMID- 15573941
TI  - Improved contact lens electrode for corneal ERG recordings in mice.
AB  - The electroretinogram (ERG) is routinely used to study retinal physiology in the
      clinic and in research. Due to their outstanding properties, contact lens
      electrodes (CLEs) are widely used for ERG recordings. Though the procedures for
      ERG recordings in mice are similar to those used in humans and larger
      vertebrates, use of CLEs in the mouse has been limited because of difficulties
      involved with the manufacturing of small contact lenses. We describe a simple
      instrument and method for manufacturing contact lenses and CLEs for stable ERG
      recordings in mice. The instrument operates like a hole-punch and is based on
      slip joint pliers incorporating a ball bearing on one jaw and forming plate on
      the other. These CLEs are simple to manufacture, inexpensive and provide stable,
      long-term recordings of corneal ERGs in mice. With minor modifications, these
      CLEs could be made for other small animals such as rats or fish.

PMID- 15573942
TI  - The effects of ageing on stereopsis. A VEP study.
AB  - Differences in brain activation between young (n = 11, ages 21-35) and elderly (n
      = 8, ages 70-84) healthy participants were studied using visual evoked potentials
      (VEPs) to different kinds of computer generated random-dot patterns. The main
      stimulus of interest was a 2 x 2 array of rectangles whose rectangles moved to
      and fro in depth. Control conditions were similar 2 x 2 arrays, one with side-to
      side lateral motion (LM) of the rectangles, and one a stationary baseline
      condition. The third non-stereo stimulus was an expanding field of small dots in
      radial motion (RM). Significant stereo related activation was found in both age
      groups. The stereo VEPs showed a longer latency of depth reversal triggered VEP
      peaks compared to control LM VEPs. The amplitudes of LM VEPs were larger than the
      baseline VEPs. Age-related differences were found not only in stereo but also in
      the other conditions. Thus the latency of early VEP peaks was shorter and their
      amplitude higher in the elderly for LM and baseline conditions, and the younger
      participants showed significantly higher activation in the later VEP peaks of all
      conditions. Our main finding is no evidence for age related stereo specific
      effects in brain activation, but instead more general and subtle changes that
      affect widely different visual stimulus conditions.

PMID- 15573943
TI  - Assessing macular pigment from SLO images.
AB  - PURPOSE: To assess the spectral characteristics and spatial distribution of
      macular pigment by comparing relative retinal reflectance at four different
      wavelengths. METHODS: A Rodenstock scanning laser opththalmoscope (SLO) with four
      spectral beams, 488, 544, 633 and 780 nm, was used to obtain images of the normal
      macula from five eyes of three normal subjects. The relative spectral reflectance
      was determined along a horizontal path extending from nasal to temporal retina
      through the fovea for each image. A comparison of this data provided an
      indication of the relative density and the actual spatial extent of macular
      pigmentation. RESULTS: There is an area of hyper-pigmentation obtained from
      averaging the data from all five eyes that extends from about 6 deg symmetrically
      into nasal and temporal macula surrounding a small zone of greater hyper
      pigmentation that extends about 3 deg on each side of the fovea. The smaller
      central zone has a relatively high absorption for blue light and is considered to
      represent macular pigment. The larger less hyper-pigmented zone is considered to
      represent melanin in the retinal pigment epithelium. CONCLUSION: The circularly
      symmetrical hyper-pigmented central macula including the yellow macular pigment
      can be assessed by comparing different spectral images obtained from an SLO.

PMID- 15573944
TI  - Assessing diabetic retinopathy using two-field digital photography and the
      influence of JPEG-compression.
AB  - OBJECTIVE: To study the effectiveness of two digital 50 degree photographic
      fields per eye, stored compressed or integrally, in the grading of diabetic
      retinopathy, in comparison to 35-mm colour slides. SUBJECTS AND METHODS: Two
      field digital non-stereoscopic retinal photographs and two-field 35-mm retinal
      photographs were made at the same time from patients visiting a diabetic
      retinopathy outpatient clinic. The digital images were stored integrally (TIFF
      file) and in a compressed way (JPEG-file). Two ophthalmologists assessed the
      photographs in a masked fashion. The results were compared. The sensitivity and
      specificity for the detection of vision-threatening diabetic retinopathy were
      calculated, using only the grading of the most affected eye. The differences
      between the retinopathy gradings of the two kinds of photographs were analysed.
      RESULTS: The agreement for the grading of DR compared to slides was good, both
      for the compressed and for the integrally stored images (kappa 0.63-0.68). The
      sensitivity for the detection of vision-threatening diabetic retinopathy using
      the JPEG-stored images was 0.72-0.74, specificity 0.93-0.98. The sensitivity for
      vision-threatening retinopathy detection using the integrally stored images was
      0.86-0.92, specificity 0.93. CONCLUSIONS: Two-field digital retinal photography
      is effective in diabetic retinopathy grading and it can replace 35-mm retinal
      photography. Vision-threatening retinopathy can be detected on the images with
      reasonable to good sensitivity and specificity. An experienced grader should
      assess the images. The compression of the digital images seems to have some
      adverse effect on the detection of diabetic retinopathy.

PMID- 15573945
TI  - Increasing the sensitivity of the multifocal visual evoked potential (mfVEP)
      technique: incorporating information from higher order kernels using a principal
      component analysis method.
AB  - Principal component analysis (PCA) was employed to enhance the multifocal visual
      evoked potential (mfVEP) technique. First, by using four principal components,
      the separation of mfVEP signals from noises was improved. Second, two otherwise
      unused higher order kernels, the 2nd slice of the 2nd order kernel and the 4th
      order kernels, were utilized by combining information obtained from the PCA. The
      PCA-kernel method improves the efficiency of the mfVEP test. The false positive
      rate, based upon an analysis of a noise window, was decreased by a factor of
      about one-third and the improvement in sensitivity of detecting glaucomatous
      defects was nearly as good as a doubling of the recording time.

PMID- 15573946
TI  - Comparison of mfERG waveform components and implicit time measurement techniques
      for detecting functional change in early diabetic eye disease.
AB  - This study first compares two methods for measuring first order multifocal
      electroretinogram (mfERG) implicit time abnormalities in eyes with early diabetic
      retinopathy. Two analysis methods are used: template stretching (multiplicative
      scaling) of an 80 msec response epoch and template sliding (cross-correlation or
      additive scaling) of portions of responses containing the major waveform
      features. The study also compares the relative sensitivities of N1, P1 and N2
      implicit time assessed by cross-correlation. The nature of the change in the
      mfERG waveform associated with diabetes is also assessed. MfERGs were recorded
      from 15 eyes of 15 individuals with diabetes and early non-proliferative
      retinopathy and 20 eyes of 20 healthy control subjects of similar age. Implicit
      time determined by template stretching is more frequently abnormal in the eyes of
      the diabetic subjects than the implicit time of any of the components assessed by
      template sliding. This is attributable to the lower variability of the template
      stretching implicit time measure in normals. Of the components, P1 is most often
      abnormal in the eyes of individuals with diabetes. Responses recorded from
      retinal areas with retinopathic signs are more often abnormal than those from
      other areas. Later components of the response are not delayed more than earlier
      ones. We conclude that template stretching is a sensitive measurement technique,
      but that it does not fully capture the effect of diabetes on the first order
      mfERG well.

PMID- 15573947
TI  - Inner retinal contributions to the multifocal electroretinogram: patients with
      Leber's hereditary optic neuropathy (LHON). Multifocal ERG in patients with LHON.
AB  - In this study we examine the multifocal electroretinogram (mfERG) recorded from
      patients suffering from Leber's hereditary optic neuropathy (LHON), a
      degeneration of the ganglion cell and nerve fibre layers of the retina. We
      compared the mfERGs recorded from 11 patients with LHON, to those from 11 control
      subjects. The pattern ERG (PERG) was additionally performed with 9 of the
      patients. MfERGs were recorded and analysed using the VERIS 3.01 system with a
      stimulus of 103 equal-sized hexagons. For analysis, hexagons were grouped
      according to distance from the optic nerve head (ONH) and according to distance
      from the fovea. Two significant differences were found between the waveforms of
      the two groups: In the first order kernel, the control group showed a component
      around 34 ms that decreased with distance from the ONH. This component was
      reduced in the LHON group of subjects. In the second order (first slice) kernel,
      the patient group was missing features that decrease with distance from the fovea
      in the control group. PERG amplitudes showed a significant correlation with the
      amplitude of the second order mfERG kernel. The results show that the damage to
      ganglion cells and nerve fibres caused by LHON can be detected in mfERG
      recordings and indicate that activity from the inner retina can contribute
      significantly to first and second order waveforms.

PMID- 15573948
TI  - Spinocerebellar degeneration with negative electroretinogram: dysfunction of the
      bipolar cells.
AB  - We report the characteristics of three patients with spinocerebellar degeneration
      (SCD) with negative-type electroretinograms (ERGs). None of the patients showed
      retinal degeneration, but all had severe cerebellar ataxia, and brain MRIs showed
      cerebellar atrophy. Negative-type ERGs have been implicated in the selective
      functional impairment of the inner retinal layer, but few studies have reported
      dysfunction of the inner nuclear layer in SCD patients. Our subjects may be the
      first reported SCD cases with negative-type ERGs. Our results suggest that an
      etiologic relationship exists between cerebellar ataxia and negative-type ERGs.
      Further investigation of ERGs in patients with SCD could potentially lead to the
      identification of an increased number of SCD patients with negative-type ERGs and
      retinal pathogenesis.

PMID- 15573949
TI  - Acute retinal toxicity from the novel anti-tumor agent, Irofulven.

PMID- 15573950
TI  - Relationships between the plasma concentrations of insulin-like growth factor-I
      in dairy cows and their fertility and milk yield.
AB  - The relationships between insulin-like growth factor-I (IGF-I) and the fertility
      and milk yield of Holstein-Friesian dairy cows were investigated. The
      concentration of IGF-I in blood was measured weekly from one week before to 12
      weeks after calving in 177 multiparous cows and at four times during this period
      in 142 primiparous cows; the concentration of IGF-I in milk was measured in 50 of
      the multiparous cows. The plasma concentrations of IGF-I were higher in the
      primiparous than in the multiparous animals. In the primiparous cows, high
      concentrations of IGF-I before calving were associated with longer calving to
      conception intervals. Conversely, in the multiparous cows low concentrations of
      IGF-I before and after calving were associated with a failure to conceive,
      despite repeated services. Multiparous cows with IGF-I concentrations of greater
      than 25 ng/ml in the week after calving were 11 times more likely to conceive to
      first service than those with lower concentrations. Concentrations of IGF-I
      greater than 50 ng/ml at first service increased the likelihood of conception
      five-fold. Cows with higher peak milk yields had lower plasma concentrations of
      IGF-I and took longer to return to ovarian cyclicity. The negative relationship
      between milk yield and return to cyclicity was stronger in the multiparous cows
      (P < 0.002) than in the primiparous cows (P < 0.04). The concentrations of IGF-I
      in milk followed a different pattern and were not associated with the changes in
      plasma IGF-I or fertility.

PMID- 15573951
TI  - Possible interaction between myxomatosis and calicivirosis related to rabbit
      haemorrhagic disease affecting the European rabbit.
AB  - Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD
      like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996
      and 1997 in two areas of France were analysed. For each disease, the effects of
      bodyweight, year, month and seropositivity for the other disease were modelled by
      using logistic regressions. In one area, a model including RHD seropositivity was
      selected to explain the myxoma virus seropositivity. Models including myxoma
      virus seropositivity were selected to explain the RHD seropositivity in both
      areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and
      8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and
      seropositive to RHD. The year and bodyweight had significant effects for
      myxomatosis in one area and for RHD in both areas.

PMID- 15573952
TI  - Diagnostic investigation into the role of Chlamydiae in cases of increased rates
      of return to oestrus in pigs.
AB  - Cervical swabs and serum samples were taken from Swiss herds of sows with high
      rates of irregular return to oestrus (group A) and from control herds without
      reproductive problems (group B. The genital tracts of 21 slaughtered sows of
      group A were also examined. The swabs and genital tracts were screened for
      Chlamydiae by a new 16S rRNA PCR and the sera by an ELISA for Chlamydiaceae
      lipopolysaccharide. Chlamydophila (Cp) abortus was isolated from seven of the 65
      swabs taken from group A but from none of the 128 swabs taken from group B.
      Chlamydia suis was present in swabs from both groups A (1.5 per cent) and B (2.3
      per cent). In addition, Cp abortus was detected in 33.3 per cent of the genital
      tracts. Of the 193 sera tested, 61.7 per cent were positive, with no significant
      difference between group A (52.3 per cent) and group B (66.4 per cent). Chlamydia
      like organisms were detected in 28.2 per cent of the swabs from group A and in 22
      per cent of those from group B.

PMID- 15573953
TI  - Distribution of PCV-2 DNA in the reproductive tract, oocytes and embryos of PCV-2
      antibody-positive pigs.

PMID- 15573954
TI  - Simple procedure for emptying long-term ovarian cysts in cattle.

PMID- 15573955
TI  - Identification of a European bat lyssavirus type 2 in a Daubenton's bat found in
      Lancashire.

PMID- 15573956
TI  - Badgers and bovine TB.

PMID- 15573957
TI  - Badgers and bovine TB.

PMID- 15573958
TI  - Remuneration for TB testing.

PMID- 15573959
TI  - Badgers and hedgehogs.

PMID- 15573960
TI  - Early language development in children with a genetic risk of dyslexia.
AB  - We report on a prospective longitudinal research programme exploring the
      connection between language acquisition deficits and dyslexia. The language
      development profile of children at-risk for dyslexia is compared to that of age
      matched controls as well as of children who have been diagnosed with specific
      language impairment (SLI). The experiments described concern the perception and
      production of grammatical morphology, categorical perception of speech sounds,
      phonological processing (non-word repetition), mispronunciation detection, and
      rhyme detection. The results of each of these indicate that the at-risk children
      as a group underperform in comparison to the controls, and that, in most cases,
      they approach the SLI group. It can be concluded that dyslexia most likely has
      precursors in language development, also in domains other than those
      traditionally considered conditional for the acquisition of literacy skills. The
      dyslexia-SLI connection awaits further, particularly qualitative, analyses.

PMID- 15573961
TI  - Deficits in dyslexia: barking up the wrong tree?
AB  - Reviews of the dyslexia literature often seem to suggest that children with
      dyslexia perform at a lower level on almost any task. Richards et al. (Dyslexia
      2002; 8: 1-8) note the importance of being able to demonstrate dissociations
      between tasks. However, increasingly elegant experiments, in which dissociations
      are found, almost inevitably find that the performance of children with dyslexia
      is lower as tasks become more difficult! By looking for deficits in dyslexia,
      could we be barking up the wrong tree? A methodological approach for
      circumventing this potential problem is discussed.

PMID- 15573962
TI  - Time reproduction in finger tapping tasks by children with attention-deficit
      hyperactivity disorder and/or dyslexia.
AB  - AIM: Deficits in timing and sequencing behaviour in children with dyslexia and
      with attention-deficit hyperactivity disorder have already been identified.
      However many studies have not controlled for comorbidity between dyslexia and
      ADHD. This study investigated timing performance of children with either dyslexia
      or ADHD, or ADHD + dyslexia or unaffected children using a finger tapping
      paradigm. METHOD: Four groups of children (ADHD x Dyslexia) with a total of 68
      children were compared using a four factorial design with two between-subject
      factors (ADHD (yes/no), dyslexia (yes/no)) and two within-subject factors, inter
      stimulus interval (263, 500, 625, 750, 875 and 1000 ms) and tapping condition
      (free tapping, synchronous tapping, and unpaced tapping). In addition the
      complexity of rhythm reproduction pattern (unpaced tapping) was varied
      (simple/complex). RESULTS: No significant differences were found either in the
      ability of the ADHD or the dyslexia groups to sustain a self-chosen free tapping
      rate or to generate a stable inter-response interval either by synchronising to a
      signal or in reproducing a given interval without the previous pacing signal.
      Response averages showed the expected asynchrony and variability. In rhythm
      pattern reproduction the groups did not differ significantly in their ability to
      reproduce rhythms. However, a significant two way interaction effect between
      dyslexia and complexity was apparent indicating that the difference in levels of
      performance for simple versus complex rhythms was more pronounced for dyslexia
      than for the two other groups. CONCLUSION: The results indicate that motor timing
      ability in the millisecond range below 1000 ms in children with ADHD and/or
      dyslexia is intact. The performance of the comorbid group was revealed to be
      similar to the performance of the single disorder groups, but both the dyslexic
      groups were relatively worse than either the ADHD-only or the unimpaired group at
      reproducing complex versus simple rhythms.

PMID- 15573963
TI  - Prevalence of persistent primary reflexes and motor problems in children with
      reading difficulties.
AB  - It has been shown that some children with reading difficulties have underlying
      developmental delay and that this may be related to the persistence of primary
      reflexes. This study investigated the prevalence of persistent primary reflexes
      in the ordinary primary school population and how this related to other cognitive
      and social factors. Three groups of 41 children were drawn from a representative,
      cross-sectional sample of 409 children (aged 9-10 years) attending 11 ordinary
      primary schools in N. Ireland. The three groups represented the bottom, middle
      and top 10% respectively of readers from the total sample population. The
      relative persistence (on a scale of 0 to 4) of the Asymmetrical Tonic Neck Reflex
      (ATNR) and the prevalence of motor difficulties were assessed for these 3 groups.
      The role of 5 predictor variables (verbal IQ, social deprivation, sex, month of
      birth and religious affiliation) in determining the reading level of the total
      sample was also investigated. It was found that the lowest reading group had a
      significantly higher mean level of ATNR (1.56 [95% CI 1.22-1.90]) compared with
      the middle reading group (0.56 [0.22-0.90]) and the top reading group (0.59 [0.25
      0.92]). 17% of children in the lowest reading group had extremely high levels of
      the ATNR while 24% showed no presence of ATNR. This contrasted with 0% and 66%,
      respectively for both middle and top reading groups. It was also found that there
      was a significant difference between the lowest reading group and the top reading
      group on a standardised test of motor ability. Furthermore, there was evidence
      that ATNR persistence but not motor ability was associated with the sex of the
      child with boys, in particular, at risk. There was no evidence that ATNR
      persistence or motor ability was significantly associated with social
      deprivation. It was also found that there were no significant differences between
      dyslexic and non-dyslexic children with reading difficulties in motor (including
      balance) performance. This study highlights the high levels of primary reflex
      persistence in children with reading difficulties and it provides further
      evidence of the association between reading difficulties and movement
      difficulties in young children. However, while the implications for intervention
      are discussed, it is stressed that the persistence of primary reflexes cannot be
      used as a causal model for reading difficulties, including dyslexia.

PMID- 15573964
TI  - The cognitive deficits responsible for developmental dyslexia: review of evidence
      for a selective visual attentional disorder.
AB  - There is strong converging evidence suggesting that developmental dyslexia stems
      from a phonological processing deficit. However, this hypothesis has been
      challenged by the widely admitted heterogeneity of the dyslexic population, and
      by several reports of dyslexic individuals with no apparent phonological deficit.
      In this paper, we discuss the hypothesis that a phonological deficit may not be
      the only core deficit in developmental dyslexia and critically examine several
      alternative proposals. To establish that a given cognitive deficit is causally
      related to dyslexia, at least two conditions need to be fulfilled. First, the
      hypothesized deficit needs to be associated with developmental dyslexia
      independently of additional phonological deficits. Second, the hypothesized
      deficit must predict reading ability, on both empirical and theoretical grounds.
      While most current hypotheses fail to fulfil these criteria, we argue that the
      visual attentional deficit hypothesis does. Recent studies providing evidence for
      the independence of phonological and visual attentional deficits in developmental
      dyslexia are reviewed together with empirical data showing that phonological and
      visual attentional processing skills contribute independently to reading
      performance. A theoretical model of reading is outlined in support of a causal
      link between a visual attentional disorder and a failure in reading acquisition.

PMID- 15573966
TI  - Getting into print--some suggestions.

PMID- 15573965
TI  - Reading comprehension and reading related abilities in adolescents with reading
      disabilities and attention-deficit/hyperactivity disorder.
AB  - Reading comprehension is a very complex task that requires different cognitive
      processes and reading abilities over the life span. There are fewer studies of
      reading comprehension relative to investigations of word reading abilities.
      Reading comprehension difficulties, however, have been identified in two common
      and frequently overlapping childhood disorders: reading disability (RD) and
      attention-deficit/hyperactivity disorder (ADHD). The nature of reading
      comprehension difficulties in these groups remains unclear. The performance of
      four groups of adolescents (RD, ADHD, comorbid ADHD and RD, and normal controls)
      was compared on reading comprehension tasks as well as on reading rate and
      accuracy tasks. Adolescents with RD showed difficulties across most reading
      tasks, although their comprehension scores were average. Adolescents with ADHD
      exhibited adequate single word reading abilities. Subtle difficulties were
      observed, however, on measures of text reading rate and accuracy as well as on
      silent reading comprehension, but scores remained in the average range. The
      comorbid group demonstrated similar difficulties to the RD group on word reading
      accuracy and on reading rate but experienced problems on only silent reading
      comprehension. Implications for reading interventions are outlined, as well as
      the clinical relevance for diagnosis.

PMID- 15573967
TI  - Certifying and investigating deaths: the need for reform. 1. The shipman inquiry
      death certification.

PMID- 15573968
TI  - Certifying and investigating deaths: the need for reform. 2. Death certification
      and the coroner service.

PMID- 15573969
TI  - Suicide by gunshot in the United Kingdom: a review of the literature.
AB  - This paper reviews the research literature on gunshot suicide in the United
      Kingdom and the international literature with reference to strategies aimed at
      preventing gunshot suicides. Trends in gun ownership and changes in firearm
      legislation in the UK over the past 20 years are described. Most UK gunshot
      suicides are male, middle-aged and living with a partner and involve the use of
      shotguns. They are less likely to have current or past mental health problems, or
      a previous act of self-harm, than people who commit suicide by other methods, and
      their suicide is more likely to have been precipitated by a relationship dispute.
      Where alcohol is consumed the amount tends to be large. The international
      literature provides evidence of a strong association between rates of gun
      ownership and gunshot suicide, and some evidence of a reduction in firearm
      suicide rates following the introduction of restrictive firearm legislation. Over
      the past 20 years the number of gunshot suicides in the UK has declined by over
      50% to a little over a hundred deaths per annum. At the same time, firearm
      legislation has become progressively more restrictive and rates of gun ownership
      have declined. Measures, which might further reduce the prevalence of gunshot
      suicides in the UK, are discussed.

PMID- 15573970
TI  - Neonaticidal mothers: are more boys killed?
AB  - Neonaticide refers to the homicide of a newborn of less than 24 hours old.
      Recently, certain authors have reported that only boys were victims (Dube, 1998;
      Haapasalo and Petaja, 1999). The aim of this study was to determine whether the
      proportion of male/female victims identified in the literature varied
      significantly from the official proportions of males/females at birth in
      countries of the Western World. Two types of study were taken into account to
      identify the victims' sex, namely, those presenting case reports and those
      presenting case series. A total of 420 neonaticides were included in our
      analyses. The majority of newborn victims were male (58.3%). However, there was
      no significant difference compared with the percentage of male births (51.4%).
      Based on the data collected, results indicate overall that a child's sex is not a
      significant factor associated with neonaticide.

PMID- 15573971
TI  - The detection and treatment of substance abuse in offenders with major mental
      illness: an intervention study.
AB  - Previous research demonstrated that alcohol and drug misuse prior to admission to
      special (high and medium) security psychiatric care in Scotland was high.
      Evidence from clinical practice subsequently suggested that the situation was
      worsening. In response, a three-pronged strategy was implemented: staff were
      trained in alcohol and drug issues in mentally disordered offenders, an admission
      screening programme was introduced to detect those at risk, and specific
      interventions were developed. This paper presents data on the admission screening
      programme and on a specific intervention. Study 1 describes the admission data on
      86 male patients admitted to the State Hospital, Carstairs. It confirmed that
      alcohol (81%) and drug (75%) misuse were rising in this population. Combined drug
      and alcohol abuse was common resulting in the development of joint treatment
      interventions. Study 2 describes an eight-week drug and alcohol education and
      awareness programme. An evaluation of this intervention showed that subjects'
      knowledge of alcohol and drug issues rose significantly pre to post-intervention.
      However no difference was found in the stage of change or locus of control
      measures. A number of possible explanations for this finding are discussed,
      including the validity of the instruments and the effect of detainment in a high
      security psychiatric environment on the opportunity to change. In spite of the
      limitations of the environment, the prevalence of alcohol and drug misuse and its
      association with violence emphasise the need for specific programmes.

PMID- 15573972
TI  - 'Here There Be Monsters': the public's perception of paedophiles with particular
      reference to Belfast and Leicester.
AB  - This research study sought to investigate the public perception of paedophiles.
      It was undertaken in Belfast (Northern Ireland) and Leicester (England) in an
      attempt to determine whether or not regional variations existed in relation to
      the public's perception of paedophiles. In doing this, the study sought to test
      four hypotheses; (1) That the press affects the public's perception of
      paedophiles; (2) that the public's perception of paedophiles is not congruent
      with legal and clinical definitions; (3) that the Sarah Payne case has helped to
      reinforce the public's perception of a predatory paedophile; and (4) that the
      public's perception is based on fear and irrationality. These hypotheses were
      tested via the distribution of a questionnaire to an opportunistic sample on the
      streets of Belfast and Leicester. Although the results did not support the
      hypotheses, they did yield some very interesting information. The study indicated
      that the public is quite well-informed about paedophilia; its recurrence rates,
      practices and in particular the influence of the media. Furthermore, the study
      indicated quite significant differences between the cities of Belfast and
      Leicester. In conclusion, the results indicated that a moral panic connected to
      paedophilia is very present in our contemporary society.

PMID- 15573973
TI  - Criminalizing suicide attempts: can it be a deterrent?
AB  - Suicidal behaviour constitutes a serious public as well as mental health problem
      all over the world. Many developed countries have done away with the legal
      provision of punishing attempted suicides. However, in India this continues to be
      a punishable offence under the Indian Penal Code (1833). This review discusses
      the various issues related to criminalizing suicide and their implications.

PMID- 15573974
TI  - What is the significance of haemosiderin in the lungs of deceased infants?
AB  - In infants, pulmonary haemosiderin has been put forward as a marker of previous
      asphyxic abuse and possible grounds for suspicion of homicide. Review of the
      available literature does not provide a strong enough evidence base to support
      this claim. Further research is needed before instigation of criminal proceedings
      can be justified on this pathological finding.

PMID- 15573975
TI  - Case reports. 1. An autopsy case of fatal arrhythmia induced by injuries of the
      atrioventricular conduction system: a case report.
AB  - A 65-year-old woman died three days after being involved in a traffic accident,
      following an episode of ventricular fibrillation. She was diagnosed as having
      suffered cardiac contusion, liver contusion, mediastinal hematoma and rib
      fracture on admission. Her electrocardiogram showed complete right bundle branch
      block, complete atrioventricular block, and right axis deviation. Aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase and creatine
      kinase-MB were found to be elevated on biochemical blood analysis. These findings
      recovered and her condition appeared to improve daily. At autopsy, epicardial and
      intramyocardial haemorrhage were macroscopically seen in the posterior wall of
      the bilateral ventricles. On microscopic examination, there was evidence of fresh
      haemorrhage and coagulative necrosis with inflammatory reaction in the ordinary
      myocardium and adipose tissue around the atrioventricular node, which had spread
      to the proximal portion of the His' bundle. It is considered that these findings
      caused ventricular fibrillation to occur, and that the cause of death in this
      case was myocardial contusion due to blunt thoracic injury. This case would
      indicate that myocardium nearby atrioventricular junction is vulnerable to
      external force. Moreover, it would seem that fatal arrhythmia occasionally occurs
      during the follow-up stage, despite the lack of any significant clinical
      findings.

PMID- 15573976
TI  - Case reports. 2. Accidental strangulation: a case report.
AB  - Accidental strangulation, though reported, is uncommon. We report a case of an
      unusual accidental strangulation in which the floating end of the 'saree' of the
      pillion rider of a two-wheeler motorcycle got entangled in the moving rear wheel
      and constricted her neck. To our knowledge this is the first case of its type
      involving a two-wheeler motorcycle. Comments are also given on traditional Indian
      wear and safety measures required in two-wheelers to prevent such incidents.

PMID- 15573977
TI  - [Dynamics of species diversity in artificial restoration process of subalpine
      coniferous forest].
AB  - Through plot investigation and by adopting the concept of space as a substitute
      for time, the developments of species diversity of trees, shrubs and herbaceous
      plants in subalpine coniferous plantations at different restoration stages were
      studied, and the correlation coefficients of species in each layer were
      discussed. The results indicated that in the restoration process, the species
      richness, diversity and evenness in subalpine coniferous plantations were
      gradually increased in a fluctuating way. The restoration process of Picea
      asperata plantations showed a tendency of development that in favor of resuming
      species diversity. The indices of species richness (species number and Margalef
      index) and species diversity (Shannon-Wiener index and Simpson index) of trees
      increased rapidly from the early stages of plantation establishment to the stage
      of canopy closing (about 30 yr of stand age) and then presented a tendency of
      decrease with some slight fluctuations, while the index of species evenness
      showed a periodical rising trend. For the shrub layer, the indices of species
      richness (Simpson index and Macintosh index) gradually increased with increasing
      restoration years, whereas the indices of species diversity (Shannon-Wiener
      index) decreased in the early stages, sharply increased during the stages of
      canopy closing, and then slowly decreased, which exhibited a tendency of high-
      >low-->high. In the layer of herbaceous plants, the indices of species richness
      (Margalef index and number of species) and species diversity (Simpson index,
      Macintosh index and Shannon-Wiener index) presented a trend of decrease in the
      early stages of plantations establishment to canopy closing and increased later
      on. During this process, herbaceous species and their life forms changed greatly,
      with shade tolerant species gradually substituting the intolerant species. Among
      the plantations of different stand ages, the average correlation coefficients of
      trees, shrubs and herbaceous species were 41.88%, 50.61% and 37.22%,
      respectively, indicating that in the 70 years of artificial forest restoration,
      the continuity and stability of shrub species were the highest, those of
      herbaceous species showed greatest fluctuation because of the disappearance and
      regeneration occurred with the alteration of the environmental conditions of
      plantations, and those of the trees were intermediary.

PMID- 15573978
TI  - [Conservation priorities for plant species of forest-meadow ecotone in
      Sanjiangyuan Nature Reserve].
AB  - Based on field survey, information collection and experts consultation, the
      quantitative grading index system and assessment standards for preference
      conservation of rare and endangered plant species of forest-meadow ecotone in
      Sanjiangyuan Nature Reserve were established by using the methods and principles
      of systematical analysis. The quantitative grading index system included
      endangered coefficient, genetic coefficient, and useful value coefficient. In
      addition, 10 indicators used to evaluate endangered grading and conservation
      priorities sequenc, were also included in 3 subsystems respectively. Furthermore,
      the weights of 3 subsystem and 10 indicators were given through experts
      consultation and analytic hierarchy process. Endangered coefficient and
      conservation priorities coefficient, which respectively described the endangered
      grading, and preferential conservation of plant species were calculated by
      mathematic models and computer program. Contrasting to the standards of
      endangered grading and conservation priorities for plant species, we
      quantitatively evaluated the status of endangered and conservation priorities of
      plant species. The results showed that the number of endangered species was 4,
      vulnerable species 68, lower risk species 179, safety species 695; the number of
      the first class species was 8, the second class species 78, the third class
      species 164, and the delayed conservation species 696. Finally, we discussed the
      problems of indicator system and its weight, the relationship between endangered
      grading and conservation priorities sequence, and the spatial scale problem of
      plant species assessment.

PMID- 15573979
TI  - [Climatic productivity of plantations in western Liaoning area].
AB  - Calculations by six models of climatic productivity showed that the average
      climatic productivity of plantations in western Liaoning area was 8.8 t x hm(-2)
      x yr(-1), and had a decreasing trend from southeast to northwest, which was
      coincided with the distribution of rainfall. Three models were suitable to be
      used to calculate the climatic productivity of plantations in the area. The
      present plantation productivity was really lower than the potential climatic
      productivity, and the great potential was available in improving plantation
      productivity through the improvement of forest quality.

PMID- 15573980
TI  - [A comparative study on Amomum villosum cultivation under tropical wet seasonal
      rainforest and secondary forest at Xishuangbanna].
AB  - In order to protect rainforests, change the present Amomum villosum cultivation
      model, and explore the possibility of cultivating A. villosum under secondary
      forest, a comparative study was made on the growth and fruit yield of A. villosum
      cultivated under tropical wet seasonal rainforest and secondary forest at
      Xishuangbanna. The results showed that A. villosum cultivation had a significant
      effect on rainforest biomass and net productivity, but no effect on secondary
      forest. Under both rainforest and secondary forest, the order of plant density
      and biomass, from big to small, was vigorous plant, senescent plant, seedling,
      and shoot. The sum of shoot and seedlings was 3.95 and 1.66 times of senescent
      plant under rainforest and secondary forest, respectively, which meant that A.
      villosum could maintain population stability. Under rainforest, many of A.
      villosum seedlings were poorly growing old ones, and most of them could not grow
      and develop normally. The density and biomass of vigorous plant were not
      significantly different under rainforest and secondary forest, but those of
      shoot, seedling and senescent plant were significantly higher under secondary
      forest than under rainforest, suggesting that A. villosum rejuvenescence was
      faster under secondary forest. A. villosum fruit yield was 78.068 kg x hm(-2) in
      secondary forest, slightly higher than that in rainforest. It was worthwhile to
      notice that A. villosum yield was very low, its stem biomass ratio was very high
      (above 0.6), and the fruit biomass ratio was extremely low (about 0.01), which
      showed that the yield-increasing potency of A. villosum was great through
      improving biomass partition between fruit and stem. The biomass and canopy
      coverage of secondary forest was lower than those of rainforest, but the soil
      water content of secondary forest was similar to that of rainforest, which was
      favorable to the growth and development of A. villosum. The results presented
      above indicated that A. villosum could be cultivated in secondary forest.

PMID- 15573981
TI  - [Linear consociation equation set model of forest ecological benefits].
AB  - Based on the similar irrelative model of forest ecological benefits, the study
      analyzed the subordinate relations of numerous ecological benefits, and
      introduced end genetic variables Y1 and Y2 as the independent variables of
      another ecological equation to construct consociation equation set model. Leading
      from the forest's water absorption benefits, it deeply depicted the dependent and
      subordinate relations between the forest ecological benefits dependent variable
      set. Starting from the basic rule of forest ecological benefits, constructed the
      consociation equation set structure parameters matrix B and gamma restricted by
      parameter to get linear limit equation HA = L, which is the key to the forest
      ecological benefits consociation equation set. Especially, the study on the non
      linear relation of forest ecological benefits dependent and independent variable
      was the foundation of forest ecological benefits consociation equation set. The
      model was excessiveness identified and error structure matrix, not cross matrix.
      The forest absorbing water and stabling soil and keeping fertilizer and defending
      sand benefits estimate equations were gotten through the three steps least square
      estimation method with Matlab program, and the average precision was more than
      80%. From this method, the whole country forest absorbing water benefit was
      estimated as 4.7 x 10(8) t, forest fixing soil benefits was 39 x 10(8) t, forest
      keeping fertilizer benefit was 4.7 x 10(8) t and defending sand benefits was 22.8
      x 10(8) t.

PMID- 15573982
TI  - [Biomass and yield of Betula platyphylla population in Mila Mount of Tibet].
AB  - Mila Mount in Southeast Tibet is the west boundary of the horizontal distribution
      of Betula platyphylla. It is also the highest altitude area in China and the
      world, where Betula platyphylla is distributed. Based on the investigation of
      regional sample plots and the analysis of analytic trees, this paper compared the
      biomass and yield of Betula platyphylla population at different slope orientation
      and different altitude. The results showed that the growth of Betula platyphylla
      was greatly interfered by human activities. The yearly productivity of Betula
      platyphylla grown in Mila Mount was 363.1-2,072.94 kg x hm(-2), and the biomass
      was 7,625.00-33,167.00 kg x hm(-2), indicating that the biomass of Betula
      platyphylla was quite different for different population. The productivity and
      biomass of Betula platyphylla coppice after cutting were lower than those of
      seedling forest, and there existed youth broken-down in the coppice. The zonal
      changes of water resources had no significant effect on the water allocation and
      the biomass of Betula platyphylla.

PMID- 15573983
TI  - [Dynamics of microbial biomass C in a black soil under long-term fertilization
      and related affecting factors].
AB  - The effect of long-term fertilization on the dynamics of microbial biomass C in a
      typical black soil of Northeastern China was studied in a field trail treated by
      different fertilizations. The results showed that the amount of soil microbial
      biomass C under different fertilizations varied significantly with growth stages.
      It was the highest in farmyard manure (M2 and M4) treatments, with a less
      seasonal fluctuation, second in NPK treatment, the peak at sowing period, and the
      lowest in CK, the peak at wax maturity stage. No significant correlation was
      found between the dynamic changes of soil microbial biomass C and soil
      biological, physical and chemical properties in all treatments, but the
      correlation of soil microbial biomass C with the contents of N, P and K in plants
      and that of crude protein in grain was significantly positive.

PMID- 15573984
TI  - [Influence of water deficit and supplemental irrigation on nitrogen uptake by
      winter wheat and nitrogen residual in soil].
AB  - Pot experiment in greenhouse showed that water deficit at all growth stages and
      supplemental irrigation at tillering stage significantly decreased the nitrogen
      uptake by winter wheat and increased the mineral N residual (79.8-113.7 mg x kg(
      1)) in soil. Supplemental irrigation at over-wintering, jointing or filling stage
      significantly increased the nitrogen uptake by plant and decreased the nitrogen
      residual (47.2-60.3 mg x kg(-1)) in soil. But, the increase of nitrogen uptake
      caused by supplemental irrigation did not always mean a high magnitude of
      efficient use of nitrogen by plants. Supplemental irrigation at over-wintering
      stage didn't induce any significant change in nitrogen content of grain,
      irrigation at filling stage increased the nitrogen content by 20.9%, and doing
      this at jointing stage decreased the nitrogen content by 19.6%, as compared to
      the control.

PMID- 15573985
TI  - [Population of entophytic bacteria in maize roots and its dynamic analysis].
AB  - In 2001-2002, 14 maize cultivars in Liaoning Province were used for the analysis
      of their entophytic bacteria population. The entophytic bacteria strains with a
      higher frequency in maize roots were Bacillus spp., Enterobacter spp., Serratia
      spp., Pseudomonas spp., Xanthomonas spp., Clavibacter spp., Bacillus spp.,
      Enterobacter spp. and Serratia spp. Comparatively, Bacillus spp. was the most
      prevalent entophytic bacterium, including 8 species, B. subtilis, B. megaterium,
      B. cereus, B. licheniformis, B. anthracis, B. mycoides, B. pumilus and B.
      circulans, and with an average isolation frequency of 75.5% at seedling stage and
      77.6% at adult stage. There existed significant differences in the population and
      dynamics of endophytic bacteria among maize cultivars and growth periods, and a
      significant correlation was found between maize genetic background and entophytic
      bacteria population.

PMID- 15573986
TI  - [Effect of potassium application stage on photosynthetic characteristics of
      winter wheat flag leaves and on starch accumulation in wheat grains].
AB  - In this study, the same amount of potassium was applied as basal dressing
      (treatment 1) and as basal dressing and top-dressing at jointing stage (treatment
      2). The results showed that treatment 2 improved the photosynthetic rate and
      sucrose-phosphate synthase (SPS) activity of winter wheat flag leaves and the
      adenosine diphosphate glucose pyrophosphortlase (ADPGPPase) activity in wheat
      grains. It increased the supplying strength of sucrose and the accumulation rate
      of starch in the grain, and also, the grain yield. Both of the treatments
      improved the synthesis capacity of sucrose in wheat flag leaf and the
      transformation capacity from sucrose to starch in wheat grain, die to the
      coordinative relationship between source and sink of starch synthesis, including
      the synthesis, transport and transformation of photosynthate.

PMID- 15573987
TI  - [Effect of heat hardening on allocation of excitation energy in Brassica oleracea
      seedling leaves].
AB  - In this paper, Brassica oleracea was used to investigate the effect of heat
      hardening (HH) on its photosynthetic characteristics and chlorophyll fluorescence
      parameters. No distinct changes were observed in the variable fluorescence (Fv),
      photochemical quenching coefficient (qP), non-photochemical quenching coefficient
      (qN), and quantum yield of PS II electron transport (phiPS II) between HH
      treatment and control when the leaf temperature was 25-35 degrees C. When the
      leaf temperature was higher than 35 degrees C, there were obvious differences in
      the levels of Fv, qP, phiPS II and qN between HH treatment and control. For
      example, at 37 degrees C, the Fv, qP and phiPS II in HH treatment were 53%, 24%,
      and 86% higher than those in control, respectively, but the qN was 22% lower. The
      photoinhibitory quenching (qNs) in HH treatment was significantly decreased. The
      results showed that 'high energy' quenching (qNf) was an important
      photoprotection mechanism that effectively dissipated the excess excitation
      energy, protected the PS II reaction center complexes from photodamage, and
      increased the ability of resisting photoinhibition, which were consistent with
      high photosynthesis rates.

PMID- 15573988
TI  - [Earthworm feces-induced systemic resistance of cucumber against anthracnose].
AB  - Pot experiment showed that mixing earthworm feces into soil induced a
      significantly lower (P < 0.05) cucumber anthracnose than mixing peat, but had no
      significant difference (P > 0.05) with the treatment of system acquired
      resistance. The activities of polyphenol oxidase, peroxidase and phenylalanine
      ammonia-lyase in cucumber leaves treated with and without pathogen were increased
      in different degrees by mixing earthworm feces, compared with by mixing peat. All
      these suggested that mixing with earthworm feces could induce the system
      resistance of cucumber and suppress the plant disease via starting up the
      recovery enzyme system in plant.

PMID- 15573989
TI  - [Correlation analysis of simulated MODIS vegetation indices and rice leaf area
      index and leaf chlorophyll content].
AB  - This paper studied the correlations between rice leaf area index (LAI), leaf
      chlorophyll content (CHL. C), hyperspectral data, normalized difference
      vegetation index (NDVI), enhanced vegetation index (EVI), and red-edge position
      (REP). The results showed that LAI had a close correlation with visible and NIR
      bands, and CHL. C had the highest correlation with red band. A strong non-linear
      correlation was found between the LAI and REP of two rice varieties. For common
      rice, REP, EVI and NDVI were well related with LAI, but for hybrid rice, REP and
      EVI were more sensitive than NDVI to LAI. In 2003, REP, EVI and NDVI were well
      related with CHL. C.

PMID- 15573990
TI  - [Landform-based pedodiversity of some soil chemical properties in Hainan Island,
      China].
AB  - Diversity indices and abundance distribution models are the statistical tools
      having been applied by ecologists for decades to analyze the intrinsic
      regularities of various ecological entities. In this work, similar techniques
      were used to analyze the pedodiversity of some soil chemical properties in Hainan
      Island, China, and discussions were conducted on the basis of related SOTER
      digital databases. Through the calculation of the richness (S), diversity (H')
      and evenness (E) of pH value, CEC and organic matter content in surface soil of
      different landforms and the establishment and application of the multi
      distribution models of these soil chemical properties, the pedodiversity of some
      soil chemical properties of different landforms in Hainan Island in the GIS
      environment could be expressed digitally.

PMID- 15573991
TI  - [Adaptation of Eupatorium adenophorum photosynthetic characteristics to light
      intensity].
AB  - As an invasive species, Eupatorium adenophorum threatens the biodiversity
      security in Southwest China. To explore its light adaptation characteristics and
      related eco-physiological mechanism, this paper studied the physiological and
      morphological properties, e. g., gas exchange, fluorescence kinetics, chlorophyll
      content and specific leaf weight (SLW), of E. adenophorum grown in Xishuangbanna,
      China, during the dry season under four light regimes (100%, 36%, 12.5% and 4.5%
      full sunshine). Under full sunshine, the Fv/Fm and phiPS II decreased with
      increasing diurnal light intensity, but quickly re-increased when light intensity
      decreased, indicating that photoinhibition was occurred but not serious. E.
      adenophorum under full sunshine could increase excessive light energy dissipation
      through the enhancement of diurnal thermal dissipation and anti-oxidation and the
      reversible inactivation of PS II reaction center, increase light energy
      utilization, and decrease light absorption by increasing SLW and decreasing
      chlorophyll concentration. All these processes enabled E. adenophorum to avoid
      the photodamage of photosynthetic apparatus. Under low light intensities (36%,
      12.5% and 4.5% of full sunshine), E. adenophorum had a higher light absorption
      and utilization efficiency through decreasing SLW and diurnal thermal
      dissipation, increasing chlorophyll concentration, and keeping high
      photosynthetic capacity. The effective dissipation of excessive light energy
      under high light and the sufficient absorption of light energy under low light
      allowed E. adenophorum to utilize light energy effectively and grow healthily in
      a wide range of light intensity, which might be one of the reasons that made E.
      adenophorum a vigorous invader.

PMID- 15573992
TI  - [Biomass structure and production pattern of Hordeum brevisubulatum clonal
      modules under cultivated condition in the Songnen Plains].
AB  - Hordeum brevisubulatum is a typical clonal plant of grass family with short
      rhizome. In the Songnen Plains of China, the ramets of the clones were made up of
      stemming tillers and rosette seedlings by the end of the growing season.
      According to age class of the vegetative generations of tiller node, the tillers
      of the clones were divided into three age classes, and the seedlings were divided
      into four age classes. The age structures of their biomass under cultivated
      condition for two years were all of expanding types. The productivities of the
      ramets, both of the tillers and of the seedlings in the 1st age class of the
      clones, were the highest, and decreased with the increasing age class by the end
      of the growing season. The diameter of the tufts was the important quantitative
      index to measure the special size of the clones, and the number of the ramets
      could be useful to measure the growth of the clones. Statistical results showed
      that the total biomass and the biomass of the tillers, seedlings and rhizomes
      were all increased by power function with the size of tuft diameters and the
      number of total ramets, and the correlations were all significant.

PMID- 15573993
TI  - [Clonal architecture and ramet population characteristics of Lysimachia
      congestiflora growing under different light conditions].
AB  - The response of clonal architecture and ramet population characteristics to
      resource heterogeneity is of great ecological significance. This paper studied
      the variations of clonal architecture and ramet population characteristics of
      stoloniferous herb Lysimachia congestiflora growing at the open land of forest
      edge, forest edge, and forest understory of evergreen broad-leaved forest in Mt.
      Lingyan of Dujiangyan, Sichuan Province, and compared the stolon internode
      length, frequency distribution of stolon internode length, braching intensity,
      branching angle, frequency distribution of branching angle, ramet population
      density, ramet population height, ramet population biomass, and root/shoot of
      ramet population among the three habitats. The results showed that the stolon
      internode length, branching intensity, ramet population density and ramet
      population biomass were different among three habitats. Kruskal Wallis test
      indicated that the distributions of stolon internode length and branching angle
      were significantly different among three habitats. The skewness in distribution
      of stolon internode length was in the order of open land of forest edge>forest
      edge>forest understory; and the branching angle, ramet population height, and
      root/shoot of ramet population were significant greater in open land of forest
      edge than in forest edge and forest understory. The skewness in distribution of
      branching angle in open land of forest edge was smaller than that in forest edge
      and forest understory. The branching angle, ramet population height, and
      root/shoot of ramet population were not significantly different between forest
      edge and forest understory. These results were discussed in the context of
      resource acquisition strategy by clonal plants.

PMID- 15573994
TI  - [Ecological characteristics of phytoplankton in coastal area of Pearl River
      estuary].
AB  - Five cruises of phytoplankton survey were made in costal area of Pearl River
      estuary in 1998-1999. The results showed that 239 species were identified, 72.4%
      of which belonging to Bacillariophyta, 23.8% to Pyrrophyta, and 3.8% to others.
      The dominant species were warm and eurythermic species Thalassiothrix
      frauenfeldii, Nitzschia delicatissima, Thalassiothrix frauenfeldii and
      Thalassiosira subtilis, and changed with an obvious seasonal succession. The cell
      density ranged from 0.2 x 10(4) to 2,767.1 x 10(4) cell x m(-3), with an average
      of 98.7 x 10(4) cell x m(-3), and the mean cell density was obviously higher in
      summer and winter than in spring and autumn. The regional variation revealed that
      the cell density in shore area was visibly higher than that in offshore area, and
      the largest density area was at the southeast of Shangchuan Island all the year
      around. The range of mean Shannon-Wiener index, Pielou evenness index and
      biodiversity threshold was 2.63-3.17, 0.53-0.71 and 1.74-2.23, respectively.
      According to the diversity index, it was concluded that the diversity level of
      phytoplankton community in coastal area of Pearl River estuary was relatively
      high and stable.

PMID- 15573995
TI  - [Ecological regulation services of Hainan Island ecosystem and their valuation].
AB  - Ecosystem services imply the natural environmental conditions on which human life
      relies for existence, and their effectiveness formed and sustained by ecosystem
      and its ecological processes. In newly research reports, they were divided into
      four groups, i. e., provisioning services, regulation services, cultural
      services, and supporting services. To assess and valuate ecosystem services is
      the foundation of regional environmental reserve and development. Taking Hainan
      Island as an example and based on the structure and processes of natural
      ecosystem, this paper discussed the proper methods for regulation services
      assessment. The ecosystems were classified into 13 types including valley rain
      forest, mountainous rain forest, tropical monsoon forest, mountainous coppice
      forest, mountainous evergreen forest, tropical coniferous forest, shrubs,
      plantation, timber forest, windbreak forest, mangrove, savanna, and cropland, and
      then, the regulation services and their economic values of Hainan Island
      ecosystem were assessed and evaluated by terms of water-holding, soil
      conservancy, nutrient cycle, C fixation, and windbreak function. The economic
      value of the regulation services of Hainan Island ecosystem was estimated as
      2035.88 x 10(8)-2153.39 x 10(8) RMB yuan, 8 times higher to its provisioning
      services (wood and agricultural products) which were estimated as only 254.06 x
      10(8) RMB yuan. The result implied that ecosystem regulation services played an
      even more important role in the sustainable development of society and economy in
      Hainan Island.

PMID- 15573996
TI  - [Landscape spatial changes in Shenzhen and their driving factors].
AB  - Based on GIS technology, the MSS image in 1978 and the TM images in 1986, 1990,
      1995 and 1999 were used to study the landscape spatial changes in Shenzhen during
      the past two decades. The results showed that the regional landscape in Shenzhen
      changed dramatically, from a typical agricultural landscape to a rapidly
      urbanizing landscape. The percentage of cultivated land decreased from 31.06% to
      2.67%, while that of built-up area increased from 0.33% to 22.52%. The landscape
      diversity index showed a tendency of increase in 1978-1995, followed by a
      decrease in 1999. The index of landscape contagion decreased firstly and then
      increased, and the landscape fragmentation index increased from 0.0042 to 0.0073.
      Modified fractal dimension index showed the same tendency as landscape contagion
      index. Human activity was the main driving factor for landscape change. The
      change of geometry shape of landscape patches was driven by the economic
      interests of individual economic cells, and that of spatial configuration of
      landscape components was associated with the allocation of industries. The
      diversity of the whole landscape was mainly associated with the natural and
      ecological conditions such as topography and landform, while its change was
      strongly affected by the whole level of social and economic development.

PMID- 15573997
TI  - [Adaptability of abnormal tadpole (Rana chensinensis) to water pH, salinity and
      alkalinity in Changbai Mountain of China].
AB  - Under field condition with 16-18 degree C water temperature, single-factor acute
      toxicity test was used to study the toxicity effects of water pH, salinity and
      carbonate-alkalinity on abnormal tadpole (R. chensinensis). The results showed
      that when the water salinity was 0.18 g x L(-1), carbonate-alkalinity was 1.41
      mmol x L(-1), and water pH was 4.3-9.7, the survival rate of abnormal tadpole
      within 96 hours was not affected. The upper limit of LC50 for the pH within 24,
      48, 72 and 96 hours was 10.33, 10.18, 10.08 and 10.02, and the prescribed minimum
      was 3.92, 4.07, 4.11 and 4.16, respectively. The upper limit of LC0 was 9.95,
      9.80, 9.70 and 9.70, and the prescribed minimum was 4.23, 4.45, 4.30 and 4.30,
      and that of LC100 was 10.70, 10.55, 10.45 and 10.33, and the prescribed minimum
      was 3.55, 3.70, 3.92 and 4.03, respectively. The survival rate of abnormal
      tadpole within 96 hours was not affected in the water salinity between 2.0-3.0 g
      x L(-1). When water pH was 7.0-8.5 and carbonate-alkalinity was 1.41 mmol x L(
      1), the LC50 of the salinity within 24, 48, 72 and 96 hours was 8.21, 7.25, 5.17
      and 3.70 g x L(-1), the LC0 was 7.14, 6.00, 2.67 and 2.20 g x L(-1), and the
      LC100 was 9.98, 9.00, 7.67 and 5.20 g x L(-1), respectively, while the SC was
      1.70 g x L(-1). Under the same water pH and when the water salinity was 0.18 g x
      L(-1), the LC50 of carbonate-alkalinity within 24, 48, 72 and 96 hours was 14.36,
      11.83, 10.35, and 7.68 mmol x L(-1), the LC0 was 8.76, 8.51, 4.65 and 3.88 mmol x
      L(-1), and the LC100 was 19.96, 15.14, 16.05 and 11.48 mmol x L(-1),
      respectively, while the SC was 1.70 mmol x L(-1). The survival rate of abnormal
      tadpole (R. chensinensis) was decreased with increasing water pH, salinity and
      carbonate-alkalinity. The optimum water salinity and carbonate-alkalinity to the
      survival and the growth of abnormal tadpole (R. chensinensis) were below 2.0 g x
      L(-1) and 3.0 mmol x L(-1), respectively, and water pH was between 6.0 and 9.0.

PMID- 15573998
TI  - [Niches of dominant grub populations in different athletic areas of golf course].
AB  - The study on the temporal niche, spatial niche and spatial distribution of
      dominant grub populations in different athletic areas of golf courses in
      subtropics showed that except the lower temporal niche breadths of individual
      grubs in greens III and IV, the dominant grub populations in 4 areas of fairways
      and greens all had a >0.9 temporal niche breadth. The temporal niche breadth of 4
      grub species in fairway highland and greens I and II was the highest, and that in
      rough highland and green IV was the lowest. For the grub species except
      Holotrichi-avata, the one-sided low vertical spatial niche breadth was 0.2-0.7.
      The temporal niche overlap in fairways and greens of 4 grub species was above
      0.8, and the spatial niche overlap of great majority grub species was about 0.1
      0.6. The spatial niche overlap between Anomala corpulenta and Anomala cupripes in
      fairways was the highest (>0.8), and that between Anomala corpulenta and Anomala
      cupripes and between Holotrichi asauteri and Holotrichi-avata in greens was the
      highest (>0.8). 4 grub species in fairways and greens mainly activated in 0-5 and
      5-10 cm soil layers, a few grubs in 10-15 cm soil layer of fairway, and 4 grub
      species almost could not activate and feed in 10-15 cm soil layer of green.

PMID- 15573999
TI  - [Influence of temperature and light on the growth and development of Tenodera
      angustipennis and related preying functional responses].
AB  - Tenodera angustipennis was raised under laboratory conditions to study the
      influence of temperature and light on the growth and development of its nymphs.
      The functional responses of T. angustipennis to Plutella xylostella (L.) larvae
      and adults and to Lipaphis erysimi (Kaltenbach) were also studied. The results
      showed that temperature remarkably affected the growth and development of T.
      angustipennis, but light did not. The Holling models could well describe the
      functional responses of T. angustipennis to P. xylostella and L. erysimi.

PMID- 15574000
TI  - [Seasonal dynamics of arthropod community diversity, evenness and relative
      stability in peach orchards].
AB  - This study showed that the diversity index of total arthropod community in peach
      orchards was significantly correlated to the diversity index of both phytophages
      (r = 0.9480) and predators sub-communities (r = 0.7855), and the two sub
      communities were correlative (r = 0.6741). It was also significantly correlated
      to the evenness index of total community (r = 0.7870), but not correlated to the
      evenness index of both sub-communities. The diversity index (H') of total
      community was significantly correlated to the ratio of predators individuals (Sd)
      and phytophages individuals (Sz) (r = 0.8112) and of species (Ss) and individuals
      (Si) (r = 0.9188), but not correlated to the ratio of predators (Spl) and
      phytophages (Szl).

PMID- 15574001
TI  - [Effects of six host plants on the development and fecundity of Cicadulina
      bipunctella].
AB  - The study on the development, survivorship and fecundity of Cicadulina
      bipunctella reared on corn, wheat, sorghum, rice, millet, barley and Leptochloa
      panacea showed that the insect could develop and reproduce on all test host
      plants except for Leptochloa panacea. The development duration of C. bipunctella
      at its immature stages reared on sorghum was the shortest (24.1 d), then on corn
      (24.2 d), and the longest on wheat (25.5 d). The survival rate (40.8%), longevity
      (12.2 d) and oviposition per female (12.3 eggs) of female adults reared on rice
      were lower than those reared on the other five host plants. Based on the life
      table parameters, the most suitable host plants for the development and
      reproduction of C. bipunctella were millet and corn, followed by sorghum, barley,
      wheat and rice.

PMID- 15574002
TI  - [Clustering analysis and optimal cut-apart of arthropod community in megranate
      orchard].
AB  - Based on the principles of community ecology and by the method of fuzzy
      clustering, this paper studied the temporal and quantitative dynamics of the
      arthropod community and sub-community in megranate orchard, aimed to utilize
      natural enemy resources for pests control. The results showed that both of total
      community and natural enemy sub-community could be grouped into 4 clusters, and
      non-natural enemy sub-community could be grouped into 3 clusters. This clustering
      reflected the complexity of the community structure. The optimal cut-apart could
      divide the total community and sub-community into 3 stages, i. e., April-August,
      September-October, and November.

PMID- 15574003
TI  - [Effect of nitrogen fertilization and square loss on cotton aphid population,
      cotton leafhopper population and cotton yield].
AB  - The study on the effects of nitrogen fertilization (0-450 kg x hm(-2)) and square
      loss (0-12 x plant(-1)) on cotton aphid population, cotton leafhopper population
      and cotton yield showed that there were no significant differences in cotton
      aphid population, cotton leafhopper population, and numbers of effective bolls
      between transgenic Bt cotton and non-transgenic cotton. Cotton aphid populations
      on the two cottons were significantly influenced by nitrogen fertilization and by
      the interaction of nitrogen fertilization and square loss, while leafhopper
      populations were not significantly influenced by them. Nitrogen fertilization at
      squaring and flowering stage was one of important factors affecting cotton yield.
      There was a positive correlation between the application rate of nitrogen
      fertilizer and cotton yield, but a negative correlation between the number of
      lost square per plant and the yield of the two cottons.

PMID- 15574004
TI  - [Wastewater treatment efficiency of combined aluminum-starch flocculant].
AB  - This paper examined the efficiency of a combined flocculants synthesized by
      aluminum and starch (noted as CAS) in treating kaolin suspension, domestic
      wastewater, municipal effluent and pulp-making wastewater. Jar test results
      showed that the flocculent performance of CAS was prior to polyaluminum-chloride
      (PAC) in treating different concentration kaolin suspension samples (100, 400 and
      2000 mg x L(-1)). The optimal dose of CAS to each sample was 3.0, 2.0 and 2.0 mg
      x L(-1), being 60%, 50% and 50% of PAC, respectively. CAS also showed a priority
      to PAC in removing the COD and turbidity of domestic and municipal effluents.
      When treating pulp-making wastewater, the optimal dose of CAS was 70% of PAC. The
      removal rate of COD was enhanced 10%, the sludge was reduced 40%, and the
      sediment time was greatly shortened. It was also identified that the optimal
      concentration required to affect flocculation depended on the concentration and
      the character of the wastewater within the range examined. CAS was more effective
      in treating high turbidity wastewater.

PMID- 15574005
TI  - [Purification of eutrophicated water by aquatic plant].
AB  - In this study, aquatic plants were used to control the pollution of eutrophicated
      water. The results showed that aquatic plants had a higher ability to remove
      total nitrogen (TN), total phosphorus (TP) and nitrate nitrogen. Among them,
      foxtail alga (Myriophyllum verticillatum) and grain leaf pondweed (Potamogeton
      maackianus) could effectively remove TN (83.84% and 77.54%), TP (91.3%) and
      nitrate nitrogen (95.85% and 90.65%), but had no significant effect on removing
      ammonia nitrogen (only 14% to 70%). Sediment shielded by plastic could prolong
      the release of the nutrients from it for 15 to 20 days, and show the compensation
      effect later. The results also showed that aquatic plants could greatly improve
      the transparency of water, but could not improve the COD and DO of water
      effectively.

PMID- 15574006
TI  - [Lead absorption by weeds from lead-polluted soil].
AB  - A pot experiment with red soil was installed in 2002 and 2003 to study the impact
      of lead pollution on weed growth, its lead and nutrients uptake, and AMF
      colonization. The results showed that lead pollution had no significant influence
      on weed growth, and the absorbed lead was mainly accumulated in root system. The
      impact of lead pollution on nutrients uptake by weeds was depended on weed
      species, their growth stages, and kinds of nutrients. No significant difference
      was found between lead treatment and control in nutrient contents except
      potassium in Digitaria adscendens at its early growth stages, and lead had little
      influence on the absorption of nutrients by Kummerowia striata, Ixeris chinensis,
      Digitaria adscendens and Echinochloa crusgalli var. mitis. The phosphorus content
      in Ixeris chinensis and Digitaria adscendens at their ripen stage sampled from
      lead-polluted soil was significantly higher than that from control, while the
      nitrogen content in matured Echinochloa crusgalli var. mitis sampled from
      polluted soil was significantly lower than that from the control. There existed
      great difference of mycorrhizal colonization among various weed species. The
      infection rate of Kummerowia striata and Digitaria adscendens showed a slight
      difference between lead treatment and control both at vegetative and ripen stage.
      Lead pollution hindered the colonization of Ixeris chinensis. In lead-polluted
      soil, the AMF infection rate of Ixeris chinensis was 45.52% at vegetative stage
      and 74.64% at ripen stage, while in the control, it was 69.44% at vegetative
      stage and 82.21% at ripen stage. Echinochloa crusgalli var. mitis, an annual
      weed, showed an opposite response of AMF colonization to lead pollution. The
      colonization rate of AMF in Echinochloa crusgalii var. mitis root was higher
      under lead pollution condition, being 82.45% at vegetative stage and 91.36% at
      ripen stage, while in the control, it was 59.19% and 78.28%, respectively.

PMID- 15574007
TI  - [Accumulation of di-(2-ethylhexyl) phthalate in various genotype Ipomoea aquatica
      paddy soil system].
AB  - Various genotypes of Ipomoea aquatica were pot-cultured on paddy soils with
      different pollution level of di-(2-ethylhexyl) phthalate (DEHP), and the
      concentrations of DEHP in plant and soil were determined by GC/MS. The results
      showed that the concentration of DEHP in plant varied directly with soil
      pollution level, and different genotypes of Ipomoea aquatica had significantly
      different concentrations of DEHP, which varied directly with leaf area. Soils
      grown with various genotypes of Ipomoea aquatica also had significantly different
      DEHP concentrations. The soil DEHP bioaccumulation factors (BCFs) of various
      Ipomoea aquatica genotypes were all under 1.0 and in inverse proportion to soil
      pollution level. The BCFs varied significantly among the genotypes of Ipomoea
      aquatica, with a relatively higher value for those genotypes with middle size
      leaves.

PMID- 15574008
TI  - [Effect of organophosphorous insecticides on Chinese chive insect pests and their
      degradation by pesticide-degrading bacterium].
AB  - 3.00 kg(a. i) x hm(-2) phoxin and 2.63 kg(a. i) x hm(-2) methyl parathion were
      respectively applied to control the Taeniothrips alliorum on Chinese chive.
      Compared to no pesticide treatment, the decline rate of the insect density was
      98.28% and 98.39% at the 3rd day after spraying pesticides, and 89.94% and 94.04%
      at the 20th day after spraying pesticides, respectively. At the 3rd day after
      spraying 15.00, 18.00 and 21.00 kg(a. i) x hm(-2) phoxin, the insect density of
      Bradysia odoriphaga decreased 80.77%, 93.10% and 96.98%, and at the 35th day
      after spraying, it decreased 92.44%, 95.05% and 96.81%, respectively. The
      application of pesticide-degrading bacterium had not any effect on controlling
      insect pests, but could markedly degrade pesticide. At the 3rd day after spraying
      45.00 L x hm(-2) pesticide-degrading bacterium to control Taeniothrips alliorum,
      the degradion rate of phoxin and methyl parathion was 99.52% and 98.83%, and at
      the 3rd after spraying 75.00 L x hm(-2) pesticide-degrading bacterium to control
      Bradysia odoriphaga, the degradation rate of three concentrations of phoxin was
      100%, 100% and 99.69%, respectively.

PMID- 15574009
TI  - [Effect of Jinggang Mountain forests on regional ecological environment].
AB  - Based on the late years' data of forest resources, climate, hydrology and
      atmosphere in Jinggang Mountain region and by the methods of canonical
      correlation analysis and multiple linear stepwise regression, this paper analyzed
      the influence of forests on the climate, water quality and atmosphere of this
      region. The results showed that forest volume had an evident effect on maximum
      daily precipitation, extreme highest air temperature and atmospheric SO2
      concentration, and on COD(cr) and ammonic nitrogen contents in river water. The
      greater the regional forest volume, the less maximum daily precipitation and the
      lower extreme highest air temperature, atmospheric SO2 concentration and water
      COD(cr) and ammonic nitrogen contents. Forest cover percentage could remarkably
      affect soil erosion modulus and atmospheric NOx concentration: the two latter
      were decreased as forest cover percentage increased. These results will provide
      theoretic foundation for the evaluation of the environmental value and ecological
      benefit of forest.

PMID- 15574010
TI  - [Forest Inventory Data (FID)-based biomass models and their prospects].
AB  - Forest Inventory Data (FID)-based biomass models are important methods in
      assessing forest biomass at landscape, regional, and national scales, and play an
      important role in studying terrestrial carbon budget and global changes. In this
      paper, Forest Inventory Data were reviewed, FID-based models were summarized, and
      shortages of FID-based models were analyzed. Based on these analyses, the future
      tasks were pointed out: 1) Comprehensive effect of forest biological factors and
      non-biological factors on forest biomass, especially on forest volume and age; 2)
      Identification of the relationships between total forest biomass and live wood
      biomass; 3) Development of remote sensing- and FID-based forest biomass models.
      These researches will provide new methods and theoretical bases for estimating
      forest biomass and carbon budget.

PMID- 15574011
TI  - [A discussion on basic content and evaluation index system of agroecosystem
      health].
AB  - Agroecosystem health is the fundament of food security and human health, and
      becoming one of the hot spots and frontier fields in agricultural ecology study
      with more and more international concerns, which can be interpreted as a
      sustainable state and a dynamic process involving good eco-environment, healthy
      agricultural organisms, rational spatial and temporal structure, clean production
      pattern, optimal biodiversity and high productivity. Agroecosystem is a kind of
      typical artificial and natural compound ecosystem. Its health is strongly
      influenced and controlled by human activities, and usually linked with agro
      products quality, food security and biological security. A series of indices
      including biological, environmental and eco-economic indicators could be
      integrated to assess the situation and level of agroecosystem health, and some
      methods including comprehensive index assessment, eco-toxicological assessment
      and ecological risk assessment could be used for the evaluation of agroecosystem
      health.

PMID- 15574012
TI  - [Effect of ecological factors on citrus fruit quality].
AB  - This paper summarized the research advance on the physiological foundation of
      citrus fruit's major quality factors such as color formation and organic acid and
      sugar accumulation, and analyzed the effects of main ecological factors such as
      temperature, sunshine, water, soil, terrain and landforms on them. The existing
      problems and the research prospects of citrus ecology were expounded, and a
      useful proposal on the quality sub-distribution of citrus in China was put
      forward.

PMID- 15574013
TI  - [Research advance in application of RAPD techniques in entomology].
AB  - This paper summarized the application of RAPD techniques in insect taxology and
      ecology, relative of species, systemic development, identification of pest,
      diagnosing for pest resistance, construction of molecular linkage map, and
      molecular assistant breeding. The problems existing in the applications of RAPD
      in entomology were indicated, and their countermeasures were given. It was
      mentioned that with the development of theories and experimental techniques,
      insect molecular biology would make new progress and conquer all those problems.

PMID- 15574014
TI  - [Research advance in polyphosphate-accumulating microorganisms in enhanced
      biological phosphorus removal process].
AB  - This paper discussed the function of enhanced biological phosphorus removal
      (EBPR) in P pollution control, P containing wastewater treatment and P resources
      recovery, and summarized the metabolic characteristics, research progress and
      methodologies of polyphosphate-accumulating organisms (PAOs). Although
      polyphosphate has been found in many organisms, only few of PAOs were isolated,
      cultured and identified. Culture medium formulation is the key to isolate PAOs
      and to study the microbial accumulation of polyphosphate, and the competition of
      glycogen-accumulating organisms (GAOs) with PAOs for carbon resources is one of
      the reasons of low EBPR efficiency. Modern scientific methods such as fluorescent
      in situ hybridization, confocal laser scanning microscope, microautoradiography,
      and in vivo NMR spectroscopy, provided powerful tools to analyze PAO species
      composition, spatial structure and functional properties under field conditions.
      The knowledge of PAO is valuable to enhance the P removal efficiency in water
      treatment plant, and to improve our understanding on P transformation and
      transferring in environment.

PMID- 15574015
TI  - Fillings needed as PCTs are handed responsibility for stopping the rot.

PMID- 15574016
TI  - On location: Shropshire and Staffordshire. Aiming high: firm foundation on mental
      health.

PMID- 15574017
TI  - Take care--they do read all about it.

PMID- 15574018
TI  - Clinical management. Where medicine meets management. Heart to heart.
AB  - The James Cook University Hospital appointed a cardiology pathways co-ordinator
      to reduce waits for those with acute coronary syndromes. The approach, in line
      with the coronary heart disease national service framework, has reduced error,
      duplication and delay.

PMID- 15574019
TI  - Management. Gently does it.
AB  - Soft intelligence is information gathered from conversations, observations and
      experiences that allow judgements to be made. Research by York University shows
      that less than one in four of those interviewed used hard data to inform their
      judgements of NHS trusts. Sources of soft information can be direct: based on
      first-hand experiences; and indirect: the accounts and views of colleagues,
      patients, public, friends, journalists.

PMID- 15574020
TI  - Finance. Heed the lessons and go up a class.

PMID- 15574021
TI  - HSJ people. Happy returns.

PMID- 15574023
TI  - Running the ethics race.

PMID- 15574024
TI  - Physiological measures in intensive care.

PMID- 15574025
TI  - Degrees of support.

PMID- 15574026
TI  - Breastfeeding in the neonatal unit: a case review.

PMID- 15574027
TI  - Oncology outreach: history in the making.

PMID- 15574028
TI  - Risk of anaphylaxis: improving care at school.

PMID- 15574029
TI  - Safeguarding children through police checks: a discussion.

PMID- 15574030
TI  - Therapeutic plasma exchange in children.

PMID- 15574031
TI  - DoH hands over responsibility for pay.

PMID- 15574032
TI  - DoH plans on hospital hygiene and MRSA are unrealistic.

PMID- 15574033
TI  - Critical care. Why it is now vital for all nurses to have skills in this area.

PMID- 15574034
TI  - Wiping out infection.

PMID- 15574035
TI  - Patients behaving badly.

PMID- 15574036
TI  - Implementing new guidelines on epilepsy management.
AB  - New guidance has been released by the National Institute for Clinical Excellence
      on the diagnosis and management of epilepsies in adults, children and young
      people. Appropriate treatment and management can result in up to 70 per cent of
      people with epilepsy living seizure free. However, there are concerns regarding
      the shortage of specialists to implement the new guidance.

PMID- 15574037
TI  - What you need to know about threadworm.

PMID- 15574038
TI  - Diazepam.

PMID- 15574039
TI  - The use of light therapy to lower agitation in people with dementia.
AB  - Agitation and sleep disturbance are problematic for people with dementia and
      their carers, and have been linked to disrupted circadian rhythms caused by a
      lack of exposure to light. Bright light therapy (BLT) offers a powerful and cost
      effective alternative to pharmacological options, and can be easily incorporated
      into care routines. This article describes practical issues faced when
      implementing light therapy in a nursing home setting, and attempts to address
      existing perceptions about its effectiveness.

PMID- 15574040
TI  - Monitoring patients on lithium in the primary care setting.

PMID- 15574041
TI  - Practical Procedures. IM injection.

PMID- 15574042
TI  - Understanding the blood group system and blood transfusions.
AB  - Having a blood transfusion carries risks for patients. To minimise these risks,
      nurses must be aware of the ABO group system, components of blood and how they
      should be stored, handled, checked and administered. They must also be aware of
      possible adverse events during or after transfusion, how to monitor patients and
      how to deal with adverse events should they occur. All staff involved at any
      stage must be trained and aware of hospital policy and all actions must be
      accurately recorded to ensure the process is as safe as possible.

PMID- 15574043
TI  - Stand up and be heard at presentations.

PMID- 15574044
TI  - Keep the ball rolling.

PMID- 15574046
TI  - Too many hands?

PMID- 15574045
TI  - The price of success.

PMID- 15574047
TI  - The value of values.

PMID- 15574048
TI  - Caring as a craft.

PMID- 15574049
TI  - A profession like no other.

PMID- 15574050
TI  - It's all in the mind.

PMID- 15574051
TI  - Blind believers.

PMID- 15574052
TI  - Concept mapping--a strategy for assessment.
AB  - Rapidly expanding knowledge has led to changing approaches to teaching, learning
      and assessing. The emphasis is on student-centred approaches that encourage
      lifelong learning skills. One such approach to learning is concept mapping. The
      case study in this article discusses the use of mapping as a successful strategy
      for assessment.

PMID- 15574053
TI  - Rectal irrigation for relief of functional bowel disorders.
AB  - This article examines the use of rectal irrigation for the symptomatic relief of
      functional bowel disorders in certain groups of patients. The authors undertook a
      study of 80 patients and conclude that it is a valuable treatment for some
      patients.

PMID- 15574054
TI  - Pathways for evidence-based continence care.
AB  - In this article the authors provide an overview of the continence care pathway
      they designed in 2001. The aim of continence care pathways is to enable nurses to
      provide evidence-based care to patients in any clinical setting.

PMID- 15574055
TI  - Evaluation of Australia's National Notifiable Disease Surveillance System.
AB  - The Australian National Notifiable Diseases Surveillance System (NNDSS) is a
      passive surveillance system that collects information on communicable diseases.
      The Australian Government manages NNDSS under the auspices of the Communicable
      Diseases Network Australia (CDNA). Data collected by each state and territory are
      collated, analysed and disseminated by the Australian Government Department of
      Health and Ageing. We report the first evaluation of NNDSS since it was
      established in 1991. Three primary stakeholder groups were surveyed: (a) CDNA
      members, (b) the National Surveillance Committee and (c) the readership of
      Communicable Diseases Intelligence, the primary means of data dissemination from
      NNDSS. The evaluation revealed that the system was acceptable, structurally
      simple, and that the data collected were actively used by stakeholders. However,
      the lack of clearly documented aims and objectives for NNDSS, inflexibility to
      changing needs, lack of timeliness and complexity in processes were seen as
      problematic. The results of this evaluation, supported by recent federal funding
      to enhance national biosecurity, will provide the framework for enhancing NNDSS
      to meet national communicable disease surveillance requirements in Australia.

PMID- 15574056
TI  - Surveillance of adverse events following immunisation: Australia 2002 to 2003.
AB  - Reports of suspected adverse events following immunisation (AEFI) are reviewed by
      the Adverse Drug Reactions Advisory Committee and collated in a central database.
      We analysed AEFI records for vaccines administered during October 2002 to
      December 2003, and assessed AEFI reporting trends for 2000 to 2003. AEFI
      reporting rates were calculated using denominator data from the Australian
      Childhood Immunisation Register and the annual national influenza vaccination
      coverage survey. A total of 1,744 AEFI records were analysed for October 2002 to
      December 2003. The majority described non-serious events; 9 per cent (n=149)
      described AEFIs defined as 'serious'. Four deaths were reported but none were
      causally related to immunisation. Dose-based AEFI reporting rates were 2.1 per
      100,000 doses of influenza vaccine for adults aged 40 years or over and 19.8 per
      100,000 doses of scheduled vaccines for children aged <7 years. The most
      frequently reported individual AEFI was injection site reaction in children after
      a fourth or fifth dose of an acellular pertussis-containing vaccine (54 and 98
      reports per 100,000 doses respectively). The most frequently suspected vaccine
      was meningococcal C conjugate vaccine (34% of reports-mostly injection site
      reactions, gastrointestinal symptoms and headaches). The average annual reporting
      rate was 7.0 per 100,000 population, the highest to date. The increase in the
      AEFI reporting rate was due to a greater number of children becoming eligible to
      receive a fourth or fifth consecutive dose of acellular pertussis vaccine and the
      introduction of the meningococcal C vaccination program in January 2003 for those
      aged 1-19 years. The low reporting rate of serious AEFIs demonstrates the high
      level of safety of vaccines in Australia.

PMID- 15574057
TI  - Annual report of the Australian National Poliovirus Reference Laboratory, 2003.
AB  - The Australian National Poliovirus Reference Laboratory was established in late
      1994, as part of Australia's commitment to the World Health Organization's (WHO)
      polio eradication program. The laboratory continues to play a pivotal role in
      maintaining Australia's polio-free status through surveillance for cases of acute
      flaccid paralysis (AFP), the main clinical presentation of poliomyelitis, and the
      testing of specimens from these cases. The annual notification rate for eligible
      cases of AFP in Australia for 2003 was 0.83 per 100,000 children less than 15
      years of age. The annual non-polio AFP rate after classification of cases by the
      polio expert committee was 0.68 per 100,000, 32 per cent below WHO's annual
      target. While no polioviruses were isolated from the specimens tested from the 27
      cases of AFP in 2003, a novel enterovirus (enterovirus 75) was isolated from one
      case and enterovirus 71 was isolated from another. During the same period 12
      polioviruses, referred from cases other than AFP, tested as Sabin-like by the WHO
      approved methods of intratypic differentiation. The importation of wild
      polioviruses from endemic Nigeria into surrounding countries of Africa during
      2003, highlights the importance of the continuation of AFP surveillance and high
      quality laboratory activities throughout the world until global eradication of
      polio is certified.

PMID- 15574058
TI  - An outbreak of meningococcal disease in a secondary school--implications for
      public health practice.
AB  - This report describes briefly the management of three cases of meningococcal
      disease which all occurred within one week at a secondary school on the Central
      Coast of New South Wales in late winter 2003. The Central Coast health area has a
      population of approximately 300,000. Between 10 and 15 cases of meningococcal
      disease are notified to the Central Coast Public Health Unit each year. The three
      cases all presented to Gosford Hospital, Cases 1 and 2, both in Year 9, on
      Thursday 14 August 2003 and Case 3 in Year 8 on Friday 15 August 2003.

PMID- 15574059
TI  - Festschrift for Professor Margaret Burgess AO.
AB  - In honour of the retirement of our director Margaret Burgess, National Centre for
      Immunisation Research and Surveillance (NCIRS) held a Festschrift on 5th to 6th
      February 2004. The themes of the event were Vaccines for the 21st Century and
      Congenital and Neonatal Infections. International guests attended the
      Festschrift, as well as over 180 colleagues and co-workers from across Australia.
      A summary of the presentations over these two fascinating days is provided
      herein.

PMID- 15574060
TI  - Creutzfeldt-Jakob disease surveillance in Australia January 1970 to December
      2003.
AB  - The Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR) was
      established by the Commonwealth Government in October 1993 in response to the
      recognition of four probable human pituitary hormone related Creutzfeldt-Jakob
      disease (CJD) deaths. An inquiry into CJD in Australia and the use of human
      pituitary hormones under the Australian Human Pituitary Hormone Program suggested
      the expansion of some activities of the Registry to include retrospective case
      ascertainment from 1 January 1970. In parallel with monitoring possible medically
      acquired (iatrogenic) cases of CJD, the ANCJDR prospectively monitors and
      investigates all suspect cases of transmissible spongiform encephalopathies
      occurring within the states and territories of Australia, including sporadic and
      familial, and the potential occurrence of variant CJD. The ANCJDR also actively
      participates in an international surveillance consortium. This brief report
      summarises methods of classification and ascertainment as well as current
      epidemiological findings and new surveillance techniques that are being adopted
      to improve case ascertainment.

PMID- 15574061
TI  - Foodborne disease investigation across Australia: annual report of the OzFoodNet
      network, 2003.
AB  - In 2003, OzFoodNet conducted enhanced surveillance of foodborne diseases across
      Australia, which covered all states and territories. During 2003, there were
      23,250 notifications of eight potentially foodborne diseases, of which 67 per
      cent and 30 per cent were due to Campylobacter and Salmonella infections
      respectively. The most common Salmonella serotype was Typhimurium, as in previous
      years. Most S. Enteritidis were acquired overseas, except for Queensland where 52
      per cent of infections were acquired locally. Locally acquired S. Enteritidis
      infections in Australia were predominantly due to phage type 26. The most common
      serotype of Shiga toxin producing E. coli was O157, although for 49 per cent of
      notified infections serotype was unknown due to the use of polymerase chain
      reaction based screening tests. There were 12 materno-foetal listeriosis
      infections in 2003, which was an increase compared to recent years. During 2003,
      there were 444 outbreaks of gastroenteritis and foodborne disease recorded.
      Ninety-nine of these were of foodborne origin affecting 1,686 persons,
      hospitalising 105 and causing six deaths. A wide range of agents and foods caused
      these outbreaks, with Salmonella Typhimurium being the most common pathogen.
      Outbreaks associated with fish and seafood dishes, poultry meat, and Asian style
      and imported foods were common. Four outbreaks with international implications
      were reported: an outbreak of Salmonella in Montevideo involving contaminated
      tahini from the Middle East and three outbreaks of norovirus infection associated
      with imported Japanese oysters. Outbreak data indicated a need to monitor food
      safety in aged care settings, restaurants and catering. Eighty-nine
      investigations into clusters of gastrointestinal illness where a source could not
      be identified were conducted, including multi-state outbreaks of salmonellosis.
      One multistate investigation of antibiotic resistant Salmonella Paratyphi b Java
      identified 18 cases who had recent exposure to tropical fish aquariums. Ninety
      seven per cent of Salmonella notifications on state and territory surveillance
      databases have complete information on serotype and phage type. In 2003,
      OzFoodNet demonstrated the benefits of national collaboration to control food
      borne disease.

PMID- 15574062
TI  - Laboratory surveillance of Shiga toxin producing Escherichia coli in South
      Australia and the Hunter Health Area, New South Wales, Australia.
AB  - To estimate the prevalence of Shiga toxin producing Escherichia coli in
      Australia, bloody stool samples from two Australian locations were screened for
      the presence of Shiga toxin genes, stx1 and stx2. Four of 126 (3.2%) and 139 of
      5,829 (2.4%) patients from the two locations had a positive polymerase chain
      reaction for Shiga toxin genes.

PMID- 15574063
TI  - Enhanced surveillance of acute hepatitis B in south-eastern Sydney.
AB  - Hepatitis B is a notifiable condition in all Australian states and territories.
      Medical practitioners and health facilities are required to report episodes of
      acute disease, while laboratories must notify on positive serological results. In
      New South Wales laboratories are required to report only the presence of
      hepatitis B surface antigen (HBsAg). Without clinical information, laboratory
      reporting of HBsAg fails to distinguish between acute infection and chronic
      carriage. Since practitioner under reporting is well recognised, surveillance
      data are likely to underestimate the true incidence of acute clinical infection.
      Two retrospective reviews of an enhanced surveillance system to improve the
      identification of acute hepatitis B in south-eastern Sydney are presented. Over a
      6-month period, the enhanced surveillance system increased the identification of
      acute cases by at least threefold. Over a 5-year period, medical practitioners or
      hospitals reported only 25 per cent of acute disease, the remainder being
      initially notified by laboratories. Approximately half of the laboratory
      notifications contained only HBsAg results. The availability of clinical notes,
      liver enzyme or IgM to core antigen results assisted the public health unit in
      the identification of possible acute disease. This system of enhanced
      surveillance has proven to be sustainable, with minimal resources required. We
      suggest that sentinel enhanced surveillance systems in a sample of New South
      Wales public health units would be an effective and efficient method to improve
      the surveillance of acute hepatitis B, and that laboratories be required to
      report IgM to core antigen, if available, when notifying a positive HBsAg result.

PMID- 15574064
TI  - Antiviral prophylaxis in the management of an influenza outbreak in an aged care
      facility.
AB  - Influenza in persons aged > or = 65 years is associated with an increased risk of
      severe complications. Residents in aged care facilities have a higher proportion
      of chronic illnesses and within closed settings there is an increased risk of
      transmission. In July 2002, a 50 bed aged care facility reported an influenza
      like illness (ILI) among residents and staff despite over 90 per cent influenza
      vaccine coverage among residents. A total of 17 of 49 residents and 9 of 43 staff
      met the case definition for ILI with onset on or after 26 June 2002. Seven people
      required hospitalisation and two died. Nasopharyngeal swabs were collected from
      symptomatic residents and staff, and influenza A was detected in six residents
      and two staff. Five unimmunised residents and 33 unimmunised staff were offered
      influenza vaccine and all residents and staff were offered oseltamivir
      prophylaxis of 75mg daily for 10 days. Subsequently, of 41 residents tested,
      seven demonstrated a fourfold or greater rise in antibody titres specific to H3N2
      yet reported no symptoms. All seven had been immunised at least eight weeks
      previously, and had taken oseltamivir prophylaxis. This outbreak was
      characterised by a high attack rate of ILI in a well-immunised community. The
      ability to access rapid diagnostic testing enabled the prompt initiation of
      antiviral prophylaxis, which may have a role in controlling influenza in this
      setting.

PMID- 15574066
TI  - Communicable diseases surveillance. Highlights for 2nd quarter, 2004.

PMID- 15574065
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, April to June 2004.
AB  - Salmonella incidence was increased during the quarter, similar to the first
      quarter of 2004. There were several outbreaks of different phage types of S.
      Typhimurium occurring in multiple Australian states. OzFoodNet held several
      discussions during the quarter to try to identify links between these increases.
      In total, Salmonella infections were responsible for 32 per cent of foodborne
      outbreaks. Large norovirus outbreaks were reported in association with food
      service industries where people had worked while ill. It is vital that people
      responsible for preparing and handling food do not work while they have symptoms
      of gastroenteritis, as the results can be devastating for food businesses.
      Imported Japanese oysters were again implicated in an outbreak of suspected viral
      illness, highlighting the need for improved control measures for these products.

PMID- 15574067
TI  - Nonlinear anisotropic diffusion filtering of three-dimensional image data from
      two-photon microscopy.
AB  - Two-photon microscopy in combination with novel fluorescent labeling techniques
      enables imaging of three-dimensional neuronal morphologies in intact brain
      tissue. In principle it is now possible to automatically reconstruct the
      dendritic branching patterns of neurons from 3-D fluorescence image stacks. In
      practice however, the signal-to-noise ratio can be low, in particular in the case
      of thin dendrites or axons imaged relatively deep in the tissue. Here we present
      a nonlinear anisotropic diffusion filter that enhances the signal-to-noise ratio
      while preserving the original dimensions of the structural elements. The key idea
      is to use structural information in the raw data-the local moments of inertia-to
      locally control the strength and direction of diffusion filtering. A cylindrical
      dendrite, for example, is effectively smoothed only parallel to its longitudinal
      axis, not perpendicular to it. This is demonstrated for artificial data as well
      as for in vivo two-photon microscopic data from pyramidal neurons of rat
      neocortex. In both cases noise is averaged out along the dendrites, leading to
      bridging of apparent gaps, while dendritic diameters are not affected. The filter
      is a valuable general tool for smoothing cellular processes and is well suited
      for preparing data for subsequent image segmentation and neuron reconstruction.

PMID- 15574068
TI  - Effects of single- vs. multiple-set resistance training on maximum strength and
      body composition in trained postmenopausal women.
AB  - The purpose of this study was to examine the effect of a single- vs. a multiple
      set resistance training protocol in well-trained early postmenopausal women.
      Subjects (N = 71) were randomly assigned to begin either with 12 weeks of the
      single-set or 12 weeks of the multiple-set protocol. After another 5 weeks of
      regenerational resistance training, the subgroup performing the single-set
      protocol during the first 12 weeks crossed over to the 12-week multiple-set
      protocol and vice versa. Neither exercise type nor exercise intensity, degree of
      fatigue, rest periods, speed of movement, training sessions per week, compliance
      and attendance, or periodization strategy differed between exercise protocols.
      Body mass, body composition, and 1 repetition maximum (1RM) values for leg press,
      bench press, rowing, and leg adduction were measured at baseline and after each
      period. Multiple-set training resulted in significant increases (3.5-5.5%) for
      all 4 strength measurements, whereas single-set training resulted in significant
      decreases (-1.1 to -2.0%). Body mass and body composition did not change during
      the study. The results show that, in pretrained subjects, multiple-set protocols
      are superior to single-set protocols in increasing maximum strength.

PMID- 15574069
TI  - Upper-body power as measured by medicine-ball throw distance and its relationship
      to class level among 10- and 11-year-old female participants in club gymnastics.
AB  - The purpose of this study was to determine whether or not a relationship existed
      between upper-body power and class level among female club gymnasts. Sixty female
      gymnasts between the ages of 10 and 11 and between class levels 5 and 8
      participated in the study. The distance of a medicine-ball throw was used to
      measure upper-body power. Three types of throws--overhead forward throw, overhead
      backward throw, and chest pass--were performed with a 6-lb rubber medicine ball.
      The mean distances of 2 trails were calculated and categorized into age group and
      class level. An analysis of variance design was used to determine the
      relationship between mean throw distances and throw type, age, and class level.
      No significant differences were found between mean throw distances and throw
      type, age, or class level. The results of this study show no relationship between
      upper-body power of female gymnasts and throw type, age, and class level.

PMID- 15574070
TI  - Effects of a knee ligament injury prevention exercise program on impact forces in
      women.
AB  - Previous research suggests high impact forces generated during landings
      contribute to noncontact anterior cruciate ligament (ACL) injuries. In women,
      neuromuscular differences appear to modify the ability to dissipate landing
      forces when compared to men. This study examined peak vertical impact forces
      (F(p)) and rate of force development (RFD) following a 9-week, low-intensity
      (simple jump-landing-jump tasks) and volume (number of foot contacts per workout)
      plyometric-based knee ligament injury prevention (KLIP) program. Female subjects
      were randomly assigned into control (n = 14) and treatment (n = 14) groups.
      Treatment subjects attended KLIP sessions twice a week for 9 weeks, and control
      subjects received no intervention. Ground reaction forces (F(p) and RFD)
      generated during a step-land protocol were assessed at study onset and
      termination. Significant reductions in F(p) (p = 0.0004) and RFD (p = 0.0205)
      were observed in the treatment group. Our results indicate that 9 weeks of KLIP
      training altered landing strategies in women to lower F(p) and RFD. These changes
      are considered conducive to a reduced risk of knee injury while landing.

PMID- 15574071
TI  - Effects of a short-term interval training program on physical fitness in
      prepubertal children.
AB  - The aim of this study was to analyze the effects of a 7-week interval-training
      program on different aspects of physical fitness in children who were 8-11 years
      old. Forty-six boys and 54 girls (9.7 +/- 0.8 years) were divided into an
      experimental group and a control group. The 2 groups performed selected tests
      from the European physical fitness test battery before and after training.
      Training consisted of 2 specific 30-minute sessions per week of short high
      intensity, intermittent-running aerobic exercises at velocities ranging from 100
      130% of maximal aerobic speed. After training, the experimental group
      demonstrated a significant improvement in the standing broad jump (9.6%, p <
      0.001, F = 12.9) and 20-meter shuttle run (5.4%, p < 0.001, F = 14.4), whereas
      for the control group, no significant changes were observed. It was concluded
      that a high-intensity, intermittent-running program improved children's aerobic
      performance and explosive strength.

PMID- 15574072
TI  - Thigh-muscles strength training, dance exercise, dynamometry, and anthropometry
      in professional ballerinas.
AB  - The purpose of the present study was to assess the effects of 12 weeks of
      quadriceps and hamstring strength training on torque levels after a dance
      exercise and on selected anthropometric parameters. The sample consisted of 22
      (ages, 25 +/- 1.3 years) full-time professional ballerinas who were randomly
      assigned into experimental (n = 12) and control (n = 10) groups. A dance routine
      designed to cause fatigue within 5 minutes, isokinetic dynamometry, and
      anthropometric assessments were conducted before and after strength training in
      both groups. Before strength training, the dance routine resulted in significant
      reductions of hamstring (p < 0.001) and quadriceps (p < 0.001) peak torques in
      both subject groups. However, after strength training, only control subjects
      demonstrated such torque decrements (p < 0.001) after the dance routine.
      Furthermore, the experimental group revealed greater knee extension (119 vs. 138
      N.m; p < 0.001) and flexion (60 vs. 69 N.m; p < 0.001) torques, smaller sum of
      skinfolds (33.6 vs. 27.8 mm; p < 0.01), more fat-free mass (37.7 vs. 39.4 kg; p <
      0.05), but unchanged body mass (p > 0.05) and thigh circumferences (p > 0.05). A
      negative relationship (p < 0.001) was found between initial strength levels and
      improvements measured at the end of the 12-week program. These results suggest
      that supplementary strength training for hamstring and quadriceps muscles is
      beneficial to professional ballerinas and their dancing; weaker individuals are
      more likely to benefit from such regimens than their stronger counterparts,
      whereas increases in thigh-muscle strength do not alter selected aesthetic
      components.

PMID- 15574073
TI  - Physiological responses to fitness activities: a comparison between land-based
      and water aerobics exercise.
AB  - This study compared the heart rate (HR) and blood lactate (BL) responses in young
      healthy women performing the same routine of aerobics exercise in 3 different
      conditions: on land, in shallow water (0.8 m), and in deep water (1.4 m). The
      average age and body mass index (BMI) of the group were 27.4 years and 22.6 kg.m(
      2), respectively. The highest HR and BL values were reached during land aerobics
      (median HR values were 138.0 and 161.5 b.min(-1), and lactate values were 3.10
      and 5.65 mmol.L(-1) at slow and at faster pace, respectively). These parameters
      were progressively reduced going from shallow water (121.5 and 154.0 b.min(-1),
      1.75 and 3.15 mmol.L(-1)) to deep water (97.5 and 113.5 b.min(-1), 1.70 and 1.75
      mmol.L(-1)). The HR measured as percentage of maximum HR varied from 48.43% to
      77.53% depending on the water depth and the pace. These data indicate that
      exercise in water significantly reduces HR and BL production compared with the
      same exercise performed on land.

PMID- 15574074
TI  - The effects of yoga training and a single bout of yoga on delayed onset muscle
      soreness in the lower extremity.
AB  - The purpose of this study was to determine the effects of yoga training and a
      single bout of yoga on the intensity of delayed onset muscle soreness (DOMS). 24
      yoga-trained (YT; n = 12) and non-yoga-trained (CON; n = 12), matched women
      volunteers were administered a DOMS-inducing bench-stepping exercise. Muscle
      soreness was assessed at baseline, 24, 48, 72, 96, and 120 hours after bench
      stepping using a Visual Analog Scale (VAS). Groups were also compared on body
      awareness (BA), flexibility using the sit-and-reach test (SR), and perceived
      exertion (RPE). Statistical significance was accepted at p </= 0.05. A 2 x 2
      mixed factorial ANOVA with repeated measures at 24 and 48 hours revealed a
      significant (p < 0.05) group main effect with VAS scores greater for CON than YT.
      Paired t-tests revealed that in YT, VAS scores were higher before yoga class than
      after yoga class at 24 hours (21.4 [+/- 6.9] mm vs. 11.1 [+/- 4.1] mm; p = 0.02).
      The SR was greater in YT than in CON (65.0 [+/- 7.9] cm vs. 33.3 [+/- 7.0] cm; p
      < 0.01); however, no differences were found between yoga and control in BA (94.0
      [+/- 4.4] units vs. 83.8 [+/- 3.7] units; p = 0.21) or in RPE at 5-minute
      intervals (2.9 [+/- 0.3], 5.3 [+/- 0.8], 5.8 [+/- 0.9], and 5.2 [+/- 0.8] vs. 2.5
      [+/- 0.3], 4.0 [+/- 0.5], 4.2 [+/- 0.3], and 4.9 [+/- 0.4]. Yoga training and a
      single bout of yoga appear to attenuate peak muscle soreness in women following a
      bout of eccentric exercise. These findings have significant implications for
      coaches, athletes, and the exercising public who may want to implement yoga
      training as a preseason regimen or supplemental activity to lessen the symptoms
      associated with muscle soreness.

PMID- 15574075
TI  - Muscular adaptations to combinations of high- and low-intensity resistance
      exercises.
AB  - Acute and long-term effects of resistance-training regimens with varied
      combinations of high- and low-intensity exercises were studied. Acute changes in
      the serum growth hormone (GH) concentration were initially measured after 3 types
      of regimens for knee extension exercise: a medium intensity (approximately 10
      repetition maximum [RM]) short interset rest period (30 s) with progressively
      decreasing load ("hypertrophy type"); 5 sets of a high-intensity (90% of 1RM) and
      low-repetition exercise ("strength type"); and a single set of low-intensity and
      high-repetition exercise added immediately after the strength-type regimen
      ("combi-type"). Postexercise increases in serum GH concentration showed a
      significant regimen dependence: hypertrophy-type > combi-type > strength-type (p
      < 0.05, n = 8). Next, the long-term effects of periodized training protocols with
      the above regimens on muscular function were investigated. Male subjects (n = 16)
      were assigned to either hypertrophy/combi (HC) or hypertrophy/ strength (HS)
      groups and performed leg press and extension exercises twice a week for 10 weeks.
      During the first 6 weeks, both groups used the hypertrophy-type regimen to gain
      muscular size. During the subsequent 4 weeks, HC and HS groups performed combi
      type and strength-type regimens, respectively. Muscular strength, endurance, and
      cross sectional area (CSA) were examined after 2, 6, and 10 weeks. After the
      initial 6 weeks, no significant difference was seen in the percentage changes of
      all variables between the groups. After the subsequent 4 weeks, however, 1RM of
      leg press, maximal isokinetic strength, and muscular endurance of leg extension
      showed significantly (p < 0.05) larger increases in the HC group than in the HS
      group. In addition, increases in CSA after this period also tended to be larger
      in the HC group than in the HS group (p = 0.08). The results suggest that a
      combination of high- and low-intensity regimens is effective for optimizing the
      strength adaptation of muscle in a periodized training program.

PMID- 15574076
TI  - Biochemical and heart adaptations to physical training and supplementation with
      amino acids.
AB  - This study evaluated the role of amino acids supplementation on the heart's
      adaptation under extensive training conditions. Sixty active athletes (bicyclists
      and swimmers) were separated into 2 groups: 30 were given amino acid mixture (1 g
      per 10 kg of body weight) for a period of 1 month, and the other 30 were given
      placebo for the same duration (control group). In the same time period, 20
      subjects of similar age not engaged in physical training or sports activities
      were used as the additional control group. Blood concentrations of alanine
      transaminase (ALT), asparagine transaminase, lactate dehydrogenase (LDH), gamma
      glutamil transpeptidase, alkaline phosphatase (ALP), amylase, triglycerides,
      albumin, interleukin-6 (IL-6), and interleukin-10 (IL-10) were determined for all
      subjects before and after the intervention period. Concentrations of LDH and ALP
      were increased, but concentrations of ALT, albumin, and triglycerides were
      decreased in the blood of trained athletes compared with healthy subjects not
      engaged in sports activities. In the athletes, some increases in IL-6 levels were
      noted; however, they were significantly (p < 0.05) lower than in patients with
      myocardiodystrophy. The values of IL-10 in athletes were higher than
      concentrations of IL-10 in patients with myocardiodystrophy but still lower than
      the normal values. The inhibition of IL-10 in blood may play an important role in
      the induction of apoptosis in cells of the heart muscle. After amino acid
      supplementation, the athletes' values for albumin, triglycerides, IL-10, LDH, and
      ALP were significantly increased compared with the post-placebo control groups.
      Enzyme activities of other enzymes remained unchanged in all groups. Histological
      data from a secondary study of actual heart tissue showed that the amino acids
      supplementation may have inhibiting effects on myocardial apoptosis. The criteria
      of efficiency of the amino acids supplementation were defined by the albumin, IL
      6, and IL-10 concentrations.

PMID- 15574077
TI  - The effect of glycerol on torque, electromyography, and mechanomyography.
AB  - The purpose of this investigation was to determine the effect of hyperhydration
      on the electromyographic (EMG) and mechanomyographic (MMG) responses during
      isometric and isokinetic muscle actions of the biceps brachii. Eight (22.1 +/-
      1.8 years, 79.5 +/- 22.8 kg) subjects were tested for maximal isometric,
      submaximal isometric, and maximal concentric isokinetic muscle strength in either
      a control (C) or hyperhydrated (H) state induced by glycerol ingestion while the
      EMG and MMG signals were recorded. Although fluid retention was significantly
      greater during the H protocol, the analyses indicated no change in torque, EMG
      amplitude, EMG mean power frequency (MPF), MMG amplitude, or MMG MPF with
      hyperhydration. These results indicated that glycerol-induced fluid retention
      does not affect the torque-producing capabilities of a muscle, the impulses (EMG)
      going to a muscle, or muscular vibrations (MMG). It has been suggested that EMG
      and MMG can be used as direct electrical/mechanical monitoring, which could be
      presented to trainers and athletes; however, before determining the utility of
      these signals, the MMG and EMG responses should be examined under a variety of
      conditions such as in the present study.

PMID- 15574078
TI  - Effects of beta-hydroxy beta-methylbutyrate on power performance and indices of
      muscle damage and stress during high-intensity training.
AB  - Twenty-six members of a collegiate football team were randomly assigned to either
      a supplement (S) (3 g of beta-hydroxy beta-methylbutyrate [HMB] per day) or
      placebo (P) group. Testing occurred before (PRE) and at the end of 10 days of
      preseason football training camp (POST). During each testing session, subjects
      performed an anaerobic power test, and blood samples were obtained for
      testosterone, cortisol, creatine kinase, and myoglobin analysis. No differences
      in anaerobic power were seen between PRE and POST in either group. Cortisol
      concentrations were significantly decreased from PRE (333 +/- 81 nmol.L(-1)) to
      POST (246 +/- 79 nmol.L(-1)), and a sixfold increase was seen in creatine kinase
      concentrations at POST. However, no significant differences between the groups
      were seen. No significant time or group effects were observed in testosterone or
      myoglobin concentrations. Results suggest that short duration HMB supplementation
      does not provide any ergogenic benefit in collegiate football players during
      preseason training camp.

PMID- 15574079
TI  - Can albuterol help resistance exercise attenuate unloading-induced bone loss?
AB  - Hind-limb-suspended rats incur attenuated bone loss with beta(2)-agonists, and
      humans note similar changes with concurrent resistance exercise. To examine if
      the beta(2)-agonist albuterol helps resistance exercise reduce unloading-induced
      bone loss, human subjects performed 40 days of unilateral limb suspension with
      their left legs, otherwise refraining from normal ambulatory activity. While
      performing left leg strength training 3 days.week(-1), subjects received a
      concurrent placebo or albuterol (16 mg.day(-1)) treatment. Left leg muscle and
      bone changes were analyzed with 2 x 2 analyses of covariance (ANCOVAs).
      Mechanical loading values were calculated from workouts and compared using a 2 x
      5 analysis of variance (ANOVA) and a Tukey post hoc test. The resistance exercise
      albuterol assignment evoked significant (p < 0.05) left leg bone mineral content
      (BMC) gains (+2.24%) after 40 days. During the final unloading days, the
      resistance exercise-placebo group's mechanical loading data declined (-13.91%)
      significantly (p < 0.05) versus initial values. A resistance exercise-albuterol
      assignment likely increased BMC by maintaining the mechanical loading stimulus.

PMID- 15574080
TI  - Strength/power augmentation subsequent to short-term training abstinence.
AB  - Strength augmentation has been demonstrated in resistance-trained men subsequent
      to 4 days of training abstinence. However, this phenomenon was exhibited in an
      unusual circumstance in which the exercise test (seated heel raise) primarily
      involved an isolated skeletal muscle (soleus) that is normally comprised almost
      exclusively of 1 fiber type. It is unclear if similar results would be found for
      aggregate muscle actions. Therefore, a comparable study was designed with this in
      mind. Subjects were apparently healthy, young, strength-trained men (n = 25). All
      performed various tests of bench press strength at the beginning of their last
      standardized dynamic constant external resistance (DCER) training session.
      Subjects were subsequently randomly assigned to 1 of 4 groups and repeated the
      identical tests at intervals of either 2, 3, 4, or 5 days with no intervening
      training. Strength tests consisted of 1 repetition maximum (1RM) concentric-only
      isokinetic bench presses performed at 1.49 and 0.37 m.s(-1) as well as a 1RM DCER
      bench press. Measures of peak force and power were obtained from the isokinetic
      tests and maximum load from the DCER test. Results were expressed in both
      absolute and relative (to body weight) terms. Subsequent to the 4 abstinence
      intervals, groups performed similarly (p > 0.05) for all dependent variables.
      Concurrently, however, a small effect size (ES) was found for the group having a
      4-day respite for both absolute and relative expressions of peak force and power
      at the slowest isokinetic bench press velocity. A small ES was also identified
      for the group having 2 days of rest for relative peak force at the slowest
      isokinetic test velocity and for relative DCER strength. Therefore, modest and
      transient strength augmentation appears likely in aggregate muscle actions
      following 2-4 days of training abstinence in resistance-trained men, but only at
      relatively slow velocities.

PMID- 15574081
TI  - Effects of muscle damage on stretch-shortening cycle function and muscle
      stiffness control.
AB  - This experiment examined the effect of eccentric contraction-induced muscle
      damage on the stretch-shortening cycle and vertical leg spring stiffness during
      jumping activities. Ten moderately active male and female adult volunteers
      participated in this study (aged 23 +/- 2.3 years). Temporary muscle damage to
      the knee extensors was administered by a bout of eccentric contractions on an
      isokinetic dynamometer. Measurements were obtained of maximum voluntary force and
      of take-off velocities for single-leg countermovement jumps (CMJs), squat jumps
      (SJs), and drop jumps (DJs), performed on a specially constructed sledge and
      force plate apparatus. These measurements were obtained before and after the
      damage intervention, and the undamaged leg was used as a control. The results
      indicated that eccentric muscle damage significantly affected stretch-shortening
      cycle performance by causing relatively greater reductions in SJ performance than
      CMJ or DJ. The muscle damage intervention also significantly increased leg-spring
      stiffness, which indicates that the changes in leg stiffness may be an important
      adaptation resulting from eccentric exercise.

PMID- 15574082
TI  - Effect of vibration during fatiguing resistance exercise on subsequent muscle
      activity during maximal voluntary isometric contractions.
AB  - This investigation was designed to determine if vibration during fatiguing
      resistance exercise would alter associated patterns of muscle activity. A cross
      over design was employed with 8 subjects completing a resistance exercise bout
      once with a vibrating dumbbell (V) (44 Hz, 3 mm displacement) and once without
      vibration (NV). For both exercise bouts, 10 sets were performed with a load that
      induced concentric muscle failure during the 10th repetition. The appropriate
      load for each set was determined during a pretest. Each testing session was
      separated by 1 week. Electromyography (EMG) was obtained from the biceps brachii
      muscle at 12 different time points during a maximum voluntary contraction (MVC)
      at a 170 degrees elbow angle after each set of the dumbbell exercise. The time
      points were as follows: pre (5 minutes before the resistance exercise bout), T1
      T10 (immediately following each set of resistance exercise), and post (15 minutes
      after the resistance exercise bout). EMG was analyzed for median power frequency
      (MPF) and maximum (mEMG). NV resulted in a significant decrease in MPF at T1-T4
      (p < or 0.05) and a significant increase in mEMG at T2 during the MVC. V had an
      overall trend of lower mEMG in comparison to NV. The mEMG and MPF values
      associated with NV were similar to previously reported investigations. The lower
      mEMG values and the higher MPF of V in comparison to NV are undocumented. The EMG
      patterns observed with vibration may indicate a more efficient and effective
      recruitment of high threshold motor units during fatiguing contractions. This may
      indicate the usage of vibration with resistance exercise as an effective tool for
      strength training athletes.

PMID- 15574083
TI  - An investigation of the tri-bar gripping system on isometric muscular endurance.
AB  - Recently, a new product called the Tri-Bar has been introduced as an alternative
      to the standard round weightlifting bar. The Tri-Bar has the same weight, length,
      and circumference as a standard weightlifting bar and differs only in that the
      shape of the bar is formed like a triangle with rounded edges. Theoretically, the
      shape of the bar will enhance gripping comfort and increase muscular endurance.
      We studied 32 moderately trained males who were free from upper-body injury or
      limitation. Each participant completed 4 visits to the lab as part of 2 separate
      investigations. The first investigation was a comparison of straight-arm hang
      times while grasping a standard Olympic bar or a Tri-Bar attached to the top of a
      power rack. The second investigation involved grasping a standard revolving cable
      handle or a Tri-Bar revolving handle attached to a weight equal to half the
      subject's body weight. In both investigations, time was used as a measure of
      isometric muscular endurance. Differences were determined using a dependent t
      test, and a level of significance was set at p < 0.05. Mean hang times were
      significantly longer when the men hung from the Tri-Bar (107.6 seconds) versus
      the standard bar (95.4 seconds) (p = 0.015). Conversely, in the investigation
      using the revolving handles, the round bar produced longer grasping times (71.5
      seconds) than the Tri-Bar (62.6 seconds) (p = 0.000). The results of this
      investigation indicate that a fixed and stable Tri-Bar may help to increase hang
      time, but a Tri-Bar free to rotate within the grasp may decrease grasping time in
      comparison to a standard round handle. With regard to exercises that require
      isometric grasping, the Tri-Bar may be an effective alternative to the standard
      bar for increasing isometric grasping endurance.

PMID- 15574084
TI  - The maximal and submaximal vertical jump: implications for strength and
      conditioning.
AB  - The vertical jump is a widely used activity to develop explosive strength,
      particularly in plyometric and maximal power training programs. It is a
      multijoint action that requires substantial muscular effort from primarily the
      ankle, knee, and hip joints. It is not known if submaximal performances of a
      vertical jump have a proportional or differential training effect on the major
      lower-limb muscles compared to maximal jump performance. Therefore, the purpose
      of this study was to investigate the contribution that each of the major lower
      limb joints makes to vertical jump performance as jump height increases and to
      comment on the previously mentioned uncertainty. Adult males (N = 20) were asked
      to perform a series of submaximal (LOW and HIGH) and maximal (MAX) vertical jumps
      while using an arm swing. Force, motion, and electromyographical data were
      recorded during each performance and used to compute a range of kinematic and
      kinetic data, including ankle, knee, and hip joint torques, powers, and work
      done. It was found that the contribution to jump height made by the ankle and
      knee joints remains largely unchanged as jump height increases (work done at the
      ankle: LOW =1.80, HIGH = 1.97, MAX = 2.06 J.kg(-1), F = 3.596, p = 0.034; knee:
      LOW = 1.62, HIGH = 1.77, MAX = 1.94 J.kg(-1), F = 1.492, p = 0.234) and that
      superior performance in the vertical jump is achieved by a greater effort of the
      hip extensor muscles (work done at the hip: LOW = 1.03, HIGH = 1.84, MAX = 3.24
      J.kg(-1), F = 110.143, p < 0.001). It was concluded that the role of submaximal
      and maximal jumps can be differentiated in terms of their effect on ankle, knee,
      and hip joint muscles and may be of some importance to training regimens in which
      these muscles need to be differentially trained.

PMID- 15574085
TI  - Effect of multiple-load training on the force-velocity relationship.
AB  - The effect of training with a combination of different loads (multiple-load
      training) on the force-velocity and force-power relationships was examined with
      training programs that included maximal isometric contraction (Fmax) and
      concentric contraction of the elbow flexor muscles. Twenty-one male college
      students were placed into 3 equal training groups (G(30 + 60), G(30 + 100), and
      G(30 + 60 + 100)) and performed multiple-load training 3 days per week for 8
      weeks. The training load was a set fraction of the maximal isometric strength (%
      Fmax). The G(30 + 60) group performed 6 repetitions of elbow flexion at 30 and
      60% Fmax. The G(30 + 100) group performed 6 repetitions at 30% Fmax and six 5
      second Fmax loads. The G(30 + 60 + 100) group performed 4 repetitions at 30 and
      60% Fmax and four 5-second Fmax loads. After training, Fmax and maximal velocity
      significantly increased (p < 0.05) in all 3 training groups. The increases in
      maximal power were significantly (p < 0.05) different between the G(30 + 60 +
      100) group (52.9%) and the G(30 + 100) group (24.2%). These results suggest that
      multiple-load training programs with 4-6 repetitions are effective for improving
      muscle power and velocity of the elbow flexors.

PMID- 15574086
TI  - Examination of the scaling of human jumping.
AB  - On the basis of the principles of geometric scaling, maximum vertical-jump height
      should decrease in an approximately linear fashion with increasing mass. To test
      this prediction, a group of 10 male subjects performed maximum vertical jumps
      with masses up to 22.7 kg strapped to their trunks. The results from these jumps
      indicated that jump height did scale on an individual basis in a linear fashion.
      A computer simulation model of jumping was developed that permitted the
      examination of a greater range of masses than was possible experimentally. The
      simulations also support the trend of linear scaling, but do replicate the
      decrement expected based on geometric scaling principles. Experimental and
      simulation model results provide evidence for a linear decrement in subject
      maximum vertical-jump height with increasing mass, which is relevant information
      for athletes aiming to increase their body mass or performing jump training while
      carrying additional mass.

PMID- 15574087
TI  - Comparison of the Wingate and Bosco anaerobic tests.
AB  - The purpose of this study was to compare the Wingate cycling and Bosco repeated
      jumps anaerobic tests. Eleven men (21.36 +/- 1.6 years; 179.1 +/- 9.3 cm; 78.7 +/
      11.0 kg) and 9 women (21.89 +/- 3.66 years; 171.8 +/- 10.0 cm; 75.9 +/- 21.4
      kg), all university athletes, volunteered to participate. Subjects performed each
      test in random order. The tests consisted of a 30-second Wingate test and a 60
      second Bosco test. The Wingate test was conducted using a Monark cycle ergometer
      and the Bosco test was conducted on a force platform. Following the performance
      of each test, peak lactate concentrations were determined. Average and peak power
      values were statistically greater in men and on the Bosco test. Peak lactate
      values were statistically greater in men but did not differ based on test.
      Correlations between peak lactate concentrations between tests and lactate values
      with peak or average power were not statistically significant. The relationship
      between peak power between tests was statistically significant among men, but not
      women. The results of the study indicated that the Bosco and Wingate tests, which
      both measure anaerobic characteristics, appear to measure different aspects of
      anaerobic power and capacity. The Bosco test also may be inappropriate for
      athletes who are not well trained in jumping.

PMID- 15574088
TI  - Effects of standing vs. seated posture on repeated Wingate performance.
AB  - Standing during cycling may increase overall muscular activity. However, effects
      of standing vs. seated posture on performance measures during repeated bouts have
      not been extensively explored. The purpose of this study was to examine the
      effects of standing vs. seated posture on repeated Wingate performance. Healthy
      volunteers (n = 35) performed 3 consecutive Wingate anaerobic power tests (W(1),
      W(2), W(3)) in a standing (STA) as well as seated (SIT) posture. Within-group
      comparisons were made for peak power, mean power, minimum power, and fatigue
      index. Results were considered significant at p < or = 0.05. No significant
      differences were found for peak power in W(1), W(2), or W(3). No significant
      difference was found for mean power in W(1) or W(2), but significant differences
      were found for mean power in W(3) (STA: 451.5 +/- 105.3, SIT: 425.7 +/- 110.0);
      minimum power in W(1) (STA: 433.6 +/- 100.8, SIT: 381.5 +/- 96.9), W(2) (STA:
      348.1 +/- 112.9, SIT: 308.0 +/- 95.8), W(3) (STA: 292.0 +/- 103.6, SIT: 265.3 +/-
      90.8); and fatigue index: W(1) (STA: 51.3 +/- 10.7, SIT: 56.9 +/- 9.3), W(2)
      (STA: 56.5 +/- 12.6, SIT: 61.8 +/- 12.2), W(3) (STA: 59.4 +/- 13.1, SIT: 63.6 +/-
      12.4). Results suggest that a standing posture enhances performance during
      repeated Wingate cycling. The enhancement is most likely due to an attenuated
      loss in power, which in turn improves fatigue index.

PMID- 15574089
TI  - The interval shuttle run test for intermittent sport players: evaluation of
      reliability.
AB  - The reliability of the interval shuttle run test (ISRT) as a submaximal and
      maximal field test to measure intermittent endurance capacity was examined.
      During the ISRT, participants alternately run for 30 seconds and walk for 15
      seconds. The running speed is increased from 10 km.h(-1) every 90 seconds until
      exhaustion. Within a 2-week period, 17 intermittent sport players (i.e., 10 men
      and 7 women) performed the ISRT twice in a sports hall under well-standardized
      conditions. Heart rates per speed and total number of runs were assessed as
      submaximal and maximal performance measures. With the exception of the heart
      rates at 10.0 km.h(-1) for men and 10.0, 12.0, and 13.5 km.h(-1) for women, zero
      lay within the 95% confidence interval of the mean differences, indicating that
      no bias existed between the outcome measures at the 2 test sessions (absolute
      reliability). The results illustrate that it is important to control for heart
      rate before the start of the ISRT. Relative reliability was high (intraclass
      correlation coefficient > or = 0.86). We conclude that the reliability of the
      ISRT as a submaximal and maximal field test for intermittent sport players is
      supported by the results.

PMID- 15574090
TI  - The short-term effect of whole-body vibration training on vertical jump, sprint,
      and agility performance.
AB  - Previous studies have suggested that short-term whole-body vibration (WBV)
      training produces neuromuscular improvement similar to that of power and strength
      training. However, it is yet to be determined whether short-term WBV exposure
      produces neurogenic enhancement for power, speed, and agility. The purpose of
      this study was to investigate the effect short-term WBV training had on vertical
      jump, sprint, and agility performance in nonelite athletes. Twenty-four sport
      science students (16 men and 8 women) were randomly assigned to 2 groups: WBV
      training or control. Each group included 8 men and 4 women. Countermovement jump
      (CMJ) height, squat jump (SJ) height, sprint speed over 5, 10, and 20 m, and
      agility (505, up and back) were performed by each participant before and after 9
      days of either no training (control) or WBV training. Perceived discomfort of
      every participant was recorded after daily WBV exposure and nonexposure. There
      were no significant differences between WBV and control groups for CMJ, SJ,
      sprints, and agility. Perceived discomfort differed between the first and
      subsequent days of WBV training (p < 0.05); however, there was no difference
      between the WBV and control groups. It is concluded that short-term WBV training
      did not enhance performance in nonelite athletes.

PMID- 15574091
TI  - The effect of resistance-training intensity on strength-gain response in the
      older adult.
AB  - This study examined how training intensity affects strength gains in older adults
      over an 18-week training period using nonperiodized, progressive resistance
      training protocols. Untrained men and women participants were separated into 4
      groups: group A (n = 17, 71.4 +/- 4.6 years) performed 2 sets of 15 repetitions
      maximum (RM), group B (n = 13, 71.5 +/- 5.2 years) performed 3 sets of 9 RM,
      group C (n = 17, 69.4 +/- 4.4 years) performed 4 sets of 6 RM, group D (n = 14,
      72.3 +/- 5.9 years) served as controls. Training groups exercised 2 days/week
      performing 8 resistance exercises. Except for training intensity, the acute
      program variables were equated between groups. A 1RM for 8 exercises was obtained
      every 6 weeks. The total of 1RM for the 8 exercises served as the dependent
      variable. RESULTS: repeated measures analysis of variance (ANOVA) and Scheffe
      post hoc revealed that, at 6 weeks, only groups B and C were significantly
      stronger than group D (p < 0.01). By weeks 12 and 18, all training groups were
      significantly stronger than controls (p < 0.01). However, no difference existed
      between groups A, B, and C at any time. The data suggests that, for protocols
      with equated acute program variables, strength gain is similar over 18 weeks for
      training intensities ranging from 6 to 15 RM in previously untrained older
      adults. When programming nonperiodized, progressive resistance exercise for
      novice senior lifters, in the initial phases of the program, a wide range of
      intensities may be employed with similar strength gain.

PMID- 15574092
TI  - Comparing the performance-enhancing effects of squats on a vibration platform
      with conventional squats in recreationally resistance-trained men.
AB  - The purpose of this investigation was to compare the performance-enhancing
      effects of squats on a vibration platform with conventional squats in
      recreationally resistance-trained men. The subjects were 14 recreationally
      resistance-trained men (age, 21-40 years) and the intervention period consisted
      of 5 weeks. After the initial testing, subjects were randomly assigned to either
      the "squat whole body vibration" (SWBV) group (n = 7), which performed squats on
      a vibration platform on a Smith Machine, or the "squat"(S) group (n = 7), which
      performed conventional squats with no vibrations on a Smith Machine. Testing was
      performed at the beginning and the end of the study and consisted of 1 repetition
      maximum (1RM) in squat and maximum jump height in countermovement jump (CMJ). A
      modified daily undulating periodization program was used during the intervention
      period in both groups. Both groups trained at the same percentage of 1RM in
      squats (6-10RM). After the intervention, CMJ performance increased significantly
      only in the SWBV (p < 0.01), but there was no significant difference between
      groups in relative jump height increase (p = 0.088). Both groups showed
      significant increases in 1RM performance in squats (p < 0.01). Although there was
      a trend toward a greater relative strength increase in the SWBV group, it did not
      reach a significant level. In conclusion, the preliminary results of this study
      point toward a tendency of superiority of squats performed on a vibration
      platform compared with squats without vibrations regarding maximal strength and
      explosive power as long as the external load is similar in recreationally
      resistance-trained men.

PMID- 15574093
TI  - The effects of varied rest periods between sets to failure using the bench press
      in recreationally trained men.
AB  - The purpose of this study was to determine the rate of recovery for recreational
      weight trainers between 2 sets of bench press to volitional exhaustion. Twenty
      eight men performed 2 sets of the bench press at 75% of their previously
      determined 1 repetition maximum (1RM) to volitional exhaustion. Rest periods of
      1, 3, or 5 minutes between sets were utilized on the 3 separate testing days.
      There was a significant decrease in the number of repetitions performed between
      the second sets at all rest periods. There were no significant differences in
      work performed (repetitions x weight) during the second set with the 3- and 5
      minute rest periods, but the total work with a 1-minute rest period (1,389.1 +/-
      529.9) was significantly less than both the 3- (1,494.9 +/- 451.0) and 5-minute
      (1,711.4 +/- 478.0) rest period. The data indicated that subjects were unable to
      fully recover between the first and second sets of maximal resistance exercise,
      regardless of the rest period. However, subjects were able to maintain a
      performance level of 8-12 repetitions and sustain the total work performed per
      set with as little as 3 minutes rest between sets.

PMID- 15574094
TI  - Isokinetic profile of shoulder internal and external rotators of high school aged
      baseball pitchers.
AB  - The purpose of this descriptive study was to determine whether bilateral
      differences exist in concentric and eccentric shoulder internal and external
      rotation strength in high school aged baseball pitchers. Thirty-nine high school
      aged baseball pitchers were bilaterally tested for concentric and eccentric
      internal and external rotation muscle performance on a Kin-Com 500-H isokinetic
      dynamometer at 90 degrees .s(-1) and 180 degrees .s(-1). Paired t-tests were used
      to test for differences among extremities, speed, and ratio of external rotation
      to internal rotation (ER/IR ratios). Concentric peak torque internal rotation at
      90 degrees .s(-1) was significantly greater (p < 0.05) in the dominant arm
      compared with the nondominant arm. Statistically significant differences (p <
      0.001) were found between the nondominant and dominant in concentric 90 degrees
      .s(-1). The nondominant arm demonstrated significantly greater eccentric strength
      (p < 0.05) compared with the dominant arm in ER/IR ratios at 90 degrees .s(-1)
      and 180 degrees .s(-1). The nondominant arm demonstrated significantly greater
      eccentric strength (p < 0.05) than the dominant arm in ER/IR ratio at 180 degrees
      .s(-1). Data demonstrated that muscular adaptations are consistent with previous
      research in this area. Also, muscular adaptations occur in the shoulder in the
      high school aged population. These data can serve as a guideline to be used by
      clinicians who rehabilitate shoulders in patients in this population.

PMID- 15574095
TI  - Relationships between isokinetic knee strength, single-sprint performance, and
      repeated-sprint ability in football players.
AB  - Previous research has demonstrated that muscular strength of the knee extensors
      is related to the speed an athlete can produce during a single-sprint
      performance. Football players, as well as many other athletes on the field and
      the court, execute multiple sprints during the course of a match. The purpose of
      this study was to examine the relationships between leg strength, single-sprint
      speed, and repeated-sprint ability. Thirty-eight football players from 3 codes
      (soccer, rugby league, rugby union) completed a 12- x 20-m repeated-sprint
      protocol and were evaluated for peak isokinetic knee extension and flexion torque
      at 60 degrees .s(-1), 150 degrees .s(-1), and 240 degrees .s(-1). Although single
      sprint performance correlated with peak extensor and flexor torque at all
      velocities, the strongest correlation was observed between relative knee extensor
      torque at 240 degrees .s(-1) and the initial acceleration phase (0-10 m) of the
      single-sprint performance (r = -0.714, p < 0.01). However, the data suggest that
      factors other than strength contribute to repeated-sprint ability. This finding
      provides new evidence in elucidating the relationship between strength and
      repeated-sprint performance.

PMID- 15574096
TI  - Physical activity and its relationship to rodeo injury and success.
AB  - The purpose of this study was to determine the interrelationship among physical
      activity, injury, and success of rodeo athletes. Seventy-two male Professional
      Rodeo Cowboys' Association members served as participants and were grouped into
      timed, steer-wrestling, saddle-bronc, bareback, bull-riding, and multiple rough
      stock events. Participants completed demographic and overall physical activity
      questionnaires. Sixty-two percent of the subjects participated in regular
      exercise for a minimum of 2 days per week. Pearson bivariate correlation
      coefficients revealed weak correlations (r = 0.151, -0.188, and -0.074; p > 0.05)
      among metabolic (MET) level, earnings rate, and injury rate. A 1-way between
      subjects analysis of variance indicated no differences in MET level among groups.
      Physical activity did not affect performance or injury rate, and competitors in
      various events did not have different levels of energy expenditure. Therefore,
      rodeo sports-medicine personnel should encourage athletes to engage in other
      sport-specific training activities to help prevent rodeo injuries.

PMID- 15574097
TI  - The importance of isometric maximum strength and peak rate-of-force development
      in sprint cycling.
AB  - This study was designed to investigate the relationship of whole-body maximum
      strength to variables potentially associated with track sprint-cycling success.
      These variables included body composition, power measures, coach's rank, and
      sprint-cycling times. The study was carried out in 2 parts. The first part (n =
      30) served as a pilot for the second part (n = 20). Subjects for both parts
      ranged from international-caliber sprint cyclists to local-level cyclists.
      Maximum strength was measured using an isometric midthigh pull (IPF). Explosive
      strength was measured as the peak rate-of-force development (IPRFD) from the
      isometric force-time curve. Peak power was estimated from countermovement (CMJPP)
      and static vertical jumps (SJPP) and measured by modified Wingate tests. Athletes
      were ranked by the U.S. national cycling coach (part 1). Sprint times (from a
      standing start) were measured using timing gates placed at 25, 82.5, 165, 247.5,
      and 330 m of an outdoor velodrome (part 2). Maximum strength (both absolute and
      body-mass corrected) and explosive strength were shown to be strongly correlated
      with jump and Wingate power. Additionally, maximum strength was strongly
      correlated with both coach's rank (parts 1 and 2) and sprint cycling times (part
      2). The results suggest that larger, stronger sprint cyclists have an advantage
      in producing power and are generally faster sprint cyclists.

PMID- 15574098
TI  - The effect of different warm-up stretch protocols on 20 meter sprint performance
      in trained rugby union players.
AB  - The purpose of this study was to determine the effect of different static and
      dynamic stretch protocols on 20-m sprint performance. The 97 male rugby union
      players were assigned randomly to 4 groups: passive static stretch (PSS; n = 28),
      active dynamic stretch (ADS; n = 22), active static stretch (ASST; n = 24), and
      static dynamic stretch (SDS; n = 23). All groups performed a standard 10-minute
      jog warm-up, followed by two 20-m sprints. The 20-m sprints were then repeated
      after subjects had performed different stretch protocols. The PSS and ASST groups
      had a significant increase in sprint time (p < or = 0.05), while the ADS group
      had a significant decrease in sprint time (p < or = 0.05). The decrease in sprint
      time, observed in the SDS group, was found to be nonsignificant (p > or = 0.05).
      The decrease in performance for the 2 static stretch groups was attributed to an
      increase in the musculotendinous unit (MTU) compliance, leading to a decrease in
      the MTU ability to store elastic energy in its eccentric phase. The reason why
      the ADS group improved performance is less clear, but could be linked to the
      rehearsal of specific movement patterns, which may help increase coordination of
      subsequent movement. It was concluded that static stretching as part of a warm-up
      may decrease short sprint performance, whereas active dynamic stretching seems to
      increase 20-m sprint performance.

PMID- 15574099
TI  - Strength and conditioning practices of National Hockey League strength and
      conditioning coaches.
AB  - This study describes the results of a survey of the practices of National Hockey
      League strength and conditioning (NHL S&C) coaches. The response rate was 76.6%
      (23 of 30). This survey examines (a) background information, (b) physical
      testing, (c) flexibility development, (d) speed development, (e) plyometrics, (f)
      strength/power development, (g) unique aspects, and (h) comments. Results
      indicate, in part, that coaches assess an average of 7.2 parameters of fitness,
      with tests of strength and power being the most common. All coaches used a
      variety of flexibility-development strategies. Results reveal that 21 of 23
      (91.3%) of NHL S&C coaches follow a periodization model (PM). Of the coaches who
      follow a PM, 21 of 21 (100%) indicated that their athletes used Olympic-style
      lifts, and 21 of 21 coaches (100%) trained athletes with plyometric exercises.
      For those who used plyometrics with their athletes, 17 of 21 (80.1%) reported no
      plyometric-related injuries in the past year. Coaches who report they did not
      follow a PM also did not use Olympic-style lifts, plyometrics, or speed
      development strategies, such as assisted, resisted, or interval training, with
      their athletes. Finally, coaches reported that the squat and their variations, as
      well at the Olympic-style lifts and its variations, were most frequently used
      with their athletes. The survey serves as a review, as well as a source of
      applied information and new ideas.

PMID- 15574100
TI  - Anabolic steroid usage in athletics: facts, fiction, and public relations.
AB  - Anecdotal evidence suggests the widespread usage of anabolic steroids among
      athletes (20-90%), particularly at the professional and elite amateur levels. In
      contrast, scientific studies indicate that usage is rare and no higher than 6%.
      Conclusions from scientific studies suggest that anabolic steroid usage declines
      progressively from high school to college and beyond; however, anecdotal evidence
      claims the opposite trend. In this clash between "hard" scientific data vs.
      "soft" anecdotal information, it is natural that professionals would gravitate
      toward scientifically based conclusions. However, in the case of anabolic
      steroids (a stigmatized and illegal substance), should word-of-mouth testimony
      from individuals closest to the issues--those who have participated in and
      coached sports, those who have served as drug-testing overseers, and journalists
      who relentlessly track leads and verify sources--be set aside as irrelevant? Not
      if a complete picture is to emerge. In this review, hard scientific evidence is
      placed on the table side-by-side with soft anecdotal evidence, without weighting
      or bias. The purpose is to allow the opportunity for each to illuminate the other
      and, in so doing, potentially bring us a step closer to determining the true
      extent of anabolic steroid usage in athletics.

PMID- 15574101
TI  - Determining the magnitude of treatment effects in strength training research
      through the use of the effect size.
AB  - In order to improve the applicability of research to exercise professionals, it
      is suggested that researchers analyze and report data in intervention studies
      that can be interpreted in relation to other studies. The effect size and
      proposed scale for determining the magnitude of the treatment effect can assist
      strength and conditioning professionals in interpreting and applying the findings
      of the strength training studies.

PMID- 15574102
TI  - Synthesizing strength and conditioning research: the meta-analysis.
AB  - As the body of research examining strength and conditioning topics grows, it is
      vital that researchers be able to effectively synthesize research findings. The
      meta-analysis has been shown to be a more advanced form of research synthesis
      than the conventional narrative review. Meta-analytic procedures are discussed
      and applications to strength related research are presented.

PMID- 15574103
TI  - Cardiovascular responses to a high-volume continuous circuit resistance training
      protocol.
AB  - The purpose of this investigation was to determine the level of cardiovascular
      stress elicited by continuous and prolonged circuit resistance training (CRT).
      Each of the 11 men who volunteered as a subject were tested to determine oxygen
      consumption and heart rate responses to a submaximal and maximal treadmill
      protocol and a CRT session consisting of 10 exercises and 10 repetitions at 40%
      of 1 repetition maximum (1RM) for each station with 4.6 circuits performed. The
      physiological stress of the CRT in this study was evident by the sustained heart
      rate of more than 70% of maximum for 16.6 minutes, with the last 12 minutes at
      more than 80%. Despite the large anaerobic component in CRT, Vo(2) was sustained
      at 50% or more of maximum for the final 12 minutes. Treadmill running, involving
      large muscle groups, increased Vo(2) more rapidly than CRT, where alternating
      larger and smaller muscle groups were used. In addition, at the same Vo(2) heart
      rate differed significantly between the 2 modes of activity. Heart rate in CRT
      was higher (at 165) than the heart rate of 150 found during treadmill running at
      the same 50% Vo(2). Such workouts may be used in a training cycle in classical
      linear periodization or in a nonlinear program day targeting local muscular
      endurance under intense cardiorespiratory conditions, which may help individuals
      develop enhanced toleration of physiological environments where high
      cardiovascular demands and higher lactate concentrations are present.

PMID- 15574104
TI  - Quantitation of resistance training using the session rating of perceived
      exertion method.
AB  - The purpose of this study was to apply the session rating of perceived exertion
      (RPE) method, which is known to work with aerobic training, to resistance
      training. Ten men (26.1 +/- 10.2 years) and 10 women (22.2 +/- 1.8 years),
      habituated to both aerobic and resistance training, performed 3 x 30 minutes
      aerobic training bouts on the cycle ergometer at intensities of 56%, 71%, and 83%
      Vo(2) peak and then rated the global intensity using the session RPE technique
      (e.g., 0-10) 30 minutes after the end of the session. They also performed 3 x 30
      minutes resistance exercise bouts with 2 sets of 6 exercises at 50% (15
      repetitions), 70% (10 repetitions), and 90% (4 repetitions) of 1 repetition
      maximum (1RM). After each set the exercisers rated the intensity of that exercise
      using the RPE scale. Thirty minutes after the end of the bout they rated the
      intensity of the whole session and of only the lifting components of the session,
      using the session RPE method. The rated intensity of exercise increased with the
      %Vo(2) peak and the %1RM. There was a general correspondence between the relative
      intensity (%Vo(2) peak and % 1RM) and the session RPE. Between different types of
      resistance exercise at the same relative intensity, the average RPE after each
      lift varied widely. The resistance training session RPE increased as the
      intensity increased despite a decrease in the total work performed (p < 0.05).
      Mean RPE and session RPE-lifting only also grew with increased intensity (p <
      0.05). In many cases, the mean RPE, session RPE, and session RPE- lifting only
      measurements were different at given exercise intensities (p < 0.05). The session
      RPE appears to be a viable method for quantitating the intensity of resistance
      training, generally comparable to aerobic training. However, the session RPE may
      meaningfully underestimate the average intensity rated immediately after each
      set.

PMID- 15574105
TI  - Changes in physical fitness parameters during a competitive field hockey season.
AB  - Competitive field hockey requires a substantial amount of muscular strength,
      speed, and cardiovascular endurance. It is unknown how these parameters of
      physical fitness change between preseason conditioning to postseason recovery.
      Therefore, Division III female field hockey athletes (n = 13) completed tests of
      muscular strength, body composition, and maximal oxygen uptake (Vo(2)max) during
      each phase of their season. Muscular strength was assessed using 1 repetition
      maximum (RM) leg and bench press tests. Body composition was assessed by
      anthropometry (skinfolds [SKF]), circumferences ([CC]), and bioelectrical
      impedance analysis (BIA). Incremental treadmill testing was administered to
      assess Vo(2)max. Vo(2)max was unchanged during the season, although a trend (p >
      0.05) was shown for a higher Vo(2)max during and after the season vs. before the
      season. Upper- (10%) and lower-body strength (14%) decreased (p > 0.05) during
      the season. Percent body fat (%BF) from BIA, fat mass (FM) from CC, and body mass
      index (BMI) were significantly lower (p < 0.05) in-season and postseason vs.
      preseason. In conclusion, preseason training was effective in decreasing %BF and
      increasing Vo(2)max, yet muscular strength was lost. Coaches should incorporate
      more rigorous in-season resistance training to prevent strength decrements.
      Moreover, these data support the superior levels of muscular strength and
      leanness in these athletes compared with age-matched peers.

PMID- 15574106
TI  - Effect of selected recovery conditions on performance of repeated bouts of
      intermittent cycling separated by 24 hours.
AB  - The purpose of this study was to examine the effects of active recovery (AR),
      massage (MR), and cold water immersion (CR) on performance of repeated bouts of
      high-intensity cycling separated by 24 hours. For each recovery condition,
      subjects were asked to take part in 2 intermittent cycling sessions; 18 minutes
      of varying work intervals performed in succession at a resistance of 80 g/kg body
      weight separated by 24 hours. One of four 15-minute recovery conditions
      immediately followed the first session and included: (a) AR, cycling at 30%
      Vo(2)max; (b) CR, immersion of legs in a 15 degrees C water bath; (c) MR, massage
      of the legs; and (d) control, seated rest. Only the control condition showed a
      significant decline in the total work completed between the first and second
      exercise sessions (108.1 +/- 5.4 kJ vs. 106.0 +/- 5.0 kJ, p < 0.05). Thus, AR,
      MR, and CR appeared to facilitate the recovery process between 2 high-intensity,
      intermittent exercise sessions separated by 24 hours.

PMID- 15574107
TI  - Physical fitness profile of Army ROTC cadets.
AB  - One role of Army Reserved Officer's Training Corps (ROTC) programs is to
      physically prepare cadets for the demands of a military career. Cadets
      participate in physical training 3 days per week as part of their military
      science curriculum. Limited research has been conducted on the fitness level of
      ROTC cadets; therefore, the purpose of this study was to profile the physical
      fitness status of a cadre of ROTC cadets. Forty-three cadets (30 men and 13
      women) performed Army Physical Fitness Test (APFT) assessments (2-mile run, 2
      minute maximum push-ups and sit-ups) and clinical assessments of fitness (Bruce
      protocol Vo(2)max, underwater weighing, and 1 repetition maximum [1RM] bench
      press tests). Mean +/- standard deviations were calculated to provide the
      physical fitness profile for each parameter. Male cadets (21 +/- 2.2 years;
      height 177.4 +/- 6.6 cm; mass 79.2 +/- 9.4 kg) scored 49.6 +/- 6.1 ml.kg(-1).min(
      1) for Vo(2)max, 14.8 +/- 4.2% fat, 86.5 +/- 24.9 kg 1RM bench press, 2-mile run
      of 13.97 +/- 1.4 minutes, 70.5 +/- 12.8 sit-ups, and 60.2 +/- 13.2 push-ups.
      Female cadets (20 +/- 2.4 years; height 165.1 +/- 8.0 cm; mass 63.5 +/- 10.0 kg)
      scored 40.8 +/- 3.9 ml.kg(-1).min(-1) for Vo(2) max, 23.9 +/- 3.8% fat, 35.3 +/-
      8.2 kg 1RM bench press, 2-mile run of 17.0 +/- 1.6 minutes, 65.0 +/- 12.9 sit
      ups, and 33.3 +/- 11.2 push-ups. The mean scores were above the 83rd percentile
      on all APFT items and average (percent fat) to above average (Vo(2)max and men's
      bench press scores) when compared with peer-age and sex-corrected norms. Only the
      women's bench press score was below average. With the exception of the women's
      bench press, these ROTC cadets possessed average to above average levels of
      fitness.

PMID- 15574108
TI  - Publish or be damned.

PMID- 15574109
TI  - A systematic review of efficacy of McKenzie therapy for spinal pain.
AB  - A systematic review of randomised clinical trials was conducted to investigate
      the efficacy of McKenzie therapy in the treatment of spinal pain. Databases
      searched included DARE, CINAHL, CENTRAL, EMBASE, MEDLINE and PEDro. To be
      eligible for inclusion trials had to provide treatment according to McKenzie
      principles and report on one of the following outcomes: pain, disability, quality
      of life, work status, global perceived effect, medication use, health care
      contacts, or recurrence. Six trials were found to be eligible, all comparing
      McKenzie therapy to a comparison treatment. These included NSAIDS, educational
      booklet, back massage and back care advice, strength training, and spinal
      mobilisation and general exercises. The data from five lumbar trials were pooled
      at short term (less than three months) and from three at intermediate (3-12
      months) follow-up. At short term follow-up the McKenzie therapy provided a mean
      8.6 point greater pain reduction on a 0 to 100 point scale (95% CI 3.5 to 13.7)
      and a 5.4 point greater reduction in disability on a 0 to 100 point scale (95% CI
      2.4 to 8.4) than comparison. At intermediate follow-up, relative risk of work
      absence was 0.81 (0.46 to 1.44) favouring McKenzie, however the comparison
      treatments provided a 1.2 point greater disability reduction (95% CI -2.0 to
      4.5). In the one cervical trial, McKenzie therapy provided similar benefits to an
      exercise program. The results of this review show that for low back pain patients
      McKenzie therapy does result in a greater decrease in pain and disability in the
      short term than other standard therapies. Making a firm conclusion on low back
      pain treatment effectiveness is difficult because there are insufficient data on
      long term effects on outcomes other than pain and disability, and no trial has
      yet compared McKenzie to placebo or no treatment. There are also insufficient
      data available on neck pain patients.

PMID- 15574110
TI  - Additional task-related practice improves mobility and upper limb function early
      after stroke: a randomised controlled trial.
AB  - The purpose of this study was to investigate whether additional practice of
      either upper limb or mobility tasks improved functional outcome during inpatient
      stroke rehabilitation. This prospective, randomised, single blind clinical trial
      recruited 30 stroke subjects into either an Upper Limb or a Mobility Group. All
      subjects received their usual rehabilitation and an additional session of task
      related practice using a circuit class format. Independent assessors, blinded to
      group allocation, tested all subjects. Outcome measures used were three items of
      the Jebsen Taylor Hand Function Test (JTHFT), two arm items of the Motor
      Assessment Scale (MAS), and three mobility measures, the Timed Up and Go Test
      (TUGT), Step Test, and Six Minute Walk Test (6MWT). Both groups improved
      significantly between pre- and post-tests on all of the mobility measures,
      however only the Upper Limb Group made a significant improvement on the JTHFT and
      MAS upper arm items. Following four weeks training, the Mobility Group had better
      locomotor ability than the Upper Limb Group (between-group differences in the
      6MWT of 116.4 m, 95% CI 31.4 to 201.3 m, Step Test 2.6 repetitions, 95% CI -1.0
      to 6.2 repetitions, and TUGT -7.6 sec, 95% CI -15.5 to 0.2 sec). The JTHFT
      dexterity scores in the Upper Limb Group were 6.5 sec (95% CI -7.4 to 20.4 sec)
      faster than the Mobility Group. Our findings support the use of additional task
      related practice during inpatient stroke rehabilitation. The circuit class format
      was a practical and effective means to provide supervised additional practice
      that led to significant and meaningful functional gains.

PMID- 15574111
TI  - Patients' experiences of readiness for discharge following a total hip
      replacement.
AB  - In recent years there has been a reduction in the length of stay of patients
      undergoing total hip replacement, as hospitals have attempted to reduce costs. A
      reduced length of stay requires patients undergoing total hip replacement to
      achieve independence over increasingly shorter periods. Clinical experience
      indicates that many of these patients feel unready or reluctant to be discharged
      to home, even though they are physically capable. Information is required about
      psychosocial factors that may affect or delay discharge. This naturalistic study
      used grounded theory methodology to explore the perceptions of discharge
      readiness of people who had undergone a total hip replacement. Using purposive
      sampling, five participants were interviewed prior to discharge from an acute
      hospital. The analysis resulted in the emergence of three categories:
      'Confidence', 'Family and friends', and 'Feeling safe'. Participants wanted to
      feel safe both in the hospital and at home. Their own confidence levels and the
      presence of family and friends at home had a strong influence on feelings of
      safety. The core category and main concern of participants appeared to be about
      feeling safe. Participants who felt safe perceived they were ready to be
      discharged. Healthcare professionals can recognise and question patients about
      some of these factors that influence feelings of safety and readiness for
      discharge. Recognising concerns of patients prior to discharge will promote good
      patient care and discharge planning that is more acceptable to patients and
      carers.

PMID- 15574112
TI  - Physiological quadriceps lag: its nature and clinical significance.
AB  - A study of the limit of active and passive knee extension in 64 healthy adults
      revealed a physiological quadriceps lag; that is, in most subjects the active
      limit of knee extension fell short of the passive limit. With the subjects
      seated, for the passive test the examiner lifted the heel until the relaxed knee
      sagged into full extension under its own weight. The active test component
      comprised maximum active extension held for at least 5 sec. Videotaped reference
      markers on the lateral aspect of the limb were computer-analysed to derive the
      active and passive test positions. The active limit of knee extension was less
      than the passive limit by an average 2.5 degrees at the instant of maximum active
      knee extension, and by 2.9, 3.5, 4.0, 4.5 and 5.0 degrees 1, 2, 3, 4 and 5 sec
      later. At 0 and 5 sec, 16% and 41% of the subjects manifested a quadriceps lag of
      at least 5 degrees. There was no correlation between the magnitudes of passive
      knee extension and quadriceps lag. Since clinicians typically take several
      seconds to estimate visually or otherwise measure knee extension, account should
      be taken of the duration of maximum active contraction, as well as other details
      of test methodology, if quadriceps lag tests are to produce valid and reliable
      results.

PMID- 15574113
TI  - Clinical education of physiotherapy students in Australia: perceptions of current
      models.
AB  - The aim of this study was to seek opinions regarding the perceived advantages and
      disadvantages of the two main models of clinical education used in Australia. A
      questionnaire was designed specifically for this study and distributed to
      physiotherapists involved in clinical education at health units throughout
      Australia. There were 343 respondents (giving an approximate response rate of
      74.5%). In most health units (78.4%) the model of clinical education currently
      used involves a number of physiotherapists sharing responsibility for the
      clinical education of students (SR model). Only a minority reported employing a
      designated clinical educator (DCE) to provide clinical education. Overall,
      respondents preferred the DCE model to the SR model. The perceived advantages of
      the DCE model included an increased time to devote to clinical education,
      improved consistency of supervision and decreased stress levels for staff.

PMID- 15574114
TI  - The Timed Up and Go Test: unable to predict falls on the acute medical ward.
AB  - Prevention of falls amongst older people is a high priority in health care. The
      aim of this study was to evaluate the ability of the Timed Up and Go Test to
      predict those older people who will fall whilst admitted to an acute hospital.
      The medical records of 160 older patients who were admitted to the medical ward
      of a large regional hospital were accessed retrospectively. The Timed Up and Go
      Test, used in isolation, was unable to identify those patients who were likely to
      fall. However the co-morbidity of incontinence was identified as a falls risk
      factor (OR = 8.7, p = 0.001). The Timed Up and Go Test alone does not possess
      predictive validity for acutely unwell older patients. It is therefore
      recommended that it not be used to identify those people who may fall.

PMID- 15574116
TI  - ACOPRA does not have a requirement for 1000 hours of supervised clinical
      experience in entry level physiotherapy programs.

PMID- 15574117
TI  - Internalization and trafficking of guanylyl (guanylate) cyclase/natriuretic
      peptide receptor A is regulated by an acidic tyrosine-based cytoplasmic motif
      GDAY.
AB  - We have identified a GDAY motif in the C-terminal domain of guanylyl cyclase
      (guanylate cyclase)/NPRA (natriuretic peptide receptor A) sequence, which serves
      a dual role as an internalization signal and a recycling signal. To delineate the
      role of the GDAY motif in receptor internalization and sequestration, we mutated
      Gly920, Asp921 and Tyr923 to alanine residues (GDAY/AAAA) in the NPRA cDNA
      sequence. The cDNAs encoding wild-type and mutant receptors were transfected in
      HEK-293 cells (human embryonic kidney 293 cells). The internalization studies of
      ligand-receptor complexes revealed that endocytosis of 125I-ANP by HEK-293 cells
      expressing G920A, Y923A or GDAY/AAAA mutant receptor was decreased by almost 50%
      (P<0.001) when compared with cells expressing the wild-type receptor. However,
      the effect of D921A mutation on receptor internalization was minimal. Ligand
      mediated down-regulation of G920A, Y923A and GDAY/AAAA mutant receptors was
      decreased by 35-40% when compared with wild-type NPRA. Subsequently, the
      recycling of internalized D921A and GDAY/AAAA mutant receptors from the
      intracellular pool was decreased by more than 40+/-4% when compared with wild
      type NPRA. Recycling of G920A and Y923A mutant receptors was also decreased, but
      to a significantly lesser extent compared with the D921A or GDAY/AAAA mutant
      receptors. We conclude that the Gly920 and Tyr923 residues within the GDAY
      consensus motif are necessary for internalization, and that residue Asp921 is
      important for recycling of NPRA. The current results provide new evidence for a
      dual role of the GDAY sequence motif in ligand-mediated internalization,
      recycling and down-regulation of a single-transmembrane receptor protein NPRA.

PMID- 15574118
TI  - Fed-batch pediocin production by Pediococcus acidilactici NRRL B-5627 on whey.
AB  - Cell growth and pediocin production by Pediococcus acidilactici NRRL B-5627 on
      whey were compared by using batch fermentation and re-alkalized fed-batch
      fermentation. The batch fermentations were performed on DWG [DW (diluted whey)
      supplemented with 1% (w/v) glucose], DWYE [DW supplemented with 2% (w/v) yeast
      extract] and DWGYE (DW supplemented with 1% glucose plus 2% yeast extract) media.
      The fed-batch culture on DWYE medium was fed with a mixture of concentrated whey
      (48 g of total sugars/l) supplemented with 2% yeast extract and 400 g/l
      concentrated glucose. The re-alkalized fed-batch culture was characterized by
      higher biomass (6.57 g/l) and pediocin [517.6 BU (bacteriocin activity units)/ml]
      concentrations compared with the batch processes on MRS (de Man, Rogosa and
      Sharpe) broth (1.76 g/l and 493.2 BU/ml), DW (0.17 g/l and 57.7 BU/ml), DWG (0.14
      g/l and 53.6 BU/ml), DWYE (1.43 g/l and 187.6 BU/ml) and DWGYE (1.28 g/l and
      167.3 BU/ml) media. A mixed acid fermentation was observed during the growth of
      P. acidilactici NRRL B-5627 in the fed-batch culture on DWYE medium, and other
      products (acetic acid and ethanol) in addition to lactic acid accumulated in the
      medium. Mathematical models were set up to describe fed-batch production of
      biomass and pediocin by P. acidilactici. The models developed offer a better fit
      and a more realistic description of the experimental biomass and pediocin
      production data when compared with the logistic and Luedeking and Piret model.

PMID- 15574119
TI  - Change in beta1-adrenergic receptor protein concentration in adipose tissue
      correlates with diet-induced weight loss.
AB  - The aim of the present study was to examine gene expression and protein
      concentrations of beta(1)- and beta(2)-adrenergic receptors in subcutaneous
      adipose tissue in obese subjects in response to weight loss. Eighteen obese
      subjects were studied during diet-induced weight loss. Beta-adrenergic receptor
      mRNA levels were quantified by reverse transcription-PCR-HPLC. Beta-adrenergic
      receptor protein concentrations were measured by Western blotting using
      fluorescence laser scanning for detection. Subjects lost 12.8+/-0.8 kg (mean+/
      S.E.M.) during diet treatment. There was a 34% decrease in the beta(1)-adrenergic
      receptor mRNA level (0.92+/-0.09 compared with 0.61+/-0.06 amol/microg of DNA;
      P<0.002). Beta(2)-adrenergic receptor mRNA did not decrease significantly.
      Beta(2)-adrenergic receptor protein concentration decreased 37% (25.5+/-7.1
      compared with 16.0+/-5.6 arbitrary units/ng of DNA; P=0.008), whereas beta(1)
      adrenergic receptor protein concentration did not decrease significantly. The
      degree of weight loss was correlated with the concentration of beta(1)-adrenergic
      receptor protein (r=0.65, P<0.003) and changes in receptor protein concentration
      (r=0.50, P=0.035) during the very-low-calorie diet. In conclusion, the present
      study demonstrates a relationship between beta(1)-adrenergic receptor protein
      concentration in adipose tissue and the degree of weight loss. This relationship
      is not directly related to energy expenditure and deserves further investigation.

PMID- 15574120
TI  - Immunomodulatory and antitumour effects of an exopolysaccharide fraction from
      cultivated Cordyceps sinensis (Chinese caterpillar fungus) on tumour-bearing
      mice.
AB  - Cordyceps sinensis (Chinese caterpillar fungus) is a fungus parasitic on the
      larvae of Lepidoptera and has been considered to be a precious tonic food and
      herbal medicine since ancient times in China. Recently, some fungal strains have
      been isolated from the fruiting bodies of wild C. sinensis, and some of them have
      been reported to show the same properties as the natural product. In the present
      study, an EPSF (exopolysaccharide fraction) was prepared from cultivated C.
      sinensis and its effects on B16 melanoma-bearing mice were investigated. Three
      doses of EPSF were intraperitoneally administered every 2 days after the day of
      tumour-cell injection. The experiment was terminated on day 28. Phagocytosis of
      peritoneal macrophages and proliferation of spleen and thymus lymphocytes were
      assayed. The tumour metastatic foci on the lung and liver surface were checked.
      The expression of oncoprotein Bcl-2 in livers and lungs was assayed by a
      immunohistochemical method. The results showed that EPSF significantly enhanced
      the Neutral Red uptake capacity of peritoneal macrophages (60 mg/kg, P<0.01; 120
      mg/kg, P<0.001) and spleen lymphocyte proliferation (60 mg/kg, P<0.05; 120 mg/kg,
      P<0.001) in B16-bearing mouse. The metastasis of B16 melanoma cells to lungs (120
      mg/kg) and livers (30, 60 and 120 mg/kg) was significantly inhibited by EPSF.
      Moreover, EPSF decreased the levels of Bcl-2 in the lungs (120 mg/kg) and livers
      (30, 60 and 120 mg/kg). These results suggest that EPSF has immunomodulatory
      function and antitumour activity.

PMID- 15574121
TI  - Characterization of a new family of cyclin-dependent kinase activators.
AB  - Progression through the cell cycle is regulated by CDKs (cyclin-dependent
      kinases), which associate with activating partners, named cyclins, to efficiently
      phosphorylate substrates. We previously reported the identification of RINGO, a
      Xenopus protein that can activate CDK1 and CDK2 despite lack of sequence
      similarity to cyclins, which plays a role in the regulation of the meiotic cell
      cycle in oocytes. In the present study we report the characterization of four
      mammalian RINGO proteins, which are 53-68% identical with Xenopus RINGO in a
      central core of about 75 residues. We show that all RINGO family members can bind
      to and activate CDK1 and CDK2, albeit with different efficiencies, but they do
      not bind to CDK4 or CDK6. The core RINGO sequences are critical for CDK
      activation. We also identified key residues in CDK2 that are required for RINGO
      binding. All RINGO proteins can also bind the CDK inhibitor p27Kip1, but with an
      inverse efficiency of their ability to bind to CDK1. Our results identify a new
      family of mammalian proteins that can activate CDKs and therefore potentially
      function as cell cycle regulators. The ability of RINGO proteins to activate CDK1
      and CDK2 suggest also cyclin-independent roles for these kinases.

PMID- 15574122
TI  - Accumulation of partly folded states in the equilibrium unfolding of the
      pneumococcal choline-binding module C-LytA.
AB  - Choline-binding modules are present in some virulence factors and many other
      proteins of Streptococcus pneumoniae (Pneumococcus). The most extensively studied
      choline-binding module is C-LytA, the C-terminal moiety of the pneumococcal cell
      wall amidase LytA. The three-dimensional structure of C-LytA is built up from six
      loop-hairpin structures forming a left-handed beta-solenoid with four choline
      binding sites. The affinity of C-LytA for choline and other structural analogues
      allows its use as an efficient fusion tag for single-step purification of hybrid
      proteins. In the present study, we characterize the folding and stability of C
      LytA by chemical and thermal equilibrium denaturation experiments. Unfolding
      experiments using guanidinium chloride at pH 7.0 and 20 degrees C suggest the
      existence of two partly folded states (I1 and I2) in the following model: N
      (native)-->I1<=>I2. The N-->I1 transition is non-co-operative and irreversible,
      and is significant even in the absence of a denaturant. In contrast, the I1<=>I2
      transition is co-operative and reversible, with an associated freeenergy change
      (DeltaG(0)) of 30.9+/-0.8 kJ x mol(-1). The residual structure in the I2 state is
      unusually stable even in 7.4 M guanidinium chloride. Binding of choline
      stabilizes the structure of the native state, induces its dimerization and
      prevents the accumulation of the I1 species ([N]2<=>[I2]2, DeltaG(0)=50.1+/-0.8
      kJ x mol(-1)). Fluorescence and CD measurements, gel-filtration chromatography
      and limited proteolysis suggest that I1 differs from N in the local unfolding of
      the N-terminal beta-hairpins, and that I2 has a residual structure in the C
      terminal region. Thermal denaturation of C-LytA suggests the accumulation of at
      least the I1 species. These results might pave the way for an effective
      improvement of its biotechnological applications by protein engineering.

PMID- 15574123
TI  - Identification of a unique filamin A binding region within the cytoplasmic domain
      of glycoprotein Ibalpha.
AB  - Binding of the platelet GPIb/V/IX (glycoprotein Ib/V/IX) receptor to von
      Willebrand factor is critical for platelet adhesion and aggregation under
      conditions of rapid blood flow. The adhesive function of GPIbalpha is regulated
      by its anchorage to the membrane skeleton through a specific interaction with
      filamin A. In the present study, we examined the amino acid residues within the
      cytoplasmic tail of GPIbalpha, which are critical for association with filamin A,
      using a series of 25-mer synthetic peptides that mimic the cytoplasmic tail
      sequences of wild-type and mutant forms of GPIbalpha. Peptide binding studies of
      purified human filamin A have demonstrated a major role for the conserved
      hydrophobic stretch L567FLWV571 in mediating this interaction. Progressive
      alanine substitutions of triple, double and single amino acid residues within the
      Pro561-Arg572 region suggested an important role for Trp570 and Phe568 in
      promoting GPIbalpha binding to filamin A. The importance of these two residues in
      promoting filamin A binding to GPIbalpha in vivo was confirmed from the study of
      Chinese-hamster ovary cells expressing GPIbalpha Trp570-->Ala and Phe568-->Ala
      substitutions. Phenotypic analysis of these cell lines in flow-based adhesion
      studies revealed a critical role for these residues in maintaining receptor
      anchorage to the membrane skeleton and in maintaining cell adhesion to a von
      Willebrand factor matrix under high-shear conditions. These studies demonstrate a
      novel filamin A binding motif in the cytoplasmic tail of GPIbalpha, which is
      critically dependent on both Trp570 and Phe568.

PMID- 15574124
TI  - FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation.
AB  - BACKGROUND INFORMATION: FLRG (follistatin-related gene) is a secreted
      glycoprotein that is highly homologous with follistatin. These proteins are
      involved in the regulation of various biological effects mediated by their
      binding to TGF-beta (transforming growth factor-beta) superfamily members,
      activin A and bone morphogenetic proteins. To characterize further the function
      of FLRG, we used a yeast two-hybrid screen to look for other possible functional
      partners. RESULTS: We report a direct interaction between the cysteine-rich
      domain of FLRG and ADAM12 (a disintegrin and metalloprotease 12). ADAMs are
      metalloprotease-disintegrin proteins that have been implicated in cell adhesion,
      protein ectodomain shedding, matrix protein degradation and cell fusion. Several
      studies have reported that ADAM12 protein, as well as activin A, are important
      regulators of osteoclast differentiation. We observed that the expressions of
      ADAM12 and activin A are modulated during osteoclast formation, whereas the FLRG
      expression seemed to remain quite constant. We showed that the FLRG protein
      inhibits osteoclast differentiation from murine primary spleen cells and
      macrophage RAW264.7 cells cultured in the presence of RANK-L (receptor activator
      of nuclear factor kappaB ligand) and M-CSF (macrophage colony-stimulating
      factor). Addition of FLRG protein to precursors significantly reduces the number
      of osteoclasts, as well as the average number of nuclei in each osteoclast.
      CONCLUSIONS: Our study indicates that the FLRG protein may contribute to bone
      formation by inhibiting osteoclast differentiation.

PMID- 15574125
TI  - Re-evaluation of the relationship between migraine and persistent foramen ovale
      and other right-to-left shunts.

PMID- 15574126
TI  - Mannosamine supplementation extends the N-acetylglucosaminylation of recombinant
      human secreted alkaline phosphatase produced in Trichoplusia ni (cabbage looper)
      insect cell cultures.
AB  - A major limitation of the insect cell-baculovirus expression vector system is its
      poor capacity to perform complex glycosylation, since the glycoproteins produced
      are usually only of the high-mannose and paucimannose types. Nonetheless, recent
      evidence indicates that, under various conditions, some insect cell lines are
      capable of producing complex-type glycans. In the present study, we assessed the
      effects of supplementation with ManN (mannosamine) ManNAc (N-acetylmannosamine)
      and Cyt (cytidine) on the glycosylation of recombinant human secreted alkaline
      phosphatase produced by suspension cultures of Trichoplusia ni (cabbage looper)
      BTI-Tn5B1-4 cells. Addition of ManN in the range 5-20 mM resulted in a 10-fold
      increase of the terminal GlcNAc (N-acetylglucosamine) associated with the
      recombinant protein produced after baculovirus infection. Such an increase
      yielded a maximum of 12.5% hybrid glycans having terminal GlcNAc with respect to
      total N-linked glycans. In contrast, no changes in the glycan composition
      associated with recombinant human secreted alkaline phosphatase were observed on
      supplementation with up to 20 mM ManNAc or up to 1.5 mM Cyt. N-acetyl-beta
      glucosaminidase activity in cell extracts was decreased on incubation with 20 mM
      ManN, but not with 20 mM ManNAc or 1.5 mM Cyt, indicating that the increased
      proportion of hybrid glycans obtained on the addition of ManN could be a result
      of N-acetyl-beta-glucosaminidase inhibition.

PMID- 15574127
TI  - Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves
      endothelial function in heart failure.
AB  - ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type
      5) inhibitors have each been reported to improve endothelial function in
      cardiovascular disease patients, but the comparative and combined effects of
      these two classes have not been studied previously. We sought to characterize the
      acute effects of ramipril alone, sildenafil alone, or their combination on
      endothelial function in patients with CHF (chronic heart failure). CHF subjects
      (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of
      sildenafil alone or a combination of ramipril and sildenafil in a double-blind
      manner. FMD (flow-mediated dilation) of the brachial artery was determined by
      high-resolution ultrasound imaging before and at 1, 2 and 4 h after
      administration of the study drug. Ramipril alone increased FMD at 4 h compared
      with placebo (+2.3+/-1.3%, P=0.02). Sildenafil alone increased FMD at 1, 2 and 4
      h compared with placebo (+3.9+/-1.4, +4.6+/-1.8 and +3.7+/-1.3% respectively, all
      P<0.02). Sildenafil in combination with ramipril increased FMD at 1, 2 and 4 h
      when compared with placebo (+3.5+/-1.5, +4.5+/-1.8 and +4.8+/-1.3% respectively,
      all P<0.03). Ramipril and sildenafil both acutely improved FMD in patients with
      CHF, with additive effects evident at 4 h during combination therapy. Therefore
      further work to characterize chronic effects of combined ACE and PDE5 inhibition
      on endothelial function are warranted.

PMID- 15574129
TI  - A novel insertional mutation in Connexin 32 gene causes demyelinating
      polyneuropathy with predominantly motor axonal loss.

PMID- 15574130
TI  - Long-standing idiopathic hypoparathyroidism masking coexistent chronic
      inflammatory demyelinating polyneuropathy.

PMID- 15574131
TI  - Prolonged and excessive phenytoin therapy leading to a severe and partially
      reversible polyneuropathy.

PMID- 15574132
TI  - Close apposition and exposure of non-myelinated axons in traumatic neuromas of
      the human lingual nerve.
AB  - Peripheral nerve injury is sometimes followed by the development of persistent
      painful sensory disorders, such as dysaesthesia. The aetiology of these disorders
      is not clear, but abnormal behaviour of damaged axons at the injury site is
      likely to be involved. In this study, we quantified some ultrastructural
      characteristics that may be related to the development of abnormal spontaneous
      activity, sympathetic interactions, and fibre-to-fibre crosstalk. Using electron
      microscopy, we have determined the frequency and extent of axonal exposure and
      close apposition among non-myelinated axons from 34 traumatic neuromas of the
      human lingual nerve. These specimens were removed at the time of microsurgical
      nerve repair, and the presence or absence of symptoms of dysaesthesia was
      determined pre-operatively. Comparisons were also made with eight normal control
      lingual nerve specimens obtained from patients undergoing organ donor retrieval.
      More non-myelinated axons showed signs of axonal exposure in traumatic neuromas
      (26%) than in controls (5%), and exposure was higher in nerve-end neuromas (31%)
      than in neuromas-in-continuity (22%). In addition, the proportion of the non
      myelinated axolemma that was exposed was significantly higher in neuromas (32%)
      than in controls (21%). The frequency of close apposition between neighbouring
      non-myelinated axons was also higher in neuromas (11%) than in controls (0.35%).
      The majority of axons showing signs of exposure or close apposition had diameters
      <1 microm. These ultrastructural changes may account for some of the altered
      electrophysiological properties of axons within neuromas. However, no significant
      correlations were found between these ultrastructural characteristics and the
      patients' reported symptoms of dysaesthesia.

PMID- 15574133
TI  - Erectile dysfunction as a sentinel symptom of cardiovascular autonomic neuropathy
      in heavy drinkers.
AB  - Because autonomic neuropathy (AN) is not routinely assessed in chronic
      alcoholism, its features and relationship with other disease parameters remain
      undefined. The very existence of true alcohol-related autonomic dysfunction, in
      the absence of alcoholic hepatopathy, is even controversial. We aimed this study
      at evaluating the frequency and pattern of AN in a population of heavy drinkers
      without liver dysfunction. We also investigated the putative risk factors for AN
      as well as its relationship to peripheral neuropathy (PN). Autonomic function was
      evaluated in 70 detoxified alcoholics and 70 well-matched controls by heart-rate
      response to deep breathing, heart-rate response to standing from lying position,
      and blood pressure response to standing up. PN was assessed by electroneurography
      (ENG). Detailed information about sensorimotor and autonomic symptoms,
      nutritional status, and parameters reflecting alcohol intake were recorded. No
      patients showed signs of caloric/protein malnutrition. PN was found in 74% and AN
      (abnormal test results in two of three tests performed) in 26%; abnormalities in
      at least one autonomic test were found in 62%. All patients with PN were
      symptomatic, mainly due to sensory disturbances. In line with this, ENG
      abnormalities were more evident at sural nerves. AN was symptomatic in 10 of 18
      patients, and its sole clinical expression was impotence: indeed, the pattern of
      autonomic involvement was mainly parasympathetic. AN did not correlate with PN,
      nor with any parameter reflecting the amount of alcohol intake; only performances
      on heart-rate response to standing from lying position were related to the
      duration of abuse. The lack of correlation between PN and AN may suggest a
      different pathophysiology for these two complications. Unlike PN, AN is often
      asymptomatic. Among symptomatic patients (55%), erectile dysfunction seems to be
      the sole symptom, in line with the higher degree of parasympathetic damage.

PMID- 15574134
TI  - Plasticity of the different neuropeptide-containing nerve fibres in the tongue of
      the diabetic rat.
AB  - Common oral complications of diabetes mellitus are xerostomia, impairment of
      taste, atrophic lesions of the tongue, leukoplakia, lichen oris planus, and
      tumours, which might be the consequence of chronic inflammation and changes in
      innervation. In this work, we examined the density of different neuropeptide
      containing nerve fibres immunohisto- and immunocytochemically in the root of the
      control and diabetic rat's tongue. Quantitative analysis showed that the number
      of immunoreactive (IR) nerve fibres was decreased after 1 week of the
      streptozotocin treatment, which was prevented by immediate insulin treatment.
      However, after 4 weeks duration of diabetes, the number of all investigated IR
      nerve fibres increased significantly (p<0.05), which was further enhanced by the
      delayed insulin treatment. The numbers of substance P (SP) and vasoactive
      intestinal polypeptide IR perikarya were also increased by insulin treatment. The
      electron-microscopic investigations showed that some of the nerve terminals from
      diabetic animals were found in degeneration. After 4 weeks duration of diabetes,
      the number of inflammatory cells as well as the mast cell/nerve fibre contacts
      was also increased. The immunocells also showed IR for SP and neuropeptide Y in
      the diabetic rats. The insulin treatment decreased both the number and the
      immunoreactivity of these cells. The increased synthesis and/or regeneration of
      neuropeptide-containing nerves might indicate the plasticity of nerve fibres in
      diabetes mellitus, which might happen as a consequence of the changes in the
      level of neurotrophic factors released by increased number of inflammatory cells
      or as an effect of insulin.

PMID- 15574135
TI  - Cutaneous silent period in human immunodeficiency virus-related peripheral
      neuropathy.
AB  - The aim of this work was first to determine whether the cutaneous silent period
      (CSP), a marker of small-nerve-fibre function, was altered in human
      immunodeficiency virus (HIV)-positive subjects with predominantly sensory
      symmetrical polyneuropathy and, second, to assess whether such alterations were
      predictive of an impairment in the largest calibre sensory and motor nerve fibres
      of the upper limb (UL) peripheral nerves. CSP was assessed in three groups of
      subjects: healthy control subjects, HIV-positive subjects with peripheral
      neuropathy (PN) of the lower limbs, and HIV-positive patients with clinical and
      neurophysiological involvement of the four limbs. CSP study showed a significant
      increase of the latency compared to the controls both in HIV-positive cases with
      no impairment in the UL (p=0.006) and in patients with four-limb neuropathy
      (p=0.002). CSP study in HIV-positive patients with mild lower limb distal sensory
      polyneuropathy can detect an early involvement of the UL peripheral nerves. CSP
      latency increase could therefore be addressed as the first sign of PN spreading
      to the UL.

PMID- 15574136
TI  - Amyloid neuropathy: a retrospective study of 35 peripheral nerve biopsies.
AB  - We performed a retrospective study of 35 peripheral nerve biopsies (PNBs) with
      amyloid deposits in the endoneurium. In every case, nerve lesions were studied on
      paraffin-embedded fragments (PEFs) and by ultrastructural examination (USE). In
      addition, muscle fragments were taken and embedded in paraffin.
      Immunohistochemistry was performed with anti-transthyretin (TTR) serum on 19
      nerve and 15 muscle PEFs. Direct immunofluorescence with anti-light-chain sera
      was performed on frozen nerve fragments in 19 cases. Endoneurial amyloid deposits
      were easily identified on routine PEF in 26 cases, after Congo red or thioflavine
      staining in three, and by USE in six. A dramatic myelinated fiber loss was
      evidenced in 34 cases (77-2970 per mm2), and features of axonal degeneration were
      present in every case. Segmental demyelination was observed in 10 cases. A
      mutation in the TTR gene was present in 14 cases, with Met30 mutation in 10 and
      Ala49 in four members of the same family. Amyloid deposits were strongly marked
      by the anti-TTR serum in 11 other cases, twice in the endoneurium, five around
      muscle fibers, and four in both locations. In eight patients, light-chain
      positivity was evidenced in endoneurial deposits, lambda in six and kappa in two.
      Two other patients with monoclonal gammopathy did not present any light-chain
      fixation. In 17 cases, amyloidosis was disclosed by PNB and 13 had a TTR
      pathology; eight of them, over 65 years old, correspond to a late-onset form of
      familial amyloid polyneuropathy which is an underdiagnosed condition.

PMID- 15574137
TI  - Diabetes-induced expression of activating transcription factor 3 in mouse primary
      sensory neurons.
AB  - Diabetic neuropathy (DN) is a complication of diabetes that affects the distal
      terminals of lengthy-projecting sensory axons. To determine whether diabetes
      induced axonal degeneration induces gene expression similar to nerve injury, the
      expression of activating transcription factor 3 (ATF3) by primary sensory neurons
      was examined in an experimental mouse model of DN. Diabetes was induced using
      streptozotocin in C57BL/6 mice, and ATF3 expression in lumbar dorsal root ganglia
      was assessed at different time points and correlated with the markers of
      unmyelinated and myelinated neuronal populations. ATF expression was first
      evident 3 weeks after diabetes induction in both small unmyelinated and large
      myelinated neurons, but it was more prevalent in larger neurons. At 6 weeks, ATF3
      was expressed by neurons among smaller size ranges, but this shift occurred
      principally within myelinated populations. The retrograde labeling of neurons
      innervating the flank and paw skin using Fluoro-Gold labeled appropriate
      percentages of ATF3-positive neurons at 3 weeks, suggesting ATF3 is expressed by
      neurons capable of transporting substances. However, the percentage of double
      labeled neurons was substantially reduced at 6 weeks, suggesting this capacity
      decreases during disease progression. Finally, behavioral responses to noxious
      cutaneous stimuli were assessed. Although no differences to radiant heat were
      observed, diabetic mice developed severe mechanical hypoalgesia 4-5 weeks after
      diabetes induction. These results demonstrate that the diabetes-induced damage of
      sensory axons can induce the expression of genes linked to peripheral nerve
      injury and may identify neurons undergoing nerve damage. Finally, the ability to
      detect sensory deficits in diabetic mice occurs after the expression of injury
      related gene ATF3, suggesting that nerve damage may be underway prior to the
      appearance of behavioral deficits.

PMID- 15574138
TI  - Investigating mechanical behaviour at a core-sheath interface in peripheral
      nerve.
AB  - As peripheral nerves bend and stretch, internal elements need to move in relation
      to each other. However, the way in which intraneural components interact is
      poorly understood. Previous work identified a distinct core and sheath in the rat
      sciatic nerve and provides a useful model with which to investigate this
      interaction. Here we have focused on identifying the mechanical and anatomical
      characteristics of the interface between core and sheath. Nerve samples, 15 and
      20 mm long, of rat sciatic nerves were harvested and placed in a purpose-built
      jig, and a tensile testing machine was used to pull core from sheath. Mechanical
      tests of specimens in which core had been previously pulled from sheath by 25% of
      its initial length achieved a mean pull-out force approximately six times smaller
      than that achieved using intact controls. These results are consistent with the
      proposal that core-sheath interactions involve physical connections rather than a
      viscous fluid interface. Anatomical features of this interface were characterised
      using transmission electron microscopy. It appeared that sheath was derived from
      epineurium and most of the perineurium, whilst core consisted of endoneurium and
      a small proportion of the perineurium: the plane of cleavage appeared to involve
      the innermost perineurial cell layer.

PMID- 15574139
TI  - Effects of 5-HT2A receptor antagonist on blood flow in chronically compressed
      nerve roots.
AB  - Neurogenic intermittent claudication (NIC) can be caused by compression of the
      cauda equina by spinal stenosis and is a major clinical problem. A reduction of
      blood flow is an important mechanism for inducing NIC and may be caused by a
      vasoconstrictive effect mediated by the serotonin 5-HT2A receptor in chronic
      cauda equina compression lesions. This study assessed the effects of the 5-HT2A
      receptor antagonist on nerve vasculature in chronically compressed nerve roots. A
      plastic balloon was placed under the lamina of L7 and inflated to 10 mmHg and
      left for 1 week in several cauda equina compression models. All experimental
      animals received an acute administration of serotonin. One group received
      sarpogrelate hydrochloride (5-HT2A receptor antagonist: 5-HTRA) before
      administration of serotonin, and another group was administered 5-HTRA after
      administration of serotonin. Diameters and blood flow in the vasculature of S2 or
      S3 nerve roots were measured after injection of serotonin. In animals without
      compression of the cauda equina (sham), blood vessels contracted and the blood
      flow was reduced after administration of serotonin. In sham and compression
      animals receiving both serotonin and 5-HTRA, blood vessel diameter was not
      reduced and was significantly larger than that in the compression group receiving
      only serotonin (p<0.05). Likewise, the blood flow was not reduced in sham and
      compression animals receiving serotonin and 5-HTRA and was significantly greater
      in the compression group treated only with serotonin. 5-HTRA inhibited
      vasoconstriction and the reduction of blood flow in chronically compressed nerve
      roots challenged with serotonin. This fact suggests that 5-HTRA might be
      effective at improving blood flow in chronically compressed nerve roots in
      patients with spinal canal stenosis and changes in circulation levels of
      serotonin.

PMID- 15574140
TI  - Adhesives and adhesions: intestinal surgery on a sticky wicket!

PMID- 15574141
TI  - Minimally invasive radical prostatectomy: now safe and efficacious.

PMID- 15574142
TI  - Outcome of endoleak following endoluminal abdominal aortic aneurysm repair.
AB  - BACKGROUND: The most important complication of endoluminal abdominal aortic
      aneurysm repair is endoleak, in which there is persistent blood flow outside the
      graft but within the aneurysm sac. Depending on endoleak type, there is an
      ongoing potential for aneurysm expansion or rupture. Conversely, some endoleaks
      may resolve spontaneously. Absolute indications for interventional management of
      endoleaks remain elusive due to the heterogeneous nature of leaks and uncertainty
      in predicting their outcome. METHODS: A retrospective review was conducted on all
      endoluminal graft recipients with endoleaks at Repatriation General Hospital over
      a 3-year period. Data were collected via a database maintained by the Department
      of Vascular Surgery, and hospital casenotes. RESULTS: Sixty-six patients
      underwent endoluminal graft insertion in the study period. Fourteen endoleaks
      were observed in 11 patients, representing an endoleak rate of 21.2%. There were
      three type I leaks and 11 type II leaks. One type I leak resolved spontaneously,
      one resolved immediately following interventional management, and one resolved 6
      months after interventional management. Interventional treatment was undertaken
      in seven cases of type II leak due to increase in aneurysm diameter by 5 mm. Two
      type II endoleaks resolved spontaneously. Aneurysm diameter increased in two
      patients following radiographic resolution of their endoleaks. There were no
      cases of aneurysm rupture. CONCLUSIONS: Initial observation is a reasonable
      management option in most cases of type II endoleak, because some will
      spontaneously resolve during follow up. Those associated with increase in
      aneurysm size should undergo interventional treatment. Conservative management of
      type I endoleaks may be undertaken in extreme isolated cases.

PMID- 15574144
TI  - Prospective trial of intraoperative radiation treatment for breast cancer.
AB  - BACKGROUND: A new device, Intrabeam, is available for intraoperative
      radiotherapy. We have prospectively examined its feasibility and tolerability in
      delivering adjuvant breast cancer treatment. METHODS: Thirty-five patients
      undergoing breast-conserving surgery received targeted tumour bed irradiation
      consisting of 5 Gy (at 10 mm) in a single fraction. This single intraoperative
      treatment was used to replace the external beam radiotherapy "boost" that would
      usually be given in 10 daily treatments following 5 weeks of whole breast
      irradiation. Patients later completed external beam radiotherapy as usual.
      Potential toxicities were prospectively assessed fortnightly prior to external
      beam radiotherapy, weekly during it, and 3 monthly subsequently. RESULTS: The
      intraoperative radiotherapy was able to be delivered without difficulty, either
      at time of initial cancer surgery or as a second procedure. When performed as a
      separate procedure the median operating time was 56 min. The treatment was well
      tolerated, with only one patient experiencing any grade 3 or 4 toxicities--this
      was acute grade three itch. There was an overall early breast infection rate of
      17%. No unexpected toxicities were seen. CONCLUSIONS: This simple and well
      tolerated treatment delivers a useful radiation dose to the area of highest risk
      of tumour recurrence. The early infection rate is similar to that reported in the
      literature, for treatments without intraoperative radiotherapy. Whether such a
      treatment may adequately replace the entire adjuvant radiation therapy treatment
      for low-risk patients is now being studied in a randomized trial.

PMID- 15574145
TI  - Oral iron therapy for anaemia after orthopaedic surgery: randomized clinical
      trial.
AB  - BACKGROUND: Oral iron therapy is often used after orthopaedic surgery to improve
      haemoglobin levels. The aim of the present trial was to determine if
      administration of oral iron after orthopaedic surgery results in a better
      improvement of haemoglobin levels than a control treatment. METHODS: This was a
      double blind randomized controlled trial at a tertiary referral orthopaedic
      centre. The participants were patients undergoing elective hip or knee
      replacement surgery with normal iron and folic acid stores and no history of iron
      deficiency, and the primary outcome was the haemoglobin level 10 weeks after
      surgery. RESULTS: At 10 weeks the mean +/- SD haemoglobin in the iron group was
      132.8 +/- 13.4 g/L and in the control group it was 128.0 +/- 10.6 g/L, a
      difference of 4.8 g/L with a 95% confidence interval for the difference of -1.2
      to 10.7 g/l, P = 0.12. CONCLUSIONS: Iron taken after elective hip or knee
      replacement surgery does not result in higher haemoglobin 10 weeks after surgery,
      or a faster rate of increase in haemoglobin than a control treatment.

PMID- 15574146
TI  - Role of intraoperative frozen section in the management of thyroid nodules.
AB  - BACKGROUND: The role of intraoperative frozen section in the management of
      thyroid nodules is controversial. Its potential benefit is to facilitate one
      stage total thyroidectomy. Most literature on this topic originates from overseas
      tertiary referral centres with a high percentage of cancer cases and a fully
      resourced frozen section service. The aim of the present study was to review all
      patients undergoing frozen section at a typical general surgical department in
      New Zealand (North Shore Hospital, Auckland) to see how often frozen section
      altered surgical strategy. METHODS: A retrospective review of all frozen sections
      between November 1999 and June 2003 was performed. Patient records, operation
      notes and pathology reports were reviewed. RESULTS: Forty-seven sequential frozen
      sections were included in the study. Thirteen patients had thyroid carcinoma
      (five follicular, three Hurthle cell, and five papillary). In only one patient
      did the result of an intraoperative frozen section result in a total
      thyroidectomy being performed instead of a thyroid lobectomy. The reason for this
      was the rare condition of Riedel's thyroiditis. In no patients did frozen section
      detect a cancer that was not diagnosed on preoperative fine-needle aspirate
      biopsy. CONCLUSION: The present review found little benefit in performing
      intraoperative frozen section in this setting. As a diagnostic test the cost of
      frozen section (NZ $200 for each frozen section) needs to be weighed against its
      low clinical benefit.

PMID- 15574147
TI  - Laparoscopy in the management of colorectal cancer metastatic to the liver.
AB  - BACKGROUND: This investigation was undertaken to define the value of laparoscopy
      in the staging of patients with colorectal carcinoma metastatic to the liver.
      METHODS: The clinical details of 59 consecutive patients with colorectal liver
      metastases undergoing laparoscopy prior to planned hepatectomy were entered
      prospectively on a computerized database. All patients were staged preoperatively
      with thin slice (5-7 mm) helical computed tomography chest, abdomen and pelvis.
      Synchronous metastases were defined as those found during, or on imaging carried
      out within 1 month of, colorectal resection. Criteria for laparoscopic
      unresectability were: (i) histologically proven extrahepatic disease; (ii)
      bilateral inflow or outflow involvement; (iii) the presence of cirrhosis in
      patients requiring an extended resection (lobectomy or greater); or (iv) hepatic
      metastases involving more than six hepatic segments. RESULTS: In 24 patients with
      synchronous metastases (median age 65 years, range 32-81 years) all were
      resectable on laparoscopic criteria, of whom 21 were resected. Extrahepatic
      disease was found at laparotomy in three patients. In 35 patients with
      metachronous metastases (median age 64 years, range 32-81 years) laparoscopy
      could not be performed in five patients because of adhesions, and three patients
      were deemed unresectable on laparoscopic criteria. Of the remaining 27 patients,
      25 underwent resection while two proved unresectable. Overall eight of 54
      evaluable patients had unresectable disease and laparoscopy correctly identified
      three patients. CONCLUSIONS: Following computed tomography scan, 15% of patients
      with metastatic colorectal carcinoma will be found to have unresectable disease.
      Laparoscopy will identify approximately half. Laparoscopy is of no greater value
      in staging synchronous versus metachronous metastases.

PMID- 15574148
TI  - Clinicopathological characteristics of signet ring cell carcinoma of the stomach.
AB  - BACKGROUND: Signet ring cell (SRC) carcinoma of the stomach is characterized by
      its poor prognosis and potential to infiltrate the wall of stomach, although
      survival studies comparing carcinomas with and without SRC features have yielded
      inconsistent results. This study compared the clinicopathological features and
      prognosis of patients with SRC carcinoma with those with non-signet ring cell
      carcinoma of the stomach (NSRC). METHODS: We reviewed the records of 2358
      patients diagnosed with gastric carcinoma who were treated surgically between
      January 1980 and December 1999 at the Department of Surgery, Chonnam National
      University Hospital. There were 204 patients (8.7%) with SRC carcinoma as
      compared to 2154 with NSRC. RESULTS: Significant differences were noted in the
      mean patient age, mean tumour size, depth of invasion, prevalence of hepatic and
      regional lymph node metastases, tumour stage, and curability between the patients
      with SRC histology and NSRC. There were no statistically significant differences
      in patient gender, location, or peritoneal dissemination between patients with
      SRC carcinoma and NSRC. SRC carcinoma of the stomach had a higher prevalence of
      early gastric carcinoma (46.1%) than NSRC (21.7%). The overall 5-year survival of
      all the patients with SRC carcinoma was 60.2% as compared with 48.9% for the
      patients with NSRC (P < 0.01). Using Cox proportional hazards model, lymph node
      metastasis and curability were significant factors affecting the outcome. Signet
      ring cell histology itself was not an independent prognostic factor. CONCLUSIONS:
      Patients with SRC histology do not have a worse prognosis than patients with
      other types of gastric carcinoma.

PMID- 15574150
TI  - Laparoscopic radical prostatectomy: early safety and efficacy.
AB  - BACKGROUND: To evaluate the initial results of laparoscopic radical prostatectomy
      at this institution. METHODS: Between January 2000 and September 2003, 30
      patients underwent laparoscopic radical prostatectomy. Peri- and postoperative
      data were accumulated prospectively and maintained in a database. All patients
      have a minimum of 6 month follow up. RESULTS: There were no conversions to open
      surgery, and there were no re-operations. Mean operating time was 328 (195-490)
      min. There was one intraoperative rectal injury which was repaired
      laparoscopically. Three patients (10%) required blood transfusion.
      Postoperatively, there were two cases of respiratory depression, one case of
      haemoptysis and one upper gastrointestinal bleed. Two anastomotic leaks were
      successfully treated conservatively, one of which was the only readmission to
      hospital. There was one case of clot retention requiring manual irrigation of the
      bladder. Mean hospital stay was 2.75 (1-10) days, with six of the last 10
      patients being discharged on the first postoperative day. Continence rates at 6
      months are 83%. Positive surgical margins occurred in seven patients (23%). At 12
      months of follow up, one patient (4.5%) has had biochemical recurrence.
      CONCLUSIONS: Our initial results are comparable to, or better than, the initial
      series in high volume centres. The procedure is feasible in appropriately
      selected cases in the Australasian environment.

PMID- 15574151
TI  - Is screening for abdominal aortic aneurysm bad for your health and well-being?
AB  - BACKGROUND: The purpose of the present paper was to investigate whether screening
      for abdominal aortic aneurysm (AAA) causes health-related quality of life to
      change in men or their partners. METHODS: A cross-sectional case-control
      comparison was undertaken of men aged 65-83 years living in Perth, Western
      Australia, using questionnaires incorporating three validated instruments
      (Medical Outcomes Study Short Form-36, EuroQol EQ-5D and Hospital Anxiety and
      Depression Scale) as well as several independent questions about quality of life.
      The 2009 men who attended for ultrasound scans of the abdominal aorta completed a
      short prescreening questionnaire about their perception of their general health.
      Four hundred and ninety-eight men (157 with an AAA and 341 with a normal aorta)
      were sent two questionnaires for completion 12 months after screening, one for
      themselves and one for their partner, each being about the quality of life of the
      respondent. RESULTS: Men with an AAA were more limited in performing physical
      activities than those with a normal aorta (t-test of means P = 0.04). After
      screening, men with an AAA were significantly less likely to have current pain or
      discomfort than those with a normal aorta (multivariate odds ratio: 0.5; 95%
      confidence interval (CI): 0.3-0.9) and reported fewer visits to their doctor. The
      mean level of self-perceived general health increased for all men from before to
      after screening (from 63.4 to 65.4). CONCLUSIONS: Apart from physical
      functioning, screening was not associated with decreases in health and well
      being. A high proportion of men rated their health over the year after screening
      as being either the same or improved, regardless of whether or not they were
      found to have an AAA.

PMID- 15574152
TI  - Surgical management of lung cancer in Western Australia in 1996 and its outcomes.
AB  - BACKGROUND: All cases of lung cancer diagnosed in Western Australia in 1996 in
      which surgery was the primary treatment, were reviewed. Reported herein are the
      characteristics of the patients, the treatment outcomes and a comparison of the
      management undertaken with that recommended by international guidelines. METHODS:
      All patients with a new diagnosis of lung cancer in Western Australia in the
      calendar year of 1996 were identified using two different population-based
      registration systems: the Western Australian (WA) Cancer Registry and the WA
      Hospital Morbidity Data System. A structured questionnaire on the diagnosis and
      management was completed for each case. Date of death was determined through the
      WA Cancer Registry. RESULTS: Six hundred and sixty-eight patients with lung
      cancer were identified; 132 (20%) were treated with surgery. Lobectomy was the
      most frequently performed procedure (71%), followed by pneumonectomy (19%). Major
      complications affected 23% of patients. Postoperative mortality was 6% (3%
      lobectomy, 12% pneumonectomy). At 5 years the absolute survival was as follows
      for stage I, II, IIIA, IIIB, respectively: 51%, 45%, 12%, 5%. CONCLUSIONS:
      Investigations and choice of surgery in WA in 1996 reflect current international
      guidelines. The survival of patients with resectable lung cancer remains
      unsatisfactory.

PMID- 15574153
TI  - Evidence-based risk factors for postoperative deep vein thrombosis.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a common postoperative complication
      that is associated with significant morbidity and mortality. Thromboprophylaxis
      has been shown to be underused. In the absence of prophylaxis, rates as high as
      50% have been reported following orthopaedic surgery, and 25% following general
      surgery. Many risk factors have been suggested but there is often little evidence
      to support these claims. METHODS: A systematic review was performed to determine
      the evidence base behind each suggested risk factor, and, where sufficient data
      were available, a random-effects meta-analysis was performed. RESULTS: There is
      evidence to support a significant association between increased age, obesity, a
      past history of thromboembolism, varicose veins, the oral contraceptive pill,
      malignancy, Factor V Leiden gene mutation, general anaesthesia and orthopaedic
      surgery, with higher rates of postoperative DVT, although there remain some
      variables within the study designs that may lead to overestimation of effect.
      There is no evidence to support the suggested risk factors of hormone replacement
      therapy, gender, ethnicity or race, chemotherapy, other thrombophilias,
      cardiovascular factors, smoking and blood type. CONCLUSIONS: An accurate
      knowledge of evidence-based risk factors is important in predicting and
      preventing postoperative DVT, and can be incorporated into a decision support
      system for appropriate thromboprophylaxis use.

PMID- 15574154
TI  - Sacral nerve stimulation: an emerging treatment for faecal incontinence.
AB  - Faecal incontinence is common, distressing to the patient and socially
      incapacitating. The treatment options depend on the severity and aetiology of
      incontinence. For mild cases of faecal incontinence, medical management and
      pelvic floor physiotherapy may be adequate. For more severe cases, surgery is
      often required. Patients who have a distinct sphincter defect are amenable to
      surgical repair. In many cases, there is a combination of diffuse structural
      damage of the anal sphincters with pudendal neuropathy. Conventional surgical
      repairs have a modest degree of success and the results tend to deteriorate with
      time. Neosphincter procedures such as artificial bowel sphincter and dynamic
      graciloplasty are potentially morbid and technically complex. Sacral nerve
      stimulation is innovative and has had a medium-term success with improvement of
      quality of life in over 80% of patients treated for faecal incontinence. These
      results are superior to other techniques in treating patients with severe
      refractory faecal incontinence, where current maximal therapy has failed. The
      technique is unique because there is a screening phase, which has a high
      predictive value. It is also associated with minimal complications that are
      usually minor. However, most published reports of sacral nerve stimulation for
      treatment of faecal incontinence were case studies and methods of assessing
      outcome were variable. Criteria for patient selection are evolving and are yet to
      be defined. The present paper critically reviews the publications to date on
      sacral nerve stimulation for treatment of faecal incontinence. This will form the
      basis for future evaluation of this emerging treatment of severe, intractable
      faecal incontinence. Randomized clinical trials like that of the Melbourne trial
      will further clarify the role and indications of sacral nerve stimulation for
      faecal incontinence.

PMID- 15574155
TI  - Histoacryl blue versus sutured left colonic anastomosis: experimental study.
AB  - BACKGROUND: Cyanoacrylates have been advocated as a protective seal in colonic
      anastomosis to prevent leakage. In order to assess the effects of n-butyl-2
      cyanoacrylate on left colonic anastomosis it was compared to the sutured
      anastomosis in the rat. METHODS: Forty male Wistar albino rats were divided into
      two groups of 20 each. On days 3 and 7, 10 animals in each group were killed. The
      comparisons between n-butyl-2-cyanoacrylate and sutured groups were made with
      respect to outcome measures including anastomotic leakage, anastomotic stricture,
      peritonitis and wound infections, and adhesion formation, anastomotic bursting
      pressure, histological appearance of the anastomotic area. RESULTS: Although the
      adhesion formation was significantly more extensive in the n-butyl-2
      cyanoacrylate group on day 3 (P < 0.001), there was no significant difference
      between the groups on day 7. The more inflammatory reaction also occurred in the
      n-butyl-2-cyanoacrylate group. The mean +/- SD anastomotic bursting pressure was
      significantly higher in the suture group than in the n-butyl-2-cyanoacrylate
      group (63 +/- 14 mmHg vs 43 +/- 8 mmHg) on day 3. The bursting pressure was also
      found to be higher on day 7 in the suture group (187 +/- 26 mmHg vs 49 +/- 12
      mmHg, P < 0.0001). The suture group had a significantly higher bursting pressure
      on day 7 compared to day 3 (P < 0.05). CONCLUSIONS: Left colonic anastomosis with
      n-butyl-2-cyanoacrylate in rats does not improve the healing process; on the
      contrary, it has a negative influence during the first week. As a consequence,
      the routine use of n-butyl-2-cyanoacrylate in colonic anastomosis in the clinical
      situation does not appear to be justifiable.

PMID- 15574156
TI  - Prevention of adhesions by sodium chromoglycate, dexamethasone, saline and
      aprotinin after pelvic surgery.
AB  - BACKGROUND: The purpose of the present paper was to assess the efficacy of
      saline, sodium chromoglycate, dexamethasone and aprotinin, in single or in
      combined use in reducing postoperative pelvic adhesion formation in a rabbit
      model. METHODS: A standard lesion was performed to induce adhesion formation.
      Forty-five rabbits were divided into nine study groups. Group 1 was the non
      treatment group. In group 2, 3 cm(3) of the rabbits' own serum was instilled i.p.
      In group 3, 5 mg/kg sodium chromoglycate and 3 cm(3) of the rabbits' own serum
      were administered i.p. The group 4 rabbits were instilled with 5 mg/kg sodium
      chromoglycate, 3 cm(3) rabbits' own serum and 1 mg/kg dexamethasone i.p. The
      group 5 rabbits were injected with 5000 units aprotinin i.m. 2 h before operation
      and 5 mg/kg sodium chromoglycate, 3 cm(3) of rabbit serum, 1 mg dexamethasone and
      5000 units aprotinin instilled i.p. In group 6, 3 cm(3) saline was instilled i.p.
      Groups 7, 8 and 9 were a repeat of groups 4, 5 and 6 with the exception of
      replacement of the rabbit serum by 3 cm(3) saline. Animals were evaluated for
      adhesions 10 days after operation. RESULTS: Macroscopic adhesion scores of all
      the groups (2-9) were significantly less than scores of the control group (group
      1). The macroscopic adhesion scores of group 9 and group 8 were significantly
      less compared to that of group 7. CONCLUSION: Intraperitoneal instillation of
      saline and sodium chromoglycate decreased pelvic adhesion formation significantly
      in a rabbit model. Addition of aprotinin and dexamethasone to these agents gave a
      further advantage in decreasing pelvic adhesion formation.

PMID- 15574157
TI  - Teaching subfascial perforator veins surgery: survey on a 2-day hands-on course.
AB  - BACKGROUND: The present paper describes a training method with objective
      evaluation to enhance video-assisted surgical skills in subfascial endoscopic
      perforator veins surgery (SEPS). Training was scheduled during a 2-day intensive
      course. METHODS: Hands-on exercises were performed (i) on a simulator to assess
      whether specific training exercises were helpful in attainment of skills; (ii) on
      a known animal model that uses the swine abdominal wall and which allows practice
      in endoscopic dissection and perforator veins (PV) using appropriate
      instrumentation in an environment that is a reasonable surrogate for the human
      calf; and (iii) assisting a senior surgeon performing SEPS. Thirty surgeons
      without experience in SEPS were trained to perform a sequence of standardized
      drills connected with the SEPS technique. The SEPS simulator consisted of an
      artificially constructed subfascial space of the leg in which false perforator
      veins had to be localized, and cut. The participants performed a sequence of
      drills three times in order to improve their dexterity. The same exercises were
      then performed on a swine model. The model consisted of the arteries and veins
      penetrating the rectus fascia and passing into the overlying cutaneous trunci
      muscle and hypodermis on either side of the midline between the arch of the ribs
      cranially and the umbilicus caudally. Trainees were required to achieve operative
      space in the animal subcutaneous fat, to reach and identify the "perforating"
      subcutaneous vessels, and to interrupt some of them with a 5-mm clamp coagulator
      ultrasonic scalpel. The time required to perform each dexterity drill was
      recorded in seconds. Finally, the day after, trainees were asked to drive the
      senior operator during clinical SEPS performed on eight patients, suggesting the
      following manoeuvres in order to: (i) enter the subfascial space of the leg; (ii)
      make operative space; (iii) identify the incompetent perforator vein(s); and (iv)
      coagulate and divide them with the ultrasonic scalpel. Each of these four steps
      scored 1 point. RESULTS: All the trainees showed a steady improvement in skill
      acquisition on the SEPS simulator (P < 0.001), and on the animal model with the
      single-port technique (P < 0.001). These results reflect positively on the animal
      model using the dual-port technique, and on the scores achieved in the operating
      theatre during clinical SEPS. CONCLUSIONS: The validity of the 2-day course was
      demonstrated by significant improvement in performance with increasing skill on
      the training models, and in clinical practice.

PMID- 15574158
TI  - Africa--surgery in an unstable environment.

PMID- 15574159
TI  - Re: Evidence supports adjuvant radiotherapy in selected patients with rectal
      cancer.

PMID- 15574160
TI  - Improving standards, improving surgery.

PMID- 15574161
TI  - Unlikely cause for a painful hip in a 14-year-old boy.

PMID- 15574162
TI  - Direct percutaneous ethanol sclerotherapy for treatment of a recurrent venous
      malformation in the periorbital region.

PMID- 15574163
TI  - Hen's teeth?: Extranodal marginal zone B cell lymphoma of MALT type in nasal
      mucosa.

PMID- 15574164
TI  - Chronic non-healing anal ulceration and Nicorandil: further evidence of an
      emerging problem.

PMID- 15574165
TI  - Polyorchidism: a case report and review of the literature.
AB  - Polyorchidism is defined as the presence of two or more testes. It is a rare
      anomaly with approximately 77 cases reported in the literature. Polyorchidism is
      frequently associated with additional urological pathologies such as undescended
      testis, inguinal hernia, testicular torsion, hydrocoele, malignancy and
      infertility. Differential diagnosis includes spermatocoele, hydrocoele,
      epididymal cysts or aberrant epididymis. We report on an interesting case of
      polyorchidism in a 15-year-old man diagnosed on ultrasound and we review the
      literature and current management of polyorchidism.

PMID- 15574166
TI  - Methylene blue injection to localize the site of small intestinal haemorrhage.

PMID- 15574167
TI  - Metastatic myoepithelioma of the breast.
AB  - Myoepitheliomas are typically benign tumours arising from exocrine glands. There
      have only been five reports of malignant myoepitheliomas from breast origin
      previously published in the English literature. This report describes a patient
      with myoepithelioma arising in the breast which later metastasized despite the
      primary tumour having benign histological features. Impaired immune function due
      to end-stage renal failure and haemodialysis may have contributed to the
      malignant potential of her tumour. The literature regarding myoepithelial tumours
      is reviewed. All breast myoepitheliomas should be managed as potentially
      malignant tumours with appropriate surgical clearance and staging.

PMID- 15574168
TI  - Surgery for left-sided carcinoid heart disease.

PMID- 15574169
TI  - Mechanism of repolarization change during initiation of supraventricular
      tachycardia.
AB  - INTRODUCTION: Previous literature has documented the association between narrow
      QRS supraventricular tachycardia (SVT) and pronounced ST-T segment change. The
      aim of this study was to evaluate repolarization changes during SVT initiation
      and demonstrate the possible mechanism. METHODS AND RESULTS: Fifty-one
      consecutive patients (20 men and 31 women; mean age 46.1 +/- 16.4 years) with
      narrow QRS SVT (32 patients with AV nodal reentrant tachycardia and 19 patients
      with AV reentrant tachycardia) were included. We retrospectively analyzed the
      intracardiac recordings and ST-T segment changes on 12-lead surface ECGs during
      SVT initiation. Twenty-six (51%) patients developed ST segment repolarization
      changes during SVT initiation. Patients with shorter baseline sinus cycle length,
      shorter tachycardia cycle length, elevated systolic blood pressure before
      tachycardia induction, and greater reduction of systolic blood pressure had a
      higher incidence of repolarization changes. However, multivariate analysis showed
      that reduction of systolic blood pressure after SVT induction was the only
      independent predictor of repolarization changes. Furthermore, the maximal degree
      of ST segment depression during SVT correlated with the reduction of systolic
      blood pressure (r = 0.75, P < 0.001). CONCLUSION: Repolarization changes during
      SVT initiation were caused mainly by concurrent hemodynamic change after SVT
      initiation with abrupt cycle length shortening.

PMID- 15574170
TI  - Improved localization of right-sided accessory pathways with microcatheter
      assisted right coronary artery mapping in children.
AB  - INTRODUCTION: Radiofrequency ablation of some right-sided accessory pathways
      continues to be challenging. The purpose of this study was to evaluate the
      efficacy of introducing a multielectrode microcatheter in the right coronary
      artery to localize accessory pathways when conventional mapping was unsuccessful.
      METHODS AND RESULTS: A retrospective study was conducted of all right-sided
      accessory pathway radiofrequency ablation procedures in which a multielectrode
      microcatheter as a reference in the right coronary artery was used to assist
      mapping. Between January 1998 and January 2002, 10 patients (5 males) underwent
      mapping of 11 accessory pathways with this technique at mean age of 12.3 +/- 3.8
      years. Five patients had Ebstein's anomaly of the tricuspid valve. Accessory
      pathways were identified in the following locations: right anterior 3, right
      anterolateral 2, right lateral 1, right posterolateral 2, and right posterior 3.
      Mean procedure time was 285 +/- 70.3 minutes, and fluoroscopy time was 68.7 +/-
      21 minutes. Average mapping duration prior to microcatheter insertion in the
      right coronary artery was 136 +/- 40 minutes. After microcatheter placement in
      the right coronary artery, the time to successful ablation of accessory pathways
      was 38 +/- 11 minutes. All 11 (100%) accessory pathways were successfully
      ablated. CONCLUSION: Mapping in the right coronary artery with a microcatheter is
      an effective method to improve localization and successful ablation of difficult
      right-sided accessory pathways.

PMID- 15574171
TI  - Multielectrode coronary artery catheterization: still an effective tool in
      ablation of right free-wall accessory pathways.

PMID- 15574172
TI  - Stable secondary arrhythmias late after intraoperative radiofrequency ablation of
      atrial fibrillation: incidence, mechanism, and treatment.
AB  - INTRODUCTION: Intraoperative radiofrequency (RF) ablation is an effective
      treatment of atrial fibrillation (AF). However, secondary arrhythmias late after
      ablation may complicate the patient's course. We report on the incidence,
      mechanisms, and treatment of gap-related atrial flutter and other secondary
      arrhythmias during long-term follow-up. METHODS AND RESULTS: In 129 patients who
      underwent intraoperative RF ablation with placement of left atrial linear lesions
      using minimally invasive surgical techniques, secondary arrhythmias were analyzed
      during long-term follow-up (20 +/- 6 months). Transient atrial arrhythmias during
      the first 3 postoperative months were excluded. In 8 (6.2%) of 129 patients,
      sustained stable secondary arrhythmias were documented. Left atrial, gap-related
      atrial flutter was observed in 4 patients (3.1%). The flutter was treated by
      percutaneous RF ablation in 3 patients (2.3%) and with drugs in 1 patient (0.8%).
      In 2 patients (1.6%), right atrial isthmus-dependent atrial flutter occurred and
      was treated successfully by percutaneous RF ablation. In 2 patients (1.6%),
      ectopic right atrial tachycardias occurred and were treated with percutaneous RF
      ablation. CONCLUSION: Late after intraoperative RF ablation of atrial
      fibrillation, three types of stable secondary arrhythmias were observed in 6% of
      patients: left atrial gap-related atrial flutter, right atrial isthmus-dependent
      atrial flutter, and ectopic atrial tachycardia. Gaps after intraoperative RF
      ablation due to noncontinuous or nontransmural linear lesions may lead to stable
      left atrial macroreentrant tachycardias, requiring new interventional therapy.

PMID- 15574173
TI  - Clinical assessment of antiarrhythmic agents for paroxysmal atrial fibrillation
      guided by modification of electrophysiologic arrhythmogenicity.
AB  - INTRODUCTION: Rapid atrial pacing alters atrial electrophysiology, promoting
      initiation and maintenance of atrial fibrillation (AF). The aim of this study was
      to assess differences in the electrophysiologic properties of atrial tissue
      between patients with and without AF episodes and to determine whether
      electrophysiologic properties can predict the clinical efficacy of antiarrhythmic
      agents. METHODS AND RESULTS: Sixty patients were studied, 33 with documented
      episodes of paroxysmal atrial fibrillation (PAF) and 27 control patients. Atrial
      effective refractory period (AERP), atrial vulnerability, and intra-atrial
      conduction time were measured at baseline and after rapid constant atrial pacing
      for 5 minutes at rates of 130, 150, 170, and 190 beats/min. The clinical efficacy
      of antiarrhythmic agents for PAF prophylaxis was assessed over 14 months with an
      antiarrhythmic agent identical to that administered intravenously, and the
      antiarrhythmic agent effects on AERP, atrial vulnerability, and intra-atrial
      conduction time were assessed. AERP shortening and atrial vulnerability increase
      were significantly larger in the PAF group. Antiarrhythmic agents that were
      clinically effective in suppressing PAF significantly attenuated AERP shortening,
      but antiarrhythmic agents that were clinically ineffective did not. CONCLUSION:
      Changes in AERP and atrial vulnerability observed after rapid atrial pacing are
      considered indicative of the electrophysiologic substrate of PAF. Attenuation of
      AERP and atrial vulnerability by antiarrhythmic agents might be useful in
      predicting their clinical efficacy.

PMID- 15574174
TI  - Incidence and risk factors of early venous thrombosis associated with permanent
      pacemaker leads.
AB  - INTRODUCTION: Pacemaker lead implantation can cause thrombosis, which can be
      associated with serious local morbidity and complicated by pulmonary embolism.
      Few reliable estimates of the incidence of thrombosis have been reported. The
      contribution of established risk factors to venous thrombosis in patients with
      implanted pacemaker leads is unknown. METHODS AND RESULTS: One hundred forty-five
      consecutive patients n = 145) underwent routine clinical and Doppler ultrasound
      evaluation for thrombosis before and 3, 6, and 12 months after lead implantation.
      Established risk factors for venous thrombosis were assessed in detail for all
      patients. Clinical outcome, including clinically manifest thrombosis, pulmonary
      embolism, associated pacemaker lead infection, complicated reinterventions, and
      death, was evaluated. Thrombosis was observed in 34 (23%) of 145 patients.
      Thrombosis did not cause any signs or symptoms in 31 patients but resulted in
      overt clinical symptoms in 3 patients. The absence of anticoagulant therapy, use
      of hormone therapy, and a personal history of venous thrombosis were associated
      with an increased risk of thrombosis. The risk of thrombosis increased in the
      presence of multiple pacemaker leads compared to a single lead. CONCLUSION:
      Established risk factors for venous thrombosis and the presence of multiple
      pacemaker leads contribute substantially to the occurrence of thrombosis
      associated with permanent pacemaker leads. Risk factor assessment prior to
      implantation may be useful for identifying patients at risk for thrombotic
      complications. Preventive management in these patients is warranted.

PMID- 15574175
TI  - Lead-induced venous thrombosis:consequences?

PMID- 15574176
TI  - Prevalence, predictors, and mortality significance of the causative arrhythmia in
      patients with electrical storm.
AB  - INTRODUCTION: Electrical storm (ES) is characterized by either refractory
      ventricular tachycardia (VT) or ventricular fibrillation (VF). However, little is
      known about the prevalence, predictors, and mortality implications of the
      causative arrhythmia in ES. We sought to assess the prevalence, predictors, and
      survival significance of VT and VF as the causative arrhythmia of ES in
      implantable cardioverter defibrillator (ICD) patients. METHODS AND RESULTS:
      Consecutive patients from January 2000 to December 2002 who presented to the ICD
      clinic with > or = 2 separate ventricular arrhythmic episodes requiring shock
      within 24 hours were included in the study. ICD interrogation confirmed the
      number of shocks and provided electrograms for interpretation of the causative
      arrhythmia. Patients were grouped as VF or VT according to the causative
      arrhythmia. Their prevalence, predictors, and mortality rates were compared. Of
      2,028 patients assessed in the ICD clinic, 208 (10%) presented with ES. VF was
      the cause of ES in 99 of 208 patients, for an overall prevalence of 48%. Original
      ICD indication, coronary artery disease, and amiodarone therapy were predictive
      for the causative arrhythmia. There was no mortality difference between the VT
      and VF groups; however, both groups had significantly increased mortality
      compared to a control ICD population without ES. CONCLUSION: VF is the causative
      arrhythmia for a sizable proportion of patients with ES. The initial ICD
      indication, coronary artery disease, and amiodarone therapy are predictors of the
      causative arrhythmias in ES. There does not appear to be any mortality difference
      between ES patients with VT and VF, but mortality is increased in patients with
      ES versus control ICD patients without ES.

PMID- 15574177
TI  - Fever as a precipitant of idiopathic ventricular fibrillation in patients with
      normal hearts.
AB  - INTRODUCTION: Ventricular fibrillation (VF) is the main mechanism of sudden
      cardiac death. The clinical precipitants of sudden cardiac death due to
      idiopathic VF are poorly characterized. Emerging evidence implicates triggers
      originating predominantly from the distal Purkinje arborization and the right
      ventricular outflow tract. METHODS AND RESULTS: We report three patients without
      structural heart disease or repolarization abnormalities in whom a febrile
      illness was the only concurrent disease associated with unexpected sudden cardiac
      death due to VF storm. An automated defibrillator was implanted in all three
      patients. In one patient with persistent recurrent VF episodes, mapping
      demonstrated the origin of these triggers was from the Purkinje arborization of
      the anterior wall of the right ventricle. Ablation at a site of earliest
      activation during ectopy, where pace mapping was concordant and Purkinje
      potential preceded the onset of ventriculogram, resulted in suppression of all
      arrhythmias. After follow-up of 22, 9, and 18 months in the three patients, no
      ventricular arrhythmias have been recorded. CONCLUSION: We present a series of
      patients in whom an apparently benign febrile illness was associated with
      malignant ventricular arrhythmias in the absence of cardiac disease or other
      factors known to precipitate sudden cardiac death. Physicians should be aware of
      this possible phenomenon in cases of febrile illness associated with syncope.

PMID- 15574178
TI  - Early morphologic changes following microwave endocardial ablation for treatment
      of chronic atrial fibrillation during mitral valve surgery.
AB  - INTRODUCTION: The aim of this study was to investigate the early qualitative and
      quantitative structural changes in the left atrial wall after endocardial
      microwave ablation in patients with chronic atrial fibrillation (AF) undergoing
      mitral surgery. METHODS AND RESULTS: Seven patients with chronic AF of for at
      least 6 months underwent surgical microwave energy ablation. Linear isolation of
      pulmonary veins was performed in all patients by microwave energy applications to
      the endocardial surface delivered by catheter at 65-W constant power for 45
      seconds. Biopsies were obtained from a selected site (below the right lower
      pulmonary vein) of the left atrial posterior wall before and after the ablation
      procedure in all patients. Control tissues from the same sites were obtained at
      autopsy from patients with noncardiac causes of death. Light and electron
      microscopy was used to examine qualitative and quantitative changes in tissue
      morphology. Tissues after endocardial ablation procedure showed significantly
      increased loss of contractile material. Electron microscopy of atrial tissue
      demonstrated loss of profile of perinuclear and plasma membranes of myocytes,
      disruption of the endothelial cells of capillary vessels, and presence of
      macrophages. CONCLUSION: Lesions created by endocardial microwave energy ablation
      revealed a transmural effect on the left atrial wall without a significant
      reduction in thickness but a significant increase in the myolytic areas involving
      the entire cytosol and occlusion of the small intramyocardial vessels within the
      ablative lesion.

PMID- 15574179
TI  - Effects of resynchronization therapy on cardiac function in pacemaker patients
      "upgraded" to biventricular devices.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) improves echocardiographic
      measures of cardiac function and has a variable effect on QRS duration in
      patients with left bundle branch block (LBBB). How CRT affects these indices in
      patients with right ventricular (RV) pacing-induced LBBB who are "upgraded" with
      left ventricular (LV) leads for CRT is unknown. We studied the echocardiographic
      effects of RV pacing and CRT in patients with prior continuous RV pacing after LV
      lead placement. METHODS AND RESULTS: Fifteen consecutive patients (age 73 +/- 11
      years, LV ejection fraction 24 +/- 6%, QRS duration 190 +/- 27 msec) with New
      York Heart Association class IIIB-IV symptoms and continuous RV pacing underwent
      LV lead placement for CRT. Echocardiography and ECG were performed sequentially
      during RV pacing and CRT. CRT was associated with significantly reduced QRS
      duration (190 +/- 27 msec vs 165 +/- 18 msec, P = 0.005) and reduced LV
      electromechanical delay (180 +/- 33 msec vs 161+/- 43 msec). Baseline QRS
      duration correlated with CRT response. After CRT, patients had significant
      improvements in indices of systolic function, including LV ejection fraction,
      myocardial performance index (MPI), and LV ejection time. Abnormal baseline MPI
      was associated with greater improvement after CRT. LV end-diastolic and systolic
      volumes were similarly decreased with CRT. Mitral valve deceleration time, an
      index of diastolic function, was not affected by CRT. CONCLUSION: "Upgrading" RV
      paced patients with advanced heart failure to CRT improves measures of electrical
      and LV mechanical synchrony and improves systolic function.

PMID- 15574180
TI  - Resynchronization therapy upgrades: turning coach into first class.

PMID- 15574181
TI  - Sinus rhythm electrogram shape measurements are predictive of the origins and
      characteristics of multiple reentrant ventricular tachycardia morphologies.
AB  - INTRODUCTION: During clinical electrophysiologic study, multiple clinical
      tachycardia morphologies often can be induced in the infarct border zone, and all
      morphologies must be targeted for ablation therapy to be successful. Analysis of
      sinus rhythm electrogram shape for localizing figure-of-eight reentrant circuits
      in cases of multiple morphologies is proposed. METHODS AND RESULTS: Sinus rhythm
      activation maps were constructed from bipolar electrograms acquired at 196 to 312
      sites in the epicardial border zone in 10 postinfarction canine hearts. In each
      heart, at least two distinct figure-of-eight reentrant ventricular tachycardia
      morphologies were inducible by premature electrical stimulation, as determined by
      activation maps of sustained tachycardias. Sinus rhythm maps were used to predict
      the location of the isthmus (central common pathway [CCP]), which is the
      protected region of the circuit bounded by arcs of block (mean accuracy 76.7 +/-
      4%). Although reentrant circuits differed, the positions of the entrance point of
      each CCP were common. The location of the line that would span the CCP at its
      narrowest width also was estimated (mean accuracy 91.3 +/- 5%). Ablation at this
      line is expected to prevent reentry recurrence. In one test experiment, ablation
      prevented recurrence of both sustained reentrant tachycardia morphologies.
      CONCLUSION: Sinus rhythm electrogram analyses are useful for (1) localizing
      multiple reentrant circuits with differences in morphology that are inducible by
      premature stimulation in the infarct border zone, and (2) locating and orienting
      the position of a linear lesion for preventing recurrence of all morphologies
      with minimal damage to the heart.

PMID- 15574182
TI  - Comparative pharmacology of guinea pig cardiac myocyte and cloned hERG (I(Kr))
      channel.
AB  - INTRODUCTION: This study used whole-cell, patch clamp techniques on isolated
      guinea pig ventricular myocytes and HEK293 cells expressing cloned human ether-a
      go-go-related gene (hERG) to examine the action of drugs causing QT interval
      prolongation and torsades de pointes (TdP) in man. Similarities and important
      differences in drug actions on cardiac myocytes and cloned hERG I(Kr) channels
      were established. Qualitative actions of the drugs on cardiac myocytes
      corresponded with results obtained from Purkinje fibers and measurement of QT
      interval prolongation in animal and human telemetry studies. METHODS AND RESULTS:
      Adult guinea pig ventricular myocytes were isolated by enzymatic digestion. Cells
      were continuously perfused with Tyrode's solution at 33-35 degrees C. Recordings
      were made using the whole-cell, patch clamp technique. Action potentials (APs)
      were elicited under current clamp. Voltage clamp was used to study the effect of
      drugs on I(Kr) (rapidly activating delayed rectifier potassium current), I(Na)
      (sodium current), and I(Ca) (L-type calcium current). Dofetilide increased the
      myocyte action potential duration (APD) in a concentration-dependent manner, with
      a pIC50 of 7.3. Dofetilide 1 microM elicited early afterdepolarizations (EADs)
      but had little affect on I(Ca) or I(Na). E-4031 increased APD in a concentration
      dependent manner, with a pIC50 of 7.2. In contrast, 10 microM loratadine,
      desloratadine, and cetirizine had little effect on APD or I(Kr). Interestingly,
      cisapride displayed a biphasic effect on myocyte APD and inhibited I(Ca) at 1
      microM. Even at this high concentration, cisapride did not elicit EADs. A number
      of AstraZeneca compounds were tested on cardiac myocytes, revealing a mixture of
      drug actions that were not observed in hERG currents in HEK293 cells. One
      compound, particularly AR-C0X, was a potent blocker of myocyte AP (pIC50 of 8.4).
      AR-C0X also elicited EADs in cardiac myocytes. The potencies of the same set of
      drugs on the cloned hERG channel also were assessed. The pIC50 values for
      dofetilide, E-4031, terfenadine, loratadine, desloratadine, and cetirizine were
      6.8, 7.1, 7.3, 5.1, 5.2, and <4, respectively. Elevation of temperature from 22
      to 35 degrees C significantly enhanced the current kinetics and amplitudes of
      hERG currents and resulted in approximately fivefold increase in E-4031 potency.
      CONCLUSION: Our study demonstrates the advantages of cardiac myocytes over
      heterologously expressed hERG channels in predicting QT interval prolongation and
      TdP in man. The potencies of some drugs in cardiac myocytes were similar to hERG,
      but only myocytes were able to detect important changes in APD characteristics
      and display EADs predictive of arrhythmia development. We observed similar
      qualitative drug profiles in cardiac myocytes, dog Purkinje fibers, and animal
      and human telemetry studies. Therefore, isolated native cardiac myocytes are a
      better predictor of drug-induced QT prolongation and TdP than heterologously
      expressed hERG channels. Isolated cardiac myocytes, when used with high
      throughput patch clamp instruments, may have an important role in screening
      potential cardiotoxic compounds in the early phase of drug discovery. This would
      significantly reduce the attrition rate of drugs entering preclinical and/or
      clinical development. The current kinetics and amplitudes of the cloned hERG
      channel were profoundly affected by temperature, significantly altering the
      potency of one drug (E-4031). This finding cautions against routine drug testing
      at room temperature compared to physiologic temperature when using the cloned
      hERG channel.

PMID- 15574183
TI  - Phytanic acid accumulation is associated with conduction delay and sudden cardiac
      death in sterol carrier protein-2/sterol carrier protein-x deficient mice.
AB  - INTRODUCTION: The sterol carrier protein-2 gene encodes two functionally distinct
      proteins: sterol carrier protein-2 (SCP2, a peroxisomal lipid carrier) and sterol
      carrier protein-x (SCPx, a peroxisomal thiolase known as peroxisomal thiolase-2),
      which is involved in peroxisomal metabolism of bile acids and branched-chain
      fatty acids. We show in this study that mice deficient in SCP2 and SCPx
      (SCP2null) develop a cardiac phenotype leading to a high sudden cardiac death
      rate if mice are maintained on diets enriched for phytol (a metabolic precursor
      of branched-chain fatty acids). METHODS AND RESULTS: In 210 surface and 305
      telemetric ECGs recorded in wild-type (C57BL/6; wt; n = 40) and SCP2 null mice (n
      = 40), no difference was observed at baseline. However, on diet, cycle lengths
      were prolonged in SCP2 null mice (262.9 +/- 190 vs 146.3 +/- 43 msec), AV
      conduction was prolonged (58.3 +/- 17 vs 42.6 +/- 4 ms), and QRS complexes were
      wider (19.1 +/- 5 vs 14.0 +/- 4 ms). In 11 gene-targeted Langendorff-perfused
      hearts isolated from SCP2 null mice after dietary challenge, complete AV blocks
      (n = 5/11) or impaired AV conduction (Wenckebach point 132 +/- 27 vs 92 +/- 10
      msec; P < 0.05) could be confirmed. Monophasic action potentials were not
      different between the two genotypes. Left ventricular function studied by
      echocardiography was similar in both strains. Phytanic acid but not pristanic
      acid accumulated in the phospholipid fraction of myocardial membranes isolated
      from SCP2 null mice. CONCLUSION: Accumulation of phytanic acid in myocardial
      phospholipid membranes is associated with bradycardia and impaired AV nodal and
      intraventricular impulse conduction, which could provide an explanation for
      sudden cardiac death in this model.

PMID- 15574184
TI  - Fatty acid metabolism and arrhythmias.

PMID- 15574185
TI  - Safety and feasibility of cryothermal ablation within the mid- and distal
      coronary sinus.
AB  - INTRODUCTION: The aim of this study was to assess the safety and feasibility of
      catheter-based cryothermal ablation lesions in the mid- and distal coronary
      sinus. METHODS AND RESULTS: Cryothermal ablation lesions were delivered using a 7
      French catheter at the mid- (n = 13) and distal (n = 12) coronary sinus in 14
      swine under general anesthesia. Lesions were delivered for 2 or 4 minutes in a
      1:2 randomized ratio such that seven 2-minute lesions and eighteen 4-minute
      lesions were delivered to a maximum negative temperature of -70 degrees C.
      Integrity of the circumflex artery was assessed by angiography before and after
      each lesion application. In five animals, arterial Doppler flow velocity was
      continuously monitored and coronary flow reserve assessed. Histologic assessment
      of the left AV ring was made after a 48-hour survival period and lesions graded
      for depth and transmurality. Eighteen of 25 lesions were >3 mm deep: five of
      seven 2-minute lesions and thirteen of eighteen 4-minute lesions. Lesions were
      transmural in 18 of 25 cases. Two transmural lesions were limited in depth due to
      their epicardial position. One 2-minute mid-coronary sinus lesion was not found.
      Adherent thrombus was seen grossly in the coronary sinus at one site and only on
      microscopic examination in three other lesions. Angiography demonstrated no
      arterial spasm or thrombosis. Continuous-flow Doppler remained unchanged
      throughout lesion production. Coronary flow reserve was unchanged (1.7 +/- 0.8
      preablation vs 1.7 +/- 1.0 postablation, P = 0.6). The media and intima were
      preserved in all cases. Necrosis of the adventitia was seen in one arterial
      segment. CONCLUSION: Catheter-based cryoablation can produce lesions in the
      musculature of the adjacent atrium and ventricle when accessed from the coronary
      sinus without significant injury to the coronary sinus or adjacent artery. This
      method has potential application as the ablation method of choice when such
      lesions are required.

PMID- 15574186
TI  - Left atrial pacemaker dominance after catheter ablation of atrial fibrillation.
AB  - We report a case of left atrial dominant rhythm demonstrated by electroanatomic
      mapping. The rhythm occurred after radiofrequency catheter ablation in a patient
      with persistent atrial fibrillation and structural heart disease.

PMID- 15574187
TI  - Manifestation of Brugada syndrome after pacemaker implantation in a patient with
      sick sinus syndrome.
AB  - A 49-year-old woman experienced syncope 10 months after DDD pacemaker
      implantation for sick sinus syndrome. ECG revealed abnormal ST elevation in leads
      V1 to V3 during a paced rhythm. Multifocal premature ventricular contractions
      followed by ventricular fibrillation were documented. Saddleback-type ST
      elevation was confirmed after a mode change to AAI. The diagnosis of Brugada
      syndrome was made, and the DDD pacemaker was upgraded to an implantable
      cardioverter defibrillator. Brugada syndrome can be easily overlooked if the
      classic ECG findings are not initially noted but may be observed even during
      pacing therapy.

PMID- 15574188
TI  - Widening of the QRS complex during tachycardia: what is the mechanism?

PMID- 15574189
TI  - Unusual mode of tachycardia termination uncovers the underlying arrhythmia
      mechanism.
AB  - We discuss the differential diagnosis of a tachycardia with a broad QRS complex
      and how the mode of termination helped elucidate the underlying tachycardia
      mechanism.

PMID- 15574190
TI  - Pulmonary vein antrum isolation: intracardiac echocardiography-guided technique.
AB  - Several techniques are used for AF ablation, but no general consensus exists as
      to which technique is the most effective. At our center, we have developed a
      technique for isolating the pulmonary veins (PVs) at their antrum. The technique
      is guided by intracardiac echocardiography (ICE) and mapping with a circular
      (Lasso) catheter. Our technique was developed based on four crucial principles:
      1. Precisely identifying the true border of the PV antrum. 2. Electrically
      isolating all of the PVs at the level of the antrum. 3. Avoiding risk of PV
      stenosis by ablating outside of the antrum. 4. Minimizing risk of other
      complications, such as perforation and stroke, by direct visualization during
      transseptal access and radiofrequency (RF) ablation.

PMID- 15574191
TI  - Pseudo-fascicular activity originating from the right ventricular outflow tract.

PMID- 15574192
TI  - Reexamining the effects of gestational age, fetal growth, and maternal smoking on
      neonatal mortality.
AB  - BACKGROUND: Low birth weight (<2,500 g) is a strong predictor of infant
      mortality. Yet low birth weight, in isolation, is uninformative since it is
      comprised of two intertwined components: preterm delivery and reduced fetal
      growth. Through nonparametric logistic regression models, we examine the effects
      of gestational age, fetal growth, and maternal smoking on neonatal mortality.
      METHODS: We derived data on over 10 million singleton live births delivered at
      >/= 24 weeks from the 1998-2000 U.S. natality data files. Nonparametric
      multivariable logistic regression based on generalized additive models was used
      to examine neonatal mortality (deaths within the first 28 days) in relation to
      fetal growth (gestational age-specific standardized birth weight), gestational
      age, and number of cigarettes smoked per day. All analyses were further adjusted
      for the confounding effects due to maternal age and gravidity. RESULTS: The
      relationship between standardized birth weight and neonatal mortality is
      nonlinear; mortality is high at low z-score birth weights, drops precipitously
      with increasing z-score birth weight, and begins to flatten for heavier infants.
      Gestational age is also strongly associated with mortality, with patterns similar
      to those of z-score birth weight. Although the direct effect of smoking on
      neonatal mortality is weak, its effects (on mortality) appear to be largely
      mediated through reduced fetal growth and, to a lesser extent, through shortened
      gestation. In fact, the association between smoking and reduced fetal growth gets
      stronger as pregnancies approach term. CONCLUSIONS: Our study provides important
      insights regarding the combined effects of fetal growth, gestational age, and
      smoking on neonatal mortality. The findings suggest that the effect of maternal
      smoking on neonatal mortality is largely mediated through reduced fetal growth.

PMID- 15574193
TI  - Caregivers' practices, knowledge and beliefs of antibiotics in paediatric upper
      respiratory tract infections in Trinidad and Tobago: a cross-sectional study.
AB  - BACKGROUND: Antibiotic overuse and misuse for upper respiratory tract infections
      in children is widespread and fuelled by public attitudes and expectations. This
      study assessed knowledge, beliefs, and practices regarding antibiotic use for
      these paediatric infections among children's caregivers' in Trinidad and Tobago
      in the English speaking Caribbean. METHODS: In a cross-sectional observational
      study, by random survey children's adult caregivers gave a telephone interview
      from November 1998 to January 1999. On a pilot-tested evaluation instrument,
      respondents provided information about their knowledge and beliefs of
      antibiotics, and their use of these agents to treat recent episodes (< previous
      30 days) of upper respiratory tract infections in children under their care.
      Caregivers were scored on an antibiotic knowledge test and divided based on their
      score. Differences between those with high and low scores were compared using the
      chi-square test. RESULTS: Of the 417 caregivers, 70% were female and between 18
      40 years, 77% were educated to high school and beyond and 43% lived in urban
      areas. Two hundred and forty nine (60%) respondents scored high (>or12) on
      antibiotic knowledge and 149 (34%) had used antibiotics in the preceding year.
      More caregivers with a high knowledge score had private health insurance (33%),
      (p < 0.02), high school education (57%) (p < 0.002), and had used antibiotics in
      the preceding year (p < 0.008) and within the last 30 days (p < 0.05). Caregivers
      with high scores were less likely to demand antibiotics (p < 0.05) or keep them
      at home (p < 0.001), but more likely to self-treat with antibiotics (p < 0.001).
      Caregivers administered antibiotics in 241/288 (84%) self-assessed severe
      episodes of infection (p < 0.001) and in 59/126 (43%) cough and cold episodes
      without visiting a health clinic or private physician (p < 0.05). CONCLUSIONS: In
      Trinidad and Tobago, caregivers scoring low on antibiotic knowledge have
      erroneous beliefs and use antibiotics inappropriately. Children in their care
      receive antibiotics for upper respiratory tract infections without visiting a
      health clinic or a physician. Educational interventions in the community on the
      consequences of inappropriate antibiotic use in children are recommended. Our
      findings emphasise the need to address information, training, legislation and
      education at all levels of the drug delivery system towards discouraging self
      medication with antibiotics in children.

PMID- 15574194
TI  - Mitochondrial inhibition of uracil-DNA glycosylase is not mutagenic.
AB  - BACKGROUND: Uracil DNA glycosylase (UDG) plays a major role in repair of uracil
      formed due to deamination of cytosine. UDG in human cells is present in both the
      nucleus and mitochondrial compartments. Although, UDG's role in the nucleus is
      well established its role in mitochondria is less clear. RESULTS: In order to
      identify UDG's role in the mitochondria we expressed UGI (uracil glycosylase
      inhibitor) a natural inhibitor of UDG in the mitochondria. Our studies suggest
      that inhibition of UDG by UGI in the mitochondria does not lead to either
      spontaneous or induced mutations in mtDNA. Our studies also suggest that UGI
      expression has no affect on cellular growth or cytochrome c-oxidase activity.
      CONCLUSIONS: These results suggest that human cell mitochondria contain
      alternatives glycosylase (s) that may function as back up DNA repair protein (s)
      that repair uracil in the mitochondria.

PMID- 15574195
TI  - Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a
      biracial population: the Stroke Prevention in Young Women Study.
AB  - BACKGROUND: The genes encoding proteins in the thrombomodulin-protein C pathway
      are promising candidate genes for stroke susceptibility because of their
      importance in thrombosis regulation and inflammatory response. Several published
      studies have shown that the Ala455Val thrombomodulin polymorphism is associated
      with ischemic heart disease, but none has examined the association with stroke.
      Using data from the Stroke Prevention in Young Women Study, we sought to
      determine the association between the Ala455Val thrombomodulin polymorphism and
      the occurrence of ischemic stroke in young women. METHODS: All 59 hospitals in
      the greater Baltimore-Washington area participated in a population-based case
      control study of stroke in young women. We compared 141 cases of first ischemic
      stroke (44% black) among women 15 to 44 years of age with 210 control subjects
      (35% black) who were identified by random digit dialing and frequency matched to
      the cases by age and geographical region of residence. Data on historical risk
      factors were collected by standardized interview. Genotyping of the
      thrombomodulin Ala455Val polymorphism was performed by pyrosequencing. RESULTS:
      The A allele (frequency = 0.85) was associated with stroke under the recessive
      model. After adjustment for age, race, cigarette smoking, hypertension, and
      diabetes, the AA genotype, compared with the AV and VV genotypes combined, was
      significantly associated with stroke (odds ratio 1.9, 95% CI 1.1-3.3). The AA
      genotype was more common among black than white control subjects (81% versus 68%)
      but there was no significant interaction between the risk genotype and race
      (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis
      removing all probable (n = 16) and possible (n = 15) cardioembolic strokes
      demonstrated an increased association (odds ratio 2.2, 95% CI 1.2-4.2).
      CONCLUSIONS: Among women aged 15 to 44 years, the AA genotype is more prevalent
      among blacks than whites and is associated with increased risk of early onset
      ischemic stroke. Removing strokes potentially related to cardioembolic phenomena
      increased this association. Further studies are needed to determine whether this
      polymorphism is functionally related to thrombomodulin expression or whether the
      association is due to population stratification or linkage to a nearby functional
      polymorphism.

PMID- 15574196
TI  - Progression of coronary calcification in healthy postmenopausal women.
AB  - BACKGROUND: Coronary artery calcium score incrementally improves coronary risk
      prediction beyond that provided by conventional risk factors. Limited information
      is available regarding rates of progression of coronary calcification in women,
      particularly those with baseline scores above zero. Further, determinants of
      progression of coronary artery calcification in women are not well understood.
      This study prospectively evaluated rates and determinants of progression of
      coronary artery calcium score in a group of healthy postmenopausal women.
      METHODS: We determined coronary calcium score by computed tomography and recorded
      demographic, lifestyle and health characteristics of 914 postmenopausal women, a
      subset of those enrolled in the Women's Health Initiative Observational Study.
      The 305 women with calcium score >or=10 Agatston units at baseline were invited
      for repeat scan. This analysis includes the 94 women who underwent second scans.
      RESULTS: Mean age of study participants was 65 +/- 9 years (mean +/- SD), body
      mass index was 26.1 +/- 6.1 kg/m2, and baseline calcium score was 162 +/- 220
      Agatston units. Mean interval between scans was 3.3 +/- 0.7 years. A wide range
      of changes in coronary calcium score was observed, from -53 to +452 Agatston
      units/year. Women with lower scores at baseline had smaller annual increases in
      absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston
      units/year among women with baseline calcium score in the lowest, middle and
      highest tertiles. In multivariate analysis, age was not an independent predictor
      of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A
      reductase inhibitor (statin) use at baseline was a negative predictor (p =
      0.015), whereas baseline calcium score was a strong, positive predictor (p <
      0.0001) of progression of coronary calcification. CONCLUSION: Among
      postmenopausal women with coronary calcium score >or= 10 Agatston units, rates of
      change of coronary calcium score varied widely. In multivariate analysis, statin
      use was a negative independent determinant, whereas baseline calcium score was a
      strong positive predictor of annual change in coronary calcium score.

PMID- 15574197
TI  - Current practices in spatial analysis of cancer data: data characteristics and
      data sources for geographic studies of cancer.
AB  - The use of spatially referenced data in cancer studies is gaining in prominence,
      fueled by the development and availability of spatial analytic tools and the
      broadening recognition of the linkages between geography and health. We provide
      an overview of some of the unique characteristics of spatial data, followed by an
      account of the major types and sources of data used in the spatial analysis of
      cancer, including data from cancer registries, population data, health surveys,
      environmental data, and remote sensing data. We cite numerous examples of recent
      studies that have used these data, with a focus on etiological research.

PMID- 15574198
TI  - Blood coagulation and the risk of atherothrombosis: a complex relationship.
AB  - The principles of Virchov's triad appear to be operational in atherothrombosis or
      arterial thrombosis: local flow changes and particularly vacular wall damage are
      the main pathophysiological elements. Furthermore, alterations in arterial blood
      composition are also involved although the specific role and importance of blood
      coagulation is an ongoing matter of debate. In this review we provide support for
      the hypothesis that activated blood coagulation is an essential determinant of
      the risk of atherothrombotic complications. We distinguish two phases in
      atherosclerosis: In the first phase, atherosclerosis develops under influence of
      "classical" risk factors, i.e. both genetic and acquired forces. While
      fibrinogen/fibrin molecules participate in early plaque lesions, increased
      activity of systemic coagulation is of no major influence on the risk of arterial
      thrombosis, except in rare cases where a number of specific procoagulant forces
      collide. Despite the presence of tissue factor - factor VII complex it is
      unlikely that all fibrin in the atherosclerotic plaque is the direct result from
      local clotting activity. The dominant effect of coagulation in this phase is
      anticoagulant, i.e. thrombin enhances protein C activation through its binding to
      endothelial thrombomodulin.The second phase is characterized by advancing
      atherosclerosis, with greater impact of inflammation as indicated by an elevated
      level of plasma C-reactive protein, the result of increased production influenced
      by interleukin-6. Inflammation overwhelms protective anticoagulant forces, which
      in itself may have become less efficient due to down regulation of thrombomodulin
      and endothelial cell protein C receptor (EPCR) expression. In this phase, the
      inflammatory drive leads to recurrent induction of tissue factor and assembly of
      catalytic complexes on aggregated cells and on microparticles, maintaining a
      certain level of thrombin production and fibrin formation. In advanced
      atherosclerosis systemic and vascular wall driven coagulation becomes more
      important and elevated levels of D-dimer fragments should be interpreted as
      markers of this hypercoagulability.

PMID- 15574199
TI  - Which is the best lipid-modifying strategy in metabolic syndrome and diabetes:
      fibrates, statins or both?
AB  - Although less clinical intervention studies have been performed with fibrates
      than with statins, there are evidences indicating that fibrates may reduce risk
      of cardiovascular events. The potential clinical benefit of the fenofibrate will
      be specified by the ongoing Fenofibrate Intervention and Event Lowering in
      Diabetes (FIELD) study, which rationale, methods and aims have been just
      published. Controlled clinical trials show similar or even greater cardiovascular
      benefits from statins-based therapy in patient subgroups with diabetes compared
      with overall study populations. Therefore, statins are the drug of first choice
      for aggressive lipid lowering actions and reducing risk of coronary artery
      disease in these patients. However, current therapeutic use of statins as
      monotherapy is still leaving many patients with mixed atherogenic dyslipidemia at
      high risk for coronary events. A combination statin/fibrate therapy may be often
      necessary to control all lipid abnormalities in patients with metabolic syndrome
      and diabetes adequately, since fibrates provide additional important benefits,
      particularly on triglyceride and HDL-cholesterol levels. Thus, this combined
      therapy concentrates on all the components of the mixed dyslipidemia that often
      occurs in persons with diabetes or metabolic syndrome, and may be expected to
      reduce cardiovascular morbidity and mortality. Safety concerns about some
      fibrates such as gemfibrozil may lead to exaggerate precautions regarding fibrate
      administration and therefore diminish the use of the seagents. However, other
      fibrates, such as bezafibrate and fenofibrate appear to be safer and better
      tolerated. We believe that a proper co-administration of statins and fibrates,
      selected on basis of their safety, could be more effective in achieving a
      comprehensive lipid control as compared with monotherapy.

PMID- 15574201
TI  - Survival of patients treated with intra-aortic balloon counterpulsation at a
      tertiary care center in Pakistan - patient characteristics and predictors of in
      hospital mortality.
AB  - BACKGROUND: Intra-aortic balloon counterpulsation (IABC) has an established role
      in the treatment of patients presenting with critical cardiac illnesses,
      including cardiogenic shock, refractory ischemia and for prophylaxis and
      treatment of complications of percutaneous coronary interventions (PCI). Patients
      requiring IABC represent a high-risk subset with an expected high mortality.
      There are virtually no data on usage patterns as well as outcomes of patients in
      the Indo-Pakistan subcontinent who require IABC. This is the first report on a
      sizeable experience with IABC from Pakistan. METHODS: Hospital charts of 95
      patients (mean age 58.8 (+/- 10.4) years; 78.9% male) undergoing IABC between
      2000-2002 were reviewed. Logistic regression was used to determine univariate and
      multivariate predictors of in-hospital mortality. RESULTS: The most frequent
      indications for IABC were cardiogenic shock (48.4%) and refractory ischemia
      (24.2%). Revascularization (surgical or PCI) was performed in 74 patients
      (77.9%). The overall in-hospital mortality rate was 34.7%. Univariate predictors
      of in-hospital mortality included (odds ratio [95% CI]) age (OR 1.06 [1.01-1.11]
      for every year increase in age); diabetes (OR 3.68 [1.51-8.92]) and cardiogenic
      shock at presentation (OR 4.85 [1.92-12.2]). Furthermore, prior CABG (OR 0.12
      [0.04-0.34]), and in-hospital revascularization (OR 0.05 [0.01-0.189]) was
      protective against mortality. In the multivariate analysis, independent
      predictors of in-hospital mortality were age (OR 1.13 [1.05-1.22] for every year
      increase in age); diabetes (OR 6.35 [1.61-24.97]) and cardiogenic shock at
      presentation (OR 10.0 [2.33-42.95]). Again, revascularization during
      hospitalization (OR 0.02 [0.003-0.12]) conferred a protective effect. The overall
      complication rate was low (8.5%). CONCLUSIONS: Patients requiring IABC represent
      a high-risk group with substantial in-hospital mortality. Despite this high
      mortality, over two-thirds of patients do leave the hospital alive, suggesting
      that IABC is a feasible therapeutic device, even in a developing country.

PMID- 15574200
TI  - CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa
      cell tumors (GCTs) of ovarian origin.
AB  - BACKGROUND: Granulosa cell tumors (GCTs) are relatively rare and are subtypes of
      the sex-cord stromal neoplasms. Methylation induced silencing in the promoters of
      genes such as tumor suppressor genes, DNA repair genes and pro-apoptotic genes is
      recognised as a critical factor in cancer development. METHODS: We examined the
      role of promoter hypermethylation, an epigenetic alteration that is associated
      with the silencing tumor suppressor genes in human cancer, by studying 5 gene
      promoters in 25 GCTs cases by methylation specific PCR and RT-PCR. In addition,
      the compatible tissues (normal tissues distant from lesion) from three non
      astrocytoma patients were also included as the control. RESULTS: Frequencies of
      methylation in GCTs were 7/25 (28 % for FHIT), 6/25 (24% for FNACF), 3/25 (12%
      for Cyclin D2), 1/25 (4% for BRCA2) and 14/25 (56%) in RUNX3 genes. Correlation
      of promoter methylation with clinical characteristics and other genetic changes
      revealed that overall promoter methylation was higher in more advanced stage of
      the disease. Promoter methylation was associated with gene silencing in GCT cell
      lines. Treatment with methylation or histone deacetylation-inhibiting agents
      resulted in profound reactivation of gene expression. CONCLUSIONS: These results
      may have implications in better understanding the underlying epigenetic
      mechanisms in GCT development, provide prognostic indicators, and identify
      important gene targets for treatment.

PMID- 15574202
TI  - Haplotype frequency estimation error analysis in the presence of missing genotype
      data.
AB  - BACKGROUND: Increasingly researchers are turning to the use of haplotype analysis
      as a tool in population studies, the investigation of linkage disequilibrium, and
      candidate gene analysis. When the phase of the data is unknown, computational
      methods, in particular those employing the Expectation-Maximisation (EM)
      algorithm, are frequently used for estimating the phase and frequency of the
      underlying haplotypes. These methods have proved very successful, predicting the
      phase-known frequencies from data for which the phase is unknown with a high
      degree of accuracy. Recently there has been much speculation as to the effect of
      unknown, or missing allelic data - a common phenomenon even with modern automated
      DNA analysis techniques - on the performance of EM-based methods. To this end an
      EM-based program, modified to accommodate missing data, has been developed,
      incorporating non-parametric bootstrapping for the calculation of accurate
      confidence intervals. RESULTS: Here we present the results of the analyses of
      various data sets in which randomly selected known alleles have been relabelled
      as missing. Remarkably, we find that the absence of up to 30% of the data in both
      biallelic and multiallelic data sets with moderate to strong levels of linkage
      disequilibrium can be tolerated. Additionally, the frequencies of haplotypes
      which predominate in the complete data analysis remain essentially the same after
      the addition of the random noise caused by missing data. CONCLUSIONS: These
      findings have important implications for the area of data gathering. It may be
      concluded that small levels of drop out in the data do not affect the overall
      accuracy of haplotype analysis perceptibly, and that, given recent findings on
      the effect of inaccurate data, ambiguous data points are best treated as unknown.

PMID- 15574203
TI  - Atypical presentation of hepatocellular carcinoma: a mass on the left thoracic
      wall.
AB  - BACKGROUND: Hepatocellular carcinoma is a common malignancy for which chronic
      hepatitis B infection has been defined as the most common etiologic factor. The
      most frequent metastatic sites are the lung, bone, lymphatics, and brain,
      respectively. Metastases to the chest wall have been reported only rarely. CASE
      PRESENTATION: We report a patient with hepatocellular carcinoma who presented
      with an isolated metastatic mass on the left anterolateral chest wall in the
      axillary region. CONCLUSIONS: Metastasis of HCC should be included in the
      differential diagnosis of rapidly growing lesions in unusual localizations,
      particularly in patients with chronic liver disease even if a primary tumor can
      not be radiologically identified.

PMID- 15574204
TI  - Search for computational modules in the C. elegans brain.
AB  - BACKGROUND: Does the C. elegans nervous system contain multi-neuron computational
      modules that perform stereotypical functions? We attempt to answer this question
      by searching for recurring multi-neuron inter-connectivity patterns in the C.
      elegans nervous system's wiring diagram. RESULTS: Our statistical analysis
      reveals that some inter-connectivity patterns containing two, three and four (but
      not five) neurons are significantly over-represented relative to the expectations
      based on the statistics of smaller inter-connectivity patterns. CONCLUSIONS: Over
      represented patterns (or motifs) are candidates for computational modules that
      may perform stereotypical functions in the C. elegans nervous system. These
      modules may appear in other species and need to be investigated further.

PMID- 15574205
TI  - Early carotid artery stenting and angioplasty in patients with acute ischemic
      stroke.
AB  - OBJECTIVE: To determine the safety of early percutaneous endovascular carotid
      angioplasty and stenting (CAS) after an ischemic stroke. METHODS: The
      neurointerventional database was reviewed for patients who underwent CAS after an
      acute ischemic stroke in two university hospitals. Clinical and radiological data
      were reviewed. Outcomes were worsening stroke, new stroke, or stroke-related
      death up to 30 days after the procedure. Procedure-related complications were
      also documented. RESULTS: A total of 38 patients with 39 procedures were
      identified. The mean age was 67 +/- 15 years; 31 of 38 patients were Caucasian
      and 24 were female. Hypertension was found in 21 patients, peripheral vascular
      disease in 12, diabetes in 13, and coronary artery disease in 18. The median
      initial National Institutes of Health Stroke Scale score was 8. The carotid
      artery showed severe to high-grade stenosis in 28 patients, dissection was
      present in 6, and the rest had an acute occlusion treated with thrombolysis
      followed by CAS. The mean time from stroke onset to CAS was 55 +/- 34 hours. The
      mean degree of stenosis at baseline was 86 +/- 11%. In 37 procedures, complete
      recanalization was achieved, defined as less than 10% residual narrowing; in 2
      procedures, the residual stenosis was mild (10-20%). Neurological deterioration
      occurred after three procedures (7.7%), with minor nondisabling stroke in two and
      death from intracranial hemorrhage in one. CONCLUSION: If deemed necessary and in
      certain circumstances, early CAS seems to be safe after acute ischemic stroke if
      infarction volume is small and neurological deficit is mild.

PMID- 15574206
TI  - Cardiac injury after subarachnoid hemorrhage is independent of the type of
      aneurysm therapy.
AB  - OBJECTIVE: Subarachnoid hemorrhage (SAH) is associated with cardiac injury and
      dysfunction. Whether aneurysm clipping versus coiling has a differential effect
      on the risk of troponin release and left ventricular (LV) dysfunction after SAH
      is unknown. It is hypothesized that aneurysm treatment does not affect the risk
      of developing cardiac injury and dysfunction. METHODS: The study included 172
      consecutive SAH patients who underwent clipping (n = 109) or coiling (n = 63)
      aneurysm therapy. Hemodynamic data were collected, cardiac troponin I was
      measured, and echocardiography was performed on the 1st, 3rd, and 6th days after
      enrollment. A cardiac troponin I measurement of more than 1.0 microg/L was
      considered abnormal. For each echocardiographic examination, a blinded observer
      measured LV ejection fraction (abnormal if <50%) and quantified LV regional wall
      motion abnormalities. The incidence of cardiac outcomes in the treatment groups
      was compared using odds ratios (ORs). RESULTS: The coiled patients were older
      than the clipped patients (mean age, 59 +/- 13 yr versus 53 +/- 12 yr; t test, P
      < 0.001) and were more likely to have posterior aneurysms (33% versus 18%; chi(2)
      test, P = 0.019). There were no significant between-group differences in the risk
      of cardiac troponin I release (coil 21% versus clip 19%; OR = 0.89, P = 0.789),
      regional wall motion abnormalities (33% versus 28%; OR = 0.76, P = 0.422), or LV
      ejection fraction lower than 50% (16% versus 17%; OR = 1.06, P = 0.892). No
      patient died of cardiac causes (heart failure, myocardial infarction, or
      arrhythmia). CONCLUSION: Surgical and endovascular aneurysm therapies were
      associated with similar risks of cardiac injury and dysfunction after SAH. The
      presence of neurocardiogenic injury should not affect aneurysm treatment
      decisions.

PMID- 15574207
TI  - Radiotherapeutic factors in the management of cervical-basal chordomas and
      chondrosarcomas.
AB  - OBJECTIVE: To define prognostic factors for local control and survival in 90
      consecutive patients treated by fractionated photon and proton radiation for
      chordoma or chondrosarcoma of the cranial base and upper cervical spine. METHODS:
      Between December 1995 and December 2000, 90 patients (median age, 51.3 yr; range,
      10-85 yr; male/female ratio, 3:2) were treated by a combination of high-energy
      photons and protons. Sixty-four patients had a chordoma, and 26 had a
      chondrosarcoma. The proton component was delivered by the 201-MeV proton beam of
      the Centre de Protontherapie d'Orsay. The median total dose delivered to the
      gross tumor volume (GTV) was 67 cobalt Gray equivalents (range, 22-70 cobalt Gray
      equivalents). RESULTS: With a median follow-up of 34 months (range, 3-74 mo),
      treatment of 25 tumors failed locally. The 3-year local control rates were 69.2%
      (+/-6.0%) and 91.6% (+/-8.4%) for chordomas and chondrosarcomas, respectively.
      According to multivariate analysis, a small tumor volume excluded from the 95%
      isodose line (P = 0.032; relative risk [RR], 0.098; 95% confidence interval [CI],
      0.01-0.81) and a controlled tumor (P = 0.049; RR, 0.19; 95% CI, 0.04-0.99) were
      independent favorable prognostic factors for overall survival. On multivariate
      analysis, a high minimum dose (P = 0.02; RR, 2.8; 95% CI, 1.2-6.6), a high tumor
      control probability (P = 0.02; RR, 3.8; 95% CI, 1.2-12.5), a high dose delivered
      to 95% of the GTV (P = 0.03; RR, 3.4; 95% CI, 1.15-10.2), a high GTV encompassed
      by the 90% isodose line (P = 0.01; RR, 3.29; 95% CI, 1.29-8.44), and a small GTV
      excluded from the 90% isodose line (P = 0.036; RR, 0.4; 95% CI, 0.1-0.9) were
      independent favorable prognostic factors for local control. CONCLUSION: In
      chordomas and chondrosarcomas of the cranial base and cervical spine treated by
      surgical resection and then by high-dose photon and proton irradiation, local
      control is mainly dependent on the quality of radiation, especially dose
      uniformity within the GTV. Special attention must be paid to minimize underdosed
      areas because of the close proximity of critical structures and to redefine and
      possibly escalate dose constraints to tumor targets in future studies in view of
      the low toxicity observed to date.

PMID- 15574208
TI  - Meningiomas invading the superior sagittal sinus: surgical experience in 108
      cases.
AB  - OBJECTIVE: Radical resection of meningiomas invading the superior sagittal sinus
      (SSS) presents several hazards. Some surgeons consider SSS invasion a
      contraindication for complete resection, and others advocate total resection with
      venous reconstruction. There is a lack of published large series to provide
      definitive guidelines for the surgical treatment of these complex cases. We
      report our 15-year experience with surgery of parasagittal meningiomas invading
      the SSS. METHODS: Between 1986 and 2001, 108 patients (73 women, 35 men; age
      range, 22-83 yr; mean age, 56.2 yr) underwent surgery at the Neurological
      Institute "C. Besta" of Milan for tumors invading the SSS. Parasagittal
      meningiomas not invading the SSS were excluded from this series. RESULTS: Simpson
      Grade I to II removal was achieved in 100 patients. Thirty patients with
      meningiomas totally occluding the SSS had complete resection of the encased
      portion of the sinus. Histological examination revealed 86 benign (79.6%), 16
      atypical (14.8%), and 4 malignant (3.7%) meningiomas along with 2
      hemangiopericytomas. There were two perioperative deaths. Serious complications
      included brain swelling (nine patients; 8.3%) and postoperative hematoma (two
      patients; 1.85%). Follow-up ranged from 19 to 223 months (mean, 79.5 mo). One
      patient was lost to follow-up. Tumors recurred in 15 patients (13.9%). After
      multivariate analysis, histological type, tumor size, and Simpson grade were
      confirmed as significant independent prognostic factors for recurrence.
      CONCLUSION: On the basis of our results, we conclude that if the sinus is
      partially invaded, it can be opened to obtain as complete a resection as possible
      and to attempt to preserve the patency of the sinus. If the sinus is obstructed,
      the portion of the sinus involved can be resected completely. In both situations,
      extreme care is vital to preservation of cortical veins, which may offer
      important collateral drainage. With our approach, good results are achieved and
      it is not necessary to reconstruct the sinus.

PMID- 15574209
TI  - Spinal en plaque meningiomas: a contemporary experience.
AB  - OBJECTIVE: Spinal en plaque meningiomas are rare and challenging lesions because
      of their tendency to induce spinal arachnoiditis. The surgical treatment of this
      type of meningioma is more complex than that of classic meningioma. METHODS: We
      report seven cases of spinal en plaque meningiomas and review all the cases
      reported in the literature accessible to us by a MEDLINE search. RESULTS: All
      patients underwent microsurgery. Complete tumor removal was achieved in three
      patients. Subtotal removal was performed in four patients. A permanent
      neurological worsening was observed in one patient. CONCLUSION: Spinal
      meningiomas en plaque bear a prognosis poorer than that of classic meningiomas
      with regard to the possibility of a definitive surgical cure because recurrence
      or postoperative arachnoiditis occurs frequently. Total surgical removal should
      be attempted only when a clear plane of cleavage between tumor and arachnoid
      exists.

PMID- 15574210
TI  - [18F]fluorodeoxyglucose-positron emission tomography in patients with
      medulloblastoma.
AB  - OBJECTIVE: We evaluated the [(18)F]fluorodeoxyglucose (FDG) accumulation during
      positron emission tomography (PET) in patients with medulloblastoma and examined
      the relationship of intensity of uptake with patient outcome after the initial
      scan. METHODS: Magnetic resonance imaging and FDG-PET scans of brain and spine
      were used to assess FDG uptake by visual grade (qualitative analysis) and
      metabolic activity ratios (T(max)/G(mean) and T(max)/W(mean)). Patients were
      divided into two groups based on either confirmation of tumor by biopsy and/or
      death resulting from progressive disease after the initial FDG-PET scan (Group A)
      or no intervention for the suspected lesion shown on magnetic resonance imaging
      after the initial FDG-PET scan but currently alive without evidence of disease
      (Group B). RESULTS: Twenty-two patients with either recurrent (n = 21) or newly
      diagnosed (n = 1) medulloblastoma underwent brain (n = 18) or whole-body (n = 4)
      FDG-PET scans after magnetic resonance imaging evidence of suspected tumor. The
      median qualitative analysis was 3 (range, 0-4) in 17 Group A patients compared
      with 0 (range, 0-1) in 5 Group B patients (P = 0.0003). The mean T(max)/G(mean)
      and T(max)/W(mean) ratios for 16 Group A patients were 1.3 (range, 0.1-3.8) and
      2.10 (range, 0.4-5.2), respectively, compared with 0.80 (range, 0.20-1.5) and 1.3
      (range, 0.5-1.9) in 5 Group B patients (P = 0.2 for both parameters, not
      significant). There was a significant negative correlation between increased FDG
      uptake and survival. Higher qualitative analysis and T(max)/W(mean) were
      associated with significantly poorer 2-year overall survival after the initial
      scan (71% versus 15% for qualitative analysis grade of <3 versus > or =3, P =
      0.001; 46% versus 0% for T(max)/W(mean) < or =2.5 versus >2.5, P = 0.004).
      CONCLUSION: Increased FDG uptake is observed in medulloblastoma and is correlated
      negatively with survival.

PMID- 15574211
TI  - Concussion in professional football: neuropsychological testing--part 6.
AB  - OBJECTIVE: The National Football League (NFL) neuropsychological testing program
      is reviewed, and neuropsychological test data are presented on various samples of
      NFL athletes who sustained concussion (mild traumatic brain injury, MTBI).
      METHODS: This study evaluated post-MTBI neuropsychological testing of NFL players
      from 1996 to 2001. All athletes completed a standardized battery of
      neuropsychological tests and underwent postinjury neuropsychological testing
      within a few days after concussion. Test scores were compared with baselines
      using analysis of variance for athletes having on-field memory dysfunction, three
      or more concussions, or 7+ days out from practice and play. RESULTS: The MTBI
      group did not display significant neuropsychological dysfunction relative to
      baseline scores within a few days of injury. However, a subsample of the injured
      athletes who displayed on-field memory dysfunction performed significantly more
      poorly on two of the memory tests. The neuropsychological test results of a group
      of athletes with a history of three or more MTBIs did not differ significantly
      compared with a group who had fewer than three concussions or compared with
      league-wide normative data. The neuropsychological performance of athletes who
      were out from full participation 7+ days was not significantly different from the
      group who returned to play within 7 days or the norms. CONCLUSION:
      Neuropsychological testing is used within the overall medical evaluation and care
      of NFL athletes. Players who experience MTBI generally demonstrate rapid recovery
      of neuropsychological performance, although poorer neuropsychological test
      results were related to on-field memory dysfunction. NFL players did not
      demonstrate evidence of neurocognitive decline after multiple (three or more)
      MTBIs or in those players out 7+ days. The data show that MTBI in this population
      is characterized by a rapid return of neuropsychological function in the days
      after injury.

PMID- 15574212
TI  - Subcortical white matter metabolic changes remote from focal hemorrhagic lesions
      suggest diffuse injury after human traumatic brain injury.
AB  - OBJECTIVE: We used positron emission tomographic studies to prospectively examine
      the relationship between glucose and oxidative metabolism in the subcortical
      white matter (WM) acutely after traumatic brain injury (TBI). The objective was
      to determine the nature, extent, and degree of metabolic abnormalities in
      subcortical brain regions remote from hemorrhagic lesions. METHODS: Sixteen
      normal volunteers and 10 TBI patients (Glasgow Coma Scale score, 4-10; age, 17-64
      yr; 6 with focal and 4 with diffuse injury) were studied. Each subject underwent
      dynamic positron emission tomographic studies using [(15)O]CO, (15)O(2),
      [(15)O]H(2)O, and fluorodeoxyglucose plus a magnetic resonance imaging scan
      acutely after TBI. Parametric images of the metabolic rate of oxygen and
      metabolic rate of glucose were generated, and a molar oxygen-to-glucose
      utilization ratio was calculated. Data from gray matter and WM remote from
      hemorrhagic lesions, plus whole brain, were analyzed. RESULTS: There was a
      significant reduction in the subcortical WM oxygen-to-glucose utilization ratio
      after TBI compared with normal values (3.99 +/- 0.77 versus 5.37 +/- 1.00; P <
      0.01), whereas the mean cortical gray matter and whole-brain values remained
      unchanged. WM metabolic changes, which were diffuse throughout the hemispheres,
      were characterized by a reduction in the metabolic rate of oxygen without a
      concomitant drop in the metabolic rate of glucose. CONCLUSION: The extent and
      degree of subcortical WM metabolic abnormalities after moderate and severe TBI
      suggest that diffuse WM injury is a general phenomenon after such injuries. This
      pervasive finding may indicate that the concept of focal traumatic injury,
      although valid from a computed tomographic imaging standpoint, may be misleading
      when considering metabolic derangements associated with TBI.

PMID- 15574213
TI  - Evolution of brain tissue injury after evacuation of acute traumatic subdural
      hematomas.
AB  - OBJECTIVE: Acute traumatic subdural hematoma complicated by brain parenchymal
      injury is associated with a 60 to 90% mortality rate. Early surgical evacuation
      of the mass lesion is essential for a favorable outcome, but the severity of the
      underlying brain injury determines the outcome, even when surgery has been
      prompt. The purpose of this study was to analyze tissue biochemical patterns in
      the brain underlying an evacuated acute subdural hematoma to identify a
      characteristic pattern of changes that might indicate evolving brain injury.
      METHODS: Prospectively collected data from 33 patients after surgical evacuation
      of acute subdural hematoma were analyzed. Both a brain tissue oxygen tension
      probe and an intracerebral microdialysis probe were placed in brain tissue
      exposed at surgery. On the basis of the postoperative clinical course, the
      patients were divided into three groups: patients with early intractable
      intracranial hypertension, patients with evolution of delayed traumatic injury
      (DTI), and patients with an uncomplicated course (the no-DTI group). RESULTS: The
      overall mortality rate was 46%, with 100% mortality in the intracranial
      hypertension group (five patients). Mortality in the DTI group was 53% compared
      with only 9% in the no-DTI group (P = 0.002). There were no significant
      differences in the initial computed tomographic scan characteristics, such as
      thickness of the subdural hematoma or amount of midline shift, among the three
      groups. Physiological variables, as well as the microdialysate measures of brain
      biochemistry, were markedly different in the intracranial hypertension group
      compared with the other groups. Differences between the other two groups were
      more subtle but were significant. Significantly lower values of brain tissue
      oxygen tension (14 +/- 8 mm Hg versus 27 +/- 14 mm Hg) and higher dialysate
      values of lactate and pyruvate were documented in patients who developed a
      delayed injury compared with patients with uncomplicated courses (4.1 +/- 2.3
      mmol/L versus 1.7 +/- 0.7 mmol/L for lactate, and 104 +/- 47 micromol/L versus 73
      +/- 54 micromol/L for pyruvate at 24 h after injury). CONCLUSION: Evolution of
      DTI in the area of brain underlying an evacuated subdural hematoma is associated
      with a significant increase in mortality. Postoperatively decreasing brain tissue
      oxygen tension and increasing dialysate concentrations of lactate and pyruvate in
      this area may warn of evolving brain injury and evoke further diagnostic and
      therapeutic activity.

PMID- 15574214
TI  - Spinal cord injury without radiographic abnormality in children, 2 decades later.
AB  - OBJECTIVE: Much new research has emerged since 1982, when the original
      description of spinal cord injury without radiographic abnormality (SCIWORA) as a
      self-contained syndrome was reported. This article reviews new and old data on
      SCIWORA, from the past 2 decades. METHODS: This article reviews what we have
      learned since 1982 about the unique biomechanical properties of the juvenile
      spine, the mechanisms of injuries, the profound influence of age on injury
      pattern and outcome, the magnetic resonance imaging (MRI) features, and
      management algorithms of SCIWORA. RESULTS: The increasing use of MRI in SCIWORA
      has yielded ample evidence of damage in virtually all nonbony supporting tissues
      of the juvenile vertebral column, including rupture of the anterior and posterior
      longitudinal ligaments, intervertebral disc disruption, muscular and interspinal
      ligament tears, tectorial membrane rupture, and shearing of the subepiphyseal
      growth zone of the vertebral endplates. These findings provide the structural
      basis for the postulated "occult instability" in the spine of a patient after
      SCIWORA. MRI also demonstrated five classes of post-SCIWORA cord findings:
      complete transection, major hemorrhage, minor hemorrhage, edema only, and normal.
      These "neural" findings are highly predictive of outcome: patients with
      transection and major hemorrhage had profoundly poor outcome, but 40% with minor
      hemorrhage improved to mild grades, whereas 75% with "edema only" attained mild
      grades and 25% became normal. All patients with normal cord signals made complete
      recovery. The large pool of clinical data from our own and other centers also
      lends statistical power to uphold most of our original assertions regarding
      incidence, causes of injury, pathophysiology, age-related changes in the
      malleability of the spine, vectors of deformation, and the extreme vulnerability
      of young children to severe cord injury, particularly high cervical cord injury.
      Thoracic SCIWORA has been identified as an important subset, comprising three
      subtypes involving high-speed direct impact, distraction from lap belts, and
      crush injury by slow moving vehicles. Computation of the sensitivities of MRI and
      somatosensory evoked potentials in detecting SCIWORA shows that both tests were
      normal in 12 to 15% of children with definite, persistent myelopathy; all of
      these children were nevertheless braced for 3 months because of their clinical
      syndrome. Children with transient deficits but abnormal MRI and/or somatosensory
      evoked potentials were also braced, but the 60% with transient deficits and
      normal MRI and somatosensory evoked potentials were not braced. This is a change
      from our original policy in 1982 of bracing all children with persistent or
      transient deficits, brought on by our new MRI and electrophysiology data.
      CONCLUSION: Injury prevention, prompt recognition, use of MRI and
      electrophysiological verification, and timely bracing of SCIWORA patients remain
      the chief measures to improve outcome.

PMID- 15574215
TI  - Evaluating the effect of decompression surgery on cerebrospinal fluid flow and
      intracranial compliance in patients with chiari malformation with magnetic
      resonance imaging flow studies.
AB  - OBJECTIVE: To quantify the effect of decompression surgery on craniocervical
      junction hydrodynamics and on global intracranial compliance (ICC) in patients
      with Chiari I malformation by use of magnetic resonance measurements of
      cerebrospinal fluid and blood flow. Studying the effect of decompression surgery
      may improve our understanding of the pathophysiological characteristics of Chiari
      I malformation and aid in identifying patients who will benefit from the
      procedure. METHODS: Twelve patients were studied with a 1.5-T magnetic resonance
      imaging scanner before and after decompression surgery. Cine phase contrast
      magnetic resonance images were used to quantify maximum cord displacement,
      maximum systolic cerebrospinal fluid velocity and volumetric flow rate, and
      overall ICC. ICC was derived by use of a previously reported method that measures
      small changes in intracranial volume and pressure that occur naturally with each
      cardiac cycle. RESULTS: After surgery, changes were documented both in the local
      hydrodynamic parameters and in ICC. However, only the change in ICC, an average
      increase of more than 60%, was statistically significant. Increased ICC, which
      was associated with improved outcome, was measured in 10 of the 12 patients, no
      significant change was documented in 1 patient, and decreased ICC was measured in
      1 patient whose symptoms persisted after surgery. CONCLUSION: An increase in the
      overall compliance of the intracranial compartment is the most significant and
      consistent change measured after decompression surgery. Changes in cord
      displacement, cerebrospinal fluid velocities, and flow in the craniospinal
      junction were less consistent and less affected by the operation. Thus, ICC may
      play an important role in the outcome of decompression surgery related to
      improving symptoms and restoring normal neurological hydrodynamics in patients
      with Chiari I malformations.

PMID- 15574216
TI  - Spinal intradural juxtamedullary cysts in the adult: surgical management and
      outcome.
AB  - OBJECTIVE: Intradural nonneoplastic cysts compressing the spinal cord are rare
      lesions. We retrospectively analyzed a series of patients harboring this entity
      with regard to clinical and radiological features, surgical management, and
      follow-up results. METHODS: In a retrospective study, we reviewed the medical
      charts, radiological investigations, and follow-up data of 11 women and 10 men
      (mean age, 43.6 yr) with intradural juxtamedullary spinal cysts, which were
      consecutively treated microsurgically at our institutions between January 1995
      and January 2003. All lesions were approached via a laminectomy, hemilaminectomy,
      or laminoplasty at the corresponding vertebral levels and histopathologically
      verified. The patients were routinely scheduled for clinical follow-up 2 and 6
      months after surgery. Baseline postoperative magnetic resonance imaging (MRI) was
      ordered 6 months after surgery. Thereafter, follow-up was performed at 1-year
      intervals, with neurological examination and MRI. RESULTS: According to
      presenting symptomatology, two main patient groups could be differentiated: one
      group with a myelopathic syndrome (10 patients) and another group with a
      predominant radicular pain syndrome (8 patients). Histopathological examination
      revealed 16 arachnoid cysts, 4 neuroepithelial cysts, and 1 cervical nerve root
      cyst. Most arachnoid cysts (12 cases) were located on the dorsal aspect of the
      thoracic spinal cord. The mean craniocaudal extension of these cysts was 3.7
      vertebral levels, and complete resection was performed. In four patients, the
      arachnoid cyst was situated ventral to the spinal cord and involved up to 17
      vertebral levels. These patients had a history of major spinal trauma, and the
      cyst was generously fenestrated at its greatest circumference as depicted on
      preoperative MRI scans. The four neuroepithelial cysts and the cervical nerve
      root cyst were located on the ventral or ventrolateral aspect of the spinal cord,
      and their maximum sagittal extension was two spinal vertebral levels. Symptoms in
      all but two patients demonstrated major improvement; in particular, radiating
      pain disappeared immediately after surgery. There was no cyst recurrence on MRI
      after a mean follow-up period of 3.2 years. CONCLUSION: Intradural cysts should
      be considered in the differential diagnosis of lesions causing myelopathy and/or
      a radicular pain syndrome. Microsurgical resection or generous fenestration in
      cysts with large craniocaudal extensions effectively ameliorated patients'
      symptomatology. A description of the first documented case of a surgically
      treated intradural cervical nerve root cyst is provided.

PMID- 15574217
TI  - Pallidal stimulation for dystonia.
AB  - OBJECTIVE: High-frequency deep brain stimulation (DBS) of the globus pallidus
      internus (GPi) is a new and promising treatment option for severe dystonia. Yet
      only few studies have been published to date regarding this treatment. We present
      the results of DBS of the GPi in 17 patients with severe dystonia of different
      causes. METHODS: In our study, we included 10 patients with primary generalized
      dystonia, six patients with secondary generalized dystonia, and one patient with
      a severe dystonic cervical tremor. In all patients, DBS electrodes were implanted
      bilaterally within the GPi. Mean follow-up time was 36 months (range, 12-66 mo).
      Preoperative and postoperative evaluations (at least annually) were performed
      using the Burk-Fahn-Marsden scale. RESULTS: The best improvement was achieved in
      patients with DYT1-positive dystonia. Patients with DYT1-negative generalized
      dystonia showed inhomogeneous results. There was no significant change in
      patients with tardive dystonia. One case of Hallervorden-Spatz disease improved
      dramatically within the first 2 years. The improvement in the cervical dystonic
      tremor was disappointing, however. Three years after DBS implantation, we found a
      secondary worsening of symptoms in one patient with a DYT1-positive dystonia and
      in the patient with Hallervorden-Spatz disease. CONCLUSION: DBS of the GPi is a
      new and promising treatment option for dystonia. Secondary worsening may limit
      this therapy.

PMID- 15574218
TI  - A call to define stereotactic radiosurgery.
AB  - Stereotactic radiosurgery is the single-session, precise delivery of a
      therapeutically effective radiation dose to an imaging-defined target. Conceived
      and developed during the past 5 decades, stereotactic radiosurgery has involved
      significant advances, which have improved patient outcomes and made it a critical
      component of modern neurosurgical practice and training. In this article, a short
      history of stereotactic surgery and radiosurgery are presented, and radiosurgery
      is contrasted to radiation therapy. Adherence to accepted, descriptive terms in
      defining stereotactic radiosurgery and radiation therapy permits a clear
      distinction among the results of the different radiation delivery techniques for
      patients, physicians, and other interested parties.

PMID- 15574219
TI  - Toward an expanded view of radiosurgery.
AB  - Radiosurgery and radiotherapy were originally distinguished on the basis of the
      manner in which they protected normal tissues from radiation injury. Radiosurgery
      does so by precise targeting of cross-fired radiation beams to abnormal tissue,
      with abrupt falloff of radiation doses to surrounding normal tissue. Radiotherapy
      was historically less concerned with targeting accuracy and anatomic precision;
      normal tissues were protected by dividing doses into multiple fractions separated
      by time to allow recovery of normal tissues. By this means, radiotherapy applied
      radiobiological principles to disrupt dividing cells selectively. Despite the
      development of computer-based, image-guided frameless technology that eliminates
      the necessity to perform radiosurgery in a single session, there are some who
      still insist that radiosurgery be distinguished from radiotherapy on the basis of
      whether treatment is delivered in a single session. Here, we propose that this
      definition of radiosurgery is needlessly restrictive and that staging or
      hypofractionation of radiosurgical treatment permits the limited application of
      radiobiological principles of radiotherapy to improve radiosurgical treatment. We
      therefore define radiosurgery as a procedure that involves the active
      participation of a surgeon and in which spatially accurate and highly conformal
      doses of radiation are targeted at well-defined structures with an ablative
      intent.

PMID- 15574220
TI  - New variants of malignant glioneuronal tumors: a clinicopathological study of 40
      cases.
AB  - OBJECTIVE: To demonstrate that malignant glioneuronal tumors comprise a large
      spectrum of neoplasms, without mature ganglion-like cells, that may
      histologically resemble any malignant glioma (World Health Organization Grade III
      or IV) but have a distinct biological behavior. METHODS: This series includes all
      tumors diagnosed as malignant glioneuronal tumors (MGNTs) in our routine practice
      during a 2-year period during which neurofilament protein (NFP) immunostaining
      was performed in any case of suspected malignant glioma with unusual clinical,
      radiographic, and/or histological features. Immunostaining using neuronal markers
      (NFP, NeuN, synaptophysin, and chromogranin) and glial fibrillary acidic protein
      was done on paraffin sections after antigen retrieval. The presence of NFP
      positive tumor cells, including those in mitosis, was used as a hallmark
      diagnostic criterion of MGNT. RESULTS: All tumors coexpressed glial fibrillary
      acidic protein and NFP. Other neuronal markers tested were inconstantly
      expressed. No recurrence was observed at the primary site in 36.4% of patients
      who underwent gross total resection. Twelve patients (33.3%) developed intra
      axial and/or systemic metastases, and 4 were free of disease at 39 to 184 months.
      Univariate analysis revealed that gross total surgical resection was the most
      important prognostic factor predicting survival (44 versus 15 mo; P < 0.0001),
      followed by a long duration of symptoms (>1 yr; P = 0.005), young age at symptom
      onset (children versus adults; P = 0.045), and absence of necrosis (P = 0.02).
      Gross total surgical resection (P = 0.001) and a long duration of symptoms
      (symptoms > 1 yr; P = 0.013) proved to be independent and statistically
      significant prognostic factors in the multivariate analysis. CONCLUSION: NFP
      immunostaining is required to identify MGNTs accurately. Their distinction from
      malignant gliomas is of paramount clinical importance, particularly for
      neurosurgeons, because gross total surgical resection may be curative in some
      cases. Finally, MGNTs may account for the long-term survival and/or occurrence of
      metastases demonstrated in a subset of malignant gliomas.

PMID- 15574221
TI  - Delayed intracranial delivery of a nitric oxide donor from a controlled-release
      polymer prevents experimental cerebral vasospasm in rabbits.
AB  - OBJECTIVE: Decreased local availability of nitric oxide (NO) may mediate chronic
      vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Previous reports have
      shown that early treatment with NO prevents vasospasm in animals. We evaluated
      the efficacy of controlled-release polymers that contain the NO donor
      diethylenetriamine (DETA-NO) for the delayed treatment of vasospasm in a rabbit
      model of SAH. METHODS: DETA-NO 20% (wt/wt) was incorporated into ethylene-vinyl
      acetate (EVAc) polymers. Animals (n = 52) were randomized to two experimental
      groups. In the first group (n = 32), animals received SAH and implantation of
      either 20% DETA-NO/EVAc polymer at a dose of 0.5 mg/kg of DETA-NO (n = 16) or
      empty EVAc polymer (n = 16). Polymers were implanted 24 (n = 16) or 48 hours (n =
      16) after SAH. In the second group (n = 20), animals received SAH and
      implantation of either 20% DETA-NO/EVAc polymer at a dose of 1.3 mg/kg (n = 10)
      or empty EVAc (n = 10). Polymers were implanted 24 (n = 10) or 48 hours (n = 10)
      after SAH. An additional group (n = 16) underwent either sham operation (n = 6)
      or SAH only (n = 10). Animals were killed 3 days after hemorrhage, and the
      basilar arteries were processed for morphometric measurements. Results were
      analyzed using Student's t test. RESULTS: Treatment with 20% DETA-NO/EVAc
      polymers at a dose of 1.3 mg/kg significantly increased basilar artery lumen
      patency when administered at 24 (97 +/- 6% versus 73 +/- 10%; P = 0.0396) or 48
      hours (94 +/- 6% versus 71 +/- 9%; P = 0.03) after SAH. Treatment with 20% DETA
      NO/EVAc polymers at a dose of 0.5 mg/kg administered 48 hours after SAH
      significantly increased lumen patency (82 +/- 8% versus 68 +/- 12%; P = 0.03); a
      dose of 0.5 mg/kg, 24 hours after SAH, did not reach statistical significance (74
      +/- 7% versus 65 +/- 9%; P = 0.16). The SAH-only group had a lumen patency of 67
      +/- 12%. CONCLUSION: Delayed treatment of SAH with controlled-release DETA-NO
      polymers prevented experimental posthemorrhagic vasospasm in the rabbit. This
      inhibition was dose-dependent. This further confirms the role of NO in the
      pathogenesis of vasospasm.

PMID- 15574222
TI  - Calcium alginate provides a high degree of embolization in aneurysm models: a
      specific comparison to coil packing.
AB  - OBJECTIVE: Although flexible, current coils do not fill intracranial aneurysms to
      a high degree, and questions remain regarding their thrombogenic capacity. We
      evaluated the usefulness of calcium alginate as an embolic material for
      endovascular embolization in aneurysm models. METHODS: We assessed three
      endovascular methods of instilling calcium alginate into 10-mm sidewall and 7-mm
      bifurcation glass aneurysm models using a balloon catheter to seal the aneurysm
      orifice: 1) instillation of alginate and subsequent instillation of the reactive
      component calcium chloride (CaCl(2)) via a single-lumen catheter, 2) simultaneous
      instillation of alginate and CaCl(2) via a side-by-side double-lumen catheter,
      and 3) instillation of alginate mixed with CaCl(2) delivered from a concentric
      tube microcatheter. A 13-mm sidewall silicon aneurysm model was used to measure
      and compare the volume of calcium alginate occupying the aneurysm models.
      RESULTS: Instillation Method 1 did not achieve optimal filling of the aneurysm
      with calcium alginate. The percentage volumes of calcium alginate occupying the
      aneurysm were 69.2 +/- 7.7% and 84.6 +/- 5.4% for instillation Methods 2 and 3,
      respectively. In Method 3, calcium alginate began gelation upon leaving the
      catheter, entered the aneurysms in a strand form, and gelled to a mass that
      filled the aneurysm while conforming to its inner contour. CONCLUSION: Calcium
      alginate fills aneurysm models to a significantly higher degree than published
      results of the space filled by coils. Instillation of calcium alginate,
      especially in strand form, may produce an embolization that better fills and
      conforms to the contour of aneurysms compared with coils.

PMID- 15574223
TI  - Silencing of monocarboxylate transporters via small interfering ribonucleic acid
      inhibits glycolysis and induces cell death in malignant glioma: an in vitro
      study.
AB  - OBJECTIVE: Dependence on glycolysis is a hallmark of malignant tumors. As a
      consequence, these tumors generate more lactate, which is effluxed from cells by
      monocarboxylate transporters (MCTs). We hypothesized that 1) MCT expression in
      malignant tumors may differ from normal tissue in quantity, isoform, or both; and
      2) silencing MCT expression would induce intracellular acidification, resulting
      in decreased proliferation and/or increased cell death. METHODS: We quantified
      expression of MCT isoforms in human glioblastoma multiforme and glioma-derived
      cells lines by Western blot analysis. MCTs that were abundant or specific to
      glioma then were targeted in the model U-87 MG glioma cell line via small
      interfering ribonucleic acid-mediated gene silencing and tested for inhibition of
      lactate efflux, intracellular pH changes, reduced proliferation, and/or induction
      of cell death. RESULTS: MCT 1 and 2 were the primary isoforms expressed in human
      glioblastoma multiforme and glioma-derived cell lines. In contrast, MCT 3 was the
      predominantly expressed isoform in normal brain. Small interfering ribonucleic
      acid specific for MCT 1 and 2 reduced expression of these isoforms in U-87 MG
      cells to barely detectable levels and reduced lactate efflux by 30% individually
      and 85% in combination, with a concomitant decrease of intracellular pH by 0.6
      units (a fourfold increase in intracellular H(+)). Prolonged silencing of both
      MCTs reduced viability by 75% individually and 92% in combination, as measured by
      both phenotypic and flow cytometric analyses. CONCLUSION: MCT targeting
      significantly reduced the viability of U-87 MG cells mediated by both apoptosis
      and necrosis. This indicates that the strategy may be a useful therapeutic avenue
      for treatment of patients with malignant glioma.

PMID- 15574224
TI  - Personal memories of the history of stereotactic neurosurgery.
AB  - This article summarizes the author's personal memories of the first 50 years of
      stereotactic neurosurgery. The author provides a short summary of his education
      and his introduction to stereotactic neurosurgery. Some great pioneers of the
      field who played an important role in his training, including John F. Gillingham,
      Jean Talairach, Guillaume Guiot, Edvard Kandel, Hirotaro Narabayashi, Irving
      Cooper, Henry Wycis, and Lars Leksell, are described in detail. The author then
      discusses his own work in the treatment of movement disorders, chronic pain,
      epilepsy, and intractable psychiatric disorders. For his contributions to the
      field, the author received the Spiegel-Wycis Medal of the World Society for
      Stereotactic and Functional Neurosurgery in 2001.

PMID- 15574225
TI  - Aggressive intramedullary melanotic schwannoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intramedullary melanotic schwannomas are very rare
      lesions; only four cases have been reported previously. We describe a patient
      with an intramedullary melanotic schwannoma that had a more aggressive course
      than those reported in the literature, and we review the theories regarding the
      cause of these lesions. CLINICAL PRESENTATION: A 35-year-old man presented with
      neck stiffness and paraesthesia extending down his right arm upon neck extension.
      A magnetic resonance imaging scan revealed an intramedullary lesion extending
      from C4 to C5. INTERVENTION: Gross total resection of the mass was performed, and
      pathological characteristics were consistent with a melanotic schwannoma. Two
      years after resection the tumor recurred, and the patient was treated with
      radiation therapy. The tumor progressed 2 years after radiotherapy, and at repeat
      resection, multiple pigmented foci were present on the surface of the spinal cord
      and dura consistent with metastatic seeding. CONCLUSION: In a patient with
      intramedullary melanotic schwannoma with an unusually aggressive course, careful
      follow-up may be essential.

PMID- 15574226
TI  - Multiple spinal cavernous malformations with atypical phenotype after prior
      irradiation: case report.
AB  - OBJECTIVE AND IMPORTANCE: This is the first reported case of histologically
      proven multiple spinal cavernous malformations (CMs) associated with previous
      irradiation. There are only two cases reported in the literature of solitary
      spinal CM after irradiation. In addition, the lesions in our patient had an
      atypical magnetic resonance imaging appearance mimicking intraspinal drop
      metastasis. CLINICAL PRESENTATION: A 33-year-old man had an incidental finding of
      multiple enhancing intraspinal lesions as revealed by magnetic resonance imaging
      during staging tests for hepatocellular carcinoma. He had a history of Wilms'
      tumor at a young age with irradiation to the abdomen and pelvis. His family
      history included a paternal cousin with multiple cerebral CMs. The diagnosis of
      spinal drop metastasis was made, and further intervention was undertaken for
      confirmation. INTERVENTION: The patient underwent a lumbar laminectomy with
      durotomy and excision of two of the lesions. Macroscopic analysis revealed
      mulberry-like appearance with nerve root involvement, and pathological analysis
      confirmed the diagnosis of CM. Genetic testing of the patient and his affected
      cousin was negative for the CCM1 gene. CONCLUSION: The occurrence of multiple
      spinal lesions in the context of known neoplasia indicates a diagnosis of
      metastasis. Spinal CMs were not suspected preoperatively because of the atypical
      appearance revealed by magnetic resonance imaging scans, with uniform contrast
      enhancement and absence of hemosiderin rim. This case report is discussed
      relative to previous literature regarding radiation-induced CMs and other known
      causes of the disease.

PMID- 15574227
TI  - Intramedullary cervical spine germinoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report an extremely rare case of primary
      intramedullary germinoma in the cervical spinal cord arising in an 18-year-old
      man who had not undergone previous surgery or irradiation. CLINICAL PRESENTATION:
      The patient had a 2-month history of intermittent neck pain and a 4-week history
      of bilateral hand paresthesias and weakness. A magnetic resonance imaging scan
      demonstrated a heterogeneous cervical spine lesion with marked contrast
      enhancement extending from C3 to C6. INTERVENTION: The patient underwent a
      cervical laminotomy with tumor resection, and pathological examination revealed
      the tumor to be a germinoma. He recovered well from the surgery with minimal
      neurological deficits. A postoperative magnetic resonance imaging scan of the
      brain and spinal cord did not show any other tumors. In addition, imaging studies
      of the mediastinum, testes, and the rest of the body also did not demonstrate any
      other tumors. The patient received local radiation as well as three courses of
      chemotherapy. CONCLUSION: To our knowledge, this is the first report of an
      intramedullary cervical spine germinoma with confirmed tissue diagnosis. Although
      extremely uncommon, the possibility of germinoma should be included in the
      differential diagnosis for primary intramedullary spinal cord tumors.

PMID- 15574228
TI  - Intrinsic arteriovenous malformation of the trigeminal nerve in a patient with
      trigeminal neuralgia: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intrinsic arteriovenous malformation (AVM) of the
      trigeminal nerve is extremely uncommon and may be associated with trigeminal
      neuralgia. CLINICAL PRESENTATION: A 55-year-old man experienced severe lightning
      pain in the second and third divisions of the left trigeminal nerve territory.
      Vertebral angiography demonstrated an AVM fed by the superior cerebellar artery.
      Magnetic resonance imaging with three-dimensional spoiled gradient recalled
      acquisition at steady state revealed an AVM intrinsic to the left trigeminal
      nerve and a small arterial loop causing compression at the root entry zone of the
      trigeminal nerve. INTERVENTION: Intraoperative inspection revealed an indentation
      of the root entry zone caused by a small arterial loop but not by the AVM. The
      offending artery was displaced to decompress the root entry zone using a
      prosthesis without resection of the AVM. The patient was relieved of the
      neuralgia immediately after surgery without further neurological deficit. He has
      been free of trigeminal neuralgia during a follow-up period of 2 years and is
      scheduled to undergo stereotactic radiosurgery for the treatment of the AVM.
      CONCLUSION: Intrinsic AVM of the trigeminal nerve may cause trigeminal neuralgia.
      However, as in the present case, a coexistent vascular lesion rather than the
      intrinsic AVM could be a cause of the neuralgia.

PMID- 15574229
TI  - Trigeminal neuralgia caused by a pontine abscess: case report.
AB  - OBJECTIVE AND IMPORTANCE: Various intracranial abnormalities, including
      infectious conditions, may manifest as trigeminal neuralgia. CLINICAL
      PRESENTATION: A 33-year-old man presented with a 15-day history of right-sided
      facial pain and numbness. Neurological examination revealed diminished corneal
      reflex and facial sensation in the right V(1)-V(2) distribution. Magnetic
      resonance imaging revealed a contrast-enhancing lesion centered at the right pons
      with extension of the enhancement to the sphenoid sinus. INTERVENTION: Broad
      spectrum antibiotics were administered for 6 weeks. This resulted in alleviation
      of symptoms and resolution of the lesion as revealed by repeat magnetic resonance
      imaging. CONCLUSION: Presentation of a pons abscess with trigeminal neuralgia is
      rare, and to the best of our knowledge has not been reported previously. The
      patient was treated successfully with antibiotics alone.

PMID- 15574230
TI  - Xanthogranuloma of the sciatic nerve: case report.
AB  - OBJECTIVE AND IMPORTANCE: Xanthogranulomas involving the central or peripheral
      nervous system are extraordinarily rare. None have been reported in the lower
      extremity. Here, we report and characterize the first case of xanthogranuloma of
      the sciatic nerve. CLINICAL PRESENTATION: A 58-year-old woman presented with
      poorly localized right back and groin pain. Magnetic resonance imaging studies
      revealed an enhancing lesion of the sciatic nerve in the right gluteal region.
      INTERVENTION: The sciatic nerve xanthogranuloma was resected without
      complication. CONCLUSION: Our report indicates that xanthogranuloma, although
      extremely rare, may occur throughout the nervous system. Our evaluation
      demonstrates that such lesions involving the peripheral nervous system have
      similar pathological characteristics to xanthogranulomas that more commonly occur
      in the skin.

PMID- 15574231
TI  - The pipes of pan.
AB  - The pipes of pan is the crowning achievement of Pablo Picasso's neoclassical
      period of the 1920s. This monumental canvas depicts a mythological Mediterranean
      scene in which two sculpted classical giants stare out, seemingly across the
      centuries, toward a distant and lost Arcadia. Picasso was influenced by Greco
      Roman art during his travels in Italy, and his neoclassical works typically
      portray massive, immobile, and pensive figures. Pan and his pipes are taken
      directly from Greek mythological lore by Picasso and placed directly into 20th
      century art. He frequently turned to various mythological figures throughout his
      metamorphosing periods. The Pipes of Pan was also influenced by the painter's
      infatuation with the beautiful American expatriate Sara Murphy, and the finished
      masterpiece represents a revision of a previously conceived neoclassical work.
      The Pipes of Pan now hangs in the Musee Picasso in Paris.

PMID- 15574232
TI  - Changing ethical standards in scientific publication.

PMID- 15574233
TI  - PEMF as treatment for delayed healing of foot and ankle arthrodesis.
AB  - BACKGROUND: Arthrodesis is the most common surgical treatment for foot and ankle
      arthritis. In adults, these procedures are associated with a 5% to 10% rate of
      nonunion. Pulsed electromagnetic field (PEMF) stimulation was approved by the
      Federal Drug Administration (FDA) for treatment of delayed unions after long-bone
      fractures and joint arthrodesis. The purpose of this study was to examine the
      results of PEMF treatment for delayed healing after foot and ankle arthrodesis.
      METHODS: Three hundred and thirty-four foot and ankle arthrodeses were done.
      Nineteen resulted in delayed unions that were treated with a protocol of
      immobilization, limited weightbearing, and PEMF stimulation for a median of 7
      (range 5 to 27) months. All patients were followed clinically and
      radiographically. RESULTS: The use of PEMF, immobilization, and limited
      weightbearing to treat delayed union after foot and ankle arthrodesis was
      successful in 5 of 19 (26%) patients. Of the other 14 patients with nonunions,
      nine had revision surgery with autogenous grafting, continued immobilization, and
      PEMF stimulation. Seven of these eventually healed at a median of 5.5 (range 2 to
      26) months and two did not heal. One patient had a below-knee amputation, and
      four refused further treatment. CONCLUSIONS: The protocol of PEMF,
      immobilization, and limited weightbearing had a relatively low success rate in
      this group of patients. We no longer use this protocol alone to treat delayed
      union after foot and ankle arthrodesis.

PMID- 15574234
TI  - Subtalar joint arthrodesis using a single lag screw.
AB  - BACKGROUND: This study tested the hypotheses that fusing the subtalar joint with
      a single lag screw from the posteroinferior calcaneus to the anterior talar neck
      is an effective technique and that factors affecting the time to fusion can be
      identified. METHODS: Between October, 1995, and July, 2002, the senior author
      (RAM) performed 101 isolated subtalar arthrodeses using a technique of single lag
      screw fixation from posteroinferior to anterosuperior across the posterior facet
      of the subtalar joint combined with the application of an autograft taken from
      the floor of the sinus tarsi and anterior process. The average patient age was 52
      (range 17 to 82) years. There were 52 women (53 arthrodeses) and 48 men (48
      arthrodeses). Eight of 101 (8%) arthrodeses were revisions. The indications
      included posttraumatic arthritis (45), posterior tibial tendon dysfunction (18),
      failed prior ankle joint fusion (14), idiopathic disorders (12), hindfoot
      coalition (7), rheumatoid arthritis (3), and Charcot-Marie-Tooth disease (2).
      Fifteen of 101 patients (15%) smoked an average of 0.9 +/- 0.5 pack of cigarettes
      per day. RESULTS: Two of 101 joints did not fuse, resulting in an overall fusion
      rate of 98%. The average time to fusion was 12.3 +/- 3.4 weeks. The presence of a
      prior ankle fusion significantly prolonged the time to fusion of the subtalar
      joint (11.9 +/- 2.3 vs. 14.9 +/- 7.0, p = .003). Other factors, including
      smoking, revision surgery, patient age, and patient sex, did not affect time to
      fusion. The fixation screw was removed in 13 of 101 (13%) joints at an average of
      8.8 +/- 0.5 months. CONCLUSIONS: Using a single 7.0-mm lag screw across the
      posterior facet of the subtalar joint results in fusion of the subtalar joint in
      98% of patients. A prior ankle arthrodesis delays the time to fusion of the
      subtalar joint by 3 weeks. This is a simple and reliable technique for achieving
      fusion of the subtalar joint.

PMID- 15574235
TI  - Calculation of the opening wedge for a low tibial osteotomy.
AB  - BACKGROUND: Medial opening wedge distal tibial osteotomy, a relatively new
      technique for treatment of intermediate ankle joint arthritis, is a technically
      demanding procedure that requires preoperative planning to determine the size of
      the wedge that will restore anatomic alignment of the joint surface. The purpose
      of this study was to facilitate the preoperative planning process for distal
      tibial osteotomy by determining angular correction obtained with various wedge
      heights. METHODS: Measurements of the distal tibia were taken from cadaver
      specimens to develop a database of average distal tibial widths. A distal tibial
      osteotomy was then done on the cadaver specimens with the placement of wooden
      block wedges of various heights at the osteotomy site. Preoperative and
      postoperative radiographic measurements of the joint surface angle were obtained
      on all specimens. The measured amount of angular change was compared to the
      mathematically predicted angular change using the formula tan theta = H/W.
      RESULTS: The mathematical model accurately predicted the amount of measured
      angular correction of the distal tibial articular surface. There was an
      approximate 2-degree angular change of the articular surface per millimeter of
      wedge height. As the tibial width increased, a smaller amount of angular
      correction per millimeter of wedge height was noted, and as wedge height
      increased with the same tibial width, less angular correction was obtained per
      millimeter of wedge height. CONCLUSION: With appropriate preoperative planning,
      an accurate prediction can be made as to the amount of ankle joint correction
      that should be obtained with surgery. The size of the wedge that will provide the
      desired amount of correction can be accurately determined preoperatively.

PMID- 15574236
TI  - Arthrodesis of the first metatarsophalangeal joint using a dorsal titanium
      contoured plate.
AB  - BACKGROUND: Arthrodesis of the first metatarsophalangeal joint (MTPJ) is used to
      treat a variety of foot pathologies. Numerous methods of internal fixation and
      bone end preparation have been reported. In an effort to bring together the best
      features of the various internal fixation devices, a low-profile contoured
      titanium plate (LPCT) using a compression screw was designed to be used with a
      ball-and-socket bone end preparation. A prospective study was carried out to
      determine the efficacy of this technique. METHODS: First MTPJ arthrodesis using
      an LPCT was done in 12 patients (10 women and two men) either as an isolated
      procedure (seven patients) or in conjunction with other forefoot procedures (five
      patients). The changes in the level of pain and activities of daily living were
      evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hallux
      score and the Short-Form 36 (SF-36) score. Time to bone union also was assessed.
      Mean followup was 18 months (+/-6 months). RESULTS: Statistically significant
      increases in the AOFAS hallux score and the SF-36 score were noted (p = .002 and
      .001, respectively). All radiographs showed bone union at 6 weeks and an
      appropriate degree of hallux dorsiflexion in relation to the first metatarsal (20
      to 25 degrees). CONCLUSION: The combination of the LPCT plate and a ball-and
      socket bone-end preparation has both operative and biomechanical advantages over
      other fixation techniques. This combination ensures that the anatomical length of
      the first ray is only minimally shortened and the angle of plantarflexion of the
      first metatarsal is maintained, resulting in preservation of medial column
      stability and a better functional result.

PMID- 15574237
TI  - Acceptability of ankle tourniquet use in midfoot and forefoot surgery: audit of
      1000 cases.
AB  - BACKGROUND: While use of a thigh tourniquet with general anesthesia is widely
      accepted, use of an ankle tourniquet in the awake patient is more controversial.
      In particular, it is not clear how long patients tolerate this device or what the
      consequences are of intraoperative tourniquet pain. METHOD: A prospective audit
      was done of 1000 patients undergoing midfoot and forefoot surgery using an ankle
      block. We examined the intraoperative problems associated with the use of an
      ankle tourniquet, particularly the role and consequences of intraoperative
      tourniquet pain. Risk factors for tourniquet pain were statistically examined,
      and patient acceptance was gauged through followup questions. RESULTS: With
      correct application and the option of sedation, 3.1% of patients complained of
      tourniquet pain. In 0.4% of patients tourniquet pain necessitated a conversion to
      general anesthesia. A significant association was found between tourniquet pain
      and both age and tourniquet time. We found that for patients younger than 70
      years of age, the tourniquet can be applied comfortably for up to 30 minutes in
      over 97%. For each 11 minutes beyond this, another 1% of patients reported
      tourniquet pain. However, patients 70 years or older had an average 3.5 times
      increase in tourniquet pain. In this age group the tourniquet can be applied
      comfortably for up to 30 min in 91%. For each 3.2 minutes beyond this, another 1%
      reported tourniquet pain. When questioned, 97.2% of our patients reported that
      they would have surgery again with an ankle tourniquet. CONCLUSIONS: Our audit
      shows that with correct application and the option of sedation the ankle
      tourniquet is well tolerated by most patients. However, clinicians need to be
      mindful that patients 70 years of age or older are at greater risk of tourniquet
      pain and that in all patients the risk of tourniquet pain gradually increases
      when application times exceed 30 min.

PMID- 15574238
TI  - Reconstruction of the chronically failed deltoid ligament: a new technique.
AB  - BACKGROUND: Chronic deltoid ligament insufficiency that results in valgus tilt of
      the talus within the ankle mortise (stage IV adult acquired flatfoot) represents
      a difficult and so far unsolved problem in foot and ankle surgery. If left
      uncorrected, the deltoid failure with malalignment predisposes to early ankle
      arthritis and the need for ankle arthrodesis or possibly ankle arthroplasty.
      METHODS: Five consecutive patients with deltoid ligament insufficiency resulting
      in a valgus tilt were treated with a deltoid reconstruction. Reconstruction of
      the deltoid ligament was done by passing a peroneus longus tendon graft through a
      bone tunnel in the talus from lateral to medial and then through a second tunnel
      from the tip of the medial malleolus to the lateral tibia. RESULTS: At a minimum
      2-year followup, all patients had correction of the talar tilt. One patient had 9
      degrees of valgus tilt remaining compared to 15 degrees preoperatively, and the
      procedure was considered a failure. The remaining four patients had correction of
      the valgus tilt to 4 degrees or less. CONCLUSION: Although not uniformly
      successful, deltoid ligament reconstruction using a tendon graft through
      appropriate bone tunnels can reconstruct the deltoid ligament and correct the
      valgus talar tilt. Successful results were achieved when combined with correction
      of flatfoot deformity, which is considered a necessary part of the procedure.

PMID- 15574239
TI  - Change in plantarflexion strength after complete detachment and reconstruction of
      the Achilles tendon.
AB  - BACKGROUND: Chronic insertional tendinitis of the Achilles tendon is an overuse
      injury seen with increasing frequency because of an aging population and an
      increased interest in sports. We evaluated the change in plantarflexion strength
      in patients after our surgical technique for chronic insertional Achilles
      tendinitis. METHODS: From our previous clinical series of detachment and
      reconstruction of the Achilles tendon for the treatment of insertional
      tendinitis, ten patients were evaluated with an average followup of 32.1 (range
      18 to 52) months. The average age was 65.7 years. We developed a mathematical
      model to predict the difference in plantarflexion strength between a
      reconstructed ankle and a healthy contralateral one. Isokinetic testing at 60
      degrees/second was performed, measuring plantarflexion peak torque, dorsiflexion
      peak torque, and total work. RESULTS: Our mathematical model predicted a decrease
      of 4% in plantarflexion torque after the surgery. Isokinetic testing found no
      significant differences in plantarflexion torque, dorsiflexion torque, or total
      work between the operated and nonoperated ankles. CONCLUSIONS: Complete
      detachment and reconstruction of the Achilles tendon do not decrease the working
      capacity of the gastrocsoleus muscle.

PMID- 15574240
TI  - Squamous cell carcinoma arising in chronic osteomyelitis in foot and ankle.
AB  - BACKGROUND: Squamous cell carcinoma arising from chronic osteomyelitis is
      uncommon, and although most occur in the lower extremities, occurrence in the
      foot and ankle is rare. METHODS: Between February, 1991, and May, 2003, we
      treated 14 patients (13 men and one woman) with squamous cell carcinomas arising
      in chronic osteomyelitis. The foot and ankle were affected in seven patients, and
      these comprised our study group. All seven patients were male, with a mean age of
      59.5 (range 54 to 63) years. An average of 27 (range 4 to 50) years passed
      between draining of the osteomyelitis and the diagnosis of the malignancy.
      Average followup was 68 (22 to 147) months. RESULTS: Six patients had amputations
      and one had limb salvage. Regional lymph node clearance was done in four
      patients, but metastasis occurred in only one patient who later died of the
      disease. CONCLUSION: In treating recalcitrant ulcers that have not responded to
      conventional modes of therapy, malignancy should be ruled out and a biopsy done.
      The treatment of choice for squamous cell carcinoma is amputation. Routine
      regional lymphadenectomy at the time of amputation seems unnecessary, but
      regional lymphadenopathy persisting for 3 months after amputation warrants
      surgical intervention.

PMID- 15574241
TI  - Synovial sarcoma presenting as posterior tibial tendon dysfunction: a report of
      two cases and review of the literature.

PMID- 15574242
TI  - Two cases of calcaneal osteosarcomas presenting as aneurysmal bone cysts.

PMID- 15574243
TI  - Pigmented villonodular synovitis about the ankle: a review of the literature and
      presentation in 10 athletic patients.
AB  - BACKGROUND: Pigmented villonodular synovitis (PVNS) is relatively uncommon. The
      disorder results in increased proliferation of synovium causing villous or
      nodular changes of synovial-lined joints, bursae and tendon sheaths. This study
      examines the occurrence of PVNS about the ankle and its association with trauma.
      METHODS: Ten patients over a 10-year period were identified as having PVNS of the
      ankle. The average age was 40.2 (range 27 to 62) years. There were four women and
      six men. Average followup was 4.5 (range 1 to 11) years from the initial surgery.
      Four patients had bone involvement. All patients who were athletically active
      before symptoms arose complained of persistent pain and swelling in the lateral
      ankle. Their initial clinical symptoms were indistinguishable from commonly
      associated pathologies with persistent lateral ankle pain (i.e. tenosynovitis,
      osteochondral defects, os trigonum injury, and tendon tears). All patients had
      magnetic resonance imaging (MRI) revealing PVNS, which is represented by low
      signal appearing masses on T1- and T2-weighted images. All patients'
      histopathology results revealed multinucleated giant cells and foam cells laden
      with hemosiderin deposits. All patients had synovectomy and tenosynovectomy.
      RESULTS: Eight patients were able to return to some sports (range 4 to 12
      months); two had continued pain, disability, and inability to return to sports
      because of recurrence. CONCLUSIONS: PVNS should be considered in athletically
      active patients with persistent lateral ankle pain and swelling, particularly if
      bone erosions are visible on plain radiographs.

PMID- 15574244
TI  - Frequency and effects of intratendinous and peritendinous calcifications after
      open Achilles tendon repair.
AB  - BACKGROUND: Although calcification of the Achilles tendon has been described by
      several authors, a detailed evaluation of its frequency and effects on clinical
      outcome has not been reported. The purposes of this work were to determine the
      frequency of calcifications in the Achilles tendon after open repair and their
      effects on clinical outcomes and to identify possible risk factors for
      postoperative calcification. METHODS: Thirty-six patients with open Achilles
      tendon repair were evaluated at an average followup of 19 months. Evaluation
      included a self-assessment questionnaire concerning treatment outcomes, clinical
      examination, and radiographic and ultrasonographic examinations. RESULTS: No
      patient had calcifications in the Achilles tendon area before surgery.
      Postoperatively, intratendinous or peritendinous calcifications, ranging in size
      from 3 mm to 37 mm, were found in 10 (28%) of the 36 patients. The development of
      calcifications was associated with chronic swelling, decreased range of motion of
      the ankle joint, and increase pain, especially with calcifications larger than 10
      mm. No association was found between the development of calcifications and the
      surgical technique, suture materials, time from injury to surgery, or
      postoperative management, and no risk factors could be identified. CONCLUSIONS:
      Calcifications of the Achilles tendon appear to be frequent after open tendon
      repair and to have a negative effect on clinical outcome.

PMID- 15574245
TI  - Bilateral deficits in postural control following lateral ankle sprain.
AB  - BACKGROUND: Although postural control deficits have been identified after lateral
      ankle sprains, objective and subjective comparisons of data before and after
      injury are limited. The purpose of this project was to prospectively assess and
      compare the changes in postural control and self-reported functional status in
      athletes who suffer acute lateral ankle sprains. We evaluated postural control
      and self-reported functional status before injury and at 1, 7, 14, 21, and 28
      days after acute lateral ankle sprain. METHODS: Postural control in single-limb
      stance and self-reported functional status were evaluated in 460 collegiate
      athletes during preseason examinations. Twenty-eight athletes suffered a lateral
      ankle sprain during the competitive season and participated in testing at 1, 7,
      14, 21, and 28 days after injury. RESULTS: Significant deficits in postural
      control were noted in both the injured and the uninjured ankles at 1 day after
      injury compared to the baseline measurements taken during the preseason
      examinations. Significant differences (p < .05) also were noted between the
      uninjured and injured ankles at 1, 7, and 21 days after injury. CONCLUSIONS:
      After lateral ankle sprain, postural control deficits occur in the injured and
      uninjured ankles, suggesting a central impairment in neuromuscular control.
      Changes in self-reported functional status followed a trend of deficit and
      improvement that was similar to that shown by the postural control data taken
      after injury, but the two measures did not strongly correlate.

PMID- 15574246
TI  - The effect of bone quality on the stability of ankle arthrodesis. A finite
      element study.
AB  - BACKGROUND: Despite uniform operating techniques, lack of fusion still occurs
      after ankle arthrodesis. Differences in the biological healing potential may be a
      factor but the mechanical performance of the arthrodesis construct because of
      varying bone quality also may be important. Internal compression techniques are
      preferred because of higher union rates, shorter fusion times, and fewer
      complications. A three-screw configuration has been shown to be more stable than
      a two-screw configuration, but it is not obvious when it should be used. METHODS:
      Three-dimensional finite element models of intact and flat-cut ankle arthrodeses
      were built, using two and three screws in different configurations. Poor bone
      quality was simulated by decreasing Young's modulus of the bone. The constructs
      were loaded in torsion and dorsiflexion, and micromotions at the fusion site were
      measured. RESULTS: Bone quality had a marked effect on the stability at the
      arthrodesis site. Inserting two screws at 30 degrees relative to the longitudinal
      axis of the tibia in an intact arthrodesis seemed the best option, especially as
      bone quality worsened. The addition of a third screw increased the stability at
      the arthrodesis site. CONCLUSIONS: Overall, intact joint surfaces and three-screw
      fixation, with the lateral and medial screws inserted produced the most stable
      arthrodesis constructs when bone quality was poor. CLINICAL RELEVANCE. Ankle
      arthrodeses are technically demanding because of the shape and small size of the
      talus. Preoperative planning is an absolute necessity to determine placement and
      number of screws. This study shows that poor bone quality decreases the stability
      of the arthrodesis constructs, suggesting that an attempt should be made to
      create the most stable three-screw configuration. Finite element models can be
      used as an effective preoperative tool for planning screw number and placement.

PMID- 15574247
TI  - [Pelvic ectasia in childhood. Do we know what it means and how it should be
      investigated?].

PMID- 15574248
TI  - [Neonatal pelvic ectasia: long-term outcome and association with ureterovesical
      anomalies].
AB  - OBJECTIVE: To analyze the outcome of neonatal pelvic ectasia (PE) and the
      association between this entity and vesicoureteral reflux and/or other urinary
      tract abnormalities. PATIENTS AND METHODS: We performed a retrospective study of
      255 children (205 boys, 50 girls) with an ultrasonographic diagnosis of PE in the
      first month of life. The initial ultrasonographic examination was indicated by
      urinary tract infection in 30 neonates, abnormalities in the prenatal
      ultrasonographic examination in 150 and by other reasons in 75. Pelvic ectasia
      was classified in four stages according to anteroposterior pelvic diameter: I < 1
      cm, II 1-1.5 cm, III 1.6-2 cm, and IV > 2 cm. RESULTS: Pelvic ectasia was
      bilateral in 153 children (60 %) and unilateral in 102 (left side in 81.4 % and
      right side in 18.6 %). Stage I was found in 75.49 %, stage II in 20.34 %, stage
      III in 3.9 % and stage IV in 0.24 %. The mean follow-up was 32.6 +/- 25.2 months.
      At the end of the first year, the results of renal ultrasound were normal in 70.2
      % of left-sided PE and in 55.9 % of right-sided PE, but 46 patients (18 %) showed
      worsening of PE between the first and second ultrasound scans. Voiding
      cystourethrography was performed in 79.6 % of the children and some abnormalities
      were found in 50 (24.6 %): urethral dilatations in two patients and
      vesicoureteral reflux in 48. No correlation was found between vesicoureteral
      reflux and the degree of ectasia (74 % had an anteroposterior diameter of < or =
      1 cm). Urinary tract infection was present in 24.3 % of the children and 13
      required surgery (eight pyeloplasties, four urethral reimplantations and two
      resections of type III urethral valves). CONCLUSIONS: Neonatal PE was more
      prevalent in boys (4:1) and was more frequently located on the left side in both
      sexes. Associated vesicourethral reflux was found in 23.64 % with no correlation
      between the degree of dilation and the presence or degree of reflux.
      Consequently, cystourethrography should be performed in any child with pelvic
      ectasia, regardless of stage, side or sex.

PMID- 15574249
TI  - [Prenatal hydronephrosis: incidence, management and final diagnoses in 2003].
AB  - BACKGROUND: Prenatal diagnosis of renal pyelectasis usually involves postnatal
      studies to determine whether treatment is necessary or not. OBJECTIVES: To
      determine the incidence of fetal pyelectasis in our environment, to review our
      postnatal management protocol, and to review definitive diagnoses. PATIENTS AND
      METHOD: We performed a retrospective review of newborns with a prenatal diagnosis
      of pyelectasis. The variables recorded included prenatal ultrasound examinations,
      gestational age, sex, anthropometric data, postnatal study (ultrasound,
      cystography, isotopic renogram) and indication for antibiotic prophylaxis.
      RESULTS: There were 21 newborns (nine boys and 12 girls). Pyelectasia were
      located in the right kidney in 10 patients, on the left in seven and were
      bilateral in four. Antibiotic prophylaxis was administered at birth in seven
      neonates. Postnatal ultrasound was performed at 17.19 +/- 12.7 days of life and
      revealed no abnormalities in seven patients, hydronephrosis grade I-II in nine,
      hydronephrosis grade III in three and suspected double excretion system in two.
      Cystourethrography and isotopic renogram were performed in six neonates. The
      definitive diagnoses in the 21 patients were: no abnormalities in 10, non
      complicated renal dilatation in seven, double excretion system in two,
      vesicoureteral reflux grade IV in one and pyeloureteral stenosis in one. None of
      these newborns had urinary tract infection. CONCLUSIONS: The incidence of
      prenatal pyelectasis in our hospital is 2 %. Most pyelectasia resolve
      spontaneously in the first year of life and invasive investigations are not
      required. Adequate monitoring of these children can avoid urinary tract
      infections and their sequelae.

PMID- 15574250
TI  - [Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Association
      with ocular abnormalities].
AB  - BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is
      an unusual disease that usually leads to end-stage renal failure. There is no
      specific treatment and, to a variable degree, patients with this disease present
      ocular abnormalities. The illness is due to a defect in the reabsorption of
      magnesium and calcium at the thick ascending limb of Henle because of a mutation
      of the PCLN-1 gene, which encodes a protein, paracellin-1, which intervenes in
      the reabsorption of both cations. OBJECTIVE: To review outcome and the incidence
      of ocular abnormalities in our patients and in cases described in Spain and to
      compare the incidence found with that in groups from other countries. METHOD:
      Retrospective study of a group of patients with familial hypomagnesemia with
      hypercalciuria and nephrocalcinosis diagnosed at a hospital. RESULTS: There were
      six girls and three boys with clinical symptoms of polyuria, polydipsia, and less
      frequently, urinary tract infections and lithiasis. All had hypomagnesemia,
      hypercalciuria and nephrocalcinosis. Five of the patients had renal failure at
      diagnosis and four underwent transplantation without recurrence. Eight patients
      had diverse ocular abnormalities. Eighty-one percent of Spanish patients had
      ocular abnormalities compared with 24 % of those from other countries. There was
      no evidence of successful medical treatment. CONCLUSIONS: Almost half of the
      patients presented chronic renal failure at diagnosis and most of the patients
      reached end-stage renal failure in the second or third decade of life. Normal
      glomerular filtration rate was found only in patients diagnosed at an early age.
      The most frequent extra-renal association in Spanish patients (81 %) corresponded
      to ocular abnormalities. Effective treatment consists of kidney transplantation
      that completely corrects the tubular disorder.

PMID- 15574251
TI  - [Acute renal failure in critically-ill children. A preliminary study].
AB  - OBJECTIVE: To analyze the characteristics of acute renal failure (ARF) in
      critically-ill children and develop a protocol for a multicenter study. METHODS:
      A prospective, descriptive study was performed in four pediatric intensive care
      units (PICU) over 5 months. Epidemiological, clinical and laboratory data from
      children aged between 7 days and 16 years with ARF were analyzed. Premature
      neonates were excluded. RESULTS: There were 16 episodes of ARF in 14 patients and
      62.5 % were male (mean 6 SD age: 50 +/- 49 months). The incidence of ARF was 2.5
      % of PICU patients. The most frequent primary diseases were nephro-urological (50
      %) and heart disease (31 %). The main risk factors for ARF were hypovolemia (44
      %) and hypotension (37 %). Six patients (37.5 %) developed ARF following surgery
      (cardiac surgery in four, kidney transplantation in one and urological surgery in
      one). Furosemide was used in 13 patients (as continuous perfusion in nine),
      inotropes in nine and renal replacement therapy in 12. Medical complications were
      found in 94 % and some organic dysfunction was found in 81 %. The length of stay
      in the PICU was 21 +/- 21 days. The probability of death according to the
      Pediatric Risk of Mortality was 14 +/- 8 %. Five patients died (36 % of the
      patients and 31.2 % of ARF episodes). CONCLUSIONS: The incidence of ARF in
      critically-ill children is low but remains a cause of high mortality and
      prolonged stay in the PICU. Mortality was caused not by renal failure but by
      multiple organ failure.

PMID- 15574252
TI  - [Acute leukemia in patients with Down syndrome].
AB  - BACKGROUND: Children with Down syndrome (DS) have a higher risk of acute leukemia
      than the remaining pediatric population. A favorable outcome of acute myeloid
      leukemia (AML) has recently been described in these patients whereas the
      prognosis of acute lymphoblastic leukemias (ALL) is similar to that in other
      children. The main cause of morbidity and mortality in children with Down
      syndrome are complications related to chemotherapy, leading to numerous
      modifications in treatment protocols. OBJECTIVES: To characterize acute leukemias
      in children with Down syndrome in our center and determine their clinical
      outcome. METHODS AND RESULTS: Between 1990 and 2002, 214 children were diagnosed
      with acute leukemia at the Nino Jesus Hospital (40 with AML and 174 with ALL). Of
      these, eight children (3.8 %) had Down syndrome. AML (2/40) represented 5 % of
      myeloid leukemias and ALL (6/174) represented 3.4 % of lymphoblastic leukemias.
      The most frequent complication was hematologic toxicity due to chemotherapy,
      causing a high incidence of infections: pneumonia (5/8) and bacteriemia (5/8). In
      all patients, these complications led to treatment interruption or dose
      reduction. Two children died from treatment-related toxicity. Of these, one with
      AML developed fulminant sepsis due to Candida infection and the other, diagnosed
      with high risk ALL, died from multiorgan failure after high doses of methotrexate
      and ARA-C. CONCLUSIONS: Patients with Down syndrome diagnosed with acute leukemia
      show a higher incidence of treatment-related complications, which affects their
      prognosis. Consequently, individualized treatment of these children in qualified
      units is essential.

PMID- 15574253
TI  - [Congresses of the Spanish Association of Pediatrics: bibliometric analysis as a
      springboard for debate].
AB  - BACKGROUND: Congresses are periodic meetings that are required to make known and
      discuss advances in the various fields of medicine. Bibliometric indicators are
      important tools used to determine the quality of scientific publications.
      However, this type of study is infrequently performed in free communications of
      congresses. MATERIAL AND METHODS: A bibliometric study of all the free
      communications published in the congresses of the Spanish Association of
      Pediatrics over 4 years, divided in two periods (1996-1997 and 2000-2001) (n =
      2677) was performed. Bibliometric indicators were classified into quantitative
      (productivity), qualitative (statistical accessibility) and scientific evidence.
      RESULTS: Quantitative indicators: There were 928 free communications in 1996, 681
      in 1997, 560 in 2000, and 508 in 2001. Eighty-eight percent were in poster format
      and 87 % were in structured format. There was a median of six authors per
      communication. The main subject areas were infectology, neonatology, hemato
      oncology, neurology and endocrinology. Ninety-five per cent of communications
      were signed by hospitals with a marked contribution by hospitals in Andalusia and
      Madrid. Qualitative indicators: Statistical accessibility < 2 in 86 % and > 7 in
      2.9 %. Scientific evidence indicators: The quality of scientific evidence was
      good in only 1 % and was average in 9 %, since 90 % of all the studies were
      descriptive (mainly clinical cases). Evidence-based methodological concepts were
      used in only 1.9 %. Compared with 1996-1997, in 2000-2001 there were fewer
      communications, more posters, and more structured communications, as well as
      greater statistical accessibility and better scientific evidence indicators, but
      these differences were not statistically significant. CONCLUSIONS: Bibliometric
      study of the congresses of the Spanish Association of Pediatrics is a good
      starting point to analyze the quality of pediatric meetings and discuss possible
      solutions: a rigorous scientific committee with quality criteria, more analytical
      and/or experimental studies and fewer descriptive studies (especially clinical
      cases); restricting the number of authors per communication, greater
      collaboration with epidemiologists and/or biostatisticians, and favoring
      structured communications would also improve quality.

PMID- 15574254
TI  - [Prevalence of mechanical ventilation in pediatric intensive care units in
      Spain].
AB  - OBJECTIVE: To study the prevalence and characteristics of mechanical ventilation
      in children admitted to Spanish pediatric intensive care units (PICU). MATERIAL
      AND METHODS: A prospective, multicenter, observational study was performed using
      a written questionnaire sent to the 46 PICUs in Spain. Clinical data and
      mechanical ventilation settings in patients undergoing mechanical ventilation on
      19th February 2002 were collected. RESULTS: Thirty-three PICUs participated in
      the study (27 had patients undergoing mechanical ventilation on the study day).
      The prevalence of mechanical ventilation was 86 patients (45.5 %). The mean age
      of patients undergoing mechanical ventilation was 36 months and the median was 8
      months. Sixty percent of the patients were boys. The main indications for
      mechanical ventilation were acute respiratory failure (46.5 %), chronic
      respiratory failure (10.4 %), coma (11.6 %) and postoperative status (10.5 %).
      Endotracheal tubes were used in 73.2 % and a tracheostomy tube was used in 23.2
      %. The most frequent mechanical ventilation modalities used were synchronized
      intermittent mandatory ventilation (SIMV) in 43 % and control or assisted-control
      ventilation in 36 %. In 30 % of the patients the duration of mechanical
      ventilation was longer than 1 month. From the initiation of mechanical
      ventilation to the study day, pneumothorax developed in 8.1 % of the patients,
      accidental extubation occurred in 10.5 % and ventilator-associated pneumonia
      developed in 17.4 %. CONCLUSIONS: A high percentage of children admitted to the
      PICU requires mechanical ventilation. The most frequent indication is respiratory
      failure. The most frequently used modality in children aged less than 1 month is
      pressure SIMV. In children older than 1 month volume-cycled or pressure-limited
      ventilation and volume-cycled SMIV are used in similar proportions. The
      prevalence of prolonged mechanical ventilation and the incidence of ventilator
      associated complications are very high.

PMID- 15574255
TI  - [Congenital xerocytosis].
AB  - Hereditary xerocytosis is a genetic disease inherited as an autosomal dominant
      trait and is a rare cause of hemolytic anemia. It is caused by abnormal
      erythrocyte membrane permeability: monovalent cation pump activity is increased
      and the Na/K pump cannot compensate for the K lost. As a consequence, xerocytes
      dehydrate, becoming rigid and sensitive to metabolic stress and oxidation.
      Morbility depends on the severity of the hemolytic anemia. Periodic episodes of
      jaundice are common during mild infections; most patients remain asymptomatic but
      experience mild-to-moderate hemolytic anemia, which is generally well
      compensated. The diagnostic clues are a markedly increased flow through the Na/K
      pump with a decrease in total intracellular cation content and subsequent red
      cell dehydration. Treatment is based on monitoring for eventual complications and
      careful observation during infections, which may worsen the anemia. Splenectomy
      is not useful and for some authors may even be contraindicated. The prognosis is
      generally very good. We report the case of a patient with episodes of hemolytic
      anemia during intercurrent infections and positive diagnostic tests for
      hereditary xerocytosis.

PMID- 15574256
TI  - [Transient neonatal myeloproliferative disorder in the absence of Down syndrome].
AB  - Transient neonatal leukemia or transient neonatal myeloproliferative disorder is
      commonly associated with Down syndrome. It usually resolves spontaneously in 4-5
      months. However, 25 % of patients will subsequently develop acute
      megakaryoblastic leukemia or myelodysplastic syndrome. It has seldom been
      described without constitutional anomalies and is even less frequent in twins. We
      present three phenotypically normal patients with this disorder. One of them was
      diagnosed because he presented blueberry muffin syndrome. Diagnosis was guided by
      pathological examination of the skin lesions. The other two patients were
      monochorionic triplets. Their bichorionic sister presented no hematological
      disorders. Constitutional chromosomal abnormalities were ruled out in all three
      patients. They received support treatment only without chemotherapy. The clinical
      course was favorable with disappearance of marrow and peripheral blastosis in 4-5
      months. Follow-up of 18 and 19 months has not revealed any hematological
      disorders. Caution must be exercised before initiating chemotherapy in these
      patients. We discuss the differential diagnosis with congenital leukemia and the
      prognostic and therapeutic implications that this entails.

PMID- 15574257
TI  - [Chronic multifocal osteomyelitis].
AB  - The cases of three female Guinean children are described. Bloods tests were
      nonspecific, showing a moderately high globular sedimentation rate. The patients
      received combined therapy with systemic antibiotic therapy (including local
      gentamicin administration in two of the three patients) and surgery. One patient
      returned to Guinea and was lost to follow-up. The second patient showed severe
      sequelae and the third patient had a favorable outcome. In recent years, the
      prevalence of chronic osteomyelitis in Africa has increased. Most patients have
      multiple bone involvement and multiple etiology. Blood cultures are negative in
      40 % of patients and severe radiologic abnormalities, most commonly fractures,
      are frequent. A successful therapeutic regimen must be based on antibiotic and
      surgical treatment.

PMID- 15574258
TI  - [Primary peritonitis in previously healthy children].
AB  - INTRODUCTION: Primary peritonitis occurs rarely in childhood, affecting mainly
      children with nephrosis or liver disease and only rarely occurring in previously
      healthy children. The aim of this case report is to describe the clinical
      features and natural course of primary peritonitis in six previously healthy
      children and to review the literature on the topic. MATERIAL AND METHOD: The
      clinical features and course of primary peritonitis in six previously healthy
      children are described. The diagnosis was made at laparotomy, which showed no
      intraabdominal findings, such as intestinal perforation. RESULTS: Presentation
      was acute and all the patients presented within 24 h of onset of symptoms. The
      most common presenting features were fever (100 %) and abdominal pain (100 %).
      Leucocytosis (> 15,000/mm3) was observed in four patients (66 %). Microorganisms
      were isolated from peritoneal fluid in four patients (Escherichia coli in two,
      Streptococcus pneumoniae in one and Gram-negative bacteria in one). Recovery was
      rapid and no postoperative complications were observed. CONCLUSION: Primary
      peritonitis in patients without underlying causes is clinically indistinguishable
      from acute appendicitis and diagnosis is usually made at surgery. The hallmarks
      of therapy are antibiotics and prompt exploratory laparotomy with appendectomy
      and the prognosis is good.

PMID- 15574259
TI  - [Ovarian granulosa cell tumors: an unusual cause of precocious thelarche].
AB  - Precocious thelarche usually results from a physiological process but can
      sometimes be the first sign of precocious pseudopuberty. Ovarian granulosa cell
      tumors are highly unusual in childhood, appearing as precocious puberty in most
      prepuberal patients. During adolescence these tumors may cause menstrual
      irregularities, virilization and abdominal pain. Their malignancy is low and
      surgical treatment is usually curative if the tumors are limited to the ovaries.
      More advanced stages require chemotherapy, are difficult to cure and produce high
      mortality. We present the case of a 16-month-old girl with a granulosa cell tumor
      who presented with progressive precocious thelarche over 1 month that was
      satisfactorily resolved after resective surgery. This case demonstrates that
      other causes of puberal development should be investigated when precocious
      thelarche with fast progression is observed, with special attention paid to
      tumoral disease in the differential diagnosis.

PMID- 15574260
TI  - [Complete triploidy 69,XXY].

PMID- 15574261
TI  - [Congenital hemangiopericytoma].

PMID- 15574262
TI  - [Congenital fibrosarcoma of the thoracic wall].

PMID- 15574263
TI  - [Oral sildenafil: a promising drug for persistent neonatal pulmonary
      hypertension].

PMID- 15574264
TI  - [Hepatomegaly and cutaneous hemangiomas].

PMID- 15574266
TI  - [Bronchial colonization in chronic obstructive pulmonary disease: what's hiding
      under the rug].

PMID- 15574267
TI  - [Community-acquired pneumonia among the elderly: differences between patients
      living at home and in nursing homes].
AB  - OBJECTIVE: The etiology, presentation, and prognosis of community-acquired
      pneumonia (CAP) among nursing home residents are believed to differ from those of
      other groups. However, few Spanish studies have confirmed those assumptions or
      studied regional differences in CAP etiology. PATIENTS AND METHODS: A prospective
      study which included all patients over 65 years of age admitted to our hospital
      with CAP was carried out over a period of 18 months (2002-2003). We examined
      clinical, analytical, and radiographic characteristics paying particular
      attention to functional status--using the Eastern Cooperative Oncology Group
      (ECOG) scale and Barthel and Karnofsky indices--and comorbidity. Two blood
      cultures, a Legionella antigen test in urine, and serology for atypical bacteria
      were used for the etiologic diagnosis; bacterial cultures of respiratory samples
      were also used in certain cases. RESULTS: Ninety-one patients, 25 of whom were
      nursing home residents, were enrolled. The nursing home residents were older than
      the other patients (mean [SD] age of 82 [4] compared with 73 [5]; P=.0001) and
      had greater comorbidity (P=.0001)--with a significantly greater presence of
      diabetes mellitus, cerebrovascular disease, congestive heart failure, and
      dementia. They also had a poorer functional status (ECOG, 2.09 [0.9] compared
      with 0.93 [1.1], P=.001; Barthel Index, 19 [33] compared with 77 [35], P=.001;
      Karnofsky In-dex, 51 [17] compared with 78 [23], P=.001). Regarding clinical
      characteristics, significant differences were found for respiratory rate (39 [11]
      compared with 27 [7] breaths/min; P=.001), blood pressure (69.5 [20] compared
      with 79.2 [18] mm Hg; P=.029), and temperature (36.6 [1.2] compared with 37.7
      [1.1] degrees C; P=.001). CAP patients from nursing homes presented a greater
      number of affected lobules in chest x-rays (P=.004), more hypoxemia, acidosis,
      anemia, hypoalbuminemia, and greater scores of urea and creatinine. Fine Scale
      scores were also greater (134 [26] compared with 95 [28]; P=.001) as was
      mortality (7/25 compared with 3/66; P=.005). Few patients had an etiologic
      diagnosis and no significant differences were observed between the groups. The
      variable that predicted mortality in elderly patients in this series, according
      to stepwise logistic regression, was urea (adjusted R2=0.452). CONCLUSIONS: In
      our sample population, nursing home residents were older, had greater
      comorbidity, and severe functional impairment. Under these circumstances the
      severity of CAP increases and becomes an important cause of mortality despite the
      fact that the etiologic agents do not appear to differ from those of the other
      patients.

PMID- 15574268
TI  - [Evolution of lung cancer in the North of the province of Castellon, Spain, 1993
      2002].
AB  - OBJECTIVE: To investigate the changes in lung cancer incidence, histological
      type, and survival in patients in the north of the province of Castellon, Spain,
      during a follow-up period of 10 years, and to compare the findings with other
      national and international studies. PATIENTS AND METHOD: All patients diagnosed
      with lung cancer between January 1, 1993 and December 31, 2002 were included in
      this prospective, observational study. Disease was confirmed by biopsy or
      suspected from clinical, radiological, and/or bronchoscopic findings. RESULTS: In
      the study period, 271 patients were diagnosed with lung cancer (239 men and 32
      women), with a mean (SD) age of 66.8 (11.8) years. The age-adjusted incidence
      rate standardized to the world population was 20.42 cases per 100,000 population.
      Smokers or ex-smokers comprised 88.1% of the study population, and 72.6% of
      patients were over 60 years old. Biopsy confirmation was obtained in 262 cases
      (96.7%). Squamous cell carcinoma predominated (46.5%) but the proportion of
      adenocarcinoma increased (23.6%). Surgery was possible in only 22% of the
      patients. Mean overall 5-year survival was 15.7 months. CONCLUSIONS: In the north
      of the province of Castellon, the incidence of lung cancer continues to increase
      in men but has decreased slightly in women. Squamous cell carcinoma is the most
      common type, but the incidence of adenocarcinoma has clearly increased. Overall,
      survival did not improve during the 10 years of follow up despite advances in
      treatment.

PMID- 15574269
TI  - [Predictors of success at 6-month follow-up for smokers treated at a smoking
      cessation clinic].
AB  - OBJECTIVE: To identify the predictors of successful outcome in a smoking
      cessation program at 6-month follow-up. MATERIAL AND METHODS: Cross-sectional
      descriptive study of a sample of smokers who attended a smoking cessation clinic
      for combined medical and cognitive-behavioral group therapy. The independent
      variables assessed included age, sex, level of education, nicotine dependence
      (Fagerstrom test), prior attempts to quit smoking, medication prescribed,
      compliance with group therapy regimen, and success at one week and 3 months.
      Success was defined as self-reported abstinence, confirmed by CO-oximetry (carbon
      monoxide <10 ppm). Odds ratios (with 95% confidence intervals) were calculated
      for the categorical variables and a test of statistical significance of
      differences between means was performed for quantitative variables. Univariate
      logistic regression analysis was performed and significant variables were entered
      into a multivariate logistic regression model. RESULTS: The study population
      comprised 248 individuals, 67.7% male and 32.3% female, with a mean (SD) age of
      43.1 (10.5) years. The mean score on the Fagerstrom test was 6.3 (2.1) points and
      84.7% of the individuals complied with the treatment regimen. Success rates were
      as follows: 77% at one week, 30.2% at 3 months, and 31.9% at 6 months. Three
      variables--success at 3 months, age, and nicotine dependence--were entered into
      the multivariate logistic regression model; the only variable predictive of
      successful smoking cessation at 6 months was success at 3 months. CONCLUSIONS:
      Individuals who fully comply with treatment and abstain from smoking during the
      first weeks are more likely to be successful at 6 months.

PMID- 15574270
TI  - [Archivos de Bronconeumologia: among the 3 Spanish medical journals with the
      highest national impact factors].
AB  - OBJECTIVE: Citation analysis elucidates patterns of information consumption
      within professional communities. The aim of this study was to analyze the
      citations of 87 Spanish medical journals by calculating their impact factors and
      immediacy indices for 2001, and to estimate the importance of Archivos de
      Bronconeumologia within the framework of Spanish medicine. MATERIAL AND METHOD:
      Eighty-seven Spanish medical journals were included. All were listed in the
      Spanish Medical Index (Indice Medico Espanol) and in at least one of the
      following databases: MEDLINE, BIOSIS, EMBASE, or Science Citation Index.
      References to articles from 1999 through 2001 in citable articles from 2001 were
      analyzed. Using the method of the Institute for Scientific Information, we
      calculated the national impact factor and immediacy index for each journal.
      RESULTS: The journals with the highest national impact factors were Revista
      Espanola de Quimioterapia (0.894), Medicina Clinica (0.89), and Archivos de
      Bronconeumologia (0.732). The self-citation percentage of Archivos de
      Bronconeumologia was 18.3% and the immediacy index was 0.033. CONCLUSIONS: The
      impact factor obtained by Archivos de Bronconeumologia confirms its importance in
      Spanish medicine and validates its inclusion as a source journal in Science
      Citation Index and Journal Citation Report.

PMID- 15574271
TI  - [Utility of bronchoalveolar lavage in immunocompromised children: diagnostic
      yield and complications].
AB  - OBJECTIVE: Immunocompromised children are at high risk for developing pneumonia
      due to opportunistic pathogens. The role of bronchoalveolar lavage (BAL) in the
      evaluation of such patients is still controversial. MATERIAL AND METHOD: We
      reviewed the hospital records of immunosuppressed patients with respiratory
      symptoms who had undergone BAL in the pediatric department of the Hospital
      Clinico de la Pontificia Universidad Catolica of Chile. RESULTS: Sixty-eight BAL
      were performed on 54 children (mean age: 7.5 years) receiving wide-spectrum
      antibiotic treatment. The most frequent respiratory signs and symptoms were fever
      (90%) and cough and respiratory distress (81%); 18% had neutropenia and 43%
      thrombocytopenia. A specific pathogen was identified in BAL samples for 25
      patients (37%). The pathogens isolated were bacteria in 21 cases, viruses in 6,
      Pneumocystis carinii in 5, fungi in 4, and Mycobacterium tuberculosis in one.
      Fourteen (19%) of the children who underwent BAL were on mechanical ventilation.
      Outcome was satisfactory in all cases. Twenty-one complications were recorded, 17
      of which were minor (mild hypoxemia or fever) and 4 major, requiring tracheal
      intubation. No deaths were recorded. CONCLUSIONS: Evaluation by fiberoptic
      bronchoscopy together with BAL proved to be a safe procedure with an adequate
      diagnostic yield that made it possible to determine the etiology of the pulmonary
      infiltrates seen in chest x-rays. Both positive and negative results of BAL were
      useful for treating the patients.

PMID- 15574272
TI  - [Analysis of publications on COPD in Archivos de Bronconeumologia 2 years after
      the designated COPD year].

PMID- 15574273
TI  - [Guidelines for the diagnosis, treatment, and follow-up of pulmonary embolism].

PMID- 15574274
TI  - [Diffuse pulmonary ossification associated with idiopathic pulmonary fibrosis].
AB  - Diffuse pulmonary ossification is a rare entity that presents with the formation
      of mature bone in the pulmonary parenchyma and is associated with diffuse and
      chronic lung disease, heart disease, or other system disorders. Diffuse pulmonary
      ossification is usually a postmortem finding by the pathologist. In the case we
      report, the diagnosis was established by open lung biopsy. The patient was a 79
      year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A
      chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed
      tomography revealed interstitial disease predominantly in the septum with
      multiple cavitations that tended to form honeycomb patterns. Pleural thickening,
      retraction of the parenchyma, and bilateral fibrosis were also visible. A
      clinical diagnosis of interstitial fibrosis was established and the patient s
      course was unfavorable. An open lung biopsy was performed. The lung tissue
      specimens revealed zones with collapsed alveoli and others with emphysema, some
      of which produced secretion and erythrocytic extravasation. Interstitial vascular
      congestion was apparent; bronchioles presented mononuclear and some
      polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of
      predominantly interstitial, multicentric foci of osseous trabeculae --some of
      which included adipose bone marrow. Diffuse pulmonary ossification is usually an
      incidental finding in autopsies of patients with a history of diffuse chronic
      pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse
      pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It
      is a marker of the chronicity and/or severity of the fibrosis.

PMID- 15574275
TI  - [Diffuse thoracic lymphangiomatosis: diagnosis and treatment].
AB  - Histologically, lymphangiomatosis is a rare type of benign neoplasm caused by
      abnormal development and proliferation of the lymphatic system. Thoracic
      lymphangiomatosis can present in a localized (lymphangioma) or diffuse form
      (lymphangiomatosis). In most cases the disease progresses to serious morbidity or
      even death. The treatment of choice for localized disease is usually surgery or,
      less frequently, local injection of sclerosing agents (streptococcus antigen OK
      432). However, in diffuse forms there is a gelatinous infiltrate without defined
      limits. In these cases the main treatment option is radiotherapy. We report 2
      cases of diffuse thoracic lymphangiomatosis with pulmonary infiltrate. In both
      cases radiotherapy in appropriate doses successfully eliminated pulmonary
      infiltrates, pleural effusion, dyspnea, and general discomfort. Surgery was
      needed to resolve complications of the disease and for diagnosis.

PMID- 15574276
TI  - [Employment prospects for young Spanish pneumologists in the Association of
      Pneumologists of the South (Neumosur)].

PMID- 15574277
TI  - [Mediastinitis and pleural empyema caused by Streptococcus constellatus].

PMID- 15574278
TI  - [Spontaneous hemothorax due to rupture of a pulmonary artery aneurysm in Rendu
      Osler-Weber syndrome].

PMID- 15574280
TI  - [Subhepatic abscess as a late complication of missed intraperitoneal gallstone
      after laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy is the treatment of choice in symptomatic
      cholelithiasis. Despite its many advantages over the conventional laparotomic
      approach, accidental perforation of the gallbladder with spilled stones and bile
      leakage is frequent during this procedure. Complications from missed gallstones
      are uncommon, although they can sometimes lead to severe consequences. Great
      effort must be made to achieve laparoscopic retrieval of all the gallstones
      missed into the peritoneal cavity and conversion to an open procedure should be
      used only in selected cases. We report a case of subhepatic abscess as a late
      complication of a missed gallstone during a previous laparoscopic
      cholecystectomy.

PMID- 15574279
TI  - [Azathioprine and mesalazine in the prevention of postsurgical recurrence of
      Crohn's disease: a retrospective study].
AB  - OBJECTIVES: Surgical resection is still a mainstay of the treatment of Crohn's
      disease (CD). However, recurrence is the rule. The aim of the present study was
      to evaluate CD recurrence in a series of patients who underwent surgical
      resection with subsequent treatment with azathioprine (AZA) or mesalazine (5-ASA)
      and to identify the factors associated with recurrence. METHODS: The medical
      records of patients with CD who underwent bowel resection during a 4-year period
      were reviewed. Only patients who received AZA or 5-ASA as prophylaxis for
      recurrence were included. RESULTS: Thirty-three patients treated with AZA and 16
      treated with 5-ASA were included. Endoscopic recurrence was found in 8.6% of the
      AZA group and in 87.5% of the 5-ASA group (p <0.001). Clinical recurrence
      occurred in 31.2% of patients in the 5-ASA group and in none in the AZA group
      (p=0.004). The accumulated probability of both clinical and endoscopic recurrence
      was significantly lower in the AZA group (p=0.0025 and p=0.005, respectively).
      Factors associated with a greater risk of endoscopic recurrence were termino
      terminal anastomosis and 5-ASA treatment. The only factor associated with
      clinical recurrence was 5-ASA treatment. CONCLUSION: AZA seems to be more
      effective than 5-ASA in the prevention of postsurgical endoscopic recurrence of
      CD. Prospective studies with long-term follow-up are required to establish the
      true utility of AZA in the prophylaxis of CD recurrence.

PMID- 15574281
TI  - [Clinical guidelines for the prevention of colorectal cancer].

PMID- 15574282
TI  - [Latin-American consensus on irritable bowel syndrome: algorithm].

PMID- 15574283
TI  - [Birt-Hogg-Dube syndrome associated with intestinal polyposis].

PMID- 15574284
TI  - [Hepatopulmonary syndrome: relationship with liver dysfunction and systemic
      hemodynamic disorder].
AB  - BACKGROUND AND OBJECTIVE: The hepatopulmonary syndrome (HPS) causes an increased
      alveolar to arterial gradient of oxygen and in advanced phases hypoxemia, as the
      result of pulmonary vasodilation. In liver cirrhosis, it has been demonstrated
      the existence of splachnic vasodilation and also in other vascular beds. Our main
      objectives were to know the hemodynamic status, the renal function and the
      condition of some humoral systems in patient diagnosed of HPS. PATIENTS AND
      METHOD: We studied consecutively 32 cirrhotic patients Divided in two groups, a
      group of 18 cirrhotic patients with normal gaseous exchange (NGE), and another
      group of 14 cirrhotic patients diagnosed of HPS by contrast-enhanced
      transthoracic echocardiography and/or lung and brain scintigraphy with 99Tc
      albumin macroaggregates. They were all in rest in bed, upon alcohol and tobacco
      abstinence and on a diet of 50 mEq of sodium. Cardiovascular drugs were all
      withheld during 4 days in order to reach steady state. RESULTS: Patients of the
      HPS group were characterized by a more advanced index of Child-Pugh and presence
      of clubbing and vascular spiders. They presented a greater degree of hypoxemia in
      a sitting position, greater hypocapnia and smaller transference factor values
      (TLCO). They also showed a hyperkinetic circulatory condition characterized by
      smaller arterial blood pressure, greater cardiac index, smaller vascular
      resistances and greater femoral flows, with smaller clearance of creatinine,
      elimination of urinary sodium, urinary volume/24 h and an increased plasmatic
      volume, accompanied with a greater activation of the renin-angiotensin
      aldosterone axis and a greater urinary elimination of nitrites and nitrates.
      CONCLUSIONS: The pulmonary vasodilation that explains the HPS is a constitutive
      part of the systemic vasodilation occurring in liver cirrhosis, and it is related
      to the degree of liver dysfunction as measured by the classification of Child
      Pugh. The greater activation of the renin-aldosterone system and the rise of the
      plasmatic volume express a highest grade of arterial underfilling caused by an
      increment in the nitric oxide production.

PMID- 15574285
TI  - [Cardiovascular hyperactivity in patients with family history of high blood
      pressure].
AB  - BACKGROUND AND OBJECTIVE: The association between family history of essential
      high blood pressure (FH of HBP) and the cardiovascular hyperactivity to the
      isometric exercise is not well known; that is why the aim of this study was to
      describe this relation and to determine whether it is independent of the presence
      of cardiovascular risk factors. PATIENTS AND METHOD: We carried out a
      correlational descriptive study with a sample of 1855 people of both sexes
      between 18 and 70 years of age. The cardiovascular hyperactivity, expression of
      the cardiovascular response to the activity of the sympathetic nervous system
      (SNS), was determined by means of the test of the sustained weight (TSW).
      Comparisons of the values of cardiovascular reactivity were developed between
      individuals with and without FH of HBP and a model of logistical regression. The
      level of statistical significance was 95%. RESULTS: The arterial blood pressure
      at the end of the TSW was higher in individuals with FH of HBP independently of
      the age group. The cardiovascular hyperactivity, measured by means of they
      systolic index of cardiovascular reactivity, was also significantly higher in
      subjects with FH of HBP. Finally, individuals with FH of HBP showed a higher risk
      (more than 5 times) of having cardiovascular hyperactivity (OR = 5.16; CI 95%,
      3.51-7.59), this association being independent of other cardiovascular factors of
      risk. CONCLUSIONS: The FH of HBP is independently related to the cardiovascular
      hyperactivity, to the isometric exercise, of other cardiovascular risks factors.
      These elements help explain the relationship between cardiovascular
      hyperactivity, the activity of SNS and essential high blood pressure, at least in
      an important group of people.

PMID- 15574286
TI  - [Lack of association between blood pressure variability and left ventricular
      hypertrophy in essential hypertension].
AB  - BACKGROUND AND OBJECTIVE: Blood pressure (BP) fluctuations may contribute to the
      development of target organ damage in essential hypertension. However, a possible
      relationship with left ventricular hypertrophy (LVH) is controversial. The aim of
      the present study was to analyze the association between BP variability, defined
      through different instrument measures, and LVH in a group of essential
      hypertensive patients. PATIENTS AND METHOD: Forty-three untreated hypertensive
      patients were studied. BP variability was evaluated by using both non-invasive,
      beat-to-beat finger 24-hour monitoring (Portapres) and discontinuous
      oscillometric ambulatory blood pressure monitoring (ABPM). All patients underwent
      echocardiography in order to detect the presence or absence of LVH. RESULTS:
      Thirty out of 43 patients studied (70%) exhibited LVH. Office [167.7 (19.5)
      versus 156.7 (14.9) mmHg; p = 0.032], 24-hour ambulatory [146.6 (15.7) versus
      131.9 (15.1) mmHg; p = 0.003] and 24-hour continuous finger [147.5 (21.3) versus
      135.7 (14.2) mmHg; p = 0.046] systolic BP were significantly higher in patients
      with LVH with respect to those without cardiac hypertrophy. No differences were
      observed in terms of nocturnal BP fall, ABPM 24-h standard deviation of BP or
      continuous finger BP variability estimates. CONCLUSION: Left ventricular
      hypertrophy is mainly correlated with the severity of systolic BP elevation, but
      not with BP variability, neither long-term nor short-term.

PMID- 15574287
TI  - [International registry (of clinical trials)].

PMID- 15574288
TI  - [Hepatopulmonary syndrome: an infrequent and unknown disease].

PMID- 15574289
TI  - [Clinical and histopathological improvement of psoriasis in patients with
      osteoarthritis treated with chondroitin sulfate: report of 3 cases].
AB  - BACKGROUND AND OBJECTIVE: After prescribing chrondroitin sulfate for the
      symptomatic treatment of osteoarthritis, it has been observed that some patients
      with concomitant psoriasis experience a marked improvement of skin lesions. We
      describe the clinical and histopathological results of the erythematous and
      desquamative plaques of three patients with osteoarthritis and psoriasis treated
      with chondroitin sulfate. PATIENTS AND METHOD: Three adult patients with
      bilateral knee osteoarthritis and long-standing psoriasis characterized by
      extensive erythematous, desquamative, and hyperkeratotic plaques, which were
      resistant to different treatment modalities, received 800 mg/day of chondroitin
      sulfate during two months. Skin biopsies were obtained before and after
      treatment. RESULTS: All three patients presented a marked clinical improvement in
      both pathologies. In addition to a decrease in the thickness of the epidermis
      (total epidermal thickness, maximal thickness from the basal layer to the
      beginning of the corneal layer, and maximal thickness of the corneal layer), a
      decrease in the number of keratinocytes in the proliferative phase, a decrease in
      the degree of psoriatic activity, and a substitution of parakeratotic
      keratinization by orthokeratotic keratinization were observed. CONCLUSIONS: The
      administration of chrondroitin sulfate resulted in a significant clinical and
      histological improvement of the psoriatic lesions. The confirmation of these
      preliminary results in future clinical trials could represent an important
      advance in the therapeutic armamentarium of patients with psoriasis given the
      excellent safety profile of this drug.

PMID- 15574290
TI  - [Multiple sclerosis: diagnosis and treatment].

PMID- 15574291
TI  - [Secreted phospholipases A2 (sPLA2): friends or foes? Are they actors in
      antibacterial and anti-HIV resistance?].
AB  - In this paper the authors update on the deletereous or beneficial roles of human
      and animal secretory phospholipases A2 (sPLA2). Although human sPLA2-IIA
      (inflammatory) was initially thought as a foe because its pathogenic implication
      in sepsis, multiorganic failure or other related syndromes, recent data indicates
      its role in in the antiinfectious host resistance. Thus, sPLA2-IIA exhibits
      potent bactericidal activities against gram-negative and gram-positive (in this
      case, together with other endogenous inflammatory factors) bacteria.
      Surprisingly, human sPLA-IIA does not show in vitro anti-human immunodeficiency
      virus (HIV) activity, whilst several sPLA2-IA isolated from bee and serpent
      venons do it: this is the case for crotoxin, a sPLA2-IA isolated from the venon
      of Crotalus durissus terrificus (sPLA2-Cdt). The mechanism for the in vitro anti
      HIV activity of sPLA2-Cdt (inhibition of Gag p24) appears to be related to the
      ability of the drug to desestabilize ancorage (heparans) and fusion (cholesterol)
      receptors on HIV target cells.

PMID- 15574292
TI  - [Utilization of economic evaluations of health interventions: the palivizumab
      case].

PMID- 15574293
TI  - [Pulmonary arterial hypertension and Sjogren's syndrome: and uncommon
      association].

PMID- 15574294
TI  - [Visceral leishmaniasis in a patient treated with chemotherapy and radiotherapy
      for a cavum carcinoma].

PMID- 15574295
TI  - The effect of perceived spatial separation on informational masking of Chinese
      speech.
AB  - The effect of perceived spatial separation, induced by the precedence effect, on
      release from noise or speech masking was investigated. Listeners were asked to
      orally repeat Chinese nonsense sentences, which were spoken by a female talker
      and presented by both the left (-45 degrees) and right (+45 degrees)
      loudspeakers, when maskers, which were either speech-spectrum noise sounds or
      Chinese nonsense sentences spoken by two other female talkers, were presented by
      the same two loudspeakers. Delays between identical sounds presented over the two
      loudspeakers were used to control the perceived locations of the target (right
      only) and masker (right, center, or left). The results show that perceived 45
      degrees and 90 degrees separations of target speech from masking speech led to
      equivalently marked improvement in speech recognition, even though the degree of
      improvement was smaller than that reported in [J. Acoust. Soc. Am. 106 (1999)
      3578 (using English nonsense speech)]. When the masker was noise, however,
      perceived separation only marginally improved speech recognition. These results
      indicate that release from informational masking, due to perceived target/masker
      spatial separation induced by the precedence effect, also occurs for tonal
      Chinese speech. Compared to the 45 degrees perceived within-hemifield separation,
      the 90 degrees perceived cross-hemifield separation does not produce further
      unmasking.

PMID- 15574296
TI  - Mutation of the POU-domain gene Brn4/Pou3f4 affects middle-ear sound conduction
      in the mouse.
AB  - Mutagenesis of the POU-domain gene Brn4/Pou3f4 causes defects in the cochlear
      duct, semicircular canal, temporal bone and stapes footplate. The footplate
      defect suggested a middle-ear conductive component to the hearing loss associated
      with this mutation. This was examined by measuring velocity transfer functions at
      the umbo of wild type and knockout mice during sound stimulation of the tympanic
      membrane. When the median umbo velocity of test frequencies in the two groups
      were compared, the mid-range frequencies of the knockout mice showed a
      statistically reliable reduction in velocity (maximum of 13 dB) and high
      variability among animals. These results indicated that mutation of the POU
      domain gene, Brn4, changed middle-ear sound conduction when measured at the umbo.
      The origin of the abnormal velocity response was sought by puncturing a hole in
      the pars flaccida (PF), and subsequently, measuring movements at the umbo and the
      head of the long arm of the incus. This hole permitted us to measure velocity at
      the tip of the incus long arm, just above the incudostapedial joint. The
      comparison of umbo behavior in both groups with PF perforated showed a loss of
      sensitivity in the mid-range frequencies of the knockout animals. A comparison of
      incus velocity in the two groups also exhibited a velocity reduction in the mid
      range frequencies of the knockout animals. The reduction at the incus, however,
      was milder than observed at the umbo. The effect of the perforation in, and
      variability of, the knockout incus responses may have masked a more potent mid
      range frequency effect. Nevertheless, evaluation of the stapes and oval window in
      knockout mice showed variable pathology from ear to ear. The presence of this
      pathology, the mid-frequency loss in incus sensitivity and the variability in
      incus velocity among animals suggested that abnormal stapes behavior in Brn4
      deficient mice may determine the response of the ossicles, and thus account for
      the abnormal mid-frequency umbo behavior seen in knockout animals.

PMID- 15574297
TI  - Hearing loss associated with enlarged vestibular aqueduct and Mondini dysplasia
      is caused by splice-site mutation in the PDS gene.
AB  - Recessive mutations of PDS gene are the common causes of Pendred syndrome and non
      syndromic hearing loss associated with temporal bone abnormalities ranging from
      isolated enlargement of the vestibular aqueduct (EVA) to Mondini dysplasia. In
      this study we evaluate the relationship between EVA and Mondini dysplasia in 10
      prelingual deaf patients and PDS gene mutation. One of three mutations, IVS7-2A-
      >G, IVS16-6G-->A or IVS15+5G-->A, was identified in the PDS gene in each patient.
      In family studies of four probands with the IVS7-2A-->G mutation, we found that
      this mutation was inherited from the same mutant alleles of parental origin. The
      effect of IVS7-2A-->G mutation on PDS gene expression was determined by reverse
      transcription and polymerase chain reaction (RT-PCR). Sequencing of the RT-PCR
      products revealed that the PDS transcripts from the allele with IVS7-2A-->G
      mutation lose the entire exon 8, resulting in a joining of exons 7 and 9.
      Deletion of the exon 8 results in frameshift and premature termination of
      translation. Haplotype analysis showed a significant haplotype shared among the
      family members carrying IVS7-2A-->G mutation, suggesting that they may be derived
      from a common ancestor. Our results provide evidence that hearing loss with EVA
      and Mondini dysplasia may be caused by splice-site mutation in the PDS gene.

PMID- 15574298
TI  - The effect of different noise types on the speech and non-speech elicited
      mismatch negativity.
AB  - The effect of different types of real-life noise on the central auditory
      processing of speech and non-speech sounds was evaluated by the means of mismatch
      negativity and behavioral responses. Subjects (19-34 years old; 6 males, 4
      females) were presented, in separate conditions, with either speech or non-speech
      stimuli of approximately equal complexity in five background conditions: babble
      noise, industrial noise, traffic noise, wide band noise, and silent condition.
      Whereas there were no effects of stimuli or noise on the behavioral responses,
      the MMN results revealed that speech and non-speech sounds are processed
      differently both in silent and noisy conditions. Speech processing was more
      affected than non-speech processing in all noise conditions. Moreover, different
      noise types had a differential effect on the pre-attentive discrimination, as
      reflected in MMN, on speech and non-speech sounds. Babble and industrial noises
      dramatically reduced the MMN amplitudes for both stimulus types, while traffic
      noise affected only speech stimuli.

PMID- 15574299
TI  - High resolution scanning electron microscopy of the human organ of Corti. A study
      using freshly fixed surgical specimens.
AB  - Scanning electron microscopy on immediately fixed human cochleae obtained during
      surgery for life-threatening petro-clival meningioma showed excellently preserved
      morphology. We compared the morphological findings with those from transmission
      electron microscopic sections of well preserved human and animal tissue. The
      characteristics of neural innervation, the pathways of the nerves through the
      organ of Corti and the intimate relation of nerves to supporting cells along
      their route could be studied in detail. The lateral membranes of Hensen and
      Claudius cells were folded creating a surface enlargement. Marginal pillars
      extended the distal end of the tectorial membrane and correspond to the marginal
      net or "randfasernetz" described earlier. Stereocilia imprints at the
      undersurface of the tectorial membrane go as far as to the distal end of the
      marginal pillars. The presence of an irregularly distributed fourth row of outer
      hair cell, attached to the marginal pillars, raises questions about differences
      in the excitation of the last row of outer hair cells. The complex nature of many
      supporting cells, stria vascularis and Reissner's membrane, intracellular
      complexities as well as surface features are described. Supernumerary inner hair
      cells were observed and the different arrangement of outer spiral fibres in
      contrast to findings in animals and variations of nerve fibres within the organ
      of Corti between apex and base are discussed.

PMID- 15574300
TI  - Voltage-gated and background K+ channel subunits expressed by the bushy cells of
      the rat cochlear nucleus.
AB  - Bushy cells of the ventral cochlear nucleus produce a single, short latency
      action potential at the beginning of long depolarisations. In the present work an
      immunochemical survey was performed to detect the presence of K+ channel subunits
      which may contribute to the specific membrane properties of the bushy cells. The
      immunocytochemical experiments conducted on enzymatically isolated bushy cells
      indicated positive immunolabelling for several subunits known to be responsible
      for the genesis of rapidly inactivating K+ currents. Bushy cells showed strong
      expression of Kv3.4, 4.2 and 4.3 subunits, with the lack of Kv1.4 specific
      immunoreaction. The Kv3.4-specific immunoreaction had a specific, patchy
      appearance. Bushy cells also expressed various members of the Kv1 subunit family,
      most notably Kv1.1, 1.2, 1.3 and 1.6. Weak positivity could be observed for Kv3.2
      subunits. The positive immunolabelling for Kv3.4, Kv4.2 and Kv4.3 was confirmed
      in free-floating tissue slices. Voltage-clamp experiments performed on positively
      identified bushy cells in brain slices corroborated the presence and activity of
      Kv3.4 and Kv4.2/4.3 containing K+ channels. Bushy cell showed strong
      immunopositivity for TASK-1 channels too. The results presented in this work
      indicate that bushy cells possess several types of voltage-gated K+ channel
      subunits whose activity may contribute to the membrane properties and firing
      characteristics of these neurones.

PMID- 15574301
TI  - Cochlear maturation and otoacoustic emissions in preterm infants: a time
      frequency approach.
AB  - Click-evoked otoacoustic emissions (CEOAEs) from preterm infants were analyzed to
      characterize developmental changes of cochlear active mechanisms. Due to their
      strong time-varying properties, CEOAEs were studied with a time-frequency
      approach--the wavelet transform (WT). By means of the WT, CEOAEs were decomposed
      into 12 frequency bands, spanning the 0.25-6.25 kHz range. For each band, the
      root-mean-square (RMS) level and latency were studied as functions of both
      frequency and age. Because CEOAEs were averaged using the non-linear mode of
      acquisition, the developmental changes in observed in this study are related to
      the non-linear component (which is actually the most predominant component of the
      active cochlear response) of CEOAEs, the linear one being mostly canceled out by
      non-linear averaging. In our study, there was evidence that properties of CEOAE
      non-linear components are related to the post-conception age (PCA) in that the
      levels and latency of CEOAE frequency components changed until the age of about
      38 weeks post-conception, whereas after 38 weeks, CEOAE features were very
      similar to those of term newborns. In particular, the CEOAE levels increased and
      latency decreased with age. The observed changes in CEOAE properties seem to
      reveal a development of cochlear active mechanisms, although contributions from
      outer and middle ear development cannot be excluded. Also, in agreement with
      previous physiological and behavioral findings, our results revealed that the
      development of CEOAE properties was not the same for all the frequencies, being
      greater for frequencies 4 kHz, and resembled the development of the cochlear
      partition, which proceeds from base to apex.

PMID- 15574302
TI  - Objective evaluation of the effects of intravenous lidocaine on tinnitus.
AB  - OBJECTIVE: Tinnitus is one of the most common and distressing otological
      symptoms. Although numerous therapeutic modalities have been tried, there is no
      consensus regarding effective therapeutic agents up to now. The effects of
      lidocaine on tinnitus have been reported in literature using either subjective or
      audiologic tests. Nevertheless, the otoacoustic emissions (OAEs) have not been
      utilized to demonstrate lidocaine's effect on the cochlea in the English
      literature. The aim of this study was to evaluate the effect of lidocaine on
      tinnitus by considering the alterations with tinnitus, it induces on OAEs and
      subjective symptoms. METHODS: This study was performed in 30 patients with
      tinnitus. Twenty-eight of the patients had normal hearing and two of them
      evidenced mild sensorineural hearing loss. To determine the severity of tinnitus,
      the patients were required to fill out a tinnitus scoring scale before lidocaine
      infusion on the same day. Then, lidocaine was administered intravenously to each
      patient at a dose of 1.5 mg/kg body weight over a period of 30 min. Spontaneous
      otoacoustic emissions (SOAEs) and distortion product otoacoustic emissions
      (DPOAEs) were measured three times; namely before lidocaine injection, at 25 min
      after injection and on the next day. The severity of tinnitus was scored again 1
      d, 1 wk and 1 mo after lidocaine administration. RESULTS: Immediately after
      infusion, four patients (13.3%) declared total suppression of tinnitus, whereas
      three patients (10%) reported only partial relief in tinnitus subjectively. The
      patients, who had a subjective improved response (group 1) were compared with the
      patients, who had no response (group 2). Statistically significant changes
      (p<0.05) in DPOAE response/growth or input/output (I/O) functions were observed
      at 1, 2, 3, 4 and 6 kHz frequencies in lidocaine responders and at 1, 2, 3, 4 and
      5 kHz frequencies in no responders at different primary stimulus levels.
      Statistically significant changes (p<0.05) were seen at 2 kHz for 53 dB and at 3
      kHz for 62 dB SPL primaries in both groups. When the significant results of these
      two groups were compared with each other, differences were found insignificant.
      CONCLUSION: Systematic OAE measurements revealed that no changes occurred in SOAE
      and DPOAE levels in that alterations disappeared the next day. Subjective relief
      from tinnitus was stated in some of the patients and lasted for 4 wk at longest.

PMID- 15574303
TI  - Auditory cortical projections to the cochlear nucleus in guinea pigs.
AB  - We used anterograde tracing techniques to examine projections from auditory
      cortex to the cochlear nucleus in guinea pigs. Following injection of dextrans
      into the temporal cortex, labeled axons were present bilaterally in the cochlear
      nucleus. The distribution of boutons within the cochlear nucleus was similar on
      the two sides. The majority of boutons was usually located on the ipsilateral
      side. Most of the boutons were located in the granule cell areas, where many
      small boutons and a few larger, mossy-type endings were labeled. Additional
      small, labeled boutons were found in all layers of the dorsal cochlear nucleus,
      with the majority located in the fusiform cell layer. Labeled boutons were also
      present in the ventral cochlear nucleus, where they were located in the small
      cell cap as well as magnocellular parts of both posteroventral and anteroventral
      cochlear nucleus. Similar results were obtained with injections restricted to
      primary auditory cortex or to the dorsocaudal auditory field. The results
      illustrate direct cortical projections to the cochlear nucleus that are likely to
      modulate the activity in a number of ascending auditory pathways.

PMID- 15574304
TI  - Topographical anatomy of the guinea pig temporal bone.
AB  - Systematic anatomical description of the various structures of the temporal bone
      have been performed based on dissection of 16 guinea pigs (32 temporal bones). It
      has been found that besides two main air spaces in the middle ear, the tympanic
      bulla and dorsal bulla described in literature, there are also additional air
      cells in the mastoid process and facial nerve region in the temporal bone of a
      guinea pig. Moreover recesses were found in the walls of the tympanic bulla that
      formed almost completely separated partitions of tympanic cavity. The malleus
      head, the body of the incus and the superior and lateral semicircular canals as
      well as the facial nerve are easily accessible from the dorsal bulla. From the
      ventral tympanic bulla, one can access both windows and the cochlea. The
      semicircular canals are relatively large, the lateral canal is largest and the
      posterior the smallest. The cochlea has thin bony wall, and is composed of 3.5
      3.75 turns.

PMID- 15574305
TI  - Delayed-onset temporary auditory threshold shift following head blow in guinea
      pigs.
AB  - This study attempts to investigate the development of sensorineural hearing loss
      following a head blow without skull fracture in association with physiological
      and histopathologic changes in an experimental animal model. With the head in a
      freely movable position, albino guinea pigs were given a single blow to the
      occipital region by a head blow device. At 1, 7, and 14 days after the blow, the
      animals' auditory brainstem response (ABR) and cochlear microphonics (CM) were
      examined, and both the temporal bone and brain stem were observed by light and
      electron microscopy. The ABR threshold was unchanged at day 1, was significantly
      increased at day 7, and was fully recovered at day 14. The I-V and I-II interpeak
      latencies were significantly prolonged at days 1 and 7, and wave I latency was
      significantly prolonged at day 7 only. These latencies were recovered to normal
      limits at day 14. On the other hand, no significant change in CM versus the
      control group was observed at any point in the measurements. Histopathologically,
      no abnormal finding was seen at the light microscopic level. However, at the
      electron microscopic level, there were some injuries to the eighth nerve. At day
      1, the lamellar structure of the myelin sheath was irregular, and the periaxonal
      space was expanded; at day 7, the myelin sheath was disintegrated. At day 14,
      however, these changes were partially reversed. These results suggest that
      sensorineural hearing loss following a head blow in this model is attributed to
      dysfunction of the eighth nerve rather than to cochlear impairment.

PMID- 15574306
TI  - Netrin-1 as a guidance molecule in the postnatal rat cochlea.
AB  - During synaptogenesis a number of growth factors and peptides control the
      guidance of auditory neuron (spiral ganglion neuron, SGN) axons to their target
      cells. Furthermore, evidence suggests that these factors exert their actions at
      discrete times and sites during development. This study demonstrates that the
      guidance molecule netrin-1 is expressed in the early postnatal rat cochlea, but
      shows decreasing expression with increasing age. These results suggest that
      netrin-1 may be involved in guiding axonal growth from SGNs for the onset of
      innervation, but is not required for maintenance of synaptic connections.

PMID- 15574307
TI  - Human sound localization at near-threshold levels.
AB  - Physiological studies of spatial hearing show that the spatial receptive fields
      of cortical neurons typically are narrow at near-threshold levels, broadening at
      moderate levels. The apparent loss of neuronal spatial selectivity at increasing
      sound levels conflicts with the accurate performance of human subjects localizing
      at moderate sound levels. In the present study, human sound localization was
      evaluated across a wide range of sensation levels, extending down to the
      detection threshold. Listeners reported whether they heard each target sound and,
      if the target was audible, turned their heads to face the apparent source
      direction. Head orientation was tracked electromagnetically. At near-threshold
      levels, the lateral (left/right) components of responses were highly variable and
      slightly biased towards the midline, and front vertical components consistently
      exhibited a strong bias towards the horizontal plane. Stimulus levels were
      specified relative to the detection threshold for a front-positioned source, so
      low-level rear targets often were inaudible. As the sound level increased, first
      lateral and then vertical localization neared asymptotic levels. The improvement
      of localization over a range of increasing levels, in which neural spatial
      receptive fields presumably are broadening, indicates that sound localization
      does not depend on narrow spatial receptive fields of cortical neurons.

PMID- 15574308
TI  - Dissociation enzyme effects on the potassium currents of inner hair cells
      isolated from guinea-pig cochlea.
AB  - Tetraethylammonium (TEA)-sensitive potassium currents in the cochlear inner hair
      cells (IHCs) possess the kinetics of fast inactivation. Some enzymes using for
      IHCs dissociation affect these inactivation kinetics. IHCs were dissociated from
      guinea-pig cochlea by 1 mg/ml trypsin or 0.25 mg/ml protease VIII, and the
      properties of the K+ currents were compared using conventional whole-cell voltage
      clamp recordings. TEA-sensitive potassium currents showed fast inactivation
      kinetics in both trypsin-dissociated cells and protease VIII-dissociated cells.
      The time constant of the inactivation phase in trypsin-treated cells was similar
      to that in protease VIII-treated cells. However, the rate of inactivation
      (compared by the ratio between the steady-state current and initial peak current)
      in protease VIII-treated cells was larger than that in trypsin-treated cells. In
      protease VIII-dissociated cells, the time constant of recovery from inactivation
      elucidated by paired-pulse protocol was 3.5 ms. Papain is another enzyme that is
      sometimes used for dissociating IHCs, so effects of papain were observed.
      Extracellular papain application (8 unit/ml) demonstrated a slight increase of
      the outward potassium currents.

PMID- 15574310
TI  - COXIBs on TARGET.

PMID- 15574311
TI  - Hitting the target in medulloblastoma therapy.

PMID- 15574312
TI  - Skin stem cells.

PMID- 15574313
TI  - Products of yesteryear--blood mixture.

PMID- 15574314
TI  - Fight against cancer taking centre stage in Boston.

PMID- 15574315
TI  - Post-genome science highlights systems biology.

PMID- 15574316
TI  - Sulfotransferase structural biology and inhibitor discovery.
AB  - Sulfotransferases catalyze the transfer of a sulfuryl group from 3'
      phosphoadenosine 5'-phosphosulfate (PAPS) to proteins, carbohydrates and small
      molecules. The sulfotransferases comprise cytosolic and Golgi-resident enzymes;
      Golgi-resident enzymes represent fertile territory for identifying pharmaceutical
      targets. Structure-based sequence alignments indicate that the structural fold,
      and the PAPS-binding site, is conserved between the two classes. Initial efforts
      to identify sulfotransferase inhibitors by screening kinase inhibitor libraries
      yielded competitive inhibitors of PAPS with muM IC(50) values. Within particular
      classes of Golgi-resident sulfotransferases that show tight in vitro specificity,
      the substrate-binding site might be a suitable drug target, although
      sulfotransferases are generally assumed to be difficult to inhibit as a result of
      the expected size and chemical character of the substrate-binding site.

PMID- 15574317
TI  - The use of cell-penetrating peptides for drug delivery.
AB  - In the past decade, several peptides that can translocate cell membranes have
      been identified. Some of these peptides, which can be divided into different
      families, have short amino acid sequences (10-27 residues in length) and enter
      the cell by a receptor-independent mechanism. Furthermore, these peptides are
      capable of internalizing hydrophilic cargoes. Although the detailed mechanism by
      which these molecules enter cells is poorly understood, their ability to traverse
      the membrane into the cytoplasm has provided a new and powerful biological tool
      for transporting drugs across cell membranes.

PMID- 15574318
TI  - Improving the decision-making process in the structural modification of drug
      candidates: enhancing metabolic stability.
AB  - The activity-exposure-toxicity relationship, which can be described as "the rule
      of three", presents the single most difficult challenge in the design of drug
      candidates and their subsequent advancement to the development stage. ADME
      studies are widely used in drug discovery to optimize the balance of properties
      necessary to convert lead candidates into drugs that are safe and effective for
      humans. Metabolite characterization has become one of the key drivers of the drug
      discovery process, helping to optimize ADME properties and increase the success
      rate for drugs. Various strategies can influence drug design in the decision
      making process in the structural modification of drug candidates to reduce
      metabolic instability.

PMID- 15574323
TI  - Maurice Wilkins (1916-2004).

PMID- 15574324
TI  - Does common architecture reveal a viral lineage spanning all three domains of
      life?
AB  - Our discovery that the major coat protein of bacteriophage PRD1 resembles that of
      human adenovirus raised the unexpected possibility that viruses infecting
      bacteria could be related by evolution to those infecting animal hosts. We first
      review the development of this idea. We then describe how we have used structure
      based modeling to show that several other viruses with no detectable sequence
      similarity are likely to have coats constructed from similar proteins-the "double
      barrel trimer." There is evidence that the group includes a diversity of viruses
      infecting very different hosts in all three domains of life: Eukarya; Bacteria;
      and Archaea that diverged billions of years ago. The current classification of
      viruses obscures such similarities. We propose that the occurrence of a double
      barrel trimer coat protein in an icosahedral dsDNA virus with large facets,
      irrespective of its host, is a very strong indicator of its membership in a
      lineage of viruses with a common ancestor.

PMID- 15574325
TI  - DNA replication checkpoint prevents precocious chromosome segregation by
      regulating spindle behavior.
AB  - The DNA replication checkpoint maintains replication fork integrity and prevents
      chromosome segregation during replication stresses. Mec1 and Rad53 (human ATM/ATR
      and Chk2-like kinases, respectively) are critical effectors of this pathway in
      yeast. When treated with replication inhibitors, checkpoint-deficient mec1 or
      rad53 mutant fails to maintain replication fork integrity and proceeds to
      partition unreplicated chromosomes. We show that this unnatural chromosome
      segregation requires neither the onset of mitosis nor APC activation, cohesin
      cleavage, or biorientation of kinetochores. Instead, the checkpoint deficiency
      leads to deregulation of microtubule-associated proteins Cin8 and Stu2, which, in
      the absence of both chromosome cohesion and bipolar attachment of kinetochores to
      microtubules, induce untimely spindle elongation, causing premature chromosome
      separation. The checkpoint's ability to prevent nuclear division is abolished by
      combined deficiency of microtubule-destabilizing motor Kip3 and Mad2 functions.
      Thus, the DNA replication checkpoint prevents precocious chromosome segregation,
      not by inhibiting entry into mitosis as widely believed, but by directly
      regulating spindle dynamics.

PMID- 15574326
TI  - A biochemically defined system for mammalian nonhomologous DNA end joining.
AB  - Nonhomologous end joining (NHEJ) is a major pathway in multicellular eukaryotes
      for repairing double-strand DNA breaks (DSBs). Here, the NHEJ reactions have been
      reconstituted in vitro by using purified Ku, DNA-PK(cs), Artemis, and XRCC4:DNA
      ligase IV proteins to join incompatible ends to yield diverse junctions. Purified
      DNA polymerase (pol) X family members (pol mu, pol lambda, and TdT, but not pol
      beta) contribute to junctional additions in ways that are consistent with
      corresponding data from genetic knockout mice. The pol lambda and pol mu
      contributions require their BRCT domains and are both physically and functionally
      dependent on Ku. This indicates a specific biochemical function for Ku in NHEJ at
      incompatible DNA ends. The XRCC4:DNA ligase IV complex is able to ligate one
      strand that has only minimal base pairing with the antiparallel strand. This
      important aspect of the ligation leads to an iterative strand-processing model
      for the steps of NHEJ.

PMID- 15574327
TI  - A pathway of double-strand break rejoining dependent upon ATM, Artemis, and
      proteins locating to gamma-H2AX foci.
AB  - The hereditary disorder ataxia telangiectasia (A-T) is associated with striking
      cellular radiosensitivity that cannot be attributed to the characterized cell
      cycle checkpoint defects. By epistasis analysis, we show that ataxia
      telangiectasia mutated protein (ATM) and Artemis, the protein defective in
      patients with RS-SCID, function in a common double-strand break (DSB) repair
      pathway that also requires H2AX, 53BP1, Nbs1, Mre11, and DNA-PK. We show that
      radiation-induced Artemis hyperphosphorylation is ATM dependent. The DSB repair
      process requires Artemis nuclease activity and rejoins approximately 10% of
      radiation-induced DSBs. Our findings are consistent with a model in which ATM is
      required for Artemis-dependent processing of double-stranded ends with damaged
      termini. We demonstrate that Artemis is a downstream component of the ATM
      signaling pathway required uniquely for the DSB repair function but dispensable
      for ATM-dependent cell cycle checkpoint arrest. The significant radiosensitivity
      of Artemis-deficient cells demonstrates the importance of this component of DSB
      repair to survival.

PMID- 15574328
TI  - DNA damage-induced downregulation of Cdc25C is mediated by p53 via two
      independent mechanisms: one involves direct binding to the cdc25C promoter.
AB  - The Cdc25C phosphatase mediates cellular entry into mitosis. The cdc25C gene is a
      target for transcriptional downregulation by the tumor suppressor protein p53,
      and this repression can be shown to contribute to p53-dependent cell cycle
      arrest. Two independent mechanisms have been identified. One involves the direct
      binding of p53 to a site in the cdc25C promoter, and the second involves a
      CDE/CHR element. Both of these mediate p53-dependent repression at levels of p53
      comparable to those produced by DNA damage. Three CCAAT elements in the cdc25C
      promoter that were previously implicated in p53-dependent repression fail to do
      so at physiologically relevant levels of p53. Repression of Cdc25C by p53
      represents an additional mechanism for p53-dependent cell cycle arrest in
      response to DNA damage. Importantly, this is a clear demonstration of p53
      mediated transcriptional downregulation that is dependent on sequence-specific
      DNA binding by p53.

PMID- 15574329
TI  - The centrosomal protein CP190 is a component of the gypsy chromatin insulator.
AB  - Chromatin insulators, or boundary elements, affect promoter-enhancer interactions
      and buffer transgenes from position effects. The gypsy insulator of Drosophila is
      bound by a protein complex with two characterized components, the zinc finger
      protein Suppressor of Hairy-wing [Su(Hw)] and Mod(mdg4)2.2, which is one of the
      multiple spliced variants encoded by the modifier of mdg4 [mod(mdg4)] gene. A
      genetic screen for dominant enhancers of the mod(mdg4) phenotype identified the
      Centrosomal Protein 190 (CP190) as an essential constituent of the gypsy
      insulator. The function of the centrosome is not affected in CP190 mutants
      whereas gypsy insulator activity is impaired. CP190 associates physically with
      both Su(Hw) and Mod(mdg4)2.2 and colocalizes with both proteins on polytene
      chromosomes. CP190 does not interact directly with insulator sequences present in
      the gypsy retrotransposon but binds to a previously characterized endogenous
      insulator, and it is necessary for the formation of insulator bodies. The results
      suggest that endogenous gypsy insulators contain binding sites for CP190, which
      is essential for insulator function, and may or may not contain binding sites for
      Su(Hw) and Mod(mdg4)2.2.

PMID- 15574330
TI  - The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA
      export by tethering the helicase Dbp5 to the nuclear pore.
AB  - Nuclear export of mRNA in eukaryotic cells is mediated by soluble transport
      factors and components of the nuclear pore complex (NPC). The cytoplasmically
      oriented nuclear pore protein Nup159 plays a critical role in mRNA export through
      its conserved N-terminal domain (NTD). Here, we report the crystal structure of
      the Nup159 NTD, refined to 2.5 A. The structure reveals an unusually asymmetric
      seven-bladed beta-propeller that is structurally conserved throughout eukarya.
      Using structure-based conservation analysis, we have targeted specific surface
      residues for mutagenesis. Residue substitutions in a conserved loop of the NTD
      abolish in vitro binding to Dbp5, a DEAD box helicase required for mRNA export.
      In vivo, these mutations cause Dbp5 mislocalization and block mRNA export. These
      findings suggest that the Nup159 NTD functions in mRNA export as a binding
      platform, tethering shuttling Dbp5 molecules at the nuclear periphery and locally
      concentrating this mRNA remodeling factor at the cytoplasmic face of the NPC.

PMID- 15574331
TI  - Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during
      formation of a nuclear export complex.
AB  - CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich
      nuclear export signal (NES) by forming a cooperative ternary complex with the NES
      bearing substrate and the small GTPase Ran. We present a structural model of
      human CRM1 based on a combination of X-ray crystallography, homology modeling,
      and electron microscopy. The architecture of CRM1 resembles that of the import
      receptor transportin1, with 19 HEAT repeats and a large loop implicated in Ran
      binding. Residues critical for NES recognition are identified adjacent to the
      cysteine residue targeted by leptomycin B (LMB), a specific CRM1 inhibitor. We
      present evidence that a conformational change of the Ran binding loop accounts
      for the cooperativity of Ran- and substrate binding and for the selective
      enhancement of CRM1-mediated export by the cofactor RanBP3. Our findings indicate
      that a single architectural and mechanistic framework can explain the divergent
      effects of RanGTP on substrate binding by many import and export receptors.

PMID- 15574332
TI  - PHAX and CRM1 are required sequentially to transport U3 snoRNA to nucleoli.
AB  - To better understand intranuclear-targeting mechanisms, we have studied the
      transport of U3 snoRNA in human cells. Surprisingly, we found that PHAX, the
      snRNA export adaptor, is highly enriched in complexes containing m7G-capped U3
      precursors. In contrast, the export receptor CRM1 is predominantly bound to TMG
      capped U3 species. In agreement, PHAX does not export m7G-capped U3 precursors
      because their caps become hypermethylated in the nucleus. Inactivation of PHAX
      and CRM1 shows that U3 first requires PHAX to reach Cajal bodies, and then CRM1
      to be routed from there to nucleoli. Furthermore, PHAX also binds the precursors
      of U8 and U13 box C/D snoRNAs and telomerase RNA. PHAX was previously shown to
      discriminate between small versus large RNAs during export. Our data indicate
      that the role of PHAX in determining the identity of small RNAs extends to
      nonexported species, and this appears critical to promote their transport within
      the nucleus.

PMID- 15574333
TI  - Assembly and maturation of the U3 snoRNP in the nucleoplasm in a large dynamic
      multiprotein complex.
AB  - The assembly and maturation of box C/D snoRNPs, factors essential for ribosome
      biogenesis, occur in the nucleoplasm. To investigate this process, we have
      analyzed non-snoRNP factors associated with the nucleoplasmic human U3 snoRNA. We
      show that both the precursor and mature length nucleoplasmic U3 snoRNAs are
      present in larger multiprotein complexes that contain the core box C/D proteins
      as well as many non-snoRNP factors linked to snoRNP assembly (TIP48, TIP49,
      Nopp140), RNA processing (TGS1, La, LSm4, hRrp46), and subcellular localization
      (CRM1, PHAX). Using RNAi, we show that most of these factors are essential for
      box C/D snoRNA accumulation. Furthermore, we demonstrate that the core proteins
      undergo a restructuring event that stabilizes their binding to the snoRNA.
      Importantly, restructuring, which may be mediated by the putative remodeling
      factor TIP49, appears to be linked to nucleolar localization. We believe that the
      assembly complex coordinates snoRNA processing, snoRNP assembly, restructuring,
      and localization.

PMID- 15574334
TI  - Uniform binding of aminoacylated transfer RNAs to the ribosomal A and P sites.
AB  - The association and dissociation rate constants of eight different E. coli
      aminoacyl-tRNAs (aa-tRNAs) for E. coli ribosomes programmed with mRNAs of defined
      sequences were determined. Identical association and dissociation rate constants
      were observed for all eight aa-tRNAs in both the ribosomal A and P sites despite
      substantial differences in tRNA sequence, the type of esterified amino acid, and
      posttranscriptional modifications. These results indicate that the overall
      binding of all aa-tRNAs to the ribosome is uniform. However, when either the
      esterified amino acid or the tRNA modifications were removed, binding was no
      longer uniform. These results suggest that differences in tRNA sequences and tRNA
      modifications have evolved to offset differential thermodynamic contributions of
      the esterified amino acid and the codon-anticodon interaction so that ribosomal
      binding of all aa-tRNAs remains uniform.

PMID- 15574335
TI  - The first alpha helix of Bax plays a necessary role in its ligand-induced
      activation by the BH3-only proteins Bid and PUMA.
AB  - The mechanism by which some BH3-only proteins of the Bcl-2 family directly
      activate the "multidomain" proapoptotic member Bax is poorly characterized. We
      report that the first alpha helix (Halpha1) of Bax specifically interacts with
      the BH3 domains of Bid and PUMA but not with that of Bad. Inhibition of this
      interaction, by a peptide comprising Halpha1 or by a mutation in this helix,
      prevents ligand-induced activation of Bax by Bid, PUMA, or their BH3 peptides.
      Halpha1-mutated Bax, which can mediate death induced by Bad or its BH3 peptide,
      does not mediate that induced by Bid, PUMA, or their BH3 peptides. The response
      of Halpha1-mutated Bax to Bid can be restored by a compensating mutation in Bid
      BH3. Thus, a specific interaction between Bax Halpha1 and their BH3 domains
      allows Bid and PUMA to function as "death agonists" of Bax, whereas Bad recruits
      Bax activity through a distinct pathway.

PMID- 15574336
TI  - Hexokinase-mitochondria interaction mediated by Akt is required to inhibit
      apoptosis in the presence or absence of Bax and Bak.
AB  - The serine/threonine kinase Akt inhibits mitochondrial cytochrome c release and
      apoptosis induced by a variety of proapoptotic stimuli. The antiapoptotic
      activity of Akt is coupled, at least in part, to its effects on cellular
      metabolism. Here, we provide genetic evidence that Akt is required to maintain
      hexokinase association with mitochondria. Targeted disruption of this association
      impairs the ability of growth factors and Akt to inhibit cytochrome c release and
      apoptosis. Targeted disruption of mitochondria-hexokinase (HK) interaction or
      exposure to proapoptotic stimuli that promote rapid dissociation of hexokinase
      from mitochondria potently induce cytochrome c release and apoptosis, even in the
      absence of Bax and Bak. These effects are inhibited by activated Akt, but not by
      Bcl-2, implying that changes in outer mitochondrial membrane (OMM) permeability
      leading to apoptosis can occur in the absence of Bax and Bak and that Akt
      inhibits these changes through maintenance of hexokinase association with
      mitochondria.

PMID- 15574337
TI  - Transcriptional regulation of AKT activation by E2F.
AB  - The pRB-E2F pathway is a downstream target of mitogenic signaling pathways. The
      E2F family of transcription factors has a pivotal role in regulating cell
      proliferation since it controls the timely expression of many genes that are
      required for cell cycle progression. Moreover, at least one member of this
      family, E2F1, can mediate apoptotic cell death. We show here that E2F also
      modulates the activity of a major signal transduction pathway: we demonstrate
      that E2F upregulates AKT activity through a transcription-dependent mechanism. We
      identify the adaptor protein Grb2 associated binder 2 (Gab2) as a direct E2F
      target gene and an essential effector of E2F-dependent AKT activation. AKT
      activation was shown to inhibit E2F1induced apoptosis. Therefore, our results
      suggest the existence of a negative feedback loop involving E2F and AKT.

PMID- 15574338
TI  - N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1).
AB  - Expression of the CDK inhibitor p21(Cip1) is tightly regulated by signals that
      control cell division. p21 is an unstable protein that is degraded by the
      proteasome; however, the pathway that leads to proteasomal degradation of p21 has
      proven to be enigmatic. An important issue is whether proteasomal degradation of
      p21 occurs independently of ubiquitylation or, alternatively, whether
      ubiquitylation on its N terminus is crucial. We resolve this uncertainty by
      showing that endogenous cellular p21 is completely acetylated at its amino
      terminus and is therefore not a substrate for N-ubiquitylation. We further show
      that inactivation of essential components of the ubiquitylation machinery does
      not directly impact endogenous p21 degradation. Our results underscore the
      importance of N-acetylation in restricting N-ubiquitylation and show, in
      particular, that ubiquitylation of endogenous p21 either at internal lysines or
      on the N terminus is unlikely to control its degradation by the proteasome.

PMID- 15574343
TI  - Poly (O-aminobenzoic acid) modified glassy carbon electrode for electrochemical
      detection of dopamine in the presence of ascorbic acid.
AB  - O-aminobenzoic acid (o-ABA) film is deposited on glassy carbon electrode (GCE) by
      electropolymerization in pH 7.0 phosphate buffer solution (PBS). The polymeric
      film shows an excellent electrocatalytical activity on the oxidation of dopamine
      (DA). Difference pulse voltammetry (DPV) was performed to determine DA in an
      excess of ascorbic acid (AA). The oxidation peak potentials of DA and AA recorded
      are 144 mV and -52 mV, respectively. In pH 7.0 PBS, the anodic peak current of DA
      increases linearly over two concentration intervals, viz., 1.0x10(-7)-1.0x10(-5)
      mol L(-1) and 1.0x10(-5) - 2.0x10(-4) mol L(-1), with correlation coefficient,
      0.9966 and 0.9960, respectively. The relative standard deviation of 10 successive
      scans is 2.8 % for 1.0x10(-6) mol L(-1) DA and the recovery is 96 % - 101 %. The
      interference of AA and DOPAC with the determination of DA could be eliminated
      because of the very distinct attracting interaction between DA cations and the
      negatively poly (o-ABA) film in pH 7.0 PBS. The proposed method exhibits good
      recovery and reproducibility.

PMID- 15574344
TI  - Alpha-enolase plasminogen receptor in myogenesis.
AB  - Plasmin is a potent extracellular protease specialized in the degradation of
      fibrin (fibrinolysis). Active plasmin is generated by proteolytic activation of
      the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and
      tissue-type plasminogen activator (tPA). Alpha-enolase, although traditionally
      considered a glycolytic enzyme, constitutes a receptor for plasminogen on several
      cell types, serving to localize and promote plasminogen activation
      pericellularly. Localization of plasmin activity on the cell surface plays a
      critical role in fibrinolysis and in physiopathological processes involving
      extracellular matrix remodelling. Previous studies have unambiguously
      demonstrated that uPA-dependent plasmin generation is necessary for myogenesis in
      vitro and for muscle regeneration in vivo. However, the implication of alpha
      enolase plasminogen receptor in myogenesis had never been investigated. This
      review focuses on the recently reported expression and function of alpha-enolase
      plasminogen receptor during myogenesis. Skeletal myoblasts express alpha-enolase
      plasminogen receptor, being its expression greatly induced during the
      differentiation process in vitro. MAb 11G1, a monoclonal antibody against anti
      alpha-enolase plasminogen receptor, that inhibits plasmin generation, was able to
      fully abrogate myoblast fusion and differentiation. Moreover, both plasmin
      activity and alpha-enolase plasminogen receptor expression were significantly
      augmented in injury-induced regenerating muscle of wild type mice and in the
      dystrophic muscle of mdx mice, an animal model of Duchenne muscular dystrophy
      (DMD). Altogether, these results indicate that the plasminogen activation (PA)
      system is an important component of skeletal myogenesis in vitro and in vivo. In
      particular, the expression of alpha-enolase plasminogen receptor may serve to
      concentrate and enhance plasmin generation on the cell surface of migratory
      myoblasts contributing to efficient muscle repair.

PMID- 15574345
TI  - Electrochemical biosensors for DNA analysis.
AB  - Over the past few years, progress in electrochemical biosensors for DNA analysis
      is outstanding. This article briefly reviewed the principals of such biosensors,
      followed by a selection of topics that are of particular current interest.
      Selectivity and sensitivity are the two major challenges in DNA analysis. The
      former can be accomplished using peptide nucleic acids as probes, or relying on
      the DNA-mediated electron transfer. Special emphasis has been given to the
      efforts for high sensitivity, involving combination with polymerase chain
      reaction techniques, enzyme-labeled methods, direct label-free detection and nano
      based techniques.

PMID- 15574346
TI  - Peroxynitrite activates glucose uptake in 3T3-L1 adipocytes through a PI3-K
      dependent mechanism.
AB  - Peroxynitrite, the product of the reaction between *NO and O2*-, is a strong
      oxidant and nitrating molecule, and it has been recently consideredas a component
      of some important signaling pathways. Herein, we report the effect of
      peroxynitrite on glucose uptake in 3T3-L1 adipocytes. Peroxynitrite stimulated
      glucose uptake and this effect was inhibited by citochalasin B, indicating the
      participation of facilitated GLUT transporters. Peroxynitrite-induced glucose
      uptake was not related to intracellular ATP, nor to external or internal calcium,
      but it was inhibited by the phosphatidylinositol 3-kinase (PI3-K) inhibitor,
      wortmannin. Additionally, we also found that peroxynitrite did not activate the
      insulin receptor nor the PI3-K downstream signaling protein kinase B (PKB/Akt).
      The dose-dependent inhibitory action of wortmannin suggests that peroxynitrite
      activates glucose transport without affecting GLUT transporters translocation.

PMID- 15574347
TI  - Citrullinated proteins in rheumatoid arthritis.
AB  - Citrullinated proteins that are produced by enzymatic deimination of arginine
      residues in proteins by peptidylarginine deiminases (PADIs) are of particular
      interest in the pathogenesis of rheumatoid arthritis (RA). First,
      peptidylarginine deiminase type 4 (PADI4) gene, which codes one of the PADI
      enzyme isotypes, has a genetic variant that increases susceptibility to RA. The
      RA-susceptible variant of PADI4 seems to increase the risk of RA by increasing
      its enzymatic activity. Second, this post-translational protein modification
      unfolds proteins by loss of a positive charge in arginine residues, with a
      subsequent change in antigenicity of the self-proteins. Third, these
      citrullinated proteins are recognized by anti-citrullinated peptide antibodies
      that are the most RA-specific autoantibodies. Finally, the expression of the PADI
      enzyme, citrullination of proteins, and production of anti-citrullinated protein
      antibodies occur in synovium. These data suggest that citrullination of proteins
      by PADI is related to alteration of antigenicity of peptides and very closely
      linked to pathogenesis of RA autoimmunity.

PMID- 15574348
TI  - Mechanical strain leads to condylar growth in adult rats.
AB  - Mechanical strain produced by forward mandibular positioning was found to enhance
      mandibular condylar growth in experimental animals and in patients. This study
      was designed to identify the changes in number and rate of the proliferating
      mesenchymal cells in mandibular condyles of adult rats and to correlate these
      changes to the expression of SOX9 and type II collagen under mechanical strain.
      Seventy-eight 120-day-old female Sprague-Dawley rats were randomly allotted to
      six groups, nine animals in each experimental group according to different time
      points. Cell kinetic studies for expression of PCNA were used to identify number
      and rate of proliferating mesenchymal cells. Immunostaining of SOX9 and in situ
      hybridization of Col2a1 gene were carried out. Results showed a significant
      increase in number of replicating mesenchymal cells and proliferation rate. The
      expression of SOX9 was enhanced and Col2a1 gene transcript was then activated.
      The proliferative layer became thicker on experimental day 21. The thickness of
      chondroblast layer and chondrocyte layer showed significant increase from
      experimental day 14 to day 30. In conclusion, mechanical strain produced by
      mandibular advancement in adult rats promotes the proliferation of mesenchymal
      cells. Under control of transcription factor SOX9, these mesenchymal cells are
      then committed to enter the chondrogenic route leading to condylar growth.

PMID- 15574349
TI  - Neovascularization and mandibular condylar bone remodeling in adult rats under
      mechanical strain.
AB  - The present study was designed to explore the relationship between
      neovascularization, hypertrophic cartilage and the microstructural properties of
      cancellous bone in adult rat's condyle in response to mechanical strain produced
      by mandibular advancement.Seventy-eight 120-day-old female Sprague-Dawley rats
      were randomly allotted to six groups, nine animals in each experimental group
      according to different time points. Mandibular advancement appliances were used
      to produce mechanical strain onto to the mandibular condyles of rats.
      Immunostaining of VEGF and type X collagen were carried out. Tartrate-Resistant
      Acid Phosphatase (TRAP) reaction was used to assess the activity of
      chondroclasts. Direct three-dimensional morphometric analysis was carried out
      with microcomputed tomography (Micro-CT) scanning to evaluate the properties of
      microstructure of cancellous bone in the mandibular condyles. Results showed that
      mechanical strain produced by mandibular advancement induced neovascularization
      in the posterior condyle marked by the increased expression of VEGF.
      Neovascularization coupled the remodeling of calcified cartilage as marked by the
      expression of type X collagen and new bone formation. The new bone formed in the
      adult condyle was characterized by thinner trabecular thickness, more trabecular
      number and increased trabecular space. In conclusion, mechanical strain produced
      by mandibular advancement induces neovascularization and osteogenesis leading to
      adaptive growth of condyle in adult rats.

PMID- 15574350
TI  - Characterization of membrane-associated substrates of Ca2+-dependent kinases in
      astrocytes.
AB  - Membrane-associated kinase substrates are likely transducers of extracellular
      signals elicited by neuroimmunomodulators and other signaling molecules. Whereas
      specific signal transduction pathways in astrocytes are being defined, the global
      view is lacking. We, therefore, characterized membrane-associated substrates of
      Ca2+-dependent kinases in primary astrocytes using 2-dimensional gel
      electrophoresis. Ten proteins were phosphorylated in vitro and characterized with
      respect to their relative molecular mass (in the range 10 kDa - 100 kDa),
      isoelectric point (range 4.2 - 9.0) and four conditions of phosphorylation. They
      varied broadly in their requirements for phosphorylation displaying distinct
      kinase preferences. Eight phosphoproteins were substrates of protease kinase C.
      Judging by abundance and intensity of phosphorylation, the principal PKC
      substrates were three acidic proteins associated with the plasma membrane. These
      results suggest that a relatively small number of membrane-associated proteins
      serve as transducers of signals mediated by Ca2+-dependent kinases and most of
      them are PKC substrates in astrocytes.

PMID- 15574351
TI  - Urinary iodine assays and ionophore based potentiometric iodide sensors.
AB  - Urinary Iodine has been widely regarded as a biochemical marker for control of
      iodine deficiency disorders. Based on the Sandell-Kolthoff reaction, most
      colorimetric assay methods for urinary iodine (UI) determination that have been
      developed require pretreatment of urine sample. The non-Sandell-Kolthoff methods
      for UI assay provide alternative approaches for UI assay requiring only simple
      pretreatment or even without pretreatment. The selective ionophore-based iodide
      electrodes are highly applicable to the UI assay for large population due to
      their high selectivity and sensitivity to iodide, amenability to automation and
      ease of miniaturization. In this report, different assay methods are reviewed,
      including pretreatment procedures for Sandell-Kolthoff UI analysis. Finally, a
      summary of the state-of-the-art of the iodide ionophore-based ISEs that are
      suitable for UI assays are addressed.

PMID- 15574352
TI  - Effect of enteric flora on inflammatory and angiogenic mechanisms in human
      intestinal microvascular endothelial cells.
AB  - The intestine is a highly vascularized organ, and the splanchnic microcirculation
      is now appreciated to play a key role in immune and inflammatory responses in the
      gut. Emerging evidence demonstrates that the enteric flora not only exerts an
      important effect on innate immunity and the mucosal immune system, but will also
      affect inflammatory and angiogenic mechanisms involving the gut microcirculation.
      In response to bacterial lipopolysaccharide, the intestinal microcirculation and
      its endothelial lining will undergo activation, which will contribute to cell
      adhesion molecule expression and the recruitment of leukocytes into the gut wall,
      an early and rate limiting step in the inflammatory process. This is balanced by
      the fact that human intestinal microvascular endothelial cells possess specific
      mechanisms of endotoxin tolerance, which will diminish inflammatory activation in
      response to repeated bacterial activation. Likewise, the process of angiogenesis,
      or new blood vessel growth is influenced by the presence of bacteria, which
      stimulate the release of angiogenic factors from innate immune mechanisms.
      Conversely, bacterial derived products of dietary carbohydrate fermentation, the
      short chain fatty acids, will decrease angiogenic mechanisms in human intestinal
      microvascular endothelial cells. In this review we summarize our present state of
      knowledge regarding the interplay between enteric flora and inflammatory and
      angiogenic activation of the intestinal microcirculation its microvascular
      endothelium.

PMID- 15574353
TI  - Biosensor commercialization strategy - a theoretical approach.
AB  - Biosensors are analytical devices, which use biological interactions to provide
      either qualitative or quantitative results. They are extensively employed in many
      fields such as clinical diagnosis and biomedicine, military applications, anti
      terrorism, farm, garden and veterinary analysis, process control, fermentation
      control and analysis, pharmaceutical and drug analysis, food and drink production
      and analysis, pollution control and monitoring, microbiology, bacterial and viral
      analysis, mining, and industrial and toxic gases. The biosensor market has
      significantly increased and will be mushrooming in the next decade. The total
      biosensor market is estimated to be 10.8 billion dollars by 2007. The emerging
      biosensor market presents both opportunities and obstacles to start-up biosensor
      entrepreneurs. The major challenge and threat for these entrepreneurs is how to
      predict the biosensor market and how to convert promising biosensor technology
      into commercialized biosensors. By adopting a simple commercialization strategy
      framework, we identify two key elements of biosensor commercialization strategy:
      excludability and complementary asset. We further divide biosensor
      commercialization environments into four distinct sub-environments: the
      Attacker's Advantage, Reputation-Based Idea Trading, Greenfield Competition and
      Ideas Factories. This paper explains how the interaction between these two key
      elements shapes biosensor commercialization strategy and biosensor industry
      dynamics. This paper also discusses alternative commercialization strategies for
      each specific commercialization environment and how to choose from these
      alternatives. The analysis of this study further provides a good reference for
      start-up biosensor entrepreneurs to formulate effective biosensor
      commercialization strategy.

PMID- 15574354
TI  - Hsp47 a novel collagen binding serpin chaperone, autoantigen and therapeutic
      target.
AB  - Hsp47 was originally discovered as a cell surface collagen binding protein,
      colligin, and was later shown to be an endoplasmic reticulum (ER) resident
      protein with collagen binding properties in chick fibroblasts. Hsp47 has been
      termed J6, gp46, CB48 and CBP2 in various other organisms and has been mapped to
      human chromosome 11q13.5 a known "hot spot" in a number of human cancers. Hsp47
      has been shown to be constitutively expressed with collagens; it is heat
      inducible and binds to both helical and non-helical forms of collagens. Hsp47
      binds closely to procollagen in the ER, but dissociates from it in the cis-Golgi
      to allow fibril formation. Hsp47 is over-expressed in many fibrotic diseases
      including: glomerulosclerosis, pulmonary fibrosis, liver cirrhosis, cicatricial
      pemphigoid, epidermolysis bullosa acquista and keloids. Hsp47 is associated with
      fibrosis following myocardial infarction and has been localized in
      artherosclerotic arteries. Among a number of rheumatoid conditions, Hsp47
      manifests properties of an autoantigen and in some cancers appears to be a
      biomarker. The unique properties of Hsp47 in modulating collagen production and
      its location to the cell membrane in many forms of cancer have designated Hsp47
      as a potential biomarker and/or therapeutic target for a number of conditions and
      diseases.

PMID- 15574355
TI  - Metabolism of vitamin D3 by cytochromes P450.
AB  - The vitamin D3 25-hydroxylase (CYP27A1), 25-hydroxyvitamin D3 1alpha-hydroxylase
      (CYP27B1) and 1alpha,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1) are members
      of the cytochrome P450 superfamily, and key enzymes of vitamin D3 metabolism.
      Using the heterologous expression in E. coli, enzymatic properties of the P450s
      were recently investigated in detail. Upon analyses of the metabolites of vitamin
      D3 by the reconstituted system, CYP27A1 surprisingly produced at least seven
      forms of minor metabolites including 1alpha,25(OH)2D3 in addition to the major
      metabolite 25(OH)D3. These results indicated that human CYP27A1 catalyzes
      multiple reactions involved in the vitamin D3 metabolism. In contrast, CYP27B1
      only catalyzes the hydroxylation at C-1alpha position of 25(OH)D3 and
      24R,25(OH)2D3. Enzymatic studies on substrate specificity of CYP27B1 suggest that
      the 1alpha-hydroxylase activity of CYP27B1 requires the presence of 25-hydroxyl
      group of vitamin D3 and is enhanced by 24-hydroxyl group while the presence of 23
      hydroxyl group greatly reduced the activity. Eight types of missense mutations in
      the CYP27B1 gene found in vitamin D-dependent rickets type I (VDDR-I) patients
      completely abolished the 1alpha-hydroxylase activity. A three-dimensional model
      of CYP27B1 structure simulated on the basis of the crystal structure of rabbit
      CYP2C5 supports the experimental data from mutagenesis study of CYP27B1 that the
      mutated amino acid residues may be involved in protein folding, heme-propionate
      binding or activation of molecular oxygen. CYP24A1 expressed in E. coli showed a
      remarkable metabolic processes of 25(OH)D3 and 1alpha,25(OH)2D3. Rat CYP24A1
      catalyzed six sequential monooxygenation reactions that convert 1alpha,25(OH)2D3
      into calcitroic acid, a known final metabolite of C-24 oxidation pathway. In
      addition to the C-24 oxidation pathway, human CYP24A1 catalyzed also C-23
      oxidation pathway to produce 1alpha,25(OH)2D3-26,23-lactone. Surprisingly, more
      than 70 % of the vitamin D metabolites observed in a living body were found to be
      the products formed by the activities of CYP27A1, CYP27B1 and CYP24A1. The
      species-based difference was also observed in the metabolism of vitamin D analogs
      by CYP24A1, suggesting that the recombinant system for human CYP24A1 may be of
      great use for the prediction of the metabolism of vitamin D analogs in humans.

PMID- 15574356
TI  - Quantification of HIV GAG RNA using real time reverse transcriptase PCR.
AB  - Quantification of HIV-1 is important to quantify risk for disease progression as
      well as for acquiring infection associated with drug abuse. Prior quantification
      methods include immune and enzymatic procedures, e.g., quantifying HIV-1 p24
      protein by ELISA and the Reverse Transcriptase by enzymatic assay. Improved
      quantification of HIV-1 RNA and cDNA was established using PCR. This paper
      describes a real-time PCR technique using the Applied Biosystems 5700 Sequence
      Detection System and Taqman reverse transcriptase PCR. We initially standardized
      the PCR method using ribosomal-RNA to obtain relative quantification. Pure gag
      RNA was used for standard curves, controls, and to obtain absolute RNA
      quantification. Pure HIV gag RNA was produced by T7-directed transcription of the
      plasmid pWISP98-85. Detailed statistical analyses describe using absolute
      standard curves, and intraassay and interassay coefficients of variation to
      validate the methods. The presented method is highly reproducible and the assay's
      performance is comparable to prior assays. The assay is validated with an 8-log
      range down to 80 copies.

PMID- 15574357
TI  - Role of protein kinases in neurodegenerative disease: cyclin-dependent kinases in
      Alzheimer's disease.
AB  - Cyclin-dependent kinases (Cdks) are serine/threonine kinases that regulate a
      number of cellular processes including the cell cycle and neuronal
      differentiation. Accumulating evidence indicates that two distinct Cdk pathways
      may have a role in the neuronal loss that is responsible for Alzheimer's disease.
      One pathway involves the aberrant reactivation of the cell cycle, a process
      believed to be incompatible with neuronal function. A second involves
      dysregulation of Cdk5, a member of this kinase family with no known cell cycle
      functions, but prominently expressed in postmitotic neurons. Reports supporting
      the involvement of both pathways are plentiful, but the story is not yet
      complete. In particular, difficulties incorporating the extended latency of AD
      into model approaches persist. Despite this, the theory that Cdks are involved in
      the pathogenesis of AD has generated considerable interest.

PMID- 15574358
TI  - Identification of myristoylated alanine-rich C kinase substrate (MARCKS) in
      astrocytes.
AB  - We have characterized membrane-associated substrates of Ca2+-dependent kinases in
      primary rat astrocytes by in vitro phosphorylation, 2-dimensional gel
      electrophoresis and autoradiography. The most prominent among these were three
      acidic, protein kinase C (PKC) substrates. These are important because they
      likely transduce cytokine and other neuro-immune modulatory signals mediated by
      PKC. We now show that one of these phosphoproteins is myristoylated alanine-rich
      PKC kinase substrate (MARCKS) or phosphomyristin C. The identity was corroborated
      by one- and 2- dimensional immunoblotting with an MARCKS-specific polyclonal
      antibody. Exposing primary astrocytes to phorbol 12-myristate 13-acetate
      stimulated phosphorylation of this protein. The level of MARCKS appeared
      inversely proportional to the proliferative potential of astrocytes because it
      was lower in spontaneously transformed as compared to passaged or confluent
      cells. These data are consistent with previous reports and indicate that one of
      three major acidic membrane-associated PKC substrates in astrocytes is MARCKS.
      Thus, MARCKS is likely near-proximal transducer of PKC-mediated signals in
      astrocytes.

PMID- 15574359
TI  - Microsensors and microbiosensors for retinal implants.
AB  - This paper concentrates on recent developments in microsensors and
      microbiosensors for the possible applications in visual prostheses, especially
      retinal prosthetic devices. A brief introduction on the developments of visual
      prosthesis will be presented. The importance for in-vivo pH measurements as well
      as the need for an implantable pH sensor will be demonstrated. Electrochemical
      biosensors developed for sensitive measurements of glucose and L-glutamate, a
      known neurotransmitter in the retina and brain will be reviewed. Novel electrode
      materials such as chemically modified thin-film diamond in applications for
      implantable biosensors will be shown. The challenges in the development of
      chronic implantable sensor systems, especially using MEMS technology for medical
      implants, will be discussed.

PMID- 15574360
TI  - Impedance labelless detection-based polypyrrole DNA biosensor.
AB  - Microelectrodes were fabricated to study impedance labelless detection of DNA
      hybridization. The probe molecule was attached onto the platinum microelectrode
      surface by electrochemically copolymerizing pyrrole and the probe
      oligonucleotides. Measured impedance complexes showed that an electrochemical
      redox-reaction occurred and the electron-transfer resistance increased after DNA
      hybridization. It was proposed that the hybridization of DNA in the conductive
      polymer matrix slowed down the anionic doping/undoping process, resulting
      impedance changes for the target DNA detection. Impedance measurements were
      conducted at the complementarily hybridized probe oilgomer-attached polypyrrole
      film electrodes in different anionic solutions to exam the anionic effects.
      Results showed that higher concentration and smaller size of anions had the lower
      electron-transfer resistance. The results not only provide further evidence to
      support the detection mechanism proposed, but also offer a method to improve the
      signal to noise ratio for the DNA biosensor. The research also tested the
      specificity of the methods and experimental results, indicating good specificity
      of the method. A concept array chip was fabricated and used to demonstrate the
      capability of the labelless detection method. Nano-Molar concentrations were
      detected and showed fairly linear responses versus the target molecule
      concentrations. The method is simple and inexpensive. The technique based
      genosensors could have potential applications in clinical diagnosis, drug
      discovery, environmental and food analysis.

PMID- 15574361
TI  - A three-generation approach in biodemography is based on the developmental
      profiles and the epigenetics of female gametes.
AB  - We suggest that there are three premises underlying the need for biodemographic
      analyses of three-generations: 1.) To describe the structure of the genome, we
      need to use (apart from mutations) other kinds of heritable changes such as those
      mediated by facultative elements (variations) and epigenetic alterations. 2.)
      There are many reasons to analyze individual development and its deviations, such
      as the biodemographic perspective of fertilization - but also including all long
      term intra-generational events of oogenesis and meiosis (beginning with the
      embryogenesis of the individual's mother - or during the grandmother's
      pregnancy). 3.) We need to explore the reality that every fertilized egg links -
      physically and genetically - three successive generations. We focus on genetic
      and epigenetic events, which start during egg cell lineage determination in F(n
      2) gestation and which influence the developmental profile of F(n) generation
      cohorts. The three-generation approach in epidemiology and biodemography is
      important so that we might increase our understanding of the effects of
      environmental forces, such as viral epidemics, and of catastrophes, such as the
      Chernobyl accident. It is also important for evaluating the processes of
      senescence and the determinants of human disease.

PMID- 15574362
TI  - The immune system in aging: roles of cytokines, T cells and NK cells.
AB  - Aging is characterized by a proinflammatory state that contributes to the onset
      of disability and age-related diseases. Proinflammatory cytokines play a central
      role in mediating cellular and physiological responses. The levels of these
      cytokines may reflect immune system effectiveness. Studies of the effects of
      aging on inflammatory response show interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to be important. In this
      review, age-related changes in inflammatory cytokines, T and NK cells, and the
      biology of IL-6 and TNF-alpha and their relevance to senescence are considered.

PMID- 15574364
TI  - Selective growth regulatory and pro-apoptotic effects of DIM is mediated by AKT
      and NF-kappaB pathways in prostate cancer cells.
AB  - Prostate cancer is the second leading cause of cancer related deaths in men in
      the United States. I3C and its in vivo dimeric product, DIM, have been found to
      inhibit the growth of prostate cancer cells. However, the molecular mechanism(s)
      by which DIM elicits its effects on prostate cancer cells has not been fully
      elucidated. We have previously shown that I3C induces apoptosis and inhibits the
      activation of NF-kappaB pathway, which could be mediated via Akt signaling
      pathway. In this study, we investigated whether there is any cross-talk between
      Akt and NF-kappaB during DIM-induced apoptosis in PC-3 prostate cancer cells. We
      found that DIM inhibited cell growth and induced apoptosis in PC-3 prostate
      cancer cells but not in non-tumorigenic CRL2221 human prostate epithelial cells.
      DIM also inhibited EGFR expression, PI3K kinase activity, and Akt activation, and
      abrogated the EGF-induced activation of PI3K in prostate cancer cells. NF-kappaB
      DNA-binding analysis and transfection studies with Akt cDNA constructs revealed
      that Akt transfection resulted in the induction of NF-kappaB activity and this
      was inhibited by DIM treatment. DIM treatment also showed significant induction
      of apoptosis in non-transfected cells compared to Akt and Akt-Myr transfected
      prostate cancer cells. From these results, we conclude that the inhibition of Akt
      and NF-kappaB activity and their cross-talk is a novel mechanism by which DIM
      inhibits cell growth and induces apoptotic processes in prostate cancer cells but
      not in non-tumorigenic prostate epithelial cells.

PMID- 15574365
TI  - Opioid-somatostatin interactions in regulating cancer cell growth.
AB  - Opioids and somatostatin mediate their cellular effects through specific membrane
      receptors. Three major receptor classes (delta, mu and kappa) were identified for
      opioids, while for somatostatin, five different receptor classes (SSTR1-5) have
      been cloned. Through the interaction with their receptors, opioids and
      somatostatin exert their effects on cell growth, proliferation, differentiation
      and secretion. Specific actions of each receptor type have been reported, to be
      implicated in one or more of the cell functions referred above but have been
      mainly correlated with cell growth control. In several systems the effect of
      either neuropeptide is the reverse, inducing cell growth rather than
      antiproliferative and proapoptotic signals. In recent years, a growing number of
      reports indicate a possible interaction between opioid and somatostatin system.
      This could occur at the receptor level, through a cross-interaction of either
      neuropeptide with either receptor type, or receptor hetero-dimerization, and at a
      post-receptor level, via interaction with specific signaling molecules. These
      interactions provide new directions for the identification of specific molecules
      acting at the receptor and post-receptor level, mimicking the effects of both
      categories of agents.

PMID- 15574366
TI  - Estrogen and brain: synthesis, function and diseases.
AB  - This review summaries recent evidence from clinical and basic science studies on
      estrogen central nervous system. For decades, estrogen was thought of only as a
      "sex hormone" and plays a fundamental role in regulating behavioral and
      physiological events. In recent years, accumulated evidence shows that estrogen
      also plays very important roles in the brain. Recent basic science studies show
      that estrogen treatment decreases the neuronal response to various forms of
      insult through the regulation of both estrogen synthesis and estrogen receptor
      expression in the brain. Some clinical evidence also suggests that estrogen
      deprivation might be implicated as a risk factor in various neurodegenerative
      diseases. Estrogen may play a neuroprotective role through estrogen dependent
      alterations in cell survival, enhancement of synaptic transmission and
      neurogenesis. Some of the mechanisms underlying these effects are independent of
      the classical nuclear estrogen receptors and involve direct modulation of
      neurotransmitter receptor function, or anti-oxidant activities of estrogen. It is
      controversial whether estrogen is indicated in the prevention or treatment of
      various brain disorders such as Alzheimer's disease. The conflicting findings
      suggest that several variables, including age, estrogen dose and formulation, the
      length of treatment, may determine whether the potential benefits of estrogen
      treatment would outweigh the associated risks.

PMID- 15574363
TI  - Pathobiology of dynorphins in trauma and disease.
AB  - Dynorphins, endogenous opioid neuropeptides derived from the prodynorphin gene,
      are involved in a variety of normative physiologic functions including
      antinociception and neuroendocrine signaling, and may be protective to neurons
      and oligodendroglia via their opioid receptor-mediated effects. However, under
      experimental or pathophysiological conditions in which dynorphin levels are
      substantially elevated, these peptides are excitotoxic largely through actions at
      glutamate receptors. Because the excitotoxic actions of dynorphins require
      supraphysiological concentrations or prolonged tissue exposure, there has likely
      been little evolutionary pressure to ameliorate the maladaptive, non-opioid
      receptor mediated consequences of dynorphins. Thus, dynorphins can have
      protective and/or proapoptotic actions in neurons and glia, and the net effect
      may depend upon the distribution of receptors in a particular region and the
      amount of dynorphin released. Increased prodynorphin gene expression is observed
      in several disease states and disruptions in dynorphin processing can accompany
      pathophysiological situations. Aberrant processing may contribute to the net
      negative effects of dysregulated dynorphin production by tilting the balance
      towards dynorphin derivatives that are toxic to neurons and/or oligodendroglia.
      Evidence outlined in this review suggests that a variety of CNS pathologies alter
      dynorphin biogenesis. Such alterations are likely maladaptive and contribute to
      secondary injury and the pathogenesis of disease.

PMID- 15574367
TI  - Surface plasmon resonance spectroscopy and quartz crystal microbalance study of
      MutS binding with single thymine-guanine mismatched DNA.
AB  - MutS is a DNA mismatch binding protein that recognizes heteroduplex DNA
      containing mispaired or unpaired bases. In this study, we employ a quartz crystal
      microbalance (QCM) and a surface plasmon resonance (SPR) device for the study of
      MutS binding with DNA containing a single Thymine-Guanine (T-G) mismatch at
      different sites. Multi-step surface binding reactions are involved in the study,
      including probe DNA immobilization on the sensor surface through biotin
      streptavidin-biotin bridge chemistry, target DNA hybridization to form T-G
      heteroduplexes, and MutS recognition of the mutation sites. The QCM frequency (d
      f) and motional resistance (d R, an impedance parameter reflective of QCM
      damping), as well as the SPR angle shift (d q ) are recorded for the binding
      reactions. The combined SPR and QCM data collection and analysis allow for an
      assessment of not only the amount of bound biopolymer but provide also
      information on also the structural properties of the streptavidin, DNA and
      MutS/DNA complexes. The affinity of the MutS/T-G heteroduplex assembly is
      determined by both the QCM and SPR methods through titration of the surface bound
      DNA with increasing MutS concentration. It is found that if the T-G mismatch is
      in the center of the DNA fragment, the MutS/DNA complex is more stable than if
      the mismatch is located near the end of the fragment.

PMID- 15574368
TI  - Polyoxometalates: introduction to a class of inorganic compounds and their
      biomedical applications.
AB  - An increasing number of potential applications for polyoxometalates in human
      medicine have been reported in the literature. These inorganic complexes are
      composed of early transition metals (mainly molybdenum, tungsten and vanadium)
      and oxygen. The present review gives an introduction into the chemistry of these
      compounds, and an overview of the principal studies of their biological and
      biochemical effects and their therapeutic potential. The reported antitumoral and
      antibiotic properties of molybdates and tungstates in vitro and in vivo are
      compiled and discussed, as are their influences on the blood glucose level in
      diabetic animals. Aspects of antiviral activities and cell penetration are
      treated.

PMID- 15574369
TI  - A protein family under 'stress' - serpin stability, folding and misfolding.
AB  - The native fold of inhibitory serpins (serpin proteinase inhibitors) is
      metastable and therefore does not represent the most stable conformation that the
      primary sequence encodes for. The most stable form is adopted when the reactive
      centre loop (RCL) inserts, as the fourth strand, into the A b -sheet. Currently a
      serpin can adopt at least four more stable conformations, termed the cleaved,
      delta, latent and polymeric states. The accessibility of these alternative low
      energy folds renders the serpin molecule susceptible to mutations that can result
      in dysfunction and pathology. Here, we discuss the means by which the serpin can
      attain and preserve this metastable conformation. We also consider the triggers
      for misfolding to these more stable states and the mechanisms by which it occurs.

PMID- 15574370
TI  - S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen
      receptors.
AB  - The defining characteristic of a tumor cell is its ability to escape the
      constraints imposed by neighboring cells, invade the surrounding tissue and
      metastasize to distant sites. This invasive property of tumor cells is dependent
      on activation of proteinases at the cell surface. The serine proteinase plasmin
      is one of the key proteinases that participate in the pericellular proteolysis
      associated with the invasive program of tumor cells. The assembly of plasminogen
      and tissue plasminogen activator at the endothelial cell surface or on the fibrin
      clot provides a focal point for plasmin generation and therefore plays an
      important role in maintaining blood fluidity and promoting fibrinolysis. S100A10,
      a member of the S100 family of Ca2+-binding proteins, is a dimeric protein
      composed of two 11 kDa subunits. Typically, S100A10 is found in most cells bound
      to its annexin A2 ligand as the heterotetrameric (S100A10)2(annexin A2)2 complex,
      AIIt. In addition to an intracellular distribution, S100A10 is present on the
      extracellular surface of many cells. The carboxyl-terminal lysines of S100A10
      bind tPA and plasminogen resulting in the stimulation of tPA-dependent plasmin
      production. Carboxypeptidases cleave the carboxyl-terminal lysines of S100A10,
      resulting in a loss of binding and activity. Plasmin binds to S100A10 at a
      distinct site and the formation of the S100A10-plasmin complex stimulates plasmin
      autoproteolysis thereby providing a highly localized transient pulse of plasmin
      activity at the cell surface. The binding of tPA and plasmin to S100A10 also
      protects against inhibition by physiological inhibitors, PAI-1 and alpha2
      antiplasmin, respectively. S100A10 also colocalizes plasminogen with the uPA-uPAR
      complex thereby localizing and stimulating uPA-dependent plasmin formation to the
      surface of cancer cells. The loss of S100A10 from the extracellular surface of
      cancer cells results in a significant loss in plasmin generation. In addition,
      S100A10 knock-down cells demonstrate a dramatic loss in extracellular matrix
      degradation and invasiveness as well as reduced metastasis. Annexin A2 plays an
      important role in plasminogen regulation by controlling the levels of
      extracellular S100A10 and by acting as a plasmin reductase. The mechanism by
      which annexin A2 regulates the extracellular levels of S100A10 is unknown. This
      review highlights the important part that S100A10 plays in plasmin regulation and
      the role this protein plays in cancer cell invasiveness and metastasis.

PMID- 15574371
TI  - Direct proteins electrochemistry based on ionic liquid mediated carbon nanotube
      modified glassy carbon electrode.
AB  - A novel glassy carbon electrode modified by a gel containing multi-walled carbon
      nanotubes (MWNTs) and ionic liquid of 1-butyl-3-methylimidazolium
      hexafluorophosphate (BMIPF6) is reported. The gel is formed by grinding of MWNTs
      and BMIPF6. Such gel is then coated on the surface of a glassy carbon electrode.
      We have employed scanning electron microscopy, Fourier transform infrared
      spectrometry (FTIR) and cyclic voltammetry to characterize the modified
      electrode. The direct electron transfers of hemoglobin and catalase on the
      modified electrode have been observed and studied in detail electrochemically.
      Hemoglobin is verified to be adsorbed on the modified electrode with the
      retention of conformation, which has been proved by microscopic FTIR. The
      electrochemical response of the adsorbed hemoglobin on the modified electrode is
      very stable, and shows repeated changes in the different pH solutions. It also
      has shown electrocatalysis to the reduction of oxygen and trichloroacetic acid.
      Catalase adsorbed on the gel modified electrode still keep activity to hydrogen
      peroxide. This work provides a simple and easy approach to construct biosensors
      based on the carbon nanotubes and ionic liquids.

PMID- 15574372
TI  - Genome organization and three kinds of heritable changes: general description and
      stochastic factors (a review).
AB  - Due to the increased knowledge of genome architecture, topology, and the
      mechanisms of hereditary variability, the list of genetic components has grown.
      This review outlines the general features and principles of genome organization
      in diverse organisms. The genome codes, stores, and transfers information in both
      structurally and dynamically. The genome includes two subsystems of genetic
      elements: obligatory (genes and gene families) and various types of facultative
      elements which are predominant the content of the human genome. The features of
      three kinds of heritable changes: mutations, variations (changes in the number or
      topography of facultative elements), and epigenetic alterations are described.
      Facultative elements are the first to react to environmental challenges. Together
      with epigenetic changes, they implement the operational genomic memory. This
      review discusses both the role of stochastic factors and the transient features
      of DNA components.

PMID- 15574373
TI  - Enzyme-based amperometric biosensors for continuous and on-line monitoring of
      cerebral extracellular microdialysate.
AB  - Analytical systems integrating in vivo microdialysis sampling with enzyme-based
      electrochemical biosensor detection have been increasingly accepted to be a new
      technique for continuous and on-line monitoring of biologically important
      species. Extensive interests in such integrated on-line analytical systems have
      suggested that these systems are very useful for physiological and pathological
      investigations. This review mainly focuses on the principle, development and
      striking applications of the enzyme-based amperometric biosensors integrated with
      in vivo microdialysis for continuous and on-line monitoring of cerebral
      extracellular fluid in recent years.

PMID- 15574374
TI  - The role and regulation of the uterine matrix metalloproteinase system in
      menstruating and non-menstruating species.
AB  - The uterus undergoes dynamic tissue remodeling throughout each reproductive
      cycle, which is regulated in part by the matrix metalloproteinases (MMP) system.
      The MMP system is comprised of the proteolytic factors, the MMPs, and their
      tissue inhibitors (TIMPs), which act in concert to modulate extracellular matrix
      turnover and cell behaviors and thus play a key role in many physiologic and
      pathologic conditions throughout the body. MMPs and TIMPs are expressed
      spatiotemporally in the uterus of various menstruating and non-menstruating
      species. The balanced function of the MMP system is critical to normal uterine
      tissue remodeling throughout the cycle as well as during pregnancy, parturition
      and postpartum uterine involution. The uterine MMP system appears to be under the
      regulation of not only ovarian steroids but also various autocrine/paracrine
      factors such as growth factors, cytokines and chemokines. The current review
      focuses on the expression and regulation of the MMP system within the uterus
      during the menstrual or estrous cycle, and addresses the roles of various MMPs
      and TIMPs in uterine biology.

PMID- 15574375
TI  - Managing chronic pain with encapsulated cell implants releasing catecholamines
      and endogenous opiods.
AB  - Spinal injections (intrathecal) of norepinephrine and/or opiod agonists are
      antinociceptive and when administered together may act in synergy. Spinal
      implants of adrenal chromaffin cells are an effective method for sustained
      delivery of the analgesic substances norepinephrine and enkephalin to the central
      nervous system (CNS). One method of packaging and implanting cell-loaded devices
      into the intrathecal space of recipients is by encapsulating the cell suspensions
      in a polymer membrane prior to implantation. Cells/tissue packaged within an
      encapsulating membrane obviate the need for immunosuppressive therapies in
      transplant recipients. In addition, device output can be quantified prior to
      implantation, and following the removal of the spinal implant. The ability to
      retrieve the devices with the present tubular configuration also confers an
      additional margin of safety over unencapsulated chromaffin cell implants. This
      paper reviews the research and clinical observations of cellular transplants
      containing adrenal chromaffin cells for relieving chronic pain. Encapsulated cell
      technology is discussed with an emphasis on our experiences developing pain
      modulating clinical devices. The human-sized prototype devices were loaded with
      enzymatically isolated bovine chromaffin cells and maintained in vitro for 7 - 8
      days in serum-free media. Two days prior to implantation, each device was assayed
      by static incubation to measure catecholamine and met-enkephalin output, and
      qualified devices (n = 6) were implanted into the sheep subarachnoid space for 6
      weeks. Following a 6 week in life period, the retrieval forces of prototype
      devices were measured during removal from the subarachnoid space. Static
      incubation of the devices immediately following retrieval and after a 24 hour re
      incubation period were used to quantify norepinephrine and met-enkephalin
      secretion profiles. This study demonstrated the safety, retrievability and
      maintenance of pharmacologically active encapsulated chromaffin cell-loaded
      devices with human implant dimensions.

PMID- 15574376
TI  - Micromechanics of tumor cell adhesion and migration under dynamic flow
      conditions.
AB  - Attachment of tumor cells to endothelial cells is critical for migration of tumor
      cells out of the vascular system to establish metastases. We have studied human
      melanoma cell (C8161) adhesion and migration in response to stimulation by
      soluble collagen IV (CIV) using a modified Boyden chamber. In this modified
      chamber, shear flow can be introduced over the cell-substrate interface affecting
      tumor cell chemotactic migration through a microporous filter. Our results
      suggest that transmigration of C8161 cells under flow conditions can be
      influenced by PMNs, mediated by Mac-1 and ICAM-1 adhesive interactions and
      enhanced by altered cytokine production.

PMID- 15574377
TI  - A case study of proline isomerization in cell signaling.
AB  - Protein-mediated interactions and enzymatic function provide the foundation upon
      which cellular signaling cascades control all of the activities of a cell. Post
      translational modifications such as phosphorylation or ubiquitiation are well
      known means for modulating protein activity within the cell. These chemical
      modifications create new recognition motifs on proteins or shift conformational
      preferences such that protein catalytic and binding functions are altered in
      response to external stimuli. Moreover, detection of such modifications is often
      straightforward by conventional biochemical methods leading investigators toward
      mechanistic models of cell signaling involving post-translational modifications
      such as phosphorylation/dephosphorylation. While there is little doubt that such
      modifications play a significant role in transmission of information throughout
      the cell, there are certainly other mechanisms at work that are not as well
      understood at this time. Of particular interest in the context of this review is
      the intrinsic conformational switch afforded to a polypeptide by peptidyl prolyl
      cis/trans isomerization. Proline isomerization is emerging as a critical
      component of certain cell signaling cascades. In addition to serving as a
      conformational switch that enables a protein to adopt functionally distinct
      states, proline isomerization may serve as a recognition element for the
      ubiquitous peptidyl prolyl isomerases. This overview takes a close look at one
      particular signaling protein, the T cell specific tyrosine kinase Itk, and
      examines the role of proline isomerization and the peptidyl prolyl isomerase
      cyclophilin A in mediating Itk function following T cell receptor engagement.

PMID- 15574378
TI  - Cadherin-mediated cell-cell adhesion in the testis.
AB  - During spermatogenesis, the differentiating germ cells migrate across the
      seminiferous epithelium while maintaining close contact with the surrounding
      Sertoli cells via specialized actin-based adherens junctions (ectoplasmic
      specializations) and intermediate filament-based anchoring junctions (desmosome
      like junctions). Although this migration is essential for correct completion of
      spermatogenesis, the mechanisms that regulate these anchoring junctions are
      largely unknown, and most of our knowledge of cell-cell adhesion in testis is
      based on earlier studies in epithelial tissues. In most epithelia, members of the
      cadherin superfamily play key roles in intercellular adhesion. Cadherins are
      calcium-dependent cell-cell adhesion molecules mediating numerous homotypic cell
      cell interactions. Until recently there has been controversy about the presence
      and localization of cadherins in the testis, but now there is increasing evidence
      that various types of cadherins are expressed in this organ, which underscores
      their importance in testicular functions. Here, we review the expression
      patterns, regulatory mechanisms and possible roles of the cadherin-mediated cell
      cell adhesion in the testis, and particularly during spermatogenesis. Moreover,
      attention is paid to additional molecular adhesion complexes in the testis, to
      associated signaling pathways and to cell adhesion-related innovative ways for
      male contraception.

PMID- 15574379
TI  - Analytical aspects of fet-based biosensors.
AB  - Field-effect transistor (FET)-based biosensors (BioFETs) have undergone great
      progress especially in the last decade, since they were first realized in 1980.
      Recently, BioFETs have become one of the most important branches of biosensors.
      This paper briefly reviewed the operating principles of BioFETs and summarized
      the improvement and application of BioFETs, finally, the future prospects of
      BioFETs were discussed with 126 references.

PMID- 15574381
TI  - Matrix composition of cartilaginous anlagen in achondrogenesis type II (Langer
      Saldino).
AB  - Skeletal dysplasias represent in vivo models of genetic defects. Achondrogenesis
      type II (Langer-Saldino), caused by a genetic defect in the major cartilage
      matrix protein, collagen type II, is a rare and severe skeletal dysplasia. It
      comprises a severe derangement of the fetal growth plate cartilage with
      subsequent ossification defects. In this study, we analyzed the matrix
      composition and cell differentiation pattern in 3 relatives with achondrogenesis
      type II. Most strikingly we found a strongly reduced collagen type II and
      moderately reduced aggrecan proteoglycan content in the dysplastic cartilage
      matrix. Type II collagen is, at least to some extent, replaced by collagens type
      I III, and VI. Ultrastructural analysis of the dysplastic cartilage matrix
      demonstrated a distended rER (rough endoplasmic reticulum), which is typical for
      this condition and most likely related to improper processing and retention of
      genetically altered type II collagen. Immunostaining for type IIA and X collagens
      suggest a severe delay in chondrocyte maturation. Thus, the genetic defect in the
      present cases leads most likely to a severe retention of collagen type II in the
      rER and, therefore, a strongly reduced collagen deposition and replacement by
      other interstitial collagens. However, the latter are less efficient in binding
      aggrecan proteoglycans in the dysplastic cartilage matrix. Additionally, a delay
      in chondrocyte maturation appears to be important in achondrogenesis type II.

PMID- 15574382
TI  - Nitric oxide in neurodegenerative diseases.
AB  - Nitric oxide (NO) free radical as a major signaling molecule in nervous systems
      has been shown to have close relationship with neurodegenerative diseases. The
      results about the relation of NO and neurodegenerative diseases, such as
      Alzheimer's disease (AD), Parkinson's disease (PD) and stroke in recent years are
      reviewed. Particularly, the results of antioxidants and NO in neurodegenerative
      disorders from author's own laboratory are included in this paper.

PMID- 15574383
TI  - Cytoplasmic membrane iron permease systems in the bacterial cell envelope.
AB  - Iron is a vital nutrient for the vast majority of organisms. Gram-positive
      bacteria, Gram-negative bacteria and archaea established different strategies to
      utilize iron from various sources. This article concentrates on the cytoplasmic
      membrane-associated uptake systems involved in the acquisition of iron. Genetic,
      biochemical and structural data as well as computational analyses were taken into
      consideration. Besides divalent metal transporters of the Nramp type and ferrous
      iron transport proteins of the Feo type, four distinct families of ABC
      transporters related to iron uptake are known. Their components mediate the
      transfer of iron, siderophores, heme and vitamin B12 into the cytosol of
      prokaryotes.

PMID- 15574384
TI  - Immune peptide enhancement of peptide based vaccines.
AB  - Vaccines optimize the presentation of an immunogen to the immune system,
      oftentimes enhancing or replacing the natural activators of antigen presenting
      cells in order to promote the delivery and the response of T and B lymphocytes to
      the immunogen. The purpose of this series is to describe new technologies which
      allow vaccine design, based on our understanding of the immune response, using
      different approaches to immune peptide enhancement of peptide based vaccines. In
      this introduction to the series entitled, "Immune Peptide Enhancement of Peptide
      Based Vaccines", some of the immunological concepts relevant to vaccine design
      are presented.

PMID- 15574380
TI  - The human T-cell leukemia virus Rex protein.
AB  - A critical step in the life cycle of complex retroviruses, including HTLV-1 and
      HTLV-2 is the ability of these viruses to adopt a mechanism by which the genome
      length unspliced mRNA as well as the partially spliced mRNAs are exported from
      the nucleus instead of being subjected to splicing or degradation. In HTLV, this
      is accomplished through the expression of the viral Rex, which recognizes a
      specific response element on the incompletely spliced mRNAs, stabilizes them,
      inhibits their splicing, and utilizes the CRM1-dependent cellular pathway for
      transporting them from the nucleus to the cytoplasm. Rex itself is regulated by
      phosphorylation, which implies that proper activation of the protein in response
      to certain cellular cues is an important tool for the virus to ensure that
      specific viral gene expression is allowed only when the host cell can provide the
      best conditions for virion production. Having such a critical role in HTLV life
      cycle, Rex is indispensable for efficient viral replication, infection and
      spread. Indeed, Rex is considered to regulate the switch between the latent and
      productive phases of the HTLV life cycle. Without a functional Rex, the virus
      would still produce regulatory and some accessory gene products; however,
      structural and enzymatic post-transcriptional gene expression would be severely
      repressed, essentially leading to non-productive viral replication. More detailed
      understanding of the exact molecular mechanism of action of Rex will thus allow
      for better design of therapeutic drugs against Rex function and ultimately HTLV
      replication. Herein we summarize the progress made towards understanding Rex
      function and its role in the HTLV life cycle.

PMID- 15574385
TI  - Nickel hexacyanoferrate modified screen-printed carbon electrode for sensitive
      detection of ascorbic acid and hydrogen peroxide.
AB  - Electrochemically modified screen-printed carbon electrode (SPCE) has been
      prepared by electrodepositing nickel hexacyanoferrate(III) (NiHCF) onto the
      electrode surface using cyclic voltammetry (CV). The performance of NiHCF-SPCE
      sensor was characterized and optimized by controlling several operational
      parameters. The NiHCF film has been proven to remain stable after CV scanning
      from 0 to +1.0 V vs. Ag/AgCl in the pH range of 3 to 10 and is re-useable. The
      most favourable supporting electrolyte solution exhibiting the optimum
      electroanalytical performance of the NiHCF-SPCE sensor was found to be 0.2 mol/L
      sodium nitrate. The electrochemical response toward ascorbic acid (AA) and H2O2
      in 0.2 mol/L sodium nitrate solution was studied by using CV and the results
      showed that both analytes were electrocatalytically oxidized at approximately
      +0.4 V, while H2O2 also revealed a reduction signal at -0.8 V vs. Ag/AgCl. The
      NiHCF-SPCE sensor exhibited highly linear response for AA and H2O2 in the
      examined concentration range from 5.0x10-5 to 1.5x10-3 mol/L and from 2.0x10-5 to
      1.0x10-3 mol/L (at +0.4 V), with the correlation coefficients of 0.999 and 0.998,
      respectively. The reproducibility of the NiHCF-SPCE sensor was followed for the
      determination of AA by using four individual electrodes, and the relative
      standard deviation of CV peak currents varied between 0.9 % and 2.2 %. The
      proposed NiHCF-SPCE has been shown to be a very attractive electrochemical sensor
      for AA and H2O2, also in a view of inexpensive mass production of disposable
      single-use sensors. The NiHCF-SPCE sensor was tested by measuring AA in
      multivitamin tablets, with recoveries obtained between 94.4 % and 108.2 % (n=5).

PMID- 15574386
TI  - Carbon nanotubes (CNTs) for the development of electrochemical biosensors.
AB  - Carbon nanotube (CNT) is a very attractive material for the development of
      biosensors because of its capability to provide strong electrocatalytic activity
      and minimize surface fouling of the sensors. This article reviews our recent
      developments of oxidase- and dehydrogenase-amperometric biosensors based on the
      immobilization of CNTs, the co-immobilization of enzymes on the CNTs/Nafion or
      the CNT/Teflon composite materials, or the attachment of enzymes on the
      controlled-density aligned CNT-nanoelectrode arrays. The excellent
      electrocatalytic activities of the CNTs on the redox reactions of hydrogen
      peroxide, nicotinamide adenine dinucleotide (NADH), and homocysteine have been
      demonstrated. Successful applications of the CNT-based biosensors reviewed herein
      include the low-potential detections of glucose, organophosphorus compounds, and
      alcohol.

PMID- 15574387
TI  - The transcription factor Ets-1 in breast cancer.
AB  - The proto-oncogene Ets-1 is a member of the Ets family of transcription factors
      which share a unique DNA binding domain, the Ets domain. Ets binding sites have
      been described on the promoters or enhancers of many proteinases and several Ets
      members transcriptionally regulate such promoters in transient cotransfection
      assays. Ets-1 is involved in both normal and pathological functions. Ets-1 is
      expressed in a variety of cells, including endothelial cells, vascular smooth
      muscle cells and epithelial cells. Ets-1 regulates the expression of several
      angiogenic and extracellular matrix remodeling factors promoting an invasive
      phenotype. The Ets family of transcription factors may play a role in the disease
      progression of breast cancer. In tumors, including breast neoplasia, Ets-1
      expression is indicative of poorer prognosis. This review will summarize the role
      of Ets-1 in both the tumor cells, and the tumor endothelial cells as it relates
      to breast tumor growth and spread.

PMID- 15574388
TI  - Coil-type implantable glucose biosensor with excess enzyme loading.
AB  - As part of our overall long-term objective of designing a glucose sensor for long
      term subcutaneous implantation, a coil-type implantable glucose sensor loaded
      with excess glucose oxidase (GOD) inside the coils of a 0.125mm diameter coiled
      platinum-iridium wire has been developed. The excess GOD was immobilized in a
      glutaraldehyde/bovine serum albumin (BSA) gel reinforced with cotton and located
      inside the coils chamber of the sensor. The excess GOD increased the lifetime of
      the sensor. Based on this coil-type design, various coil-type glucose sensors
      with cellulose acetate (CA), poly(vinyl chloride)(PVC), polyurethane (PU),
      poly(bisphenol A carbonate) (PC) and Nafion outer membranes were investigated and
      compared. Comparatively, Nafion based biosensors provided the best long-term
      response stability. However, Nafion can still not meet the lifetime requirement
      of the coil-type sensor with high enzyme loading because the observed function
      failure of these sensors was indeed caused by outer membrane damage rather than
      loss of enzyme activity. Additional experiments also revealed that hydrogen
      peroxide accumulation occurred in the GOD impregnated cotton when the sensors
      were not polarized which could cause a small false positive measurement. However,
      this artifact can be easily avoided by using an appropriate measurement
      technique.

PMID- 15574389
TI  - Reagentless electrochemical biosensor based on the multi-wall carbon nanotubes
      and nanogold particles composite film.
AB  - A novel method was used to prepare the nano-composite by assembling nanogold (NG)
      particles on the multiwall carbon nanotubes (MWNTs) surface. The nano-composite
      could be immobilized on a glassy carbon (GC) electrode to get a novel modified
      electrode. The electrode can easily immobilize the horseradish peroxidase (HRP)
      molecules to construct a reagentless biosensor. The NG particles in the composite
      film have a good biological compatibility. And due to the existence of quinone
      groups on the MWNTs surface, the MWNTs can promote the electron transfer between
      enzymes and electrode surface. The biosensor shows a good stability and responds
      to H2O2 in the range from 2.0 microM to 3.5 mM with a detection limit of 1.0
      microM.

PMID- 15574390
TI  - Basic calcium phosphate crystals as a unique therapeutic target in
      osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of arthritis that occurs in humans.
      Despite its prevalence, the pathogenesis of OA is not fully understood.
      Intraarticular basic calcium phosphate (BCP) (an inclusive term for partially
      carbonate-substituted hydroxyapatite, octacalcium phosphate and tricalcium
      phosphate) crystals are implicated in OA and are associated with severe
      degenerative arthritis characterized by marked synovial hyperplasia, aggravated
      joint degeneration and large joint effusions. Their pathogenicity relates, at
      least in part, to their ability to stimulate cellular mitogenesis in a number of
      cell types including macrophages, porcine articular chondrocytes (PAC) and human
      fibroblasts (HF) and induce prostaglandin, cytokine and matrix metalloproteinase
      synthesis and secretion in HF and PAC. Identification of BCP crystals in OA
      joints remains problematic because of the lack of a simple and reliable analytic
      procedure. There is currently no drug available that prevents the formation or
      modifies the biological effects of BCP crystals. This review highlights the
      recent advances in our knowledge of BCP crystal deposition diseases and discusses
      the potential therapeutic strategies for BCP crystal-associated OA.

PMID- 15574391
TI  - Adhesion molecules for mouse primordial germ cells.
AB  - In the present article we will focus on the adhesion molecules expressed by mouse
      primordial germ cells (PGCs) and will discuss the role that they play, or are
      believed to play, in two crucial processes of PGC development, namely cell
      lineage specification and migration into the gonadal ridges. Recent findings
      indicate that the adhesion-dependent allocation of the PGC precursors to a niche
      within the epiblast and the forming extraembryonic mesoderm during the pre
      gastrulation period is crucial for their commitment. Subsequently, PGC migration
      and homing within the gonadal ridges require integrated signals involving contact
      of PGCs with extracellular matrix molecules and cellular substrates or repulsion
      from them, adhesion among PGCs themselves and attraction by the developing
      gonads. A number of adhesion, or putative adhesion molecules, have been
      identified in mammalian PGCs, mainly in the mouse. These molecules belong to
      three adhesion molecule families such as cadherins (E-P- and N-cadherins),
      integrins and the IgG superfamily (PECAM-1). Moreover oligosaccarides (LewisX)
      and growth factor receptors (c-Kit) can also play adhesive roles in some stages
      of PGC development. An understanding of how genes encoding adhesive molecules are
      regulated in PGCs and the molecular pathways associated with the functions of
      adhesion receptors is crucial in furthering our knowledge of PGC biology.
      Adhesion molecules might once again turn out to be crucial in controlling not
      only the germ cell lineage and PGC migration but also the PGC differentiation
      fate itself.

PMID- 15574392
TI  - Brain chemotherapy from the bench to the clinic: targeting neuronal survival with
      small molecule inhibitors of apoptosis.
AB  - Increasing evidence implicates aberrant apoptosis as a fundamental cause of
      neurodegenerative diseases. Thus elucidating the underlying causes of neuronal
      programmed cell death may foster the development of therapeutic interventions.
      Research in the last 15 years provided a solid foundation for understanding
      molecular mechanisms of neuronal apoptosis. This review discusses the major
      molecules and signaling pathways leading to neuronal survival or apoptosis with
      emphasis on several small molecule inhibitors that target neuronal survival with
      the hope of impeding the detrimental effects of neurodegenerative diseases.

PMID- 15574393
TI  - The relevancy of the matrix metalloproteinase system to the pathophysiology of
      endometriosis.
AB  - The matrix metalloproteinase (MMP) system is composed of the enzymatic component,
      the MMPs, and the enzyme inhibitory component, the tissue inhibitors of
      metalloproteinases or TIMPs. It is well established that the MMP system plays a
      critical role during the normal development and growth of the endometrium as well
      as many other physiological processes. Because of the necessity for the balance
      between MMP and TIMP, it is not surprising that aberrant expression of MMPs and
      TIMPs is associated with the pathophysiology of many diseases. Included in this
      list is the female disease endometriosis, a disease in which endometrial tissue
      grows outside of the uterus usually within the pelvic cavity. Both endometriotic
      (ectopic) endometrial tissue as well as the eutopic endometrium from women with
      the disease exhibit altered patterns of MMP and TIMP expression which favor
      tissue invasion/remodeling by the endometriotic tissue. As such, it has been
      proposed that successful modulation of the MMP system to limit or prevent the
      invasive events necessary for endometriosis development and/or progression may
      open new avenues to the medical management of endometriosis. This review will
      present general knowledge of the MMP system relative to the pathophysiology of
      the endometriosis as well as address its potential value in relation to the
      treatment of the disease.

PMID- 15574394
TI  - Annexins - their role in cartilage mineralization.
AB  - Annexins II, V and VI are highly expressed by hypertrophic and terminally
      differentiated growth plate chondrocytes and by osteoblasts. Because of the
      localization of annexins in areas of cartilage and bone mineralization, we
      hypothesized that these annexins play a regulatory role in the mineralization
      process. In this article we review the function of annexins II, V and VI in
      physiological mineralization of skeletal tissues and in pathological
      mineralization of articular cartilage.

PMID- 15574395
TI  - Environmental and physiological controls over oxygen and carbon isotope
      composition of Tasmanian blue gum, Eucalyptus globulus.
AB  - We measured oxygen isotope ratios (delta18O) of xylem sap, phloem sap, leaves,
      wood and bark of Eucalyptus globulus Labill. growing in southwestern Australia.
      Carbon isotope ratios (delta13C) were measured in the dry matter of phloem sap,
      leaves and wood. Results were used to test several aspects of a mechanistic model
      of 18O enrichment and provided insights into post-photosynthetic variations in
      dry matter delta13C. Xylem water delta18O varied little within the tree crown,
      whereas variation at the landscape-level was more pronounced, with plantations
      near the coast being enriched by up to 3 per thousand compared with plantations
      less than 100 km inland. Phloem water was significantly enriched in 18O compared
      with xylem water in two of three sampling campaigns; mean enrichments were 0.5
      and 0.8 per thousand. Phloem sap sugars exported from E. globulus leaves closely
      reflected observed leaf water enrichment when diurnal variation in photosynthesis
      was taken into account. Photosynthetic rates were higher in the morning than in
      the afternoon, whereas leaf water 18O enrichment increased to maximum values in
      the afternoon. A non-steady-state model of leaf water 18O enrichment accurately
      predicted observed values through a full diel cycle. Mean estimates of the
      proportion of organic oxygen effectively exchanging with xylem water during
      cellulose synthesis were close to 0.40 for both leaves and wood. Carbon isotope
      ratios of nascent xylem tissues did not differ from those of phloem sap sugars
      collected concurrently, whereas nascent leaf tissues were depleted in 13C by 2
      per thousand compared with phloem sap sugars, suggesting that, in E. globulus,
      13C enrichment of sink tissues compared with source leaves does not result from
      an enriching process within the sink tissue.

PMID- 15574396
TI  - Modeling tree water deficit from microclimate: an approach to quantifying drought
      stress.
AB  - Tree water deficit estimated by measuring water-related changes in stem radius
      (DeltaW) was compared with tree water deficit estimated from the output of a
      simple, physiologically reasonable model (DeltaWE), with soil water potential
      (Psisoil) and atmospheric vapor pressure deficit (VPD) as inputs. Values of
      DeltaW were determined by monitoring stem radius changes with dendrometers and
      detrending the results for growth. We followed changes in DeltaW and DeltaWE in
      Pinus sylvestris L. and Quercus pubescens Willd. over 2 years at a dry site (2001
      2002; Salgesch, Wallis) and in Picea abies (L.) Karst. for 1 year at a wet site
      (1998; Davos, Graubuenden) in the Swiss Alps. The seasonal courses of DeltaW in
      deciduous species and in conifers at the same site were similar and could be
      largely explained by variation in DeltaWE. This finding strongly suggests that
      DeltaW, despite the known species-specific differences in stomatal response to
      microclimate, is mainly explained by a combination of atmospheric and soil
      conditions. Consequently, we concluded that trees are unable to maintain any
      particular DeltaW. Either Psisoil or VPD alone provided poorer estimates of
      DeltaW than a model incorporating both factors. As a first approximation of
      DeltaWE, Psisoil can be weighted so that the negative mean Psisoil reaches 65 to
      75% of the positive mean daytime VPD over a season (Q. pubescens: approximately
      65%, P. abies: approximately 70%, P. sylvestris: approximately 75%). The
      differences in DeltaW among species can be partially explained by a different
      weighting of Psisoil against VPD. The DeltaW of P. sylvestris was more dependent
      on Psisoil than that of Q. pubescens, but less than that of P. abies, and was
      less dependent on VPD than that of P. abies and Q. pubescens. The model worked
      well for P. abies at the wet site and for Q. pubescens and P. sylvestris at the
      dry site, and may be useful for estimating water deficit in other tree species.

PMID- 15574397
TI  - Boron remobilization at low boron supply in olive (Olea europaea) in relation to
      leaf and phloem mannitol concentrations.
AB  - For plant species in which a considerable portion of the photoassimilates are
      translocated in the phloem as sugar alcohols, boron is freely translocated from
      mature organs to growing tissues. However, the effects of decreased plant boron
      status on boron remobilization are poorly understood. We conducted a growth
      chamber experiment (CE) and a field experiment (FE) to study the effects of low
      boron supply on boron remobilization in olive (Olea europaea L.), a species that
      transports considerable amounts of mannitol in the phloem. For the CE, several
      physiological parameters were compared between control (B+) and boron-deficient
      olive plants (B-) during the expansion of new leaves. Boron remobilization was
      assessed by measuring boron content of selected leaves at the beginning and at
      the end of the CE. As expected, boron was remobilized from mature leaves to young
      leaves of B+ plants; however, considerable boron remobilization was also observed
      in B- plants, suggesting a mechanism whereby olive can sustain a minimum boron
      supply for growth of new tissues despite an insufficient external boron supply.
      Boron deficiency caused inhibition of new growth but had no effect on
      photosynthetic capacity per unit leaf surface area of young and mature leaves,
      thereby altering the carbon utilization pattern and resulting in carbon
      allocation to structures within the source leaves and accumulation of soluble
      carbohydrates. Specifically, in mature B- leaves in the CE and in B- leaves in
      the FE, mannitol concentration on a leaf water content basis increased by 48 and
      27% respectively, compared with controls. Carbon export ability (assessed by both
      phloem anatomy and phloem exudate composition of FE leaves) was enhanced at low
      boron supply. We conclude that, at low boron supply, increased mannitol
      concentrations maintain boron remobilization from source leaves to boron
      demanding sink leaves.

PMID- 15574398
TI  - Isolation and characterization of flower-specific transcripts in Acacia mangium.
AB  - Acacia mangium Willd. is a legume tree species native to subtropical and tropical
      regions of Asia and Australia. Many features of its flower development are common
      to other legume tree species. To identify genes involved in its floral
      development, we constructed a subtractive flower cDNA library against vegetative
      tissues. The 1123 expressed sequence tags (ESTs) represented 576 unique genes.
      Macroarray analysis further identified 147 of these genes as specific to the
      early, late or whole flowering process. Eight percent of these flower-specific
      genes encode MADS-domain-containing transcription factors and MYB proteins. Four
      percent encode other transcription factors and 10% encode regulatory proteins
      such as G proteins, kinases and phosphatases. Flower-specific transcripts for
      gibberellic acid (GA) synthesis and GA-induced proteins, as well as other stress-
      and pathogenesis-related genes (9%), implicate their involvement in A. mangium
      flower development. Eighteen percent of the flower-specific genes encode
      hypothetical proteins and 18% encode proteins of unknown functions. The RNA blot
      hybridization confirmed and detailed the expression patterns of selected genes.
      Functions of the A. mangium flower-specific genes are discussed based on
      comparison with their Arabidopsis homologues, most of which have been implicated
      in Arabidopsis floral development. Our work suggests general conservation of
      floral development in A. mangium and Arabidopsis. Further characterization of the
      conserved and different flower-specific genes will delineate the flowering
      process of this important legume tree species and facilitate genetic modification
      of its reproduction.

PMID- 15574399
TI  - Elevated CO2 concentration, fertilization and their interaction: growth
      stimulation in a short-rotation poplar coppice (EUROFACE).
AB  - We investigated the individual and combined effects of elevated CO2 concentration
      and fertilization on aboveground growth of three poplar species (Populus alba L.
      Clone 2AS-11, P. nigra L. Clone Jean Pourtet and P. x euramericana Clone I-214)
      growing in a short-rotation coppice culture for two growing seasons after
      coppicing. Free-air carbon dioxide enrichment (FACE) stimulated the number of
      shoots per stool, leaf area index measured with a fish-eye-type plant canopy
      analyzer (LAIoptical), and annual leaf production, but did not affect dominant
      shoot height or canopy productivity index. Comparison of LAIoptical with LAI
      estimates from litter collections and from allometric relationships showed
      considerable differences. The increase in biomass in response to FACE was caused
      by an initial stimulation of absolute and relative growth rates, which
      disappeared after the first growing season following coppicing. An ontogenetic
      decline in growth in the FACE treatment, together with strong competition inside
      the dense plantation, may have caused this decrease. Fertilization did not
      influence aboveground growth, although some FACE responses were more pronounced
      in fertilized trees. A species effect was observed for most parameters.

PMID- 15574400
TI  - Radiation-use efficiency and gas exchange responses to water and nutrient
      availability in irrigated and fertilized stands of sweetgum and sycamore.
AB  - We investigated how water and nutrient availability affect radiation-use
      efficiency (epsilon) and assessed leaf gas exchange as a possible mechanism for
      shifts in epsilon. We measured aboveground net primary production (ANPP) and
      annual photosynthetically active radiation (PAR) capture to calculate epsilon as
      well as leaf-level physiological variables (light-saturated net photosynthesis,
      Asat; stomatal conductance, gs; leaf internal CO2 concentration, Ci; foliar
      nitrogen concentration, foliar [N]; and midday leaf water potential, Psileaf)
      during the second (2001) and third (2002) growing seasons in sweetgum
      (Liquidambar styraciflua L.) and sycamore (Platanus occidentalis L.) stands
      receiving a factorial combination of irrigation and fertilization at the Savannah
      River Site, South Carolina. Irrigation and fertilization increased PAR capture
      (maximum increase 60%) in 2001 and 2002 for both species and annual PAR capture
      was well correlated with ANPP (mean r2 = 0.77). A decreasing trend in epsilon was
      observed in non-irrigated stands for sweetgum in 2001 and for sycamore in both
      years, although this was only significant for sycamore in 2002. Irrigated stands
      maintained higher gas exchange rates than non-irrigated stands for sweetgum in
      2001 and for sycamore in both years, although foliar [N] and Psileaf were
      generally unaffected. Because Ci decreased in proportion to gs in non-irrigated
      stands, it appeared that greater stomatal limitation of photosynthesis was
      associated with decreased Asat. On several measurement dates for sweetgum in 2001
      and for sycamore in both years, epsilon was positively correlated with gas
      exchange variables (Asat, gs, Ci) (r ranged from 0.600 to 0.857). These results
      indicate that PAR capture is well correlated with ANPP and that gas exchange
      rates modified by irrigation can influence the conversion of captured light
      energy to biomass.

PMID- 15574401
TI  - Variations in phenology and growth of European white birch (Betula pendula)
      clones.
AB  - Phenology can have a profound effect on growth and climatic adaptability of
      northern tree species. Although the large interannual variations in dates of bud
      burst and growth termination have been widely discussed, little is known about
      the genotypic and spatial variations in phenology and how these sources of
      variation are related to temporal variation. We measured bud burst of eight white
      birch (Betula pendula Roth) clones in two field experiments daily over 6 years,
      and determined the termination of growth for the same clones over 2 years. We
      also measured yearly height growth. We found considerable genetic variation in
      phenological characteristics among the birch clones. There was large interannual
      variation in the date of bud burst and especially in the termination of growth,
      indicating that, in addition to genetic effects, environmental factors have a
      strong influence on both bud burst and growth termination. Height growth was
      correlated with timing of growth termination, length of growth period and bud
      burst, but the relationships were weak and varied among years. We accurately
      predicted the date of bud burst from the temperature accumulation after January
      1, and base temperatures between +2 and -1 degrees C. There was large clonal
      variation in the duration of bud burst. Interannual variation in bud burst may
      have important consequences for insect herbivory of birches.

PMID- 15574402
TI  - Leaf morphology and chemistry in Fagus sylvatica (beech) trees as affected by
      site factors and ozone: results from CONECOFOR permanent monitoring plots in
      Italy.
AB  - During summer 2001, leaf samples were collected from seven beech stands that are
      part of the Italian network of permanent monitoring plots (CONECOFOR). In each
      plot, sun leaves from the upper crown were collected from five trees and
      subjected to chemical analysis (C, N, P, S, K, Ca and Mg) and morphological
      analysis (area, dry mass, thickness and thickness of individual tissues). Based
      on the measurements, nutrient ratios (N/C, N/K, N/P, N/Ca, N/Mg, K/Ca, Mg/Ca),
      sclerophylly indices (leaf mass per area (LMA) and leaf density (LD)) and
      nitrogen content per leaf area unit (NLA) were determined. Stomatal density was
      also measured. Among stands, leaf area was smallest and sclerophylly (indicated
      as LMA) was greatest in the southernmost stands and under drought conditions.
      Reduced leaf area and increased LMA also appeared to be strongly related to
      tropospheric ozone concentrations, whereas crown transparency was related mainly
      to site factors such as rainfall and temperature and, to a lesser extent, ozone
      concentration. The southernmost stands had a lower N/C ratio than the more
      northern stands, suggesting that the apoplastic fraction of cells within the leaf
      played a greater role. In the northern stands (especially at Lombardy and in
      Piedmont) where ozone concentrations were high, nutrient ratios were unbalanced
      and the high value of LMA appeared to be related primarily to the contribution of
      plasmatic components. Overall, leaf morphology was most sensitive to climate
      stress at the southern plots and to environmental pollution (nitrogen deposition
      and tropospheric ozone concentration) at some of the northern plots.

PMID- 15574403
TI  - Stem water transport of Lithocarpus edulis, an evergreen oak with radial-porous
      wood.
AB  - The stem water conducting system of an evergreen broad-leaved oak, Lithocarpus
      edulis (Mak.) Nakai, was investigated. Evergreen broad-leaved oaks (Lithocarpus,
      Castanopsis, Cyclobalanopsis, Quercus) belonging to the Quercoideae are a major
      component of Asian monsoon forests, and are characterized by the possession of
      radial-porous wood. A characteristic of radial-porous wood is the development of
      aggregate rays between radially oriented files of vessels. We measured the
      distribution of vessel lumen diameters in a stem cross section and calculated the
      theoretical water conductivity of the wood. The radial profile of the heat pulse
      velocity (HPV) was measured for an intact whole tree under field conditions and
      compared with the theoretical distribution of water conductivity. Soft X-ray
      photographs of frozen stem sections indicated that most of the vessel lumina were
      filled with water, including those of vessels more than 20 years old. Even when
      vessels were relatively wide (lumen diameters > 100 microm), cavitation was
      negligible. The rate of water uptake from the cut stem base correlated closely
      with HPV (r = 0.96), and HPV closely reflected the mean volume flow per stem
      sectional area (SFVS) around the sensor probes. However, the ray tissue sharply
      inhibited heat transfer, and the positioning of the probes strongly affected the
      absolute value of HPV. It was also found that HPV more closely reflected the mean
      sap flow velocity in the vessels than did SFVS.

PMID- 15574404
TI  - Sudden increase in atmospheric CO2 concentration reveals strong coupling between
      shoot carbon uptake and root nutrient uptake in young walnut trees.
AB  - We studied the short-term (i.e., a few days) effect of a sudden increase in CO2
      uptake by shoots on nutrient (NO3-, P ion, K+, Ca2+ and Mg2+) uptake by roots
      during vegetative growth of young walnut (Juglans nigra x J. major L.) trees. The
      increase in CO2 uptake was induced by a sudden increase in atmospheric CO2
      concentration ([CO2]). Twelve 2-year-old trees were transplanted and grown in
      perlite-filled pots in a greenhouse. Rates of CO2 uptake and water loss by
      individual trees were determined by a branch bag method from 3 days before until
      6 days after [CO2] was increased. Nutrient uptake rates were measured
      concurrently by a hydroponic recirculating nutrient solution system that provided
      non-limiting supplies of water and nutrients. Six control trees were kept in
      ambient [CO2] (360 ppm), and [CO2] was increased to 550 ppm for one set of three
      trees and to 800 ppm for another set of three trees. Before imposing the elevated
      [CO2] treatments, all trees exhibited similar daily water loss, CO2 uptake and
      nutrient uptake rates when expressed per unit leaf area to account for the tree
      size effect. Daily water loss rates were only slightly affected by elevated
      [CO2]. Carbon dioxide uptake rates greatly increased with increasing atmospheric
      [CO2], and nutrient uptake rates were proportional to CO2 uptake rates during the
      study period, except for P ion. Our results show that, despite the important
      carbon and nitrogen storage capacities previously observed in young walnut trees,
      nutrient uptake by roots is strongly coupled to carbon uptake by shoots over
      periods of a few days.

PMID- 15574405
TI  - Field measurements of ultrasonic acoustic emissions and stem diameter variations.
      New insight into the relationship between xylem tensions and embolism.
AB  - We examined interrelated xylem water tensions and embolism dynamics under field
      conditions by simultaneously monitoring ultra-acoustic emissions and changes in
      stem xylem diameter. Variation in stem xylem diameter was measured with linear
      displacement transducers to estimate variation in sap tension. Measured
      ultrasonic acoustic emissions coincided well with changes in xylem diameter,
      indicating that individual peaks in embolism occurred simultaneously with peaks
      in water tension. The good time resolution between measurements makes this method
      especially suitable for observing embolism dynamics on a short timescale. Longer
      lasting measurements can also be made to monitor inter-daily patterns in water
      tension and embolism because the techniques are non-destructive. Ultra-acoustic
      emissions occurred mainly during periods of decreasing stem xylem diameter, i.e.,
      increasing water tension, when the water tension was high enough. Embolism also
      occurred during periods of increasing xylem diameter, i.e., decreasing water
      tension, but the number of embolizing conduits under these conditions was small.

PMID- 15574406
TI  - Aluminum fractions in root tips of slash pine and loblolly pine families
      differing in Al resistance.
AB  - Aluminum (Al) distribution among several cellular fractions was investigated in
      root tips of seedlings of one Al-resistant and one Al-sensitive family of slash
      pine (Pinus elliottii Engelm.) and loblolly pine (Pinus taeda L.) grown in
      nutrient solution containing 100 microM AlCl3 (pH 4) for 167 h. Aluminum present
      in 5-mm-long root tips was fractionated into cell-wall-labile (desorbed in 0.5 mM
      citric acid), cell-wall-bound (retained after filtering disrupted cells through
      20-microm mesh) and symplasmic (filtrate following cell disruption) fractions.
      When averaged across both species, 12% of Al absorbed by root tips appeared in
      the symplasmic fraction and 88% in the apoplasmic fraction (55% as cell-wall
      labile, and 33% as cell-wall-bound). On a fresh mass basis, total Al in root tips
      was lower in loblolly pine than in slash pine, lower in the Al-resistant slash
      pine family than in the Al-sensitive slash pine family, and lower in the Al
      resistant families than in the Al-sensitive families across species. Although the
      data support the hypothesis that Al-resistant plants limit Al uptake to root
      apices, they do not exclude other mechanisms of Al resistance. Differential Al
      resistance between the species and between slash pine families may also be
      associated with the size of the total non-labile and cell-wall-labile Al
      fractions, respectively. We were unable to identify the basis for differential Al
      resistance in loblolly pine.

PMID- 15574407
TI  - Regeneration of Psychotria umbellata and production of the analgesic indole
      alkaloid umbellatine.
AB  - Psychotria umbellata Vell. (Rubiaceae), a Brazilian coastal woody species,
      produces umbellatine (also known as psychollatine), an analgesic indole alkaloid.
      An in vitro embryogenic regeneration protocol capable of yielding alkaloid
      accumulating plants was developed. Rhizogenic calli, which were obtained from
      stem segments derived from rooted apical cuttings, were cultured on Murashige and
      Skoog's (MS) medium containing either 1 mg l(-1) NAA (naphthalene acetic acid)
      and no kinetin, or 5 mg l(-1) NAA + 1 mg l(-1) kinetin. Calli did not accumulate
      umbellatine. Segments of rhizogenic callus were cultured on complete MS medium
      with various concentrations of kinetin and sucrose. Plant regeneration was best
      in the light with 0.25 mg l(-1) of kinetin and 1.5% sucrose. After 3 months of
      acclimatization in soil mixture, plant survival was 81%. Leaves of 10-month-old
      regenerated plants yielded umbellatine concentrations equivalent to those of
      adult forest-grown plants.

PMID- 15574408
TI  - Child & adolescent psychiatry: An adolescent crisis service in a rural area.

PMID- 15574409
TI  - Tyrosine 192 in apolipoprotein A-I is the major site of nitration and
      chlorination by myeloperoxidase, but only chlorination markedly impairs ABCA1
      dependent cholesterol transport.
AB  - High density lipoprotein (HDL) isolated from human atherosclerotic lesions and
      the blood of patients with established coronary artery disease contains elevated
      levels of 3-nitrotyrosine and 3-chlorotyrosine. Myeloperoxidase (MPO) is the only
      known source of 3-chlorotyrosine in humans, indicating that MPO oxidizes HDL in
      vivo. In the current studies, we used tandem mass spectrometry to identify the
      major sites of tyrosine oxidation when lipid-free apolipoprotein A-I (apoA-I),
      the major protein of HDL, was exposed to MPO or peroxynitrite (ONOO(-)). Tyrosine
      192 was the predominant site of both nitration and chlorination by MPO and was
      also the major site of nitration by ONOO(-). Electron paramagnetic spin resonance
      studies of spin-labeled apoA-I revealed that residue 192 was located in an
      unusually hydrophilic environment. Moreover, the environment of residue 192
      became much more hydrophobic when apoA-I was incorporated into discoidal HDL, and
      Tyr(192) of HDL-associated apoA-I was a poor substrate for nitration by both
      myeloperoxidase and ONOO(-), suggesting that solvent accessibility accounted in
      part for the reactivity of Tyr(192). The ability of lipid-free apoA-I to
      facilitate ATP-binding cassette transporter A1 cholesterol transport was greatly
      reduced after chlorination by MPO. Loss of activity occurred in concert with
      chlorination of Tyr(192). Both ONOO(-) and MPO nitrated Tyr(192) in high yield,
      but unlike chlorination, nitration minimally affected the ability of apoA-I to
      promote cholesterol efflux from cells. Our results indicate that Tyr(192) is the
      predominant site of nitration and chlorination when MPO or ONOO(-) oxidizes lipid
      free apoA-I but that only chlorination markedly reduces the cholesterol efflux
      activity of apoA-I. This impaired biological activity of chlorinated apoA-I
      suggests that MPO-mediated oxidation of HDL might contribute to the link between
      inflammation and cardiovascular disease.

PMID- 15574410
TI  - Interaction between the catalytic site and the A-M3 linker stabilizes E2/E2P
      conformational states of Na+,K+-ATPase.
AB  - The consequences of mutations Ile(265) --> Ala, Thr(267) --> Ala, Gly(271) -->
      Ala, and Gly(274) --> Ala for the partial reaction steps of the Na(+),K(+)-ATPase
      transport cycle were analyzed. The mutated residues are part of the long loop ("A
      M3 linker") connecting the cytoplasmic A-domain with transmembrane segment M3. It
      was found that mutation Ile(265) --> Ala displaces the E(1)-E(2) and E(1)P-E(2)P
      equilibria in favor of E(1)/E(1)P, whereas mutations Thr(267) --> Ala, Gly(271) -
      > Ala, and Gly(274) --> Ala displace these conformational equilibria in favor of
      E(2)/E(2)P. The mutations affect both the rearrangement of the cytoplasmic
      domains (seen by changes in phosphoenzyme properties and apparent ATP/vanadate
      affinities) and the membrane sector (indicated by change in K(+)/Rb(+)
      deocclusion rate). Destabilization of E(2)/E(2)P in Ile(265) --> Ala, as well as
      a direct effect on the intrinsic affinity of the E(2) form for vanadate, may be
      explained on the basis of the E(2) crystal structures of the Ca(2+)-ATPase,
      showing interaction of the equivalent isoleucine with conserved residues near the
      catalytic region of the P-domain. The rate of phosphorylation from ATP was
      unaffected in Ile(265) --> Ala, indicating a lack of interference with the
      catalytic function in E(1)/E(1)P. The effects of mutations Thr(267) --> Ala,
      Gly(271) --> Ala, and Gly(274) --> Ala provide the first evidence in the
      literature of a relative stabilization of E(2)/E(2)P resulting from perturbation
      of the A-M3 linker region. These mutations may lead to increased strain of the A
      M3 linker in E(1)/E(1)P, increased stability of the A3 helix of the A-M3 linker
      in E(2)/E(2)P, and/or a change of the orientation of the A3 helix, facilitating
      its interaction with the P-domain.

PMID- 15574411
TI  - Sendai virus RNA-dependent RNA polymerase L protein catalyzes cap methylation of
      virus-specific mRNA.
AB  - The Sendai virus (SeV) RNA-dependent RNA polymerase complex, which consists of L
      and P proteins, participates in the synthesis of viral mRNAs that possess a
      methylated cap structure. To identify the SeV protein(s) involved in mRNA cap
      methylation, we developed an in vitro assay system to detect mRNA (guanine-7
      )methyltransferase (G-7-MTase) activity. Viral ribonucleoprotein complexes and
      purified recombinant L protein but not P protein exhibited G-7-MTase activity. On
      the other hand, mRNA synthesis in a reconstituted transcription system using
      purified N-RNA (N protein-genomic RNA) complex as a template required both the L
      and P proteins. The enzymatic properties of SeV G-7-MTase were different from
      those of cellular G-7-MTase. In particular, unlike cellular G-7-MTase, the SeV
      enzyme preferentially methylated capped RNA containing the viral mRNA 5'-end
      sequences (GpppApGpG-). The C-terminal part (amino acid residues 1,756-2,228) of
      the L protein catalyzed cap methylation, whereas the N-terminal half (residues 1
      1,120) containing putative RNA polymerase subdomains did not. This is to our
      knowledge the first direct biochemical evidence that supports the idea that
      mononegavirus L protein catalyzes cap methylation as well as RNA synthesis.

PMID- 15574412
TI  - Serine 332 phosphorylation of insulin receptor substrate-1 by glycogen synthase
      kinase-3 attenuates insulin signaling.
AB  - The ability of glycogen synthase kinase-3 (GSK-3) to phosphorylate insulin
      receptor substrate-1 (IRS-1) is a potential inhibitory mechanism for insulin
      resistance in type 2 diabetes. However, the serine site(s) phosphorylated by GSK
      3 within IRS-1 had not been yet identified. Using an N-terminal deleted IRS-1
      mutant and two IRS-1 fragments, PTB-1 1-320 and PTB-2 1-350, we localized GSK-3
      phosphorylation site(s) within amino acid sequence 320-350. Mutations of serine
      332 or 336, which lie in the GSK-3 consensus motif (SXXXS) within PTB-2 or IRS-1,
      to alanine abolished their phosphorylation by GSK-3. This suggested that Ser332
      is a GSK-3 phosphorylation site and that Ser336 serves as the "priming" site
      typically required for GSK-3 action. Indeed, dephosphorylation of IRS-1 prevented
      GSK-3 phosphorylation. Furthermore, the phosphorylated peptide derived from the
      IRS-1 sequence was readily phosphorylated by GSK-3, in contrast to the
      nonphosphorylated peptide, which was not phosphorylated by the enzyme. When IRS-1
      mutants S332A(IRS-1), S336A(IRS-1), or S332A/336A(IRS-1) were expressed in
      Chinese hamster ovary cells overexpressing insulin receptors, their insulin
      induced tyrosine phosphorylation levels increased compared with that of wild-type
      (WT) IRS-1. This effect was stronger in the double mutant S332A/336A(IRS-1) and
      led to enhanced insulin-mediated activation of protein kinase B. Finally,
      immunoblot analysis with polyclonal antibody directed against IRS-1
      phosphorylated at Ser332 confirmed IRS-1 phosphorylation in cultured cells.
      Moreover, treatment with the GSK-3 inhibitor lithium reduced Ser332
      phosphorylation, whereas overexpression of GSK-3 enhanced this phosphorylation.
      In summary, our studies identify Ser332 as the GSK-3 phosphorylation target in
      IRS-1, indicating its physiological relevance and demonstrating its novel
      inhibitory role in insulin signaling.

PMID- 15574413
TI  - Efficient binding of NC2.TATA-binding protein to DNA in the absence of TATA.
AB  - Negative cofactor 2 (NC2) forms a stable complex with TATA-binding protein (TBP)
      on promoters. This prevents the assembly of transcription factor (TF) IIA and
      TFIIB and leads to repression of RNA polymerase II transcription. Here we have
      revisited the interactions of NC2.TBP with DNA. We show that NC2.TBP complexes
      exhibit a significantly reduced preference for TATA box sequences compared with
      TBP and TBP.TFIIA complexes. In chromatin immunoprecipitations, NC2 is found on a
      variety of human TATA-containing and TATA-less promoters. Substantial amounts of
      NC2 are present in a complex with TBP in bulk chromatin. A complex of NC2.TBP
      displays a K(D) for DNA of approximately 2 x 10(-9) m for a 35-bp major late
      promoter oligonucleotide. While preferentially recognizing promoter-bound TBP,
      NC2 also accelerates TBP binding to promoters and stabilizes TBP.DNA complexes.
      Our data suggest that NC2 controls TBP binding and maintenance on DNA that is
      largely independent of a canonical TATA sequence.

PMID- 15574414
TI  - Nrf2 transcriptionally activates the mafG gene through an antioxidant response
      element.
AB  - Nrf2 accumulates in nuclei upon exposure to oxidative stress, heterodimerizes
      with a small Maf protein, and activates the transcription of stress target genes
      through antioxidant response elements (AREs). We found that diethyl maleate
      (DEM), a well known activator of Nrf2, induces one of the small Maf genes, mafG.
      To elucidate roles MafG might play in the oxidative stress response, we examined
      transcriptional regulation of the mouse mafG gene. MafG utilizes three
      independent first exons that are each spliced to second and third coding exons.
      Among the small maf genes, mafG showed the strongest response to DEM, and of the
      three first exons, the highest -fold induction was seen with the proximal first
      exon (Ic). Importantly, one ARE (Ic-ARE) is conserved in the promoter flanking
      exon Ic of the human and mouse mafG genes. The Nrf2/MafG heterodimer bound the Ic
      ARE and activated transcription, whereas DEM failed to activate mafG in nrf2-null
      mutant cells. Chromatin immunoprecipitation further revealed that both Nrf2 and
      small Maf proteins associate with the Ic-ARE in vivo. These results demonstrate
      that mafG is itself an ARE-dependent gene that is regulated by an Nrf2/small Maf
      heterodimer and suggest the presence of an autoregulatory feedback pathway for
      mafG transcriptional regulation.

PMID- 15574415
TI  - Eugenol causes melanoma growth suppression through inhibition of E2F1
      transcriptional activity.
AB  - Metastatic malignant melanoma is an extremely aggressive cancer, with no
      currently viable therapy. 4-Allyl-2-methoxyphenol (eugenol) was tested for its
      ability to inhibit proliferation of melanoma cells. Eugenol but not its isomer,
      isoeugenol (2-methoxy-4-propenylphenol), was found to be a potent inhibitor of
      melanoma cell proliferation. In a B16 xenograft study, eugenol treatment produced
      a significant tumor growth delay (p = 0.0057), an almost 40% decrease in tumor
      size, and a 19% increase in the median time to end point. More significantly, 50%
      of the animals in the control group died from metastatic growth, whereas none in
      the treatment group showed any signs of invasion or metastasis. Eugenol was well
      tolerated as determined by measurement of bodyweights. Examination of the
      mechanism of the antiproliferative action of eugenol in the human malignant
      melanoma cell line, WM1205Lu, showed that it arrests cells in the S phase of the
      cell cycle. Flow cytometry coupled with biochemical analyses demonstrated that
      eugenol induced apoptosis. cDNA array analysis showed that eugenol caused
      deregulation of the E2F family of transcription factors. Transient transfection
      assays and electrophoretic mobility shift assays showed that eugenol inhibits the
      transcriptional activity of E2F1. Overexpression of E2F1 restored about 75% of
      proliferation ability in cultures. These results indicate that deregulation of
      E2F1 may be a key factor in eugenol-mediated melanoma growth inhibition both in
      vitro and in vivo. Since the E2F transcription factors provide growth impetus for
      the continuous proliferation of melanoma cells, these results suggest that
      eugenol could be developed as an E2F-targeted agent for melanoma treatment.

PMID- 15574416
TI  - Trimeric membrane-anchored gp41 inhibits HIV membrane fusion.
AB  - The HIV-1 envelope glycoprotein is composed of a receptor binding subunit, gp120
      that is non-covalently linked to the membrane-anchored fusion protein, gp41.
      Triggered by cellular receptor binding, the trimeric envelope complex mediates
      the fusion of viral and cellular membranes through the rearrangement of the
      fusion protein subunit into a six-helical bundle core structure. Here we describe
      the biophysical and functional properties of a membrane-anchored fragment of gp41
      (gp41ctm) that includes the complete C-terminal heptad repeat region 2, the
      connecting part, and the transmembrane region. We show that the transmembrane
      domain of the envelope glycoprotein is sufficient for trimerization in vitro,
      contributing most of the alpha-helical content of gp41ctm. Trimeric gp41ctm is
      protease-resistant and recognizes neutralizing antibodies 2F5 and 4E10. However,
      gp41ctm and gp41ctm proteoliposomes elicit no clear neutralizing immune responses
      in preliminary mouse studies. We further show that gp41ctm and surprisingly also
      gp41ctm proteoliposomes have potent anti-viral activity. Our data suggest that
      liposome-anchored gp41ctm exerts its inhibitory action outside of the initial
      fusion contact site, and its implications for the fusion reaction are discussed.

PMID- 15574418
TI  - Endogenous methylarginines modulate superoxide as well as nitric oxide generation
      from neuronal nitric-oxide synthase: differences in the effects of monomethyl-
      and dimethylarginines in the presence and absence of tetrahydrobiopterin.
AB  - The endogenous methylarginines asymmetric dimethylarginine (ADMA) and N(G)
      monomethyl-L-arginine (L-NMMA) regulate nitric oxide (NO) production from
      neuronal NO synthase (nNOS). Under conditions of L-arginine or
      tetrahydrobiopterin (BH(4)) depletion, nNOS also generates superoxide, O(2)(.);
      however, the effects of methylarginines on this O(2)(.) generation are poorly
      understood. Therefore, we measured the dose-dependent effects of ADMA and L-NMMA
      on the rate and amount of O(2)(.) production from nNOS under conditions of L
      arginine and/or BH(4) depletion, using electron paramagnetic resonance spin
      trapping. In the absence of L-arginine, ADMA (1 microm) inhibited O(2)(.)
      generation by approximately 60% from a rate of 56 to 23 nmol/mg/min, whereas L
      NMMA (0.1-100 microm) had no effect. L-Arginine markedly decreased the observed
      O(2)(.) adduct formation; however, O(2)(.) generation from the enzyme still
      occurs at a low rate (12.1 nmol/mg/min). This O(2)(.) leak is NOS-derived as it
      is not seen in the absence of calcium and calmodulin and demonstrates that
      O(2)(.) generation from NOS occurs even when normal substrate/ cofactor levels
      are present. Under conditions of BH(4) depletion, ADMA had no effect on O(2)(.),
      whereas L-NMMA increased O(2)(.) production almost 3-fold. This O(2)(.)
      generation was >90% inhibited by imidazole, indicating that it occurred at the
      heme center. Thus, methylarginines can profoundly shift the balance of NO and
      O(2)(.) generation from nNOS. These observations have important implications with
      regard to the therapeutic use of methylarginine-NOS inhibitors in the treatment
      of disease.

PMID- 15574417
TI  - A central role for Bid in granzyme B-induced apoptosis.
AB  - Granzyme B, a protease released from cytotoxic lymphocytes, has been proposed to
      induce target cell death by cleaving and activating the pro-apoptotic Bcl-2
      family member Bid. It has also been proposed that granzyme B can induce target
      cell death by activating caspases directly, by cleaving caspase substrates,
      and/or by cleaving several non-caspase substrates. The relative importance of Bid
      in granzyme B-induced cell death has therefore remained unclear. Here we report
      that cells isolated from various tissues of Bid-deficient mice were resistant to
      granzyme B-induced cell death. Consistent with the proposed role of Bid in
      regulating mitochondrial outer membrane permeabilization, cytochrome c remained
      in the mitochondria of Bid-deficient cells treated with granzyme B. Unlike wild
      type cells, Bid-deficient cells survived and were then able to proliferate
      normally, demonstrating the critical role for Bid in mediating granzyme B-induced
      apoptosis.

PMID- 15574419
TI  - Kinetic properties and metabolic contributions of yeast mitochondrial and
      cytosolic NADP+-specific isocitrate dehydrogenases.
AB  - To compare kinetic properties of homologous isozymes of NADP+-specific isocitrate
      dehydrogenase, histidine-tagged forms of yeast mitochondrial (IDP1) and cytosolic
      (IDP2) enzymes were expressed and purified. The isozymes were found to share
      similar apparent affinities for cofactors. However, with respect to isocitrate,
      IDP1 had an apparent Km value approximately 7-fold lower than that of IDP2,
      whereas, with respect to alpha-ketoglutarate, IDP2 had an apparent Km value
      approximately 10-fold lower than that of IDP1. Similar Km values for substrates
      and cofactors in decarboxylation and carboxylation reactions were obtained for
      IDP2, suggesting a capacity for bidirectional catalysis in vivo. Concentrations
      of isocitrate and alpha-ketoglutarate measured in extracts from the parental
      strain were found to be similar with growth on different carbon sources. For
      mutant strains lacking IDP1, IDP2, and/or the mitochondrial NAD+-specific
      isocitrate dehydrogenase (IDH), metabolite measurements indicated that major
      cellular flux is through the IDH-catalyzed reaction in glucose-grown cells and
      through the IDP2-catalyzed reaction in cells grown with a nonfermentable carbon
      source (glycerol and lactate). A substantial cellular pool of alpha-ketoglutarate
      is attributed to IDH function during glucose growth, and to both IDP1 and IDH
      function during growth on glycerol/lactate. Complementation experiments using a
      strain lacking IDH demonstrated that overexpression of IDP1 partially compensated
      for the glutamate auxotrophy associated with loss of IDH. Collectively, these
      results suggest an ancillary role for IDP1 in cellular glutamate synthesis and a
      role for IDP2 in equilibrating and maintaining cellular levels of isocitrate and
      alpha-ketoglutarate.

PMID- 15574420
TI  - A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation.
AB  - SHP2 was recently found to down-regulate PI3K activation by dephosphorylating
      Gab1 but the mechanisms explaining the positive role of the Gab1/SHP2 pathway in
      EGF-induced Ras activation remain ill defined. Substrate trapping experiments now
      suggest that SHP2 dephosphorylates other Gab1 phosphotyrosines located within a
      central region displaying four YXXP motifs. Because these sites are potential
      docking motifs for Ras-GAP, we tested whether SHP2 dephosphorylates them to
      facilitate Ras activation. We observed that a Gab1 construct preventing SHP2
      recruitment promoted membrane relocation of RasGAP. Moreover, a RasGAP-inactive
      mutant restored the activation of Ras in cells transfected with SHP2-inactivating
      Gab1 mutant or in SHP2-deficient fibroblasts, supporting the hypothesis that
      RasGAP is a downstream target of SHP2. To determine whether Gab1 is a RasGAP
      binding partner, a Gab1 mutant deleted of four YXXP motifs was produced. The
      deletion suppressed RasGAP redistribution and restored the defective Ras
      activation caused by SHP2-inactivating mutations. Moreover, Gab1 was found to
      interact with RasGAP SH2 domains, only under conditions where SHP2 is not
      activated. To identify Ras-GAP-binding sites, Tyr to Phe mutants of Gab1 YXXP
      motifs were produced. Gab1 constructs mutated on Tyr(317) were severely affected
      in RasGAP binding and were the most active in compensating for Ras-defective
      activation and blocking RasGAP redistribution induced by SHP2 inactivation. We
      have thus localized on Gab1 a Ras-negative regulatory tyrosine phosphorylation
      site involved in RasGAP binding and showed that an important SHP2 function is to
      down-regulate its phosphorylation to disengage RasGAP and sustain Ras activation.

PMID- 15574421
TI  - Repression of the human sex hormone-binding globulin gene in Sertoli cells by
      upstream stimulatory transcription factors.
AB  - Expression of the sex hormone-binding globulin gene (SHBG) in the liver produces
      SHBG, which transports sex steroids in the blood. In rodents, the SHBG gene is
      also expressed in Sertoli cells giving rise to the testicular androgen-binding
      protein, which is secreted into the seminiferous tubule where it presumably
      controls testosterone action. Evidence that the SHBG gene functions in this way
      in the human testis is lacking, and mice containing a human SHBG transgene
      (shbg4) under the control of its own promoter sequence are characterized by SHBG
      gene expression in the liver but not in the testis. A potential cis-element,
      defined as footprint 4 (FP4) within the human SHBG promoter, is absent in SHBG
      promoters of mammals that produce the testicular androgen-binding protein, and we
      have produced mice harboring a shbg4 transgene in which FP4 was deleted to
      evaluate its functional significance. Remarkably, these mice express the modified
      human SHBG transgene in the testis as well as the liver. Human SHBG transcripts
      were found within their Sertoli cells, primary cultures of which secrete human
      SHBG, and this was increased by treatment with follicle-stimulating hormone,
      retinoic acid, and estradiol but not testosterone. We have also found that the
      upstream stimulatory factors (USF-1 and USF-2) bind FP4 in vitro by
      electromobility shift assay of Sertoli cell nuclear extracts and in vivo by
      chromatin immunoprecipitation assay and conclude that USF transcription factors
      repress human SHBG transcription in Sertoli cells through an interaction with FP4
      within its proximal promoter.

PMID- 15574422
TI  - Long-term exposure to nicotine, via ras pathway, induces cyclin D1 to stimulate
      G1 cell cycle transition.
AB  - Nicotine, a major component in tobacco, has been implicated as a potential factor
      that promotes the development of lung cancer. However, the molecular mechanism of
      its action is still unclear. In this study, we have shown that, via nicotinic
      acetylcholine receptors, persistent exposure of mouse epithelial cells to
      nicotine elicits Ras signaling and subsequent Raf/MAP kinase activity,
      accompanied by a significant increase in cyclin D1 promoter activity and its
      protein expression. AP-1 is required for activation of the cyclin D1 promoter.
      The induction of cyclin D1 expression and its promoter activity by nicotine is
      abolished by the suppression of Raf/MAP kinase signaling. Furthermore, upon
      nicotine treatment, the cells do not arrest in the G(1) phase of the cell cycle
      following serum starvation. The perturbation of the G(1) cell cycle checkpoint is
      caused by the deregulation of retinoblastoma/E2F activity. Therefore, our data
      indicated that by targeting the Ras pathway, long-term exposure to nicotine
      disrupts cell cycle restriction machinery and thus potentiates tumor development.

PMID- 15574423
TI  - Involvement of the annexin II-S100A10 complex in the formation of E-cadherin
      based adherens junctions in Madin-Darby canine kidney cells.
AB  - E-cadherin and nectins are major cell-cell adhesion molecules at adherens
      junctions (AJs) in epithelial cells. When Madin-Darby canine kidney (MDCK) cells
      stably expressing nectin-1 (nectin-1-MDCK cells) are cultured at normal Ca(2+), E
      cadherin and nectin-1 are concentrated at the cell-cell contact sites. When these
      cells are cultured at low Ca(2+), E-cadherin disappears from the cell-cell
      contact sites, but nectin-1 persists there. When these cells are re-cultured at
      normal Ca(2+), E-cadherin is recruited to the nectin-based cell-cell contact
      sites. We found here that this recruitment was dependent on protein synthesis,
      because a protein synthesis inhibitor, cycloheximide, prevented the accumulation
      of E-cadherin. When nectin-1-MDCK cells, precultured at low Ca(2+) in the
      presence of a proteasome inhibitor, ALLN (N-acetyl-Leu-Leu-norleucinal), were re
      cultured at normal Ca(2+), E-cadherin was recruited to the nectin-based cell-cell
      contact sites but the level of E-cadherin was reduced. Similar results were
      obtained when wild-type MDCK cells were used instead of nectin-1-MDCK cells.
      These results suggest that degradation of one or more protein factors and de novo
      synthesis of the same or different protein factor(s) are needed for the formation
      of the E-cadherin-based AJs. We biochemically identified the annexin II-S100A10
      complex as such a candidate. Depletion of plasma membrane cholesterol, which
      abolished the localization of the annexin II-S100A10 complex at the plasma
      membrane, inhibited the re-concentration of E-cadherin at the nectin-based cell
      cell contact sites in the Ca(2+) switch experiment. Knockdown of annexin II by
      RNA interference also inhibited the re-concentration of E-cadherin. These results
      indicate that the annexin II-S100A10 complex is involved in the formation of the
      E-cadherin-based AJs in MDCK cells.

PMID- 15574425
TI  - Effect of CAT or AGG interruptions and CpG methylation on nucleosome assembly
      upon trinucleotide repeats on spinocerebellar ataxia, type 1 and fragile X
      syndrome.
AB  - Nucleosome packaging regulates many aspects of DNA metabolism and is thought to
      mediate genetic instability and transcription of expanded trinucleotide repeats.
      Both instability and transcription are sensitive to repeat length, tract purity,
      and CpG methylation. CAT or AGG interruptions within the (CAG)n or (CGG)n tracts
      of spinocerebellar ataxia, type 1 or fragile X syndrome, respectively, confer
      increased genetic stability to the repeats. We report the formation of
      nucleosomes on sequences containing pure and interrupted (CAG)n and (CGG)n
      repeats having lengths above and below the genetic stability thresholds.
      Increased lengths of pure repeats led to increased and decreased propensities for
      nucleosome assembly on the (CAG)n and (CGG)n repeats, respectively. CpG
      methylation of the CGG repeat further reduced assembly. CAT interruptions in
      (CAG)n tracts decreased nucleosome assembly. In contrast, AGG interruptions in
      (CGG)n tracts did not affect assembly by hypoacetylated histones. The latter
      observation was unaltered by CpG methylation of the repeats. However, nucleosome
      assembly by hyperacetylated histones on interrupted CGG tracts was increased
      relative to pure tracts and this effect was abolished by CpG methylation. Thus,
      CAT or AGG interruptions can modulate the ability of (CAG)n and (CGG) tracts to
      assemble into chromatin and the effect of the AGG interruptions is dependent upon
      both the methylation status of the DNA and the acetylation status of the
      histones. Compared with the genetically unstable pure repeats, both interruptions
      permit a propensity of nucleosome assembly closer to that of random (genetically
      stable) sequences, suggesting an association of nucleosome assembly of
      trinucleotide repeats and genetic instability.

PMID- 15574424
TI  - Concentrative uptake of cyclic ADP-ribose generated by BST-1+ stroma stimulates
      proliferation of human hematopoietic progenitors.
AB  - Cyclic ADP-ribose (cADPR) is an intracellular calcium mobilizer generated from
      NAD(+) by the ADP-ribosyl cyclases CD38 and BST-1. cADPR, both exogenously added
      and paracrinally produced by a CD38(+) feeder layer, has recently been
      demonstrated to stimulate the in vitro proliferation of human hemopoietic
      progenitors (HP) and also the in vivo expansion of hemopoietic stem cells. The
      low density of BST-1 expression on bone marrow (BM) stromal cells and the low
      specific activity of the enzyme made it unclear whether cADPR generation by a BST
      1(+) stroma could stimulate HP proliferation in the BM microenvironment. We
      developed and characterized two BST-1(+) stromal cell lines, expressing an
      ectocellular cyclase activity similar to that of BST-1(+) human mesenchymal stem
      cells, the precursors of BM stromal cells. Long term co-culture of cord blood
      derived HP over these BST-1(+) feeders determined their expansion. Influx of
      paracrinally generated cADPR into clonogenic HP was mediated by a concentrative,
      nitrobenzylthioinosine- and dipyridamole-inhibitable nucleoside transporter, this
      providing a possible explanation to the effectiveness of the hormone-like
      concentrations of the cyclic nucleotide measured in the medium conditioned by BST
      1(+) feeders. These results suggest that the BST-1-catalyzed generation of
      extracellular cADPR, followed by the concentrative uptake of the cyclic
      nucleotide by HP, may be physiologically relevant in normal hemopoiesis.

PMID- 15574426
TI  - Deficiency of interleukin-1 receptor antagonist deteriorates fatty liver and
      cholesterol metabolism in hypercholesterolemic mice.
AB  - Although the anti-inflammatory effect of interleukin-1 (IL-1) receptor antagonist
      (IL-1Ra) has been described, the contribution of this cytokine to cholesterol
      metabolism remains unclear. Our aim was to ascertain whether deficiency of IL-1Ra
      deteriorates cholesterol metabolism upon consumption of an atherogenic diet. IL
      1Ra-deficient mice (IL-1Ra(-/-)) showed severe fatty liver and portal fibrosis
      containing many inflammatory cells following 20 weeks of an atherogenic diet when
      compared with wild type (WT) mice. Expectedly, the levels of total cholesterol in
      IL-1Ra(-/-) mice were significantly increased, and the start of lipid
      accumulation in liver was observed earlier when compared with WT mice. Real-time
      PCR analysis revealed that IL-1Ra(-/-) mice failed to induce mRNA expression of
      cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid
      synthesis, with concurrent up-regulation of small heterodimer partner 1 mRNA
      expression. Indeed, IL-1Ra(-/-) mice showed markedly decreased bile acid
      excretion, which is elevated in WT mice to maintain cholesterol level under
      atherogenic diet feeding. Therefore, we conclude that the lack of IL-1Ra
      deteriorates cholesterol homeostasis under atherogenic diet-induced inflammation.

PMID- 15574427
TI  - Distal substrate interactions enhance plasmepsin activity.
AB  - Plasmepsin II (PM II) is an aspartic protease active in hemoglobin (Hb)
      degradation in the protozoan parasite Plasmodium falciparum. A fluorescence
      quenched octapeptide substrate based on the initial hemoglobin cleavage site is
      recognized well by PM II. C-terminal extension of this peptide has little effect,
      but N-terminal extension results in higher maximal velocity and dramatic
      concentration-dependent substrate inhibition. This inhibition, but not the rate
      stimulation, depends on the presence of a DABCYL group on the peptide N terminus.
      Using site-directed mutagenesis, we have identified PM II residues that interact
      with N-terminal amino acids of peptide substrates. The same residues influence
      degradation of Hb by PM II. Cathepsin E (CatE), a related mammalian aspartic
      protease, is also stimulated by N-terminally extended substrates. This suggests
      that distal substrate interactions as far out as P6 may be a general property of
      aspartic proteases and may be important in substrate and inhibitor recognition.
      Although PM II and CatE are similar in their ability to cleave Hb-based peptides
      and Hb alpha-chains, CatE is not able to degrade native Hb, which is a substrate
      for PM II. Based on these results, we propose that PM II may have the special
      feature of being a Hb denaturase.

PMID- 15574428
TI  - The cytosolic domains of Ca2+-sensitive adenylyl cyclases dictate their targeting
      to plasma membrane lipid rafts.
AB  - Lipid rafts are specialized, cholesterol-rich domains of the plasma membrane that
      are enriched in certain signaling proteins, including Ca(2+)-sensitive adenylyl
      cyclases. This restrictive localization plays a key role in the regulation of the
      Ca(2+)-stimulable AC8 and the Ca(2+)-inhibitable AC6 by capacitative calcium
      entry. Interestingly, AC7, a Ca(2+)-insensitive AC, is found in the plasma
      membrane but is excluded from lipid rafts (Smith, K. E., Gu, C., Fagan, K. A.,
      Hu, B., and Cooper, D. M. F. (2002) J. Biol. Chem. 277, 6025-6031). The
      mechanisms governing the specific membrane targeting of adenylyl cyclase isoforms
      remain unknown. To address this issue, a series of chimeras were produced between
      the raft-targeted AC5 and the non-raft-targeted AC7, involving switching of their
      major domains. The AC5-AC7 chimeras were expressed in HEK 293 cells and lipid
      rafts were isolated from the bulk plasma membrane by either detergent-based or
      non-detergent-based fractionation methods. Additionally, confocal imaging was
      used to investigate the precise cellular targeting of the chimeras. Surprisingly,
      the two tandem six-transmembrane domains of AC5 were not required for
      localization to lipid rafts. Rather, AC5 localization depended on the complete
      cytoplasmic loops (C1 and C2); constructs with mixed domains were either retained
      in the endoplasmic reticulum or degraded. Similar conclusions are drawn for the
      lipid raft localization of the Ca(2+)/calmodulin-stimulable AC8; again, the C1
      and C2 domains are critical. Thus, protein-protein interactions may be more
      important than protein-lipid interactions in targeting these calcium-sensitive
      enzymes to lipid rafts.

PMID- 15574429
TI  - FLT3/ITD mutation signaling includes suppression of SHP-1.
AB  - Mutations in the FLT3 gene are the most common genetic alteration found in AML
      patients. FLT3 internal tandem duplication (ITD) mutations result in constitutive
      activation of FLT3 tyrosine kinase activity. The consequences of this activation
      are an increase in total phosphotyrosine content, persistent downstream
      signaling, and ultimately transformation of hematopoietic cells to factor
      independent growth. The Src homology (SH)2 domain-containing protein-tyrosine
      phosphatase (SHP)-1 is involved in the down-regulation of a broad range of growth
      factor and cytokine-driven signaling cascades. Loss-of-function or deficiency of
      SHP-1 activity results in a hyperproliferative response of myelomonocytic cell
      populations to growth factor stimulation. In this study, we examined the possible
      role of SHP-1 in regulating FLT3 signaling. We found that transformation of TF-1
      cells with FLT3/ITD mutations suppressed the activity of SHP-1 by approximately 3
      fold. Suppression was caused by decreased SHP-1 protein expression, as analyzed
      at both the protein and RNA levels. In contrast, protein levels of SHP-2, a
      phosphatase that plays a stimulatory role in signaling through a variety of
      receptors, did not change significantly in FLT3 mutant cells. Suppressed SHP-1
      protein levels in TF-1/ITD cells were partially overcome after cells were exposed
      to CEP-701, a selective FLT3 inhibitor. SHP-1 protein levels also increased in
      naturally occurring FLT3/ITD expressing AML cell lines and in primary FLT3/ITD
      AML samples after CEP-701 treatment. Furthermore, a small but reproducible
      growth/survival advantage was observed in both TF-1 and TF-1/ITD cells when SHP-1
      expression was knocked down by RNAi. Taken together, these data provide the first
      evidence that suppression of SHP-1 by FLT3/ITD signaling may be another mechanism
      contributing to the transformation by FLT3/ITD mutations.

PMID- 15574430
TI  - Interleukin-18 is a pro-hypertrophic cytokine that acts through a
      phosphatidylinositol 3-kinase-phosphoinositide-dependent kinase-1-Akt-GATA4
      signaling pathway in cardiomyocytes.
AB  - In patients with congestive heart failure, high serum levels of the
      proinflammatory cytokine interleukin (IL)-18 were reported. A positive
      correlation was described between serum IL-18 levels and the disease severity. IL
      18 has also been shown to induce atrial natriuretic factor (ANF) gene expression
      in adult cardiomyocytes. Because re-expression of the fetal gene ANF is mostly
      associated with hypertrophy, a hallmark of heart failure, we hypothesized that IL
      18 induces cardiomyocyte hypertrophy. Treatment of the cardiomyocyte cell line HL
      1 with IL-18 induced hypertrophy as characterized by increases in protein
      synthesis, phosphorylated p70 S6 kinase, and ribosomal S6 protein levels as well
      as cell surface area. Furthermore, IL-18 induced ANF gene transcription in a time
      dependent manner as evidenced by increased ANF secretion and ANF promoter-driven
      reporter gene activity. Investigation into possible signal transduction pathways
      mediating IL-18 effects revealed that IL-18 activates phosphoinositide 3-kinase
      (PI3K), an effect that was blocked by wortmannin and LY-294002. IL-18 induced Akt
      phosphorylation and stimulated its activity, effects that were abolished by Akt
      inhibitor or knockdown. IL-18 stimulated GATA4 DNA binding activity and increased
      transcription of a reporter gene driven by multimerized GATA4-binding DNA
      elements. Pharmacological inhibition or knockdown studies revealed that IL-18
      induced cardiomyocyte hypertrophy and ANF gene transcription via PI3K, PDK1, Akt,
      and GATA4. Most importantly, IL-18 induced ANF gene transcription and hypertrophy
      of neonatal rat ventricular myocytes via PI3K-, Akt-, and GATA4-dependent
      signaling. Together these data provide the first evidence that IL-18 induces
      cardiomyocyte hypertrophy via PI3K-dependent signaling, defines a mechanism of IL
      18-mediated ANF gene transcription, and further supports a role for IL-18 in
      inflammatory heart diseases including heart failure.

PMID- 15574431
TI  - Structural and biochemical characterization of CIB1 delineates a new family of EF
      hand-containing proteins.
AB  - CIB1 (CIB) is an EF-hand-containing protein that binds multiple effector
      proteins, including the platelet alphaIIbbeta3 integrin and several
      serine/threonine kinases and potentially modulates their function. The crystal
      structure for Ca(2+)-bound CIB1 has been determined at 2.0 A resolution and
      reveals a compact alpha-helical protein containing four EF-hands, the last two of
      which bind calcium ions in the standard fashion seen in many other EF-hand
      proteins. CIB1 shares high structural similarity with calcineurin B and the
      neuronal calcium sensor (NCS) family of EF-hand-containing proteins. Most
      importantly, like calcineurin B and NCS proteins, which possess a large
      hydrophobic pocket necessary for ligand binding, CIB1 contains a hydrophobic
      pocket that has been implicated in ligand binding by previous mutational
      analysis. However, unlike several NCS proteins, Ca(2+)-bound CIB1 is largely
      monomeric whether bound to a relevant peptide ligand or ligand-free. Differences
      in structure, oligomeric state, and phylogeny define a new family of CIB1-related
      proteins that extends from arthropods to humans.

PMID- 15574432
TI  - Convergent evolution of a 2-methylbutyryl-CoA dehydrogenase from isovaleryl-CoA
      dehydrogenase in Solanum tuberosum.
AB  - The potato cDNAs Solanum tuberosum isovaleryl-CoA dehydrogenases 1 and 2 (St-IVD1
      and St-IVD2) encode proteins that are 84% identical to each other and 65 and 64%
      identical to human IVD, respectively. St-IVD2 protein was previously partially
      purified from potato tubers and confirmed to be an IVD. The function of St-IVD1
      is unknown. In these experiments, both proteins were expressed in Escherichia
      coli and purified as intact homotetramers. The substrate preference profile of
      the St-IVD2 protein was similar to that of human IVD. However, recombinant St
      IVD1 had maximal activity with 2-methylbutyryl-CoA, which in humans is
      dehydrogenated by short/branched-chain acyl-CoA dehydrogenase (SBCAD). Whereas
      molecular modeling predicts that the 2-methylbutyryl-CoA dehydrogenase (2MBCD)
      and IVD substrate binding pockets are nearly identical, 2MBCD has amino acid
      substitutions at five residues that are invariant among all of the known and
      putative IVDs. Site-directed mutagenesis was used to match the human IVD active
      site with that of potato 2MBCD. The resulting mutant IVD had detectable activity
      with 2-methylbutyryl-CoA and no activity with isovaleryl-CoA. The 2MBCD active
      site was compared with that of human SBCAD using molecular modeling. Residues Met
      361 and Ala-365 of 2MBCD appear to partially substitute for the function of Tyr
      380 in human SBCAD, binding the methyl branch linked to C2 of 2-methylbutyryl
      CoA, whereas residues Val-88, Val-92, and Val-96 appear to bind the distal C4
      methyl group. The presence of a 2MBCD in potato that is highly homologous to IVD
      is an example of convergent evolution within the acyl-CoA dehydrogenase family,
      leading to the independent occurrence of two enzymes (SBCAD and 2MBCD) specific
      for 2-methylbutyryl-CoA.

PMID- 15574433
TI  - Letting Charlotte die.

PMID- 15574434
TI  - Free speech, democracy, and eugenics.

PMID- 15574435
TI  - Surveys on attitudes towards legalisation of euthanasia: importance of question
      phrasing.
AB  - AIM: To explore whether the phrasing of the questions and the response
      alternatives would influence the answers to questions about legalisation of
      euthanasia. METHODS: Results were compared from two different surveys in
      populations with similar characteristics. The alternatives "positive",
      "negative", and "don't know" (first questionnaire) were replaced with an
      explanatory text, "no legal sanction", four types of legal sanctions, and no
      possibility to answer "don't know" (second questionnaire). Four undergraduate
      student groups (engineering, law, medicine, and nursing) answered. RESULTS: In
      the first questionnaire (n = 684) 43% accepted euthanasia (range 28-50%), 14% (8
      33%) did not, and 43% (39-59%) answered "don't know". Two per cent of the
      respondents declined to answer. In comparison with previous surveys on attitudes
      to euthanasia the proportion of "don't know" was large. The results of the second
      questionnaire (n = 639), showed that 38% favoured "no legal prosecution" (26
      50%). However, 62% (50-74%) opted for different kinds of legal sanctions, and two
      of four groups expressed significantly different views in the two surveys. A
      proportion of 10% declined to answer the second questionnaire. CONCLUSION: An
      introduction of an explanatory text and a wider range of response alternatives
      produced differences between the results of the two surveys conducted.

PMID- 15574436
TI  - Cell phoney: human cloning after Quintavalle.
AB  - Reproductive cloning has thrown up new scientific possibilities, ethical
      conundrums, and legal challenges. An initial question, considered by the English
      courts in 2003, was whether the technique presently available, that of cell
      nucleus replacement, falls outside the provisions of the Human Fertilisation and
      Embryology Act 1990. If it does, the creation and use, including use in research
      protocols, of human embryos would be unregulated, disclosing a need to consider
      remedial legislation. The resolution by the courts of this legal question
      dramatically engages them in a resolution of fundamental ethical dilemmas, and
      discloses the possibilities and limitation of negotiating science policy through
      the processes of litigation.

PMID- 15574437
TI  - Reproductive and therapeutic cloning, germline therapy, and purchase of gametes
      and embryos: comments on Canadian legislation governing reproduction
      technologies.
AB  - In Canada, the Assisted Human Reproduction Act received royal assent on 29 March
      2004. The approach proposed by the federal government responds to Canadians'
      strong desire for an enforceable legislative framework in the field of
      reproduction technologies through criminal law. As a result of the widening gap
      between the rapid pace of technological change and governing legislation, a
      distinct need was perceived to create a regulatory framework to guide decisions
      regarding reproductive technologies. In this article the three main topics
      covered in the new legislation are commented on: cloning, germline therapy, and
      purchase of gametes and embryos. Some important issues also covered in the new
      legislation, such as privacy and access to information, data protection, identity
      of donors, and inspection, will not be addressed.

PMID- 15574438
TI  - Should selecting saviour siblings be banned?
AB  - By using tissue typing in conjunction with preimplantation genetic diagnosis
      doctors are able to pick a human embryo for implantation which, if all goes well,
      will become a "saviour sibling", a brother or sister capable of donating life
      saving tissue to an existing child. This paper addresses the question of whether
      this form of selection should be banned and concludes that it should not. Three
      main prohibitionist arguments are considered and found wanting: (a) the claim
      that saviour siblings would be treated as commodities; (b) a slippery slope
      argument, which suggests that this practice will lead to the creation of so
      called "designer babies"; and (c) a child welfare argument, according to which
      saviour siblings will be physically and/or psychologically harmed.

PMID- 15574439
TI  - Commodification of children again and non-disclosure preimplantation genetic
      diagnosis for Huntington's disease.

PMID- 15574440
TI  - Doctors' views about the importance of shared values in HIV positive patient
      care: a qualitative study.
AB  - Robert Veatch has proposed a model of the doctor-patient relationship that has as
      its foundation the sharing of values between the doctor and the patient. This
      paper uses qualitative research conducted with six doctors involved in the long
      term, specialised care of HIV positive patients in South Australia to explore the
      practical application of Veatch's value sharing model in that setting. The
      research found that the doctors in this study linked "values" with sexual
      identity such that they defined value sharing, in part, as a shared set of values
      and beliefs about sexual identity and practices. They voluntarily identified
      themselves as either homosexual or heterosexual and they regarded the relation
      between their own sexual identity and that of their patients as important for the
      provision of quality care. None of the doctors thought that value sharing, in the
      way they defined it, was essential to the clinical relationship, but the
      homosexual doctors attributed a greater degree of importance to it than their
      heterosexual colleagues.

PMID- 15574441
TI  - Willingness to donate: an interview study before liver transplantation.
AB  - OBJECTIVES: The introduction of the living donation in organ transplantation
      introduces important new psychological conflicts and ethical questions in the
      transplantation process. Operation related risks, as well as dependencies in the
      family structure, generate considerable pressure on potential donors. The aim of
      the study was to reconstruct the determinants of willingness to donate before
      transplantation. METHODS: Evaluation of 20 taped and transcribed interviews
      oriented to current approaches in qualitative interview research. The approach
      used is based on grounded theory, qualitative content analysis, and the concept
      of the ideal type. RESULTS: Before surgery, "openly motivated" donors push for an
      operation, leaving no room for ambivalence in the evaluation process. They
      idealise the relationship with the recipient, and link their donation with the
      individual-partly in subconscious expectations and wishes. In contrast, "openly
      ambivalent" donors formulate their anxieties and express arguments against
      donation. CONCLUSIONS: Statements that claim ambivalence towards donation or
      utterance of arguments against donation indicate earlier coercion. Before
      transplantation, potential donors should have the opportunity to discuss their
      emotional situation to help their decision making process.

PMID- 15574443
TI  - Rights of patients in developing countries: the case of Turkey.
AB  - Patient rights are universal values which we have to adopt. It is not so easy,
      however, to put such values and principles into effect. As approaches and
      attitudes differ from individual to individual, from society to society, and from
      country to country, a uniform application of these values is difficult. If we
      want to reach a general conclusion about the status of patient rights in the
      world as whole, we should examine the situation in individual countries. As far
      as Turkey is concerned, we can say that, although the idea of patient rights is
      accepted in principle, patient rights have yet to be adequately implemented.

PMID- 15574442
TI  - The ethics of the placebo in clinical practice.
AB  - While discussions of the ethics of the placebo have usually dealt with their use
      in a research context, the authors address here the question of the placebo in
      clinical practice. It is argued, firstly, that the placebo can be an effective
      treatment. Secondly, it is demonstrated that its use does not always entail
      deception. Finally guidelines are presented according to which the placebo may be
      used for clinical purposes. It is suggested that in select cases, use of the
      placebo may even be morally imperative. The argument is illustrated by three case
      vignettes.

PMID- 15574444
TI  - Bioterrorism and smallpox planning: information and voluntary vaccination.
AB  - Although smallpox was declared eradicated in 1980, there are fears that stocks of
      the virus manufactured for military purposes by the Soviet Union may have fallen
      into the hands of "rogue nations" or terrorists. Worries about bioterrorism have
      thus sparked debate about whether or not the smallpox vaccine, which can be
      dangerous, should be offered to the general public. Meaningful public debate on
      this issue requires expert information about the likelihood that the virus will
      in fact be used as a weapon. Informed voluntary individual decision making, about
      whether to get vaccinated if vaccine is made available to the public, would
      similarly require appreciation of the likelihood of attack. Public deliberation
      and private deliberation thus both require briefing by the intelligence
      community.

PMID- 15574445
TI  - Obtaining explicit consent for the use of archival tissue samples: practical
      issues.
AB  - BACKGROUND: Over the past few years, research ethics committees have increasingly
      demanded explicit consent before archival tissue samples can be used in research
      projects. Current UK guidance in this area requires an assessment of whether it
      is "practical" to obtain explicit consent. Ethics committees have little
      experience or evidence to help them to judge what is "practical" in this context.
      METHODS: We attempted to obtain general consent for research use of surplus
      tissue from renal transplant biopsies from the entire patient population of the
      renal transplant unit in Leicester. The nature of this patient population would
      be expected to facilitate this task. RESULTS: A total of 495 letters were sent.
      Attempts were made to contact non-responders when they attended the outpatient
      clinic. One year after the initiation of the project, the opinions of 26% of the
      patients had still not been ascertained. CONCLUSIONS: The results confirm that
      the vast majority of patients are happy for "surplus" biopsy material to be used
      for research; the situation does not parallel the use of autopsy tissue. A
      requirement to obtain explicit consent for the study of archival tissue is
      likely, however, to block or at least seriously delay research, which is contrary
      to the public interest and specifically may harm the interests of the patients
      concerned. In the UK, the problem of tissue being used against the wishes of the
      donor has now been largely replaced by the problem of prohibition of tissue use
      against the wishes of the donor.

PMID- 15574446
TI  - The battering of informed consent.
AB  - Autonomy has been hailed as the foremost principle of bioethics, and yet
      patients' decisions and research subjects' voluntary participation are being
      subjected to frequent restrictions. It has been argued that patient care is best
      served by a limited form of paternalism because the doctor is better qualified to
      take critical decisions than the patient, who is distracted by illness. The
      revival of paternalism is unwarranted on two grounds: firstly, because prejudging
      that the sick are not fully autonomous is a biased and unsubstantial view;
      secondly, because the technical knowledge of healthcare professionals does not
      include the ethical qualifications and prerogative to decide for others.Clinical
      research settings are even more prone to erode subjects' autonomy than clinical
      settings because of the tendency and temptation to resort to such practices as
      shading the truth when consent to participation is sought, or waiving consent
      altogether when research is done in emergency settings. Instead of supporting
      such dubious practices with unconvincing arguments, it would seem to be the task
      of bioethics to insist on reinforcing autonomy.

PMID- 15574448
TI  - The public autopsy: somewhere between art, education, and entertainment.

PMID- 15574447
TI  - Is there an Aboriginal bioethic?
AB  - It is well recognised that medicine manifests social and cultural values and that
      the institution of healthcare cannot be structurally disengaged from the
      sociopolitical processes that create such values. As with many other indigenous
      peoples, Aboriginal Australians have a lower heath status than the rest of the
      community and frequently experience the effects of prejudice and racism in many
      aspects of their lives. In this paper the authors highlight values and ethical
      convictions that may be held by Aboriginal peoples in order to explore how health
      practitioners can engage Aboriginal patients in a manner that is more
      appropriate. In doing so the authors consider how the ethics, values, and beliefs
      of the dominant white Australian culture have framed the treatment and delivery
      of services that Aboriginal people receive, and whether sufficient effort has
      been made to understand or acknowledge the different ethical predispositions that
      form the traditions and identity of Aboriginal Australia(ns).

PMID- 15574449
TI  - Attitudes of healthcare professionals and parents regarding genetic testing for
      violent traits in childhood.
AB  - OBJECTIVES: Although no genetic tests for violent behaviour are currently
      available, research is ongoing to isolate genes related to a propensity for
      violence. We explored the attitudes of parents and healthcare professionals
      toward behavioural genetic testing for violence. DESIGN: The attitudes of
      healthcare professionals and the lay public about genetic testing of children
      were elicited for a range of conditions through interviews with healthcare
      professionals and focus groups with parents. All participants were informed that
      behavioural genetic testing was the only hypothetical genetic test in our script
      and it was presented as the last condition. PARTICIPANTS: The healthcare
      professionals included both genetic professionals and paediatricians. Focus group
      participants were recruited through various community institutions in the
      southside of Chicago and nearby suburbs. RESULTS: The healthcare professionals
      tended to medicalise behavioural genetics, and were opposed to testing unless
      treatment was available. They were also uniformly concerned about the potential
      harms of this information, including unintentional adverse effects from
      environmental changes. In contrast, parents wanted genetic testing for
      behavioural traits to be available even in the absence of proved medical
      treatments. Not all parents wanted to test their own children, and some parents
      were concerned about self-fulfilling prophecies. Some parents, however, felt the
      information was important for their understanding, and could be used to support
      environmental changes. CONCLUSIONS: While healthcare professionals medicalised
      behavioural genetics, parents focused on environmental causes and influences.
      Consequently, healthcare professionals do not want to offer testing if there is
      no clear treatment, while parents may want this information to shape
      environmental influences.

PMID- 15574450
TI  - Genes and equality.
AB  - The way people think about equality as a value will influence how they think
      genetic interventions should be regulated. In this paper the author uses the
      taxonomy of equality put forth by Derek Parfit and applies this to the issue of
      genetic interventions. It is argued that telic egalitarianism is untenable and
      that deontic egalitarianism collapses into prioritarianism. The priority view
      maintains that it is morally more important to benefit the people who are worse
      off. Once this precision has been given to the concerns egalitarians have, a
      number of diverse issues must be considered before determining what the just
      regulation of genetic interventions would be. Consideration must be given to the
      current situation of the least advantaged, the fiscal realities behind genetic
      interventions, the budget constraints on other social programmes egalitarians
      believe should receive scarce public funds, and the interconnected nature of
      genetic information. These considerations might lead egalitarians to abandon what
      they take to be the obvious policy recommendations for them to endorse regarding
      the regulation of gene therapies and enhancements.

PMID- 15574451
TI  - The person, the soul, and genetic engineering.
AB  - Argument about the ethical possibility of the therapeutic use of embryonic stem
      cells depends critically on the evaluation of the moral status of the very early
      embryo. Some assert that at the blastocyst stage it is only potentially human,
      not yet possessing the full ethical status of personhood, while others assert
      that from its formation the embryo possesses all the moral rights of a human
      person. It is shown that a decision on this issue is closely related to how human
      nature is to be understood. The idea of a person as a dual combination of body
      and spirit correlates naturally with the assertion of absolute personhood from
      conception, while an idea of human psychosomatic unity encourages a development
      picture in which the embryo only grows gradually into personhood. The latter view
      is seen to be encouraged by new advances in science which emphasise the
      importance of the concept of information in the discussion of complex systems.
      Other ethical issues related to human genetics are also briefly reviewed.

PMID- 15574453
TI  - Presenting behavioural genetics: spin, ideology, and our narrative interests.
AB  - A short review is given of the Nuffield Council's report on behavioural genetics.
      This review is used as an entry point to a discussion of the factors that
      influence the presentation of behavioural genetics in the media and in the
      popular scientific press. It is argued that our interest in formulating narrative
      explanations of our individual lives puts pressure on publishers and editors to
      present behavioural genetics in a selective, misleading, way. Some other
      influences on presentation are discussed and it is suggested that the Nuffield
      report is particularly useful in so far as it lacks these distorting influences.

PMID- 15574454
TI  - The Roman Catholic Church and embryonic stem cells.

PMID- 15574455
TI  - Non-compliance: a side effect of drug information leaflets.

PMID- 15574456
TI  - Response to "Patient organisations should also establish databanks on medical
      complications".

PMID- 15574457
TI  - Symposium on consent and confidentiality. J Med Ethics 2003;29:2-40.

PMID- 15574458
TI  - What do patients value in their hospital care? A response to Joffe et al.

PMID- 15574460
TI  - How to be a "good" medical student.

PMID- 15574461
TI  - Ferrochelatase consisting of wild-type and mutated subunits from patients with a
      dominant-inherited disease, erythropoietic protoporphyria, is an active but
      unstable dimer.
AB  - Erythropoietic protoporphyria (EPP) is an autosomal inherited disease of heme
      biosynthesis caused by a partial deficiency of the enzyme ferrochelatase.
      Patients with EPP show only 20-30% normal activity because of mutations in one of
      the alleles of the ferrochelatase gene. To clarify the molecular mechanisms of
      this low level of activity, we co-expressed human ferrochelatase carrying His-
      and HA-tags in a tandem fashion in Escherichia coli. Purification of the His-tag
      containing enzyme revealed that the His-enzyme forms an oligomer in association
      with the HA-enzyme, and analysis by gel-filtration confirmed that the enzyme is a
      dimer (approximately 80 kDa). Then we expressed homo- and heterodimers composed
      of the wild-type and engineered mutants of the enzyme (C395Delta, H157A, H263A,
      H388A) or mutants from EPP patients (I186T, M267I). The levels of homodimeric
      enzymes produced were low, and the activities of the purified homodimeric mutants
      were abolished. On the other hand, the heterodimers with wild-type and mutated
      subunits exhibited potential, but weak, activities without a marked change of Km
      values for substrates. These results showed that heterodimers containing normal
      and mutated subunits retain the enzymic activity, which is inconsistent with the
      hypothesis that ferrochelatase is only active when the dimer contains two normal
      subunits. Pretreatment at 42 degrees C led to a rapid inactivation of the
      heterodimeric mutants, indicating instability. Thus, we provide evidence that the
      instability of the heterodimer containing normal and mutated ferrochelatase as
      well as the low production levels due to the structural defect of the mutant
      protein, not the abolishment of the enzymic activity of the heterodimer, causes
      the weak activity in EPP patients.

PMID- 15574462
TI  - Differential DNA hypermethylation and hypomethylation signatures in colorectal
      cancer.
AB  - Cancer cells are characterized by a generalized disruption of the DNA methylation
      pattern involving an overall decrease in the level of 5-methylcytosine together
      with regional hypermethylation of particular CpG islands. The extent of both DNA
      hypomethylation and hypermethylation in the tumor cell is likely to reflect
      distinctive biological and clinical features, although no studies have addressed
      its concurrent analysis until now. DNA methylation profiles in sporadic
      colorectal carcinomas, synchronous adenoma-carcinoma pairs and their matching
      normal mucosa were analyzed by using the amplification of inter-methylated sites
      (AIMS) method. A total of 208 AIMS generated sequences were tagged and evaluated
      for differential methylation. Global indices of hypermethylation and
      hypomethylation were calculated. All tumors displayed altered patterns of DNA
      methylation in reference to normal tissue. On average, 24% of the tagged
      sequences were differentially methylated in the tumor in regard to the normal
      pair with an overall prevalence of hypomethylations to hypermethylations.
      Carcinomas exhibited higher levels of hypermethylation than did adenomas but
      similar levels of hypomethylation. Indices of hypomethylation and
      hypermethylation showed independent correlations with patient's sex, tumor
      staging and specific gene hypermethylation. Hierarchical cluster analysis
      revealed two main patterns of DNA methylation that were associated to particular
      mutational spectra in the K-ras and the p53 genes and alternative correlates of
      hypomethylation and hypermethylation with survival. We conclude that DNA
      hypermethylation and hypomethylation are independent processes and appear to play
      different roles in colorectal tumor progression. Subgroups of colorectal tumors
      show specific genetic and epigenetic signatures and display distinctive
      correlates with overall survival.

PMID- 15574463
TI  - Identification and functional consequences of a novel MRE11 mutation affecting 10
      Saudi Arabian patients with the ataxia telangiectasia-like disorder.
AB  - Ten new patients with ataxia telangiectasia-like disorder (ATLD) from three
      unrelated Saudi Arabian families have been identified aged 5-37 representing the
      largest cohort of ATLD patients ever identified. They presented with an early
      onset, slowly progressive, ataxia plus ocular apraxia phenotype with an absence
      of tumor development, even in the oldest patient. Extra-neurological features
      such as telangiectasia, raised alpha-fetoprotein and reduced immunoglobulin
      levels were absent. No translocations were found in the two investigated
      patients, and the presence of microcephaly was noted in four out of eight
      ascertained patients. All patients are homozygous for a novel missense mutation
      (630G-->C, W210C) of the MRE11 gene. The cellular consequences of this amino acid
      change, localized in the nuclease domain of the Mre11 protein, have been
      determined in fibroblast cultures established from two individuals. They showed
      high constitutive levels of Mre11 and Rad50 proteins compared with cells from
      normal individuals but a very low level of the Nbs1 protein. After exposure to
      ionizing radiation, a dose-dependent defect in ataxia telangiectasia mutated
      (ATM)-serine 1981, p53-serine 15 and Chk2 phosphorylation, and p53 stabilization
      were noted, together with a failure to form Mre11 foci and enhanced radiation
      sensitivity. Formation of gammaH2AX foci was similar to that seen in normal
      fibroblasts under the experimental conditions examined. These results emphasize
      the importance of functional interactions among the three proteins of the Mre11
      Rad50-Nbs1 complex and lend support to a role of this complex as a sensor of DNA
      double-strand breaks, acting upstream of ATM.

PMID- 15574464
TI  - Fukutin-related protein mutations that cause congenital muscular dystrophy result
      in ER-retention of the mutant protein in cultured cells.
AB  - Mutations in the gene encoding fukutin-related protein (FKRP) cause a spectrum of
      diseases including congenital muscular dystrophy type 1C (MDC1C), limb girdle
      muscular dystrophy 2I (LGMD2I) and congenital muscular dystrophies (CMDs) with
      brain malformations and mental retardation. Although these diseases are
      associated with abnormal dystroglycan processing, the cellular consequences of
      the idiosyncratic FKRP mutations have not been determined. Here we show, in
      cultured cells, that FKRP mutants associated with the more severe disease
      phenotypes (S221R, A455D, P448L) are retained in the endoplasmic reticulum (ER),
      whereas the wild-type protein and the mutant L276I that causes LGMD2I are found
      predominantly in the Golgi apparatus. The ER-retained proteins have a shorter
      half-life than the wild-type FKRP and are preferentially degraded by the
      proteasome. Furthermore, calnexin binds preferentially to the ER-retained mutants
      suggesting that it may participate in the quality control pathway for FKRP. These
      data provide the first evidence that the ER-retention of mutant FKRP may play a
      role in the pathogenesis of CMD and potentially explain why the allelic disorder
      LGMD2I is milder, because the mutated protein is able to reach the Golgi
      apparatus.

PMID- 15574465
TI  - Cancer risk in people with epilepsy: the role of antiepileptic drugs.
AB  - There has been considerable debate about the relationship between epilepsy and
      cancer, in particular whether the incidence of cancer is increased in people with
      epilepsy and whether antiepileptic drugs promote or protect against cancer. We
      review available evidence from animal experiments, genotoxicity studies and
      clinico-epidemiological observations, and discuss proposed mechanisms underlying
      the association between epilepsy and cancer. A carcinoma-promoting effect has
      been seen unequivocally in rodent models for phenobarbital and phenytoin;
      phenobarbital promoted liver tumours and phenytoin caused lymphoid cell and liver
      tumours in rats. Early human epidemiological studies found an association between
      phenobarbital and hepatocellular carcinoma, and several subsequent studies
      suggested an association with lung cancer. An association with brain tumours has
      also been demonstrated. Phenytoin has been causally implicated in three human
      cancers: lymphoma, myeloma and neuroblastoma, the latter specifically in the
      setting of foetal hydantoin syndrome. However, despite considerable long-term
      pharmaco-epidemiological data being available for both antiepileptic drugs,
      evidence for human carcinogenicity is not consistent and both are considered only
      possibly carcinogenic to humans. Valproate, however, has been found to exert an
      antiproliferative effect on certain cancer cell lines both in vitro and in vivo.
      A corresponding cancer-suppressive effect has not been studied in human
      epidemiological studies, though there are now preliminary reports of the use of
      valproate in human haematological and solid tumours. The anticancer activity of
      valproate appears to be driven by histone deacetylase inhibition and to be
      independent of hormone or multidrug protein resistance dependent mechanisms. The
      newer antiepileptic drugs appear to be safe, as no carcinogenicity has been
      demonstrated either during regulatory testing or in post-marketing surveillance.
      Nevertheless, the subject of cancers and epilepsy constitutes a promising agenda
      for clinical and experimental research in the future.

PMID- 15574466
TI  - The effects of very early Alzheimer's disease on the characteristics of writing
      by a renowned author.
AB  - Iris Murdoch (I.M.) was among the most celebrated British writers of the post-war
      era. Her final novel, however, received a less than enthusiastic critical
      response on its publication in 1995. Not long afterwards, I.M. began to show
      signs of insidious cognitive decline, and received a diagnosis of Alzheimer's
      disease, which was confirmed histologically after her death in 1999. Anecdotal
      evidence, as well as the natural history of the condition, would suggest that the
      changes of Alzheimer's disease were already established in I.M. while she was
      writing her final work. The end product was unlikely, however, to have been
      influenced by the compensatory use of dictionaries or thesauri, let alone by
      later editorial interference. These facts present a unique opportunity to examine
      the effects of the early stages of Alzheimer's disease on spontaneous written
      output from an individual with exceptional expertise in this area. Techniques of
      automated textual analysis were used to obtain detailed comparisons among three
      of her novels: her first published work, a work written during the prime of her
      creative life and the final novel. Whilst there were few disparities at the
      levels of overall structure and syntax, measures of lexical diversity and the
      lexical characteristics of these three texts varied markedly and in a consistent
      fashion. This unique set of findings is discussed in the context of the debate as
      to whether syntax and semantics decline separately or in parallel in patients
      with Alzheimer's disease.

PMID- 15574467
TI  - More than words: a common neural basis for reading and naming deficits in
      developmental dyslexia?
AB  - Dyslexic individuals show subtle impairments in naming pictures of objects in
      addition to their difficulties with reading. The present study investigated
      whether word reading and picture naming deficits in developmental dyslexia can be
      reduced to a common neurological impairment. Eight dyslexic subjects, impaired on
      measures of reading, spelling and naming speed, were matched for age and general
      ability with 10 control subjects. Participants were scanned using PET during two
      experimental conditions: reading words and naming pictures in the form of
      corresponding line drawings. In addition, two high-level baseline conditions were
      used to control for visual and articulatory processes. Relative to the control
      group, the dyslexic participants showed reduced activation in a left
      occipitotemporal area during both word reading and picture naming. This was the
      case even in the context of intact behavioural performance during scanning.
      Abnormal activation in this region, as reported previously for reading, is
      therefore not specific to orthographic decoding but may reflect a more general
      impairment in integrating phonology and visual information. Our investigation
      points to a common neurological basis for deficits in word reading and picture
      naming in developmental dyslexia.

PMID- 15574468
TI  - Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial
      nucleus: a role in migraine?
AB  - Migraine is a common, debilitating condition affecting up to 15% of the
      population. The ventroposteromedial nucleus of the thalamus relays trigeminal
      sensory input to the primary somatosensory cortex. In vivo electrophysiological
      recordings were made from the cell bodies of thalamocortical relay neurons in
      rats. We investigated whether microiontophoretic ejection of beta antagonists
      could inhibit thalamocortical activity in response to superior sagittal sinus
      (SSS) stimulation. We also studied 'postsynaptic' actions of these drugs through
      their modulatory actions on L-glutamate-evoked third order neuronal firing.
      Propranolol inhibited responses to SSS stimulation (P < 0.001) and L-glutamate
      ejection (P < 0.001). This was due to an action on beta receptors as it could be
      partially reversed by co-ejection of isoproterenol (SSS, P = 0.02; L-glutamate, P
      = 0.006). Serotonin (5-HT) receptor antagonism did not contribute to
      propranolol's action since the 5-HT1A receptor antagonist, (S)-WAY 100135 (P =
      0.2), and the 5-HT1B/1D receptor antagonist, GR127935 (P = 0.6), did not affect L
      glutamate-evoked neuronal firing. Atenolol inhibited both responses (SSS, P =
      0.003; L-glutamate, P < 0.001). The beta2 antagonist ICI 118,551 had no effect
      (SSS, P = 0.9; L-glutamate, P = 0.4), nor did the beta2 agonist procaterol (SSS,
      P = 0.6; L-glutamate, P = 0.9). SR 59230A (beta3 antagonist) also produced no
      significant inhibition (SSS, P = 0.7; L-glutamate, P = 0.2), indicating an
      inhibitory role for beta1 antagonists only. beta Blockers therefore may exert
      some of their therapeutic effects in migraine through beta1 adrenoceptor
      antagonist actions in the thalamus. Thalamic involvement in migraine is
      attractive given the complex and widespread nature of the sensory disturbance.

PMID- 15574469
TI  - Integron-mediated ESBL resistance in rare serotypes of Escherichia coli causing
      infections in an elderly population of Israel.
AB  - OBJECTIVES: To identify and characterize the aetiology of an outbreak of extra
      intestinal multidrug-resistant Escherichia coli infections in elderly patients in
      Israel. METHODS: Extended-spectrum beta-lactamase (ESBL)-producing clinical
      isolates of E. coli from extra-intestinal sources were tested for susceptibility
      to non-beta-lactam drugs, and their serotypes were determined. Restriction enzyme
      digestion, followed by PFGE of DNA purified from isolates, was used to classify
      the phylogenetic relationship between them. Plasmid DNA from five isolates of
      different serotypes was used to transform an E. coli laboratory strain. The
      plasmids were partially sequenced. RESULTS: E. coli isolates from 86 patients,
      mostly elderly, were shown to be positive for inhibitor-susceptible ESBLs, and
      more resistant to cefotaxime than to ceftazidime. Ninety-six per cent of ESBL
      producers were also resistant to gentamicin, and 100% to
      trimethoprim/sulfamethoxazole and ciprofloxacin. All isolates belonged to one of
      five serotypes. PFGE analysis of purified DNA yielded 17 profiles. Sequencing of
      plasmids isolated from the transformants identified sul1, aac(6')-Ib and bla(CTX
      M-2). These genes were embedded in an integron, InS21. CONCLUSIONS: Extra
      intestinal infections with ESBL-producing E. coli of different serotypes and
      probably mixed clonality showed a surprising homogeneity in resistance profiles,
      with 100% being co-resistant to ciprofloxacin and trimethoprim/sulfamethoxazole,
      and 96% to gentamicin. Plasmid DNA from three isolates from different serotypes
      contained integron InS21, previously demonstrated in Salmonella enterica from
      Argentina. This is the first molecular identification of an ESBL gene and
      integron in Israel or neighbouring geographical areas.

PMID- 15574470
TI  - Italian metallo-beta-lactamases: a national problem? Report from the SENTRY
      Antimicrobial Surveillance Programme.
AB  - OBJECTIVES: As part of the SENTRY Antimicrobial Surveillance Programme, 383 non
      replicative randomly collected Pseudomonas aeruginosa isolates were collected
      during 1999-2002. These strains originated from three geographically distinct
      hospitals within Italy: Genoa (Northern Italy); Rome and Catania (Sicily), and
      were further studied to identify the prevalence of metallo-beta-lactamase
      (MbetaL) alleles across Italy and to determine their genetic details. METHODS:
      Multidrug-resistant (MDR) strains were identified by MIC analysis followed by
      genotyping and PCR-based strategies. RESULTS: Initial MIC analysis identified 31
      MDR isolates that displayed an Etest MbetaL-positive phenotype. Of these, 25
      produced either the MbetaL VIM-1 or IMP-13 as detected by PCR and sequencing. VIM
      1-producing isolates were found at all sites, whereas IMP-13-producing isolates
      were only found in Rome. MbetaL-producing isolates were found at all Italian
      SENTRY sites and together amounted to 6.5% of all P. aeruginosa isolates. Genetic
      analysis indicated that many strains contained multiple integrons and identified
      two novel MbetaL integrons, one from the site in Genoa and one from Sicily.
      Integrons identical in structure and sequence to In70, the first identified and
      characterized bla(VIM)-containing integron from Verona, were found in isolates
      with distinct ribotypes at the Roman and Sicilian sites indicating that this
      integron has recently disseminated across Italy. All 25 MbetaL-producing isolates
      were genetically linked in that all isolates contained Tn5051 sequences and all
      harboured the insertion sequence IsPa7 which may be involved in the mobilization
      of these resistance alleles. CONCLUSIONS: Taken together, these results indicate
      that Italy has a nationwide problem of MDR P. aeruginosa produced by mobile
      MbetaL genes.

PMID- 15574471
TI  - The OPTAMA programme: utilizing MYSTIC (2002) to predict critical pharmacodynamic
      target attainment against nosocomial pathogens in Europe.
AB  - OBJECTIVES: The Optimising Pharmacodynamic Target Attainment using the MYSTIC
      (Meropenem Yearly Susceptibility Test Information Collection) Antibiogram
      (OPTAMA) programme identifies antibiotic regimens with the highest probability of
      attaining critical pharmacodynamic targets, accounting for the inherent
      variability in pharmacokinetics, dosages and MIC distributions. METHODS: European
      MIC data were obtained from the MYSTIC programme. Pharmacodynamic target
      attainment was calculated by Monte Carlo simulation for meropenem, imipenem,
      ceftazidime, cefepime, piperacillin/tazobactam and ciprofloxacin against
      Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas
      aeruginosa. RESULTS: Significant differences in probability of target attainment
      were found, with Northern Europe demonstrating the highest probabilities of
      target attainment and Eastern Europe the lowest. The carbapenems had the highest
      target attainments and susceptibility levels across all regions and pathogens.
      The cephalosporins demonstrated high target attainments and susceptibility
      results against E. coli and K. pneumoniae in Northern and Southern Europe.
      Piperacillin/tazobactam and ciprofloxacin had the lowest levels for both
      parameters in all regions. Desirable target attainment was not achieved (except
      for carbapenems in Northern Europe) for A. baumannii and P. aeruginosa; thus,
      combination therapy may be appropriate empirical therapy for these pathogens in
      Southern and Eastern Europe. The closest correlations between target attainment
      and susceptibility were for meropenem 1 g every 8 h, imipenem 0.5 g every 6 h and
      ceftazidime 1 g every 8 h. CONCLUSIONS: The study highlighted significant
      overestimations between the probability of target attainment and the reported
      percentage susceptibility, particularly for piperacillin/tazobactam and
      ciprofloxacin. The approach of the OPTAMA programme provides a novel tool which
      complements susceptibility data to help in the selection of appropriate empirical
      antibiotic therapy.

PMID- 15574472
TI  - Fluoroquinolone consumption and resistance in haematology-oncology patients:
      ecological analysis in two university hospitals 1999-2002.
AB  - OBJECTIVES: To compare rates of in vitro fluoroquinolone resistance of bacterial
      isolates obtained from inpatients of two haematology-oncology services with high
      and low fluoroquinolone consumption. METHODS: Two hospitals with consistently
      high (A) and low (B) fluoroquinolone use in their haematology-oncology services
      between the years 1999 and 2002 were identified in a hospital antibiotic use
      surveillance project. Rates of in vitro resistance to fluoroquinolones in
      inpatients of the services were determined for Escherichia coli and coagulase
      negative staphylococcal bloodstream isolates, and also for Pseudomonas aeruginosa
      and Staphylococcus aureus isolates from any site. RESULTS: Fluoroquinolone
      resistance of E. coli was significantly higher in hospital A than in hospital B,
      but there was no such correlation between fluoroquinolone use and resistance
      rates for P. aeruginosa and staphylococci. CONCLUSION: The impact of antibiotic
      consumption on the prevalence of resistance may differ widely between different
      pathogens. Interventions using ecological analyses of the relationship between
      hospital antibiotic use and resistance need to consider pathogen-specific
      dynamics in the emergence and control of bacterial resistance.

PMID- 15574473
TI  - Epidemiology of antimicrobial resistance in enterococci of animal origin.
AB  - OBJECTIVE: We evaluated the epidemiology of antimicrobial resistance in
      enterococci from animal farms and the potential relation of resistance to
      antimicrobial use. METHODS: Enterococci from faecal samples from 18 beef cattle,
      18 dairy cattle, 18 swine, 13 chicken, and eight turkey farms were prospectively
      evaluated over a 6 year period from 1998 to 2003. RESULTS: We evaluated 1256
      isolates of Enterococcus faecium and 656 isolates of Enterococcus faecalis. None
      was vancomycin resistant. Quinupristin/dalfopristin, gentamicin and ciprofloxacin
      resistance rates in E. faecium were 2%, 0% and 55% in beef cattle, 8%, 7% and 47%
      in dairy cattle, 21%, 1% and 47% in swine, 85%, 12% and 23% in chicken, and 52%,
      13% and 24% in turkey isolates, respectively. For E. faecalis, gentamicin
      resistance rates were 0% in beef cattle, 24% in dairy cattle, 37% in swine, 32%
      in chicken, and 29% in turkey isolates, whereas 12%, 9%, 21%, 64% and none of
      isolates from beef, dairy, swine, chicken, and turkey farms, respectively, were
      resistant to ciprofloxacin. Quinupristin/dalfopristin resistance in E. faecium
      was more common on chicken and turkey farms using virginiamycin (P<0.0001 for
      both) compared with farms not using a streptogramin, gentamicin resistance was
      more common on dairy farms using gentamicin (P<0.0001) compared with farms not
      using this antibiotic, and ciprofloxacin resistance was more common on turkey and
      dairy farms using enrofloxacin compared with those with no enrofloxacin use
      (P=0.02 and P=0.04, respectively). For E. faecalis, gentamicin resistance was
      more frequently detected on dairy and swine farms using gentamicin (P<0.0001 and
      P=0.0052, respectively) and ciprofloxacin resistance was more common on beef
      farms using enrofloxacin (P<0.0001) compared with farms not using these
      antimicrobials. PFGE showed multiple strain types with some clones common between
      animals of the same animal species. CONCLUSIONS: This study shows the presence of
      a significant reservoir of antibiotic-resistant enterococci among farm animals.
      Resistance was more common on farms using antimicrobial agents.

PMID- 15574474
TI  - Antibiotic cycling: more than it might seem?
AB  - In the present battle against the rising tide of resistance, several
      interventions have been proposed to help control the situation. One of these is a
      process of planned antibiotic restriction, introduced through cycling drug
      selection based on local surveillance. Although such antibiotic cycling has been
      the subject of much discussion for 20 years, there are relatively few data
      available to assess its worth. A recent systematic review found only four studies
      worthy of inclusion and concluded that antibiotic cycling could not, at present,
      be promoted as a methodology to control resistance. This paper considers the
      complete literature and through demonstrating consistent benefits across the
      breadth and depth of the findings, suggests that whereas further work is
      required, nevertheless antibiotic cycling-as part of a suite of control measures
      is a valid option.

PMID- 15574475
TI  - Reduction of the fitness burden of quinolone resistance in Pseudomonas
      aeruginosa.
AB  - OBJECTIVES: Quinolone resistance in the opportunistic pathogen Pseudomonas
      aeruginosa is commonly caused by mutations that alter the target molecules DNA
      gyrase/topoisomerase IV, or cause activation of various efflux systems. We have
      analysed the effect of quinolone resistance caused by DNA gyrase/topoisomerase IV
      mutations on bacterial fitness. METHODS: Norfloxacin-resistant mutants were
      isolated and by DNA sequencing the mutations conferring resistance were
      identified. Mutant fitness was determined by measuring growth rates in vitro.
      Mutants with reduced growth rates were serially passaged to obtain growth
      compensated mutants. The level of DNA supercoiling was determined by isolating
      plasmid DNA from the susceptible, resistant and compensated mutants and comparing
      the topoisomer distribution patterns by gel electrophoresis in the presence of
      chloroquine. RESULTS: Low-level resistance (4-48 mg/L) was caused by single
      mutations in gyrA or gyrB. Among these strains, three out of eight mutants showed
      lower fitness, whereas high-level resistant (>256 mg/L) mutants with double
      mutations in gyrA and parC, parE, nfxB or unknown genes all showed a reduced
      fitness. Slow-growing resistant mutants with a gyrA mutation had decreased DNA
      supercoiling. After serial passage in laboratory medium, mutant fitness was
      increased by compensatory mutation(s) that restored supercoiling to normal
      levels. The compensatory mutation(s) was not located in any of the genes (gyrAB,
      topA, parCE, hupB, fis, hupN, himAD or PA5348) that were expected to affect
      supercoiling. CONCLUSIONS: Our results show that 'no cost' and compensatory
      mutations are common in quinolone-resistant P. aeruginosa.

PMID- 15574476
TI  - In vitro activity of bergamot natural essence and furocoumarin-free and distilled
      extracts, and their associations with boric acid, against clinical yeast
      isolates.
AB  - OBJECTIVES: There is very little information, to date, on the antifungal activity
      of bergamot oil. In this study, we investigated the in vitro activity of three
      bergamot oils (natural essence, furocoumarin-free extract and distilled extract)
      against clinically relevant Candida species. We studied the two derivatives,
      components of Italian pharmaceutical products, that are supposed to be less toxic
      than the essential oil. METHODS: In vitro susceptibility of 40 clinical isolates
      of Candida spp. (Candida albicans, n=20; Candida glabrata, n=13; Candida krusei,
      n=4; Candida tropicalis, n=2; Candida parapsilosis, n=1), associated with
      symptomatic and asymptomatic vulvovaginal candidiasis, was determined using a
      modification of the NCCLS M27-A2 broth microdilution method. MICs were evaluated
      for each of the oils alone and combined with sub-inhibitory concentrations of the
      well-known antiseptic, boric acid. To boric acid, all isolates had MIC values
      ranging from 0.094% to 0.187% (w/v). RESULTS: At 24 h readings, the MIC(90 )s
      (for all isolates) were (v/v): 5% for natural essence of bergamot, 2.5% for the
      furocoumarin-free extract, and 1.25% for the distilled extract. At the 48 h
      reading, these values increased to >10%, 5% and 2.5%, respectively. At both
      readings, MIC(90 )s for all oil+boric acid combinations were significantly lower
      than corresponding values for the oils alone (P <0.05). CONCLUSIONS: These data
      indicate that bergamot oils are active in vitro against Candida spp., suggesting
      their potential role for the topical treatment of Candida infections.

PMID- 15574477
TI  - Rapid detection of extended-spectrum beta-lactamase (ESBL)-producing organisms in
      blood culture.

PMID- 15574478
TI  - A rapid method of impregnating endotracheal tubes and urinary catheters with
      gendine: a novel antiseptic agent.
AB  - OBJECTIVES: To test the efficacy of gendine, a novel antiseptic, containing
      Gentian Violet and chlorhexidine, in coating different medical devices, including
      endotracheal tubes (ETT) and urinary catheters (UC). METHODS: We determined the
      antimicrobial efficacy and cytotoxicity of ETT and UC segments coated, through an
      instant dip method, with gendine. Using the modified Kirby-Bauer method, gendine
      coated devices showed zones of inhibition of >/=15 mm against methicillin
      resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli
      and Candida parapsilosis. RESULTS: Gendine-coated endotracheal tubes (GND-ETT)
      soaked in bronchoalveolar fluid (BAL) and incubated at 37 degrees C maintained a
      zone of inhibition of >/=15 mm against MRSA and P. aeruginosa for at least 3
      weeks. Similarly, gendine-coated urinary catheters (GND-UC), soaked in urine,
      maintained a zone of inhibition of >/=15 mm against E. coli for 8 weeks. Using
      the minimum essential media elution method in mouse fibroblast cells, GND-ETT and
      GND-UC were found to be non-cytotoxic. Gendine-coated UC significantly reduced
      the amount of viable MRSA, E. coli or C. parapsilosis organisms adhering to their
      surfaces when compared with silver/hydrogel-coated urinary catheters or control
      uncoated catheters (P < 0.01). Similarly GND-ETT significantly reduced the
      adherence of the same organisms as well as P. aeruginosa when compared with
      control (P </= 0.02). CONCLUSIONS: GND-ETT and GND-UC impregnated using an
      instantaneous dip method, were shown to have broad-spectrum activity, prolonged
      antimicrobial durability and high efficacy in inhibiting adherence of organisms
      commonly causing nosocomial pneumonia and urinary tract infection. Furthermore,
      these coated devices were shown to be non-cytotoxic.

PMID- 15574479
TI  - Antimicrobial susceptibility of bifidobacteria.
AB  - OBJECTIVES: The aim of our study was to analyse the antibiotic susceptibility of
      various strains of Bifidobacterium spp. to a wide range of antimicrobial agents.
      METHODS: Fifty strains belonging to eight species of bifidobacteria, isolated
      from humans, animals or probiotic products, were tested for susceptibility to 30
      antibiotics by disc diffusion on Brucella agar supplemented with 5% laked sheep
      blood and vitamin K1 (1 mg/L). MICs of nine anti-anaerobe agents, including three
      new molecules (telithromycin, linezolid and gatifloxacin), were determined using
      the reference agar-dilution method. RESULTS: All strains of bifidobacteria,
      whatever the species, were sensitive to penicillins: penicillin G, amoxicillin
      (MIC(50) 0.06 mg/L), piperacillin, ticarcillin, imipenem and usually anti-Gram
      positive antibiotics (macrolides, clindamycin, pristinamycin, vancomycin and
      teicoplanin). Susceptibility to cefalothin and cefotetan was variable. Most
      isolates (70%) were resistant to fusidic acid. As expected, high resistance rates
      were observed for aminoglycosides. Metronidazole, an agent known for its anti
      anaerobe activity, was ineffective against 38% of the strains. The newly
      commercialized molecules, telithromycin, linezolid and gatifloxacin, were active
      with MIC(50)S of 1 mg/L. The only variation in susceptibility observed among the
      different species concerned Bifidobacterium breve, which appeared to be generally
      more resistant. Potentially acquired resistance was only observed against
      tetracycline and minocycline, in 14% of the strains. CONCLUSIONS: With regard to
      a general concern about the safety of probiotics, such as potential
      transferability of resistance determinants, bifidobacteria, with their low
      natural and acquired resistance to 30 antibiotics, appear risk-free.

PMID- 15574480
TI  - Distribution of streptogramin resistance determinants among Enterococcus faecium
      from a poultry production environment of the USA.
AB  - OBJECTIVES: The impact of agricultural use of antimicrobials on the present and
      future efficacy of therapeutic drugs in human medicine is a growing public
      concern. Quinupristin/dalfopristin has been approved to treat human disease
      caused by vancomycin-resistant Enterococcus faecium and is related to
      virginiamycin, a streptogramin complex that has long been used in USA agriculture
      poultry production. METHODS: Streptogramin-resistant isolates of E. faecium from
      poultry production environments on the eastern seaboard were recovered without
      selection for streptogramin resistance and examined using ribotyping to evaluate
      clonal bias. Colony PCR screening for the previously described streptogramin
      resistance determinants erm(A), erm(B), msr(C), vgb(A), vat(D) and vat(E) was
      performed to determine the prevalence of streptogramin resistance mechanisms from
      these environments. RESULTS: The collection of E. faecium isolates was unevenly
      distributed among 28 ribogroups and did not cluster geographically. The most
      prevalent ribogroups was composed of isolates that possessed diverse
      antimicrobial resistance profiles. Of the 127 isolates examined, 63% were
      resistant to quinupristin/dalfopristin. The resistance determinants erm(A) and
      erm(B) were observed among 6% and 10%, respectively, of streptogramin-resistant
      isolates. msr(C) was detected in a single isolate that was resistant to macrolide
      and lincosamide antimicrobials. The streptogramin B hydrolase vgb(A) and the
      streptogramin A acetyltransferases genes vat(D) and vat(E) were not detected in
      any of the E. faecium isolates. CONCLUSIONS: These results indicate that there is
      widespread resistance to streptogramin antimicrobials among E. faecium throughout
      the poultry production region in this study and that the mechanisms of resistance
      to streptogramin antimicrobials within this population remain largely
      uncharacterized.

PMID- 15574481
TI  - Treatment of long-term intravascular catheter-related bacteraemia with antibiotic
      lock: randomized, placebo-controlled trial.
AB  - OBJECTIVES: The use of an antibiotic lock (AB-lock) for the treatment of catheter
      related bloodstream infection (CRBSI) has been suggested, but randomized trials
      have never been performed. METHODS: A randomized, blinded, multicentre trial was
      set up to compare an AB-lock-containing vancomycin for Gram-positive or
      ceftazidime for Gram-negative bacteria-with placebo, in addition to parenteral AB
      therapy. We included only CRBSI from a long-term intravascular device (LTID)
      whether tunnelled or totally implanted. RESULTS: During 30 months, 174 patients
      with an LTID and bacteraemia were evaluated, of whom 85 had a CRBSI. Forty-six
      patients were included. Frequent reasons for exclusion were: catheter not vacant
      for >8-12 h/day for the AB-lock (n =10); yeast infection or mixed Gram
      positive/negative infections (n =13); catheter removal preferred by the treating
      physician (n =7); and CRBSI <14 days after insertion or pocket/tunnel infection
      (n =10). Forty-four patients met the criteria for modified intention-to-treat
      analysis. The primary endpoint was failure to cure the CRBSI or relapse with the
      same strain. On study day 180 by Kaplan-Meier analysis, this occurred in 33%
      (seven of 21) in the AB-lock arm and in 57% (13 of 23) in the placebo arm (hazard
      ratio 0.55, P =0.10). A relapse with the same strain occurred in 9/23 with the
      placebo and 3/21 with the AB-lock (P =0.06). CONCLUSION: Future studies should
      take into account the barriers to the use of AB-lock observed in this study. Most
      importantly, shorter lock dwell times and broader spectrum locks (e.g.
      antiseptic) should be investigated to target a larger patient population.

PMID- 15574482
TI  - Comparison of QTL controlling seedling vigour under different temperature
      conditions using recombinant inbred lines in rice (Oryza sativa).
AB  - BACKGROUND AND AIMS: Seedling vigour is one of the major determinants for stable
      stand establishment in rice (Oryza sativa), especially in a direct seeding
      cropping system. The objectives of this study were to identify superior alleles
      with consistent effects on seedling vigour across different temperature
      conditions and to investigate genotype x environmental temperature interactions
      for seedling vigour QTL. METHODS: A set of 282 F13 recombinant inbred lines
      (RILs) derived from a rice cross were assessed for four seedling vigour traits at
      three temperatures (25 degrees C, 20 degrees C and 15 degrees C). Using a linkage
      map with 198 marker loci, the main-effect QTL for the traits were mapped by
      composite interval mapping. KEY RESULTS: A total of 34 QTL for the four seedling
      vigour traits were identified. Of these QTL, the majority (82%) were clustered
      within five genomic regions, designated as QTL qSV-3-1, qSV-3-2, qSV-5, qSV-8-1
      and qSV-8-2. All of these five QTL had small individual effects on the traits,
      explaining 3.1-15.8 % of the phenotypic variation with a mean of 7.3 %. QTL qSV-3
      1, qSV-3-2 and qSV-8-1 showed almost consistent effects on the traits across all
      three temperatures while qSV-5 and qSV-8-2 had effects mainly at the 'normal'
      temperatures of 20 degrees C and 25 degrees C. Among the five QTL identified, all
      and four showed additive effects on shoot length and germination rate,
      respectively. The contributions of these five QTL to shoot length and germination
      rate were also much larger than those to the other two traits. CONCLUSIONS: A few
      of genomic regions (or QTL) were identified as showing effects on seedling
      vigour. For these QTL, significant genotype x environmental temperature
      interactions were found and these interactions appeared to be QTL-specific. Among
      the four seedling vigour traits measured, shoot length and germination rate could
      be used as relatively good indicators to evaluate the level of seedling vigour in
      rice.

PMID- 15574483
TI  - Mechanical adaptations of cleavers (Galium aparine).
AB  - BACKGROUND AND AIMS: Cleavers (Galium aparine) is a fast-growing herbaceous
      annual with a semi-self-supporting, scrambling-ascending growth habit. Mature
      plants often use upright species for support. It is common in hedgerows and on
      waste ground. This study aims to characterize the mechanical behaviour of the
      stem and roots of cleavers and relate this to the arrangement of structural
      tissue, the net microfibrillar orientations in the cell walls, and plant growth
      habit. METHODS: The morphology and mechanics of mature cleavers was investigated
      using plants grown in pots and ones collected from the grounds at the University
      of Lincoln, Lincoln, UK. Tensile tests were carried out on the stem and the basal
      section of the first-order lateral roots. The net orientation of cellulose
      microfibrils in the cell walls was investigated using polarized light microscopy.
      KEY RESULTS: Results show that the basal regions of the stem and first-order
      lateral roots were highly extensible. Breaking strains of 24 +/- 7% were recorded
      for the stem base and 28 +/- 6% for the roots. Anatomical observations showed
      that the lower stem (base + 100 mm) was circular in cross-section with a solid
      central core of vascular tissue, whereas further up the stem the transverse
      section showed a typical four-angled shape with a ring-like arrangement of
      vascular tissue and sclerenchyma bundles in the corners. The net orientation of
      wall microfibrils in the secondary xylem diverges from the longitudinal by
      between 8 and 9 degrees . CONCLUSIONS: The basal region of the stem of cleavers
      is highly extensible, but the mechanism by which the stem is able to withstand
      such high breaking strains is unclear; reorientation of the cellulose fibrils in
      the stem along the axis of loading is not thought to be responsible.

PMID- 15574484
TI  - Construction of stabilized proteins by combinatorial consensus mutagenesis.
AB  - We constructed stabilized variants of beta-lactamase (BLA) from Enterobacter
      cloacae by combinatorial recruitment of consensus mutations. By aligning the
      sequences of 38 BLA homologs, we identified 29 positions where the E.cloacae gene
      differs from the consensus sequence of lactamases and constructed combinatorial
      libraries using mixtures of mutagenic oligonucleotides encompassing all 29
      positions. Screening of 90 random isolates from these libraries identified 15
      variants with significantly increased thermostability. The stability of these
      isolates suggest that all tested mutations make additive contributions to protein
      stability. A statistical analysis of sequence and stability data identified 11
      mutations that made stabilizing contributions and eight mutations that
      destabilized the protein. A second-generation library recombining these 11
      stabilizing mutations led to the identification of BLA variants that showed
      further stabilization. The most stable variant had a mid-point of thermal
      denaturation (Tm) that was 9.1 degrees C higher than the starting molecule and
      contained eight consensus mutations. Incubation of three stabilized BLA variants
      with several proteases showed that all tested isolates have significantly
      increased resistance to proteolysis. Our data demonstrate that combinatorial
      consensus mutagenesis (CCM) allows the rapid generation of protein variants with
      improved thermal and proteolytic stability.

PMID- 15574485
TI  - Prospective cohort study of cannabis use, predisposition for psychosis, and
      psychotic symptoms in young people.
AB  - OBJECTIVE: To investigate the relation between cannabis use and psychotic
      symptoms in individuals with above average predisposition for psychosis who first
      used cannabis during adolescence. DESIGN: Analysis of prospective data from a
      population based sample. Assessment of substance use, predisposition for
      psychosis, and psychotic symptoms was based on standardised personal interviews
      at baseline and at follow up four years later. PARTICIPANTS: 2437 young people
      (aged 14 to 24 years) with and without predisposition for psychosis. MAIN OUTCOME
      MEASURE: Psychotic symptoms at follow up as a function of cannabis use and
      predisposition for psychosis at baseline. RESULTS: After adjustment for age, sex,
      socioeconomic status, urbanicity, childhood trauma, predisposition for psychosis
      at baseline, and use of other drugs, tobacco, and alcohol, cannabis use at
      baseline increased the cumulative incidence of psychotic symptoms at follow up
      four years later (adjusted odds ratio 1.67, 95% confidence interval 1.13 to
      2.46). The effect of cannabis use was much stronger in those with any
      predisposition for psychosis at baseline (23.8% adjusted difference in risk, 95%
      confidence interval 7.9 to 39.7, P = 0.003) than in those without (5.6%, 0.4 to
      10.8, P = 0.033). The risk difference in the "predisposition" group was
      significantly greater than the risk difference in the "no predisposition" group
      (test for interaction 18.2%, 1.6 to 34.8, P = 0.032). There was a dose-response
      relation with increasing frequency of cannabis use. Predisposition for psychosis
      at baseline did not significantly predict cannabis use four years later (adjusted
      odds ratio 1.42, 95% confidence interval 0.88 to 2.31). CONCLUSION: Cannabis use
      moderately increases the risk of psychotic symptoms in young people but has a
      much stronger effect in those with evidence of predisposition for psychosis.

PMID- 15574486
TI  - Renal and intestinal transport defects in Slc26a6-null mice.
AB  - SLC26A6 (PAT1, CFEX) is an anion exchanger that is expressed on the apical
      membrane of the kidney proximal tubule and the small intestine. Modes of
      transport mediated by SLC26A6 include Cl-/formate exchange, Cl-/HCO3- exchange,
      and Cl-/oxalate exchange. To study its role in kidney and intestinal physiology,
      gene targeting was used to prepare mice lacking Slc26a6. Homozygous mutant
      Slc26a6-/- mice appeared healthy and exhibited a normal blood pressure, kidney
      function, and plasma electrolyte profile. In proximal tubules microperfused with
      a low-HCO3-/high-Cl- solution, the baseline rate of fluid absorption (Jv), an
      index of NaCl transport under these conditions, was the same in wild-type and
      null mice. However, the stimulation of Jv by oxalate observed in wild-type mice
      was completely abolished in Slc26a6-null mice (P<0.05). Formate stimulation of Jv
      was partially reduced in null mice, but the difference from the response in wild
      type mice did not reach statistical significance. Apical membrane Cl-/base
      exchange activity, assayed with the pH-sensitive dye BCPCF in microperfused
      proximal tubules, was decreased by 58% in Slc26a6-/- animals (P<0.001 vs. wild
      types). In the duodenum, the baseline rate of HCO3- secretion measured in mucosal
      tissue mounted in Ussing chambers was decreased by approximately 30% (P<0.03),
      whereas the forskolin-stimulated component of HCO3- secretion was the same in
      wild-type and Slc26a6-/- mice. We conclude that Slc26a6 mediates oxalate
      stimulated NaCl absorption, contributes to apical membrane Cl-/base exchange in
      the kidney proximal tubule, and also plays an important role in HCO3- secretion
      in the duodenum.

PMID- 15574487
TI  - Inhibition of cross-bridge formation has no effect on contraction-associated
      phosphorylation of p38 MAPK in mouse skeletal muscle.
AB  - Mitogen-activated protein kinases (MAPKs), in particular p38 MAPK, are
      phosphorylated in response to contractile activity, yet the mechanism for this is
      not understood. We tested the hypothesis that the force of contraction is
      responsible for p38 MAPK phosphorylation in skeletal muscle. Extensor digitorum
      longus (EDL) muscles isolated from adult male Swiss Webster mice were stimulated
      at fixed length at 10 Hz for 15 min and then subjected to Western blot analysis
      for the phosphorylation of p38 MAPK and ERK1/2. Contralateral muscles were fixed
      at resting length and were not stimulated. Stimulated muscles showed a 2.5-fold
      increase in phosphorylated p38 MAPK relative to nonstimulated contralateral
      controls, and there was no change in the phosphorylation of ERK1/2. When
      contractile activity was inhibited with N-benzyl-p-toluene sulfonamide (BTS), a
      specific inhibitor of actomyosin ATPase, force production decreased in both a
      time- and concentration-dependent manner. Preincubation with 25, 75, and 150
      microM BTS caused 78+/-4%, 97+/-0.2%, and 99+/-0.2% inhibition in contractile
      force, respectively, and was stable after 30 min of treatment. Fluorescence
      measurements demonstrated that Ca2+ cycling was minimally affected by BTS
      treatment. Surprisingly, BTS did not suppress the level of p38 MAPK
      phosphorylation in stimulated muscles. These data do not support the view that
      force generation per se activates p38 MAPK and suggest that other events
      associated with contraction must be responsible.

PMID- 15574488
TI  - Ontogenetic expression of erythropoietin and hypoxia-inducible factor-1 alpha
      genes in subterranean blind mole rats.
AB  - Blind subterranean mole rats of the Spalax ehrenbergi superspecies in Israel have
      evolved multiple adaptive strategies to face underground hypoxia. Hypoxia
      inducible factor-1alpha (HIF-1alpha) and erythropoietin (Epo) are key factors in
      the development of normal erythropoiesis and angiogenesis. Here, we demonstrate
      via real-time polymerase chain reaction (PCR) quantification that Spalax fetal
      liver and kidney express higher levels of Epo mRNA than Rattus, generating
      reinforcement of fetal erythropoiesis underground and adapting it to life
      underground in an atmosphere of abrupt and sharp fluctuations of O2 supply. In
      neonates, Rattus liver and kidney express higher Epo levels than Spalax under
      both normoxia and hypoxia, probably due to Rattus ineffective erythropoiesis
      during embryonic life and its birth in a poorly ventilated breeding nest under
      ground. Adult Rattus kidney and liver, and adult Spalax liver express similar
      levels of Epo mRNA under normoxia and hypoxia. However, adult Spalax hypoxic
      kidney, the major site of erythropoietin production in adult mammals, shows
      levels that were twice as high as that of Rattus. Spalax expresses remarkably
      higher levels of HIF-1alpha mRNA than Rattus at all developmental stages studied,
      which peaked in neonates, as an adaptation against hypoxia.

PMID- 15574489
TI  - Self-organization of rat cardiac cells into contractile 3-D cardiac tissue.
AB  - The mammalian heart is not known to regenerate following injury. Therefore, there
      is great interest in developing viable tissue-based models for cardiac assist.
      Recent years have brought numerous advances in the development of scaffold-based
      models of cardiac tissue, but a self-organizing model has yet to be described.
      Here, we report the development of an in vitro cardiac tissue without scaffolding
      materials in the contractile region. Using an optimal concentration of the
      adhesion molecule laminin, a confluent layer of neonatal rat cardiomyogenic cells
      can be induced to self-organize into a cylindrical construct, resembling a
      papillary muscle, which we have termed a cardioid. Like endogenous heart tissue,
      cardioids contract spontaneously and can be electrically paced between 1 and 5 Hz
      indefinitely without fatigue. These engineered cardiac tissues also show an
      increased rate of spontaneous contraction (chronotropy), increased rate of
      relaxation (lusitropy), and increased force production (inotropy) in response to
      epinephrine. Cardioids have a developmental protein phenotype that expresses both
      alpha- and beta-tropomyosin, very low levels of SERCA2a, and very little of the
      mature isoform of cardiac troponin T.

PMID- 15574490
TI  - Ultrarapid mixing experiments shed new light on the characteristics of the
      initial conformational ensemble during the folding of ribonuclease A.
AB  - The earliest folding events in single-tryptophan mutants of RNase A were
      investigated by fluorescence measurements by using a combination of stopped-flow
      and continuous-flow mixing experiments covering the time range from 70 micros to
      10 s. An ultrarapid double-jump mixing protocol was used to study refolding from
      an unfolded ensemble containing only native proline isomers. The continuous-flow
      measurements revealed a series of kinetic events on the submillisecond time scale
      that account for the burst-phase signal observed in previous stopped-flow
      experiments. An initial increase in fluorescence within the 70-micros dead time
      of the continuous-flow experiment is consistent with a relatively nonspecific
      collapse of the polypeptide chain whereas a subsequent decrease in fluorescence
      with a time constant of approximately 80 micros is indicative of a more specific
      structural event. These rapid conformational changes are not observed if RNase A
      is allowed to equilibrate under denaturing conditions, resulting in formation of
      nonnative proline isomers. Thus, contrary to previous expectations, the
      isomerization state of proline peptide bonds can have a major impact on the
      structural events during early stages of folding.

PMID- 15574491
TI  - Protein chemical shifts arising from alpha-helices and beta-sheets depend on
      solvent exposure.
AB  - The NMR chemical shifts of certain atomic nuclei in proteins
      ((1)H(alpha),(13)C(alpha), and (13)C(beta)) depend sensitively on whether or not
      the amino acid residue is part of a secondary structure (alpha-helix, beta
      sheet), and if so, whether it is helix or sheet. The physical origin of the
      different chemical shifts of atomic nuclei in alpha-helices versus beta-sheets is
      a problem of long standing. We report that the chemical shift contributions
      arising from secondary structure (secondary structure shifts) depend strongly on
      the extent of exposure to solvent. This behavior is observed for (1)H(alpha),
      (13)C(alpha), and (13)C(beta) (sheet), but not for(13)C(beta) (helix), whose
      secondary structure shifts are small. When random coil values are subtracted from
      the chemical shifts of all(1)H(alpha) nuclei (Pro residues excluded) and the
      residual chemical shifts are summed to plot the mean values against solvent
      exposure, the results give a funnel-shaped curve that approaches a small value at
      full-solvent exposure. When chemical shifts are plotted instead against E(local),
      the electrostatic contribution to conformational energy produced by local dipole
      dipole interactions, a well characterized dependence of (1)H(alpha) chemical
      shifts on E(local) is found. The slope of this plot varies with both the type of
      amino acid and the extent of solvent exposure. These results indicate that
      secondary structure shifts are produced chiefly by the electric field of the
      protein, which is screened by water dipoles at residues in contact with solvent.

PMID- 15574492
TI  - Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with
      strict specificity for IgG.
AB  - Pathogenic bacteria have developed complex and diverse virulence mechanisms that
      weaken or disable the host immune defense system. IdeS (IgG-degrading enzyme of
      Streptococcus pyogenes) is a secreted cysteine endopeptidase from the human
      pathogen S. pyogenes with an extraordinarily high degree of substrate
      specificity, catalyzing a single proteolytic cleavage at the lower hinge of human
      IgG. This proteolytic degradation promotes inhibition of opsonophagocytosis and
      interferes with the killing of group A Streptococcus. We have determined the
      crystal structure of the catalytically inactive mutant IdeS-C94S by x-ray
      crystallography at 1.9-A resolution. Despite negligible sequence homology to
      known proteinases, the core of the structure resembles the canonical papain fold
      although with major insertions and a distinct substrate-binding site. Therefore
      IdeS belongs to a unique family within the CA clan of cysteine proteinases. Based
      on analogy with inhibitor complexes of papain-like proteinases, we propose a
      model for substrate binding by IdeS.

PMID- 15574493
TI  - Gamma protocadherins are required for synaptic development in the spinal cord.
AB  - Fifty-eight cadherin-related protocadherin (Pcdh) genes are tandemly arrayed in
      three clusters (alpha, beta, and gamma) on mouse chromosome 18. The large number
      of clustered Pcdh family members, their presence at synapses, and the known
      binding specificities of other cadherin superfamily members all suggest that
      these Pcdhs play roles in specifying synaptic connectivity. Consistent with this
      idea, mice lacking all 22 genes of the Pcdh-gamma cluster have decreased numbers
      of spinal cord synapses and are nearly immobile. Interpretation of this phenotype
      was complicated, however, by the fact that Pcdh-gamma loss also led to apoptosis
      of many spinal interneurons. Here, we used two methods to circumvent apoptosis
      and neurodegeneration in Pcdh-gamma mutant mice. First, we analyzed mutants
      lacking both Pcdh-gamma proteins and the proapoptotic protein Bax. Second, we
      generated a hypomorphic allele of Pcdh-gamma in which apoptosis was minimal. In
      both cases, spinal interneurons were preserved but the mice bore dramatically
      decreased numbers of spinal cord synapses and exhibited profound neurological
      defects. Moreover, synaptic function was compromised in neurons cultured from the
      hypomorphs. These results provide evidence for a direct role of gamma-Pcdhs in
      synaptic development and establish genetic tools for elucidating their
      contribution to synaptic specificity.

PMID- 15574494
TI  - Radial glia give rise to adult neural stem cells in the subventricular zone.
AB  - Neural stem cells with the characteristics of astrocytes persist in the
      subventricular zone (SVZ) of the juvenile and adult brain. These cells generate
      large numbers of new neurons that migrate through the rostral migratory stream to
      the olfactory bulb. The developmental origin of adult neural stem cells is not
      known. Here, we describe a lox-Cre-based technique to specifically and
      permanently label a restricted population of striatal radial glia in newborn
      mice. Within the first few days after labeling, these radial glial cells gave
      rise to neurons, oligodendrocytes, and astrocytes, including astrocytes in the
      SVZ. Remarkably, the rostral migratory stream contained labeled migratory
      neuroblasts at all ages examined, including 150-day-old mice. Labeling dividing
      cells with the S-phase marker BrdUrd showed that new neurons continue to be
      produced in the adult by precursors ultimately derived from radial glia.
      Furthermore, both radial glia in neonates and radial glia-derived cells in the
      adult lateral ventricular wall generated self-renewing, multipotent neurospheres.
      These results demonstrate that radial glial cells not only serve as progenitors
      for many neurons and glial cells soon after birth but also give rise to adult SVZ
      stem cells that continue to produce neurons throughout adult life. This study
      identifies and provides a method to genetically modify the lineage that links
      neonatal and adult neural stem cells.

PMID- 15574495
TI  - 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta
      induced suppressor of human gastrointestinal cancers.
AB  - Marked increased expression of cyclooxygenase 2 (COX-2), a prostaglandin
      synthesizing enzyme that is pharmacologically inhibited by nonsteroid anti
      inflammatory-type drugs, is a major early oncogenic event in the genesis of human
      colon neoplasia. We report that, in addition to inducing expression of COX-2,
      colon cancers further target the prostaglandin biogenesis pathway by ubiquitously
      abrogating expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a
      prostaglandin-degrading enzyme that physiologically antagonizes COX-2. We find
      that 15-PGDH transcript and protein are both highly expressed by normal colonic
      epithelia but are nearly undetectable in colon cancers. Using gene transfection
      to restore 15-PGDH expression in colon cancer cells strongly inhibits the ability
      of these cells to form tumors in immune-deficient mice and demonstrates 15-PGDH
      to have functional colon cancer tumor suppressor activity. In interrogating the
      mechanism for 15-PGDH expression loss in colon cancer, we determined that colonic
      15-PGDH expression is directly controlled and strongly induced by activation of
      the TGF-beta tumor suppressor pathway. These findings thus delineate an enzymatic
      pathway that induces colon cancer suppression, a pathway that is activated by TGF
      beta and mediated by 15-PGDH.

PMID- 15574496
TI  - Accelerated telomere shortening in response to life stress.
AB  - Numerous studies demonstrate links between chronic stress and indices of poor
      health, including risk factors for cardiovascular disease and poorer immune
      function. Nevertheless, the exact mechanisms of how stress gets "under the skin"
      remain elusive. We investigated the hypothesis that stress impacts health by
      modulating the rate of cellular aging. Here we provide evidence that
      psychological stress--both perceived stress and chronicity of stress--is
      significantly associated with higher oxidative stress, lower telomerase activity,
      and shorter telomere length, which are known determinants of cell senescence and
      longevity, in peripheral blood mononuclear cells from healthy premenopausal
      women. Women with the highest levels of perceived stress have telomeres shorter
      on average by the equivalent of at least one decade of additional aging compared
      to low stress women. These findings have implications for understanding how, at
      the cellular level, stress may promote earlier onset of age-related diseases.

PMID- 15574497
TI  - Diffusion of nucleoside triphosphates and role of the entry site to the RNA
      polymerase II active center.
AB  - Nucleoside triphosphates (NTPs) diffuse to the active center of RNA polymerase II
      through a funnel-shaped opening that narrows to a negatively charged pore.
      Computer simulation shows that the funnel and pore reduce the rate of diffusion
      by a factor of approximately 2 x 10(-7). The resulting limitation on the rate of
      RNA synthesis under conditions of low NTP concentration may be overcome by NTP
      binding to an entry site adjacent to the active center. Binding to the entry site
      greatly enhances the lifetime of an NTP in the active center region, and it
      prevents "backtracking" and the consequent occlusion of the active site.

PMID- 15574498
TI  - Biography of Jennifer A. Doudna.

PMID- 15574500
TI  - Strand invasion promoted by recombination protein beta of coliphage lambda.
AB  - Studies of phage lambda in vivo have indicated that its own recombination
      enzymes, beta protein and lambda exonuclease, are capable of catalyzing two
      dissimilar pathways of homologous recombination that are widely distributed in
      nature: single-strand annealing and strand invasion. The former is an enzymatic
      splicing of overlapping ends of broken homologous DNA molecules, whereas the
      latter is characterized by the formation of a three-stranded synaptic
      intermediate and subsequent strand exchange. Previous studies in vitro have shown
      that beta protein has annealing activity, and that lambda exonuclease, acting on
      branched substrates, can produce a perfect splice that requires only ligation for
      completion. The present study shows that beta protein can initiate strand
      invasion in vitro, as evidenced both by the formation of displacement loops (D
      loops) in superhelical DNA and by strand exchange between colinear single
      stranded and double-stranded molecules. Thus, beta protein can catalyze steps
      that are central to both strand annealing and strand invasion pathways of
      recombination. These observations add beta protein to a set of diverse proteins
      that appear to promote recognition of homology by a unitary mechanism governed by
      the intrinsic dynamic properties of base pairs in DNA.

PMID- 15574499
TI  - IkappaB kinase beta phosphorylates Dok1 serines in response to TNF, IL-1, or
      gamma radiation.
AB  - Dok1 is an abundant Ras-GTPase-activating protein-associated tyrosine kinase
      substrate that negatively regulates cell growth and promotes migration. We now
      find that IkappaB kinase beta (IKKbeta) associated with and phosphorylated Dok1
      in human epithelial cells and B lymphocytes. IKKbeta phosphorylation of Dok1
      depended on Dok1 S(439), S(443), S(446), and S(450). Recombinant IKKbeta also
      phosphorylated Dok1 or Dok1 amino acids 430-481 in vitro. TNF-alpha, IL-1, gamma
      radiation, or IKKbeta overexpression phosphorylated Dok1 S(443), S(446), and
      S(450) in vivo, as detected with Dok1 phospho-S site-specific antisera. Moreover,
      Dok1 with S(439), S(443), S(446), and S(450) mutated to A was not phosphorylated
      by IKKbeta in vivo. Surprisingly, mutant Dok1 A(439), A(443), A(446), and A(450)
      differed from wild-type Dok1 in not inhibiting platelet-derived growth factor
      induced extracellular signal-regulated kinase 1/2 phosphorylation or cell growth.
      Mutant Dok1 A(439), A(443), A(446), and A(450) also did not promote cell
      motility, whereas wild-type Dok1 promoted cell motility, and Dok1 E(439), E(443),
      E(446), and E(450) further enhanced cell motility. These data indicate that
      IKKbeta phosphorylates Dok1 S(439)S(443) and S(446)S(450) after TNF-alpha, IL-1,
      or gamma-radiation and implicate the critical Dok1 serines in Dok1 effects after
      tyrosine kinase activation.

PMID- 15574501
TI  - The bacteriophage T4 late-transcription coactivator gp33 binds the flap domain of
      Escherichia coli RNA polymerase.
AB  - Transcription of bacteriophage T4 late genes requires concomitant DNA
      replication. T4 late promoters, which consist of a single 8-bp -10 motif, are
      recognized by a holoenzyme containing Escherichia coli RNA polymerase core and
      the T4-encoded promoter specificity subunit, gp55. Initiation of transcription at
      these promoters by gp55-holoenzyme is inefficient, but is greatly activated by
      the DNA-loaded DNA polymerase sliding clamp, gp45, and the coactivator, gp33. We
      report that gp33 attaches to the flap domain of the Escherichia coli RNA
      polymerase beta-subunit and that this interaction is essential for activation.
      The beta-flap also mediates recognition of -35 promoter motifs by binding to
      sigma(70) domain 4. The results suggest that gp33 is an analogue of sigma(70)
      domain 4 and that gp55 and gp33 together constitute two parts of the T4 late
      sigma. We propose a model for the role of the gp45 sliding clamp in activation of
      T4 late-gene transcription.

PMID- 15574502
TI  - Evolution of xylem lignification and hydrogel transport regulation.
AB  - In vascular plants, the polysaccharide-based walls of water-conducting cells are
      strengthened by impregnation with the polyphenolic polymer lignin. The fine-scale
      patterning of lignin deposition in water-conducting cells is shown here to vary
      phylogenetically across vascular plants. The extent to which water transport in
      xylem cells can be modified in response to changes in the ionic content of xylem
      sap also is shown to vary in correlation with variation in lignification
      patterns, consistent with the proposed mechanism for hydraulic response through
      size change of middle-lamella pectins. This covariation suggests that the fine
      scale distribution of hydrophilic polysaccharides and hydrophobic lignin can
      affect hydraulic as well as mechanical properties, and that the evolutionary
      diversification of vascular cells thus reflects biochemical as well as
      morphological innovations evolved to fulfill opposing cell functions of transport
      and structural support.

PMID- 15574503
TI  - Multiple spatially distinct types of facultative heterochromatin on the human
      inactive X chromosome.
AB  - Heterochromatin is defined classically by condensation throughout the cell cycle,
      replication in late S phase and gene inactivity. Facultative heterochromatin is
      of particular interest, because its formation is developmentally regulated as a
      result of cellular differentiation. The most extensive example of facultative
      heterochromatin is the mammalian inactive X chromosome (Xi). A variety of histone
      variants and covalent histone modifications have been implicated in defining the
      organization of the Xi heterochromatic state, and the features of Xi
      heterochromatin have been widely interpreted as reflecting a redundant system of
      gene silencing. However, here we demonstrate that the human Xi is packaged into
      at least two nonoverlapping heterochromatin types, each characterized by specific
      Xi features: one defined by the presence of Xi-specific transcript RNA, the
      histone variant macroH2A, and histone H3 trimethylated at lysine 27 and the other
      defined by H3 trimethylated at lysine 9, heterochromatin protein 1, and histone
      H4 trimethylated at lysine 20. Furthermore, regions of the Xi packaged in
      different heterochromatin types are characterized by different patterns of
      replication in late S phase. The arrangement of facultative heterochromatin into
      spatially and temporally distinct domains has implications for both the
      establishment and maintenance of the Xi and adds a previously unsuspected degree
      of epigenetic complexity.

PMID- 15574504
TI  - Wound healing in the kidney: complex interactions in renal interstitial
      fibrogenesis.

PMID- 15574506
TI  - Renal failure associated with cancer and its treatment: an update.

PMID- 15574507
TI  - Complement factor h limits immune complex deposition and prevents inflammation
      and scarring in glomeruli of mice with chronic serum sickness.
AB  - Factor H is the major complement regulator in plasma. Abnormalities in factor H
      have been implicated in membranoproliferative glomerulonephritis in both humans
      and experimental animals. It has been shown that factor H on rodent platelets
      functions analogously to human erythrocyte complement receptor 1 in its role to
      traffic immune complexes to the mononuclear phagocyte system. C57BL/6 factor H
      deficient mice (Cfh(-/-)) and wild-type (wt) controls were immunized daily for 5
      wk with heterologous apoferritin to study the chronic serum sickness GN model.
      Immunizations were started in 6- to 8-wk-old mice, which was before the
      development of spontaneous membranoproliferative glomerulonephritis in some Cfh(
      /-) animals. Glomerular deposition of IgG immune complexes in glomeruli was
      qualitatively and quantitatively increased in Cfh(-/-) mice compared with wt
      mice. Consistent with the increase in glomerular immune complexes and possibly
      because of alternative pathway complement activation, Cfh(-/-) mice had increased
      glomerular C3 deposition. Wt mice developed no glomerular pathology. In contrast,
      Cfh(-/-) mice developed diffuse proliferative GN with focal crescents and
      glomerulosclerosis. In addition, there was significantly increased expression of
      collagen IV, fibronectin, and laminin mRNA in Cfh(-/-) glomeruli. These data show
      a role for platelet-associated factor H to process immune complexes and limit
      their accumulation in glomeruli. Once deposited in glomeruli, excessive
      complement activation can lead to glomerular inflammation and the rapid
      development of a scarring phenotype.

PMID- 15574508
TI  - Variable pump flow-based Doppler ultrasound method: a novel approach to the
      measurement of access flow in hemodialysis patients.
AB  - Decreasing vascular access flow (Qa) is an important predictor of future access
      thrombosis and malfunction for hemodialysis (HD) patients. Among all of the
      methods for determining Qa, the variable pump flow (VPF) Doppler method measures
      Qa according to the change in Doppler signal between the arterial and the venous
      needles under different pump flow. After this technique was combined with
      spectral analysis of Duplex Doppler imaging, the variable pump flow-based Doppler
      ultrasound method (VPFDUM) for Qa measurement was developed. This study compared
      the reproducibility and correlation of Qa measurements for three different
      methods-VPFDUM, ultrasound dilution method (UDM), and conventional Doppler
      ultrasound method (CDUM)-in 55 HD patients. The mean value of Qa by VPFDUM (870.8
      +/- 412.0 ml/min) was close to that by UDM (868.6 +/- 417.9 ml/min) but higher
      than that by CDUM (either of the above values versus 685.1 +/- 303.6 ml/min; P <
      0.005). The mean values of coefficient of variation were similar by VPFDUM (1.6%)
      and UDM (1.4%) but lower than that by CDUM (either of the above values versus
      6.8%; P < 0.01). The correlation coefficient and intraclass correlation
      coefficient of the repeated Qa measurements by VPFDUM (0.985 and 0.993; P <
      0.001) were also similar to those by UDM (0.992 and 0.995; P < 0.001) but
      slightly higher than those by CDUM (0.917 and 0.948; P < 0.005). Either the
      reproducibility of VPFDUM (r=0.98, P < 0.0001) or the correlation between VPFDUM
      and UDM (r=0.99, P < 0.0001) in Qa measurements is good. The unassisted patency
      of vascular access at 6 mo was significantly poorer in patients with Qa <500
      ml/min than those with Qa >500 ml/min (13.6% versus 92.2%; P < 0.0001). In
      conclusion, VPFDUM is a noninvasive, accurate, and reliable procedure for Qa
      measurement and prediction of the prognosis of vascular access in HD patients.

PMID- 15574509
TI  - Biochemical and cellular effects of direct maxacalcitol injection into
      parathyroid gland in uremic rats.
AB  - The most important etiological factors of resistance to medical treatments for
      secondary hyperparathyroidism are the decreased contents of the vitamin D
      receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells and a severely
      swollen parathyroid gland (PTG) as a result of hyperplasia. The effects of direct
      maxacalcitol (OCT) injection into PTG in terms of these factors were investigated
      in this study. The PTG of Sprague-Dawley rats that were 5/6 nephrectomized and
      fed a high-phosphate diet were treated by a direct injection of OCT (DI-OCT) or
      vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (PTH),
      Ca(2+), and phosphorus levels, in VDR and CaSR expression levels in parathyroid
      cells, and in Ca(2+)-PTH curves were examined. Apoptosis was analyzed by the
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and
      DNA electrophoresis for PTG. DI-OCT markedly decreased serum intact PTH level,
      and a significant difference in this level between DI-OCT and DI-vehicle was
      observed. However, serum Ca(2+) and phosphorus levels did not changed markedly in
      both groups. The upregulations of both VDR and CaSR, the clear shift to the left
      downward in the Ca(2+)-PTH curve, and the induction of apoptosis after DI-OCT
      were observed. These findings were not observed in the DI-vehicle-treated rats.
      Moreover, these effects of DI-OCT were confirmed by the DI-OCT into one PTG and
      DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce
      simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG,
      and these effects may provide a strategy for strongly suppressing PTH levels in
      very severe secondary hyperparathyroidism.

PMID- 15574510
TI  - Epithelial Ca2+ and Mg2+ channels in health and disease.
AB  - A near constancy of the extracellular Ca(2+) and Mg(2+) concentration is required
      for numerous physiologic functions at the organ, tissue, and cellular levels.
      This suggests that minor changes in the extracellular concentration of these
      divalents must be detected to allow the appropriate correction by the homeostatic
      systems. The maintenance of the Ca(2+) and Mg(2+) balance is controlled by the
      concerted action of intestinal absorption, renal excretion, and exchange with
      bone. After years of research, rapid progress was made recently in identification
      and characterization of the Ca(2+) and Mg(2+) transport proteins that contribute
      to the delicate balance of divalent cations. Expression-cloning approaches in
      combination with knockout mice models and genetic studies in families with a
      disturbed Mg(2+) balance revealed novel Ca(2+) and Mg(2+) gatekeeper proteins
      that belong to the super family of the transient receptor potential (TRP)
      channels. These epithelial Ca(2+) (TRPV5 and TRPV6) and Mg(2+) channels (TRPM6
      and TRPM7) form prime targets for hormonal control of the active Ca(2+) and
      Mg(2+) flux from the urine space or intestinal lumen to the blood compartment.
      This review describes the characteristics of epithelial Ca(2+) and Mg(2+)
      transport in general and highlights in particular the distinctive features and
      the physiologic relevance of these new epithelial Ca(2+) and Mg(2+) channels in
      (patho)physiologic situations.

PMID- 15574511
TI  - Bone morphogenic protein-7 inhibits monocyte-stimulated TGF-beta1 generation in
      renal proximal tubular epithelial cells.
AB  - It has been demonstrated that bone morphogenic protein-7 (BMP-7) stimulates
      formation of hyaluronan (HA)-based cables on the cell surface of renal proximal
      tubular cells and that these cables mediate monocyte binding. Furthermore,
      interaction of monocytes with proximal tubule cell (PTC) surface intracellular
      adhesion molecule (ICAM) stimulates the synthesis of TGF-beta1. This study
      examined the effect of BMP-7 on monocyte-stimulated TGF-beta1 synthesis under
      conditions of basal and stimulated ICAM expression. Monocyte (U937 cells)
      dependent stimulation of TGF-beta1 promoter activity and protein synthesis was
      reduced by addition of BMP-7 for 24 h before addition of U937 cells. Removal of
      cell surface HA or inhibition of monocyte interaction with HA using antibody to
      CD44 prevented this effect of BMP-7. These data suggest that BMP-7 enhances HA
      dependent binding and reduces ICAM-dependent binding, which is known to stimulate
      TGF-beta1 synthesis. This hypothesis was examined further by stimulation of PTC
      ICAM expression by TNF-alpha. After TNF-alpha stimulation, monocyte-dependent TGF
      beta1 synthesis increased. This was abrogated by inhibition of ICAM-CD18
      interactions. TNF-alpha stimulation alone did not increase TGF-beta1 synthesis.
      TNF-alpha stimulation of PTC in the presence of BMP-7 failed to increase monocyte
      dependent TGF-beta1 stimulation. Although stimulation of PTC by BMP-7 alone
      decreased cell surface ICAM expression, it did not affect TNF-alpha-induced ICAM
      expression. The effect of BMP-7 on TGF-beta1 synthesis in TNF-alpha-stimulated
      cells was abrogated by disruption of CD44-HA interactions, suggesting that it was
      due to increased monocyte binding to HA on the cell surface.

PMID- 15574512
TI  - Glomerular plasmin-like activity in relation to nephritis-associated plasmin
      receptor in acute poststreptococcal glomerulonephritis.
AB  - A nephritogenic antigen for acute poststreptococcal glomerulonephritis (APSGN)
      was isolated recently from group A streptococcus and termed nephritis-associated
      plasmin receptor (NAPlr). In vitro experimental data indicate that the pathogenic
      role of NAPlr occurs through its ability to bind to plasmin and maintain its
      proteolytic activity. However, the mechanism whereby this antigen induces
      glomerular damage in vivo has not been fully elucidated. Renal biopsy tissues
      from 17 patients with APSGN, 8 patients with rapidly progressive
      glomerulonephritis, and 10 normal kidneys were analyzed in this study. Plasmin
      like activity was assessed on cryostat sections by in situ zymography with a
      plasmin-sensitive synthetic substrate. Serial sections were simultaneously
      assessed for NAPlr deposition by immunofluorescence staining. Glomerular plasmin
      like activity was absent or weak in normal controls and in patients with rapidly
      progressive glomerulonephritis, although tubulointerstitial activity was
      occasionally detected. Prominent glomerular plasmin-like activity was found in
      patients who had APSGN and in whom glomerular NAPlr was positive, whereas it was
      absent or weak in patients who had APSGN and in whom glomerular NAPlr was
      negative. The distribution of glomerular plasmin-like activity was identical to
      that of NAPlr deposition but was generally different from that of fibrin(ogen)
      deposition as assessed by double staining. The activity was abolished by the
      addition of aprotinin to the reaction mixture but was not altered by the addition
      of a matrix metalloprotease inhibitor, a cysteine protease inhibitor, or
      inhibitors of plasminogen activators. Thus, upregulated glomerular plasmin-like
      activity in relation to NAPlr deposition in APSGN was identified. This result
      supports the nephritogenic character of NAPlr and offers insight into the
      mechanism whereby this antigen induces nephritis.

PMID- 15574513
TI  - Connective tissue growth factor expressed in tubular epithelium plays a pivotal
      role in renal fibrogenesis.
AB  - Connective tissue growth factor (CTGF) is one of the candidate factors that are
      thought to mediate the downstream profibrotic action of TGF-beta. However, its
      precise role in renal interstitial fibrogenesis has not yet been clarified. It
      was demonstrated previously that CTGF was expressed in tubular epithelial cells
      that had been engulfed by interstitial fibrosis in the remnant kidney of the
      subtotal nephrectomy (SNx) model. In the present study, co-cultures of tubular
      epithelial cells (mProx24) and tubulointerstitial fibroblasts (TFB) that mimic
      the subepithelial mesenchyme in the kidney were used to study the profibrotic
      effects of TGF-beta1-induced CTGF. In these co-cultures, TGF-beta1 treatment
      resulted in significantly increased mRNA levels of type I collagen and
      fibronectin in the TFB. These effects were both direct and indirect, with the
      latter being mediated by CTGF derived from the co-cultured mProx24. Then TGF
      beta1 transgenic mice were subtotally nephrectomized and treated with CTGF
      antisense oligodeoxynucleotide, and their kidneys were analyzed for fibrosis.
      Intravenous administration of CTGF antisense oligodeoxynucleotide significantly
      blocked CTGF expression in the proximal tubular epithelial cells in the remnant
      kidney of these animals despite the sustained level of TGF-beta1 mRNA. This
      reduction in CTGF mRNA level paralleled a reduction in mRNA levels of matrix
      molecules as well as proteinase inhibitors plasminogen activator inhibitor-1 and
      tissue inhibitor of metalloproteinase-1, suppressing renal interstitial
      fibrogenesis. In conclusion, tubular CTGF acts as a downstream mediator of the
      profibrotic effects of TGF-beta1 in the remnant kidney, which is a promising
      target for antifibrotic drugs designed to treat TGF-beta1-dependent interstitial
      fibrosis.

PMID- 15574514
TI  - A pre-tRNA carrying intron features typical of Archaea is spliced in yeast.
AB  - Archaeal pre-tRNAs are characterized by the presence of the bulge-helix-bulge
      (BHB) structure in the intron stem-and-loop region. A chimeric pre-tRNA was
      constructed bearing an intron of the archaeal type and the mature domain of the
      Saccharomyces cerevisiae suppressor SUP4 tRNA(Tyr). This pre-tRNA(ArchEuka) is
      correctly cleaved in several cell-free extracts and by purified splicing
      endonucleases. It is also cleaved and ligated in S. cerevisiae cells, providing
      efficient suppression of nonsense mutations in various genes.

PMID- 15574515
TI  - Fast formation of the P3-P7 pseudoknot: a strategy for efficient folding of the
      catalytically active ribozyme.
AB  - Formation of the P3-P7 pseudoknot structure, the core of group I ribozymes,
      requires long-range base pairing. Study of the Tetrahymena ribozyme appreciates
      the hierarchical folding of the large, multidomain RNA, in which the P3-P7 core
      folds significantly slower than do the other domains. Here we explored the
      formation of the P3-P7 pseudoknot of the Candida ribozyme that has been reported
      to concertedly fold to the catalytically active structure with a rate constant of
      2 min(-1). We demonstrate that pseudoknot formation occurs during the rapid
      ribozyme compaction, coincident with formation of many tertiary interactions of
      the ribozyme. A low physiological concentration of magnesium (1.5 mM) is
      sufficient to fully support the pseudoknot formation. The presence of nonnative
      intermediates containing an unfolded P3-P7 region is evident. However, catalysis
      based analysis shows these nonnative intermediates are stable and fail to convert
      to the catalytically active structure, suggesting that rapid pseudoknot formation
      is essential for folding of the active ribozyme. Interestingly, RNAstructure
      predicts no stable Alt P3 structure for the Candida ribozyme, but two stable Alt
      P3s for the Tetrahymena ribozyme, explaining the dramatic difference in folding
      of the P3-P7 core of these two ribozymes. We propose that rapid formation of the
      P3-P7 pseudoknot represents a folding strategy ensuring efficient production of
      the catalytically active structure of group I ribozymes, which sheds new light on
      the mechanism of effective ribozyme folding in vivo.

PMID- 15574516
TI  - Uncoupling of RNAi from active translation in mammalian cells.
AB  - Small inhibitory RNAs (siRNAs) are produced from longer RNA duplexes by the RNAse
      III family member Dicer. The siRNAs function as sequence-specific guides for RNA
      cleavage or translational inhibition. The precise mechanism by which siRNAs
      direct the RNA-induced silencing complex (RISC) to find the complementary target
      mRNA remains a mystery. Some biochemical evidence connects RNAi with translation
      making attractive the hypothesis that RISC is coupled with the translational
      apparatus for scanning mRNAs. Such coupling would facilitate rapid alignment of
      the siRNA antisense with the complementary target sequence. To test this
      hypothesis we took advantage of a well-characterized translational switch
      afforded by the ferritin IRE-IRP to analyze RNAi mediated cleavage of a target
      mRNA in the presence and absence of translation. Our results demonstrate that
      neither active translation nor unidirectional scanning is required for siRNA
      mediated target degradation. Our findings demonstrate that nontranslated mRNAs
      are highly susceptible to RNAi, and blocking scanning from both the 5' and 3'
      ends of an mRNA does not impede RNAi. Interestingly, RNAi is about threefold more
      active in the absence of translation.

PMID- 15574517
TI  - Reconstitution in cultured cells of replicating HDV RNA from pairs of less than
      full-length RNAs.
AB  - The genome of hepatitis delta virus (HDV) is a small single-stranded circular RNA
      that is replicated via RNA-directed RNA synthesis. This makes use of a host RNA
      polymerase, probably pol II, that normally transcribes DNA templates. In vivo,
      the host polymerase can initiate replication from transfected linear RNAs using
      intramolecular template-switching. The present studies report that the polymerase
      could also achieve intermolecular switching leading to "reconstitution" of full
      length HDV RNAs following transfection with two linear RNAs that were less than
      full length and yet lacking different regions of the genome. These two RNAs were
      synthesized in vitro, gel purified, pre-annealed, and then transfected into
      delta293, a cell line conditionally expressing the small delta antigen that is
      essential for HDV replication. Northern analyses of total RNA harvested from
      transfected cells detected the accumulation of full-length HDV genomic and
      antigenomic RNAs. Such reconstitution of full-length replicating HDV RNA was also
      achieved using nine other pairs of antigenomic RNAs and three pairs of genomic
      RNAs. Annealing of the RNAs prior to transfection was required for detectable HDV
      reconstitution. A second cell line, Huh7, also supported reconstitution when a
      pair of RNAs was cotransfected together with mRNA for the small delta protein.
      Taken together, these results support a model that observed genome reconstitution
      is a special form of recombination involving intermolecular template switches and
      they provide insights into the mechanism of RNA-directed RNA transcription
      catalyzed by a host RNA polymerase.

PMID- 15574518
TI  - The 3'-untranslated region of cytochrome oxidase II mRNA functions in RNA editing
      of African trypanosomes exclusively as a cis guide RNA.
AB  - RNA editing in trypanosomes is a post-transcriptional process responsible for
      correcting the coding sequences of many mitochondrial mRNAs. Uridines are
      specifically added or deleted from mRNA by an enzymatic cascade in which a pre
      edited mRNA is specifically cleaved, uridines are added or removed, and the
      corrected mRNA is ligated. The process is directed by RNA molecules, termed guide
      RNAs (gRNA). The ability of this class of small, noncoding RNA to function in RNA
      editing is essential for these organisms. Typically, gRNAs are transcribed
      independent of the their cognate mRNA and anneal to form a binary RNA complex .
      An exception for this process may be cytochrome oxidase subunit II (COII) mRNA
      since a gene encoding a trans acting gRNA has not been identified. Using an in
      vitro editing assay we find that the 3' UTR of COII, indeed, functions as a guide
      for both the site and number of uridines added to the coding region of the COII
      mRNA. We further show that the guiding sequence within the COII 3' UTR can only
      function in COII editing when contiguous with the editing substrate, indicating
      that the 3' UTR of COII lacks sequence or structure information necessary to
      function as a trans-acting gRNA. While other RNAs have been shown to "guide" RNA
      processing reactions, our discovery that the COII 3' UTR directs editing of its
      cognate mRNA in cis, is a unique function for a 3' UTR. The findings described
      here have led us to propose a new model for the evolution of gRNAs in
      kinetoplastids.

PMID- 15574520
TI  - Yes, you can take it with you! Transfer of learning: from workshop to workplace.

PMID- 15574519
TI  - Domain structure and three-dimensional model of a group II intron-encoded reverse
      transcriptase.
AB  - Group II intron-encoded proteins (IEPs) have both reverse transcriptase (RT)
      activity, which functions in intron mobility, and maturase activity, which
      promotes RNA splicing by stabilizing the catalytically active RNA structure. The
      LtrA protein encoded by the Lactococcus lactis Ll.LtrB group II intron contains
      an N-terminal RT domain, with conserved sequence motifs RT1 to 7 found in the
      fingers and palm of retroviral RTs; domain X, associated with maturase activity;
      and C-terminal DNA-binding and DNA endonuclease domains. Here, partial
      proteolysis of LtrA with trypsin and Arg-C shows major cleavage sites in RT1, and
      between the RT and X domains. Group II intron and related non-LTR retroelement
      RTs contain an N-terminal extension and several insertions relative to retroviral
      RTs, some with conserved features implying functional importance. Sequence
      alignments, secondary-structure predictions, and hydrophobicity profiles suggest
      that domain X is related structurally to the thumb of retroviral RTs. Three
      dimensional models of LtrA constructed by "threading" the aligned sequence on X
      ray crystal structures of HIV-1 RT (1) account for the proteolytic cleavage
      sites; (2) suggest a template-primer binding track analogous to that of HIV-1 RT;
      and (3) show that conserved regions in splicing-competent LtrA variants include
      regions of the RT and X (thumb) domains in and around the template-primer binding
      track, distal regions of the fingers, and patches on the protein's back surface.
      These regions potentially comprise an extended RNA-binding surface that interacts
      with different regions of the intron for RNA splicing and reverse transcription.

PMID- 15574521
TI  - Health literacy: what the issue is, what is happening, and what can be done.

PMID- 15574522
TI  - State-level health policy to improve birth outcomes and reduce infant mortality.

PMID- 15574523
TI  - Public health informatics: the nature of the field and its relevance to health
      promotion practice.
AB  - The purpose of this article is to introduce the relatively new field of public
      health informatics and provide examples of how informatics is currently being
      applied to health promotion activities. Additionally, the article illustrates how
      informatics is well positioned to play a central role and is likely to be central
      to disease prevention, health education, and health promotion as it will be
      practiced in the future.

PMID- 15574525
TI  - A conceptual model of community capacity development for health promotion in the
      Alberta Heart Health Project.
AB  - PURPOSE: The objective of this study was to derive a conceptual model of
      community capacity development for health promotion based on the 5-year
      demonstration phase of the Alberta Heart Health Project. METHOD: Community
      actions associated with successful implementation and uptake of initiatives in
      four diverse target sites were identified by case study evaluation. RESULTS:
      Thirteen common elements of capacity development were found across the projects
      and categorized to define three primary dimensions of the process: (a) leadership
      that provided a driving force for implementation, (b) policy making that ensured
      diffusion and sustainability, and (c) use of local community resources and
      infrastructure. A conceptual model was constructed using these 3 dimensions and
      their interactions. CONCLUSION: Effective implementation of community health
      initiatives to promote heart health can be conceptualized as the involvement of
      local leadership, policy advocacy, and enhancement of existing infrastructure.
      The model highlights building these dimensions of community capacity development
      for health promotion.

PMID- 15574526
TI  - A review and synthesis of research evidence for self-efficacy-enhancing
      interventions for reducing chronic disability: implications for health education
      practice (part I).
AB  - Disability and poor quality of life attributable to chronic diseases such as
      arthritis, diabetes, and heart disease constitute challenging public health
      problems for American society. In the absence of any effective cure for these
      conditions, the secondary prevention of complications and improving quality of
      life and functional capacity through better disease self-management becomes
      critical and are key objectives of Healthy People 2010. The organizing focus of
      such disease self-management should be on improving coping, communication, and
      control by enhancing self-efficacy. Part I of this two-part article describes the
      common clinical features of chronic diseases and the diverse disease management
      strategies used for alleviating pain and preventing disability associated with
      these and reviews the role of self-efficacy as a theoretical framework for
      successful self-management interventions. Part II identifies and synthesizes the
      key research evidence for educational interventions designed to enhance
      individual self-efficacy perceptions and presents implications for practice in
      patient education.

PMID- 15574527
TI  - Sustainability of the impact of a public health intervention: lessons learned
      from the laval walking clubs experience.
AB  - To inform health promotion practice regarding the sustainability of public health
      interventions, the authors interviewed the directors of 13 new community-based
      organizations created through a practitioner-initiated public health intervention
      designed to promote physical activity at the community level. The purpose of the
      interviews was to uncover the factors that lead organization directors to become
      involved in the initiative and to maintain their involvement across an extended
      period of time. Results showed that there were 3 categories of positive outcomes
      associated with leading a walking club: maintaining and improving health,
      personal satisfaction, and group motivation. Difficulties associated with
      directing the club included high participant turnover rates, isolation of club
      directors, and lack of support from community organizations. Club directors
      indicated that sustainability would be enhanced through developing individual
      competencies, becoming more proficient at leading group dynamics, and developing
      better rootedness in the community. This information is interpreted in light of
      the six factors associated with sustainability.

PMID- 15574528
TI  - Using photography to cross generational, linguistic, and cultural barriers to
      develop useful survey instruments.
AB  - Photographs are used as a research tool by anthropologists and as a technique to
      empower special populations, advocacy groups, and policy makers. This case
      describes how photography was used to develop a survey to study alcohol
      expectancies among Thai adolescents. A multi-cultural research team faced
      generational, linguistic, and cultural barriers in understanding Thai adolescent
      alcohol use well enough to write useful questions about alcohol expectancies.
      Asking adolescents to take and then discuss their photographs about alcohol
      allowed them to express themselves without the imposition of an organizational
      framework by the investigators. Group discussions of the photographs revealed
      nuances and subtleties of interpretation of behavior and expectancies involving
      alcohol that might otherwise have not emerged. The results of this activity were
      used to refine an expectancy scale used in a large-scale survey of alcohol
      expectancies and use.

PMID- 15574529
TI  - Environmental perceptions related to physical activity in high- and low-risk
      counties.
AB  - To identify whether perceptions about the physical activity environment were
      related to the prevalence of sedentary lifestyle, residents from high-risk (n =
      153) or low-risk (n = 100) counties were interviewed. County risk status was
      determined by the prevalence of cardiovascular mortality, overweight, and
      sedentary lifestyle. Key public officials in the same counties were also
      interviewed. Residents in the low-risk county were more likely to report having
      sidewalks in their community and that these sidewalks were safe and well lit than
      residents living in the high-risk counties. Low-risk county residents also
      reported more indoor recreation facilities being available than the residents in
      the high-risk counties. Residents supported allocating tax dollars toward
      improving sidewalks, lighting, and so on. Thus a more conducive environment for
      physical activity was found in the low-risk county. Improving physical
      environments and individual perceptions could help increase physical activity
      behavior.

PMID- 15574530
TI  - Unpacking the black box: a deconstruction of the programming approach and
      physical activity interventions implemented in the Kahnawake Schools Diabetes
      Prevention Project.
AB  - An ecological lens was used to deconstruct the programming approach and unpack
      physical activity interventions implemented through the Kahnawake Schools
      Diabetes Prevention Project. Despite a surge of interest in ecologically based
      health promotion programming, optimal combinations of interventions and
      programming approaches to promote community physical activity involvement have
      not been systematically studied. The authors obtained physical activity
      intervention descriptions through archive retrieval and face-to-face interviews
      with intervention staff. Programming approach, intervention targets, strategies
      for change, and delivery settings were assessed by applying the intervention
      analysis procedure to intervention descriptions. A complex intervention package
      was found containing a host of multitarget, multisetting intervention strategies
      designed and implemented through dynamic exchanges between a diversity of
      community partners. This study provides a first step toward better understanding
      community intervention packages and programming strategies for promoting physical
      activity involvement within a community setting.

PMID- 15574531
TI  - Promoting "dual protection" from pregnancy and sexually transmitted disease: a
      social ecological approach.
AB  - High rates of unintended pregnancy and sexually transmitted disease in women
      challenge health promotion to identify improvements in "dual protection"
      interventions. Findings from an exploratory qualitative study using a social
      ecological model identify causal, contextual, and intervening factors that
      influence dual protection. The study examined 48 U.S. women completing a sexually
      transmitted disease clinic process and focused on women at high risk of unwanted
      pregnancy and sexually transmitted disease. We frame findings from these
      interviews using social ecology to illustrate the levels where intervention to
      promote the concept of dual protection and associated behaviors might occur.
      Presenting findings within this framework offer an understanding of complex
      factors that influence dual protection and also present an opportunity to
      consider strategies for promoting dual protection that include interventions at
      the structural/environmental level, the social/interpersonal level, and the
      individual level.

PMID- 15574532
TI  - Development and use of a tool for assessing sidewalk maintenance as an
      environmental support of physical activity.
AB  - The importance of regular physical activity is well documented, yet according to
      epidemiological surveillance data, physical inactivity among all age groups
      persists. Past attempts to promote physical activity focused on individual-level
      changes; current approaches focus on environmental changes that will provide
      opportunities for whole communities to be active. The current ecological focus
      has led to an increase in funding and research regarding environmental supports
      of physical activity. As this is a new area of research, much work needs to be
      done to improve the ability to assess environmental features that support
      physical activity. This article describes a partnership between researchers and
      community members to develop and test an objective tool to measure sidewalk
      maintenance. Community members used data collected with the tool to increase
      awareness about sidewalk maintenance issues among local policy makers.
      Collaboration between researchers and community partners was critical for the
      success of this study.

PMID- 15574533
TI  - Assessment of public health educator practice: health educator responsibilities.
AB  - This study presents a method for better understanding how practicing health
      educators in local health departments spend their time. The purpose of this study
      was to document the daily practice of health educators in the 10 areas of
      responsibility as defined by a competency-based framework for graduate-level
      health educators. The results of the current study present the average percentage
      of time health educators spent carrying out each area of responsibility and the
      percentage of health educators that did not carry out activities related to a
      specific area of responsibility. For example, the greatest percentage of time was
      spent implementing programs (21.2%), and approximately 60% of the health
      educators in the sample did not conduct research nor did they participate in
      activities to advance the profession. These findings have implications for the
      professional preparation of health educators and for their continuing education.
      The current study contains several suggestions for future research in this area.

PMID- 15574534
TI  - Assessment of the training needs of Kentucky public health educators.
AB  - A survey to identify the training needs of Kentucky public health educators was
      conducted during the spring of 2001. Questionnaire items assessed respondents'
      job title, years of experience in public health education, percentage of work
      time doing public health education, and educational background. Respondents were
      asked to rate their perceived level of mastery of 50 public health educator
      competencies and skills, desire for additional training in each of the
      competencies and skills, and preferred format for training. Surveys were mailed
      to 699 health department employees across the commonwealth. A total of 366
      questionnaires were completed and returned. Results provide a descriptive profile
      of Kentucky public health educators and pinpoint competency deficiencies. Grant
      writing, budgeting, evaluation, managing controversy, and multicultural
      understanding were identified most frequently as competencies in which more
      training was needed. An overview of survey results and recommendations regarding
      the training of Kentucky public health educators is provided.

PMID- 15574535
TI  - Telephone support for pregnant smokers who want to stop smoking.
AB  - This article describes a statewide, proactive telephone peer-support system to
      help low-income pregnant women stop smoking. From October 1994 to December 2000,
      948 pregnant smokers attending the Women, Infants, Children program accepted an
      offer to receive support by telephone from a woman ex-smoker who called weekly,
      biweekly, and then monthly to provide guidance, encouragement, and reinforcement
      for smoking cessation. This free service, funded by the Vermont Department of
      Health, resulted in 25% self-reported abstinence at last telephone contact when
      women never reached for telephone support were counted as smokers, and self
      reported abstinence during pregnancy of 20% among participants who returned for
      their postpartum Women, Infants, Children visit. These findings suggest that
      proactive telephone peer support is a viable way to help pregnant women stop
      smoking during pregnancy.

PMID- 15574536
TI  - Establishing an Internet-based tobacco-control network for Czech health
      professionals.
AB  - This article describes the background, implementation, and evaluation of an
      Internet-based health promotion network in the Czech Republic. The network was
      intended to build the indigenous capacity of Czech health professionals in the
      use of the Internet for tobacco control to organize and coordinate public health
      campaigns, heighten public awareness, and catalyze policy change. Multiple
      methods of evaluation included three needs assessment surveys, three training
      workshop evaluations, an Internet survey of participating member organizations,
      and quarterly reports from the project partners. The evaluation showed that an
      Internet-based network was established with 40 health professionals from 30
      organizations. A grassroots heart disease prevention and tobacco-control advocacy
      group was formed. Network participants utilized and continue to utilize the
      Internet to communicate, research, coordinate outreach, and advocate tobacco
      control issues.

PMID- 15574537
TI  - Burns.

PMID- 15574538
TI  - Pneumococcal infections.

PMID- 15574539
TI  - Chronic steroid and immunosuppressant therapy in children.

PMID- 15574540
TI  - Index of suspicion.

PMID- 15574541
TI  - Question from the clinician: colic in nonhumans.

PMID- 15574542
TI  - Postoperative cognitive dysfunction: aprotinin, bleeding and cognitive testing.

PMID- 15574543
TI  - Changing practice in airway management: are we there yet?

PMID- 15574544
TI  - A high initial VAS score and sedation after iv morphine titration are associated
      with the need for rescue analgesia.
AB  - PURPOSE: Administration of sc morphine has been recommended two hours after the
      end of iv morphine titration in the postanesthesia care unit (PACU), but in some
      cases patients complain of pain earlier than this. We assessed pain after the end
      of iv morphine titration and studied the characteristics of patients who needed
      rescue sc morphine. METHODS: Postoperative pain was assessed using the visual
      analogue scale (VAS; 0 to 100) and the threshold required to administer morphine
      in the PACU was a score of 30. VAS was measured every 15 min up to two hours
      after the end of iv morphine titration. Patients were divided into two groups,
      those who required sc morphine before two hours and those who did not. Data are
      expressed as mean +/- SD or odds ratio (OR; 95% confidence interval). RESULTS:
      Four hundred and two patients were analyzed. Mean age was 51 +/- 19 yr, initial
      VAS 69 +/- 19, and the dose of iv morphine 11.7 +/- 6.6 mg. The number of
      patients requiring sc morphine within two hours was 84 (21%). These patients had
      more severe initial postoperative pain (73 +/- 20 vs 68 +/- 19, P < 0.05), and
      experienced sedation more frequently during morphine titration (45 vs 25%, P <
      0.001). Using a multivariate analysis, occurrence of sedation during titration
      [OR 2.3 (1.4-3.8), P < 0.001] and an initial pain score > or = 60 [OR 1.9 (1.0
      3.4), P < 0.05] were significantly associated with the need for rescue sc
      morphine. CONCLUSION: Sedation during titration and an initial VAS > or = 60 are
      characteristics of the patients who require rescue (less than two hours) sc
      morphine after iv morphine titration.

PMID- 15574545
TI  - Non-narcotic adjuvants may improve the duration and quality of analgesia after
      knee arthroscopy: a brief review.
AB  - PURPOSE: We have evaluated randomized controlled trials of the administration of
      clonidine, neostigmine, steroids and non-steroidal anti-inflammatory agents intra
      articularly as adjuvants to local anesthetic drugs after arthroscopic knee
      surgery. METHODS: Twenty-five studies were reviewed using specific inclusion
      criteria and, accordingly, included in the final assessment. These studies were
      assessed for pain scores, total analgesic consumption and time to first analgesic
      request to determine a possible peripheral effect, as opposed to possible
      systemic effects of an adjuvant administered intra-articularly. RESULTS: A total
      of 16 studies, met the inclusion criteria. These studies considered the use of
      non-steroidal anti-inflammatory drugs, steroids, neostigmine and clonidine.
      Ketorolac was used in four studies (for a total of 230 patients) and showed a
      significant improvement in analgesia. Clonidine has shown considerable analgesic
      effect, with minimal adverse effects. All seven studies assessed in this review
      were supportive (a total of 424 patients). Furthermore the addition of clonidine
      to bupivacaine or morphine was found to increase duration and quality of
      postoperative analgesia. CONCLUSIONS: Current evidence indicates that a variety
      of agents have synergistic effects when added to local anesthetics and there is
      evidence that the improvement in analgesia is, at least partially, through a
      local rather than a central mechanism. The results of this review suggest that
      clonidine and ketorolac, when administered intra-articulary after arthroscopic
      knee surgery, may reduce postoperative pain.

PMID- 15574546
TI  - The vascular relaxing effects of sevoflurane and isoflurane are more important in
      hypertensive than in normotensive rats.
AB  - PURPOSE: The vascular response to anesthetics is altered in hypertensive patients
      since the functional and structural integrities of vascular smooth muscle and
      endothelium are deranged. The effects of anesthetics on angiotensin II (Ang II)
      induced changes in vascular tone are not well understood. We investigated the
      effects of sevoflurane and isoflurane on Ang II-induced vasoconstriction in
      spontaneously hypertensive rats (SHR). METHODS: The dose-dependent effects of
      sevoflurane and isoflurane on the Ang II-induced contraction of aortic rings, in
      the presence and absence of an intact endothelium, were investigated in
      normotensive Wistar-Kyoto rats (WKY) and SHR and compared using isometric force
      transducers. RESULTS: Ang II (10(-9)-10(-6) M) induced a similar transient phasic
      contraction of endothelium-intact rings from the two rat strains in a dose
      dependent manner. Removal of the endothelium augmented the Ang II-elicited phasic
      contraction, to a greater extent in the SHR group than in the WKY group.
      Sevoflurane and isoflurane (1-3 minimum alveolar concentration) concentration
      dependently inhibited the Ang II-induced contraction of endothelium-intact rings
      from WKY; an effect that was greatly enhanced following removal of the
      endothelium. A greater degree of attenuation of the Ang II-induced contraction of
      both endothelium-intact and -denuded rings by the two anesthetics was observed in
      the SHR group. The inhibitory effects of isoflurane on the Ang II-induced
      contraction of aortic rings from both strains appeared to be stronger than that
      of sevoflurane at equipotent concentrations. CONCLUSION: Our finding that the
      inhibitory effects of isoflurane and sevoflurane on Ang II-induced
      vasoconstriction are enhanced in SHR may, at least in part, account for the
      anesthesia-induced systemic hypotension frequently seen in hypertensive patients.

PMID- 15574547
TI  - Preemptive gabapentin decreases postoperative pain after lumbar discoidectomy.
AB  - PURPOSE: We investigated whether the preemptive use of gabapentin, a structural
      analogue of gamma amino butyric acid could reduce postoperative pain and fentanyl
      consumption in patients after single-level lumbar discoidectomy. METHODS: Fifty
      six ASA I and II patients were randomly allocated into two equal groups to
      receive either gabapentin 300 mg or placebo two hours before surgery. After
      surgery, the pain was assessed on a visual analogue scale (VAS) at intervals of 0
      6, 6-12, 12-18, and 18-24 hr at rest. Total fentanyl consumption in the first 24
      hr after surgery was also recorded. Fentanyl 2 mug.kg(-1) intravenously was used
      to treat postoperative pain on patients' demand. RESULTS: Patients in the
      gabapentin group had significantly lower VAS scores at all time intervals of 0-6,
      6-12, 12-18, and 18-24 hr than those in the placebo group (3.5 +/- 2.3, 3.2 +/-
      2.1, 1.8 +/- 1.7, 1.2 +/- 1.3 vs 6.1 +/- 1.7, 4.4 +/- 1.2, 3.3 +/- 1.1, 2.1 +/-
      1.2; P < 0.05). The total fentanyl consumed after surgery in the first 24 hr in
      the gabapentin group (233.5 +/- 141.9, mean + SD) was significantly less than in
      the placebo group (359.6 +/- 104.1; P < 0.05). CONCLUSION: Preemptive gabapentin
      300 mg po significantly decreases the severity of pain postoperatively in
      patients who undergo single-level lumbar discoidectomy.

PMID- 15574548
TI  - A new guidance device facilitates percutaneous puncture of the foramen ovale in
      human cadavers.
AB  - PURPOSE: Trigeminal neuralgia is the most common neurological cause for facial
      pain. Contemporary interventional treatment relies on surgical microvascular
      decompression or, alternatively, percutaneous interventions targeting the
      semilunar ganglion via the foramen ovale. For the latter approach, only free-hand
      punctures using fluoroscopy devices have been reported. Therefore, the present
      study aimed to evaluate a new fluoroscopy-based guidance device for
      transforaminal puncture. METHODS: Two experienced examiners punctured the foramen
      ovale bilaterally free-hand, and using a guidance device in human cadavers (n =
      9). The number of attempts for puncture was recorded. A new attempt was counted
      each time the needle had to be retracted for redirection. RESULTS: As compared to
      the free-hand puncture of the foramen ovale (4.44 +/- 2.79), the new guidance
      device significantly reduced the number of trials needed (1.37 +/- 0.69).
      CONCLUSION: The employment of a guidance device facilitated percutaneous
      transforaminal puncture and resulted in a significantly decreased number of
      puncture attempts as compared to free-hand techniques in human cadavers.

PMID- 15574549
TI  - Spinal anesthesia for Cesarean section in a parturient with long QT syndrome.
AB  - PURPOSE: To report the first use of spinal anesthesia for Cesarean section (CS)
      in a parturient with a long QT syndrome (LQTS) and an automatic implantable
      cardiac defibrillator (AICD). Although both general and epidural anesthesia have
      been described for CS in patients with LQTS, there are no previous case reports
      on the use of spinal anesthesia. The clinical features, diagnosis, treatment and
      anesthetic management of LQTS are discussed. CLINICAL FEATURES: A 31-yr-old
      woman, gravida 2 para 1 known to have LQTS and an AICD, presented in labour at 35
      weeks gestation, three weeks before her scheduled CS. Her previous delivery by CS
      under spinal anesthesia at our institution was uneventful. On this occasion, we
      elected to administer spinal anesthesia because she was asymptomatic (no
      arrhythmia or cardiac arrest) for the last few years, was hemodynamically stable,
      and had received uneventful spinal anesthesia before. CONCLUSION: Spinal
      anesthesia was used safely for CS in this parturient with LQTS.

PMID- 15574550
TI  - The Microcuff tube allows a longer time interval until unsafe cuff pressures are
      reached in children.
AB  - PURPOSE: To compare cuff pressures during nitrous oxide exposure in the new
      Microcuff pediatric tracheal tube (MPT) with ultrathin high volume - low pressure
      polyurethane cuff to a tube with a standard polyvinyl chloride (PVC) cuff.
      METHODS: With approval of the local Ethics Committee, 30 pediatric patients
      requiring tracheal intubation [tube size internal diameter (ID) 4.0 mm, or ID 7.0
      mm) were included. Patients were randomly divided in three groups: A) MPT,
      baseline cuff pressure 20 cm H(2)O; B) PVC, baseline cuff pressure 20 cm H(2)O;
      and C) MPT, baseline cuff pressure set to sealing pressure. Anesthesia technique
      and ventilator settings were standardized. The time required for cuff pressure to
      increase to 25 cm H(2)O was recorded and pressure reduced to baseline. The number
      of gas removals required during the first hour was noted. Data are median
      (range). Groups were compared by the Kruskal-Wallis test (P < 0.05). RESULTS:
      There were no differences between groups in patient characteristics. PVC and MPT
      cuffs inflated to a baseline pressure of 20 cm H(2)O were similar regarding the
      time to first removal of gas [A: nine minutes (4-24), B: eight minutes (4-46)],
      and number of removals required [A: four (2-6), B: three (1-5)]. In MPT with
      baseline pressure set to sealing pressure [10 cm H(2)O (8-14)] time to first gas
      removal and number of removals were significantly less (P < 0.05). CONCLUSION:
      When baseline inflation pressure was set at 20 cm H(2)O, cuff pressure increased
      similarly in MPT and PVC tubes. When inflated just to sealing pressure, the MPT
      allowed a longer time interval until the upper limit of 25 cm H(2)O was reached.

PMID- 15574551
TI  - Aprotinin decreases the incidence of cognitive deficit following CABG and
      cardiopulmonary bypass: a pilot randomized controlled study.
AB  - PURPOSE: Cognitive deficit after coronary artery bypass surgery (CABG) has a high
      prevalence and is persistent. Meta-analysis of clinical trials demonstrates a
      decreased incidence of stroke after CABG when aprotinin is administrated
      perioperatively. We hypothesized that aprotinin administration would decrease the
      incidence of cognitive deficit after CABG. METHODS: Thirty-six ASA III-IV
      patients undergoing elective CABG were included in a prospective, randomized,
      single-blinded pilot study. Eighteen patients received aprotinin 2 x 10(6) KIU
      (loading dose), 2 x 10(6) KIU (added to circuit prime) and a continuous infusion
      of 5 x 10(5) KIU.hr(-1). A battery of cognitive tests was administered to
      patients and spouses (n = 18) the day before surgery, four days and six weeks
      postoperatively. RESULTS: Four days postoperatively new cognitive deficit
      (defined by a change in one or more cognitive domains using the Reliable Change
      Index method) was present in ten (58%) patients in the aprotinin group compared
      to 17 (94%) in the placebo group [95% confidence interval (CI) 0.10-0.62, P =
      0.005); (P = 0.01)]. Six weeks postoperatively, four (23%) patients in the
      aprotinin group had cognitive deficit compared to ten (55%) in the placebo group
      (95% CI 0.80-0.16, P = 0.005); (P = 0.05). CONCLUSION: In this prospective pilot
      study, the incidence of cognitive deficit after CABG and cardiopulmonary bypass
      is decreased by the administration of high-dose aprotinin.

PMID- 15574552
TI  - Images in Anesthesia: accidental knot formation of a pulmonary artery catheter.

PMID- 15574553
TI  - Isoflurane preserves central nervous system blood flow during intraoperative
      cardiac tamponade in dogs.
AB  - PURPOSE: The present study tested the hypothesis that the anesthetic technique
      will influence the changes in regional blood flow (RBF) during intraoperative
      cardiac tamponade. METHODS: Twenty-four dogs were divided into three equal
      groups: Group I, anesthesia was maintained with ketamine (25 mg.kg(-1).hr(-1));
      Group II, with fentanyl and midazolam (F-M; 10 mug.kg(-1).hr(-1) and 0.5 mg.kg(
      1).hr(-1), respectively); Group III with 1 minimum alveolar concentration (MAC;
      1.4%) isoflurane. Radioactive microspheres were used to measure RBF in
      myocardium, brain, spinal cord, abdominal viscera, skeletal muscle and skin.
      Cardiac output (CO) was measured by thermodilution and arterial pressure with a
      catheter situated in the thoracic aorta. Catheters were introduced into the
      pericardial cavity to infuse isotonic saline and to measure intrapericardial
      pressure (IPP). Measurements were obtained under control conditions and during
      tamponade, as defined by an increase in IPP sufficient to reduce mean arterial
      pressure by 40%. RESULTS: Tamponade caused decreases in CO and RBF that were
      comparable under the three anesthetics, except that RBF in subcortical regions of
      the brain and in the spinal cord were maintained under isoflurane but decreased
      under ketamine or F-M. CONCLUSIONS: In dogs, intraoperative cardiac tamponade
      caused comparable changes in RBF under the different anesthetic techniques except
      that autoregulation was effective in maintaining RBF within the central nervous
      system only under isoflurane anesthesia. Our findings provide no compelling
      reason to recommend one anesthetic over the others for maintenance of anesthesia
      in situations with increased risk for intraoperative cardiac tamponade. However,
      they cannot be extrapolated to anesthesia induction in the presence of cardiac
      tamponade.

PMID- 15574554
TI  - Use of the Laryngeal Tube in two unexpected difficult airway situations: lingual
      tonsillar hyperplasia and morbid obesity.
AB  - PURPOSE: The 2003 ASA Practice Guidelines for Management of the Difficult Airway
      suggest the early use of the Laryngeal Mask Airway and Combitube as rescue airway
      devices in the cannot ventilate-cannot intubate situation, switching the focus
      from laryngoscopy and intubation to ventilation and oxygenation. The Practice
      Guidelines are not intended as standards but as recommendations. Multiple new
      alternative airway devices were described in the last ten years. The Laryngeal
      Tube (LT) is a new Food and Drug Administration approved supraglottic airway
      device. The device is in use in Europe since 1999 and in the United States since
      2002. CLINICAL FEATURES: We report two cases in which the LT was used to solve
      two unexpected difficult airway situations. The first case ("cannot intubate
      inadequate mask ventilation") involved an undiagnosed lingual tonsillar
      hyperplasia and the LT provided the means to ventilate and administer the
      anesthetic. In the second case ("cannot ventilate-cannot intubate") we report the
      successful use of the LT to rescue the airway in a morbidly obese patient. In
      both cases an endotracheal tube was ultimately inserted using an awake fibreoptic
      technique with the patient in the sitting position. CONCLUSIONS: In these
      clinical situations of unexpected difficult airway with significant periglottic
      obstruction the LT provided adequate ventilation after the first insertion. The
      LT may complement the laryngeal mask airway in difficult airway management.
      Further research is needed to define the role of the LT in the management of
      difficult airways.

PMID- 15574555
TI  - Emergency gum elastic bougie-assisted tracheal intubation in four patients with
      upper airway distortion.
AB  - PURPOSE: The gum elastic bougie (GEB) has been in use for a long time and allows
      tracheal intubation in most cases of difficult direct laryngoscopy. Use of the
      GEB when anatomical landmarks of the upper airway are not recognizable has not
      been reported. We describe our experience of airway management with the GEB in
      cases of severe upper airway distortion. CLINICAL FEATURES: Four patients with
      severe respiratory distress caused by upper airway distortion secondary to
      various non-malignant causes were managed with the GEB. For these four patients,
      a rapid sequence induction of anesthesia was performed with a surgeon present
      during the procedure. The GEB was used as the initial intubating technique in all
      cases and allowed a rapid and successful tracheal intubation in spite of non
      recognizable anatomical structures. The distal hold-up feeling after GEB
      insertion confirmed, in all cases, the correct intratracheal position of the GEB.
      CONCLUSION: The GEB can be a valuable tool in cases of difficult airway
      management caused by upper airway distortion. The lack of visualization of normal
      pharyngeal structures did not prevent the successful insertion of the GEB in the
      trachea in the four patients reported.

PMID- 15574556
TI  - Central dexmedetomidine attenuates cardiac dysfunction in a rodent model of
      intracranial hypertension.
AB  - PURPOSE: To determine if central sympathetic blockade by dexmedetomidine, a
      selective alpha(2) adrenergic receptor agonist, prevents cardiac dysfunction
      associated with intracranial hypertension (ICH) in a rat model. METHODS:
      Following intracisternal administration of dexmedetomidine (1 microg.microL(-1),
      10 microL volume) or the stereoisomer levomedetomidine (1 microg.microL(-l), 10
      microL volume) in halothane-anesthetized rats, a subdural balloon catheter was
      inflated for 60 sec to produce ICH. Intracranial pressure, hemodynamic, left
      ventricular (LV) pressures and electrocardiographic (ECG) changes were recorded.
      Plasma and myocardial catecholamines and malondialdehyde (MDA) levels were
      measured. RESULTS: After levomedetomidine administration, subdural balloon
      inflation precipitated an increase in mean arterial pressure (149 +/- 33% of
      baseline), heart rate (122 +/- 19% of baseline), LV systolic pressure (LVP), LV
      end-diastolic pressure (LVEDP), LV developed pressure (LVDP), LV dP/dtmax and
      rate pressure product (RPP) (132 +/- 19%, 260 +/- 142%, 119 +/- 15%, 126 +/- 24%
      and 146 +/- 33% of baseline value, respectively). ICH decelerated LVP fall (tau),
      as tau increased from 7.75 +/- 1.1 to 14.37 +/- 4.5 msec. Moreover, plasma
      norepinephrine levels were elevated (169 +/- 50% of baseline) and there was the
      appearance of cardiac dysrhythmias and other ECG abnormalities. This response was
      transient and cardiac function deteriorated in a temporal manner. Intracisternal
      dexmedetomidine prevented the rise in plasma norepinephrine, blocked the ECG
      abnormalities, and preserved cardiac function. Moreover, dexmedetomidine
      attenuated the rise in MDA levels. CONCLUSIONS: The results demonstrate that
      dexmedetomidine attenuates cardiac dysfunction associated with ICH. Our results
      provide evidence for the role of central sympathetic hyperactivity in the
      development of cardiac dysfunction associated with ICH.

PMID- 15574557
TI  - DNR directives are established early in mechanically ventilated intensive care
      unit patients.
AB  - PURPOSE: Setting treatment goals in the intensive care unit (ICU) often involves
      resuscitation decisions. Our objective was to study the rate of establishing do
      not-resuscitate (DNR) directives, determinants, and outcomes of those directives
      for mechanically ventilated patients. METHODS: In a multicentre observational
      study, we included consecutive adults with no DNR directives within 24 hr of ICU
      admission who were mechanically ventilated for at least 48 hr. We identified the
      rate with which DNR directives were established, and factors associated with
      these directives. RESULTS: Among 765 patients, DNR directives were established
      for 231 (30.2%) patients; 143 (62.1%) of these were established within the first
      week. Factors independently associated with a DNR directive were: patient age [>
      or = 75 yr (hazard ratio [HR] 2.3, 95% confidence interval 1.5-3.4], 65 to 74 yr
      (HR 1.8, 1.2-2.7), 50 to 64 yr (HR 1.4, 1.0-2.2) relative to < 50 yr); medical
      rather than surgical diagnosis (HR 1.8, 1.3-2.5); multiple organ dysfunction
      score (HR 1.7 for each five-point increment, 1.4-2.0); physician prediction of
      ICU survival [< 10% (HR 15.0, 6.7-33.6)], 10 to 40% [(HR 5.0, 2.3-11.2), 41 to
      60% (HR 4.0, 1.8-9.0) relative to > 90%]; and physician perception of patient
      preference to limit life support (no advanced life support [(HR 5.8, 3.6-9.4) or
      partial advanced life support (HR 3.2, 2.2-4.6) compared to full measures].
      CONCLUSION: One third of mechanically ventilated patients had DNR directives
      established early during their ICU stay after the first 24 hr of admission. The
      strongest predictors of DNR directives were physician prediction of low
      probability of survival, physician perception of patient preference to limit life
      support, organ dysfunction, medical diagnosis and age.

PMID- 15574558
TI  - Best evidence in critical care medicine: treatment: vasodilatation with
      nitroprusside in symptomatic patients with severe aortic stenosis and congestive
      heart failure improves cardiac index.

PMID- 15574559
TI  - Blood product use during orthotopic liver transplantation.

PMID- 15574560
TI  - Knotting of a peripherally inserted central catheter.

PMID- 15574561
TI  - Pretreatment with flurbiprofen axetil and venous occlusion to reduce pain during
      injection of propofol.

PMID- 15574562
TI  - Optimal dose range of epidural naloxone to reduce nausea in patients receiving
      epidural morphine.

PMID- 15574563
TI  - Central neural blockade in Charcot-Marie-Tooth disease.

PMID- 15574564
TI  - Dural sinus thrombosis in a late preeclamptic woman.

PMID- 15574565
TI  - Planned lightwand intubation in a patient with a known difficult airway.

PMID- 15574566
TI  - Lightwand intubation can improve airway management.

PMID- 15574567
TI  - Migration of the endotracheal tube during laparoscopy-assisted abdominal surgery
      in young and elderly patients.

PMID- 15574568
TI  - Another cause of obstruction of the endotracheal tube during laparoscopic
      cholecystectomy.

PMID- 15574569
TI  - Radiological evaluation of cerebral aneurysms in selected clinical presentations.
AB  - BACKGROUND AND PURPOSE: Cerebral aneurysms have different presenting features
      and, to some extent, a variable clinical course based on the pattern of
      subarachnoid hemorrhage, the circumstance of their discovery, and the anatomy.
      Thus, the neuroimaging workup must be tailored accordingly to provide accurate
      diagnosis and optimal follow-up. METHOD: The authors suggest neuroradiological
      evaluation of patients in the emergency room and in cases of perimesencephalic
      subarachnoid hemorrhage, aneurysmal pattern of subarachnoid hemorrhage with
      normal angiography, vascular infundibula, unruptured/incidental aneurysms,
      infectious aneurysms, dissecting aneurysms, dolichoectatic/fusiform aneurysms,
      intracavernous aneurysms, and traumatic aneurysms. CONCLUSION: Recent
      neuroimaging advances have contributed to improvement in diagnostic safety and
      accuracy, allowing a more diligent patient follow-up, improved patient outcome,
      and enhanced physician perception and clinical judgment.

PMID- 15574570
TI  - Atlas-based anatomic labeling in neurodegenerative disease via structure-driven
      atlas warping.
AB  - A new method is presented for the automated anatomic labeling and comparative
      morphometric analysis of brain magnetic resonance imaging, warping a prelabeled
      atlas into congruence with the subject anatomy. The strategy emphasizes
      anatomically meaningful atlas deformations in the presence of strong degeneration
      and substantial morphologic differences, for example, cases with high levels of
      atrophy. The atlas deformation is not driven by image intensity similarities but
      by continuous anatomic correspondence maps, derived from individual presegmented
      brain structures. Automatically generated correspondence maps provide large sets
      of fiducials, driving a warp with many thousand degrees of freedom. Validation
      included a scan-rescan study and anatomically relevant self-validation in
      multiple sclerosis patients with substantial cortical and subcortical
      degeneration. The mean coefficient of variation in the scan-rescan study was
      1.4%, with no significant difference in precision between normal and
      neurodegenerative anatomies. The self-validation demonstrated good structural
      overlap, with substantial improvement over established methods, such as Talairach
      spatial normalization.

PMID- 15574571
TI  - Reproducibility and accuracy of quantitative magnetic resonance imaging
      techniques of whole-brain atrophy measurement in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Whole-brain atrophy is of growing interest as an outcome
      measure in multiple sclerosis (MS) clinical trials. The authors compared the
      reproducibility and accuracy of 3 quantitative techniques of measurement in
      patients with MS. METHODS: Thirty-four patients with relapsing-remitting MS
      (median Expanded Disability Status Scale disability score = 1.5) were studied.
      Brain parenchymal fraction (BPF) was quantified on spin-echo 2-dimensional T1
      weighted axial 5-mm slice thickness sequences by semiautomated (Buffalo, Trieste)
      or automated (SIENAX) algorithms. RESULTS: Mean +/- SD BPFs were 0.830 +/- 0.04
      with Buffalo, 0.824 +/- 0.04 with Trieste, and 0.826 +/- 0.04 with SIENAX methods
      (P = nonsignificant [NS]). Mean BPF scan-rescan coefficient of variation (COV)
      was 0.41% for Buffalo, 0.44% for Trieste, and 0.32% for SIENAX (P =NS).The
      semiautomated methods showed higher accuracy than the automated method in brain
      extraction (masking; P = .001). The errors of skull stripping included scalp,
      skull bone marrow, inferior parts of temporal lobes anterior to the brain stem,
      face structures, sagittal sinuses, eyes, and optic nerves. Buffalo (r = -0.37, P
      = .034) and Trieste (r = -.36, P = .039) BPFs showed stronger cor relation with
      disability than SIENAX (r = -0.16, P = .219). These differences were
      statistically significant (P = .0031 for Buffalo and P = .0037 for Trieste BPF).
      CONCLUSIONS: This study showed a high reproducibility of both semiautomated and
      automated methods for brain atrophy measurement. The semiautomated methods showed
      higher accuracy than the automated SIENAX method did in the evaluation of brain
      extraction, especially in infratentorial and cortical regions, where operator
      interaction during the masking processes was essential.

PMID- 15574572
TI  - Outcomes in acute ischemic stroke patients without angiographically documented
      arterial occlusion.
AB  - BACKGROUND AND PURPOSE: Patients with acute ischemic stroke who undergo emergent
      cerebral angiography for consideration of intra-arterial treatment and do not
      have an angiographically demonstrable occlusion pose a management dilemma. The
      authors reviewed their experience to determine the clinical out comes of patients
      with ischemic stroke evaluated within 6 hours of symptom onset in whom negative
      angiograms were obtained. METHODS: A prospective registry was maintained for all
      patients (N = 56) who were considered for intra-arterial thrombolysis. Patients
      without angiographic arterial occlusion were not treated with thrombolytics, and
      data pertaining to clinical characteristics and neuroimaging findings was
      collected. Follow-up data were acquired through clinic visits or telephone
      interviews at 5.5 +/- 5.0 months (mean +/- SD), range 1 to 15 months, after onset
      of stroke. RESULTS: Of the 56 patients, no arterial occlusion was observed in 17
      (30%) patients (mean age 65.8 +/- 13.0 years; 7 were men). The mean (+/- SD)
      baseline National Institute of Health stroke scale score was 10.2 +/- 7.1.
      Symptoms were referable to the anterior or posterior circulation in 76% and 18%
      of the patients, respectively; they could not be localized to either circulation
      in 6%. Follow-up neuroimaging studies demonstrated cerebral infarction in 12 of
      14 patients. Eleven of the 17 had a favorable long-term recovery as assessed by
      the modified Rankin Scale (score 0 or 1). Five other patients had modified Rankin
      Scale scores of 3 (n = 1), 4 (n = 2), or 5 (n = 2). One patient died during the
      follow-up period. With regard to location of ischemic deficits, the highest rate
      of death or dependency was observed in patients with pontine infarction (three of
      four patients). CONCLUSION: Although the outcome following ischemic stroke in
      patients without angiographically documented occlusion appears to be better than
      that reported for patients with angiographically documented occlusion, death or
      disability is observed in at least one third of the patients. There fore, acute
      ischemic stroke in the absence of angiographic occlusion is not entirely a
      "benign" entity and can be particularly devastating when the brainstem is
      involved.

PMID- 15574573
TI  - Cerebral blood flow effects of pain and acupuncture: a preliminary single-photon
      emission computed tomography imaging study.
AB  - BACKGROUND: The purpose of this study was to investigate the cerebral blood flow
      changes associated with the analgesic effect of acupuncture in patients with
      chronic pain. METHODS: Seven patients presenting with a chronic pain syndrome and
      5 healthy controls were included. All single-photon emission computed tomography
      (SPECT) scans were acquired with a uniform protocol. The patient group was
      injected with the radioisotope hexamethyl propyleneamine oxime (HMPAO) while
      experiencing their usual level of pain. A baseline scan was acquired
      approximately 20 minutes after administration of the HMPAO. The patient then
      underwent acupuncture therapy with needles placed in points specifically selected
      to relieve pain. When the pain improved, as determined by a 10-digit score for
      pain assessment, the patient was reinjected with HMPAO and imaged 20 minutes
      later for the acupuncture scan. The reference group also had a baseline and
      acupuncture scan, although the acupuncture itself was performed using a
      standardized set of needle points. RESULTS: The reference group participants were
      found to have significant increases in the thalamic and prefrontal cortex
      activity on the acupuncture scan compared to the baseline. The baseline scans of
      the pain patients showed significant asymmetric uptake in the thalami compared to
      controls. This asymmetry reversed or normalized after the acupuncture therapy.
      Significant correlations were observed between the change of activity in the
      prefrontal cortex and ipsilateral sensorimotor area. CONCLUSION: The results from
      these cases show that HMPAO-SPECT is capable of detecting changes in cerebral
      blood flow associated with pain and that acupuncture analgesia is associated with
      changes in the activity of the frontal lobes, brain stem, and thalami.

PMID- 15574574
TI  - Clinical and ultrasonographic manifestations in major causes of common carotid
      artery occlusion.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis is the main cause of common carotid
      artery occlusion in most reports. This study aimed to identify the major causes
      of common carotid artery occlusion and compare the clinical features and carotid
      duplex ultrasonography findings of patients with common carotid artery occlusion
      attributable to each cause. METHODS: Patients with common carotid artery
      occlusion documented by carotid duplex ultrasonography at the Neurovascular
      Laboratory (National Taiwan University Hospital) from 1988 to 2003 were included.
      Medical records and ultrasonographic findings were reviewed in detail to clarify
      the possible etiology of common carotid artery occlusion. RESULTS: A total of 44
      patients (male, 27 [61%]; female, 17 [39%]; mean age, 58 years) had common
      carotid artery occlusion attributable to a carotid duplex ultrasonography
      identifiable cause. The causes of common carotid artery occlusion included
      atherosclerosis (17 [39%]), Takayasu's arteritis (11 [25%]), postirradiation
      arteriopathy (7 [16%]), cardiac embolism (6 [14%]), syphilis (1), blunt trauma
      (1), and homocystinuria (1). Among the patients with common carotid artery
      occlusion due to the 4 major causes, 27 (66%) had ischemic stroke and 14 (34%)
      had no symptoms or nonlocalizing symptoms. The frequency of symptomatic com mon
      carotid artery occlusion was 83% in those with cardioembolism, 76% in those with
      atherosclerosis, 71% in those with postirradiation arteriopathy, and 36% in those
      with Takayasu's arteritis. Common carotid artery occlusion usually involved the
      carotid bulb and distal common carotid artery in atherosclerosis (88%) and
      postirradiation arteriopathy (100%), but not in Takayasu's arteritis (27%).
      Echogenicity of occluded material was heterogeneous in atherosclerosis and post
      irradiation arteriopathy patients but homogeneous in all Takayasu's arteritis
      patients. The authors postulate that the thrombotic mechanism might differ
      according to etiology. CONCLUSIONS: The causes of common carotid artery occlusion
      are diverse. Atherosclerosis, Takayasu's arteritis, and post-irradiation
      arteriopathy are the most common causes of com mon carotid artery occlusion in
      Taiwan. The clinical features, pathophysiology, and carotid duplex
      ultrasonography findings vary according to the cause of common carotid artery
      occlusion.

PMID- 15574575
TI  - A noninvasive portable acoustic diagnostic system to differentiate ischemic from
      hemorrhagic stroke.
AB  - PURPOSE: To determine if a noninvasive brain acoustic monitor can differentiate
      acoustic responses from "normal patients" and ischemic from hemorrhagic stroke
      patients. METHODS: A laptop-sized passive acoustic monitoring system acquires
      arterial-pressure-generated signals during a 15-second monitoring session from
      sensors placed at the radial artery and on the fore-head. The arterial pulse
      waveform from the head is compared with that of the arterial waveform to generate
      the time-domain signal comparison. Frequency domain signals from each area are
      also compared. The study involved patients with diagnosis of first stroke who
      could be monitored within 12 hours of symptom onset and normal subjects who
      provided informed consent. Individuals with history of brain injury, stroke, or
      other brain disease were excluded. RESULTS: Twelve normal subjects and 6 ischemic
      stroke, 2 transient ischemic attack (TIA), and 3 hemorrhagic stroke patients were
      monitored. Frequency response analysis identified uniform frequency responses in
      normal subjects. The signal in ischemic stroke patients was characterized by a
      divergence of the radial and cranial frequency response between 10 and 50 Hz of
      10 dB or greater. In intracerebral hemorrhage patients, a divergence was seen
      below 10 Hz but not in the band above 10 Hz. TIA patients were monitored after
      symptom resolution and showed a divergence <10 dB in both bands, similar to
      normal subjects. CONCLUSIONS: In a pilot study using a noninvasive monitor, the
      authors detected a potential to differentiate between normal subjects and those
      with cerebral ischemia or hemorrhage.

PMID- 15574576
TI  - Changes of cerebral hemodynamics in hypertensives during physical exercise.
AB  - BACKGROUND AND PURPOSE: Previously, 30 untreated hypertensive patients were
      investigated by transcranial Doppler (TCD) monitoring during physical exercise,
      and changes of hemodynamic parameters were compared with those of age matched
      healthy subjects. After 3-year antihypertensive (AHT) treatment, these
      hypertensives were investigated again. The aim of this study was to compare the
      cerebral hemodynamic changes in the regularly treated and noncompliant
      (untreated) hypertensives during ergometer cycling. METHODS: Nineteen of 30
      previously untreated hypertensive patients could be investigated again using the
      same method as before. Eleven were regularly treated (treated hypertensive [T-HT]
      group), and 8 did not take their AHT medications due to lack of compliance
      (noncompliant hypertensive [NC-HT] group). Blood pressure, heart rate, end-tidal
      CO2 (etCO2; Capnogard capnograph), and bilateral middle cerebral artery mean
      blood flow velocity (MV) were continuously monitored during ergometer cycling
      according to the World Health Organization protocol. Values of 2-minute loading
      were analyzed. RESULTS: Median loading time did not differ significantly between
      the T-HT and NC-HT groups. After 2 minutes of cycling in treated patients, the
      ratio of MV and etCO changes (DeltaMV/DeltaetCO2) showed similar values as before
      therapy (P = .38), whereas in noncompliant patients, a further worsening of the
      ratio of DeltaMV/DeltaetCO2 could be observed (P = .04). CONCLUSION: The decrease
      of arteriolar vasodilation (ie, the ratio of DeltaMV/DeltaetCO2) could be
      demonstrated in the NC-HT group after 3 years. TCD combined with ergometer
      cycling is a useful method for evaluation of cerebral hemodynamic changes after
      AHT therapy.

PMID- 15574577
TI  - Functional and morphological criteria of internal jugular valve insufficiency as
      assessed by ultrasound.
AB  - BACKGROUND AND PURPOSE: Jugular venous valve insufficiency may play a role in
      different neurological diseases. This study describes the methodology to detect
      internal jugular valve insufficiency and establishes functional and morphological
      criteria to discriminate retrograde flow during valve closure from retro grade
      insufficiency flow. METHODS: Valve closure was assessed in 100 valves (50 healthy
      volunteers). The valves were visualized in B-mode. During a pressure-controlled
      Valsalva maneuver, valve closure was monitored by color duplex. The duration and
      the peak velocity of retrograde flow were determined. RESULTS: Backward flow
      during valve closure in competent valves was visually clearly discernible from a
      retrograde flow jet through insufficient valves. Insufficiency was found in 29%
      of valves. The duration of backward flow in competent valves was between 0.22 and
      0.78 seconds (mean = 0.46 +/- 0.14 seconds on Doppler measurements) and in
      insufficient valves between 1.23 and 6.15 seconds (mean = 2.66 +/- 1.28; P <
      .0001). Peak velocity of retrograde flow in competent valves was between 12 and
      65 cm/s (mean = 26.2 +/- 11.1 cm/s) and between 25 and 160 cm/s (mean = 89.5 +/-
      39.3 cm/s; P < .0001) in insufficient valves. On B-mode imaging, the "typical"
      aspect of an immobile, frozen valve was seen only in 5 cases of insufficient
      valves; 21 insufficient valves did not display this aspect. CONCLUSION: The
      duration of retrograde flow clearly discriminates competent and incompetent
      valves. On the basis of our results, we provide cut off values that help
      differentiate between physiological and insufficiency reflux. The differences in
      peak velocity and morphology criteria are helpful but not reliable to predict
      insufficiency of the valve.

PMID- 15574578
TI  - Intracranial area: a validated method for estimating intracranial volume.
AB  - BACKGROUND AND PURPOSE: Controlling for intracranial volume is crucial in
      magnetic resonance studies of changes in brain volumes. However, full
      intracranial volume measurement requires prolonged scanning and analysis, and
      simple, validated methods for intracranial volume estimation are lacking. The
      authors developed and evaluated a method of estimating intracranial volume using
      a single mid-sagittal slice, the intracranial cross-sectional area. METHODS:
      Forty men aged 65-70 had whole skull magnetic resonance scans at 1.9 T, with
      slice thickness of 1.5 mm (no interslice gap). Intracranial cross-sectional area
      was traced in the midline sagittal slice of the 3-view localizer. Intracranial
      volume was measured using every slice. Ten intracranial cross-sectional area
      measurements were tested for interrater reliability. RESULTS: Intracranial cross
      sectional area and intracranial volume correlated highly (r = .88, P < .0001). A
      modified Bland-Altman plot showed good agreement between intracranial cross
      sectional area and intracranial volume. The intraclass correlation (an indicator
      of reliability) for intracranial cross-sectional area was r = .976 (P < .005).
      CONCLUSIONS: The rapid and simple technique of intracranial cross-sectional area
      measurement provides a valid and reliable estimate of intracranial volume.

PMID- 15574579
TI  - Extensive brain stem lesions in thrombotic thrombocytopenic purpura: repeat
      magnetic resonance findings.
AB  - The authors report on an unusual case of extensive brain stem lesions as a
      manifestation of thrombotic thrombocytopenic purpura (TTP). A 28-year-old woman
      developed rapidly progressive neurologic deficits 5 days after a cesarean
      delivery. Her condition had been normal after delivery. Initial magnetic
      resonance imaging (MRI) revealed extensive T2 hyperintense lesions involving the
      entire brain stem; only part of the pons showed hyperintense abnormalities in a
      concomitantly taken diffusion-weighted image. The hematologic evaluations and her
      clinical course revealed the diagnosis of TTP, so plasma exchange and methyl
      prednisolone therapy were initiated. After 10 days of treatment, she developed
      neurologic improvement. A follow-up MRI on the 75th day revealed dramatically
      reduced brain stem lesions with only residual punctate lesions in the pons. Her
      remaining neurologic deficits were dysarthria, limb ataxia, and left hemiparesis.
      As demonstrated in this study, extensive brain stem involvement should be added
      as a possible neuroimaging feature of TTP.

PMID- 15574580
TI  - Pure sensory stroke as an isolated manifestation of the lateral medullary
      infarction.
AB  - Pure sensory stroke is a common manifestation of a thalamic stroke and may occur
      less frequently in the infarction of the brainstem, internal capsule, and
      parietal cortex. The authors report a 47-year-old man who presented with loss of
      pain and temperature sensation in the left face, arm, trunk, and leg and was
      found to have a right lateral medullary infarction on diffusion-weighted magnetic
      resonance imaging. To the authors' knowledge, this is the first case describing
      pure sensory stroke as a single, isolated manifestation of the lateral medullary
      infarction that was detected by diffusion-weighted magnetic resonance imaging.
      This case suggests that with the availability of diffusion-weighted magnetic
      resonance imaging, pure sensory stroke may carry a broader spectrum of the
      anatomical localizations than previously determined and can localize to the
      lateral medulla. Therefore, a possibility of medullary infarction should be
      considered when a patient presents with pure sensory stroke, especially when
      diffusion-weighted magnetic resonance imaging is not immediately available to
      provide radiographic correlation.

PMID- 15574581
TI  - Bilateral basal ganglia and cerebellar lesions in an alcoholic hyperosmolar
      patient.
AB  - Bilateral symmetrical basal ganglia lesions may be caused by hypoxic/ischemic
      injury. However, similar lesions have not been described in the cerebellar
      cortex. To report a case of bilateral basal ganglia and cerebellar lesions in an
      alcoholic patient with hyperglycemia and hypotension. A 47-year-old alcoholic man
      with hypotension of unknown duration and hyperosmolarity had mild weakness of the
      left upper extremity. Neuroimaging revealed abnormality of bilateral symmetric
      globus pallidus and inferior cerebellum. Prolonged hypotension with
      hyperosmolarity may give rise to bilateral basal ganglia and cerebellar lesions.

PMID- 15574582
TI  - Magnetoencephalographic analysis of secondary bilateral synchrony.
AB  - To assess the clinical value of magnetoencephalography (MEG) in investigating the
      origin of secondary bilateral synchrony (SBS) in patients with partial epilepsy.
      MEG and simultaneous electroencephalography (EEG) were recorded with a 204
      channel whole-head MEG system in 2 patients. The equivalent current dipoles
      (ECDs) for epileptic discharges on MEG were calculated according to a single
      dipole model. In patient 1, the ictal EEG showed bursts of bilateral synchronous
      3-Hz spike-and-slow-wave complexes. ECDs obtained from the ictal MEG localized to
      the right medial frontal lobe. On the second patient's MEG recordings, epileptic
      discharges corresponding to prolonged EEG bursts of bilateral synchronous spike
      and-slow-wave complexes were obtained. ECDs calculated from the prolonged bursts
      were clustered in the left medial frontal lobe. MEG detected the sources of SBS
      in the medial frontal lobe. MEG is extremely useful for the identification of the
      source of SBS.

PMID- 15574583
TI  - Diffuse cerebral air embolism treated with hyperbaric oxygen: a case report.
AB  - A 54-year-old woman presented for cardiac evaluation of atypical chest pain.
      Workup included coronary angiography and a left ventriculogram, during which air
      was inadvertently injected, resulting in the development of an acute right
      hemisphere syndrome. Right carotid angiography was immediately performed,
      yielding only a delayed diffuse venous phase without focal vessel cutoffs. Within
      60 minutes, the patient underwent hyperbaric oxygen therapy for the suspected
      cerebral air emboli. After removal from the chamber for technical reasons, she
      had a generalized tonic-clonic seizure, and further hyperbaric oxygen therapy was
      withheld. Initial computed tomography imaging obtained approximately 8 hours
      after symptom onset showed signs of early right hemispheric edema. Subsequent
      magnetic resonance imaging studies were markedly abnormal and suggestive of
      diffuse bilateral but predominantly right-sided parietal lobe edema with mildly
      positive diffusion-weighted imaging. Follow-up magnetic resonance imaging at 6
      months was normal, and the patient's neurological examination returned to normal.

PMID- 15574586
TI  - A role for beta-actin in RNA polymerase III transcription.
AB  - When transcription from the human U6 snRNA gene is reconstituted with recombinant
      factors and purified RNA polymerase III (pol III), pol III must be treated with
      CK2 to be active. We show that highly purified pol III contains associated beta
      actin, and beta-actin localizes to an active U6 promoter in vivo. Pol III
      immunoprecipitated from IMR90 cells treated with a genotoxic agent lacks
      associated beta-actin and is inactive in the reconstituted assay. Transcription
      is regained upon treatment of pol III with CK2 and addition of beta-actin. This
      suggests that beta-actin associated with pol III is essential for basal pol III
      transcription.

PMID- 15574587
TI  - Smurf2 up-regulation activates telomere-dependent senescence.
AB  - Progressive telomere shortening activates replicative senescence, which prevents
      somatic cells from being propagated indefinitely in culture. The limitation of
      proliferative capacity imposed by replicative senescence is thought to contribute
      to both organismal aging and the prevention of tumor development. Here we report
      that up-regulation of Smurf2, an E3 ubiquitin ligase previously implicated in TGF
      beta signaling, is a specific consequence of telomere attrition in human
      fibroblasts and that such up-regulation is sufficient to produce the senescence
      phenotype. Adventitious production of the Smurf2 protein in early passage
      fibroblasts at the same physiological level observed during telomere-mediated
      senescence resulted in proliferative arrest in a viable state, morphological and
      biochemical alterations characteristic of senescence, acquisition of senescence
      specific alterations in gene expression, and reversal of cellular immortalization
      by telomerase. We show that the senescence-inducing actions of Smurf2 occur in
      the absence of detectable DNA damage or stress response, that Smurf2's effects
      require a novel function distinct from its E3 activity, that Smurf2 recruits the
      Rb and p53 pathways for senescence induction, and that while p21 is elevated by
      Smurf2, Smurf2-mediated senescence is independent of p21. Smurf2 is the first
      gene found to be both up-regulated by telomere attrition and sufficient to induce
      senescence.

PMID- 15574588
TI  - The AMP-activated protein kinase AAK-2 links energy levels and insulin-like
      signals to lifespan in C. elegans.
AB  - Although limiting energy availability extends lifespan in many organisms, it is
      not understood how lifespan is coupled to energy levels. We find that the AMP:ATP
      ratio, a measure of energy levels, increases with age in Caenorhabditis elegans
      and can be used to predict life expectancy. The C. elegans AMP-activated protein
      kinase alpha subunit AAK-2 is activated by AMP and functions to extend lifespan.
      In addition, either an environmental stressor that increases the AMP:ATP ratio or
      mutations that lower insulin-like signaling extend lifespan in an aak-2-dependent
      manner. Thus, AAK-2 is a sensor that couples lifespan to information about energy
      levels and insulin-like signals.

PMID- 15574589
TI  - The Drosha-DGCR8 complex in primary microRNA processing.
AB  - RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear
      RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped
      pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to
      generate mature miRNAs. While Dicer (class III) and other simple RNase III
      proteins (class I) have been studied intensively, the class II enzyme Drosha
      remains to be characterized. Here we dissected the action mechanism of human
      Drosha by generating mutants and by characterizing its new interacting partner,
      DGCR8. The basic action mechanism of Drosha was found to be similar to that of
      human Dicer; the RNase III domains A and B form an intramolecular dimer and
      cleave the 3' and 5' strands of the stem, respectively. Human Drosha fractionates
      at approximately 650 kDa, indicating that Drosha functions as a large complex. In
      this complex, Drosha interacts with DGCR8, which contains two double-stranded RNA
      (dsRNA)-binding domains. By RNAi and biochemical reconstitution, we show that
      DGCR8 may be an essential component of the pri-miRNA processing complex, along
      with Drosha. Based on these results, we propose a model for the action mechanism
      of class II RNase III proteins.

PMID- 15574590
TI  - synMuv verite--Myb comes into focus.

PMID- 15574591
TI  - A systems view of mRNP biology.
AB  - Gene expression occurs through a complex mRNA-protein (mRNP) system that
      stretches from transcription to translation. Gene expression processes are
      increasingly studied from global perspectives in order to understand their
      pathways, properties, and behaviors as a system. Here we review these beginnings
      of mRNP systems biology, as they have emerged from recent large-scale
      investigation of mRNP components, interactions, and dynamics. Such work has begun
      to lay the foundation for a broader, integrated view of mRNP organization in gene
      expression.

PMID- 15574592
TI  - Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5
      complex that promotes APOBEC3G degradation.
AB  - HIV-1 Vif (viral infectivity factor) protein overcomes the antiviral activity of
      the DNA deaminase APOBEC3G by targeting it for proteasomal degradation. We report
      here that Vif targets APOBEC3G for degradation by forming an SCF-like E3
      ubiquitin ligase containing Cullin 5 and Elongins B and C (Cul5-EloB-EloC)
      through a novel SOCS (suppressor of cytokine signaling)-box that binds EloC. Vif
      binding to EloC is negatively regulated by serine phosphorylation in the BC-box
      motif of the SOCS-box. Vif ubiquitination is promoted by Cul5 in vitro and in
      vivo, and requires an intact SOCS-box. Thus, autoubiquitination of Vif occurs
      within the assembled Vif-Cul5 complex, analogous to F-box proteins that are
      autoubiquitinated within their SCF (Skp1-Cullin-F-box) complex. These findings
      suggest mechanisms that regulate the assembly and activity of Cul5 E3 complexes
      through phosphorylation or autoubiquitination of the SOCS-box protein, and
      identify interactions between Vif and host cell proteins that may be therapeutic
      targets.

PMID- 15574593
TI  - Selective assembly of HIV-1 Vif-Cul5-ElonginB-ElonginC E3 ubiquitin ligase
      complex through a novel SOCS box and upstream cysteines.
AB  - APOBEC3G, which induces hypermutations in newly synthesized viral DNA, is
      suppressed by HIV-1 Vif, acting through Cul5-ElonginB-ElonginC E3 ubiquitin
      ligase. We have now characterized a novel SOCS box in HIV-1 Vif that mediates its
      interaction with ElonginC. In this SOCS box, alanine replaces the consensus
      cysteine in the previously identified SOCS box. This new motif was necessary but
      insufficient for interaction with Cul5-ElonginB-ElonginC, as two highly conserved
      Cys residues outside the SOCS box were required to interact with Cul5 but not
      ElonginC. Therefore, selective assembly with Cul5 versus Cul2 E3 may require
      protein interfaces besides the SOCS-box-ElonginC interaction.

PMID- 15574594
TI  - Zipper-like interaction between proteins in adjacent daughter cells mediates
      protein localization.
AB  - Protein localization is crucial for cellular morphogenesis and intracellular
      signal transduction cascades. Here we describe an interaction between two
      membrane proteins expressed in different cells of the Bacillus subtilis
      sporangium, the mother cell protein SpoIIIAH and the forespore protein SpoIIQ. We
      used affinity chromatography, coimmunoprecipitation, and the yeast two-hybrid
      system to demonstrate that the extracellular domains of these proteins interact,
      tethering SpoIIIAH to the sporulation septum, and directing its assembly with
      SpoIIQ into helical arcs and foci around the forespore. We also demonstrate that
      this interaction can direct proteins made in the same cell to active division
      sites, as when SpoIIQ is made in the mother cell, it localizes to nascent septa
      in a SpoIIIAH-dependent manner. Both SpoIIIAH and SpoIIQ are necessary for
      activation of the second forespore-specific transcription factor (sigma(G)) after
      engulfment, and we propose that the SpoIIIAH-SpoIIQ complex contributes to a
      morphological checkpoint coupling sigma(G) activation to engulfment. In keeping
      with this hypothesis, SpoIIIAH localization depends on the first step of
      engulfment, septal thinning. The SpoIIQ-SpoIIIAH complex reaches from the mother
      cell cytoplasm to the forespore cytoplasm and is ideally positioned to govern the
      activity of engulfment-dependent transcription factors.

PMID- 15574595
TI  - A role for E2F6 in distinguishing G1/S- and G2/M-specific transcription.
AB  - E2F transcription factors play a critical role in the control of cell cycle
      progression, regulating the expression of genes involved in DNA replication, DNA
      repair, mitosis, and cell fate. This involves both positive-acting and negative
      acting E2F proteins, the latter group including the E2F6 protein, which has been
      shown to function as an Rb-independent repressor of E2F-target gene
      transcription. In an effort to better delineate the context of E2F6 function,
      including the mechanisms of E2F6 functional specificity, we used chromatin
      immunoprecipitation assays to assess when and with what genes E2F6 associates
      during a cell cycle. We find that E2F6 associates specifically with the E2F
      target genes that are activated at G1/S; this interaction occurs during S phase
      of the cell cycle. In sharp contrast, E2F6 does not bind to E2F-regulated genes
      activated at G2/M. In the absence of E2F6, E2F4 can bind to the G1/S-regulated
      promoters and compensate for loss of E2F6 function. Indeed, inhibition of both
      E2F4 and E2F6 activity results in specific derepression of these genes during S
      phase. We conclude that E2F6 functions as a repressor of E2F-dependent
      transcription during S phase and given the specificity for the G1/S-regulated
      genes, we propose that E2F6 functions to distinguish G1/S and G2/M transcription
      during the cell cycle.

PMID- 15574596
TI  - Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107
      and p130.
AB  - The retinoblastoma gene family consists of three genes: RB, p107, and p130. While
      loss of pRB causes retinoblastoma in humans and pituitary gland tumors in mice,
      tumorigenesis in other tissues may be suppressed by p107 and p130. To test this
      hypothesis, we have generated chimeric mice from embryonic stem cells carrying
      compound loss-of-function mutations in the Rb gene family. We found that Rb/p107-
      and Rb/p130-deficient mice were highly cancer prone. We conclude that in a
      variety of tissues tumor development by loss of pRB is suppressed by its homologs
      p107 and p130. The redundancy of the retinoblastoma proteins in vivo is reflected
      by the behavior of Rb-family-defective mouse embryonic fibroblasts in vitro.

PMID- 15574597
TI  - Chromatin remodeling and histone modification in the conversion of
      oligodendrocyte precursors to neural stem cells.
AB  - We showed previously that purified rat oligodendrocyte precursor cells (OPCs) can
      be induced by extracellular signals to convert to multipotent neural stem-like
      cells (NSLCs), which can then generate both neurons and glial cells. Because the
      conversion of precursor cells to stem-like cells is of both intellectual and
      practical interest, it is important to understand its molecular basis. We show
      here that the conversion of OPCs to NSLCs depends on the reactivation of the sox2
      gene, which in turn depends on the recruitment of the tumor suppressor protein
      Brca1 and the chromatin-remodeling protein Brahma (Brm) to an enhancer in the
      sox2 promoter. Moreover, we show that the conversion is associated with the
      modification of Lys 4 and Lys 9 of histone H3 at the same enhancer. Our findings
      suggest that the conversion of OPCs to NSLCs depends on progressive chromatin
      remodeling, mediated in part by Brca1 and Brm.

PMID- 15574598
TI  - Su(var) genes regulate the balance between euchromatin and heterochromatin in
      Drosophila.
AB  - Histone lysine methylation is an epigenetic mark to index chromosomal subdomains.
      In Drosophila, H3-K9 di- and trimethylation is mainly controlled by the
      heterochromatic SU(VAR)3-9 HMTase, a major regulator of position-effect
      variegation (PEV). In contrast, H3-K27 methylation states are independently
      mediated by the Pc-group enzyme E(Z). Isolation of 19 point mutants demonstrates
      that the silencing potential of Su(var)3-9 increases with its associated HMTase
      activity. A hyperactive Su(var)3-9 mutant, pitkin(D), displays extensive H3-K9 di
      and trimethylation within but also outside pericentric heterochromatin. Notably,
      mutations in a novel Su(var) gene, Su(var)3-1, severely restrict Su(var)3-9
      mediated gene silencing. Su(var)3-1 was identified as "antimorphic" mutants of
      the euchromatic H3-S10 kinase JIL-1. JIL-1(Su(var)3-1) mutants maintain kinase
      activity and do not detectably impair repressive histone lysine methylation
      marks. However, analyses with seven different PEV rearrangements demonstrate a
      general role of JIL-1(Su(var)3-1) in controlling heterochromatin compaction and
      expansion. Our data provide evidence for a dynamic balance between
      heterochromatin and euchromatin, and define two distinct mechanisms for Su(var)
      gene function. Whereas the majority of Su(var)s encode inherent components of
      heterochromatin that can establish repressive chromatin structures [intrinsic
      Su(var)s], Su(var)3-1 reflects gain-of-function mutants of a euchromatic
      component that antagonize the expansion of heterochromatic subdomains [acquired
      Su(var)s].

PMID- 15574599
TI  - Characteristics of ice hockey-related injuries treated in US emergency
      departments, 2001-2002.
AB  - OBJECTIVE: Ice hockey, a popular sport in some regions, has potential for injury
      due to the velocities of players, pucks, and sticks. Previous studies conducted
      worldwide have shown that the rate of injury increases as the size and the speed
      of players increase, as well as when checking is allowed. However, national data
      about the annual number and types of injuries among ice hockey players are
      lacking. Data from previous studies were collected from regional tournaments,
      collegiate teams, local emergency departments (EDs), and different countries. The
      purpose of this article is to examine ice hockey injuries using a national US
      database to determine the age distribution of total injuries, injury types, and
      body regions injured, with a particular focus on ice hockey players <18 years
      old. METHODS: Data regarding ice hockey-related injuries treated in US EDs
      between January 1, 2001, and December 31, 2002, were extracted from the National
      Electronic Injury Surveillance System (NEISS). Data considered included age,
      gender, race, injury diagnosis, and body region injured. Ice hockey-related
      injury cases were identified using the consumer product code for ice hockey and
      the narrative description of the incident in NEISS. RESULTS: An estimated 32,750
      individuals with ice hockey-related injuries were treated in US EDs in 2001-2002,
      including >18,000 youths <18 years old. The number of injuries peak through
      adolescence (ages 12-17; 47% of all injuries). Males experienced 90% of all
      injuries. A very small percentage of individuals were hospitalized after injury
      (1.2% of individuals <18 years old; 0.5% of individuals > or =18 years old). The
      incidence of head injuries increased as age decreased, although the trend was not
      statistically significant. The upper extremity (44%) accounted for the highest
      total percentages of body regions injured for youths <18 years old, and trunk
      (14%) and facial injuries (10%) represented the smallest total percentages.
      Players > or =18 years old had significantly more lacerations than younger
      players (38% of injuries for 18- to 24-year-olds; 25% for 25- to 34-year-olds;
      50% for 35- to 44-year-olds compared with 19% for 6- to 11-year-olds and 14% for
      12- to 17-year-olds). CONCLUSIONS: Adolescents had the greatest number of ice
      hockey-related injuries treated in NEISS hospital EDs in 2001-2002; thus, ongoing
      efforts to develop injury prevention strategies should focus on this age group.
      Players < or =17 years old had a lower percentage of lacerations compared with
      all older players and a higher percentage of upper extremity injuries. The
      percentage of individuals hospitalized after injury was very low, yet youths <18
      years old had twice the percentage of hospitalization after injury compared with
      individuals > or =18 years old. Males experienced the vast majority of all ice
      hockey-related injuries, with females representing a higher percentage of
      injuries among youths than among adults. Children and adults alike can reap the
      physical fitness and social benefits from ice hockey, when they are able to avoid
      predictable and preventable injuries.

PMID- 15574600
TI  - Epidemiologic features of Kawasaki disease in Taiwan, 1996-2002.
AB  - OBJECTIVE: Kawasaki disease (KD) is the most common acquired heart disease in
      children worldwide. The incidence of KD varies among different countries, with
      Asian countries supposedly having higher incidences than Western countries.
      However, the incidence of KD in Taiwan has not been well investigated. METHODS:
      Since the implementation of Taiwan's National Health Insurance (NHI) in 1995, NHI
      has covered health care for >96% its population. Using the NHI database from 1996
      to 2002, we investigated epidemiologic features of KD (International
      Classification of Diseases, Ninth Revision, code 446.1), the rate of coronary
      artery aneurysm formation (International Classification of Diseases, Ninth
      Revision, code 414.11), and the change in incidence during the recent 7 years. We
      also compared the annual incidences in Taiwan with those reported by other
      countries. RESULTS: During the 7-year study period, KD occurred most frequently
      in the summer and least frequently in winter. It is interesting that the highest
      peak occurred in the summer of 1998 at the same time that Taiwan's enterovirus 71
      epidemic was occurring. Ninety-one percent of KD cases occurred in children who
      were <5 years old, and the male-to-female ratio was 1.70:1. Recurrence of KD was
      found in 1.3% (94 of 7305) of these children, and coronary artery aneurysm was
      found in 7.3% (536 of 7305). The annual incidence per 100,000 children was 146 in
      children <1 year old, 98 in 1-year-old children, 51 in 2-year-old children, 28 in
      3-year-old children, 19 in 4-year-old children, and 5.3 in 5- to 9-year-old
      children; the incidence of KD decreased with increased age. The overall incidence
      was 66 cases per 100,000 children <5 years old from 1996 to 2002 with the annual
      incidence not differing significantly during the 7-year study period.
      CONCLUSIONS: KD in Taiwan occurs more frequently in boys and in the summer
      months. During the 7-year study period, the annual KD incidence in Taiwan of
      66/100000 in children <5 years old was the second highest in the world after
      Japan.

PMID- 15574601
TI  - The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in
      defining and managing congenital hypothyroidism.
AB  - BACKGROUND: Thyroid imaging with isotopic iodide (123I) or technetium Tc 99m
      pertechnetate has been available for decades but is not routinely used in newborn
      infants diagnosed with congenital hypothyroidism (CH). Among clinicians who
      believe that presence, absence, or abnormal location of a thyroid does not alter
      management of CH, imaging is not advocated for anatomic diagnosis of CH.
      OBJECTIVE: To define the role of thyroid scintigraphy in diagnosing and managing
      newborn CH. METHODS: Retrospective review of 249 confirmed cases of CH seen at a
      large, group-model managed care organization during the 24-year period extending
      from September 1978 through December 2002. Neonatal thyroid scintigraphy was
      performed in 210 cases (86%): 123I was used in 143 cases (68%), and technetium Tc
      99m pertechnetate was used in 67 cases (32%). To perform scintigraphy with 123I,
      30 to 50 microCi ([1.11-1.85] x 10(6) Bq) of 123I was administered orally; an
      uptake image was taken in 3 to 6 hours; and, if necessary, another image was
      taken in 24 hours. For technetium, 0.5 to 1 mCi ([1.85-3.7] x 10(7) Bq) of
      technetium Tc 99m pertechnetate was administered intravenously with imaging 20
      minutes later. Thyroid dysplasia was defined as an absent or ectopic gland
      requiring lifetime therapy and eutopic thyroid as a normal-appearing thyroid
      gland in the proper location but possibly malfunctioning and requiring therapy.
      RESULTS: Of the 210 infants with CH receiving scintigraphy, 90 (43%) had eutopic
      (normal-appearing) thyroid diagnosed, and 120 (57%) had ectopic or absent gland
      (25% ectopic, 32% absent) diagnosed. Of these 210 infants, ethnicity was known in
      198; of these, 76 (38%) were Latino/Hispanic, and 122 (62%) of the infants were
      non-Latino/non-Hispanic. Prevalence of CH differed between ethnic groups in our
      population of >700,000 newborn infants; total prevalence of CH was 1 per 3139.
      Prevalence of CH in Latino/Hispanic infants was highest at 1 per 1750 infants
      (1:1357 females, 1:2463 males). Prevalence of CH in non-Latino/non-Hispanic
      infants was 1 per 4648 infants (1:3500 females, 1:6914 males). Given that the
      total Kaiser Permanente infant population was approximately 19% Latino/Hispanic,
      the percentage of Latino/Hispanic infants with CH was significantly higher than
      expected. Dysplastic thyroid was more common in Latino/Hispanic females (69%)
      than in non-Latino/non-Hispanic females (52%). The female-to-male ratio of
      patients with CH was 1.9:1. Among the 210 infants with CH, normal thyroid was
      diagnosed more by 123I scintigraphy (49% of cases) than by scintigraphy using
      technetium Tc 99m pertechnetate (31% of cases). Use of technetium Tc 99m
      pertechnetate could have diagnosed dysplastic thyroid in some cases that would be
      considered eutopic had 123I been used. Eight familial cases of CH were
      identified. COMMENTS: CH, a heterogeneous disorder with prevalence influenced by
      familial, ethnic, and gender factors, is more common in Latino/Hispanic females.
      When present, a eutopic thyroid is more likely to be detected by 123I
      scintigraphy; this method is therefore preferred over scintigraphy using
      technetium Tc 99m pertechnetate for optimal management of CH. Parents can then be
      counseled on either the certainty of lifetime therapy (for dysplastic thyroid) or
      the possibility of later discontinuing therapy (for eutopic thyroid, because CH
      may be transient in these children). If the dysplastic thyroid gland is absent or
      ectopic (usually a small sublingual gland), parents can be told that the infant
      will need lifetime thyroid therapy. If the thyroid gland is present in the normal
      position (eutopic) and the condition is transient (as shown by controlled
      withdrawal of thyroid in older children), lifelong treatment may not be needed.
      Parents rightly expect this maximal clinical and laboratory information in the
      immediate newborn period. Some clinicians hesitate to recommend neonatal
      scintigraphy for children with CH because of concern about delaying L-thyroxine
      therapy, concern about radiation exposure, or both. We believe that neither
      concern is warranted. 123I thyroid imaging has been used for many decades without
      evidence of risk for thyroid cancer. Treatment need not be delayed until
      scintigraphy is done. We did not use ultrasonography for thyroid imaging because
      this technique was not available in the early years of our study and may still
      not have sufficient sensitivity. Sources of discrepancy in our study could
      include scintigraphy interpreter bias due to lack of objective standards. We
      cannot estimate the true prevalence of transient CH because not all physicians
      give children with CH a trial off therapy at 2 to 3 years old, even if a eutopic
      thyroid is shown by 123I scintigraphy. Because therapy with L-thyroxine is simple
      and inexpensive and the outcome of untreated CH can be devastating, some parents
      and physicians are reluctant to discontinue treatment in children with CH, even
      when scans show a eutopic thyroid. Additionally, the clinical information
      contained in our database was not detailed enough to enable us to discover all
      cases of CH in which thyroxine therapy was discontinued. Because the study began
      in 1978 (>25 years ago), some patients were unavailable for long-term follow-up.
      In addition to allowing a more rational clinical approach to CH, 123I thyroid
      scintigraphy may help define underlying genetic factors and mechanisms of thyroid
      development and differentiation. This study's findings, that prevalence of CH and
      of thyroid dysplasia differed between genders and among racial/ethnic groups,
      seem to support a genetic basis for CH. Our results confirm previously published
      reports from the State of California Department of Health Services, Genetic
      Disease Branch and other studies describing multiple genetic abnormalities
      associated with CH. CONCLUSIONS: Despite data limitations, we believe that
      neonatal diagnosis of CH represents perhaps the greatest success of newborn
      screening programs. Initial laboratory diagnosis is simple and sufficiently
      accurate; treatment is simple, inexpensive, and effective. Severe mental
      retardation and growth failure can be prevented. Considering today's rapid
      advances in understanding the basic mechanisms of thyroid embryogenesis and gene
      abnormalities, thyroid scintigraphy may provide insight into clinical and genetic
      correlates in CH.

PMID- 15574602
TI  - Unsafe and violent behavior in commercials aired during televised major sporting
      events.
AB  - OBJECTIVE: Injuries are the leading cause of death in children, and media
      exposure seems to increase children's risk-taking behavior. Televised sports are
      commonly viewed by children. The objective of this study was to determine the
      proportion of commercials that depict violence or other unsafe behavior during
      major televised sporting events that are aired before 9:00 pm. METHODS: We
      obtained a list of the 50 sports programs that were most highly rated by Nielsen
      Media Research and that were televised between September 1, 2001, and September
      1, 2002. These 50 programs included Winter Olympics events (n = 15), National
      Football League (NFL) regular season games (n = 14), NFL playoff games (n = 10),
      Major League Baseball World Series and playoff games (n = 7), the NFL Super Bowl
      (n = 1), the National Basketball Association Western Conference Final Game (n =
      1), the College Football Rose Bowl (n = 1), and the National Collegiate Athletic
      Association Basketball Championship game (n = 1). Two other events were reviewed
      as well: the final round of the Masters Golf Championship, because it was the
      only sporting event rated in the top 50 of the previous year that was not
      represented by a similar sporting event in the study year, and the Daytona 500
      National Association for Stock Car Auto Racing race, because it was the only
      event rated among the top 75 of the study year that was not represented by a
      similar event (ie, there were no other golfing or auto racing events reviewed).
      These events were included because different sporting events may attract
      different viewers and different advertisements; thus, their inclusion provides a
      more comprehensive evaluation of the topic. For sporting events with >3 programs
      in the top 50 (NFL regular season games, NFL playoff games, Winter Olympic
      events, and Major League Baseball World Series), representative samples of events
      were assessed. Surrogate events were analyzed for programs that were aired after
      9:00 PM (Eastern Time) to control for the reduced likelihood of viewing by
      children after 9:00 PM. For example, afternoon telecasts of the National
      Collegiate Athletic Association Regional Final and National Semifinal games were
      assessed in place of the Championship game, which started after 9:00 PM. Weekend
      afternoon telecasts of the Winter Olympics (3 successive weekends) were assessed
      as surrogates for all Olympics telecasts. For the World Series, the Super Bowl,
      and the National Basketball Association Conference Championship games, which
      began before 9:00 PM but ended after that time, we evaluated only commercials
      that aired before 9:00 PM. All commercials that were aired during these programs
      were reviewed at standard speed for unsafe behavior or violence. Commercials that
      were aired during pregame, postgame, or halftime periods were not assessed.
      Commercials were categorized according to the product being advertised. Unsafe
      behavior was simply defined as any action that could have harmful consequences or
      that contravened the injury prevention recommendations of national organizations.
      Violence was defined as any intentional physical contact by an aggressor that had
      the potential to inflict injury or harm or the legitimate threat of such action.
      All commercials were reviewed by at least 2 investigators; when the 2 could not
      agree on the findings, a third investigator was used to resolve differences. The
      percentage of commercials and of commercial breaks that portrayed violent or
      unsafe behavior was determined for each category of event and advertised product.
      A commercial break was defined as a series of commercials shown during a single
      break from the sporting event. chi2 analysis was used for all analyses, and
      relative risks with 95% confidence intervals were determined. The proportion of
      commercials that depicted unsafe behavior and/or violence during each sporting
      event was compared with the proportion of such commercials that were observed
      during the Masters Golf Tournament (which had the lowest proportion of
      commercials depicting such behavior). The proportion of commercials that
      contained violent/unsafe behavior for each advertised product was compared with
      the proportion of such commercials that advertised food or nonalcoholic
      beverages. Food and nonalcoholic beverage commercials were selected as the
      reference because they are a well-defined, common category of commercial.
      RESULTS: Of the 1185 commercials assessed, 14% (n = 165) displayed unsafe
      behavior and 6% (n = 66) depicted violence. Of the 322 commercial breaks, 158
      (49%) contained at least 1 commercial showing unsafe behavior or violence. Sixty
      three commercials required review by a third investigator to adjudicate violence
      or unsafe behavior; 20 of 52 were ultimately judged to portray unsafe behavior,
      and 4 of 11 were ultimately judged to portray violence. Sporting events differed
      in the proportion of commercials that showed violence or unsafe behavior. The
      Super Bowl had the highest proportion of such commercials, and the Masters Golf
      Tournament had the least (relative risk: 4.3; 95% confidence interval: 1.4-12.5).
      The Masters Golf Tournament was noteworthy for the complete absence of violent
      commercials. Only 18% of reviewed commercials advertised movies or television
      programs, yet these commercials accounted for 86% of all violent commercials.
      Forty-eight percent of commercials that contained violence were for movies, and
      an additional 38% were for television programs. Nearly two thirds of all
      commercials for movies contained violence, whereas 15% of all commercials for
      television programs contained violence, a rate that increased to 22% when
      commercials for other sporting events were excluded. Several categories of
      commercials portrayed unsafe behaviors; commercials for automobiles accounted for
      the most. In 8 different categories, 10% or more of the commercials depicted
      unsafe behavior, and 7 were significantly more likely to depict such behavior
      than a food or beverage commercial. CONCLUSIONS: Children who watch televised
      sports view a significant amount of violent and unsafe behavior. In accordance
      with American Academy of Pediatrics recommendations for television viewing,
      parents should both limit and directly supervise children's viewing of these
      events. Our findings suggest that parents should remain present during
      commercials or should consider implementing commercial-skipping technology. In
      addition, efforts should be made to regulate the content of commercials that
      promote television programs and movies on the basis of the hour at which the
      sporting event is aired. Moreover, the sports, movie, and television industries
      should be encouraged to adopt models of advertising that limit or eliminate such
      content. These efforts could help to ensure that the viewing of televised
      sporting events is a safe and positive experience for children.

PMID- 15574603
TI  - Indicators of acute bacterial meningitis in children at a rural Kenyan district
      hospital.
AB  - OBJECTIVE: Acute bacterial meningitis remains an important cause of death and
      neurologic sequelae in African children. The clinical features of meningitis are
      often nonspecific and in this setting may overlap with those of malaria. Early
      diagnosis and appropriate antibiotic treatment are perhaps the most important
      steps in management, but published data suggest that fewer than half of the cases
      of childhood meningitis are identified at first assessment in hospitals in this
      region. The objective of this study was to identify clinical indicators of acute
      bacterial meningitis by examining components of the World Health Organization
      Integrated Management of Childhood Illness (IMCI) referral criteria for
      meningitis (lethargy, unconsciousness, inability to feed, stiff neck, or
      seizures) and other symptoms and signs. METHODS: Kilifi District Hospital,
      serving approximately 200,000 people in a rural, malaria-endemic area of the
      Kenyan coast, was studied. A Kenya Medical Research Institute research center is
      located at the hospital. All pediatric admissions aged > or =60 days between June
      2001 and July 2002 were eligible. RESULTS: A total of 91 (2.0%) of 4582
      admissions had meningitis, including 77 (4.0%) of 1929 of those who met the IMCI
      referral criteria for meningitis at admission (sensitivity: 85%; specificity:
      59%). Independent indicators of the presence of meningitis were a bulging
      fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures, and
      seizures outside the febrile convulsions age range. One or more of these
      indicators was present in 895 (19%) of admissions, 72 (8.0%) of whom had
      meningitis (sensitivity: 79%; specificity: 80%). Independent indicators of the
      absence of meningitis were the absence of a history of fever, a history of
      diarrhea, and a positive malaria slide. The area under the receiver operating
      characteristic curve for a set of simple screening rules based on the positive
      indicators identified was 0.88 (95% confidence interval: 0.85-0.92). CONCLUSIONS:
      The presence of > or =1 of a bulging fontanel, neck stiffness, cyanosis, impaired
      consciousness, partial seizures, and seizures outside the febrile convulsions age
      range is a clear indication for lumbar puncture and/or presumptive treatment.
      However, careful observation and reassessment may be the only practical way to
      identify one fifth of meningitis cases in this setting.

PMID- 15574604
TI  - Topical 4% amethocaine gel reduces the pain of subcutaneous measles-mumps-rubella
      vaccination.
AB  - OBJECTIVES: Ametop gel (4% amethocaine) is a relatively new topical anesthetic
      that produces anesthesia within 30 to 45 minutes and therefore may be appropriate
      for use in busy outpatient settings. The objective of this study was to assess
      the efficacy and safety of 4% amethocaine in reducing the pain of subcutaneous
      measles-mumps-rubella vaccination in 1-year-old infants. METHODS: A double-blind,
      randomized, placebo-controlled trial was conducted in pediatric outpatient
      clinics. RESULTS: A total of 120 infants participated in the study; 60 were
      followed up for assessment of antibody titers after 1 month. Either 1 g of
      amethocaine or placebo was applied for 30 minutes before vaccination. The
      Modified Behavioral Pain Scale was used to assess pain; the mean (standard
      deviation) pain scores for the amethocaine group (n = 61) was 1.5 (1.6) versus
      2.3 (2.2) for the placebo group (n = 59). The rate of vaccination success (88%
      and 87%) was not different between treatment groups. CONCLUSIONS: 4% Amethocaine
      significantly reduces the pain of measles-mumps-rubella vaccination in infants
      when compared with placebo and does not seem to interfere with subsequent
      development of protective antibody levels. Because of its relatively short
      application time (30 minutes), 4% amethocaine may be suitable for busy clinics
      and emergency departments.

PMID- 15574605
TI  - Dental caries of refugee children compared with US children.
AB  - OBJECTIVE: Dental care is a major unmet health need of refugee children. Many
      refugee children have never received oral health care or been exposed to common
      preventive oral health measures, such as a toothbrush, fluoridated toothpaste, or
      fluoridated water. Oral health problems among refugee children are most likely to
      be detected first by pediatricians and family practitioners. Given the increased
      influx of refugees into the United States, particularly children, it is important
      for the pediatric community to be aware of potential oral health problems among
      refugee children and be able to make referrals for treatment and recommendations
      for the prevention of future oral diseases. The purpose of this study was to
      describe the prevalence of caries experience and untreated decay among newly
      arrived refugee children stratified by their region of origin and compared with
      US children. METHODS: Oral health assessments were conducted within 1 month of
      arrival to the United States as part of the Refugee Health Assessment Program of
      the Massachusetts Department of Public Health. The outcome variables include
      caries experience and untreated decay. Caries experience is determined by the
      presence of an untreated caries lesion, a restoration, or a permanent molar tooth
      that is missing because it has been extracted as a result of dental caries.
      Untreated caries is detected when 0.5 mm of tooth structure is lost and there is
      brown coloration of the walls of the cavity. Comparisons of the refugee children
      with US children in Third National Health and Nutrition Examination Survey data
      were made using chi2 test of independence and multiple logistic regression.
      RESULTS: Oral health screenings were performed on 224 newly arrived refugees who
      ranged in age from 6 months to 18 years and had a mean age of 10.6 years (SD:
      4.82; median: 10.7 years). African refugees represented 53.6%, with the majority
      from Somalia, Liberia, and Sudan. Eastern European refugees composed 26.8% of the
      study sample. The remaining 19.6% come from a number of countries, such as
      Afghanistan, Pakistan, and the Middle East. Refugee children had 51.3% caries
      experience and 48.7% with untreated decay. Caries experience in refugees varied
      by region of origin, with 38% from Africa exhibiting a history of caries compared
      with 79.7% of Eastern Europeans. The highest proportion of children with no
      obvious dental problems was from Africa (40.5%) compared with 16.9% from Eastern
      Europe. US children had caries experience similar to that of refugees (49.3%) but
      significantly lower risk of untreated decay (22.8%). Comparisons between refugee
      children and US children found significant differences for treatment urgency,
      untreated caries, extent of dental caries, and presence of oral pain. White
      refugee children, primarily from Eastern Europe, were 2.8 times as likely to have
      caries experience compared with white US children, with 9.4 times the risk of
      untreated decay compared with white US children. In contrast, African refugee
      children were only half as likely to have caries experience compared with white
      US children (95% confidence interval: 0.3-0.7) and African American children (95%
      confidence interval: 0.3-0.7). However, African refugee children were similar to
      African American children in risk of untreated decay (odds ratio: 0.94).
      CONCLUSION: African refugee children had significantly lower dental caries
      experience as well as fewer untreated caries as compared with similarly aged
      Eastern European refugee children. They were also less likely to have ever been
      to a dentist. Possible reasons for these findings may include differences in
      exposure to natural fluoride in the drinking water, dietary differences, access
      to professional care, and cultural beliefs and practices. The prevalence of
      caries experience and untreated caries differed significantly between refugee
      children and US children. These differences varied significantly by race. When
      refugee children were compared with US children, the African refugee children had
      only half the caries experience of either white or African American children.
      However, African refugee children had similar likelihood of having untreated
      caries as compared with African American children, despite that very few African
      children had previous access to professional dental care. These findings are
      consistent with previous studies on health disparities in the United States.
      White refugee children, primarily from Eastern Europe, were also 3 times as
      likely to have caries experience compared with either white or African American
      children and were 9.4 times as likely to have untreated caries as white US
      children. Refugee children are more likely to establish primary medical care
      before seeking dental treatment. With the limited access to dental care among
      refugees, pediatricians should be particularly alert to the risk of oral diseases
      among refugee children.

PMID- 15574606
TI  - On-time immunization rates among children who enter Chicago public schools.
AB  - OBJECTIVE: A primary objective of the Healthy People 2010 initiatives is to
      increase on-time immunization rates during the first 2 years of life and to
      decrease racial disparities in coverage. The objective of this study was to
      determine on-time immunization coverage rates among infants and toddlers
      stratified by race/ethnicity in a large metropolitan center. METHODS: A
      retrospective cohort study that was based on immunization records in the Chicago
      Public Schools computerized database was conducted using all 67376 children who
      completed kindergarten in 2001 and 2002. RESULTS: On-time immunization rates in
      Chicago public school children are low (31% at 7 months, 32% at 19 months, 59% at
      36 months). At 19 months of age and thereafter, Hispanic children had the highest
      rate of on-time immunization coverage. Among children <48 months old, black
      children had the lowest rates of up-to-date immunization status. At 48 months of
      age, the up-to-date rate for black children improved to a rate similar to white
      children (58%) and by school entry surpassed the up-to-date rate for white
      children (71%). Compared with the recommended 2, 4, 6, and 15 to 18 months
      schedule, black children received 4 doses of diphtheria/tetanus/acellular
      pertussis at a mean age of 10.0, 14.6, 20.4, and 34.5 months of age. In contrast,
      Hispanic children received the same doses at a mean of 4.5, 7.4, 11.0, and 25.1
      month of age. In addition, approximately 25% of black children received the
      majority of their vaccinations >12 months later than the recommended time
      intervals. CONCLUSIONS: Striking immunization delay still exists during the
      infant and toddler years. Targeted efforts are needed to increase on-time
      immunization rates and to decrease racial disparity in immunization coverage.

PMID- 15574607
TI  - Clostridium septicum myonecrosis in congenital neutropenia.
AB  - Severe congenital neutropenia (SCN) and Clostridium septicum myonecrosis is an
      uncommon and life-threatening association requiring urgent combined aggressive
      medical and surgical management. We report 2 cases of SCN (1 with known
      Kostmann's syndrome and 1 not known at presentation to have a congenital
      neutropenic disorder but subsequently received a diagnosis of cyclic neutropenia)
      who presented with spontaneous C septicum myonecrosis. The cases highlight the
      importance of response to recombinant human granulocyte colony-stimulating factor
      in obtaining a satisfactory outcome for these patients. Early, empirical use of
      recombinant human granulocyte colony-stimulating factor in patients who are
      suspected of having a congenital neutropenia and who present with life
      threatening sepsis is recommended.

PMID- 15574608
TI  - Role of pediatricians in advocating life support training courses for parents and
      the public.
AB  - Available literature suggests a need for both initial cardiopulmonary
      resuscitation training and refresher courses. The establishment of a pediatric
      chain of survival for victims of cardiopulmonary arrest is the focus of this
      technical report and is advocated in the accompanying policy statement. Immediate
      bystander cardiopulmonary resuscitation for victims of cardiac arrest improves
      survival for out-of-hospital cardiac arrest. Pediatricians will improve the
      chance of survival of children and adults who experience cardiac arrest by
      advocating for basic life support training and participating in basic life
      support courses as participants and teachers.

PMID- 15574609
TI  - Gaps in the evidence for well-child care: a challenge to our profession.
AB  - BACKGROUND: Up to one third of visits to pediatricians involve health supervision
      (well-child care), and recommendations for office-based preventive interventions
      have dramatically expanded. We reviewed the evidence for the effectiveness of
      these interventions. METHODS: The well-child care recommendations of 7 major
      North American organizations were tabulated. Three types of health supervision
      interventions were recommended, ie, behavioral counseling, screening, and
      prophylaxis. For recommendations common to at least 2 of the 7 organizations,
      evidence of effectiveness was sought from systematic reviews and clinical trials.
      Immunizations were not considered for this review, because they have been
      reviewed elsewhere. RESULTS: Forty-two preventive interventions were recommended
      by > or =2 of the organizations. Limited clinical trials show that counseling can
      change some health risk behaviors; repeated intensive counseling is most likely
      to be effective. Harmful effects were shown for a few behavioral counseling
      interventions. Trials have been conducted for only 2 of the recommended screening
      interventions; therefore, rigorous evidence supporting screening is very limited.
      Trials support the use of folate to prevent neural tube defects, trials of iron
      supplementation do not address developmental outcomes, and trials were not found
      for the other recommended prophylactic interventions. CONCLUSIONS: Limited direct
      evidence was found to support the recommended interventions. Because a large
      number of interventions are routinely recommended and often mandated and because
      the implementation of any recommendation may cause harm (including the
      displacement of other beneficial activities), these recommendations should be
      based on the strongest possible evidence. When recommendations are made,
      supporting evidence should be clearly stated.

PMID- 15574610
TI  - Prevalence and correlates of high-quality basic pediatric preventive care.
AB  - BACKGROUND: The list of recommended pediatric preventive services has grown
      considerably in the past decade, and clinician variability, clinician
      distribution, and other correlates of provision of these basic preventive
      services (BPS) are not known. OBJECTIVE: To describe the proportion of high
      quality basic pediatric preventive services, exclusive of immunizations, reported
      by parents and to identify sociodemographic and health system predictors and
      health service correlates of provision of these services. STUDY DESIGN: The study
      used cross-sectional data on 2041 children, 4 to 35 months of age, in the 2000
      National Survey of Early Childhood Health. OUTCOME MEASURES: The BPS measure
      assesses the receipt of (1) developmental assessment, (2) injury prevention
      counseling, (3) screening for parental smoking, (4) guidance on reading to the
      child, and (5) guidance on 14 other topics (assessed as a composite score). The
      BPS scale categorizes the receipt of services as excellent, good, fair, or poor.
      RESULTS: Most children received excellent (34.9%) or good (31.5%) care, but many
      received fair (24.9%) or poor (8.7%) care. Sociodemographic and health care
      factors such as race/ethnicity, insurance, and practice setting were not
      associated with BPS levels. Higher BPS scores were associated with parental
      reports of longer well-child visits, more counseling regarding family and
      community risk factors, lower rates of delayed or missed care, and greater
      satisfaction. CONCLUSIONS: Two thirds of children receive good or excellent basic
      preventive care, as determined with this composite, and no disparities according
      to race/ethnicity, income, or health insurance status of families (which are
      often found to be associated with health care access) were found. This equitable
      distribution of high-quality care suggests a high level of clinician
      professionalism. Duration of visits may be a key factor to improve quality of
      care. Because of its association with other services, processes, and outcomes of
      care, the BPS scale may serve as a useful construct for monitoring quality and
      stimulating efforts to improve national pediatric preventive care.

PMID- 15574611
TI  - Recognition and management of pediatric fractures by pediatric residents.
AB  - BACKGROUND: Competence in basic orthopedic assessment and interpretation of
      radiographs is important for pediatricians because appropriate initial management
      of fractures can expedite therapy and minimize morbidity. However, requirements
      for training in orthopedics and radiology are poorly defined in pediatric
      residency programs. OBJECTIVE: To assess the ability of pediatric residents to
      recognize and to manage appropriately pediatric fractures. METHODS: This study
      involved administration of a case-based questionnaire with radiographs to
      volunteer categorical pediatric residents in 3 geographically diverse training
      programs. The diagnosis and management of 8 orthopedic complaints were evaluated.
      Responses were scored according to the number of features identified accurately,
      including the presence or absence of a fracture. Residents who were able to
      identify a fracture were assessed with respect to their ability to classify the
      fracture and to provide initial management. The study was pretested with a group
      of pediatric emergency medicine attending physicians, to establish the
      suitability of the cases. RESULTS: Among the 3 residency sites, 102 of 190
      eligible pediatric residents (53.7%) participated, yielding 95 completed
      questionnaires. The mean number of cases in which a resident correctly answered
      the question, "Is a fracture present?" and correctly identified the fractured
      bone (if a fracture was present) was 6.5 +/- 1.2 of 8 cases (81.6%; 95%
      confidence interval: 78.5-84.7%). The diagnostic accuracy of Salter-Harris
      classification in cases in which such fractures were present was 40.9%. The mean
      score of correctly identified features for the resident group was 38.5 +/- 9.4,
      of a possible 64 points (proportion correct: 60.1%; 95% confidence interval: 57.2
      63%). There was a small but significant difference in mean correct responses
      between first-year residents (proportion correct: 55.4%; 95% confidence interval:
      50.8- 60.3%) and third-year residents (proportion correct: 65.1%; 95% confidence
      interval: 60.7-69.5%). There was no association between the proportion of correct
      responses and whether or not residents had taken radiology or orthopedics
      elective courses in medical school. Overall, 43% of cases were both identified
      and managed correctly by the pediatric residents. CONCLUSIONS: For residents from
      the participating training programs, skills in recognizing and managing pediatric
      fractures were suboptimal. Additional review of training requirements is
      necessary to identify more clearly areas of improvement for current curricula.

PMID- 15574612
TI  - Trends in risk factors for cardiovascular disease among children and adolescents
      in the United States.
AB  - BACKGROUND: The increasing prevalence of obesity among children and adolescents
      in recent decades might have affected trends in obesity-associated risk factors
      for cardiovascular disease. PARTICIPANTS AND METHODS: We used data for 12,665
      children and adolescents, 2 to 17 years of age, from the Third National Health
      and Nutrition Examination Survey (1988-1994) and for 3611 children and
      adolescents from National Health and Nutrition Examination Survey 1999-2000.
      RESULTS: For participants 2 to 17 years of age, waist circumference increased 1.6
      cm among male subjects and 2.4 cm among female subjects. Mean systolic blood
      pressure increased by 2.2 mm Hg among children and adolescents 8 to 17 years of
      age. There were significant decreases in concentrations of triglycerides (8.8
      mg/dL) and glucose (2.5 mg/dL) among children and adolescents 12 to 17 years of
      age. Mean concentrations of total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, and glycosylated hemoglobin
      were relatively unchanged. Some changes in means of risk factors varied according
      to age. CONCLUSIONS: The temporal trends for risk factors among children and
      adolescents during the 1990s exhibited different patterns. The effects of the
      increasing prevalence of obesity on the cardiovascular health of children and
      adolescents remain unclear.

PMID- 15574613
TI  - Evaluation of a staff-only hospitalist system in a tertiary care, academic
      children's hospital.
AB  - OBJECTIVE: The staff/housestaff hospitalist system has been evaluated in 2
      pediatric centers in the United States. In Canada, fewer residents and duty hour
      restrictions led to the development of a staff-only hospitalist system. The
      objective of this study was to compare the staff-only pediatric hospitalist
      system and the staff/housestaff hospitalist system with respect to traditional
      outcome measures. DESIGN: This cohort study (staff-only hospitalist system versus
      staff/housestaff system) used electronic health records data (July 1, 1996, to
      June 30, 1997) for all admissions (n = 3807) to the general pediatric inpatient
      unit of an urban, tertiary care, pediatric, teaching hospital in Toronto, Canada.
      Outcome measures included length of hospital stay, subspecialty consultations,
      readmission to the hospital, and death during the hospital stay. RESULTS: The
      median length of hospital stay was reduced by 14% for patients admitted to the
      staff-only hospitalist system, compared with the staff/housestaff hospitalist
      system (2.5 and 2.9 days, respectively). This difference remained statistically
      significant after adjustment for age, gender, and comorbidity. There were no
      significant differences between the 2 models of care with respect to subspecialty
      consultation, hospital readmission, or mortality rates. A stratified analysis
      showed similar findings for the 10 most frequent diagnostic groups. CONCLUSIONS:
      The staff-only hospitalist system was associated with a significant reduction in
      the hospital length of stay, without evidence of adverse effects on mortality or
      readmission rates, compared with the staff/hospitalist system. In the context of
      recent restrictions on resident duty hours in the United States, these findings
      may be of interest to pediatric teaching hospitals considering the development of
      a similar staff-only hospitalist model.

PMID- 15574614
TI  - Effects of nurse home-visiting on maternal life course and child development: age
      6 follow-up results of a randomized trial.
AB  - OBJECTIVE: To test, with an urban, primarily black sample, the effects of
      prenatal and infancy home visits by nurses on mothers' fertility and economic
      self-sufficiency and the academic and behavioral adjustment of their children as
      the children finished kindergarten, near their sixth birthday. METHODS: We
      conducted a randomized, controlled trial of a program of prenatal and infancy
      home-visiting in a public system of obstetric and pediatric care in Memphis,
      Tennessee. A total of 743 primarily black women at <29 weeks of gestation, with
      no previous live births and with > or =2 sociodemographic risk characteristics
      (unmarried, <12 years of education, or unemployed), were randomly assigned to
      receive nurse home visits or comparison services. Outcomes consisted of women's
      number and timing of subsequent pregnancies, months of employment, use of
      welfare, food stamps, and Medicaid, educational achievement, behavioral problems
      attributable to the use of substances, rates of marriage and cohabitation, and
      duration of relationships with partners and their children's behavior problems,
      responses to story stems, intellectual functioning, receptive language, and
      academic achievement. RESULTS: In contrast to counterparts assigned to the
      comparison group, women visited by nurses had fewer subsequent pregnancies and
      births (1.16 vs 1.38 pregnancies and 1.08 vs 1.28 births, respectively), longer
      intervals between births of the first and second children (34.28 vs 30.23
      months), longer relationships with current partners (54.36 vs 45.00 months), and,
      since the previous follow-up evaluation at 4.5 years, fewer months of using
      welfare (7.21 vs 8.96 months) and food stamps (9.67 vs 11.50 months). Nurse
      visited children were more likely to have been enrolled in formal out-of-home
      care between 2 and 4.5 years of age (82.0% vs 74.9%). Children visited by nurses
      demonstrated higher intellectual functioning and receptive vocabulary scores
      (scores of 92.34 vs 90.24 and 84.32 vs 82.13, respectively) and fewer behavior
      problems in the borderline or clinical range (1.8% vs 5.4%). Nurse-visited
      children born to mothers with low levels of psychologic resources had higher
      arithmetic achievement test scores (score of 88.61 vs 85.42) and expressed less
      aggression (score of 98.58 vs 101.10) and incoherence (score of 20.90 vs 29.84)
      in response to story stems. There were no statistically significant program
      effects on women's education, duration of employment, rates of marriage, being in
      a partnered relationship, living with the father of the child, or domestic
      violence, current partner's educational level, or behavioral problems
      attributable to the use of alcohol or drugs. CONCLUSION: This program of prenatal
      and infancy home-visiting by nurses continued to improve the lives of women and
      children at child age 6 years, 4 years after the program ended.

PMID- 15574615
TI  - Effects of home visits by paraprofessionals and by nurses: age 4 follow-up
      results of a randomized trial.
AB  - OBJECTIVE: To examine the effects of prenatal and infancy home visiting by
      paraprofessionals and by nurses from child age 2 through age 4 years. METHODS: We
      conducted, in public and private care settings in Denver, Colorado, a randomized,
      controlled trial with 3 arms, ie, control, paraprofessional visits, and nurse
      visits. Home visits were provided from pregnancy through child age 2 years. We
      invited 1178 consecutive, low-income, pregnant women with no previous live births
      to participate, and we randomized 735; 85% were unmarried, 47% Mexican American,
      35% white non-Mexican American, 15% black, and 3% American Indian/Asian. Outcomes
      consisted of maternal reports of subsequent pregnancies, participation in
      education and work, use of welfare, marriage, cohabitation, experience of
      domestic violence, mental health, substance use, and sense of mastery;
      observations of mother-child interaction and the home environment; tests of
      children's language and executive functioning; and mothers' reports of children's
      externalizing behavior problems. RESULTS: Two years after the program ended,
      women who were visited by paraprofessionals, compared with control subjects, were
      less likely to be married (32.2% vs 44.0%) and to live with the biological father
      of the child (32.7% vs 43.1%) but worked more (15.13 months vs 13.38 months) and
      reported a greater sense of mastery and better mental health (standardized scores
      [mean = 100, SD = 10] of 101.25 vs 99.31 and 101.21 vs 99.16, respectively).
      Paraprofessional-visited women had fewer subsequent miscarriages (6.6% vs 12.3%)
      and low birth weight newborns (2.8% vs 7.7%). Mothers and children who were
      visited by paraprofessionals, compared with control subjects, displayed greater
      sensitivity and responsiveness toward one another (standardized score [mean =
      100, SD = 10] of 100.92 vs 98.66) and, in cases in which the mothers had low
      levels of psychologic resources at registration, had home environments that were
      more supportive of children's early learning (score of 24.63 vs 23.35). Nurse
      visited women reported greater intervals between the births of their first and
      second children (24.51 months vs 20.39 months) and less domestic violence (6.9%
      vs 13.6%) and enrolled their children less frequently in preschool, Head Start,
      or licensed day care than did control subjects. Nurse-visited children whose
      mothers had low levels of psychologic resources at registration, compared with
      control group counterparts, demonstrated home environments that were more
      supportive of children's early learning (score of 24.61 vs 23.35), more advanced
      language (score of 91.39 vs 86.73), superior executive functioning (score of
      100.16 vs 95.48), and better behavioral adaptation during testing (score of
      100.41 vs 96.66). There were no statistically significant effects of either nurse
      or paraprofessional visits on the number of subsequent pregnancies, women's
      educational achievement, use of substances, use of welfare, or children's
      externalizing behavior problems. CONCLUSIONS: Paraprofessional-visited mothers
      began to experience benefits from the program 2 years after the program ended at
      child age 2 years, but their first-born children were not statistically
      distinguishable from their control group counterparts. Nurse-visited mothers and
      children continued to benefit from the program 2 years after it ended. The impact
      of the nurse-delivered program on children was concentrated on children born to
      mothers with low levels of psychologic resources.

PMID- 15574616
TI  - Insulin sensitivity among obese children and adolescents, according to degree of
      weight loss.
AB  - OBJECTIVE: Insulin sensitivity is impaired among some obese children, reflecting
      an atherogenic risk factor profile for the affected subjects. This study was
      performed to examine the amount of weight reduction required to improve insulin
      sensitivity. METHODS: We studied changes in insulin sensitivity indices (ISIs)
      for glucose metabolism (homeostasis model assessment and quantitative insulin
      sensitivity check index) and fat metabolism (free fatty acids) during a 1-year
      period among obese children who attended an obesity intervention program. The
      children were divided into 4 groups according to their changes in body mass index
      (BMI) SD score (SDS), as follows: group I, decrease in SDS-BMI of > or =0.5;
      group II, decrease in SDS-BMI of > or =0.25 to <0.5; group III, decrease in SDS
      BMI of <0.25; group IV, increase in SDS-BMI. RESULTS: Fifty-seven obese children
      (age range: 6-14 years; median age: 10 years; 46% boys) were included in the
      study. The 4 groups did not differ with respect to age, gender, degree of
      overweight (SDS-BMI), or ISI values at baseline. An increase in SDS-BMI (group
      IV, n = 12) was followed by a significant decrease in ISI values. The ISIs
      improved for group I (n = 9), whereas there were no significant changes in these
      parameters for group II (n = 21) and group III (n = 15). CONCLUSIONS: During a 1
      year period, an increase in weight among obese children was associated with a
      decrease in insulin sensitivity. Weight loss was followed by significant
      improvement in insulin sensitivity for glucose and fat metabolism but only if the
      SDS-BMI decreased by > or =0.5 during the 1-year period.

PMID- 15574617
TI  - Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone
      density parameters in community-dwelling adolescent girls.
AB  - OBJECTIVE: Anorexia nervosa (AN) is an eating disorder that leads to a number of
      medical sequelae in adult women and has a mortality rate of 5.6% per decade;
      known complications include effects on hematologic, biochemical, bone density,
      and body composition parameters. Few data regarding medical and developmental
      consequences of AN are available for adolescents, in particular for an outpatient
      community-dwelling population of girls who have this disorder. The prevalence of
      AN is increasing in adolescents, and it is the third most common chronic disease
      in adolescent girls. Therefore, it is important to determine the medical effects
      of this disorder in this young population. METHODS: We examined clinical
      characteristics and performed hematologic, biochemical, hormonal, and bone
      density evaluations in 60 adolescent girls with AN (mean age: 15.8 +/- 1.6 years)
      and 58 healthy adolescent girls (mean age: 15.2 +/- 1.8 years) of comparable
      maturity. Nutritional and pubertal status; vital signs; a complete blood count;
      potassium levels; hormonal profiles; bone density at the lumbar and lateral
      spine; total body, hip, and femoral neck (by dual-energy x-ray absorptiometry)
      and body composition (by dual-energy x-ray absorptiometry) were determined.
      RESULTS: All measures of nutritional status such as weight, percentage of ideal
      body weight, body mass index, lean body mass, fat mass, and percentage of fat
      mass were significantly lower in girls with AN than in control subjects. Girls
      with AN had significantly lower heart rates, lower systolic blood pressure, and
      lower body temperature compared with control subjects. Total red cell and white
      cell counts were lower in AN than in control subjects. Among girls with AN, 22%
      were anemic and 22% were leukopenic. None were hypokalemic. Mean age at menarche
      did not differ between the groups. However, the proportion of girls who had AN
      and were premenarchal was significantly higher compared with healthy control
      subjects who were premenarchal, despite comparable maturity as determined by bone
      age. Ninety-four percent of premenarchal girls with AN versus 28% of premenarchal
      control subjects were above the mean age at menarche for white girls, and 35% of
      premenarchal AN girls versus 0% of healthy adolescents were delayed >2 SD above
      the mean. The ratio of bone age to chronological age, a measure of delayed
      maturity, was significantly lower in girls with AN versus control subjects and
      correlated positively with duration of illness and markers of nutritional status.
      Serum estradiol values were lower in girls with AN than in control subjects, and
      luteinizing hormone values trended lower in AN. Levels of insulin-like growth
      factor-I were also significantly lower in girls with AN. Estradiol values
      correlated positively with insulin-like growth factor-I, a measure of nutritional
      status essential for growth (r = 0.28). All measures of bone mineral density (z
      scores) were lower in girls with AN than in control subjects, with lean body
      mass, body mass index, and age at menarche emerging as the most important
      predictors of bone density. Bone density z scores of <-1 at any one site were
      noted in 41% of girls with AN, and an additional 11% had bone density z scores of
      <-2. CONCLUSIONS: A high prevalence of hemodynamic, hematologic, endocrine, and
      bone density abnormalities are reported in this large group of community-dwelling
      adolescent girls with AN. Although a number of these consequences of AN are known
      to occur in hospitalized adolescents, the occurrence of these findings, including
      significant bradycardia, low blood pressure, and pubertal delay, in girls who are
      treated for AN on an outpatient basis is of concern and suggests the need for
      vigilant clinical monitoring, including that of endocrine and bone density
      parameters.

PMID- 15574618
TI  - Declining diagnosis of birth asphyxia in California: 1991-2000.
AB  - OBJECTIVE: Birth asphyxia is recognized as an important cause of neonatal
      morbidity and mortality. Whether advances in perinatal care have altered the
      incidence of birth asphyxia is unknown. We determined the incidence of birth
      asphyxia diagnoses made over a 10-year period in California. METHODS: In a
      population-based retrospective cohort study of 5,364,663 live births, we
      determined the incidence and case fatality of birth asphyxia between 1991 and
      2000. Using a statewide administrative hospital discharge database, we identified
      all newborn admissions that generated a diagnosis of birth asphyxia
      (International Classification of Diseases, Ninth Revision, Clinical Modification
      codes 768.5, 768.6, or 768.9) or a diagnosis that overlaps with birth asphyxia,
      such as congenital encephalopathy or fetal distress. We determined incidence and
      in-hospital case fatality rates adjusted for birth weight and demographic
      characteristics and stratified by associated perinatal complications. RESULTS:
      The 24 330 newborns who received a diagnosis of birth asphyxia yielded a
      population incidence of 4.5 per 1000 live births. Black ethnicity (relative risk
      [RR]: 1.3; 95% confidence interval [CI]: 1.2-1.3), male gender (RR: 1.2; 95% CI:
      1.1-1.2), and low socioeconomic status (RR: 1.2; 95% CI: 1.1-1.2) all were
      associated with increased risk. The diagnosis of birth asphyxia decreased by 91%
      from 14.8 to 1.3 per 1000 live births during the study years. This decrease could
      not be explained by an increased diagnosis of overlapping conditions. Overall
      case fatality was 4%, and the majority of deaths in infants >2000 g occurred in
      the presence of congenital anomalies, cord abnormalities, or maternal hemorrhage.
      In newborns <2000 g, case fatality was highest in the presence of
      chorioamnionitis (48%). CONCLUSION: The diagnosis of birth asphyxia has decreased
      dramatically in recent years. The factors that are responsible for this decline
      are unclear and deserve additional investigation.

PMID- 15574619
TI  - Hypotensive extremely low birth weight infants have reduced cerebral blood flow.
AB  - OBJECTIVES: Whether extremely low birth weight (ELBW) infants are at risk of
      cerebral hypoperfusion is uncertain because key issues concerning their cerebral
      blood flow (CBF) and mean arterial pressure (MAP) are unresolved: (1) whether CBF
      is pressure-passive or autoregulated; (2) the normal level of MAP; and (3)
      whether inotropic drugs used to increase MAP might inadvertently impair CBF. We
      addressed these issues in ELBW infants undergoing intensive care. METHODS: CBF
      (measured by near-infrared spectroscopy) and MAP were measured in 17 infants aged
      1.5 to 40.5 hours. RESULTS: Five infants remained normotensive (MAP 37 +/- 2 mm
      Hg, [mean +/- SEM]); twelve became hypotensive (MAP 25 +/- 1 mm Hg) and were
      treated with dopamine (10-30 mug x kg(-1) per min). CBF of hypotensive infants
      (14 +/- 1 mL x 100 g(-1) per min) was lower than the CBF of normotensive infants
      (19 +/- mL x 100 g(-1) per min). After commencement of dopamine in hypotensive
      infants, MAP increased (29 +/- 1 mm Hg) and CBF also increased (18 +/- 1 mL x
      100g(-1) per min). CBF was correlated with MAP in hypotensive infants before (R =
      0.62) and during (R = 0.67) dopamine, but not in normotensive infants. A
      breakpoint was identified in the CBF versus MAP autoregulation curve of untreated
      infants at MAP = 29 mm Hg; no breakpoint was evident in dopamine-treated infants.
      CONCLUSIONS: In ELBW infants (1) cerebral autoregulation is functional in
      normotensive but not hypotensive infants; (2) a breakpoint exists at
      approximately 30 mm Hg in the CBF-MAP autoregulation curve; and (3) dopamine
      improves both MAP and CBF.

PMID- 15574620
TI  - Randomized, controlled trial of slow versus rapid feeding volume advancement in
      preterm infants.
AB  - OBJECTIVES: To determine whether infants who are fed initially and advanced at 30
      mL/kg per day (intervention) take fewer days to get to full feedings than those
      who are fed initially and advanced at 20 mL/kg per day (control), without
      increasing their incidence of feeding complications and necrotizing enterocolitis
      (NEC). We also examined whether these infants regain birth weight earlier, have
      fewer days of intravenous fluids, and a have shorter hospital stay. METHODS: A
      randomized, controlled, single-center trial was conducted in a Neonatal Intensive
      Care Unit of a community-based county hospital in Houston, Texas. Infants between
      1000 and 2000 g at birth, gestational age < or =35 weeks, and weight appropriate
      for gestational age were allocated randomly to feedings of expressed human milk
      or Enfamil formula starting and advanced at either 30 mL/kg per day or 20 mL/kg
      per day. Infants remained in the study until discharge or development of stage >
      or =IIA NEC. RESULTS: A total of 155 infants were enrolled: 72 infants in the
      intervention group and 83 in the control group. Infants in the intervention group
      achieved full-volume feedings sooner (7 vs 10 days, median), regained birth
      weight faster (11 vs 13 days, median), and had fewer days of intravenous fluids
      (6 vs 8 days, median). Three infants in the intervention group and 2 control
      infants developed NEC for an overall incidence of 3.2% (relative risk: 1.73; 95%
      confidence interval: 0.30-10.06). CONCLUSION: Among infants between 1000 and 2000
      g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a
      safe practice and results in fewer days to reach full-volume feedings than using
      20 mL/kg per day. This intervention also leads to faster weight gain and fewer
      days of intravenous fluids.

PMID- 15574621
TI  - Persistence of benefits of continuous subcutaneous insulin infusion in very young
      children with type 1 diabetes: a follow-up report.
AB  - OBJECTIVE: Use of continuous subcutaneous insulin infusion (CSII) has increased
      dramatically in recent years, and pump therapy has been shown to be a safe and
      effective alternative to multiple daily injections in adults and older pediatric
      patients with type 1 diabetes. Its use in very young children, however, has been
      limited, although this group might be expected to benefit the most from CSII. The
      objective of this study was to analyze the CSII efficacy and safety data in very
      young children with type 1 diabetes from our Diabetes Clinic database. METHODS:
      Glycosylated hemoglobin (HbA1c), severe hypoglycemia (SH), and ketoacidosis (DKA)
      in the year before CSII were compared with corresponding values during pump
      treatment in all children who started CSII before age 7. RESULTS: Sixty-five
      children (mean age: 4.5 y at CSII initiation; range: 1.4-6.9 years; 28 girls; 3
      black, 1 Hispanic) were analyzed for >162 patient-years of follow-up. Mean
      HbA(1c) (7.4 +/- 1.0 prepump) decreased to 7.0 +/- 0.9 after 12 months of CSII
      and continued to improve even after 4 years on CSII. The rate of SH was reduced
      by 53% (from 78 to 37/100 patient-years). Children who received daytime care from
      paid caregivers (n = 26) experienced significant reductions in HbA1c and
      hypoglycemia frequency. There were no episodes of DKA requiring emergency
      treatment in the year before CSII and 4 episodes (4 per 100 patient-years) after
      transition to pump. CONCLUSIONS: CSII is a durable and effective means of
      optimizing glycemic control in very young patients with type 1 diabetes and may
      be superior to multiple daily injections in minimizing the risk of severe
      hypoglycemia in this age group. Employment of paid caregivers does not preclude
      safe and effective use of CSII.

PMID- 15574622
TI  - Economic analysis of palivizumab in infants with congenital heart disease.
AB  - OBJECTIVE: Palivizumab has been shown to reduce the number of respiratory
      syncytial virus (RSV)-related hospitalizations by 45% in children with congenital
      heart disease (CHD). The American Academy of Pediatrics has recommended that
      infants with hemodynamically significant CHD be considered for palivizumab.
      However, the economic implications of palivizumab prophylaxis in the CHD
      population have not been evaluated. In the present study, we sought to examine
      the cost savings and cost utility of RSV prophylaxis with palivizumab in children
      with CHD. METHODS: Probabilities of hospitalization and efficacy of prophylaxis
      were based on published results. Costs of hospitalization were derived from a
      published analysis of bronchiolitis hospitalization costs from a consortium of
      children's hospitals. A hypothetical cohort of 10,000 CHD patients (half of whom
      would receive palivizumab) was created to calculate cost-savings and cost
      utility. To assess cost utility, we assumed that by reducing hospitalization,
      palivizumab would reduce RSV-related hospital mortality, generally reported to be
      3% in CHD patients. Sensitivity analysis was performed. RESULTS: On the basis of
      a protocol of 5 monthly doses of palivizumab, the cost of prophylaxis for 1 RSV
      season was calculated as 6160 dollars per patient. After accounting for impact on
      direct and indirect costs of hospitalization, administration of palivizumab to
      5000 CHD patients would result in a net loss of 20,415,753 dollars. If one
      assumes that palivizumab confers a survival benefit, then the cost of life-year
      saved is 100,338 dollars and cost of quality-adjusted life-year saved is 114,337
      dollars. CONCLUSIONS: The cost of palivizumab prophylaxis was high relative to
      benefits realized. Given the large number of CHD patients who might be considered
      candidates for RSV prophylaxis (>6000 patients per year in United States) routine
      use of palivizumab in young children with hemodynamically significant CHD needs
      to be evaluated further.

PMID- 15574623
TI  - Direct cost analyses of palivizumab treatment in a cohort of at-risk children:
      evidence from the North Carolina Medicaid Program.
AB  - OBJECTIVE: Use of palivizumab prophylactic therapy reduces the occurrence of
      hospitalizations for serious respiratory syncytial virus (RSV) lower respiratory
      tract infections in at-risk infants. The direct cost-benefit of palivizumab
      prophylaxis for infants who are born at 32 to 35 weeks' estimated gestational age
      (EGA) during their first year of life has not been systematically examined. The
      objective of this study was to compare the direct costs of palivizumab
      prophylaxis and RSV treatment in infants who were born at 32 to 35 weeks EGA and
      received and did not receive palivizumab. METHODS: A cohort study was performed
      of infants who were younger than 1 year and were enrolled in an enhanced primary
      care case management model within the North Carolina Medicaid Program.
      Comparisons were made between infants who received (Synagis prophylaxis group)
      and did not receive palivizumab (nonprophylaxis group) during the study period.
      Cost was examined using the sum of Medicaid paid services for prophylaxis with
      palivizumab and treatment for RSV infections that occurred between October 1,
      2002, and May 31, 2003. The Anderson framework was used to specify the regression
      cost models to compare the participants who received (Synagis prophylaxis) and
      did not receive (nonprophylaxis group) palivizumab. The primary outcomes were
      actual 7-month seasonal costs and standardized seasonal costs adjusting for the
      varied months of infant participation. RESULTS: The study sample included 185
      Synagis prophylaxis and 182 nonprophylaxis participants who met the inclusion
      criteria. The average per-person total cost of RSV care and prophylaxis was 5117
      dollars for the Synagis prophylaxis group and 371 dollars for the nonprophylaxis
      group. Five hospitalizations occurred in the prophylaxis group, and 12 occurred
      in the nonprophylaxis group (odds ratio: 0.27). No deaths occurred in either
      group. CONCLUSIONS: Palivizumab administered to infants who were born at 32 to 35
      weeks' EGA did not provide direct cost savings related to hospitalization or
      ambulatory care in a Medicaid population. The primary difference in cost between
      the groups was attributable to the palivizumab prophylaxis.

PMID- 15574624
TI  - End-of-life after birth: death and dying in a neonatal intensive care unit.
AB  - OBJECTIVE: In canonical modern bioethics, withholding and withdrawing medical
      interventions for dying patients are considered morally equivalent. However,
      electing not to administer cardiopulmonary resuscitation (CPR) struck us as
      easily distinguishable from withdrawing mechanical ventilation. Moreover,
      withdrawing mechanical ventilation from a moribund infant "feels" different from
      withdrawing mechanical ventilation from a hemodynamically stable child with a
      severe neurologic insult. Most previous descriptions of withdrawing and
      withholding intervention in the neonatal intensive care unit (NICU) have blurred
      many of these distinctions. We hypothesized that clarifying them would more
      accurately portray the process of end-of-life decision-making in the NICU.
      METHODS: We reviewed the charts of all newborn infants who had birth weight >400
      g and died in our hospital in 1988, 1993, and 1998 and extracted potential
      ethical issues (resuscitation, withdrawal, withholding, CPR, do-not-resuscitate
      orders, neurologic prognosis, ethics consult) surrounding each infant's death.
      RESULTS: Using traditional definitions, roughly half of all deaths in our NICU in
      1993 and 1998 were associated with "withholding or withdrawing." In addition, by
      1998, >40% of our NICU deaths could be labeled "active withdrawal," reflecting
      the extubation of infants regardless of their physiologic instability. This
      practice is growing over time. However, 2 important conclusions arise from our
      more richly elaborated descriptions of death in the NICU. First, when CPR was
      withheld, it most commonly occurred in the context of moribund infants who were
      already receiving ventilation and dopamine. Physiologically stable infants who
      were removed from mechanical ventilation for quality-of-life reasons accounted
      for only 3% of NICU deaths in 1988, 16% of NICU deaths in 1993, and 13% of NICU
      deaths in 1998. Moreover, virtually none of these active withdrawals took place
      in premature infants. Second, by 1998 infants, who died without CPR almost always
      had mechanical ventilation withdrawn. Finally, the median and average day of
      death for 100 nonsurvivors who received full intervention did not differ
      significantly from the 78 nonsurvivors for whom intervention was withheld.
      CONCLUSIONS: In our unit, a greater and greater percentage of doomed infants die
      without ever receiving chest compressions or epinephrine boluses. Rather, we have
      adopted a nuanced approach to withdrawing/withholding NICU intervention,
      providing what we hope is a humane approach to end-of-life decisions for doomed
      NICU infants. We suggest that ethical descriptions that reflect these nuances,
      distinguishing between withholding and withdrawing interventions from
      physiologically moribund infants or physiologically stable infants with morbid
      neurologic prognoses, provide a more accurate reflection of the circumstances of
      dying in the NICU.

PMID- 15574625
TI  - Benefits of the nonfasting ketogenic diet compared with the initial fasting
      ketogenic diet.
AB  - OBJECTIVE: The ketogenic diet (KD) is traditionally introduced with an initial
      period of fasting and fluid restriction that is difficult and sometimes
      complicated by moderate dehydration. This investigation compares the efficacy and
      tolerability of the nonfasting ketogenic diet (NFKD) and the conventional initial
      fasting ketogenic diet (IFKD). METHODS: Forty-one children with intractable
      epilepsy were treated with the NFKD, beginning with a gradual increase in
      calories with no initial fasting or fluid restriction. This NFKD population was
      compared retrospectively with 83 recent historical control subjects who were
      treated with the IFKD. Efficacy, tolerability, time until strong ketosis, and
      occurrence of complications were compared. RESULTS: Fourteen (34.1%) patients
      became seizure-free for at least 3 months after the NFKD, compared with 29
      (34.9%) after the IFKD. There was no significant difference in days until strong
      urinary ketosis between the 2 groups. The incidence of hypoglycemia was also not
      significantly different between the groups as most other laboratory findings,
      although the blood urea nitrogen was elevated in 24.1% of the IFKD group and in
      only 12.2% of the NFKD patients without statistical significance. Conversely,
      moderate dehydration was significantly less frequent in the NFKD group (12.2%)
      than in the IFKD group (62.7%). Finally, these results were reflected to the
      shortening of the hospitalization period in the NFKD group. CONCLUSIONS: These
      observations suggest that initial fasting and fluid restriction are not essential
      for the KD and that the tolerability of this treatment may be improved. These
      data support our intention to conduct a formal, prospective, randomized trial
      comparing 2 forms of the KD.

PMID- 15574626
TI  - Paternity after adolescent varicocele repair.
AB  - OBJECTIVE: Varicocelectomy has long been a therapeutic modality used in the
      treatment of male infertility. In the past decade, adolescent varicocelectomy has
      become a frequent procedure to preserve testicular growth and to help prevent
      future infertility. Because our clinical population includes a large portion of
      orthodox Jews who traditionally marry early and are forbidden to use birth
      control by religious law, we thought that by studying our patients, we might be
      able to accelerate our follow-up regarding paternity. In addition, we wanted to
      learn whether adolescent varicocelectomy might have any negative impact. METHODS:
      Questionnaires inquiring as to the marital and paternity status, postoperative
      course, and complications were sent to 50 patients who had undergone a unilateral
      or bilateral varicocele repair during adolescence and who were at least 21 years
      old at the time of this review. In addition, a careful chart review was performed
      to examine the perioperative and postoperative parameters of each respondent.
      RESULTS: Of the 43 responses (86% response rate), 18 of 18 patients who had
      attempted to father a child were successful. The remaining 25 were not married or
      had never attempted to father a child. In the paternity group, 10 of the fathers
      had undergone an Ivanissevich repair; the remaining 8 had a Palomo repair.
      Sixteen of the 18 had unilateral varicocelectomies, and 2 underwent bilateral
      repairs. Of those with a unilateral varicocele, the indication for surgery in 10
      was a grade 2 to 3 varicocele associated with a >20% volume difference when
      compared with the right testicle. Three had 10% to 20% volume loss, whereas the
      remaining three had unusually large grade 3 varicoceles without concurrent volume
      difference. CONCLUSIONS: Varicocelectomy in the adolescent population has been
      proposed as a therapeutic intervention to preserve both fertility and testicular
      growth. Although not showing a cause-and-effect relationship, it is our
      contention that varicocelectomy in adolescence at worst does no harm and at best
      preserves fertility.

PMID- 15574627
TI  - Influence of sleep position experience on ability of prone-sleeping infants to
      escape from asphyxiating microenvironments by changing head position.
AB  - OBJECTIVE: Several studies have found that back- or side-sleeping infants who are
      inexperienced in prone sleeping are at much higher risk for sudden infant death
      syndrome (SIDS) when they turn to prone or are placed prone for sleep compared
      with infants who normally sleep prone. Moreover, such inexperienced infants are
      more likely to be found in the face-down position at death after being placed
      prone compared with SIDS infants who are experienced in prone sleeping. We
      hypothesized that lack of experience in prone sleeping is associated with
      increased difficulty in changing head position to avoid an asphyxiating sleep
      environment. METHODS: We studied 38 healthy infants while they slept prone. Half
      of these were experienced and half were inexperienced in prone sleeping. To
      create a mildly asphyxiating microenvironment, we placed infants to sleep prone
      with their faces covered by soft bedding. We recorded inspired CO2 (CO2I),
      electrocardiogram, and respiration, and we videotaped head movements. Also, we
      assessed gross motor development (Denver Development Scale). RESULTS: When
      sleeping prone, with their faces covered by bedding, all infants experienced mild
      asphyxia as a result of rebreathing. All aroused and attempted escape from this
      environment. Infants used 3 stereotyped head-repositioning strategies. The least
      effective was nuzzling into the bedding with occasional brief head lifts. More
      effective were head lifts combined with a head turn. Some infants, however, could
      turn only to 1 side, right or left. Infants who were inexperienced in prone
      sleeping had less effective protective behaviors than experienced infants. Infant
      age did not correlate with efficacy of protective behaviors. Infants who were
      experienced in prone sleep had advanced gross motor development compared with
      inexperienced infants. CONCLUSION: Infants who are inexperienced in prone
      sleeping have decreased ability to escape from asphyxiating sleep environments
      when placed prone. These observations potentially explain the increased risk
      associated with prone sleep in infants who are inexperienced. The increased
      occurrence of the face-down position in such infants is also potentially
      explained. These findings suggest that airway protective behaviors may be
      acquired through the mechanism of operant conditioning (learning).

PMID- 15574628
TI  - Increased behavioral morbidity in school-aged children with sleep-disordered
      breathing.
AB  - OBJECTIVE: To assess whether sleep-disordered breathing (SDB), ranging from
      primary snoring to obstructive sleep apnea (OSA), is associated with increased
      behavioral morbidity. METHODS: A cross-sectional study was conducted of school
      aged children in an urban, community-based cohort, stratified for term or preterm
      (<37 weeks' gestation) birth status. A total of 829 children, 8 to 11 years old
      (50% female, 46% black, 46% former preterm birth) were recruited from a cohort
      study. All children had unattended in-home overnight cardiorespiratory recordings
      of airflow, respiratory effort, oximetry, and heart rate for measurement of the
      apnea hypopnea index (number of obstructive apneas and hypopneas per hour). SDB
      was defined by either parent-reported habitual snoring or objectively measured
      OSA. Functional outcomes were assessed with 2 well-validated parent ratings of
      behavior problems: the Child Behavioral Checklist and the Conners Parent Rating
      Scale-Revised:Long. RESULTS: Forty (5%) children were classified as having OSA
      (median apnea hypopnea index: 7.1 per hour; interquartile range: 3.1-10.5), 122
      (15%) had primary snoring without OSA, and the remaining 667 (80%) had neither
      snoring nor OSA. Children with SDB had significantly higher odds of elevated
      problem scores in the following domains: externalizing, hyperactive, emotional
      lability, oppositional, aggressive, internalizing, somatic complaints, and social
      problems. CONCLUSIONS: Children with relatively mild SDB, ranging from primary
      snoring to OSA, have a higher prevalence of problem behaviors, with the
      strongest, most consistent associations for externalizing, hyperactive-type
      behaviors.

PMID- 15574629
TI  - Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia:
      a multicenter trial.
AB  - BACKGROUND: Infants developing bronchopulmonary dysplasia (BPD) show decreased
      cortisol response to adrenocorticotropic hormone. A pilot study of low-dose
      hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed
      improved survival without BPD at 36 weeks' postmenstrual age, particularly in
      infants exposed to histologic chorioamnionitis. METHODS: Mechanically ventilated
      infants with birth weights of 500 to 999 g were enrolled into this multicenter,
      randomized, masked trial between 12 and 48 hours of life. Patients received
      placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day
      for 3 days. BPD at 36 weeks' postmenstrual age was defined clinically (receiving
      supplemental oxygen) and physiologically (supplemental oxygen required for O2
      saturation > or =90%). RESULTS: Patient enrollment was stopped at 360 patients
      because of an increase in spontaneous gastrointestinal perforation in the
      hydrocortisone-treated group. Survival without BPD was similar, defined
      clinically or physiologically, as were mortality, head circumference, and weight
      at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149),
      hydrocortisone treatment significantly decreased mortality and increased survival
      without BPD, defined clinically or physiologically. After treatment, cortisol
      values and response to adrenocorticotropic hormone were similar between groups.
      Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal
      perforations than placebo-treated infants receiving indomethacin, suggesting an
      interactive effect. CONCLUSIONS: Prophylaxis of early adrenal insufficiency did
      not improve survival without BPD in the overall study population; however,
      treatment of chorioamnionitis-exposed infants significantly decreased mortality
      and improved survival without BPD. Low-dose hydrocortisone therapy did not
      suppress adrenal function or compromise short-term growth. The combination of
      indomethacin and hydrocortisone should be avoided.

PMID- 15574630
TI  - The adolescent varicocele.

PMID- 15574631
TI  - Early closure of the Watterberg trial.

PMID- 15574632
TI  - A delay in publication of the "Annual Summary of Vital Statistics" and the need
      for new vital registration and statistics systems for the United States.

PMID- 15574633
TI  - Spectrum of clinical manifestations of West Nile virus infection in children.
AB  - Reports of clinical manifestations of West Nile virus (WNV) infections in
      children have been relatively rare. Four cases of WNV infection in children are
      described: the first report of prolonged encephalitis and fulminant hepatitis
      caused by WNV, and 3 other presentations of WNV, including the first report of
      ocular involvement in a child.

PMID- 15574634
TI  - Role of pediatricians in advocating life support training courses for parents and
      the public.
AB  - Available literature suggests a need for both initial cardiopulmonary
      resuscitation basic life support training and refresher courses for parents and
      the public as well as health care professionals. The promotion of basic life
      support training courses that establish a pediatric chain of survival spanning
      from prevention of cardiac arrest and trauma to rehabilitative and follow-up care
      for victims of cardiopulmonary arrest is advocated in this policy statement and
      is the focus of an accompanying technical report. Immediate bystander
      cardiopulmonary resuscitation for victims of cardiac arrest improves survival for
      out-of-hospital cardiac arrest. Pediatricians will improve the chance of survival
      of children and adults who experience cardiac arrest by advocating for
      cardiopulmonary resuscitation training and participating in basic life support
      training courses as participants and instructors.

PMID- 15574635
TI  - Ensuring culturally effective pediatric care: implications for education and
      health policy.
AB  - This policy statement defines culturally effective health care and describes its
      importance for pediatrics and the health of children. The statement also defines
      cultural effectiveness, cultural sensitivity, and cultural competence and
      describes the importance of these concepts for training in medical school,
      residency, and continuing medical education. The statement is based on the
      conviction that culturally effective health care is vital and a critical social
      value and that the knowledge and skills necessary for providing culturally
      effective health care can be taught and acquired through focused curricula
      throughout the spectrum of lifelong learning, from premedical education and
      medical school through residency and continuing medical education. The American
      Academy of Pediatrics also believes that these educational efforts must be
      supported through health policy and advocacy activities that promote the delivery
      of culturally effective pediatric care.

PMID- 15574636
TI  - Do-not-resuscitate orders for pediatric patients who require anesthesia and
      surgery.
AB  - This clinical report addresses the topic of preexisting do-not-resuscitate (DNR)
      orders for children undergoing anesthesia and surgery. Pertinent issues addressed
      include the rights of children, surrogate decision-making, the process of
      informed consent, and the roles of surgeons and anesthesiologists. The
      reevaluation process of DNR orders called "required reconsideration" can be
      incorporated into the process of informed consent for surgery and anesthesia.
      Care should be taken to distinguish between goal-directed and procedure-directed
      approaches to DNR orders. By giving parents or other surrogates and clinicians
      the option of deciding from among full resuscitation, limitations based on
      procedures, or limitations based on goals, the child's needs are individualized
      and better served.

PMID- 15574637
TI  - Managed care and children with special health care needs.
AB  - The implementation of managed care for children with special health care needs is
      often associated with apprehension regarding new barriers to health care
      services. At times, these barriers may overshadow opportunities for improvement.
      This statement discusses such opportunities, identifies challenges, and proposes
      active roles for pediatricians and families to improve managed care for children
      with special health care needs.

PMID- 15574638
TI  - Ambient air pollution: health hazards to children.
AB  - Ambient (outdoor) air pollution is now recognized as an important problem, both
      nationally and worldwide. Our scientific understanding of the spectrum of health
      effects of air pollution has increased, and numerous studies are finding
      important health effects from air pollution at levels once considered safe.
      Children and infants are among the most susceptible to many of the air
      pollutants. In addition to associations between air pollution and respiratory
      symptoms, asthma exacerbations, and asthma hospitalizations, recent studies have
      found links between air pollution and preterm birth, infant mortality, deficits
      in lung growth, and possibly, development of asthma. This policy statement
      summarizes the recent literature linking ambient air pollution to adverse health
      outcomes in children and includes a perspective on the current regulatory
      process. The statement provides advice to pediatricians on how to integrate
      issues regarding air quality and health into patient education and children's
      environmental health advocacy and concludes with recommendations to the
      government on promotion of effective air-pollution policies to ensure protection
      of children's health.

PMID- 15574639
TI  - Diagnosis, treatment, and long-term management of Kawasaki disease: a statement
      for health professionals from the Committee on Rheumatic Fever, Endocarditis, and
      Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart
      Association.
AB  - BACKGROUND: Kawasaki disease is an acute self-limited vasculitis of childhood
      that is characterized by fever, bilateral nonexudative conjunctivitis, erythema
      of the lips and oral mucosa, changes in the extremities, rash, and cervical
      lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately
      15% to 25% of untreated children and may lead to ischemic heart disease or sudden
      death. METHODS AND RESULTS: A multidisciplinary committee of experts was convened
      to revise the American Heart Association recommendations for diagnosis,
      treatment, and long-term management of Kawasaki disease. The writing group
      proposes a new algorithm to aid clinicians in deciding which children with fever
      for > or =5 days and < or =4 classic criteria should undergo echocardiography
      [correction], receive intravenous gamma globulin (IVIG) treatment, or both for
      Kawasaki disease. The writing group reviews the available data regarding the
      initial treatment for children with acute Kawasaki disease, as well for those who
      have persistent or recrudescent fever despite initial therapy with IVIG,
      including IVIG retreatment and treatment with corticosteroids, tumor necrosis
      factor-alpha antagonists, and abciximab. Long-term management of patients with
      Kawasaki disease is tailored to the degree of coronary involvement;
      recommendations regarding antiplatelet and anticoagulant therapy, physical
      activity, follow-up assessment, and the appropriate diagnostic procedures to
      evaluate cardiac disease are classified according to risk strata. CONCLUSIONS:
      Recommendations for the initial evaluation, treatment in the acute phase, and
      long-term management of patients with Kawasaki disease are intended to assist
      physicians in understanding the range of acceptable approaches for caring for
      patients with Kawasaki disease. The ultimate decisions for case management must
      be made by physicians in light of the particular conditions presented by
      individual patients.

PMID- 15574641
TI  - Neurologic disorders in patients with celiac disease: are they mediated by brain
      perfusion changes?

PMID- 15574642
TI  - Rethinking well-child care: lack of standardization at the beginning.

PMID- 15574643
TI  - Rethinking well-child care: lack of standardization at the beginning.

PMID- 15574644
TI  - Rethinking well-child care.

PMID- 15574646
TI  - Mortality among Kenyan children admitted to a rural district hospital on weekends
      as compared with weekdays.

PMID- 15574647
TI  - Early intervention in preterm infants after discharge from hospital.

PMID- 15574649
TI  - Findings from selective serotonin reuptake inhibitor-exposed neonates should be
      interpreted with caution.

PMID- 15574652
TI  - Bilirubin the beneficent.

PMID- 15574653
TI  - Hospital-acquired hyponatremia.

PMID- 15574655
TI  - Hospital-acquired hyponatremia is associated with excessive administration of
      intravenous maintenance fluid.

PMID- 15574656
TI  - Severe extrapyramidal symptoms in a 3-year-old boy after accidental ingestion of
      the new antipsychotic drug aripiprazole.

PMID- 15574658
TI  - Sex, lies, and strategic interference: the psychology of deception between the
      sexes.
AB  - The desires of one sex can lead to deceptive exploitation by the other sex.
      Strategic Interference Theory proposes that certain "negative" emotions evolved
      or have been co-opted by selection, in part, to defend against deception and
      reduce its negative consequences. In Study 1 (N = 217) Americans reported
      emotional distress in response to specific forms of deception. Study 2 (N = 200)
      replicated the results in a German sample. Study 3 (N = 479) assessed Americans'
      past experiences with deception and conducted additional hypothesis tests using a
      procedure to control for overall sex differences in upset. Each study supported
      the hypothesis that emotions track sex-linked forms of strategic interference.
      Three clusters of sex differences proved robust across studies-emotional upset
      about resource deception, commitment deception, and sexual deception. We discuss
      implications for theories of mating and emotion and directions for research based
      on models of antagonistic coevolution between the sexes.

PMID- 15574659
TI  - The impact of fear appeals on processing and acceptance of action
      recommendations.
AB  - A stage model of processing of fear-arousing communications was tested in an
      experiment that examined the impact of vulnerability to a severe health risk, the
      quality of the arguments supporting a protective action recommendation, and the
      source to which the recommendation was attributed, on processing and acceptance
      of the recommendation. Argument quality influenced attitudes toward the
      recommendation (but not intention to act), and this effect was mediated by
      negative thoughts about the recommendation. Vulnerability influenced intention to
      act (but not attitudes), and this effect was mediated by perceived threat and
      positive thoughts about the recommendation. The pattern of findings suggests that
      although vulnerability to a severe health risk induces biased processing of the
      recommendation, biased processing is restricted to intentions and does not
      compromise the evaluation of the recommendation. The theoretical and practical
      implications of these findings are discussed.

PMID- 15574660
TI  - Stereotype content model explains prejudice for an envied outgroup: Scale of anti
      Asian American Stereotypes.
AB  - The Stereotype Content Model hypothesizes anti-Asian American stereotypes
      differentiating two dimensions: (excessive) competence and (deficient)
      sociability. The Scale of Anti-Asian American Stereotypes (SAAAS) shows this
      envious mixed prejudice in six studies. Study 1 began with 131 racial attitude
      items. Studies 2 and 3 tested 684 respondents on a focused 25-item version.
      Studies 4 and 5 tested the final 25-item SAAAS on 222 respondents at three
      campuses; scores predicted outgroup friendships, cultural experiences, and
      (over)estimated campus presence. Study 6 showed that allegedly low sociability,
      rather than excessively high competence, drives rejection of Asian Americans,
      consistent with system justification theory. The SAAAS demonstrates mixed,
      envious anti-Asian American prejudice, contrasting with more-often-studied
      contemptuous racial prejudices (i.e., against Blacks).

PMID- 15574661
TI  - Cross-cultural differences in relationship- and group-based trust.
AB  - Two experiments explored differences in depersonalized trust (trust toward a
      relatively unknown target person) across cultures. Based on a recent theoretical
      framework that postulates predominantly different bases for group behaviors in
      Western cultures versus Eastern cultures, it was predicted that Americans would
      tend to trust people primarily based on whether they shared category memberships;
      however, trust for Japanese was expected to be based on the likelihood of sharing
      direct or indirect interpersonal links. Results supported these predictions. In
      both Study 1 (questionnaire study) and Study 2 (online money allocation game),
      Americans trusted ingroup members more than outgroup members; however, the
      existence of a potential indirect relationship link increased trust for outgroup
      members more for Japanese than for Americans. Implications for understanding
      group processes across cultures are discussed.

PMID- 15574662
TI  - Darwinian grandparenting: preferential investment in more certain kin.
AB  - Studies on grandparental investment have revealed that mothers' fathers are
      emotionally closer to their grandchildren than are fathers' mothers. In the
      current study, it was hypothesized that this difference is caused by the fact
      that fathers' mothers often have the potential to invest in genetically more
      certain kin (children through their daughters). To test this hypothesis, 787
      participants rated their emotional closeness and exposure to their grandparents
      and indicated whether they had cousins through paternal and maternal aunts and
      uncles. Results indicated that participants felt closer to mothers' fathers than
      fathers' mothers only when alternate investment outlets for fathers' mothers were
      available. Closeness ratings to fathers' fathers also were reduced when they had
      grandchildren through their daughters. Exposure to grandparents revealed a
      similar pattern of findings but did not show the same sensitivity to the presence
      of more certain kin and did not appear to account for the closeness ratings.

PMID- 15574663
TI  - Why do fear and anger look the way they do? Form and social function in facial
      expressions.
AB  - The origins of the appearances of anger and fear facial expressions are not well
      understood. The authors tested the hypothesis that such origins might lie in the
      expressions' resemblance to, respectively, mature and babyish faces in three
      studies. In Study 1, faces expressing anger and fear were judged to physically
      resemble mature and babyish faces. Study 2 indicated that characteristics
      associated specifically with babyishness are attributed to persons showing fear,
      whereas characteristics associated with maturity are attributed to persons
      showing anger. In Study 3, composite faces were used to minimize the possibility
      that the attributions were based on associations to the anger and fear emotions
      alone rather than to the physical resemblance of the expressions to static facial
      appearance cues. These results suggest that fear and anger expressions may serve
      socially adaptive purposes for those who show them, similar to the social
      adaptations associated with a babyish or mature facial appearance.

PMID- 15574664
TI  - The interplay between goal intentions and implementation intentions.
AB  - Two studies tested whether action control by implementation intentions is
      sensitive to the activation and strength of participants' underlying goal
      intentions. In Study 1, participants formed implementation intentions (or did
      not) and their goal intentions were measured. Findings revealed a significant
      interaction between implementation intentions and the strength of respective goal
      intentions. Implementation intentions benefited the rate of goal attainment when
      participants had strong goal intentions but not when goal intentions were weak.
      Study 2 activated either a task-relevant or a neutral goal outside of
      participants' conscious awareness and found that implementation intentions
      affected performance only when the relevant goal had been activated. These
      findings indicate that the rate of goal attainment engendered by implementation
      intentions takes account of the state (strength, activation) of people's
      superordinate goal intentions.

PMID- 15574665
TI  - Perceptions of entitativity and attitude change.
AB  - The current work explored the properties of groups that lead them to be
      persuasive and the processes through which such persuasion occurs. Because more
      entitative groups induce greater levels of information processing, their
      arguments should receive greater elaboration, leading to persuasion when members
      of groups present strong (vs. weak) counter attitudinal arguments. Experiment 1
      explored these hypotheses by examining if idiosyncratic perceptions of group
      entitativity and manipulations of argument strength affect attitude change and
      argument elaboration. Experiment 2 experimentally manipulated group entitativity
      and argument strength independently to examine the causal relationship between
      entitativity, attitude change, and argument elaboration. In both experiments, it
      was found that groups greater in entitativity were more persuasive when
      presenting strong (vs. weak) arguments and induced greater argument elaboration.
      Implications for our understanding of entitativity, persuasion, and information
      processing about social groups are discussed.

PMID- 15574666
TI  - Engagement and arousal: optimism's effects during a brief stressor.
AB  - Optimism is usually associated with better psychological and physiological
      adjustment to stressors, but some contradictory findings exist. The purpose of
      this study was to investigate how optimism could result in negative immunological
      changes following difficult stressors. Because optimists are likely to see
      positive outcomes as attainable, they may invest greater effort to achieve their
      goals. It is proposed that such engagement would be more physiologically
      demanding when pursuing difficult goals. Participants (N = 54) worked on 11
      difficult or insoluble anagrams. Optimism when combined with high self-awareness
      increased time spent working on the anagrams and skin conductance and salivary
      cortisol during the recovery period. The results support the notion that the
      increased engagement that arises from optimism may lead to short-term
      physiological costs.

PMID- 15574667
TI  - Unconscious affective reactions to masked happy versus angry faces influence
      consumption behavior and judgments of value.
AB  - The authors explored three properties of basic, unconsciously triggered affective
      reactions: They can influence consequential behavior, they work without eliciting
      conscious feelings, and they interact with motivation. The authors investigated
      these properties by testing the influence of subliminally presented happy versus
      angry faces on pouring and consumption of beverage (Study 1), perception of
      beverage value (Study 2), and reports of conscious feelings (both studies).
      Consistent with incentive motivation theory, the impact of affective primes on
      beverage value and consumption was strongest for thirsty participants. Subliminal
      smiles caused thirsty participants to pour and consume more beverage (Study 1)
      and increased their willingness to pay and their wanting more beverage (Study 2).
      Subliminal frowns had the opposite effect. No feeling changes were observed, even
      in thirsty participants. The results suggest that basic affective reactions can
      be unconscious and interact with incentive motivation to influence assessment of
      value and behavior toward valenced objects.

PMID- 15574668
TI  - Adult attachment dimensions and specificity of emotional distress symptoms:
      prospective investigations of cognitive risk and interpersonal stress generation
      as mediating mechanisms.
AB  - Three prospective studies examined the relation between adult attachment
      dimensions and symptoms of emotional distress (anxiety and depression). Across
      all three studies, avoidant and anxious attachment prospectively predicted
      depressive symptoms, and anxious attachment was associated concurrently with
      anxiety symptoms. Study 2 tested a cognitive risk factors mediational model, and
      Study 3 tested an interpersonal stress generation mediational model. Both
      cognitive and interpersonal mediating processes were supported. The cognitive
      risk factors pathway, including elevated dysfunctional attitudes and low self
      esteem, specifically mediated the relation between insecure attachment and
      prospective elevations in depression but not anxiety. For the interpersonal
      stress generation model, experiencing additional interpersonal, but not
      achievement, stressors over time mediated the association between insecure
      attachment and prospective elevations in depressive and anxious symptoms. Results
      advance theory and empirical knowledge about why these interpersonal and
      cognitive mechanisms explain how insecurely attached people become depressed and
      anxious.

PMID- 15574670
TI  - Predicting wife assault: a critical review and implications for policy and
      practice.
AB  - In this review, the authors examine the research evidence for the prediction of
      wife assault recidivism, lethal wife assault, and wife assault onset. They also
      review and present original data on the effect of treatment attendance on wife
      assault risk. Violence does not always become a stable habit, and variables
      associated with wife assault onset do not necessarily predict recidivism. General
      antisociality, psychopathy, substance abuse, and a history of assault and
      psychological abuse in the relationship are the most promising predictors of
      recidivism. Formal risk assessments, and victims' predictions, have demonstrated
      value in predicting recidivism. The authors review existing assessments for wife
      assault onset and recidivism and explain the relative merits of actuarial tools
      and structured clinical assessments. Because of statistical and practical
      limitations to predicting lethal assault, they recommend using an actuarial
      assessment of wife assault risk, plus attention to the strongest correlates of
      lethal assault when lethality is a concern.

PMID- 15574671
TI  - Mediators of the link between childhood sexual abuse and emotional distress: a
      critical review.
AB  - A history of childhood sexual abuse (CSA) is a risk factor for adult emotional
      distress, including symptoms of depression, anxiety, dissociation, and trauma.
      However, CSA is likely associated with adult distress indirectly through an
      impact on mediating variables. In a review of the empirical literature, the
      authors found support for the roles of shame or self-blame, interpersonal
      difficulties, and avoidant coping strategies as mediators. In addition, emotional
      distress appears to mediate links between CSA and other adverse outcomes, such as
      alcohol abuse and revictimization. The authors conclude with a number of
      methodological and conceptual recommendations.

PMID- 15574672
TI  - Family violence among adults with severe mental illness: a neglected area of
      research.
AB  - Violence against family caregivers by their adult relatives with severe mental
      illness is a taboo area of public discourse and scientific research because of
      fears of further stigmatizing this population. Yet, these families experience
      violence at a rate estimated to be between 10% and 40%, which is considerably
      higher than the general population. This article reviews the limited research on
      violence of adults with severe mental illness against their family caregivers and
      proposes a conceptual framework that can further stimulate study in an area that
      has been neglected too long by both mental health and family violence
      investigators. Research on this topic is essential in developing effective policy
      and practice interventions.

PMID- 15574673
TI  - Assessment and screening tools for trauma in children and adolescents: a review.
AB  - The need for thorough and accurate assessment of trauma in the lives of children
      and adolescents has become extremely important for the implementation of
      appropriate interventions. This article reviews 35 measures, 25 in depth and 10
      in brief, that are currently available for use by researchers and practitioners.
      Instruments were divided into four domains: those that screen for (1) both a
      history of exposure to traumatic events and the presence of symptoms of trauma;
      (2) only a history of exposure; (3) symptoms of posttraumatic stress disorder
      (PTSD) or Dissociations; and (4) multiple symptoms of trauma (i.e. depressions,
      anger, sexual concerns, as well as PTSD). Information about the type of
      instrument, how trauma is constructed, psychometric properties, and practical
      issues are addressed for each of the 25 measures. A brief analysis is also
      provided for each measure.

PMID- 15574674
TI  - Dietary exposure to aroclor 1254 alters central and peripheral vasopressin
      release in response to dehydration in the rat.
AB  - Central vasopressin (VP) release from magnocellular neuroendocrine cells (MNCs)
      in the supraoptic nucleus (SON) occurs from their somata and dendrites within the
      SON several hours after acute dehydration, and is an important autoregulatory
      mechanism influencing the systemic release of VP from MNC terminals in the
      posterior pituitary. To begin to explore the impact of polychlorinated biphenyls
      (PCBs) on brain mechanisms of body fluid regulation, both central and systemic VP
      release in response to acute dehydration were assessed in adult male rats fed the
      commercial PCB mixture Aroclor 1254 (30 mg/kg/day) for 15 days. Water intake and
      body weight were recorded daily, and on day 15 rats were dehydrated by
      intraperitoneal injection of 3.5 M saline (controls received physiological
      saline) and sacrificed 4-6 h later. Intranuclear VP release was measured in SON
      tissue punches in vitro, and systemic VP release was measured in the same rats.
      SON prepared from dehydrated PCB-naive rats released significantly more VP than
      did SON from control rats (4.9 +/- 0.8 vs. 2.7 +/- 0.4 pg/ml/microg). In
      contrast, while Aroclor 1254 exposure had no effect on baseline water intake,
      weight gain, or plasma osmolality responses to dehydration in PCB-fed rats, the
      SON failed to respond with increased VP release during dehydration. Consistent
      with previous studies showing an inhibitory effect of central VP on plasma VP
      output, dehydrated PCB-fed rats had an exaggerated 863% increase in plasma VP
      over basal levels, compared to a 241% increase in PCB-naive rats, suggesting that
      the MNC system is subtly disrupted.

PMID- 15574675
TI  - Stachybotrys chartarum alters surfactant-related phospholipid synthesis and
      CTP:cholinephosphate cytidylyltransferase activity in isolated fetal rat type II
      cells.
AB  - Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly
      grows on damp cellulose-containing materials. It produces a complex array of
      mycotoxins. Their mechanisms of action on the pulmonary system are not entirely
      clear. Previous studies suggest spore products may depress formation of
      disaturated phosphatidylcholine (DSPC), the major surface-active component of
      pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this
      phospholipid, then mold exposure may be a significant issue for pulmonary
      function in both mature lung and developing fetal lung. To address this
      possibility, fetal rat type II cells, the principal source of DSPC, were used to
      assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat
      lung type II cells prelabeled with 3H-choline and incubated with spore extract
      showed decreased incorporation of 3H-choline into DSPC. The activity of
      CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in
      phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution
      of spore extract. Two different S. chartarum extracts (isolates from S. chartarum
      (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in
      the presence of phosphatidylglycerol (PG), a known activator. PG produced an
      approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did
      not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced
      activation of CPCT. These results support previous observations that mold
      products alter PS metabolism and may pose a risk in developing lung, inhibiting
      surfactant synthesis. Different isolates of the same species of fungus are not
      equivalent in terms of potential exposure risks.

PMID- 15574676
TI  - It is time to move on.....

PMID- 15574677
TI  - TGF-beta signal transduction in oro-facial health and non-malignant disease (part
      I).
AB  - The transforming growth factor-beta (TGF-beta) family of cytokines consists of
      multi-functional polypeptides that regulate a variety of cell processes,
      including proliferation, differentiation, apoptosis, extracellular matrix
      elaboration, angiogenesis, and immune suppression, among others. In so doing, TGF
      beta plays a key role in the control of cell behavior in both health and disease.
      In this report, we review what is known about the mechanisms of activation of the
      peptide, together with details of TGF-beta signal transduction pathways. This
      review summarizes the evidence implicating TGF-beta in normal physiological
      processes of the craniofacial complex-such as palatogenesis, tooth formation,
      wound healing, and scarring-and then evaluates its role in non-malignant disease
      processes such as scleroderma, submucous fibrosis, periodontal disease, and
      lichen planus.

PMID- 15574678
TI  - The role of TGF-beta in epithelial malignancy and its relevance to the
      pathogenesis of oral cancer (part II).
AB  - The role of transforming growth factor-beta (TGF-beta) in epithelial malignancy
      is complex, but it is becoming clear that, in the early stages of carcinogenesis,
      the protein acts as a potent tumor suppressor, while later, TGF-beta can function
      to advance tumor progression. We review the evidence to show that the pro
      oncogenic functions of TGF-beta are associated with (1) a partial loss of
      response to the ligand, (2) defects of components of the TGF-beta signal
      transduction pathway, (3) over-expression and/or activation of the latent
      complex, (4) epithelial-mesenchymal transition, and (5) recruitment of signaling
      pathways which act in concert with TGF-beta to facilitate the metastatic
      phenotype. These changes are viewed in the context of what is known about the
      pathogenesis of oral cancer and whether this knowledge can be translated into the
      development of new therapeutic modalities.

PMID- 15574679
TI  - Pathogenesis of apical periodontitis and the causes of endodontic failures.
AB  - Apical periodontitis is a sequel to endodontic infection and manifests itself as
      the host defense response to microbial challenge emanating from the root canal
      system. It is viewed as a dynamic encounter between microbial factors and host
      defenses at the interface between infected radicular pulp and periodontal
      ligament that results in local inflammation, resorption of hard tissues,
      destruction of other periapical tissues, and eventual formation of various
      histopathological categories of apical periodontitis, commonly referred to as
      periapical lesions. The treatment of apical periodontitis, as a disease of root
      canal infection, consists of eradicating microbes or substantially reducing the
      microbial load from the root canal and preventing re-infection by orthograde root
      filling. The treatment has a remarkably high degree of success. Nevertheless,
      endodontic treatment can fail. Most failures occur when treatment procedures,
      mostly of a technical nature, have not reached a satisfactory standard for the
      control and elimination of infection. Even when the highest standards and the
      most careful procedures are followed, failures still occur. This is because there
      are root canal regions that cannot be cleaned and obturated with existing
      equipments, materials, and techniques, and thus, infection can persist. In very
      rare cases, there are also factors located within the inflamed periapical tissue
      that can interfere with post-treatment healing of the lesion. The data on the
      biological causes of endodontic failures are recent and scattered in various
      journals. This communication is meant to provide a comprehensive overview of the
      etio-pathogenesis of apical periodontitis and the causes of failed endodontic
      treatments that can be visualized in radiographs as asymptomatic post-treatment
      periapical radiolucencies.

PMID- 15574680
TI  - The use of enamel matrix derivative in the treatment of periodontal defects: a
      literature review and meta-analysis.
AB  - BACKGROUND: Periodontal disease results in the loss of the attachment apparatus.
      In the last three decades, an increasing effort has been placed on seeking
      procedures and materials to promote the regeneration of this tissue. The aim of
      this paper is to evaluate the effect of enamel matrix derivative (EMD) during
      regenerative procedures. In addition, a meta-analysis is presented regarding the
      clinical results during regeneration with EMD, to gain evidence as to what can be
      accomplished following treatment of intrabony defects with EMD in terms of
      probing depth reduction, clinical attachment level gain, defect fill (using re
      entry studies), and radiographic parameters. METHODS: The review includes in
      vitro and in vivo studies as well as human case reports, clinical comparative
      trials, and histologic findings. In addition, a meta-analysis is presented
      regarding the regenerative clinical results. For this purpose, we used 28 studies
      including 955 intrabony defects treated with EMD that presented baseline and
      final data on probing depth, clinical attachment level (CAL) gain, or bone gain
      to calculate weighted mean changes in the different parameters. The selected
      studies were pooled from the MEDLINE database at the end of May, 2003. RESULTS:
      The meta-analysis of intrabony defects treated with EMD resulted in a mean
      initial probing depth of 7.94 +/- 0.05 mm that was reduced to 3.63 +/- 0.04 mm (p
      = 0.000). The mean clinical attachment level changed from 9.4 +/- 0.06 mm to 5.82
      +/- 0.07 mm (p = 0.000). These results were significantly better than the results
      obtained for either open-flap debridement (OFD) or guided tissue regeneration
      (GTR). In contrast, histologically, GTR is more predictable than EMD in terms of
      bone and cementum formation. No advantage was found for combining EMD and GTR.
      Xenograft, or EMD and xenograft, yielded inferior results compared with EMD
      alone, but a limited number of studies evaluated this issue. Promising results
      were noted for the combination of allograft materials and EMD. CONCLUSIONS: EMD
      seems to be safe, was able to regenerate lost periodontal tissues in previously
      diseased sites based on clinical parameters, and was better than OFD or GTR. Its
      combination with allograft materials may be of additional benefit but still needs
      to be further investigated.

PMID- 15574681
TI  - Oral health, atherosclerosis, and cardiovascular disease.
AB  - During the last two decades, there has been an increasing interest in the impact
      of oral health on atherosclerosis and subsequent cardiovascular disease (CVD).
      The advent of the inflammation paradigm in coronary pathogenesis stimulated
      research in chronic infections caused by a variety of micro-organisms-such as
      Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus-as well as dental
      pathogens, since these chronic infections are thought to be involved in the
      etiopathogenesis of CVD by releasing cytokines and other pro-inflammatory
      mediators (e.g., C-reactive protein [CRP], tumor necrosis factor [TNF-alpha])
      that may initiate a cascade of biochemical reactions and cause endothelial damage
      and facilitate cholesterol plaque attachment. Yet, due to the multi-factorial
      nature of dental infection and CVD, confirming a causal association is difficult,
      and the published results are conflicting. The main deficit in the majority of
      these studies has been the inadequate control of numerous confounding factors,
      leading to an overestimation and the imprecise measurement of the predictor or
      overadjustment of the confounding variables, resulting in underestimation of the
      risks. A meta-analysis of prospective and retrospective follow-up studies has
      shown that periodontal disease may increase the risk of CVD by approximately 20%
      (95% confidence interval [CI], 1.08-1.32). Similarly, the reported risk ratio
      between periodontal disease and stroke is even stronger, varying from 2.85 (CI
      1.78-4.56) to 1.74 (CI 1.08-2.81). The association between peripheral vascular
      disease and oral health parameters has been explored in only two studies, and the
      resultant relative risks among individuals with periodontitis were 1.41 (CI 1.12
      1.77) and 2.27 (CI 1.32-3.90), respectively. Overall, it appears that periodontal
      disease may indeed contribute to the pathogenesis of cardiovascular disease,
      although the statistical effect size is small.

PMID- 15574683
TI  - Epidermal growth factor receptor-dependent and -independent pathways in hydrogen
      peroxide-induced mitogen-activated protein kinase activation in cardiomyocytes
      and heart fibroblasts.
AB  - Mild doses of oxidative stress in the heart correlate with the induction of
      apoptosis or hypertrophy in cardiomyocytes (CMCs) and fibrosis or proliferation
      of fibroblasts. Three branches of mitogen-activated protein kinases (MAPKs),
      i.e., c-Jun N-terminal kinases (JNKs), extracellular signal-related kinases 1 and
      2 (ERK1/2), and p38, are activated by oxidants in a variety of cell types,
      including CMCs. However, the initiation process of these signaling pathways
      remains unsolved. We explored the role of the epidermal growth factor (EGF)
      receptor in H(2)O(2)-induced MAPK activation using two different cell types from
      the same organ: CMCs and heart fibroblasts (HFs). Pretreatment of each cell type
      with EGF revealed differences in how CMCs and HFs responded to subsequent
      treatment with H(2)O(2): in CMCs, the second treatment resulted in little further
      activation of JNKs and ERK1/2, whereas HFs retained the full response of JNKs and
      ERK1/2 activation by H(2)O(2) regardless of EGF pretreatment. AG-1478 [4-(3'
      chloroanilino)-6,7-dimethoxy-quinazoline], a pharmacologic inhibitor of the EGF
      receptor tyrosine kinase, inhibited JNK and ERK1/2 activations but not p38 in
      both cell types. The data using the Src inhibitor PP2 [4-amino-5-(4-chlorophenyl)
      7-(t-butyl)pyrazolo[3,4-d]pyrimidine] resemble those found when using AG-1478 in
      either cell type. Pharmacologic inhibitors of matrix metalloproteinases (MMPs)
      further illustrated the difference between the two cell types. In HFs, MMP
      inhibitors GM6001 [N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-l
      tryptophan methylamide] and BB2516 [[2S-[N4(R(*)),2R(*),3S(*)]]-N4-[2,2-dimethyl
      1-[(methylamino)carbonyl]propyl]-N1,2-dihydroxy-3-(2-methylpropyl)butanediamide,
      marimastat] inhibited JNKs and ERK1/2 activation without affecting p38 activation
      by H(2)O(2) inhibitors. In contrast, these MMP failed to significantly inhibit
      the activation of JNKs, ERKs, or p38 in CMCs. These data suggest the complexity
      of the cell type-dependent signaling web initiated by oxidants in the heart.

PMID- 15574684
TI  - Evidence for pleiotropic signaling at the mouse beta3-adrenoceptor revealed by
      SR59230A [3-(2-Ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2
      propanol oxalate].
AB  - This study examines the action of the beta(3)-adrenoceptor antagonist SR59230A [3
      (2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2
      propanoloxalate] at cloned mouse beta(3)-adrenoceptors expressed in Chinese
      hamster ovary cells (CHO-K1-beta(3)) or endogenously expressed in 3T3-F442A
      adipocytes or ileum. SR59230A displayed partial agonist properties compared with
      the beta(3)-adrenoceptor agonist CL316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2
      hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate] in CHO-K1-beta(3)
      with the intrinsic activity increasing with the level of receptor expression.
      Functional affinity values for SR59230A at each level of receptor expression were
      in agreement with pK(I) values determined by binding. In cytosensor
      microphysiometer studies, SR59230A was a full agonist for increases in
      extracellular acidification rates (ECARs) at all levels of receptor expression,
      and antagonist actions were measurable only in medium- or low-expressing cells.
      In 3T3-F442A adipocytes, SR59230A antagonized CL316243-mediated increases of cAMP
      and had no agonist actions. However, in the cytosensor micro-physiometer,
      SR59230A (acting via beta(3)-adrenoceptors) was an agonist with an intrinsic
      activity greater than CL316243. In mouse ileum, SR59230A relaxed smooth muscle,
      although concentration-response curves were biphasic. Relaxant effects were
      produced by concentrations that did not affect cAMP levels. Differences in tissue
      responses to SR59230A were not caused by major differences in expression of
      Galphas. ECAR responses were not affected by pretreatment of cells with pertussis
      toxin, indicating that signaling did not involve Gi. Therefore, SR59230A displays
      agonist and antagonist actions at the mouse beta(3)-adrenoceptor. Because
      SR59230A only antagonized accumulation of cAMP in 3T3-F442A adipocytes yet in the
      same cells was an agonist for ECAR, cAMP-independent signaling pathways must
      mediate part of the agonist actions in the microphysiometer.

PMID- 15574685
TI  - Pharmacologic interactions between the muscarinic cholinergic and dopaminergic
      systems in the modulation of prepulse inhibition in rats.
AB  - Prepulse inhibition (PPI) of the acoustic startle reflex is a sensorimotor gating
      process known to be deficient in a number of neurologic and psychiatric
      conditions, including schizophrenia. Multiple lines of evidence have indicated
      that the dopaminergic and muscarinic cholinergic systems play an important role
      in modulating PPI. Moreover, interactions between the dopaminergic and muscarinic
      cholinergic systems are well known; however, little is known about potential
      interactions between the two systems in modulating PPI. Therefore, the purpose of
      the present studies was to determine whether interactions occur between the
      muscarinic cholinergic and dopaminergic systems in modulating PPI. The efficacy
      of muscarinic cholinergic receptor agonists in reversing the disruption of PPI
      induced by apomorphine, a D1/D2 dopamine receptor agonist, was evaluated in male
      Sprague-Dawley rats. The M1/M4-preferring muscarinic agonist xanomeline and the
      M2/M4-preferring agonist BuTAC [([5R-[exo]-6-[butylthio]-1,2,5-thiadiazol-3-yl-]
      1-azabyciclo-[3.2.1])octane oxalate] reversed the apomorphine-induced disruption
      of PPI in a manner similar to that produced by the D2-like dopamine receptor
      antagonists haloperidol and olanzapine. The muscarinic agonists oxotremorine,
      RS86 [[2-ethyl-8-methyl-2,8-diazaspiro(4.5)decane-1,3-dione] hydrochloride],
      pilocarpine, milameline, and sabcomeline also reversed the apomorphine-induced
      disruption of PPI. Moreover, the muscarinic antagonist scopolamine also disrupted
      PPI, and the D2-like receptor antagonist haloperidol, but not the D1-like
      receptor antagonist SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine], reversed the scopolamine-induced disruption. In
      addition, xanomeline produced a significant reversal of the disruption in PPI
      produced by scopolamine. Collectively, the present findings demonstrate that a
      functional interaction occurs between the muscarinic cholinergic and dopaminergic
      systems in modulating PPI and that muscarinic cholinergic agonists may be
      effective in the treatment of the PPI and other cognitive impairments observed in
      schizophrenia.

PMID- 15574686
TI  - Repeated cocaine administration increases membrane excitability of pyramidal
      neurons in the rat medial prefrontal cortex.
AB  - Although the medial prefrontal cortex (mPFC) plays a critical role in cocaine
      addiction, the effects of chronic cocaine on mPFC neurons remain poorly
      understood. Here, we performed visualized current-clamp recordings to determine
      the effects of repeated cocaine administration on the membrane excitability of
      mPFC pyramidal neurons in rat brain slices. Following repeated cocaine
      administration (15 mg/kg/day i.p. for 5 days) with a 3-day withdrawal,
      alterations in membrane properties, including increased input resistance, reduced
      intensity of intracellular injected currents required for generation of Na(+)
      dependent spikes (rheobase), and an increased number of spikes evoked by
      depolarizing current pulses were observed in mPFC neurons. The current-voltage
      relationship was also altered in cocaine-pretreated neurons showing reduced
      outward rectification during membrane depolarization and decreased inward
      rectification during membrane hyperpolarization. Application of the K(+) channel
      blocker Ba(2+) depolarized the resting membrane potential (RMP) and enhanced
      membrane potential response to injection of hyperpolarizing current pulses.
      However, the effects of Ba(2+) on RMP and hyperpolarized membrane potentials were
      significantly attenuated in cocaine-withdrawn neurons compared with saline
      pretreated cells. These findings indicate that repeated cocaine administration
      increased the excitability of mPFC neurons after a short-term withdrawal,
      possibly via reducing the activity of the potassium inward rectifiers (K(ir)) and
      voltage-gated K(+) currents. Similar changes were also observed in cocaine
      pretreated mPFC neurons after a long-term (2-3 weeks) withdrawal, revealing a
      persistent increase in excitability. These alterations in mPFC neuronal
      excitability may contribute to the development of behavioral sensitization and
      withdrawal effects following chronic cocaine exposure.

PMID- 15574688
TI  - Choosing a doctoral program in nursing: what to consider.

PMID- 15574687
TI  - Comparison of peptidic and nonpeptidic delta-opioid agonists on guanosine 5'-O-(3
      [35S]thio)triphosphate ([35S]GTPgammaS) binding in brain slices from Sprague
      Dawley rats.
AB  - Previous studies have demonstrated that peptidic and nonpeptidic delta-opioid
      receptor agonists have different effects depending on the measure. For example,
      nonpeptidic delta-opioid agonists, but not peptidic agonists, produce convulsions
      in rats, and in vitro studies suggested that peptidic and nonpeptidic delta
      opioid agonists might have differential mechanisms of receptor downregulation.
      The present study evaluated potential differences between peptidic and
      nonpeptidic delta-opioid agonists in their ability to activate G proteins using
      guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) autoradiography
      experiments in rat brain slices. The peptidic agonist [d-Pen(2),d-Pen(5)]
      enkephalin and the nonpeptidic agonist (+)BW373U86 [(+)-4-[alpha(R)-alpha
      [(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N
      diethylbenzamide] demonstrated concentration-dependent increases in
      [(35)S]GTPgammaS binding that were attenuated by the delta-opioid antagonist
      naltrindole. (+)BW373U86 was more potent and efficacious than the peptidic
      agonist, and this difference remained consistent across brain regions where
      significant stimulation was observed. In addition, multiple delta-opioid
      compounds were evaluated for their agonist activity in this assay. These data
      suggested that differences between peptidic and nonpeptidic delta-opioid agonists
      in behavioral studies were most likely caused by differences in agonist efficacy.
      Finally, these data also revealed that [(35)S]GTPgammaS autoradiography could be
      used to compare efficacy differences among agonists across various brain regions
      in rat brain slices.

PMID- 15574689
TI  - Feeling lonely: theoretical perspectives.
AB  - Much has been written about the phenomenon of loneliness. Despite the plethora of
      theoretical information concerning loneliness, the phenomenon lacks a clear,
      consensual definition. Nurses often work with persons who feel lonely. Feeling
      lonely is a phenomenon that is a universal lived experience that is significant
      to health and quality of life. In this column, the author examines the existing
      body of theoretical knowledge regarding the phenomenon of feeling lonely. The
      author's perspective is the human becoming theory, in which health is viewed as
      the way individuals live what is important to them.

PMID- 15574691
TI  - Directions for doctoral dissertation research.

PMID- 15574692
TI  - The ethics of respect in nursing.
AB  - The term respect is pervasive in biomedical ethical literature and in all
      disciplines. It is a concept used to connote dignity, reverence, and regard. To
      demonstrate respect implies actions of doing what is good. When viewed in the
      context of nursing research, practice, and education, questions abound as to how
      respect is offered to others. The author of this column examines and offers
      possible definitions for the term respect and provides possible implications for
      leadership in nursing from a nursing theoretical perspective.

PMID- 15574693
TI  - Becoming a living-learning organization.
AB  - The journey of becoming a living-learning organization brings forth many
      challenges while relating with community. Parse's nursing theory of human
      becoming provides a framework for understanding meaning, rhythmicity, and
      cotranscendence while relating with others. In this column the authors discuss
      how the theory of human becoming and the key components of a learning
      organization informed the cocreation of a shared vision for Sioux Valley
      Hospitals and Health System. Parse's community change concepts, moving
      initiating, anchoring-shifting, pondering-shaping, are intertwined within story
      as discovery, intention, innovation, and fostering human potential in this
      organizational change process is explored.

PMID- 15574694
TI  - Practice possibilities for nurses choosing true presence with persons who live
      with a different sense of hearing.
AB  - Living with a different sense of hearing is a silencing experience that can
      change persons'patterns of relating and even deprive them of effective ways to
      give and receive messages with other human beings. People who live with having a
      different sense of hearing are often stigmatized, labeled, and judged by nurses,
      healthcare professionals, and family members alike. This column examines practice
      possibilities for nurses who choose the human becoming way of being with persons
      living with a different sense of hearing.

PMID- 15574695
TI  - Advanced practice nursing: continuation of the dialogue.
AB  - This column continues the dialogue about advanced practice nursing. Professor
      Iain Graham of Bournemouth University shares his ideas about advanced practice
      nursing in the United Kingdom and answers questions about the tasks and
      responsibilities of advanced practice nurses within the National Health Service.

PMID- 15574696
TI  - The well-being picture scale: a revision of the index of field energy.
AB  - This paper reports the development and psychometric properties of the Well-Being
      Picture Scale, a 10-item non-language based pictorial scale that measures general
      well-being, based on Martha Rogers'view of human beings as energy fields in
      continual mutual process with their environment. The Well-Being Picture Scale was
      designed for use with the broadest possible range of adult populations, including
      persons who are unable to respond to English-based text or lengthy, complex
      measurement instruments. Psychometric properties were established in a sample of
      more than 2,000 individuals from the United States, Taiwan, Japan, and Africa.
      The overall Cronbach's alpha is .8795.

PMID- 15574697
TI  - Being a sibling.
AB  - The purpose of this descriptive exploratory study was to explore the meaning of
      being a sibling using Parse's human becoming perspective. Twelve children between
      5 and 15 years of age with a younger sibling with a cleft lip and palate or Down
      Syndrome participated. Through semi-structured interviews and the use of art,
      children talked about their experiences. Major themes portrayed the complex and
      paradoxical nature of being a sibling. The themes also revealed that having a
      sibling with special circumstances includes some unique opportunities and
      challenges. The finding of this study is the descriptive statement, being a
      sibling is an arduous charge to champion close others amid restricting-enhancing
      commitments while new endeavors give rise to new possibilities. Implications for
      nursing are discussed in the context of understanding being a sibling.

PMID- 15574698
TI  - Children's experiences of being without a place to call home: what the research
      tells us.
AB  - The article provides a critique of qualitative nursing research regarding
      children's experiences of being without a place to call home. The phenomena under
      study were the lived experience of being without a home, feeling uncomfortable,
      hope, and what was special in the children's lives. Parse's criteria for the
      critique of qualitative research were used. A synthesis of the interpretive
      findings about the children's experiences is presented. Recommendations for
      advancing nursing theory, nursing research, and nursing practice are discussed.

PMID- 15574699
TI  - Self-care for stoma surgery: mastering independent stoma self-care skills in an
      elderly woman.
AB  - According to Orem, active participation in caring for self contributes to the
      behavior of self-care. Before an individual is able to care for oneself, however,
      many factors must be considered. This article is based on an alert, oriented 85
      year old widow, known as EL, who was recently diagnosed with rectal cancer. With
      postoperative hypertension and sinus tachycardia, EL is having difficulty
      learning self-care. This article demonstrates a scenario where Orem's self-care
      deficit theory of nursing assisted in developing an effective plan of self-care
      for an elderly woman who underwent an ileostomy.

PMID- 15574700
TI  - Blame it on Rio?

PMID- 15574701
TI  - Challenges in coming of age in Korea.
AB  - Nurses in the field of addictions and substance abuse have assumed, along with
      most of medicine, that alcohol abuse is a multifactoral health problem. The
      narratives of two college student's comments about their experiences of excessive
      drinking are considered from the human becoming theory as an alternative
      perspective to the causal theories which are dominant in the addictions and
      substance abuse fields. These issues are also considered from a human becoming
      perspective.

PMID- 15574702
TI  - The phenomenological movement and research in the human sciences.
AB  - Phenomenology, as a modern movement in philosophy, has focused discussion upon
      human subjectivity in new and critically important ways. Because human
      participants can relate intentionally to objects of the world consciousness
      manifests relationships to things and others that are other than cause-effect
      relationships. Consequently, the concepts and practices of the natural sciences
      are not the best model for the human sciences to follow. Husserl in his
      philosophy introduced a method for a more adequate approach to the achievements
      of consciousness and when properly modified the phenomenological method can serve
      as the basis for the human sciences, including nursing. The use of such a method
      can make the qualitative analysis of phenomena rigorous and scientific.

PMID- 15574704
TI  - Amyloidogenic self-assembly of insulin aggregates probed by high resolution
      atomic force microscopy.
AB  - As the application of high-resolution atomic force microscopy (AFM) has led us
      recently to the discovery of a unique pressure-induced circular amyloid, we used
      the same approach to examine morphological events accompanying insulin
      aggregation under ambient conditions. This study presents the multistage,
      hierarchical character of the spontaneous fibrillation of insulin at low pH and
      at 60 and 70 degrees C, and-due to the marked enhancement of image resolution
      achieved-brings new clues as to the fibrils' ultrastructure and mechanisms of its
      assembly. Specifically, focusing on the prefibrillar amorphous aggregates
      occurring 30 s after elevating temperature to the nucleation-enhancing 60 degrees
      C, revealed the tendency of the globule-shaped oligomers to queue and assembly
      into elongated forms. This suggests that the shape of the nuclei itself
      predetermines-in part-the fibrillar architecture of the amyloid. Among first
      fibrillar features, short but relatively thick (8-nm) seedlike forms appeared on
      a very short timescale within the first minute of incubation. It has been shown
      that such fibrils are likely to act as lateral scaffolds for the growth of
      amyloid. By using phase-image AFM as a nanometer-resolved probe of visco-elastic
      surface properties, we were able to show that bundles of early protofilaments
      associated into parallel fibrils are capable of a cooperative transformation into
      twisted, highly ordered superhelices of the mature amyloid. Independently from
      producing evidence for the step-resolved character of the process, intermediate
      and morphologically heterogeneous forms were trapped and characterized, which
      yields direct evidence for the multipathway character of the amyloidogenesis of
      insulin. Apart from the faster kinetics, the increased temperature of 70 degrees
      C leads to a higher degree of morphological variability: along straight rods,
      twisted ribbonlike structures, rod bundles, and ropelike structures become
      prominent in the corresponding AFM data.

PMID- 15574705
TI  - Properties of metabolic networks: structure versus function.
AB  - Biological data from high-throughput technologies describing the network
      components (genes, proteins, metabolites) and their associated interactions have
      driven the reconstruction and study of structural (topological) properties of
      large-scale biological networks. In this article, we address the relation of the
      functional and structural properties by using extensively experimentally
      validated genome-scale metabolic network models to compute observable functional
      states of a microorganism and compare the "structure versus function" attributes
      of metabolic networks. It is observed that, functionally speaking, the
      essentiality of reactions in a node is not correlated with node connectivity as
      structural analyses of other biological networks have suggested. These findings
      are illustrated with the analysis of the genome-scale biochemical networks of
      three species with distinct modes of metabolism. These results also suggest
      fundamental differences among different biological networks arising out of their
      representation and functional constraints.

PMID- 15574706
TI  - Homology modeling and molecular dynamics simulations of transmembrane domain
      structure of human neuronal nicotinic acetylcholine receptor.
AB  - A three-dimensional model of the transmembrane domain of a neuronal-type
      nicotinic acetylcholine receptor (nAChR), (alpha4)2(beta2)3, was constructed from
      a homology structure of the muscle-type nAChR recently determined by cryo
      electron microscopy. The neuronal channel model was embedded in a fully hydrated
      DMPC lipid bilayer, and molecular-dynamics simulations were performed for 5 ns. A
      comparative analysis of the neuronal- versus muscle-type nAChR models revealed
      many conserved pore-lining residues, but an important difference was found near
      the periplasmic mouth of the pore. A flickering salt-bridge of alpha4-E266 with
      its adjacent beta2-K260 was observed in the neuronal-type channel during the
      course of the molecular-dynamics simulations. The narrowest region, with a pore
      radius of approximately 2 A formed by the salt-bridges, does not seem to be the
      restriction site for a continuous water passage. Instead, two hydrophobic rings,
      formed by alpha4-V259, alpha4-L263, and the homologous residues in the beta2
      subunits, act as the gates for water flow, even though the region has a slightly
      larger pore radius. The model offers new insight into the water transport across
      the (alpha4)2(beta2)3 nAChR channel, and may lead to a better understanding of
      the structures, dynamics, and functions of this family of ion channels.

PMID- 15574707
TI  - Distribution, lateral mobility and function of membrane proteins incorporated
      into giant unilamellar vesicles.
AB  - GUVs have been widely used for studies on lipid mobility, membrane dynamics and
      lipid domain (raft) formation, using single molecule techniques like fluorescence
      correlation spectroscopy. Reports on membrane protein dynamics in these types of
      model membranes are by far less advanced due to the difficulty of incorporating
      proteins into GUVs in a functional state. We have used sucrose to prevent four
      distinct membrane protein(s) (complexes) from inactivating during the dehydration
      step of the GUV-formation process. The amount of sucrose was optimized such that
      the proteins retained 100% biological activity, and many proteo-GUVs were
      obtained. Although GUVs could be formed by hydration of lipid mixtures composed
      of neutral and anionic lipids, an alternate current electric field was required
      for GUV formation from neutral lipids. Distribution, lateral mobility, and
      function of an ATP-binding cassette transport system, an ion-linked transporter,
      and a mechanosensitive channel in GUVs were determined by confocal imaging,
      fluorescence correlation spectroscopy, patch-clamp measurements, and biochemical
      techniques. In addition, we show that sucrose slows down the lateral mobility of
      fluorescent lipid analogs, possibly due to hydrogen-bonding with the lipid
      headgroups, leading to larger complexes with reduced mobility.

PMID- 15574708
TI  - Molecular force modulation spectroscopy revealing the dynamic response of single
      bacteriorhodopsins.
AB  - Recent advances in atomic force microscopy allowed globular and membrane proteins
      to be mechanically unfolded on a single-molecule level. Presented is an extension
      to the existing force spectroscopy experiments. While unfolding single
      bacteriorhodopsins from native purple membranes, small oscillation amplitudes (6
      9 nm) were supplied to the vertical displacement of the cantilever at a frequency
      of 3 kHz. The phase and amplitude response of the cantilever-protein system was
      converted to reveal the elastic (conservative) and viscous (dissipative)
      contributions to the unfolding process. The elastic response (stiffness) of the
      extended parts of the protein were in the range of a few tens pN/nm and could be
      well described by the derivative of the wormlike chain model. Discrete events in
      the viscous response coincided with the unfolding of single secondary structure
      elements and were in the range of 1 microNs/m. In addition, these force
      modulation spectroscopy experiments revealed novel mechanical unfolding
      intermediates of bacteriorhodopsin. We found that kinks result in a loss of
      unfolding cooperativity in transmembrane helices. Reconstructing force-distance
      spectra by the integration of amplitude-distance spectra verified their position,
      offering a novel approach to detect intermediates during the forced unfolding of
      single proteins.

PMID- 15574709
TI  - Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces.
      III. Numerical simulation of tethering under flow.
AB  - Transient capture of cells or model microspheres from flow over substrates
      sparsely coated with adhesive ligands has provided significant insight into the
      unbinding kinetics of leukocyte:endothelium adhesion complexes under external
      force. Whenever a cell is stopped by a point attachment, the full hydrodynamic
      load is applied to the adhesion site within an exceptionally short time-less than
      the reciprocal of the hydrodynamic shear rate (e.g., typically <0.01 s). The
      decay in numbers of cells or beads that remain attached to a surface has been
      used as a measure of the kinetics of molecular bond dissociation under constant
      force, revealing a modest increase in detachment rate at growing applied shear
      stresses. On the other hand, when detached under steady ramps of force with
      mechanical probes (e.g., the atomic force microscope and biomembrane force
      probe), P-selectin:PSGL-1 adhesion bonds break at rates that increase enormously
      under rising force, yielding 100-fold faster off rates at force levels comparable
      to high shear. The comparatively weak effect of force on tether survival in flow
      chamber experiments could be explained by a possible partition of the load
      amongst several bonds. However, a comprehensive understanding of the difference
      in kinetic behavior requires us to also inspect other factors affecting the
      dynamics of attachment-force buildup, such as the interfacial compliance of all
      linkages supporting the adhesion complex. Here, combining the mechanical
      properties of the leukocyte interface measured in probe tests with single-bond
      kinetics and the kinetics of cytoskeletal dissociation, we show that for the
      leukocyte adhesion complex P-selectin:PSGL-1, a detailed adhesive dynamics
      simulation accurately reproduces the tethering behavior of cells observed in flow
      chambers. Surprisingly, a mixture of 10% single bonds and 90% dimeric bonds is
      sufficient to fully match the data of the P-selectin:PSGL-1 experiments, with the
      calculated decay in fraction of attached cells still appearing exponential.

PMID- 15574710
TI  - Effects of monofunctional adducts of platinum(II) complexes on thermodynamic
      stability and energetics of DNA duplexes.
AB  - Effects of adducts of [PtCl(NH3)3]Cl or chlorodiethylenetriamineplatinum(II) on
      DNA stability were studied with emphasis on thermodynamic origins of that
      stability. Oligodeoxyribonucleotide duplexes (15-bp) containing the single, site
      specific monofunctional adduct at G-residues of the central sequences TGT/ACA or
      5'-AGT/5'-ACT were prepared and analyzed by differential scanning calorimetry,
      temperature-dependent ultraviolet absorption and circular dichroism. The
      unfolding of the platinated duplexes was accompanied by relatively small
      unfavorable free energy terms. This destabilization was enthalpic in origin. On
      the other hand, a relatively large reduction of melting temperature (T(m)) was
      observed as a consequence of the monofunctional adduct in the TGT sequence,
      whereas T(m) due to the adduct in the AGT sequence was reduced only slightly. We
      also examined the efficiency of the mammalian nucleotide excision repair system
      to remove from DNA the monofunctional adducts and found that these lesions were
      not recognized by this repair system. Thus, rather thermodynamic than thermal
      characterization of DNA adducts of monofunctional platinum compounds is a
      property implicated in the modulation of downstream effects such as protein
      recognition and repair.

PMID- 15574711
TI  - Beyond the clinical trial: expanding criteria for evidence.

PMID- 15574712
TI  - The meaning of death as experienced by elderly women of a Korean clan.
AB  - The objective of this ethnography is to describe the meaning of death as
      experienced by the elderly. The authors collected data through participant
      observation and ethnographic interview with 14 key informants in a Korean clan
      between September 1994 and November 2001. They examined the data using taxonomy,
      proxemics, and value analysis techniques. Meanings of death included the end of
      pain, the dispersion of existence, moving to the next life by transcending the
      boundary, returning to the original place, and escalating into the world of the
      men's group. These meaning are constructed in a sociocultural context of research
      fields and in accordance with patterns of behavior in everyday life.

PMID- 15574713
TI  - Telephone social support or nursing presence? Analysis of a nursing intervention.
AB  - The purpose of this qualitative analysis is to elucidate more fully telephone
      social support as it was delivered within the context of a randomized controlled
      investigation. To this end, the author used constant comparative methods to
      analyze telephone logs. The findings are congruent with the operational
      definition of social support that was selected for the randomized controlled
      study; however, they are also suggestive of nursing presence. Components of
      nursing presence that emerged from the data include (a) maintenance of
      psychological presence, (b) interpersonal reciprocity characterized by a mutual
      desire to work together, (c) therapeutic communication and full attention to the
      here and now, and (d) expert nursing practice within the nurse-patient dyad.
      Outcomes include problem solving, adaptive behavior change, and diminished
      distress. Researchers are encouraged to continue to use qualitative methods to
      define and differentiate the concepts of social support and nursing presence more
      clearly. This is particularly important as the demand for empirically based
      nursing interventions grows.

PMID- 15574714
TI  - Victims twice over: perceptions and experiences of injured workers.
AB  - The authors discuss the qualitative component of a participatory research project
      conducted in Toronto, Ontario, between 1999 and 2001. Injured workers, who were
      trained as peer researchers, conducted one-time, semistructured interviews with
      other injured workers (N = 17) and helped with inductive coding and analyzing the
      interview transcripts. The qualitative research group consisted of seven peer
      researchers, four academic researchers, and a community legal worker. The group
      recruited interviewees by advertising on bulletin boards and in newsletters and
      newspapers, and selected a diverse group of interviewees who had encountered
      problems with the return-to-work process. Interviewees believed that the process
      victimizes them and renders them powerless and dependent on others. Furthermore,
      they considered that health professionals and bureaucrats impede their
      rehabilitation. The authors suggest that injured workers should be included in
      the decision-making process of rehabilitation and rebuilding their lives.

PMID- 15574715
TI  - Developing resilience: how women maintain their health in northern geographically
      isolated settings.
AB  - The purpose of this study was to explore how women maintain their health in
      northern geographically isolated settings, using a feminist grounded theory
      method. Twenty-five women of diverse backgrounds in northern British Columbia,
      Canada, engaged in qualitative interviews over a 2-year period to express
      perspectives about how the north affects their health and how they maintain their
      health in northern settings. Findings reveal that the women experienced
      vulnerability to physical health and safety risks, psychosocial health risks, and
      risks of inadequate health care. The women responded to these vulnerabilities by
      developing resilience through the strategies of becoming hardy, making the best
      of the north, and supplementing the north. These strategies, which reflect both
      individual and collective actions, were determined by the needs and interests of
      the women and their social and personal resources. The findings have implications
      for women's health research and health practices and policies in geographically
      isolated settings.

PMID- 15574716
TI  - Gestational diabetes: the meaning of an at-risk pregnancy.
AB  - Being diagnosed with gestational diabetes (GDM) is coupled with the implication
      that the woman and her fetus are at risk. In this study, the authors use a
      hermeneutic phenomenological approach to gain an in-depth understanding of GDM as
      pregnant women meaningfully experience it. They conducted conversational
      interviews with 12 women who were diagnosed with and being treated for diabetes
      in pregnancy. Data analysis involved a reflective process consistent with the
      guidelines of thematic analysis. Four themes identified as characteristic of the
      women's pregnancy experience were Living a Controlled Pregnancy, Balancing, Being
      a Responsible Mother, and Being Transformed. The findings challenge health care
      professionals to discuss openly and reassess their present models of care for
      pregnant women and their families.

PMID- 15574717
TI  - Chinese Canadian beliefs toward organ donation.
AB  - The authors' purpose in this study is to explore the values and beliefs regarding
      organ donation of Chinese Canadians. Data collection involved individual
      interviews (n = 15) and focus groups. The major organizing categories were the
      importance of context, and values and beliefs. The context included little
      knowledge about donation and possible influence of spiritual or cultural values.
      Lack of communication and the need to preserve an intact body were themes that
      emerged in relation to death and dying. In relation to organ donation, most
      participants thought it was "a noble deed," but fears about organ donation were
      similar to those reported in other studies. It is important to note the
      considerable diversity in beliefs among these participants.

PMID- 15574718
TI  - Quality-of-life concerns of African American breast cancer survivors within rural
      North Carolina: blending the techniques of photovoice and grounded theory.
AB  - Social norms imposing a prevailing silence around breast cancer in rural African
      American communities have made it difficult for survivors to express their
      quality-of-life (QOL) concerns. In this article, the authors describe how they
      blended the photovoice method (providing participants with cameras so they can
      record, discuss, and relate the realities of their lives) with grounded theory
      techniques to assist 13 African American breast cancer survivors from rural
      eastern North Carolina in (a) exploring how they perceive and address their QOL
      within their own social context and (b) developing a conceptual framework of
      survivorship QOL. The framework that emerged reveals that three social forces
      (racism, stigmas regarding cancer, and cultural expectations of African American
      women) drive four QOL concerns (seeking safe sources of support, adjusting to the
      role of cancer survivor, feeling comfortable about the future, and serving as
      role models) and that survivors address these concerns by relying on spiritual
      faith and devising strategies to maintain social standing.

PMID- 15574719
TI  - A letter of consequence: referral letters from general practitioners to secondary
      mental health services.
AB  - The referral letter is a key instrument in moving patients from primary to
      secondary care services. Consequently, the circumstances in which a referral
      should be made and its contents have been the subject of clinical guidelines.
      This article is based on a project that demonstrated that physicians do not
      adhere to clinical guidelines when referring patients to secondary mental health
      services. This research supports earlier findings into noncompliance with
      guidelines by general practitioners (GPs). The authors briefly note possible
      reasons, which have been the subject of some debate. They also present a content
      analysis of referral letters to demonstrate the important ways in which they
      differ from guideline criteria. However, their central argument is that the role
      of the referral letter in relation to the GP's repertoire of treatments has not
      been understood fully. Such understanding implies the need for a reexamination of
      the support available for GPs.

PMID- 15574720
TI  - Using critical ethnography to explore issues in health promotion.
AB  - In this article, the author outlines the need for a critical research method in
      the field of health promotion to explore the determinants of health. These
      determinants, including healthy child development, employment and working
      conditions, and education, for example, underlie many of the health issues that
      individuals experience. They are, in turn, influenced by nebulous factors such as
      patterns of inequality, and cultural norms, which are difficult to research using
      conventional methodologies. The author provides an overview of critical
      ethnography as a method for health promotion research. She describes specific
      data collection and analysis techniques, with the addition of critical discourse
      analysis to add scope to ethnographic findings. She concludes with an overview of
      the congruence between critical ethnography and health promotion research,
      including a discussion of the differences between critical ethnography and
      participatory action research.

PMID- 15574721
TI  - Demystifying the writing process.

PMID- 15574722
TI  - Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus
      syndrome.
AB  - Opsoclonus-myoclonus syndrome (OMS) is a rare, autoimmune neurological disorder
      that is poorly recognized and undertreated. Neuroblastoma is found in one half of
      the cases. Because of the high incidence of spontaneous regression of
      neuroblastoma, it is unknown whether not finding a tumor means there was none. To
      define demographic trends and the standard of care in the first large series of
      OMS, 105 children were recruited over a 13-year period in a retrospective
      questionnaire survey. Children with and without a tumor differed little in viral
      like prodrome and neurological symptoms. Earliest neurological symptoms were
      staggering and falling, leading to a misdiagnosis of acute cerebellitis. Later
      symptoms included body jerks, drooling, refusal to walk or sit, speech problems,
      decreased muscle tone, opsoclonus, and inability to sleep. Tumor resection alone
      did not provide adequate therapy for most. Adrenocorticotropic hormone (ACTH),
      prednisone, and intravenous immunoglobulin were used with equal frequency, but
      ACTH was associated with the best early response. More than one half of the
      children had relapses. Residual behavioral, language, and cognitive problems
      occurred in the majority. The delay in diagnosis (11 weeks) and initiation of
      treatment (17 weeks) is unacceptably long.

PMID- 15574723
TI  - Chemotherapy error reduction: a multidisciplinary approach to create templated
      order sets.
AB  - More than 48,000 newly diagnosed cancer patients can expect to have some adverse
      events related to their care each year. Historically, 20% of these adverse events
      have been medication related, and two thirds have been thought to be preventable.
      Since the majority of these errors occurred during the order writing process, the
      prioritized changes made at the joint pediatric program for Children's Hospital,
      Boston, and Dana-Farber Cancer Institute have been the initiation of templated
      orders and the development of a computerized order entry system. The goal of this
      initiative was to decrease errors related to chemotherapy administration by
      creating legible, complete, clearly defined order sets, and at the same time, to
      make order writing and reviewing more efficient. Chemotherapy templates were
      created using a consistent format and a rigorous multidisciplinary review
      process. Each order set includes the following: identification of the patient and
      cycle of chemotherapy to be given, criteria necessary to receive chemotherapy,
      chemotherapy orders with modifications if appropriate, and supportive care
      orders. Templated order sets have reduced the duplication of work efforts by
      significantly reducing the number of changes made during the order verification
      process; orders are more complete, and standardization has occurred.

PMID- 15574724
TI  - Outpatient chemotherapy administration: decreasing wait times for patients and
      families.
AB  - Increasingly, there is a trend to deliver chemotherapy, where possible, in the
      outpatient ambulatory setting. In the few studies that have explored the setting
      of cancer care, long wait times are frequently linked to dissatisfaction. Several
      factors contribute to lengthy waiting times for patients and their families: long
      registration processes, lag times associated with obtaining laboratory results,
      time required for patient assessments and preparation of chemotherapeutic agents,
      adequacy of nursing resources, and physical space constraints in relation to
      patient volumes. With the goal of improving care delivery in the outpatient
      clinic, a fast-tracking system was established. Program planning included
      establishing patient eligibility criteria, protocol and treatment
      appropriateness, interdepartmental collaboration, development of a communication
      plan for families and staff, negotiation of physical space, and allocation of
      human resources. This was instituted by re-allocating existing resources and
      establishing an autonomous nurse-managed chemotherapy clinic. This fast-tracking
      program has enabled us to use our existing resources with greater efficiency and
      improve patient care from safety and quality-of-life perspectives for those
      included in the program.

PMID- 15574725
TI  - Cardiovascular late effects.
AB  - This integrative literature review focuses on (1) the spectrum of cardiovascular
      late effects; (2) the factors that can influence the development of
      cardiovascular late effects; and (3) the role of the pediatric oncology nurse in
      minimizing the risks of cardiovascular late effects and associated disabilities
      in childhood cancer survivorship. The results showed that survivors who have been
      treated with radiation therapy, especially when the field includes the heart or
      the hypothalamic-pituitary axis (HPA), and specific chemotherapies are at
      increased risk for developing particular cardiovascular risk factors and/or
      cardiovascular disease. Younger age at diagnosis, longer time since treatment,
      and family history of early heart disease can further heighten the risks. The
      role of pediatric oncology nurses in the promotion of cardiovascular health for
      children with cancer across the illness trajectory is discussed.

PMID- 15574726
TI  - Parents' refusal of medical treatment for cultural or religious beliefs: an
      ethnographic study of health care professionals' experiences.
AB  - Pediatric nurses working in acute care settings serving religious and culturally
      diverse families may encounter parents whose beliefs influence treatment
      decisions. Previous literature describes how these complex situations lead to
      emotional distress and strained relationships between health care provider and
      family members. An ethnographic study was conducted to investigate the impact of
      parental treatment refusal on the bedside interactions between pediatric nurses
      and parents. Twenty in-depth interviews with nurses were conducted, and extensive
      field notes were taken during data collection. Emotional feelings associated with
      possible loss of guardianship and subsequent mandated treatment, the impact of
      the situation on the nurses' health and stress levels, and functional status were
      all explored. Three themes were identified following interpretive narrative
      analysis of transcriptions and field notes: weathering the storm of moral
      conflict, closeness and involvement versus distance and retreat, and battles
      between the supportive and oppositional groups. The findings of the study lead to
      a deeper understanding of the complexities of the ethical dilemma surrounding
      treatment refusal in pediatrics.

PMID- 15574727
TI  - A survey of pediatric oncology nurses' perceptions of parent educational needs.
AB  - Educating parents of children with cancer is a primary nursing responsibility in
      pediatric oncology. A survey using Delphi techniques was conducted with nurses
      attending a Children's Oncology Group Nursing Workshop to identify priority
      educational topics from pediatric oncology nurses' perspective. In round 1 of the
      survey, nurses were asked to identify 5 priority educational topics and 5 topics
      they spend the most time teaching parents. Twenty-four educational categories
      were identified by 199 nurses, and responses were sorted by category and
      frequencies tabulated. Information about treatment was the most frequently cited
      priority. Bone marrow suppression (BMS) was the second most important priority
      and was the topic nurses spent most time in teaching. Round 2 of the survey was
      sent via e-mail to 132 consenting participants from round 1. Nurses were asked to
      rate the importance of the categories from round 1 (presented in random order)
      during 4 time periods (diagnosis, initial treatment, maintenance, and off
      therapy). Nurses reported different teaching priorities across the continuum of
      treatment. Of note, teaching about end-of-life issues and alternative therapy
      were ranked as low in importance across all time points. These findings can be
      used to inform educational programs and materials development for parents of
      children with cancer.

PMID- 15574728
TI  - The effects of tonic locus ceruleus output on sensory-evoked responses of ventral
      posterior medial thalamic and barrel field cortical neurons in the awake rat.
AB  - In mammals, the pontine nucleus locus ceruleus (LC) is the sole source of
      norepinephrine (NE) projections to the forebrain. Increasing tonic discharge of
      LC neurons elevates extracellular levels of NE in the cortex and thalamus. Tonic
      LC discharge is linked to the level of wakefulness and behavioral performance,
      demonstrating an optimal firing rate during sustained attention tasks.
      Iontophoretic application of NE to target neurons in the forebrain has been shown
      to produce a diverse set of neuromodulatory actions, including augmentation of
      synaptically evoked discharge as well as suppression of spontaneous and stimulus
      evoked firing patterns. Iontophoretic studies cataloged potential NE effects;
      however, the context in which such actions could occur in awake behaving animals
      remained controversial. To address this issue, the current study examined the
      effects of increasing tonic LC output on spontaneous and stimulus-evoked
      discharge of neurons within the ventroposterior medial (VPM) thalamus and barrel
      field (BF) somatosensory cortex of awake animals using multichannel extracellular
      recording strategies. The present findings indicate two primary outcomes that
      result from increasing frequencies of LC stimulation, either an inverted-U
      facilitating response profile or monotonic suppression of sensory-evoked neuronal
      responses. Increased tonic LC output generally decreased neuronal response
      latency measures for both BF cortical and VPM thalamic cells. LC-mediated effects
      on target VPM and BF cortical neuron sensory processing are consistent with
      previous demonstrations of NE modulatory actions on central neurons but indicate
      that such actions are cell specific. Moreover, clear differences were observed
      between the modulation of VPM and BF cortical cells. These data suggest that
      sensory signal processing is continually altered over the range of tonic LC
      discharge frequencies that occur in the waking animal. Such changes may account
      for LC-mediated shifts in sensory network performance across multiple stages of
      arousal and attention.

PMID- 15574729
TI  - The generation of dopaminergic neurons by human neural stem cells is enhanced by
      Bcl-XL, both in vitro and in vivo.
AB  - Progress in stem cell biology research is enhancing our ability to generate
      specific neuron types for basic and applied studies and to design new treatments
      for neurodegenerative diseases. In the case of Parkinson's disease (PD),
      alternative human dopaminergic (DAergic) neurons other than primary fetal tissue
      do not yet exist. One possible source could be human neural stem cells (hNSCs),
      although the yield in DAergic neurons and their survival are very limited. [see
      figure]. In this study, we found that Bcl-X(L) enhances (one-to-two orders of
      magnitude) the capacity for spontaneous dopaminergic differentiation of hNSCs,
      which then exceeds that of cultured human ventral mesencephalic tissue. Bcl-X(L)
      also enhanced total neuron generation by hNSCs, but to a lower extent. Neuronal
      phenotypes other than DA were not affected by Bcl-X(L), indicating an exquisitely
      specific effect on DAergic neurons. In vivo, grafts of Bcl-X(L)-overexpressing
      hNSCs do generate surviving human TH+ neurons in the adult rat 6-OH-dopamine
      lesioned striatum, something never seen when naive hNSCs were transplanted. Most
      of the data obtained here in terms of the effects of Bcl-X(L) are consistent with
      an enhanced survival type of mechanism and not supportive of induction,
      specification, or proliferation of DAergic precursors. From this in vitro and in
      vivo evidence, we conclude that enhancing Bcl-X(L) expression is important to
      obtain human DAergic neurons from hNSCs. These findings may facilitate the
      development of drug-screening and cell-replacement activities to discover new
      therapeutic strategies for PD.

PMID- 15574730
TI  - Rho-kinase inhibition enhances axonal plasticity and attenuates cold hyperalgesia
      after dorsal rhizotomy.
AB  - Dorsal rhizotomy results in primary deafferentation of the dorsal horn with
      concomitant sprouting of spared intraspinal monoaminergic axons. Because
      descending monoaminergic systems are thought to mitigate nociceptive transmission
      from the periphery and because dorsal rhizotomy can result in neuropathic pain,
      we sought to determine whether the rhizotomy-induced sprouting response could be
      further augmented. Because myelin-derived molecules mask endogenous plasticity of
      CNS axons and because myelin-inhibitory signaling occurs through the Rho-GTPase
      pathway, we inhibited Rho-pathway signaling after cervical dorsal rhizotomy in
      rats. An increase in the density of serotonergic- and tyrosine hydroxylase
      positive fibers was seen in the dorsal horn 1 week after septuple rhizotomy, and
      axon density continued to increase for at least 1 month. One week after septuple
      rhizotomy, administration of intrathecal Y-27632, an antagonist of Rho-kinase
      (ROCK), increased the density of both fiber types over vehicle-treated controls.
      To examine behavioral effects of both cervical rhizotomy and ROCK inhibition, we
      examined responses to evoked pain: mechanical and thermal allodynia and cold
      hyperalgesia in the forepaw were examined after single, double, and quadruple
      rhizotomies of dorsal roots of the brachial plexus. The most notable behavioral
      outcome was the development of cold hyperalgesia in the affected forepaw after
      rhizotomies of the C7 and C8 dorsal roots. Application of Y-27632 both attenuated
      cold hyperalgesia and induced monoaminergic plasticity after C7/8 rhizotomy.
      Thus, inhibition of Rho-pathway signaling both promoted the sprouting of intact
      supraspinal monoaminergic fibers and alleviated pain after dorsal rhizotomy.

PMID- 15574731
TI  - Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor
      cAMP-induced survival and axonal regeneration of adult retinal ganglion cells.
AB  - We have shown previously that intraocular elevation of cAMP using the cAMP analog
      8-(4-chlorophenylthio)-cAMP (CPT-cAMP) failed to promote axonal regeneration of
      axotomized adult retinal ganglion cells (RGCs) into peripheral nerve (PN) grafts
      but significantly potentiated ciliary neurotrophic factor (CNTF)-induced axonal
      regeneration. Using the PN graft model, we now examine the mechanisms underlying
      spontaneous and CNTF/CPT-cAMP-induced neuronal survival and axonal regrowth. We
      found that blockade of the cAMP pathway executor protein kinase A (PKA) using the
      cell-permeable inhibitor KT5720 did not affect spontaneous survival and axonal
      regeneration but essentially abolished the CNTF/CPT-cAMP-induced RGC survival and
      axonal regeneration. Blockade of CNTF signaling pathways such as
      phosphotidylinositol 3-kinase (PI3K)/akt by 2-(4-morpholinyl)-8-phenyl-4H-1
      benzopyran-4-one (LY294002), mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) by 2-(2-diamino-3
      methoxyphenyl-4H-1-benzopyran-4-one (PD98059), or Janus kinase (JAK)/signal
      transducer and activators of transcription (STAT3) by tyrphostin AG490 also
      blocked the CNTF/CPT-cAMP-dependent survival and regeneration effects. PKA
      activity assay and Western blots showed that KT5720, LY294002, and PD98059 almost
      completely inhibited PKA, PI3K/akt, and MAPK/ERK signal transduction,
      respectively, whereas AG490 substantially decreased JAK/STAT3 signal
      transduction. Intraocular injection of CPT-cAMP resulted in a small PKA-dependent
      increase in CNTF receptor alpha mRNA expression in the retinas, an effect that
      may facilitate CNTF action on survival and axonal regeneration. Surprisingly, in
      the absence of CNTF/CPT-cAMP, LY294002, PD98059, and AG490, but not KT5720,
      significantly enhanced spontaneous RGC survival, suggesting differential roles of
      these pathways in RGC survival under different conditions. Our data suggest that
      CNTF/CPT-cAMP-induced RGC survival and axonal regeneration are a result of
      multiple pathway actions, with PKA as an essential component, but that these
      pathways can function in an antagonistic manner under different conditions.

PMID- 15574732
TI  - The mental retardation protein PAK3 contributes to synapse formation and
      plasticity in hippocampus.
AB  - Mutations of the gene coding for PAK3 (p21-activated kinase 3) are associated
      with X-linked, nonsyndromic forms of mental retardation (MRX) in which the only
      distinctive clinical feature is the cognitive deficit. The mechanisms through
      which PAK3 mutation produces the mental handicap remain unclear, although an
      involvement in the mechanisms that regulate the formation or plasticity of
      synaptic networks has been proposed. Here we show, using a transient transfection
      approach, that antisense and small interfering RNA-mediated suppression of PAK3
      or expression of a dominant-negative PAK3 carrying the human MRX30 mutation in
      rat hippocampal organotypic slice cultures results in the formation of abnormally
      elongated dendritic spines and filopodia-like protrusions and a decrease in
      mature spine synapses. Ultrastructural analysis of the changes induced by
      expression of PAK3 carrying the MRX30 mutation reveals that many elongated spines
      fail to express postsynaptic densities or contact presynaptic terminals. These
      defects are associated with a reduced spontaneous activity, altered expression of
      AMPA-type glutamate receptors, and defective long-term potentiation. Together,
      these data identify PAK3 as a key regulator of synapse formation and plasticity
      in the hippocampus and support interpretations that these defects might
      contribute to the cognitive deficits underlying this form of mental retardation.

PMID- 15574733
TI  - Mapping netrin receptor binding reveals domains of Unc5 regulating its tyrosine
      phosphorylation.
AB  - Netrin and its receptors Unc5 and deleted in colorectal carcinoma (DCC) regulate
      axon guidance and cell migration. We defined domains involved in the interactions
      between netrin-1, DCC, and Unc5c. We show that Unc5 requires both Ig domains to
      interact with netrin. DCC binds through the fourth fibronectin type III domain,
      whereas netrin binds through multiple domains to both receptors. We examined the
      functional consequences of removing the netrin binding and nonbinding domains
      from Unc5 in vitro and in vivo. In human embryonic kidney 293 cells, removal of
      the netrin binding second Ig domain causes an increase in basal tyrosine
      phosphorylation, whereas removal of the netrin nonbinding thrombospondin domains
      decreases tyrosine phosphorylation. Moreover, experiments in Caenorhabditis
      elegans indicate that both netrin binding and nonbinding domains are necessary
      for phenotypic rescue of an unc-5 loss of function mutation.

PMID- 15574734
TI  - Direct excitation of inhibitory interneurons by extracellular ATP mediated by
      P2Y1 receptors in the hippocampal slice.
AB  - ATP is an important cell-to-cell signaling molecule mediating the interactions
      between astrocytes and neurons in the CNS. In the hippocampal slices, ATP
      suppresses excitatory transmission mostly through activation of adenosine A1
      receptors, because the ectoenzyme activity for the extracellular breakdown of ATP
      to adenosine is high in slice preparations in contrast to culture environments.
      Because the hippocampus is also rich in the expression of P2 receptors activated
      specifically by ATP, we examined whether ATP modulates neuronal excitability in
      the acute slice preparations independently of adenosine receptors. Although ATP
      decreased the frequency of spontaneously occurring EPSCs in the CA3 pyramidal
      neurons through activation of adenosine A1 receptors, ATP concurrently increased
      the frequency of IPSCs in a manner dependent on action potential generation. This
      effect was mediated by P2Y1 receptors because (1) 2-methylthio-ATP (2meSATP) was
      the most potent agonist, (2) 2'-deoxy-N6-methyladenosine-3',5'-bisphosphate
      diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC
      frequency was not observed in the transgenic mice lacking P2Y1 receptor proteins.
      Application of 2meSATP elicited MRS2179-sensitive time- and voltage-dependent
      inward currents in the interneurons, which depolarized the cell to firing
      threshold. Also, it increased [Ca2+]i in both astrocytes and interneurons, but,
      unlike the former effect, the latter was entirely dependent on Ca2+ entry. Thus,
      in hippocampal slices, in addition to activating A1 receptors of the excitatory
      terminals after being converted to adenosine, ATP activates P2Y1 receptors in the
      interneurons, which is linked to activation of unidentified excitatory
      conductance, through mechanisms distinct from those in the astrocytes.

PMID- 15574735
TI  - A novel Ca2+-independent signaling pathway to extracellular signal-regulated
      protein kinase by coactivation of NMDA receptors and metabotropic glutamate
      receptor 5 in neurons.
AB  - The specification and organization of glutamatergic synaptic transmission require
      the coordinated interaction among glutamate receptors and their synaptic adaptor
      proteins closely assembled in the postsynaptic density (PSD). Here we
      investigated the interaction between NMDA receptors and metabotropic glutamate
      receptor 5 (mGluR5) in the integral regulation of extracellular signal-regulated
      protein kinase (ERK) and gene expression in cultured rat striatal neurons. We
      found that coapplication of NMDA and the mGluR5 agonist (S)-3,5
      dihydroxyphenylglycine synergistically increased ERK phosphorylation.
      Interestingly, the synergistic increase in ERK phosphorylation was dependent on
      the cross talk between NMDA receptor-associated synaptic adaptor protein PSD-95
      and the mGluR5-linked adaptor protein Homer1b/c but not on the conventional Ca2+
      signaling derived from NMDA receptors (Ca2+ influx) and mGluR5 (intracellular
      Ca2+ release). This was demonstrated by the findings that the synergistic
      phosphorylation of ERK induced by coactivation of NMDA receptors and mGluR5 was
      blocked by either a Tat peptide that disrupts NMDA receptor/PSD-95 binding or
      small interfering RNAs that selectively reduce cellular levels of Homer1b/c.
      Furthermore, ERK activated through this PSD-95/Homer1b/c-dependent and Ca2+
      independent pathway was able to phosphorylate the two key transcription factors
      Elk-1 and cAMP response element-binding protein, which further leads to
      facilitation of c-Fos expression. Together, we have identified a novel Ca2+
      independent signaling pathway to ERK by the synergistic interaction of NMDA
      receptors and mGluR5 via their adaptor proteins in the PSD of neurons, which
      underlies a synapse-to-nucleus communication important for the transcriptional
      regulation.

PMID- 15574736
TI  - Nuclear calcium/calmodulin regulates memory consolidation.
AB  - The neuronal response to a Ca2+ stimulus is a complex process involving direct
      Ca2+/calmodulin (CaM) actions as well as secondary activation of multiple
      signaling pathways such as cAMP and ERK (extracellular signal-regulated kinase).
      These signals can act in both the cytoplasm and the nucleus to control gene
      expression. To dissect the role of nuclear from cytoplasmic Ca2+/CaM signaling in
      memory formation, we generated transgenic mice that express a dominant inhibitor
      of Ca2+/CaM selectively in the nuclei of forebrain neurons and only after the
      animals reach adulthood. These mice showed diminished neuronal activity-induced
      phosphorylation of cAMP response element-binding protein, reduced expression of
      activity-induced genes, altered maximum levels of hippocampal long-term
      potentiation, and severely impaired formation of long-term, but not short-term,
      memory. Our results demonstrate that nuclear Ca2+/CaM signaling plays a critical
      role in memory consolidation in the mouse.

PMID- 15574737
TI  - Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate
      neuroendocrine responses to stress and exploratory locomotor activity:
      application of recombinant adenovirus containing 5-HT1A sequences.
AB  - Our previous studies found that serotonin transporter (SERT) knock-out mice
      showed increased sensitivity to minor stress and increased anxiety-like behavior
      but reduced locomotor activity. These mice also showed decreased density of 5
      hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal
      raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these
      phenotypes of SERT knock-out mice, two studies were conducted. Recombinant
      adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad
      1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The
      expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they
      are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP
      sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in
      the medial hypothalamus; this effect was accompanied by elimination of the
      exaggerated adrenocorticotropin responses to a saline injection (minor stress)
      and reduced locomotor activity but not by a change in increased exploratory
      anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad
      1AP-antisense was injected into the hypothalamus of normal mice. The density and
      the function of 5-HT1A receptors in the medial hypothalamus were significantly
      reduced in Ad-1AP-antisense-treated mice. Compared with the control group
      (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant
      reduction in locomotor activity, but again no changes in exploratory anxiety-like
      behaviors, tested by elevated plus-maze and open-field tests. Thus, the present
      results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress
      responses and locomotor activity but may not regulate exploratory anxiety-like
      behaviors.

PMID- 15574738
TI  - Strong calcium entry activates mitochondrial superoxide generation, upregulating
      kinase signaling in hippocampal neurons.
AB  - Large increases in cytosolic free Ca2+ ([Ca2+]i) activate several kinases that
      are important for neuronal plasticity, including Ca2+/calmodulin-dependent kinase
      II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC). Because it is
      also known, mainly in non-neuronal systems, that superoxide radicals (O2-)
      activate these (and other) kinases and because O2- generation by mitochondria is
      in part [Ca2+]i dependent, we examined in hippocampal neurons the relationship
      between Ca2+ entry, O2- production, and kinase activity. We found that, after
      large stimulus-induced [Ca2+]i increases, O2- selectively produced by
      mitochondria near plasmalemmal sites of Ca2+ entry acts as a modulator to
      upregulate the two kinases, namely, CaMKII and PKA, whose activities are directly
      or indirectly phosphorylation dependent. The common mechanism involves O2-
      inhibition of inactivating protein phosphatases. Conversely, because small
      [Ca2+]i increases do not promote mitochondrial respiration and O2- generation,
      weak stimuli favor enhanced phosphatase activity, which therefore leads to
      suppressed kinase activity. Enhanced O2- production also promoted PKC activity
      but by a phosphatase-independent pathway. These results suggest that Ca2+
      dependent upregulation of mitochondrial O2- production may be a general mechanism
      for linking Ca2+ entry to enhanced kinase activity and therefore to synaptic
      plasticity. This mechanism also represents yet another way that mitochondria,
      acting as calcium sensors, can play a role in neuronal signal transduction.

PMID- 15574739
TI  - Isolation of a novel platelet-derived growth factor-responsive precursor from the
      embryonic ventral forebrain.
AB  - Oligodendrocyte progenitor cells express platelet-derived growth factor (PDGF)
      receptor-alpha and, when expanded in PDGF only, have been shown to generate
      oligodendrocytes and astrocytes but never neurons. Recent evidence suggests that
      oligodendrocytes are generated by a common progenitor that also generates neurons
      but not astrocytes. We used the neurosphere culture system to isolate embryonic
      ventral forebrain, PDGF-responsive precursors (PRPs). We report that the medial
      ganglionic eminence is the source of PRP-generated neurospheres and that the
      progeny can differentiate into parvalbumin-positive interneurons,
      oligodendrocytes, and astrocytes. Thyroid hormone and bone morphogenetic protein
      2 (BMP-2) promote the mutually exclusive differentiation of oligodendrocytes and
      neurons, respectively, whereas ciliary neurotrophic factor acts with BMP-2 to
      suppress OLIG2 expression and promote astroglial differentiation. PRPs require
      fibroblast growth factor-2 together with PDGF to maintain self-renewal, which is
      dependent on sonic hedgehog signaling. We present evidence for forebrain
      oligodendrocytes and parvalbumin-positive interneurons being generated by a
      common precursor and elucidate signals regulating the multiple differentiation
      routes of the progeny of this precursor.

PMID- 15574740
TI  - Enhanced inhibitory synaptic transmission in the cerebellar molecular layer of
      the GluRdelta2 knock-out mouse.
AB  - A novel ionotropic glutamate receptor subunit delta2 (GluRdelta2), which is
      specifically expressed in cerebellar Purkinje neurons (PNs), is implicated in the
      induction of long-term depression. Mutant mice deficient in GluRdelta2 (delta2-/
      ) have abnormal cerebellar synaptic organization and impaired motor coordination
      and learning. Previous in vivo extracellular recordings indelta2-/- revealed that
      PN activity distinct from that in wild-type (WT) mice is attributable to enhanced
      climbing fiber activity. Here, we report that GABAergic synaptic transmission was
      enhanced in the molecular layer of the cerebellar cortex in delta2-/-. Optical
      recordings in cerebellar slice preparations indicated that application of
      bicuculline, a GABA(A) receptor antagonist, increased the amplitude and area of
      excitation propagation more in delta2-/- than in WT. Whole-cell patch-clamp
      recordings from PNs demonstrated that miniature IPSC (mIPSC) amplitude were
      larger in delta2-/- than in WT. Also, rebound potentiation (RP), a type of long
      lasting inhibitory synaptic potentiation inducible by postsynaptic depolarization
      of PNs in WT, was not induced in slices prepared from delta2-/-. In contrast, RP
      was induced in cultured PNs prepared from delta2-/-. Pharmacologic activation of
      climbing fibers in WT in vivo increased mIPSC amplitudes in PNs and prevented RP
      induction. These results suggest that enhanced climbing fiber activity in delta2
      /- potentiates IPSC amplitudes in PNs through RP in vivo, resulting in the
      prevention of additional RP induction.

PMID- 15574741
TI  - Peroxisome-proliferator-activated receptor gamma induces a clearance mechanism
      for the amyloid-beta peptide.
AB  - We investigated whether peroxisome proliferator-activated receptor gamma
      (PPARgamma) could be involved in the modulation of the amyloid cascade causing
      Alzheimer's disease. Inducing expression or activating PPARgamma using synthetic
      agonists of the thiazolinedione family results in a dramatic decrease in the
      levels of the amyloid-beta (Abeta) peptide in the conditioned medium of neuronal
      and non-neuronal cells. PPARgamma does not affect expression or activity of any
      of the secretases involved in the generation of the Abeta peptide but induces a
      fast, cell-bound clearing mechanism responsible for the removal of the Abeta
      peptide from the medium. Although PPARgamma expression is generally low in the
      CNS, induction of PPARgamma expression during inflammation could be beneficial
      for inducing Abeta clearance. We confirm that the Abeta clearance mechanism can
      indeed be induced by PPARgamma activation in primary murine-mixed glia and
      cortical neuronal cultures. Our results suggest that PPARgamma-controlled
      mechanisms should be explored further as potential drug targets for Alzheimer's
      disease treatment.

PMID- 15574742
TI  - N-cadherin juxtamembrane domain modulates voltage-gated Ca2+ current via RhoA
      GTPase and Rho-associated kinase.
AB  - The juxtamembrane domain (JMD) of N-cadherin cytoplasmic tail is an important
      regulatory region of the clustering and adhesion activities of the protein. In
      addition, the JMD binds a diversity of proteins capable of modifying
      intracellular processes including cytoskeletal rearrangement mediated by Rho
      GTPases. These GTPases also function as regulators of voltage-activated calcium
      channels, which in turn modulate neuronal excitability. The present study was
      designed to determine whether there is a direct functional link, via Rho GTPase,
      between the N-cadherin JMD and these voltage-activated channels. It was found
      that the infusion of the soluble JMD into chick ciliary neurons causes a
      substantial decrease in the amplitude of the high-threshold voltage-activated
      (HVA) calcium current. The activation time is increased while the inactivation
      process is reduced, suggesting that the decreased current amplitude reflects a
      reduction in the number of channels available to open. This effect was reversed
      by inhibition of RhoA or its downstream effector, Rho-associated kinase (ROCK).
      Because ROCK determines the active state of myosin, these results suggest that
      the modulation of HVA by the JMD could be mediated by changes in the status of
      the actin-myosin cytoskeleton.

PMID- 15574743
TI  - Single-channel behavior of heteromeric alpha1beta glycine receptors: an attempt
      to detect a conformational change before the channel opens.
AB  - The alpha1beta heteromeric receptors are likely to be the predominant synaptic
      form of glycine receptors in the adult. Their activation mechanism was
      investigated by fitting putative mechanisms to single-channel recordings obtained
      at four glycine concentrations (10-1000 microm) from rat alpha1beta receptors,
      expressed in human embryonic kidney 293 cells. The adequacy of each mechanism,
      with its fitted rate constants, was assessed by comparing experimental dwell time
      distributions, open-shut correlations, and the concentration-open probability
      (P(open)) curve with the predictions of the model. A good description was
      obtained only if the mechanism had three glycine binding sites, allowed both
      partially and fully liganded openings, and predicted the presence of open-shut
      correlations. A strong feature of the data was the appearance of an increase in
      binding affinity as more glycine molecules bind, before the channel opens. One
      interpretation of this positive binding cooperativity is that binding sites
      interact, each site sensing the state of ligation of the others. An alternative,
      and novel, explanation is that agonist binding stabilizes a higher affinity form
      of the receptor that is produced by a conformational change ("flip") that is
      separate from, and precedes, channel opening. Both the "interaction" scheme and
      the flip scheme describe our data well, but the latter has fewer free parameters
      and above all it offers a mechanism for the affinity increase. Distinguishing
      between the two mechanisms will be important for our understanding of the
      structural dynamics of activation in the nicotinic superfamily and is important
      for our understanding of mutations in these receptors.

PMID- 15574744
TI  - The neural mechanisms for minimizing cross-modal distraction.
AB  - The neural circuitry that increases attention to goal-relevant stimuli when we
      are in danger of becoming distracted is a matter of active debate. To address
      several long-standing controversies, we asked participants to identify a letter
      presented either visually or auditorily while we varied the amount of cross-modal
      distraction from an irrelevant letter in the opposite modality. Functional
      magnetic resonance imaging revealed three novel results. First, activity in
      sensory cortices that processed the relevant letter increased as the irrelevant
      letter became more distracting, consistent with a selective increase of attention
      to the relevant letter. In line with this view, an across-subjects correlation
      indicated that the larger the increase of activity in sensory cortices that
      processed the relevant letter, the less behavioral interference there was from
      the irrelevant letter. Second, regions of the dorsolateral prefrontal cortex
      (DLPFC) involved in orienting attention to the relevant letter also participated
      in increasing attention to the relevant letter when conflicting stimuli were
      present. Third, we observed a novel pattern of regional specialization within the
      cognitive division of the anterior cingulate cortex (ACC) for focusing attention
      on the relevant letter (dorsal ACC) versus detecting conflict from the irrelevant
      letter (rostral ACC). These findings indicate novel roles for sensory cortices,
      the DLPFC, and the ACC in increasing attention to goal-relevant stimulus
      representations when distracting stimuli conflict with behavioral objectives.
      Furthermore, they potentially resolve a long-standing controversy regarding the
      key contribution of the ACC to cognitive control.

PMID- 15574745
TI  - Frequency-dependent modulation of retinogeniculate transmission by serotonin.
AB  - The relay of visual information converging in the lateral geniculate nucleus
      (LGN) en route to the visual cortex is modulated by projections from brainstem
      nuclei. The release of serotonin, one mediator of these effects, has been shown
      to act at a presynaptic site to inhibit neurotransmitter release at the
      retinogeniculate synapse, the connection between retinal ganglion cells and
      thalamocortical relay neurons in the LGN. To understand how serotonergic
      inhibition of synaptic transmission influences the transfer of information at
      this synapse, we examined the EPSCs and firing responses of relay neurons to 5
      carboxytryptamine (5-CT), a 5-HT1 receptor agonist that preferentially activates
      the presynaptic over postsynaptic modulatory effects of serotonin. Bath
      application of 5-CT inhibits synaptic strength, relieves synaptic depression, and
      reduces the total synaptic charge transferred at the retinogeniculate synapse in
      mouse LGN brain slices. In contrast, 5-CT does not significantly alter the
      membrane potential response of relay neurons to trains of intracellular current
      injections. Here we show that presynaptic serotonergic modulation results in a
      frequency-dependent inhibition of relay neuron firing. At low-frequency
      stimulation, 5-CT markedly reduces charge transfer at the retinogeniculate
      synapse, thus inhibiting relay neuron firing. However, inhibition of firing by 5
      CT is diminished during high-frequency stimulation, because relief from synaptic
      depression partially offsets the reduction in charge transfer. Thus, presynaptic
      serotonergic inhibition plays a powerful role in modulating the frequency range
      of visual information transmitted via the retinogeniculate synapse such that high
      frequency inputs are more reliably transmitted than low-frequency inputs.

PMID- 15574746
TI  - Apoptosis-inducing factor substitutes for caspase executioners in NMDA-triggered
      excitotoxic neuronal death.
AB  - The profound neuroprotection observed in poly(ADP-ribose) polymerase-1 (PARP-1)
      null mice to ischemic and excitotoxic injury positions PARP-1 as a major mediator
      of neuronal cell death. We report here that apoptosis-inducing factor (AIF)
      mediates PARP-1-dependent glutamate excitotoxicity in a caspase-independent
      manner after translocation from the mitochondria to the nucleus. In primary
      murine cortical cultures, neurotoxic NMDA exposure triggers AIF translocation,
      mitochondrial membrane depolarization, and phosphatidyl serine exposure on the
      cell surface, which precedes cytochrome c release and caspase activation. NMDA
      neurotoxicity is not affected by broad-spectrum caspase inhibitors, but it is
      prevented by Bcl-2 overexpression and a neutralizing antibody to AIF. These
      results link PARP-1 activation with AIF translocation in NMDA-triggered
      excitotoxic neuronal death and provide a paradigm in which AIF can substitute for
      caspase executioners.

PMID- 15574747
TI  - Acid-induced pain and its modulation in humans.
AB  - Despite the discovery of ion channels that are activated by protons, we still
      know relatively little about the signaling of acid pain. We used a novel
      technique, iontophoresis of protons, to investigate acid-induced pain in human
      volunteers. We found that transdermal iontophoresis of protons consistently
      caused moderate pain that was dose-dependent. A marked desensitization occurred
      with persistent stimulation, with a time constant of approximately 3 min.
      Recovery from desensitization occurred slowly, over many hours. Acid-induced pain
      was significantly augmented in skin sensitized by acute topical application of
      capsaicin. However, skin desensitized by repeated capsaicin application showed no
      significant reduction in acid-induced pain, suggesting that both capsaicin
      sensitive and insensitive sensory neurons contribute to acid pain. Furthermore,
      topical application of non-steroidal anti-inflammatory drugs (NSAIDs)
      significantly attenuated acid-evoked pain but did not affect the heat pain
      threshold, suggesting a specific interaction between NSAIDs and peripheral acid
      sensors. Subcutaneous injection of amiloride (1 mm) also significantly inhibited
      the pain induced by iontophoresis of acid, suggesting an involvement of acid
      sensing ion channel (ASIC) receptors. Conversely, iontophoresis of acid over a
      wide range of skin temperatures from 4 to 40 degrees C produced only minor
      changes in the induced pain. Together these data suggest a prominent role for
      ASIC channels and only a minor role for transient receptor potential vanilloid
      receptor-1 as mediators of cutaneous acid-induced pain.

PMID- 15574748
TI  - Phosphatidylinositol [correction] 4,5-bisphosphate signals underlie receptor
      specific Gq/11-mediated modulation of N-type Ca2+ channels.
AB  - Modulation of voltage-gated Ca2+ channels via G-protein-coupled receptors is a
      prime mechanism regulating neurotransmitter release and synaptic plasticity.
      Despite extensive studies, the molecular mechanism underlying Gq/11-mediated
      modulation remains unclear. We found cloned and native N-type Ca2+ channels to be
      regulated by phosphatidylinositol [correction] 4,5-bisphosphate (PIP2). In inside
      out oocyte patches, PIP2 greatly attenuated or reversed the observed rundown of
      expressed channels. In sympathetic neurons, muscarinic M1 ACh receptor
      suppression of the Ca2+ current (ICa) was temporally correlated with PIP2
      hydrolysis, blunted by PIP2 in whole-cell pipettes, attenuated by expression of
      PIP2-sequestering proteins, and became irreversible when PIP2 synthesis was
      blocked. We also probed mechanisms of receptor specificity. Although bradykinin
      also induced PIP2 hydrolysis, it did not inhibit ICa. However, bradykinin
      receptors became nearly as effective as M1 receptors when PIP2 synthesis, IP3
      receptors, or the activity of neuronal Ca2+ sensor-1 were blocked, suggesting
      that bradykinin receptor-induced intracellular Ca2+ increases stimulate PIP2
      synthesis, compensating for PIP2 hydrolysis. We suggest that differential use of
      PIP2 signals underlies specificity of Gq/11-coupled receptor actions on the
      channels

PMID- 15574749
TI  - Chronic exposure to rotenone models sporadic Parkinson's disease in Drosophila
      melanogaster.
AB  - Parkinson's disease (PD) is a movement disorder characterized by the selective
      degeneration of nigrostriatal dopaminergic neurons. Both familial and sporadic
      cases present tremor, rigidity, slowness of movement, and postural instability.
      Although major insights into the genes responsible for some rare hereditary cases
      have arisen, the etiology of sporadic cases remains unknown. Epidemiological
      studies have suggested an association with environmental toxins, mainly
      mitochondrial complex I inhibitors such as the widely used pesticide rotenone. In
      recent years, Drosophila melanogaster has been used as a model of several
      neurodegenerative diseases, including a genetic model of PD. Here, we studied the
      neurodegenerative and behavioral effects of a sublethal chronic exposure to
      rotenone in Drosophila. After several days, the treated flies presented
      characteristic locomotor impairments that increased with the dose of rotenone.
      Immunocytochemistry analysis demonstrated a dramatic and selective loss of
      dopaminergic neurons in all of the brain clusters. The addition of l-dopa (3,4
      dihydroxy-L-phenylalanine) into the feeding medium rescued the behavioral
      deficits but not neuronal death, as is the case in human PD patients. In
      contrast, the antioxidant melatonin (N-acetyl-5-methoxytryptamine) alleviated
      both symptomatic impairment and neuronal loss, supporting the idea that this
      agent may be beneficial in the treatment of PD. Therefore, chronic exposure to
      pesticides recapitulates key aspects of PD in Drosophila and provides a new in
      vivo model for studying the mechanisms of dopaminergic neurodegeneration.

PMID- 15574750
TI  - Shark cartilage, cancer and the growing threat of pseudoscience.
AB  - The promotion of crude shark cartilage extracts as a cure for cancer has
      contributed to at least two significant negative outcomes: a dramatic decline in
      shark populations and a diversion of patients from effective cancer treatments.
      An alleged lack of cancer in sharks constitutes a key justification for its use.
      Herein, both malignant and benign neoplasms of sharks and their relatives are
      described, including previously unreported cases from the Registry of Tumors in
      Lower Animals, and two sharks with two cancers each. Additional justifications
      for using shark cartilage are illogical extensions of the finding of
      antiangiogenic and anti-invasive substances in cartilage. Scientific evidence to
      date supports neither the efficacy of crude cartilage extracts nor the ability of
      effective components to reach and eradicate cancer cells. The fact that people
      think shark cartilage consumption can cure cancer illustrates the serious
      potential impacts of pseudoscience. Although components of shark cartilage may
      work as a cancer retardant, crude extracts are ineffective. Efficiencies of
      technology (e.g., fish harvesting), the power of mass media to reach the lay
      public, and the susceptibility of the public to pseudoscience amplifies the
      negative impacts of shark cartilage use. To facilitate the use of reason as the
      basis of public and private decision-making, the evidence-based mechanisms of
      evaluation used daily by the scientific community should be added to the training
      of media and governmental professionals. Increased use of logical, collaborative
      discussion will be necessary to ensure a sustainable future for man and the
      biosphere.

PMID- 15574751
TI  - Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts.
AB  - The role of myofibroblasts in tissue repair and fibrosis is well documented, but
      the source of these myofibroblasts is unclear. There is evidence of a circulating
      population of fibrocytes that can home to areas of injury and contribute to
      myofibroblast populations. Previously, we have shown that the bone marrow is a
      source of myofibroblasts for many tissues including the gut, lung, and kidney and
      that this phenomenon is exacerbated by injury. We now show that the bone marrow
      can contribute to myofibroblast and fibroblast populations in tumor stroma in a
      mouse model of pancreatic insulinoma. Mice transgenic for the rat insulin
      promoter II gene linked to the large-T antigen of SV40 (RIPTag) develop solid
      beta-cell tumors of the pancreas. Approximately 25% of myofibroblasts in these
      pancreatic tumors were donor-derived, and these were concentrated toward the edge
      of the tumor. Thus, the development of tumor stroma is at least in part a
      systemic response that may ultimately yield methods of targeting new therapy.

PMID- 15574752
TI  - Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis
      induced by aberrant activation of Wnt signaling.
AB  - Wnt signaling plays a crucial role in a number of developmental processes and in
      tumorigenesis. beta-Catenin is stabilized by Wnt signaling and associates with
      the TCF/LEF family of transcription factors, thereby activating transcription of
      Wnt target genes. Constitutive activation of beta-catenin-TCF-mediated
      transcription resulting from mutations in adenomatous polyposis coli (APC), beta
      catenin, or Axin is believed to be a critical step in tumorigenesis among
      divergent types of cancers. Here we show that the transactivation potential of
      the beta-catenin-TCF complex is enhanced by its interaction with a BCL9-like
      protein, B9L, in addition to BCL9. We found that B9L is required for enhanced
      beta-catenin-TCF-mediated transcription in colorectal tumor cells and for beta
      catenin-induced transformation of RK3E cells. Furthermore, expression of B9L was
      aberrantly elevated in about 43% of colorectal tumors, relative to the
      corresponding noncancerous tissues. These results suggest that B9L plays an
      important role in tumorigenesis induced by aberrant activation of Wnt signaling.

PMID- 15574753
TI  - TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric
      mice.
AB  - Tumor necrosis factor (TNF) family ligand TNF-alpha and Fas ligand (FasL) can
      trigger apoptosis in solid tumors, but their clinical usage has been limited by
      hepatotoxicity. TNF-related apoptosis-inducing ligand (TRAIL) is a newly
      identified member of the TNF family, and its clinical application currently is
      under a similar debate. Here, we report a recombinant soluble form of human TRAIL
      (114 to 281 amino acids) that induces apoptosis in tumor cells but not human
      hepatocytes. We first isolated human hepatocytes from patients and showed that
      the human hepatocytes expressed Fas but no TRAIL death receptor DR4 and little
      DR5 on the cell surface. Antibody cross-linked FasL, but not TRAIL, triggered
      apoptosis of the human hepatocytes through cleavage of caspases. We then examined
      TRAIL hepatotoxicity in severe combined immunodeficient/Alb-uPA chimeric mice
      harboring human hepatocytes. Intravenous injection of FasL, but not TRAIL, caused
      apoptotic death of human hepatocytes within the chimeric liver, thus killing the
      mice. Finally, we showed that repeated intraperitoneal injections of TRAIL
      inhibited intraperitoneal and subcutaneous tumor growth without inducing
      apoptosis in human hepatocytes in these chimeric mice. The results indicate that
      the recombinant soluble human TRAIL has a profound apoptotic effect on tumor
      cells but is nontoxic to human hepatocytes in vitro and in vivo.

PMID- 15574754
TI  - Identification of a binding partner for the endothelial cell surface proteins
      TEM7 and TEM7R.
AB  - Tumor endothelial marker 7 (TEM7) was recently identified as an mRNA transcript
      overexpressed in the blood vessels of human solid tumors. Here, we identify
      several new variants of TEM7, derived by alternative splicing, that are predicted
      to be intracellular (TEM7-I), secreted (TEM7-S), or on the cell surface membrane
      (TEM7-M) of tumor endothelium. Using new antibodies against the TEM7 protein, we
      confirmed the predicted expression of TEM7 on the cell surface and demonstrated
      that TEM7-M protein, like its mRNA, is overexpressed on the endothelium of
      various tumor types. We then used an affinity purification strategy to search for
      TEM7-binding proteins and identified cortactin as a protein capable of binding to
      the extracellular region of both TEM7 and its closest homologue, TEM7-related
      (TEM7R), which is also expressed in tumor endothelium. The binding domain of
      cortactin was mapped to a unique nine-amino acid region in its plexin-like
      domain. These studies establish the overexpression of TEM7 protein in tumor
      endothelium and provide new opportunities for the delivery of therapeutic and
      imaging agents to the vessels of solid tumors.

PMID- 15574755
TI  - 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid, a small
      molecule isocoumarin, potentiates dexamethasone-induced apoptosis of human
      multiple myeloma cells.
AB  - 2-(8-Hydroxy-6-methoxy-1-oxo-1Eta-2-benzopyran-3-yl)propionic acid (NM-3) is a
      small molecule isocoumarin derivative that has recently entered clinical trials
      as an orally bioavailable anticancer agent. NM-3 induces lethality of human
      carcinoma cells by both apoptotic and nonapoptotic mechanisms and potentiates the
      effects of cytotoxic chemotherapeutic agents. The present studies have evaluated
      the effects of NM-3 on human multiple myeloma (MM) cells. The results demonstrate
      that NM-3 potentiates dexamethasone-induced killing of both dexamethasone
      sensitive MM1.S and dexamethasone-resistant RPMI8226 and U266 MM cells. We show
      that NM-3 enhances dexamethasone-induced release of the mitochondrial apoptogenic
      factors cytochrome c and Smac/DIABLO. The results also demonstrate that NM-3
      enhances dexamethasone-induced activation of the intrinsic caspase-9->caspase-3
      apoptotic pathway. In concert with these results, NM-3 potentiates dexamethasone
      induced apoptosis of MM1.S cells. Moreover, NM-3 acts synergistically with
      dexamethasone in inducing apoptosis of the dexamethasone-resistant RPMI8226 and
      U266 MM cells. These findings indicate that NM-3 may be effective in combination
      with dexamethasone in the treatment of MM.

PMID- 15574756
TI  - Analysis of diepoxide-specific cyclic N-terminal globin adducts in mice and rats
      after inhalation exposure to 1,3-butadiene.
AB  - 1,3-Butadiene is an important industrial chemical used in the production of
      synthetic rubber and is also found in gasoline and combustion products. It is a
      multispecies, multisite carcinogen in rodents, with mice being the most sensitive
      species. 1,3-Butadiene is metabolized to several epoxides that form DNA and
      protein adducts. Previous analysis of 1,2,3-trihydroxybutyl-valine globin adducts
      suggested that most adducts resulted from 3-butene-1,2-diol metabolism to 3,4
      epoxy-1,2-butanediol, rather than from 1,2;3,4-diepoxybutane. To specifically
      examine metabolism of 1,3-butadiene to 1,2;3,4-diepoxybutane, the formation of
      the 1,2;3,4-diepoxybutane-specific adduct N,N-(2,3-dihydroxy-1,4-butadiyl)-valine
      was evaluated in mice treated with 3, 62.5, or 1250 ppm 1,3-butadiene for 10 days
      and rats exposed to 3 or 62.5 ppm 1,3-butadiene for 10 days, or to 1000 ppm 1,3
      butadiene for 90 days, using a newly developed immunoaffinity liquid
      chromatography tandem mass spectrometry assay. In addition, 2-hydroxy-3-butenyl
      valine and 1,2,3-trihydroxybutyl-valine adducts were determined. The analyses of
      several adducts derived from 1,3-butadiene metabolites provided new insight into
      species and exposure differences in 1,3-butadiene metabolism. Mice formed much
      higher amounts of N,N-(2,3-dihydroxy-1,4-butadiyl)-valine than rats. The
      formation of 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)
      valine was similar in mice exposed to 3 or 62.5 ppm 1,3-butadiene, whereas 2
      hydroxy-3-butenyl-valine was 3-fold higher at 1250 ppm. In both species, 1,2,3
      trihydroxybutyl-valine adducts were much higher than 2-hydroxy-3-butenyl-valine
      and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine. Together, these data show that 1,3
      butadiene is primarily metabolized via the 3-butene-1,2-diol pathway, but that
      mice are much more efficient at forming 1,2;3,4-diepoxybutane than rats,
      particularly at low exposures. This assay should also be readily adaptable to
      molecular epidemiology studies on 1,3-butadiene-exposed workers.

PMID- 15574757
TI  - Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA
      damage: implications for gastric carcinogenesis.
AB  - Oxidative stress is linked to carcinogenesis due to its ability to damage DNA.
      The human gastric pathogen Helicobacter pylori exerts much of its pathogenicity
      by inducing apoptosis and DNA damage in host gastric epithelial cells. Polyamines
      are abundant in epithelial cells, and when oxidized by the inducible spermine
      oxidase SMO(PAOh1) H(2)O(2) is generated. Here, we report that H. pylori up
      regulates mRNA expression, promoter activity, and enzyme activity of SMO(PAOh1)
      in human gastric epithelial cells, resulting in DNA damage and apoptosis. H.
      pylori-induced H(2)O(2) generation and apoptosis in these cells was equally
      attenuated by an inhibitor of SMO(PAOh1), by catalase, and by transient
      transfection with small interfering RNA targeting SMO(PAOh1). Conversely,
      SMO(PAOh1) overexpression induced apoptosis to the same levels as caused by H.
      pylori. Importantly, in H. pylori-infected tissues, there was increased
      expression of SMO(PAOh1) in both human and mouse gastritis. Laser capture
      microdissection of human gastric epithelial cells demonstrated expression of
      SMO(PAOh1) that was significantly attenuated by H. pylori eradication. These
      results identify a pathway for oxidative stress-induced epithelial cell apoptosis
      and DNA damage due to SMO(PAOh1) activation by H. pylori that may contribute to
      the pathogenesis of the infection and development of gastric cancer.

PMID- 15574758
TI  - Defective DNA strand break repair after DNA damage in prostate cancer cells:
      implications for genetic instability and prostate cancer progression.
AB  - Together with cell cycle checkpoint control, DNA repair plays a pivotal role in
      protecting the genome from endogenous and exogenous DNA damage. Although
      increased genetic instability has been associated with prostate cancer
      progression, the relative role of DNA double-strand break repair in malignant
      versus normal prostate epithelial cells is not known. In this study, we
      determined the RNA and protein expression of a series of DNA double-strand break
      repair genes in both normal (PrEC-epithelial and PrSC-stromal) and malignant
      (LNCaP, DU-145, and PC-3) prostate cultures. Expression of genes downstream of
      ATM after ionizing radiation-induced DNA damage reflected the p53 status of the
      cell lines. In the malignant prostate cell lines, mRNA and protein levels of the
      Rad51, Xrcc3, Rad52, and Rad54 genes involved in homologous recombination were
      elevated approximately 2- to 5-fold in comparison to normal PrEC cells. The
      XRCC1, DNA polymerase-beta and -delta proteins were also elevated. There were no
      consistent differences in gene expression relating to the nonhomologous end
      joining pathway. Despite increased expression of DNA repair genes, malignant
      prostate cancer cells had defective repair of DNA breaks, alkali-labile sites,
      and oxidative base damage. Furthermore, after ionizing radiation and mitomycin C
      treatment, chromosomal aberration assays confirmed that malignant prostate cells
      had defective DNA repair. This discordance between expression and function of DNA
      repair genes in malignant prostate cancer cells supports the hypothesis that
      prostate tumor progression may reflect aberrant DNA repair. Our findings support
      the development of novel treatment strategies designed to reinstate normal DNA
      repair in prostate cancer cells.

PMID- 15574759
TI  - Prognostic relevance of gene amplifications and coamplifications in breast
      cancer.
AB  - Multiple different oncogenes have been described previously to be amplified in
      breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification
      results in oncogene overexpression but may also serve as an indicator of genomic
      instability. As such, presence of one or several gene amplifications may have
      prognostic significance. To assess the prognostic importance of amplifications
      and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we
      analyzed a breast cancer tissue microarray containing samples from 2197 cancers
      with follow-up information. Fluorescence in situ hybridizations revealed
      amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and
      EGFR in 0.8% of the tumors. All gene amplifications were significantly associated
      with high grade. HER2 (P < 0.001) and MYC amplification (P < 0.001) were also
      linked to shortened survival. In case of HER2, this was independent of grade, pT,
      and pN categories. MYC amplification was almost 3 times more frequent in
      medullary cancer (15.9%), than in the histologic subtype with the second highest
      frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated
      with estrogen receptor/progesterone receptor negativity (P < 0.001) whereas CCND1
      amplification was linked to estrogen receptor/progesterone receptor positivity (P
      < 0.001). Coamplifications were more prevalent than expected based on the
      individual frequencies. Coamplifications of one or several other oncogenes
      occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of
      EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than
      tumors with only one of these amplifications. Furthermore, a gradual decrease of
      survival was observed with increasing number of amplifications. In conclusion,
      these data support a major prognostic impact of genomic instability as determined
      by a broad gene amplification survey in breast cancer.

PMID- 15574760
TI  - Array comparative genomic hybridization analysis of genomic alterations in breast
      cancer subtypes.
AB  - In this study, we performed high-resolution array comparative genomic
      hybridization with an array of 4153 bacterial artificial chromosome clones to
      assess copy number changes in 44 archival breast cancers. The tumors were flow
      sorted to exclude non-tumor DNA and increase our ability to detect gene copy
      number changes. In these tumors, losses were more frequent than gains, and gains
      in 1q and loss in 16q were the most frequent alterations. We compared gene copy
      number changes in the tumors based on histologic subtype and estrogen receptor
      (ER) status, i.e., ER-negative infiltrating ductal carcinoma, ER-positive
      infiltrating ductal carcinoma, and ER-positive infiltrating lobular carcinoma. We
      observed a consistent association between loss in regions of 5q and ER-negative
      infiltrating ductal carcinoma, as well as more frequent loss in 4p16, 8p23, 8p21,
      10q25, and 17p11.2 in ER-negative infiltrating ductal carcinoma compared with ER
      positive infiltrating ductal carcinoma (adjusted P values < or = 0.05). We also
      observed high-level amplifications in ER-negative infiltrating ductal carcinoma
      in regions of 8q24 and 17q12 encompassing the c-myc and c-erbB-2 genes and
      apparent homozygous deletions in 3p21, 5q33, 8p23, 8p21, 9q34, 16q24, and 19q13.
      ER-positive infiltrating ductal carcinoma showed a higher frequency of gain in
      16p13 and loss in 16q21 than ER-negative infiltrating ductal carcinoma.
      Correlation analysis highlighted regions of change commonly seen together in ER
      negative infiltrating ductal carcinoma. ER-positive infiltrating lobular
      carcinoma differed from ER-positive infiltrating ductal carcinoma in the
      frequency of gain in 1q and loss in 11q and showed high-level amplifications in
      1q32, 8p23, 11q13, and 11q14. These results indicate that array comparative
      genomic hybridization can identify significant differences in the genomic
      alterations between subtypes of breast cancer.

PMID- 15574761
TI  - Analysis of gene expression patterns and chromosomal changes associated with
      aging.
AB  - Age is the largest single risk factor for the development of cancer in mammals.
      Age-associated chromosomal changes, such as aneuploidy and telomere erosion, may
      be vitally involved in the initial steps of tumorigenesis. However, changes in
      gene expression specific for increased aneuploidy with age have not yet been
      characterized. Here, we address these questions by using a panel of fibroblast
      cell lines and lymphocyte cultures from young and old age groups. Oligonucleotide
      microarrays were used to characterize the expression of 14,500 genes. We measured
      telomere length and analyzed chromosome copy number changes and structural
      rearrangements by multicolor interphase fluorescence in situ hybridization and 7
      fluorochrome multiplex fluorescence in situ hybridization, and we tried to show a
      relationship between gene expression patterns and chromosomal changes. These
      analyses revealed a number of genes involved in both the cell cycle and
      proliferation that are differently expressed in aged cells. More importantly, our
      data show an association between age-related aneuploidy and the gene expression
      level of genes involved in centromere and kinetochore function and in the
      microtubule and spindle assembly apparatus. To verify that some of these genes
      may also be involved in tumorigenesis, we compared the expression of these genes
      in chromosomally stable microsatellite instability and chromosomally unstable
      chromosomal instability colorectal tumor cell lines. Three genes (Notch2, H2AFY2,
      and CDC5L) showed similar expression differences between microsatellite
      instability and chromosomal instability cell lines as observed between the young
      and old cell cultures suggesting that they may play a role in tumorigenesis.

PMID- 15574762
TI  - Gene expression profiling for molecular characterization of inflammatory breast
      cancer and prediction of response to chemotherapy.
AB  - Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer
      with a 5-year survival limited to approximately 40%. Diagnosis, based on clinical
      and/or pathological criteria, may be difficult. Optimal systemic neoadjuvant
      therapy and accurate predictors of pathological response have yet to be defined
      for increasing response rate and survival. Using DNA microarrrays containing
      approximately 8,000 genes, we profiled breast cancer samples from 81 patients,
      including 37 with IBC and 44 with noninflammatory breast cancer (NIBC). Global
      unsupervised hierarchical clustering was able to some extent to distinguish IBC
      and NIBC cases and revealed subclasses of IBC. Supervised analysis identified a
      109-gene set the expression of which discriminated IBC from NIBC samples. This
      molecular signature was validated in an independent series of 26 samples, with an
      overall performance accuracy of 85%. Discriminator genes were associated with
      various cellular processes possibly related to the aggressiveness of IBC,
      including signal transduction, cell motility, adhesion, and angiogenesis. A
      similar approach, with leave-one-out cross-validation, identified an 85-gene set
      that divided IBC patients with significantly different pathological complete
      response rate (70% in one group and 0% in the other group). These results show
      the potential of gene expression profiling to contribute to a better
      understanding of IBC, and to provide new diagnostic and predictive factors for
      IBC, as well as for potential therapeutic targets.

PMID- 15574763
TI  - Gene expression in the lung of p53 mutant mice exposed to cigarette smoke.
AB  - We showed previously that p53 mutations play a role in cigarette smoke-related
      carcinogenesis not only in humans but also in A/J mice. In fact, (UL53-3 x
      A/J)F(1) mice, carrying a dominant-negative germ-line p53 mutation, responded to
      exposure to environmental cigarette smoke more efficiently than their wild-type
      (wt) littermate controls in terms of molecular alterations, cytogenetic damage,
      and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA
      array the expression of 1,185 cancer-related genes in the lung of the same mice.
      Neither environmental cigarette smoke nor the p53 status affected the expression
      of the p53 gene, but the p53 mutation strikingly increased the basal levels of
      p53 nuclear protein in the lung. Environmental cigarette smoke increased p53
      protein levels in wt mice only. The p53 mutation enhanced the expression of
      positive cell cycle regulators in sham-exposed mice, which suggests a physiologic
      protective role of p53. In environmental cigarette smoke-exposed mice, the p53
      mutation resulted in a lack of induction of proapoptotic genes and in
      overexpression of genes involved in cell proliferation, signal transduction,
      angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted
      to environmental cigarette smoke in a similar manner regarding genes involved in
      metabolism of xenobiotics, multidrug resistance, and protein repair. Irrespective
      of the p53 status, environmental cigarette smoke poorly affected the expression
      of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these
      findings may explain the increased susceptibility of p53 mutant mice to smoke
      related alterations of intermediate biomarkers and lung carcinogenesis.

PMID- 15574764
TI  - Overexpression of activating transcription factor-2 is required for tumor growth
      and progression in mouse skin tumors.
AB  - Activating transcription factor (ATF)-2 is a member of the ATF/cyclic AMP
      responsive element binding protein family of transcription factors. It has been
      shown, in vitro, to possess growth factor-independent proliferation and
      transformation capacity. The information concerning the involvement of ATF-2 in
      carcinogenesis is rather limited. In a previous report, we showed a progressive
      increase in the levels of various activator protein (AP)-1 components, including
      phosphorylated ATF-2, in a series of mouse skin cell lines that represented
      developmental stages of the mouse skin carcinogenesis system. In the present
      study, we examined in detail the role of ATF-2 in the development of mouse skin
      spindle cells A5 and CarB, which correspond to the late and most aggressive stage
      of the mouse skin carcinogenesis model. To address this issue, we overexpressed a
      dominant negative form of ATF-2 in the A5 and CarB cell lines and examined their
      behavior in vitro and in vivo at the molecular and cellular level. The stable
      transfectants expressed decreased levels of phosphorylated ATF-2 and c-Jun.
      Subsequently, we observed that dominant negative ATF-2 affected the composition
      and reduced the activity of AP-1. The above biochemical changes were followed,
      both in vitro and in vivo in BALB/c severe combined immunodeficient mice, by
      suppression of the aggressive characteristics of the A5 and CarB mouse skin
      spindle cells. We attributed this behavior to the significant down-regulation of
      cyclin D1, cyclin A, and ATF-3, known AP-1 targets implicated in cell cycle
      control and promotion. In conclusion, our findings underscore a key regulatory
      role of ATF-2 in tumor growth and progression of mouse skin tumors.

PMID- 15574765
TI  - Identification and testing of a gene expression signature of invasive carcinoma
      cells within primary mammary tumors.
AB  - We subjected cells collected using an in vivo invasion assay to cDNA microarray
      analysis to identify the gene expression profile of invasive carcinoma cells in
      primary mammary tumors. Expression of genes involved in cell division, survival,
      and cell motility were most dramatically changed in invasive cells indicating a
      population that is neither dividing nor apoptotic but intensely motile. In
      particular, the genes coding for the minimum motility machine that regulates beta
      actin polymerization at the leading edge and, therefore, the motility and
      chemotaxis of carcinoma cells, were dramatically up-regulated. However, ZBP1,
      which restricts the localization of beta-actin, the substrate for the minimum
      motility machine, was down-regulated. This pattern of expression implicated ZBP1
      as a suppressor of invasion. Reexpression of ZBP1 in metastatic cells with
      otherwise low levels of ZBP1 reestablished normal patterns of beta-actin mRNA
      targeting and suppressed chemotaxis and invasion in primary tumors. ZBP1
      reexpression also inhibited metastasis from tumors. These experiments support the
      involvement in metastasis of the pathways identified in invasive cells, which are
      regulated by ZBP1.

PMID- 15574766
TI  - In vitro and in vivo models analyzing von Hippel-Lindau disease-specific
      mutations.
AB  - Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene cause tissue
      specific tumors, with a striking genotype-phenotype correlation. Loss of VHL
      expression predisposes to hemangioblastoma and clear cell renal cell carcinoma,
      whereas specific point mutations predispose to pheochromocytoma, polycythemia, or
      combinations of hemangioblastoma, renal cell carcinoma, and/or pheochromocytoma.
      The VHL protein (pVHL) has been implicated in many cellular activities including
      the hypoxia response, cell cycle arrest, apoptosis, and extracellular matrix
      remodeling. We have expressed missense pVHL mutations in Vhl(-/-) murine
      embryonic stem cells to test genotype-phenotype correlations in euploid cells. We
      first examined the ability of mutant pVHL to direct degradation of the hypoxia
      inducible factor (HIF) subunits HIF1alpha and HIF2alpha. All mutant pVHL proteins
      restored proper hypoxic regulation of HIF1alpha, although one VHL mutation
      (VHL(R167Q)) displayed impaired binding to Elongin C. This mutation also failed
      to restore HIF2alpha regulation. In separate assays, these embryonic stem cells
      were used to generate teratomas in immunocompromised mice, allowing independent
      assessment of the effects of specific VHL mutations on tumor growth.
      Surprisingly, teratomas expressing the VHL(Y112H) mutant protein displayed a
      growth disadvantage, despite restoring HIFalpha regulation. Finally, we observed
      increased microvessel density in teratomas derived from Vhl(-/-) as well as
      VHL(Y112H), VHL(R167Q), and VHL(R200W) embryonic stem cells. Together, these
      observations support the hypothesis that pVHL plays multiple roles in the cell,
      and that these activities can be separated via discrete VHL point mutations. The
      ability to dissect specific VHL functions with missense mutations in a euploid
      model offers a novel opportunity to elucidate the activities of VHL as a tumor
      suppressor.

PMID- 15574767
TI  - CXCR4 regulates growth of both primary and metastatic breast cancer.
AB  - The chemokine receptor CXCR4 and its cognate ligand CXCL12 recently have been
      proposed to regulate the directional trafficking and invasion of breast cancer
      cells to sites of metastases. However, effects of CXCR4 on the growth of primary
      breast cancer tumors and established metastases and survival have not been
      determined. We used stable RNAi to reduce expression of CXCR4 in murine 4T1
      cells, a highly metastatic mammary cancer cell line that is a model for stage IV
      human breast cancer. Using noninvasive bioluminescence and magnetic resonance
      imaging, we showed that knockdown of CXCR4 significantly limited the growth of
      orthotopically transplanted breast cancer cells. Mice in which parental 4T1 cells
      were implanted had progressively enlarging tumors that spontaneously
      metastasized, and these animals all died from metastatic disease. Remarkably,
      RNAi of CXCR4 prevented primary tumor formation in some mice, and all mice
      transplanted with CXCR RNAi cells survived without developing macroscopic
      metastases. To analyze effects of CXCR4 on metastases to the lung, an organ
      commonly affected by metastatic breast cancer, we injected tumor cells
      intravenously and monitored cell growth with bioluminescence imaging. Inhibiting
      CXCR4 with RNAi, or the specific antagonist AMD3100, substantially delayed the
      growth of 4T1 cells in the lung, although neither RNAi nor AMD3100 prolonged
      overall survival in mice with experimental lung metastases. These data indicate
      that CXCR4 is required to initiate proliferation and/or promote survival of
      breast cancer cells in vivo and suggest that CXCR4 inhibitors will improve
      treatment of patients with primary and metastatic breast cancer.

PMID- 15574768
TI  - Coagulation facilitates tumor cell spreading in the pulmonary vasculature during
      early metastatic colony formation.
AB  - Coagulation has long been known to facilitate metastasis. To pinpoint the steps
      where coagulation might play a role in the metastasis, we used three-dimensional
      visualization of direct infusion of fluorescence labeled antibody to observe the
      interaction of tumor cells with platelets and fibrinogen in isolated lung
      preparations. Tumor cells arrested in the pulmonary vasculature were associated
      with a clot composed of both platelets and fibrin(ogen). Initially, the cells
      attached to the pulmonary vessels were rounded. Over the next 2 to 6 hours, they
      spread on the vessel surface. The associated clot was lysed coincident with tumor
      cell spreading. To assess the importance of clot formation, we inhibited
      coagulation with hirudin, a potent inhibitor of thrombin. The number of tumor
      cells initially arrested in the lung of hirudin-treated mice was essentially the
      same as in control mice. However, tumor cell spreading and subsequent retention
      of the tumor cells in the lung was markedly inhibited in the anticoagulated mice.
      These associations of the tumor cells with platelets were independent of tumor
      cell expression of P-selectin ligands. This work identifies tumor cell spreading
      onto the vascular surface as an important component of the metastatic cascade and
      implicates coagulation in this process.

PMID- 15574769
TI  - Increased insulin-like growth factor I receptor expression and signaling are
      components of androgen-independent progression in a lineage-derived prostate
      cancer progression model.
AB  - Apoptosis and inhibition of mitosis are primary mechanisms mediating androgen
      ablation therapy-induced regression of prostate cancer (PCa). However, PCa
      readily becomes androgen independent, leading to fatal disease. Up-regulated
      growth and survival signaling is implicated in development of resistance to
      androgen ablation therapy. We are testing the hypothesis that insulin-like growth
      factor (IGF) responsiveness is required for androgen-independent (AI)
      progression. Using the LNCaP human PCa progression model, we have determined that
      IGF-I-mediated protection from apoptotic stress and enhanced mitotic activity is
      androgen dependent in LNCaP cells but is androgen independent in lineage-derived
      C4-2 cells. Both cell lines exhibit androgen-responsive patterns of IGF-I
      receptor (IGF-IR) expression, activation, and signaling to insulin receptor
      substrate-2 and AKT. However, C4-2 cells express higher levels of IGF-IR mRNA and
      protein and exhibit enhanced IGF-I-mediated phosphorylation and downstream
      signaling under androgen-deprived conditions. In comparisons of naive and AI
      metastatic human PCa specimens, we have confirmed that IGF-IR levels are elevated
      in advanced disease. Together with our LNCaP/C4-2 AI progression model data,
      these results indicate that increased IGF-IR expression is associated with AI
      antiapoptotic and promitotic IGF signaling in PCa disease progression.

PMID- 15574770
TI  - Loss of neural cell adhesion molecule induces tumor metastasis by up-regulating
      lymphangiogenesis.
AB  - Reduced expression of neural cell adhesion molecule (NCAM) has been implicated in
      the progression to tumor malignancy in cancer patients. Previously, we have shown
      that the loss of NCAM function causes the formation of lymph node metastasis in a
      transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2). Here we
      show that tumors of NCAM-deficient Rip1Tag2 transgenic mice exhibit up-regulated
      expression of the lymphangiogenic factors vascular endothelial growth factor
      (VEGF)-C and -D (17% in wild-type versus 60% in NCAM-deficient Rip1Tag2 mice)
      and, with it, increased lymphangiogenesis (0% in wild-type versus 19% in NCAM
      deficient Rip1Tag2 mice). Repression of VEGF-C and -D function by adenoviral
      expression of a soluble form of their cognate receptor, VEGF receptor-3, results
      in reduced tumor lymphangiogenesis (56% versus 28% in control versus treated
      mice) and lymph node metastasis (36% versus 8% in control versus treated mice).
      The results indicate that the loss of NCAM function causes lymph node metastasis
      via VEGF-C- and VEGF-D-mediated lymphangiogenesis. These results also establish
      Rip1Tag2;NCAM-deficient mice as a unique model for stochastic, endogenous tumor
      lymphangiogenesis and lymph node metastasis in immunocompetent mice.

PMID- 15574771
TI  - Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes
      to its transformation and mRNA transport activities.
AB  - The eukaryotic translation initiation factor eIF4E is dysregulated in a wide
      variety of human cancers. In the cytoplasm, eIF4E acts in the rate-limiting step
      of translation initiation whereas in the nucleus, eIF4E forms nuclear bodies and
      promotes the nucleo-cytoplasmic export of a subset of growth-promoting mRNAs
      including cyclin D1. The only known post-translational modification of eIF4E is
      its phosphorylation at S209. Many studies have examined the role of
      phosphorylation on cap-dependent translation. However, no studies to date have
      explored the role of phosphorylation on the ability of eIF4E to transform cells.
      Using mutagenesis and separately a small molecular inhibitor of eIF4E
      phosphorylation, we show that eIF4E phosphorylation enhances both its mRNA
      transport function and its transformation activity in cell culture. Thus,
      phosphorylation of nuclear eIF4E seems to be an important step in control of the
      mRNA transport and thus the transforming properties of eIF4E.

PMID- 15574772
TI  - Elevated Flk1 (vascular endothelial growth factor receptor 2) signaling mediates
      enhanced angiogenesis in beta3-integrin-deficient mice.
AB  - Tumor growth, tumor angiogenesis, and vascular endothelial growth factor (VEGF)
      specific angiogenesis are all enhanced in beta(3)-integrin-null mice.
      Furthermore, endothelial cells isolated from beta(3)-null mice show elevated
      levels of Flk1 (VEGF receptor 2) expression, suggesting that beta(3)-integrin can
      control the amplitude of VEGF responses by controlling Flk1 levels or activity.
      We now show that Flk1 signaling is required for the enhanced tumor growth and
      angiogenesis seen in beta(3)-null mice. Moreover, beta(3)-null endothelial cells
      exhibit enhanced migration and proliferation in response to VEGF in vitro, and
      this phenotype requires Flk1 signaling. Upon VEGF stimulation, beta(3)-null
      endothelial cells exhibit higher levels of phosphorylated Flk1 and extracellular
      related kinases 1 and 2 than wild-type endothelial cells. Furthermore, signaling
      via ERK1/2 is required to mediate the elevated responses to VEGF observed in
      beta(3)-null endothelial cells and aortic rings in vitro. These data confirm that
      VEGF signaling via Flk1 is enhanced in beta(3)-integrin-deficient mice and
      suggests that this increase may mediate the enhanced angiogenesis and tumor
      growth observed in these mice in vivo.

PMID- 15574773
TI  - Transgenic nude mouse with ubiquitous green fluorescent protein expression as a
      host for human tumors.
AB  - We report here the development of the transgenic green fluorescent protein (GFP)
      nude mouse with ubiquitous GFP expression. The GFP nude mouse was obtained by
      crossing nontransgenic nude mice with the transgenic C57/B6 mouse in which the
      beta-actin promoter drives GFP expression in essentially all tissues. In crosses
      between nu/nu GFP male mice and nu/+ GFP female mice, the embryos fluoresced
      green. Approximately 50% of the offspring of these mice were GFP nude mice.
      Newborn mice and adult mice fluoresced very bright green and could be detected
      with a simple blue-light-emitting diode flashlight with a central peak of 470 nm
      and a bypass emission filter. In the adult mice, the organs all brightly
      expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach,
      and duodenum. The following systems were dissected out and shown to have
      brilliant GFP fluorescence: the entire digestive system from tongue to anus; the
      male and female reproductive systems; brain and spinal cord; and the circulatory
      system, including the heart and major arteries and veins. The skinned skeleton
      highly expressed GFP. Pancreatic islets showed GFP fluorescence. The spleen cells
      were also GFP positive. Red fluorescent protein (RFP)-expressing human cancer
      cell lines, including PC-3-RFP prostate cancer, HCT-116-RFP colon cancer, MDA-MB
      435-RFP breast cancer, and HT1080-RFP fibrosarcoma were transplanted to the
      transgenic GFP nude mice. All of these human tumors grew extensively in the
      transgenic GFP nude mouse. Dual-color fluorescence imaging enabled visualization
      of human tumor-host interaction by whole-body imaging and at the cellular level
      in fresh and frozen tissues. The GFP mouse model should greatly expand our
      knowledge of human tumor-host interaction.

PMID- 15574774
TI  - Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies
      and targets alpha1-antitrypsin serpin.
AB  - Proteases exert control over cell behavior and affect many biological processes
      by making proteolytic modification of regulatory proteins. The purpose of this
      paper is to describe novel, important functions of matrix metalloproteinase (MMP)
      26. alpha1-Antitrypsin (AAT) is a serpin, the primary function of which is to
      regulate the activity of neutrophil/leukocyte elastase. Insufficient antiprotease
      activity because of AAT deficiency in the lungs is a contributing factor to early
      onset emphysema. We recently discovered that AAT is efficiently cleaved by a
      novel metalloproteinase, MMP-26, which exhibits an unconventional PH(81)CGVPD Cys
      switch motif and is autocatalytically activated in cells and tissues. An elevated
      expression of MMP-26 in macrophages and polymorphonuclear leukocytes supports the
      functional role of MMP-26 in the AAT cleavage and inflammation. We have
      demonstrated a direct functional link of MMP-26 expression with an estrogen
      dependency and confirmed the presence of the estrogen-response element in the MMP
      26 promoter. Immunostaining of tumor cell lines and biopsy specimen microarrays
      confirmed the existence of the inverse correlations of MMP-26 and AAT in
      cells/tissues. An expression of MMP-26 in the estrogen-dependent neoplasms is
      likely to contribute to the inactivation of AAT, to the follow-up liberation of
      the Ser protease activity, and because of these biochemical events, to promote
      matrix destruction and malignant progression. In summary, we hypothesize that MMP
      26, by cleaving and inactivating the AAT serpin, operates as a unique functional
      link that regulates a coordinated interplay between Ser and metalloproteinases in
      estrogen-dependent neoplasms.

PMID- 15574775
TI  - Transcriptional abnormality of the hsMAD2 mitotic checkpoint gene is a potential
      link to hepatocellular carcinogenesis.
AB  - MAD2 is localized to kinetochores of unaligned chromosomes, where it inactivates
      the anaphase-promoting complex/cyclosome, thus contributing to the production of
      a diffusible anaphase inhibitory signal. Disruption of MAD2 expression leads to
      defects in the mitotic checkpoint, chromosome missegregation, and tumorigenesis.
      However, the mechanism by which deregulation and/or abnormality of hsMAD2
      expression remains to be elucidated. Here, we clone and analyze a approximately
      0.5 kb fragment upstream of hsMAD2 and show that this fragment acts as a strong
      promoter. Transcriptional dysfunction of hsMAD2 is frequently observed in
      hepatocellular carcinoma cells, and down-regulation of hsMAD2 protein expression
      is correlated with transcriptional silencing of the hsMAD2 promoter by
      hypermethylation. These results imply a relationship between transcriptional
      abnormality of this mitotic checkpoint gene and mitotic abnormality in human
      cancers.

PMID- 15574776
TI  - Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion
      by breast cancer and mammary epithelial cells.
AB  - Integrins contribute to progression in many cancers, including breast cancer. For
      example, the interaction of alpha(5)beta(1) with plasma fibronectin causes the
      constitutive invasiveness of human prostate cancer cells. Inhibition of this
      process reduces tumorigenesis and prevents metastasis and recurrence. In this
      study, naturally serum-free basement membranes were used as invasion substrates.
      Immunoassays were used to compare the roles of alpha(5)beta(1) and
      alpha(4)beta(1) fibronectin receptors in regulating matrix metalloproteinase
      (MMP)-1-dependent invasion by human breast cancer and mammary epithelial cells.
      We found that a peptide consisting of fibronectin PHSRN sequence, Ac-PHSRN-NH(2),
      induces alpha(5)beta(1)-mediated invasion of basement membranes in vitro by human
      breast cancer and mammary epithelial cells. PHSRN-induced invasion requires
      interstitial collagenase MMP-1 activity and is suppressed by an equimolar
      concentration of a peptide consisting of the LDV sequence of the fibronectin
      connecting segment, Ac-LHGPEILDVPST-NH(2), in mammary epithelial cells, but not
      in breast cancer cells. This sequence interacts with alpha(4)beta(1), an integrin
      that is often down-regulated in breast cancer cells. Immunoblotting shows that
      the PHSRN peptide stimulates MMP-1 production by serum-free human breast cancer
      and mammary epithelial cells and that the LDV peptide represses PHSRN-stimulated
      MMP-1 production only in mammary epithelial cells. Furthermore, PHSRN stimulates
      MMP-1 activity in breast cancer cells and mammary epithelial cells with a time
      course that closely parallels invasion induction. Thus, down-regulation of
      surface alpha(4)beta(1) during oncogenic transformation may be crucial for
      establishment of the alpha(5)beta(1)-induced, MMP-1-dependent invasive phenotype
      of breast cancer cells.

PMID- 15574777
TI  - Membrane-associated and secreted genes in breast cancer.
AB  - The identification of membrane-associated and secreted genes that are
      differentially expressed is a useful step in defining new targets for the
      diagnosis and treatment of cancer. Extracting information on the subcellular
      localization of genes represented on DNA microarrays is difficult and is limited
      by the incomplete sequence and annotation that is available in existing
      databases. Here we combine a biochemical and bioinformatic approach to identify
      membrane-associated and secreted genes expressed in the MCF-7 breast cancer cell
      line. Our approach is based on the analysis of differential hybridization levels
      of RNAs that have been physically separated by virtue of their association with
      polysomes on the endoplasmic reticulum. This approach is specifically applicable
      to oligonucleotide microarrays such as Affymetrix, which use single-color
      hybridization instead of dual-color competitive hybridizations. Assignment to
      membrane-associated and secreted class membership is based on both the
      differential hybridization levels and an expression threshold, which are
      calculated empirically from data collected on a reference set of known
      cytoplasmic and membrane proteins. This method enabled the identification of 755
      membrane-associated and secreted probe sets expressed in MCF-7 cells for which
      this annotation did not previously exist. The data were used to filter a
      previously reported expression dataset to identify membrane-associated and
      secreted genes which are associated with poor prognosis in breast cancer and
      represent potential targets for diagnosis and treatment. The approach reported
      here should provide a useful tool for the analysis of gene expression patterns,
      identifying membrane-associated or secreted genes with biological relevance that
      have the potential for clinical applications in diagnosis or treatment.

PMID- 15574778
TI  - RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family.
AB  - Activated Ras proteins interact with a broad range of effector proteins to induce
      a diverse series of biological consequences. Although typically associated with
      enhanced growth and transformation, activated Ras may also induce growth
      antagonistic effects such as senescence or apoptosis. It is now apparent that
      some of the growth-inhibitory properties of Ras are mediated via the RASSF family
      of Ras effector/tumor suppressors. To date, four members of this family have been
      identified (Nore1, RASSF1, RASSF2, and RASSF3). We now identify a fifth member of
      this group, RASSF4 (AD037). RASSF4 shows approximately 25% identity with RASSF1A
      and 60% identity with RASSF2. RASSF4 binds directly to activated K-Ras in a GTP
      dependent manner via the effector domain, thus exhibiting the basic properties of
      a Ras effector. Overexpression of RASSF4 induces Ras-dependent apoptosis in 293-T
      cells and inhibits the growth of human tumor cell lines. Although broadly
      expressed in normal tissue, RASSF4 is frequently down-regulated by promoter
      methylation in human tumor cells. Thus, RASSF4 appears to be a new member of the
      RASSF family of potential Ras effector/tumor suppressors.

PMID- 15574779
TI  - Functional analysis of the contribution of RhoA and RhoC GTPases to invasive
      breast carcinoma.
AB  - Although the RhoA and RhoC proteins comprise an important subset of the Rho
      GTPase family that have been implicated in invasive breast carcinomas,
      attributing specific functions to these individual members has been difficult. We
      have used a stable retroviral RNA interference approach to generate invasive
      breast carcinoma cells (SUM-159 cells) that lack either RhoA or RhoC expression.
      Analysis of these cells enabled us to deduce that RhoA impedes and RhoC
      stimulates invasion. Unexpectedly, this analysis also revealed a compensatory
      relationship between RhoA and RhoC at the level of both their expression and
      activation, and a reciprocal relationship between RhoA and Rac1 activation.

PMID- 15574780
TI  - Loss of heterozygosity of chromosome 3p21 is associated with mutant TP53 and
      better patient survival in non-small-cell lung cancer.
AB  - Allelic loss of chromosome region 3p21.3 occurs early and frequently in non-small
      cell lung cancer, and numerous tumor suppressor genes at this locus may be
      targets of inactivation. Using an incident case series study of non-small-cell
      lung cancer, we sought to determine the prevalence of loss of heterozygosity
      (LOH) in the 3p21.3 region and to examine the associations between this
      alteration and patient outcome, exposure to tobacco smoke, occupational asbestos
      exposure, and additional molecular alterations in these tumors. We examined LOH
      at 7 microsatellite markers in the chromosome 3p21.3 region, and LOH was present
      in at least one of the loci examined in 60% (156 of 258) of the tumors, with the
      prevalence of LOH at individual loci ranging from 15 to 56%. Occupational
      asbestos exposure and TP53 mutation were significantly associated with more
      extensive 3p21 LOH. In squamous cell carcinomas, measures of cumulative smoking
      dose were significantly lower in patients with LOH at 3p21, particularly in TP53
      mutant tumors. Examining patient outcome, we found that in squamous cell
      carcinomas, having any LOH in this region was associated with a better overall
      survival (log-rank test, P < 0.04). Together, these results indicate that allelic
      loss at 3p21 can affect patient outcome, and that this loss may initially be
      related to carcinogen exposure, but that extension of this loss is related to
      TP53 mutation status and occupational asbestos exposure.

PMID- 15574781
TI  - Survivin deregulation in beta-tubulin mutant ovarian cancer cells underlies their
      compromised mitotic response to taxol.
AB  - Taxol is one of the most successful drugs for the treatment of cancer because of
      its ability to target tubulin, block cell cycle progression at mitosis, and
      induce apoptosis. Despite the success of Taxol, the development of drug
      resistance hampers its clinical applicability. Herein we report that beta-tubulin
      mutant, Taxol-resistant ovarian cancer cells exhibit defective mitotic response
      to Taxol, even at high concentrations that are sufficient to trigger apoptosis.
      This mitotic response-defective phenotype is independent of p53 status. We have
      found that survivin, the mitosis regulator and inhibitor of apoptosis protein, is
      deregulated in these Taxol-resistant cancer cells; Taxol fails to induce survivin
      levels and survivin phosphorylation in these cells, in contrast to their parental
      drug-sensitive counterparts. Exogenous expression of wild-type survivin is able
      to restore the mitotic response of the resistant cells to Taxol treatment. On the
      other hand, exogenous expression of dominant-negative survivin abrogates the
      Taxol-induced mitotic response in drug-sensitive cancer cells. We have also found
      that overexpression of the mitotic kinase Cdk1, which phosphorylates survivin, is
      unable to restore the Taxol-induced mitotic response in the resistant cells. Our
      results show the importance of survivin for the mitotic response in the context
      of Taxol resistance and provide novel insights into the mechanisms of mitotic
      arrest and apoptosis induced by microtubule-targeting agents.

PMID- 15574782
TI  - Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I
      induced signaling in an autochthonous mouse model of prostate cancer.
AB  - We earlier demonstrated that oral infusion of green tea polyphenols inhibits
      development and progression of prostate cancer in transgenic adenocarcinoma of
      the mouse prostate (TRAMP) model. Evidence indicates that elevated levels of IGF
      I with concomitant lowering of IGF binding protein (IGFBP)-3 are associated with
      increased risk for prostate cancer development and progression. In this study, we
      examined the role of IGF/IGFBP-3 signaling and its downstream and other
      associated events during chemoprevention of prostate cancer by green tea
      polyphenols in TRAMP mice. Our data demonstrated an increase in the levels of IGF
      I, phosphatidylinositol 3'-kinase, phosphorylated Akt (Thr-308), and
      extracellular signal-regulated kinase 1/2 with concomitant decrease in IGFBP-3 in
      dorso-lateral prostate of TRAMP mice during the course of cancer progression,
      i.e., as a function of age. Continuous green tea polyphenol infusion for 24 weeks
      to these mice resulted in substantial reduction in the levels of IGF-I and
      significant increase in the levels of IGFBP-3 in the dorso-lateral prostate. This
      modulation of IGF/IGFBP-3 was found to be associated with an inhibition of
      protein expression of phosphatidylinositol 3'-kinase, phosphorylated forms of Akt
      (Thr-308) and extracellular signal-regulated kinase 1/2. Furthermore, green tea
      polyphenol infusion resulted in marked inhibition of markers of angiogenesis and
      metastasis most notably vascular endothelial growth factor, urokinase plasminogen
      activator, and matrix metalloproteinases 2 and 9. Based on our data, we suggest
      that IGF-I/IGFBP-3 signaling pathway is a prime pathway for green tea polyphenol
      mediated inhibition of prostate cancer that limits the progression of cancer
      through inhibition of angiogenesis and metastasis.

PMID- 15574783
TI  - Inhibition of akt/protein kinase B signaling by naltrindole in small cell lung
      cancer cells.
AB  - The phosphatidylinositol 3-kinase-Akt/protein kinase B (PKB) survival signaling
      is very important for cancer cell survival and growth. Constitutively active
      phosphatidylinositol 3-kinase-Akt/PKB signaling in small cell lung cancer (SCLC)
      is a major factor for the survival of SCLC cells. Inhibitors of this signaling
      pathway would be potential antitumor agents, particularly for SCLC. Here we
      report that naltrindole, which has been used as a classic delta opioid
      antagonist, inhibited growth and induced apoptosis in the three characteristic
      SCLC cell lines, NCI-H69, NCI-H345, and NCI-H510. Naltrindole treatment reduced
      constitutive phosphorylation of Akt/PKB on serine 473 and threonine 308 in cells.
      We found that the levels of constitutive phosphorylation of Akt/PKB on serine 473
      correlate with the sensitivity of the three cell lines to naltrindole treatment.
      Furthermore, naltrindole treatment not only reduced the phosphorylation of the
      Akt/PKB upstream kinase phosphoinositide-dependent kinase-1, but also its
      downstream effectors glycogen synthase kinase-3beta and the Forkhead
      transcription factors AFX and FKHR. DNA array analysis of 205 apoptosis-related
      genes indicated that some Akt/PKB-dependent genes were either up- or down
      regulated by naltrindole. Flow cytometric and microscopic analyses clearly showed
      that naltrindole induced apoptosis in SCLC cells. RNA interference experiments
      confirmed that naltrindole-induced cell death was associated with the Akt/PKB
      survival pathway. Together, these results show that naltrindole is a new
      inhibitor of the Akt/PKB signaling pathway, suggesting that naltrindole could be
      a potential lead for the development of a new type of inhibitors that target the
      constitutively active Akt/PKB signaling-dependent SCLC cells.

PMID- 15574784
TI  - Mechanism of the attenuation of proteolysis-inducing factor stimulated protein
      degradation in muscle by beta-hydroxy-beta-methylbutyrate.
AB  - The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) prevents muscle
      protein degradation in cancer-induced weight loss through attenuation of the
      ubiquitin-proteasome proteolytic pathway. To investigate the mechanism of this
      effect, the action of HMB on protein breakdown and intracellular signaling
      leading to increased proteasome expression by the tumor factor proteolysis
      inducing factor (PIF) has been studied in vitro using murine myotubes as a
      surrogate model of skeletal muscle. A comparison has been made of the effects of
      HMB and those of eicosapentaenoic acid (EPA), a known inhibitor of PIF signaling.
      At a concentration of 50 mumol/L, EPA and HMB completely attenuated PIF-induced
      protein degradation and induction of the ubiquitin-proteasome proteolytic
      pathway, as determined by the "chymotrypsin-like" enzyme activity, as well as
      protein expression of 20S proteasome alpha- and beta-subunits and subunit p42 of
      the 19S regulator. The primary event in PIF-induced protein degradation is
      thought to be release of arachidonic acid from membrane phospholipids, and this
      process was attenuated by EPA, but not HMB, suggesting that HMB might act at
      another step in the PIF signaling pathway. EPA and HMB at a concentration of 50
      mumol/L attenuated PIF-induced activation of protein kinase C and the subsequent
      degradation of inhibitor kappaBalpha and nuclear accumulation of nuclear factor
      kappaB. EPA and HMB also attenuated phosphorylation of p42/44 mitogen-activated
      protein kinase by PIF, thought to be important in PIF-induced proteasome
      expression. These results suggest that HMB attenuates PIF-induced activation and
      increased gene expression of the ubiquitin-proteasome proteolytic pathway,
      reducing protein degradation.

PMID- 15574785
TI  - The prosurvival activity of p53 protects cells from UV-induced apoptosis by
      inhibiting c-Jun NH2-terminal kinase activity and mitochondrial death signaling.
AB  - The cytoprotective function of p53 recently has been exploited as a therapeutic
      advantage for cancer prevention; agents activating the prosurvival activity of
      p53 are shown to prevent UV-induced damages. To explore the mechanisms of p53
      mediated protection from UV-induced apoptosis, we have established stable clones
      of H1299 lung carcinoma cells expressing a temperature-sensitive p53 mutant,
      tsp53(V143A). At the permissive temperature of 32 degrees C, the tsp53(V143A)
      expressing cells were arrested in G(1) phase without the occurrence of apoptosis;
      consistent with this is the preferential induction of genes related to growth
      arrest and DNA damage repair. Previous expression of functional tsp53(V143A) for
      > or =18 hours inhibited the release of proapoptotic molecules from mitochondria
      and protected the cells from UV-induced apoptosis; moreover, it suppressed the
      activation of c-Jun NH(2)-terminal kinase (JNK) signaling and relieved the effect
      of UV on p53 target gene activation. p53 associated with JNK and inhibited its
      kinase activity. Using the p53-null H1299 cells, we showed that inhibition of JNK
      blocked the UV-elicited mitochondrial death signaling and caspase activation. Our
      results suggest that the ability of p53 to bind and inactivate JNK, together with
      the activation of the p53 target genes related to cell cycle arrest and DNA
      damage repair, is responsible for its protection of cells against UV-induced
      apoptosis.

PMID- 15574786
TI  - Proteasomal degradation of topoisomerase I is preceded by c-Jun NH2-terminal
      kinase activation, Fas up-regulation, and poly(ADP-ribose) polymerase cleavage in
      SN38-mediated cytotoxicity against multiple myeloma.
AB  - Topoisomerase I inhibitors are effective anticancer therapies and have shown
      activity in hematologic malignancies. Here we show for the first time that SN38,
      the potent active metabolite of irinotecan, induces c-Jun NH(2)-terminal kinase
      activation, Fas up-regulation, and caspase 8-mediated apoptosis in multiple
      myeloma (MM) cells. Proteasomal degradation of nuclear topoisomerase I has been
      proposed as a resistance mechanism in solid malignancies. SN38-induced
      proteasomal degradation of topoisomerase I was observed during SN38-mediated
      cytotoxicity against MM.1S myeloma cell line but occurred after c-Jun NH(2)
      terminal kinase activation, Fas up-regulation, and poly(ADP-ribose) polymerase
      cleavage and failed to protect cells from apoptosis. Differential toxicity was
      observed against MM cells versus bone marrow stromal cells, and SN38 inhibited
      adhesion-induced up-regulation of MM cell proliferation when MM cells adhere to
      bone marrow stromal cells. In addition, SN38 directly inhibited constitutive and
      inducible interleukin 6 and vascular endothelial growth factor secretion by bone
      marrow stromal cells. Synergy was observed when SN38 was used in combination with
      doxorubicin, bortezomib, as well as poly(ADP-ribose) polymerase inhibitor NU1025
      and Fas-activator CH11. These findings have clinical significance, because
      identification of downstream apoptotic signaling after topoisomerase I inhibition
      will both elucidate mechanisms of resistance and optimize future combination
      chemotherapy against MM.

PMID- 15574787
TI  - Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing
      type 1 innate immunity.
AB  - Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs)
      exhibit potent immunostimulating activity by binding with Toll-like receptor 9
      (TLR9) expressed on antigen-presenting cells. Here, we show that CpG-ODN
      encapsulated in cationic liposomes (CpG-liposomes) improves its incorporation
      into CD11c(+) dendritic cells (DCs) and induces enhanced serum interleukin (IL)
      12 levels compared with unmodified CpG-ODN. CpG-liposome potently activated
      natural killer (NK) cells (84.3%) and NKT cells (48.3%) to produce interferon
      gamma (IFN-gamma), whereas the same dose of unmodified CpG-ODN induced only low
      numbers of IFN-gamma-producing NK cells (12.7%) and NKT cells (1.6%) to produce
      IFN-gamma. In contrast with the NKT cell agonist alpha-galactosylceramide, which
      induces both IFN-gamma and IL-4 production by NKT cells, CpG-liposome only
      induced IFN-gamma production by NKT cells. Such potent adjuvant activities of CpG
      liposome were absent in TLR9-deficient mice, indicating that CpG-liposome was as
      effective as CpG-ODN in stimulating type 1 innate immunity through TLR9. In
      addition to TLR9, at least two other factors, IL-12 production by DCs and direct
      contact between DCs and NK or NKT cells, were essential for inducing type 1
      innate immunity by CpG-liposome. Furthermore, ligation of TLR9 by CpG-liposome
      coencapsulated with ovalbumin (OVA) caused the induction of OVA-specific CTLs,
      which exhibited potent cytotoxicity against OVA-expressing tumor cells. These
      results indicate that CpG-liposome alone or combined with tumor antigen protein
      provides a promising approach for the prevention or therapy of tumors.

PMID- 15574788
TI  - Spontaneous regression of grade 3 vulvar intraepithelial neoplasia associated
      with human papillomavirus-16-specific CD4(+) and CD8(+) T-cell responses.
AB  - Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens
      was studied in six patients affected with grade 3 vulvar intraepithelial
      neoplasia (VIN3, also known as bowenoid papulosis). Five of the patients
      presented with a chronic and persistent disease that relapsed after destructive
      treatments. They showed no detectable anti-HPV blood T-cell responses and no T
      cell intraepidermal vulvar infiltrate containing both CD4+ and CD8+ lymphocytes.
      The last patient had a complete clearance of viral lesions, 8 months after
      disease onset and 2 months after electrocoagulation of <50% of the VIN3 lesions.
      She showed high frequency anti-E6 and anti-E7 effector blood T cells by ex vivo
      ELISpot-IFNgamma assay before clinical regression. Immunohistochemical study of
      her vulvar biopsy revealed a marked dermal infiltrate containing a majority of
      CD4+ T lymphocytes and an epidermal infiltrate made up of both CD4(+) and CD8(+)
      T cells. This seems to be the first evidence of an association between
      spontaneous regression of VIN3 lesions and HPV-specific T-cell responses
      detectable in the blood. Hence, an increase of HPV-specific effector T lymphocyte
      responses by vaccine-based therapeutic strategies might be useful to clear the
      lesions in bowenoid papulosis disease.

PMID- 15574789
TI  - Automated quantitative analysis of HDM2 expression in malignant melanoma shows
      association with early-stage disease and improved outcome.
AB  - The incidence of cutaneous malignant melanoma continues to increase every year,
      and this disease remains the leading cause of skin cancer death in industrialized
      countries. Despite the aggressive nature of advanced melanoma, there are no
      standard biological assays in clinical usage that can predict metastasis. This
      may be due, in part, to the inadequacy of reproducible assessment of protein
      expression using traditional immunohistochemistry. We have previously described a
      novel method of quantitative assessment of protein expression (AQUA) with the
      continuity and accuracy of an ELISA assay but with maintenance of critical
      spatial information. Here, we modify this technology for the evaluation of
      protein expression in melanoma. Using a tissue microarray cohort of 405 melanoma
      lesions and 17 normal skin samples, we analyzed expression of HDM2, the human
      homologue of murine double minute 2 with automated quantitative analysis. We show
      that expression levels in the nucleus are significantly higher in primary
      melanomas than in metastatic lesions. Furthermore, high levels of expression are
      predictive of better outcome. This study demonstrates that quantitative
      assessment of protein expression is useful in melanoma to validate potential
      tissue biomarkers and suggests that human homologue of murine double minute 2 may
      be a valuable prognostic tool for management of malignant melanoma.

PMID- 15574790
TI  - Automated quantitative analysis of tissue microarrays reveals an association
      between high Bcl-2 expression and improved outcome in melanoma.
AB  - The addition of B-cell lymphoma 2 (Bcl-2) antisense to dacarbazine in the
      treatment of metastatic melanoma demonstrates improved response rates and
      progression-free survival when compared with dacarbazine alone. Studies on small
      cohorts of melanoma patients have shown variability in Bcl-2 expression (60%-96%
      positive). We performed quantitative analysis of Bcl-2 expression in a large
      patient cohort to assess the association with outcome. Tissue microarrays
      containing intact melanoma specimens representing 402 patients (339 with
      associated survival data) were analyzed with our AQUA system for automated
      quantitative analysis. Automated, quantitative analysis uses S100 to define
      pixels as melanoma (tumor mask) within the array spot and measures intensity of
      Bcl-2 expression using a Cy5 conjugated antibody within the mask. A continuous
      index score is generated, which is directly proportional to the number of
      molecules per unit area. Scores were divided into quartiles and correlated with
      clinical variables. High Bcl-2 expression was associated with better outcome in
      the entire cohort and among metastatic specimens only (P = 0.004 and P = 0.015,
      respectively). Expression was higher in primary than in metastatic specimens (P <
      0.0001). There was no association between Bcl-2 expression and Breslow depth or
      Clark level. The diverse results within the literature may be due to use of small
      cohorts or variability in staining technique. These results suggest studies are
      needed to evaluate the association between quantitative assessment of Bcl-2
      expression and response to Bcl-2 targeting therapy toward the goal of improved
      response rates to these drugs.

PMID- 15574791
TI  - The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces
      apoptosis via induction of 15-lipoxygenase-1 in colorectal cancer cells.
AB  - Histone deacetylases (HDACs) mediate changes in nucleosome conformation and are
      important in the regulation of gene expression. HDACs are involved in cell cycle
      progression and differentiation, and their deregulation is associated with
      several cancers. HDAC inhibitors have emerged recently as promising
      chemotherapeutic agents. One such agent, suberoylanilide hydroxamic acid, is a
      potent inhibitor of HDACs that causes growth arrest, differentiation, and/or
      apoptosis of many tumor types in vitro and in vivo. Because of its low toxicity,
      suberoylanilide hydroxamic acid is currently in clinical trials for the treatment
      of cancer. HDAC inhibitors induce the expression of <2% of genes in cultured
      cells. In this study, we show that low micromolar concentrations of
      suberoylanilide hydroxamic acid induce the expression of 15-lipoxygenase-1 in
      human colorectal cancer cells. The expression of 15-lipoxygenase-1 correlates
      with suberoylanilide hydroxamic acid-induced increase in 13-S
      hydroxyoctadecadienoic acid levels, growth inhibition, differentiation, and
      apoptosis observed with these cells. Furthermore, specific inhibition of 15
      lipoxygenase-1 significantly reduced the suberoylanilide hydroxamic acid-induced
      effects. These novel findings are the first demonstration of a mechanistic link
      between the induction of 15-lipoxygenase-1 by a HDAC inhibitor and apoptosis in
      cancer cells. This result has important implications for the study of
      suberoylanilide hydroxamic acid and other HDAC inhibitors in the prevention and
      therapy of colorectal cancer and supports future investigations of the mechanisms
      by which HDAC inhibitors up-regulate 15-lipoxygenase-1.

PMID- 15574792
TI  - Respective roles of serological status and blood specific antihuman herpesvirus 8
      antibody levels in human herpesvirus 8 intrafamilial transmission in a highly
      endemic area.
AB  - Transmission of human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's
      sarcoma, occurs mainly during childhood in endemic countries and, to a large
      extent, through intrafamilial contacts. To additionally investigate this familial
      transmission, and especially the role of plasma anti-HHV-8 antibody titers, we
      conducted a large survey in a village from Cameroon, Central Africa, including 92
      families (608 individuals). Plasma samples were tested for specific IgG directed
      against HHV-8 lytic antigens by immunofluorescence assay, and titers were
      determined by 2-fold dilutions. Global HHV-8 seroprevalence was 60%, raising from
      32% under 9 years up to a plateau of around 62% between 15 and 40 years. The
      familial correlation patterns in HHV-8 seropositive/seronegative status showed
      strong dependence from mother to child and between siblings. In contrast, no
      familial correlation in anti-HHV-8 antibody levels was observed among infected
      subjects. In particular, no relationship was observed between the anti-HHV-8
      antibody titer of HHV-8 seropositive mothers and the proportion of their HHV-8
      seropositive children. Furthermore, a random permutation study of the anti-HHV-8
      antibody titers among HHV-8 infected subjects showed that the main risk factor
      for infection was the HHV-8 serologic status and not the antibody level. In
      addition, no correlation was found between anti-HHV-8 antibody levels and buffy
      coat HHV-8 viral loads in a subsample of 95 infected subjects. Overall, these
      results strongly suggest that, in this highly endemic population from Central
      Africa, HHV-8 transmission mainly occurs from mother to child and between
      siblings, and it is independent of plasma antibody levels of HHV-8 infected
      relatives.

PMID- 15574793
TI  - Folate is associated with the natural history of high-risk human
      papillomaviruses.
AB  - Several micronutrients have been implicated in cervical carcinogenesis. However,
      their mode of action is still a matter of speculation. In particular, it is
      unclear whether certain nutrients reduce the probability of acquiring high-risk
      human papillomavirus (HPV) or whether they facilitate the clearance of high-risk
      HPV. We conducted a 24-month prospective follow-up study to test the hypothesis
      that systemic concentrations of folate are associated with the occurrence and
      duration of high-risk HPV infections after controlling for other micronutrients
      (vitamins B(12), A, E, and C, total carotene) and known risk factors for high
      risk HPV infections and cervical cancer. Circulating concentrations of these
      micronutrients and risk factors for cervical cancer were determined in a cohort
      of 345 women who were at risk of developing cervical intraepithelial neoplasia.
      Using the hybrid capture 2 (HC-2) assay, high-risk HPV status was evaluated at 6
      month intervals up to 24 months. All women had at least three consecutive visit
      high-risk HPV test results. Higher folate status was inversely associated with
      becoming HC-2 test-positive [odds ratio (OR): 0.27; 95% confidence interval (CI),
      0.08-0.91; P = 0.04]. Women with higher folate status were significantly less
      likely to be repeatedly HC-2 test-positive (OR: 0.33; 95% CI, 0.13-0.86; P =
      0.02) and more likely to become test-negative during the study (OR: 2.50; 95% CI,
      1.18-5.30; P = 0.02). To our knowledge, this is the first long-term prospective
      follow-up study reporting an independent protective role of higher folate status
      on several aspects of the natural history of high-risk HPV after controlling for
      known risk factors and other micronutrients. Improving folate status in subjects
      at risk of getting infected or already infected with high-risk HPV may have a
      beneficial impact in the prevention of cervical cancer.

PMID- 15574794
TI  - Development of an inhibitory interneuronal circuit in the embryonic spinal cord.
AB  - Locally projecting inhibitory interneurons play a crucial role in the patterning
      and timing of network activity. However, because of their relative
      inaccessibility, little is known about their development or incorporation into
      circuits. In this study, we characterized the functional onset,
      neurotransmitters, rostrocaudal spread, and funicular distribution of one such
      spinal interneuronal circuit during development. The R-interneuron is the avian
      homologue of the mammalian Renshaw cell. Both cell types receive input from
      motoneuron recurrent collaterals and make direct connections back onto
      motoneurons. By stimulating motoneurons projecting in a given ventral root and
      recording the response in adjacent ventral roots, we demonstrate that the R
      interneuron circuit becomes functional between embryonic day 6 (E6) and E7. This
      ventral root response is observed at E11 and at E14 until it can no longer be
      detected at E16. Using bath-applied neurotransmitter receptor antagonists, we
      were able to demonstrate that the circuit is predominately nicotinic and
      GABAergic from E7.5 to E15. We also found a glutamatergic component to the
      pathway throughout this developmental period. The R-interneuron projects three or
      more segments both rostrally and caudally through the ventrolateral funiculus.
      The distribution of this circuit may become more locally focused between E7.5 and
      E15.

PMID- 15574795
TI  - Effect of forelimb use on postnatal development of the forelimb motor
      representation in primary motor cortex of the cat.
AB  - In the cat, the motor representation in motor cortex develops between wk 8 and wk
      13. Motor map development is accompanied by a decrease in the current thresholds
      for evoking movements with a concomitant increase in the number of effective
      sites, an increase in the distal representation, and the representation of
      multijoint synergies. In this study we used intracortical microstimulation in
      anesthetized cats to examine how forelimb motor experiences influence development
      of map characteristics. To promote skilled movements during wks 8-13, animals
      were engaged in daily performance of a prehension task. Forelimb movements were
      prevented by intramuscular botulinum toxin injection or restraint. To determine
      whether experience-dependent changes were permanent, we examined the map in
      different animals between 1 wk and 1 yr after cessation of testing. Promoting
      forelimb use resulted in an increase in the number of sites from which multiple
      joint effects were produced by stimulation and the number of joints represented
      at those sites. The effect was maximal at 1 wk after cessation of testing, and
      became progressively less at 1 mo and at 4 mo. Preventing limb use resulted in a
      decreased number of effective sites, an increase in current thresholds for
      evoking responses, and a decreased representation of joints at multijoint sites.
      Our findings show that the motor map can respond to novel motor demands as it is
      forming during development but that it reverts back to one with the properties of
      a map in a control animal if those demands are not maintained in the animal's
      behavioral repertoire.

PMID- 15574796
TI  - Polyamines modulate AMPA receptor-dependent synaptic responses in immature layer
      v pyramidal neurons.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) mediate
      the majority of fast excitation in the CNS. Receptors lacking GluR2 exhibit
      inward rectification and paired-pulse facilitation (PPF) due to polyamine (PA)
      dependent block and unblock, respectively. In this study, we tested whether
      rectification and PPF in immature, but not mature, pyramidal neurons depend not
      only on the absence of functional GluR2 but also on the level of endogenous PAs.
      Whole cell recordings were obtained from layer V pyramidal neurons of P12-P14 or
      P16-P20 rats in the presence or absence of spermine in the pipette (50 microM).
      Isolated minimal excitatory synaptic responses were obtained, and paired (20 Hz)
      stimuli were used to investigate the rectification index (RI) and paired-pulse
      ratio (PPR). Spermine and its synthetic enzyme, ornithine decarboxylase (ODC),
      expression was examined using immunostaining and Western blot, respectively. At
      the immature stage (<P15) inclusion of intracellular spermine increased
      rectification and PPF for evoked excitatory postsynaptic currents (EPSCs) but had
      little or no effect on either measure in more mature (P16-P20) pyramidal neurons.
      Depletion of PAs reduced rectification suggesting that endogenous PAs play a
      critical role in functional regulation of AMPARs. Spermine immunoreactivity and
      ODC expression in immature rat neocortex (<P15) were greater than more mature
      tissue by approximately 20 and 60%, respectively. These results provide further
      support for the idea that excitatory synapses on immature neocortical pyramidal
      neurons ubiquitously contain AMPA receptors lacking the GluR2 subunit and that
      the level of endogenous PAs plays an important role in modulating AMPAR-dependent
      neurotransmission.

PMID- 15574797
TI  - 7 to 12 Hz activity in rat gustatory cortex reflects disengagement from a fluid
      self-administration task.
AB  - The 7 to 12 Hz rhythm is a high-voltage oscillatory phenomenon recorded in many
      rat neocortical regions, largely analogous to the rodent and human somatosensory
      mu rhythm. Central to any interpretation of the functional significance of this
      pattern is the analysis of the behavioral context associated with it. Much of the
      debate on the function of mu, variously believed to represent either an
      environment-oriented or -isolated state, has relied primarily on its association
      with quiet immobility. In this report, we describe the relationship between the 7
      to 12 Hz rhythm and a more complex behavioral setting, in which we were able to
      dissociated task orientation from disengagement. We trained head-restrained,
      water-restricted rats to perform a simple variant of a timed fluid self
      administration task, while recording local field potentials from gustatory cortex
      (GC). Rats progressed through two behavioral states that were clearly
      distinguishable on the basis of lever-pressing regimes: a task-oriented state and
      a second state that reflected disengagement from the task. Concurrent GC neural
      recordings revealed bilaterally coherent oscillations in the 7 to 12 Hz range
      associated solely with the latter state. Consistent with published recordings of
      mu rhythm from somatosensory cortex, these rhythmic episodes were endogenously
      quenched when the rats prepared to lever-press; this inhibition of rhythmic
      episodes lasted through fluid delivery and consumption, making it clear that GC
      rhythms are not related to gustatory processing itself. By showing a direct
      relationship between the 7 to 12 Hz rhythm and disengagement from a task, these
      data provide strong and novel evidence that this gustatory rhythm in rats is
      associated with withdrawal from experimental contingencies.

PMID- 15574798
TI  - Roles of M2 and M4 muscarinic receptors in regulating acetylcholine release from
      myenteric neurons of mouse ileum.
AB  - We investigated the subtype of presynaptic muscarinic receptors associated with
      inhibition of acetylcholine (ACh) release in the mouse small intestine. We
      measured endogenous ACh released from longitudinal muscle with myenteric plexus
      (LMMP) preparations obtained from M1-M5 receptor knockout (KO) mice. Electrical
      field stimulation (EFS) increased ACh release in all LMMP preparations obtained
      from M1-M5 receptor single KO mice. The amounts of ACh released in all
      preparations were equal to that in the wild-type mice. Atropine further increased
      EFS-induced ACh release in the wild-type mice. Unexpectedly, atropine also
      increased, to a similar extent, EFS-induced ACh release to the wild-type mice in
      all M1-M5 receptor single KO mice. In M2 and M4 receptor double KO mice, the
      amount of EFS-induced ACh release was equivalent to an atropine-evoked level in
      the wild-type mouse, and further addition of atropine had no effect. M2 receptor
      immunoreactivity was located in both smooth muscle cells and enteric neurons. M4
      receptor immunoreactivity was located in the enteric neurons, being in co
      localization with M2 receptor immunoreactivity. These results indicate that both
      M2 and M4 receptors mediate the muscarinic autoinhibition in ACh release in the
      LMMP preparation of the mouse ileum, and loss of one of these subtypes can be
      compensated functionally by a receptor that remained. M1, M3, and M5 receptors do
      not seem to be involved in this mechanism.

PMID- 15574799
TI  - Time course of changes in brain activity and functional connectivity associated
      with long-term adaptation to a rotational transformation.
AB  - The purpose of this study was to examine the time course of changes in cerebral
      activity and functional connectivity during long-term adaptation to a visuomotor
      transformation. Positron emission tomography was used to measure changes in brain
      activity as subjects tracked a target under the influence of a rotational
      transformation that distorted visual feedback. The experiment was 1 week long and
      consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining
      early and late stages of learning. On average, visuomotor adaptation was achieved
      within 3 days. During early stages of adaptation, better performance was
      associated with greater activity in brain areas related to attention including
      bilateral dorso- and ventrolateral prefrontal cortices, frontal eye fields, and
      the human homologue of area MT. However, as adaptation proceeded, improvements in
      performance were associated with greater activity in motor regions such as the
      left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left
      cingulate motor area, right putamen, and a nonmotor region within the middle
      temporal gyrus. This learning-specific shift in brain activity was associated
      with a progressive change in the functional connectivity of these regions toward
      the end of the first session. Interestingly, only the functional connections
      between the anterior cerebellum, left middle temporal gyrus, and left
      sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our
      findings suggest that visuomotor adaptation is not only reflected in persistent
      changes in activity in motor-related regions, but also in the strengthening and
      maintenance of specific functional connections.

PMID- 15574800
TI  - Motion mechanisms in macaque MT.
AB  - The macaque middle temporal area (MT) is exquisitely sensitive to visual motion
      and there is a large amount of evidence that neural activity in MT is tightly
      correlated with the perception of motion. The mechanisms by which MT neurons
      achieve their directional selectivity, however, have received considerably less
      attention. We investigated the motion-energy model as a description of motion
      mechanisms in macaque MT. We first confirmed one of the predictions of the motion
      energy model; macaques-just like humans-perceive a reversed direction of motion
      when a stimulus reverses contrast with every displacement (reverse-phi). This
      reversal of perceived direction had a clear correlate in the neural responses of
      MT cells, which were predictive of the monkey's behavioral decisions. Second, we
      investigated how multiple motion-energy components are combined. Psychophysical
      data have been used to argue that motion-energy components representing opposite
      directions are subtracted from each other. Our data show, however, that the
      interactions among motion-energy components are more complex. In particular, we
      found that the influence of a given component on the response to a stimulus
      consisting of multiple components depends on factors other than the response to
      that component alone. This suggests that there are subthreshold nonlinear
      interactions among multiple motion-energy components; these could take place
      within MT or in earlier stages of the motion network such as V1. We propose a
      model that captures the complexity of these component interactions by means of a
      competitive interaction among the components. This provides a better description
      of the MT responses than the subtractive motion opponency envisaged in the motion
      energy model, even when the latter is combined with a gain-control mechanism. The
      competitive interaction extends the dynamic range of the cells and allows them to
      provide information on more subtle changes in motion patterns, including changes
      that are not purely directional.

PMID- 15574801
TI  - Interhemispheric coupling of corticospinal excitability is suppressed during
      voluntary muscle activation.
AB  - Motor-evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) show
      a trial-to-trial variation in size at rest that is positively correlated for
      muscles of the same, and opposite, upper limbs. To investigate the mechanisms
      responsible for this we have examined the effect of voluntary activation on the
      correlated fluctuations of MEP size. In 8 subjects TMS was concurrently applied
      to the motor cortex of each hemisphere using 2 figure-8 coils. MEPs (n = 50) were
      recorded from left and right first dorsal interosseous (FDI), abductor digiti
      minimi (ADM), and extensor digitorum communis. At rest, MEPs were significantly
      positively correlated for pairs of muscles of the same (75% of comparisons) and
      opposite limb (56% of comparisons). The correlation for within-limb muscle pairs
      was strongest for FDI and ADM. In contrast, between-limb MEP correlations showed
      no somatotopic organization. Voluntary activation reduced the strength of MEP
      correlations between limbs, even for muscle pairs that remained at rest while a
      remote upper limb muscle was active. In contrast, activation of a remote muscle
      did not affect the strength of MEP correlation for muscle pairs within the same
      limb that remained at rest. For within-limb comparisons, activation of one or
      both muscles of a pair reduced the strength of the MEP correlation, but to a
      lesser extent than for between-limb pairs. It is concluded that the process
      linking corticospinal excitability in the two hemispheres is suppressed during
      voluntary activation, and that different processes contribute to common
      fluctuations in MEP size for muscles within the same limb.

PMID- 15574802
TI  - The N-X-S/T consensus sequence is required but not sufficient for bacterial N
      linked protein glycosylation.
AB  - In the Gram-negative bacterium Campylobacter jejuni there is a pgl (protein
      glycosylation) locus-dependent general N-glycosylation system of proteins. One of
      the proteins encoded by pgl locus, PglB, a homolog of the eukaryotic
      oligosaccharyltransferase component Stt3p, is proposed to function as an
      oligosaccharyltransferase in this prokaryotic system. The sequence requirements
      of the acceptor polypeptide for N-glycosylation were analyzed by reverse genetics
      using the reconstituted glycosylation of the model protein AcrA in Escherichia
      coli. As in eukaryotes, the N-X-S/T sequon is an essential but not a sufficient
      determinant for N-linked protein glycosylation. This conclusion was supported by
      the analysis of a novel C. jejuni glycoprotein, HisJ. Export of the polypeptide
      to the periplasm was required for glycosylation. Our data support the hypothesis
      that eukaryotic and bacterial N-linked protein glycosylation are homologous
      processes.

PMID- 15574803
TI  - Inner core assembly and structure of the lipooligosaccharide of Neisseria
      meningitidis: capacity of strain NMB to express all known immunotype epitopes.
AB  - Neisseria meningitidis expresses a heterogeneous population of
      lipooligosaccharide (LOS) inner cores variously substituted with alpha1-3-linked
      glucose and O-3, O-6, and O-7 linked phosphoethanolamine (PEA), as well as
      glycine, attached to HepII. Combinations of these attachments to the LOS inner
      core represent immunodominant epitopes that are being exploited as future vaccine
      candidates. Historically, each LOS immunotype was structurally assessed and
      prescribed a certain unique inner core epitope. We report that a single isolate,
      strain NMB, possesses the capacity to produce all of the known neisserial LOS
      inner core immunotype structures. Analysis of the inner cores from parental LOS
      revealed the presence or absence of alpha1,3-linked glucose, O-6 and/or O-7
      linked PEA, in addition to glycine attached at the 7 position of the HepII inner
      core. Identification and inactivation of lpt-6 in strain NMB resulted in the loss
      of both O-6 and O-7 linked PEA groups from the LOS inner core, suggesting that
      Lpt-6 of strain NMB may have bifunctional transferase activities or that the O-6
      linked PEA groups once attached to the inner core undergo nonenzymatic transfer
      to the O-7 position of HepII. Although O-3 linked PEA was not detected in
      parental LOS inner cores devoid of alpha1-3-linked glucose residues, LOS
      glycoforms bearing O-3 PEA groups accumulated in a truncated mutant, NMBlgtK
      (Hep2Kdo2-lipid A). Because these structures disappeared upon inactivation of the
      lpt-3 locus, strain NMB expresses a functional O-3 PEA transferase. The LOS
      glycoforms expressed by NMBlgtK were also devoid of glycine attachments,
      indicating that glycine was added to the inner core after the completion of the
      gamma-chain by LgtK. In conclusion, strain NMB has the capability to express all
      known inner core structures, but in in vitro culture L2 and L4 immunotype
      structures are predominantly expressed.

PMID- 15574804
TI  - Recurrent recruitment of the THAP DNA-binding domain and molecular domestication
      of the P-transposable element.
AB  - The recently described THAP domain motif characterizes a DNA-binding domain (DBD)
      that is widely conserved in human and in animals. It presents a similarity with
      the DBD of the P element transposase of D. melanogaster. We show here that the P
      Drosophila neogenes derived from P-transposable elements conserve the THAP
      domain. Moreover, secondary rearrangements by exon shuffling indicate the
      recurrent recruitment of this domain by the host genome. As P sequences and THAP
      genes are found together in many animal genomes, we discuss the possibility that
      the THAP proteins have acquired their domain as a result of recurrent molecular
      domestication of P-transposable elements.

PMID- 15574805
TI  - Naturally occurring transposable elements disrupt hsp70 promoter function in
      Drosophila melanogaster.
AB  - Naturally occurring transposable element (TE) insertions that disrupt Drosophila
      promoters are correlated with modified promoter function and are posited to play
      a significant role in regulatory evolution, but their phenotypes have not been
      established directly. To establish the functional consequences of these TE
      insertions, we created constructs with either TE-bearing or TE-lacking hsp70
      promoters fused to a luciferase reporter gene and assayed luciferase luminescence
      in transiently transfected Drosophila cells. Each of the four TEs reduces
      luciferase signal after heat shock and heat inducibility of the hsp70 promoter.
      To test if the differences in hsp70 promoter activity are TE-sequence dependent,
      we replaced each of the TEs with multiple intergenic sequences of equal length.
      These replacement insertions similarly reduced luciferase signal, suggesting that
      the TEs affect hsp70 promoter function by altering promoter architecture. These
      results are consistent with differences in Hsp70 expression levels, inducible
      thermotolerance, and fecundity previously associated with the TEs. That two
      different varieties of TEs in two different hsp70 genes have common effects
      suggests that TE insertion represents a general mechanism through which selection
      manipulates hsp70 gene expression.

PMID- 15574806
TI  - Clusters of co-expressed genes in mammalian genomes are conserved by natural
      selection.
AB  - Genes that belong to the same functional pathways are often packaged into operons
      in prokaryotes. However, aside from examples in nematode genomes, this form of
      transcriptional regulation appears to be absent in eukaryotes. Nevertheless, a
      number of recent studies have shown that gene order in eukaryotic genomes is not
      completely random, and that genes with similar expression patterns tend to be
      clustered together. What remains unclear is whether co-expressed genes have been
      gathered together by natural selection to facilitate their regulation, or if the
      genes are co-expressed simply by virtue of their being close together in the
      genome. Here, we show that gene expression clusters tend to contain fewer
      chromosomal breakpoints between human and mouse than expected by chance, which
      indicates that they are being held together by natural selection. This conclusion
      applies to clusters defined on the basis of broad (housekeeping) expression, or
      on the basis of correlated transcription profiles across tissues. Contrary to
      previous reports, we find that genes with high expression are not clustered to a
      greater extent than expected by chance and are not conserved during evolution.

PMID- 15574807
TI  - Degenerative evolution and functional diversification of type-III secretion
      systems in the insect endosymbiont Sodalis glossinidius.
AB  - Sodalis glossinidius, a maternally transmitted endosymbiont of tsetse flies,
      maintains two phylogenetically distinct type-III secretion systems encoded by
      chromosomal symbiosis regions designated SSR-1 and SSR-2. Although both symbiosis
      regions are closely related to extant pathogenicity islands with similar gene
      inventories, SSR-2 has undergone novel degenerative adaptations in the transition
      to mutualism. Notably, SSR-2 lacks homologs of genes found in SSR-1 that encode
      secreted effector proteins known to facilitate the host cell cytoskeletal
      rearrangements necessary for bacterial entry and uptake into eukaryotic cells.
      Also, as a result of relaxed selection, SSR-2 has undergone inactivation of genes
      encoding components of the type-III secretion system needle substructure. In the
      current study, we used quantitative PCR to determine the expression profiles of
      ysaV (SSR-1) and invA (SSR-2) transcripts when S. glossinidius infects an insect
      cell line, and we used an invasion assay to characterize the phenotype of an S.
      glossinidius mutant that lacks the ability to produce an OrgA protein that is
      required for function of the SSR-2 secretome. Whereas SSR-1 is required for
      bacterial invasion of host cells and ysaV is expressed when bacteria contact host
      cells, SSR-2 is required for bacterial proliferation after entry, and invA is
      only expressed in the intracellular stage of infection. These results demonstrate
      that degenerative genetic adaptations in SSR-2 have promoted functional
      diversification of the Sodalis SSR-2 type-III secretion system.

PMID- 15574808
TI  - New regulatory regions of Drosophila 412 retrotransposable element generated by
      recombination.
AB  - There are no doubts that transposable elements (TEs) have greatly influenced
      genomes evolution. They have, however, evolved in different ways throughout
      mammals, plants, and invertebrates. In mammals they have been shown to be widely
      present but with low transposition activity; in plants they are responsible for
      large increases in genome size. In Drosophila, despite their low amount,
      transposition seems to be higher. Therefore, to understand how these elements
      have evolved in different genomes and how host genomes have proposed to go around
      them, are major questions on genome evolution. We analyzed sequences of the
      retrotransposable elements 412 in natural populations of the Drosophila simulans
      and D. melanogaster species that greatly differ in their amount of TEs. We
      identified new subfamilies of this element that were the result of mutation or
      insertion-deletion process, but also of interfamily recombinations. These new
      elements were well conserved in the D. simulans natural populations. The new
      regulatory regions produced by recombination could give rise to new elements able
      to overcome host control of transposition and, thus, become potential genome
      invaders.

PMID- 15574809
TI  - Fast adaptive coevolution of nuclear and mitochondrial subunits of ATP synthetase
      in orangutan.
AB  - Nuclear and mitochondrial genomes have to work in concert to generate a
      functional oxidative phosphorylation (OXPHOS) system. We have previously shown
      that we could restore partial OXPHOS function when chimpanzee or gorilla
      mitochondrial DNA (mtDNA) were introduced into human cells lacking mtDNA.
      However, we were unable to maintain orangutan mitochondrial DNA in a human cell.
      We have now produced chimpanzee, gorilla, orangutan, and baboon cells lacking
      mtDNA and attempted to introduce mtDNA from different apes into them.
      Surprisingly, we were able to maintain human mtDNA in an orangutan nuclear
      background, even though these cells showed severe OXPHOS abnormalities, including
      a complete absence of assembled ATP synthetase. Phylogenetic analysis of complex
      V mtDNA-encoded subunits showed that they are among the most evolutionarily
      divergent components of the mitochondrial genome between orangutan and the other
      apes. Our studies showed that adaptive coevolution of nuclear and mitochondrial
      components in apes can be fast and accelerate in recent branches of anthropoid
      primates.

PMID- 15574810
TI  - Sex-specific responses to urinary chemicals by the mouse vomeronasal organ.
AB  - Social behaviors of most mammals are affected by chemical signals, pheromones,
      exchanged between conspecifics. Previous experiments have shown that behavioral
      responses to the same pheromone differ depending on the sex and endocrine status
      of the respondent. Although the exact mechanism of this dimorphism is not known,
      one possible contributor may be due to sexually dimorphic receptors or due to
      differences in central processing within the brain. In order to investigate the
      differences in response between male and female mice to the same pheromonal
      stimulus two urinary compounds (2-heptanone and 2,5-dimethylpyrazine) were used
      to stimulate the production of Inositol (1,4,5)-trisphosphate (IP(3)) in
      microvillar membrane preparations of the vomeronasal organ as an indirect
      measurement of pheromonal stimulation. Incubation of such membranes from
      prepubertal mice with urine from the same sex or opposite sex, results in an
      increase in production of IP(3). This stimulation is mimicked by GTPgammaS and
      blocked by GDPbetaS. Furthermore we found that 2-heptanone present in both male
      and female urine was capable of stimulating increased production of IP(3) in the
      female VNO but not the male VNO. Finally, 2,5-dimethylpyrazine present only in
      female urine was also only capable of stimulating increased production of IP(3)
      in the female VNO.

PMID- 15574811
TI  - Transcellular and paracellular elements of salt chemosensation in toad skin.
AB  - Dehydrated toads absorb water by pressing a specialized (seat patch) area of the
      skin to moist surfaces. This behavior, the water absorption response (WR), is
      preceded by periods of more limited skin contact (seat patch down, SPD) in which
      the suitability of the rehydration source is evaluated. WR and SPD behaviors were
      suppressed on 250 mM NaCl and 200 mM KCl solutions. Ten micromolar amiloride
      partially restored SPD and WR on NaCl solutions. The addition of 5 mM La(3+) also
      partially restored the initiation of WR and this effect was additive to the
      effect of amiloride, suggesting transcellular and paracellular pathways exist in
      parallel. Similarly, 5 mM La(3+) partially restored the initiation of WR on KCl
      solutions, to levels comparable to those with K(+)gluconate, suggesting a
      paracellular pathway for detection of K(+). Hyperosmotic (250 mM) NaCl solutions
      bathing the mucosal surface rapidly and reversibly increased the paracellular
      conductance of isolated skin and this increase was partially inhibited by 5 mM
      La(3+). These results suggest that the regulation of tight junctions has a
      chemosensory role in toad skin.

PMID- 15574812
TI  - Experimental and numerical determination of odorant solubility in nasal and
      olfactory mucosa.
AB  - Odorant deposition in the nasal and olfactory mucosas is dependent on a number of
      factors including local air/odorant flow distribution patterns, odorant mucosal
      solubility and odorant diffusive transport in the mucosa. Although many of these
      factors are difficult to measure, mucosal solubility in the bullfrog mucus has
      been experimentally determined for a few odorants. In the present study an
      experimental procedure was combined with computational fluid dynamic (CFD)
      techniques to further describe some of the factors that govern odorant mucosal
      deposition. The fraction of odorant absorbed by the nasal mucosa (eta) was
      experimentally determined for a number of odorants by measuring the concentration
      drop between odorant 'blown' into one nostril and that exiting the contralateral
      nostril while the subject performed a velopharyngeal closure. Odorant
      concentrations were measured with a photoionization detector. Odorants were
      delivered to the nostrils at flow rates of 3.33 and 10 l/min. The velopharyngeal
      closure nasal air/odorant flows were then simulated using CFD techniques in a 3-D
      anatomically accurate human nose modeland the mucosal odorant uptake was
      numerically calculated. The comparison between the numerical simulations and the
      experimental results lead to an estimation of the human mucosal odorant
      solubility and the mucosal effective diffusive transport resistance. The results
      of the study suggest that the increase in diffusive resistance of the mucosal
      layer over that of a thin layer of water seemed to be general and non-odorant
      specific; however, the mucosa solubility was odorant specific and usually
      followed the trend that odorants with lower water solubility were more soluble in
      the mucosa than would be predicted from water solubility alone. The ability of
      this approach to model odorant movement in the nasal cavity was evaluated by
      comparison of the model output with known values of odorant mucosa solubility.

PMID- 15574813
TI  - The contribution of taste bud populations to bitter avoidance in mouse strains
      differentially sensitive to sucrose octa-acetate and quinine.
AB  - Mice of the SWR/J (SW) strain avoid orally delivered sucrose octa-acetate (SOA),
      whereas the mice of the C3HeB/FeJ (C3) strain are insensitive to SOA. Mice of
      both strains and of a congenic strain (C3.SW) that shares more than 99% of the C3
      genome, were tested in a taste-salient brief-access taste test for responses to
      SOA and quinine hydrochloride, before and after transection of the
      glossopharyngeal or chorda tympani nerve, or sham surgery. Prior to surgery,
      congenic SOA tasters (C3.SW(T)) were phenotypically identical to the SW strain in
      avoidance of SOA, but showed a greater reduction in sensitivity after nerve
      transection. For quinine avoidance, which is thought to be a polygenic trait, SW
      mice showed the greatest sensitivity to quinine, C3 the least and C3.SW(T) mice
      were different from both parental strains, showing intermediate sensitivity.
      Nerve transections had only a moderate effect on quinine sensitivity, suggesting
      that both anterior and posterior taste bud fields contribute to behavioral
      quinine avoidance. These findings are discussed with regard to the distribution
      in the oral cavity of putative taste receptors for quinine and SOA and the
      peripheral organization of bitter taste.

PMID- 15574814
TI  - Gustatory neural responses to umami taste stimuli in C57BL/6ByJ and 129P3/J mice.
AB  - In long-term two-bottle tests, mice from the C57BL/6ByJ (B6) strain drink more
      monosodium L-glutamate (MSG) and inosine-5'-monophosphate (IMP) compared with
      mice from the 129P3/J (129) strain. The goal of this study was to assess the role
      of afferent gustatory input in these strain differences. We measured integrated
      responses of the mouse chorda tympani and glossopharyngeal nerves to lingual
      application of compounds that evoke umami taste in humans: MSG, monoammonium L
      glutamate (NH(4) glutamate), IMP and guanosine-5'-monophosphate (GMP) and also to
      other taste stimuli. Chorda tympani responses to MSG and NH(4) glutamate were
      similar in B6 and 129 mice. Chorda tympani responses to IMP and GMP were lower in
      B6 than in 129 mice. Responses to umami stimuli in the glossopharyngeal nerve did
      not differ between the B6 and 129 strains. Responses to MSG, IMP and GMP were not
      affected by sodium present in these compounds because B6 and 129 mice had similar
      neural taste responses to NaCl. This study has demonstrated that the increased
      ingestive responses to the umami stimuli in B6 mice are accompanied by either
      unchanged or decreased neural responses to these stimuli. Lack of support for the
      role of the chorda tympani or glossopharyngeal nerves in the enhanced consumption
      of MSG and IMP by B6 mice suggests that it is due to some other factors. Although
      results of our previous study suggest that postingestive effects of MSG can
      affect its intake, contribution of other gustatory components (e.g. greater
      superficial petrosal nerve or central gustatory processing) to the strain
      differences in consumption of umami compounds also cannot be excluded. Strain
      differences in gustatory neural responses to nucleotides but not glutamate
      suggest that these compounds may activate distinct taste transduction mechanisms.

PMID- 15574815
TI  - Positive emotional priming of facial affect perception in females is diminished
      by chemosensory anxiety signals.
AB  - Chemosensory communication of anxiety is a common phenomenon in vertebrates and
      improves perceptual and responsive behaviour in the perceiver in order to
      optimize ontogenetic survival. A few rating studies reported a similar phenomenon
      in humans. Here, we investigated whether subliminal face perception changes in
      the context of chemosensory anxiety signals. Axillary sweat samples were taken
      from 12 males while they were waiting for an academic examination and while
      exercising ergometric training some days later. 16 subjects (eight females)
      participated in an emotional priming study, using happy, fearful and sad facial
      expressions as primes (11.7 ms) and neutral faces as targets (47 ms). The pooled
      chemosensory samples were presented before and during picture presentation (920
      ms). In the context of chemosensory stimuli derived from sweat samples taken
      during the sport condition, subjects judged the targets significantly more
      positive when they were primed by a happy face than when they were primed by the
      negative facial expressions (P = 0.02). In the context of the chemosensory
      anxiety signals, the priming effect of the happy faces was diminished in females
      (P = 0.02), but not in males. It is discussed whether, in socially relevant
      ambiguous perceptual conditions, chemosensory signals have a processing advantage
      and dominate visual signals or whether fear signals in general have a stronger
      behavioural impact than positive signals.

PMID- 15574816
TI  - Behavioral comparisons of the tastes of L-alanine and monosodium glutamate in
      rats.
AB  - Recent research has implicated T1R1/T1R3 as the primary taste receptor in mammals
      for detecting L-amino acids, including L-monosodium glutamate (MSG) and L
      alanine. Previous behavioral studies with rodents found only minimal evidence
      that these two substances share perceptual qualities, but those studies did not
      control for the taste of sodium associated with MSG. This study used several
      behavioral methods to compare the perceptual qualities of MSG and L-alanine in
      rats, using amiloride (a sodium channel blocker) to reduce the sodium component
      of MSG taste. Detection thresholds of L-alanine in rats ranged between 0.4 and
      2.5 mM, with or without amiloride added, which are similar to threshold estimates
      for MSG. Conditioned taste aversion (CTA) found that rats showed strong cross
      generalization of CTA between MSG and L-alanine when mixed with amiloride,
      indicating the two substances have similar perceptual qualities. Discrimination
      methods showed that rats easily discriminated between L-alanine and MSG unless
      the cue function of sodium was reduced. The discrimination became significantly
      more difficult at concentrations < 100 mM when amiloride was added to all stimuli
      and became even more difficult when NaCl was also added to L-alanine solutions to
      match the sodium concentrations of MSG. These results indicate that,
      perceptually, MSG and L-alanine have quite similar taste qualities and support
      the hypothesis that these two L-amino acids activate a common taste receptor. The
      differences in perceptual qualities also suggest separate afferent processing of
      one or both substances may also be involved.

PMID- 15574817
TI  - An odorant derivative as an antagonist for an olfactory receptor.
AB  - Different odorants are recognized by different combinations of G protein-coupled
      olfactory receptors, and thereby, odor identity is determined by a combinatorial
      receptor code for each odorant. We recently demonstrated that odorants appeared
      to compete for receptor sites to act as an agonist or an antagonist. Therefore,
      in natural circumstances where we always perceive a mixture of various odorants,
      olfactory receptor antagonism between odorants may result in a receptor code for
      the mixture that cannot be predicted from the codes for its individual
      components. Here we show that stored isoeugenol has an antagonistic effect on a
      mouse olfactory receptor, mOR-EG. However, freshly purified isoeugenol did not
      have an inhibitory effect. Instead, an isoeugenol derivative produced during
      storage turned out to be a potent competitive antagonist of mOR-EG. Structural
      analysis revealed that this derivative is an oxidatively dimerized isoeugenol
      that naturally occurs by oxidative reaction. The current study indicates that as
      odorants age, they decompose or react with other odorants, which in turn affects
      responsiveness of an olfactory receptor(s).

PMID- 15574818
TI  - A strong nerve dependence of sonic hedgehog expression in basal cells in mouse
      taste bud and an autonomous transcriptional control of genes in differentiated
      taste cells.
AB  - The nerve-dependency of gene expression in mouse taste bud was examined through
      an analysis of changes in gene expression in and around the taste buds in
      circumvallate papillae after surgery of cranial nerve IXth (glossopharyngeal
      nerve). The number of cells expressing T1r3, gustducin, Mash1 and Nkx2.2
      gradually decreased after denervation. However, the expression intensity of these
      genes was barely influenced by denervation, and strong expression was observed at
      6 days after denervation. In contrast, the basal cell-specific Sonic hedgehog
      (Shh) expression in the taste buds was decreased markedly at 6 h after
      denervation. In the regeneration process of taste buds, Shh expression was
      observed during a very early phase before taste bud formation. These results
      indicate the autonomous transcriptional control of genes in differentiated taste
      cells and the strong nerve-dependency of Shh expression in basal cells.
      Furthermore, in order to reveal the mitotic activity of Shh-expressing cells in
      taste buds, the BrdU-labeling experiments were performed using a combination of
      BrdU-immunohistochemistry and in situ hybridization. BrdU-signal was very rarely
      observed in Shh-expressing cells immediately after BrdU injection, and the
      signals were noted mainly in Ptc-expressing cells. BrdU signals rapidly increased
      in Shh-expressing cells in following 12 h and began to decrease after 2 days post
      injection. These results suggest that most Shh-expressing cells are not
      mitotically active, but that Shh-expressing cells may be in the early transient
      developmental state of taste cells in taste buds.

PMID- 15574819
TI  - Orientation behaviour of the blood-sucking bug triatoma infestans to short-chain
      fatty acids: synergistic effect of L-lactic acid and carbon dioxide.
AB  - The role of short-chain fatty acids in the host-seeking behaviour of Triatoma
      infestans larvae was investigated using a locomotion compensator. Several short
      chain fatty acids were tested alone over a wide range of doses, or in combination
      with L-lactic acid (L-LA; 100 microg). Bugs showed no attractive response to
      single carboxylic acids, but when L-LA was added to airstreams carrying specific
      intensities of either propionic (C3; 100 microg), butyric (C4; 1 microg) or
      valeric acid (C5; 1 microg), these mixtures elicited an attractive response,
      evincing a synergistic effect. No orientation response was observed when caproic
      acid (C6) was offered with L-LA at the doses tested. Two blends were created: (1)
      C3, C4 and C5 combined at the effective doses when added with L-LA [C3C4C5 (1)],
      and (2) C3, C4 and C5 combined at a third of those intensities [C3C4C5 (2)]. Both
      blends were tested alone, with L-LA (100 microg), with a sub-threshold
      concentration of CO(2) (300 p.p.m. above the ambient level), and combined with
      both compounds together. Oriented responses of bugs were only observed with the
      blend (2) added with L-LA and with the combination of this lure with CO(2). This
      last combination evoked a behavioural response similar in intensity to that
      induced by a live mouse.

PMID- 15574820
TI  - Reconstructing large regions of an ancestral mammalian genome in silico.
AB  - It is believed that most modern mammalian lineages arose from a series of rapid
      speciation events near the Cretaceous-Tertiary boundary. It is shown that such a
      phylogeny makes the common ancestral genome sequence an ideal target for
      reconstruction. Simulations suggest that with methods currently available, we can
      expect to get 98% of the bases correct in reconstructing megabase-scale
      euchromatic regions of an eutherian ancestral genome from the genomes of
      approximately 20 optimally chosen modern mammals. Using actual genomic sequences
      from 19 extant mammals, we reconstruct 1.1 Mb of ancient genome sequence around
      the CFTR locus. Detailed examination suggests the reconstruction is accurate and
      that it allows us to identify features in modern species, such as remnants of
      ancient transposon insertions, that were not identified by direct analysis.
      Tracing the predicted evolutionary history of the bases in the reconstructed
      region, estimates are made of the amount of DNA turnover due to insertion,
      deletion, and substitution in the different placental mammalian lineages since
      the common eutherian ancestor, showing considerable variation between lineages.
      In coming years, such reconstructions may help in identifying and understanding
      the genetic features common to eutherian mammals and may shed light on the
      evolution of human or primate-specific traits.

PMID- 15574821
TI  - The mouse genome: experimental examination of gene predictions and
      transcriptional start sites.
AB  - The completion of the mouse and other mammalian genome sequences will provide
      necessary, but not sufficient, knowledge for an understanding of much of mouse
      biology at the molecular level. As a requisite next step in this process, the
      genes in mouse and their structure must be elucidated. In particular, knowledge
      of the transcriptional start site of these genes will be necessary for further
      study of their regulatory regions. To assess the current state of mouse genome
      annotation to support this activity, we identified several hundred gene
      predictions in mouse with varying levels of supporting evidence and tested them
      using RACE-PCR. Modifications were made to the procedure allowing pooling of RNA
      samples, resulting in a scaleable procedure. The results illustrate potential
      errors or omissions in the current 5' end annotations in 58% of the genes
      detected. In testing experimentally unsupported gene predictions, we were able to
      identify 58 that are not usually annotated as genes but produced spliced
      transcripts (approximately 25% success rate). In addition, in many genes we were
      able to detect novel exons not predicted by any gene prediction algorithms. In
      19.8% of the genes detected in this study, multiple transcript species were
      observed. These data show an urgent need to provide direct experimental
      validation of gene annotations. Moreover, these results show that direct
      validation using RACE-PCR can be an important component of genome-wide
      validation. This approach can be a useful tool in the ongoing efforts to increase
      the quality of gene annotations, especially transcriptional start sites, in
      complex genomes.

PMID- 15574822
TI  - Long-range comparison of human and mouse Sprr loci to identify conserved
      noncoding sequences involved in coordinate regulation.
AB  - Mammalian epidermis provides a permeability barrier between an organism and its
      environment. Under homeostatic conditions, epidermal cells produce structural
      proteins, which are cross-linked in an orderly fashion to form a cornified
      envelope (CE). However, under genetic or environmental stress, specific genes are
      induced to rapidly build a temporary barrier. Small proline-rich (SPRR) proteins
      are the primary constituents of the CE. Under stress the entire family of 14 Sprr
      genes is upregulated. The Sprr genes are clustered within the larger epidermal
      differentiation complex on mouse chromosome 3, human chromosome 1q21. The
      clustering of the Sprr genes and their upregulation under stress suggest that
      these genes may be coordinately regulated. To identify enhancer elements that
      regulate this stress response activation of the Sprr locus, we utilized
      bioinformatic tools and classical biochemical dissection. Long-range comparative
      sequence analysis identified conserved noncoding sequences (CNSs). Clusters of
      epidermal-specific DNaseI-hypersensitive sites (HSs) mapped to specific CNSs.
      Increased prevalence of these HSs in barrier-deficient epidermis provides in vivo
      evidence of the regulation of the Sprr locus by these conserved sequences.
      Individual components of these HSs were cloned, and one was shown to have strong
      enhancer activity specific to conditions when the Sprr genes are coordinately
      upregulated.

PMID- 15574823
TI  - Contribution of Asian mouse subspecies Mus musculus molossinus to genomic
      constitution of strain C57BL/6J, as defined by BAC-end sequence-SNP analysis.
AB  - MSM/Ms is an inbred strain derived from the Japanese wild mouse, Mus musculus
      molossinus. It is believed that subspecies molossinus has contributed
      substantially to the genome constitution of common laboratory strains of mice,
      although the majority of their genome is derived from the west European M. m.
      domesticus. Information on the molossinus genome is thus essential not only for
      genetic studies involving molossinus but also for characterization of common
      laboratory strains. Here, we report the construction of an arrayed bacterial
      artificial chromosome (BAC) library from male MSM/Ms genomic DNA, covering
      approximately 1x genome equivalent. Both ends of 176,256 BAC clone inserts were
      sequenced, and 62,988 BAC-end sequence (BES) pairs were mapped onto the C57BL/6J
      genome (NCBI mouse Build 30), covering 2,228,164 kbp or 89% of the total genome.
      Taking advantage of the BES map data, we established a computer-based clone
      screening system. Comparison of the MSM/Ms and C57BL/6J sequences revealed
      489,200 candidate single nucleotide polymorphisms (SNPs) in 51,137,941 bp
      sequenced. The overall nucleotide substitution rate was as high as 0.0096. The
      distribution of SNPs along the C57BL/6J genome was not uniform: The majority of
      the genome showed a high SNP rate, and only 5.2% of the genome showed an
      extremely low SNP rate (percentage identity = 0.9997); these sequences are likely
      derived from the molossinus genome.

PMID- 15574824
TI  - Novel transcription regulatory elements in Caenorhabditis elegans muscle genes.
AB  - We report the identification of three new transcription regulatory elements that
      are associated with muscle gene expression in the nematode Caenorhabditis
      elegans. Starting from a subset of well-characterized nematode muscle genes, we
      identified conserved DNA motifs in the promoter regions using computational DNA
      pattern-recognition algorithms. These were considered to be putative muscle
      transcription regulatory motifs. Using the green-fluorescent protein (GFP) as a
      reporter, experiments were done to determine the biological activity of these
      motifs in driving muscle gene expression. Prediction accuracy of muscle
      expression based on the presence of these three motifs was encouraging; nine of
      10 previously uncharacterized genes that were predicted to have muscle expression
      were shown to be expressed either specifically or selectively in the muscle
      tissues, whereas only one of the nine that scored low for these motifs expressed
      in muscle. Knockouts of putative regulatory elements in the promoter of the mlc-2
      and unc-89 genes show that they significantly contribute to muscle expression and
      act in a synergistic manner. We find that these DNA motifs are also present in
      the muscle promoters of C. briggsae, indicating that they are functionally
      conserved in the nematodes.

PMID- 15574825
TI  - Computing prokaryotic gene ubiquity: rescuing the core from extinction.
AB  - The genomic core concept has found several uses in comparative and evolutionary
      genomics. Defined as the set of all genes common to (ubiquitous among) all
      genomes in a phylogenetically coherent group, core size decreases as the number
      and phylogenetic diversity of the relevant group increases. Here, we focus on
      methods for defining the size and composition of the core of all genes shared by
      sequenced genomes of prokaryotes (Bacteria and Archaea). There are few (almost
      certainly less than 50) genes shared by all of the 147 genomes compared, surely
      insufficient to conduct all essential functions. Sequencing and annotation errors
      are responsible for the apparent absence of some genes, while very limited but
      genuine disappearances (from just one or a few genomes) can account for several
      others. Core size will continue to decrease as more genome sequences appear,
      unless the requirement for ubiquity is relaxed. Such relaxation seems consistent
      with any reasonable biological purpose for seeking a core, but it renders the
      problem of definition more problematic. We propose an alternative approach (the
      phylogenetically balanced core), which preserves some of the biological utility
      of the core concept. Cores, however delimited, preferentially contain
      informational rather than operational genes; we present a new hypothesis for why
      this might be so.

PMID- 15574826
TI  - Marking of specific sequences in double-stranded DNA molecules--SNP detection and
      direct observation.
AB  - In this study, we describe a simple method to mark specific sequences in double
      stranded DNA molecules. For the marking, we used two specifically designed
      oligonucleotides, one of which is complementary to the sequence to be marked and
      the other, serving as a splint, to make the marking stable and detectable by
      subsequent various analytical means. In the presence of the two
      deoxyoligonucleotides, whereas RecA protein-mediated reaction converts the
      sequence to be marked to a regional triple-stranded structure with the
      complementary (probing) oligonucleotide, DNA ligase transforms it to a stable
      multi- (possibly quintuple) stranded structure with the splint oligonucleotide.
      The whole marking process is simple and completed in a single reaction mixture.
      Because RecA protein makes the marking to proceed with high fidelity, we were
      able to mark (detect) SNPs in complex genomes like human's. Furthermore, the
      structure of the marked sequence is stable and quite distinct enough to be
      readily detectable by biochemical means or direct observation by scanning probe
      microscopy.

PMID- 15574827
TI  - MicroRNA expression detected by oligonucleotide microarrays: system establishment
      and expression profiling in human tissues.
AB  - MicroRNAs (MIRs) are a novel group of conserved short approximately 22 nucleotide
      long RNAs with important roles in regulating gene expression. We have established
      a MIR-specific oligonucleotide microarray system that enables efficient analysis
      of the expression of the human MIRs identified so far. We show that the 60-mer
      oligonucleotide probes on the microarrays hybridize with labeled cRNA of MIRs,
      but not with their precursor hairpin RNAs, derived from amplified, size
      fractionated, total RNA of human origin. Signal intensity is related to the
      location of the MIR sequences within the 60-mer probes, with location at the 5'
      region giving the highest signals, and at the 3' end, giving the lowest signals.
      Accordingly, 60-mer probes harboring one MIR copy at the 5' end gave signals of
      similar intensity to probes containing two or three MIR copies. Mismatch analysis
      shows that mutations within the MIR sequence significantly reduce or eliminate
      the signal, suggesting that the observed signals faithfully reflect the abundance
      of matching MIRs in the labeled cRNA. Expression profiling of 150 MIRs in five
      human tissues and in HeLa cells revealed a good overall concordance with
      previously published results, but also with some differences. We present novel
      data on MIR expression in thymus, testes, and placenta, and have identified MIRs
      highly enriched in these tissues. Taken together, these results highlight the
      increased sensitivity of the DNA microarray over other methods for the detection
      and study of MIRs, and the immense potential in applying such microarrays for the
      study of MIRs in health and disease.

PMID- 15574828
TI  - High-throughput mutation detection underlying adaptive evolution of Escherichia
      coli-K12.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) analysis of base-specific cleavage products is an efficient,
      highly accurate tool for the detection of single base sequence variations. We
      describe the first application of this comparative sequencing strategy for
      automated high-throughput mutation detection in microbial genomes. The method was
      applied to identify DNA sequence changes that occurred in Escherichia coli K-12
      MG1655 during laboratory adaptive evolution to new optimal growth phenotypes.
      Experiments were based on a genome-scale in silico model of E. coli metabolism
      and growth. This model computes several phenotypic functions and predicts optimal
      growth rates. To identify mutations underlying a 40-d adaptive laboratory
      evolution on glycerol, we resequenced 4.4% of the E. coli-K12 MG1655 genome in
      several clones picked at the end of the evolutionary process. The 1.54-Mb screen
      was completed in 13.5 h. This resequencing study is the largest reported by MALDI
      TOF mass spectrometry to date. Ten mutations in 40 clones and three deviations
      from the reference sequence were detected. Mutations were predominantly found
      within the glycerol kinase gene. Functional characterization of the most
      prominent mutation shows its metabolic impact on the process of adaptive
      evolution. All sequence changes were independently confirmed by genotyping and
      Sanger-sequencing. We demonstrate that comparative sequencing by base-specific
      cleavage and MALDI-TOF mass spectrometry is an automated, fast, and highly
      accurate alternative to capillary sequencing.

PMID- 15574829
TI  - EAnnot: a genome annotation tool using experimental evidence.
AB  - The sequence of any genome becomes most useful for biological experimentation
      when a complete and accurate gene set is available. Gene prediction programs
      offer an efficient way to generate an automated gene set. Manual annotation, when
      performed by experienced annotators, is more accurate and complete than automated
      annotation. However, it is a laborious and expensive process, and by its nature,
      introduces a degree of variability not found with automated annotation. EAnnot
      (Electronic Annotation) is a program originally developed for manually annotating
      the human genome. It combines the latest bioinformatics tools to extract and
      analyze a wide range of publicly available data in order to achieve fast and
      reliable automatic gene prediction and annotation. EAnnot builds gene models
      based on mRNA, EST, and protein alignments to genomic sequence, attaches
      supporting evidence to the corresponding genes, identifies pseudogenes, and
      locates poly(A) sites and signals. Here, we compare manual annotation of human
      chromosome 6 with annotation performed by EAnnot in order to assess the latter's
      accuracy. EAnnot can readily be applied to manual annotation of other eukaryotic
      genomes and can be used to rapidly obtain an automated gene set.

PMID- 15574830
TI  - Arabidopsis plasma membrane proteomics identifies components of transport, signal
      transduction and membrane trafficking.
AB  - In order to identify integral proteins and peripheral proteins associated with
      the plasma membrane, highly purified Arabidopsis plasma membranes from green
      tissue (leaves and petioles) were analyzed by mass spectrometry. Plasma membranes
      were isolated by aqueous two-phase partitioning, which yields plasma membrane
      vesicles with a cytoplasmic-side-in orientation and with a purity of 95%. These
      vesicles were turned inside-out by treatment with Brij 58 to remove soluble
      contaminating proteins enclosed in the vesicles and to remove loosely bound
      contaminating proteins. In total, 238 putative plasma membrane proteins were
      identified, of which 114 are predicted to have transmembrane domains or to be
      glycosyl phosphatidylinositol anchored. About two-thirds of the identified
      integral proteins have not previously been shown to be plasma membrane proteins.
      Of the 238 identified proteins, 76% could be classified according to function.
      Major classes are proteins involved in transport (17%), signal transduction
      (16%), membrane trafficking (9%) and stress responses (9%). Almost a quarter of
      the proteins identified in the present study are functionally unclassified and
      more than half of these are predicted to be integral.

PMID- 15574831
TI  - Radial expansion of root cells and elongation of root hairs of Arabidopsis
      thaliana induced by massive doses of gamma irradiation.
AB  - Radial expansion of root cells and elongation of root hairs were induced within 3
      d of a massive dose (3 kGy) of gamma irradiation to Arabidopsis thaliana. Because
      treatment with the antioxidant n-propyl gallate before irradiation suppressed
      these changes, gamma irradiation partially rescued the rhd2 mutant (defective in
      NADPH oxidase); the superoxide-generating reagent paraquat induced similar root
      morphogenesis. These responses appeared to be induced by the active oxygen
      species (AOS) generated by water radiolysis. Ethylene production was induced
      immediately after gamma irradiation and reached a steady level after about 2 h.
      Addition of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid partly
      induced a similar expansion of root cells and elongation of root hairs. Addition
      of an inhibitor of ethylene biosynthesis, aminoethoxyvinylglycine, before gamma
      irradiation completely suppressed the formation of abnormal structures. These
      results suggest that the AOS is involved in the root morphological changes
      through the ethylene biosynthesis induced by gamma irradiation in Arabidopsis.

PMID- 15574832
TI  - Local induction of the alc gene switch in transgenic tobacco plants by
      acetaldehyde.
AB  - The alc promoter system, derived from the filamentous fungi Aspergillus nidulans,
      allows chemically regulated gene expression in plants and thereby the study of
      gene function as well as metabolic and developmental processes. In addition to
      ethanol, this system can be activated by acetaldehyde, described as the
      physiological inducer in A. nidulans. Here, we show that in contrast to ethanol,
      acetaldehyde allows tissue-specific activation of the alc promoter in transgenic
      tobacco plants. Soil drenching with aqueous acetaldehyde solutions at a
      concentration of 0.05% (v/v) resulted in the rapid and temporary induction of the
      alc gene expression system exclusively in roots. In addition, the split root
      system allows activation to be restricted to the treated part of the root. The
      temporary activation of the alc system by soil drenching with acetaldehyde could
      be prolonged over several weeks by subsequent applications at intervals of 7 d.
      This effect was demonstrated for the root-specific induction of a yeast-derived
      apoplast-located invertase under the control of the alcohol-inducible promoter
      system. In leaves, which exhibit a lower responsiveness to acetaldehyde than
      roots, the alc system was induced in the directly treated tissue only. Thus,
      acetaldehyde can be used as a local inducer of the alc gene expression system in
      tobacco plants.

PMID- 15574833
TI  - Induction of PR-1 accumulation accompanied by runaway cell death in the lsd1
      mutant of Arabidopsis is dependent on glutathione levels but independent of the
      redox state of glutathione.
AB  - The lesions simulating disease (lsd) mutants of Arabidopsis spontaneously develop
      hypersensitive-response-like lesions in the absence of pathogens. To address the
      function of the redox regulator glutathione in disease resistance, we examined
      the relationship between endogenous glutathione and PR-1 accumulation using one
      of these mutants, lsd1, as a disease resistance model. Lesion formation on lsd1
      was suppressed by weak light and initiated by the subsequent transition to normal
      light. The application of buthionine sulfoximine, a specific inhibitor of
      glutathione biosynthesis, suppressed conditionally induced runaway cell death and
      expression of the PR-1 gene, suggesting that glutathione regulates the
      conditional cell death and PR-1 gene expression. The application of reduced (GSH)
      or oxidized (GSSG) glutathione to lsd1 upregulated the level of total glutathione
      ([GSH]+[GSSG]) accompanied by hastened accumulation of PR-1, and the basal level
      of total glutathione in lsd1 was higher than that in wild-type plants. The
      glutathione redox state defined as [GSH]/([GSH]+[GSSG]) decreased following the
      conditional transition, but the suppression of this decrease by the application
      of GSH did not inhibit the accumulation of PR-1. Taken together, conditional PR-1
      accumulation in lsd1 is regulated not by the redox state but by the endogenous
      level of glutathione.

PMID- 15574834
TI  - Two distinct redox signaling pathways for cytosolic APX induction under
      photooxidative stress.
AB  - The cross-talk of two redox factors, H2O2 accumulation and redox status of
      photosynthetic electron transport (PET) in tobacco chloroplasts, on the
      expression of cytosolic ascorbate peroxidase (cAPX) was studied. Transgenic
      tobacco plants, which expressed respectively the Escherichia coli catalase and
      spinach thylakoid-membrane-bound APX in chloroplasts and showed increased
      tolerance to photooxidative stress, were used for evaluation of the relationship
      between H2O2 accumulation or change of redox status of PET and cAPX induction
      under photooxidative stress condition. There was no difference in the increase in
      the transcript level of cAPX in the first 1 h after irradiation with high
      intensity light between the wild-type and either of the transgenic plants. The
      transcript level of cAPX in the wild-type showed a steady gradual increase during
      the next 5 h, while that in the transgenic plants during this period was stable.
      The H2O2 level of wild-type plants increased after 1 h, while those of transgenic
      plants remained constant. The decrease in q(p) value in all types of plants
      occurred earlier than the increase in H2O2 level. These results indicate that the
      induction of cAPX expression is caused by a redox change in PET, probably through
      the plastquinone pool at an early stage and thereafter by an increase in the
      cellular H2O2 level.

PMID- 15574835
TI  - Photoinhibition of photosystem I at chilling temperature and subsequent recovery
      in Arabidopsis thaliana.
AB  - Chilling-induced photoinhibition and subsequent recovery was studied in
      Arabidopsis thaliana exposed to 4 degrees C and 150 micromol photons m(-2) s(-1).
      PSII showed progressive damage with a 14% decrease in quantum yield after 8 h
      exposure. In contrast, the damage to PSI leveled off after 8 h with a decrease in
      in vitro NADP+ photoreduction activity of around 32%. In vivo P700 measurements
      demonstrated that antenna efficiency was decreased by the photoinhibitory
      treatment. Measurements of P700 and immunoblotting demonstrated that the damaged
      PSI was not degraded during the 8 h light-chilling treatment, but after 12 h
      recovery at 20 degrees C, no damaged PSI remained in the thylakoids. Thus,
      degradation of damaged PSI is a step in the recovery and not a direct result of
      photodamage. Unlike photodamaged PSII, the PSI core complex is not repaired but
      completely degraded. In contrast, light harvesting complex I proteins have a slow
      turnover. PSII recovered completely within 8 h after transfer to 20 degrees C
      whereas PSI activity recovered very slowly, and the amount of PSI on a leaf area
      basis remained low even after 1 week at 20 degrees C. The results show that
      damage, protein turnover and recovery are well separated processes in
      Arabidopsis.

PMID- 15574836
TI  - Developmental expression of three mungbean Hsc70s and substrate-binding
      specificity of the encoded proteins.
AB  - We isolated three mungbean Hsc70 cDNAs (VrHsc70-1, 70-2 and 70-3) and
      characterized their developmental expression at both the transcript and protein
      levels. We also characterized the binding specificity between each VrHsc70
      protein and its potential substrates. RNase protection assays showed that these
      three cytosolic VrHsc70 genes were expressed similarly in all organs at all times
      during the mungbean life cycle, except at the initiation of germination and
      during late seed embryogenesis. Western blotting analyses showed that a different
      group of cytosolic VrHsc70 proteins accumulated in dehydrated seeds during seed
      maturation and the accumulated proteins remained high during the early stages of
      germination. Binding specificities of these three mungbean Hsc70s were determined
      using the C-terminal 30 kDa of the three VrHsc70s to select bound heptapeptides
      using phage display screening, and were confirmed by ELISA. We found that the
      heptapeptides, KVWVLPI, KLWVIPQ and YAPLSRL, specifically bound to the C-terminal
      30 kDa region of VrHsc70-1, 70-2 and 70-3, respectively. The hydrophobic residues
      in the core of the heptapeptides, as well as residues 6 and 7, might contribute
      to the binding specificity. Our results indicate that the function of these three
      VrHsc70s may not be important in seed maturation or in desiccation tolerance, but
      are more likely involved in normal growth and development.

PMID- 15574837
TI  - A systematic search for RNA editing sites in pea chloroplasts: an editing event
      causes diversification from the evolutionarily conserved amino acid sequence.
AB  - RNA editing in higher plant chloroplasts involves C-to-U conversion at specific
      sites in the transcripts. To examine whether pea shares editing sites with other
      angiosperms, a systematic search for editing sites in pea chloroplast transcripts
      was performed. Based on amino acid sequence alignment, 451 RNA editing sites were
      predicted from 60 transcripts. Sequence analysis of amplified cDNAs for these
      potential editing sites revealed 19 true editing sites from 13 transcripts.
      Together with those reported previously, the total number of editing sites is 27
      from 16 transcripts in pea chloroplasts. Twenty-two sites are conserved among
      other plant species, whereas five sites are unique to pea. Among the 27 editing
      sites, seven are partially edited. The most interesting is the ndhG site 1, which
      has led to the diversification of the evolutionarily conserved amino acid
      sequence. This observation suggests that some of the editing events cause the
      diversity of amino acid sequences, and hence, that prediction of editing sites
      based on amino acid sequence alignment has its own limitations.

PMID- 15574838
TI  - Inhibition of proteasome by MG-132 treatment causes extra phragmoplast formation
      and cortical microtubule disorganization during M/G1 transition in synchronized
      tobacco cells.
AB  - The 26S proteasome plays essential roles in cell cycle progression in various
      types of cell. We previously reported that the inhibition of 26S proteasome
      activities by a proteasome inhibitor, MG-132, exclusively caused cell cycle
      arrest in synchronized tobacco BY-2 cells. Here we report a further observation
      of 26S proteasome involvement during M/G1 transition utilizing a transgenetic BY
      2 cell line that stably expresses a GFP-alpha-tubulin fusion protein (BY-GT16).
      Interestingly, MG-132 treatment caused the arrest of cell cycle progression prior
      to entering the G1 phase. Indeed, phragmoplast-like structures were formed and
      cortical microtubules were not organized after the collapse of the original
      phragmoplasts. Additionally, actin microfilaments showed irregular rearrangements
      when further incubated with MG-132 and as the phragmoplast-like structures
      developed. Since these phragmoplast-like structures had a similar configuration
      and ability to form cell plates to that of the original phragmoplasts, we
      designated these phragmoplast-like structures as extra phragmoplasts.
      Furthermore, we showed that a tobacco kinesin-related polypeptide of 125 kDa
      (TKRP125) localized in the extra phragmoplasts and that its protein level
      remained unchanged during MG-132 treatment. We propose that TKRP125 might be one
      of the possible targets of the ubiquitin-proteasome degradation pathway during
      M/G1 transition.

PMID- 15574839
TI  - Identification of chloroplast signal recognition particle RNA genes.
AB  - The signal recognition particle (SRP) is a ribonucleoprotein complex responsible
      for targeting proteins to the ER membrane in eukaryotes, the plasma membrane in
      bacteria and the thylakoid membrane in chloroplasts. In higher plants two
      different SRP-dependent mechanisms have been identified: one post-translational
      for proteins imported to the chloroplast and one co-translational for proteins
      encoded by the plastid genome. The post-translational chloroplast SRP (cpSRP)
      consists of the protein subunits cpSRP54 and cpSRP43. An RNA component has not
      been identified and does not seem to be required for the post-translational
      cpSRP. The co-translational mechanism is known to involve cpSRP54, but an RNA
      component has not yet been identified. Several chloroplast genomes have been
      sequenced recently, making a phylogenetically broad computational search for
      cpSRP RNA possible. We have analysed chloroplast genomes from 27 organisms. In
      higher plant chloroplasts, no SRP RNA genes were identified. However, eight
      plastids from red algae and Chlorophyta were found to contain an SRP RNA gene.
      These results suggest that SRP RNA forms a complex in these plastids with
      cpSRP54, reminiscent of the eubacterial SRP.

PMID- 15574840
TI  - Biochemical background and compartmentalized functions of cytosolic glutamine
      synthetase for active ammonium assimilation in rice roots.
AB  - Rice plants in paddy fields prefer to utilize ammonium as a major nitrogen
      source. Glutamine synthetase (GS) serves for assimilation of ammonium in rice
      root, and ameliorates the toxic effect of ammonium excess. Among the three
      isoenzymes of the cytosolic GS1 gene family in rice, OsGLN1;1 and OsGLN1;2 were
      abundantly expressed in roots. Analysis of the purified enzymes showed that
      OsGLN1;1 and OsGLN1;2 can be classified into high-affinity subtypes with
      relatively high V(max) values, as compared with the major high-affinity
      isoenzyme, GLN1;1, in Arabidopsis. Low-affinity forms of GS1 comparable to those
      in Arabidopsis (GLN1;2 and GLN1;3) were absent in rice roots. The OsGLN1;1 and
      OsGLN1;2 transcripts showed reciprocal responses to ammonium supply in the
      surface cell layers of roots. OsGLN1;1 accumulated in dermatogen, epidermis and
      exodermis under nitrogen-limited condition. By contrast, OsGLN1;2 was abundantly
      expressed in the same cell layers under nitrogen-sufficient conditions,
      replenishing the loss of OsGLN1;1 following ammonium treatment. Within the
      central cylinder of elongating zone, OsGLN1;1 and OsGLN1;2 were both induced by
      ammonium, which was distinguishable from the response observed in the surface
      cell layers. The high-capacity Gln synthetic activities of OsGLN1;1 and OsGLN1;2
      facilitate active ammonium assimilation in specific cell types in rice roots.

PMID- 15574841
TI  - DNA interference: a simple and efficient gene-silencing system for high
      throughput functional analysis in the fern adiantum.
AB  - RNA interference (RNAi) has become a powerful tool for determining gene function
      and is used in a wide variety of organisms. Since it is necessary to generate
      double-stranded RNA (dsRNA) as an inducer for RNAi, preparation of RNAi-inducing
      constructs is somewhat cumbersome and time consuming, especially for the
      thousands of genes used in a genome-wide analysis. To overcome these problems, we
      have developed a more convenient gene-silencing method in the fern Adiantum using
      double-stranded DNA (dsDNA) as a model system for functional analysis in plants.
      Delivery of dsDNA fragments homologous to an endogenous gene into gametophytic
      cells can induce sequence-specific gene silencing. As it only requires dsDNA
      fragments homologous to a target gene, PCR-amplified fragments are enough to
      trigger gene silencing. Maximum gene silencing efficiencies of >90% have been
      achieved for transformed plants. In addition, simultaneous transfer of dsDNA
      fragments corresponding to multiple genes still has a silencing effect for
      individual genes. We term this approach 'DNA interference'.

PMID- 15574842
TI  - Isolation of putative glycoprotein gene from early somatic embryo of carrot and
      its possible involvement in somatic embryo development.
AB  - Somatic embryogenesis is a unique process in plant cells. For example,
      embryogenic cells (EC) of carrot (Daucus carota) maintained in a medium
      containing 2,4-dichlorophenoxyacetic acid (2,4-D) regenerate whole plants via
      somatic embryogenesis after the depletion of 2,4-D. Although some genes such as C
      ABI3 and C-LEC1 have been found to be involved in somatic embryogenesis, the
      critical molecular and cellular mechanisms for somatic embryogenesis are unknown.
      To characterize the early mechanism in the induction of somatic embryogenesis, we
      isolated genes expressed during the early stage of somatic embryogenesis after
      2,4-D depletion. Subtractive hybridization screening and subsequent RNA gel blot
      analysis suggested a candidate gene, Carrot Early Somatic Embryogenesis 1 (C
      ESE1). C-ESE1 encodes a protein that has agglutinin and S-locus-glycoprotein
      domains and its expression is highly specific to primordial cells of somatic
      embryo. Transgenic carrot cells with reduced expression of C-ESE1 had wide
      intercellular space and decreased polysaccharides on the cell surface and showed
      delayed development in somatic embryogenesis. The importance of cell-to-cell
      attachment in somatic embryogenesis is discussed.

PMID- 15574843
TI  - Pn-AMP1, a plant defense protein, induces actin depolarization in yeasts.
AB  - Pn-AMP1, Pharbitis nil antimicrobial peptide 1, is a small cysteine-rich peptide
      implicated in host-plant defense. We show here that Pn-AMP1 causes depolarization
      of the actin cytoskeleton in Saccharomyces cerevisiae and Candida albicans. Pn
      AMP1 induces rapid depolarization of actin cables and patches within 15 min.
      Increased osmolarity or temperature induces transient actin depolarization and
      results in increased sensitivity to Pn-AMP1, while cells conditioned to these
      stresses show less sensitivity. Mutations in components of a cell wall integrity
      pathway (Wsc1p, Rom2p, Bck1p and Mpk1p), which regulate actin repolarization,
      result in increased sensitivity to Pn-AMP1. A genetic screen reveals that
      mutations in components of the alpha-1,6-mannosyltransferase complex (Mnn10p,
      Mnn11p and Och1p), which regulate mannosylation of cell wall proteins, confer
      resistance to Pn-AMP1. FITC-conjugated Pn-AMP1 localizes to the outer surface of
      the cell with no significant staining observed in spheroplasts. Taken together,
      these results indicate that cell wall proteins are determinants of resistance to
      Pn-AMP1, and the ability of a plant defense protein to induce actin
      depolarization is important for its antifungal activity.

PMID- 15574844
TI  - Cadmium toxicity induced changes in nitrogen management in Lycopersicon
      esculentum leading to a metabolic safeguard through an amino acid storage
      strategy.
AB  - Tomato (Lycopersicon esculentum) seedlings were grown in the presence of cadmium.
      After 1 week of Cd treatment, a sharp decline in biomass accumulation in the
      leaves and roots was observed, together with a decrease in the rate of
      photosynthetic activity due to both Rubisco and chlorophyll degradation and
      stomata closure. Cadmium induced a significant decrease in nitrate content and
      inhibition of the activities of nitrate reductase, nitrite reductase, glutamine
      synthetase (GS) and ferredoxin-glutamate synthase. An increase in NADH-glutamate
      synthase and NADH-glutamate dehydrogenase activity was observed in parallel. The
      accumulation of ammonium into the tissues of treated plants was accompanied by a
      loss of total protein and the accumulation of amino acids. Gln represented the
      major amino acid transported through xylem sap of Cd-treated and control plants.
      Cadmium treatment increased the total amino acid content in the phloem,
      maintaining Gln/Glu ratios. Western and Northern blot analysis of Cd-treated
      plants showed a decrease in chloroplastic GS protein and mRNA and an increase in
      cytosolic GS and glutamate dehydrogenase transcripts and proteins. An increase in
      asparagine synthetase mRNA was observed in roots, in parallel with a strong
      increase in asparagine. Taken together, these results suggest that the plant
      response to Cd stress involved newly induced enzymes dedicated to coordinated
      leaf nitrogen remobilization and root nitrogen storage.

PMID- 15574845
TI  - Comparative studies on the Arabidopsis aldehyde oxidase (AAO) gene family
      revealed a major role of AAO3 in ABA biosynthesis in seeds.
AB  - The Arabidopsis aldehyde oxidase 3 (AAO3) gene encodes an enzyme that catalyzes
      the final step of ABA biosynthesis. AAO3 has been shown to be the major AAO
      involved in ABA biosynthesis in leaves under stress conditions. On the other
      hand, less severe phenotypes of the aao3 seeds suggested that other AAO(s) might
      also be involved in ABA biosynthesis in seeds. Among four AAOs (AAO1-AAO4), AAO1
      and AAO4 were the AAO expressed most abundantly in dry seeds and developing
      siliques, respectively. Unlike aao3, single loss-of-function mutants for AAO1 and
      AAO4 (aao1 and aao4), failed to show significant changes in endogenous ABA levels
      in seeds when compared with wild type. While aao3 seed germination was resistant
      to the gibberellin biosynthesis inhibitor, uniconazole, aao1 and aao4 showed no
      resistance and were similar to wild type. These results indicate that AAO3, but
      not AAO1 or AAO4, plays an important role in ABA biosynthesis in seeds. Mutations
      of AAO1 or AAO4 in the aao3 mutant background enhanced ABA deficiency in seeds,
      demonstrating that both gene products contribute partially to ABA biosynthesis in
      the aao3 mutant background. However, considering the enzymatic characters of AAO1
      and AAO4, their involvement in ABA biosynthesis in wild-type seeds may be
      negligible. We have concluded that AAO3 is the AAO that plays a major role in ABA
      biosynthesis in Arabidopsis seeds as well as in leaves.

PMID- 15574846
TI  - A mechanosensitive anion channel in Arabidopsis thaliana mesophyll cells.
AB  - Mechanosensitive ion channels are expected to play important roles in transducing
      mechanical stimuli into intracellular signals during the development and
      morphogenesis of higher plants. We have identified a novel mechanosensitive anion
      channel in the protoplast of Arabidopsis thaliana mesophyll cells by using the
      patch-clamp technique. The channel in the outside-out patches could be activated
      by positive pressure in the pipette while negative pressure had no effect. The
      amphipathic membrane crenator trinitrophenol, which is supposed to preferentially
      insert in the outer leaflet of the lipid bilayer of the plasma membrane,
      synergized with mechanical membrane stretch to activate the channel. These
      results suggest that the channel activation is mediated by a convex curvature of
      the plasma membrane. Therefore, activation of this channel may play an important
      role when cell volume is increasing during cell growth or hypo-osmotic challenge,
      which is accompanied by membrane stretch with increasingly convex curvature.

PMID- 15574847
TI  - The blue light-specific response of Vicia faba stomata acclimates to growth
      environment.
AB  - Stomata in epidermal strips from growth chamber-grown Vicia faba leaves opened
      less in response to white light than did stomata from greenhouse-grown leaves.
      Chlorophyll-mediated, red light-stimulated opening was similar in stomata from
      the two growth conditions, but stomata from the growth chamber environment had a
      severely reduced response to blue light. Transfer of plants between the two
      growth conditions resulted in an acclimation of the stomatal blue light response.
      Stomata lost blue light sensitivity within 1 d of transfer to growth chamber
      conditions and gained sensitivity to blue light over an 8 d period after transfer
      to a greenhouse. Short-term transfer experiments confirmed that the rapid loss of
      blue light sensitivity was an acclimation response, requiring between 12 and 20 h
      exposure to growth chamber conditions. The acclimation of the stomatal response
      to blue light was inversely related to a previously reported acclimation response
      in which stomata change between high CO2 sensitivity under growth chamber
      conditions and low CO2 sensitivity under greenhouse conditions. The time courses
      of the blue light and CO2 acclimation responses were virtually identical,
      suggesting the possibility of a common acclimation mechanism.

PMID- 15574848
TI  - Ectopic expression of the NtSET1 histone methyltransferase inhibits cell
      expansion, and affects cell division and differentiation in tobacco plants.
AB  - The tobacco NtSET1 gene encodes a member of the SUV39H family of histone
      methyltransferases. Ectopic expression of NtSET1 causes an increase in methylated
      histone H3 lysine 9 and abnormal chromosome segregation in tobacco suspension
      cells, and inhibits tobacco plant growth. Here we show that the inhibition of
      plant growth was caused by reduced cell expansion as well as by abnormal cell
      division and differentiation. We found that deletion of the C-terminally located
      catalytic domain of the protein abolished the ectopic effects of NtSET1 on plant
      growth. Our results indicate that histone H3 lysine 9 methylation is a critical
      mark of epigenetic control for plant development.

PMID- 15574849
TI  - Molecular and biochemical characterization of three WD-repeat-domain-containing
      inositol polyphosphate 5-phosphatases in Arabidopsis thaliana.
AB  - Type II inositol polyphosphate 5-phosphatases (5PTases) in animals and yeast have
      been known to be important for regulating inositol and phospholipid signaling by
      hydrolyzing phosphate from both inositol polyphosphates and phosphoinositides.
      However, the molecular and biochemical properties of type II 5PTases in plants
      have not yet been studied. In this report, we show that three Arabidopsis genes,
      At5PTase12, At5PTase13 and At5PTase14, encode proteins with a 5PTase domain and a
      WD-repeat domain, a novel combination present only in plant 5PTases. We
      demonstrate that these genes are differentially expressed in Arabidopsis organs
      and At5PTase13 is induced in response to ABA and wounding treatments. Our
      biochemical studies reveal that although both At5PTase12 and At5PTase13 exhibit
      phosphatase activity toward only Ins(1,4,5)P3, At5PTase14 hydrolyzes phosphate
      from PI(4,5)P2, PI(3,4,5)P3 and Ins(1,4,5)P3 with the highest substrate affinity
      toward PI(4,5)P2. All three At5PTases require Mg2+ for their phosphatase
      activities. Our molecular and biochemical characterization of three WD-repeat
      domain-containing At5PTases provides a foundation for further elucidation of
      their cellular functions in Arabidopsis.

PMID- 15574850
TI  - Symbiogenesis.

PMID- 15574851
TI  - Human endogenous retroviruses in health and disease: a symbiotic perspective.

PMID- 15574852
TI  - Clinical implications of ST-segment non-resolution after thrombolysis for
      myocardial infarction.
AB  - Failed reperfusion after thrombolytic therapy for acute myocardial infarction is
      common and signifies a poor prognosis. We investigated the clinical consequences
      of non-resolution of the ST segment after thrombolytic therapy for acute ST
      elevation myocardial infarction, in 85 consecutive patients admitted to a
      coronary care unit lacking rapid access to angioplasty. Failed thrombolysis was
      defined as <50% ST-segment resolution 180 minutes after the start of thrombolytic
      treatment. Outcomes were measured in terms of in-hospital adverse events, length
      of hospital stay, and mortality at 6 weeks and 1 year. Thrombolysis was
      successful, in terms of ST-segment resolution, in 45 patients (53%). After
      adjustment for other factors, ST resolution was the only independent predictor of
      an uncomplicated recovery in hospital (odds ratio 6.8, 95% confidence interval
      2.3 to 19.9; P<0.001). At 6 weeks and 1 year, overall mortality was lower in the
      ST resolution group, though these differences became non-significant on
      multivariate analysis. In patients who survived to hospital discharge, median
      length of stay was greater in successfully thrombolysed patients (9 days versus 8
      days) despite their lower rate of complications. ST-segment resolution is a
      useful marker of successful thrombolysis and relates to clinical outcome. If
      assessed routinely it might assist, along with other clinical markers, in the
      identification of low-risk patients who can be discharged early.

PMID- 15574853
TI  - Incidence of fatigue symptoms and diagnoses presenting in UK primary care from
      1990 to 2001.
AB  - Little is known about whether the incidence of symptoms of fatigue presented in
      primary care, and the consequent diagnoses made, change over time. The UK General
      Practice Research Database was used to investigate the annual incidence of both
      fatigue symptoms and diagnoses recorded in UK primary care from 1990 to 2001. The
      overall incidence of all fatigue diagnoses decreased from 87 per 100 000 patients
      in 1990 to 49 in 2001, a reduction of 44%, while postviral fatigue syndromes
      decreased from 81% of all fatigue diagnoses in 1990 to 60% in 2001. Chronic
      fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) together increased from
      9% to 26% of all fatigue diagnoses. The incidence of fibromyalgia increased from
      less than 1 per 100 000 to 35 per 100 000. In contrast, there was no consistent
      change in the incidence of all recorded symptoms of fatigue, with an average of
      1503 per 100 000, equivalent to 1.5% per year. CFS/ME and fibromyalgia were
      rarely diagnosed in children and were uncommon in the elderly. All symptoms and
      diagnoses were more common in females than in males. The overall incidence of
      fatigue diagnoses in general has fallen, but the incidence rates of the specific
      diagnoses of CFS/ME and fibromyalgia have risen, against a background of little
      change in symptom reporting. This is likely to reflect fashions in diagnostic
      labelling rather than true changes in incidence.

PMID- 15574854
TI  - Sham procedures and the ethics of clinical trials.

PMID- 15574855
TI  - Health policy and race equality: an illusion of progress?

PMID- 15574856
TI  - Pneumococcal sepsis: should we look for asplenia?

PMID- 15574857
TI  - Pseudophaeochromocytoma in two young Africans.

PMID- 15574858
TI  - Chemical meningitis due to rupture of a craniopharyngioma cyst.

PMID- 15574859
TI  - Inguinal lumps misidentified as ectopic testis.

PMID- 15574860
TI  - Severe salicylate poisoning treated conservatively.

PMID- 15574861
TI  - Recurrent laryngeal nerve palsy, dysphagia and aortic fistula.

PMID- 15574862
TI  - John Horder.

PMID- 15574863
TI  - One hundred years of barbiturates and their saint.

PMID- 15574864
TI  - William Close (1775-1813): medicine, music, ink and engines in the Lake District.

PMID- 15574866
TI  - Textbook of tropical surgery.

PMID- 15574865
TI  - The sickly Stuarts.

PMID- 15574867
TI  - Achilles tendinopathy.

PMID- 15574868
TI  - The surgeon's job.

PMID- 15574869
TI  - Adult bone-marrow stem cells.

PMID- 15574870
TI  - Coxibs and serious adverse cardiovascular events: a class-effect?

PMID- 15574871
TI  - Diathermy and tonsillectomy: criticism of NICE.

PMID- 15574872
TI  - Referral criteria in early rheumatoid arthritis.

PMID- 15574873
TI  - Compulsory helmets for cyclists.

PMID- 15574874
TI  - Dynamics of relative chromosome position during the cell cycle.
AB  - The position of chromosomal neighborhoods in living cells was followed using
      three different methods for marking chromosomal domains occupying arbitrary
      locations in the nucleus; photobleaching of GFP-labeled histone H2B, local UV
      marked DNA, and photobleaching of fluorescently labeled DNA. All methods revealed
      that global chromosomal organization can be reestablished through one cell
      division from mother to daughters. By simultaneously monitoring cell cycle stage
      in the cells in which relative chromosomal domain positions were tracked, we
      observed that chromosomal neighborhood organization is apparently lost in the
      early G1 phase of the cell cycle. However, the daughter cells eventually regain
      the general chromosomal organization pattern of their mothers, suggesting an
      active mechanism could be at play to reestablish chromosomal neighborhoods.

PMID- 15574875
TI  - Interaction of Sla2p's ANTH domain with PtdIns(4,5)P2 is important for actin
      dependent endocytic internalization.
AB  - A variety of studies have implicated the lipid PtdIns(4,5)P2 in endocytic
      internalization, but how this lipid mediates its effects is not known. The AP180
      N-terminal homology (ANTH) domain is a PtdIns(4,5)P2-binding module found in
      several proteins that participate in receptor-mediated endocytosis. One such
      protein is yeast Sla2p, a highly conserved actin-binding protein essential for
      actin organization and endocytic internalization. To better understand how
      PtdIns(4,5)P2 binding regulates actin-dependent endocytosis, we investigated the
      functions of Sla2p's ANTH domain. A liposome-binding assay revealed that Sla2p
      binds to PtdIns(4,5)P2 specifically through its ANTH domain and identified
      specific lysine residues required for this interaction. Mutants of Sla2p
      deficient in PtdIns(4,5)P2 binding showed significant defects in cell growth,
      actin organization, and endocytic internalization. These defects could be rescued
      by increasing PtdIns(4,5)P2 levels in vivo. Strikingly, mutant Sla2p defective in
      PtdIns(4,5)P2 binding localized with the endocytic machinery at the cell cortex,
      establishing that the ANTH-PtdIns(4,5)P2 interaction is not necessary for this
      association. In contrast, multicolor real-time fluorescence microscopy and
      particle-tracking analysis demonstrated that PtdIns(4,5)P2 binding is required
      during endocytic internalization. These results demonstrate that the interaction
      of Sla2p's ANTH domain with PtdIns(4,5)P2 plays a key role in regulation of the
      dynamics of actin-dependent endocytic internalization.

PMID- 15574876
TI  - Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies
      components in a Golgi-specific Ypt31/rab-GTPase signaling pathway.
AB  - Phosphorylated derivatives of phosphatidylinositol are essential regulators of
      both endocytic and exocytic trafficking in eukaryotic cells. In Saccharomyces
      cerevisiae, the phosphatidylinositol 4-kinase, Pik1p generates a distinct pool of
      PtdIns(4)P that is required for normal Golgi structure and secretory function.
      Here, we utilize a synthetic genetic array analysis of a conditional pik1 mutant
      to identify candidate components of the Pik1p/PtdIns(4)P signaling pathway at the
      Golgi. Our data suggest a mechanistic involvement for Pik1p with a specific
      subset of Golgi-associated proteins, including the Ypt31p rab-GTPase and the
      TRAPPII protein complex, to regulate protein trafficking through the secretory
      pathway. We further demonstrate that TRAPPII specifically functions in a Ypt31p
      dependent pathway and identify Gyp2p as the first biologically relevant GTPase
      activating protein for Ypt31p. We propose that multiple stage-specific signals,
      which may include Pik1p/PtdIns(4)P, TRAPPII and Gyp2p, impinge upon Ypt31
      signaling to regulate Golgi secretory function.

PMID- 15574877
TI  - Laminin-5 induces osteogenic gene expression in human mesenchymal stem cells
      through an ERK-dependent pathway.
AB  - The laminin family of proteins is critical for managing a variety of cellular
      activities including migration, adhesion, and differentiation. In bone, the roles
      of laminins in controlling osteogenic differentiation of human mesenchymal stem
      cells (hMSC) are unknown. We report here that laminin-5 is found in bone and
      expressed by hMSC. hMSC isolated from bone synthesize laminin-5 and adhere to
      exogenous laminin-5 through alpha3beta1 integrin. Adhesion to laminin-5 activates
      extracellular signal-related kinase (ERK) within 30 min and leads to
      phosphorylation of the osteogenic transcription factor Runx2/CBFA-1 within 8 d.
      Cells plated on laminin-5 for 16 d express increased levels of osteogenic marker
      genes, and those plated for 21 d deposit a mineralized matrix, indicative of
      osteogenic differentiation. Addition of the ERK inhibitor PD98059 mitigates these
      effects. We conclude that contact with laminin-5 is sufficient to activate ERK
      and to stimulate osteogenic differentiation in hMSC.

PMID- 15574878
TI  - Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by
      Delta1 and Jagged1.
AB  - Fringe O-fucose-beta1,3-N-acetylglucosaminyltransferases modulate Notch signaling
      by potentiating signaling induced by Delta-like ligands, while inhibiting
      signaling induced by Serrate/Jagged1 ligands. Based on binding studies, the
      differential effects of Drosophila fringe (DFng) on Notch signaling are thought
      to result from alterations in Notch glycosylation that enhance binding of Delta
      to Notch but reduce Serrate binding. Here, we report that expression of mammalian
      fringe proteins (Lunatic [LFng], Manic [MFng], or Radical [RFng] Fringe)
      increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3
      cells. Although Jagged1-induced signaling was suppressed by LFng and MFng, RFng
      enhanced signaling induced by either Delta1 or Jagged1, underscoring the
      diversity of mammalian fringe glycosyltransferases in regulating signaling
      downstream of different ligand-receptor combinations. Interestingly, suppression
      of Jagged1-induced Notch1 signaling did not correlate with changes in Jagged1
      binding as found for Delta1. Our data support the idea that fringe glycosylation
      increases Delta1 binding to potentiate signaling, but we propose that although
      fringe glycosylation does not reduce Jagged1 binding to Notch1, the resultant
      ligand-receptor interactions do not effectively promote Notch1 proteolysis
      required for activation of downstream signaling events.

PMID- 15574879
TI  - Cdc42 and RhoB activation are required for mannose receptor-mediated phagocytosis
      by human alveolar macrophages.
AB  - Human alveolar macrophages (AMs) phagocytose Pneumocystis (Pc) organisms
      predominantly through mannose receptors, although the molecular mechanism
      mediating this opsonin-independent process is not known. In this study, using AMs
      from healthy individuals, Pc phagocytosis was associated with focal F-actin
      polymerization and Cdc42, Rac1, and Rho activation in a time-dependent manner.
      Phagocytosis was primarily dependent on Cdc42 and RhoB activation (as determined
      by AM transfection with Cdc42 and RhoB dominant-negative alleles) and mediated
      predominantly through mannose receptors (as determined by siRNA gene silencing of
      AM mannose receptors). Pc also promoted PAK-1 phosphorylation, which was also
      dependent on RhoGTPase activation. HIV infection of AMs (as a model for reduced
      mannose receptor expression and function) was associated with impaired F-actin
      polymerization, reduced Cdc42 and Rho activation, and markedly reduced PAK-1
      phosphorylation in response to Pc organisms. In healthy AMs, Pc phagocytosis was
      partially dependent on PAK activation, but dependent on the Rho effector molecule
      ROCK. These data provide a molecular mechanism for AM mannose receptor-mediated
      phagocytosis of unopsonized Pc organisms that appears distinct from opsonin
      dependent phagocytic receptors. Reduced AM mannose receptor-mediated Cdc42 and
      Rho activation in the context of HIV infection may represent a mechanism that
      contributes to the pathogenesis of opportunistic pneumonia.

PMID- 15574880
TI  - Constitutively active G protein-coupled receptor mutants block dictyostelium
      development.
AB  - cAR1, a G protein-coupled receptor (GPCR) for cAMP, is required for the
      multicellular development of Dictyostelium. The activation of multiple pathways
      by cAR1 is transient because of poorly defined adaptation mechanisms. To
      investigate this, we used a genetic screen for impaired development to isolate
      four dominant-negative cAR1 mutants, designated DN1-4. The mutant receptors
      inhibit multiple cAR1-mediated responses known to undergo adaptation. Reduced in
      vitro adenylyl cyclase activation by GTPgammaS suggests that they cause
      constitutive adaptation of this and perhaps other pathways. In addition, the DN
      mutants are constitutively phosphorylated, which normally requires cAMP binding
      and possess cAMP affinities that are approximately 100-fold higher than that of
      wild-type cAR1. Two independent activating mutations, L100H and I104N, were
      identified. These residues occupy adjacent positions near the cytoplasmic end of
      the receptor's third transmembrane helix and correspond to the (E/D)RY motif of
      numerous mammalian GPCRs, which is believed to regulate their activation. Taken
      together, these findings suggest that the DN mutants are constitutively activated
      and block development by turning on natural adaptation mechanisms.

PMID- 15574881
TI  - Beta1-integrin orients epithelial polarity via Rac1 and laminin.
AB  - Epithelial cells polarize and orient polarity in response to cell-cell and cell
      matrix adhesion. Although there has been much recent progress in understanding
      the general polarizing machinery of epithelia, it is largely unclear how this
      machinery is controlled by the extracellular environment. To explore the signals
      from cell-matrix interactions that control orientation of cell polarity, we have
      used three-dimensional culture systems in which Madin-Darby canine kidney (MDCK)
      cells form polarized, lumen-containing structures. We show that interaction of
      collagen I with apical beta1-integrins after collagen overlay of a polarized MDCK
      monolayer induces activation of Rac1, which is required for collagen overlay
      induced tubulocyst formation. Cysts, comprised of a monolayer enclosing a central
      lumen, form after embedding single cells in collagen. In those cultures, addition
      of a beta1-integrin function-blocking antibody to the collagen matrix gives rise
      to cysts that have defects in the organization of laminin into the basement
      membrane and have inverted polarity. Normal polarity is restored by either
      expression of activated Rac1, or the inclusion of excess laminin-1 (LN-1).
      Together, our results suggest a signaling pathway in which the activation of
      beta1-integrins orients the apical pole of polarized cysts via a mechanism that
      requires Rac1 activation and laminin organization into the basement membrane.

PMID- 15574882
TI  - An internal motor kinesin is associated with the Golgi apparatus and plays a role
      in trichome morphogenesis in Arabidopsis.
AB  - Members of the kinesin superfamily are microtubule-based motor proteins that
      transport molecules/organelles along microtubules. We have identified similar
      internal motor kinesins, Kinesin-13A, from the cotton Gossypium hirsutum and
      Arabidopsis thaliana. Their motor domains share high degree of similarity with
      those of internal motor kinesins of animals and protists in the MCAK/Kinesin13
      subfamily. However, no significant sequence similarities were detected in
      sequences outside the motor domain. In Arabidopsis plants carrying the T-DNA
      knockout kinesin-13a-1 and kinesin-13a-2 mutations at the Kinesin-13A locus, >70%
      leaf trichomes had four branches, whereas wild-type trichomes had three.
      Immunofluorescent results showed that AtKinesin-13A and GhKinesin-13A localized
      to entire Golgi stacks. In both wild-type and kinesin-13a mutant cells, the Golgi
      stacks were frequently associated with microtubules and with actin
      microfilaments. Aggregation/clustering of Golgi stacks was often observed in the
      kinesin-13a mutant trichomes and other epidermal cells. This suggested that the
      distribution of the Golgi apparatus in cell cortex might require microtubules and
      Kinesin-13A, and the organization of Golgi stacks could play a regulatory role in
      trichome morphogenesis. Our results also indicate that plant kinesins in the
      MCAK/Kinesin-13 subfamily have evolved to take on different tasks than their
      animal counterparts.

PMID- 15574883
TI  - Transcriptional networks and cellular senescence in human mammary fibroblasts.
AB  - Senescence, the molecular program that limits the finite proliferative potential
      of a cell, acts as an important barrier to protect the body from cancer.
      Techniques for measuring transcriptome changes and for modulating their
      expression suggest that it may be possible to dissect the transcriptional
      networks underlying complex cellular processes. HMF3A cells are conditionally
      immortalized human mammary fibroblasts that can be induced to undergo coordinated
      senescence. Here, we used these cells in conjunction with microarrays, RNA
      interference, and in silico promoter analysis to promote the dissection of the
      transcriptional networks responsible for regulating cellular senescence. We first
      identified changes in the transcriptome when HMF3A cells undergo senescence and
      then compared them with those observed upon replicative senescence in primary
      human mammary fibroblasts. In addition to DUSP1 and known p53 and E2F targets, a
      number of genes such as PHLDA1, NR4A3, and a novel splice variant of STAC were
      implicated in senescence. Their role in senescence was then analyzed by RNA
      silencing followed by microarray analysis. In silico promoter analysis of all
      differential genes predicted that nuclear factor-kappaB and C/EBP transcription
      factors are activated upon senescence, and we confirmed this by electrophoretic
      mobility shift assay. The results suggest a putative signaling network for
      cellular senescence.

PMID- 15574884
TI  - Phosphorylation-regulated nucleocytoplasmic trafficking of internalized
      fibroblast growth factor-1.
AB  - Fibroblast growth factor-1 (FGF-1), which stimulates cell growth,
      differentiation, and migration, is capable of crossing cellular membranes to
      reach the cytosol and the nucleus in cells containing specific FGF receptors. The
      cell entry process can be monitored by phosphorylation of the translocated FGF-1.
      We present evidence that phosphorylation of FGF-1 occurs in the nucleus by
      protein kinase C (PKC)delta. The phosphorylated FGF-1 is subsequently exported to
      the cytosol. A mutant growth factor where serine at the phosphorylation site is
      exchanged with glutamic acid, to mimic phosphorylated FGF-1, is constitutively
      transported to the cytosol, whereas a mutant containing alanine at this site
      remains in the nucleus. The export can be blocked by leptomycin B, indicating
      active and receptor-mediated nuclear export of FGF-1. Thapsigargin, but not
      leptomycin B, prevents the appearance of active PKCdelta in the nucleus, and FGF
      1 is in this case phosphorylated in the cytosol. Leptomycin B increases the
      amount of phosphorylated FGF-1 in the cells by preventing dephosphorylation of
      the growth factor, which seems to occur more rapidly in the cytoplasm than in the
      nucleus. The nucleocytoplasmic trafficking of the phosphorylated growth factor is
      likely to play a role in the activity of internalized FGF-1.

PMID- 15574886
TI  - Colorimetric method for identifying plant essential oil components that affect
      biofilm formation and structure.
AB  - The specific biofilm formation (SBF) assay, a technique based on crystal violet
      staining, was developed to locate plant essential oils and their components that
      affect biofilm formation. SBF analysis determined that cinnamon, cassia, and
      citronella oils differentially affected growth-normalized biofilm formation by
      Escherichia coli. Examination of the corresponding essential oil principal
      components by the SBF assay revealed that cinnamaldehyde decreased biofilm
      formation compared to biofilms grown in Luria-Bertani broth, eugenol did not
      result in a change, and citronellol increased the SBF. To evaluate these results,
      two microscopy-based assays were employed. First, confocal laser scanning
      microscopy (CLSM) was used to examine E. coli biofilms cultivated in flow cells,
      which were quantitatively analyzed by COMSTAT, an image analysis program. The
      overall trend for five parameters that characterize biofilm development
      corroborated the findings of the SBF assay. Second, the results of an assay
      measuring growth-normalized adhesion by direct microscopy concurred with the
      results of the SBF assay and CLSM imaging. Viability staining indicated that
      there was reduced toxicity of the essential oil components to cells in biofilms
      compared to the toxicity to planktonic cells but revealed morphological damage to
      E. coli after cinnamaldehyde exposure. Cinnamaldehyde also inhibited the swimming
      motility of E. coli. SBF analysis of three Pseudomonas species exposed to
      cinnamaldehyde, eugenol, or citronellol revealed diverse responses. The SBF assay
      could be useful as an initial step for finding plant essential oils and their
      components that affect biofilm formation and structure.

PMID- 15574885
TI  - ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell
      differentiation.
AB  - Knowledge on molecular systems involved in myogenic precursor cell (mpc) fusion
      into myotubes is fragmentary. Previous studies have implicated the a disintegrin
      and metalloproteinase (ADAM) family in most mammalian cell fusion processes.
      ADAM12 is likely involved in fusion of murine mpc and human rhabdomyosarcoma
      cells, but it requires yet unknown molecular partners to launch myogenic cell
      fusion. ADAM12 was shown able to mediate cell-to-cell attachment through binding
      alpha9beta1 integrin. We report that normal human mpc express both ADAM12 and
      alpha9beta1 integrin during their differentiation. Expression of alpha9 parallels
      that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12
      coimmunoprecipitate and participate to mpc adhesion. Inhibition of
      ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense
      oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc
      fusion by 47-48%, with combination of both strategies increasing inhibition up to
      62%. By contrast with blockade of vascular cell adhesion molecule-1/alpha4beta1,
      which also reduced fusion, exposure to ADAM12 antisense oligonucleotides or anti
      alpha9beta1 antibody did not induce detachment of mpc from extracellular matrix,
      suggesting specific involvement of ADAM12-alpha9beta1 interaction in the fusion
      process. Evaluation of the fusion rate with regard to the size of myotubes showed
      that both ADAM12 antisense oligonucleotides and alpha9beta1 blockade inhibited
      more importantly formation of large (> or =5 nuclei) myotubes than that of small
      (2-4 nuclei) myotubes. We conclude that both ADAM12 and alpha9beta1 integrin are
      expressed during postnatal human myogenic differentiation and that their
      interaction is mainly operative in nascent myotube growth.

PMID- 15574887
TI  - Characterization of the novel Fusobacterium nucleatum plasmid pKH9 and evidence
      of an addiction system.
AB  - Fusobacterium nucleatum is an important oral anaerobic pathogen involved in
      periodontal and systemic infections. Studies of the molecular mechanisms involved
      in fusobacterial virulence and adhesion have been limited by lack of systems for
      efficient genetic manipulation. Plasmids were isolated from eight strains of F.
      nucleatum. The smallest plasmid, pKH9 (4,975 bp), was characterized and used to
      create new vectors for fusobacterial genetic manipulation. DNA sequence analysis
      of pKH9 revealed an open reading frame (ORF) encoding a putative autonomous
      rolling circle replication protein (Rep), an ORF predicted to encode a protein
      homologous to members of the FtsK/SpoIIIE cell division-DNA segregation protein
      family, and an operon encoding a putative toxin-antitoxin plasmid addiction
      system (txf-axf). Deletion analysis localized the pKH9 replication region in a
      0.96-kbp fragment. The pKH9 rep gene is not present in this fragment, suggesting
      that pKH9 can replicate in fusobacteria independently of the Rep protein. A pKH9
      based, compact Escherichia coli-F. nucleatum shuttle plasmid was constructed and
      found to be compatible with a previously described pFN1-based fusobacterial
      shuttle plasmid. Deletion of the pKH9 putative addiction system (txf-axf) reduced
      plasmid stability in fusobacteria, indicating its addiction properties and
      suggesting it to be the first plasmid addiction system described for
      fusobacteria. pKH9, its genetic elements, and its shuttle plasmid derivatives can
      serve as useful tools for investigating fusobacterial properties important in
      biofilm ecology and pathogenesis.

PMID- 15574888
TI  - Inactivation of viruses in bubbling processes utilized for personal bioaerosol
      monitoring.
AB  - A new personal bioaerosol sampler has recently been developed and evaluated for
      sampling of viable airborne bacteria and fungi under controlled laboratory
      conditions and in the field. The operational principle of the device is based on
      the passage of air through porous medium immersed in liquid. This process leads
      to the formation of bubbles within the filter as the carrier gas passes through
      and thus provides effective mechanisms for aerosol removal. As demonstrated in
      previous studies, the culturability of sampled bacterium and fungi remained high
      for the entire 8-h sampling period. The present study is the first step of the
      evaluation of the new sampler for monitoring of viable airborne viruses. It
      focuses on the investigation of the inactivation rate of viruses in the bubbling
      process during 4 h of continuous operation. Four microbes were used in this
      study, influenza, measles, mumps, and vaccinia viruses. It was found that the use
      of distilled water as the collection fluid was associated with a relatively high
      decay rate. A significant improvement was achieved by utilizing virus maintenance
      fluid prepared by using Hank's solution with appropriate additives. The survival
      rates of the influenza, measles, and mumps viruses were increased by 1.4 log,
      0.83 log, and 0.82 log, respectively, after the first hour of operation compared
      to bubbling through the sterile water. The same trend was observed throughout the
      entire 4-h experiment. There was no significant difference observed only for the
      robust vaccinia virus.

PMID- 15574889
TI  - Use of Pseudomonas putida EstA as an anchoring motif for display of a periplasmic
      enzyme on the surface of Escherichia coli.
AB  - The functional expression of proteins on the surface of bacteria has proven
      important for numerous biotechnological applications. In this report, we
      investigated the N-terminal fusion display of the periplasmic enzyme beta
      lactamase (Bla) on the surface of Escherichia coli by using the translocator
      domain of the Pseudomonas putida outer membrane esterase (EstA), which is a
      member of the lipolytic autotransporter enzymes. To find out the transport
      function of a C-terminal domain of EstA, we generated a set of Bla-EstA fusion
      proteins containing N-terminally truncated derivatives of the EstA C-terminal
      domain. The surface exposure of the Bla moiety was verified by whole-cell
      immunoblots, protease accessibility, and fluorescence-activated cell sorting. The
      investigation of growth kinetics and host cell viability showed that the presence
      of the EstA translocator domain in the outer membrane neither inhibits cell
      growth nor affects cell viability. Furthermore, the surface-exposed Bla moiety
      was shown to be enzymatically active. These results demonstrate for the first
      time that the translocator domain of a lipolytic autotransporter enzyme is an
      effective anchoring motif for the functional display of heterologous passenger
      protein on the surface of E. coli. This investigation also provides a possible
      topological model of the EstA translocator domain, which might serve as a basis
      for the construction of fusion proteins containing heterologous passenger
      domains.

PMID- 15574890
TI  - Chitinase gene sequences retrieved from diverse aquatic habitats reveal
      environment-specific distributions.
AB  - Chitin is an abundant biopolymer whose degradation is mediated primarily by
      bacterial chitinases. We developed a degenerate PCR primer set to amplify a
      approximately 900-bp fragment of family 18, group I chitinase genes and used it
      to retrieve these gene fragments from environmental samples. Clone libraries of
      presumptive chitinase genes were created for nine water and six sediment samples
      from 10 aquatic environments including freshwater and saline lakes, estuarine
      water and sediments, and the central Arctic Ocean. Putative chitinase sequences
      were also retrieved from the Sargasso Sea metagenome sequence database. We were
      unable to obtain PCR product with these primers from an alkaline, hypersaline
      lake (Mono Lake, California). In total, 108 partial chitinase gene sequences were
      analyzed, with a minimum of 5 and a maximum of 13 chitinase sequences obtained
      from each library. All chitinase sequences were novel compared to previously
      identified sequences. Intralibrary sequence diversity was low, while we found
      significant differences between libraries from different water column samples and
      between water column and sediment samples. However, identical sequences were
      retrieved from samples collected at widely distributed locations that did not
      necessarily represent similar environments, suggesting homogeneity of
      chitinoclastic communities between some environments.

PMID- 15574891
TI  - Design and production in Aspergillus niger of a chimeric protein associating a
      fungal feruloyl esterase and a clostridial dockerin domain.
AB  - A chimeric enzyme associating feruloyl esterase A (FAEA) from Aspergillus niger
      and dockerin from Clostridium thermocellum was produced in A. niger. A completely
      truncated form was produced when the dockerin domain was located downstream of
      the FAEA (FAEA-Doc), whereas no chimeric protein was produced when the bacterial
      dockerin domain was located upstream of the FAEA (Doc-FAEA). Northern blot
      analysis showed similar transcript levels for the two constructs, indicating a
      posttranscriptional bottleneck for Doc-FAEA production. The sequence encoding the
      first 514 amino acids from A. niger glucoamylase and a dibasic proteolytic
      processing site (kex-2) were fused upstream of the Doc-FAEA sequence. By using
      this fusion strategy, the esterase activity found in the extracellular medium was
      20-fold-higher than that of the wild-type reference strain, and the production
      yield was estimated to be about 100 mg of chimeric protein/liter. Intracellular
      and extracellular production was analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, dockerin-cohesin interaction assays, and
      Western blotting. Labeled cohesins detected an intact extracellular Doc-FAEA of
      about 43 kDa and a cleaved-off dockerin domain of about 8 kDa. In addition, an
      intracellular 120-kDa protein was recognized by using labeled cohesins and
      antibodies raised against FAEA. This protein corresponded to the unprocessed Doc
      FAEA form fused to glucoamylase. In conclusion, these results indicated that
      translational fusion to glucoamylase improved the secretion efficiency of a
      chimeric Doc-FAEA protein and allowed production of the first functional fungal
      enzyme joined to a bacterial dockerin.

PMID- 15574892
TI  - Initiation of protein synthesis by a labeled derivative of the Lactobacillus
      casei DN-114 001 strain during transit from the stomach to the cecum in mice
      harboring human microbiota.
AB  - Although studies on the survival of bacteria in the digestive tract have been
      reported in the literature, little data are available on the physiological
      adaptation of probiotics to the digestive environment. In previous work, a
      transcriptional fusion system (i.e., luciferase genes under the control of a
      deregulated promoter) was used to demonstrate that a derivative of the
      Lactobacillus casei DN-114 001 strain, ingested in a fermented milk and thus
      exhibiting initially a very weak metabolic activity, synthesized proteins de novo
      after its transit in the digestive tract of mice harboring human microbiota
      (known as human-microbiota-associated mice). With the same genetic system and
      animal model, we here investigate for the first time the ability of L. casei to
      reinitiate synthesis in the different digestive tract compartments. In this
      study, most ingested L. casei cells transited from the stomach to the duodenum
      jejunum within 1 h postingestion. No luciferase activity was observed in these
      digestive tract compartments after the first hour. At later times, the bulk of
      bacteria had transited to the ileum and the cecum. Luciferase synthesis was
      detected between 1.5 and 2.0 h postingestion at the ileal level and from 1.5 h to
      at least 6.0 h postingestion in the cecum, where the activity remained at a
      maximum level. These results demonstrate that ingested L. casei (derivative of
      the DN-114 001 strain) administered via a fermented milk has already reinitiated
      protein synthesis when it reaches the ileal and cecal compartments.

PMID- 15574893
TI  - Microarray and functional gene analyses of sulfate-reducing prokaryotes in low
      sulfate, acidic fens reveal cooccurrence of recognized genera and novel lineages.
AB  - Low-sulfate, acidic (approximately pH 4) fens in the Lehstenbach catchment in the
      Fichtelgebirge mountains in Germany are unusual habitats for sulfate-reducing
      prokaryotes (SRPs) that have been postulated to facilitate the retention of
      sulfur and protons in these ecosystems. Despite the low in situ availability of
      sulfate (concentration in the soil solution, 20 to 200 microM) and the acidic
      conditions (soil and soil solution pHs, approximately 4 and 5, respectively), the
      upper peat layers of the soils from two fens (Schloppnerbrunnen I and II) of this
      catchment displayed significant sulfate-reducing capacities. 16S rRNA gene-based
      oligonucleotide microarray analyses revealed stable diversity patterns for
      recognized SRPs in the upper 30 cm of both fens. Members of the family
      "Syntrophobacteraceae" were detected in both fens, while signals specific for the
      genus Desulfomonile were observed only in soils from Schloppnerbrunnen I. These
      results were confirmed and extended by comparative analyses of environmentally
      retrieved 16S rRNA and dissimilatory (bi)sulfite reductase (dsrAB) gene
      sequences; dsrAB sequences from Desulfobacca-like SRPs, which were not identified
      by microarray analysis, were obtained from both fens. Hypotheses concerning the
      ecophysiological role of these three SRP groups in the fens were formulated based
      on the known physiological properties of their cultured relatives. In addition to
      these recognized SRP lineages, six novel dsrAB types that were phylogenetically
      unrelated to all known SRPs were detected in the fens. These dsrAB sequences had
      no features indicative of pseudogenes and likely represent novel, deeply
      branching, sulfate- or sulfite-reducing prokaryotes that are specialized
      colonists of low-sulfate habitats.

PMID- 15574894
TI  - Genetic and biochemical characterization of field-evolved resistance to Bacillus
      thuringiensis toxin Cry1Ac in the diamondback moth, Plutella xylostella.
AB  - The long-term usefulness of Bacillus thuringiensis Cry toxins, either in sprays
      or in transgenic crops, may be compromised by the evolution of resistance in
      target insects. Managing the evolution of resistance to B. thuringiensis toxins
      requires extensive knowledge about the mechanisms, genetics, and ecology of
      resistance genes. To date, laboratory-selected populations have provided
      information on the diverse genetics and mechanisms of resistance to B.
      thuringiensis, highly resistant field populations being rare. However, the
      selection pressures on field and laboratory populations are very different and
      may produce resistance genes with distinct characteristics. In order to better
      understand the genetics, biochemical mechanisms, and ecology of field-evolved
      resistance, a diamondback moth (Plutella xylostella) field population (Karak)
      which had been exposed to intensive spraying with B. thuringiensis subsp.
      kurstaki was collected from Malaysia. We detected a very high level of resistance
      to Cry1Ac; high levels of resistance to B. thuringiensis subsp. kurstaki Cry1Aa,
      Cry1Ab, and Cry1Fa; and a moderate level of resistance to Cry1Ca. The toxicity of
      Cry1Ja to the Karak population was not significantly different from that to a
      standard laboratory population (LAB-UK). Notable features of the Karak population
      were that field-selected resistance to B. thuringiensis subsp. kurstaki did not
      decline at all in unselected populations over 11 generations in laboratory
      microcosm experiments and that resistance to Cry1Ac declined only threefold over
      the same period. This finding may be due to a lack of fitness costs expressed by
      resistance strains, since such costs can be environmentally dependent and may not
      occur under ordinary laboratory culture conditions. Alternatively, resistance in
      the Karak population may have been near fixation, leading to a very slow increase
      in heterozygosity. Reciprocal genetic crosses between Karak and LAB-UK
      populations indicated that resistance was autosomal and recessive. At the highest
      dose of Cry1Ac tested, resistance was completely recessive, while at the lowest
      dose, it was incompletely dominant. A direct test of monogenic inheritance based
      on a backcross of F1 progeny with the Karak population suggested that resistance
      to Cry1Ac was controlled by a single locus. Binding studies with 125I-labeled
      Cry1Ab and Cry1Ac revealed greatly reduced binding to brush border membrane
      vesicles prepared from this field population.

PMID- 15574895
TI  - Comparison of two alternative dominant selectable markers for wine yeast
      transformation.
AB  - Genetic improvement of industrial yeast strains is restricted by the availability
      of selectable transformation markers. Antibiotic resistance markers have to be
      avoided for public health reasons, while auxotrophy markers are generally not
      useful for wine yeast strain transformation because most industrial Saccharomyces
      cerevisiae strains are prototrophic. For this work, we performed a comparative
      study of the usefulness of two alternative dominant selectable markers in both
      episomic and centromeric plasmids. Even though the selection for sulfite
      resistance conferred by FZF1-4 resulted in a larger number of transformants for a
      laboratory strain, the p-fluoro-DL-phenylalanine resistance conferred by ARO4-OFP
      resulted in a more suitable selection marker for all industrial strains tested.
      Both episomic and centromeric constructions carrying this marker resulted in
      transformation frequencies close to or above 10(3) transformants per microg of
      DNA for the three wine yeast strains tested.

PMID- 15574896
TI  - Protocol for specific isolation of virulent strains of Vibrio vulnificus serovar
      E (biotype 2) from environmental samples.
AB  - The eel pathogen Vibrio vulnificus biotype 2 comprises at least three serovars,
      with serovar E being the only one involved in both epizootics of eel vibriosis
      and sporadic cases of human infections. The virulent strains of this serovar
      (VSE) have only been recovered from clinical (mainly eel tissue) sources. The
      main objective of this work was to design and validate a new protocol for VSE
      specific isolation from environmental samples. The key element of the new
      protocol is the broth used for the first step (saline eel serum broth [SEB]),
      which contains eel serum as a nutritive and selective component. This approach
      takes advantage of the ability of VSE cells to grow in eel serum and thus to
      separate themselves from the pool of competitors. The growth yield in SEB after 8
      h of incubation was 1,000 times higher for VSE strains than for their putative
      competitors (including biotype 1 strains of the species). The selective and
      differential agar Vibrio vulnificus medium (VVM) was selected from five selective
      media for the second step because it gave the highest plating efficiency not only
      for the VSE group but also for other V. vulnificus groups, including biotype 3.
      The entire protocol was validated by field studies, with alkaline peptone water
      plus VVM as a control. V. vulnificus was isolated by both protocols, but serovar
      E was only recovered by the new method described here. All selected serovar E
      isolates were identified as VSE since they were virulent for both eels and iron
      overloaded mice and resisted the bactericidal action of eel and iron-overloaded
      human sera. In conclusion, this new protocol is a suitable method for the
      isolation of VSE strains from environmental samples and is recommended for
      epidemiological studies of the pathogenic serovar E.

PMID- 15574897
TI  - Broad-host-range plasmid pJB658 can be used for industrial-level production of a
      secreted host-toxic single-chain antibody fragment in Escherichia coli.
AB  - In industrial scale recombinant protein production it is often of interest to be
      able to translocate the product to reduce downstream costs, and heterologous
      proteins may require the oxidative environment outside of the cytoplasm for
      correct folding. High-level expression combined with translocation to the
      periplasm is often toxic to the host, and expression systems that can be used to
      fine-tune the production levels are therefore important. We previously
      constructed vector pJB658, which harbors the broad-host-range RK2 minireplicon
      and the inducible Pm/xylS promoter system, and we here explore the potential of
      this unique system to manipulate the expression and translocation of a host-toxic
      single-chain antibody variable fragment with affinity for hapten 2-phenyloxazol-5
      one (phOx) (scFv-phOx). Fine-tuning of scFv-phOx levels was achieved by varying
      the concentrations of inducers and the vector copy number and also different
      signal sequences. Our data show that periplasmic accumulation of scFv-phOx leads
      to cell lysis, and we demonstrate the importance of controlled and high
      expression rates to achieve high product yields. By optimizing such parameters we
      show that soluble scFv-phOx could be produced to a high volumetric yield (1.2
      g/liter) in high-cell-density cultures of Escherichia coli.

PMID- 15574898
TI  - Evaluation of the Biological Sampling Kit (BiSKit) for large-area surface
      sampling.
AB  - Current surface sampling methods for microbial contaminants are designed to
      sample small areas and utilize culture analysis. The total number of microbes
      recovered is low because a small area is sampled, making detection of a potential
      pathogen more difficult. Furthermore, sampling of small areas requires a greater
      number of samples to be collected, which delays the reporting of results, taxes
      laboratory resources and staffing, and increases analysis costs. A new biological
      surface sampling method, the Biological Sampling Kit (BiSKit), designed to sample
      large areas and to be compatible with testing with a variety of technologies,
      including PCR and immunoassay, was evaluated and compared to other surface
      sampling strategies. In experimental room trials, wood laminate and metal
      surfaces were contaminated by aerosolization of Bacillus atrophaeus spores, a
      simulant for Bacillus anthracis, into the room, followed by settling of the
      spores onto the test surfaces. The surfaces were sampled with the BiSKit, a
      cotton-based swab, and a foam-based swab. Samples were analyzed by culturing,
      quantitative PCR, and immunological assays. The results showed that the large
      surface area (1 m2) sampled with the BiSKit resulted in concentrations of B.
      atrophaeus in samples that were up to 10-fold higher than the concentrations
      obtained with the other methods tested. A comparison of wet and dry sampling with
      the BiSKit indicated that dry sampling was more efficient (efficiency, 18.4%)
      than wet sampling (efficiency, 11.3%). The sensitivities of detection of B.
      atrophaeus on metal surfaces were 42 +/- 5.8 CFU/m2 for wet sampling and 100.5 +/
      10.2 CFU/m2 for dry sampling. These results demonstrate that the use of a
      sampling device capable of sampling larger areas results in higher sensitivity
      than that obtained with currently available methods and has the advantage of
      sampling larger areas, thus requiring collection of fewer samples per site.

PMID- 15574899
TI  - Diagnostic real-time PCR for detection of Salmonella in food.
AB  - A robust 5' nuclease (TaqMan) real-time PCR was developed and validated in-house
      for the specific detection of Salmonella in food. The assay used specifically
      designed primers and a probe target within the ttrRSBCA locus, which is located
      near the Salmonella pathogenicity island 2 at centisome 30.5. It is required for
      tetrathionate respiration in Salmonella. The assay correctly identified all 110
      Salmonella strains and 87 non-Salmonella strains tested. An internal
      amplification control, which is coamplified with the same primers as the
      Salmonella DNA, was also included in the assay. The detection probabilities were
      70% when a Salmonella cell suspension containing 10(3) CFU/ml was used as a
      template in the PCR (5 CFU per reaction) and 100% when a suspension of 10(4)
      CFU/ml was used. A pre-PCR sample preparation protocol including a preenrichment
      step in buffered peptone water followed by DNA extraction-purification was
      applied when 110 various food samples (chicken rinses, minced meat, fish, and raw
      milk) were investigated for Salmonella. The diagnostic accuracy was shown to be
      100% compared to the traditional culture method. The overall analysis time of the
      PCR method was approximately 24 h, in contrast to 4 to 5 days of analysis time
      for the traditional culture method. This methodology can contribute to meeting
      the increasing demand of quality assurance laboratories for standard diagnostic
      methods. Studies are planned to assess the interlaboratory performance of this
      diagnostic PCR method.

PMID- 15574900
TI  - Sulfate-reducing bacteria in tubes constructed by the marine infaunal polychaete
      Diopatra cuprea.
AB  - Marine infaunal burrows and tubes greatly enhance solute transport between
      sediments and the overlying water column and are sites of elevated microbial
      activity. Biotic and abiotic controls of the compositions and activities of
      burrow and tube microbial communities are poorly understood. The microbial
      communities in tubes of the marine infaunal polychaete Diopatria cuprea collected
      from two different sediment habitats were examined. The bacterial communities in
      the tubes from a sandy sediment differed from those in the tubes from a muddy
      sediment. The difference in community structure also extended to the sulfate
      reducing bacterial (SRB) assemblage, although it was not as pronounced for this
      functional group of species. PCR-amplified 16S rRNA gene sequences recovered from
      Diopatra tube SRB by clonal library construction and screening were all related
      to the family Desulfobacteriaceae. This finding was supported by phospholipid
      fatty acid analysis and by hybridization of 16S rRNA probes specific for members
      of the genera Desulfosarcina, Desulfobacter, Desulfobacterium, Desulfobotulus,
      Desulfococcus, and Desulfovibrio and some members of the genera Desulfomonas,
      Desulfuromonas, and Desulfomicrobium with 16S rRNA gene sequences resolved by
      denaturing gradient gel electrophoresis. Two of six SRB clones from the clone
      library were not detected in tubes from the sandy sediment. The habitat in which
      the D. cuprea tubes were constructed had a strong influence on the tube bacterial
      community as a whole, as well as on the SRB assemblage.

PMID- 15574901
TI  - Influence of applied volume on efficacy of 3-minute surgical reference
      disinfection method prEN 12791.
AB  - For assessment of the efficacy of surgical hand disinfection, European reference
      method prEN 12791 prescribes that the hands must be kept wet with the reference
      alcohol for 3 min regardless of the applied volume. The aim of this study was to
      determine whether the applied volume of the reference disinfectant n-propanol
      (60%, vol/vol) influences the effect on the resident hand flora. Ten experiments
      with 200 reference disinfections were analyzed. Hands were washed for 1 min with
      soap. The bacterial prevalue was obtained by rubbing fingertips in tryptic soy
      broth for 1 min. After this, each subject treated the hands with n-propanol (60%,
      vol/vol) by using as many portions as necessary to keep hands wet for a total of
      3 min. Bacterial postvalues (immediate effect) were obtained for one hand, and
      the other hand was gloved for 3 h. After the gloves were taken off, a second
      postvalue was obtained (sustained effect). Most surgical reference disinfections
      (73%) were achieved with 9 ml of the reference alcohol, followed by 12 ml (24%)
      and 6 ml (3%). There was no significant difference between the mean log10
      reduction values for the three treatment groups, both in terms of the immediate
      effect (P = 0.333, as determined by analysis of variance) and in terms of the
      sustained effect (P = 0.442). A higher number of portions did not correlate with
      a higher reduction factor (for immediate effect, Pearson's correlation
      coefficient = -0.028 [P = 0.689]; for sustained effect, Pearson's correlation
      coefficient = 0.059 [P = 0.404]). If the hands were kept wet with the reference
      alcohol for the total application time, the applied volume could vary, but this
      did not alter the efficacy.

PMID- 15574902
TI  - Bacterial life and dinitrogen fixation at a gypsum rock.
AB  - The organisms of a bluish-green layer beneath the shards of a gypsum rock were
      characterized by molecular techniques. The cyanobacterial consortium consisted
      almost exclusively of Chroococcidiopsis spp. The organisms of the shards
      expressed nitrogenase activity (C2H2 reduction) aerobically and in light. After a
      prolonged period of drought at the rock, the cells were inactive, but they
      resumed nitrogenase activity 2 to 3 days after the addition of water. In a
      suspension culture of Chroococcidiopsis sp. strain PCC7203, C2H2 reduction
      required microaerobic conditions and was strictly dependent on low light
      intensities. Sequencing of a segment of the nitrogenase reductase gene (nifH)
      indicated that Chroococcidiopsis possesses the alternative molybdenum nitrogenase
      2, expressed in Anabaena variabilis only under reduced O2 tensions, rather than
      the widespread, common molybdenum nitrogenase. The shards apparently provide
      microsites with reduced light intensities and reduced O2 tension that allow N2
      fixation to proceed in the unicellular Chroococcidiopsis at the gypsum rock,
      unless the activity is due to minute amounts of other, very active cyanobacteria.
      Phylogenetic analysis of nifH sequences tends to suggest that molybdenum
      nitrogenase 2 is characteristic of those unicellular or filamentous,
      nonheterocystous cyanobacteria fixing N2 under microaerobic conditions only.

PMID- 15574903
TI  - Characterization of Lactobacillus coryniformis DSM 20001T surface protein Cpf
      mediating coaggregation with and aggregation among pathogens.
AB  - Phenotypic characterization of aggregation phenotypes of Lactobacillus
      coryniformis revealed that strain DSM 20001T coaggregated with Escherichia coli
      K88, Campylobacter coli, and Campylobacter jejuni but not with other human
      pathogens. In addition, cells of these pathogens aggregated in the presence of
      the spent culture supernatant (SCS) of strain DSM 20001T. Cells of E. coli K88
      remained viable in the coaggregates and aggregates for up to 24 h. Both
      coaggregation and aggregation (co/aggregation) occurred at pH 3.5 to 7.5 and was
      sensitive to heat (85 degrees C for 15 min) and proteinase K. The co/aggregation
      promoting factor (Cpf) was purified, and the gene was identified by PCR with
      degenerate primers derived from internal amino acid sequences. The cpf gene
      encoded a 19.9-kDa preprotein with a sec-dependent leader and an isoelectric
      point of 4.4. The amino acid sequence had no significant similarity to proteins
      with known functions. Northern analysis revealed not only major transcription
      from the promoter of cpf but also major transcription from the promoter of the
      preceding insertion element, ISLco1 belonging to the IS3 family. Recombinant Cpf
      produced in E. coli mediated aggregation of pathogens comparable to the
      aggregation obtained with purified Cpf or SCS of strain DSM 20001T. Cpf could be
      removed from cells of strain DSM 20001T by treatment with 5 M LiCl and could be
      subsequently reattached to the cell surface by using SCS or recombinant Cpf,
      which resulted in restoration of the co/aggregation property. These results
      together with those of the amino acid sequence analysis suggest that Cpf is a
      novel surface protein of L. coryniformis that mediates co/aggregation of some
      pathogens.

PMID- 15574904
TI  - Identification of a novel dioxygenase involved in metabolism of o-xylene,
      toluene, and ethylbenzene by Rhodococcus sp. strain DK17.
AB  - Rhodococcus sp. strain DK17 is able to grow on o-xylene, benzene, toluene, and
      ethylbenzene. DK17 harbors at least two megaplasmids, and the genes encoding the
      initial steps in alkylbenzene metabolism are present on the 330-kb pDK2. The
      genes encoding alkylbenzene degradation were cloned in a cosmid clone and
      sequenced completely to reveal 35 open reading frames (ORFs). Among the ORFs, we
      identified two nearly exact copies (one base difference) of genes encoding large
      and small subunits of an iron sulfur protein terminal oxygenase that are 6 kb
      apart from each other. Immediately downstream of one copy of the dioxygenase
      genes (akbA1a and akbA2a) is a gene encoding a dioxygenase ferredoxin component
      (akbA3), and downstream of the other copy (akbA1b and akbA2b) are genes
      putatively encoding a meta-cleavage pathway. RT-PCR experiments show that the two
      copies of the dioxygenase genes are operonic with the downstream putative
      catabolic genes and that both operons are induced by o-xylene. When expressed in
      Escherichia coli, AkbA1a-AkbA2a-AkbA3 transformed o-xylene into 2,3- and 3,4
      dimethylphenol. These were apparently derived from an unstable o-xylene cis-3,4
      dihydrodiol, which readily dehydrates. This indicates a single point of attack of
      the dioxygenase on the aromatic ring. In contrast, attack of AkbA1a-AkbA2a-AkbA3
      on ethylbenzene resulted in the formation of two different cis-dihydrodiols
      resulting from an oxidation at the 2,3 and the 3,4 positions on the aromatic
      ring, respectively.

PMID- 15574905
TI  - Biosynthetic gene cluster of the herbicide phosphinothricin tripeptide from
      Streptomyces viridochromogenes Tu494.
AB  - The antibiotic phosphinothricin tripeptide (PTT) consists of two molecules of L
      alanine and one molecule of the unusual amino acid phosphinothricin (PT) which
      are nonribosomally combined. The bioactive compound PT has bactericidal,
      fungicidal, and herbicidal properties and possesses a C-P-C bond, which is very
      rare in natural compounds. Previously uncharacterized flanking and middle regions
      of the PTT biosynthetic gene cluster from Streptomyces viridochromogenes Tu494
      were isolated and sequenced. The boundaries of the gene cluster were identified
      by gene inactivation studies. Sequence analysis and homology searches led to the
      completion of the gene cluster, which consists of 24 genes. Four of these were
      identified as undescribed genes coding for proteins that are probably involved in
      uncharacterized early steps of antibiotic biosynthesis or in providing precursors
      of PTT biosynthesis (phosphoenolpyruvate, acetyl-coenzyme A, or L-alanine). The
      involvement of the genes orfM and trs and of the regulatory gene prpA in PTT
      biosynthesis was analyzed by gene inactivation and overexpression, respectively.
      Insight into the regulation of PTT was gained by determining the transcriptional
      start sites of the pmi and prpA genes. A previously undescribed regulatory gene
      involved in morphological differentiation in streptomycetes was identified
      outside of the left boundary of the PTT biosynthetic gene cluster.

PMID- 15574906
TI  - Survival of cold-stressed Campylobacter jejuni on ground chicken and chicken skin
      during frozen storage.
AB  - Campylobacter jejuni is prevalent in poultry, but the effect of combined
      refrigerated and frozen storage on its survival, conditions relevant to poultry
      processing and storage, has not been evaluated. Therefore, the effects of
      refrigeration at 4 degrees C, freezing at -20 degrees C, and a combination of
      refrigeration and freezing on the survival of C. jejuni in ground chicken and on
      chicken skin were examined. Samples were enumerated using tryptic soy agar
      containing sheep's blood and modified cefoperazone charcoal deoxycholate agar.
      Refrigerated storage alone for 3 to 7 days produced a reduction in cell counts of
      0.34 to 0.81 log10 CFU/g in ground chicken and a reduction in cell counts of 0.31
      to 0.63 log10 CFU/g on chicken skin. Declines were comparable for each sample
      type using either plating medium. Frozen storage, alone and with
      prerefrigeration, produced a reduction in cell counts of 0.56 to 1.57 log10 CFU/g
      in ground chicken and a reduction in cell counts of 1.38 to 3.39 log10 CFU/g on
      chicken skin over a 2-week period. The recovery of C. jejuni following freezing
      was similar on both plating media. The survival following frozen storage was
      greater in ground chicken than on chicken skin with or without prerefrigeration.
      Cell counts after freezing were lower on chicken skin samples that had been
      prerefrigerated for 7 days than in those that had been prerefrigerated for 0, 1,
      or 3 days. This was not observed for ground chicken samples, possibly due to
      their composition. C. jejuni survived storage at 4 and -20 degrees C with either
      sample type. This study indicates that, individually or in combination,
      refrigeration and freezing are not a substitute for safe handling and proper
      cooking of poultry.

PMID- 15574907
TI  - Streptomyces coelicolor A3(2) lacks a genomic island present in the chromosome of
      Streptomyces lividans 66.
AB  - Streptomyces lividans ZX1 has become a preferred host for DNA cloning in
      Streptomyces species over its progenitor, the wild-type strain 66 (stock number
      1326 from the John Innes Center collection), especially when stable DNA is
      crucial for in vitro electrophoresis, because DNA from strain 66 contains a novel
      modification that makes it sensitive to oxidative double-strand cleavage during
      electrophoresis. Detailed analysis of this modification-deficient mutant (ZX1)
      revealed that it has several additional phenotypic traits associated with a
      chromosomal deletion of ca. 90 kb, which was cloned and mapped by using a cosmid
      library. Comparative sequence analysis of two clones containing the left and
      right deletion ends originating from strain 66 and one clone with the deletion
      and fused sequence cloned from strain ZX1 revealed a perfect 15-bp direct repeat,
      which may have mediated deletion and fusion to yield strain ZX1 by site-specific
      recombination. Analysis of AseI linking clones in the deleted region in relation
      to the published AseI map of strain ZX1 yielded a complete AseI map for the S.
      lividans 66 genome, on which the relative positions of a cloned phage phiHAU3
      resistance (phiHAU3r) gene and the dnd gene cluster were precisely localized.
      Comparison of S. lividans ZX1 and its progenitor 66, as well as the sequenced
      genome of its close relative, Streptomyces coelicolor M145, reveals that the ca.
      90-kb deletion in strain ZX1 may have originated from an insertion from an
      unknown source.

PMID- 15574908
TI  - Synthesis of novel lipids in Saccharomyces cerevisiae by heterologous expression
      of an unspecific bacterial acyltransferase.
AB  - The bifunctional wax ester synthase/acyl-coenzyme A:diacylglycerol
      acyltransferase (WS/DGAT) is the key enzyme in storage lipid accumulation in the
      gram-negative bacterium Acinetobacter calcoaceticus ADP1, mediating wax ester,
      and to a lesser extent, triacylglycerol (TAG) biosynthesis. Saccharomyces
      cerevisiae accumulates TAGs and steryl esters as storage lipids. Four genes
      encoding a DGAT (Dga1p), a phospholipid:diacylglycerol acyltransferase (Lro1p)
      and two acyl-coenzyme A:sterol acyltransferases (ASATs) (Are1p and Are2p) are
      involved in the final esterification steps in TAG and steryl ester biosynthesis
      in this yeast. In the quadruple mutant strain S. cerevisiae H1246, the disruption
      of DGA1, LRO1, ARE1, and ARE2 leads to an inability to synthesize storage lipids.
      Heterologous expression of WS/DGAT from A. calcoaceticus ADP1 in S. cerevisiae
      H1246 restored TAG but not steryl ester biosynthesis, although high levels of
      ASAT activity could be demonstrated for WS/DGAT expressed in Escherichia coli XL1
      Blue in radiometric in vitro assays with cholesterol and ergosterol as
      substrates. In addition to TAG synthesis, heterologous expression of WS/DGAT in
      S. cerevisiae H1246 resulted also in the accumulation of fatty acid ethyl esters
      as well as fatty acid isoamyl esters. In vitro studies confirmed that WS/DGAT is
      capable of utilizing a broad range of alcohols as substrates comprising long
      chain fatty alcohols like hexadecanol as well as short-chain alcohols like
      ethanol or isoamyl alcohol. This study demonstrated the highly unspecific
      acyltransferase activity of WS/DGAT from A. calcoaceticus ADP1, indicating the
      broad biocatalytic potential of this enzyme for biotechnological production of a
      large variety of lipids in vivo in prokaryotic as well as eukaryotic expression
      hosts.

PMID- 15574909
TI  - Mechanistic approach to the problem of hybridization efficiency in fluorescent in
      situ hybridization.
AB  - In fluorescent in situ hybridization (FISH), the efficiency of hybridization
      between the DNA probe and the rRNA has been related to the accessibility of the
      rRNA when ribosome content and cell permeability are not limiting. Published rRNA
      accessibility maps show that probe brightness is sensitive to the organism being
      hybridized and the exact location of the target site and, hence, it is highly
      unpredictable based on accessibility only. In this study, a model of FISH based
      on the thermodynamics of nucleic acid hybridization was developed. The model
      provides a mechanistic approach to calculate the affinity of the probe to the
      target site, which is defined as the overall Gibbs free energy change (DeltaG
      degrees overall) for a reaction scheme involving the DNA-rRNA and intramolecular
      DNA and rRNA interactions that take place during FISH. Probe data sets for the
      published accessibility maps and experiments targeting localized regions in the
      16S rRNA of Escherichia coli were used to demonstrate that DeltaG degrees overall
      is a strong predictor of hybridization efficiency and superior to conventional
      estimates based on the dissociation temperature of the DNA/rRNA duplex. The use
      of the proposed model also allowed the development of mechanistic approaches to
      increase probe brightness, even in seemingly inaccessible regions of the 16S
      rRNA. Finally, a threshold DeltaG degrees overall of -13.0 kcal/mol was proposed
      as a goal in the design of FISH probes to maximize hybridization efficiency
      without compromising specificity.

PMID- 15574910
TI  - A group II intron-type open reading frame from the thermophile Bacillus
      (Geobacillus) stearothermophilus encodes a heat-stable reverse transcriptase.
AB  - The production of a stable cDNA copy of an unstable RNA molecule by reverse
      transcription is a widely used and essential technology for many important
      applications, such as the construction of gene libraries, production of DNA
      probes, and analysis of gene expression by reverse transcriptase PCR (RT-PCR).
      However, the synthesis of full-length cDNAs is frequently inefficient, because
      the RT commonly used often produces truncated cDNAs. Synthesizing cDNA at higher
      temperatures, on the other hand, can provide a number of improvements. These
      include increasing the length of cDNA product, greater accuracy, and greater
      specificity during reverse transcription. Thus, an RT that remains stable and
      active at hot temperatures may produce better-quality cDNAs and improve the yield
      of full-length cDNAs. Described here is the discovery of a gene, designated trt,
      from the genome of the thermophilic bacterium Bacillus (Geobacillus)
      stearothermophilus strain 10. The gene codes for an open reading frame (ORF)
      similar to the ORFs encoded by group II introns found in bacteria. The gene was
      cloned and overexpressed in Escherichia coli, and its protein product was
      partially purified. Like the host organism, the Trt protein is a heat-stable
      protein with RT activity and can reverse transcribe RNA at temperatures as high
      as 75 degrees C.

PMID- 15574911
TI  - Cometabolism of a nongrowth substrate: L-serine utilization by Corynebacterium
      glutamicum.
AB  - Despite its key position in central metabolism, L-serine does not support the
      growth of Corynebacterium glutamicum. Nevertheless, during growth on glucose, L
      serine is consumed at rates up to 19.4 +/- 4.0 nmol min(-1) (mg [dry weight])(
      1), resulting in the complete consumption of 100 mM L-serine in the presence of
      100 mM glucose and an increased growth yield of about 20%. Use of 13C-labeled L
      serine and analysis of cellularly derived metabolites by nuclear magnetic
      resonance spectroscopy revealed that the carbon skeleton of L-serine is mainly
      converted to pyruvate-derived metabolites such as L-alanine. The sdaA gene was
      identified in the genome of C. glutamicum, and overexpression of sdaA resulted in
      (i) functional L-serine dehydratase (L-SerDH) activity, and therefore conversion
      of L-serine to pyruvate, and (ii) growth of the recombinant strain on L-serine as
      the single substrate. In contrast, deletion of sdaA decreased the L-serine
      cometabolism rate with glucose by 47% but still resulted in degradation of L
      serine to pyruvate. Cystathionine beta-lyase was additionally found to convert L
      serine to pyruvate, and the respective metC gene was induced 2.4-fold under high
      internal L-serine concentrations. Upon sdaA overexpression, the growth rate on
      glucose is reduced 36% from that of the wild type, illustrating that even with
      glucose as a single substrate, intracellular L-serine conversion to pyruvate
      might occur, although probably the weak affinity of L-SerDH (apparent Km, 11 mM)
      prevents substantial L-serine degradation.

PMID- 15574912
TI  - Restoration of gene function by homologous recombination: from PCR to gene
      expression in one step.
AB  - We have developed a simple method for single-step cloning of any PCR product into
      a plasmid. A novel selection principle has been applied, in which activation of a
      drug selection marker is achieved following homologous recombination. In this
      method a DNA fragment is amplified by PCR with standard oligonucleotides that
      contain flanking tails derived from the host plasmid and the complete lambdaPR or
      rrnA1 promoter regions. The resulting PCR product is then electroporated into an
      Escherichia coli strain harboring both the phage lambda Red functions and the
      host plasmid. Upon homologous recombination of the PCR fragment into the plasmid,
      expression of a drug selection marker is fully induced due to restoration of its
      truncated promoter, thus allowing appropriate selection. Recombinant plasmid
      vectors encoding beta-galactosidase and neomycin phosphotransferase were
      constructed by using this method in two well-known Red systems. This cloning
      strategy significantly reduces both the time and costs associated with cloning
      procedures.

PMID- 15574913
TI  - Development of a universal microarray based on the ligation detection reaction
      and 16S rrna gene polymorphism to target diversity of cyanobacteria.
AB  - The cyanobacteria are photosynthetic prokaryotes of significant ecological and
      biotechnological interest, since they strongly contribute to primary production
      and are a rich source of bioactive compounds. In eutrophic fresh and brackish
      waters, their mass occurrences (water blooms) are often toxic and constitute a
      high potential risk for human health. Therefore, rapid and reliable
      identification of cyanobacterial species in complex environmental samples is
      important. Here we describe the development and validation of a microarray for
      the identification of cyanobacteria in aquatic environments. Our approach is
      based on the use of a ligation detection reaction coupled to a universal array.
      Probes were designed for detecting 19 cyanobacterial groups including
      Anabaena/Aphanizomenon, Calothrix, Cylindrospermopsis, Cylindrospermum,
      Gloeothece, halotolerants, Leptolyngbya, Palau Lyngbya, Microcystis, Nodularia,
      Nostoc, Planktothrix, Antarctic Phormidium, Prochlorococcus, Spirulina,
      Synechococcus, Synechocystis, Trichodesmium, and Woronichinia. These groups were
      identified based on an alignment of over 300 cyanobacterial 16S rRNA sequences.
      For validation of the microarrays, 95 samples (24 axenic strains from culture
      collections, 27 isolated strains, and 44 cloned fragments recovered from
      environmental samples) were tested. The results demonstrated a high
      discriminative power and sensitivity to 1 fmol of the PCR-amplified 16S rRNA
      gene. Accurate identification of target strains was also achieved with unbalanced
      mixes of PCR amplicons from different cyanobacteria and an environmental sample.
      Our universal array method shows great potential for rapid and reliable
      identification of cyanobacteria. It can be easily adapted to future development
      and could thus be applied both in research and environmental monitoring.

PMID- 15574914
TI  - Prevalence and characterization of shiga toxin-producing Escherichia coli in
      swine feces recovered in the National Animal Health Monitoring System's Swine
      2000 study.
AB  - A study was conducted to determine the prevalence of Shiga toxin-producing
      Escherichia coli (STEC) in swine feces in the United States as part of the
      National Animal Health Monitoring System's Swine 2000 study. Fecal samples
      collected from swine operations from 13 of the top 17 swine-producing states were
      tested for the presence of STEC. After enrichment of swine fecal samples in
      tryptic soy broth, the samples were tested for the presence of stx1 and stx2 by
      use of the TaqMan E. coli STX1 and STX2 PCR assays. Enrichments of samples
      positive for stx1 and/or stx2 were plated, and colony hybridization was performed
      using digoxigenin-labeled probes complementary to the stx1 and stx2 genes.
      Positive colonies were picked and confirmed by PCR for the presence of the stx1,
      stx2, or stx2e genes, and the isolates were serotyped. Out of 687 fecal samples
      tested using the TaqMan assays, 70% (484 of 687) were positive for Shiga toxin
      genes, and 54% (370 of 687), 64% (436 of 687), and 38% (261 of 687) were positive
      for stx1, stx2, and both toxin genes, respectively. Out of 219 isolates that were
      characterized, 29 (13%) produced stx1, 14 (6%) produced stx2, and 176 (80%)
      produced stx2e. Twenty-three fecal samples contained at least two STEC strains
      that had different serotypes but that had the same toxin genes or included a
      strain that possessed stx1 in addition to a strain that possessed stx2 or stx2e.
      The STEC isolates belonged to various serogroups, including O2, O5, O7, O8, O9,
      OX10, O11, O15, OX18, O20, O57, O65, O68, O69, O78, O91, O96, O100, O101, O120,
      O121, O152, O159, O160, O163, and O untypeable. It is noteworthy that no isolates
      of serogroup O157 were recovered. Results of this study indicate that swine in
      the United States harbor STEC that can potentially cause human illness.

PMID- 15574915
TI  - Genogroup I and II noroviruses detected in stool samples by real-time reverse
      transcription-PCR using highly degenerate universal primers.
AB  - Genogroup I noroviruses from five genetic clusters and genogroup II noroviruses
      from eight genetic clusters were detected in stool extracts using degenerate
      primers and single-tube, real-time reverse transcription-PCR (RT-PCR) with SYBR
      Green detection. Two degenerate primer sets, designated MON 431-433 and MON 432
      434, were designed from consensus sequences from the major clusters of norovirus
      based on the RNA-dependent RNA polymerase region of the norovirus genome. Viruses
      were extracted from stool samples within 20 min using a viral RNA extraction kit.
      Real-time RT-PCR for noroviruses generated semiquantitative results by means of
      the cycle threshold data and dilution endpoint standard curves. Presumptive
      product verification was achieved by evaluation of first-derivative melt graphs.
      Multiple clusters of noroviruses were identified simultaneously in a multiplex
      fashion by virtue of slight differences in melting temperature. The detection of
      13 different genetic clusters suggests that the MON primers may serve as
      universal primers for most, if not all, of the noroviruses in a multiplex assay.
      Our technique provides a framework for broad application of real-time RT-PCR in
      clinical, environmental, and food testing laboratories for a wide range of
      noroviruses.

PMID- 15574916
TI  - Prevalence and seasonal variations of six bee viruses in Apis mellifera L. and
      Varroa destructor mite populations in France.
AB  - A survey of six bee viruses on a large geographic scale was undertaken by using
      seemingly healthy bee colonies and the PCR technique. Samples of adult bees and
      pupae were collected from 36 apiaries in the spring, summer, and autumn during
      2002. Varroa destructor samples were collected at the end of summer following
      acaricide treatment. In adult bees, during the year deformed wing virus (DWV) was
      found at least once in 97% of the apiaries, sacbrood virus (SBV) was found in 86%
      of the apiaries, chronic bee paralysis virus (CBPV) was found in 28% of the
      apiaries, acute bee paralysis virus (ABPV) was found in 58% of the apiaries,
      black queen cell virus (BQCV) was found in 86% of the apiaries, and Kashmir bee
      virus (KBV) was found in 17% of the apiaries. For pupae, the following
      frequencies were obtained: DWV, 94% of the apiaries; SBV, 80% of the apiaries;
      CBPV, none of the apiaries; ABPV, 23% of the apiaries; BQCV, 23% of the apiaries;
      and KBV, 6% of the apiaries. In Varroa samples, the following four viruses were
      identified: DWV (100% of the apiaries), SBV (45% of the apiaries), ABPV (36% of
      the apiaries), and KBV (5% of the apiaries). The latter findings support the
      putative role of mites in transmitting these viruses. Taken together, these data
      indicate that bee virus infections occur persistently in bee populations despite
      the lack of clinical signs, suggesting that colony disease outbreaks might result
      from environmental factors that lead to activation of viral replication in bees.

PMID- 15574917
TI  - Differentiation of the gene clusters encoding botulinum neurotoxin type A
      complexes in Clostridium botulinum type A, Ab, and A(B) strains.
AB  - We describe a strategy to identify the clusters of genes encoding components of
      the botulinum toxin type A (boNT/A) complexes in 57 strains of Clostridium
      botulinum types A, Ab, and A(B) isolated in Italy and in the United States from
      different sources. Specifically, we combined the results of PCR for detecting the
      ha33 and/or p47 genes with those of boNT/A PCR-restriction fragment length
      polymorphism analysis. Three different type A toxin gene clusters were revealed;
      type A1 was predominant among the strains from the United States, whereas type A2
      predominated among the Italian strains, suggesting a geographic distinction
      between strains. By contrast, no relationship between the toxin gene clusters and
      the clinical or food source of strains was evident. In two C. botulinum type A
      isolates from the United States, we recognized a third type A toxin gene cluster
      (designated type A3) which was similar to that previously described only for C.
      botulinum type A(B) and Ab strains. Total genomic DNA from the strains was
      subjected to pulsed-filed gel electrophoresis and randomly amplified polymorphic
      DNA analyses, and the results were consistent with the boNT/A gene clusters
      obtained.

PMID- 15574918
TI  - Bile-mediated aminoglycoside sensitivity in Lactobacillus species likely results
      from increased membrane permeability attributable to cholic acid.
AB  - Few studies have been conducted on antimicrobial resistance in lactobacilli,
      presumably because of their nonpathogenic nature as anaerobic commensals. We
      assessed resistance in 43 type strains and isolates representing 14 species by
      using agar disk diffusion and MIC analysis in MRS medium. Most noteworthy were
      two general phenotypes displayed by nearly every strain tested: (i) they were
      more susceptible (up to 256-fold in some cases) to the deconjugated bile acid
      cholic acid than to the conjugate taurocholic or taurodeoxycholic acid, and (ii)
      they became susceptible to aminoglycosides when assayed on agar medium containing
      0.5% fractionated bovine bile (ox gall). Two-dimensional MIC analyses of one
      representative strain, Lactobacillus plantarum WCFS1, at increasing
      concentrations of ox gall (0 to 30.3 mg/ml) displayed corresponding decreases in
      resistance to all of the aminoglycosides tested and ethidium bromide. This effect
      was clinically relevant, with the gentamicin MIC decreasing from >1,000 to 4
      mug/ml in just 3.8 mg of ox gall per ml. In uptake studies at pH 6.5, [G
      3H]gentamicin accumulation increased over control levels when cells of this
      strain were exposed to bile acids or reserpine but not when they were exposed to
      carbonyl cyanide m-chlorophenylhydrazone. The effect was dramatic, particularly
      with cholic acid, increasing up to 18-fold, whereas only modest increases, 3- and
      5-fold, could be achieved with taurocholic acid and ox gall, respectively. Since
      L. plantarum, particularly strain WCFS1, is known to encode bile salt hydrolase
      (deconjugation) activity, our data indicate that mainly cholic acid, but not
      taurocholic acid, effectively permeabilizes the membrane to aminoglycosides.
      However, at pHs approaching neutral conditions in the intestinal lumen,
      aminoglycoside resistance due to membrane impermeability may be complemented by a
      potential efflux mechanism.

PMID- 15574919
TI  - Allelic diversity and population structure in Oenococcus oeni as determined from
      sequence analysis of housekeeping genes.
AB  - Oenococcus oeni is the organism of choice for promoting malolactic fermentation
      in wine. The population biology of O. oeni is poorly understood and remains
      unclear. For a better understanding of the mode of genetic variation within this
      species, we investigated by using multilocus sequence typing (MLST) with the
      gyrB, pgm, ddl, recP, and mleA genes the genetic diversity and genetic
      relationships among 18 O. oeni strains isolated in various years from wines of
      the United States, France, Germany, Spain, and Italy. These strains have also
      been characterized by ribotyping and restriction fragment length polymorphism
      (RFLP) analysis of the PCR-amplified 16S-23S rRNA gene intergenic spacer region
      (ISR). Ribotyping grouped the strains into two groups; however, the RFLP analysis
      of the ISRs showed no differences in the strains analyzed. In contrast, MLST in
      oenococci had a good discriminatory ability, and we have found a higher genetic
      diversity than indicated by ribotyping analysis. All sequence types were
      represented by a single strain, and all the strains could be distinguished from
      each other because they had unique combinations of alleles. Strains assumed to be
      identical showed the same sequence type. Phylogenetic analyses indicated a
      panmictic population structure in O. oeni. Sequences were analyzed for evidence
      of recombination by split decomposition analysis and analysis of clustered
      polymorphisms. All results indicated that recombination plays a major role in
      creating the genetic heterogeneity of O. oeni. A low standardized index of
      association value indicated that the O. oeni genes analyzed are close to linkage
      equilibrium. This study constitutes the first step in the development of an MLST
      method for O. oeni and the first example of the application of MLST to a
      nonpathogenic food production bacteria.

PMID- 15574920
TI  - Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis
      of predominant bacteria in human feces.
AB  - 16S rRNA gene-targeted group-specific primers were designed and validated for
      specific detection and quantification of the Clostridium leptum subgroup and the
      Atopobium cluster. To monitor the predominant bacteria in human feces by real
      time PCR, we used these specific primers together with four sets of group
      specific primers for the Clostridium coccoides group, the Bacteroides fragilis
      group, Bifidobacterium, and Prevotella developed in a previous study (T. Matsuki,
      K. Watanabe, J. Fujimoto, Y. Miyamoto, T. Takada, K. Matsumoto, H. Oyaizu, and R.
      Tanaka, Appl. Environ. Microbiol. 68:5445-5451, 2002). Examination of DNA
      extracted from the feces of 46 healthy adults showed that the C. coccoides group
      was present in the greatest numbers (log10 10.3 +/- 0.3 cells per g [wet weight]
      [average +/- standard deviation]), followed by the C. leptum subgroup (log10 9.9
      +/- 0.7 cells per g [wet weight]), the B. fragilis group (log10 9.9 +/- 0.3 cells
      per g [wet weight]), Bifidobacterium (log10 9.4 +/- 0.7 cells per g [wet
      weight]), and the Atopobium cluster (log10 9.3 +/- 0.7 cells per g [wet weight]).
      These five bacterial groups were detected in all 46 volunteers. Prevotella was
      found in only 46% of the subjects at a level of log10 9.7 +/- 0.8 cells per g
      (wet weight). Examination of changes in the population and the composition of the
      intestinal flora for six healthy adults over an 8-month period revealed that the
      composition of the flora of each volunteer remained stable throughout the test
      period.

PMID- 15574921
TI  - Characterization of a novel amylolytic enzyme encoded by a gene from a soil
      derived metagenomic library.
AB  - It has been estimated that less than 1% of the microorganisms in nature can be
      cultivated by conventional techniques. Thus, the classical approach of isolating
      enzymes from pure cultures allows the analysis of only a subset of the total
      naturally occurring microbiota in environmental samples enriched in
      microorganisms. To isolate useful microbial enzymes from uncultured soil
      microorganisms, a metagenome was isolated from soil samples, and a metagenomic
      library was constructed by using the pUC19 vector. The library was screened for
      amylase activity, and one clone from among approximately 30,000 recombinant
      Escherichia coli clones showed amylase activity. Sequencing of the clone revealed
      a novel amylolytic enzyme expressed from a novel gene. The putative amylase gene
      (amyM) was overexpressed and purified for characterization. Optimal conditions
      for the enzyme activity of the AmyM protein were 42 degrees C and pH 9.0; Ca2+
      stabilized the activity. The amylase hydrolyzed soluble starch and cyclodextrins
      to produce high levels of maltose and hydrolyzed pullulan to panose. The enzyme
      showed a high transglycosylation activity, making alpha-(1, 4) linkages
      exclusively. The hydrolysis and transglycosylation properties of AmyM suggest
      that it has novel characteristics and can be regarded as an intermediate type of
      maltogenic amylase, alpha-amylase, and 4-alpha-glucanotransferase.

PMID- 15574922
TI  - Novel physiological features of Carboxydothermus hydrogenoformans and
      Thermoterrabacterium ferrireducens.
AB  - Carboxydothermus hydrogenoformans is able to grow by conversion of CO to H2 and
      CO2. Besides CO, only pyruvate was described as serving as an energy source.
      Based on 16S rRNA gene sequence similarity, C. hydrogenoformans is closely
      related to Thermoterrabacterium ferrireducens. T. ferrireducens is like C.
      hydrogenoformans a gram-positive, thermophilic, strict anaerobic bacterium.
      However, it is capable of using various electron donors and acceptors for growth.
      Growth of C. hydrogenoformans with multiple electron donors and acceptors was
      tested. C. hydrogenoformans oxidized formate, lactate, glycerol, CO, and H2 with
      9,10-anthraquinone-2,6-disulfonate as an electron acceptor. Sulfite, thiosulfate,
      sulfur, nitrate, and fumarate were reduced with lactate as an electron donor. T.
      ferrireducens oxidized CO with 9,10-anthraquinone-2,6-disulfonate as an electron
      acceptor but did not produce H2 from CO. In contrast to what was published
      before, T. ferrireducens was able to grow on lactate with sulfite, sulfur, and
      nitrate as electron acceptors.

PMID- 15574923
TI  - New integrative method to generate Bacillus subtilis recombinant strains free of
      selection markers.
AB  - The novel method described in this paper combines the use of blaI, which encodes
      a repressor involved in Bacillus licheniformis BlaP beta-lactamase regulation, an
      antibiotic resistance gene, and a B. subtilis strain (BS1541) that is
      conditionally auxotrophic for lysine. We constructed a BlaI cassette containing
      blaI and the spectinomycin resistance genes and two short direct repeat DNA
      sequences, one at each extremity of the cassette. The BS1541 strain was obtained
      by replacing the B. subtilis P(lysA) promoter with that of the P(blaP) beta
      lactamase promoter. In the resulting strain, the cloning of the blaI repressor
      gene confers lysine auxotrophy to BS1541. After integration of the BlaI cassette
      into the chromosome of a conditionally lys-auxotrophic (BS1541) strain by
      homologous recombination and positive selection for spectinomycin resistance, the
      eviction of the BlaI cassette was achieved by single crossover between the two
      short direct repeat sequences. This strategy was successfully used to inactivate
      a single gene and to introduce a gene of interest in the Bacillus chromosome. In
      both cases the resulting strains are free of selection marker. This allows the
      use of the BlaI cassette to repeatedly further modify the Bacillus chromosome.

PMID- 15574924
TI  - In situ expression of nifD in Geobacteraceae in subsurface sediments.
AB  - In order to determine whether the metabolic state of Geobacteraceae involved in
      bioremediation of subsurface sediments might be inferred from levels of mRNA for
      key genes, in situ expression of nifD, a highly conserved gene involved in
      nitrogen fixation, was investigated. When Geobacter sulfurreducens was grown
      without a source of fixed nitrogen in chemostats with acetate provided as the
      limiting electron donor and Fe(III) as the electron acceptor, levels of nifD
      transcripts were 4 to 5 orders of magnitude higher than in chemostat cultures
      provided with ammonium. In contrast, the number of transcripts of recA and the
      16S rRNA gene were slightly lower in the absence of ammonium. The addition of
      acetate to organic- and nitrogen-poor subsurface sediments stimulated the growth
      of Geobacteraceae and Fe(III) reduction, as well as the expression of nifD in
      Geobacteraceae. Levels of nifD transcripts in Geobacteraceae decreased more than
      100-fold within 2 days after the addition of 100 microM ammonium, while levels of
      recA and total bacterial 16S rRNA in Geobacteraceae remained relatively constant.
      Ammonium amendments had no effect on rates of Fe(III) reduction in acetate
      amended sediments or toluene degradation in petroleum-contaminated sediments,
      suggesting that other factors, such as the rate that Geobacteraceae could access
      Fe(III) oxides, limited Fe(III) reduction. These results demonstrate that it is
      possible to monitor one aspect of the in situ metabolic state of Geobacteraceae
      species in subsurface sediments via analysis of mRNA levels, which is the first
      step toward a more global analysis of in situ gene expression related to nutrient
      status and stress response during bioremediation by Geobacteraceae.

PMID- 15574925
TI  - Evidence for involvement of at least six proteins in adaptation of Lactobacillus
      sakei to cold temperatures and addition of NaCl.
AB  - Lactobacillus sakei is a lactic acid bacterium widely represented in the natural
      flora of fresh meat. The aim of this study was to analyze the differences in
      protein expression during environmental changes encountered during technological
      processes in which L. sakei is involved in order to gain insight into the ability
      of this species to grow and survive in such environments. Using two-dimensional
      electrophoresis, we observed significant variation of a set of 21 proteins in
      cells grown at 4 degrees C or in the presence of 4% NaCl. Six proteins could be
      identified by determination of their N-terminal sequences, and the corresponding
      gene clusters were studied. Two proteins belong to carbon metabolic pathways, and
      four can be clustered as general stress proteins. A phenotype was observed at low
      temperature for five of the six mutants constructed for these genes. The survival
      of four mutants during stationary phase at 4 degrees C was affected, and
      surprisingly, one mutant showed enhanced survival during stationary phase at low
      temperatures.

PMID- 15574926
TI  - Occurrence of microbial indicators and Clostridium perfringens in wastewater,
      water column samples, sediments, drinking water, and Weddell seal feces collected
      at McMurdo Station, Antarctica.
AB  - McMurdo Station, Antarctica, has discharged untreated sewage into McMurdo Sound
      for decades. Previous studies delineated the impacted area, which included the
      drinking water intake, by using total coliform and Clostridium perfringens
      concentrations. The estimation of risk to humans in contact with the impacted and
      potable waters may be greater than presumed, as these microbial indicators may
      not be the most appropriate for this environment. To address these concerns,
      concentrations of these and additional indicators (fecal coliforms, Escherichia
      coli, enterococci, coliphage, and enteroviruses) in the untreated wastewater,
      water column, and sediments of the impacted area and drinking water treatment
      facility and distribution system at McMurdo Station were determined. Fecal
      samples from Weddell seals in this area were also collected and analyzed for
      indicators. All drinking water samples were negative for indicators except for a
      single total coliform-positive sample. Total coliforms were present in water
      column samples at higher concentrations than other indicators. Fecal coliform and
      enterococcus concentrations were similar to each other and greater than those of
      other indicators in sediment samples closer to the discharge site. C. perfringens
      concentrations were higher in sediments at greater distances from the discharge
      site. Seal fecal samples contained concentrations of fecal coliforms, E. coli,
      enterococci, and C. perfringens similar to those found in untreated sewage. All
      samples were negative for enteroviruses. A wastewater treatment facility at
      McMurdo Station has started operation, and these data provide a baseline data set
      for monitoring the recovery of the impacted area. The contribution of seal feces
      to indicator concentrations in this area should be considered.

PMID- 15574927
TI  - Metabolic fluxes in Corynebacterium glutamicum during lysine production with
      sucrose as carbon source.
AB  - Metabolic fluxes in the central metabolism were determined for lysine-producing
      Corynebacterium glutamicum ATCC 21526 with sucrose as a carbon source, providing
      an insight into molasses-based industrial production processes with this
      organism. For this purpose, 13C metabolic flux analysis with parallel studies on
      [1-(13C)Fru]sucrose, [1-(13C)Glc]sucrose, and [13C6Fru]sucrose was carried out.
      C. glutamicum directed 27.4% of sucrose toward extracellular lysine. The strain
      exhibited a relatively high flux of 55.7% (normalized to an uptake flux of hexose
      units of 100%) through the pentose phosphate pathway (PPP). The glucose monomer
      of sucrose was completely channeled into the PPP. After transient efflux, the
      fructose residue was mainly taken up by the fructose-specific phosphotransferase
      system (PTS) and entered glycolysis at the level of fructose-1,6-bisphosphate.
      Glucose-6-phosphate isomerase operated in the gluconeogenetic direction from
      fructose-6-phosphate to glucose-6-phosphate and supplied additional carbon (7.2%)
      from the fructose part of the substrate toward the PPP. This involved supply of
      fructose-6-phosphate from the fructose part of sucrose either by PTS(Man) or by
      fructose-1,6-bisphosphatase. C. glutamicum further exhibited a high tricarboxylic
      acid (TCA) cycle flux of 78.2%. Isocitrate dehydrogenase therefore significantly
      contributed to the total NADPH supply of 190%. The demands for lysine (110%) and
      anabolism (32%) were lower than the supply, resulting in an apparent NADPH
      excess. The high TCA cycle flux and the significant secretion of dihydroxyacetone
      and glycerol display interesting targets to be approached by genetic engineers
      for optimization of the strain investigated.

PMID- 15574928
TI  - Seasonal incidence of autochthonous antagonistic Roseobacter spp. and
      Vibrionaceae strains in a turbot larva (Scophthalmus maximus) rearing system.
AB  - Bacteria inhibitory to fish larval pathogenic bacteria were isolated from two
      turbot larva rearing farms over a 1-year period. Samples were taken from the
      rearing site, e.g., tank walls, water, and feed for larvae, and bacteria with
      antagonistic activity against Vibrio anguillarum were isolated using a replica
      plating assay. Approximately 19,000 colonies were replica plated from marine agar
      plates, and 341 strains were isolated from colonies causing clearing zones in a
      layer of V. anguillarum. When tested in a well diffusion agar assay, 173 strains
      retained the antibacterial activity against V. anguillarum and Vibrio splendidus.
      Biochemical tests identified 132 strains as Roseobacter spp. and 31 as
      Vibrionaceae strains. Partial sequencing of the 16S rRNA gene of three strains
      confirmed the identification as Roseobacter gallaeciensis. Roseobacter spp. were
      especially isolated in the spring and early summer months. Subtyping of the 132
      Roseobacter spp. strains by randomly amplified polymorphic DNA with two primers
      revealed that the strains formed a very homogeneous group. Hence, it appears that
      the same subtype was present at both fish farms and persisted during the 1-year
      survey. This indicates either a common, regular source of the subtype or the
      possibility that a particular subtype has established itself in some areas of the
      fish farm. Thirty-one antagonists were identified as Vibrio spp., and 18 of these
      were V. anguillarum but not serotype O1 or O2. Roseobacter spp. strains were, in
      particular, isolated from the larval tank walls, and it may be possible to
      establish an antagonistic, beneficial microflora in the rearing environment of
      turbot larvae and thereby limit survival of pathogenic bacteria.

PMID- 15574929
TI  - Detection and quantification of Wallemia sebi in aerosols by real-time PCR,
      conventional PCR, and cultivation.
AB  - Wallemia sebi is a deuteromycete fungus commonly found in agricultural
      environments in many parts of the world and is suspected to be a causative agent
      of farmer's lung disease. The fungus grows slowly on commonly used culture media
      and is often obscured by the fast-growing fungi. Thus, its occurrence in
      different environments has often been underestimated. In this study, we developed
      two sets of PCR primers specific to W. sebi that can be applied in either
      conventional PCR or real-time PCR for rapid detection and quantification of the
      fungus in environmental samples. Both PCR systems proved to be highly specific
      and sensitive for W. sebi detection even in a high background of other fungal
      DNAs. These methods were employed to investigate the presence of W. sebi in the
      aerosols of a farm. The results revealed a high concentration of W. sebi spores,
      10(7) m(-3) by real-time PCR and 10(6) m(-3) by cultivation, which indicates the
      prevalence of W. sebi in farms handling hay and grain and in cow barns. The
      methods developed in this study could serve as rapid, specific, and sensitive
      means of detecting W. sebi in aerosol and surface samples and could thus
      facilitate investigations of its distribution, ecology, clinical diagnosis, and
      exposure risk assessment.

PMID- 15574930
TI  - Molecular and genetic characterization of propionicin F, a bacteriocin from
      Propionibacterium freudenreichii.
AB  - This work describes the purification and characterization of propionicin F, the
      first bacteriocin isolated from Propionibacterium freudenreichii. The bacteriocin
      has a bactericidal activity and is only active against strains of P.
      freudenreichii. Propionicin F appears to be formed through a processing pathway
      new to bacteriocins. The mass of the purified bacteriocin was determined by mass
      spectrometry, and the N-terminal amino acid sequence was determined by Edman
      degradation. Sequencing of pcfA, the bacteriocin structural gene, revealed that
      propionicin F corresponds to a 43-amino-acid peptide in the central part of a 255
      amino-acid open reading frame, suggesting that mature propionicin F is excised
      from the probacteriocin by N- and C-terminal proteolytic modifications. DNA
      sequencing and Northern blot hybridizations revealed that pcfA is cotranscribed
      with genes encoding a putative proline peptidase and a protein from the radical S
      adenosylmethionine family. A gene encoding an ABC transporter was also identified
      in close proximity to the bacteriocin structural gene. The potential role of
      these genes in propionicin F maturation and secretion is discussed.

PMID- 15574931
TI  - Comparison of proteolytic activities produced by entomopathogenic Photorhabdus
      bacteria: strain- and phase-dependent heterogeneity in composition and activity
      of four enzymes.
AB  - Twenty strains (including eight phase variant pairs) of nematode-symbiotic and
      insect-pathogenic Photorhabdus bacteria were examined for the production of
      proteolytic enzymes by using a combination of several methods, including gelatin
      liquefaction, zymography coupled to native and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and activity measurement with two chromogen
      substrate types. Four protease activities (approximately 74, approximately 55,
      approximately 54, and approximately 37 kDa) could be separated. The N-terminal
      sequences of three of the proteases were determined, and a comparison with
      sequences in databases allowed identification of these proteases as HEXXH
      metallopeptidases. Thus, the 74-kDa protease (described formerly as Php-B [J.
      Marokhazi, G. Koczan, F. Hudecz, L. Graf, A. Fodor, and I. Venekei, Biochem. J.
      379:633-640, 2004) is an ortholog of OpdA, a member the thimet oligopeptidase
      family, and the 55-kDa protease is an ortholog of PrtA, a HEXXH+H peptidase in
      clan MB (metzincins), while the 37-kDa protease (Php-C) belongs to the HEXXH+E
      peptidases in clan MA. The 54-kDa protease (Php-D) is a nonmetalloenzyme. PrtA
      and Php-C were zymographically detected, and they occurred in several smaller
      forms as well. OpdA could not be detected by zymography. PrtA, Php-C, and Php-D
      were secreted proteases; OpdA, in contrast, was an intracellular enzyme. OpdA
      activity was found in every strain tested, while Php-D was detected only in the
      Brecon/1 strain. There was significant strain variation in the secretion of PrtA
      and Php-C activities, but reduced activity or a lack of activity was not specific
      to secondary-phase variants. The presence of PrtA, OpdA, and Php-C activities
      could be detected in the hemolymph of Galleria melonella larvae 20 to 40 h
      postinfection. These proteases appear not to be directly involved in the
      pathogenicity of Photorhabdus, since strains or phase variants lacking any of
      these proteases do not show reduced virulence when they are injected into G.
      melonella larvae.

PMID- 15574932
TI  - Pressure inactivation of Bacillus endospores.
AB  - The inactivation of bacterial endospores by hydrostatic pressure requires the
      combined application of heat and pressure. We have determined the resistance of
      spores of 14 food isolates and 5 laboratory strains of Bacillus subtilis, B.
      amyloliquefaciens, and B. licheniformis to treatments with pressure and
      temperature (200 to 800 MPa and 60 to 80 degrees C) in mashed carrots. A large
      variation in the pressure resistance of spores was observed, and their reduction
      by treatments with 800 MPa and 70 degrees C for 4 min ranged from more than 6 log
      units to no reduction. The sporulation conditions further influenced their
      pressure resistance. The loss of dipicolinic acid (DPA) from spores that varied
      in their pressure resistance was determined, and spore sublethal injury was
      assessed by determination of the detection times for individual spores. Treatment
      of spores with pressure and temperature resulted in DPA-free, phase-bright
      spores. These spores were sensitive to moderate heat and exhibited strongly
      increased detection times as judged by the time required for single spores to
      grow to visible turbidity of the growth medium. The role of DPA in heat and
      pressure resistance was further substantiated by the use of the DPA-deficient
      mutant strain B. subtilis CIP 76.26. Taken together, these results indicate that
      inactivation of spores by combined pressure and temperature processing is
      achieved by a two-stage mechanism that does not involve germination. At a
      pressure between 600 and 800 MPa and a temperature greater than 60 degrees C, DPA
      is released predominantly by a physicochemical rather than a physiological
      process, and the DPA-free spores are inactivated by moderate heat independent of
      the pressure level. Relevant target organisms for pressure and temperature
      treatment of foods are proposed, namely, strains of B. amyloliquefaciens, which
      form highly pressure-resistant spores.

PMID- 15574933
TI  - Molecular characterization of a dechlorinating community resulting from in situ
      biostimulation in a trichloroethene-contaminated deep, fractured basalt aquifer
      and comparison to a derivative laboratory culture.
AB  - Sodium lactate additions to a trichloroethene (TCE) residual source area in deep,
      fractured basalt at a U.S. Department of Energy site have resulted in the
      enrichment of the indigenous microbial community, the complete dechlorination of
      nearly all aqueous-phase TCE to ethene, and the continued depletion of the
      residual source since 1999. The bacterial and archaeal consortia in groundwater
      obtained from the residual source were assessed by using PCR-amplified 16S rRNA
      genes. A clone library of bacterial amplicons was predominated by those from
      members of the class Clostridia (57 of 93 clones), of which a phylotype most
      similar to that of the homoacetogen Acetobacterium sp. strain HAAP-1 was most
      abundant (32 of 93 clones). The remaining Bacteria consisted of phylotypes
      affiliated with Sphingobacteria, Bacteroides, Spirochaetes, Mollicutes, and
      Proteobacteria and candidate divisions OP11 and OP3. The two proteobacterial
      phylotypes were most similar to those of the known dechlorinators Trichlorobacter
      thiogenes and Sulfurospirillum multivorans. Although not represented by the
      bacterial clones generated with broad-specificity bacterial primers, a
      Dehalococcoides-like phylotype was identified with genus-specific primers. Only
      four distinct phylotypes were detected in the groundwater archaeal library,
      including predominantly a clone affiliated with the strictly acetoclastic
      methanogen Methanosaeta concilii (24 of 43 clones). A mixed culture that
      completely dechlorinates TCE to ethene was enriched from this groundwater, and
      both communities were characterized by terminal restriction fragment length
      polymorphism (T-RFLP). According to T-RFLP, the laboratory enrichment community
      was less diverse overall than the groundwater community, with 22 unique
      phylotypes as opposed to 43 and a higher percentage of Clostridia, including the
      Acetobacterium population. Bioreactor archaeal structure was very similar to that
      of the groundwater community, suggesting that methane is generated primarily via
      the acetoclastic pathway, using acetate generated by lactate fermentation and
      acetogenesis in both systems.

PMID- 15574934
TI  - In vivo 31P nuclear magnetic resonance investigation of tellurite toxicity in
      Escherichia coli.
AB  - Here we compare the physiological state of Escherichia coli exposed to tellurite
      or selenite by using the noninvasive technique of phosphorus-31 nuclear magnetic
      resonance (NMR) spectroscopy. We studied glucose-fed Escherichia coli HB101 cells
      containing either a normal pUC8 plasmid with no tellurite resistance determinants
      present or the pTWT100 plasmid which contains the resistance determinants tehAB.
      No differences could be observed in intracellular ATP levels, the presence or
      absence of a transmembrane pH gradient, or the levels of phosphorylated
      glycolytic intermediates when resistant cells were studied by 31P NMR in the
      presence or absence of tellurite. In the sensitive strain, we observed that the
      transmembrane pH gradient was dissipated and intracellular ATP levels were
      rapidly depleted upon exposure to tellurite. Only the level of phosphorylated
      glycolytic intermediates remained the same as observed with resistant cells. Upon
      exposure to selenite, no differences could be observed by 31P NMR between
      resistant and sensitive strains, suggesting that the routes for selenite and
      tellurite reduction within the cells differ significantly, since only tellurite
      is able to collapse the transmembrane pH gradient and lower ATP levels in
      sensitive cells. The presence of the resistance determinant tehAB, by an as yet
      unidentified detoxification event, protects the cells from uncoupling by
      tellurite.

PMID- 15574935
TI  - Identification and functional analysis of the gene encoding methionine-gamma
      lyase in Brevibacterium linens.
AB  - The enzymatic degradation of L-methionine and subsequent formation of volatile
      sulfur compounds (VSCs) is believed to be essential for flavor development in
      cheese. L-methionine-gamma-lyase (MGL) can convert L-methionine to methanethiol
      (MTL), alpha-ketobutyrate, and ammonia. The mgl gene encoding MGL was cloned from
      the type strain Brevibacterium linens ATCC 9175 known to produce copious amounts
      of MTL and related VSCs. The disruption of the mgl gene, achieved in strain ATCC
      9175, resulted in a 62% decrease in thiol-producing activity and a 97% decrease
      in total VSC production in the knockout strain. Our work shows that L-methionine
      degradation via gamma-elimination is a key step in the formation of VSCs in B.
      linens.

PMID- 15574936
TI  - PCR analysis of the distribution of unicellular cyanobacterial diazotrophs in the
      Arabian Sea.
AB  - An oligonucleotide primer, NITRO821R, targeting the 16S rRNA gene of unicellular
      cyanobacterial N2 fixers was developed based on newly derived sequences from
      Crocosphaera sp. strain WH 8501 and Cyanothece sp. strains WH 8902 and WH 8904 as
      well as several previously described sequences of Cyanothece sp. and sequences of
      intracellular cyanobacterial symbionts of the marine diatom Climacodium
      frauenfeldianum. This oligonucleotide is specific for the targeted organisms,
      which represent a well-defined phylogenetic lineage, and can detect as few as 50
      cells in a standard PCR when it is used as a reverse primer together with the
      cyanobacterium- and plastid-specific forward primer CYA359F (U. Nubel, F. Garcia
      Pichel, and G. Muyzer, Appl. Environ. Microbiol. 63:3327-3332, 1997). Use of this
      primer pair in the PCR allowed analysis of the distribution of marine unicellular
      cyanobacterial diazotrophs along a transect following the 67 degrees E meridian
      from Victoria, Seychelles, to Muscat, Oman (0.5 degrees S to 26 degrees N) in the
      Arabian Sea. These organisms were found to be preferentially located in warm (>29
      degrees C) oligotrophic subsurface waters between 0 and 7 degrees N, but they
      were also found at a station north of Oman at 26 degrees N, 56 degrees 35'E,
      where similar water column conditions prevailed. Slightly cooler oligotrophic
      waters (<29 degrees C) did not contain these organisms or the numbers were
      considerably reduced, suggesting that temperature is a key factor in dictating
      the abundance of this unicellular cyanobacterial diazotroph lineage in marine
      environments.

PMID- 15574937
TI  - Milk contamination and resistance to processing conditions determine the fate of
      Lactococcus lactis bacteriophages in dairies.
AB  - Milk contamination by phages, the susceptibility of the phages to pasteurization,
      and the high levels of resistance to phage infection of starter strains condition
      the evolution dynamics of phage populations in dairy environments. Approximately
      10% (83 of 900) of raw milk samples contained phages of the quasi-species c2
      (72%), 936 (24%), and P335 (4%). However, 936 phages were isolated from 20 of 24
      (85%) whey samples, while c2 was detected in only one (4%) of these samples. This
      switch may have been due to the higher susceptibility of c2 to pasteurization
      (936-like phages were found to be approximately 35 times more resistant than c2
      strains to treatment of contaminated milk in a plate heat exchanger at 72 degrees
      C for 15 s). The restriction patterns of 936-like phages isolated from milk and
      whey were different, indicating that survival to pasteurization does not result
      in direct contamination of the dairy environment. The main alternative source of
      phages (commercial bacterial starters) does not appear to significantly
      contribute to phage contamination. Twenty-four strains isolated from nine starter
      formulations were generally resistant to phage infection, and very small progeny
      were generated upon induction of the lytic cycle of resident prophages. Thus, we
      postulate that a continuous supply of contaminated milk, followed by
      pasteurization, creates a factory environment rich in diverse 936 phage strains.
      This equilibrium would be broken if a particular starter strain turned out to be
      susceptible to infection by one of these 936-like phages, which, as a
      consequence, became prevalent.

PMID- 15574938
TI  - Quantification of tetracycline resistance genes in feedlot lagoons by real-time
      PCR.
AB  - A new real-time PCR method is presented that detects and quantifies three
      tetracycline resistance (Tcr) genes [tet(O), tet(W), and tet(Q)] in mixed
      microbial communities resident in feedlot lagoon wastewater. Tcr gene real-time
      TaqMan primer-probe sets were developed and optimized to quantify the Tcr genes
      present in seven different cattle feedlot lagoons, to validate the method, and to
      assess whether resistance gene concentrations correlate with free-tetracycline
      levels in lagoon waters. The method proved to be sensitive across a wide range of
      gene concentrations and provided consistent and reproducible results from complex
      lagoon water samples. The log10 of the sum of the three resistance gene
      concentrations was correlated with free-tetracycline levels (r2 = 0.50, P <
      0.001; n = 18), with the geometric means of individual resistance concentrations
      ranging from 4- to 8.3-fold greater in lagoon samples with above-median
      tetracycline levels (>1.95 microg/liter by enzyme-linked immunosorbent assay
      techniques) than in below-median lagoon samples. Of the three Tcr genes tested,
      tet(W) and tet(Q) were more commonly found in lagoon water samples. Successful
      development of this real-time PCR assay will permit other studies quantifying Tcr
      gene numbers in environmental and other samples.

PMID- 15574939
TI  - Bacterial diversity in a nonsaline alkaline environment: heterotrophic aerobic
      populations.
AB  - Heterotrophic populations were isolated and characterized from an alkaline
      groundwater environment generated by active serpentinization, which results in a
      Ca(OH)2-enriched, extremely diluted groundwater with pH 11.4. One hundred eighty
      five strains were isolated in different media at different pH values during two
      sampling periods. To assess the degree of diversity present in the environment
      and to select representative strains for further characterization of the
      populations, we screened the isolates by using random amplified polymorphic DNA
      PCR profiles and grouped them based on similarities determined by fatty acid
      methyl ester analysis. Phenotypic characterization, determinations of G+C
      content, phylogenetic analyses by direct sequencing of 16S rRNA genes, and
      determinations of pH tolerance were performed with the selected isolates.
      Although 38 different populations were identified and characterized, the vast
      majority of the isolates were gram positive with high G+C contents and were
      affiliated with three distinct groups, namely, strains closely related to the
      species Dietzia natrolimnae (32% of the isolates), to
      Frigoribacterium/Clavibacter lineages (29% of the isolates), and to the type
      strain of Microbacterium kitamiense (20% of the isolates). Other isolates were
      phylogenetically related to strains of the genera Agrococcus, Leifsonia,
      Kytococcus, Janibacter, Kocuria, Rothia, Nesterenkonia, Citrococcus, Micrococcus,
      Actinomyces, Rhodococcus, Bacillus, and Staphylococcus. Only five isolates were
      gram negative: one was related to the Sphingobacteria lineage and the other four
      were related to the alpha-Proteobacteria lineage. Despite the pH of the
      environment, the vast majority of the populations were alkali tolerant, and only
      two strains were able to grow at pH 11.

PMID- 15574940
TI  - Novel type of heme-dependent oxygenase catalyzes oxidative cleavage of rubber
      (poly-cis-1,4-isoprene).
AB  - An extracellular protein with strong absorption at 406 nm was purified from cell
      free culture fluid of latex-grown Xanthomonas sp. strain 35Y. This protein was
      identical to the gene product of a recently characterized gene cloned from
      Xanthomonas sp., as revealed by determination of m/z values and sequencing of
      selected isolated peptides obtained after trypsin fingerprint analysis. The
      purified protein degraded both natural rubber latex and chemosynthetic poly(cis
      1,4-isoprene) in vitro by oxidative cleavage of the double bonds of poly(cis-1,4
      isoprene). 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (m/z 236) was identified and
      unequivocally characterized as the major cleavage product, and there was a
      homologous series of minor metabolites that differed from the major degradation
      product only in the number of repetitive isoprene units between terminal
      functions, CHO-CH2--and--H2-COCH3. An in vitro enzyme assay for oxidative rubber
      degradation was developed based on high-performance liquid chromatography
      analysis and spectroscopic detection of product carbonyl functions after
      derivatization with dinitrophenylhydrazone. Enzymatic cleavage of rubber by the
      purified protein was strictly dependent on the presence of oxygen; it did not
      require addition of any soluble cofactors or metal ions and was optimal around pH
      7.0 at 40 degrees C. Carbon monoxide and cyanide inhibited the reaction; addition
      of catalase had no effect, and peroxidase activity could not be detected. The
      purified protein was specific for natural rubber latex and chemosynthetic
      poly(cis-1,4-isoprene). Analysis of the amino acid sequence deduced from the
      cloned gene (roxA [rubber oxygenase]) revealed the presence of two heme-binding
      motifs (CXXCH) for covalent attachment of heme to the protein. Spectroscopic
      analysis confirmed the presence of heme, and approximately 2 mol of heme per mol
      of RoxA was found.

PMID- 15574941
TI  - Integral strategy for evaluation of fecal indicator performance in bird
      influenced saline inland waters.
AB  - Wild birds are an important nonpoint source of fecal contamination of surface
      waters, but their contribution to fecal pollution is mostly difficult to
      estimate. Thus, to evaluate the relation between feces production and input of
      fecal indicator bacteria (FIB) into aquatic environments by wild waterfowl, we
      introduced a new holistic approach for evaluating the performance of FIB in six
      shallow saline habitats. For this, we monitored bird abundance, fecal pellet
      production, and the abundance of FIB concomitantly with a set of environmental
      variables over a 9-month period. For estimating fecal pellet production, a new
      protocol of fecal pellet counting was introduced, which was called fecal taxation
      (FTX). We could show that, over the whole range of investigated habitats, bird
      abundance, FTX values, and FIB abundance were highly significantly correlated and
      could demonstrate the good applicability of the FTX as a meaningful surrogate
      parameter for recent bird abundances and fecal contamination by birds in shallow
      aquatic ecosystems. Presumptive enterococci (ENT) were an excellent surrogate
      parameter of recent fecal contamination in these saline environments for samples
      collected at biweekly to monthly sampling intervals while presumptive Escherichia
      coli and fecal coliforms (FC) were often undetectable. Significant negative
      correlations with salinity indicated that E. coli and FC survival was hampered by
      osmotic stress. Statistical analyses further revealed that fecal pollution
      associated parameters represented one system component independent from other
      environmental variables and that, besides feces production, rainfall, total
      suspended solids (direct), and trophy (indirect) had significant positive effects
      on ENT concentrations. Our holistic approach of linking bird abundance, feces
      production, and FIB detection with environmental variables may serve as a
      powerful model for application to other aquatic ecosystems.

PMID- 15574942
TI  - Uranyl precipitation by Pseudomonas aeruginosa via controlled polyphosphate
      metabolism.
AB  - The polyphosphate kinase gene from Pseudomonas aeruginosa was overexpressed in
      its native host, resulting in the accumulation of 100 times the polyphosphate
      seen with control strains. Degradation of this polyphosphate was induced by
      carbon starvation conditions, resulting in phosphate release into the medium. The
      mechanism of polyphosphate degradation is not clearly understood, but it appears
      to be associated with glycogen degradation. Upon suspension of the cells in 1 mM
      uranyl nitrate, nearly all polyphosphate that had accumulated was degraded within
      48 h, resulting in the removal of nearly 80% of the uranyl ion and >95% of lesser
      concentrated solutions. Electron microscopy, energy-dispersive X-ray
      spectroscopy, and time-resolved laser-induced fluorescence spectroscopy (TRLFS)
      suggest that this removal was due to the precipitation of uranyl phosphate at the
      cell membrane. TRLFS also indicated that uranyl was initially sorbed to the cell
      as uranyl hydroxide and was then precipitated as uranyl phosphate as phosphate
      was released from the cell. Lethal doses of radiation did not halt phosphate
      secretion from polyphosphate-filled cells under carbon starvation conditions.

PMID- 15574943
TI  - Cadmium-responsive thiols in the ectomycorrhizal fungus Paxillus involutus.
AB  - Molecular and cellular mechanisms underlying the sustained metal tolerance of
      ectomycorrhizal fungi are largely unknown. Some of the main mechanisms involved
      in metal detoxification appear to involve the chelation of metal ions in the
      cytosol with thiol-containing compounds, such as glutathione, phytochelatins, or
      metallothioneins. We used an improved high-performance liquid chromatography
      method for the simultaneous measurement of thiol-containing compounds from
      cysteine and its derivatives (gamma-glutamylcysteine, glutathione) to higher
      molecular-mass compounds (phytochelatins). We found that glutathione and gamma
      glutamylcysteine contents increased when the ectomycorrhizal fungus Paxillus
      involutus was exposed to cadmium. An additional compound with a 3-kDa molecular
      mass, most probably related to a metallothionein, increased drastically in
      mycelia exposed to cadmium. The relative lack of phytochelatins and the presence
      of a putative metallothionein suggest that ectomycorrhizal fungi may use a
      different means to tolerate heavy metals, such as Cd, than do their plant hosts.

PMID- 15574944
TI  - Hypothesis for the role of nutrient starvation in biofilm detachment.
AB  - A combination of experimental and theoretical approaches was used to investigate
      the role of nutrient starvation as a potential trigger for biofilm detachment.
      Experimental observations of detachment in a variety of biofilm systems were made
      with pure cultures of Pseudomonas aeruginosa. These observations indicated that
      biofilms grown under continuous-flow conditions detached after flow was stopped,
      that hollow cell clusters were sometimes observed in biofilms grown in flow
      cells, and that lysed cells were apparent in the internal strata of colony
      biofilms. When biofilms were nutrient starved under continuous-flow conditions,
      detachment still occurred, suggesting that starvation and not the accumulation of
      a metabolic product was responsible for triggering detachment in this particular
      system. A cellular automata computer model of biofilm dynamics was used to
      explore the starvation-dependent detachment mechanism. The model predicted
      biofilm structures and dynamics that were qualitatively similar to those observed
      experimentally. The predicted features included centrally located voids appearing
      in sufficiently large cell clusters, gradients in growth rate within these
      clusters, and the release of most of the biofilm with simulated stopped-flow
      conditions. The model was also able to predict biofilm sloughing resulting solely
      from this detachment mechanism. These results support the conjecture that
      nutrient starvation is an environmental cue for the release of microbes from a
      biofilm.

PMID- 15574946
TI  - Detection of pathogenic Vibrio spp. in shellfish by using multiplex PCR and DNA
      microarrays.
AB  - This study describes the development of a gene-specific DNA microarray coupled
      with multiplex PCR for the comprehensive detection of pathogenic vibrios that are
      natural inhabitants of warm coastal waters and shellfish. Multiplex PCR with vvh
      and viuB for Vibrio vulnificus, with ompU, toxR, tcpI, and hlyA for V. cholerae,
      and with tlh, tdh, trh, and open reading frame 8 for V. parahaemolyticus helped
      to ensure that total and pathogenic strains, including subtypes of the three
      Vibrio spp., could be detected and discriminated. For DNA microarrays,
      oligonucleotide probes for these targeted genes were deposited onto epoxysilane
      derivatized, 12-well, Teflon-masked slides by using a MicroGrid II arrayer.
      Amplified PCR products were hybridized to arrays at 50 degrees C and detected by
      using tyramide signal amplification with Alexa Fluor 546 fluorescent dye. Slides
      were imaged by using an arrayWoRx scanner. The detection sensitivity for pure
      cultures without enrichment was 10(2) to 10(3) CFU/ml, and the specificity was
      100%. However, 5 h of sample enrichment followed by DNA extraction with Instagene
      matrix and multiplex PCR with microarray hybridization resulted in the detection
      of 1 CFU in 1 g of oyster tissue homogenate. Thus, enrichment of the bacterial
      pathogens permitted higher sensitivity in compliance with the Interstate
      Shellfish Sanitation Conference guideline. Application of the DNA microarray
      methodology to natural oysters revealed the presence of V. vulnificus (100%) and
      V. parahaemolyticus (83%). However, V. cholerae was not detected in natural
      oysters. An assay involving a combination of multiplex PCR and DNA microarray
      hybridization would help to ensure rapid and accurate detection of pathogenic
      vibrios in shellfish, thereby improving the microbiological safety of shellfish
      for consumers.

PMID- 15574945
TI  - Shear rate moderates community diversity in freshwater biofilms.
AB  - The development of freshwater multispecies biofilms at solid-liquid interfaces
      occurs both in quiescent waters and under conditions of high shear rates.
      However, the influence of hydrodynamic shear rates on bacterial biofilm diversity
      is poorly understood. We hypothesized that different shear rates would
      significantly influence biofilm diversity and alter the relative proportions of
      coaggregating and autoaggregating community isolates. In order to study this
      hypothesis, freshwater biofilms were developed at five shear rates (<0.1 to 305
      S(-1)) in a rotating concentric cylinder reactor fed with untreated potable
      water. Eubacterial diversity was assessed by denaturing gradient gel
      electrophoresis (DGGE) and culturing on R2A agar. Fifty morphologically distinct
      biofilm strains and 16 planktonic strains were isolated by culturing and
      identified by partial 16S rRNA gene sequencing, and their relatedness was
      determined by the construction of a neighbor-joining phylogenetic tree.
      Phylogenetic and DGGE analyses showed an inverse relationship between shear rate
      and bacterial diversity. An in vitro aggregation assay was used to assess the
      relative proportions of coaggregating and autoaggregating species from each
      biofilm. The highest proportion of autoaggregating bacteria was present at high
      shear rates (198 to 305 S(-1)). The intermediate shear rate (122 S(-1)) selected
      for the highest proportion of coaggregating bacteria (47%, or 17 of a possible 36
      coaggregation interactions). Under static conditions (<0.1 S(-1)), 41 (33%) of a
      possible 125 coaggregation interactions were positive. Few coaggregation (3.3%)
      or autoaggregation (25%) interactions occurred between the 16 planktonic strains.
      In conclusion, these data show that shear rates affect biofilm diversity as well
      as the relative proportions of aggregating bacteria.

PMID- 15574947
TI  - Characterization of C1-metabolizing prokaryotic communities in methane seep
      habitats at the Kuroshima Knoll, southern Ryukyu Arc, by analyzing pmoA, mmoX,
      mxaF, mcrA, and 16S rRNA genes.
AB  - Samples from three submerged sites (MC, a core obtained in the methane seep area;
      MR, a reference core obtained at a distance from the methane seep; and HC, a gas
      bubbling carbonate sample) at the Kuroshima Knoll in the southern Ryuku arc were
      analyzed to gain insight into the organisms present and the processes involved in
      this oxic-anoxic methane seep environment. 16S rRNA gene analyses by quantitative
      real-time PCR and clone library sequencing revealed that the MC core sediments
      contained abundant archaea (approximately 34% of the total prokaryotes),
      including both mesophilic methanogens related to the genus Methanolobus and ANME
      2 members of the Methanosarcinales, as well as members of the delta
      Proteobacteria, suggesting that both anaerobic methane oxidation and
      methanogenesis occurred at this site. In addition, several functional genes
      connected with methane metabolism were analyzed by quantitative competitive-PCR,
      including the genes encoding particulate methane monooxygenase (pmoA), soluble
      methane monooxygenase (mmoX), methanol dehydrogenese (mxaF), and methyl coenzyme
      M reductase (mcrA). In the MC core sediments, the most abundant gene was mcrA
      (2.5 x 10(6) copies/g [wet weight]), while the pmoA gene of the type I
      methanotrophs (5.9 x 10(6) copies/g [wet weight]) was most abundant at the
      surface of the MC core. These results indicate that there is a very complex
      environment in which methane production, anaerobic methane oxidation, and aerobic
      methane oxidation all occur in close proximity. The HC carbonate site was rich in
      gamma-Proteobacteria and had a high copy number of mxaF (7.1 x 10(6) copies/g
      [wet weight]) and a much lower copy number of the pmoA gene (3.2 x 10(2) copies/g
      [wet weight]). The mmoX gene was never detected. In contrast, the reference core
      contained familiar sequences of marine sedimentary archaeal and bacterial groups
      but not groups specific to C1 metabolism. Geochemical characterization of the
      amounts and isotopic composition of pore water methane and sulfate strongly
      supported the notion that in this zone both aerobic methane oxidation and
      anaerobic methane oxidation, as well as methanogenesis, occur.

PMID- 15574948
TI  - Shedding patterns of verocytotoxin-producing Escherichia coli strains in a cohort
      of calves and their dams on a Scottish beef farm.
AB  - Rectal fecal samples were taken once a week from 49 calves on the same farm. In
      addition, the dams of the calves were sampled at the time of calf birth and at
      the end of the study. Strains of verocytotoxin-producing Escherichia coli (VTEC)
      were isolated from these samples by using PCR and DNA probe hybridization tests
      and were characterized with respect to serotype, verocytotoxin gene (vtx) type,
      and the presence of the intimin (eae) and hemolysin (ehxA) genes. A total of 170
      VTEC strains were isolated during 21 weeks from 130 (20%) of 664 samples from
      calves and from 40 (47%) of 86 samples from their dams. The characteristics of
      the calf strains differed from those strains isolated from the dams with respect
      to verocytotoxin 2 and the presence of the eae gene. In addition, no calf shed
      the same VTEC serogroup (excluding O?) as its dam at birth or at the end of the
      study. The most frequently detected serogroups in calves were serogroup O26 and
      provisional serogroup E40874 (VTEC O26 was found in 25 calves), whereas in dams
      serogroup O91 and provisional serogroup E54071 were the most common serogroups.
      VTEC O26 shedding appeared to be associated with very young calves and declined
      as the calves aged, whereas VTEC O2 shedding was associated with housing of the
      animals. VTEC O26 strains from calves were characterized by the presence of the
      vtx1, eae, and ehxA genes, whereas vtx2 was associated with VTEC O2 and
      provisional serogroup E40874. The high prevalence of VTEC O26 and of VTEC strains
      harboring the eae gene in this calf cohort is notable because of the association
      of the O26 serogroup and the presence of the eae gene with human disease. No
      association between calf diarrhea and any of the VTEC serogroups was identified.

PMID- 15574949
TI  - Cyclo(L-leucyl-L-prolyl) produced by Achromobacter xylosoxidans inhibits
      aflatoxin production by Aspergillus parasiticus.
AB  - Aflatoxins are potent carcinogenic and toxic substances that are produced
      primarily by Aspergillus flavus and Aspergillus parasiticus. We found that a
      bacterium remarkably inhibited production of norsolorinic acid, a precursor of
      aflatoxin, by A. parasiticus. This bacterium was identified as Achromobacter
      xylosoxidans based on its 16S ribosomal DNA sequence and was designated A.
      xylosoxidans NFRI-A1. A. xylosoxidans strains commonly showed similar inhibition.
      The inhibitory substance(s) was excreted into the medium and was stable after
      heat, acid, or alkaline treatment. Although the bacterium appeared to produce
      several inhibitory substances, we finally succeeded in purifying a major
      inhibitory substance from the culture medium using Diaion HP20 column
      chromatography, thin-layer chromatography, and high-performance liquid
      chromatography. The purified inhibitory substance was identified as cyclo(L
      leucyl-L-prolyl) based on physicochemical methods. The 50% inhibitory
      concentration for aflatoxin production by A. parasiticus SYS-4 (= NRRL2999) was
      0.20 mg ml(-1), as determined by the tip culture method. High concentrations
      (more than 6.0 mg ml(-1)) of cyclo(L-leucyl-L-prolyl) further inhibited fungal
      growth. Similar inhibitory activities were observed with cyclo(D-leucyl-D-prolyl)
      and cyclo(L-valyl-L-prolyl), whereas cyclo(D-prolyl-L-leucyl) and cyclo(L-prolyl
      D-leucyl) showed weaker activities. Reverse transcription-PCR analyses showed
      that cyclo(L-leucyl-L-prolyl) repressed transcription of the aflatoxin-related
      genes aflR, hexB, pksL1, and dmtA. This is the first report of a cyclodipeptide
      that affects aflatoxin production.

PMID- 15574950
TI  - Effects of climate on incidence of Campylobacter spp. in humans and prevalence in
      broiler flocks in Denmark.
AB  - Campylobacter infections are increasing and pose a serious public health problem
      in Denmark. Infections in humans and broiler flocks show similar seasonality,
      suggesting that climate may play a role in infection. We examined the effects of
      temperature, precipitation, relative humidity, and hours of sunlight on
      Campylobacter incidence in humans and broiler flocks by using lag dependence
      functions, locally fitted linear models, and cross validation methods. For
      humans, the best model included average temperature and sunlight 4 weeks prior to
      infection; the maximum temperature lagged at 4 weeks was the best single
      predictor. For broilers, the average and maximum temperatures 3 weeks prior to
      slaughter gave the best estimate; the average temperature lagged at 3 weeks was
      the best single predictor. The combined effects of temperature and sunlight or
      the combined effects of temperature and relative humidity predicted the incidence
      in humans equally well. For broiler flock incidence these factors explained
      considerably less. Future research should focus on elements within the broiler
      environment that may be affected by climate, as well as the interaction of
      microclimatic factors on and around broiler farms. There is a need to quantify
      the contribution of broilers as a source of campylobacteriosis in humans and to
      further examine the effect of temperature on human incidence after this
      contribution is accounted for. Investigations should be conducted into food
      consumption and preparation practices and poultry sales that may vary by season.

PMID- 15574951
TI  - Viable but nonculturable Vibrio cholerae O1 in the aquatic environment of
      Argentina.
AB  - In Argentina, as in other countries of Latin America, cholera has occurred in an
      epidemic pattern. Vibrio cholerae O1 is native to the aquatic environment, and it
      occurs in both culturable and viable but nonculturable (VNC) forms, the latter
      during interepidemic periods. This is the first report of the presence of VNC V.
      cholerae O1 in the estuarine and marine waters of the Rio de la Plata and the
      Argentine shelf of the Atlantic Ocean, respectively. Employing immunofluorescence
      and PCR methods, we were able to detect reservoirs of V. cholerae O1 carrying the
      virulence-associated genes ctxA and tcpA. The VNC forms of V. cholerae O1 were
      identified in samples of water, phytoplankton, and zooplankton; the latter
      organisms were mainly the copepods Acartia tonsa, Diaptomus sp., Paracalanus
      crassirostris, and Paracalanus parvus. We found that under favorable conditions,
      the VNC form of V. cholerae can revert to the pathogenic, transmissible state. We
      concluded that V. cholerae O1 is a resident of Argentinean waters, as has been
      shown to be the case in other geographic regions of the world.

PMID- 15574952
TI  - Novel, attached, sulfur-oxidizing bacteria at shallow hydrothermal vents possess
      vacuoles not involved in respiratory nitrate accumulation.
AB  - Novel, vacuolate sulfur bacteria occur at shallow hydrothermal vents near White
      Point, Calif. There, these filaments are attached densely to diverse biotic and
      abiotic substrates and extend one to several centimeters into the surrounding
      environment, where they are alternately exposed to sulfidic and oxygenated
      seawater. Characterizations of native filaments collected from this location
      indicate that these filaments possess novel morphological and physiological
      properties compared to all other vacuolate bacteria characterized to date.
      Attached filaments, ranging in diameter from 4 to 100 microm or more, were
      composed of cylindrical cells, each containing a thin annulus of sulfur globule
      filled cytoplasm surrounding a large central vacuole. A near-complete 16S rRNA
      gene sequence was obtained and confirmed by fluorescent in situ hybridization to
      be associated only with filaments having a diameter of 10 microm or more.
      Phylogenetic analysis indicates that these wider, attached filaments form within
      the gamma proteobacteria a monophyletic group that includes all previously
      described vacuolate sulfur bacteria (the genera Beggiatoa, Thioploca, and
      Thiomargarita) and no nonvacuolate genera. However, unlike for all previously
      described vacuolate bacteria, repeated measurements of cell lysates from samples
      collected over 2 years indicate that the attached White Point filaments do not
      store internal nitrate. It is possible that these vacuoles are involved in
      transient storage of oxygen or contribute to the relative buoyancy of these
      filaments.

PMID- 15574953
TI  - Complete nucleotide sequence of the conjugative tetracycline resistance plasmid
      pFBAOT6, a member of a group of IncU plasmids with global ubiquity.
AB  - This study presents the first complete sequence of an IncU plasmid, pFBAOT6. This
      plasmid was originally isolated from a strain of Aeromonas caviae from hospital
      effluent (Westmorland General Hospital, Kendal, United Kingdom) in September 1997
      (G. Rhodes, G. Huys, J. Swings, P. McGann, M. Hiney, P. Smith, and R. W. Pickup,
      Appl. Environ. Microbiol. 66:3883-3890, 2000) and belongs to a group of related
      plasmids with global ubiquity. pFBAOT6 is 84,748 bp long and has 94 predicted
      coding sequences, only 12 of which do not have a possible function that has been
      attributed. Putative replication, maintenance, and transfer functions have been
      identified and are located in a region in the first 31 kb of the plasmid. The
      replication region is poorly understood but exhibits some identity at the protein
      level with replication proteins from the gram-positive bacteria Bacillus and
      Clostridium. The mating pair formation system is a virB homologue, type IV
      secretory pathway that is similar in its structural organization to the mating
      pair formation systems of the related broad-host-range (BHR) environmental
      plasmids pIPO2, pXF51, and pSB102 from plant-associated bacteria. Partitioning
      and maintenance genes are homologues of genes in IncP plasmids. The DNA transfer
      genes and the putative oriT site also exhibit high levels of similarity with
      those of plasmids pIPO2, pXF51, and pSB102. The genetic load region encompasses
      54 kb, comprises the resistance genes, and includes a class I integron, an IS630
      relative, and other transposable elements in a 43-kb region that may be a novel
      Tn1721-flanked composite transposon. This region also contains 24 genes that
      exhibit the highest levels of identity to chromosomal genes of several plant
      associated bacteria. The features of the backbone of pFBAOT6 that are shared with
      this newly defined group of environmental BHR plasmids suggest that pFBAOT6 may
      be a relative of this group, but a relative that was isolated from a clinical
      bacterial environment rather than a plant-associated bacterial environment.

PMID- 15574954
TI  - Construction and characterization of a highly efficient Francisella shuttle
      plasmid.
AB  - Francisella tularensis is a facultative intracellular pathogen that infects a
      wide variety of mammals and causes tularemia in humans. It is recognized as a
      potential agent of bioterrorism due to its low infectious dose and multiple
      routes of transmission. To date, genetic manipulation in Francisella spp. has
      been limited due to the inefficiency of DNA transformation, the relative lack of
      useful selective markers, and the lack of stably replicating plasmids. Therefore,
      the goal of this study was to develop an enhanced shuttle plasmid that could be
      utilized for a variety of genetic procedures in both Francisella and Escherichia
      coli. A hybrid plasmid, pFNLTP1, was isolated that was transformed by
      electroporation at frequencies of >1 x 10(7) CFU mug of DNA(-1) in F. tularensis
      LVS, Francisella novicida U112, and E. coli DH5alpha. Furthermore, this plasmid
      was stably maintained in F. tularensis LVS after passage in the absence of
      antibiotic selection in vitro and after 3 days of growth in J774A.1 macrophages.
      Importantly, F. tularensis LVS derivatives carrying pFNLTP1 were unaltered in
      their growth characteristics in laboratory medium and macrophages compared to
      wild-type LVS. We also constructed derivatives of pFNLTP1 containing expanded
      multiple cloning sites or temperature-sensitive mutations that failed to allow
      plasmid replication in F. tularensis LVS at the nonpermissive temperature. In
      addition, the utility of pFNLTP1 as a vehicle for gene expression, as well as
      complementation, was demonstrated. In summary, we describe construction of a
      Francisella shuttle plasmid that is transformed at high efficiency, is stably
      maintained, and does not alter the growth of Francisella in macrophages. This new
      tool should significantly enhance genetic manipulation and characterization of F.
      tularensis and other Francisella biotypes.

PMID- 15574955
TI  - Isolation and characterization of novel marine-derived actinomycete taxa rich in
      bioactive metabolites.
AB  - A unique selective enrichment procedure has resulted in the isolation and
      identification of two new genera of marine-derived actinobacteria. Approximately
      90% of the microorganisms cultured by using the presented method were from the
      prospective new genera, a result indicative of its high selectivity. In this
      study, 102 actinomycetes were isolated from subtidal marine sediments collected
      from the Bismarck Sea and the Solomon Sea off the coast of Papua New Guinea. A
      combination of physiological parameters, chemotaxonomic characteristics,
      distinguishing 16S rRNA gene sequences, and phylogenetic analysis based on 16S
      rRNA genes provided strong evidence for the two new genera (represented by
      strains of the PNG1 clade and strain UMM518) within the family
      Micromonosporaceae. Biological activity testing of fermentation products from the
      new marine-derived actinomycetes revealed that several had activities against
      multidrug-resistant gram-positive pathogens, malignant cells, and vaccinia virus
      replication.

PMID- 15574956
TI  - Analysis of proteasome-dependent proteolysis in Haloferax volcanii cells, using
      short-lived green fluorescent proteins.
AB  - Proteasomes are energy-dependent proteases that are central to the quality
      control and regulated turnover of proteins in eukaryotic cells. Dissection of
      this proteolytic pathway in archaea, however, has been hampered by the lack of
      substrates that are easily detected in whole cells. In the present study, we
      developed a convenient reporter system by functional expression of a green
      fluorescent protein variant with C-terminal fusions in the haloarchaeon Haloferax
      volcanii. The levels of this reporter protein correlated with whole-cell
      fluorescence that was readily detected in culture. Accumulation of the reporter
      protein was dependent on the sequence of the C-terminal amino acid fusion, as
      well as the presence of an irreversible, proteasome-specific inhibitor (clasto
      lactacystin beta-lactone). This inhibitor was highly specific for H. volcanii 20S
      proteasomes, with a Ki of approximately 40 nM. In contrast, phenylmethanesulfonyl
      fluoride did not influence the levels of fluorescent reporter protein or inhibit
      20S proteasomes. Together, these findings provide a powerful tool for the
      elucidation of protein substrate recognition motifs and the identification of new
      genes which may be involved in the proteasome pathway of archaea.

PMID- 15574957
TI  - Nucleotide sequences, genetic organization, and distribution of pEU30 and pEL60
      from Erwinia amylovora.
AB  - The nucleotide sequences, genetic organization, and distribution of plasmids
      pEU30 (30,314 bp) and pEL60 (60,145 bp) from the plant pathogen Erwinia amylovora
      are described. The newly characterized pEU30 and pEL60 plasmids inhabited strains
      isolated in the western United States and Lebanon, respectively. The gene content
      of pEU30 resembled plasmids found in plant-associated bacteria, while that of
      pEL60 was most similar to IncL/M plasmids inhabiting enteric bacteria.

PMID- 15574958
TI  - Reevaluation and reduction of a PCR bias caused by reannealing of templates.
AB  - We reevaluated the bias toward a 1:1 ratio of products in multitemplate PCR used
      in ecological studies and showed that the template reannealing at the annealing
      step would not cause the bias; however, the preferential homoduplex formation
      during temperature decrease from denaturation to annealing step would cause the
      bias.

PMID- 15574959
TI  - Flow cytometry-assisted cloning of specific sequence motifs from complex 16S rRNA
      gene libraries.
AB  - A flow cytometry method was developed for rapid screening and recovery of cloned
      DNA containing common sequence motifs. This approach, termed fluorescence
      activated cell sorting-assisted cloning, was used to recover sequences affiliated
      with a unique lineage within the Bacteroidetes not abundant in a clone library of
      environmental 16S rRNA genes.

PMID- 15574960
TI  - Role for compatible solutes glycine betaine and L-carnitine in listerial
      barotolerance.
AB  - Increased listerial barotolerance at elevated osmolarity is attributed, in part,
      to the presence of accumulated betaine and L-carnitine. The percentage of
      listerial survival following exposure to 400 MPa for 5 min increased from 0.008
      to 0.02% with added L-carnitine (5 mM) and to 0.05% with added betaine (5 mM).
      Furthermore, listerial cells incapable of transporting compatible solutes fail to
      adapt to high pressure at elevated osmolarity.

PMID- 15574961
TI  - Resistance of solid-phase U(VI) to microbial reduction during in situ
      bioremediation of uranium-contaminated groundwater.
AB  - Speciation of solid-phase uranium in uranium-contaminated subsurface sediments
      undergoing uranium bioremediation demonstrated that although microbial reduction
      of soluble U(VI) readily immobilized uranium as U(IV), a substantial portion of
      the U(VI) in the aquifer was strongly associated with the sediments and was not
      microbially reducible. These results have important implications for in situ
      uranium bioremediation strategies.

PMID- 15574962
TI  - Effects of expression of hemA and hemB genes on production of porphyrin in
      Propionibacterium freudenreichii.
AB  - The genus Propionibacterium has a wide range of probiotic activities that are
      exploited in dairy and fermentation systems such as cheeses, propionic acid, and
      tetrapyrrole compounds. In order to improve production of tetrapyrrole compounds,
      we expressed the hemA gene, which encodes delta-aminolevulinic acid (ALA)
      synthase from Rhodobacter sphaeroides, and the hemB gene, which encodes
      porphobilinogen (PBG) synthase from Propionibacterium freudenreichii subsp.
      shermanii IFO12424, either monocistronically or polycistronically in strain
      IFO12426. The recombinant strains accumulated larger amounts of ALA and PBG, with
      resultant 28- to 33-fold-higher production of porphyrinogens, such as
      uroporphyrinogen and coproporphyrinogen, than those observed in strain IFO12426,
      which harbored the shuttle vector pPK705.

PMID- 15574963
TI  - A previously unexposed forest soil microbial community degrades high levels of
      the pollutant 2,4,6-trichlorophenol.
AB  - 2,4,6-trichlorophenol (2,4,6-TCP) is a hazardous pollutant that is efficiently
      degraded by some aerobic soil bacterial isolates under laboratory conditions. The
      degradation of this pollutant in soils and its effect on the soil microbial
      community are poorly understood. We report here the ability of a previously
      unexposed forest soil microbiota to degrade high levels of 2,4,6-TCP and describe
      the changes in the soil microbial community found by terminal restriction
      fragment length polymorphism (T-RFLP) analysis. After 30 days of incubation,
      about 50% degradation of this pollutant was observed in soils amended with 50 to
      5,000 ppm of 2,4,6-TCP. The T-RFLP analysis showed that the soil bacterial
      community was essentially unchanged after exposure to up to 500 ppm of 2,4,6-TCP.
      However, a significant decrease in richness was found with 2,000 and 5,000 ppm of
      2,4,6-TCP, even though the removal of this pollutant remained high. The
      introduction of Ralstonia eutropha JMP134 or R. eutropha MS1, two efficient 2,4,6
      TCP degraders, to this soil did not improve degradation of this pollutant,
      supporting the significant bioremediation potential of this previously unexposed,
      endogenous forest soil microbial community.

PMID- 15574964
TI  - Diversity of nontuberculoid Mycobacterium species in biofilms of urban and
      semiurban drinking water distribution systems.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous and have been isolated from a
      variety of environmental sources, including water. Various NTM were isolated from
      biofilms in drinking water distribution systems in two urban and two semiurban
      areas in South Africa. Most of the isolates belonged to opportunistic pathogenic
      species of the NTM group, but none belonged to the Mycobacterium avium complex.

PMID- 15574965
TI  - Genotypes of Cryptosporidium species infecting fur-bearing mammals differ from
      those of species infecting humans.
AB  - Of 471 specimens examined from foxes, raccoons, muskrats, otters, and beavers
      living in wetlands adjacent to the Chesapeake Bay, 36 were positive for five
      types of Cryptosporidium, including the C. canis dog and fox genotypes,
      Cryptosporidium muskrat genotypes I and II, and Cryptosporidium skunk genotype.
      Thus, fur-bearing mammals in watersheds excreted host-adapted Cryptosporidium
      oocysts that are not known to be of significant public health importance.

PMID- 15574966
TI  - Association of Escherichia coli O157:H7 with houseflies on a cattle farm.
AB  - The ecology of Escherichia coli O157:H7 is not well understood. The aims of this
      study were to determine the prevalence of and characterize E. coli O157:H7
      associated with houseflies (HF). Musca domestica L. HF (n = 3,440) were collected
      from two sites on a cattle farm over a 4-month period and processed individually
      for E. coli O157:H7 isolation and quantification. The prevalence of E. coli
      O157:H7 was 2.9 and 1.4% in HF collected from feed bunks and a cattle feed
      storage shed, respectively. E. coli O157:H7 counts ranged from 3.0 x 10(1) to 1.5
      x 10(5) CFU among the positive HF. PCR analysis of the E. coli O157:H7 isolates
      revealed that 90.4, 99.2, 99.2, and 100% of them (n = 125) possessed the stx1,
      stx2, eaeA, and fliC genes, respectively. Large populations of HF on cattle farms
      may play a role in the dissemination of E. coli O157:H7 among animals and to the
      surrounding environment.

PMID- 15574967
TI  - Towards a strategic plan for research to support the global program to eliminate
      lymphatic filariasis. Summary of Immediate needs and opportunities for research
      on lymphatic filariasis. Philadelphia, Pennsylvania, USA, December 9-10, 2003.

PMID- 15574984
TI  - Harmonisation of individual monitoring in Europe.

PMID- 15574985
TI  - Implementation of standards for individual monitoring in Europe.
AB  - A large number of standards are available for radiation protection and individual
      monitoring purposes. They are published by various organisations, international
      and national. Moreover, the increasing policy of "Quality" applied to individual
      monitoring requires the implementation of standards on Quality Assurance (QA)
      both in technical and management aspects of a dosimetric service. Implementation
      of standards is not mandatory; therefore, varying degrees of implementation can
      be found in different European countries. However, for a number of good reasons,
      a degree of harmonisation within the European Union (EU) of the requirements and
      procedures for individual monitoring would be desirable. Harmonisation as applied
      to dosimetric services does not mean that they should all follow exactly the same
      procedures, but that they should aim to meet the same general requirements, and
      their results should be comparable. This article aims to compile information on
      the use of all standards applied within individual monitoring practices, be it on
      the calibration of dosemeters or on the QA procedures to be applied to the
      overall dose evaluation process. Both "technical standards" and "quality
      standards" will be discussed. A list of documents of relevance to subjects such
      as recommendations and requirements in the field of individual monitoring, whose
      application could help in the harmonisation of procedures, will also be given. As
      it is agreed that implementation of quality standards is a relevant framework
      within which harmonisation can be achieved, guidance on the implementation of
      quality standards in a dosimetric service is given. Accreditation and approval of
      dosimetric services will be of relevance in the process of harmonisation of
      individual monitoring within the EU. In this article, a discussion of various
      procedures and the meaning of both forms of recognition is also provided.
      Although most of the text applies to the monitoring of internal and external
      exposure to ionising radiation, the emphasis of this practical guidance is on
      monitoring for external radiation with passive dosemeters.

PMID- 15574986
TI  - A catalogue of dosemeters and dosimetric services within Europe--an update.
AB  - The catalogue of dosemeters and dosimetric services within the European Union
      (EU) Member States and Switzerland that was issued by EURADOS in the year 2000
      has been updated and extended with information on dosimetric services in the new
      EU Member States and Bulgaria, Croatia, Romania, Serbia and Montenegro, and
      Ukraine. The total number of dosimetric services in these European countries is
      now estimated to be about 200. The present catalogue is based on information
      collected from 90 European dosimetric services, among which 34 questionnaires
      from 32 services were obtained over the years 2001-2004 for the first time. This
      article assesses and updates the present use of personal dosemeters and the
      extent to which occupationally exposed persons in Europe are monitored with
      dosemeters able to measure the operational quantity-personal dose equivalent,
      H(P)(d). The perspective of joining EU by the new countries accelerated the
      implementation of the EU Basic Safety Standard Directive to their national
      regulations. As a result, all newly investigated services reported their ability
      to measure H(P)(d). The catalogue provides information on the dosemeters, dose
      calculation and background subtraction algorithms, calibration methods, energy
      and angular response, and performance.

PMID- 15574987
TI  - Individual monitoring for internal exposure in Europe and the integration of
      dosimetric data.
AB  - The European Radiation Dosimetry Group, EURADOS, established a working group
      consisting of experts whose aim is to assist in the process of harmonisation of
      individual monitoring as part of the protection of occupationally exposed
      workers. A catalogue of facilities and internal dosimetric techniques related to
      individual monitoring in Europe has been completed as a result of this EURADOS
      study. A questionnaire was sent in 2002 to services requesting information on
      various topics including type of exposures, techniques used for direct and
      indirect measurements including calibration and sensitivity data and the methods
      employed for the assessment of internal doses. Information relating to Quality
      Control procedures for direct and indirect measurements, Quality Assurance
      Programmes in the facilities and legal requirements for "approved dosimetric
      services" were also considered. A total of 71 completed questionnaires were
      returned by internal dosimetry facilities in 26 countries. This results in an
      overview of the actual status of the processes used in internal exposure
      estimation in Europe. In many ways harmonisation is a reality in internal dose
      assessments, especially when taking into account the measurements of the activity
      retained or excreted from the body. However, a future study detailing the
      estimation of minimum detectable activity in the laboratories is highly
      recommended. Points to focus on in future harmonisation activities are as
      follows: the process of calculation of doses from measured activity,
      establishment of guidelines, similar dosimetric tools and application of the same
      ICRP recommendations. This would lead to a better and more harmonised approach to
      the estimation of internal exposures in all European facilities.

PMID- 15574988
TI  - Workplace monitoring for exposures to radon and to other natural sources in
      Europe: integration of monitoring for internal and external exposures.
AB  - Part of the action of the EURADOS working group (European Radiation Dosimetry
      Group) on "Harmonisation of Individual Monitoring in Europe" was to investigate
      how the results from personal dosemeters for external radiation, from monitoring
      for internal exposure and from workplace monitoring, can be combined into a
      complete and consistent system of individual monitoring. To facilitate this work,
      the "EURADOS questionnaire Q3" relating to radon and other natural sources of
      radiation in the workplace was distributed to relevant institutes across Europe.
      A total of 24 countries replied to the questionnaire. This study offers an
      important overview on actual regulations, national standards and reference levels
      for protection of employees from radon and other natural sources in different
      workplace scenarios. Information was also collected on individual monitoring and
      area monitoring to determine individual doses in workplaces with elevated levels
      of natural radiation. The article discusses in detail the results obtained
      showing by country the reference level in workplaces for radon gas and other
      natural sources. In both instances, exposures in mines, other underground
      workplaces, industry workplaces/waterworks, offices, schools and day-care homes
      were considered. The resultant data clearly indicate that there is a need for
      harmonisation among countries, not least in the areas of regulation and use of
      reference levels in the workplace.

PMID- 15574989
TI  - Active personal dosemeters for individual monitoring and other new developments.
AB  - In this paper, we will present a first (but not complete) status description of
      active personal dosemeters (APDs) and their implementation in European countries.
      In modern radiation protection practices, APDs are becoming absolutely necessary
      operational tools for satisfying the ALARA principle. Despite their success, they
      are relatively new for individual monitoring of workers. Regulation, legal
      requirements and calibration procedures are different in European member states.
      A catalogue of commercially available and prototype devices is presented.
      Improvement on devices and in implementation of calibration method are expected
      in the forthcoming years. End-user feedback experience and requirements are
      reported.

PMID- 15574990
TI  - Quality control and reliability of reported doses.
AB  - Results of performance tests verifying the dosimetric properties of dosimetric
      systems are published in various reports (e.g. IAEA and EURADOS). However, there
      is hardly any information in the open literature relating to the uncertainty in a
      dose measurement or in the annual dose, which is increased by failure of the
      evaluation or data management system, damage of the dosemeter itself or by the
      loss of dosemeter. In this article, an attempt is made to estimate the importance
      of the above-mentioned conditions. This is achieved by sending questionnaires to
      about 200 approved dosimetric services in Europe. In total 88 questionnaires were
      returned and analysed. In the questionnaires, the frequency of occurrence of the
      various error conditions were investigated. Participants were also asked to
      evaluate the impact of the error condition from a dosimetric point of view and
      what countermeasures are taken. The article summarises all responses and compares
      different sources of errors according to their impact on the uncertainty of the
      resulting dose and gives a comprehensive overview on quality control actions and
      reliability on reported doses from European dosimetric services.

PMID- 15574992
TI  - Renal transplantation 2004: where do we stand today?
AB  - In spite of considerable progress in immunosuppressive and supportive treatment,
      numerous problems persist which interfere with the success of renal
      transplantation. Before transplantation has been performed, factors impacting on
      outcome include the donor (living vs cadaver, age and HLA system) as well as the
      recipient (age, immunological reactivity, potential sensitization and duration of
      dialysis). These are the main factors that affect the outcome of the transplant,
      particularly in the long-term. After transplantation a number of events may put
      graft function at risk: potential recurrence of the primary renal disease in the
      allograft; 'de novo' renal disease triggered by infections, drugs or
      autoimmunity; and non-specific progression promoters, such as diabetes,
      hypertension, proteinuria, nephrotoxic agents and/or viral infections. The two
      most frequent causes of chronic allograft dysfunction are (i) chronic rejection
      (often triggered by preceding acute rejection, delayed graft function or poor
      compliance) and (ii) calcineurin-inhibitor nephrotoxicity (more likely to develop
      in kidneys of older donors or in marginal kidneys). The differential diagnosis
      between these two entities is generally difficult, but some histological clues
      (reduplication of glomerular basement membrane, obliterating vasculopathy and C4d
      deposits) as well as the demonstration of humoral antibodies are pointers
      suggesting rejection. Treatment of chronic graft dysfunction is difficult,
      whatever the cause, particularly in cases with advanced renal lesions. Therefore,
      early diagnosis is of paramount importance. In this regard, graft biopsy can be
      of great help. In spite of many problems and complications, not only short-term
      but also long-term results of renal transplantation are improving progressively,
      as documented by CTS data showing that in Europe for transplants performed
      between 1982 and 1984 the mean graft half-life was 7 years, while for transplants
      performed between 1997 and 1999 it was 20 years.

PMID- 15574993
TI  - Cardiovascular disease in renal patients--a matter of stem cells?

PMID- 15574994
TI  - Don't forget the defibrillator in the dialysis unit.

PMID- 15574995
TI  - Nephrology and renal replacement therapy in Romania--transition still continues
      (Cinderella story revisited).
AB  - INTRODUCTION. This report describes the current status of nephrology and renal
      replacement therapy (RRT) in Romania, a country with previously limited
      facilities, highlighting national changes in the European context. METHODS:
      Trends in RRT development were analysed in 2003, on a national basis, using the
      same questionnaires as in previous surveys (1991, 1995). Survival data and
      prognostic risk factors were calculated retrospectively from a large
      representative sample of 2284 patients starting RRT between January 1, 1995 and
      December 31, 2001 (44% of the total RRT population investigated). RESULTS: In
      2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250
      p.m.p.) were six and five times higher, respectively, than in 1995. The annual
      rate of increase in the stock of RRT patients (11%) was supported mainly by an
      exponential development of the continuous ambulatory peritoneal dialysis (CAPD)
      population (+600%), while the haemodialysis (HD) growth rate was stable (+33%)
      and renal transplantation made a marginal contribution. Renal care infrastructure
      followed the same trend: nephrology departments (+100%) and nephrologists
      (+205%). The characteristics of RRT incident patients changed accordingly to
      current European epidemiology (increasing age and prevalence of diabetes and
      nephroangiosclerosis). The estimated overall survival of RRT patients in Romania
      was 90.6% at 1 year [confidence interval (CI) 89.4-91.8] and 62.2% at 5 years (CI
      59.4-65.0). Patients' survival was negatively influenced (Cox regression
      analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a
      nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of
      erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g.
      cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001,
      HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in
      1996-2003 in Romania was the highest in Europe, the prevalence remained below the
      European mean. As CAPD had the greatest expansion, followed by HD, an effective
      transplantation programme must be set up to overcome the imbalance. The quality
      of RRT appears to be good and survival was similar to that in other registries.
      Further evolution implies strategies of prevention, based on national surveys,
      supported by the Romanian Renal Registry.

PMID- 15574996
TI  - Macrophages in streptozotocin-induced diabetic nephropathy: potential role in
      renal fibrosis.
AB  - BACKGROUND: Renal fibrosis is central to the progression of diabetic nephropathy;
      however, the mechanisms responsible for fibroblast and matrix accumulation in
      this disease are only partially understood. Macrophages accumulate in diabetic
      kidneys, but it is unknown whether macrophages contribute to renal fibrosis.
      Therefore, we examined whether macrophage accumulation is associated with the
      progression of renal injury and fibrosis in type 1 diabetic nephropathy and
      whether macrophages exposed to the diabetic milieu could promote fibroblast
      proliferation. METHODS: Kidney macrophages, renal injury and fibrosis were
      analysed in diabetic C57BL/6J mice at 2, 8, 12 and 18 weeks after streptozotocin
      injection. Isolated rat bone marrow macrophages were stimulated with diabetic rat
      serum or carboxymethyllysine (CML)-bovine serum albumin (BSA) to determine
      whether macrophage-conditioned medium could promote the proliferation of rat
      renal (NRK-49F) fibroblasts. RESULTS: Progressive injury and fibrosis in diabetic
      nephropathy was associated with increased numbers of kidney macrophages.
      Macrophage accumulation in diabetic mice correlated with hyperglycaemia (blood
      glucose, HbA1c levels), renal injury (albuminuria, plasma creatinine),
      histological damage and renal fibrosis (myofibroblasts, collagen IV). Culture
      supernatant derived from bone marrow macrophages incubated with diabetic rat
      serum or CML-BSA induced proliferation of fibroblasts, which was inhibited by pre
      treating fibroblasts with interleukin-1 (IL-1) receptor antagonist or the
      platelet-derived growth factor (PDGF) receptor kinase inhibitor, STI-571.
      CONCLUSION: Kidney macrophage accumulation is associated with the progression of
      renal injury and fibrosis in streptozotocin-induced mouse diabetic nephropathy.
      Elements of the diabetic milieu can stimulate macrophages to promote fibroblast
      proliferation via IL-1- and PDGF-dependent pathways which may enhance renal
      fibrosis.

PMID- 15574997
TI  - Important role for macrophages in induction of crescentic anti-GBM
      glomerulonephritis in WKY rats.
AB  - BACKGROUND: A crucial role for CD8(+) cells in induction of crescentic anti
      glomerular basement membrane (GBM) glomerulonephritis (GN) in WKY rats was
      demonstrated in studies showing that depletion of CD8(+) cells completely
      suppressed glomerular accumulation of monocytes/macrophages (Mo/Mphi), crescent
      formation and proteinuria. Because these studies did not definitively identify
      CD8(+) cells as the cause of tissue injury, we examined the roles of Mo/Mphi in
      the development of anti-GBM GN. METHODS: We examined correlations between the
      amount of urinary protein and the numbers of glomerular CD8(+) cells or Mo/Mphi
      in rats after administrating different doses of anti-GBM antibody (5.0, 7.5, 10.0
      and 25.0 microl/100 g body weight). The roles of Mo/Mphi in induction of GN were
      examined in animals by depleting Mo/Mphi in the glomerulus. To do this, rats were
      injected intravenously with liposome-encapsulated dichloromethylene diphosphonate
      (liposome-MDP) from day 3 to day 7 after anti-GBM antibody injection and they
      were then sacrificed at day 8. RESULTS: Liposome-MDP treatment significantly
      reduced the number of ED-1(+) Mo/Mphi accumulated in glomeruli from 32.1 +/- 1.2
      to 1.4 +/- 0.3/glomerular cross-section (mean +/- SD, P < 0.01), and the amount
      of urinary protein from 103.8 +/- 19.8 to 31.8 +/- 15.9 mg/day (P < 0.01), as
      well as the incidence of crescentic glomeruli from 91.3 +/- 2.7 to 23.3 +/- 7.6%
      (P < 0.01) at day 8. This treatment also reduced the number of CD8(+) cells
      accumulating in the glomeruli from 5.4 +/- 0.7 to 0.5 +/- 0.1/glomerular cross
      section (P < 0.01). Upregulation of glomerular intercellular adhesion molecule 1
      (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was
      suppressed by Mo/Mphi depletion. CONCLUSION: These results indicate that Mo/Mphi
      play an important role in the induction of crescentic anti-GBM GN and glomerular
      injury.

PMID- 15574998
TI  - Candesartan reduced advanced glycation end-products accumulation and diminished
      nitro-oxidative stress in type 2 diabetic KK/Ta mice.
AB  - BACKGROUND: Angiotensin-II induces nitro-oxidative stress in patients with
      diabetic nephropathy. Peroxynitrite and reactive oxide species can accelerate
      formation of advanced glycation end-products (AGEs). We investigated the effects
      of candesartan, an angiotensin-II type 1 receptor blocker (ARB), on the formation
      of AGEs and nitro-oxidative stress in type 2 diabetic KK/Ta mouse kidneys.
      METHODS: KK/Ta mice were divided into three treatment groups: an early treatment
      group receiving 4 mg/kg/day candesartan from 6 to 28 weeks of age, a late
      treatment group receiving the same candesartan dose from 12 to 28 weeks of age
      and a group receiving the vehicle for candesartan. BALB/c mice treated with
      vehicle were used as controls. We evaluated at 28 weeks the renal expressions of
      carboxymethyllysine, the receptor for AGE (RAGE), the p47phox component of NADPH
      oxidase, endothelial nitric oxide synthase (eNOS), induced nitric oxide synthase
      (iNOS) and 8-OHdG and nitrotyrosine by immunohistochemistry and/or by competitive
      RT-PCR. RESULTS: Kidneys from KK/Ta mice showed increased formation of AGEs,
      nitro-oxidative stress and RAGE expression and these were attenuated by
      candesartan treatment. Protein and mRNA expressions of p47phox and iNOS were
      upregulated in KK/Ta kidneys, which also showed increased immunostaining
      intensities of 8-OHdG and nitrotyrosine. Treatment with candesartan attenuated
      all of these changes and prevented significant albuminuria. There were no
      significant differences in the expression of eNOS among the four groups.
      CONCLUSIONS: These findings suggest that candesartan, an ARB, reduces AGE
      accumulation and subsequent albuminuria by down-regulating the NADPH oxidase
      p47phox component and iNOS expression and by attenuating RAGE expression in type
      2 diabetic KK/Ta mouse kidneys.

PMID- 15574999
TI  - The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is
      mediated by an increased apoptosis of Th1 subset.
AB  - BACKGROUND: In uraemia there is a reduction in the total number of T lymphocytes
      and an imbalance in the ratio of Th1/Th2 T-helper (Th) lymphocytes. A higher rate
      of apoptosis in T lymphocytes has been reported in haemodialysis patients. The
      aims of the present study were to assess the Th1/Th2 pattern in uraemia and to
      evaluate whether a relative increase in Th1 apoptosis may explain the Th1/Th2
      imbalance observed in uraemic patients. METHODS: Seventeen non-dialysed uraemic
      patients were evaluated; eight healthy volunteers served as controls.
      Intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured
      by direct intracellular immunofluorescence and flow cytometry. Apoptosis was
      determined by flow cytometry using annexin V or TUNEL. Mechanisms of apoptosis
      were assessed by determination of Fas and Bcl-2 expression. RESULTS: Cell
      production of cytokines is significantly higher in uraemic patients than in
      controls. In addition, in uraemic patients only 5.1+/-2.1% of the T lymphocytes
      contained IFN-gamma (Th1 cells) while 61.9 +/- 14.8% contained IL-4 (Th2 cells)
      (P < 0.0001). The percentage of apoptosis was 29.6 +/- 6.3% and 4.7 +/- 1.6% in
      Th1 and Th2 lymphocytes, respectively (P < 0.001). Fas expression was higher in
      Th1 than in Th2 cells and the expression of Bcl-2 was lower in Th1 than in Th2
      cells. The apoptosis induced by anti-Fas antibodies was similar in both types of
      lymphocytes. CONCLUSIONS: In uraemia there is a reduction in the proportion of
      Th1 lymphocytes due to a higher rate of apoptosis in this subset of lymphocytes.
      Th1 from uraemic patients show a higher expression of Fas and a lower expression
      of Bcl-2 than Th2. This makes uraemic Th1 cells more susceptible to apoptosis.
      The Th1/Th2 imbalance may contribute to alterations in cellular immunity observed
      in chronic kidney disease patients.

PMID- 15575000
TI  - Apoptosis of human polymorphonuclear neutrophils accelerated by dialysis
      membranes via the activation of the complement system.
AB  - BACKGROUND: Haemodialysis (HD) with bioincompatible cellulosic membranes like
      Cuprophan (CU) is considered to influence negatively the clinical outcome of
      acute and chronic renal failure. In this effect, apart from the disturbance of
      phagocytosis or oxygen species production by leukocytes, increased apoptosis also
      has been implicated recently. The objective of this study was to study the effect
      of HD membranes on apoptosis induction in polymorphonuclear neutrophils (PMN).
      METHODS: PMN from healthy donors and uraemic patients were isolated and apoptosis
      was induced by co-incubation with CU, Hemophan or polyamide hollow fibres in the
      presence of serum from healthy or uraemic humans. Apoptosis was quantified by
      flow cytometry using Annexin V-FITC and propidium iodide staining and was
      confirmed by the detection of DNA fragmentation on gel electrophoresis. The
      deposition of immunoglobulins (Ig) and complement factors on hollow fibres was
      detected by direct immunofluorescence. RESULTS: Heat inactivation or the
      depletion of complement components or Ig significantly reduced apoptosis,
      indicating its dependence on classical complement activation. The detection of
      IgG on hollow CU fibres and the restored acceleration of apoptosis by the
      appropriate replenishment of Ig-deficient sera additionally confirmed these
      findings. Inhibition experiments revealed that caspases were necessary mainly,
      but not exclusively, for apoptosis to occur after complement activation. Uraemia
      led to increased PMN apoptosis in the presence of bioincompatible, but not
      biocompatible, membranes. CONCLUSIONS: Our results suggest that the acceleration
      of PMN apoptosis in the presence of CU is mediated via an antibody-dependent
      activation of the classical complement pathway mobilizing both caspase-dependent
      and -independent pathways.

PMID- 15575001
TI  - The effect of isolated ultrafiltration on Doppler-derived indices of left
      ventricular diastolic function.
AB  - BACKGROUND: Haemodialysis (HD) is associated with acute changes simultaneously in
      fluid status (ultrafiltration) and in many biochemical parameters (dialysis).
      Reports on the effects of these changes on left ventricular (LV) diastolic
      function are scant. This study evaluated the effect of isolated ultrafiltration
      (UF) and subsequent HD with minimal fluid removal on Doppler-derived indices of
      LV diastolic function in patients who were asymptomatic and stable on HD.
      METHODS: In 11 HD cases, the 5 h treatment session was divided into a 2.5 h
      period of fluid removal without dialysis (UF phase) and 2.5 h of dialysis with
      minimal fluid removal (HD phase). We examined the following parameters of LV
      diastolic function echocardiographically: early rapid filling (Emax), atrial peak
      filling (Amax), Emax/Amax ratio, isovolumic relaxation time (IVRT) and
      deceleration time of the E-wave (DT). RESULTS: During the UF phase, Emax
      decreased from 0.82 +/- 0.2 to 0.62 +/- 0.2 m/s (P = 0.003), Amax decreased from
      0.72 +/- 0.2 to 0.63 +/- 0.2 m/s (P = 0.042) and the ratio Emax/Amax did not
      change (P = NS). During the HD phase, Emax increased from 0.62 +/- 0.2 to 0.72 +/
      0.2 m/s (P = 0.018), Amax increased from 0.63 +/- 0.2 to 0.70 +/- 0.3 m/s (P =
      NS) and the Emax/Amax ratio remained unchanged (P = NS). IVRT was prolonged in 10
      out of 11 patients at the start of the UF phase and it was further prolonged from
      142 +/- 40 to 171 +/- 55 ms (P = 0.03) during the UF phase. IVRT did not alter
      during the HD phase (P = NS). During the UF phase, DT increased from 175 +/- 83
      to 244 +/- 119 and it decreased from 244+/-119 to 209 +/- 98 in the HD phase, but
      both changes were statistically insignificant. No statistically significant
      correlations were observed between the changes in the Doppler indices of
      diastolic function and changes in biochemical parameters during the HD phase.
      CONCLUSIONS: UF affects the parameters Emax, Amax and IVRT used to evaluate LV
      diastolic function. The changes in Emax and Amax during the HD phase are due to
      fluid refilling from tissues into the blood space, HD as such having no effect on
      Doppler indices. However, isolated UF or HD does not affect the Emax/Amax ratio.
      Emax and IVRT seem to be the most volume-sensitive parameters.

PMID- 15575002
TI  - Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo
      controlled, double-blind trial.
AB  - BACKGROUND: Uraemic pruritus is a common and distressing symptom in patients on
      haemodialysis for chronic renal failure. Gabapentin is an anticonvulsant that
      alleviates neuropathic pain. We conducted a double-blind, placebo-controlled,
      crossover study to assess its effectiveness against renal itch. METHODS: We
      enrolled in the trial 25 adult patients on haemodialysis who were asked to daily
      record the severity of their pruritus on a visual analogue scale. The patients
      were randomly assigned to receive gabapentin for 4 weeks followed by placebo for
      4 weeks or the reverse sequence. Gabapentin or placebo were administered thrice
      weekly, at the end of haemodialysis sessions. RESULTS: The mean pruritus score of
      the cohort before the study was 8.4 +/- 0.94. After placebo intake, it decreased
      to 7.6 +/- 2.6 (P = 0.098). The score of four patients decreased by >50%
      following placebo. After gabapentin administration, the mean score decreased
      significantly, to 1.2 +/- 1.8 (P = 0.0001), although one patient's symptoms did
      not improve significantly. No patient dropped out of the study due to adverse
      effects from gabapentin. CONCLUSIONS: Our study shows that gabapentin is safe and
      effective for treating uraemic pruritus in haemodialysis patients. Our results
      also support the neuropathic hypothesis of uraemic pruritus.

PMID- 15575003
TI  - Functional consequences of a novel uromodulin mutation in a family with familial
      juvenile hyperuricaemic nephropathy.
AB  - BACKGROUND: Familial juvenile hyperuricaemic nephropathy (FJHN) is an autosomal
      dominant disorder featuring hyperuricaemia, low fractional urate excretion,
      interstitial nephritis and chronic renal failure. The responsible gene UMOD was
      recently identified. UMOD encodes for uromodulin or Tamm-Horsfall glycoprotein,
      the most abundant protein in normal urine. We encountered a family with FJHN and
      identified a novel UMOD mutation in exon 6. METHODS: We sequenced the gene in all
      family members, identified the mutation, and verified its presence in the
      affected members. We next performed functional studies of the mutant protein by
      immunofluorescence and FACS analysis on transfected cells. RESULTS: The mutation
      p.C347G (c.1039T > G) results in a conserved cysteine to glycine amino acid
      substitution in the uromodulin zona pellucida (ZP) domain. The cell studies
      showed that the novel uromodulin mutation causes a delay in protein export to the
      plasma membrane due to its retention in the endoplasmic reticulum. CONCLUSIONS:
      We describe the first reported mutation mapping in the ZP uromodulin domain. Our
      data provide further evidence showing why the excretion of uromodulin is reduced
      in this syndrome.

PMID- 15575004
TI  - Acute glomerulonephritis occurring during immunoadsorption with staphylococcal
      protein A column (Prosorba).
AB  - BACKGROUND: Apheresis of patient plasma by immunoadsorption with a staphylococcal
      protein A (SPA) column is used in a variety of autoimmune disorders.
      Leukocytoclastic vasculitis is an uncommon severe complication that can occur
      during immunoadsorption with SPA (Prosorba. METHODS: We report a case of immune
      complex glomerulonephritis occurring during Prosorba immunoabsorption in a
      patient with rheumatoid arthritis (RA). Using a Medline literature search and
      information provided by Cypress Bioscience/Fresenius Hemocare, we review renal
      complications associated with Prosorba immunoadsorption. RESULTS: We identified
      seven additional potential cases of glomerulonephritis (GN) in association with
      Prosorba immunoadsorption. Five of these patients were being treated for RA, and
      two for idiopathic thrombocytopenia purpura (ITP). Renal biopsies were performed
      on four patients, all of whom had evidence of immune complex GN. Among RA
      patients treated with Prosorba, the incidence of GN closely paralleled that of
      leukocytoclastic vasculitis at 1.75%. The presence of leukocytoclastic vasculitis
      was a significant risk factor for the development of GN (relative risk = 75.95,
      CI 7-1869, P = 0.00021). In contrast, among more than 10 000 ITP patients treated
      with Prosorba, there were only two potential cases of GN. The risk of developing
      GN in association with Prosorba immunoadsorption was significantly greater for
      patients with RA than for those with ITP (relative risk = 62.95, CI 10-453, P =
      0.00002). CONCLUSION: This case series highlights the risk of GN among patients
      undergoing SPA immunoadsorption. The development of GN is associated with the
      presence of leukocytoclastic vasculitis. Patients with RA seem to be at
      particular risk.

PMID- 15575005
TI  - The dilemma of diagnosing the cause of hypernatraemia: drinking habits vs
      diabetes insipidus.

PMID- 15575006
TI  - Cerebral vasculitis in a teenager with Goodpasture's syndrome.

PMID- 15575007
TI  - Multiple urinary tract malformations with likely recessive inheritance in a large
      Somalian kindred.

PMID- 15575008
TI  - Renal tubular toxicity of HMG-CoA reductase inhibitors.

PMID- 15575009
TI  - Acute renal failure in SARS patients: more than rhabdomyolysis.

PMID- 15575010
TI  - A dramatic case of calciphylaxis 20 years after kidney transplantation.

PMID- 15575011
TI  - Plasma cell myeloma variant of post-transplant lymphoproliferative disorder in a
      solid organ transplant recipient: a case report.

PMID- 15575012
TI  - Why is a shrunken bladder and a nephrotic kidney an expression of the same
      disease?

PMID- 15575013
TI  - Progression of renal failure without proteinuria in a patient with type 1
      diabetes.

PMID- 15575014
TI  - Bedside stereomicroscopy of renal biopsies may lead to a rapid diagnosis of
      Fabry's disease.

PMID- 15575015
TI  - The haemodynamic response to submaximal exercise during isovolaemic
      haemodialysis.

PMID- 15575016
TI  - Trends in coronary artery calcification in peritoneal dialysis and transplant
      patients.

PMID- 15575017
TI  - Timing of acute renal failure in multiple myeloma: two distinct outcomes?

PMID- 15575018
TI  - Cyclosporin A-induced remission of primary membranous glomerulonephritis in a
      child.

PMID- 15575020
TI  - Post-transplant diabetes mellitus and renal function with tacrolimus: A decade of
      use, a decade of evidence. Foreword.

PMID- 15575021
TI  - Post-transplant diabetes mellitus: the last 10 years with tacrolimus.
AB  - Post-transplant diabetes mellitus (PTDM) is a key risk factor for cardiovascular
      disease, which itself is a leading cause of death with a functioning graft. In a
      published review of the literature on PTDM and immunosuppression, most cases of
      PTDM were diagnosed within the first 3 months post-transplantation. In renal
      transplantation, the type of immunosuppressive regimen accounted for 74% of the
      variability recorded in the 12 month cumulative incidence of PTDM between studies
      (P = 0.0004), with inclusion of corticosteroids and/or high-dose ciclosporin or
      tacrolimus being the main risk factors for development of PTDM. Other key risk
      factors were recipient age and non-white ethnicity. The diabetic potential of any
      immunosuppressive protocol depends on the combination of agents used and the
      corresponding doses. Therefore, we conducted an analysis to investigate the
      impact of different tacrolimus-based regimens employed over the past decade
      together with the time of study initiation on the incidence of PTDM. There was a
      progressive decline in the incidence of PTDM with year of study initiation, from
      20% in the early 1990s to 0-5% most recently. The low incidences of PTDM were
      achieved with those protocols employing lower blood levels of tacrolimus and/or
      corticosteroid elimination. These results emphasize the importance of reducing
      the immunosuppressive medication load and the role of corticosteroids in the
      development of PTDM. Evolving tacrolimus-based immunosuppressive protocols for
      renal transplantation over the last 10 years, particularly in terms of tacrolimus
      dosing and corticosteroid elimination, has led to a reduction in PTDM-related
      morbidity without compromising efficacy.

PMID- 15575022
TI  - Improving long-term renal transplant outcomes with tacrolimus: speculation vs
      evidence.
AB  - Achieving long-term graft survival and optimal patient health are ultimate
      clinical goals in renal transplantation. Many factors negatively impact long-term
      transplant outcomes, including graft rejection, renal dysfunction and increased
      cardiovascular burden. Additionally, glucose metabolism disturbance, also a
      cardiovascular risk factor, influences morbidity and mortality. As such, careful
      consideration of the immunosuppressive strategy and its impact on these factors
      is critical to optimizing outcomes. Large-scale clinical trials and registry
      studies conducted over the past decade have demonstrated tacrolimus to be a
      cornerstone immunosuppressant in renal transplantation. Compared with ciclosporin
      treatment, tacrolimus has been shown to be associated with decreased acute and
      chronic rejection, improved renal function over the long term post-transplant, as
      evidenced by lower serum creatinine concentrations and a slower decline in the
      glomerular filtration rate, and a superior cardiovascular risk profile, as
      demonstrated by lower incidences of hyperlipidaemia and hypertension. The
      incidence of new-onset diabetes in patients receiving tacrolimus is low due to
      continued refinement of tacrolimus-based regimens and a better understanding of
      the effects of tacrolimus on metabolic parameters. Together, these findings may
      translate into improved long-term transplant outcomes with tacrolimus-based
      immunosuppression. In fact, long-term follow-up results from multicentre trials
      plus data from registry analyses are already documenting improved survival with
      this cornerstone immunosuppressant.

PMID- 15575023
TI  - Renal function: defining long-term success.
AB  - One of the leading causes of late graft loss is chronic allograft nephropathy,
      characterized in part by deteriorating renal function. Registry data have
      demonstrated that renal function within the first year post-transplant is an
      important predictor of long-term transplant outcome, with serum creatinine
      concentrations < or =1.5 mg/dl at 6 or 12 months being associated with the
      highest rate of 5 year graft survival. These findings are supported by a
      retrospective, pooled analysis of two multicentre trials in the USA, as well as
      by our own data showing that serum creatinine concentrations may be predictive of
      long-term survival as early as 1 month post-transplant. Analysis of 216 renal
      transplantations carried out at our centre (1996-2000) using immunosuppressive
      therapy based on tacrolimus, corticosteroids and azathioprine (n = 51) or
      mycophenolate mofetil (MMF; n = 70) vs ciclosporin microemulsion, azathioprine
      and corticosteroids (n = 95) showed that the best 3 year graft survival was
      achieved with tacrolimus/MMF therapy. While serum creatinine concentrations at
      this time point were similar for the tacrolimus and ciclosporin treatment groups
      (1.69 and 1.65 mg/dl, respectively), the proportion of patients with functioning
      grafts was significantly higher in the tacrolimus group (84 vs 67%, P = 0.007).
      Similar findings of improved renal function or graft outcomes with tacrolimus- vs
      ciclosporin-based therapy have been reported in other single-centre and
      multicentre trials and a USRDS registry survey. Accumulating data suggest that
      renal function compares well between tacrolimus-based and calcineurin inhibitor
      (CNI)-sparing regimens. Consequently, the vast majority of renal transplant
      recipients maintain good long-term renal function with tacrolimus cornerstone
      immunosuppression without adopting CNI minimization or withdrawal strategies.

PMID- 15575024
TI  - Evaluating mechanisms of post-transplant diabetes mellitus.
AB  - Post-transplant diabetes mellitus (PTDM) is a frequent complication in renal
      transplantation. While both tacrolimus and ciclosporin are known to be associated
      with PTDM, the mechanisms underlying this metabolic disturbance and the relative
      contribution of concomitant corticosteroids have been unclear. At the University
      Hospital Maastricht, a series of studies have been conducted to investigate these
      issues. Administering tacrolimus to non-diabetic, dialysis patients was shown to
      result in a dose-related reduction in insulin secretion without altering insulin
      resistance. The patients who developed diabetes after transplantation already had
      impaired glucose metabolism pre-transplant. In a second study, corticosteroid
      withdrawal from tacrolimus-based immunosuppression reduced insulin resistance
      without changing insulin secretion. Moreover, reducing tacrolimus blood levels by
      30% within the therapeutic window increased both insulin and C-peptide secretion
      by 24 and 36%, respectively. Accordingly, the effects of tacrolimus on insulin
      secretion are both dose dependent and reversible. A comparison of the effects of
      tacrolimus and ciclosporin on glucose metabolism revealed reduced insulin release
      with tacrolimus at week 3 post-transplant, but for the remainder of the 3 year
      follow-up there were no significant differences between the two treatment arms.
      Also, no difference was reported in glucose metabolism following conversion of
      stable renal recipients from ciclosporin to tacrolimus. Therefore, replacing
      tacrolimus with ciclosporin in patients experiencing glucose metabolism
      disturbances is unlikely to be helpful. In a recent study, early corticosteroid
      withdrawal from tacrolimus-based therapy resulted in a significantly lower
      incidence of new-onset diabetes mellitus than that achieved with a corticosteroid
      dose-tapering regimen. In conclusion, corticosteroid minimization plus dose
      optimized tacrolimus immunosuppression is likely to be the best option for
      patients at risk of developing PTDM.

PMID- 15575025
TI  - Pain management by the family physician: the family practice pain education
      project.
AB  - Pain is a common complaint of patients who visit a family physician, and its
      appropriate management is a medical mandate. The fundamental principles for pain
      management are: placing the patient at the center of care; adequately assessing
      and quantifying pain; treating pain adequately; maximizing function; accounting
      for culture and gender differences; identifying red and yellow flags early;
      understanding and differentiating tolerance, dependence and addiction; minimizing
      side effects; and being familiar with and using CAM therapies when good evidence
      of efficacy exists. The pharmacologic management of pain requires thorough
      knowledge of nonsteroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific
      inhibitors, and opioids. A table of equianalgesic dosages is useful because
      patients may need to move from one opioid to another. Accompanying this article
      are papers discussing 5 common pain disorders seen by family physicians,
      including: neck pain, low back pain, joint pain, pelvic pain, and cancer/end of
      life pain. The family physician who learns these principles of pain management
      and the algorithms for these common pain disorders can serve patients well.

PMID- 15575026
TI  - Evaluation and treatment of posterior neck pain in family practice.
AB  - Neck pain is almost universal and is a common patient complaint. Although the
      differential diagnosis is extensive, most symptoms are from biomechanical
      sources, such as axial neck pain, whiplash-associated disorder (WAD), and
      radiculopathy. Most symptoms abate quickly with little intervention. There is
      relatively little high-quality treatment evidence available, and no consensus on
      management of axial neck pain or radiculopathy. A number of general pain
      management guidelines are applicable to neck pain, and specific guidelines are
      available on the management of WAD. The goal of diagnosis is to identify the
      anatomic pain generator(s). Patient history and examination are important in
      distinguishing potential causes and identifying red flags. Diagnostic imaging
      should be ordered only when necessary because of the high incidence of
      asymptomatic radiographic abnormalities. First-line drug treatments include
      acetaminophen, cyclo-oxygenase 2-specific inhibitors, or nonsteroidal anti
      inflammatory drugs. Short-term use of muscle relaxants may be considered. Opioids
      should be used if other treatments are ineffective and continued if improved
      function outweighs impairment. Adjuvant antidepressants and anticonvulsants
      should be considered in chronic or neuropathic pain and coincident depression.
      Epidural steroids should be considered only in radiculopathy. Physical modalities
      supported by evidence should be used. If symptoms have not resolved in 4 to 6
      weeks, re-evaluation and additional workup should be considered.

PMID- 15575027
TI  - Evaluation and treatment of low back pain in family practice.
AB  - Almost all working adults, more than half in any given year, experience low back
      pain. Although the differential diagnosis is extensive, most symptoms have
      biomechanical causes and resolve promptly with little intervention, although
      recurrence is common. History and physical examination are important in
      distinguishing potential causes and identifying "red flags" for more serious
      conditions. Diagnostic imaging should be ordered only when necessary because of
      the high incidence of radiologic abnormalities in asymptomatic persons. Once
      serious illness is ruled unlikely, first-line drug therapy with acetaminophen, a
      cyclo-oxygenase-2 inhibitor or a nonsteroidal anti-inflammatory drug is
      recommended. Short-term use of muscle relaxants may be considered, but they can
      be sedating. Patients should stay as active as possible. Comorbid conditions such
      as sleep disorders, anxiety, or depression should be treated, and psychosocial
      issues should be addressed. Opioids should be prescribed if other treatments have
      been insufficiently effective and if there is evidence of improved function with
      opioid treatment that outweighs adverse effects. Adjuvant antidepressants and
      anticonvulsants should be considered, especially in chronic or neuropathic pain.
      If a structural defect is identified and a diagnostic or therapeutic procedure is
      available, consider referral. If symptoms have not improved within 4 to 6 weeks,
      re-evaluation and additional diagnostic workup should be considered.

PMID- 15575028
TI  - Managing joint pain in primary care.
AB  - Joint pain is a common problem seen by family physicians. Although many pain
      complaints arise from self-limited conditions, a substantial number require
      immediate and ongoing care. Prompt appropriate treatment can help limit symptoms,
      prevent disability, and improve outcomes. The differential diagnosis is varied,
      with both laboratory studies and diagnostic imaging available to help evaluate
      the joint. At the initial evaluation and at each subsequent re-evaluation, there
      should be efforts to identify dangerous conditions and distinguish conditions
      with a disease-specific pathogenesis. Treatment of joint pain consists of both
      pharmacologic and nonpharmacologic modalities. Pharmacologic therapies may
      include medications specific for pain, inflammation, and adjuncts specific to the
      diagnosis. Treatment of pain should proceed in a step-wise fashion providing
      medications appropriate for treating the level of pain. Inflammation is treated
      with physical modalities and nonsteroidal anti-inflammatory or cyclo-oxygenase-2
      inhibitors. Nonpharmacologic therapies may include protection, rest, ice,
      compression, elevation, and simple office procedures. Physical therapy and
      education can assist in the recovery process, and prevent recurrence.

PMID- 15575029
TI  - Management of pelvic pain from dysmenorrhea or endometriosis.
AB  - Many women suffer from pelvic pain, and a great many visit their family doctor
      for diagnosis and treatment. Two common causes are primary dysmenorrhea and
      endometriosis. Primary dysmenorrhea is best treated by prostaglandin inhibition
      from nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2)
      specific inhibitors. Oral contraceptives can be added to improve pain control.
      Endometriosis can be treated with NSAIDs and COX-2-specific inhibitors as well
      but can also be treated with hormonal manipulation or surgery. Empiric treatment
      for endometriosis in selected patients is now accepted, making the disorder
      easier for family physicians to manage.

PMID- 15575030
TI  - Treating adult cancer pain in primary care.
AB  - Family physicians take pride in addressing the totality of a patient's experience
      of disease and are skilled in a multidisciplinary approach to care. As such, they
      have an important role to play in managing adult cancer pain. Although 75% to 90%
      of cancer patients could receive adequate pain relief from routine pharmacologic
      therapies delivered by family physicians, pain continues to be undertreated in
      this population. Pain is a global experience affecting the whole person. Our role
      as patient advocates and educators makes us well suited to participate in the
      current national attempt to redress the lack of attention to this important
      component of suffering. This article reviews commonly seen cancer pain syndromes,
      with specific recommendations concerning assessment, reassessment, management,
      and indications for consultation.

PMID- 15575031
TI  - A bitter pill: formulary variability and the challenge to prescribing physicians.
AB  - BACKGROUND: Multitiered, incentive-based formularies have been increasingly used
      as a mechanism to control prescription drug expenditures. Prescribing physicians
      who manage patients from multiple insurers must be familiar with the variability
      in their patients' formulary incentives to help patients choose therapy wisely.
      However, the degree of formulary variability among and within health plans over
      time is unclear. METHODS: In 6 major health plans in California, we evaluated
      formulary incentive variability in 4 of the 5 drug classes with the highest
      expenditures in California: proton pump inhibitors, hydroxymethylglutaryl
      coenzyme A reductase inhibitors ("statins"), calcium channel blockers, and
      angiotensin-converting enzyme inhibitors. We categorized 20 branded members of
      these classes into either "preferred" or nonpreferred/uncovered categories. We
      calculated the consistency that brands were preferred across health plans and the
      frequency of changes in formulary status for each drug within plans between 2000
      and 2002. RESULTS: None of the branded drugs evaluated were preferred on all
      formularies in 2002, and 10% were not available on any of the formularies.
      Formulary status varied greatly across plans, and more than 60% of drugs were
      preferred on 2 to 4 of the 6 formularies studied. Formulary status within health
      plans varied between 2000 and 2002 in more than half of the plans in the drug
      classes evaluated. CONCLUSIONS: In the drug classes evaluated, over a 2-year
      period, considerable variability was seen among and within formularies over time.
      This variability poses a challenge to physicians who wish to reduce patients'
      expenditures by prescribing the least expensive among similarly effective drugs
      within a drug class. This variability is especially relevant because recent
      legislation increases the likelihood that more Medicare beneficiaries will
      receive their medications from private health plans.

PMID- 15575032
TI  - Rate of breast cancer diagnoses among postmenopausal women with self-reported
      breast symptoms.
AB  - BACKGROUND: Breast cancer rates in women with multiple breast symptoms have not
      been well described. METHODS: We examined the association between self-reported
      symptoms (lump, nipple discharge, pain, other) and breast cancer risk for
      screening and diagnostic mammograms in 57,681 women. Subanalyses evaluated risk
      among women with no prior mammograms, new symptoms, and repeated symptoms. One
      thousand, three hundred and eighty-nine women were diagnosed with cancer within
      12 months of their mammograms. We calculated the breast cancer rate for each
      symptom and odds ratios (OR) with 95% confidence intervals (CI) for breast cancer
      among symptomatic women compared with asymptomatic women. RESULTS: Women
      reporting a lump had an increased odds of breast cancer compared with
      asymptomatic women (OR for diagnostic examination = 2.8, 95% CI = 2.3 to 3.4; OR
      for screening examination = 3.6, 95% CI = 2.6 to 5.0). No other symptoms were
      associated with breast cancer after controlling for a reported lump. A new lump
      at a diagnostic examination was significantly predictive of cancer among women
      with no prior mammograms (OR = 12.2, 95% CI = 2.8 to 53.5); reporting symptoms at
      2 successive exams had little effect on breast cancer risk (OR for lump = 1.2,
      95% CI = 0.6 to 2.5). CONCLUSIONS: Having a lump is the most predictive symptom
      of breast cancer whether it is reported at a screening or diagnostic examination
      or in conjunction with other symptoms.

PMID- 15575033
TI  - Overcoming obstacles to skin cancer examinations and prevention counseling for
      high-risk patients: results of a national survey of primary care physicians.
AB  - OBJECTIVE: Primary care physicians are in a unique position to perform skin
      cancer examinations and provide prevention counseling, given that approximately
      40% of office visits to physicians in the United States are to a family
      practitioner or internist. Compared with family or self-detection, physician
      detection is associated with an increased probability of detecting thinner
      melanomas. However, little research has attempted to identify the major obstacles
      to performing a skin cancer examination and recommending prevention practices.
      METHODS: In the spring of 2002, we surveyed primary care physicians from all 50
      states, including family medicine physicians, internists, and general
      practitioners sampled from the American Medical Association's Medical Marketing
      Services' database. There were 4 primary outcome variables related to early
      detection and prevention practices for average-risk patients and patients with
      risk factors: performing a full-body skin examination; recommending regular skin
      self-examination; and recommending sun protection practices and avoidance of
      tanning booths for patients younger than age 35. RESULTS: We received surveys
      from 380 (60%) of 632 eligible physicians. Nearly 60% of physicians routinely
      performed full-body examinations with their high-risk patients. In the regression
      analysis of factors influencing physician examination of high-risk patients, lack
      of time was the strongest barrier [odds ratio (OR) 0.3 (95% confidence interval
      (CI) 0.2 to 0.6)]. Physicians using the most information sources [OR 2.5 (95% CI
      1.3 to 4.8)] were the most likely to examine their high-risk patients. Physicians
      whose patients requested a skin examination were more likely to examine their
      patients compared with physicians whose patients did not request such an
      examination (P < .01). CONCLUSIONS: Concerted public and professional education
      efforts must be made to provide resources that help physicians efficiently weave
      skin cancer examinations and prevention counseling into routine practice while
      also motivating high-risk patients to request full-body examinations and
      counseling.

PMID- 15575034
TI  - Addressing cardiovascular disease in women: focus on dyslipidemia.
AB  - BACKGROUND: There is a need to better diagnose and treat women who may be at risk
      for cardiovascular disease. This is emphasized by the impending release of
      evidence-based guidelines for the prevention of cardiovascular disease in women.
      Dyslipidemia is one of the most important modifiable risk factors for coronary
      heart disease (CHD) and is the focus of the current literature review. METHODS:
      Medical literature on treating cardiovascular disease and cholesterol disorders
      in women was reviewed by searching Medline, including a selective search for
      randomized controlled clinical trials of lipid therapy. In addition, current
      dyslipidemia treatment guidelines were reviewed. RESULTS AND CONCLUSIONS:
      Subgroup analyses of both primary and secondary prevention trials have shown that
      lipid-modifying drugs offer benefits to women comparable with those seen in men.
      Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid
      modifying therapy for the reduction of coronary risk. However, there are
      differences between the sexes in the lipid profile that may have clinical
      implications. In women, changes in high-density lipoprotein cholesterol (HDL-C)
      and triglyceride levels are better predictors of coronary risk than LDL-C or
      total cholesterol. Thus, treatment beyond LDL-C may be of greater importance in
      women than in men. Furthermore, treatment options that provide improvement in all
      aspects of the lipid profile should be considered.

PMID- 15575035
TI  - Office-based ultrathin esophagogastroduodenoscopy in a primary care setting.
AB  - BACKGROUND: Upper gastrointestinal complaints are common in primary care. These
      patients are often referred for evaluation with the use of
      esophagogastroduodenoscopy. This study examines the feasibility and safety of
      office-based ultrathin (diameter, 5.9 mm) esophagogastroduodenoscopy (u-EGD)
      without conscious sedation in a primary care setting. METHODS: This study is a
      retrospective chart review in a university-based family medicine residency in the
      southeastern United States. Charts were reviewed for adult outpatients (N = 126)
      who were referred for further evaluation of heartburn, dyspepsia, or epigastric
      pain and who elected to undergo u-EGD procedure. We examined the number of
      patients willing to undergo office-based u-EGD, patient demographics, procedure
      indications and findings, patient request for oral benzodiazepines, and procedure
      and recovery times. RESULTS: Of the 132 patients asked to participate in office
      based u-EGD, 126 (95.4%) were willing to undergo this procedure (mean age, 47.6
      +/- 1.3; 75% women). Of 126 patients, 122 (96.8%) tolerated office-based u-EGD,
      and 80.6% of patients requested oral anxiolytic medications. Significantly more
      women than men requested oral anxiolytic medications (84.0% versus 65.6%,
      respectively; P = .026). The retroflexion maneuver was completed in 120 of 122
      (98.4%) patients, and the second portion of duodenum was reached in 122 of 122
      (100%) patients. Mean procedure time was 16.9 +/- 0.7 minutes, and mean recovery
      time was 3.8 +/- 0.2 minutes. There were no complications reported in this case
      series. CONCLUSIONS: The majority of patients can tolerate office-based u-EGD
      without conscious sedation in a primary care setting, but most patients request
      oral anxiolytic medications. Statistically more women request oral anxiolytic
      medications than do men.

PMID- 15575036
TI  - Primary care experience and racial disparities in self-reported health status.
AB  - CONTEXT: Access to high quality primary care was identified by Healthy People
      2010 as one of the mechanisms through which racial and ethnic disparities in
      health might be reduced. Despite the well-established connections between good
      primary care and health, the scientific evidence on whether good primary care can
      reduce racial disparities in health is sparse. OBJECTIVE: To examine whether
      better primary care experience can attenuate racial and ethnic disparities in
      self-reported health status. DATA SOURCES: The 1996 to 1997 and 1998 to 1999 data
      from the Community Tracking Study (CTS) sponsored by the Robert Wood Johnson
      Foundation. STUDY DESIGN: Cross-sectional, bivariate, and multivariate analyses
      of inter-relationships between self-rated general and mental health status,
      access to and interpersonal relationship with primary care provider, and
      vulnerability measured by race and poverty status. RESULTS: We found that higher
      quality primary care levels are associated with reduced racial and ethnic
      disparities in health status, as measured by self-rated general and mental
      health. This relationship is particularly pronounced for the racial and ethnic
      minorities living at or below poverty level. Based on the data from 1996 to 1999,
      the study also confirmed the presence of significant and persistent health
      differences across racial and ethnic groups. CONCLUSION: Promoting primary care
      may be a viable approach toward reducing racial and ethnic disparities in self
      reported health status.

PMID- 15575037
TI  - When do older patients change primary care physicians?
AB  - BACKGROUND: Concerns have been raised about changes in the health care system
      that may disrupt continuity of care and thereby reduce the quality of that care.
      The purpose of this study was to look at the reasons that older patients give for
      changing primary care physicians (PCPs) and to look at relationships between the
      duration of the PCP-patient relationship and the perceived quality of primary
      care received. METHODS: We analyzed data collected during the first 2 years of a
      longitudinal study of primary care patients 65 years of age and older. Variables
      included sociodemographic characteristics, duration of relationship with current
      PCP, reasons for leaving last PCP, estimated numbers of visits to PCP, other
      clinics, and emergency departments, and admissions to hospitals and nursing homes
      in the last year, self-rated health, 2 measures of health-related quality of
      life, and the Components of Primary Care Index (CPCI). RESULTS: 799 patients of
      23 PCPs were enrolled in year 1 of the longitudinal study, and 579 were re
      evaluated in year 2. The mean and median PCP-patient relationship durations were
      10.27 and 8 years, respectively. Duration of the PCP-patient relationship was
      associated with greater patient age, income, level of education, and frequency of
      visits to the PCP. Longer relationship duration was also associated with higher
      scores on all 8 CPCI subscales. The distribution of reasons for changing PCP was
      associated with duration of relationship; those with a longer relationship were
      more likely to change involuntarily. Insurance-related reasons for changing PCP
      were more common in those who had changed more recently. One hundred and fourteen
      (14%) changed PCP during the first year of the study. Three CPCI subscale scores
      predicted PCP change, accumulated knowledge, communication, and family
      orientation. Eighty-seven percent changed involuntarily, 44% for insurance
      related reasons and 40% because their doctors had moved, retired, or died.
      CONCLUSIONS: Older patients, particularly those who are older and have more
      education and income, tend to stay with their PCPs until they are forced to
      change. The longer they stay in the relationship, the better they feel about the
      quality of the primary services they receive. Changes in the health care system
      may have increased the number of patients forced to change PCP.

PMID- 15575038
TI  - A primer of the HIPAA Privacy Rule for practice-based researchers.

PMID- 15575039
TI  - Human metapneumovirus: a newly described respiratory tract pathogen.
AB  - Human metapneumovirus is an emerging human respiratory pathogen first discovered
      in 2001. It clinically resembles respiratory syncytial virus, can cause both
      upper and lower tract disease, and has been associated with serious illness in
      the young, among the immunosuppressed, and in the chronically ill. Cough and
      congestion are frequently reported, and respiratory failure may occur. Initial
      infection occurs during early childhood, and repeated infections throughout life
      impart only transient immunity. Diagnosis is by reverse transcription-polymerase
      chain reaction or rising serologic titers. No commercial laboratory tests or
      treatments are available. Primary care physicians should maintain vigilance for
      outbreaks of newly discovered and emerging respiratory illnesses.

PMID- 15575040
TI  - Cerebrospinal fluid neutrophilic pleocytosis in hospitalized West Nile virus
      patients.
AB  - A description of 7 consecutive patients admitted for various forms of
      neurological impairment. All these patients were found to have cerebrospinal
      fluid positive for West Nile virus IgM, and routine bacterial cultures were
      negative. Six of these patients did not present with the typical lymphocytic
      pleocytosis often quoted when discussing a viral meningitis/encephalitis; rather
      most presented with a cerebrospinal fluid neutrophilia.

PMID- 15575041
TI  - Numeracy and medicine: key family physician attitudes about communicating
      probability with patients.

PMID- 15575042
TI  - The impact of clinical practice guidelines should not be overestimated.

PMID- 15575043
TI  - Challenges for family medicine and for family physicians.

PMID- 15575047
TI  - Images in clinical medicine. The tale of Phineas Gage, digitally remastered.

PMID- 15575048
TI  - Avian influenza--a challenge to global health care structures.

PMID- 15575049
TI  - Rationing influenza vaccine.

PMID- 15575050
TI  - Running like water--the omnipresence of hepatitis E.

PMID- 15575051
TI  - America's Gulag Archipelago.

PMID- 15575052
TI  - Disruption of C/EBPalpha function in acute myeloid leukemia.

PMID- 15575053
TI  - Catheter ablation for atrial fibrillation in congestive heart failure.
AB  - BACKGROUND: Congestive heart failure and atrial fibrillation often coexist, and
      each adversely affects the other with respect to management and prognosis. We
      prospectively evaluated the effect of catheter ablation for atrial fibrillation
      on left ventricular function in patients with heart failure. METHODS: We studied
      58 consecutive patients with congestive heart failure and a left ventricular
      ejection fraction of less than 45 percent who were undergoing catheter ablation
      for atrial fibrillation. We selected as controls 58 patients without congestive
      heart failure who were undergoing ablation for atrial fibrillation, matched
      according to age, sex, and classification of atrial fibrillation. We evaluated
      the patients' left ventricular function and dimensions, symptom score, exercise
      capacity, and quality of life at baseline and at months 1, 3, 6, and 12. RESULTS:
      After a mean (+/-SD) of 12+/-7 months, 78 percent of the patients with congestive
      heart failure and 84 percent of the controls remained in sinus rhythm (P=0.34)
      (69 percent and 71 percent, respectively, were in sinus rhythm without the
      administration of antiarrhythmic drugs). The patients with congestive heart
      failure had significant improvement in left ventricular function (increases in
      the ejection fraction and fractional shortening of 21+/-13 percent and 11+/-7
      percent, respectively; P<0.001 for both comparisons), left ventricular dimensions
      (decreases in the diastolic and systolic diameters of 6+/-6 mm and 8+/-7 mm,
      respectively; P=0.03 and P<0.001, respectively), exercise capacity, symptoms, and
      quality of life. The ejection fraction improved significantly not only in
      patients without concurrent structural heart disease (24+/-10 percent, P<0.001)
      and those with inadequate rate control before ablation (23+/-10 percent,
      P<0.001), but also in those with coexisting heart disease (16+/-14 percent,
      P<0.001) and adequate rate control before ablation (17+/-15 percent, P<0.001).
      CONCLUSIONS: Restoration and maintenance of sinus rhythm by catheter ablation
      without the use of drugs in patients with congestive heart failure and atrial
      fibrillation significantly improve cardiac function, symptoms, exercise capacity,
      and quality of life.

PMID- 15575054
TI  - Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the
      pocket" approach.
AB  - BACKGROUND: In-hospital administration of flecainide and propafenone in a single
      oral loading dose has been shown to be effective and superior to placebo in
      terminating atrial fibrillation. We evaluated the feasibility and the safety of
      self-administered oral loading of flecainide and propafenone in terminating
      atrial fibrillation of recent onset outside the hospital. METHODS: We
      administered either flecainide or propafenone orally to restore sinus rhythm in
      268 patients with mild heart disease or none who came to the emergency room with
      atrial fibrillation of recent onset that was hemodynamically well tolerated. Of
      these patients, 58 (22 percent) were excluded from the study because of treatment
      failure or side effects. Out-of-hospital self-administration of flecainide or
      propafenone--the "pill-in-the-pocket" approach--after the onset of heart
      palpitations was evaluated in the remaining 210 patients (mean age [+/-SD], 59+/
      11 years). RESULTS: During a mean follow-up of 15+/-5 months, 165 patients (79
      percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92
      percent) were treated 36+/-93 minutes after the onset of symptoms. Treatment was
      successful in 534 episodes (94 percent); the time to resolution of symptoms was
      113+/-84 minutes. Among the 165 patients with recurrences, the drug was effective
      during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects
      were reported during one or more arrhythmic episodes by 12 patients (7 percent),
      including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac
      side effects in 11 patients. The numbers of monthly visits to the emergency room
      and hospitalizations were significantly lower during follow-up than during the
      year before the target episode (P<0.001 for both comparisons). CONCLUSIONS: In a
      selected, risk-stratified population of patients with recurrent atrial
      fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate
      of compliance by patients, a low rate of adverse events, and a marked reduction
      in emergency room visits and hospital admissions.

PMID- 15575055
TI  - Elective single-embryo transfer versus double-embryo transfer in in vitro
      fertilization.
AB  - BACKGROUND: The risks of premature birth and perinatal death are increased after
      in vitro fertilization. These risks are mainly due to the high incidence of
      multiple births, which relates to the number of embryos transferred. METHODS: We
      performed a randomized, multicenter trial to assess the equivalence of two
      approaches to in vitro fertilization with respect to the rates of pregnancy that
      result in at least one live birth and to compare associated rates of multiple
      gestation. Women less than 36 years of age who had at least two good-quality
      embryos were randomly assigned either to undergo transfer of a single fresh
      embryo and, if there was no live birth, subsequent transfer of a single frozen
      and-thawed embryo, or to undergo a single transfer of two fresh embryos.
      Equivalence was defined as a difference of no more than 10 percentage points in
      the rates of pregnancy resulting in at least one live birth. RESULTS: Pregnancy
      resulting in at least one live birth occurred in 142 of 331 women (42.9 percent)
      in the double-embryo-transfer group as compared with 128 of 330 women (38.8
      percent) in the single-embryo-transfer group (difference, 4.1 percentage points;
      95 percent confidence interval, -3.4 to 11.6 percentage points); rates of
      multiple births were 33.1 percent and 0.8 percent, respectively (P<0.001). These
      results do not demonstrate equivalence of the two approaches in rates of live
      births, but they do indicate that any reduction in the rate of live births with
      the transfer of single embryos is unlikely to exceed 11.6 percentage points.
      CONCLUSIONS: In women under 36 years of age, transferring one fresh embryo and
      then, if needed, one frozen-and-thawed embryo dramatically reduces the rate of
      multiple births while achieving a rate of live births that is not substantially
      lower than the rate that is achievable with a double-embryo transfer.

PMID- 15575056
TI  - Mutation of CEBPA in familial acute myeloid leukemia.
AB  - We describe a family in whom three members affected by acute myeloid leukemia
      (AML) had an identical, 212delC mutation in CEBPA, the gene encoding the
      granulocytic differentiation factor C/EBPalpha. Unaffected family members did not
      have this mutation. Latent periods of 10, 18, and 30 years elapsed before the
      onset of overt leukemia in the three patients. One of them had a second CEBPA
      mutation, but only at the time of diagnosis. All three patients are currently
      well, with no abnormalities in the bone marrow. CEBPA mutation is apparently the
      primary event in the development of AML in this family.

PMID- 15575057
TI  - Clinical practice. Newly diagnosed atrial fibrillation.

PMID- 15575058
TI  - Contagious acute gastrointestinal infections.

PMID- 15575059
TI  - Images in clinical medicine. Benign hepatic cyst.

PMID- 15575060
TI  - Clinical problem-solving. Why "why" matters.

PMID- 15575061
TI  - Medical research and the news media.

PMID- 15575062
TI  - Atrial fibrillation and heart failure--five more years.

PMID- 15575063
TI  - Elective single-embryo transfer--has its time arrived?

PMID- 15575064
TI  - The fragility of the U.S. vaccine supply.

PMID- 15575065
TI  - Hyperkalemia after the publication of RALES.

PMID- 15575066
TI  - Hyperkalemia and inhibitors of the renin-angiotensin-aldosterone system.

PMID- 15575067
TI  - Venous thrombosis in children.

PMID- 15575068
TI  - Circulating epithelial cells in breast cancer.

PMID- 15575069
TI  - Bipolar disorder.

PMID- 15575070
TI  - Case 24-2004: recurrent gastrointestinal bleeding in a 48-year-old man.

PMID- 15575071
TI  - Follow-up 26 years after treatment for acute myelogenous leukemia.

PMID- 15575072
TI  - [Nobel Prize for Medicine 2004. Olfaction: "lower sense" achieves high
      significance].

PMID- 15575073
TI  - [Corneal changes in Lowe syndrome].

PMID- 15575074
TI  - Ultrasound measurement of the volume of musculus quadriceps after knee joint
      injury.
AB  - The monitoring of the recovery of femoral muscles, after the knee-joint injury,
      is possible by the method of ultrasound measurement of the muscular volume. In a
      clearly defined longitudinal study, our object was to standardize the method of
      ultrasound measurement of muscular volume and to evaluate its adequacy in
      practical application in quadriceps muscle rehabilitation. The ultrasound
      measurements of m. rectus femoris and m. vastus intermedius were conducted in
      three intervals: in the first 24 hours after the injury; after 1 week, when
      immobilization was removed; and after 6 weeks, when rehabilitation was finished.
      The study comprised 30 patients with knee-joint injury, and 30 asymptomatic
      subjects, who formed the control group. The results showed significant decrease
      of muscular volume (mm3) after joint immobilization on injured leg and a
      significant increase of volume after rehabilitation. The same differences were
      observed on healthy legs, but without significance. Within the same intervals,
      there were no changes in the muscular mass in the control group. M. rectus
      femoris was completely recovered in greater number of patients (54.1%), comparing
      to m. vastus intermedius (25.4%). We conclude that the ultrasound is an
      appropriate method for monitoring the process of muscular atrophy during
      immobilization, as well as the course of muscular restitution during the physical
      therapy.

PMID- 15575075
TI  - Infectivity studies of both ash and air emissions from simulated incineration of
      scrapie-contaminated tissues.
AB  - We investigated the effectiveness of 15 min exposures to 600 and 1000 degrees C
      in continuous flow normal and starved-air incineration-like conditions to
      inactivate samples of pooled brain macerates from hamsters infected with the 263K
      strain of hamster-adapted scrapie with an infectivity titer in excess of 10(9)
      mean lethal doses (LD50) per g. Bioassays of the ash, outflow tubing residues,
      and vented emissions from heating 1 g of tissue samples yielded a total of two
      transmissions among 21 inoculated animals from the ash of a single specimen
      burned in normal air at 600 degrees C. No other ash, residue, or emission from
      samples heated at either 600 or 1000 degrees C, under either normal or starved
      air conditions, transmitted disease. We conclude that at temperatures approaching
      1000 degrees C under the air conditions and combustion times used in these
      experiments, contaminated tissues can be completely inactivated, with no release
      of infectivity into the environment from emissions. The extent to which this
      result can be realized in actual incinerators and other combustion devices will
      depend on equipment design and operating conditions during the heating process.

PMID- 15575076
TI  - CMS issues new OASIS guidance for accurate coding of pressure ulcers.

PMID- 15575077
TI  - Proceedings of the 4th International Conference on Innovations and Challenges in
      Prostate Cancer: Prevention, Detection and Treatment. November 7-8, 2003,
      Cambridge, Massachusetts, USA.

PMID- 15575078
TI  - Rasmussen's encephalitis.
AB  - Rasmussen's encephalitis, a syndrome characteristically present-ing in children
      with the onset of partial motor seizures followed by progressive hemiparesis and
      cognitive impairment, and accompanied by unilateral cerebral atrophy, was
      described nearly 50 years ago, yet the cause and optimum treatment remain
      unclear. Although it was originally presumed to have a viral aetiology, the
      possible roles of antibody-mediated mechanisms and more recently cell-mediated
      immunity in its pathogenesis have come under increasing scrutiny in the last ten
      years. These developments are discussed, together with a review of the clinical
      features. The advances in treatment which have accompanied these changes are also
      assessed.

PMID- 15575079
TI  - [Immunopharmacological approach in elucidating the mechanism responsible for
      allergic inflammation].

PMID- 15575080
TI  - [Emerging and re-emerging infections--HIV infection/AIDS].

PMID- 15575081
TI  - Expression and significances of Id1 helix-loop-helix protein overexpression in
      gastric cancer.
AB  - The Id family of helix-loop-helix proteins is involved in a variety of biological
      processes, including development,proliferation, and angiogenesis. There is
      emerging evidence for deregulation of Id proteins in some cancers. Hence we
      determined Id expression in gastric cancer. To elucidate the involvement of Idl
      in gastric carcinogenesis, Immunohistochemistry was carried out on paraffin
      embedded gastric cancer sections. By analyzing the relationship between the Idl
      staining index of individual tumors and the patient's clinical parameters,
      including histological grade, clinical stage, and presence of metastases, we
      found that strong Idl expression was associated with poorer differentiation and
      more aggressive behavior of tumor cells. To further explore Idl expression in
      human gastric carcinomas, Western blot analysis was performed to analyze Idl
      protein expression in 15 pairs of gastric tissues and cancers and in gastric cell
      lines. Idl was found to be expressed at higher levels in 11/15 cancer tissues
      compared to adjacent tissues. Idl was upregulated more prominently in the poorly
      differentiated cell lines than in the well-differentiated ones. Semiquantitative
      RT-PCR was carried out to investigate the expression of mRNA of Idl in gastric
      cancer cell lines and it was upregulated in most of them. Our results demonstrate
      that Idl protein may play an important role in the process of gastric
      carcinogenesis and high-level Id I expression may be related to the malignant
      potential of tumor cells.

PMID- 15575082
TI  - New Therapies and Diagnostic Techniques for Respiratory Disease. Abstracts of a
      meeting. October 12-15, 2003, Santa Fe, New Mexico, USA.

PMID- 15575083
TI  - Abstracts of the 42nd Annual Meeting of the Academy of Aphasia. October 17-19,
      2004, Chicago, Illinois, USA.

PMID- 15575084
TI  - [Abstracts of the 67th National Congress of the Italian Society of Occupational
      Medicine and Industrial Health (SIMLII)and the 75th anniversary of the founding
      of the Italian Society of Occupational Medicine. Sorrento, Italy, 3-6 November
      2004].

PMID- 15575085
TI  - [Abstracts of the 3rd National Congress of the Italian Society of Pathology and
      Cytodiagnosis, Italian division of the International Academy of Pathology (SIAPEC
      IAP).26-30 September 2004, Florence, Italy].

PMID- 15575086
TI  - Abstracts of the 29th Annual Meeting of the Irish Endocrine Society . Dublin, 5-6
      November 2004.

PMID- 15575087
TI  - Abstracts of the 31st Annual Meeting of the Japanese Society of Toxicology. July
      6-8, 2004, Osaka, Japan.

PMID- 15575089
TI  - Contracts keep drug research out of reach.

PMID- 15575088
TI  - Abstracts of the 8th World Congress of Cardiac Rehabilitation and Secondary
      Prevention. Dublin, Ireland, May 23-26, 2004.

PMID- 15575090
TI  - Abstracts of the 23rd Conference of the European Society for Microcirculation.
      Lisbon, Portugal, September 8-11, 2004.

PMID- 15575091
TI  - [Abstracts of the Bavarian Ophthalmology Association meeting. 16-17 October 2004,
      Erlangen, Germany].

PMID- 15575092
TI  - [Annual Conference of the Serbian Physiological Society. Zrenjanin, 7-9 November
      2003. Risk factors in health: from molecules to a scientific basis for
      prevention].

PMID- 15575095
TI  - [Re: Koneczny et al. Klinische Padiatrie, Issue 4, July/August 2004, Volume
      216:215-234].

PMID- 15575096
TI  - Walking the talk of trust in human subjects research: the challenge of regulating
      financial conflicts of interest.

PMID- 15575097
TI  - Research, regulations, and responsibility: confronting the compliance myth--a
      reaction to Professor Gatter.

PMID- 15575098
TI  - Preventing violence and related health-risking social behaviors in adolescents.

PMID- 15575099
TI  - Can't lift a finger. Schwarzenegger vetoes 'lift team' bill that would save RNs'
      backs.

PMID- 15575100
TI  - Health care reform in motion. Canadian RNs see promise despite problems.

PMID- 15575101
TI  - 'Liberation' in the Heartland. Chicago RNs turn to CNA and NNOC for effective
      representation.

PMID- 15575102
TI  - Pricing & profits. High hospital charges linked to high hospital profits.

PMID- 15575104
TI  - Will authors pay to publish?

PMID- 15575105
TI  - KTP photoselective laser vaporization of the prostate: indications, procedure,
      and nursing implications.
AB  - Over the past decade, there has been a concerted effort to surgically relieve the
      bladder outlet obstructive symptoms in men with benign prostatic hypertrophy
      (BPH) by using a laser. Recent improvements in laser technology have led to the
      development of promising new treatment modalities. The potassium-titanyl
      phosphate photoselective laser vaporization of the prostate procedure effectively
      vaporizes the obstructing prostatic adenoma in a 1-day surgery procedure. Current
      results show that this procedure provides a feasible option for men seeking long
      term relief of bladder outlet obstructive symptoms due to BPH.

PMID- 15575106
TI  - Postoperative management and rehabilitation of patients receiving an ileal
      orthotopic bladder substitution.
AB  - Ileal orthotopic bladder substitution has become one of the main therapeutic
      options following radical cystectomy for invasive bladder cancer. While careful
      patient selection and the surgical technique are necessary to obtain good long
      term results and a satisfactory quality of life, postoperative management is also
      of utmost importance. It includes successful voiding rehabilitation (micturition
      technique, complete bladder emptying, increase of functional reservoir capacity,
      and sphincter training) and a meticulous lifelong followup.

PMID- 15575107
TI  - Urodynamics: the incidence of urinary tract infection and autonomic dysreflexia
      in a challenging population.
AB  - Individuals with spinal cord injury and other neurologic disorders have
      conditions that affect their urologic systems and their ability to store and
      empty urine. Urodynamic tests evaluate this dysfunction, but they have added
      risks of urinary tract infections and autonomic dysreflexia. A descriptive study
      investigated the incidence of urinary tract infections and autonomic dysreflexia
      in a large neurogenic population receiving urodynamics using standardized
      protocols.

PMID- 15575108
TI  - Transrectal ultrasound prostate biopsy (TRUS-Bx): patient perspectives.
AB  - Prostate cancer continues to be a complex disease for which a cause or cure has
      not yet been identified. Many men are diagnosed each year and the incidence is
      likely to increase as greater numbers of men reach "old" age. The transrectal
      ultrasound prostate biopsy (TRUS-Bx) is the predominant method to diagnose
      prostate cancer, and varying levels of patient pain have been associated with the
      procedure. The purpose of this ethnographic research study was to describe TRUS
      Bx from the patients' perspective. Results from this study indicated that TRUS-Bx
      pain was strongly influenced by psychosocial factors, as well as physical aspects
      of the procedure.

PMID- 15575109
TI  - Evaluation of a patient education tool to reduce the incidence of incontinence
      post-prostate surgery.
AB  - A pelvic floor muscle exercise program can reduce the incidence of incontinence
      post-prostate surgery. The purpose of this study was to validate a new education
      tool, a refrigerator magnet, in comparison to a paper copy with the same
      information, to determine if patient compliance with the exercises increased.

PMID- 15575110
TI  - Choosing among qualitative traditions.

PMID- 15575111
TI  - Getting ready for certification: urinary tract inflammation and diseases.

PMID- 15575112
TI  - Update on bioterrorism preparedness.
AB  - Knowledge and preparation are the best defense against a biological attack. By
      understanding the epidemiology of biological warfare agents and diseases,
      strategies can be planned to decrease the morbidity and mortality associated with
      them. There is an urgent need for developing rapid diagnostic tests, effective
      vaccines, and drug therapy to defend against biological weapon attacks. The CDC,
      along with other agencies and partners, are defining how the public health system
      is to prepare for and respond to public health threats posed by terrorism.

PMID- 15575114
TI  - Resolving the nursing shortage: caring for yourself.

PMID- 15575116
TI  - Fad diets and obesity--Part III: a rapid review of some of the more popular low
      carbohydrate diets.
AB  - Low-carbohydrate books continue to be some of the biggest selling publications in
      the United States. However, what are the similarities and differences between
      some of the most popular books? This overview of what some of these books
      advocate or discourage is important to better facilitate the discussion between
      the health professional and the patient interested in some of these methods.
      Regardless of the low-carbohydrate diet discussed with patients and whether or
      not health professionals agree or disagree with this approach, it is imperative
      that health professionals at least learn the basics of some of the more popular
      diets to facilitate better communication between the practitioner and patient.

PMID- 15575117
TI  - Good grief: moving from grief to comic relief.

PMID- 15575118
TI  - Aging and community care.

PMID- 15575119
TI  - Community care in Europe. The Aged in Home Care project (AdHOC).
AB  - BACKGROUND AND AIMS: Community care for older people is increasing dramatically
      in most European countries as the preferred option to hospital and long-term
      care. While there has been a rapid expansion in Evidence-Based Medicine, apart
      from studies of specific interventions such as home visiting and hospital at home
      (specialist visits or hospital services provided to people in their own homes in
      the community), there is little evidence of characteristics of the recipients of
      community care services or the organisation of services that produce the best
      outcomes for them and their informal carers. The AdHOC Study was designed to
      compare outcomes of different models of community care using a structured
      comparison of services and a comprehensive standardised assessment instrument
      across 11 European countries. This paper describes the study and baseline data.
      METHODS: 4,500 people 65 years and older already receiving home care services
      within the urban areas selected in each country were randomly sampled. They were
      assessed with the MDS-HC (Minimum Data Set-Home Care) instrument, containing over
      300 items, including socio-demographic, physical and cognitive characteristics of
      patients as well as medical diagnoses and medications received. These data were
      linked to information on the setting, services structures and services
      utilization, including use of hospital and long-term care. After baseline
      assessment, patients were re-evaluated at 6 months with an abbreviated version of
      the instrument, and then at the end of one year. Data collection was performed by
      specially-trained personnel. In this paper, socio-demographics, physical and
      cognitive function and provision of hours of formal care are compared between
      countries at baseline. RESULTS: The final study sample comprised 3,785 patients;
      mean age was 82+/-7.2 years, 74.2% were females. Marital and living status
      reflected close family relationships in southern Europe relative to Nordic
      countries, where 5 times as many patients live alone. Recipients of community
      care in France and Italy are characterised by very high physical and cognitive
      impairment compared with those in northern Europe, who have comparatively little
      impairment in Activities of Daily Living and cognitive function. The provision of
      formal care to people with similar dependency varies extremely widely with very
      little formal care in Italy and more than double the average across all levels of
      dependency in the UK. CONCLUSIONS: The AdHOC study, by virtue of the use of a
      common comprehensive standardised assessment instrument, is a unique tool in
      examining older recipients of community care services in European countries and
      their widely varied organisation. The extreme differences seen in dependency and
      hours of care illustrate the probable contribution the study will make to
      developing an evidence based on the structure, quantity and targeting of
      community care, which will have major policy implications.

PMID- 15575120
TI  - Drugs and falls in older people in geriatric care settings.
AB  - BACKGROUND AND AIMS: Falls and their consequences constitute serious health
      problems in the older population. The aim was to study predisposing factors for
      falls among older people in geriatric care settings, focusing on drugs. METHODS:
      This population-based study, with a cross-sectional design, analysed all
      geriatric care settings, comprising 68 residential care facilities, 31 nursing
      homes, 66 group dwellings for people with dementia, seven rehabilitation/short
      stay units, two somatic geriatric and two psychogeriatric clinics, in the county
      of Vasterbotten; 3604 residents with a mean age of 83.3+/-7.0 (65-103) years (68%
      women) were included. The residents were assessed by means of the Multi
      Dimensional Dementia Assessment Scale (MDDAS) that measures, for example,
      mobility, paresis, vision, hearing, functions of activities of daily living
      (ADL), and behavioural and psychiatric symptoms. Drug consumption and falls
      during the previous week were recorded. RESULTS: Three hundred and one residents
      (8.4%) had sustained a fall at least once during the preceding week. Multivariate
      analyses showed that a history of falls, the ability to get up from a chair, the
      need for a helper when walking, pain, cognitive impairment, and use of
      neuroleptics or antidepressants were all associated with being a faller. Among
      the antidepressants, selective serotonin reuptake inhibitors (SSRIs) but not
      serotonin and noradrenalin reuptake inhibitors (SNRIs) were associated with
      falls. Cholinesterase inhibitors were not associated with falls. CONCLUSIONS:
      Like functional and cognitive impairment, treatments with antidepressants and
      neuroleptics are predisposing factors for falls in older people in residential
      care. However, there seem to be differences between subgroups among these drugs
      and, from the perspective of fall prevention, SNRIs rather than SSRIs should
      perhaps be preferred in the treatment of depression in older people.

PMID- 15575121
TI  - Not less but different: psychotropic drug utilization trends in Norwegian nursing
      homes during a 12-year period. The Bergen District Nursing Home (BEDNURS) Study.
AB  - BACKGROUND AND AIMS: The use of psychotropic drugs in nursing homes is generally
      considered to be inappropriately high. The aim of the present survey was to
      compare psychotropic drug use in nursing homes (NHs) in 1985 relative to 1996/97,
      and to explore predictors for this drug use. METHODS: Cross-sectional study.
      Mental capacity was assessed by means of the Clinical Dementia Rating scale
      (CDR), and behavior registered by trained nurses. Scheduled, daily use of
      psychotropic drugs among long-term care residents in 1985 (N=1247) and 1996/97
      (N=1035) was recorded. Bivariate analyses and logistic regression analyses were
      applied to establish predictors for psychoactive drug use. RESULTS: From 1985 to
      1996/97, the proportion of residents using any psychotropic drug increased from
      52 to 57%. Antipsychotic drug use decreased from 33 to 22%, while anxiolytics
      increased from 11 to 16%, hypnotics from 11 to 14%, and antidepressants from 12
      to 31%. Psychotropic drug use was predominantly associated with behavioral
      symptoms and not with mental impairment. Concurrent use of two or more
      psychotropic drugs increased from 23 to 32% of all psychotropic users.
      CONCLUSIONS: During the study period, a substantial decline in the use of
      antipsychotics was observed, but a generally increased overall use of
      psychotropic drugs, particularly antidepressants. Psychotropic drug treatment was
      mainly associated with behavioral symptoms.

PMID- 15575122
TI  - Effects of a fall prevention program including exercise on mobility and falls in
      frail older people living in residential care facilities.
AB  - BACKGROUND AND AIMS: Impaired mobility is one of the strongest predictors for
      falls in older people. We hypothesized that exercise as part of a fall prevention
      program would have positive effects, both short- and long-term, on gait, balance
      and strength in older people at high risk of falling and with varying levels of
      cognition, residing in residential care facilities. A secondary hypothesis was
      that these effects would be associated with a reduced risk of falling. METHODS:
      187 out of all residents living in 9 facilities, > or =65 years of age were at
      high risk of falling. The facilities were cluster-randomized to fall intervention
      or usual care. The intervention program comprised: education, environment,
      individually designed exercise, drug review, post-fall assessments, aids, and hip
      protectors. Data were adjusted for baseline performance and clustering. RESULTS:
      At 11 weeks, positive intervention effects were found on independent ambulation
      (FAC, p=0.026), maximum gait speed (p=0.002), and step height (> or =10 cm,
      p<0.001), but not significantly on the Berg Balance Scale. At 9 months (long-term
      outcome), 3 intervention and 15 control residents had lost the ability to walk
      (p=0.001). Independent ambulation and maximum gait speed were maintained in the
      intervention group but deteriorated in the control group (p=0.001). Residents
      with both higher and lower cognition benefited in most outcome measures. No
      association was found between improved mobility and reduced risk of falling.
      CONCLUSIONS: Exercise, as part of a fall prevention program, appears to preserve
      the ability to walk, maintain gait speed, ambulate independently, and improve
      step height. Benefits were found in residents with both lower and higher
      cognitive impairment, but were not found to be associated with a reduced risk of
      falling.

PMID- 15575123
TI  - Effect of preventive home visits for ambulatory housebound elders in Japan: a
      pilot study.
AB  - BACKGROUND AND AIMS: Programs of preventive home visits for ambulatory housebound
      elders have not yet become established in Japan. The aim of this randomized pilot
      study was to investigate effects of such visits by public health nurses in Japan.
      METHODS: A randomized controlled study with 18-month follow-up was conducted in a
      small Japanese agricultural town. Participants (n=119) were ambulatory housebound
      elders aged 65 and over, who were able to walk but who went outdoors less than
      three times a week at baseline survey. They were randomly assigned to
      intervention (n=59) or control group (n=60). Intervention group subjects received
      preventive home visits by public health nurses over 18 months (mean home
      visits=4.3). Control group subjects received usual primary and community care.
      Activities of daily living (ADLs), functional capacity, self-efficacy for daily
      activities, self-efficacy for health promotion, depression, and social support
      were collected via questionnaire at baseline and at the 18-month follow-up point.
      RESULTS: At follow-up, 81.4% of intervention group subjects were still living at
      home vs 73.3% of control group subjects (NS). Simple group comparisons following
      repeated measures (ANCOVA) showed that the intervention group had higher ADL
      scores than the control group at follow-up (p=0.044). CONCLUSIONS: These pilot
      results suggest that home visits by public health nurses may be effective in
      helping to reduce ADL decline among ambulatory housebound elders.

PMID- 15575124
TI  - Acute geriatric intervention increases the number of patients able to live at
      home. A prospective randomized study.
AB  - BACKGROUND AND AIMS: In a previous publication, we showed that treatment of
      acutely sick, frail elderly patients in a Geriatric Evaluation and Management
      Unit (GEMU) reduced mortality considerably when compared with the general Medical
      Wards (MW). The aim of this presentation was to study the impact of treatment in
      a GEMU on health care utilization. METHODS: Acutely sick, frail patients, 75
      years or older, who had been admitted as emergencies to the Department of
      Internal Medicine were randomized either to treatment in the GEMU (n=127) or to
      continued treatment in the MW (n=127). While usual treatment was given in the MW,
      the GEMU emphasized interdisciplinary and comprehensive assessment of all
      relevant disorders, early mobilization/rehabilitation, and discharge planning.
      After discharge from hospital, no specific follow-up was offered to any of the
      groups. RESULTS: Of all subjects, 101 (80%) GEMU and 79 (64%) MW patients were
      still living in their own homes at three months (p=0.005); at six months the
      number was 91 (72%) and 74 (60%) (p=0.04) respectively. Median length of index
      stay was 19 days in the GEMU and 13 days in the MW group (p<0.001). After the
      initial stay, there were no statistically significant differences in admissions
      to or time spent in institutions. CONCLUSIONS: The results indicate the overall
      positive treatment effect of acutely sick, frail elderly in a GEMU, i.e. patients
      treated in the GEMU had increased possibilities of living in their own homes, an
      effect that was mainly related to considerably reduced mortality in the GEMU
      group.

PMID- 15575125
TI  - Informal caregiver characteristics and subsequent hospitalization outcomes among
      recipients of care.
AB  - BACKGROUND AND AIMS: It is reasonable to surmise that informal caregivers might
      influence access and use of health services among disabled older adults, although
      this relationship has not been well studied. The objective of this research was
      to examine caregiver attributes with respect to recipients' hospitalization
      experiences. METHODS: Generalized estimating equations were used to generate
      population-average logistic regression models for the risk of incurring inpatient
      hospitalization or being delayed in discharge from hospital. Data come from a
      sample of 420 women aged 65 or older receiving informal care, who participated in
      both the Women's Health and Aging Study and its accompanying Caregiving Survey.
      RESULTS: Individuals whose primary caregivers were characterized by feelings of
      competence in their role were 40% more likely to experience an inpatient
      hospitalization (p<0.05) but 48% less likely to be delayed in discharge from the
      hospital (p<0.05). Measures related to caregiver overload and personal gain were
      not found to be related to the likelihood of either incurring an inpatient
      admission or being delayed in hospital discharge, although individuals whose
      primary caregivers were characterized by role captivity (a measure related to
      perceived burden) were more than twice as likely to be delayed in discharge from
      the hospital (p<0.05) without controlling for other characteristics (p<0.10 in
      the multivariate model). Individuals whose primary caregivers reported being
      involved with recipients' medical professionals were 50% more likely to incur an
      inpatient hospitalization (p<0.01). CONCLUSION: These findings suggest that
      primary caregiver attributes have relevance to recipients' hospitalization
      experiences.

PMID- 15575126
TI  - Management of adverse clinical events by duty physicians in a nursing home.
AB  - BACKGROUND AND AIMS: The nature of adverse clinical events (ACE) during duty
      hours (16:00-08:00 and holidays), as well as the way they are addressed by duty
      physicians (DP) in a nursing home (NH) are the subject of this study. METHODS:
      Data, including medical details concerning ACEs and the resultant referrals to
      hospital, were collected prospectively during 183 consecutive days in a 90-bed
      NH. RESULTS: Ninety-six residents experienced 370 ACEs, representing an average
      of one for every 44.5 patient days. The highest rate of events was during evening
      hours (18:00-21:00). The most prevalent ACE was fever (32%). Most cases (53%)
      were treated by the DPs on site. No intervention was needed in 19% of cases,
      whereas 28% of ACEs (104 cases) were referred to the Emergency Room (ER) of a
      general hospital. Sixty-six percent of these were actually admitted. The rate of
      ER referral of residents was one for every 158 patient days. About 40% of the
      referred patients had been discharged from hospital the previous week. High fever
      was the commonest cause for referral: 47%. During the working hours of the study
      period, the rate of referral by the staff physician was only 1 for every 915
      patient days. Only 17% of these had high fever. CONCLUSIONS: Evening rounds by
      staff physicians, strengthening of working relations with hospital physicians, as
      well as fostering intravenous treatment in NHs, are suggested as means for
      reducing hospital transfers. A standardized method for the reporting of ACEs and
      referrals to hospitals should be adopted in order to facilitate comparisons
      between NHs and to evaluate its use as a quality indicator.

PMID- 15575127
TI  - Pharmacotherapy and blood pressure control in elderly hypertensives in a primary
      care setting in Bahrain.
AB  - BACKGROUND AND AIMS: Antihypertensive treatment in the elderly has important
      beneficial effects in terms of reduced cardiovascular morbidity and mortality.
      The aim of this study was to determine, in elderly hypertensives, the adherence
      of primary care physicians to World Health Organization/International Society of
      Hypertension (WHO/ISH) guidelines for the drug management of hypertension and
      extent of blood pressure (BP) control. METHODS: A multicentric therapeutic audit
      of medical records of elderly hypertensives was performed in nine primary care
      health centers in the Kingdom of Bahrain. RESULTS: In elderly hypertensives (> or
      =60 years), the WHO/ISH-1999 recommended BP targets of <140/<90 mmHg and
      BP<130/85 mmHg were achieved in 11.1% of elderly hypertensives and 4.1% of
      elderly diabetic hypertensives, respectively. Antihypertensive combination
      therapy was used in approximately half of the elderly. No significant difference
      in BP was found in elderly hypertensives treated either with monotherapy or
      combination therapy. As regards mono- and overall drug utilization, beta-blockers
      were the most frequently prescribed drugs in hypertensives, and angiotensin
      converting enzyme (ACE) inhibitors in diabetic hypertensives. Diuretics and
      calcium channel blockers, the preferred antihypertensives for the elderly, were
      less often prescribed, particularly in patients with isolated systolic
      hypertension. CONCLUSIONS: Approximately one out of 9 elderly hypertensives and
      one out of 24 diabetic hypertensives achieved optimal BP control. Although
      preference for antihypertensives was markedly influenced by comorbidity with
      diabetes, tailoring of drug therapy was suboptimal and did not adhere to the
      recommended guidelines in elderly hypertensives. Efforts to improve the drug
      management of hypertension at primary care level, particularly in the elderly,
      are required.

PMID- 15575128
TI  - De facto imprisonment and covert medication use in general nursing homes for
      older people in South East England.
AB  - BACKGROUND AND AIMS: There is growing interest in ethical issues in nursing home
      care, including capacity to consent to residence and covert medication use. This
      study assessed capacity to consent to residence amongst a group of randomly
      selected residents of non-specialist UK nursing homes and examined the prevalence
      of de facto imprisonment and covert medication. METHODS: A cross-sectional
      prevalence study amongst residents in randomly selected non-specialist nursing
      homes in South East England. 445 residents (97 men and 348 women) were randomly
      selected from 157 nursing homes. RESULTS: 14% (64) of the residents interviewed
      lacked the capacity to consent to residence. 6.1% (27) of residents were
      prevented from leaving but less than half of these lacked the mental capacity to
      consent to residence and may be therefore, de facto, unlawfully imprisoned. 4.7%
      (21) of residents on medication had received it covertly in the nursing home.
      CONCLUSIONS: A significant number of residents in the nursing homes studied did
      not appear to have the mental capacity to consent to being there, possibly in
      contravention of the Human Rights Act 1998. There appears to be a small but
      worrying prevalence of de facto imprisonment, and covert medication use in
      residents without severe cognitive impairment.

PMID- 15575129
TI  - Screening for poor performance of lower extremity in primary care: the Camucia
      Project.
AB  - BACKGROUND AND AIMS: Individuals with poor lower extremity performance are prime
      candidates for disability prevention. The Camucia Project is a collaborative
      study between geriatricians and primary care physicians (PCPs) testing the
      hypothesis that PCPs can use a simple performance-based test to identify older
      persons with poor lower extremity function, without excessive interference with
      their clinical routine. We also hypothesized that the number needed to screen
      (NNTS) a positive case would be lower in physicians' clinics than in the general
      population. METHODS: 23 PCPs administered the short physical performance battery
      (SPPB) to 360 consecutive, non-disabled and non-demented, 70- to 79-year-old
      outpatients. PCPs were asked to: 1) evaluate the feasibility and usefulness of
      administering the SPPB; 2) ascertain selected diseases according to predefined
      criteria; 3) identify causes of poor lower extremity function in patients with a
      SPPB score < or =9. NNTS from this study were compared with those estimated in
      non-disabled and non-demented, 70- to 79-year-old persons randomly selected from
      the InCHIANTI study population. RESULTS: The majority of PCPs (20/23) reported
      that using the SPPB to evaluate older patients was feasible and useful. The NNTS
      in the outpatient clinics was lower than in the InCHIANTI participants (1.6 vs
      4.3). Poor lower extremity performance was attributed to musculo-skeletal
      diseases in 75%, to more than one cause in 55% (128/234), and to no specific
      cause in 16.2% (37/234) of the participants with SPPB < or =9. CONCLUSIONS:
      Screening of older persons with poor lower extremity perfomance by PCPs is
      feasible and efficient.

PMID- 15575130
TI  - Spoofing spurious science.

PMID- 15575131
TI  - Including deaf patients in the conversation.

PMID- 15575132
TI  - Rational world a better environment for physicians.

PMID- 15575133
TI  - Accentuating the positive in family medicine.

PMID- 15575134
TI  - Creating the lifestyle you want.

PMID- 15575135
TI  - Put yourself in patients' shoes.

PMID- 15575136
TI  - Crunching the numbers.

PMID- 15575137
TI  - "Listen" article inspires med student.

PMID- 15575138
TI  - Navigating the Medicare Web site.

PMID- 15575139
TI  - Why it's time to purchase an electronic health record system.

PMID- 15575140
TI  - Negotiating your semi-retirement package.

PMID- 15575141
TI  - What motivates staff?

PMID- 15575142
TI  - 5 ways to retain good staff.

PMID- 15575143
TI  - Do you have the right malpractice insurance policy?

PMID- 15575144
TI  - Estimating the risks of coronary angioplasty.

PMID- 15575145
TI  - Starting a practice in a health professional shortage area.

PMID- 15575146
TI  - Dictation reminders.

PMID- 15575147
TI  - Medicare teaching rules.

PMID- 15575148
TI  - Using updates to ease your workday and your mind.

PMID- 15575149
TI  - A multiple-substream unequal error-protection and error-concealment algorithm for
      SPIHT-coded video bitstreams.
AB  - This paper presents a coordinated multiple-substream unequal error-protection and
      error-concealment algorithm for SPIHT-coded bitstreams transmitted over lossy
      channels. In the proposed scheme, we divide the video sequence corresponding to a
      group of pictures into two subsequences and independently encode each subsequence
      using a three-dimensional SPIHT algorithm. We use two different partitioning
      schemes to generate the substreams, each of which offers some advantages under
      the appropriate channel condition. Each substream is protected by an FEC-based
      unequal error-protection algorithm, which assigns unequal forward error
      correction codes to each bit plane. Any information that is lost during the
      transmission for any substream is estimated at the receiver by using the
      correlation between the substreams and the smoothness of the video signal.
      Simulation results show that the proposed multiple-substream UEP algorithm is
      simple, fast, and robust in hostile network conditions, and that the proposed
      error-concealment algorithm can achieve 2-3-dB PSNR gain over the case when error
      concealment is not used at high packet-loss rates.

PMID- 15575150
TI  - Fast-searching algorithm for vector quantization using projection and triangular
      inequality.
AB  - In this paper, a new and fast-searching algorithm for vector quantization is
      presented. Two inequalities, one used for terminating the searching process and
      the other used to delete impossible codewords, are presented to reduce the
      distortion computations. Our algorithm makes use of a vector's features (mean
      value, edge strength, and texture strength) to reject many unlikely codewords
      that cannot be rejected by other available approaches. Experimental results show
      that our algorithm is superior to other algorithms in terms of computing time and
      the number of distortion calculations. Compared with available approaches, our
      method can reduce the computing time and the number of distortion computations
      significantly. Compared with the best method of reducing distortion computation,
      our algorithm can further reduce the number of distortion calculations by 29% to
      58.4%. Compared with the best encoding algorithm for vector quantization, our
      approach also further reduces the computing time by 8% to 47.7%.

PMID- 15575151
TI  - Finding axes of symmetry from potential fields.
AB  - This paper addresses the problem of detecting axes of bilateral symmetry in
      images. In order to achieve robustness to variation in illumination, only edge
      gradient information is used. To overcome the problem of edge breaks, a potential
      field is developed from the edge map which spreads the information in the image
      plane. Pairs of points in the image plane are made to vote for their axes of
      symmetry with some confidence values. To make the method robust to overlapping
      objects, only local features in the form of Taylor coefficients are used for
      quantifying symmetry. We define an axis of symmetry histogram, which is used to
      accumulate the weighted votes for all possible axes of symmetry. To reduce the
      computational complexity of voting, a hashing scheme is proposed, wherein pairs
      of points, whose potential fields are too asymmetric, are pruned by not being
      counted for the vote. Experimental results indicate that the proposed method is
      fairly robust to edge breaks and is able to detect symmetries even when only
      0.05% of the possible pairs are used for voting.

PMID- 15575152
TI  - Grayscale level connectivity: theory and applications.
AB  - A novel notion of connectivity for grayscale images is introduced, defined by
      means of a binary connectivity assigned at image-level sets. In this framework, a
      grayscale image is connected if all level sets below a prespecified threshold are
      connected. The proposed notion is referred to as grayscale level connectivity and
      includes, as special cases, other well-known notions of grayscale connectivity,
      such as fuzzy grayscale connectivity and grayscale blobs. In contrast to those
      approaches, the present framework does not require all image-level sets to be
      connected. Moreover, a connected grayscale object may contain more than one
      regional maximum. Grayscale level connectivity is studied in the rigorous
      framework of connectivity classes. The use of grayscale level connectivity in
      image analysis applications, such as object extraction, image segmentation,
      object-based filtering, and hierarchical image representation, is discussed and
      illustrated.

PMID- 15575153
TI  - Efficient computation of the Hutchinson metric between digitized images.
AB  - The Hutchinson metric is a natural measure of the discrepancy between two images
      for use in fractal image processing. An efficient solution to the problem of
      computing the Hutchinson metric between two arbitrary digitized images is
      considered. The technique proposed here, based on the shape of the objects as
      projected on the digitized screen, can be used as an effective way to establish
      the error between the original and the, possibly compressed, decoded image. To
      test the performance of our method, we apply it to compare pairs of fractal
      objects, as well as to compare real-world images with the corresponding
      reconstructed ones.

PMID- 15575154
TI  - Design of signal-adapted multidimensional lifting scheme for lossy coding.
AB  - This paper proposes a new method for the design of lifting filters to compute a
      multidimensional nonseparable wavelet transform. Our approach is stated in the
      general case, and is illustrated for the 2-D separable and for the quincunx
      images. Results are shown for the JPEG2000 database and for satellite images
      acquired on a quincunx sampling grid. The design of efficient quincunx filters is
      a difficult challenge which has already been addressed for specific cases. Our
      approach enables the design of less expensive filters adapted to the signal
      statistics to enhance the compression efficiency in a more general case. It is
      based on a two-step lifting scheme and joins the lifting theory with Wiener's
      optimization. The prediction step is designed in order to minimize the variance
      of the signal, and the update step is designed in order to minimize a
      reconstruction error. Application for lossy compression shows the performances of
      the method.

PMID- 15575155
TI  - Locally optimum nonlinearities for DCT watermark detection.
AB  - The issue of copyright protection of digital multimedia data has attracted a lot
      of attention during the last decade. An efficient copyright protection method
      that has been gaining popularity is watermarking, i.e., the embedding of a
      signature in a digital document that can be detected only by its rightful owner.
      Watermarks are usually blindly detected using correlating structures, which would
      be optimal in the case of Gaussian data. However, in the case of DCT-domain image
      watermarking, the data is more heavy-tailed and the correlator is clearly
      suboptimal. Nonlinear receivers have been shown to be particularly well suited
      for the detection of weak signals in heavy-tailed noise, as they are locally
      optimal. This motivates the use of the Gaussian-tailed zero-memory nonlinearity,
      as well as the locally optimal Cauchy nonlinearity for the detection of
      watermarks in DCT transformed images. We analyze the performance of these schemes
      theoretically and compare it to that of the traditionally used Gaussian
      correlator, but also to the recently proposed generalized Gaussian detector,
      which outperforms the correlator. The theoretical analysis and the actual
      performance of these systems is assessed through experiments, which verify the
      theoretical analysis and also justify the use of nonlinear structures for
      watermark detection. The performance of the correlator and the nonlinear
      detectors in the presence of quantization is also analyzed, using results from
      dither theory, and also verified experimentally.

PMID- 15575156
TI  - An efficient and anonymous buyer-seller watermarking protocol.
AB  - For the purpose of deterring unauthorized duplication and distribution of
      multimedia contents, a seller may insert a unique digital watermark into each
      copy of the multimedia contents to be sold. When an illegal replica is found in
      the market sometime later, the seller can determine the responsible distributor
      by examining the watermark embedded. However, the accusation against the charged
      distributor, who was the buyer in some earlier transaction, is objectionable
      because the seller also has access to the watermarked copies and, hence, is able
      to release such a replica on her own. In this paper, a watermarking protocol is
      proposed to avoid such difficulties, known as the customer's right problem, in
      the phase of arbitration. The proposed watermarking protocol also provides a fix
      to Memon and Wong's scheme by solving the unbinding problem. In addition, the
      buyer is no longer required to contact the watermark certification authority
      during transactions, and the anonymity of the buyer can be retained through a
      trusted third party. The result is an efficient and anonymous buyer-seller
      watermarking protocol.

PMID- 15575157
TI  - Robust image-adaptive data hiding using erasure and error correction.
AB  - Information-theoretic analyses for data hiding prescribe embedding the hidden
      data in the choice of quantizer for the host data. In this paper, we propose
      practical realizations of this prescription for data hiding in images, with a
      view to hiding large volumes of data with low perceptual degradation. The hidden
      data can be recovered reliably under attacks, such as compression and limited
      amounts of image tampering and image resizing. The three main findings are as
      follows. 1) In order to limit perceivable distortion while hiding large amounts
      of data, hiding schemes must use image-adaptive criteria in addition to
      statistical criteria based on information theory. 2) The use of local criteria to
      choose where to hide data can potentially cause desynchronization of the encoder
      and decoder. This synchronization problem is solved by the use of powerful, but
      simple-to-implement, erasures and errors correcting codes, which also provide
      robustness against a variety of attacks. 3) For simplicity, scalar quantization
      based hiding is employed, even though information-theoretic guidelines prescribe
      vector quantization-based methods. However, an information-theoretic analysis for
      an idealized model is provided to show that scalar quantization-based hiding
      incurs approximately only a 2-dB penalty in terms of resilience to attack.

PMID- 15575158
TI  - Edge detection in ultrasound imagery using the instantaneous coefficient of
      variation.
AB  - The instantaneous coefficient of variation (ICOV) edge detector, based on
      normalized gradient and Laplacian operators, has been proposed for edge detection
      in ultrasound images. In this paper, the edge detection and localization
      performance of the ICOV-squared (ICOVS) detector are examined. First, a
      simplified version of the ICOVS detector, the normalized gradient magnitude
      squared, is scrutinized in order to reveal the statistical performance of edge
      detection and localization in speckled ultrasound imagery. Both the probability
      of detection and the probability of false alarm are evaluated for the detector.
      Edge localization is characterized by the position of the peak and the 3-dB width
      of the detector response. Then, the speckle-edge response of the ICOVS as applied
      to a realistic edge model is studied. Through theoretical analysis, we reveal the
      compensatory effects of the normalized Laplacian operator in the ICOV edge
      detector for edge-localization error. An ICOV-based edge-detection algorithm is
      implemented in which the ICOV detector is embedded in a diffusion coefficient in
      an anisotropic diffusion process. Experiments with real ultrasound images have
      shown that the proposed algorithm is effective in extracting edges in the
      presence of speckle. Quantitatively, the ICOVS provides a lower localization
      error, and qualitatively, a dramatic improvement in edge-detection performance
      over an existing edge-detection method for speckled imagery.

PMID- 15575159
TI  - [Karyotype analysis of Echinocodon lobophyllus].
AB  - The paper reported the chromosome number, karyotype and chromosome volume of
      Echinocodon lobophyllus. The normal diploid was 2n = 16, karyotype formula based
      on Levan's publication was K(2n) = 16= 14m + 2Sm. According to the method of S.
      R. Kuo, the chromosome relative length was 2n = 16 = 10M2 + 6M1, which belong to
      "1A" type according to the Stebbins' karyotype classification. The AS.K% was
      57.24% from Arano's method. The total volume of chromosome groups was 1.16
      microm3.

PMID- 15575160
TI  - [The hygienic examination and quality research of Chinese crude drug scorpion].
AB  - We selected the method of hygienic test to determinate the infection of
      colibacilli, salmonelli, mixed bacteria, mould fungus and yeasts on Chinese crude
      drug scorpion from 29 commerical samples in different storaged period, habitats
      and commerical standard. The results showed there were not colibacilli and
      salmonelli in all 29 samples, but infectious mixed bacteria rate is 100%, which
      is 2.1 times more than salty scorpion in 29 tested samples, and the infectious
      fungi rate is 72.4%. The fungi of salty scorpion is 15% more than fresh scorpion.
      The quantity of infected yeasts on salty scorpion is much more than scorpion.
      There are 4 species of fungi such as Alternaria neesex Wallroth, Aspergillus
      fumigatus Fresenius, Nocarcia sp. and Tricophyton violaceum Sabouraud. Because of
      infectious pathogenic bacteria rate is so high, we suggest to increase the item
      of hygienic test to control the quality of crude drug scorpion and strengthen the
      administration of commerical drugs, so as to reduce the contaminative condition.

PMID- 15575161
TI  - [Comparing identification of 3 kinds of flos chrysanthemi on surface morphology].
AB  - OBJECTIVE: To identify 3 kinds of commodities of famous traditional Chinese
      medicine flos chrysanthemi (FD) from different habitats. METHOD: The surface
      morphology of each part of Hangbaiju produced in Zhejiang province was studied
      and compared with other 2 kinds of FD. RESULT: The intricate morphology
      characters of each part of Hanbaiju were found. There are differences in very few
      characters though Hangbaiju, Gongju and Ganju are very similar in the surface
      morphology. CONCLUSION: The result would be useful to identify flos chrysanthemi.

PMID- 15575162
TI  - [Morphological, microscopical and UV spectral identification of herba visci
      ovalifolii].
AB  - OBJECTIVE: To identify herba Visci ovalifolii, Chinese medicinal materials used
      in Li and Miao nationalities. METHODS: Morphological, microscopical and UV
      spectral methods. RESULT: Dichotomous branch with a yellow surface, with leaf of
      3-5 acrodromous veins originating at the base of the leaf. In transverse section,
      the thick outer wall of the epidermis of stem projecting like nipple; stone cells
      contain frequently a prismatic crystal of calcium oxalate, often occur in the
      cortex and phloem of the stem. Pericycle fibres and xylem fibres all with a well
      developed thick wall; vessels with a bordered pits somtimes have a spiral
      thickened interwall; mesophyll homogeneous contain cluster crystals (not calcium
      oxalate); stomata present on both surfaces, mostly paracrytic, with small and
      narrow subsidiary cells. Hairs absent at the surface. CONCLUSION: Above
      morphological and microscopical characters may be used for the identification of
      herba Visci ovalifolii. UV spectral method is a simple identificating method for
      herba Visci ovalifolii.

PMID- 15575163
TI  - [Effect of radix angelicae sinensis decoction for supplementing blood on
      inhibiting the increase of endothelial cell monolayer permeability induced by
      hypoosmotic solution].
AB  - OBJECTIVE: To study effect of radix Angelicae sinensis decoction for
      supplementing blood (RASDSB) on inhibiting the increase of endothelial cell
      monolayer permeability induced by hypoosmotic solution. METHODS: The endothelial
      cells isolated from newborn bovine aorta were cultured on polycarbonate
      microporous filter membrane to develop compact endothelial monolayer. Fluid
      filtration coefficient (Kf), filtration volume (Jv) and osmotic reflective
      coefficient (sigma) to protein of the endothelial monolayer were measured treated
      by hypoosmotic solution (changing concentration of serum in M199 solution from
      20% to 2%) for 120 min or by hypoosmotic solution containing 10(-4) g x ml(-1)
      RASDSB for 120 min after perfused Hanks balanced salt solution containing 5 g x
      L(-1) albumin. RESULTS: Kf and Jv of the endothelial monolayer treated by
      hypoosmotic solution increased and sigma of that decreased. RASDSB could inhibit
      above-mentioned change. Morphological analysis demonstrated that RASDSB could
      inhibit widening of intercellular distance and enlargement of cellular area in
      the endothelial monolayer induced by hypoosmolality. CONCLUSION: Hypoosmotic
      solution could increase endothelial cell monolayer permeability and RASDSB could
      inhibit the increase.

PMID- 15575164
TI  - [Serapharmacological effect of kangxian ruangan granula on the proliferation of
      hepatic stellate cells].
AB  - OBJECTIVE: To investigate the antifibrotic mechanism of kangxian ruangan granula
      (KXRGG) at cellular level. METHOD: HSC were isolated from the normal rats by
      enzyme digestion and density gradient centrifugation, cultured, identified and
      subcultured. The medicated sera were prepared to incubated with the subcultured
      HSC. Sodium chloride sera and colchicines sera were taken as control groups. HSC
      viability was observed by 3H-proline; cell proliferation was measured with 3H-TdR
      incorporation and MTT colorimetric assay. RESULT: KXRGG medicated serum had no
      effect on the cellular shape and elevated 3H-proline incorporation (P < 0.01).
      Drug serum obviously inhibited 3H-TdR incorporation and MTT transformation (P <
      0.01), and the latter had a drug concentration-dependent tendency. CONCLUSIONS:
      KXRGG can elevate cellular viability and has no toxic effect. The formula can
      inhibit the proliferation of HSC, which may be one of the cellular mechanisms of
      its antifibrotic action.

PMID- 15575165
TI  - [Regulation on the immunological effect of mogrosides in mice].
AB  - OBJECTIVE: To investigate the cellular immunological effect of mogrosides in
      mice. METHODS: Mogrosides was administered to normal or CTX-induced
      immunosuppressive mice, and their macrophage function and T lymphocyte
      proliferation were detected. RESULTS: Mogrosides could promote phagocytosis and T
      lymphocyte proliferation significantly in the CTX-induced immunosuppressive mice,
      but not in the normal mice. CONCLUSION: The results suggested that mogrosides had
      certain up-regulation on cellular immunity in the CTX-induced immunosuppressive
      mice.

PMID- 15575166
TI  - [Study on anticonvulsive effect of rhizoma pinelliae].
AB  - Anticonvulsive effect of water-soluble extract of rhizoma Pinelliae was studied.
      The result showed that the extract of rhizoma Pinelliae could remarkably inhibit
      the convulsion induced by strychnine and obviously reduce mortality rate in mice.
      But the extract could be destroyed easily by heat.

PMID- 15575167
TI  - [Study on extraction process of aqueous part of radix Salvia miltiorrhiza].
AB  - OBJECTIVE: To find out the optimum extraction process for total salvianolic acid
      part of radix Salviae miltiorrhizae. METHOD: The extraction process was studied
      by orthogonal design with the danshen su content determined by RP-HPLC as index.
      RESULT: A3B3C2D1 is the best extraction condition of aqueous part from radix
      Salvia miltiorrhiza. CONCLUSION: This extraction process shows total salvianolic
      acid has high content and good stability.

PMID- 15575168
TI  - [Studies on extraction process of Phyllanthus urinaria].
AB  - OBJECTIVE: To optimize the extraction process of Phyllanthus urinaria L. METHOD:
      The optimum extraction condition was investigated by the orthogonal design in
      flavonoids content as index. RESULTS: The factors influencing extraction
      efficiency were as follows: D > A > B> C (A: Concentration of ethanol, B: The
      amount of ethanol added, C: Time of extraction, D: Times of extraction). The
      optimum extraction condition was: extracting the drug for 3 times, every time for
      2 hour, after adding 8 fold of ethanol, utilizing concentration of ethanol for
      70%. CONCLUSION: The optimized process is stable and high efficient.

PMID- 15575169
TI  - [A herbalogical study on traditional Mongolian medicine "lideri"].
AB  - By herbalogical study and investigation, "lideri" used by Mongolia doctors in
      different areas mainly contains 10 species from 4 genera of 4 families, but the
      quality materials only contains 3 species, Tinospora sinensis (Lour.) Merr., T.
      cordifolia Miers and T. capillipes Gagnep.

PMID- 15575170
TI  - [Analysis of tendency of false and inferior species from Chinese medicinal
      materials markets].
AB  - OBJECTIVE: To offer information on the supervision by analysing the change of
      origin of false and inferior species from Chinese medicinal materials (CMM)
      markets. METHOD: 750 cases false and inferior species from Hubei province were
      compared classifiedly. RESULTS: In recent ten years, distributive characteristics
      of false and inferior species from CMM markets is as follows. First, false and
      inferior species from prepared medicinal herb increase, so do with man-made
      adulteration and poisonous species. Second, false and inferior species increase
      in rural area, country fairs, individual clinics and medicine booths. Last,
      extracted products are sold and used as certified products. CONCLUSION: CMM
      country fairs, outlying rural area, individual clinics and private medicine
      booths are the center of further supervision hereafter.

PMID- 15575171
TI  - Health-economic comparison of three recommended drugs for the treatment of
      osteoporosis.
AB  - Osteoporosis is a large and growing disease with significant health consequences.
      Based on an evaluation of clinical evidence, the German osteology umbrella
      organization DVO (Dachverband Osteologie deutschsprachiger wissenschaftlicher
      Fachgesellschaften) published guidelines in March 2003 for the diagnosis and
      treatment of osteoporosis. For prevention of fractures in women with
      postmenopausal and senile osteoporosis, these guidelines recommend three
      treatment options as first-line therapy: risedronate, alendronate and raloxifene.
      No evidence is currently available for the reduction of hip fractures by
      raloxifene. Only risedronate and alendronate, therefore, are recommended for
      prevention of hip fractures. Information on the cost-effectiveness of preventing
      and treating osteoporosis may support decision makers in more efficient
      allocation of resources. Accordingly, the objective of this study is the
      comparative assessment of the cost-effectiveness of risedronate, alendronate and
      raloxifene for patient populations in Germany at high risk of osteoporotic
      fracture due to low bone mineral density (BMD) (i.e., T-score < -2.5) and
      resulting from a history of at least one previous vertebral fracture, as compared
      to osteoporotic patients with no treatment. Target variables for the economic
      comparison are costs per hip fracture avoided and costs per quality-adjusted life
      year (QALY) gained. Hip fractures are the most costly and best-documented
      complication of osteoporosis. A cost-effectiveness analysis was therefore
      conducted, using as criteria for evaluating intervention the incremental cost per
      hip fracture avoided and the cost per QALY gained. We used a fracture-incidence
      based Markov model of osteoporosis, with analysis of patients' transition across
      outcome states over time (e.g., fracture, healthy, dead). Base-case analysis was
      conducted on a cohort of 1,000 women aged 70 with low spine BMD and prevalent
      vertebral fracture, over 3 years of treatment with risedronate, alendronate or
      raloxifene, and with application of a 10-year analytic time horizon. Model inputs
      included hip and vertebral fracture incidence rates; relative risk of fracture
      given low BMD and prevalent vertebral fracture, fracture cost, treatment
      prices/day (risedronate: 35 mg, 1.76 euro; alendronate: 70 mg, 1.82 euro;
      raloxifene: 60 mg, 1.82 euro); health utility; and efficacy in terms of relative
      risk reduction of fracture of the hip (60% risedronate; 51% alendronate; not
      significant raloxifene) and vertebrae (49% risedronate; 47% alendronate; 30%
      raloxifene). A 5% discount rate was applied to cost and outcomes. In the base
      case, treatment with risedronate reduces costs from the social insurance
      perspective with respect to both endpoints: i.e., costs per averted hip fracture
      and QALY. Over the 3-year treatment period and 10-year observation, furthermore,
      risedronate proved superior to alendronate and raloxifene (i.e., risedronate was
      less expensive and more effective). From the perspective of statutory health
      insurance, the cost per averted hip fracture is 37,348 euro for risedronate and
      48,349 euro for alendronate (costs for raloxifene were not calculated due to a
      nonsignificant effect on prevention of hip fractures); and cost per QALY gained
      is 32,092 euro for risedronate, in comparison to patients in Germany with no
      therapy (alendronate 41,302 euro; raloxifene 1,247,119 euro). This cost
      effectiveness analysis gives evidence that bisphosphonates are cost effective.
      Under consideration of current prices and the published clinical evidence,
      risedronate dominates the comparison of DVO-recommended drugs.

PMID- 15575172
TI  - Calcipotriol in the treatment of childhood vitiligo.
AB  - Eighteen patients with a clinical diagnosis of vitiligo, aged between three and
      12 years (mean 8.9 years), were enrolled in this study in order to evaluate the
      efficacy and tolerability of topical calcipotriol in the treatment of childhood
      vitiligo. Six patients (33.3%) were males and 12 were females (66.7%). Fourteen
      patients (77.8%) had focal vitiligo, two (11.1%) had mucosal vitiligo and two
      (11.1%) had segmental vitiligo. The face was involved in 11 patients (61.1%). The
      treatment was applied twice daily as 50 microg/gm cream in nine patients and as
      ointment in the remaining patients. Treatment assessment was carried out
      clinically at 2 weeks, and then monthly for 4-6 months. Four patients (28.6%)
      were excluded from the study (one due to irritation and three due to lost contact
      in follow-up). Fourteen patients (71.4%) completed the treatment course (> 3
      months). Of the treated patients, ten (77.8%) showed improvement and four
      patients (22.2%) had no response. Among responders, three patients (21.4%) showed
      complete resolution, four (28.6%) showed 50%-80% improvement and three patients
      (21.4%) showed 30% to < 50% improvement. Only one patient (5.5%) developed
      irritation. In conclusion, calcipotriol is an effective treatment in vitiligo.
      Better results are obtained with ointment than with cream. Calcipotriol can be
      helpful in children in whom potent steroids and PUVA are not advisable.

PMID- 15575173
TI  - Accelerated cardiomyopathy in maternally inherited diabetes and deafness.
AB  - The clinical features and course of cardiac involvement in a patient with
      maternally inherited diabetes and deafness associated with the mitochondrial DNA
      3243 mutation are reported. A 45-year-old woman with maternally transmitted
      diabetes mellitus and deafness presented with congestive heart failure. The
      patient showed a short P-R interval on electrocardiogram (ECG) and had developed
      progression from left ventricular hypertrophy to a hypokinetic cardiomyopathy
      pattern over the course of 10 months. Rapid cardiac change was accompanied by
      left ventricular remodeling, as shown by wall thinning on echocardiogram and
      decrease in QRS voltages on ECG. Coronary arteriography revealed no significant
      stenosis. In the endomyocardial biopsy specimens, light microscopy showed
      nonspecific cardiomyopathic changes. Genetic testing for mitochondrial DNA
      mutations in peripheral blood lymphocytes revealed an adenine (A)-to-guanine (G)
      substitution at nucleotide 3243 in the mitochondrial DNA encoding the transfer
      RNA for leucine (tRNA Leu (UUR)). The proportion of mutant mitochondrial DNA was
      25%. Two of the patient's daughters, aged 13 and 21 years, who were symptom free,
      were found to carry the same point mutation. A short P-R interval on ECG in the
      younger of them was the sole manifestation of the mutation. Unfortunately, 6
      months after diagnosis, the patient died suddenly at home. Accelerated
      cardiomyopathy can occur as a mitochondria-related complication in patients with
      maternally inherited diabetes and deafness associated with the 3243 mutation.

PMID- 15575174
TI  - An evaluation of nursing care in cancer patients.
AB  - The aim of the present study was to identify what hospitalized cancer patients
      expect from nurses in terms of the care they receive. The specific aims of this
      study were: (i) to identify those individuals to whom the patients felt closest
      in the hospital setting and (ii) to evaluate nurses' management of cancer
      patients during their stay in the hospital. The sample included patients
      hospitalized at Ege University Hospital and Suat Seren District Hospital, Izmir,
      Turkey. We found significant differences between the scores of satisfaction and
      dissatisfaction and gender age, education, occupation, type of cancer and the
      mode of treatment (p < 0.05). The majority of the cancer patients reported that
      nursing management was unsatisfactory. Some demographic factors such as cultural
      and social status affected patients' expectations.

PMID- 15575175
TI  - Analysis of job-related risks faced by hospital nurses.
AB  - The aim of this study was to analyze the job-related risks nurses face during
      training such as needle-stick injuries, contaminated blood and infectious fluids.
      From May to July 2003 we conducted a survey of a sample of 242 nurses who were
      working in the the Pediatric Hospital, Government Hospital, the Training Hospital
      of Celal Bayar University, the Gynecology Hospital and the Psychiatric Hospital
      in Manisa City in Turkey. Two hundred sixteen nurses (89.3%) had needlestick
      injuries and 107 (44.2%) had injuries by contaminated cutting utensils. A total
      of 104 nurses (43.0%) used gloves, while 65 (26.9%) used gloves and mask. In
      medical and surgical staff nurses, injuries due to contaminated cutting utensils
      were statistically significant (p < 0.05). Awareness of accidents was significant
      between the two groups (p < 0.05).

PMID- 15575176
TI  - Environmental threats, mitigation strategies and high-mountain areas.
AB  - High-mountain areas suffer from increasing environmental threats. The causes are
      often global in dimension but lead to specific impacts under conditions of steep
      and/or high-altitude terrain with strong effects from snow and ice. This paper
      presents a global perspective, focussing primarily on observed and projected
      changes in climate and then goes on to discuss key messages of greatest relevance
      to the highest belts of mountain regions. The paper finishes with a brief
      discussion of mitigation strategies.

PMID- 15575177
TI  - Mountain biodiversity, its causes and function.
AB  - The personal safety and well-being of one fifth, and water supply for almost half
      of all people depend directly or indirectly on the functional integrity of
      mountain ecosystems, the key component of which is a robust vegetation cover. The
      green 'coat' of the world's mountains is composed of specialized plants, animals
      and microbes, all nested in a great variety of microhabitats. Because a single
      mountain may host a series of climatically different life zones over short
      elevational distances, mountains are hot spots of biodiversity and priority
      regions for conservation. With their diverse root systems, plants anchor soils on
      slopes and prevent erosion. Both landuse and atmospheric changes such as elevated
      CO2 and climatic warming affect mountain biodiversity. Sustained catchment value
      depends on sustained soil integrity, which in turn depends on a diverse plant
      cover. Whether landuse in mountains is sustainable is a question of its
      consequences for water yield and biodiversity. Given their dependence on
      mountains, lowlanders should show concern for the highlands beyond their
      recreational value.

PMID- 15575178
TI  - Matching traditional and scientific observations to detect environmental change:
      a discussion on Arctic terrestrial ecosystems.
AB  - Recent environmental changes are having, and are expected to continue to have,
      significant impacts in the Arctic as elsewhere in the world. Detecting those
      changes and determining the mechanisms that cause them are far from trivial
      problems. The use of multiple methods of observation can increase confidence in
      individual observations, broaden the scope of information available about
      environmental change, and contribute to insights concerning mechanisms of change.
      In this paper, we examine the ways that using traditional ecological knowledge
      (TEK) together with scientific observations can achieve these objectives. A
      review of TEK observations in comparison with scientific observations
      demonstrates the promise of this approach, while also revealing several
      challenges to putting it into practice on a large scale. Further efforts are
      suggested, particularly in undertaking collaborative projects designed to produce
      parallel observations that can be readily compared and analyzed in greater detail
      than is possible in an opportunistic sample.

PMID- 15575179
TI  - Mountain biodiversity patterns at low and high latitudes.
AB  - This paper presents an overview of mountain biodiversity at a multitude of scales
      in space, time, and function. Even though species richness is usually the focal
      component in nature conservation, genetic diversity within species is equally
      important. The small-scale distribution of species in the tropical Andes, as
      exemplified by the plant genera Calceolaria and Bartsia, contrasts against the
      situation in high-latitude mountains, e.g., the Scandes, where species have wide
      ranges and many are circumpolar. Recent studies on alpine plants based on
      molecular methods show that the intraspecific genetic diversity tends to increase
      with latitude, a situation brought about by the glaciation history with repeated
      contraction-expansion episodes of species' distributions. In tropical mountains,
      species distributions are geographically much narrower, often as a result of
      relatively recent, local speciation. Thus, whereas species richness in mountains
      decreases from the Equator towards the poles, genetic diversity shows the
      opposite trend. Finally, a comparison of ecosystem diversity in low- and high
      latitude mountain ranges (tropical Andes vs. Scandes) shows that the landscapes
      differ profoundly with regard to timberline ecotones, snow distribution, and
      climate variables, and are subject to widely different impacts of global change

PMID- 15575180
TI  - Mountains of the world: vulnerable water towers for the 21st century.
AB  - Mountains as "Water Towers" play an important role for the surrounding lowlands.
      This is particularly true of the world's semiarid and arid zones, where the
      contributions of mountains to total discharge are 50-90%. Taking into account the
      increasing water scarcity in these regions, especially for irrigation and food
      production, then today's state of knowledge in mountain hydrology makes
      sustainable water management and an assessment of vulnerability quite difficult.
      Following the IPCC report, the zone of maximum temperature increase in a 2 x CO2
      state extends from low elevation in the arctic and sub-arctic to high elevation
      in the tropics and subtropics. The planned GCOS climate stations do not reach
      this elevation of high temperature change, although there are many high mountain
      peaks with the necessary sensitive and vulnerable ecosystems. Worldwide, more
      than 700 million people live in mountain areas, of these, 625 million are in
      developing countries. Probably more than half of these 625 million people are
      vulnerable to food insecurity. Consequences of this insecurity can be emigration
      or overuse of mountain ecosystems. Overuse of the ecosystems will, ultimately,
      have negative effects on the environment and especially on water resources. New
      research initiatives and new high mountain observatories are needed in order to
      understand the ongoing natural and human processes and their impacts on the
      adjacent lowlands.

PMID- 15575181
TI  - Mountains: top down.
AB  - Mountainous regions offer not only essential habitat and resources, including
      water, to the earth's more than 6 billion inhabitants, but also insights into how
      the global human habitat works, how it is being changed at the moment as global
      climates are disrupted, and how the disruption may lead to global biotic and
      economic impoverishment. At least 600 million of the earth's more than 6 billion
      humans dwell in mountainous regions. Such regions feed water into all the major
      rivers of the world whose valleys support most of the rest of us. At least half
      of the valley dwellers receive part or all of their water from montane sources,
      many from the melt water of glaciers, others from the annual snow melt. Glaciers
      are retreating globally as the earth warms as a result of human-caused changes in
      the composition of the atmosphere. Many are disappearing, a change that threatens
      municipal water supplies virtually globally. The warming is greatest in the
      higher latitudes where the largest glaciers such as those of Greenland and the
      Antarctic Continent have become vulnerable. The melting of ice in the northern
      hemisphere raises serious concerns about the continued flow of the Gulf Stream
      and the possibility of massive climatic changes in Scandinavia and northern
      Europe. Mountains are also biotic islands in the sea life, rich in endemism at
      the ecotype level. The systematic warming of the earth changes the environment
      out from under these genetically specialized strains (ecotypes) which are then
      maladapted and vulnerable to diseases of all types. The process is systematic
      impoverishment in the pattern conspicuous on mountain slopes with increasing
      exposure to climatic extremes. It is seen now in the increased mortality and
      morbidity of plants as climatic changes accumulate. The seriousness of the global
      climatic disruption is especially clear in any consideration of mountains. It can
      and must be addressed constructively despite the adamancy of the current US
      administration.

PMID- 15575182
TI  - Environmental changes in the North Atlantic Region: SCANNET as a collaborative
      approach for documenting, understanding and predicting changes.
AB  - The lands surrounding the North Atlantic Region (the SCANNET Region) cover a wide
      range of climate regimes, physical environments and availability of natural
      resources. Except in the extreme North, they have supported human populations and
      various cultures since at least the end of the last ice age. However, the region
      is also important at a wider geographical scale in that it influences the global
      climate and supports animals that migrate between the Arctic and all the other
      continents of the world. Climate, environment and land use in the region are
      changing rapidly and projections suggest that global warming will be amplified
      there while increasing land use might dramatically reduce the remaining
      wilderness areas. Because much of the region is sparsely populated--if populated
      at all--observational records of past environmental changes and their impacts are
      both few and of short duration. However, it is becoming very important to record
      the changes that are now in progress, to understand the drivers of these changes,
      and to predict future consequences of the changes. To facilitate research into
      understanding impacts of global change on the lands of the North Atlantic
      Regions, and also to monitor changes in real time, an EU-funded network of
      research sites and infrastructures was formed in 2000: this was called SCANNET-
      SCANdinavian/North European NETwork of Terrestrial Field Bases. SCANNET currently
      consists of 9 core sites and 5 sites within local networks that together cover
      the broad range of current climate and predicted change in the region. Climate
      observations are well replicated across the network, whereas each site has tended
      to select particular environmental and ecological subjects for intensive
      observation. This provides diversity of both subject coverage and expertise. In
      this paper, we summarize the findings of SCANNET to-date and outline its
      information bases in order to increase awareness of data on environmental change
      in the North Atlantic Region. We also identify important gaps in our
      understanding and identify where the roles of existing infrastructures and
      activities represented by SCANNET can facilitate future research, monitoring and
      ground-truthing activities.

PMID- 15575183
TI  - The Alps and the imagination.
AB  - In the late 19th century, mountaineer and essayist Sir Leslie Stephen wrote that
      the Alps were "Europe's Playground." His words were prescient: the Alps are today
      one of the continent's most valued recreation areas. However, the importance of
      Stephen's words can only be appreciated when set in historical context. One
      hundred years earlier, his remark would have been laughed at. Until the late 18th
      century the Alps were a source of fear to travellers and of mystery to
      scientists. They were an uncharted wilderness at the heart of the world's most
      crowded continent. Yet, within a remarkably short space of time, they were
      mapped, developed and exploited. Their current status as "playground" is bound
      intrinsically to a shift in imagination, beginning in the 16th century and
      accelerating dramatically between the years 1800 and 1914, that has transformed
      them, in popular perception, from a realm of terror and superstition to one of
      beauty, relaxation and contemplation. Driven by fresh perspectives in the fields
      of science, music, literature and aesthetics, the metamorphosis has affected our
      appreciation not only of the Alps but of every mountain range in the world.

PMID- 15575184
TI  - Mountains as an existential resource, expression in religion, environment and
      culture.

PMID- 15575185
TI  - What if we could start over?

PMID- 15575186
TI  - Evidence-based protocol: oral hygiene care for functionally dependent and
      cognitively impaired older adults.

PMID- 15575187
TI  - Prevalence rate of pressure ulcers in California nursing homes: using the OSCAR
      database to develop a risk-adjustment model.

PMID- 15575188
TI  - Unrecognized chronic dehydration in older adults: examining prevalence rate and
      risk factors.
AB  - Dehydration has serious consequences for older adults, including increased risk
      of illness or death. This retrospective review of medical records describes the
      prevalence, assessment, and risk factors for chronic dehydration in 185 older
      adults who visited an emergency department in June 2000. Results showed chronic
      dehydration was present in 89 (48%) patients. Physicians documented assessment
      for signs of dehydration in 23 (26%) of the dehydrated older adults, but no
      independent assessments for dehydration were recorded by nurses. These findings
      indicate many older adults may suffer from unrecognized dehydration, and nurses
      should be alert to the possibility that dehydration may be present in community
      dwelling older adults as well as those who live in residential facilities.

PMID- 15575189
TI  - Older adults and autonomy in acute care: increasing patients' independence and
      control during hospitalization.
AB  - In a grounded theory study of the experience and actions of hospitalized older
      adults, autonomy emerged as a major focus, particularly during the last phase of
      hospitalization. Autonomy, defined in the derived theory as older adults' freedom
      and ability to act on their own behalf, has two components: independence (the
      physical ability to act) and control (the ability to make decisions on one's own
      behalf). Being in the hospital threatens the autonomy of older adults. This
      article describes changes in the autonomy of older adults throughout
      hospitalization and makes recommendations for improving their autonomy through
      acute care hospital system redesign.

PMID- 15575190
TI  - Expectations for care: older adults' satisfaction with and trust in health care
      providers.
AB  - This study sought to determine whether community-dwelling older adults'
      expectations for care were met by identifying factors that influence trust in and
      satisfaction with health care providers. Data were collected using a demographic
      questionnaire and focus group methodology. A total of 39 older adults
      participated in 8 focus groups. Three categories of themes were identified: a
      sense of personal touch, technical proficiency, and environmental factors. These
      categories related to individual providers or practice environments. When
      providers and practice settings met expectations for care, then the elderly
      individual was satisfied. Trust was more complex, as the older adults indicated
      they could be satisfied but not trust providers or they could trust providers but
      not be satisfied. Implications for practice include spending quality time with
      older adults and treating them as individuals.

PMID- 15575191
TI  - Reducing the incidence of pressure ulcers: implementation of a turn-team nursing
      program.
AB  - This study examined the effects a structured program designed to reduce pressure
      ulcers among patients in a midsized geriatric hospital. A select group of
      caregivers were organized into a "turn team that was responsible for preventive
      pressure ulcer care. Patient and staff data were collected during 6-month trial
      period. Subsequent analysis showed patient referrals to the staff enterostomal
      nurse and average length of stay, as well compensable musculoskeletal injuries
      among all staff declined. In addition, concerns the program might lead to an
      increased incidence of nosocomial infections were not substantiated.

PMID- 15575192
TI  - The legacy.

PMID- 15575193
TI  - [Study on the superfine comminution of traditional Chinese medicine].
AB  - This paper has introduced the terms, concept and characteristics of superfine
      comminution of traditional Chinese medicine. The progress in the study on the
      superfine comminution of the single drug and compound prescription was analyzed,
      and work principles of equipment in common use for superfine comminution were
      outlined. The future application of superfine comminution technique in
      traditional Chinese medicine was forecast and the problems that should be solved
      during the future research work were also pointed out in the paper.

PMID- 15575194
TI  - [Tumor multidrug-resistance and reversing actions of traditional Chinese
      medicine].
AB  - Tumor multidrug-resistance (MDR) is a major factor in chemotherapeutic failure.
      In recent years, the development of anti-MDR has become an important focus in
      research. The mechanisms of MDR relate to P-glycoprotein, MRP1, apoptosis, the
      unusual DNA repair, the organic micro-environment, and so on. This review
      summarized the advances in MDR mechanism research. At the same time, it
      summarized the recent research of traditional Chinese medicine in reversing MDR.
      Furthermore, their mechanisms and major features of actions were also discussed.

PMID- 15575195
TI  - [Prevention and treatment of cholelithiasis by traditional Chinese medicine].
AB  - Cholelithiasis is one of the clinically common and frequently encountered
      diseases. In this paper, the Chinese Meteria Medica and prescriptions utilized to
      treat cholelithasis were discussed in four aspects. In addition, we discussed the
      clinical effect and mechanism of actions of these drugs in order to provide some
      reference for future drug development in this area.

PMID- 15575196
TI  - [Selection of sodium chloride tolerant mutants in Chrysanthemum morifolium in
      Anhui].
AB  - OBJECTIVE: To select the sodium chloride tolerant mutants of the Chrysanthemum
      morifolium callus through tissue culture and EMS (ethylmethane sulfonate)
      treatment. METHOD: Calli were induced from the leaves of C. morifolium. The calli
      were treated with 0.2% and 0.5% EMS, respectively. After 15 days' culture, the
      calli were transplanted to selection media with 0.5%, 1.0% and 1.5% NaCl, and the
      sodium chloride tolerant mutants were selected out. RESULT AND CONCLUSION: After
      tested the sodium chloride tolerant stability, the callus selected are found to
      be the mutants indeed.

PMID- 15575197
TI  - [Studies on sex identification and variation of endogenous hormones in female and
      male plants of Gynostemma pentaphyllum].
AB  - OBJECTIVE: To distinguish female and male plants of Gynostemma pentaphyllum
      quickly and accurately in the stage of seedling and to understand the relation
      between sex differentiation and endogenous plant hormone. METHOD: Stained methods
      of BTB and enzyme linked immuno-sorbent Assay were used. RESULT: 10 Hours after
      being dyed, the liquid extract of female plants turned into yellow, while extract
      of male ones turned green. There were obvious differences on iPAs and GA(1 + 3)
      contents but no differences on IAA and ABA contents between male and female
      plants during the stages of seedling and vegetative growth. CONCLUSION: BTB can
      be used for distinguishing female and male plants and there were a certain
      relation between sex and endogenous plant hormones.

PMID- 15575198
TI  - [Determination of gentiopicroside in different morphological types of cultivated
      Gentiana manshurica population].
AB  - OBJECTIVE: To study the correlation between morphological variation and
      gentiopicroside content in cultivated Gentiana manshurica roots and to
      investigate the feasibility of breeding new varieties of high effective
      constituent content. METHOD: Gentiopicroside was determined in 5 morphological
      types of cultivated G. manshurica roots by HPLC, which are normal (or wild) type,
      white-flowered type, thick-rooted type, broad-leaved type I and broad-leaved type
      II. RESULT: Among different types gentiopicroside content is the highest in the
      roots of thick-rooted type, the contents decrease as following order: normal
      type, broad-leaved type I white-flowered type and broad-leaved type II, and the
      gentiopicroside contents in the same type root system are a positive correlation
      with root ages, as 3-years-age roots > 2-years-age roots > 1-year-age varied with
      roots. CONCLUSION: The contents of effective constituent vary with the
      morphological variation in cultivated G. manshurica. It is feasible to breed a
      new variety with high effective constituent with the morphological character as a
      selecting index.

PMID- 15575199
TI  - [Content of inorganic elements of Salvia miltiorrhiza root in different area and
      physicochemical properties of its growing soil].
AB  - OBJECTIVE: To provide basis of environmental factors of genuine crude drug,
      Salvia miltiorrhiza root. METHOD: On-the-spot investigation and indoor chemical
      analysis were made to study the physicochemical properties of growing soil and
      content of inorganic elements of S. miltiorrhiza, and obtained data were analysed
      with SPSS 10.0 software. RESULT: S. miltiorrhiza root of high harvest area
      accumulated Cu and Zn. In soil principal component analysis, no principal
      component was obvious. So the drug has good adaptability in ecological
      environment of soil. CONCLUSION: Ecological environment of soil isn't leading
      factor in forming genuine crude S. miltiorrhiza.

PMID- 15575200
TI  - [Comparison on ingredients between cultured cell and cultivated Saffron pistils].
AB  - OBJECTIVE: To compare the differences of active ingredients between tissue
      cultured cells and cultivated saffron pistils. METHOD: The experiment was carried
      out by the Fourier transform infrared spectroscopy (FTIR) spectra and high
      performance liquid chromatography (HPLC). RESULT: The data indicated that the
      species and contents active ingredients in saffron pistils from different places
      were different. The species of active ingredients in tissue cultured cells are
      less than those in cultivated saffron pistils. However, the quantity of crocin A,
      which showed good anticancer effect, is 2-3 times more than that in cultivated
      saffron pistils. CONCLUSION: The active ingredients of the tissue cultured cells
      are similar to those of saffron pistils, but their contents are different.
      Therefore, the tissue cultured cells can only be the part-substitutes of
      cultivated saffron pistils.

PMID- 15575201
TI  - [Study on adsorption of danshen water-soluble compounds with macroporous resin
      D301].
AB  - OBJECTIVE: To study the adsorption and enrichment of effective compounds of
      danshensu, and protocatechualdehyde from Danshen water extracts by macroporous
      resin D301. METHOD: The change of active compounds was observed by detecting the
      amount of danshensu and protocatechualdehyde with HPLC. RESULT AND CONCLUSION:
      Macroporous resins D301 can be used in the process of adsorbing and purifying
      active compounds of danshensu and protocatechualdehyde, and increase the amount
      of active compounds in water extracts.

PMID- 15575202
TI  - [Study on the SFE condition for curcumin in Curcuma longa].
AB  - OBJECTIVE: To optimize the conditions of supercritical fluid extraction (SFE) for
      curcumin in Curcuma longa. METHOD: Optimum extraction conditions were studied by
      orthogonal tests. The extracts were analyzed by HPLC. RESULT: The optimal
      extraction conditions were pressure 25 MPa, temperature 55 degrees C, static time
      4 h, dynamic time 5 h, flow rate of CO2 3.5 L x min(-1), co-solvent ethanol 30%
      (mL x g(-1)). CONCLUSION: It is feasible to extract curcumin by SFE.

PMID- 15575203
TI  - [Determination of luteolin-7-O-glycoside in the herb of Dracocephalum rupestra by
      HPLC].
AB  - OBJECTIVE: To develop a method for determination of luteolin-7-O-glycoside in the
      roots, stems, leafs, flowers and aerial parts of Dracocephalum rupestra sampled
      in different seasons. METHOD: The samples were analyzed on an phenomenex C18
      column, with mobile phase of methanol-acetonitrile-0.4% phosphoric acid (30:8:62)
      at flow rate 1.0 mL x min(-1) and detection at wavelength of 350 nm. RESULT: The
      content of luteolin-7-O-glycoside in different parts of D. rupestra was different
      maximum in leaves, while minimum in stems. Luteolin-7-O-glycoside in D. rupestra
      sampled before blossoming was the highest. CONCLUSION: The method simple,
      accurate and suitable for the quality evaluation of this plant medicine.

PMID- 15575204
TI  - [Isolation and elucidation of antioxidant constituents from acetone extract in
      root of Scutellaria rehderiana].
AB  - OBJECTIVE: To isolatate and elucidate the antioxidant constituents from acetone
      extract of Scutellaria rehderiana. METHOD: Chemical constituents were isolated by
      several column chromatographies and their structures were elucidated on the basis
      of standard compounds and spectral analysis. RESULT: Five compounds, oroxylin A,
      wogonin, baicalein, ganhuangenin, ganhuangemin were isolated from acetone extract
      of S. rehderiana. Baicalin was obtained from methanol extract of S. rehderiana.
      CONCLUSION: Ganhuangemin was isolated from the plant for the first time.
      Baicalein and ganhuangenin have stronger antioxidant activity than that of BHT
      (butylated hydroxytoluene).

PMID- 15575205
TI  - [Studies on chemical constituents in dried buds of Lonicera confusa].
AB  - OBJECTIVE: To investigate the chemical constituents of the dried buds of Lonicera
      confusa. METHOD: Chromatography and spectral analysis were respectively used to
      isolate and identify the constituents. RESULT: Seven compounds were isolated from
      the dried buds of L. confusa, and identified as rutin, quercetin, luteilin-7-O
      beta-D-galactoside, lonicerin, chlorogenic acid, beta-sitosterol and
      tetratriacontane. CONCLUSION: Rutin was isolated from the genus for the first
      time, and the others were isolated from the species for the first time.

PMID- 15575206
TI  - [Studies on dihydroflavonol glycosides from rhizome of Smilax glabra].
AB  - OBJECTIVE: To investigate the chemical constituents from the rhizomes of Smilax
      glabra. METHOD: The compounds were isolated by column chromatography with silica
      gel, Diaion HP-20 and ODS as packing materials, and HPLC. Their structures were
      determined on the basis of their spectral evidence. RESULT: 5 dihydro-flavonol
      glycosides were identified as: astilbin (1), neoastilbin (2), isoastilbin (3),
      neoisoastilbin (4), (2R, 3R)-taxifolin-3'-O-beta-D-pyranglucoside (5).
      CONCLUSION: Compounds 2, 4, 5 were isolated from this plant for the first time.

PMID- 15575207
TI  - [Determination of active anthraquinones in Rheum and its tea preparations by
      micellar electrokinetic capillary electrophoresis].
AB  - OBJECTIVE: To establish an instant determination method of emodin, aloe-emodin
      and rhein, from Rheum, and one of their preparations, Qinghai Wild Dahuang Tea,
      by micellar electrokinetic capillary electrophoresis for the first time. METHOD:
      Separation was carried out in an uncoated fused silica capillary (75 microm x
      50.0 cm). Meanwhile, a running voltage 20 kV, 15.0 mmol x L(-1) borax buffer with
      30.0 mmol x L(-1) SDS and 10% ethanol (pH 9.60) and a UV detector at 254 nm were
      adopted. RESULT: The linear calibration rang was 4-120 mg x L(-1) (r = 0.992 1)
      for emodin, 10-200 mg x L(-1) (r = 0.997 0) for aloe-emodin, and 2-100 mg x L(-1)
      (r = 0.997 1) for rhein, respectively. Under the optimum conditions, the relative
      standard deviation (RSD) values (n = 6) for the migration time and the peak area
      of each peak were 0.59%-0.80%, 1.30%-3.22%, respectively. The contents of the
      analytes were easily determined with recoveries ranging from 97.6%-102.3%.
      CONCLUSION: The method is proved to be simple, rapid and accurate, and can be
      used for the quality control of medicinal herb, Rheum, and its tea preparation.

PMID- 15575208
TI  - [Study on applying chromatographic fingerprints to establishing quality criterion
      of processed tuber of Pinellia pedatisecta].
AB  - OBJECTIVE: To explore the utility of principal component analysis (PCA) in
      conjunction with the window preprocessing scheme on chromatographic data for
      quality control. METHOD: Chromatographic fingerprints of processed tuber of
      Pinellia pedatisecta were determined by HPLC, and the Window Preprocessing and
      PCA were used for data processing. RESULT: The quantitative differences among
      different growing areas and different process batches were found with this
      method. CONCLUSION: The method can be used in quality control for monitoring
      between-batch products of traditional Chinese pharmaceutical process.

PMID- 15575209
TI  - [Study on serum proteome of rat endotoxemia treated by figwort root].
AB  - OBJECTIVE: To study the serum proteome of rat endotoxemia treated by figwort root
      (FR). METHOD: The differences of serum proteome among rats treated with
      lipopolysaccharide (LPS), FR, LPS + FR and saline respectively were analyzed by
      two-dimensional electrophoresis (2DE) assay. RESULT: The volumes of sixteen serum
      proteins (xPr) in LPS induced-endotoxemia group were greatly changed compared
      with those of the control group. Among them, the volumes of xPr 16, 19 were
      significantly decreased, and the volumes of xPr 1, 2, 3, 4, 5, 6, 7, 8, 9, 11,
      12, 14, 18, 23 were significantly increased. When treated with FR, the volumes of
      xPr 1, 6, 7, 8, 9, 11, 12, 14, 18, 23 were significantly decreased, and the
      volumes of xPr 8, 9, 11, 12, 23, 14 were back to normal level. Two factors
      statistic analysis showed that FR had interaction with LPS for xPr 1, 5, 8, 10,
      11, 12, 18, 19, 20, 21, 22, and FR might be the functional antagonist of LPS. We
      also observed that the volumes of xPr 10, 13, 15, 20, 21, 22 were found to change
      significantly only in FR treated group but not in LPS treated group or control
      group. Interestingly, the volume of xPr 13, 20, 21, 22 were increased and the
      volume of xPr 10, 15 were decreased. CONCLUSION: The molecular basis of
      therapeutic effect of FR on endotoxemia might be through the regulation of xPr 1,
      6, 7, 8, 9, 11, 12, 14, 18, 23. We can use proteomic techniques to study the
      molecular mechanisms of diseases treated by functional Chinese herbs and the
      combination of different herbs is necessary for the treatment of endotoxemia, as
      FR can not regulated all the changed proteins induced by LPS.

PMID- 15575210
TI  - [Experimental study on the antiviral mechanism of Ceratostigma willmattianum
      against herpes simplex virus type 1 in vitro].
AB  - OBJECTIVE: To study the antiviral effect and mechanisms of the liquid extract
      from Ceratostigma willmattianum against herpes simplex virus type 1 (HSV-1) in
      vitro. METHOD: C. willmattianum in various concentration was applied to different
      steps of HSV-1 replication cycle. 50% Tissue culture infective dose (TCID50),
      cytopathic effect (CPE), MTT staining method, dot blotting and Northern blotting
      analysis were used to estimate index of antiviral activity. RESULT: 50% Toxic
      concentration (TC50) was 1077 mg x L(-1), IC50 29.46 mg x L(-1) and therapeutic
      index (TI) 36.56 in C. willmattianum. TC50 330 mg x L(-1), 50% Inhibiting
      concentration (IC50) 9.12 mg x L(-1) and TI 36.18 in ACV by MTT staining method.
      The liquid extract from C. willmattianum had remarkable effect on inhibiting HSV
      1 in vitro. Ceratostigma could interfere absorption of HSV-1 to Vero cells to
      prevent HSV-1 infectivity, inhibit HSV-1 gD DNA replication and HSV-1 gD mRNA
      expression. CONCLUSION: C. willmattianum possesses strong anti-HSV-1 activity in
      vitro. The antiviral mechanisms are related to inhibiting virus absorption, HSV-1
      gD gene replication and HSV-1 gD gene transcription.

PMID- 15575211
TI  - [Study on the acute toxicity experiment of mice and anti-tumor function in vitro
      of the qinglongyi].
AB  - OBJECTIVE: To study the anti-tumor effect and acute toxicity in vitro of the
      separation compositions from qinglongyi. METHOD: The conventional acute toxicity
      experiments of mice, the MTT [3-(4,5-dimethylthiazol-2 yl)-2,5-diphenylterazolium
      bromide, MTT] and the SRB (sulforhodamin B) were used to make preliminary
      selection to qinglongyi and its separation compositions. RESULT: The half-deadly
      dose (LD50, the half-lethiferous dose) of the chloroform separation composition
      in qinglongyi was 575.38 mg x kg(-1) (i.g.), and of the acetic ether separation
      compositions in qinglongyi was 1303.59 mg x kg(-1) (i.g.). From the other parts
      of separation compositions in qinglongyi, the LD50 were more than 5 g x kg(-1).
      When acetic ether separation composition of qinglongyi was at 100 microg x mL(-1)
      the growth inhibitory rate (GIR) was < 50% to the leukaemia cell HL-60 of human.
      When chloroform separation composition and the acetic ether separation
      compositions of qinglongyi was at 100 mg x mL(-1), GIR was 52% to the leukaemia
      cell HL-60, the gastric carcinoma cell BGC-823 and the cervical carcinoma cell
      Hela of human. CONCLUSION: The separation composition of the chloroform and the
      acetic ether from qinglongyi have obvious, anti-tumor effect.

PMID- 15575212
TI  - [Effect of ginsenoside Rg1 on the influence of neprilysin expression induced by
      LPS in BT325 cell line].
AB  - OBJECTIVE: To investigate the effect of ginsenoside Rg1 on the influence of
      neprilysin expression induced by LPS in BT325 cell line. METHOD: MTT was used to
      measure the levels of the survival rate of BT325 cultured with ginsenoside Rg1
      and LPS in different concentrations. The expression of NEP was measured by RT
      PCR. RESULT: The survival rate of BT325 was obviously inhibited by LPS, and the
      expression of NEP was decreased. The survival rate of BT325 was obviously raised
      by ginsenoside Rg1, and the expression of NEP was increased. CONCLUSION: LPS can
      cause cell damage, and decrease the expression of NEP. Ginsenoside Rg1 can exert
      neuroprotective properties which protects BT325 cell line from the cell toxicity
      of LPS.

PMID- 15575213
TI  - [Effects of siwu tang on protein expression of bone marrow of blood deficiency
      mice induced by irradiation].
AB  - OBJECTIVE: To observe the effects of siwu tang on protein expression of bone
      marrow of blood deficiency mice and provide the theoretical and experimental
      basis for understanding the molecular mechanism of blood enriching function of
      siwu tang. METHOD: Blood deficiency mice were established by using 3.5 Gy 60Co
      gamma-ray. With proteomic technologies including two-dimensional electrophoresis,
      image analysis, in-gel digestion, peptide mass fingerprinting and bioinformatics
      the proteins of bone marrow of blood deficiency mice were isolated, analyzed, and
      identified. RESULT: Siwu tang could reverse 10 up-regulated and 4 down-regulated
      proteins of blood deficiency mice bone marrow. Seven of the proteins were likely
      to be lymphocyte specific protein 1, proteasome 26S ATPase subunit 4,
      hematopoietic cell protein-tyrosine phosphatase, glyceraldehyde-3-phosphate
      dehydrogenase, growth factor receptor binding protein 14 and lgals12
      respectively. CONCLUSION: Siwu tang can regulate the protein expression of bone
      marrow of blood deficiency mice and thus promote the growth and differentiation
      of hematopoietic cells and then exert its effects on blood enriching function.

PMID- 15575214
TI  - [Study on the compatibility of composite herbal medicines of the Zishen pill].
AB  - OBJECTIVE: To study the compatibility of composite herbal medicines of the Zishen
      pill. METHOD: 50% ethanol extract test solution of the different combinations of
      composite herbal medicines of the Zishen pill were prepared. Pharmacologic
      experiments, such as anti-inflammatory, carbon particle clearance of RES were
      carried out with the solutions, and the corresponding pharmacological data were
      obtained. Variance analysis, canonical correlation and stepwise regression
      analysis were applied to interrelate the amount of each drug and the
      pharmacological data. RESULT: The results confirmed that Huangbo and Zhimu were
      the basis, while Rougui was the corrigent, which was conformed to the theory of
      TCM. CONCLUSION: This study provides a significant try for studying the
      compatibility of composite herbal medicines.

PMID- 15575215
TI  - [Inhibitory effect of sinomenine on expression of cyclooxygenase-2 in
      lipopolysaccharide-induced PC-12 cells].
AB  - OBJECTIVE: To study the effects of sinomenine (Sin) on cell proliferation,
      intracellular expression of cyclooxygenase-2 (COX-2), and production of PGE2 in
      lipopolysaccharide-induced PC-12 cells, To explore the Sin's mechanism on nerve
      cell. METHOD: PC-12 cells were cultured with nerve growing factors (NGF), and
      pretreated with Sin at various concentrations (0, 3 x 10(-6), 30 x 10(-6), 150 x
      10(-6) mol x L(-1)) for 2 hours, then with or without stimulation of
      lipopolysaccharide (LPS). The proliferation activity of PC-12 cells was
      determined by 3H-TdR incorporation, and the production of PGE2 in culture
      supernatants of PC-12 cells was detected with competitive ELISA. Expression of
      COX-2 mRNA in PC-12 cells was analyzed by semi-quantitative RT-PCR, and
      expression of COX-2 protein was estimated by Western blot method and cellular
      enzyme immunoassay. Nuclear factor-kappa B (NF-kappaB) activity in whole-cell
      extract of PC-12 cells was also measured by an ELISA-based method. RESULT: The
      data showed that Sin down-regulated the expression of COX-2 mRNA and protein, and
      reduced the production of PGE2 in the LPS-stimulated PC-12 cells which correlated
      with Sin's concentrations positively. In addition, NF-kappaB activity in LPS
      stimulated cells was suppressed significantly by Sin. No inhibition of
      proliferation of PC-12 cells due to Sin treatment was observed. CONCLUSION: Sin
      mediates the down-regulation of expression of COX-2 and production of induced
      PGE2 in PC-12 cells by suppressing the activity of NF-kappaB.

PMID- 15575216
TI  - [Clinical study of modified M-VAC therapy with one 21-day cycle for advanced
      urothelial cancer].
AB  - Although M-VAC therapy is a standard chemotherapy for advanced transitional cell
      carcinoma, the treatment schedule has to be delayed or cancelled in many patients
      because of the toxicity. To reduce the toxicity we modified the treatment
      schedule of M-VAC treatment. The dosages of this simplified M-VAC therapy were 30
      mg/m2 methotrexate (on day 1), 3 mg/m2 vinblastine (on day 2), 30 mg/m2
      doxorubicin (on day 2) and 70 mg/m2 cisplatin (on day 2), with courses repeated
      every 21 days for four cycles as a principle. Seventeen patients with
      histologically proven advanced transitional cell carcinoma were treated with this
      simplified M-VAC therapy without dose modification or delay. The median number of
      cycles was 4. Neutropenia, anemia and thrombopenia (grade 4) was observed in 2, 1
      and 2 patients respectively, but no drug-related deaths were observed. Complete
      response and partial response were achieved in 2 (12%) and 10 (59%) patients
      respectively. Of 2 complete responders one patient was alive without evidence of
      disease at 12 months and another patient died of the disease at 42 months. Of 10
      partial responders 6 patients underwent the additional surgical resection of
      residual tumors. Of these 6 patients 3 patients are alive without evidence of
      disease at 6, 30 and 31 months. The remaining 3 developed recurrence and 2 died
      of the disease at 13 and 29 months. Five non-responders died of the disease at 5
      months after the start of the therapy. Response rate of simplified M-VAC therapy
      was excellent and treatment duration was short. However, relapses were commonly
      observed as well as the original M-VAC treatment.

PMID- 15575217
TI  - [A multi-center prospective study for antibiotic prophylaxis to prevent
      perioperative infections in urologic surgery].
AB  - In order to assess the ability of our protocol for antibiotic prophylaxis to
      prevent perioperative infections in urologic surgery, 1,353 operations of open
      and laparoscopic urologic surgery conducted in 21 hospitals between September
      2002 and August 2003 were subjected to analyses. We classified surgical
      procedures into four categories by invasiveness and contamination levels:
      Category A; clean less invasive surgery, Category B; clean invasive or clean
      contaminated surgery, Category C; surgery with urinary tract diversion using the
      intestine. Prophylactic antibiotics were administrated intravenously according to
      our protocol, such as Category A; first or second generation cephems or
      penicillins on the operative day only, Category B; first and second generation
      cephems or penicillins for 3 days, and Category C; first, second or third
      generation cephems or penicillins for 4 days. The wound conditions and general
      conditions were evaluated in terms of the surgical site infection (SSI) as well
      as remote infection (RI) up to postoperative day (POD) 30. The SSI rate highest
      (23.3%) for surgery with intestinal urinary diversion, followed by 10.0% for
      surgery for lower urinary tract, 8.9% for nephroureterctomy, and 6.0% for radical
      prostatectomy. The SSI rates in clean surgery including open and laparoscopic
      nephrectomy/adrenalectomy were 0.7 and 1.4%, respectively. In SSIs, gram-positive
      cocci such as methicillin-resistant Staphylococcus aureus (58.8%) or Enterobacter
      faecalis (26.5%) were the most common pathogen. Similarly, the RI rate was the
      highest (35.2%) for surgery using intestinal urinary diversion, followed by 16.7%
      for surgery for lower urinary tract, 11.4% for nephroureterctomy, and 7.6% for
      radical prostatectomy, while RI rates for clean surgery were less than 5%. RIs
      most frequently reported were urinary tract infections (2.6%) where Pseudomonas
      aeruginosa (20.3%) and Enterobacter faecalis (15.3%) were the major causative
      microorganisms. Parameters such as age, obesity, nutritional status (low
      proteinemia), diabetes mellitus, lung disease, duration of operation, and blood
      loss volume were recognized as risk factors for SSI or RI in several operative
      procedures. Postoperative body temperatures, peripheral white blood counts, C
      reactive protein (CRP) levels in POD 3 were much higher than those in POD 2 in
      cases suffering from perioperative infections, especially suggesting that CRP
      could be a predictable marker for perioperative infections.

PMID- 15575218
TI  - [Clinical experiences of endotoxin removal in urinary obstruction: report of two
      cases].
AB  - Clinical experiences of endotoxin removal using polymyxin B immobilized fiber
      column (PMX) in two septic shock patients are reported. Case 1: A 74-year-old man
      with bladder cancer received a total cystectomy and a ileal conduit 19 years
      before he was referred to our hospital with complaints of high fever and general
      fatigue. Physical examination and laboratory data revealed severe hypotension,
      and pyuria. Left hydronephrosis due to uretero-intestinal stenosis were observed
      on computed tompgraphy (CT). Under the diagnosis of septic shock, left
      nephrostomy were performed. Direct hemoperfusion using polymyxin B immobilized
      fiber column was carried out. Case 2: A 74-year-old woman referred to our
      hospital with complaints of abdominal pain. Physical examination and laboratory
      data revealed severe hypotension, and pyuria. Right hydronephrosis due to
      retroperitoneal fibrosis were observed on CT. Diagnoses of septic shock were
      made. After right nephrostomy were performed, direct hemoperfusion using
      polymyxinB immobilized fiber column was carried out.

PMID- 15575219
TI  - [Adrenocorticotropic hormone-secreting adrenal pheochromocytoma: a case report].
AB  - A 55-year-old woman with transient faintness was referred to our hospital.
      Laboratory studies showed high levels of plasma catecholamines, cortisol,
      adrenocorticotropic hormone (ACTH) and urinary vanyl mandelic acid (VMA).
      Abdominal computed tomography (CT) showed a right adrenal tumor measuring 4.5 cm
      diameter that was enhanced heterogeneously by contrast medium. Brain CT and chest
      CT did not detect any other tumors. Under the clinical diagnosis of ectopic ACTH
      secreting adrenal pheochromocytoma, we performed right adrenalectomy.
      Pathological findings showed pheochromocytoma, and tumor cells were
      heterogeneously stained by anti-ACTH antibody.

PMID- 15575220
TI  - [Ruptured renal angiomyolipoma treated by transcatheter arterial embolization:
      report of two cases].
AB  - We report two cases of spontaneous rupture of renal angiomyolipoma (AML). In the
      first case, a 22-year-old woman was admitted with lower abdominal pain. She was
      diagnosed with rupture of left renal AML. Transcatheter arterial embolization
      (TAE) was performed for three times to preserve renal function, and the size of
      AML decreased to 6.5 cm from 10 cm. In the second case (74-year-old woman), the
      chief complaint was lower abdominal pain. The clinical diagnosis of this patient
      was rupture of right renal AML. The size of this AML markedly reduced due to TAE.
      TAE is an effective therapy for rupture of renal AML.

PMID- 15575221
TI  - [A case of Bellini duct carcinoma with giant hydronephrosis].
AB  - We report a case of Bellini duct carcinoma with giant hydronephrosis. A 56-year
      old man was referred with the chief complaint of gross hematuria. The intravenous
      pyelography showed a huge right renal contour and non-functioning kidney. The
      abdominal computed tomographic scan and magnetic resonance imaging demonstrated
      giant hydronephrosis. Percutaneous urinary cytology obtained in the direct
      pyelography was class V. Right total nephro-ureterectomy was performed. Punctured
      fluid volume was 1,010 ml during the operation. Histological and
      immunohistochemical analysis revealed the collecting duct carcinoma of the
      kidney. Three months later, multiple bone metastases had appeared. He was treated
      by the combination chemotherapy of gemcitabine and paclitaxel, but lung and liver
      metastases developed. The patient died of cancer 12 months later. This case was
      considered to be Bellini's duct carcinoma as its features had poor prognosis and
      image findings infiltrating from medulla to cortex with the total enlargement of
      the kidney. To our knowledge there has been no case found like these atypical
      imaging findings.

PMID- 15575222
TI  - [Vesicovaginal fistula which arose postoperatively after removal of the ureter by
      the intussusception method for renal pelvic tumor: a case report].
AB  - A 64-year-old woman underwent right nephroureterectomy of the ureter by the
      intussusception method under the diagnosis of right renal pelvic tumor in
      December 2001. Stress incontinence appeared postoperatively, and though
      conservative treatment was performed, it did not improve. The result of the pad
      weighting test was 56 g indicating serious incontinence. In chain cystography,
      contrast media from the posterior wall of the urinary bladder to the vagina
      leaked out by the lateral view, and in cystoscopy, a fistula of about 2 mm in
      diameter was recognized in the right ureteral orifice trace. Under the diagnosis
      of vesicovaginal fistula, we performed transvaginal repair of the vesicovaginal
      fistula in November 2003. The urethral catheter was removed on the 14th
      postoperative day. After removal of the urethral catheter, urge incontinence was
      recognized, but it improved gradually. The recurrence of fistula and tumor has
      not been recognized at present.

PMID- 15575223
TI  - [A case of urachal actinomycosis with bone formation].
AB  - We report a case of urachal actinomycosis with bone formation. A 76-year-old
      woman was admitted to our hospital with a complaint of gross hematuria.
      Cystoscopy revealed bleeding from the dome of the bladder wall. Magnetic
      resonance imaging revealed a mass extending from the dome of the bladder to just
      below the umbilicus. A urachal tumor was clinically suspected, and the mass was
      resected together with urachal remnant and part of the bladder wall. Pathological
      diagnosis of the specimen was actinomycosis. The bone tissue was found in the
      abcess. Actinomycosis is a chronic suppurative infection caused by Actinomyces
      israelii. Although urachal actinomycosis is a rare desease, it is important to
      recognize this uncommon intrapelvic infection as the differential diagnosis of
      any intrapelvic mass.

PMID- 15575224
TI  - [Urachal carcinoma treated with neoadjuvant intra-arterial chemotherapy: a case
      report].
AB  - A 43-year-old man visited our clinic with gross hematuria. Ultrasonography and
      computed tomography demonstrated a tumor at the bladder dome. Cold punch biopsy
      revealed well-differentiated adenocarcinoma and stage III A urachal carcinoma was
      diagnosed. Neoadjuvant intra-arterial chemotherapy with cisplatin, adriamycin and
      angiotensin II was performed and 40% reduction of tumor size was noted 3 weeks
      after this therapy. En bloc segmental resection was performed. Augmentation
      ilealcystoplasty was subsequently performed to secure bladder capacity. Adjuvant
      chemotherapy (UFT) was given for 1 year. Cystolithotomy and closure of ventral
      hernia were required 10 years after radical surgery for postoperative
      complications. The patient has survived 12 years with no evidence of local
      recurrence or distant metastasis.

PMID- 15575225
TI  - [A case of retroperitoneal abscess by anaerobic bacteria].
AB  - A case of retroperitoneal abscess with an unknown origin is presented. A 60-year
      old woman visited our hospital complaining of fever and right flank pain.
      Abdominal computed tomography and ultrasound examination revealed retroperitoneal
      abscess posterior to right kidney. Percutaneous drainage and administration of
      antibiotics were performed. Then, both symptoms were improved. The fluid culture
      proved to be anaerobic bacteria, Peptostreptococcus species and Porphyromonas
      asaccharolytica. She had no history of surgery or diabetes mellitus. The origin
      of this abscess was unknown.

PMID- 15575226
TI  - [Primary malignant lymphoma of the ureter: a case report].
AB  - A 58-year-old man who had right hydronephrosis pointed out by medical checkup
      visited our hospital. Computed tomography and retrograde pyelography revealed a
      soft tissue mass in the middle portion of the right ureter. Urine cytology
      specimen from the right ureter suggested transitional cell carcinoma. Under the
      diagnosis of right ureteral cancer, we performed right total nephro-ureterectomy,
      partial cystectomy. The histopathological examination showed non-Hodgkin lymphoma
      (large B-cell type) of the ureter. Our diagnosis was Clinical Stage IE of the Ann
      Arbor Classification. The patient received only the first course of systemic
      chemotherapy (THP-cop), because he suffered severe thrombocytopenia in the course
      of the chemotherapy. No recurrence was found for 15 months after operation, and
      at present he is disease-free.

PMID- 15575227
TI  - [Metastatic intrapelvic tumor from esophageal cancer: a case report].
AB  - We report a case of a metastatic intrapelvic tumor arising from esophageal
      cancer. The patient, a 74-year-old man, visited our hospital with the chief
      complaint of gross hematuria. Magnetic resonance imaging and cystoscopy revealed
      a huge intrapelvic tumor which invaded the bladder, rectum, sigmoid colon and
      left ilium. The patient underwent total pelvic evisceration with ileal conduit
      and colostomy. Pathologic diagnosis of the intrapelvic tumor was moderately
      differentiated squamous cell carcinoma. Preoperatively, gastrointestinal
      fiberscopy revealed an esophageal tumor, and biopsy showed moderately
      differentiated squamous cell carcinoma. Finally, the intrapelvic tumor was
      diagnosed as metastatic tumor from esophageal cancer.

PMID- 15575228
TI  - Reconstruction of posterior urethral disruption: tips for success from our
      experience and from a literature review.
AB  - Repair of a posterior urethral disruption associated with a pelvic fracture is a
      challenge for urologic surgeons. Here, we provide surgical and strategic tips to
      facilitate the delayed surgical repair of urethral distraction defects. Nine
      patients each with a traumatic posterior urethral distraction defect underwent
      delayed transperineal or transperineoabdominal bulboprostatic anastomosis. Four
      patients had previously undergone multiple procedures. Seven patients regained
      satisfactory urination without incontinence, although one other patient is
      suffering from incontinence. In one patient, urethral disruption occurred again
      after removal of the urethral catheter, and he is being managed by suprapubic
      catheter. In our experience, the key to success is to perform a true
      bulboprostatic mucosa-to-mucosa anastomosis without tension. For this purpose, a
      transperineoabdominal approach is of particular importance when the healthy
      mucosa of the prostatic apex cannot be revealed through a perineal approach due
      to dense fibrous scar or fractured bone. A partial pubectomy may be necessary
      according to the situation. By the transperineoabdominal approach, the scar
      tissue can be bypassed through a broad sub-pubic-arch tunnel, and a reliable
      anastomosis achieved.

PMID- 15575229
TI  - [Recurrent epididymitis in a boy with a webbed penis without chordee: a case
      report].
AB  - An 11-year-old boy visited our clinic complaining of recurrent epididymitis for 2
      years. No abnormal findings were found in urine and blood sampling tests,
      ultrasonography of the urinary tracts or in a pelvic magnetic resonance imaging
      examination. Induration of the left epididymal tail, webbed penis and true
      phimosis were observed. Neither hypospadias nor chordee were identified, thus the
      diagnosis of "webbed penis without chordee" was made. The operation for webbed
      penis by transverse incision followed by longitudinal suture and dorsal incision
      for true phimosis was performed successfully. The postoperative course was
      uneventful and no recurrence of epididymitis has occurred.

PMID- 15575230
TI  - [Testicular abscess: report of 2 cases].
AB  - We report two cases of testicular abscess. The first case is in a 53-year-old man
      who had been suffering from diabetes mellitus. Because of cerebral infarction, he
      had been bedridden and a Foley catheter had been indwelt for a long period of
      time. The second case is in a 78-year-old man who had suffered from acute
      prostatitis six months earlier. In both cases, the chief complaints were high
      fever and painful scrotal swelling. At initial evaluation, ultrasonography
      revealed that the affected testes were swollen without abscess formation and an
      ipsilateral epididymal swelling was demonstrated in the second case but not in
      the first case. The urine bacterial culture (UBC) result was positive for
      Escherichia coli in first case and Pseudomonas aeruginosa in the second case. In
      both cases, fever and scrotal pain subsided after antibiotic chemotherapy, and
      inflammatory reactions on routine blood studies were normalized within 2 weeks.
      Nevertheless, the swollen testes did not sigunificantly reduce in size, and
      testicular abscess was suspected by magnetic resonance imaging (MRI). Orchiectomy
      was performed, and intratesticular abscess formations were confirmed
      macroscopically and microscopically. In each case, bacterial culture from the
      abscess was positive for the same bacterium as detected from the UBC. It is
      difficult to distinguish testicular abscess from acute epididymitis at the early
      stage because of similarities on symptoms or signs between the two. If testicular
      swelling lasts after appropriate chemotherapy, we believe that attention should
      be directed to testicular abscess, which needs orchiectomy to obtain a complete
      cure and MRI is useful in its diagnosis.

PMID- 15575231
TI  - Regression of liver fibrosis in patients treated by interferon.

PMID- 15575232
TI  - Seronegative alpha-fetoprotein-producing gastric cancer: an early form of
      aggressive cancer.

PMID- 15575233
TI  - Inhibition of type-5 phosphodiesterase: promising therapy for pulmonary
      hypertension.

PMID- 15575234
TI  - Sarcoidosis of the hypothalamus and pituitary.

PMID- 15575235
TI  - Uncommon association of hypersensitivity pneumonitis by Aspergillus and pulmonary
      aspergilloma; a new clinical entity?

PMID- 15575236
TI  - Transformation of low-grade B-cell tumor to large cell lymphoma.

PMID- 15575237
TI  - Reversible posterior leukoencephalopathy syndrome.

PMID- 15575238
TI  - Regression of liver fibrosis in cases of chronic liver disease type C:
      quantitative evaluation by using computed image analysis.
AB  - OBJECT: It was reported that the liver fibrosis is reduced in patients with
      chronic liver disease type C after eradication of HCV. Degree of fibrosis was
      expressed by the classical fibrosis scoring system (F0-F4) at present. However a
      change of subtle reduction of fibrosis cannot be expressed in its fibrosis score
      and thus we measured an area of fibrosis and compared detailed change of the
      fibrosis area in paired liver biopsy. METHODS: For quantitative assessment of
      liver fibrosis, we measured an area of fibrosis using computed digital image
      analysis and pursued the rate of a fibrosis area for whole biopsied liver tissue
      of 25 patients with HCV infection (20 complete response patients to IFN therapy
      who showed viral eradication: CR and 5 non-treated ones with IFN but had
      conservative therapy: CT). RESULTS: In CR group, fibrosis rate was 7.2 +/- 1.5%
      before therapy, 2.7 +/- 0.5% after the therapy and they were significantly
      regressed. In CT group, fibrosis rate was 8.4 +/- 4.3% at the first biopsy, 15.9
      +/- 7.7% at the second biopsy. CONCLUSIONS: Regression of liver fibrosis could be
      confirmed in patients with virologic response to IFN even in patients with liver
      cirrhosis. Our quantitative evaluation provided information superior to that
      obtained by the classical fibrosis staging score system.

PMID- 15575239
TI  - Increased cardiac mortality in women compared with men in patients with acute
      myocardial infarction.
AB  - OBJECTIVE: It has been reported that women with acute myocardial infarction (AMI)
      have a higher short-term mortality rate than men, but the reason is not known.
      The profile in relation to age, gender and risk factors was evaluated to compare
      AMI and unstable angina pectoris (UAP). METHODS: Findings from 984 patients
      including 580 patients with AMI (129 women, 451 men) and 404 patients with UAP
      (131 women, 273 men) were analyzed by the South Osaka Acute Coronary Syndrome
      Study Group (SACS). The primary endpoint of the study was in-hospital death. The
      primary endpoints of interest (cardiac death) were fatal recurrent myocardial
      infarction, death from congestive heart failure, and sudden death. RESULTS:
      Cardiac death during hospitalization within 30 days in AMI was higher in women
      than in men (12.4% vs 6.7%, p < 0.05). On the other hand, in UAP there was no
      significant difference between women and men (1.5% vs 0.7%, NS). The incidence of
      cardiac death in AMI was significantly higher for patients 75 years old and older
      (19.0%) than for patients less than 55 years old (4.2%), 55-64 years old (3.5%)
      and 65-74 years old (4.7%) (p < 0.001, respectively). CONCLUSIONS: Cardiac death
      was higher for women compared with men in patients with AMI. The worse prognosis
      for the AMI women patients was likely to be derived from less performance of
      percutaneous coronary intervention, and a high incidence of severe myocardial
      infarction. Further research should be focused on the analysis of various
      clinical backgrounds.

PMID- 15575240
TI  - Association between serum C-reactive protein levels and microalbuminuria: a
      population-based cross-sectional study in northern Iwate, Japan.
AB  - OBJECTIVE: The presence of microalbuminuria is a renal marker of vascular
      endothelial damage, and is an independent and strong predictor of increased risk
      for cardiovascular mortality and morbidity. Elevated circulating C-reactive
      protein (CRP) levels have recently been reported to be a novel cardiovascular
      risk factor, and it has been suggested that this acute-phase protein impairs
      vascular endothelial function. The aim of the present study was to determine
      whether serum CRP level is a dependent or an independent risk factor of
      microalbuminuria in the general population. METHODS: Subjects of this cross
      sectional study were apparently healthy individuals drawn from the general
      Japanese population (mean age, 62; men, 2,236; women, 4,217). Serum CRP levels
      were determined using a highly sensitive kit and urine albumin-creatinine ratio
      (UACR) was calculated using a single urine sample. Multivariate logistic
      regression analysis was used to determine which risk factors (ie, age,
      hypertension, diabetes, obesity, hypercholesterolemia, smoking, and CRP) might
      predict the presence of microalbuminuria. RESULTS: In addition to classical
      cardiovascular risk factors such as age, hypertension, diabetes and obesity,
      serum CRP levels are also significantly correlated with microalbuminuria in men
      (odds ratio = 1.42, 95% CI = 1.13-1.79; p < 0.01) and women (odds ratio = 1.25,
      95% CI = 1.05-1.49; p < 0.01). When subjects with diabetes were excluded from the
      analysis, serum CRP levels continued to be a significant predictor for
      microalbuminuria (odds ratio = 1.35, 95% CI = 1.06-1.73; p < 0.05 for men: odds
      ratio = 1.23, 95% CI = 1.03-1.47; p < 0.05 for women). CONCLUSIONS: The present
      study has shown that low-grade inflammation as represented by high sensitivity
      CRP levels may be significantly related to the presence of microalbuminuria. This
      suggests that microalbuminuria may be a useful marker representing systemic low
      grade inflammation as well as being an established cardiovascular risk factor in
      apparently healthy individuals.

PMID- 15575241
TI  - Seronegative alpha-fetoprotein-producing early gastric cancer treated with
      endoscopic mucosal resection and additional surgery.
AB  - A 67-year-old man visited our hospital for the treatment of gastric carcinoma.
      Endoscopic mucosal resection was performed, however, histological examination of
      the resected specimen revealed tumor invasion to the submucosal layer with vessel
      invasion. Immunohistological studies were carried out on resected specimens and
      part of the cancerous lesion showed a positive reaction for alpha-fetoprotein
      (AFP), but the serum AFP level was normal. Additional distal gastrectomy with
      lymph node dissection revealed lymph node metastasis although there was no
      apparent finding of lymph node swelling by preoperative diagnostic imaging. This
      patient remains alive without disease for 3 years after surgery.

PMID- 15575242
TI  - Renal transplant recipient with chronic hepatitis C who obtained sustained viral
      response after interferon-beta therapy.
AB  - A 44-year-old Japanese woman with a history of living-related renal
      transplantation was treated with interferon-beta (IFN-beta) for chronic infection
      with sero-group 2 hepatitis C virus (HCV). Serum HCV-RNA titer was 160 kilo
      international units/ml. Treatment with intravenous IFN-beta daily was given for 6
      weeks. Serum HCV-RNA was undetectable at 3 weeks after initiating therapy. Renal
      graft rejection did not occur. Six months after completing therapy, she obtained
      sustained viral response. This case demonstrates that IFN-beta therapy safely
      induced clearance of HCV in a renal transplant recipient with stable renal
      function, low viral load and/or HCV sero-group 2.

PMID- 15575243
TI  - Intravascular hemolysis in aortic stenosis.
AB  - A 67-year-old woman with rheumatic aortic stenosis for 20 years was admitted to
      our hospital. Although she had no overt symptoms, she had severe aortic valve
      stenosis with a transvalvular pressure gradient of more than 150 mmHg. She had
      also been suffering from anemia and mild chronic renal failure. A peripheral
      blood smear showed numerous fragmented erythrocytes. Hemoglobin was 8.4 g/dl,
      lactate dehydrogenase was 316 IU/l, haptoglobin was less than 7.3 mg/dl, and
      hemosiderinuria was evident. We diagnosed intravascular hemolysis related to
      aortic stenosis. After we performed an aortic valve replacement, fragmentation on
      the peripheral blood smear dramatically disappeared.

PMID- 15575244
TI  - Late onset of Wolff-Parkinson-White syndrome in a 72-year-old man.
AB  - We encountered a case of wide QRS tachycardia with chronic atrial fibrillation in
      Wolff-Parkinson-White syndrome. Unique features were late onset of syncope
      attacks associated with this tachycardia at an advanced age of 72 years old
      without previous documentation of Wolff-Parkinson-White syndrome on
      electrocardiogram. He had a high likelihood of sudden cardiac death. Catheter
      ablation using CARTO system easily led to a successful ablation of the accessory
      pathway. The mechanism of late onset of the wide QRS tachycardia was attributed
      to possible changes of electrophysiologic properties including the atrio
      ventricular node and/or the accessory pathway, and the unique location of the
      accessory pathway.

PMID- 15575245
TI  - Marked improvement with sildenafil in a patient with primary pulmonary
      hypertension unresponsive to epoprostenol.
AB  - We report a 48-year-old woman with right heart failure due to primary pulmonary
      hypertension. Continuous infusion of epoprostenol (prostaglandin I2) for 1.5
      years failed to control her condition, but she was later successfully treated
      with additional sildenafil for a few months. Her mean pulmonary artery pressure
      was originally 57 mmHg, increased to 62 mmHg with epoprostenol, and decreased to
      45 mmHg with sildenafil. Additional sildenafil may be an effective and life
      saving agent in patients with primary pulmonary hypertension who show a poor
      response to epoprostenol, which is considered to be very powerful medical
      treatment for the disease.

PMID- 15575246
TI  - Dilated cardiomyopathy in Kugelberg-Welander disease: coexisting sleep disordered
      breathing and its treatment with continuous positive airway pressure.
AB  - A rare complication of possible secondary dilated cardiomyopathy to Kugelberg
      Welander disease was described in a 53-year-old patient with this inherent motor
      neuron disease, whom we diagnosed after a genetic analysis of the defective
      survival motor neuron gene. An association of sleep disordered breathing of
      Cheyne-Stokes respiration was diagnosed, which was virtually eliminated with
      continuous positive airway pressure via nasal mask. Considering the paucity of
      therapeutic options in most degenerative neuromuscular disorders, ameliorations
      in not only sleep quality but also cardiac function with continuous positive
      airway pressure have clinical implications.

PMID- 15575247
TI  - Alcoholic ketoacidosis associated with multiple complications: report of 3 cases.
AB  - We report 3 patients with alcoholic ketoacidosis (AKA). All had a history of
      excessive intake and abrupt termination of alcohol. They showed tachypnea,
      tachycardia, abdominal tenderness, and epigastralgia. Metabolic acidosis with an
      increased anion gap, decreased PaCO2 and ketonemia were present. One patient
      whose ratio of 3-hydroxybutyric acid to acetoacetic acid was 4.0 was associated
      with diabetic ketoacidosis. All patients were successfully hydrated with
      electrolyte, glucose and thiamine. Complications such as liver dysfunction,
      lactic acidosis, acute pancreatitis, Wernicke's encephalopathy, rhabdomyolysis
      and heart failure were present. Attention should be paid to multiple
      complications in the treatment of AKA.

PMID- 15575248
TI  - Diabetes insipidus from neurosarcoidosis: long-term follow-up for more than eight
      years.
AB  - Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome
      including diabetes insipidus (DI) were followed up for more than 8 years from the
      onset of clinical manifestation. The mean age was 26 years, male : female ratio
      was 3 : 1 and the mean disease duration of 10 years. All patients had
      hypogonadism, hyperprolactinemia. Pituitary enlargement with thickening of the
      pituitary stalk were detected by magnetic resonance imaging (MRI) with gadolinium
      enhancement and attenuation in the intensity of the posterior lobe of the
      pituitary was detected without enhancement. Corticosteroid therapy resulted in
      the initial improvement of symptoms and gradual decrease in the tumor size but
      failed to cure polyuria due to DI. The use of desmopressin was necessary for a
      long period. None of these patients died from DI or central neurosarcoidosis.

PMID- 15575249
TI  - High molecular weight form insulin-like growth factor II-producing mesenteric
      sarcoma causing hypoglycemia.
AB  - An 81-year-old woman presented with frequent episodes of hypoglycemia. Her serum
      level of insulin was normal, but her serum insulin-like growth factor (IGF)-II
      level was high. She was found to have a spindle cell sarcoma originated from the
      mesentery of the sigmoid colon, which was completely resected. Postoperatively,
      hypoglycemia ameliorated with concomitant reduction in serum IGF-II levels.
      Immunohistochemical study revealed positive immunostaining for IGF-II in tumor
      cells, and the abundant expression of IGF-II mRNA was demonstrated by RT-PCR. The
      presence of high molecular weight (HMW) form IGF-II in patient's serum was
      confirmed by immunoblotting. This is the first report of a patient with HMW form
      IGF-II-producing mesenteric sarcoma causing hypoglycemia.

PMID- 15575250
TI  - Diagnostic usefulness of bronchoalveolar lavage in Hermansky-Pudlak syndrome: a
      case with double lung cancers.
AB  - A 65-year-old man was admitted to our hospital because of dyspnea on exertion. He
      had oculocutaneous albinism innately and his parents were consanguineous. His
      chest roentgenogram on admission showed reticulo-nodular infiltrates and cystic
      changes throughout both lung fields, and 7 cm mass in the left middle field.
      Cytology of bronchoalveolar lavage fluid (BALF) revealed macrophages containing
      ceroid. The diagnosis of HPS was made clinically and the tumor was diagnosed as
      poorly differentiated adenocarcinoma of the lung. He died of respiratory failure.
      By autopsy, additional well-differentiated adenocarcinoma was detected. Cytology
      of BALF was useful to confirm ceroid accumulation in the lung.

PMID- 15575251
TI  - Pleural cryptococcosis with idiopathic CD4 positive T-lymphocytopenia.
AB  - A 19-year-old man was admitted to our hospital because of chest pain. He was
      diagnosed as having pleural cryptococcosis by pleural biopsy. His CD4 positive T
      lymphocyte count was low (< 300 microl) and there was no evidence of human
      immunodeficiency virus infection. He was successfully treated with fluconazole.
      However, his CD4 positive lymphocyte counts remained low after the recovery and
      he was diagnosed as idiopathic CD4 positive T-lymphocytopenia. Pleural
      cryptococcosis is rare and its predisposing condition is still controversial. To
      our knowledge, this is the first case of pleural cryptococcosis associated with
      idiopathic CD4 positive T lymphocytopenia.

PMID- 15575252
TI  - Chronic hypersensitivity pneumonitis caused by Aspergillus complicated with
      pulmonary aspergilloma.
AB  - A 57-year-old man consulted our hospital with a history of the gradual onset of
      dyspnea and a productive cough. Chest computed tomographic (CT) scans showed a
      nodular shadow in a cavity lesion, and reticulonodular, cystic, and ground-grass
      opacities in the bilateral lung fields with honeycombing. He was diagnosed as
      having pulmonary aspergilloma and idiopathic pulmonary fibrosis (IPF). As an
      outpatient, he suffered from dyspnea upon physical exertion with exacerbation of
      the high-resolution CT (HRCT) opacities. An inhalation provocation test for
      Aspergillosis fumigatus was positive and chronic hypersensitivity pneumonitis
      (CHP) caused by Aspergillus was finally diagnosed. Insidious CHP is sometimes
      misdiagnosed as IPF. The diagnosis of insidious CHP should be made on the basis
      of a detailed history, specific HRCT findings, and lymphocyte-dominant
      bronchoalveolar lavage fluid cell findings.

PMID- 15575253
TI  - Unusual skin reactions after mosquito bites and Epstein-Barr virus reactivation
      in a patient with mantle cell lymphoma.
AB  - We detected Epstein-Barr virus (EBV) reactivation in a patient with mantle cell
      lymphoma (MCL). The patient, a 53-year-old Japanese man, had been referred to our
      hospital because of generalized lymphadenopathy, hepatosplenomegaly and
      lymphocytosis and gave a history of intense skin reactions to mosquito bites. The
      biopsied lymph node contained a monotonous proliferation of medium-sized
      lymphocytes with scant cytoplasm and slightly irregular nuclei that were CD5+,
      CD20+ and CD23-. Antibody titers of IgG against EBV viral capsid antigen and
      early antigen were increased, and EBV was detected in the lymphoma cells. This
      case may suggest a relationship between EBV and MCL.

PMID- 15575254
TI  - Multiple brain tumors of diffuse large B cell lymphoma in a patient with
      Waldenstrom's macroglobulinemia/ lymphoplasmacytic lymphoma: PCR and DNA sequence
      analysis show evidence of differences in clonality of the two B cell
      malignancies.
AB  - Multiple brain tumors of diffuse large B cell lymphoma (DLBL) were observed in a
      75-year-old man with Waldenstrom's macroglobulinemia (WM). Paravertebral and
      multiple subcutaneous nodules occurred in succession and he died 4 months after
      onset. We investigated B cell monoclonality by means of polymerase chain reaction
      (PCR) analysis and sequencing of the immunoglobulin heavy chain of paraffin
      embedded sections. The PCR product of the brain tumors showed a different
      rearrangement pattern from those of the other sections. The co-occurrence of DLBL
      with WM is rare, and some investigators have examined the clonality of the two
      malignancies. This case is important because DLBL brain tumors co-occurred with
      WM, enabling us to prove that DLBL and WM have different clonality.

PMID- 15575255
TI  - Subacute bulbar palsy as the initial sign of follicular thyroid cancer.
AB  - We report a 64-year-old woman with follicular thyroid cancer found by subacute
      bulbar palsy. Progressive bulbar palsy (PBP) was considered the most likely
      diagnosis, because no abnormal finding was detected on brain CT and blood test
      except for the decrease of free T4. An echogram of the thyroid revealed a small
      nodule which was shown to be class IIb by fine needle biopsy. However, 201Tl
      scintillation examination showed skull base metastasis. Follicular thyroid cancer
      sometimes seems to manifest as a distant metastasis with no clinically evident
      thyroid lesion. This case suggested the importance of a detailed survey for
      malignancy, when subacute bulbar palsy is seen.

PMID- 15575256
TI  - A woman with infectious endocarditis caused by Abiotrophia defectiva.
AB  - A 74-year-old woman with recurrent fever and multiple joint pain was admitted to
      Hokkaido University Hospital. Trans-esophageal echocardiogram revealed bacterial
      vegetation and destruction of the aortic valve. Although few bacteria grew in
      regular blood agar, Gram-positive coccobacillus was specifically grown in
      chocolate blood agar and Brucella agar, and it was identified to be Abiotrophia
      defectiva. Infectious endocarditis caused by Abiotrophia defectiva was diagnosed,
      she was treated with diuretics, penicillin G and gentamicin, and she immediately
      improved. Infectious diseases caused by Abiotrophia defectiva are extremely rare,
      and identification of this pathogen is important, as its bacterial
      characteristics require proper attention.

PMID- 15575257
TI  - Hodgkin's disease-related central nervous system angiopathy presenting as
      reversible posterior leukoencephalopathy.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical syndrome
      characterized by headache, conscious disturbance, seizure, and cortical visual
      loss with neuroimaging finding of edema in the posterior regions of the brain,
      with a reversible course (1). The precise pathomechanism of RPLS is not
      understood. However, association with uncontrolled hypertension, renal failure,
      eclampsia, or immunosuppressive agents has been implicated (1). We describe
      herein a case of Hodgkin's disease (HD)-related central nervous system (CNS)
      angiitis with neuroimaging finding suggestive of RPLS. The pathophysiology of
      RPLS in cases with CNS angiitis is discussed.

PMID- 15575258
TI  - Swollen nail folds due to leukemic cell infiltration in a case of chronic
      lymphocytic leukemia.

PMID- 15575259
TI  - 5-FU-induced acute leukoencephalopathy.

PMID- 15575260
TI  - Fish transport toxins hundreds of miles.

PMID- 15575261
TI  - Positive feedbacks shaping climate-change forecasts.

PMID- 15575262
TI  - The challenges of sustainable papermaking.

PMID- 15575263
TI  - Effect of application variables on emissions and distribution of fumigants
      applied via subsurface drip irrigation.
AB  - Soil fumigation is useful for controlling soil-borne pests and diseases in high
      cash-value crops. Fumigants are highly volatile, and approaches to reduce
      atmospheric emissions are required to protect human and environmental health.
      Application of fumigants through drip irrigation has been proposed as a means to
      decrease fumigant emissions, improve fumigant distribution in soil, and minimize
      worker exposure. These experiments were conducted to investigate the effect of
      the configuration of the drip system on the volatilization and distribution of
      the fumigants 1,3-dichloropropene (1,3-D), propargyl bromide (PrBr), and methyl
      isothiocyanate (MITC) in bedded systems. Results indicated that changing the drip
      emitter spacing and using multiple drip lines in each bed had little effect on
      the emissions and distribution of any fumigant. Increasing the depth of
      application from 15 to 30 cm reduced volatilization of MITC by approximately 20
      to >90%; emissions were reduced due to a decrease in the flux from the bed top,
      and deeper injection did not change the amount of fumigant volatilized from the
      bed side slope and furrow. Increasing the application depth resulted in a slight
      decrease in the rate of fumigant dissipation in soil, indicating the potential
      for some improvement in pest-control efficacy with deeper application.

PMID- 15575264
TI  - Distribution and fate of HBCD and TBBPA brominated flame retardants in North Sea
      estuaries and aquatic food webs.
AB  - Tetrabromobisphenol A (TBBPA) and hexabromocyclododecane diastereoisomers (alpha
      , beta/-, and gamma-HBCD) were investigated in effluents from sewage treatment
      works, landfill leachates, sediments, and food web organisms of the North Sea
      basin. Residues were quantified by liquid chromatography-mass spectrometry. Both
      flame retardants were enriched in sewage sludges, where a maximum total (sigma)
      HBCD concentration of 9.1 mg/kg (dry weight; d.w.) was found; TBBPA was at levels
      of 102 microg/kg. Landfill leachates from The Netherlands showed up to 36 mg
      (sigmaHBCD)/ kg (d.w.). gamma-HBCD dominated isomeric profiles in sediments, and
      concentrations were elevated near to a site of HBCD manufacture. alpha-HBCD was
      the primary congener detected in marine mammals; however, very few samples
      exhibited TBBPA. sigmaHBCD ranged from 2.1 to 6.8 mg/kg (lipid weight; l.w.) in
      liver and blubber of harbor porpoises (Phocoena phocoena) and seals (Phoca
      vitulina). TBBPA levels in cormorant (Phalacrocorax carbo) livers were up to 1
      order of magnitude lower compared to sigmaHBCD. HBCD in eels (Anguilla anguilla)
      from the Scheldt basin (Belgium) reflected the spatial distribution of
      concentrations in local sediments. This study shows evidence of HBCD
      bioaccumulation at the trophic level and biomagnification in the ascending
      aquatic food chain, and these findings justify risk assessment studies at the
      ecosystem level.

PMID- 15575265
TI  - Atmospheric dry deposition of persistent organic pollutants to the Atlantic and
      inferences for the global oceans.
AB  - Atmospheric deposition to the oceans is a key process affecting the global
      dynamics and sinks of persistent organic pollutants (POPs). A new methodology
      that combines aerosol remote sensing measurements with measured POP aerosol-phase
      concentrations is presented to derive dry particulate depositional fluxes of POPs
      to the oceans. These fluxes are compared with those due to diffusive air-water
      exchange. For all polychlorinated biphenyl (PCB) congeners and lower chlorinated
      dibenzo-p-dioxins and furans (PCDD/Fs), air-water exchange dominates the dry
      deposition mechanism. However, this tendency reverses in some areas, such as in
      marine aerosol influenced areas and dust outflow regions, consistent with the
      important variability encountered for the depositional fluxes. Seasonal
      variability is mainly found in mid-high latitudes, due to the important influence
      of wind speed enhancing dry deposition fluxes and temperature as a driver of the
      gas-particle partitioning of POPs. The average dry aerosol deposition flux of
      sigmaPCBs and sigmaPCDD/Fs to the Atlantic Ocean is calculated to be in the order
      of 66 ng m(-2) yr(-1) and 9 ng m(-2)yr(-1) respectively. The total dry aerosol
      deposition of sigmaPCBs and sigmaPCDD/Fs to the Atlantic Ocean is estimated to be
      2200 kg yr(-1) and 500 kg yr(-1), respectively, while the net air-water exchange
      is higher, 22000 kg sigmaPCBs yr(-1) for PCBs and 1300 kg sigmaPCDD/Fs yr(-1).
      Furthermore, it is suggested that marine aerosol plays an important role in
      scavenging atmospheric contaminants.

PMID- 15575266
TI  - Seasonal and spatial variation of polychlorinated naphthalenes and non-/mono
      ortho-substituted polychlorinated biphenyls in arctic air.
AB  - Archived extracts of weekly air samples collected at remote arctic monitoring
      stations at Alert and Tagish, Canada, and Dunai Island, Russia, in 1994-1995 were
      combined into 4-week composites and analyzed for levels and seasonal trends of
      polychlorinated naphthalenes (PCNs) and non- and mono-ortho-substituted
      polychlorinated biphenyls (PCBs). Mean annual sigmaPCN concentrations were 0.69,
      0.82, and 0.38 pg/m3 at Alert, Dunai, and Tagish, respectively. PCNs exhibited a
      seasonal trend at Alert and Dunai, with higher levels occurring during winter
      when air masses originating over Eurasia influence the high arctic and coincide
      with the haze period. Episodic, trans-Pacific transport impacted PCN
      concentrations at Tagish. A seasonal trend was not evident for the non-/mono-o
      PCBs. The contrary PCN and non-/mono-o-PCB trends indicate that the sources of
      these two compound classes to arctic air differ, and that atmospheric transport
      from source regions has a greater influence on PCN levels than for non-/ mono-o
      PCBs. PCNs apparently originating from combustion sources contribute to levels in
      winter, as indicated by the presence of combustion marker congeners, but
      evaporative emissions from source regions are likely the dominant source. PCNs
      contributed 71 and 75% of dioxin toxic equivalents (TEQ) relative to the non
      /mono-o-PCBs at Alert and Dunai and 30% at Tagish during the winter months,
      demonstrating the toxicological importance of PCNs as a compound class relative
      to PCBs.

PMID- 15575267
TI  - Analysis of perfluorinated acids at parts-per-quadrillion levels in seawater
      using liquid chromatography-tandem mass spectrometry.
AB  - Perfluorinated acids (PFAs) and their salts have emerged as an important class of
      global environmental contaminants. Determination of sub-parts-per-trillion or
      parts-per-quadrillion concentrations of perfluorinated acids in aqueous media has
      been impeded by relatively high background levels arising from procedural or
      instrumental blanks. To understand the role of the oceans in the transport and
      fate of perfluorinated acids, methods to determine ultratrace levels of these
      compounds in seawater are needed. In this study, sources of procedural and
      instrumental blank contamination by perfluorinated acids have been identified and
      eliminated, to reduce background levels in blanks and thereby improve limits of
      quantitation. The method developed in this study is capable of detecting
      perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHS),
      perfluorobutanesulfonate (PFBS), perfluorooctanoate (PFOA), perfluorononanoate
      (PFNA), and perfluorooctanesulfonamide (PFOSA) at low pg/L levels in oceanic
      waters. PFOA is the major perfluorinated compound detected in oceanic waters,
      followed by PFOS. Further studies are being conducted to elucidate the
      distribution and fate of perfluorinated acids in oceans.

PMID- 15575268
TI  - Pyromorphite growth on lead-sulfide surfaces.
AB  - Electrochemical Scanning Tunneling Microscopy (EC-STM) and electron microscopies
      have been used to follow the nucleation and growth of approximately 10-15 nm
      pyromorphite (Pb5(PO4)3Cl,OH) particles on a galena (PbS) substrate under
      oxidative conditions. The particle sizes and crystal morphologies are found to be
      strongly affected by solution and oxidation potential, and in the earliest stages
      the particles are generally sufficiently small to be mobilized in a soil. It is
      clear that the particles grow epitaxially under these conditions, based on
      observations of the particles' adherence to the surface during imaging, their
      preferred crystallographic orientation, their growth along surface features on
      the galena, and commensurate atomic structures. Through cyclic voltammetry, we
      show that the presence of phosphate also partially passivates the surface of the
      galena to oxidation. We propose two possibilities for the mechanism of
      passivation, one is that pyromorphite nucleation inhibits the retreat of steps,
      and the second is that adsorbed phosphate stabilizes a lead-terminated surface
      structure by coordinating lead and slowing its dissolution.

PMID- 15575269
TI  - Inhibited Cr(VI) reduction by aqueous Fe(II) under hyperalkaline conditions.
AB  - This study investigated Cr(VI) reduction by dissolved Fe(II) in hyperalkaline pH
      conditions as found in fluid wastes associated with the U.S. nuclear weapons
      program. The results show that Cr(VI) reduction by Fe(II) at alkaline pH
      solutions proceeds very quickly. The amount of Cr(VI) removed from solution and
      the amount reduced increases with Fe(II):Cr(VI) ratio. However, the Cr(VI)
      reduction under alkaline pH condition is nonstoichiometric, probably due to
      Fe(II) precipitation and mixed iron(III)-chromium-(III) (oxy)hydroxides blocking
      Fe(II) surface sites, as well as removing Fe(II) from solution through O2
      oxidation. After Cr(VI) was reduced to Cr(III), it precipitated out as mixed
      Fe(x)Cr1-xO3(solids) and various Fe(III) precipitates with an overall Cr:Fe ratio
      of 1:3; all Cr remaining in the solution phase was unreduced Cr(VI). EXAFS data
      showed that Cr-O and Cr-Cr distances in the precipitates equal to 1.98 and 3.01
      A, respectively, consistent with the spinel-type structure as chromite.

PMID- 15575270
TI  - Box model investigation of the effect of soot particles on ozone downwind from an
      urban area through heterogeneous reactions.
AB  - Soot can provide additional surface area where heterogeneous reactions can take
      place in the atmosphere. These reactions are dependent on the number of reactive
      sites on the soot surface rather than the soot surface area per se. A box model,
      MOCCA, is used to investigate the effects of introducing heterogeneous reactions
      on soot into air parcel passing over an urban area and traveling downwind. The
      model was run at two soot mass concentrations of 2 microg/m3 and 20 microg/m3
      with a surface density of n-hexane and decane. Signifcant change in gasphase
      concentration was only observed for the higher soot concentration. Due to the
      noncatalytic nature of the heterogeneous reactions, soot sites are rapidly
      consumed, and soot site concentrations are greatly reduced shortly after
      emissions are turned off. Notable changes in gaseous concentrations due to the
      introduction of heterogeneous reactions are not observed in the urban setting.
      The impact of heterogeneous reactions is more evident after emissions are turned
      off (i.e. downwind from the urban center). These changes are minimal for the
      condition that used n-hexane surface density. For conditions that used decane
      soot, NOx concentrations showed a slight increase, with NO being higher in the
      daytime and NO2 at night. The maximum O3 reduction observed when using the higher
      soot concentration is 7 ppb, downwind of the urban center. Change in O3
      concentration was less than 1 ppb when using the lower soot loading. The observed
      effects of heterogeneous reactions on soot decrease with time.

PMID- 15575271
TI  - Fate of chlorinated fatty acids in migrating sockeye salmon and their transfer to
      arctic grayling.
AB  - To investigate whether biotransport constitutes an entry route into pristine
      ecosystems for nonpersistent, nonvolatile xenobiotic compounds, extractable
      organically bound halogen in sockeye salmon (Oncorhynchus nerka) from Alaska was
      determined before and after spawning migration. The major organohalogen compounds
      in the salmon were halogenated fatty acids, predominantly chlorinated species
      that accounted for up to 35% of the extractable, organically bound chlorine
      (EOCl) in the fish tissues. The amount of chlorinated fatty acids in the salmon
      muscle decreased as a result of spawning migration. The decrease was correlated
      with that of triacylglycerols in the salmon muscle, indicating the chlorinated
      fatty acids to be mobilized and metabolized to approximately the same extent as
      the other fatty acids. Chlorinated fatty acids were also transferred to the
      maturing roe in a manner similar to that of the unchlorinated fatty acids. Lipids
      of the Arctic grayling (Thymallus arcticus), a fish resident to the spawning lake
      of the salmon, contained higher concentrations of chlorinated fatty acids than
      grayling in a lake without migratory salmon. This may reflect a food-chain
      transfer of the chlorinated fatty acids originating from the salmon,
      demonstrating a long-range transport route for this type of pollutants to
      pristine areas.

PMID- 15575272
TI  - Gas-phase HO-initiated reactions of elemental mercury: kinetics, product studies,
      and atmospheric implications.
AB  - Mercury is an environmentally volatile toxic fluid metal that is assumed to have
      a long atmospheric residence time and hence is subject to long-range transport.
      The speciation and chemical transformation of mercury in the atmosphere strongly
      influences its bioaccumulation potential in the human food chain as well as its
      global cycling. To investigate the oxidation of Hg0 by HO, the dominantdaytime
      atmospheric oxidant, we performed kinetic and product studies over the
      temperature range 283-353 K under near atmospheric pressure (100+/-0.13 kPa) in
      air and N2 diluents. Experiments were carried out by the relative rate method
      using five reference molecules and monitored by gas chromatography with mass
      spectroscopic detection (GC-MS). The HO were generated using UV photolysis of
      isopropyl nitrite at 300 < or = lambda < or = 400 nm in the presence of NO. The
      room-temperature rate constant was found to be (9.0+/-1.3) x 10(-14) cm3
      molecule(-1) s(-1). The temperature dependence of the reaction can be expressed
      as a simple Arrhenius expression (in unit of 10(-14) cm3 molecule(-1) s(-1))
      using ethane as the reference molecule: kHg + HO = 3.55 x 10(-14) exp((294+/
      16)/T). The major reaction product, HgO, was identified in the gaseous form, as
      aerosols and as deposits on the container walls, using chemical ionization mass
      spectrometry (CI-MS), electron impact mass spectrometry (EI-MS), GC-MS, and cold
      vapor atomic fluorescence spectrometry (CVAFS). Experimental results reveal that
      ca. 6% of the reaction products were collected on a 0.2 microm filter as
      suspended aerosol, ca. 10% were in the gaseous form, and about 80% were deposited
      on the reaction vessel wall. The potential implications of our results in the
      understanding of tropospheric mercury transformation are herein discussed.

PMID- 15575273
TI  - Study of the OH and Cl-initiated oxidation, IR absorption cross-section,
      radiative forcing, and global warming potential of four C4-hydrofluoroethers.
AB  - Infrared absorption cross-sections and OH and Cl reaction rate coefficients for
      four C4-hydrofluoroethers (CF3)2CHOCH3, CF3CH2OCH2CF3, CF3CF2CH2OCH3, and
      CHF2CF2CH2OCH3 are reported. Relative rate measurements at 298 K and 1013 hPa of
      OH and Cl reaction rate coefficients give k(OH+(CF3)2CHOCH3) = (1.27+/-0.13) x
      10(-13), k(OH+CF3CH2OCH2CF3) = (1.51+/-0.24) x 10(-13), k(OH+CF3CF2CH2OCH3) =
      (6.42+/-0.33) x 10(-13), k(OH+CHF2CF2CH2OCH3) = (8.7 +/-0.5) x 10(-13),
      k(Cl+(CF3)2CHOCH3) = (8.4+/-1.3) x 10(-12), k(Cl+CF3CH2OCH2CF3) = (6.5+/-1.7) x
      10(-13), k(Cl+CF3CF2CH2OCH3) = (4.0+/-0.8) x 10(-11), and k(Cl+CHF2CF2CH2OCH3) =
      (2.65+/-0.17) x 10(-11) cm3 molecule(-1) s(-1). The primary products of the OH
      and Cl reactions with the fluorinated ethers have been identified as esters, and
      OH and Cl reaction rate coefficients for one of these, CF3CH2OCHO, are reported:
      k(OH+CF3CH2OCHO) = (7.7+/-0.9) x 10(-14) and kCl+CF3CH2OCHO) = (6.3+/-1.9) x 10(
      14) cm3 molecule(-1) s(-1) The rate coefficient for the Cl-atom reaction with
      CHF2CH2F is derived as k(Cl+CHF2CH2F) = (3.0+/-0.9) x 10(-14) cm3 molecule(-1) s(
      1) at 298 K. The error limits include 3sigma from the statistical data analyses
      as well as the errors in the rate coefficients of the reference compounds
      employed. The tropospheric lifetimes of the hydrofluoroethers are estimated to be
      short tauOH((CF3)2CHOCH3) approximately 100 days, tauOH(CF3CH2OCH2CF3)
      approximately 80 days, tauOH(CF3CF2CH2OCH3) approximately 20 days, and
      tauOH(CHF2CF2CH2OCH3) approximately 14 days, and their global warming potentials
      are small compared to CFC-11.

PMID- 15575274
TI  - Aqueous chlorination kinetics of some endocrine disruptors.
AB  - The aqueous chlorination kinetics of six endocrine disruptors (EDs: 4-n
      nonylphenol, beta-estradiol, estrone, estriol, 17alpha-ethinylestradiol,
      progesterone) were studied in the 3.50-12.00 pH range, at 20+/-2 degrees C, in
      the presence of an excess of total chlorine. Under these conditions, all
      molecules with a phenolic group in their structure were rapidly oxidized by
      chlorine, whereas progesterone remained unchanged. In the first step, apparent
      kinetic rate constants were determined at various pH levels. Then each elementary
      reaction kinetic rate constant, i.e., the reaction of hypochlorous acid (HOCl)
      with ionized EDs and neutral EDs and an acid-catalyzed reaction of HOCl with
      neutral EDs, was calculated in the second step. The results showed that
      chlorination exhibits a second-order reaction rate. The rate constants for the
      acid-catalyzed reaction ranged from 3.02 x 10(4) M(-1) s(-1) (for 4-n
      nonylphenol) to 1.82-2.62 x 10(5) M(-1) s(-1) (for hormones). The rate constants
      of HOCI reactions with ionized EDs were found to be equal to 7.5 x 10(4) M(-1) s(
      1) (for 4-n-nonylphenol) and between 3.52 and 4.15 x 10(5) M(-1) s(-1) (for
      hormones), while the rate contants of HOCI with neutral EDs were much lower,
      i.e., between 1.31 M(-1) s(-1) (for 4-n-nonylphenol) and 3.74-4.82 M(-1) s(-1)
      (for hormones). At pH 7, the apparent-second-order rate constants were calculated
      to range from 12.6 to 131.1 M(-1) s(-1). For a total chlorine concentration of 1
      mg/L, the corresponding half-life times at pH 7 were about 65 min for 4-n
      nonylphenol and 6-8 min for hormones.

PMID- 15575275
TI  - Lead phosphate minerals: solubility and dissolution by model and natural ligands.
AB  - Due to their relatively low solubility, lead-phosphate minerals may control Pb
      solution levels at a low value in natural environments. We reportthe solubility
      of Pb from two lead-orthophosphate mineral suspensions (beta-Pb9(PO4)6 and
      PbHPO4) after aging for 3 years. Lead (Pb2+) activity in the aged suspensions was
      compared to the activity calculated using the Ksp values of various Pb-PO4
      minerals reported in the literature. We also determine the time-dependent
      dissolution of the aged lead-phosphate minerals by organic and inorganic ligands
      containing S-functional groups (cysteine, methionine, and thiosulfate) and by a
      soil extracted humic acid. We find the activity of Pb2+ in the aged lead
      phosphate suspensions to be 1-2 orders of magnitude higher than predicted by the
      Ksp values reported in the literature. Disagreement between measured and Ksp
      calculated activities has been reported in other investigations of Pb-PO4
      minerals; we compiled some of the data and present them together with our
      results. Furthermore, the time-dependent dissolution experiments indicate that,
      in most cases, lead phosphates are partly dissolved in the presence of soluble
      ligands, i.e., model sulfides and humic acid. The soil-extracted humic acid
      enhanced the dissolution of Pb from the high pH (7.2) lead-phosphate (beta
      Pb9(PO4)6) mineral while suppressing Pb dissolution from the low pH (3.8) lead
      phosphate (PbHPO4) mineral. While the low molecularweight sulfur-containing
      ligands enhanced Pb dissolution, their effect was less pronounced. We conclude
      that (i) nonequilibrium conditions prevail in the mineral suspensions even after
      3 years of aging; and (ii) soluble ligands present in soils, sediments, and
      natural waters can potentially dissolve Pb from lead-phosphate minerals; such
      ligands, then, may enhance the biological availability and mobility of Pb in the
      environment.

PMID- 15575276
TI  - Cryogenic laser induced fluorescence characterization of U(VI) in Hanford Vadose
      Zone pore waters.
AB  - Ambient and liquid helium temperature laser-induced time-resolved uranyl
      fluorescence spectroscopy was applied to study the speciation of aqueous uranyl
      solutions containing carbonate and phosphate and two porewater samples obtained
      by ultracentrifugation of U(VI)-contaminated sediments. The significantly
      enhanced fluorescence signal intensity and spectral resolution found at liquid
      helium temperature allowed, for the first time, direct fluorescence spectroscopic
      observation of the higher aqueous uranyl complexes with carbonate: UO2(CO3)2(2-),
      UO2(CO3)3(4-), and (UO2)2(OH)3CO3-. The porewater samples were nonfluorescent at
      room temperature. However, at liquid helium temperature, both porewater samples
      displayed strong, well-resolved fluorescence spectra. Comparisons of the
      spectroscopic characteristics of the porewaters with those of the standard uranyl
      carbonate complexes confirmed that U(VI) in the porewaters existed primarily as
      UO2(CO3)3(4-) along with a small amount of other minor components, such as
      dicalcium-urano-tricarbonate complex, Ca2UO2(CO3)3, consistent with thermodynamic
      calculation. The U(VI)-carbonate complex is apparently the mobile species
      responsible for the subsurface migration of U(VI), even though the majority of
      the in-ground U(VI) inventory at the site from which the samples were obtained
      exists as intragrain U(VI)-silicate precipitates.

PMID- 15575277
TI  - Use of ferrocenyl surfactants of varying chain lengths to study electron transfer
      reactions in native montmorillonite clay.
AB  - A series of ferrocenyl surfactants was tested as model compounds to study
      electron transfer reactions involving structural Fe(III) in clay minerals. The
      surfactants contain trimethylammonium headgroups, ferrocene tail groups, and
      intervening hydrocarbon chain lengths of one, six, or 11 carbons. Two factors
      considered to be decisive for electron transfer were addressed: (1) physical
      access of the surfactant ferrocene to the reactive sites through hexagonal holes
      in the clay lattice by X-ray diffraction (XRD) and small-angle X-ray scattering
      (SAXS) and (2) thermodynamic favorability of the overall oxidation/reduction
      reaction based on experimentally determined oxidation/reduction potentials. In
      suspensions of clay with the longer chain surfactants,
      (ferrocenylhexyl)trimethylammonim (FHTMA+) and
      (ferrocenylundecyl)trimethylammonium (FUTMA+), where electron transfer may be
      expected to be favored by both factors, physical accessibility, and thermodynamic
      favorability, ferroecene oxidation was observed by diffuse reflectance infrared
      spectroscopy (DRIFT), ultraviolet-visible spectroscopy (UV-vis), and visual color
      changes. In contrast, the shorter chain length surfactant,
      (ferrocenylmethyl)trimethylammonium (FMTMA+), did not participate in electron
      transfer with the clay, as substantiated by UV-vis and no visible color changes.
      Rigid conformation and/or higher oxidation/reduction potential than clay Fe can
      accountforthe lack of reaction. The utility and limitations of using these
      surfactants as model compounds is discussed.

PMID- 15575278
TI  - Origin of oxygen in sulfate during pyrite oxidation with water and dissolved
      oxygen: an in situ horizontal attenuated total reflectance infrared spectroscopy
      isotope study.
AB  - FeS2 (pyrite) is known to react with water and dissolved molecular oxygen to form
      sulfate and iron oxyhydroxides. This process plays a large role in the
      environmentally damaging phenomenon known as acid mine drainage. An outstanding
      scientific issue has been whether the oxygen in the sulfate and oxyhydroxide
      product was derived from water and/or dissolved oxygen. By monitoring the
      reaction in situ with horizontal attenuated total reflectance infrared
      spectroscopy, it was found that when using 18O isotopically substituted water,
      the majority of the infrared absorbance due to sulfate product red-shifted
      approximately 70 cm(-1) relative to the absorbance of sulfate using H(2)16O as a
      reactant. Bands corresponding to the iron oxyhydroxide product did not shift.
      These results indicate water as the primary source of oxygen in the sulfate
      product, while the oxygen atoms in the iron oxyhydroxide product are obtained
      from dissolved molecular oxygen.

PMID- 15575279
TI  - Transformation of the antibacterial agent sulfamethoxazole in reactions with
      chlorine: kinetics, mechanisms, and pathways.
AB  - Sulfamethoxazole (SMX)--a member of the sulfonamide antibacterial class--has been
      frequently detected in municipal wastewater and surface water bodies in recent
      years. Kinetics, mechanisms, and products of SMX in reactions with free chlorine
      (HOCl/OCl-) were studied in detail to evaluate the effect of chlorination
      processes on the fate of sulfonamides in municipal wastewaters and affected
      drinking waters. Direct reactions of free available chlorine (FAC) with SMX were
      quite rapid. A half-life of 23 s was measured under pseudo-first-order conditions
      ([FAC]0 = 20 microM (1.4 mg/L) and [SMX]0 = 2 microM) at pH 7 and 25 degrees C in
      buffered reagent water. In contrast, a half-life of 38 h was determined for
      reactions with combined chlorine (NH2Cl, NHCl2) under similar conditions. Free
      chlorine reaction rates were first-order in both substrate and oxidant, with
      specific second-order rate constants of 1.1 x 10(3) and 2.4 x 10(3) M(-1) s(-1)
      for SMX neutral and anionic species, respectively. Investigations with
      substructure model compounds and identification of reaction products verified
      that chlorine directly attacks the SMX aniline-nitrogen, resulting in (i)
      halogenation of the SMX aniline moiety to yield a ring-chlorinated product at sub
      stoichiometric FAC concentrations (i.e., [FAC]0:[SMX]0 < or = 1) or (ii) rupture
      of the SMX sulfonamide moiety in the presence of stoichiometric excess of FAC to
      yield 3-amino-5-methylisoxazole, SO4(2-) (via SO2), and N-chloro-p
      benzoquinoneimine. Reaction ii represents an unexpected aromatic amine
      chlorination mechanism that has not previously been evaluated in great detail.
      Experiments conducted in wastewater and drinking water matrixes appeared to
      validate measured reaction kinetics for SMX, indicating that SMX and likely other
      sulfonamide antibacterials should generally undergo substantial transformation
      during disinfection of such waters with free chlorine residuals.

PMID- 15575280
TI  - Apparent decreases in colloid deposition rate coefficients with distance of
      transport under unfavorable deposition conditions: a general phenomenon.
AB  - The transport of polystyrene microspheres was examined in packed glass beads
      under a variety of environmentally relevant ionic strength and flow conditions.
      The observed profiles of numbers of retained microspheres versus distance from
      the column entrance were much steeper than expected based on a constant rate
      coefficient of deposition acrossthe length of the column, indicating apparent
      decreases in deposition rate coefficients with transport distance. Deviation in
      the profile from log-linear decreases with distance was greatest under highly
      unfavorable conditions (low ionic strength), relatively reduced under mildly
      unfavorable conditions (high ionic strength), and was eliminated under favorable
      conditions. The generality of apparent decreases in deposition rate coefficients
      with distance of transport among microspheres, bacteria, and viruses leads to the
      conclusion that such effects reflect processes that are fundamental to filtration
      under unfavorable conditions. Numerical simulations of experiments that were
      performed under unfavorable conditions utilized a log-normal distribution of
      deposition rate coefficients among the colloid population in orderto simulate the
      effluent curves and retained profiles simultaneously. It is shown that while
      straining could be a significant contributor to the steep retained profiles at
      low ionic strength, where overall retention is low, distribution in interaction
      potentials among the population was a viable mechanism that can yield apparent
      decreases in deposition rate coefficients with distance of transport.

PMID- 15575281
TI  - Sorption and desorption of Cd2+ and Zn2+ ions in apatite-aqueous systems.
AB  - As a low-soluble phosphate mineral capable of binding various metal ions, apatite
      can be used to immobilize toxic metals in soils and waters. In the present
      research the factors affecting sorption and desorption of Cd2+ and Zn2+ ions
      on/from apatites are investigated. Batch experiments were carried out using
      synthetic hydroxy-, fluoride-, and carbonate-substituted apatites having various
      specific surface area (SSA). Apatite sorption capacity was found to depend mainly
      on its SSA, ranging from 16 to 78 and from 11 to 79 mmol per 100 g of apatite for
      Cd2+ and Zn2+, respectively. The solution composition (pH, and presence of Cl-
      and NO3- ions) had no essential impact on sorption. Desorption of bound cations
      depended both on the sorption level and solution composition. The amount of
      desorbed Cd2+ and Zn2+ increased proportionally to the amount of sorbed cations.
      However, apatites having higher sorption capacity release relatively less sorbed
      cations. Desorption increases with increasing Ca2+ concentration in the solution,
      reaching 8-20% of sorbed Cd2+ in 0.002 M, 10-35% in 0.01 M, and 33-45% in 0.05 M
      Ca(NO3)2 solution. Compared to nitrate solutions, the presence of Cl- ions in the
      solution promotes the release of bound cations. Desorption of Zn2+ is slightly
      higher than that of Cd2+. The desorption mechanism was assumed to include both
      ion-exchange and adsorption of Ca2+ ions on apatite surface.

PMID- 15575282
TI  - Three-dimensional dual-morphotype species modeling of activated sludge flocs.
AB  - An individual-based model, originally developed for a biofilm system, was adapted
      to simulate three-dimensional formation of activated sludge flocs. The model was
      extended to two different bacterial morphotypes (floc-forming and filamentous
      bacteria), allowing spatial development of the floc according to the bacterial
      morphology, diffusion, reaction, and growth processes. The model needed also
      extension with a process for attachment of individual cells. Despite being in an
      early stage of development, the model is already a tool that enables us to obtain
      useful information about the microfloc environment. The model indicates that
      filamentous bacterial morphology and substrate microgradients are important
      aspects in the formation of bacterial structures. In mass transport-limited
      regimes filamentous bacterial structures prevail, whereas in growth-limited
      regimes irregular shaped flocs with fingerlike structures are dominant. These
      modeling results suggest that activated sludge flocs and biofilms might be
      different manifestations of the same phenomena. The model results support the
      hypothesis that floc-macrogradients can be the most important parameter for
      development of bulking sludge. The model suggests that attachment has a very
      strong effect on floc structure, leading to enhancement of the effect of
      substrate microgradients.

PMID- 15575283
TI  - Uptake of bromide by two wetland plants (Typha latifolia L. and Phragmites
      australis (Cav.) Trin. ex Steud).
AB  - The successful use of bromide (Br-) as a conservative tracer for hydrological
      tests in wetland systems requires minimal Br- loss due to plant uptake. The
      uptake of Br- by two wetland plants, cattail (Typha latifolia L.) and reed grass
      (Phragmites australis (Cav.) Trin. ex Steud), was investigated in greenhouse flow
      through microcosms. Concentrations of Br- and other pertinent constituents in
      sediment pore water were measured at 2 cm depth increments in the sediment
      column. The vertical Br- concentration profiles in the sediments clearly revealed
      Br- uptake by T. latifolia and by P. australis. X-ray spectroscopy studies of
      bromine in plant samples revealed the accumulation of Br- in root and leaf
      tissues. Plant transpiration was found to significantly concentrate dissolved
      species in sediments and was accounted for in the calculations of Br uptake
      rates. Michaelis-Menten kinetics satisfactorily describe Br- uptake by T.
      latifolia. The uptake of Br- by P. australis, however, showed unique features
      that could not be described using Michaelis-Menten kinetics. The addition of
      chloride (Cl-) effectively inhibited Br- uptake, and the uptake of Cl- and Br- by
      T. latifolia was shown to follow dual-substrate Michaelis-Menten kinetics.
      Results of this study indicate that the use of Br- for tracer experiments in
      vegetated wetland systems should be evaluated with great caution.

PMID- 15575284
TI  - Microbial reduction of U(VI) at the solid-water interface.
AB  - Microbial (Geobacter sulfurreducens) reduction of 0.1 mM U(VI) in the presence of
      synthetic Fe(III) oxides and natural Fe(III) oxide-containing solids was
      investigated in pH 6.8 artificial groundwater containing 10 mM NaHCO3. In most
      experiments, more than 95% of added U(VI) was sorbed to solids, so that U(VI)
      reduction was governed by reactions at the solid-water interface. The rate and
      extent of reduction of U(VI) associated with surfaces of synthetic Fe(III) oxides
      (hydrous ferric oxide, goethite, and hematite) was comparable to that observed
      during reduction of aqueous U(VI). In contrast, microbial reduction of U(VI)
      sorbed to several different natural Fe(III) oxide-containing solids was slower
      and less extensive compared to synthetic Fe(III) oxide systems. Addition of the
      electron shuttling agent anthraquinone-2,6-disulfonate (AQDS; 0.1 mM) enhanced
      the rate and extent of both Fe(III) and U(VI) reduction. These findings suggest
      that AQDS facilitated electron transfer from G. sulfurreducens to U(VI)
      associated with surface sites atwhich direct enzymatic reduction was kinetically
      limited. Our results demonstrate that association of U(VI) with diverse surface
      sites in natural soils and sediments has the potential to limit the rate and
      extent of microbial U(VI) reduction and thereby modulate the effectiveness of in
      situ U(VI) bioremediation.

PMID- 15575285
TI  - Cd and proton adsorption onto bacterial consortia grown from industrial wastes
      and contaminated geologic settings.
AB  - To model the effects of bacterial metal adsorption in contaminated environments,
      results from metal adsorption experiments involving individual pure stains of
      bacteria must be extrapolated to systems in which potentially dozens of bacterial
      species are present. This extrapolation may be made easier because bacterial
      consortia from natural environments appear to exhibit similar metal binding
      properties. However, bacteria that thrive in highly perturbed contaminated
      environments may exhibit significantly different adsorptive behavior. Here we
      measure proton and Cd adsorption onto a range of bacterial consortia grown from
      heavily contaminated industrial wastes, groundwater, and soils. We model the
      results using a discrete site surface complexation approach to determine binding
      constants and site densities for each consortium. The results demonstrate that
      bacterial consortia from different contaminated environments exhibit a range of
      total site densities (approximately a 3-fold difference) and Cd-binding constants
      (approximately a 10-fold difference). These ranges for Cd binding constants may
      be small enough to suggest that bacteria-metal adsorption in contaminated
      environments can be described using relatively few "averaged" bacteria-metal
      binding constants (in conjunction with the necessary binding constants for
      competing surfaces and ligands). However, if additional precision is necessary,
      modeling parameters must be developed separately for each contaminated
      environment of interest.

PMID- 15575286
TI  - Measures of overall persistence and the temporal remote state.
AB  - The overall persistence, Pov, has been suggested as an indicator that integrates
      single media half-lives and phase partitioning. However, the application of this
      indicator is hindered by the fact that there are different definitions of Pov and
      that the most common measure of Pov, the residence time at steady state, depends
      heavily on the release pattern. Here, different measures are compared that can be
      used to compute Pov from the mass of a chemical in the environment as a function
      of time in a dynamic multimedia model. These measures include the equivalence
      width, which corresponds to the residence time at steady state, the mean value of
      the function of mass vs time ("mean time"), and the clearance time. The temporal
      remote state is defined as the state of the model system long after the stop of
      emissions; it is independent of the release pattern of a chemical. The mean time
      in the temporal remote state reflects the long-term removal rate of a chemical
      and is used as a persistence benchmark. Correlations of the three measures of Pov
      to the persistence benchmark are analyzed. The maximum equivalence width, which
      is obtained with release to one of the media air, water, or soil, is a good
      approximation of the mean time in the temporal remote state. Because the maximum
      equivalence width is identical to the maximum residence time at steady state, the
      mean time in the temporal remote state can be estimated with existing steady
      state models.

PMID- 15575287
TI  - Development of a physiologically based pharmacokinetic model for volatile
      fractions of gasoline using chemical lumping analysis.
AB  - Physiologically based pharmacokinetic (PBPK) models have often been used to
      describe the absorption, distribution, metabolism, and excretion of chemicals in
      animals but have been limited to single chemicals and simple mixtures due to the
      numerous parameters required in the models. To overcome the barrier to modeling
      more complex mixtures, we used a chemical lumping approach, used in the past in
      chemical engineering but not in pharmacokinetic modeling, in a rat PBPK model for
      gasoline hydrocarbons. Our previous gasoline model consisted of five individual
      components (benzene, toluene, ethylbenzene, xylene, and hexane) and a lumped
      chemical that included all remaining components of whole gasoline. Despite being
      comprised of hundreds of components, the lumped component could be described
      using a single set of chemical parameters that depended on the blend of gasoline.
      In the present study, we extend this approach to evaporative fractions of
      gasoline. The PBPK model described the pharmacokinetics of all of the volatility
      weighted fractions of gasoline when differences in partitioning and metabolism
      between fractions were taken into account. Adjusting the ventilation rate
      parameter to account for respiratory depression at high exposures also allowed a
      much improved description of the data. At high exposure levels, gasoline
      components competitively inhibit each other's metabolism, and the model
      successfully accounted for binary interactions of this type, including between
      the lumped component and the five other chemicals. The model serves as a first
      example of how the engineering concept of chemical lumping can be used in
      pharmacokinetics.

PMID- 15575288
TI  - Geo-referenced multimedia environmental fate model (G-CIEMS): model formulation
      and comparison to the generic model and monitoring approaches.
AB  - A spatially resolved and geo-referenced dynamic multimedia environmental fate
      model, G-CIEMS (Grid-Catchment Integrated Environmental Modeling System) was
      developed on a geographical information system (GIS). The case study for Japan
      based on the air grid cells of 5 x 5 km resolution and catchments with an average
      area of 9.3 km2, which corresponds to about 40,000 air grid cells and 38,000
      river segments/catchment polygons, were performed for dioxins, benzene, 1,3
      butadiene, and di-(2-ethyhexyl)phthalate. The averaged concentration of the model
      and monitoring output were within a factor of 2-3 for all the media. Outputs from
      G-CIEMS and the generic model were essentially comparable when identical
      parameters were employed, whereas the G-CIEMS model gave explicit information of
      distribution of chemicals in the environment. Exposure-weighted averaged
      concentrations (EWAC) in air were calculated to estimate the exposure ofthe
      population, based on the results of generic, G-CIEMS, and monitoring approaches.
      The G-CIEMS approach showed significantly better agreement with the monitoring
      derived EWAC than the generic model approach. Implication for the use of a geo
      referenced modeling approach in the risk assessment scheme is discussed as a
      generic-spatial approach, which can be used to provide more accurate exposure
      estimation with distribution information, using generally available data sources
      for a wide range of chemicals.

PMID- 15575289
TI  - Mobile laboratory with rapid response instruments for real-time measurements of
      urban and regional trace gas and particulate distributions and emission source
      characteristics.
AB  - Recent technological advances have allowed the development of robust, relatively
      compact, low power, rapid response (approximately 1 s) instruments with
      sufficient sensitivity and specificity to quantify many trace gases and aerosol
      particle components in the ambient atmosphere. Suites of such instruments can be
      deployed on mobile platforms to study atmospheric processes, map concentration
      distributions of atmospheric pollutants, and determine the composition and
      intensities of emission sources. A mobile laboratory containing innovative
      tunable infrared laser differential absorption spectroscopy (TILDAS) instruments
      to measure selected trace gas concentrations at sub parts-per-billion levels and
      an aerosol mass spectrometer (AMS) to measure size resolved distributions of the
      nonrefractory chemical components of fine airborne particles as well as selected
      commercial fast response instruments and position/velocity sensors is described.
      Examples of the range of measurement strategies that can be undertaken using this
      mobile laboratory are discussed, and samples of measurement data are presented.

PMID- 15575290
TI  - New method for time-resolved diesel engine exhaust particle mass measurement.
AB  - The Dekati mass monitor (DMM; Dekati Ltd., Finland), a relatively new real-time
      mass measurement instrument, was investigated in this project. In contrast to the
      existing gravimetric filter method also used as a standard for regulation
      purposes, this instrument provides second-by-second data on mass concentration in
      the engine exhaust gas. The principle of the DMM is based on particle charging,
      inertial and electrical size classification, and electrical detection of aerosol
      particles. This study focuses on the instrument's practical performance. Details
      on calibration and the theory of operation will be published elsewhere. The
      exhaust emissions of two heavy-duty engines complying with the Euro III emission
      standard were measured on a dynamic engine test bench. We looked atthe particle
      number and mass emissions of the engines in different transient test cycles and
      steady-state conditions. The ability to follow transient test cycles and the
      response times of the DMM were investigated. The aerosol mass concentration
      measured by the DMM was compared with the mass concentration obtained by the
      standard gravimetric filter method with Teflon-coated glass fiber filters. The
      total mass concentration (integral over the whole cycle) measured by the DMM is
      about 20% higher than that measured by the standard gravimetric filter method.
      The total mass concentration from the DMM was also compared with the volume
      concentration calculated from the electrical low-pressure impactor (ELPI)
      measurements. Correlations were made with other particle measuring systems. The
      DMM correlates very well with the particulate mass (R2 = 0.95) and exhibits good
      linearity and repeatability. The response time to a well-defined change in
      exhaust concentration was observed to be fast and stable. The DMM was able to
      follow transient test cycles and provides good results on a second-by-second
      basis. The instrument used in this study was still under development, and there
      is therefore no complete scientific background reference for the DMM. This study
      therefore focuses more on the measurements than on the scientific background. The
      measurements have shown thatthe DMM is an adequate instrument for measuring the
      mass concentration of engine exhaust, with results comparable to those from the
      standard gravimetric filter method. In addition, the DMM provides real-time
      second-by-second data of the mass concentration during transient test cycles.

PMID- 15575291
TI  - Receptor modeling of toronto PM2.5 characterized by aerosol laser ablation mass
      spectrometry.
AB  - Urban Toronto fine particulate matter (PM2.5) was physically and chemically
      characterized by online aerosol laser ablation mass spectrometry (LAMS) between
      January 2002 and February 2003. The mass spectra from the analysis of individual
      aerosol particles were classified according to chemical composition by a neural
      network approach called adaptive resonance theory (ART-2a). Temporal trends of
      the hourly analysis rate of over 120 different particles types were constructed
      and subjected to positive matrix factorization (PMF). This receptor modeling
      technique enabled the identification of nine distinct emission sources
      responsible for these particle types: biogenic, mixed crustal, organic nitrate,
      construction dust, Toronto soil/road salt, secondary salt, wood burning,
      intercontinental dust, and an unknown source of aluminum fluoride dust. Episodic
      events occurred with the wood burning, intercontinental dust, and unknown dust
      sources. This is the first paper reporting the application of PMF to single
      particle spectral data.

PMID- 15575292
TI  - Anisotropic diffusion in layered argillaceous rocks: a case study with Opalinus
      Clay.
AB  - Anisotropic diffusion was studied in Opalinus Clay, a potential host rock for
      disposal of spent fuel, vitrified high-level waste, and long-lived intermediate
      level waste in Switzerland. Diffusion parallel to the bedding was measured using
      a radial through-diffusion technique and diffusion perpendicular to the bedding
      bythe classical (planar) through-diffusion technique. The samples used were from
      Mont Terri (MT) and from Benken (BE). Diffusion of HTO, 36Cl-, and 22Na+ parallel
      and perpendicular to the bedding was studied under confining pressures of 7 MPa
      (MT) and 14 MPa (BE). The results indicate that diffusion parallel to the bedding
      is faster than diffusion perpendicular to the bedding by a factor of 4-6 for the
      three radionuclides, indicating that the Opalinus Clay is anisotropic. This might
      be explained by smaller path lengths (tortuosity) for species diffusing parallel
      to the fabric. The degree of anisotropy is slightly smaller for Opalinus Clay
      from Mont Terri than from Benken. This is due to the lower overburden pressure in
      Mont Terri resulting in a lower preferential orientation of the clay platelets.

PMID- 15575293
TI  - Pumping-induced ebullition: a unified and simplified method for measuring
      multiple dissolved gases.
AB  - The incorporation of multiple dissolved gas measurements in biogeochemical
      studies remains a difficult and expensive challenge. Incompatibilities in
      collection, handling, and storage procedures generally force the application of
      multiple sampling procedures for multiple gases. This paper introduces the
      concept and application of pumping-induced ebullition (PIE), a unified approach
      for routine measurement of multiple dissolved gases in natural waters and
      establishes a new platform for development of in situ real-time dissolved gas
      monitoring tools. Ebullition (spontaneous formation of bubbles) is induced by
      pumping a water sample through a narrow-diametertube (a "restrictor") to decrease
      hydrostatic pressure (PH) below total dissolved gas pressure (PT). Buoyancy is
      used to trap bubbles within a collection tower where gas accumulates rapidly (1
      mL/min) to support multiple chemical analyses. Providing for field collection of
      an essentially unlimited and unified volume of gas sample, PIE afforded accurate
      and precise measurements of major (N2, 02, Ar), trace (CO2, N20, CH4) and
      ultratrace (CFC11, CFC12, CFC113, SF6) dissolved gases in Wisconsin groundwater,
      revealing interrelationships between denitrification, apparent recharge age
      dates, and historical land use. Compared to conventional approaches, PIE
      eliminates multiple gas-specific sampling methods, reduces data computations,
      simplifies laboratory instrumentation, and avoids aqueous production and
      consumption of biogenic gases during sample storage. A lake depth profile for CO2
      demonstrates PIE's flexibility as an in situ real-time platform for dissolved gas
      measurements. The apparent departures of some gases (SF6, H2, N2O, CO2) from
      solubility equilibrium behavior warrant further confirmation and theoretical
      investigation.

PMID- 15575294
TI  - Development of a solid-phase microextraction-based method for sampling of
      persistent chlorinated hydrocarbons in an urbanized coastal environment.
AB  - Solid-phase microextraction (SPME) has been used as an in situ sampling technique
      for a wide range of volatile organic chemicals, but SPME field sampling of
      nonvolatile organic pollutants has not been reported. This paper describes the
      development of an SPME-based sampling method employing a poly(dimethylsiloxane)
      (PDMS)-coated (100-microm thickness) fiber as the sorbent phase. The laboratory
      calibrated PDMS-coated fibers were used to construct SPME samplers, and field
      tests were conducted at three coastal locations off southern California to
      determine the equilibrium sampling time and compare the efficacy of the SPME
      samplers with that of an Infiltrex 100 water pumping system (Axys Environmental
      Systems Ltd., Sidney, British Columbia, Canada). p,p'-DDE and o,p'-DDE were the
      components consistently detected in the SPME samples among 42 polychlorinated
      biphenyl congeners and 17 chlorinated pesticidestargeted. SPME samplers deployed
      attwo locations with moderate and high levels of contamination for 18 and 30 d,
      respectively, attained statistically identical concentrations of p,p'-DDE and
      o,p'-DDE. In addition, SPME samplers deployed for 23 and 43 d, respectively, at a
      location of low contamination also contained statistically identical
      concentrations of p,p'-DDE. These results indicate that equilibrium could be
      reached within 18 to 23 d. The concentrations of p,p'-DDE, o,p'-DDE, or p,p'-DDD
      obtained with the SPME samplers and the Infiltrex 100 system were virtually
      identical. In particular, two water column concentration profiles of p,p'-DDE and
      o,p'-DDE acquired by the SPME samplers at a highly contaminated site on the Palos
      Verdes Shelf overlapped with the profiles obtained by the Infiltrex 100 system in
      1997. The field tests not only reveal the advantages of the SPME samplers
      compared to the Infiltrex 100 system and other integrative passive devices but
      also indicate the need to improve the sensitivity of the SPME-based sampling
      technique.

PMID- 15575295
TI  - Fate of carbon tetrachloride during phytoremediation with poplar under controlled
      field conditions.
AB  - The fate of carbon tetrachloride (CT) during phytoremediation with poplar was
      assessed by examining the transpiration of CT from leaves, diffusion from soil,
      tree trunks, and surface roots, and accumulation of chloride ion in soil and
      plant tissues. Feedwater containing 12-15 mg/L CT was added to the field test
      beds planted with poplar, and over 99% of the CT was removed. No significant
      amount of CT was transpired or diffused into the air, and no significant amount
      of CT-chlorine accumulated in the tree tissues. Chloride ion accumulated in the
      soil accounted for all of the CT-chlorine removed. When soils from the root zones
      were compared to unvegetated soils, microbial mineralization of CT was not
      enhanced in soils from the root zones as compared to unvegetated soils. Thus, we
      conclude that uptake and dechlorination of CT by plant tissues is likely the
      primary mechanism for phytoremediation by poplar.

PMID- 15575296
TI  - Colloid formation in Hanford sediments reacted with simulated tank waste.
AB  - Solutions of high pH, ionic strength, and aluminum concentration have leaked into
      the subsurface from underground waste storage tanks atthe Hanford Reservation in
      Washington State. Here, we test the hypothesis that these waste solutions alter
      and dissolve the native minerals present in the sediments and that colloidal
      (diameter < 2 microm) feldspathoids form. We reacted Hanford sediments with
      simulated solutions representative of Hanford waste tanks. The solutions
      consisted of 1.4 or 2.8 mol/kg NaOH, 0.125 or 0.25 mol/kg NaAlO4, and 3.7 mol/kg
      NaNO3 and were contacted with the sediments for a period of 25 or 40 days at 50
      degrees C. The colloidal size fraction was separated from the sediments and
      characterized in terms of mineralogy, morphology, chemical composition, and
      electrophoretic mobility. Upon reaction with tank waste solutions, native
      minerals released Si and other elements into the solution phase. This Si
      precipitated with the Al present in the waste solutions to form secondary
      minerals, identified as the feldspathoids cancrinite and sodalite. The solution
      phase was modeled with the chemical equilibrium model GMIN for solution
      speciation and saturation indices with respect to sodalite and cancrinite. The
      amount of colloidal material in the sediments increased upon reaction with waste
      solutions. At the natural pH found in Hanford sediments (pH 8) the newly formed
      minerals are negatively charged, similar to the unreacted colloidal material
      present in the sediments. The formation of colloidal material in Hanford
      sediments upon reaction with tank waste solutions is an important aspect to
      consider in the characterization of Hanford tank leaks and may affect the fate of
      hazardous radionuclides present in the tank waste.

PMID- 15575297
TI  - Identification and quantification of mineral precipitation in Fe0 filings from a
      column study.
AB  - Thermogravimetric analysis (TGA) combined with X-ray diffraction (XRD) was used
      to identify mineral phases and determine corrosion rates of granular iron samples
      from a 2-yr field column study. Similar to other studies, goethite, magnetite,
      aragonite, and calcite were found to be the major precipitated minerals, with
      Fe2(OH)2CO3 and green rust as minor phases. Based on TGA-mass spectrometry (MS)
      analysis, Fe0 corrodes at rates of 0.5-6.1 mmol kg(-1) d(-1) in the high NO3- (up
      to 13.5 mM) groundwater; this rate is significantly higher than previously
      reported. Porosity reduction was 40.6%-45.1% for the inlet sand/Fe0 interface and
      7.4%-25.6% for effluent samples of two test columns. Normalized for treatment
      volumes, porosity loss values are consistent with studies that use high levels of
      SO4(2-) but are higher than those using low levels of corrosive species. Aqueous
      mass balance calculations yield corrosion rates similar to the TGA-MS method,
      providing an alternative to coring and mineralogical analysis. A severely
      corroded iron sample from the column simulating a 17-yr treatment throughput
      showed >75% porosity loss. Extensive porosity loss due to high levels of
      corrosive species in groundwater will have significant impact on long-term
      performance of permeable reactive barriers.

PMID- 15575298
TI  - Efficient control system for low-concentration inorganic gases from a process
      vent stream: application of surfactants in spray and packed columns.
AB  - Control of low-concentration pollutants from a semiconductor process vent stream
      using a wet-scrubbing technique is a challenging task to meet Taiwan
      environmental emission standards. An efficient wet-scrubber is designed on a
      pilot scale and tested to control low concentration acid and base waste-gas
      emission. The scrubber system consisted of two columns, i.e., a fine spray column
      [cutoff diameter (based on volume), Dv(50) = 15.63 microm; Sauter mean diameter
      (SMD) = 7.62 microm], which is especially efficient for NH3 removal as the pH of
      the spraying liquid is approximately 7 followed by a packed column with a
      scrubbing liquid pH approximately 9.0 mainly for acids removal. It is observed
      that use of the surfactants in low concentration about 10(-4) M and 10(-7) M in
      the spray liquid and in the scrubbing liquid, respectively, remarkably enhances
      the removal efficiency of the system. A traditional packed column (without the
      spray column and the surfactant) showed that the removal efficiencies of NH3, HF,
      and HCl for the inlet concentration range 0.2 to 3 ppm were (n = 5) 22.6+/-3.4%,
      43.4+/-5.5%, and 40.4+/-7.4%, respectively. The overall efficiencies of the
      proposed system (the spray column and the packed column) in the presence of the
      surfactant in the spray liquid and in the scrubbing liquid forthese three species
      were found to increase significantly (n = 5) from 60.3+/-3.6 to 82.8+/-6.8%,
      59.1+/-2.7 to 83.4+/-4.2%, and 56.2+/-7.3 to 81.0+/-6.7%, respectively. In this
      work, development of charge on the gas-liquid interface due to the surfactants
      has been measured and discussed. It is concluded that the presence of charge on
      the gas-liquid interface is the responsible factor for enhancement of the removal
      efficiency (mass-transfer in liquid phase). The effects of the type of
      surfactants, their chain length, concentration in liquid, etc. on the removal
      efficiency are discussed. Since the pilot tests were performed under the
      operating conditions similar to most of the wet-scrubbers operated in
      semiconductors manufacturing facilities for inorganic pollutants, this study can
      be applied to modify the existing wet-scrubbers to enhance the removal
      efficiencies, especially for low-concentration pollutants.

PMID- 15575299
TI  - Discoloration and mineralization of Orange II using different heterogeneous
      catalysts containing Fe: a comparative study.
AB  - Four heterogeneous catalysts containing Fe including a bentonite-clay-based Fe
      nanocomposite (Fe-B), hematite (alpha-Fe2O3), amorphous FeOOH, and calcined FeOOH
      (denoted as FeOOH-M) were employed for the photo-Fenton discoloration and
      mineralization of 0.2 mM Orange II in the presence of 10 mM H2O2 and 8 W UVC at
      two different initial solution pH values (3.0 and 6.6). It was found that, at an
      initial solution pH of 3.0, their photocatalytic activities follow the order Fe-B
      > FeOOH, FeOOH-M > alpha-Fe2O3. When the Fe-B nanocomposite, FeOOH, and FeOOH-M
      were used as heterogeneous catalysts, both heterogeneous and homogeneous photo
      Fenton reactions were responsible for the discoloration and mineralization of 0.2
      mM Orange II because homogeneous photo-Fenton reaction occurred due to the
      presence of Fe ions leached from the catalysts. At an initial solution pH of 6.6,
      their photocatalytic activities still follow the order Fe-B > FeOOH, FeOOH-M >>
      alpha-Fe2O3. However, only heterogeneous photo-Fenton reaction accounted for the
      discoloration and mineralization of 0.2 mM Orange II because Fe leaching from the
      catalysts was significantly depressed. In the case of alpha-Fe2O3 as a catalyst,
      whether at an initial solution pH of 3.0 or 6.6, only heterogeneous photo-Fenton
      reaction happened for the discoloration and mineralization of 0.2 mM Orange II
      because Fe leaching from the catalyst is negligible. The apparent discoloration
      kinetics of Orange II with the four catalysts at two different initial solution
      pH values was also investigated.

PMID- 15575300
TI  - Influence of ultrasonic disintegration on sludge growth reduction and its
      estimation by respirometry.
AB  - Excess biomass generation during wastewater treatment is a great threat to the
      ecology if it is not properly disposed. Sludge growth reduction is one of the
      best ways to alleviate the problem. The present study focused in this direction
      employs ultrasound to disintegrate the floc without causing cell disruption. It
      has been found that a major size reduction that takes place at a lower energy
      input (3000 kJ/kg) and a further increase in energy input results only in minor
      changes. Sludge growth reduction is found to be of the order of 29% and energy
      efficient under flowthrough conditions. The effect of disintegration is
      substantiated by respirometric studies, microscopic examination, degree of
      inactivation, and degree of COD release.

PMID- 15575301
TI  - Adsorption of aromatic compounds from water by treated carbon materials.
AB  - Carbon materials with different textural and surface chemistry properties have
      been studied to analyze their behavior in removing aromatic compounds (phenol, o
      chlorophenol, p-nitrophenol, aniline, and phenol compound mixtures) from water. A
      mesoporous high surface area graphite and a microporous activated carbon with
      (HSAGox and ACox) and without (HSAGT and ACT) oxygen surface groups, were used as
      adsorbents. Apparent surface areas, surface oxygen groups, and zero points of
      charge have been determined. The adsorption behavior of single compounds on ACT
      depends on the relation between the molecular and the pore sizes. The aniline,
      the nitrophenol, and the chlorophenol interact with the oxygen surface groups of
      oxidized graphite, while there is no evidence of any type of interaction of the
      phenol with these groups. The adsorption of the organic compound mixtures on the
      thermally treated samples is determined by the acid-base character of the
      adsorbate-adsorbent, whereas on the oxidized carbons, the controlling forces are
      the specific interactions between organic molecules and the oxygenated groups.
      Selectivity coefficients for the different mixtures are presented over the entire
      range of adsorption.

PMID- 15575302
TI  - Simultaneous hyperaccumulation of nickel, manganese, and calcium in Alyssum leaf
      trichomes.
AB  - We have developed commercially viable phytoremediation/phytomining technologies
      employing Alyssum Ni-hyperaccumulator species to quantitatively extract Ni from
      soils. The majority of Ni is stored either in Alyssum leaf epidermal cell
      vacuoles or in the basal portions only of the numerous stellate trichomes. Here,
      we report simultaneous and region-specific localization of high levels of Ni, Mn,
      and Ca within Alyssum trichomes as determined by scanning electron
      microscopy/energy-dispersive X-ray analysis (SEM/EDX). Plants were grown in high
      Ni soil, achieving up to 48 400 microg g(-1) Ni in total leaf concentration;
      however, Ca and Mn were not enriched in the experimental soils. The region
      specific localization of hyperaccumulated Ca, Mn, and Ni occurred in three soil
      types, five Alyssum species/ecotypes, and over a wide range of soil Ni
      concentrations. The metal concentration in the trichome basal compartment was
      approximately 15-20% dry weight, the highest ever reported for healthy vascular
      plant tissue.

PMID- 15575303
TI  - Development of a mercury transformation model in coal combustion flue gas.
AB  - A bench-scale entrained-flow reactor was used to extract flue gas produced by
      burning a subbituminous Belle Ayr coal in a 580-MJ/h combustion system. The
      reactor was operated at 400 degrees, 275 degrees, and 150 degrees C with a flow
      rate corresponding to residence times of 0-7 s. Transformations of elemental
      mercury (Hg0) and total gas mercury (Hg(gas)) in the reactor were evaluated as
      functions of temperature and residence time. The most significant mercury
      transformations (Hg0 to Hg(p) and Hg0 to Hg2+) occurred at 150 degrees C, while
      virtually no obvious mercury transformations were observed at 275 degrees and 400
      degrees C. Approximately 30% of total mercury has been oxidized at temperatures
      higher than 400 degrees C. A mass transfer-capacity limit model was developed to
      quantify in-flight mercury sorption on fly ash in flue gas at different
      temperatures. A more sophisticated model was developed to demonstrate not only
      the temperature and residence time effects but also to consider the effective
      surface area of fly ash and dependence of mercury vapor concentration on mercury
      transformations in flue gas. The reaction orders were 0.02 and 0.55 for Hg0 and
      Hg(gas), respectively. Only a few percent of the total surface area of the fly
      ash, in the range of 1%-3%, can effectively adsorb mercury vapor.

PMID- 15575304
TI  - Continuous electricity generation from domestic wastewater and organic substrates
      in a flat plate microbial fuel cell.
AB  - A microbial fuel cell (MFC) is a device that converts organic matter to
      electricity using microorganisms as the biocatalyst. Most MFCs contain two
      electrodes separated into one or two chambers that are operated as a completely
      mixed reactor. In this study, a flat plate MFC (FPMFC) was designed to operate as
      a plug flow reactor (no mixing) using a combined electrode/proton exchange
      membrane (PEM) system. The reactor consisted of a single channel formed between
      two nonconductive plates that were separated into two halves by the electrode/PEM
      assembly. Each electrode was placed on an opposite side of the PEM, with the
      anode facing the chamber containing the liquid phase and the cathode facing a
      chamber containing only air. Electricity generation using the FPMFC was examined
      by continuously feeding a solution containing wastewater, or a specific
      substrate, into the anode chamber. The system was initially acclimated for 1
      month using domestic wastewater orwastewater enriched with a specific substrate
      such as acetate. Average power density using only domestic wastewater was 72+/-1
      mW/m2 at a liquid flow rate of 0.39 mL/min [42% COD (chemical oxygen demand)
      removal, 1.1 h HRT (hydraulic retention time)]. At a longer HRT = 4.0 h, there
      was 79% COD removal and an average power density of 43+/-1 mW/m2. Power output
      was found to be a function of wastewater strength according to a Monod-type
      relationship, with a half-saturation constant of Ks = 461 or 719 mg COD/L. Power
      generation was sustained at high rates with several organic substrates (all at
      approximately 1000 mg COD/L), including glucose (212+/-2 mW/ m2), acetate (286+/
      3 mW/m2), butyrate (220+/-1 mW/ m2), dextran (150+/-1 mW/m2), and starch (242+/-3
      mW/ m2). These results demonstrate the versatility of power generation in a MFC
      with a variety of organic substrates and show that power can be generated at a
      high rate in a continuous flow reactor system.

PMID- 15575305
TI  - Framework for evaluating the "greenness" of chemical processes: case studies for
      a novel VOC recovery technology.
AB  - A system of metrics is proposed for a rough-guide evaluation of the greenness of
      new and existing chemical technologies as well as for the analysis of flow sheets
      of new processes. The proposed methodology is based on a hierarchical approach.
      The main feature of the proposed system is the reflection of the stakeholder
      relevance of various aspects of green chemistry at different levels of the
      hierarchy and the corresponding system boundaries. Therefore, the developed
      methodology provides a basis for the multiobjective comparison of alternative
      technologies in terms of their greenness. A novel technology for recovery of
      volatile organic chemicals (VOCs) using monolithic adsorbents has been evaluated
      in terms of its environmental efficiency using a small set of indicators
      assembled into a hierarchical metric. A comparison between incineration and
      recovery of VOCs via adsorption has been performed using the proposed
      methodology. The comparison highlights considerable environmental advantages of
      the recovery technology. Flow sheet analysis points out which stages of the
      adsorption process could be further improved. Indicators have been evaluated
      within defined system boundaries.

PMID- 15575306
TI  - Protein Z: "light and shade" of a new thrombotic factor.
AB  - Protein Z is a vitamin K-dependent plasma protein described in its human form in
      1984. The amino acid sequence of protein Z shows wide homology with many
      coagulation factors, such as VII, IX, X, and protein C. However, in contrast to
      other vitamin K-dependent coagulation factors, protein Z is not a serine protease
      because of the lack of the active centre in its amino acid sequence. The
      physiological function of protein Z has been uncertain for many years. In vitro
      and in vivo studies recently suggested that protein Z plays an important role in
      inhibiting coagulation, as it serves as cofactor for the inactivation of
      activated factor X by forming a complex with the plasma protein Z-dependent
      protease inhibitor. The role of alterations of the protein Z levels has been
      evaluated in different disease states, with conflicting findings. Most of these
      studies were performed on ischemic vascular diseases. Recently, the possible role
      of protein Z deficiency in the occurrence of cardiovascular diseases has been
      evaluated.

PMID- 15575307
TI  - Revisiting antiphospholipid antibodies: from targeting phospholipids to
      phospholipid binding proteins.
AB  - The antiphospholipid syndrome (APS) is a multi-system prothrombotic disorder
      associated with circulating auto-antibodies directed against various phospholipid
      binding proteins. The major clinical manifestations are recurrent arterial or
      venous thrombosis, but due to its heterogeneity, atypical presentations can
      obscure the diagnosis. Decisions regarding when to attribute complications to aPL
      are difficult. The most established tests are lupus anticoagulant (LA) detected
      by clotting assays and anticardiolipin (aCL) detected by ELISA. Although LA and
      aCL assays are clinically useful, these tests do not clearly differentiate
      antibodies with different specificities. Antibodies to beta2GPI are associated
      with thrombosis in the APS. Although these antibodies are detected by aCL assay
      (e.g. beta2GPI-dependent aCL), some aCL are not associated with the syndrome
      (e.g. beta2GPI-independent aCL). Regarding LAs, more studies are needed to
      determine if it is clinically important to differentiate specificities against
      beta2GPI or prothrombin. The role of aPLs in the pathogenesis of thrombosis
      requires further and intensive investigation. If autoantibodies to particular
      phospholipid binding proteins are shown to be associated with different clinical
      presentations or to confer different risks, the availability of more accurate
      diagnostic techniques will be required for the recognition of pathogenic aPLs. By
      now, clinical judgement, careful exclusion of other etiologies and serial aPL
      levels are helpful in this regard.

PMID- 15575308
TI  - Evaluation of recombinant antigens for the measurement of antibodies to
      streptolysin O and streptococcal DNase B on the Beckman Coulter IMMAGE system and
      comparison with a method employing conventional antigens.
AB  - The performance of a newly devised method employing recombinant antigens for the
      determination of antibodies to streptolysin O and DNase B on the Beckman Coulter
      IMMAGE System was compared with a nephelometric assay using conventional
      antigens. Sera from 114 patients with or without evidence of streptococcal
      infection were analysed by the two techniques. The results obtained with the new
      method correlated well with those of the reference test. The sensitivity of a
      combination measurement of antibodies to streptolysin O and DNase B was higher
      than that obtained when measuring each parameter alone. Handling of the tests was
      easier on the Beckman Coulter IMMAGE System. In conclusion, the new test from
      Beckman Coulter for the measurement of antibodies to streptolysin O and DNase B
      performs well and equals measurements using conventional antigens on a
      nephelometer.

PMID- 15575309
TI  - Determination of beta2-microglobulin in biological samples using an
      immunoenzymometric assay (chemiluminescence detection) or an immunoturbidimetric
      assay: comparison with a radioimmunoassay.
AB  - Monitoring beta2-microglobulin (beta2M) in biological fluids has gained
      considerable interest in pathologies such as haematologic malignancies, renal
      diseases, and chronic inflammatory diseases. Due to limitations of the RIA in the
      routine laboratory, we measure beta2M with non-isotopic methods. 189 patients
      suffering from myeloma (n=66), end stage renal failure (n=54) or inflammation
      (n=69) were included in this study. beta2M was determined in serum, urine and
      dialysate using an immunoenzymometric assay with chemiluminescence detection
      [Immulite Diagnostic Products Corporation (DPC), La Garenne Colombes, France] and
      an immunoturbidimetric assay (Olympus, Rungis, France). The data were compared
      with a radioimmunoassay (Immunotech, Marseille, France) taken as a reference.
      Using serum samples, the immunoenzymometric assay with chemiluminescence
      detection and the immunoturbidimetric assay have reliable analytical
      performances. Values obtained with serum samples are highly correlated with the
      radioimmunoassay (DPC/RIA r2=0.84; Olympus/RIA r2=0.94) whatever the type of
      pathology; however an over-estimation which could be related to cross reactivity
      with beta2M fragments was observed with the RIA method as suggested by crossover
      calibration and recovery studies. Values obtained with urinary samples (n=96) are
      closely related to those obtained with the RIA (DPC/RIA r2 = 0.98; Olympus/RIA:
      r2=0.99). Despite the low levels observed in dialysate (n=57) good correlations
      were observed between Olympus vs DPC (r2=0.85). By contrast, the two non-isotope
      methods are poorly related with the RIA method (DPC vs RIA r2=0.47 and Olympus vs
      RIA r2=0.54). In conclusion, the immunoenzymometric assay with chemiluminescence
      detection or the immunoturbidimetric assay could be used in the routine
      laboratory in order to determine beta2M in plasma, urine and dialysate.

PMID- 15575310
TI  - The use of a differential fluorescent staining method to detect bacteriuria.
AB  - BACKGROUND: This report describes a differential staining method which
      distinguishes gram-positive from gram-negative bacteria in fluorescence. Gram
      positive bacteria appear yellow and gram-negative bacteria appear green. MATERIAL
      AND METHODS: The method is based on two fluorochromes, one acting in the
      wavelength of red, i.e. the acridine orange, and another acting in the wavelength
      of green, i.e. the fluorescein, which together form a red/ green system. In this
      report we compared the accuracy of the differential fluorescent staining method
      and the Gram stain in screening for bacteriuria, as detected by conventional
      cultures. RESULTS: A total of 1487 urine samples were tested. 289 cultures were
      positive. 237 specimens grew a single organism at 10(5) and 10(4) CFU/ml. 224
      smears were detected by the differential fluorescent staining method and 162 were
      detected by Gram stain. 1198 samples failed to grow organisms at 10(5) and 10(4)
      CFU/ml. 107 smears were falsely positive by the fluorescent staining procedure
      and 289 were falsely positive by the Gram stain. On the basis of the culture
      results, the sensitivity of the differential fluorescent staining method was
      94.5% and that of the Gram stain 68.3%. The specificity of the fluorescent
      staining procedure was 91.6% and that of the Gram stain 75.8%. The positive
      predictive value and the negative predictive value of the fluorescent staining
      method were 67.6% and 98.8%, respectively. Those of the Gram stain were 35.9% and
      92.3%, respectively. CONCLUSIONS: A wide range of microbiological and chemical
      techniques are available to identify bacteria in urine. This fluorescent staining
      method represents a simple, rapid, reliable method with low-running costs. The
      main advantage of this technique is that it enables the microbiologist to exclude
      the presence of bacteria in the urine within a short time after specimen receipt
      and to eliminate a large number of specimens for culture with significant cost
      saving. Another advantage of the method is that it allows to distinguish gram
      positive from gram-negative bacteria in positive slides on the same day the
      sample is obtained. The stained smears were easily interpreted, even when the
      bacterial counts in the specimen were low.

PMID- 15575311
TI  - Diminished response to activated protein C is not correlated with severity of
      peripheral arterial occlusive disease.
AB  - INTRODUCTION: Poor response to activated Protein C (APC) is a well established
      risk factor for venous thromboembolism. More recently, the hypercoagulable state
      which results from diminished response to APC has also been associated with
      arterial thrombosis. Some studies showed a clear association between low response
      to APC with advanced arterial disease, others, however, failed to support these
      data. Thus, there is ongoing dispute about the impact of a hypercoagulable state
      upon progression of atherosclerosis. MATERIAL AND METHODS: We investigated APC
      ratios and the existence of Factor V Leiden in 800 patients with documented
      peripheral arterial occlusive disease (PAD). Clinical symptoms according to
      Fontaine stages II (intermittent claudication), III (rest pain) and IV (gangrene)
      and the ankle/brachial index served as parameters for the severity of PAD.
      RESULTS: There was no association between low response to APC or existence of
      Factor V Leiden and the clinical stage of PAD or ankle/ brachial index.
      CONCLUSION: Our data suggest that poor response to APC is not correlated with the
      severity of peripheral arterial occlusive disease.

PMID- 15575312
TI  - Evaluation of a chemiluminescence immunoassay for the determination of intact
      parathyroid hormone using the ADVIA Centaur.
AB  - We tested a new chemiluminescence immunoassay for intact parathyroid hormone
      (PTH) (ADVIA Centaur intact PTH-serum assay). It is a two-site sandwich
      immunoassay using direct chemiluminescence technology. We investigated precision
      with serum pools at three levels of the analyte, analyzed in duplicate for 12
      days. Total coefficients of variation (CVs) were between 4.6 and 14.4%. The intra
      assay precision was between 4.4 and 6.1%. Day-to-day reproducibility was between
      1.5 and 13.1% for pools with a PTH concentration between 10 pg/ml and 70 pg/ml
      (about 1 to 7 pmol/l). The analytical sensitivity was 3.1 pg/ml. The functional
      sensitivity did not differ from 3 SD minimal detectable concentration (MDC). The
      linearity was good in the range from 3.1-1930 pg/ml. Comparison with the IRMA
      used in our laboratory was analyzed by Passing-Bablok and Bland-Altman plots and
      revealed a proportional bias of +/-60% (slope: 1.58; IC: 1.53 to 1.63) and a
      systematic bias of -3.3 pg/ml which should not have any clinical consequence in
      the interpretation of the results. We established a reference range based on our
      hospital population. We evaluated 87 subjects without abnormality of calcium
      metabolism and with normal vitamin D supply. Three groups of patients were also
      analyzed: 57 patients with vitamin D insufficiency, 17 with renal failure and 15
      with hypercalcemia (7 due to primary hyperparathyroidism and 8 due to another
      etiology). Reference ranges were from 10.2 to 93 pg/ml for CLIA measurement and
      from 6.4 to 68 pg/ml for IRMA measurement. PTH values measured by CLIA varied
      from 6 to 142 pg/ml in patients with vitamin D insufficiency. By CLIA
      measurement, intact PTH was between 26 and 892 pg/ml in renal failure, between 54
      and 201 pg/ml in primary hyperparathyroidism and between 0 and 29 pg/ml in
      patients with another etiology of hypercalcemia. The results of PTH measurements
      in EDTA plasma did not differ significantly from those performed in serum
      (Passing Bablock).

PMID- 15575313
TI  - Serum levels of nitric oxide end products and interactions with lipoproteins in
      patients with coronary artery disease.
AB  - The purpose of this study was to examine whether the serum levels of nitric oxide
      end products and the ratio of nitrite to lipoproteins are valid instruments in
      the clinical follow-up of patients with coronary artery disease. 65 subjects were
      divided into three groups, including patients with coronary artery disease,
      silent coronary artery disease and controls. The serum nitrite level and also the
      ratio of nitrite to high-density lipoprotein were significantly different between
      the groups. According to the number of obstructed arteries, the serum nitrite
      level and the ratio of nitrite to high-density lipoprotein were found
      statistically different between the groups. There was a positive correlation
      between the serum nitrite level and the ratio of nitrite to high-density
      lipoprotein and the number of obstructed arteries. In conclusion, the serum
      nitrite level and ratio of nitrite to high-density lipoprotein may provide a
      beneficial guide to follow-up the status of patients with coronary artery
      disease.

PMID- 15575314
TI  - Regulating forensic deviance: the ethical responsibilities of expert report
      writers and witnesses.

PMID- 15575315
TI  - Polygraphy evidence: a temporary setback or closure?

PMID- 15575316
TI  - Multiple child deaths: a new direction in death notification.

PMID- 15575317
TI  - Failure to warn of allergic reaction to CT contrast agent--breach of duty--no
      therapeutic privilege-causation. Di Carlo v Dubois.

PMID- 15575318
TI  - Defamation--defences--fair protected report of court proceedings. Rogers v
      Nationwide News Pty Ltd.

PMID- 15575319
TI  - Quarantine in times of emergency: the scope of s 51(ix) of the Constitution.
AB  - This article explores the scope of s 51(ix) of the Constitution, the power of the
      Commonwealth to make laws with respect to "quarantine". While this power has
      sustained the Quarantine Act without a challenge since 1908, it may be that
      future national public health emergencies, such as epidemics or bioterrorism,
      will (as has happened in other countries) demand a level of federal preparedness
      that requires augmented public health powers at a national level. If so, will the
      scope of the quarantine power, as determined by the High Court, be wide enough
      allow the Commonwealth to implement these powers? While there is some advantage
      in a national approach, there is also some authority suggesting that the
      quarantine power could not extend to domestic public health controls. If there is
      uncertainty about the scope of the power, what are the options? Should there be
      another approach, with the States, Territories and the Commonwealth moving
      towards uniform legislation and co-operative arrangements?

PMID- 15575320
TI  - Litigation and the medical indemnity crisis.
AB  - The medical indemnity crisis in Australia forced doctors, lawyers and insurers to
      re-appraise the way they handle claims for compensation for medical error. This
      article examines some of the new approaches available in Australia when patients
      claim compensation from their doctors.

PMID- 15575321
TI  - Stem cell technologies: regulation, patents and problems.
AB  - Human embryonic stem cell research promises to deliver in the future a whole
      range of therapeutic treatments, but currently governments in different
      jurisdictions must try to regulate this burgeoning area. Part of the problem has
      been, and continues to be, polarised community opinion on the use of human
      embryonic stem cells for research. This article compares the approaches of the
      Australian, United Kingdom and United States governments in regulating human
      embryonic stem cell research. To date, these governments have approached the
      issue through implementing legislation or policy to control research. Similarly,
      the three jurisdictions have viewed the patentability of human embryonic stem
      cell technologies in their own ways with different policies being adopted by the
      three patent offices. This article examines these different approaches and
      discusses the inevitable concerns that have been raised due to the lack of a
      universal approach in relation to the regulation of research; the patenting of
      stem cell technologies; and the effects patents granted are having on further
      human embryonic stem cell research.

PMID- 15575322
TI  - Surrogacy: is there a case for legal prohibition?
AB  - Surrogacy arrangements are a complex and challenging issue for legal regulation.
      On the one hand, if we wish to promote personal autonomy and enable the infertile
      to experience parenthood, there is a case for allowing these arrangements to
      proceed. However, objections to legal sanctioning of surrogacy include concerns
      for the surrogate and the child born through the surrogacy arrangement. Legally
      sanctioning surrogacy may also adversely affect social conceptions of women's
      roles or may be considered a form of commodifying women's reproductive
      capacities. This article examines these challenges to allowing surrogacy, but
      concludes that surrogacy should not be legally prohibited.

PMID- 15575323
TI  - Oregon: does physician-assisted suicide work?
AB  - Since November 1997, Oregon, a State in the United States of approximately 3.3
      million people, has allowed physician-assisted suicide, although not euthanasia,
      by virtue of the Death with Dignity Act. Before the Act, physician-assisted
      suicide, as in Australia and other common law jurisdictions, was illegal. Under
      the Act, the Oregon Department of Human Services is required to collect
      information and provide an annual report. The Sixth Annual Report on Oregon's
      Death with Dignity Act was released on 10 March 2004.

PMID- 15575324
TI  - The construction of socially remedial legislation in Australia: the strange case
      of hydrotherapy.
AB  - The article examines the canons of construction of socially remedial statutes in
      Australia and the utility and acceptance of hydrotherapy as a means of medical
      treatment. It considers cases from various administrative bodies in Australia as
      they have applied to this mode of treatment and notes that the canons have not
      been applied uniformly. The results have sometimes been unhappy. The article
      suggests why that might be the case and argues that the process may have
      undermined the medical utility of the treatment.

PMID- 15575325
TI  - Duty to warn of genetic harm in breach of patient confidentiality.
AB  - Harm caused by the failure of health professionals to warn an at-risk genetic
      relative of her or his risk is genetic harm. Genetic harm should be approached
      using the usual principles of negligence. When these principles are applied, it
      is shown that (a) genetic harm is foreseeable; (b) the salient features of
      vulnerability, the health professional's knowledge of the risk to the genetic
      relative and the determinancy of the affected class and individual result in a
      duty of care being owed to the genetic relative; (c) the standard of care
      required to fulfil the duty to warn should be the expectations of a reasonable
      person in the position of the relative; and (d) causation is satisfied as the
      harm is caused by the failure of intervention of the health professional.
      Legislation enacted subsequent to the Report of the Commonwealth of Australia,
      Panel of Eminent Persons (Chair D Ipp), Review of the Law of Negligence Report
      (2002) and relevant to a duty to warn of genetic harm is considered. The modes of
      regulation and penalties for breach of any future duty to warn of genetic harm
      are considered.

PMID- 15575326
TI  - Merkel cell carcinoma of the cheek with metastases to the parotid gland: a report
      of two cases.
AB  - Merkel cell carcinoma (MCC) is a rare tumor of neuroendocrine origin. It is a
      highly invasive and aggressive neoplasia, that frequently presents regional and
      distant metatases. Therefore, there is high mortality associated with it. This
      report presents two male patients, one sixty three years and the other eighty
      eight years of age, with MCC of the cheek and invasive metastatic lesions to the
      head and neck areas. One of the patients died of associated distant metastatic
      disease and the other patient died of comorbid conditions present at time of
      tumor excision.

PMID- 15575327
TI  - Kyphoplasty for the management of osteoporotic and malignant fractures of the
      spine.

PMID- 15575328
TI  - The surgical management of insulinoma.
AB  - Insulinoma is the most common endocrine tumor of the pancreas. Over 90% of the
      insulinomas are benign and single, and can be cured by simple excision. Depending
      on the location, insulinomas can be enucleated, might require partial or distal
      pancreatectomy or pancreaticoduodenectomy. Five cases with insulinoma
      successfully treated by surgical intervention, two by enuclation, two by distal
      pancreatectomy and splenectomy, and preservation of the spleen have been
      summarized. The management of insulinoma involves the diagnosis, localization of
      the tumor and treatment. Insulinomas are rare tumors of the pancreas.
      Nevertheless, it is the most common endocrine tumor of the pancreas. Specifically
      arising from the beta cells, of the islets of Langerham, that produce insulin
      (fig.1). Its incidence is one in 250,000 inhabitants. It can be seen at any age,
      but is more frequent in females between 4 and 82 years of age, with a mean of
      45.5 years. Insulinomas are evenly distributed between the head, body and tail of
      the pancreas. Over 90% are benign and single and can be cured by simple excision.
      Depending on the location insulinomas can be enucleated, might require partial or
      distal pancreatectomy or a pancreaticoduodenectomy. Ten percent could be
      malignant when metastasis to peripancreatic lymph nodes or to the liver is
      detected. The course of the patient with malignant insulinoma is an indolent one.
      The release of insulin leads to fasting hypoglycemia producing confusion, loss of
      consciousness, coma or convulsions. The hypoglycemia in turn can induce the
      release of cathecolamines producing tachycardia, tremulousness and diaphoresis.
      The Whipple's triad must be present for the diagnosis of insulinoma; symptoms of
      hypoglycemia, glucose level below 50 mgs/dl and relief of symptoms by the
      administration of glucose. In large series the interval between the onset of
      symptoms and a definitive diagnosis of insulinoma was 37 months, with a range of
      0 to 14 years.

PMID- 15575329
TI  - Office hysteroscopy and suction curettage: a two-year experience at Bayamon Ob
      Gyn office.

PMID- 15575330
TI  - Experience of aortic aneurysms in the Cardiovascular Center of Puerto Rico and
      the Caribbean (1992 through 1997).
AB  - One hundred and nine cases of aortic aneurysm or dissection at the Cardiovascular
      Center of Puerto Rico and the Caribbean, during the period of 18 August 1992 to
      30 September 1997, were reviewed. Twenty seven cases had aortic dissection,
      fourteen type A and eight type B, and five were abdominal. One hundred and seven
      cases were operated on, eighty electively and twenty seven as an emergency; two
      patients refused surgery. As expected, all patients with dissection were
      symptomatic whereas of the others forty four were asymptomatic and thirty eight
      were symptomatic. There were twelve deaths, nine due to hemorrhage and one each
      due to cardiac tamponade, myocardial infarction and ventricular arrhythmia. Most
      of the deaths occurred in patients who had sustained an aortic dissection.

PMID- 15575331
TI  - Commentary on malpractice, history and the surgeon.

PMID- 15575332
TI  - [David Rodriguez Perez, MD].

PMID- 15575333
TI  - [Juan Pantaleon Aviles].

PMID- 15575334
TI  - The laboratory versus the natural environment.

PMID- 15575335
TI  - Effect of release time on preferred gain and speech acoustics.
AB  - Eighteen experienced hearing aid users with mild to moderate sensorineural
      hearing loss were fit with a digital hearing instrument. An adaptive procedure
      was used to determine their preferred gain setting for continuous speech under
      six conditions. Release time (RT) was set to 40, 160, or 640 msec. A prerecorded
      speech stimulus was presented in quiet or in the presence of multitalker babble
      (10 dB signal-to-babble ratio); all other compression variables were fixed. Real
      ear data obtained with settings for each condition suggest that RT did not affect
      gain preference; however, subjects preferred higher gain in the presence of the
      multitalker babble. The RMS amplitudes of 30 phonemic units were calculated using
      ear canal recordings of the speech stimulus for each subject in each condition.
      Altering RT resulted primarily in decreased amplitude with increased RT, but this
      effect was not predictable across listeners or conditions.

PMID- 15575336
TI  - Effects of identification technique, extraction method, and stimulus type on
      mismatch negativity in adults and children.
AB  - The overall aims of the study were to determine optimal methods and stimuli for
      eliciting mismatch negativity (MMN), extracting MMN from the deviant and standard
      waveforms, and identifying the response in children and adults. Several stimulus
      types were compared (pure tones, chords, and natural speech tokens) to determine
      which optimally elicit MMN. Deviant-alone and flip-flop MMN extraction methods
      that control for stimulus effects on MMN were compared for the speech stimuli
      (/da/ and /ga/). Visual identification, an area criterion, and integral
      distribution techniques were used to identify MMN. Eight adults (20 to 28 years)
      and eight children (8 to 12 years) participated in the study. The deviant-alone
      method elicited bigger MMN area and duration than the flip-flop method for the
      speech stimuli. An area criterion of 110 microV x msec identified 90% of visually
      identified MMN compared to 62% identified using the integral-distribution
      technique. For both children and adults, speech stimuli and one of the chords
      most consistently elicited MMN.

PMID- 15575337
TI  - Prevalence of central auditory processing (CAP) abnormality in an older
      Australian population: the Blue Mountains Hearing Study.
AB  - Age-related central auditory processing (CAP) abnormality has been described in
      many studies with widely varying prevalence reported. To date, there has been
      only one population study to report prevalence for this age-related condition,
      and these rates were significantly lower than in reports from clinical studies.
      The present study reports findings from a recent population study in which 2015
      Australians aged 55 years and older living in a defined area west of Sydney were
      assessed with a battery of behavioral and electrophysiological auditory tests.
      This battery included speech measures from which a high overall prevalence rate
      (76.4%) of CAP abnormalities was found, in keeping with previous clinical
      studies. While gender differences were dependent on the test measure, the number
      of abnormal test outcomes increased systematically with age. Hearing loss and
      abnormal cognitive function, however, did not systematically increase with number
      of abnormal test outcomes.

PMID- 15575338
TI  - Averaged electrode voltage testing to diagnose an unusual cochlear implant
      internal device failure.
AB  - This paper describes an unusual Clarion 1.2 cochlear implant failure in order to
      demonstrate the need for the clinical availability of electrode voltage testing.
      The case report describes a patient with a Clarion 1.2 cochlear implant who
      exhibited poor auditory progress in spite of grossly normal impedances and
      electric field testing, and an appropriate educational and psychosocial
      environment. For a subset of electrodes, however, electrode voltage testing was
      abnormal. At explantation it was found that the epoxy that protects the
      connection between the electrode leads of the array and the output contacts on
      the internal controller had fractured. This failure was not associated with
      reported head trauma. This case report demonstrates the utility of and clinical
      need for electrode voltage testing as a helpful tool to diagnose internal device
      failure.

PMID- 15575339
TI  - Quantification of directional benefit across different polar response patterns.
AB  - The purpose of this study was to assess the relationship between the directivity
      of a directional microphone hearing aid and listener performance. Hearing aids
      were fit bilaterally to 19 subjects with sensorineural hearing loss, and five
      microphone conditions were assessed: omnidirectional, cardioid, hypercardioid,
      supercardioid, and "monofit," wherein the left hearing aid was set to
      omnidirectional and the right hearing aid to hypercardioid. Speech perception
      performance was assessed using the Hearing in Noise Test (HINT) and the Connected
      Speech Test (CST). Subjects also assessed eight domains of sound quality for
      three stimuli (speech in quiet, speech in noise, and music). A diffuse soundfield
      system composed of eight loudspeakers forming the corners of a cube was used to
      output the background noise for the speech perception tasks and the three stimuli
      used for sound quality judgments. Results indicated that there were no
      significant differences in the HINT or CST performance, or sound quality
      judgments, across the four directional microphone conditions when tested in a
      diffuse field. Of particular interest was the monofit condition: Performance on
      speech perception tests was the same whether one or two directional microphones
      were used.

PMID- 15575340
TI  - Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC
      on endothelial relaxation via affecting oxidizing metabolism in diabetic rats.
AB  - Oxidative stress and dyslipidaemia play an important role in the development of
      diabetes-induced vascular complications. The aim of this study was to examine the
      reversal effects of simvastatin on some metabolic and oxidative parameters, and
      vascular functions in diabetic rats. Diabetes was induced by a single injection
      of streptozotocin (STZ, 45 mg/kg, i.p.). Eight weeks after STZ induction, some of
      the diabetic and control rats were treated with simvastatin (10 mg/kg rat/d) for
      4 weeks. Plasma glucose, triglyceride and total cholesterol concentrations were
      significantly increased in 12-week diabetic rats. Simvastatin treatment stopped
      the loss of body weight, completely normalized the increase of plasma lipids and
      partially reduced the hyperglycaemia in diabetic rats. Increased malondialdehyde
      levels, catalase and glutathione peroxidase activities were normalised by
      simvastatin treatment in diabetic aorta. Phenylephrine (PE)-induced contractility
      in aorta rings was unaffected by diabetes, but was markedly decreased after
      simvastatin treatment in both control and diabetic rats. Reduction of endothelium
      dependent vasorelaxation in diabetes was significantly ameliorated by simvastatin
      treatment. Incubation of aorta rings with lysophosphatidylcholine, a component of
      the oxidized LDL, did not significantly affect PE-induced contractions, but
      reduced endothelium-dependent relaxations more in untreated-diabetic rats than in
      other experimental groups. The endothelium-independent vasorelaxations were
      similar in all ring preparations. These results indicate that simvastatin
      treatment may ameliorate diabetes-induced abnormal vasoconstriction and
      endothelial dysfunction via affecting general and oxidizing metabolism, nitric
      oxide disability and intracellular calcium mobilisation.

PMID- 15575341
TI  - The dual-wave bolus feature in continuous subcutaneous insulin infusion pumps
      controls prolonged post-prandial hyperglycaemia better than standard bolus in
      Type 1 diabetes.
AB  - The dual-wave bolus delivers a combination of an immediate normal pre-meal
      insulin bolus (approximately 3 min) followed by an extended (or square-wave)
      bolus that is evenly delivered over several hr as programmed by the patient. The
      purpose of this study was to compare post-prandial glycaemic excursions following
      a high-fat meal after administration of insulin by normal vs dual-wave bolus.
      During this prospective, cross-over, repeated measures study, subjects with
      diabetes and treated with insulin pump therapy were evaluated using the
      continuous glucose monitoring system (CGMS) following three combinations of meal
      and bolus type. A control meal or a high-fat meal was given in place of the
      evening meal on three separate occasions and comparisons were made between: a)
      the control meal with normal insulin bolus delivery, b) the high-fat meal with
      normal insulin bolus delivery, and c) the high-fat meal with dual-wave insulin
      bolus delivery. Although mean baseline CGMS values were similar in each of the
      three combinations of meal and bolus type (p=0.54) and in the three hr
      immediately following the meal (p=0.64, p=0.83, p=1.0), when compared to the
      control meal/normal bolus and high-fat meal/dual-wave bolus combinations, CGMS
      profiles disclosed significantly elevated post-prandial glucose in hr 5 through
      14 (p<0.05) following the high-fat/normal bolus combination. Prolonged post
      prandial glycaemic excursions are identified using the CGMS. Treating post
      prandial hyperglycaemia with dual-wave insulin delivery may help manage chronic
      hyperglycaemia in patients with diabetes.

PMID- 15575342
TI  - Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E
      supplementation in Type 2 diabetic patients.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular
      risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G
      polymorphism of PAI-1 has been reported to be involved in the incidence of
      cardiovascular disease by regulation of PAI-1 levels, but this relation is still
      under debate. The aim of the study was to test the effect of 4G/5G polymorphism
      on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E
      supplementation. Ninety-three Type 2 diabetic subjects (age +/- SD, 62.1 +/- 6.1
      yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We
      determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5th and
      10th week) and after (30th week) vitamin E supplementation. No significant
      differences were found in PAI-1 and its determinants among the three genotypic
      groups at baseline. Decrements were detected in the whole group in PAI-1 at the
      5th and the 10th week from baseline followed by an increase at the 30th week
      (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with
      respect to those with 5G/5G in PAI-1. In particular, there was a decrease in
      4G/4G and 4G/5G PAI-1 levels from the 10th week, while a decrease in 5G/5G PAI-1
      was observed from the 5th week (p<0.01). The delayed decrease, found in patients
      with at least one 4G allele with respect to those with 5G/5G genotype,
      demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of
      PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects.

PMID- 15575343
TI  - Comparison of metabolic effects of orlistat and sibutramine treatment in Type 2
      diabetic obese patients.
AB  - AIM: The aim of our study was to comparatively evaluate the efficacy and safety
      of orlistat and sibutramine treatment in obese diabetic patients of both sexes,
      with specific attention to metabolic pattern-induced changes and cardiovascular
      effects. METHODS: Patients were enrolled, evaluated, and followed in 3 Italian
      Centres of Internal Medicine. We evaluated 144 obese diabetic patients. All were
      required to have been diagnosed as being diabetic for at least 6 months, and had
      glycaemic control with diet alone or diet and oral hypoglycaemic agents. We
      administered orlistat (360 mg/d) or sibutramine (10 mg/d) in a randomized,
      controlled, double-blind clinical study, and evaluated anthropometric variables,
      glycaemic control, blood pressure and heart rate (HR) during 12 months of this
      treatment. RESULTS: A total of 141 (69 males and 72 females; 35 males and 36
      females, aged 53 +/- 5 yr with orlistat; 34 males and 36 females, aged 51 +/- 4
      yr with sibutramine) completed the 4 weeks on controlled-energy diet and were
      randomized to double-blind treatment with orlistat (n=71) or sibutramine (n=70).
      Significant body mass index (BMI) improvement was present after 6 (p<0.05), 9
      (p<0.02), and 12 (p<0.01) months in both groups. Significant waist circumference
      (WC), hip circumference (HC), and waist/hip ratio (W/H ratio) improvement was
      observed after 12 months (p<0.05, respectively) in both groups. Significant HbA1c
      decrease was obtained after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in
      both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and post
      prandial plasma glucose (PPG) levels were significantly decreased in both groups
      (p<0.05 andp<0.02, respectively). Significant systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) improvement (p<0.05) was present in the orlistat
      group after 12 months. No significant change in blood pressure measurements was
      observed in the sibutramine group during the study. No significant HR variation
      was obtained during the study in either group. Of the 133 patients who completed
      the study, 33.8% of patients in the orlistat group and 13.2% of patients in the
      sibutramine group had side effects (p<0.05 vs orlistat group). Side effect
      profiles were different in the two treatmen groups. All orlistat side effects
      were gastrointestinal events. Sibutramine caused an increase in blood pres sure
      (both SBP and DBP) in one patient, but it was controlled by anti-hypertensive
      treatment. The vita min changes were small and all mean vitamin and beta-carotene
      values stayed within reference ranges. No patients required vitamin
      supplementation. CONCLUSIONS: Both orlistat and sibutramine were effective on
      anthropometric variables and on metabolic pattern during the 12-month treatment;
      in our sample, orlistat appears to be slightly more efficacious as an anti
      obesity drug, while sibutramine intake was not associated to any cardiovascular
      effect and was generally better tolerated than orlistat.

PMID- 15575344
TI  - Prevalence of the metabolic syndrome in a Turkish adult population.
AB  - AIM: The aim of the present study was to determine the prevalence of the
      metabolic syndrome using Adult Treatment Panel III (ATP III) criteria in Adana, a
      southern province of Turkey. METHODS: The randomly selected study population
      included 1637 adults who were 20-79 yr of age. The presence of > or = 3 of
      components like hypertension (defined as blood pressure > or = 130/> or = 85 mmHg
      on two separate examinations, or usage of antihypertensive agents), visceral
      obesity (waist circumference >88 cm in females and >102 cm in men), low HDL
      cholesterol level (<1.04 mmol/l in men and <1.29 mmol/l in females), high
      triglyceride level (a fasting triglyceride level > or = 1.7 mmol/l), fasting
      glucose level > or = 6.1 mmol/l, or usage of antihyperglycaemic drugs, indicated
      the metabolic syndrome. RESULTS: The prevalence of the metabolic syndrome was
      33.4% and more common in women than in men (39.1 vs 23.7%; p<0.0001). Both women
      and men with the metabolic syndrome were older than subjects without. In men,
      frequencies of the metabolic syndrome in urban and rural areas were similar (23.1
      vs 24.3%; p>0.05), but were markedly higher among women in rural than urban areas
      (44.5 vs 31.2%; p<0.0001). CONCLUSIONS: Developing countries like Turkey also
      need to start action to prevent and treat the components of the metabolic
      syndrome. Prevention of the modifiable risk factors, such as obesity and physical
      inactivity, and blood pressure control should be the key strategy for avoiding
      mortality and financial costs of the healthcare system, especially in view of
      limited resources.

PMID- 15575345
TI  - Validation of the Italian version of the WHO-Well-Being Questionnaire (WHO-WBQ)
      and the WHO-Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ).
AB  - AIM: To validate the Italian version of the World Health Organization (WHO)-Well
      Being Questionnaire (WBQ) and the WHO-Diabetes Treatment Satisfaction
      Questionnaire (DTSQ) in Type 1 and Type 2 diabetic patients. METHODS: The
      cultural adaptation of the questionnaires was performed by using standard
      forward/backward techniques. Internal consistency reliability was estimated by
      Cronbach's alpha coefficient. Construct validity was evaluated using the Short
      Form-36 (SF-36) Health Status Questionnaire. Finally, the discriminative
      properties of the questionnaires were evaluated relative to the patients'
      characteristics. The questionnaires were administered to a random sample of
      patients identified in twelve outpatient diabetes clinics. RESULTS: Overall, 412
      subjects were recruited, of whom 96 (23%) with Type 1 diabetes. Item-scale
      correlations were >0.40 for all the items. Cronbach's alpha coefficient was 0.86
      for the WHO-DTSQ and ranged between 0.79 and 0.91 for the WHO-WBQ. High
      correlations were found between WHO-WBQ scales and the mental dimensions of the
      Short Form-36 (SF-36) questionnaire, but not between WHO-DTSQ and SF-36 scores.
      Women, obese subjects, those with longer diabetes duration and multiple
      complications showed a worse quality of life in all of the four areas of the WHO
      WBQ. In Type 2 diabetic subjects, SF-36 scores, but not WHO-WBQ scores, were able
      to discriminate the population according to the treatment modalities. Lower
      levels of treatment satisfaction were related to female gender, longer diabetes
      duration, insulin treatment, presence of diabetes complications and HbA1c levels
      >7.0%. The flexibility of the treatement was perceived as a major problem even
      among patients treated with oral agents. CONCLUSIONS: The WHO-DTSQ can be
      considered as a valuable instrument to be used internationally for the
      description of diabetes treatment satisfaction. The WHO-WBQ also shows adequate
      psychometric properties, but additional data are needed to clarify whether it is
      more sensitive than SF-36, the most widely used generic instrument.

PMID- 15575346
TI  - Expression of cell surface antigens in diabetic patients and healthy controls
      after injury.
AB  - AIMS: Due to the systemic character of Type 2 diabetes, cellular disturbances
      paralleled by an altered expression of various growth factors constitute the
      basis for impaired wound healing. Cell-surface antigens are altered in chronic
      wounds and may also have an effect on the persistance of diabetic foot lesions.
      METHODS: We investigated blood samples of diabetic patients with diabetic foot
      ulcers (n=21) in comparison with those from healthy control patients subsequent
      to an injury (n=9). A blood sample (EDTA) was taken from each participant (in the
      trauma control group on the third day after injury) and examined by flow
      cytometry [fluorescence-activated cell sorter (FACS)]. Typical cell surface
      antigens involved in wound healing were studied [cluster of differentiation
      (CD)2, CD3, CD4, CD25 and human leukocyte antigen (HLA)-diabetic retinopathy
      (DR)]. RESULTS: known to adversely affect wound healing were elevated in diabetic
      patients (CD2 p<0.001; CD3 p=0.016, CD4 p=0.22, CD25 p<0.001). HLA-DR expression
      was also decreased in diabetic foot patients (p=0.023). CONCLUSIONS: Cell-surface
      antigens appear to be altered in diabetic patients when compared to healthy
      controls. Thus, due to the systemic character of Type 2 diabetes, cellular
      disturbances may well constitute the basis for impaired wound healing in
      diabetes.

PMID- 15575347
TI  - Complete relief of pain in acute painful diabetic neuropathy of rapid glycaemic
      control (insulin neuritis) with venlafaxine HCL.
AB  - This article reports a case of a diabetic patient who suffered from acute painful
      diabetic neuropathy, following an intensive insulin treatment after a poor
      glycaemic control period of 8 yr. On the 15th day of the insulin treatment, which
      enabled rapid successful glycaemic control, the patient began complaining of pain
      and a burning sensation in the lower extremities, especially during the night.
      Venlafaxine HCL was initiated and the patient was completely free of pain on the
      third day of the treatment. As insulin neuritis is infrequent among diabetic
      patients we consider it is worth reporting the dramatic effect of the venlafaxine
      HCL treatment.

PMID- 15575348
TI  - Seasonal changes in mortality rates from main causes of death in Japan (1970-
      1999).
AB  - BACKGROUND: It is well recognized that the season of the year exerts an influence
      on some diseases and causes of death such as coronary heart diseases, stroke,
      infectious diseases and so on. METHODS: We evaluated the influence of seasonal
      changes on diseases and causes of death in Japan using the Japan Vital Statistics
      from 1970 to 1999 and recorded weather data (mean temperature), by a Fourier
      decomposition in a log linear regression model. RESULTS: Major influences of
      seasonal change with the highest rates in winter were seen on the following: the
      overall causes of death; infectious and parasitic diseases including
      tuberculosis; respiratory disease, including pneumonia and influenza; heart and
      cerebrovascular diseases; diabetes; and digestive diseases and accidents. Two
      peaks were seen in suicides, a large peak in April and a small peak in autumn.
      Cancer and homicides were little or not at all influenced by seasonality. There
      was no major difference in changes between the years studied, except for
      respiratory disease and tuberculosis, which showed a clear reduction in the
      seasonality effect from 1970 to 1999. CONCLUSIONS: To reduce the overall
      mortality rate and to prolong life expectancy in Japan, measures must be taken to
      reduce those mortality rates associated with seasonal differences, especially
      those causes of death which show a strong correlation with seasonal change:
      respiratory, heart, cerebrovascular, diabetes and infectious diseases.

PMID- 15575349
TI  - Serum carotenoids and vitamins in relation to markers of endothelial function and
      inflammation.
AB  - BACKGROUND: Endothelial cell dysfunction may be related to an increase in
      cellular oxidative stress. Carotenoids and vitamins could have an antioxidant
      mediated tempering influence on endothelial function and inflammation, thereby
      reducing the risk of atherosclerosis. METHODS: We measured serum carotenoids,
      alpha-tocopherol and Vitamin C concentrations in 379 subjects sampled from the
      general population. High-sensitive C-reactive protein (CRP), fibrinogen (Fbg) and
      leukocytes were measured as markers of inflammation. Furthermore, soluble
      intercellular adhesion molecule-1 (sICAM-1) and flow-mediated vasodilation (FMD;
      n= 165) were measured as markers of endothelial function. Relationships between
      serum carotenoids and vitamins and markers of endothelial function and
      inflammation were analysed after adjustment for confounding. RESULTS: In the
      total study group, lutein and lycopene were inversely related to sICAM-1 with
      regression-coefficients of -0.38+/-0.19 (p = 0.04) and -0.16+/-0.08 (p = 0.04)
      per 1 micromol/l, respectively. beta-Carotene was inverse related to leukocytes (
      0.23+/-0.07; p = 0.007) and CRP (-1.09+/-0.30; p = 0.0003) per 1 micromol/l.
      Vitamin C was inverse related to CRP (-0.01+/-0.005; p = 0.04) per 1 micromol/l,
      whereas alpha-tocopherol was positively related to CRP (0.03+/-0.01; p = 0.02)
      per 1 micro/l. Zeaxanthin was inversely related to FMD (31.2+/-15.3; p = 0.04)
      per 1 micromol/l. CONCLUSION: The inverse relations between carotenoids, Vitamin
      C and sICAM-1, CRP and leukocytes may help to explain the possible protective
      effect of carotenoids and Vitamin C on atherosclerosis through an influence on
      inflammatory processes and endothelial function.

PMID- 15575350
TI  - Cardiovascular risk factors in Turkish immigrants with type 2 diabetes mellitus:
      comparison with Dutch patients.
AB  - BACKGROUND: Based on recent epidemiological studies the need for a similar
      approach towards management of cardiovascular risk factors in type 2 diabetics
      with different ethnic background can be questioned. We compared the prevalence of
      cardiovascular risk factors and 10-year absolute risk for a coronary heart
      disease between Turkish and Dutch type 2 diabetes patients. METHODS: A cross
      sectional study was performed using databases from three Dutch studies on type 2
      diabetes, comparing 147 Turkish to 294 Dutch diabetes patients, matched for age
      and gender. Main outcome measures were: total (t-) cholesterol, high-density
      lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL),
      triglyceride, blood pressure, and smoking. The 10-year absolute risk for a
      coronary event was calculated by means of the Framingham risk equation. RESULTS:
      In Turkish diabetics t-cholesterol was lower than in Dutch (5.4 vs. 5.9 mmol/l; p
      < 0.001), in Turkish males HDL was lower than in Dutch male patients (0.94 vs.
      1.08 mmol/l; p = 0.04). The total/HDL-cholesterol ratio in Turkish and Dutch
      diabetics was equal (5.4 vs. 5.4). Less Turkish than Dutch females smoked (9% vs.
      23%; p<0.01). The 10-year absolute risk for a coronary event in both Turkish and
      Dutch male patients was 24%; the risk in Turkish vs. Dutch females was 13% vs.
      15% (not significant). CONCLUSION: The absolute risk for a coronary event in
      Turkish type 2 diabetes patients is similar to the risk in Dutch diabetes
      patients, although important differences in the risk profile exist, in
      particular, the lipid profile and smoking habits differ.

PMID- 15575351
TI  - The association between HLA DQ genetic polymorphism and type 1 diabetes in a case
      parent study conducted in an admixed population.
AB  - Susceptibility to the type 1 diabetes is genetically controlled and there is an
      increased risk associated with the presence of some specific alleles of the human
      leukocyte antigens class II loci (DQA1 and DQB1 genes). The purpose of this study
      is to evaluate the association between type 1 diabetes and HLA DQ alleles using
      case-parents trios in the admixed population of Uruguay composed by a mixture of
      Caucasian, Amerindian and Negroid populations. DQA1 and DQB1 genotyping was
      performed by polimerase chain reaction followed by oligospecific probes
      hybridization in 51 case-parents trios. The transmission disequilibrium test was
      used for detecting differential transmission in the HLA DQ loci. DQB1*0302 was
      the only allele for which preferential transmission is suggested (probability of
      transmission = 67.56%; exact p-value TDT = 0.047 uncorrected for multiple
      comparisons). DQA1*0301 allele showed a trend for preferential transmission
      without achieving statistical significance. This result would confirm the
      hypothesis previously advanced in a case-control study. Therefore, DQB1*0302
      allele could be considered as the most important susceptibility allele for
      developing type 1 diabetes in Uruguay population.

PMID- 15575352
TI  - Hypertonic hyperglycemia progresses to diabetes faster than normotonic
      hyperglycemia.
AB  - To explore whether elevated plasma glucose might progress to diabetes via a
      mechanism that involves plasma hypertonicity, we evaluated the independent and
      joint effects of these variables on diabetes risk. Community-dwelling older
      adults (70+years), who reported no previous diagnosis of diabetes and had glucose
      levels below 200 mg/dl in the 1992 Duke EPESE survey, were re-interviewed in 1996
      for diabetes status (n = 979). Plasma tonicity at baseline was estimated from
      serum glucose, sodium, and potassium measures. In logistic regression models that
      controlled for glucose, as well as age, sex, race, weight status, activity level,
      serum creatinine, history of heart disease, stroke and cancer, plasma
      hypertonicity (> or = 300 mOsm/l) was independently associated with increased
      odds of developing diabetes (OR = 2.0, 95% CI: 0.9-4.2). Hypertonicity magnified
      the effects of elevated glucose (> or = 125 mg/dl), such that individuals with
      both exposures were over four times more likely to develop diabetes than those
      with elevated glucose only (OR = 4.9, 95%CI: 1.7-14.3), adjusting for all
      covariates. When tonicity was replaced by its determinant variables, glucose,
      sodium and potassium, in the multivariable models, independent effects of sodium
      were also observed. Further work is needed to pursue plasma hypertonicity as a
      factor in the progression of elevated plasma glucose to diabetes.

PMID- 15575353
TI  - Childhood infections and risk of wheezing and allergic sensitisation at age 7-8
      years.
AB  - BACKGROUND: Childhood atopic disease has been associated with exposure to
      infections early in life. There is however considerable controversy on this
      issue, since evidence exists for both protective and adverse effects of
      infections. Aim of this study was to investigate the association between
      childhood infections and the occurrence of wheeze and allergic sensitisation in 7
      8-year-old Dutch and German children. METHODS: A nested case-control study was
      conducted among German and Dutch children participating in a large longitudinal
      study on respiratory health. Parents of 510 7-8-year-old children with
      respiratory complaints and an equal number of children without respiratory
      complaints were asked to complete a questionnaire. Blood samples were collected
      for specific serum Immunoglobulin E (IgE) analysis. Data on childhood infections
      were collected through records of the participating Municipal Health Services.
      RESULTS: No association was found between recent wheeze and any of the childhood
      infections investigated. For scarlet fever infection an increased risk of
      allergic sensitisation (OR: 2.82; 95% CI: 1.40-5.72) and sensitisation against
      grasses (OR: 3.00; 95% CI: 1.35-6.69) at the age of 7-8 years was found.
      Varicella infection tended towards increased risk of sensitisation against
      grasses (OR: 1.88; 95% CI: 0.99-3.58). For allergic sensitisation and
      sensitisation against grasses the odds ratios increased with increasing number of
      infections. CONCLUSIONS: The results do not lend support to the suggestion that
      childhood infection protects against wheezing or allergic sensitisation at age 7
      8 years. Scarlet fever or varicella infection presented an increased risk of
      allergic sensitisation.

PMID- 15575354
TI  - Respiratory symptoms and obstructive lung diseases in iron ore miners: report
      from the obstructive lung disease in northern Sweden studies.
AB  - This is a population-based study on the prevalence of respiratory symptoms
      assessed by a mail questionnaire. The objective was to examine if work in an iron
      mine increased the risk of airway symptoms or obstructive diseases. The exposed
      group consisted of 114 previous or current male miners. Referents, 2472 males
      from the province, had never been employed by the mining company or worked as
      miners. Age, smoking and a family history of asthma were considered as possible
      confounders. The miners had an increased risk for respiratory symptoms (OR=2.2,
      95% CI=1.4-3.1) including recurrent wheeze (OR= 2.4, 95% CI= 1.5-3.9),
      longstanding cough (OR= 1.8, 95% CI = 1.0-3.2), and for physician-diagnosed
      chronic bronchitis (OR=2.2, 95% CI= 1.0-4.5). Attacks of shortness of breath and
      asthma manifestations were similar between miners and referents. Higher risks in
      miners were found particularly among the non-smokers for physician-diagnosed
      chronic bronchitis (OR=9.2, 95% CI= 3.0-28) and for symptoms as well. A family
      history of asthma was less common among miners (9.2% vs. 17%, p < 0.05). We
      conclude that miners in a modern underground iron mine had an increased risk of
      respiratory symptoms. In contrast to other studies, this increased risk was
      particularly found in nonsmokers. A family history of asthma may be an important
      confounder in occupational studies of respiratory diseases.

PMID- 15575355
TI  - Cold weather and GP consultations for respiratory conditions by elderly people in
      16 locations in the UK.
AB  - BACKGROUND: Cold weather is associated with increases in mortality and demands on
      hospital services in the UK, particularly by the elderly. Less is known about the
      relationship with patterns of consultation in primary care. We wished to
      determine the magnitude and consistency of associations between cold temperature
      and consultations for respiratory conditions in primary care settings at
      different sites in the UK. METHODS: Time series analysis of any short-term
      effects of temperature on daily general practitioner (GP) consultations made by
      elderly people (65+ years) for lower and upper respiratory tract infections
      (LRTI, URTI) over a 10-year period, 1992--2001. Practices were situated in 16
      urban locations across the UK where a Met Office monitoring station was in
      operation. RESULTS: An association between low temperatures and an increase in
      LRTI consultations was observed in all 16 locations studied. The biggest increase
      was estimated for the Norwich practices for which a 19.0% increase in LRTI
      consultations (95% CI 13.6, 24.7) was associated with every 1 degrees C drop in
      mean temperature below 5 degrees C observed 0-20 days before the day of
      consultation. Slightly weaker relationships were observed in the case of URTI
      consultations. A north/south gradient, with larger temperature effects in the
      north, was in evidence for both LRTI and URTI consultations. CONCLUSIONS: An
      effect that was consistent and generally strongest in populations in the north
      was observed between cold temperature and respiratory consultations. Better
      understanding of the mechanisms by which cold weather is associated with
      increases in consultations for respiratory infections could lead to improved
      strategies for prevention and reduced burdens for health services.

PMID- 15575356
TI  - Left handedness and spine deformities in early adolescence.
AB  - The aim of this study was to investigate the relation between laterality and
      spine deformities in early adolescence, with special reference to sex
      differences. Interviews, anthropometric measurements and clinical examinations of
      body posture were carried out on a sample of 2546 schoolchildren, aged from 11 to
      14 years, in seven elementary schools in the centre of Belgrade. Possible
      confounding factors (age, sex, body weight and body height) were controlled for.
      The overall prevalence of spine deformities (scoliosis and/or thoracic
      hyperkyphosis) in the investigated population was 11.8%, out of which there were
      7.8% adolescents with scoliosis, 4.0% with thoracic hyperkyphosis, and 0.3% with
      both spine deformities. The prevalence of scoliosis was 2.7 times higher in girls
      compared to boys (11.7% vs. 4.3%) while the prevalence of thoracic hyperkyphosis
      was 1,6 higher among boys (5.0% vs. 3.2%). We found 7.6% of the schoolchildren
      examined to be left-handed. Left handedness was significantly related to
      scoliosis in girls (crude OR = 1.60 and 95% confidence interval = 1.01-2.54).
      Multivariate analysis showed that significant independent factors for scoliosis
      were female sex (p < 0.001), age (p = 0.01) and left handedness (p = 0.02). We
      did not find any appreciable relation between left handedness and thoracic
      hyperkyphosis in both sexes.

PMID- 15575357
TI  - Screening of pregnant women for hepatitis B markers in a French Provincial
      University Hospital (Limoges) during 15 years.
AB  - During the 15 years from January 1984 to December 1998 the Limoges University
      Hospital screened 22,859 pregnant patients for hepatitis B surface antigen (HBs
      Ag) and identified 149 positives. The overall prevalence (0.65%) was intermediate
      between prevalences observed among women of French origin (0.29%), French West
      Indies islands (5.68%) and of foreign origin particulary South East Asian origin
      (7.14%) and Sub Saharan African origin (6.52%). Hepatitis B Virus (HBV)
      replication markers was detected with relative low frequence (HBe Ag: 14.4%; HBV
      DNA: 13.7-20%) among HBs Ag positive mothers. Markers of delta hepatitis virus
      was found among 10.5% of the HBs Ag carrier pregnant women. During the 15 years
      study period variations of the global prevalence were not statistically
      significant. Universal prenatal screening and infant immunisation could greatly
      contribute to the control of HBV infection if the polemic about the hepatitis B
      vaccination recently propagated in France will not have a negative effect on the
      acceptance and national programme of vaccination.

PMID- 15575358
TI  - Choosing immunisation coverage indicators at the local level.
AB  - BACKGROUND: The reliability of information sources, as well as the precision of
      coverage indicators are open questions for immunisation coverage surveys.
      METHODS: A sample survey of 323 children from two birth cohorts (1991-1992 and
      1979-1981) was done. The sample was selected from seven health districts out of
      51 in the Lazio region. The information was collected from vaccination cards or
      from parents, using a mail-in questionnaire. We computed three indicators of
      coverage at 24 months of age for polio, diphtheria-tetanus, pertussis (P),
      hepatitis B, and measles (M), depending on the value given to parental recall. We
      also compared up-to-date (UTD) (immunised children at 24 months) and age
      appropriate (months at risk per child) indicators at the local level. RESULTS:
      Response rate was 68.2%. The two birth cohorts were similarly immunised for polio
      (coverage 95%); the younger cohort had higher coverage levels for diphtheria
      tetanus (93% vs. 75%), for P (30% vs. 22%), for M (43% vs. 16%) than the older
      one, even on the basis of parental recall. In the older cohort, diphtheria
      tetanus, P and M coverage levels were 75, 22 and 15%, respectively, on the basis
      of parental recall and 66, 17 and 4% on certification. The age-appropriate
      indicator revealed four districts that completed vaccinations significantly too
      late, while the UTD indicator showed only one district significantly below the
      threshold of 95% of immunized children at 24 months. CONCLUSIONS: Parental recall
      and data from cards are comparable sources, but the former is more sensitive than
      the latter in retrospective studies. Verbal recall should be accepted as
      reasonably reliable in the absence of cards. Age-appropriate indicators give a
      more complete evaluation of the susceptibility in the population, and are more
      precise at the local level.

PMID- 15575359
TI  - Carbon dioxide for euthanasia of laboratory animals.

PMID- 15575360
TI  - In support of your editorial "Considering change".

PMID- 15575361
TI  - Laboratory animal models of temporal lobe epilepsy.
AB  - Temporal lobe epilepsy is a common human disease that is difficult to treat. The
      pathogenesis of temporal lobe epilepsy, which holds many unresolved questions,
      and opportunities for creating more effective treatments and preventative
      strategies are reviewed herein. Laboratory animal models are essential to meet
      these challenges. How models are created, how they compare with each other and
      with the disease in human patients, and how they advance our understanding of
      temporal lobe epilepsy are described.

PMID- 15575362
TI  - Animal models of ischemic stroke: balancing experimental aims and animal care.
AB  - Animal models of ischemic stroke are examples of an induced model that can
      present challenges from the perspectives of protocol review and animal
      management. The review presented here will include a brief summary of the current
      state of knowledge about clinical stroke; a general synopsis of important
      unanswered research questions that justify use of animal stroke models; an
      overview of various animal models of ischemic stroke, including strengths and
      limitations; and a discussion of animal care issues relative to ischemic stroke
      models. Good communication and interactive education among primary investigators,
      laboratory animal veterinarians and caretakers, and institutional animal care and
      use committee members are critical in achieving a balance between research
      objectives and animal care issues when using animal stroke models.

PMID- 15575363
TI  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned model of parkinson's
      disease, with emphasis on mice and nonhuman primates.
AB  - Animal models play a critical role in our understanding of the cause of human
      diseases and provide an opportunity to evaluate new therapeutic treatments. The
      usefulness of an animal model is dependent, in part, on how closely it resembles
      neurochemical, neuropathologic, and behavioral features of the human condition.
      Other considerations that may enhance the value of a model include expense,
      availability, reproducibility, animal morbidity and mortality, and investigator
      experience. Parkinson's disease (PD) is a progressive neurodegenerative disorder
      characterized by slow movements, tremor, and walking impairment due to loss of
      midbrain nigrostriatal neurons and depletion of striatal dopamine. In the PD
      research field, a number of neurotoxic, pharmacologic, and transgenic animal
      models are available for research studies. We will focus on the advantages and
      disadvantages of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned
      mouse and nonhuman primate models of PD. Our goal is to guide researchers in the
      appropriateness of the MPTP models in their studies by balancing understanding of
      the models, objectives of the study, and health and safety of the animals. In
      addition, the technical use and safe handling of MPTP are discussed.

PMID- 15575364
TI  - Lymphoglandular complexes are important colonic sites for immunoglobulin A
      induction against Campylobacter jejuni in a swine disease model.
AB  - Campylobacter jejuni is a common cause of serious food-borne illness. In an
      experimental model of human infection, germfree pigs were given C. jejuni, the
      whipworm Trichuris suis, dual infections with C. jejuni and T. suis, or no
      infection. In dual-infected pigs, a synergistic effect between C. jejuni and T.
      suis was observed 27 days after infection, when T. suis fourth-stage larvae were
      found in the proximal colon. In dual-infected pigs, lymphoglandular complexes
      (LGCs) in the distal colon were substantially enlarged, and C. jejuni was
      detected in cells of the follicle-associated epithelium (FAE) and in cells with
      macrophage morphology within these follicles. In the study reported here, cell
      types in colonic tissues from these pigs were analyzed by use of
      immunohistochemical and morphometric analyses for cell surface markers (IgM, IgG,
      IgA, CD4, CD8, MHC Class II, and macrophage SWC3a). To our knowledge, we provide
      the first description of cell types in mammalian LGCs, document that they have
      all elements necessary for antigen processing, and demonstrate the appearance of
      IgA germinal centers (GC) in LGCs from C. jejuni-infected pigs (single or dual
      infected). Ileocecal Peyer's patches (ICPP) and mesenteric lymph nodes (MLN) also
      had IgA GC development if C. jejuni was present, but LGCs had the greatest amount
      of anti-C. jejuni staining, and appreciable increase in overall follicle size and
      size and number of GCs committed to IgA production. LGCs are present in humans
      and other mammals and are important in other enteric infections.

PMID- 15575365
TI  - Microsatellite analysis in FVB/N mice.
AB  - The purpose of the study reported here was to identify, by size, a set of
      microsatellite markers for use in diagnostic genetic monitoring of FVB/N mouse
      colonies. A large panel of microsatellite markers were chosen on the basis
      oftheir high degree of allelic variability. These markers were then tested for
      their ability to amplify well under a standard set of polymerase chain reaction
      analysis conditions and to present an easily identifiable band on an agarose gel.
      From this panel, we chose at least one marker on each chromosome that amplified
      well under our standard high-throughput conditions. Using this approach, we
      identified the allele sizes for 27 microsatellite markers in the FVB/N strain of
      mice. Each autosomal chromosome and the X chromosome were analyzed using at least
      one locus marker. We have determined a precise size for FVB/N microsatellite
      alleles, as opposed to a description of size in relation to that of a known
      allele.

PMID- 15575366
TI  - Simple duplex fecal PCR assay that allows identification of false-negative
      results in Helicobacter sp.-infected mice.
AB  - We designed a simple and sensitive duplex polymerase chain reaction (PCR) assay
      for detection of false-negative results during routine Helicobacter sp. feces
      analysis. We took advantage of the various Lactobacillus species that form part
      of the normal intestinal flora of laboratory rodents to improve our PCR
      diagnostic assays. Using this one-step PCR assay, we were able to rule out false
      negative results without the need of adding internal standard molecules. This is
      an important quality control for PCR diagnostic tests, since the presence of
      inhibitors in feces can prevent detection of Helicobacter infections using PCR
      analysis. Use of this Lactobacillus group-specific PCR assay can be extended to
      other feces tests used in mouse quality-control programs.

PMID- 15575367
TI  - Involvement of calpain isoforms in retinal degeneration in WBN/Kob rats.
AB  - Results of our recent studies in rats suggested that calpains play an important
      role in retinal cell death induced by ischemia-reperfusion in vivo and by hypoxia
      in vitro. Study of spontaneous animal models could help determine the involvement
      of calpains in human retinopathy. The WBN/Kob rat is such a model for spontaneous
      retinal degeneration. The purpose of the study reported here was to determine the
      involvement of calpain isoforms during retinal degeneration in WBN/Kob rats.
      Histologic and functional retinal degeneration in WBN/Kob rats was observed by
      use of light microscopy and electroretinography, respectively. Proteolysis of
      alpha-spectrin in the retina was detected by use of immunoblot analysis in aging
      WBN/Kob rats. This proteolysis was associated with the increases of retinal
      calcium content and caseinolytic activity for calpains 1 and 2. Expression of
      calpain 1, calpain 2, and calpastatin mRNAs in the retina, as measured by use of
      reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, were only
      slightly up-regulated at 24 weeks of age. In contrast, expression of retina
      specific calpains, such as Rt88, Rt88', and Rt90 mRNA, was markedly down
      regulated at 12 weeks of age. Expression of calpain 10 mRNA in the retina was
      only slightly down-regulated at 12 weeks of age. In contrast to mRNA expression,
      various expression patterns of calpain 10 proteins were observed. Increased
      retinal calcium content, leading to activation of calpains 1 and 2, may be an
      important event in the sequential changes leading to degeneration of the retina
      in WBN/Kob rats. Activated calpain causing proteolysis of alpha-spectrin and
      changes in Rt88, Rt88', Rt90 and calpain 10 may also contribute to retinal
      degeneration.

PMID- 15575368
TI  - Scanning electron microscopy of the infundibulum, ampulla, and eggs of mice.
AB  - The objective of the study reported here was to use scanning electron microscopy
      (SEM) to discover and describe the details of three-dimensional profiles and the
      natural (not surgically disturbed) topography/location of the infundibulum in the
      mouse. It will help new investigators to more quickly identify the infundibulum
      for successful transfer of microinjected eggs through a small opening into the
      oviduct/ampulla of pseudopregnant female mice for producing transgenic mice.
      Results of the study also illustrate the geographic orientation and natural
      topographic features of the ovary, infundibulum, ampulla, oviduct, and uterus.
      The presence of cilia on the surface of the crown foldings in the longitudinal
      section of the infundibular head stained with 1% toluidine blue provided direct
      evidence that evagination of the internal cilia of the infundibulum/oviduct
      results in formation of the infundibular crown. The new observation of the
      narrowing region of the infundibular head after surgical removal of the crown
      also suggests that formation of the infundibular crown may have resulted from the
      "evagination process" of internal cilia of the infundibulum/oviduct surface. The
      results also provide new evidence that the crown, terminal opening, and
      appearance of the left and the right infundibula of the same mouse differ.

PMID- 15575369
TI  - Pathogenicity of Helicobacter rodentium in A/JCr and SCID mice.
AB  - Helicobacter rodentium was first recognized as a potential pathogen when it was
      isolated, along with Helicobacter bilis, from a colony of scid/Trp53 knockout
      mice with diarrhea. Clinical disease in these mice was more severe than that
      previously reported in mice infected with H. bilis alone, thus suggesting that H.
      rodentium contributed to the pathogenesis of enteritis. The purpose of the study
      reported here was to address two questions: is H. rodentium pathogenic in mice,
      and when co-infection with a pathogenic helicobacter occurs, does H. rodentium
      augment disease? To this end, A/JCr and C.B-17/IcrCrl-scidBr mice were inoculated
      with H. rodentium and/or H. hepaticus. Twelve weeks after inoculation, mice were
      euthanized. The cecum and liver were evaluated microscopically for evidence of
      disease. Cecal interferon-inducible protein 10 (IP-10), macrophage inflammatory
      protein 1alpha (MIP-1alpha), interleukin 10 (IL-10), and interferon gamma (IFN
      gamma) mRNA values were measured as an indicator of mucosal immune response.
      Hepatic lesions were not identified in mice mono-infected with H. rodentium;
      likewise, cecal lesion scores were not significantly different from those of
      uninfected controls. With the exception of an increased IL-10 mRNA value in SCID
      mice, mean immune-related gene expression in H. rodentium mono-infected and
      uninfected control mice was not significantly different. In contrast, all mice
      infected with H. hepaticus developed moderate to severe hepatitis, significant
      increase in cecal lesion scores, and increased immune-related gene expression.
      The C.B-17/IcrCrl-scidBr mice co-infected with H. hepaticus and H. rodentium had
      liquid cecal contents and low terminal body weight. Further, compared with mice
      infected with H. hepaticus alone, co-infection was associated with significant
      increases of IL-10, MIP-1alpha, and IP-10 mRNA values in C.B-17/IcrCrl-scidBr and
      IFN-gamma and MIP-1alpha mRNA values in A/JCr mice. These results suggested that
      H. rodentium alone does not cause hepatitis or enteritis in A/JCr or C.B
      17/IcrCrl-scidBr mice; however, co-infection with H. hepaticus and H. rodentium
      was associated with augmented cecal gene expression and clinical manifestation of
      disease in immunodeficient mice.

PMID- 15575370
TI  - Evaluation of liposome-encapsulated oxymorphone hydrochloride in mice after
      splenectomy.
AB  - The use of mice in biomedical research is increasing, largely due to the
      production and use of genetically engineered animals. Providing postoperative
      pain control in mice presents many challenges, and long-acting analgesic
      preparations would be advantageous for this species. A single subcutaneous
      injection of a liposome-encapsulated (LE) preparation of oxymorphone was compared
      with multiple injections of buprenorphine or saline in outbred mice undergoing
      splenectomy. Control groups were given isoflurane alone or isoflurane and an
      injection of LE oxymorphone but did not undergo surgery. The following parameters
      were evaluated for 5 days after surgery and were compared with presurgical
      baseline data for each group: food and water consumption, body weight,
      ethographic score, and voluntary exercise on a running wheel. Ethographic scores
      indicated less postsurgical pain in both groups of mice that received either
      analgesic preparation compared with mice that received only saline. However, mice
      given LE oxymorphone had superior postoperative recovery, as measured by wheel
      running distance and body weight gain, compared with mice given buprenorphine or
      saline. Mice undergoing splenectomy had significant decreases in body weight,
      food and water consumption, voluntary exercise, and other normal behaviors.
      Administration of liposomal oxymorphone at the time of surgery improved
      postsurgical recovery as measured by these parameters compared with multiple
      injections of buprenorphine or saline alone. Administration of LE oxymorphone at
      the time of surgery improved postsurgical recovery, as measured by these
      parameters.

PMID- 15575371
TI  - Improved in vitro fertilization and development by use of modified human tubal
      fluid and applicability of pronucleate embryos for cryopreservation by rapid
      freezing in inbred mice.
AB  - We examined in vitro fertilizability and development of 10 inbred mouse strains
      (C57BL/6J, C57BL/10, C57BL/10.D2/newSn, C57BL/10-Thy1.1, C57BL/10.Br/Sn, C3H/He,
      RFM/Ms, STS/A, BALB/c-nu and C.B-17/Icr), and the viability of frozen-thawed in
      vitro fertilized (IVF) embryos after embryo transfer (ET). In seven strains,
      fertilizability was significantly greater in modified human tubal fluid (mHTF)
      compared with modified Krebs-Ringer's bicarbonate solution (TYH medium). The TYH
      medium supported almost no fertilization in four strains. More than 80% of IVF
      embryos developed to the blastocyst stage by 120 h in potassium-enhanced simplex
      optimization medium (KSOM). Reciprocal fertilization between C57BL/6J and BALB/c
      nu gametes in TYH medium yielded poor fertilization o f BALB/c-nu due to
      spermatozoal deficiencies. Increased concentrations of bovine serum albumin and
      spermatozoa during capacitation and Percoll washing did not drastically affect
      fertilization. The mHTF, but not TYH medium, supported BALB/c-nu spermatozoa
      penetration into the zona pellucida irrespective of capacitation media. In vitro
      fertilized embryos frozen-thawed rapidly were transferred to surrogate mothers at
      the two-cell stage. Compared with that of unfrozen controls, rapid freezing had
      no significant effect on fetus development except in C57BL/10.D2/newSn mice.
      These results suggest that mHTF medium is superior with respect to IVF of inbred
      mice, and that KSOM adequately supports in vitro fertilized embryo development in
      inbred mice. The data also indicate that rapid freezing of pronucleate embryos
      following IVF is suitable for cryopreservation and embryo banking of inbred mice
      and for the production of genetically modified mice.

PMID- 15575372
TI  - Helicobacter bilis-associated hepatitis in outbred mice.
AB  - Although Helicobacter bilis infects mice worldwide, it is not known whether H.
      bilis causes enterohepatic disease in outbred Swiss Webster (SW) mice. Intestinal
      and liver specimens from four groups of 39 SW mice, five of which were treated
      with creatine in the drinking water, were obtained for culture for the presence
      of H. bilis and were analyzed as to whether infection status was associated with
      H. bilis seroconversion and/or hepatitis. Helicobacter bilis was isolated from
      the colon of all 27 mice of groups I-III, but only from the liver of one 12- to
      13-month-old female mouse. Ten of 27 livers were H. bilis-positive based on
      polymerase chain reaction (PCR) analysis; 8 of 10 (80%) of the positive results
      were for older mice. Results of PCR analysis for H. bilis were negative, and H.
      bilis was not isolated from 12 control mice (group IV). Irrespective of treatment
      group or controls, severity of histologic lobular and periportal chronic
      inflammatory lesions in the liver of H. bilis-infected outbred mice ranged from
      minimally to moderately severe. Helicobacter bilis infection was associated with
      increased portal inflammation in group III mice, compared with age-matched,
      helicobacter-free, group IV mice (P < 0.03). A comparison of potential sex
      effects in group III mice indicated that H. bilis-infected female mice developed
      more severe portal inflammation than did H. bilis-infected male mice (P < 0.01).
      On the basis of results of an ELISA, 8 of 11, 6- to 8-month-old H. bilis-infected
      mice of group III seroconverted to H. bilis outer membrane antigen. Helicobacter
      bilis infection is associated with hepatitis in SW mice and can confound
      experimental results.

PMID- 15575373
TI  - Outbreak of Mycobacterium bovis in a conditioned colony of rhesus (Macaca
      mulatta) and cynomolgus (Macaca fascicularis) macaques.
AB  - We describe a tuberculosis outbreak caused by Mycobacterium bovis in a
      conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca
      fascicularis) macaques. Animals in five rooms were exposed, but most (16/27)
      infections were confined to the room that housed a mixed population of cynomolgus
      and rhesus macaques. In this room, rhesus (8/8) and cynomolgus (10/11) macaques
      naturally exposed to M. bovis were infected at nearly identical rates (Fisher
      exact test, 2-tailed P = 1). The clinical signs of disease and pathologic lesions
      in infected macaques, however, were moderately different between the two species.
      Rhesus macaques were more likely (5/8) to exhibit clinical signs of persistent
      coughing and inappetance, and had more severe pulmonary lesions. By contrast,
      clinical signs of disease were seen in only 1 of 19 cynomolgus macaques, and
      overall, the pulmonary lesions were often focal and less severe, although some
      still had severe involvement of the lungs similar to that seen in rhesus
      macaques. These differences should be taken into consideration when developing or
      evaluating a tuberculosis-screening program. On the basis of observations made
      during this outbreak, we recommend that alternative screening methods such as the
      PRIMAGAM test and the ESAT-6 ELISA, be incorporated into the screening program to
      aid in the identification of infected animals.

PMID- 15575374
TI  - Legg-Calve-Perthes disease in a rhesus macaque (Macaca mulatta).
AB  - A juvenile rhesus macaque presented with atrophy of the musculature of its left
      leg. Physical examination localized the problem to the coxofemoral joint.
      Radiography revealed changes consistent with Legg-Calve-Perthes (LCP) disease.
      Femoral head ostectomy was performed, and the femoral head was submitted for
      histologic examination, results of which confirmed a diagnosis of LCP.

PMID- 15575375
TI  - [Expression of p16INK4a in various cancer cells].
AB  - The p16INK4a protein was detected by means of monoclonal antibodies to this
      protein in the cells of some carcinomas: that of the lungs (17 samples), urinary
      bladder (6 samples) and mammary gland (4 samples) as well as in the cells of
      three cell lines from of human uterine cervix carcinoma: SiHa (containing high
      risk HPV genome), C33A and HT3 (both HPV-negative but have RB mutations in RB
      gene). Lung carcinoma samples were very heterogenous by the part of cells
      expressing p16INK4a. High content of this protein was found in all 6 samples of
      transient cell urinary bladder carcinoma and in 1 sample of mammary gland ductal
      carcinoma. Cells of all three cell lines also contained p16INK4a. Thus,
      hyperexpression of this protein is not specific for only HPV-positive cancer of
      the uterine cervix. The protein presence in cancer cells seems to be an indicator
      of gene RB mutation or other disturbances of RB pathway.

PMID- 15575376
TI  - [Proteinkinase MAK-V/Hunk as a possible dianostic and prognostic marker of human
      breast carcinoma].
AB  - We propose a system for detection of overproduction of protein kinase MAK-V/Hunk
      in tumours. MAK-V/ Hunk overproduction is observed in about 50% breast
      carcinomas. Positive staining is obseved in tumour cells only and has mainly
      cytoplasmic characteristics. Increased production of MAK-V/Hunk does not
      correlate with histological type of carcinoma, metastasizing, steroid receptor
      status (estrogen and progesterone), proliferative activity. Tumours positive for
      MAK-V/ Hunk were more frequently observed in c-erbB2-positive (3+) tumours than
      in c-erbB2-negative ones. Overproduction of MAK-V/Hunk in human breast cancer may
      be used fore more precise molecular typing of this tumour, in particular in case
      of c-erbB2-positive tumors, however, diagnostic-prognostic value of this new
      molecular marker needs further studies.

PMID- 15575377
TI  - [Expression of estrogen and progesterone receptors and HER-2 by breast cancer
      cells].
AB  - Breast cell carcinomas removed from 62 women aged from 33 to 74 years were
      studied immunohistochemically. 24 tumours were of T1N0M0, 5-T1N1M0, 20-T2N0M0, 11
      T2N1M0 and 2-T2N0M0. Invasive ductal carcinoma occurred in 59.6%, invasive ductal
      in 40.4%. Estrogen receptor expression was found in 59.6%, progesterone in 38.7%.
      Simultaneous expression of these receptors was in 35.5%. Estrogen receptor and
      progesterone receptor expression were registered in 24.2 and 3.2% cases,
      respectively. There was neither estrogen nor progesterone expression in 37%. HER
      2 expression was observed in 45.2%, the highest being at the age from 50 to 55
      years and in invasive ductal carcinoma. Enhancement of estrogen receptor
      expression was accompanied with lower rate of HER-2 expression. All three
      antigens expression does not depend on the presence or absence of metastases to
      the regional lymph nodes.

PMID- 15575378
TI  - [Quantitative analysis of morphological manifestations of cholesterosis and
      concomitant pathology of the gall bladder].
AB  - Morphological study of 345 cholecytectomies revealed gall bladder cholesterosis
      in 173 cases. Network form of cholesterosis was most frequent (73.8%), polyposis
      network was in 18.5% and only 8.7% polypoid form of cholesterosis was found. The
      frequency was similar in males and females, the polypoid form prevailed in males,
      reticular form in females. Main site of cholesterosis was the gall bladder body.
      Combination of cholesterosis with cholelithiasis was in 151 cases (87.3%),
      adenomyomatosis occurred in 33 patients (19%). Cholesterol polyps were found in
      47 patients, in 30 of them they were multiple. The size of cholesterol polyps
      varied from 2 to 17 mm. For the first time mixed glandual-cholesterol polyps are
      described. Morphological picture of xanthogranulomatous cholecystitis was in 7
      patients. The morphological difference between foam and xanthome cells is
      presented.

PMID- 15575379
TI  - [Pathomorphology of West Nile fever].
AB  - 8 patients, aged from 61 to 70 years, died from serous meningoencephalitis during
      the outburst of the West Nile fever in Volgograd in 1999-2001, were studied
      morphologically. Serous meningoencephalitis with necrotic vasculitis is a
      characteristic feature of this fever with degenerative changes and destructive
      foci in the brain. Proteinic and fatty inflammatory and lymphomacrophageal
      reactions were observed in the liver, serous productive myocarditis and
      cardiomyocytic necrosis dystrophy. Desquamative pneumonia, intracapillary
      nephritis were also seen. Immunohistochemical reaction against virus of this
      fever was positive in the vascular endothelium of parenchymal organs,
      hepatocytes, neurons of the brain.

PMID- 15575380
TI  - [Morphological alterations of the rat myocardium in chronic morphine
      intoxication].
AB  - Morphine was administered intraperitoneally to Wistar rats at increasing doses
      from 10 to 60 mg pay during 8 days. Cardiomyocyte damage in the form of
      myocytolysis and wave-like deformations of muscle fibers prevailed at the level
      of light microscopy. Microcirculatory alterations were characteristic: stasis,
      sludge-phenomenon, perivascular and interstitial oedema, diapedes hemorrhages,
      focal proliferation of vascular wall cells. Ultrastructural lesions were as
      follows: subsarcolemma edema, mitochondrial destruction, formation of giant forms
      of mitochondria, single contractures, increasing micropinocytosis, intestitial
      edema.

PMID- 15575381
TI  - [Morphofunctional placental characteristics in pregnant women with chronic
      pyelonephritis and urogenital chlamydia infection].
AB  - Morphological features of the placenta were studied in women with chronic
      pyelonephritis and urogenital chlamydial infection. There was an appreciable
      amount of chaotic sclerotic villi and symplastic nephroses reflecting
      compensatory-adaptive processes. Morphometric study of the afterbirths has shown
      that placenta affected with urogenital infection has large area of the
      intervillous space and small area of chorionic villi involved in gas exchange,
      supply of nutrients and other components to the fetus.

PMID- 15575382
TI  - [Morphofunctional characteristics of the placenta, placental bed and myometrium
      in abnormal labor activity].
AB  - By comparison of dopplerometry results of right uterine artery and umbilical
      cords of a fetus with the histologic and morpho-stereometric data studies of the
      placenta, and also placental bed and myometrium in an operational material at
      Cesarian sections, a morphological basis of disturbances of communications in a
      functional system "mother-placenta-fetus" in hypotonic and hypertonic dysfunction
      of the uterus is revealed. The morphological picture of chronic placental
      insufficiency of the fetoplacentary form in the presence of pathological chorion
      immaturity is revealed in the development of weakness of activity. The
      uteroplacentary form of chronic placentaly insufficiency, incomplete gestation
      reorganization MPA and reduction morphometric parameters of a vascular channel
      miometrium documented formed discoordination of uterine muscles at child birth.

PMID- 15575383
TI  - [Structural characteristics of tubal pregnancy].
AB  - Morphological and immunohistochemical analysis of fallopian pregnancy is
      performed. Structural features of cytotrophoblastic invasion in both types of
      pregnancy are without principal differences. Immunohistochemically low level of
      estrogen and progesteron receptors in the uterine tube as compared to the uterus
      is established. Decidual reaction in a tube pregnancy is not developed in the
      majority of cases this could be a reason of a limitless invasion of
      cytotrophoblast and hemosalpinx development.

PMID- 15575384
TI  - [Argyrophilic proteins of nucleolar organizers regions as markers of malignancy
      grade of anaplastic large-cell lymphoma and Hodgkin's lymphoma].
AB  - Expression of argyrophilic proteins of nucleolar organizers regions (Ag-NOR
      proteins) was studied in tumor cells from 17 patients with a classic variant of
      anaplastic large-cell lymphoma (ALCL) and 22 patients with Hodgkin's lymphoma
      (HL). Eight cases of p80+ and nine cases of p80-ALCL were studied. HL was
      represented by 13 cases with lymphoid depletion by a reticular type and 9 cases
      with nodular sclerosis with a syncytial growth. Ag-NOR-proteins were identified
      using histochemical method with silver nitrate. The expression of Ag-NOR-proteins
      in tumor cells of ALCL and HL appeared intensive, being highest in ALCL cells, in
      p80+ cells of ALCL there was superexpression. The differences in expression of Ag
      NOR-proteins point to different proliferative activity and growth of the above
      variants of ALCL and HL. The test for Ag-NOR-proteins expression can be
      recommended as an additional tool in differential diagnosis, determination of
      malignancy grade, assesssment of prognosis and sensitivity to chemotherapy.

PMID- 15575385
TI  - Traditional and new molecular methods for early detection of cervical cancer.
AB  - Disadvantages of the traditional Papanicolaou-method for the cytological
      detection of cervical carcinomas and their precursors can be overcome by the use
      of specific molecular markers for nuclear attypicality. High grade HR-HPV induced
      cervical dysplasia is initiated by deregulated expression of viral oncogenes in
      replicating epithelial stem cells. Here, the E6-E7 gene products gain control of
      cell cycle and mitotic activity first and induce multistep mutagenesis with
      severe genomic instability in successin. The detailed molecular analysis of these
      activities has allowed the development of biomarkers for dysplastic cervical
      cells. The marked over-expression of the cyclin dependent kinase inhibitor
      p16INK4a is regularly observed in HR-HPV induced malignant lesions and indicates
      an active expression of the viral oncogene E7 in dysplastic cells.
      Morphologically, these molecular deregulations are reflected mainly in an altered
      nuclear-cytoplasmic ratio, anisonucleosis, and hyperchromasia. With p16INK4a
      immunostaining--as reported in the literature--dysplastic and atypical cells can
      be easily detected even under low magnification and differentiated by higher
      magnification from occasional positive atrophic or metaplastic cells by their
      atypical nuclear structure. In questionable cases the additional use of
      proliferation markers could eliminate false interpretation. The results with
      these new molecular techniques can by further optimized by applying the ThinPrep
      method for the preparation of the cytological slides to ensure overlying blood,
      mucus or inflammatory cells do not mask atypical cells. With these new methods we
      can expect to lower the rate of false-positive and false-negative cytology tests
      as experienced with the traditional Papanicolaou-method, of not eliminate them
      completely, gaining thereby great advantages for patients and for cost
      efficiency.

PMID- 15575386
TI  - [Stomach MALT-lymphoma with marked plasmocytic differentiation: a variant of
      Mott's cell tumor].
AB  - Stomach MALT-lymphomas have a specific feature of clinical behaviour and
      prognosis, this being reason to differentiate it from others gastric lymphoma's
      variants. 75 cases of gastric MALT-lymphomas having "classical" morphological
      features with polymorphic tumour infiltration. We described the only case of
      MALToma in our series characterised by a strong marker tendency of monoclonal
      plasmocytic differentiation (including plasmoblasts) with 'signet-ring' cells,
      Dutcher and Russel bodies using morphological, histochemical and
      immunohistochemical methods. We suppose this case to be MALT lymphoma with Mot's
      cell differentiation.

PMID- 15575387
TI  - [Primary renal osteosarcoma].
AB  - A rare case of a primary kidney osteosarcoma with fusiform and bone component is
      described in a 38-year-old male.

PMID- 15575388
TI  - [Extraovarian malignant Brenner tumor].
AB  - Extraovarian malignant Brenner tumour in a female of 35. Rapid infiltrating
      growth with the destruction of tumour. All extraovarian tumours described so far
      were benign, located in the mesosalpinx, uterus or vagina. In this case the
      starting point of the tumour was in the vagina wall or in the recto-vaginal
      septum. Histological picture produced difficulties in establishing histogenesis
      of malignancy. The true nature of the tumour was established only
      immunohistochemically.

PMID- 15575389
TI  - [Epitheliod mesothelioma of the atrioventricular node].
AB  - Malignant tumour located in the atrio-ventricular node provoked grave
      disturbances of cardiac rhythm.

PMID- 15575390
TI  - [Tropical malaria with a fatal outcome in the Rostov region].
AB  - Epidemiological data on malaria in the Rostov region are presented. An autopsy
      case of tropical malaria in a 63-year-old man infected in Uganda is described.
      Treatment was ineffective. Postmortem examination found erythrocytic stasis in
      the viscera, shysonts, deposits of hemomelanin.

PMID- 15575391
TI  - [Philosophic basis of the general pathology theory].
AB  - The general human pathology is the theoretic basis of practical medicine. However
      the general theoretical comprehension of pathological process is in growing
      stage. The number of important problems remain unsolved. In this article a
      version of construction of the deductive theory of general pathology is
      presented. The principle of tissue adaptive regeneration is the optimal principle
      of general theory of pathology.

PMID- 15575393
TI  - [The state-of-the-art and development of medical technologies in Russia].

PMID- 15575394
TI  - [Biotechnologies and gene engineering as priority trends in scientific-and
      technological progress].

PMID- 15575395
TI  - [Some unfinished research in blood physiology].

PMID- 15575396
TI  - [A treatment tactic for severe forms of non-specific ulcerous colitis].

PMID- 15575397
TI  - [The legal control in health protection].

PMID- 15575398
TI  - [New approaches to prognostication of relapses of acute gastroduodenal ulcerous
      hemorrhages].

PMID- 15575399
TI  - [Telemedicine in Russia].

PMID- 15575400
TI  - [The membrane-tropic effect of drugs].

PMID- 15575401
TI  - [Pharmacogenetics and modern medicine].

PMID- 15575402
TI  - [Microsurgical autotransplantation of periosteum-cortical tissue complex for the
      treatment of long tube bone pseudoartrosis].

PMID- 15575403
TI  - [The cellular and molecular-genetic aspects of endothelial dysfunction].

PMID- 15575404
TI  - Nonnegative matrix factorization for rapid recovery of constituent spectra in
      magnetic resonance chemical shift imaging of the brain.
AB  - We present an algorithm for blindly recovering constituent source spectra from
      magnetic resonance (MR) chemical shift imaging (CSI) of the human brain. The
      algorithm, which we call constrained nonnegative matrix factorization (cNMF),
      does not enforce independence or sparsity, instead only requiring the source and
      mixing matrices to be nonnegative. It is based on the nonnegative matrix
      factorization (NMF) algorithm, extending it to include a constraint on the
      positivity of the amplitudes of the recovered spectra. This constraint enables
      recovery of physically meaningful spectra even in the presence of noise that
      causes a significant number of the observation amplitudes to be negative. We
      demonstrate and characterize the algorithm's performance using 31P volumetric
      brain data, comparing the results with two different blind source separation
      methods: Bayesian spectral decomposition (BSD) and nonnegative sparse coding
      (NNSC). We then incorporate the cNMF algorithm into a hierarchical decomposition
      framework, showing that it can be used to recover tissue-specific spectra given a
      processing hierarchy that proceeds coarse-to-fine. We demonstrate the
      hierarchical procedure on 1H brain data and conclude that the computational
      efficiency of the algorithm makes it well-suited for use in diagnostic work-up.

PMID- 15575405
TI  - Motion gradient vector flow: an external force for tracking rolling leukocytes
      with shape and size constrained active contours.
AB  - Recording rolling leukocyte velocities from intravital microscopic video imagery
      is a critical task in inflammation research and drug validation. Since manual
      tracking is excessively time consuming, an automated method is desired. This
      paper illustrates an active contour based automated tracking method, where we
      propose a novel external force to guide the active contour that takes the
      hemodynamic flow direction into account. The construction of the proposed force
      field, referred to as motion gradient vector flow (MGVF), is accomplished by
      minimizing an energy functional involving the motion direction, and the image
      gradient magnitude. The tracking experiments demonstrate that MGVF can be used to
      track both slow- and fast-rolling leukocytes, thus extending the capture range of
      previously designed cell tracking techniques.

PMID- 15575406
TI  - Estimation of displacement vectors and strain tensors in elastography using
      angular insonifications.
AB  - In current practice, only one out of three components of the tissue displacement
      vector and one of nine components of the strain tensor are accurately estimated
      and imaged in ultrasound elastography. Since, only the axial component of both
      the displacement and strain are imaged, other important elastic parameters, such
      as shear strains and the Poisson's ratio, also are not imaged. Moreover,
      reconstruction of the Young's modulus would be significantly improved if all
      components of the strain tensor were available. In this paper, we describe a new
      method for estimating all the components of the tissue displacement vector
      following a quasi-static compression. The method uses displacements estimated
      from radiofrequency echo-signals along multiple ultrasound beam insonification
      directions. At each spatial location in the compressed medium, orthogonal tissue
      displacements in both the axial and lateral direction with respect to the
      direction of the applied compression are estimated by curve fitting angular
      displacement vector data calculated for all insonification directions. Following
      displacement estimation in orthogonal directions, components of the corresponding
      normal and shear strain tensors are estimated. Simulation and experimental
      results demonstrate the utility of this technique for the computation of the
      normal and shear strain tensors.

PMID- 15575407
TI  - Vascular segmentation of phase contrast magnetic resonance angiograms based on
      statistical mixture modeling and local phase coherence.
AB  - In this paper, we present an approach to segmenting the brain vasculature in
      phase contrast magnetic resonance angiography (PC-MRA). According to our prior
      work, we can describe the overall probability density function of a PC-MRA speed
      image as either a Maxwell-uniform (MU) or Maxwell-Gaussian-uniform (MGU) mixture
      model. An automatic mechanism based on Kullback-Leibler divergence is proposed
      for selecting between the MGU and MU models given a speed image volume. A
      coherence measure, namely local phase coherence (LPC), which incorporates
      information about the spatial relationships between neighboring flow vectors, is
      defined and shown to be more robust to noise than previously described coherence
      measures. A statistical measure from the speed images and the LPC measure from
      the phase images are combined in a probabilistic framework, based on the maximum
      a posteriori method and Markov random fields, to estimate the posterior
      probabilities of vessel and background for classification. It is shown that
      segmentation based on both measures gives a more accurate segmentation than using
      either speed or flow coherence information alone. The proposed method is tested
      on synthetic, flow phantom and clinical datasets. The results show that the
      method can segment normal vessels and vascular regions with relatively low flow
      rate and low signal-to-noise ratio, e.g., aneurysms and veins.

PMID- 15575408
TI  - F-information measures in medical image registration.
AB  - A measure for registration of medical images that currently draws much attention
      is mutual information. The measure originates from information theory, but has
      been shown to be successful for image registration as well. Information theory,
      however, offers many more measures that may be suitable for image registration.
      These all measure the divergence of the joint distribution of the images' grey
      values from the joint distribution that would have been found had the images been
      completely independent. This paper compares the performance of mutual information
      as a registration measure with that of other F-information measures. The measures
      are applied to rigid registration of positron emission tomography (PET)/magnetic
      resonance (MR) and MR/computed tomography (CT) images, for 35 and 41 image pairs,
      respectively. An accurate gold standard transformation is available for the
      images, based on implanted markers. The registration performance, robustness and
      accuracy of the measures are studied. Some of the measures are shown to perform
      poorly on all aspects. The majority of measures produces results similar to those
      of mutual information. An important finding, however, is that several measures,
      although slightly more difficult to optimize, can potentially yield significantly
      more accurate results than mutual information.

PMID- 15575409
TI  - A quantitative analysis of 3-D coronary modeling from two or more projection
      images.
AB  - A method is introduced to examine the geometrical accuracy of the three
      dimensional (3-D) representation of coronary arteries from multiple (two and
      more) calibrated two-dimensional (2-D) angiographic projections. When involving
      more then two projections, (multiprojection modeling) a novel procedure is
      presented that consists of fully automated centerline and width determination in
      all available projections based on the information provided by the semi-automated
      centerline detection in two initial calibrated projections. The accuracy of the 3
      D coronary modeling approach is determined by a quantitative examination of the 3
      D centerline point position and the 3-D cross sectional area of the reconstructed
      objects. The measurements are based on the analysis of calibrated phantom and
      calibrated coronary 2-D projection data. From this analysis a confidence region
      (alpha degrees approximately equal to [35 degrees - 145 degrees]) for the angular
      distance of two initial projection images is determined for which the modeling
      procedure is sufficiently accurate for the applied system. Within this angular
      border range the centerline position error is less then 0.8 mm, in terms of the
      Euclidean distance to a predefined ground truth. When involving more projections
      using our new procedure, experiments show that when the initial pair of
      projection images has an angular distance in the range alpha degrees
      approximately equal to [35 degrees - 145 degrees], the centerlines in all other
      projections (gamma = 0 degrees - 180 degrees) were indicated very precisely
      without any additional centering procedure. When involving additional projection
      images in the modeling procedure a more realistic shape of the structure can be
      provided. In case of the concave segment, however, the involvement of multiple
      projections does not necessarily provide a more realistic shape of the
      reconstructed structure.

PMID- 15575410
TI  - Assessment of perfusion by dynamic contrast-enhanced imaging using a
      deconvolution approach based on regression and singular value decomposition.
AB  - The assessment of tissue perfusion by dynamic contrast-enhanced (DCE) imaging
      involves a deconvolution process. For analysis of DCE imaging data, we
      implemented a regression approach to select appropriate regularization parameters
      for deconvolution using the standard and generalized singular value decomposition
      methods. Monte Carlo simulation experiments were carried out to study the
      performance and to compare with other existing methods used for deconvolution
      analysis of DCE imaging data. The present approach is found to be robust and
      reliable at the levels of noise commonly encountered in DCE imaging, and for
      different models of the underlying tissue vasculature. The advantages of the
      present method, as compared with previous methods, include its efficiency of
      computation, ability to achieve adequate regularization to reproduce less noisy
      solutions, and that it does not require prior knowledge of the noise condition.
      The proposed method is applied on actual patient study cases with brain tumors
      and ischemic stroke, to illustrate its applicability as a clinical tool for
      diagnosis and assessment of treatment response.

PMID- 15575411
TI  - Efficient calculation of resolution and covariance for penalized-likelihood
      reconstruction in fully 3-D SPECT.
AB  - Resolution and covariance predictors have been derived previously for penalized
      likelihood estimators. These predictors can provide accurate approximations to
      the local resolution properties and covariance functions for tomographic systems
      given a good estimate of the mean measurements. Although these predictors may be
      evaluated iteratively, circulant approximations are often made for practical
      computation times. However, when numerous evaluations are made repeatedly (as in
      penalty design or calculation of variance images), these predictors still require
      large amounts of computing time. In Stayman and Fessler (2000), we discussed
      methods for precomputing a large portion of the predictor for shift-invariant
      system geometries. In this paper, we generalize the efficient procedure discussed
      in Stayman and Fessler (2000) to shift-variant single photon emission computed
      tomography (SPECT) systems. This generalization relies on a new attenuation
      approximation and several observations on the symmetries in SPECT systems. These
      new general procedures apply to both two-dimensional and fully three-dimensional
      (3-D) SPECT models, that may be either precomputed and stored, or written in
      procedural form. We demonstrate the high accuracy of the predictions based on
      these methods using a simulated anthropomorphic phantom and fully 3-D SPECT
      system. The evaluation of these predictors requires significantly less
      computation time than traditional prediction techniques, once the system geometry
      specific precomputations have been made.

PMID- 15575412
TI  - Multimodal registration of retinal images using self organizing maps.
AB  - In this paper, an automatic method for registering multimodal retinal images is
      presented. The method consists of three steps: the vessel centerline detection
      and extraction of bifurcation points only in the reference image, the automatic
      correspondence of bifurcation points in the two images using a novel
      implementation of the self organizing maps and the extraction of the parameters
      of the affine transform using the previously obtained correspondences. The
      proposed registration algorithm was tested on 24 multimodal retinal pairs and the
      obtained results show an advantageous performance in terms of accuracy with
      respect to the manual registration.

PMID- 15575413
TI  - Autism spectrum disorder: screening, diagnosis, and medical evaluation.
AB  - Autism spectrum disorder (ASD) are a group of behaviorally defined
      neurodevelopmental disabilities with core deficits in socialization,
      communication, and behavior, although the presentation can be extremely variable.
      This article describes the core deficits in ASD, as well as the differential
      diagnosis and the more commonly associated comorbid disorders. The importance of
      early diagnosis is emphasized, and screening and assessment tools are reviewed.
      Finally, the role of the pediatric neurologist is discussed with regard to
      specific components of the evaluation, including history, physical examination,
      and ancillary testing.

PMID- 15575414
TI  - The genetics of autism.
AB  - Autism spectrum disorders (ASD) are among the most heritable of all
      neuropsychiatric disorders. Discovery of autism susceptibility genes has been the
      focus of intense research efforts over the last 10 years, and current estimates
      suggest that 10 to 20 different interacting genes are involved. Evidence from
      twin and family studies demonstrates increased risk in family members not only
      for autistic disorder, but also for a milder constellation of similar symptoms
      referred to as the broader phenotype. In addition, several genetic syndromes and
      chromosomal anomalies have been associated with ASD. Large family studies using
      linkage-analysis techniques have demonstrated several chromosomal regions thought
      to harbor genes related to the disorder. Finally, specific candidate genes based
      on function and location have been explored; these studies are reviewed here.

PMID- 15575415
TI  - Imaging data in autism: from structure to malfunction.
AB  - During the last two decades, neuroimaging studies have improved our knowledge of
      brain development and contributed to our understanding of disorders involving the
      developing brain. Differences in cerebral anatomy have been determined in autism
      spectrum disorder (ASD). Morphological studies by magnetic resonance imaging have
      provided evidence of structural differences in ASD compared with the normal
      population. This has enhanced our view of autism as a neurobiological disorder
      corresponding with different stages and events in brain development. Alterations
      in volume of the total brain and specifically the cerebellum, frontal lobe, and
      limbic system have been identified. There appears to be a pattern of increased
      and then decreased rate of brain growth over time. We integrate these
      observations with neurobehavioral findings to provide a developmental hypothesis
      of the pathophysiology of autism.

PMID- 15575416
TI  - Immunizations, immunology, and autism.
AB  - Public fears of rising rates of children being diagnosed with autistic spectrum
      disorders has led to a fear that immunizations, specifically the measles-mumps
      varicella vaccine (MMR), may trigger autism. This article reviews theories of
      immunization as a risk factor for autism, including thimerosal exposure. We also
      review theories of autoimmunity as a predisposing genetic risk in autistic
      patients. We summarize from multiple population-based studies and extensive
      review committee reports that neither immunization nor thimerosal exposure has
      been conclusively linked to autism. Current treatments for autoimmunity in autism
      are reviewed and summarized as being only anecdotally effective, with no
      controlled studies to conclusively determine effectiveness. The goal of this
      article is to allow child neurologists to effectively counsel parents of autistic
      patients about vaccination risks and treatment options in presumed cases of
      autoimmune dysfunction.

PMID- 15575417
TI  - Electroencephalography findings in autism: similarities and differences from
      Landau-Kleffner syndrome.

PMID- 15575418
TI  - Management of hyperactivity and other acting-out problems in patients with autism
      spectrum disorder.
AB  - Hyperactivity/impulsivity, aggression, self injury, and irritability are
      disruptive behaviors that frequently accompany autism spectrum disorders (ASD).
      The psychostimulants and atypical antipsychotics have been used with some success
      to manage hyperactivity, but neither drug group is fully satisfactory and
      clinical response to the stimulants varies. For other disruptive symptoms
      (irritability, aggression, self injury), both older antipsychotics and newer
      atypical antipsychotics have been shown to have helpful effects. Because of
      potential side effects, atypical antipsychotics should ordinarily be preferred
      over older agents. A small group of studies suggests that selective serotonin
      reuptake inhibitors may be helpful in managing symptoms related to aggression,
      self injury, and the like. A small and largely imperfect literature suggests that
      beta blockers, mood stabilizers, and alpha-2 agonists may also have some role for
      treating such symptoms. More research is needed on the management of all of these
      target symptoms, both for new agents (e.g., atomoxetine) and for established
      psychoactive medicines.

PMID- 15575419
TI  - Neurologic treatment strategies in autism: an overview of medical intervention
      strategies.
AB  - Child neurologists are likely to be caring for an increasing number of patients
      with autistic spectrum disorder (ASD). ASD may occur in as many as 1/100 to 1/200
      births. It appears to be a multifactorial disease, with many phenotypes or
      subgroups. No simple treatment is currently approved for curing or managing core
      symptoms of autism. We rationally propose a symptom-based review of what
      treatments may offer relief to specific subtypes of clinical behaviors seen in
      autism. There is a lack of clinically based evidence on which to universally
      recommend a rational clinical algorithm for treatment; we suggest that rational
      pharmacotherapy may offer symptomatic relief to core areas of dysfunction in the
      autistic population. Future research into rational medical treatment options is
      desperately needed.

PMID- 15575420
TI  - Dr. Audrius Plioplys' comparison of survival rates of children in the California
      data base and his own Chicago-area data base.

PMID- 15575421
TI  - [The case of Vioxx requires consideration].

PMID- 15575422
TI  - [Acetylsalicylic acid resistance--clinical diagnosis with unclear mechanism].
AB  - A review on the subject of aspirin resistance and its role in vascular diseases
      is presented. Although the clinical diagnosis of aspirin resistance is frequently
      made, little is known about its biochemical background. Only a few follow-up
      studies, with varying design, have dealt with the possible association between an
      aspirin resistant phenotype and clinical outcome in patients with
      atherothrombosis. However, it was recently shown that ibuprofen acts as a
      competitive inhibitor in the blockage of COX-1. This pharmacodynamic interaction
      results in secondary aspirin resistance, which may have clinical significance in
      patients taking both medicines. With the complex nature of vascular diseases in
      mind, it is not surprising that aspirin used as a single preventive strategy
      fails in many cases. At present, there is no clear evidence that treatment
      failure is associated with a particular aspirin resistant phenotype.

PMID- 15575423
TI  - [Check list for safer care in stroke].

PMID- 15575424
TI  - [Brief about sample size].

PMID- 15575425
TI  - [Moderate intensive exercise has a positive effect in rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) often confers disability and increased risk of coronary
      heart disease and premature death. Decreased body functions and psychological
      obstacles in the individual with RA, and health care workers' fear of causing
      short-term and long-term aggravation of the disease, might represent barriers to
      starting and maintaining physical activity. However, there is now good evidence
      for the safety and benefit of moderately intensive exercise for individuals with
      RA. Thus, these people should be recommended, and actively supported in, physical
      activity.

PMID- 15575426
TI  - [Open discussion about male ritual circumcision turned emotions hot. A study of a
      debate in Lakartidningen during the years 1997-2003].

PMID- 15575427
TI  - [Basic investigation of infertility].

PMID- 15575428
TI  - [White coat hypertension: high blood pressure in physician's office, but normal
      otherwise].

PMID- 15575429
TI  - [Cult-related mental disorders should be identified in health services].

PMID- 15575430
TI  - [The problem of forensic psychiatry is the lack of hospital beds].

PMID- 15575431
TI  - [Are there any regional differences when it comes to obstetrical care quality?].

PMID- 15575432
TI  - [Physician's role--a combination of the encounter with the patients and the
      exercise of public authority].

PMID- 15575433
TI  - [It's the patient who suffers when physician's knowledge of drugs is not
      sufficient].

PMID- 15575434
TI  - [Importance of non-graded student case discussions].

PMID- 15575435
TI  - [The significance of talk and the importance of "observing man"].

PMID- 15575436
TI  - [The ADHD debate--the upside-down world!].

PMID- 15575437
TI  - Clinical efficacy of a new manual toothbrush on gingivitis reduction and plaque
      removal.
AB  - PURPOSE: To evaluate the safety and efficacy of a new manual toothbrush by
      comparing plaque removal and gingivitis reduction after 4 weeks of use. METHODS:
      This monadic clinical study included 46 subjects from the Northern New Jersey
      area who reported to the clinical facility for a baseline plaque and gingivitis
      examination after having refrained from all oral hygiene procedures and chewing
      gum for 8 hours, and from eating, drinking, or smoking for 4 hours. The
      population was comprised of healthy adult male and female subjects aged 27-68
      years. Subjects were instructed to brush their teeth for 1 minute, twice a day
      with their assigned toothbrush and a commercially-available fluoride toothpaste
      (Colgate Cavity Protection Great Regular Flavor). After 4 weeks of use, subjects
      returned to the clinical facility for a final gingivitis and plaque examination.
      RESULTS: All 46 subjects complied with the protocol and completed the 4-week
      clinical study. The results of the study indicated that the new manual toothbrush
      was significantly effective in reducing gingivitis and removing plaque after 4
      weeks of use. Specifically, the results indicated a 17-39% reduction in gingival
      sites. In addition, the results indicated plaque removal of up to 96.5% in some
      parts of the mouth.

PMID- 15575438
TI  - A novel method for the evaluation of powered toothbrush oscillation
      characteristics.
AB  - PURPOSE: To assess the vibration characteristics of oscillating objects with the
      scanning laser vibrometer (SLV). A laser is scanned over the surface of a
      vibrating target and the reflected, Doppler frequency shifted beam is used to
      determine the displacement amplitude and frequency of the vibration. This
      communication reports on a preliminary investigation to assess unloaded powered
      toothbrush oscillations, using Scanning Laser Vibrometry. METHODS: Four powered
      toothbrushes were selected for this study including the Sonicare, Philips/Jordan
      Sensiflex HX2520, Braun 3D and Braun D8. Each toothbrush was clamped in position
      and 10 area scans of their heads were taken from the side orientation to
      determine the displacement amplitude and frequency of oscillation. RESULTS: The
      fundamental frequency of oscillation of each brush was determined: Sonicare:
      262.5Hz; Philips: 62.5Hz; 3D: 75Hz and D8: 62.5Hz. The maximum displacement
      amplitude (half the peak-to-peak excursion) for each brush (at the tips of the
      longest bristles) was Sonicare; 2.51 +/- 0.32mm, Philips; 2.60 +/- 0.15mm, Braun
      3D; 2.14 +/- 0.18mm and Braun D8; 2.14 +/- 0.21.

PMID- 15575439
TI  - Effect of the hydration status of the smear layer on the wettability and bond
      strength of a self-etching primer to dentin.
AB  - PURPOSE: To evaluate the microtensile bond strength (MTBS) of a resin-based
      composite to smear layer-covered dentin using a self-etching primer, Clearfil SE
      Bond (CSEB), under two different hydration states. Surface roughness and
      wettability (contact angle measurements) of water and the CSEB primer were also
      evaluated on this substrate. METHODS: Contact angle (CA) measurements were
      performed on four caries-free extracted human third molars. The specimens were
      sectioned parallel to the occlusal surface to expose the moderately deep dentin
      and ground flat (180-grit SiC) under water to provide uniform flat surfaces. In
      two samples, the smear layer was completely air-dried; in the other two
      specimens, the smear layer was briefly air-dried. Contact angle measurements were
      performed to assess wettability of water and CSEB primer using the Axisymmetric
      Drop Shape Analysis technique. Surface roughness (SR) was determined with a
      contact profilometer. In another four molars, CSEB was applied to the smear layer
      covered dentin with both hydration states. Resin build-ups were performed
      incrementally with Tetric Ceram. After storage for 24 hours in water at 37
      degrees C, the teeth were sectioned to obtain bonded beams with an average cross
      sectional area of 1.0 mm2. Each beam was tested in tension in an Instron machine
      at 0.5 mm/minute. Kolmogorov-Smirnov and Student t-tests were performed at a 95%
      significance level. RESULTS: Observed water contact angles were lower on the
      hydrated smear layer but no differences were found between contact angles on
      completely and briefly air-dried smear layer when the primer was used for CA
      measurements. SR was similar for both substrates and MTBS was greater when the
      adhesive was applied on the completely air-dried smear layer.

PMID- 15575440
TI  - Single-step, self-etch adhesives behave as permeable membranes after
      polymerization. Part II. Silver tracer penetration evidence.
AB  - PURPOSE: To investigate the existence of potential water-filled channels in resin
      dentin interfaces of some single-step, self-etch adhesives. METHODS: In
      Experiment I, Prompt L-Pop (3M ESPE) or an experimental adhesive RZ II (Sun
      Medical) were bonded to hydrated dentin and then coupled with a light-cured
      composite that was light-activated immediately upon application. In Experiment
      II, RZ II and FuturaBond (Voco) were similarly bonded to hydrated dentin.
      Unfilled resins were coupled in the dark to the bonded dentin using the chemical
      cured mode, or light-cured mode with a 20-minute delay before light-activation.
      Bonded assemblies were challenged with ammoniacal silver nitrate as a tracer and
      examined with transmission electron microscopy. RESULTS: In Experiment I, two
      types of silver patterns were observed within adhesive layers and hybrid layers:
      interconnecting reticular, finger-like and tree-like patterns that were
      collectively named "water trees", and discrete silver grains. In Experiment II,
      apart from the patterns described above, silver-filled water blisters were also
      observed between the adhesive and the unfilled coupling resin in RZ II. They were
      linked to the pre-existing "water trees" in the adhesive layers via multiple,
      short water bridges. In FuturaBond, similar blisters were located between the
      first adhesive layer and the second adhesive layer that was light-activated after
      placement of the coupling resin.

PMID- 15575441
TI  - An accelerated in vitro model for adhesive testing.
AB  - PURPOSE: To develop a pilot in vitro accelerated laboratory testing protocol for
      assessing marginal sealing capability of dental adhesives. METHODS: Occlusal
      cavities were prepared in 20 human molar teeth and restored with Spectrum TPH
      resin composite. Prime & Bond NT and Prompt L-Pop served as the adhesive for
      eight teeth each. An experimental self-etching adhesive system was used on the
      remaining four teeth. Each specimen was subjected in sequential fashion to the
      following challenges: 400,000 wear cycles in a Leinfelder simulator; 5000
      thermocycles between water baths maintained at 5 degrees C and 55 degrees C with
      a dwell time of 40 seconds in each; and a repetition of the 400,000 wear cycles.
      Polyvinyl siloxane impressions were made at baseline and after each challenge.
      Microleakage was assessed following silver nitrate staining and marginal
      degradation was evaluated using light microscopy and the stone casts made from
      the impressions taken during the project. RESULTS: Microleakage analysis yielded
      the following median leakage values: Prime & Bond NT - 0; Prompt L-Pop - 1; and
      experimental self-etching adhesive - 3. The Wilcoxon sign rank test demonstrated
      significant differences between all three adhesives (P < or = 0.05). Evaluation
      of the stone casts demonstrated that marginal gaps were more prevalent after the
      second wear challenge.

PMID- 15575442
TI  - The adaptation and cavity sealing ability of compomer restorative materials.
AB  - PURPOSE: To examine the sealing ability of compomers, used in combination with
      dentin bonding agents, compared to other classes of tooth-colored materials.
      METHODS: Thirty wedge-shaped cervical cavities were cut in extracted teeth, with
      the gingival cavosurface margin involving dentin. Five cavities each were
      restored with one of the following: the compomers Dyract AP/Prime & Bond NT,
      F2000 Compomer/Adhesive or Hytac Aplitip/Prompt L-Pop; a conventional glass
      ionomer, Ketac Fil Aplicap; a resin-modified glass-ionomer, Fuji II LC Improved;
      or a resin-based composite, Z100 MP/Scotchbond 1. All teeth were restored, stored
      moist for 24 hours, then varnished (except the restorations) before thermocycling
      in rhodamine B dye solution for 1000 cycles (between baths of 6 degrees C and 60
      degrees C). The teeth were sectioned longitudinally through the restorations
      before examination with a confocal microscope. A scale of 0 to 3 was used to
      score the dye leakage along the enamel margin as well as the gingival margin.
      RESULTS: The results showed that at the enamel margin, all materials gave a
      median score of 0 except Z100 MP (median score 3). Leakage was noted at the
      gingival margin of all materials (median score of 3 except Dyract AP with a
      median score of 2).

PMID- 15575443
TI  - Resin bond strength and micromorphology of human teeth prepared with an
      Erbium:YAG laser.
AB  - PURPOSE: To evaluate the in vitro effect of the Er:YAG laser and high-speed
      rotary instrumentation on the bond strength of resin composite to human enamel
      and dentin, and determine which conditioner, either phosphoric acid or a self
      etching primer, resulted in higher bond strengths with either of the surface
      treatments. METHODS: 48 third molars were used. Dentin and enamel specimens were
      sectioned and polished with 600-grit SiC paper and treated either with carbide
      bur or an Erbium:YAG laser and treated with one of three different conditions,
      acid-etch/bonding agent (Scotchbond Multi-Purpose Plus), no etching and same
      bonding agent, and an experimental self-etching primer (EXL 547). After storage
      for 48 hours at 37 degrees C and 100% humidity, specimens were prepared in an
      hourglass shape for microtensile bond test (ca. 1 mm2) and debonded in tension.
      Areas were measured and bond strengths were calculated for each specimen. Failure
      modes, micromorphology of surface treatments and bonding interfaces of
      representative specimens from acid-etched and self-etched groups were analyzed
      with scanning electron microscopy. Means were compared using three-way analysis
      of variance, and Scheffe post-hoc test (P < 0.05) was used to determine
      differences among surface treatments, tooth substrate and conditioners. RESULTS:
      Dentin prepared with the carbide bur and treated with phosphoric acid followed by
      the application of Scotchbond Multi-Purpose had the highest bond strengths (35.7
      MPa). Enamel and dentin prepared with the Er:YAG laser had the highest bond
      strengths when the surfaces were acid-etched followed by Scotchbond Multi-Purpose
      (25.8-21.1 MPa). Carbide bur exhibited higher bond strengths than laser with the
      use of the experimental self-etching primer but laser showed higher bond
      strengths than the bur with the use of Scotchbond Multi-Purpose and no etching.
      The predominant failure mode of most of the treatment conditions was partially
      adhesive between the bonding resin and enamel or dentin, and partially cohesive
      within the bonding resin. SEM analysis revealed the absence of a smear layer on
      laser-treated teeth when compared to untreated control and bur-cut teeth.

PMID- 15575444
TI  - Long-term bond strength of restorations subjected to thermo-mechanical stresses
      over time.
AB  - PURPOSE: To evaluate the long-term effect of thermal and mechanical cycling on
      dentin bond strength to cervical margins of Class II restorations. METHODS: Sixty
      Class II slot cavities were prepared in bovine incisors. The cavities were
      restored with Single Bond and Z-250 composite according to manufacturer's
      instructions. The teeth were then divided into two groups (n = 30): specimens
      that would receive thermo-mechanical load cycling (2,000 cycles 5-55 degrees
      C/100,000 cycles of 50 N loading) (TM) and the control (C). Fifteen specimens
      from each group were tested at baseline and the remaining 30 specimens were
      stored in distilled and deionized water at 37 degrees C and tested after 1 year.
      For microtensile evaluation, the restorations were sectioned perpendicular to the
      cervical bonded interface into 0.7 +/- 0.2 mm thick slabs. The slabs were further
      trimmed at the interface to 1.4 < or = 0.2 mm with a fine diamond bur to produce
      a cross-sectional surface area of ca. 1 mm2. Specimens were then subjected to
      microtensile bond testing. The bond strength data were analyzed using two-way
      ANOVA and Fisher's PLSD test (P < 0.05). Fracture mode analysis was performed
      using SEM. RESULTS: At baseline, bond strength of the TM group was significantly
      lower when compared to the C group (P = 0.012). However, after 1 year storage, a
      significant decrease in bond strength was observed for the C group compared to
      baseline. No significant differences were noted between the C and TM groups at 1
      year. No interaction was observed between groups (C and TM) and storage time (P =
      0.098). For the fracture mode evaluation, at baseline, mixed failure was
      predominant for the C group, and increased after TM. Decreased mixed failure was
      observed after 1-year storage, with a concomitant increase in interphase failure.

PMID- 15575445
TI  - Monitoring of demineralized dentin microhardness throughout and after bleaching.
AB  - PURPOSE: To evaluate the effect of six bleaching agents: Nite White [NW] 10% and
      22% Excel 2Z (Discus Dental), Rembrandt (REM) 10% and 22% (DenMat), Opalescence
      (OPA) 10% and 20% (Ultradent) and a placebo agent on demineralized dentin
      microhardness at different time intervals. METHODS: 105 human dentin slabs (3 x 3
      mm) were embedded, planed and submitted to cariogenic challenges, composed of de-
      and remineralization cycles. For 42 days, specimens were exposed to bleaching
      agents, consisting of applying them daily for 8 hours, removing and storing the
      specimens in artificial saliva for 16 hours. At the end of the bleaching
      treatment, specimens were kept in artificial saliva for 14 days. Knoop
      Microhardness tests were performed on specimens' surface before (baseline),
      during (8 hours, 7, 14, 21, 28, 35 and 42 days) and after bleaching procedures (7
      and 14 days). RESULTS: The ANOVA for split-plot showed significant effect on the
      interaction between bleaching agent and time (alpha =0.05). Tukey's test revealed
      no significant differences on demineralized dentin microhardness exposed to
      bleaching agents until Day 7. Regression analyses demonstrated that NW 10% and
      22% and OPA 10% and 20% increased dentin microhardness in different magnitudes,
      whereas REM 10% and 22% induced mineral loss during bleaching agent application,
      followed by microhardness recovery in the post-treatment period.

PMID- 15575446
TI  - Factors affecting mercury release from dental amalgam exposed to carbamide
      peroxide bleaching agent.
AB  - PURPOSE: To assess, in vitro, the effects of aging and surface polishing on
      mercury release from dental amalgams exposed to 10% carbamide peroxide at two pH
      levels. METHODS: Samples of fresh and aged amalgam, polished and unpolished, were
      treated with 10% carbamide peroxide at pH 4.5 and at pH 6.5 for periods of 1, 4,
      7, 10 and 13 days. At each time period, mercury concentrations in solution were
      measured using a cold-vapor atomic absorption mercury analyzer system and
      compared to control samples treated with phosphate buffer. RESULTS: Amalgam
      samples exposed to 10% carbamide peroxide released significantly more mercury in
      solution than samples exposed to phosphate buffer controls. Mercury release was
      time-dependent and significantly higher in aged amalgam than in fresh amalgam (P
      < 0.001). Mercury release was also pH-dependent and higher in unpolished amalgam.

PMID- 15575447
TI  - In vivo enamel fluoride uptake after use of fluoride products.
AB  - PURPOSE: To evaluate fluoride uptake in enamel after use of products containing
      different fluoride components of distinct oral hygiene regimen in vivo. METHODS:
      84 healthy subjects (24 females and 60 males aged 19-26 years, mean 22.2)
      recruited from the students attending the courses of the Medical Faculty of the
      University of Sassari, Italy, were randomly assigned to one of four treatments
      groups: A: treated with a dentifrice containing sodium monofluorophosphate (1250
      ppm F-); B: treated with dentifrice with 1250 ppm F- from AmF; C: treated with an
      AmF toothpaste (1250 ppm F-) and a mouth rinse with 250 ppm F- from AmF; or D:
      treated with a NaMFP toothpaste (1250 ppm F-) plus 1250 ppm NaMFP varnish. Acid
      etched enamel microbiopsies on the vestibular surface of the first maxillary
      premolar were collected at baseline (to), after 20 days of test product use (t1)
      and after 24 hours without treatment (t2). Fluoride concentration was measured
      using an ion-specific electrode. All measurements were made in triplicate and
      analyzed statistically using two-way factorial ANOVA for independent samples
      standard weighted-means analysis. RESULTS: The fluoride uptake in the enamel
      shows a considerable variation between the groups. Significant differences were
      found both within all products in terms of fluoride concentration in enamel for
      (P < 0.0001 for two-way ANOVA, and later Tukey HSD test). After 20 days of
      treatment, the group using AmF toothpaste plus AmF mouthrinse had a higher
      fluoride uptake than the groups using either of the other products (P < 0.05). In
      conclusion, all products lead to an appreciable amount of fluoride uptake in
      enamel; AmF products led to higher concentrations. The concentration of fluoride
      accumulated during treatment phase remained high after 24 hours following the
      cessation of use.

PMID- 15575448
TI  - Color stability of resin cements after accelerated aging.
AB  - PURPOSE: To study the color stability of different resin cements after
      accelerated aging. METHODS: The color stability of a self-adhesive resin cement
      (Unicem), one resin-based composite cement (Variolink II), one compomer cement
      (Principle) and one hybrid ionomer cement (FujiCEM) was studied. Two curing modes
      of Unicem (self-cured and dual-cured) and Variolink II (light-cured and dual
      cured) were also tested. Specimen disks (n = 5) were prepared with a
      polytetrafluoroethylene split mold and subjected to accelerated aging for 150,
      300 and 450 kJ/m2. Color (CIELAB system) was measured before and after each of
      the three aging cycles on a reflection spectrophotometer. deltaE*, deltaL*,
      deltaC* and deltaH* were calculated and analyzed by ANOVA. RESULTS: The largest
      color change occurred during the first 150 kJ/m2 aging cycle, where deltaE*
      values ranged from 5.6 to 20.5 with Principle showing the least color change and
      FujiCEM the most. The color changes of all the tested materials were perceptible.
      The greatest changes were recorded for deltaL* and/or deltaC*. All specimens
      became significantly rougher and showed evidence of cracking and degradation
      after aging except Variolink II.

PMID- 15575449
TI  - Influence of salivary contamination on marginal microleakage of pit and fissure
      sealants.
AB  - PURPOSE: To assess quantitatively the influence of salivary contamination in
      vitro on marginal microleakage of pit and fissure sealants. METHODS: Forty-eight
      sound human third molars were selected and assigned to three groups: 1)
      Fluroshield (F), 2) Single Bond + Fluroshield (SBF) and 3) Ketac-fil (KF). Each
      group was divided into two subgroups: control (C) and with salivary contamination
      (SC). The occlusal surfaces were etched with 40% polyacrylic acid for 10 seconds
      or 37% phosphoric acid for 30 seconds, for either glass-ionomer or resin-based
      sealants, respectively. Specimens were contaminated with 0.25 mL of fresh human
      saliva for 20 seconds and dried afterwards. The sealants were placed and samples
      were thermocycled, immersed in a 0.2% Rhodamine B solution for 24 hours, embedded
      in acrylic resin and serially sectioned. The sections were viewed under an
      optical microscope connected to a computer and a video camera, and the images
      obtained were digitized. The extent of dye penetration along buccal and lingual
      slopes was measured in millimeters, using specific computer software, and
      converted into percentage, according to the fissures extension. RESULTS: The
      microleakage means (%) were: F/C:0 (+/- 0); F/SC: 31.71 (+/- 31.69); SBF/C: 0 (+/
      0); SBF/SC: 0 (+/- 0); KF/C: 0.98 (+/- 2.79) and KF/SC: 11.82 (+/- 15.45). ANOVA
      and Tukey test showed that salivary contamination provided significant increase
      in microleakage. Under salivary contamination, only SBF provided complete
      marginal sealing. When F and KF were compared, the glass-ionomer cement yielded
      the best sealing.

PMID- 15575450
TI  - Occlusion of dentin tubules by desensitizing agents.
AB  - PURPOSE: To evaluate the occluding effect of five desensitizing agents on human
      dentin tubules. METHODS: 30 buccal and lingual surfaces were prepared from 15
      extracted intact third molars. Each surface was polished with aluminum oxide
      abrasive papers to remove enamel and to expose the underlying dentin in cervical
      area. The flat dentin surfaces were treated with 0.5 M EDTA for 2 minutes to
      expose dentin tubule orifices. The samples were randomly divided into six groups:
      AS - immersed in artificial saliva at 37 degrees C for 2 weeks (control); OX -
      Oxagel (monopotassium oxalate), DU - Duraphat (sodium fluoride), DE -
      Desensibilize (strontium chloride), OD - Odahcam (acidulated phosphate fluoride)
      and SE - Sensodyne (strontium chloride + calcium carbonate abrasive). Dentin
      desensitizers were applied during 2 weeks and after each application the samples
      were kept in artificial saliva at 37 degrees C. The samples were prepared
      according to the scanning electron microscope procedures and were examined at
      x2000 magnification. RESULTS: The results were expressed in percent (%) of tubule
      occlusion and analyzed by ANOVA and Duncan's multiple range test (P < 0.05): AS-
      45.41 +/- 11.65a; OX- 42.65 +/- 11.79a; DU- 47.25 +/- 8.59ab; DE- 49.36 +/-
      18.27ab; OD- 64.43 +/- 15.55b and SE- 65.44 +/- 10.93b. Results suggest that the
      dentin surfaces treated with OD and SE showed higher tubule occlusion when
      compared to AS and OX, but were not different compared to DU and DE treatments.

PMID- 15575451
TI  - Simulated enamel wear during occlusal contact.
AB  - PURPOSE: To investigate in vitro rates of wear for human enamel that opposes
      human enamel by means of two-body and three-body wear tests. METHODS: Flattened
      surfaces (1000-grit) of molars and hemi-spherically prepared enamel cusps were
      perpendicularly opposed and loaded (75.6 N, 1.2 Hz) cyclically 100,000 times in
      both two- and three-body wear test conditions. Wear depths of flat enamel
      specimens were measured with a profilometer, and those of stylus enamel specimens
      were determined by a computer digitizing system at 5, 10, 25, 50, and 100
      thousand cycles. Data were statistically analyzed by three-way ANOVA (P < 0.05),
      and differences between two-body and three-body wear data on flat and stylus
      enamel specimens were determined by Bonferroni-Dunn test. RESULTS: The amount of
      wear after 100,000 cycles in the two-body wear test was 175.6 +/- 144.6 microm
      for flat enamel specimens and 199.3 +/- 72.7 microm for stylus samples. Flat
      enamel, three-body specimens wore 4.9 +/- 1.4 microm and the stylus samples wore
      4.3 +/- 1.0 microm. The data for both flat and stylus enamel specimens subjected
      to the two-body test were significantly greater than those of the three-body wear
      test (P < 0.001).

PMID- 15575452
TI  - Micro-cracking of tooth structure.
AB  - PURPOSE: To determine if the cutting procedure utilized in producing a cavity
      preparation, i.e., a high speed dental handpiece or an Er:YAG laser may be a
      factor in initiating the formation of micro-cracks during or after preparation of
      the cavity and before and after placing and curing the dental composite. METHODS:
      Class I occlusal and Class II MOD preparations were prepared in extracted third
      molars using a high speed dental handpiece equipped with a coarse diamond bur or
      with an Er:YAG laser at 260mJ and 25Hz. Composite was placed into the cavity
      level with the occlusal surface and bulk cured. The extreme factors of a coarse
      diamond bur and bulk curing of the composite were utilized to maximize the
      stresses at the tooth-composite interface. The teeth were vertically sectioned,
      facio-lingually, and examined, along with resin replicas, under a scanning
      electron microscope (SEM) to look for the presence of microcracks at the
      composite/enamel interface and composite/dentin interface. RESULTS: SEM
      examination indicated that micro-cracking of the tooth structure was not
      significant or consistent in any of the specimens examined. This study was unable
      to confirm that micro-cracks form at the composite/tooth interface.

PMID- 15575453
TI  - Evidence-based practices in health care: social work possibilities.

PMID- 15575454
TI  - Effects of social work intervention on nonemergent pediatric emergency department
      utilization.
AB  - The purpose of this study was to determine whether social work intervention would
      reduce nonemergent visits to the emergency department and increase scheduled
      pediatric visits. A high-risk repeater group of 104 pediatric patients with three
      or more emergency department visits was randomly selected to receive social work
      intervention. Control and intervention groups were compared for inappropriate
      emergency department utilization and scheduled primary care visits. Pre- and
      postintervention emergency department visits were significantly reduced in the
      intervention group compared with the group that received no intervention and with
      prior utilization. Scheduled visits declined in the control group but increased
      by 26 percent in the intervention group.

PMID- 15575455
TI  - Post-acute home care and hospital readmission of elderly patients with congestive
      heart failure.
AB  - After inpatient hospitalization, many elderly patients with congestive heart
      failure (CHF) are discharged home and receive post-acute home care from informal
      (family) caregivers and formal service providers. Hospital readmission rates are
      high among elderly patients with CHF, and it is thought that use of informal and
      formal services may reduce hospital readmission during the post-acute period.
      Using proportional Cox regression analysis, the authors examined the independent
      and joint effects of post-acute informal and formal services on hospital
      readmission. No evidence of service impact was found. Rather, hospital
      readmission was associated with a longer length of CHF history and noncompliance
      with medication regimes. Research, policy, and practice implications are
      discussed.

PMID- 15575456
TI  - Job satisfaction of home health social workers in the environment of cost
      containment.
AB  - This national survey examined the job satisfaction of 228 home health social
      workers in the restrictive reimbursement environment of the Medicare interim
      payment system. Administrators' helpfulness in resolving ethical conflicts
      between patient access to services and agency financial priorities contributed
      significantly to greater satisfaction in regression analysis. Supervisors'
      helpfulness in resolving the conflict moderated the difficulty of resolving the
      conflict. The frequency with which workers believed they had to compromise
      professional ethics contributed significantly to less satisfaction. Implications
      for practitioners, supervisors, administrators, and educators are discussed.

PMID- 15575457
TI  - Practice with people with severe mental illness: rewards, challenges, burdens.
AB  - The authors surveyed a random sample of 1,200 NASW members in post-master's
      practice in mental health to identify their attitudes toward practice with people
      with severe mental illness. Contrary to the literature that claims social workers
      have abandoned vulnerable populations or have negative attitudes toward this
      population, the authors found that the majority practice with this clientele and
      find their practice rewarding. Most of the respondents' frustration and obstacles
      in practice were related to systemic problems, not client-related problems.
      Respondents' recommendations for education of future practitioners are presented.

PMID- 15575458
TI  - Perceptions of domestic violence: a dialogue with African American women.
AB  - Although empirical research has accumulated over the past 20 years regarding
      African Americans and domestic violence, many questions remain about African
      American perceptions of domestic violence. This article explores African American
      women's perceptions about domestic violence through three focus groups held at a
      New York social services agency. The findings point to the need to better
      understand diverse perceptions of domestic violence, to find culturally competent
      methods of addressing the inaccessibility of domestic violence services, to
      increase culturally appropriate public education, and to conduct more research on
      the connection between domestic violence and child welfare in communities of
      color.

PMID- 15575459
TI  - Maternal custody status and living arrangements of children of women with severe
      mental illness.
AB  - The authors report results of a pilot study on the custody status of 20 women
      with severe mental illnesses who were parents of a total of 76 children. The
      mothers had some of their children living with them and others dispersed among
      kinship and nonkinship arrangements. Qualitative findings illustrate how
      bewildered these women were about the status of children placed outside the home
      and their ability to obtain custody or maintain contact with their children. The
      authors suggest that social workers working with women with severe mental illness
      inquire about and "map" the whereabouts of women's children, help mothers mediate
      legal and social services delivery systems, and help mothers exercise their
      rights when there is risk of termination of parental rights.

PMID- 15575460
TI  - A multiple-family group intervention for homeless families: the weekend retreat.

PMID- 15575461
TI  - Psychosocial needs of women with breast cancer: how can social workers make a
      difference?

PMID- 15575462
TI  - The promise of public housing as a community-based model of health care.

PMID- 15575463
TI  - Will the United States ever have universal health care?

PMID- 15575464
TI  - Flu vaccine shortage creates ethical issues, safety challenges.
AB  - Decisions may have to be made as to whether staff or patients get priority.
      Centers for Disease Control and Prevention guidelines help ease choices when it
      comes to inoculating workers. Quality professionals should be aware of the legal
      implications of their decisions.

PMID- 15575465
TI  - Longitudinal records enable instant QI changes.
AB  - The system will save the hospital an estimated $10 million per year. Computerized
      physician order entry is integrated with other electronic records at the
      facility. A done-deal attitude by leadership gets staff on board in 18 months.

PMID- 15575466
TI  - Survey a launching pad for wide-ranging improvement.
AB  - Frontline employees were solicited for recommendations for improvement
      opportunities. Several teams were formed, with coaches and team leaders receiving
      training before starting projects. Project outlines and successes are shared
      through a database on the hospital intranet.

PMID- 15575467
TI  - Strong collaboration sets QI program apart.
AB  - Quality initiatives are not viewed in silos, but in a global, hospitalwide
      framework. All new physicians must learn the computer system--and treat nurses
      with respect. Facility participates in as many state, regional, and national
      benchmark projects as possible.

PMID- 15575468
TI  - ED crisis presents a new set of quality challenges.
AB  - Emergency department (ED) coverage crisis may affect not only specialist care but
      basic emergency services. Finances and lifestyle issues keep many specialists
      from covering the ED. Fee-for-service programs and stipends for physicians can
      provide a coverage incentive.

PMID- 15575469
TI  - [Misdiagnosis and mistreatment of pulmonary cancer].

PMID- 15575470
TI  - [The role of psychiatry in medicine].

PMID- 15575471
TI  - [Effects of prognostic parameters and radiotherapy on survival of patients with
      pulmonary cancer].
AB  - AIM: To analyze factors influencing expected survival of pulmonary cancer (PC)
      patients given radiotherapy, i.e. age of the patient, stage of the disease, size
      of the tumor, involvement of the lymph nodes, a total focal dose, space
      distribution of the dose. MATERIAL AND METHODS: Among PC patients 87% were males
      and 73.9% were 60 years of age and older. Local PC (stage IIIa and IIIb) was
      diagnosed in 65.2%. Non-small-cell PC was in 83.8%. Effects of radiotherapy on
      the survival was analysed in 115 patients. Total focal doses made up 30 Gy (3.0
      Gy/10 fractions) to 70 Gy (2.0 Gy/35 fractions). RESULTS: Longer survival was
      achieved after irradiation with greater dose and modern three-dimentional
      planning of conformic radiotherapy. A significant prolongation of the survival
      was seen in raising the total focal dose to 50 Gy. There is a correlation between
      the dose and conformity of the dose distribution. During the study 58.2% patients
      died. CONCLUSION: Assessment of the survival of PC patients given radiotherapy
      has shown that negative prognostic factors are the following: PC stage IIIA, IIIB
      and IV, extensive local spread of the tumor, large primary tumor, involvement of
      the lymph nodes.

PMID- 15575472
TI  - [Use of interleukine-2 in a patient with renal cancer and paraneoplastic
      vasculitis].

PMID- 15575473
TI  - [Present-day antidepressants: new perspectives in general clinical practice (a
      review)].

PMID- 15575474
TI  - [Pirasidol treatment of depression in elderly patients with somatic diseases].
AB  - AIM: To study efficacy and tolerance of pirasidol in elderly patients with
      somatic diseases and depression. MATERIAL AND METHODS: The study was made in 30
      patients over 55 years of age with a mild or moderate depressive episode. The
      efficacy of a 6 week treatment with pirasidol was assessed by somatic
      examination, Hamilton depressive scale (17 points), General Clinical Impression
      Scale, 5-score subjective state scale. RESULTS: Pirasidol treatment led to a 36%
      decrease in intake of drugs. The patients took much lower doses of non-narcotic
      analgetics, nitroglycerine, tranquilizers, enzymatic medicines. The highest
      efficacy was seen in patients with exacerbation of somatic diseases which reduced
      faster in addition of pirasidol to somatotropic therapy. Pirasidol is well
      tolerated, no interaction with other drugs was found. CONCLUSION: The
      antidepressant pirasidol showed efficacy against depression in elderly patients
      with somatic pathology. It can be recommended as a drug of choice for treatment
      of depression in elderly patients with somatic diseases.

PMID- 15575475
TI  - [Algorithm of life quality evaluation for patients with psychosomatic diseases].
AB  - AIM: To elaborate the algorithm for evaluation of quality of life (QL) in
      patients with psychosomatic diseases. MATERIAL AND METHODS: AMPI, Spilberger
      Khanin anxiety test, the procedures 'general state, activity, mood" and
      "personality differential". RESULTS: The algorithm of QL evaluation comprises a
      questionnaire consisting of 48 questions divided into 3 blocks. Quality of the
      somatic state was assessed by restrictions in exercise, self-care, everyday
      activity. A psychological component of QL was determined by the presence of
      depression, anxiety, emotional effects on everyday and professional activity; the
      social component--by relations in office, family, medical personal. The procedure
      was standardized, so QL should be considered as high at 97-144 points, good 87
      96, satisfactory 44-86, unsatisfactory results were at 26-43 points, poor--at 0
      25 points. CONCLUSION: The proposed technique of QL of psychosomatic patients
      proved its validity and reliability. Therefore, it can be recommended for design
      of psychosocial and medical rehabilitative measures as well as for assessment of
      efficacy of these measures.

PMID- 15575476
TI  - [Vertigo in neurological and therapeutic practice (lecture)].

PMID- 15575477
TI  - [Diagnosis and treatment of hypothyroidism: current principles ( a review)].

PMID- 15575478
TI  - [Metabolic syndrome of insulin resistance: basic conception and consequences ( a
      review)].

PMID- 15575479
TI  - [Physiological role and significance of magnesium in therapy (a review)].

PMID- 15575480
TI  - [Pathogenesis and diagnosis of chronic venous insufficiency. Update (lecture)].

PMID- 15575481
TI  - [Current trends in therapy of chronic venous insufficiency (lecture)].

PMID- 15575482
TI  - [Use of alpha-adrenoblockers in therapy of benign prostatic hyperplasia in
      patients with arterial hypertension].
AB  - AIM: To compare efficacy and tolerance of tonocardin (doxazosin) and omnik
      (tamsulosin) in the treatment of benign prostatic hyperplasia (BPH) in
      hypertensive patients. MATERIAL AND METHODS: Group 1 patients (n = 115, age 44-81
      years) with BPH and mild or moderate arterial hypertension (AH) treated with one
      antihypertensive drug (ACE inhibitor--48, calcium antagonist--26, beta-blocker-
      22, diuretic--19) were given tonocardin in a single daily dose from 1 to 4 mg for
      12 weeks. Group 2 patients (n = 30, age 67-81 years) with BPH and severe AH
      treated with two antihypertensive drugs and more were given omnik in a single
      daily dose 0.4 mg for 12 weeks. RESULTS: In group 1, tonocardin treatment
      resulted in lowering of a total symptoms score by IPSS scale from 17.5 +/- 3.6 to
      14.7 +/- 1.3 points, of quality of life from 4.3 +/- 0.7 to 3.9 +/- 0.3, in a
      rise of maximal velocity of urine flow (Qmax) from 7.8 +/- 1.2 to 9.4 +/- 0.6
      ml/s; residual urine (R) reduced from 112.4 +/- 8.6 to 64.5 +/- 10.2 ml).
      Systolic arterial pressure went down from 150.5 +/- 13 to 139.8 +/- 13.3 mm Hg,
      diastolic pressure fell from 86.9 +/- 6.1 to 80.8 +/- 7.1 mm Hg. In group 2,
      omnik resulted in IPSS scale points lowering from 17.7 +/- 3.5 to 15 +/- 1.1, QOL
      from 4.5 +/- 0.2 to 3.8 +/- 0.2, Qmax from 7.4 +/- 1.1 to 9.2 +/- 0.5 ml/s, R
      from 107.5 +/- 12.7 to 63.4 +/- 9.7 ml. Arterial pressure did not change much.
      CONCLUSION: Tonocardin and omnik are effective and safe not only in the treatment
      of BPH but also of BPH combination with AH.

PMID- 15575483
TI  - [Erectile dysfunction in patients with ischemic heart disease (review )].

PMID- 15575484
TI  - [Basic therapy of rheumatoid arthritis with leflunomide (review)].

PMID- 15575485
TI  - [ACE inhibitors in the treatment of ischemic heart disease and prevention of its
      complications (review)].

PMID- 15575486
TI  - [Periportal cardiomyopathy (a case report)].

PMID- 15575487
TI  - [Significance of antibacterial therapy of Chlamydophila pneumoniae infection in
      patients with bronchial asthma].
AB  - AIM: To study effects of eradication of Chlamydophila pneumoniae CP) infection in
      bronchial asthma (BA) on BA course and changes in quality of life (QOL) in BA
      patients. MATERIAL AND METHODS: 194 BA patients in clinical remission
      participated in the trial. Microbiological diagnosis of asymptomatic CP infection
      was made serologically (ELISA, indirect enzyme immunoassay) using polymerase
      chain reaction. Clinical and biochemical tests, assessment of pulmonary
      ventilation function, QOL by AQLQ during 6-week antimicrobial therapy were made
      in 56 patients. RESULTS: Patients with stable BA had high frequency of
      serological signs of clinically asymptomatic CP infection (52%) deteriorating BA
      symptoms and QOL. Antibacterial therapy of latent CP infection with azitromycin
      significantly improved BA course and QOL of BA patients. CONCLUSION: When
      laboratory tests detect CP infection in patients with long-term course of BA,
      especially in smoking males with moderate and severe BA it is clinically valid to
      prescribe addition of azitromycin to basic antiinflammatory treatment of BA.

PMID- 15575488
TI  - [Knowledge of cardiovascular disease risk factors in open population of Tyumen
      and social gradient].
AB  - AIM: To study knowledge of cardiovascular disease (CVD) risk factors (RF) in open
      population of Tyumen with reference to social gradient. MATERIAL AND METHODS:
      Knowledge of CVD RF was studied in 2248 citizens of Tyumen (men and women, age 25
      64 years) by means of mail questionnaire survey. The knowledge was assessed with
      consideration of education, occupation and marriage status. RESULTS: The
      examinees with primary education and manual labour workers were found to have
      little knowledge of the CVD RF while those with university education, engineers
      and specialists were well informed. Married population, widows and widowers knew
      about CVD RF more than divorced. CONCLUSION: The results of the study can serve a
      basis for a large-scale prophylactic program in open population of Tyumen.

PMID- 15575489
TI  - Plasticity of the hippocampal place cell representation.
AB  - The role of the hippocampus in the representation of 'place' has been attributed
      to the place cells, whose spatially localised firing suggests their participation
      in forming a cognitive map of the environment. That this map is necessary for
      spatial memory formation is indicated by the propensity of almost all
      navigational tasks to be disrupted by hippocampal damage. The hippocampus has
      also long been implicated in the formation of episodic memories, and the
      unusually plastic nature of hippocampal synapses testifies to its probable
      mnemonic role. Arguably, the place cell representation should, if it is to
      support spatial learning, be modifiable according to known principles of synaptic
      reorganization. The present article reviews evidence that the place cell
      representation is indeed plastic, and that its plasticity depends on the same
      neurobiological mechanisms known to underlie experimentally induced synaptic
      plasticity. Inferences are drawn regarding the architecture of the spatial
      representation and the principles by which it is modified. Spatial learning is
      promising to be the first kind of memory which is completely understood at all
      levels, from molecular through circuitry to behaviour and beyond.

PMID- 15575490
TI  - A behavioral assessment of hippocampal function based on a subregional analysis.
AB  - The purpose of this review is to determine whether specific subregions (dentate
      gyrus [DG], CA3, and CA1) of the hippocampus provide unique contributions to
      specific processes associated with intrinsic information processing exemplified
      by novelty detection, encoding, pattern separation, pattern association, pattern
      completion, retrieval, short-term memory and intermediate-term memory. Based on
      anatomical neural network organization, electrophysiology of cellular activity,
      lesions, early gene activation, and computational modeling, it can be shown that
      there exists extensive cooperation among the three subregions of the hippocampus,
      but there also exists reliable specificity of function for each of the subregions
      of the hippocampus. The primary process supported by the DG subregion of the
      hippocampus can be characterized by orthogonalization of sensory inputs to create
      a metric spatial representation. Furthermore the DG participates in conjunction
      with CA3 in supporting spatial pattern separation. The CA3 subregion of the
      hippocampus supports processes associated with spatial pattern association,
      spatial pattern completion, novelty detection, and short-term memory. The CA1
      subregion of the hippocampus supports processes associated with temporal pattern
      association, temporal pattern completion, and intermediate-term memory.
      Furthermore, the CA3 in conjunction with CA1 supports temporal pattern
      separation. All the above-mentioned processes are assumed to reflect intrinsic
      processing of information within the hippocampus. The diversity of functions
      associated with the different subregions of the hippocampus suggests that one
      should not treat the hippocampus as a single entity, but rather that one should
      concentrate on elucidating further the functions of both dorsal and ventral
      subregions of the hippocampus and pathways that directly connect each of the
      subregions as well as their connections with the entorhinal cortex.

PMID- 15575491
TI  - Mouse models of Alzheimer's disease: insight into treatment.
AB  - Mice overexpressing mutant Alzheimer's disease (AD)-related proteins exhibit many
      of the neuropathological and behavioral features of the human disease. Transgenic
      animals have been created that express mutations in the amyloid precursor protein
      (APP), presenilin (PS)1, and PS2, and also animals expressing more than one of
      these mutations. For example, in APP mouse models, there are age-related
      accumulations of amyloid-beta (Abeta)-containing neuritic plaques in the
      hippocampus and cerebral cortex, activation of astrocytes and microglial cells in
      regions containing plaques, and degeneration of cholinergic nerve terminals in
      brain regions that eventually become plaque containing. Missing in the APP and PS
      mouse models are neurofibrillary tangles and robust neuronal loss in cerebral
      cortical and subcortical regions such as the basal forebrain cholinergic and
      locus coeruleus noradrenergic nuclei. Neurofibrillary tangles can be produced in
      mice expressing mutant tau protein, and the tangle formation is further enhanced
      in animals that also express mutant APP. Studies in APP mouse models indicate
      that, like AD, there are abnormalities in adult hippocampal neurogenesis. The
      animal models of AD have been used to develop and test treatments that reduce
      brain levels of the Abeta42 protein, neuritic plaque load and glial activation,
      and some have been found to restore learning and memory function. If such
      treatments can be shown to stop the neurodegenerative process and restore
      hippocampal neurogenesis, damaged brain circuits may be replaceable in patients
      with AD.

PMID- 15575492
TI  - Interactions between cognitive and sensorimotor functions in the motor cortex:
      evidence from the preparatory motor sets anticipating a perturbation.
AB  - The many signs of cognitive processes in the activation pattern of the primary
      motor cortex or in corticospinal (CS) excitability gave rise to the idea that the
      motor cortex is a crucial node in the processing of cognitive information related
      to sensorimotor functions. Moreover, it became clear that the preparatory motor
      sets offer a privileged window to investigate the interaction between cognitive
      and sensorimotor function in the motor cortex. In the present review, we examine
      how the study of the preparatory motor sets anticipating a mechanical movement
      perturbation contributes to enlightening this question. Following the initial
      observation made by Hammond that some components of the stretch reflex can be
      modulated by a prior intention either to resist or to relax in response to a
      subsequent perturbation, first evidence of the phenomenon was obtained in
      behaving monkeys. Moreover, this study related this peripheral fact to the
      observed anticipatory activity of motor cortex neurons after a prior instruction
      telling the animal how to respond to the subsequent perturbation, which triggered
      the instructed movement. Indeed, this anticipatory activity was found to be
      different according to the instruction. In the 1980s, this work inspired a lot of
      studies in human beings that brought support to the idea of a cognitive tuning of
      the long latency stretch response (LLSR). Specifically, the MI component of the
      response was shown to be modulated by a prior intent to resist versus to let go
      when faced with the perturbation. Recently, new approaches have been developed to
      obtain evidence of a cognitive tuning of CS excitability, thanks to transcranial
      magnetic stimulation (TMS). TMS has been used both as a reliable tool for
      quantifying the CS excitability via the motor evoked potentials (MEPs), and to
      centrally perturb the organization of movement. Such central perturbations offer
      the unique opportunity to activate the descending motor tracts while shunting,
      for a short time period, the ascending tracts assisting the movement. Thus, CS
      excitability was measured before the movement was perturbed. These studies
      demonstrated the readiness of the CS tract to be involved in anticipatory
      compensatory responses to central movement perturbations induced by TMS in
      relation to the subject's cognitive attitudes. The question of the cerebral
      regions upstream of the motor cortex that could be responsible for this
      modulation in CS excitability remains largely open.

PMID- 15575493
TI  - [Cardiotoxicity induced by chemotherapy: possibilities of diagnosis].
AB  - The authors give a brief summary about the process and significance of
      cardiotoxicity produced by chemotherapy and irradiation used for malignancy.
      After the introduction, those invasive and noninvasive processes are put into
      focus and explained in detail, which are applied in the research of the effects
      of cardiotoxic chemotherapy. The clinical importance of this research is the life
      prolongation effect of the treatment, which allows the late-appearing toxic
      cardiomyopathy, resulting in congestive heart failure and increasing mortality.
      Summarizing the last decade's progress in research, it is evident that even in
      the planning of chemotherapy, the cardiovascular risks have to be taken into
      account, because they can greatly influence the cardiac side effect of the
      treatment.

PMID- 15575494
TI  - [Clinical and pharmacological aspects of rifaximin, local antibiotic therapy in
      intestinal disorders].
AB  - The authors report pharmacokinetics and indications of rifaximin and the results
      of clinical studies. Rifaximin has a large antibacterial spectrum with a good
      therapeutic effect on both gram positive and gram negative aerob and anaerob
      bacteria. Practically there is no absorption (< 1%) following oral administration
      with a high concentration in gastrointestinal mucosa (8000 microg/g). No increase
      in absorption can be detected in intestinal damage caused by inflammatory bowel
      disease. The remarkable safety profile of rifaximin is due to its negligible
      quality of absorption. According to the clinical studies rifaximin could be an
      adequate therapeutic approach in all gastrointestinal diseases and interventions
      when antibacterial therapy is needed.

PMID- 15575495
TI  - [Single cell DNA analysis: possibilities, methods, implications in relation to
      stem cell therapy].
AB  - In the analysis of circulating tumor cells or in the preimplantation genetic
      diagnosis it is frequently necessary to examine one single cell. Some methods are
      appropriate to isolate single cells: Laser Assisted Microdissection, magnetic
      cell separation or FACS. The use of the whole genome amplification methods are
      needful, because the amount of the DNA extracted from the isolated cells is very
      low and inappropriate for additional examinations. With different molecular
      biological methods (e.g. sequencing, chip-technology) it is possible to determine
      genetic alterations in the analysed cells, and to return the modified cells with
      in vitro gene technological methods (viral vectors, non viral methods). Our aim
      is to summarize the methods and the possible technical problems developing during
      the process of the single cell molecular biological analysis.

PMID- 15575496
TI  - [The role of clinical audit in the quality improvement of health care].
AB  - The aim of clinical audit is continuous improvement of the quality of care
      through systematic and critical review of current practice against explicit
      criteria and the implementation of change if necessary. The audit is a regular
      multidisciplinary activity by which all participants of care including doctors,
      nurses and other health professionals carry out a systematic review of their own
      practice. Data collected during the process of audit should be handled with care,
      and individual data concerning care-givers, patients or health professionals must
      be treated confidentially. Clinical audit needs realistic timeframe and necessary
      resources as well as tolerant culture of learning organisations. Furthermore the
      success of clinical audit depends on the commitment and support of the management
      of the organisations. Clinical audit could relatively easily be embodied into the
      current practice of peer-review processes and other quality improvement
      initiatives in Hungary. Widespread and systemic application of clinical audit may
      improve the quality of patient care and maintain the trust of the population.
      However, clinical audit should be effective and cost-effective. The recently
      published methodological guideline by the Ministry intends to promote good
      practice in clinical audit.

PMID- 15575497
TI  - [The good and the bad. The abuse of mass-media. Tasks in child care].
AB  - People would like to spend their increasing spare-time with entertainment and,
      therefore, the use of media has been growing. This has both advantages and
      disadvantages (physical and mental disturbances in their growing). Pediatricians
      need to know this problems and to recognize it in time to avert.

PMID- 15575498
TI  - [Human microsatellites: mutation and evolution].
AB  - Microsatellites (MSs) are short tandem DNA repeats with the repetitive motif of
      two to six nucleotides, forming tracts up to hundreds of nucleotides long.
      Notwithstanding the active use of MSs in genetic studies of various biological
      problems, the reasons for their wide occurrence in the genome, their possible
      functions, and mutational behavior are still unclear. The mutation rate in MS
      repeats is on average several orders of magnitude higher than in the remaining
      DNA, which allows for direct estimation of evolutionary transformation rate in
      nucleotide sequences of the genome. Mutation process in MSs is species-specific;
      furthermore, within a species it differs among loci with different repeat size,
      among alleles of one locus, and among individuals of different sex and age. Most
      MS mutations are caused by DNA slippage during replication but the probability of
      this event depends on the locus. In this review, a number of models of MS
      evolution are discussed, which account for the relationship between mutation rate
      and allele size, different mutation direction in alleles of different size, and
      the appearance of point mutations within repeat tracts restricting allele size.
      The MS evolution is considered mainly in the context of selective neutrality,
      although there is evidence showing functional significance of some variants of
      tandem repeats and thus their possible selective value.

PMID- 15575499
TI  - [The use of c-mos nuclear gene as a phylogenetic marker in tetraonidae birds].
AB  - A 480-bp fragment of nuclear c-mos gene was sequenced in nine bird species
      representing four genera of the family Tetraonidae. It was demonstrated that
      nuclear genome region examined was highly conservative. The data were used to
      construct phylogenetic relationships among the c-mos gene sequences in
      Tetraonidae. The data obtained point to a paraphyletic origin of hazel grouse
      (Bonasa bonasia) and ruffed grouse (Bonasa umbellus).

PMID- 15575500
TI  - [Characterization and comparative analysis of DNA from the pericentric
      heterochromatin of chromosome 2 of Anopheles atroparvus V. Tiel (Culicidae,
      Diptera)].
AB  - The minilibrary containing DNA sequences from the diffuse pericentric
      heterochromatin from the right arm of Anopheles atroparvus V. Tiel (Culicidae,
      Diptera) chromosome 2 (2R) was generated by use of chromosome microdissection
      technique. Southern-blot hybridization of the minilibrary fragments with the
      labeled genomic DNA of A. atroparvus and analysis of their primary structure
      showed that this heterochromatin region contained repeated DNA sequences differed
      by their primary structure and the number of copies. These were mostly AT-rich
      sequences harboring the features characteristic of the S/MAR regions. Based on
      the clones homology to the sequences from the An. gambiae and Drosophila
      melanogaster genomes, it was demonstrated that the pericentric heterochromatin
      from the right arm of An. atroparvus chromosome 2 contained gypsy-like
      transposable elements, as well as the sequences homologous to the structural
      genes. In situ hybridization with the chromosomes of A. atroparvus and of the two
      representatives of the Anopheles maculipennis species complex, A. messeae and A.
      beklemishevi, showed that pericentric regions of all these chromosomes contained
      DNA sequences homologous to the sequences from the region-specific minilibrary.
      Cloned fragments of conserved repetitive DNA revealed upon interspecific Southern
      blot hybridization of the clones with the labeled genomic DNA of A. messeae can
      be utilized in further investigations of evolutionary rearrangements of the
      pericentric heterochromatin within the Anopheles maculipennis species complex.

PMID- 15575501
TI  - [Study of allelic polymorphism of (GATA)n-containing loci in parthenogenetic
      lizards Darevskia unisexualis (Lacertidae)].
AB  - The genesis of mini- and microsatellite loci, which is under extensive study in
      humans and some other bisexual species, have been virtually overlooked in species
      with clonal mode of reproduction. Earlier, using multilocus DNA fingerprinting,
      we have examined variability of some mini- and microsatellite DNA markers in
      parthenogenetic lizards from the genus Darevskia. In particular, mutant (GATA)n
      restrictive DNA fragments were found in Darevskia unisexualis. In the present
      study, we examined intraspecific polymorphism of three cloned loci of D.
      unisexualis--Du323, Du215, and Du281--containing (GATA)7GAT(GATA)2, GAT(GATA)9,
      and (GATA)10TA(GATA) microsatellite clusters, respectively. Different levels of
      intrapopulation and interpopulation variability of these loci were found. Locus
      Du281 showed the highest polymorphism--six allelic variants (in the sample of 68
      DNA specimens). Three alleles were found for locus Du215. The Du325 locus was
      electrophoretically invariant. The primers chosen for loci Du323, Du215, and
      Du281 were also used for PCR analysis of homologous loci in two presumptive
      parental bisexual species, D. valentini and D. nairensis. The PCR products of the
      corresponding loci of the parental species had approximately the same size
      (approximately 200 bp) as their counterparts in D. unisexualis, but the
      polymorphism levels of the paternal, maternal, and hybrid species were shown to
      be somewhat different. These data on the structure of the D. unisexualis loci
      provide a possibility to study genetic diversity in the parthenogenetic species
      D. unisexualis and other related unisexual and bisexual species of this genus,
      which can provide new information on the origin of parthenogenetic species and on
      the phylogenetic relationships in the genus Darevskia. These data can also be
      used for resolving problems of marking the lizard genome, which is still poorly
      studied.

PMID- 15575502
TI  - [Evaluation of polymorphism at microsatellite loci of spring durum wheat
      (Triticum durum Desf.) varieties and the use of SSR-based analysis in
      phylogenetic studies].
AB  - Polymorphism at 28 SSR loci was analyzed and described in 45 cultivars of spring
      durum wheat created in the former USSR and Russia during the last 80 years. Each
      cultivar was shown to have a unique allele combination. This allows SSR markers
      to be used to identify durum wheat varieties. Meanwhile, these markers can hardly
      be used to detect phylogenetic relationships among varieties and to specify their
      pedigrees, because genetic distances calculated on the basis of these markers do
      not correlate with the distance calculated by coefficient of parentage.

PMID- 15575503
TI  - [Analysis of intraspecific divergence of hexaploid wheat Triticum spelta L. by
      chromosome C-banding].
AB  - Intraspecific divergence of hexaploid wheat Triticum spelta was studied by
      chromosome C-banding in 41 accessions of different geographic origins. The spelt
      accessions did not differ in karyotype structure or heterochromatin distribution
      from common wheat, but showed greater intraspecific polymorphism for chromosome
      rearrangements (translocations, inversions) and banding patterns. On evidence of
      C-banding patterns, spelt was assumed to occupy an intermediate position between
      tetraploid and hexaploid wheat species. Accessions of the Asian spelt subspecies
      had more diverse banding patterns than European accessions. A relatively high
      frequency of chromosome rearrangements was observed in Iranian accessions. Visual
      analysis revealed high uniformity of chromosome banding patterns in T. spelta
      populations of Afghanistan, Spain, and Germany (Bavarian group), suggesting a
      significant role of the founder effect in their evolution.

PMID- 15575504
TI  - [Genetic diversity and differentiation of Gmelin larch Larix gmelinii populations
      from Evenkia (Central Siberia)].
AB  - Within- and among-population diversity of Gmelin larch Larix gmelinii (Rupr.)
      Rupr. from Evenkia was inferred from data on 17 genes determining allozyme
      diversity of ten enzymes. More than 50% of the genes proved to be polymorphic. On
      average, each tree was heterozygous at 9.2% genes. Heterozygosity expected from
      the Hardy-Weinberg proportions was higher, 12.5%. A deficit of heterozygous
      genotypes was observed in all populations under study and attributed to
      inbreeding. With Wright's F statistics, average individual inbreeding was
      estimated at 26.6% relative to the population (F(IS)) and at 27.8% relative to
      the species (F(IT)). The greatest deficit of heterozygosity was observed for the
      youngest population. Within-population variation accounted for more than 98% of
      the total variation, while the contribution of among-population variation was
      1.66%. Genetic distance between populations varied from 0.0025 to 0.0042,
      averaging 0.0035.

PMID- 15575505
TI  - [Genetic and taxonomic diversity of the house mouse Mus musculus from the asian
      part of the former Soviet Union].
AB  - Genetic diversity of the house mouse Mus musculus from 12 local populations (n =
      65) of the central and eastern parts of the former Soviet Union was examined
      using RAPD-PCR. About 400 loci were identified, encompassing approximately 500 kb
      of the mouse genome. Genetic diversity was assessed using NTSYS, POPGENE, TFPGA,
      and TREECON software programs. In general, the house mouse sample from the
      regions examined was characterized by moderate genetic variation: polymorphism P
      = 95.6%, P99 = 60.7%, P95 = 24.2%; heterozygosity H = 0.089; the mean observed
      number of alleles n(a) = 1.97; effective number of alleles n = 1.13;
      intrapopulation differentiation deltaS = 0.387; gene diversity h = 0.09.
      Individual local populations displayed different levels of genetic isolation: the
      genetic subdivision index G(st) varied from 0.086 to 0.324 at gene flow Nm
      varying from 5.3 to 1.05, while the interpopulation genetic distance D(N) ranged
      from 0.059 to 0.186. Most of the genetic diversity of the total sample resided
      within the local populations: H(S) = 0.6, total gene diversity H(T) = 0.09. The
      exact test for differentiation, however, did not confirm the affiliation of all
      the mice examined to one population: chi2 = 1446, d.f. = 724, P = 0.000.
      Molecular markers specific to four subspecies (musculus, castaneus, gansuensis,
      and wagneri) were identified. Moreover, in some cases the populations and
      individual animals exhibited traits of different subspecies, suggesting their
      introgressive hybridization. It was demonstrated that the house mouse fauna on
      the territories investigated was characterized by the prevalence of musculus
      specific markers, while gansuensis-specific markers ranked second. The castaneus
      specific markers were highly frequent in the Far East, but almost absent in
      Central Asia, where wagneri-specific markers were detected. It was suggested that
      house mice from Turkmenistan could belong to one of the southern subspecies,
      which had not deeply penetrated into the Asian fauna of the former Soviet Union.
      In phenogenetic (UPGMA) and phylogenetic (NJ) reconstructions this form with the
      high bootstrap support was placed at the tree base, while the isolation of other
      clusters was not statistically significant. It is thus likely that the house mice
      from Turkmenistan are closest to the ancestral form of the genus Mus on the
      territory of the former Soviet Union.

PMID- 15575506
TI  - Genetic variation analysis within and among six varieties of common carp
      (Cyprinus carpio L.) in China using microsatellite markers.
AB  - Five microsatellites were used to study the genetic diversity and genetic
      structure of one wild and five domestic varieties of common carp in China (the
      Yangtze River wild common carp, Xingguo red carp, purse red carp, Qingtian carp,
      Russian scattered scaled mirror carp and Japanese decorative carp). All loci in
      this study showed marked polymorphism with the number of alleles from 4 to 13.
      Domestic varieties (except Xingguo red carp) showed less genetic diversity than
      the Yangtze River wild common carp in terms of allelic diversity. Population
      differentiation was assessed and each combination of populations displayed
      significant differentiation (p < 0.05) with the exception of that between the
      Yangtze River wild common carp and Xingguo red carp. Genetic distance analysis
      (Nei's standard genetic distance and pairwise F(st) distance) showed that the
      largest distance was between Russian scattered scaled mirror carp and the Yangtze
      River wild common carp and the smallest distance was between the Yangtze River
      wild common carp and Xingguo red carp. However, among six populations Japanese
      decorative carp displayed the highest level of variability in terms of
      heterozygosity.

PMID- 15575507
TI  - [Distribution of the HIV-1 resistance-conferring alleles (CCR5delta32, CCR2-64I,
      and SDF1 3'A) in Russian, Ukrainian, and Belarusian populations].
AB  - The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1 3'A, known to
      decrease the risk of AIDS onset and the rate of the disease progression in HIV
      infected individuals were determined in three native population samples from
      Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12,
      0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and
      Belarussians, respectively. The proportion of the individuals without any of
      three protective alleles among Russians, Ukrainians, and Belarussians constituted
      49, 65, and 61%, respectively. The genotype frequencies for the three loci
      studied were in Hardy-Weinberg equilibrium. Based on the three-locus genotype
      frequencies, the hazard ratios (relative hazards, RH) of AIDS onset in HIV
      infected individuals in each sample were calculated as ranging from 0.79 to 0.88.
      In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS
      protective alleles tested, as well as the frequencies of the corresponding
      genotypes and the relative hazards of AIDS onset were within the range of these
      parameters for the other European populations. The data on the allele frequencies
      and the relative hazard values in Russians, Ukrainians and Belarussians can be
      used as the predictors of AIDS onset and progression rate in HIV-1-infected
      individuals from the populations studied.

PMID- 15575508
TI  - [Association of polymorphic marker A1/A2 of gene ITGB3 with coronary artery
      disease and myocardial infarction].
AB  - The distributions of the alleles and genotypes of polymorphic marker A1/A2 of
      gene ITGB3 encoding the beta3 subunit of integrin alphaIIbbeta3 in groups of
      patients with coronary artery disease (CAD), including those who have had
      myocardial infarction (MI), and in the control group have been compared. Analysis
      using Fisher's test has not revealed significant differences between these groups
      with respect to the distributions of the alleles and genotypes of polymorphic
      marker A1/A2 of gene ITGB3. This indicates that this polymorphic marker is not
      associated with either CAD or MI in the Moscow population.

PMID- 15575509
TI  - [Association of polymorphic marker G(-455)A of gene FGB with coronary artery
      disease].
AB  - Patients with coronary artery disease (CAD), including those who have had
      myocardial infarction (MI), and control subjects have been compared with respect
      to the distributions of the alleles and genotypes of polymorphic marker G(-455)A
      of gene FGB encoding the fibrinogen beta-chain. The groups studied do not differ
      significantly with respect to the distributions of G(-455)A alleles and
      genotypes. This indicates that this marker is not associated with CAD in the
      Moscow population. Allele A of the G(-455)A polymorphic marker has been found to
      be associated with an increased fibrinogen content of blood plasma in women with
      CAD.

PMID- 15575510
TI  - [Analysis of the angiotensinogen gene T174M polymorphism in populations of the
      Volga-Ural region].
AB  - The method of polymerase chain reaction was used to analyze T174M polymorphism at
      the angiotensinogen (AGT) gene in a number of populations of the Volga-Ural
      region, belonging to Finno-Ugric (Komi-Permyaks, Maris, Mordovians, and Udmurts),
      Turkic (Chuvashes, Tatars, and Bashkirs), and Eastern-Slavic (Russians) ethnic
      groups. Population-specific patterns of the polymorphic alleles and genotypes
      frequency distribution were established. Comparison of the results with the
      literature data on the AGT gene polymorphism in different world populations
      provided identification of specific trends in the changes of genotype frequency
      of the AGT gene depending on the ethnicity of the populations.

PMID- 15575511
TI  - [Prevalence of hereditary pathology in Altai Republic].
AB  - Medical genetic study of the population of Altai Republic (Russia) has been
      performed. The population sample comprises 203 148 subjects, including 59 196
      Altaians, 134 972 Russians, and 8980 Kazakhs. For each nosological group, the
      loads of Mendelian pathology with different modes of inheritance and their
      prevalence rates in urban and rural populations have been determined. Thirty-six
      autosomal dominant (AD) diseases have been found in a total of 121 subjects, with
      hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology
      is represented by 24 diseases found in 158 subjects, with metabolic disorders
      being the most prevalent; and X-linked pathology, by four diseases in nine
      subjects. The prevalence rate has been calculated for each nosological form in
      the district where it has been found. The loads of AD, AR, and X-linked
      pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000
      people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23
      per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural
      population, the genetic load has been calculated for each district. The spectrum
      of hereditary pathology in the populations studied is described.

PMID- 15575512
TI  - [An algorithm of step-by-step pedigree drawing].
AB  - An algorithm for drawing large, complex pedigrees containing inbred loops and
      multiple-mate families is presented. The algorithm is based on a step-by-step
      approach to imaging, when the researcher determines the direction of further
      extension of the scheme. The algorithm is implemented as the PedigreeQuery
      software package written in Java. The software has a convenient graphical
      interface. The software package permits constructing not only whole pedigrees,
      but also their fragments that are particularly interesting for research. It also
      allows for adding new information on the phenotypes and genotypes of pedigree
      members. PedigreeQuery is distributed free of charge; it is available at
      http://mga.bionet.msc.ru/PedigreeQuery/PedigreeQuery.html and
      ftp://mga.bionet.msc.ru/PedigreeQuery/.

PMID- 15575513
TI  - [Variation in lengths of introns and exons in genes of the Arabidopsis thaliana
      nuclear genome].
AB  - In the nuclear genes of Arabidopsis thaliana, the length of introns and exons was
      shown to vary depending on the number of introns. With increasing number of
      introns per gene, the proportion of introns composed of 80-100 nucleotides
      increases whereas the proportion of introns with 400-nucleotide length decreases.
      Similar changes in exon length in genes result in predominance of exons of 60-120
      nucleotides in length.

PMID- 15575514
TI  - [RAPD fingerprinting of common bream Abramis brama L., roach Rutilus rutilus L.,
      and their F1 hybrids].
AB  - The polymerase chain reaction with arbitrary primers (RAPD-PCR) was used to study
      and to evaluate the genetic variation in the hybrid progeny of two Cyprinidae
      species, common bream Abramis brama and roach Rutilus rutilus. Genetic
      polymorphism was studied in 20 fishes (young of the current year) obtained in
      four individual crosses: R. rutilus x R. rutilus (RR), A. brama x A. brama (AA),
      R. rutilus x A. brama (RA), and A. brama x R. rutilus (AR). Amplification spectra
      obtained with eight primers contained 288 fragments, 97.6% of which proved to be
      polymorphic. The proportion of polymorphic fragments was 75.0% in the RR progeny,
      58.1% in the AA progeny, 84.9% in the AR progeny, and 77.8% in the RA progeny.
      Classification analysis in the space of principal components was performed with
      the first four components, which together accounted for 64% of the total variance
      of the character under study. The individual contributions of components I, II,
      III, and IV were 26.8, 16.8, 11.5, and 8.9%, respectively. Fishes of the two pure
      species and the hybrid progeny (direct and reverse hybrids together) were clearly
      differentiated in the space of principal components I and II. The best
      differentiation of the four samples (RR, AA, RA, and AR) was observed in the
      space of principal components II and IV. Possible causes of high genetic
      variation in interspecific hybrids are discussed.

PMID- 15575516
TI  - A call for policy action.

PMID- 15575515
TI  - [Geographical variation of allele frequencies at the LDH-A* locus in the arctic
      grayling Thymallus arcticus Pall. and in the European grayling Thymallus arcticus
      L].
AB  - The allele frequencies of LDH-A* locus were studied in the population of Siberian
      grayling from the Kozhym River (Pechora basin) and in the population of European
      grayling from Pechora, Mezen', and Vym' rivers (Northern Dvina basin). In samples
      of both species (n = 134), three LDH-A phenotypes have been identified in total,
      which proved to be under the control of two alleles: LDH-A*100 and LDH-A*50. The
      alternative alleles of LDH-A* locus were identified in the populations of
      Siberian grayling from Kozhym River and in the population of European grayling
      from the same river and other Pechora tributaries, namely, LDH-A*100 and LDH-A*50
      in the Siberian and the European grayling, respectively. However, in the European
      grayling populations from the Mezen' and Vym' rivers, both alleles occur at the
      frequencies of the rare LDH-A*100 allele of 0.143 and 0.222, respectively.
      According to the published data, the frequency of LDH-A*100 allele increases in
      the European grayling populations of northwestern (Finland) and southern (France)
      rivers, reaching 0.872 and 1.000 in Rhone and Loire, respectively, i.e., the
      values characteristic of the Siberian grayling populations.

PMID- 15575517
TI  - Promoting adherence, one patient at a time.

PMID- 15575518
TI  - Evidence-based strategies to foster adherence and improve patient outcomes.

PMID- 15575519
TI  - How effective communication promotes better health outcomes.

PMID- 15575520
TI  - A patient-centered approach to chronic disease management.

PMID- 15575521
TI  - Operational supports to improve adherence: strategies from the field.

PMID- 15575522
TI  - Dietary cactus reduces blood glucose levels in a Hispanic man.

PMID- 15575523
TI  - Current approaches preventing osteoporosis.

PMID- 15575524
TI  - A persistent auricular rash in a 12-year-old girl.

PMID- 15575525
TI  - Case of the month. Kartagener's syndrome.

PMID- 15575526
TI  - [Efficacy of climate therapy in patients with chronic cardiac failure at a
      climate-balneological resort].
AB  - The aim of our study was to estimate clinical effects of spa therapy (ST) at
      Sochi-Macesta resort in patients with heart failure (HF). Spa therapy was given
      to 116 patients with HF functional class (FC) 0-II by NYHA classification. It is
      shown that ST leads to improvement of the patients' clinical status, reduction of
      HF FC (from 1.32 +/- 0.09 to 0.66 +/- 0.01, p < 0.001), to increased exercise
      tolerance (p < 0.05) and better 6-minute walk test results (from 460.3 +/- 11.4 m
      to 511.2 +/- 11.8 m, p < 0.01), higher myocardial coronary reserve, favourable
      shifts in blood pressure. ST also has a cardiotonic effect and corrects
      vegetative status, there was also antiatherogenic effect and an increase in blood
      coagulation potential. The received data allow us to conclude that ST can be an
      effective tool of medical rehabilitation in patients with initial stages of heart
      failure.

PMID- 15575527
TI  - [Aromamassage of the cervical collar region in the combined treatment of patients
      with atherosclerotic dyscirculatory encephalopathy].
AB  - Aromamassage of the cervical color zone in 100 patients with atherosclerotic
      dyscirculatory encephalopathy resulted in a significant improvement of cerebral
      circulation and functional state of the brain.

PMID- 15575528
TI  - [Effects of carbon dioxide baths and exercise on physical performance of patients
      with left ventricular dysfunction after myocardial infarction].
AB  - Carbon dioxide baths (CDB) and exercise have a good effect on clinical indices of
      the postinfarction period in patients suffering from postinfarction
      cardiosclerosis with impaired left ventricular function, especially in combined
      use. Patients on general CDB and/or exercise exhibited a significant increase in
      time of exercise and power of the threshold load, less frequent occurrence of
      ischemic depression of ST segment and dyspnea in performing bicycle exercise. CDB
      and exercise are especially beneficial for patients with systolic dysfunction.

PMID- 15575529
TI  - [Effect of weather on a course of chronic obstructive pulmonary disease in
      conditions of the Northern Kirghizia with moderate continental climate].
AB  - A monitoring of clinical and functional conditions in different types of weather
      was made in 123 patients with chronic obstructive pulmonary disease living in
      North Kirghizia. It was found that unfavourable weather has a negative impact on
      clinical condition of the patients as well as their external respiration
      function. Parasympathetic effects enhance while pulmonary surfactant's activity
      weakens.

PMID- 15575530
TI  - [Efficacy of an autonomic electronic stimulator of the gastrointestinal tract in
      patients with chronic acalculous cholecystitis].

PMID- 15575531
TI  - [Differential health resort drinking treatment of patients with chronic
      pancreatitis].
AB  - Examination of 71 patients with chronic pancreatitis (CP) has revealed that such
      patients had subnormal levels of antiproteolytic enzymes even in pancreatitis
      remission. Compared to women, men had higher total cholesterol (by 12.2%),
      triglycerides (by 13.3%), LDLP (by 19.3%), respectively, while women had higher
      insulin (by 22%) and cortisol (by 13.4%). Glycemia was higher in men (by 10 and
      18% according to glucose tolerance test, min 30 and 60). The most effective spa
      regimen for CP patients was drinking mineral water from Slavyanovsky spring (56
      degrees C) in a half-dose and from the spring Vladimirsky (24 degrees C) in a
      standard dose. The standard dose of mineral water from Slavyanovsky mineral
      spring has the best effect in patients with carbohydrate metabolism disorders.

PMID- 15575532
TI  - [Natural and preformed physical factors in the treatment of late complications in
      diabetes mellitus type 2].

PMID- 15575533
TI  - [Health improving and rehabilitation techniques of using a water extract
      preparations made of deer antlers in chronic prostatitis].

PMID- 15575534
TI  - [Use of radon-containing rectal suppositories in chronic prostatitis complicated
      by sexual dysfunctions].
AB  - The article describes how to apply radon-containing rectal suppositories in
      patients with chronic prostatitis (CP). Intrarectal insertion of the
      suppositories is performed in the patients lying in the left lateral or knee
      elbow position daily for the first 8 days in a dose 18.5 kBk, for the following 2
      4 days in a daily dose 37 kBk 2-3 times a day. So, the course of the treatment
      takes 10-12 days. Such treatment of CP patients eradicated or alleviated
      prostatic inflammation and improved sexual function, was effective in 80%
      patients, prolonged remission to 12-16 months.

PMID- 15575535
TI  - [Electromagnetic fields of superhigh, extremely high frequencies and lipid
      peroxidation (an experimental study)].

PMID- 15575536
TI  - [The role of leukocytes in mechanism of action of balneopeloidotherapy].
AB  - Treatment with alkaline sulfide mud activates oxidant activity of neutrophils
      which stimulate body defense and adaptation but can provoke balneoreactions.
      Lysosomic membranes remain stable as mud does not stimulate phagocytosis. Peloid
      therapy stimulates a monocytic (macrophagal) lineage of hemopoiesis directed to
      elimination of intracellular microflora and products of inflammation. Radon
      therapy depresses oxidant and non-oxidant neutrophil activity thus diminishing
      damage to tissues and vessels and relieving inflammation.

PMID- 15575537
TI  - [Vibrovacuumtherapy in cellulitis].

PMID- 15575538
TI  - [Results of the combined treatment of chronic eye diseases in schoolchildren
      living in the Far North].

PMID- 15575539
TI  - [EHF-therapy in early rehabilitation of patients after surgical treatment of
      gastric and duodenal ulcer].

PMID- 15575540
TI  - [Therapeutic excercise in rehabilitation of patients with diabetes mellitus after
      lower limb amputation].

PMID- 15575541
TI  - [On osteochondrosis (comment on P. L. Zharkov's articles in "Voprosy
      kurortologii" journal N 2 and 6, 2003)].

PMID- 15575542
TI  - [Comment on the articles by V. A. Chelnokov "Interpretation of the current theory
      of spinal osteochondrosis pathogenesis in sporting medicine" published in the
      journal "Theory and Practice of Physical Culture" N 1, 2004 and by O.N. Markov
      "On osteochondrosis" published in the journal "Voprosy Kurortologii" N 5, 2004].

PMID- 15575543
TI  - [A. M. Ovchinnikov and his theory on deposits of mineral waters (the 100th
      anniversary of birth)].

PMID- 15575544
TI  - [V. D. Zipalov--one of the founders of clinical and experimental balneology].

PMID- 15575545
TI  - [Use of local low pressure in medicine. History and perspectives].

PMID- 15575546
TI  - Cholera, Liberia.

PMID- 15575547
TI  - WHO global conference on severe acute respiratory syndrome (SARS).

PMID- 15575548
TI  - Paths to sustainable procurement.
AB  - Every aspect of our environment can impact on our health, from air or water
      pollution to a healthy diet and a decent home. For example, in the UK up to
      24,000 vulnerable people are estimated to die prematurely each year because of
      exposure to air pollution, much of which is due to road traffic. How we feel
      about our immediate environment can affect our quality of life and sense of
      wellbeing. Crime, the fear of crime, social exclusion and environmental decline
      in a neighbourhood are all associated with increased burdens on mental health.

PMID- 15575549
TI  - Supporting vital infrastructure.
AB  - The past 20 years have seen a huge technological revolution, yet the associated
      electrical infrastructure within the hospital environment required to sustain
      critical operations has been slower to emerge.

PMID- 15575550
TI  - Methods to much improve maintenance.
AB  - The benefits to be gained from the application of both value engineering (VE) and
      quality systems--e.g. quality assurance (QA), and total quality management (TQM)-
      to the management of building services maintenance have yet to be realised by the
      building services industry. These concepts are particularly applicable to complex
      hospital engineering services.

PMID- 15575551
TI  - Alarm upgrade meets new standards.
AB  - When Bedford Hospital NHS Trust decided to replace its ageing and increasingly
      unreliable fire detection and alarm system, it was looking to achieve more than
      just compliance with the latest regulations. It wanted a flexible, state-of-the
      art system that would not only meet its current requirements but would also be
      easy to adapt and inexpensive to maintain. The pound 1 million Gent Vigilon fire
      system now operating across the site has given it just that. The 15-month long
      project to install the system was completed without a single ward or operating
      theatre having to be shut down.

PMID- 15575552
TI  - Preventing airborne contamination.
AB  - The air in a hospital contains a variety of contaminants originating from outdoor
      air, but also significant concentrations of compounds emitted indoors. All of
      these are transferred and distributed via the central heating, ventilation and
      air conditioning (HVAC) systems unless protective measures are taken.

PMID- 15575553
TI  - Systematic indoor risk management.

PMID- 15575554
TI  - Equipment life cycle costs minimised.
AB  - With the cost of energy now a major component of building operating costs, NHS
      Trust managers increasingly focus on estimating total life cycle costs of
      equipment such as boiler room and heat, steam and incineration plant. "Life cycle
      costing" is a broad term and encompasses a wide range of techniques that take
      into account both initial and future costs as well as the savings of an
      investment over a period of time.

PMID- 15575555
TI  - DEHP metabolites in urine of children and DEHP in house dust.
AB  - Urine samples from the 2001/2002 pilot study for the German Environmental Survey
      on children (GerES IV) were analysed for concentrations of the primary DEHP
      metabolite MEHP (mono(2-ethylhexyl)phthalate) and two secondary DEHP metabolites
      SOH-MEHP (2-ethyl-5-hydroxy-hexylphthalate) and 5oxo-MEHP (2-ethyl-5-oxo
      hexylphthalate). Urine samples had been taken from 254 children aged 3 to 14. In
      addition, DEHP was analysed in house dust samples. These samples had been
      collected with vacuum cleaners in the homes of the children. The geometric mean
      (GM) was 7.9 microg/l for MEHP in urine, and the GMs for the secondary
      metabolites 5OH-MEHP and 5oxo-MEHP were 52.1 microg/l and 39.9 microg/l. 5OH-MEHP
      and 5oxo-MEHP concentrations were highly correlated (r = 0.98). The correlations
      of 5OH-MEHP and 5oxo-MEHP with MEHP were also high (r = 0.72 and r = 0.70). The
      concentrations of 5OH-MEHP and 5oxo-MEHP were 8.0-fold and 6.2-fold higher than
      the concentrations of MEHP. The ratios 5OH-MEHP/Soxo-MEHP and 5oxo-MEHP/MEHP
      decreased with increasing age. Boys showed higher concentrations than girls for
      all three metabolites of DEHP in urine. Children aged 13-14 had the lowest mean
      concentrations of the secondary metabolites in urine. The house dust analyses
      revealed DEHP contamination of all samples. The GM was 508 mg/kg dust. No
      correlation could be observed between the levels of any of the urinary DEHP
      metabolites and those of DEHP in house dust.

PMID- 15575556
TI  - In-flight spraying in aircrafts: determination of the exposure scenario.
AB  - Exposure measurements were carried out in parked aircrafts during and after
      application of a biocide aerosol spray (simulated in-flight spraying). The
      aerosol product SRA spray (Standard Reference Aerosol Spray) was used for
      spraying. Concentrations of the pyrethrins--the active ingredients--in the air of
      the passenger cabin (airborne particles, measured during spray application and 40
      minutes afterwards) varied from 11 to 65 microg/m3; those of the synergist
      piperonyl butoxide were 200-485 microg/m3. The concentrations on surfaces of the
      cabin furniture differed widely. Low concentrations were determined on surfaces
      in vertical positions (median values: pyrethrins < or =2 ng/cm2; piperonyl
      butoxide < or =17 ng/cm2), while under seats, on seats and on headrests the
      concentrations were up to 55.5 ng/cm2 for pyrethrins and 1162.5 ng/cm2 for
      piperonyl butoxide (median values). The inhaled doses for sprayers (using 100 g
      of spray) and persons sitting in the passenger cabin were calculated to be 17
      microg for pyrethrins and 200 microg for piperonyl butoxide (maximum values).
      Maximum total external body doses for the applicators during spraying were 830
      microg for pyrethrins and 8840 microg for piperonyl butoxide. The potential
      dermal dose for persons sitting in the passenger cabin was about a factor of two
      lower.

PMID- 15575557
TI  - Blood lead levels of both mothers and their newborn infants in the middle part of
      China.
AB  - A cross-sectional investigation on maternal and umbilical blood lead levels in an
      urban area, an industrial town and a rural area of middle China is reported.
      Blood samples from 89 mothers during delivery, from the umbilical cords and from
      105 non-pregnant women were collected. Self-administered questionnaires including
      the medical history and the pregnancy-related complaints were performed. After
      acid digestion, the whole blood lead levels were determined by a 180-80 flame
      atomic absorption spectrometer. The geometric mean for lead levels in blood of
      non-pregnant women was 66.9 microg/l (range: 25.0-201.0 microg/l) in the urban,
      66.9 microg/l (range: 30.5-198.8 microg/l) in the industrial town, and 53.3
      microg/l (range: 16.0-170.5 microg/l) in the rural area. The geometric mean of
      lead levels in blood of pregnant women at delivery both in the rural area (74.4
      microg/l, range: 35.2-245.6 microg/l) and industrial town (65.9 micro/l, range:
      20.0-172.0 microg/l) were higher than in the urban region (54.3 microg/l, range:
      27.9-187.0 microg/l; p < 0.05). Compared with non-pregnant women at the same
      area, the blood lead levels of pregnant women was lower in urban (p < 0.05), but
      higher in rural areas (p < 0.05). The geometric mean for lead level in umbilical
      cord blood was significantly higher in rural (84.1 microg/l, range: 28.0-185.0
      microg/l) than in the other areas (53.5 microg/l, range: 23.5-156.7 microg/l in
      the urban; 60.1 microg/l, range: 12.5-168.3 microg/l in the industrial town). The
      total geometric mean for lead level in cord blood was 69.0 microg/l (range: 12.5
      185.0 microg/l), and 17.8% samples were above the blood lead threshold of health
      concern (> or =100 microg/l) for children (CDC, 1991), but the body weight and
      length of newborn babies have not been affected. The correlation between maternal
      and cord blood was 0.6805 (p < 0.01). Most of the pregnant women did not take the
      calcium supplements recommended during pregnancy. In conclusion, there were some
      lead burdens on both the mothers and their newborn babies in these areas. All
      possible measures should be taken to reduce the environmental lead exposure. It
      is also crucial that maternal nutrient intake, particularly calcium, should be
      sufficient.

PMID- 15575558
TI  - Preschool children's lead levels in rural communities of Zhejiang province,
      China.
AB  - The aim of the study was to determine mean blood lead levels (BLLs) and
      prevalence of elevated BLLs among preschool children aged 3-6 years in Zhejian
      rural communities, China. Data were gathered by means of a questionnaire and
      blood lead analyses for 217 children who attended six randomly selected
      kindergartens. BLLs ranged from 25-437 microg/l. Arithmetic mean was 95 microg/l
      and standard deviation was 56 microg/l. BLLs of 63 samples (29.0%) were > or =100
      microg/l. Children with BLLs > or =100 microg/l came from families with a higher
      proportion of their fathers or mothers working in conditions of potential
      exposure to lead, as compared to those with BLLs <100 microg/l (P < 0.01). A
      significantly higher proportion of children with BLLs > or =100 micro/l lived in
      buildings that were located near small industries, such as mechanics, furniture,
      or paint shop, as compared to those with BLLs <100 microg/l (P < 0.01). In
      conclusion, the data indicate that high levels of childhood lead exposures even
      prevail in rural communities and deserve authorities' attention. With the recent
      ban of leaded gasoline in China, emphasis should shift to other sources of
      exposure in children.

PMID- 15575559
TI  - Pilot study on the naphthalene exposure of German adults and children by means of
      urinary 1- and 2-naphthol levels.
AB  - Concentrations of 1- and 2-naphthol were measured in urine of 72 adults and 35
      young children from Germany to assess the internal exposure to naphthalene of the
      general population. Naphthols could be detected in more than 90% of the urine
      samples. Levels of naphthols (sum of 1- and 2-naphthol) were 4-fold higher in
      smokers (median: 37.6 microg/g creatinine) compared to non-smoking adults (8.2
      microg/g creatinine). On a creatinine basis young children had slightly lower
      naphthol levels in urine compared with adults (7.5 microg/g creatinine).
      Preliminary reference values for the sum of 1- and 2- naphthol in urine as means
      of the 95th percentile are proposed: 41.2 microg/g creatinine (non-smoking
      adults) and 23.5 microg/g creatinine (young children). It is concluded that 1-
      and 2-naphthol levels in urine are suitable for human biomonitoring of the
      naphthalene exposure in environmental medicine.

PMID- 15575560
TI  - Peri-urbanization and in-home environmental health risks: the side effects of
      planned and unplanned growth.
AB  - Urbanization is occurring at an explosive rate, and many cities, especially in
      low-income countries, are struggling to control growth and stop the development
      of unplanned communities. This research investigates the in-home environmental
      health risks associated with planned and unplanned growth in peri-urban
      communities (neighborhoods) of a rapidly growing city in Northern Mexico. Surveys
      were conducted during home visits to 98 households in a planned community and 202
      households in unplanned communities of comparable, though slightly higher, socio
      economic status. To assess the differences for the two types of communities,
      multiple risk factors were measured and compared. Results showed that households
      in both planned and unplanned communities were vulnerable to poor environmental
      health conditions, but more risk factors and negative health outcomes were
      associated with unplanned communities. Some of the obvious benefits of living in
      a planned community included better-constructed homes and water and sewer
      connections. Other study results indicated that households in the planned
      community reported fewer cases of respiratory problems (P = 0.039) and dizziness
      (P = 0.009). They were also less likely to store insecticides and other chemicals
      inappropriately in their home (P < 0.001). Providing adequate housing
      infrastructure appears to provide a number of important benefits to health and
      behavior beyond the simple provision of additional amenities in the home.

PMID- 15575561
TI  - Antioxidant response at early stages and low grades of simple coal worker's
      pneumoconiosis diagnosed by high resolution computed tomography.
AB  - In miners exposed to coal dusts, coal worker's pneumoconiosis (CWP) can occur.
      The purpose of the present study is to better understand the relations between
      coal dust exposure and activities of blood plasma antioxidant enzymes, namely,
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid
      peroxidation end product malondialdehyde (MDA) concentration in coal workers with
      early and low grade simple CWP diagnosed by high resolution computed tomography
      (HRCT). Forty-three coal workers who had profusions of 0/1-2/2 according to ILO
      1980 chest X-ray (CXR) classification, 43 coal workers without CWP (control group
      1) and 44 healthy subjects (control group 2) who were randomly selected from the
      population register or recruited from the hospital staff were enrolled. Coal
      workers were reevaluated by HRCT (Hosoda-Shida classification) due to its higher
      sensitivity than standard CXR. Then, blood plasma SOD and GSH-Px activities and
      MDA plasma levels were measured. CWP was found positive in 46 of 89 coal workers
      by HRCT evaluation. Profusion 0 (P0, CWP not present), profusion 1 (P1, early
      CWP) and profusion 2 (P2, low grade CWP) were found in 43, 23 and 19 of patients
      found to have CWP by HRCT, respectively. We had no worker with profusion 3 (P3).
      Complicated CWP was shown in four of 46 patients and thesecases were excluded as
      the study was restricted to early and low-grade pneumoconiosis. In respect to the
      plasma levels of MDA and plasma activities of SOD and GSH-Px, statistically
      significant differences were found between CWP cases and control groups (p <
      0.01, p < 0.01, p < 0.001 respectively). Statistical differences were also
      obtained for the plasma activities of SOD and GSH-Px and levels of MDA in
      relation to HRCT profusions (p < 0.05). In conclusion, these findings suggest an
      oxidative stress due to increased free radicals and reactive oxygen metabolite
      production in early stages and low grades of simple CWP diagnosed by HRCT.

PMID- 15575562
TI  - Estimation of the dietary intake of acrylamide by German infants, children and
      adolescents as calculated from dietary records and available data on acrylamide
      levels in food groups.
AB  - Dietary intakes of acrylamide for the general population were estimated by
      FAO/WHO to be in the range of 0.3 to 0.8 microg/(kg(bw) *d). It was supposed that
      children and adolescents would generally have intakes twice to three times higher
      than adults. However, relevant data is rare. Therefore, 3- or 7-day dietary
      records (n = 2956) from infants, children and adolescents aged 0.5 to 18 years
      from the DONALD study (2001) and other studies (RUB studies) were evaluated to
      estimate the potential dietary intake of acrylamide. Statistical data of the
      intake of 6 food groups relevant for acrylamide exposure were combined with
      available data for ranges of acrylamide concentrations in more than 1500 foods in
      Germany. Scenarios were calculated assuming minimum, median and maximum
      acrylamide concentration in food groups. Assuming median (minimum; maximum)
      acrylamide concentrations in foods and mean consumed food amounts, the calculated
      intake of acrylamide ranged from 0.21-0.43 (0.12-0.19; 0.98-1.79) microg/(kg(bw)
      *d) between the age groups from <1 to <19 years in the DONALD study and was 0.61
      (0.21; 2.58) microg/(kg(bw) *d) from 1 to <7 years in the RUB studies. The
      highest intake was calculated for children aged 1-<7 years. The highest
      proportions of total intake of acrylamide came from the intake of commercial baby
      food (86-91%) in infants, and bread (18-46%), pastries (16-35%), and potato
      products (7-35%) in children and adolescents, depending on scenario and age. Our
      estimated data are in the range of reports from the literature for adolescents
      and adults in Germany and other European countries and lower than reports for
      infants. Our results do not confirm that children and adolescents will have
      higher exposures to acrylamide than adults. Practical suggestions to lower the
      risk of acrylamide exposure by food without decreasing the quality of the
      nutrition in the diet are given.

PMID- 15575563
TI  - Water contamination in urban south India: household storage practices and their
      implications for water safety and enteric infections.
AB  - Water contamination, at source and during household storage, is a major cause of
      enterically transmitted infections in developing countries. This study assessed
      contamination of the municipal water in a south Indian town, which obtains its
      water intermittently from a surface lake and by pumping subsurface water from a
      dry river bed, and monitored microbial contamination during household storage.
      All samples of the 'treated' municipal water were contaminated when freshly
      pumped, and on household storage, 25/37 (67%) showed increased contamination
      during storage periods from 1 to 9 days. Household storage in brass, but not in
      containers of other materials significantly decreased contamination of water (p =
      0.04). This was confirmed in the laboratory by testing water seeded with 10(3) to
      10(5) Escherichia coli per 100 ml stored in containers of different materials (p
      < 0.01). Despite the requirements for provision of safe drinking water in
      municipal areas, in practice the water supplied in Vellore is contaminated and
      current household storage practices increase the level of contamination in at
      least two-thirds of households. The implementation of locally appropriate point
      of-use disinfection and safe household storage practices in developing countries
      is an urgent need to ensure a safe, reliable year-round supply in areas where
      clean water is not available.

PMID- 15575564
TI  - Semmelweis' legacy: insights from an international survey among 265,000 students
      in 32 countries.
AB  - The Programme for International Student Assessment (PISA) 2000 study assessed a
      wide range of knowledge and skills attained by 265,000 15-year-olds in 32
      industrialized countries. One survey unit of the scientific literacy section
      addressed infection control issues, based on Semmelweis' landmark research on the
      causes and prevention of puerperal fever. The present report describes the
      questions and student performance for this infection control exercise set and
      evaluates performance variability between countries.

PMID- 15575565
TI  - Life, epidermolysis bullosa and chasing tornadoes.
AB  - Sam Hall was diagnosed with epidermolysis bullosa as a baby. Here she describes
      growing up with the condition and the continual dressing changes it brings, and
      how she has not let it prevent her from leading an active and exciting life.

PMID- 15575566
TI  - The importance of pain reduction through dressing selection in routine wound
      management: the MAPP study.
AB  - OBJECTIVE: To discover the incidence of pain in patients with acute or chronic
      wounds of various causes during dressing removal, and the effect of switching to
      a non-adherent dressing. METHOD: A total of 656 primary care physicians reported
      the relevant details of all acute or chronic wounds observed during routine
      visits throughout the study period. The pain experienced during dressing changes
      was systematically evaluated. In patients with moderate to severe pain, a more
      extensive evaluation was performed and they were invited to complete a self
      evaluation questionnaire. If the patients were seen at a subsequent visit, a new
      evaluation was performed. RESULTS: In total 5850 patients were seen: 2914 with
      acute wounds and 2936 with chronic wounds. During dressing changes, a similar
      number of patients with acute and chronic wounds reported 'moderate to severe'
      pain during the medical screening visit (79.9% and 79.7%) and 'very severe' pain
      in their self-evaluation questionnaire completed at home (47% and 59%
      respectively). Dressing removal was most painful when there was adherence to the
      wound bed. Switching to a new, non-adherent dressing reduced pain during dressing
      changes in 88% of patients with chronic wounds and 95% of patients with acute
      wounds. CONCLUSION: This study demonstrates that similar problems with patient
      acceptability arise irrespective of wound aetiology. Pain is a major problem and
      is most often related to dressing selection. Selecting a suitable, non-adherent
      dressing improves patient acceptability.

PMID- 15575567
TI  - Antimicrobial textiles.

PMID- 15575568
TI  - Topical PDGF-BB results in limited healing in a patient with Werner's syndrome
      and chronic leg ulcers.
AB  - Impaired wound healing is a feature of Werner's syndrome. Treatment of one such
      patient with painful chronic leg ulcers included topical application of PDGF-BB.
      Granulation increased slightly, enabling full-thickness skin grafting to take
      place.

PMID- 15575569
TI  - Effects of an activated charcoal silver dressing on chronic wounds with no
      clinical signs of infection.
AB  - OBJECTIVE: This exploratory, clinical study aimed to explore the effect of an
      activated charcoal silver dressing (intervention) with cleansing and debridement
      (control) in reducing the level of bacteria in chronic wounds with no clinical
      signs of local infection. METHOD: Patients were randomly assigned to the
      intervention or control group and monitored for two weeks. Samples for bacterial
      status and cultivation were obtained by surface smear (spatula) and percutaneous
      aspiration first at baseline and then after 15 days of treatment. Sixty-seven
      lesions were included in the intervention group and 58 in the control group.
      RESULTS: At baseline, in the intervention group 71.6% of the wounds were
      contaminated, 7.5% had a high level of bacteria and 20.9% were infected. In the
      control group at baseline 65.5% of the wounds were contaminated, 6.9% colonised,
      6.9% had a high level of bacteria and 20.7% were infected. There were no
      colonised wounds in the intervention group. After two weeks, combining totals of
      contaminated, colonised, a high level of bacteria and infection for each group,
      85.1% (57/67) of the wounds in the intervention group had a positive bacterial
      level management (that is, a reduction in the number of bacteria in the wound)
      compared with 62.1% (36/58) in the control group (p=0.003). CONCLUSION: Activated
      charcoal dressings that contain silver control infection and reduce healing
      times, eliminating bacterial barriers.

PMID- 15575570
TI  - The effects of Panafil when using topical negative pressure to heal an infected
      sternal wound.
AB  - A wound that became infected a few weeks after bypass surgery responded well to a
      treatment regimen combining TNP with application of an enzymatic agent. The
      patient had diabetes mellitus, which slows healing and increases infection risk.

PMID- 15575571
TI  - Getting the record straight: the need for accurate documentation.
AB  - Complaints may end up being reviewed by the ombudsman. These cases usually have
      three things in common: poor communication, poor documentation and a failure to
      involve the practitioner concerned in the initial investigation.

PMID- 15575572
TI  - Developing a clinical risk management strategy.
AB  - The nature of most wound-care treatments makes clinical risk inevitable.
      Nevertheless, practitioners can do much to protect themselves. Mark Elster and
      Lorraine Grothier outline four key measures that will help them do this.

PMID- 15575573
TI  - Accountability and responsibility.
AB  - What can you do if the most appropriate treatment does not comply with a
      guideline, policy or procedure? A tissue viability team was faced with this
      dilemma when considering treatment options for an open wound in a woman with
      cancer.

PMID- 15575574
TI  - The role of the expert witness.
AB  - Juries do not have extensive health-care knowledge, so expert witnesses are
      needed to explain standards of care. Here, expert witness Sylvie Hampton
      describes this role and how these witnesses participate in court proceedings.

PMID- 15575575
TI  - Should ABPI be measured in patients with healed venous leg ulcers every three
      months?
AB  - OBJECTIVE: To assess if three-monthly reassessment of ABPI is necessary and to
      determine the possibility of identifying which patients may benefit from more
      frequent reassessment. METHOD: The sample comprised 88 consecutive patients with
      175 limbs attending community leg ulcer clinics for reassessment after leg ulcer
      healing had been achieved with compression therapy. Outcome measures were: a fall
      in ABPI to below 0.8, months between reassessments and arterial disease history.
      RESULTS: ABPI fell from above 0.8 to below 0.8 in seven limbs in six patients
      over time periods of between six and 24 months. Of these seven limbs, six had an
      ABPI between 0.8 and 1.0 at the initial assessment, indicating they had some
      arterial impairment. ABPI fell below 0.7 (0.58) in only one patient, and this was
      detected at a six-month reassessment. None of the patients with no or just one
      arterial symptom experienced a reduction in ABPI to below 0.8. Those whose ABPIs
      fell below this level had two or more arterial symptoms. CONCLUSION: Three
      monthly reassessment of healed limbs is not recommended as most patients who
      initially have an ABPI above 1.0 are unlikely to change during this time.
      However, patients with two or more arterial risk factors, diabetes and an initial
      ABPI of below 1.0 are likely to need closer monitoring. More in-depth research is
      needed to examine this problem.

PMID- 15575576
TI  - Patient involvement must be a key aspect of choosing an appropriate regimen for
      leg ulcer management.
AB  - The final article in a six-part series on leg ulcers focuses on developing leg
      ulcer services in the community and stresses the importance of taking a holistic
      approach and the value of patient/carer education to promote concordance.

PMID- 15575577
TI  - The diagnosis and treatment of carcinomas occurring at the sites of chronic
      pressure ulcers.
AB  - Tumours that develop at the sites of pressure ulcers are very aggressive. Removal
      is thus crucial, but such cases are difficult to diagnose. This paper discusses a
      rare case of Marjolin's ulcer, which was treated with excision and radiotherapy.

PMID- 15575578
TI  - Use of medical honey in patients with chronic venous leg ulcers after split-skin
      grafting.
AB  - OBJECTIVE: To assess the use of medical honey on healing times and complications
      in patients with venous leg ulcers after split-skin grafting. METHOD: Healing
      time and morbidity were evaluated in six patients with chronic venous leg ulcers
      who underwent split-skin grafting followed by the application of medical honey at
      the vascular unit of University Hospital Aintree in Liverpool. RESULTS: Mean
      healing time was 22 days. There were no complications. CONCLUSION: The use of
      medical honey in patients who have received split-skin grafts for chronic venous
      leg ulcers appears to give a similar healing time to that seen without the
      application of honey. There were no major complications. Larger prospective
      randomised controlled trials are needed to confirm the findings.

PMID- 15575580
TI  - Spot the difference. The revised draft Mental Health Bill has been given a
      unanimous thumbs down.

PMID- 15575581
TI  - Black to black. A new national network for black and minority ethnic mental
      health aims to keep the issue high on the government's agenda.

PMID- 15575582
TI  - Staying connected. Mental Health Today exhibition and seminar.

PMID- 15575583
TI  - Learning to feel. New treatment for borderline personality disorder.

PMID- 15575584
TI  - Causes and consequences. Why are our psychiatric wards disproportionately
      populated by the poorest people?

PMID- 15575585
TI  - The high price of poverty. Poverty and debt are major risk factors for mental ill
      health in deprived communities and groups.

PMID- 15575586
TI  - Tackling the root cause. There are clear links between racism and the higher
      rates of mental illness among ethnic minority groups.

PMID- 15575587
TI  - You are where you live. Evidence shows that where we live has a significant
      impact on our mental health.

PMID- 15575588
TI  - Validation of electrochemical determination of zinc in selected pharmaceutical
      preparations.
AB  - A procedure of voltammetric (DP) determination of zinc in two selected
      pharmaceutical preparations was validated. The source of zinc in the first of
      them (Bio-Cynk) was the organic salt-gluconate, while the second (Zincteral)
      contained zinc sulfate. In order to transform zinc into solution, the samples of
      powdered tablets of each preparation underwent the extraction or mineralisation
      procedure. The concentration of zinc in solution was determined by differential
      pulse voltammetry (DP). In the validation process, the selectivity, accuracy,
      precision and linearity of DP determination of zinc in both preparations were
      examined. Zinc was determined within the concentration range of 1-20 ppm: the
      mean recoveries approached 98% in the case of Bio-Cynk and 100% for Zincteral;
      the errors of determination (RDS) were 2.98-11.5% for Bio-Cynk and 3.06-5.32% for
      Zincteral, respectively.

PMID- 15575589
TI  - The chromatographic data in QSAR assay of TIQs derivatives with beta2-adrenergic
      activity.
AB  - We performed QSAR analysis of beta2-adrenergic activity and chromatographic data
      of 4,6,8-trihydroxy-, 6,7-dihydroxy- and 6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline derivatives. TLC plates (silica gel NP 60F(254) and silica
      gel RP2 60F(254) silanised precoated), impregnated with solutions of analogues of
      the selected amino acids were used as beta2-agonistic and antagonistic
      interaction models. QSAR analysis of the beta2-adrenergic activity and the
      chromatographic data of the solutes were made. A correlation between biological
      data and behaviour of the examined compounds in a chromatographic modifiable
      environment (S1-S3) was investigated by the linear regression analysis method.

PMID- 15575590
TI  - Effect of cation content of certain ammoniomethacrylate copolymers type A (RL)
      and B (RS) on their binder property in tableting.
AB  - Tablets of salicylic acid (drug model) have been formed using two analogous
      acrylatemethacrylate copolymers designated here as A and B as binders. A and B
      differ only in their content of quaternary ammonium (cationic) groups in the
      ratio 2:1 (A:B). The aim was to investigate the effect of the cationic groups on
      the tableting characteristics of the formed granules. In the procedure, aqueous
      dispersions of the polymers of concentrations 1 to 5% w/v were used in a separate
      experiment for granulation of the salicylic acid powder and then tableted. The
      final concentration of the binder in the tablets varied from 0.4 to 2% w/w. The
      parameters assessed were the tablet tensile strength (T) and their brittle
      fracture index (BFI) which are indicative of the plasto-elasticity of the
      granules; for instance, a high T value together with a low BFI value are
      indicative of a high plasto-elasticity. A and B generally displayed a strong
      binder property as they individually produced hard tablets even at the low
      concentration 0.4% w/w. As the binder concentration in the tablets increased to
      2% w/w. tensile strength (MNm(-2)) increased from 1.08 to 1.80 (tablets of
      polymer A), 1.08 to 2.02 (tablets of polymer B). BFI values decreased from 0.24
      to 0.06 (tablets of polymer A) and 0.16 to 0.04 (tablets of polymer B). These
      results indicate that the presence of the cationic groups in the polymer
      structure promoted elastic rather than plastic compression.

PMID- 15575591
TI  - Anti-tuberculosis activity of some N-pentopyranosylamines.
AB  - With the advent of multidrug-resistant Mycobacterium tuberculosis, new effective
      drugs are rapidly needed. Thirty-two derivatives of some N-pentopyranosylamines
      were prepared and tested under the Tuberculosis Antimicrobial Acquisition and
      Coordinating Facility (TAACF) program. This communication is presenting their
      antituberculosis activity in the primary screen.

PMID- 15575592
TI  - Stability of two new anticonvulsants in body fluids and tissues.
AB  - Stability of two compounds with established anticonvulsant activity, picolinic
      acid benzylamide (Pic-BZA) and nicotinic acid benzylamide (Nic-BZA), incubated in
      homogenates of body organs and in body fluids was determined at different time
      points. Pic-BZA was found to decompose fairly rapidly in the liver and the
      kidney, while Nic-BZA demonstrated stability against enzymes present in these
      organs and fluids.

PMID- 15575593
TI  - The content of lignan glycosides in Forsythia flowers and leaves.
AB  - Quantitative determination of lignan glucosides in flowers and leaves of three
      taxons of Forsythia Vahl was performed using the HPLC method. The main lignan
      compound in the flowers of F. suspensa appeared to be (+)-pinoresinol beta-D
      glucopyranoside, whereas in the leaves of this species phillyrin was the
      predominant lignan. The content of (+)-pinoresinol beta-D-glucopyranoside in F.
      suspensa flowers amounted to 4.3-7% and that of phillyrin did not reach 1%. The
      inverse ratio of (+)-pinoresinol beta-D-glucopyranoside to phillyrin occurred in
      the leaves of F. suspensa, which contained up to 4.3% of phillyrin and 1.6% and
      less (+)-pinoresinol beta-D-glucopyranoside. The flowers of F. viridissima and F.
      x intermedia were rich in arctiin: 5.5-10.2% and up to 11.5%, respectively. The
      leaves of these two species contained less arctiin: up to 4.3% in F. viridissima
      and up to 2.3% in F. x intermedia. The flowers showed the highest level of
      lignans at the phase of buds, it decreased during the blooming time.

PMID- 15575594
TI  - Anti-angiogenic activity of convallamaroside, the steroidal saponin isolated from
      the rhizomes and roots of Convallaria majalis L.
AB  - Angiogenesis plays a pivotal role in tumor growth and represents a key target for
      chemopreventive intervention. Despite the large number of existing angiogenesis
      inhibitors, there is still a great demand for new anti-angiogenic compounds. The
      objective of this study is to investigate the effect of administration of
      convallamaroside, a steroidal saponin isolated from the lily of the valley
      (Convallaria majalis L.) to mice on tumor angiogenesis reaction induced by tumor
      cells. Angiogenic activity was evaluated by mice intradermal test.
      Convallamaroside showed a significant inhibitory effect on the number of new
      vessels induced in mice by human kidney tumor cells (p < 0.001). Similarly,
      administration of convallamaroside to mice decreased the number of new vessels
      induced by sarcoma mice cells (p < 0.001).

PMID- 15575595
TI  - Restoration of antioxidants by ethanolic Tinospora cordifolia in alloxan-induced
      diabetic Wistar rats.
AB  - The present study investigates the effect of oral administration of an alcoholic
      extract of Tinospora cordifolia roots on antioxidant defence in alloxan-induced
      diabetes in rats. A significant increase in the concentration of thiobarbituric
      acid reactive substances (TBARS) in brain along with a decrease in heart was
      observed in diabetic rats. Decreased concentration of glutathione (GSH) and
      decreased activities of superoxide dismutase (SOD), catalase and glutathione
      peroxidase (GPx) in heart and brain of diabetic rats were also noted. Alcoholic
      Tinospora cordifolia root extract (TCREt) administered at a dose of 100 mg/kg to
      diabetic rats orally for six weeks normalized the antioxidant status of heart and
      brain. The effect of T. cordifolia root extract was more prominent than
      glibenclamide (600 microg/kg). Insulin (6 units/kg) restored all the parameters
      to normal status.

PMID- 15575596
TI  - In vivo study of angiogenic plasmid preparations--the bicistronic plasmid as a
      new type of drug for vascular diseases.
AB  - Angiogenic gene therapy is thought to be a new method for the treatment for
      vascular diseases. Plasmid preparations encoding angiogenic factors like a
      vascular endothelial growth factor (VEGF) or a fibroblast growth factor (FGF)
      effectively stimulate the formation of new vessels. The first clinical trials
      with novel angiogenic drugs--genetic preparations have already been reported.
      Nevertheless, gene transfer and expression efficiency still require a lot of
      experimental work. Here, three different angiogenic preparations were studied. We
      used monocistronic vectors encoding VEGF165 or FGF-2 and bicistronic construct
      expressing both of them. The angiogenic potency of the plasmids was evaluated by
      in vivo angiogenesis tests. We also tested the plasmid DNA maintenance in mouse
      tissue as well as the transcriptional activity of the angiogenic preparations. We
      saw that all plasmids effectively stimulate the formation of new vessels in in
      vivo conditions up to 20 days. The most powerfull angiogenic potency was
      demonstrated by the bicistronic vector. It was shown that after 3, 13, 21, 31 and
      41 days post-transfection the plasmid DNA still persisted in tissue, more or less
      on the same level but the mRNA transcripts after 13 days slowly decreased. This
      work confirmed effectiveness of gene therapy, and gave new information about
      angiogenic plasmid preparations useful for practical applications.

PMID- 15575597
TI  - New nucleoside analogs in the treatment of solid tumors.
AB  - Physiologic deoxynucleotides are required for an error-proof DNA replication,
      repair and synthesis. Any inaccuracy in this process results in a block in DNA
      synthesis until the error is corrected. If the cell enzymes are unable to correct
      the error, a signal for apoptosis is generated. This mechanism is the main target
      for anticancer nucleoside analogs. They also interact with the metabolism of
      physiological nucleosides, and consequently, have a large number of intracellular
      targets to induce cytotoxicity. In addition, it is now reported that some analogs
      may interfere directly with RNA synthesis. A great deal of synthesized nucleoside
      analogs provide the opportunity to understand the structure-based differences in
      their metabolism and mechanisms of action as well as to identify the specific
      intracellular targets and diseases, in which each of these newer nucleoside
      analogs acts most efficiently. This paper summarizes developments in the area of
      new nucleoside analogs undergoing clinical evaluation for the treatment of solid
      tumors, namely tezacitabine, troxacitabine, DMDC, CNDAC, ECyD, clofarabine, and
      decitabine.

PMID- 15575598
TI  - E- and Z-p-methoxycinnamic acid from Aquilegia vulgaris.
AB  - Two isomers E- and Z-p-methoxycinnamic acid were isolated from the leaves with
      stems of A. vulgaris L. and their structures were determined by 1HMR and 13C NMR
      spectral data.

PMID- 15575599
TI  - Application of copper (II) in spectrophotometric determination of some drugs of
      aliphatic amine nature.
AB  - Anhydrous copper(II) acetate was applied to spectrophotometric determination of
      amitriptilline, doxepin and lignocaine in acetone solutions. The developed method
      was employed for determining these substances in pharmaceutical preparations. The
      obtained results has indicated both high precision and accuracy of the method.

PMID- 15575600
TI  - The invertebrate deuterostomes: an introduction to their phylogeny, reproduction,
      development, and genomics.

PMID- 15575601
TI  - Care and maintenance of adult echinoderms.

PMID- 15575602
TI  - Echinoderm eggs and embryos: procurement and culture.
AB  - The protocols outlined here hopefully will provide researchers with healthy,
      beautiful echinoderm oocytes, eggs, and embryos for experimental use. The large
      size of echinoderm oocytes and eggs, the ease with which they can be manipulated,
      and (in many species) their optical clarity, make them an ideal model system for
      studying not only the events specific to oocyte maturation and fertilization, but
      also for investigating more general questions regarding cell cycle regulation in
      an in vivo system. The quick rate at which development proceeds after
      fertilization to produce transparent embryos and larva makes the echinoderm an
      advantageous organism for studying deuterostome embryogenesis. Continued use of
      the echinoderms as model systems will undoubtedly uncover exciting answers to
      questions regarding fertilization, cell cycle regulation, morphogenesis, and how
      developmental events are controlled.

PMID- 15575603
TI  - Culture of echinoderm larvae through metamorphosis.

PMID- 15575604
TI  - Obtaining and handling echinoderm oocytes.

PMID- 15575605
TI  - Procurement and culture of ascidian embryos.

PMID- 15575606
TI  - Culture of adult ascidians and ascidian genetics.

PMID- 15575607
TI  - Hemichordate embryos: procurement, culture, and basic methods.

PMID- 15575608
TI  - Cephalochordate (amphioxus) embryos: procurement, culture, and basic methods.

PMID- 15575609
TI  - Quantitative microinjection of oocytes, eggs, and embryos.

PMID- 15575610
TI  - Blastomere isolation and transplantation.

PMID- 15575611
TI  - Isolation and culture of micromeres and primary mesenchyme cells.

PMID- 15575612
TI  - Rapid microinjection of fertilized eggs.

PMID- 15575613
TI  - Methods for embryo dissociation and analysis of cell adhesion.

PMID- 15575614
TI  - Analysis of sea urchin embryo gene expression by immunocytochemistry.

PMID- 15575615
TI  - Light microscopy of echinoderm embryos.

PMID- 15575616
TI  - TEM and SEM methods.

PMID- 15575617
TI  - Calcium imaging.

PMID- 15575618
TI  - Labeling of cell membranes and compartments for live cell fluorescence
      microscopy.

PMID- 15575619
TI  - Isolation of organelles and components from sea urchin eggs and embryos.

PMID- 15575620
TI  - Sea urchin spermatozoa.

PMID- 15575621
TI  - Measuring ion fluxes in sperm.

PMID- 15575622
TI  - Isolating DNA, RNA, polysomes, and protein.

PMID- 15575623
TI  - Detection of mRNA by in situ hybridization and RT-PCR.

PMID- 15575624
TI  - Using reporter genes to study cis-regulatory elements.
AB  - This chapter summarizes four powerful assays for analyzing gene expression in cis
      regulatory studies. The enzymatic assays (CAT, luciferase, lacZ) are currently
      limited by their application to embryo homogenates or fixed samples, but offer
      more robust analysis of gene activity than GFP. Assays based on CAT enzymatic
      activity or on CAT mRNA detection by WMISH are laborious but are well established
      for accurately quantifying gene expression and to determine spatial patterns at
      defined timepoints during development. LacZ assays are the current standard for
      spatially visualizing gene products in whole-mount fixed embryos. They are very
      sensitive but they provide limited temporal or quantitative information due to
      the perdurance of beta-galactosidase and the subtleties of the staining
      technique. Recently developed luciferase assays promise to be even more sensitive
      and accurate than the CAT and lacZ assays, and applicable to living cells and
      embryos. But, they have not yet been well established in invertebrate
      deuterostome research. GFP allows visualization of gene expression within living
      embryos. But because this is not an enzymatic assay, sensitivity can be a
      problem, particularly for weak promoters. Furthermore, imaging live embryos and
      quantifying gene expression in space and time (due to scattering of light by
      tissue, the perdurance of GFP, and other experimental details) is currently
      fraught with challenges. Ongoing improvements in imaging technology and the
      advent of multiple fluorescent proteins, as well as fluorescent and luminescent
      assays for vital imaging, will dramatically facilitate studies of gene expression
      in the coming decade.

PMID- 15575625
TI  - Identification of sequence-specific DNA binding proteins.

PMID- 15575626
TI  - Expression of exogenous mRNAs to study gene function in the sea urchin embryo.
AB  - Expression of exogenous mRNAs has become part of the standard approach to
      studying gene function during development of the sea urchin. The method is simple
      and reliable, protocols for the preparation of synthetic mRNAs are well
      described, and the technique to transfer them into eggs is efficient. The protein
      encoded by these mRNAs can be designed to address a variety of biological
      questions and their DNA matrices are easily constructed by standard molecular
      biology techniques. The method aims to simulate gain or loss of gene function,
      and the phenotypes obtained are characterized using an increasing number of
      molecular markers. With the completion of the S. purpuratus genome project, the
      complete set of genes from the sea urchin will become available. Expression of
      mRNA will be an invaluable tool to study the function of newly identified genes
      and their protein products and to determine their positions within the networks
      of gene and protein interactions that control development.

PMID- 15575627
TI  - Disruption of gene function using antisense morpholinos.

PMID- 15575628
TI  - Generation and use of transgenic ascidian embryos.

PMID- 15575629
TI  - Genomic resources for the study of sea urchin development.

PMID- 15575630
TI  - Genomic resources for ascidians: sequence/expression databases and genome
      projects.

PMID- 15575631
TI  - Gene regulatory network analysis in sea urchin embryos.
AB  - It may safely be predicted that GRN analysis will become increasingly important.
      It will come to underlie the causal study of development, the major effort
      underway to understand the regulatory code built into animal genomes and also the
      evolution of these genomes. Partly by serendipity, sea urchin embryos turn out to
      be a superb experimental material for GRN analysis. Their natural properties
      have, in turn, influenced the predilections of those who work on them, and
      between them and us, so to speak, this is now a developmental system of which we
      are rapidly gaining an unusually complete understanding. The causal linkages that
      control development of the whole embryo will be revealed, leading all the way
      from the heritable genomic regulatory code to the events of embryology. The
      fundamental experimental operation is the perturbation analysis: Here is where
      causality permeates the exploration. We have in this chapter summarized in some
      detail the requirements for perturbation GRN analysis in sea urchin embryos. But
      that is not all, nor is it enough to enable the assembly of a GRN: What is
      required is the combined application of elegant computational methods, of gene
      regulation molecular biology, of genomic sequence data, and of experimental
      embryology. As the results crystallize together, we can begin to see how far this
      powerful combination of methods and ideas is going to carry us.

PMID- 15575632
TI  - Sea urchin gametes in the teaching laboratory: good experiments and good
      experiences.

PMID- 15575633
TI  - Realizing advanced nursing practice through reflection.

PMID- 15575634
TI  - Sepsis strategies: an ICU package?
AB  - --Mortality of patients with severe sepsis remains at unacceptable levels and
      recent new strategies are not being widely embraced. --Five strategies are
      discussed within this article [low tidal volumes in acute lung injury/acute
      respiratory distress syndrome, early goal-directed therapy, drotrecogin alfa
      (activated), moderate dose corticosteroids and tight control of blood glucose]. -
      The critical care nurse plays a leading role in the detection, monitoring and
      treatment of patients with severe sepsis. --The role of the critical care nurse
      within the multidisciplinary team is explored. --Education, combination of
      strategies and the use of protocols are discussed.

PMID- 15575635
TI  - An exploration of the ethical dimensions pertinent to gaining consent for
      thrombolysis.
AB  - --This paper explores some of the pertinent ethical principles involved in
      gaining consent in thrombolysis, relevant to both nurses and paramedics. --It
      describes ethical concerns regarding this practice. --Two key themes that have
      been explored are around the issue of autonomy and paternalism. --With nurse
      initiated thrombolysis gaining momentum, an awareness of key ethical dimensions
      is fundamental.

PMID- 15575636
TI  - Ms. B and legal competence: interprofessional collaboration and nurse autonomy.
AB  - --Ms. B's wish for withdrawal of treatment was refused. --The nurses' role and
      autonomy in the decision-making is unclear. --Historically, tensions have existed
      in the doctor-nurse relationship. --Interprofessional collaboration is encouraged
      in order to facilitate team working. --Evidence is lacking that this is working
      and suggests continuing problems. --Legal and ethical education needs emphasizing
      in order to ensure respect for patient autonomy.

PMID- 15575637
TI  - A review of the efficacy and safety of opioid analgesics post-craniotomy.
AB  - --Codeine phosphate is the most commonly used analgesic post-craniotomy. --It is
      argued, in this paper, that codeine phosphate is an unpredictable pro-drug that
      does not equate to a safe and effective method of providing analgesia post
      craniotomy. --Lack of evidence supporting tramadol's usage and concerns over its
      interactions and side effects mean its use cannot be advocated. --The traditional
      justification for withholding morphine in post-craniotomy pain appears to be
      largely based on anecdotal evidence. --Raising awareness among critical care
      nurses of the pharmacological properties of the analgesics used is imperative, if
      post-craniotomy pain is to be adequately treated. --There is an explicit
      challenge to the neurosurgical community to re-evaluate their pain-management
      strategies in the post-craniotomy patient.

PMID- 15575638
TI  - [Gudrun Gille has been associated with the German Journal for Nurses for 30
      years].

PMID- 15575639
TI  - [Pediatric nurses. An Indian knows no pain].

PMID- 15575640
TI  - [Child health promotion in pediatric nursing].

PMID- 15575641
TI  - [Pediatric nursing. Help--my parents are sick].

PMID- 15575642
TI  - [Colors, space and health].

PMID- 15575643
TI  - [The right to emotion in face of death].

PMID- 15575644
TI  - [Our health in 2020].

PMID- 15575645
TI  - [A theme for nursing management. Evacuation].

PMID- 15575646
TI  - [Achieving one's goal and nevertheless remaining a women: the funny principle].

PMID- 15575647
TI  - [Functional and intensive nursing remains in the background].

PMID- 15575648
TI  - [Performing nursing visits and self knowledge].

PMID- 15575650
TI  - Facile deprotection of O-Cbz-protected nucleosides by hydrogenolysis: an
      alternative to O-benzyl ether-protected nucleosides.
AB  - [reaction: see text] Because of side-reactions encountered during hydrogenolysis,
      benzyl ethers are usually not an effective protecting group for nucleosides.
      Benzyloxycarbamates provide an alternative to traditional benzyl ethers for
      protection of nucleoside hydroxyl groups, as they are much more labile to
      hydrogenolysis. Deprotection conditions using transfer hydrogenolysis are
      described that avoid the reduction of the pyrimidine nucleobase during deblocking
      of O-Cbz-protected nucleosides. Additionally, an experiment is described that
      suggests the nucleobase component of a nucleoside is responsible for the sluggish
      hydrogenolysis of nucleosides.

PMID- 15575651
TI  - A test for homology: photoactive crystalline assemblies involving linear
      templates based on a homologous series of phloroglucinols.
AB  - [reaction: see text] Cocrystallization of trans-1,2-bis(4-pyridyl)ethylene (4,4'
      bpe) with eight members of a homologous series of phloroglucinols 1a-h yields
      molecular solids 2(1a-h).2(4,4'-bpe) with components held together by four O
      H...N hydrogen bonds. In each case, the molecules assemble to form a discrete
      four-component assembly with olefins preorganized for a [2 + 2]
      photodimerization. UV irradiation of each member in the series of solids produces
      rctt-tetrakis(4-pyridyl)cyclobutane (4,4'-tpcb), stereospecifically, in up to
      100% yield.

PMID- 15575652
TI  - Construction of optically active CF3-containing quaternary carbon centers via
      stereospecific S(N)2' reaction.
AB  - [reaction: see text] Phosphates from 3-substituted 4,4,4-trifluorobut-2-en-1-ols
      were found to be effective for construction of CF3-containing quaternary carbon
      centers by way of Cu(I)-catalyzed Grignard reactions in the presence of catalytic
      amounts of CuCN and trimethylsilyl chloride (TMSCl) in an anti S(N)2' manner.

PMID- 15575653
TI  - A new imidazolium cavitand for the recognition of dicarboxylates.
AB  - [structure: see text] A new cavitand bearing four imidazolium groups was
      synthesized for the recognition of anions through (C-H)+...X- hydrogen bond
      formation. The binding properties toward various anions including dicarboxylates
      were examined on the basis of 1H NMR spectroscopic experiments.

PMID- 15575654
TI  - Rapid synthesis of acyl transfer auxiliaries for cysteine-free native
      glycopeptide ligation.
AB  - [reaction: see text] Rapid, facile routes to the TFA-cleavable 4,5,6-trimethoxy-2
      mercaptobenzyl and 1-(2,4-dimethoxyphenyl)-2-mercaptoethyl classes of auxiliaries
      for cysteine-free native chemical ligation are described. Rapid synthesis,
      coupled with mild cleavage conditions will undoubtedly broaden the utility of
      such auxiliaries, particularly where chemically fragile peptide modifications
      such as glycosylation are present.

PMID- 15575655
TI  - The use of squaric acid as a scaffold for cofacial phenyl rings.
AB  - [structure: see text] To examine the possibility of using squaric acid as a
      scaffold for organizing phenyl rings in a cofacial orientation, we undertook an
      investigation of the conformational preferences of secondary and tertiary N
      phenylsquaramides. In secondary squaramides, the extended ZZ conformation is
      preferred, while in the N-methyl derivative, the folded EE conformation with
      cofacial phenyl rings is preferred. This conformational switch is likely driven
      by a combination of steric and electronic factors.

PMID- 15575656
TI  - Novel pi-expanded radialene macrocycles with inner cavity.
AB  - [structure: see text] Polyenyne macrocycles with pi-extended [9]- and
      [12]radialene frameworks have been synthesized. These radialenes exhibit
      restricted rotation of the aromatic rings, and the D3- and D4-symmetric
      structures in solutions have been determined by dynamic NMR. The macrocyclic
      radialenes bear small to medium inner cavities, and the small cavity of the pi
      extended [9]radialene can incorporate a silver cation.

PMID- 15575657
TI  - Photochemical generation of nitrenium ions from protonated 1,1-diarylhydrazines.
AB  - [reaction: see text] Laser flash photolysis experiments, chemical trapping
      studies, and time-dependent density functional theory calculations demonstrate
      that photolysis of protonated 1,1-diarylhydrazines generates N,N-diarylnitrenium
      ions.

PMID- 15575658
TI  - Stereospecific deoxygenation of phosphine oxides with retention of configuration
      using triphenylphosphine or triethyl phosphite as an oxygen acceptor.
AB  - [reaction: see text] A new protocol for deoxygenation of various phosphine oxides
      with retention of configuration is described. The advantage of the new method
      includes milder conditions and considerably shortened reaction times. Mechanistic
      studies about the oxygen transfer between the starting phosphine oxide and the
      sacrificial triphenylphosphine are also presented.

PMID- 15575659
TI  - N-heterocyclic carbenes as highly efficient catalysts for the cyclotrimerization
      of isocyanates.
AB  - [reaction: see text] A series of N-heterocyclic carbenes (NHCs) were evaluated as
      potential catalysts for the cyclotrimerization of isocyanates to afford
      isocyanurates. 1,3-Bis-(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene
      (SIPr) was found to be a highly efficient catalyst for the cyclotrimerization of
      a variety of isocyanates.

PMID- 15575660
TI  - Tandem functionalization of nonactivated alkenes and alkynes in intramolecular N
      acyloxyiminium ion carbocyclization. Synthesis of 6-substituted hydroindole 2
      carboxylic acids.
AB  - [reaction: see text] Five-membered N-Boc acyliminium ions derived from L
      pyroglutamic acid harboring 4-butenyl and 4-butynyl tethers undergo Lewis acid
      mediated halo and tandem Friedel-Crafts carbocyclization within minutes at -78
      degrees C to give stereodefined 6-substituted octahydroindole and hexahydroindole
      2-carboxylic acid methyl esters, respectively. The cyclic vinyl bromides are
      excellent substrates for Pd-catalyzed Suzuki-Miyaura, Heck, and Stille couplings.
      The method also provides access to enantiopure sp2- and sp3-arylated azabicyclics
      that are novel and versatile scaffolds for chemical diversification.

PMID- 15575661
TI  - Ortho alkylation of aromatic ketimine with functionalized alkene by Rh(I)
      catalyst.
AB  - [reaction: see text] The reaction of the imine of aromatic ketones with
      functionalized alkenes was performed under a catalytic amount of (PPh3)3RhCl, and
      corresponding ortho-alkylated ketones were obtained after hydrolysis. A variety
      of functional groups in the alkene were tolerated in this ortho alkylation. This
      procedure expands the scope of ortho alkylation to the direct ortho
      functionalization of aromatic ketones.

PMID- 15575662
TI  - An efficient total synthesis of (+/-)-lycoramine.
AB  - [reaction: see text] A short and unique approach to (+/-)-lycoramine as one of
      the galanthamine-type alkaloids has been efficiently developed. The alternative
      advantage lies in that three stereocenters, including a crucial quaternary carbon
      center, were constructed with high diasteroselectivity via a key one-step NBS
      mediated semipinacol rearrangement of the allylic alcohol.

PMID- 15575663
TI  - Asymmetric transfer hydrogenation of aryl ketones catalyzed by salt-free two
      samarium centers supported by a chiral multidentate alkoxy ligand.
AB  - [reaction: see text] We synthesized a chiral multidentate ligand, (R,R,R,R)
      N,N,N',N'-tetra(2-hydroxy-2-phenylethyl)-1,3-xylylene diamine [(R)-2], which can
      support two metals at adjacent positions. Asymmetric transfer hydrogenation of
      acetophenone and its derivatives was conducted by using salt-free bimetallic
      lanthanoid complexes of (R)-2, and the combination of two samarium atoms and (R)
      2 was found to be the best catalyst system for asymmetric transfer hydrogenation
      of aryl ketones in high enantioselectivity (up to >99% ee).

PMID- 15575664
TI  - Peptide nucleic acids with a flexible secondary amine in the backbone maintain
      oligonucleotide binding affinity.
AB  - [structure: see text] Replacing a secondary amide in a peptide nucleic acid
      backbone with a more flexible secondary amine affords an oligomer that
      surprisingly maintains the same binding affinity to complementary
      oligonucleotides as the unmodified polyamide oligomer.

PMID- 15575665
TI  - Synthesis and properties of hyperbranched conjugated porphyrins.
AB  - [reaction: see text] Hyperbranched conjugated porphyrin arrays were prepared by
      one-pot Suzuki polycondensation of AB3 and AB3 + C4 approaches.

PMID- 15575666
TI  - Total synthesis of anachelin H.
AB  - [structure: see text] The first total synthesis of anachelin H is reported.
      Starting from L-Ser, a stereodivergent synthesis of the polyketide fragment
      resulting in all possible diastereoisomers is described. The alkaloid peptide
      fragment is prepared via a tellurium-mediated oxidative aza annulation as the key
      step. Coupling of the fragments gave synthetic anachelin H, which was found to be
      identical to a sample of the natural product, thus confirming the configuration
      by total synthesis.

PMID- 15575667
TI  - Parallel supported synthesis of polyamine-imidazole conjugates.
AB  - [reaction: see text] A small collection of nine polyamine-imidazole conjugates,
      potentially acting as RNases A mimics, has been synthesized on SynPhase lanterns
      using amino alcohols and diamines as building blocks. Couplings were performed
      via S(N)2 alkylation of methanesulfonates with amines. The final introduction of
      N-4-nitrobenzyloxycarbonyldiamines allowed easy purification of the cleaved
      compounds.

PMID- 15575668
TI  - Application of chiral lanthanide shift reagents for assignment of absolute
      configuration of alcohols.
AB  - [structure: see text] The absolute configuration of secondary and tertiary
      alcohols can be predicted from analysis of the chemical shift behaviors of the CX
      and CY-carbons in the presence of (R)- and (S)-Pr(tfc)3 as formulated in the
      boxes.

PMID- 15575669
TI  - Use of a chiral praseodymium shift reagent in predicting the complete
      stereostructure of glisoprenin A.
AB  - [structure: see text] The complete stereostructure of glisoprenin A has been
      predicted via analysis of the 13C NMR behaviors in the presence of (R)- and (S)
      Pr(tfc)3.

PMID- 15575670
TI  - Validation of lanthanide chiral shift reagents for determination of absolute
      configuration: total synthesis of glisoprenin A.
AB  - [structure: see text] The complete stereostructure of the natural product (+)
      glisoprenin A had been predicted via a novel application of chiral lanthanide
      shift reagents. Confirmation of the predicted stereostructure of (+)-glisoprenin
      A and validation of the chiral lanthanide shift approach have now been achieved
      through total synthesis.

PMID- 15575671
TI  - Cyclic sulfamidates as vehicles for the synthesis of substituted lactams.
AB  - [reaction: see text] A structurally diverse series of mono- and disubstituted 1,2
      and 1,3-cyclic sulfamidates react with stabilized enolates, including malonate
      and phosphonoacetate variants, to provide, after lactamization, substituted and
      alpha-functionalized pyrrolidinone and piperidinone derivatives.

PMID- 15575672
TI  - Highly efficient two-step synthesis of C-sp3-centered geminal diiodides.
AB  - [reaction: see text] Trisubstituted gem-diiodoalkenes of functionalized chains
      are efficiently reduced to the corresponding terminal geminal diiodides in high
      yields upon treatment with the diazene precursor, diethyl 4-(hydrazinosulfonyl)
      benzyl phosphonate.

PMID- 15575673
TI  - Expanding the Hoogsteen edge of 2'-deoxyguanosine: consequences for G-quadruplex
      formation.
AB  - [structure: see text] The synthesis and self-assembling properties of 8-aryl-2'
      deoxyguanosine derivatives are described. Our studies suggest that a properly
      placed acetyl group can increase the stability and specificity of the resulting G
      quadruplex supramolecules by enhancing noncovalent interactions such as hydrogen
      bonds and pi-stacking.

PMID- 15575674
TI  - Using nucleophilic substitution reactions to understand how a remote alkyl or
      alkoxy substituent influences the conformation of eight-membered ring
      oxocarbenium ions.
AB  - [reaction: see text] A remote alkoxy substituent strongly stabilizes one
      particular conformer of an eight-membered ring oxocarbenium ion by a through
      space electrostatic effect. X-ray crystallographic analysis of a crystalline
      derivative proves that kinetically controlled nucleophilic substitution favors
      the 1,4-trans product. Nucleophilic substitution of the corresponding alkyl
      substituted acetate, however, is unselective. A computational model has been
      developed and experimentally validated to predict the low-energy conformers of C3
      , C4-, or C5-alkyl- or alkoxy-substituted eight-membered ring oxocarbenium ions.

PMID- 15575675
TI  - Lewis acid-promoted annulation of O-quinonediimines by allylstannane: a facile
      synthesis of quinoxaline derivatives.
AB  - [reaction: see text] Lewis acid-promoted addition of allyltri-n-butylstannane to
      o-quinonediimines afforded tetrahydroquinoxaline derivatives or allylated amides
      depending on the nature of the substituent on imine nitrogen.

PMID- 15575676
TI  - Highly diastereoselective and enantioselective synthesis of enantiopure C2
      Symmetrical vicinal diamines by reductive homocoupling of chiral N-tert
      butanesulfinyl imines.
AB  - [reaction: see text] An efficient and straightforward method for the preparation
      of highly enantiomerically enriched C2-symmetrical vicinal diamines by the
      reductive homocoupling of aromatic N-tert-butanesulfinyl imines in the presence
      of SmI2 and HMPA was developed. It gives access to a variety of enantiopure C2
      symmetrical 1,2-diamines in a very mild and practical way.

PMID- 15575677
TI  - A chiral electrophilic selenium reagent to promote the kinetic resolution of
      racemic allylic alcohols.
AB  - [reaction: see text] The first example of a kinetic resolution process promoted
      by electrophilic selenium reagents is reported. Racemic allylic alcohols react
      with half equivalents of a selenenylating agent in methanol leading to the
      regiospecific formation of the corresponding addition products with a very high
      level of facial selectivity (from 95:5 to 98:2 dr). The unreacted alcohols can be
      recovered in an optically enriched form (from 90 to 94% ee).

PMID- 15575678
TI  - Palladium-catalyzed intramolecular O-arylation of enolates: application to
      benzo[b]furan synthesis.
AB  - [reaction: see text] A catalyst generated from Pd2(dba)3 and the ligand DPEphos
      effects intramolecular C-O bond formation between enolates and aryl halides in
      the conversion of 1-(2-haloaryl)ketones directly into the corresponding
      benzofurans. Both cyclic and acyclic ketones are efficient substrates. Thio
      ketones can also be employed allowing the preparation of the corresponding
      benzothiophenes.

PMID- 15575679
TI  - Synthesis of 6-phenanthridinones and their heterocyclic analogues through
      palladium-catalyzed sequential aryl-aryl and N-aryl coupling.
AB  - [reaction: see text] 6-Phenanthridinones and their heterocyclic analogues were
      synthesized through a one-pot procedure based on consecutive Pd-catalyzed aryl
      aryl and N-aryl coupling from iodoarenes ortho-substituted by electron-releasing
      substituents and amides of o-bromoarene- and heteroarenecarboxylic acids.

PMID- 15575680
TI  - Novel intramolecular rearrangement leading to the synthesis of biheterocyclic
      indole-benzoimidazole derivatives on solid phase.
AB  - [reaction: see text] A novel intramolecular SNAr rearrangement observed during
      the S-alkylation of benzoimidazole-2-thione with alpha-haloacetophenone is
      reported. The rearrangement led to the formation of a new benzoimidazole-based
      intermediate, which is further utilized for the generation of a new
      biheterocyclic indole-benzimidazole derivatives with a two-point diversity.

PMID- 15575681
TI  - Synthesis and properties of gem-(difluorocyclopropyl)amine derivatives of
      bicyclo[n.1.0]alkanes.
AB  - [reaction: see text] Generation of difluorocarbene(carbenoid) in the presence of
      enamines derived from cyclic ketones results in overall insertion of CF2 to
      produce bicyclic difluorocyclopropylamines. These adducts are very weakly basic,
      and their thermal stabilities vary markedly with their structures.

PMID- 15575682
TI  - Ammonium chloride promoted Ugi four-component, five-center reaction of alpha
      substituted alpha-isocyano acetic acid: a strong solvent effect.
AB  - [reaction: see text] Conditions have been developed for the multicomponent
      synthesis of di- and tetrapeptide (7) based on the unique reactivity of alpha
      isocyano acetic acid (4 and its alpha-substituted derivatives) by an Ugi four
      component, five-center reaction. Simply mixing 4, a carbonyl compound (aldehyde
      or ketone, 8), and a secondary amine (9) (ratio: 1:1:2) in toluene in the
      presence of 1.5 equiv of ammonium chloride afforded the desired product in good
      to excellent yield as a mixture of two diastereomers.

PMID- 15575683
TI  - Efficient synthesis of 4-aminoquinazoline and thieno[3,2-d]pyrimidin-4-ylamine
      derivatives by microwave irradiation.
AB  - [reaction: see text] A simple, efficient, and high-yielding synthesis of
      quinazolin-4-ylamine and thieno[3,2-d]pyrimidin-4-ylamine derivatives is reported
      under microwave irradiation conditions. Reaction conditions including
      temperature, solvent, and reaction time have been studied. An efficient parallel
      workup procedure was developed to generate a small library (23 compounds) in a
      short time period.

PMID- 15575684
TI  - Synthesis of a tripeptide derivative containing the gln-arg hydroxyethylene
      dipeptide isostere.
AB  - [structure: see text] The protected hydroxyethylene dipeptide isostere of Gln-Arg
      and the tripeptide derivative 1 were synthesized as components of potential
      peptidase inhibitors.

PMID- 15575685
TI  - Synthesis of a Gln-Phe hydroxy-ethylene dipeptide isostere.
AB  - [structure: see text] The protected Gln-Phe hydroxyethylene dipeptide isostere 1
      was synthesized as a precursor for preparation of potential inhibitors of
      Botulinum neurotoxin B metalloprotease. The method allows for the synthesis of
      additional hydroxyethylene dipeptide isosteres such as 2 with functionalized P1
      side chains. The isosteres prepared were coupled with a dipeptide to produce
      protected pseudotetrapeptide derivatives.

PMID- 15575686
TI  - Gamma-lactone-tethered ring-closing metathesis. A route to enantiomerically
      enriched gamma-lactones alpha,beta-fused to medium-sized rings.
AB  - [reaction: see text] The stereoselective alkylation of alpha-(phenylsulfonyl)
      beta-[(methoxycarbonyl)methyl]-gamma-lactones obtained by the base-induced
      cyclization of enantiomerically enriched alpha-[(phenylthio)acyl]-alpha,beta
      unsaturated esters and ring-closing olefin metathesis (RCM) are the basis of a
      new approach for gaining access to gamma-lactones that are alpha,beta-fused to
      medium-sized carbocycles and cyclic ethers.

PMID- 15575687
TI  - Oxygenation of benzyldimethylamine by singlet oxygen. Products and mechanism.
AB  - [reaction: see text] A product study of the reaction of benzyldimethylamine (1)
      with thermally and photochemically generated 1O2 in MeCN was carried out.
      Benzaldehyde and N-benzyl-N-methylformamide are the reaction products,
      oxygenation representing ca. 9% of the overall quenching of 1O2 by 1. The
      temperature effect and the intermolecular and intramolecular kinetic deuterium
      isotope effects were also determined. It is suggested that the products derive
      from an intracomplex hydrogen atom transfer in a reversibly formed charge
      transfer complex.

PMID- 15575688
TI  - Manipulation of N,O-nucleophilicity: efficient formation of 4-N-substituted 2,4
      dihydro-3H-1,2,4-triazolin-3-ones.
AB  - A new efficient two-step synthesis of 2,4-dihydro-3H-1,2,4-triazolin-3-ones
      (triazolinones) from readily available amines is reported. Our novel conditions
      using hexamethyl disilazane, bromotrimethylsilane, and a catalytic amount of
      ammonium sulfate smoothly cyclize 1-formyl and 1-acetyl semicarbazides to the
      target triazolinones. This transformation features simultaneous manipulation of N
      and O-nucleophilicity as well as differentiation of the nucleophilicity of a
      urea and an acyl carbonyl.

PMID- 15575691
TI  - Microbial surfaces investigated using atomic force microscopy.
AB  - This paper is dedicated to atomic force microscopy (AFM) as a progressive tool
      for imaging bacterial surfaces and probing their properties. The description of
      the technique is complemented by the explanation of the method's artifacts
      typical, in particular, for the imaging of bacterial cells. Sample preparation
      techniques are summarized in a separate section. Special attention is paid to the
      differences in imaging of gram-positive and gram-negative bacteria. Probing of
      mechanical properties, including elastic modulus, fragility, and adhesion of the
      cell walls is emphasized. The advantages of AFM in the studies of real-time
      cellular dynamical processes are illustrated by the experiment with the
      germination of spores.

PMID- 15575692
TI  - Stimulation, monitoring, and analysis of pathway dynamics by metabolic profiling
      in the aromatic amino acid pathway.
AB  - Using a concerted approach of biochemical standard preparation, analytical access
      via LC-MS/MS, glucose pulse, metabolic profiling, and statistical data analysis,
      the metabolism dynamics in the aromatic amino acid pathway has been stimulated,
      monitored, and analyzed in different tyrosine-auxotrophic L-phenylalanine
      producing Escherichia coli strains. During the observation window from -4 s
      (before) up to 27 s after the glucose pulse, the dynamics of the first five
      enzymatic reactions in the aromatic amino acid pathway was observed by measuring
      intracellular concentrations of 3-deoxy-d-arabino-heptulosonate 7-phosphate
      DAH(P), 3-dehydroquinate (3-DHQ), 3-dehydroshikimate (3-DHS), shikimate 3
      phosphate (S3P), and shikimate (SHI), together with the pathway precursors
      phosphoenolpyruvate (PEP) and P5P, the lumped pentose phosphate pool as an
      alternative to the nondetectable erythrose 4-phosphate (E4P). Provided that a
      sufficient fortification of the carbon flux into the pathway of interest is
      ensured, respective metabolism dynamics can be observed. On the basis of the
      intracellular pool measurements, the standardized pool velocities were
      calculated, and a simple, data-driven criterion--called "pool efflux capacity"
      (PEC)--is derived. Despite its simplifying system description, the criterion
      managed to identify the well-known AroB limitation in the E. coli strain A
      (genotype delta(pheA tyrA aroF)/pJF119EH aroF(fbr) pheA(fbr) amp) and it also
      succeeded to identify AroL and AroA (in strain B, genotype delta(pheA tyrA
      aroF)/pJF119EH aroF(fbr) pheA(fbr) aroB amp) as promising metabolic engineering
      targets to alleviate respective flux control in subsequent L-Phe producing
      strains. Furthermore, using of a simple correlation analysis, the reconstruction
      of the metabolite sequence of the observed pathway was enabled. The results
      underline the necessity to extend the focus of glucose pulse experiments by
      studying not only the central metabolism but also anabolic pathways.

PMID- 15575693
TI  - A high-throughput approach to promoter study using green fluorescent protein.
AB  - Green fluorescent protein (GFP) is a reporter that has had a significant impact
      due to its many advantages over other reporter genes: it is autofluorescent, it
      enables in situ detection, it is relatively small, and it is also nontoxic. By
      cloning a gene promoter upstream of the gfp gene and exposing the living cells
      transformed with the fusion to the specific inducer or repressor, gene expression
      can be real-time monitored by continuous quantitative measurement of the green
      fluorescence emitted by GFP. In this work, a promoter study using promoter-gfp
      fusions was conducted in 96-well plates. Because they were placed in an automated
      incubating and shaking microplate reader, the wells functioned as microscale
      bioreactors, allowing for parallel experiments and data analysis. In the study
      described here, an overexpression promoter (pBAD promoter) and two comparatively
      weak promoters (sodA and acnA in Escherichia coli SoxRS regulon) were studied in
      both endpoint and kinetics formats. Our results with the pBAD promoter revealed
      insight on its regulation, which is tightly controlled by levels of arabinose and
      glucose. Results on weak oxidative stress promoters (for sodA and acnA genes)
      were striking in that significant induction was observed when they were under a
      superoxide stress in plates. They both displayed dose-dependent induction to
      paraquat-generated superoxide anion, with sodA leading acnA in strength and time.
      These results, spanning highly inducible promoters for protein overexpression and
      weakly inducible promoters of metabolic interest, demonstrate that the approach
      is relatively easily executed and can be used for quantitative and temporal
      promoter studies in a high throughput format.

PMID- 15575694
TI  - Xylose metabolism in Debaryomyces hansenii UFV-170. Effect of the specific oxygen
      uptake rate.
AB  - The new yeast Debaryomyces hansenii UFV-170 was tested in this work in batch
      experiments under variable oxygenation conditions. To get additional information
      on its fermentative metabolism, a stoichiometric network was proposed and checked
      through a bioenergetic study performed using the experimental data of product and
      substrate concentrations. The yeast metabolism resulted to be practically
      inactive under strict oxygen-limited conditions (qO2 = 12.0 mmol(O2) C-mol(DM)(
      1) h(-1)), as expected by the impossibility of regenerating NADH2+. Significant
      fractions of the carbon source were addressed to both respiration and biomass
      growth under excess oxygen levels (qO2 > or = 55.0 mmol(O2) C-mol(DM)(-1) h(-1)),
      thus affecting xylitol yield (Y(P/S) = 0.41-0.52 g g(-1)). Semi-aerobic
      conditions (qO2 = 26.8 mmol(O2) C-mol(DM)(-1) h(-1)) were able to ensure the best
      xylitol production performance (Pmax = 76.6 g L(-1)), minimizing the fractions of
      the carbon source addressed either to respiration or biomass production and
      increasing Y(P/S) up to 0.73 g g(-1). An average P/O ratio of about 1.0 mol(ATP)
      mol(O)(-1) allowed estimation of the main kinetic-bioenergetic parameters of the
      biosystem. The overall ATP requirements of biomass were found to be particularly
      high and dependent on the oxygen availability in the medium as well as on the
      physiological state of the culture. Under semi-aerobic and aerobic conditions,
      they varied in the ranges 13.5-15.4 and 9.74-10.2 mol(ATP) C-mol(DM)(-1),
      respectively, whereas during the best semi-aerobic bioconversion they
      progressively increased from 5.68 to 24.7 mol(ATP) C-mol(DM)(-1). After a
      starting phase of adaptation to the medium, the cell achieved a phase of
      decelerated growth during which its excellent xylose-to-xylitol capacity kept
      almost constant after 112 h up to the end of the run.

PMID- 15575695
TI  - Production of biologically active Bacillus anthracis edema factor in Escherichia
      coli.
AB  - Anthrax is caused by the gram-positive spore-forming bacterium Bacillus
      anthracis. The anthrax toxin consists of three proteins, protective antigen (PA),
      lethal factor (LF), and edema factor (EF). PA facilitates the translocation of LF
      and EF into the cytosol of mammalian cells. LF is thought to be a zinc-dependent
      metalloprotease that results in death. EF is a calmodulin- and calcium-dependent
      adenylate cyclase that causes edema upon entrance into the cytosol by elevating
      the cAMP levels in cells. Previous efforts to produce recombinant EF (rEF) in
      Escherichia coli yielded only 2.5 mg of rEF per liter of culture. In this work,
      we produced soluble rEF in large quantities in both the periplasm and cytoplasm
      of E. coli from shake flasks and fermentors. The rEF protein was purified by
      standard chromatography and yielded >97% pure, biologically active rEF. Yields of
      purified rEF from medium cell density fermentations resulted in up to 2.38 g/L of
      highly pure, biologically active rEF protein. These results exhibit the ability
      to generate gram quantities of active rEF from E. coli.

PMID- 15575696
TI  - Improved bioconversion of 15-fluoro-6-deoxyerythronolide B to 15-fluoro
      erythromycin A by overexpression of the eryK Gene in Saccharopolyspora erythraea.
AB  - The bioconversion of a 6-deoxyerythronolide B analogue to the corresponding
      erythromycin A analogue (R-EryA) by a Saccharopolyspora erythraea mutant lacking
      the ketosynthase in the first polyketide synthase module was significantly
      improved by changing fluxes at a key branch point affecting the erythromycin
      congener distribution. This was achieved by integrating an additional copy of the
      eryK gene into the chromosome under control of the eryAIp promoter. Real-time PCR
      analysis of RNA confirmed higher expression of eryK in the resulting strain, S.
      erythraea K301-105B, compared to its parent. In shake flasks, K301-105B produced
      less of the shunt product 15-fluoro-erythromycin B (15F-EryB), suggesting a shift
      in congener distribution toward the desired product, 15-fluoro-erythromycin A
      (15F-EryA). In bioreactor studies, K301-105B produced 1.3 g/L of 15F-EryA with 75
      80% molar yield on fed precursor, compared with 0.9 g/L 15F-EryA with 50-55%
      molar yield on fed precursor by the parent strain. At higher precursor feed
      rates, K301-105B produced 3.5 g/L of 15F-EryA while maintaining 75-80% molar
      yield on fed precursor.

PMID- 15575697
TI  - Effect of subculture and elicitation on instability of taxol production in Taxus
      sp. suspension cultures.
AB  - The production of secondary metabolites through plant cell suspension cultures is
      challenging because the level and pattern of production is often unstable and
      unpredictable. To investigate the factors affecting instability of secondary
      metabolite production, high Taxol (paclitaxel)-producing Taxus cultures induced
      by methyl jasmonate elicitation and their low Taxol-producing counterparts were
      compared with respect to growth and Taxol production kinetics. With Taxus
      subcultures we observe alternating states of high and low productivity. Parental
      cultures and their subcultures from five different cell lines were used to test
      whether a high-producing culture grows more slowly or dies more rapidly than a
      low-producing one. These cell lines were of three types: (1) Taxol-producing with
      and without methyl jasmonate, (2) Taxol-producing only upon elicitation, and (3)
      nonproducing. High-producing cultures show growth inhibition upon subculture,
      whereas nonproducing elicited cultures show little growth inhibition. Thus,
      growth inhibition is primarily due to Taxol or taxane accumulation and not a
      direct result of methyl jasmonate treatment. Through media exchange between high-
      and low-producing cultures, it appears that culture components generated by cells
      alter culture properties. To assess variability as a function of culture lineage,
      two groups of replicate cultures were generated either with a mixing of the
      parental flasks or segregation of parental flasks at each subculture. Although
      parental culture mixing did not reduce flask-to-flask variation, the production
      level of Taxol in subcultures resulting from mixing inocula was sustained at a
      higher level relative to segregated subcultures. The results are consistent with
      the possibility of cell signaling within the population that can induce Taxol
      production.

PMID- 15575698
TI  - Establishment of N-acetylmannosamine (ManNAc) analogue-resistant cell lines as
      improved hosts for sialic acid engineering applications.
AB  - Metabolic substrate-based sialic acid engineering techniques, where exogenously
      supplied N-acetylmannosamine (ManNAc) analogues are utilized by the sialic acid
      biosynthetic pathway, allow the cell surface to be endowed with novel physical
      and chemical properties and show promise for increasing the quality of
      recombinant glycoproteins. The in vitro toxicity of many ManNAc analogues,
      however, hinders the large-scale adoption of this technology. In this study, we
      used a selection strategy where cells were subjected to progressively higher
      levels of ManNAc analogues to establish novel cell lines that showed decreased
      sensitivity to analogue-induced in vitro toxicity. The decreased sensitivity to
      sugar analogue-induced apoptosis, demonstrated by the Annexin V-FITC detection
      method and DNA fragmentation assays, corresponded to increased sialic acid
      production in the resistant cell lines. The ManNAc analogue-resistant cell lines
      exhibited cross-resistance to apoptosis induced by staurosporine and an apoptosis
      activating Fas antibody. We propose that the selection strategy employed to
      develop these novel cell lines, which serve as superior hosts for substrate-based
      sialic acid engineering applications, will generally apply to the development of
      host cell lines for biotechnology applications.

PMID- 15575699
TI  - Enhancing effect of low culture temperature on specific antibody productivity of
      recombinant Chinese hamster ovary cells: clonal variation.
AB  - To understand the different responses of recombinant Chinese hamster ovary (rCHO)
      cells to low culture temperature regarding specific productivity (q), 12 parental
      clones and their corresponding amplified clones producing a humanized antibody
      were cultivated at 32 and 37 degrees C. The specific growth rate of all clones,
      including both parental and amplified clones, decreased by 30-63% at 32 degrees
      C, compared to rates at 37 degrees C. In contrast, their specific antibody
      productivity (qAb) was significantly enhanced at 32 degrees C. Furthermore, the
      degree of qAb enhancement at 32 degrees C varied a lot from 4- to 25-fold among
      the parental clones. At 32 degrees C, most of the amplified clones, regardless of
      methotrexate (MTX) levels, also showed enhanced qAb but to a lesser extent than
      their parental clones. However, clone 14 amplified at 0.32 microM MTX (clone 14
      0.32) and clone 20 amplified at 1 microM MTX (clone 20-1.00), unlike their
      parental clones, did not show enhanced qAb at 32 degrees C. Thus, it was found
      that the enhancing effect of low culture temperature on q of rCHO cells depends
      on clones. Taken together, the results obtained here emphasize the importance of
      clonal selection for the successful application of low culture temperature to the
      enhanced foreign protein production in rCHO cells.

PMID- 15575700
TI  - Expression of active murine granulocyte-macrophage colony-stimulating factor in
      an Escherichia coli cell-free system.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important
      cytokine in the mammalian immune system. It has been expressed in Escherichia
      coli with the same biological activity as the native protein. Here, we report the
      synthesis of a murine recombinant GM-CSF in an E. coli cell-free protein
      synthesis system with a high yield. Since there are two disulfide bonds in the
      native structure of GM-CSF, an oxidizing redox potential of the reaction mixture
      was required. By pretreating the cell extract with iodoacetamide (IAM), the
      reducing activity of the cell extract was inactivated, and upon further
      application of an oxidized glutathione buffer, most of the synthesized GM-CSF was
      found in its oxidized form. However, the GM-CSF thus formed showed low activity
      because of poor folding. With the addition of DsbC, the periplasmic disulfide
      isomerase from E. coli, a high yield of active GM-CSF was produced in the cell
      free reaction. Finally, successful folding of the cell-free synthesized GM-CSF
      his6 was confirmed by its cell-proliferation activity after purification with a
      Ni2+ chelating column.

PMID- 15575701
TI  - Production and characterization of poly-beta-hydroxyalkanoate copolymers from
      Burkholderia cepacia utilizing xylose and levulinic acid.
AB  - Poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (P(3HB-co-3HV)) copolymers
      were prepared via shake-flask fermentations of Burkholderia cepacia (formerly
      Pseudomonas cepacia) containing 2.2% (w/v) xylose and concentrations of levulinic
      acid ranging from 0.07% to 0.67% (w/v). Periodic harvest of shake-flask cultures
      from 48 to 92 h post-inoculation yielded 4.4-5.3 g/L of dry cell biomass,
      containing 42-56% (w/w) P(3HB-co-3HV), with optimal product yield occurring
      between 66 and 74 h. Growth and PHA accumulation enhancement were observed with
      concentrations of levulinic acid from 0.07 to 0.52% (w/v), producing dry cell
      biomass and P(3HB-co-3HV) yields of 9.5 and 4.2 g/L, respectively, at the 0.52%
      (w/v) concentration of levulinic acid. Representative samples were subjected to
      compositional analysis by 300 MHz 1H and 150 MHz 13C NMR, indicating that these
      random copolymers contained between 0.8 and 61 mol % 3-hydroxyvalerate (3HV).
      Solvent-cast film samples were characterized by differential scanning
      calorimetry, which demonstrated melting temperatures (Tm) to decrease in a
      pseudoeutectic fashion from 174.3 degrees C (0.8 mol % 3HV) to a minimum of 154.2
      degrees C (25 mol % 3HV) and the glass transition temperatures (Tg) to decrease
      linearly from 2.1 to -11.9 degrees C as a function of increasing mol % 3HV.
      Thermogravimetric analysis of the copolymer series showed the temperature for
      onset of thermal decomposition (T(decomp)) to vary as a function of mol % 3HV
      from 273.4 to 225.5 degrees C. Intrinsic viscosities (eta) varied from 3.2 to 5.4
      dL/g, as determined by dilute solution viscometry. Viscosity average molecular
      weights (Mv) of the copolymers were determined to range from 469 to 919 kDa,
      indicating that these P(3HB-co-3HV) copolymers are of sufficient molecular mass
      for commercial application.

PMID- 15575702
TI  - Simultaneous in vitro protein synthesis using solid-phase DNA template.
AB  - In vitro protein synthesis is rapidly becoming an accepted tool in functional
      genomic analysis. We have demonstrated the in vitro synthesis of firefly
      luciferase on solid-phase template DNA, bound to wells in 96-well plates, using
      simultaneous transcription and translation in a wheat-germ extract system. The
      bound DNA template was stable and did not release during transcription. Coupled
      translation resulted in ca. 1.2 ng/microL luciferase synthesized, which is ca.
      one-fifth of that synthesized using conventional solution-phase coupled
      transcription and translation. Reuse of the DNA template was influenced by the
      complexity of the wheat-germ extract, which resulted in fouling of the
      transcription surface and reduction of protein synthesis after extended use. The
      approach developed in this study may enable the development of high-throughput,
      microscale protein synthesis platforms for use in functional genomic analysis.

PMID- 15575703
TI  - Experimental study of a ceramic microsparging aeration system in a pilot-scale
      animal cell culture.
AB  - The oxygen supply of cell cultures with the aid of free gas bubbles is an
      efficient process strategy in pharmaceutical production. If the cell-damaging
      impact of gas bubbles is reduced, direct aeration becomes a practical solution
      with scale-up potential and comparatively high oxygen transfer rates. In this
      paper a microsparging aeration system made of porous ceramic was compared with
      bubble-free membrane aeration. The sparging system was used for the long-term
      cultivation of mammalian cells in 2- to 100-L scale bioreactors and produced
      bubble sizes of 100-500 microm in diameter. Using a scale of 2.5 and 30 L, a cell
      density of 2.6 x 10(6) cells/mL was attained. When a 100-L scale was used, a
      density of 1.1 x 10(6) cells/mL was achieved, whereas a comparable membrane
      aerated system showed a cell density of 2.2 x 10(6) cells/mL. At relatively low
      agitation rates of less than 70 rpm in the sparged bioreactors, a homogeneous and
      constant oxygen concentration was kept in the medium. As a result of the
      different foam-forming tendency caused by the lower gas flow of the ceramic
      sparger compared to that of the standard aeration systems, we were able to
      develop an appropriate process control strategy. Furthermore, oxygen transfer
      measurements for the common stainless steel sparger and the ceramic sparger
      showed a 3-fold higher oxygen transfer coefficient for the ceramic sparger.

PMID- 15575704
TI  - A novel parallel shaken bioreactor system for continuous operation.
AB  - A novel continuous bioreactor system was developed as a shaken culture vessel for
      the investigation of the growth kinetics and product formation of microorganisms
      in milliscale. The novel bioreactor system mainly consists of a specially
      designed 250-mL shake flask with two inlets, one for gas supply and one for
      medium supply, and one combined outlet on the side of flask for exhaust gas and
      culture liquid. As a result of the circulating motion of the fermentation broth
      in the shake flask, the maximum liquid height reaches the edge of the outlet and
      the fermentation broth is accelerated into the outlet by centrifugal force.
      Additionally, the excess fermentation broth leaving the culture vessel is
      continuously driven by the exhaust gas. Because of the small scale and the simple
      handling it is possible to operate many of these shaken bioreactor vessels
      simultaneously. By using parallel vessels operated at different dilution rates on
      the same shaker, the data for a complete biomass over dilution rate (X-D) diagram
      of a biological culture can be evaluated in an efficient manner, thus saving
      money, materials, and time. Continuous fermentations of the yeast Saccharomyces
      cerevisiae H1022 (ATCC 32167) in the shaken bioreactor system and in a
      conventional stirred tank fermentor showed very similar results.

PMID- 15575705
TI  - Polymer development for enhanced delivery of phenol in a solid-liquid two-phase
      partitioning bioreactor.
AB  - Two-Phase Partitioning Bioreactors (TPPBs) have traditionally been used to
      partition toxic concentrations of xenobiotics from a cell-containing aqueous
      phase by means of an immiscible organic solvent and to deliver these substrates
      back to the cells on the basis of metabolic demand and the maintenance of
      thermodynamic equilibrium between the phases. A limitation of TPPBs, which use
      organic liquid solvents, is the possibility that the solvent can be bioavailable,
      and this has therefore limited organic liquid TPPBs to the use of pure strains of
      microbes. Solid polymer beads have recently been introduced as a replacement for
      liquid organic solvents, offering similar absorption properties but with the
      capability to be used with mixed microbial populations. The present work was
      aimed at identifying a polymer with a greater capacity for and more rapid uptake
      and release of phenol for use as the second phase in a mixed culture TPPB.
      Polarity and hydrogen bonding capabilities between polymer and phenol were
      considered in the screening and selection process of candidate polymers. Hytrel
      (a copolymer of poly(butylene terephthalate) and butylene ether glycol
      terephthalate) polymer beads, offered improved capacity (19 mg phenol/g polymer
      at a fixed initial phenol concentration of 2000 mg/L) and a greater diffusivity
      (1.54 x 10(-7) cm2/s) when compared to the capacity and diffusivity of previously
      used EVA (ethylene vinyl acetate) beads (12.4 mg phenol/g polymer and 3.73 x 10(
      9) cm2/s, respectively). Hytrel polymer beads were then used in a TPPB for the
      investigation of various substrate feeding strategies (fed-batch, bead
      replacement, and concentrated spikes of phenol), with rapid and complete phenol
      degradation shown in all cases.

PMID- 15575706
TI  - Growth model and metabolic activity of brewing yeast biofilm on the surface of
      spent grains: a biocatalyst for continuous beer fermentation.
AB  - In the continuous systems, such as continuous beer fermentation, immobilized
      cells are kept inside the bioreactor for long periods of time. Thus an important
      factor in the design and performance of the immobilized yeast reactor is
      immobilized cell viability and physiology. Both the decreasing specific glucose
      consumption rate (q(im)) and intracellular redox potential of the cells
      immobilized to spent grains during continuous cultivation in bubble-column
      reactor implied alterations in cell physiology. It was hypothesized that the
      changes of the physiological state of the immobilized brewing yeast were due to
      the aging process to which the immobilized yeast are exposed in the continuous
      reactor. The amount of an actively growing fraction (X(im)act) of the total
      immobilized biomass (X(im)) was subsequently estimated at approximately X(im)act
      = 0.12 g(IB) g(C)(-1) (IB = dry immobilized biomass, C = dry carrier). A
      mathematical model of the immobilized yeast biofilm growth on the surface of
      spent grain particles based on cell deposition (cell-to-carrier adhesion and cell
      to-cell attachment), immobilized cell growth, and immobilized biomass detachment
      (cell outgrowth, biofilm abrasion) was formulated. The concept of the active
      fraction of immobilized biomass (X(im)act) and the maximum attainable biomass
      load (X(im)max) was included into the model. Since the average biofilm thickness
      was estimated at ca. 10 microm, the limitation of the diffusion of substrates
      inside the yeast biofilm could be neglected. The model successfully predicted the
      dynamics of the immobilized cell growth, maximum biomass load, free cell growth,
      and glucose consumption under constant hydrodynamic conditions in a bubble-column
      reactor. Good agreement between model simulations and experimental data was
      achieved.

PMID- 15575707
TI  - Effect of pH on the ternary solution behavior of beta-lactoglobulin.
AB  - Ternary phase diagrams (TPDs) were constructed for aqueous beta-lactoglobulin
      solutions containing ethanol and (NH4)2SO4 at pHs of 7, 5, and 3 for temperatures
      between 20 and 70 degrees C. The addition of (NH4)2SO4 generally led to the
      production of a reversible precipitate, a transformation that was not strongly
      influenced by temperature or pH. In contrast, at pH 7 and 20 degrees C, ethanol
      concentrations >12% led to the formation of a molten-globule structure, which
      gelled at protein concentrations >10%. Destabilization of beta-lactoglobulin
      structure occurred at lower ethanol concentrations as temperature was increased,
      until at 70 degrees C, all solutions that were previously liquid at room
      temperature had transformed into a gel. At pH 5.0, near beta-lactoglobulin's
      isoelectric point, demixing dominated, leading to the creation of either
      irreversible precipitates or a paste-like microgel. Elevated temperatures caused
      the previously liquid morphology to transform into either a reversible aggregate
      or microgel. Solution behavior at pH 3 had characteristics of what was observed
      at pHs 7 and 5. At moderated protein and ethanol concentrations, a paste-like
      microgel was observed, whereas at higher ethanol concentrations, beta
      lactoglobulin formed a gel. This work demonstrates how small changes in protein
      structure at the molecular level can have a dramatic effect on macroscopic
      morphology.

PMID- 15575708
TI  - Expression and characterization of a His-tagged 11S seed globulin from Amaranthus
      hypochondriacus in Escherichia coli.
AB  - DNA encoding a His-tagged 11S globulin from Amaranthus hypochondriacus
      (amarantin) was successfully expressed in Escherichia coli strains BL21 (DE3) and
      Origami (DE3). The two strains produced different accumulation patterns. Whereas
      most of the proamarantin expressed in BL21 (DE3) was localized in inclusion
      bodies, that produced in Origami (DE3) was soluble (76 mg/L). Sucrose density
      gradient ultracentrifugation analysis of the expressed soluble proamarantin
      revealed that the protein was assembled into trimers. Treatment of proamarantin
      trimers in vitro using purified asparaginyl endopeptidase resulted in the
      appearance of peptides of the sizes expected for acidic and basic chains. Because
      the proamarantin assembles into trimers with the expected sedimentation
      characteristics and is cleaved into acidic and basic chains rather than being
      degraded, the results suggest that the protein folding occurring in E. coli is
      similar to that taking place in seeds. The His-tagged proamarantin was purified
      in a single step by immobilized metal affinity chromatography with a final yield
      of 48 mg/L. The overexpression of proamarantin in E. coli, together with the one
      step purification will facilitate further investigation of this storage protein
      through site-directed mutagenesis.

PMID- 15575709
TI  - Effect of process variables on supercritical fluid disruption of Ralstonia
      eutropha cells for poly(R-hydroxybutyrate) recovery.
AB  - This research focuses on the disruption of the gram-negative bacterium Ralstonia
      eutropha cells by supercritical CO2 for poly(R-hydroxybutyrate) (PHB) recovery.
      The variables affecting cell disruption such as drying strategy, type of
      modifier, and cultivation time, as well as operating pressure, temperature, and
      repeated release of supercritical CO2 pressure, have been studied. Effect of this
      disruption technique on PHB molecular mass was also investigated. PHB recovery
      was examined using a combination of this method and chemical pretreatments. For
      salt pretreatment, the cells were exposed to 140 mM NaCl and heat (60 degrees C,
      1 h). The cells were also exposed to 0.2-0.8% (w/w) NaOH to examine the effect of
      alkaline pretreatment. Bacterial cells treated in growth phase exhibited less
      resistance to disruption than nutrient-limited cells in the stationary phase. It
      was also found that the wet cells could be utilized to recover PHB, but purity of
      the product was lower than that obtained from freeze-dried cells. Pretreatment
      with a minimum of 0.4% (w/w) NaOH was necessary to enable complete disruption
      with two times pressure release. Salt pretreatment was less effective; however,
      disruption was improved by the application of alkaline shock. The proposed method
      is economic and comparable with other recovery methods in terms of the percentage
      of PHB recovery and energy consumption, while it is environmentally more benign.

PMID- 15575710
TI  - Reduced oxygen supply increases process stability and product yield with
      recombinant Pichia pastoris.
AB  - A single-chain antibody fragment directed against fimbriae of enterotoxigenic
      Escherichia coli was produced by recombinant Pichia pastoris under control of the
      methanol-inducible AOX1 promoter. In high-cell-density cultivation on defined
      medium, methanol-limited and methanol-saturated conditions were compared. After
      batch and fed-batch phase on glycerol, the methanol concentration was controlled
      to 1% (v/v) or methanol was fed with an exponentially increasing rate. Whereas
      methanol limitation impaired cell integrity and product quality, finally yielding
      no active product as a result of degradation, oxygen limitation was acceptable.
      To postpone the onset of limitation, the inlet air was enriched by pure oxygen.
      Because of faster methanol consumption, however, the process became sensitive to
      fluctuations in the feeding rate, and complete arrest of metabolism encountered
      upon small perturbations shortened the active production period. Without
      additional oxygen supply, the process was robust. Loss of culture integrity was
      monitored by flow cytometry and was found to precede changes in metabolic rates;
      it can thus serve as a sensitive indicator of forthcoming problems. Single-step
      downstream processing from the culture supernatant by His-affinity chromatography
      was efficient when antifoam agent that coagulates upon pH titration was omitted
      and yielded 1 g of purified lyophilized product from 6 L initial culture volume.

PMID- 15575711
TI  - Sequence-specific oligonucleotide purification using peptide nucleic acid
      amphiphiles in hydrophobic interaction chromatography.
AB  - We present a methodology to perform sequence-specific separations of
      oligonucleotides using peptide nucleic acids covalently linked to alkane chains,
      or "PNA amphiphiles (PNAAs)". The PNAA/DNA duplexes are discriminated from
      unbound DNA using hydrophobic interaction chromatography on a phenyl-substituted
      Sepharose column. Nearly quantitative recovery is achieved at concentrations of
      50 microM after incubation of oligomers with a stoichiometric amount of PNAA for
      1 min or so. The method exhibits high sequence specificity, selectivity, and
      resolution when applied to mixtures of various oligomers up to 60 base pairs in
      length.

PMID- 15575712
TI  - Direct refolding of inclusion bodies using reversed micelles.
AB  - The protein refolding of inclusion bodies was investigated using reversed
      micelles formed by aerosol OT (AOT). Ribonuclease A (RNase A) was overexpressed
      in Escherichia coli and used as native inclusion bodies. The enzymatic activity
      of RNase A was completely regained from the inclusion bodies within 14 h by
      solubilization in reversed micelles. To further enhance the refolding rate, a
      molecular chaperone, GroEL, was incorporated into the refolding system. The
      resultant refolding system including GroEL showed better performance under
      optimized conditions for the refolding of RNase A inclusion bodies. The refolding
      rate was considerably improved by the addition of the molecular chaperone, and
      the refolding step was completed in 1 h. The protein refolding in the GroEL
      containing refolding system was strongly dependent on the coexistence of ATP and
      Mg2+, suggesting that the GroEL hosted in the reversed micelles was biologically
      active and assisted in the renaturation of the inclusion bodies. The addition of
      cold acetone to the reversed micellar solution allowed over 90% recovery of the
      renatured RNase A.

PMID- 15575713
TI  - High-level scu-PA production by butyrate-treated serum-free culture of
      recombinant CHO cell line.
AB  - The MGpUK-5 cell line, transformed with a single-chain urokinase-type plasminogen
      activator (scu-PA) minigene, generated mRNA transcripts and scu-PA titers
      corresponding to 65% or 86% of the amount generated before serum-free adaptation,
      despite significant loss of scu-PA gene copies during adaptation to serum-free
      culture. To further augment scu-PA production, a culture strategy employing
      sodium butyrate was explored. In 60-mL spinner flask cultures, sodium butyrate in
      the concentration range 1-10 mM allowed scu-PA production 2- to 3-fold higher
      than that in the negative control culture. Its productivity-enhancing activity
      was dependent on cell density in a range of 1-5 x 10(6) cells/mL, generating
      72,200 +/- 8,100 IU/mL (480 +/- 50 mg/L) in 60-mL spinner flask cultures. To
      confirm this result, cells were grown to 4.4 x 10(6) cells/mL and treated with 5
      mM sodium butyrate in a 2.5-L perfusion culture. The scu-PA titer increased more
      than 2-fold, and specific production rate of scu-PA increased 3-fold by this
      treatment. Overall, this perfusion culture gave rise to 1.7 x 10(8) IU scu-PA
      (1.1 g), comparable to total scu-PA production in a batch butyrate-treated
      culture performed at a 25-L bioreactor scale (1.3-3.5 g). Our results suggest
      that sodium butyrate treatment on high-density culture enables scu-PA production
      in gram quantities.

PMID- 15575714
TI  - Biodegradable PLGA microcarriers for injectable delivery of chondrocytes: effect
      of surface modification on cell attachment and function.
AB  - Poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by an
      oil/water emulsion solvent evaporation method to use as an injectable
      microcarrier for cell delivery. Three different kinds of PLGA microspheres having
      hydrophobic, negatively charged, and positively charged surfaces were prepared.
      Hydrophobic and negatively charged PLGA microspheres were prepared by using
      terminally capped and uncapped PLGA polymer, respectively. Positively charged
      PLGA microspheres were prepared by blending PLGA with PLGA-g-poly(L-lysine) graft
      copolymer as a surface modifying agent. Bovine chondrocytes were cultured on the
      three PLGA microspheres under serum conditions to comparatively evaluate cell
      attachment, cell proliferation, and cell function with respect to surface
      properties. Positively charged PLGA microspheres showed the highest cell
      attachment, growth, and function compared to hydrophobic and negatively charged
      microspheres. Surface-modified PLGA microspheres can potentially be used as an
      injectable delivery system for cells into a tissue defect site.

PMID- 15575715
TI  - A novel rotating-shaft bioreactor for two-phase cultivation of tissue-engineered
      cartilage.
AB  - A novel rotating-shaft bioreactor (RSB) was developed for two-phase cultivation
      of tissue-engineered cartilage. The reactor consisted of a rotating shaft on
      which the chondrocyte/scaffold constructs (7.5 mm diameter x 3.5 mm thickness)
      were fixed and a reactor vessel half-filled with medium. The horizontal rotation
      of the shaft resulted in alternating exposure of the constructs to gas and liquid
      phases, thus leading to efficient oxygen and nutrient transfer, as well as
      periodically changing, mild shear stress exerting on the construct surfaces (0
      0.32 dyn/cm2 at 10 rpm), as revealed by computer simulation. Strategic operation
      of the RSB (maintaining rotating speed at 10 rpm for 3 weeks and lowering the
      speed to 2 rpm in week 4) in combination with higher seeding density (6 x 10(6)
      chondrocytes/scaffold) and medium perfusion resulted in uniform cell distribution
      and increased glycosaminoglycan (3.1 mg/scaffold) and collagen (7.0 mg/scaffold)
      deposition. The 4-week constructs resembled native cartilages in terms of not
      only gross appearance and cell morphology but also distributions of
      glycosaminoglycan, total collagen, and type II collagen, confirming the
      maintenance of chondrocyte phenotype and formation of cartilage-like constructs
      in the RSB cultures. In summary, the novel RSB may be implicated for in vitro
      study of chondrogenesis and de novo cartilage development under periodic
      mechanical loading. With proper optimization of the culture conditions, a RSB may
      be employed for the production of cartilage-like constructs.

PMID- 15575716
TI  - Lentiviral vectors pseudotyped with envelope glycoproteins derived from human
      parainfluenza virus type 3.
AB  - We describe the generation of lentiviruses pseudotyped with human parainfluenza
      type 3 envelope (HPIV3) glycoproteins. Lentivirus particles, expressed in 293T/17
      cells, incorporate HPIV3 hemagglutinin-neuraminidase (HN) and fusion (F) proteins
      into their lipid bilayers and are able to transduce human kidney epithelial cells
      and polarized MDCK cells. Neuraminidase, AZT, and anti-HPIV3 antisera block
      transduction, which is consistent with lentiviral-mediated transduction via
      sialated receptors for HPIV3. Our findings show that HPIV3 pseudotyped
      lentiviruses can be formed and may have a number of useful properties for human
      gene transfer.

PMID- 15575717
TI  - Immobilization of Candida bombicola cells on free-standing organic-gold
      nanoparticle membranes and their use as enzyme sources in biotransformations.
AB  - Preparation of chemically functionalized biocompatible surfaces is of current
      interest, with application in the immobilization of various bioactive species
      such as DNA, enzymes, whole cells, etc. We report herein the one-step synthesis
      of a self-supporting gold nanoparticle membrane, its surface modification, and
      application in the immobilization of Candida bombicola (yeast) cells. The gold
      nanoparticle membrane is prepared by the spontaneous reduction of aqueous
      chloroaurate ions by a diamine at a liquid-liquid interface. The gold
      nanoparticles in the polymeric membrane may be capped with octadecylamine (ODA)
      molecules, thereby rendering the nanoparticle membrane hydrophobic. Exposure of
      the hydrophobized organic-gold nanoparticle membrane to C. bombicola yeast cells
      results in their binding to the membrane, possibly through nonspecific
      interactions such as hydrophobic interactions between the yeast cell walls and
      the ODA molecules. The enzyme cytochrome P450 present in the yeast cells
      immobilized on the organic-gold nanoparticle membrane was then used in the
      transformation of the arachidonic acid (AA) to sophorolipids followed by acid
      hydrolysis to form 20-hydroxyeicosatetraneoic acid (20-HETE). The organic-gold
      nanoparticle membrane-C. bombicola bioconjugate could be easily separated from
      the reaction medium and reused a number of times.

PMID- 15575718
TI  - Flexible automation of cell culture and tissue engineering tasks.
AB  - Until now, the predominant use cases of industrial robots have been routine
      handling tasks in the automotive industry. In biotechnology and tissue
      engineering, in contrast, only very few tasks have been automated with robots.
      New developments in robot platform and robot sensor technology, however, make it
      possible to automate plants that largely depend on human interaction with the
      production process, e.g., for material and cell culture fluid handling,
      transportation, operation of equipment, and maintenance. In this paper we present
      a robot system that lends itself to automating routine tasks in biotechnology but
      also has the potential to automate other production facilities that are similar
      in process structure. After motivating the design goals, we describe the system
      and its operation, illustrate sample runs, and give an assessment of the
      advantages. We conclude this paper by giving an outlook on possible further
      developments.

PMID- 15575719
TI  - Detecting changes in the relative expression of KRAS2 splice variants using
      polymerase colonies.
AB  - Because splice variants of a gene with multiple isoforms give rise to proteins
      with different functions, it seems plausible that changes in the expression
      levels of the splice variants could be a contributing factor to disease. In fact,
      recent examples in the literature clearly illustrate that altered expression
      levels of splice variants may play an important role in disease. Furthermore,
      these works demonstrate that changes in expression levels could potentially be
      used to (1) monitor disease progression, (2) diagnose disease, and/or (3)
      determine disease state. In this work an immobilized form of PCR, known as polony
      technology, was adapted to quantify the relative expression levels of splice
      variants. Specifically, the relative expression levels of the two splice variants
      of the oncogene K-ras, namely, K-RAS2A and K-RAS2B, were determined using polony
      technology.

PMID- 15575720
TI  - Enhancing the reusability of endoglucanase-gold nanoparticle bioconjugates by
      tethering to polyurethane microspheres.
AB  - The synthesis of polyurethane microsphere-gold nanoparticle "core-shell"
      structures and their use in the immobilization of the enzyme endoglucanase are
      described. Assembly of gold nanoparticles on the surface of polymer microspheres
      occurs through interaction of the nitrogens in the polymer with the
      nanoparticles, thereby precluding the need for modifying the polymer microspheres
      to enable such nanoparticle binding. Endoglucanse could thereafter be bound to
      the gold nanoparticles decorating the polyurethane microspheres, leading to a
      highly stable biocatalyst with excellent reuse characteristics. The immobilized
      enzyme retains its biocatalytic activity and exhibits improved thermal stability
      relative to free enzyme in solution. The high surface area of the host gold
      nanoparticles renders the immobilized enzyme "quasi free", while at the same time
      retaining advantages of immobilization such as ease of reuse, enhanced temporal
      and thermal stability, etc.

PMID- 15575721
TI  - A recombinant glutamine-binding protein from Escherichia coli: effect of ligand
      binding on protein conformational dynamics.
AB  - We have investigated the effect of the binding of glutamine on the conformational
      dynamics of the recombinant glutamine binding protein (GlnBP) from Escherichia
      coli by steady-state and time-resolved fluorescence techniques. The structural
      stability of the protein was also studied by far-UV circular dichroism
      spectroscopy in the range of temperature between 25 and 80 degrees C. The results
      showed that the interaction of the protein with the ligand resulted in a marked
      change of the structural and conformational dynamics features of the protein. In
      particular, the fluorescence and circular dichroism data showed that the presence
      of glutamine resulted in a dramatic increase of the protein thermal stability of
      about 10 degrees C. In addition, the fluorescence time-resolved data pointed out
      that both in the absence and in the presence of glutamine the protein structure
      was highly rigid with small amplitude of segmental motion up to 65 degrees C and
      a low accessibility of the protein tryptophan residues to acrylamide. The
      obtained results on the structural properties of the recombinant glutamine
      binding protein in the absence and in the presence of glutamine can contribute to
      a better understanding of the transport-related functions of the protein and
      structurally similar periplasmic transport proteins, as well as to the design and
      development of new biotechnological applications of this class of proteins.

PMID- 15575722
TI  - DNA polymerase-catalyzed elongation of repetitive hexanucleotide sequences:
      application to creation of repetitive DNA libraries.
AB  - We demonstrate the elongation of various hexanucleotide sequences with
      thermophilic DNA polymerase, under isothermal or thermal cyclic reaction
      conditions. We prepared 10 types of double repeat hexanucleotide duplexes with
      various GC compositions containing between 0 and 6 GC nucleotides per repeat and
      incubated these duplexes with thermophilic Taq DNA polymerase and dNTPs at
      various temperatures. All of the model repetitive short duplexes were elongated
      under the isothermal incubation conditions, although there were some differences
      in the elongation efficiencies derived from the GC composition in the repetitive
      sequences. It was also found that all of the model repetitive duplexes were
      extended more effectively by a 3-step thermal cyclic reaction involving
      denaturation, annealing, and extension. On the basis of this technique, we
      prepared a glutamate-encoding short repetitive duplex and created long repetitive
      DNAs under isothermal and thermal cyclic reaction conditions. DNA sequencing
      analysis of the cloned repetitive DNA revealed that well-ordered long repetitive
      DNAs of various chain lengths were created by this DNA polymerase-catalyzed
      ligation method, and these were easily cloned into vectors by the TA-cloning
      method. This method could be useful for obtaining DNAs encoding arbitrary long
      repetitive amino acid sequences more effectively than the conventional T4 ligase
      catalyzed ligation method.

PMID- 15575723
TI  - Operational regimes for a simplified one-step artificial chaperone refolding
      method.
AB  - The "artificial chaperone method" for protein refolding developed by Rozema et
      al. (Rozema, D.; Gellman, S. H. J. Am. Chem. Soc. 1995, 117 (8), 2373-2374)
      involves the sequential dilution of denatured protein into a buffer containing
      detergent (cetyltrimethylammonium bromide, CTAB) and then into a refolding buffer
      containing cyclodextrin (CD). In this paper a simplified one-step artificial
      chaperone method is reported, whereby CTAB is added directly to the denatured
      solution, which is then diluted directly into a refolding buffer containing beta
      cyclodextrin (beta-CD). This new method can be applied at high protein
      concentrations, resulting in smaller processing volumes and a more concentrated
      protein solution following refolding. The increase in achievable protein
      concentration results from the enhanced solubility of CTAB at elevated
      temperatures in concentrated denaturant. The refolding yields obtained for the
      new method were significantly higher than for control experiments lacking
      additives and were comparable to the yields obtained with the classical two-step
      approach. A study of the effect of beta-CD and CTAB concentrations on refolding
      yield suggested two operational regimes: slow stripping (beta-CD/CTAB
      approximately 1), most suited for higher protein concentrations, and fast
      stripping (beta-CD/CTAB approximately 2.7), best suited for lower protein
      concentrations. An increased chaotrope concentration resulted in higher refolding
      yields and an enlarged operational regime.

PMID- 15575724
TI  - Oxidation of chlorophenols catalyzed by Coprinus cinereus peroxidase with in situ
      production of hydrogen peroxide.
AB  - Degradation of 2,6-dichlorophenol (2,6-DCP) was accomplished by oxidation
      catalyzed by Coprinus cinereus peroxidase. Immobilization of the enzyme in a
      polyacrylamide matrix enhanced DCP oxidation. Hydrogen peroxide, peroxidase's
      natural substrate, was produced enzymatically in situ to avoid peroxidase
      inactivation by its too high concentration. In the case of larger scale
      utilization, the method would also avoid direct handling of this hazardous
      reagent.

PMID- 15575725
TI  - Pressurized hot water extraction of anthraquinones from the roots of Morinda
      citrifolia.
AB  - This study examines pressurized hot water extraction of anthraquinones from dried
      roots of Morinda citrifolia (Noni). The effects of various operating conditions
      such as water temperature (110, 170, and 220 degrees C), and water flow rate (2,
      4, and 6 mL min(-1)) on extraction yield and extraction rate were determined. At
      220 degrees C, the extraction yield was the highest and was approximately 43.6 mg
      g(-1). Subcritical water extraction at 4 mL min(-1) or higher was found to be
      able to recover all the antraquinones present in the roots within 3 h of
      extraction, even at 170 degrees C. Pressure had no significant effect on the
      results for the range of temperatures studied. The flow rate of 6 mL min(-1)
      resulted in the highest extraction rate, but the extraction efficiency, as
      measured by the amount of anthraquinones extracted per unit volume of water was
      lower than that of 4 mL min(-1). Anthraquinones solubility in pressurized hot
      water was determined. The results indicate a presence of a mass transfer
      limitation in the extraction process from solid matrix.

PMID- 15575726
TI  - Lactosucrose bioconversion from lactose and sucrose by whole cells of
      Paenibacillus polymyxa harboring levansucrase activity.
AB  - Lactosucrose, a functional trisaccharide, was produced from lactose as an
      acceptor and sucrose as a fructosyl donor by whole cells harboring
      transfructosylation activity of levansucrase. Levansucrase-induced cells of
      Paenibacillus polymyxa were obtained in the medium containing sucrose, and the
      transfructosylation activity in the whole cell was optimized for lactosucrose
      production. The optimal cell concentration, substrates ratio, temperature, and pH
      were 2.0% (w/v), 22.5% (w/v) lactose and 22.5% (w/v) sucrose, 55 degrees C, and
      6.0, respectively. Under these conditions, the whole cells produced approximately
      17.0% (w/v) lactosucrose in 6 h of reaction time with a productivity of 2.8%
      (w/v)/h.

PMID- 15575727
TI  - Extractive cultivation of xylanase by Penicillium janthinellum in a poly(ethylene
      glycol)/cashew-nut tree gum aqueous two-phase system.
AB  - Cultivation of the fungus Penicillium janthinellum for xylanase production was
      studied in a poly(ethylene glycol)/cashew-nut tree gum aqueous two-phase system,
      using a two-level fractional factorial design. The parameters studied were
      initial pH, cultivation time, type of agro-industrial residue (oat husk or corn
      cob), agitation, temperature, and phase-forming polymers. The xylanase produced
      during fermentation partitioned into the top phase. The agitation and temperature
      (negative), cultivation time and initial pH (positive) effects proved
      statistically significant for xylanase production. The highest percentage yield
      of the xylanase in the top and its production in the top phase, about 97% and
      160.7 U/mL, were obtained in cultures of 120 h, 40 rpm, 25 degrees C, and pH 5.0.

PMID- 15575728
TI  - Effect of supercritical fluids on C11beta-hydroxylation activity of Absidia
      coerulea.
AB  - The viability and C11beta-hydroxylation activity of Absidia coerulea were
      measured after treatment with compressed or supercritical CO2 and C2H4 under
      various initial pH and temperature conditions. The specific activity of A.
      coerulea on C11beta-hydroxylation can reach 23% and 75%, respectively, after
      treatment with 7.5 MPa of CO2 and C2H4, leading to the feasibility of enhancing
      both the solubility of the reactants and the beta-hydrocortisone yield for the
      hydroxylation of Reichsterin's substance acetate by using supercritical C2H4 as
      an alternative to the organic solvent.

PMID- 15575729
TI  - Temperature effects on product-quality-related enzymes in batch CHO cell cultures
      producing recombinant tPA.
AB  - Culture conditions that affect product quality are important to the successful
      operation and optimization of bioreactors. Previous studies have demonstrated
      that enzymes, such as proteases and sialidases, accumulate in batch bioreactors.
      These enzymes are known to be detrimental to the quality of recombinant
      glycoproteins. Bioreactor temperature has been used to control cell growth and
      recombinant protein production rates. However, the effect of culture temperature
      on the production of proteases and sialidases has not been investigated. In this
      study, Chinese hamster ovary cells were cultured with a temperature profile that
      decreased from 37 to 34 degrees C over 8 days and with a constant temperature of
      37 degrees C. Analysis of extracellular protease activity indicated that two
      major proteases were present (50 and 69 kDa). The 50 kDa protease activity
      decreased similarly with time for both culture conditions. The 69 kDa protease
      activity increased with time for both culture conditions. The constant
      temperature cultures had significantly lower 69 kDa protease levels compared to
      the ramped-temperature cultures in the early stationary phase. Intracellular
      sialidase activity was present in both cultures. The intracellular sialidase
      activity increased dramatically for both culture conditions immediately after the
      cells were inoculated into fresh medium. The initial peak in intracellular
      sialidase activity was followed by a first-order decay. The intracellular
      sialidase activities for the two culture conditions were not significantly
      different. The production of recombinant tissue type plasminogen activator was
      not significantly different for the two culture conditions. Thus, the previously
      hypothesized advantages that lower culture temperatures have reduced protease
      activity and improved productivity do not appear to be universal.

PMID- 15575730
TI  - Laccase-mediator biobleaching applied to a direct yellow dyed paper.
AB  - A laccase-mediator system (LMS) for biobleaching was applied to a bleached
      chemical pulp dyed with stilbene dye Direct Yellow 11. Of mediators tested, 2,2'
      azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) was found to be more effective
      than either violuric acid (VA) or N-hydroxybenzotriazole (HBT), which had been
      shown to be superior to ABTS when bleaching virgin chemical pulp. The laccase
      ABTS system removed more than 60% of the color.

PMID- 15575731
TI  - Substituted 2-azabicyclo[2.1.1]hexanes as constrained proline analogues:
      implications for collagen stability.
AB  - Among the proteinogenic amino acids, only proline is a secondary amine and only
      proline has a saturated ring. Electronegative substituents on C-4 (that is,
      C(gamma)) have a substantial effect on the trans/cis ratio of the prolyl peptide
      bond and the pucker of the pyrrolidine ring. 2-Azabicyclo[2.1.1]hexane is, in
      essence, a proline analogue with two C(gamma) atoms, one in each of the two
      prevalent ring puckers of proline. Here, 2-azabicyclo[2.1.1]hexane analogues of
      2S-proline, (2S,4S)-4-hydroxyproline, and (2S,4S)-4-fluoroproline residues were
      synthesized, and their trans/cis ratios were shown to be invariant in a
      particular solvent. Thus, the substitution of a proline residue on C-4 affects
      the trans/cis ratio by altering the pucker of its pyrrolidine ring. This finding
      has implications for the conformation of collagen, which has an abundance of 2S
      proline and (2S,4R)-4-hydroxyproline residues, and can be stabilized by (2S,4R)-4
      fluoroproline and (2S,4S)-4-fluoroproline residues.

PMID- 15575732
TI  - From dimerization, to cycloaddition, to atom transfer cyclization: the further
      chemistry of TMM diradicals.
AB  - We describe [a] the first examples of intramolecular cycloaddition of a TMM diyl
      to a remotely tethered aldehyde, [b] the effect of a Lewis acid upon the course
      of TMM chemistry, [c] examples of exclusive intramolecular cycloaddition,
      competitive cycloaddition and ATC, and exclusive ATC, and [d] a set of predictive
      guidelines with which to assess whether cycloaddition or ATC will be the
      preferred path, and when the two processes will be competitive. Remarkably, a
      wide variety of structures can be obtained simply by varying the length of the
      tether within the diazenes investigated. DFT calculations were used to probe the
      energy surfaces for both atom transfer and cycloaddition. The transition
      structure for atom transfer involving the captodative system indicates that it
      occurs earlier along the reaction coordinate than for a system having only one
      radical stabilizing group. This is consistent with the existence of an exothermic
      process leading from the initial diyl to the captodatively stabilized distonic
      diyl. Gratifyingly, theory agrees with observation and provides substantial
      insight into the chemistry.

PMID- 15575733
TI  - A comparison of acetyl- and methoxycarbonylnitrenes by computational methods and
      a laser flash photolysis study of benzoylnitrene.
AB  - Density functional theory (DFT), CCSD(T), and CBS-QB3 calculations were performed
      to understand the chemical and reactivity differences between acetylnitrene
      (CH(3)C(=O)N) and methoxycarbonylnitrene (CH(3)OC(=O)N) and related compounds.
      CBS-QB3 theory alone correctly predicts that acetylnitrene has a singlet ground
      state. We agree with previous studies that there is a substantial N-O interaction
      in singlet acetylnitrene and find a corresponding but weaker interaction in
      methoxycarbonylnitrene. Methoxycarbonylnitrene has a triplet ground state because
      the oxygen atom stabilizes the triplet state of the carbonyl nitrene more than
      the corresponding singlet state. The oxygen atom also stabilizes the transition
      state of the Curtius rearrangement and accelerates the isomerization of
      methoxycarbonylnitrene relative to acetylnitrene. Acetyl azide is calculated to
      decompose by concerted migration of the methyl group along with nitrogen
      extrusion; the free energy of activation for this concerted process is only 27
      kcal/mol, and a free nitrene is not produced upon pyrolysis of acetyl azide.
      Methoxycarbonyl azide, on the other hand, does have a preference for stepwise
      Curtius rearrangement via the free nitrene. The bimolecular reactions of
      acetylnitrene and methoxycarbonylnitrene with propane, ethylene, and methanol
      were calculated and found to have enthalpic barriers that are near zero and free
      energy barriers that are controlled by entropy. These predictions were tested by
      laser flash photolysis studies of benzoyl azide. The absolute bimolecular
      reaction rate constants of benzoylnitrene were measured with the following
      substrates: acetonitrile (k = 3.4 x 10(5) M(-1) (s-1)), methanol (6.5 x 10(6) M(
      1) s(-1)), water (4.0 x 10(6) M(-1) s(-1)), cyclohexane (1.8 x 10(5) M(-1) s(
      1)), and several representative alkenes. The activation energy for the reaction
      of benzoylnitrene with 1-hexene is -0.06 +/- 0.001 kcal/mol. The activation
      energy for the decay of benzoylnitrene in pentane is -3.20 +/- 0.02 kcal/mol. The
      latter results indicate that the rates of reactions of benzoylnitrene are
      controlled by entropic factors in a manner reminiscent of singlet carbene
      processes.

PMID- 15575734
TI  - Complex peptidyl nucleoside antibiotics: efficient syntheses of the glycosyl
      nucleoside amino acid cores.
AB  - Employing an amino acid chiral template strategy, the present research describes
      a general and highly efficient protocol for the rapid construction of enantiopure
      furanosyl and pyranosyl nucleoside amino acid cores as present in various complex
      peptidyl nucleoside antibiotics. Starting from easily available d-serine, the
      strategy and the approach involve rapid and efficient stereoselective synthesis
      of five- or six-membered lactone amino alcohols, followed by incorporation of the
      required functionalities of the target molecules on these strategically
      functionalized chiral templates.

PMID- 15575735
TI  - Saludimerines A and B, novel-type dimeric alkaloids with stereogenic centers and
      configurationally semistable biaryl axes.
AB  - The first biarylic bis-morphinanedienone alkaloids, saludimerines A (3a) and B
      (3b), isolated from a tree of Croton flavens (Euphorbiaceae) are described. These
      naturally occurring dimers of the known alkaloid salutaridine are joined together
      via a rotationally hindered biaryl axis, giving rise to atropo-diastereomers that
      are configurationally stable at room temperature but slowly interconvert in
      methanolic solution within several days. Their structures were established by
      spectroscopic methods and by partial synthesis, which was achieved by a highly
      atropo-diastereoselective biomimetic oxidative coupling of the monomeric
      precursor, salutaridine. Their axial configurations were elucidated by circular
      dichroism (CD) investigations, which succeeded despite the fact that the two
      atropo-diastereomers exhibit near-identical CD spectra. This remarkable
      phenomenon was rationalized by quantum chemical CD calculations. The
      configurational assignment of saludimerines A (3a) as P-axial and B (3b) as M was
      corroborated by atropisomer-specific NOE interactions between protons of the one
      molecular half with nuclei in the other.

PMID- 15575736
TI  - Reversible chemistry of CO2 in the preparation of fluorescent supramolecular
      polymers.
AB  - The chemistry between CO(2) and primary amines was used to construct novel types
      of supramolecular polymers and networks. Fluorescent self-assembling gel 2 was
      prepared, which employs both hydrogen bonding and dynamic, thermally reversible
      carbamate bonds. As precursors, biscalixarenes 1, 3, 4, 6, and 7 were
      synthesized, which strongly aggregate (K(D) > or = 10(6) M(-1) per capsule) in
      apolar solution with the formation of linear self-assembling polymers. Polymer 1n
      possesses CO(2)-philic primary amino groups on the periphery. CO(2) rapidly
      reacts with chains 1n in apolar solvents and cross-links them with the formation
      of multiple carbamate salt bridges. Three-dimensional polymeric network 2 was
      characterized by (13)C NMR spectroscopy and SEM. Addition of competitive solvent
      breaks hydrogen bonding in 2 but does not influence the carbamate linkers.
      Carbamate salt 9 was obtained. On the other hand, thermal release of CO(2) from 2
      and 9 was easily accomplished (1 h, 100 degrees C) with retaining the hydrogen
      bonding capsules. Thus, three-dimensional polymeric networks 2 were transformed
      back to linear polymeric chains 1n without their breakup. Multiple pyrene
      fluorophores, attached on the periphery of 2, cause strong fluorescence of the
      gel with benzene. When approximately 5% nitrobenzene was gelated together with
      benzene, fluorescence strongly decreases due to the energy transfer from the
      pyrene donors in gel 2 to trapped nitrobenzene molecules. This opens a way to
      switchable fluorescent materials.

PMID- 15575737
TI  - Geometrical effects on the intramolecular quenching of pi,pi* aromatic ketones by
      phenols and indoles.
AB  - Laser flash photolysis of a series of bichromophoric compounds 1-12 containing
      the 2-benzoylthiophene (BT) and phenol (PhOH) or indole (InH) moieties has been
      used to determine the possible geometrical effects in the intramolecular
      quenching of triplet excited ketones, resulting in formal hydrogen abstraction.
      The results are compared with those obtained in the intermolecular process. In
      both cases, substitution either at the thienyl or the phenyl moiety has a marked
      influence on the photoreactivity. Time-resolved experiments showed that the rate
      constants for bimolecular quenching by phenol and indole of 2-benzoylthiophene
      substituted at the thienyl 5-position were lower than those for BT substituted at
      the phenyl p-position, which agrees with the higher energy found for the excited
      triplet state of the latter compounds. However, the rate constant for hydrogen
      abstraction in the bichromophoric compounds by the pi,pi* triplet state of the
      derivatives with the spacer linked to the thienyl 5-position are higher than
      those of their regioisomers. These results indicate a possible geometry
      dependence in the intramolecular quenching process. Theoretical DFT studies have
      been carried out in order to estimate the optimum conformation for hydrogen
      abstraction in two pairs of phenolic and indolic bichromophoric regioisomers. The
      energy profile for photoactivation/deactivation of the aromatic ketone and the
      structures of the triplet states and biradicals involved in the process have been
      determined. The observed regiodifferentiation in the experimental studies is
      consistent with a dependence of the rate constant on orbital overlap between the
      carbonyl oxygen and the X-H bonds.

PMID- 15575738
TI  - Productive chloroarene C-cl bond activation: palladium/phosphine-catalyzed
      methods for oxidation of alcohols and hydrodechlorination of chloroarenes.
AB  - The palladium/phosphine-catalyzed productive chloroarene C-Cl bond activation
      provides general, efficient, and functional group friendly methods for the
      selective oxidation of alcohols and the hydrodechlorination of chloroarenes.

PMID- 15575739
TI  - Computational study on hydroxybenzotriazoles as reagents for ester hydrolysis.
AB  - 1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate
      potent esterolytic activity toward activated esters such as p-nitrophenyl
      diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic
      micelles at pH 8.2 and 25 degrees C. The deprotonated anionic forms of such
      reagents act as reactive species in the hydrolysis of ester. To rationalize the
      origin of their nucleophilic character, a detailed ab initio/DFT computational
      study has been performed on 1-5 along with additional hydroxybenzotriazole
      derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their
      corresponding bases are discussed in detail. All calculations were carried out
      using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab
      initio/DFT (B3LYP) using 6-31G and 6-31+G basis sets. Free energy of protonation
      ("fep") of the 1-hydroxybenzotriazoles (1-13), free energy of solvation
      DeltaG(aq), and the corresponding pK(a) values have been calculated. Solvation
      free energies were calculated using density functional theory and the polarizable
      continuum model. In addition, to examine the reliability of calculated fep,
      benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been
      computed as reference systems using different methods and basis sets, the
      experimental feps of which are known. Our experimental finding shows that the
      compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP
      and PNPH. This has been predicted from our calculated fep, pK(a), and natural
      charge analysis results as well. In general, the introduction of electron
      withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of
      pK(a) and fep. As the pK(a) values are lowered, a greater percentage of such
      hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2.
      Since the anionic forms are nucleophilic, pK(a) lowering should enhance their
      ester cleaving capacity. However, such substitution also decreases the charge
      density on the catalytically active oxido atom (O(7)). Taking these two factors
      together, the derivatives are only modestly better nucleophiles in comparison to
      the parent 1-hydroxybenzotriazole. Interestingly, the introduction of electron
      donating groups does not significantly enhance the charge accumulation on the
      oxido atom (O(7)) of 1-hydroxybenzotriazoles.

PMID- 15575740
TI  - Synthesis of nonracemic allylic hydroxy phosphonates via alkene cross metathesis.
AB  - Allylic hydroxy phosphonates and their derivatives can be interconverted by using
      cross metathesis with second generation Grubbs catalyst. The absolute
      stereochemistry of the starting phosphonate is conserved in the product. Cross
      metathesis reaction of the acrolein-derived phosphonate 2a yields a series of
      functionalized allylic hydroxy phosphonates. However, the cross metathesis
      reaction is often accompanied by competing dimerization and alkene migration
      reactions leading to a reduction in yield. The cinnamaldehyde- and crotonaldehyde
      derived phosphonates 2b and 2c were also examined. In general, the metathesis
      reactions of phosphonates 2b and 2c are considerably slower than those for
      phosphonate 2a leading to mixtures. Several hydroxyl-protected derivatives of the
      phosphonate 2a (methyl carbonate 3a, acetate 4a, N-tosyl carbamate 5a, TBDMS 6a,
      and acetoacetate 7a) undergo metathesis without competing side reactions to give
      substituted allylic phosphonates in good to excellent yield.

PMID- 15575741
TI  - Ring expansion-annulation strategy for the synthesis of substituted azulenes and
      oligoazulenes. 2. Synthesis of azulenyl halides, sulfonates, and azulenylmetal
      compounds and their application in transition-metal-mediated coupling reactions.
AB  - A "ring expansion-annulation strategy" for the synthesis of substituted azulenes
      is described based on the reaction of beta'-bromo-alpha-diazo ketones with
      rhodium carboxylates. The key transformation involves an intramolecular Buchner
      reaction followed by beta-elimination of bromide, tautomerization, and in situ
      trapping of the resulting 1-hydroxyazulene as a carboxylate or triflate ester.
      Further synthetic elaboration of the azulenyl halide and sulfonate annulation
      products can be achieved by employing Heck, Negishi, Stille, and Suzuki coupling
      reactions. Reaction of the azulenyl triflate 84 with pinacolborane provides
      access to the azulenylboronate 91, which participates in Suzuki coupling
      reactions with alkenyl and aryl iodides. The application of these coupling
      reactions to the synthesis of biazulenes, terazulene 101, and related
      oligoazulenes is described, as well as the preparation of the azulenyl amino acid
      derivative 110.

PMID- 15575742
TI  - Pyrrolodiazines. 6. Palladium-catalyzed arylation, heteroarylation, and amination
      of 3,4-dihydropyrrolo[1,2-a]pyrazines.
AB  - The palladium-catalyzed Suzuki cross-coupling reaction of arylboronic acids and 6
      bromo- and 6,8-dibromo-3,4-dihydropyrrolo[1,2-a]pyrazines afforded 6-substituted
      and 6,8-disubstituted 3,4-dihydropyrrolo[1,2-a]pyrazines in good yields. Stille
      and Negishi coupling reactions have been used to prepare 6-heteroaryl-substituted
      derivatives in moderate yields by employing heteroaryl halides and 6-metalated
      3,4-dihydropyrrolo[1,2-a]pyrazines as reaction partners. A variety of cyclic
      secondary amines have also been incorporated at position C-6 of 6-bromo-1-phenyl
      3,4-dihydropyrrolo[1,2-a]pyrazine in the presence of the palladium catalyst
      Pd(2)(dba)(3) in conjunction with BINAP as ligand. This amination reaction is one
      of the few reported examples of such a palladium-catalyzed transformation on a
      pyrrole ring, although the reaction could not be extended to less nucleophilic
      amines.

PMID- 15575743
TI  - Remarkable substituent effects on the oxidizing ability of triarylbismuth
      dichlorides in alcohol oxidation.
AB  - Substituent effects on the oxidizing ability of triarylbismuth dichlorides were
      examined by intermolecular and intramolecular competition experiments on geraniol
      oxidation in the presence of DBU. It was found that the oxidizing ability of the
      dichlorides increases with increasing electron-withdrawing ability of the para
      substituents, and by introduction of a methyl group at the ortho position of the
      aryl ligands attached to the bismuth. The intermolecular and intramolecular H/D
      kinetic isotope effects observed for the competitive oxidation of p-bromobenzyl
      alcohols indicate that the rate-determining step involves C-H bond cleavage.
      Several primary and secondary alcohols were oxidized efficiently under mild
      conditions by the combined use of newly developed organobismuth(V) oxidants and
      DBU.

PMID- 15575744
TI  - Conjugate additions to phenylglycinol-derived unsaturated delta-lactams.
      Enantioselective synthesis of uleine alkaloids.
AB  - The stereochemical outcome of the conjugate addition of a variety of stabilized
      nucleophiles (2-indoleacetic enolates and sulfur-stabilized anions) to the
      phenylglycinol-derived unsaturated lactams trans-2, cis-2, and its 8-ethyl
      substituted analogue 10 is studied. The factors governing the exo or endo facial
      stereoselectivity are discussed. This methodology provides short synthetic routes
      to either cis- or trans-3,4-disubstituted enantiopure piperidines as well as
      efficient routes for the enantioselective construction of the tetracyclic ring
      system of uleine alkaloids, both in the normal and 20-epi series. The formal
      total synthesis of several alkaloids of this group is reported.

PMID- 15575745
TI  - A total synthesis of hydroxylysine in protected form and investigations of the
      reductive opening of p-methoxybenzylidene acetals.
AB  - A synthesis of (2S,5R)-5-hydoxylysine, based on (R)-malic acid and Williams
      glycine template as chiral precursors, has been developed. This afforded
      hydroxylysine, suitably protected for direct use in peptide synthesis, in 32%
      yield over the 13-step sequence. Regioselective reductive opening of a p
      methoxybenzylidene acetal and alkylation of the Williams glycine template were
      key steps in the synthetic sequence. Surprisingly, the regioselectivity in
      opening of the p-methoxybenzylidene acetal was reversed as compared to what was
      expected. It was found that this was due to chelation of the trialkylsilyl
      choride, used as an electrophile in the reductive opening, to an adjacent azide
      functionality. It was also discovered that an equivalent amount of trialkylsilyl
      hydride was formed in the reaction, a finding that led to additional mechanistic
      insight into reductive openings of p-methoxybenzylidene acetals with sodium
      cyanoborohydride as reducing agent.

PMID- 15575746
TI  - Regio- and stereoselectivity of the addition of O-, S-, N-, and C-nucleophiles to
      the beta vinyl oxirane derived from D-glucal.
AB  - 6-O-Trityl- (1a) and 6-(O-benzyl)-substituted epoxide (1b) derived from D-glucal
      were examined in their addition reactions with O-, C-, N-, and S-nucleophiles. A
      1,4-regio- and beta-stereoselective or an anti 1,2-addition pathway is commonly
      observed depending on the ability of the nucleophile to coordinate with the
      oxirane oxygen. When TMSN(3) or LiN(3) are used as azide-based nucleophiles, a
      1,2-syn-addition pathway is also observed.

PMID- 15575747
TI  - Determination of absolute configuration using density functional theory
      calculation of optical rotation: chiral alkanes.
AB  - The recently developed Gauge-Invariant (Including) Atomic Orbital (GIAO) based
      Time-Dependent Density Functional Theory (TDDFT) methodology for the calculation
      of transparent spectral region optical rotations of chiral molecules provides a
      new approach to the determination of absolute configurations. Here, we discuss
      the application of the TDDFT/GIAO methodology to chiral alkanes. We report
      B3LYP/aug-cc-pVDZ calculations of the specific rotations of the 22 chiral
      alkanes, 2-23, of well-established Absolute Configuration. The average absolute
      deviation of calculated and experimental [alpha](D) values for molecules 2-22 is
      24.8. In two of the molecules 2-23, trans-pinane, 10, and endo-isocamphane, 13,
      the sign of [alpha](D) is incorrectly predicted. Our results demonstrate that
      absolute configurations of alkanes can be reliably assigned by using B3LYP/aug-cc
      pVDZ TDDFT/GIAO calculations if, but only if, [alpha](D) is significantly greater
      than 25. In the case of (-)-anti-trans-anti-trans-anti-trans
      perhydrotriphenylene, 1, [alpha](D) is -93 and TDDFT/GIAO calculations reliably
      lead to the absolute configuration R(-).

PMID- 15575748
TI  - On the dichotomic behavior of the Z-2,4-dinitrophenylhydrazone of 5-amino-3
      benzoyl-1,2,4-oxadiazole with acids in toluene and in dioxane/water:
      rearrangement versus hydrolysis.
AB  - The mononuclear rearrangement (MRH) of the Z-2,4-dinitrophenylhydrazone (4a) and
      of the Z-phenylhydrazone (4b) of 5-amino-3-benzoyl-1,2,4-oxadiazole into the
      relevant triazoles 5a and 5b in toluene has been quantitatively investigated in
      the presence of trichloroacetic acid (TCA) and of piperidine at 313.1 K. While
      the behavior in the presence of piperidine recalls the one previously evidenced
      for some Z-hydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole, the study of the
      reactivity in the presence of TCA has most interestingly evidenced a general-acid
      catalyzed rearrangement for "both" 4a and 4b. Thus, 4a offers the first example
      of a solvent-dependent dichotomic behavior in MRH processes on 1,2,4-oxadiazole
      derivatives as far as it undergoes an "acidic hydrolysis" in dioxane/water and a
      "rearrangement" in toluene.

PMID- 15575749
TI  - Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for
      alphaVbeta3 integrin antagonists.
AB  - The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a
      and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b,
      key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described.
      The syntheses rely on the efficient double Sonogashira reactions of 2,5
      dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines
      10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1
      amines 9a/9b.

PMID- 15575750
TI  - Electrochemical synthesis of dimerizing and nondimerizing orthoquinone
      monoketals.
AB  - Anodic oxidation of appropriately substituted 2-methoxyphenols or alpha-(2
      methoxyphenoxy)-2-methylpropionic acids in the presence of methanol furnishes
      stable orthoquinone monoketals, and thus constitutes a valuable alternative to
      the use of chemical oxidants that are often based on toxic metallic species. The
      propionic acid derivatives are initially converted into O-spirolactonic quinone
      bisketals that are then selectively hydrolyzed into the desired monoketal
      compounds. In the absence of blocking substituents, orthoquinone monoketals
      spontaneously undergo Diels-Alder dimerizations into tricyclododecadienedienones
      with extraordinary site selectivity, regioselectivity, and stereoselectivity.
      Suggestions are made to open up a new track for a long awaited rationalization of
      these controls on the basis of the intramolecular [2 + 2] reactivity of these
      orthoquinone monoketal-derived cyclodimers.

PMID- 15575751
TI  - Mild and selective reduction of imines: formation of an unsymmetrical macrocycle.
AB  - During investigations of 5, a [3 + 3] Schiff-base macrocycle with six imines, a
      partially reduced Schiff-base macrocycle, 6, possessing one CH(2)NH and five
      imine groups was obtained. Control experiments and deuterium labeling indicate
      that the macrocycle is reduced by a benzimidazoline generated during the
      reaction. Benzimidazolines may be convenient reagents for the mild and selective
      reduction of imines.

PMID- 15575752
TI  - A convenient and efficient route for the allylation of aromatic amines and alpha
      aryl aldehydes with alkynes in the presence of a Pd(0)/PhCOOH combined catalyst
      system.
AB  - The allylation of aromatic amines with alkynes proceeded smoothly in the presence
      of catalytic amounts of Pd(PPh(3))(4) and benzoic acid. The allylation products
      were obtained in high yields in a regio- and stereoselective manner. The effect
      of various groups on the nitrogen atom of anilines was studied. Regardless of the
      substituent (electron withdrawing or electron donating) on the aromatic ring, the
      reaction proceeded well. Various functionalities, including -CH(3), -OMe, -Cl, 
      CN, -COOMe, -NO(2) and -COCH(3) were tolerated under the reaction conditions.
      Similarly, the allylation of alpha-aryl aldehydes proceeded well with the same
      level of regio- and stereoselectivity as the allylation of aromatic amines. This
      reaction provides the second example of the transition metal catalyzed direct
      alpha-allylation of aldehydes.

PMID- 15575753
TI  - Second generation fluorous DEAD reagents have expanded scope in the Mitsunobu
      reaction and retain convenient separation features.
AB  - First generation fluorous DEAD reagent bis(perfluorohexylethyl)azo dicarboxylate
      (C(6)F(13)(CH(2))(2)O(2)CN=NCO(2)(CH(2))(2)C(6)F(13), F-DEAD-1) has been shown to
      underperform relative to diisopropylazodicarboxylate in difficult Mitsunobu
      reactions involving hindered alcohols or less acidic pronucleophiles (phenols).
      Two new second generation fluorous reagents bearing propylene spacers instead of
      the ethylene spacers show expanded reaction scope while retaining the easy
      fluorous separation features. Byproducts from "half fluorous" reagent
      perfluorooctylpropyl tert-butyl azo dicarboxylate
      (C(8)F(17)(CH(2))(3)O(2)CN=NCO2(t)Bu, F-DEAD-2) can be removed by fluorous flash
      chromatography, and byproducts from bis(perfluorohexylpropyl)azo dicarboxylate
      (C(6)F(13)(CH(2))(3)O(2)CN=NCO(2)(CH(2))(3)C(6)F(13), F-DEAD-3) can be removed by
      fluorous solid-phase extraction. The new reagents promise to provide general and
      complementary solutions for separation problems in Mitsunobu reactions without
      restricting reaction scope.

PMID- 15575754
TI  - Synthesis of novel Bi-, Tri-, and tetracyclic nucleosides by reaction of a common
      cyclic enamine derived from TSAO-T with nucleophiles.
AB  - We report here the efficient regio- and stereoselective synthesis of new
      polycyclic nucleosides using a common cyclic enamine (7) as the starting
      material. In fact, the reaction of 7, easily prepared by reaction of 5'-O-Tosyl
      TSAO-T under basic nonnucleophilic conditions (potassium carbonate), with
      different classes of nucleophiles, for example, nitrogen-, oxygen-, sulfur-, and
      carbon-based nucleophiles, or with amino acids afforded, with total regio- and
      stereoselectivity, new bi-, tri-, and tetracyclic nucleosides. This
      straighforward route represents an original and unambiguously regio- and
      stereoselective pathway to these compounds. Some of these polycyclic nucleosides
      may be useful intermediates for a second series of reactions that may lead to the
      generation of structurally new nucleosides.

PMID- 15575755
TI  - Preparation of fluoroalkyl imines, amines, enamines, ketones, alpha-amino
      carbonyls, and alpha-amino acids from primary enamine phosphonates.
AB  - A simple method for preparation of fluoroalkyl beta-enaminophosphonates 1 from
      alkylphosphonates 2 and perfluoroalkyl nitriles 3 is reported. Olefination
      reaction of functionalized phosphates 1 with aldehydes gives alpha,beta
      unsaturated imines 5. Acid hydrolysis of these fluoroalkyl derivatives 5 affords
      alpha,beta-unsaturated ketones 6, while their selective reduction with hydrides
      leads to the formation of allylamines 7, enamines 8, and saturated ketones 9 or
      amines 10. Selective oxidative cleavage of the carbon-carbon double bond of
      allylamines 7 gives fluorinated alpha-amino aldehydes 12, alpha-amino ketones 13,
      or alpha-amino acid derivatives 14.

PMID- 15575756
TI  - Stereoselective access to the versatile 4-aminohex-5-ene-1,2,3-triol pattern.
AB  - We developed a stereocontrolled route allowing potential access to the eight
      isomers of 4-benzylaminohex-5-ene-1,2,3-triol in two or four steps and ca. 50%
      yield from readily available chiral nonracemic cis- or trans-alpha,beta
      epoxyimine precursors. A new (NH(4))(2)CO(3)-based carboxylation/intramolecular
      cyclization sequence allowed regio- and stereocontrolled C-3 epoxide opening
      while neat C-2 hydrolysis was ensured by simple aqueous acidic treatment.

PMID- 15575757
TI  - One-pot synthesis of benzo[e]1,4-oxathiepin-5-ones under solvent-free condition
      via self-promoted thiolysis of 1,2-epoxides.
AB  - Under solvent-free conditions, thiosalicylic acid (2) efficiently self-promotes
      the thiolysis of 1,2-epoxides 1, anti-stereoselectively and generally totally
      beta-regioselectively. The resulting beta-hydroxysulfide products 3 have been
      obtained in very good yields. Benzo[e]1,4-oxathiepin-5-ones 4 have been easily
      prepared in a regio- and diasteroselective manner and in satisfactory yields
      under SFC by a one-pot protocol including nucleophilic ring opening of 1,2
      epoxides 1 by thiosalicylic acid (2) and thermally induced lactonization of beta
      hydroxy arylsulfides 3. Solvent-free condition and the absence of any catalyst
      make this procedure atom-economical and environmentally friendly.

PMID- 15575758
TI  - General method for the preparation of beta,beta-difluoroacrylates using BrF3.
AB  - Various esters were reacted with base, carbon disulfide, and methyl iodide,
      producing 2-carboalkoxy-1,1-bis(methyl sulfide)-1-alkenes (2). The reaction of 2
      with BrF(3), followed by oxidation with HOF.CH(3)CN gave the
      bromodifluorosulfonyl derivatives 5. Subsequent treatment with Raney nickel led
      to alpha-substituted beta,beta-difluoroacrylates 6 in overall yields of 50-80%.

PMID- 15575759
TI  - Asymmetric total syntheses of (+)-mycoepoxydiene and related natural product (-)
      1893A: application of one-pot ring-opening/cross/ring-closing metathesis to
      construct their 9-oxabicyclo[4.2.1]nona-2,4-diene skeleton.
AB  - The total syntheses of (+)-mycoepoxydiene and (-)-1893A have been completed. The
      present synthetic strategy features the use of one-pot ring-opening/cross
      metathesis (ROM/CM) followed by a ring-closing metathesis (RCM) reaction,
      allowing for the concise construction of the 9-oxabicyclo[4.2.1]nona-2,4-diene
      framework from a 7-oxabicyclo[2.2.1]hept-2-ene derivative and 1,3-butadiene. The
      sequential metathesis product was converted into (+)-mycoepoxydiene through the
      oxidative rearrangement of a furfuryl alcohol to a pyranone, thereby establishing
      its absolute stereochemistry. From the common intermediate, a structurally
      related natural product (-)-1893A was also synthesized via the vinylogous aldol
      reaction.

PMID- 15575760
TI  - Stereocontrolled syntheses of the nemorensic acids using 6-diazoheptane-2,5-dione
      in carbonyl ylide cycloadditions.
AB  - Levulinic acid-derived 6-diazoheptane-2,5-dione (9) serves as a common precursor
      in a formal synthesis of frontalin 19, and in syntheses of cis-nemorensic acid 1,
      4-hydroxy-cis-nemorensic acid 2, 3-hydroxy-cis-nemorensic acid 3, and nemorensic
      acid 4. The key step in these syntheses is the Rh(2)(OAc)(4)-catalyzed tandem
      carbonyl ylide formation-intermolecular 1,3-dipolar cycloadditions of diazodione
      9 with formaldehyde, alkynes or allene, which occur with high regioselectivity.
      Subsequent oxidative cleavage of the ring originally derived from the cyclic
      carbonyl ylide intermediate provides a straightforward access to polysubstituted
      tetrahydrofurans, and in particular an efficient entry to the nemorensic acids.
      Enantioselective cycloadditions with diazodione 9, using chiral rhodium
      catalysts, gave cycloadducts in up to 51% ee.

PMID- 15575761
TI  - Pseudoprolines as removable turn inducers: tools for the cyclization of small
      peptides.
AB  - The cyclization of small peptides which do not incorporate turn inducers is often
      difficult. We have developed a method involving the use of removable turn
      inducers, in the form of pseudoprolines, for the cyclization of difficult peptide
      sequences. The pseudoprolines induce a cisoid amide bond in the peptide backbone
      which facilitates cyclization. They are then readily removed to yield a cyclic
      peptide that does not contain any turn inducers.

PMID- 15575762
TI  - Total synthesis of ustiloxin D and considerations on the origin of selectivity of
      the asymmetric allylic alkylation.
AB  - As part of investigations into cell cycle checkpoint inhibitors, an asymmetric
      synthesis of the antimitotic natural product, ustiloxin D, has been completed. A
      salen-Al-catalyzed aldol reaction was employed to construct a chiral oxazoline 9
      (99% yield, 98% ee) that served the dual purpose of installing the necessary 1,2
      amino alcohol functionality as well as providing an efficient synthon for the
      requisite methylamino group at C9. The chiral aryl-alkyl ether was assembled
      using a Pd-catalyzed asymmetric allylic alkylation that notably delivered a
      product with stereochemistry opposite to that predicted by precedent. The linear
      tetrapeptide was subsequently cyclized to produce ustiloxin D. The mechanistic
      origin of the allylic alkylation selectivity was further investigated, and a
      working hypothesis for the origin of the observed stereoselectivity has been
      proposed.

PMID- 15575763
TI  - Et2AlCl-promoted asymmetric phenylseleno group transfer radical cyclization
      reactions of unsaturated beta-hydroxy esters.
AB  - We have developed a new method for asymmetric phenylseleno group transfer radical
      cyclization of unsaturated beta-hydroxy esters. Various unsaturated alpha
      phenylseleno beta-hydroxy esters underwent radical cyclization in the presence of
      Et(2)AlCl in benzene with sunlamp irradiation at 25-30 degrees C to give mono-
      and bicyclic group-transferred products in an efficient and highly regioselective
      and diastereoselective manner. To rationalize the high diastereoselectivities
      observed in this reaction, we propose a model based on chelation control of the
      aluminum alkoxides that are formed in situ. We devised a general method to
      prepare chiral radical precursors from which we obtained highly optically pure
      mono- and bicyclic group transfer products. The synthetic advantages of this
      method are demonstrated by our formal total synthesis of (-)-wilforonide. This
      paper presents the first examples of stereoselective group transfer radical
      cyclizations that occur via 1,2-asymmetric induction.

PMID- 15575764
TI  - N-H insertion reactions of primary ureas: the synthesis of highly substituted
      imidazolones and imidazoles from diazocarbonyls.
AB  - Primary ureas have been used as substrates in rhodium-catalyzed N-H insertion
      reactions with an array of diazocarbonyls. The insertion reaction is efficient
      and gives excellent selectivity and yields. The products from the insertion
      reaction with diazoketones cyclize readily in the presence of acid to yield the
      corresponding imidazolones that can be further derivatized by N-alkylation with
      alkyl, allyl, and benzyl halides. Alternatively, the imidazolones were treated
      with phosphorus oxybromide to form the corresponding 2-bromoimidazoles that were
      further functionalized using a Suzuki coupling reaction.

PMID- 15575765
TI  - Synthetic application of acylnitroso Diels-Alder derived aminocyclopentenols:
      total synthesis of (+)-streptazolin.
AB  - Concise total syntheses of (+)-streptazolin 1 and its more stable dihydro
      derivative 2 were accomplished via an intramolecular aldol condensation strategy
      starting from readily available aminocyclopentenol (-)-7. The synthetic sequence
      included reductive amination, stereoselective epoxidation, intramolecular aldol
      (and condensation) reaction, and Wittig reaction. The overall yield for dihydro
      derivative 2 from aminocyclopentenol (-)-7 was about 7% for a total of 14 steps.

PMID- 15575766
TI  - Synthesis of sapphyrins, heterosapphyrins, and carbasapphyrins by a "4 + 1"
      approach.
AB  - Sapphyrins are an important group of expanded porphyrins that show valuable anion
      binding characteristics. In this study, a "4 + 1" route to sapphyrin systems has
      been developed. Reaction of dialdehydes with a known tetrapyrrole intermediate
      11b incorporating a bipyrrolic subunit afforded a wide range of sapphyrin-type
      products. The best conditions for these reactions involved carrying out the
      condensation of the dialdehydes with the tetrapyrrole in TFA-dichloromethane,
      followed by oxidation with dilute aqueous solutions of ferric chloride. A pyrrole
      dialdehyde reacted under these conditions to give sapphyrin in 50% yield, while
      furan and thiophene dialdehydes afforded the corresponding oxa- and
      thiasapphyrins in 66-90% yield. Pyrrole dialdehydes with fused phenanthrene or
      acenaphthylene rings also reacted with 11b to give the related phenanthro- and
      acenaphthosapphyrins in excellent yields. As was the case for
      acenaphthoporphyrins, the acenaphthosapphyrin gave longer wavelength absorptions
      than the corresponding phenanthrene fused structure, although the differences
      were not as marked as those seen in the porphyrin series. Reaction of 11b with
      1,3-diformylindene gave a benzocarbasapphyrin in 38% yield, while a triformyl
      cyclopentadiene reacted with the tetrapyrrole to give a carbasapphyrin aldehyde
      in 7-12% yield. The free base carbasapphyrins were unstable but the
      monoprotonated hydrochloride salts could easily be isolated and characterized.
      Carbasapphyrins retain a strong diatropic ring current due to the presence of
      22pi electron delocalization pathways. In the presence of trifluoroacetic acid, C
      protonated dications are generated. Condensation of 1,3-azulenedicarbaldehyde
      with 11b gave an azulisapphyrin dihydrochloride salt in 35% yield, and this also
      showed a strong diatropic ring current. Addition of base gave the unstable free
      base form, while pyrrolidine formed an unstable adduct that showed an intense
      Soret band at 480 nm. These results demonstrate that many of the themes observed
      for modified porphyrins and carbaporphyrins also apply to the sapphyrin series,
      although in some cases reduced stability hampers these investigations.

PMID- 15575767
TI  - Synthesis, spectroscopy, and reactivity of meso-unsubstituted azuliporphyrins and
      their heteroanalogues. Oxidative ring contractions to carba-, oxacarba-,
      thiacarba-, and selenacarbaporphyrins.
AB  - This paper reports the first detailed study on meso-unsubstituted
      azuliporphyrins, an important family of porphyrin-like molecules where one of the
      usual pyrrole rings has been replaced by an azulene subunit. Although the azulene
      moiety introduces an element of cross-conjugation, zwitterionic resonance
      contributors with tropylium and carbaporphyrin substructures give azuliporphyrins
      diatropic character that falls midway between true carbaporphyrins and
      nonaromatic benziporphyrins. Protonation affords an aromatic dication where this
      type of resonance interaction is favored due to the associated charge
      delocalization. Two different "3 + 1" syntheses of meso-unsubstituted
      azuliporphyrins have been developed. Acid-catalyzed reaction of readily available
      tripyrrane dicarboxylic acids with 1,3-azulenedicarbaldehyde, followed by
      oxidation with DDQ or FeCl(3), affords good yields of azuliporphyrins.
      Alternatively, azulene reacted with acetoxymethylpyrroles (2 equiv) in refluxing
      acetic acid/2-propanol to give tripyrrane analogues, and following a deprotection
      step, condensation with a pyrrole dialdehyde in TFA-CH(2)Cl(2) gave the
      azuliporphyrin system. The latter approach was also used to prepare 23-thia- and
      23-selenaazuliporphyrins. However, reaction of the azulitripyrrane with 2,5
      furandicarbaldehyde produced a mixture of three oxacarbaporphyrins in moderate
      yield. The free base forms of thia- and selenaazuliporphyrins both showed
      intermediary aromatic character that was considerably enhanced upon protonation.
      The UV-vis spectra for azuliporphyrins and their heteroanalogues showed four
      bands between 350 and 500 nm and broad absorptions at higher wavelengths.
      Addition of TFA gave dications that showed porphyrin-like spectra with Soret
      bands between 460 and 500 nm. In the presence of pyrrolidine, azuliporphyrins and
      their heteroanalogues undergo nucleophilic attack on the seven-membered ring to
      give carbaporphyrin adducts. These systems also undergo oxidative rearrangements
      under basic conditions with t-BuOOH to give benzocarbaporphyrins. The
      selenaazuliporphyrin afforded two benzoselenacarbaporphyrins, a previously
      unknown core-modified carbaporphyrin system. The proton NMR spectra for these
      compounds showed strong diatropic ring currents with the internal CH resonance
      upfield above -5 ppm, while the meso-protons resonated downfield near 10 ppm. The
      UV-vis spectra were also porphyrin-like and gave strong Soret bands at ca. 440
      nm.

PMID- 15575768
TI  - A solvolysis model for 2-chloro-2-methyladamantane based on the linear solvation
      energy approach.
AB  - Solvolysis/dehydrohalogenation rates of 2-chloro-2-methyladamantane (CMA) in 15
      hydrogen-bond acidic and/or basic solvents are studied. The rates of reaction in
      these solvents have been correlated with the solvation equation developed by
      Kamlet, Abraham, and Taft. The linear solvation energy relationship (LSER)
      derived from this study is given by the following equation: log k = -5.409 +
      2.219 + 2.505alpha(1) - 1.823beta(1) where , alpha(1), and beta(1) are the
      solvation parameters that measure the solvent dipolarity/polarizability, hydrogen
      bond acidity (electrophilicity), and hydrogen-bond basicity (nucleophilicity). A
      high correlation coefficient (r = 0.996, SD = 0.191) was achieved. The cavity
      term, which includes the Hildebrand parameter for solvent cohesive energy
      density, delta(H), was not found to be statistically significant for this
      reaction substrate. The resulting equation allows calculated rates of reaction in
      other solvents and provides insight into the reaction pathway. In a previously
      reported correlation for another tertiary chloride, tert-butyl chloride (TBC),
      the coefficients for alpha(1) and are significantly larger and the coefficient
      for is statistically significant. In addition, the coefficient for beta(1) in the
      TBC correlation is positive, rather than negative, indicating that the transition
      states for TBC and CMA are significantly different. These results demonstrate why
      the uses of simple solvolytic correlation methods may be invalid even for
      comparisons of similar type substrates, e.g., tertiary chlorides. Also, these
      results provide confidence in the use of multiple linear regression analysis for
      predicting solvolytic rates in additional solvents.

PMID- 15575769
TI  - The role of aromatic radical cations and benzylic cations in the 2,4,6
      triphenylpyrylium tetrafluoroborate photosensitized oxidation of ring
      methoxylated benzyl alcohols in CH2Cl2 solution.
AB  - A steady-state and laser flash photolysis (LFP) study of the TPPBF(4)
      photosensitized oxidation of ring-methoxylated benzyl alcohols has been carried
      out. Direct evidence on the involvement of intermediate benzyl alcohol radical
      cations and benzylic cations in these reactions has been provided through LFP
      experiments. The reactions lead to the formation of products (benzaldehydes,
      dibenzyl ethers, and diphenylmethanes) whose amounts and distributions are
      influenced by the number and relative position of the methoxy substituents. This
      behavior has been rationalized in terms of the interplay between the stabilities
      of benzyl alcohol radical cations and benzyl cations involved in these processes.
      A general mechanism for the TPPBF(4)-photosensitized reactions of ring
      methoxylated benzyl alcohols has been proposed, where the alpha-OH group of the
      parent substrate acts as the deprotonating base promoting alpha-C-H deprotonation
      of the benzyl alcohol radical cation (formed after electron transfer from the
      benzyl alcohol to TPP) to give a benzyl radical and a protonated benzyl alcohol,
      precursor of the benzylic cation. This hypothesis is in contrast with previous
      studies, where formation of the benzyl cation was suggested to occur from the
      neutral benzyl alcohol through the Lewis acid action of excited TPP(+) (TPP).

PMID- 15575770
TI  - Synthesis of meso-arylsulfanyl- and alkylsulfanyl-substituted porphyrins via
      palladium-mediated C-S bond formation.
AB  - A family of new meso-arylsulfanyl- and alkylsulfanyl-substituted porphyrins were
      efficiently synthesized from direct reactions of meso-brominated porphyrins with
      thiols via palladium-mediated C-S bond formation. The catalytic method can be
      performed under mild conditions with both mono- and bis-substituted meso
      bromoporphyrins as well as their zinc complexes and is suitable for different
      types of thiols. With the use of selenols, meso-seleno-substituted porphyrins can
      also be prepared similarly.

PMID- 15575771
TI  - Palladium-mediated arylation of 3-aminopiperidines and 3-aminopyrrolidines.
AB  - This paper describes the palladium-catalyzed arylation of 1-substituted 3
      aminopyrrolidines or piperidines. Palladium(0) (1-2 mol %) in conjunction with
      "Buchwald's ligand" [2-(dimethylamino)-2'-(dicyclohexylphosphine)biphenyl] was
      shown to be the catalyst of choice for the coupling with aryl bromides or
      chlorides. When bromobenzene was used, a strong temperature effect was noticed.
      Whereas no reaction occurred at 100 degrees C, yields higher than 85% were
      obtained at 130 degrees C for each substrate. Such an effect was not observed
      when diphosphines were used. Whereas Xantphos and, to a lesser extent BINAP, were
      moderately efficient in the coupling of all diamines, the palladium-mediated
      arylation in the presence of monophosphines was strongly dependent on the
      substrate. The results suggest the participation of both nitrogens of the
      aminoheterocycle in the reactive intermediate. This participation could also
      account for the highly selective arylation of the endocyclic nitrogen of
      unsubstituted 3-aminopyrrolidine or piperidine. Optimal conditions were found for
      the arylation using 2- or 4-substituted electron-poor or enriched aryl halides.

PMID- 15575772
TI  - Regioselectivity in the addition of vinylmagnesium bromide to heteroarylic
      ketones: C- versus O-alkylation.
AB  - The reactivity of heteroarylic ketones toward vinylmagnesium bromide (2) and the
      regiochemistry of the addition were investigated. The reactivity drastically
      increases when the carbonyl is conjugated with at least one aza group and the
      regiochemistry of the addition of the vinyl Grignard reagent depends on the
      carbonyl compound: in the series of di(heteroazolyl) ketones the O-alkylation
      product was observed as unique with di(1,3-benzothiazol-2-yl) ketone, and in
      different relative ratios with respect to the classic C-alkylation product with
      di(1,3-thiazol-2-yl) ketone, (1,3-benzothiazol-2-yl) (1,3-thiazol-2-yl) ketone,
      and di(1,3-benzoxazol-2-yl) ketone, whereas di(N-methylbenzimidazol-2-yl) ketone
      gave the exclusive formation of the carbinol. This behavior can be explained by
      the intervention of the delocalization power of the heterocyclic ring and this
      was confirmed by the results obtained from the reaction between vinylmagnesium
      bromide and a series of mixed (1,3-benzothiazol-2-yl) (para-substituted phenyl)
      ketones, that showed a relative O-/C-alkylation ratio dependent on the nature and
      on the electronic effect of the substituent on the phenyl ring. The results are
      in agreement with the existence of intermediate species bearing a negative charge
      on the benzylic carbonyl carbon atom, and make the O-alkylation reaction between
      vinyl Grignard reagents and carbonyl compounds no longer a rare case, since it
      was observed with a number of heterocyclic carbonyl compounds, such as (1,3
      benzothiazol-2-yl) aryl ketones and di(heteroaryl) ketones of the pentatomic 1,3
      heteroazolic series.

PMID- 15575773
TI  - Synthesis and characterization of highly conjugated, chiral bridging ligands.
AB  - This paper describes the synthesis of four chiral derivatives of the
      electronically highly conjugated tetra-2-pyridylpyrazine (TPPZ) bridging ligand,
      which are denoted (R)- and (S)-4,5- and 5,6-pineno-tetra-2-pyridylpyrazine
      (PTPPZ). Preparation of these ligands was undertaken through the use of
      commercially available, enantiomerically pure (1R)- and (1S)-alpha-pinene, which
      was functionalized and subsequently employed in a Krohnke pyridine synthesis
      involving a furan-substituted pyridinium salt to yield a chiral, furan
      substituted pyridyl intermediate. Oxidative degradation and subsequent reduction
      of this furan led to a chiral, substituted 2-pyridylaldehyde, which underwent a
      pyridoin condensation followed by cyclization to produce the final PTPPZ ligands.

PMID- 15575774
TI  - Highly enantioselective reaction of alpha-selenoorganolithium compounds with
      chiral bis(oxazoline)s and preparation of enantioenriched benzylidencyclohexanes.
AB  - The enantioselective reaction of alpha-seleno carbanions derived from
      bis(phenylseleno)acetal and bis(2-pyridylseleno)acetal in the presence of
      bis(oxazoline)s with various electrophiles gave products with high
      enantioselectivity. The enantioselective reaction of alpha-lithio benzyl 2
      pyridyl selenide gave the products with stereochemistry reverse to that obtained
      in the reaction of alpha-lithio benzyl phenyl selenide. Mechanistic investigation
      suggests the enantiodetermination of these reactions at -78 degrees C depends on
      dynamic thermodynamic resolution. The enantioselective reaction was applied to
      the preparation of enantioenriched olefins and epoxide.

PMID- 15575775
TI  - 7-trifluoromethylquinoline-functionalized luminescent photochromic spiropyran
      with the stable merocyanine species both in solution and in the solid state.
AB  - A new spiropyran (SP2) with the stable merocyanine form (MC2) both in solution
      and in the solid state at room temperature was designed and synthesized. The
      stability of MC2 is believed to be due to the electron-withdrawing effect of both
      the quinoline and the trifluoromethyl groups. (1)H NMR spectra indicate that the
      ratio of the open form vs the closed form of SP2 is dependent on the polarity of
      solvents. Single crystals composed of only the open form (MC2) were successfully
      obtained. X-ray structural analysis indicates that except trifluoromethyl and two
      methyl groups MC2 is completely planar with an s-trans,s-cis conformation. It
      should be noted that this is the first report of the X-ray crystal structure of
      the pure open form of spiropyran. MC2 can be slowly transformed into SP2 at -30
      degrees C or lower temperature, and the process is accelerated by visible light
      irradiation. This special photochromic behavior can be explained by the
      calculated thermodynamic data. The spectral properties of SP2/MC2 in the presence
      of different metal ions are also studied, and the results show the potential
      application of SP2/MC2 in sensing metal ions.

PMID- 15575776
TI  - Highly efficient chemoselective deprotection of O,O-acetals and O,O-ketals
      catalyzed by molecular iodine in acetone.
AB  - An extremely convenient method for deprotection of acetals and ketals catalyzed
      by molecular iodine (10 mol %) in acetone is reported. The protocol achieved the
      deprotection of acyclic or cyclic O,O-acetals and O,O-ketals in excellent yields
      within a few minutes under neutral conditions. The double bond, hydroxyl group,
      and acetate group remained unchanged, and the highly acid-sensitive furyl, tert
      butyl ethers, and ketone-oxime stayed intact under these conditions.

PMID- 15575777
TI  - Novel domino reactions for diterpene synthesis.
AB  - New types of concerted domino acylation-cycloalkylation/alkylation-cycloacylation
      reactions have been described. These processes promoted by methanesulfonic acid
      phosphorus pentoxide and concentrated H(2)SO(4), respectively, provide efficient,
      elegant, and expeditious routes for biologically active naturally occurring
      diterpenoids, namely (+/-)-ferruginol (1), (+/-)-nimbidiol (2), (+/-)-nimbiol
      (3), (+/-)-totarol (4), and ar-abietatriene (5).

PMID- 15575778
TI  - Synthesis of 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene using alkyneselenolate.
AB  - The reaction of lithium alkyneselenolate with alpha,beta-unsaturated ketone and
      then alkyl or acyl halide afforded 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene.
      The structure of the cyclobutene was elucidated by IR, MS, (1)H, (13)C, and
      (77)Se NMR, COSY, HMQC, and HMBC data and X-ray analysis.

PMID- 15575779
TI  - Synthesis of nitrogen-functionalized beta-cycloaltrins.
AB  - We report the synthesis of functionalized beta-cycloaltrins having azido groups
      at C-3, C-6, and both C-3 and C-6 by nucleophilic epoxy ring-opening of per-2,3
      anhidro-beta-cyclomannin derivatives. The value of these compounds as templates
      for further functionalization is exemplified by the conversion of heptakis(3,6
      diazido-3,6-dideoxy)-beta-cycloaltrin into the per-3,6-diamino, per-3,6
      diacetamido, per-3,6-dichloroacetamido, and per[3,6-bis(N'-ethylureido)]
      derivatives in good yields.

PMID- 15575780
TI  - An efficient RCM-based synthesis of orthogonally protected meso-DAP and FK565.
AB  - A condensation--ring-close--ring-open sequence was employed for the synthesis of
      orthogonally protected meso-2,6-diaminopimelic acid, starting from easily
      accessible chiral synthons. Condensation of suitably protected L-allylglycine and
      D-vinylglycinol derivatives was followed by Grubbs' ring-closing metathesis to
      generate the key lactam intermediate. This strategy has been applied to a concise
      total synthesis of the potent immunostimulatory peptide FK565.

PMID- 15575781
TI  - Novel ene trimerization of 1-phenylcyclopropene.
AB  - 1-Phenylcyclopropene (1) was synthesized by treatment of 1,1,2-tribromo-2
      phenylcyclopropane (2) with 2.5 equiv of methyllithium followed by protonation.
      Compound 1 underwent ene dimerization to form ene dimer 5 followed by ene
      reaction with monomer 1 (enophile) to give an ene trimer 6. Both of these two ene
      reactions derived endo transition states. In the meantime, the [2+2] adduct,
      trans-1,2-diphenylbicyclo[3.1.0.0(2,4)]hexane (7), was also formed. When the
      adduct 7 was heated at THF refluxing temperature, 1,2-diphenylcyclohexa-1,4-diene
      (8) was obtained. Compound 8 was treated with DDQ to yield o-diphenylbenzene.

PMID- 15575782
TI  - A novel biomimetic route to the 3-acyl-5-hydroxy-3-pyrrolin-2-one and 3-acyl-3,4
      epoxy-5-hydroxypyrrolidin-2-one ring systems.
AB  - Modified Moffat oxidation of alcohols 17, 22, and 25 afforded aldehydes that
      underwent intramolecular aldol reactions on treatment with a NaOH solution to
      yield 4-pyrrolin-2-ones 16, 23, and 26. Oxidation with DMDO at -40 degrees C
      provided 3-acyl-5-hydroxy-3-pyrrolin-2-ones 18, 24, and 27 with the ring system
      of oteromycin (3), UCS1025A (5), and related natural products. Further oxidation
      of 18 yielded 3-acyl-3,4-epoxy-5-hydroxy-pyrrolidin-2-one 19 with the ring system
      of fusarin C (1) and epolactaene (2). Dehydration of 18 afforded 20 with the
      talaroconvolutin A (4) ring system.

PMID- 15575783
TI  - Acetoxyl group directed cyclization promoted by SmI2: directing group determined
      stereocomplementarity.
AB  - Complete reversal of diastereoselectivity was observed in the SmI(2)-promoted
      ketyl-olefin coupling cyclizations of the hydroxy ketone or aldehyde and its
      acetate. For example, the stereodivergent synthesis of the epimeric five-membered
      ring alcohols 2 and 4 has been accomplished through the SmI(2)-induced ketyl
      olefin coupling cyclizations of the delta-hydroxy ketone 1 and delta-acetoxy
      ketone 3.

PMID- 15575784
TI  - A simple and efficient highly enantioselective synthesis of alpha-ionone and
      alpha-damascone.
AB  - An efficient highly enantioselective (ee > or =99%) synthesis of alpha-ionone and
      alpha-damascone is described. Both enantiomers of title compounds were
      synthesized through two straightforward pathways diverging from enantiopure (R)-
      or (S)-alpha-cyclogeraniol. These versatile building blocks were obtained by
      regioselective ZrCl(4)-promoted biomimetic cyclization of (6S)- or (6R)-(Z)-6,7
      epoxygeraniol, respectively, followed by deoxygenation of the so formed secondary
      alcohol. The chiral information was encoded by a highly regioselecive Sharpless
      asymmetric dihydroxylation of inexpensive geranyl acetate.

PMID- 15575785
TI  - Reactivity of phthalimide N-oxyl radical (PINO) toward the phenolic O-H bond. A
      kinetic study.
AB  - The reactivity of the phthalimide N-oxyl radical (PINO) toward the OH bond of a
      series of substituted phenols was kinetically investigated in CH(3)CN. The
      reaction selectivity and the deuterium kinetic isotope effect were determined.
      Information on the kinetic solvent effect was also obtained with phenol as the
      substrate.

PMID- 15575786
TI  - Efficient synthesis of alkynylsilyl ethers and silaketals via base-induced
      alkynylsilane alcoholysis.
AB  - The efficient silylation of alcohols with di- and trialkynylsilanes was achieved
      under base-catalyzed conditions to afford alkynyl silyl ethers and symmetrical
      alkynyl silaketals in good yield. A selective alcoholysis of dialkynyl silyl
      ethers to mixed silaketals was also demonstrated. These products served as
      substrates for enyne ring-closing metathesis and, consequently, as precursors to
      stereochemically defined 1,3-dienes.

PMID- 15575787
TI  - Vinyldimethylphenylsilanes as safety catch silanols in fluoride-free palladium
      catalyzed cross-coupling reactions.
AB  - A series of five structurally diverse vinyldimethylphenylsilanes have been shown
      to undergo a fluoride-free one-pot palladium-catalyzed cross-coupling reaction
      with phenyl iodide to give ipso coupled products in 62-86% yield. The limitations
      of this present protocol lie in the activation of Si-Ph vs protodesilylation by
      KOTMS/18-C-6, which seems sensitive to the sterics of cis substituents, but not
      geminal substituents.

PMID- 15575788
TI  - Iron tricarbonyl stabilized pentadienyl cation as initiator for cascade
      polycyclizations: a diastereoselective entry into octahydrophenanthrenes.
AB  - A new example is provided of completely diastereoselective polycyclization,
      affording the octahydrophenanthrene framework. Generation of an iron tricarbonyl
      stabilized pentadienyl carbocation is the triggering event of the cascade
      reaction. The carbocation is generated by anchimerically assisted regiospecific
      protonation of a double bond adjacent to the iron tricarbonyl diene moiety.
      Tetrafluoroboric acid ether complex appears to be the optimum reagent, affording
      good yields, even under catalytic conditions.

PMID- 15575789
TI  - Selenium-catalyzed halolactonization: nucleophilic activation of electrophilic
      halogenating reagents.
AB  - Diphenyl diselenide catalyzes the halolactonization of unsaturated acids with N
      halosuccinimides under mild conditions. The diselenide not only accelerates the
      reactions, but in some cases affords regiocontrol in favor of gamma-lactone
      products. Experiments show that the regioselectivity in favor of gamma-lactones
      is a result of kinetic rather than thermodynamic control.

PMID- 15575790
TI  - Expedient total syntheses of rhein and diacerhein via Fries rearrangement.
AB  - Short and practical total syntheses of rhein (1) and diacerhein (2) have been
      achieved via a Fries rearrangement and bis-carbonylation strategy followed by
      cyclization in molten salt, starting from dibromoester 7.

PMID- 15575791
TI  - A convenient method for the conversion of hindered carboxylic acids to N-methoxy
      N-methyl (Weinreb) amides.
AB  - The conversion of sterically hindered carboxylic acids to N-methoxy-N-methyl
      amides can be efficiently carried out with 1.1 equiv of methanesulfonyl chloride,
      3 equiv of triethylamine, and 1.1 equiv of N-methoxy-N-methylamine. Yields for
      this process range from 59% to 88%. The major byproduct in these reactions, N
      methoxy-N-methylmethanesulfonamide, can be removed by placing the product mixture
      under vacuum for 14-24 h.

PMID- 15575793
TI  - Severe Acute Respiratory Syndrome and sport: facts and fallacies.
AB  - Severe Acute Respiratory Syndrome (SARS) not only paralysed economic activities
      in SARS-affected cities, it also affected sporting activities. SARS was
      identified in Hong Kong in late February 2003 and the WHO issued a global alert
      on 12 March, 2003. The incubation period of SARS is usually 4-6 days and patients
      commonly present with high fever (temperature >38 degrees C), dry cough, chills
      and rigor, dyspnoea and diarrhoea. Although a specific antiviral agent and
      vaccines for SARS are not available at the time of writing, a standard treatment
      protocol for SARS has been developed. The average mortality rate is about 16% in
      Hong Kong.The coronavirus is a common pathogen for upper respiratory tract
      infection and is the most probable pathogen for SARS. Transmission methods may,
      therefore, be similar for both these infections. Transmission is possible when
      aerosolised viral particles come into contact with the susceptible host's mucous
      membrane, most commonly the nose, but also the mouth and eyes. With appropriate
      preventive measures to avoid contact with virus, the probability of infection is
      minimal. Isolation of those who have had close contact with confirmed or
      suspected SARS patients and/or who have persistent fever will be the most
      effective and practical method of avoiding contact. Maintaining personal hygiene
      and frequent hand washing can also reduce the risk of infection. Using diluted
      bleach (1 part bleach in 99 parts water) to cleanse training areas and equipment
      is also recommended. With proper event planning to conform with quarantine
      measures, special travel arrangements, facility sterilisation and use of venues
      with good ventilation and filtering systems, sport competition can still proceed.

PMID- 15575794
TI  - Single-subject research designs and data analyses for assessing elite athletes'
      conditioning.
AB  - Research in conditioning (all the processes of preparation for competition) has
      used group research designs, where multiple athletes are observed at one or more
      points in time. However, empirical reports of large inter-individual differences
      in response to conditioning regimens suggest that applied conditioning research
      would greatly benefit from single-subject research designs. Single-subject
      research designs allow us to find out the extent to which a specific conditioning
      regimen works for a specific athlete, as opposed to the average athlete, who is
      the focal point of group research designs. The aim of the following review is to
      outline the strategies and procedures of single-subject research as they pertain
      to the assessment of conditioning for individual athletes. The four main
      experimental designs in single-subject research are: the AB design, reversal
      (withdrawal) designs and their extensions, multiple baseline designs and
      alternating treatment designs. Visual and statistical analyses commonly used to
      analyse single-subject data, and advantages and limitations are discussed.
      Modelling of multivariate single-subject data using techniques such as dynamic
      factor analysis and structural equation modelling may identify individualised
      models of conditioning leading to better prediction of performance. Despite
      problems associated with data analyses in single-subject research (e.g. serial
      dependency), sports scientists should use single-subject research designs in
      applied conditioning research to understand how well an intervention (e.g. a
      training method) works and to predict performance for a particular athlete.

PMID- 15575795
TI  - Effects of exercise on the fatty-acid composition of blood and tissue lipids.
AB  - This article reviews the effects of acute and chronic exercise on the fatty-acid
      composition of animal and human tissues (plasma, skeletal muscle, heart, adipose
      tissue, liver, artery and erythrocytes), as reported in 68 studies spanning four
      decades. The most consistently observed effect has been an increase in the
      relative amount of unsaturated, especially monounsaturated, non-esterified fatty
      acids in plasma of both animals and humans after acute exercise. Chronic exercise
      seems to increase the proportion of polyunsaturated fatty acids and omega6 fatty
      acids, while decreasing the proportion of monounsaturated fatty acids in animal
      and human adipose tissue. Additionally, chronic exercise seems to decrease the
      relative amount of unsaturated fatty acids in liver lipids of animals and humans.
      There is no consensus regarding the effect of exercise on the fatty-acid
      composition of lipids in any other tissue. In general, the effects of exercise
      are independent of nutrition and, regarding skeletal muscle, muscle fibre type.
      The available literature shows that, in addition to modifying the concentrations
      of animal and human tissue lipids, exercise also changes their fatty-acid
      profile. Unfortunately, the available studies are so much divided among exercise
      models, species and biological samples that a cohesive picture of the plasticity
      of the fatty-acid pattern of most tissues toward exercise has not emerged. Future
      studies should focus on determining the fatty-acid profile of separate lipid
      classes (rather than total lipids) in separate subcellular fractions (rather than
      whole tissues), examining tissues and organs on which no data are available and
      exploring the mechanisms of the exercise-induced changes in fatty-acid
      composition.

PMID- 15575797
TI  - The neurotransmitters of sleep.
AB  - The part of the brain most important in regulating sleep duration is the
      hypothalamus. Certain groups of hypothalamic neurons and adjacent groups of basal
      forebrain neurons produce the neurotransmitter gamma-aminobutyric acid (GABA).
      Projections of these GABA neurons inhibit the firing of cells involved in
      wakefulness. Several groups of neurons have been shown to be inhibited by this
      action--including neurons containing histamine, norepinephrine, serotonin,
      hypocretin, and glutamate--and this inhibition promotes sleep. Hypocretin (also
      called orexin) was discovered in 1998, and its role in sleep and narcolepsy was
      identified in 2001. Other as-yet undiscovered transmitters are undoubtedly
      involved in sleep control. The transmitters discussed in this article have been
      the most thoroughly studied, and many aspects of the role of each of these
      transmitters in relation to sleep are reasonably well understood.

PMID- 15575796
TI  - Exercise and multiple sclerosis.
AB  - The pathophysiology of multiple sclerosis (MS) is characterised by fatigue, motor
      weakness, spasticity, poor balance, heat sensitivity and mental depression. Also,
      MS symptoms may lead to physical inactivity associated with the development of
      secondary diseases. Persons with MS are thus challenged by their disability when
      attempting to pursue an active lifestyle compatible with health-related fitness.
      Although exercise prescription is gaining favour as a therapeutic strategy to
      minimise the loss of functional capacity in chronic diseases, it remains under
      utilised as an intervention strategy in the MS population. However, a growing
      number of studies indicate that exercise in patients with mild-to-moderate MS
      provides similar fitness and psychological benefits as it does in healthy
      controls. We reviewed numerous studies describing the responses of selected MS
      patients to acute and chronic exercise compared with healthy controls. All
      training studies reported positive outcomes that outweighed potential adverse
      effects of the exercise intervention. Based on our review, this article
      highlights the role of exercise prescription in the multidisciplinary approach to
      MS disease management for improving and maintaining functional capacity. Despite
      the often unpredictable clinical course of MS, exercise programmes designed to
      increase cardiorespiratory fitness, muscle strength and mobility provide benefits
      that enhance lifestyle activity and quality of life while reducing risk of
      secondary disorders. Recommendations for the evaluation of cardiorespiratory
      fitness, muscle performance and flexibility are presented as well as basic
      guidelines for individualised exercise testing and training in MS. Special
      considerations for exercise, including medical management concerns, programme
      modifications and supervision, in the MS population are discussed.

PMID- 15575798
TI  - Characteristics and determinants of normal sleep.
AB  - Although sleep appears to simply be a body and mind at rest, it is actually a
      dynamic and complex physiologic state that is necessary for survival. Normal
      sleep is characterized by behavioral and physiologic changes as well as 2
      distinct sleep states, rapid eye movement (REM) and non-REM (NREM). Throughout
      the course of a night, people cycle between NREM and REM sleep via an ultradian
      rhythm, with most of sleep spent in NREM. Determinants involved in the regulation
      of sleep are the homeostatic and circadian processes. Despite being highly
      regulated, sleep is fragile, and its stages and duration may be affected by
      multiple factors, such as age, drugs, temperature, and medical and psychiatric
      disease. Variations in nighttime sleep impact subsequent sleep periods as well as
      daytime function.

PMID- 15575799
TI  - Epidemiology of daytime sleepiness: definitions, symptomatology, and prevalence.
AB  - Daytime sleepiness, or difficulty in maintaining a desired level of wakefulness,
      is frequently viewed by the general population as a common experience and
      predictable consequence of insufficient sleep. However, daytime sleepiness can
      have a serious impact on an individual's health, safety, and quality of life.
      Despite the fact that population-based studies have found that 1 in 5 adults
      suffers from daytime sleepiness, there is a lack of consistency in how daytime
      sleepiness is defined, measured, and interpreted, which may affect the medical
      management of the disorder. For example, many measures of sleepiness based on
      sleep propensity and falling asleep tend to overlook patients with insomnia and
      sleepiness. Sleep scales that contain sensitive and specific questions are needed
      to measure fatigue and perceptions of sleepiness.

PMID- 15575800
TI  - Assessment of excessive sleepiness and insomnia as they relate to circadian
      rhythm sleep disorders.
AB  - Sleep disturbances are associated with a number of psychiatric disorders,
      including depression, anxiety disorders, and substance use disorders, and many
      psychiatric patients report symptoms such as insomnia, tiredness, fatigue, and
      excessive sleepiness. Despite their known negative impact on daytime functioning
      and quality of life, less than 10% of individuals with these symptoms visit
      physicians specifically for their sleeping problems. Although there are many
      explanations for this lack of reporting, one possibility is that individuals are
      often unaware of the impact of sleepiness on their daytime functioning.
      Therefore, the burden of identifying sleepiness and its consequences often
      resides with physicians and other health care professionals. This process of
      detection is assisted by rating scales and subjective and objective tests.
      Although prior discussions on these topics have focused on the understanding and
      identification of either excessive sleepiness or insomnia, these symptoms often
      coexist, introducing a clinical challenge in that it becomes unclear which of
      these two should become the initial focus of clinical attention. When both
      excessive sleepiness and insomnia coexist, a circadian rhythm sleep disorder may
      be present, such as jet lag type, delayed and advanced sleep phase types, and
      shift work type.

PMID- 15575801
TI  - Recognizing sleep disorders in a primary care setting.
AB  - As many as one third of the general population suffers from some form of sleep
      disorder. Although sleep disorders are widespread in society, few patients
      present with overt sleep complaints; they instead present with symptoms of
      fatigue, excessive sleepiness, and impaired waking function. Untreated sleep
      disorders, particularly insomnia, can lead to potentially life-threatening
      automobile crashes and industrial accidents. In addition, poor motor, mental, and
      cognitive function at home, work, and school can negatively impact a patient's
      quality of life. Therefore, physicians must maintain a high index of suspicion
      for sleep disorders whenever they see patients, and they must ask sleep-related
      questions during office visits for acute conditions, chronic conditions, and
      annual physical examinations. Today's "24/7" society experiences sleep disorders
      in ever-increasing numbers, and people who work shifts are at risk for developing
      circadian rhythm sleep disorder, particularly shift work sleep disorder.
      Physicians must engage their patients in a discussion of their occupations and
      sleeping habits in order to detect and treat sleep disorders.

PMID- 15575802
TI  - Daytime sleepiness and insomnia as correlates of depression.
AB  - Insomnia and daytime sleepiness are often associated with depression. The
      possible relationships between sleep difficulties and depression are numerous.
      Insomnia and other sleep disturbances can be precursors to the onset of major
      depressive disorder, so they may act as risk factors for or predictors of
      depression. The symptomatology of depression also prominently includes insomnia,
      and sleep disturbances may be residual symptoms after response to antidepressant
      treatment. Insomnia and the resultant daytime sleepiness may be short-term or
      long-term side effects of antidepressant treatment as well. Whether insomnia is a
      precursor, symptom, residual symptom, or side effect of depression or its
      treatment, clinicians must give serious attention to and attempt to resolve sleep
      disturbances because of the risk of depression onset, worsening of depressive
      symptoms, and relapse of depression after response to antidepressant treatment.
      Remission of depression cannot be fully achieved until the associated insomnia
      and daytime sleepiness are resolved. This article describes the relationships
      between insomnia and depression and discusses the effects of various
      antidepressants on sleep. Finally, several different treatment options, including
      antidepressant monotherapy and augmentation of antidepressants with other
      medications, are explored.

PMID- 15575803
TI  - Cognitive-behavioral approaches to the treatment of insomnia.
AB  - Insomnia is a pervasive condition with various causes, manifestations, and health
      consequences. Regardless of the initial cause or event that precipitates
      insomnia, it is perpetuated into a chronic condition through learned behaviors
      and cognitions that foster sleeplessness. This article reviews the rationale and
      objectives of cognitive-behavioral therapy (CBT), a safe and effective treatment
      for insomnia that may be used to augment hypnotic drugs or as a monotherapy.
      Cognitive-behavioral management of insomnia includes 3 components--behavioral,
      cognitive, and educational modules--and is usually presented in a group or
      individual therapy setting. Each treatment procedure is detailed herein, and
      recommendations for implementation are given. The evidence supporting this
      behavioral approach shows that CBT is effective for 70% to 80% of patients and
      that it can significantly reduce several measures of insomnia, including sleep
      onset latency and wake-after-sleep onset. Aside from the clinically measurable
      changes, this therapy system enables many patients to regain a feeling of control
      over their sleep, thereby reducing the emotional distress that sleep disturbances
      cause. Some clinical and practical issues that often arise when implementing this
      therapeutic approach for insomnia are also discussed.

PMID- 15575804
TI  - Pharmacologic management of insomnia.
AB  - Pharmacotherapy is indicated for many types of insomnia, most notably transient
      insomnia associated with stress, acute illness, or jet lag. Many patients with
      chronic insomnia, including primary insomnia and insomnia secondary to a variety
      of medical and psychiatric disorders, also benefit from pharmacotherapy.
      Relatively few individuals receive prescription medication to help them sleep,
      and the majority use medication for a few nights to several weeks, as opposed to
      continuous use for months or years. The hypnotics available on the U.S. market
      today are benzodiazepine receptor agonists (BZRAs). The BZRAs are efficacious in
      reducing sleep latency, increasing total sleep time, reducing awakenings, and
      improving sleep quality without the development of tolerance in studies as long
      as 6 months. Side effects of the BZRAs are infrequent, dose-related, and related
      to the sedative properties of the drug. Sedating antidepressants are also
      frequently prescribed to promote sleep despite inadequate data to support their
      efficacy for this indication and a greater potential for clinically troublesome
      side effects.

PMID- 15575806
TI  - What did we do before computers?

PMID- 15575805
TI  - Pharmacologic management of daytime sleepiness.
AB  - Excessive daytime sleepiness and abnormal sleep-wake patterns are becoming
      increasingly pervasive in modern society. The major causes of excessive daytime
      sleepiness include pathologic abnormalities of the central nervous system, such
      as narcolepsy and idiopathic hypersomnia; deficiencies in quality or quantity of
      sleep, such as those caused by sleep apnea and poor sleep hygiene; disturbances
      to the body's natural circadian rhythm, such as those caused by shift work or jet
      lag; and drugs, which can increase sleepiness either therapeutically or as a side
      effect. Determining the cause of daytime sleepiness is the first step in treating
      it. Setting appropriate and realistic treatment goals with the patient and
      initiating treatment are the next steps. Although the medications available to
      improve daytime wakefulness (e.g., amphetamines, methylphenidate, pemoline, and
      modafinil) are effective, they are not a substitute for sleep. Finally, timely
      follow-up is necessary to monitor treatment adherence, response, and side
      effects.

PMID- 15575807
TI  - alpha crystallin: hot molecule, not just a lens packer.

PMID- 15575808
TI  - alpha-crystallin: a review of its structure and function.
AB  - alpha-crystallin, the major protein of the mammalian lens in most species, is an
      aggregate assembled from two polypeptides, each with a molecular weight around
      20,000 Da. It is polydisperse and can be isolated in a variety of forms,
      including spherical particles with molecular weights ranging upwards from about
      200 kDa. Sequence comparisons reveal that it is a member of the small heat shock
      protein (shsp) family. These proteins are aggregates assembled from polypeptides
      of 10 to 25 kDa that share a common central domain of about 90 residues (the
      'alpha-crystallin domain') with variable N- and C-terminal extensions. alpha
      crystallin has been intensively studied for more than 50 years but its three
      dimensional structure remains unknown because it has not been possible to obtain
      crystals for X-ray studies and it is too large for NMR measurements. Structural
      information has been derived from a variety of solution studies. Because of the
      protein's polydispersity, interpretation of data has been difficult. This led to
      different viewpoints and vigorous debate on its structure and properties.
      Recently, the crystal structures of two closely-related small heat shock proteins
      have been determined. These have provided some insight into the structure of a
      crystallin and explanations of previous observations. Like many other heat shock
      proteins, alpha-crystallin exhibits chaperone-like properties, including the
      ability to prevent the precipitation of denatured proteins and to increase
      cellular tolerance to stress. It has been suggested that these functions are
      important for the maintenance of lens transparency and the prevention of
      cataract.

PMID- 15575809
TI  - The influence of lens conditioning on signs and symptoms with new hydrogel
      contact lenses.
AB  - BACKGROUND: Daily disposable contact lenses are considered to be the pinnacle of
      safe contact lens wear, yet it has been suggested that it takes some period of
      wear for the lens surface to reach optimal compatibility with the ocular surface.
      This study assesses the influence of brief treatment with a conditioning drop on
      the ocular response to new contact lenses over a single day of wear. METHODS: The
      study was a single-masked, paired (contralateral) comparison of the signs and
      symptoms with wear of new Acuvue 2 contact lenses pretreated with a conditioning
      agent containing carboxymethylcellulose (carmellose, CMC) against new lenses
      inserted directly from the blister pack. Sixty-one subjects participated in the
      study, of whom 59 were considered eligible for data analysis. Subjects were also
      divided into symptomatic and asymptomatic lens wearers based on their overall
      comfort level in lens wear. Symptoms and signs were recorded at lens delivery and
      following eight hours of wear. RESULTS: A set of slitlamp signs, comprising
      corneal staining (p <0.05), limbal redness (p <0.05), bulbar conjunctival
      hyperaemia (p <0.05), bulbar conjunctival staining (p <0.01) and palpebral
      conjunctival redness (p <0.05) showed small but statistically significant (p
      <0.05) end-of-day mean values in favour of the lens that was conditioned with the
      rewetting agent. These data were supported by the proportion of subjects showing
      lower gradings with conditioned lenses versus unconditioned lenses, as follows:
      corneal staining (35 per cent versus 12 per cent, p <0.05), limbal redness (43
      per cent versus 22 per cent, p <0.05), bulbar conjunctival hyperaemia (50 per
      cent versus 15 per cent, p <0.05), bulbar conjunctival staining (46 per cent
      versus 30 per cent, p <0.1) and palpebral conjunctival hyperaemia (28 per cent
      versus 17 per cent, NS). For those subjects reporting symptoms with lens wear
      (n=12), there was a statistically significant (p <0.05) preference in terms of
      comfort as a result of preconditioning. CONCLUSIONS: The results of the
      investigation suggest that use of a conditioning agent can provide a more
      physiologically suitable environment for a new lens, thereby reducing the
      clinical signs associated with lens discomfort. The protocol used here, which is
      based on a statistical paradigm using standard pictorial grading scales, allows
      high sensitivity in detecting small changes in ocular parameters.

PMID- 15575810
TI  - Thermal cataract, from furnaces to lasers.
AB  - BACKGROUND: Thermal cataract has long been known as an occupational disease in
      furnace workers. This affliction has virtually disappeared in western countries
      due to improved working conditions. However, new light sources have appeared on
      the scene, in particular lasers, which might also be capable of producing thermal
      cataract. The aim of this survey is to review the history and describe the
      present state of knowledge. METHODS: Experimental work, mainly on rabbits, was
      reviewed and complemented with the results of calculations on the thermal changes
      in the ocular media. RESULTS: Safe exposure limits were derived over the optical
      spectrum from the near ultraviolet to the far infrared. CONCLUSIONS: Lasers may
      be a cause of thermal cataract only in the near ultraviolet. Moreover, in this
      field of research too, it is concluded that science may be regarded as the
      present state of misunderstanding.

PMID- 15575811
TI  - Heterogeneity in the ultrastructure of the mucous (goblet) cells of the rabbit
      palpebral conjunctiva.
AB  - AIM: The purpose of this study was to assess objectively the ultrastructure of
      the secretory granules in rabbit conjunctival mucin-producing 'goblet' cells.
      METHOD: The upper eyelids from five young adult dioestrous female rabbits were
      dissected out, stretched onto a cardboard support and prepared for transmission
      electron microscopy by repeated application of an isotonic two per cent
      glutaraldehyde fixative at room temperature. Post-fixation treatment included
      osmium tetroxide and staining with uranyl acetate and lead citrate. Low
      magnification micrographs were taken of the goblet cells of the conjunctiva,
      printed at a magnification of approximately 6,000 and the number, size and
      features of the secretory granules assessed. RESULTS: Across the entire palpebral
      conjunctiva of all five rabbits, the majority of mucous cells displayed a goblet
      shape and the secretory granules were uniformly pale in staining. The average
      width of the goblet cells was 10.8 +/- 1.1 microm and the diameter of the
      secretory granules was 0.82 +/- 0.16 microm. However, in localised regions across
      the palpebral conjunctiva of two of the rabbits, some goblet cells were different
      in that the secretory granules had either a denser-staining core, in which some
      of the granules were densely staining (while others were pale) or most of the
      granules were densely staining. These mucous cells had an average diameter of
      10.3 +/- 1.7 microm and the granule diameters averaged 0.88 +/- 0.01 microm. For
      these abnormal goblet cells, inflammatory cells were found in their immediate
      vicinity. Occasionally, goblet cells were seen to be in the process of
      degranulation with associated apparent cell necrosis and the mucin granule
      diameter was close to 1 microm. CONCLUSIONS: The ultrastructure of the mucin
      containing secretory granules of the conjunctival mucous cells is not necessarily
      homogeneous in character and further attention needs to be given to the effects
      of localised inflammation in the tissue and to possible hormonal influences.

PMID- 15575812
TI  - Quantification of dark adaptation dynamics in retinitis pigmentosa using non
      linear regression analysis.
AB  - PURPOSE: Non-linear regression analysis was used to determine dark adaptation
      indices in people with retinitis pigmentosa and in control subjects. METHODS:
      Dark adaptation data were collected for 13 people with retinitis pigmentosa and
      21 controls using the Goldmann-Weekers Dark Adaptometer. Data were analysed using
      an exponential non-linear regression model and dark adaptation indices derived.
      The results were compared to age-related values. RESULTS: The mean cone threshold
      of the group with RP (4.73 +/- 0.19 log units) was significantly greater than
      that found in the control group (3.69 +/- 0.12 log units). The rate of cone dark
      adaptation in the RP group was not significantly different from that of the
      control group. The a break in the RP group (6.46 +/- 0.70 minutes) was delayed
      when compared to the control group (4.29 +/- 0.21 minutes) and the rate of rod
      dark adaptation in the RP group was slower (10 +/- 2 per cent per minute) than
      that of the control group (15 +/- 1 per cent per minute). CONCLUSIONS: This study
      has shown that a relatively simple data analysis can provide a more quantitative
      and intuitive description of dark adaptation rates in people with retinal
      disease. This technique will enable more effective use of dark adaptometry as a
      supplement to objective electrophysiology, when monitoring people with retinitis
      pigmentosa.

PMID- 15575813
TI  - Solar retinopathy and associated optical coherence tomography findings.
AB  - Solar retinopathy is a rare but well-recognised clinical entity of macular
      damage, caused by viewing a solar eclipse or direct sun-gazing. Visual
      deterioration from solar retinopathy typically ranges from 6/9 to 6/60 and in
      most cases the visual loss is reversible. We present a case of solar retinopathy
      following direct sun-gazing and illustrate the damage within the retinal
      structure with optical coherence tomographic (OCT) findings. The visual prognosis
      of solar retinopathy is usually favourable but prevention remains the mainstay of
      treatment. The optometrist may play an important role in patient education and
      reassurance, as well as differentiating solar retinopathy from other likely
      macular abnormalities.

PMID- 15575814
TI  - Hemianopic visual field loss as the first clinical evidence of occipital
      arteriovenous malformation.
AB  - A 43-year-old patient presenting with a highly congruous homonymous hemianopia
      was shown by neuro-imaging to have a very large arteriovenous malformation of the
      brain. The significance of finding this visual field defect, its unusual cause
      and the absence of symptoms other than longstanding migraine with aura are
      discussed.

PMID- 15575815
TI  - Planning strategies for the rehabilitation of the partially sighted.

PMID- 15575816
TI  - Anthony J Gibson OAM: clinical teacher.

PMID- 15575817
TI  - Charles Bonnet syndrome: hallucinations may not be what they seem.

PMID- 15575818
TI  - Where would you send your mother for cataract surgery?

PMID- 15575819
TI  - The case of the disappearing red rose.

PMID- 15575820
TI  - Earlier report of superior oblique myokymia.

PMID- 15575822
TI  - An enigmatic eye: what can we learn?

PMID- 15575821
TI  - Functional studies of the 5'-untranslated region of human 5-HT4 receptor mRNA.
AB  - The serotonin 5-HT4 receptor (where 5-HT stands for 5-hydroxy-tryptamine) is a
      member of the seven transmembrane-spanning G-protein-coupled family of receptors
      and mediates many cellular functions both in the central nervous system and at
      the periphery. In the present study, we isolated and characterized the 5'
      flanking region of the h5-HT4 (human 5-HT4) receptor. We demonstrate the
      existence of a novel exon that corresponds to the 5'-untranslated region of the
      h5-HT4 receptor gene. RNase protection analysis and reverse transcriptase-PCR
      experiments performed on human atrial RNA demonstrated that the major
      transcription start site of the h5-HT4 receptor gene is located at -3185 bp
      relative to the first ATG codon. In addition, a 1.2 kb promoter fragment which
      drives the transcription of the 5-HT4 receptor was characterized. The promoter
      region lacks TATA and CAAT canonical motifs in the appropriate location, but
      contains putative binding sites for several transcription factors. Transient
      transfection assays revealed that the (-3299/-3050) gene fragment possesses the
      ability to promote the expression of the luciferase reporter gene in human cell
      lines. In contrast, the promoter was silent in monkey COS-7 cells, indicating the
      requirement of specific factors to initiate transcription in human cells. In
      addition to the promoter element, enhancer activity was found in a region (-220/
      61) located in the long 5'-untranslated region. Mutational analysis, gel shift
      and transfection assays identified an Nkx2.5 (NK2-transcription-factor-related 5)
      like binding site as a regulatory sequence of this enhancer. Our results suggest
      a complex regulation of the h5-HT4 receptor gene expression involving distinct
      promoters and non-coding exons.

PMID- 15575823
TI  - Is it time yet for intravitreal triamcinolone to be used in routine clinical
      practice?

PMID- 15575824
TI  - Clinical trial to compare efficacy and side-effects of injection of posterior sub
      Tenon triamcinolone versus orbital floor methylprednisolone in the management of
      posterior uveitis.
AB  - AIM: To compare the efficacy and side-effects of posterior sub-Tenon injection of
      triamcinolone acetonide (Kenalog) with orbital floor injection of
      methylpredisolone acetate (Depomedrone) in the management of posterior uveitis.
      METHODS: Non-randomized comparative prospective clinical study. Sixty-four eyes
      from 60 consecutive patients with non-infectious posterior uveitis requiring
      treatment were allocated on an alternate 1:1 basis to receive either orbital
      floor methylprednisolone or sub-Tenon triamcinolone using standard procedures and
      assessed at 6 and 12 weeks. RESULTS: After five eyes of five patients who had
      received the same treatment bilaterally were excluded from the statistical
      analysis, 14 out of 29 eyes treated with orbital floor methylprednisolone and 10
      out of the 30 eyes given sub-Tenon triamcinolone improved at 6 weeks. There was
      no statistically significant difference in the improvement rate between the two
      groups. However, two patients given triamcinolone had prolonged upper lid ptosis,
      which required surgery, and another two developed markedly raised intraocular
      pressure, neither of which occurred in the methylprednisolone-treated group.
      CONCLUSIONS: Although the two drugs and routes compared were of similar efficacy,
      lid ptosis occurred in the triamcinolone-treated but not the methylprednisolone
      group. This should be borne in mind when choosing the preferred route of delivery
      of periocular corticosteroid in the treatment of posterior uveitis.

PMID- 15575825
TI  - Intravitreal triamcinolone for diabetic macular oedema in Chinese patients: six
      month prospective longitudinal pilot study.
AB  - AIM: To evaluate the safety and efficacy of intravitreal triamcinolone (IVTA) in
      Chinese patients with diabetic clinical significant macular oedema (CSMO).
      METHODS: Eighteen eyes of 17 consecutive patients with CSMO were prospectively
      recruited and treated with a 4 mg injection of IVTA. Best-corrected visual acuity
      (BCVA) on the ETDRS chart and central macular thickness (CMT) on optical
      coherence tomography were measured at baseline weeks 1, 2, 3, and months 1, 2, 3,
      4, 5 and 6. Side-effects were monitored. RESULTS: All patients completed 6 months
      of follow up. The mean baseline BCVA and CMT were 1.20 +/- 0.31 logMAR units and
      552 +/- 179 microm, respectively. Improvements in CMT and BCVA were observed as
      early as at 1 and 2 weeks, respectively (P < 0.05). Mean BCVA peaked at 2 months
      (0.97 +/- 0.38 logMAR units) while mean CMT was maximally reduced at 3 months
      (326 +/- 145 microm). Improvements in BCVA and CMT were less afterwards but still
      statistically significant at 6 months; the final mean BCVA and CMT were 0.99 +/-
      0.36 logMAR units and 427 +/- 145 microm, respectively. A total of 5/18 (28%)
      eyes developed a transient increase in intraocular pressure. Cataract progression
      was noted in 2/12 (17%) of the phakic eyes. CONCLUSIONS: Intravitreal
      triamcinolone appeared generally safe and effective in Chinese patients with
      CSMO. Although the improvements in BCVA and CMT were transient, there were
      residual benefits at 6 months. Due to the transient nature of IVTA, re-treatment
      seems necessary but the optimal timing and dosage will require further
      investigations.

PMID- 15575826
TI  - Utilization of eye care services by Victorians likely to benefit from eye care.
AB  - AIM: To assess the utilization of eye care services by Australians most likely to
      benefit from eye assessment. METHODS: The Melbourne Visual Impairment Project was
      a population-based study that collected demographic, health and vision-related
      information including use of eye care services. A standardized detailed
      ophthalmic examination was performed. Utilization of eye care services by those
      who might most benefit from eye care was assessed and compared to the general
      population. These participants include those with undiagnosed glaucoma,
      unoperated visually significant cataract, undercorrected refractive error,
      diabetes mellitus, age-related macular degeneration and visual acuity < 6/12.
      Sociodemographic characteristics were assessed for their influence on eye care
      utilization among these participants. RESULTS: A total of 4744 urban and rural
      residents participated (86% of those eligible) and 4612 (83% of total eligible)
      of these had a complete data set for the use of eye care services and were
      included. There were 933 participants (20.2%) who did not report eye assessment
      in the previous 5 years, and 891 participants (19.3%) had one or more
      aforementioned conditions potentially benefiting from eye care. Of these, between
      34.4% and 59.4% reported no examination in the previous year and between 9% and
      25% reported no examination within the previous 5 years. These participants were
      more likely to seek eye care within the short term (1 year) if they had a family
      history of eye disease, otherwise a noticed change in vision was the main
      influence in the longer term (2-5 years). Male participants, younger participants
      and those whose main spoken language was not English were less likely to seek eye
      care in the longer term. CONCLUSIONS: In Victoria 19% of those >40 years of age
      have potentially unmanaged eye disease including glaucoma, unoperated visually
      significant cataract, undercorrected refractive error, age-related macular
      degeneration, diabetes mellitus or visual acuity < 6/12. A substantial proportion
      of these report no eye assessment in the previous 1, 2 or 5 years or ever before.
      Younger age, male sex and main language other than English make assessment less
      likely. Many may have these conditions despite having had a recent eye
      assessment.

PMID- 15575827
TI  - What is the direct cost of treatment of acute primary angle closure glaucoma? The
      Singapore model.
AB  - AIM: To estimate the cost of management of acute primary angle closure glaucoma
      in Singapore. METHODS: In this cost analysis using retrospective data, the
      authors performed a MEDLINE search of published papers on acute primary angle
      closure glaucoma (APACG) in Singapore. Using information from published data,
      clinical management pathways were constructed and clinical outcomes identified.
      For each management path, costs of medical treatment, hospitalization, clinic
      charges, investigations, laser treatment and surgery were identified and
      accounted over a 5-year treatment period, using year 2002 rates. RESULTS: Given
      that, in Singapore, APACG affects 12.2 per 100,000 per year (95% confidence
      interval [CI], 10.5-13.9) in those aged 30 and older, each annual cohort would
      need to pay 261,741.78 US dollars (95%CI: US$225 310.90-298 265.10) or 287,560.26
      US dollars (95%CI: 247,274.04-330,624.84 US dollars), if inclusive of cataract
      surgery, over 5 years after the episode of APACG. In this period, individuals
      would have to commit between 879.45 US dollars and 2576.39 US dollars, depending
      on the complexity of disease and accompanying cataract surgery. CONCLUSION: Acute
      primary angle closure glaucoma produces a substantial financial burden on society
      as well as on the individuals.

PMID- 15575828
TI  - Comparison of the Tono-Pen and Goldmann tonometer for measuring intraocular
      pressure in patients with glaucoma.
AB  - AIM: To estimate agreement between measurement of intraocular pressure (IOP) by
      the Tono-Pen and by the Goldmann tonometer. The hypothesis tested was that the
      mean difference in measurements would be <-2 mmHg. METHODS: A prospective, single
      centre, comparison study was carried out. The Tono-Pen was compared to the
      Goldmann tonometer in 138 patients systematically selected from two glaucoma
      clinics and among selected patients known to have high pressures (n = 22). For
      both groups the investigators were masked to the value of the Goldmann readings,
      the instruments were used in random order, and duplicated readings were taken
      with both tonometers. RESULTS: In the systematically selected group, for right
      eyes, the mean difference in measurement between the Tono-Pen and Goldmann
      tonometer was -0.41 mmHg (SD: 2.59). The 95% limits of agreement were -5.5 to 4.7
      mmHg, and the intraclass correlation coefficient (ICC) was 0.90. Results for left
      eyes were very similar. For patients with high pressures (> or =25 mmHg), the
      mean difference between instruments (Tono-Pen reading minus Goldmann reading):
      was -4.2 mmHg (P = 0.0004), SD: 4.6, 95% limits of agreement: -13.2 to 4.8 mmHg
      and ICC = 0.76. Combining the analysis for both groups, the Tono-Pen
      significantly underestimated the IOP when the pressure was >20 mmHg. CONCLUSIONS:
      The Tono-Pen cannot replace the Goldmann tonometer in the sense that it will give
      the same readings of IOP. The accuracy of the Tono-Pen is increased, if at least
      two measurements are taken per eye and then averaged.

PMID- 15575829
TI  - Glaucoma treatment in Australia: changing patterns of therapy 1994-2003.
AB  - AIM: To document the change in pattern of glaucoma treatment in Australia over
      the decade 1994-2003. METHODS: Observational study: retrospective data audit.
      RESULTS: The total number of prescriptions for glaucoma items has increased in
      this time period from 1.9 million to 3.3 million, with a cost increase to the
      Pharmaceutical Benefits Scheme (PBS) of in excess of 50m dollars. The largest
      increase has been in the class of prostaglandin analogues, which now comprise 49%
      of all glaucoma topical therapy prescriptions. Rates of laser trabeculoplasty and
      trabeculectomy surgery have fallen by 60% and 58%, respectively. Rates for
      secondary procedures such as repeat trabeculectomy, drainage implant devices and
      cycloablation have remained stable, although with some variation between
      Australian states. CONCLUSIONS: The introduction of multiple new medications has
      resulted in a decline in the amount of glaucoma surgery and laser trabeculoplasty
      performed. There has been an associated increase in the total number of glaucoma
      prescription items dispensed, and a large increase in the cost to the PBS of this
      change. Outcome measures of the benefit of these changes are lacking.

PMID- 15575830
TI  - Preventive effect of lacrimal occlusion on topical timolol-induced
      bronchoconstriction in asthmatics.
AB  - AIM: To evaluate the potential preventive role of lacrimal occlusion on the
      topical timolol-induced bronchoconstriction in asthmatics. METHODS: This was a
      prospective and single-masked study. Fourteen volunteer subjects with asthma were
      included. Collagen plugs were inserted into both canaliculi on one side to
      inhibit lacrimal drainage. The effect of lacrimal occlusion on lung function
      tests was measured before and 60 min after the instillation of a timolol drop in
      unplugged and plugged eyes. The spirometric measurements include forced vital
      capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, and mid
      expiratory flow-rate (FEF25-75). RESULTS: The timolol (0.5%) drop administration
      into the eye caused a significant decrease in pulmonary functions in patients
      with asthma in whom the lacrimal punctae had not been occluded by collagen plug.
      P values were 0.008 for FVC and 0.001 for FEV1 and FEF25-75. The occlusion of the
      lacrimal duct by intracanalicular plugs significantly reduced this decrease in
      pulmonary function. P values were 0.6 for FVC, 0.8 for FEV1, and 0.5 for FEF25
      75. The lacrimal occlusion did not affect heart rate and blood pressures. Three
      subjects complained of epiphora. CONCLUSIONS: Lacrimal occlusion with
      intracanalicular collagen plugs may almost completely prevent the
      bronchoconstriction caused by topical timolol in asthmatics by inhibiting or
      decreasing systemic absorption of the medication.

PMID- 15575831
TI  - Analysis of symptoms associated with rhegmatogenous retinal detachments.
AB  - AIM: The symptoms associated with rhegmatogenous retinal detachments are variable
      and can be associated with other vitreoretinal and neuro-ophthalmic entities. The
      present study sought to determine the frequency and type of symptoms associated
      with rhegmatogenous retinal detachment (RRD), and analyse any relationships with
      the premorbid state. METHODS: An observational case series was undertaken. A
      patient questionnaire together with clinical data was collected for patients
      presenting with RRD. RESULTS: The data on 141 patients presenting with RRD were
      evaluated prospectively. More than 90% of patients reported a variety of symptoms
      including visual loss, floaters and flashes. The speed of visual loss was not
      associated with the extent of retinal break. Rather unexpectedly, patients with a
      history of retinal pathology were not any more likely to be symptomatic either in
      their presenting or fellow eye. The absence of symptoms was not associated with
      age, high myopia or previous cataract surgery. CONCLUSION: Both patients and
      physicians need to be aware of the importance of the symptoms associated with
      RRD.

PMID- 15575832
TI  - Analysis of New Zealand's research productivity in ophthalmology and vision
      science: 1993-2002.
AB  - AIM: To assess New Zealand's research productivity in the area of ophthalmology
      and vision science over the decade 1993-2002. METHODS: New Zealand-based
      researchers involved in ophthalmology or vision science research, including
      ophthalmologists, optometrists and vision scientists were identified via
      professional colleges, universities and electronic databases. Peer-reviewed
      publications by these authors were identified by both searching electronic
      databases (MEDLINE/Pubmed) and personal communication with individual
      researchers. RESULTS: Eighty-five New Zealand-based researchers involved in
      ophthalmology or vision science research published 446 articles in 84 scientific
      journals during the 10-year period. The cohort consisted of 59 ophthalmologists
      and 26 other researchers based in a diverse range of ophthalmology, optometry and
      university departments. Significant collaboration was observed between groups
      within New Zealand and with international institutions. Comparing
      ophthalmologists and 'other' researchers, ophthalmologists produced 69% of all
      ophthalmology and vision science research publications and those classified as
      'active ophthalmologist researchers' published an average of 11 (range 5-55)
      papers each during this decade, compared to eight (range 5-25) for the group
      'other active researchers'. This was also reflected in the high productivity rate
      by ophthalmologists of 277 publications per 1000. Publications were identified in
      a wide range of journals with the majority in top 20-ranked ophthalmology
      journals. The trend over the decade highlighted an increase in number of
      scientific publications, from 43 per annum in 1993, to 68 per annum in 2002.
      CONCLUSIONS: Despite a relatively small and geographically isolated population,
      New Zealand ophthalmology and vision science research is highly active and
      collaborative, with significantly increased research productivity during the
      period 1993-2002. The present study is the first to document these trends and
      provides strong evidence to justify continued support for ophthalmology and
      vision science research in New Zealand.

PMID- 15575833
TI  - New vehicle based on a microemulsion for topical ocular administration of
      dexamethasone.
AB  - AIM: Eye drops are the most used dosage form by the ocular route, in spite of
      their low bioavailability. Due to their properties and numerous advantages,
      microemulsions are promising systems for topical ocular drug delivery. They can
      increase water solubility of the drug and enhance drug absorption into the eye.
      The present study describes the development and characterization of an oil-in
      water microemulsion containing dexamethasone and the evaluation of its
      pharmacokinetics in rabbits after topical ocular application. METHODS: The
      microemulsion was prepared by the titration technique. Its physico-chemical
      characteristics and stability were determined. The ocular irritation test and the
      pharmacokinetics of this system were studied in white rabbits. RESULTS: The
      developed system showed an acceptable physico-chemical behaviour and presented
      good stability for 3 months. The ocular irritation test used suggested that the
      microemulsion did not provide significant alteration to eyelids, conjunctiva,
      cornea and iris. This formulation showed greater penetration of dexamethasone in
      the anterior segment of the eye and also release of the drug for a longer time
      when compared with a conventional preparation. The area under the curve obtained
      for the microemulsion system was more than twofold higher than that of the
      conventional preparation (P < 0.05). CONCLUSIONS: The microemulsion-based
      dexamethasone eye drop is advantageous for ophthalmic use because it is well
      tolerated in the eye and seemed to provide a higher degree of bioavailability.
      The developed system shows greater penetration in the eye, allowing the
      possibility of decreasing the number of applications of eye drops per day.

PMID- 15575834
TI  - Application of physical principles in the development of tonometry.
AB  - A review of the development of applanation tonometry is undertaken from the
      perspective of the physical principles involved. Original articles that have
      contributed to this process are discussed. The result of this endeavour leads to
      a conclusion that corneal thinning procedures have no effect on original
      intraocular pressure. Also concluded is a methodology that would allow the direct
      measurement of original intraocular pressure.

PMID- 15575835
TI  - 'Ancient' schwannoma of the orbit.
AB  - A 65-year-old woman presented with a 3 month history of right eye discomfort and
      protrusion. Examination revealed right proptosis with hypoglobus and diplopia in
      extremes of upgaze. Computed tomographic scanning revealed a large extraconal
      mass in the superotemporal orbit. The mass was excised through an extended
      superior skin crease incision. Histopathology revealed a benign tumour of Schwann
      cell origin showing advanced cystic degeneration, the so-called 'ancient
      schwannoma'. The authors could find only two previously reported cases of such
      tumours arising in the orbit.

PMID- 15575836
TI  - Developments in the management of uveal melanoma.
AB  - Uveal melanomas threaten visual loss, enucleation, and death from metastatic
      disease. Most patients present because of symptoms, but failures of detection and
      diagnosis still occur commonly. Treatments aimed at avoiding enucleation include:
      plaque, proton beam or stereotactic radiotherapy; trans-scleral or trans-retinal
      local resection; and transpupillary thermotherapy. Increasingly, different
      modalities are being used in combination. The ocular outcomes are related to
      tumour size, location, spread and cell type. Metastatic disease occurs in many
      patients and is related to factors such as tumour dimensions, ciliary body
      involvement, cell type, extravascular matrix patterns and cytogenetics.
      Abnormalities related to chromosomes 3, 6 and 8 are strongly related to tumour
      behaviour, for the first time enabling survival probability to be estimated with
      a high degree of reliability in an individual patient. This enables high-risk
      individuals to be targeted for screening while providing reassurance to those
      with a minimal chance of developing metastatic disease. Such targeting would
      allow selection of patients for adjuvant systemic therapy, should a suitable
      treatment become available, and would also facilitate the evaluation of such
      treatment by increasing the statistical power of any randomized prospective
      study. The high mortality in patients with monosomy 3 melanoma suggests that in
      these patients ocular treatment is only palliative. Cytogenetic studies suggest
      that some melanomas may never develop any metastatic potential and if these
      impressions are confirmed by further studies, then in these patients the main
      priority of treatment would be to conserve vision.

PMID- 15575837
TI  - Orbital lymphoid tumour located within an extraocular muscle.
AB  - A rare case of an orbital lymphoid tumour within an extraocular muscle is
      presented. The tumour displayed features of a progressive indolent systemic
      lymphoma. There was no response to a trial of chemotherapy and so local
      radiotherapy was instituted. At follow up 2 months later there was no evidence of
      disease.

PMID- 15575838
TI  - Recurrent posterior capsular opacification and capsulorhexis contracture after
      cataract surgery in myotonic dystrophy.
AB  - Cataracts are well known to be associated with myotonic dystrophy. Less well
      known are the phenomena of recurrent posterior capsule opacification and
      capsulorhexis contracture post cataract surgery. Two cases are described herein
      of postoperative capsular complications requiring multiple capsulotomies in
      patients with myotonic dystrophy. It is proposed that a common aetiology may
      underlie both posterior capsule opacification and capsulorhexis contracture in
      myotonic dystrophy cases.

PMID- 15575839
TI  - Comment on 'Glaucoma from topical corticosteroids to the eyelids'.

PMID- 15575840
TI  - Effective draping for cataract surgery by using a relieving incision in the
      operative drape.

PMID- 15575841
TI  - Benzalkonium toxicity.

PMID- 15575842
TI  - Serum concentration of IL-18 correlates with disease extent in young children
      with atopic dermatitis.
AB  - Interleukin (IL)-18 is a pleiotropic cytokine that plays an important role in
      both type 1 (Th1) and type 2 (Th2) helper T lymphocyte-mediated immunity.
      Previous studies have suggested that IL-18 may be an inflammatory marker for
      atopic dermatitis (AD). The purpose of our study was to test whether the serum
      concentration of IL-18 is a useful inflammatory marker for assessing AD severity
      in young children. Nineteen AD patients with a median age of 2.2 years
      (interquartile range 0.7-4.6 years) were recruited. The severity of AD was
      clinically determined using the Scoring Atopic Dermatitis (SCORAD) index. Their
      SCORAD score was 23.9 (range 18.6-34.8). Serum IL-18 levels were determined by
      sandwich enzyme immunoassay. The median serum concentration of IL-18 was 394
      pg/ml (interquartile range 204-612 pg/ml). Serum IL-18 levels correlated with
      SCORAD scores (r = 0.502, p = 0.029) and their extent component (r = 0.633, p =
      0.004). When compared with mild disease with low SCORAD scores, the serum
      concentration in moderate to severe disease was significantly higher (p = 0.014).
      We concluded that serum IL-18 concentration is elevated in young children with
      AD. It may be a useful inflammatory marker that correlates with the extent
      component of AD in particular, and differentiates mild disease from more severe
      disease when used for assessing AD severity in young children.

PMID- 15575843
TI  - Time spent on treatment of atopic dermatitis: a new method of measuring pediatric
      morbidity?
AB  - Our purpose was to examine if the time spent on treatment (TSOT) is a relevant
      surrogate measure of pediatric disease severity. The TSOT (min/day) was studied
      in a group of 42 children with atopic dermatitis (AD) (16 girls and 26 boys; mean
      age 7.07 years). The TSOT included time spent on all types of topical treatment,
      on extra cleaning, and on visits to doctors. Objective Scoring Atopic Dermatitis
      (SCORAD) assessment was performed at each visit. A significant correlation was
      found between TSOT and SCORAD scores for all visits (p < 0.0001). There was no
      correlation between TSOT and age or sex or between TSOT/SCORAD and age (p <
      0.08). For the 65 visits (by 42 children), TSOT/SCORAD ranged from 0.08 min/point
      to 28.67 min/point. Older children (10-15 years of age) had a lower TSOT/SCORAD
      ratio compared to younger children (1-5 years of age). Our data suggest that TSOT
      in itself may be a useful measure of morbidity among pediatric AD patients. It is
      speculated that patients with a very high TSOT/SCORAD rate or a very low rate
      have coping problems and would therefore be suitable candidates for intensified
      efforts in programs such as "eczema schools."

PMID- 15575844
TI  - Patient demographics and utilization of health care services for molluscum
      contagiosum.
AB  - Our objective was to describe the demographics of molluscum contagiosum patients
      and physician utilization patterns in the United States. We obtained weighted
      data for office visits throughout the United States for molluscum contagiosum and
      common warts from the National Ambulatory Medical Care Survey (NAMCS) from 1990
      to 1999. Outpatient visit data for patients diagnosed with molluscum contagiosum
      were analyzed using statistical software and compared to those for patients
      diagnosed with common warts. The main outcome measures studied were physician
      office visits by patients with molluscum contagiosum and patient demographic
      parameters including age, gender, and race. We found that health care utilization
      for molluscum contagiosum was the greatest for patients <or=9 years of age (51%).
      Ninety-three percent of patients diagnosed with molluscum contagiosum were white.
      The number of visits for molluscum contagiosum was evenly divided between males
      and females. Visits to dermatologists comprised the majority of health care
      utilization units for molluscum contagiosum (71%). In conclusion, visits for
      molluscum contagiosum are frequent and are most often handled by dermatologists.
      When compared to those for common warts, molluscum contagiosum visits are less
      common and have an age distribution more limited to children.

PMID- 15575845
TI  - Cutaneous adverse reactions to hydroxyurea in patients with intermediate
      thalassemia.
AB  - Although the cutaneous effects of hydroxyurea have been described for patients
      with sickle cell anemia, myeloproliferative disorders, and psoriasis, there are
      no reports of cutaneous adverse effects from hydroxyurea when used for patients
      with intermediate thalassemia. Therefore 43 patients with intermediate
      thalassemia treated with hydroxyurea were examined by a dermatologist, and
      pertinent cutaneous findings were recorded. These patients had received
      hydroxyurea for a mean of 15.5 months. Nineteen had cutaneous hyperpigmentation,
      eight had xerosis, and three were found to have one cafe au lait macule each.
      Eleven patients had nail abnormalities, including nail ridging, partial
      leukonychia, and longitudinal melanonychia. There were no cases of leg
      ulceration. It was concluded that the risk of developing leg ulcers and
      pigmentary disorders appears to be related to the underlying disease being
      treated, as well as to a patient's age, gender, and pigmentation.

PMID- 15575846
TI  - Postnatal confirmation of prenatally diagnosed trisomy 20 mosaicism in a patient
      with linear and whorled nevoid hypermelanosis.
AB  - Linear and whorled nevoid hypermelanosis (LWNH) is characterized by
      hyperpigmented reticulate macules in a Blaschko linear arrangement without
      atrophy or preceding inflammation. Underlying chromosomal mosaicism was often
      assumed, but has been verified in only a few published cases. We report a 7-year
      old boy with LWNH associated with congenital ventricular septal defect and
      psychomotor retardation. Prenatal chromosomal analysis of amniocytes revealed
      trisomy 20 mosaicism, which was not confirmed in peripheral blood lymphocytes
      after birth. Histologic sections of skin biopsy specimens taken at age 6 years
      showed hyperpigmentation of the basal epidermal layer with prominent melanocytes
      and isolated melanophages in the upper dermis. Cytogenetic analysis of cultured
      skin fibroblasts revealed an extra chromosome 20 in 5 of the 30 metaphases
      studied (17%). Mosaic trisomy 20 is one of the most common autosomal mosaicisms
      identified in amniocytes and is, as a rule, compatible with normal pregnancy
      outcome. In postnatal analysis of peripheral blood lymphocytes, an extra
      chromosome 20 could never be detected. However, when confirmed in skin
      fibroblasts, trisomy 20 mosaicism may be associated with systemic anomalies. The
      present case shows for the first time an association of LWNH with trisomy 20
      mosaicism and emphasizes the importance of analyzing skin fibroblasts in cases of
      prenatally diagnosed trisomy 20.

PMID- 15575847
TI  - Phakomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome.
AB  - We describe a 23-month-old child with phakomatosis pigmentovascularis type IIb
      associated with Sturge-Weber syndrome. Phakomatosis pigmentovascularis type IIb
      is a rare cutaneous malformation characterized by the simultaneous occurrence of
      nevus flammeus and melanocytic nevi. A brief review of the literature is
      presented and classification of this rare disease is discussed.

PMID- 15575848
TI  - Lymphadenopathy after BCG vaccination in a child with chronic granulomatous
      disease.
AB  - We report a 15-month-old boy who developed an ulcer in the left axillary fold
      following bacillus Calmette-Guerin vaccination. Subsequent immunologic and
      genetic studies led to the diagnosis of chronic granulomatous disease. His mother
      had "lupus-like" lesions, described in some carriers of this disease, that were
      thus related to her son's diagnosis. Although in healthy subjects this
      vaccination is usually harmless, in instances of impaired immunity it may cause
      adverse reactions. When a vaccine-related complication occurs, an underlying
      immunodeficiency should be sought.

PMID- 15575849
TI  - Lymphangioma circumscriptum: an example of Whimster's hypothesis.
AB  - Lymphangioma circumscriptum is an uncommon hamartomatous malformation that is not
      only localized to an area of skin, but also spreads to subcutaneous tissue and
      muscle (Whimster's hypothesis). We describe a 7-year-old boy with a bluish plaque
      on the left side of the back and abdomen with clusters of translucent vesicles
      (frog spawn). Magnetic resonance imaging showed the lymphangioma had spread to
      muscles and even fat adjacent to the left kidney. We decided against radical
      surgery as it would have been too aggressive, and limited excision can produce
      new surface lymphangiomas.

PMID- 15575850
TI  - Precalcaneal congenital fibrolipomatous hamartomas: report of occurrence in half
      brothers.
AB  - Precalcaneal congenital fibrolipomatous hamartomas are uncommon, congenital,
      nontender papules located on the medial plantar aspects of the heel. We report
      the occurrence of this rare disorder in two half brothers, suggesting that it may
      occur in a familial pattern.

PMID- 15575851
TI  - Carotenemia associated with green bean ingestion.
AB  - Carotenemia is a condition characterized by yellow discoloration of the skin and
      elevated blood carotene levels. Excessive and prolonged ingestion of carotene
      rich, yellow- or orange-colored foods such as carrots and winter squash is the
      most common cause, but more rarely it may be associated with consumption of other
      foods as well as with hypothyroidism, diabetes mellitus, anorexia nervosa, liver
      disease, or kidney disease. Though not uncommon in children, there are few
      reports in the pediatric literature since its early descriptions in the late
      1800s and early 1900s. Awareness of carotenemia can help the provider resolve
      confusion with jaundice and avoid unnecessary worry and costly tests. Herein we
      describe carotenemia in an 8-month-old Caucasian girl secondary to increased
      consumption of commercial infant food green beans.

PMID- 15575852
TI  - Pulmonary tuberculosis and cutaneous mycobacterial infection in a patient with
      incontinentia pigmenti.
AB  - Lupus vulgaris is reinfection tuberculosis of the skin and may result from direct
      extension, or hematogenous or lymphatic spread from a tuberculosis focus. Lupus
      vulgaris following bacille Calmette-Guerin (BCG) vaccination is a rare entity.
      Incontinentia pigmenti is an X-linked dominant genodermatosis in which vesicular,
      verrucous, and pigmented lesions are associated with various developmental
      defects. There is evidence of altered immunologic reactivity in some patients
      with incontinentia pigmenti. A 12-year-old girl hospitalized for pulmonary
      tuberculosis presented with bizarre-shaped brown macules following Blaschko lines
      on the left deltoid area, compatible with incontinentia pigmenti, which had
      appeared following BCG vaccination at the age of 7 years. Histopathologic
      examination found noncaseated granulomas in the dermis. Antituberculous treatment
      for pulmonary and cutaneous tuberculosis was initiated along with genetic
      counseling. Immunologic abnormalities have been reported in conjunction with
      incontinentia pigmenti. Simultaneous occurrence of pulmonary and cutaneous
      tuberculosis in our patient might be either coincidental or indicate derangements
      in the cellular immune system.

PMID- 15575853
TI  - An unusual cutaneous lesion as the presenting sign of spinal dysraphism in a
      preterm infant.
AB  - We present a preterm female infant with an unusual vascular nevus on the
      lumbosacral and gluteal regions. Our clinical diagnosis was probable twin nevus,
      with a blanched nevus adjacent to a telangiectatic nevus, later complicated by
      ulceration. Ultrasonography and magnetic resonance imaging of the lumbosacral
      region revealed that her conus medullaris level was at L4 and the spinal cord was
      tethered by an intraspinal lipoma, without evidence of a hemangioma. We could not
      find any literature reporting the association of twin nevus with spinal
      dysraphism.

PMID- 15575854
TI  - Generalized bullous impetigo in a neonate.
AB  - Generalized bullous impetigo is uncommon in healthy and term neonates. It must be
      differentiated from staphylococcal scalded skin syndrome and other commonly
      encountered vesiculopustular lesions. We report generalized bullous impetigo in
      an otherwise healthy neonate.

PMID- 15575855
TI  - Efficacy of a reduced application time of Ovide lotion (0.5% malathion) compared
      to Nix creme rinse (1% permethrin) for the treatment of head lice.
AB  - Our objective was to conduct a randomized, investigator-blinded evaluation of the
      pediculicidal and ovicidal activity of a reduced application time (20 minutes) of
      Ovide (0.5% malathion) compared to Nix (1% permethrin) in a south Florida
      population infested with Pediculus humanus capitis. Either Ovide or Nix was
      applied according to the label instructions. However, Ovide application time was
      reduced to 20 minutes. At day 8, subjects with live lice were re-treated with the
      same product and procedure as on day 1. Ovicidal and pediculicidal efficacy were
      evaluated at days 8 and 15. A subject free of lice and viable eggs at day 15 was
      considered to be a treatment success. Percent efficacy was calculated using the
      number of subjects free of lice and viable eggs per total number of subjects
      treated. We found that a 20-minute application of Ovide was significantly more
      pediculicidal and ovicidal (98%) compared to Nix (55%) at day 15 (p < 0.0001).
      The percentage of Ovide subjects who required treatment at day 8 was half that of
      the Nix group. The reinfestation rate was 0% with Ovide and 33% with Nix. In
      conclusion, a 20-minute treatment with Ovide, instead of the approved 8- to 12
      hour application, cured 40 of 41 subjects (98%), demonstrating superior efficacy
      to Nix. The poor efficacy of Nix confirms the resistance of head lice to
      permethrin in south Florida.

PMID- 15575856
TI  - Voriconazole-induced retinoid-like photosensitivity in children.
AB  - Voriconazole is a new triazole antifungal agent with activity against a wide
      range of systemic fungal pathogens, including Aspergillus spp. Photosensitivity
      is a rarely reported side effect of voriconazole, hypothesized to be a result of
      retinoid-like effects. We report two children with chronic granulomatous disease
      to whom voriconazole was administered for chronic invasive aspergillosis. Severe
      photosensitivity occurred in both patients, one of whom had striking photodamage
      at the 5-month follow-up.

PMID- 15575857
TI  - What syndrome is this? Hunter Syndrome.

PMID- 15575858
TI  - Unilateral linear annular lesions in a child.

PMID- 15575859
TI  - Sjogren-Larsson syndrome in an Indian child.

PMID- 15575860
TI  - Granular parakeratosis.

PMID- 15575863
TI  - Review article: prevalence and epidemiology of gastro-oesophageal reflux disease.
AB  - There are considerable uncertainties around the definition and the appropriate
      clinical diagnostic criteria for gastro-oesophageal reflux disease (GERD), a
      common condition that appears to be increasing in prevalence in the Western
      world. Prevalence studies of GERD are hampered by whether any heartburn symptom
      is included, or just predominant or even 'sole' heartburn, and also by the time
      frame over which the symptoms have been evaluated. A systematic search of Medline
      using the keywords 'GERD' 'prevalence' and 'community' yielded three papers, two
      original articles and one systematic review of studies that surveyed symptoms in
      unselected subjects. Heartburn is a common symptom in Europe ranging from a
      prevalence of 38% in Northern Europe to 9% in Italy. Comparable 6-month data from
      the USA suggest an even higher prevalence with a rate of 42%. GERD is also a long
      term, relapsing disorder. A population survey in Sweden found GERD symptoms over
      time at 18% of the population surveyed. In summary, although symptoms and quality
      of life improve with acid suppression therapy, costs are high and the potential
      benefit of long-term treatment is rare, but serious complications of GERD are
      unknown.

PMID- 15575864
TI  - Review article: prevalence and epidemiology of gastro-oesophageal reflux disease
      in Japan.
AB  - The prevalence of gastro-oesophageal reflux disease (GERD) in Asian populations
      is reported to be lower than that in Western populations. However, recent
      epidemiological studies suggest that the incidence of the disease is increasing,
      especially in Japan. Endoscopic studies show that the overall prevalence of
      reflux oesophagitis among the adult population in Japan is in the region of 14
      16%. This is similar to the figure reported in Western countries. The increasing
      prevalence in Japan may be due to a number of factors including increasing
      awareness of the condition and improved diagnostic techniques. The majority of
      the diagnosed cases in Japan are mild and these account for the increase in
      prevalence of the condition. In contrast to the West, where the condition is more
      prevalent in male members of the population, there is a high incidence of GERD in
      elderly females in Japan. The increased incidence of kyphosis and osteoporosis in
      this population may lead to the development of hiatus hernia, a condition known
      to exacerbate the development of reflux disease. Furthermore, Japanese patients
      with endoscopically diagnosed GERD appear to be less likely to complain of
      typical reflux symptoms, such as heartburn and acid reflux than their Western
      counterparts. In view of the known relationship between asymptomatic GERD and the
      development of oesophageal cancers there is a strong case for increased vigilance
      in the detection of GERD in the Japanese population.

PMID- 15575865
TI  - Review article: diagnosis and clinical investigation of gastro-oesophageal reflux
      disease: a European view.
AB  - In Western populations, many individuals with symptoms of gastro-oesophageal
      reflux disease (GERD) do not bother to seek medical attention because their
      symptoms are mild and acceptably controlled by self-medication. Among those who
      do consult physicians, only a minority present with the classical clinical
      symptoms of heartburn and regurgitation: more often the pattern is a nonspecific
      combination of upper gastrointestinal complaints that do not permit confident
      clinical diagnosis. Oesophagitis is now found in less than 50% of GERD patients
      and those without oesophagitis are sometimes said to have 'non-erosive reflux
      disease'. If a patient's clinical history is inadequate for diagnosis and the
      oesophageal endoscopic appearances are normal, ambulatory pH monitoring may be
      required if the diagnostic uncertainty is to be resolved. Despite initial
      enthusiasm, the 'Proton Pump test' for GERD has proved unreliable and has fallen
      from favour. Intraluminal impedence measurement is currently considered a
      research tool only. Most European gastroenterologists acknowledge the occurrence
      of 'atypical' presentations of GERD, including noncardiac chest pain, asthma and
      hoarseness (laryngitis), though confirmation of GERD as the cause of such
      symptoms in individual patients is often difficult.

PMID- 15575866
TI  - Review article: diagnosis and investigation of gastro-oesophageal reflux disease
      in Japanese patients.
AB  - Gastro-oesophageal reflux disease (GERD) encompasses a wide range of disorders
      defined by either reflux-related symptoms or by complications of gastro
      oesophageal reflux. The most characteristic GERD symptoms are heartburn and acid
      regurgitation. Patients with these symptoms are in most cases easily identifiable
      and diagnosis is made on the basis of symptoms alone. For patients with a
      decreased frequency of heartburn, diagnosis is more difficult, and endoscopy is
      the single best test for diagnosis of GERD. A major difference between the West
      and Asia is the frequency of endoscopic investigation. In Japan, the earlier high
      prevalence of stomach cancers resulted in the increased use of endoscopy as an
      investigational tool for dyspeptic symptoms and today endoscopy continues to be
      widely available as a diagnostic tool. However, the overall sensitivity of
      endoscopy for the diagnosis of GERD is less than 50% since not all patients will
      have oesophagitis at the time of endoscopy. Ambulatory pH monitoring is therefore
      a frequently used diagnostic tool as it allows correlation between reflux events
      and symptoms, and is especially useful in patients with atypical or
      extraoesophageal symptoms. Oesophageal manometry is also an excellent test to
      evaluate oesophageal function and to measure sphincter pressure and while it may
      not provide an unequivocal diagnosis of GERD it is a useful tool with which to
      evaluate oesophageal function.

PMID- 15575867
TI  - Review article: treatment for gastro-oesophageal reflux disease--lifestyle advice
      and medication.
AB  - Management of gastro-oesophageal reflux disease (GERD) is aimed at reducing
      oesophageal acid exposure to achieve symptom relief. Therapy has traditionally
      included advice to the patient on diet and lifestyle management. Recent evidence
      suggests, however, that some specific dietary modifications may be applicable to
      the Japanese patient. For example, ingestion of Japanese sweet cakes or rice
      cakes should be avoided by the Japanese patient with GERD as these foods may
      provoke heartburn. Pharmacological therapy is, however, usually also required for
      effective symptom relief. While antacids and histamine H(2)-receptor antagonists
      have a role in treating mild GERD, effective relief of many cases of oesophagitis
      is usually only achieved by using proton-pump inhibitors such as lansoprazole,
      omeprazole and rabeprazole. In the Japanese population, variation in the genetic
      polymorphism of CYP2C19 (a cytochrome P450 isoenzyme) leads to considerable inter
      individual unpredictability in the activity of lansoprazole and omeprazole due to
      inter-individual differences in the extent to which these agents are metabolized.
      Consequently, rabeprazole, which does not undergo hepatic biotransformation by
      CYP2C19, offers significant advantages over the other PPIs as a result of its
      more predictable activity. This, coupled with its more rapid onset of action,
      leads to a more efficient and less variable acid-suppressing effect.

PMID- 15575868
TI  - Review article: the patient with gastro-oesophageal reflux disease--lifestyle
      advice and medication.
AB  - Gastro-oesophageal reflux disease (GERD) is a highly prevalent disorder in all
      Western countries. Interestingly, prevalence rates appear to be increasing in
      these countries, with a remarkable increase of GERD-related lethal and nonlethal
      complications. However, these complications are rare on a global scale. This
      review aims to summarize the current concepts of genetic, lifestyle and
      environmental factors that need to be considered whilst caring for patients with
      these disorders. GERD is defined by the augmented exposure of oesophageal mucosa
      to acidic content, and is associated with specific symptoms or mucosal lesions. A
      number of factors may contribute to the manifestation of GERD. Although recent
      studies emphasize the role of genetic factors, there are many other risk factors
      that play a pivotal role in the development of GERD and GERD complications. Some
      nutritional factors are believed to aggravate acidic reflux either by delaying
      gastric emptying or diminishing the pressure of the lower oesophageal sphincters.
      Patients are often advised to sleep with their heads elevated, but this advice is
      not easy to follow and has not been proven effective with regard to long-term
      outcome. Other lifestyle modifications include changes to the patient's diet,
      which are important but not frequently sufficient. Thus, medication is usually
      necessary for symptom control. Proton pump inhibitors are now mainstream
      treatment for the reduction of acid secretion in patients with severe
      manifestations and 4-week healing rates are approaching 90%.

PMID- 15575869
TI  - Review article: surgical and endoscopic therapy of gastro-oesophageal reflux
      disease in Japan.
AB  - Treatment of gastro-oesophageal reflux disease (GERD) with lifestyle changes to
      avoid the conditions that make the symptoms worse and medication to lower the
      acid content of the refluxed material are generally very effective therapies.
      However, some individuals do not benefit enough from these approaches, and
      surgical intervention is warranted. Laparoscopic surgery is the procedure of
      choice among surgeons performing operations for reflux disease. This surgical
      technique allows for shorter hospitalization, fewer post surgical complications
      and less pain than open surgery while maintaining a high success rate. Data from
      Japan confirms that laparoscopic fundoplication is a safe and effective technique
      for controlling both typical and atypical symptoms of GERD. Recently, several
      endoscopic or luminally delivered techniques have been developed as an
      alternative to laparoscopic surgery. These new surgical options, currently under
      evaluation in Japan, may offer a valuable alternative to patients who are not
      responsive to, or who do not wish to persist with lifelong medical therapy for
      GERD.

PMID- 15575870
TI  - Review article: indications for anti-reflux surgery and endoscopic anti-reflux
      procedures.
AB  - Gastro-oesophageal reflux disease is a motor disorder principally caused by
      defective function of the lower oesophageal sphincter. Proton pump inhibitor
      (PPI) drugs alleviate symptoms, heal oesophagitis and improve quality of life but
      do not address the underlying motor disorder, and prolonged treatment is often
      needed. The efficacy of anti-reflux operations is comparable to PPIs. Indications
      for surgical referral include ineffective medical therapy, intolerance to PPIs,
      the aspiration to avoid drugs and treatment of complications (particularly peptic
      stricture and respiratory diseases). Pre-operative assessment should include
      endoscopy, pH monitoring and oesophageal manometry. The efficacy of anti-reflux
      surgery is well established but endoscopic anti-reflux procedures currently have
      an uncertain role. These procedures are based on endoscopic suturing, injection
      of materials around the lower oesophageal sphincter and radio frequency ablation.
      Published series show that all procedures may be effective in selected patients.
      Although the mechanisms for this efficacy are unclear, they may include
      correction of the underlying motor defect, physical barrier to reflux and
      decreased oesophageal sensitivity caused by denervation. Comparative studies are
      needed before endoscopic anti-reflux procedures can be recommended outside of
      clinical trials.

PMID- 15575871
TI  - Review article: Helicobacter pylori and gastro-oesophageal reflux disease--the
      European perspective.
AB  - There is substantive epidemiological evidence of a negative association between
      Helicobacter pylori infection and reflux disease and its malignant complications.
      A plausible mechanism by which the infection might protect against reflux disease
      is by its propensity to produce atrophic gastritis and consequently reduce
      gastric acid secretion. Gastric acid is a key factor in the pathophysiology of
      reflux oesophagitis. It is well recognised that acid secretion decreases with age
      in H. pylori infected populations whereas acid secretion is maintained throughout
      life in H. pylori negative populations. The tendency for H. pylori infection to
      induce atrophy and reduce acid secretion is more marked in Eastern Europe and the
      Far East than in Western Europe, and this may be due to the influence of
      environmental and host genetic co-factors. This difference may also explain why
      the negative association between H. pylori infection and reflux disease is more
      marked in these areas than in Western Europe. If H. pylori infection is indeed
      protecting against reflux disease, then one would predict a rise in incidence of
      this disease and its malignant complications in these Eastern countries as the
      incidence of H. pylori infection decreases.

PMID- 15575872
TI  - Review article: influence of Helicobacter pylori on gastro-oesophageal reflux
      disease in Japan.
AB  - There is circumstantial evidence that infection with Helicobacter pylori is
      relatively protective for the occurrence of gastro-oesophageal reflux disease
      (GERD). It has been suggested that the Japanese population are protected against
      reflux oesophagitis by their high prevalence of H. pylori associated gastritis.
      Such gastritis, when becoming chronic, can lead to gastric atrophy, thereby
      reducing the likelihood of GERD. If this hypothesis is correct, the effects of H.
      pylori induced gastritis may be an important factor determining the earlier lower
      prevalence of oesophagitis in Japan, where this infection is especially common.
      In support of this idea a reduced prevalence of H. pylori infection in Japan, as
      is now being observed in young Japanese adults, may be, at least in part,
      responsible for the upsurge in the number of cases of reflux disease in Japan.
      Concomitantly, H. pylori eradication therapy in patients with gastritis or peptic
      ulcer disease, which is associated with an increase in gastric acid secretion,
      may also be at least partly responsible for the increased prevalence of reflux
      oesophagitis in the Japanese population.

PMID- 15575873
TI  - Review article: Barrett's oesophagus and associated adenocarcinoma--a UK
      perspective.
AB  - In the UK and across the Western world there has been a rapid increase in
      oesophageal adenocarcinoma, such that this cancer is now more common than
      squamous cell carcinoma. The 5-year mortality from oesophageal adenocarcinoma is
      >80% and therefore there has been increasing interest in the pre-malignant
      condition Barrett's oesophagus. Barrett's oesophagus is defined by a visible
      columnar-lined segment with histopathological evidence of a glandular epithelium,
      which typically contains intestinal metaplasia. Once Barrett's oesophagus is
      diagnosed, most centres in the UK offer endoscopic surveillance with the aim to
      detect early, curable lesions. Surveillance in its current form is cumbersome and
      expensive, and new endoscopic and molecular developments are hoped to improve the
      yield of such procedures. The current treatments are symptomatic control of
      reflux symptoms, with more definitive treatments usually reserved for patients
      with at least high-grade dysplasia. There is interest in chemoprevention
      strategies, including proton-pump inhibitors, cyclo-oxygenase-2 inhibitors and
      aspirin, but to date none of these have proven effective. Treatment options for
      high-grade dysplasia include surgery, endoscopic mucosal resection (in the
      context of a visible lesion) and photodynamic therapy. Comparative studies
      between various geographical regions, as the predominant histopathological
      subtypes of oesophageal cancer change, may give us some clues about the
      pathogenesis of Barrett's adenocarcinoma.

PMID- 15575874
TI  - Review article: Barrett's oesophagus and carcinoma in Japan.
AB  - In Asia, oesophageal diseases, such as Barrett's oesophagus and oesophageal
      carcinoma, have traditionally been less common than in America and Europe. In
      recent years, however, the number of reported cases of these conditions in Japan
      has increased. Two large prospective studies, the Sendai Barrett's Esophagus
      Study (S-BEST) and the Far East Study (FEST), on the geographic prevalence of
      Barrett's oesophagus, have recently investigated the epidemiology of Barrett's
      oesophagus in Japan. Results from both studies showed that overall prevalence of
      the condition is lower than in the West: 0.9-1.2% in Japan compared with 1-4% in
      Europe and 5-12% in USA. Similar to the situation in the West, the condition was
      shown to be most prevalent in elderly male patients and least prevalent in
      patients with Helicobacter pylori. Adenocarcinoma of the oesophagus is still rare
      in this region, although there has been an increase in the annual death rate from
      3.7 (1960) to 6.9 (1995) per 100,000 population. Risk factors for oesophageal
      carcinoma include a strong association with the prevalence of gastro-oesophageal
      reflux disease (GERD). With the increasing prevalence of GERD in the Japanese
      population, continued surveillance of changes in the epidemiology of columnar
      lined oesophagus (a precursor of Barrett's oesophagus), Barrett's oesophagus and
      adenocarcinoma of the oesophagus is strongly recommended.

PMID- 15575875
TI  - Lancefield group C Streptococcus dysgalactiae infection responsible for fish
      mortalities in Japan.
AB  - A Lancefield serological group C Streptococcus sp. was isolated from cultured
      amberjack, Seriola dumerili Risso, and yellowtail, Seriola quinqueradiata
      Temminck and Schlegel, immunized with Lactococcus garvieae commercial vaccines in
      Japan. The isolated bacteria were Gram-positive cocci, auto-aggregating in
      saline, morphologically long chains in growth medium, catalase negative and alpha
      haemolytic on blood agar. An almost complete gene sequence of the 16S rDNA of two
      isolates was determined and compared with that of bacterial strains in the
      database. The isolates were identified as Streptococcus dysgalactiae based on the
      results of the 16S rDNA sequence, the bacteriological properties and the
      Lancefield serological grouping. Oligonucleotide primers specifically designed
      for the 16S-23S rDNA intergenic spacer region of S. dysgalactiae amplified a gene
      from all the fish isolates, as well as the type strains alpha-haemolytic S.
      dysgalactiae subsp. dysgalactiae ATCC430738 and beta-haemolytic S. dysgalactiae
      subsp. equisimilis ATCC35666, but not those of S. equi ATCC33398, Lactococcus
      garvieae ATCC43921 and L. garvieae KG9408. The severe necrotic lesions of the
      caudal peduncle seen in experimentally infected fish were similar to those seen
      in naturally infected fish.

PMID- 15575876
TI  - Purification and characterization of a new reovirus from the Chinese mitten crab,
      Eriocheir sinensis.
AB  - A new reovirus was recently isolated from a freshwater crab, the Chinese mitten
      crab, Eriocheir sinensis, in China. The complete viral particles are 55 nm in
      diameter, icosahedral, non-enveloped and have a mean buoyant density of 1.39 g
      cm(-3) in CsCl gradient. The viral genome is composed of 12 pieces of dsRNA with
      an electrophoretic pattern of 3/4/2/3. This virus infects connective tissue of
      the gills, gut and hepatopancreas. Partial cDNA cloning and sequence analysis
      showed that the RNA-dependent RNA polymerase is located in the first RNA segment.
      From its biochemical, ultrastructural and physicochemical properties, this virus
      is quite different from the genus Aquareovirus (Reoviridae). It may represent a
      new genus of Reoviridae, different from the other crab reoviruses, P and W(2).

PMID- 15575877
TI  - A systemic iridoviral disease in mullet, Mugil cephalus L., and tiger grouper,
      Epinephelus fuscoguttatus Forsskal: a first report and study.
AB  - A systemic iridoviral disease associated with high mortality was initially
      recognized in cultured mullet, Mugil cephalus L., and tiger grouper, Epinephelus
      fuscoguttatus Forsskal, by histopathology and transmission electron microscopy.
      Polymerase chain reaction was performed on tissues and viral isolates, using four
      published primer sets developed for the Red Sea bream iridovirus (RSIV). An
      indirect fluorescent antibody test was also performed on virus-infected ATCC
      gruntfin (GF) and seabass, Lates calcarifer Bloch, (SB) cells using a monoclonal
      antibody, RSIV M10. Our results suggested that the mullet and tiger grouper
      iridovirus bears genetic and antigenic similarities to RSIV.

PMID- 15575878
TI  - The effect of light on the settlement of the salmon louse, Lepeophtheirus
      salmonis, on Atlantic salmon, Salmo salar L.
AB  - The salmon louse, Lepeophtheirus salmonis, is an ectoparasitic copepod that
      infests both wild and farmed salmonid fish. Salmon lice are a major disease
      problem in the farming of Atlantic salmon, Salmo salar L., and the possibility of
      salmon lice playing a role in the decline of wild anadromous stocks has also been
      raised. Lepeophtheirus salmonis can detect a range of stimuli (pressure/moving
      water, chemicals and light) in the external environment. However, the response
      thresholds to various stimuli, and the spatial and temporal scales over which
      they operate in the context of host location, are largely unknown. In this
      context, we attempted to determine whether salmon lice copepodids settle onto
      hosts more effectively, or at different locations on the fish's body, under
      different qualities of light. Lice settlement trials were conducted under three
      lighting conditions; L1: unpolarized under ultraviolet A (UVA)-through visible;
      L2: unpolarized without UVA (control); L3: 100% linearly polarized without UVA. A
      dark control was also conducted. No statistically significant difference in lice
      settlement was found. While changes in light intensity are involved in host
      detection at spatial scales on the order of metres, the results presented here
      suggest that it is not the primary sensory modality underlying host location at
      smaller spatial scales (cm to mm).

PMID- 15575879
TI  - Gill histopathology of wild marine fish in Tasmania: potential interactions with
      gill health of cultured Atlantic salmon, Salmo salar L.
AB  - This study surveyed conditions in the gills of wild marine fish in Tasmania to
      determine potential interactions between wild and cultured fish. Wild marine fish
      of 12 species were captured from three Atlantic salmon farm sites and three
      reference sites around Tasmania. The survey concentrated on three species, red
      cod, Pseudophycis bachus, sand flathead, Platycephalus bassensis, and jack
      mackerel, Trachurus declivus. Seventy-six per cent of salmon pens contained wild
      fish species. The number of species found in a pen ranged from one to nine and
      the number of individuals ranged from one to 23. Trichodinids were prevalent and
      occurred on seven of the 13 species examined. Trichodina occurred on the gills of
      all but one specimen of red cod. Monogenean gill flukes were observed on all
      three major species sampled and were abundant on sand flathead. Other parasites
      and conditions observed in the survey included metacercariae of digenean
      trematodes, epitheliocystis and cysts of unknown origin. Infestations of
      trichodinids on red cod and monogenean gill flukes on sand flathead were
      significantly more intense at farm sites than at reference sites. Atlantic salmon
      sampled at the same time from the farms were only affected by amoebic gill
      disease and isopods.

PMID- 15575880
TI  - Characterization of two membrane-associated protease genes obtained from
      screening out-membrane protein genes of Flavobacterium columnare G4.
AB  - In order to identify genes encoding the outer membrane proteins (OMPs) of the
      myxobacter Flavobacterium columnare G(4), the expression library of the bacterium
      was screened by using rabbit antisera developed against its OMPs. Positive
      colonies of Escherichia coli M15 containing fragments encoding the bacterial OMPs
      were selected for cloning the relevant genes by genomic walking methods. Two
      genes encoding a membrane-associated zinc metalloprotease and prolyl
      oligopeptidase are reported in this paper. The membrane-associated zinc
      metalloprotease gene (map) is 1800 bp in length, coding for 449 amino acids (aa).
      Despite the presence of a conserved motif HEXXH for all metalloproteases, the
      special HEXXH approximately 32 aa approximately E motif of the F. columnare G(4)
      Map and its low level of identity with other reported zinc-containing
      metalloproteases may imply that the membrane-associated zinc metalloprotease of
      F. columnare G(4) represents a new family of zincins. The gene encoding prolyl
      oligopeptidase (Pop), a serine proteinase, is 2352 bp in length, coding for 649
      aa. Sequence homology analysis revealed that the Pop is also novel as it has <
      50% identity with other reported prolyl oligopeptidase family proteins. The
      present study represents the first to employ anti-fish bacterial OMP sera to
      screen genes of membrane-associated proteases of fish pathogenic bacteria, and to
      provide necessary information for the examination of the role of the two genes in
      the infection and pathogenesis of F. columnare.

PMID- 15575881
TI  - A novel 'skinny pot-belly' disease in Asian seabass fry, Lates calcarifer
      (Bloch).

PMID- 15575882
TI  - Evolution of the vertebrate jaw: comparative embryology and molecular
      developmental biology reveal the factors behind evolutionary novelty.
AB  - It is generally believed that the jaw arose through the simple transformation of
      an ancestral rostral gill arch. The gnathostome jaw differentiates from Hox-free
      crest cells in the mandibular arch, and this is also apparent in the lamprey. The
      basic Hox code, including the Hox-free default state in the mandibular arch, may
      have been present in the common ancestor, and jaw patterning appears to have been
      secondarily constructed in the gnathostomes. The distribution of the cephalic
      neural crest cells is similar in the early pharyngula of gnathostomes and
      lampreys, but different cell subsets form the oral apparatus in each group
      through epithelial-mesenchymal interactions: and this heterotopy is likely to
      have been an important evolutionary change that permitted jaw differentiation.
      This theory implies that the premandibular crest cells differentiate into the
      upper lip, or the dorsal subdivision of the oral apparatus in the lamprey,
      whereas the equivalent cell population forms the trabecula of the skull base in
      gnathostomes. Because the gnathostome oral apparatus is derived exclusively from
      the mandibular arch, the concepts 'oral' and 'mandibular' must be dissociated.
      The 'lamprey trabecula' develops from mandibular mesoderm, and is not homologous
      with the gnathostome trabecula, which develops from premandibular crest cells.
      Thus the jaw evolved as an evolutionary novelty through tissue rearrangements and
      topographical changes in tissue interactions.

PMID- 15575883
TI  - Chronic systemic hypoxia causes intra-retinal angiogenesis.
AB  - Retinal hypoxia occurs in many conditions that cause vascular disease in the eye
      and is an important stimulus to new vessel formation. However, the adult retina
      can also become hypoxic when there is systemic hypoxaemia such as occurs in
      chronic lung diseases, congenital cardiac disease and residence at high altitude.
      Little is known about the adaptive responses of the retinal vasculature in such
      circumstances. Previous research in the retinopathy of prematurity model may not
      apply to the adult tissue given the different mechanisms controlling angiogenesis
      in developing and mature circulations. We tested the hypothesis that chronic
      systemic hypoxia leads to angiogenesis in the adult retinal circulation, in the
      absence of pre-existing vascular disease. Adult male Sprague-Dawley rats (n=9)
      were exposed to a fraction of inspired oxygen of 0.10 for 2 weeks while control
      animals (n=10) were exposed to room air. Stereological techniques were used to
      quantify the vascular volume, endothelial surface area and the total number of
      branch points of all blood vessels in the superficial retinal vascular plexus.
      The mean volume and endothelial surface area of these vessels were significantly
      greater in the hypoxic than in the control group. The mean number of blood vessel
      branch points was also significantly greater in the hypoxic group. Our findings
      demonstrate that chronic systemic hypoxia, in the absence of other pathological
      processes, causes angiogenesis in the adult rat retina and provide an in vivo
      model for investigating this important process in the adult retina, in particular
      pathways specific to this tissue.

PMID- 15575884
TI  - Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a
      species comparison.
AB  - The nuclei pulposi of the intervertebral discs (IVDs) contain a mixed population
      of cell types at various stages of maturation. This tissue is formed either by or
      with the help of cells from the embryonic notochord, which appear to be replaced
      during development by a population of chondrocyte-like cells of uncertain origin.
      However, this transition occurs at widely varying times, depending upon the
      species--or even breed--of the animal being examined. There is considerable
      debate among spine researchers as to whether the presence of these residual
      notochordal cells has a significant impact upon IVD degeneration models, and thus
      which models may best represent the human condition. The present study examines
      several different species commonly used in lumbar spine investigations to explore
      the variability of notochordal cells in the IVD.

PMID- 15575885
TI  - Communication between paired chondrocytes in the superficial zone of articular
      cartilage.
AB  - The regeneration and repair of cartilage damaged by injury or disease, a major
      goal of orthopaedic science, depends on understanding the structure and function
      of both the extracellular matrix and the chondrocytes. In this study, we explored
      the in situ organization and potential interactions between chondrocytes in the
      superficial zone of adult rabbit articular cartilage. Some chondrocytes in this
      zone were observed close together and appeared to be paired whereas others were
      solitary. The shared surfaces of a chondrocyte pair were separated by a narrow
      plate of extracellular matrix, into which extended small cytoplasmic projections
      from both cells. Furthermore, the spatial distribution of major cellular
      landmarks, such as the nucleus and centrosome as well as some intracellular
      proteins such as connexin-43, tended to be mirrored about this matrix plate.
      Fluorescence recovery after photobleaching revealed the fluorescent dye calcein
      AM dye can pass between paired cells, and that the passage of this dye can be
      inhibited by the gap junction blocker octanol. These results illustrate that
      rapid cellular communication is possible between cells in the superficial layer
      of adult articular cartilage, which challenges the current thinking that these
      chondrocytes function in isolation.

PMID- 15575886
TI  - Gender-specific distribution of glycosaminoglycans during cartilage
      mineralization of human thyroid cartilage.
AB  - The role of glycosaminoglycans (GAG) in the process of cartilage mineralization,
      especially in the hypertrophic zone of growth plates, is not yet fully
      understood. Human thyroid cartilage can serve as a model to observe matrix
      changes associated with cartilage mineralization because the processes follow a
      distinct route, progress very slowly and show sexual differences. Histochemical
      staining for low sulphated GAG (chondroitin-4- and -6-sulphates) was decreased in
      the interterritorial matrix of thyroid cartilage starting at the beginning of the
      fifth decade, but not in the pericellular or territorial matrix of chondrocytes.
      Because cartilage mineralization progressed in the interterritorial matrix it
      seems likely that a decreasing content of chondroitin-4- and -6-sulphates is
      involved in the mineralization process. This hypothesis is supported by the
      observation that immunostaining for chondroitin-4- and -6-sulphates was weaker in
      mineralized cartilage areas than in unmineralized areas, whereas there was no
      difference in staining for keratan sulphate. In all life decades, female thyroid
      cartilages contained more chondrocytes with a territorial rim of chondroitin-4-
      and -6-sulphates probably preventing cartilage mineralization compared with age
      matched male specimens. Taken together, the characteristic distribution pattern
      of chondroitin-4- and -6-sulphates being more concentrated in female than in male
      thyroid cartilages provided evidence that these macromolecules decrease in
      cartilage mineralization.

PMID- 15575887
TI  - Actin filament organization in aligned prefusion myoblasts.
AB  - The organization of the actin cytoskeleton in prefusion aligning myoblasts is
      likely to be important for their shape and interaction. We investigated actin
      filament organization and polarity by transmission electron microscopy (TEM) in
      these cells. About 84% of the filaments counted were either found in a
      subplasmalemma sheet up to 0.5 microm thick that was aligned with the long axis
      of the cell, or in protrusions. The remaining filaments were found in the
      cytoplasm, where they were randomly orientated and not organized into bundles.
      The polarity of the subplasmalemma filaments changed progressively from one end
      of the cell to the other. At the ends of the cells and in protrusions, the
      majority of filaments were organized such that their barbed ends faced the tip of
      the protrusion. We did not find any actin filament bundles or stress fibres in
      these cells. Time-lapse phase microscopy demonstrated that aligned cells were
      still actively migrating at the time of our TEM observations, and their direction
      of movement was restricted to the long axis of the cell group. The ability of
      these cells to locomote actively in the absence of actin filament bundles
      suggests that in these cells the subplasmalemma actin sheet contributes not only
      to cell shape but also to cell locomotion.

PMID- 15575888
TI  - The expression patterns of mRNA-encoding stem cell factor, internal stem cell
      factor and c-kit in the prepubertal and adult porcine ovary.
AB  - The receptor, c-kit, and its ligand, stem cell factor (SCF), are important
      regulators of ovarian follicle growth and development. The aim of this study was
      to identify the sites of expression of mRNA for c-kit and SCF in prepubertal and
      mature (pregnant and non-pregnant) animals. Ovaries were recovered from
      prepubertal animals, non-pregnant sows and five sows at approximately 3 months of
      gestation. Ovine SCF and c-kit DNA were cloned into plasmid vectors to produce
      RNA probes. Expression of mRNA encoding SCF and c-kit were detected via in situ
      hybridization. Both mRNA were detected throughout ovaries from all animals. This
      study provides evidence that the growth-factor complex is required throughout
      follicle development, and also for continued maintenance of the corpus luteum
      (CL) in the mature animal. SCF mRNA was localized to the granulosa cell layer and
      was also extensively expressed in endothelial tissue and throughout the CL. c-kit
      mRNA was detected in the theca layer, oocytes and also in CL. In conclusion,
      expression of SCF and c-kit mRNA in granulosa and theca cells, respectively,
      indicate an important interaction between somatic cells throughout follicle
      development and that in the mature animal, SCF and c-kit potentially have a role
      in maintaining progesterone secretion by the CL. The observations of continued
      expression of SCF and c-kit throughout development suggest that there may be
      differences in the role of this receptor-ligand complex between large mono- vs.
      poly ovulatory species, such as the pig.

PMID- 15575890
TI  - Unilateral vasectomy in rabbits.

PMID- 15575889
TI  - Evaluation of cyclin D1 expression and its subcellular distribution in mouse
      tissues.
AB  - Cyclin D1 is a key cell-cycle regulatory protein required for the cell to
      progress through G1 to S phase. We have shown by Western blot analysis that
      cyclin D1 has a wide distribution in adult mouse tissues, with its level of
      expression being tissue-dependent. Immunohistochemistry has also shown that
      cyclin D1 may be present in the cytoplasm, in the nucleus or in both these cell
      compartments: cytoplasmic staining was observed in both proliferating cells (e.g.
      kidney, intestine, stomach and salivary gland) and in the non-dividing cells (the
      mature neurons of adult brain), while nuclear staining was seen in the neurons of
      the embryonic nervous system. Immunoelectron microscopy results indicate that, in
      tissues where cyclin D1 is present in both compartments (e.g. intestinal
      enterocytes), it may move via nuclear pores from the nucleus to the cytoplasm,
      and vice versa. The findings as a whole suggest that cyclin D1 may play multiple
      roles within specific tissues, probably by interacting with different substrates,
      and that its transit between nuclear and cytoplasmic compartments may help
      maintain cell homeostasis.

PMID- 15575891
TI  - Another cause for the same old problem.

PMID- 15575892
TI  - Transplantation at any price?

PMID- 15575893
TI  - Should we be performing pancreas transplants?

PMID- 15575894
TI  - Reminiscences of Sir Peter Medawar: in hope of antigen-specific transplantation
      tolerance.
AB  - Peter Medawar's career in medical research (he always described himself as a
      medical research scientist) began as a student of zoology in Oxford. He obtained
      a first class degree in 1936, aged 21, and undertook postgraduate studies with
      Florey. His work was anchored in a broad field; he was adept at addressing novel
      questions in the context of prior ideas and knowledge. His earlier interest in
      growth, driven as much by mathematics as biology, gave way to transplantation at
      the beginning of World War II, treatment of burns patients being the driver. He
      interpreted the results of grafting autologous and allogeneic human skin,
      observed clinically and microscopically, as immunological; he identified
      accelerated donor-specific reactions to subsequent grafts as 'second set', and
      described cell (lymphocyte) mediated infiltration of allo- but not auto-grafts
      following initial vascularization, both in the patient context and in
      experimental animals. He became intrigued by the consequences of hematopoietic
      chimerism, from which his landmark discoveries on the induction of
      transplantation tolerance derive. These results, his interpretation and
      dissemination of them, gave hope to transplant surgeons that donor-specific
      transplant tolerance would be achievable. Many immunosuppressive drugs later, we
      are now reapproaching this hope, from various angles.

PMID- 15575895
TI  - Activation of A3 adenosine receptor provides lung protection against ischemia
      reperfusion injury associated with reduction in apoptosis.
AB  - Apoptosis has been described in various models of ischemia-reperfusion (IR)
      injury, including lung transplantation. A3 adenosine receptor (AR) has been
      linked to a variety of apoptotic processes. The effect of A3AR activation on lung
      injury and apoptosis, following IR, has not been reported to date. In a
      spontaneously breathing cat model, in which the left lower lobe of the lung was
      isolated and subjected to 2 h of ischemia and 3 h of reperfusion, we tested the
      effect of IB-MECA, a selective A3AR agonist, on lung apoptosis and injury.
      Significant increase in the extent of apoptosis was observed following lung
      reperfusion. IB-MECA, administered before IR, and before or with reperfusion,
      markedly (p < 0.01) attenuated indices of injury and apoptosis including the
      percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, in
      situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick end-labeling (TUNEL) positive cells, and caspase 3 activity and expression.
      The protective effects of IB-MECA were completely blocked by pretreatment with
      the selective A3AR antagonist MRS-1191. In summary, even when given after the
      onset of ischemia, the A3AR agonist IB-MECA conferred a powerful protection
      against reperfusion lung injury, which was associated with decreased apoptosis.
      This suggests a potentially important role for A3AR in lung IR injury.

PMID- 15575896
TI  - Over-expression of AIF-1 in liver allografts and peripheral blood correlates with
      acute rejection after transplantation in rats.
AB  - Early and accurate detection of acute cellular rejection (ACR) is important in
      the management of liver allograft recipients. We hypothesized that expression of
      allograft inflammatory factor (AIF)-1 would be associated with liver allograft
      rejection as previous studies have shown that a relationship exists between
      kidney and heart transplantation. Indeed using rat orthotopic transplant models
      we found that the expression of allograft inflammatory factor-1 (AIF-1) can be
      detected in both allograft and peripheral blood leukocytes with peak levels
      detected 7 days following liver transplantation. Interestingly, AIF-1 expression
      increased 2-fold in acutely rejecting liver allografts compared to chronically
      accepted livers on days 5, 7 and 10 after transplantation. AIF-1 expression in
      peripheral blood leukocytes was also significantly greater in the rejection model
      than in the acceptance model. Flow cytometric analysis of peripheral blood
      leukocytes demonstrated that AIF-1 was expressed in ED2-positive cells, a marker
      for Kupffer cells. In vitro studies showed that AIF-1 expression in Kupffer cells
      was up-regulated by coculture with Th1 cytokines. However, neither LPS nor
      Escherichia coli (E. coli) administration had an affect on AIF-1 expression.
      These data indicate that high levels of AIF-1 expression reflect aggressive liver
      allograft rejection and suggest a role for monitoring AIF-1 in peripheral blood
      leukocytes as a monitor for increased immunosuppression.

PMID- 15575897
TI  - Complete inhibition of acute humoral rejection using regulated expression of
      membrane-tethered anticoagulants on xenograft endothelium.
AB  - Xenotransplantation promises an unlimited supply of organs for clinical
      transplantation. However, an aggressive humoral immune response continues to
      limit the survival of pig organs after transplantation into primates. Because
      intravascular thrombosis and systemic coagulopathy are prominent features of
      acute humoral xenograft rejection, we hypothesized that expression of
      anticoagulants on xenogeneic vascular endothelium might inhibit the process.
      Hearts from novel transgenic mice, expressing membrane-tethered fusion proteins
      based on human tissue factor pathway inhibitor and hirudin, respectively, were
      transplanted into rats. In contrast to control non-transgenic mouse hearts, which
      were all rejected within 3 days, 100% of the organs from both strains of
      transgenic mice were completely resistant to humoral rejection and survived for
      more than 100 days when T-cell-mediated rejection was inhibited by administration
      of ciclosporin A. These results demonstrate the critical role of coagulation in
      the pathophysiology of acute humoral rejection and the potential for inhibiting
      rejection by targeting the expression of anticoagulants to graft endothelial
      cells. This genetic strategy could be applied in a clinically relevant species
      such as the pig.

PMID- 15575898
TI  - Severe preservation injury induces Il-6/STAT3 activation with lack of cell cycle
      progression after partial liver graft transplantation.
AB  - Partial liver graft transplantation is a surgical advance developed to overcome
      severe donor shortage. Survival of these grafts involves recovery from cold
      ischemia and reperfusion (CIR) injury, immediate regeneration and maintenance of
      function. Here we examined the outcome of partial liver grafts in comparison to
      whole grafts following CIR injury. Lewis rats subjected to orthotopic liver
      transplantation (OLT) with whole grafts preserved in Viaspan were compared to
      rats receiving 50% and 30% grafts. Outcome was analyzed by survival and
      regeneration. Transplantation was associated with 100% survival for all grafts,
      whereas 16 h preservation resulted in 100%, 20% and 0% survival in animals
      receiving whole, 50% and 30% grafts, respectively. CIR induced increased IL-6
      levels in 50% and 30% grafts, and activation of STAT3. Cell cycle progression
      (cyclin D1) and regeneration (BrdU) was initiated in all livers preserved for 1
      or 8 h, but not in partial grafts preserved for 16 h. In conclusion, partial
      grafts recover from CIR injury through similar molecular pathways to whole
      grafts. Partial grafts with severe injury fail to achieve cellular proliferation
      despite the early initiating signals. This failure could be attributed to the
      impaired ability of the parenchyma to respond to initiating signals for
      regeneration.

PMID- 15575899
TI  - Distinct transcriptional changes in donor kidneys upon brain death induction in
      rats: insights in the processes of brain death.
AB  - Brain death affects hormone regulation, inflammatory reactivity and hemodynamic
      stability. In transplant models, donor organs retrieved from brain dead (BD) rats
      suffer from increased rates of primary non-function and lower graft survival. To
      unravel the mechanisms behind brain death we have performed DNA microarray
      studies with kidney-derived RNA from normo- and hypotensive BD rats,
      corresponding with optimal and marginal BD donors, respectively. In kidneys from
      normotensive donors 63 genes were identified as either up- (55) or down-regulated
      (8), while 90 genes were differentially expressed (67 up-regulated) in
      hypotensive BD donor kidneys. Most genes were categorized in different functional
      groups: metabolism/transport (including the down-regulated water channel Aqp-2),
      inflammation/coagulation (containing the largest number (16) of up-regulated
      genes including selectins, Il-6, alpha- and beta-fibrinogen), cell
      division/fibrosis (including KIM-1 involved in tubular regeneration) and
      defense/repair (with the cytoprotective genes HO-1, Hsp70, MnSOD2). Also, genes
      encoding transcription factors (including immediate early genes as Atf-3, Egr-1)
      and proteins involved in signal transduction (Pik3r1) were identified.
      Summarizing, the use of DNA microarrays has clarified parts of the process of
      brain death: Brain-death-induced effects ultimately lead, via activation of
      transcription factors and signal transduction cascades, to differential
      expression of different "effector" genes. Not only deleterious processes such as
      inflammation and fibrosis occur in brain dead donor kidneys but genes involved in
      protection and early repair processes are activated as well. These findings can
      be used to introduce specific cytoprotective interventions in the brain dead
      donor to better maintain or even increase organ viability.

PMID- 15575900
TI  - Mycophenolic acid inhibits platelet-derived growth factor-induced reactive oxygen
      species and mitogen-activated protein kinase activation in rat vascular smooth
      muscle cells.
AB  - Vascular smooth muscle cell (VSMC) proliferation is the major pathologic feature
      associated with chronic allograft nephropathy, and mycophenolic acid (MPA)
      inhibits VSMC proliferation. Since the role of inosine monophosphate
      dehydrogenase (IMPDH)-dependent de novo guanosine synthesis is limited in VSMCs,
      we examined the effects of MPA on platelet-derived growth factor (PDGF)-induced
      cellular ROS and mitogen-activated protein kinases (MAPK) activation in VSMCs.
      Primary cultured rat VSMCs were stimulated with PDGF-BB in the presence or
      absence of MPA. Cell proliferation was assessed by [3H]-thymidine incorporation,
      ROS by flow cytometry and MAPK activation by Western blot analysis. PDGF
      increased cell proliferation, cellular ROS and extracellular-regulated protein
      kinase (ERK) 1/2 and p38 MAPK activation by 3.4-, 1.6-, 3.3- and 3.9-fold,
      respectively. MPA at above 1 muM inhibited PDGF-induced cellular ROS and ERK 1/2
      and p38 MAPK activation, as well as proliferation. Structurally different anti
      oxidants and inhibitor of ERK or p38 MAPK blocked PDGF-induced proliferation.
      Anti-oxidants also inhibited ERK 1/2 and p38 MAPK activation. Exogenous guanosine
      partially recovered the inhibitory effect of MPA on VSMC proliferation. These
      results suggest that MPA may inhibit PDGF-induced VSMC proliferation partially
      through inhibiting cellular ROS, and subsequent ERK 1/2 and p38 MAPK activation
      in addition to inhibiting IMPDH.

PMID- 15575901
TI  - Survival of microencapsulated adult pig islets in mice in spite of an antibody
      response.
AB  - The aim of this study was to assess the capacity of simple alginate capsules to
      protect adult pig islets in a model of xenotransplantation. Adult pig islets were
      microencapsulated in alginate, with either single alginate coats (SAC) or double
      alginate coats (DAC), and transplanted into the streptozotocin-induced diabetic
      B6AF1 mice. Normalization of glucose levels was associated with an improvement of
      the glucose clearance during intravenous glucose tolerance tests. After
      explantation, all mice became hyperglycemic, demonstrating the efficacy of the
      encapsulated pig islets. Explanted capsules were mainly free of fibrotic reaction
      and encapsulated islets were still functional, responding to glucose stimulation
      with a 10-fold increase in insulin secretion. However, a significant decrease in
      the insulin content and insulin responses to glucose was observed for
      encapsulated islets explanted from hyperglycemic mice. An immune response of both
      IgG and IgM subtypes was detectable after transplantation. Interestingly, there
      were more newly formed antibodies in the serum of mice transplanted with SAC
      capsules than in the serum of mice transplanted with DAC capsules. In conclusion,
      alginate capsules can prolong the survival of adult pig islets transplanted into
      diabetic mice for up to 190 days, even in the presence of an antibody response.

PMID- 15575902
TI  - Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in
      kidney transplant patients.
AB  - Anemia and erythrocytosis (PTE) are common after kidney transplantation. We
      sought to determine the influence of sirolimus compared to mycophenolate mofetil
      (MMF) on post-transplant erythropoiesis. A total of 214 patients with recent
      kidney or kidney-pancreas transplants were treated with either sirolimus-based (n
      = 87) or MMF-based (n = 127) therapy. At 12 months, the prevalence of anemia was
      31% with MMF and 57% with sirolimus (p < 0.001). Linear regression was used to
      examine the independent influence of sirolimus on hemoglobin at 12 months,
      controlling for multiple factors including gender and renal function. Sirolimus
      remained a significant correlate of lower hemoglobin in all patients (slope =
      1.060, 95% CI: -1.76 to -0.362, p = 0.003), and in patients without PTE (slope =
      0.671, 95% CI: -1.32 to -0.028, p = 0.041). PTE, defined as a persistent
      hematocrit above 51%, occurred in 19% with MMF and 7% with sirolimus (p = 0.013).
      PTE was examined using logistic regression analysis. Sirolimus use correlated
      negatively with PTE (odds ratio with sirolimus = 0.33, 95% CI: 0.12 to 0.89, p =
      0.028). Our results indicate that, compared to treatment with MMF, treatment of
      kidney or kidney-pancreas recipients with sirolimus is associated with a higher
      prevalence of anemia, lower hemoglobin levels and lower incidence of PTE.

PMID- 15575903
TI  - The case for living kidney sales: rationale, objections and concerns.
AB  - Currently, potential kidney transplant candidates are dying on the waiting list.
      One potential solution would be a regulated system of living kidney sales (with
      safeguards to protect the vendor). Potential objections and practical concerns
      are discussed.

PMID- 15575904
TI  - Mortality assessment for pancreas transplants.
AB  - We determined and compared the mortality of pancreas transplant recipients and of
      patients on the pancreas waiting lists by using United Network for Organ Sharing
      (UNOS) and International Pancreas Transplant Registry (IPTR) data. From January
      1, 1995, through May 31, 2003, a total of 12,478 patients were listed for a
      simultaneous pancreas-kidney (SPK) transplant; 2942 for a pancreas after
      (previous) kidney transplant (PAK); and 1207 for a pancreas transplant alone
      (PTA). In this retrospective observational cohort study, patients with multiple
      listings at different transplant centers and patients who changed transplant
      centers were counted only once. The Social Security Death Master File (SSDMF) and
      the UNOS kidney transplant database were used to update mortality information. By
      univariate analyses, 4-year patient survival rates on the waiting lists (vs. post
      transplant), in the SPK category, were 58.7% (vs. 90.3%); in the PAK category,
      81.7% (vs. 88.3%); and in the PTA category, 87.3% (vs. 90.5%). Up to one-third of
      recipient deaths after post-transplant day 90 were not related to the transplant
      procedure itself. Multivariate analyses showed that the overall mortality in all
      three categories was not increased after transplantation (for SPK recipients
      only, it was significantly decreased). In summary, the mortality for solitary
      pancreas transplant recipients is not higher than for wait-listed patients.

PMID- 15575905
TI  - Kidney transplantation for systemic sclerosis improves survival and may modulate
      disease activity.
AB  - Systemic sclerosis (SS) may lead to sclerodema renal crisis, an unusual cause of
      end-stage renal disease (ESRD) with historically poor hemodialysis outcomes.
      Little information is available on outcomes after kidney transplantation.
      Information from the UNOS registry was obtained on SS patients in the United
      States, listed for kidney transplants between 1985-2002. We compared survival at
      1 and 3 years in patients who received cadaveric transplants with patients who
      remained on the waiting list. Graft survival, cause of graft loss, frequency of
      early graft loss and pre- and post-transplant skin scores were analyzed. Two
      hundred and fifty-eight patients with SS were listed for transplantation.
      Survival was significantly prolonged in patients receiving transplants (p =
      0.005). Graft survival at 1 and 3 years was 68% and 60%. Early graft loss was
      common. Skin scores improved in all four subjects at our center, with an average
      decline of 60.7% (p = 0.024). Kidney transplantation confers a survival benefit
      in ESRD due to SS. Transplantation may be associated with an improvement in
      systemic manifestations of disease. Despite suboptimal graft survival, kidney
      transplant should be considered the treatment of choice in ESRD due to SS.

PMID- 15575906
TI  - The impact of transplantation with deceased donor hepatitis c-positive kidneys on
      survival in wait-listed long-term dialysis patients.
AB  - Whether transplantation of deceased donor kidney allografts from donors with
      antibodies against hepatitis C virus (HCV) confers a survival advantage compared
      with remaining on the kidney transplant waiting list is not yet known. We studied
      38,270 USRDS Medicare beneficiaries awaiting kidney transplantation who presented
      with end-stage renal disease from April 1, 1995 to July 31, 2000. Cox regression
      was used to compare the adjusted hazard ratios for death among recipients of
      kidneys from deceased donors, and donors with antibodies against hepatitis C
      (DHCV+), controlling for demographics and comorbidities. In comparison to staying
      on the waiting list, transplantation from DHCV+ was associated with improved
      survival among all patients (adjusted hazard ratio for death 0.76, 95% CI 0.60,
      0.96). Of patients receiving DHCV+ kidneys, 52% were themselves hepatitis C
      antibody positive (HCV+), so outcomes associated with use of these grafts may
      have particular implications for HCV+ transplant candidates. Recommendations for
      use of DHCV+ kidneys may require analysis of data not currently collected from
      either dialysis or transplant patients. However, transplantation of DHCV+ kidneys
      is associated with improved patient survival compared to remaining wait-listed
      and dialysis dependent.

PMID- 15575907
TI  - Regression of left ventricular hypertrophy after arteriovenous fistula closure in
      renal transplant recipients: a long-term follow-up.
AB  - The long-term effects of hemodialysis arteriovenous fistula (AVF) closure on left
      ventricular (LV) morphology are unknown. Using echocardiography, we prospectively
      studied 17 kidney transplant recipients before, 1, and, 21 months after AVF
      closure (mean fistula flow 1371 +/- 727 mL/min). Eight kidney transplant
      recipients with a patent AVF, matched for age, time after AVF creation, and time
      after transplantation, served as controls. LV mass index (LVMI) decreased from
      139 +/- 44 g/m2 before AVF closure to 127 +/- 45 g/m2 and 117 +/- 40 g/m2 at 1
      and 21 months post-closure, respectively (p < 0.001), but remained unchanged in
      controls. LV hypertrophy prevalence (LVMI > 125 g/m2) decreased from 65% before,
      to 41% early, and 18%, late, after surgery (p = 0.008), mostly from a decrease in
      LV end-diastolic diameter. Consequently, the prevalence of LV concentric
      remodeling (relative wall thickness > 0.45 without hypertrophy) increased from
      12% before, to 35% early, and 65% late, after surgery (p = 0.003). Diastolic
      arterial blood pressure increased from 78 +/- 15 mmHg before, to 85 +/- 13 mmHg
      early, and 85 +/- 10 mmHg late, after surgery (p < 0.015). In conclusion, closure
      of large and/or symptomatic AVF induces long-term regression of LV hypertrophy.
      However, residual concentric remodeling geometry as well as diastolic blood
      pressure increase may blunt the expected beneficial cardiac effects of the
      procedure.

PMID- 15575908
TI  - Pre-transplant inosine monophosphate dehydrogenase activity is associated with
      clinical outcome after renal transplantation.
AB  - Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase
      (IMPDH) activity, is usually administered as a standard dose of 1 g b.i.d. after
      renal transplantation. Because MMF dose reductions are associated with inferior
      outcome, we investigated pre-transplant IMPDH activity, MMF dose reductions and
      outcome. IMPDH activity was determined in isolated peripheral mononuclear cells
      immediately prior to renal transplantation. We observed considerable inter
      individual variability in pre-transplant IMPDH activity (9.35 +/- 4.22
      nmol/mg/h). Thirty of 48 patients (62.5%) with standard MMF dose (1 g b.i.d.) had
      dose reductions within 3 years post-transplant; these patients also had
      significantly lower IMPDH activity. The area under the receiver-operating
      characteristics curve (AUC-ROC) for prediction of dose reduction within 6 months
      post-transplant was 0.75 (95% CI, 0.61-0.89; p < 0.004). IMPDH activity above the
      cut-off value, MMF dose reduction and age of recipient were significant
      contributors for the occurrence of acute rejection in the multivariate logistic
      regression. Patients with high IMPDH activity and MMF dose reduction had the
      highest rejection rate (81.8% vs. 36.4%; p < 0.01). CONCLUSION: Patients with low
      IMPDH activity experienced more complications of MMF therapy. High pre-transplant
      IMPDH activity and MMF dose reductions were associated with rejection.
      Determination of IMPDH activity prior to transplantation may help to improve MMF
      therapy after renal transplantation.

PMID- 15575909
TI  - A prospective randomized study for the treatment of bone loss with vitamin d
      during kidney transplantation in children and adolescents.
AB  - The effect of treatment with alfacalcidol on post-transplantation bone loss in
      children and adolescents was investigated. Of the 63 young patients who received
      renal transplant and were subjected to dual-energy x-ray absorptiometry (DEXA),
      30 patients had low-bone mineral density (BMD) (z-score < or = -1) and were
      enrolled into the study. Their mean age at the time of transplantation was 14.5
      +/- 4.0 years and the mean duration after transplantation was 48 +/- 34 months.
      Patients with low BMD were randomized into two equal homogeneous groups: group 1
      (control) received placebo and group 2 received daily alfacalcidol 0.25 microg by
      mouth. Parameters of bone metabolism (intact parathyroid hormone, serum
      osteocalcin and urinary deoxypyridinoline) and BMD were assessed before and after
      the study period. After 12 months of treatment BMD at the lumber spine decreased
      from -2.2 to -2.5 in group 1 while it increased from -2.1 to -0.6 in group 2 (p <
      0.001). Serum intact parathyroid hormone level decreased significantly in group 2
      (p = 0.042). Apart from transient hypercalcemia in 1 patient in group 2, no other
      significant adverse effects were noted. This study suggested the value of
      alfacalcidol in the treatment of bone loss in young renal transplant recipients.

PMID- 15575910
TI  - Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with
      decreased renal allograft survival.
AB  - To evaluate the association between a regimen of cyclosporine microemulsion (CsA)
      + sirolimus (Rapa) treatment versus CsA and mycophenolate mofetil (MMF) and renal
      allograft survival, we analyzed 23 016 primary recipients reported to the
      Scientific Registry of Transplant Recipients between January 1, 1998 and July 26,
      2003. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard
      models correcting for demographic and clinical covariates were used to estimate
      the relative risks for CsA+Rapa versus CsA+MMF-treated patients reaching study
      endpoints. Subgroup analyses were conducted for recipient ethnicity and donor
      type. CsA+Rapa was associated with significantly lower graft survival (74.6% vs.
      79.3% at 4 years, p = 0.002) and death-censored graft survival (83.7% vs. 87.2%,
      p = 0.003) compared to CsA+MMF. In multivariate analyses, CsA+Rapa was associated
      with a significantly increased risk for graft loss, death-censored graft loss and
      decline in renal function (HR = 1.22, p = 0.002; HR = 1.22, p = 0.018 and HR =
      1.25, p < 0.001, respectively). Similar results were obtained in recipient
      ethnicity and donor type subgroups. In summary, CsA+Rapa was associated with
      significantly worse graft survival and death-censored graft survival compared to
      CsA+MMF, and likely reflects full-dose CsA +Rapa. Outcomes regarding alternative
      strategies of Rapa utilization with reduced CsA, with alternative agents or with
      no calcineurin inhibitor cannot be extrapolated from these data.

PMID- 15575911
TI  - How old is old for transplantation?
AB  - Elderly patients are the fastest growing group requiring renal transplantation.
      This study investigates whether transplantation is worthwhile in the elderly and
      whether there is evidence supporting an age limit for transplantation. One
      thousand ninety-five adults transplanted in Scotland between 1 January 1989 and
      31 December 1999 were followed up to 11 years. Sociodemographic, comorbidity and
      transplant data were obtained from the national databases and patient's notes.
      Patient and graft survival, risk and causes of graft failure and patient death
      were compared between four age groups (18-49, 50-59, 60-64 and >65). All groups
      had similar gender, social deprivation and renal disease distribution. The
      incidence of comorbidity increased with age. The groups had comparable HLA
      matching, but patients aged 18-49 years received transplants from younger donors
      and with shorter cold ischaemic times. Younger patients had more acute rejection
      and less delayed graft function. Older patients had a higher incidence of death
      with functioning graft. Patients over 65 years had an almost dialysis-free
      remaining life, while the graft half-life was significantly shorter than patient
      half-life in the youngest group. Transplantation in elderly recipients is
      worthwhile despite a higher comorbidity. Careful selection rather than a fixed
      age limit should be used to ensure a satisfactory graft and patient survival.

PMID- 15575912
TI  - Percentage of hypochromic red blood cells is an independent risk factor for
      mortality in kidney transplant recipients.
AB  - There are no published studies on the associations between anemia or iron status
      parameters and important long-term outcomes in kidney transplant recipients
      (KTR). We prospectively studied 438 KTR from a large transplant clinic for all
      cause mortality and kidney allograft loss. Hemoglobin and iron status parameters
      (serum iron, transferrin, transferrin saturation, ferritin, percentage of
      hypochromic red blood cells [%HRBC]) were assessed at baseline as were important
      demographic, clinical and laboratory characteristics. The Austrian Dialysis and
      Transplant Registry and the Eurotransplant database were used to ascertain
      immunological and transplantation-related parameters and to ascertain death and
      allograft rejection. Cox proportional hazard models were used for analyses. Over
      7.8 years of follow-up, 129 deaths (29.5%) occurred and 208 grafts (47.5%) were
      lost. From multivariate analyses, we found that anemia (hemoglobin <10g/dL) was
      not associated with mortality or graft loss. Among the iron status parameters,
      only %HRBC was associated with greater all-cause mortality. Patients with HRBC
      >10% had twice the mortality risk (HR: 2.06; 95%CI: 1.12-3.79) compared to
      patients with HRBC <5%. Neither of the iron status parameters were associated
      with allograft rejection. In conclusion, we found that %HRBC was an independent
      risk factor for mortality in KTR, while other iron status parameters or anemia
      were not associated with risk. Larger studies on the association between anemia
      and these outcomes are warranted.

PMID- 15575913
TI  - Histological patterns of polyomavirus nephropathy: correlation with graft outcome
      and viral load.
AB  - Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft
      loss. The diagnosis requires allograft biopsy, but the impact of the histological
      features on diagnosis and outcome has not been described. We studied the
      distribution and extent of PVAN in 90 patients. Viral cytopathic changes, tubular
      atrophy/fibrosis and inflammation were semi-quantitatively scored and classified
      into histological patterns. The histological findings were correlated with
      viruria, viremia and graft survival. PVAN lesions were random, (multi-)focal and
      affected both cortex and medulla. Areas with PVAN coexisted with areas of
      unaffected parenchyma. In 36.5% (15/41) of biopsies with multiple tissue cores,
      discordant findings with PVAN-positive and -negative cores were observed.
      However, all patients with PVAN had decoy cells in urine as well as significant
      viruria and viremia (mean of 2.5 x 10(8) and 2.32 x 10(7) viral copies,
      respectively). Biopsies showing lesser degrees of renal scarring at the time of
      diagnosis were associated with, more likely, resolution of the infection, in
      response to decrease of immunosuppression (p = 0.001). More advanced
      tubulointerstitial atrophy, active inflammation and higher creatinine level at
      diagnosis correlated with worse graft outcome (p = 0.0002, 0.0001 and 0.0006).
      Due to the focal nature of PVAN, correlation of biopsy results with viruria and
      viremia are required for diagnosis.

PMID- 15575914
TI  - Superior long-term results of simultaneous pancreas-kidney transplantation from
      pediatric donors.
AB  - The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation
      has prompted the use of cadaveric organs from pediatric donors. The long-term
      outcome and its impact on overall long-term survival are unknown. A total of 680
      recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation
      from pediatric and adult donors between July 1986 and September 2001 were
      analyzed and compared. Ten-year kidney and pancreas graft survival for SPK
      transplantation from donors aged <18 years (n = 142) were 80% and 72%,
      respectively, compared to 61% pancreas and kidney graft survival from donors > or
      =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post
      transplant, blood glucose, HbA1c and creatinine clearance were significantly
      better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and
      65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1
      +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002,
      respectively). Causes of graft failure for kidney and pancreas transplants were
      similar between the two groups. No statistically significant difference was
      observed in patient survival between recipients from pediatric donors compared to
      adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric
      donors were stratified according to age (3-11 years and 12-17 years) and
      compared, no difference in kidney or pancreas graft survival was observed (kidney
      76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively).
      Pediatric donors represent a valuable source of organs, providing excellent short
      and long-term outcomes. Wide utilization of pediatric organs will substantially
      increase the donor pool.

PMID- 15575915
TI  - Monitoring of adenovirus infection in pediatric transplant recipients by
      quantitative PCR: report of six cases and review of the literature.
AB  - Adenoviral (AdV) infections after transplantation remain a challenge in pediatric
      patients. Qualitative and quantitative PCR offer new approaches to early
      diagnosis and monitoring. However, their role in the management of AdV infections
      in pediatric transplant recipients remains to be determined. We report six
      children with positive qualitative serum-PCR for AdV on routine follow-up after
      transplantation (liver n = 4, hematopoetic stem cells (HSCT) n = 1, combined
      liver and HSCT n = 1). None of these children were symptomatic at the time of
      first detection of AdV. Two patients remained asymptomatic, one developed
      hemorrhagic cystitis and enteritis. Three children with positive PCR developed
      high viral load on quantitative PCR, all developed clinical AdV sepsis with
      further rising virus load. Despite antiviral therapy with cidofovir, these three
      patients died of septic multiorgan failure. Positive qualitative AdV-PCR from
      blood after pediatric transplantation is not necessarily followed by clinical
      disease. In case of positive AdV-PCR, monitoring by serial quantitative PCR is
      useful regarding treatment decision and prevention of fatal disease.

PMID- 15575916
TI  - Polyomavirus nephropathy in pediatric kidney transplant recipients.
AB  - Given the limited information regarding BK virus-associated nephropathy (BKVN) in
      pediatric kidney transplant recipients, we assessed the incidence, risk factors,
      clinical and virologic features of BKVN in pediatric renal transplant recipients
      at a single transplant center by means of a retrospective cohort study.
      Histologically confirmed BKVN developed in 6 of 173 (3.5%) kidney transplant
      recipients at a median of 15 months post-transplant (range: 4-47 months). At a
      median follow-up of 28 months (range: 5-32), all patients had functioning grafts
      with mean creatinine and GFR of 1.9 mg/dL and 58 mL/min/1.73 m2, respectively. At
      the time of diagnosis, all cases had viruria (median 6.1 x 10(6) copies/mL,
      range: 10(5) to 3.9 x 10(8) copies/mL) and viremia (median 21,000 copies/mL,
      range: 10,000-40,000 copies/mL). Recipient seronegativity for BKV was
      significantly associated with the development of BKVN (p = 0.01). BKVN is an
      important cause of late allograft dysfunction and is strongly associated with
      recipient seronegativity in pediatric kidney transplant recipients. Further
      studies to confirm this finding and to define the clinical utility of routine pre
      transplant BKV serologic testing are warranted.

PMID- 15575917
TI  - Analyses of peripheral blood mononuclear cells in operational tolerance after
      pediatric living donor liver transplantation.
AB  - Operational tolerance (graft acceptance in an immunosuppression (IS)-free
      environment) after living-donor liver transplantation (LDLT) could occur by our
      elective protocol in some patients. There is, nevertheless, no reliable parameter
      to monitor patients who may discontinue IS without a risk of rejection. To
      identify such parameters, we systemically phenotyped peripheral blood mononuclear
      cells from operationally tolerant patients. An increase was observed in the
      frequency of CD4+CD25high+ cells, B cells and Vdelta1/Vdelta2 gammadeltaT-cells
      ratio in operationally tolerant patients (Gr-tol; n = 12), compared with those
      from age-matched volunteers (Gr-vol; n = 24) or patients on IS (Gr-IS; n = 19).
      The frequency of NK cells was decreased in Gr-tol, compared with those in Gr-IS
      or Gr-vol. The frequency of NKT cells was decreased after LDLT, compared with
      that in Gr-vol. Although the contribution of those subsets to the tolerant state
      remains elusive, the results may provide important clues for reliable indicators
      of tolerance after LDLT.

PMID- 15575918
TI  - Therapeutic drug monitoring for everolimus in heart transplant recipients based
      on exposure-effect modeling.
AB  - Everolimus, a proliferation signal inhibitor, is an immunosuppressant that
      targets the primary causes of progressive allograft dysfunction, thus improving
      the long-term outcome after heart transplantation. The present study investigated
      whether therapeutic drug monitoring (TDM) of everolimus would benefit heart
      transplant patients. Data from a twelve-month phase III trial comparing
      everolimus (1.5 or 3 mg daily) with azathioprine were used to evaluate everolimus
      pharmacokinetics, exposure-efficacy/safety and TDM prognostic simulations.
      Everolimus trough levels were stable in the first year post-transplant and
      averaged 5.2 +/- 3.8 and 9.4 +/- 6.3 ng/mL in patients treated with 1.5 and 3
      mg/day, respectively. Cyclosporine trough levels were similar in all treatment
      groups. Biopsy-proven acute rejection (BPAR) was reduced with everolimus trough
      levels > or =3 ng/mL. Intravascular ultrasound (IVUS) analysis showed evidence of
      reduced vasculopathy at 12 months with increasing everolimus exposure. Unlike
      cyclosporine, increasing everolimus exposure was not related to a higher rate of
      renal dysfunction. The TDM simulation, which was based on two everolimus dose
      adjustments and an initial starting dose of 1.5 mg/day, showed that the simulated
      BPAR rate (with TDM) was 21% versus 26% in the group with fixed dosing.
      Therefore, TDM in heart transplantation could optimize immunosuppressive efficacy
      and reduce treatment-related toxicity.

PMID- 15575919
TI  - BK nephropathy in kidney transplant recipients treated with a calcineurin
      inhibitor-free immunosuppression regimen.
AB  - Recently, polyomavirus-associated nephropathy (PVAN) has been reported more
      frequently and is emerging as an important cause of renal allograft dysfunction
      and graft loss. Susceptibility appears to be related to the type and intensity of
      pharmacologic immunosuppression but some reports have suggested a link among the
      development of PVAN, the treatment of rejection or maintenance with a tacrolimus
      based immunosuppressive regimen. We report three cases of PVAN in patients who
      never received immunosuppression with calcineurin inhibitors (CNIs). Two patients
      received induction immunosuppression consisting of an IL-2 receptor antagonist
      while 1 received thymoglobulin. These 3 patients were maintained on prednisone,
      sirolimus and mycophenolate mofetil (MMF) and none was treated for rejection. All
      three patients presented with an elevated serum creatinine and demonstrated
      polyomavirus infection on biopsy and by blood PCR. These cases demonstrate that,
      unlike reports linking tacrolimus and PVAN, polyomavirus infection may develop in
      patients maintained on CNI-free immunosuppressive regimens and have not had
      episodes of rejection.

PMID- 15575920
TI  - Pioglitazone in the management of diabetes mellitus after transplantation.
AB  - Type 2 diabetes mellitus is a common problem in patients after solid organ
      transplantation. We studied the safety and efficacy of pioglitazone therapy in
      this setting. Ten patients with diabetes mellitus treated with insulin or
      glyburide after transplantation were studied after the addition of the
      thiazolidinedione pioglitazone. Serum creatinine, HBA1C, total daily insulin
      dose, tacrolimus dose, tacrolimus level and prednisone dose were followed for a
      mean of 242 days and compared to the corresponding values measured before the
      initiation of pioglitazone. The addition of pioglitazone caused no significant
      changes in serum creatinine or mean tacrolimus dose, and caused decreases in
      HBA1C (8.36%+/- 1.5% pre-pioglitazone, 7.08%+/- 1.5% post-pioglitazone, p =
      0.018) and total daily insulin dose (125.1 +/- 28.1 units pre-pioglitazone, 80.6
      +/- 22.8 units post-pioglitazone, p = 0.002). Our preliminary study suggests that
      pioglitazone is a safe and effective oral agent for the management of diabetes
      mellitus after transplantation.

PMID- 15575921
TI  - Conversion from cyclosporine to tacrolimus improves quality-of-life indices,
      renal graft function and cardiovascular risk profile.

PMID- 15575923
TI  - Sublingual immunotherapy: from proven prevention to putative rapid relief of
      allergic symptoms.

PMID- 15575924
TI  - Sublingual immunotherapy for allergic rhinitis: systematic review and meta
      analysis.
AB  - Allergic rhinitis is a common condition which, at its most severe, can
      significantly impair quality of life despite optimal treatment with
      antihistamines and topical nasal corticosteroids. Allergen injection
      immunotherapy significantly reduces symptoms and medication requirements in
      allergic rhinitis but its use is limited by the possibility of severe systemic
      reactions. There has therefore been considerable interest in alternative routes
      for delivery of allergen immunotherapy, particularly the sublingual route. The
      objective was to evaluate the efficacy of sublingual immunotherapy (SLIT),
      compared with placebo, for reductions in symptoms and medication requirements.
      The Cochrane Controlled Clinical Trials Register, MEDLINE (1966-2002), EMBASE
      (1974-2002) and Scisearch were searched, up to September 2002, using the terms
      (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). All
      studies identified by the searches were assessed by the reviewers to identify
      Randomized Controlled Trials involving participants with symptoms of allergic
      rhinitis and proven allergen sensitivity, treated with SLIT or corresponding
      placebo. Data from identified studies was abstracted onto a standard extraction
      sheet and subsequently entered into RevMan 4.1. Analysis was performed by the
      method of standardized mean differences (SMD) using a random effects model. P
      values < 0.05 were considered statistically significant. Subgroup analyses were
      performed according to the type of allergen administered, the age of participants
      and the duration of treatment. Twenty-two trials involving 979 patients, were
      included. There were six trials of SLIT for house dust mite allergy, five for
      grass pollen, five for parietaria, two for olive and one each for, ragweed, cat,
      tree and cupressus. Five studies enrolled exclusively children. Seventeen studies
      administered the allergen by sublingual drops subsequently swallowed, three by
      drops subsequently spat out and two by sublingual tablets. Eight studies involved
      treatment for less than 6 months, 10 studies for 6-12 months and four studies for
      greater than 12 months. All included studies were double-blind placebo-controlled
      trials of parallell group design. Concealment of treatment allocation was
      considered adequate in all studies and the use of identical placebo preparations
      was almost universal. There was significant heterogeneity, most likely due to
      widely differing scoring systems between studies, for most comparisons. Overall
      there was a significant reduction in both symptoms (SMD -0.42, 95% confidence
      interval -0.69 to -0.15; P = 0.002) and medication requirements [SMD -0.43 (
      0.63, -0.23); P = 0.00003] following immunotherapy. Subgroup analyses failed to
      identify a disproportionate benefit of treatment according to the allergen
      administered. There was no significant reduction in symptoms and medication
      scores in those studies involving only children but total numbers of participants
      was too small to make this a reliable conclusion. Increasing duration of
      treatment does not clearly increase efficacy. The total dose of allergen
      administered may be important but insufficient data was available to analyse this
      factor.

PMID- 15575925
TI  - The rise of the phoenix: the expanding role of the eosinophil in health and
      disease.
AB  - We have entered a new phase in the evolution of our understanding of the role of
      the eosinophil with a greater appreciation of novel potential functions that may
      be ascribed to this enigmatic cell type. This review not only provides an update
      to our current understanding of the various immunobiological roles for the
      eosinophil, but also attracts attention to some novel observations predicting
      functions beyond its putative effector role. These observations include the
      intriguing possibility that the eosinophil may possess the capacity to regulate
      the immune and inflammatory responses in diseases such as asthma.

PMID- 15575926
TI  - Inflammatory events in severe acute asthma.
AB  - Severe acute asthma can be induced by different triggers, allergens, irritants,
      viruses, etc., which induce inflammation and provoke acute bronchoconstriction.
      Inflammatory cells, such as activated eosinophils and neutrophils identified in
      sputum and bronchial lavages (BL) in severe acute asthma from children and adults
      are associated with increased levels of IL-5, IL-8, and of proinflammatory
      mediators. Viruses, but also endotoxin or allergen exposure, are able to recruit
      neutrophils, via an IL-8 production by activated macrophages or epithelial cells.
      Together, these inflammatory mediators are responsible for the diffuse bronchial
      inflammation, which involve large and small airways. Activated T cells may also
      be related to the pathogenesis of severe asthma. An aberrant CD8+ T lymphocyte
      response in bronchi, with a cytotoxic activity has been associated with fatal
      asthma. Moreover, the persistence of inflammatory cells in bronchi, particularly
      neutrophils, which respond poorly to corticosteroids, could be in part
      responsible for the epithelial damage, the extensive mucus plugging, and the
      abnormalities of epithelial and endothelial permeability which are associated
      with severe acute asthma. Further studies are necessary to better identify the
      implication of this increased bronchial permeability in the persistence of high
      levels of airway resistance, particularly in patients with status asthmaticus.

PMID- 15575927
TI  - Does atopy protect against enteric infections?
AB  - Allergic sensitization to inhaled allergens and foods is common and is linked to
      the development of asthma, allergic rhinitis and eczema. In view of the morbidity
      associated with these diseases it is not clear why the genetic predisposition to
      atopy is so common. Children who are atopic are less likely to develop oral
      tolerance to ingested foods and as a result are more likely to have
      manifestations of food allergy including wheezing, skin rashes and
      gastrointestinal symptoms. Oral tolerance also develops to micro-organisms in the
      gastrointestinal tract. Children who are atopic may be protected against enteric
      infections in early childhood because they are less likely to be tolerant of
      these organisms. This may explain why individuals who are atopic are less likely
      to have evidence of previous infection with hepatitis A and other enteric
      organisms although they are just as likely to have been infected with respiratory
      pathogens.

PMID- 15575928
TI  - Characterization of the T-cell epitopes of a major peanut allergen, Ara h 2.
AB  - BACKGROUND: The development of safe and effective immunotherapy for peanut
      allergy has been complicated by the high anaphylactic potential of native peanut
      extracts. We sought to map the T-cell epitopes of the major peanut allergen, Ara
      h 2 in order to develop T-cell targeted vaccines. METHODS: A panel of eight
      peanut-specific CD4+ T-cell lines (TCL) was derived from eight peanut-allergic
      subjects and proliferative and cytokine responses to stimulation with a set of
      overlapping 20-mer peptides representing the entire sequence of Ara h 2
      determined. Proliferation was assessed in 72 h assays via tritiated thymidine
      incorporation, while interleukin (IL)-5 and interferon (IFN)-gamma production
      were assessed via sandwich enzyme-linked immunosorbent assay (ELISA) of cell
      culture supernatants. RESULTS: Eight of the 17 Ara h 2 peptides were recognized
      by one or more subjects, with the two peptides showing highest reactivity [Ara h
      2 (19-38) and Ara h 2 (73-92)] being recognized by three subjects each. Adjoining
      peptides Ara h 2 (28-47) and Ara h 2 (100-119) induced proliferative responses in
      two subjects. Each of these peptides was associated with a Th2-type cytokine
      response. CONCLUSION: Two highly immunogenic T-cell reactive regions of Ara h 2
      have been identified, Ara h 2 (19-47) and Ara h 2 (73-119), providing scope for
      the development of safe forms of immunotherapy for peanut allergy.

PMID- 15575929
TI  - Allergenic composition of the mite Suidasia medanensis and cross-reactivity with
      Blomia tropicalis.
AB  - BACKGROUND: Mites of the genus Suidasia are commonly found in house dust and may
      play an allergenic role in exposed populations. However, the allergenic potential
      and clinical impact of this genus has not been well established. The main
      objective of this project was to evaluate the allergenic role of the mite
      Suidasia medanensis. METHODS: An extract of S. medanensis was prepared and the
      allergen composition determined by immunoblot. Specific IgE antibody levels to S.
      medanensis and Blomia tropicalis were evaluated by radioallergosorbent (RAST) in
      the sera of 97 allergic asthmatic patients and 50 nonallergic subjects. Cross
      reactivity between S. medanensis and the mite species B. tropicalis and
      Dermatophagoides farinae was investigated by RAST and immunoblot inhibitions.
      RESULTS: Seventy-one asthmatic patients sera (73.2%) had positive IgE reactivity
      to S. medanensis; 14 allergens with molecular weights ranging from 7.5 to 105 kDa
      were detected. The most frequently detected had molecular weights of 30-31
      (54.8%), 24.5 (42%), 21 (38.7%), 47 (35%) and 58 kDa (35.5%). Blomia tropicalis
      extract inhibited IgE binding to nine of these identified allergens. Four B.
      tropicalis allergens were inhibited by S. medanensis extract. RAST inhibition
      results demonstrated a high degree of inhibition by B. tropicalis (87.2%) and D.
      farinae (90.9%) than by S. medanensis (32%). CONCLUSIONS: Sensitization to S.
      medanensis is common in asthmatic allergy patients in Cartagena. An important
      degree of cross-reactivity was established between S. medanensis and B.
      tropicalis, and D. farinae.

PMID- 15575930
TI  - Mustard allergy confirmed by double-blind placebo-controlled food challenges:
      clinical features and cross-reactivity with mugwort pollen and plant-derived
      foods.
AB  - BACKGROUND: Mustard IgE-mediated allergy is supposed to be a rare cause of food
      allergy, and its clinical features and cross-reactivities have not been fully
      elucidated. METHODS: A prospective study was carried out, recruiting mustard
      allergic patients, and paired control subjects. A clinical questionnaire was
      administered, and skin-prick tests (SPT) with panels of aeroallergens and foods,
      serum extraction for in vitro tests and double-blind placebo-controlled food
      challenges (DBPCFC) were performed. RESULTS: Thirty-eight mainly adult patients,
      with 10.5% reporting systemic anaphylaxis, were included in the study [age (mean
      +/- SD): 21.9 +/- 8.6 years]. DBPCFC were performed in 24 patients, being
      positive in 14 cases (58.3%). Patients with positive outcome showed significantly
      greater mustard SPT than those with negative outcome (8.2 +/- 3.7 vs 5.3 +/- 2.4
      mm, P <0.05), and the receiver-operating characteristic (ROC) curve analysis
      yielded a cut-off value for mustard commercial SPT of 8 mm, with a specificity of
      90% (95% CI, 55.5-98.3), and a sensitivity of 50% (95% CI, 23.1-76.9). A
      significant association between mustard hypersensitivity and mugwort pollen
      sensitization was found (97.4% of patients), with partial cross-reactivity
      demonstrated by UniCAP System inhibition assays. All patients showed
      sensitization to other members of Brassicaceae family, and cross-reactivity among
      them was also confirmed. Moreover, significant associations with nut (97.4%),
      leguminous (94.7%), corn (78.9%), and Rosaceae fruit (89.5%) sensitizations were
      also shown. Around 40% of these food sensitizations were symptomatic, including
      food-dependent exercise-induced anaphylaxis in six patients. CONCLUSIONS: Mustard
      allergy is a not-uncommon disorder that can induce severe reactions. Significant
      associations with mugwort pollinosis and several plant-derived food allergies are
      demonstrated, suggesting a new mustard-mugwort allergy syndrome. A relationship
      between this syndrome and food-dependent exercise-induced anaphylaxis is also
      reported.

PMID- 15575931
TI  - The links between allergen skin test sensitivity, airway responsiveness and
      airway response to allergen.
AB  - BACKGROUND: The allergen-induced early asthmatic response [provocation
      concentration (PC)20, the concentration causing a 20% forced expiratory volume in
      1 s (FEV)1 fall] depends on the level of IgE sensitivity and the degree of
      nonallergic airway hyperresponsiveness (AHR) and can be predicted from histamine
      PC20 and allergen skin test endpoint. OBJECTIVES: We examined the relationships
      between allergen PC20, methacholine PC20, and allergen skin test endpoint and
      assessed the accuracy of both the histamine PC20-based prediction of allergen
      PC20 (using methacholine) and a new methacholine PC20-based prediction equation.
      METHODS: From 158 allergen challenges, the allergen PC20, the methacholine PC20,
      and the skin test endpoint were recorded and relationships between these three
      were sought. We compared the measured allergen PC20 to that predicted from the
      previous histamine PC20-based and the new methacholine-based formulae. RESULTS:
      In single regressions, allergen PC20 correlated with both methacholine PC20
      (r=0.25, P=0.0015) and skin test endpoint (r=0.52, P <0.00005). The relationship
      was improved by multiple regression of log-allergen PC20vs. log-methacholine PC20
      and log-endpoint (r=0.61, P <0.00005). The histamine-based formula predicted
      allergen PC20 to within 2 doubling concentrations in 80% and within 3 in 92%. The
      new methacholine-based formula to within 2 and 3 concentrations in 81% and 94%,
      respectively; only nine of 158 subjects were outside the 3 concentrations.
      CONCLUSIONS: We have confirmed the dependence of the allergen-induced early
      asthmatic response upon the level of allergic sensitivity and the degree of AHR,
      the latter as assessed by methacholine challenge. The allergen PC20 can be
      predicted to within 3 doubling concentrations in 94% of cases.

PMID- 15575932
TI  - Urinary inflammatory mediators and inhalation of hypertonic saline in children.
AB  - BACKGROUND: The inflammatory mechanisms of hypertonic saline-induced
      bronchoconstriction are not well understood. METHODS: Seventeen asthmatics with
      (n=11) and without bronchial hyperresponsiveness (BHR) (n=6) and 18 randomly
      selected nonatopic nonasthmatic controls without BHR were evaluated by urine
      samples collected before and 1 h after hypertonic saline provocation test.
      Histamine, 11beta-PGF2alpha, and LTE4 were analysed by enzyme immunoassay (EIA)
      and eosinophil protein X (EPX) by radioimmunoassay (RIA). RESULTS: The levels of
      leukotriene E4 (LTE4) increased significantly after the challenge tests, both in
      the asthmatics (median: 354 pg/mg pre-challenge vs. 628 pg/mg post-challenge;
      P=0.05) and in the controls (median: 294 pg/mg pre-challenge vs. 460 pg/mg post
      challenge; P <0.01). The levels of histamine also increased significantly in the
      latter (median: 299 micromol/mg pre-challenge vs. 569 micromol/mg post-challenge;
      P=0.03). However, the levels of 11beta-PGF2alpha and EPX did not change
      significantly after the challenge tests either in the asthmatics or in the
      controls. CONCLUSIONS: The inhalation of hypertonic saline increased urinary
      excretion of LTE4 both in the asthmatics and in the controls. The slight increase
      of leukotrienes was enough to induce airway obstruction in some of the
      asthmatics, because of the hyperresponsiveness in their airways.

PMID- 15575933
TI  - Differential effects of fluticasone and montelukast on allergen-induced asthma.
AB  - Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen
      are induced by the local release of a series of bronchoconstrictor mediators,
      including leukotrienes and histamine. Both anti-leukotrienes and other anti
      asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR
      and LAR. The aim of the present study was to directly compare the effects of
      regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once
      daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP)
      250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen
      challenge. Patients with a documented EAR and LAR at a screening visit were
      randomized to these treatments, or placebo, in a double-blind, double-dummy,
      crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was
      given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was
      17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for
      Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo
      treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs
      placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after
      allergen challenge during FP-treatment compared with Mont (P <0.05). Both
      montelukast and fluticasone reduced the relative amount of sputum eosinophils
      after allergen compared with placebo treatment. This study shows that anti
      leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids
      are more effective than anti-leukotrienes in attenuating the EARs and improves
      bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled
      glucocorticoids have overall greater efficacy than oral anti-leukotrienes to
      attenuate allergen-induced airway responses in mild asthmatic patients.

PMID- 15575934
TI  - Organization of secondary lymphoid tissue and local IgE formation to
      Staphylococcus aureus enterotoxins in nasal polyp tissue.
AB  - BACKGROUND: Bilateral nasal polyposis (NP) is characterized by high
      concentrations of IgE in NP tissue, which show no relation to the atopic status.
      We aimed to study the relationship between systemic and local IgE formation,
      nasal carriage of Staphylococcus aureus and nasal polyposis. METHODS: In serum
      and nasal tissue homogenates from 24 NP patients and 12 controls, we determined
      concentrations of total IgE and IgE antibodies to inhalant allergens and S.
      aureus enterotoxins (SAEs; A,B,C,D,E,TSST) by ImmunoCAP. Tissue cryosections were
      stained for CD3, CD20, CD38, CD23, FcepsilonRI, IgE and SEA/SEB. RESULTS: We
      demonstrated a higher incidence of S. aureus colonization (17/24) and IgE
      antibodies to SAEs in NP tissue (12/24) compared with controls (3/12 and 0/12,
      respectively). Total IgE and IgE antibodies in serum and NP tissue were
      dissociated because of local polyclonal IgE formation in NP tissue. Staining of
      NP tissue revealed follicular structures characterized by B and T cells, and
      lymphoid accumulations with diffuse plasma cell infiltration. CONCLUSIONS: We
      demonstrated the organization of secondary lymphoid tissue in polyp tissue and a
      polyclonal hyper-immunoglobulinemia E associated with the presence of IgE
      antibodies to SAEs, colonization with S. aureus, and tissue eosinophilia in a
      relevant subgroup of polyp patients.

PMID- 15575935
TI  - Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine.
AB  - Nasal polyp tissue which contains mast cells and eosinophils is similar to the
      inflamed airway mucosa in cellular composition and mediator content. This
      investigation assessed the effect of desloratadine (DL), on activation of cells
      in nasal polyp tissue. Polyps were obtained from 22 patients with chronic
      rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA
      tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and
      incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil
      cationic protein (ECP) and tryptase concentrations in supernatants were measured
      by immunoassays. Desloratadine (1, 10 and 50 microM) inhibited calcium ionophore
      induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE
      induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium
      ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 microM
      of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47%
      and 66% for 1, 10 and 50 microM of DL. Desloratadine 10 microM and 50 microM
      inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA
      sensitive patients when compared with ASA-tolerant patients released at baseline
      significantly more ECP (medians 120.0 microg/ml, range: 69.0-182.0 vs 63.4
      microg/ml, range: 3.7-172.0; P <0.05), but similar amounts of tryptase and LTC4.
      This study demonstrated that DL inhibits activation of both eosinophils and mast
      cells derived from a site of airway mucosal inflammation.

PMID- 15575936
TI  - Increased levels of urinary leukotriene E4 in children with severe atopic
      eczema/dermatitis syndrome.
AB  - BACKGROUND: Leukotrienes are thought to play a role in the pathogenesis of atopic
      eczema/dermatitis syndrome (AEDS). Urinary leukotriene E4 (U-LTE4) is a marker of
      whole-body cysteinyl-leukotriene production. AIMS OF THE STUDY: To evaluate the
      role of leukotrienes in children with AEDS by measuring levels of U-LTE4, and to
      evaluate whether levels of U-LTE4 may reflect disease activity and allergic
      sensitization in AEDS. METHODS: U-LTE4 was measured by enzyme-linked
      immunosorbent assay in 87 children with mild (n=32), moderate (n=34) and severe
      (n=21) AEDS, as well as in 72 nonatopic healthy controls. Fifty-eight of the
      children with AEDS were sensitized to common allergens, and 29 were not. RESULTS:
      Levels of U-LTE4 were higher in children with severe AEDS (140; 66-166
      microg/mmol creatinine, median; quartiles) than in controls (52; 30-90, P <0.05),
      whereas levels of U-LTE4 in moderate and mild disease were similar to controls. U
      LTE4 levels were similar in children with or without sensitization to common
      allergens, but severe AEDS children with sensitization had higher levels of U
      LTE4 than those without sensitization. CONCLUSION: The results suggest a role for
      leukotrienes in the pathogenesis of severe AEDS, and may support a role for
      leukotriene-antagonists in the treatment of this disorder. Levels of U-LTE4 may
      reflect the disease severity and sensitization to allergens in AEDS.

PMID- 15575937
TI  - Mast cells and vasculature in atopic dermatitis--potential stimulus of
      neoangiogenesis.
AB  - BACKGROUND: Atopic dermatitis skin lesions are characterized by inflammatory
      changes and epithelial hyperplasia requiring angiogenesis. As mast cells may
      participate in this process via bidirectional secretion of tissue-damaging
      enzymes and pro-angiogenic factors, the present study aimed to assess the
      occurrence and possible function of mast cells in the papillary dermis and in
      epidermal layers of atopic dermatitis lesions. METHODS: Semi-thin and serial
      sections in combination with immunohistochemistry, histochemistry and
      proliferating cell nuclear antigen (PCNA)-activity assays were used and related
      to epidermal thickness and targeted gene expression studies. RESULTS: Mast cells
      were located in the papillary dermis and migrated through the basal lamina into
      the epidermis of atopic dermatitis lesions. An increased PCNA-activity in cells
      of superficial epidermal layers indicated an activation of keratinocytes and
      stimulation of endothelial growth. Only approximately 30% of the papillary mast
      cells stained with the tryptase were toluidin-blue-positive, and approximately
      80% were chymase positive. A high number of mast cells expressed c-kit. Most
      papillary and epidermal mast cells were localized close to endothelial cells.
      Vascular expression of endoglin (CD105) demonstrated neoangiogenic processes.
      Mast cells stimulation led to the expression of proangiogenic factors. Also, gene
      expression of tissue-damaging factors such as matrix metalloproteinases was
      increased. CONCLUSIONS: These data suggest that in atopic dermatitis, mast cells
      are abundantly localized close to and within the epidermis where they may
      stimulate neoangiogenesis. Via the new vessels, inflammatory cells, together with
      complement components and antibodies, can be transported to the epidermis to aid
      in the defense against environmental antigens and to maintain chronic
      inflammation.

PMID- 15575938
TI  - Association of hepatitis A virus infection with allergic sensitization in a
      population with high prevalence of hepatitis A virus exposure.
AB  - BACKGROUND: An inverse association between allergic sensitization and markers of
      exposure to food-borne and orofecal infections (particularly hepatitis A virus,
      HAV) has been reported. The prevalence of HAV exposure and allergic sensitization
      vary widely in different areas, and vary along with age within a given area. AIM:
      To investigate the association between HAV exposure and allergic sensitization in
      adults from a mostly rural area of Spain. METHODS: An age-stratified random
      sample of 720 subjects was drawn from the population older than 18 years of A
      Estrada, Spain. From 697 eligible subjects, 469 (67.2%, median age 54 years,
      range: 18-92) participated in the study. Positive skin prick tests to a panel of
      aeroallergens defined allergic sensitization. Positive serum HAV antibodies
      (assayed in 465 subjects) defined HAV exposure. RESULTS: The prevalence of HAV
      exposure was 83.6% (95% CI: 80.7-86.5). The prevalence of allergic sensitization
      was lower in subjects with HAV exposure than in patients without it (25.0%vs
      40.0%, OR 0.44, 95% CI: 0.25-0.77, P=0.004), but this association became
      substantially altered after adjusting for age, which was closely linked to both
      allergic sensitization and HAV exposure (adjusted OR 1.15, 95% CI: 0.60-2.19,
      P=0.66). CONCLUSIONS: In a population with high prevalence of HAV exposure, no
      significant association between HAV exposure and allergic sensitization is
      observed after controlling for the confounding effect of age.

PMID- 15575939
TI  - Diagnostic pitfalls in food allergy in children.
AB  - Currently, the diagnostic work-up of suspected food allergy includes skin prick
      tests, the measurement of food specific immunoglobulin E (IgE), and the atopy
      patch test, and double-blind, placebo-controlled food challenges. However, all of
      these methods, even double-blind, placebo-controlled food challenges (DBPCFC),
      may sometimes be misleading. This overview describes several pitfalls for
      standard diagnostic methods such as problems with irritative skin reactions
      mimicking IgE-mediated symptoms, the problem of non-IgE-mediated reactions,
      pitfalls arising from the way foods are prepared or processed, effects of the
      route of exposure, the role of augmentation factors lowering the threshold value
      for clinical reactions, the noncomparability of specific IgE decision points, the
      influence of the timing of diagnostic measures. In addition, the problem of
      alternative diagnostic measures is discussed. In conclusion, there are several
      pitfalls in the diagnostic work-up of food allergy, which may be misleading for
      the physician. Properly performed controlled oral food challenges still represent
      the gold standard for implementing specific diets in food allergic individuals in
      order to avoid both unjustified diets, which may lead to severe impairments in
      growth and development, and to avoid unnecessary symptoms if an underlying food
      allergy is not correctly identified as a cause for the symptoms of the patient.

PMID- 15575940
TI  - Quantification of Blo t 5 in mite and dust extracts by two-site ELISA.
AB  - BACKGROUND: Blomia tropicalis is an important mite species in the tropical and
      sub-tropical regions of the world. Blo t 5 is the major allergen with up to 70%
      sensitization rates in B. tropicalis allergic populations. METHODS: Mice were
      immunized intramuscularly with naked plasmid DNA encoding Blo t 5 gene with in
      vivo electroporation. Blo t 5 monoclonal antibodies were generated using
      methylcellulose-based hybridoma kit. Monoclonal antibody (mAb) 4A7 was
      characterized by two-dimensional electrophoresis immunoblotting. A specific
      quantitative two-site enzyme-linked immunosorbent assay (ELISA) was developed
      with mAb 4A7 and guinea pigs Blo t 5 polyclonal antibody as capture and detection
      antibodies, respectively. This system was tested with Blo t 5 in crude extracts
      and dust samples. RESULTS: A high-affinity mAb 4A7 recognizing several isoforms
      of Blo t 5 has been generated. Monoclonal antibody 4A7 is useful for
      immunoblotting and two-site ELISA. The two-site ELISA developed has a high
      sensitivity, with a detection limit of 10 pg/ml. The assay is species-specific
      and recognized the same epitopes on both native and recombinant Blo t 5. The
      assay developed is able to detect Blo t 5 in commercial diagnostic and
      therapeutic B. tropicalis extract. Blo t 5 quantification in dust samples showed
      that Blo t 5 is present in a high quantity in Singapore dust. CONCLUSIONS: A
      highly sensitive and specific two-site ELISA has been developed. The assay system
      developed is useful for the quantification of Blo t 5 in mite and environmental
      dust extracts.

PMID- 15575941
TI  - Scoring atopic dermatitis in infants and young children: distinctive features of
      the SCORAD index.
AB  - BACKGROUND: Atopic dermatitis (AD) affects infants, children, and adults with a
      wide degree of severity; several scoring systems have been used in trials and
      clinical practice. Infants and young children have a typical distribution of the
      lesions, but a correlation among skin surface involvement, intensity and
      subjective symptoms has not been reported in age groups. AIMS OF THE STUDY: To
      evaluate the clinical features of AD in infants and young children, by using the
      SCORAD index. A simplified scoring method for clinical practice is also
      discussed. METHODS: The SCORAD index was assessed in 63 infants and young
      children with AD [mean age (+/-SD) 17.5 +/- 11.15 months]; the single parameters
      of the index were evaluated, and compared with each other. Serum eosinophil
      cationic protein (s-ECP) and urinary eosinophil protein X (u-EPX) levels were
      determined and correlated with the SCORAD index. RESULTS: The presence of
      erythema, edema/papulation, and oozing/crust was significantly high in these
      patients. A strong positive correlation resulted among the three SCORAD index
      parameters (extent-intensity: P <0.001; extent-subjective symptoms: P <0.001;
      intensity-subjective symptoms: P <0.001). S-ECP and u-EPX levels positively
      correlated to almost every single parameter of the SCORAD index as well as to its
      total. CONCLUSIONS: Distinctive intensity items were found in infants and young
      children with AD. A strong correlation resulted among the extent, intensity, and
      subjective symptoms; each of the three parameters was positively correlated with
      the total SCORAD. Immunologic parameters positively correlated to each of the
      SCORAD index items, which remains the gold standard for assessing disease
      severity in clinical trials.

PMID- 15575942
TI  - Desloratadine prevents compound 48/80-induced mast cell degranulation:
      visualization using a vital fluorescent dye technique.
AB  - BACKGROUND: Desloratadine is a selective H1-antihistamine used in the treatment
      of allergic rhinitis and chronic idiopathic urticaria. Desloratadine inhibits the
      release of allergic inflammatory mediators in vitro. We studied the impact of
      desloratadine on mast cell degranulation due to activation and re-activation by
      the secretagogue, compound 48/80. METHODS: Rat peritoneal eluate containing 5-6%
      mast cells were activated by a low concentration of compound 48/80 in a medium
      containing the vital fluorescent dye, Sulforhodamine-B (SFRM-B, 200 microg/ml),
      which is engulfed by activated mast cells. The fluorescent image of activated
      mast cells was captured digitally and the total fluorescent area was analyzed
      when desloratadine was applied before or after compound 48/80. RESULTS: Mast
      cells were not activated by desloratadine (10(-4) M), SFRM-B (200 microg/ml), or
      diluent alone. A low concentration of compound 48/80 (0.125 microg/ml) induced
      fluorescence, while mast cells lost fluorescent images due to further
      degranulation on re-exposure to compound 48/80. Desloratadine (10(-8)-10(-4) M),
      inhibited compound 48/80-induced mast cell degranulation in a concentration
      dependent manner. Desloratadine also reduced the loss of fluorescent images due
      to re-exposure to compound 48/80. CONCLUSIONS: Desloratadine may have a mast cell
      stabilizing effect at low concentrations in response to repeated mast cell
      activation in vitro.

PMID- 15575943
TI  - Leukotriene CysLT1-receptor antagonism and nasal lysine-aspirin provocation in
      aspirin-induced asthma.

PMID- 15575944
TI  - Beef allergy in adults and children.

PMID- 15575945
TI  - Answer to the letter of Brockow et al. concerning our article 'safety of rush
      insect venom immunotherapy. Results of a retrospective study in 178 patients'.

PMID- 15575946
TI  - Anaphylaxis to quail egg.

PMID- 15575947
TI  - Sheep and goat's milk allergy--a case study.

PMID- 15575948
TI  - Allergic reactions to macadamia nut.

PMID- 15575949
TI  - Correlation between former and new assays of latex IgE-specific determination
      using the K82 and K82 recombinant allergens from the Pharmacia Diagnostics
      laboratory.

PMID- 15575950
TI  - Occupational rhinitis to leek (Allium porrum).

PMID- 15575951
TI  - Safety of sublingual immunotherapy with a monomeric allergoid in very young
      children.

PMID- 15575952
TI  - Over expression of the selectable marker blasticidin S deaminase gene is toxic to
      human keratinocytes and murine BALB/MK cells.
AB  - BACKGROUND: The blasticidin S resistance gene (bsr) is a selectable marker used
      for gene transfer experiments. The bsr gene encodes for blasticidin S (BS)
      deaminase, which has a specific activity upon BS. Therefore, its expression is
      supposed to be harmless in cells. The work reported on herein consisted of
      experiments to verify a possible toxicity of bsr on mammalian cells, which
      include several cell lines and primary cultures. RESULTS: Murine keratinocyte
      BALB/MK and human primary keratinocyte cells transduced with the retroviral
      vector LBmSN, which has an improved expression system of bsr, namely bsrm, died
      in five days after the transduction. Meanwhile the control vector LBSN, which
      expresses bsr, did not provoke cell death. The lethal activity of bsrm was
      observed only in human keratinocytes and BALB/MK cells among the cell types
      tested here. Death appears to be mediated by a factor, which is secreted by the
      BALB/MK transduced cells. CONCLUSION: By our study we demonstrated that the
      expression of bsrm gene is toxic to human keratinocytes and BALB/MK cells. It is
      likely over expression of BS deaminase gene is responsible for the death.

PMID- 15575953
TI  - Educational and economic determinants of food intake in Portuguese adults: a
      cross-sectional survey.
AB  - BACKGROUND: Understanding the influences of educational and economic variables on
      food consumption may be useful to explain food behaviour and nutrition
      policymaking. The aim of this study was to evaluate the importance of educational
      and economic factors in determining food pattern in Portuguese adults. METHODS: A
      cross-sectional study in a representative sample of Portuguese adults (20977
      women and 18663 men). Participants were distributed in four categories according
      to years of education (<or=4, 5-9, 10-12, and >12) and income (<or=314 euros, 315
      547 euros, 548-815 euros, and >815 euros). Logistic regression models were fitted
      to estimate the magnitude of the association between food groups and
      education/income, adjusting for confounders. RESULTS: In both genders, the odds
      favouring milk, vegetable soup, vegetables, fruit, and fish consumption,
      increased significantly with education, for those having >12 years of education
      compared to those with <or=4 years; the odds favouring wine, and spirits
      consumption decreased significantly with education, for those having >12 years of
      education compared to those with <or=4 years. In males, the odds favouring
      starchy foods and meat consumption decreased significantly with income, while for
      milk, the odds increased with higher income (those having >815 euros compared to
      those with <or=314 euros). CONCLUSIONS: The low and high income groups are or
      tend to be similar in regard to several food groups consumption, and access to
      education/information appears to be the key element to a better food pattern as
      indicated by higher frequency of milk, vegetable soup, vegetables, fruit, and
      fish consumption.

PMID- 15575954
TI  - Walkability and self-rated health in primary care patients.
AB  - BACKGROUND: The objective of this study was to investigate the relationship
      between perceived walkability and overall self-rated health among patients who
      use community-based clinics. METHODS: A cross-sectional survey was distributed to
      a convenience sample in three community clinics. Forms were completed by 793
      clinic patients. Multiple logistic regression analysis was to control for the
      effects of demographic variables and lifestyles. RESULTS: Perceiving the
      availability of places to walk was related to better self-rated health. The most
      important places were work (OR = 3.2), community center (OR = 3.12), park (OR =
      2.45) and day care (OR = 2.05). Respondents who said they had zero (OR = .27) or
      one (OR = .49) place to walk were significantly less healthy than persons who
      said they had five or more places to walk. CONCLUSION: Persons who perceived that
      they had no place to walk were significantly less healthy than persons who
      thought they had at least one place to walk (OR = .39). Support for walkable
      neighborhoods and education of patients about options for walking may be in the
      best interests of community medicine patients.

PMID- 15575955
TI  - Characterisation of cytotoxicity and DNA damage induced by the topoisomerase II
      directed bisdioxopiperazine anti-cancer agent ICRF-187 (dexrazoxane) in yeast and
      mammalian cells.
AB  - BACKGROUND: Bisdioxopiperazine anti-cancer agents are inhibitors of eukaryotic
      DNA topoisomerase II, sequestering this protein as a non-covalent protein clamp
      on DNA. It has been suggested that such complexes on DNA represents a novel form
      of DNA damage to cells. In this report, we characterise the cytotoxicity and DNA
      damage induced by the bisdioxopiperazine ICRF-187 by a combination of genetic and
      molecular approaches. In addition, the well-established topoisomerase II poison m
      AMSA is used for comparison. RESULTS: By utilizing a panel of Saccharomyces
      cerevisiae single-gene deletion strains, homologous recombination was identified
      as the most important DNA repair pathway determining the sensitivity towards ICRF
      187. However, sensitivity towards m-AMSA depended much more on this pathway. In
      contrast, disrupting the post replication repair pathway only affected
      sensitivity towards m-AMSA. Homologous recombination (HR) defective irs1SF
      chinese hamster ovary (CHO) cells showed increased sensitivity towards ICRF-187,
      while their sensitivity towards m-AMSA was increased even more. Furthermore,
      complementation of the XRCC3 deficiency in irs1SF cells fully abrogated
      hypersensitivity towards both drugs. DNA-PKcs deficient V3-3 CHO cells having
      reduced levels of non-homologous end joining (NHEJ) showed slightly increased
      sensitivity to both drugs. While exposure of human small cell lung cancer (SCLC)
      OC-NYH cells to m-AMSA strongly induced gammaH2AX, exposure to ICRF-187 resulted
      in much less induction, showing that ICRF-187 generates fewer DNA double strand
      breaks than m-AMSA. Accordingly, when yeast cells were exposed to equitoxic
      concentrations of ICRF-187 and m-AMSA, the expression of DNA damage-inducible
      genes showed higher levels of induction after exposure to m-AMSA as compared to
      ICRF-187. Most importantly, ICRF-187 stimulated homologous recombination in SPD8
      hamster lung fibroblast cells to lower levels than m-AMSA at all cytotoxicity
      levels tested, showing that the mechanism of action of bisdioxopiperazines
      differs from that of classical topoisomerase II poisons in mammalian cells.
      CONCLUSION: Our results point to important differences in the mechanism of
      cytotoxicity induced by bisdioxopiperazines and topoisomerase II poisons, and
      suggest that bisdioxopiperazines kill cells by a combination of DNA break-related
      and DNA break-unrelated mechanisms.

PMID- 15575957
TI  - Bilateral Ramsay Hunt syndrome in a diabetic patient.
AB  - BACKGROUND: Herpes zoster oticus accounts for about 10% cases of facial palsy,
      which is usually unilateral and complete and full recovery occurs in only about
      20% of untreated patients. Bilateral herpes zoster oticus can sometime occur in
      immunocompromised patients, though incidence is very rare. CASE PRESENTATION:
      Diabetic male, 57 year old presented to us with bilateral facial palsy due to
      herpes zoster oticus. Patient was having bilateral mild to moderate sensorineural
      hearing loss. Patient was treated with appropriate metabolic control, anti
      inflammatory drugs and intravenous acyclovir. Due to uncontrolled diabetes,
      glucocorticoids were not used in this patient. Significant improvement in hearing
      status and facial nerve functions were seen in this patient. CONCLUSIONS: Herpes
      zoster causes severe infections in diabetic patients and can be a cause of
      bilateral facial palsy and bilateral Ramsay Hunt syndrome. Herpes zoster in
      diabetic patients should be treated with appropriate metabolic control, NSAIDS
      and intravenous acyclovir, which we feel should be started at the earliest.
      Glucocorticoids should be avoided in diabetic patients.

PMID- 15575956
TI  - Value of supplemental interventions to enhance the effectiveness of physical
      exercise during respiratory rehabilitation in COPD patients. A systematic review.
AB  - BACKGROUND: There is a controversy about the additional benefit of various
      supplemental interventions used in clinical practice to further enhance the
      effectiveness of respiratory rehabilitation in patients with Chronic obstructive
      pulmonary disease (COPD). The aim of this research was to assess randomised
      controlled trials (RCTs) testing the additional benefit of supplemental
      interventions during respiratory rehabilitation in COPD patients. METHODS:
      Systematic review with literature searches in six electronic databases, extensive
      hand-searching and contacting of authors. Two reviewers selected independently
      eligible RCTs, rated the methodological quality and extracted the data, which
      were analyzed considering the minimal important difference of patient-important
      outcomes where possible. FINDINGS: We identified 20 RCTs whereof 18 provided
      sufficient data for analysis. The methodological quality was low and sample sizes
      were too small for most trials to produce meaningful results (median total sample
      size = 28). Data from five trials showed that supplemental oxygen during exercise
      did not have clinically meaningful effects on health-related quality of life
      while improvements of exercise capacity may be even larger for patients
      exercising on room air. RCTs of adding assisted ventilation, nutritional
      supplements or a number of anabolically acting drugs do not provide sufficient
      evidence for or against the use any of these supplemental interventions.
      INTERPRETATION: There is insufficient evidence for most supplemental
      interventions during respiratory rehabilitation to estimate their additional
      value, partly due to methodological shortcomings of included RCTs. Current data
      do not suggest benefit from supplemental oxygen during exercise, although the
      methodological quality of included trials limits conclusions. To appropriately
      assess any of the various supplemental interventions used in clinical practice,
      pragmatic trials on respiratory rehabilitation of COPD patients need to consider
      methodological aspects as well as appropriate sample sizes.

PMID- 15575959
TI  - Open Access to essential health care information.
AB  - Open Access publishing is a valuable resource for the synthesis and distribution
      of essential health care information. This article discusses the potential
      benefits of Open Access, specifically in terms of Low and Middle Income (LAMI)
      countries in which there is currently a lack of informed health care providers -
      mainly a consequence of poor availability to information. We propose that without
      copyright restrictions, Open Access facilitates distribution of the most relevant
      research and health care information. Furthermore, we suggest that the technology
      and infrastructure that has been put in place for Open Access could be used to
      publish download-able manuals, guides or basic handbooks created by healthcare
      providers in LAMI countries.

PMID- 15575958
TI  - HTLV-1 and -2 envelope SU subdomains and critical determinants in receptor
      binding.
AB  - BACKGROUND: Human T-cell leukemia virus (HTLV) -1 and -2 are deltaretroviruses
      that infect a wide range of cells. Glut1, the major vertebrate glucose
      transporter, has been shown to be the HTLV Env receptor. While it is well
      established that the extracellular surface component (SU) of the HTLV envelope
      glycoprotein (Env) harbors all of the determinants of interaction with the
      receptor, identification of SU subdomains that are necessary and sufficient for
      interaction with the receptor, as well as critical amino acids therein, remain to
      be precisely defined. Although highly divergent in the rest of their genomes,
      HTLV and murine leukemia virus (MLV) Env appear to be related and based on
      homologous motifs between the HTLV and MLV SU, we derived chimeric HTLV/MLV Env
      and soluble HTLV-1 and -2 truncated amino terminal SU subdomains. RESULTS: Using
      these SU constructs, we found that the 183 and 178 amino terminal residues of the
      HTLV-1 and -2 Env, respectively, were sufficient to efficiently bind target cells
      of different species. Binding resulted from bona fide interaction with the HTLV
      receptor as isolated SU subdomains specifically interfered with HTLV Env-mediated
      binding, cell fusion, and cell-free as well as cell-to-cell infection. Therefore,
      the HTLV receptor-binding domain (RBD) lies in the amino terminus of the SU,
      immediately upstream of a central immunodominant proline rich region (Env
      residues 180 to 205), that we show to be dispensible for receptor-binding and
      interference. Moreover, we identified a highly conserved tyrosine residue at
      position 114 of HTLV-1 Env, Tyr114, as critical for receptor-binding and
      subsequent interference to cell-to-cell fusion and infection. Finally, we
      observed that residues in the vicinity of Tyr114 have lesser impact on receptor
      binding and had various efficiency in interference to post-binding events.
      CONCLUSIONS: The first 160 residues of the HTLV-1 and -2 mature cleaved SU fold
      as autonomous domains that contain all the determinants required for binding the
      HTLV receptor.

PMID- 15575960
TI  - Factors associated with herbal use among urban multiethnic primary care patients:
      a cross-sectional survey.
AB  - BACKGROUND: The use of herbal supplements in the United States has become
      increasingly popular. The prevalence of herbal use among primary care patients
      varies in previous studies; the pattern of herbal use among urban
      racially/ethnically diverse primary care patients has not been widely studied.
      The primary objectives of this study were to describe the use of herbs by
      ethnically diverse primary care patients in a large metropolitan area and to
      examine factors associated with such use. The secondary objective was to
      investigate perceptions about and patterns of herbal use. METHODS: Data for a
      cross-sectional survey were collected at primary care practices affiliated with
      the Southern Primary-care Urban Research Network (SPUR-Net) in Houston, Texas,
      from September 2002 to March 2003. To participate in the study, patients had to
      be at least 18 years of age and visiting one of the SPUR-Net clinics for routine,
      nonacute care. Survey questions were available in both English and Spanish.
      RESULTS: A total of 322 patients who had complete information on race/ethnicity
      were included in the analysis. Overall, 36% of the surveyed patients (n = 322)
      indicated use of herbs, with wide variability among ethnic groups: 50% of
      Hispanics, 50% of Asians, 41% of Whites, and 22% of African-Americans.
      Significant factors associated with an individual's herbal use were ethnicity
      other than African-American, having an immigrant family history, and reporting
      herbal use by other family members. About 40% of survey respondents believed that
      taking prescription medications and herbal medicines together was more effective
      than taking either alone. One-third of herbal users reported using herbs on a
      daily basis. More Whites (67%) disclosed their herbal use to their health-care
      providers than did African-Americans (45%), Hispanics (31%), or Asians (31%).
      CONCLUSIONS: Racial/ethnic differences in herbal use were apparent among this
      sample of urban multiethnic adult primary care patients. Associated factors of
      herbal use were non-African-American ethnicity, immigrant family history, and
      herbal use among family members. Whereas Hispanics and Asians reported the
      highest rates of herbal use, they were the least likely to disclose their use to
      health-care professionals. These findings are important for ensuring medication
      safety in primary care practices.

PMID- 15575961
TI  - Can mutations in ELA2, neutrophil elastase expression or differential cell
      toxicity explain sulphasalazine-induced agranulocytosis?
AB  - BACKGROUND: Drug-induced agranulocytosis, a severe side effect marked by a
      deficit or absolute lack of granulocytic white blood cells, is a rare side-effect
      of the anti-inflammatory drug sulphasalazine. Mutations in the human neutrophil
      elastase gene (ELA2), causing increased intracellular concentration of this
      serine protease, inhibits neutrophil differentiation in severe congenital
      neutropenia (SCN). Since the clinical symptoms of agranulocytosis and SCN are
      similar, we hypothesized that it may origin from a common genetic variation in
      ELA2 or that sulphasalazine may affect human neutrophil elastase activity and
      protein expression. METHODS: We screened for genetic differences in ELA2 in DNA
      from 36 patients who had suffered from sulphasalazine-induced agranulocytosis,
      and compared them with 72 patients treated with sulphasalazine without blood
      reactions. We also performed in vitro studies of the blood cell lines HL60 and
      U937 after sulphasalazine exposure with respect to cell survival index,
      neutrophil elastase protein expression and activity. RESULTS: None of the
      mutations in ELA2, which previously have been reported to be associated with SCN,
      was found in this material. Protein expression of human neutrophil elastase in
      lymphoma U937 cells was not affected by treatment with concentrations equivalent
      to therapeutic doses. Cell survival of lymphoma U937 and promyelocytic leukemia
      HL-60 cells was not affected in this concentration range, but exhibited a
      decreased proliferative capacity with higher sulphasalazine concentrations.
      Interestingly the promyelocytic cells were more sensitive to sulphasalazine than
      the lymphoma cell line. CONCLUSION: Neutrophil elastase expression and ELA2
      mutations do, however, not seem to be involved in the etilogy of sulphasalazine
      induced agranulocytosis. Why sulphasalazine is more toxic to promyelocytes than
      to lymphocytes remains to be explained.

PMID- 15575962
TI  - Penile metastasis from primary transitional cell carcinoma of the renal pelvis:
      first manifestation of systemic spread.
AB  - BACKGROUND: Almost one-third of all penile metastases are detected at the same
      time as a primary tumor, whereas the remaining two-thirds are detected a mean of
      18 months after the discovery of the primary tumor. Cutaneous metastasis of
      transitional cell carcinoma (TCC) is extremely rare and generally accepted as the
      late manifestation of a systemic spread. CASE PRESENTATION: We report the first
      case of simultaneous penile and lung metastases from a primary TCC of the renal
      pelvis in a 76-year-old man, that occurred 8 years after a left
      nephroureterectomy. CONCLUSIONS: This case report underscores the importance of
      physical examinations of the skin of patients who undergo surgical procedures for
      TCC from bladder as well as from the upper urinary tract, including those
      seemingly without metastatic disease, because of the possibility of skin and
      penile metastatic spread.

PMID- 15575964
TI  - Expression of the Tpl2/Cot oncogene in human T-cell neoplasias.
AB  - BACKGROUND: Tpl2/Cot oncogene has been identified in murine T-cell lymphomas as a
      target of MoMuLV insertion. Animal and tissue culture studies have shown that
      Tpl2/Cot is involved in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF
      alpha) production by T-cells contributing to T-cell proliferation. In the present
      report we examined a series of 12 adult patients with various T-cell
      malignancies, all with predominant leukemic expression in the periphery, for the
      expression of Tpl2/Cot oncogene in order to determine a possible involvement of
      Tpl2/Cot in the pathogenesis of these neoplasms. RESULTS: Our results showed that
      Tpl2/Cot was overexpressed in all four patients with Large Granular Lymphocyte
      proliferative disorders (LGL-PDs) but in none of the remaining eight patients
      with other T-cell neoplasias. Interestingly, three of the LGL-PD patients
      displayed neutropenia, one in association with sarcoidosis. Serum TNF-alpha
      levels were increased in all Tpl2/Cot overexpressing patients while serum IL-2
      was undetectable in all subjects studied. Genomic DNA analysis revealed no DNA
      amplification at the Tpl2/Cot locus in any of the samples analyzed. CONCLUSIONS:
      We conclude that Tpl2/Cot, a gene extensively studied in animal and tissue
      culture T-cell models may be also involved in the development of human LGL-PD and
      may have a role in the pathogenesis of immune manifestations associated with
      these diseases. This is the first report implicating Tpl2/Cot in human T-cell
      neoplasias and provides a novel molecular event in the development of LGL-PDs.

PMID- 15575965
TI  - Age-specific prevalence, transmission and phylogeny of TT virus in the Czech
      Republic.
AB  - BACKGROUND: TT virus is prevalent worldwide, but its prevalence and genotype
      distribution in Central and East-Europe has not been determined. The high
      prevalence of TTV in multiply-transfused patients points to the importance of a
      parenteral mode of transmission, but since more than half of the general
      population is infected other possible routes of transmission must be considered.
      METHODS: In our study, we investigated the epidemiology, transmission and
      phylogeny of TTV in the Czech Republic. The following groups were selected: a
      control group of 196 blood donors, 20 patients with hemophilia, 49 intravenous
      drug users, 100 sex workers, 50 penitentiary prisoners, 208 healthy children aged
      1 to 14 years, 54 cord blood samples, 52 patients with non-A-E hepatitis, 74
      patients with hepatitis C, and 51 blood donors with increased ALT levels. Primers
      specific for the non-coding region were used. The genotype distribution was
      studied in 70 TTV-positive samples. RESULTS: The prevalence rate of TTV among the
      Czech population was 52.6%. We have shown that TTV is not transmitted prenatally.
      Children were infected after birth with two peaks: one at the age of two years
      and the other after the beginning of primary school. Adults have shown a further
      increase in the TTV prevalence with age. The highest TTV prevalence was found in
      the group of patients who had received multiple blood transfusions. The TTV
      prevalence rate in subjects at an increased risk of sexual transmission was not
      significantly higher than in the general population. Genotypes G2 and G1 were
      most prevalent among the Czech population, followed by G8 and G3. The subjects
      positive for markers of HBV and/or HCV infection tested significantly more often
      TTV DNA positive, which is suggestive of a common route of transmission of these
      three infections. CONCLUSIONS: This study on TTV prevalence, mode of transmission
      and age-specific prevalence is the most extensive study performed in Central and
      Eastern Europe. It showed insights into the epidemiology of TTV infection, but
      failed to associate TTV infection with clinical manifestations.

PMID- 15575966
TI  - Estimating genomic coexpression networks using first-order conditional
      independence.
AB  - We describe a computationally efficient statistical framework for estimating
      networks of coexpressed genes. This framework exploits first-order conditional
      independence relationships among gene-expression measurements to estimate
      patterns of association. We use this approach to estimate a coexpression network
      from microarray gene-expression measurements from Saccharomyces cerevisiae. We
      demonstrate the biological utility of this approach by showing that a large
      number of metabolic pathways are coherently represented in the estimated network.
      We describe a complementary unsupervised graph search algorithm for discovering
      locally distinct subgraphs of a large weighted graph. We apply this algorithm to
      our coexpression network model and show that subgraphs found using this approach
      correspond to particular biological processes or contain representatives of
      distinct gene families.

PMID- 15575967
TI  - GOToolBox: functional analysis of gene datasets based on Gene Ontology.
AB  - We have developed methods and tools based on the Gene Ontology (GO) resource
      allowing the identification of statistically over- or under-represented terms in
      a gene dataset; the clustering of functionally related genes within a set; and
      the retrieval of genes sharing annotations with a query gene. GO annotations can
      also be constrained to a slim hierarchy or a given level of the ontology. The
      source codes are available upon request, and distributed under the GPL license.

PMID- 15575968
TI  - The ASRG database: identification and survey of Arabidopsis thaliana genes
      involved in pre-mRNA splicing.
AB  - A total of 74 small nuclear RNA (snRNA) genes and 395 genes encoding splicing
      related proteins were identified in the Arabidopsis genome by sequence comparison
      and motif searches, including the previously elusive U4atac snRNA gene. Most of
      the genes have not been studied experimentally. Classification of these genes and
      detailed information on gene structure, alternative splicing, gene duplications
      and phylogenetic relationships are made accessible as a comprehensive database of
      Arabidopsis Splicing Related Genes (ASRG) on our website.

PMID- 15575969
TI  - Integrating phenotypic and expression profiles to map arsenic-response networks.
AB  - BACKGROUND: Arsenic is a nonmutagenic carcinogen affecting millions of people.
      The cellular impact of this metalloid in Saccharomyces cerevisiae was determined
      by profiling global gene expression and sensitivity phenotypes. These data were
      then mapped to a metabolic network composed of all known biochemical reactions in
      yeast, as well as the yeast network of 20,985 protein-protein/protein-DNA
      interactions. RESULTS: While the expression data unveiled no significant nodes in
      the metabolic network, the regulatory network revealed several important nodes as
      centers of arsenic-induced activity. The highest-scoring proteins included Fhl1,
      Msn2, Msn4, Yap1, Cad1 (Yap2), Pre1, Hsf1 and Met31. Contrary to the gene
      expression analyses, the phenotypic-profiling data mapped to the metabolic
      network. The two significant metabolic networks unveiled were shikimate, and
      serine, threonine and glutamate biosynthesis. We also carried out transcriptional
      profiling of specific deletion strains, confirming that the transcription factors
      Yap1, Arr1 (Yap8), and Rpn4 strongly mediate the cell's adaptation to arsenic
      induced stress but that Cad1 has negligible impact. CONCLUSIONS: By integrating
      phenotypic and transcriptional profiling and mapping the data onto the metabolic
      and regulatory networks, we have shown that arsenic is likely to channel sulfur
      into glutathione for detoxification, leads to indirect oxidative stress by
      depleting glutathione pools, and alters protein turnover via arsenation of
      sulfhydryl groups on proteins. Furthermore, we show that phenotypically sensitive
      pathways are upstream of differentially expressed ones, indicating that
      transcriptional and phenotypic profiling implicate distinct, but related,
      pathways.

PMID- 15575970
TI  - A Drosophila protein-interaction map centered on cell-cycle regulators.
AB  - BACKGROUND: Maps depicting binary interactions between proteins can be powerful
      starting points for understanding biological systems. A proven technology for
      generating such maps is high-throughput yeast two-hybrid screening. In the most
      extensive screen to date, a Gal4-based two-hybrid system was used recently to
      detect over 20,000 interactions among Drosophila proteins. Although these data
      are a valuable resource for insights into protein networks, they cover only a
      fraction of the expected number of interactions. RESULTS: To complement the Gal4
      based interaction data, we used the same set of Drosophila open reading frames to
      construct arrays for a LexA-based two-hybrid system. We screened the arrays using
      a novel pooled mating approach, initially focusing on proteins related to cell
      cycle regulators. We detected 1,814 reproducible interactions among 488 proteins.
      The map includes a large number of novel interactions with potential biological
      significance. Informative regions of the map could be highlighted by searching
      for paralogous interactions and by clustering proteins on the basis of their
      interaction profiles. Surprisingly, only 28 interactions were found in common
      between the LexA- and Gal4-based screens, even though they had similar rates of
      true positives. CONCLUSIONS: The substantial number of new interactions
      discovered here supports the conclusion that previous interaction mapping studies
      were far from complete and that many more interactions remain to be found. Our
      results indicate that different two-hybrid systems and screening approaches
      applied to the same proteome can generate more comprehensive datasets with more
      cross-validated interactions. The cell-cycle map provides a guide for further
      defining important regulatory networks in Drosophila and other organisms.

PMID- 15575971
TI  - Hidden localization motifs: naturally occurring peroxisomal targeting signals in
      non-peroxisomal proteins.
AB  - BACKGROUND: Can sequence segments coding for subcellular targeting or for
      posttranslational modifications occur in proteins that are not substrates in
      either of these processes? Although considerable effort has been invested in
      achieving low false-positive prediction rates, even accurate sequence-analysis
      tools for the recognition of these motifs generate a small but noticeable number
      of protein hits that lack the appropriate biological context but cannot be
      rationalized as false positives. RESULTS: We show that the carboxyl termini of a
      set of definitely non-peroxisomal proteins with predicted peroxisomal targeting
      signals interact with the peroxisomal matrix protein receptor peroxin 5 (PEX5) in
      a yeast two-hybrid test. Moreover, we show that examples of these proteins -
      chicken lysozyme, human tyrosinase and the yeast mitochondrial ribosomal protein
      L2 (encoded by MRP7) - are imported into peroxisomes in vivo if their original
      sorting signals are disguised. We also show that even prokaryotic proteins can
      contain peroxisomal targeting sequences. CONCLUSIONS: Thus, functional
      localization signals can evolve in unrelated protein sequences as a result of
      neutral mutations, and subcellular targeting is hierarchically organized, with
      signal accessibility playing a decisive role. The occurrence of silent functional
      motifs in unrelated proteins is important for the development of sequence-based
      function prediction tools and the interpretation of their results. Silent
      functional signals have the potential to acquire importance in future
      evolutionary scenarios and in pathological conditions.

PMID- 15575972
TI  - MONKEY: identifying conserved transcription-factor binding sites in multiple
      alignments using a binding site-specific evolutionary model.
AB  - We introduce a method (MONKEY) to identify conserved transcription-factor binding
      sites in multispecies alignments. MONKEY employs probabilistic models of factor
      specificity and binding-site evolution, on which basis we compute the likelihood
      that putative sites are conserved and assign statistical significance to each
      hit. Using genomes from the genus Saccharomyces, we illustrate how the
      significance of real sites increases with evolutionary distance and explore the
      relationship between conservation and function.

PMID- 15575973
TI  - Model-independent fluxome profiling from 2H and 13C experiments for metabolic
      variant discrimination.
AB  - We introduce a conceptually novel method for intracellular fluxome profiling from
      unsupervised statistical analysis of stable isotope labeling. Without a priori
      knowledge on the metabolic system, we identified characteristic flux fingerprints
      in 10 Bacillus subtilis mutants from 132 2H and 13C tracer experiments. Beyond
      variant discrimination, independent component analysis automatically mapped
      several fingerprints to their metabolic determinants. The approach is flexible
      and paves the way to large-scale fluxome profiling of any biological system and
      condition.

PMID- 15575974
TI  - Color blind.

PMID- 15575975
TI  - Silencing of transposons in plant genomes: kick them when they're down.
AB  - Recent progress in understanding the silencing of transposable elements in the
      model plant Arabidopsis has revealed an interplay between DNA methylation,
      histone methylation and small interfering RNAs. DNA and histone methylation are
      not always sufficient to maintain silencing, and RNA-based reinforcement can be
      needed to maintain as well as initiate it.

PMID- 15575976
TI  - Tetraodon genome confirms Takifugu findings: most fish are ancient polyploids.
AB  - An evolutionary hypothesis suggested by studies of the genome of the tiger
      pufferfish Takifugu rubripes has now been confirmed by comparison with the genome
      of a close relative, the spotted green pufferfish Tetraodon nigroviridis. Ray
      finned fish underwent a whole-genome duplication some 350 million years ago that
      might explain their evolutionary success.

PMID- 15575977
TI  - The origin of recent introns: transposons?
AB  - The long-standing question of how genes acquire introns has provoked much debate.
      A recent study makes considerable progress by identifying numerous recently
      gained introns in nematodes - although it remains difficult to distinguish
      definitively between models of intron gain.

PMID- 15575978
TI  - Chromatin architecture and gene expression in Escherichia coli.
AB  - Two recent genome-scale analyses underscore the importance of DNA topology and
      chromatin structure in regulating transcription in Escherichia coli.

PMID- 15575980
TI  - Why genomics is more than genomes.
AB  - A report on the 2004 meeting on Molecular Genetics of Bacteria and
      Bacteriophages, Cold Spring Harbor, USA, 25-29 August 2004.

PMID- 15575979
TI  - The Janus kinases (Jaks).
AB  - The Janus kinase (Jak) family is one of ten recognized families of non-receptor
      tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and
      Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein
      has a kinase domain and a catalytically inactive pseudo-kinase domain, and they
      each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin,
      radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are
      activated and phosphorylate the receptors, creating docking sites for signaling
      molecules, especially members of the signal transducer and activator of
      transcription (Stat) family. Mutations of the Drosophila Jak (Hopscotch) have
      revealed developmental defects, and constitutive activation of Jaks in flies and
      humans is associated with leukemia-like syndromes. Through the generation of Jak
      deficient cell lines and gene-targeted mice, the essential, nonredundant
      functions of Jaks in cytokine signaling have been established. Importantly,
      deficiency of Jak3 is the basis of human autosomal recessive severe combined
      immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been
      developed, forming a new class of immunosuppressive drugs.

PMID- 15575981
TI  - Mice get their annual check-up.
AB  - A report on the 2004 meeting on Mouse Molecular Genetics, Cold Spring Harbor,
      USA, 1-5 September 2004.

PMID- 15575982
TI  - Translational regulation of gene expression.
AB  - A report on the Cold Spring Harbor Laboratory meeting 'Translational Control',
      Cold Spring Harbor, USA, 7-12 September 2004.

PMID- 15575983
TI  - A dot-blot ELISA comparable to immunoblot for the specific diagnosis of human
      parastrongyliasis.
AB  - A dot-blot enzyme-linked immunosorbent assay (dot-blot ELISA) using an
      electroeluted 31-kDa glycoprotein from adult worms of Parastrongylus cantonensis
      as the specific antigen was evaluated for the immunological diagnosis of patients
      infected with P. cantonensis. The sensitivity and specificity for the detection
      of serum antibody to P. cantonensis in dot-blot ELISA were both 100%, as
      determined with serum samples of ten P. cantonensis-infected patients, 60
      patients with other related parasitic infections, and 20 uninfected controls. The
      test was as sensitive and specific as the immunoblot test which revealed a
      reactive band of 31 kDa. Both the dot-blot ELISA and immunoblot detected all sera
      from ten P. cantonensis-infected individuals, but not with those of other
      heterologous parasitoses (gnathostomiasis, toxocariasis, filariasis,
      paragonimiasis, cysticercosis and malaria) or sera from healthy controls. The dot
      blot ELISA is much simpler to perform than the immunoblot technique, and the test
      can be applied under field conditions where sophisticated facilities are lacking.

PMID- 15575984
TI  - Delayed macrofilaricidal activity of diethylcarbamazine against Brugia pahangi in
      Mongolian jirds.
AB  - The macrofilaricidal activity of diethylcarbamazine (DEC) was confirmed in jirds
      infected with Brugia pahangi. Seventy jirds were inoculated subcutaneously with
      100 infective larvae. At 20 weeks post-infection, the microfilaraemic jirds were
      divided into two groups, untreated and treated. For the treated group, 200 mg kg(
      1) of DEC was injected intraperitoneally for 5 consecutive days. One, 4, 8, 12,
      16 and 27 weeks after the final treatment, 4-7 jirds in each group were
      sacrificed to measure adult worm burdens. The number of adult worms recovered
      from treated jirds was comparable to controls at earlier necropsy (1 and 4 weeks
      post-treatment). However, at late necropsy (8 weeks and later) the recovery rate
      of adult worms in treated jirds was significantly lower than that in untreated
      controls, indicating an adultcidal effect of DEC. The present study demonstrates
      that DEC requires 8 weeks to kill B. pahangi adult worms in jirds and that the
      Mongolian jird is a useful model for screening antifilarial activity.

PMID- 15575985
TI  - Intestinal helminth parasites in flounder Platichthys flesus from the River
      Thames: an infracommunity analysis.
AB  - An analysis was undertaken of intestinal helminth communities in flounder
      Platichthys flesus from two sites on the River Thames. A comparison was made
      between helminth community richness and diversity from these sites at the
      component and infracommunity levels. At the component community level, a richer
      and more diverse parasite community was found in flounder from the Tilbury
      location (marine influence) than that from the Lots Road location (freshwater
      influence). At the infracommunity level, more parasite species and parasite
      individuals per host were found at Lots Road and the percentage of similarity
      values were low at both locations. Helminth species with high prevalence values
      in the parasite communities of the flounder are the dominant species in any
      individual fish, harbouring multi-specific infections. The presence of more
      invertebrate species, which are intermediate hosts in the helminth life cycle in
      the Thames, fish vagility and the high prevalence and abundance values of
      Pomphorhynchus laevis in the flounder, may explain the differences between the
      two locations.

PMID- 15575986
TI  - Wet-days: are they better indicators of Ascaris infection levels?
AB  - Seasonal variation in a particular area may influence the occurrence of helminth
      infections and determining such fluctuations may help to maximize the beneficial
      effects of mass treatment. This study determined the seasonal variations in
      infection levels of Ascaris lumbricoides between March 2000 and June 2001 in two
      selected low-country plantations. Four hundred and seventy seven persons aged
      between 2 and 74 years (median 13) participated. Stools were tested using the
      Kato-Katz method and the prevalence and intensity of infection determined. All
      persons were treated with a single dose of mebendazole. Monthly follow-ups were
      undertaken with similar stool examinations and treatment given if found positive.
      Infection and re-infection rates were calculated each month. Rainfall and
      temperature were recorded each day. Total rainfall, number of wet-days and mean
      temperature was calculated for each month. The prevalence of Ascaris infection
      was 53.4% and 51.0% at Maliboda and Ayr estates respectively. Highest infection
      and re-infection rates at Maliboda (37.7%, 37.2%) occurred in June and at Ayr
      (13.3%, 25.9%) in October 2000 respectively. During the study period, the mean
      rainfall was 28.1 cm (range 7.4-63.9 cm) and mean temperature 27.6 degrees C
      (range 22.1 degrees -34.4 degrees C). Significant correlations (P<0.05) were
      found between the re-infection rate and rainfall, temperature and the number of
      wet-days. Similar correlations were observed with the infection rate and
      temperature and the number of wet-days. Ascaris infections were found to
      correlate significantly only with the number of wet-days in a month (P<0.01).
      Thus, the number of wet-days appears to be a better indicator of Ascaris
      infections than total rainfall or mean temperature.

PMID- 15575987
TI  - Induced eosinophilia and proliferation in Angiostrongylus cantonensis-infected
      mouse brain are associated with the induction of JAK/STAT1, IAP/NF-kappaB and
      MEKK1/JNK signals.
AB  - Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus
      cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand,
      and Japan. Although eosinophilia is an important clinical manifestation of A.
      cantonensis infection, the role of eosinophils in the progress of the infection
      remains to be elucidated. In this experiment, we show that A. cantonensis-induced
      eosinophilia and inflammation might lead to the induction of IAP/NF-kappaB,
      JAK/STAT1 and MEKK1/JNK signals. The phosphorylation levels of JAK and JNK,
      STAT1, IAP, NF-kappaB and MEKK1 protein products were significantly increased
      after 12 days or 15 days of A. cantonensis infection. However, no significant
      differences in MAPKs such as Raf, MEK-1, ERK1/2 and p38 expression were found
      between control and infected mice. The activation potency of JAK/STAT1, IAP/NF
      kappaB and MEKK1/JNK started increasing on day 3, with significant induction on
      day 12 or day 15 after A. cantonensis infection. Consistent results were noted in
      the pathological observations, including eosinophilia, leukocyte infiltration,
      granulomatous reactions, and time responses in the brain tissues of infected
      mice. These data suggest that the development of brain injury by eosinophilia of
      A. cantonensis infection is associated with activation of JAK/STAT1 signals by
      cytokines, and/or activation of MEKK1/JNK by oxidant stress, and/or activation of
      NF-kappaB by increasing IAP expression.

PMID- 15575988
TI  - Helminth infracommunities of a population of the Gran Canaria giant lizard
      Gallotia stehlini.
AB  - A survey of gastro-intestinal helminth communities of Gallotia stehlini (Sauria:
      Lacertidae) from Gran Canaria island (Canary Archipelago, Spain), was conducted
      to determine the prevalence, abundance and species diversity of intestinal
      parasites in these lizards. Pharyngodonid nematodes were the most common
      intestinal helminths, three species being Gallotia specialists. Helminth
      infracommunities of G. stehlini were rich and appear to be closer to the
      interactive end of the continuum isolationist-interactive helminth communities,
      according to the high values of helminth diversity. It is the first case of a
      saurian reptile showing this kind of diverse helminth infracommunity, produced by
      a large size, a wide-ranging plant diet and exposure to helminths with direct
      life-cycles.

PMID- 15575989
TI  - Helminths infecting the parthenogenetic whiptail lizard Cnemidophorus nativo in a
      restinga habitat of Bahia State, Brazil.
AB  - A sample of 101 specimens of the unisexual whiptail lizard Cnemidophorus nativo
      (Squamata; Teiidae) from a coastal site in Bahia State, Brazil were examined for
      the presence of endoparasites. Of these, 35 (34.7%) harboured helminths. Six
      helminth species were recovered from C. nativo, including five nematodes
      (Physaloptera retusa, Physalopteroides venancioi, Subulura lacertilia,
      Skrjabinelazia intermedia and Parapharyngodon sp., and one cestode (Oochoristica
      ameivae), all representing new host records. Most lizards were infected by a
      single species of helminth and none by more than three. Infection rates were
      neither significantly influenced by host body size nor by environmental factors.
      The results are compared with data from studies on other whiptail species in both
      South and North America.

PMID- 15575990
TI  - Influence of cadmium exposure on the incidence of first intermediate host
      encystment by Echinoparyphium recurvatum cercariae in Lymnaea peregra.
AB  - The effect of cadmium exposure of the snail first intermediate host Lymnaea
      peregra on the incidence of encystment of Echinoparyphium recurvatum (Digenea:
      Echinostomatidae) cercariae without emergence from the snail was investigated.
      Exposure to 100 microg l(-1) Cd for 72 h caused a significant increase in the
      incidence of first host encystment when compared to controls. In addition,
      autometallographic staining of E. recurvatum daughter rediae and developing
      cercariae showed that there was metal accumulation within their body tissues. The
      significance of these findings to parasite transmission in metal-polluted
      environments is discussed.

PMID- 15575991
TI  - Prevalence of Libyostrongylus douglassii in commercially reared ostriches in the
      highveld region of Zimbabwe.
AB  - A total of 435 freshly dropped faecal samples were collected from 11 randomly
      selected ostrich farms during September and November 2002 to determine the
      prevalence of Libyostrongylus douglassii (ostrich wireworm) in the highveld
      region of Zimbabwe. Samples, which consisted of 339 samples from breeder birds
      and 96 samples from pre-slaughter grower birds were screened for nematode eggs
      using the modified McMaster technique before being individually cultured in an
      incubator at 28 degrees C. Cultures were examined for the presence of L.
      douglassii third stage larvae (L3). Using faecal egg counts, eight of 11 farms
      (72.7%) were positive for L. douglassii in breeders but no eggs were detected in
      the growers. The faecal culture method detected wireworm larvae in the breeding
      stock of all farms that were surveyed (100%) and five of the eight farms (62.5%)
      which had grower birds. Libyostrongylus douglassii was detected in all farms
      (100%) based on the faecal culture method. Libyostrongylus douglassii was
      detected for the first time in 7 of 11 farms (64%) surveyed. Data from
      questionnaires designed to assess farm management practices showed that four out
      of seven (57.1%) of the ostrich producers were unaware of the importance of
      wireworms in ostriches. The farms did not have a regular deworming programme for
      their birds and no faecal samples were sent routinely to the veterinary
      laboratory for screening of wireworms. Wireworm infections were not taken into
      consideration by farmers during buying and selling of birds.

PMID- 15575992
TI  - The prevalence, intensity and clinical signs of urinary schistosomiasis in Imo
      state, Nigeria.
AB  - Urine samples were assayed for urinary schistosomiasis in four local government
      areas (LGA) of Imo State, Nigeria between May 1998 and September 2000. A total of
      3504 persons were sampled, with 880 (25.1%) being positive for urinary
      schistosomiasis, based on records of eggs of Schistosoma haematobium. The
      prevalence of S. haematobium infection differed in the various LGAs, with Oguta
      (38.9%) and Owerri-West (10.4%) showing the highest and the lowest values,
      respectively. Prevalence was higher in males (67.4%) than in females (32.6%) and
      in subjects 11-20 years of age (31.5%), while prevalence varied among different
      occupational groups, with farmers ranking the highest (41.6%). Visible haematuria
      was the predominant symptom (P<0.05). Of 880 persons positive for eggs of S.
      haematobium, 452 (51.4%) had visible haematuria, followed by suprapubic pains 214
      (24.3%) and painful micturition 97 (11.0%). Although 367 (10. 5%) of the sampled
      subjects with eggs of S. haematobium showed no visible haematuria, 513 (14.6%)
      clearly demonstrated haematuria.

PMID- 15575993
TI  - Effects of Schistosoma mansoni infection on inorganic elements in the snail
      Biomphalaria glabrata.
AB  - Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to
      study element ions in whole bodies of uninfected Biomphalaria glabrata snails and
      those experimentally infected with larval Schistosoma mansoni trematodes.
      Infected snails were analysed 8 weeks post-infection. Cohort snails that were
      left uninfected were analysed at the same time as the infected snails. Sixteen
      elements (aluminum, boron, barium, calcium, cadmium, copper, iron, potassium,
      magnesium, manganese, sodium, nickel, lead, selenium, tin and zinc) were found to
      be present in infected and uninfected whole bodies at concentrations above the
      detection limit of the ICP-AES analysis. Of these, calcium, cadmium, manganese
      and sodium were present in significantly higher amounts (Student's t-test,
      P<0.05) in whole infected versus whole uninfected snails. Variations in the
      present results compared with other studies reflect intrinsic differences in the
      larval trematode-snail systems used.

PMID- 15575994
TI  - Adult 175 kDa collagenase antigen of Setaria cervi in immunoprophylaxis against
      Brugia malayi in jirds.
AB  - A 175 kDa antigen fraction with collagenase activity was isolated and purified
      from somatic extracts of adult Setaria cervi females using column chromatography
      involving consecutive steps of DEAE-Sepharose CL6B and Sephadex G-100. The
      optimum pH for 175 kDa collagenase was found to be pH 7.0. Sensitivities to a
      variety of inhibitors and activators indicated that the 175 kDa coIlagenolytic
      enzyme was metalloserine in nature. The enzyme hydrolysed a variety of protein
      substrates such as haemoglobin, casein, azocasein (general substrates) and
      collagen, FALGPA (furanoyl-acryloyl-leu-gly-pro-ala), the specific substrate of
      collagenase. The enzyme showed 57% inhibition by jird anti-somatic collagenase
      antibodies and reacted insignificantly with normal jird sera. Further analysis
      was undertaken on the immunoprophylactic potential of 175 kDa collagenase in
      inducing immunity against Brugia malayi (a human filarial parasite) in jirds
      (Meriones unguiculatus) in vitro and in situ. Immune sera of jirds raised against
      this antigen promoted partial adherence of peritoneal exudate cells to B. malayi
      microfilariae (mf) and infective larvae (L3) in vitro and induced partial
      cytotoxicity to the parasites within 48 h. The anti-S. cervi 175 kDa antigen
      serum was more effective in inducing cytotoxicity to B. malayi L3, than mf. In
      the microchambers implanted inside immune jirds, host cells could migrate and
      adhere to the mf and infective larvae thereby killing them partially within 48 h.

PMID- 15575995
TI  - Helminth parasites of the Eurasian otter Lutra lutra in southwest Europe.
AB  - The helminth fauna in 109 Eurasian otters (Lutra lutra L.) from France, Portugal
      and Spain was analysed, together with 56 faecal samples collected in Portugal and
      23 fresh stools from otters included in a reintroduction programme. Seven
      helminth species were found in L. lutra in southwest Europe: Phagicola sp.
      (Trematoda), Aonchotheca putorii, Eucoleus schvalovoj, Strongyloides lutrae,
      Anisakis (third stage larvae) and Dirofilaria immitis (Nematoda), and
      Gigantorhynchus sp. (Acanthocephala). Eucoleus schvalovoj was the dominant
      species throughout southwest Europe. Strongyloides lutrae was significantly more
      prevalent in the Iberian Peninsula than in France. Apart from these two dominant
      nematodes and A. putorii, the other helminth species were incidental parasites of
      L. lutra in southwest Europe. The helminth fauna of L. lutra in southwest Europe
      is, in general, poorer than that reported in eastern Europe and in all other
      aquatic mustelids in southwest Europe. Phagicola specimens are reported for the
      first time in a non-marine wild carnivore in Europe. The prevalences of E.
      schvalovoj and S. lutrae obtained by necropsy were higher than those observed by
      coprological analysis using a formalin-ether concentration method (Ritchie).
      Nevertheless, the culture of fresh faeces appears to be the best method to study
      infection of L. lutra by Strongyloides.

PMID- 15575996
TI  - Component community dynamics of larval trematodes in the freshwater snail
      Semisulcospira nakasekoae in the Uji River, central Japan.
AB  - The component community of larval trematodes in the freshwater snail
      Semisulcospira nakasekoae (Caenogastropoda: Sorbeoconcha: Pleuroceridae) was
      surveyed over 13 months from April 1996 to April 1997 inclusive. Temporal and
      spatial fluctuation of trematode prevalence, the frequency of multiple
      infections, and the duration of cercarial shedding were examined as factors that
      might affect trematode community structure. The spatial prevalence of some
      species varied significantly, but the dynamics were too small to allow an
      explanation of the overall pattern. The prevalence of sanguinicolids fluctuated
      temporally, despite a stable size distribution in the host populations (> 6.0 mm
      shell width), suggesting the life-cycle phenology of this species. Some pairs of
      species had statistically positive associations, but no pairs had negative
      associations. This shows the importance of positive association possibly as a
      result of suppression of the host defensive response on trematode community
      structures in molluscan hosts. The length of the patent period, which is part of
      the persistent period, varied among trematode species, suggesting it to be one of
      the factors determining prevalence in the host population.

PMID- 15575997
TI  - Effects of copper sulphate on in vitro encystment of the cercariae of Echinostoma
      caproni.
AB  - The effects of various concentrations of copper sulphate were studied on in vitro
      encystment of Echinostoma caproni in a Locke's-artificial spring water (ASW)
      (1:1) medium. Cercariae were killed in 10,000 mg l(-1) CuSO4 in Locke's-ASW (1:1)
      within 24 h and extruded cystogenous material to produce an abnormal cyst wall.
      The 'emergency response' of encystment to high concentrations of copper reported
      for Parorchis acanthus cercariae did not occur in E. caproni. Concentrations of
      1000 mg l(-1) and 100 mg l(-1) CuSO4 in Locke's-ASW (1:1) also killed the
      cercariae without encystment by 48 h. A concentration of 10 mg l(-1) CuSO4 in
      Locke's-ASW (1:1) allowed for normal in vitro encystment within 48 h and these
      cysts were capable of excystation in a trypsin-bile salts medium.

PMID- 15575998
TI  - Metacercariae of Clinostomum attenuatum in Ambystoma tigrinum mavortium, Bufo
      cognatus and Spea multiplicata from west Texas.
AB  - Tissues from barred tiger salamanders (Ambystoma tigrinum mavortium), Great
      Plains toads (Bufo cognatus) and New Mexico spadefoots (Spea multiplicata)
      collected from 16 playa wetlands in Texas during 1999 and 2000 were examined by
      light microscopy. Digenean cysts were primarily distributed subcutaneously
      throughout the specimens and occasionally coelomic invasion was noted. The
      parasites within the cysts were 1.5-2 mm in diameter, with a thin (c. 10 microm
      wide) eosinophilic-staining tegument, two suckers (oral and ventral), posteriorly
      located primordial genitalia and paired digestive caeca. These digeneans were
      identified as the metacercariae of Clinostomum attenuatum. This is the first
      record of Clinostomum attenuatum in these amphibian species.

PMID- 15575999
TI  - Munchausen's syndrome in neurosurgery: report of two cases and review of the
      literature.
AB  - OBJECTIVE AND IMPORTANCE: Munchausen's syndrome is a rare psychiatric condition,
      in which patients seek medical treatment for factitious or self-induced medical
      problems. Reports in the literature of postoperative Munchausen's syndrome are
      extremely rare. The major obstacle to improving management of the patients with
      Munchausen's syndrome is increasing physicians' awareness and recognition of the
      disease. Although Munchausen's syndrome is rare, physicians probably will
      encounter at least one such patient at some point during their career and
      therefore should be aware of this disorder. CLINICAL PRESENTATION: We report two
      documented cases of postoperative Munchausen's syndrome in patients who underwent
      cranial neurosurgery. Both patients received complex flaps for closure of their
      cranial defects. Both patients later admitted to deliberately reopening their
      cranial wounds because of a psychological desire to continue their illness.
      INTERVENTION: The primary therapeutic objective is to achieve wound healing and
      stop the cycle of surgical procedures. Immediate confrontation with the patient
      often does more harm than good. Instead, psychiatric consultation, with the
      potential for nonsurgical management and behavior modification, should be
      obtained. CONCLUSION: Munchausen's syndrome is a rare psychiatric diagnosis,
      especially in the postoperative patient. The common clues to diagnosis are: 1) a
      nonhealing wound in the absence of risk factors for wound failure, 2) a history
      of psychiatric illness, 3) repeated bleeding from the wound site, and 4) a desire
      to continue the sick role. Early detection will allow proper psychiatric referral
      to prevent injuries to the patient, abuses to the medical system, and unnecessary
      operations.

PMID- 15576000
TI  - Evidence-based pharmacotherapy of Generalized Anxiety Disorder.
AB  - Generalized Anxiety Disorder (GAD) is a common and often disabling disorder. This
      paper reviews the pharmacological treatment of GAD, based on the findings of
      published meta-analyses and randomized placebo-controlled studies. In doing so,
      it aims to address three fundamental questions: What is the first-line treatment
      for GAD? How long should treatment continue? What is the best intervention in
      patients who do not respond to first-line and second-line treatments? Due to
      their efficacy in GAD and comorbid anxiety and depressive disorders, their
      tolerability and safety, certain selective serotonin re-uptake inhibitors
      (escitalopram, paroxetine, sertraline) should be considered the first-line
      treatment for most patients, although the serotonin-noradrenaline re-uptake
      inhibitor venlafaxine is a reasonable alternative. Little is known about the
      optimal length of therapy after response to acute treatment but relapse
      prevention studies with paroxetine suggest that continuation treatment should
      last for at least 6 months. The management of patients who do not respond to
      first-line treatment is uncertain, but some patients may benefit from certain
      tricyclic antidepressants, buspirone, or pregabalin.

PMID- 15576001
TI  - Drugs vs OR time.

PMID- 15576002
TI  - The role of bisphosphonates in the management of bone metastases in prostate
      cancer.
AB  - Bone metastases are associated with significant skeletal-related morbidity that
      negatively correlates with quality of life and survival in patients with prostate
      cancer. Once prostate cancer has metastasized to bone, the median survival of
      patients is approximately 30 to 53 months; therefore, the chronic consequences of
      bone complications must be taken into consideration when developing long-term
      therapeutic strategies in this patient population. In addition to the bone
      damaging effects of metastases, bone loss related to long-term hormonal therapy,
      as well as age-related bone loss, further compromise bone integrity in patients
      with advanced prostate cancer. This article reviews the burden of skeletal
      complications in patients with prostate cancer, and the evidence for the use of
      bisphosphonates for the treatment of skeletal morbidity in this patient
      population.

PMID- 15576003
TI  - Percutaneous ultrasonic lithotripsy (PUL) after shock wave lithotripsy (SWL)
      failure.
AB  - OBJECTIVE: Shock wave lithotripsy (SWL) is an attractive initial treatment for
      nephrolithiasis. Unfortunately, a significant number of stones are resistant to
      SWL therapy and require subsequent percutaneous ultrasonic lithotripsy (PUL) for
      definitive treatment. Our objective was to determine if previous SWL had adverse
      effects on PUL success and if there were differences between the patients
      undergoing primary PUL and those undergoing PUL after SWL failure. MATERIALS AND
      METHODS: In 2001, 108 PULs were performed at our institution, of which 40 (37%)
      were performed after SWL failure. Stone location, anesthesia time, stone
      composition and size, and complication rates were compared between patients who
      had PUL alone and those who underwent PUL after SWL failure. Anesthesia time was
      considered a reflection of technical difficulty of the case. RESULTS: Stone
      composition differed between the SWL failure and primary PUL groups. Cystine
      stones were found to be more common in the ESWL failure group and calcium oxalate
      monohydrate stones more common in the primary PUL group. There was not a
      statistically significant difference in stone size, anesthesia time or
      complication rates, between the PUL alone and PUL after SWL failure groups.
      CONCLUSION: PUL remains a reliable and safe treatment of nephrolithiasis. Prior
      SWL does not affect efficacy, technical difficulty, or postoperative
      complications of subsequent PUL. Based on our data, prior SWL should not be
      considered a negative factor in PUL outcomes. Stone composition should be
      considered a prognostic indicator of SWL failure and alert the surgeon that
      primary PUL may be indicated.

PMID- 15576004
TI  - An unusual case of concurrent breast and prostate cancer.
AB  - Breast and prostate cancer occurring concurrently is a rare occurrence. However,
      the recent literature has reported that there is an increased incidence of male
      breast cancer in prostate cancer patients. The authors describe the case of a man
      who presented with breast cancer, which was preceded by prostate cancer. There
      are some common features in terms of the etiology, diagnosis and treatment of
      these two tumors which are discussed.

PMID- 15576005
TI  - Benign paratesticular Schwannoma.
AB  - Scrotal masses are common findings on genitourinary exam. The majority of these
      masses are benign and can be identified via history and physical exam alone.
      Question as to the origin of these masses merits additional evaluation that
      typically consists of an imaging study (e.g., ultrasound) and possibly serum
      tumor markers (e.g., HCG and AFP). In the end, surgical exploration may be
      necessary. Herein, the authors describe a rare case of benign paratesticular
      Schwannoma and discuss the clinical presentation and treatment of scrotal masses.

PMID- 15576006
TI  - Laparoscopic robotic pyeloplasty using the Zeus Telesurgical System.
AB  - We present the initial clinical experience using a robot to perform a
      laparoscopic dismembered pyeloplasty at a Canadian centre. Five patients were
      confirmed to have ureteropelvic junction obstructions through nuclear renography,
      cross sectional imaging and intravenous pyelography. After performing a
      retrograde ureteropyelography and double J stent placement, laparoscopic
      dismembered pyeloplasty was performed by a single surgeon at a remote workstation
      using the ZeusTM Telepresence Surgery System (Intuitive Surgicala). The mean
      total operative time was 225+/-48 minutes, anastomotic time was 71+/-16 minutes,
      and the mean time required to set-up the robot was 30+/-17 minutes. The estimated
      blood loss was less than 100 ml in each case. A mean total of 22+/-10 mg of
      morphine sulfate equivalents were used for analgesia, and the patients were
      discharged home after a mean of 58+/-10 hrs. There were no robotic failures, and
      all evaluable patients are free of pain and demonstrable obstruction. One patient
      developed a delayed urine leak, which resolved with percutaneous drainage. The
      robot provides the ability to perform complicated operations with precision
      through elimination of tremor, scaling of motion, and through the use of
      'wristed' instruments that enhance the freedom of movement normally limited by
      straight-shafted laparoscopic needle drivers. The development of robotic
      telesurgery is still in its infancy, and the significance of its role in urologic
      surgery continues to be evaluated.

PMID- 15576007
TI  - The urological personality: is it unique?
AB  - OBJECTIVES: To develop a preliminary characterization of the urological
      personality. METHODS: Thirty-four urology residents (29 male) from all eleven
      Canadian training programs anonymously completed the Revised NEO personality
      inventory (NEO-PI-R(c)), a commercially available validated personality
      assessment tool in which participants agree or disagree with a compilation of 240
      statements. A score is generated in each of five character traits according to
      the five factor theory of personality: extraversion (E), openness (O),
      conscientiousness (C), agreeableness (A) and neuroticism (N). The group mean on
      each scale was compared to the normative mean for the general adult population
      using one-sample, two-tailed t tests. RESULTS: Urology residents scored
      significantly higher than the general population on three of the five personality
      factors: extraversion (E) (p<.001), openness (O) (p<.02) and conscientiousness
      (C) (p<.05). There was no significant difference from norms in agreeableness (A)
      or neuroticism (N). CONCLUSIONS: The high scores in 'extraversion' reflect the
      social, warm, active and talkative nature of urology residents. As well, urology
      residents tend to be willing to entertain new ideas and are purposeful and
      determined based on their high scores on 'openness' and 'conscientiousness'
      respectively. Canadian urology residents possess a distinct personality in
      comparison to the general population. These provocative findings should be
      interpreted with caution. If confirmed on a wider basis, the data may be helpful
      in career counseling and resident selection. Future studies examining differences
      between the urological personality and other surgical subspecialties may further
      refine applications of the data.

PMID- 15576008
TI  - Bladder leiomyoma: report of two cases and literature review.
AB  - Mesenchymal tumors of the urinary bladder are rare and the majority of them are
      malignant. We report two cases of leiomyoma of the urinary bladder presenting
      with symptoms of bladder outlet obstruction. The first patient was managed with
      staged transurethral resections, and the second with holmium laser transurethral
      inoculation. The outcome was excellent in both cases. A review of the literature
      is also outlined.

PMID- 15576009
TI  - High-performance liquid chromatographic determination of selected flavonols in
      Ginkgo biloba solid oral dosage forms.
AB  - PURPOSE: This paper describes a validated high-performance liquid chromatographic
      (HPLC) - photodiode array (PDA) detection method to quantitate five flavonol
      components as markers; rutin, quercitrin, quercetin, kaempferol and isorhamnetin
      for use in the quality control of Ginkgo biloba dosage forms. METHODS: Separation
      was achieved using a minibore Phenomenex Luna 5microm C(18) (2) column with
      dimensions 250 x 2.00mm at 45 degrees C with a one step linear gradient using
      acetonitrile:formic acid (0.3%) at a flow rate of 0.4ml/min. RESULTS: The limits
      of quantitation for the flavonols were 2.76, 0.77, 1.11, 1.55 and 1.03microg/ml
      for rutin, quercitrin, quercetin, kaempferol and isorhamnetin, respectively. This
      method is linear over concentration ranges of 3-26microg/ml for all flavonols.
      Recoveries for rutin, quercitrin and kaempferol were above 94% while quercetin
      and isorhamnetin had average recoveries of 83% and 76%, respectively. Intraday
      precision did not exceed 6% and with-in day precision was better than 12% for all
      compounds. CONCLUSION: A suitable method was developed to identify and quantitate
      five relevant flavonol marker compounds and was successfully used to assay some
      commercially available solid oral dosage forms of Ginkgo biloba .

PMID- 15576010
TI  - Alteration of rat hepatic glycogen phosphorylase and phosphoenolpyruvate
      carboxykinase activities by Satureja khuzestanica Jamzad essential oil.
AB  - PURPOSE: Regarding reported antidiabetic effect of Satureja khuzestanica
      essential oil (SKEO) and important role of liver on body glucose metabolism by
      glycogenolysis and gluconeogenesis, we were interested to examine effect of SKEO
      treatment on rat hepatic key enzymes of glycogenolysis and gluconeogenesis in
      vivo. METHODS: Effective antidiabetic dose of SKEO (1000 ppm) was administered to
      rats through drinking water for 2 weeks. After 18 hours fasting post treatment
      under general anesthesia, the liver was removed by transverse abdominal incision
      and perfused with cold 0.9% saline and kept frozen at -70 degrees C until
      homogenized. The activities of the key enzymes glycogen phosphorylase (GP) and
      phosphoenolpyruvate carboxykinase (PEPKC) were analyzed in the homogenate. Blood
      sample was taken by cardiac puncture for glucose assay. RESULTS: SKEO treatment
      did not affect blood glucose concentrations but decreased hepatic PEPCK activity
      by 26% (P<0.01) of control and increased hepatic GP by 24% (P<0.01) of control.
      CONCLUSION: Disturbance of hepatic glucose metabolism is proposed as a mechanism
      of antidiabetic action of SKEO which could be in relation with antioxidant
      property of this plant.

PMID- 15576011
TI  - Artificial cell microcapsule for oral delivery of live bacterial cells for
      therapy: design, preparation, and in-vitro characterization.
AB  - PURPOSE: Bacterial cells can be engineered to synthesize a wide array of disease
      modifying substrates such as cytokines, vaccines and antibodies; however, their
      use as an orally delivered therapeutic is limited by poor gastrointestinal (GI)
      survival and instigation of immunogenic response. Artificial cell microcapsules
      have been well studied as a means to overcome such problems, however, presently
      obtainable microcapsules have limitations. This study summarizes a novel
      microcapsule design specifying its preparation and GI stability in-vitro. METHOD:
      Multilayer APPPA microcapsules were designed, prepared and characterized in-vitro
      for bacterial cell oral delivery using Lactobacillus reuteri cells as a model.
      Microcapsule structural integrity, mechanical stability, and GI survival studies
      were performed in simulated gastric (SGF) and intestinal (SIF) fluids in various
      pH conditions at 37.2 degrees C and compared with presently available
      alginate/poly-l-lysine/alginate (APA) microcapsules. HPLC was used for the
      microcapsule membrane permeability study. RESULTS: Results show that APPPA
      microcapsules can be prepared for bacterial cell encapsulation and are stable in
      simulated GI conditions. No microcapsule damage was reported when exposed to SGF
      and SIF for 12 hours at 250 rpm mechanical shaking at 37.2 degrees C. In
      addition, 93.2+/-2.3% and 98.9+/-0.6% of microcapsules were undamaged after 24
      hours in SGF and SIF respectively. Microcapsule pH stability results show that
      92.8+/-3.1% of microcapsules remained intact at pH 1, 3, 5, and 7 and no damage
      was observed at pH 9.0 when challenged for 24 hours. When exposed for 3 hours
      with 250 rpm shaking at 37.2 degrees C, no damage of the microcapsules in SGF and
      SIF at pH, 1,3,5,7, and 9 was observed. Compared to APA microcapsules, APPPA
      membranes showed superior GI stability and permeability for cell encapsulation.
      CONCLUSION: Novel APPPA microcapsules have superior features for oral delivery of
      live bacterial cells and they can be used for various clinical applications.
      However, further study such as membrane permeability, cytotoxicity, immune
      protection capacity, and suitability for live bacterial cell oral delivery in
      vivo is required.

PMID- 15576012
TI  - In vitro studies on guar gum based formulation for the colon targeted delivery of
      Sennosides.
AB  - PURPOSE: The objective of the present study is to develop colon targeted drug
      delivery systems for sennosides using guar gum as a carrier. METHODS: Matrix
      tablets containing various proportions of guar gum were prepared by wet
      granulation technique using starch paste as a binder. The tablets were evaluated
      for content uniformity and in vitro drug release study as per BP method. T(50) %
      value from the dissolution studies was taken for selecting the best formulation.
      RESULTS: Guar gum matrix tablets released 4-18% sennosides in the physiological
      environment of gastrointestinal tract depending on the proportion of the guar gum
      used in the formulation. The matrix tablets containing 50% of guar gum were found
      to be suitable for targeting of sennosides for local action in the colon.
      Compared to tablets having 30% and 40% of guar gum, those with 50% guar gum gave
      better T(50)% (11.7 h) le and fewer amounts (5-8%) of drug release in upper GIT.
      These tablets with 50% guar gum released 43% and 96% sennosides with and without
      rat caecal fluids. This suggests the susceptibility of matrix to the colonic
      micro flora. The similarity factor (f2 value) for drug release with and without
      rat caecal fluids was found to be less than 30. When hydroxy propyl
      methylcellulose phthalate (10%) was used as a coat material on the matrix
      tablets, the initial loss of 5-8% sennosides in stomach could be completely
      averted. These tablets showed no change in physical appearance, content and
      dissolution profile upon storage at 45 degrees C / 75% relative humidity for 3
      months. CONCLUSION: The results of our study indicates that matrix tablets
      containing 50% guar gum and coated with 10% hydroxy propyl methylcellulose
      phthalate are most suitable for drugs like sennosides which are mainly active in
      the lower GIT.

PMID- 15576013
TI  - COX-2 selective inhibitors cardiac toxicity: getting to the heart of the matter.
AB  - On September 30, 2004, Merck and Co. voluntary withdrew rofecoxib (Vioxx) from
      the market due to increased risk of cardiovascular events associated with the
      drug. This raised some issues. It is unclear whether the cardiac toxicities
      associated with rofecoxib isare due to its high COX-2 selectivity. Rofecoxib is
      the most specific COX-2 inhibitor among the first generation of the class, i.e.,
      negligible COX-1 inhibitory effect. In addition to the gastrointestinal side
      effects, COX-1 inhibition is known to offer cardioprotection. This is one of the
      main present indications of aspirin-like drugs. It is plausible that the COX-2
      inhibition is associated with altered homeostasis that is compensated with the
      cardioprotection effect of COX-1 inhibition that patients receive either through
      the less COX-2 selectivity of other NSAIDs or through co-administration of low
      dose aspirin. In addition, the cardiac toxicity of rofecoxib could be due to its
      unique chemical structure, its pharmacokinetics and tissue distribution, and/or
      the presence of toxic metabolites. Nevertheless, one cannot ignore the public
      need for NSAIDs with less gastrointestinal side effects than the traditional
      drugs. However, based on some available indirect evidence, and unless more clear
      cut data become available, the use of highly COX-2 selective NSAIDs without the
      use of a suitable COX-1 inhibitor, (e.g., low dose aspirin) may be best avoided.
      This may be particularly relevant to the chronic use of these drugs.

PMID- 15576014
TI  - Formulation of sustained - release lithium carbonate matrix tablets: influence of
      hydrophilic materials on the release rate and in vitro-in vivo evaluation.
AB  - PURPOSE: Conventional lithium carbonate (LC) tablets not only produce rapid and
      relatively high peak blood levels resulting in adverse effects but also should be
      administered 3 to 4 times daily. These drawbacks can be overcome by designing a
      suitable sustained-release LC preparation. METHODS: Sustained-release matrix
      tablets containing 450 mg LC were developed using different types and ratios of
      polymers including carbopol (CP), Na carboxymethylcellulose (Na CMC) and
      hydroxypropylmethylcellulose (HPMC). The tablets were prepared by either direct
      compression or wet granulation. In vitro and in vivo, newly formulated sustained
      release LC tablets were compared with sustained-release commercial tablet
      (Eskalith CR). In vivo studies were conducted in nine healthy subjects in a cross
      over design, with a 3 3 Latin square sequence. Pharmacokinetic parameters were
      estimated using classical methods. RESULTS: The matrix tablets containing 15% CP
      exhibited suitable release kinetics and uniform absorption characteristics
      comparable to that of Eskalith CR. In vivo, this formulation produced a smooth
      and extended absorption phase very much similar to that of Eskalith CR with the
      identical elimination half-life and extent of absorption. CONCLUSION: In vitro
      release studies demonstrated that the releases of LC from all formulated
      sustained matrix tablets were generally sustained. Na CMC, CP, and HPMC can,
      therefore, be used to modify release rates of LC in hydrophilic matrix tablets.
      The sustained release behavior of tablets containing 15% CP prevents high peak
      blood levels in man and could be given twice daily to promote patient compliance
      during maintenance therapy.

PMID- 15576015
TI  - A pilot study to evaluate the pharmacokinetics of sibutramine in healthy subjects
      under fasting and fed conditions.
AB  - PURPOSE: The purpose of this study was to characterize the food effect on the
      pharmacokinetics of sibutramine and its pharmacologically active metabolites.
      METHODS: This was an open label, single dose, crossover study completed by six
      healthy males. A single dose of sibutramine 15 mg was administered orally under
      fasting and fed conditions. Plasma concentrations of sibutramine and its
      metabolites were determined by LC/MS/MS: Non-compartmental pharmacokinetics and
      statistical analysis were performed using SAS. RESULTS: The food intake increased
      significantly AUCs and C(max) of sibutramine and its M1 metabolite, but did not
      affect M2 metabolite. When sibutramine was administered with food, the T(max) was
      delayed by 2 to 4 hours for sibutramine, M1 and M2 metabolites as stated in the
      literature. CONCLUSIONS: The results of this study indicate that sibutramine is
      measurable using a sensitive bioanalytical method. In contrast with what is
      reported in the product monograph, this study demonstrated that the
      bioavailability of sibutramine and M1 metabolite was significantly increased with
      administration with food. The results confirmed lack of food effect on the
      pharmacokinetics of M2 metabolite. These relatively large food effect observed
      for sibutramine and M1 metabolite, could have implication for the efficacy and
      safety of the drug.

PMID- 15576016
TI  - Unaffordable drug prices: the major cause of non-compliance with hypertension
      medication in Ghana.
AB  - PURPOSE: The prevalence of hypertension is increasing in Ghana. In addition
      hypertension has been identified as the most common cause of heart failure,
      stroke, chronic renal disease and spontaneous sudden deaths in Ghana. A major
      concern arising from this increasing hypertension prevalence is that many
      patients in this relatively poor country find it difficult to afford the standard
      hypertension medications. The purpose of this study was to evaluate access to
      hypertension medication and assess non-compliance with hypertension medication in
      Ghana. METHODS: Patient interviews were conducted on all new patients attending
      the hypertension clinic at Komfo Anokye teaching hospital between December 2001
      and April 2002. RESULTS: 93% of the interviewed patients did not comply with
      their medications. 96% of the non-compliant patients cited unaffordable drug
      prices as the main reason for non-compliance. CONCLUSIONS: Non-compliance with
      hypertension medication is a major problem in Ghana. Unaffordable drug prices
      appear the major cause. Effort should be made both locally and internationally to
      improve access to medications for chronic diseases in developing countries.

PMID- 15576017
TI  - Isoforms of serum gamma-glutamyltransferase in epileptic patients treated with
      enzyme-inducing anticonvulsant drugs.
AB  - PURPOSE: The increase of serum activity of gamma-glutamyltranferase (gammaGT)
      through the action of enzyme-inducing anticonvulsant drugs has been widely
      documented; however, the behaviour of its multiple forms and its relationship
      with the degree of enzyme induction has received little coverage. This subject is
      the major aim of our paper. METHODS: An electrophoretic study of the serum
      gammaGT isoforms was made in 90 adult epileptic patients under chronic treatment
      with phenobarbital, phenytoin and carbamazepine in polytherapy. RESULTS: A
      significant correlation was found (p<0.001) between the drug score and urinary
      excretion of D-glucaric acid (DGA) (r=0.773), total gammaGT (r=0.382), gammaGT1
      (r=0.398) and gammaGT2 (r=0.361). In a group of 11 patients with the gammaGT3
      isoforms, considered a sensitive test for cholestasis, serum activities of total
      gammaGT, gammaGT1, gammaGT2 and 5 -nucleotidase were found that were
      significantly higher than in the 79 patients without the gammaGT3 isoform
      (p<0.001); however, for the drug score and excretion of DGA, no significant
      differences were found, suggesting a similar degree of enzyme induction in both
      groups of patients. CONCLUSIONS: The presence of cholestasis, at least
      biochemically detectable in some of these patients, appears to be a factor of
      paramount importance when interpreting the effect of enzyme-inducing
      anticonvulsant drugs on serum gammaGT. This fact may contribute towards
      explaining its highly varied response to the administration of these drugs.

PMID- 15576018
TI  - Influence of the pro-inflammatory cytokines on P-glycoprotein expression and
      functionality.
AB  - PURPOSE: P-glycoprotein (P-gp) is involved in the transport of many drugs at
      different barriers with consequence in terms of drug distribution and
      elimination. The expression and activity of P-gp can be modulated by different
      factors and pathologies. The present article reviews the knowledge regarding the
      effect of pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-6, IL-2, IFNgamma)
      on the expression and the functionality of P-gp at three major sites of drug
      absorption and disposition: the liver, the blood-brain barrier, and the
      intestine. METHODS: The various methods used to study the effect of pro
      inflammatory cytokines include in vivo models (i.e. animals infected with
      Staphylococcus sp, animals injected with bacterial lipopolysaccharide or directly
      with cytokines, ...) and in vitro models (i.e. primary rat hepatocytes, human
      brain endothelial cells, ...). RESULTS: The data on P-gp expression and/or
      function may differ according to the compound used to induce inflammation.
      However, there is a general trend towards a decrease in both the expression of P
      gp (mRNA and protein) and its functionality. Transcription factors and nuclear
      receptors are probably involved in this regulation. CONCLUSION: Cytokines may
      interfere with P-gp. Hence, in pathological conditions (inflammation, infection,
      ...), the expression and functionality of P-glycoprotein may be modulated with
      consequences for drug disposition and, consequently treatment efficacy.

PMID- 15576019
TI  - Angiographic patency study of an albumin-free recombinant streptokinase
      formulation in acute myocardial infarction.
AB  - PURPOSE: Fibrinolytic therapy restores coronary patency and reduces mortality in
      patients with acute myocardial infarction. Albumin is present in most of the
      streptokinase formulation as a stabilizer but it is not known whether it plays a
      role in the product's efficacy and safety profiles. The aim of this study was to
      assess 90 minutes-coronary patency of a new albumin-free recombinant
      streptokinase (rSK) formulation. METHODS . Patients with ischemic chest pain and
      ST-segment elevation, less than 12 hours after symptoms onset, without
      contraindications for fibrinolytic therapy, were included to receive 1.5 x 10(6)
      IU of rSK in a one-hour intravenous infusion. Angiography was performed 90
      minutes after and coronary patency was classified according to the TIMI flow
      scales. RESULTS: The study enrolled 25 patients, 59.4 +/- 9.2 years-old, 88% men
      and 92% white. The mean time interval between the symptoms onset and rSK infusion
      was 3.0 +/- 2.0 hours. Patency rate (TIMI 2-3) of the infarct-related vessel was
      72% (18/25). Partial or complete ST-segment resolution was achieved in 17
      patients (68%). Hypotension and nauseas were the most frequent adverse events.
      Haemorrhage or in-hospital deaths were not reported. CONCLUSIONS: This study
      suggests that intravenous albumin-free rSK is a safe and appropriate therapy to
      get early (90-minute) coronary patency in patients with acute myocardial
      infarction.

PMID- 15576020
TI  - Effect of acidic ternary compounds on the formation of miconazole/cyclodextrin
      inclusion complexes by means of supercritical carbon dioxide.
AB  - PURPOSE: The aim of the study is to evaluate the effect of different acidic
      compounds on the inclusion of miconazole (MICO) in several cyclodextrins (CDs)
      using supercritical carbon dioxide (SCCO(2) ) processing. METHODS: Physical
      mixtures were processed by SCCO(2) at 30 MPa, 125 degrees C during 60 minutes in
      a static mode to produce inclusion complexes. The inclusion complexes were
      characterized by differential solubility, Fourier transform infrared spectroscopy
      (FT-IR) and dissolution test. RESULTS: The best inclusion yields were achieved
      with the combination of MICO base and HPgammaCD with or without acids. Maleic and
      fumaric acids influenced the MICO inclusion differently in function of their
      conformation. During the process, a miconazole salt was observed with maleic acid
      and characterized by thermal analysis and mass spectrometry. The kinetics
      inclusion followed a saturation-type shape curve. FT-IR confirmed the presence of
      genuine inclusion complexes. The complexes MICO base/HPgammaCD/(L-tartaric acid)
      enhanced the dissolution rates of MICO more than the corresponding physical
      mixtures did. Lastly, the stability study revealed that the complexes were
      stable. CONCLUSIONS: The formation of stable complexes between MICO and CDs is
      possible using SCCO(2). Moreover an acidic ternary compound is able to modify the
      formation of the complex. The inclusion complexes, which show better dissolution
      profiles than those with the corresponding physical mixtures, could lead to an
      increase of the oral bioavailability of MICO.

PMID- 15576021
TI  - Introducing a 4th dimension to protein-protein docking.

PMID- 15576022
TI  - Integrin activation in vivo and in silico.

PMID- 15576023
TI  - Nucleosome assembly: more than electric in the making?

PMID- 15576024
TI  - Chromosomal DNA replication on a protein "chip".

PMID- 15576025
TI  - Deja vu all over again: finding and analyzing protein structure similarities.
AB  - Structure comparison is a crucial aspect of structural biology today. The field
      of structure comparison is developing rapidly, with the development of new
      algorithms, similarity scores, and statistical scores. The predicted large
      increase of experimental structures and structural models made possible by high
      throughput efforts means that structural comparison and searching of structural
      databases using automated methods will become increasingly common. This Ways &
      Means article is meant to guide the structural biologist in the basics of
      structural alignment, and to provide an overview of the available software tools.
      The main purpose is to encourage users to gain some understanding of the
      strengths and limitations of structural alignment, and to take these factors into
      account when interpreting the results of different programs.

PMID- 15576026
TI  - Membrane protein crystallization in lipidic mesophases with tailored bilayers.
AB  - Monoacylglycerols have been used as bilayered hosts for growing crystals of
      membrane proteins. To date, the lipids used have had chains 16 and 18 carbon
      atoms long. We hypothesized that a shorter-chained lipid producing a thinner
      bilayer would facilitate the so-called in meso crystallization process. A 14
      carbon monoacylglycerol was chosen as the lipid with which to test the proposal.
      To be compatible with the in meso method, a cis olefinic bond was placed in its
      acyl chain at a location arrived at by rational design. The target lipid was
      synthesized and was shown to form the requisite mesophase at room temperature. In
      support of the hypothesis, it produced crystals of bacteriorhodopsin and the
      outer membrane transporter, BtuB. The latter is the first beta barrel protein to
      be crystallized by the in meso method. Protein stability in the short-chain lipid
      and how this relates to crystallogenesis are discussed.

PMID- 15576027
TI  - Complementarity of structure ensembles in protein-protein binding.
AB  - Protein-protein association is often accompanied by changes in receptor and
      ligand structure. This interplay between protein flexibility and protein-protein
      recognition is currently the largest obstacle both to our understanding of and to
      the reliable prediction of protein complexes. We performed two sets of molecular
      dynamics simulations for the unbound receptor and ligand structures of 17 protein
      complexes and applied shape-driven rigid body docking to all combinations of
      representative snapshots. The crossdocking of structure ensembles increased the
      likelihood of finding near-native solutions. The free ensembles appeared to
      contain multiple complementary conformations. These were in general not related
      to the bound structure. We suggest that protein-protein binding follows a three
      step mechanism of diffusion, free conformer selection, and refolding. This model
      combines previously conflicting ideas and is in better agreement with the current
      data on interaction forces, time scales, and kinetics.

PMID- 15576028
TI  - Conversion between three conformational states of integrin I domains with a C
      terminal pull spring studied with molecular dynamics.
AB  - We test with molecular dynamics the hypothesis that interdomain forces in
      integrins, simulated with a spring attached to the C-terminal alpha 7-helix of an
      integrin I domain, can allosterically stabilize alternative I domain
      conformations. Depending on the force applied and timecourse, in alpha(L) and
      alpha(M) I domains the beta 6-alpha 7 loop moves successively between three
      ratchet positions; i.e. from closed to intermediate, and then to open. More
      distal, linked alterations in MIDAS loops and metal coordination closely resemble
      those seen when the MIDAS becomes ligated. Simulations show that the intermediate
      state is populated over a wider range of forces for alpha(L) than alpha(M) I
      domains. Simulations with mutant I domains suggest that specific ratchet residues
      regulate conformational equilibria. Simulations with alpha(1) and alpha(2) I
      domains reveal a lack of the intermediate conformation, owing to Phe to Glu
      substitution at the second ratchet residue. The findings have important
      implications for biological regulation of integrin adhesiveness.

PMID- 15576029
TI  - The structure and function of Xenopus NO38-core, a histone chaperone in the
      nucleolus.
AB  - Xenopus NO38 is an abundant nucleolar chaperone and a member of the nucleoplasmin
      (Np) family. Here, we report high-resolution crystal structures of the N-terminal
      domain of NO38, as a pentamer and a decamer. As expected, NO38 shares the Np
      family fold. In addition, NO38- and Np-core pentamers each use highly conserved
      residues and numerous waters to form their respective decamers. Further studies
      show that NO38 and Np each bind equal amounts of the four core histones. However,
      NO38 prefers the (H3-H4)(2) tetramer, while Np probably prefers H2A-H2B dimers.
      We also show that NO38 and Np will each bind noncognate histones when the
      preferred partner is absent. We suggest that these chaperones must form decamers
      in order to bind histones and differentiate between histone tetramers and dimers.
      When taken together, these data imply that NO38 may function as a histone
      chaperone in the nucleolus.

PMID- 15576030
TI  - New insights into FAK signaling and localization based on detection of a FAT
      domain folding intermediate.
AB  - Mounting evidence suggests that the focal adhesion targeting (FAT) domain, an
      antiparallel four-helix bundle, exists in alternative conformations that may
      modulate phosphorylation, ligand binding, and the subcellular localization of
      focal adhesion kinase (FAK). In order to characterize the conformational dynamics
      of the FAT domain, we have developed a novel method for reconstructing the
      folding pathway of the FAT domain by using discrete molecular dynamics (DMD)
      simulations, with free energy constraints derived from NMR hydrogen exchange
      data. The DMD simulations detect a folding intermediate, in which a cooperative
      unfolding event causes helix 1 to lose helical character while separating from
      the helix bundle. The conformational dynamic features of helix 1 in the
      intermediate state of the FAT domain are likely to facilitate Y926
      phosphorylation, yet interfere with paxillin binding. The presence of this
      intermediate state in vivo may promote FAK signaling via the ERK/MAPK pathway and
      by release of FAK from focal adhesions.

PMID- 15576031
TI  - Structural and functional properties of the human notch-1 ligand binding region.
AB  - We present NMR structural and dynamics analysis of the putative ligand binding
      region of human Notch-1, comprising EGF-like domains 11-13. Functional integrity
      of an unglycosylated, recombinant fragment was confirmed by calcium-dependent
      binding of tetrameric complexes to ligand-expressing cells. EGF modules 11 and 12
      adopt a well-defined, rod-like orientation rigidified by calcium. The interdomain
      tilt is similar to that found in previously studied calcium binding EGF pairs,
      but the angle of twist is significantly different. This leads to an extended
      double-stranded beta sheet structure, spanning the two EGF modules. Based on the
      conservation of residues involved in interdomain hydrophobic packing, we propose
      this arrangement to be prototypical of a distinct class of EGF linkages. On this
      premise, we have constructed a model of the 36 EGF modules of the Notch
      extracellular domain that enables predictions to be made about the general role
      of calcium binding to this region.

PMID- 15576032
TI  - Molecular mechanism for regulation of the human mitochondrial branched-chain
      alpha-ketoacid dehydrogenase complex by phosphorylation.
AB  - The human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex
      (BCKDC) is a 4 MDa macromolecular machine comprising three catalytic components
      (E1b, E2b, and E3), a kinase, and a phosphatase. The BCKDC overall activity is
      tightly regulated by phosphorylation in response to hormonal and dietary stimuli.
      We report that phosphorylation of Ser292-alpha in the E1b active site channel
      results in an order-to-disorder transition of the conserved phosphorylation loop
      carrying the phosphoryl serine. The conformational change is triggered by steric
      clashes of the phosphoryl group with invariant His291-alpha that serves as an
      indispensable anchor for the phosphorylation loop through bound thiamin
      diphosphate. Phosphorylation of Ser292-alpha does not severely impede the E1b
      dependent decarboxylation of alpha-ketoacids. However, the disordered loop
      conformation prevents phosphorylated E1b from binding the E2b lipoyl-bearing
      domain, which effectively shuts off the E1b-catalyzed reductive acylation
      reaction and therefore completely inactivates BCKDC. This mechanism provides a
      paradigm for regulation of mitochondrial alpha-ketoacid dehydrogenase complexes
      by phosphorylation.

PMID- 15576033
TI  - Understanding the selectivity of genistein for human estrogen receptor-beta using
      X-ray crystallography and computational methods.
AB  - We present X-ray crystallographic and molecular modeling studies of estrogen
      receptors-alpha and -beta complexed with the estrogen receptor-beta-selective
      phytoestrogen genistein, and coactivator-derived NR box peptides containing an
      LXXLL motif. We demonstrate that the ligand binding mode is essentially identical
      when genistein is bound to both isoforms, despite the considerably weaker
      affinity of this ligand for estrogen receptor-alpha. In addition, we examine
      subtle differences between binding site residues, providing an explanation for
      why genistein is modestly selective for the beta isoform. To this end, we also
      present the results of quantum chemical studies and thermodynamic arguments that
      yield insight to the nature of the interactions leading to estrogen receptor-beta
      selectivity. The importance of our analysis to structure-based drug design is
      discussed.

PMID- 15576034
TI  - Structural and thermodynamic analysis of human PCNA with peptides derived from
      DNA polymerase-delta p66 subunit and flap endonuclease-1.
AB  - Human Proliferating Cellular Nuclear Antigen (hPCNA), a member of the sliding
      clamp family of proteins, makes specific protein-protein interactions with DNA
      replication and repair proteins through a small peptide motif termed the PCNA
      interacting protein, or PIP-box. We solved the structure of hPCNA bound to PIP
      box-containing peptides from the p66 subunit of the human replicative DNA
      polymerase-delta (452-466) at 2.6 A and of the flap endonuclease (FEN1) (331-350)
      at 1.85 A resolution. Both structures demonstrate that the pol-delta p66 and FEN1
      peptides interact with hPCNA at the same site shown to bind the cdk-inhibitor
      p21(CIP1). Binding studies indicate that peptides from the p66 subunit of the pol
      delta holoenzyme and FEN1 bind hPCNA from 189- to 725-fold less tightly than
      those of p21. Thus, the PIP-box and flanking regions provide a small docking
      peptide whose affinities can be readily adjusted in accord with biological
      necessity to mediate the binding of DNA replication and repair proteins to hPCNA.

PMID- 15576035
TI  - Phage like it HOT: solution structure of the bacteriophage P1-encoded HOT
      protein, a homolog of the theta subunit of E. coli DNA polymerase III.
AB  - DNA polymerase III, the main replicative polymerase of E. coli, contains a small
      subunit, theta, that binds to the epsilon proofreading subunit and appears to
      enhance the enzyme's proofreading function--especially under extreme conditions.
      It was recently discovered that E. coli bacteriophage P1 encodes a theta homolog,
      named HOT. The (1)H-(15)N HSQC spectrum of HOT exhibits more uniform intensities
      and less evidence of conformational exchange than that of theta; this uniformity
      facilitates a determination of the HOT solution structure by NMR. The structure
      contains three alpha helices, as reported previously for theta; however, the
      folding topology of the two proteins is very different. Residual dipolar coupling
      measurements on labeled theta support the conclusion that it is structurally
      homologous with HOT. As judged by CD measurements, the melting temperature of HOT
      was 62 degrees C, compared to 56 degrees C for theta, consistent with other data
      suggesting greater thermal stability of the HOT protein.

PMID- 15576036
TI  - Structural basis for the activity of drugs that inhibit phosphodiesterases.
AB  - Phosphodiesterases (PDEs) comprise a large family of enzymes that catalyze the
      hydrolysis of cAMP or cGMP and are implicated in various diseases. We describe
      the high-resolution crystal structures of the catalytic domains of PDE4B, PDE4D,
      and PDE5A with ten different inhibitors, including the drug candidates cilomilast
      and roflumilast, for respiratory diseases. These cocrystal structures reveal a
      common scheme of inhibitor binding to the PDEs: (i) a hydrophobic clamp formed by
      highly conserved hydrophobic residues that sandwich the inhibitor in the active
      site; (ii) hydrogen bonding to an invariant glutamine that controls the
      orientation of inhibitor binding. A scaffold can be readily identified for any
      given inhibitor based on the formation of these two types of conserved
      interactions. These structural insights will enable the design of isoform
      selective inhibitors with improved binding affinity and should facilitate the
      discovery of more potent and selective PDE inhibitors for the treatment of a
      variety of diseases.

PMID- 15576037
TI  - Structure of a xanthine oxidase-related 4-hydroxybenzoyl-CoA reductase with an
      additional [4Fe-4S] cluster and an inverted electron flow.
AB  - The Mo-flavo-Fe/S-dependent heterohexameric protein complex 4-hydroxybenzoyl-CoA
      reductase (4-HBCR, dehydroxylating) is a central enzyme of the anaerobic
      degradation of phenolic compounds and belongs to the xanthine oxidase (XO) family
      of molybdenum enzymes. Its X-ray structure was established at 1.6 A resolution.
      The most pronounced difference between 4-HBCR and other structurally
      characterized members of the XO family is the insertion of 40 amino acids within
      the beta subunit, which carries an additional [4Fe-4S] cluster at a distance of
      16.5 A to the isoalloxazine ring of FAD. The architecture of 4-HBCR and
      concomitantly performed electron transfer rate calculations suggest an inverted
      electron transfer chain from the donor ferredoxin via the [4Fe-4S] cluster to the
      Mo over a distance of 55 A. The binding site of 4-hydroxybenzoyl-CoA is located
      in an 18 A long channel lined up by several aromatic side chains around the
      aromatic moiety, which are proposed to shield and stabilize the postulated
      radical intermediates during catalysis.

PMID- 15576038
TI  - Crystal structure of a FYVE-type zinc finger domain from the caspase regulator
      CARP2.
AB  - The caspase-associated ring proteins (CARP1 and CARP2) are distinguished from
      other caspase regulators by the presence of a FYVE-type zinc finger domain. FYVE
      type domains are divided into two known classes: FYVE domains that specifically
      bind to phosphatidylinositol 3-phosphate in lipid bilayers and FYVE-related
      domains of undetermined function. Here, we report the crystal structure of the N
      terminal region of CARP2 (44-139) including the FYVE-type domain and its
      associated helical bundle at 1.7 A resolution. The structure reveals a cramped
      phosphoinositide binding pocket and a blunted membrane insertion loop. These
      structural features indicate that the domain is not optimized to bind to
      phosphoinositides or insert into lipid bilayers. The CARP2 FYVE-like domain thus
      defines a third subfamily of FYVE-type domains that are functionally and
      structurally distinct. Structural analyses provide insights into the possible
      function of this unique subfamily of FYVE-type domains.

PMID- 15576039
TI  - A putative mechanism for downregulation of the catalytic activity of the EGF
      receptor via direct contact between its kinase and C-terminal domains.
AB  - Tyrosine kinase receptors of the EGFR family play a significant role in vital
      cellular processes and in various cancers. EGFR members are unique among kinases,
      as the regulatory elements of their kinase domains are constitutively ready for
      catalysis. Nevertheless, the receptors are not constantly active. This apparent
      paradox has prompted us to seek mechanisms of regulation in EGFR's cytoplasmic
      domain that do not involve conformational changes of the kinase domain. Our
      computational analyses, based on the three-dimensional structure of EGFR's kinase
      domain suggest that direct contact between the kinase and a segment from the C
      terminal regulatory domains inhibits enzymatic activity. EGFR activation would
      then involve temporal dissociation of this stable complex, for example, via
      ligand-induced contact formation between the extracellular domains, leading to
      the reorientation of the transmembrane and intracellular domains. The model
      provides an explanation at the molecular level for the effects of several cancer
      causing EGFR mutations.

PMID- 15576040
TI  - The Euromit meetings: an international platform for the understanding and combat
      of mitochondrial disease.

PMID- 15576041
TI  - Mitochondrial medicine.
AB  - After reviewing the history of mitochondrial diseases, I follow a genetic
      classification to discuss new developments and old conundrums. In the field of
      mitochondrial DNA (mtDNA) mutations, I argue that we are not yet scraping the
      bottom of the barrel because: (i) new mtDNA mutations are still being discovered,
      especially in protein-coding genes; (ii) the pathogenicity of homoplasmic
      mutations is being revisited; (iii) some genetic dogmas are chipped but not
      broken; (iv) mtDNA haplotypes are gaining interest in human pathology; (v)
      pathogenesis is still largely enigmatic. In the field of nuclear DNA (nDNA)
      mutations, there has been good progress in our understanding of disorders due to
      faulty intergenomic communication. Of the genes responsible for multiple
      deletions and depletion of mtDNA, mutations in POLG have been associated with a
      great variety of clinical phenotypes in humans and to precocious aging in mice.
      Novel pathogenetic mechanisms include alterations in the lipid milieu of the
      inner mitochondrial membrane and mutations in genes controlling mitochondrial
      motility, fission, and fusion.

PMID- 15576042
TI  - The epidemiology of mitochondrial disorders--past, present and future.
AB  - A number of epidemiological studies of mitochondrial disease have been carried
      out over the last decade, clearly demonstrating that mitochondrial disorders are
      far more common than was previously accepted. This review summarizes current
      knowledge of the prevalence of human mitochondrial disorders--data that has
      important implications for the provision of health care and adequate resources
      for research into the pathogenesis and treatment of these disorders.

PMID- 15576043
TI  - Biochemical and molecular diagnosis of mitochondrial respiratory chain disorders.
AB  - Biochemical diagnosis of mitochondrial respiratory chain disorders requires
      caution to avoid misdiagnosis of secondary enzyme defects, and can be improved by
      the use of conservative diagnostic criteria. Pathogenic mutations causing
      mitochondrial disorders have now been identified in more than 30 mitochondrial
      DNA (mtDNA) genes encoding respiratory chain subunits, ribosomal- and t-RNAs.
      mtDNA mutations appear to be responsible for most adult patients with
      mitochondrial disease and approximately a quarter of paediatric patients. A
      family history suggesting maternal inheritance is the exception rather than the
      norm for children with mtDNA mutations, many of whom have de novo mutations.
      Prenatal diagnosis and pre-implantation genetic diagnosis can be offered to some
      women at risk of transmitting a mtDNA mutation, particularly those at lower
      recurrence risk. Mutations in more than 30 nuclear genes, including those
      encoding for respiratory chain subunits and assembly factors, have now been shown
      to cause mitochondrial disorders, creating difficulties in prioritising which
      genes should be studied by mutation analysis in individual patients. A number of
      approaches offer promise to guide the choice of candidate genes, including Blue
      Native-PAGE immunoblotting and microarray expression analysis.

PMID- 15576044
TI  - Molecular diagnostics of mitochondrial disorders.
AB  - The mitochondrial respiratory chain (RC) results from the expression of both
      mitochondrial and nuclear genes. The number of disease-causing mutations in
      nuclear genes is steadily growing and mitochondrial DNA (mtDNA) deletions and
      mutations account for no more than 15-20% of pediatric patients. Unfortunately,
      the disease-causing mutations have been identified for only a small number of
      patients. Thus, elucidating the genetic bases of RC is both essential for genetic
      diagnosis of patients and for fundamental knowledge of these disorders. The
      molecular diagnostics of mitochondrial disorders come under both genetic
      diagnosis and research. Indeed, identification of a new gene in a specific
      patient allows to perform genetic diagnosis in other families and identification
      of mutations in already known disease-causing genes allows to constitute a cohort
      of patients for further functional studies. Thus, elucidating the genetic bases
      of RC deficiency is an essential task that needs the use of several appropriate
      strategies. Fine phenotypage of patients and candidate gene screening is the
      first step for the constitution of a well-characterized cohort of patients.
      Genetic mapping has to be used in large families. This approach is greatly
      enhanced in the case of consanguineous families. The consanguinity of the parents
      should also lead to test genetic markers surrounding the gene loci rather than to
      directly sequence several candidate genes. However, the main problem is
      encountered in the cases of sporadic cases for which no genetic approaches can be
      developed. In these cases, functional complementation by human chromosomes or
      cDNA is the only presently available strategy.

PMID- 15576045
TI  - Clinical and molecular findings in children with complex I deficiency.
AB  - Isolated complex I deficiency, the most frequent OXPHOS disorder in infants and
      children, is genetically heterogeneous. Mutations have been found in seven
      mitochondrial DNA (mtDNA) and eight nuclear DNA encoded subunits, respectively,
      but in most of the cases the genetic basis of the biochemical defect is unknown.
      We analyzed the entire mtDNA and 11 nuclear encoded complex I subunits in 23
      isolated complex I-deficient children, classified into five clinical groups:
      Leigh syndrome, progressive leukoencephalopathy, neonatal cardiomyopathy, severe
      infantile lactic acidosis, and a miscellaneous group of unspecified
      encephalomyopathies. A genetic definition was reached in eight patients (35%).
      Mutations in mtDNA were found in six out of eight children with Leigh syndrome,
      indicating a prevalent association between this phenotype and abnormalities in ND
      genes. In two patients with leukoencephalopathy, homozygous mutations were
      detected in two different nuclear-encoded complex I genes, including a novel
      transition in NDUFS1 subunit. In addition to these, a child affected by
      mitochondrial encephalomyopathy had heterozygous mutations in NDUFA8 and NDUFS2
      genes, while another child with neonatal cardiomyopathy had a complex
      rearrangement in a single NDUFS7 allele. The latter cases suggest the possibility
      of unconventional patterns of inheritance in complex I defects.

PMID- 15576046
TI  - The transcription machinery in mammalian mitochondria.
AB  - Initiation of transcription at mitochondrial promoters in mammalian cells
      requires the simultaneous presence of a monomeric mitochondrial RNA polymerase,
      mitochondrial transcription factor A, and either transcription factor B1 or B2.
      We here review recent progress in our understanding of how these basal factors
      cooperate in the initiation and regulation of mitochondrial transcription. We
      describe the evolutionary origin of individual transcription factors and discuss
      how these phylogenetic relationships may facilitate a molecular understanding of
      the mitochondrial transcription machinery.

PMID- 15576047
TI  - Defects in the biosynthesis of mitochondrial heme c and heme a in yeast and
      mammals.
AB  - Defects in heme biosynthesis have been associated with a large number of
      diseases, but mostly recognized in porphyrias, which are neurovisceral or
      cutaneous disorders caused by the accumulation of biosynthetic intermediates.
      However, defects in the maturation of heme groups that are part of the oxidative
      phosphorylation system are now also recognized as important causes of disease.
      The electron transport chain contains heme groups of the types a, b and c, all of
      which are directly involved in electron transfer reactions. In this article, we
      review the effect of mutations in enzymes involved in the maturation of heme a
      (the prosthetic group of cytochrome c oxidase) and heme c (the prosthetic group
      of cytochrome c) both in yeast and in humans. COX10 and COX15 are two genes,
      initially identified in Saccharomyces cerevisiae that have been found to cause
      infantile cytochrome c oxidase deficiency in humans. They participate in the
      farnesylation and hydroxylation of heme b, steps that are necessary for the
      formation of heme a, the prosthetic group required for cytochrome oxidase
      assembly and activity. Deletion of the cytochrome c heme lyase gene in a single
      allele has also been associated with a human disease, known as Microphthalmia
      with Linear Skin defects (MLS) syndrome. The cytochrome c heme lyase is necessary
      to covalently attach the heme group to the apocytochrome c polypeptide. The
      production of mouse models recapitulating these diseases is providing novel
      information on the pathogenesis of clinical syndromes.

PMID- 15576048
TI  - Molecular genetics of complex I-deficient Chinese hamster cell lines.
AB  - The work from our laboratory on complex I-deficient Chinese hamster cell mutants
      is reviewed. Several complementation groups with a complete defect have been
      identified. Three of these are due to X-linked mutations, and the mutated genes
      for two have been identified. We describe null mutants in the genes for the
      subunits MWFE (gene: NDUFA1) and ESSS. They represent small integral membrane
      proteins localized in the Ialpha (Igamma) and Ibeta subcomplexes, respectively
      [J. Hirst, J. Carroll, I.M. Fearnley, R.J. Shannon, J.E. Walker. The nuclear
      encoded subunits of complex I from bovine heart mitochondria. Biochim. Biophys.
      Acta 1604 (7-10-2003) 135-150.]. Both are absolutely essential for assembly and
      activity of complex I. Epitope-tagged versions of these proteins can be expressed
      from a poly-cistronic vector to complement the mutants, or to be co-expressed
      with the endogenous proteins in other hamster cell lines (mutant or wild type),
      or human cells. Structure-function analyses can be performed with proteins
      altered by site-directed mutagenesis. A cell line has been constructed in which
      the MWFE subunit is conditionally expressed, opening a window on the kinetics of
      assembly of complex I. Its targeting, import into mitochondria, and orientation
      in the inner membrane have also been investigated. The two proteins have recently
      been shown to be the targets for a cAMP-dependent kinase [R. Chen, I.M. Fearnley,
      S.Y. Peak_Chew, J.E. Walker. The phosphorylation of subunits of complex I from
      bovine heart mitochondria. J. Biol. Chem. xx (2004) xx-xx.]. The epitope-tagged
      proteins can be cross-linked with other complex I subunits.

PMID- 15576049
TI  - Respiratory chain defects: what do we know for sure about their consequences in
      vivo?
AB  - The function and the structure of mitochondria have been the subject of intensive
      research since the discovery of these organelles. Yet, the investigation of
      patients with mitochondrial disease reveals that we do not understand a large
      part of the underlying pathogenic processes. This has disastrous consequences in
      terms of the therapy possibly proposed to the patients and their family. An
      attempt is made in this short review to question our present ideas on the
      potential consequences of mitochondrial dysfunctions and to enlighten new
      observations which might be valuable in the understanding of the physiopathology
      of these diseases.

PMID- 15576050
TI  - Viral proteins targeting mitochondria: controlling cell death.
AB  - Mitochondrial membrane permeabilization (MMP) is a critical step regulating
      apoptosis. Viruses have evolved multiple strategies to modulate apoptosis for
      their own benefit. Thus, many viruses code for proteins that act on mitochondria
      and control apoptosis of infected cells. Viral proapoptotic proteins translocate
      to mitochondrial membranes and induce MMP, which is often accompanied by
      mitochondrial swelling and fragmentation. From a structural point of view, all
      the viral proapoptotic proteins discovered so far contain amphipathic alpha
      helices that are necessary for the proapoptotic effects and seem to have pore
      forming properties, as it has been shown for Vpr from human immunodeficiency
      virus-1 (HIV-1) and HBx from hepatitis B virus (HBV). In contrast, antiapoptotic
      viral proteins (e.g., M11L from myxoma virus, F1L from vaccinia virus and BHRF1
      from Epstein-Barr virus) contain mitochondrial targeting sequences (MTS) in their
      C-terminus that are homologous to tail-anchoring domains. These domains are
      similar to those present in many proteins of the Bcl-2 family and are responsible
      for inserting the protein in the outer mitochondrial membrane leaving the N
      terminus of the protein facing the cytosol. The antiapoptotic proteins K7 and K15
      from avian encephalomyelitis virus (AEV) and viral mitochondria inhibitor of
      apoptosis (vMIA) from cytomegalovirus are capable of binding host-specific
      apoptosis-modulatory proteins such as Bax, Bcl-2, activated caspase 3, CAML, CIDE
      B and HAX. In conclusion, viruses modulate apoptosis at the mitochondrial level
      by multiple different strategies.

PMID- 15576051
TI  - Mitochondrial disease in flies.
AB  - The Drosophila mutant technical knockout (tko), affecting the mitochondrial
      protein synthetic apparatus, exhibits respiratory chain deficiency and a
      phenotype resembling various features of mitochondrial disease in humans
      (paralytic seizures, deafness, developmental retardation). We are using this
      mutant to analyse the cellular and genomic targets of mitochondrial dysfunction,
      and to identify ways in which the phenotype can be alleviated. Transgenic
      expression of wild-type tko in different patterns in the mutant background
      reveals critical times and cell-types for production of components of the
      mitochondrial disease-like phenotype. Mitochondrial bioenergy deficit during the
      period of maximal growth, as well as in specific parts of the nervous system,
      appears to be most deleterious. Inbreeding of tko mutant lines results in a
      systematic improvement in all phenotypic parameters tested. The resulting sub
      lines can be used for genetic mapping and transcriptomic analysis, revealing
      clues as to the genes and pathways that can modify mitochondrial disease-like
      phenotypes in a model metazoan.

PMID- 15576052
TI  - Application of the yeast Yarrowia lipolytica as a model to analyse human
      pathogenic mutations in mitochondrial complex I (NADH:ubiquinone oxidoreductase).
AB  - While diagnosis and genetic analysis of mitochondrial disorders has made
      remarkable progress, we still do not understand how given molecular defects are
      correlated to specific patterns of symptoms and their severity. Towards resolving
      this dilemma for the largest and therefore most affected respiratory chain
      enzyme, we have established the yeast Yarrowia lipolytica as a eucaryotic model
      system to analyse respiratory chain complex I. For in vivo analysis, eYFP protein
      was attached to the 30-kDa subunit to visualize complex I and mitochondria.
      Deletions strains for nuclear coded subunits allow the reconstruction of patient
      alleles by site-directed mutagenesis and plasmid complementation. In most of the
      pathogenic mutations analysed so far, decreased catalytic activities, elevated
      K(M) values, and/or elevated I(50) values for quinone-analogous inhibitors were
      observed, providing plausible clues on the pathogenic process at the molecular
      level. Leigh mutations in the 49-kDa and PSST homologous subunits are found in
      regions that are at the boundaries of the ubiquinone-reducing catalytic core.
      This supports the proposed structural model and at the same time identifies novel
      domains critical for catalysis. Thus, Y. lipolytica is a useful lower eucaryotic
      model that will help to understand how pathogenic mutations in complex I
      interfere with enzyme function.

PMID- 15576053
TI  - Focused proteomics: towards a high throughput monoclonal antibody-based
      resolution of proteins for diagnosis of mitochondrial diseases.
AB  - The availability of monoclonal antibodies (mAbs) against the proteins of the
      oxidative phosphorylation chain (OXPHOS) and other mitochondrial components
      facilitates the analysis and ultimately the diagnosis of mitochondrially related
      diseases. mAbs against each of the five complexes and pyruvate dehydrogenase
      (PDH) are the basis of a rapid and simple immunocytochemical approach [Hanson,
      B.J., Capaldi, R.A., Marusich, M.F. and Sherwood, S.W., J. Histochem. Cytochem.
      50 (2002) 1281-1288]. This approach can be used to detect if complexes have
      altered assembly in mitochondrial disease due to mutations in nuclear encoded
      genes, such as in Leigh's disease, or in mitochondrially encoded genes, e.g.,
      MELAS. Other mAbs have recently been obtained that can immunocapture each of the
      five OXPHOS complexes, PDH and the adenine nucleotide translocase (ANT) from very
      small amounts of tissue such as that obtained from cell culture or needle
      biopsies from patients. When adapted to a 96-well plate format, these mAbs allow
      measurement of the specific activity of each of the mitochondrial components
      individually and analysis of their subunit composition and state of
      posttranslational modification. The immunocapture protocol should be useful not
      only in the analysis of genetic mitochondrial diseases but also in evaluating and
      ultimately diagnosing late-onset mitochondrial disorders including Parkinson's
      disease, Alzheimer's disease, and late-onset diabetes, which are thought to
      result from accumulated oxidative damage to mitochondrial proteins such as the
      OXPHOS chain.

PMID- 15576054
TI  - Shaping the mitochondrial proteome.
AB  - Mitochondria are eukaryotic organelles that originated from a single bacterial
      endosymbiosis some 2 billion years ago. The transition from the ancestral
      endosymbiont to the modern mitochondrion has been accompanied by major changes in
      its protein content, the so-called proteome. These changes included complete loss
      of some bacterial pathways, amelioration of others and gain of completely new
      complexes of eukaryotic origin such as the ATP/ADP translocase and most of the
      mitochondrial protein import machinery. This renewal of proteins has been so
      extensive that only 14-16% of modern mitochondrial proteome has an origin that
      can be traced back to the bacterial endosymbiont. The rest consists of proteins
      of diverse origin that were eventually recruited to function in the organelle.
      This shaping of the proteome content reflects the transformation of mitochondria
      into a highly specialized organelle that, besides ATP production, comprises a
      variety of functions within the eukaryotic metabolism. Here we review recent
      advances in the fields of comparative genomics and proteomics that are throwing
      light on the origin and evolution of the mitochondrial proteome.

PMID- 15576055
TI  - Implications of exercise training in mtDNA defects--use it or lose it?
AB  - Whether regular exercise is beneficial or should be avoided is a question
      currently unsettled in patients with heteroplasmic mitochondrial DNA (mtDNA)
      disorders of skeletal muscle. Deleterious effects of habitual physical inactivity
      superimposed upon impaired mitochondrial oxidative phosphorylation may contribute
      to varying degrees of exercise intolerance in these patients. Endurance exercise
      training is widely known to improve exercise capacity in healthy subjects and
      various chronic-disease patient populations. Although we have shown that
      beneficial physiological and biochemical responses to training increase exercise
      tolerance in patients with mtDNA defects, knowledge of the muscle adaptive
      response to endurance training within the setting of mitochondrial heteroplasmy
      remains limited. In order to determine advisability of endurance training as
      therapy, it remains to be established whether potential endurance training
      induced increases in mutant mtDNA levels may be offset by increases in absolute
      wild-type mtDNA levels, and whether chronic inactivity leads to a selective down
      regulation of wild-type mtDNA. Resistance training utilizes a different adaptive
      exercise approach to induce the transfer of normal mitochondrial templates from
      satellite cells to mature muscle fibers of patients with sporadic mtDNA
      disorders. The efficacy and safety of this approach needs to be further
      established. Our current inability to clearly advise patients to "use it or lose
      it" underscores the immediate urgency of studying the effects of exercise on
      skeletal muscle of patients with heteroplasmic mtDNA defects.

PMID- 15576056
TI  - Strategies for treating disorders of the mitochondrial genome.
AB  - Defects of the mitochondrial genome are a significant cause of disease. Patients
      suffer from a wide variety of clinical presentations, ranging from fatal
      infantile disease to mild muscle weakness. Most disorders, however, are
      characterized by inexorable progression. As mutations often cause defects in
      several components of the complexes that couple oxidative phosphorylation, this
      terminal state of oxidative metabolism cannot be readily bypassed by dietary
      means, leading to the search for novel therapies. In this article, we present the
      theory behind several concepts and report progress. We also discuss some of the
      recent difficulties encountered in the progress towards an antigenomc approach to
      treating mtDNA disorders.

PMID- 15576057
TI  - Cytokines and psychopathology: lessons from interferon-alpha.
AB  - Interferon-alpha is a potent inducer of the cytokine network and is notorious for
      causing behavioral alterations. Studies on interferon-alpha-treated patients
      reveal at least two distinct syndromes: 1) a mood/cognitive syndrome that appears
      late during interferon-alpha therapy is responsive to antidepressants and is
      associated with activation of neuroendocrine pathways and altered serotonin
      metabolism; and 2) a neurovegetative syndrome characterized by psychomotor
      slowing, and fatigue that appears early during interferon-alpha treatment is
      antidepressant nonresponsive and may be mediated by alterations in basal ganglia
      dopamine metabolism. Findings from interferon-alpha may provide important clues
      regarding the pathophysiology and treatment of cytokine-induced behavioral
      changes in medically ill patients, while also potentially modeling the
      development of neuropsychiatric symptoms in patients without medical disorders.

PMID- 15576058
TI  - Hippocampal changes and white matter lesions in early-onset depression.
AB  - BACKGROUND: Hippocampal volume reduction and increased prevalence of subcortical
      white matter lesions have been reported in late-life depression. We aimed to
      examine whether total number of subcortical white matter lesions were associated
      with reduced hippocampal volume in aged female subjects with early-onset
      depression (< 45 years) and healthy comparison subjects. METHODS: The study
      included 28 middle-aged and elderly subjects with major depression and 41 age
      matched control subjects. Hippocampal, parahippocampal gyrus, and orbitofrontal
      cortex volumes were determined using manual tracing methods. White matter lesions
      were rated from T2-weighted MRI scans using a semiquantitative classification
      scale. RESULTS: After controlling for total brain volume and age, patients had
      reduced hippocampal volume due to right hippocampal volume decrease (2.84 mL vs.
      3.12 mL, F = 16.6, p < .001). Parahippocampal and orbitofrontal volumes did not
      differ significantly between groups. Multiple linear regression analysis
      indicated that reduced hippocampal volume did not significantly correlate with
      total number of subcortical white matter lesions (t = .673, p = .518).
      CONCLUSIONS: Right hippocampal volume was reduced in aged female early-onset
      subjects with depression. Total number of subcortical white matter lesions was
      not associated with the decrease in right hippocampal volume. Our data suggest
      hippocampal involvement, independent of subcortical white matter lesions, in the
      neuropathology of early-onset depression.

PMID- 15576059
TI  - Smaller hippocampal volume in patients with recent-onset posttraumatic stress
      disorder.
AB  - BACKGROUND: Previous structural magnetic resonance (MR) research in patients with
      posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in
      patients compared with control subjects. These studies have mostly involved
      subjects who have had PTSD for a number of years, such as war veterans or adult
      survivors of childhood abuse. Patients with recent-onset PTSD have rarely been
      investigated. To our knowledge only one other study has investigated such a
      group. The aim of this study was to compare hippocampal volumes of patients with
      recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen
      patients with PTSD, recruited from an accident and emergency department, were
      compared with 11, non-trauma-exposed, healthy control subjects. Patients
      underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days).
      Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject.
      Point counting and stereology were used to measure the hippocampal and amygdala
      volume of each subject. RESULTS: Right-sided hippocampal volume was significantly
      smaller in PTSD patients than control subjects after controlling for effects of
      whole brain volume and age. Neither left nor total hippocampal volume were
      significantly smaller in the PTSD group after correction. Whole brain volume was
      also found to be significantly smaller in patients. There were no differences in
      amygdala or white matter volumes between patients and control subjects.
      CONCLUSIONS: This result replicates previous findings of smaller hippocampal
      volumes in PTSD patients, but in an underinvestigated population, suggesting that
      either smaller hippocampal volume is a predisposing factor in the development of
      PTSD or that damage occurs within months of trauma, rather than a number of
      years. Either of these two hypotheses have significant implications for the
      treatment of PTSD. For instance, if it could be shown that screening for
      hippocampal volume may, in some cases, predict those likely to develop clinical
      PTSD.

PMID- 15576060
TI  - Deficits in hippocampus-mediated Pavlovian conditioning in endogenous
      hypercortisolism.
AB  - BACKGROUND: Elevated endogenous levels of corticosteroids cause neural
      dysfunction and loss, especially within the hippocampus, as well as cognitive
      impairment in hippocampus-mediated tasks. Because Cushing's syndrome patients
      suffer from hypercortisolism, they represent a unique opportunity to study the
      impact of elevated glucocorticoids on cognitive functions. The aim of this study
      was to examine the performance of Cushing's syndrome patients on trace eyeblink
      conditioning, a cross-species, hippocampal-mediated test of learning and memory.
      METHODS: Eleven Cushing's syndrome patients and 11 healthy control subjects
      participated in an eyeblink trace conditioning test (1000-msec trace) and a task
      of declarative memory for words. Salivary cortisol was collected in both the
      patients and the control subjects, and urinary free cortisol was collected in the
      patients only. RESULTS: The patients exhibited fewer conditional responses and
      remembered fewer words, compared with the control subjects. Cortisol levels
      correlated with immediate and delayed declarative memory only. Conditional
      response correlated with delayed recall after controlling for the magnitude of
      unconditional response. CONCLUSIONS: The integrity of the hippocampus seems to be
      compromised in Cushing's syndrome patients. Trace eyeblink conditioning might be
      useful both as a clinical tool to examine changes in hippocampus function in
      Cushing's disease patients and as a translational tool of research on the impact
      of chronic exposure of glucocorticoids.

PMID- 15576061
TI  - Reduced glucocorticoid and estrogen receptor alpha messenger ribonucleic acid
      levels in the amygdala of patients with major mental illness.
AB  - BACKGROUND: The amygdala is a limbic structure involved in the stress response
      and the regulation of emotional behaviors, both of which are disrupted in
      patients with neuropsychiatric illnesses. Because glucocorticoids are mediators
      of the stress response, we hypothesized that glucocorticoid receptor (GR)
      messenger ribonucleic acid (mRNA) levels might be altered in the amygdala. We
      also hypothesized that estrogen receptor alpha (ERalpha) mRNA expression might be
      altered in the amygdala, on the basis of observed gender differences in mental
      illness. METHODS: Using quantitative film autoradiography after in situ
      hybridization with human GR and ERalpha probes, we measured mRNA levels on
      adjacent amygdala sections in four groups (n = 15 each of subjects with
      schizophrenia, major depressive disorder, and bipolar disorder, and unaffected
      control subjects) provided by the Stanley Consortium. RESULTS: We detected main
      effects of diagnosis and exposure to antidepressant medication on the levels of
      both mRNAs but no main effect of gender. Compared with control subjects, GR mRNA
      expression was reduced in the basolateral/lateral nuclei in schizophrenia and
      bipolar disorder. Estrogen receptor alpha mRNA levels were reduced in the
      basomedial nucleus in major depressive disorder and bipolar disorder.
      CONCLUSIONS: Our results support and extend previous findings describing a
      pattern of steroid hormone mRNA alterations that differs depending on which brain
      region is being examined in a given mental illness.

PMID- 15576062
TI  - Cerebral blood flow changes during script-driven imagery in police officers with
      posttraumatic stress disorder.
AB  - BACKGROUND: Functional brain imaging studies in posttraumatic stress disorder
      (PTSD) have focused mostly on war or sexual abuse victims, many of whom also had
      comorbid disorders. The aim of this study was to examine the neuronal circuitry
      underlying responses to script-driven imagery in traumatized police officers with
      and without PTSD and with low comorbidity rates. METHODS: In a case-matched
      control study, 30 traumatized police officers with and without PTSD underwent
      clinical assessment and (99m)technetium-hexa-methyl-propylene-amine-oxime single
      photon emission computed tomography scanning with neutral and trauma scripts.
      Statistical parametric mapping was applied to analyze changes in regional
      cerebral blood flow. RESULTS: The main findings were significantly less
      activation in the medial frontal gyrus and more activation in the right cuneus in
      the PTSD group relative to the trauma-exposed control group in reaction to trauma
      versus neutral scripts. Within the PTSD group, subjects showed less activation in
      the superior temporal gyrus, left lentiform nucleus, left middle frontal gyrus,
      and left inferior frontal gyrus in reaction to trauma scripts. CONCLUSIONS: We
      confirmed previous findings of dysfunction of the medial frontal gyrus in PTSD in
      a new population with low comorbidity rates. Other alterations were found in
      certain brain structures involved in emotional, memory, linguistic, visuospatial,
      and motor processing.

PMID- 15576063
TI  - The effect of successful treatment on the emotional and physiological response to
      carbon dioxide inhalation in patients with panic disorder.
AB  - BACKGROUND: A number of studies have shown that patients with panic disorder are
      more likely to have panic attacks during carbon dioxide inhalation than are
      normal comparison subjects. Some studies have shown that antipanic medications
      can reduce the anxiogenic response to carbon dioxide, but none have shown if this
      is the case for cognitive behavioral therapy or if successful treatment reduces
      the respiratory physiologic response to carbon dioxide. METHODS: Twenty-five
      patients with panic disorder and 13 normal comparison subjects underwent baseline
      testing with 5% and 7% carbon dioxide inhalation. The patients were then retested
      after at least 12 weeks of treatment with either antipanic medication or
      cognitive behavioral therapy. Comparison subjects were retested after a similar
      interval. RESULTS: Successful treatment resulted in lower panic rates, and
      reduced anxiogenic response. Treatment had no effect, however, on the respiratory
      physiologic response. CONCLUSIONS: There is dissociation in treatment response
      between the subjective and objective responses to carbon dioxide inhalation in
      panic disorder patients, with the former but not the latter showing positive
      change. We hypothesize that the strengthening of higher cortical control over
      subcortical fear-related structures, whether via medication or cognitive
      behavioral therapy treatment, results in less anxiety and fear in response to
      provoked symptoms reminiscent of naturally occurring panic.

PMID- 15576064
TI  - Valproate decreases inositol biosynthesis.
AB  - BACKGROUND: Lithium and valproate (VPA) are used for treating bipolar disorder.
      The mechanism of mood stabilization has not been elucidated, but the role of
      inositol has gained substantial support. Lithium inhibition of inositol
      monophosphatase, an enzyme required for inositol recycling and de novo synthesis,
      suggested the hypothesis that lithium depletes brain inositol and attenuates
      phosphoinositide signaling. Valproate also depletes inositol in yeast,
      Dictyostelium, and rat neurons. This raised the possibility that the effect is
      the result of myo-inositol-1-phosphate (MIP) synthase inhibition. METHODS:
      Inositol was measured by gas chromatography. Human prefrontal cortex MIP synthase
      activity was assayed in crude homogenate. INO1 was assessed by Northern blotting.
      Growth cones morphology was evaluated in cultured rat neurons. RESULTS: We found
      a 20% in vivo reduction of inositol in mouse frontal cortex after acute VPA
      administration. As hypothesized, inositol reduction resulted from decreased MIP
      synthase activity: .21-.28 mmol/LVPA reduced the activity by 50%. Among
      psychotropic drugs, the effect is specific to VPA. Accordingly, only VPA
      upregulates the yeast INO1 gene coding for MIP synthase. The VPA derivative N
      methyl-2,2,3,3,-tetramethyl-cyclopropane carboxamide reduces MIP synthase
      activity and has an affect similar to that of VPA on rat neurons, whereas another
      VPA derivative, valpromide, poorly affects the activity and has no affect on
      neurons. CONCLUSIONS: The rate-limiting step of inositol biosynthesis, catalyzed
      by MIP synthase, is inhibited by VPA; inositol depletion is a first event shown
      to be common to lithium and VPA.

PMID- 15576065
TI  - Anxious and depressive disorders and their comorbidity: effect on central nervous
      system noradrenergic function.
AB  - BACKGROUND: Although comorbidity of anxiety with depression is common,
      investigations of physiologic abnormalities related specifically to comorbidity
      are rare. This study examined relationships of DSM-IV-defined depression,
      anxiety, and their comorbidity to noradrenergic function measured by blunting of
      the growth hormone (GH) response to the alpha2 adrenoreceptor agonist (and
      imidazoline receptor agent) clonidine and by blood pressure and symptom
      responses. METHODS: Fifteen subjects with pure social anxiety or panic disorder,
      15 with pure major depression, and 18 with both depression and anxiety were
      compared with healthy control subjects matched for age and gender. Other factors
      known to affect GH (weight, menstrual status, prior antidepressant, or other drug
      exposure) were controlled. RESULTS: Anxiety produced GH blunting, but depression
      was associated with normal GH responses. The comorbid state did not affect
      results beyond the impact of anxiety. Preclonidine stress-related GH elevations
      were observed, to the greatest degree in anxious subjects. Relevant symptom, but
      not blood pressure, changes were significantly associated with blunting.
      CONCLUSIONS: With use of pure depression and anxiety groups and careful control
      of other factors known to affect GH, these results demonstrate central nervous
      system noradrenergic dysfunction in anxiety disorders. In contrast to less
      rigorously controlled studies, noradrenergic function in depression was normal.

PMID- 15576066
TI  - Family study of fibromyalgia and affective spectrum disorder.
AB  - BACKGROUND: Fibromyalgia is one member of a proposed group of psychiatric and
      medical disorders, collectively termed affective spectrum disorder (ASD),
      hypothesized to share possibly heritable pathophysiologic features. Two
      predictions of the ASD hypothesis were tested: ASD, taken as a single entity,
      aggregates in families; and fibromyalgia coaggregates with other forms of ASD in
      families. METHODS: Probands with and without fibromyalgia, together with their
      first-degree relatives, were administered structured diagnostic interviews.
      Noninterviewed relatives were diagnosed according to information provided by
      interviewed relatives. Aggregation and coaggregation of disorders were analyzed
      with proband predictive logistic and linear regression models. RESULTS: In 533
      relatives of 78 probands with fibromyalgia and 272 relatives of 40 probands
      without fibromyalgia, the estimated odds ratio (OR) (95% confidence interval) for
      the familial aggregation of ASD was 1.8 (.97, 3.2), p = .065, and the increase in
      number of forms of ASD in a relative for each additional form of ASD in a proband
      was .076 (.027, .1240), p = .002. The OR for the coaggregation of fibromyalgia
      with other forms of ASD was 2.0 (1.2, 3.2), p = .004; this remained significant
      even after excluding all mood-disorder diagnoses: 1.8 (1.1, 3.0), p = .012.
      CONCLUSIONS: These findings support familial aggregation of ASD collectively and
      familial coaggregation of fibromyalgia with other forms of ASD.

PMID- 15576067
TI  - Autism and head circumference in the first year of life.
AB  - BACKGROUND: It has been reported that children with autism and pervasive
      developmental disorder have a significantly smaller head circumference at birth
      and that their head circumference then increases disproportionately rapidly in
      the first year of life. METHODS: We attempted to replicate these findings using
      15 narrowly defined autistic children from the National Collaborative Perinatal
      Project and approximately 40,000 nonautistic control subjects. RESULTS: The
      autistic group had a slightly but not significantly larger head circumference at
      birth. At 4 months, the head circumference in the autistic group was not
      significantly larger than that of control subjects, but body weight and length
      were significantly larger in the autistic group. CONCLUSIONS: We believe this is
      the first report of significant general body growth in autistic children in
      infancy; the larger head circumference may be part of this excessive general
      growth.

PMID- 15576068
TI  - Omega-3 status and cerebrospinal fluid corticotrophin releasing hormone in
      perpetrators of domestic violence.
AB  - BACKGROUND: Elevated levels of corticotrophin-releasing hormone in the cortical
      hippocampal-amygdala pathway increase fear and anxiety, which are components of
      defensive and violent behaviors. Prostaglandins E2 and F2alpha, which increase
      corticotrophin-releasing hormone RNA expression in this pathway, are reduced by
      dietary intakes of omega-3 fats. METHODS: Among 21 perpetrators of domestic
      violence, cerebrospinal fluid and plasma were assessed for corticotrophin
      releasing hormone and fatty acid compositions, respectively. RESULTS: Lower
      plasma docosahexaenoic acid (wt% fatty acids) alone predicted greater
      cerebrospinal fluid corticotrophin-releasing hormone (pg/mL), in exponential (r =
      -.67, p < .006) and linear regressions (r = -0.68, p < .003 excluding four
      subjects with the highest docosahexaenate levels). CONCLUSIONS: In this small
      observational study, low plasma docosahexaenoic acid levels were correlated to
      higher cerebrospinal fluid corticotrophin-releasing hormone levels. Placebo
      controlled trials can determine if dietary omega-3 fatty acids can reduce
      excessive corticotrophin-releasing hormone levels in psychiatric illnesses.

PMID- 15576069
TI  - Metyrapone tests in patients with panic disorder.
AB  - BACKGROUND: Studies of hypothalamic secretion of corticotropin-releasing hormone
      (CRH) in patients with panic disorder in the nonpanic state (using CRH tests) are
      contradictory. No data about the hypothalamic-pituitary response to metyrapone
      are available. METHODS: Study participants included 14 patients with panic
      disorder (DSM-IV criteria) and 14 healthy control subjects who underwent a
      standard overnight metyrapone test and a combined metyrapone/low-dose
      dexamethasone test. RESULTS: Significant treatment effects of metyrapone and
      combined metyrapone/dexamethasone were found on plasma corticotropin, cortisol,
      and 11-deoxycortisol, but no differences between patients and control subjects
      emerged. Considering visual analogue scale ratings of anxiety, tension,
      restlessness, and Beck Depression Inventory scores as covariates, no group
      effects were detected. CONCLUSIONS: Standard overnight metyrapone tests do not
      support a hypersecretion of hypothalamic CRH in panic disorder. Furthermore, no
      evidence for increased glucocorticoid negative feedback in panic was found.
      Hypothalamic CRH secretion in the nonpanic state needs further research.

PMID- 15576070
TI  - Anxiety-like state associates with taste to produce conditioned taste aversion.
AB  - BACKGROUND: The interactions among experience, emotion, and memory are considered
      to be instrumental in the ontogeny and maintenance of acquired emotional and
      behavioral disorders (e.g., phobias). Here we address the question whether an
      anxiety-like state can associate with taste to produce conditioned taste aversion
      (CTA). METHODS: We have used an anxiogenic agent, the 5-HT2C receptor agonist
      meta-chlorophenylpiperazine (mCPP), to induce an anxiety-like emotional state in
      rats after consumption of an unfamiliar tastant. RESULTS: The anxiogenic agent
      induced CTA. The mCPP-induced CTA could be prevented by concomitant
      administration of ethanol, which is known to reverse mCPP-induced anxiety-like
      behavior, at a concentration that had no effect on CTA memory. In contrast,
      ethanol did not prevent LiCl-induced CTA. Administration of mCPP before the
      consumption of the tastant had no effect on the preference for that tastant.
      CONCLUSIONS: Taken together, these results indicate that anxiety-like state can
      serve as the unconditioned stimulus in CTA training. This finding may be relevant
      to the ontogeny of pathologies involving food aversion.

PMID- 15576072
TI  - Low efficacy electroconvulsive therapy in community settings.

PMID- 15576073
TI  - Demulsification by amphiphilic dendrimer copolymers.
AB  - Amphiphilic block copolymers with dendrimer structures were synthesized by anion
      polymerization and these dendritic macromolecules exhibited excellent
      demulsification performance for crude oil emulsion. According to the
      demulsification experiments, we determined that the copolymers became more
      efficient with more complex molecular structure due to increased penetrability.
      The physical model of demulsification intelligibly explained the micromechanism
      of flocculation and coalescence of water drops in emulsion because of the good
      adsorption and displacement behaviors of dendrimers.

PMID- 15576074
TI  - EDTA effect on the removal of Cu(II) onto TiO2.
AB  - The adsorption of Cu(II) and Cu(II)-EDTA onto TiO2 with variations in the pH,
      concentration, and molar ratio of Cu(II) to EDTA has been studied. The adsorption
      of Cu(II) and Cu(II)-EDTA onto TiO2 showed typical cationic- and anionic-type
      behavior, respectively. The removal of Cu(II) in an EDTA-excess system was less
      than that in an equimolar Cu(II)/EDTA system due to the competitive adsorption of
      EDTA and Cu(II)-EDTA onto the TiO2. The removal of Cu(II) was favorable at low pH
      for both the equimolar and EDTA-excess systems, while significant Cu(II) removal
      was observed over the entire pH range in a copper-excess system. For model
      predictions, the MINTEQA2 program employing an inner-sphere complexation and a
      diffuse layer model was used; the surface complexes used included Ti(OH2)OCu+,
      Ti(OH)EDTAH2-(2), and Ti(OH)EDTACu2-.

PMID- 15576075
TI  - Synthesis and characterization of iron oxide-coated silica and its effect on
      metal adsorption.
AB  - To accurately model metal mobility and bioavailability in soils and sediments,
      systematic adsorption studies are needed in considering heterogeneous, well
      characterized minerals. Two important surfaces are iron oxide and silica, which
      are ubiquitous and associated with one another in the environment playing
      important roles in metal distribution. This study focuses on the synthesis and
      characterization of such a system, iron oxide-coated silica. A three-level
      fractional factorial study was used to determine the optimum conditions for
      producing goethite-coated silica. The amount of coating achieved was between 0.59
      and 21.36 mg Fe g(-1) solid. The most significant factor in coating using either
      adsorption or precipitation was the particle size of silica, where Fe increased
      from an average of 0.85 to 9.6 mg Fe g(-1) solid as silica size decreased from
      1.5 to 0.2 mm. Other factors investigated, including coating temperature, initial
      iron concentration, and contact time, were of less importance. The iron oxide
      coatings were observed to be non-uniform, concentrated in rough concave areas.
      FTIR revealed a band shift as well as a new band indicating changes in the
      chemical environment of FeO and SiO bonds; these results along with abrasion
      studies suggest that the interaction between the oxide coating and silica surface
      potentially involves chemical forces. Because the nano-sized iron oxide coatings
      increased surface area, introduced small pores, and changed the surface charge
      distribution of silica, the coated system demonstrates a greater affinity for Ni
      compared to that of uncoated silica.

PMID- 15576076
TI  - Adsorption of Cu(II), Zn(II), Ni(II), Pb(II), and Cd(II) from aqueous solution on
      Amberlite IR-120 synthetic resin.
AB  - The adsorption of copper(II), zinc(II), nickel(II), lead(II), and cadmium(II) on
      Amberlite IR-120 synthetic sulfonated resin has been studied at different pH and
      temperatures by batch process. The effects of parameters such as amount of resin,
      resin contact time, pH, and temperature on the ion exchange separation have been
      investigated. For the determination of the adsorption behavior of the resin, the
      adsorption isotherms of metal ions have also been studied. The concentrations of
      metal ions have been measured by batch techniques and with AAS analysis.
      Adsorption analysis results obtained at various concentrations showed that the
      adsorption pattern on the resin followed Freundlich isotherms. Here we report the
      method that is applied for the sorption/separation of some toxic metals from
      their solutions.

PMID- 15576077
TI  - Morphology study of gold-chitosan nanocomposites.
AB  - Gold nanoparticles were prepared in the presence of chitosan via reduction of
      HAuCl4 with sodium borohydride. The gold-chitosan nanocomposite was formed by
      adsorbing chitosan molecules onto the gold nanoparticle surfaces. The resulting
      gold nanoparticles were characterized by transmission electron microscopy and UV
      vis spectroscopy. Morphology of gold-chitosan nanocomposite films was
      investigated by polarized optical microscopy. The morphology of chitosan crystal
      cast from the prepared nanocomposite was much different from that cast from
      chitosan solution due to the possible nucleation of gold nanoparticles. A
      branched-like structure or a cross-linked needle-like structure could be formed
      in nanocomposite films with different casting volumes.

PMID- 15576078
TI  - The influence of chitosans with defined degrees of acetylation on the
      thermodynamic data for copper coordination.
AB  - The interaction of copper with three different chitosans having degrees of
      deacetylation of 77.5, 81.5, and 86.1%, named C, A, and F, respectively, was
      followed by the batch method at 298+/-1 K and the values obtained were fitted to
      a modified Langmuir equation. These interactions were also obtained by
      calorimetric titration. Experimentally, 50.0 mg of each chitosan was suspended in
      doubly distilled water at 298.15+/-0.02 K under mechanical turbine stirring. The
      titration was performed by adding increments of 10 microl of a 0.10 mol dm3
      Cu(NO3)2 aqueous solution and the calorimetric isotherms obtained were adjusted
      to a modified Langmuir equation. From the net thermal effects K and DeltaH values
      were calculated, also permitting the acquisition of other thermodynamic data for
      the chitosan-copper interaction at the solid/liquid interface. The exothermic
      enthalpic values of -45.65+/-1.97, -49.91+/-1.57, and -48.64+/-0.82 kJ mol(-1),
      for chitosans C, A, and F, respectively, reflect the degree of deacetylation. The
      spontaneity of the systems is shown by the negative DeltaG values, -36.1+/-0.2,
      36.8+/-0.1, and -38.1+/-0.3 kJ mol(-1) for the same sequence of chitosans. The
      negative entropic values, -34, -44, and -35 J mol(-1) K(-1), are in agreement
      with an ordering of solvent as the complexation occurred. The intensity of the
      thermal effects and the thermodynamic data obtained from the copper/chitosan
      interactions can be associated with the ability of these biopolymers to extract
      copper from aqueous solutions.

PMID- 15576079
TI  - Ellipsometric study of nonionic polymer solutions.
AB  - The thickness and refractive index of adsorption films of poly(vinylpyrrolidone)
      (PVP) and poly(ethylene glycol) (PEG) were determined by null-ellipsometry at the
      air-aqueous solution interface. Both parameters, in the same way as the earlier
      studied dynamic surface elasticity and surface tension, exhibit rather abrupt
      changes when the concentration approaches the range of semidilute solutions. This
      behavior can be explained by the worsening of the solvent quality with increasing
      PEG concentration and by the PVP displacement from the surface by a contamination
      of high surface activity.

PMID- 15576080
TI  - Method of measuring charge distribution of nanosized aerosols.
AB  - In this paper, we present the development of a method to accurately measure the
      positive and negative charge distribution of nanosized aerosols using a tandem
      differential mobility analyzer (TDMA) system. From the series of TDMA
      measurements, the charge fraction of nanosized aerosol particles was obtained as
      a function of equivalent mobility particle diameter ranging from 50 to 200 nm.
      The capability of this new approach was implemented by sampling from a laminar
      diffusion flame which provides a source of highly charged particles due to
      naturally occurring flame ionization process. The results from the TDMA
      measurement provide the charge distribution of nanosized aerosols which we found
      to be in reasonable agreement with Boltzmann equilibrium charge distribution
      theory and a theory based upon charge population balance equation (PBE) combined
      with Fuchs theory (N.A. Fuchs, Geofis. Pura Appl. 56 (1963) 185). The
      theoretically estimated charge distribution of aerosol particles based on the PBE
      provides insight into the charging processes of nanosized aerosols surrounded by
      bipolar ions and electrons, and agree well with the TDMA results.

PMID- 15576081
TI  - Aggregation of paramagnetic particles in the presence of a hydrodynamic shear.
AB  - We present an experimental study of the aggregation of paramagnetic particles, in
      the presence of controlled laminar shear flow, conducted in microchannels
      subjected to an external magnetic field. The microfluidic channels are made of
      either glass/silicon or polydimethylsiloxane. In ranges of time up to hundreds of
      seconds, the growth mechanism of the linear chain consists of the accumulation of
      isolated particles or small clusters onto existing chains, which are all moving
      at different speeds. In this time regime the chain length increases linearly and
      has a growth rate that increases as a power law with the shear. At longer times
      the chain lengths saturate. The Smoluchovski model, which assumes single particle
      chain interactions only, closely reproduces the observations both qualitatively
      and quantitatively. In particular, the evolution of the growth rate of the mean
      chain length with respect to the shear rate S, predicted as S1/4, is found to be
      consistent with the experiments.

PMID- 15576082
TI  - Low-Knudsen-number photophoresis of aerosol spheroids.
AB  - The photophoretic motion of a freely suspended aerosol spheroid exposed to a
      radiative heat flux that is oriented arbitrarily with respect to its axis of
      revolution is analytically studied. The Knudsen number is assumed to be so small
      that the fluid flow can be described by a continuum model with a thermal slip at
      the particle surface. In the limit of small Peclet and Reynolds numbers, the
      appropriate energy and momentum equations are solved using the bifocal-coordinate
      transformations. Expressions for the photophoretic velocity and force are
      obtained in closed form for various cases of prolate and oblate spheroidal
      particles. The average photophoretic velocity and force for an ensemble of
      identical, noninteracting spheroids with random orientation distribution are also
      determined. The results indicate that the aspect ratio and relative thermal
      conductivity of a spheroidal particle and its orientation with respect to the
      incident light can have significant effects on its photophoretic behavior.

PMID- 15576083
TI  - Characterization of an effective cleaning procedure for aluminum alloys: surface
      enhanced Raman spectroscopy and zeta potential analysis.
AB  - We have developed a cleaning procedure for aluminum alloys for effective
      minimization of surface-adsorbed sub-micrometer particles and nonvolatile
      residue. The procedure consists of a phosphoric acid etch followed by an alkaline
      detergent wash. To better understand the mechanism whereby this procedure reduces
      surface contaminants, we characterized the aluminum surface as a function of
      cleaning step using surface enhanced Raman spectroscopy (SERS). SERS indicates
      that phosphoric acid etching re-establishes a surface oxide of different
      characteristics, including deposition of phosphate and increased hydration, while
      the subsequent alkaline detergent wash appears to remove the phosphate and modify
      the new surface oxide, possibly leading to a more compact surface oxide. We also
      studied the zeta potential of <5 microm pure aluminum and aluminum alloy 6061-T6
      particles to determine how surface electrostatics may be affected during the
      cleaning process. The particles show a decrease in the magnitude of their zeta
      potential in the presence of detergent, and this effect is most pronounced for
      particles that have been etched with phosphoric acid.

PMID- 15576084
TI  - Photocatalytic degradation of methylene blue by a combination of TiO2 and
      activated carbon fibers.
AB  - Photocatalytic degradation of methylene blue (MB) in aqueous solution was
      investigated using TiO2 immobilized on activated carbon fibers (ACFs). The TiO2
      and ACF combination (TiO2/ACF) was prepared by using epoxy as the precursor of
      the link between TiO2 and ACFs, followed by calcination at 460 degrees C in a N2
      atmosphere. The TiO2/ACF composite prepared was easier to handle than the
      original TiO2 powder in suspension. More significantly, the TiO2/ACF composite
      can be used repeatedly without a decline in photodegradation ability. After six
      cycles, the amount of MB removal for the TiO2/ACF composite was still slightly
      higher than that for fresh P25 TiO2 in suspension. Through measurement of
      chemical oxygen demand in the solution and the concentration of ammonium
      generated during degradation of MB, it was confirmed that MB molecules are
      mineralized instead of adsorbed by ACFs.

PMID- 15576085
TI  - Anion-induced adsorption of thallium complex on silver electrodes.
AB  - The interfacial behavior of thallium ions on polycrystalline silver electrodes is
      analyzed using cyclic voltammetric and chronocoulometric and impedance studies.
      The specificity associated with bromide ions leading to the anion-induced
      adsorption of the thallium complex is pointed out and the stoichiometry of the
      thallium complex is deduced.

PMID- 15576086
TI  - A study of ignition of metal impregnated carbons: the influence of oxygen content
      in the activated carbon matrix.
AB  - A study of the reason for the early ignition of coconut-based impregnated carbon
      in comparison with the peat-based impregnated carbon was conducted. The surface
      features of carbons were evaluated using various physicochemical methods. The
      metal analysis of the initial carbon indicated that the content of potassium was
      higher in the coconut-based carbon. The surface functional group analysis
      revealed the presence of similar surface species; however, the peat-based carbon
      was more acidic in its chemical nature. Since the oxygen content was higher in
      the peat-based carbon, the early ignition of the coconut-based material was
      attributed to its higher affinity to chemisorb oxygen, which leads to exothermic
      effects. This conclusion was confirmed by performing oxidation of coconut-based
      carbon prior to impregnation. This process increased the ignition temperature for
      Cu/Cr impregnated coconut-based material from 186 to 289 degrees C and for the
      Cu/Zn/Mo impregnated carbon from 235 to 324 degrees C.

PMID- 15576087
TI  - Deformation and bursting of nonspherical polysiloxane microcapsules in a spinning
      drop apparatus.
AB  - We analyze the deformation and bursting process of nonspherical organosiloxane
      capsules in centrifugal fields. Measurements were performed in a commercial
      spinning-drop tensiometer at different values of tube rotation. A theoretical
      analysis of the mechanics of initially ellipsoidal elastic shells subjected to
      centrifugal forces is developed where the deformation of the capsule is predicted
      as a function of the initial geometry and membrane elastic properties. For
      different types of organosiloxane membranes the Poisson number varies between 0
      and 0.9. This phenomenon points to a considerable reduction of the membrane
      thickness at the onset of mechanical stress. Membrane-breaking processes always
      initiated at one of the pole ends of the capsules. Such rupture processes can be
      interpreted in terms of the derived theoretical model.

PMID- 15576088
TI  - Numerical simulation of the anisotropic elastic field generated by a misfit
      dislocations along a NiSi2/Si/(001)GaAs heterotwin interface.
AB  - The purpose of this work is the numerical resolution, in the case of anisotropic
      elasticity, of the problem of a misfit dislocation located between an infinite
      substrate and two-layer composite. This case is obtained where the period of a
      network of misfit dislocations is taken as much greater than the thickness of the
      two foils. As a result, in the vicinity of the dislocation, the limiting boundary
      conditions will be close to those of Volterra translation dislocation. The
      elastic fields of displacement and stress are calculated for various orientations
      of the burger's vector, by inversion of a 30 x 30 computed matrix. Before this
      calculation, we tested the precision of the results of the program by comparing
      the interfacial relative displacement obtained from it with the results of the
      analytical expression describing this same displacement. The composite
      NiSi2/Si/(001)GaAs the subject of several investigations, is treated as an
      example.

PMID- 15576089
TI  - A study on NO removal of activated carbon fibers with deposited silver
      nanoparticles.
AB  - In this study, activated carbon fibers (ACFs), onto which silver (Ag)
      nanoparticles have been introduced by an electroplating technique, were used to
      remove NO. Surface properties of the ACFs were determined by X-ray diffraction
      and scanning electron microscopy. N2 adsorption isotherms at 77 K were
      investigated by BET and t-plot methods to characterize the specific surface areas
      and pore volumes, and NO removal efficiency was confirmed by a gas
      chromatographic technique. As for the experimental results, Ag content on the
      ACFs increased with plating time. However, adsorption properties such as the BET
      specific surface area and the total pore volume were somewhat decreased in the
      presence of Ag nanoparticles. NO removal efficiency of all Ag-ACFs was higher
      than that of untreated ACFs and increased with Ag content. However, a decrease in
      the extent of NO removal was shown in the excessively plated ACFs, which might be
      associated with the blocking of the micropores in the carbon; therefore, an
      optimal Ag content needs to exist in the presence of initially well-developed
      micropores to lead to an increase in the efficient NO removal ability of the ACF.

PMID- 15576090
TI  - Oscillating drop/bubble tensiometry: effect of viscous forces on the measurement
      of interfacial tension.
AB  - The oscillating drop/bubble technique is increasingly popular for measuring the
      interfacial dilatational properties of surfactant/polymer-laden fluid/fluid
      interfaces. A caveat of this technique, however, is that viscous forces are
      important at higher oscillation frequencies or fluid viscosities; these can
      affect determination of the interfacial tension. Here, we experimentally quantify
      the effect of viscous forces on the interfacial-tension measurement by
      oscillating 100 and 200 cSt poly(dimethylsiloxane) (PDMS) droplets in water at
      small amplitudes and frequencies ranging between 0.01 and 1 Hz. Due to viscous
      forces, the measured interfacial tension oscillates sinusoidally with the same
      frequency as the oscillation of the drop volume. The tension oscillation precedes
      that of the drop volume, and the amplitude varies linearly with Capillary number,
      Ca=DeltamuomegaDeltaV/gammaa(2), where Deltamu=mu(D)-mu is the difference between
      the bulk Newtonian viscosities of the drop and surrounding continuous fluid,
      omega is the oscillation frequency of the drop, DeltaV is the amplitude of volume
      oscillation, gamma is the equilibrium interfacial tension between the PDMS drop
      and water, and a is the radius of the capillary. A simplified model of a freely
      suspended spherical oscillating-drop well explains these observations. Viscous
      forces distort the drop shape at Ca>0.002, although this criterion is apparatus
      dependent.

PMID- 15576091
TI  - Interfacial properties of acidified skim milk.
AB  - The purpose of this study is to investigate the tension properties and
      dilatational viscoelastic modulus of various skim milk proteins (whole milk, EDTA
      treated milk, beta-casein, and beta-lactoglobulin) at an oil/water interface at
      20 degrees C. Measurements are performed using a dynamic drop tensiometer for
      15,000 s. The aqueous bulk phase is a skim milk simulated ultrafiltrate
      containing 11 x 10(-3) g L(-1) milk protein. At pH 6.7, beta-casein appears as
      the best to decrease the interfacial tension, whereas beta-lactoglobulin leads to
      the highest interfacial viscoelastic modulus value. Whole milk was almost as
      surface-active as individual beta-casein in terms of the final (steady-state)
      lowering of the interfacial tension, but the rate of tension lowering was
      smaller. EDTA treatment improved the rate of tension lowering of whole milk. The
      acidification of milk, from previous measurements, would lead to the enhancement
      of surface activity. At t=15,000 s, the order of effectiveness is pH 4.3 > pH 5.3
      = pH 5.6 > pH 6.7 whole milk, suggesting that pH 4.3 whole milk is the best
      surface active. As compared to pH 6.7 whole milk, the use of pH 5.3 and pH 5.6
      milk as surface active would result in the use of milk containing more free beta
      casein born of pH-dissociated casein micelles.

PMID- 15576092
TI  - Effect of temperature on the surface phase behavior and micelle formation of a
      mixed system of nonionic/anionic surfactants.
AB  - The adsorption and micellar behavior of diethylene glycol mono-n-tetradecyl ether
      (C14E2), sodium 3,6,9,12-tetraoxaoctacosanoate (TOOCNa), and their mixture at a
      1:1 molar ratio have been studied by film balance, Brewster angle microscopy
      (BAM), and surface tensiometry at different temperatures. The monolayers of pure
      C14E2 and its mixture with TOOCNa show a first-order phase transition with a
      conspicuous cusp point in their respective adsorption isotherms. This is further
      confirmed by the observation of bright two-dimensional condensed phase domains
      visualized by BAM just after the appearance of the phase transition. It is
      interesting to note here that for C14E2, condensed domains are observed up to 19
      degrees C, while in the mixed system, they are observed up to 22 degrees C. To
      understand why in the mixed system the domains are observed at higher
      temperatures than for pure C14E2, we have measured the temperature dependency of
      the equilibrium surface tension at > or = cmc (gammacmc) values of both the pure
      and the mixed systems. The gammacmc values of pure C14E2 remain almost constant,
      while those of pure TOOCNa and its mixture with C14E2 decrease appreciably with
      increasing temperature. It is concluded that higher degree of dehydration of the
      ethylene oxide (EO) chain reduces the head-group size of TOOCNa, which outweighs
      the combined effect of the repulsive interactions between the head-groups and the
      thermal motion of the adsorbed molecules. Furthermore, C14E2 being inserted into
      the TOOCNa monolayer reduces the electrostatic repulsions between the charged
      heads, and consequently, the adsorbed monolayers attain closer molecular packing.
      As a result, the gammacmc values of both pure TOOCNa and its mixture with C14E2
      decrease with increasing temperature. This facilitates the formation of condensed
      domains in the mixed system at higher temperatures, whereas none of the
      individual members can show any indicative feature of phase transition under the
      same experimental conditions.

PMID- 15576093
TI  - Effects of interactions on the formation of mixed micelles of 1,2-diheptanoyl-sn
      glycero-3-phosphocholine with sodium dodecyl sulfate and dodecyltrimethylammonium
      bromide.
AB  - Mixed micelles of the phospholipid 1,2-diheptanoyl-sn-glycero-3-phosphocholine
      (DHPC) with sodium dodecyl sulfate (SDS) or dodecyltrimethylammonium bromide
      (DTAB) in aqueous solutions and the effects of interactions between the
      components were studied by fluorescence and NMR measurements. The regular
      solution theory (RST) was applied to analyze the experimental critical micelle
      concentration values determined from the fluorescence spectra of pyrene in the
      mixed micelles. Negative values for the interaction parameter (beta12) were
      obtained for both DHPC + SDS and DHPC + DTAB mixtures, with the value being more
      negative in the former case. The negative beta12 values for the two systems imply
      that the interaction between the phospholipid and the two ionic surfactants is
      attractive in nature, being more intense in the case of DHPC + SDS. The
      interaction parameter, beta12, varies with composition of the mixtures indicating
      changes in packing. The proton NMR shifts are quite different for the two systems
      and also vary with composition. An interpretation of these experimentally
      determined chemical shifts in terms of the degree of compactness attributed to
      electrostatic and steric interactions in the mixed micelle supports the
      conclusions derived from the fluorescence cmc experiments.

PMID- 15576094
TI  - Unusual micellar properties of multiheaded cationic surfactants in the presence
      of strong charge neutralizing salts.
AB  - The aggregation properties of single-chain surfactants bearing one (H1), two
      (H2), and three (H3) trimethylammonium head groups have been studied by small
      angle neutron scattering (SANS). Growth of aggregates was observed to decrease
      dramatically with an increase in the number of head groups in the surfactants.
      The micelles grow progressively smaller with every increase in the number of head
      groups of the surfactants. Aggregation number (N) continuously decreases and the
      fractional charge (alpha) gradually increases with the increase in the number of
      head groups. The semiminor axis (a) and semimajor axis (b=c) of the micelle
      decrease strongly with the increase in the number of head groups. In the case of
      H1, dramatic micellar growth is observed on addition of salts such as KBr and
      sodium salicylate, but this type of micellar growth is not observed in the cases
      of H2 and H3 when the above salts are added to their micellar solutions.
      Aggregation number and size of the micelles remain almost the same, even after
      addition of KBr at a concentration as high as 100 mM. This observation with
      multiheaded cationic surfactants is unusual. Clearly, the charge density at the
      head group level of surfactants markedly influences their micellar aggregation
      properties.

PMID- 15576095
TI  - Oil recovery performances of surfactant solutions by capillary imbibition.
AB  - Critical parameters playing a role in oil recovery by capillary imbibition of
      surfactant solutions were studied. Experiments conducted on sandstone and
      carbonate samples using different oil and surfactant types were evaluated for
      surfactant selection. In this evaluation interfacial tension (IFT), surfactant
      type, solubility characteristics of surfactants, rock type, initial water (pre
      wet rock), and surfactant concentration were considered. In addition to these, a
      new technique was adopted to facilitate the surfactant screening process. This
      technique is based on assigning inorganic and organic property values and
      plotting organic conception diagrams (OCD) for surfactants. OCD defines the
      property of a compound in terms of physical chemistry in such a way that the
      property that depends much on the van der Waals force is called "organic" and the
      one that depends much on electric affinity is called "inorganic." Correlations
      between the capillary imbibition recovery performance and the properties of
      surfactant and oil (organic value (OV), inorganic value (IV), and IFT of
      surfactant solutions, oil viscosity, and surfactant type) were obtained. These
      correlations are expected to be useful in selecting the proper surfactant for
      improved oil recovery as well as identifying the effects of surfactant properties
      on the capillary imbibition performance.

PMID- 15576096
TI  - Phase diagram studies in two-surfactant ternary systems employing positron
      annihilation spectroscopy.
AB  - Positron annihilation lifetime parameters in condensed media are sensitive to
      structural and conformational changes. This property has been exploited to study
      the phase diagrams of two ternary cationic surfactant systems. Positron lifetime
      measurements were performed in cetyltrimethylammonium bromide
      (CTAB)/water/hexanol and tetradecyltrimethylammonium bromide
      (TTAB)/water/pentanol systems having varying concentrations of hexanol and
      pentanol respectively. For both the systems, changes were observed in the
      positron lifetime parameters whenever a phase transformation occurred. The
      various phase boundaries demarcated by this technique agrees well with those
      obtained by other conventional techniques. Besides this, the present work
      suggests the existence of two kinds of lamellar structures referred to as DI and
      DII phases in both the systems, which were otherwise considered to be a single D
      phase by other conventional techniques. The existence of such lamellar structures
      has been demonstrated by a change in the trend of o-Ps lifetime when the system
      passes from one type of lamellar structure to the other type. The results of
      these investigations are presented.

PMID- 15576097
TI  - Evaluation of the use of capillary numbers for quantifying the removal of DNAPL
      trapped in a porous medium by surfactant and surfactant foam floods.
AB  - The capillary number is used to quantify the mobilization potential of organic
      phases trapped within porous media. The capillary number has been defined in
      three different forms, according to types of flow velocity and viscosity used in
      its definition. This study evaluated the suitability of the capillary number
      definitions representing surfactant and surfactant foam floods by constructing
      capillary number-TCE saturation relationships. The results implied that the
      capillary number should be correctly employed, according to scale and fluid flow
      behavior. This study suggests that the pore-scale capillary number should be used
      only for investigating the organic-phase mobilization at the pore scale because
      it is defined by the pore velocity and the dynamic viscosity. The Newtonian-fluid
      capillary number using the Darcy velocity and the dynamic viscosity may be
      suitable for quantifying flood systems representing Newtonian fluid behavior. For
      viscous-force modified flood systems such as surfactant-foam floods, the apparent
      capillary number definition employing macroscopic properties (permeability and
      potential gradient) may be used to appropriately represent the desaturation of
      organic phases from porous media.

PMID- 15576098
TI  - Effect of surfactant head group size on polyelectrolyte-surfactant interactions:
      steady-state and time-resolved fluorescence study.
AB  - Interactions between sodium poly(acrylate) (NaPAA) and
      dodecyltrimethyl/ethyl/propyl/butylammonium bromide (C12NM, C12NE, C12NP, and
      C12NB) were studied. Variation of the physicochemical properties of the
      surfactants and polyelectrolyte-surfactant mixtures, such as critical micelle
      concentration (cmc), critical aggregation concentration (cac), micellar
      micropolarity, aggregation number, and pyrene lifetime, were determined by steady
      state and time-resolved fluorescence methods. It is shown that the surfactant
      head group size has a striking effect on the interaction between surfactant and
      polyelectrolyte. The interaction is weakened gradually when the surfactant head
      group is increased from trimethyl to tripropyl, which might be owing to the
      increase of the steric hindrance between the polyelectrolyte chain and micellar
      surface. But when the head group is tributyl, the interaction is enhanced and
      stronger than that between C12NP and NaPAA. This might be explained by the self
      association of the C12NB head groups.

PMID- 15576099
TI  - A slender-body micromechanical model for viscoelasticity of magnetic colloids:
      comparison with preliminary experimental data.
AB  - The storage modulus, G', together with the yield stress, is an essential quantity
      characterizing the rheological properties of magnetic field-responsive
      suspensions (magnetorheological fluids or MRF). In this work, we present both
      experimental and theoretical results on the viscoelastic properties of MRFs. Two
      MRFs are used: In one the solid phase consists of cobalt ferrite particles +
      silica gel, with silicone oil as liquid phase. The second system is formed by
      carbonyl iron + silica gel also dispersed in silicone oil. The cobalt ferrite
      particles are synthesized as monodisperse colloidal spheres with an average
      diameter of 850 nm. We describe a new model based on the slender-body approach
      for hydrodynamic interactions. The predictions of the model are compared to
      preliminary experimental G' data obtained in a controlled stress plate-plate
      rheometer. It is found that the model gives the correct order of magnitude for
      the highest fields in iron suspensions, but underestimates the experimental
      results obtained in ferrite ones. In the case of high permeability materials such
      as carbonyl iron, by the inclusion of high-order multipolar interactions and
      saturation effects we also predict the order of magnitude of the experimental
      results. When dealing with low permeability cobalt ferrite based MRFs, other
      effects, such as remanence (at low fields) and saturation (at high fields), must
      be considered.

PMID- 15576100
TI  - Modeling of the linear viscoelastic properties of oil-in-water emulsions.
AB  - The aim of this work is to use a recently developed statistical model of
      dispersions with nonhydrodynamic interactions to describe the linear viscoelastic
      properties of emulsions of Newtonian liquids. None of the existing models can
      describe the rheological behavior of such systems, particularly the elastic
      properties, in the linear regime. We first present the results of numerical
      simulations of our model applied to emulsions. We show that taking
      nonhydrodynamic interactions into account allows to predict that emulsions of two
      purely viscous liquids have a complex viscoelastic behavior. We then compare the
      model to experimental results on oil/water emulsions, stabilized with ionic and
      nonionic surfactants. We find out that our statistical mechanical approach gives
      a much better description of the viscoelastic behavior of these samples than
      purely hydrodynamic models do. However, the elasticity observed is underestimated
      by our model. We indicate further theoretical developments which could improve
      the description of the viscoelastic properties of emulsions.

PMID- 15576101
TI  - Separation of charged colloids by a combination of pulsating lateral electric
      fields and poiseuille flow in a 2D channel.
AB  - Separation of colloidal particles of different sizes is becoming increasingly
      important due to rapid developments in the area of proteomics, genetic
      engineering, drug discovery, etc. In particular, there is a need to accomplish
      these separations on a microscale in 'lab-on-a-chip' devices. In this paper, we
      propose a new method for accomplishing separation of charged colloids of
      different sizes in a microchannel. This method involves a combination of pulses
      of lateral electric fields and Poiseuille flow in the axial direction. We develop
      a model for this separation technique and obtain closed form solutions for the
      mean velocity and the dispersion coefficient for a pulse of molecules introduced
      into the channel. These expressions are then utilized to determine the channel
      length and the separation time. For reasonable value of design constants, the
      proposed technique can separate molecules of different sizes that have
      diffusivities of 10(-10) and 0.5 x 10(-10) m2/s in 15.7 s in a 3.7 mm long
      channel. The length and the time increase to 5.45 cm and 231 s if the ratio of
      the diffusivities is reduced from 2 to 1.2, i.e., the latter diffusivity is
      increased to 0.835 x 10(-10) m2/s, while keeping all the other parameters the
      same. If the diffusivities are about 10(-9) m(2)/s, the length and the time for
      separation are 1 cm and 17.5 s for D1/D2=2, and 16 cm and 269 s for D1/D2=1.2.

PMID- 15576102
TI  - Electroviscoelasticity of liquid/liquid interfaces: fractional-order model.
AB  - A number of theories that describe the behavior of liquid-liquid interfaces have
      been developed and applied to various dispersed systems, e.g., Stokes, Reiner
      Rivelin, Ericksen, Einstein, Smoluchowski, and Kinch. A new theory of
      electroviscoelasticity describes the behavior of electrified liquid-liquid
      interfaces in fine dispersed systems and is based on a new constitutive model of
      liquids. According to this model liquid-liquid droplet or droplet-film structure
      (collective of particles) is considered as a macroscopic system with internal
      structure determined by the way the molecules (ions) are tuned (structured) into
      the primary components of a cluster configuration. How the tuning/structuring
      occurs depends on the physical fields involved, both potential (elastic forces)
      and nonpotential (resistance forces). All these microelements of the primary
      structure can be considered as electromechanical oscillators assembled into
      groups, so that excitation by an external physical field may cause oscillations
      at the resonant/characteristic frequency of the system itself (coupling at the
      characteristic frequency). Up to now, three possible mathematical formalisms have
      been discussed related to the theory of electroviscoelasticity. The first is the
      tension tensor model, where the normal and tangential forces are considered, only
      in mathematical formalism, regardless of their origin (mechanical and/or
      electrical). The second is the Van der Pol derivative model, presented by linear
      and nonlinear differential equations. Finally, the third model presents an effort
      to generalize the previous Van der Pol equation: the ordinary time derivative and
      integral are now replaced with the corresponding fractional-order time derivative
      and integral of order p<1.

PMID- 15576103
TI  - Electrophoretic mobility and primary electroviscous effect of dilute "hard"
      prolate ellipsoids.
AB  - Electrophoretic mobilities and primary electroviscous coefficients are determined
      for "hard" prolate ellipsoids of axial ratio less than or equal to 4 in KCl,
      NaCl, and Tris-glycine salt solutions. Account is taken of the steady state
      distortion of the ion atmosphere around the ellipsoid by numerical solution of
      the coupled Poisson, low-Reynolds-number Navier-Stokes, and ion transport
      equations. This is accomplished by a boundary element procedure. Results are
      presented as ratios of mobilities and primary electroviscous coefficients of
      ellipsoids to those of corresponding spheres. It is shown that the
      electrophoretic mobility of an ellipsoid is very similar to that of a sphere
      under similar conditions of size, ionic strength, salt type, and zeta potential.
      Other factors being equal, shape has little effect on electrophoretic mobility.
      For the primary electroviscous coefficient, on the other hand, there is a
      substantial shape effect. It is argued that the complementary techniques of
      electrophoresis and viscosity together provide an effective means of studying the
      size, charge, and shape of macroions and colloidal particles.

PMID- 15576104
TI  - Influence of fluorination on surface and dielectric characteristics of polyimide
      thin film.
AB  - In this study, the effects of fluorine treatment on surface properties, surface
      free energies, and dielectric constants of polyimide thin films were studied
      using X-ray photoelectron spectroscopy, contact angles, and dielectric
      characteristics, respectively. The glass transition temperature of fluorinated
      polyimide film gradually decreases with increasing fluorine pressure. The surface
      free energies and dielectric constants of the film decreased with increasing
      amount of the treatment fluorine gas. It was explained that the replacement of
      fluorine led to a decrease of the local electron polarization of polyimide and an
      increase of the free volume, which could be attributed to the relatively large
      volume of fluorine.

PMID- 15576105
TI  - Pattern formation through selective chemical transformation of self-assembled
      benzaldimine monolayer by soft X-ray irradiation.
AB  - Benzaldimine monolayer was exposed to soft X-rays, and the involved chemical
      transformation was investigated using X-ray photoelectron spectra and near-edge X
      ray absorption fine structure spectroscopy. The spectroscopy indicated that
      irradiation of soft X-ray (550 eV)-induced selective transformation of the imine
      group into a nonhydrolyzable one, i.e., the amine group. Utilizing the selective
      chemical transformation of the imine group with the soft X-ray irradiation, we
      were able to generate a micropattern. AFM images showed that the patterning with
      alternating surface topology was effective. The patterned monolayer was further
      modified with biotin and Cy3-tagged Streptavidin sequentially. Fluorescence
      images showed that the above molecules were selectively immobilized onto the
      amine-terminated region of the patterned surface. The current system is found to
      be more efficient than the predecessor, 4-nitrobenzaldimine monolayer.

PMID- 15576106
TI  - Abstracts from the 57th Annual Meeting of the Neurosurgical Society of America.

PMID- 15576110
TI  - Clinical outcomes following cervical laminoplasty for 204 patients with cervical
      spondylotic myelopathy.
AB  - BACKGROUND: Laminoplasty is a well-recognized technique for decompressing the
      cervical spine in cases of spondylotic myelopathy and ossification of the
      posterior longitudinal ligament. This technique, originally popularized in Asia,
      is becoming more widespread, but to date there have been few reports of clinical
      series from North American centers. METHODS: Retrospectively we reviewed (1986
      2001) 204 cases of open door laminoplasty. All patients presented with symptoms
      and magnetic resonance imaging (MRI) findings consistent with myelopathy
      secondary to multisegmental cervical stenosis with spondylosis and underwent
      decompression from C3 to C7. Improvement in myelopathy was assessed with the
      Nurick Score. RESULTS: Average age was 63 years (range 36 to 92). Follow-up
      averaged 16 months. Postoperatively, Nurick scores improved by 1 point in 78
      patients, 2 points in 37 patients, 3 points in 7 patients, and 4 points in 5
      patients; 74 patients experienced no improvement, and 3 patients deteriorated by
      one point. There was no statistical difference in myelopathy outcomes when
      comparing patients older and younger than 75 years of age. In two patients there
      was radiographic progression of kyphosis, but in no case was subsequent fusion
      required. Six patients without neck pain preoperatively developed new intractable
      neck pain after surgery. CONCLUSIONS: Open door expansile laminoplasty is a safe
      and effective method for treating cervical spondolytic myelopathy. Laminoplasty
      is thus an alternative to anterior surgery that can be accomplished quickly with
      minimal blood loss, minimizing risks in elderly patients.

PMID- 15576113
TI  - Percutaneous vertebroplasty for treatment of thoracolumbar spine bursting
      fracture.
AB  - OBJECTIVE: Percutaneous vertebroplasty can be very beneficial for patients with
      vertebral osteoporotic compression fractures. To the best of our knowledge,
      however, there has been no mention in any literature regarding the use of
      percutaneous vertebroplasty for the treatment of spinal burst fracture. METHODS:
      A preliminary study was conducted on 6 patients with traumatic burst fractures of
      vertebrae treated with percutaneous vertebroplasty starting in June 2000.
      Fractures involving the anterior and middle columns of the vertebrae and the
      canal were mildly compressed by the retropulsed bone fragment. However, there was
      no obvious neurologic deficit in these patients. They initially underwent
      conservative treatment and thoracolumbar spinal orthosis (TLSO) brace for at
      least 3 months, but the intractable pain caused patients to be bedridden for
      prolonged periods of time and limited daily activity. As a result, the patients
      underwent percutaneous vertebroplasty with polymethylmethacrylate (PMMA) for
      treatment of spinal burst fractures. RESULTS: Six male patients (mean age: 38.2)
      who suffered from burst fractures of vertebrae with disabling back pain
      refractory to analgesic therapy and TLSO brace were treated in this study. The
      duration of conservation treatment period was 3.5 months to 8 months (mean: 5.2
      months). There was no motility. However, 4 vertebrae (66.7%), on radiographs
      revealed evidence of PMMA leakage through the endplate fracture site into either
      the disc space or the paravertebral space, without any evident clinical symptoms.
      No intracanal leakage was seen, and no patient needed a secondary surgical
      intervention. Pain decreased from 84.3 +/- 5.4 mm at baseline to 34.7 +/- 4.4 mm
      at the third postoperative day, 30.2 +/- 5.8 at 3 months and 24 +/- 3.5 mm at 12
      months. The reduction in pain from baseline to the 3-day and 3 month mark was
      statistically significant (p < 0.05). The mobility was at least 2 levels of
      improvement (mean improvement 2.7 points) at 12-months postoperative. CONCLUSION:
      In highly selective patients, percutaneous vertebroplasty can be an alternative
      method for the treatment of spinal burst fractures and the prevention of
      complications from major surgical procedures. However, this procedure still has
      potential risks and should be employed with extreme caution to prevent
      extravasation of PMMA into the spinal canal.

PMID- 15576115
TI  - Percutaneous CT-guided chemical thoracic sympathectomy for patients with palmar
      hyperhidrosis after transthoracic endoscopic sympathectomy.
AB  - BACKGROUND: Palmar hyperhidrosis is a common functional disorder in the Asians.
      Currently, transthoracic endoscopic sympathectomy (TES) is considered to be the
      treatment of choice for this entity because of its high initial success rate and
      minimal morbidity. However, primary failure and recurrence of hyperhidrosis
      occurred in some patients, even with a very low incidence. We present our
      experience in the treatment of primary failure and recurrence of hyperhidrosis
      after TES by means of percutaneous computer tomography (CT) guided ethanol
      thoracic sympathectomy. METHODS: From July 1999 to July 2001, 11 patients (2
      males and 9 females with a mean age of 25.9 years, range: 19-44 years) of this
      subgroup underwent percutaneous CT-guided chemical thoracic sympathectomy.
      Failure of the first sympathectomy was caused by severe pleural adhesion (from
      the previous operative findings) in 7 patients. The remaining 4 patients were
      recurrent palmar hyperhidrosis. All patients underwent unilateral procedures (3
      on the right and 8 on the left). RESULTS: All patients were followed for at least
      2 years after the treatment. Needle puncture was possible without difficulty in
      all patients. All patients had satisfactory results with minimal complication. No
      recurrence was noted at follow-up. CONCLUSION: In summary, percutaneous CT-guided
      ethanol thoracic sympathectomy could be an easy, safe, and alternative strategy
      to treat patients with palmar hyperhidrosis after failure or recurrence after
      TES.

PMID- 15576117
TI  - Multiple myeloma-associated solitary epidural amyloidoma of C2-C3 without bony
      connection or myelopathy: case report and review of the literature.
AB  - BACKGROUND: A large solitary amyloidoma in the cervical epidural space without
      bony connection and with minimal spinal cord compression and no myelopathy, as a
      first manifestation of disseminated amyloidosis in a multiple myeloma patient,
      has not been reported previously; this case is thereby distinct from the seven
      prior reports in the world literature, of a solitary amyloidoma of the cervical
      spine. CASE DESCRIPTION: A 72-year-old male, recently diagnosed with multiple
      myeloma, presented with a neuropathy that prompted a screening MRI of the
      cervical spine. This disclosed a large mass in the upper cervical epidural area
      felt to pose a high morbidity/mortality risk, leading to successful surgical
      removal of the amyloidoma mass. This then led to further testing that showed
      previously unsuspected widespread amyloidosis, which was subclinical up to that
      time. CONCLUSIONS: In patients with a newly discovered amyloidoma, whether or not
      in the setting of known multiple myeloma, further evaluation should be done to
      detect the presence of amyloidosis. If the mass is discovered de novo, then an
      investigation should be carried out to determine if multiple myeloma, as well as
      amyloidosis, is present.

PMID- 15576119
TI  - Prospective study on cranioplasty with individual carbon fiber reinforced polymer
      (CFRP) implants produced by means of stereolithography.
AB  - BACKGROUND: The aim of this study was to evaluate the value of carbon fiber
      reinforced polymer (CFRP) cranial implants produced by means of 3-dimensional
      (3D) stereolithography (SL) and template modeling for reconstructions of complex
      or extensive cranial defects. PATIENTS: A series of 41 cranioplasties with
      individual CFRP implants was performed in 37 patients between April 1996 and
      November 2002. Only patients with complex and/or large cranial defects were
      included, most of them having extended scarring or dural calcification and poor
      quality of the overlying soft-tissue cover after infection or multiple preceding
      operations. Involvement of frontal sinus, a known risk factor for complications
      after cranioplasty, was the case in 21 patients (51.2%). METHODS: A computer
      based 3D model of the skull with the bony defect was generated by means of
      stereolithography after acquisition, evaluation and transfer of the patient's
      helical computed tomography (CT) data. A wax template of the defect that was used
      to design the individual prosthesis-shape was invested in dental stone. Then, the
      cranial implant was fabricated out of CFRP by loosen mold. RESULTS:
      Reconstruction of defects measuring up to 17 x 9 cm was performed. The intra
      operative fit of the implants was excellent in 36 (87.8%), good in 1 (2.4%), and
      fair in 4 (9.8%) of the cases. Problems of implant fit occurred because of
      extended scarring and poor quality of soft-tissue cover. Adverse reactions were
      observed in 5 patients (1 subdural, 1 subcutaneous hematoma, 2 infections, 1
      allergic reaction). Excellent contours and a solid stable reconstruction have
      been maintained in 30 out of 35 remaining plates (mean follow-up 3.6 years). No
      adverse effects concerning postoperative imaging, the accuracy of
      electroencephalograms and radiation therapy have been observed. CONCLUSIONS: The
      authors believe that this relatively new technique represents an advance in the
      management of complex and large cranial defects, but seems less suitable for
      simple defects because of cost-intensive techniques. Because of the high
      mechanical strength, biocompatibility, innovative design, and especially
      radiolucency, CFRP implants should, however, be considered in smaller defects if
      further imaging investigations or irradiation therapies are necessary.

PMID- 15576120
TI  - Major venous sinus resection in the surgical treatment of recurrent aggressive
      dural based tumors.
AB  - BACKGROUND: Despite gross total resection, aggressive dural based tumors invading
      major venous sinuses have high recurrence rates with poor long-term
      survivability. Options for aggressive surgical management of dural sinus invasion
      may be limited by the inherently high risk of morbidity and mortality. METHODS:
      Between July 1996 and July 2002, 5 cases of recurrent aggressive dural based
      tumors were operated on. Gross total resection had been previously performed in 4
      cases, and near total resection in 1 case. Tumor pathology included 2 malignant
      meningiomas, 1 hemangiopericytoma, 1 atypical meningioma, and 1 benign meningioma
      with atypical features. All tumors recurred within 3 to 47 months and occluded a
      major venous sinus (four superior sagittal and one dominant right transverse
      sinus). Gross total resection of tumor and involved venous sinus was accomplished
      in each case. RESULTS: Three patients had no signs of clinical or radiographic
      recurrence at 10, 18, and 53 months of follow up. One patient who developed a
      fatal pulmonary embolism 10 months postoperatively had evidence of tumor
      progression on autopsy. One patient had tumor recurrence at 10 months, but is
      alive at 38 months and receiving adjunctive therapy. CONCLUSION: For aggressive
      dural based tumors that recur with invasion of a major venous sinus, radical
      resection of tumor and occluded sinus can be performed safely and may improve
      long-term survival.

PMID- 15576122
TI  - Management of poor-grade patients with aneurysmal subarachnoid hemorrhage in the
      acute stage: Importance of close monitoring for neurological grade changes.
AB  - BACKGROUND: The optimal management of poor-grade patients with aneurysmal
      subarachnoid hemorrhage (SAH) remains controversial. We evaluated therapeutic
      outcomes to identify appropriate treatments for SAH patients admitted with a poor
      grade. METHODS: We retrospectively studied 136 patients admitted within 6 hours
      after SAH onset with a poor Hunt & Kosnik Grade (IV and V). RESULTS: Of 136 poor
      grade patients, 20 with massive intracerebral or subdural hematoma underwent
      urgent hematoma evacuation and aneurysmal neck clipping. Seven of these achieved
      a favorable outcome (good recovery or moderate disability). Another 7 patients
      with prominent hydrocephalus or massive intraventricular hematoma underwent
      urgent continuous ventricular drainage. Of these, 4 manifested spontaneous grade
      improvement and underwent neck clipping; the other 3 died resulting from
      rebleeding. The remaining 109 patients whose poor grade was primarily because of
      SAH were observed without immediate surgery. In 43 patients of 109, the grade
      improved within 24 hours after hospitalization and within 38 hours in the other 4
      patients. Aneurysmal neck clipping was performed in these 47 patients and a
      favorable outcome was achieved in 25 patients. The remaining 62 patients did not
      improve and the outcome was unfavorable. CONCLUSIONS: Poor-grade SAH patients
      should be treated according to the pathogenesis underlying their poor grade.
      Close monitoring for a grade change over the first 24 hours after hospitalization
      is mandatory in patients whose poor grade is primarily because of the SAH and
      helps to determine the appropriateness of surgery.

PMID- 15576125
TI  - Management of unruptured cerebral aneurysms in patients with polycystic kidney
      disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (PKD) is a hereditary
      disorder characterized by bilateral multiple renal cysts and early onset chronic
      renal failure. PKD patients tend to suffer their subarachnoid hemorrhage at a
      younger age. Unruptured aneurysms in PKD patients are not always innocuous, and
      proactive treatment has been indicated for these lesions. However, the management
      of PKD patients undergoing unruptured cerebral aneurysm surgery has been
      documented on only a few occasions. The purpose of this study was to better
      define the management of unruptured cerebral aneurysms in patients with PKD.
      METHODS: We present a retrospective review of the management of unruptured
      cerebral aneurysms in 16 patients with PKD. Eight patients were maintained
      through chronic hemodialysis whereas the remaining 8 patients did not require
      hemodialysis, at the time of treatment of their cerebral aneurysms. The mean
      follow-up period was 24 months. RESULTS: In the nonhemodialysis patients
      prophylactic hemodialysis was routinely performed after cerebral angiography to
      prevent deterioration of the pre-existing renal dysfunction. Microsurgical
      clipping of the aneurysm was performed in 15 patients (7 nonhemodialysis and 8
      hemodialysis patients) and intravascular coil embolization was performed in 1
      nonhemodialysis patient. One nonhemodialysis patient who underwent microsurgical
      clipping required a temporary hemodialysis after surgery, but the patient was not
      shifted to chronic hemodialysis. No patients developed postprocedural
      complications, and each showed an excellent recovery. CONCLUSION: PKD patients
      with unruptured cerebral aneurysms can be safely treated with an appropriate
      treatment strategy including the use of prophylactic hemodialysis.

PMID- 15576127
TI  - Persistent primitive hypoglossal artery associated with proximal posterior
      inferior cerebellar artery aneurysm.
AB  - BACKGROUND: A persistent primitive hypoglossal artery (PPHA) is a rare anomaly.
      The association of PPHA with intracranial aneurysms of the artery has also been
      rarely reported. We surgically treated a case of PPHA associated with a ruptured
      saccular aneurysm at the proximal posterior inferior cerebellar artery (PICA).
      CASE DESCRIPTION: The patient was admitted because of subarachnoid hemorrhaging.
      Angiography and three-dimensional computed tomography (CT) angiography (3D-CTA)
      demonstrated a left PPHA entering the posterior fossa through the left large
      hypoglossal canal. The left vertebral artery was absent. A saccular aneurysm was
      found at the junction of the PPHA and the proximal PICA. 3D-CTA showed not only
      the aneurysm itself but also the anatomical relationship between the aneurysm and
      the surrounding structures. Therefore, 3D-CTA was very useful in planning the
      surgery. The neck of the aneurysm was clipped through a far lateral approach
      associated with a C1 laminectomy, because this case had a large posterior
      condylar emissary vein and the aneurysm was located just posteroinferior to the
      hypoglossal canal. CONCLUSIONS: A case of PPHA associated with an aneurysm at the
      proximal PICA is reported. This case not only had a large hypoglossal canal but
      also had a huge posterior condylar emissary vein in the large posterior condylar
      canal. Anomalous structures associated with PPHA are also discussed. Finally, 3D
      CTA proved to be very useful in planning the optimal surgical modality around the
      lateral portion of the foramen magnum.

PMID- 15576129
TI  - Surgical treatment of a syringomyelia associated with an idiopathic arachnoid
      malformation disclosed by preoperative MRI.
AB  - BACKGROUND: We describe the very rare condition of an idiopathic spinal arachnoid
      malformation associated with syringomyelia (SM) and depicted on preoperative
      magnetic resonance imaging (MRI) whose features were confirmed at surgery. CASE
      DESCRIPTION: A 34-year-old female suffered from progressive gait impairment
      because of lower limb palsy and sensory disturbances. MRI demonstrated a bulging
      membrane at the T6 level that was transversely stretched between the dorsal
      aspect of the spinal cord and the posterior dura mater. At this level, the spinal
      cord appeared atrophic and pushed anteriorly against the dura with enlargement of
      the posterior subarachnoid spaces (SAS) and focal collapse of an associated
      panmedullar SM. Surgery consisted in releasing the arachnoid malformation and
      opening the inferior segment of the syringomyelic cavity. Pathological
      examination revealed a fibro-sclerotic tissue with cellular areas of meningo
      endothelial cells. Postoperative neurological status progressively improved but
      slightly. Three-months and 1 year postoperatively, MRI showed the collapse of the
      whole SM and restoration of cerebrospinal fluid (CSF) flow at the treated T6
      level. CONCLUSION: Spinal arachnoid malformations associated with SM are very
      rare and have never been described up to now on MRI. Surgical removal of the
      causative malformation allows spinal cord decompression and prevents the
      recurrence of the SM by restoring normal CSF circulation.

PMID- 15576133
TI  - Re: Yi HJ, Oh SH, Hong HJ, Lee KS. Common peroneal nerve palsy as a complication
      of anterior cervical operation: A case report. Surg Neurol 2004;61:379-83.

PMID- 15576134
TI  - The mechanism of corrosion of palladium-silver binary alloys in artificial
      saliva.
AB  - Palladium dental casting alloys are alternatives to gold alloys. The aim of this
      study was to determine the electrochemical behaviour and the corrosion mechanism
      of binary silver-palladium alloys. Seven binary silver-palladium alloys and pure
      palladium and silver were tested in a model saliva solution. Electrochemical
      tests included corrosion potential, polarization resistance, and potentiodynamic
      polarization measurements. The corrosion products, which may be theoretically
      formed, were determined by thermodynamic calculation. The behaviour of silver and
      silver-rich alloys was dominated by the preferential formation of a thiocyanate
      surface layer, which controlled the free corrosion potential. Palladium dissolved
      in the form of a thiocyanate complex, but the surface became passivated by either
      palladium oxide or solid palladium thiocyanate layer, the thermodynamic
      calculations indicating preference for the oxide. Palladium-rich alloys showed
      evidence of silver depletion of the surface, resulting in behaviour similar to
      palladium. Examination of binary silver-palladium alloys has made possible
      determination of the role of the components of the alloys and model saliva in the
      corrosion behaviour. The findings are applicable to the more complex commercial
      dental alloys containing silver and palladium as major components.

PMID- 15576135
TI  - Constitutive modeling of the densification and the grain growth of hydroxyapatite
      ceramics.
AB  - In the present work, constitutive models for densification and grain growth were
      employed to investigate the sintering behavior of pure hydroxyapatite ceramics.
      For densification study, lattice diffusion, grain-boundary diffusion, and
      interface reaction mechanisms, and for grain-growth study, surface diffusion
      mechanism, were considered respectively. Hydroxyapatite ceramics were
      pressurelessly sintered. The sintering results were discussed and compared with
      the modeling results. Based on the constitutive models employed and the
      experimental results obtained, grain-boundary diffusion was identified as the
      dominant mechanism for the densification of the investigated hydroxyapatite. The
      grain-growth model provided a good prediction to the grain growth of the
      investigated hydroxyapatite. The activation energies for densification and grain
      growth of hydroxyapatite ceramics were evaluated as 1150+/-40 and 1020+/-40 KJ
      mol(-1), respectively.

PMID- 15576136
TI  - A composite coating by electrolysis-induced collagen self-assembly and calcium
      phosphate mineralization.
AB  - A composite coating that is composed of collagen protein and calcium phosphate
      minerals is considered to be bioactive and may enhance bone growth and fixation
      of metallic orthopedic implants. In this study, we have successfully developed a
      uniform collagen fibril/octacalcium phosphate composite coating on silicon
      substrate by electrolytic deposition (ELD). The coating deposition was done
      through applying a constant potential to the cathode in a three-electrode
      electrochemistry cell that contain a mild acidic (pH 4.8-5.3) aqueous solution of
      collagen molecules, calcium and phosphate ions. The coating process involved self
      assembly of collagen fibrils and the deposition of calcium phosphate minerals as
      a result of cathode reaction and local pH increase. The two steps could be
      synchronized to form a bone-like composite at nanometer scale through proper
      adjustment of the solution and deposition parameters. Coating morphology, crystal
      structure and compositions were analyzed by optical and fluorescence microscopy,
      scanning and transmission electron microscopy, energy dispersive X-ray analysis,
      inductively coupled argon plasma optical emission spectrophotometry, and Fourier
      transformed infrared spectroscopy. Under typical deposition conditions, the
      cathode (Si) surface formed a thin (100 nm) layer of calcium phosphate coating,
      on top of which a thick (approximately 100 microm) composite layer formed. The
      porous composite layer consists of a collagen fibril network on which clusters of
      octacalcium phosphate crystals nucleate and grow. By combining photolithography
      and ELD, we were also able to pattern the composite coating into regular arrays
      of squares. Preliminary results by nanoindentation tests showed that properly
      prepared composite coating may have higher elastic modulus and scratch resistance
      than monolithic porous calcium phosphate coating. The results not only provide a
      novel bioactive coating for biomedical implants, but also establish a new
      experimental protocol for studying biomineralization mechanisms of collagen based
      biological tissues.

PMID- 15576137
TI  - Rheometric study of the gelation of chitosan in a hydroalcoholic medium.
AB  - The formation of chitosan physical hydrogels without any external cross-linking
      agent was studied. The gelation took place in an acetic acid-water-propanediol
      solution. The time to reach the gel point was determined by rheometry and
      gelations from different initial conditions could be compared. The influence of
      different parameters on gelation such as the polymer concentration, the degree of
      acetylation (DA) of chitosan and the composition of the initial solvent were
      investigated. The fractal morphology of the sample was not affected by the
      composition of the system. The number of junctions per unit volume at the gel
      point varied only with the initial number of chain entanglements per unit volume.
      Then, below an initial concentration of 1.5% (w/w), physical chain entanglements
      were insufficient and more junctions had to be formed to induce gelation. Over
      this value, only the kinetics allowing to replace entanglements by stable
      physical junctions played a key parameter. This kinetics was influenced by
      several parameters such as DA, temperature or the initial proportion
      water/alcohol. The acetyl groups played an important role in the formation of
      hydrophobic interactions, mainly responsible for gelation. The study of the
      influence of the gelation media revealed two critical points at 40% and 70% of
      water in the initial solvent, probably due to conformational changes and then to
      different modes of gelation. These physical hydrogels being used for cartilage
      regeneration, their final rheological properties were studied as a function of
      their degree of acetylation, the polymer concentration and the solvent
      composition in the initial solvent. Our results allowed us to define an optimal
      gelation condition for our application, corresponding to: DA=40%, a proportion
      water/alcohol of 50/50 and a polymer concentration of 1.5%.

PMID- 15576138
TI  - Laser-induced crystallization of calcium phosphate coatings on polyethylene (PE).
AB  - Calcium phosphate (CaP) coatings are used for obtaining a desired biological
      response. Usually, CaP coatings on metallic substrates are crystallized by
      annealing at temperatures of at least 400-600 degrees C. For polymeric
      substrates, this annealing is not possible due to the low melting temperatures.
      In this work, we present a more suitable method for obtaining crystalline
      coatings on polymeric substrates, namely laser crystallization. We were
      successful in obtaining hydroxyapatite coatings on polyethylene. Because of the
      UV transmission characteristics of the CaP coatings, the use of a low wavelength
      (157 nm) F(2) laser was necessary for this. As a result of the laser treatment,
      the CaP coating broke up into islands. The cracks between the islands became
      larger and the surface became porous with increasing laser energy. The mechanism
      behind the formation of this morphology did not become clear. However, the fact
      that crystalline CaP coatings can be obtained on polymeric substrates in an easy
      way, possibly allows for the development of new products.

PMID- 15576139
TI  - Highly active, lipase silicone elastomers.
AB  - Lipase Candida rugosa was entrapped in silicone rubber via condensation-cure room
      temperature vulcanization of silanol-terminated poly(dimethylsiloxane) with
      tetraethyl orthosilicate as a crosslinker, to give a highly active silicone
      enzyme elastomer. The effect on enzyme activity of addition of water and
      hydrophilic polymeric moieties based on poly(ethylene oxide) 2 was examined, as
      were crosslinker concentration, enzyme concentration, and elastomer thickness. It
      was demonstrated that lipase is most active in silicone elastomers and more
      active in silicone oils than simple hydrocarbons. Crosslink density in these
      elastomers was not an important factor in the reactivity of the rubber. However,
      the addition of hydrophilic species prior to elastomer formation decreased the
      efficiency both of the dispersion of the enzyme and the resulting activity of the
      elastomer. This effect could be moderated by prior exposure of the lipase to
      silicone oil. Thus, hydrophobic silicones play a protective/activating role for
      lipase.

PMID- 15576140
TI  - Effect of pH and ionic strength on the reactivity of Bioglass 45S5.
AB  - Bioglass 45S5 is a silica-based melt-derived glass, used in medical field as a
      bone regenerative material because of the deposition of a layer of hydroxy
      carbonate apatite (HCA) on the surface of the glass when immersed in body fluid.
      The present paper studies the early steps of reaction of 2-microm sized particles
      of Bioglass, in solutions buffered with TRIS at different pH, by means of ICP-ES
      and FTIR spectroscopy. Only at pH 8 could a total reconstruction of the glass be
      observed, with the formation of both a silica and a calcium phosphate rich
      layers. At higher pH, selective dissolution of the glass was hindered by the
      immediate precipitation of a layer of calcium phosphate, whereas at lower pH a
      total breakdown of the glass occurred and no calcium phosphate precipitation was
      noted. The use of the ATR-liquid cell allowed the observation of the reaction in
      real time, and this showed that the process of silica formation is not separable
      from cation leaching from the glass, as well as the formation of the calcium
      phosphate rich layer.

PMID- 15576141
TI  - Photo-polymerized microarchitectural constructs prepared by
      microstereolithography (muSL) using liquid acrylate-end-capped trimethylene
      carbonate-based prepolymers.
AB  - Precision microarchitectural constructs made of acrylated trimethylene carbonate
      (TMC)-based liquid prepolymers were photo-polymerized using a custom-designed
      microstereolithographic apparatus. In this study, three different photo
      polymerizable liquid prepolymers were prepared by the polymerization of TMC with
      a low molecular weight poly(ethylene glycol) (PEG) (mol. wt. 200 or 1000);
      designated as PEG200 or PEG1000, respectively or trimethylolpropane (TMP) as an
      initiator, and subsequently end-capped with an acrylate group. As a result of
      layer-by-layer photo-irradiation of the prepolymer with a movable ultraviolet
      light pen driven by computer-aided design, a three-dimensional (3D) micropillar
      array, a microbank array, a microcone array, and multi-microtunnels formed on a
      platform plate or a glass plate were precisely fabricated. The PEG-based polymers
      exhibited a very low cell adhesion potential, whereas the TMP-based hydrophobic
      polymer exhibited high cell adhesion and proliferation potentials. The microbank
      array, which consisted of a plate made of the TMP-based polymer and microbanks
      made of the PEG200-based polymer, caused cell adhesion and proliferation only on
      the plate. Upon the implantation of microcone arrays under the subcutis of rats,
      the photo-polymerized construct made of the poorly swellable PEG200-based polymer
      exhibited only surface erosion and limited drug loading and releasing potentials.
      On the other hand, the photo-polymerized construct made of the highly swellable
      PEG1000-based polymer exhibited not only surface erosion but also bulk erosion
      and high drug loading and releasing potentials. In this paper, we discuss their
      potential biomedical applications.

PMID- 15576142
TI  - Polymers incorporating nitric oxide releasing/generating substances for improved
      biocompatibility of blood-contacting medical devices.
AB  - The current state-of-the-art with respect to the preparation, characterization
      and biomedical applications of novel nitric oxide (NO) releasing or generating
      polymeric materials is reviewed. Such materials show exceptional promise as
      coatings to prepare a new generation of medical devices with superior
      biocompatiblity. Nitric oxide is a well-known inhibitor of platelet adhesion and
      activation, as well as a potent inhibitor of smooth muscle cell proliferation.
      Hence, polymers that release or generate NO locally at their surface exhibit
      greatly enhanced thromboresistivity and have the potential to reduce neointimal
      hyperplasia caused by device damage to blood vessel walls. In this review, the
      use of diazeniumdiolates and nitrosothiols as NO donors within a variety
      polymeric matrixes are summarized. Such species can either be doped as discrete
      NO donors within polymeric films, or covalently linked to polymer backbones
      and/or inorganic polymeric filler particles that are often employed to enhance
      the strength of biomedical polymers (e.g., fumed silica or titanium dioxide). In
      addition, very recent efforts to create catalytic polymers possessing immobilized
      Cu(II) sites capable of generating NO from endogenous oxidized forms of NO
      already present in blood and other physiological fluids (nitrite and
      nitrosothiols) are discussed. Preliminary literature data illustrating the
      efficacy of the various NO release/generating polymers as coatings for
      intravascular sensors, extracorporeal blood loop circuits, and arteriovenous
      grafts/shunts are reviewed.

PMID- 15576143
TI  - Expression of inflammatory cytokines, RANKL and OPG induced by titanium, cobalt
      chromium and polyethylene particles.
AB  - Bone resorption is regulated by cytokines such as tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1 beta (IL-1beta) and by the balance of a receptor
      activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG). The
      aim of this study was to investigate the mechanism of particle-induced osteolysis
      in murine calvariae by assessing the extent of osteolysis and the expression of
      inflammatory cytokines, RANKL and OPG after implantation of metal and
      polyethylene particles. The murine calvariae implanted with Ti6Al4V, CoCr or high
      density polyethylene (HDP) particles showed significantly more extensive
      osteolysis and elevated levels of inflammatory cytokines. The ratio between RANKL
      and OPG was high in the mice implanted with Ti6Al4V and HDP particles, but not in
      the mice implanted with CoCr particles. These observations suggested that CoCr
      particle-induced osteoclastogenesis may be caused directly by inflammatory
      cytokines rather than by the RANKL-RANK pathway. There might be different
      mechanisms at work in particle-induced osteolysis between Ti6Al4V, HDP and CoCr.

PMID- 15576144
TI  - The response of healing corneal epithelium to grooved polymer surfaces.
AB  - Corneal epithelial wounds heal rapidly by the inwards growth of tissue with a
      contracting wound front. A synthetic polymer lens to correct refractive error (an
      implantable contact lens) could be incorporated into the cornea using this wound
      healing process. Topographical cues on the polymer surface may facilitate
      epithelial tissue migration over the anterior device surface. Here, silicone
      discs with a defined surface geometry of parallel grooves (groove and ridge
      widths of 1, 2, 5 and 10 microm; groove depths of 1 and 5 microm) were implanted
      into corneas and maintained in organ culture. The nature and rate of epithelial
      tissue migration over the test surfaces was monitored for 8 days and evaluated
      using microscopy and histology. Irrespective of the pitch, deep groove geometries
      directed tissue migration laterally along the grooves but this prevented
      contraction of the wound front and retarded migration rates. No guidance occurred
      on any of the shallow groove geometries but these allowed inwards radial
      migration with a contracting wound front and supported migration rates equivalent
      to a flat surface. None of the geometries tested promoted tissue migration above
      a flat polymer surface and data suggested that parallel grooves may not be
      optimal for this application.

PMID- 15576145
TI  - Cytotoxic and mutagenic effects of dental composite materials.
AB  - Mutagenicity of single compounds of dental resinous materials has been
      investigated on many occasions before, but the induction of mutagenic effects by
      extracts of clinically used composites is still unknown. Here, cytotoxic effects
      and the formation of micronuclei were determined in V79 fibroblasts after
      exposure to extracts of modern composite filling materials (Solitaire, Solitaire
      2, Tetric Ceram, Dyract AP, Definite). For cytotoxicity testing, test specimens
      were aged for various time periods (0, 24, and 168 h), and V79 cells were then
      exposed to dilutions of the original extracts for 24, 48, and 72 h. The ranking
      of the cytotoxic effects of the composites according to EC50 values after a 24-h
      exposure period was as follows: Solitaire (most toxic)=Solitaire 2<Tetric
      Ceram<Dyract AP<Definite (least toxic). Cytotoxicity was independent of the
      period of aging for each composite, but varied with exposure periods. The
      cytotoxic effect of Solitaire increased about two-fold between exposure periods
      of 24, 48, and 72 h, no changes were observed with Solitaire 2, and cytotoxicity
      of Tetric Ceram, Dyract AP, and Definite was reduced. Even eight-fold diluted
      original extracts of freshly mixed Solitaire test specimens increased the numbers
      of micronuclei about 10-fold, and Solitaire 2 was slightly less effective. The
      mutagenic effects of these materials were reduced in the presence of a rat liver
      homogenate (S9). Weak increases of the numbers of micronuclei were detected only
      with undiluted extracts of Tetric Ceram and Dyract AP, but Definite was not
      effective. Our findings suggest that mutagenic components of biologically active
      composite resins should be replaced by more biocompatible substances to avoid
      risk factors for the health of patients and dental personnel.

PMID- 15576146
TI  - The effect of non-specific interactions on cellular adhesion using model
      surfaces.
AB  - The contribution of non-specific interactions between cells and model functional
      surfaces was measured using a spinning disc apparatus. These model functional
      surfaces were created using self-assembled monolayers (SAM) of alkylsilanes
      terminated with epoxide, carboxyl (COOH), amine (NH(2)), and methyl (CH(3))
      groups. These SAMs were characterized using ellipsometry, atomic force
      microscopy, contact angle goniometry, and X-ray photoelectron spectroscopy to
      confirm the presence of well-formed monolayers of expected physicochemical
      characteristics. All substrates also demonstrated excellent stability under
      prolonged exposure (up to 18 h) to aqueous conditions. The adhesion strength of
      K100 erythroleukemia cells to the functional substrates followed the trend: CH(3)
      < COOH approximately epoxide << NH(2). The NH(2) SAM surface exhibited nearly an
      order of magnitude greater adhesion strength than the other SAMs and this non
      specific effect exceeded the adhesion measured when RGD tri-peptides were also
      immobilized on the surface. These findings illustrate the importance of substrate
      selection in quantitative studies of peptide-mediated cellular adhesion.

PMID- 15576147
TI  - The influence of different heparin surface concentrations and antithrombin
      binding capacity on inflammation and coagulation.
AB  - The corline heparin surface (CHS) used in the extracorporeal circuit during
      coronary artery bypass grafting is shown to decrease the activation of
      inflammation and coagulation. Synchrotron radiation studies have shown that a
      single layer of the CHS may not completely cover the substrate surface. However,
      a double layer of CHS results in a uniform surface. We investigated the effect of
      surfaces with different surface concentrations of heparin on cell activation and
      coagulation compared to an uncoated surface. The CHS is prepared by a
      conditioning layer of polymeric amine onto which a macromolecular heparin
      conjugate is attached. We used PVC tubing, uncoated or modified with a single or
      double layer of the CHS, and circulated fresh whole blood from healthy volunteers
      in a loop model system at 37 degrees C up to 4 h. Blood was drawn from the loops
      at different times and activation of inflammation and coagulation was studied by
      real-time PCR, flow cytometry and ELISA. The activation of leukocytes and
      platelets and formation of leukocyte-platelet aggregates were reduced by use of
      the single-layered CHS compared to the uncoated surface. Use of double-layered
      CHS resulted in significantly reduced cell activation and thrombin generation.
      Development of the CHS obtained by the double layer of the coating has improved
      the biocompatibility of the surface.

PMID- 15576148
TI  - Long-term in vivo biomechanical properties and biocompatibility of poly(2
      hydroxyethyl methacrylate-co-methyl methacrylate) nerve conduits.
AB  - Artificial grafts are promising alternatives to nerve grafts for peripheral nerve
      repair because they obviate the complications and disadvantages associated with
      autografting such as donor site morbidity and limited tissue availability. We
      have synthesized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA
      MMA) porous tubes and studied their efficacy in vivo. Specifically, we studied
      the short- and long-term stability and biocompatibility of 12 mm long tubes for
      the repair of surgically created 10 mm nerve gaps in rat sciatic nerves. Prior to
      implantation, tubes were analyzed in vitro using a micro-mechanical tester to
      measure displacement achieved with load applied. These results served as a
      calibration curve, y = 6.8105 x -0.0073 (R2 = 0.9750, n = 28), for in vivo
      morphometric tube compression measurements. In vivo, most of the PHEMA-MMA
      conduits maintained their structural integrity up to 8 weeks, but 29% (4/14) of
      them collapsed by 16 weeks. Interestingly, the tube wall area of collapsed 16
      week tubes was significantly lower than those of patent tubes. Tubes were largely
      biocompatible; however, a small subset of 16-week tubes displayed signs of
      chronic inflammation characterized by "finger-like" tissue extensions invading
      the inner tube aspect, inflammatory cells (some of which were ED1+macrophages)
      and giant cells. Tubes also demonstrated signs of calcification, which increased
      from 8 to 16 weeks. To overcome these issues, future nerve conduits will be re
      designed to be more robust and biocompatible.

PMID- 15576149
TI  - Changes in the distribution of laminin-5 during peri-implant epithelium formation
      after immediate titanium implantation in rats.
AB  - Laminin-5 (Ln-5), a component of the basement membrane (BM), regulates epithelial
      cell migration and adhesion. This study used anti-Ln-5 (gamma2chain) antibody to
      investigate the distribution of Ln-5 during the formation of peri-implant
      epithelium (PIE) in rats, and compared it to the distribution of Ln-5 during oral
      mucosa formation after tooth extraction. One day after extraction, the junctional
      epithelium (JE) had disappeared. After 3 days, new epithelium formed from the
      oral sulcular epithelium (OSE) and extended horizontally over the wound with Ln-5
      positive cells at the leading edge. After 5 days, the epithelium extending from
      the OSE on each side of the wound joined and formed additional new epithelium.
      The new epithelium expressed Ln-5 in the BM. After 1-2 weeks, the oral epithelium
      (OE) extending from the sides of the wound joined in the center. Thereafter, OSE
      and new epithelium disappeared, and only OE remained covering the wound. Three
      days after implantation (titanium), no JE remained. New epithelium formed from
      the keratinized OSE extending apically with Ln-5-positive cells. After 1-2 weeks,
      the new epithelium became the PIE and spread further apically facing the implant
      surface. Ln-5 was expressed at the PIE-connective tissue interface, but not at
      the implant-PIE interface. Finally, after 4 weeks, Ln-5 was expressed at the
      implant-PIE interface, and the PIE was non-keratinized epithelium. These findings
      suggest that Ln-5 induces cell migration during PIE formation, and that PIE
      originates from OSE. Furthermore, they support the hypothesis that Ln-5
      contributes to the attachment of PIE to titanium, regardless of the delay in the
      synthesis and deposition of Ln-5 at the titanium-PIE interface.

PMID- 15576150
TI  - Physicochemical characterisation and biological evaluation of hydrogel
      poly(epsilon-caprolactone) interpenetrating polymer networks as novel urinary
      biomaterials.
AB  - Hydrogels are frequently employed as medical device biomaterials due to their
      advantageous biological properties, e.g. resistance to infection and
      encrustation, biocompatibility; however, their poor mechanical properties
      generally limit the scope of application to coatings of medical devices. To
      address this limitation, this study described the formulation of sequential
      interpenetrating polymer networks (IPN) of poly(-caprolactone) (PCL) and
      poly(hydroxyethylmethacrylate) (p(HEMA)). IPN containing 20% w/w PCL, p(HEMA),
      both in the presence or absence of ethyleneglycol dimethacrylate (EGDMA 1% w/w),
      were prepared by free radical polymerisation. Following preparation the
      degradation and the mechanical and surface properties of the biomaterials and, in
      addition, the resistances to microbial adherence and encrustation in vitro were
      examined. In comparison to p(HEMA) the various IPN exhibited substantially
      greater tensile properties (ultimate tensile strength, % elongation, Young's
      modulus) that were accredited to the discrete distribution of PCL within the
      hydrogel network. The IPN exhibited two glass transition temperatures that were
      statistically similar to those of the individual components, thereby providing
      evidence of the immiscible nature of the two polymers. The IPN possessed higher
      receding contact angles and lower equilibrium water contents in comparison to
      p(HEMA), whereas the limited degradation of the IPN at both pH 7 and 9 was deemed
      suitable for clinical usage for periods of at least 4 weeks. The resistances of
      the various IPN to bacterial adherence and urinary encrustation were examined
      using in vitro models. Importantly the resistance of the IPN to encrustation was,
      in general, similar to that of p(HEMA) but greater than that of PCL whereas, the
      resistance of the IPN to bacterial adherence was frequently greater than that of
      p(HEMA) and PCL. Therefore, this study has shown that the mechanical properties
      of p(HEMA) may be substantially increased by the formation of IPN with PCL whilst
      maintaining other appropriate physicochemical properties and resistances to
      urinary encrustation and bacterial adherence. It is suggested that these IPN may
      be suitable for device fabrication thereby expanding the manufacturing
      application of hydrogels without compromising their potential clinical efficacy.

PMID- 15576151
TI  - Retention of transforming growth factor beta1 using functionalized dextran-based
      hydrogels.
AB  - Functionalized dextrans (FD) are anionic water-soluble polymers bearing
      carboxylate, benzylamide and sulfate groups, which exhibit binding capacity to
      transforming growth factor-beta1 (TGF-beta1). In this paper, we have investigated
      the ability of dextran-based hydrogels containing FD, to bind and release
      recombinant human TGF-beta1. Hydrogels were prepared by chemical crosslink native
      dextran and FD with sodium trimetaphosphate in 1m NaOH at 50 degrees C. A wide
      range of hydrogels were prepared as particles ranging of 1-1.6mm of diameter and
      characterized with various amounts of FD and with different crosslinker feeding
      ratios (CFR). Dried particles were soaked with recombinant human transforming
      growth factor-beta1 (rhTGF-beta1) to determine their capacity to deliver the
      growth factor. Results indicated that the in vitro kinetics releases of rhTGF
      beta1 were related to FD and CFR. Retention capacity of rhTGF-beta1 increases
      with an increase of negative charges of the matrices brought by both phosphate
      linkages and FD as demonstrated by an additional release of growth factor in high
      ionic strength solution. Highly crosslinked hydrogels that contained the highest
      amount of FD (18% (w/w)) retained up to 88% of rhTGF-beta1. Bioactivity of
      released growth factor was confirmed in a cell assay. These functionalized
      hydrogels may have important uses for the stabilization and the protection of
      rhTGF-beta1 as entrapment systems and could be applied to other proteins of
      clinical interest.

PMID- 15576152
TI  - Tissue response to partially in vitro predegraded poly-L-lactide implants.
AB  - The in vivo local reaction of as-polymerized poly-L-lactide composed of 96% L
      lactide and 4% D-lactide (PLA96) was investigated by histology at 2, 13 and 26
      weeks after subcutaneous implantation in rats. In order to simulate possible end
      stage reactions the PLA96 was also predegraded in vitro until approximately 50%
      weight loss. The local reaction of predegraded PLA (PLA96(168)) was compared to
      the local reaction of polyethylene (PE) and non-predegraded PLA (PLA96). For PE
      and PLA96 a mild local reaction was observed at all time points consisting of a
      minimal layer of macrophage like cells with incidentally multinucleated giant
      cells at the implant interface, surrounded by a mild connective tissue capsule.
      For PLA96 at weeks 13 and 26 some minimal alterations in terms of degradation and
      ingrowth of cells was noted. The in vitro incubation (90 degrees C for 168 h) of
      PLA96(168) resulted for the thin 0.2 mm samples in complete degradation.
      Predegraded 0.5, 1.0 and 2.0 mm PLA96(168) samples were implanted and evaluated.
      The 1.0 and 2.0 mm samples could be evaluated for all time points investigated,
      but some 0.5 mm PLA96(168) samples were already completely resorbed at week 2
      after implantation. In general, responses found for the predegraded PLA96(168) at
      weeks 2, 13 and 26 were similar with a pronounced macrophage infiltrate
      containing birefringent material, encapsulation of polymer fragments, and the
      presence of a debris area consisting of polymer and cellular remnants. In lymph
      nodes foamy macrophages with birefringent material were only observed in lymph
      nodes draining sites with predegraded PLA96(168). Immunohistochemistry was
      performed for further characterization of the cellular infiltrate. At the implant
      interface of the non-degrading PE and PLA96, ED1 and OX6 (MHC class II) positive
      cells were identified. In the capsule macrophage like cells expressed all three
      macrophage markers ED1, ED2, and ED3. CD4 and CD8 positive cells, indicating T
      helper and T supressor/cytotoxic cells, respectively, could be observed in low
      numbers, CD4 more than CD8. Both CD4 and CD8 were occasionally observed within
      the degrading PLA96(168) implant. Polymorphonuclear neutrophilic granulocytes
      were mainly observed at 2 weeks after implantation. We showed that predegradation
      could be used as a means to study late tissue reactions to polymers. Complete
      degradation may be studied with relatively thin implants, but this may lead to
      rather optimistic interpretation of resorption periods. When materials are
      intended to be used for screws and/or plates for bone fixation, implants of at
      least 1.0-2.0 mm thickness should be used as these may show a more realistic
      representation of the resorption characteristics of the material under
      investigation.

PMID- 15576153
TI  - Comparative study of osteoconduction on micromachined and alkali-treated titanium
      alloy surfaces in vitro and in vivo.
AB  - This study sought to evaluate osteoconduction of Ti-6Al-4V surfaces under various
      conditions, including micro-patterned, alkali-treated, micro-patterned plus
      alkali-treated, and surfaces without any treatment as the control. The through
      mask electrochemical micromachining (EMM) was used to fabricate micro-hole arrays
      on the titanium alloy surface. In vitro calcium phosphate formation on titanium
      surfaces was in static and dynamic simulated body fluid (SBF). In vivo comparison
      was conducted in the medullary cavity of dog femur using the implant cages which
      could provide the same physiological environment for specimens with different
      surface conditions. In vitro experiments indicate good conduction of calcium
      phosphate on the alkali-treated surfaces, and also better calcium phosphate
      deposition on the micro-hole surface than on the flat surfaces in dynamic SBF. In
      vivo experiments confirm the beneficial effect of alkaline treatment on
      osteoconduction. The results of in vivo experiments also indicate a synergistic
      effect of the alkaline treatment and the topographic pattern on osteoconduction.

PMID- 15576154
TI  - The decrease of particle-induced osteolysis after a single dose of
      bisphosphonate.
AB  - The most common cause of implant failure in joint replacement is aseptic
      loosening due to particle-induced osteolysis. Bisphosphonates have been shown to
      be effective against particle-induced osteolysis when administered daily. We
      investigated the effect of a single subcutaneous dose of a more potent third
      generation bisphosphonate on particle-induced osteolysis. We utilized the murine
      calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured as
      resorption within the midline suture using Giemsa staining. Twenty-eight mice
      were used, seven per group. Seven animals were treated with a single dose of
      zoledronic acid (ZA) directly after surgery and seven animals were treated four
      days postoperatively. For statistical analysis one-way ANOVA and a Student's t
      test were used. Bone resorption was 0.26+/-0.09 mm(2) in animals with particle
      implantation, 0.14+/-0.05 mm(2) in animals with particle implantation and ZA
      treatment directly after surgery (p = 0.0047), and 0.15+/-0.05 mm(2) in animals
      with particle implantation and ZA treatment on the fourth postoperative day (p =
      0.006). In conclusion, particle-induced bone resorption was markedly decreased by
      a single s.c. dose of a third generation bisphosphonate. This important new
      finding holds great promise, because single dose treatment of particle-induced
      osteolysis may reduce side effects compared to repeated application of
      bisphosphonates.

PMID- 15576155
TI  - Spatially resolved photopolymerization kinetics and oxygen inhibition in dental
      adhesives.
AB  - A comparative study of three commercial dental adhesives was performed by (1)H
      nuclear magnetic resonance spectroscopy and Stray-Field magnetic resonance
      imaging. Spectroscopic evidence was found for the presence of solvent and
      unreacted methacrylate groups in photopolymerized adhesives. Spatially resolved
      photopolymerization kinetics and volumetric contraction (solvent evaporation and
      polymerization shrinkage) were obtained without solvent removal and in the
      presence of oxygen from the atmosphere. The oxygen and solvent inhibitor effects
      in the photopolymerization were found to be higher for water/ethanol based
      adhesives. However, was one of these adhesives that exhibited less spatially
      dependent irradiation time to start vitrification, higher concentration and a
      more uniform spatial distribution of rigid domains at the end of the
      photopolymerization.

PMID- 15576156
TI  - Plasma transglutaminase factor XIII induces microvessel ingrowth into
      biodegradable hydroxyapatite implants in rats.
AB  - Coagulation factor XIII is a member of the transglutaminase-family.
      Transgluaminases cross-link either fibrin monomers in blood coagulation or
      extracellular proteins in extracellular matrix formation. In early stages of bone
      healing migration and proliferation of endothelial cells lead to formation of new
      vessels. The aim of this study was to investigate the angiogenetic activity of
      plasma factor XIII in bone defects filled with nanoparticulate hydroxyapatite
      paste. A critical size defect was created in the tibial head of rats which was
      not filled in group I. In group II the defect was filled with hydroxyapatite
      paste, and in group III with hydroxyapatite paste enriched with factor XIII. Ten
      days after surgery angiogenesis in the defects was assessed using
      immunohistochemistry and confocal laser scanning microscopy. Ac16 antibody was
      used to detect activation of factor XIII into factor XIIIA. In defects without
      biomaterial (group I) vessel-rich connective tissue and diffuse distribution of
      capillaries was observed. In defects filled with pure hydroxyapatite (group II)
      formation of capillaries was limited to the host bone-hydroxyapatite interface.
      In contrast, addition of plasma factor XIII to hydroxyapatite (group III)
      stimulated formation of vessels within the biomaterial. The current study reveals
      that factor XIII can improve angiogenesis in hydroxyapatite.

PMID- 15576157
TI  - Ectopic bone formation in rats: the importance of the carrier.
AB  - Much research has been done to develop the ideal bone graft substitute (BGS). One
      approach to develop this ideal BGS is the use of growth factors, but for this
      approach osteoprogenitor cells are needed at the site of reconstruction. An
      alternative is a cell-based approach, where enough cells are provided to form
      bone in a carrier material. In previous studies of our group, titanium (Ti)
      carriers have been used, because of the excellent mechanical properties and the
      bone-compatibility of this material. On the other hand, calcium phosphate (CaP)
      ceramics are known for their excellent osteoconductivity. The aim of this study
      is to investigate the influence of the carrier in a cell-based bone regeneration
      approach, whereby we hypothesize that CaP-ceramic implants will induce more bone
      formation than Ti-fiber implants, in the same animal model as our previous
      experiment. Ti-fiber mesh implants and ceramic implants were seeded with rat bone
      marrow cells (RBM) and implanted subcutaneously. Histological analysis after one,
      three and six weeks showed differences in the way of bone formation in the two
      groups: bone appeared to grow from the center to the periphery of the implant in
      the titanium group, while bone formation in the ceramic group occurred through
      the whole implant. Histomorphometrical analysis after one week showed very
      limited bone formation for both the titanium and ceramic group. At three weeks,
      the amount of bone formation was increased till about 10% for the titanium group
      and 18% for the ceramic group. No significant difference between the two groups
      could be observed. In the six week group, the bone formation was 6% (Ti) and 23%
      (CaP), respectively (P < 0.001). Further, bone formation started earlier in the
      CaP-ceramic scaffolds than in the Ti scaffolds. Our hypothesis could be
      confirmed: ceramic implants induce more bone formation than titanium implants.

PMID- 15576158
TI  - Differential regulation of osteoblasts by substrate microstructural features.
AB  - Microtextured titanium implant surfaces enhance bone formation in vivo and
      osteoblast phenotypic expression in vitro, but the mechanisms are not understood.
      To determine the roles of specific microarchitectural features in modulating
      osteoblast behavior, we used Ti surfaces prepared by electrochemical
      micromachining as substrates for MG63 osteoblast-like cell culture. Cell response
      was compared to tissue culture plastic, a sand-blasted with large grit and acid
      etched surface with defined mixed microtopography (SLA), polished Ti surfaces,
      and polished surfaces electrochemically machined through a photoresist pattern to
      produce cavities with 100, 30 and 10 microm diameters arranged so that the ratio
      of the microscopic-scale area of the cavities versus the microscopic-scale area
      of the flat region between the cavities was equal to 1 or 6. Microstructured
      disks were acid-etched, producing overall sub-micron-scale roughness (Ra=0.7
      microm). Cell number, differentiation (alkaline phosphatase; osteocalcin) and
      local factor levels (TGF-beta1; PGE(2)) varied with microarchitecture. 100 microm
      cavities favored osteoblast attachment and growth, the sub-micron-scale etch
      enhanced differentiation and TGF-beta1 production, whereas PGE(2) depended on
      cavity dimensions but not the sub-micron-scale roughness.

PMID- 15576159
TI  - Prevention of the epoxy resin-based root canal sealers-induced cyclooxygenase-2
      expression and cytotoxicity of human osteoblastic cells by various antioxidants.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme believed to be responsible for
      prostaglandin synthesis at the site of inflammation. Recently, the activation of
      COX-2 expression may be one of the important pathogenesis of root canal sealers
      induced periapical inflammation. However, little is known about whether chemical
      interaction can modulate the epoxy resin-based root canal sealers-induced
      cytotoxicity as well as COX-2 expression. The aim of the present study was to
      investigate the effects of antioxidants catalase, superoxide dismutase (SOD), and
      N-acetyl-L-cysteine (NAC) on AH26- and Topseal-induced COX-2 mRNA gene and
      cytotoxicity in human osteoblastic cell line U2OS cells. The results showed that
      both epoxy resin-based root canal sealers were cytotoxic to U2OS cells in a
      concentration-dependent manner (p<0.05). AH26 and Topseal were found to induce
      COX-2 mRNA gene expression in U2OS cells. The addition of glutathione (GSH)
      precursor NAC led to decrease the induction of COX-2 mRNA gene expression and
      cytotoxicity by both AH26 and Topseal (p<0.05). However, catalase and SOD lacked
      the ability to prevent AH26-and Topseal-induced cytotoxicity and COX-2 mRNA gene
      expression (p>0.05). Taken together, the activation of COX-2 mRNA gene expression
      may be one of the pathogenesis of epoxy resin-based root canal sealers-induced
      periapical inflammation. In addition, GSH depletion, but not the attack of oxygen
      free radicals, could be the mechanism for epoxy resin-based root canal sealers
      induced cytotoxicity and COX-2 mRNA gene expression. Factors that induce GSH
      synthesis may appear useful in preventing cell damage mediated by epoxy resin
      based root canal sealers.

PMID- 15576160
TI  - The roles of tissue engineering and vascularisation in the development of micro
      vascular networks: a review.
AB  - The construction of tissue-engineered devices for medical applications is now
      possible in vitro using cell culture and bioreactors. Although methods of
      incorporating them back into the host are available, current constructs depend
      purely on diffusion which limits their potential. The absence of a vascular
      network capable of distributing oxygen and other nutrients within the tissue
      engineered device is a major limiting factor in creating vascularised artificial
      tissues. Though bio-hybrid prostheses such as vascular bypass grafts and skin
      substitutes have already been developed and are being used clinically, the
      absence of a capillary bed linking the two systems remains the missing link. In
      this review, the different approaches currently being or that have been applied
      to vascularise tissues are identified and discussed.

PMID- 15576161
TI  - Growth of human cells on polyethersulfone (PES) hollow fiber membranes.
AB  - A novel material of porous hollow fibers made of polyethersulfone (PES) was
      examined for its ability to support the growth of human cells. This material was
      made in the absence of solvents and had pore diameters smaller than 100 microm.
      Human cell lines of different tissue and cell types (endothelial, epithelial,
      fibroblast, glial, keratinocyte, osteoblast) were investigated for adherence,
      growth, spread and survival on PES by confocal laser microscopy after staining of
      the cells with Calcein-AM. Endothelial cell attachment and growth required pre
      coating PES with either fibronectin or gelatin. The other cell types exhibited
      little difference in growth, spread or survival on coated or uncoated PES. All
      the cells readily adhered and spread on the outer, inner and cut surfaces of PES.
      With time confluent monolayers of cells covered the available surface area of PES
      and in some cases cells grew as multilayers. Many of the cells were able to
      survive on the PES for up to 7 weeks and in some cases growth was so extensive
      that the underlying PES was no longer visible. Scanning electron microscope
      observations of cells on the materials correlated with the confocal morphometric
      data. Thus, PES is a substrate for the growth of many different types of human
      cells and may be a useful scaffolding material for tissue engineering.

PMID- 15576162
TI  - The use of patterned dual thermoresponsive surfaces for the collective recovery
      as co-cultured cell sheets.
AB  - Heterotypic cell interactions are critical to achieve and maintain specific
      functions in many tissues and organs. We have focused on patterned structure
      surfaces to enable co-culture of heterotypic cells and recovery of patterned co
      cultured cell sheets for applications in tissue engineering. Thermoresponsive
      polymers exhibiting different transition temperatures in water comprise both
      poly(N-isopropylacrylamide) (PIPAAm) and n-butyl methacrylate (BMA) co-grafted as
      side chains to PIPAAm main chains. These copolymers were surface-grafted in
      patterns to obtain patterned dual thermoresponsive cell culture surfaces using
      electron beam polymerisation method and porous metal masks. On patterned
      surfaces, site-selective adhesion on and growth of rat primary hepatocytes (HCs)
      and bovine carotid endothelial cells (ECs) allowed patterned co-culture,
      exploiting hydrophobic/hydrophilic surface chemistry regulated by culture
      temperature as the sole variable. At 27 degrees C, seeded HCs adhered exclusively
      onto hydrophobic, dehydrated P(IPAAm-BMA) co-grafted domains (1-mm laser dot),
      but not onto neighbouring hydrated PIPAAm domains. Sequentially seeded ECs then
      adhered exclusively to hydrophobised PIPAAm domains upon increasing culture
      temperature to 37 degrees C, achieving patterned co-cultures. Reducing culture
      temperature to 20 degrees C promoted hydration of both polymer-grafted domains,
      permitting release of the co-cultured, patterned cell monolayers as continuous
      cell sheets with heterotypic cell interactions. Recovered co-cultured cell sheets
      can be manipulated, moved and sandwiched with other structures, providing new
      useful constructs both for basic cell biology research and preparation of tissue
      mimicking multi-layer materials through overlaying co-cultured cell sheets.

PMID- 15576163
TI  - Activation of membrane receptors by a neurotransmitter conjugate designed for
      surface attachment.
AB  - The derivatization of surfaces with bioactive molecules is a research area of
      growing importance for cell and tissue engineering. Tetherable molecules used in
      such applications must contain an anchoring moiety as well as the biofunctional
      group, typically along with a spacer to prevent steric clashes between the target
      molecule and the tethering surface. Post-synaptic membrane receptors at chemical
      synapses in neural tissue mediate signaling to the post-synaptic neuron and are
      activated by the binding of diffusible neurotransmitter molecules released by the
      pre-synaptic neuron. However, little attention has been directed at developing
      neurotransmitter analogs that might retain functionality when tethered to a
      surface that could be interfaced with post-synaptic receptor proteins. Muscimol
      (5-aminomethyl-3-hydroxyisoxazole), an analog of GABA (gamma-aminobutryic acid),
      is a known potent agonist of GABA(A) and GABA(C) post-synaptic receptors found in
      retina and other central nervous system tissue. The present paper reports
      experiments testing the electrophysiological activity of "muscimol-biotin" on
      cloned GABA receptors expressed in Xenopus oocytes. This compound, which is
      potentially suitable for tethering at avidin-coated surfaces, consists of
      muscimol conjugated through an N-acyl linkage to a 6-aminohexanoyl chain that is
      distally terminated by biotin. We find that muscimol-biotin, as well as a
      structurally similar compound (muscimol-BODIPY) containing a bulky fluorophore at
      the distal end of the aminohexanoyl chain, exhibits substantial agonist activity
      at GABA(A) and GABA(C) receptors. Muscimol-biotin and other similarly
      biotinylated neurotransmitter analogs, in combination with surface
      functionalization using avidin-biotin technology, may be useful in applications
      involving the controlled activation of neuronal post-synaptic receptors by
      surface-attached molecules.

PMID- 15576164
TI  - Construction of varying porous structures in acellular bovine pericardia as a
      tissue-engineering extracellular matrix.
AB  - In the study, a cell extraction process was used to remove the cellular
      components from bovine pericardia. Varying pore sizes and porosities of the
      acellular tissues were then created using acetic acid and collagenase and
      subsequently fixed with genipin. Biochemical analyses found that these acellular
      tissues with distinct porous structures consisted primarily of insoluble
      collagen, elastin, and tightly bound glycosaminoglycans. The thermal stability,
      mechanical properties, and capability against enzymatic degradation of the bovine
      pericardial tissue remained unaltered after cell extraction. However, following
      further treatment with acetic acid and collagenase, the thermal stability and
      capability against enzymatic degradation of the acellular tissues declined. The
      porous structures of the implanted samples seem to determine whether successful
      microvessel-ingrowth takes place. The acetic-acid- and collagenase-treated
      tissues, due to their high pore size and porosity, showed a large number of
      microvessels infiltrating into the interstices of the implanted samples. In
      contrast, a low density of microvessels was observed infiltrating into the
      acellular tissue and penetration of microvessels into the cellular tissue was
      never encountered.

PMID- 15576165
TI  - Vascular patches tissue-engineered with autologous bone marrow-derived cells and
      decellularized tissue matrices.
AB  - Synthetic polymer vascular patches used in cardiovascular surgery have
      shortcomings such as thrombosis, intimal hyperplasia, calcification, infection,
      and no growth potential. Tissue-engineered vascular patches using autologous
      vascular cells may solve these problems. In this study, we developed a tissue
      engineered vascular patch using autologous bone marrow-derived cells (BMCs) and
      decellularized tissue matrices. Vascular smooth muscle cells and endothelial
      cells were differentiated from bone marrow mononuclear cells in vitro. Tissue
      engineered vascular patches were fabricated by seeding these cells onto
      decellularized canine inferior vena cava matrices and implanted into the inferior
      vena cava of dogs. Three weeks after implantation, the tissue-engineered vascular
      patches were patent with no sign of thrombus formation. Histological,
      immunohistochemical, and electron microscopic analyses of the vascular patches
      retrieved 3 weeks after implantation revealed regeneration of endothelium and
      smooth muscle and the presence of collagen and elastin. BMCs labeled with a
      fluorescent dye prior to implantation were detected in the retrieved vascular
      patches, indicating that the BMCs survived after implantation and contributed to
      the vascular tissue regeneration. This study demonstrates that vascular patches
      can be tissue-engineered with autologous BMCs and decellularized tissue matrices.

PMID- 15576166
TI  - Hyaluronic acid modified biodegradable scaffolds for cartilage tissue
      engineering.
AB  - Hyaluronic acid (hyaluronan, HA) was immobilized onto the surface of macroporous
      biodegradable poly(D,L-lactic acid-co-glycolic acid) [PLGA] scaffolds to enhance
      the attachment, proliferation, and differentiation of chondrocytes for cartilage
      tissue engineering. The PLGA scaffolds were prepared by blending PLGA with
      varying amounts of amine-terminated PLGA-PEG di-block copolymer. They were
      fabricated by a gas foaming/salt leaching method. HA was chemically conjugated to
      the surface-exposed amine groups on the pre-fabricated scaffolds. The amount of
      surface exposed free amine groups was quantitatively determined by conjugating an
      amine-reactive fluorescent dye to the PLGA blend films. The extent of HA
      immobilization was also confirmed by measuring water contact angles. When
      chondrocytes were seeded within HA modified PLGA scaffolds, enhanced cellular
      attachment was observed compared to unmodified PLGA scaffolds. Furthermore,
      glycosaminoglycan and total collagen synthesis increased substantially for HA
      modified PLGA scaffolds. RT-PCR result and histological examination of the
      resultant cartilage tissue revealed that HA modified scaffolds excelled in
      inducing cartilage tissue formation in terms of collagen type II expression and
      tissue morphological characteristics.

PMID- 15576167
TI  - The effect of bioactive glass content on synthesis and bioactivity of composite
      poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering.
AB  - Tissue engineering offers a promising new approach to bone tissue grafting. One
      material that has received attention in this regard is the polymer poly (lactic
      co-glycolic acid) (PLGA). It has the advantage of controllable bioresorption and
      ease of processing. Another material of interest is bioactive glass (BG), which
      shows the ability to stimulate osteoblastic differentiation of osteoprogenitor
      cells. In this study, we reported on the optimal synthesis parameters and the
      kinetics of formation of calcium phosphate (Ca-P) phase at the surface of PLGA/BG
      composites. The formation of calcium phosphate layer was confirmed using scanning
      electron microscopy/energy dispersive X-ray analysis (SEM/EDXA). PLGA-30%BG
      microspheres based porous scaffolds for bone tissue engineering were examined for
      their ability to promote osteogenesis of marrow stromal cells (MSC). This porous
      scaffold supported both MSC proliferation and promoted MSC differentiation into
      cells expressing the osteoblast phenotype. It therefore demonstrates significant
      potential as a bone replacement material.

PMID- 15576168
TI  - Poly(lactide-co-glycolide) microspheres as a moldable scaffold for cartilage
      tissue engineering.
AB  - This study demonstrates the use of biodegradable poly(lactide-co-glycolide) (PLG)
      microspheres as a moldable scaffold for cartilage tissue engineering.
      Chondrocytes were delivered to a cylindrical mold with or without PLG
      microspheres and cultured in vitro for up to 8 weeks. Cartilagenous tissue formed
      using chondrocytes and microspheres maintained thickness, shape, and chondrocyte
      collagen type II phenotype, as indicated by type II collagen staining. The
      presence of microspheres further enhanced total tissue mass and the amount of
      glycosaminoglycan that accumulated. Evaluation of microsphere composition
      demonstrated effects of polymer molecular weight, end group chemistry, and buffer
      inclusion on tissue-engineered cartilage growth. Higher molecular weight PLG
      resulted in a larger mass of cartilage-like tissue formed and a higher content of
      proteoglycans. Cartilage-like tissue formed using microspheres made from low
      molecular weight and free carboxylic acid end groups did not display increases in
      tissue mass, yet a modest increased proteoglycan accumulation was detected.
      Microspheres comprised of PLG with methyl ester end groups yielded a steady
      increase in tissue mass, with no real increase in matrix accumulation. The
      microencapsulation of Mg(OH)(2) had negative effects on tissue mass and matrix
      accumulation. The data herein reflect the potential utility of a moldable PLG
      chondrocyte system for tissue-engineering applications.

PMID- 15576169
TI  - Effect of human platelet supernatant on proliferation and matrix synthesis of
      human articular chondrocytes in monolayer and three-dimensional alginate
      cultures.
AB  - Articular cartilage is rich in collagen type II fibres and proteoglycans and is
      characterized by low cell density. Chondrocytes have specific nutritional
      requirements and therefore cannot be expanded in vitro without the risk of
      generating fibroblastoid cells expressing type I collagen. Therefore, various
      growth conditions were tested for cartilage tissue engineering. Human platelets
      are a rich source of many growth factors including transforming growth factor
      beta and platelet-derived growth factor. To investigate the effect of human
      platelet supernatant (hPS) on chondrocyte proliferation and differentiation,
      human articular biopsies obtained from three healthy donors. Chondrocytes were
      isolated and expanded separately in monolayer cultures and seeded in alginate
      beads in the presence and absence of hPS of 1% or 10% v/v concentration.
      Transcript levels of genes encoding chondrogenic factors were determined by
      quantitative reverse transcriptase-polymerase chain reaction. The deposition of
      types I and II collagen as well as proteoglycan was detected by indirect
      immunocytochemistry. Addition of hPS activated chondrocyte proliferation in
      monolayer cultures but induced a dedifferentiation of chondrocytes towards a
      fibroblast-like phenotype. The expression levels of mRNAs encoding type II
      collagen, aggrecan and bone morphogenetic protein-2 were reduced in all samples
      tested. Seeding chondrocytes in alginate beads in the presence of hPS generated a
      cell population capable of type II collagen expression, even though hPS induced
      considerable type I collagen expression as well. Differences (1% vs. 10% group,
      1% vs. control, 10% vs. control) in the quantitative gene expression of types I
      and II collagen or of aggrecan were statistically significant (p<0.001). We
      conclude that addition of hPS may accelerate chondrocyte expansion but can lead
      to their dedifferentiation.

PMID- 15576170
TI  - Study of gelatin-containing artificial skin V: fabrication of gelatin scaffolds
      using a salt-leaching method.
AB  - Porous gelatin scaffolds were prepared using a salt-leaching method and these
      were compared to scaffolds fabricated using a freeze-drying method. The salt
      leached gelatin scaffolds were easily formed into desired shapes with a uniformly
      distributed and interconnected pore structure with an average pore size of around
      350 microm. The mechanical strength and the biodegradation rate of the scaffolds
      increased with the porosity, and were easily modulated by the addition of salt.
      After 1 week of in vitro culturing, the fibroblasts in salt-leached scaffolds
      were mainly attached on the surface of the pores in the scaffold, whereas cells
      seeded on freeze-dried scaffolds were widely distributed and aggregated on the
      top and the bottom of the scaffold. After 14 d of culturing, the fibroblasts
      showed a good affinity to, and proliferation on, the gelatin scaffolds without
      showing any signs of biodegradation. An in vivo study of cultured artificial
      dermal substitutes showed that an artificial dermis containing the fibroblasts
      enhanced the re-epithelialization of a full-thickness skin defect when compared
      to an acellular scaffold after 1 week.

PMID- 15576171
TI  - Peptide-immobilized nanoporous alumina membranes for enhanced osteoblast
      adhesion.
AB  - Bone tissue engineering requires the ability to regulate cell behavior through
      precise control over substrate topography and surface chemistry. Understanding of
      the cellular response to micro-environment is essential for biomaterials and
      tissue engineering research. This research employed alumina with porous features
      on the nanoscale. These nanoporous alumina surfaces were modified by physically
      adsorbing vitronectin and covalently immobilizing RGDC peptide to enhance
      adhesion of osteoblasts, bone-forming cells. X-ray photoelectron spectroscopy
      (XPS) and scanning electron microscopy (SEM) were used to characterize the
      modified nanoporous alumina surface. Survey and high-resolution C1s scans
      suggested the presence of RGDC and vitronectin on the surface and SEM images
      confirmed the pores were not clogged after modification. Cell adhesion on both
      unmodified and modified nanoporous alumina was compared using fluorescence
      microscopy and SEM. RGDC was found to enhance osteoblast adhesion after 1 day of
      culture and matrix production was visible after 2 days. Cell secreted matrix was
      absent on unmodified membranes for the same duration. Vitronectin-adsorbed
      surfaces did not show significant improvement in adhesion over unmodified
      membranes.

PMID- 15576172
TI  - Bone tissue engineering on patterned collagen films: an in vitro study.
AB  - This study aimed at guiding osteoblast cells from rat bone marrow on chemically
      modified and patterned collagen films to study the influence of patterns on cell
      guidance. The films were stabilized using different treatment methods including
      crosslinking with carbodiimide (EDC) and glutaraldehyde, dehydrothermal treatment
      (DHT), and deposition of calcium phosphate on the collagen membrane. Mesenchymal
      osteoprogenitor cells were differentiated into osteoblasts and cultured for 7 and
      14 days on micropatterned (groove width: 27 microm, groove depth: 12 microm,
      ridge width: 2 microm) and macropatterned (groove width: 250 microm, groove
      depth: 250 microm, ridge width: 100 microm) collagen films to study the influence
      of pattern dimensions on osteoblast alignment and orientation. Fibrinogen was
      added to the patterned surfaces as a chemical cue to induce osteoblast adhesion.
      Cell proliferation on collagen films was determined using MTS assay. Deposition
      of calcium phosphate on the surface of the film increased surface hydrophilicity
      and roughness and allowed a good cell proliferation. Combined DHT and EDC
      treatment provided an intermediate wettability, and also promoted cell
      proliferation. Glutaraldehyde crosslinking was found to lead to the lowest cell
      proliferation but fibrinogen adsorption on glutaraldehyde treated film surfaces
      increased the cell proliferation significantly. Macropatterns were first tested
      for alignment and only microscopy images were enough to see that there is no
      specific alignment. As a result of this, micropatterned samples with the
      topography that affect cell alignment and guidance were used. Osteoblast
      phenotype expression (ALP activity) was observed to be highest in calcium
      phosphate deposited samples, emphasizing the effect of mineralization on
      osteoblast differentiation. In general ALP activity per cell was found to
      decrease from day 7 to day 14 of incubation. SEM and fluorescence microscopy
      revealed good osteoblast alignment and orientation along the axis of the patterns
      when micropatterned films were used. This study shows that it is possible to
      prepare cell carriers suitable for tissue engineering through choice of
      appropriate surface topography and surface chemistry. Presence of chemical cues
      and micropatterns on the surface enhance cell orientation and bone formation.

PMID- 15576173
TI  - De novo engineering of reticular connective tissue in vivo by silk fibroin
      nonwoven materials.
AB  - Biologically tolerated biomaterials are the focus of intense research. In this
      work, we examined the biocompatibility of three-dimensional (3D) nonwovens of
      sericin-deprived, Bombyx mori silk fibroin (SF) in beta-sheet form implanted into
      the subcutaneous tissue of C57BL6 mice, using sham-operated mice as controls.
      Both groups of mice similarly healed with no residual problem. Macroarray
      analysis showed that an early (day 3) transient expression of macrophage
      migration inhibitory factor (MIF) mRNA, but not of the mRNAs encoding for 22
      additional proinflammatory cytokines, occurred solely at SF-grafted places, where
      no remarkable infiltration of macrophages or lymphocytes subsequently happened.
      Even an enduring moderate increase in total cytokeratins without epidermal
      hyperkeratosis and a transient (days 10-15) upsurge of vimentin occurred
      exclusively at SF-grafted sites, whose content of collagen type-I, after a
      delayed (day 15) rise, ultimately fell considerably under that proper of sham
      operated places. By day 180, the interstices amid and surfaces of the SF chords,
      which had not been appreciably biodegraded, were crammed with a newly produced
      tissue histologically akin to a vascularized reticular connective tissue, while
      some macrophages but no lymphocytic infiltrates or fibrous capsules occurred in
      the adjoining tissues. Therefore, SF nonwovens may be excellent candidates for
      clinical applications since they both enjoy a long-lasting biocompatibility,
      inducing a quite mild foreign body response, but no fibrosis, and efficiently
      guide reticular connective tissue engineering.

PMID- 15576174
TI  - Low-density cultures of bovine chondrocytes: effects of scaffold material and
      culture system.
AB  - Chondrocytes were seeded on either agarose or polyglycolic acid (PGA) unwoven
      meshes at 10 million cells/ml of scaffold volume to evaluate the effect that
      these two biomaterials have on the low-density culture of chondrocytes in a
      rotating-wall bioreactor. For both static and bioreactor culture, agarose
      constructs contained more glycosaminoglycan than their PGA counterparts. However,
      the PGA constructs contained more collagen for both culture conditions when
      compared to agarose. For the low seeding density of this study, PGA constructs
      cultured in the bioreactor did not outperform static cultures when comparing
      collagen content after 8 weeks. The mechanical properties of the PGA constructs
      also did not improve with culture time. Similar results were observed with the
      agarose culture, though both static- and bioreactor-culture agarose constructs
      exhibited increases in aggregate modulus at the end of the culture period. As in
      PGA culture, chondrocytes cultured in agarose may require a higher density to
      reap the benefits of the bioreactor environment.

PMID- 15576175
TI  - The resistance of polyvinylpyrrolidone-iodine-poly(-caprolactone) blends to
      adherence of Escherichia coli.
AB  - In this study, the resistance of biodegradable biomaterials, composed of blends
      of poly(-caprolactone) (PCL) and the polymeric antimicrobial complex,
      polyvinylpyrrolidone-iodine (PVP-I) to the adherence of a clinical isolate of
      Escherichia coli is described. Blends of PCL composed of a range of high (50,000
      g mol(-1)) to low (5000 g mol(-1)) molecular weight ratios of polymer and either
      devoid of or containing PVP-I (1% w/w) were prepared by solvent evaporation.
      Following incubation (4 h), there was no relationship between m. wt. ratio of PCL
      in films devoid of PVP-I and adherence of E. coli. Conversely, microbial
      adherence to PCL containing PVP-I decreased as the ratio of high:low m. wt.
      polymer was decreased and was approximately 1000 fold lower than that to
      comparator films devoid of PVP-I. Following periods of immersion of PVP-I
      containing PCL films under sink conditions in phosphate buffered saline,
      subsequent adherence of E. coli was substantially reduced for 2 days (40:60 m.
      wt. ratio) and 6 days (100:0 m. wt. ratio). Concurrent exposure of PCL and E.
      coli to sub-minimum inhibitory concentrations (sub-MIC) of PVP-I significantly
      reduced microbial adherence to the biomaterial; however, the molecular weight
      ratio of PCL did not affect this outcome. Pretreatment of PCL with similar sub
      MIC of PVP-I prior to inclusion within the microbial adherence assay
      significantly decreased the subsequent adherence of E. coli. Greatest reduction
      in adherence was observed following treatment of PCL (40:60 m. wt. ratio) with
      0.0156% w/w PVP-I. In conclusion, this study has illustrated the utility of PVP-I
      as a suitable therapeutic agent for incorporation within PCL as a novel
      biomaterial. Due to the combined antimicrobial and biodegradable properties,
      these biomaterials offer a promising strategy for the reduction in medical device
      related infection.

PMID- 15576176
TI  - Long term assessment of axonal regeneration through polyimide regenerative
      electrodes to interface the peripheral nerve.
AB  - Polyimide sieve electrodes were implanted between the severed ends of the sciatic
      nerve in rats. The degree of axonal regeneration through the electrode was
      examined by physiological and histological methods from 2 to 12 months
      postimplantation. Regeneration was successful in the 30 animals implanted.
      Functional reinnervation of hindlimb targets progressed to reach maximal levels
      at 6 months. Comparatively, the reinnervation of distal plantar muscles was lower
      than that of proximal muscles and of digital nerves. The number of regenerated
      myelinated fibers increased from 2 to 6 months, when it was similar to control
      values. The majority of myelinated fibers crossing the via holes and regenerated
      through the distal nerve had a normal appearance. However, in a few cases decline
      of target reinnervation and loss of regenerated nerve fibers was found from 6 to
      12 months postimplantation. Motor axons labeled by ChAT immunoreactivity
      regenerated scattered within minifascicles, although they were found at higher
      density at the periphery of the regenerated nerve. The number of ChAT-positive
      axons was markedly lower distally than proximally to the sieve electrode.

PMID- 15576177
TI  - Effective use of optimized, high-dose (50 kGy) gamma irradiation for pathogen
      inactivation of human bone allografts.
AB  - The safety of tissue allografts has come under increased scrutiny due to recent
      reports of allograft-associated bacterial and viral infections in tissue
      recipients. We report that 50 kGy of gamma irradiation, nearly three times the
      dose currently used, is an effective pathogen inactivation method when used under
      optimized conditions that minimize damage to the tissue. Cancellous bone dowels
      treated with a radioprotectant solution and 50 kGy of optimized irradiation had
      an ultimate compressive strength and modulus of elasticity equal to
      conventionally irradiated (18 kGy) and non-irradiated control bone grafts. We
      subjected bone dowels treated with this pathogen inactivation method to an in
      vitro cytotoxicity test using three different mammalian cell lines and concluded
      that the treated grafts were not cytotoxic. The log reduction of nine pathogens
      spiked into radioprotectant-treated bone irradiated to 50 kGy was also tested. We
      achieved 4.9 logs of inactivation of a model virus for HIV and hepatitis C and 5
      logs inactivation of a model virus for human parvovirus B-19. Complete
      inactivation (6.0-9.2 logs) of seven clinically relevant microorganisms was
      demonstrated. The results show that a combination of radioprotectants and
      optimized, high-dose gamma irradiation is a viable method for producing safer
      cancellous bone grafts that have the mechanical strength of existing grafts.

PMID- 15576178
TI  - Characterisation of resin-dentine interfaces by compressive cyclic loading.
AB  - The aims of this in vitro study were to evaluate the ultra-morphological changes
      in resin-dentine interfaces after different amounts of thermomechanical load
      (TML), and to determine the corresponding microtensile bond strengths (microTBS).
      Enamel/dentine discs with a thickness of 2 mm were cut from 24 human third molars
      and bonded with four adhesives involving different adhesion approaches: Syntac
      (Ivoclar Vivadent; used as multi-step etch-and-rinse adhesive), Clearfil SE Bond
      (Kuraray; two-step self-etch adhesive), Xeno III (Dentsply DeTrey; mixed all-in
      one self-etch primer adhesive system), and iBond (Heraeus Kulzer; non-mixed all
      in-one self-etch adhesive). The resin-dentine discs were cut into beams (width 2
      mm; 2 mm dentine, 2 mm resin composite) and subsequently subjected to cyclic TML
      using ascending amounts of mechanical/thermal cycles (20 N at 0.5 Hz of
      mechanical load and 5-55 degrees C of thermal cycles: for 0/0, 100/3, 1,000/25,
      10,000/250, 100,000/2,500 cycles). Loaded specimens were either cut
      perpendicularly in order to measure microTBS (n=20; crosshead speed: 1 mm/min) or
      were immersed in an aqueous tracer solution consisting of 50 wt% ammoniacal
      silver nitrate and processed for ultra-morphological nanoleakage examination
      using transmission electron microscopy (TEM). microTBS were significantly
      decreased by increasing amounts of TML for all adhesives (p<0.05). Bond strengths
      after 0 vs. 100,000 thermomechanical cycles were: Syntac: 41.3/30.1 MPa; Clearfil
      SE Bond 44.8/32.5 MPa; Xeno III 27.5/13.7 MPa; iBond 27.0/6.2 MPa. Relatively
      early, a certain amount of nanoleakage was observed in all groups by TEM, which
      was more pronounced for Xeno III and iBond. The incidence of nanoleakage remained
      stable or was even reduced with increasing load cycles for all adhesives except
      iBond, where exact failure origins were detected within the adhesive and at the
      top of the hybrid layer.

PMID- 15576179
TI  - Failure analysis of explanted sternal wires.
AB  - To classify and understand the mechanisms of surface damages and fracture
      mechanisms of sternal wires, explanted stainless steel sternal wires were
      collected from patients with sternal dehiscence following open-heart surgery.
      Surface alterations and fractured ends of sternal wires were examined and
      analyzed. Eighty fractured wires extracted from 25 patients from January 1999 to
      December 2003, with mean implantation interval of 55+/-149 days (range 5-729
      days) after cardiac surgery, were studied by various techniques. The extracted
      wires were cleaned and the fibrotic tissues were removed. Irregularities and
      fractured ends were assayed by a scanning electron microscopy. After
      stereomicroscopy and documentation, the explants were cleaned with 1% sodium
      hypochlorite to remove the blood and tissues and was followed by cleaned with
      deionized water and alcohol. The explants were examined by stereomicroscopy, and
      irregularities on surface and fracture surfaces of sternal wires were assayed by
      scanning electron microscopy, energy dispersive X-ray analysis (EDAX) and X-ray
      mapping. The explants with surrounding fibrotic tissue were stained and examined
      with stereomicroscopy and transmission electronic microscopy. Corrosion pits were
      found on the surface of explanted sternal wires. EDAX and X-ray mapping
      examinations revealed diminution of nickel concentration in the severely corroded
      pits on sternal wires. A feature of transgranular cracking was observed for
      stress corrosion cracking and striation character for typical corrosion fatigue
      was also identified. TEM examination of tissue showed the metallic particles in
      phagolysosomes of macrophages inside the surrounding sternal tissue. The synergic
      effect of hostile environment and the stress could be the precursors of failures
      for sternal wires.

PMID- 15576180
TI  - Epithelial internalization of superparamagnetic nanoparticles and response to
      external magnetic field.
AB  - Superparamagnetic magnetite nanoparticles (MNP) coated with silica were
      synthesized and chronically implanted into the middle ear epithelial tissues of a
      guinea pig model (n=16) for the generation of force by an external magnetic
      field. In vivo limitations of biocompatibility include particle morphology, size
      distribution, composition and mode of internalization. Synthesis of MNP was
      performed using a modified precipitation technique and they were characterized by
      transmission electron microscopy, X-ray diffractometry and energy dispersive
      spectroscopy, which verified size distribution, composition and silica
      encapsulation. The mechanism for internalizing 16+/-2.3 nm diameter MNP was
      likely endocytosis, enhanced by magnetically force. Using sterile technique,
      middle ear epithelia of tympanic membrane or ossicles was exposed and a
      suspension of particles with fluoroscein isothiocyanate (FITC) label applied to
      the surface. A rare earth, NdFeBo magnet (0.35 T) placed under the animal, was
      used to pull the MNP into the tissue. After 8 days, following euthanasia, tissues
      were harvested and confocal scanning laser interferometry was used to verify
      intracellular MNP. Displacements of the osscicular chain in response to an
      external sinusoidal electromagnetic field were also measured using laser Doppler
      interferometry. We showed for the first time a physiologically relevant,
      biomechanical function, produced by MNP responding to a magnetic field.

PMID- 15576181
TI  - Novel biomaterials for bisphosphonate delivery.
AB  - One type of gem-bisphosphonate (Zoledronate) has been chemically associated onto
      calcium phosphate (CaP) compounds of various compositions. For that purpose, CaP
      powders of controlled granulometry have been suspended in aqueous Zoledronate
      solutions of variable concentrations. Using mainly (31)P NMR spectroscopy, two
      different association modes have been observed, according to the nature of the
      CaP support and/or the initial concentration of the Zoledronate solution. beta
      tricalcium phosphate (beta-TCP) and mixtures of hydroxyapatite and beta-TCP
      (BCPs) appear to promote Zoledronate-containing crystals formation. On the other
      hand, at concentrations <0.05 mol l(-1) CDAs (calcium deficients apatites) seem
      to undergo chemisorption of the drug through a surface adsorption process, due to
      PO(3) for PO(4) exchange, that is well described by Freundlich equations. At
      concentrations >0.05 mol l(-1), crystalline needles of a Zoledronate complex form
      onto the CDAs surface. The ability of such materials to release Zoledronate,
      resulting in the inhibition of osteoclastic activity, was shown using a specific
      in vitro bone resorption model.

PMID- 15576182
TI  - Silver ion release from antimicrobial polyamide/silver composites.
AB  - Silver ion (Ag(+)) the versatile antimicrobial species was released in a steady
      and prolonged manner from a silver-filled polyamide composite system. Metallic
      silver powder having varying specific surface area (SSA) has been used as a
      resource of biocide in polyamide. Strong evidences are found showing the release
      of the antimicrobial species from the resulting composite upon soaking it in
      water due to the interaction of the diffused water molecules with the dispersed
      silver powder within the matrix. The Ag(+) release was observed as increasing
      with time and concentration of the silver powder and is found to be influenced by
      the SSA of the silver powder, changes in the physical state of the composite
      specimen as a result of the water diffusion and the composite morphology. It is
      observed that the Ag(+) release increases initially which is followed by a
      marginal increase between day 4 and 6. Composites containing higher amounts of
      silver (4 and 8 wt%) exhibit a further rise in Ag(+) release from the sixth day
      of storage in water. Composite containing silver particles with the lowest
      specific surface area (0.78 m(2)/g) showed highest Ag(+) release. SEM shows a
      finer dispersion of the silver powder (4 wt%) having lowest SSA. However
      particles with higher (1.16 and 2.5 m(2)/g) SSA possess an agglomerated
      morphology leading to lower Ag(+) release. The composites are found to release
      Ag(+) at a concentration level capable of rendering an antimicrobial efficacy.

PMID- 15576183
TI  - Synthesis and drug release behavior of poly (trimethylene carbonate)-poly
      (ethylene glycol)-poly (trimethylene carbonate) nanoparticles.
AB  - ABA-type triblock copolymers poly (trimethylene carbonate)-poly (ethylene glycol)
      poly (trimethylene carbonate) were synthesized by ring-opening polymerization of
      trimethylene carbonate initiated by dihydroxyl poly (ethylene glycol). The
      critical micelle concentration of amphiphilic triblock copolymers in aqueous
      solution was determined by fluorescence spectroscopy using 9-chloromethyl
      anthracene as fluorescence probe. Core-shell-type nanoparticles were prepared by
      the dialysis technique. Transmission electron microscopy images showed that these
      nanoparticles were regularly spherical in shape. Micelle size determined by
      dynamic light scattering is 50-160 nm. Anticancer drug methotrexate (MTX) as
      model drug was loaded in the polymeric nanoparticles. X-ray powder diffraction
      spectra showed that model drugs were molecularly dispersed in the core. In vitro
      release behavior of MTX was investigated.

PMID- 15576184
TI  - Efficacy of antibiotics-loaded interpenetrating network (IPNs) hydrogel based on
      poly(acrylic acid) and gelatin for treatment of experimental osteomyelitis: in
      vivo study.
AB  - The safety and efficacy of gentamycin sulphate (GS)- or vancomycin hydrochloride
      (VCl)-loaded polymer devices based on poly(acrylic acid) and gelatin crosslinked
      selectively using 0.3 mol % N,N'-methylene bisacrylamide and 1 wt% glutaraldehyde
      were evaluated by varying the drug concentration onto the devices. The placebo
      and drug-loaded device of AxGx (acrylic acid:gelatin: 1:1 w/w) were employed for
      the treatment of experimental osteomyelitis in rabbit. Rabbits were categorized
      into four groups. Twelve rabbits in each group were treated with 12+/-1 mg of
      AxGx-1a (22% w/w GS), 12+/-1 mg of AxGx-1b (44% w/w GS), 16+/-1 mg of AxGx-1b
      (44% w/w GS) and 16+/-1 mg of AxGx-1c (44% w/w VCl). The drug concentration was
      measured following implantation in the adjacent tissue of femoral cavity, and
      serum. In femoral cavity maximum drug concentration was found on the 7th day with
      all the four types of devices. No drug was found after 21 days, at the local site
      with devices AxGx-1a and AxGx-1b (12+/-1 mg), whereas it was detected after 6
      weeks with 16+/-1 mg device (44% w/w GS or VCl). Macroscopic evaluation after
      treatment revealed that swelling, redness, local warmth and drainage decreased
      depending upon the drug loading of the implants. Sequential radiographs,
      histology, microbiologic assay and scanning electron micrography demonstrated
      devices AxGx-1b and AxGx-1c (16+/-1 mg of 44% w/w drug loading) to be the most
      suitable device, which heals the infection after 6 weeks of treatment. No
      significant difference (p>0.05) in the rate of healing was observed between GS-
      and VCl-loaded devices. None of the implant showed toxic level of drug in serum
      at any given time.

PMID- 15576185
TI  - Physically crosslinked alginate/N,O-carboxymethyl chitosan hydrogels with calcium
      for oral delivery of protein drugs.
AB  - In the study, a complex composed of alginate blended with a water-soluble
      chitosan (N,O-carboxymethyl chitosan, NOCC) was prepared to form
      microencapsulated beads by dropping aqueous alginate-NOCC into a Ca(2+) solution.
      These microencapsulated beads were evaluated as a pH-sensitive system for
      delivery of a model protein drug (bovine serum albumin, BSA). The main advantage
      of this system is that all procedures used were performed in aqueous medium at
      neutral environment, which may preserve the bioactivity of protein drugs. The
      swelling characteristics of these hydrogel beads at distinct compositions as a
      function of pH values were investigated. It was found that the test beads with an
      alginate-to-NOCC weight ratio of 1:1 had a better swelling characteristic among
      all studied groups. With increasing the total concentration of alginate-NOCC, the
      effective crosslinking density of test beads increased significantly and a
      greater amount of drug was entrapped in the polymer chains (up to 77%). The
      swelling ratios of all test groups were approximately the same ( approximately
      3.0) at pH 1.2. At pH 7.4, with increasing the total concentration of alginate
      NOCC, the swelling ratios of test beads increased significantly (20.0-40.0), due
      to a larger swelling force created by the electrostatic repulsion between the
      ionized acid groups (-COO(-)). It was shown that BSA was uniformly distributed in
      all test beads. At pH 1.2, retention of BSA in hydrogels may be improved by
      rinsing test beads with acetone (the amount of BSA released was below 15%). At pH
      7.4, the amounts of BSA released increased significantly ( approximately 80%) as
      compared to those released at pH 1.2. With increasing the total concentration of
      alginate-NOCC, the release of encapsulated proteins was slower. Thus, the calcium
      alginate-NOCC beads with distinct total concentrations developed in the study may
      be used as a potential system for oral delivery of protein drugs to different
      regions of the intestinal tract.

PMID- 15576186
TI  - A novel non-toxic camptothecin formulation for cancer chemotherapy.
AB  - The use of a novel injectable biocompatible and biodegradable camptothecin
      polymer implant for sustained intra-tumoral release of high concentrations of
      camptothecin is described. The drug delivery vehicle is an in situ thermogelling
      formulation, which is based on the natural biopolymer chitosan. This formulation,
      containing homogeneously dispersed camptothecin, was implanted intra-tumorally
      into a sub-cutaneous mouse tumor model (RIF-l). The effectiveness of treatment
      was measured in terms of tumor growth delay (TGD). Animals treated with the
      polymer implants containing camptothecin had significantly longer TGDs compared
      to untreated animals as well as to animals treated systemically with camptothecin
      by intra-peritoneal injection with no evidence of toxicity in terms of loss of
      body weight. The results indicate that this novel biodegradable polymer implant
      is an effective vehicle for the sustained intra-tumoral delivery of camptothecin
      which might also be suitable to deliver other insoluble anti-cancer drugs such as
      taxol.

PMID- 15576187
TI  - Synthesis and characterization of the paclitaxel/MPEG-PLA block copolymer
      conjugate.
AB  - A paclitaxel/MPEG-PLA block copolymer conjugate was prepared in three steps: (1)
      hydroxyl-terminated diblock copolymer of monomethoxy-poly(ethylene glycol)-b
      poly(lactide) (MPEG-PLA) was synthesized by ring-opening polymerization of L
      lactide using MPEG as a maroinitiator; (2) it was converted to carboxyl
      terminated MPEG-PLA by reacting with mono-t-butyl ester of diglycolic acid and
      subsequent deprotecting the t-butyl group with TFA; (3) the latter was reacted
      with paclitaxel in the presence of dicyclohexylcarbodiimide and
      dimethylaminopyridine. Structures of the polymers synthesized were confirmed by
      (1)H NMR, and their molecular weights were determined by gel permeation
      chromatography. The antitumor activity of the conjugate against human liver
      cancer H7402 cells was evaluated by MTT method. The results showed that
      paclitaxel can be released from the conjugate without losing cytotoxicity.

PMID- 15576188
TI  - Self-gelling hydrogels based on oppositely charged dextran microspheres.
AB  - This paper presents a novel self-gelling hydrogel potentially suitable for
      controlled drug delivery and tissue engineering. The macroscopic gels are
      obtained by mixing dispersions of oppositely charged crosslinked dextran
      microspheres. These microspheres in turn were prepared by crosslinking of dextran
      derivatized with hydroxyethyl methacrylate emulsified in an aqueous poly(ethylene
      glycol) solution. Negatively or positively charged microspheres were obtained by
      addition of methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA) to
      the polymerization mixture. Rheological analysis showed that instantaneous
      gelation occurred when equal volumes of oppositely charged microspheres,
      dispersed in buffer solutions of pH 7, were mixed. The shear modulus of the
      networks could be tailored from 30 to 6500 Pa by varying the water content of the
      system. Moreover, controlled strain and creep experiments showed that the formed
      networks were mainly elastic. Importantly for application of these systems, e.g.
      as controlled matrix of pharmaceutically active proteins, it was demonstrated
      that the hydrogel system has a reversible yield point, meaning that above a
      certain applied stress, the system starts to flow, whereas when the stress is
      removed, gel formation occurred. Further it was shown that the network structure
      could be broken by either a low pH or a high ionic strength of the medium. This
      demonstrates that the networks, formed at pH 7 and at low ionic strength, are
      held together by ionic interactions between the oppositely charged dextran
      microspheres. This system holds promise as injectable gels that are suitable for
      drug delivery and tissue engineering applications.

PMID- 15576189
TI  - Size and temperature effects on poly(lactic-co-glycolic acid) degradation and
      microreservoir device performance.
AB  - The component materials of controlled-release drug delivery systems are often
      selected based on their degradation rates. The release time of a drug from a
      system will strongly depend on the degradation rates of the component polymers.
      We have observed that some poly(lactic-co-glycolic acid) polymers (PLGA) exhibit
      degradation rates that depend on the size of the polymer object and the
      temperature of the surrounding environment. In vitro degradation studies of four
      different PLGA polymers showed that 150 microm thick membranes degraded more
      rapidly than 50 microm thick membranes, as characterized by gel permeation
      chromatography and mass loss measurements. Faster degradation was observed at 37
      degrees C than 25 degrees C, and when the saline media was not refreshed. A
      biodegradable polymeric microreservoir device that we have developed relies on
      the degradation of polymeric membranes to deliver pulses of molecules from
      reservoirs on the device. Earlier molecular release was seen from devices having
      thicker PLGA membranes. Comparison of an in vitro release study from these
      devices with the degradation study suggests that reservoir membranes rupture and
      drug release occurs when a membrane threshold molecular weight of 5000-15000 is
      reached.

PMID- 15576190
TI  - The use of chitosan as a condensing agent to enhance emulsion-mediated gene
      transfer.
AB  - Previously we have formulated a new cationic emulsion, composed of 3beta [N
      (N',N'-dimethylaminoethane) carbamoyl] cholesterol and dioleoylphosphatidyl
      ethanolamine, castor oil and Tween 80, and it efficiently delivered plasmid DNA
      into various cancer cells with low toxicity. Chitosan is a natural cationic
      polysaccharide and is able to form polyelectrolyte complexes with DNA, in which
      the DNA is condensed and protected against nuclease degradation. Based on these
      facts, chitosan was used as a condensing agent to enhance the transfection
      efficiency of cationic emulsion-mediated gene delivery vehicle. The particle
      size, zeta potential and transmission electron micrographs of DNA/emulsion
      complexes were observed before and after condensation by chitosan. In vitro
      transfection efficiency of naked or precondensed DNA/emulsion (pcDNA/E) complexes
      was investigated in human hepatoma cells (HepG2) using flow cytometer, confocal
      microscope and western blot. In addition, in vivo gene transfer was also
      evaluated as GFP mRNA expression by reverse transcriptase-polymerase chain
      reaction. The size of transfection complexes was reduced after the condensation
      of DNA by chitosan. Moreover, when the pcDNA/E complexes were administered into
      the mice, the GFP mRNA expression was prolonged in liver and lung until day 6.
      These results suggest that the use of chitosan enhance the in vitro transfection
      efficiency and extend in vivo gene transfer.

PMID- 15576191
TI  - DNA encapsulated magnesium and manganous phosphate nanoparticles: potential non
      viral vectors for gene delivery.
AB  - Nanoparticles of Mg and Mn (II) phosphates encapsulating pDNA were prepared. The
      sizes of these DNA loaded particles in aqueous dispersion were about 100-130 nm
      diameter, and they aggregated with the progression of time. Although magnesium
      phosphate nanoparticles were crystalline, the manganous phosphate nanoparticles
      were found to be amorphous in nature. Nanoparticle dissolution and pDNA release
      were studied using atomic absorption spectroscopy and gel electrophoresis
      experiments. These inorganic phosphate nanoparticles dissolved in mild acidic pH
      ( approximately 5) releasing pDNA indicating that DNA release in the endosomal
      compartment is possible. In vitro transfection in HeLa cells demonstrated that
      while magnesium phosphate nanoparticles showed 100% efficiency, manganous
      phosphate nanoparticles exhibited about 85% transfection efficiency compared to
      that of 'polyfect', as control.

PMID- 15576192
TI  - Multi-channel 3-D cell culture device integrated on a silicon chip for anticancer
      drug sensitivity test.
AB  - A novel three-dimensional cell culture system was constructed with an array of
      cell panels (4 x 5) in a silicon chip, together with multi-channel drug
      containers. Human breast cancer (MCF-7) cells were embedded in a collagen-gel
      matrix and entrapped in a pyramidal-shaped silicon hole. Each cell panel can be
      isolated by a channel composed of a microfluid part and a reservoir. A cell panel
      was exposed to 200 mm KCN for 2 days to demonstrate that each cell panel could be
      independently evaluated under various stimulation conditions. Based on the
      cellular respiration activity, the proliferation behavior was continuously
      monitored on the silicon-based cell array for 5 days using scanning
      electrochemical microscopy (SECM). The cells entrapped in the device (3-D
      culture) proliferated normally, and the proliferation rate was lower than that of
      cells grown in a monolayer cell culture (2-D culture). The effects of three
      anticancer drugs measured simultaneously on the cell chip were in good agreement
      with those obtained by a conventional colorimetric assay. Our results suggest
      that the silicon-based device for 3D culture is appropriate for a
      chemosensitivity assay involving multi-chemical stimulation.

PMID- 15576193
TI  - The enhancement of recombinant protein production by polymer nanospheres in cell
      suspension culture.
AB  - Recombinant Chinese hamster ovary (rCHO) cells are being increasingly used in
      industry for the production of recombinant therapeutic proteins. Three
      dimensional suspension culture is preferred to two-dimensional monolayer culture
      for the efficient large-scale culture of rCHO cells and subsequent mass
      production of recombinant proteins. Previously, we have demonstrated that the use
      of plain polymer nanospheres enhances the growth of anchorage-dependent animal
      cells (human embryonic kidney 293 cells) in suspension culture in serum
      containing medium. Vitronectin and fibronectin were adsorbed onto poly(lactic-co
      glycolic acid) (PLGA) nanospheres (696 nm in average diameter) by immersing the
      nanospheres in fetal bovine serum. In this study, we investigated if the use of
      vitronectin/fibronectin-adsorbed polymer nanospheres enhances recombinant protein
      production in rCHO cell suspension culture in serum-free medium. Cell aggregate
      formation may be critical for the survival and growth of anchorage-dependent
      animal cells in suspension culture, and cells in single cell suspension may
      result in cell death. The addition of vitronectin/fibronectin-adsorbed
      nanospheres to rCHO cell suspension culture promoted the rate and efficiency of
      cell aggregate formation. The nanospheres enhanced cell growth (2.9 folds on day
      10) and, importantly, recombinant antibody production (1.8 folds on day 14),
      compared to suspension culture without nanospheres. The viability of cells in the
      aggregates in the nanosphere-added culture was high for the entire culture period
      of 14 days. Apoptotic activity of cells was much lower in the nanosphere-added
      culture than in the culture without nanospheres on day 5. The nanosphere
      suspension culture method developed in this study may be useful for the mass
      production of recombinant proteins through large-scale suspension culture of
      anchorage-dependent animal cells.

PMID- 15576194
TI  - Aspects of in vitro fatigue in human cortical bone: time and cycle dependent
      crack growth.
AB  - Although fatigue damage in bone induced by cyclic loading has been recognized as
      a problem of clinical significance, few fracture mechanics based studies have
      investigated how incipient cracks grow by fatigue in this material. In the
      present study, in vitro cyclic fatigue experiments were performed in order to
      quantify fatigue-crack growth behavior in human cortical bone. Crack-growth rates
      spanning five orders of magnitude were obtained for the extension of macroscopic
      cracks in the proximal-distal direction; growth-rate data could be well
      characterized by the linear-elastic stress-intensity range, using a simple
      (Paris) power law with exponents ranging from 4.4 to 9.5. Mechanistically, to
      discern whether such behavior results from "true" cyclic fatigue damage or is
      simply associated with a succession of quasi-static fracture events, cyclic crack
      growth rates were compared to those measured under sustained (non-cyclic)
      loading. Measured fatigue-crack growth rates were found to exceed those
      "predicted" from the sustained load data at low growth rates ( approximately 3 x
      10(-10) to 5 x 10(-7) m/cycle), suggesting that a "true" cyclic fatigue
      mechanism, such as alternating blunting and re-sharpening of the crack tip, is
      active in bone. Conversely, at higher growth rates ( approximately 5 x 10(-7) to
      3 x 10(-5) m/cycle), the crack-growth data under sustained loads integrated over
      the loading cycle reasonably predicts the cyclic fatigue data, indicating that
      quasi-static fracture mechanisms predominate. The results are discussed in light
      of the occurrence of fatigue-related stress fractures in cortical bone.

PMID- 15576195
TI  - Immunological approaches against nosocomial infections. Proceedings of an
      international workshop. Veyrier-du-Lac, France, 19-21 November 2003.

PMID- 15576196
TI  - Transcriptome analysis of quorum-sensing regulation and virulence factor
      expression in Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa possesses two well-studied
      quorum-sensing (QS) systems (las and rhl) that are important in the production of
      virulence factors, antibiotic sensitivity, and biofilm development. High-density
      oligonucleotide microarrays were used to further characterize the las QS system
      and to investigate the effect of environment (planktonic or biofilm mode of
      growth, absence or presence of oxygen) and nutritional conditions on detection of
      transcripts encoding QS-regulated virulence factors. Transcriptome results
      indicate that the QS system is far more complex than previously proposed.
      Interestingly, we found that many QS-regulated genes encoding virulence products
      were expressed in all conditions investigated.

PMID- 15576197
TI  - Host cell-pathogen interface: molecular mechanisms and genetics.
AB  - Host factors determining the host-pathogen interaction are crucial for the
      reaction pattern leading to the threat of nosocomial infections. A soluble
      protein with the ability to recognize a variety of microorganisms is LPS binding
      protein (LBP). The recently identified family of Toll-like receptors (TLRs)
      represents the major group of cellular signaling receptors for pathogens. The
      discovery of genetic variations of these proteins caused by single nucleotide
      polymorphisms (SNPs) has led to first studies aimed at elucidating a potential
      link between genomic variation of the host and susceptibility to infections. The
      current state of these analyses is summarized here.

PMID- 15576198
TI  - Innate immune responses during infection.
AB  - The innate immune system senses bacteria in the environment and defends against
      infection. Here we will discuss two types of sensor protein families. The plasma
      membrane receptors that comprise the Toll-like receptor (TLRs) family and the
      intracellular proteins termed NOD1 and NOD2. These proteins directly bind
      bacterial products such as lipopolysaccharides (LPS), peptidoglycan fragments,
      bacterial DNA, and receptor binding leads to intracellular signaling and gene
      expression. TLR signaling involves members of the MyD88 family of adaptor
      proteins. In contrast NOD1 or NOD2 utilize pathways that do not depend on the
      MyD88 family members.

PMID- 15576199
TI  - Rationale for the development of immunotherapy regimens against enterococcal
      infections.
AB  - Enterococci are the third most common pathogen isolated in bloodstream
      infections. Increasing resistance against multiple antimicrobial agents has left
      few treatment options for enterococcal infections, and alternative therapeutic
      approaches are needed. Although a variety of virulence factors have been
      described for Enterococcus faecalis, only aggregation substance (AS) and a
      teichoic acid-like capsular polysaccharide have been evaluated for their
      potential for vaccine development. Antibodies raised against purified capsular
      polysaccharide are highly opsonic and protect mice against bacteremia after
      active and passive immunization. Since E. faecalis expresses only a limited
      number of capsular serotypes, this antigen may be an attractive candidate for
      development of a conjugate vaccine.

PMID- 15576200
TI  - A humanized monoclonal antibody targeting Staphylococcus aureus.
AB  - This current presentation describes the in vitro and in vivo characterization of
      Aurexis (tefibazumab), a humanized monoclonal antibody that exhibits a high
      affinity and specificity and for the Staphylococcus aureus MSCRAMM (Microbial
      Surface Components Recognizing Adhesive Matrix Molecules) protein ClfA. Aurexis
      inhibited ClfA binding to human fibrinogen, and enhanced the opsonophagocytic
      uptake of ClfA-coated beads. Preclinical in vivo testing revealed that a single
      administration of Aurexis significantly protected against an IV challenge with a
      methicillin resistant S. aureus (MRSA) strain in murine septicemia and rabbit
      infective endocarditis (IE) models. Safety and pharmacokinetic data from a 19
      patient phase I study support continued evaluation of Aurexis in phase II
      studies.

PMID- 15576201
TI  - Prophylaxis and therapy of Pseudomonas aeruginosa infection in cystic fibrosis
      and immunocompromised patients.
AB  - Pseudomonas aeruginosa is an opportunistic bacterium responsible for chronic lung
      infection in cystic fibrosis patients, as well as nosocomial infections in
      immunocompromised patients. An O-polysaccharide-toxin A conjugate vaccine was
      evaluated for prophylaxis of P. aeruginosa in cystic fibrosis patients.
      Vaccination proved to be useful in preventing and/or delaying infection. Fully
      human monoclonal antibodies (mAb) against P. aeruginosa O-polysaccharides were
      developed for the treatment of immunocompromised patients in whom active
      immunoprophylaxis is not applicable. Characterisation of the mAb revealed high
      antigen specificity and avidity, as well as excellent efficacy in relevant in
      vitro and in vivo systems, permitting future clinical evaluation.

PMID- 15576202
TI  - Rotavirus vaccines and the prevention of hospital-acquired diarrhea in children.
AB  - Rotavirus, the major cause of severe acute dehydrating gastroenteritis in
      children less than 5 years of age, is responsible for an estimated 20-50% of all
      hospitalizations for diarrhea and approximately 440,000 deaths annually,
      primarily in the developing world. Rotavirus vaccines are considered the most
      promising means for disease prevention. While the prime rationale for developing
      rotavirus vaccines has been the enormous burden of rotavirus infection leading to
      severe and fatal disease, a secondary benefit may be the prevention of nosocomial
      rotavirus diarrhea. We have reviewed the burden of intra-hospital-acquired
      rotavirus infections from several countries and found that in the United States
      alone, as many as 25% of rotavirus hospitalizations or approximately 16,000
      18,000 hospitalizations each year might be due to rotavirus infections acquired
      within hospitals. To countries with low rotavirus-associated mortality,
      prevention of these infections and the resulting economic savings therefore
      represent an important secondary goal. Several rotavirus vaccines are in
      development, and two candidates are currently being tested in large-scale safety
      and efficacy trials. Development of safe and effective rotavirus vaccines will
      protect children worldwide against the severe consequences of rotavirus
      infections including prolonged hospitalizations for nosocomially acquired
      infections.

PMID- 15576203
TI  - Genetic characterization of methicillin-resistant Staphylococcus aureus.
AB  - The genome structure of Staphylococcus aureus is analyzed. The genome is composed
      of two domains. The first domain, descendent from an ancestral bacterial species,
      contains house-keeping genes that showed highest homology to those of Bacillus
      species. The second domain contained the genes responsible for virulence and drug
      resistance in human infection that seems to have been acquired from other
      bacterial species via lateral gene transfer. The latter domain constitutes the
      genetic information that makes S. aureus a notorious hospital pathogen.

PMID- 15576204
TI  - Host-pathogen interactions in Streptococcus pyogenes infections, with special
      reference to puerperal fever and a comment on vaccine development.
AB  - Streptococcus pyogenes (group A streptococcus) causes a variety of diseases,
      including acute pharyngitis, impetigo, rheumatic fever and the streptococcal
      toxic shock syndrome. Moreover, S. pyogenes was responsible for the classical
      example of a nosocomial infection, the epidemics of puerperal fever (childbed
      fever) that caused the death of numerous women in earlier centuries. The most
      extensively studied virulence factor of S. pyogenes is the surface M protein,
      which inhibits phagocytosis and shows antigenic variation. Recent data indicate
      that many M proteins confer phagocytosis resistance because the variable N
      terminal region has non-overlapping sites that specifically bind two components
      of the human immune system, the complement inhibitor C4b-binding protein (C4BP)
      and IgA-Fc. Concerning puerperal fever, molecular and epidemiological analysis
      suggests that the S. pyogenes surface protein R28 may have played a pathogenetic
      role in these epidemics. This article summarizes the properties of M protein and
      the R28 protein and considers a potential problem encountered in connection with
      the use of animal models for vaccine development.

PMID- 15576205
TI  - The impact of the impact factor.

PMID- 15576206
TI  - Volunteering in the developing world: The 2003-2004 Sterling Bunnell Traveling
      Fellowship to Honduras and Cambodia.
AB  - One of the goals of my Sterling Bunnell Traveling Fellowship, sponsored by the
      American Society for Surgery of the Hand and the American Foundation for Surgery
      of the Hand, was to serve the poor in developing countries. I had the unique
      opportunities to work in Honduras and Cambodia, 2 countries with rich cultural
      heritage residing at opposite ends of the world. This report describes my
      observations and my experiences in these 2 countries.

PMID- 15576207
TI  - Analysis of anatomic variations in cleft hands.
AB  - PURPOSE: This study presents an overview of the clinical and x-ray findings
      observed in 54 cleft hands of 31 patients. The emphasis was on a detailed
      analysis of typical malformation-associated x-ray patterns such as aplasia and
      synostosis, with findings arranged as a function of cleft location and of the
      Manske and Halikis classification. METHODS: The charts and radiographs of 31
      patients with 54 cleft hands were reviewed retrospectively and compared with data
      reported in the literature. Important clinical and x-ray findings as well as the
      typical morphology of cleft hands were analyzed. Cleft hands were differentiated
      according to their location and according to the Manske and Halikis
      classification. In the different locations the deformities were arranged in
      teratologic sequences. RESULTS: In cleft hands syndactylies were seen in 30 of
      the 54 hands, most commonly between the ring and the small finger. In 3 hands
      polydactylies were noted. Analysis of the x-ray morphology showed 2 typical
      patterns: aplasia and synostoses. Location-specific teratologic sequences showed
      that radial cleft hands were bilateral more frequently and were associated
      significantly more frequently with cleft feet. Aplasias predominated in radial
      cleft hands, whereas synostoses were more common in central cleft hands. In terms
      of the Manske and Halikis classification the unilateral cleft hands often
      corresponded to type I whereas bilateral cleft hands with cleft feet mainly were
      type IV and type V deformities. Cleft hands with synostoses often were seen in
      types I to III whereas cleft hands with aplasias were classified most frequently
      as type V. CONCLUSIONS: Analysis of the patients' clinical data and x-rays showed
      differences between radial and central cleft hands, as well as between the
      different Manske and Halikis types.

PMID- 15576208
TI  - Surgical treatment of type 0 radial longitudinal deficiency.
AB  - PURPOSE: The purpose of this study was 2-fold: (1) to describe the surgical
      anatomy associated with type 0 radial longitudinal deficiency (radially deviated
      hand in the presence of a normal-length radius) and (2) to report the results of
      a surgical procedure designed to improve the alignment of the hand and forearm.
      METHODS: Since 1986 there have been 6 cases of type 0 radial longitudinal
      deficiency in 5 children seen at the St. Louis Shriner's Hospital. These children
      were treated with a surgical procedure to release the radial soft tissues and
      correct the alignment with tendon transfers. Age at surgery ranged from 12 to 40
      months, with an average age of 21 months. The average follow-up period was 21
      months. The tight radial wrist extensors were detached at their distal insertion
      and the tight radial wrist capsule was released dorsally and volarly, thus
      relieving the radial tether. The extensor carpi ulnaris (ECU) tendon also was
      detached just proximal to its insertion and sutured to the dorsal wrist capsule
      to augment wrist extension. The radial wrist extensor tendon was reattached to
      the ECU tendon at its insertion, converting it into an ulnar deviator. RESULTS:
      In each case the radial wrist extensor was noted to be hypoplastic and the radial
      wrist capsule was noted to be tight, tethering the hand in radial deviation. In 4
      cases there was only a single radial wrist extensor tendon. Average radial
      deviation at rest improved from 58 degrees to 12 degrees . Improvement in radial
      deviation at rest averaged 47 degrees , ranging from 25 degrees to 75 degrees .
      Improvement in active wrist extension averaged 53 degrees and improvement in
      passive wrist extension averaged 28 degrees . CONCLUSIONS: For children with type
      0 radial longitudinal deficiency a soft-tissue procedure that releases the radial
      tether and augments ulnar deviation and wrist extension by tendon transfer
      satisfactorily improves wrist alignment with minimal morbidity.

PMID- 15576209
TI  - Surgical treatment of macrodactyly in older children and adults.
AB  - PURPOSE: To introduce a surgical technique for the treatment of macrodactyly in
      older children and adults, to represent the degree of correction obtained by the
      procedure, and to give the functional results. METHODS: Two thumbs and 5 fingers
      of 5 patients aged 12 to 32 years (mean, 17.5 years) with macrodactyly had
      surgery. The amount of tissue sufficient to reconstruct a normal-sized digit was
      left attached with the neurovascular bundle on the concave side of the
      macrodactylic digit and complete excision of whatever remained was performed.
      This requires usually arthrodesis of the distal interphalangeal joint with bone
      shortening. The large skin fold created during bone shortening and remaining
      angulations at the proximal phalanx were corrected during a second procedure. The
      patients were evaluated for 3 to 9 years (mean, 5.4 years) after the surgery. The
      length and circumferences of the involved digits and their opposites were
      measured before surgery and during the last follow-up examination to calculate
      the differences between the involved and the healthy digits, which were
      documented. The degree of reduction was quantified and noted. Two-point
      discrimination tests and active range of motion of the joints were recorded as
      well. RESULTS: For the thumbs an average 37% of circumference and 15% of length
      were reduced and for the fingers an average 44% of circumference and 35% of
      length were reduced. Ranges of motion of the joints of the involved digits were
      the same or nearly the same as before surgery in all of the cases. Two-point
      discriminations at the pulp of the involved digits were found to be the same as
      presurgical values in all digits. CONCLUSIONS: The technique is precise and
      simplifies the planning of the surgery. Although the macrodactylic digits with
      angulation deformities required a subsequent surgery for corrections patients
      with marked macrodactyly of the digit without a very wide proximal phalanx and
      metacarpal gained most from this technique.

PMID- 15576210
TI  - Bilateral hand transplantation: bone healing under immunosuppression with
      tacrolimus, mycophenolate mofetil, and prednisolone.
AB  - PURPOSE: Little is known about bone healing after composite tissue
      transplantation that requires pharmacologic immunosuppression. Bone integration
      and callus development were assessed in bilateral hand transplantation. METHODS:
      In this study the course of callus development and callus maturation were
      assessed by color Doppler sonography and radiography in a double hand transplant
      and compared with forearm replantation. RESULTS: After hand transplantation,
      ingrowth of small vessels at the bone junction was observed at week 3, calcified
      callus became visible at month 4, and bone union was completed at month 11. A
      similar time course of bone integration was observed after replantation. Plating
      offered sufficient stability. A recipient periostal flap is thought to have
      improved blood supply and favored development and induction of callus.
      CONCLUSIONS: Bone healing after hand transplantation under immunosuppression with
      tacrolimus, mycophenolate mofetil, and prednisolone is identical to that after
      forearm replantation.

PMID- 15576211
TI  - Analysis of prognostic factors in ring avulsion injuries.
AB  - PURPOSE: To report 105 cases of ring avulsion injuries, examine the factors
      affecting rate of survival and functional outcome after reconstruction, and
      evaluate whether these data provide enough evidence to support attempts to repair
      these injuries. METHODS: A retrospective cohort study was conducted in 105
      patients with 105 ring avulsion injuries of all grades of severity treated at our
      center between 1977 and 2003. Factors that could affect the outcome included
      personal (gender, age, smoking history, vascular disease, diabetes mellitus,
      alcohol abuse), injury (finger affected, level of skeletal injury, presence of
      tendon and nerve injury, Urbaniak class as modified by Kay et al, presurgery
      time), and surgery features (number of arteries and veins reconstructed primarily
      and with vein grafts). Results were interpreted based on survival and final
      function. Function was measured by the presence of pain, range of motion, and 2
      point discrimination. RESULTS: Of the 86 digits with inadequate circulation, 11
      digits had primary amputation. Reconstruction was attempted in 75 digits.
      Fourteen digits had secondary amputation because of revascularization failure.
      Failure was attributed to artery problems in 5 digits and to vein problems in 5
      digits and was unknown in 4 digits. The overall survival rate was 81%.
      CONCLUSIONS: Cigarette smoking is not associated with higher risk of
      revascularization failure. Reconstruction of 2 or more veins resulted in higher
      survival rates compared with reconstruction of only 1 vein. Level of bone injury
      is not an accurate indication of whether to attempt reconstruction. Primary nerve
      repair does not lead to a good sensory recovery in most digits. Patients who had
      their digits finally amputated had variable periods of hypersensitivity at the
      stump, which prolonged their convalescence time.

PMID- 15576212
TI  - The adipofascial turn-over flap for coverage of the dorsum of the finger: a
      modified surgical technique.
AB  - PURPOSE: The exact distances from the cutaneous dorsal branches of the digital
      artery to the proximal interphalangeal joint have been established in a previous
      anatomic study. The aim of this report is to incorporate these anatomic data into
      the current way of designing the homodigital adipofascial turn-over flap for
      cutaneous coverage of the dorsum of the finger. Our clinical experience with this
      modified surgical technique to this flap is reported. METHODS: The clinical
      series presented here consists of 40 patients with loss of cutaneous coverage at
      the dorsal aspect of the middle and distal phalanges. Based on our anatomic
      findings the flap was designed to include at least 1 dorsal branch in its
      pedicle. RESULTS: The flap survival was excellent and no donor site complications
      were observed. CONCLUSIONS: The adipofascial turn-over arterial flap has appeared
      as an excellent alternative for achieving early coverage of cutaneous wounds at
      the dorsal aspect of middle and distal phalanges of the long fingers. This flap
      can be designed as an arterial flap in a predictable and reliable way based on
      new anatomic data on the vascularization of the dorsum of the finger.

PMID- 15576213
TI  - Arthrodesis of the thumb metacarpophalangeal joint using a cannulated screw and
      threaded washer.
AB  - We describe a technique of arthrodesis of the thumb metacarpophalangeal joint
      that we performed in 26 patients. Indications for surgery were instability (6
      patients), chronic instability with secondary degenerative joint disease (6),
      osteoarthritis (6), inflammatory arthritis (7), and paralytic boutonniere (1).
      The technique uses the cup-and-cone method of decortication and positioning with
      the internal fixation using a 3.0-mm partially threaded cannulated screw and
      threaded washer (Synthes, Paoli, PA). Twenty-five of 26 joints had clinical and
      radiographic fusion. Average time to radiographic fusion for 24 patients (1
      nonunion, 1 patient without x-rays until 4 months) was 10 weeks. Long-term follow
      up evaluation was available for 20 patients and averaged 32 months (range, 21-44
      months). All 20 had stable radiographic fusion with maintenance of the fusion
      angle. There were no infections and no need for hardware removal. Our results
      indicate that this technique for arthrodesis of the thumb metacarpophalangeal
      joint is effective and reliable, is accomplished easily, and has a low incidence
      of complications.

PMID- 15576214
TI  - A simple fixation method for unstable bony mallet finger.
AB  - Closed treatment has provided good results in uncomplicated cases of mallet
      finger; however, surgical fixation is recommended when there is involvement of
      more than one third of the base of the distal phalanx. Various techniques have
      been described for this purpose. The goal of this report is to present a simple
      method of K-wire fixation and show our results with this procedure.

PMID- 15576215
TI  - The effect of percutaneous pin fixation of the interphalangeal joint on the thumb
      tip force produced by the flexor pollicis longus: a cadaver study.
AB  - PURPOSE: Interphalangeal joint stabilization often is performed concomitantly
      with tendon transfers that restore key pinch (lateral pinch) to the paralyzed
      thumb. The goal of this study was to measure the effect of interphalangeal joint
      stabilization via percutaneous pin fixation on the thumb-tip force produced by
      the flexor pollicis longus (FPL). METHODS: We applied 10 N of force to the tendon
      of the FPL in 7 cadaveric specimens and measured the resulting thumb-tip force in
      the intact thumb and after stabilization of the interphalangeal joint. RESULTS:
      The nominal thumb-tip force was approximately 6 times less than the applied force
      and was directed primarily in the thumb's plane of flexion-extension at an
      oblique angle of 44 degrees relative to the palmar direction (the direction that
      is perpendicular to the thumb tip in the plane). Joint stabilization increased
      significantly the nominal force and oriented the force more toward the palmar
      direction (ie, decreased the obliqueness of the force). CONCLUSIONS: After
      paralysis and a tendon transfer to the paralyzed FPL the FPL is often the only
      muscle actuating the thumb. We conclude that the oblique nominal force direction
      is prone to cause the thumb to slip during pinch. Joint stabilization, however,
      has the capacity to reduce the tendency for slippage because it rotates the force
      toward the palmar direction.

PMID- 15576216
TI  - Extensor mechanism slide for the treatment of proximal interphalangeal joint
      extension lag: an anatomic study.
AB  - PURPOSE: We describe a technique for correction of proximal interphalangeal joint
      (PIP) extensor lag secondary to angulation and/or shortening of proximal phalanx
      fractures. METHODS: Proximal phalanx fracture malunions with 2.5 mm of
      shortening, 5.0 mm of shortening, and apex volar angulation of 40 degrees were
      simulated in 15 cadaver fingers, creating PIP extensor lags. The
      metacarpophalangeal (MCP) joint was pinned in neutral. Transection of the ulnar
      and radial sagittal bands, the extensor digitorum communis (EDC) insertion on the
      MCP joint capsule, and the juncturae tendinae then was performed. The PIP
      extensor lag before and after each of the earlier-noted releases was recorded.
      The MCP joint then was freed and MCP hyperextension was recorded. With the MCP
      joint in neutral position the sagittal bands then were reapproximated with
      sutures and MCP extension was measured. RESULTS: The 2.5 mm of axial shortening,
      5.0 mm of axial shortening, and 40 degrees of apex volar angulation fracture
      models produced an average extensor lag of 6.2 degrees , 25.8 degrees , and 42.5
      degrees , respectively. Maximal correction of PIP extensor lag required
      transection of both sagittal bands, EDC insertion on the MCP capsule, and the
      juncturae tendinae with an average residual extensor lag of -0.8 degrees for the
      2.5-mm shortening model, 0.7 degrees for the 5.0-mm shortening model, and 3.2
      degrees for the 40 degrees -angulation model. The MCP joint hyperextension
      increased by 20 degrees to 30 degrees after the releases but decreased to only
      1.8 degrees if the sagittal bands were reapproximated to the EDC tendon at their
      new resting position with the MCP joint in neutral position. CONCLUSIONS: In the
      cadaver model the PIP extensor lag can be improved substantially by transection
      of the sagittal bands, release of the EDC insertion on the MCP capsule,
      transection of the juncturae tendinae, and reapproximation of the sagittal bands
      to the EDC tendon.

PMID- 15576217
TI  - Excision of the trapezium for osteoarthritis of the trapeziometacarpal joint: a
      study of the benefit of ligament reconstruction or tendon interposition.
AB  - PURPOSE: To investigate whether palmaris longus interposition or flexor carpi
      radialis ligament reconstruction and tendon interposition improved the outcome of
      excision of the trapezium for the treatment of painful osteoarthritis of the
      trapeziometacarpal joint. METHODS: 183 thumbs with trapeziometacarpal
      osteoarthritis were randomized for treatment by either simple trapeziectomy,
      trapeziectomy with palmaris longus interposition, or trapeziectomy with ligament
      reconstruction and tendon interposition using 50% of the flexor carpi radialis
      tendon. A K-wire was passed across the trapezial void during each of the 183
      surgeries to hold the base of the thumb metacarpal at the level of the index
      carpometacarpal joint and was retained for 4 weeks in every case. All patients
      wore a thumb splint for 6 weeks. Each patient had subjective and objective
      assessments of thumb pain, stiffness, and strength before surgery and at 3 months
      and 1 year after surgery. RESULTS: The 3 treatment groups were well matched for
      age, dominance, and presence of associated conditions. Complications were
      distributed evenly among the 3 groups and no cases of subluxation/dislocation of
      the pseudarthrosis were observed. Of the 183 thumbs 82% achieved good pain relief
      and 68% regained sufficient strength to allow normal activities of daily living
      at the 1-year follow-up evaluation. Neither of these subjective outcomes nor the
      range of thumb movement was influenced by the type of surgery performed. Thumb
      key-pinch strength improved significantly from 3.5 kg before surgery to 4.6 kg at
      1 year but the improvement in strength was not influenced by the type of surgery
      performed. CONCLUSIONS: The outcomes of these 3 variations of trapeziectomy were
      very similar at 1-year follow-up evaluation. In the short term at least there
      appears to be no benefit to tendon interposition or ligament reconstruction.

PMID- 15576218
TI  - Commentary: Excision of the trapezium.

PMID- 15576219
TI  - Early failures with a spheric interposition arthroplasty of the thumb basal
      joint.
AB  - PURPOSE: The purpose of this study is to report the early results with the
      Orthosphere (Wright Medical Technology Inc, Arlington, TN) spheric
      interpositional arthroplasty. METHODS: Six women and 1 man had Orthosphere
      arthroplasty between 2000 and 2001. The mean age at the time of surgery was 52
      years (range, 24-73 years) and the mean duration of clinical and radiographic
      follow-up evaluation was 33 months (range, 29-44 months). RESULTS: Six of 7
      Orthosphere implants subsided into the trapezium resulting in pain, weakness, and
      stiffness. There was 1 implant dislocation. Five patients have had revision
      surgery to trapezial excision ligament reconstruction and tendon interposition
      arthroplasty. Of the remaining 2 patients 1 is contemplating presently revision
      surgery and the other is experiencing mild residual pain. No patients were
      satisfied completely with their Orthosphere results. CONCLUSIONS: In our
      experience the early outcome of the Orthosphere interpositional arthroplasty has
      been unacceptable. We no longer use the device at our institutions.

PMID- 15576220
TI  - Basal joint arthroplasty and carpal tunnel release through a single incision: an
      in vitro study.
AB  - PURPOSE: Carpal tunnel syndrome coexists with basal joint arthritis in a large
      percentage of patients. These 2 conditions are often treated surgically through
      separate incisions. The purpose of this cadaver study is to show the effect of
      trapeziectomy and transverse carpal ligament release from the scaphoid tubercle
      on carpal canal pressures. This technique may permit both problems to be
      addressed through the same Wagner incision. METHODS: In 4 fresh frozen cadaver
      limbs pressures in the carpal canal were elevated to 30 mm Hg through a
      percutaneously placed balloon. Pressures were measured using an 18-gauge sideport
      needle via a transducer. Trapeziectomy and release of the transverse carpal
      ligament from the scaphoid were performed in succession through a Wagner incision
      with canal pressures measured after each step. RESULTS: Carpal canal pressures
      decreased after trapeziectomy (mean, 7 mm Hg; range, 3-14 mm Hg) but did not
      return to baseline (0 mm Hg) until complete release of the ligament. CONCLUSIONS:
      Decompression of the carpal tunnel can be performed effectively through a Wagner
      incision during basal joint arthroplasty. This cadaver model shows reduction in
      the canal pressures after trapeziectomy and release of the transverse carpal
      ligament. This single-incision approach is attractive because it may decrease
      morbidity compared with a 2-incision approach in patients with concomitant carpal
      tunnel syndrome and basal joint arthritis.

PMID- 15576221
TI  - Thumb metacarpal vascularized bone graft in long-standing scaphoid nonunion--a
      useful graft via dorsal or palmar approach: a cohort study of 24 patients.
AB  - PURPOSE: Long-standing scaphoid nonunion preferentially is treated by using a
      vascularized bone graft because of its superiority in achieving bone healing. In
      the present study nonunion was repaired using a bone graft raised from the thumb
      metacarpal and vascularized by the first dorsal metacarpal artery. METHODS:
      Twenty-four patients with scaphoid nonunion for longer than 5 years, without
      ligament injuries and panarthrosis, had surgery. According to the location of the
      nonunion and presence of dorsal intercalated segment instability deformity,
      surgery was performed by either a dorsal or palmar approach. The patients had a
      final clinical and radiographic evaluation 12 months after surgery. RESULTS:
      Complete healing was shown in 21 patients but incomplete healing was observed in
      the remaining 3 patients. After surgery patients had marked pain relief, with an
      improved range of motion and grasping strength. Anatomic restoration of carpal
      angles and scaphoid length was observed. None of the patients required additional
      surgery. Before surgery 15 patients presented radiographic signs of wrist
      arthrosis. During surgery, however, cartilage erosion on the proximal pole or on
      the radius articular surface was not confirmed. Despite the presence of
      radiographic arthrosis, wrist symptoms, motion, and grasping strength improved
      after surgery. CONCLUSIONS: Long-standing scaphoid nonunion, even in the presence
      of limited arthrosis, can be treated with surgery and healing promoted by a
      vascularized bone graft. Because of its versatility for use by dorsal or palmar
      approach and reliability, the first dorsal metacarpal artery vascularized bone
      graft represents our method of choice.

PMID- 15576222
TI  - Osteonecrosis of the trapezium treated with a vascularized distal radius bone
      graft.
AB  - A 20-year-old man presented with early stage osteonecrosis of the trapezium,
      diagnosed by magnetic resonance imaging. A vascularized distal radius bone graft
      was performed, with good clinical and radiologic results over a 1-year follow-up
      period. The authors believe that a vascularized distal radius bone graft is an
      ideal treatment for early stage carpal bone necrosis.

PMID- 15576223
TI  - Isolated scaphoid dislocation associated with axial carpal dissociation: an
      unusual injury report.
AB  - We present a report of a patient with an isolated scaphoid dislocation associated
      with a hyperextension and axial loading injury of the carpus required a careful
      and extensive clinical and radiographic evaluation leading to surgical
      intervention to reduce and stabilize the scaphoid and to reduce and hold
      internally the axial carpal injury. Knowledge of the anatomy and the potential
      injury patterns of the carpus will aid the hand surgeon with injury recognition
      and proper treatment.

PMID- 15576224
TI  - Changes in radiocarpal loading characteristics after proximal row carpectomy.
AB  - PURPOSE: To document the changes in wrist loading that occur after proximal row
      carpectomy in a cadaver model. METHODS: The normal radioulnar carpal pressure
      distributions of 7 cadaver wrists were measured using super-low-pressure
      sensitive film. Proximal row carpectomies were performed and the loading
      characteristics re-evaluated. RESULTS: In the lunate fossa the contact area
      increased 37%, the average contact pressure increased 57%, and the location of
      the contact moved radially 5.5 mm. With wrist motion between 40 degrees of
      extension and 20 degrees of flexion the volar/dorsal excursion of the lunate
      fossa contact point increased by 108%. CONCLUSIONS: Significant changes in
      radiocarpal loading occur after proximal row carpectomy. The increased
      radiocarpal excursion with wrist motion may explain the low incidence of
      radiocapitate arthritis in patients who have had proximal row carpectomy.

PMID- 15576225
TI  - Stability of the distal radioulnar joint contributed by the joint capsule.
AB  - PURPOSE: The distal radioulnar joint (DRUJ) capsule is assumed to be an important
      stabilizer of the DRUJ. There are few published data regarding the capsule and
      its specific contribution to stability of the DRUJ. METHODS: We analyzed the
      contribution of the joint capsule to DRUJ stability in a biomechanical study
      consisting of collection of force/displacement data from 16 adult human cadaveric
      upper extremities. Each specimen was subjected to anteroposterior translation
      testing of the radius relative to the ulna in 3 positions of forearm rotation
      (neutral, 60 degrees pronation, 60 degrees supination) by serial sectioning of
      the DRUJ capsule. The experimental conditions tested included intact capsule,
      sectioned dorsal capsule, sectioned volar capsule, and repaired capsule. RESULTS:
      Isolated dorsal capsule sectioning resulted in volar instability of the radius to
      the ulna primarily in the maximum pronated position. Significant dorsal
      instability of the radius was observed after isolated volar capsule sectioning in
      the maximum supinated position. The restabilizing effect of capsule shortening
      was observed near the maximums of forearm rotation. The additional stability
      owing to capsule shortening surpassed that of the distal radioulnar ligament at
      these positions. CONCLUSIONS: We showed the effect of capsular injury on DRUJ
      joint stability and the restabilizing effect of capsule shortening. The
      importance of the capsule to DRUJ stability should be considered when planning
      surgical procedures to restore the unstable DRUJ.

PMID- 15576226
TI  - Radiologic and patient-reported functional outcomes in an elderly cohort with
      conservatively treated distal radius fractures.
AB  - PURPOSE: There have been few prospective studies of elderly patients with
      conservatively treated distal radius fractures and little is known about the
      relationship between acceptable radiographic reduction and functional outcomes in
      this population. We hypothesized that acceptable fracture reduction (according to
      standard radiographic dorsal/volar tilt criteria) would be associated with better
      functional outcomes and greater satisfaction. METHODS: Seventy-four patients who
      were at least 50 years of age with conservatively managed distal radius fractures
      were recruited from 2 large urban emergency departments from January 2001 to
      December 2001. Patients with wrist fractures treated in the emergency department
      and discharged home were included; patients admitted to the hospital or who
      required surgical reduction were excluded. Standard lateral radiographs were
      taken after the final cast was removed. These were reviewed independently by a
      reference-standard musculoskeletal radiologist and the degree of dorsal/volar
      tilt was recorded. This value was dichotomized according to standard published
      dorsal/volar tilt criteria as acceptable (dorsal tilt <10 degrees or volar tilt
      <20 degrees ) or unacceptable (dorsal tilt >10 degrees or volar tilt >20 degrees
      ). The Medical Outcomes Study Short-Form 12 (SF-12); the Disabilities of the Arm,
      Shoulder, and Hand questionnaire; and a patient satisfaction survey were used to
      assess patient-reported outcomes 6 months after the injury. RESULTS: The average
      dorsal/volar tilt measured by the reference standard radiologist was 3.4 degrees
      (SD=13.6) dorsal; overall 47 patients (64%) were considered to have an acceptable
      radiographic reduction. Acceptable radiographic reduction was not associated with
      better generic physical or mental health status, lesser degrees of upper
      extremity disability, or greater satisfaction with outcomes than was unacceptable
      reduction. Overall 44 of 74 patients (59%) reported being satisfied or very
      satisfied with their functional status at 6 months. CONCLUSIONS: Contrary to our
      hypotheses we found that acceptable radiographic reduction (according to
      dorsal/volar tilt criteria) was not associated with better self-reported
      functional outcomes or increased satisfaction at 6 months in elderly patients
      with conservatively treated distal radius fractures.

PMID- 15576227
TI  - Assessment of instability factors in adult distal radius fractures.
AB  - BACKGROUND: The purpose of this study was to evaluate the radiographic outcome of
      unstable distal radius fractures treated by closed reduction and sugar tong
      splinting and to quantitatively evaluate Lafontaines' criteria of instability.
      METHODS: Fifty patients with 3 or more instability factors as described by
      Lafontaine were treated by finger trap traction, closed reduction, and sugar-tong
      splinting. They were evaluated radiographically for initial angulation, radial
      inclination, radial length, and palmar tilt at the time of injury, after
      reduction, and 1 week, 2 weeks, and 4 weeks after reduction. The fracture either
      maintained an adequate reduction or failed to maintain an adequate reduction and
      showed secondary displacement based on specific criteria. RESULTS: At 4 weeks
      after reduction 46% of these unstable distal radius fractures maintained an
      adequate reduction. Of the 54% of fractures that failed to maintain an adequate
      reduction, age was the only statistically significant predictor of secondary
      displacement. After obtaining an acceptable initial closed reduction, patients 58
      years of age were found to be at 50% risk for secondary displacement. The risk
      for displacement with an unacceptable radiographic result was found to increase
      with increasing age and decrease with decreasing age. CONCLUSION: In the closed
      management of these potentially unstable distal radius fractures, age was the
      only statistically significant risk factor in predicting secondary displacement
      and instability. These data help guide treatment by closed reduction and
      immobilization with serial x-rays or by surgical stabilization.

PMID- 15576228
TI  - Early corrective osteotomy for a malunited Colles' fracture using volar approach
      and calcium phosphate bone cement: a case report.
AB  - We report a case of malunion of the distal radius after a Colles' fracture
      treated with osteotomy using a volar approach combined with calcium phosphate
      bone cement grafting of the dorsal defect via a drill hole from the volar cortex
      6 weeks after the injury. One year and 4 months after surgery range of motion and
      grip strength were improved and x-rays of the wrist showed complete union of the
      distal radius with progressive absorption of the calcium phosphate bone cement.

PMID- 15576229
TI  - Treatment of radioulnar synostosis by radical excision and interposition of a
      radial forearm adipofascial flap.
AB  - A patient had radical excision of type II diaphyseal radioulnar synostosis and
      interposition of a radial forearm adipofascial flap. Neither adjuvant
      nonsteroidal anti-inflammatory medications nor radiation therapy were used. Three
      years after surgery the patient showed 90 degrees of pronation and 90 degrees of
      supination without any evidence of recurrence.

PMID- 15576230
TI  - Painful entrapment of the lateral antebrachial cutaneous nerve at the elbow.
AB  - PURPOSE: The purpose of this study was to report the diagnosis and management of
      entrapment neuropathy of the lateral antebrachial cutaneous nerve (LABCN)
      presenting as lateral elbow pain. METHODS: Twenty-three patients with lateral
      elbow pain were diagnosed with entrapment of the LABCN. Six patients also had
      paresthesia of the distal forearm. Diagnosis was made by clinical evaluation and
      confirmed with diagnostic injection of 1% lidocaine. Electrodiagnostic evaluation
      was positive in all patients. All patients were treated conservatively. Seven
      patients improved and 16 patients had surgical decompression of the LABCN at the
      elbow and distal arm with partial resection of the lateral margin of the biceps
      tendon. Postoperative follow-up evaluation averaged 45 months. RESULTS: Fourteen
      patients had complete relief of pain and 2 patients continued to have minimal to
      mild pain. Of the 6 patients who had preoperative paresthesia only 1 patient had
      persistent mild paresthesia of the radial side of the distal forearm. Range of
      motion and grip and pinch strength returned to normal values. All patients
      returned to their preoperative daily and work activities. CONCLUSIONS: Entrapment
      neuropathy of the LABCN should be considered in the differential diagnosis of
      elbow pain. Electrodiagnostic evaluation can be very useful in establishing and
      confirming the diagnosis. Surgical treatment of patients who do not respond to
      conservative treatment is simple yet effective in improving the patients'
      symptoms. Patients who present with paresthesia usually require surgical
      intervention because paresthesia represents a more progressive stage of the nerve
      entrapment.

PMID- 15576231
TI  - The prevalence of rotator cuff weakness in patients with injured hands.
AB  - PURPOSE: The purpose of this study was to document bilateral rotator cuff
      strength in patients with unilateral hand or wrist disorders. METHODS: Fifty
      seven patients who had suffered a unilateral injury or disorder isolated to their
      hand or wrist, distal to the distal radius, had their bilateral rotator cuff
      strength measured. RESULTS: A statistically significant decrease in strength was
      found in the ipsilateral shoulder for both elevation in the plane of the scapula
      (supraspinatus) and for elevated external rotation (infraspinatus). Younger
      patients and the nondominant extremity were affected more adversely. CONCLUSIONS:
      An increased prevalence of rotator cuff weakness is shown proximal to ipsilateral
      hand injuries or disorders.

PMID- 15576232
TI  - Low-grade myofibroblastic sarcoma of the distal phalanx.
AB  - Low-grade myofibroblastic sarcoma is a recently defined tumor that is part of the
      spectrum of malignant mesenchymal tumors, showing features of myofibroblastic
      differentiation. These tumors occur most commonly in the head and neck regions,
      especially in the tongue, and less frequently in the limbs, trunk, and
      abdominal/pelvic cavity. We describe a 51-year-old woman with a low-grade
      myofibroblastic sarcoma. The distal phalanx of the finger was amputated with a
      clear surgical margin. The treatment of this tumor should include a simple local
      excision with free surgical margins and a long clinical follow-up period with
      imaging studies. At the 28-month follow-up evaluation the patient was free from
      this tumor.

PMID- 15576233
TI  - Fritz de Quervain, MD (1868-1940): stenosing tendovaginitis at the radial styloid
      process.
AB  - Fritz de Quervain was the first surgeon to describe and treat chronic stenosing
      tendovaginitis at the radial styloid process. The current management of this
      condition differs little from his initial description and as a result the
      condition now bears his name. He and his mentor, Nobel Prize winner Theodor
      Kocher, advanced the understanding and treatment of thyroid disease, especially
      subacute nonsuppurative thyroiditis, another condition to which his name is
      attached. He was a pioneer of surgical technology and author of books and
      articles read worldwide and is largely responsible for the introduction of
      iodized table salt.

PMID- 15576234
TI  - Genotoxicity of airborne particulate matter: the role of cell-particle
      interaction and of substances with adduct-forming and oxidizing capacity.
AB  - Exposure to particulate matter (PM) is associated with several health effects
      including lung cancer. However, the mechanisms of particle-induced carcinogenesis
      are not fully understood. The main aim of this study was to investigate the
      genotoxicity of PM in relation to particle-cell interactions and to study the
      effect of removal of DNA-damaging substances by extraction of PM with different
      solvents. Genotoxicity was analyzed by means of the comet assay after exposure of
      cultured human fibroblasts to urban dust particles (SRM 1649). It was found that
      PM induced DNA damage in a dose-dependent manner and that cells interacting with
      PM suffered more DNA single-strand breaks relative to other cells. The
      genotoxicity of PM was significantly reduced after extraction with
      dichloromethane (DCM), dimethyl sulfoxide (DMSO) and water, but not with acetone
      and hexane. However, the insoluble particle core still induced DNA single-strand
      breaks. The extracts were further investigated in cell-free systems. Analysis of
      aromatic DNA adducts with 32P-HPLC showed that the DMSO and DCM extracts
      contained most of the DNA-reactive polyaromatic compounds (PACs). Further, the
      formation of 8-oxo-2'-deoxyguanosine (8-oxodG) upon incubation of the extracts
      with 2'-deoxyguanosine (dG) showed that the water extract contained most of the
      oxidizing substances. Thus, the genotoxicity of PM was caused both by adduct
      forming PACs and oxidizing substances as well as the insoluble particle-core.
      This study showed that all these factors together contribute to explaining the
      mechanisms of PM genotoxicity.

PMID- 15576235
TI  - Induction of micronuclei in mouse bone-marrow erythrocytes in association with
      hypothermia after administration of the sigma receptor ligand E-5842.
AB  - Oral administration of E-5842, a new sigma1 receptor ligand being developed as an
      antipsychotic drug, to male mice at single doses of 50, 100, 200 and 400 mg/kg
      produced marked and sustained decreases in rectal temperature. Both the intensity
      and the duration of the hypothermic effect increased with dose. Maximum decreases
      from the mean pre-administration temperature (36.2 degrees C) ranged from 7.5 to
      12.9 degrees C for animals receiving 50 and 400 mg/kg doses, respectively.
      Examination of bone-marrow smears obtained 24, 48 and 72 h after administration
      revealed a slight but statistically significant (p < 0.05) increase in the
      frequency of micronucleated polychromatic erythrocytes (MNPCE) at the 48 h
      sampling for animals receiving the 200 mg/kg dose. These animals showed decreases
      from pre-administration temperature of approximately 12 degrees C, with recovery
      being observed 24 h after administration. When the hypothermic effect of E-5842
      administration was avoided by housing treated animals under conditions of
      increased environmental temperature (30 degrees C) for 24 h, MNPCE frequency
      reverted to vehicle control values. Further, in E-5842-treated animals with an
      increased MNPCE frequency there was a shift in the distribution of the relative
      areas of micronuclei in MNPCE towards higher values. In addition, there was a
      statistically significant increase (p < 0.001) in the number of relatively large
      micronuclei (micronucleus diameter > or = 1/4 cytoplasm diameter) similar to that
      produced by administration of the mitotic spindle inhibitor colchicine (1 mg/kg),
      suggesting disturbance of mitotic apparatus as the possible underlying mechanism.
      The results suggest that the slight increase in MNPCE frequency observed 48 h
      after administration of a 200 mg/kg dose of E-5842 is due to a hypothermic effect
      and not to a direct effect of E-5842 on DNA.

PMID- 15576236
TI  - Influence of extraction parameters on the mutagenicity of soil samples.
AB  - The aim of this study was to investigate the influence of four extraction
      parameters (type of solvent, temperature, duration of extraction, and soil
      mass/solvent volume ratio) on the mutagenicity of soil extracts. Four urban soil
      samples were submitted to the micro-method adaptation of the Ames test on
      Salmonella typhimurium according to the following sequence: identification of the
      most sensitive strain (TA98 or TA100), the best solvent(s), the optimum
      extraction temperature and extraction time, and finally the optimal soil/solvent
      ratio. Extraction was thus performed using eight different solvents (distilled
      water, dichloromethane, acetonitrile, acetone, cyclohexane, methanol, hexane, or
      ethanol), two temperatures (room temperature or 37 degrees C), two durations (4
      or 24 h), and two soil mass/solvent volume ratios (1:2 or 1:10). The results show
      that strain TA98 was more sensitive than strain TA100, and the observed
      mutagenicity was expressed as number of TA98 revertants per mg of soil
      equivalent. No mutagenicity was induced by the distilled water extracts, whereas
      most of the organic solvent extracts induced a significant mutagenic response. A
      dichloromethane/acetone mixture appeared to be the best compromise for extraction
      of mutagens from the urban soils tested. Moreover, the present study showed that
      a higher mutagenic activity was generally obtained with a temperature of 37
      degrees C (compared to room temperature), with an extraction time of 24 h
      (compared to 4 h), and with a soil mass/solvent volume ratio of 1:10 (compared to
      1:2).

PMID- 15576237
TI  - Copper-mediated oxidative DNA damage induced by eugenol: possible involvement of
      O-demethylation.
AB  - Eugenol used as a flavor has potential carcinogenicity. DNA adduct formation via
      2,3-epoxidation pathway has been thought to be a major mechanism of DNA damage by
      carcinogenic allylbenzene analogs including eugenol. We examined whether eugenol
      can induce oxidative DNA damage in the presence of cytochrome P450 using [32P]-5'
      end-labeled DNA fragments obtained from human genes relevant to cancer. Eugenol
      induced Cu(II)-mediated DNA damage in the presence of cytochrome P450 (CYP)1A1,
      1A2, 2C9, 2D6, or 2E1. CYP2D6 mediated eugenol-dependent DNA damage most
      efficiently. Piperidine and formamidopyrimidine-DNA glycosylase treatment induced
      cleavage sites mainly at T and G residues of the 5'-TG-3' sequence, respectively.
      Interestingly, CYP2D6-treated eugenol strongly damaged C and G of the 5'-ACG-3'
      sequence complementary to codon 273 of the p53 gene. These results suggest that
      CYP2D6-treated eugenol can cause double base lesions. DNA damage was inhibited by
      both catalase and bathocuproine, suggesting that H2O2 and Cu(I) are involved.
      These results suggest that Cu(I)-hydroperoxo complex is primary reactive species
      causing DNA damage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine was
      significantly increased by CYP2D6-treated eugenol in the presence of Cu(II). Time
      of-flight-mass spectrometry demonstrated that CYP2D6 catalyzed O-demethylation of
      eugenol to produce hydroxychavicol, capable of causing DNA damage. Therefore, it
      is concluded that eugenol may express carcinogenicity through oxidative DNA
      damage by its metabolite.

PMID- 15576238
TI  - Abnormal DNA repair in selenium-treated human cells.
AB  - Selenium (Se), a micronutrient and an environmental, a chemical and an industrial
      agent in many products, can have genotoxic effects as well as antimutagenic
      and/or anticarcinogenic properties, depending on its concentration and oxidation
      state. We investigated the cytotoxic response of human osteosarcoma (U2OS) cells
      to low doses of sodium selenite and assayed their resistivity to cisplatin
      treatment and their capacity to reactivate cisplatin-treated reporter system,
      whose repair occurs through the transcription coupled repair (TCR) pathway, using
      the Host Cell Reactivation (HCR) Assay. In addition, we examined the ability of
      Se-treated human primary lymphocytes for normal double-strand breaks rejoining
      (DSBR) using the Challenge assay. Although, U2OS cells did not demonstrate
      cytotoxicity to all Se doses used, as measured by the cell proliferation MTT
      assay, their resistivity to cisplatin was significantly reduced. Moreover, Se
      treated cells exhibited a significant reduction in their capacity for TCR as
      compared with untreated control cells. Primary human blood lymphocytes
      demonstrated cytotoxicity to Se treatment at only a concentration of 10 microM.
      There were no significant increases in chromosome-type deletions or chromatid
      breaks or in mitotic indices in cells treated with Se alone or Se plus ionizing
      irradiation. However, dicentric chromosomes significantly increased upon
      treatment with 1 microM Se plus irradiation as compared with Se-untreated
      irradiated control. These findings demonstrate direct evidence on the inhibitory
      effect of inorganic Se on cellular DNA repair capacity.

PMID- 15576239
TI  - Micronuclei in peripheral blood lymphocytes of workers exposed to lead.
AB  - Lead plays an important role in many industrial processes. Although highly useful
      to man, lead has various types of toxic effects. There is constantly growing
      evidence of a relationship between the induction of chromosome breaks and an
      increased risk of onset of cancer. However, available data about the possible
      genotoxic and carcinogenic action of lead are conflicting. In this report we
      present the results of studies on lead concentrations in blood and the respective
      micronucleus frequencies in peripheral blood lymphocytes from workers employed in
      the recycling of automotive batteries in the surroundings of Porto Alegre,
      Brazil. We observed that in the occupationally exposed group, both lead
      concentration in peripheral blood and micronucleus frequency in lymphocytes were
      significantly higher compared to control (Z=6.35, P<0.0001 and Z=4.47, P<0.0001).
      The nuclear division index (NDI) values were significantly higher in the control
      group than in the exposed group (Z=2.13, P=0.0330), indicating a possible effect
      of Pb on nuclear proliferation. We also detected a negative correlation between
      micronuclei and progression of nuclear division (tau=-0.312, P=0.0129). There
      were no changes in micronucleus frequency between smoking and non-smoking workers
      exposed to lead (Z=0.03, P=0.9790). The only difference found between the groups
      of smokers and non-smokers was with respect to NDI, whose values were
      significantly higher among non-smokers (Z=1.98, P=0.0481).

PMID- 15576240
TI  - Etoposide exposure during male mouse pachytene has complex effects on crossing
      over and causes nondisjunction.
AB  - In experiments involving different germ-cell stages, we had previously found
      meiotic prophase of the male mouse to be vulnerable to the induction of several
      types of genetic damage by the topoisomerase-II inhibitor etoposide. The present
      study of etoposide effects involved two end points of meiotic events known to
      occur in primary spermatocytes--chromosomal crossing-over and segregation. By
      following assortment of 13 microsatellite markers in two chromosomes (Ch 7 and Ch
      15) it was shown that etoposide significantly affected crossing-over, but did not
      do so in a uniform fashion. Treatment generally changed the pattern for each
      chromosome, leading to local decreases in recombination, a distal shift in
      locations of crossing-over, and an overall decrease in double crossovers; at
      least some of these results might be interpreted as evidence for increased
      interference. Two methods were used to explore etoposide effects on chromosome
      segregation: a genetic experiment capable of detecting sex-chromosome
      nondisjunction in living progeny; and the use of FISH (fluorescence in situ
      hybridization) technology to score numbers of Chromosomes X, Y, and 8 in
      spermatozoa. Taken together these two approaches indicated that etoposide
      exposure of pachytene spermatocytes induces malsegregation, and that the findings
      of the genetic experiment probably yielded a marked underestimate of
      nondisjunction. As indicated by certain segregants, at least part of the
      etoposide effect could be due to disrupted pairing of achiasmatic homologs,
      followed by precocious sister-centromere separation. It has been shown for
      several organisms that absent or reduced levels of recombination, as well as
      suboptimally positioned recombination events, may be associated with abnormal
      segregation. Etoposide is the only chemical tested to date for which living
      progeny indicates an effect on both male meiotic crossing-over and chromosome
      segregation. Whether, however, etoposide-induced changes in recombination
      patterns are direct causes of the observed malsegregation requires additional
      investigation.

PMID- 15576241
TI  - Kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in vivo
      by aneuploidogens.
AB  - The aim of the present study was to make inferences about the cytotoxic and
      genotoxic action of the antineoplastic aneuploidogens, vinblastine and
      vincristine, by analyzing the kinetics of MN-PCE induction in mice in vivo. The
      kinetics of MN-PCE induction was assessed by taking blood samples from the tail,
      before the single i.p. injection of different doses of vinblastine or vincristine
      and every 8h after that. The analysis was done in groups consisting of three or
      four animals. The results indicate that both agents have similar kinetics of MN
      PCE induction which differs from the kinetics previously obtained for colchicine
      in the following aspects: (i) vinblastine and vincristine cause a longer delay
      after exposure, (ii) they produce a higher maximal velocity of induction, and
      (iii) higher doses give rise to more than one peak in the curve of MN-PCE
      frequency versus time. The results of the present study indicate that the
      different mechanisms of action of vinca alkaloids and colchicine are reflected in
      their kinetics of MN-PCE induction, and that such mechanisms could also explain
      the differences in their efficiency. Vinca alkaloids seem to block the cell
      division immediately, but the cell appears to be capable of reverting the
      blockage during the period of time corresponding to the first division. Moreover,
      evidence was obtained indicating that high doses could induce a long lasting
      aneuploidogen effect, probably related to the accumulation of vinca alkaloids
      that are either free or associated to tubulin.

PMID- 15576242
TI  - Correlates and determinants of child anthropometrics in Latin America: background
      and overview of the symposium.
AB  - In Latin America and the Caribbean (LAC) about one in six children under 5 years
      of age--or about 9 million children--suffer from longer-run undernourishment
      reflected in stunting. This paper introduces, places in perspective and presents
      a common micro analytical framework for the seven papers in this symposium that
      investigate the household and community determinants of child malnourishment in
      eight countries in LAC. These papers are the outcomes of a research project
      supported by the Inter-American Development Bank (IDB) Research Department Latin
      American and Caribbean Research Network Project on "Child Health, Poverty and the
      Role of Social Policies" in 2003-2004.

PMID- 15576243
TI  - Effects of land titling on child health.
AB  - This paper examines the impact of urban land titling on child health. We
      hypothesize that land titling may translate into positive effects on health
      through its impact on housing investments and household structure. To address
      selection concerns, we take advantage of a natural experiment of land occupation
      in a suburban area of Buenos Aires, Argentina, that ensures that the allocation
      of property rights is exogenous to the characteristics of the squatters. Our
      results show that in the titled parcels children enjoy better weight-for-height
      scores (but similar height-for-age scores), and teenage girls have lower
      pregnancy rates than those in untitled parcels.

PMID- 15576244
TI  - Geography and culture matter for malnutrition in Bolivia.
AB  - The prevalence of health problems and malnutrition in Bolivia is exceptionally
      high, even in comparison to other underdeveloped countries. This study analyzes
      the relationship between a two measures of child health--height-for-age and
      weight-for-age z-scores--and a set of physical and cultural determinants of child
      nutrition, including mother's characteristics, household assets and access to
      public services. The ultimate aim is to identify the most important determinants
      of child health and to measure the relative impact of each factor on the height
      and weight z-scores. A sequential strategy was adopted in order to estimate a two
      equation linear model with correlated error terms. A major finding points to
      geographical and cultural variables as main causes of nutritional status and
      highlights the role of mother's anthropometrical characteristics. This study uses
      data on over 3000 children gathered from a Demographic and Health Survey (DHS).

PMID- 15576245
TI  - Infant mortality and child health in Brazil.
AB  - Child health is a central issue in the public policy agenda of developing
      countries. Several policies aimed at improving child health have been implemented
      over the years, with varying degrees of success. In Brazil, such policies have
      triggered a significant decline in infant mortality rates over the last 30 years.
      Despite this improvement, however, mortality rates are still high compared to
      international standards. Moreover, there is considerable imbalance across
      Brazilian municipalities suggesting that various policies should be adopted. We
      investigate the determinants of infant mortality at the municipal level and
      provide an analysis of the factors affecting child health at the individual
      level. To analyze the mortality rate, we estimate static and dynamic panel data
      models using four censuses covering the period from 1970 to 2000. The demand for
      child health, on the other hand, is addressed through a household decision model,
      estimated using anthropometric data from the 1996 Standard of Living Survey. The
      results obtained indicate that a rise in sanitation, education and per capita
      income contributed to the decline of infant mortality in Brazil, with stronger
      impacts in the long run than in the short run. The fixed effects associated with
      county characteristics explain the observed dispersion in child mortality rates.
      The results from the decision model are confirmed by the findings of the
      mortality model: education, sanitation and poverty are the most important causes
      of poor child health in Brazil.

PMID- 15576246
TI  - Child health in rural Colombia: determinants and policy interventions.
AB  - We study the determinants of child anthropometrics on a sample of poor Colombian
      children living in small municipalities. We focus on the influence of household
      consumption, and public infrastructure, taking into account the endogeneity of
      household consumption using two different sets of instruments: household assets
      and municipality average wage. We find that both household consumption and public
      infrastructure are important determinants of child health. We have also found
      that the coverage of the piped water network positively influenced child health
      if the parents have some education.

PMID- 15576247
TI  - The role of maternal cognitive ability on child health.
AB  - Little is known about the mechanisms through which mother's cognitive ability
      operates in enhancing her children's health. This paper analyzes how maternal
      returns to cognitive ability on children's height reflect contemporaneous
      endowments and childhood background of the mother. Results suggest that maternal
      returns to cognitive ability on child height are less likely to reflect observed
      mother's childhood endowments as measured by parental transmission of knowledge
      or school quality, but are more likely to be associated with learning to be a
      mother, and with a better capacity to take advantage of household and community
      available resources.

PMID- 15576248
TI  - Private and public determinants of child nutrition in Nicaragua and Western
      Honduras.
AB  - We present a multivariate regression model of nutritional indicators, including
      interactions between education levels and overall community development, as well
      as estimates of community fixed effects, for two data sets: the first one is from
      a 2001 nationwide household survey in Nicaragua while the second set was
      collected in the Western regions of Honduras in 2002, as part of an evaluation
      process for a family entitlement program. Maternal stature, age difference with
      an older sibling, household size and income are seen as the main determinants of
      anthropometric development. Within the more homogeneous communities of Western
      Honduras, woman's education is also related to the child's nutritional status.
      The importance of individual community variables is much lower and the inclusion
      of community fixed effects does not alter the other parameters. However, in the
      Honduran sample, overall community development (assessed through the community
      fixed effects) has a small but significant and synergistic effect on the impact
      of child and household variables. The characteristics of this study and the
      complex design of entitlement programs prevent an adequate evaluation of those
      interventions within the poverty reduction strategies. The improvement of intra
      community targeting seems to be a key orientation for redesign. An improved socio
      economic situation, sound population and family policies, and an appropriate
      preventive public health care still are safe investments towards improvement of
      child health and nutrition.

PMID- 15576249
TI  - Poverty, health infrastructure and the nutrition of Peruvian children.
AB  - This paper offers empirical evidence on the impact of the expansion in health
      infrastructure of the 1990s upon child nutrition in Peru, as measured by the
      height for age z-score. Using a pooled sample of three rounds of the Peruvian
      DHS, I have controlled for biases in the allocation of public investments by
      using a district fixed effects model. The econometric analysis shows a positive
      effect of the expansion of the last decade in urban areas, but not in rural
      areas. Furthermore, the effect for urban children is highly non-linear and has a
      pro-poor bias, in the sense that the estimated effect is larger for children of
      less educated mothers. These findings support the idea that reducing distance and
      waiting time barriers is necessary to improve child health and nutrition in
      developing countries, but that we need more explicitly inclusive policies to
      improve the health of the rural poor, especially indigenous groups, that are
      caught in this type of poverty trap.

PMID- 15576250
TI  - The biological standard of living in the two Koreas.
AB  - Height data of North Korean escapees are analyzed to assess changes in their
      biological standard of living. In contrast to the population of South Korea, as
      well as to that of most of the rest of the world, North Koreans did not
      experience an increase in physical stature during the second half of the 20th
      century. The divergence between the height of North- and South-Koreans began
      among the birth cohorts of the late 1940s and became increasingly pronounced
      thereafter. This is an indication of the adverse socio-economic circumstances
      prevailing in the northern part of the Korean peninsula.

PMID- 15576251
TI  - Keeping it simple: encouraging walking as a means to active living.

PMID- 15576252
TI  - Has there been a delay in the age of regular smoking onset among African
      Americans?
AB  - BACKGROUND: It is not clear whether the decline in African American adolescent
      smoking in the 1980s reflected a delay in age of onset of regular smoking
      initiation rather than success in preventing initiation completely. PURPOSE: The
      purpose of this study is to identify whether the marked reductions in African
      American adolescent smoking in the 1980s were offset by increased initiation in
      young adults. METHODS: We combined data from the Tobacco Use Supplements of the
      1992-1993, 1995-1996, and 1998-1999 Current Population Surveys (n = 512,258), and
      reconstructed year of smoking initiation and calculated age-specific incidence of
      initiation from 1970 to 1992. We then compared detailed age-specific rates of
      initiation for two 5-year periods selected to be before and after the documented
      large declines in African American adolescent smoking. RESULTS: In the time
      period after marked declines in African American adolescent smoking (1987-1991),
      the incidence of initiation of regular smoking decreased for African Americans
      ages 14 to 16 and increased for ages 18 to 20. Such a delay was not as evident
      among non-Hispanic Whites. The delay that was slight in regular smoking
      initiation among African Americans relative to non-Hispanic Whites in 1975-79 had
      increased substantially by 1987-91. CONCLUSIONS: Reductions in African American
      adolescent smoking in the 1980s were offset by increased initiation among young
      adults ages 18 to 20 during this time period and suggest that the window for
      uptake of regular smoking shifted to older ages for African Americans more so
      than non-Hispanic Whites. Efforts to combat smoking should remain aggressive into
      young adulthood, when the tobacco industry's efforts to gain new smokers
      intensify.

PMID- 15576253
TI  - A preliminary study of one year of pedometer self-monitoring.
AB  - BACKGROUND: Long-term pedometer monitoring has not been attempted. PURPOSE: The
      purpose of this project was to collect 365 days of continuous self-monitored
      pedometer data to explore the natural variability of physical activity. METHODS:
      Twenty-three participants (7 men, 16 women; M age = 38 +- 9.9 years; M body mass
      index = 27.7 +- 6.2 kg/m2) were recruited by word of mouth at two southern U.S.
      universities. Participants were asked to wear pedometers at their waist during
      waking hours and record steps per day and daily behaviors (e.g., sport/exercise,
      work or not) on a simple calendar. In total, participants wore pedometers and
      recorded 8,197 person-days of data (of a possible 8,395 person-days, or 98%) for
      a mean of 10,090 +- 3,389 steps/day. Missing values were estimated using the
      Missing Values Analysis EM function in SPSS, Version 11.0.1. RESULTS: A mean of
      10,082 +- 3,319 steps/day was computed. Using the corrected data, differences in
      steps/day were significant for season (summer > winter, F = 7.57, p = .001), day
      of the week (weekday > weekend, F = 3.97, p = .011), type of day (workday vs.
      nonworkday, F = 9.467, p = .008), and participation in sport/exercise (day with
      sport/exercise > day without sport/exercise, F = 102.5, p < .0001). CONCLUSIONS:
      These data suggest that surveillance should be conducted in the spring/fall or
      that an appropriate correction factor should be considered if the intent is to
      capture values resembling the year-round average.

PMID- 15576254
TI  - Differences in resting cardiovascular parameters in 10- to 15-year-old children
      of different ethnicity: the contribution of physiological and psychological
      factors.
AB  - BACKGROUND: The health status of children in the North West Province of South
      Africa was examined using the Transition and Health during Urbanization in South
      Africa in Children study. This is an epidemiological, cross-sectional study for
      which 1,244 children between 10 and 15 years of age were recruited from 44
      schools. PURPOSE: Our objective was to investigate whether differences exist
      between resting cardiovascular parameters of Black, White, colored, and Indian
      children and evaluate the contribution of physiological and psychological
      factors. METHODS: Blood pressure was monitored with the Finapres apparatus. By
      means of the Fast Modelflo software program, the systolic blood pressure (SBP),
      diastolic blood pressure (DBP), mean arterial pressure, heart rate, cardiac
      output (CO), total peripheral resistance (TPR), and "Windkessel" compliance (Cw)
      of the arterial system were obtained. The psychological data were obtained by
      validated questionnaires. RESULTS: After correction for body mass index, the SBP
      of the White children was significantly higher (p < .05) than the SBP of the
      other ethnic groups. The DBP showed no significant differences. The TPR
      measurements of the Black and colored children were significantly higher (p <
      .05) than the TPR of the White children, and the Cw measurements of the Black and
      colored children were significantly lower than the Cw of the White children.
      Significant correlations (p < .05) were found between the SV, CO, TPR, Cw, and
      the total score on violence in the Black and colored children. CONCLUSIONS: There
      are differences in the resting cardiovascular parameters in the different ethnic
      groups studied. The higher levels of violence to which the Black and colored
      children are exposed could alter vascular sensitivity to sympathetic stimulation.
      This may contribute via the higher -adrenergic sensitivity to the pathogenesis of
      hypertension in their later lives.

PMID- 15576255
TI  - Religious orientation, aging, and blood pressure reactivity to interpersonal and
      cognitive stressors.
AB  - BACKGROUND: Research on religion and health suggests general health benefits for
      those who are more religiously involved. Particular aspects of religiosity that
      may influence this finding, however, have not been sufficiently investigated.
      PURPOSE: This study was designed to explore the relationship between religious
      orientation (intrinsic, extrinsic) and blood pressure reactivity among older
      (over 60 years) and younger (18-24 years) adults exposed to two qualitatively
      different laboratory stressors (cognitive, interpersonal). METHODS: Participants
      were categorized as exhibiting either a predominantly intrinsic or extrinsic
      religious orientation based on scores on the Religious Orientation Scale. They
      were subsequently exposed (in counterbalanced order) to two laboratory stressors
      that varied in terms of whether an interpersonal confrontation was involved.
      Measures of blood pressure were obtained at baseline and during stressor
      presentation. RESULTS: Analyses indicated that older extrinsically religious
      individuals demonstrated exaggerated reactivity compared to younger participants
      and older intrinsically religious individuals. Older intrinsically religious
      participants did not differ from younger persons. Similar results were found for
      analysis of baseline data. Extrinsic participants had greater reactivity during
      the interpersonal confrontation condition than did intrinsic individuals.
      CONCLUSIONS: These findings suggest that religious orientation may be an
      important variable to study regarding cardiovascular reactivity in, particularly,
      older adults.

PMID- 15576256
TI  - Social support and religiosity as coping strategies for anxiety in hospitalized
      cardiac patients.
AB  - BACKGROUND: Prospective studies have demonstrated that anxiety is associated with
      an increased risk of mortality and sudden cardiac death. There is therefore a
      need to understand what factors contribute to anxiety in patients with coronary
      heart disease (CHD). PURPOSE: This study examined whether social support and
      religiosity are individually or jointly associated with lower anxiety in cardiac
      patients. METHODS: Anxiety, perceived social support, and religiosity were
      assessed in 228 (71% male, 29% female) hospitalized CHD patients aged 62 +- 11
      years. RESULTS: Higher levels of social support were related to lower levels of
      state and trait anxiety (state anxiety, r = -.26, p < .01; trait anxiety, r = 
      .30, p < .01;). Religiosity was related to lower state anxiety (r = -.27, p <
      .01) but only modestly related to lower trait anxiety (trait anxiety, r = -.18, p
      < .01). The relationship between religiosity and trait anxiety was no longer
      significant after controlling for social support (p = .26). CONCLUSIONS: These
      findings suggest that religiosity and social support provide a buffer against
      anxiety in CHD patients and that higher levels of social support may account for
      the relationship between religiosity and trait anxiety. These findings underscore
      the importance of social support and religiosity as buffers against distress,
      with possible implications for prognosis in a patient group where high levels of
      anxiety appear to confer increased risk of mortality.

PMID- 15576257
TI  - A community-based walking trial to improve neighborhood quality of life in older
      adults: a multilevel analysis.
AB  - BACKGROUND: Few studies have considered the neighborhood as a context in which to
      examine the physical activity and quality of life relationship. PURPOSE: The goal
      of this study was to evaluate the effects of a neighborhood walking program on
      quality of life among older adults. It was designed as a randomized trial
      involving a multilevel design with neighborhoods corresponding to primary
      sampling units and residents to secondary units. METHODS: Five hundred eighty-two
      community-dwelling senior residents (65 years of age or older) in neighborhoods
      in the northeast metropolitan area of Portland, Oregon, were recruited through
      telephone, direct mail, and referrals. The walking intervention was delivered at
      the neighborhood level. Neighborhoods (N = 56) were randomly assigned to a 6
      month, 3 times per week, leader-led walking group activity (n = 28) or an
      information-only control group (n = 28). Primary outcome measures included SF-12
      (Physical, Mental summary scores) and life satisfaction (SWLS); the secondary
      outcome measure was neighborhood walking activity, assessed at baseline, 3
      months, and 6 months of the study period. RESULTS: Compared to the control
      neighborhoods, results from multilevel, longitudinal analyses indicated
      significant improvements in the primary outcomes of SF-12 Physical (p < .05), SF
      12 Mental (p < .05) summary scores, and SWLS (p < .05), over the course of the 6
      month intervention. A significant increase was also observed in the secondary
      outcome of walking activity (p < .05). CONCLUSIONS: Implementing a neighborhood
      based walking program of low to moderate intensity is feasible and beneficial for
      promoting quality of life among senior residents at a community level.

PMID- 15576258
TI  - Inhibited interpersonal coping style predicts poorer adherence to scheduled
      clinic visits in human immunodeficiency virus infected women at risk for cervical
      cancer.
AB  - BACKGROUND: One of the most common gynecologic conditions among HIV+ women is
      cervical dysplasia, the precancerous phase of cervical cancer. Therefore,
      adherence to gynecology visits may be among the most important health care
      practices for HIV+ women. However, no research has evaluated the psychosocial
      factors associated with health care practices among HIV+ women at risk for
      cervical cancer. PURPOSE: This study examined the relationship between inhibited
      interpersonal coping style and adherence to primary care and
      obstetrics/gynecology visits in HIV+ women with Human Papillomavirus (HPV)
      infection. METHODS: Twenty-eight HIV-1 seropositive Black, non-Hispanic women
      underwent a psychosocial interview, blood draw, and gynecologic examination. The
      Millon Behavioral Health Inventory was used to assess coping style. Medical chart
      review was used to assess adherence to scheduled special immunology clinic visits
      for 24 months following study entry. RESULTS: Results suggested that greater
      inhibited coping style significantly predicted greater nonadherence to clinic
      visits during 1-year (beta = .45, p = .04) and 2-year (beta = .58, p = .02)
      follow-up, even after controlling for the possible confounding effects of recent
      depressed mood on adherence. Social support satisfaction did not mediate the
      relationship between inhibited coping style and nonadherence. CONCLUSIONS: These
      findings suggest that interpersonal coping style assessment may be a useful tool
      in predicting adherence in HIV+ women with HPV. Future research should assess the
      effect of psychosocial interventions on coping style, adherence, and cervical
      dysplasia in HIV+ women with HPV.

PMID- 15576259
TI  - Illness-specific and general perceptions of social relationships in adjustment to
      rheumatoid arthritis: the role of interpersonal expectations.
AB  - BACKGROUND: Adjustment to rheumatoid arthritis (RA) may be made more difficult
      when patients are unable to meet the expectations of family and friends about how
      well they are coping. PURPOSE: This study investigated the influence of illness
      specific interpersonal expectations and general indices of social interactions on
      depressive symptoms among 39 women with RA (M age = 46.9 years; M disease
      duration = 11.2 years). METHODS: Female patients with RA and their spouses were
      recruited from an outpatient rheumatology clinic at an urban university hospital.
      Participants completed questionnaires at home and returned them to the research
      staff in prepaid, stamped envelopes. RESULTS: Results showed a significant
      correlation between spousal expectations and patients' perceived inability to
      meet them. Further, hierarchical regression analyses indicated that even when
      controlling for disease severity and traditional measures of social interactions
      (e.g., social support, perceived criticism, and general quality of the dyadic
      relationship), patient's perceived inability to meet spousal expectations
      contributed unique variance in depressive symptoms. CONCLUSIONS: These results
      suggest that adjustment to RA is not due entirely to the general features of
      social relationships, but additionally reflect specific aspects of the chronic
      illness milieu where spousal expectations and the patient's perceived inability
      to meet them are also related to adjustment.

PMID- 15576260
TI  - Associations between relationship support and psychological reactions of
      participants and partners to BRCA1 and BRCA2 testing in a clinic-based sample.
AB  - BACKGROUND: Despite the potential importance of communication about genetic
      testing between test participants and their significant others, little is known
      about social support and communication between women undergoing BRCA1 and BRCA2
      testing and their partners. PURPOSE: The aims of this longitudinal study were to
      examine communication about genetic testing during and following testing and to
      evaluate whether communication is associated with psychological distress reported
      by test participants and their partners. METHODS: Participants were 153 women who
      were undergoing genetic testing and 118 partners of women undergoing testing.
      Relationship communication and distress were evaluated at the time of pretest
      education and 6 months postdisclosure. RESULTS: Overall, the decision to undergo
      testing was discussed by the majority of test participants and partners, and most
      couples felt their partners were supportive. Most women disclosed their results
      to their partners. Longitudinal analyses suggested that less support and
      protective buffering were associated with greater distress 6 months
      postdisclosure among test participants, whereas lower comfort in sharing concerns
      and partner support were associated with lower distress 6 months postdisclosure
      among partners. CONCLUSIONS: The results of this study suggest that the majority
      of couples respond supportively during the test experience, but for a small
      subset of couples the process can strain the relationship. Partner support during
      this process is important, particularly for test participants dealing with an
      uninformative test result.

PMID- 15576261
TI  - A primer on current evidence-based review systems and their implications for
      behavioral medicine.
AB  - BACKGROUND: Multiple review systems have been established within medicine and
      psychology to evaluate and disseminate research findings to clinical practice.
      PURPOSE: Within this article, five evidence-based review systems are reviewed to
      inform the development or the use of an evidence review system for the behavioral
      medicine field. METHODS: Each review system is described on several dimensions:
      history of the review system, the review process, and details about
      translation/sustainability efforts. RESULTS: Various factors from each system
      have been identified that would benefit a behavioral medicine evidence review
      system, such as a discussion of clinical features that influence the
      generalizability of review findings (i.e., the American Psychiatric Association)
      and the use of pre-review protocols (i.e., the Cochrane Collaboration).
      CONCLUSIONS: Although each review system has limitations, it is important for
      behavioral medicine to join one system because (a) systematic reviews are the
      only feasible means to evaluate and judge the usefulness of our interventions,
      and (b) reviews can inform policy, and, with effort, influence patient well
      being. This group of behavioral medicine experts recommends that the Cochrane
      Collaboration review behavioral medicine interventions.

PMID- 15576265
TI  - Difficult delivery of the impacted fetal head during cesarean section:
      intraoperative disengagement dystocia.
AB  - Cesarean section is commonly perceived as a simple and safe alternative to
      difficult vaginal birth. However, several trends in obstetrical practice may act
      in concert to cause impaction of the fetal head during the second stage of labor
      or, more commonly, following failed instrumental delivery. Subsequently,
      difficult and potentially traumatic disengagement of the deeply wedged head
      during cesarean section occurs. The maneuvers to disengage the wedged head
      include pushing (bimanual or by an assistant) the head through the vagina or,
      alternatively, pulling the infant's feet through the uterine incision. Although
      both methods may cause serious maternal and neonatal complications, available
      data seem to favor the pulling method and better outcome seems to depend on
      adequate uterine relaxation, the patient's position during operation, and special
      attention to the uterine incision. More data are needed to establish the
      frequency and extent of intraoperative disengagement dystocia and to determine
      the management protocol that carries the lowest risk in such circumstances.

PMID- 15576266
TI  - Breech presenting twin A: is vaginal delivery safe?
AB  - The aim of our study was to compare the neonatal outcome of vaginally delivered
      breech-presenting twins (VD) to those delivered by cesarean (CS). Maternal and
      neonatal charts of all live, non-anomalous twins delivered at > or =25 weeks of
      gestation, in a single tertiary care center, over an 11-year period were
      reviewed. Of 517 twins delivered, 130 breech-presenting twins were analyzed.
      Thirty-five (26.9%) were delivered vaginally and 95 (73.1%) by cesarean. More
      patients presented in labor with advanced cervical dilation in the VD compared to
      the CS group. There was no difference in the incidence of respiratory distress
      syndrome, intraventricular hemorrhage, need for mechanical ventilation, length of
      nursery stay or neonatal mortality rate when twin A was compared in the two
      groups. However, one breech-presenting twin in the VD group had a traumatic
      delivery at 32 weeks of gestation that caused a spine fracture followed by
      immediate neonatal death. Although there seems to be no compromise in the
      immediate neonatal outcome of breech-presenting twins delivered vaginally
      compared to those delivered by cesarean, the case of head entrapment that led to
      intrapartum death is quite alarming. Based on our study, we cannot advocate
      normal vaginal delivery when twin A is non-vertex: cesarean seems to be a safer
      route of delivery.

PMID- 15576267
TI  - Maternal serum interleukin-1 beta, -6 and -8 levels and potential determinants in
      pregnancy and peripartum.
AB  - AIMS: To measure maternal serum interleukins (IL) in pregnancy, delivery and
      early puerperium, and to identify their potential determinants. METHODS:
      Prospective longitudinal measures of serum IL-1 beta, IL-6 and IL-8 in 38 healthy
      pregnant women at antenatal visits, through labor and delivery, with clinical
      correlates (infection, vaginal hemorrhage and anemia) recorded by questionnaire.
      RESULTS: Pregnancy IL levels remained consistently low. IL-1 beta increased
      shortly before delivery, then returned to pregnant levels, except where blood
      loss exceeded 500 ml. IL-6 and IL-8 rose at labor onset and exceeded pregnancy
      levels through postpartum day three. Postpartum IL-6 was higher after non
      elective cesarean section than after spontaneous delivery (P < 0.0001), and where
      blood loss exceeded 500 ml. IL-6 and IL-8 were higher with systemic infection
      during delivery (P < 0.0001) and on postpartum day one (P < 0.05); IL-8 was
      higher in anemia (delivery: P < 0.005; postpartum day 1: P < 0.05). Differences
      due to delivery mode and systemic infection remained significant after correction
      for other conditions. CONCLUSIONS: Labor-dependent inflammation increases all IL
      levels at delivery. Further studies with larger sample sizes are required to
      establish reference values differentiating physiology from pathology as an aid to
      peripartum management.

PMID- 15576268
TI  - Comparison between HELLP syndrome, chronic hypertension, and superimposed
      preeclampsia on chronic hypertension without HELLP syndrome.
AB  - AIM: To compare perinatal outcome of patients with HELLP syndrome to that of
      patients with chronic hypertension and superimposed preeclampsia on chronic
      hypertension without HELLP syndrome. METHODS: We retrospectively evaluated the
      perinatal outcome of 147 pregnancies complicated by the HELLP syndrome, chronic
      hypertension, and superimposed preeclampsia on chronic hypertension without HELLP
      syndrome. RESULTS: Gestational age at delivery and birthweights were lower among
      women with HELLP syndrome than among women with superimposed preeclampsia and
      chronic hypertension (P < 0.05). There were no statistically significant
      differences among the three groups with respect to intrauterine growth
      retardation, respiratory distress syndrome, intraventricular hemorrhage,
      necrotizing enterocolitis, Apgar score, admission to neonatal intensive care
      unit, overall rate of cesarean delivery and cesarean delivery rate for fetal
      distress. The total perinatal mortality rate was 17% (28/147) and was more
      frequent in the HELLP group (27%). Multivariate logistic regression analysis
      showed that gestational age at delivery (RR 0.45) and birthweight (RR 0.99) were
      risk factors for adverse outcome. CONCLUSIONS: Perinatal outcome is primarily
      influenced by gestational age at delivery and birthweight independent of the
      severity of the hypertensive status of pregnant women.

PMID- 15576269
TI  - Fetal scalp pH and ST analysis of the fetal ECG as an adjunct to CTG. A multi
      center, observational study.
AB  - OBJECTIVE: To evaluate the relationships between scalp-pH and CTG plus ST
      waveform analysis of the fetal ECG (STAN) clinical guidelines as indicators of
      intrapartum hypoxia in term fetuses born with cord artery acidemia. STUDY DESIGN:
      Data from 6999 term deliveries monitored by the STAN (R) S 21 as part of an EU
      multi-center study on clinical implementation of the STAN methodology for
      intrapartum fetal surveillance were analyzed. We identified 911 cases where a
      scalp-pH was obtained, including 53 cases with cord artery acidemia (pH < 7.06).
      Lag times between ST events and scalp-pH and time to delivery were related to
      cord artery metabolic and respiratory acidosis and neonatal outcome. RESULTS: 43
      fetuses were identified by CTG plus ST as being in need of intervention 31 (25
      46) minutes before delivery (median, 95% Cl). In five, no indications were given
      and in another five there were inadequate data. Fifteen cases with metabolic
      acidosis required special neonatal care, all 14 cases adequately monitored on
      STAN had indications to intervene for 19 minutes or more. In 30 adequately
      recorded cases, fetal blood sampling (FBS) was obtained within the last hour of
      labor. In 22 cases, FBS was obtained 13 (7-24) minutes after STAN guidelines had
      indicated abnormality and in eight no ST changes had occurred at time of FBS. The
      corresponding FBS data were pH 7.10 (7.01-7.15) and pH 7.21 (7.08-7.31),
      respectively, P = 0.01. In cases of metabolic acidosis, scalp-pH fell 0.01 units
      per minute after a baseline T/QRS rise was recorded during the second stage of
      labor. Apart from one newborn that died at 2 h from E. Coli septicemia, none of
      the neonates were affected neurologically. CONCLUSION: Cardiotocography plus ST
      analysis provides accurate information about intrapartum hypoxia similar to that
      obtained by scalp-pH.

PMID- 15576270
TI  - Effects of nitric oxide and prostacyclin on hemodynamic response by big
      endothelin-1 in near term fetal sheep.
AB  - AIMS: To measure plasma concentrations of endothelin (ET)-1, NO metabolites
      (nitrate/nitrite; NOx) and 6-keto PGF1 alpha (PGF1 alpha) in maternal and fetal
      sheep blood, and to evaluate the effects of big ET-1 on hemodynamic response,
      blood gases and NO and 6-keto PGF1 alpha production in near term fetal sheep.
      METHODS: Hemodynamic parameters were measured during infusion of big ET-1 into
      the carotid vein in chronically catheterized fetal sheep on day 125 of gestation.
      Fetal arterial blood samples were obtained for ET-1, PGF1 alpha) and
      nitrate/nitrite (NOx) measurements. RESULTS: ET-1, NOx and PGF1 alpha plasma
      concentrations were all significantly higher in fetal compared with the maternal
      plasma. Big ET-1 significantly decreased fetal systolic and diastolic blood
      pressure and significantly increased fetal heart rate. Big ET-1 stimulated plasma
      PGF1 alpha), but not NOx , concentration. CONCLUSIONS: Circulatory regulating
      factors in the fetus were up-regulated. The effects of ET-1 on fetal hemodynamic
      response may be mediated via prostacyclin, but not via the NO pathway.

PMID- 15576271
TI  - Strategy for management of newborns with cervical teratoma.
AB  - BACKGROUND: Cervical teratomas are extremely rare tumors with high perinatal
      mortality and morbidity rates. OBJECTIVE: To compare our experience and outcome
      in newborns with cervical teratoma with similar reports from the literature, in
      order to propose a structured approach. METHODS: A retrospective review of seven
      patients treated between 1986 and 2000 was performed. The results of these seven
      patients were compared with and added to a series of 44 well-documented patients
      retrieved from the literature. RESULTS: In four of the seven patients, the
      diagnosis was not suspected antenatally. Three of the patients survived, one
      died. In the other three, the diagnosis was made antenatally. Two were born using
      the ex-utero intrapartum treatment (EXIT) procedure, one by planned cesarean
      section. Only one of these three survived. Mortality in the total series of 51
      patients was 33% overall, and 46% in the group in which the diagnosis had been
      made antenatally. Peri- and post-operative complications were reported in 27%.
      Although larger tumors caused polyhydramnios more frequently than smaller tumors,
      and were associated with more severe respiratory distress, the relationship
      between tumor volume at birth and final outcome could not be established. This
      makes difficult the identification of fetuses with a disastrous prognosis.
      CONCLUSION: Although mostly benign, cervical teratomas are still associated with
      high mortality rates. Timely antenatal diagnosis is indispensable in reducing
      morbidity and mortality caused by upper airway obstruction. A structured approach
      to the management of cervical teratoma is proposed.

PMID- 15576272
TI  - Predicting neonatal outcomes: birthweight, body mass index or ponderal index?
AB  - AIMS: To compare birthweight (BW), body mass index (BMI) and ponderal index (PI)
      as predictors of selected short-term (ST) outcomes, namely Neonatal Intensive
      Care Unit (NICU) admission and prolonged hospitalization (PH), among newborn (NB)
      infants. METHODS: Data was collected prospectively on 9,226 infants born during
      one year at nine tertiary care hospitals in Greater Beirut, Lebanon. The
      predictive abilities of BW, BMI and PI were compared using the area under the
      receiver operator characteristic (ROC) curves and sensitivity analysis was
      performed at the optimal cut-off points for the best anthropometric measurement.
      RESULTS: The area under the ROC curve suggested superior discriminative power for
      BW as compared to BMI or PI, as a predictor of NICU admission (ROC area = 0.73)
      and PH (ROC area = 0.74). The optimal BW cut-off point was 2750 g (sensitivity:
      0.49; specificity: 0.89) and 2950 g (sensitivity: 0.62; specificity: 0.78) for
      NICU admission and PH, respectively. CONCLUSION: In our population of NB infants,
      BW--a crude measure of fetal growth--is a better predictor than either BMI--a
      measure of adiposity in adults and children--or PI--a measure of thinness at
      birth--for selected ST outcomes in NB infants.

PMID- 15576273
TI  - Markers of platelets activation, CD 62P and soluble P-selectin in healthy term
      neonates.
AB  - Nearly the same expression of CD 62P antigen was found on the platelets of
      neonates in the vein as in the artery, in both females and males. SP-selectin
      concentrations in sera were elevated in the vein in comparison to the artery,
      higher values being noted in females than in males. The activation of platelets
      occurs at the time of birth. The platelets of female neonates are more activated
      than those of male neonates.

PMID- 15576274
TI  - Detection of parvovirus B19, cytomegalovirus and enterovirus infections in cases
      of intrauterine fetal death.
AB  - AIMS: Maternal infections with parvovirus B19, cytomegalovirus (CMV) and
      enterovirus have been associated with intrauterine fetal death (IUFD), but the
      incidence of these infections is not clear. This prospective study was conducted
      to estimate this incidence. METHODS: A prospective study of 38 months was
      conducted on cases of IUFD referred to Huddinge University Hospital, Stockholm,
      Sweden. Placental biopsies, fetal blood and amniotic fluid were collected from
      cases of IUFD (n=52). Placental biopsies from normal pregnancies at term (n=53)
      were used as controls. These tissues were examined for parvovirus B19 DNA, CMV
      DNA and enterovirus RNA using polymerase chain reaction (PCR). Maternal viral
      serology was measured in 46 cases and virus isolation for enterovirus in maternal
      stool samples was performed in 31 cases. RESULTS: Viral nucleic acid was
      recovered in at least one tissue sample from six cases of fetal death (parvovirus
      B19 in two cases, CMV in three and enterovirus in one), while all placental
      biopsies from controls were found negative. Serological signs of primary maternal
      infection were found in two of the cases, and virus isolation for enterovirus was
      negative in all samples examined. CONCLUSION: Parvovirus B19, CMV and enterovirus
      may be considered as etiologic agents in cases of fetal death. PCR on placental
      and/or fetal tissue improves diagnostic accuracy for these infections.

PMID- 15576275
TI  - Plasma endothelin-1 and clinical manifestations of neonatal sepsis.
AB  - AIM: To determine whether plasma endothelin-1 (ET-1) relates to clinical
      manifestations of sepsis in the newborn, especially with systemic hypotension,
      acidosis, severe hypoxemia (which may represent pulmonary hypertension) and
      oliguria. METHODS: Prospective study of 35 consecutive newborns with clinical
      sepsis: 22 with hemoculture-positive (HC+) sepsis and 13 hemoculture-negative (HC
      ). Plasma ET-1 concentrations were measured within 2 days of the diagnosis of
      sepsis. SNAP-II severity score was performed at the time of highest clinical
      severity. RESULTS: Newborns with HC+ sepsis had higher plasma ET-1 concentrations
      and SNAP-II scores (especially PO 2 /FiO 2 ratio) than HC- septic children.
      Plasma ET-1 concentrations increased linearly with each item of the SNAP-II
      score, but only reached significant differences in lowest mean blood pressure
      (P=0.030), lowest pH (P=0.048), multiple seizures (P=0.010) and lowest urine
      output (P=0.013). Leukocyte count, immature/total neutrophil ratio and C-reactive
      protein value were not different. Each item of the SNAP-II score was
      independently related only to ET-1 level. Oliguria, acidosis and systemic
      hypotension were more correlated (R 2 >0.5). CONCLUSIONS: Plasma ET-1 levels in
      neonatal sepsis are related to the severity of clinical manifestations,
      especially oliguria, acidosis and systemic hypotension.

PMID- 15576276
TI  - Noncompaction of the left ventricular myocardium diagnosed in pregnant woman and
      neonate.
AB  - Noncompaction of the left ventricular myocardium (NCLV) is an uncommon congenital
      cardiomyopathy with poor prognosis. We describe a case of NCLV that developed in
      a pregnant woman and her neonate. A nulliparous woman was referred at 24 weeks'
      gestation due to dyspnea and fetal hydrops. Maternal echocardiography
      demonstrated NCLV with characteristic findings of prominent and excessive
      ventricular trabeculations and deep intertrabecular recesses in the left
      ventricle. An M-mode echocardiography suggested depressed left ventricular
      systolic function. A fetal echocardiography at 24 weeks' gestation demonstrated
      cardiomegaly, but morphologic findings were not definitive for NCLV. An emergency
      cesarean section was performed due to maternal heart failure. A neonatal
      echocardiography diagnosed NCLV with depressed left ventricular systolic
      function. The neonate died of cardiac failure on the second day of life. Autopsy
      confirmed the echocardiographic findings. Since patients with NCLV may develop
      heart failure, multidisciplinary management is mandatory. In addition, awareness
      of familial occurrence of NCLV should be kept in mind for early diagnosis in the
      fetus and neonate.

PMID- 15576277
TI  - Ventricular bigeminy misdiagnosed as fetal bradycardia by cardiotocography--the
      value of non-invasive fetal electrocardiography.
AB  - We document the value of non-invasive fetal electrocardiography (fECG) in a case
      of fetal arrhythmia in which an unnecessary cesarean section was almost
      performed. The fetal heart rate (fHR) was 60-70 beats per minute (bpm) on the
      cardiotocography (CTG), with occasional, sudden fluctuations to 130 bpm. This was
      probably a result of the technical limitations of the CTG.

PMID- 15576278
TI  - Prolonged fetal bradycardia as the presenting clinical sign in Streptococcus
      agalactiae chorioamnionitis.
AB  - Group B Streptococcus remains a leading infectious cause of neonatal morbidity
      and mortality. We report a case of a 37 weeks' gestation infant with severe birth
      asphyxia, status epilepticus and GBS chorioamnionitis, in which a prolonged fetal
      bradycardia was the only prenatal clinical sign.

PMID- 15576279
TI  - Changes of blood pressure and heart rate variability precede a grand mal seizure
      in a pregnant woman.
AB  - In order to evaluate blood pressure and heart rate variability as a potent
      diagnostic tool for different hypertensive pregnancy disorders we started a
      clinical trial recording these variables in early pregnancies predisposed for
      preeclampsia. During routine measurements one of the patients experienced a grand
      mal epileptic seizure. Since the parameters of both heart rate and blood pressure
      variability were sequentially altered immediately before the seizure, this case
      report provides an interesting insight into autonomic cardiovascular control in a
      developing convulsive fit and the pathophysiological generation of a grand mal
      seizure in pregnancy.

PMID- 15576280
TI  - Myocardial infarction in early pregnancy.
AB  - Acute myocardial infarction (AMI) during pregnancy is usually transmural and
      occurs in late pregnancy with a peak incidence during the peripartum or
      postpartum periods. We report a pregnancy-related AMI, which occurring as early
      as the first trimester, was treated conservatively with antithrombotic and anti
      ischemic drugs both acutely and through the rest of the ultimately successful
      pregnancy.

PMID- 15576281
TI  - The baby and the bathwater--a comment.

PMID- 15576282
TI  - Reply to the opinion paper "The baby or the bathwater: which one should be
      discarded?".

PMID- 15576283
TI  - Therapeutic drug monitoring in clinical toxicology: current strategies, thoughts
      and views on the future.

PMID- 15576284
TI  - Therapeutic monitoring of immunosuppressant drugs. Where are we?
AB  - The emergence of specific immunosuppressive drugs (cyclosporine, tacrolimus,
      mycophenolate mofetil and sirolimus) during the last two decades has contributed
      dramatically to the success of organ transplantation. However, optimum balance
      between therapeutic efficacy and the occurrence of side effects has been a real
      challenge for physicians, mainly due to inter- and intra-patient variability
      arising from pharmacokinetic, pharmacogenetic and pharmacodynamic individual
      properties. Therapeutic drug monitoring, defined as the measurement and
      interpretation of concentrations of these drugs in biological fluids, with as a
      final objective the prediction of organ responses, became an integral part of
      transplant protocols. New analytical techniques became available with different
      performances in terms of specificity and sensitivity. In addition, there has been
      progress in understanding the mechanisms of action of these drugs that have
      implications for the development of better monitoring strategies and for their
      coprescription. The purpose of this review is to examine the current strategies
      in use for the therapeutic drug monitoring of immunosuppressant drugs and to
      discuss some of the factors that impinge on the monitoring of these drugs.

PMID- 15576285
TI  - Therapeutic drug monitoring of non-tricyclic antidepressant drugs.
AB  - Therapeutic drug monitoring (TDM) of many of the tricyclic antidepressants (TCAs)
      has been demonstrated to be of clear clinical value. This article reviews studies
      of TDM for the selective serotonin reuptake inhibitors (SSRIs) and other non
      tricyclic antidepressants such as venlafaxine, nefazodone, trazodone, mianserin
      and bupropion. No definitive therapeutic concentrations have been demonstrated
      for these agents, nor have levels indicative of toxicity been reported. The major
      benefit of TDM for these agents would appear to be in the assessment of the
      apparently treatment-refractory depressed patient, to determine whether such lack
      of response is related to inadequate levels that would suggest either poor
      compliance, ultra-rapid metabolism, or drug interactions leading to induction of
      metabolising enzymes. Potential future applications of TDM, in conjunction with
      genotyping of cytochrome P450 enzymes and pharmacogenomic evaluations, are
      discussed.

PMID- 15576286
TI  - The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti
      cancer drug treatment.
AB  - Therapeutic drug monitoring generally focuses on the plasma compartment only.
      Differentiation between the total plasma concentration and the free fraction
      (plasma water) has been described for a number of limited drugs. Besides the
      plasma compartment, blood has also a cellular fraction which has by far the
      largest theoretical surface and volume for drug transport. It is with anti-cancer
      drugs that major progress has been made in the study of partition between the
      largest cellular blood compartment, i.e., erythrocytes, and the plasma
      compartment. The aim of the present review is to detail the progress made in
      predicting what a drug does in the body, i.e., pharmacodynamics including
      toxicity and plasma and/or red blood cell concentration monitoring. Furthermore,
      techniques generally used in anti-cancer drug monitoring are highlighted. Data
      for complex Bayesian statistical approaches and population kinetics studies are
      beyond the scope of this review, since this is generally limited to the plasma
      compartment only.

PMID- 15576287
TI  - Therapeutic drug monitoring of old and newer anti-epileptic drugs.
AB  - The aim of the present paper is to provide information concerning the setting up
      and interpretation of therapeutic drug monitoring (TDM) for anti-epileptic drugs.
      The potential value of TDM for these drugs (including carbamazepine, clobazam,
      clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam,
      oxcarbazepine, pheneturide, phenobarbital, phenytoin, primidone, tiagabine,
      topiramate, valproic acid, vigabatrin and zonisamide) is discussed in relation to
      their mode of action, drug interactions and their pharmacokinetic properties. The
      review is based upon available literature data and on observations from our
      clinical practice. Up until approximately 15 years ago anti-epileptic
      therapeutics were restricted to a very few drugs that were developed in the first
      half of the 20th century. Unfortunately, many patients were refractory to these
      drugs and a new generation of drugs has been developed, mostly as add-on therapy.
      Although the efficacy of the newer drugs is no better, there is an apparent
      improvement in drug tolerance, combined with a diminished potential for adverse
      drug interactions. All new anticonvulsant drugs have undergone extensive clinical
      studies, but information on the relationship between plasma concentrations and
      effects is scarce for many of these drugs. Wide ranges in concentrations have
      been published for seizure control and toxicity. Few studies have been undertaken
      to establish the concentration-effect relationship. This review shows that TDM
      may be helpful for a number of these newer drugs.

PMID- 15576288
TI  - Pharmacogenomic genotyping methodologies.
AB  - "Personalized medicine" based on an individual's genetic makeup is slowly
      becoming a reality as pharmacogenomics moves from the research setting to the
      clinical laboratory. Concordance studies between genotype and phenotype have
      shown that inherited mutations in several key drug-metabolizing enzymes, such as
      cytochrome P450 ( CYP ) 2D6 , 2C9 , and 2C19 , result in several distinct
      phenotypes that lead to different individual responses following drug
      administration. One of the major driving forces behind pharmacogenomics and its
      ability to be used effectively are the technologies that are available. A
      beneficial genotyping test must identify most or all of the mutations that have a
      significant impact on the expression or function of drug-metabolizing enzymes,
      transporter proteins, and/or drug receptors. Selection of the appropriate
      technology will be based on several issues, including prior knowledge of the
      mutation/polymorphism, sensitivity/specificity, sample requirements, and cost.
      Since the future volume of pharmacogenomic testing is anticipated to be large,
      automation of pharmacogenomics will also become increasingly important. This
      paper provides an overview of current technologies available for assessing
      polymorphisms on a small- to large-scale basis.

PMID- 15576289
TI  - Hair analysis in toxicology.
AB  - Morphological, serological and chemical examination of human hair for medical
      purposes was initiated some decades ago. In the 1960s and 1970s, hair analysis
      was used to evaluate exposure to toxic heavy metals. At this time, examination of
      hair for organic substances, especially drugs, was not possible because
      analytical methods were not sensitive enough. Since the early 1980s, the
      development of highly sensitive and specific assay methods such as
      radioimmunoassay or gas chromatography/mass spectrometry has permitted the
      analysis of organic substances trapped in hair. This, theoretically, offered the
      possibility of revealing an individual's recent history of drug exposure
      beginning at sampling day and dating back over a period of weeks or months. The
      present review aims to summarise the various applications that have been
      published.

PMID- 15576290
TI  - Oral fluid as a diagnostic tool.
AB  - Technological advances over the past decades have enabled oral fluid to expand
      its usefulness in the diagnosis of disease, prediction of disease progression,
      monitoring of therapeutic drug levels and detection of illicit drugs. The easy
      non-invasive nature of collection and the relationship between oral fluid and
      plasma levels make oral fluid a valuable clinical tool. This review describes
      advances over the past 5 years in the area of oral fluid as a diagnostic tool,
      its use in therapeutic and illicit drug monitoring, including proposed guidelines
      for cut-off values, and methods of collection.

PMID- 15576291
TI  - Position of immunological techniques in screening in clinical toxicology.
AB  - There is a continuing increase in the use of immunological techniques in the
      field of clinical toxicology. This is primarily due to the rapidity by which
      analytical results are now required, and can be obtained, following the testing
      of individuals for drug use. There has recently been an increase in the
      repertoire of assays now available to testing laboratories (e.g., buprenorphine
      and heroin metabolite assays), with the techniques themselves becoming
      increasingly more specific for the drugs and/or metabolites being monitored
      (e.g., methadone metabolite assays). The near patient testing (NPT), or point-of
      care testing (POCT), devices are now several generations forward from their
      inception, with some tests now approaching the sensitivity and specificity of
      automated laboratory-based methods. This review has been collated from the
      literature to illustrate some of the possible reasons for the move towards the
      increasing use of immunological techniques, and to highlight some of the
      advantages and disadvantages associated with such drug screening methods. In
      particular, it has been shown that it is important to determine, monitor and
      review the knowledge and training of the individual using the technique. In
      addition, quality control and quality assessment are paramount to ensure the
      validity of any drug testing being performed. It has also been shown that it is
      vital to maintain and develop the relationships between the staff performing the
      testing, the laboratory (if the testing is performed using NPT devices), and the
      clinicians utilising the results obtained from drug testing. Without these links,
      interpretive errors could arise which could adversely affect the diagnosis and
      management of patients.

PMID- 15576292
TI  - Position of chromatographic techniques in screening for detection of drugs or
      poisons in clinical and forensic toxicology and/or doping control.
AB  - This paper reviews chromatographic screening procedures for simultaneous
      detection of several drug classes relevant to clinical and forensic toxicology or
      doping control in urine or blood using gas chromatography-mass spectrometry (GC
      MS), liquid chromatography coupled with a diode-array detector (LC-DAD) or a mass
      spectrometer (LC-MS). The pros and cons of the different techniques and
      procedures are discussed leading to the following conclusions and perspectives.
      GC-MS, especially in the electron ionization full-scan mode, is still the method
      of choice for comprehensive screening providing best separation power,
      specificity and universality, although requiring derivatization. LC-DAD is also
      often used for screening, but its separation power and its specificity are still
      inferior to those of GC-MS. Finally, LC-MS has shown to be an ideal supplement,
      especially for the detection of more polar, thermolabile and/or low-dose drugs,
      especially in blood plasma. It may become the gold standard in clinical and
      forensic toxicology and doping control if, at a later date, the costs of the
      apparatus will be markedly reduced, the current disadvantages like
      irreproducibility of fragmentation, reduction of ionization by matrix, etc. will
      be overcome, and finally if one of the increasing number of quite different
      techniques will become the apparatus standard.

PMID- 15576293
TI  - Systematic toxicological analysis by high-performance liquid chromatography with
      diode array detection (HPLC-DAD).
AB  - In recent years, photodiode array detectors (DADs) have been much improved with
      respect to wavelength accuracy and resolution, sensitivity, linearity and
      software operation. UV spectra of drugs measured with up-to-date DADs from
      different manufacturers are in excellent agreement, have the same quality as
      measured by a conventional UV spectrometer and are highly reproducible. The
      calculation of similarity parameters by the DAD software includes the entire
      range of the spectra compared and allows recognition of very small differences.
      It was shown in a systematic study of more than 2500 toxicologically relevant
      substances that UV spectra have a very high specificity with respect to substance
      structure. Therefore, HPLC-DAD in combination with a comprehensive database of UV
      spectra and retention parameters is one of the most efficient techniques used in
      systematic toxicological analysis (STA). Furthermore, the method is advantageous
      for the identification of metabolites, since in many cases they have the same or
      very similar UV spectra compared with their respective parent substances and
      their retention times on reversed-phase columns are shifted in a manner typical
      of the particular biotransformation reaction. Beside these general aspects,
      practical applications of HPLC-DAD for STA are reviewed with respect to sample
      preparation and chromatographic conditions. The efficiency of the method is
      demonstrated for an example of a routine procedure using liquid-liquid extraction
      with CH 2 Cl 2 and protein precipitation for sample preparation, a system of
      three isocratic mobile phases with different acetonitrile/phosphate buffer ratios
      and RP8 columns for chromatography and a database of 2682 UV spectra and relative
      retention times for substance identification.

PMID- 15576294
TI  - Analysis of gamma-hydroxybutyric acid, DL-lactic acid, glycolic acid, ethylene
      glycol and other glycols in body fluids by a direct injection gas chromatography
      mass spectrometry assay for wide use.
AB  - Analysis of blood of severely intoxicated patients always requires prompt
      investigation. Diagnosis of intoxication with ethylene glycol, gamma
      hydroxybutyric acid or D-lactic acid takes hours, since several different
      procedures are required. Rapid derivatization of the common hydroxyl function may
      resolve this analytical problem. Here we describe a fast method for the
      simultaneous measurement of ethylene glycol, glycolic acid, gamma-hydroxybutyric
      acid and racemic lactic acid. Only 20 microl of serum, plasma or urine are
      required for immediate derivatization at 70 degrees C with 750 microl of bis-N,O
      trimethylsilyl trifluoroacetamide after adding 20 microl of internal standard
      solution (1,3-propylene glycol) and 20 microl of the catalyst dimethylformamide.
      After centrifugation an aliquot is transferred to a gas chromatographic system
      and analyzed with electron-impact mass spectrometry in selective ion monitoring
      mode. The derivatized acids and ethylene glycol are well separated and detected
      with a limit of detection ranging from 0.12 mg/l for ethylene glycol to 0.95 mg/l
      for gamma-hydroxybutyric acid, while the limit of quantification ranged from 0.4
      mg/l for ethylene glycol to 3.15 mg/l for gamma-hydroxybutyric acid. The method
      is linear from 0.5 to 1800 mg/l blood for ethylene glycol, from 0.7 to 1200 mg/l
      for lactic acid, from 1.2 to 1800 mg/l for glycolic acid, and from 3.2 to 200
      mg/l for gamma-hydroxybutyric acid, with analytical recoveries, accuracy, day-to
      day and within-day precision well within the required limits. Total analysis time
      with one calibrator was 30 min, derivatization time included. This method is very
      suitable for emergency toxicology, since several toxic substances can be
      quantified simultaneously in a fast and sensitive manner.

PMID- 15576295
TI  - Hematopoietic cytokines as tumor markers.
AB  - Stem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony
      stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and
      macrophage-colony stimulating factor (M-CSF) are members of a group of
      glycoproteins called hematopoietic cytokines (HCs). These cytokines regulate the
      growth and differentiation of hematopoietic progenitor cells and functionally
      activate mature neutrophils or macrophages. The effect of HCs is not limited to
      bone marrow cells. Some studies have shown that HCs can also stimulate the
      proliferation of non-hematopoietic cells. The receptors for HCs have been
      detected in cancer cell lines, and stimulation of HCs receptors induced
      proliferation of tumor cells. Moreover, some investigations have shown HC mRNA
      expression in these cell lines and recent studies have demonstrated that HCs can
      stimulate tumor progression. Several cells of malignant tumors have been observed
      to secrete large amounts of HCs and increased concentrations of HCs have been
      found in the sera of cancer patients. There are a number of situations in which
      the measurement of HCs may provide clinically useful information, particularly
      regarding prognosis and response to treatment. In this paper we discuss the
      results of studies that have examined the potential use of HCs as tumor markers.

PMID- 15576296
TI  - The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the
      balance between plasma proatherogenic and antiatherogenic lipoproteins and to
      predict coronary risk.
AB  - BACKGROUND: The apolipoprotein B (apoB)/apoA-I ratio represents the balance of
      proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to
      determine whether the apoB/apoA-I ratio was superior to any of the cholesterol
      ratios - total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low
      density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C - in predicting
      the risk of coronary disease. Moreover, we examined whether any lipids,
      lipoproteins or cholesterol ratios add significant predictive information beyond
      that provided by the apoB/apoA-I ratio. METHODS: Plasma lipids, lipoproteins,
      apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40 years of
      age. After a mean follow-up of 98 months, 1183 men and 560 women had died from a
      myocardial infarction in this prospective apolipoprotein-related mortality risk
      (AMORIS) study. RESULTS: High apoB and a high apoB/apoA-I ratio were strongly
      related to increased coronary risk, while high apoA-I was inversely related to
      risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in
      predicting risk. This advantage was most pronounced in subjects with LDL-C levels
      <3.6 mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to
      apoB/apoA-I in risk models did not further improve the strong predictive value of
      apoB/apoA-I. CONCLUSIONS: These results indicate that the apoB/apoA-I ratio is at
      present the best single lipoprotein-related variable to quantitate coronary risk.
      Given the additional advantages apolipoproteins possess - fasting samples are not
      required, apoB/apoA-I is a better index of the adequacy of statin therapy than
      LDL-C, and the measurement of apoB and apoA-I are standardized, whereas LDL-C and
      HDL-C are not - there would appear to be considerable advantage to integrating
      apolipoproteins into clinical practice.

PMID- 15576297
TI  - Rapid combined genotyping of factor V, prothrombin and methylenetetrahydrofolate
      reductase single nucleotide polymorphisms using minor groove binding DNA
      oligonucleotides (MGB probes) and real-time polymerase chain reaction.
AB  - Risk factors for cardiovascular diseases and venous thromboembolism involve both
      acquired and hereditary conditions. Among the latter, mutations in genes coding
      for coagulation factors (factor V Leiden [Arg506Gly], G20210A in the 3'
      untranslated region of factor II ) and variant C677T of the
      methylenetetrahydrofolate reductase (MTHFR ) are often involved and co-inherited.
      These three factors were genotyped simultaneously in the same 96-well plate,
      using a real-time polymerase chain reaction (PCR) Taqman assay and minor groove
      binding DNA oligonucleotides (MGB probes). While primers and MGB probes matched
      their corresponding single nucleotide polymorphism (SNP), the real-time MGB
      program was identical for each target gene. Homozygous wild-type (WT; -/-),
      heterozygous (+/-) or homozygous (+/+) variants (n = 362) were selected for
      factor V (n = 115, with -/-, 40; +/-, 40; +/+, 35), factor II (n = 122, with -/-,
      60; +/-, 60; +/+, 2), and MTHFR (n = 120, with -/-, 40; +/-, 40; +/+, 40),
      according to the results of conventional PCR-restriction fragment length
      polymorphism (PCR-RFLP), but the allelic discrimination was performed blind.
      Results of the real-time MGB and PCR-RFLP assays were identical. This new assay
      was easy and fast with high throughput, without risk of molecular carryover, and
      cost-effective for laboratories utilizing the Taqman or related fluorescence
      reading methods. These advantages make it particularly suitable for large-scale
      combined genotyping of several polymorphisms in the routine setting.

PMID- 15576298
TI  - Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic
      stroke.
AB  - The 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene 677C --> T
      polymorphism causes an A222V amino acid change which affects MTHFR enzyme
      activity and can increase homocysteine, a vascular disease risk factor. This
      polymorphism was examined for association with stroke. In a case-control study of
      241 ischemic stroke patients and 304 controls in Hong Kong, the V allele
      increased in stroke [28% vs. 20%, odds ratio (OR) 1.5, p=0.003]. A lack of
      significance for the increase in the VV genotype (7.5% vs. 4.6%, OR 1.7, p =
      0.16) may be due to its rarity in this region. V -allele carriers had more severe
      strokes (according to the NIH stroke scale). The association of the V allele with
      stroke occurred mostly in women or older subjects and was due to decreasing V
      allele frequency with age, as seen in other studies. This V frequency decline
      with age might be due to a loss of V -carrying controls from a higher risk of
      cancer, vascular disease, bone fracture, and kidney failure when folate is
      sparse. Examination of previous studies revealed that the association of VV
      genotype with stroke appeared stronger in Japan than elsewhere, possibly due to
      dietary differences. Perhaps folate supplementation for stroke prevention would
      particularly benefit VV individuals in such high-risk regions.

PMID- 15576300
TI  - The assessment of bone metabolism in female elite endurance athletes by
      biochemical bone markers.
AB  - PURPOSE: Premature osteoporosis is a frequent problem in female athletes. Current
      concepts suggest that a disruption of the hypothalamic-pituitary axis leads to
      hypoestrogenism, which then causes amenorrhea and osteoporosis. However, the
      underlying mechanisms have been insufficiently investigated. Osteoprotegerin
      (OPG) and soluble TNF-alpha receptor antagonist ligand (sRANKL) regulate the
      balance of osteoblasts and osteoclasts. Their role in the pathogenesis of
      osteoporosis in female athletes has not been studied yet. METHODS: We measured
      OPG and sRANKL in relation to biochemical bone markers [osteocalcin (OC), bone
      alkaline phosphatase (BAP), serum beta-crosslaps (CTx)] and female sex hormones
      [estradiol (E2) and luteinizing hormone (LH)] in fastening blood samples from 25
      female elite endurance athletes and 25 matched controls. RESULTS: Athletes
      exhibited significantly higher levels of the bone resorption marker CTx than
      controls (0.61 +/- 0.26 vs. 0.44 +/- 0.15 ng/ml). OPG and sRANKL were not
      changed. Subgroup analysis revealed that athletes using oral contraceptives [A
      OCC(-)] had significantly higher levels of CTx (0.82 +/- 0.20 vs. 0.50 +/- 0.14
      ng/ml), BAP [37.3 (23.2-54.4) U/l vs. 25.2 (20.3-35.6) U/l] and OPG (3.4+/-0.8
      vs. 2.7+/-0.8 ng/ml) than controls who did not use oral contraceptives [C-OCC(
      )]. While the difference for CTx exceeded the least significant change in this
      marker by approximately 30%, the differences for the bone formation markers OC
      and BAP were close to the least significant change. In athletes using oral
      contraceptives [A-OCC(+)] we found no differences compared to controls.
      CONCLUSIONS: A-OCC(-) athletes have increased bone turnover with a particular
      stimulation of bone resorption. The increased bone resorption is not accompanied
      by a shift of the OPG/sRANKL relationship towards an osteoclastogenic
      constellation. Since increased bone resorption was not detectable in A-OCC(+)
      athletes, it can be suggested that OCC use might protect bone health in female
      athletes.

PMID- 15576299
TI  - Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of
      nitric oxide synthase (NOS). Elevated ADMA plasma levels have been reported in
      connection with diseases associated with an impaired endothelial L-arginine-NO
      pathway and endothelial dysfunction, such as atherosclerosis,
      hypercholesterolemia, chronic heart failure, diabetes mellitus, and hypertension.
      NO production by NOS is decreased due to elevated ADMA levels. In fact, there is
      increasing interest in determination of ADMA levels in samples of various
      origins. The aim of this work was to develop a precise and easy immunoassay in
      contrast to the existing methods, such as HPLC, liquid chromatography-mass
      spectrometry (LC-MS) and gas chromatography (GC)-MS. We determined cross
      reactivity in our immunoassay of 1.2% for symmetric dimethylarginine and <0.02%
      for L-arginine. The limit of quantitation was 0.05 micromol/l. We found good
      correlation of the values measured when we compared our assay with LC-tandem MS
      (n = 29; r = 0.984; p < 0.0001). We determined ADMA levels in human serum and
      plasma, mouse and rat plasma, and cell culture supernatant. For human plasma we
      found a mean of 0.65 micromol/l in healthy subjects. In the plasma of mice and
      rats we found mean concentrations of 1.05 and 1.09 micromol/l, respectively.

PMID- 15576301
TI  - Declines in serum free and bound choline concentrations in humans after three
      different types of major surgery.
AB  - We examined the changes in circulating choline status in humans in response to
      major surgery by measuring serum free and phospholipid-bound choline
      concentrations before, during and 1-72 h after total abdominal hysterectomy, off
      pump coronary artery graft surgery or brain tumor surgery. Preoperatively, the
      mean serum free and phospholipid-bound choline concentrations in patients
      scheduled for abdominal hysterectomy (n = 26), off-pump coronary artery grafting
      surgery (n = 34) or brain tumor surgery (n = 24) were 12.3 +/- 0.5, 12.1 +/- 0.4
      and 11.4 +/- 0.4 micromol/l, and 2495 +/- 75, 2590 +/- 115 and 2625 +/- 80
      micromol/l, respectively. Serum free choline and phospholipid-bound choline
      concentrations decreased from these baseline values to 8.8 +/- 0.7 (p < 0.001),
      8.8 +/- 0.5 (p < 0.001) and 8.2 +/- 0.4 micromol/l (p < 0.001), and 2050 +/- 108
      (p < 0.001), 2166 +/- 59 (p < 0.001) and 1884 +/- 104 micromol/l (p < 0.001) at 1
      h after hysterectomy, off-pump bypass graft surgery or brain tumor surgery,
      respectively. They remained at these low levels for 24 h and then gradually
      increased towards the preoperative values at 48-72 h postoperatively. Serum
      cortisol increased postoperatively in all surgical patients for 24 h and its
      levels were inversely correlated with serum free and bound choline
      concentrations. These results show that circulating free and bound choline
      concentrations decrease for 72 h after total abdominal hysterectomy, off-pump
      coronary artery graft surgery or brain tumor surgery in humans.

PMID- 15576302
TI  - Analysis of inflammatory response in human plasma samples by an automated
      multicapillary electrophoresis system.
AB  - A new automated multicapillary zone electrophoresis instrument with a new high
      resolution (HR) buffer (Capillarys with HR buffer) for analysis of human plasma
      proteins was evaluated. Albumin, alpha(1)-antitrypsin, alpha(1)-acid
      glycoprotein, haptoglobin, fibrinogen, immunoglobulin (Ig)A, IgG and IgM were
      determined nephelometrically in 200 patient plasma samples. The same samples were
      then analyzed on the Capillarys system (Sebia, Paris, France). The albumin
      concentration from the nephelometric determination was used for quantification of
      the individual peaks in the capillary electrophoresis (CE) electropherogram.
      There was strong linear correlation between the nephelometric and electrophoretic
      determination of alpha(1)-antitrypsin (R(2) = 0.906), alpha(1)-acid glycoprotein
      (R(2) =0.894) and haptoglobin (R(2) = 0.913). There was also good correlation
      between the two determinations of gamma-globulins (R(2) = 0.883), while the
      correlation was weaker for fibrinogen (R(2) = 0.377). The Capillarys instrument
      is a reliable system for plasma protein analysis, combining the advantages of
      full automation, good analytical performance and high throughput. The HR buffer
      in combination with albumin quantification allows the simultaneous quantification
      of inflammatory markers in plasma samples without the need for nephelometric
      determination of these proteins.

PMID- 15576303
TI  - Multicenter evaluation of the commutability of a potential reference material for
      harmonization of enzyme activities.
AB  - Standardization of laboratory results allows for the use of common reference
      intervals and can be achieved via calibration of field methods with secondary
      reference materials. These harmonization materials should be commutable, i.e.,
      they produce identical numerical results independent of assay principle or
      platform. This study assessed the commutability of a cryolyoprotectant-containing
      harmonization material, obtained from the Dutch Foundation for Quality Assessment
      in Clinical Laboratories, that is intended to harmonize measurements of enzyme
      activities within the Dutch project "Calibration 2000". The catalytic
      concentrations of alkaline phosphatase, aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase and creatine
      kinase were analyzed in pooled patient sera and in the reference material in 14
      laboratories. On liquid chemistry analyzers the harmonization material behaves
      like patient material. The enzyme activities measured in it fall on the
      regression lines calculated from activities measured in serum samples. For dry
      chemistry analyzers the activities of all enzymes measured in the harmonizator
      differ from the serum-based regression line. We show that this is due to the
      sucrose-containing cryolyoprotectant in the harmonization material. For each
      enzyme, correction factors were calculated that compensated for the bias and
      proved to be constant between reagent lots. Depending on the enzyme activity
      measured, application of these factors leads to 2- to 10-fold reduction of
      between-laboratory percentage coefficient of variation. Thus, additives to
      (potential) reference materials may alter their matrix in a way that interferes
      with analysis on certain test systems. The bias caused may be quantifiable and
      correctable. Establishment of correction factors leads to analytical
      uncertainties and costs. Therefore, matrix-based materials without additives
      should be selected as reference materials.

PMID- 15576304
TI  - HDL and clinical and biochemical correlates in Italian non-smoker women.
AB  - High-density lipoprotein (HDL)-cholesterol levels, inversely related to the risk
      of myocardial infarction, are determined by genetic and environmental factors.
      The aim of this study was to evaluate the prevalence of low and high HDL plasma
      levels and the influence of environmental factors and lipid profile in an Italian
      non-smoker female population. HDL, apolipoprotein A-I, apolipoproteins, lipids
      and estrogen plasma levels were measured in a population of 1471 women with a
      mean age of 45 +/- 14 years. HDL values < or = 35 mg/dl were noted in 11.2% of
      the subjects, showing 2.4% coronary heart disease (CHD) prevalence. The 90th
      percentile was characterized by HDL levels > or = 66 mg/dl and the absence of
      coronary atherosclerosis. Total cholesterol, apolipoprotein B and triglycerides
      (r = -0.31, p < 0.0001) were the main determinants of HDL levels; apolipoprotein
      E, estrogen use, body mass index (BMI), alcohol consumption and age showed a
      weaker correlation. Apolipoprotein A-I concentration was influenced more notably
      by estrogen use, total cholesterol and apolipoprotein E; levels of triglycerides,
      apolipoprotein B, BMI, age and alcohol consumption are less important. The
      parameters considered here, taken together, explain HDL and apolipoprotein A-I
      variability of approximately 31% and 24%, respectively. A surprisingly high
      prevalence of very low (< or = 35 mg/dl) and high (> or = 66 mg/dl) HDL levels in
      Italian women further confirms the importance of studies on the HDL distribution
      in different population groups.

PMID- 15576305
TI  - Hyperhomocysteinaemia is associated with uveitis but not with deep venous
      thrombosis in Behcet's disease.
AB  - Plasma homocysteine was assessed in Behcet's disease (BD) patients in order to
      determine the prevalence of hyperhomocysteinaemia in BD and to test its
      association with clinical manifestations of the disease. The study included 59
      patients with BD and 118 age- and sex-matched healthy subjects. Plasma
      homocysteine, vitamin B(12) and folate were assessed by automated immunoassay
      methods. Hyperhomo-cysteinaemia was defined as plasma homocysteine >15
      micromol/l. Plasma homocysteine concentrations and the prevalence of
      hyperhomocysteinaemia were significantly higher in BD patients than in controls
      [median (5th-95th percentile), 11.3 (6.6-28.1) vs. 10.6 (6.6-17.1) micromol/l,
      and 25.4% vs. 9.3%, respectively]. In BD patients, hyperhomocysteinaemia was
      related to male gender, disease severity and uveitis [odds ratio (OR), 5.32; 95%
      confidence interval (CI), 1.43-21.61; p = 0.008], but not to age, smoking,
      disease activity, deep venous thrombosis, arthritis or neurological involvement.
      The association between uveitis and hyperhomocysteinaemia persisted (multi
      adjusted OR, 7.46; 95% CI, 1.03-54.3; p = 0.05) after adjusting for gender, age,
      disease activity and duration, smoking, deep venous thrombosis, and serum
      concentrations of creatinine, vitamin B(12) and folate. Plasma homocysteine
      should be measured in patients with BD, and the effect of B-vitamin
      supplementation should be tested in those with hyperhomo-cysteinaemia.

PMID- 15576306
TI  - Production of gender-specific morning salivary cortisol reference intervals using
      internationally accepted procedures.
AB  - BACKGROUND: Salivary cortisol concentrations correlate well with biologically
      active unbound free plasma cortisol concentrations. Despite its practical and
      analytical advantages, salivary cortisol measurement has been used mainly as a
      research tool rather than for the routine evaluation of adrenal function. This
      may be partly explained by the lack of robust reference data in the literature.
      METHODS: Using the recommended procedures for the production of reference
      intervals published by the International Federation of Clinical Chemistry, we
      aimed to produce morning salivary cortisol reference intervals for males and
      females. Salivary cortisol was measured in 496 specimens collected from 248
      reference individuals (128 males, median age 41 years, range 16-86; and 120
      females, median age 44 years, range 16-98) attending an otorhinolaryngology
      clinic. Reference individuals mailed saliva specimens sampled on two consecutive
      mornings to our laboratory, where cortisol concentrations were measured. RESULTS:
      Statistical analysis showed no significant correlation with age or body mass
      index. The following 95% gender-partitioned reference intervals were produced:
      males 10.9-40.3 nmol/l; and females 9.3-40.3 nmol/l. CONCLUSION: Knowledge of
      these salivary cortisol reference intervals helps us monitor the adrenal function
      of outpatients using topical intranasal glucocorticoids for rhinosinusitis.

PMID- 15576307
TI  - Concentrations of N-terminal pro-brain natriuretic peptide and troponin T in
      plasma of 75-year-old apparently healthy persons.
AB  - Clinical chemical reference values for older persons are sparse and mostly
      intermixed with those for younger persons. We had a unique opportunity to obtain
      blood samples from volunteers who were 75 years old and living in two districts
      of Vienna, Austria. Consequently, we utilized stored plasma samples to obtain
      reference intervals for 120 apparently healthy 75-year-old participants for pro
      brain natriuretic peptide (proBNP), as well as for troponin T. The N-terminal
      (NT)-proBNP protein assay is currently used as a diagnostic and prognostic aid in
      patients with heart failure and as a prognostic marker in acute coronary
      syndromes. Specifically, the concentration of NT-proBNP in serum or plasma aids
      in the prognosis of ventricular systolic dysfunction and helps to differentiate
      between cardiac and non-cardiac causes. The median NT-proBNP plasma value for men
      and women in our cohort was calculated as 98 pg/ml, comparing favorably with
      reported values, in that a NT-proBNP concentration less than 100 pg/ml excludes
      acutely decompensated heart failure. Our calculated 97.5 percentile was slightly
      higher (359 pg/ml) than the 97.5 percentile in a group of 50-65-year-old persons
      (198 and 222 pg/ml for men and women, respectively) revealing the influence of
      age on this parameter. Because of its high tissue-specificity, cardiac troponin T
      is a cardiospecific, highly sensitive marker for myocardial damage. However, the
      troponin T concentrations in the plasma specimens from this cohort were all below
      the detection limit of 0.01 ng/ml, preventing any further data handling.

PMID- 15576308
TI  - External quality assessment for biochemical markers of myocardial damage: an
      Italian experience.
AB  - In 1999 the Centre of Biomedical Research (CRB) in co-operation with the Italian
      interdisciplinary and intersociety Working Group on Markers of Myocardial Damage
      proposed a national external quality assurance scheme that was granted in
      accordance with the UK Clinical Pathology Accreditation Standards in 2001. The
      scheme, which stresses the importance of educational aspects in quality
      assurance, was scientifically designed to ensure that it would provide an
      objective assessment of participants' performance and promote quality
      improvements to meet the needs of participants. The present paper reports on the
      data collected in EQA cycles conducted to evaluate improvements in the
      performance of participants and in related methods. The findings obtained
      demonstrate that during the 4-year experience the scheme provided opportunities
      to improve the performance of laboratories and promoted an efficient, more
      satisfactory approach to analytical aspects. The number of unacceptable
      performances decreased from 11.6% to 5.6% for troponin I, from 19.5% to 9.0% for
      myoglobin and from 13.2% to 4.3% for creatine kinase myocardial isoenzyme (CK
      MB). During cycles in 2001 and 2002, inter-variability (coefficient of variation,
      CV%) data for all markers appeared satisfactory and showed a significant
      improvement (lower than 10%), in particular for procedures automated on Dade
      Behring Dimension and Beckman Access systems. However, reference
      values/decisional limits declared by laboratories and those suggested by the
      manufacturers are not comparable, even within the same diagnostic system. The
      findings demonstrate that participation in EQA schemes provided an opportunity
      for participating laboratories to continuously improve the quality of their
      services.

PMID- 15576309
TI  - Further evaluation of the immunonephelometric assay of soluble transferrin
      receptor and assessment of pediatric values in southern Italy.

PMID- 15576310
TI  - Exercise raises serum heat-shock protein 70 (Hsp70) levels.

PMID- 15576311
TI  - Hepatitis C-associated complement cold activation.

PMID- 15576312
TI  - The relationship between cryoglobulins and HCV-RNA in the serum of patients
      infected with different HCV genotypes.

PMID- 15576313
TI  - Artificial neural network-based algorithm for the evaluation of serum protein
      capillary electrophoresis.

PMID- 15576314
TI  - State-of-the-art systematic error for therapeutic drug monitoring.

PMID- 15576315
TI  - Peculiarities and problems with the EXCEL F-test.

PMID- 15576316
TI  - Questionable results - should EQA results be accepted as submitted or should
      'obvious mistakes' be corrected? Reply to Wood WG. Questionable results - who
      directs the EQAS organisers? CCLM 2004;42(9):1073.

PMID- 15576318
TI  - Activation of the kallikrein-kinin system and release of new kinins through
      alternative cleavage of kininogens by microbial and human cell proteinases.
AB  - Kinins are released from kininogens through the activation of the Hageman factor
      prekallikrein system or by tissue kallikrein. These peptides exert various
      biological activities, such as vascular permeability increase, smooth muscle
      contraction, pain sensation and induction of hypotension. In many instances
      kinins are thought to be involved in the pathophysiology of various diseases.
      Recent studies have revealed that microbial and human cell proteinases activate
      Hageman factor and/or prekallikrein, or directly release kinin from kininogens.
      This review discusses the activation of the kinin-release system by mast-cell
      tryptase and microbial proteinases, including gingipains, which are cysteine
      proteinases from Porphyromonas gingivalis , the major pathogen of periodontal
      disease. Each enzyme is evaluated in the context of its association to allergy
      and infectious diseases, respectively. Furthermore, a novel system of kinin
      generation directly from kininogens by the concerted action of two proteinases is
      described. An interesting example of this system with implications to bacterial
      pathogenicity is the release of kinins from kininogens by neutrophil elastase and
      a synergistic action of cysteine proteinases from Staphylococcus aureus . This
      alternative production of kinins by proteinases present in diseased sites
      indicates a significant contribution of proteinases other than kallikreins in
      kinin generation. Therefore kinin receptor antagonists and proteinase inhibitors
      may be useful as therapeutic agents.

PMID- 15576319
TI  - Molecular mechanism for activation and regulation of matrix metalloproteinases
      during bacterial infections and respiratory inflammation.
AB  - Matrix metalloproteinases (MMPs) are critical mediators of tissue remodeling.
      Inappropriate regulation of MMPs causes many pathological events, including
      microbial invasion and inflammatory tissue damage. Some of the bacterial
      exoproteinases can effectively activate pro-MMPs (inactive zymogens) via limited
      proteolysis around their autoinhibitory domains. In addition, overproduction of
      nitric oxide (NO) may contribute to respiratory inflammation via the formation of
      reactive nitrogen species (RNS). Several studies have identified regulatory
      properties of NO/RNS on biomolecules due to functional modification of their
      cysteine residues. In fact, NO/RNS can mediate activation and expression of MMPs,
      because RNS can interact with a cysteine switch in the autoinhibitory domain,
      thus converting proMMPs into their active forms without proteolysis. Many studies
      have indicated that NO/RNS can participate in expression of various genes that
      affect immune-inflammatory responses, including MMPs. Although NO in some cases
      upregulates MMPs, S -nitrosothiols downregulate MMP-9 expression by suppressing
      the NF-kappaB pathway. While microbial proteinases cause excessive activation of
      MMPs and contribute to microbial pathogenesis, NO/RNS may modulate expression and
      activation of MMPs as well as various inflammatory mediators, depending on the
      redox status at sites of inflammation. Therefore, appropriate regulation of MMPs
      may be of potential therapeutic value for various infections and inflammatory
      lung diseases.

PMID- 15576320
TI  - Role of bacterial proteases in pseudomonal and serratial keratitis.
AB  - Pseudomonas aeruginosa and Serratia marcescens can cause refractory keratitis
      resulting in corneal perforation and blindness. These bacteria produce various
      kinds of proteases. In addition to pseudomonal elastase (LasB) and alkaline
      protease, LasA protease and protease IV have recently been found to be more
      important virulence factors of P. aeruginosa . S. marcescens produces a cysteine
      protease in addition to metalloproteases. These bacterial proteases have a number
      of biological activities, such as degradation of tissue constituents and host
      defense-oriented proteins, as well as activation of zymogens (Hageman factor,
      prekallikrein and pro-matrix metalloproteinases) through limited proteolysis. In
      this article, the properties of these bacterial proteases are reviewed and the
      pathogenic roles of these proteases in pseudomonal keratitis are discussed.

PMID- 15576321
TI  - Cysteine cathepsins in human cancer.
AB  - Proteases play causal roles in the malignant progression of human tumors. This
      review centers on the roles in this process of cysteine cathepsins, i.e.,
      peptidases belonging to the papain family (C1) of the CA clan of cysteine
      proteases. Cysteine cathepsins, most likely along with matrix metalloproteases
      (MMPs) and serine proteases, degrade the extracellular matrix, thereby
      facilitating growth and invasion into surrounding tissue and vasculature. Studies
      on tumor tissues and cell lines have shown changes in expression, activity and
      distribution of cysteine cathepsins in numerous human cancers. Molecular,
      immunologic and pharmacological strategies to modulate expression and activity of
      cysteine cathepsins have provided evidence for a causal role for these enzymes in
      tumor progression and invasion. Clinically, the levels, activities and
      localization of cysteine cathepsins and their endogenous inhibitors have been
      shown to be of diagnostic and prognostic value. Understanding the roles that
      cysteine proteases play in cancer could lead to the development of more
      efficacious therapies.

PMID- 15576322
TI  - Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal
      defenses against influenza A virus infection in the airway and chemical agents up
      regulating their levels may have therapeutic potential.
AB  - Influenza A virus (IAV) is one of the most common infectious pathogens in humans.
      Entry of this virus into cells is primarily determined by host cellular trypsin
      type processing proteases, which proteolytically activate viral membrane fusion
      glycoprotein precursors. Human IAV and murine parainfluenza virus type 1 Sendai
      virus are exclusively pneumotropic, and the infectious organ tropism of these
      viruses is determined by the susceptibility of the viral envelope glycoprotein to
      cleavage by proteases in the airway. Proteases in the upper respiratory tract are
      suppressed by secretory leukoprotease inhibitor, and those in the lower
      respiratory tract are suppressed by pulmonary surfactant, which by adsorption
      inhibits the interaction between the proteases and viral membrane proteins.
      Although the protease activities are predominant over the activities of
      inhibitory compounds under normal airway conditions, intranasal administration of
      inhibitors was able to significantly suppress multi-cycles of viral replication
      in the airway. In addition, we identified chemical agents that could act as
      defensive factors by up-regulating the levels of the natural inhibitors and
      immunoglobulin A (IgA) in airway fluids. One of these compounds, ambroxol, is a
      mucolytic and anti-oxidant agent that stimulates the release of secretory
      leukoprotease inhibitor and pulmonary surfactant in the early phase, and IgA in
      the late phase of infection at an optimal dose, i.e. a dose sufficient to inhibit
      virus proliferation and increase the survival rate of animals after treatment
      with a lethal dose of IAV. Another agent, clarithromycin, is a macrolide
      antibiotic that increases IgA levels through augmentation of interleukin-12
      levels and mucosal immunization in the airway. In addition to the sialidase
      inhibitors, which prevent the release of IAV from infected cells, inhibitors of
      the processing proteases and chemical agents that augment mucosal immunity and/or
      levels of the relevant defensive compounds may also ultimately prove to be useful
      as new anti-influenza agents.

PMID- 15576323
TI  - Design of inhibitors against HIV, HTLV-I, and Plasmodium falciparum aspartic
      proteases.
AB  - Aspartic proteases have emerged as targets for substrate-based inhibitor design
      due to their vital roles in the life cycles of the organisms that cause AIDS,
      malaria, leukemia, and other infectious diseases. Based on the concept of
      mimicking the substrate transition-state, we designed and synthesized a novel
      class of aspartic protease inhibitors containing the hydroxymethylcarbonyl (HMC)
      isostere. An unnatural amino acid, allophenylnorstatine [Apns; (2 S ,3 S )-3
      amino-2-hydroxy-4-phenylbutyric acid], was incorporated at the P1 site in a
      series of peptidomimetic compounds that mimic the natural substrates of the HIV,
      HTLV-I, and malarial aspartic proteases. From extensive structure-activity
      relationship studies, we were able to identify a series of highly potent
      peptidomimetic inhibitors of HIV protease. One highly potent inhibitor of the
      malarial aspartic protease (plasmepsin II) was identified. Finally, a promising
      lead compound against the HTLV-I protease was identified.

PMID- 15576324
TI  - Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis:
      identification of its responsible molecules in translation products of rgpA, kgp,
      and hagA genes.
AB  - Arg- (Rgp) and Lys-gingipains (Kgp) are two individual cysteine proteinases
      produced by Porphyromonas gingivalis , an oral anaerobic bacterium, and are
      implicated as major virulence factors in a wide range of pathologies of adult
      periodontitis. Coaggregation of this bacterium with other oral bacteria is an
      initial and critical step in infectious processes, yet the factors and mechanisms
      responsible for this process remain elusive. Here we show that the initial
      translation products of the rgpA , kgp and hemagglutinin hagA genes are
      responsible for coaggregation of P. gingivalis and that the proteolytic activity
      of Rgp and Kgp is indispensable in this process. The rgpA rgpB kgp- and rgpA kgp
      hagA -deficient triple mutants exhibited no coaggregation activity with
      Actinomyces viscosus , whereas the kgp -null and rgpA rgpB -deficient double
      mutants significantly retained this activity. Consistently, the combined action
      of Rgp- and Kgp-specific inhibitors strongly inhibited the coaggregation activity
      of the bacterium, although single use of Rgp- or Kgp-specific inhibitor
      significantly retained this activity. We also demonstrate that the 47- and 43-kDa
      proteins produced from the translation products of the rgpA , kgp , and hagA
      genes by proteolytic activity of both Rgp and Kgp are responsible for the
      coaggregation of P. gingivalis.

PMID- 15576325
TI  - Coordinate expression of the Porphyromonas gingivalis lysine-specific gingipain
      proteinase, Kgp, arginine-specific gingipain proteinase, RgpA, and the
      heme/hemoglobin receptor, HmuR.
AB  - Heme utilization in Porphyromonas gingivalis requires the participation of an
      outer membrane hemin/hemoglobin receptor, HmuR, the lysine-specific gingipain
      proteinase (Kgp) and arginine-specific gingipain proteinase (Rgp). In this study,
      the expression of hmuR , kgp and rgpA genes in response to growth with different
      heme sources was examined by reverse transcription-polymerase chain reaction and
      enzyme-linked immunoassay. Coordinate regulation of hmuR , kgp and rgpA gene
      expression was evaluated through utilization of P. gingivalis hmuR and kgp
      mutants or by selective inactivation of proteinases with Kgp- and Rgp-specific
      inhibitors. We observed that expression of the kgp and rgpA genes was not tightly
      regulated by heme, but rather by the growth phase. In contrast, expression of the
      hmuR gene was negatively regulated by heme, while growth of P. gingivalis with
      human serum resulted in increased hmuR expression. A P. gingivalis kgp isogenic
      mutant demonstrated significantly increased hmuR gene expression, and
      inactivation of Kgp and Rgp activity by specific inhibitors up-regulated hmuR
      gene transcription. Moreover, inactivation of Kgp up-regulated rgpA
      transcription. Finally, a P. gingivalis hmuR mutant exhibited repressed kgp gene
      expression and lysine-specific proteinase activity. Collectively, these results
      indicate that kgp , rgpA and hmuR gene transcription is coordinately regulated
      and may facilitate greater efficiency of heme utilization in P. gingivalis .

PMID- 15576326
TI  - Genetic characterization of staphopain genes in Staphylococcus aureus.
AB  - Staphylococcus aureus , a leading cause of bacterial infections in humans, is
      endowed with a wealth of virulence factors that contribute to the disease
      process. Several extracellular proteolytic enzymes, including cysteine
      proteinases referred to as the staphopains (staphopain A, encoded by the scpA
      gene, and staphopain B, encoded by sspB ), have proposed roles for staphylococcal
      virulence. Here we present data regarding the distribution, copy number and
      genetic variability of the genes encoding the staphopains in a large number of S.
      aureus strains. The polymorphism of the scpA and sspB genes in three laboratory
      strains and 126 clinical isolates was analyzed by polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP). Both genes were detected in all
      isolates by PCR amplification and, based on the PCR-RFLP patterns, classified as
      four types for scpA and six types for sspB . Those with the most divergent
      patterns were subjected to DNA sequencing and compared with genomic sequence data
      for the seven available strains of S. aureus . Southern blot analysis of the scpA
      and sspB sequences indicates that they are strongly conserved as single-copy
      genes in the genome of each S. aureus strain investigated. Taken together, these
      data suggest that the staphopains have important housekeeping and/or virulence
      functions, and therefore may constitute an interesting target for the development
      of therapeutic inhibitors for the treatment of staphylococcal diseases.

PMID- 15576327
TI  - Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin
      following trauma and in dermal diseases.
AB  - During dermal injury and inflammation the serine proteases kallikreins cleave
      endogenous, multifunctional substrates (kininogens) to form bradykinin and
      kallidin. The actions of kinins are mediated by preferential binding to
      constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A
      feature of the kinin-B1 receptors is that they show low levels of expression, but
      are distinctly upregulated following tissue injury and inflammation. Because
      recent evidence suggested that kinin-B1 receptors may perform a protective role
      during inflammation, we investigated the specific occurrence of the kallikrein
      kinin components in skin biopsies obtained from normal skin, patients undergoing
      surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was
      immunolabeled in order to determine the localisation of tissue pro-kallikrein,
      kallikrein, kininogen and kinin receptors. The kinin components were visualised
      in normal, diseased and traumatised skin, except that no labelling was observed
      for kininogen in normal skin. Of the five types of tissue examined, upregulation
      of kinin-B1 receptors was observed only in skin biopsies obtained following
      surgery. In essence, the expression of kinin-B1 receptors did not appear to be
      enhanced in the other biopsies. Within the multiple steps of the inflammatory
      cascade in wound healing, our results suggest an important regulatory role for
      kinin-B1 receptors during the first phase of inflammation following injury.

PMID- 15576328
TI  - Reduction of myocardial infarction by calpain inhibitors A-705239 and A-705253 in
      isolated perfused rabbit hearts.
AB  - Two novel calpain inhibitors (A-705239 and A-705253) were studied in isolated
      perfused rabbit hearts subjected to 60-min occlusion of the ramus
      interventricularis of the left coronary artery (below the origin of the first
      diagonal branch), followed by 120 min of reperfusion. The inhibitors were added
      to the perfusion fluid in various final concentrations from the beginning of the
      experiments before the coronary artery was blocked. Hemodynamic monitoring and
      biochemical analysis of perfusion fluid from the coronary outflow were carried
      out. Myocardial infarct size and the area at risk (transiently non-perfused
      myocardium) were determined from left ventricular slices after a special staining
      procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted
      area (dead myocardium) was 77.9+/-2.3% of the area at risk in untreated controls
      ( n =12). The infarct size was significantly reduced in the presence of both
      calpain inhibitors. The best effect was achieved with 10 -8 M A-705253 ( n =8),
      which reduced ( p <0.001) the infarcted area to 49.3+/-3.9% of the area at risk,
      corresponding to an infarct reduction of 61.8%. No statistical difference was
      observed between the experimental groups in coronary perfusion, left ventricular
      pressure, and in the release of lactate dehydrogenase and creatine kinase from
      heart muscle.

PMID- 15576329
TI  - A proteinase inhibitor from Caesalpinia echinata (pau-brasil) seeds for plasma
      kallikrein, plasmin and factor XIIa.
AB  - Caesalpinia echinata is a tree belonging to the Leguminosae family. The red color
      of the trunk, looking like burning wood ('brasa' in Portuguese), is the origin of
      the name Brazil. Seeds of leguminous plants contain high amounts of serine
      proteinase inhibitors that can affect different biological processes. Here we
      show that a protein isolated from seeds of C. echinata is able to inhibit enzymes
      that participate in blood coagulation and fibrinolysis. This inhibitor (CeKI) was
      purified to homogeneity by ion exchange and reversed-phase chromatography. SDS
      PAGE indicated a single polypeptide chain with a molecular mass of 20 kDa. CeKI
      inhibits human plasma kallikrein ( K i =3.1 nM), plasmin ( K i =0.18 nM), factor
      XIIa ( K i =0.18 nM), trypsin ( K i =21.5 nM) and factor Xa ( K i =0.49 mM). CeKI
      inhibited kinin release from highmolecular- mass kininogen by kallikrein in vitro
      . The N-terminal sequence, determined by automatic Edman degradation, identified
      the inhibitor as a member of the Kunitz family. The secondary structure,
      determined by circular dichroism, is mainly a random coil followed by beta-sheet
      structure. The action of CeKI on enzymes of the blood-clotting intrinsic pathway
      was confirmed by prolongation of the activated partial thromboplastin time.

PMID- 15576330
TI  - Plasma prekallikrein/kallikrein processing by lysosomal cysteine proteases.
AB  - Plasma kallikrein plays a role in coagulation, fibrinolysis and inflammation.
      Cathepsins B and L participate in (patho)physiological processes such as peptide
      antigen processing, tissue remodeling events, protein turnover in cells, hormone
      processing and tumor invasion. The present work analyzes the processing of
      prekallikrein/kallikrein by lysosomal cathepsins. Prekallikrein is not hydrolyzed
      by catB, and catL generates an inactive fragment of prekallikrein. Both
      kallikrein chains are hydrolyzed by catL and the light chain is mainly hydrolyzed
      by catB; kallikrein activity is lower after incubation with catL compared to
      catB. Our data suggest that the plasma kallikrein/ kinin system can be controlled
      by cathepsins.

PMID- 15576331
TI  - Characteristics of the caspase-like catalytic domain of human paracaspase.
AB  - Human paracaspase has been predicted to be a member of the protein structural
      fold that encompasses protease clan CD. To determine whether paracaspase has
      catalytic activity we have expressed the region corresponding to the catalytic
      domain and used protease activity-based chemical probes to profile the putative
      active site. A leucine-based acyloxymethyl ketone probe that covalently labels
      cysteine proteases discloses a hydrophobic P 1 preference in the putative active
      site. The probe covalently labels Cys539, which is not the predicted catalytic
      site based on structural and sequence comparisons with other clan CD proteases.
      Using a combinatorial peptide substrate library approach we have been unable to
      detect amidolytic activity of paracaspase, implying that if it is a protease it
      must be very specific. We suggest a switch in the use of catalytic residues to
      generate an enzyme overlapping the canonical clan CD protease active site.

PMID- 15576332
TI  - mRNA expression analysis of a variety of apoptosis-related genes, including the
      novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment
      with carboplatin and doxorubicin.
AB  - Apoptosis is a type of programmed cell death involved in many crucial biological
      processes. It represents the basic mechanism for the action of chemotherapeutic
      agents, such as doxorubicin and carboplatin. Both are able to cause cell death
      through the induction of apoptosis in the human leukemic cell line HL-60. We
      investigated the possible alterations in the expression of apoptosis-related
      genes, including the novel BCL2L12 gene, which was recently cloned in our group.
      The kinetics of apoptosis induction and cell toxicity was investigated by DNA
      laddering and by the MTT method, respectively. Total RNA was extracted and cDNA
      was prepared by reverse transcription. BCL2 , BAX , FAS , caspase-9, caspase-3
      and BCL2L12 were amplified by PCR. Overexpression of FAS , BCL2L12 and caspase-3
      was observed after treatment of HL-60 cells for 3 or 6 h with carboplatin, while
      their expression was decreased after a 12-h treatment, demonstrating that these
      genes may take part in the early stages of apoptosis. Overexpression of the same
      genes was also observed after 6 h of treatment with doxorubicin (concomitantly
      with DNA laddering). In the case of carboplatin-induced apoptosis we detected
      down-regulation of BAX , BCL2 and caspase-9, whereas in the case of doxorubicin,
      BAX and BCL2 remained at control levels and caspase-9 was increased.

PMID- 15576333
TI  - Thermoplasma acidophilum TAA43 is an archaeal member of the eukaryotic meiotic
      branch of AAA ATPases.
AB  - Sequencing of the Thermoplasma acidophilum genome revealed a new gene, taa43 ,
      which codes for a 43-kDa protein containing one AAA domain; we therefore termed
      it Thermoplasma AAA ATPase of 43 kDa (TAA43). Close homologs of TAA43 are found
      only in related Thermoplasmales, e.g. T. volcanium and Ferroplasma acidarmanus ,
      but not in other Archaea. A detailed phylogenetic analysis showed that TAA43 and
      its homologs belong to the 'meiotic' branch of the AAA family. Although AAA
      proteins usually assemble into high-molecular-weight complexes, native TAA43 is
      predominantly dimeric except for a minor fraction eluting in the void volume of a
      sizing column. Wild-type and mutant TAA43 proteins were overexpressed in
      Escherichia coli , purified as dimers and characterized functionally. Since the
      canonical proteasome activating nucleotidase is not present in Thermoplasmales,
      TAA43 was tested for stimulation of proteasome activity, which was, however, not
      detected. Interestingly, immunoprecipitation analysis with TAA43 specific
      antibodies found a fraction of native TAA43 associated with Thermoplasma
      ribosomal proteins.

PMID- 15576334
TI  - Lipopolysaccharide binding of an exchangeable apolipoprotein, apolipophorin III,
      from Galleria mellonella.
AB  - A new role of apolipophorin III (apoLp-III) as an immune activator has emerged
      recently. To gain insight into this novel function, the interaction of apoLp-III
      with lipopoly-saccharide (LPS) was investigated. ApoLp-III from Galleria
      mellonella was incubated with LPS from Escherichia coli O55:B5, and analyzed by
      non-denaturing polyacrylamide gel electrophoresis (PAGE). Protein staining showed
      that apoLp-III mobility was significantly reduced. In addition, silver and LPS
      fluorescent staining demonstrated that LPS mobility was increased upon incubation
      with apoLp-III. This result suggests association of apoLp-III with LPS. Sodium
      dodecyl sulfate (SDS) PAGE analysis showed decreased apoLp-III mobility upon LPS
      addition, indicative of LPS apoLp-III interaction in the presence of SDS. The
      unique tyrosine residue that resides in apoLp-III was used to provide additional
      evidence for LPS binding interaction. In the absence of LPS, apoLp-III tyrosine
      fluorescence was relatively low. However, LPS addition resulted in a progressive
      increase in the fluorescence intensity, indicating tertiary rearrangement in the
      environment of tyrosine 142 upon LPS interaction. Other well-characterized apoLp
      IIIs were also examined for LPS binding. Manduca sexta , Bombyx mori and Locusta
      migratoria apoLp-III were all able to interact with LPS. The ability of apoLp-III
      to form complexes with LPS supports the proposed role of apoLp-III in innate
      immunity.

PMID- 15576335
TI  - The physiology and neurochemistry of self-injurious behavior: a nonhuman primate
      model.
AB  - Self-injurious behavior (SIB) is a serious behavioral condition that afflicts
      millions of individuals in the United States alone. The underlying factors
      contributing to the development of self-injury in people are poorly understood,
      and existing treatment strategies for this condition are limited. A low but
      persistent percentage of socially reared individually housed rhesus monkeys also
      spontaneously develop SIB. Data obtained from colony records suggest that the
      risk of developing SIB in socially reared rhesus monkeys is heightened by adverse
      early experience and subsequent stress exposure. The present review summarizes
      the physiological and neurochemical findings obtained in this nonhuman primate
      model of SIB, focusing on monoamine neurotransmitters, neuropeptides, and
      neuroendocrine systems. The results indicate that monkeys with SIB exhibit long
      lasting disturbances in central and peripheral opioid and stress response
      systems, which lead to increased levels of anxiety. Based on these findings, we
      propose an integrated developmental-neurochemical hypothesis in which SIB arises
      from adverse life events in a subset of vulnerable monkeys, is maintained by a
      persisting dysregulation of several neurochemical and physiological systems, and
      functions to periodically reduce anxiety when the levels of anxiety become
      excessive. Implications of this hypothesis for understanding self-injury in
      patients with borderline personality disorder and members of the general
      population are discussed.

PMID- 15576336
TI  - Macrophage migration inhibitory factor in rheumatoid arthritis.
AB  - Rheumatoid arthritis is characterised by the interaction of multiple mediators,
      among the most important of which are cytokines. In recent years, extensive data
      demonstrates a pivotal role for one cytokine, macrophage migration inhibitory
      factor (MIF), in fundamental events in innate and adaptive immunity. MIF has now
      been demonstrated to be involved in the pathogenesis of many diseases, but in the
      case of RA the evidence for a role of MIF is very strong. MIF is abundantly
      expressed in the serum of RA patients, and in RA synovial tissue where it
      correlates with disease activity. MIF induces synoviocyte expression of key
      proinflammatory genes including TNF, IL-1, IL-6, IL-8, cPLA2, COX2 and MMPs. MIF
      also regulates the function of endothelial cells and B cells. Moreover, MIF is
      implicated in the control of synoviocyte proliferation and apoptosis via direct
      effects on the expression of the tumor suppressor protein p53. In multiple rat
      and mouse models of RA, anti-MIF antibodies or genetic MIF deficiency are
      associated with significant inhibition of disease. MIF -/- mice further
      demonstrate increases in synovial apoptosis. That the human Mif gene is encoded
      by different functional alleles in subjects with inflammatory disease also
      provides evidence for the role of MIF in RA. The mechanism of action of MIF is
      becoming better understood. MIF appears to interact with cell surface CD74, with
      consequent activation of MAP kinases but possibly not NFkappaB intracellular
      signal transduction. This apparent selectivity may be implicated in the ability
      of MIF to antagonise the effects of glucocorticoids. As MIF expression is induced
      by glucocorticoids, inhibition of its antagonistic effects may permit enhanced
      therapeutic effect of glucocorticoids, or "steroid sparing". To date there are no
      clinical trials of MIF antagonism in any disease, but exploitation of antibody,
      soluble receptor, or small molecule approaches enabled by the unique crystal
      structure of MIF, may soon lead to the ability to test in the clinic the
      importance of this cytokine in human RA.

PMID- 15576337
TI  - Psychosocial and academic characteristics of extremely low birth weight (< or
      =800 g) adolescents who are free of major impairment compared with term-born
      control subjects.
AB  - OBJECTIVE: To compare academic and cognitive ability, attention, attitudes, and
      behavior of extremely low birth weight (ELBW) adolescents who are free of major
      impairments at 17 years of age with term-born control subjects. METHODS: Between
      January 31, 1981, and February 9, 1986, 250 infants of < or =800 g were admitted
      for intensive care in British Columbia, 98 (39%) of whom survived to late
      adolescence. Teens with major sensorimotor handicaps and/or IQ <70 were excluded
      (n = 19). Of the 79 eligible ELBW teens, 53 (67%) were assessed at 17.3 (16.3
      19.7) years (birth weight: 720 [520-800 g]; gestation: 26 [23-29] weeks). The
      test battery screened the following areas: cognitive (Wechsler Intelligence Scale
      for Adults Third Edition, 3 subtests), academic (Wide Range Achievement Test-3),
      attention (Connors' Continuous Performance Task), self-report (Harter Self
      Perception Profile for Adolescents; Job Search Attitude Inventory), and parent
      report (Child Behavior Check List). A comparison group of term born control
      subjects (n = 31) were also assessed (birth weight: 3506 [3068-4196] g;
      gestation: 40 [39-42] weeks) at age 17.8 (16.5-19.0) years. Multivariate analysis
      of variance (group x gender) was conducted for each domain (cognitive, academic,
      self-report, and parent report). RESULTS: The ELBW group showed lower cognitive
      scores (vocabulary, block design, and digit symbol) and academic skills (reading
      and arithmetic) compared with control subjects, with no gender differences. There
      were no differences in attention between the 2 groups using a repetitive computer
      task. ELBW teens reported lower scholastic, athletic, job competence, and
      romantic confidence and viewed themselves as more likely to need help from others
      in finding a job. In the behavioral domain, parents reported their ELBW teens to
      display more internalizing, more externalizing, and more total problems than the
      control teens, with ELBW boys showing more problems. ELBW teens showed a higher
      percentage of clinically significant behavior problems than control subjects.
      CONCLUSIONS: In a provincial cohort of unimpaired survivors of birth weight < or
      =800 g, psychosocial and educational vulnerabilities persist into late
      adolescence and may complicate the transition to adult life compared with their
      peers.

PMID- 15576339
TI  - Gated myocardial perfusion SPECT: basic principles, technical aspects, and
      clinical applications.
AB  - Electrocardiographically gated myocardial perfusion SPECT (GSPECT) is a state-of
      the-art technique for the combined evaluation of myocardial perfusion and left
      ventricular function within a single study. It is currently one of the most
      commonly performed cardiology procedures in a nuclear medicine department.
      Automation of the image processing and quantification has made this technique
      highly reproducible, practical, and user friendly in the clinical setting. In
      patients with coronary artery disease, gating enhances the diagnostic and
      prognostic capability of myocardial perfusion imaging, provides incremental
      information over the perfusion data, and has shown potentials for myocardial
      viability assessment and sequential follow-up after therapy. After reading this
      article, the readers will understand (a) the general principles of GSPECT and
      quantitation, (b) the methods of the image acquisition and analysis, (c)
      validation of GSPECT with other cardiac imaging modalities, and (d) application
      of the GSPECT-derived functional parameters in the clinical practice.

PMID- 15576338
TI  - A universal strategy for proteomic studies of SUMO and other ubiquitin-like
      modifiers.
AB  - Post-translational modification by the conjugation of small ubiquitin-like
      modifiers is an essential mechanism to affect protein function. Currently, only a
      limited number of substrates are known for most of these modifiers, thus limiting
      our knowledge of their role and relevance for cellular physiology. Here, we
      report the development of a universal strategy for proteomic studies of ubiquitin
      like modifiers. This strategy involves the development of stable transfected cell
      lines expressing a double-tagged modifier under the control of a tightly
      negatively regulated promoter, the induction of the expression and conjugation of
      the tagged modifier to cellular proteins, the tandem affinity purification of the
      pool of proteins covalently modified by the tagged modifier, and the
      identification of the modified proteins by LC and MS. By applying this
      methodology to the proteomic analysis of SUMO-1 and SUMO-3, we determined that
      SUMO-1 and SUMO-3 are stable proteins exhibiting half-lives of over 20 h,
      demonstrated that sumoylation with both SUMO-1 and SUMO-3 is greatly stimulated
      by MG-132 and heat shock treatment, demonstrated the preferential usage of either
      SUMO-1 or SUMO-3 for some known SUMO substrates, and identified 122 putative SUMO
      substrates of which only 27 appeared to be modified by both SUMO-1 and SUMO-3.
      This limited overlapping in the subset of proteins modified by SUMO-1 and SUMO-3
      supports that the SUMO paralogues are likely to be functionally distinct. Three
      of the novel putative SUMO substrates identified, namely the polypyrimidine tract
      binding protein-associated splicing factor PSF, the structural microtubular
      component alpha-tubulin, and the GTP-binding nuclear protein Ran, were confirmed
      as authentic SUMO substrates. The application of this universal strategy to the
      identification of the pool of cellular substrates modified by other ubiquitin
      like modifiers will dramatically increase our knowledge of the biological role of
      the different ubiquitin-like conjugations systems in the cell.

PMID- 15576340
TI  - Coincidence imaging using 2 dual-head gamma-camera systems, with and without
      attenuation correction.
AB  - OBJECTIVE: Coincidence imaging enhances the potential for imaging a greater
      number of patients with 18F-FDG in centers that do not have dedicated PET
      systems. The purpose of this study was to compare, in a clinical setting,
      coincidence imaging for tumor detection using 2 dual-head gamma-camera systems,
      one equipped with a 5/8-in. (16 mm) detector (CoDe5) and the other equipped with
      a newly designed 1-in. (25.4 mm) detector (CoDe8) with an x-ray tube installed in
      its gantry. METHODS: Thirty consecutive patients were studied by both systems
      during the same visit and had 4 image sets for comparison: CoDe5 without
      attenuation correction (CoDe5NC), CoDe8 with (CoDe8AC) and without (CoDe8NC)
      attenuation correction, and fused coincidence-CT images. The target-to-background
      ratio (T/Bg ratio) and target-to-nontarget ratio (T/NT ratio) were calculated for
      each tumor site. RESULTS: On visual assessment, 61 tumor sites were detected on
      CoDe8AC images. Of these, 59 (97%) were detected on CoDe8NC and 54 (88%) were
      detected on CoDe5NC images. Fused images improved image interpretation in 10
      patients (33%) compared with coincidence images alone. Data added by fusion were
      of clinical relevance in 6 patients (20%). On quantitative assessment, the number
      of accepted events by the CoDe8 was significantly higher than that by CoDe5 (5.21
      +/- 1.46 million vs. 1.27 +/- 0.36 million, P <0.001). When comparing CoDe5 with
      CoDe8 images without attenuation correction, the T/Bg and T/NT ratios were
      significantly higher on the CoDe8 images (P <0.0005 and P <0.0005, respectively).
      When comparing CoDe8 images with and without attenuation correction, the T/Bg
      ratio was better on the attenuation-corrected images (P <0.0005). CONCLUSION:
      Coincidence imaging with 1-in. detectors and attenuation correction improve image
      quality and, to a lesser extent, the tumor detection rate compared with the 5/8
      in. detectors and noncorrected images. The data added by fusion of coincidence
      images to CT findings were clinically relevant in 20% of the patients.

PMID- 15576341
TI  - Reducing exposure from 57Co sources during breast lymphoscintigraphy by
      optimizing energy windows and other suggested enhancements of acquisition and the
      display of images.
AB  - We set out to measure the reduction in exposure attained by using a weak 57Co
      sheet source with optimal energy windows. METHODS: Two groups of 10
      lymphoscintigraphy studies were analyzed. Group 1 consisted of 10 studies
      obtained with a stronger source of 57Co, 59 MBq (1.6 mCi) at the time of data
      acquisition, with transmission images acquired at 3 energy windows of 115-129,
      130-134, and 135-150 keV. Group 2 consisted of 10 studies with a weaker sheet
      source of 57Co, 11 MBq (0.3 mCi). Transmission images were acquired at 3 energy
      windows of 112-132, 130-134, and 135-150 keV. Same-sized regions of interest
      (ROIs) were drawn on the patient's torso (PT) and on the nonattenuated image of
      the transmission source itself (TS), all 1-min images. The counts in each ROI
      obtained over 1 min and the ratios between the TS ROI and the PT ROI were
      calculated for all of the energies. Dosimetry calculations based on measured
      exposure rates and the activity of the sheet sources were used to calculate the
      patient equivalent dose at 30 cm. RESULTS: For the 57Co energy window, group 1
      had an average ROI count of 1,955 in the TS region and 135 counts in the PT
      region. The average ratio of TS/PT was 15.4. Similarly, group 2 had an average
      ROI count of 646.4 in the TS region and 91.2 counts in the PT region. The average
      ratio of TS/PT was 8.6. The relative "outlining performance," when comparing the
      57Co and 99mTc windows, showed an average improvement when using the 57Co window
      of 4.4 and 5.8 times for group 1 and group 2, respectively (TS/PT at 57Co
      window)/(TS/PT at 99mTc window). Estimates of the patient equivalent dose per
      study were 2.30 microSv for the stronger 57Co flood source and 0.46 microSv for
      the weaker 57Co flood source, a 5-fold reduction in equivalent dose.
      Technologists received less than half of the above doses. CONCLUSION: Use of
      expanded, separate energy windows optimized for the primary 122-keV photon of
      57Co greatly improves transmission scan image quality compared with the standard
      140-keV 99mTc windows used for the delineation of the sentinel node. This
      markedly reduces exposure for all, by allowing the use of a weaker source, and
      can save time.

PMID- 15576342
TI  - Extensive skeletal muscle uptake of 18F-FDG: relation to immunosuppressants?
AB  - A case of gross skeletal muscle uptake of 18F-FDG during PET is described. The
      clinical context of immunosuppression after heart and lung transplantation and
      the absence of any other known association make the former a likely etiologic
      factor.

PMID- 15576343
TI  - Research applications of selected 123I-labeled neuroreceptor SPECT imaging
      ligands.
AB  - Neuroreceptor imaging is a promising area of brain imaging used to investigate
      various neurodegenerative and neuropsychiatric disorders. In the research
      setting, radiopharmaceuticals targeted to specific areas of the brain are used
      along with SPECT to assess and analyze functional mechanisms within brain
      structures. Utilization of the data that are collected from these studies may aid
      in the development of drug therapies that can be used to relieve symptoms or
      delay progression of certain disease states. After reading this article, the
      nuclear medicine technologist should be able to identify and describe the role of
      structures in the brain, identify various radiopharmaceuticals used and the
      disease states they demonstrate, and become familiar with the drugs used in
      treatment of these disorders.

PMID- 15576344
TI  - Nuclear medicine facility survey: SNM 2003 survey reporting on 2002 cost and
      utilization.

PMID- 15576345
TI  - Nuclear medicine technologist job satisfaction.

PMID- 15576346
TI  - Complete set of orthogonal 21st aminoacyl-tRNA synthetase-amber, ochre and opal
      suppressor tRNA pairs: concomitant suppression of three different termination
      codons in an mRNA in mammalian cells.
AB  - We describe the generation of a complete set of orthogonal 21st synthetase-amber,
      ochre and opal suppressor tRNA pairs including the first report of a 21st
      synthetase-ochre suppressor tRNA pair. We show that amber, ochre and opal
      suppressor tRNAs, derived from Escherichia coli glutamine tRNA, suppress UAG, UAA
      and UGA termination codons, respectively, in a reporter mRNA in mammalian cells.
      Activity of each suppressor tRNA is dependent upon the expression of E.coli
      glutaminyl-tRNA synthetase, indicating that none of the suppressor tRNAs are
      aminoacylated by any of the twenty aminoacyl-tRNA synthetases in the mammalian
      cytoplasm. Amber, ochre and opal suppressor tRNAs with a wide range of activities
      in suppression (increases of up to 36, 156 and 200-fold, respectively) have been
      generated by introducing further mutations into the suppressor tRNA genes. The
      most active suppressor tRNAs have been used in combination to concomitantly
      suppress two or three termination codons in an mRNA. We discuss the potential use
      of these 21st synthetase-suppressor tRNA pairs for the site-specific
      incorporation of two or, possibly, even three different unnatural amino acids
      into proteins and for the regulated suppression of amber, ochre and opal
      termination codons in mammalian cells.

PMID- 15576347
TI  - Computational method for discovery of estrogen responsive genes.
AB  - Estrogen has a profound impact on human physiology and affects numerous genes.
      The classical estrogen reaction is mediated by its receptors (ERs), which bind to
      the estrogen response elements (EREs) in target gene's promoter region. Due to
      tedious and expensive experiments, a limited number of human genes are
      functionally well characterized. It is still unclear how many and which human
      genes respond to estrogen treatment. We propose a simple, economic, yet effective
      computational method to predict a subclass of estrogen responsive genes. Our
      method relies on the similarity of ERE frames across different promoters in the
      human genome. Matching ERE frames of a test set of 60 known estrogen responsive
      genes to the collection of over 18,000 human promoters, we obtained 604 candidate
      genes. Evaluating our result by comparison with the published microarray data and
      literature, we found that more than half (53.6%, 324/604) of predicted candidate
      genes are responsive to estrogen. We believe this method can significantly reduce
      the number of testing potential estrogen target genes and provide functional
      clues for annotating part of genes that lack functional information.

PMID- 15576348
TI  - NFI and Oct-1 bend the Ad5 origin in the same direction leading to optimal DNA
      replication.
AB  - Two cellular transcription factors, nuclear factor I (NFI) and octamer binding
      protein (Oct-1), bind simultaneously to their recognition sequences in the Ad5
      origin of replication thereby enhancing initiation. Using scanning force
      microscopy we have previously shown that NFI induces a 60 degrees bend in the
      origin DNA. Here we demonstrate that Oct-1 induces a 42 degrees bend in the
      origin DNA. Simultaneous binding of NFI and Oct-1 induces an 82 degrees
      collective bend suggesting that both bends are oriented towards each other. In
      functional replication assays we further demonstrate that this extensive DNA
      bending leads to a synergistic enhancement of DNA replication. We propose that
      collective DNA bending induced by NFI and Oct-1 facilitates the optimal assembly
      of the preinitiation complex and plays an important role in the stimulatory
      mechanism of NFI and Oct-1 in replication.

PMID- 15576349
TI  - EFICAz: a comprehensive approach for accurate genome-scale enzyme function
      inference.
AB  - EFICAz (Enzyme Function Inference by Combined Approach) is an automatic engine
      for large-scale enzyme function inference that combines predictions from four
      different methods developed and optimized to achieve high prediction accuracy:
      (i) recognition of functionally discriminating residues (FDRs) in enzyme families
      obtained by a Conservation-controlled HMM Iterative procedure for Enzyme Family
      classification (CHIEFc), (ii) pairwise sequence comparison using a family
      specific Sequence Identity Threshold, (iii) recognition of FDRs in Multiple Pfam
      enzyme families, and (iv) recognition of multiple Prosite patterns of high
      specificity. For FDR (i.e. conserved positions in an enzyme family that
      discriminate between true and false members of the family) identification, we
      have developed an Evolutionary Footprinting method that uses evolutionary
      information from homofunctional and heterofunctional multiple sequence alignments
      associated with an enzyme family. The FDRs show a significant correlation with
      annotated active site residues. In a jackknife test, EFICAz shows high accuracy
      (92%) and sensitivity (82%) for predicting four EC digits in testing sequences
      that are <40% identical to any member of the corresponding training set. Applied
      to Escherichia coli genome, EFICAz assigns more detailed enzymatic function than
      KEGG, and generates numerous novel predictions.

PMID- 15576350
TI  - The role of phosphate groups in the VS ribozyme-substrate interaction.
AB  - The VS ribozyme trans-cleavage substrate interacts with the catalytic RNA via
      tertiary interactions. To study the role of phosphate groups in the ribozyme
      substrate interaction, 18 modified substrates were synthesized, where an epimeric
      phosphorothioate replaces one of the phosphate diester linkages. Sites in the
      stem-loop substrate where phosphorothioate substitution impaired reaction cluster
      in two regions. The first site is the scissile phosphate diester linkage and
      nucleotides downstream of this and the second site is within the loop region. The
      addition of manganese ions caused recovery of the rate of reaction for
      phosphorothioate substitutions between A621 and A622 and U631 and C632,
      suggesting that these two phosphate groups may serve as ligands for two metal
      ions. In contrast, significant manganese rescue was not observed for the scissile
      phosphate diester linkage implying that electrophilic catalysis by metal ions is
      unlikely to contribute to VS ribozyme catalysis. In addition, an increase in the
      reaction rate of the unmodified VS ribozyme was observed when a mixture of
      magnesium and manganese ions acted as the cofactor. One possible explanation for
      this effect is that the cleavage reaction of the VS ribozyme is rate limited by a
      metal dependent docking of the substrate on the ribozyme.

PMID- 15576351
TI  - DmGEN, a novel RAD2 family endo-exonuclease from Drosophila melanogaster.
AB  - A novel endo-exonuclease, DmGEN (Drosophila Melanogaster XPG-like endonuclease),
      was identified in D.melanogaster. DmGEN is composed of five exons and four
      introns, and the open reading frame encodes a predicted product of 726 amino acid
      residues with a molecular weight of 82.5 kDa and a pI of 5.36. The gene locus on
      Drosophila polytene chromosomes was detected at 64C9 on the left arm of
      chromosome 3 as a single site. The encoded protein showed a relatively high
      degree of sequence homology with the RAD2 nucleases, especially XPG. Although the
      XPG-N- and XPG-I-domains are highly conserved in sequence, locations of the
      domains are similar to those of FEN-1 and EXO-1, and the molecular weight of the
      protein is close to that of EXO-1. In vitro, DmGEN showed endonuclease and 3'-5'
      exonuclease activities with both single-stranded DNA (ssDNA) and double-stranded
      DNA (dsDNA), but the endonuclease action with dsDNA was quite specific: 5'-3'
      exonuclease activity was found to occur with nicked DNA, while dsDNA was
      endonucleolytically cut at 3-4 bp from the 5' end. Homologs are widely found in
      mammals and higher plants. The data suggest that DmGEN belongs to a new class of
      RAD2 nuclease.

PMID- 15576352
TI  - Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB
      proteins.
AB  - The Escherichia coli AlkB protein repairs 1-methyladenine (1-meA) and 3
      methylcytosine (3-meC) lesions in DNA and RNA by oxidative demethylation, a
      reaction requiring ferrous iron and 2-oxoglutarate as cofactor and co-substrate,
      respectively. Here, we have studied the activity of AlkB proteins on 3
      methylthymine (3-meT) and 1-methylguanine (1-meG), two minor lesions which are
      structurally analogous to 1-meA and 3-meC. AlkB as well as the human AlkB
      homologues, hABH2 and hABH3, were all able to demethylate 3-meT in a DNA
      oligonucleotide containing a single 3-meT residue. Also, 1-meG lesions introduced
      by chemical methylation of tRNA were efficiently removed by AlkB. Unlike 1-meA
      and 3-meC, nucleosides or bases corresponding to 1-meG or 3-meT did not stimulate
      the uncoupled, AlkB-mediated decarboxylation of 2-oxoglutarate. Our data show
      that 3-meT and 1-meG are repaired by AlkB, but indicate that the recognition of
      these substrates is different from that in the case of 1-meA and 3-meC.

PMID- 15576353
TI  - DNA polymerase delta, RFC and PCNA are required for repair synthesis of large
      looped heteroduplexes in Saccharomyces cerevisiae.
AB  - Small looped mispairs are corrected by DNA mismatch repair (MMR). In addition, a
      distinct process called large loop repair (LLR) corrects loops up to several
      hundred nucleotides in extracts of bacteria, yeast or human cells. Although LLR
      activity can be readily demonstrated, there has been little progress in
      identifying its protein components. This study identified some of the yeast
      proteins responsible for DNA repair synthesis during LLR. Polyclonal antisera to
      either Pol31 or Pol32 subunits of polymerase delta efficiently inhibited LLR in
      extracts by blocking repair just prior to gap filling. Gap filling was inhibited
      regardless of whether the loop was retained or removed. These experiments suggest
      polymerase delta is uniquely required in yeast extracts for LLR-associated
      synthesis. Similar results were obtained with antisera to the clamp loader
      proteins Rfc3 and Rfc4, and to PCNA, i.e. LLR was inhibited just prior to gap
      filling for both loop removal and loop retention. Thus PCNA and RFC seem to act
      in LLR only during repair synthesis, in contrast to their roles at both pre- and
      post-excision steps of MMR. These biochemical experiments support the idea that
      yeast polymerase delta, RFC and PCNA are required for large loop DNA repair
      synthesis.

PMID- 15576354
TI  - Analysis of transcription asymmetries along the tRNAE-COB operon: evidence for
      transcription attenuation and rapid RNA degradation between coding sequences.
AB  - Mitochondrial gene expression in yeast is believed to be regulated predominantly
      at the post-transcriptional level. However, the contribution of mitochondrial
      transcription and RNA-turnover rates to differential gene regulation is still
      largely unknown. Mitochondrial run-on transcription and hybrid selection assays
      showed that some of the multigenic transcription units of the mitochondrial
      genome are transcribed evenly, whereas others are transcribed asymmetrically,
      with higher transcription rates for promoter-proximal genes, than for promoter
      distal genes. The tRNA(E)-cytochrome b (COB) operon was analyzed in detail to
      investigate the mechanisms underlying transcription rate asymmetries in yeast
      mitochondria. We showed that a drop in transcription rates occurs in a particular
      region between the coding sequences and is independent of the coding sequence of
      the downstream COB gene. Deletion of the region between tRNA(E) and COB coding
      sequences decreases the drop in transcription rates. Deletion of the nuclear gene
      encoding the Pet 127 protein, which is involved in mitochondrial RNA 5'
      processing and degradation, also partially relieves transcriptional asymmetry.
      Therefore, asymmetry is probably due to a combination of attenuated transcription
      at specific sites between the coding sequences and very rapid RNA degradation.

PMID- 15576355
TI  - Thermoadaptation trait revealed by the genome sequence of thermophilic
      Geobacillus kaustophilus.
AB  - We present herein the first complete genome sequence of a thermophilic Bacillus
      related species, Geobacillus kaustophilus HTA426, which is composed of a 3.54 Mb
      chromosome and a 47.9 kb plasmid, along with a comparative analysis with five
      other mesophilic bacillar genomes. Upon orthologous grouping of the six bacillar
      sequenced genomes, it was found that 1257 common orthologous groups composed of
      1308 genes (37%) are shared by all the bacilli, whereas 839 genes (24%) in the
      G.kaustophilus genome were found to be unique to that species. We were able to
      find the first prokaryotic sperm protamine P1 homolog, polyamine synthase,
      polyamine ABC transporter and RNA methylase in the 839 unique genes; these may
      contribute to thermophily by stabilizing the nucleic acids. Contrasting results
      were obtained from the principal component analysis (PCA) of the amino acid
      composition and synonymous codon usage for highlighting the thermophilic
      signature of the G.kaustophilus genome. Only in the PCA of the amino acid
      composition were the Bacillus-related species located near, but were
      distinguishable from, the borderline distinguishing thermophiles from mesophiles
      on the second principal axis. Further analysis revealed some asymmetric amino
      acid substitutions between the thermophiles and the mesophiles, which are
      possibly associated with the thermoadaptation of the organism.

PMID- 15576356
TI  - Influence of a fluorobenzene nucleobase analogue on the conformational
      flexibility of RNA studied by molecular dynamics simulations.
AB  - Chemically modified bases are frequently used to stabilize nucleic acids, to
      study the driving forces for nucleic acid structure formation and to tune DNA and
      RNA hybridization conditions. In particular, fluorobenzene and
      fluorobenzimidazole base analogues can act as universal bases able to pair with
      any natural base and to stabilize RNA duplex formation. Although these base
      analogues are compatible with an A-form RNA geometry, little is known about the
      influence on the fine structure and conformational dynamics of RNA. In the
      present study, nano-second molecular dynamics (MD) simulations have been
      performed to characterize the dynamics of RNA duplexes containing a central 1'
      deoxy-1'-(2,4-difluorophenyl)-beta-D-ribofuranose base pair or opposite to an
      adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'
      deoxy-1'-(phenyl)-beta-D-ribofuranose opposite to an adenine was also
      investigated. The MD simulations indicate a stable overall A-form geometry for
      the RNAs with base analogues. However, the presence of the base analogues caused
      a locally enhanced mobility of the central bases inducing mainly base pair shear
      and opening motions. No stable 'base-paired' geometry was found for the base
      analogue pair or the base analogue:adenine pairs, which explains in part the
      universal base character of these analogues. Instead, the conformational
      fluctuations of the base analogues lead to an enhanced accessibility of the bases
      in the major and minor grooves of the helix compared with a regular base pair.

PMID- 15576357
TI  - PreSPI: a domain combination based prediction system for protein-protein
      interaction.
AB  - With the accumulation of protein and its related data on the Internet, many
      domain-based computational techniques to predict protein interactions have been
      developed. However, most techniques still have many limitations when used in real
      fields. They usually suffer from low accuracy in prediction and do not provide
      any interaction possibility ranking method for multiple protein pairs. In this
      paper, we propose a probabilistic framework to predict the interaction
      probability of proteins and develop an interaction possibility ranking method for
      multiple protein pairs. Using the ranking method, one can discern the protein
      pairs that are more likely to interact with each other in multiple protein pairs.
      The validity of the prediction model was evaluated using an interacting set of
      protein pairs in yeast and an artificially generated non-interacting set of
      protein pairs. When 80% of the set of interacting protein pairs in the DIP
      (Database of Interacting Proteins) was used as a learning set of interacting
      protein pairs, high sensitivity (77%) and specificity (95%) were achieved for the
      test groups containing common domains with the learning set of proteins within
      our framework. The stability of the prediction model was also evident when tested
      over DIP CORE, HMS-PCI and TAP data. In the validation of the ranking method, we
      reveal that some correlations exist between the interacting probability and the
      accuracy of the prediction.

PMID- 15576358
TI  - Functional clues for hypothetical proteins based on genomic context analysis in
      prokaryotes.
AB  - Three integrated genomic context methods were used to annotate uncharacterized
      proteins in 102 bacterial genomes. Of 7853 orthologous groups with unknown
      function containing 45,110 proteins, 1738 groups could be linked to functionally
      associated partners. In many cases, those partners are uncharacterized themselves
      (hinting at newly identified modules) or have been described in general terms
      only. However, we were able to assign pathways, cellular processes or physical
      complexes for 273 groups (encompassing 3624 previously functionally
      uncharacterized proteins).

PMID- 15576359
TI  - Paradoxical homozygous expression from heterozygotes and heterozygous expression
      from homozygotes as a consequence of transcriptional infidelity through a
      polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia.
AB  - Canine cyclic neutropenia is an autosomal recessive disease in which the number
      of neutrophils, the primary blood phagocyte, oscillates between almost zero and
      normal values with two week frequency. We previously found that the causative
      mutation is an insertion of an extra adenine residue within a tract of nine A's
      in exon 21 of the 27 exon canine AP3B1 gene. In the course of identifying the
      mutation, however, we observed an unusual phenomenon: heterozygous carrier dogs,
      who have one normal allele and one mutant allele, produce a homogeneous
      population of normal AP3B1 transcripts (containing nine A's), but homozygous
      affected dogs, who have two mutant alleles, produce a heterogeneous population of
      AP3B1 mRNA containing mutant transcripts with ten A's and, unexpectedly, wild
      type transcripts with nine A's. By RT-PCR subclone analysis and use of an in
      vitro reporter assay, we show that there is a high frequency of errors made
      during the transcription of homopolymeric adenine sequences, such that the A
      tract in the mRNA is frequently shortened or lengthened by an extra residue. Out
      of frame transcripts are degraded, accounting for this paradox through the
      preferential accumulation of normal message from mutant alleles.

PMID- 15576360
TI  - Chemotherapeutic deletion of CTG repeats in lymphoblast cells from DM1 patients.
AB  - Myotonic dystrophy type 1 (DM1) is caused by the expansion of a (CTG).(CAG)
      repeat in the DMPK gene on chromosome 19q13.3. At least 17 neurological diseases
      have similar genetic mutations, the expansion of DNA repeats. In most of these
      disorders, the disease severity is related to the length of the repeat expansion,
      and in DM1 the expanded repeat undergoes further elongation in somatic and
      germline tissues. At present, in this class of diseases, no therapeutic approach
      exists to prevent or slow the repeat expansion and thereby reduce disease
      severity or delay disease onset. We present initial results testing the
      hypothesis that repeat deletion may be mediated by various chemotherapeutic
      agents. Three lymphoblast cell lines derived from two DM1 patients treated with
      either ethylmethanesulfonate (EMS), mitomycin C, mitoxantrone or doxorubicin, at
      therapeutic concentrations, accumulated deletions following treatment. Treatment
      with EMS frequently prevented the repeat expansion observed during growth in
      culture. A significant reduction of CTG repeat length by 100-350 (CTG).(CAG)
      repeats often occurred in the cell population following treatment with these
      drugs. Potential mechanisms of drug-induced deletion are presented.

PMID- 15576361
TI  - Does the cytotoxic effect of transient amyloid oligomers from common equine
      lysozyme in vitro imply innate amyloid toxicity?
AB  - In amyloid diseases, it is not evident which protein aggregates induce cell death
      via specific molecular mechanisms and which cause damage because of their mass
      accumulation and mechanical properties. We showed that equine lysozyme assembles
      into soluble amyloid oligomers and protofilaments at pH 2.0 and 4.5, 57 degrees
      C. They bind thioflavin-T and Congo red similar to common amyloid structures, and
      their morphology was monitored by atomic force microscopy. Molecular volume
      evaluation from microscopic measurements allowed us to identify distinct types of
      oligomers, ranging from tetramer to octamer and 20-mer. Monomeric lysozyme and
      protofilaments are not cytotoxic, whereas the oligomers induce cell death in
      primary neuronal cells, primary fibroblasts, and the neuroblastoma IMR-32 cell
      line. Cytotoxicity was accessed by ethidium bromide staining, MTT reduction, and
      TUNEL assays. Primary cultures were more susceptible to the toxic effect induced
      by soluble amyloid oligomers than the neuroblastoma cell line. The cytotoxicity
      correlates with the size of oligomers; the sample incubated at pH 4.5 and
      containing larger oligomers, including 20-mer, appears to be more cytotoxic than
      the lysozyme sample kept at pH 2.0, in which only tetramers and octamers were
      found. Soluble amyloid oligomers may assemble into rings; however, there was no
      correlation between the quantity of rings in the sample and its toxicity. The
      cytotoxicity of transient oligomeric species of the ubiquitous protein lysozyme
      indicates that this is an intrinsic feature of protein amyloid aggregation, and
      therefore soluble amyloid oligomers can be used as a primary therapeutic target
      and marker of amyloid disease.

PMID- 15576362
TI  - Generation of a recombinant apolipoprotein E variant with improved biological
      functions: hydrophobic residues (LEU-261, TRP-264, PHE-265, LEU-268, VAL-269) of
      apoE can account for the apoE-induced hypertriglyceridemia.
AB  - To identify the residues in the carboxyl-terminal region 260-299 of human
      apolipoprotein E (apoE) that contribute to hypertriglyceridemia, two sets of
      conserved, hydrophobic amino acids between residues 261 and 283 were mutated to
      alanines, and recombinant adenoviruses expressing these apoE mutants were
      generated. Adenovirus-mediated gene transfer of apoE4-mut1 (apoE4 (L261A, W264A,
      F265A, L268A, V269A)) in apoE-deficient mice (apoE(-/-)) corrected plasma
      cholesterol levels and did not cause hypertriglyceridemia. In contrast, gene
      transfer of apoE4-mut2 (apoE4 (W276A, L279A, V280A, V283A)) did not correct
      hypercholesterolemia and induced mild hypertriglyceridemia. ApoE-induced
      hyperlipidemia was corrected by co-infection with a recombinant adenovirus
      expressing human lipoprotein lipase. Both apoE4 mutants caused only a small
      increase in hepatic very low density lipoprotein-triglyceride secretion. Density
      gradient ultracentrifugation analysis of plasma and electron microscopy showed
      that wild-type apoE4 and apoE4-mut2 displaced apoA-I from the high density
      lipoprotein (HDL) region and promoted the formation of discoidal HDL, whereas the
      apoE4-mut1 did not displace apoA-I from HDL and promoted the formation of
      spherical HDL. The findings indicate that residues Leu-261, Trp-264, Phe-265, Leu
      268, and Val-269 of apoE are responsible for hypertriglyceridemia and also
      interfere with the formation of HDL. Substitutions of these residues by alanine
      provide a recombinant apoE form with improved biological functions.

PMID- 15576363
TI  - Helicobacter-induced intestinal metaplasia in the stomach correlates with Elk-1
      and serum response factor induction of villin.
AB  - Chronic Helicobacter pylori infection results in serious sequelae, including
      atrophy, intestinal metaplasia, and gastric cancer. Intestinal metaplasia in the
      stomach is defined by the presence of intestine-like cells expressing enterocyte
      specific markers, such as villin. In this study, we demonstrate that villin is
      expressed in intestine-like cells that develop after chronic infection with H.
      pylori in both human stomach and in a mouse model. Transfection studies were used
      to identify specific regions of the villin promoter that are inducible by
      exposure of the cells to H. pylori. We demonstrated that induction of the villin
      promoter by H. pylori in a human gastric adenocarcinoma cell line (AGS) required
      activation of the Erk pathway. Elk-1 and the serum response factor (SRF) are
      downstream transcriptional targets of the Erk pathway. We observed inducible
      binding of Elk-1 and the SRF after 3 and 24 h of treatment with H. pylori,
      suggesting that the bacteria alone are sufficient to initiate a cascade of
      signaling events responsible for villin expression. Thus, H. pylori induction of
      villin in the stomach correlates with activation and cooperative binding of Elk-1
      and the SRF to the proximal promoter of villin.

PMID- 15576364
TI  - Calcium-dependent plasma membrane binding and cell lysis by perforin are mediated
      through its C2 domain: A critical role for aspartate residues 429, 435, 483, and
      485 but not 491.
AB  - The lymphocyte pore-forming protein perforin is essential for maintaining immune
      homeostasis and for effective defense against intracellular pathogens. To date,
      there have been no reported structure-function studies to substantiate the
      function of any putative domains of perforin, which have been postulated totally
      on primary sequence similarities with domains in other proteins. In this report,
      we have used recently developed modalities for expressing full-length perforin
      and robust functional assays to investigate one of the hallmarks of perforin
      function: its absolute dependence on calcium for lipid binding and cell lysis. We
      provide, for the first time, experimental evidence that the predicted C-terminal
      C2 motif constitutes a functional domain that is responsible for membrane binding
      of perforin. Whereas conserved aspartate residues at positions 429, 435, 483, and
      485 were essential for calcium-dependent plasma membrane binding and cell lysis,
      the contribution of Asp-491 was limited. Finally, after experimentally verifying
      an optimized three-dimensional model, we have made predictions on the impact of
      two inherited perforin mutations of the C2 domain on calcium-dependent lipid
      binding and cell lysis.

PMID- 15576365
TI  - Interaction of neuronal calcium sensor-1 and ADP-ribosylation factor 1 allows
      bidirectional control of phosphatidylinositol 4-kinase beta and trans-Golgi
      network-plasma membrane traffic.
AB  - We have identified a novel Ca(2+)-dependent interaction between neuronal calcium
      sensor-1 (NCS-1) and the GTPase ARF1. Both of these proteins are localized to the
      Golgi complex, and both regulate phosphatidylinositol 4-kinase IIIbeta
      (PI(4)Kbeta). Spatial and temporal control of phosphatidylinositol 4-phosphate
      levels through activation of PI(4)Kbeta is important for the recruitment of
      trafficking complexes to the trans-Golgi network (TGN) and vesicular traffic from
      this organelle. The NCS-1-ARF1 interaction and its specificity have been
      demonstrated through in vitro binding assays, in vitro enzyme assay, and through
      functional cellular assays. We show that NCS-1 can exert bidirectional effects to
      activate PI(4)Kbeta on its own or inhibit the activation by ARF1. NCS-1 was shown
      to modulate the effects of expression of ARF mutants that disrupt Golgi
      morphology and to recruit GDP-loaded ARF to the Golgi complex in a Ca(2+)
      dependent manner. We demonstrate antagonist effects of NCS-1 and ARF on
      constitutive and regulated exocytosis. The NCS-1-ARF1 interaction provides
      evidence for functional cross-talk between Ca(2+)-dependent and ARF-dependent
      pathways in TGN to plasma membrane traffic.

PMID- 15576366
TI  - Targeting a novel Plasmodium falciparum purine recycling pathway with specific
      immucillins.
AB  - Plasmodium falciparum is unable to synthesize purine bases and relies upon purine
      salvage and purine recycling to meet its purine needs. We report that purines
      formed as products of polyamine synthesis are recycled in a novel pathway in
      which 5'-methylthioinosine is generated by adenosine deaminase. The action of P.
      falciparum purine nucleoside phosphorylase is a convergent step of purine
      salvage, converting both 5'-methylthioinosine and inosine to hypoxanthine. We
      used accelerator mass spectrometry to verify that 5'-methylthioinosine is an
      active nucleic acid precursor in P. falciparum. Prior studies have shown that
      inhibitors of purine salvage enzymes kill malaria, but potent malaria-specific
      inhibitors of these enzymes have not been described previously. 5'-Methylthio
      immucillin-H, a transition state analogue inhibitor that is selective for
      malarial relative to human purine nucleoside phosphorylase, kills P. falciparum
      in culture. Immucillins are currently in clinical trials for other indications
      and may also have application as anti-malarials.

PMID- 15576367
TI  - Functional demonstration of reverse transsulfuration in the Mycobacterium
      tuberculosis complex reveals that methionine is the preferred sulfur source for
      pathogenic Mycobacteria.
AB  - Methionine can be used as the sole sulfur source by the Mycobacterium
      tuberculosis complex although it is not obvious from examination of the genome
      annotation how these bacteria utilize methionine. Given that genome annotation is
      a largely predictive process, key challenges are to validate these predictions
      and to fill in gaps for known functions for which genes have not been annotated.
      We have addressed these issues by functional analysis of methionine metabolism.
      Transport, followed by metabolism of (35)S methionine into the cysteine adduct
      mycothiol, demonstrated the conversion of exogenous methionine to cysteine.
      Mutational analysis and cloning of the Rv1079 gene showed it to encode the key
      enzyme required for this conversion, cystathionine gamma-lyase (CGL). Rv1079,
      annotated metB, was predicted to encode cystathionine gamma-synthase (CGS), but
      demonstration of a gamma-elimination reaction with cystathionine as well as the
      gamma-replacement reaction yielding cystathionine showed it encodes a
      bifunctional CGL/CGS enzyme. Consistent with this, a Rv1079 mutant could not
      incorporate sulfur from methionine into cysteine, while a cysA mutant lacking
      sulfate transport and a methionine auxotroph was hypersensitive to the CGL
      inhibitor propargylglycine. Thus, reverse transsulfuration alone, without any
      sulfur recycling reactions, allows M. tuberculosis to use methionine as the sole
      sulfur source. Intracellular cysteine was undetectable so only the CGL reaction
      occurs in intact mycobacteria. Cysteine desulfhydrase, an activity we showed to
      be separable from CGL/CGS, may have a role in removing excess cysteine and could
      explain the ability of M. tuberculosis to recycle sulfur from cysteine, but not
      methionine.

PMID- 15576368
TI  - Mapping the functional domains of the Golgi stacking factor GRASP65.
AB  - The Golgi reassembly stacking protein (GRASP) family has been implicated in the
      stacking of Golgi cisternae and the regulation of Golgi disassembly/reassembly
      during mitosis in mammalian cells. GRASP65 is a dimer that can directly link
      adjacent surfaces through trans-oligomerization in a mitotically regulated
      manner. Here we show that the N-terminal GRASP domain (amino acids 1-201) is both
      necessary and sufficient for dimerization and trans-oligomerization but is not
      mitotically regulated. The C-terminal serine/proline-rich domain (amino acids 202
      446) cannot dimerize nor can it link adjacent surfaces. It does, however, confer
      mitotic regulation on the GRASP domain through multiple sites phosphorylated by
      the mitotic kinases, cdc2/B1, and the polo-like kinase. Transient expression
      corroborated these results by showing that the GRASP domain alone inhibited
      mitotic fragmentation of the Golgi apparatus.

PMID- 15576369
TI  - Transgenic expression of dominant negative tuberin through a strong constitutive
      promoter results in a tissue-specific tuberous sclerosis phenotype in the skin
      and brain.
AB  - Tuberous sclerosis (TS) is a common autosomal dominant disorder caused by loss or
      malfunction of hamartin (tsc1) or tuberin (tsc2). Many lesions in TS do not
      demonstrate loss of heterozygosity for these genes, implying that dominant
      negative forms of these genes may account for some hamartomas and neoplasms in
      TS. To test this hypothesis, we expressed a dominant negative allele of tuberin
      (DeltaRG) behind the cytomegalovirus promoter in NIH3T3 cells and transgenic
      mice. This allele binds hamartin but has a deletion in the C terminus of tuberin,
      leading to constitutive activation of rap1 and rab5/rabaptin. Expression of
      DeltaRG in NIH3T3 cells led to a strong induction of reactive oxygen species,
      induction of vascular endothelial growth factor, and malignant transformation in
      vivo. Expression of DeltaRG driven by the constitutive cytomegalovirus promoter
      led to high level expression in all murine tissues examined, including skin,
      kidney, liver, and brain. Surprisingly, mice expressing the DeltaRG transgene
      developed a fibrovascular collagenoma in the dermis, which closely resembles the
      Shagreen patch observed in human patients with TS. In addition, numerous small
      subpial collections of external granule cells in the cerebellum were observed,
      which may be the murine equivalent of subependymal giant cell astrocytomas or
      tubers commonly seen in TS patients. Thus, expression of a dominant negative
      tuberin in multiple tissues can lead to a tissue-specific phenotype resembling
      some of the findings in human TS. Our data are the first to demonstrate that
      specific signaling abnormalities underlie specific hamartomas in a model of a
      human genetic disorder.

PMID- 15576370
TI  - Annexin A5 down-regulates surface expression of tissue factor: a novel mechanism
      of regulating the membrane receptor repertoir.
AB  - Phosphatidylserine (PtdSer) is exposed on the external leaflet of the plasma
      membrane during apoptosis. The protein annexin A5 (anxA5) shows high affinity for
      PtdSer. When anxA5 binds to the PtdSer-expressing membranes during apoptosis, it
      crystallizes as an extended two-dimensional network and activates thereby a novel
      portal of cell entry that results in the internalization of the PtdSer-expressing
      membrane patches. This novel pathway of cell entry is potentially involved in the
      regulation of the surface expression of membrane receptors. In this study we
      report the regulation of surface expression of the initiator of blood coagulation
      tissue factor (TF) by this novel pathway of cell entry. AnxA5 induces the
      internalization of tissue factor expressed on the surface of apoptotic THP-1
      macrophages. This down-regulation depends on the abilities of anxA5 to bind to
      PtdSer and to form a two-dimensional crystal at the membrane. We furthermore show
      that THP-1 cells produce and externalize anxA5 that cause the internalization of
      TF in an autocrine type of mechanism. We extended our in vitro work to the in
      vivo situation and show in a mouse model that anxA5 causes the down-regulation of
      TF expression by smooth muscle cells of the media of the carotid artery that was
      mechanically injured. In conclusion, anxA5 down-regulates surface-expressed TF by
      activating the novel portal of cell entry. This mechanism may be part of a more
      general autocrine function of anxA5 to regulate the plasma membrane receptor
      repertoir under stress conditions associated with the surface expression of
      PtdSer.

PMID- 15576371
TI  - Novel anion-independent iron coordination by members of a third class of
      bacterial periplasmic ferric ion-binding proteins.
AB  - The uptake of the element iron is vital for the survival of most organisms.
      Numerous pathogenic Gram-negative bacteria utilize a periplasm-to-cytosol ATP
      binding cassette transport pathway to transport this essential atom in to the
      cell. In this study, we investigated the Yersinia enterocolitica (YfuA) and
      Serratia marcescens (SfuA) iron-binding periplasmic proteins. We have determined
      the 1.8-angstroms structures of iron-loaded (YfuA) and iron-free (SfuA) forms of
      this class of proteins. Although the sequence of these proteins varies
      considerably from the other members of the transferrin structural superfamily,
      they adopt the same three-dimensional fold. The iron-loaded YfuA structure
      illustrates the unique nature of this new class of proteins in that they are able
      to octahedrally coordinate the ferric ion in the absence of a bound anion. The
      iron-free SfuA structure contains a bound citrate anion in the iron-binding cleft
      that tethers the N- and C-terminal domains of the apo protein and stabilizes the
      partially open structure.

PMID- 15576372
TI  - Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK)
      ubiquitination and degradation.
AB  - Serum and glucocorticoid-regulated kinase (SGK) plays a key role in the
      regulation of epithelial Na+ transport. SGK phosphorylates Nedd4-2, an E3
      ubiquitin-protein ligase that targets the epithelial Na+ channel (ENaC) for
      degradation. Phosphorylation increases Na+ transport by reducing Nedd4-2 binding
      to ENaC, which increases ENaC expression at the cell surface. Thus, SGK
      expression must be tightly controlled to maintain Na+ homeostasis. This occurs in
      part by regulation of SGK transcription; a variety of signals including steroid
      hormones (aldosterone and glucocorticoids) increase SGK levels by inducing
      transcription of SGK. However, SGK has a short half-life, suggesting that SGK
      levels might also be controlled by regulation of SGK degradation. Here we found
      that SGK degradation is mediated in part by Nedd4-2. Consistent with this model,
      overexpression of Nedd4-2 decreased steady-state levels of SGK in a dose
      dependent manner by increasing SGK ubiquitination and degradation in the 26S
      proteasome. Conversely, silencing of Nedd4-2 by RNA interference stabilized SGK.
      Nedd4-2 phosphorylation potentiates SGK degradation; degradation was reduced by
      Nedd4-2 and SGK mutations that disrupt phosphorylation or by inhibition of SGK
      kinase activity. Together with previous work, the data support a model in which
      SGK and Nedd4-2 regulate one another in a reciprocal manner. SGK phosphorylates
      Nedd4-2, which reduces Nedd4-2 binding and inhibition of ENaC. Conversely,
      phosphorylation increases Nedd4-2-mediated degradation of SGK. Thus, by
      phosphorylating Nedd4-2, SGK induces its own degradation. This feedback
      inhibition may fine-tune the regulation of epithelial Na+ absorption.

PMID- 15576373
TI  - Protease-activated receptor-1 activation of endothelial cells induces protein
      kinase Calpha-dependent phosphorylation of syntaxin 4 and Munc18c: role in
      signaling p-selectin expression.
AB  - Endothelial cells exhibit regulated exocytosis in response to inflammatory
      mediators such as thrombin and histamine. The exocytosis of Weibel-Palade bodies
      (WPBs) containing von Willebrand factor, P-selectin, and interleukin-8 within
      minutes after stimulation is important for vascular homeostasis. SNARE proteins
      are key components of the exocytic machinery in neurons and some secretory cells,
      but their role in regulating exocytosis in endothelial cells is not well
      understood. We examined the function of SNARE proteins in mediating exocytosis of
      WPBs in endothelial cells. We identified the presence of syntaxin 4, syntaxin 3,
      and the high affinity syntaxin 4-regulatory protein Munc18c in human lung
      microvascular endothelial cells. Small interfering RNA-induced knockdown of
      syntaxin 4 (but not of syntaxin 3) inhibited exocytosis of WPBs as detected by
      the reduction in thrombin-induced cell surface P-selectin expression. Thrombin
      ligation of protease-activated receptor-1 activated the phosphorylation of
      syntaxin 4 and Munc18c, which, in turn, disrupted the interaction between
      syntaxin 4 and Munc18. Protein kinase Calpha activation was required for the
      phosphorylation of syntaxin 4 and Munc18c as well as the cell surface expression
      of P-selectin. We also observed that syntaxin 4 knockdown inhibited the adhesion
      of neutrophils to thrombin-activated endothelial cells, demonstrating the
      functional role of syntaxin 4 in promoting endothelial adhesivity. Thus, protease
      activated receptor-1-induced protein kinase Calpha activation and phosphorylation
      of syntaxin 4 and Munc18c are required for the cell surface expression of P
      selectin and the consequent binding of neutrophils to endothelial cells.

PMID- 15576374
TI  - Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes
      apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in
      vivo.
AB  - Signaling through NF-kappaB has been implicated in the malignant phenotype as
      well as the chemoresistance of various cancers. Here we show that the natural
      compounds acetyl-beta-boswellic acid and acetyl-11-keto-beta-boswellic acid
      (AKbetaBA) inhibit proliferation and elicit cell death in chemoresistant androgen
      independent PC-3 prostate cancer cells in vitro and in vivo. Induction of
      apoptosis was demonstrated in cultured PC-3 cells by several parameters including
      mitochondrial cytochrome c release and DNA fragmentation. At the molecular level
      these compounds inhibit constitutively activated NF-kappaB signaling by
      intercepting the IkappaB kinase (IKK) activity; signaling through the interferon
      stimulated response element remained unaffected, suggesting specificity for IKK
      inhibition. The impaired phosphorylation of p65 and the reduced nuclear
      translocation of NF-kappaB proteins were associated with down-regulation of the
      constitutively overexpressed and NF-kappaB-dependent antiapoptotic proteins Bcl-2
      and Bcl-x(L). In addition, expression of cyclin D1, a crucial cell cycle
      regulator, was reduced as well. Down-regulation of IKK by antisense
      oligodeoxynucleotides confirmed the essential role of IKK inhibition for the
      proliferation of the PC-3 cells. Both compounds tested were active in vivo, yet
      AKbetaBA proved to be far superior. Indeed, topical application of water-soluble
      AKbetaBA-gamma-cyclodextrin on PC-3 tumors xenografted onto chick chorioallantoic
      membranes induced concentration-dependent inhibition of proliferation as well as
      apoptosis. Similarly, in nude mice carrying PC-3 tumors, systemic application of
      AKbetaBA-gamma-cyclodextrin inhibited tumor growth and triggered apoptosis in the
      absence of detectable systemic toxicity. Thus, AKbetaBA and related compounds
      acting on IKK might provide a novel approach for the treatment of chemoresistant
      human tumors such as androgen-independent human prostate cancers.

PMID- 15576375
TI  - Lipopolysaccharide transport to the bacterial outer membrane in spheroplasts.
AB  - The mechanism of lipopolysaccharide (LPS) transport in Gram-negative bacteria
      from the inner membrane to the outer membrane is largely unknown. Here, we
      investigated the possibility that LPS transport proceeds via a soluble
      intermediate associated with a periplasmic chaperone analogous to the Lol
      dependent transport mechanism of lipoproteins. Whereas newly synthesized
      lipoproteins could be released from spheroplasts of Escherichia coli upon
      addition of a periplasmic extract containing LolA, de novo synthesized LPS was
      not released. We demonstrate that LPS synthesized de novo in spheroplasts co
      fractionated with the outer membranes and that this co-fractionation was
      dependent on the presence in the spheroplasts of a functional MsbA protein, the
      protein responsible for the flip-flop of LPS across the inner membrane. The outer
      membrane localization of the LPS was confirmed by its modification by the outer
      membrane enzyme CrcA (PagP). We conclude that a substantial amount of LPS was
      translocated to the outer membrane in spheroplasts, suggesting that transport
      proceeds via contact sites between the two membranes. In contrast to LPS, de novo
      synthesized phospholipids were not transported to the outer membrane in
      spheroplasts. Apparently, LPS and phospholipids have different requirements for
      their transport to the outer membrane.

PMID- 15576376
TI  - Group VIA phospholipase A2 forms a signaling complex with the calcium/calmodulin
      dependent protein kinase IIbeta expressed in pancreatic islet beta-cells.
AB  - Insulin-secreting pancreatic islet beta-cells express a Group VIA Ca(2+)
      independent phospholipase A(2) (iPLA(2)beta) that contains a calmodulin binding
      site and protein interaction domains. We identified Ca(2+)/calmodulin-dependent
      protein kinase IIbeta (CaMKIIbeta) as a potential iPLA(2)beta-interacting protein
      by yeast two-hybrid screening of a cDNA library using iPLA(2)beta cDNA as bait.
      Cloning CaMKIIbeta cDNA from a rat islet library revealed that one dominant
      CaMKIIbeta isoform mRNA is expressed by adult islets and is not observed in brain
      or neonatal islets and that there is high conservation of the isoform expressed
      by rat and human beta-cells. Binary two-hybrid assays using DNA encoding this
      isoform as bait and iPLA(2)beta DNA as prey confirmed interaction of the enzymes,
      as did assays with CaMKIIbeta as prey and iPLA(2)beta bait. His-tagged CaMKIIbeta
      immobilized on metal affinity matrices bound iPLA(2)beta, and this did not
      require exogenous calmodulin and was not prevented by a calmodulin antagonist or
      the Ca(2+) chelator EGTA. Activities of both enzymes increased upon their
      association, and iPLA(2)beta reaction products reduced CaMKIIbeta activity. Both
      the iPLA(2)beta inhibitor bromoenol lactone and the CaMKIIbeta inhibitor KN93
      reduced arachidonate release from INS-1 insulinoma cells, and both inhibit
      insulin secretion. CaMKIIbeta and iPLA(2)beta can be coimmunoprecipitated from
      INS-1 cells, and forskolin, which amplifies glucose-induced insulin secretion,
      increases the abundance of the immunoprecipitatable complex. These findings
      suggest that iPLA(2)beta and CaMKIIbeta form a signaling complex in beta-cells,
      consistent with reports that both enzymes participate in insulin secretion and
      that their expression is coinduced upon differentiation of pancreatic progenitor
      to endocrine progenitor cells.

PMID- 15576377
TI  - Serum amyloid A binding to CLA-1 (CD36 and LIMPII analogous-1) mediates serum
      amyloid A protein-induced activation of ERK1/2 and p38 mitogen-activated protein
      kinases.
AB  - Serum amyloid A protein (SAA) is an acute-phase reactant, known to mediate pro
      inflammatory cellular responses. This study reports that CLA-1 (CD36 and LIMPII
      Analogous-1; human orthologue of the Scavenger Receptor Class B Type I (SR-BI))
      mediates SAA uptake and downstream SAA signaling. Flow cytometry experiments
      revealed more than a 5-fold increase of Alexa-488 SAA uptake in HeLa cells stably
      transfected with CLA-1. Alexa 488-HDL uptake directly correlated with SAA uptake
      when determined in several CLA-1 stably transfected HeLa cell clones expressing
      various levels of CLA-1. SAA directly binds to CLA-1 as determined by cross
      linking and colocalization of anti-CLA-1 antibody with SAA. SAA was co
      internalized with transferrin to the endocytic recycling compartment pointing to
      a potential site of SAA metabolism. Alexa-488 SAA uptake in the CLA-1
      overexpressing HeLa cells, as well as in THP-1 monocyte cell line, can be
      efficiently blocked by unlabeled SAA, high density lipoprotein, and other CLA-1
      ligands. At the same time, markedly enhanced levels of phosphorylation of the
      mitogen-activated protein kinases (MAPKs), ERK1/2, and p38, were observed in
      cells stably transfected with CLA-1 cells following SAA stimulation when compared
      with mock transfected cells. The levels of the SAA-induced interleukin-8 (IL-8)
      secretion by CLA-1-overexpressing cells also significantly exceeded (5- to 10
      fold) those detected for control cells. Synthetic amphipathic peptides possessing
      a structural alpha-helical motif inhibited SAA-induced activation of both MAPKs
      and IL-8 secretion in THP-1 cells. The results of this study demonstrate for the
      first time that CLA-1 functions as an endocytic SAA receptor and is involved in
      SAA-mediated cell signaling events associated with the immune-related and
      inflammatory effects of SAA.

PMID- 15576378
TI  - Distinct signaling pathways are involved in leukosialin (CD43) down-regulation,
      membrane blebbing, and phospholipid scrambling during neutrophil apoptosis.
AB  - Although leukosialin (CD43) membrane expression decreases during neutrophil
      apoptosis, the CD43 molecule, unexpectedly, is neither proteolyzed nor
      internalized. We thus wondered whether it could be shed on bleb-derived membrane
      vesicles. Membrane blebbing is a transient event, hardly appreciated during the
      asynchronous, spontaneous apoptosis of neutrophils. Cell pre-synchronization at
      15 degrees C made it possible to observe numerous blebbing neutrophils for a
      short 1-h period at 37 degrees C. CD43 down-regulation co-occurred with the
      blebbing stage and phosphatidylserine externalization, shortly after mitochondria
      depolarization and before nuclear condensation. Blebs detaching from the cell
      body were observed by time lapse fluorescence microscopy, and the release of bleb
      derived vesicles was followed by flow cytometry. Phosphatidylserine
      externalization required caspases and protein kinase C (PKC) but not the myosin
      light chain kinase (MLCK). By contrast, bleb formation and release was caspase-
      and PKC-independent but required an active MLCK, whereas CD43 down-regulation
      involved caspases but neither PKC nor MLCK. Furthermore, CD43 appeared mostly
      excluded from membrane blebs by electron microscopy. Thus, CD43 down-regulation
      does not result from the release of bleb-derived vesicles. Ultracentrifugation of
      apoptotic cell supernatants made it possible to recover <1 microM microparticles,
      which contained the entire CD43 molecule. These microparticles expressed
      neutrophil membrane markers such as CD11b, CD66b, and CD63, together with CD43.
      In conclusion, we show that the three early membrane events of apoptosis, namely
      blebbing, phosphatidylserine externalization, and CD43 down-regulation, result
      from different signaling pathways and can occur independently from one another.
      CD43 down-regulation results from the shedding of microparticles released during
      apoptosis but unrelated to the blebbing.

PMID- 15576379
TI  - Distinct roles for the linker region tyrosines of Syk in FcepsilonRI signaling in
      primary mast cells.
AB  - Stimulation of FcepsilonRI, the high affinity IgE receptor of mast cells results
      in the rapid binding of the Syk tyrosine kinase to cytoplasmic domains of
      FcepsilonRI and to its subsequent activation. Syk plays an essential role in
      signal transduction from FcepsilonRI as shown by Syk-deficient mast cells, which
      are defective in receptor-induced degranulation, cytokine synthesis, and
      intracellular pathways. However the mechanism by which Syk activates these
      pathways remains unclear. Activation of Syk is associated with its
      phosphorylation on several tyrosine residues, including the linker tyrosines
      Tyr317, Tyr342, and Tyr346. These residues have been proposed to play important
      roles in the transduction of signals by binding to other signaling proteins. To
      test these hypotheses in primary murine mast cells, we used retroviral infection
      of Syk-deficient mast cells to generate cells expressing Syk proteins bearing
      mutations in the linker tyrosines. We show that Tyr342 and Tyr346 contribute
      positively to the function of Syk and have both overlapping as well as distinct
      functions. Mutations in either Tyr342 or Tyr346 alone had no effect on
      FcepsilonRI-induced degranulation or calcium flux, whereas mutation of both
      residues caused a significant reduction in both pathways. In contrast,
      phosphorylation of PLCgamma1, PLCgamma2, and Vav1 was strongly decreased by a
      mutation in Tyr342 alone, whereas phosphorylation of ERK and Akt was more
      dependent on Tyr346. Finally we show that Tyr317 functions as a negative
      regulatory site and that its mutation can partially compensate for the loss of
      both Tyr342 and Tyr346.

PMID- 15576380
TI  - Cell cycle-mediated regulation of smooth muscle alpha-actin gene transcription in
      fibroblasts and vascular smooth muscle cells involves multiple adenovirus E1A
      interacting cofactors.
AB  - Expression of smooth muscle alpha-actin in growth factor-induced myofibroblasts
      and in differentiated vascular smooth muscle cells is transcriptionally
      controlled by multiple positive or negative trans-acting factors interacting with
      distinct cis-elements in the 5'-flanking region of the gene. Because none of the
      transcriptional regulators reported to date is smooth muscle cell- or
      myofibroblast-specific per se, the dynamic interplay among many factors
      interacting at specific sites along the promoter appears to be a signature
      feature of smooth muscle alpha-actin gene regulation in these cell types. Herein,
      the ability of the adenovirus E1A 12 S protein to bind and functionally
      inactivate specific cell regulatory factors has been exploited to identify
      several previously unknown coactivators of the mouse smooth muscle alpha-actin
      promoter in rodent fibroblasts and vascular smooth muscle cells. In transient
      cotransfection assays, ectopic expression of wild type E1A suppressed promoter
      activity in a dose- and cis-element-dependent manner. In asynchronous cells, N
      terminal E1A mutants defective in CREB-binding protein (CBP) and p300 binding
      capacity exhibited markedly reduced inhibitory activity toward a smooth muscle
      alpha-actin promoter driven by a composite TEF-1-, SRF-, and Sp1/3-regulated
      enhancer. In synchronized cells, however, a more complex mutant E1A inhibitory
      pattern indicated that collaboration between CBP/p300 and the retinoblastoma
      family of pocket proteins was required to produce a fully functional enhancer.
      Cotransfection experiments conducted with Rb(-/-) fibroblasts demonstrated the
      necessity of pRB in augmenting smooth muscle alpha-actin enhancer/promoter
      activity. Physical interaction studies with the use of purified wild type and
      mutant E1A proteins confirmed that CBP, p300, and pRB were targets of E1A binding
      in nuclear extracts of vascular smooth muscle cells and/or fibroblasts.
      Collectively, these results suggest that a repertoire of E1A-interacting
      proteins, namely CBP/p300 and pRB, serve to integrate the activities of multiple
      trans-acting factors to control smooth muscle alpha-actin gene transcription in a
      cell type- and cell cycle-dependent manner.

PMID- 15576381
TI  - Combinatorial exploration of the catalytic site of a drug-resistant dihydrofolate
      reductase: creating alternative functional configurations.
AB  - We have applied a global approach to enzyme active site exploration, where
      multiple mutations were introduced combinatorially at the active site of Type II
      R67 dihydrofolate reductase (R67 DHFR), creating numerous new active site
      environments within a constant framework. By this approach, we combinatorially
      modified all 16 principal amino acids that constitute the active site of this
      enzyme. This approach is fundamentally different from active site point mutation
      in that the native active site context is no longer accounted for. Among the 1536
      combinatorially mutated active site variants of R67 DHFR we created, we selected
      and kinetically characterized three variants with highly altered active site
      compositions. We determined that they are of high fitness, as defined by a
      complex function consisting jointly of catalytic activity and resistance to
      trimethoprim. The k(cat) and K(M) values were similar to those for the native
      enzyme. The favourable Delta(DeltaG) values obtained (ranging from -0.72 to -1.08
      kcal/mol) suggest that, despite their complex mutational pattern, no fundamental
      change in the catalytic mechanism has occurred. We illustrate that combinatorial
      active site mutagenesis can allow for the creation of compensatory mutations that
      could not be predicted and thus provides a route for more extensive exploration
      of functional sequence space than is allowed by point mutation.

PMID- 15576382
TI  - Disulfide bonds, their stereospecific environment and conservation in protein
      structures.
AB  - We studied the specificity of the non-bonded interaction in the environment of
      572 disulfide bonds in 247 polypeptide chains selected from the Protein Data
      Bank. The preferred geometry of interaction of peptide oxygen atoms is along the
      back of the two covalent bonds at the sulfur atom of half cystine. With aromatic
      residues the geometries that direct one of the sulfur lone pair of electrons into
      the aromatic pi-system are avoided; an orientation in which the sulfide plane is
      normal or inclined to the aromatic plane and on top of its edge is normally
      preferred. The importance of the S...aromatic interaction is manifested in the
      high degree of its conservation across members in homologous protein families.
      These interactions, while providing extra overall stability to the native fold
      and reducing the accessibility of the disulfide bond and thereby preventing
      exchange reactions, also set the orientation of the conserved aromatic rings for
      further interactions and binding to another molecule. The conformational features
      and the mode of interactions of disulfide bridges should be useful for molecular
      design and protein engineering experiments.

PMID- 15576383
TI  - The impact of treatment experiences on the course of infertility distress in male
      patients.
AB  - BACKGROUND: Previous research on infertile males has delivered equivocal findings
      on the course of infertility distress in males. The present longitudinal study
      examines whether there are differentials associated with specific treatment
      experiences (i.e. duration of treatment, the diagnosis received, and treatment
      failure of assisted reproductive technologies). METHODS: The sample consisted of
      118 patients who twice visited an andrology clinic on their own initiative for
      fertility work-ups. Baseline and follow-up examinations were > or = 6 months
      apart. Prior to each fertility work-up, patients completed a questionnaire
      assessing distress due to infertility. RESULTS: No uniform course of distress
      could be detected. A significant interaction between treatment experiences
      indicated that distress rises significantly only in those patients who were in
      treatment > or = 17 months and experienced treatment failure between the first
      and the second psychological evaluation. For the diagnosis of male infertility,
      however, neither a direct nor an indirect impact was identified. CONCLUSION: The
      present study indicates that the interaction of specific treatment experiences is
      associated with changes in distress of infertile males.

PMID- 15576384
TI  - Prediction of outcomes of assisted reproduction treatment using the calcium
      ionophore-induced acrosome reaction.
AB  - BACKGROUND: Sperm concentration and motility are poor predictors of the outcome
      of intrauterine insemination (IUI), hysteroscopic intratubal insemination (HIT),
      or complete fertilization failure (CFF) in conventional IVF. We investigated
      whether the calcium ionophore-induced acrosome reaction (AR) constitutes an
      additional indicator of CFF and pregnancy that is independent of these semen
      parameters. METHODS: Infertile couples with no female factor (n=388) and women
      with tubal obstruction (n=32) were studied: IVF (n=133), ICSI (n=72), HIT (n=245)
      and IUI (n=61). The percentage of acrosome-reacted sperm in relation to viable
      sperm was calculated. Receiver operating characteristic curve and multiple
      logistic regression analyses were used to determine threshold values and the best
      predictor for CFF and pregnancy. RESULTS: Threshold values of AR for predicting
      CFF in IVF and pregnancy in IVF and HIT + IUI were 21, 26 and 22% respectively.
      These values were independent of the conventional semen analysis parameters. CFF
      was lower (2 versus 20%; P<0.01) and the pregnancy rate was higher (46 versus 24%
      P<0.05) for those with AR >21% in IVF. CFF and pregnancy rate in ICSI did not
      differ according to AR. Pregnancy rate was higher for those with an AR >22% for
      HIT + IUI (23 versus 11% P<0.01). CONCLUSIONS: Ionophore-induced AR appears to be
      a useful indicator in addition to routine semen analysis for selection of
      patients for treatment with appropriate assisted reproduction procedure.

PMID- 15576385
TI  - Maternal recreational physical activity is associated with plasma leptin
      concentrations in early pregnancy.
AB  - BACKGROUND: A limited amount of literature suggests that plasma leptin
      concentrations are reduced with habitual physical activity in men and non
      pregnant women. We investigated the relationship between maternal physical
      activity and plasma leptin during early pregnancy. METHODS: The study population
      included 879 normotensive, non-diabetic pregnant women who reported physical
      activity type, frequency, and duration in early pregnancy. Plasma leptin,
      measured in blood samples collected <16 weeks gestation, were determined using
      enzyme immunoassays. Weekly duration (h/week) and energy expended on recreational
      physical activity [metabolic equivalent score (MET)-h/week] were categorized by
      tertiles among active women. Physical activity intensity was categorized as none,
      moderate (<6 MET) and vigorous (> or =6 MET). Differences in leptin
      concentrations across categories were estimated using linear regression
      procedures. RESULTS: Mean leptin was 5.8 ng/ml lower among active versus inactive
      women (P=0.001). Mean leptin was lower among women in the highest levels (>12.8
      h/week) of time performing physical activity (-8.1 ng/ml, P<0.001) and energy
      expenditure (>70.4 MET-h/week) (-8.3 ng/ml, P=0.001) compared with inactive
      women. Leptin was inversely associated with the intensity of physical activity.
      CONCLUSIONS: Our findings are consistent with other reports suggesting an
      independent inverse relationship between habitual physical activity and leptin
      concentrations. Our findings extend the literature to include pregnant women.

PMID- 15576386
TI  - The involvement of the interstitial Cajal cells and the enteric nervous system in
      bowel endometriosis.
AB  - BACKGROUND: Our aim was to investigate the relationships between gastrointestinal
      symptoms and histological findings in women with bowel endometriosis. METHODS:
      The gastrointestinal symptoms of 362 women with endometriosis were classified
      according to the subgroups of the Rome II criteria. All visible endometriotic
      lesions of the bowel were removed; the patients were prospectively followed up
      for 2 years. The interstitial Cajal cells (ICC) and the enteric nervous system
      were immunohistochemically evaluated. RESULTS: Sixty-eight (18.8%, 95% CI 14.9
      23.2) women had bowel lesions. The endometriotic lesions infiltrated the serosal
      layer and surrounding connective tissue in 45 cases; the subserous plexus in 11
      cases; the Auerbach plexus in eight cases; the Meissner plexus in four cases.
      Whenever the subserous plexus was interrupted by the endometriotic lesions, the
      ICC were damaged. All women with endometriotic lesions reaching at least the
      subserous plexus reported bowel complaints. The level of infiltration into the
      bowel wall was correlated with severity of symptoms. Removal of lesions resulted
      in improvement of symptoms. CONCLUSIONS: Endometriosis-induced damage of ICC,
      even before muscular infiltration, may cause bowel symptoms.

PMID- 15576387
TI  - Effect of 'PC Game Room' use and polycyclic aromatic hydrocarbon exposure on
      plasma testosterone concentrations in young male Koreans.
AB  - BACKGROUND: 'PC Game Rooms' were first popularized in Korea, although the concept
      is now becoming popular worldwide. PC Game Rooms provide users with high
      performance PC connected to the high-speed internet, and access to computer
      games. However, PC Game Room users are exposed to various hazardous agents such
      as cigarette smoke in a confined environment, and thus it is likely that
      excessive PC Game Room use involves abnormal exposure to polycyclic aromatic
      hydrocarbons (PAH) as well as being associated with disturbed sleep or circadian
      rhythm. METHODS: In this cross-sectional study, the exposure to PAH was evaluated
      by measuring urinary 1-hydroxypyrene (1-OHP) and 2-naphthol. The correlations
      between PC Game Room use and PAH exposure and plasma testosterone and LH levels
      were analysed in 208 young male Koreans. RESULTS: Urinary 1-OHP concentrations
      increased (P = 0.0001) and plasma testosterone levels decreased (P = 0.0153)
      significantly with increased duration of PC Game Room use. Correlation analysis
      showed that plasma testosterone concentrations were significantly negatively
      correlated with urinary 1-OHP (r = -0.22, P = 0.0012) and 2-naphthol (r = -0.15,
      P = 0.0308) concentrations. Moreover, these associations persisted after
      adjusting for other independent variables. However, the duration of PC Game Room
      use itself was not found to be an independent significant determinant of plasma
      testosterone level. Rather, PC Game Room use increased PAH exposure, which
      decreased plasma testosterone level. The younger age group (15-19 years) showed a
      more prominent decrease in plasma testosterone concentrations with increasing
      duration of PC Game Room use than the older age group (20-24 years) (r2 = 0.355,
      P = 0.0301 versus r2 = 0.213, P = 0.0001). CONCLUSIONS: These results imply that
      the excessive use of PC Game Rooms is related to an adverse impact on sex
      hormonal status in young male Koreans via PAH exposure. This effect was more
      prominent in the younger age group.

PMID- 15576388
TI  - Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and
      profile.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur
      either as an early (early onset) or a late pattern (late onset). This
      observational study was designed to identify whether the onset pattern of OHSS is
      associated with the occurrence of pregnancy and the early pregnancy outcome.
      METHODS: Among 4376 consecutive IVF/ICSI cycles, 113 patients were hospitalized
      for OHSS after IVF/ICSI treatment and were included in the study. The setting was
      the Dutch-speaking Brussels Free University Hospital, between June 2000 and
      September 2002. RESULTS: Early OHSS occurred in 53 patients, and late OHSS
      complicated 60 patients. A total of 96.7% of the late OHSS cases occurred in a
      pregnancy cycle and were more likely to be severe than the early cases (P <
      0.05). Although in the early group there initially was a 41.5% positive HCG rate
      per cycle, the clinical pregnancy rate fell to 28.3% as a result of a
      significantly (P < 0.05) increased preclinical pregnancy loss rate compared with
      the non-OHSS patients (31.8 versus 88.3%, respectively). The ongoing pregnancy
      rate per cycle was 14.4% in the early and 26.4% in the late group. Multiple
      pregnancy rates were high in both groups (40 and 45.5%, respectively), but only
      in the late group did the incidence reach significance compared with the non-OHSS
      population (45.5 versus 29.1%, P = 0.02). Estradiol levels and number of
      follicles on the day of HCG were significantly higher in the early OHSS group.
      However, there was no difference in estradiol values on the day of hospital
      admittance between the two groups. In addition, the number of follicles on the
      day of HCG administration appears to be a better prognostic indicator for the
      occurrence of severe OHSS than the estradiol values (87% of the severe cases had
      > or = 14 or follicles of a diameter > or = 11 mm, whereas only 50% of them had
      an estradiol value > or = 3000 ng/l). CONCLUSIONS: The early OHSS pattern is
      associated with exogenously administered HCG and a higher risk of preclinical
      miscarriage, whereas late OHSS may be closely associated with the conception
      cycles, especially multiple pregnancies, and is more likely to be severe. Further
      clarification of these two different clinical entities could have implications
      for research protocols as well as for preventive and management strategies for
      OHSS.

PMID- 15576390
TI  - Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up
      protocol during controlled ovarian stimulation in normogonadotrophic women with
      initial inadequate ovarian response to rFSH. A multicentre, prospective,
      randomized controlled trial.
AB  - BACKGROUND: In approximately 12-14% of young normogonadotrophic women treated
      with a depot GnRH agonist long protocol, the initial ovarian response to
      recombinant human FSH (rFSH) can be suboptimal. We have tested the hypothesis
      that these women may benefit from recombinant human LH (rLH) supplementation in a
      multicentre, prospective, randomized trial compared with patients treated with an
      rFSH step-up protocol. METHODS: A total of 260 young normogonadotrophic women
      undergoing controlled ovarian stimulation with a GnRH agonist long protocol for
      IVF/ICSI were enrolled. The starting dose of rFSH was 225 IU. One hundred and
      thirty patients with serum estradiol levels <180 pg/ml and with at least six
      follicles with a mean diameter >5 mm but none >10 mm on both day 5 and day 8 of
      stimulation were randomly allocated to two groups. From the eighth day of
      stimulation, women in group A (n=65) received 150 IU of rLH in addition to rFSH,
      while those in group B (n=65) had an increase of 150 IU in the daily dose of rFSH
      (step-up protocol). One hundred and thirty normally responding women continued
      monotherapy with rFSH and served as a further control population (group C).
      RESULTS: The mean number of cumulus-oocyte complexes retrieved in group A (9.0+/
      4.3) was significantly higher (P<0.01) compared with group B (rFSH 6.1+/-2.6) but
      significantly lower compared with group C (10.49+/-3.7, P<0.05). Implantation and
      pregnancy rates were significantly lower (P<0.05) in the rFSH step-up group (10.5
      and 29.3% respectively) when compared with normal responders (18.1 and 47.3%
      respectively). CONCLUSIONS: rLH supplementation is more effective than increasing
      the dose of rFSH in terms of ovarian outcome in patients with an initial
      inadequate ovarian response to rFSH alone.

PMID- 15576391
TI  - Tryptase inhibits motility of human spermatozoa mainly by activation of the
      mitogen-activated protein kinase pathway.
AB  - BACKGROUND: We previously localized protease-activated receptor 2 (PAR-2) on
      human spermatozoa and demonstrated that activation of PAR-2 by the mast cell (MC)
      product tryptase inhibits sperm motility. Importantly, tryptase-secreting MCs are
      encountered in the male and female genital tract, implying that MC-spermatozoa
      interactions may be as yet unrecognized factors affecting sperm fertilizing
      ability. In order to elucidate how tryptase via activation of PAR-2 acts in human
      spermatozoa, we studied intracellular signal transduction events. METHODS AND
      RESULTS: Impairment of sperm motility by tryptase was not dependent on the
      presence of extracellular Ca2+ and tryptase did not alter intracellular Ca2+
      levels. Pre-incubation with pertussis toxin (PTX) failed to prevent tryptase
      effects on sperm motility. Western blot analyses revealed that tryptase increased
      phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2, an effect
      which was blocked by the MAPK pathway inhibitor PD98059. Pre-treatment of
      spermatozoa with this inhibitor also blocked the inhibtion of sperm motility
      evoked by tryptase. CONCLUSIONS: These results indicate that tryptase acts via
      the ERK1/2 pathway to inhibit motility of human spermatozoa.

PMID- 15576392
TI  - Endometrial and subendometrial blood flow measured by three-dimensional power
      Doppler ultrasound in patients with small intramural uterine fibroids during IVF
      treatment.
AB  - BACKGROUND: The impact of intramural fibroids on the success of IVF treatment is
      controversial and the mechanisms leading to poor treatment outcomes remain
      unknown. We compared endometrial and subendometrial blood flow between women with
      and without intramural fibroids during IVF treatment. METHODS: Three-dimensional
      (3D) ultrasound examination with power Doppler was performed on the day of oocyte
      retrieval in 50 patients with intramural fibroids not distorting the uterine
      cavity and in 50 matched controls to measure endometrial thickness, uterine
      pulsatility index (PI)/resistance index (RI), endometrial volume and
      vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of
      endometrial and subendometrial regions. Smokers, patients with serum estradiol
      concentrations > or =20,000 pmol/l on the day of HCG and previous history of
      myomectomy were excluded. RESULTS: Endometrial thickness and pattern, averaged
      uterine PI and RI and endometrial and subendometrial VI/FI/VFI were similar
      between the fibroid group and the control group. There was no correlation between
      the total volume of fibroids and endometrial and subendometrial 3D power Doppler
      flow indices in the fibroid group. CONCLUSION: Endometrial and subendometrial 3D
      power Doppler flow indices were similar in patients with and without small
      intramural fibroids.

PMID- 15576393
TI  - A multi-centre cohort study of the physical health of 5-year-old children
      conceived after intracytoplasmic sperm injection, in vitro fertilization and
      natural conception.
AB  - BACKGROUND: Over a million children have been born from assisted conception
      worldwide. Newer techniques being introduced appear less and less 'natural', such
      as intracytoplasmic sperm injection (ICSI), but there is little information on
      these children beyond the neonatal period. METHODS: 540 ICSI conceived 5-year-old
      children from five European countries were comprehensively assessed, along with
      538 matched naturally conceived children and 437 children conceived with standard
      IVF. RESULTS: Of the 540 ICSI children examined, 63 (4.2%) had experienced a
      major congenital malformation. Compared with naturally conceived children, the
      odds of a major malformation were 2.77 (95% CI 1.41-5.46) for ICSI children and
      1.80 (95% CI 0.85-3.81) for IVF children; these estimates were little affected by
      adjustment for socio-demographic factors. The higher rate observed in the ICSI
      group was due partially to an excess of malformations in the (boys') urogenital
      system. In addition, ICSI and IVF children were more likely than naturally
      conceived children to have had a significant childhood illness, to have had a
      surgical operation, to require medical therapy and to be admitted to hospital. A
      detailed physical examination revealed no further substantial differences between
      the groups, however. CONCLUSIONS: Singleton ICSI and IVF 5-year-olds are more
      likely to need health care resources than naturally conceived children.
      Assessment of singleton ICSI and IVF children at 5 years of age was generally
      reassuring, however, we found that ICSI children presented with more major
      congenital malformations and both ICSI and IVF children were more likely to need
      health care resources than naturally conceived children. Ongoing monitoring of
      these children is therefore required.

PMID- 15576394
TI  - The effect of combination therapy with metformin and combined oral contraceptives
      (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and
      lipids in PCOS patients.
AB  - BACKGROUND: Neither oral contraceptives (COC) nor metformin are an optimal
      modality for the long-term treatment of polycystic ovary syndrome (PCOS). The aim
      of this study was to evaluate whether a combination of both is beneficial over
      COC monotherapy. METHODS: Altogether, 30 women were included in the study and 28
      finished the protocol. The patients were randomly assigned to two groups treated
      with either COC (COC group) or COC and metformin (1500 mg/day) (METOC group) for
      6 months. Anthropometric parameters, androgens, lipids, fasting insulin, glucose
      and sex hormone binding globulin (SHBG) concentrations were measured before and
      at the end of the sixth cycle of treatment. The insulin sensitivity index was
      evaluated using the euglycaemic clamp. RESULTS: There were no significant changes
      in anthropometric parameters, fasting glucose or insulin sensitivity in either
      group. Total testosterone, free androgen index, androstenedione and
      dehydroepiandrosterone decreased and SHBG increased significantly in both groups.
      When comparing the effect of both treatments, only a more pronounced decrease in
      free androgen index was found in the METOC group. CONCLUSIONS: Adding metformin
      slightly modified the treatment effect of COC, causing a more significant
      decrease in the free androgen index but having no additional positive impact on
      lipids, insulin sensitivity, SHBG or testosterone. The available data do not
      offer enough evidence to advocate the standard use of combined treatment in PCOS.
      Whether the combination might be beneficial for specific subgroups of patients is
      of further interest.

PMID- 15576395
TI  - Chromosomal instability in two siblings with gonad deficiency: case report.
AB  - Non-random de novo autosomal chromosomal rearrangements have not been shown to
      cause exocrine or gonadal dysfunction. We report on two siblings, a brother and a
      sister, both with de novo chromosomal rearrangements and gonadal deficiency
      including premature ovarian failure. They had normal phenotypes without
      additional manifestations of known chromosomal breakage syndromes (except for the
      gonadal dysfunction) and normal alpha-fetoprotein dosage level. The association
      of sperm abnormalities in the brother and ovarian dysfunction in the sister
      suggested an increased spontaneous chromosomal instability. Since the co
      occurrence of chromosomal anomalies and reproductive failures may not be
      coincidental, we performed repeated chromosomal analysis of peripheral blood
      lymphocytes prior to proposing ICSI for IVF (for the brother). In both sibs,
      infertility was associated with random and non-random de novo autosomal
      chromosomal abnormalities. We discuss the possible relationship between these
      unusual clinical and cytogenetic features and their potential links to ataxia
      telangiectasia.

PMID- 15576396
TI  - Sperm retrieval techniques in rats with suppressed spermatogenesis by
      experimental cryptorchidism.
AB  - OBJECTIVE: Our aim was to assess the suppression of spermatogenesis and sperm
      retrieval rate after testicular sperm extraction (TESE) or testicular sperm
      aspiration (TESA) in adult rats with surgically induced cryptorchidism. METHODS:
      Adult rats were submitted to TESE and TESA procedures after 15 days of induced
      cryptorchidism. After spermatozoa retrieval, the testicles were extracted,
      weighed and a morphological analysis by conventional light microscopy was done.
      The numbers of spermatozoa retrieved in both TESA and TESE were rated and
      compared. RESULTS: Histological analysis of the testicles revealed Sertoli cell
      only syndrome in 60% of the testicles, and maturation arrest in the remaining
      cryptorchid testicles. Significant differences were seen in the number of
      spermatozoa retrieved (P < 0.05) between cryptorchidic and control rats. When
      sperm retrieval techniques were compared, no differences were detected in the
      number of spermatozoa obtained (P > 0.05). CONCLUSIONS: It seems that a 15 day
      period of cryptorchidism is enough to induce spermatogenesis disorders. No
      differences were detected in the number of spermatozoa retrieved in the right or
      left testicles, irrespective of the testicular pole. Furthermore, and even more
      importantly, no differences in the retrieval rate were seen between the two
      techniques.

PMID- 15576397
TI  - Morphological events in the primate endometrium in the presence of a
      preimplantation embryo, detected by the serum preimplantation factor bioassay.
AB  - BACKGROUND: Hormonal modulation of the endometrium towards receptivity is well
      established; however, the role of embryonic stimuli in modulation of the
      endometrium prior to implantation, especially in primates, is unknown. The aim of
      the present study was to evaluate the endometrial histology when the embryo was
      present in its vicinity prior to implantation. METHODS: Preimplantation factor
      (PIF) bioassay was used as a tool to detect the presence of an embryo in the
      uterine lumen of mated bonnet monkeys (Macaca radiata) (n=9). The control group
      comprised seven non-mated animals. The specificity of the PIF bioassay for the
      presence of an embryo was tested by studies in pregnant humans and monkeys. The
      effects of embryonic stimuli on the endometrial morphology were analysed by
      routine haematoxylin-eosin staining. The expressions of CD34, an endothelial cell
      marker, alpha-smooth muscle actin (alpha-SMA), a marker for blood vessel
      maturation, and prolactin, a marker of endometrial decidualization, were studied
      by immunohistochemistry. RESULTS: That PIF is embryo specific was established by
      its presence in sera of pregnant humans, monkeys and also in embryo culture
      media. Six mated bonnet monkeys were found to be PIF positive. Morphologically,
      the endometria from these PIF-positive animals showed the presence of the pre
      epithelial plaque reaction, increased angiogenesis and stromal compaction. The
      significantly increased number of CD34- and alpha-SMA-positive blood vessels
      (P<0.05) in the endometria of PIF-positive animals indicated increased
      angiogenesis in response to embryonic stimuli. The endometrial expression of
      immunoreactive prolactin was also significantly increased (P<0.05) in the PIF
      positive animals, indicating decidualization. CONCLUSIONS: Using PIF as a marker
      to detect early pregnancy in bonnet monkeys, we have shown that the embryo
      induces a pre-epithelial plaque type of reaction, increased angiogenesis and
      decidual reaction in the endometrium prior to implantation.

PMID- 15576398
TI  - Identification of genes expressed in primate primordial oocytes.
AB  - BACKGROUND: The factors involved in oocyte survival and transition from
      quiescence to the growing phenotype remain unknown. Herein we report genes that
      are differentially expressed in the primordial oocyte revealed by DNA arrays.
      METHODS: Primordial oocytes were captured selectively in rhesus monkey ovary
      sections using laser capture microdissection. The RNA was extracted and amplified
      in two rounds by T7-based linear RNA amplification, fluorescence labelled and
      then hybridized to human cDNA arrays containing 7680 elements. RNA from human
      placenta served as a reference sample. RESULTS: Ninety-five genes were found to
      be consistently expressed at a higher level in primordial oocytes. Expression of
      several of these genes in the oocyte has been reported before, e.g. deleted in
      azoospermia (DAZ), prohibitin and transglutaminase 2. Oocyte expression of
      several novel transcripts revealed on array hybridization, such as gene 33,
      ubiquitin-conjugating enzyme E2A, G1 to S phase transition 1, growth arrest and
      DNA damage-inducible (GADD), and dendritic cell-derived ubiquitin-like protein
      (DC-UbP) was confirmed by in situ hybridization. Some array-identified gene
      products [integrin beta3, alpha-tubulin, regulatory telomere elongation protein
      (RAP1) and cellular repressor of EIA-stimulated genes (CREG protein)] were
      detected in human oocytes by immunofluorescence. Bioinformatic analysis of the
      oocyte-enriched transcripts reveals a functional profile summarized as follows:
      cell cycle (14%); transporter (13%); signal transduction (10%); cytoskeletal
      (7%); transcription factor (5%); immune response (5%); apoptosis-related (5%);
      RNA processing (5%); and the remainder of miscellaneous categories. CONCLUSIONS:
      These observations may contribute to the elucidation of molecular pathways
      involved in oocyte survival and maturation.

PMID- 15576399
TI  - Smad1, beta-catenin and Tcf4 associate in a molecular complex with the Myc
      promoter in dysplastic renal tissue and cooperate to control Myc transcription.
AB  - Renal dysplasia, the major cause of childhood renal failure in humans, arises
      from perturbed renal morphogenesis and molecular signaling during embryogenesis.
      Recently, we discovered induction of molecular crosstalk between Smad1 and beta
      catenin in the TgAlk3QD mouse model of renal medullary cystic dysplasia. Our
      finding that Myc, a Smad and beta-catenin transcriptional target and effector of
      renal epithelial dedifferentiation, is misexpressed in dedifferentiated
      epithelial tubules provided a basis for investigating coordinate transcriptional
      control by Smad1 and beta-catenin in disease. Here, we report enhanced
      interactions between a molecular complex consisting of Smad1, beta-catenin and
      Tcf4 and adjacent Tcf- and Smad-binding regions located within the Myc promoter
      in TgAlk3QD dysplastic renal tissue, and Bmp-dependent cooperative control of Myc
      transcription by Smad1, beta-catenin and Tcf4. Analysis of nuclear extracts
      derived from TgAlk3QD and wild-type renal tissue revealed increased levels of
      Smad1/beta-catenin molecular complexes, and de novo formation of chromatin
      associated Tcf4/Smad1 molecular complexes in TgAlk3QD tissues. Analysis of a 476
      nucleotide segment of the 1490 nucleotide Myc genomic region upstream of the
      transcription start site demonstrated interactions between Tcf4 and the Smad
      consensus binding region and associations of Smad1, beta-catenin and Tcf4 with
      oligo-duplexes that encode the adjacent Tcf- and Smad-binding elements only in
      TgAlk3QD tissues. In collecting duct cells that express luciferase under the
      control of the 1490 nucleotide Myc genomic region, Bmp2-dependent stimulation of
      Myc transcription was dependent on contributions by each of Tcf4, beta-catenin
      and Smad1. These results provide novel insights into mechanisms by which
      interacting signaling pathways control transcription during the genesis of renal
      dysplasia.

PMID- 15576400
TI  - Chx10 repression of Mitf is required for the maintenance of mammalian
      neuroretinal identity.
AB  - During vertebrate eye development, the cells of the optic vesicle (OV) become
      either neuroretinal progenitors expressing the transcription factor Chx10, or
      retinal pigment epithelium (RPE) progenitors expressing the transcription factor
      Mitf. Chx10 mutations lead to microphthalmia and impaired neuroretinal
      proliferation. Mitf mutants have a dorsal RPE-to-neuroretinal phenotypic
      transformation, indicating that Mitf is a determinant of RPE identity. We report
      here that Mitf is expressed ectopically in the Chx10(or-J/or-J) neuroretina (NR),
      demonstrating that Chx10 normally represses the neuroretinal expression of Mitf.
      The ectopic expression of Mitf in the Chx10(or-J/or-J) NR deflects it towards an
      RPE-like identity; this phenotype results not from a failure of neuroretinal
      specification, but from a partial loss of neuroretinal maintenance. Using Chx10
      and Mitf transgenic and mutant mice, we have identified an antagonistic
      interaction between Chx10 and Mitf in regulating retinal cell identity. FGF
      (fibroblast growth factor) exposure in a developing OV has also been shown to
      repress Mitf expression. We demonstrate that the repression of Mitf by FGF is
      Chx10 dependent, indicating that FGF, Chx10 and Mitf are components of a pathway
      that determines and maintains the identity of the NR.

PMID- 15576401
TI  - Different thresholds of fibroblast growth factors pattern the ventral foregut
      into liver and lung.
AB  - Cell fate and morphogenesis within the embryo is dependent upon secreted
      molecules that transduce signals between neighboring tissues. Reciprocal
      mesenchymal-epithelial interactions have proven essential during branching
      morphogenesis and cell differentiation within the lung; however, the interactions
      that result in lung specification from the foregut endoderm, prior to lung bud
      formation, are poorly understood. In this study, we investigate the tissue
      requirements and signals necessary for specification of a pulmonary cell fate
      using embryo tissue explants. We show that NKX2.1, an early transcription factor
      crucial for lung development, is expressed in the ventral foregut endoderm
      shortly after albumin and Pdx1, early markers of the liver and pancreas lineages,
      respectively. Similar to hepatic specification, direct contact of cardiac
      mesoderm with ventral endoderm is required to induce in vitro expression of
      NKX2.1 and downstream lung target genes including surfactant protein C and Clara
      cell secretory protein. In the absence of cardiac mesoderm, ventral foregut
      endoderm explants respond to exogenous fibroblast growth factor (FGF) 1 and FGF2
      in a dose-dependent manner, with lower concentrations activating liver specific
      genes and higher concentrations activating lung specific genes. This signaling
      appears to be instructive, as the prospective dorsal midgut endoderm, which
      predominantly gives rise to the intestinal tract, is competent to respond to FGFs
      by inducing NKX2.1. Furthermore, the temporal expression and selective inhibition
      of FGF receptors 1 and 4 present within the endoderm implies that signaling
      through FGFR4 is involved in specifying lung versus liver. Together, the findings
      suggest that a concentration threshold of FGFs emanating from the cardiac
      mesoderm are involved in patterning the foregut endoderm.

PMID- 15576402
TI  - Drosophila retained/dead ringer is necessary for neuronal pathfinding, female
      receptivity and repression of fruitless independent male courtship behaviors.
AB  - Mutations in the Drosophila retained/dead ringer (retn) gene lead to female
      behavioral defects and alter a limited set of neurons in the CNS. retn is
      implicated as a major repressor of male courtship behavior in the absence of the
      fruitless (fru) male protein. retn females show fru-independent male-like
      courtship of males and females, and are highly resistant to courtship by males.
      Males mutant for retn court with normal parameters, although feminization of retn
      cells in males induces bisexuality. Alternatively spliced RNAs appear in the
      larval and pupal CNS, but none shows sex specificity. Post-embryonically, retn
      RNAs are expressed in a limited set of neurons in the CNS and eyes. Neural
      defects of retn mutant cells include mushroom body beta-lobe fusion and
      pathfinding errors by photoreceptor and subesophageal neurons. We posit that some
      of these retn-expressing cells function to repress a male behavioral pathway
      activated by fruM.

PMID- 15576403
TI  - Growth and pattern of the mammalian neural tube are governed by partially
      overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1.
AB  - Upregulation of Patched (Ptc), the Drosophila Hedgehog (Hh) receptor in response
      to Hh signaling limits the range of signaling within a target field by
      sequestering Hh. In vertebrates, Ptch1 also exhibits ligand-dependent
      transcriptional activation, but mutants lacking this response show surprisingly
      normal early development. The identification of Hh-interacting protein 1 (Hhip1),
      a vertebrate-specific feedback antagonist of Hh signaling, raises the possibility
      of overlapping feedback controls. We addressed the significance of feedback
      systems in sonic hedgehog (Shh)-dependent spinal cord patterning. Mouse embryos
      lacking both Ptch1 and Hhip1 feedback activities exhibit severe patterning
      defects consistent with an increased magnitude and range of Hh signaling, and
      disrupted growth control. Thus, Ptc/Ptch1-dependent feedback control of Hh
      morphogens is conserved between flies and mice, but this role is shared in
      vertebrates with Hhip1. Furthermore, this feedback mechanism is crucial in
      generating a neural tube that contains appropriate numbers of all ventral and
      intermediate neuronal cell types.

PMID- 15576404
TI  - Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
AB  - Signals that govern development of the osteoblast lineage are not well
      understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of
      proteins, is essential for osteogenesis in the endochondral skeleton during
      embryogenesis. The canonical pathway of Wnt signaling has been implicated by
      studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass
      homeostasis. In the present study we demonstrate that beta-catenin, a central
      player in the canonical Wnt pathway, is indispensable for osteoblast
      differentiation in the mouse embryo. Moreover, we present evidence that Wnt
      signaling functions downstream of Ihh in development of the osteoblast lineage.
      Finally Wnt7b is identified as a potential endogenous ligand regulating
      osteogenesis. These data support a model that integrates Hh and Wnt signaling in
      the regulation of osteoblast development.

PMID- 15576405
TI  - Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity
      of the cholesterol-modified ligand.
AB  - Previous studies have demonstrated that Disp1 function is essential for Shh and
      Ihh signaling in the mouse, and Disp1 gene dose regulates the level of Shh
      signaling activity in vivo. To determine whether Disp1 activity is required in
      Shh-producing cells for paracrine signaling in Shh target fields, we used a
      ShhGFP-Cre (here shortened to ShhCre) knock-in allele and a Disp1 conditional
      allele to knock down Disp1 activity specifically within Shh-producing cells. The
      resulting facial and neural tube phenotypes support the conclusion that the
      primary and probably exclusive role for Disp1 is within hedgehog protein
      producing cells. Furthermore, using an allele that produces N-Shh (a
      noncholesterol modified form of the Shh protein), we demonstrate that N-Shh is
      sufficient to rescue most of the early embryonic lethal defects in a Disp1-null
      mutant background. Thus, Disp1 activity is only required for paracrine hedgehog
      protein signaling by the cholesterol modified form of Shh (N-Shhp), the normal
      product generated by auto-processing of a Shh precursor protein. In both
      respects, Disp function is conserved from Drosophila to mice.

PMID- 15576406
TI  - The Hand1 and Hand2 transcription factors regulate expansion of the embryonic
      cardiac ventricles in a gene dosage-dependent manner.
AB  - The basic helix-loop-helix transcription factors Hand1 and Hand2 display dynamic
      and spatially restricted expression patterns in the developing heart. Mice that
      lack Hand2 die at embryonic day 10.5 from right ventricular hypoplasia and
      vascular defects, whereas mice that lack Hand1 die at embryonic day 8.5 from
      placental and extra-embryonic abnormalities that preclude analysis of its
      potential role in later stages of heart development. To determine the cardiac
      functions of Hand1, we generated mice harboring a conditional Hand1-null allele
      and excised the gene by cardiac-specific expression of Cre recombinase. Embryos
      homozygous for the cardiac Hand1 gene deletion displayed defects in the left
      ventricle and endocardial cushions, and exhibited dysregulated ventricular gene
      expression. However, these embryos survived until the perinatal period when they
      died from a spectrum of cardiac abnormalities. Creation of Hand1/2 double mutant
      mice revealed gene dose-sensitive functions of Hand transcription factors in the
      control of cardiac morphogenesis and ventricular gene expression. These findings
      demonstrate that Hand factors play pivotal and partially redundant roles in
      cardiac morphogenesis, cardiomyocyte differentiation and cardiac-specific
      transcription.

PMID- 15576407
TI  - Assessing the role of hematopoietic plasticity for endothelial and hepatocyte
      development by non-invasive lineage tracing.
AB  - Hematopoietic cells have been reported to convert into a number of non
      hematopoietic cells types after transplantation/injury. Here, we have used a
      lineage tracing approach to determine whether hematopoietic plasticity is
      relevant for the normal development of hepatocytes and endothelial cells, both of
      which develop in close association with blood cells. Two mouse models were
      analyzed: vav ancestry mice, in which essentially all hematopoietic cells,
      including stem cells, irreversibly express yellow fluorescent protein (YFP); and
      lysozyme ancestry mice, in which all macrophages, as well as a small subset of
      all other non-myeloid hematopoietic cells, are labeled. Both lines were found to
      contain YFP+ hepatocytes at similar frequencies, indicating that macrophage to
      hepatocyte contributions occur in unperturbed mice. However, the YFP+ hepatocytes
      never formed clusters larger than three cells, suggesting a postnatal origin. In
      addition, the frequency of these cells was very low (approximately 1 in 75,000)
      and only increased two- to threefold after acute liver injury. Analysis of the
      two mouse models revealed no evidence for a hematopoietic origin of endothelial
      cells, showing that definitive HSCs do not function as hemangioblasts during
      normal development. Using endothelial cells and hepatocytes as paradigms, our
      study indicates that hematopoietic cells are tightly restricted in their
      differentiation potential during mouse embryo development and that hematopoietic
      plasticity plays at best a minor role in adult organ maintenance and
      regeneration.

PMID- 15576408
TI  - Spermatogenesis from epiblast and primordial germ cells following transplantation
      into postnatal mouse testis.
AB  - Primordial germ cells (PGCs) are derived from a population of pluripotent
      epiblast cells in mice. However, little is known about when and how PGCs acquire
      the capacity to differentiate into functional germ cells, while keeping the
      potential to derive pluripotent embryonic germ cells and teratocarcinomas. In
      this investigation, we show that epiblast cells and PGCs can establish colonies
      of spermatogenesis after transfer into postnatal seminiferous tubules of
      surrogate infertile mice. Furthermore, we obtained normal fertile offspring by
      microinsemination using spermatozoa or spermatids derived from PGCs harvested
      from fetuses as early as 8.5 days post coitum. Thus, fetal male germ cell
      development is remarkably flexible, and the maturation process, from epiblast
      cells through PGCs to postnatal spermatogonia, can occur in the postnatal
      testicular environment. Primordial germ cell transplantation techniques will also
      provide a novel tool to assess the developmental potential of PGCs, such as those
      manipulated in vitro or recovered from embryos harboring lethal mutations.

PMID- 15576409
TI  - Retinoic acid signaling acts via Hox1 to establish the posterior limit of the
      pharynx in the chordate amphioxus.
AB  - In the invertebrate chordate amphioxus, as in vertebrates, retinoic acid (RA)
      specifies position along the anterior/posterior axis with elevated RA signaling
      in the middle third of the endoderm setting the posterior limit of the pharynx.
      Here we show that AmphiHox1 is also expressed in the middle third of the
      developing amphioxus endoderm and is activated by RA signaling. Knockdown of
      AmphiHox1 function with an antisense morpholino oligonucleotide shows that
      AmphiHox1 mediates the role of RA signaling in setting the posterior limit of the
      pharynx by repressing expression of pharyngeal markers in the posterior
      foregut/midgut endoderm. The spatiotemporal expression of these endodermal genes
      in embryos treated with RA or the RA antagonist BMS009 indicates that Pax1/9,
      Pitx and Notch are probably more upstream than Otx and Nodal in the hierarchy of
      genes repressed by RA signaling. This work highlights the potential of amphioxus,
      a genomically simple, vertebrate-like invertebrate chordate, as a paradigm for
      understanding gene hierarchies similar to the more complex ones of vertebrates.

PMID- 15576410
TI  - Selective ablation of alphav integrins in the central nervous system leads to
      cerebral hemorrhage, seizures, axonal degeneration and premature death.
AB  - Mouse embryos genetically null for all alphav integrins develop intracerebral
      hemorrhage owing to defective interactions between blood vessels and brain
      parenchymal cells. Here, we have used conditional knockout technology to address
      whether the cerebral hemorrhage is due to primary defects in vascular or neural
      cell types. We show that ablating alphav expression in the vascular endothelium
      has no detectable effect on cerebral blood vessel development, whereas deletion
      of alphav expression in central nervous system glial cells leads to embryonic and
      neonatal cerebral hemorrhage. Conditional deletion of alphav integrin in both
      central nervous system glia and neurons also leads to cerebral hemorrhage, but
      additionally to severe neurological defects. Approximately 30% of these mutants
      develop seizures and die by 4 weeks of age. The remaining mutants survive for
      several months, but develop axonal deterioration in the spinal cord and
      cerebellum, leading to ataxia and loss of hindlimb coordination. Collectively,
      these data provide evidence that alphav integrins on embryonic central nervous
      system neural cells, particularly glia, are necessary for proper cerebral blood
      vessel development, and also reveal a novel function for alphav integrins
      expressed on axons in the postnatal central nervous system.

PMID- 15576411
TI  - The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate
      neurogenesis and mediates transactivation of Ngn and NeuroD.
AB  - Chromatin remodeling complexes play crucial roles in transcription and are
      implicated in processes including cell proliferation, differentiation and
      embryonic patterning. Brg1 is the catalytic subunit of the SWI/SNF chromatin
      remodeling complex and shows neural-enriched expression. Although early lethality
      of Brg1-null mice reflects its importance in embryogenesis, this phenotype
      precluded further study of specific Brg1-dependent developmental processes. Here,
      we have identified a requirement of Brg1 for both Xenopus primary neurogenesis
      and neuronal differentiation of mammalian P19 embryonic carcinoma cells. In
      Xenopus, loss of Brg1 function did not affect neural induction or neural cell
      fate determination. However, the Sox2-positive, proliferating neural progenitor
      cell population was expanded, and expression of a terminally differentiated
      neuronal marker, N-tubulin, was diminished upon loss of Brg1 activity, suggesting
      that Brg1 is required for neuronal differentiation. The ability of the bHLH
      transcription factors Ngnr1 and NeuroD to drive neuronal differentiation was also
      abolished by loss of Brg1 function, indicating that Brg1 is essential for the
      proneural activities of Ngnr1 and NeuroD. Consistent with this, dominant-negative
      interference with Brg1 function in P19 cells suppressed neuronal differentiation
      promoted by NeuroD2, showing the requirement of Brg1 for neuronal differentiation
      is conserved in mammalian cells. Finally, we discovered that Brg1 physically
      associates with both Ngnr1 and NeuroD and that interference with Brg1 function
      blocks Neurogenin3- and NeuroD2-mediated reporter gene transactivation. Together,
      our results demonstrate that Brg1 (and by inference the SWI/SNF complex) is
      required for neuronal differentiation by mediating the transcriptional activities
      of proneural bHLH proteins.

PMID- 15576412
TI  - Unidirectional Notch signaling depends on continuous cleavage of Delta.
AB  - Unidirectional signaling from cells expressing Delta (Dl) to cells expressing
      Notch is a key feature of many developmental processes. We demonstrate that the
      Drosophila ADAM metalloprotease Kuzbanian-like (Kul) plays a key role in
      promoting this asymmetry. Kul cleaves Dl efficiently both in cell culture and in
      flies, and has previously been shown not to be necessary for Notch processing
      during signaling. In the absence of Kul in the developing wing, the level of Dl
      in cells that normally receive the signal is elevated, and subsequent alterations
      in the directionality of Notch signaling lead to prominent phenotypic defects.
      Proteolytic cleavage of Dl by Kul represents a general mechanism for refining and
      maintaining the asymmetric distribution of Dl, in cases where transcriptional
      repression of Dl expression does not suffice to eliminate Dl protein.

PMID- 15576413
TI  - Development of risk-based guidelines for pediatric cancer survivors: the
      Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's
      Oncology Group Late Effects Committee and Nursing Discipline.
AB  - The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of
      Childhood, Adolescent, and Young Adult Cancers are risk-based, exposure-related
      clinical practice guidelines intended to promote earlier detection of and
      intervention for complications that may potentially arise as a result of
      treatment for pediatric malignancies. Developed through the collaborative efforts
      of the Children's Oncology Group Late Effects Committee, Nursing Discipline, and
      Patient Advocacy Committee, these guidelines represent a statement of consensus
      from a multidisciplinary panel of experts in the late effects of pediatric cancer
      treatment. The guidelines are both evidence-based (utilizing established
      associations between therapeutic exposures and late effects to identify high-risk
      categories) and grounded in the collective clinical experience of experts
      (matching the magnitude of risk with the intensity of screening recommendations).
      They are intended for use beginning 2 or more years following the completion of
      cancer therapy; however, they are not intended to provide guidance for follow-up
      of the survivor's primary disease. A complementary set of patient education
      materials ("Health Links") was developed to enhance follow-up care and broaden
      the application of the guidelines. The information provided in these guidelines
      is important for health care providers in the fields of pediatrics, oncology,
      internal medicine, family practice, and gynecology, as well as subspecialists in
      many fields. Implementation of these guidelines is intended to increase awareness
      of potential late effects and to standardize and enhance follow-up care provided
      to survivors of pediatric cancer throughout the lifespan. The Guidelines, and
      related Health Links, can be downloaded in their entirety at
      www.survivorshipguidelines.org.

PMID- 15576414
TI  - Changes in salivary gland immunohistology and function after rituximab
      monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma.
AB  - OBJECTIVES: To report the successful use of rituximab on salivary gland
      immunohistology and function in a patient with Sjogren's syndrome (SS) and
      associated MALT lymphoma. CASE REPORT: The patient was a 42 year old woman with
      primary SS and associated MALT lymphoma located in the parotid gland and the hard
      palate. Four infusions of rituximab (375 mg/m(2)) weekly resulted in complete
      remission of the lymphoma. An incision biopsy of the parotid gland before and
      after treatment showed improvement of the (immuno)histopathological
      characteristics of SS, with possible regeneration of salivary gland tissue.
      Furthermore, salivary analysis showed decreased inflammatory characteristics and
      increased stimulated salivary flow. DISCUSSION: Rituximab is a promising agent in
      the treatment of SS associated MALT lymphoma. In addition to the effect on MALT
      lymphoma, B cell depletion by rituximab may also attenuate the activity of SS.
      This case report is the first to describe the effect of rituximab on histological
      and sialometric/chemical characteristics of SS. The efficacy of rituximab in the
      treatment of SS warrants further investigation.

PMID- 15576415
TI  - Synovial tissue macrophages: a sensitive biomarker for response to treatment in
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Previous work identified synovial sublining macrophage numbers as a
      potential biomarker for clinical efficacy in rheumatoid arthritis. OBJECTIVE: To
      investigate the association between changes in infiltration of synovial
      macrophages and clinical improvement after antirheumatic treatment. METHODS: 88
      patients who participated in various clinical trials were studied. All patients
      underwent serial arthroscopy before initiation of treatment and after different
      time intervals. Immunohistochemical and digital image analysis were performed
      according to standardised procedures to detect changes in CD68+ synovial
      sublining macrophages in relationship to changes in the 28 joint count Disease
      Activity Score (DAS28). Statistical analysis was performed using one way analysis
      of variance, the independent samples t test, linear regression, and the
      standardised response mean (SRM). RESULTS: For good, moderate, and non
      responders, according to the DAS28 response criteria, there was a significant
      difference in the change in sublining macrophages (mean (SEM) cells/mm(2) -643
      (124), -270 (64), and -95 (60), respectively; p<0.0003). There was a significant
      correlation between the change in the number of macrophages and the change in
      DAS28 (Pearson correlation 0.874, p<0.01). The change in sublining macrophages
      explained 76% of the variation in the change in DAS28 (p<0.02). The sensitivity
      to change of the biomarker was high in patients treated actively (SRM >0.8),
      whereas the ability to detect changes in placebo treated patients was weak (SRM
      <0.3). CONCLUSION: The results suggest that changes in synovial sublining
      macrophages can be used to predict possible efficacy of antirheumatic treatment.

PMID- 15576416
TI  - Raised serum APRIL levels in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether serum levels of a proliferation-inducing ligand
      (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and
      correlate with autoantibody titres or disease activity, or both. METHODS: Serum
      samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients
      with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked
      immunosorbent assay. Medical charts were retrospectively reviewed for
      autoantibody titres and immunoglobulin levels. Disease activity was assessed
      using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: The APRIL
      levels in the serum samples from patients with SLE were significantly higher than
      in those from healthy controls and those from patients with RA. Serum APRIL
      levels did not correlate with serum IgG and IgM levels, but had a tendency to
      correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL
      levels correlated significantly with musculoskeletal manifestations among
      patients with SLE when assessed by the BILAG index. CONCLUSION: APRIL may be an
      important factor in raised autoantibody titres and musculoskeletal disease in
      patients with SLE. Patients with raised serum APRIL levels may be ideal
      candidates for therapeutic targeting of APRIL.

PMID- 15576417
TI  - Impact of musculoskeletal disorders on quality of life: an inception cohort
      study.
AB  - OBJECTIVE: To assess longitudinally the impact of new onset musculoskeletal (MSK)
      disorders on quality of life (QoL). METHODS: An inception cohort of 1202 subjects
      in France aged 45-60 years was determined to be free of MSK problems at baseline.
      Over 28 months of follow up between 1996 and 1998, 310 were diagnosed with MSK
      disorders and matched for age and sex with 620 healthy controls. The impact of
      the MSK disorder onset on QoL was assessed by the change in SF-36 dimension
      scores over time, using a linear mixed ANOVA model to compare the groups.
      RESULTS: The incidence of MSK disorder was 13.6% per person-year in the spine,
      4.2% per person-year in a joint, and 4.6% per person-year at an extra-articular
      site. The greatest change in QoL was a 10 point drop in the 100 point SF-36
      bodily pain dimension scale in the MSK group. Compared with controls, subjects
      with an MSK disorder had significantly greater reductions in the following
      dimensions: bodily pain (a -7.4 point difference in change), vitality (-2.7),
      general health (-1.8), and physical functioning (-1.3). Within the MSK group,
      chronic disorders had a greater impact than acute ones on the physical
      functioning (-2.1), role emotional (-8.4), and social functioning (-5.9)
      dimensions. CONCLUSION: New onset MSK disorders have a marked deleterious effect
      on QoL in the physical domain, with lesser effects on social and mental
      functioning. This evidence of an early significant impact on their QoL reinforces
      recent recommendations for early treatment and primary prevention.

PMID- 15576418
TI  - Human CD14 is an efficient target for recombinant immunoglobulin vaccine
      constructs that deliver T cell epitopes.
AB  - It has been shown in the mouse that recombinant immunoglobulin (Ig) molecules
      with T cell epitopes inserted into the constant domain (Troybodies) can target
      antigen-presenting cells (APC) for efficient delivery of T cell epitopes. Here,
      we have extended the Troybody concept to human applications. Moreover, we show
      that a receptor of innate immunity, CD14, which is a part of the
      lipopolysaccharide receptor complex on monocyte APC, is an efficient target. For
      construction of CD14-specific Troybodies, we used rearranged
      variable(diversity)joining regions cloned from the 3C10 mouse B cell hybridoma.
      As a model T cell epitope, amino acids 40-48 of mouse Ckappa, presented on human
      leukocyte antigen-DR4, were inserted into a loop connecting beta-strands in C(H)1
      of human gamma3. In the presence of monocytes, CD14-specific Troybodies were >100
      times as efficient as a nontargeting control antibody (Ab) at stimulating
      Ckappa(40-48)-specific/DR4-restricted T cells. Presentation was dependent on the
      conventional processing pathway for presentation on major histocompatibility
      complex (MHC) class II molecules. Enhanced presentation of the Ckappa epitope was
      most likely a result of increased loading of MHC class II molecules, as the CD14
      specific monoclonal Ab 3C10 did not induce maturation of the APC. The results
      show that CD14, a receptor of innate immunity, may be a promising target of
      recombinant Ig-based vaccines for elicitation of T cell responses in humans.

PMID- 15576419
TI  - cCXCR1 is a receptor for cIL-8 (9E3/cCAF) and its N- and C-terminal peptides and
      is also activated by hIL-8 (CXCL8).
AB  - Chemokines are chemotactic cytokines that play important roles in immune
      responses and wound healing, as well as in pathological conditions such as
      chronic inflammation and tumorigenesis. The chemokines and their receptors are
      highly conserved and maintain similar functions in different species. One
      noteworthy exception is the chemokine interleukin (IL)8/CXC ligand 8 and its
      specific receptor CXCR1, which are found in humans but are not found in the
      traditional model organisms, mice and rats. As a consequence, we are using model
      organisms other than mice to study the functions of IL-8 and CXCR1, as well as
      the mechanisms involved in receptor activation by IL-8. Toward this goal, we have
      isolated and characterized a new receptor that is highly homologous to human
      (h)CXCR1, which we named chicken (c)CXCR1. To determine whether this receptor is
      activated by cIL-8 and its N- and C-terminal peptides and whether it responds to
      hIL-8, we expressed cCXCR1 in NIH3T3 cells, which naturally lack this receptor,
      and used single-cell Ca(2)(+) imaging to detect increases in intracellular
      Ca(2)(+) and immunoblot analysis to detect extracellular signal-regulated kinase
      1/2 phosphorylation. We show that cIL-8, its N and C peptides, and hIL-8 activate
      cCXCR1. We further show that cIL-8 and hIL-8 stimulate chemotaxis of chicken
      embryonic fibroblasts, cells that express cCXCR1, and that this effect is
      specific for each chemokine and this receptor. These results strongly suggest
      that cCXCR1 is the ortholog for hCXCR1 and that chickens can be used as an
      effective model system to study the functions of IL-8, its terminal peptides, and
      its specific receptor CXCR1.

PMID- 15576420
TI  - The relationship between medicine and the public: the challenge of concordance.
AB  - Concordance is based on the idea that patients and practitioners should work
      together towards an agreement on treatment choice. This requires a redefinition
      of the relations and encounters between doctors and their patients. This
      redefinition emphasizes the need for patient involvement and participation. In
      this article we examine concordance against the background of wider social
      change, structural as well as interpersonal. We focus in particular on challenges
      to trust, noting that the almost instinctive trust that people formerly had for
      professional experts has for many reasons diminished. One consequence of this, we
      suggest, is that concordance is being espoused at a time when its accomplishment
      may be particularly threatened. In fact there are strong grounds for claiming
      that support for the notion of concordance could possibly result in a growth of
      'hidden' communication pathologies by means of what the social theorist Habermas
      (1984) has termed 'systematically distorted communication'.

PMID- 15576421
TI  - The myth of concordance: response to Stevenson and Scambler.

PMID- 15576422
TI  - Rejoinder to 'The myth of concordance': a response to Armstrong.

PMID- 15576423
TI  - Establishing the (extra)ordinary in chronic widespread pain.
AB  - Sufferers of chronic illness face delegitimation of their condition and threats
      to their identities. One way of establishing the legitimacy of their position is
      for sufferers of chronic illness to emphasize the 'ordinary' in their accounts.
      Sufferers of conditions which are chronic, invisible and contested, such as
      chronic widespread pain, have the same, and possibly greater, need to legitimize
      their condition and refute allegations of 'malingering' or psychological
      instability. The article uses interviews with women with chronic widespread pain
      to illustrate the ways in which the invisible, subjective and everyday nature of
      chronic pain leads to sufferers experiencing delegitimation of their condition.
      It suggests that the accounts of women suffering from chronic widespread pain are
      constructed to portray a positive identity in the face of this experience,
      particularly through the emphasis on the 'extraordinary'.

PMID- 15576424
TI  - Fractured identities: injury and the balletic body.
AB  - Social worlds shape human bodies and so it is inevitable that there are strong
      relationships between the body, professional dance and identity. In this article
      we draw on Bourdieu's notions of habitus, and various forms of capital, as the
      main theoretical framework for our discussion. Our ethnography of the balletic
      body elicited dancers and ex-dancers' perceptions of their bodies and sought to
      reveal some of the facets of their embodied habitus. The sheer physicality of
      their working lives - of feeling exhausted, sweaty and out of breath - is
      something dancers (like all athletes) become 'addicted to'. Ageing and injury can
      reveal this compulsion to dance and so dancers invariably find it very difficult
      to, for example, give up class once they retire from the stage; or miss a
      performance if they have a 'slight injury'. In other words, the vocational
      calling to dance is so overwhelming that their balletic body is their identity.
      In addition, there is an unremitting loop between individual habitus and
      institutional habitus (the ballet company), which affects both the meaning and
      management of injury. All our informants at the Royal Ballet (London: n = 20) had
      suffered dance injuries. The injured, dancing body is perceived as an inevitable
      part of a career in ballet. Everyone spoke of the improved athleticism of
      dancers, and of the expansion in facilities to maintain healthy dancers. However,
      most dancers can expect several major injuries during their careers. Such
      epiphanies force dancers to confront their embodiment, and their thoughts
      invariably turn to their body, career and self. Critical injuries threaten to
      terminate a dancer's career and so endanger their embodied sense of self. On a
      more everyday level, dancing and performing with painful, niggling injuries is
      the norm.

PMID- 15576425
TI  - Disruption, dissonance and embodiment: creativity, health and risk in music
      narratives.
AB  - This article explores notions of creativity, health and risk, drawing on
      interviews with freelance musicians in the UK. The social context of insecure
      music work is explored along with hegemonic discourses of creativity in which
      hedonism, risk and sacrifice are connected. The study draws on narrative analysis
      in order to examine responses to disruptions that affect creative work. It also
      explores ongoing accounts of dissonance in music work. The research builds on the
      new musicology in exploring the cultural basis of creative ideals: these extend
      beyond the arts to influence many areas of social life. It highlights the way in
      which the exercise of aesthetic judgements, including judgements about the self,
      serve to include and exclude particular identities, valuing and diminishing their
      contributions. The study also builds on sociological debates concerning the
      regulatory functions of reflexivity and body management in the context of late
      modernity. Here, strategies of embodiment are also seen in relation to
      empowerment as challenges to hegemonic notions of creativity. Finally, the
      research builds on methodological debates surrounding narrative analysis,
      adopting a sociological approach that emphasizes the particular context of music
      work and identifies core narratives that reveal connections between everyday
      experiences and deeper cultural processes.

PMID- 15576426
TI  - Politicizing dominant discursive constructions about teenage pregnancy: re
      locating the subject as social.
AB  - Authors of research examining the issue of teenage pregnancy represent
      authoritative social voices, in strong positions of warrant that participate in
      shaping dominant social attitudes towards the subject. Their research projects
      are used to develop policies, information, service provision and practices that
      are major forces in shaping the actual experience of being pregnant as a
      teenager. This article examines local examples of such research and locates
      interpretation of these alongside other international studies. Prevalent in the
      research is the taken for granted assumption that pregnancy in adolescence is
      undesirable, and that research knowledge can, and should be, applied to reduce
      rates of teenage pregnancy. Despite clear indications of social issues being a
      major source of negative impacts of being pregnant in adolescence, the dominant
      theme is of teenage pregnancy as an individual health or behavioural problem in
      need of a psychological solution. This article would like to draw attention to
      and make visible the contingent, political and potentially problematic nature of
      those constructions. The suggestion is made that future work could benefit from
      genuine attention to: 1) social issues, especially in relation to resources and
      access; 2) work that explores meanings around pregnancy for young people, and 3)
      the application of politically engaged reflexivity in research.

PMID- 15576427
TI  - Effect of blood collection tubes on total triiodothyronine and other laboratory
      assays.
AB  - BACKGROUND: Increased total triiodothyronine (TT(3)) assay results in apparently
      euthyroid patients triggered an investigation of the effect of blood collection
      tubes on serum TT(3) and other laboratory assays. METHODS: We examined potential
      assay interference for three types of tubes: plastic Greiner Bio-One Vacuette;
      glass Becton Dickinson (BD) Vacutainer; and plastic BD Vacutainer SST tubes.
      Serum samples from apparently healthy volunteers (age range, 30-60 years; 15
      males and 34 females) were collected in different tube types and analyzed in 17
      immunoassays (n = 49), 30 clinical chemistry tests (n = 20), and 33 immunology
      assays (n = 15). Tube effects were also examined by adding pooled serum to
      different tube types. RESULTS: TT(3) values, when measured by the IMMULITE 2000
      but not the AxSYM analyzer, were significantly higher (P <0.0001) for SST (2.81
      nmol/L) than either glass (2.15 nmol/L) or Vacuette (2.24 nmol/L) tubes. The
      effect was large enough to substantially shift the distribution of patient
      values, increasing the percentage of values above the reference interval from
      11.3% to 35.8%. The degree of interference from SST tubes on TT(3) differed among
      various tube lots and could be attributed to a tube additive shared by other
      plastic tubes. Results from several other tests statistically differed among tube
      types, but differences were not considered to be clinically significant.
      CONCLUSIONS: Assay interferences from blood collection tubes represent challenges
      to clinical laboratories because they are not detected by the usual quality
      control or proficiency testing programs. Laboratories can, however, address this
      problem by monitoring distribution of patients' results.

PMID- 15576428
TI  - Urinary excretion of homocysteine-thiolactone in humans.
AB  - BACKGROUND: A metabolite of homocysteine (Hcy), the thioester Hcy-thiolactone,
      has been implicated in coronary heart disease in humans. Because inadvertent
      reactions of Hcy-thiolactone with proteins can lead to cell and tissue damage,
      the ability to detoxify or eliminate Hcy-thiolactone is essential for biological
      integrity. We examined the hypothesis that the human body eliminates Hcy
      thiolactone by urinary excretion. METHODS: We used a sensitive HPLC method with
      postcolumn derivatization and fluorescence detection to examine Hcy-thiolactone
      concentrations in human urine and plasma. RESULTS: We discovered a previously
      unknown pool of Hcy-thiolactone in human urine. Urinary concentrations of Hcy
      thiolactone (11-485 nmol/L; n = 19) were approximately 100-fold higher than those
      in plasma (<0.1-22.6 nmol/L; n = 20). Urinary Hcy-thiolactone accounted for 2.5
      28.3% of urinary total Hcy, whereas plasma Hcy-thiolactone accounted for <0.002
      0.29% of plasma total Hcy. Urinary concentrations of Hcy-thiolactone, but not of
      total Hcy, were negatively correlated with urinary pH. Clearance of Hcy
      thiolactone, relative to creatinine, was 0.21-6.96. In contrast, relative
      clearance of Hcy was 0.001-0.003. CONCLUSIONS: The analytical methods described
      here can be used to quantify Hcy-thiolactone in biological fluids. Using these
      methods we showed that the human body eliminates Hcy-thiolactone by urinary
      excretion. Our data also suggest that the protonation status of its amino group
      affects Hcy-thiolactone excretion.

PMID- 15576429
TI  - Apolipoprotein C-III, n-3 polyunsaturated fatty acids, and "insulin-resistant" T
      455C APOC3 gene polymorphism in heart disease patients: example of gene-diet
      interaction.
AB  - BACKGROUND: Apolipoprotein C-III (apo C-III) is a marker of cardiovascular
      disease risk associated with triglyceride (TG)-rich lipoproteins. The T-455C
      polymorphism in the insulin-responsive element of the APOC3 gene influences TG
      and apo C-III concentrations. Long-chain n-3 polyunsaturated fatty acids (PUFAs)
      contained in fish have well-known apo C-III-lowering properties. METHODS: We
      investigated the possibility of an interactive effect between the APOC3 gene
      variant and erythrocyte n-3 PUFAs, suitable markers of dietary intake of fatty
      acids, on apo C-III concentrations in a population of 848 heart disease patients
      who had coronary angiography. RESULTS: In the population as a whole, apo C-III
      concentrations were significantly inversely correlated with total erythrocyte
      PUFAs, but the correlation was not significant when only -455CC homozygous
      individuals were taken into account. In the total population and in subgroups
      with the -455TT and -455CT genotypes, the relative proportions of individuals
      presenting with increased apo C-III (i.e., above the 75th percentile value
      calculated on the entire population after exclusion of individuals taking lipids
      lowering medications) decreased progressively as the n-3 PUFA and docosahexaenoic
      acid concentrations increased. The opposite situation was observed in the
      homozygous -455CC subgroup, in whom increasing erythrocyte n-3 PUFA and
      docosahexaenoic acid concentrations were associated with higher proportions of
      individuals with high apo C-III. A formal interactive effect between genotype and
      n-3 PUFAs was confirmed even after adjustment for possible confounding variables
      [age, sex, body mass index, smoking, coronary artery disease (CAD)/CAD-free
      status, or use of lipid-lowering medications] by logistic models. CONCLUSION:
      Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo
      C-III-lowering effects of n-3 PUFAs.

PMID- 15576430
TI  - N-methyl-D-aspartate receptor activation in human cerebral endothelium promotes
      intracellular oxidant stress.
AB  - Cerebral endothelial cells in the rat, pig, and, most recently, human have been
      shown to express several types of receptors specific for glutamate. High levels
      of glutamate disrupt the cerebral endothelial barrier via activation of N-methyl
      d-aspartate (NMDA) receptors. We have previously suggested that this glutamate
      induced barrier dysfunction was oxidant dependent. Here, we provide evidence that
      human cerebral endothelial cells respond to glutamate by generating an
      intracellular oxidant stress via NMDA receptor activation. Cerebral endothelial
      cells loaded with the oxidant-sensitive probe dihydrorhodamine were used to
      measure intracellular reactive oxygen species (ROS) formation in response to
      glutamate receptor agonists, antagonists, and second message blockers. Glutamate
      (1 mM) significantly increased ROS formation compared with sham controls (30
      min). This ROS response was significantly reduced by 1) MK-801, a noncompetitive
      NMDA receptor antagonist; 2) 8-(N,N-diethylamino)-n-octyl-3,4,5
      trimethoxybenzoate, an intracellular Ca(2+) antagonist; 3) LaCl(3), an
      extracellular Ca(2+) channel blocker; 4) diphenyleiodonium, a heme-ferryl
      containing protein inhibitor; 5) itraconazole, a cytochrome P-450 3A4 inhibitor;
      and 6) cyclosporine A, which prevents mitochondrial membrane pore transition
      required for mitochondrial-dependent ROS generation. Our results suggest that the
      cerebral endothelial barrier dysfunction seen in response to glutamate is Ca(2+)
      dependent and may require several intracellular signaling events mediated by
      oxidants derived from reduced nicotinamide adenine dinucleotide oxidase,
      cytochrome P-450, and the mitochondria.

PMID- 15576431
TI  - Essential role of protein kinase G and decreased cytoplasmic Ca2+ levels in NO
      induced inhibition of rat aortic smooth muscle cell motility.
AB  - Hyperinsulinemia is a major risk factor for the development of vascular disease.
      We have reported that insulin increases the motility of vascular smooth muscle
      cells via a hydrogen peroxide-mediated mechanism and that nitric oxide (NO)
      attenuates insulin-induced motility via a cGMP-mediated mechanism. Events
      downstream of cGMP elevation have not yet been investigated. The aim of our study
      was to test the hypothesis that antimotogenic effects of NO and cGMP in cultured
      rat aortic smooth muscle cells are mediated via PKG, followed by reduction of
      cytoplasmic Ca(2+) levels and increased protein tyrosine phosphatase-proline,
      glutamate, serine, and threonine activity, leading to suppression of agonist
      induced elevation of hydrogen peroxide levels and cell motility. Treatment of
      primary cultures with adenovirus expressing PKG-1alpha mimicked NO-induced
      inhibition of insulin-elicited hydrogen peroxide elevation and cell motility,
      whereas treatment with the pharmacological PKG inhibitor Rp-8-bromo-3',5'-cyclic
      monophosphorothioate (Rp-8-Br-cGMPS) rescued the stimulatory effects of insulin
      that were suppressed by NO donor. Treatment of cells with insulin failed to
      increase cytoplasmic Ca(2+) levels, whereas NO donor decreased cytoplasmic Ca(2+)
      levels in the presence or absence of insulin. Treatment of cells with the Ca(2+)
      chelator BAPTA mimicked the effects of PKG and the NO donor and increased the
      activity of PTP-PEST. Finally, treatment with a dominant negative allele of PTP
      PEST reversed the inhibitory effect of BAPTA on cell motility and hydrogen
      peroxide elevation. We conclude that NO-induced inhibition of cell motility
      occurs via PKG-mediated reduction of basal cytoplasmic Ca(2+) levels, followed by
      increased PTP-PEST activity, leading to decreased hydrogen peroxide levels and
      reduced cell motility.

PMID- 15576432
TI  - Elevated plasma viscosity in extreme hemodilution increases perivascular nitric
      oxide concentration and microvascular perfusion.
AB  - We tested the hypothesis that high-viscosity (HV) plasma in extreme hemodilution
      causes wall shear stress to be greater than low-viscosity (LV) plasma, leading to
      enhanced production of nitric oxide (NO). The perivascular concentration of NO
      was measured in arterioles and venules and the tissue of the hamster chamber
      window model, subjected to acute extreme hemodilution, with a hematocrit (Hct) of
      11% using Dextran 500 (n = 6) or Dextran 70 (n = 5) with final plasma viscosities
      of 1.99 +/- 0.11 and 1.33 +/- 0.04 cp, respectively. HV plasma significantly
      increased the periarteriolar, perivenular, and tissue NO concentration by 2.0,
      1.9, and 1.4 times the control (n = 7). The NO concentration with LV plasma was
      not statistically different from control. Arteriolar shear stress was
      significantly increased in HV plasma relative to LV plasma in arterioles but not
      in venules. Aortic endothelial NO synthase (eNOS) protein expression was
      increased with HV plasma but not with LV plasma. There was a weak correlation
      between perivascular NO concentration and the locally calculated shear stress
      induced by the procedures, when blood viscosity was corrected according to Hct
      values previously determined in studies of microvascular Hct distribution. The
      finding that the periarteriolar and venular NO concentration in HV plasma was the
      same although arteriolar shear stress was significantly greater than venular
      shear stress maybe be due to differences in vessel wall metabolism between
      arterioles and venules and the presence of NO transport through the blood stream
      in the microcirculation. Results support the concept that in extreme hemodilution
      HV plasma maintains functional capillary density through a NO-mediated
      vasodilatation.

PMID- 15576433
TI  - Resistance artery vasodilation to magnesium sulfate during pregnancy and the
      postpartum state.
AB  - This study compared the vasodilatory responses to magnesium sulfate (MgSO(4)) of
      cerebral and mesenteric resistance arteries and determined whether the responses
      varied between different gestational groups. Third-order branches (<200 microm)
      of the posterior cerebral (PCA) and mesenteric arteries (MA) were dissected from
      nonpregnant (NP; n = 6), late pregnant (LP; day 19, n = 6), and postpartum (PP;
      day 3, n = 6) Sprague-Dawley rats. A concentration-response curve was performed
      by replacing the low-MgSO(4) (1.2 mM) HEPES buffer solution with increasing
      concentrations of MgSO(4) (4, 6, 8, 16, and 32 mM) and measuring lumen diameter
      at each concentration. All groups exhibited concentration-dependent dilation to
      MgSO(4), decreasing the amount of tone in the vessels. However, MA were
      significantly more sensitive to MgSO(4) than PCA. Whereas there was no difference
      in the response between different gestational groups in MA, the PCA from the LP
      and PP groups showed a significantly diminished response to MgSO(4). The percent
      dilation at 32 mM MgSO(4) for PCA versus MA in NP, LP, and PP animals was 36 +/-
      2 vs. 51 +/- 7% (P < 0.05), 19 +/- 9 vs. 54 +/- 6% (P < 0.01 vs. PCA and NP), and
      12 +/- 5 vs. 52 +/- 11% (P < 0.01 vs. PCA and NP). These results demonstrate that
      MgSO(4) is a vasodilator of small resistance arteries in the cerebral and
      mesenteric vascular beds. The refractory responses of the PCA in LP and PP groups
      demonstrate changes in the cerebrovascular vasodilatory mechanisms with
      gestation. The greater sensitivity of the MA to MgSO(4)-induced vasodilation
      suggests that the prophylactic effect of MgSO(4) on eclamptic seizures may be
      more closely related to the lowering of systemic blood pressure than to an effect
      on cerebral blood flow.

PMID- 15576434
TI  - Regional myocardial perfusion under exchange transfusion with liposomal
      hemoglobin: in vivo and in vitro studies using rat hearts.
AB  - The purpose of this study was to test the hypothesis that exchange transfusion
      with liposomal hemoglobin (LH) reduces the microheterogeneity of regional
      myocardial flows while sustaining cardiac function. Neo Red Cell mixed with
      albumin was used as the LH solution, in which the LH volume fraction was 17
      approximately 18% and hemoglobin density was nearly two-thirds smaller than in
      rat blood. Regional myocardial flows in left ventricular free walls were measured
      by tracer digitalradiography (100-mum resolution) in anesthetized rats with or
      without 50% blood-LH exchange transfusion. Within-layer flow distributions showed
      lower heterogeneity with (n = 8) than without (n = 8) LH transfusion. No
      extravasation of hemoglobin was confirmed by 3,3-diaminobenzidin staining (n =
      2). Carotid flow increased by 68% due to LH transfusion, whereas arterial
      pressure and heart rate remained unchanged. On the other hand, cross-circulated
      rat hearts (n = 7) were used to evaluate the effects of 50% blood-LH exchange on
      coronary flow and tone preservation under 300-beats/min pacing and 100-mmHg
      perfusion pressure. Blood-LH exchange caused a 71% increase of coronary flow and
      10% decrease of percent flow increase during hyperemia after 30-s flow
      interruption. Myocardial O(2) supply and consumption increased by 9% and 10%,
      respectively, whereas myocardial O(2) extraction remained unchanged. The large
      increases of in vivo carotid flow and coronary flow in cross-circulated hearts
      due to LH coperfusion could be explained by the reduction of apparent flow
      viscosity. These results suggest that under LH coperfusion, the
      microheterogeneity of myocardial flows decreases with increased coronary flow
      while fairly preserving coronary tone and cardiac function.

PMID- 15576435
TI  - Vascular adaptation to 4 wk of deconditioning by unilateral lower limb
      suspension.
AB  - Physical inactivity or deconditioning is an independent risk factor for
      atherosclerosis and cardiovascular disease. In contrast to exercise, the vascular
      changes that occur as a result of deconditioning have not been characterized. We
      used 4 wk of unilateral lower limb suspension (ULLS) to study arterial and venous
      adaptations to deconditioning. In contrast to previous studies, this model is not
      confounded by denervation or microgravity. Seven healthy subjects participated in
      the study. Arterial and venous characteristics of the legs were assessed by echo
      Doppler ultrasound and venous occlusion plethysmography. The diameter of the
      common and superficial femoral artery decreased by 12% after 4 wk of ULLS.
      Baseline calf blood flow, as measured by plethysmography, decreased from 2.1 +/-
      0.2 to 1.6 +/- 0.2 ml.min(-1).dl tissue(-1). Both arterial diameter and calf
      blood flow returned to baseline values after 4 wk of recovery. There was no
      indication of a decrease in flow-mediated dilation of the superficial femoral
      artery after ULLS deconditioning. This means that functional adaptations to
      inactivity are not simply the inverse of adaptations to exercise. The venous
      pressure-volume curve is shifted downward after ULLS, without any effect on
      compliance. In conclusion, deconditioning by 4 wk of ULLS causes significant
      changes in both the arterial and the venous system.

PMID- 15576436
TI  - Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells
      into vascular endothelial cells in vitro.
AB  - Pluripotent embryonic stem (ES) cells are capable of differentiating into all
      cell lineages, but the molecular mechanisms that regulate ES cell differentiation
      have not been sufficiently explored. In this study, we report that shear stress,
      a mechanical force generated by fluid flow, can induce ES cell differentiation.
      When Flk-1-positive (Flk-1(+)) mouse ES cells were subjected to shear stress,
      their cell density increased markedly, and a larger percentage of the cells were
      in the S and G(2)-M phases of the cell cycle than Flk-1(+) ES cells cultured
      under static conditions. Shear stress significantly increased the expression of
      the vascular endothelial cell-specific markers Flk-1, Flt-1, vascular endothelial
      cadherin, and PECAM-1 at both the protein level and the mRNA level, but it had no
      effect on expression of the mural cell marker smooth muscle alpha-actin, blood
      cell marker CD3, or the epithelial cell marker keratin. These findings indicate
      that shear stress selectively promotes the differentiation of Flk-1(+) ES cells
      into the endothelial cell lineage. The shear stressed Flk-1(+) ES cells formed
      tubelike structures in collagen gel and developed an extensive tubular network
      significantly faster than the static controls. Shear stress induced tyrosine
      phosphorylation of Flk-1 in Flk-1(+) ES cells that was blocked by a Flk-1 kinase
      inhibitor, SU1498, but not by a neutralizing antibody against VEGF. SU1498 also
      abolished the shear stress-induced proliferation and differentiation of Flk-1(+)
      ES cells, indicating that a ligand-independent activation of Flk-1 plays an
      important role in the shear stress-mediated proliferation and differentiation by
      Flk-1(+) ES cells.

PMID- 15576437
TI  - Sarcoplasmic reticulum Ca2+ transport and gene expression in congestive heart
      failure are modified by imidapril treatment.
AB  - This study was designed to test the hypothesis that blockade of the renin
      angiotensin system improves cardiac function in congestive heart failure by
      preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We
      employed rats with myocardial infarction (MI) to examine effects of an
      angiotensin-converting enzyme inhibitor, imidapril, on SR Ca(2+) transport,
      protein content, and gene expression. Imidapril (1 mg.kg(-1).day(-1)) was given
      for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited
      a fourfold increase in left ventricular end-diastolic pressure, whereas rates of
      pressure development and decay were decreased by 60 and 55%, respectively. SR
      Ca(2+) uptake and Ca(2+) pump ATPase, as well as Ca(2+) release and ryanodine
      receptor binding activities, were depressed in the failing hearts; protein
      content and mRNA levels for Ca(2+) pump ATPase, phospholamban, and ryanodine
      receptor were also decreased by approximately 55-65%. Imidapril treatment of
      infarcted animals improved cardiac performance and attenuated alterations in SR
      Ca(2+) pump and Ca(2+) release activities. Changes in protein content and mRNA
      levels for SR Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also
      prevented by imidapril treatment. Beneficial effects of imidapril on cardiac
      function and SR Ca(2+) transport were not only seen at different intervals of MI
      but were also simulated by another angiotensin-converting enzyme inhibitor,
      enalapril, and an ANG II receptor antagonist, losartan. These results suggest
      that blockade of the renin-angiotensin system may increase the abundance of mRNA
      for SR proteins and, thus, may prevent the depression in SR Ca(2+) transport and
      improve cardiac function in congestive heart failure due to MI.

PMID- 15576438
TI  - Effects of tetraiodothyronine and triiodothyronine on hamster cheek pouch
      microcirculation.
AB  - The aim of the present study was to assess the effects of topically applied
      triiodothyronine (T(3)) and thyroxine (T(4)) on the arterioles of hamster cheek
      pouch microcirculation in vivo. Microvessels were visualized using a fluorescent
      microscopy technique. Topical application of T(3) (3.08, 30.8, 61.5, 307, 615,
      and 6,150 nM/l) consistently induced dose-dependent dilation of arterioles within
      2.0 +/- 0.5 min of administration. The application of T(4) (150, 257, 514, and
      5,140 nM/l) caused different dose-dependent effects: dilation at the three lower
      doses within 16 +/- 2 min and rhythmic diameter changes at the highest dose.
      Aging of hamsters did not alter the arteriolar responses to T(3) and T(4). T(3)
      induced dilation was countered by the inhibition of nitric oxide synthase with
      N(G)-nitro-L-arginine-methyl ester or N(G)-nitro-L-arginine. Iopanoic acid (IPA),
      which inhibits types I and II 5'-deiodinase, abolished the dilation elicited by
      514 nM T(4) but did not affect T(3)-dependent dilation. 6-Propyl-2-thiouracil
      (PTU), which inhibits type I 5'-deiodinase only, did not affect the dilation
      induced by T(4). IPA and PTU did not impair arteriolar dilation induced by
      acetylcholine or sodium nitroprusside. These results indicate that T(3) induces
      arteriolar dilation, likely through nitric oxide release. The local conversion of
      T(4) to T(3) appears to be crucial for the dilation induced by T(4).

PMID- 15576439
TI  - Simulated microgravity enhances cerebral artery vasoconstriction and vascular
      resistance through endothelial nitric oxide mechanism.
AB  - Elevations in arterial pressure associated with hypertension, microgravity, and
      prolonged bed rest alter cerebrovascular autoregulation in humans. Using head
      down tail suspension (HDT) in rats to induce cephalic fluid shifts and elevate
      arterial pressure, this study tested the hypothesis that 2-wk HDT enhances
      cerebral artery vasoconstriction and that an enhanced vasoconstriction described
      in vitro will alter regional cerebral blood flow (CBF) and vascular resistance
      (CVR) during standing and head-up tilt. To test this hypothesis, basal tone and
      vasoconstrictor responses to increases in transmural pressure, shear stress, and
      K(+) were determined in vitro in middle cerebral arteries (MCAs) from HDT and
      control rats. All in vitro measurements were done in the presence and absence of
      the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L
      NAME; 10(-5) M) and with endothelium removal. Endothelial NOS (eNOS) mRNA and
      protein expression levels were measured by RT-PCR and immunoblot, respectively.
      Regional CBF and CVR were determined with a radiolabeled tracer technique and
      quantitative autoradiography. Basal tone and all vasoconstrictor responses were
      greater in MCAs from HDT rats. L-NAME and endothelium removal abolished these
      differences between groups, and HDT was associated with lower levels of MCA eNOS
      protein. CBF in select regions was lower and CVR higher during standing and head
      up tilt in HDT rats. These results indicate that chronic cephalic fluid shifts
      enhanced basal tone and vasoconstriction through alterations in the eNOS
      signaling mechanism. The functional consequence of these vascular alterations
      with HDT is regional elevations in CVR and corresponding reductions in cerebral
      perfusion.

PMID- 15576440
TI  - Effects of BDM, [Ca2+]o, and temperature on the dynamic stiffness of quiescent
      cardiac trabeculae from rat.
AB  - Studies of the passive mechanical properties of cardiac tissue have traditionally
      been conducted at subphysiological temperatures and various concentrations of
      extracellular Ca(2+) ([Ca(2+)](o)). More recently, the negative inotropic agent
      2,3-butanedione monoxime (BDM) has been used. However, there remains a lack of
      data regarding the influence of temperature, Ca(2+), and BDM on the passive
      mechanical properties of cardiac tissue. We have used the dynamic stiffness
      technique, a sensitive measurement of cross-bridge activity, in which minute
      (approximately 0.2% of muscle length) sinusoidal perturbations are applied at
      various frequencies (0.2-100 Hz) to quiescent, viable right ventricular rat
      trabeculae at two temperatures (20 degrees C and 26 degrees C) and at two
      [Ca(2+)](o) (0.5 and 1.25 mM) in the presence and absence of BDM (20 mM). The
      stiffness spectra (amplitude and phase) were sensitive to temperature and
      [Ca(2+)](o) in the absence of BDM but insensitive in the presence of BDM. From
      the index of cross-bridge cycling (the ratio of high- to low-frequency stiffness
      amplitude), we infer that BDM inhibits a small degree of spontaneous sarcomere
      activity, thereby allowing the true passive properties of trabeculae to be
      determined. In the absence of BDM, the extent of spontaneous sarcomere activity
      decreases with increasing temperature. We caution that the measured mechanical
      properties of passive cardiac tissue are critically dependent on the experimental
      conditions under which they are measured. Experiments must be performed at
      sufficiently high temperatures (>25 degrees C) to ensure a low resting
      concentration of intracellular Ca(2+) or in the presence of an inhibitor of cross
      bridge cycling.

PMID- 15576441
TI  - Sympathetic, sensory, and nonneuronal contributions to the cutaneous
      vasoconstrictor response to local cooling.
AB  - Previous work indicates that sympathetic nerves participate in the vascular
      responses to direct cooling of the skin in humans. We evaluated this hypothesis
      further in a four-part series by measuring changes in cutaneous vascular
      conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30
      min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/-
      6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did
      not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9%
      bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and
      propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2%
      control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on
      the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P
      > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no
      significant effect on either phase of vasoconstriction (P > 0.05 between sites
      both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also
      reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of
      vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ
      significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P >
      0.05 between treatments). These results indicate that local cooling causes cold
      sensitive afferents to activate sympathetic nerves to release norepinephrine,
      leading to a local cutaneous vasoconstriction that masks a nonneurogenic
      vasodilation. Later, a vasoconstriction develops with or without functional
      sensory or sympathetic nerves.

PMID- 15576442
TI  - Effects of high-salt diet on CYP450-4A omega-hydroxylase expression and active
      tone in mesenteric resistance arteries.
AB  - This study investigated the role of changes in the expression of the cytochrome P
      450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE)
      in modulating the responses of rat mesenteric resistance arteries to
      norepinephrine (NE) and reduced Po(2) after short-term (3-day) changes in dietary
      salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR
      in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only
      the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4%
      NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly
      increased by a HS diet. Inhibiting 20-HETE synthesis with 30 muM N-methylsulfonyl
      12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE
      in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity
      after DDMS treatment was significantly lower in vessels from rats on a HS diet.
      DDMS treatment also restored the vasodilator response to reduced Po(2) that was
      impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS
      diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature,
      2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric
      resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor
      response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and
      4) upregulation of the production of 20-HETE contributes to the impaired dilation
      of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.

PMID- 15576443
TI  - Evidence for a functional calcium-sensing receptor that modulates myogenic tone
      in rat subcutaneous small arteries.
AB  - Myogenic tone of small arteries is dependent on the presence of extracellular
      calcium (Ca(o)(2+)), and, recently, a receptor that senses changes in Ca(2+), the
      calcium-sensing receptor (CaR), has been detected in vascular tissue. We
      investigated whether the CaR is involved in the regulation of myogenic tone in
      rat subcutaneous small arteries. Immunoblot analysis using a monoclonal antibody
      against the CaR demonstrated its presence in rat subcutaneous arteries. To
      determine whether the CaR was functionally active, segments of artery (< 250
      microm internal diameter) mounted in a pressure myograph with an intraluminal
      pressure of 70 mmHg were studied after the development of myogenic tone.
      Increasing Ca(o)(2+) concentration ([Ca(2+)](o)) cumulatively from 0.5 to 10 mM
      induced an initial constriction (0.5-2 mM) followed by dilation (42 +/- 5% loss
      of tone). The dose-dependent dilation was mimicked by other known CaR agonists
      including magnesium (1-10 mM) and the aminoglycosides neomycin (0.003-10 mM) and
      kanamycin (0.003-3 mM). PKC activation with the phorbol ester phorbol-12,13
      dibutyrate (20nM) inhibited the dilation induced by high [Ca(2+)](o) or neomycin,
      whereas inhibition of PKC with GF109203X (10 microM) increased the responses to
      Ca(o)(2+) or neomycin, consistent with the role of PKC as a negative regulator of
      the CaR. We conclude that rat subcutaneous arteries express a functionally active
      CaR that may be involved in the modulation of myogenic tone and hence the
      regulation of peripheral vascular resistance.

PMID- 15576444
TI  - Muscle metaboreflex modulates the arterial baroreflex dynamic effects on
      peripheral vascular conductance in humans.
AB  - We aimed to investigate the interaction between the arterial baroreflex and
      muscle metaboreflex [as reflected by alterations in the dynamic responses shown
      by leg blood flow (LBF: by the ultrasound Doppler method), leg vascular
      conductance (LVC), mean arterial blood pressure (MAP), and heart rate (HR)] in
      humans. In 12 healthy subjects (10 men and 2 women), who performed sustained 1
      min handgrip exercise at 50% maximal voluntary contraction followed immediately
      by an imposed postexercise muscle ischemia (PEMI), 5-s periods of neck pressure
      (NP; 50 mmHg) or neck suction (NS; -60 mmHg) were used to evaluate carotid
      baroreflex function both at rest (Con) and during PEMI. First, the decreases in
      LVC and LBF and the augmentation of MAP elicited by NP were all greater during
      PEMI than in Con (DeltaLVC, -1.2 +/- 0.2 vs. -1.9 +/- 0.2 ml.min(-1).mmHg(-1);
      DeltaLBF, -97.3 +/- 11.2 vs. -177.0 +/- 21.8 ml/min; DeltaMAP, 6.7 +/- 1.2 vs.
      11.5 +/- 1.4 mmHg, Con vs. PEMI; each P < 0.05). Second, in Con, NS significantly
      increased both LVC and LBF (DeltaLVC, 0.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF,
      46.6 +/- 9.8 ml/min; significant change from baseline: each P < 0.05), and,
      whereas during PEMI no significant increases in LVC and LBF occurred during NS
      itself (DeltaLVC, 0.2 +/- 0.1 ml.min(-1).mmHg(-1); DeltaLBF, 10.8 +/- 9.6 ml/min;
      each P > 0.05), a decrease was evident in each parameters at 5 s after the
      cessation of NS. Third, during PEMI, the decrease in MAP elicited by NS was
      smaller (DeltaMAP, -8.4 +/- 1.0 vs. -5.8 +/- 0.4 mmHg, Con vs. PEMI; P < 0.05),
      and it recovered to its initial level more quickly after NS (vs. Con). Finally,
      however, the HR responses to NS and NP were not different between PEMI and Con.
      These results suggest that during muscle metaboreflex activation in humans, the
      arterial baroreflex dynamic effect on peripheral vascular conductance is
      modulated, as exemplified by 1) an augmentation of the NP-induced LVC decrease,
      and 2) a loss of the NS-induced LVC increase.

PMID- 15576445
TI  - Increased expression and altered subcellular distribution of PKC-delta in
      chronically hypoxic rat myocardium: involvement in cardioprotection.
AB  - We examined the role of protein kinase C (PKC) in the cardioprotective mechanism
      induced by long-term adaptation to chronic intermittent hypoxia. Adult male
      Wistar rats were exposed to hypobaric hypoxia of 7,000 m for 8 h/day, 5 days/wk;
      the total number of exposures was 24-32. A control group was kept under normoxic
      conditions. Western blot analysis of PKC isoforms-delta and -epsilon was
      performed in the cytosol and three particulate fractions of left ventricular
      myocardium. Infarct size was determined in open-chest animals subjected to 20-min
      coronary artery occlusion and 3-h reperfusion. The PKC inhibitors chelerythrine
      (1 or 5 mg/kg) or rottlerin (selective for PKC-delta isoform; 0.3 mg/kg) were
      administered intravenously as a single bolus 15 min before ischemia. Chronic
      hypoxia had no effect on the expression and distribution of PKC-epsilon. The
      relative amount of PKC-delta increased in the cytosol and nuclear-cytoskeletal,
      mitochondrial, and microsomal fractions of chronically hypoxic myocardium by
      100%, 212%, 237%, and 146%, respectively, compared with corresponding normoxic
      values. Chronic hypoxia decreased the size of myocardial infarction (normalized
      to the area at risk) by about one-third on the average (P < 0.05). Both doses of
      chelerythrine tended to reduce infarction in controls, and only the high dose
      completely abolished the improvement of ischemic tolerance in hypoxic hearts (P <
      0.05). Rottlerin attenuated the infarct size-limiting effect of chronic hypoxia
      (P < 0.05), and it had no effect in controls. These results suggest that chronic
      intermittent hypoxia-induced cardioprotection in rats is partially mediated by
      PKC-delta; the contribution of other isoforms remains to be determined.

PMID- 15576446
TI  - Time course of flow-induced vasodilation in skeletal muscle: contributions of
      dilator and constrictor mechanisms.
AB  - The purpose of this study was to determine the time course of flow-induced
      vasodilation in soleus and gastrocnemius muscle arterioles and the mechanisms
      that underlie vasodilatory responses to an increase in intraluminal flow.
      Vasodilation was assessed during 20 min of continuous exposure to intraluminal
      flow. Both soleus and gastrocnemius muscle arterioles dilated in response to
      flow, although the magnitude of vasodilation was greater in arterioles from the
      gastrocnemius muscle. Neither blockade of nitric oxide synthase with N(G)-nitro-L
      arginine methyl ester (L-NAME) nor blockade of cyclooxygenase with indomethacin
      inhibited the initial vasodilation (0-2 min) in arterioles from either muscle. In
      contrast, vasodilation to sustained exposure to flow (2-20 min) was eliminated by
      treatment with L-NAME in arterioles from both muscles. Both depolarization with
      40 mM KCl and blockade of Ca(2+)-activated K(+) channels inhibited the initial
      flow-induced dilation, and the inhibition was greater in gastrocnemius muscle
      arterioles than soleus muscle arterioles. In the presence of L-NAME, prolonged
      exposure to flow resulted in constriction in soleus and gastrocnemius muscle
      arterioles. This constriction was abolished by endothelin receptor blockade.
      These results indicate that the time course and magnitude of flow-induced
      vasodilation differs between arterioles from soleus and gastrocnemius muscles.
      The immediate response to increased flow is greater in gastrocnemius muscle
      arterioles and involves activation of K(+) channels. In arterioles from both
      soleus and gastrocnemius muscles, vasodilation to sustained flow exposure occurs
      primarily through production of nitric oxide. In the absence of nitric oxide,
      sustained exposure to flow results in pronounced constriction that is mediated by
      endothelin.

PMID- 15576447
TI  - The cyp2e1-humanized transgenic mouse: role of cyp2e1 in acetaminophen
      hepatotoxicity.
AB  - The cytochrome P450 (P450) CYP2E1 enzyme metabolizes and activates a wide array
      of toxicological substrates, including alcohols, the widely used analgesic
      acetaminophen, acetone, benzene, halothane, and carcinogens such as azoxymethane
      and dimethylhydrazine. Most studies on the biochemical and pharmacological
      actions of CYP2E1 are derived from studies with rodents, rabbits, and cultured
      hepatocytes; therefore, extrapolation of the results to humans can be difficult.
      Creating "humanized" mice by introducing the human CYP2E1 gene into Cyp2e1-null
      mice can circumvent this disadvantage. A transgenic mouse line expressing the
      human CYP2E1 gene was established. Western blot and high-performance liquid
      chromatography/mass spectrometry analyses revealed human CYP2E1 protein
      expression and enzymatic activity in the liver of CYP2E1-humanized mice.
      Treatment of mice with the CYP2E1 inducer acetone demonstrated that human CYP2E1
      was inducible in this transgenic model. The response to the CYP2E1 substrate
      acetaminophen was explored in the CYP2E1-humanized mice. Hepatotoxicity,
      resulting from the CYP2E1-mediated activation of acetaminophen, was demonstrated
      in the livers of CYP2E1-humanized mice by elevated serum alanine aminotransferase
      levels, increased hepatocyte necrosis, and decreased P450 levels. These data
      establish that in this humanized mouse model, human CYP2E1 is functional and can
      metabolize and activate different CYP2E1 substrates such as chlorzoxazone, p
      nitrophenol, acetaminophen, and acetone. CYP2E1-humanized mice will be of great
      value for delineating the role of human CYP2E1 in ethanol-induced oxidative
      stress and alcoholic liver damage. They will also function as an important in
      vivo tool for predicting drug metabolism and disposition and drug-drug
      interactions of chemicals that are substrates for human CYP2E1.

PMID- 15576448
TI  - Mechanisms of arsenite-mediated decreases in benzo[k]fluoranthene-induced human
      cytochrome P4501A1 levels in HepG2 cells.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and heavy metals are often environmental
      cocontaminants that could interact to alter PAH carcinogenicity. The heavy metal,
      arsenite, and the PAH, benzo[k]fluoranthene, were used as prototypes to
      investigate, in human HepG2 cells, mechanisms whereby the bioactivation of
      benzo[k]fluoranthene by human CYP1A1 could be diminished by arsenite-mediated
      decreases in CYP1A1 induction by benzo[k]fluoranthene. To determine whether
      arsenite down-regulates CYP1A1 transcription, quantitative real-time reverse
      transcriptase-polymerase chain reaction assays and luciferase reporter gene
      expression assays were used with HepG2 cells treated with benzo[k]fluoranthene
      and arsenite, separately and as a mixture. Benzo[k]fluoranthene (0.5 microM) and
      arsenite (5 microM) markedly decreased benzo[k]fluoranthene-mediated induction of
      CYP1A1 mRNA by 45%. Plasmids containing the CYP1A1 promoter region (pHu-1A1-FL)
      were induced 7.4-fold over vehicle by benzo[k]fluoranthene (0.5 microM), whereas
      arsenite (1, 2.5, or 5 microM) decreased reporter gene expression by 46%, 45%,
      and 61%, respectively. The plasmid, pHu-1A1-Delta100-FL, lacked xenobiotic
      response element (XRE) sites at -1061 and -981 and showed greater responsiveness
      relative to pHu-1A1-FL, by 1.7-fold. Benzo[k]fluoranthene (0.5 microM) and
      arsenite (1, 2.5, or 5 microM) decreased reporter gene expression by 0%, 27%, and
      39%, respectively, relative to expression levels produced by benzo[k]fluoranthene
      alone. Arsenite is stable for at least 48 h in the HepG2 cell medium with respect
      to its ability to diminish CYP1A1 benzo[k]fluoranthene induction. Arsenite did
      not affect benzo[k]fluoranthene induction directly through XRE sites, nor did it
      affect the stability of CYP1A1 mRNA. Thus, arsenite affects the transcriptional
      regulation of the benzo[k]fluoranthene-mediated induction of CYP1A1 and could
      diminish PAH carcinogenicity by decreasing bioactivation by CYP1A1.

PMID- 15576449
TI  - Charge immobilization of the voltage sensor in domain IV is independent of sodium
      current inactivation.
AB  - Recovery from fast inactivation in voltage-dependent Na+ channels is associated
      with a slow component in the time course of gating charge during repolarization
      (i.e. charge immobilization), which results from the slow movement of the S4
      segments in domains III and IV (S4-DIII and S4-DIV). Previous studies have shown
      that the non-specific removal of fast inactivation by the proteolytic enzyme
      pronase eliminated charge immobilization, while the specific removal of fast
      inactivation (by intracellular MTSET modification of a cysteine substituted for
      the phenylalanine in the IFM motif, ICMMTSET, in the inactivation particle formed
      by the linker between domains III and IV) only reduced the amount of charge
      immobilization by nearly one-half. To investigate the molecular origin of the
      remaining slow component of charge immobilization we studied the human cardiac
      Na+ channel (hH1a) in which the outermost arginine in the S4-DIV, which
      contributes approximately 20% to total gating charge (Qmax), was mutated to a
      cysteine (R1C-DIV). Gating charge could be fully restored in R1C-DIV by exposure
      to extracellular MTSEA, a positively charged methanethiosulphonate reagent. The
      RIC-DIV mutation was combined with ICMMTSET to remove fast inactivation, and the
      gating currents of R1C-DIV-ICM(MTSET) were recorded before and after modification
      with MTSEAo. Prior to MTSEAo, the time course of the gating charge during
      repolarization (off-charge) was best described by a single fast time constant.
      After MTSEA, the off-charge had both fast and slow components, with the slow
      component accounting for nearly 35% of Qmax. These results demonstrate that the
      slow movement of the S4-DIV during repolarization is not dependent upon the
      normal binding of the inactivation particle.

PMID- 15576450
TI  - Impaired synaptic scaling in mouse hippocampal neurones expressing NMDA receptors
      with reduced calcium permeability.
AB  - NMDA receptors (NMDARs) play a crucial role for the acquisition of functional
      AMPARs during Hebbian synaptic plasticity at cortical and hippocampal synapses
      over a short timescale of seconds to minutes. In contrast, homeostatic synaptic
      plasticity can occur over longer timescales of hours to days. The induction
      mechanisms of this activity-dependent synaptic scaling are poorly understood but
      are assumed to be independent of NMDAR signalling in the cortex. Here we
      investigated in the hippocampus a potential role of NMDAR-mediated Ca(2+) influx
      for synaptic scaling of AMPA currents by genetic means. The Ca(2+) permeability
      of NMDARs was reduced by selective postnatal expression in principal neurones of
      mouse forebrain half of the NR1 subunits with an amino acid substitution at the
      critical channel site (N598R). This genetic manipulation did not reduce the total
      charge transfer via NMDARs in nucleated patches (somatic) and at synaptic sites.
      In contrast, the current amplitude and the charge carried through AMPARs were
      substantially reduced at somatic and synaptic sites in juvenile and adult
      mutants, indicating persistent downscaling of AMPA responses. Smaller and less
      frequent AMPA miniature currents in the mutant demonstrated a postsynaptic locus
      of this down-regulation. Afferent innervation and release probability were
      unchanged at CA3-to-CA1 synapses of mutants, as judged from input-output and
      minimal stimulation experiments. Our results indicate that NMDAR-mediated Ca(2+)
      signalling is important for synaptic scaling of AMPA currents in the hippocampus
      in vivo.

PMID- 15576451
TI  - Control of muscle glucose uptake: test of the rate-limiting step paradigm in
      conscious, unrestrained mice.
AB  - The aim of this study was to test whether in fact glucose transport is rate
      limiting in control of muscle glucose uptake (MGU) under physiological
      hyperinsulinaemic conditions in the conscious, unrestrained mouse. C57Bl/6J mice
      overexpressing GLUT4 (GLUT4(Tg)), hexokinase II (HK(Tg)), or both (GLUT4(Tg) +
      HK(Tg)), were compared to wild-type (WT) littermates. Catheters were implanted
      into a carotid artery and jugular vein for sampling and infusions at 4 month of
      age. After a 5-day recovery period, conscious mice underwent one of two protocols
      (n = 8-14/group) after a 5-h fast. Saline or insulin (4 mU kg(-1) min(-1)) was
      infused for 120 min. All mice received a bolus of 2-deoxy[(3)H]glucose (2-(3)HDG)
      at 95 min. Glucose was clamped at approximately 165 mg dl(-1) during insulin
      infusion and insulin levels reached approximately 80 microU ml(-1). The rate of
      disappearance of 2-(3)HDG from the blood provided an index of whole body glucose
      clearance. Gastrocnemius, superficial vastus lateralis and soleus muscles were
      excised at 120 min to determine 2-(3)HDG-6-phosphate levels and calculate an
      index of MGU (R(g)). Results show that whole body and tissue-specific indices of
      glucose utilization were: (1) augmented by GLUT4 overexpression, but not HKII
      overexpression, in the basal state; (2) enhanced by HKII overexpression in the
      presence of physiological hyperinsulinaemia; and (3) largely unaffected by GLUT4
      overexpression during insulin clamps whether alone or combined with HKII
      overexpression. Therefore, while glucose transport is the primary barrier to MGU
      under basal conditions, glucose phosphorylation becomes a more important barrier
      during physiological hyperinsulinaemia in all muscles. The control of MGU is
      distributed rather than confined to a single rate-limiting step such as glucose
      transport as glucose transport and phosphorylation can both become barriers to
      skeletal muscle glucose influx.

PMID- 15576452
TI  - The influence of contraction amplitude and firing history on spike-triggered
      averaged trapezius motor unit potentials.
AB  - The spike-triggered averaged (STA) technique was used to examine trapezius motor
      unit potentials and their dependence on contraction amplitude and firing history.
      Individual motor unit firings were identified by a fine-wire intramuscular
      electrode, while STA-derived potentials were extracted from the simultaneously
      recorded surface electromyographic (SEMG) signal. Amplitude-controlled
      contractions and contractions with typing tasks and mental stress were carried
      out. STA potentials were mostly derived from 20 s intervals of firing. Motor unit
      synchrony was estimated by peristimulus time histograms (PSTHs). An association
      between SEMG amplitude and STA-derived motor unit potentials was found: motor
      unit area showed a four-fold increase when SEMG amplitude increased from 1.5 to
      10.5% of the root mean square-detected SEMG signal at maximal voluntary
      contraction (%EMG(max)). Low- and higher threshold motor unit potentials, all
      with recruitment thresholds <10% EMG(max), had similar area at the same
      contraction amplitude. A significant increase in the STA-derived potentials was
      observed after 3 min of constant-amplitude contractions; however, this difference
      was reduced after 10 min and no longer present after 30 min of contraction. Motor
      unit synchrony accounted for, on average, 2.8% additional firings within 2 ms of
      the triggering motor unit. We conclude that the increase in STA-derived
      potentials with contraction amplitude is, to a major extent, due to motor unit
      synchrony, limiting the applicability of this method in postural muscles
      presenting wide motor unit potentials. The similar area of motor units at same
      SEMG amplitude may indicate that trapezius motor units recruited below 10%
      EMG(max) are of similar size and thus not organized according to the Henneman
      size principle.

PMID- 15576453
TI  - Functional properties and pharmacological inhibition of ASIC channels in the
      human SJ-RH30 skeletal muscle cell line.
AB  - The rhabdomyosarcoma cell line (SJ-RH30) exhibits both ultrastructural and
      electrophysiological hallmarks of mammalian skeletal muscle. We have used patch
      clamp electrophysiology to study acid-gated currents in these cells. At a holding
      potential of -60 mV, rapid application of extracellular solutions of pH 6.5
      produced inward current responses in approximately 85% of cells. The amplitude of
      these responses exhibited a marked pH dependence. In addition, the kinetics of
      both activation and desensitization were faster at more acidic pH, whereas the
      deactivation rate was pH independent. Repeated applications of a pH 6.0 solution
      produced a tachyphalaxis that could be substantially attenuated by reducing the
      duration of the acid challenge and increasing the interstimulus interval. The
      current-voltage relationship of the acid-induced currents was linear at positive
      potentials but an area of negative slope conductance was observed in the negative
      potential range. This was not eliminated by removal of extracellular Ca(2+), a
      manoeuvre which did, however, substantially increase current amplitude. Changing
      the transmembrane Na(+) gradient altered the current-voltage relationship in a
      fashion commensurate with an underlying conductance predominantly permeable to
      Na(+). Pharmacologically, acid-induced currents were blocked 84.4 +/- 1.2% by 30
      microm amiloride and 91.8 +/- 3.0% by a 1 : 1000 dilution of Psalmopoeus
      cambridgei venom. Inhibition by both agents could be reversed by a short period
      of compound washout. By contrast, APETx2 had no significant effect on acid-evoked
      currents. These observations strongly suggest the acid-induced current is
      mediated by ASIC1 channels. In agreement with this, current responses of SJ-RH30
      cells to a pH 6.0 challenge were greatly enhanced by extracellular lactate. These
      data demonstrate the presence of ASIC1 channels in a cell line with skeletal
      muscle characteristics. In addition, significant levels of ASIC1 and ASIC3 mRNA
      were found in skeletal muscle tissue samples. These findings are discussed with
      regard to the role such a conductance might play if present in skeletal muscle in
      vivo.

PMID- 15576454
TI  - Sympathetic neural inhibition of conducted vasodilatation along hamster feed
      arteries: complementary effects of alpha1- and alpha2-adrenoreceptor activation.
AB  - Vasodilatation initiated on arterioles of skeletal muscle ascends into the
      proximal feed arteries through cell-to-cell conduction along the endothelium and
      into smooth muscle. Whereas perivascular sympathetic nerve activity (SNA) can
      inhibit conducted vasodilatation and restrict muscle blood flow, the signalling
      events mediating this interaction are poorly defined. Therefore, using isolated
      pressurized (75 mmHg) feed arteries (diameter (microm) at rest = 53 +/- 3;
      maximum = 99 +/- 2; n = 86) of the hamster retractor muscle, we tested the
      hypothesis that distinct yet complementary signalling pathways underlie the
      ability of SNA to inhibit conduction. Conducted vasodilatation was initiated
      using ACh microiontophoresis (1 microA; 250, 500 and 1000 ms) and SNA was
      initiated using local field stimulation (30-50 V; 1 ms at 2, 8 and 16 Hz). With
      vasodilatations of 5-20 microM, conduction increased with ACh pulse duration and
      was inhibited progressively as the frequency of SNA increased. During SNA,
      conduction was partially restored with inhibition of alpha1- (0.1 microM
      prazosin) or alpha2- (0.1 microM RX821002) adrenoreceptors and fully restored
      with both antagonists present. Activating alpha1- (50 nM phenylephrine) or alpha2
      (1 microM UK 14,304) adrenoreceptors inhibited conduction partially and their
      simultaneous activation inhibited conduction cumulatively (P < 0.05). Elevated
      [K+]o (30 or 40 mM) or phorbol esters (0.5 microM) also inhibited conduction yet
      similar constriction with l-NNA (50 microM) or Bay K 8644 (10 nM) did not. Thus,
      the activation of alpha1- and alpha2-adrenoreceptors inhibits conducted
      vasodilatation through complementary signalling events. With robust coupling
      along the endothelium, our modelling predicts that the inhibition of conduction
      by SNA can be explained by reduced electrical coupling through myoendothelial gap
      junctions or greater current leak across smooth muscle cell membranes.

PMID- 15576455
TI  - Expression and function of bradykinin B1 and B2 receptors in normal and inflamed
      rat urinary bladder urothelium.
AB  - The bladder urothelium exhibits dynamic sensory properties that adapt to changes
      in the local environment. These studies investigated the localization and
      function of bradykinin receptor subtypes B1 and B2 in the normal and inflamed
      (cyclophosphamide (CYP)-induced cystitis) bladder urothelium and their
      contribution to lower urinary tract function in the rat. Our findings indicate
      that the bradykinin 2 receptor (B2R) but not the bradykinin 1 receptor (B1R) is
      expressed in control bladder urothelium. B2R immunoreactivity was localized
      throughout the bladder, including the urothelium and detrusor smooth muscle.
      Bradykinin-evoked activation of this receptor elevated intracellular calcium
      (EC(50) = 8.4 nM) in a concentration-related manner and evoked ATP release from
      control cultured rat urothelial cells. In contrast, B1R mRNA was not detected in
      control rat urinary bladder; however, following acute (24 h) and chronic (8 day)
      CYP-induced cystitis in the rat, B1R mRNA was detected throughout the bladder.
      Functional B1Rs were demonstrated by evoking ATP release and increases in
      [Ca(2+)](i) in CYP (24 h)-treated cultured rat urothelial cells with a selective
      B1 receptor agonist (des-Arg(9)-bradykinin). Cystometry performed on control
      anaesthetized rats revealed that intravesical instillation of bradykinin
      activated the micturition pathway. Attenuation of this response by the P2
      receptor antagonist PPADS suggests that bradykinin-induced micturition
      facilitation may be due in part to increased purinergic responsiveness. CYP (24
      h)-treated rats demonstrated bladder hyperactivity that was significantly reduced
      by intravesical administration of either B1 (des-Arg(10)-Hoe-140) or B2 (Hoe-140)
      receptor antagonists. These studies demonstrate that urothelial expression of
      bradykinin receptors is plastic and is altered by pathology.

PMID- 15576456
TI  - Structural and functional characteristics of the Val44Met insulin-like growth
      factor I missense mutation: correlation with effects on growth and development.
AB  - We have previously described the phenotype resulting from a missense mutation in
      the IGF-I gene, which leads to expression of IGF-I with a methionine instead of a
      valine at position 44 (Val44Met IGF-I). This mutation caused severe growth and
      mental retardation as well as deafness evident at birth and growth retardation in
      childhood, but is relatively well tolerated in adulthood. We have conducted a
      biochemical and structural analysis of Val44Met IGF-I to provide a molecular
      basis for the phenotype observed. Val44Met IGF-I exhibits a 90-fold decrease in
      type 1 IGF receptor (IGF-1R) binding compared with wild-type human IGF-I and only
      poorly stimulates autophosphorylation of the IGF-1R. The ability of Val44Met IGF
      I to signal via the extracellular signal-regulated kinase 1/2 and Akt/protein
      kinase B pathways and to stimulate DNA synthesis is correspondingly poorer.
      Binding or activation of both insulin receptor isoforms is not detectable even at
      micromolar concentrations. However, Val44Met IGF-I binds IGF-binding protein-2
      (IGFBP-2), IGFBP-3, and IGFBP-6 with equal affinity to IGF-I, suggesting the
      maintenance of overall structure, particularly in the IGFBP binding domain.
      Structural analysis by nuclear magnetic resonance confirms retention of near
      native structure with only local side-chain disruptions despite the significant
      loss of function. To our knowledge, our results provide the first structural
      study of a naturally occurring mutant human IGF-I associated with growth and
      developmental abnormalities and identifies Val44 as an essential residue involved
      in the IGF-IGF-1R interaction.

PMID- 15576457
TI  - The endogenous growth hormone secretagogue (ghrelin) is synthesized and secreted
      by chondrocytes.
AB  - Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), is a
      recently isolated hormone, prevalently expressed in stomach but also in other
      tissues such as hypothalamus and placenta. This novel acylated peptide acts at a
      central level to stimulate GH secretion and, notably, to regulate food intake.
      However, the existence of further, as yet unknown, effects or presence of ghrelin
      in peripheral tissues cannot be ruled out. In this report, we provide clear
      evidence for the expression of ghrelin peptide and mRNA in human, mouse, and rat
      chondrocytes. Immunoreactive ghrelin was identified by immunohistochemistry in
      rat cartilage, being localized prevalently in proliferative and maturative zone
      of the epiphyseal growth plate, and in mouse and human chondrocytic cell lines.
      Moreover, ghrelin mRNA was detected by RT-PCR and confirmed by Southern analysis
      in rat cartilage as well as in mouse and human chondrocytes cell lines. Ghrelin
      mRNA expression has been studied in rat along early life development showing a
      stable profile of expression throughout. Although ghrelin expression in
      chondrocytes suggests the presence of an unexpected autocrine/paracrine pathway,
      we failed to identify the functional GH secretagogue receptor type 1A by RT-PCR.
      On the other hand, binding analysis with 125I ghrelin suggests the presence of
      specific receptors different from the 1A isotype. Scatchard analysis revealed the
      presence of two receptors with respectively high and low affinity. Finally,
      ghrelin, in vitro, was able to significantly stimulate cAMP production and
      inhibits chondrocytes metabolic activity both in human and murine chondrocytes.
      In addition, ghrelin is able to actively decrease both spontaneous or insulin
      induced long chain fatty acid uptake in human and mouse chondrocytes. This study
      is the first to provide evidence for the presence of this novel peptide in
      chondrocytes and suggests novel potential roles for this newly recognized
      component of the GH axis in cartilage metabolism.

PMID- 15576458
TI  - Dexamethasone induces apoptosis in proliferative chondrocytes through activation
      of caspases and suppression of the Akt-phosphatidylinositol 3'-kinase signaling
      pathway.
AB  - Although glucocorticoids are known to induce apoptosis in chondrocytes, the
      mechanisms for this effect and the potential antiapoptotic role of IGF-I are
      unknown. To address this, we studied the effects of dexamethasone (Dexa) on
      apoptosis in the HCS-2/8 chondrocytic cell line. Dexa (25 microm) increased
      apoptosis (cell death ELISA) by 39% and 45% after 48 and 72 h, respectively (P <
      0.01 and P < 0.05, respectively). IGF-I (100 ng/ml) decreased Dexa-induced
      apoptosis to levels similar to control cells. Apoptosis was associated with
      cleavage of poly-ADP-ribose polymerase (PARP) and alpha-fodrin and activation of
      caspases-8, -9, and -3 (Western), an effect that was counteracted when
      chondrocytes were cocultured with Dexa + IGF-I. Inhibitors for caspases-8, -9,
      and -3 (50 microm each) equally suppressed Dexa-induced apoptosis (P < 0.01).
      Time-response experiments showed that caspase-8 was activated earlier (at 12 h)
      than caspase-9 (at 36 h). We studied the phosphatidylinositol 3'-kinase (PI3K)
      pathway to further investigate the mechanisms of Dexa-induced apoptosis. Dexa
      decreased Akt phosphorylation by 93% (P < 0.001) without affecting total Akt and
      increased the p85alpha subunit 4-fold. The Akt inhibitor SH-6 (10 microm)
      increased apoptosis by 54% (P < 0.001). When combining Dexa with SH-6, apoptosis
      was not further increased, showing that Dexa-induced apoptosis is mediated
      through inhibition of the PI3K pathway. Addition of IGF-I to SH-6- or Dexa + SH-6
      treated cells decreased apoptosis by 21.2% (P < 0.001) and 20.6% (P < 0.001),
      respectively. We conclude that Dexa-induced apoptosis is caspase dependent with
      an early activation of caspase-8. IGF-I can rescue chondrocytes from Dexa-induced
      apoptosis partially through the activation of other pathways than the PI3K
      signaling pathway. Based on our in vitro data, we speculate that in vivo
      treatment with glucocorticoids may diminish longitudinal growth by increasing
      apoptosis of proliferative growth plate chondrocytes.

PMID- 15576459
TI  - Tamoxifen stimulates cancellous bone formation in long bones of female mice.
AB  - Selective estrogen receptor modulators (SERMs) have been developed as a means of
      targeting estrogen's protective effect on the skeleton in the treatment of
      postmenopausal osteoporosis. Although it is well established that SERMs such as
      tamoxifen inhibit bone resorption in a similar manner to estrogen, whether this
      agent shares estrogen's stimulatory action on bone formation is currently
      unclear. To address this question, we compared the effect of treatment for 28 d
      with 17beta-estradiol (E2; 0.1, 1.0 mg/kg x d) and tamoxifen (0.1, 1.0, or 10
      mg/kg x d) on cancellous bone formation at the proximal tibial metaphysis of
      intact female mice. E2 stimulated the formation of new cancellous bone throughout
      the metaphysis. A similar response was observed after administration of
      tamoxifen, the magnitude of which was approximately 50% of that seen after E2. As
      expected, E2 was found to suppress longitudinal bone growth, but in contrast,
      this parameter was stimulated by tamoxifen. We conclude that tamoxifen acts as an
      agonist with respect to estrogen's stimulatory action on bone formation but as an
      antagonist in terms of estrogen's inhibition of longitudinal growth, suggesting
      that the protective effect of SERMs on the skeleton is partly mediated by
      stimulation of osteoblast activity.

PMID- 15576460
TI  - Adrenomedullin is both proinflammatory and antiinflammatory: its effects on gene
      expression and secretion of cytokines and macrophage migration inhibitory factor
      in NR8383 macrophage cell line.
AB  - Adrenomedullin (ADM) is a potent vasorelaxant peptide that plays important roles
      in cardiovascular homeostasis and inflammatory response. ADM derived from
      macrophages is one of the major sources of ADM that is produced in the
      inflammatory process. To assess the functions of ADM in inflammation, we studied
      the temporal changes in ADM production and its effect on secretion of macrophage
      migration inhibitory factor (MIF) and cytokine response of NR8383 rat macrophages
      activated by lipopolysaccharide (LPS). NR8383 cells were stimulated by LPS in the
      absence and presence of exogenous ADM, and the concentrations of ADM, MIF, and
      proinflammatory cytokines (IL-6, TNF-alpha, and IL-1beta) in the culture media
      and gene expressions of the cells were measured. We confirmed that the secretion
      and mRNA expression of ADM in the macrophages were markedly increased by LPS. ADM
      increased initial secretion of MIF and IL-1beta from both nonstimulated and LPS
      stimulated cells, and it also increased basal and LPS-induced IL-6 secretion of
      the cells by 2- to 15-fold. However, it reduced secretion of TNF-alpha from LPS
      stimulated cells by 34-56%. Our results suggest that ADM modulates MIF secretion
      and cytokine production and plays important roles in both the initiation and
      propagation of the inflammatory response.

PMID- 15576461
TI  - Mitogen-activated protein kinase mediates luteinizing hormone-induced breakdown
      of communication and oocyte maturation in rat ovarian follicles.
AB  - Resumption of meiosis, induced by LH, is preceded by the breakdown of gap
      junctional communication, which terminates the supply of cAMP from the somatic
      cells of the ovarian follicle to the oocyte. It has recently been shown that LH
      induced reinitiation of meiosis is mediated by MAPK; however, the underlying
      molecular mechanism involved in the action of this enzyme remains unknown. We
      hypothesized that activation of MAPK interrupts junctional communication within
      the ovarian follicle, leading, in turn, to oocyte maturation. To test this
      hypothesis, we blocked the activation of MAPK by UO126, which specifically
      inhibits the MAPK signaling pathway. We analyzed junctional communication using
      three complementary methods: 1) patch-clamp analysis, which determined changes in
      the electrical coupling between two adjacent granulosa cells; 2) the scrape
      loading technique, which monitored the spread of dyes through a granulosa cell
      layer; and 3) a metabolic coupling assay, which evaluated the transfer of
      radiolabeled uridine from the cumulus cells to the oocyte. We show, herein, that
      the somatic follicle cells, rather than the oocyte, activate MAPK immediately
      after their exposure to LH. Moreover, inhibition of LH-induced MAPK activation
      not only prevents oocyte maturation but also blocks the reduction in junctional
      communication. In addition, the appearance of the two phosphorylated forms of the
      gap junction protein, connexin 43, in response to LH, was avoided by UO126. We
      concluded that MAPK mediates LH-induced oocyte maturation by interrupting cell-to
      cell communication within the ovarian follicle, possibly through phosphorylation
      of connexin 43.

PMID- 15576462
TI  - Production and release of macrophage migration inhibitory factor from human
      adipocytes.
AB  - BACKGROUND AND AIM OF THE STUDY: Macrophage migration inhibitory factor (MIF) has
      been identified as a critical mediator of inflammatory responses. Because of its
      potent migration inhibition activity, it regulates macrophage accumulation in
      tissues. We therefore analyzed whether human adipocytes produce MIF, in the
      search of candidate mediators of macrophage infiltration of obese adipose tissue.
      METHODS: Human adipose tissue samples were obtained from various depots. The
      precursor cells were allowed to differentiate under defined adipogenic culture
      conditions. MIF expression was analyzed by RT-PCR, ELISA, and
      immunocytochemistry. RESULTS: Human preadipocytes secreted MIF in a
      differentiation-dependent fashion with maximum concentrations at d 12, whereas
      MIF mRNA was detected in both undifferentiated and differentiated cells at
      relatively constant levels. Immunocytochemical analysis showed that MIF protein
      was present in preadipocytes and more pronounced in differentiated adipocytes.
      Freshly isolated mature adipocytes from sc, omental, and mammary depots released
      MIF at rates of up to 10,000 pg/ml.24 h. Most importantly, MIF production was
      positively correlated with donor body mass index. Secretion of MIF was not
      influenced by lipopolysaccharide, interferon-gamma, or IL-4. The rates of MIF
      release from sc and omental adipocytes were similar but approximately 10 times
      higher compared with mammary adipocytes. CONCLUSIONS: Human preadipocytes and
      mature adipocytes from different depots spontaneously release substantial amounts
      of MIF. Expression levels were positively associated with donor body mass index.
      Hence, MIF may be an obesity-dependent mediator of macrophage infiltration of
      adipose tissue.

PMID- 15576463
TI  - Activation of the mammalian target of rapamycin pathway acutely inhibits insulin
      signaling to Akt and glucose transport in 3T3-L1 and human adipocytes.
AB  - The mammalian target of rapamycin (mTOR) pathway has recently emerged as a
      chronic modulator of insulin-mediated glucose metabolism. In this study, we
      evaluated the involvement of this pathway in the acute regulation of insulin
      action in both 3T3-L1 and human adipocytes. Insulin rapidly (t(1/2) = 5 min)
      stimulated the mTOR pathway, as reflected by a 10-fold stimulation of 70-kDa
      ribosomal S6 kinase 1 (S6K1) activity in 3T3-L1 adipocytes. Inhibition of
      mTOR/S6K1 by rapamycin increased insulin-stimulated glucose transport by as much
      as 45% in 3T3-L1 adipocytes. Activation of mTOR/S6K1 by insulin was associated
      with a rapamycin-sensitive increase in Ser636/639 phosphorylation of insulin
      receptor substrate (IRS)-1 but, surprisingly, did not result in impaired IRS-1
      associated phosphatidylinositol (PI) 3-kinase activity. However, insulin-induced
      activation of Akt was increased by rapamycin. Insulin also activated S6K1 and
      increased phosphorylation of IRS-1 on Ser636/639 in human adipocytes. As in
      murine cells, rapamycin treatment of human adipocytes inhibited S6K1, blunted
      Ser636/639 phosphorylation of IRS-1, leading to increased Akt activation and
      glucose uptake by insulin. Further studies in 3T3-L1 adipocytes revealed that
      rapamycin prevented the relocalization of IRS-1 from the low-density membranes to
      the cytosol in response to insulin. Furthermore, inhibition of mTOR markedly
      potentiated the ability of insulin to increase PI 3,4,5-triphosphate levels
      concomitantly with an increased phosphorylation of Akt at the plasma membrane,
      low-density membranes, and cytosol. However, neither GLUT4 nor GLUT1
      translocation induced by insulin were increased by rapamycin treatment. Taken
      together, these results indicate that the mTOR pathway is an important modulator
      of the signals involved in the acute regulation of insulin-stimulated glucose
      transport in 3T3-L1 and human adipocytes.

PMID- 15576464
TI  - Interaction between the interferon signaling pathway and the human glucocorticoid
      receptor gene 1A promoter.
AB  - The newly described 1A promoter of the human glucocorticoid receptor (hGR) gene
      contains an interferon (IFN) regulatory factor element (IRF-E), a binding motif
      for the family of proteins termed IFN regulatory factors (IRFs) that are
      regulated by IFNs. To examine the in vivo role of IFNs in hGR gene regulation,
      human T cell lines (CEM-C7 and Jurkat) were treated with IFN gamma. IFN gamma
      rapidly induces the expression of IRF-1 proteins in a dose- and time-dependent
      manner. Luciferase expression is induced by IFN treatment in Jurkat cells
      transfected with an hGR 1A promoter IRF-E/luciferase reporter gene, but induction
      is lost with deletion of the IRF-E. Electrophoretic mobility shift and supershift
      analyses indicate an increase in the binding of IRF-1 to oligonucleotides
      containing the hGR 1A promoter IRF-E after IFN gamma treatment, whereas IRF-2
      binding to this oligonucleotide is unchanged. Human IRF-1 and IRF-2 proteins
      expressed in Chinese hamster ovary cells bind to the hGR 1A promoter IRF-E;
      however, only IRF-1 activates transcription. Although IFNs clearly activate a
      transfected reporter gene containing the hGR 1A promoter in T cells, they do not
      alter the sensitivity of CEM-C7 cells to glucocorticoid-induced apoptosis.
      Additional studies revealed that the glucocorticoid steroid hormone,
      dexamethasone (DEX), completely blocks IFN induction of IRF-1 mRNA levels. This
      could explain the lack of any greater apoptotic response to a combination of DEX
      plus IFN compared with the response to DEX alone. In addition, treatment with IFN
      gamma alone does not alter endogenous GR mRNA levels (including exon 1A
      containing transcripts derived from the hGR 1A promoter) in T lymphoblast cells,
      even though IRF-1 levels are induced. The difference in IRF-1-driven
      transcription between the hGR 1A reporter construct and the endogenous hGR 1A
      promoter could potentially be due to epigenetic effects, such as methylation.

PMID- 15576465
TI  - Protein-caloric food restriction affects insulin-like growth factor system in
      fetal Wistar rat.
AB  - We have previously shown that fetuses from protein-caloric undernourished
      pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 d
      post coitum exhibit increased beta-cell mass. This alteration is correlated with
      increased insulinemia and total pancreatic insulin content, a pattern similar to
      that reported in infants of mild diabetic mothers. In this work, we investigated
      in undernourished fetuses: 1) whether availability of growth factors such as
      insulin, GH, and IGFs and their binding proteins (IGFBPs) could be implicated in
      this alteration, and 2) the beta-cell mitogenic response to IGFs in vitro. The
      results show that maternal undernutrition increases pancreatic IGF-I expression
      and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I
      expression and serum IGF-I levels were decreased. No changes were observed in
      serum IGF-II, and its expression was diminished in undernourished pancreases and
      unchanged in the liver, compared with control fetuses. Serum levels and liver and
      pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished
      fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in
      pancreas were increased. Finally, the beta-cell mitogenic response to IGFs in
      vitro was significantly increased in undernourished fetal islets, compared with
      controls. In conclusion, in undernourished fetuses the increased beta-cell mass
      can be related to the stimulation of replicative beta-cell response due to
      locally increased pancreatic IGF-I mRNA; this effect is perhaps potentiated or
      favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene
      expression.

PMID- 15576466
TI  - Maternal protein intake is not associated with infant blood pressure.
AB  - BACKGROUND: Animal data show that low protein intake in pregnancy programs higher
      offspring blood pressure, but similar data in humans are limited. We examined the
      associations of first and second trimester maternal protein intake with offspring
      blood pressure (BP) at the age of six months. METHODS: In a prospective US cohort
      study, called Project Viva, pregnant women completed validated semi-quantitative
      food-frequency questionnaires (FFQ) to measure gestational protein intake. Among
      947 mother-offspring pairs with first trimester dietary data and 910 pairs with
      second trimester data, we measured systolic blood pressure (SBP) up to five times
      with an automated device in the offspring at the age of six months. Controlling
      for blood pressure measurement conditions, maternal and infant characteristics,
      we examined the effect of energy-adjusted maternal protein intake on infant SBP
      using multivariable mixed effects models. RESULTS: Mean daily second trimester
      maternal protein intake was 17.6% of energy (mean 2111 kcal/day). First trimester
      nutrient intakes were similar. Mean SBP at age 6 months was 90.0 mm Hg (SD 12.9).
      Consistent with prior reports, adjusted SBP was 1.94 mm Hg lower [95% confidence
      interval (CI) -3.45 to -0.42] for each kg increase in birth weight. However, we
      did not find an association between maternal protein intake and infant SBP. After
      adjusting for covariates, the effect estimates were 0.14 mm Hg (95% CI 20.12 to
      20.40) for a 1% increase in energy from protein during the second trimester, and
      20.01 mm Hg (95% CI 20.24 to -0.23) for a 1% increase in energy from protein in
      the first trimester. CONCLUSIONS: Variation in maternal total protein intake
      during pregnancy does not appear to program offspring blood pressure.

PMID- 15576467
TI  - Cohort Profile: the Whitehall II study.

PMID- 15576468
TI  - Significance of cyclooxygenase-2 induced via p38 mitogen-activated protein kinase
      in mechanical stimulus-induced peritoneal adhesion in mice.
AB  - Postoperative peritoneal adhesion represents a major complication of surgery, but
      the molecular mechanism underlying pathogenesis of adhesion is not fully
      understood. The present study investigated the roles of cyclooxygenase (COX)-1
      and COX-2 in peritoneal adhesion induced by scraping the surface of the cecum and
      abdominal wall in mice. Slight, but macroscopically observable, peritoneal
      adhesion was induced even on day 1, and the extent of adhesion reached a maximum
      on day 7 and beyond. COX-1 mRNA was constitutively expressed in the intact cecum,
      and its expression level was not altered after the mechanical stimulus. In
      contrast, expression of the COX-2 gene was markedly increased after the stimulus,
      and maximum expression was observed on days 3 to 7. Mofezolac, a specific COX-1
      inhibitor, had no effect on peritoneal adhesion at 30 mg/kg and had only marginal
      effects on prostaglandin (PG)E2 levels in the cecum or peritoneal fluid. On the
      other hand, two highly selective inhibitors for COX-2, NS-398 (N-[2
      (cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide) and CAY10404 [3-(4
      methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole], dose-dependently
      inhibited both adhesion formation and the increase in PGE2 levels (3-30 mg/kg).
      The effects of NS-398 were eliminated when PGE2 or (R)-butaprost was administered
      exogenously. A COX-2 antisense oligonucleotide also attenuated adhesion
      formation. Activation of p38 mitogen-activated protein (MAP) kinase was observed
      in the traumatized cecum, and an MAP kinase inhibitor, SB202190 [4-(4
      fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole], inhibited adhesion
      formation (54% inhibition at 15 microM) and also reduced the COX-2 mRNA level and
      PGE2 levels. In conclusion, COX-2, but not COX-1, plays a significant role in
      mechanical stimulus-induced peritoneal formation in the mouse cecum.

PMID- 15576469
TI  - Modulation of sarcoplasmic reticulum function by Na+/K+ pump inhibitors with
      different toxicity: digoxin and PST2744 [(E,Z)-3-((2-aminoethoxy)imino)androstane
      6,17-dione hydrochloride].
AB  - OBJECTIVE: To gain some insight on the lesser arrhythmogenic properties of
      PST2744 [(E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride]
      compared with digoxin, we compared modulation of intracellular Ca2+ dynamics by
      the two agents. METHODS: SERCA (sarcoplasmic reticulum Ca2+-ATPase) activity and
      Ca2+ leak rate were measured in sarcoplasmic reticulum (SR) vesicles from guinea
      pig ventricles. Membrane current, intracellular Ca2+, and twitch amplitude were
      evaluated in guinea pig ventricular myocytes with or without blockade of the
      Na+/Ca2+ exchanger. RESULTS: In SR vesicles, PST2744 (30-300 nM), but not
      digoxin, increased SERCA activity; digoxin only (> or =0.1 nM) increased SR Ca2+
      leak. In myocytes with blocked Na+/Ca2+ exchanger, Ca2+ reloading of caffeine
      depleted SR was enhanced by PST2744 and slightly inhibited by digoxin. In
      myocytes with functioning Na+/Ca2+ exchanger, both agents increased diastolic
      Ca2+, SR Ca2+ content, the gain of Ca2+-induced Ca2+ release, the rate of
      cytosolic Ca2+ decay, twitch amplitude, and relaxation rate. Consistent with the
      observations in SR vesicles, the effects on SR Ca2+ content and Ca2+ decay rate
      were significantly larger for PST2744 than for digoxin. CONCLUSIONS: In isolated
      SR vesicles, PST2744 and digoxin directly affected SR function in opposite ways;
      this could be reproduced in myocytes during Na+/Ca2+ exchanger blockade. Under
      physiological conditions (functioning Na+/Ca2+ exchanger), the two agents
      affected Ca2+ dynamics in the same direction, as expected by their Na+/K+ pump
      inhibition; however, differential SR modulation was still expressed by
      quantitative differences. Thus, the more favorable inotropy-to-toxicity ratio
      previously described for PST2744 appears to be associated with direct SERCA
      stimulation and/or lack of enhancement of Ca2+ leak.

PMID- 15576470
TI  - Does cyclic AMP mediate rat urinary bladder relaxation by isoproterenol?
AB  - Cyclic AMP is the prototypical second messenger of beta-adrenergic receptors, but
      recent findings have questioned its role in mediating smooth muscle relaxation
      upon beta-adrenergic receptor stimulation. We have investigated the signaling
      mechanisms underlying beta-adrenergic receptor-mediated relaxation of rat urinary
      bladder. Concentration-response curves for isoproterenol-induced bladder
      relaxation were generated in the presence or absence of inhibitors, with
      concomitant experiments using passive tension and KCl-induced precontraction. The
      adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536;
      1 microM), the protein kinase A inhibitors 1-(5-isoquinolinesulfonyl)-2
      methylpiperazine (H7; 10 microM), N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide (H89; 1 microM), and Rp-adenosine 3',5'-cyclic
      monophosphorothioate (Rp-cAMPS; 30 microM), and the guanylyl cyclase inhibitor 1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 3 microM) produced only minor if
      any inhibition of relaxation against passive tension or KCl-induced
      precontraction. Among various potassium channel inhibitors, BaCl2 (10 microM),
      tetraethylammonium (3 microM), apamin (300 nM), and glibenclamide (10 microM) did
      not inhibit isoproterenol-induced relaxation. Some inhibition of the
      isoproterenol effects against KCl-induced tone but not against passive tension
      was seen with inhibitors of calcium-dependent potassium channels such as
      charybdotoxin and iberiotoxin (30 nM each). A combination of SQ 22,536 and ODQ
      significantly inhibited relaxation against passive tension by about half, but not
      that against KCl-induced tone. Moreover, the combination failed to enhance
      inhibition by charybdotoxin against KCl-induced tone. We conclude that cAMP and
      cGMP each play a minor role in beta-adrenergic receptor-mediated relaxation
      against passive tension, and calcium-dependent potassium channels play a minor
      role against active tension.

PMID- 15576471
TI  - A novel benzodiazepine selectively inhibits keratinocyte proliferation and
      reduces retinoid-induced epidermal hyperplasia in organ-cultured human skin.
AB  - Bz-423 is a new benzodiazepine that has cytotoxic and cytostatic effects against
      a number of cell types in culture, and recent studies have shown efficacy in
      experimental lupus models in rodents. The present study demonstrates that
      treating human skin in organ culture with Bz-423 suppresses retinoid-induced
      epidermal hyperplasia. Bz-423 suppresses hyperplasia in organ culture at
      concentrations that also inhibit keratinocyte proliferation in monolayer culture
      but that are not cytotoxic for keratinocytes and do not inhibit fibroblast
      growth. Under conditions in which keratinocyte proliferation is inhibited, there
      is no measurable effect on epidermal growth factor receptor activation, but there
      is reduced signaling at the level of extracellular signal-regulated kinase 1/2
      mitogen-activated protein kinase. Suppression of keratinocyte growth by Bz-423 is
      associated with generation of intracellular oxidants. However, antioxidant
      treatment reduces keratinocyte cytotoxicity that occurs at high concentrations of
      Bz-423, but it does not inhibit growth suppression. Together, these data suggest
      that Bz-423 has the potential to limit the untoward effects associated with
      topical retinoid treatment, and in addition, may have therapeutic effects against
      other forms of epidermal hyperplasia.

PMID- 15576472
TI  - CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through
      binding integrin counterreceptors on endothelial cells.
AB  - CD97, a membrane protein expressed at high levels on inflammatory cells and some
      carcinomas, is a member of the adhesion G protein-coupled receptor family, whose
      members have bipartite structures consisting of an extracellular peptide
      containing adhesion motifs noncovalently coupled to a class B 7-transmembrane
      domain. CD97alpha, the extracellular domain of CD97, contains 3 to 5 fibrillin
      class 1 epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD)
      tripeptide, and a mucin stalk. We show here that CD97alpha promotes angiogenesis
      in vivo as demonstrated with purified protein in a directed in vivo angiogenesis
      assay (DIVAA) and by enhanced vascularization of developing tumors expressing
      CD97. These data suggest that CD97 can contribute to angiogenesis associated with
      inflammation and tumor progression. Strong integrin alpha5beta1 interactions with
      CD97 have been identified, but alpha v beta3 also contributes to cell attachment.
      Furthermore, soluble CD97 acts as a potent chemoattractant for migration and
      invasion of human umbilical vein endothelial cells (HUVECs), and this function is
      integrin dependent. CD97 EGF-like repeat 4 is known to bind chondroitin sulfate.
      It was found that coengagement of alpha5beta1 and chondroitotin sulfate
      proteoglycan by CD97 synergistically initiates endothelial cell invasion.
      Integrin alpha5beta1 is the first high-affinity cellular counterreceptor that has
      been identified for a member within this family of adhesion receptors.

PMID- 15576473
TI  - Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique
      expression pattern and Ca(2+)-dependent association with annexin VI.
AB  - We generated a murine monoclonal antibody (B28p) detecting an antigenic
      determinant shared by the immunoglobulin superfamily receptor translocation
      associated 1 (IRTA1) receptor (the immunogen used to raise B28p) and an unrelated
      28-kDa protein that was subsequently subjected to extensive characterization. The
      expression of the 28-kDa protein in normal lymphohematopoietic tissues was
      restricted to B cells and plasma cells and clearly differed from that expected
      for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue [MALT]
      marginal zone B cells). Two-dimensional polyacrylamide gel electrophoresis (2D
      PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor
      protein D52 (TPD52), whose expression had been previously described only in
      normal and neoplastic epithelia. Specific B28p reactivity with TPD52 was
      confirmed by immunostaining/immunoblotting of TPD52-transfected cells. TPD52
      expression pattern in normal and neoplastic B cells was unique. In fact, unlike
      other B-cell molecules (paired box 5 [PAX5], CD19, CD79a, CD20, CD22), which are
      down-regulated during differentiation from B cells to plasma cells, TPD52
      expression reached its maximum levels at the plasma cell stage. In the Thiel
      myeloma cell line, TPD52 bound to annexin VI in a Ca(2+)-dependent manner,
      suggesting that these molecules may act in concert to regulate secretory
      processes in plasma cells, similarly to what was observed in pancreatic acinar
      cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for
      the diagnosis of B-cell malignancies.

PMID- 15576474
TI  - Genetic complementation reveals a novel human congenital disorder of
      glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid
      transporter.
AB  - We have identified a homozygous G>A substitution in the donor splice site of
      intron 6 (IVS6 + 1G>A) of the cytidine monophosphate (CMP)-sialic acid
      transporter gene of Lec2 cells as the mutation responsible for their asialo
      phenotype. These cells were used in complementation studies to test the activity
      of the 2 CMP-sialic acid transporter cDNA alleles of a patient devoid of sialyl
      Le(x) expression on polymorphonuclear cells. No complementation was obtained with
      either of the 2 patient alleles, whereas full restoration of the sialylated
      phenotype was obtained in the Lec2 cells transfected with the corresponding human
      wild-type transcript. The inactivation of one patient allele by a double
      microdeletion inducing a premature stop codon at position 327 and a splice
      mutation of the other allele inducing a 130-base pair (bp) deletion and a
      premature stop codon at position 684 are proposed to be the causal defects of
      this disease. A 4-base insertion in intron 6 was found in the mother and is
      proposed to be responsible for the splice mutation. We conclude that this defect
      is a new type of congenital disorder of glycosylation (CDG) of type IIf affecting
      the transport of CMP-sialic acid into the Golgi apparatus.

PMID- 15576475
TI  - Phenotypic correction and long-term expression of factor VIII in hemophilic mice
      by immunotolerization and nonviral gene transfer using the Sleeping Beauty
      transposon system.
AB  - Hemophilia A is a lead candidate for treatment by gene therapy because small
      increments in the missing secreted protein product, coagulation factor VIII
      (FVIII), would result in substantial clinical amelioration. Clinically relevant
      therapy might be achieved by stably delivering a human FVIII cDNA to correct the
      bleeding disorder. We used the Sleeping Beauty (SB) transposon, delivered as
      naked plasmid DNA by tail-vein injection, to integrate B-domain-deleted FVIII
      genes into the chromosomes of hemophilia A mice and correct the phenotype. Since
      FVIII protein is a neoantigen to these mice, sustaining therapeutic plasma FVIII
      levels was problematic due to inhibitory antibody production. We circumvented
      this problem by tolerizing 82% of neonates by a single facial-vein injection of
      recombinant FVIII within 24 hours of birth (the remaining 18% formed inhibitors).
      Achievement of high-level (10%-100% of normal) FVIII expression and phenotypic
      correction required co-injection of an SB transposase-expressing plasmid to
      facilitate transgene integration in immunotolerized animals. Linker-mediated
      polymerase chain reaction was used to clone FVIII transposon insertion sites from
      liver genomic DNA, providing molecular evidence of transposition. Thus, SB
      provides a nonviral means for sustained FVIII gene delivery in a mouse model of
      hemophilia A if the immune response is prevented.

PMID- 15576476
TI  - High expression of cyclin B1 predicts a favorable outcome in patients with
      follicular lymphoma.
AB  - Substantial research has been dedicated to the study of the relationship between
      genetic mechanisms regulating cell functions in tumors and how those tumors
      respond to various treatment regimens. Because these mechanisms are still not
      well understood, we have chosen to study the genetic makeup of 57 tumor samples
      from patients with follicular lymphoma (FL). Our goal was to develop a prognostic
      tool, which can be used as an aid in determining FL patients with tumors
      genetically predisposed to a successful treatment with the CHOP
      (cyclophosphamide, vincristine, doxorubicin, prednisone) regimen. To select
      relevant genes, high-density oligonucleotide arrays were used. There were 14
      genes highly expressed in FL patients that responded well to CHOP chemotherapy,
      and 11 of these were involved in G2/M transition of the cell cycle, in mitosis,
      or in DNA modulation. A high expression of CCNB1 (cyclin B1), CDC2, CDKN3A,
      CKS1B, ANP32E, and KIAA0101, but not of the proliferation-related antigen Ki-67,
      was associated with better survival rate in a univariate analysis. CCNB1
      expression had an independent prognostic value when included in a multivariate
      analysis together with the 5 parameters of the follicular lymphoma international
      prognostic index.

PMID- 15576477
TI  - Immunohistochemical profiling of caspase signaling pathways predicts clinical
      response to chemotherapy in primary nodal diffuse large B-cell lymphomas.
AB  - We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL)
      to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling
      pathways predicts clinical outcome. Expression levels of cellular FLICE
      inhibitory protein (c-Flip) and numbers of active caspase 3-positive lymphoma
      cells were used to determine the status of the caspase 8-mediated pathway.
      Expression levels of Bcl-2 and X-linked inhibitor of apoptosis (XIAP) were used
      to determine the status of the caspase 9-mediated pathway. Expression of c-Flip,
      XIAP, Bcl-2, and caspase 3 activity all provided prognostic information.
      According to these immunohistochemical parameters, inhibition of either or both
      caspase signaling pathways was detected in all patients. Three groups of patients
      were identified, one with a caspase 8 inhibition profile, one with caspase 8 and
      9 inhibition profiles, and one with a caspase 9 inhibition profile. Caspase 9
      inhibition was strongly associated with poor response to chemotherapy and usually
      with fatal outcome, whereas caspase 8 inhibition was associated with excellent
      clinical outcome. Thus, our data strongly suggest that inhibition of the caspase
      9-mediated pathway, but not the caspase 8-mediated pathway, is a major cause for
      therapy resistance in patients with nodal DLBCL.

PMID- 15576478
TI  - Single infusion of myeloid progenitors reduces death from Aspergillus fumigatus
      following chemotherapy-induced neutropenia.
AB  - Hematopoietic progenitors committed to the myeloid lineage, the common myeloid
      and granulocyte-monocyte progenitors (CMP/GMP), have been shown to protect
      against opportunistic pathogens following myeloablative radiation; however, the
      efficacy of this approach has not been studied in the setting of chemotherapy
      induced neutropenia. In this mouse model, the infusion of CMP/GMP on the day
      after 5-fluorouracil (5-FU) administration (D+1) resulted in a significant
      increase in the number of splenic neutrophils by D+8 when compared with 5-FU-only
      controls (P = .02), the majority of which were CMP/GMP-derived (54%). Moreover,
      19% and 28% of neutrophils in the blood and bone marrow, respectively, were
      CMP/GMP-derived. Survival following intranasal challenge with the fungus
      Aspergillus fumigatus was significantly higher in CMP/GMP-infused mice than the
      controls (56% and 33% respectively; P = .019). Thus, a single infusion of CMP/GMP
      enhances tissue neutrophil content and increases survival against a lethal
      challenge with A fumigatus in the setting of chemotherapy-induced neutropenia.

PMID- 15576479
TI  - Leydig cell injury as a consequence of an acute graft-versus-host reaction.
AB  - Hematopoietic stem cell transplantation (HSCT) is associated with significant
      posttransplantation gonadotoxicity. This deficit has been mainly attributed to
      pretransplantation conditioning, but lower sperm counts in humans also appear to
      be associated with graft-versus-host disease (GVHD) following allogeneic HSCT.
      However, the mechanisms leading to diminished spermatocyte levels during GVHD
      remain unknown. Here we demonstrate that injury to intratesticular cells occurs
      in unconditioned F1 mice following the infiltration of donor alloreactive T cells
      during an acute graft-versus-host reaction (GVHR). Using computer-aided
      quantitative microscopic morphometry we demonstrate that the nadir of Leydig cell
      volume density coincides with the peak of intratesticular infiltration by donor T
      cells. Injury to Leydig cells correlates with an intratesticular inflammatory
      response characterized by interferon-gamma and tumor necrosis factor-alpha
      production. These results demonstrate impairment of testosterone-producing Leydig
      cells during a local alloresponse, thus representing a mechanism that contributes
      to gonadal insufficiency following allogeneic HSCT.

PMID- 15576480
TI  - Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal
      cord: a potential mechanism for neurodegeneration in multiple sclerosis and
      spinal cord injury.
AB  - Dysfunction and death of spinal cord neurons are critical determinants of
      neurological deficits in various pathological conditions, including multiple
      sclerosis (MS) and spinal cord injury. Yet, the molecular mechanisms underlying
      neuronal/axonal damage remain undefined. Our previous studies raised the
      possibility that a decrease in the levels of plasma membrane calcium ATPase
      isoform 2 (PMCA2), a major pump extruding calcium from neurons, promotes neuronal
      pathology in the spinal cord during experimental autoimmune encephalomyelitis
      (EAE), an animal model of MS, and after spinal cord trauma. However, the causal
      relationship between alterations in PMCA2 levels and neuronal injury was not well
      established. We now report that inhibition of PMCA activity in purified spinal
      cord neuronal cultures delays calcium clearance, increases the number of
      nonphosphorylated neurofilament H (SMI-32) immunoreactive cells, and induces
      swelling and beading of SMI-32-positive neurites. These changes are followed by
      activation of caspase-3 and neuronal loss. Importantly, the number of spinal cord
      motor neurons is significantly decreased in PMCA2-deficient mice and the
      deafwaddler(2J), a mouse with a functionally null mutation in the PMCA2 gene. Our
      findings suggest that a reduction in PMCA2 level or activity leading to delays in
      calcium clearance may cause neuronal damage and loss in the spinal cord.

PMID- 15576481
TI  - Phospholipid transfer protein (PLTP) deficiency reduces brain vitamin E content
      and increases anxiety in mice.
AB  - Vitamin E supplementation constitutes a promising strategy in the prevention of
      neurodegenerative diseases. Here, we show that a phospholipid transfer protein
      (PLTP) is widely expressed in the brain where it appears to function as a
      transfer factor for alpha-tocopherol, the main isomer of vitamin E. PLTP
      deficiency results in significant depletion of brain alpha-tocopherol in both
      homozygous (-30.1%, P<0.0002) and heterozygous (-18.0%, P<0.05) PLTP knocked-out
      mice. Alpha-tocopherol depletion in PLTP-deficient homozygotes is associated with
      the elevation of lipofuscin (+25% and +450% increases in cortex and substantia
      nigra, respectively), cholesterol oxides (+54.5%, P<0.05), and cellular peroxides
      (+32.3%, P<0.01) in the brain. Complete PLTP deficiency in homozygotes is
      accompanied by increased anxiety as shown by fewer entries (8.3% vs. 44.4% in
      controls, P<0.01) and less time spent (1.7% vs. 41.3% in controls, P<0.05) in the
      open arms of an elevated plus-maze, in the absence of locomotor deterioration.
      Thus, the vitamin E transfer activity of PLTP appears to be a key process in
      preventing oxidative damage in the brain, and PLTP-deficient mice could be a new
      model of the contribution of oxidative brain injury in the etiology of
      neurodegenerative diseases.

PMID- 15576482
TI  - Isoprostanes: markers and mediators of oxidative stress.
AB  - Some years ago it was discovered that prostaglandin F2-like compounds are formed
      in vivo by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid.
      Because these compounds are a series of isomers that contain the prostane ring of
      prostaglandins, they were termed F2-isoprostanes. Intermediates in the
      isoprostane pathway are prostaglandin H2-like compounds that become reduced to
      form F2-isoprostanes but also undergo rearrangement in vivo to form E2-, D2-, A2
      , J2-isoprostanes, isothromboxanes, and highly reactive gamma-ketoaldehydes,
      termed isoketals. Analogous compounds have also been shown to be formed from free
      radical mediated oxidation of docosoahexaenoic acid. Because docosahexaenoic acid
      is highly enriched in neurons, these compounds have been termed neuroprostanes
      and neuroketals. An important aspect of the discovery of isoprostanes is that
      measurement of F2-isoprostanes has emerged as one of the most reliable approaches
      to assess oxidative stress status in vivo, providing an important tool to explore
      the role of oxidative stress in the pathogenesis of human disease. Measurement of
      F4-neuroprostanes has also proved of value in exploring the role of oxidative
      stress in neurodegenerative diseases. Products of the isoprostane pathway have
      been found to exert potent biological actions and therefore may participate as
      physiological mediators of disease.

PMID- 15576483
TI  - A role for caveolae in cell migration.
AB  - Caveolae are specialized plasma membrane subdomains capable of transport and
      sophisticated compartmentalization of cell signaling. Numerous cell functions,
      including cell type-specific functions, involve caveolae and require caveolin-1,
      the major protein component of these organelles. Caveolae are particularly
      abundant in endothelial cells and participate in endothelial transcytosis,
      vascular permeability, vasomotor tone control, and vascular reactivity. Caveolin
      1 drives the formation of plasma membrane caveolae and anchors them to the actin
      cytoskeleton, modulates cell interaction with the extracellular matrix, pulls
      together and regulates signaling molecules, and transports cholesterol. Via these
      functions, caveolin-1 might play an important role in cell movement through
      control of cell membrane composition and membrane surface expansion, polarization
      of signaling molecules and matrix proteolysis, and/or cytoskeleton remodeling.
      Caveolae and caveolin-1 are polarized in migrating endothelial cells, indicating
      they may play a role in cell motility. Several studies have shown that
      manipulation of caveolin-1 expression affects cell migration in a complex way. We
      are reviewing the current data and hypotheses in favor of an essential role for
      caveolae in cell migration.

PMID- 15576484
TI  - Antagonism of RAGE suppresses peripheral nerve regeneration.
AB  - Axotomy of peripheral nerve triggers events that coordinate a limited
      inflammatory response to axonal degeneration and initiation of neurite outgrowth.
      Inflammatory and neurite outgrowth-promoting roles for the receptor for advanced
      glycation end products (RAGE) have been suggested, so we tested its role in
      peripheral nerve regeneration. Analysis of immunohistochemical localization of
      RAGE by confocal microscopy revealed that RAGE was expressed in axons and
      infiltrating mononuclear phagocytes upon unilateral sciatic nerve crush in mice.
      Administration of soluble RAGE, the extracellular ligand binding domain of RAGE,
      or blocking F(ab')2 fragments of antibodies raised to either RAGE or its ligands,
      S100/calgranulins or amphoterin, reduced functional recovery as assessed by motor
      and sensory nerve conduction velocities and sciatic functional index and reduced
      regeneration, as assessed by myelinated fiber density after acute crush of the
      sciatic nerve. In parallel, in mice subjected to RAGE blockade, decreased numbers
      of mononuclear phagocytes infiltrated the distal nerve segments after crush.
      These findings provide the first evidence of an innate function of the
      ligand/RAGE axis and suggest that RAGE plays an important role in regeneration of
      the peripheral nervous system.

PMID- 15576485
TI  - RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory
      and axonal outgrowth pathways.
AB  - Axotomy of peripheral nerve stimulates events in multiple cell types that
      initiate a limited inflammatory response to axonal degeneration and simultaneous
      outgrowth of neurites into the distal segments after injury. We found that
      pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice
      subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies
      revealed that RAGE was expressed in axons and in infiltrating mononuclear
      phagocytes upon injury, we tested the role of RAGE in these distinct cell types
      on nerve regeneration. Transgenic mice expressing signal transduction-deficient
      RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected
      to unilateral crush injury to the sciatic nerve. Transgenic mice displayed
      decreased functional and morphological recovery compared with littermate
      controls, as assessed by motor and sensory conduction velocities; and myelinated
      fiber density. In double transgenic mice expressing signal transduction deficient
      RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even
      further impaired, suggesting the critical interplay between RAGE-modulated
      inflammation and neurite outgrowth in nerve repair. These findings suggest that
      RAGE signaling in inflammatory cells and peripheral neurons plays an important
      role in plasticity of the peripheral nervous system.

PMID- 15576486
TI  - Bcl-XL disrupts death-inducing signal complex formation in plasma membrane
      induced by hypoxia/reoxygenation.
AB  - Hypoxia/reoxygenation (H/R) causes cellular injury and death. The cell death
      pathways induced by H/R remain incompletely understood. H/R can induce Bid and
      Bax mitochondrial translocation and cytochrome c release. Using mouse lung
      endothelial cells (MLEC), we examined the role of Bcl-X(L), an anti-apoptotic Bcl
      2-related protein, in H/R-induced cell death. The expression of Bcl-X(L)
      protected MLEC against H/R-induced cell death by blocking Bax and Bid
      translocation and inhibiting mitochondrial cytochrome c release. Bcl-X(L)
      expression inhibited caspase-8 cleavage and death-inducing signal complex (DISC)
      formation in plasma membrane. By isolating mitochondrial, nuclear, and Golgi
      fractions, we found that H/R induced DISC formation in these organelles. Bcl-X(L)
      expression inhibited DISC formation in the nuclear and Golgi fractions relative
      to LacZ-infected controls. In contrast, DISC formation was elevated in the
      mitochondrial fraction of Bcl-X(L)-infected cells. GRASP65, a Golgi-associated
      protein, physically associated with Fas and caspase-8; Bcl-X(L) expression
      decreased these associations. Bcl-X(L) expression also up-regulated FLIP, a
      caspase-8 inhibitor. In conclusion, Bcl-X(L) may inactivate caspase-8 by
      decreasing DISC formation in the plasma membrane, nucleus, and Golgi complex
      while diverting DISC formation to the mitochondria. The inhibitory effects of Bcl
      X(L) on DISC formation may play significant roles in protecting endothelial cells
      from H/R-induced cell death.

PMID- 15576487
TI  - Functional genomic analysis of the ADP-ribosylation factor family of GTPases:
      phylogeny among diverse eukaryotes and function in C. elegans.
AB  - ADP-ribosylation factor (Arf) and Arf-like (Arl) proteins are a family of highly
      conserved 21 kDa GTPases that emerged early in the evolution of eukaryotes. These
      proteins serve regulatory roles in vesicular traffic, lipid metabolism,
      microtubule dynamics, development, and likely other cellular processes. We found
      evidence for the presence of 6 Arf family members in the protist Giardia lamblia
      and 22 members in mammals. A phylogenetic analysis was performed to delineate the
      evolutionary relationships among Arf family members and to attempt to organize
      them by both their evolutionary origins and functions in cells and/or organisms.
      The approximately 100 protein sequences analyzed from animals, fungi, plants, and
      protists clustered into 11 groups, including Arfs, nine Arls, and Sar proteins.
      To begin functional analyses of the family in a metazoan model organism, we
      examined roles for all three C. elegans Arfs (Arf-1, Arf-3, and Arf-6) and three
      Arls (Arl-1, Arl-2, and Arl-3) by use of RNA-mediated interference (RNAi).
      Injection of double-stranded RNA (dsRNA) encoding Arf-1 or Arf-3 into N2
      hermaphrodites produced embryonic lethality in their offspring and, later,
      sterility in the injected animals themselves. Injection of Arl-2 dsRNA resulted
      in a disorganized germline and sterility in early offspring, with later offspring
      exhibiting an early embryonic arrest. Thus, of the six Arf family members
      examined in C. elegans, at least three are required for embryogenesis. These data
      represent the first analysis of the role(s) of multiple members of this family in
      the development of a multicellular organism.

PMID- 15576488
TI  - Histopathological and cognitive defects induced by Nef in the brain.
AB  - Complex mechanisms of human immunodeficiency virus type-1 (HIV-1) brain
      pathogenesis suggest the contribution of individual HIV-1 gene products. Among
      them, the Nef protein has been reported to harbor a major determinant of
      pathogenicity in AIDS-like disease. The goal of the present study was to
      determine whether Nef protein expressed in vivo by primary macrophages could
      induce a brain toxicity also affecting the behavior of the rat. To achieve this
      goal we grafted Nef-transduced macrophages into the rat hippocampus. Two months
      post-transplantation, we observed that Nef induces monocyte/macrophage
      recruitment, expression of TNF-alpha, and astrogliosis. No apoptotic event was
      detected. We further demonstrated that Nef neurotoxicity is associated with
      cognitive deficits.

PMID- 15576489
TI  - Targeting extracellular pyrophosphates underpins the high selectivity of nisin.
AB  - The spread of infectious diseases and the increase in antibiotic resistance
      represent a life-threatening global development that calls for new approaches to
      control microorganisms. Of all potential targets, the essential and unique
      pathway of bacterial cell wall synthesis, targeted by the first known antibiotic
      penicillin, remains a perfect candidate for the development of new antibiotics.
      Here we show that the lantibiotic nisin exercises its antibacterial action by
      targeting peptidoglycan intermediates' extracellular pyrophosphate, unique to
      bacterial cell wall precursors. We show that nisin sequesters cell wall
      precursors found in the outer leaflet of bacterial plasma membranes, Lipid II and
      undecaprenyl pyrophosphate, into stable complexes. We propose a model of
      antibacterial action for nisin in which the terminal amino group of Ile1 targets
      the pyrophosphate groups of the bacterial cell wall precursors, where it docks
      via a hydrogen bond. The pyrophosphate moiety, a highly conserved chemical group
      different from the L-Lys-D-Ala-D-Ala docking motif for vancomycin, has no
      biochemical analogs with comparable properties and is unlikely to be susceptible
      to bacterial adaptations akin to those responsible for resistance to penicillins
      and vancomycin.

PMID- 15576490
TI  - Obesity-related leptin regulates Alzheimer's Abeta.
AB  - Abeta peptide is the major proteinateous component of the amyloid plaques found
      in the brains of Alzheimer's disease (AD) patients and is regarded by many as the
      culprit of the disorder. It is well documented that brain lipids are intricately
      involved in Abeta-related pathogenic pathways. An important modulator of lipid
      homeostasis is the pluripotent peptide leptin. Here we demonstrate leptin's
      ability to modify Abeta levels in vitro and in vivo. Similar to methyl-beta
      cyclodextrin, leptin reduces beta-secretase activity in neuronal cells possibly
      by altering the lipid composition of membrane lipid rafts. This phenotype
      contrasts treatments with cholesterol and etomoxir, an inhibitor of carnitine
      palmitoyl transferase-1. Conversely, inhibitors of acetyl CoA carboxylase and
      fatty acid synthase mimicked leptin's action. Leptin was also able to increase
      apoE-dependent Abeta uptake in vitro. Thus, leptin can modulate bidirectional
      Abeta kinesis, reducing its levels extracellularly. Most strikingly, chronic
      administration of leptin to AD-transgenic animals reduced the brain Abeta load,
      underlying its therapeutic potential.

PMID- 15576491
TI  - Novel role of microtubules in thrombin-induced endothelial barrier dysfunction.
AB  - Disturbances in endothelial cell (EC) barrier regulation are critically dependent
      upon rearrangements of EC actin cytoskeleton. However, the role of microtubule
      (MT) network in the regulation of EC permeability is not well understood. We
      examined involvement of MT remodeling in thrombin-induced EC permeability and
      explored MT regulation by heterotrimeric G12/13 proteins and by small GTPase Rho.
      Thrombin induced phosphorylation of MT regulatory protein tau at Ser409 and
      Ser262 and peripheral MT disassembly, which was linked to increased EC
      permeability. MT stabilization by taxol attenuated thrombin-induced permeability,
      actin remodeling, and paracellular gap formation and diminished thrombin-induced
      activation of Rho and Rho-kinase. Expression of activated Galpha12/13 subunits
      involved in thrombin-mediated signaling or their effector p115RhoGEF involved in
      Rho activation caused MT disassembly, whereas p115RhoGEF-specific negative
      regulator RGS preserved MT from thrombin-induced disassembly. Consistent with
      these results, expression of activated RhoA and Rho-kinase induced MT
      disassembly. Conversely, thrombin-induced disassembly of peripheral MT network
      was attenuated by expression of dominant negative RhoA and Rho-kinase mutants or
      by pharmacological inhibition of Rho-kinase. Collectively, our data demonstrate
      for the first time a critical involvement of MT disassembly in thrombin-induced
      EC barrier dysfunction and indicate G-protein-dependent mechanisms of thrombin
      induced MT alteration.

PMID- 15576492
TI  - Acute myocardial hypoxia increases BNP gene expression.
AB  - It is well established that cardiac failure increases cardiac B-type natriuretic
      peptide (BNP) expression due to myocardial stretching. However, patients with
      ischemic heart disease also display increased plasma BNP and proBNP
      concentrations despite preserved cardiac function. In this study, we examined
      whether acute myocardial hypoxia increases cardiac BNP expression. Surgical
      reduction of the blood flow to an area of the anterior ventricular wall in pigs
      reduced the myocardial oxygen tension from 46 +/- 4 to 13 +/- 5 mmHg. The tissue
      contents of VEGF and BNP mRNA increased 1.8-fold and 3.5-fold, respectively
      (n=10, P<0.005) in hypoxic compared with normoxic ventricular myocardium after
      2.2 +/- 0.2 h; the magnitude of the increase in BNP mRNA expression was
      positively correlated with that of VEGF in hypoxic myocardium (r=0.66, P<0.05).
      In support of a hypoxia-induced increase of BNP gene transcription, the content
      of a premature BNP mRNA was increased in hypoxic myocardium (4.8-fold, P<0.005)
      and in freshly harvested ventricular myocytes when kept in culture flasks and
      oxygen-deprived for 3 h (2.2-fold, P=0.002). ProBNP peptide accumulated in the
      medium of freshly harvested ventricular myocyte cultures but was undetectable in
      ventricular myocardium, indicating rapid release of the newly synthesized proBNP
      peptide. Accordingly, the plasma proBNP concentration increased after 2 h of
      myocardial hypoxia (P=0.028). Cumulatively, the data suggest that acute hypoxia
      stimulates cardiac BNP expression.

PMID- 15576494
TI  - Are techniques used in cognitive behaviour therapy applicable to behaviour change
      interventions based on the theory of planned behaviour?
AB  - The Theory of Planned Behaviour (TPB) is increasingly being used to inform the
      development of interventions to promote health behaviour change. However,
      although the theory can be used to identify the determinants of particular health
      related behaviours, it offers little guidance on how to change these determinants
      and hence how to promote behaviour change. There is evidence that Cognitive
      Behaviour Therapy (CBT) can be used to support health behaviour change. This
      article discusses the similarities and differences between the two approaches,
      and considers whether techniques used in CBT are applicable to interventions
      based on the TPB.

PMID- 15576495
TI  - Integration of two models, or dominance of one?
AB  - Hobbis and Sutton attempted to integrate Cognitive Behavior Therapy (CBT) with
      the Theory of Planned Behavior (TPB). The possibility of such an integration
      portends exciting opportunities since behavioral interventions have had limited
      impact on behavior change. The integration, however, may more easily occur if
      Hobbis and Sutton had selected a formulation of the TPB that incorporated
      emotional variables, which is a primary focus of CBT. Furthermore, more work may
      be necessary to integrate the specific cognitive constructs between CBT and the
      TPB. Empirical research will be necessary to validate that the integration
      occurred in a meaningful way.

PMID- 15576496
TI  - Commentary on Hobbis and Sutton.
AB  - The present commentary highlights and discusses two issues raised by Hobbis and
      Sutton (this issue): the identification of key beliefs, and the methods suggested
      by Cognitive Behaviour Therapy (CBT) for changing beliefs and behaviour. In
      relation to the first issue it is noted how the conception of key beliefs varies
      between the Theory of Planned Behaviour (TPB) and CBT. In relation to the second
      issue it is noted that CBT may well identify a number of useful techniques for
      changing beliefs, although a variety of other techniques may also be useful for
      changing beliefs.

PMID- 15576497
TI  - Theory-based behavior change interventions: comments on Hobbis and Sutton.
AB  - Hobbis and Sutton (this issue) suggest that Cognitive Behavior Therapy (CBT)
      techniques can be used in interventions based on the Theory of Planned Behavior
      (TPB). Although this suggestion has merit, CBT is only one of many applicable
      methods for producing belief and behavior change. Moreover, CBT's primary purpose
      is to help people carry out intended behaviors, not to influence intentions, and
      that it is more useful in face-to-face than in community-level interventions.
      Contrary to Hobbis and Sutton's critique, TPB can accommodate core beliefs or
      fundamental assumptions, but the theory suggests that interventions targeted at
      such beliefs are less effective than interventions targeted at behavior specific
      beliefs.

PMID- 15576498
TI  - Is cognitive behaviour therapy effective for changing health behaviours?
      Commentary on Hobbis and Sutton.
AB  - Although Cognitive Behaviour Therapy (CBT) has successfully combined procedures
      based on behavioural and cognitive theories to reduce emotional problems, there
      is limited research into the efficacy of CBT in changing health behaviours. Of
      the studies cited by Hobbis and Sutton (this issue), only one measured health
      behaviours. In order to evaluate the effectiveness of behaviour change
      techniques, it is essential that the endpoints are behaviours, rather than health
      or emotional outcomes. There are both theoretical and circumstantial reasons for
      believing that CBT may be effective for changing health behaviours. Hobbis and
      Sutton have considered CBT as an addition to the Theory of Planned Behaviour
      based interventions. It may be even more effective as an alternative.

PMID- 15576500
TI  - Inter-role relationships in hospital-based pharmacy and therapeutics committee
      decision making.
AB  - The interdependencies of Pharmacy and Therapeutics Committee members in 222
      teaching hospitals were studied by use of the social relations model.
      Cooperation, influence, frustration and enjoyment were studied among four-person
      subgroups chosen from the five roles recommended for hospitals by the American
      Society of Hospital Pharmacists: physician-chair, physician-nonchair, pharmacist,
      nurse and administrator. The results show that the elicitation and reception of
      cooperation, influence, frustration and enjoyment vary considerably by role (as
      manifest in actor and partner effects); small amounts of individual reciprocity
      (i.e. the association between actor and partner effects) were found for some
      measures of interdependence across roles, while small amounts of dyadic
      reciprocity (i.e. the association between reciprocal relationship effects) were
      found for many relationships. Significant group level (i.e. committee) effects
      were found as well.

PMID- 15576501
TI  - Message framing and pap test utilization among women attending a community health
      clinic.
AB  - In a randomized experiment, women (N = 441) watched either a loss- or gain-framed
      video emphasizing the prevention or detection functions of the Pap test to test
      the hypothesis that loss- and gain-framed messages differentially influence
      health behaviors depending on the risk involved in performing the behavior. As
      predicted, loss-framed messages emphasizing the costs of not detecting cervical
      cancer early (a risky behavior) and gain-framed messages emphasizing the benefits
      of preventing cervical cancer (a less risky behavior) were most persuasive in
      motivating women to obtain a Pap test.

PMID- 15576502
TI  - Contributions of leisure participation in predicting stress coping and health
      among police and emergency response services workers.
AB  - This study examined the extent to which frequency and enjoyment measures of
      leisure participation predict adaptational outcomes, over and above the
      contributions of general coping. Police and emergency response services workers
      (N = 132) participated in the study, and a repeated measures design was used. The
      study provides evidence that the type of leisure activity matters in predicting
      immediate adaptational outcomes (coping effectiveness, coping satisfaction and
      stress reduction) and mental and physical health. Relaxing leisure was found to
      be the strongest positive predictor of coping with stress, while social leisure
      and cultural leisure significantly predicted greater mental or physical health.

PMID- 15576503
TI  - Work-related goal perceptions and affective well-being.
AB  - The aim was to clarify how perceptions of work-related goals influence affective
      well-being and goal commitment. Participants (N = 201) completed a Goal
      Perceptions Questionnaire and affect scales. A model was refined using structural
      equation modelling. Value and success expectation substantially mediated the
      effects of other goal perceptions on affects and commitment. Both value and
      success expectation increased commitment, but whereas value increased positive
      affects, success expectation reduced negative affects. The determinants of value
      (e.g. personal origin) were different from those of success expectation (e.g.
      personal control). Through astute goal setting, it is possible to promote well
      being without compromising commitment.

PMID- 15576504
TI  - Mediation and the construction of contemporary understandings of health and
      lifestyle.
AB  - The practice of using media to promote the benefits of diet and exercise has been
      associated with the rise in prominence of a sense of personal obligation for
      one's own health. This article contributes to recent critiques of the emphasis
      being placed on individual responsibility for health. We argue that if health
      psychologists are to develop an adequately social understanding of our role in
      promoting health, then we must begin to examine the influence of our practices
      and agendas on public understandings. Extracts from research accounts are used to
      illustrate the pervasiveness of media health messages in everyday life and the
      prominence of a sense of individual responsibility.

PMID- 15576505
TI  - 'You sort of switch off': exploring mindlessness in injecting drug users'
      accounts of blood.
AB  - Risk of blood borne virus among injecting drug users is high and is a significant
      challenge for public health efforts. Mindlessness/mindfulness theory provides an
      alternative lens through which to understand social phenomena. Interview
      transcripts of 32 current and former injectors were explored for evidence of
      mindless injecting (or automatic behaviour). Mindlessness in injecting practices
      can be important as opportunities to reduce injecting risk can emerge from
      understanding 'expert' approaches to injecting. Further work is required to
      generate fuller understandings of this construct on injecting drug use and to
      incorporate carefully and sensitively this tool into health promotion efforts.

PMID- 15576506
TI  - Differences in illness representation among pulmonary patients and their
      providers.
AB  - This investigation examined how patient and provider groups represent 11
      descriptors (concepts) of breathing and breathlessness. Two patient groups, those
      with chronic obstructive pulmonary disease (COPD) and those with asthma, and two
      provider groups, pulmonologists and nurse specialists (PNS), rated the
      dissimilarity between each of 55 pairs of concepts on visual analogue scales
      (VAS). The results demonstrate differences between the groups in illness
      representation. The findings have implications for understanding differences in
      illness representation between patient groups and providers.

PMID- 15576507
TI  - The effects of economic disadvantage on psychological well-being and quality of
      life among people with multiple sclerosis.
AB  - This study investigated the impact of economic disadvantage among people with
      multiple sclerosis (MS) on their psychological well-being and quality of life.
      Participants were 113 people with MS (31 males, 82 females). Information was
      obtained on income, lost income, costs of MS, economic pressure, coping,
      psychological well-being and quality of life. Economic pressure, and not actual
      MS-related costs predicted psychological well-being. Costs, economic pressure and
      coping predicted quality of life. These results demonstrate that pressure due to
      changed economic circumstances, as well as coping with these pressures is
      important in the quality of life of people with MS.

PMID- 15576508
TI  - Differences in the folding transition state of ubiquitin indicated by phi and psi
      analyses.
AB  - We compare the folding transition state (TS) of ubiquitin previously identified
      by using psi analysis to that determined by using analysis. Both methods attempt
      to identify interactions and their relative populations at the rate-limiting step
      for folding. The TS ensemble derived from psi analysis has an extensive native
      like chain topology, with a four-stranded beta-sheet network and a portion of the
      major helix. According to analysis, however, the TS is much smaller and more
      polarized, with only a local helix/hairpin motif. We find that structured regions
      can have values far from unity, the canonical value for such sites, because of
      structural relaxation of the TS. Consequently, these sites may be incorrectly
      interpreted as contributing little to the structure of the TS. These results
      stress the need for caution when interpreting and drawing conclusions from
      analysis alone and highlight the need for more specific tools for examining the
      structure and energetics of the TS ensemble.

PMID- 15576509
TI  - Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules
      in intestinal epithelial cells and suppresses early inflammatory responses.
AB  - Vi capsular polysaccharide (Vi) was first identified as a virulence antigen of
      Salmonella typhi, the causative agent of typhoid fever in humans; it renders S.
      typhi resistant to phagocytosis and the action of serum complement. However, the
      role of Vi during the infection of intestinal epithelium with S. typhi is not
      completely understood. We show here that Vi can interact with a model human
      intestinal epithelial cell line, Caco-2, through a cell-surface-associated
      molecular complex containing two major proteins of 30 and 35 kDa and a minor
      protein of approximately 68 kDa. The two major proteins were identified as the
      putative tumor suppressor molecule, prohibitin, and its closely related homolog,
      B cell receptor-associated protein 37. These two proteins were enriched in lipid
      rafts, and Vi readily associated with these membrane microdomains. Engagement of
      Caco-2 cells with Vi inhibited their ability to produce an inflammatory response
      upon infection with Vi(-) S. typhi. Consistent with this effect, infection of
      Caco-2 cells with Vi(+) S. typhi produced less IL-8 compared with Vi(-) S. typhi.
      Cells treated with Vi showed reduced extracellular signal-regulated kinase
      phosphorylation in response to infection with Vi(-) S. typhi or stimulation with
      phorbol 12-myristate 13-acetate, suggesting that the mitogen-activated protein
      kinase pathway might be a target for Vi-mediated inhibition of inflammatory
      responses. These findings reveal a crucial role for Vi in the modulation of early
      inflammatory responses during infection with S. typhi. This kind of a modulation
      could play a significant role in the establishment of infection by S. typhi.

PMID- 15576510
TI  - Unexpected connections between Burnside groups and knot theory.
AB  - In classical knot theory and the theory of quantum invariants substantial effort
      was directed toward the search for unknotting moves on links. We solve, in this
      article, several classical problems concerning unknotting moves. Our approach
      uses a concept, Burnside groups of links, that establishes an unexpected
      relationship between knot theory and group theory. Our method has the potential
      to be used in computational biology in the analysis of DNA via tangle embedding
      theory, as developed by D. W. Sumners [Sumners, D. W., ed. (1992) New Scientific
      Applications of Geometry and Topology (Am Math. Soc., Washington, DC) and Ernst,
      C. & Sumners, D. W. (1999) Math. Proc. Cambridge Philos. Soc. 126, 23-36].

PMID- 15576511
TI  - Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an
      alpha-synuclein rat model of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by a progressive loss of midbrain
      dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies.
      Mutations in several genes including alpha-synuclein and parkin have been linked
      to familial PD. The loss of parkin's E3-ligase activity leads to dopaminergic
      neuronal degeneration in early-onset autosomal recessive juvenile parkinsonism,
      suggesting a key role of parkin for dopamine neuron survival. To evaluate the
      potential neuroprotective role of parkin in the pathogenesis of PD, we tested
      whether overexpression of wild-type rat parkin could protect against the toxicity
      of mutated human A30P alpha-synuclein in a rat lentiviral model of PD. Animals
      overexpressing parkin showed significant reductions in alpha-synuclein-induced
      neuropathology, including preservation of tyrosine hydroxylase-positive cell
      bodies in the substantia nigra and sparing of tyrosine hydroxylase-positive nerve
      terminals in the striatum. The parkin-mediated neuroprotection was associated
      with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a
      key role for parkin in the genesis of Lewy bodies. These results indicate that
      parkin gene therapy may represent a promising candidate treatment for PD.

PMID- 15576512
TI  - Two perfectly conserved arginine residues are required for substrate binding in a
      high-affinity nitrate transporter.
AB  - This study represents the first attempt to investigate the molecular mechanisms
      by which nitrate, an anion of significant ecological, agricultural, and medical
      importance, is transported into cells by high-affinity nitrate transporters. Two
      charged residues, R87 and R368, located within hydrophobic transmembrane domains
      2 and 8, respectively, are conserved in all 52 high-affinity nitrate transporters
      sequenced thus far. Site-directed replacements of either of R87 or R368 residues
      by lysine were found to be tolerated, but such residue changes increased the K(m)
      for nitrate influx from micromolar to millimolar values. Seven other amino acid
      substitutions of R87 or R368 all led to loss of function and lack of growth on
      nitrate. No evidence was obtained of R87 or R368 forming a salt-bridge with
      conserved acidic residues. Remarkably, the phenotype of loss-of-function mutant
      R87T was found to be alleviated by an alteration to lysine of N459, present in
      the second copy of the nitrate signature (transmembrane domain 11), suggesting a
      structural or functional interplay between residues R87 and N459 in the three
      dimensional NrtA protein structure. Failure of the potential reciprocal second
      site suppressor N168K (in the first nitrate signature copy of transmembrane
      domain 5) to revert R368T was observed. Taken with recent structural studies of
      other major facilitator superfamily proteins, the results suggest that R87 and
      R368 are involved in substrate binding and probably located in a region of the
      protein close to N459.

PMID- 15576513
TI  - Use of vasopressin in a canine model of severe verapamil poisoning: a preliminary
      descriptive study.
AB  - OBJECTIVES: The purpose of this preliminary study was to evaluate the effect of
      arginine vasopressin (AVP) administration in a model of shock induced by calcium
      channel antagonist overdose and to determine endogenous serum AVP concentrations
      in calcium channel antagonist-induced shock. METHODS: This was a controlled,
      randomized laboratory investigation based on a previously described canine model
      of verapamil toxicity. After induction of verapamil toxicity, animals in both the
      control and the experimental groups (n = 6 each) received a continuous infusion
      of verapamil. Experimental animals received an escalating dose of AVP, while
      control animals received an equal volume of 0.9% saline infusion. The hemodynamic
      end point was return of mean arterial pressure (MAP) to within 20% of baseline.
      Surviving animals were killed after 60 minutes. RESULTS: In the treatment group,
      administration of low-dose AVP (4 mU/kg/min) resulted in further declines in
      cardiac index and heart rate. No significant change was noted in MAP with low
      dose AVP. A slight increase in MAP was noted with both escalating doses of AVP
      and equivalent volumes of normal saline. By the end of the 60-minute
      antidote/saline phase, the MAPs of the saline control group and the AVP
      experimental group were similar. The primary hemodynamic end point was not
      achieved in either the AVP or the saline control arm. Mean baseline serum AVP
      concentration in control animals was 5.8 pg/mL, increasing to 225 pg/mL during
      the toxicity phase. CONCLUSIONS: In an animal model of verapamil-induced shock,
      endogenous AVP levels increased nearly 40-fold compared with baseline levels.
      Escalating doses of exogenous AVP worsened cardiac index and failed to return MAP
      to within 20% of baseline.

PMID- 15576514
TI  - The validity of chief complaint and discharge diagnosis in emergency department
      based syndromic surveillance.
AB  - OBJECTIVE: Emergency department (ED)-based syndromic surveillance systems are
      being used by public health departments to monitor for outbreaks of infectious
      diseases, including bioterrorism; however, few systems have been validated. The
      authors evaluated a "drop-in" syndromic surveillance system by comparing syndrome
      categorization in the ED with chief complaints and ED discharge diagnoses from
      medical record review. METHODS: A surveillance form was completed for each ED
      visit at 15 participating Arizona hospitals between October 27 and November 18,
      2001. Each patient visit was assigned one of ten clinical syndromes or "none."
      For six of 15 EDs, kappa statistics were used to compare syndrome agreement
      between surveillance forms and syndrome categorization with chief complaint and
      ED discharge diagnosis from medical record review. RESULTS: Overall, agreement
      between surveillance forms and ED discharge diagnoses (kappa = 0.55; 95%
      confidence interval [CI] = 0.52 to 0.59) was significantly higher than between
      surveillance forms and chief complaints (kappa = 0.48; 95% CI = 0.44 to 0.52).
      Agreement between chief complaints and ED discharge diagnoses was poor for
      respiratory tract infection with fever (kappa = 0.33; 95% CI = 0.27 to 0.39).
      Furthermore, pediatric chief complaints showed lower agreement for respiratory
      tract infection with fever when compared with adults (kappa = 0.34 [95% CI = 0.20
      to 0.47] vs. kappa = 0.44 [95% CI = 0.28 to 0.59], respectively). CONCLUSIONS: In
      general, this syndromic surveillance system classified patients into appropriate
      syndrome categories with fair to good agreement compared with chief complaints
      and discharge diagnoses. The present findings suggest that use of ED discharge
      diagnoses, in addition to or instead of chief complaints, may increase
      surveillance validity for both automated and drop-in syndromic surveillance
      systems.

PMID- 15576515
TI  - Efficacy of penicillin for dental pain without overt infection.
AB  - OBJECTIVES: Dental pain is a common presenting symptom in the acute care setting.
      Even in the absence of overt infection, many physicians routinely prescribe
      antibiotics such as penicillin. The authors sought to test the hypothesis that
      penicillin is not necessary or beneficial in the treatment of undifferentiated
      dental pain without overt infection. METHODS: This prospective, randomized,
      double-blind, placebo-controlled trial was conducted at an urban teaching
      hospital with approximately 105,000 emergency department visits per year. A
      convenience sample of adult emergency department patients presenting with dental
      pain and no clinically overt infection was randomized to receive penicillin or
      placebo. A structured evaluation was performed at enrollment and again at a 5- to
      7-day follow-up visit. The main outcome measure was evidence of overt dental
      infection at the 5- to 7-day follow-up visit. RESULTS: A total of 195 patients
      were enrolled. Ninety-eight (50%) were randomized to treatment with penicillin. A
      total of 125 patients (64%) were followed up. Outcome data were identified for
      nine additional study patients, who returned to the dental clinic or emergency
      department outside of the scheduled follow-up period and were included in the
      final analysis. Overall, 13 of 134 patients (9%) developed signs of infection:
      six of 64 (9%) from the penicillin group and seven of 70 (10%) from the placebo
      group (p = 0.90). There was no significant difference between the penicillin and
      placebo groups in baseline characteristics, medication compliance, or visual
      analog scale pain scores at enrollment. CONCLUSIONS: These data support the
      hypothesis that penicillin is neither necessary nor beneficial in the treatment
      of undifferentiated dental pain in the absence of overt infection.

PMID- 15576516
TI  - Impact of a negative evaluation for underlying coronary artery disease on one
      year resource utilization for patients admitted with potential acute coronary
      syndromes.
AB  - Reduction in emergency department (ED) overcrowding is a major Joint Commission
      on the Accreditation of Healthcare Organizations (JCAHO) initiative. One major
      source of ED overcrowding is patients waiting for telemetry beds. OBJECTIVE: To
      determine whether, in patients admitted with a potential acute coronary syndrome,
      a negative evaluation for underlying coronary artery disease would reduce ED and
      hospital revisits over the subsequent year compared with patients who did not
      receive an evaluation for underlying coronary artery disease. METHODS: Nine
      hundred ninety-nine consecutive patients admitted for potential acute coronary
      syndromes through the ED during a one-year period were screened for inclusion.
      Patients who had a negative evaluation for underlying coronary disease were
      compared with patients who were not evaluated for underlying coronary artery
      disease for subsequent ED visits, hospital admissions, and cardiac resource
      utilization over the year following the index visit via a health system-wide
      computerized record review. Patients with positive tests or biomarkers at the
      index visit were excluded. Each repeat visit was rated as "potentially cardiac"
      or "noncardiac." Results of echocardiograms, stress tests, and catheterizations
      and information about in-hospital deaths were obtained. RESULTS: Six hundred
      ninety-two patients met the inclusion criteria: 556 patients received no
      evaluation for underlying coronary artery disease, 116 had a negative stress
      test, and 20 had a negative cardiac catheterization during the index visit.
      Patients with no evaluation for underlying coronary artery disease and patients
      with a negative evaluation had similar likelihoods of a repeat ED visit (negative
      test 39.0% vs. no test 40.3%; p = 0.85) and repeat hospital admission (28.7% vs.
      31.5%; p = 0.61). The rates of a potentially cardiac-related ED visit (21.3 vs.
      23.4%; p = 0.65) and hospital admission (17.7% vs. 20.7%; p = 0.48) were not
      significantly different. The two populations had similar utilization rates of
      echocardiograms, stress tests, and catheterizations (p > 0.70 for all).
      CONCLUSIONS: For patients admitted to the authors' institution with a potential
      acute coronary syndrome, there was no association between a negative evaluation
      for underlying coronary artery disease and overall or potentially cardiac ED
      visits, admissions, or cardiac resource test utilization over the year following
      the index visit.

PMID- 15576517
TI  - Comparison of valdecoxib and an oxycodone-acetaminophen combination for acute
      musculoskeletal pain in the emergency department: a randomized controlled trial.
AB  - Oral opioids are potent analgesics that are used to treat acute pain in the
      emergency department (ED). However, they are associated with adverse events such
      as sedation that may delay safe patient discharge. OBJECTIVE: To compare the
      safety and efficacy of a new cyclooxygenase-2 inhibitor, valdecoxib, with those
      of an oxycodone-acetaminophen combination in patients with acute musculoskeletal
      pain. METHODS: This was a double-blind, randomized controlled trial at an
      immediate care section of a suburban university-based ED with an annual census of
      75,000. Adults with acute musculoskeletal pain without contraindications to the
      study medications were included. After recording their initial pain scores,
      patients were randomized to either oral valdecoxib 40 mg or oxycodone 10 mg with
      acetaminophen 650 mg. Pain scores were recorded at 30 and 60 minutes, and
      patients who requested additional pain relief were given an oral analgesic at the
      physician's discretion. Twenty-four-hour telephone follow-up was performed. The
      pain severity was recorded at 0, 30, and 60 minutes using a validated 100-mm
      visual analog scale marked "most" at the high end. The need for rescue
      medications and the occurrence of adverse events were determined. Study outcomes
      were compared with Student's t-test, repeated-measures analysis of variance
      (ANOVA), and chi(2) tests as appropriate. RESULTS: Fifty-one patients were
      randomized to valdecoxib (26) or oxycodone (25). Mean (+/- SD) age was 36 (+/-
      14.7) years; 49% were women. Pain locations included extremities (49%), neck
      (29%), and back (22%). Baseline patient characteristics and pain severities were
      similar. There was no between-group difference in pain scores at 30 and 60
      minutes. The changes in pain scores over time were also similar in the two study
      groups (repeated-measures ANOVA, p = 0.32). Patients treated with valdecoxib were
      less likely to experience sedation/dizziness (15% vs. 44%, p = 0.03) and to
      require rescue medications within the next 24 hours (44% vs. 74%, p = 0.04).
      CONCLUSIONS: Valdecoxib is as effective as an oxycodone-acetaminophen combination
      in treating ED patients with acute musculoskeletal pain at 30 minutes and less
      likely to cause sedation or the need for rescue analgesia over the next day.

PMID- 15576518
TI  - A multicenter study of depression among emergency department patients.
AB  - OBJECTIVES: The authors sought to determine the 12-month prevalence of depression
      among emergency department (ED) patients using a single-question screen. METHODS:
      This cross-sectional study was conducted in four Boston-area EDs. For two 24-hour
      periods, consecutive patients aged 18 years or older were interviewed, excluding
      those who were severely ill, potential victims of sexual assault, or emotionally
      disturbed. During the interview, patients were asked "Have you had any of the
      following problems during the past 12 months?" Patients answered "yes" or "no" to
      a list of health problems that included depression. In a validation study, the
      authors found that this simple approach correlated well with results from the
      validated Center for Epidemiologic Studies Depression Scale. RESULTS: Of 752
      eligible patients, 539 (72%) were interviewed. Of these patients, 30% (95%
      confidence interval = 26% to 34%) reported depression within the past 12 months.
      Compared with their nondepressed counterparts, depressed patients were more
      likely middle-aged, female, and of lower socioeconomic status. Depressed patients
      were more likely to be smokers and to report a diagnosis of asthma or
      arthritis/rheumatism. In a multivariate analysis, factors that were independently
      associated with depression were lower level of education, smoking, and self
      reported anxiety, chronic fatigue, and back problems. CONCLUSIONS: A 30% 12-month
      prevalence of depression among ED patients was found. Depressed patients had a
      distinct sociodemographic and health profile. In the future, awareness of risk
      factors for depression in the ED setting and use of simple screening instruments
      could aid in the recognition of depression, with subsequent referral to mental
      health services.

PMID- 15576519
TI  - Factors affecting emergency department opioid administration to severely injured
      patients.
AB  - OBJECTIVES: Studies of emergency department (ED) pain management in patients with
      trauma have been mostly restricted to patients with fractures, yet the potential
      for undertreatment of more severely injured patients is great. The authors sought
      to identify factors associated with failure to receive ED opioid administration
      in patients with acute trauma who subsequently required hospitalization. METHODS:
      At an urban Level 1 trauma center and teaching hospital, a retrospective cohort
      study of trauma team activation patients requiring hospitalization between
      January 1 and December 31, 1999, was conducted. The authors excluded patients
      receiving opioids only within ten minutes of chest tube insertion or fracture
      manipulation. The main outcome measure was ED opioid administration. RESULTS: A
      total of 540 charts of hospitalized first-tier trauma team activation patients
      were reviewed. A total of 258 (47.8%) received intravenous opioid analgesia
      within three hours of ED arrival. The median time to receiving the first dose of
      opioids was 95 minutes. Patients were independently less likely to receive
      opioids if they were younger or older, were intubated, had a lower Revised Trauma
      Score, or did not require fracture manipulation. Patients with these factors were
      less likely to receive opioids independent of the amount of time they spent in
      the ED. CONCLUSIONS: Many trauma activation patients requiring hospitalization do
      not receive opioid analgesia in the ED. Patients at particular risk for
      oligoanalgesia include those who are younger or older and those who are more
      seriously injured, as defined by a lower Revised Trauma Score, lower Glasgow Coma
      Scale score, and intubation.

PMID- 15576520
TI  - A low peripheral blood white blood cell count in infants younger than 90 days
      increases the odds of acute bacterial meningitis relative to bacteremia.
AB  - In relying on the peripheral blood white blood cell (WBC) count to identify
      infants at high risk for acute bacterial meningitis and bacteremia, to the best
      of the authors' knowledge, it has not been reported previously whether high and
      low values of the test have similar implications for predicting these separate
      infections. OBJECTIVE: To analyze the relationship between the peripheral WBC
      count and the odds of acute bacterial meningitis relative to bacteremia among
      sick infants aged 3 to 89 days. METHODS: Areas under the receiver operating
      characteristic curve (AUCs) and likelihood ratios at various intervals of the
      total peripheral blood WBC count were computed. RESULTS: A pathogen was isolated
      from blood or cerebrospinal fluid (CSF) from 72 infants aged 3 to 89 days. Fifty
      two infants had growth of a pathogen from the blood only, and 20 had growth from
      the CSF. The most common bacteria isolated were Escherichia coli (32) and group B
      streptococci (32). The AUC for the peripheral WBC count when differentiating
      between acute bacterial meningitis and bacteremia was 0.75 (95% CI = 0.63 to
      0.88). The odds of acute bacterial meningitis relative to bacteremia were
      sevenfold higher for a peripheral WBC cutoff below 5,000 cells/mm(3) and
      threefold lower for a peripheral WBC cutoff at or above 15,000 cells/mm(3).
      CONCLUSIONS: In young infants, the peripheral blood WBC count is useful for
      estimating the odds of acute bacterial meningitis relative to isolated
      bacteremia. A low peripheral blood WBC count should be considered a much more
      worrisome laboratory finding because it is associated with a relatively high risk
      for acute bacterial meningitis relative to the potential for bacteremia.

PMID- 15576521
TI  - Nonurgent emergency department patient characteristics and barriers to primary
      care.
AB  - OBJECTIVE: Nonurgent (NU) emergency department (ED) use is at the forefront of
      medico-political agendas, and diversion of NU patients has been entertained as a
      management strategy. Before policy changes are implemented, this population
      should be better understood with respect to their characteristics and reasons for
      not presenting to primary care providers (PCPs) instead of EDs. This study
      compares NU with urgent and semiurgent (USU) patients and describes the NU
      patients' reasons for not seeking care with a PCP before presenting to the ED.
      METHODS: This was a secondary analysis from a cross-sectional study with
      sequential sampling in the EDs of five Quebec tertiary care hospitals (October
      19, 1999, to May 26, 2000). Data on medical history, social support, awareness
      and utilization of health care, ED visits, referrals, activities of daily living,
      and sociodemographics were obtained. The NU group included patients with triage
      code 5 and the USU group included patients with triage codes 2, 3, and 4 using
      the Canadian Triage and Acuity Scale. Patient characteristics were structured
      into the Andersen behavioral model for health care utilization. RESULTS: Of 2,348
      patients approached, 1,783 patients (77%) were eligible and agreed to
      participate. NU patients (n = 454) were younger than USU patients (n = 1,329)
      (mean age, 43 [SD +/- 18.1] vs. 49 [SD +/- 20.1] years). Patients in the NU group
      had better health (number of prior conditions, 3.1 vs. 3.9), were less likely to
      arrive by ambulance (5% vs. 22%), and were less often admitted from the ED (4%
      vs. 24%). While 70% of NU compared with 75% of USU patients were followed up by a
      PCP, only 22% of NU and 27% of USU patients sought PCP care before presenting to
      the ED. The reasons given by NU patients for not seeking PCP care were
      accessibility (32%), perception of need (22%), referral/follow-up to the ED
      (20%), familiarity with the ED (11%), trust of the ED (7%), and no reason (7%).
      CONCLUSIONS: NU ED patients are different from USU patients and have multiple
      reasons for not seeking primary care before going to the ED. This may help
      explain why various diversion strategies have been unsuccessful and indicate that
      a multifaceted approach may be better suited to this group of patients. The
      design of new interventions, however, will benefit from further research that
      clarifies the impact of NU patients on the health care system.

PMID- 15576522
TI  - Analysis of costs, length of stay, and utilization of emergency department
      services by frequent users: implications for health policy.
AB  - In efforts to decrease emergency department (ED) crowding and health care costs,
      frequent users of ED services have been targeted for interventions to decrease
      their utilization. Previous studies have had different definitions for "frequent
      users" and have considered all frequent users as a homogeneous group. To the
      authors' knowledge, no study has examined visit characteristics and resource
      utilization of different levels of frequent use. OBJECTIVES: 1) to determine the
      rates of ED utilization by five user groups defined by number of annual visits,
      2) to examine variations in visit characteristics by frequency of ED use, and 3)
      to compare levels of resource utilization among frequent user groups. METHODS:
      This was a retrospective, cross-sectional study of clinical and financial records
      for all ED visits to an urban, academic hospital in 2001. Multinomial logistic
      and linear regression models were used for analyses. Estimates were corrected for
      multiple comparisons (with Bonferroni corrections), where applicable, and
      adjusted for clustering within individuals (with Huber-White estimators). Outcome
      measures were triage acuity, diagnosis-related group (DRG) severity, disposition
      status, primary complaint, medical diagnosis, hospital inpatient length of stay,
      payment method, costs, and demographics. RESULTS: Patients with three to 20
      visits were more likely to be admitted to the hospital than patients visiting
      once or twice. Patients visiting more than 20 times were less likely to require
      hospital admission and more likely to present with "nonurgent" conditions, have
      lower severity scores, and elope or leave the ED without medical attention than
      patients visiting the ED once. The group had fewer inpatient days and lower
      average costs than patients visiting once. Patients with six to 20 visits had
      traditional Medicaid coverage more often than those with one or two visits.
      Virtually no patients visiting more than 20 times had Medicare or Medicaid
      managed care, a health maintenance organization, or a preferred provider
      organization. CONCLUSIONS: Frequent ED users are a heterogeneous group. Many
      patients previously thought to overutilize the ED for socioeconomic or
      insignificant medical problems are as sick as less-frequent ED users. There is a
      small subgroup with more than 20 visits who are less ill or injured but also
      incurred lower-than-average costs per visit.

PMID- 15576523
TI  - An emergency department-based nurse discharge coordinator for elder patients:
      does it make a difference?
AB  - OBJECTIVES: To evaluate the impact of an emergency department (ED)-based nurse
      discharge plan coordinator (NDPC) on unscheduled return visits within 14 days of
      discharge, satisfaction with discharge recommendations, adherence with discharge
      instructions, and perception of well-being of elder patients discharged from the
      ED. METHODS: Patients aged 75 years and older discharged from the ED of the Sir
      Mortimer B. Davis-Jewish General Hospital were recruited in a pre/post study.
      During the pre (control) phase, study patients (n = 905) received standard
      discharge care. Patients in the post (intervention) phase (n = 819) received the
      intervention of an ED-based NDPC. The intervention included patient education,
      coordination of appointments, patient education, telephone follow-up, and access
      to the NDPC for up to seven days following discharge. RESULTS: Patients in the
      two groups were similar with respect to gender and age. However, the patients
      managed by the ED NDPC appeared to be, at baseline, less autonomous, frailer, and
      sicker. The unadjusted relative risk for unscheduled return visits within 14 days
      of discharge was 0.79 (95% confidence interval [95% CI] = 0.62 to 1.02). A
      relative risk reduction of 27% (95% CI = 0% to 44%) for unscheduled return visits
      was observed for up to eight days postdischarge, and a relative risk reduction of
      19% (95% CI = -2% to 36%) for unscheduled return visits was observed for up to 14
      days postdischarge. Significant increases in satisfaction with the clarity of
      discharge information and perceived well-being were also noted. CONCLUSIONS: An
      ED-based NDPC, dedicated specifically to the discharge planning care of elder
      patients, reduces the proportion of unscheduled ED return visits and facilitates
      the transition from ED back home and into the community health care network.

PMID- 15576524
TI  - Mentoring in emergency medicine: challenges and future directions.

PMID- 15576525
TI  - Standardized reporting guidelines for studies evaluating risk stratification of
      ED patients with potential acute coronary syndromes.

PMID- 15576526
TI  - Profiles in patient safety: authority gradients in medical error.
AB  - The term "authority gradient" was first defined in aviation when it was noted
      that pilots and copilots may not communicate effectively in stressful situations
      if there is a significant difference in their experience, perceived expertise, or
      authority. A number of unintentional aviation, aerospace, and industrial
      incidents have been attributed, in part, to authority gradients. The concept of
      authority gradient was introduced to medicine in the Institute of Medicine report
      To Err Is Human, yet little has been written or acknowledged in the medical
      literature regarding its role in medical error. The practice of medicine and
      medical training programs are highly organized, hierarchical structures that
      depend on supervision by authority figures. The concept that authority gradients
      might contribute to medical error is largely unrecognized. This article presents
      one case and a series of examples to detail how authority gradients can
      contribute to medical error, and describes methods used in other disciplines to
      avoid their potentially negative impact.

PMID- 15576527
TI  - Mentoring for clinician-educators.
AB  - Mentorship has been shown to have a positive impact on academic faculty members
      in terms of career advancement. The guidance of a mentor has been shown to
      increase academic outcome measures such as peer-reviewed publications and grant
      support for junior academic faculty. In addition, career satisfaction of mentored
      faculty is greater than those with no mentorship. There is little research on the
      effects of mentorship on the careers of clinician-educators. This group has also
      been reported to have a lower scholarly productivity rate than the typical
      research-based faculty. This article addresses the current state of mentorship as
      it applies specifically to clinician-educators, offers advice on how a potential
      protege might seek out a potential mentor, and finally, suggests a possible
      mentoring system for academic emergency physicians who are focusing on careers in
      medical education.

PMID- 15576528
TI  - Mentoring medical students in academic emergency medicine.
AB  - Mentoring is an important aspect of career development for medical students,
      residents, and junior faculty. It is vital to the professional growth and
      maturation of individuals early in each phase of their careers. Additionally,
      mentoring has a critical role throughout all career stages, because the mentor
      mentee relationship provides mutual benefit to both participants. This article
      will describe the role of the mentor, suggest ways to increase the likelihood of
      successful mentoring, and identify pitfalls in the mentoring process
      predominantly related to medical students. In contrast to role models, mentors
      play an active part in the development of a young physician's career. This
      difference will be discussed. Finally, this article will describe the
      responsibilities of career guidance and recommendation letter authorship that
      mentors assume for medical students.

PMID- 15576529
TI  - Sonographic assessment of the epiglottis.
AB  - OBJECTIVES: The ideal diagnostic test for the diagnosis of epiglottitis would be
      simple, rapid, noninvasive, and highly accurate, performed at the bedside, and
      would not use ionizing radiation. The purpose of this study was to assess the
      utility of ultrasound to image the epiglottis and to determine the range of
      normal epiglottis diameter for men and women. METHODS: This was a prospective
      study of a convenience sample of 100 subjects between the ages of 18 and 50 years
      who had no known acute or chronic laryngeal diseases or surgeries. The anterior
      neck of each subject was scanned in both the long and short axis with a 5-10 MHz
      linear transducer. Sonographically, the epiglottis appeared as a curvilinear,
      hypoechoic structure with an echogenic pre-epiglottic space. The sonographic
      appearance of the epiglottis and the pre-epiglottic space were recorded and
      anteroposterior measurements of the epiglottis just distal to the hyoid bone were
      made. Comparisons between men and women were performed with use of a Student's t
      test. Pearson's correlation analysis was performed to evaluate the relationship
      between subject height and epiglottic size. RESULTS: The epiglottis was
      visualized in all 100 subjects including 62 women and 38 men. The average patient
      age was 35.2 +/- 8.1 years. The epiglottic thickness was 2.39 +/- 0.15 mm. This
      was greater in men (2.49 +/- 0.13 mm) than in women (2.34 +/- 0.13 mm) (p <
      0.001). There was moderate correlation between height and epiglottic thickness (R
      = 0.48). However, when this was analyzed separately for men and women, there was
      no significant correlation between epiglottic thickness and height. CONCLUSIONS:
      Bedside ultrasonography is easy to perform and can accurately evaluate the
      epiglottis. Further analysis should include patients with known epiglottic
      disease to assess the utility of this technique to detect pathologic enlargement.

PMID- 15576530
TI  - Emergency nurses' utilization of ultrasound guidance for placement of peripheral
      intravenous lines in difficult-access patients.
AB  - OBJECTIVES: Emergency nurses (ENs) typically place peripheral intravenous (IV)
      lines, but if repeated attempts fail, emergency physicians have to obtain
      peripheral or central access. The authors describe the patient population for
      which ultrasound (US)-guided peripheral IVs are used and evaluate the success
      rates for such lines by ENs. METHODS: This was a prospective observational study
      of ENs in a Level I trauma center with a census of 75,000, performing US-guided
      IV line placement on difficult-to-stick patients (repeated blind IV placement
      failure or established history). ENs were trained on an inanimate model after a
      45-minute lecture. Surveys were filled out after each US-guided IV attempt on a
      patient. ENs could decline to fill out surveys, which recorded the reason for use
      of US, type of patient, and success. Successful cannulation was confirmed by
      drawing blood and flushing fluids. Descriptive statistics were used to evaluated
      data. RESULTS: A total of 321 surveys were collected in a five-month period no
      ENs declined to participate. There were 280 (87%) successful attempts. Twelve
      (29%) of the 41 failure patients required central lines, 9 (22%) received
      external jugular IVs, and 20 (49%) had peripheral IV access placed under US
      guidance by another nurse or physician. Twenty-eight percent (90) of all patients
      were obese, 18% (57) had sickle cell anemia, 10% (31) were renal dialysis
      patients, 12% (40) were IV drug abusers, and 19% (61) had unspecified chronic
      illness. The remainder had no reason for difficult access given. There were four
      arterial punctures. CONCLUSIONS: ENs had a high success rate and few
      complications with use of US guidance for vascular access in a variety of
      difficult-access patients.

PMID- 15576531
TI  - The impact of the demand for clinical productivity on student teaching in
      academic emergency departments.
AB  - OBJECTIVE: Because many emergency medicine (EM) attending physicians believe the
      time demands of clinical productivity limit their ability to effectively teach
      medical students in the emergency department (ED), the purpose of this study was
      to determine if there is an inverse relationship between clinical productivity
      and teaching evaluations. METHODS: The authors conducted a prospective,
      observational, double-blind study. They asked senior medical students enrolled in
      their EM clerkship to evaluate each EM attending physician who precepted them at
      three academic EDs. After each shift, students anonymously evaluated 10
      characteristics of clinical teaching by their supervising attending physician.
      Each attending physician's clinical productivity was measured by calculating
      their total relative value units per hour (RVUs/hr) during the nine-month study
      interval. The authors compared the total RVUs/hr for each attending physician to
      the medians of their teaching evaluation scores at each ED using a Spearman rank
      correlation test. RESULTS: Seventy of 92 students returned surveys, evaluating
      580 shifts taught by 53 EM attending physicians. Each attending physician
      received an average of 11 evaluations (median score, 5 of 6) and generated a mean
      of 5.68 RVUs/hr during the study period. The correlation between evaluation
      median scores and RVUs/hr was -0.08 (p = 0.44). CONCLUSIONS: The authors found no
      statistically significant relationship between clinical productivity and teaching
      evaluations. While many EM attending physicians perceive patient care
      responsibilities to be too time consuming to allow them to be good teachers, the
      authors found that a subset of our more productive attending physicians are also
      highly rated teachers. Determining what characteristics distinguish faculty who
      are both clinically productive and highly rated teachers should help drive
      objectives for faculty development programs.

PMID- 15576532
TI  - Half-dose recombinant tissue plasminogen activator plus abciximab for stroke.

PMID- 15576533
TI  - Critical drug overdoses and emergency medical services: where should we put our
      efforts?

PMID- 15576534
TI  - Global assessment tool for emergency medicine-specific core competency
      evaluation.

PMID- 15576535
TI  - Computer-based solutions for archiving and viewing educational conferences at
      emergency medicine residency programs.

PMID- 15576536
TI  - How do people interpret their family histories of diabetes, coronary disease, or
      cancer?

PMID- 15576537
TI  - The unexpected in primary care: a multicenter study on the emergence of unvoiced
      patient agenda.
AB  - PURPOSE: Within the time constraints of a typical physician-patient encounter,
      the full patient agenda will rarely be voiced. Unexpectedly revealed issues that
      were neither on the patient's list of items for discussion nor anticipated by the
      physician constitute an emerging agenda. We aimed to quantify the occurrence rate
      of emerging agendas in primary care practices and to explain the variation
      between patients and practices. METHODS: This observational cross-sectional study
      involved 182 primary care practices in 9 European cultural regions. Consecutive
      primary care consultations were videotaped and rated. Patients completed
      preconsultation and postconsultation questionnaires assessing their expectations
      and perceived care. Emerging agenda, determined by using 11-item preconsultation
      and postconsultation questionnaires, was defined as care perceived by the patient
      to be in addition to expected care, after adjustment for cultural variations of
      patient expectations. RESULTS: For consultations involving 2,243 patients (mean
      age, 44.8 years, 58.4% women), every sixth (15.8%) consultation revealed emerging
      psychosocial agenda. Biomedical agenda emerged in 14.5% of the consultations.
      Rates for unmet expectations were 13.6% and 10.3%, respectively, for psychosocial
      and biomedical problems. Practices showed considerable heterogeneity of
      occurrence of emerging agenda (biomedical, median 13%, range 0%-67%;
      psychosocial, median 14%, range 0%-53%). After controlling for region and patient
      baseline characteristics, variables significantly related to emerging agenda were
      patient expectations and biomedical or psychosocial discourse content, but not
      consultation time or sex of the patient. A large proportion of the variance
      attributable to physicians remained concealed in a practice dummy variable
      (explaining up to 8% of the variance). CONCLUSION: Unexpected agenda emerges in
      every sixth to seventh consultation in outpatient primary care visits.

PMID- 15576538
TI  - Why we don't come: patient perceptions on no-shows.
AB  - PURPOSE: Patients who schedule clinic appointments and fail to keep them have a
      negative impact on the workflow of a clinic in many ways. This study was
      conducted to identify the reasons patients in an urban family practice setting
      give for not keeping scheduled appointments. METHODS: Semistructured interviews
      were conducted with 34 adult patients coming to the clinic for outpatient care.
      Interviews were audiotaped and transcribed verbatim. A multidisciplinary team
      used an immersion-crystallization organizing style to analyze the content of the
      qualitative interviews individually and in team meetings. RESULTS: Participants
      identified 3 types of issues related to missing appointments without notifying
      the clinic staff: emotions, perceived disrespect, and not understanding the
      scheduling system. Although they discussed logistical issues of appointment
      keeping, participants did not identify these issues as key reasons for
      nonattendance. Appointment making among these participants was driven by
      immediate symptoms and a desire for self-care. At the same time, many of these
      participants experienced anticipatory fear and anxiety about both procedures and
      bad news. Participants did not feel obligated to keep a scheduled appointment in
      part because they felt disrespected by the health care system. The effect of this
      feeling was compounded by participants' lack of understanding of the scheduling
      system. CONCLUSIONS: The results of this study suggest that reducing no-show
      rates among patients who sometimes attend might be addressed by reviewing waiting
      times and participants' perspectives of personal respect.

PMID- 15576539
TI  - Are frequent callers to family physicians high utilizers?
AB  - PURPOSE: Our objective was to describe patients who telephone frequently after
      hours to physicians (frequent callers) and categorize their medical problems and
      resource utilization. METHODS: Charts of frequent callers were reviewed and
      compared with those of a systematically selected group from the same family
      medicine residency practice (control group). Data collected included demographic
      and clinical information, as well as information on utilization of office,
      emergency department, and hospital services. In addition, 4 family physicians
      reviewed the patient information and identified the primary diagnosis for
      frequent callers. RESULTS: Frequent callers were predominately female; had 3
      times as many office visits, diagnoses, and medications; and had 8 times as many
      hospital admissions as the control group. The most common primary diagnostic
      categories were psychiatric disorders (36%), pain (21%), chronic illnesses (16%),
      pregnancy (13%), and common problems of childhood (9%). CONCLUSIONS: Frequent
      callers represent a unique group of patients with high utilization of health care
      services. Better targeted patient education and referral to other support
      services may decrease the number of calls and utilization of health services.
      Alternatively, among high utilizers, frequent telephone calls may be a substitute
      for other forms of care.

PMID- 15576540
TI  - Health care seeking among urban minority adolescent girls: the crisis at sexual
      debut.
AB  - PURPOSE: We wanted to explore the context of help seeking for reproductive and
      nonreproductive health concerns by urban adolescent girls. METHODS: We undertook
      a qualitative study using in-depth interviews of African American and Latina
      girls (n = 22) aged 13 to 19 years attending public high schools in the Bronx,
      NY. RESULTS: Before the onset of sexual activity, most girls meet health needs
      within the context of the family, relying heavily on mothers for health care and
      advice. Many new needs and concerns emerge at sexual debut. Key factors
      modulating girls' ability to address their health needs and concerns include (1)
      the strategy of selective disclosure of information perceived to be harmful to
      close family relationships or threaten privacy; (2) the desire for personalized
      care, modeled on the emotional and physical care received from mother; and (3)
      relationships with physicians that vary in quality, ranging from distant
      relationships focused on providing information to close continuity relationships.
      Core values shaping these processes include privacy, a close relationship with
      the mother, and a perception of sexual activity as dangerous. No girl was able to
      meet her specific reproductive health needs within the mother-daughter
      relationship. Some find nonmaternal sources of personalized health care and
      advice for reproductive health needs, but many do not. CONCLUSIONS: Adolescent
      girls attempt to meet reproductive health needs within a context shaped by values
      of privacy and close mother-daughter relationships. Difficulty balancing these
      values often results in inadequate support and care.

PMID- 15576541
TI  - Depression and comorbid illness in elderly primary care patients: impact on
      multiple domains of health status and well-being.
AB  - PURPOSE: Our objective was to examine the relative association of depression
      severity and chronicity, other comorbid psychiatric conditions, and coexisting
      medical illnesses with multiple domains of health status among primary care
      patients with clinical depression. METHODS: We collected cross-sectional data as
      part of a treatment effectiveness trial that was conducted in 8 diverse health
      care organizations. Patients aged 60 years and older (N = 1,801) who met
      diagnostic criteria for major depression or dysthymia participated in a baseline
      survey. A survey instrument included questions on sociodemographic
      characteristics, depression severity and chronicity, neuroticism, and the
      presence of 11 common chronic medical illnesses, as well as questions screening
      for panic disorder and posttraumatic stress disorder. Measures of 4 general
      health indicators (physical and mental component scales of the SF-12, Sheehan
      Disability Index, and global quality of life) were included. We conducted
      separate mixed-effect regression linear models predicting each of the 4 general
      health indicators. RESULTS: Depression severity was significantly associated with
      all 4 indicators of general health after controlling for sociodemographic
      differences, other psychological dysfunction, and the presence of 11 chronic
      medical conditions. Although study participants had an average of 3.8 chronic
      medical illnesses, depression severity made larger independent contributions to 3
      of the 4 general health indicators (mental functional status, disability, and
      quality of life) than the medical comorbidities. CONCLUSIONS: Recognition and
      treatment of depression has the potential to improve functioning and quality of
      life in spite of the presence of other medical comorbidities.

PMID- 15576542
TI  - Race, rural residence, and control of diabetes and hypertension.
AB  - PURPOSE: African Americans are at increased risk for diabetes mellitus and
      hypertension, and rural residents have historically had decreased access to care.
      It is unclear whether living in a rural area and being African American confers
      added risks for diagnosis and control of diabetes and hypertension. The purpose
      of this study was to examine the prevalence of diagnosed diabetes and
      hypertension, as well as control of both conditions, among rural and urban
      African Americans and whites. METHODS: We conducted an analysis of the Third
      National Health and Nutrition Examination Survey (1988-1994). Non-Hispanic
      African Americans and non-Hispanic white adults 20 years and older were
      classified according to rural or urban residence (n = 11,755). Investigated
      outcomes were previously diagnosed diabetes mellitus and hypertension and control
      of diabetes and hypertension. RESULTS: The prevalence of diagnosed diabetes was
      4.5% for urban whites, 6.5% for rural whites, 6.0% for urban African Americans,
      and 9.5% for rural African Americans. Among patients with diagnosed diabetes, 33%
      of rural whites, 43% of urban whites, 45% of urban African American, and 61% of
      rural African Americans had glycosylated hemoglobin (HbA(1c)) levels of 8% or
      higher (P < .01). Among patients with diagnosed hypertension, 11% of rural
      whites, 13% of urban whites, 20% of urban African Americans, and 23% of rural
      African Americans had diastolic blood pressure greater than 90 mmHg (P < .01). In
      regression models controlling for relevant variables, including body mass index,
      health status, access to care, education, income, and insurance, compared with
      rural African Americans, rural and urban whites were significantly more likely to
      have better glycemic control and diastolic blood pressure control. Urban African
      Americans also had better diabetes control than rural African Americans.
      CONCLUSIONS: In this nationally representative sample, rural African Americans
      are at increased risk for a lack of control of diabetes and hypertension.

PMID- 15576543
TI  - Improving test ordering in primary care: the added value of a small-group quality
      improvement strategy compared with classic feedback only.
AB  - PURPOSE: We wanted to evaluate the added value of small peer-group quality
      improvement meetings compared with simple feedback as a strategy to improve test
      ordering behavior. Numbers of tests ordered by primary care physicians are
      increasing, and many of these tests seem to be unnecessary according to
      established, evidence-based guidelines. METHODS: We enrolled 194 primary care
      physicians from 27 local primary care practice groups in 5 health care regions (5
      diagnostic centers). The study was a cluster randomized trial with randomization
      at the local physician group level. We evaluated an innovative, multifaceted
      strategy, combining written comparative feedback, group education on national
      guidelines, and social influence by peers in quality improvement sessions in
      small groups. The strategy was aimed at 3 specific clinical topics:
      cardiovascular issues, upper abdominal complaints, and lower abdominal
      complaints. The mean number of tests per physician per 6 months at baseline and
      the physicians' region were used as independent variables, and the mean number of
      tests per physician per 6 months was the dependent variable. RESULTS: The new
      strategy was executed in 13 primary care groups, whereas 14 groups received
      feedback only. For all 3 clinical topics, the decrease in mean total number of
      tests ordered by physicians in the intervention arm was far more substantial (on
      average 51 fewer tests per physician per half-year) than the decrease in mean
      number of tests ordered by physicians in the feedback arm (P = .005). Five tests
      considered to be inappropriate for the clinical problem of upper abdominal
      complaints decreased in the intervention arm, with physicians in the feedback arm
      ordering 13 more tests per 6 months (P = .002). Interdoctor variation in test
      ordering decreased more in the intervention arm. CONCLUSION: Compared with only
      disseminating comparative feedback reports to primary care physicians, the new
      strategy of involving peer interaction and social influence improved the
      physicians' test-ordering behavior. To be effective, feedback needs to be
      integrated in an interactive, educational environment.

PMID- 15576544
TI  - The biopsychosocial model 25 years later: principles, practice, and scientific
      inquiry.
AB  - The biopsychosocial model is both a philosophy of clinical care and a practical
      clinical guide. Philosophically, it is a way of understanding how suffering,
      disease, and illness are affected by multiple levels of organization, from the
      societal to the molecular. At the practical level, it is a way of understanding
      the patient's subjective experience as an essential contributor to accurate
      diagnosis, health outcomes, and humane care. In this article, we defend the
      biopsychosocial model as a necessary contribution to the scientific clinical
      method, while suggesting 3 clarifications: (1) the relationship between mental
      and physical aspects of health is complex--subjective experience depends on but
      is not reducible to laws of physiology; (2) models of circular causality must be
      tempered by linear approximations when considering treatment options; and (3)
      promoting a more participatory clinician-patient relationship is in keeping with
      current Western cultural tendencies, but may not be universally accepted. We
      propose a biopsychosocial-oriented clinical practice whose pillars include (1)
      self-awareness; (2) active cultivation of trust; (3) an emotional style
      characterized by empathic curiosity; (4) self-calibration as a way to reduce
      bias; (5) educating the emotions to assist with diagnosis and forming therapeutic
      relationships; (6) using informed intuition; and (7) communicating clinical
      evidence to foster dialogue, not just the mechanical application of protocol. In
      conclusion, the value of the biopsychosocial model has not been in the discovery
      of new scientific laws, as the term "new paradigm" would suggest, but rather in
      guiding parsimonious application of medical knowledge to the needs of each
      patient.

PMID- 15576545
TI  - Lay understanding of familial risk of common chronic diseases: a systematic
      review and synthesis of qualitative research.
AB  - PURPOSE: Although the family history is increasingly used for genetic risk
      assessment of common chronic diseases in primary care, evidence suggests that lay
      understanding about inheritance may conflict with medical models. This study
      systematically reviewed and synthesized the qualitative literature exploring
      understanding about familial risk held by persons with a family history of
      cancer, coronary artery disease, and diabetes mellitus. METHODS: Twenty-two
      qualitative articles were found after a comprehensive literature search and were
      critically appraised; 11 were included. A meta-ethnographic approach was used to
      translate the studies across each other, synthesize the translation, and express
      the synthesis. RESULTS: A dynamic process emerged by which a personal sense of
      vulnerability included some features that mirror the medical factors used to
      assess risk, such as the number of affected relatives. Other features are more
      personal, such as experience of a relative's disease, sudden or premature death,
      perceived patterns of illness relating to gender or age at death, and comparisons
      between a person and an affected relative. The developing vulnerability is
      interpreted using personal mental models, including models of disease causation,
      inheritance, and fatalism. A person's sense of vulnerability affects how that
      person copes with, and attempts to control, any perceived familial risk.
      CONCLUSIONS: Persons with a family history of a common chronic disease develop a
      personal sense of vulnerability that is informed by the salience of their family
      history and interpreted within their personal models of disease causation and
      inheritance. Features that give meaning to familial risk may be perceived
      differently by patients and professionals. This review identifies key areas for
      health professionals to explore with patients that may improve the effectiveness
      of communication about disease risk and management.

PMID- 15576547
TI  - Bag of worms.
AB  - In this story, I describe, from my perspective as a resident, working with a
      surgeon to resuscitate a woman who has suffered an avulsion of her pulmonary
      artery. The patient, a victim of a collision with an intoxicated driver, arrived
      at the hospital as I was caring for another patient who was undergoing his tenth
      admission for detoxification. Having been thrown unexpectedly into the fray, I
      looked upon a beating heart for the first time.

PMID- 15576546
TI  - Effect on health-related outcomes of interventions to alter the interaction
      between patients and practitioners: a systematic review of trials.
AB  - PURPOSE: We wanted to identify published randomized trials of interventions to
      alter the interaction between patients and practitioners, develop taxonomies of
      the interventions and outcomes, and assess the evidence that such interventions
      improve patients' health and well-being. METHODS: Undertaking a systematic review
      of randomized trials, we sought trials in primary and secondary care with health
      related outcomes, which we found by searching MEDLINE, HealthSTAR, and PsycINFO
      bibliographic databases through 1999. We also completed one round of manual
      citation searching. RESULTS: Thirty-five trials were included. Most were set in
      primary care in North America. Trials were heterogeneous in populations,
      settings, interventions, and measures. Interventions frequently combined several
      poorly described elements. Explicit theoretical underpinning was rare, and only
      one study linked intervention through process to outcome measures. Health
      outcomes were rarely measured objectively (6 of 35), and only 4 trials with
      health outcomes met predefined quality criteria. Interventions frequently altered
      the process of interactions (significantly in 73%, 22 of 30 trials). Principal
      outcomes favored the intervention group in 74% of trials (26 of 35), reaching
      statistical significance in 14 (40%). Positive effects on health outcomes
      achieved statistical significance in 44% of trials (11 of 25); negative effects
      were uncommon (5 of 25, 20%). Simple approaches to increasing the participation
      of patients in the clinical encounter, such as providing practitioners with a
      note from patients about their concerns beforehand, showed promise, as did more
      complex programs providing specific information about disease and attention to
      emotion. Apparently similar interventions varied in effectiveness across studies.
      CONCLUSIONS: Successful interactions between patients and their practitioners lie
      at the heart of medicine, yet there are few rigorous trials of well-specified
      interventions to inform best practice. Trial evidence suggests that a range of
      approaches can achieve changes in this interaction, and some show promise in
      improving patients' health. To advance knowledge further, we need to replicate
      promising studies using rigorous methods. These should include explicit
      theoretical frameworks designed to link effects on key communication and
      interaction characteristics through to effects on health outcomes.

PMID- 15576548
TI  - New models of care in family medicine.

PMID- 15576551
TI  - pH effects on the stability and dimerization of procaspase-3.
AB  - pH-dependent conformational changes are known to occur in dimeric procaspase-3,
      and they have been shown to affect the rate of automaturation. We studied the
      equilibrium unfolding of procaspase-3(C163S) as a function of pH (between pH 8.5
      and pH 4) in order to examine these changes in the context of folding and
      stability. The data show that the procaspase dimer undergoes a pH-dependent
      dissociation below pH 5, so that the protein is mostly monomeric at pH 4.
      Consistent with this, the dimer unfolds via a four-state process between pH 8.5
      and pH 4.75, in which the native dimer isomerizes to a dimeric intermediate, and
      the dimeric intermediate dissociates to a monomer, which then unfolds. In
      contrast, a small protein concentration dependence was observed by circular
      dichroism, but not by fluorescence emission, at pH 4.5 and pH 4.2. There was no
      protein-concentration dependence to the data collected at pH 4. Overall, the
      results are consistent with the redistribution of the population of native dimer
      (N(2)) to dimeric intermediate (I(2)) to monomeric intermediate (I), as the pH is
      lowered so that at pH 4, the "native" ensemble resembles the monomeric
      intermediate (I) observed during unfolding at higher pH. An emerging picture of
      the monomeric procaspase is discussed. Procaspase-3 is most stable at pH
      approximately 7 (24-26 kcal/mol), and while the stability decreased with pH, it
      was observed that dimerization contributes the majority (>70%) of the
      conformational free energy.

PMID- 15576552
TI  - Contribution of the intrinsic disulfide to the assembly mechanism of islet
      amyloid.
AB  - Amyloidogenesis from soluble protein requires conformational and oligomeric
      assembly steps. In systems where the precursor protein is natively unfolded, such
      as islet amyloid polypeptide (IAPP), forces and structural changes relevant to
      protein unfolding are not thought to participate in the assembly mechanism. Thus,
      fiber core structure elements should provide the dominant contributions to
      assembly kinetics. Here we show, however, that residues outside the amyloid core
      can influence the mechanism of IAPP fiber assembly. IAPP possesses an
      intramolecular disulfide bond between residues 2 and 7. This short-range
      disulfide prohibits the N-terminal region from adopting the beta-strand structure
      of an amyloid. We examined the role of this disulfide in fiber formation by
      generating a truncated construct (IAPP(8-37)) and a stable reduced form of the
      full-length protein (IAPP(CAM)). The fiber structures and assembly kinetics of
      these variants were assessed via optical and mass spectroscopy. Our data confirm
      that the disulfide does not contribute to the amyloid fiber core structure.
      Remarkably, however, it plays a central role in the assembly mechanism. First,
      loss of the disulfide substantially reduces fiber formation by secondary
      nucleation, i.e., the ability of pre-existing fibers to participate in the
      formation of new fibers. Second, the bypass of nucleation by seed addition is a
      two-step process, termed activation. Loss of the disulfide eliminates this two
      step nature of seeded kinetics.

PMID- 15576553
TI  - Benchmarking B cell epitope prediction: underperformance of existing methods.
AB  - Sequence profiling is used routinely to predict the location of B-cell epitopes.
      In the postgenomic era, the need for reliable epitope prediction is clear. We
      assessed 484 amino acid propensity scales in combination with ranges of plotting
      parameters to examine exhaustively the correlation of peaks and epitope location
      within 50 proteins mapped for polyclonal responses. After examining more than
      10(6) combinations, we found that even the best set of scales and parameters
      performed only marginally better than random. Our results confirm the null
      hypothesis: Single-scale amino acid propensity profiles cannot be used to predict
      epitope location reliably. The implication for studies using such methods is
      obvious.

PMID- 15576554
TI  - The length of the reactive center loop modulates the latency transition of
      plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1) belongs to the serine protease
      inhibitor (serpin) protein family, which has a common tertiary structure
      consisting of three beta-sheets and several alpha-helices. Despite the similarity
      of its structure with those of other serpins, PAI-1 is unique in its
      conformational lability, which allows the conversion of the metastable active
      form to a more stable latent conformation under physiological conditions. For the
      conformational conversion to occur, the reactive center loop (RCL) of PAI-1 must
      be mobilized and inserted into the major beta-sheet, A sheet. In an effort to
      understand how the structural conversion is regulated in this conformationally
      labile serpin, we modulated the length of the RCL of PAI-1. We show that
      releasing the constraint on the RCL by extension of the loop facilitates a
      conformational transition of PAI-1 to a stable state. Biochemical data strongly
      suggest that the stabilization of the transformed conformation is owing to the
      insertion of the RCL into A beta-sheet, as in the known latent form. In contrast,
      reducing the loop length drastically retards the conformational change. The
      results clearly show that the constraint on the RCL is a factor that regulates
      the conformational transition of PAI-1.

PMID- 15576555
TI  - Crystal structure of the histidine-containing phosphotransfer protein ZmHP2 from
      maize.
AB  - In higher plants, histidine-aspartate phosphorelays (two-component system) are
      involved in hormone signaling and stress responses. In these systems, histidine
      containing phosphotransfer (HPt) proteins mediate the signal transmission from
      sensory histidine kinases to response regulators, including integration of
      several signaling pathways or branching into different pathways. We have
      determined the crystal structure of a maize HPt protein, ZmHP2, at 2.2 A
      resolution. ZmHP2 has six alpha-helices with a four-helix bundle at the C
      terminus, a feature commonly found in HPt domains. In ZmHP2, almost all of the
      conserved residues among plant HPt proteins surround this histidine, probably
      forming the docking interface for the receiver domain of histidine kinase or the
      response regulator. Arg102 of ZmHP2 is conserved as a basic residue in plant HPt
      proteins. In bacteria, it is replaced by glutamine or glutamate that form a
      hydrogen bond to Ndelta atoms of the phospho-accepting histidine. It may play a
      key role in the complex formation of ZmHP2 with receiver domains.

PMID- 15576556
TI  - Ser95, Asn97, and Thr78 are important for the catalytic function of porcine NADP
      dependent isocitrate dehydrogenase.
AB  - The mammalian mitochondrial NADP-dependent isocitrate dehydrogenase is a citric
      acid cycle enzyme and an important contributor to cellular defense against
      oxidative stress. The Mn(2+)-isocitrate complex of the porcine enzyme was
      recently crystallized; its structure indicates that Ser(95), Asn(97), and Thr(78)
      are within hydrogen-bonding distance of the gamma-carboxylate of enzyme-bound
      isocitrate. We used site-directed mutagenesis to replace each of these residues
      by Ala and Asp. The wild-type and mutant enzymes were expressed in Escherichia
      coli and purified to homogeneity. All the enzymes retain their native dimeric
      structures and secondary structures as monitored by native gel electrophoresis
      and circular dichroism, respectively. V(max) of the three alanine mutants is
      decreased to 24%-38% that of wild-type enzyme, with further decreases in the
      aspartate mutants. For T78A and S95A mutants, the major changes are the 10- to
      100-fold increase in the K(m) values for isocitrate and Mn(2+). The results
      suggest that Thr(78) and Ser(95) function to strengthen the enzyme's affinity for
      Mn(2+)-isocitrate by hydrogen bonding to the gamma-carboxylate of isocitrate. For
      the Asn(97) mutants, the K(m) values are much less affected. The major change in
      the N97A mutant is the increase in pK(a) of the ionizable metal-liganded hydroxyl
      of enzyme-bound isocitrate from 5.23 in wild type to 6.23 in the mutant enzyme.
      The hydrogen bond between Asn(97) and the gamma-carboxylate of isocitrate may
      position the substrate to promote a favorable lowering of the pK of the enzyme
      isocitrate complex. Thus, Thr(78), Ser(95), and Asn(97) perform important but
      distinguishable roles in catalysis by porcine NADP-specific isocitrate
      dehydrogenase.

PMID- 15576557
TI  - Solution structure of the rhodanese homology domain At4g01050(175-295) from
      Arabidopsis thaliana.
AB  - The three-dimensional structure of the rhodanese homology domain At4g01050(175
      195) from Arabidopsis thaliana has been determined by solution nuclear magnetic
      resonance methods based on 3043 upper distance limits derived from NOE
      intensities measured in three-dimensional NOESY spectra. The structure shows a
      backbone root mean square deviation to the mean coordinates of 0.43 A for the
      structured residues 7-125. The fold consists of a central parallel beta-sheet
      with five strands in the order 1-5-4-2-3 and arranged in the conventional
      counterclockwise twist, and helices packing against each side of the beta-sheet.
      Comparison with the sequences of other proteins with a rhodanese homology domain
      in Arabidopsis thaliana indicated residues that could play an important role in
      the scaffold of the rhodanese homology domain. Finally, a three-dimensional
      structure comparison of the present noncatalytic rhodanese homology domain with
      the noncatalytic rhodanese domains of sulfurtransferases from other organisms
      discloses differences in the length and conformation of loops that could throw
      light on the role of the noncatalytic rhodanese domain in sulfurtransferases.

PMID- 15576558
TI  - Direct demonstration of carbamoyl phosphate formation on the C-terminal domain of
      carbamoyl phosphate synthetase.
AB  - Carbamoyl phosphate synthetase synchronizes the utilization of two ATP molecules
      at duplicated ATP-grasp folds to catalyze carbamoyl phosphate formation. To
      define the dedicated functional role played by each of the two ATP sites, we have
      carried out pulse/labeling studies using the synthetases from Aquifex aeolicus
      and Methanococcus jannaschii, hyperthermophilic organisms that encode the two ATP
      grasp folds on separate subunits. These studies allowed us to differentially
      label each active site with [gamma-(32)P]ATP and determine the fate of the
      labeled gamma-phosphate in the synthetase reaction. Our results provide the first
      direct demonstration that enzyme-catalyzed transfer of phosphate from ATP to
      carbamate occurs on the more C-terminal of the two ATP-grasp folds. These
      findings rule out one mechanism proposed for carbamoyl phosphate synthetase,
      where one ATP acts as a molecular switch, and provide additional support for a
      sequential reaction mechanism where the gamma-phosphate groups of both ATP
      molecules are transferred to reactants. CP synthesis by subunit C in our single
      turnover pulse/chase assays did not require subunit N, but subunit N was required
      for detectable CP synthesis in the traditional continuous assay. These findings
      suggest that cross-talk between domain N and C is required for product release
      from subunit C.

PMID- 15576559
TI  - A novel method reveals that solvent water favors polyproline II over beta-strand
      conformation in peptides and unfolded proteins: conditional hydrophobic
      accessible surface area (CHASA).
AB  - In aqueous solution, the ensemble of conformations sampled by peptides and
      unfolded proteins is largely determined by their interaction with water. It has
      been a long-standing goal to capture these solute-water energetics accurately and
      efficiently in calculations. Historically, accessible surface area (ASA) has been
      used to estimate these energies, but this method breaks down when applied to
      amphipathic peptides and proteins. Here we introduce a novel method in which
      hydrophobic ASA is determined after first positioning water oxygens in hydrogen
      bonded orientations proximate to all accessible peptide/protein backbone N and O
      atoms. This conditional hydrophobic accessible surface area is termed CHASA. The
      CHASA method was validated by predicting the polyproline-II (P(II)) and beta
      strand conformational preferences of non-proline residues in the coil library
      (i.e., non-alpha-helix, non-beta-strand, non-beta-turn library derived from X-ray
      elucidated structures). Further, the method successfully rationalizes the
      previously unexplained solvation energies in polyalanyl peptides and compares
      favorably with published experimentally determined P(II) residue propensities. We
      dedicate this paper to Frederic M. Richards.

PMID- 15576560
TI  - Modifications of human betaA1/betaA3-crystallins include S-methylation,
      glutathiolation, and truncation.
AB  - Disulfide bonding of lens crystallins contributes to the aggregation and
      insolubilization of these proteins that leads to cataract. A high concentration
      of reduced glutathione is believed to be key in preventing oxidation of
      crystallin sulfhydryls to form disulfide bonds. This protective role is decreased
      in aged lenses because of lower glutathione levels, especially in the nucleus. We
      recently found that human gamma-crystallins undergo S-methylation at exposed
      cysteine residues, a reaction that may prevent disulfide bonding. We report here
      that betaA1/A3-crystallins are also methylated at specific cysteine residues and
      are the most heavily methylated of the human lens crystallins. Among the
      methylated sites, Cys 64, Cys 99, and Cys 167 of betaA1-crystallin, methylation
      at Cys 99 is highest. Cys 64 and Cys 99 are also glutathiolated, even in a
      newborn lens. These post-translational modifications of the exposed cysteines may
      be important for maintaining the crystallin structure required for lens
      transparency. Previously unreported N-terminal truncations were also found.

PMID- 15576561
TI  - Amyloid accomplices and enforcers.
AB  - Amyloid-related diseases are often ascribed to protein "misfolding." Yet in the
      absence of high-resolution structures for mature fibrils or intermediates, the
      connection between the mechanism of amyloid formation and protein folding remains
      tenuous. The simplistic view of amyloid fibrillogenesis as a homogeneous self
      assembly process is being increasingly challenged by observations that amyloids
      interact with a variety of cofactors including metals, glycosaminoglycans,
      glycoproteins such as serum amyloid P and apolipo-protein E, and constituents of
      basement membranes such as perlecan, laminin, and agrin. These "pathological
      chaperones" have effects that range from mediating the rate of amyloid fibril
      formation to increasing the stability of amyloid deposits, and may contribute to
      amyloid toxicity. An increasing appreciation of the role of accessory molecules
      in amyloid etiology has paved the way to novel diagnostics and therapeutic
      strategies.

PMID- 15576562
TI  - Identifying natural substrates for chaperonins using a sequence-based approach.
AB  - The Escherichia coli chaperonin machinery, GroEL, assists the folding of a number
      of proteins. We describe a sequence-based approach to identify the natural
      substrate proteins (SPs) for GroEL. Our method is based on the hypothesis that
      natural SPs are those that contain patterns of residues similar to those found in
      either GroES mobile loop and/or strongly binding peptide in complex with GroEL.
      The method is validated by comparing the predicted results with experimentally
      determined natural SPs for GroEL. We have searched for such patterns in five
      genomes. In the E. coli genome, we identify 1422 (about one-third) sequences that
      are putative natural SPs. In Saccharomyces cerevisiae, 2885 (32%) of sequences
      can be natural substrates for Hsp60, which is the analog of GroEL. The precise
      number of natural SPs is shown to be a function of the number of contacts an SP
      makes with the apical domain (N(C)) and the number of binding sites (N(B)) in the
      oligomer with which it interacts. For known SPs for GroEL, we find approximately
      4 < N(C) < 5 and 2 <or= N(B) <or= 4. A limited analysis of the predicted binding
      sequences shows that they do not adopt any preferred secondary structure. Our
      method also predicts the putative binding regions in the identified SPs. The
      results of our study show that a variety of SPs, associated with diverse
      functions, can interact with GroEL.

PMID- 15576563
TI  - Structure of rhodocetin reveals noncovalently bound heterodimer interface.
AB  - Rhodocetin is a unique heterodimer consisting of alpha- and beta-subunits of 133
      and 129 residues, respectively. The molecule, purified from the crude venom of
      the Malayan pit viper, Calloselasma rhodostoma, functions as an inhibitor of
      collagen-induced aggregation. Rhodocetin has been shown to have activity only
      when present as a dimer. The dimer is formed without an intersubunit disulfide
      bridge, unlike all the other Ca(2+)-dependent lectin-like proteins. We report
      here the 1.9 A resolution structure of rhodocetin, which reveals the compensatory
      interactions that occur in the absence of the disulfide bridge to preserve
      activity.

PMID- 15576564
TI  - A computational method for the analysis and prediction of protein:phosphopeptide
      binding sites.
AB  - Phosphopeptide-binding domains, including the FHA, SH2, WW, WD40, MH2, and Polo
      box domains, as well as the 14-3-3 proteins, exert control functions in important
      processes such as cell growth, division, differentiation, and apoptosis.
      Structures and mechanisms of phosphopeptide binding are generally diverse,
      revealing few general principles. A computational method for analysis of
      phosphopeptide-binding domains was therefore developed to elucidate the physical
      and chemical nature of phosphopeptide binding, given this lack of structural
      similarity. The surfaces of nine phosphopeptide-binding proteins, representing
      seven distinct classes of phosphopeptide-binding modules, were discretized, and
      encoded with information about amino acid identity, surface curvature, and
      electrostatic potential at every point on the surface in order to identify local
      surface properties enriched in phosphoresidue contact sites. Cross-validation
      indicated that propensities corresponding to this enrichment calculated from a
      subset of the training data could be used to predict the phosphoresidue contact
      site on proteins not used in training with no false negative results, and with
      few unconfirmed positive predictions. The locations of phosphoresidue contact
      sites were then predicted on the surfaces of the checkpoint kinase Chk1 and the
      BRCA1 BRCT repeat domain, and these predictions are consistent with recent
      experimental evidence.

PMID- 15576565
TI  - Orthogonal site-specific protein modification by engineering reversible thiol
      protection mechanisms.
AB  - Covalent modification is an important strategy for introducing new functions into
      proteins. As engineered proteins become more sophisticated, it is often desirable
      to introduce multiple, modifications involving several different functionalities
      in a site-specific manner. Such orthogonal labeling schemes require independent
      labeling of differentially reactive nucleophilic amino acid side chains. We have
      developed two protein-mediated protection schemes that permit independent
      labeling of multiple thiols. These schemes exploit metal coordination or
      disulfide bond formation to reversibly protect cysteines in a Cys(2)His(2) zinc
      finger domain. We constructed a variety of N- and C-terminal fusions of these
      domains with maltose-binding protein, which were labeled with two or three
      different fluorophores. Multiple modifications were made by reacting an
      unprotected cysteine in MBP first, deprotecting the zinc finger, and then
      reacting the zinc finger cysteines. The fusion proteins were orthogonally labeled
      with two different fluorophores, which exhibited intramolecular fluorescene
      resonance energy transfer (FRET). These conjugates showed up to a threefold
      ratiometric change in emission intensities in response to maltose binding. We
      also demonstrated that the metal- and redox-mediated protection methods can be
      combined to produce triple independent modifications, and prepared a protein
      labeled with three different fluorophores that exhibited a FRET relay. Finally,
      labeled glucose-binding protein was covalently patterned on glass slides using
      thiol-mediated immobilization chemistries. Together, these experiments
      demonstrated that reversible thiol protection schemes provide a rapid,
      straightforward method for producing multiple, site-specific modifications.

PMID- 15576566
TI  - Computational analysis of the transient movement of helices in sensory rhodopsin
      II.
AB  - MD simulation of sensory rhodopsin II was executed for three intermediates
      (ground-state, K-state, M-state) appearing in its photocycle. We observed a large
      displacement of the cytoplasmic side of helixF only in M-state among the three
      intermediates. This displacement was transmitted to TM2, and the cytoplasmic side
      of TM2 rotated clockwise. These transient movements are in agreement with the
      results of an EPR experiment. That is, the early stage of signal transduction in
      a sRII-HtrII complex was successfully reproduced by the in silico MD simulation.
      By analyzing the structure of the sRII-HtrII complex, the following findings
      about the photocycle of sRII were obtained: (1) The hydrogen bonds between helixF
      and other helices determine the direction of the movement of helixF; (2) three
      amino acids (Arg162, Thr189, Tyr199) are essential for sRII-HtrII binding and
      contribute to the motion transfer from sRII to HtrII; (3) after the isomerization
      of retinal, a major conformational change of retinal was caused by proton
      transfer from Schiff base to Asp75, which, in turn, triggers the steric collision
      of retinal with Trp171. This is the main reason for the movement of the
      cytoplasmic side of helixF.

PMID- 15576567
TI  - A comparative study of the alpha-subdomains of bovine and human alpha-lactalbumin
      reveals key differences that correlate with molten globule stability.
AB  - The alpha-lactalbumins form stable molten globule states under a range of
      conditions, with the low pH form being the best characterized. The stability of
      the molten globule varies among different members of this family, but the origin
      of the stability difference is not clear. We compare the folding and stability of
      alpha-subdomain constructs of human and bovine alpha-lactalbumin. Previous
      studies have demonstrated that the isolated alpha-subdomain of human alpha
      lactalbumin folds and forms a molten globule state. The minimum core construct
      has been defined to include the A, B, and D alpha-helices and the C-terminal
      3(10) helix. A construct corresponding to the same region of bovine alpha
      lactalbumin is much less structured and less stable than the human alpha
      lactalbumin construct. Addition of the C-helix to generate a 75-residue bovine
      construct does not lead to a significant increase in structure or stability. This
      construct (AB-CD/3(10)) contains the entire alpha-subdomain of bovine alpha
      lactalbumin. Thus molten globule formation in the human protein, but not in the
      bovine protein, can be rationalized on the basis of a stable alpha-subdomain.
      Interactions involving more of the protein chain are required to generate a well
      structured molten globule in the bovine protein. Comparison of AB-CD/3(10) to the
      molten globule formed by the intact protein and to the protein with the 6-120
      disulfide reduced indicates that both the beta-subdomain and the 6-120 disulfide
      play a role in stabilizing the bovine alpha-lactalbumin molten globule.

PMID- 15576568
TI  - Electric charge balance mechanism of extended soluble proteins.
AB  - Extended proteins such as calmodulin and troponin C have two globular terminal
      domains linked by a central region that is exposed to water and often acts as a
      function-regulating element. The mechanisms that stabilize the tertiary structure
      of extended proteins appear to differ greatly from those of globular proteins.
      Identifying such differences in physical properties of amino acid sequences
      between extended proteins and globular proteins can provide clues useful for
      identification of extended proteins from complete genomes including orphan
      sequences. In the present study, we examined the structure and amino acid
      sequence of extended proteins. We found that extended proteins have a large net
      electric charge, high charge density, and an even balance of charge between the
      terminal domains, indicating that electrostatic interaction is a dominant factor
      in stabilization of extended proteins. Additionally, the central domain exposed
      to water contained many amphiphilic residues. Extended proteins can be identified
      from these physical properties of the tertiary structure, which can be deduced
      from the amino acid sequence. Analysis of physical properties of amino acid
      sequences can provide clues to the mechanism of protein folding. Also, structural
      changes in extended proteins may be caused by formation of molecular complexes.
      Long-range effects of electrostatic interactions also appear to play important
      roles in structural changes of extended proteins.

PMID- 15576569
TI  - Hydrogen exchange and ligand binding: ligand-dependent and ligand-independent
      protection in the Src SH3 domain.
AB  - Amide hydrogen-deuterium exchange has proven to be a powerful tool for detecting
      and characterizing high-energy conformations in protein ensembles. Since
      interactions with ligands can modulate these high-energy conformations, hydrogen
      exchange appears to be an ideal experimental probe of the physical mechanisms
      underlying processes like allosteric regulation. The chemical mechanism of
      hydrogen exchange, however, can complicate such studies. Here, we examine
      hydrogen exchange rates in a simple model system, the c-Src SH3 domain
      interacting with a short peptide ligand. Addition of ligand slows the rates of
      hydrogen exchange at nearly every amide for which we can obtain data. Careful
      analysis, however, reveals that this slowing is due primarily to a reduction in
      the population of free protein in the system, and not to any specific property of
      the complex. We present a method to separate the contributions of free and bound
      protein to the exchange kinetics that has allowed us to identify the subset of
      amides where exchange arises directly from the complex. These results demonstrate
      that the slowing of hydrogen exchange induced by ligand interactions should be
      interpreted with caution, and more extensive experiments are required to
      correlate changes in hydrogen exchange with changes in structure or internal
      dynamics.

PMID- 15576571
TI  - Escape of intracellular Shigella from autophagy.
AB  - The degradation of undesirable cellular components or organelles, including
      invading microbes, by autophagy is crucial for cell survival. Here, Shigella, an
      invasive bacteria, was found to be able to escape autophagy by secreting IcsB by
      means of the type III secretion system. Mutant bacteria lacking IcsB were trapped
      by autophagy during multiplication within the host cells. IcsB did not directly
      inhibit autophagy. Rather, Shigella VirG, a protein required for intracellular
      actin-based motility, induced autophagy by binding to the autophagy protein,
      Atg5. In nonmutant Shigella, this binding is competitively inhibited by IcsB
      binding to VirG.

PMID- 15576572
TI  - Asynchronous terrestrial and marine signals of climate change during Heinrich
      events.
AB  - Tropical regions have been reported to play a key role in climate dynamics. To
      date, however, there are uncertainties in the timing and the amplitude of the
      response of tropical ecosystems to millennial-scale climate change. We present
      evidence of an asynchrony between terrestrial and marine signals of climate
      change during Heinrich events preserved in marine sediment cores from the
      Brazilian continental margin. The inferred time lag of about 1000 to 2000 years
      is much larger than the ecological response to recent climate change and appears
      to be related to the nature of hydrological changes.

PMID- 15576573
TI  - The duration of forest stages in southern Europe and interglacial climate
      variability.
AB  - Foraminiferal oxygen isotope and pollen analyses from a deep-sea sequence off
      southwest Portugal show that the duration of temperate stages on land over the
      past 350,000 years varied considerably. The record shows forest contractions
      during intervals of low ice volume, coeval with declines in atmospheric methane,
      after which tree populations did not always recover. What emerges is that,
      although the broad timing of interglacials is consistent with orbital theory,
      their specific duration may be dictated by millennial variability. This
      complicates the prediction of the natural duration of interglacials, at least
      until the origin of this climate variability is understood.

PMID- 15576574
TI  - Clinical trials and public trust.

PMID- 15576575
TI  - U.S. science budget. Science agencies caught in postelection spending squeeze.

PMID- 15576576
TI  - The omnibus bill isn't only about dollars.

PMID- 15576578
TI  - Lunar exploration. India, China vie for best look at the moon.

PMID- 15576577
TI  - Toxicology. Factory study shows low levels of benzene reduce blood cell counts.

PMID- 15576579
TI  - Cell biology. Long-term stress may chip away at the ends of chromosomes.

PMID- 15576581
TI  - ITER. Cadarache: more than just a candidate site.

PMID- 15576580
TI  - Genetic diversity. Consortium hopes to map human history in Asia.

PMID- 15576582
TI  - Science policy. Europe advances a plan for merit-based funding.

PMID- 15576583
TI  - Revisiting the Bhopal tragedy.

PMID- 15576584
TI  - Agriculture. Plant pathologists gear up for battle with dread fungus.

PMID- 15576585
TI  - Clinical trials. Nail-biting time for trials of COX-2 drugs.

PMID- 15576586
TI  - Division for Planetary Sciences meeting. Did Jupiter and Saturn team up to pummel
      the inner solar system?

PMID- 15576587
TI  - Division for Planetary Sciences meeting. Hydrocarbon seas of Titan gone missing.

PMID- 15576588
TI  - Division for Planetary Sciences meeting. Amazing shrinking Kuiper belt objects.

PMID- 15576589
TI  - Division for Planetary Sciences meeting. Snapshots from the meeting.

PMID- 15576590
TI  - Prescribed fire and natural disturbance.

PMID- 15576591
TI  - The origins of Afroasiatic.

PMID- 15576592
TI  - Earth's entropy.

PMID- 15576593
TI  - The brain, neurons, and behavior.

PMID- 15576594
TI  - Beyond the ivory tower. The scientific consensus on climate change.

PMID- 15576595
TI  - Immunology. The elusive NKT cell antigen--is the search over?

PMID- 15576596
TI  - Planetary science. Proof for water, hints of life?

PMID- 15576597
TI  - Applied physics. X-ray movies of wiggling crystals.

PMID- 15576598
TI  - Biomedicine. Prion dormancy and disease.

PMID- 15576599
TI  - Developmental biology. Bits and pieces.

PMID- 15576600
TI  - Evolution. Sex...only if really necessary in a feminine monarchy.

PMID- 15576602
TI  - The Opportunity Rover's Athena science investigation at Meridiani Planum, Mars.
AB  - The Mars Exploration Rover Opportunity has investigated the landing site in Eagle
      crater and the nearby plains within Meridiani Planum. The soils consist of fine
      grained basaltic sand and a surface lag of hematite-rich spherules, spherule
      fragments, and other granules. Wind ripples are common. Underlying the thin soil
      layer, and exposed within small impact craters and troughs, are flat-lying
      sedimentary rocks. These rocks are finely laminated, are rich in sulfur, and
      contain abundant sulfate salts. Small-scale cross-lamination in some locations
      provides evidence for deposition in flowing liquid water. We interpret the rocks
      to be a mixture of chemical and siliciclastic sediments formed by episodic
      inundation by shallow surface water, followed by evaporation, exposure, and
      desiccation. Hematite-rich spherules are embedded in the rock and eroding from
      them. We interpret these spherules to be concretions formed by postdepositional
      diagenesis, again involving liquid water.

PMID- 15576603
TI  - Pancam multispectral imaging results from the Opportunity Rover at Meridiani
      Planum.
AB  - Panoramic Camera (Pancam) images from Meridiani Planum reveal a low-albedo,
      generally flat, and relatively rock-free surface. Within and around impact
      craters and fractures, laminated outcrop rocks with higher albedo are observed.
      Fine-grained materials include dark sand, bright ferric iron-rich dust, angular
      rock clasts, and millimeter-size spheroidal granules that are eroding out of the
      laminated rocks. Spectra of sand, clasts, and one dark plains rock are consistent
      with mafic silicates such as pyroxene and olivine. Spectra of both the spherules
      and the laminated outcrop materials indicate the presence of crystalline ferric
      oxides or oxyhydroxides. Atmospheric observations show a steady decline in dust
      opacity during the mission. Astronomical observations captured solar transits by
      Phobos and Deimos and time-lapse observations of sunsets.

PMID- 15576604
TI  - In situ evidence for an ancient aqueous environment at Meridiani Planum, Mars.
AB  - Sedimentary rocks at Eagle crater in Meridiani Planum are composed of fine
      grained siliciclastic materials derived from weathering of basaltic rocks,
      sulfate minerals (including magnesium sulfate and jarosite) that constitute
      several tens of percent of the rock by weight, and hematite. Cross-stratification
      observed in rock outcrops indicates eolian and aqueous transport. Diagenetic
      features include hematite-rich concretions and crystal-mold vugs. We interpret
      the rocks to be a mixture of chemical and siliciclastic sediments with a complex
      diagenetic history. The environmental conditions that they record include
      episodic inundation by shallow surface water, evaporation, and desiccation. The
      geologic record at Meridiani Planum suggests that conditions were suitable for
      biological activity for a period of time in martian history.

PMID- 15576605
TI  - Opportunity at Meridiani Planum: plates.

PMID- 15576606
TI  - Soils of Eagle crater and Meridiani Planum at the Opportunity Rover landing site.
AB  - The soils at the Opportunity site are fine-grained basaltic sands mixed with dust
      and sulfate-rich outcrop debris. Hematite is concentrated in spherules eroded
      from the strata. Ongoing saltation exhumes the spherules and their fragments,
      concentrating them at the surface. Spherules emerge from soils coated, perhaps
      from subsurface cementation, by salts. Two types of vesicular clasts may
      represent basaltic sand sources. Eolian ripples, armored by well-sorted hematite
      rich grains, pervade Meridiani Planum. The thickness of the soil on the plain is
      estimated to be about a meter. The flatness and thin cover suggest that the plain
      may represent the original sedimentary surface.

PMID- 15576607
TI  - Evidence from Opportunity's Microscopic Imager for water on Meridiani Planum.
AB  - The Microscopic Imager on the Opportunity rover analyzed textures of soils and
      rocks at Meridiani Planum at a scale of 31 micrometers per pixel. The uppermost
      millimeter of some soils is weakly cemented, whereas other soils show little
      evidence of cohesion. Rock outcrops are laminated on a millimeter scale; image
      mosaics of cross-stratification suggest that some sediments were deposited by
      flowing water. Vugs in some outcrop faces are probably molds formed by
      dissolution of relatively soluble minerals during diagenesis. Microscopic images
      support the hypothesis that hematite-rich spherules observed in outcrops and
      soils also formed diagenetically as concretions.

PMID- 15576608
TI  - Localization and physical property experiments conducted by Opportunity at
      Meridiani Planum.
AB  - The location of the Opportunity landing site was determined to better than 10-m
      absolute accuracy from analyses of radio tracking data. We determined Rover
      locations during traverses with an error as small as several centimeters using
      engineering telemetry and overlapping images. Topographic profiles generated from
      rover data show that the plains are very smooth from meter- to centimeter-length
      scales, consistent with analyses of orbital observations. Solar cell output
      decreased because of the deposition of airborne dust on the panels. The lack of
      dust-covered surfaces on Meridiani Planum indicates that high velocity winds must
      remove this material on a continuing basis. The low mechanical strength of the
      evaporitic rocks as determined from grinding experiments, and the abundance of
      coarse-grained surface particles argue for differential erosion of Meridiani
      Planum.

PMID- 15576609
TI  - Mineralogy at Meridiani Planum from the Mini-TES Experiment on the Opportunity
      Rover.
AB  - The Miniature Thermal Emission Spectrometer (Mini-TES) on Opportunity
      investigated the mineral abundances and compositions of outcrops, rocks, and
      soils at Meridiani Planum. Coarse crystalline hematite and olivine-rich basaltic
      sands were observed as predicted from orbital TES spectroscopy. Outcrops of
      aqueous origin are composed of 15 to 35% by volume magnesium and calcium sulfates
      [a high-silica component modeled as a combination of glass, feldspar, and sheet
      silicates (approximately 20 to 30%)], and hematite; only minor jarosite is
      identified in Mini-TES spectra. Mini-TES spectra show only a hematite signature
      in the millimeter-sized spherules. Basaltic materials have more plagioclase than
      pyroxene, contain olivine, and are similar in inferred mineral composition to
      basalt mapped from orbit. Bounce rock is dominated by clinopyroxene and is close
      in inferred mineral composition to the basaltic martian meteorites. Bright wind
      streak material matches global dust. Waterlain rocks covered by unaltered
      basaltic sands suggest a change from an aqueous environment to one dominated by
      physical weathering.

PMID- 15576610
TI  - Jarosite and hematite at Meridiani Planum from Opportunity's Mossbauer
      Spectrometer.
AB  - Mossbauer spectra measured by the Opportunity rover revealed four mineralogical
      components in Meridiani Planum at Eagle crater: jarosite- and hematite-rich
      outcrop, hematite-rich soil, olivine-bearing basaltic soil, and a pyroxene
      bearing basaltic rock (Bounce rock). Spherules, interpreted to be concretions,
      are hematite-rich and dispersed throughout the outcrop. Hematitic soils both
      within and outside Eagle crater are dominated by spherules and their fragments.
      Olivine-bearing basaltic soil is present throughout the region. Bounce rock is
      probably an impact erratic. Because jarosite is a hydroxide sulfate mineral, its
      presence at Meridiani Planum is mineralogical evidence for aqueous processes on
      Mars, probably under acid-sulfate conditions.

PMID- 15576611
TI  - Chemistry of rocks and soils at Meridiani Planum from the Alpha Particle X-ray
      Spectrometer.
AB  - The Alpha Particle X-ray Spectrometer on the Opportunity rover determined major
      and minor elements of soils and rocks in Meridiani Planum. Chemical compositions
      differentiate between basaltic rocks, evaporite-rich rocks, basaltic soils, and
      hematite-rich soils. Although soils are compositionally similar to those at
      previous landing sites, differences in iron and some minor element concentrations
      signify the addition of local components. Rocky outcrops are rich in sulfur and
      variably enriched in bromine relative to chlorine. The interaction with water in
      the past is indicated by the chemical features in rocks and soils at this site.

PMID- 15576612
TI  - First Atmospheric Science Results from the Mars Exploration Rovers Mini-TES.
AB  - Thermal infrared spectra of the martian atmosphere taken by the Miniature Thermal
      Emission Spectrometer (Mini-TES) were used to determine the atmospheric
      temperatures in the planetary boundary layer and the column-integrated optical
      depth of aerosols. Mini-TES observations show the diurnal variation of the
      martian boundary layer thermal structure, including a near-surface superadiabatic
      layer during the afternoon and an inversion layer at night. Upward-looking Mini
      TES observations show warm and cool parcels of air moving through the Mini-TES
      field of view on a time scale of 30 seconds. The retrieved dust optical depth
      shows a downward trend at both sites.

PMID- 15576613
TI  - Atmospheric imaging results from the Mars exploration rovers: Spirit and
      Opportunity.
AB  - A visible atmospheric optical depth of 0.9 was measured by the Spirit rover at
      Gusev crater and by the Opportunity rover at Meridiani Planum. Optical depth
      decreased by about 0.6 to 0.7% per sol through both 90-sol primary missions. The
      vertical distribution of atmospheric dust at Gusev crater was consistent with
      uniform mixing, with a measured scale height of 11.56 +/- 0.62 kilometers. The
      dust's cross section weighted mean radius was 1.47 +/- 0.21 micrometers (mm) at
      Gusev and 1.52 +/- 0.18 mm at Meridiani. Comparison of visible optical depths
      with 9-mm optical depths shows a visible-to-infrared optical depth ratio of 2.0
      +/- 0.2 for comparison with previous monitoring of infrared optical depths.

PMID- 15576614
TI  - The cryptic filtering house of an invertebrate larva.
AB  - Planktonic larvae of the annelid Pectinaria californiensis construct and inhabit
      cryptic houses through which they filter seawater to concentrate food. Although
      filtering houses may be unique to pectinariid larvae, other transparent and
      ephemeral structures are secreted by the larvae of many marine invertebrates and
      may be involved in the performance of a variety of critical larval functions.

PMID- 15576615
TI  - Abrupt temperature changes in the Western Mediterranean over the past 250,000
      years.
AB  - A continuous high-resolution Western Mediterranean sea surface temperature (SST)
      alkenone record spanning the past 250,000 years shows that abrupt changes were
      more common at warming than at cooling. During marine isotope stage (MIS) 6, SST
      oscillated following a stadial-interstadial pattern but at lower intensities and
      rates of change than in the Dansgaard/Oeschger events of MIS 3. Some of the most
      prominent events occurred over MISs 5 and 7, after prolonged warm periods of high
      stability. Climate during the whole period was predominantly maintained in
      interglacial-interstadial conditions, whereas the duration of stadials was much
      shorter.

PMID- 15576616
TI  - Efficient deactivation of a model base pair via excited-state hydrogen transfer.
AB  - We present experimental and theoretical evidence for an excited-state
      deactivation mechanism specific to hydrogen-bonded aromatic dimers, which may
      account, in part, for the photostability of the Watson-Crick base pairs in DNA.
      Femtosecond time-resolved mass spectroscopy of 2-aminopyridine clusters reveals
      an excited-state lifetime of 65 +/- 10 picoseconds for the near-planar hydrogen
      bonded dimer, which is significantly shorter than the lifetime of either the
      monomer or the 3- and 4-membered nonplanar clusters. Ab initio calculations of
      reaction pathways and potential-energy profiles identify the mechanism of the
      enhanced excited-state decay of the dimer: Conical intersections connect the
      locally excited 1pipi* state and the electronic ground state with a 1pipi* charge
      transfer state that is strongly stabilized by the transfer of a proton.

PMID- 15576617
TI  - Interface structure and atomic bonding characteristics in silicon nitride
      ceramics.
AB  - Direct atomic resolution images have been obtained that illustrate how a range of
      rare-earth atoms bond to the interface between the intergranular phase and the
      matrix grains in an advanced silicon nitride ceramic. It has been found that each
      rare-earth atom bonds to the interface at a different location, depending on atom
      size, electronic configuration, and the presence of oxygen at the interface. This
      is the key factor to understanding the origin of the mechanical properties in
      these ceramics and will enable precise tailoring in the future to critically
      improve the materials' performance in wide-ranging applications.

PMID- 15576618
TI  - Coherent atomic motions in a nanostructure studied by femtosecond X-ray
      diffraction.
AB  - Reversible structural changes of a nanostructure were measured nondestructively
      with subpicometer spatial and subpicosecond temporal resolution via x-ray
      diffraction (XRD). The spatially periodic femtosecond excitation of a gallium
      arsenide/aluminum gallium arsenide superlattice results in coherent lattice
      motions with a 3.5-picosecond period, which was directly monitored by femtosecond
      x-ray pulses at a 1-kilohertz repetition rate. Small changes (DeltaR/R = 0.01) of
      weak Bragg reflexes (R = 0.005) were detected. The phase and amplitude of the
      oscillatory XRD signal around a new equilibrium demonstrate that displacive
      excitation of the zone-folded acoustic phonons is the dominant mechanism for
      strong excitation.

PMID- 15576619
TI  - Hematotoxicity in workers exposed to low levels of benzene.
AB  - Benzene is known to have toxic effects on the blood and bone marrow, but its
      impact at levels below the U.S. occupational standard of 1 part per million (ppm)
      remains uncertain. In a study of 250 workers exposed to benzene, white blood cell
      and platelet counts were significantly lower than in 140 controls, even for
      exposure below 1 ppm in air. Progenitor cell colony formation significantly
      declined with increasing benzene exposure and was more sensitive to the effects
      of benzene than was the number of mature blood cells. Two genetic variants in key
      metabolizing enzymes, myeloperoxidase and NAD(P)H:quinone oxidoreductase,
      influenced susceptibility to benzene hematotoxicity. Thus, hematotoxicity from
      exposure to benzene occurred at air levels of 1 ppm or less and may be
      particularly evident among genetically susceptible subpopulations.

PMID- 15576620
TI  - A survey method for characterizing daily life experience: the day reconstruction
      method.
AB  - The Day Reconstruction Method (DRM) assesses how people spend their time and how
      they experience the various activities and settings of their lives, combining
      features of time-budget measurement and experience sampling. Participants
      systematically reconstruct their activities and experiences of the preceding day
      with procedures designed to reduce recall biases. The DRM's utility is shown by
      documenting close correspondences between the DRM reports of 909 employed women
      and established results from experience sampling. An analysis of the hedonic
      treadmill shows the DRM's potential for well-being research.

PMID- 15576621
TI  - Conditional use of sex and parthenogenesis for worker and queen production in
      ants.
AB  - The near-ubiquity of sexual reproduction in animal species has long been
      considered a paradox because sexually reproducing individuals transmit only half
      of their genome to their progeny. Here, we show that the ant Cataglyphis cursor
      circumvents this cost by using alternative modes of reproduction for the
      production of reproductive and nonreproductive offspring. New queens are almost
      exclusively produced by parthenogenesis, whereas workers are produced by normal
      sexual reproduction. By selectively using sex for somatic growth and
      parthenogenesis for germline production, C. cursor has taken advantage of the ant
      caste system to benefit from the advantages of both sexual and asexual
      reproduction.

PMID- 15576622
TI  - Crystal structure of a photolyase bound to a CPD-like DNA lesion after in situ
      repair.
AB  - DNA photolyases use light energy to repair DNA that comprises ultraviolet-induced
      lesions such as the cis-syn cyclobutane pyrimidine dimers (CPDs). Here we report
      the crystal structure of a DNA photolyase bound to duplex DNA that is bent by 50
      degrees and comprises a synthetic CPD lesion. This CPD lesion is flipped into the
      active site and split there into two thymines by synchrotron radiation at 100 K.
      Although photolyases catalyze blue light-driven CPD cleavage only above 200 K,
      this structure apparently mimics a structural substate during light-driven DNA
      repair in which back-flipping of the thymines into duplex DNA has not yet taken
      place.

PMID- 15576623
TI  - Regulation of RELM/FIZZ isoform expression by Cdx2 in response to innate and
      adaptive immune stimulation in the intestine.
AB  - Host immune responses to commensal flora and enteric pathogens are known to
      influence gene expression in the intestinal epithelium. Although the Cdx family
      of caudal-related transcription factors represents critical regulators of gene
      expression in the intestinal epithelium, the effect of intestinal immune
      responses on Cdx expression and function has not been determined. We have shown
      that bacterial colonization and Th2 immune stimulation by intestinal nematode
      infection induce expression of the intestinal goblet cell-specific gene RELM
      beta. In this study, we investigated the transcriptional regulation of resistin
      like molecule/found in inflammatory zone (RELM/FIZZ, RELM beta) and its isoforms
      RELM alpha and RELM gamma to ascertain the role of Cdx in modifying intestinal
      gene expression associated with innate and adaptive immune responses. Analysis of
      the RELM beta promoter showed that Cdx2 plays a critical role in basal gene
      activation in vitro. This was confirmed in vivo using transgenic mice, where
      ectopic gastric and hepatic expression of Cdx2 induces expression of RELM beta,
      but not RELM alpha or RELM gamma, exclusively in the stomach. Although there was
      no quantitative change in colonic Cdx2 mRNA expression, protein distribution, or
      phosphorylation of Cdx2, bacterial colonization induced expression of RELM beta,
      but not RELM alpha or RELM gamma. In contrast, parasitic nematode infections
      activated colonic expression of all three RELM isoforms without alteration in
      Cdx2 expression. These results demonstrated that Cdx2 participates in directing
      intestine-specific expression of RELM beta in the presence of commensal bacteria
      and that adaptive Th2 immune responses to intestinal nematode infections can
      activate intestinal goblet cell-specific gene expression independent of Cdx2.

PMID- 15576624
TI  - Expression of the ammonia transporter proteins Rh B glycoprotein and Rh C
      glycoprotein in the intestinal tract.
AB  - Ammonia metabolism is important in multiple aspects of gastrointestinal
      physiology, but the mechanisms of ammonia transport in the gastrointestinal tract
      remain incompletely defined. The present study examines expression of the ammonia
      transporter family members Rh B glycoprotein (RhBG) and Rh C glycoprotein (RhCG)
      in the mouse gastrointestinal tract. Real-time RT-PCR amplification and
      immunoblot analysis identified mRNA and protein for both RhBG and RhCG were
      expressed in stomach, duodenum, jejunum, ileum, and colon. Immunohistochemistry
      showed organ and cell-specific expression of both RhBG and RhCG. In the stomach,
      both RhBG and RhCG were expressed in the fundus and forestomach, but not in the
      antrum. In the forestomach, RhBG was expressed by all nucleated squamous
      epithelial cells, whereas RhCG was expressed only in the stratum germinativum. In
      the fundus, RhBG and RhCG immunoreactivity was present in zymogenic cells but not
      in parietal or mucous cells. Furthermore, zymogenic cell RhBG and RhCG expression
      was polarized, with apical RhCG and basolateral RhBG immunoreactivity. In the
      duodenum, jejunum, ileum, and colon, RhBG and RhCG immunoreactivity was present
      in villous, but not in mucous or crypt cells. Similar to the fundic zymogenic
      cell, RhBG and RhCG expression in villous epithelial cells was polarized when
      apical RhCG and basolateral RhBG immunoreactivity was present. Thus the ammonia
      transporting proteins RhBG and RhCG exhibit cell-specific, axially heterogeneous,
      and polarized expression in the intestinal tract suggesting they function
      cooperatively to mediate gastrointestinal tract ammonia transport.

PMID- 15576625
TI  - Generation and functional significance of CXC chemokines for neutrophil-induced
      liver injury during endotoxemia.
AB  - The hypothesis that the neutrophil chemoattractant CXC chemokines KC and
      macrophage inflammatory protein-2 (MIP-2) are involved in neutrophil
      transmigration and liver injury was tested in C3Heb/FeJ mice treated with
      galactosamine (Gal, 700 mg/kg), endotoxin (ET, 100 microg/kg), or Gal + ET
      (Gal/ET). Hepatic KC and MIP-2 mRNA levels and plasma CXC chemokine
      concentrations were dramatically increased 1.5 h after Gal/ET or ET alone and
      gradually declined up to 7 h. Murine recombinant cytokines (TNF-alpha, IL-1
      alpha, and IL-1 beta), but not Gal/ET, induced CXC chemokine formation in the ET
      resistant C3H/HeJ strain. To assess the functional importance of KC and MIP-2,
      C3Heb/FeJ mice were treated with Gal/ET and control IgG or a combination of anti
      KC and anti-MIP-2 antibodies. Anti-CXC chemokine antibodies did not attenuate
      hepatocellular apoptosis, sinusoidal neutrophil sequestration and extravasation,
      or liver injury at 7 h. Furthermore, there was no difference in liver injury
      between BALB/cJ wild-type and CXC receptor-2 gene knockout (CXCR2-/-) mice
      treated with Gal/ET. The higher neutrophil count in livers of CXCR2-/- than in
      wild-type mice after Gal/ET was caused by the elevated number of neutrophils
      located in sinusoids of untreated CXCR2-/- animals. The pancaspase inhibitor Z
      Val-Ala-Asp-fluoromethylketone eliminated Gal/ET-induced apoptosis and neutrophil
      extravasation and injury but not CXC chemokine formation. Thus Gal/ET induced
      massive, cytokine-dependent CXC chemokine formation in the liver. However,
      neutrophil extravasation and injury occurred in response to apoptotic cell injury
      at 6-7 h and was independent of CXC chemokine formation.

PMID- 15576626
TI  - Detection of early central circulatory transits in patients with cirrhosis by
      gamma variate fit of indicator dilution profiles.
AB  - Patients with cirrhosis have hyperdynamic circulation with abnormally distributed
      blood volume and widespread arteriovenous communications. We aimed to detect
      possible very early (i.e., before 4 s) and early (i.e., after 4 s) central
      circulatory transits and their potential influence on determination of central
      and arterial blood volume (CBV). Thirty-six cirrhotic patients and nineteen
      controls without liver disease undergoing hemodynamic catheterization were given
      central bolus injections of albumin with different labels. Exponential and gamma
      variate fits were applied to the indicator dilution curves, and the relations
      between flow, circulation times, and volumes were established according to
      kinetic principles. No significant very early central circulatory transits were
      identified. In contrast, early (i.e., 4 s to maximal) transits corresponding to a
      mean of 5.1% (vs. 0.8% in controls; P < 0.005) of cardiac output (equivalent to
      0.36 vs. 0.05 l/min; P < 0.01) were found in cirrhotic patients. These early
      transits averaged 7.7 vs. 12.7 and 17.2 s of ordinary central transits of
      cirrhotic patients and controls, respectively (P < 0.001). Early transits were
      directly correlated to the alveolar-arterial oxygen difference in the cirrhotic
      patients (r = 0.46, P < 0.01) but not in controls (r = 0.04; not significant).
      There was good agreement between the CBV determined by the conventional indicator
      dilution method and that determined by separation of early and ordinary transits
      by the gamma variate fit method (1.51 vs. 1.53 liter; not significant). In
      conclusion, no very early central circulatory transits were identified in
      cirrhotic patients. A significant part of the cardiac output undergoes an early
      transit, probably through pulmonary shunts or areas with low ventilation
      perfusion ratios in cirrhotic patients. Composite determination of CBV by the
      gamma variate fit method is in close agreement with established kinetic methods.
      The study provides further evidence of abnormal central circulation in cirrhosis.

PMID- 15576627
TI  - HCO3- secretion in the esophageal submucosal glands.
AB  - The mammalian esophagus has the capacity to secrete a HCO(3)(-) and mucin-rich
      fluid in the esophageal lumen. These secretions originate from the submucosal
      glands (SMG) and can contribute to esophageal protection against refluxed gastric
      acid. The cellular mechanisms by which glandular cells achieve these secretions
      are largely unknown. To study this phenomenon, we used the pH-stat technique to
      measure luminal alkali secretion in an isolated, perfused pig esophagus
      preparation. Immunohistochemistry was used to localize receptors and transporters
      involved in HCO(3)(-) transport. The SMG-bearing esophagus was found to have
      significant basal alkali secretion, predominantly HCO(3)(-), which averaged 0.21
      +/- 0.04 microeq.h(-1).cm(-2). This basal secretion was doubled when stimulated
      by carbachol but abolished by HCO(3)(-) or Cl(-) removal. Basal- and carbachol
      stimulated secretions were also blocked by serosal application of atropine,
      pirenzipine, DIDS, methazolamide, and ethoxzolamide. The membrane-impermeable
      carbonic anhydrase inhibitor benzolamide, applied to the serosal bath, partially
      inhibited basal HCO(3)(-) secretion and blocked the stimulation by carbachol.
      Immunohistochemistry using antibodies to M(1) cholinergic receptor or carbonic
      anhydrase-II enzyme showed intense labeling of duct cells and serous demilunes
      but no labeling of mucous cells. Labeling with an antibody to Na(+)-(HCO(3)(
      ))(n) (rat kidney NBC) was positive in ducts and serous cells, whereas labeling
      for Cl(-)/HCO(3)(-) exchanger (AE2) was positive in duct cells but less
      pronounced in serous cells. These data indicate that duct cells and serous
      demilunes of SMG play a role in HCO(3)(-) secretion, a process that involves M(1)
      cholinergic receptor stimulation. HCO(3)(-) transport in these cells is dependent
      on cytosolic and serosal membrane-bound carbonic anhydrase. HCO(3)(-) secretion
      is also dependent on serosal Cl(-) and is mediated by DIDS-sensitive
      transporters, possibly NBC and AE2.

PMID- 15576628
TI  - Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with
      preference for basic amino acids.
AB  - One of the most important tasks of molecular pharmacology is the deorphanization
      of the large number of G-protein-coupled receptors with unidentified endogenous
      agonists. We recently reported the cloning and analysis of expression of a novel
      human family C G-protein-coupled receptor, termed hGPRC6A. To identify agonists
      at this orphan receptor, we faced the challenges of achieving surface expression
      in mammalian cell lines and establishing an appropriate functional assay.
      Generating a chimeric receptor construct, h6A/5.24, containing the ligand binding
      amino-terminal domain (ATD) of hGPRC6A with the signal transducing transmembrane
      and C terminus of the homologous goldfish 5.24 receptor allowed us to overcome
      these obstacles. Homology modeling of the hGPRC6A ATD based on the crystal
      structure of the metabotropic glutamate receptor subtype 1 predicted interaction
      with alpha-amino acids and was employed to rationally select potential ligands.
      Measurement of Ca2+-dependent chloride currents in Xenopus laevis oocytes
      facilitated the deorphanization of h6A/5.24 and identification of L-alpha-amino
      acids as agonists. The most active agonists were basic L-alpha-amino acids, L
      Arg, L-Lys, and L-ornithine, suggesting that these may function as endogenous
      signaling molecules. Measurement of intracellular calcium in tsA cells expressing
      h6A/5.24 allowed determination of EC50 values, which confirmed the agonist
      preferences observed in oocytes. Cloning, cell surface expression and
      deorphanization of the mouse ortholog further reinforces the assignment of the
      agonist preferences of hGPRC6A. This study demonstrates the utility of a chimeric
      receptor approach in combination with molecular modeling, for elucidating agonist
      interaction with GPRC6A, a novel family C G-protein-coupled receptor.

PMID- 15576629
TI  - Constitutive expression of peroxisome proliferator-activated receptor alpha
      regulated genes in dwarf mice.
AB  - Defects in growth hormone secretion or signaling in mice are associated with
      decreased body weights (dwarfism), increased longevity, increased resistance to
      stress, and decreases in factors that contribute to cardiovascular disease and
      cancer. Peroxisome proliferators (PP) alter a subset of these changes in wild
      type mice through activation of the nuclear receptor family member PP-activated
      receptor alpha (PPARalpha). We tested the hypothesis that an overlap in the
      transcriptional programs between untreated dwarf mice and PP-treated wild-type
      mice underlies these similarities. Using transcript profiling, we observed a
      statistically significant overlap in the expression of genes differentially
      regulated in control Snell dwarf mice (Pit-1dw) compared with phenotypically
      normal heterozygote (+/dw) control mice and those altered by the PP 4-chloro-6
      (2,3-xylidino)-2-pyrimidinyl)thioacetic acid (WY-14,643) in +/dw mice. The genes
      included those involved in beta- and omega-oxidation of fatty acids (Acox1,
      Cyp4a10, Cyp4a14) and those involved in stress responses (the chaperonin, T
      complex protein1epsilon) and cardiovascular disease (fibrinogen). The levels of
      some of these gene products were also altered in other dwarf mouse models,
      including Ames, Little, and growth hormone receptor-null mice. The constitutive
      increases in PPARalpha-regulated genes may be partly caused by increased
      expression of PPARalpha mRNA and protein as observed in the livers of control
      Snell dwarf mice. These results indicate that some of the beneficial effects
      associated with the dwarf phenotype may be caused by constitutive activation of
      PPARalpha and regulated genes.

PMID- 15576630
TI  - DNA damage effects of a polyamide-CBI conjugate in SV40 virions.
AB  - Polyamides are a class of synthetic molecules that exhibit high-affinity,
      sequence-specific reversible binding in the DNA minor groove but are incapable of
      inducing DNA damage. In cell-free systems, polyamides have been shown to regulate
      gene expression by activation, repression, and antirepression. However,
      effectiveness in cell culture has met with limited success and seems to be cell
      dependent. By combining a polyamide with a moiety of a DNA-alkylating agent of
      the cyclopropylpyrroloindole (CPI) family, a conjugate molecule [polyamide 1-CBI
      (1-(chloromethyl)-5-hydroxyl-1,2-dihydro-3H-benz[e]indole) conjugate] capable of
      sequence-specific DNA alkylation was shown to exhibit cellular activity (i.e.,
      cell-growth inhibition and cell-cycle arrest) in mammalian cells. These effects,
      however, occur at concentrations several orders of magnitude higher than those of
      its parent CPI agent adozelesin. In addition, 1-CBI is able to interact sequence
      specifically with viral DNA and inhibit SV40 DNA replication in infected BSC-1
      (African green monkey kidney epithelial) cells, albeit at a greatly reduced
      ability compared with its CPI parent. On the basis of results from previous
      studies, we tested whether pretreatment of virus with 1-CBI, compared with direct
      treatment of infected cells, would enhance its cellular activity. Therefore,
      using SV40 virions as a model system, we examined the ability of this conjugate
      molecule to penetrate SV40 virions and damage viral DNA. Our results demonstrate
      that 1-CBI is able to damage encapsidated SV40 DNA. Both DNA replication and
      virus production are effectively inhibited in a concentration-dependent manner
      after infection of BSC-1 cells with 1-CBI-pretreated virions. It is surprising
      that, unlike in mammalian cells, the relative activity of 1-CBI in SV40 virions
      is comparable with that of the highly cytotoxic CPI agent adozelesin. Because 1
      CBI is able to efficiently penetrate virions and damage DNA, these findings may
      provide the framework for the development of polyamide-based antiviral agents
      with enhanced sequence-preference capabilities.

PMID- 15576631
TI  - Urinary trypsin inhibitor protects against systemic inflammation induced by
      lipopolysaccharide.
AB  - Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely
      used as a drug for patients with acute inflammatory disorders such as
      disseminated intravascular coagulation, shock, and pancreatitis in Japan. Recent
      studies have demonstrated that serine protease inhibitors may play an anti
      inflammatory role beyond merely an inhibitory action on neutrophil elastase at
      the site of inflammation at least in vitro. To clarify the direct contributions
      of UTI to inflammatory condition in vivo, we analyzed its roles in experimental
      systemic inflammatory response induced by intraperitoneal administration of
      lipopolysaccharide (LPS) using UTI deficient (-/-) mice and corresponding wild
      type (WT) mice. After LPS (1 mg/kg) challenge, UTI (-/-) mice revealed a
      significant elevation of plasma fibrinogen and fibrinogen/fibrin degradation
      products and a decrease in white blood cell counts compared with WT mice. LPS
      treatment induced more severe neutrophilic inflammation in the lung and the
      kidney obtained from UTI (-/-) mice than in those from WT mice, which was
      confirmed by histological examination. The protein levels of proinflammatory
      mediators, such as macrophage chemoattractant protein (MCP)-1 in the lungs, MCP-1
      and keratinocyte chemoattractant (KC) in the kidneys, and interleukin-1beta,
      macrophage inflammatory protein-2, MCP-1, and KC in the liver, were significantly
      greater in UTI (-/-) mice than in WT mice after LPS challenge. Our results
      suggest that UTI protects against systemic inflammatory response and subsequent
      organ injury induced by bacterial endotoxin, at least partly through the
      inhibition of the enhanced expression of proinflammatory cytokines and
      chemokines.

PMID- 15576632
TI  - Nuclear factor-kappaB decoy oligodeoxynucleotides prevent acute lung injury in
      mice with cecal ligation and puncture-induced sepsis.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) plays a key role in
      expression of many inflammatory genes responsible for the pathophysiology of
      sepsis-induced acute lung injury. We investigated whether the introduction of
      synthetic double-stranded oligodeoxynucleotides (ODNs) with consensus NF-kappaB
      sequence as transcription factor decoy can prevent acute lung injury with
      suppression of pulmonary expression of multiple genes involved in its
      pathological process in a cecal ligation and puncture septic mouse model. NF
      kappaB decoy ODNs were introduced with the aid of the hemagglutinating virus of
      Japan-envelope vector method. Northern blot analysis indicated that transfection
      of NF-kappaB decoy ODN, but not of its scrambled form, resulted in a significant
      inhibition of sepsis-induced gene overexpression of inducible nitric-oxide
      synthase (iNOS), cyclooxygenase-2, histamine H(1)-receptor, platelet-activating
      factor receptor, and bradykinin B(1) and B(2) receptors in lung Histological
      damage in lungs tissues. (wall thickening, inflammatory infiltrate, and
      hemorrhage), increased pulmonary vascular permeability, and blood gas exchange
      impairment were clearly documented in mice after cecal ligation and puncture.
      These changes were strongly eliminated by the introduction of NF-kappaB decoy but
      not of scrambled ODN. The effects of the iNOS inhibitor FR260330 on these
      histological and functional derangements compared unfavorably with those of NF
      kappaB decoy ODN transfection. Our results suggest that ODN decoy, acting as in
      vivo competitor for the transcription factor's ability to bind to cognate
      recognition sequence, may represent an effective strategy in the treatment of
      septic acute lung injury.

PMID- 15576633
TI  - The role of N-linked glycosylation in protein folding, membrane targeting, and
      substrate binding of human organic anion transporter hOAT4.
AB  - We used a novel approach to evaluate how the addition/acquisition and
      processing/modification of N-linked oligosaccharides play a role in the
      functional maturation of human organic anion transporter hOAT4. Inhibition of
      acquisition of oligosaccharides in hOAT4 by mutating asparagine to glutamine and
      by tunicamycin treatment was combined with the expression of wild-type hOAT4 in a
      series of mutant Chinese hamster ovary (CHO)-Lec cells defective in the different
      steps of glycosylation processing. We showed that both the disruption of the
      glycosylation sites by mutagenesis and the inhibition of glycosylation by
      tunicamycin treatment resulted in a nonglycosylated hOAT4, which was unable to
      target to the cell surface. In contrast, hOAT4 synthesized in mutant CHO-Lec
      cells, carrying different structural forms of sugar moieties (mannose-rich in
      Lec1 cells, sialic acid-deficient in Lec2 cells, and sialic acid/galactose
      deficient in Lec8 cells) were able to traffic to the cell surface. However, hOAT4
      expressed in CHO-Lec1 cells had significantly lower binding affinity for its
      substrates compared with that expressed in parental CHO cells. This study
      provided novel information that addition/acquisition of oligosaccharides but not
      the processing of the added oligosaccharides participates in the membrane
      insertion of hOAT4. Processing of added oligosaccharides from mannose-rich type
      to complex type is important for enhancing the binding affinity of hOAT4 for its
      substrates. Glycosylation could therefore serve as a means to specifically
      regulate hOAT4 function in vivo.

PMID- 15576634
TI  - Role of the C terminus in neuropeptide Y Y1 receptor desensitization and
      internalization.
AB  - We have studied truncation mutants of the rat neuropeptide Y (NPY) Y1 receptor
      lacking four (Thr361stop, Y1T361*) or eight (Ser352stop, Y1S352*) potential
      serine/threonine C-terminal phosphorylation sites. NPY-stimulated hemagglutinin
      tagged Y1, Y1T361*, and Y1S352* receptors all efficiently activated G proteins in
      Chinese hamster ovary (CHO) cell membranes, but desensitization after NPY
      pretreatment was only prevented in the HAY1S352* clone. In transfected colonic
      carcinoma epithelial layers, functional Y1 and Y1T361* peptide YY responses
      became more transient as the agonist concentration increased, whereas those
      mediated by the Y1S352* receptor remained sustained. NPY-stimulated HAY1 receptor
      phosphorylation was increased by transient overexpression of G protein-coupled
      receptor kinase 2, and only Ser352stop truncation abolished this response in CHO
      or human embryonic kidney (HEK) 293 cells. Rapid internalization of cell-surface
      HAY1 receptors in HEK293 cells was observed in response to agonist, resulting in
      partial colocalization with transferrin, a marker for clathrin-mediated
      endocytosis and recycling. It is surprising that both truncated receptors were
      constitutively internalized, predominantly in transferrin-positive compartments.
      NPY increased cell-surface localization of HAY1S352* receptors, whereas the
      distribution of both mutants was unaltered by BIBO3304. Recruitment of green
      fluorescent protein-tagged beta-arrestin2 to punctate endosomes was observed only
      for HAY1 and HAY1T361* receptors and solely under NPY-stimulated conditions.
      Thus, the key C-terminal sequence between Ser352 and Lys360 is a major site for
      Y1 receptor phosphorylation, is critical for its desensitization, and contributes
      to the association between the receptor and beta-arrestin proteins. However,
      additional beta-arrestin-independent mechanisms control Y1 receptor trafficking
      under basal conditions.

PMID- 15576635
TI  - Prostaglandin E synthases in zebrafish.
AB  - OBJECTIVE: Prostaglandin E synthases (PGESs) are being explored as
      antiinflammatory drug targets as alternatives to cyclooxygenase (COX)-2. Located
      downstream of the cyclooxygenases, PGESs catalyze PGE(2) formation, and deletion
      of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the
      developmental expression of COX and PGES in zebrafish. METHODS AND RESULTS: We
      cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic
      regions of chromosomes 23 and 5. cPGES was widely expressed during development
      and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and
      intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the
      vasculature of the aortic arch. However, the enzymes were anatomically segregated
      within the vessel wall. Experiments with antisense morpholinos and with
      nonsteroidal antiinflammatory drugs suggest that these genes may not be critical
      for development. CONCLUSIONS: mPGES-1 is developmentally coregulated with COX-2
      in vasculature. Given the high fecundidity and translucency of the zebrafish,
      this model may afford a high throughput system for characterization of novel PGES
      inhibitors. Microsomal prostaglandin E synthase (mPGES)-1, located downstream of
      COX-2, may represent a novel antiinflammatory drug target. Zebrafish cytosolic
      (c) PGES-1 and COX-1 were coordinately expressed; mPGES-1 and COX-2 were
      expressed particularly in the vasculature. Zebrafish may afford a high throughput
      system for detection of novel PGES inhibitors.

PMID- 15576636
TI  - Postprandial lipoprotein changes in patients taking antiretroviral therapy for
      HIV infection.
AB  - OBJECTIVE: Dyslipidemia is common among patients receiving antiretroviral therapy
      for HIV infection. The purpose of this study was to determine whether
      postprandial lipemia contributes to the dyslipidemia observed in HIV-positive
      patients taking antiretroviral therapy. METHODS AND RESULTS: A standardized fat
      load was administered to 65 subjects (group 1 35 HIV-positive subjects receiving
      protease inhibitors [PIs]; group 2 20 HIV-positive subjects not receiving PIs;
      group 3 10 HIV-negative controls). Serum triglycerides, retinyl palmitate, and
      lipoproteins were measured using enzymatic and nuclear magnetic resonance
      spectroscopic techniques. Compared with HIV-negative controls, peak postprandial
      retinyl palmitate and large very low-density lipoprotein (VLDL) levels occurred
      later in both HIV-positive groups, and a delayed decrease in serum triglycerides
      was observed. However, postprandial areas under the curve (AUCs) for
      triglycerides, retinyl palmitate, chylomicrons, and large VLDL were similar.
      Postprandial AUCs for intermediate-density lipoproteins (IDLs) and low-density
      lipoproteins (LDLs) were higher in group 1 than groups 2 and 3 (all P<0.035).
      CONCLUSIONS: Postprandial clearance of triglyceride-rich lipoproteins is delayed
      in HIV-positive individuals receiving antiretroviral therapy. Compared with HIV
      positive individuals not on PIs, those taking PIs do not have increased
      postprandial triglyceride-rich lipoproteins but do have increased postprandial
      IDLs and LDLs. An oral fat load was administered to 55 HIV-positive and 10 HIV
      negative individuals. Postprandial clearance of triglyceride-rich lipoproteins
      was delayed in HIV-positive individuals. Compared with HIV-positive subjects not
      on PIs, those taking PIs do not have increased postprandial triglyceride-rich
      lipoproteins but do have increased postprandial intermediate-density and low
      density lipoproteins.

PMID- 15576637
TI  - Acute effect of high-fat meal on endothelial function in moderately dyslipidemic
      subjects.
AB  - OBJECTIVE: Hypercholesterolemia markedly impairs endothelial function. Whether
      this is the case for hypertriglyceridemia is less clear, however, and limited
      evidence exists on the effect of an acute increase in triglyceridemia caused by a
      high-fat meal. METHODS AND RESULTS: In 16 normotensive subjects with an untreated
      mild hypertriglyceridemia and dyslipidemia and in 7 normal controls, we measured
      radial artery diameter and blood flow by an echo-tracking device (NIUS02). Data
      were obtained at baseline, at the release of a 4-minute ischemia of the hand,
      which causes an increase in arterial diameter dependent on nitric oxide (NO)
      secretion, and at the release of a 12-minute exclusion of the arm by an arm cuff
      to obtain a larger increase in arterial diameter mainly of nonendothelial nature.
      Measurements were performed before and 6 hours after a high-fat meal (680
      kcal/m(2) body surface; 82% lipids). In mild dyslipidemic hypertriglyceridemic
      subjects, the high-fat meal did not alter baseline blood pressure (beat-to-beat
      finger measurement), heart rate, radial artery diameter, and blood flow. It also
      did not alter the increase in blood flow induced by the 4-minute ischemia
      (+42.7+/-10.4 and +43.7+/-10.4 mL/min), whereas it markedly attenuated the
      concomitant increase in arterial diameter (+0.31+/-0.06 versus 0.13+/-0.06 mm;
      P<0.05). The alteration of the diameter response did not correlate with changes
      in total cholesterol, but it showed a significant correlation with the increase
      in serum triglycerides induced by high-fat meal (r=0.49, P<0.05). This
      attenuation was not seen in control subjects and in subjects in whom measurements
      were repeated after a 6-hour observation period. It was also not paralleled by an
      alteration of the endothelially independent response to a 12-minute ischemia
      whose larger effects on arterial diameter and blood flow were similar before and
      after the high-fat meal. CONCLUSIONS: Endothelial function is markedly impaired
      by a high-fat meal that causes an acute hypertriglyceridemia. This impairment is
      evident in dyslipidemic patients with baseline hypertriglyceridemia but not in
      normotriglyceridemic controls. An oral fat load was administered to 55 HIV
      positive and 10 HIV-negative individuals. Postprandial clearance of triglyceride
      rich lipoproteins was delayed in HIV-positive individuals. Compared with HIV
      positive subjects not on PIs, those taking PIs do not have increased postprandial
      triglyceride-rich lipoproteins but do have increased postprandial intermediate
      density and low-density lipoproteins. Hypercholesterolemia impairs endothelial
      function, whereas the effect of hypertriglyceridemia is less clear. In
      normotensive subjects with an untreated hypertriglyceridemia and
      hypercholesterolemia, we measured endothelial function before and 6 hours after a
      high-fat meal. The results demonstrate that in moderately dyslipidemic patients,
      endothelial function is impaired by acute hypertriglyceridemia.

PMID- 15576638
TI  - Pharmacological inhibition and genetic deficiency of plasminogen activator
      inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling.
AB  - OBJECTIVE: To test the hypothesis that pharmacological plasminogen activator
      inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone
      system-induced cardiovascular injury, the effect of a novel orally active small
      molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin
      (Ang) II-induced vascular remodeling and cardiac fibrosis. METHODS AND RESULTS:
      Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang
      II (1 mug/h) subcutaneous, vehicle+PAI-039 (1 mg/g chow), or Ang II+PAI-039
      during high-salt intake for 8 weeks. Ang II caused significant medial,
      adventitial, and aortic wall thickening compared with vehicle. PAI-039 attenuated
      Ang II-induced aortic remodeling without altering the pressor response to Ang II.
      Ang II increased heart/body weight ratio and cardiac fibrosis. PAI-039 did not
      attenuate the effect of Ang II on cardiac hypertrophy and increased fibrosis. The
      effect of PAI-039 on Ang II/salt-induced aortic remodeling and cardiac fibrosis
      was comparable to the effect of genetic PAI-1 deficiency. Ang II increased aortic
      mRNA expression of PAI-1, collagen I, collagen III, fibronectin, osteopontin,
      monocyte chemoattractant protein-1, and F4/80; PAI-039 significantly decreased
      the Ang II-induced increase in aortic osteopontin expression at 8 weeks.
      CONCLUSIONS: This study demonstrates that pharmacological inhibition of PAI-1
      protects against Ang II-induced aortic remodeling. Future studies are needed to
      determine whether the interactive effect of Ang II/salt and reduced PAI-1
      activity on cardiac fibrosis is species-specific. In this study, the effect of
      pharmacological PAI-1 inhibition in a mouse model of Ang II-induced vascular
      remodeling and cardiac fibrosis was examined. PAI-1 inhibition significantly
      attenuated Ang II-induced aortic medial and wall thickening, but not cardiac
      hypertrophy, and enhanced Ang II/salt-induced cardiac fibrosis.

PMID- 15576639
TI  - Superoxide dismutase inhibits the expression of vascular cell adhesion molecule-1
      and intracellular cell adhesion molecule-1 induced by tumor necrosis factor-alpha
      in human endothelial cells through the JNK/p38 pathways.
AB  - OBJECTIVE: Expression of adhesion molecules on endothelial cells and subsequent
      leukocyte recruitment are critical early events in the development of
      atherosclerosis. We tried to study possible effects of Cu/Zn superoxide dismutase
      (SOD) on adhesion molecule expression and its underlying mechanism in the
      prevention and treatment of cardiovascular disorders. METHODS AND RESULTS: Human
      aortic endothelial cells (HAECs) were transfected with adenovirus carrying the
      human SOD gene (AdSOD) to investigate whether SOD expression in HAECs attenuated
      tumor necrosis factor (TNF)-alpha-induced reactive oxygen species production and
      adhesion molecule expression and to define the mechanisms involved. SOD
      expression significantly suppressed TNF-alpha-induced expression of vascular cell
      adhesion molecule-1 and intercellular cell adhesion molecule-1 and reduced the
      binding of the human neutrophils to TNF-alpha-stimulated HAECs. SOD expression
      suppressed c-JUN N-terminal kinase and p38 phosphorylation. It also attenuated
      intracellular superoxide anion production and NADPH oxidase activity in TNF-alpha
      treated HAECs. CONCLUSIONS: These results provide evidence that SOD expression in
      endothelial cells attenuates TNF-alpha-induced superoxide anion production and
      adhesion molecule expression, and that this protective effect is mediated by
      decreased JNK and p38 phosphorylation and activator protein-1 and nuclear factor
      kappaB inactivation. These results suggest that SOD has antiinflammatory
      properties and may play important roles in the prevention of atherosclerosis and
      inflammatory response. Superoxide dismutase overexpression in endothelial cells
      attenuates tumor necrosis factor alpha-induced superoxide anion production and
      adhesion molecule expression, and this effect is mediated by decreased JNK and
      p38 phosphorylation and AP-1 and nuclear factor B inactivation. These results
      suggest that superoxide dismutase may play an important role in the prevention of
      atherosclerosis and inflammatory response.

PMID- 15576640
TI  - Lower doses of estrogen replacement therapy and the risk of cardiovascular
      disease.

PMID- 15576641
TI  - Glimpse of the secret life of the plaque.

PMID- 15576642
TI  - Proteolysis of pericellular matrix: a process linking inflammation to plaque
      destabilization and rupture.

PMID- 15576643
TI  - Propagation of arterial thrombi: local and remote contributory factors.

PMID- 15576644
TI  - 24(S),25-epoxycholesterol--a potential friend.

PMID- 15576647
TI  - Fetal liver-sparing cardiovascular adaptations linked to mother's slimness and
      diet.
AB  - Fetal adaptations to impaired maternoplacental nutrient supply include altered
      regional blood flow. Whether such responses operate within the normal range of
      maternal body composition or diet is unknown, but any change in fetal liver
      perfusion could alter hepatic development, with long-term consequences for the
      risk of cardiovascular and metabolic disease. In 381 low-risk pregnancies, we
      found that the fetuses of slimmer mothers with lower body fat stores and those
      eating an unbalanced diet had greater liver blood flow and shunted less blood
      away from the liver through the ductus venosus at 36 weeks gestation.
      Consequences of such "liver-sparing" may underlie the increased cardiovascular
      risk of people whose mothers were slimmer and had lower body fat stores in
      pregnancy.

PMID- 15576648
TI  - Targeting to C-terminal myosin heavy chain may explain mechanotransduction
      involving focal adhesion kinase in cardiac myocytes.
AB  - Focal adhesion kinase (Fak) has been implicated as a signaling molecule involved
      in the early response of cardiac myocytes to mechanical stress. The mechanism of
      Fak activation by mechanical stimuli is not clear. In this study, we report the
      load-induced Fak activation and its association with myosin heavy chain in
      cardiac myocytes. Pressure overload lasting from 3 to 60 minutes was shown to
      induce Fak phosphorylation at Tyr-397, -576/7, -861, and -925 as detected by
      phosphospecific antibodies. This was paralleled by increases of Fak/Src
      association and Src activity (Tyr-418 phosphorylation). Yeast two-hybrid
      screening of an adult rat cDNA library revealed an interaction between Fak and C
      terminal coiled-coil region of alpha-myosin heavy chain. This was confirmed by
      pulldown assay with GST-C-terminal myosin fragment and native Fak from rat left
      ventricle. Such interaction was confirmed by coimmunoprecipitation assay with
      anti-Fak and anti-heavy chain cardiac myosin antibodies, confocal microscopy of
      double-labeled isolated cardiac myocytes and immunoelectron microscopy with anti
      Fak antibody. Fak activation by mechanical stress was accompanied by a reduction
      of Fak/myosin heavy chain association and its relocation at subcellular sites
      such as costameres, Z-discs, and nuclei. Thus, our present data identify Fak
      interaction with C-terminal region of myosin heavy chain adding comprehensive
      data on Fak activation by mechanical stress and mechanotransduction in cardiac
      myocytes.

PMID- 15576649
TI  - Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and
      infarct regression in transgenic mice.
AB  - Restriction point transit and commitment to a new round of cell division is
      regulated by the activity of cyclin-dependent kinase 4 and its obligate
      activating partners, the D-type cyclins. In this study, we examined the ability
      of D-type cyclins to promote cardiomyocyte cell cycle activity. Adult transgenic
      mice expressing cyclin D1, D2, or D3 under the regulation of the alpha cardiac
      myosin heavy chain promoter exhibited high rates of cardiomyocyte DNA synthesis
      under baseline conditions. Cardiac injury in mice expressing cyclin D1 or D3
      resulted in cytoplasmic cyclin D accumulation, with a concomitant reduction in
      the level of cardiomyocyte DNA synthesis. In contrast, cardiac injury in mice
      expressing cyclin D2 did not alter subcellular cyclin localization. Consequently,
      cardiomyocyte cell cycle activity persisted in injured hearts expressing cyclin
      D2, ultimately resulting in infarct regression. These data suggested that
      modulation of D-type cyclins could be exploited to promote regenerative growth in
      injured hearts.

PMID- 15576650
TI  - Connexin 43 downregulation and dephosphorylation in nonischemic heart failure is
      associated with enhanced colocalized protein phosphatase type 2A.
AB  - In nonischemic heart failure (HF), ventricular tachycardia initiates by a
      nonreentrant mechanism, but there is altered conduction (that could lead to re
      entry) that could arise from changes in gap junctional proteins, especially
      connexin43 (Cx43). We studied Cx43 expression and phosphorylation state in the
      left ventricle (LV) from an arrhythmogenic rabbit model of nonischemic HF and
      from patients with HF attributable to idiopathic dilated cardiomyopathy. We also
      investigated the role of protein phosphatases that dephosphorylate Cx43--PP1 and
      PP2A. In HF rabbit LV, Cx43 mRNA and total protein were decreased by 29% and 34%,
      respectively (P<0.05 and P<0.001). In controls, Cx43 was primarily in the
      phosphorylated state, but with HF there was a 64% increase in nonphosphorylated
      Cx43 (Cx43-NP, normalized to total Cx43; P<0.05). Similar results were noted in
      HF rabbit myocytes (P<0.05) and in human idiopathic dilated cardiomyopathy LV
      (P<0.05). We found that PP1 and PP2A colocalized with Cx43 in rabbit LV. With HF,
      the level of colocalized PP2A increased >2.5-fold (P<0.002), whereas colocalized
      PP1 was unchanged. We also found intercellular coupling (assessed by Lucifer
      Yellow dye transfer) was markedly reduced in HF. However, okadaic acid (10
      nmol/L) reduced the amount of Cx43-NP and significantly improved cell coupling in
      HF. Thus, in nonischemic HF in rabbits and humans, there is a decrease in both
      Cx43 expression and phosphorylation that contributes to uncoupling. Increased
      levels of PP2A that colocalize with Cx43 can underlie enhanced levels of Cx43-NP
      in HF. Modulation of Cx43 phosphorylation may be a potential therapeutic target
      to improve conduction in HF.

PMID- 15576651
TI  - cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation
      by NOS3-dependent mechanism.
AB  - Beta-adrenergic agonists stimulate cardiac contractility and simultaneously blunt
      this response by coactivating NO synthase (NOS3) to enhance cGMP synthesis and
      activate protein kinase G (PKG-1). cGMP is also catabolically regulated by
      phosphodiesterase 5A (PDE5A). PDE5A inhibition by sildenafil (Viagra) increases
      cGMP and is used widely to treat erectile dysfunction; however, its role in the
      heart and its interaction with beta-adrenergic and NOS3/cGMP stimulation is
      largely unknown. In nontransgenic (control) murine in vivo hearts and isolated
      myocytes, PDE5A inhibition (sildenafil) minimally altered rest function. However,
      when the hearts or isolated myocytes were stimulated with isoproterenol, PDE5A
      inhibition was associated with a suppression of contractility that was coupled to
      elevated cGMP and increased PKG-1 activity. In contrast, NOS3-null hearts or
      controls with NOS inhibited by N(G)-nitro-L-arginine methyl ester, or soluble
      guanylate cyclase (sGC) inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1
      one, showed no effect of PDE5A inhibition on beta-stimulated contractility or PKG
      1 activation. This lack of response was not attributable to altered PDE5A gene or
      protein expression or in vitro PDE5A activity, but rather to an absence of sGC
      generated cGMP specifically targeted to PDE5A catabolism and to a loss of PDE5A
      localization to z-bands. Re-expression of active NOS3 in NOS3-null hearts by
      adenoviral gene transfer restored PDE5A z-band localization and the
      antiadrenergic efficacy of PDE5A inhibition. These data support a novel
      regulatory role of PDE5A in hearts under adrenergic stimulation and highlight
      specific coupling of PDE5A catabolic regulation with NOS3-derived cGMP
      attributable to protein subcellular localization and targeted synthetic/catabolic
      coupling.

PMID- 15576652
TI  - Anatomical mapping of white matter hyperintensities (WMH): exploring the
      relationships between periventricular WMH, deep WMH, and total WMH burden.
AB  - BACKGROUND AND PURPOSE: MRI segmentation and mapping techniques were used to
      assess evidence in support of categorical distinctions between periventricular
      white matter hyperintensities (PVWMH) and deep WMH (DWMH). Qualitative MRI
      studies generally identify 2 categories of WMH on the basis of anatomical
      localization. Separate pathophysiologies and behavioral consequences are often
      attributed to these 2 classes of WMH. However, evidence to support these
      empirical distinctions has not been rigorously sought. METHODS: MRI analysis of
      55 subjects included quantification of WMH volume, mapping onto a common
      anatomical image, and spatial localization of each WMH voxel. WMH locations were
      then divided into PVWMH and DWMH on the basis of distance from the lateral
      ventricles and correlations, with total WMH volume determined. Periventricular
      distance histograms of WMH voxels were also calculated. RESULTS: PVWMH and DWMH
      were highly correlated with total WMH (R2>0.95) and with each other (R2>0.87).
      Mapping of all WMH revealed smooth expansion from around central cerebrospinal
      fluid spaces into more distal cerebral white matter with increasing WMH volume.
      CONCLUSIONS: PVWMH, DWMH, and total WMH are highly correlated with each other.
      Moreover, spatial analysis failed to identify distinct subpopulations for PVWMH
      and DWMH. These results suggest that categorical distinctions between PVWMH and
      DWMH may be arbitrary, and conclusions regarding individual relationships between
      causal factors or behavior for PVWMH and DWMH may more accurately reflect total
      WMH volume relationships.

PMID- 15576653
TI  - Toll-like receptor 4 Asp299Gly gene polymorphism and risk of atherothrombosis.
AB  - BACKGROUND AND PURPOSE: Recent findings of an association between a functional
      toll-like receptor 4 (TLR4) D299G gene variant and reduced risk of
      atherothrombotic disorders have generated great interest. METHODS: We evaluated
      the TLR4 D299G polymorphism among 695 individuals with incident myocardial
      infarction (MI) or stroke and among 695 age- and smoking-matched individuals who
      remained free of reported cardiovascular disease during follow-up within the
      Physicians' Health Study. RESULTS: Overall, we observed little evidence of
      association between the D299G polymorphism and risk of any atherothrombotic event
      (P=0.25), incident MI (P=0.89), or stroke (P=0.09), assuming an additive model.
      Adjusting for traditional cardiovascular risk factors or assuming a dominant
      model yielded similar null findings. Whereas the observed carrier frequency of
      the D299G polymorphism in our data (13.0%) is consistent with those observed in
      most other studies, it was higher than the 6.8% carrier frequency observed in the
      initial study that suggested a protective effect for this gene variant. Thus,
      this former association may have been caused, in part, by an underestimation of
      the control frequency. CONCLUSIONS: In contrast to previous data, the D299G TLR4
      polymorphism was not associated with risk of incident MI or stroke in this large
      prospective study of US men.

PMID- 15576654
TI  - Concurrent treatment with renin-angiotensin system blockers and acetylsalicylic
      acid reduces nuclear factor kappaB activation and C-reactive protein expression
      in human carotid artery plaques.
AB  - BACKGROUND AND PURPOSE: The local renin-angiotensin system (RAS) and
      cyclooxygenase-2 contribute to the activation of nuclear factor kappaB (NFkappaB)
      and C-reactive protein (CRP). We hypothesized that the combination of RAS
      blockers (RASb) and ASA reduces NFkappaB and CRP within atherosclerotic plaques.
      METHODS: Patients undergoing carotid endarterectomy were divided into groups
      according to treatment (RASb-acetylsalicylic acid [ASA], ASA, RASb, and control).
      The expression of NFkappaB, CRP, and CD40L was analyzed through Western blots in
      the obtained plaques. RESULTS: Plaques from patients treated with the combination
      of RASb and ASA showed lower expression of NFkappaB (25.4+/-9.8 densitometric
      units [DU]) than those of the control group (57.6+/-13.2 DU, P=0.03) as well as
      lower expression of CRP (20.9+/-9.6 DU) than those of the other treatment groups
      (ASA 86.1+/-13 DU, RASb 88.4+/-31 DU, controls 67.8+/-18.6, P=0.004). A negative
      expression of NFkappaB was associated with a reduced incidence of symptoms
      compared with a positive expression (5/33 [15.1%] versus 14/35 [40%], P=0.031).
      CONCLUSIONS: The combined treatment with RASb and ASA decreases the expression of
      inflammatory markers in atherosclerosis in humans. This study supports the role
      of the local RAS and cyclooxygenase-2 in the progression of atherosclerosis.

PMID- 15576655
TI  - Abnormal intravoxel cerebral blood flow heterogeneity in human ischemic stroke
      determined by dynamic susceptibility contrast magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: The determination of cerebral blood flow heterogeneity
      (FH) by dynamic susceptibility contrast (DSC) magnetic resonance imaging has
      recently been proposed as a tool to predict final infarct size in acute stroke.
      In this study, we describe the evolution of FH during the first week as well as
      its correlation to the patients' clinical status. METHODS: Ten patients with
      ischemic stroke were studied with DSC MRI and diffusion-weighted imaging in
      hyperacute (<6 hours) phase, at 24 hours, and 1 week after symptom onset. In
      addition to intravoxel FH, cerebral blood volume (CBV), cerebral blood flow
      (CBF), and contrast agent mean transit time (MTT) were determined from DSC MRI.
      All patients were evaluated neurologically with National Institute of Health
      Stroke Scale concurrently with the imaging sessions. RESULTS: All patients showed
      infarct growth, judged by diffusion-weighted imaging, during the week with
      simultaneous decrease in the sizes of FH, CBV, CBF, and MTT abnormalities. The FH
      abnormality was shown to be larger than CBV and CBF abnormalities at the
      hyperacute phase and 24 hours, but smaller than MTT abnormality in all 3 imaging
      sessions. The sizes of hyperacute FH, CBV, CBF, and MTT abnormalities correlated
      well with infarct size at 24 hours and at 1 week. Additionally, FH was the only
      perfusion parameter that correlated with the clinical score. CONCLUSIONS: FH
      predicts infarct size equally well with the other perfusion parameters but is
      superior in correlation with the clinical score. FH can easily be incorporated to
      hyperacute stroke imaging without additional efforts.

PMID- 15576656
TI  - Postcarotid endarterectomy hyperperfusion or reperfusion syndrome.
AB  - BACKGROUND AND PURPOSE: Hyperperfusion syndrome (HS) after carotid endarterectomy
      (CEA) has been related to impaired cerebrovascular autoregulation in a
      chronically hypoperfused hemisphere. Our aim was to provide new insight into the
      pathophysiology of the HS using magnetic resonance imaging (MRI) studies with
      diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). METHODS:
      Five out of 388 consecutive patients presented 2 to 7 days after CEA, partial
      seizures (n=5), focal deficits (n=5), and intracerebral hemorrhage (n=3). In 4
      patients, using sequential examinations, we identified vasogenic or cytotoxic
      edema by DWI; we assessed relative interhemispheric difference (RID) of cerebral
      blood flow (CBF) by PWI; and we measured middle cerebral artery mean flow
      velocities (MCA Vm) by transcranial Doppler (TCD). RESULTS: None of the patients
      presented pathological DWI hyperintensities, consistent with the absence of acute
      ischemia or cytotoxic edema. In 2 patients, we found an MRI pattern of reversible
      vasogenic edema similar to that observed in the posterior leukoencephalopathy
      syndrome. Middle cerebral artery (MCA) mean flow velocities (Vm) were not
      abnormally increased at any time. PWI documented a 20% to 44% RID of CBF in favor
      of the ipsilateral to CEA hemisphere. CONCLUSIONS: HS can occur in the presence
      of moderate relative hyperperfusion of the ipsilateral hemisphere. MCA Vm values
      may not accurately reflect RID of CBF over the cortical convexity. We suggest
      that the hemodynamic pathogenetic mechanisms of the HS are more complicated than
      hitherto believed and that they may be more accurately described by the term
      "reperfusion syndrome."

PMID- 15576657
TI  - Endothelial progenitor cells during cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Endothelial progenitor cells (EPCs) are associated with
      endothelial repair after ischemia in cardiac or peripheral circulation. There are
      no reports of EPCs with cerebrovascular disease. We present our experience with
      EPCs in patients with cerebrovascular disease. SUMMARY OF REPORT: EPC counts
      differed significantly (P<0.001) between stroke patients (acute stroke: median
      4.75 and range 0 to 33; stable stroke: median 7.25 and range 0 to 43) and control
      subjects (median 15.5 and range 4.3 to 50), independent of age. The level of EPCs
      was significantly correlated with the Framingham coronary risk score (FCRS) (rho=
      0.349; P=0.002). CONCLUSIONS: Similar to cardiac experience, the low EPC levels
      may play a role in the pathophysiology of cerebrovascular disease.

PMID- 15576658
TI  - Intermedin/adrenomedullin-2 acts within central nervous system to elevate blood
      pressure and inhibit food and water intake.
AB  - Intermedin (IMD)/adrenomedullin-2 (AM2) is a novel peptide that was independently
      discovered by two groups. The 47-amino acid peptide is homologous to
      adrenomedullin (AM) and can activate both the AM and calcitonin gene-related
      peptide (CGRP) receptors. IMD should therefore have actions similar to those of
      AM and CGRP. Indeed, like AM and CGRP, intravenous administration of IMD
      decreased blood pressure in rats and mice. We demonstrate here that
      immunoreactive IMD is present in plasma as well as heart, lung, stomach, kidney,
      pituitary, and brain. Because IMD is present in brain and both AM and CGRP have
      potent central nervous system (CNS) effects, we examined the ability of IMD
      within brain to regulate blood pressure and ingestive behaviors. Administration
      of IMD into the lateral cerebroventricle of rats caused significant, long-lasting
      elevations in mean arterial pressure and heart rate. These elevations are similar
      to the effects of CGRP and significantly greater than the effects of AM. IMD
      induced elevations in mean arterial pressure were inhibited by intravenous
      administration of phentolamine, indicating that IMD activates the sympathetic
      nervous system. Intracerebroventricular administration of IMD also inhibited food
      and water intake in sated and in food- and water-restricted animals. The effects
      on feeding are likely related to activation of the CGRP receptor and are
      independent of the effects on water intake, which are likely through the AM
      receptor. Our data indicate that IMD has potent actions within the CNS that may
      be a result of the combined activation of both AM and CGRP receptors.

PMID- 15576659
TI  - Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding
      in Siberian hamsters.
AB  - Fasting triggers many effects, including increases in circulating concentrations
      of ghrelin, a primarily stomach-derived orexigenic hormone. Exogenous ghrelin
      treatment stimulates food intake, implicating it in fasting-induced increases in
      feeding, a consummatory ingestive behavior. In Siberian hamsters, fasting also
      stimulates appetitive ingestive behaviors such as foraging and food hoarding.
      Therefore, we tested whether systemic ghrelin injections (3, 30, and 200 mg/kg)
      would stimulate these appetitive behaviors using a running wheel-based food
      delivery system coupled with simulated burrow housing. We also measured active
      ghrelin plasma concentrations after exogenous ghrelin treatment and compared them
      to those associated with fasting. Hamsters had the following: 1) no running wheel
      access, free food; 2) running wheel access, free food; or 3) foraging requirement
      (10 revolutions/pellet), no free food. Ghrelin stimulated foraging at 0-1, 2-4,
      and 4-24 h postinjection but failed to affect wheel running activity not coupled
      to food. Ghrelin stimulated food intake initially (200-350%, first 4 h) across
      all groups; however, in hamsters with a foraging requirement, ghrelin also
      stimulated food intake 4-24 h postinjection (200-250%). Ghrelin stimulated food
      hoarding 2-72 h postinjection (100-300%), most markedly 2-4 h postinjection in
      animals lacking a foraging requirement (635%). Fasting increased plasma active
      ghrelin concentrations in a time-dependent fashion, with the 3- and 30-mg/kg dose
      creating concentrations of the peptide comparable to those induced by 24-48 h of
      fasting. Collectively, these data suggest that exogenous ghrelin, similar to
      fasting, increases appetitive behaviors (foraging, hoarding) by Siberian
      hamsters, but dissimilar to fasting in this species, stimulates food intake.

PMID- 15576660
TI  - Bicarbonate secretion plays a role in chloride and water absorption of the
      European flounder intestine.
AB  - Experiments performed on isolated intestinal segments from the marine teleost
      fish, the European flounder (Platichthys flesus), revealed that the intestinal
      epithelium is capable of secondary active HCO3(-) secretion in the order of 0.2
      0.3 micromol x cm(-2) x h(-1) against apparent electrochemical gradient. The
      HCO3(-) secretion occurs via anion exchange, is dependent on mucosal Cl(-),
      results in very high mucosal HCO3(-) concentrations, and contributes
      significantly to Cl(-) and fluid absorption. This present study was conducted
      under in vivo-like conditions, with mucosal saline resembling intestinal fluids
      in vivo. These conditions result in a transepithelial potential of -16.2 mV
      (serosal side negative), which is very different from the -2.2 mV observed under
      symmetrical conditions. Under these conditions, we found a significant part of
      the HCO3(-) secretion is fueled by endogenous epithelial CO2 hydration mediated
      by carbonic anhydrase because acetazolamide (10(-4) M) was found to inhibit HCO3(
      ) secretion and removal of serosal CO(2) was found not to influence HCO3(-)
      secretion. Reversal of the epithelial electrochemical gradient for Cl(-) (removal
      of serosal Cl(-)) and elevation of serosal HCO3(-) resulted in enhanced HCO3(-)
      secretion and enhanced Cl(-) and fluid absorption. Cl(-) absorption via an anion
      exchange system appears to partly drive fluid absorption across the intestine in
      the absence of net Na(+) absorption.

PMID- 15576661
TI  - Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia.
AB  - Mu-opioid receptor activation increases body temperature and affects
      cardiovascular function. In the present study, fentanyl was administered
      intravenously [100 mug/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4
      mug (10 nmol) in 10 microl icv] in urethane-chloralose-anesthetized, artificially
      ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve
      activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8 degrees C),
      renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min)
      produced by intravenous fentanyl were abolished by premamillary transection of
      the neuraxis but were mimicked by intracerebroventricular administration of
      fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg).
      Pretreatment with the opioid antagonist naloxone (100 nmol in 10 microl icv)
      eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection
      of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus
      (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases
      in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor
      responses, and the tachycardic responses were reversed by inhibition of neurons
      in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the
      dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked
      increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These
      results indicate that activation of central mu-opioid receptors with fentanyl can
      elicit BAT thermogenesis and cardiovascular stimulation through excitation of the
      sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the
      rostral RPa and RVLM are essential for the increases in BAT thermogenesis and
      renal sympathoexcitation, respectively, induced by activation of central mu
      opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked
      hyperthermia, particularly in infants where BAT plays a significant role in
      thermoregulation.

PMID- 15576662
TI  - Energetics of high-speed running: integrating classical theory and contemporary
      observations.
AB  - We hypothesized that the anaerobic power and aerobic power outputs during all-out
      runs of any common duration between 10 and 150 s would be proportional to the
      maximum anaerobic (E(an-max)) and aerobic powers (E(aer-max)) available to the
      individual runner. Seventeen runners who differed in E(an-max) and E(aer-max) (5
      sprinters, 5 middle-distance runners, and 7 long distance runners) were tested
      during treadmill running on a 4.6 degrees incline. E(an-max) was estimated from
      the fastest treadmill speed subjects could attain for eight steps. E(aer-max) was
      determined from a progressive, discontinuous, treadmill test to failure. Oxygen
      deficits and rates of uptake were measured to assess the respective anaerobic and
      aerobic power outputs during 11-16 all-out treadmill runs that elicited failure
      between 10 and 220 s. We found that, during all-out runs of any common duration,
      the relative anaerobic and aerobic powers utilized were largely the same for
      sprint, middle-distance, and long-distance subjects. The similar fractional
      utilization of the E(an-max) and E(aer-max) available during high-speed running
      1) provides empirical values that modify and advance classic theory, 2) allows
      rates of anaerobic and aerobic energy release to be quantified from individual
      maxima and run durations, and 3) explains why the high-speed running performances
      of different event specialists can be accurately predicted (R(2) = 0.97; n = 254)
      from two direct measurements and the same exponential time constant.

PMID- 15576663
TI  - Factorial scopes of cardio-metabolic variables remain constant with changes in
      body temperature in the varanid lizard, Varanus rosenbergi.
AB  - The majority of information concerning the cardio-metabolic performance of
      varanids during exercise is limited to a few species at their preferred body
      temperature (T(b)) even though, being ectotherms, varanids naturally experience
      rather large changes in T(b). Although it is well established that absolute
      aerobic scope declines with decreasing T(b), it is not known whether changes in
      cardiac output (V(b)) and/or tissue oxygen extraction, (Ca(O2) - Cv(O2)), are in
      proportion to the rate of oxygen consumption (Vo(2)). To test this, we studied
      six Rosenberg's goannas (Varanus rosenbergi) while at rest and while maximally
      exercising on a treadmill both at 25 and 36 degrees C. During maximum exercise
      both at 25 and 36 degrees C, mass-specific rate of oxygen consumption (Vo(2kg))
      increased with an absolute scope of 8.5 ml min(-1) kg(-1) and 15.7 ml min(-1) kg(
      1), respectively. Interestingly, the factorial aerobic scope was temperature
      independent and remained at 7.0 which, at each T(b), was primarily the result of
      an increase in V(bkg), governed by approximate twofold increases both in heart
      rate (f(H)) and cardiac stroke volume (V(Skg)). Both at 25 degrees C and 36
      degrees C, the increase in V(bkg) alone was not sufficient to provide all of the
      additional oxygen required to attain maximal Vo(2kg), as indicated by a decrease
      in the blood convection requirement V(bkg)/Vo(2kg); hence, there was a
      compensatory twofold increase in (Ca(O2) - Cv(O2)). Although associated with an
      increase in hemoglobin-oxygen affinity, a decrease in T(b) did not impair
      unloading of oxygen at the tissues and act to reduce (Ca(O2) - Cv(O2)); both
      Ca(O2)) and Cv(O2)) were maintained across T(b). The change in Vo(2kg) with T(b),
      therefore, is solely reliant on the thermal dependence of V(bkg). Maintaining a
      high factorial aerobic scope across a range of T(b) confers an advantage in that
      cooler animals can achieve higher absolute aerobic scopes and presumably improved
      aerobic performance than would otherwise be achievable.

PMID- 15576664
TI  - Subfornical organ disconnection alters Fos expression in the lamina terminalis,
      supraoptic nucleus, and area postrema after intragastric hypertonic NaCl.
AB  - The lamina terminalis was severed by a horizontal knife cut through the anterior
      commissure to determine the effects of a disconnection of the subfornical organ
      (SFO) on drinking and Fos-like immunoreactivity (Fos-ir) in the rat brain in
      response to an intragastric load of hypertonic saline (5 ml/kg of 1.5 M NaCl by
      gavage). After an initial load, knife-cut rats drank significantly less water
      than sham-cut rats, thus confirming a role for the SFO in osmotic drinking. After
      a second load at least 1 wk later, the rats were not allowed to drink after the
      gavage and were perfused for analysis of Fos-ir at 90 min. Compared with sham-cut
      rats, the knife-cut rats displayed significantly elevated Fos-ir in the main body
      of the SFO, in the dorsal cap of the organum vasculosum laminae terminalis, and
      in the ventral median preoptic nucleus after the hypertonic load. The knife cut
      significantly decreased Fos-ir in the supraoptic nucleus. Fos-ir was expressed
      mainly in the midcoronal and caudal parts of the area postrema of sham-cut rats,
      and this expression was greatly reduced in knife-cut rats. These findings
      strengthen the case for the presence of independently functioning osmoreceptors
      within the SFO and suggest that the structures of the lamina terminalis provide
      mutual inhibition during hypernatremia. They also demonstrate that the Fos-ir in
      the area postrema after intragastric osmotic loading is heavily dependent on the
      intact connectivity of the SFO.

PMID- 15576665
TI  - Effects of cortisol on cardiac myocytes and on expression of cardiac genes in
      fetal sheep.
AB  - In 17 fetal sheep aged 129 days, the effects of large-dose infusions of cortisol
      (72.1 mg/day for 2-3 days) on proliferation, binucleation, and hypertrophy of
      cardiac myocytes, cardiac expression of angiotensinogen, angiotensin receptor
      subtypes 1 and 2, Glut-1, glucocorticoid and mineralocorticoid receptors,
      proteins of the MAPK pathways and calcineurin were studied. Cortisol levels were
      8.7 +/- 2.3 nM (SE) in 8 control and 1,028 +/- 189 nM in 9 treated fetuses (P <
      0.001). Cortisol had no effect on myocyte binucleation. Left ventricular free
      wall (LVFW) uni- and binucleated myocytes were larger in cortisol-treated fetuses
      (P < 0.001, P < 0.05). Cortisol-treated fetuses had higher right ventricular free
      wall (RVFW) and LVFW angiotensinogen (Aogen) mRNA levels (treated: 2.30 +/- 0.37,
      n = 8 and 2.05 +/- 0.45, n = 7 vs. control: 0.94 +/- 0.12, n = 8 and 0.67 +/-
      0.09, n = 7, P < 0.02). Levels of the glucose transporter Glut-1 mRNA were lower
      in the LVFW of treated fetuses (0.83 +/- 0.23 vs. 1.47 +/- 0.30 in control, P <
      0.05, n = 7, 8). The higher the cortisol level, the greater the Aogen mRNA level
      (RVFW, r = 0.61, P < 0.01, n = 16; LVFW, r = 0.83, P < 0.0003, n = 14). There
      were no other changes in mRNA levels nor in levels of extracellular kinase, JNK,
      p38, their phosphorylated forms, and calcineurin. Thus high levels of cortisol
      such as occur after birth do not affect fetal cardiac myocyte binucleation or
      number but are associated with higher levels of ventricular Aogen mRNA, lower
      levels of Glut-1 mRNA, and hypertrophy of LVFW myocytes. These effects could
      impact on postnatal cardiac development.

PMID- 15576666
TI  - Albumin is not an irreplaceable carrier for amphipathic mediators of
      thermoregulatory responses to LPS: compensatory role of alpha1-acid glycoprotein.
AB  - In view of the potential involvement of peripherally synthesized, circulating
      amphipathic mediators [such as platelet-activating factor (PAF) and prostaglandin
      E(2)] in the systemic inflammatory response to lipopolysaccharide (LPS), we
      hypothesized that transport of amphipaths by albumin is essential for conveying
      peripheral inflammatory signals to the brain. Our first specific aim was to test
      this hypothesis by studying LPS-induced fever and hypothermia in Nagase
      analbuminemic rats (NAR). NAR from two different colonies and normalbuminemic
      Sprague-Dawley rats were preimplanted with jugular catheters, and their febrile
      responses to a mild dose of LPS (10 microg/kg i.v.) at thermoneutrality and
      hypothermic responses to a high dose of LPS (500 microg/kg i.v.) in the cold were
      studied. NAR of both colonies developed normal febrile and hypothermic responses,
      thus suggesting that transport of amphipathic mediators by albumin is not
      indispensable for LPS signaling. Although alternative carrier proteins [such as
      alpha(1)-acid glycoprotein (AGP)] are known to assume transport functions of
      albumin in NAR, it is unknown whether inflammatory mediators are capable of
      inducing their actions when bound to alternative carriers. To test whether PAF,
      the most potent amphipathic pyrogen, causes fever when administered in an AGP
      bound form was our second aim. Sprague-Dawley rats were preimplanted with jugular
      catheters, and their thermal responses to infusion of a 1:1 [PAF-AGP] complex (40
      nmol/kg i.v.), AGP (40 nmol/kg i.v.), or various doses of free (aggregated) PAF
      were studied. The complex, but neither free PAF nor AGP, caused a high (
      approximately 1.5 degrees C) fever with a short (< 10 min) latency. This is the
      first demonstration of a pyrogenic activity of AGP-bound PAF. We conclude that,
      in the absence of albumin, AGP and possibly other carriers participate in immune
      to-brain signaling by binding and transporting amphipathic inflammatory
      mediators.

PMID- 15576667
TI  - Cardiovascular autonomic control in mice lacking angiotensin AT1a receptors.
AB  - Studies examined the role of angiotensin (ANG) AT1a receptors in cardiovascular
      autonomic control by measuring arterial pressure (AP) and heart rate (HR)
      variability and the effect of autonomic blockade in mice lacking AT1a receptors
      (AT1a -/-). Using radiotelemetry in conscious AT1a +/+ and AT1a -/- mice, we
      determined 1) AP and pulse interval (PI) variability in time and frequency
      (spectral analysis) domains, 2) AP response to alpha(1)-adrenergic and ganglionic
      blockade, and 3) intrinsic HR after ganglionic blockade. Pulsatile AP was
      recorded (5 kHz) for measurement of AP and PI and respective variability. Steady
      state AP responses to prazosin (1 microg/g ip) and hexamethonium (30 microg/g ip)
      were also measured. AP was lower in AT1a -/- vs. AT1a +/+, whereas HR was not
      changed. Prazosin and hexamethonium produced greater decreases in mean AP in AT1a
      -/- than in AT1a +/+. The blood pressure difference was marked after ganglionic
      blockade (change in mean AP of -44 +/- 10 vs. -18 +/- 2 mmHg, AT1a -/- vs. AT1a
      +/+ mice). Intrinsic HR was also lower in AT1a -/- mice (431 +/- 32 vs. 524 +/-
      22 beats/min, AT1a -/- vs. AT1a +/+). Beat-by-beat series of systolic AP and PI
      were submitted to autoregressive spectral estimation with variability quantified
      in low-frequency (LF: 0.1-1 Hz) and high-frequency (HF: 1-5 Hz) ranges. AT1a -/-
      mice showed a reduction in systolic AP LF variability (4.3 +/- 0.8 vs. 9.8 +/-
      1.3 mmHg(2)), with no change in HF (2.7 +/- 0.3 vs. 3.3 +/- 0.6 mmHg(2)). There
      was a reduction in PI variability of AT1a -/- in both LF (18.7 +/- 3.7 vs. 32.1
      +/- 4.2 ms(2)) and HF (17.7 +/- 1.9 vs. 40.3 +/- 7.3 ms(2)) ranges. The
      association of lower AP and PI variability in AT1a -/- mice with enhanced AP
      response to alpha(1)-adrenergic and ganglionic blockade suggests that removal of
      the ANG AT1a receptor produces autonomic imbalance. This is seen as enhanced
      sympathetic drive to compensate for the lack of ANG signaling.

PMID- 15576668
TI  - Developing rat lung has a sided pacemaker region for morphogenesis-related airway
      peristalsis.
AB  - Prenatal airways from diverse species are capable of spontaneous peristaltic
      contractions in each trimester. The function of this smooth muscle activity is
      unknown. We demonstrate that peristalsis of the embryonic airway originates from
      a sided pacemaker focus, is stimulated in a calcium-dependent fashion by the
      pulmonary morphogen fibroblast growth factor-10 (FGF-10), and appears coupled to
      lung growth. Airway peristalsis may be crucial for lung development (thereby
      providing a physiologic role for airway smooth muscle) and play a hitherto
      unanticipated role in reported transgenic mutant lung phenotypes.

PMID- 15576669
TI  - Identification and characterization of human pulmonary dendritic cells.
AB  - Dendritic cells (DC) are specialized antigen-presenting cells, linking innate and
      adaptive immune responses, and thus play an important role in immunologically
      mediated diseases, including pulmonary diseases such as asthma and respiratory
      viral infections. Although much is known about the characteristics of lung DC in
      animal models, very few data concerning human lung DC are available. The goal of
      our study was to identify and characterize dendritic cells in human lung by
      preparing single-cell suspensions from surgical resection specimens and
      subsequent labeling with the recently developed blood dendritic cell antigen
      (BDCA) markers. A straightforward isolation procedure was developed to avoid
      phenotypical and functional changes induced by extensive purification methods. In
      this way, human lung DC were directly identified without the need for an
      additional adherence step for further purification. For the first time, we
      demonstrate the presence of three previously unidentified DC subsets in human
      lung digests: myeloid DC type 1 (BDCA1+/HLA-DR+), myeloid DC type 2 (BDCA3+/HLA
      DR+), and plasmacytoid DC (BDCA2+/CD123+). The presence of CD1a+ DC in the human
      lung was confirmed. The identification and characterization of different human
      pulmonary DC subtypes is of great importance for the future development of DC
      based immunotherapies.

PMID- 15576670
TI  - German cockroach proteases regulate interleukin-8 expression via nuclear factor
      for interleukin-6 in human bronchial epithelial cells.
AB  - German cockroach extract synergistically regulates tumor necrosis factor-alpha
      (TNF-alpha)-induced interleukin (IL)-8 expression in human airway epithelial
      cells. The IL-8 promoter contains nuclear factor (NF)-kappaB, activating protein
      (AP)-1, and NF for IL-6 (NF-IL6) transcription factor binding regions. Because
      cockroach extract activates extracellular regulated kinase (ERK), a known
      activator of AP-1 and NF-IL6, we focused on the regulation of these transcription
      factors. Although TNF-alpha and cockroach extract both increased AP-1
      translocation, mutation of the AP-1 site in the context of the wild-type promoter
      had no effect on cockroach extract-induced synergy. Mutation of the NF-IL6 site
      in the context of the wild-type IL-8 promoter, or overexpression of a dominant
      negative NF-IL6 mutant, each abolished cockroach extract-induced synergy.
      Cockroach extract induced NF-IL6 translocation and DNA binding, an effect that
      was further increased in the presence of TNF-alpha. Cockroach extract-induced
      regulation of NF-IL6 was due to active serine proteases in the extract as well as
      activation of protease activated receptor (PAR)-2, but not PAR-1. Chemical
      inhibition of ERK also attenuated cockroach extract-induced NF-IL6-DNA binding.
      We conclude that proteases in German cockroach extract regulate PAR-2 and ERK to
      increase NF-IL6 activity and synergistically regulate TNF-alpha-induced IL-8
      promoter activity in human airway epithelium.

PMID- 15576671
TI  - Embryonic stem cells generate airway epithelial tissue.
AB  - Embryonic stem (ES) cells are self-renewable and pluripotent cells derived from
      the inner cell mass of a blastocyst-stage embryo. ES cell pluripotency is being
      investigated increasingly to obtain specific cell lineages for therapeutic
      treatments and tissue engineering. Type II alveolar epithelial cells have been
      derived from murine ES cells, but the capacity of the latter to generate
      differentiated airway epithelial tissue has never been reported. Herein, we show
      by RT-PCR and immunocytochemistry that murine ES cells are able to differentiate
      into nonciliated secretory Clara cells, and that type I collagen induces this
      commitment. Moreover, when cultured at the air-liquid interface, ES cells give
      rise to a fully differentiated airway epithelium. By quantitative histologic
      examination, immunohistochemistry, and scanning electron microscopy, we show that
      the bioengineered epithelium is composed of basal, ciliated, intermediate, and
      Clara cells, similar to those of native tracheobronchial airway epithelium.
      Transmission electron microscopy and Western blotting reveal that the generated
      epithelium also exhibits the ultrastructural features and secretory functions
      characteristic of airway epithelial tissue. These results open new perspectives
      for cell therapy of injured epithelium in airway diseases, such as
      bronchopulmonary dysplasia, cystic fibrosis, or bronchiolitis obliterans.

PMID- 15576672
TI  - Toll-like receptor 4 or 2 agonists decrease allergic inflammation.
AB  - Toll-like receptors (TLRs) recognize highly conserved microbial molecular
      patterns, such as found in endotoxin. This study tested whether TLR4 and TLR2
      stimulation in vivo would modulate subsequent adaptive (allergic) immune
      responses. We analyzed the effects of pulmonary administration of a TLR4 agonist,
      lipid A (LpA), and two TLR2 agonists, peptidoglycan (Ppg) and PamCys, in a murine
      model of allergic inflammation. The TLR agonists were administered during
      allergen sensitization or challenge. Both TLR agonists decreased the allergen
      induced pulmonary recruitment of eosinophils when administered at sensitization
      or challenge. When given before sensitization, the TLR4 and TLR2 agonists
      decreased additional allergen-induced parameters of inflammation (pulmonary
      eosinophilia, bronchoalveolar lavage IL-13, total serum IgE, and airway
      hyperresponsiveness). Interestingly, TLR4 and TLR2 agonists decreased the number
      of CD4+ cells in the lung. Also, at the site of local allergen stimulation, the
      draining thoracic lymph nodes, allergen-induced lymphocyte proliferation, and IL
      13 secretion were decreased by administration of LpA and Ppg. These data provide
      a distinct example of the modulation of adaptive (allergic) responses by non
      antigen-dependent stimuli. Our findings also demonstrate that both TLR4 and TLR2
      agonists decrease allergic responses, supporting the concept that exposure to
      bacterial components under defined conditions may protect against allergic
      disease.

PMID- 15576673
TI  - A multi-enzyme model for Pyrosequencing.
AB  - Pyrosequencing is a DNA sequencing technique based on sequencing-by-synthesis
      enabling rapid real-time sequence determination. This technique employs four
      enzymatic reactions in a single tube to monitor DNA synthesis. Nucleotides are
      added iteratively to the reaction and in case of incorporation, pyrophosphate
      (PPi) is released. PPi triggers a series of reactions resulting in production of
      light, which is proportional to the amount of DNA and number of incorporated
      nucleotides. Generated light is detected and recorded by a detector system in the
      form of a peak signal, which reflects the activity of all four enzymes in the
      reaction. We have developed simulations to model the kinetics of the enzymes.
      These simulations provide a full model for the Pyrosequencing four-enzyme system,
      based on which the peak height and shape can be predicted depending on the
      concentrations of enzymes and substrates. Simulation results are shown to be
      compatible with experimental data. Based on these simulations, the rate-limiting
      steps in the chain can be determined, and K(M) and kcat of all four enzymes in
      Pyrosequencing can be calculated.

PMID- 15576674
TI  - Rapid analysis of CpG methylation patterns using RNase T1 cleavage and MALDI-TOF.
AB  - Here, we introduce a method for the fast and accurate analysis of DNA methylation
      based on bisulfite-treated DNA. The target region is PCR amplified using a T7 RNA
      polymerase promoter-tagged primer. A subsequent in vitro transcription leads to a
      transcript which contains guanosine residues only at sites that contained
      methylated cytosines before bisulfite treatment. In a single tube reaction using
      guanosine-specific cleavage by RNase T1, a specific pattern of RNA fragments is
      formed. This pattern directly represents the methylation state of the sample DNA
      and is analyzed using matrix-assisted laser desorption ionization time-of-flight
      technology. This method was successfully applied to the analysis of artificially
      methylated and unmethylated DNA, mixtures thereof and colon DNA samples. The
      applicability for the analysis of both PCR products and cloned PCR products is
      demonstrated. The observed methylation patterns were confirmed by bisulfite
      sequencing.

PMID- 15576675
TI  - MethylQuant: a sensitive method for quantifying methylation of specific cytosines
      within the genome.
AB  - Here we present MethylQuant, a novel method that allows accurate quantification
      of the methylation level of a specific cytosine within a complex genome. This
      method relies on the well-established treatment of genomic DNA with sodium
      bisulfite, which converts cytosine into uracil without modifying 5-methyl
      cytosine. The region of interest is then PCR-amplified and quantification of the
      methylation status of a specific cytosine is performed by methylation-specific
      real-time PCR with SYBR Green I using one of the primers whose 3' end
      discriminates between the methylation states of this cytosine. The presence of a
      locked nucleic acid at the 3' end of the discriminative primer provides the
      specificity necessary for accurate and sensitive quantification, even when one of
      the methylation states is present at a level as low as 1% of the overall
      population. We demonstrate that accurate quantification of the methylation status
      of specific cytosines can be achieved in biological samples. The method is high
      throughput, cost-effective, relatively simple and does not require any specific
      equipment other than a real-time PCR instrument.

PMID- 15576676
TI  - In vitro selection of Jun-associated proteins using mRNA display.
AB  - Although yeast two-hybrid assay and biochemical methods combined with mass
      spectrometry have been successfully employed for the analyses of protein-protein
      interactions in the field of proteomics, these methods encounter various
      difficulties arising from the usage of living cells, including inability to
      analyze toxic proteins and restriction of testable interaction conditions.
      Totally in vitro display technologies such as ribosome display and mRNA display
      are expected to circumvent these difficulties. In this study, we applied an mRNA
      display technique to screening for interactions of a basic leucine zipper domain
      of Jun protein in a mouse brain cDNA library. By performing iterative affinity
      selection and sequence analyses, we selected 16 novel Jun-associated protein
      candidates in addition to four known interactors. By means of real-time PCR and
      pull-down assay, 10 of the 16 newly discovered candidates were confirmed to be
      direct interactors with Jun in vitro. Furthermore, interaction of 6 of the 10
      proteins with Jun was observed in cultured cells by means of co
      immunoprecipitation and observation of subcellular localization. These results
      demonstrate that this in vitro display technology is effective for the discovery
      of novel protein-protein interactions and can contribute to the comprehensive
      mapping of protein-protein interactions.

PMID- 15576677
TI  - Quantitative detection of siRNA and single-stranded oligonucleotides:
      relationship between uptake and biological activity of siRNA.
AB  - The quantitative detection of oligomeric nucleic acids including short double
      stranded RNA in cells and tissues becomes increasingly important. Here, we
      describe a method for the detection of siRNA in extracts prepared from mammalian
      cells, which is based on liquid hybridization with a 32P-labelled probe followed
      by a nuclease protection step. The limit of detection of absolute amounts of
      siRNA is in the order of 10-100 amol. This methodology is suited to
      quantitatively follow the spontaneous uptake of siRNA by mammalian cells, i.e.
      without the use of carrier substances. This protocol may also be used to detect
      extremely low amounts of other kinds of short nucleic acids, including antisense
      oligonucleotides.

PMID- 15576678
TI  - RNA silencing in plants by the expression of siRNA duplexes.
AB  - In animal cells, stable RNA silencing can be achieved by vector-based small
      interfering RNA (siRNA) expression system, in which Pol III RNA gene promoters
      are used to drive the expression of short hairpin RNA, however, this has not been
      demonstrated in plants. Whether Pol III RNA gene promoter is capable of driving
      siRNA expression in plants is unknown. Here, we report that RNA silencing was
      achieved in plants through stable expression of short hairpin RNA, which was
      driven by Pol III RNA gene promoters. Using glucuronidase (GUS) transformed
      tobacco as a model system, the results demonstrated that 21 nt RNA duplexes,
      targeting at different sites of GUS gene, were stably expressed under the control
      of either human H1 or Arabidopsis 7SL RNA gene promoter, and GUS gene was
      silenced in 80% of siRNA transgenics. The severity of silencing was correlated
      with the abundance of siRNA expression but independent of the target sites and
      uridine residue structures in siRNA hairpin transcripts. Thus, the specific
      expression of siRNA provides a new system for the study of siRNA silencing
      pathways and functional genomics in plants. Moreover, the effectiveness of the
      human H1 promoter in a plant background suggested a conserved mechanism
      underlying Pol III complex functionality.

PMID- 15576679
TI  - Identification of genes with fast-evolving regions in microbial genomes.
AB  - Complete sequences of multiple strains of the same microbial species provide an
      invaluable source for studying the evolutionary dynamics between orthologous
      genes over a relatively short time scale. Usually the intensity of the selection
      pressure is inferred from a comparison between the nonsynonymous substitution
      rate and the synonymous substitution rate. In this paper, we propose an
      alternative method for detecting genes with one or more fast-evolving regions
      from pairwise comparisons of orthologous genes. Our method looks for regions with
      overrepresented nonsynonymous mutations along the alignment, and requires a
      higher nonsynonymous evolution rate in those regions than the neutral evolution
      rate. It identifies gene targets under intensive selection pressure that are not
      detected from the conventional rate comparison analysis. For those identified
      genes with known annotations, most of them have a clear role in processes such as
      bacterial defense and host-pathogen interactions. Gene sets reported from our
      method provide a measure of the phenotypic divergence between two closely related
      genomes.

PMID- 15576680
TI  - Change of RNase P RNA function by single base mutation correlates with
      perturbation of metal ion binding in P4 as determined by NMR spectroscopy.
AB  - The solution structures of two 27 nt RNA hairpins and their complexes with
      cobalt(III)-hexammine [Co(NH(3))(6)(3+)] were determined by NMR spectroscopy. The
      RNA hairpins are variants of the P4 region from Escherichia coli RNase P RNA: a U
      to-A mutant changing the identity of the bulged nucleotide, and a U-to-C, C-to-U
      double mutant changing only the bulge position. Structures calculated from NMR
      constraints show that the RNA hairpins adopt different conformations. In the U-to
      C, C-to-U double mutant, the conserved bulged uridine in the P4 wild-type stem is
      found to be shifted in the 3'-direction by one nucleotide when compared with the
      wild-type structure. Co(NH(3))(6)(3+) is used as a spectroscopic probe for
      Mg(H(2)O)(6)(2+) binding sites because both complexes have octahedral symmetry
      and have similar radii. Intermolecular NOE crosspeaks between Co(NH(3))(6)(3+)
      and RNA protons were used to locate the site of Co(NH(3))(6)(3+) binding to both
      RNA hairpins. The metal ion binds in the major groove near a bulge loop in both
      mutants, but is shifted 3' by about one base pair in the double mutant. The
      change of the metal ion binding site is compared with results obtained on
      corresponding mutant RNase P RNA molecules as reported by Harris and co-workers
      (RNA, 1, 210-218).

PMID- 15576681
TI  - Genetics of lagging strand DNA synthesis and maturation in fission yeast:
      suppression analysis links the Dna2-Cdc24 complex to DNA polymerase delta.
AB  - The Cdc24 protein is essential for the completion of chromosomal DNA replication
      in fission yeast. Although its precise role in this process is unclear, Cdc24
      forms a complex with Dna2, a conserved endonuclease-helicase implicated in the
      removal of the RNA-DNA primer during Okazaki fragment processing. To gain further
      insights into Cdc24-Dna2 function, we screened for chromosomal suppressors of the
      temperature-sensitive cdc24-M38 allele and mapped the suppressing mutations into
      six complementation groups. Two of these mutations defined genes encoding the
      Pol3 and Cdc27 subunits of DNA polymerase delta. Sequence analysis revealed that
      all the suppressing mutations in Cdc27 resulted in truncation of the protein and
      loss of sequences that included the conserved C-terminal PCNA binding motif,
      previously shown to play an important role in maximizing enzyme processivity in
      vitro. Deletion of this motif is shown to be sufficient for suppression of both
      cdc24-M38 and dna2-C2, a temperature-sensitive allele of dna2(+), suggesting that
      disruption of the interaction between Cdc27 and PCNA renders the activity of the
      Cdc24-Dna2 complex dispensable.

PMID- 15576682
TI  - PriA helicase and SSB interact physically and functionally.
AB  - PriA helicase is the major DNA replication restart initiator in Escherichia coli
      and acts to reload the replicative helicase DnaB back onto the chromosome at
      repaired replication forks and D-loops formed by recombination. We have
      discovered that PriA-catalysed unwinding of branched DNA substrates is stimulated
      specifically by contact with the single-strand DNA binding protein of E.coli,
      SSB. This stimulation requires binding of SSB to the initial DNA substrate and is
      effected via a physical interaction between PriA and the C-terminus of SSB.
      Stimulation of PriA by the SSB C-terminus may act to ensure that efficient PriA
      catalysed reloading of DnaB occurs only onto the lagging strand template of
      repaired forks and D-loops. Correlation between the DNA repair and recombination
      defects of strains harbouring an SSB C-terminal mutation with inhibition of this
      SSB-PriA interaction in vitro suggests that SSB plays a critical role in
      facilitating PriA-directed replication restart. Taken together with previous
      data, these findings indicate that protein-protein interactions involving SSB may
      coordinate replication fork reloading from start to finish.

PMID- 15576684
TI  - Organisations and safety in health care.

PMID- 15576683
TI  - Evolution of dnmt-2 and mbd-2-like genes in the free-living nematodes
      Pristionchus pacificus, Caenorhabditis elegans and Caenorhabditis briggsae.
AB  - Whole genome sequencing of several metazoan model organisms provides a platform
      for studying genome evolution. How representative are the genomes of these model
      organisms for their respective phyla? Within nematodes, for example, the free
      living soil nematode Caenorhabditis elegans is a highly derived species with
      unusual genomic characters, such as a reduced Hox cluster (Curr. Biol., 13, 37
      40) and the absence of a Hedgehog signaling system. Here, we describe the recent
      loss of a DNA methyltransferase-2 gene (dnmt-2) in C.elegans. A dnmt-2-like gene
      is present in the satellite model organism Pristionchus pacificus, another free
      living nematode that diverged from C.elegans 200-300 million years ago. In
      contrast, C.elegans, Caenorhabditis briggsae and P.pacificus all contain an mbd-2
      like gene, which encodes another essential component of the methylation system of
      higher animals and fungi. Cel-mbd-2 is expressed throughout development and RNA
      interference (RNAi) experiments result in variable phenotypes. In contrast, Cbr
      mbd-2 RNAi results in paralyzed larval or adult worms suggesting recent changes
      of gene function within the genus Caenorhabditis. We speculate that both genes
      were part of an ancestral DNA methylation system in nematodes and that gene loss
      and sequence divergence have abolished DNA methylation in C.elegans.

PMID- 15576685
TI  - Unlearning in health care.
AB  - Learning in health care is essential if healthcare organisations are to tackle a
      challenging quality of care agenda. Yet while we know a reasonable amount about
      the nature of learning, how learning occurs, the forms it can take, and the
      routines that encourage it to happen within organisations, we know very little
      about the nature and processes of unlearning. We review the literature addressing
      issues pivotal to unlearning (what it is, why it is important, and why it is
      often neglected), and go further to explore the conditions under which unlearning
      is likely to be encouraged. There is a difference between routine unlearning (and
      subsequent re-learning) and deep unlearning--unlearning that requires a
      substantive break with previous modes of understanding, doing, and being. We
      argue that routine unlearning merely requires the establishment of new habits,
      whereas deep unlearning is a sudden, potentially painful, confrontation of the
      inadequacy in our substantive view of the world and our capacity to cope with
      that world competently.

PMID- 15576686
TI  - Redirecting traditional professional values to support safety: changing
      organisational culture in health care.
AB  - Professionals in healthcare organisations who seek to enhance safety and quality
      in an increasingly demanding industry environment often identify culture as a
      barrier to change. The cultural focus on individual autonomy, for example, seems
      to conflict with desired norms of teamwork, problem reporting, and learning. We
      offer a definition and explication of why culture is important to change efforts.
      A cultural analysis of health care suggests professional values that can be
      redirected to support change. We offer examples of organisations that drew upon
      cultural strengths to create new ways of working and gradually shifted the
      culture.

PMID- 15576687
TI  - A typology of organisational cultures.
AB  - There is wide belief that organisational culture shapes many aspects of
      performance, including safety. Yet proof of this relationship in a medical
      context is hard to find. In contrast to human factors, whose contributions are
      many and notable, culture's impact remains a common-sense, rather than a
      scientific, concept. The objectives of this paper are to show that organisational
      culture bears a predictive relationship with safety and that particular kinds of
      organisational culture improve safety, and to develop a typology predictive of
      safety performance. Because information flow is both influential and also
      indicative of other aspects of culture, it can be used to predict how
      organisations or parts of them will behave when signs of trouble arise. From case
      studies and some systematic research it appears that information culture is
      indeed associated with error reporting and with performance, including safety.
      Yet this relationship between culture and safety requires more exploration before
      the connection can be considered definitive.

PMID- 15576688
TI  - Beyond the organisational accident: the need for "error wisdom" on the frontline.
AB  - Complex, well defended, high technology systems are subject to rare but usually
      catastrophic organisational accidents in which a variety of contributing factors
      combine to breach the many barriers and safeguards. To the extent that healthcare
      institutions share these properties, they too are subject to organisational
      accidents. A detailed case study of such an accident is described. However, it is
      important to recognise that health care possesses a number of characteristics
      that set it apart from other hazardous domains. These include the diversity of
      activity and equipment, a high degree of uncertainty, the vulnerability of
      patients, and a one to one or few to one mode of delivery. Those in direct
      contact with patients, particularly nurses and junior doctors, often have little
      opportunity to reform the system's defences. It is argued that some
      organisational accident sequences could be thwarted at the last minute if those
      on the frontline had acquired some degree of error wisdom. Some mental skills are
      outlined that could alert junior doctors and nurses to situations likely to
      promote damaging errors.

PMID- 15576689
TI  - Learning from failure in health care: frequent opportunities, pervasive barriers.
AB  - The notion that hospitals and medical practices should learn from failures, both
      their own and others', has obvious appeal. Yet, healthcare organisations that
      systematically and effectively learn from the failures that occur in the care
      delivery process, especially from small mistakes and problems rather than from
      consequential adverse events, are rare. This article explores pervasive barriers
      embedded in healthcare's organisational systems that make shared or
      organisational learning from failure difficult and then recommends strategies for
      overcoming these barriers to learning from failure, emphasising the critical role
      of leadership. Firstly, leaders must create a compelling vision that motivates
      and communicates urgency for change; secondly, leaders must work to create an
      environment of psychological safety that fosters open reporting, active
      questioning, and frequent sharing of insights and concerns; and thirdly, case
      study research on one hospital's organisational learning initiative suggests that
      leaders can empower and support team learning throughout their organisations as a
      way of identifying, analysing, and removing hazards that threaten patient safety.

PMID- 15576690
TI  - Integrating patient safety into the clinical microsystem.
AB  - Healthcare institutions continue to face challenges in providing safe patient
      care in increasingly complex organisational and regulatory environments while
      striving to maintain financial viability. The clinical microsystem provides a
      conceptual and practical framework for approaching organisational learning and
      delivery of care. Tensions exist between the conceptual theory and the daily
      practical applications of providing safe and effective care within healthcare
      systems. Healthcare organisations are often complex, disorganised, and opaque
      systems to their users and their patients. This disorganisation may lead to
      patient discomfort and harm as well as much waste. Healthcare organisations are
      in some sense conglomerates of smaller systems, not coherent monolithic
      organisations. The microsystem unit allows organisational leaders to embed
      quality and safety into a microsystem's developmental journey. Leaders can set
      the stage for making safety a priority for the organisation while allowing
      individual microsystems to create innovative strategies for improvement.

PMID- 15576691
TI  - General attributes of safe organisations.
AB  - In analysing the safety strategies of organisations successfully managing
      hazardous systems it is apparent that safety itself is a problematic, and even
      risky, concept. It is less the valuation of safety per se than the disvalue
      surrounding mis-specification, misidentification, and misunderstanding that
      drives reliability in these organisations. Two contrasting models of high
      reliability can be identified in precluded event and resilience focused
      organisations. Each model is adapted to different properties in the raw material,
      process variances, and knowledge base of the organisation. These two models bound
      the reliability approaches available to medicine. The implications of each for
      medical reliability strategy are explored, and the possible adaptation of
      features from each for medical organisations are assessed.

PMID- 15576692
TI  - Leadership for safety: industrial experience.
AB  - The importance of leadership for effective safety management has been the focus
      of research attention in industry for a number of years, especially in energy and
      manufacturing sectors. In contrast, very little research into leadership and
      safety has been carried out in medical settings. A selective review of the
      industrial safety literature for leadership research with possible application in
      health care was undertaken. Emerging findings show the importance of
      participative, transformational styles for safety performance at all levels of
      management. Transactional styles with attention to monitoring and reinforcement
      of workers' safety behaviours have been shown to be effective at the supervisory
      level. Middle managers need to be involved in safety and foster open
      communication, while ensuring compliance with safety systems. They should allow
      supervisors a degree of autonomy for safety initiatives. Senior managers have a
      prime influence on the organisation's safety culture. They need to continuously
      demonstrate a visible commitment to safety, best indicated by the time they
      devote to safety matters.

PMID- 15576693
TI  - Implications for practice: challenges for healthcare leaders in fostering patient
      safety.
AB  - Although various government and regulatory organisations have identified
      practices that may enhance patient safety, there is little empirical or
      theoretical research to inform the decisions of healthcare leaders seeking to
      create patient safety programmes within their hospitals and clinics. In order to
      understand the challenges facing hospital and health system executives, we
      describe the experience of the Executive Session on Patient Safety. The
      executives identified five major problems in leading patient safety: 1) how
      should executives structure their organisations to deliver safe care? 2) how
      should executives monitor and measure their organisation's safety performance? 3)
      how should executives spread and sustain patient safety innovation? 4) how should
      executives manage the relationship with the external environment? and 5) how
      should executives manage their own behaviour in order to lead for safety? The
      organisational infrastructure needed for safer care is being developed by
      practitioners out in the field as a matter of necessity. Strengthening the
      scientific basis for organisational leadership in patient safety is a vital but
      neglected area of study.

PMID- 15576694
TI  - The clinician, the patient and the organisation: a crucial three sided
      relationship.

PMID- 15576695
TI  - The improvement horse race: bet on the UK.

PMID- 15576696
TI  - Challenges for an international guidelines collaboration.

PMID- 15576697
TI  - "Role drift" to unlicensed assistants: risks to quality and safety.

PMID- 15576698
TI  - Researching doctors' decisions.

PMID- 15576699
TI  - Are simulation and didactic crisis resource management (CRM) training
      synergistic?

PMID- 15576700
TI  - Informed consent: don't throw out the moral baby with the critical bath water.

PMID- 15576701
TI  - The consultation game.

PMID- 15576702
TI  - Simulation based teamwork training for emergency department staff: does it
      improve clinical team performance when added to an existing didactic teamwork
      curriculum?
AB  - OBJECTIVE: To determine if high fidelity simulation based team training can
      improve clinical team performance when added to an existing didactic teamwork
      curriculum. SETTING: Level 1 trauma center and academic emergency medicine
      training program. PARTICIPANTS: Emergency department (ED) staff including nurses,
      technicians, emergency medicine residents, and attending physicians.
      INTERVENTION: ED staff who had recently received didactic training in the
      Emergency Team Coordination Course (ETCC) also received an 8 hour intensive
      experience in an ED simulator in which three scenarios of graduated difficulty
      were encountered. A comparison group, also ETCC trained, was assigned to work
      together in the ED for one 8 hour shift. Experimental and comparison teams were
      observed in the ED before and after the intervention. DESIGN: Single, crossover,
      prospective, blinded and controlled observational study. Teamwork ratings using
      previously validated behaviorally anchored rating scales (BARS) were completed by
      outside trained observers in the ED. Observers were blinded to the identification
      of the teams. RESULTS: There were no significant differences between experimental
      and comparison groups at baseline. The experimental team showed a trend towards
      improvement in the quality of team behavior (p = 0.07); the comparison group
      showed no change in team behavior during the two observation periods (p = 0.55).
      Members of the experimental team rated simulation based training as a useful
      educational method. CONCLUSION: High fidelity medical simulation appears to be a
      promising method for enhancing didactic teamwork training. This approach, using a
      number of patients, is more representative of clinical care and is therefore the
      proper paradigm in which to perform teamwork training. It is, however, unclear
      how much simulator based training must augment didactic teamwork training for
      clinically meaningful differences to become apparent.

PMID- 15576703
TI  - Women's accounts of consenting to surgery: is consent a quality problem?
AB  - BACKGROUND: Consent has been placed at the centre of doctor-patient
      relationships. Attempts to improve the consent process in medicine have drawn on
      bioethical and legal traditions. Current approaches to consent emphasise the
      provision of information and have, in the UK, resulted in a single standardised
      format and process for both elective and emergency situations. Investigation of
      patients' perceptions and priorities are important in understanding the quality
      of the consent process. METHODS: In this qualitative study, semi-structured
      interviews were conducted with 25 women. Eleven had elective and 14 had emergency
      operations in obstetrics and gynaecology. All interviews were recorded and
      transcribed verbatim. Data analysis was based on the constant comparative method.
      RESULTS: Participants' perceptions of surgery strongly influenced the meanings
      they gave to consent. Some, particularly those undergoing elective operations,
      wanted surgery. Others were uncertain of their desire for surgery or felt that it
      was imposed on them. Consenting was interpreted as a ritualistic legal procedure.
      There was an overwhelming tendency to view consent as not primarily serving
      patients' needs, although some advantages of the consent process were identified.
      Accounts made no reference to ethics. CONCLUSION: Countering paternalism will
      remain difficult to achieve if issues surrounding consent continue to be debated
      between professionals without due effort to reflect patients' own views and
      values and to appreciate the circumstances under which consent is sought.

PMID- 15576704
TI  - How do stakeholder groups vary in a Delphi technique about primary mental health
      care and what factors influence their ratings?
AB  - BACKGROUND: While mental health is a core part of primary care, there are few
      validated quality measures and little relevant internationally published
      research. Consensus panel methods are a useful means of developing quality
      measures where evidence is sparse and/or opinions are diverse. However, little is
      known about the dynamics of consensus techniques and the factors that influence
      the judgements and ratings of panels and individual panelists. OBJECTIVES: (1) To
      describe differences in panel ratings on the quality of primary mental health
      care services by patient, carer, professional and managerial panels within a
      Delphi procedure; and (2) to explore why different panels and panelists rate
      quality indicators of primary mental health care differently. DESIGN: Two round
      postal Delphi technique and exploratory semi-structured interviews. PARTICIPANTS:
      115 panelists across 11 panels. Eleven panelists were subsequently interviewed.
      RESULTS: 87 of 334 indicators (26%) were rated face valid by all 11 panels. There
      was little disagreement within panel ratings but significant differences between
      panels. The GP panel rated the least number of indicators valid (n = 138, 41%)
      and carers the most (n = 304, 91%). The way in which panelists interpreted and
      conceptualised the indicators and their definition of quality of mental health
      care affected the way in which participants made their ratings. CONCLUSIONS:
      Stakeholders in primary mental health care have diverse views of quality of care
      and these differences translate into how they rate quality indicators.
      Exploratory interviews suggest that ratings are influenced by past experience,
      expectations, definitions of quality of care, and perceived power relationships
      between stakeholders.

PMID- 15576705
TI  - Towards primary care for non-serious 999 callers: results of a controlled study
      of "Treat and Refer" protocols for ambulance crews.
AB  - OBJECTIVE: To develop and evaluate "Treat and Refer" protocols for ambulance
      crews, allowing them to leave patients at the scene with onward referral or self
      care advice as appropriate. METHODS: Crew members from one ambulance station were
      trained to use the treatment protocols. Processes and outcomes of care for
      patients attended by trained crews were compared with similar patients attended
      by crews from a neighbouring station. Pre-hospital records were collected for all
      patients. Records of any emergency department and primary care contacts during
      the 14 days following the call were collected for non-conveyed patients who were
      also followed up by postal questionnaire. RESULTS: Twenty three protocols were
      developed which were expected to cover over 75% of patients left at the scene by
      the attending crew. There were 251 patients in the intervention arm and 537 in
      the control arm. The two groups were similar in terms of age, sex and condition
      category but intervention cases were more likely to have been attended during
      daytime hours than at night. There was no difference in the proportion of
      patients left at the scene in the intervention and control arms; the median job
      cycle time was longer for intervention group patients. Protocols were reported as
      having been used in 101 patients (40.2%) in the intervention group; 17 of the
      protocols were recorded as having been used at least once during the study.
      Clinical documentation was generally higher in the intervention group, although a
      similar proportion of patients in both groups had no clinical assessments
      recorded. 288 patients were left at the scene (93 in the intervention group, 195
      in the control group). After excluding those who refused to travel, there were
      three non-conveyed patients in each group who were admitted to hospital within 14
      days of the call who were judged to have been left at home inappropriately. A
      higher proportion of patients in the intervention arm reported satisfaction with
      the service and advice provided. CONCLUSIONS: "Treat and Refer" protocols did not
      increase the number of patients left at home but were used by crews and were
      acceptable to patients. The protocols increased job cycle time and some safety
      issues were identified. Their introduction is complex, and the extent to which
      the content of the protocols, decision support and training can be refined needs
      further study.

PMID- 15576707
TI  - Designing information technology to support prescribing decision making.
AB  - The use of computerised prescribing and decision support to reduce medication
      error is a common element of medication safety policy. This paper discusses the
      sort of characteristics that a decision support system should have. The system
      should slot into a wider vision of good prescribing, not conflict with it, and
      should be based on our understanding of the causes of error. As yet there is
      little evidence that decision support is effective in changing patient outcome,
      and the evaluation in this field is of limited quality and generalisability. It
      is proposed that software design should target high risk patients and drugs, trap
      dosing errors, have standardised methods of production and evaluation, be
      congruent with good prescribing, focus on the tasks that computers do well,
      individualise treatment, and ensure that prescribers enjoy using the final
      product.

PMID- 15576708
TI  - Improving the quality of health care: using international collaboration to inform
      guideline programmes by founding the Guidelines International Network (G-I-N).
AB  - Clinical practice guidelines are regarded as powerful tools to achieve effective
      health care. Although many countries have built up experience in the development,
      appraisal, and implementation of guidelines, until recently there has been no
      established forum for collaboration at an international level. As a result, in
      different countries seeking similar goals and using similar strategies, efforts
      have been unnecessarily duplicated and opportunities for harmonisation lost
      because of the lack of a supporting organisational framework. This triggered a
      proposal in 2001 for an international guidelines network built on existing
      partnerships. A baseline survey confirmed a strong demand for such an entity. A
      multinational group of guideline experts initiated the development of a non
      profit organisation aimed at promotion of systematic guideline development and
      implementation. The Guidelines International Network (G-I-N) was founded in
      November 2002. One year later the Network released the International Guideline
      Library, a searchable database which now contains more than 2000 guideline
      resources including published guidelines, guidelines under development,
      "guidelines for guidelines", training materials, and patient information tools.
      By June 2004, 52 organisations from 27 countries had joined the network including
      institutions from Oceania, North America, and Europe, and WHO. This paper
      describes the process that led to the foundation of the G-I-N, its
      characteristics, prime activities, and ideas on future projects and
      collaboration.

PMID- 15576709
TI  - Models of the medical consultation: opportunities and limitations of a game
      theory perspective.
AB  - The medical consultation is best understood as a two-way social interaction
      involving interactive decision making. Game theory--a theory based on assumptions
      of rational choice and focusing on interactive decision making--has the potential
      to provide models of the consultation that can be used to generate empirically
      testable predictions about the factors that promote quality of care. Three
      different game structures--the Prisoner's Dilemma game, the Assurance game, and
      the Centipede game--all provide insights into the possible underlying dynamics of
      the doctor-patient interaction. Further empirical work is needed to uncover the
      underlying game structures that occur most commonly in medical consultations.
      Game theory has the potential to provide a new conceptual and theoretical basis
      for future empirical work on the interaction between doctors and their patients.

PMID- 15576710
TI  - Surgical fires: perioperative communication is essential to prevent this rare but
      devastating complication.
AB  - A fire on or within a surgical patient is a continuing risk in modern surgery.
      Unfortunately, the sensitivity of surgical and anaesthesia staff to this hazard
      has waned over the past 25 years with cessation of the use of flammable
      anaesthetic agents. Prevention of surgical fires requires understanding the risks
      and effective communication between surgical, anaesthesia, and operating nursing
      staffs. Preventive measures exist but have yet to diffuse sufficiently across
      professional boundaries. Based on a review of relevant databases, decades of
      experience from field investigations, and a review of the medical literature,
      this paper discusses the incidence of surgical fires, the responsibility for
      prevention in the perioperative setting, and the procedures for surgical fire
      prevention and extinguishment.

PMID- 15576711
TI  - Avedis Donabedian: father of quality assurance and poet.

PMID- 15576712
TI  - Mobile communication regulations updated: how safely are doctors' telephones
      used?

PMID- 15576714
TI  - Non-specific "non-effects" of vaccination.

PMID- 15576715
TI  - Suicide pacts and the internet.

PMID- 15576716
TI  - Benign parotid tumours.

PMID- 15576717
TI  - Managing osteoarthritis of the knee.

PMID- 15576718
TI  - Dealing with editorial misconduct.

PMID- 15576720
TI  - Charity warns of "daunting challenges" for Iraq health system.

PMID- 15576721
TI  - Drug misuse in Canada has increased in the past decade.

PMID- 15576722
TI  - Drug related deaths in Europe are falling.

PMID- 15576724
TI  - US healthcare industry sees NHS as "unopened oyster," BMA conference told.

PMID- 15576725
TI  - Ashcroft asks Supreme Court to block Oregon's assisted suicide law.

PMID- 15576727
TI  - Nairobi summit opens with call for action for landmine survivors.

PMID- 15576728
TI  - US threatens Australia over plan to block extensions to drug patents.

PMID- 15576731
TI  - Mother accused of killing son in "fabricated illness" case.

PMID- 15576733
TI  - France passes "right to die" law.

PMID- 15576734
TI  - Regular drinking might explain the French paradox.

PMID- 15576736
TI  - Tobacco chief could be held personally liable for damage to smokers.

PMID- 15576737
TI  - Zimbabwe set to outlaw human rights organisations.

PMID- 15576738
TI  - New 20 year patents threaten to end AIDS drugs for developing countries.

PMID- 15576739
TI  - Red Cross alleged to have complained to US over torture.

PMID- 15576740
TI  - UK patients seek compensation after taking rofecoxib.

PMID- 15576741
TI  - Crisis deepens at the US Food and Drug Administration.

PMID- 15576742
TI  - Sibutramine may be associated with memory impairment.

PMID- 15576743
TI  - Improved access and targeting of musculoskeletal services in northwest Wales:
      targeted early access to musculoskeletal services (TEAMS) programme.
AB  - PROBLEM: The hospital based musculoskeletal service in northwest Wales was unable
      to cope with the demand for referrals from general practitioners. Waiting times
      were long, duplicate referrals to other departments were common, and general
      practitioners were reluctant to refer patients with common problems because of
      the perceived lack of service. Many referrals were made to the inappropriate
      specialty, especially orthopaedics. At least part of this problem was due to a
      lack of coordination between the four hospital departments providing
      musculoskeletal services and the emphasis on district general hospital based
      rather than community provision. DESIGN: Review over 18 months of impact of the
      targeted early access to musculoskeletal services (TEAMS) programme on
      accessibility to musculoskeletal services. SETTING: Northwest Wales. KEY MEASURES
      FOR IMPROVEMENT: Number of patients referred and seen with musculoskeletal
      problems, waiting times, number of duplicate referrals, and surgery conversion
      rates in orthopaedic clinics. STRATEGIES FOR CHANGE: Establishing with central
      clinical triage a common pathway for all musculoskeletal referrals so that
      patients attend the appropriate department. A back pain pathway led by extended
      scope physiotherapists was developed, and general practitioners with special
      interests and extended scope physiotherapists were trained to provide services
      for patients with uncomplicated musculoskeletal problems in the community.
      EFFECTS OF CHANGE: Over 18 months the number of referrals more than doubled.
      Despite this, waiting times for musculoskeletal services fell; this was
      noticeable for rheumatology and pain management. Duplicate referrals were
      abolished. Surgery conversion rates did not, however, change. Questionnaires from
      the clinics showed a high level of patient satisfaction. LESSONS LEARNT:
      Integration of hospital services that traditionally have worked in isolation can
      result in greatly improved access to musculoskeletal services. Community based
      multidisciplinary clinics run by specially trained general practitioners with
      special interests and extended scope physiotherapists are an effective way of
      managing patients with uncomplicated musculoskeletal problems and have been well
      received by patients and general practitioners. The huge unmet burden of need was
      reflected by the great increase in musculoskeletal referrals. Other approaches
      are needed to meet this, including better education of general practitioners and
      methods for identifying and modifying psychosocial risk factors for chronic pain
      at an early stage.

PMID- 15576744
TI  - Tibialis posterior dysfunction: a common and treatable cause of adult acquired
      flatfoot.

PMID- 15576745
TI  - Clomipramine induced neuroleptic malignant syndrome and pyrexia of unknown
      origin.

PMID- 15576746
TI  - Supporting parents in the neonatal unit.

PMID- 15576747
TI  - Democratisation of scientific advice.

PMID- 15576748
TI  - Lessons from the withdrawal of rofecoxib: France has policy for overall
      assessment of public health impact of new drugs.

PMID- 15576749
TI  - Lessons from the withdrawal of rofecoxib: Observational studies should not be
      forgotten.

PMID- 15576751
TI  - Reforming the consultant contract again? Acute trusts should prioritise care of
      urgently ill patients.

PMID- 15576752
TI  - Reforming the consultant contract again? Surgeons' fees for items of service
      would not work.

PMID- 15576753
TI  - Reforming the consultant contract again? Fees for service have been in effect for
      some time.

PMID- 15576754
TI  - Reforming the consultant contract again? Applied in partnership, the contract
      works for both consultants and patients.

PMID- 15576755
TI  - Surgery for carotid artery stenosis: cut-off point is problematic in selecting
      patients for carotid surgery.

PMID- 15576756
TI  - Surgery for carotid artery stenosis: patients with critical stenoses should be
      admitted to stroke prevention units.

PMID- 15576757
TI  - Transparency and trust: Clear definition of ghost writing would be helpful.

PMID- 15576758
TI  - Transparency and trust: in defence of medical writers.

PMID- 15576759
TI  - Transparency and trust: figure for ghost written articles was misquoted.

PMID- 15576760
TI  - Health conventions in smoke free places have positive economic impact.

PMID- 15576761
TI  - Doctors should help patients with their sex lives.

PMID- 15576762
TI  - Every prescription is a clinical trial.

PMID- 15576763
TI  - Signal transduction, quorum-sensing, and extracellular protease activity in
      Enterococcus faecalis biofilm formation.

PMID- 15576764
TI  - Pyruvate oxidase is a determinant of Avery's rough morphology.
AB  - In pioneering studies, Avery et al. identified DNA as the hereditary material (A.
      T. Avery, C. M. MacLeod, and M. McCarty, J. Exp. Med. 79:137-158, 1944). They
      demonstrated, by means of variation in colony morphology, that this substance
      could transform their rough type 2 Streptococcus pneumoniae strain R36A into a
      smooth type 3 strain. It has become accepted as fact, from modern textbook
      accounts of these experiments, that smooth pneumococci make capsule, while rough
      strains do not. We found that rough-to-smooth morphology conversion did not occur
      in rough strains R36A and R6 when the ability to synthesize native type 2 capsule
      was restored. The continued rough morphology of these encapsulated strains was
      attributed to a second, since-forgotten, morphology-affecting mutation that was
      sustained by R36A during strain development. We used a new genome-PCR-based
      approach to identify spxB, the gene encoding pyruvate oxidase, as the mutated
      locus in R36A and R6 that, with unencapsulation, gives rise to rough colony
      morphology, as we know it. The variant spxB allele of R36A and R6 is associated
      with increased cellular pyruvate oxidase activity relative to the ancestral
      strain D39. Increased pyruvate oxidase activity alters colony shape by mediating
      cell death. R36A requires a wild-type spxB allele for the expression of smooth
      type 2 morphology but not for the expression of smooth type 3 morphology, the
      phenotype monitored by Avery et al. Thus, the mutated spxB allele did not impact
      their use of smooth morphology to identify the transforming principle.

PMID- 15576765
TI  - Specialized persister cells and the mechanism of multidrug tolerance in
      Escherichia coli.
AB  - Bacterial populations produce persisters, cells that neither grow nor die in the
      presence of bactericidal agents, and thus exhibit multidrug tolerance (MDT). The
      mechanisms of MDT and the nature of persisters have remained elusive. Our
      previous research has shown that persisters are largely responsible for the
      recalcitrance of biofilm infections. A general method for isolating persisters
      was developed, based on lysis of regular cells by ampicillin. A gene expression
      profile of persisters contained toxin-antitoxin (TA) modules and other genes that
      can block important cellular functions such as translation. Bactericidal
      antibiotics kill cells by corrupting the target function (for example,
      aminoglycosides interrupt translation, producing toxic peptides). We reasoned
      that inhibition of translation will lead to a shutdown of cellular functions,
      preventing antibiotics from corrupting their targets, giving rise to MDT
      persister cells. Overproduction of the RelE toxin, an inhibitor of translation,
      caused a sharp increase in persisters. Functional expression of a putative HipA
      toxin also increased persisters, while deletion of the hipBA module caused a
      sharp decrease in persisters in both stationary and biofilm populations. HipA is
      thus the first validated persister-MDT gene. We suggest that random fluctuation
      in the levels of MDT proteins leads to the formation of rare persister cells. The
      function of these specialized dormant cells is to ensure the survival of the
      population in the presence of lethal factors.

PMID- 15576766
TI  - Evolutionary genetics of the capsular locus of serogroup 6 pneumococci.
AB  - The evolution of the capsular biosynthetic (cps) locus of serogroup 6
      Streptococcus pneumoniae was investigated by analyzing sequence variation within
      three serotype-specific cps genes from 102 serotype 6A and 6B isolates. Sequence
      variation within these cps genes was related to the genetic relatedness of the
      isolates, determined by multilocus sequence typing, and to the inferred patterns
      of recent evolutionary descent, explored using the eBURST algorithm. The serotype
      specific cps genes had a low percent G+C, and there was a low level of sequence
      diversity in this region among serotype 6A and 6B isolates. There was also little
      sequence divergence between these serotypes, suggesting a single introduction of
      an ancestral cps sequence, followed by slight divergence to create serotypes 6A
      and 6B. A minority of serotype 6B isolates had cps sequences (class 2 sequences)
      that were approximately 5% divergent from those of other serotype 6B isolates
      (class 1 sequences) and which may have arisen by a second, more recent
      introduction from a related but distinct source. Expression of a serotype 6A or
      6B capsule correlated perfectly with a single nonsynonymous polymorphism within
      wciP, the rhamnosyl transferase gene. In addition to ample evidence of the
      horizontal transfer of the serotype 6A and 6B cps locus into unrelated lineages,
      there was evidence for relatively frequent changes from serotype 6A to 6B, and
      vice versa, among very closely related isolates and examples of recent
      recombinational events between class 1 and 2 cps serogroup 6 sequences.

PMID- 15576767
TI  - Role of a nosX homolog in Streptococcus gordonii in aerobic growth and biofilm
      formation.
AB  - Oral streptococci such as Streptococcus gordonii are facultative anaerobes that
      initiate biofilm formation on tooth surfaces. An isolated S. gordonii::Tn917-lac
      biofilm-defective mutant contained a transposon insertion in an open reading
      frame (ORF) encoding a homolog of NosX of Ralstonia eutropha, a putative
      maturation factor of nitrous oxide reductase. Located downstream are two genes,
      qor1 and qor2, predicted to encode two putative NADPH quinone oxidoreductases.
      These three genes are cotranscribed, forming a putative oxidative stress response
      (osr) operon in S. gordonii. Inactivation of nosX, qor1, or qor2 resulted in
      biofilm-defective phenotypes. Expression of nosX, measured by the beta
      galactosidase activity of the nosX::Tn917-lac mutant, was growth-phase dependent
      and enhanced when grown under aerobic conditions or in the presence of paraquat.
      Real-time reverse transcription-PCR revealed that nosX-specific mRNA levels were
      increased approximately 8.4 and 3.5 fold in biofilm-derived cells grown on
      plastic and glass, respectively, when compared to planktonic cells. Expression of
      nosX increased 19.9 fold in cells grown under aerated aerobic conditions and 4.7
      fold in cells grown under static aerobic conditions. Two ORFs immediately
      adjacent to the osr operon encode a putative NADH oxidase (Nox) and a putative
      thiol-specific antioxidant enzyme (AhpC, for alkyl hydroperoxide peroxidase C).
      Expression of nox and ahpC was also significantly increased in cells grown under
      aerated and static aerobic conditions when compared to anaerobic conditions. In
      addition, nox expression was increased in biofilm cells compared to planktonic
      cells. These genes may be part of an island that deals with oxidoreductive
      response, some of which may be important in S. gordonii biofilm formation.

PMID- 15576768
TI  - Role and regulation of sigma S in general resistance conferred by low-shear
      simulated microgravity in Escherichia coli.
AB  - Life on Earth evolved in the presence of gravity, and thus it is of interest from
      the perspective of space exploration to determine if diminished gravity affects
      biological processes. Cultivation of Escherichia coli under low-shear simulated
      microgravity (SMG) conditions resulted in enhanced stress resistance in both
      exponential- and stationary-phase cells, making the latter superresistant. Given
      that microgravity of space and SMG also compromise human immune response, this
      phenomenon constitutes a potential threat to astronauts. As low-shear
      environments are encountered by pathogens on Earth as well, SMG-conferred
      resistance is also relevant to controlling infectious disease on this planet. The
      SMG effect resembles the general stress response on Earth, which makes bacteria
      resistant to multiple stresses; this response is sigma s dependent, irrespective
      of the growth phase. However, SMG-induced increased resistance was dependent on
      sigma s only in stationary phase, being independent of this sigma factor in
      exponential phase. sigma s concentration was some 30% lower in exponential-phase
      SMG cells than in normal gravity cells but was twofold higher in stationary-phase
      SMG cells. While SMG affected sigma s synthesis at all levels of control, the
      main reasons for the differential effect of this gravity condition on sigma s
      levels were that it rendered the sigma protein less stable in exponential phase
      and increased rpoS mRNA translational efficiency. Since sigma s regulatory
      processes are influenced by mRNA and protein-folding patterns, the data suggest
      that SMG may affect these configurations.

PMID- 15576769
TI  - Genes involved in the synthesis and degradation of matrix polysaccharide in
      Actinobacillus actinomycetemcomitans and Actinobacillus pleuropneumoniae
      biofilms.
AB  - Biofilms are composed of bacterial cells embedded in an extracellular
      polysaccharide matrix. A major component of the Escherichia coli biofilm matrix
      is PGA, a linear polymer of N-acetyl-D-glucosamine residues in beta(1,6) linkage.
      PGA mediates intercellular adhesion and attachment of cells to abiotic surfaces.
      In this report, we present genetic and biochemical evidence that PGA is also a
      major matrix component of biofilms produced by the human periodontopathogen
      Actinobacillus actinomycetemcomitans and the porcine respiratory pathogen
      Actinobacillus pleuropneumoniae. We also show that PGA is a substrate for
      dispersin B, a biofilm-releasing glycosyl hydrolase produced by A.
      actinomycetemcomitans, and that an orthologous dispersin B enzyme is produced by
      A. pleuropneumoniae. We further show that A. actinomycetemcomitans PGA cross
      reacts with antiserum raised against polysaccharide intercellular adhesin, a
      staphylococcal biofilm matrix polysaccharide that is genetically and structurally
      related to PGA. Our findings confirm that PGA functions as a biofilm matrix
      polysaccharide in phylogenetically diverse bacterial species and suggest that PGA
      may play a role in intercellular adhesion and cellular detachment and dispersal
      in A. actinomycetemcomitans and A. pleuropneumoniae biofilms.

PMID- 15576770
TI  - HMW1 is required for stability and localization of HMW2 to the attachment
      organelle of Mycoplasma pneumoniae.
AB  - The cytoskeletal proteins HMW1 and HMW2 are components of the terminal organelle
      of the cell wall-less bacterium Mycoplasma pneumoniae. HMW1 is required for a
      tapered, filamentous morphology but exhibits accelerated turnover in the absence
      of HMW2. Here, we report that a reciprocal dependency exists between HMW1 and
      HMW2, with HMW2 subject to accelerated turnover with the loss of HMW1.
      Furthermore, the instability of HMW2 correlated with its failure to localize to
      the attachment organelle. The C-terminal domain of HMW1 is essential for both
      function and its accelerated turnover in the absence of HMW2. We constructed HMW1
      deletion derivatives lacking portions of this domain and examined each for
      stability and function. The C-terminal 41 residues were particularly important
      for proper localization and function in cell morphology and P1 localization, but
      the entire C-terminal domain was required to stabilize HMW2. The significance of
      these findings in the context of attachment organelle assembly is considered.

PMID- 15576771
TI  - Characterization of LytA-like N-acetylmuramoyl-L-alanine amidases from two new
      Streptococcus mitis bacteriophages provides insights into the properties of the
      major pneumococcal autolysin.
AB  - Two new temperate bacteriophages exhibiting a Myoviridae (phiB6) and a
      Siphoviridae (phiHER) morphology have been isolated from Streptococcus mitis
      strains B6 and HER 1055, respectively, and partially characterized. The lytic
      phage genes were overexpressed in Escherichia coli, and their encoded proteins
      were purified. The lytAHER and lytAB6 genes are very similar (87% identity) and
      appeared to belong to the group of the so-called typical LytA amidases (atypical
      LytA displays a characteristic two-amino-acid deletion signature). although they
      exhibited several differential biochemical properties with respect to the
      pneumococcal LytA, e.g., they were inhibited in vitro by sodium deoxycholate and
      showed a more acidic pH for optimal activity. However, and in sharp contrast with
      the pneumococcal LytA, a short dialysis of LytAHER or LytAB6 resulted in
      reversible deconversion to the low-activity state (E-form) of the fully active
      phage amidases (C-form). Comparison of the amino acid sequences of LytAHER and
      LytAB6 with that of the pneumococcal amidase suggested that Val317 might be
      responsible for at least some of the peculiar properties of S. mitis phage
      enzymes. Site-directed mutagenesis that changed Val317 in the pneumococcal LytA
      amidase to a Thr residue (characteristic of LytAB6 and LytAHER) produced a fully
      active pneumococcal enzyme that differs from the parental one only in that the
      mutant amidase can reversibly recover the low-activity E-form upon dialysis. This
      is the first report showing that a single amino acid residue is involved in the
      conversion process of the major S. pneumoniae autolysin. Our results also showed
      that some lysogenic S. mitis strains possess a lytA-like gene, something that was
      previously thought to be exclusive to Streptococcus pneumoniae. Moreover, the
      newly discovered phage lysins constitute a missing link between the typical and
      atypical pneumococcal amidases known previously.

PMID- 15576772
TI  - Comparative sequence analysis of IS50/Tn5 transposase.
AB  - Comparative sequence analysis of IS50 transposase-related protein sequences in
      conjunction with known structural, biochemical, and genetic data was used to
      determine domains and residues that play key roles in IS50 transposase function.
      BLAST and ClustalW analyses have been used to find and analyze six complete
      protein sequences that are related to the IS50 transposase. The protein sequence
      identity of these six homologs ranged from 25 to 55% in comparison to the IS50
      transposase. Homologous motifs were found associated with each of the three
      catalytic residues. Residues that play roles in transposase-DNA binding, protein
      autoregulation, and DNA hairpin formation were also found to be conserved in
      addition to other residues of unknown function. On the other hand, some
      homologous sequences did not appear to be competent to encode the inhibitor
      regulatory protein. The results were also used to compare the IS50 transposase
      with the more distantly related transposase encoded by IS10.

PMID- 15576773
TI  - Identification of the Escherichia coli K-12 ybhE gene as pgl, encoding 6
      phosphogluconolactonase.
AB  - We report identification of the Escherichia coli ybhE gene as the pgl gene that
      encodes 6-phosphogluconolactonase. A tentative identification was first made
      based on the known approximate location of the pgl gene and the similarity of the
      presumptive ybhE-encoded protein sequence to a known Pgl enzyme. To test this
      notion, the ybhE gene was deleted and replaced with a drug marker. Like
      previously characterized pgl mutants, the ybhE deletion mutant had a Blu-
      phenotype (dark-blue staining with iodine due to accumulation of starch after
      growth on minimal maltose) and demonstrated impaired growth on minimal glucose
      medium when combined with a pgi mutation. Biochemical assay of crude extracts for
      6-phosphogluconolactonase enzymatic activity showed that ybhE encodes this
      activity. The ybhE gene was transferred from the E. coli chromosome to an
      expression vector. This ybhE clone complemented both the precise deletion of the
      ybhE gene and a larger deletion, pglDelta8, for the Blu- phenotype and for
      phosphogluconolactonase activity, confirming that ybhE is the pgl gene. A newly
      observed phenotype of pgl strains is a lowered frequency of appearance of Bgl+
      mutants that can utilize the beta-glucoside salicin. This is likely due to poor
      growth of Bgl+ pgl strains on salicin due to the accumulation of 6
      phosphogluconolactone.

PMID- 15576774
TI  - Dynamics and control of biofilms of the oligotrophic bacterium Caulobacter
      crescentus.
AB  - Caulobacter crescentus is an oligotrophic alpha-proteobacterium with a complex
      cell cycle involving sessile-stalked and piliated, flagellated swarmer cells.
      Because the natural lifestyle of C. crescentus intrinsically involves a surface
      associated, sessile state, we investigated the dynamics and control of C.
      crescentus biofilms developing on glass surfaces in a hydrodynamic system. In
      contrast to biofilms of the well-studied Pseudomonas aeruginosa, Escherichia
      coli, and Vibrio cholerae, C. crescentus CB15 cells form biphasic biofilms,
      consisting predominantly of a cell monolayer biofilm and a biofilm containing
      densely packed, mushroom-shaped structures. Based on comparisons between the C.
      crescentus strain CB15 wild type and its holdfast (hfsA; DeltaCC0095), pili
      (DeltapilA-cpaF::Omegaaac3), motility (motA), flagellum (flgH) mutants, and a
      double mutant lacking holdfast and flagellum (hfsA; flgH), a model for biofilm
      formation in C. crescentus is proposed. For both biofilm forms, the holdfast
      structure at the tip of a stalked cell is crucial for mediating the initial
      attachment. Swimming motility by means of the single polar flagellum enhances
      initial attachment and enables progeny swarmer cells to escape from the monolayer
      biofilm. The flagellum structure also contributes to maintaining the mushroom
      structure. Type IV pili enhance but are not absolutely required for the initial
      adhesion phase. However, pili are essential for forming and maintaining the well
      defined three-dimensional mushroom-shaped biofilm. The involvement of pili in
      mushroom architecture is a novel function for type IV pili in C. crescentus.
      These unique biofilm features demonstrate a spatial diversification of the C.
      crescentus population into a sessile, "stem cell"-like subpopulation (monolayer
      biofilm), which generates progeny cells capable of exploring the aqueous,
      oligotrophic environment by swimming motility and a subpopulation accumulating in
      large mushroom structures.

PMID- 15576775
TI  - Genetic evidence that catabolites of the Entner-Doudoroff pathway signal C source
      repression of the sigma54 Pu promoter of Pseudomonas putida.
AB  - Glucose and other C sources exert an atypical form of catabolic repression on the
      sigma54-dependent promoter Pu, which drives transcription of an operon for m
      xylene degradation encoded by the TOL plasmid pWW0 in Pseudomonas putida. We have
      used a genetic approach to identify the catabolite(s) shared by all known
      repressive C sources that appears to act as the intracellular signal that
      triggers downregulation of Pu. To this end, we reconstructed from genomic data
      the pathways for metabolism of repressor (glucose, gluconate) and nonrepressor
      (fructose) C sources. Since P. putida lacks fructose-6-phosphate kinase, glucose
      and gluconate appear to be metabolized exclusively by the Entner-Doudoroff (ED)
      pathway, while fructose can be channeled through the Embden-Meyerhof (EM) route.
      An insertion in the gene fda (encoding fructose-1,6-bisphosphatase) that forces
      fructose metabolism to be routed exclusively to the ED pathway makes this sugar
      inhibitory for Pu. On the contrary, a crc mutation known to stimulate expression
      of the ED enzymes causes the promoter to be less sensitive to glucose.
      Interrupting the ED pathway by knocking out eda (encoding 2-dehydro-3
      deoxyphosphogluconate aldolase) exacerbates the inhibitory effect of glucose in
      Pu. These observations pinpoint the key catabolites of the ED route, 6
      phosphogluconate and/or 2-dehydro-3-deoxyphosphogluconate, as the intermediates
      that signal Pu repression. This notion is strengthened by the observation that 2
      ketogluconate, which enters the ED pathway by conversion into these compounds, is
      a strong repressor of the Pu promoter.

PMID- 15576776
TI  - Comparative genomics of the T4-Like Escherichia coli phage JS98: implications for
      the evolution of T4 phages.
AB  - About 130 kb of sequence information was obtained from the coliphage JS98
      isolated from the stool of a pediatric diarrhea patient in Bangladesh. The DNA
      shared up to 81% base pair identity with phage T4. The most conserved regions
      between JS98 and T4 were the structural genes, but their degree of conservation
      was not uniform. The head genes showed the highest sequence conservation,
      followed by the tail, baseplate, and tail fiber genes. Many tail fiber genes
      shared only protein sequence identity. Except for the insertion of endonuclease
      genes in T4 and gene 24 duplication in JS98, the structural gene maps of the two
      phages were colinear. The receptor-recognizing tail fiber proteins gp37 and gp38
      were only distantly related to T4, but shared up to 83% amino acid identity to
      other T6-like phages, suggesting lateral gene transfer. A greater degree of
      variability was seen between JS98 and T4 over DNA replication and DNA transaction
      genes. While most of these genes came in the same order and shared up to 76%
      protein sequence identity, a few rearrangements, insertions, and replacements of
      genes were observed. Many putative gene insertions in the DNA replication module
      of T4 were flanked by intron-related endonuclease genes, suggesting mobile DNA
      elements. A hotspot of genome diversification was located downstream of the DNA
      polymerase gene 43 and the DNA binding gene 32. Comparative genomics of 100-kb
      genome sequence revealed that T4-like phages diversify more by the accumulation
      of point mutations and occasional gene duplication events than by modular
      exchanges.

PMID- 15576777
TI  - Isolation of Escherichia coli bacteriophages from the stool of pediatric diarrhea
      patients in Bangladesh.
AB  - A 3-week coliphage survey was conducted in stool samples from 140 Bangladeshi
      children hospitalized with severe diarrhea. On the Escherichia coli indicator
      strain K803, all but one phage isolate had 170-kb genomes and the morphology of
      T4 phage. In spot tests, the individual T4-like phages infected up to 27 out of
      40 diarrhea-associated E. coli, representing 22 O serotypes and various virulence
      factors; only five of them were not infected by any of these new phages. A
      combination of diagnostic PCR based on g32 (DNA binding) and g23 (major capsid
      protein) and Southern hybridization revealed that half were T-even phages sensu
      strictu, while the other half were pseudo-T-even or even more distantly related
      T4-like phages that failed to cross-hybridize with T4 or between each other.
      Nineteen percent of the acute stool samples yielded T4-like phages, and the
      prevalence was lower in convalescent stool samples. T4-like phages were also
      isolated from environmental and sewage water, but with low frequency and low
      titers. On the enteropathogenic E. coli strain O127:K63, 14% of the patients
      yielded phage, all of which were members of the phage family Siphoviridae with 50
      kb genomes, showing the morphology of Jersey- and beta-4 like phages and narrow
      lytic patterns on E. coli O serotypes. Three siphovirus types could be
      differentiated by lack of cross-hybridization. Only a few stool samples were
      positive on both indicator strains. Phages with closely related restriction
      patterns and, in the case of T4-like phages, identical g23 gene sequences were
      isolated from different patients, suggesting epidemiological links between the
      patients.

PMID- 15576778
TI  - MazF-mediated cell death in Escherichia coli: a point of no return.
AB  - mazEF is a stress-induced toxin-antitoxin module, located on the chromosome of
      Escherichia coli, that we have previously described to be responsible for
      programmed cell death in E. coli. mazF specifies a stable toxin, and mazE
      specifies a labile antitoxin. Recently, it was reported that inhibition of
      translation and cell growth by ectopic overexpression of the toxin MazF can be
      reversed by the action of the antitoxin MazE ectopically overexpressed at a later
      time. Based on these results, it was suggested that rather than inducing cell
      death, mazF induces a state of reversible bacteriostasis (K. Pederson, S. K.
      Christensen, and K. Gerdes, Mol. Microbiol. 45:501-510, 2002). Using a similar
      ectopic overexpression system, we show here that overexpression of MazE could
      reverse MazF lethality only over a short window of time. The size of that window
      depended on the nature of the medium in which MazF was overexpressed. Thus, we
      found "a point of no return," which occurred sooner in minimal M9 medium than it
      did in the rich Luria-Bertani medium. We also describe a state in which the
      effect of MazF on translation could be separated from its effect on cell death:
      MazE overproduction could completely reverse the inhibitory effect of MazF on
      translation, while not affecting the bacteriocidic effect of MazF at all. Our
      results reported here support our view that the mazEF module mediates cell death
      and is part of a programmed cell death network.

PMID- 15576781
TI  - Negative regulation of DNA repair gene (ung) expression by the CpxR/CpxA two
      component system in Escherichia coli K-12 and induction of mutations by increased
      expression of CpxR.
AB  - In Escherichia coli K-12 overexpressing CpxR, transcription of the ung gene for
      uracil-DNA glycosylase was repressed, ultimately leading to the induction of
      mutation. Gel shift, DNase I footprinting, and in vitro transcription assays all
      indicated negative regulation of ung transcription by phosphorylated CpxR. Based
      on the accumulated results, we conclude that ung gene expression is negatively
      regulated by the two-component system of CpxR/CpxA signal transduction.

PMID- 15576779
TI  - Conserved repeat motifs and glucan binding by glucansucrases of oral streptococci
      and Leuconostoc mesenteroides.
AB  - Glucansucrases of oral streptococci and Leuconostoc mesenteroides have a common
      pattern of structural organization and characteristically contain a domain with a
      series of tandem amino acid repeats in which certain residues are highly
      conserved, particularly aromatic amino acids and glycine. In some
      glucosyltransferases (GTFs) the repeat region has been identified as a glucan
      binding domain (GBD). Such GBDs are also found in several glucan binding proteins
      (GBP) of oral streptococci that do not have glucansucrase activity. Alignment of
      the amino acid sequences of 20 glucansucrases and GBP showed the widespread
      conservation of the 33-residue A repeat first identified in GtfI of Streptococcus
      downei. Site-directed mutagenesis of individual highly conserved residues in
      recombinant GBD of GtfI demonstrated the importance of the first tryptophan and
      the tyrosine-phenylalanine pair in the binding of dextran, as well as the
      essential contribution of a basic residue (arginine or lysine). A microplate
      binding assay was developed to measure the binding affinity of recombinant GBDs.
      GBD of GtfI was shown to be capable of binding glucans with predominantly alpha
      1,3 or alpha-1,6 links, as well as alternating alpha-1,3 and alpha-1,6 links
      (alternan). Western blot experiments using biotinylated dextran or alternan as
      probes demonstrated a difference between the binding of streptococcal GTF and GBP
      and that of Leuconostoc glucansucrases. Experimental data and bioinformatics
      analysis showed that the A repeat motif is distinct from the 20-residue CW motif,
      which also has conserved aromatic amino acids and glycine and which occurs in the
      choline-binding proteins of Streptococcus pneumoniae and other organisms.

PMID- 15576780
TI  - TcpH influences virulence gene expression in Vibrio cholerae by inhibiting
      degradation of the transcription activator TcpP.
AB  - Expression of toxT, the transcription activator of cholera toxin and pilus
      production in Vibrio cholerae, is the consequence of a complex cascade of
      regulatory events that culminates in activation of the toxT promoter by TcpP and
      ToxR, two membrane-localized transcription factors. Both are encoded in operons
      with genes whose products, TcpH and ToxS, which are also membrane localized, are
      hypothesized to control their activity. In this study we analyzed the role of
      TcpH in controlling TcpP function. We show that a mutant of V. cholerae lacking
      TcpH expressed virtually undetectable levels of TcpP, although tcpP mRNA levels
      remain unaffected. A time course experiment showed that levels of TcpP, expressed
      from a plasmid, are dramatically reduced over time without co-overexpression of
      TcpH. By contrast, deletion of toxS did not affect ToxR protein levels. A fusion
      protein in which the TcpP periplasmic domain is replaced with that of ToxR
      remains stable, suggesting that the periplasmic domain of TcpP is the target for
      degradation of the protein. Placement of the periplasmic domain of TcpP on ToxR,
      an otherwise stable protein, results in instability, providing further evidence
      for the hypothesis that the periplasmic domain of TcpP is a target for
      degradation. Consistent with this interpretation is our finding that derivatives
      of TcpP lacking a periplasmic domain are more stable in V. cholerae than are
      derivatives in which the periplasmic domain has been truncated. This work
      identifies at least one role for the periplasmic domain of TcpP, i.e., to act as
      a target for a protein degradation pathway that regulates TcpP levels. It also
      provides a rationale for why the V. cholerae tcpH mutant strain is avirulent. We
      hypothesize that regulator degradation may be an important mechanism for
      regulating virulence gene expression in V. cholerae.

PMID- 15576782
TI  - Endopeptidase penicillin-binding proteins 4 and 7 play auxiliary roles in
      determining uniform morphology of Escherichia coli.
AB  - The low-molecular-weight (LMW) penicillin-binding protein, PBP 5, plays a
      dominant role in determining the uniform cell shape of Escherichia coli. However,
      the physiological functions of six other LMW PBPs are unknown, even though the
      existence and enzymatic activities of four of these were established three
      decades ago. By applying fluorescence-activated cell sorting (FACS) to quantify
      the cellular dimensions of multiple PBP mutants, we found that the endopeptidases
      PBP 4 and PBP 7 also influence cell shape in concert with PBP 5. This is the
      first reported biological function for these two proteins. In addition, the
      combined loss of three DD-carboxypeptidases, PBPs 5 and 6 and DacD, also impaired
      cell shape. In contrast to previous reports based on visual inspection alone,
      FACS analysis revealed aberrant morphology in a mutant lacking only PBP 5, a
      phenotype not shared by any other strain lacking a single LMW PBP. PBP 5 removes
      the terminal D-alanine from pentapeptide side chains of muropeptide subunits, and
      pentapeptides act as donors for cross-linking adjacent side chains. As
      endopeptidases, PBPs 4 and 7 cleave cross-links in the cell wall. Therefore,
      overall cell shape may be determined by the existence or location of a specific
      type of peptide cross-link, with PBP 5 activity influencing how many cross-links
      are made and PBPs 4 and 7 acting as editing enzymes to remove inappropriate cross
      links.

PMID- 15576783
TI  - Bacillus subtilis operon encoding a membrane receptor for bacteriophage SPP1.
AB  - The results reported here have identified yueB as the essential gene involved in
      irreversible binding of bacteriophage SPP1 to Bacillus subtilis. First, a
      deletion in an SPP1-resistant (pha-2) strain, covering most of the yueB gene,
      could be complemented by a xylose-inducible copy of yueB inserted at amyE.
      Second, disruption of yueB by insertion of a pMutin4 derivative resulted in a
      phage resistance phenotype regardless of the presence or absence of IPTG
      (isopropyl-beta-D-thiogalactopyranoside). YueB homologues are widely distributed
      in gram-positive bacteria. The protein Pip, which also serves as a phage receptor
      in Lactococcus lactis, belongs to the same family. yueB encodes a membrane
      protein of approximately 120 kDa, detected in immunoblots together with smaller
      forms that may be processed products arising from cleavage of its long
      extracellular domain. Insertional inactivation of yueB and the surrounding genes
      indicated that yueB is part of an operon which includes at least the upstream
      genes yukE, yukD, yukC, and yukBA. Disruption of each of the genes in the operon
      allowed efficient irreversible adsorption, provided that yueB expression was
      retained. Under these conditions, however, smaller plaques were produced, a
      phenotype which was particularly noticeable in yukE mutant strains.
      Interestingly, such reduction in plaque size was not correlated with a decreased
      adsorption rate. Overall, these results provide the first demonstration of a
      membrane-bound protein acting as a phage receptor in B. subtilis and suggest an
      additional involvement of the yukE operon in a step subsequent to irreversible
      adsorption.

PMID- 15576784
TI  - Isolation and expression of the xynB gene and its product, XynB, a consistent
      component of the Clostridium cellulovorans cellulosome.
AB  - The nucleotide sequence of the Clostridium cellulovorans xynB gene, which encodes
      the XynB xylanase, consists of 1,821 bp and encodes a protein of 607 amino acids
      with a molecular weight of 65,976. XynB contains a typical N-terminal signal
      peptide of 29 amino acid residues, followed by a 147-amino-acid sequence that is
      homologous to the family 4-9 (subfamily 9 in family 4) carbohydrate-binding
      domain. Downstream of this domain is a family 10 catalytic domain of glycosyl
      hydrolase. The C terminus separated from the catalytic domain by a short linker
      sequence contains a dockerin domain responsible for cellulosome assembly. The
      XynB sequence from mass spectrometry and N-terminal amino acid sequence analyses
      agreed with that deduced from the nucleotide sequence. XynB was highly active
      toward xylan, but not active toward carboxymethyl cellulose. The enzyme was
      optimally active at 40 degrees C and pH 5.0. Northern hybridizations revealed
      that xynB is transcribed as a monocistronic 1.9-kb mRNA. RNA ligase-mediated
      rapid amplification of 5' cDNA ends by PCR (RLM-5'RACE PCR) analysis of C.
      cellulovorans RNA identified a single transcriptional start site of xynB located
      47 bp upstream from the first nucleotide of the translation initiation codon.
      Alignment of the xynB promoter region provided evidence for highly conserved
      sequences that exhibited strong similarity to the sigmaA consensus promoter
      sequences of gram-positive bacteria. Expression of xynB mRNA increased from early
      to middle exponential phase and decreased during the early stationary phase when
      the cells were grown on cellobiose. No alternative promoter was observed by RLM
      5'RACE PCR and reverse transcriptase PCR analyses during expression. The analysis
      of the products from xylan hydrolysis by thin-layer chromatography indicated its
      endoxylanase activity. The results suggest that XynB is a consistent and major
      cellulosomal enzyme during growth on cellulose or xylan.

PMID- 15576785
TI  - Involvement of SirABC in iron-siderophore import in Staphylococcus aureus.
AB  - Staphylococcus aureus SirA was previously identified as a lipoprotein, and SirB
      and SirC are thought to encode the transmembrane domains of an ABC transporter.
      Sir proteins show similarity to iron-siderophore transporters in several
      bacteria. Here, we show that the iron-regulated sirABC operon is divergently
      transcribed from the sbn operon that encodes enzymes involved in the synthesis of
      staphylobactin, a recently described siderophore produced by S. aureus. Mutation
      of either sirA or sirB increased the resistance of iron-starved S. aureus to
      streptonigrin and resulted in compromised growth in iron-restricted, but not iron
      rich, media. We also demonstrated that sirA and sirB mutants are compromised in
      the ability to transport iron complexed to staphylobactin but are not compromised
      for uptake of other iron complexes, such as ferric hydroxamates, ferric
      enterobactin, or ferric citrate. SirA- and SirB-deficient S. aureus, however,
      retain the ability to produce staphylobactin. Moreover, we found that
      transcription from the sbn operon was increased, relative to the wild type, in
      both sirA and sirB knockout strains, likely in response to an increased level of
      iron starvation in these cells. These results provide evidence of a role for
      these proteins in iron import in S. aureus and for full fitness of the bacterium
      in iron-restricted environments and demonstrate a function for S. aureus genes
      encoding proteins involved in the transport of an endogenously produced
      siderophore.

PMID- 15576786
TI  - In vivo bypass of chaperone by extended coiled-coil motif in T4 tail fiber.
AB  - The distal-half tail fiber of bacteriophage T4 is made of three gene products:
      trimeric gp36 and gp37 and monomeric gp35. Chaperone P38 is normally required for
      folding gp37 peptides into a P37 trimer; however, a temperature-sensitive
      mutation in T4 (ts3813) that suppresses this requirement at 30 degrees C but not
      at 42 degrees C was found in gene 37 (R. J. Bishop and W. B. Wood, Virology
      72:244-254, 1976). Sequencing of the temperature-sensitive mutant revealed a 21
      bp duplication of wild-type gene 37 inserted into its C-terminal portion (S.
      Hashemolhosseini et al., J. Mol. Biol. 241:524-533, 1994). We noticed that the 21
      amino-acid segment encompassing this duplication in the ts3813 mutant has a
      sequence typical of a coiled coil and hypothesized that its extension would
      relieve the temperature sensitivity of the ts3813 mutation. To test our
      hypothesis, we crossed the T4 ts3813 mutant with a plasmid encoding an engineered
      pentaheptad coiled coil. Each of the six mutants that we examined retained two
      amber mutations in gene 38 and had a different coiled-coil sequence varying from
      three to five heptads. While the sequences varied, all maintained the heptad
      repeating coiled-coil motif and produced plaques at up to 50 degrees C. This
      finding strongly suggests that the coiled-coil motif is a critical factor in the
      folding of gp37. The presence of a terminal coiled-coil-like sequence in the tail
      fiber genes of 17 additional T-even phages implies the conservation of this
      mechanism. The increased melting temperature should be useful for "clamps" to
      initiate the folding of trimeric beta-helices in vitro and as an in vivo screen
      to identify, sequence, and characterize trimeric coiled coils.

PMID- 15576787
TI  - Functional analysis of the cell division protein FtsW of Escherichia coli.
AB  - Site-directed mutagenesis experiments combined with fluorescence microscopy shed
      light on the role of Escherichia coli FtsW, a membrane protein belonging to the
      SEDS family that is involved in peptidoglycan assembly during cell elongation,
      division, and sporulation. This essential cell division protein has 10
      transmembrane segments (TMSs). It is a late recruit to the division site and is
      required for subsequent recruitment of penicillin-binding protein 3 (PBP3)
      catalyzing peptide cross-linking. The results allow identification of several
      domains of the protein with distinct functions. The localization of PBP3 to the
      septum was found to be dependent on the periplasmic loop located between TMSs 9
      and 10. The E240-A249 amphiphilic peptide in the periplasmic loop between TMSs 7
      and 8 appears to be a key element in the functioning of FtsW in the septal
      peptidoglycan assembly machineries. The intracellular loop (containing the R166
      F178 amphiphilic peptide) between TMSs 4 and 5 and Gly 311 in TMS 8 are important
      components of the amino acid sequence-folding information.

PMID- 15576788
TI  - Gene ytkD of Bacillus subtilis encodes an atypical nucleoside triphosphatase
      member of the Nudix hydrolase superfamily.
AB  - Gene ytkD of Bacillus subtilis, a member of the Nudix hydrolase superfamily, has
      been cloned and expressed in Escherichia coli. The purified protein has been
      characterized as a nucleoside triphosphatase active on all of the canonical ribo-
      and deoxyribonucleoside triphosphates. Whereas all other nucleoside
      triphosphatase members of the superfamily release inorganic pyrophosphate and the
      cognate nucleoside monophosphate, YtkD hydrolyses nucleoside triphosphates in a
      stepwise fashion through the diphosphate to the monophosphate, releasing two
      molecules of inorganic orthophosphate. Contrary to a previous report, our
      enzymological and genetic studies indicate that ytkD is not an orthologue of E.
      coli mutT.

PMID- 15576789
TI  - Transcriptomic and proteomic characterization of the Fur modulon in the metal
      reducing bacterium Shewanella oneidensis.
AB  - The availability of the complete genome sequence for Shewanella oneidensis MR-1
      has permitted a comprehensive characterization of the ferric uptake regulator
      (Fur) modulon in this dissimilatory metal-reducing bacterium. We have employed
      targeted gene mutagenesis, DNA microarrays, proteomic analysis using liquid
      chromatography-mass spectrometry, and computational motif discovery tools to
      define the S. oneidensis Fur regulon. Using this integrated approach, we
      identified nine probable operons (containing 24 genes) and 15 individual open
      reading frames (ORFs), either with unknown functions or encoding products
      annotated as transport or binding proteins, that are predicted to be direct
      targets of Fur-mediated repression. This study suggested, for the first time,
      possible roles for four operons and eight ORFs with unknown functions in iron
      metabolism or iron transport-related functions. Proteomic analysis clearly
      identified a number of transporters, binding proteins, and receptors related to
      iron uptake that were up-regulated in response to a fur deletion and verified the
      expression of nine genes originally annotated as pseudogenes. Comparison of the
      transcriptome and proteome data revealed strong correlation for genes shown to be
      undergoing large changes at the transcript level. A number of genes encoding
      components of the electron transport system were also differentially expressed in
      a fur deletion mutant. The gene omcA (SO1779), which encodes a decaheme
      cytochrome c, exhibited significant decreases in both mRNA and protein abundance
      in the fur mutant and possessed a strong candidate Fur-binding site in its
      upstream region, thus suggesting that omcA may be a direct target of Fur
      activation.

PMID- 15576790
TI  - Phage phi29 proteins p1 and p17 are required for efficient binding of
      architectural protein p6 to viral DNA in vivo.
AB  - Bacteriophage phi29 protein p6 is a viral architectural protein, which binds
      along the whole linear phi29 DNA in vivo and is involved in initiation of DNA
      replication and transcription control. Protein p1 is a membrane-associated viral
      protein, proposed to attach the viral genome to the cell membrane. Protein p17 is
      involved in pulling phi29 DNA into the cell during the injection process. We have
      used chromatin immunoprecipitation and real-time PCR to analyze in vivo p6
      binding to DNA in cells infected with phi29 sus1 or sus17 mutants; in both cases
      p6 binding is significantly decreased all along phi29 DNA. phi29 DNA is
      topologically constrained in vivo, and p6 binding is highly increased in the
      presence of novobiocin, a gyrase inhibitor that produces a loss of DNA negative
      superhelicity. Here we show that, in cells infected with phi29 sus1 or sus17
      mutants, the increase of p6 binding by novobiocin is even higher than in cells
      containing p1 and p17, alleviating the p6 binding deficiency. Therefore, proteins
      p1 and p17 could be required to restrain the proper topology of phi29 DNA, which
      would explain the impaired DNA replication observed in cells infected with sus1
      or sus17 mutants.

PMID- 15576791
TI  - Effect of mild acid on gene expression in Staphylococcus aureus.
AB  - During staphylococcal growth in glucose-supplemented medium, the pH of a culture
      starting near neutrality typically decreases by about 2 units due to the
      fermentation of glucose. Many species can comfortably tolerate the resulting
      mildly acidic conditions (pH, approximately 5.5) by mounting a cellular response,
      which serves to defend the intracellular pH and, in principle, to modify gene
      expression for optimal performance in a mildly acidic infection site. In this
      report, we show that changes in staphylococcal gene expression formerly thought
      to represent a glucose effect are largely the result of declining pH. We examine
      the cellular response to mild acid by microarray analysis and define the affected
      gene set as the mild acid stimulon. Many of the genes encoding extracellular
      virulence factors are affected, as are genes involved in regulation of virulence
      factor gene expression, transport of sugars and peptides, intermediary
      metabolism, and pH homeostasis. Key results are verified by gene fusion and
      Northern blot hybridization analyses. The results point to, but do not define,
      possible regulatory pathways by which the organism senses and responds to a pH
      stimulus.

PMID- 15576792
TI  - Terminal oxidases are essential to bypass the requirement for ResD for full Pho
      induction in Bacillus subtilis.
AB  - The Bacillus subtilis Pho signal transduction network, which regulates the
      cellular response to phosphate starvation, integrates the activity of three
      signal transduction systems to regulate the level of the Pho response. This
      signal transduction network includes a positive feedback loop between the
      PhoP/PhoR and ResD/ResE two-component systems. Within this network, ResD is
      responsible for 80% of the Pho response. To date, the role of ResD in the
      generation of the Pho response has not been understood. Expression of two
      terminal oxidases requires ResD function, and expression of at least one terminal
      oxidase is needed for the wild-type Pho response. Previously, our investigators
      have shown that strains bearing mutations in resD are impaired for growth and
      acquire secondary mutations which compensate for the loss of the a-type terminal
      oxidases by allowing production of cytochrome bd. We report here that the
      expression of cytochrome bd in a DeltaresDE background is sufficient to
      compensate for the loss of ResD for full Pho induction. A ctaA mutant strain,
      deficient in the production of heme A, has the same Pho induction phenotype as a
      DeltaresDE strain. This demonstrates that the production of a-type terminal
      oxidases is the basis for the role of ResD in Pho induction. Terminal oxidases
      affect the redox state of the quinone pool. Reduced quinones inhibit PhoR
      autophosphorylation in vitro, consistent with a requirement for terminal oxidases
      for full Pho induction in vivo.

PMID- 15576793
TI  - A genetic locus necessary for rhamnose uptake and catabolism in Rhizobium
      leguminosarum bv. trifolii.
AB  - Rhizobium leguminosarum bv. trifolii mutants unable to catabolize the methyl
      pentose rhamnose are unable to compete effectively for nodule occupancy. In this
      work we show that the locus responsible for the transport and catabolism of
      rhamnose spans 10,959 bp. Mutations in this region were generated by transposon
      mutagenesis, and representative mutants were characterized. The locus contains
      genes coding for an ABC-type transporter, a putative dehydrogenase, a probable
      isomerase, and a sugar kinase necessary for the transport and subsequent
      catabolism of rhamnose. The regulation of these genes, which are inducible by
      rhamnose, is carried out in part by a DeoR-type negative regulator (RhaR) that is
      encoded within the same transcript as the ABC-type transporter but is separated
      from the structural genes encoding the transporter by a terminator-like sequence.
      RNA dot blot analysis demonstrated that this terminator-like sequence is
      correlated with transcript attenuation only under noninducing conditions.
      Transport assays utilizing tritiated rhamnose demonstrated that uptake of
      rhamnose was inducible and dependent upon the presence of the ABC transporter at
      this locus. Phenotypic analyses of representative mutants from this locus provide
      genetic evidence that the catabolism of rhamnose differs from previously
      described methyl-pentose catabolic pathways.

PMID- 15576794
TI  - The RpoH-mediated stress response in Neisseria gonorrhoeae is regulated at the
      level of activity.
AB  - The general stress response in Neisseria gonorrhoeae was investigated.
      Transcriptional analyses of the genes encoding the molecular chaperones DnaK,
      DnaJ, and GrpE suggested that they are transcribed from sigma32 (RpoH)-dependent
      promoters upon exposure to stress. This was confirmed by mutational analysis of
      the sigma32 promoter of dnaK. The gene encoding the gonococcal RpoH sigma factor
      appears to be essential, as we could not isolate viable mutants. Deletion of an
      unusually long rpoH leader sequence resulted in elevated levels of transcription,
      suggesting that this region is involved in negative regulation of RpoH expression
      during normal growth. Transcriptional analyses and protein studies determined
      that regulation of the RpoH-mediated stress response is different from that
      observed in most other species, in which regulation occurs predominantly at the
      transcriptional and translational levels. We suggest that an increase in the
      activity of preformed RpoH is primarily responsible for induction of the stress
      response in N. gonorrhoeae.

PMID- 15576795
TI  - Characterization of soluble enzyme II complexes of the Escherichia coli
      phosphotransferase system.
AB  - Plasmid-encoded His-tagged glucose permease of Escherichia coli, the enzyme
      IIBCGlc (IIGlc), exists in two physical forms, a membrane-integrated oligomeric
      form and a soluble monomeric form, which separate from each other on a gel
      filtration column (peaks 1 and 2, respectively). Western blot analyses using anti
      His tag monoclonal antibodies revealed that although IIGlc from the two fractions
      migrated similarly in sodium dodecyl sulfate gels, the two fractions migrated
      differently on native gels both before and after Triton X-100 treatment. Peak 1
      IIGlc migrated much more slowly than peak 2 IIGlc. Both preparations exhibited
      both phosphoenolpyruvate-dependent sugar phosphorylation activity and sugar
      phosphate-dependent sugar transphosphorylation activity. The kinetics of the
      transphosphorylation reaction catalyzed by the two IIGlc fractions were
      different: peak 1 activity was subject to substrate inhibition, while peak 2
      activity was not. Moreover, the pH optima for the phosphoenolpyruvate-dependent
      activities differed for the two fractions. The results provide direct evidence
      that the two forms of IIGlc differ with respect to their physical states and
      their catalytic activities. These general conclusions appear to be applicable to
      the His-tagged mannose permease of E. coli. Thus, both phosphoenolpyruvate
      dependent phosphotransferase system enzymes exist in soluble and membrane
      integrated forms that exhibit dissimilar physical and kinetic properties.

PMID- 15576796
TI  - Revising the role of the pneumococcal vex-vncRS locus in vancomycin tolerance.
AB  - Vancomycin is used increasingly to treat invasive infections caused by multidrug
      resistant Streptococcus pneumoniae. Although no vancomycin-resistant strains have
      been isolated to date, tolerant strains that fail to die rapidly and that cause
      relapsing disease have been described. The vex123-pep27-vncRS locus, consisting
      of an ABC transporter, a presumed signaling peptide, and a two-component system,
      respectively, has been implicated in vancomycin tolerance. Recent findings,
      however, challenged this model. The data presented here indicate that
      erythromycin in the growth medium induces a vancomycin-tolerant phenotype and
      that loss of function of Pep27 or VncRS does not alter autolysis. However, a role
      for the ABC transporter encoded by the vex123 genes in tolerance was confirmed. A
      vex3 mutant was considerably more tolerant to vancomycin treatment than the wild
      type strain T4, and the strength of the phenotype depended on the orientation of
      the resistance cassette used to construct the mutant. Microarray results
      suggested a number of genes that might be involved in tolerance in the vex3
      mutant. Although the exact function and regulation of the vex123-pep27-vncRS
      locus remains to be determined, several factors influence the autolysis behavior
      of S. pneumoniae, including the bacterial capsule, erythromycin, and the lytA and
      vex3 gene products.

PMID- 15576797
TI  - The etiological agent of Lyme disease, Borrelia burgdorferi, appears to contain
      only a few small RNA molecules.
AB  - Small regulatory RNAs (sRNAs) have recently been shown to be the main controllers
      of several regulatory pathways. The function of sRNAs depends in many cases on
      the RNA-binding protein Hfq, especially for sRNAs with an antisense function. In
      this study, the genome of Borrelia burgdorferi was subjected to different
      searches for sRNAs, including direct homology and comparative genomics searches
      and ortholog- and annotation-based search strategies. Two new sRNAs were found,
      one of which showed complementarity to the rpoS region, which it possibly
      controls by an antisense mechanism. The role of the other sRNA is unknown,
      although observed complementarities against particular mRNA sequences suggest an
      antisense mechanism. We suggest that the low level of sRNAs observed in B.
      burgdorferi is at least partly due to the presumed lack of both functional Hfq
      protein and RNase E activity.

PMID- 15576798
TI  - Large-scale identification of genes required for full virulence of Staphylococcus
      aureus.
AB  - Gene products required for in vivo growth and survival of microbial pathogens
      comprise a unique functional class and may represent new targets for
      antimicrobial chemotherapy, vaccine construction, or diagnostics. Although some
      factors governing Staphylococcus aureus pathogenicity have been identified and
      studied, a comprehensive genomic analysis of virulence functions will be a
      prerequisite for developing a global understanding of interactions between this
      pathogen and its human host. In this study, we describe a genetic screening
      strategy and demonstrate its use in screening a collection of 6,300 S. aureus
      insertion mutants for virulence attenuation in a murine model of systemic
      infection. Ninety-five attenuated mutants were identified, reassembled into new
      pools, and rescreened using the same murine model. This effort identified 24
      highly attenuated mutants, each of which was further characterized for virulence
      attenuation in vivo and for growth phenotypes in vitro. Mutants were recovered in
      numbers up to 1,200-fold less than wild type in the spleens of systemically
      infected animals and up to 4,000-fold less than wild type in localized abscess
      infections. Genetic analysis of the mutants identified insertions in 23 unique
      genes. The largest gene classes represented by these mutants encoded enzymes
      involved in small-molecule biosynthesis and cell surface transmembrane proteins
      involved in small-molecule binding and transport. Additionally, three insertions
      defined two histidine kinase sensor-response regulator gene pairs important for
      S. aureus in vivo survival. Our findings extend the understanding of pathogenic
      mechanisms employed by S. aureus to ensure its successful growth and survival in
      vivo. Many of the gene products we have identified represent attractive new
      targets for antibacterial chemotherapy.

PMID- 15576799
TI  - Regulation of sigmaB by an anti- and an anti-anti-sigma factor in Streptomyces
      coelicolor in response to osmotic stress.
AB  - sigmaB, a homolog of stress-responsive sigmaB of Bacillus subtilis, controls both
      osmoprotection and differentiation in Streptomyces coelicolor A3 (2). Its gene is
      preceded by rsbA and rsbB genes encoding homologs of an anti-sigma factor, RsbW,
      and its antagonist, RsbV, of B. subtilis, respectively. Purified RsbA bound to
      sigmaB and prevented sigmaB-directed transcription from the sigBp1 promoter in
      vitro. An rsbA-null mutant exhibited contrasting behavior to the sigB mutant,
      with elevated sigBp1 transcription, no actinorhodin production, and precocious
      aerial mycelial formation, reflecting enhanced activity of sigmaB in vivo.
      Despite sequence similarity to RsbV, RsbB lacks the conserved phosphorylatable
      serine residue and its gene disruption produced no distinct phenotype. RsbV
      (SCO7325) from a putative six-gene operon (rsbV-rsbR-rsbS-rsbT-rsbU1-rsbU) was
      strongly induced by osmotic stress in a sigmaB-dependent manner. It antagonized
      the inhibitory action of RsbA on sigmaB-directed transcription and was
      phosphorylated by RsbA in vitro. These results support the hypothesis that the
      rapid induction of sigmaB target genes by osmotic stress results from modulation
      of sigmaB activity by the kinase-anti-sigma factor RsbA and its phosphorylatable
      antagonist RsbV, which function by a partner-switching mechanism. Amplified
      induction could result from a rapid increase in the synthesis of both sigmaB and
      its inhibitor antagonist.

PMID- 15576800
TI  - RpoS-regulated genes of Escherichia coli identified by random lacZ fusion
      mutagenesis.
AB  - RpoS is a conserved alternative sigma factor that regulates the expression of
      many stress response genes in Escherichia coli. The RpoS regulon is large but has
      not yet been completely characterized. In this study, we report the
      identification of over 100 RpoS-dependent fusions in a genetic screen based on
      the differential expression of an operon-lacZ fusion bank in rpoS mutant and wild
      type backgrounds. Forty-eight independent gene fusions were identified, including
      several in well-characterized RpoS-regulated genes, such as osmY, katE, and otsA.
      Many of the other fusions mapped to genes of unknown function or to genes that
      were not previously known to be under RpoS control. Based on the homology to
      other known bacterial genes, some of the RpoS-regulated genes of unknown
      functions are likely important in nutrient scavenging.

PMID- 15576801
TI  - Cold adaptation in the Antarctic Archaeon Methanococcoides burtonii involves
      membrane lipid unsaturation.
AB  - Direct analysis of membrane lipids by liquid chromatography-electrospray mass
      spectrometry was used to demonstrate the role of unsaturation in ether lipids in
      the adaptation of Methanococcoides burtonii to low temperature. A proteomics
      approach using two-dimensional liquid chromatography-mass spectrometry was used
      to identify enzymes involved in lipid biosynthesis, and a pathway for lipid
      biosynthesis was reconstructed from the M. burtonii draft genome sequence. The
      major phospholipids were archaeol phosphatidylglycerol, archaeol
      phosphatidylinositol, hydroxyarchaeol phosphatidylglycerol, and hydroxyarchaeol
      phosphatidylinositol. All phospholipid classes contained a series of unsaturated
      analogues, with the degree of unsaturation dependent on phospholipid class. The
      proportion of unsaturated lipids from cells grown at 4 degrees C was
      significantly higher than for cells grown at 23 degrees C. 3-Hydroxy-3
      methylglutaryl coenzyme A synthase, farnesyl diphosphate synthase, and
      geranylgeranyl diphosphate synthase were identified in the expressed proteome,
      and most genes involved in the mevalonate pathway and processes leading to the
      formation of phosphatidylinositol and phosphatidylglycerol were identified in the
      genome sequence. In addition, M. burtonii encodes CDP-inositol and CDP-glycerol
      transferases and a number of homologs of the plant geranylgeranyl reductase. It
      therefore appears that the unsaturation of lipids may be due to incomplete
      reduction of an archaeol precursor rather than to a desaturase mechanism. This
      study shows that cold adaptation in M. burtonii involves specific changes in
      membrane lipid unsaturation. It also demonstrates that global methods of analysis
      for lipids and proteomics linked to a draft genome sequence can be effectively
      combined to infer specific mechanisms of key biological processes.

PMID- 15576802
TI  - Hot spot for a large deletion in the 18- to 19-centisome region confers a
      multiple phenotype in Salmonella enterica serovar Typhimurium strain ATCC 14028.
AB  - Loss of the Salmonella MsbB enzyme, which catalyzes the incorporation of
      myristate destined for lipopolysaccharide in the outer membrane, results in a
      strong phenotype of sensitivity to salt and chelators such as EGTA and greatly
      diminished endotoxic activity. MsbB- salmonellae mutate extragenically to EGTA
      tolerant derivatives at a frequency of 10(-4) per division. One of these
      derivatives arose from inactivation of somA, which suppresses sensitivity to salt
      and EGTA. Here we show that a second mode of MsbB- suppression is a RecA
      dependent deletion between two IS200 insertion elements present in Salmonella
      enterica serovar Typhimurium strain ATCC 14028 but not in two other wild-type
      strains, LT2 and SL1344, which lack one of the IS200 elements. This deletion
      occurs spontaneously in wild-type and MsbB- strain 14028 salmonellae and accounts
      for about one-third of all of the spontaneous suppressors of MsbB- in strain
      14028. It spans the region corresponding to 17.7 to 19.9 centisomes, which
      includes somA, on the sequenced map of Salmonella LT2 (136 ORFs in that strain;
      ATCC 14028 and other strains showed variability in this region). In addition to
      conferring EGTA resistance correlated with somA, the deletion confers a MacConkey
      galactose resistance phenotype on MsbB- Salmonella, indicating that at least one
      additional gene (distinct from somA) within the deletion is responsible for this
      phenotype. In the wild type, the deletion mutant grows with normal exponential
      growth rate in Luria broth but is chlorate resistant and does not grow on citrate
      agar. The deletion strains have lost hydrogen sulfide production, nitrate
      reductase activity, and gas production from glucose fermentation.

PMID- 15576803
TI  - The F-ATPase operon promoter of Streptococcus mutans is transcriptionally
      regulated in response to external pH.
AB  - Streptococcus mutans F-ATPase, the major component of the acid-adaptive response
      of the organism, is transcriptionally upregulated at low pH. Fusions of the F
      ATPase promoter to chloramphenicol acetyltransferase indicated that pH-dependent
      expression is still observed with a short promoter that contains a domain
      conserved between streptococcal ATPase operons.

PMID- 15576804
TI  - Identification of a distinct, cryptic heparosan synthase from Pasteurella
      multocida types A, D, and F.
AB  - The extracellular polysaccharide capsules of Pasteurella multocida types A, D,
      and F are composed of hyaluronan, N-acetylheparosan (heparosan or unsulfated,
      unepimerized heparin), and unsulfated chondroitin, respectively. Previously, a
      type D heparosan synthase, a glycosyltransferase that forms the repeating
      disaccharide heparosan backbone, was identified. Here, a approximately 73%
      identical gene product that is encoded outside of the capsule biosynthesis locus
      was also shown to be a functional heparosan synthase. Unlike PmHS1, the PmHS2
      enzyme was not stimulated greatly by the addition of an exogenous polymer
      acceptor and yielded smaller- molecular-weight-product size distributions.
      Virtually identical hssB genes are found in most type A, D, and F isolates. The
      occurrence of multiple polysaccharide synthases in a single strain invokes the
      potential for capsular variation.

PMID- 15576805
TI  - Interaction between the TolC and AcrA proteins of a multidrug efflux system of
      Escherichia coli.
AB  - This paper provides the biochemical evidence for physical interactions between
      the outer membrane component, TolC, and the membrane fusion protein component,
      AcrA, of the major antibiotic efflux pump of Escherichia coli. Cross-linking
      between TolC and AcrA was independent of the presence of any externally added
      substrate of the efflux pump or of the pump protein, AcrB. The biochemical
      demonstration of a TolC-AcrA interaction is consistent with genetic studies in
      which extragenic suppressors of a mutant TolC strain were found in the acrA gene.

PMID- 15576806
TI  - Influence of L-leucine and L-alanine on Lrp regulation of foo, coding for F1651,
      a Pap homologue.
AB  - The foo operon encodes F165 1 fimbriae that belong to the P-regulatory family and
      are synthesized by septicemic Escherichia coli. Using an Lrp-deficient host and
      the lrp gene cloned under the arabinose pBAD promoter, we demonstrated that foo
      was transcribed proportionally to the amount of Lrp synthesized. L-leucine and L
      alanine decreased drastically the steady-state transcription of foo and modified
      phase variation, independently of the presence of FooI. Specific mutations in the
      C-terminal region of Lrp reduced or abolished the repressive effect of these
      amino acids, indicating that they modulate F165 1 by affecting Lrp.

PMID- 15576809
TI  - Characteristics of dental school feeder institutions.

PMID- 15576807
TI  - Activation of the gab operon in an RpoS-dependent manner by mutations that
      truncate the inner core of lipopolysaccharide in Escherichia coli.
AB  - The gab operon (gabDTPC) in Escherichia coli functions in the conversion of gamma
      aminobutyrate to succinate. One component of gab operon regulation involves the
      RpoS sigma factor, which mediates activation at high cell density. Transposon
      mutagenesis was used to identify new genes that regulate gab operon expression in
      rich media. A Tn5tmp insertion in the hldD (formerly rfaD) gene increased
      gabT::lacZ expression 12-fold. The hldD gene product, an ADP-L-glycerol-D
      mannoheptose-6-epimerase, catalyzes the conversion of ADP-D-glycerol-D
      mannoheptose to ADP-L-glycerol-D-mannoheptose, a precursor for the synthesis of
      inner-core lipopolysaccharide (LPS). Defined mutations in hldE, required for
      heptose synthesis, and waaF, required for the addition of the second heptose to
      the inner core, also resulted in high-level gabT::lacZ expression. The hldD,
      hldE, and waaF mutants exhibited a mucoid colony phenotype due to production of a
      colanic acid capsule. However, in the hldD::cat background, the high-level
      expression of gabT::lacZ was independent of the regulatory components for colanic
      acid synthesis (rcsA, rcsB, and rcsC) and also independent of manC (cpsB), a
      structural gene for colanic acid synthesis. Activation of gabT::lacZ in the
      hldD::cat background was dependent on the RpoS sigma factor. The hldD::cat
      mutation resulted in a sixfold increase in the levels of a translational RpoS
      LacZ fusion and had a marginal effect on a transcriptional fusion. This study
      reveals a stress-induced pathway, mediated by loss of the LPS inner core, that
      increases RpoS translation and gab operon expression in E. coli.

PMID- 15576810
TI  - Do repeated clinical competency ratings stereotype students?
AB  - A stereotype is a generalization that protects itself from critique by limiting
      or distorting new information. The potential for stereotyping exists where
      faculty members repeatedly rate students' clinical competency. Stereotyping is
      difficult to study because of methodological problems. If, for example, a
      student's score remains low over repeated ratings, it may be because the faculty
      member has pegged the student as a poor performer or because the student is in
      fact a consistently low performer. An existing dataset of clinical competency
      ratings for almost 300 students was divided so that ratings given by faculty
      members who had evaluated students previously could be compared to ratings of the
      same students by faculty members who had not previously evaluated these students.
      This study supports the following conclusions: 1) repeating faculty members use
      both current information and carryover information from previous rating periods;
      2) the amount of information carried over increases from quarter to quarter; and
      3) faculty evaluators who use more carryover information are more accurate in
      predicting students' graduation competency level than are faculty members on
      their initial ratings of students. In conclusion, there is no evidence in this
      study that repeated clinical competency ratings promote stereotyping of students
      by faculty members.

PMID- 15576811
TI  - Assessing the reliability of a digital preparation assistant system used in
      dental education.
AB  - Use of a digital preparation assistant system may improve considerably the
      quality of preclinical dental education, provided the system works reliably.
      Thus, the purpose of this pilot study was to quantitatively assess the
      reliability of a new preclinical digital preparation assistant system
      (PREPassist, KaVo, Germany). The system was used to repeatedly scan four
      different unprepared and four different prepared teeth both with and without
      repositioning. Corresponding measurements were made to quantify accuracy,
      repeatability, and reproducibility. This was done by estimating the measurement
      error. Based on this estimation, respective limits of agreement were calculated.
      We used these ranges, along with assessments of the measurement's accuracy, to
      judge whether the results satisfy our expectations for clinically acceptable
      measurements. For preclinical laboratory instruction, the results indicate an
      acceptable accuracy (mean accuracy of 89 microm) of the measurements. This
      assessment applies as well to repeatability, given by the range of the respective
      limits of agreement (range <200 microm). However, in the case of reproducibility,
      the limits revealed discrepancies of practical importance (range >200 microm).
      Reproducibility of tooth repositioning in the available mounting device is
      unacceptable for preclinical laboratory instruction because of the observed range
      >200 microm. Thus, there is a need for the manufacture of new and more reliable
      mounting devices because reproducibility procedures are mostly encountered in
      preclinical instruction in restorative techniques. In contrast to
      reproducibility, accuracy and repeatability are acceptable for practical
      purposes. Balancing advantages and disadvantages, we conclude that, in general,
      the PREPassist system delivers reliable results.

PMID- 15576812
TI  - Reasoning process characteristics in the diagnostic skills of beginner,
      competent, and expert dentists.
AB  - The purpose of this study was to evaluate qualitative differences in the
      diagnostic reasoning process at different developmental stages of expertise. A
      qualitative design was used to study cognitive processes that characterize the
      diagnosis of oral disease at the stages of beginner (five junior students who had
      passed the NBDE I), competent (five GPR first-year residents), and expert
      dentists (five general dentists with ten or more years of experience).
      Individually, each participant was asked to determine the diagnosis of an oral
      condition based on a written clinical case, using the think aloud technique and
      retrospective reports. A subsequent interview was conducted to obtain the
      participants' diagnostic process model and pathophysiology of the case. The
      analysis of the verbal protocols indicated that experts referred to the patient's
      sociomedical context more frequently, demonstrated better organization of ideas,
      could determine key clinical findings, and had an ability to plan for the search
      of pertinent information. Fewer diagnostic hypotheses were formulated by
      participants who used forward reasoning, independent of the stage of development.
      Beginners requested additional diagnostic aids (radiographs, laboratory tests)
      more frequently than the competent/expert dentists. Experts recalled typical
      experiences with patients, while competent/beginner dentists recalled information
      from didactic courses. Experts evidenced cognitive diagnostic schemas that
      integrate pathophysiology of disease, while competent and beginner participants
      had not achieved this integration. We conclude that expert performance is a
      combination of a knowledge base, reasoning skills, and an accumulation of
      experiences with patients that is qualitatively different from that of competent
      and beginner dentists. It is important for dental education to emphasize the
      teaching of cognitive processes and to incorporate a wide variety of clinical
      experiences in addition to the teaching of disciplinary content.

PMID- 15576813
TI  - Creating a web-enhanced interactive preclinic technique manual: case report and
      student response.
AB  - This article describes the development, use, and student response to an online
      manual developed with off-the-shelf software and made available using a web-based
      course management system (Blackboard) that was used to transform a freshman
      restorative preclinical technique course from a lecture-only course into an
      interactive web-enhanced course. The goals of the project were to develop and
      implement a web-enhanced interactive learning experience in a preclinical
      restorative technique course and shift preclinical education from a teacher
      centered experience to a student-driven experience. The project was evaluated
      using an anonymous post-course survey (95 percent response rate) of 123 freshman
      students that assessed enabling (technical support and access to the technology),
      process (the actual experience and usability), and outcome criteria (acquisition
      and successful use of the knowledge gained and skills learned) of the online
      manual. Students responded favorably to sections called "slide galleries" where
      ideal and non-ideal examples of projects could be viewed. Causes, solutions, and
      preventive measures were provided for the errors shown. Sections called "slide
      series" provided cookbook directions allowing for self-paced and student-directed
      learning. Virtually all of the students, 99 percent, found the quality of the
      streaming videos adequate to excellent. Regarding Internet connections and video
      viewing, 65 percent of students successfully viewed the videos from a remote
      site; cable connections were the most reliable, dial-up connections were
      inadequate, and DSL connections were variable. Seventy-three percent of the
      students felt the videos were an effective substitute for in-class
      demonstrations. Students preferred video with sound over video with subtitles and
      preferred short video clips embedded in the text over compilation videos. The
      results showed it is possible to develop and implement web-enhanced and
      interactive dental education in a preclinical restorative technique course that
      successfully delivered information beyond the textual format.

PMID- 15576814
TI  - Experience with virtual reality-based technology in teaching restorative dental
      procedures.
AB  - This article reports on extensive experience with advanced simulation at the
      University of Pennsylvania, School of Dental Medicine (UPSDM). Virtual reality
      based technology (VRBT) or advanced simulation is currently available for the
      instruction of dental students in preclinical restorative procedures. UPSDM was
      one of the first schools in the world to have extensive experience with VRBT
      technology using an advanced simulation unit (DentSim) from DenX, Ltd. UPSDM's
      experience consists of several years of research using control and experimental
      groups, employing students to participate in an investigative project, and using
      the units for remediation and a supplement to the preclinical laboratory.
      Currently, all first-year students (Class of 2007 and Class of 2008) are
      receiving most of their preparative operative training on the VRBT units. UPSDM
      started with one (beta) version unit in 1998, which was later updated and
      expanded first to four units and recently to fifteen units. This communication is
      presenting the studies that were of fundamental importance in making the decision
      to acquire fifteen units in 2003. The areas of main interest to the SDM
      concerning this technology were its use in teaching, refreshing, and remediating
      students in restorative procedures and its effectiveness as a teaching
      methodology in relation to time, efficiency, and faculty. Several studies with
      varying parameters were performed at various time points. The limited statistical
      analysis conducted was not conclusive for all measures, and in some cases the
      data only suggest areas of possible significance. This is due to the low number
      of students who could access the limited number of available units and the change
      of protocols in response to student and faculty input. Overall, the results do
      suggest, however, that students learn faster, arrive at the same level of
      performance, accomplish more practice procedures per hour, and request more
      evaluations per procedure or per hour than in our traditional laboratories.
      Students' attitudes, as measured by surveys, group interviews, and private
      interviews, are mixed. Our overall evaluation of our experience with this
      technology has been positive and led to the purchase of additional units, its
      full incorporation into our curriculum, and curriculum revision to maximize its
      potential. Our conclusion is that this technology offers significant potential in
      the field of dental education and that further use and investigation are both
      desired and justified.

PMID- 15576815
TI  - Dental education and evidence-based educational best practices: bridging the
      great divide.
AB  - Research about educational best practices is negatively perceived by many dental
      faculty. Separation between teaching and learning strategies commonly employed in
      dental education and evidence-based educational techniques is real and caused by
      a variety of factors: the often incomprehensible jargon of educational
      specialists; traditional academic dominance of research, publication, and
      grantsmanship in faculty promotions; institutional undervaluing of teaching and
      the educational process; and departmentalization of dental school governance with
      resultant narrowness of academic vision. Clinician-dentists hired as dental
      school faculty may model teaching activities on decades-old personal experiences,
      ignoring recent educational evidence and the academic culture. Dentistry's twin
      internal weaknesses--factionalism and parochialism--contribute to academic
      resistance to change and unwillingness to share power. Dental accreditation is a
      powerful impetus toward inclusion of best teaching and learning evidence in
      dental education. This article will describe how the gap between traditional
      educational strategies and research-based practices can be reduced by several
      approaches including dental schools' promotion of learning cultures that
      encourage and reward faculty who earn advanced degrees in education, regular
      evaluation of teaching by peers and educational consultants with inclusion of the
      results of these evaluations in promotion and tenure committee deliberations,
      creating tangible reward systems to recognize and encourage teaching excellence,
      and basing faculty development programs on adult learning principles. Leadership
      development should be part of faculty enrichment, as effective administration is
      essential to dental school mission fulfillment. Finally, faculty who investigate
      the effectiveness of educational techniques need to make their research more
      available by publishing it, more understandable by reducing educational jargon,
      and more relevant to the day-to-day teaching issues that dental school faculty
      encounter in classrooms, labs, and clinics.

PMID- 15576816
TI  - A model for increasing senior dental student production using private practice
      principles.
AB  - Previous dental graduates have reported a lack of confidence in their ability to
      implement business practices upon graduation. The purpose of the new model was to
      enable senior students to gain experience using sound business principles in
      their senior year. This model involves setting and meeting production goals,
      teamwork, personnel evaluation, and performance incentives. This article reports
      the findings after implementing this model in the academic year 2003-04. Each
      student averaged 226 more charged visits than in 2002-03. Total dollars produced
      increased $7,526 per student, which represented a 63 percent increase in
      production over the previous year. Total dollars produced by the senior class
      increased from $713,740 to $1,066,139 over the previous year. A survey of the
      students' attitudes toward the model showed an increase in acceptance from the
      beginning of the senior year to the end of the year. The model was successful in
      achieving most of the desired outcomes but failed to increase seniors' chairtime
      utilization.

PMID- 15576817
TI  - HIV attitudes and practices among professors in a Brazilian dental school.
AB  - Although there is considerable published research on Acquired Immunodeficiency
      Syndrome (AIDS), individual biases persist because of lack of information
      regarding HIV virus transmission. As a result, both infected patients and health
      care professionals suffer. The objective of this study was to determine if there
      is prejudice among university professors at the School of Dentistry at
      Aracatuba's Sao Paulo State University (FOA-UNESP) concerning HIV-positive
      patients or HIV-positive health care professionals. Out of the seventy-seven
      professors who responded to the questionnaire, 62.3 percent (forty-eight) stated
      that they advise their students not to refuse to treat a patient with HIV.
      Although 96.2 percent (fifty-two) of the fifty-four professors who treat patients
      have reported that they treat patients who are HIV-positive, only 65.3 percent of
      them were aware of infection control precautions, and only 32.7 percent reported
      that they would treat an HIV-positive patient like any other patient. There is
      also prejudice regarding HIV-positive professionals because only 48.1 percent
      (thirty-seven) of the professors responded that they would be willing to be
      treated by an infected professional. It can be concluded that there is prejudice
      among some of the FOA-UNESP university professors regarding individuals who are
      HIV-positive.

PMID- 15576818
TI  - Comparison of dental students selected as student clinicians by Japanese dental
      schools.
AB  - The aim of this study was to determine if students selected from Japanese dental
      schools for competition at the Japan Dental Association meeting and who
      subsequently won awards were different from students who did not win. Eighty
      abstracts submitted from 1995 to 2001 by dental students for the Japan Student
      Clinician Program (SCP) award were evaluated. Multiple logistic regression
      analysis using backward stepwise selection was completed with the dependent
      variables. The results were as follows: 1) more female students won awards than
      did male students, but the difference was not statistically significant; 2)
      students who had a higher level of dental education won more awards, but the
      difference was not statistically significant; and 3) students presenting clinical
      subjects for the table clinic had a higher probability of being selected as prize
      winners (P<.05) than did those dental students presenting basic science subjects.
      Only the subject field of table clinic had a statistical correlation to prize
      winning possibility, which implies that this program fairly evaluated students
      based on a scoring system used by the judges. No discriminations in gender and
      level of dental education were observed. This study suggests that the methodology
      used here might apply to other award programs to determine if the program is
      fair, equal, and unbiased.

PMID- 15576819
TI  - Partners in death.Alzheimer's protein rouses cell-suicide enzyme.

PMID- 15576820
TI  - Paying the price.Long-lived worms can't compete.

PMID- 15576821
TI  - Mitochondrial injury: a hot spot for parkinsonism and Parkinson's disease?
AB  - The recent identification of genes (parkin, DJ-1, and PINK1) involved in
      recessive autosomal parkinsonism, and the indications that these proteins may
      have protective effects on the mitochondria, has led to the reemergence of the
      notion that mitochondrial dysfunction might play a central role in the etiology
      of sporadic Parkinson's disease (PD). This idea has previously been supported by
      biochemical analyses showing reduced mitochondrial activity in PD patients and in
      animal models of PD generated by the selective inhibition of mitochondria
      activity. However, the involvement of DJ-1 or PINK1 loss of function in classical
      idiopathic PD, characterized by pathological inclusions composed of aggregated
      alpha-synuclein protein, has still not been evaluated. More detailed studies of
      the possible interactions between parkin, DJ-1, PINK1, and alpha-synuclein and
      their effects on mitochondria are needed to more adequately define the biological
      pathways that may convergently or independently lead to parkinsonism.

PMID- 15576822
TI  - Changes in vascular perfusion of the endometrium in association with changes in
      location of the embryonic vesicle in mares.
AB  - The equine embryonic vesicle is mobile on Days 12-14 (Day 0 = ovulation), when it
      is approximately 9-15 mm in diameter. Movement from one uterine horn to another
      occurs, on average, approximately 0.5 times per hour. Mobility ceases (fixation)
      on Days 15-17. Transrectal color Doppler ultrasonography was used to study the
      relationship of embryo mobility (experiment 1) and fixation (experiment 2) to
      endometrial vascular perfusion. In experiment 1, mares were bred and examined
      daily from Day 1 to Day 16 and were assigned, retrospectively, to a group in
      which an embryo was detected (pregnant mares; n = 16) or not detected (n = 8) by
      Day 12. Endometrial vascularity (scored 1-4, for none to maximal, respectively)
      did not differ on Days 1-8 between groups or between the sides with and without
      the corpus luteum. Endometrial vascularity scores were higher (P < 0.05) on Days
      12-16 in both horns of pregnant mares compared to mares with no embryo. In
      pregnant mares, the scores increased (P < 0.05) between Day 10 and Day 12 in the
      horn with the embryo and were higher (P < 0.05) than scores in the opposite horn
      on Days 12-15. In experiment 2, 14 pregnant mares were examined from Day 13 to 6
      days after fixation. Endometrial vascularity scores and number of colored pixels
      per cross-section of endometrium were greater (P < 0.05) in the endometrium
      surrounding the fixed vesicle than in the middle portion of the horn of fixation.
      Results supported the hypothesis that transient changes in endometrial vascular
      perfusion accompany the embryonic vesicle as the vesicle changes location during
      embryo mobility.

PMID- 15576823
TI  - Male fertility in natural populations of red deer is determined by sperm velocity
      and the proportion of normal spermatozoa.
AB  - Male reproductive success is determined by the ability of males to gain sexual
      access to females and by their ability to fertilize ova. Among polygynous
      mammals, males differ markedly in their reproductive success, and a great deal of
      effort has been made to understand how selective forces have shaped traits that
      enhance male competitiveness both before and after copulation (i.e., sperm
      competition). However, the possibility that males also may differ in their
      fertility has been ignored under the assumption that male infertility is rare in
      natural populations because selection against it is likely to be strong. In the
      present study, we examined which semen traits correlate with male fertility in
      natural populations of Iberian red deer (Cervus elaphus hispanicus). We found no
      trade-offs between semen traits. Our analyses revealed strong associations
      between sperm production and sperm swimming velocity, sperm motility and
      proportion of morphologically normal spermatozoa, and sperm viability and
      acrosome integrity. These last two variables had the lowest coefficients of
      variation, suggesting that these traits have stabilized at high values and are
      unlikely to be related to fitness. In a fertility trial, our results show a large
      degree of variation in male fertility, and differences in fertility were
      determined mainly by sperm swimming velocity and by the proportion of
      morphologically normal sperm. We conclude that male fertility varies
      substantially in natural populations of Iberian red deer and that, when sperm
      numbers are equal, it is determined mainly by sperm swimming velocity and sperm
      morphology.

PMID- 15576824
TI  - Polyamine synthesis from proline in the developing porcine placenta.
AB  - Polyamines (putrescine, spermidine, and spermine) are essential for placental
      growth and angiogenesis. However, little is known about polyamine synthesis in
      the porcine placenta during conceptus development. The present study was
      conducted to test the hypothesis that arginine and proline are the major sources
      of ornithine for placental polyamine production in pigs. Placentae, amniotic
      fluid, and allantoic fluid were obtained from gilts on Days 20, 30, 35, 40, 45,
      50, 60, 90, and 110 of the 114-day gestation (n = 6 per day). Placentae as well
      as amniotic and allantoic fluids were analyzed for arginase, proline oxidase,
      ornithine aminotransferase (OAT), ornithine decarboxylase (ODC), proline
      transport, concentrations of amino acids and polyamines, and polyamine synthesis
      using established radiochemical and chromatographic methods. Neither arginase
      activity nor conversion of arginine into polyamines was detected in the porcine
      placenta. In contrast, both proline and ornithine were converted into putrescine,
      spermidine, and spermine in placental tissue throughout pregnancy. The activities
      of proline oxidase, OAT, and ODC as well as proline transport, polyamine
      synthesis from proline, and polyamine concentrations increased markedly between
      Days 20 and 40 of gestation, declined between Days 40 and 90 of gestation, and
      remained at the reduced level through Day 110 of gestation. Proline oxidase and
      OAT, but not arginase, were present in allantoic and amniotic fluids for the
      production of ornithine (the immediate substrate for polyamine synthesis). The
      activities of these two enzymes as well as the concentrations of ornithine and
      total polyamines in fetal fluids were highest at Day 40 but lowest at Days 20,
      90, and 110 of gestation. These results indicate that proline is the major amino
      acid for polyamine synthesis in the porcine placenta and that the activity of
      this synthetic pathway is maximal during early pregnancy, when placental growth
      is most rapid. Our novel findings provide a new base of information for future
      studies to define the role of proline in fetoplacental growth and development.

PMID- 15576825
TI  - Alkylated imino sugars, reversible male infertility-inducing agents, do not
      affect the genetic integrity of male mouse germ cells during short-term treatment
      despite induction of sperm deformities.
AB  - Reversible infertility can be induced in male mice by oral administration of the
      alkylated imino sugars N-butyldeoxynojirimycin (NB-DNJ) and N
      butyldeoxygalactonojirimycin (NB-DGJ). Spermatozoa of these mice have grossly
      misshapen heads and reduced motility. Because NB-DNJ and related compounds may
      hold promise as nonhormonal male contraceptives, a comprehensive examination of
      their effects on male reproduction is necessary. To this end, we further examined
      reproductive properties of the dysmorphic spermatozoa that are produced after
      short-term imino sugar administration at the minimal dose that completely
      abolishes the ability of male C57BL/6 mice to produce offspring by natural
      mating. Here, we report that, in vitro, the abnormal spermatozoa from the NB-DNJ-
      and NB-DGJ-treated mice were unable to fertilize oocytes. In addition, we
      investigated whether the imino sugars damage the genetic integrity of
      spermatozoa. To test this, we microsurgically injected deformed spermatozoa from
      imino sugar-treated males into oocytes. The deformed spermatozoa from the testis
      were able to activate oocytes very efficiently, but those from the cauda
      epididymis often failed to do so. This problem was overcome when the sperm
      injected oocytes were treated with a parthenogenetic agent, Sr(2+). Oocytes
      injected with the misshapen spermatozoa from NB-DNJ- and NB-DGJ-treated mice
      developed (with or without Sr(2+) treatment) into live offspring that grew
      normally and were normally fertile. This indicates that during short-term
      administration, alkylated imino sugars alter sperm morphology and physiology but
      do not diminish the genetic potential of spermatozoa.

PMID- 15576827
TI  - Leukocyte subpopulations in the uteri of leukemia inhibitory factor knockout mice
      during early pregnancy.
AB  - Leukemia inhibitory factor (LIF) is transiently expressed on Day (D) 1 of
      pregnancy by the uterine epithelium and on D4 specifically by the glandular
      epithelium. The Lif knockout female mice are infertile because of uterine defects
      that affect embryo implantation, but pregnancy can be rescued in these mice by
      injections of LIF on D4 of pregnancy. Many of the specific actions of LIF in the
      uterus are unknown, especially with regard to uterine cell biology. Leukocytes,
      such as macrophages, natural killer (NK) cells, and eosinophils, are present in
      the pregnant uterus and are thought to be beneficial, because alterations in
      their proportions can adversely affect pregnancy. Immunocytochemistry and cell
      counting were used to compare the distributions and dynamics of leukocyte
      subpopulations in wild-type and Lif knockout mice. The percentage of macrophages
      was reduced by more than half in the Lif knockout mice on D3 of pregnancy, and
      their distribution was disrupted, suggesting that LIF is a chemokine for these
      cells. The NK cells were detected as early as D3 of pregnancy, but the Lif
      knockout mice had double the percentage of NK cells compared to wild-type mice at
      this time, indicating that LIF restricts the migration of NK cells to the uterus.
      The Lif knockout mice also had significantly higher percentages of eosinophils in
      the outer stroma on D3, and in the midstroma on D4, of pregnancy, suggesting that
      LIF also may restrict eosinophil migration to the uterus. These alterations of
      the uterine leukocyte subpopulations in Lif knockout mice may disrupt pregnancy
      and contribute to failure of implantation.

PMID- 15576826
TI  - Hepatocyte growth factor regulation of uterine epithelial cell transepithelial
      resistance and tumor necrosis factor alpha release in culture.
AB  - Underlying stromal cells are essential for the normal development of epithelial
      cells (ECs) at mucosal surfaces. Recent studies from our laboratory have shown
      that uterine stromal cells regulate EC integrity, measured as transepithelial
      resistance (TER) as well as tumor necrosis factor (TNF) alpha alpha secretion by
      ECs in culture. Using stromal cells in coculture with polarized ECs grown on
      inserts, we found that stromal cells produce soluble mediators that increase TER
      and decrease TNFalpha secretion. The purpose of the present study was to identify
      the mechanisms whereby stromal cells exert their effects on uterine epithelium.
      We report that hepatocyte growth factor (HGF), a known mesenchymal growth factor
      that mediates EC proliferation, increases TER but, at the same time, decreases
      apical TNFalpha release. When ECs and/or stromal cells were incubated with anti
      HGF or anti-HGF receptor (HGFR) antibody before HGF, the effects of HGF were
      blocked. These findings indicate that ECs express the HGFR at their basolateral
      surfaces and that HGFR mediates the effects of HGF on TER and TNFalpha.
      Neutralization of stromal cell secretions with antibodies for HGF and HGFR
      demonstrate that stromal-derived HGF is the mediator of EC TER. In contrast,
      neither anti-HGF antibody nor HGFR antibody had any effect on stromal cell
      induced decreases in TNFalpha secretion. From these results, we conclude that
      stromal cell regulation of EC TER is mediated through the secretion of stromal
      HGF. Furthermore, because neutralization of stromal media failed to affect
      TNFalpha secretion, these findings suggest that other growth factors, in addition
      to HGF, affect EC cytokine production.

PMID- 15576828
TI  - Differential effects of estrogen and raloxifene on messenger RNA and matrix
      metalloproteinase 2 activity in the rat uterus.
AB  - A detailed analysis of the differential effects of estrogen (E) compared to
      raloxifene (Ral), a selective estrogen receptor modulator (SERM), following
      estrogen receptor (ER) binding in gynecological tissues was conducted using gene
      microarrays, Northern blot analysis, and matrix metalloproteinase (MMP) 2
      activity studies. We profiled gene expression in the uterus following acute (1
      day) and prolonged daily (5 wk) treatment of E and Ral in ovariectomized rats.
      Estrogen regulated twice as many genes as Ral, largely those associated with
      catalysis and metabolism, whereas Ral induced genes associated with cell death
      and negative cell regulation. Follow-up studies confirmed that genes associated
      with matrix integrity were differentially regulated by Ral and E at various time
      points in uterine and vaginal tissues. Additional experiments were conducted to
      determine the levels of MMP2 activity in uterus explants from ovariectomized rats
      following 2 wk of treatment with E, Ral, or one of two additional SERMs:
      lasofoxifene, and levormeloxifene. Both E and lasofoxifene stimulated uterine
      MMP2 activity to a level twofold that of Ral, whereas levormeloxifene elevated
      MMP2 activity to a level 12-fold that of Ral. These data show that one of the
      significant differences between E and Ral signaling in the uterus is the
      regulation of genes and proteins associated with matrix integrity. This may be a
      potential key difference between the action of SERMs in the uterus of
      postmenopausal women.

PMID- 15576829
TI  - Cloning and characterization of the 5alpha-reductase type 2 promoter in the rat
      epididymis.
AB  - Steroid 5alpha-reductase converts testosterone to the more potent androgen,
      dihydrotestosterone. The molecular mechanisms responsible for maintaining high
      concentrations of the 5alpha-reductase type 2 mRNA in the caput epididymidis and
      for regulating its region-specific expression are unknown. To gain insight into
      its transcriptional regulation, the cloning and characterization of the 5'
      upstream region of 5alpha-reductase type 2 were undertaken. Sequential deletion
      analysis was done to map the 2243-base pair (bp) cloned 5' upstream region, and
      the constructs were transfected into epididymal PC1 cells and prostatic PC3
      cells. In both cell lines, regulatory elements and the minimal promoter were
      mapped to the 485-bp region upstream of the start codon. Primer extension and 5'
      RACE identified one transcriptional start site at 33-bp upstream of the start
      codon. Using electrophoretic mobility shift assay, a specific band was observed
      in the -68- to -32-bp region in the presence of nuclear extracts. Supershift and
      mutational studies confirmed the binding of SP1 and, to a lesser extent, SP3 to
      the two potential SP1 binding sites and the preference of these proteins to one
      binding site over the other. SP1 and SP3 were both predominantly immunolocalized
      to the principal cells of the epididymis and follow distinct distribution
      patterns in this tissue. These results provide a framework crucial in the further
      investigation of the transcriptional regulation of 5alpha-reductase type 2 in the
      rat epididymis.

PMID- 15576830
TI  - Isolation and enrichment of murine spermatogonial stem cells using rhodamine 123
      mitochondrial dye.
AB  - Stem cells possess enormous therapeutic potential in tissue replacement. To study
      stem cells further, they must be isolated. Techniques are available for
      enrichment and study of hematopoietic stems cells, but thus far, techniques for
      purification of spermatogonial stem cells have not been described. Enrichment
      techniques for hematopoietic stem cells include the use of fluorescence-activated
      cell sorter analysis with Hoechst 33342 and rhodamine 123 (Rho) dyes. Use of
      Hoechst dye to isolate spermatogonial stem cells has been unsuccessful in our
      laboratory, and our results have conflicted with those from other laboratories.
      Taking advantage of the differential staining of the Rho dye, we report a novel
      method to enrich murine spermatogonial stem cells. Testicular cells are harvested
      from cryptorchid ROSA26 male mice. Populations of these cells are then stained
      with the Hoechst and Rho dyes, allowing them to be sorted by flow cytometry into
      a side population (SP) of Hoechst low-intensity cells and populations of low
      (Rho(low)) or high (Rho(hi)) fluorescent intensity. Sterile recipients, W/W(v)
      mice, with an intrinsic germ cell deficiency were transplanted with the Hoechst
      SP cells, Rho(low), Rho(hi), and nonsorted donor cells. No spermatogonial stem
      cell colonies were derived from the Hoechst SP cells. The number of
      spermatogonial stem cell colonies from transplanted Rho(low) cells showed a 17-
      and 20-fold enrichment over those of Rho(hi) and nonsorted cells, respectively.

PMID- 15576831
TI  - Focus on treatment of large hepatocellular carcinoma.

PMID- 15576832
TI  - Differential association of BRCA1 and BRCA2 genes with some breast cancer
      associated genes in early and late onset breast tumors.
AB  - BACKGROUND: Accumulating evidence indicating more aggressive features of breast
      carcinoma (BC) in young women than their older counterparts have raised the
      question of whether these differences are present at the genetic level. METHODS:
      For this purpose, we performed a comparative analysis of the frequency of
      deletions of BRCA1, BRCA2, BRCAX, TP53, ATM, and RB1 and amplification of Cyclin
      D1 and also studied the interrelation and prognostic significance of these
      genetic alterations in 30 early onset (< or =40 years) and 33 late onset (>40
      years) cases of BC. These gene alterations were also studied in 11 other types of
      breast lesions. RESULTS: A differential pattern of alterations
      (deletion/amplification) was observed in the two age groups, with the sequence in
      younger women being BRCA1 (72%), TP53 (71%), ATM (64%), BRCA2 (62%), RB1 (60%),
      Cyclin D1 (43%), and BRCAX (24%) and that in the older group being TP53 (66%),
      RB1 (63%), BRCA1 (56%), ATM (53%), BRCA2 (45%), Cyclin D1 (24%), and BRCAX (23%).
      Similar, differential correlations were also seen with several
      clinicopathological parameters, prognosis, and combinations of alterations among
      these genes in the two age groups. CONCLUSIONS: Differential frequencies and
      interrelationships of genetic alterations and prognoses in these two age groups
      indicate that the molecular pathways for the development of tumors in both age
      groups may not be similar, though the ultimate effect is deregulation of cell
      cycle checkpoints and defects in the DNA repair pathway.

PMID- 15576833
TI  - A critical assessment of adjuvant radiotherapy for inguinal lymph node metastases
      from melanoma.
AB  - BACKGROUND: Although patients with inguinal or pelvic lymph node (LN) metastases
      from melanoma may develop regional recurrence after dissection, the role of
      adjuvant radiotherapy remains controversial. METHODS: The medical records of 40
      patients with inguinal and/or pelvic lymph node metastases from melanoma were
      reviewed retrospectively. Indications for adjuvant radiotherapy included the
      following nodal characteristics: extracapsular extension, LNs > or =3 cm in
      diameter, > or =4 involved LNs, and LN recurrence after prior nodal surgery.
      Thirty-seven of 40 patients underwent formal LN dissection. Three patients had
      only local excision of gross disease for recurrence after prior dissection. All
      patients received radiation to a median dose of 30 Gy at six Gy/fraction
      delivered twice weekly. RESULTS: With a median follow-up time of 22.5 months, the
      3-year actuarial distant metastasis-free and overall survival rates were 35% and
      38%, respectively. The 3-year regional control rate was 74%. Univariate analyses
      of patient, tumor, and treatment characteristics failed to reveal any association
      with distant metastasis-free survival, overall survival, or regional control.
      Regional failures occurred in nine patients; seven of these were isolated dermal
      failures within the field of irradiation. Only two patients (5%) had LN basin
      recurrences; one of these patients also developed dermal recurrence. Fifteen of
      40 patients developed lymphedema; in seven of these, lymphedema was present
      before initiation of radiation therapy. CONCLUSIONS: Radiation may prevent
      recurrence of nodal disease in patients at high risk for regional failure, but in
      field dermal recurrences may sometimes occur (8 of 40, 20%). Treatment-related
      lymphedema and death from metastatic melanoma were common.

PMID- 15576834
TI  - Thyroid cancer: is the incidence still increasing?
AB  - BACKGROUND: The objective of this study was to define the epidemiology of thyroid
      cancer in our regional population and compare results with Surveillance,
      Epidemiology, and End RESULTS (SEER) Program cancer registry trends. METHODS:
      Thyroid cancer cases diagnosed between 1990 and 2000 were identified in the
      Florida Cancer Data System (FCDS). Overall, gender-specific, age-specific, and
      stage-specific incidence rates were calculated. All rates are per 100,000 and age
      adjusted to the 2000 U.S. standard population. Estimated Annual Percent Change
      (EAPC) was calculated with a linear least-squares model. RESULTS: Patients with
      thyroid cancer (n = 8603) were identified in the FCDS registry. Age-adjusted
      incidence rates increased from 4.2 per 100,000 to 7 per 100,000 in 2000. The EAPC
      for this period was 5.5% (P < .001). The SEER incidence rates increased from 7.9
      to 10.2 per 100,000, and the EAPC was 3.7% (P < .05). Analysis of gender-specific
      incidence rates showed increases from 6 and 2.2 per 100,000 in 1990 to 10.1 and
      3.8 per 100,000 in 2000 among females and males, respectively, with EAPCs of 5.9%
      (females) and 4.5% (males) (P < .001). With stratification by age group, the
      highest incidence rates were 9 per 100,000 in the group aged 65 to 84 years and
      8.4 per 100,000 in the group aged 45 to 64 years. CONCLUSIONS: Thyroid cancer
      incidence rates in Florida almost doubled over the 1990-2000 period and are
      concordant with SEER trends. Etiologic studies addressing temporal changes in
      reproductive factors, more intensive diagnostic activities, and changes in
      histological criteria are warranted.

PMID- 15576835
TI  - Sixteen hours of fasting differentially affects hepatic and muscle insulin
      sensitivity in mice.
AB  - Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with
      hepatic insulin resistance. The purpose of the present study was to document the
      effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and
      skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and
      2) changes in mRNA expression of metabolically relevant genes. Sixteen hours of
      fasting did not show an effect on hepatic insulin sensitivity in terms of glucose
      production in the presence of increased hepatic TG content. In muscle, however,
      fasting resulted in increased insulin sensitivity, with increased muscle glucose
      uptake without changes in muscle TG content. In liver, fasting resulted in
      increased mRNA expression of genes promoting gluconeogenesis and TG synthesis but
      in decreased mRNA expression of genes involved in glycogenolysis and fatty acid
      synthesis. In muscle, increased mRNA expression of genes promoting glucose
      uptake, as well as lipogenesis and beta-oxidation, was found. In conclusion, 16 h
      of fasting does not induce hepatic insulin resistance, although it causes liver
      steatosis, whereas muscle insulin sensitivity increases without changes in muscle
      TG content. Therefore, fasting induces differential changes in tissue-specific
      insulin sensitivity, and liver and muscle TG contents are unlikely to be involved
      in these changes.

PMID- 15576836
TI  - Phosphatidylinositol increases HDL-C levels in humans.
AB  - Studies have shown that phosphatidylinositol (PI) can stimulate reverse
      cholesterol transport by enhancing the flux of cholesterol into HDL and by
      promoting the transport of high density lipoprotein-cholesterol (HDL-C) to the
      liver and bile. The goal of this study was to determine the safety and
      therapeutic value of PI after oral administration to normolipidemic human
      subjects. We performed a randomized 2 week study in 16 normolipidemic subjects.
      Subjects received either 2.8 or 5.6 g of PI, with or without food. PI was well
      tolerated by all subjects. PI significantly affected the levels of HDL-C and
      triglyceride in the plasma of subjects receiving PI with food. The lower dose
      showed a 13% increase in HDL-C, whereas the high dose showed an increase of 18%
      over the 2 week period. Both low- and high-dose groups showed significant
      increases in plasma apolipoprotein A-I. The high dose of PI also decreased plasma
      triglycerides by 36% in the fed subjects. These data suggest that after only 2
      weeks, PI may have a comparable therapeutic value to niacin, with negligible side
      effects.

PMID- 15576837
TI  - Expression of the endothelial lipase gene in murine embryos and reproductive
      organs.
AB  - Endothelial lipase (EL) is a recently discovered member of the triglyceride
      lipase family that is involved in plasma HDL metabolism. In this study, we
      investigated the putative role of EL in mouse reproduction by studying EL gene
      expression in mouse embryos and adult reproductive organs. PCR analysis revealed
      that EL mRNA is expressed in mouse embryos on embryonic day 8.5 (E8.5) to E11.5,
      but not later in development. In situ hybridization studies on E10.5 whole
      embryos and embryonic sections showed expression of EL mRNA in multiple tissues,
      although of varying intensity. High expression was found in the neuroepithelium
      of the brain and the neural tube, the mesenchymal cells between organs, the optic
      lens and cup, and the otocyst. In adult mice, EL mRNA expression was high in
      ovaries from pregnant mice but low in ovaries from nonpregnant mice. EL mRNA was
      also highly expressed in placenta and testes. In situ hybridization studies
      demonstrated intense EL mRNA staining of lutein cells in corpora lutei in
      ovaries, of spermatocytes in the late pachytene and diplotene stages in testes,
      and of principal cells in epididymis. These results suggest that EL, in addition
      to its effects on plasma lipoprotein metabolism, plays a role in murine
      reproduction.

PMID- 15576838
TI  - DGAT1 overexpression in muscle by in vivo DNA electroporation increases
      intramyocellular lipid content.
AB  - In adipose tissue, the microsomal enzyme 1,2-acyl CoA:diacylglyceroltransferase-1
      (DGAT1) plays an important role in triglyceride storage. Because DGAT1 is
      expressed in skeletal muscle as well, we aimed to directly test the effect of
      DGAT1 on muscular triglyceride storage by overexpressing DGAT1 using in vivo DNA
      electroporation. A pcDNA3.1-DGAT1 construct in saline was injected in the left
      tibialis anterior muscle of rats, followed by the application of eight
      transcutaneous pulses, using the contralateral leg as sham-electroporated
      control. Electroporation of the DGAT1 construct led to significant overexpression
      of the DGAT1 protein. The functionality of DGAT1 overexpression is underscored by
      the pronounced diet-responsive increase in intramyocellular lipid (IMCL) storage.
      In chow-fed rats, DGAT1-positive myocytes showed significantly higher IMCL
      content compared with the control leg, which was almost devoid of IMCL (1.99 +/-
      1.13% vs. 0.017 +/- 0.014% of total area fraction; P <0.05). High-fat feeding
      increased IMCL levels in both DGAT1-positive and control myocytes, resulting in
      very high IMCL levels in DGAT1-overexpressing myocytes (4.96 +/- 1.47% vs. 0.80
      +/- 0.14%; P <0.05). Our findings indicate that DGAT1 contributes to the storage
      of IMCL and that in vivo DNA electroporation is a promising tool to examine the
      functional consequences of altered gene expression in mature skeletal muscle.

PMID- 15576839
TI  - Impaired response of biliary lipid secretion to a lithogenic diet in
      phosphatidylcholine transfer protein-deficient mice.
AB  - Phosphatidylcholine transfer protein (PC-TP) is a cytosolic lipid transfer
      protein that is highly expressed in liver and catalyzes intermembrane transfer of
      phosphatidylcholines in vitro. To explore a role for PC-TP in the hepatocellular
      trafficking of biliary phosphatidylcholines, we characterized biliary lipid
      secretion using Pctp(-/-) and wild-type littermate control mice with C57BL/6J and
      FVB/NJ genetic backgrounds, which express PC-TP at relatively high and low levels
      in liver, respectively. Eight-week-old male Pctp(-/-) and wild-type mice were fed
      a chow diet or a lithogenic diet, which served to upregulate biliary lipid
      secretion. In chow-fed mice, the absence of PC-TP did not reduce biliary
      phospholipid secretion or alter the phospholipid composition of biles. However,
      the responses in secretion of biliary phospholipids, cholesterol, and bile salts
      to the lithogenic diet were impaired in Pctp(-/-) mice from both genetic
      backgrounds. Alterations in biliary lipid secretion could not be attributed to
      transcriptional regulation of the expression of canalicular membrane lipid
      transporters, but possibly to a defect in their trafficking to the canalicular
      membrane. These findings support a role for PC-TP in the response of biliary
      lipid secretion to a lithogenic diet, but not specifically in the hepatocellular
      transport and secretion of phosphatidylcholines.

PMID- 15576840
TI  - The postmortal accumulation of brain N-arachidonylethanolamine (anandamide) is
      dependent upon fatty acid amide hydrolase activity.
AB  - N-arachidonylethanolamine (AEA) accumulates during brain injury and postmortem.
      Because fatty acid amide hydrolase (FAAH) regulates brain AEA content, the
      purpose of this study was to determine its role in the postmortal accumulation of
      AEA using FAAH null mice. As expected, AEA content in immediately frozen brain
      tissue was significantly greater in FAAH-deficient (FAAH-/-) than in wild-type
      mice. However, AEA content was significantly lower in brains from FAAH-/- mice at
      5 and 24 h postmortem. Similarly, wild-type mice treated in vivo with a FAAH
      inhibitor (URB532) had significantly lower brain AEA content 24 h postmortem
      compared with controls. These data indicate that FAAH contributes significantly
      to the postmortal accumulation of AEA. In contrast, the accumulations of two
      other N-acylethanolamines, N-oleoylethanolamine (OEA) and N-palmitoylethanolamine
      (PEA), were not reduced at 24 h postmortem in either the FAAH-/- mice or mice
      treated with URB532. FAAH-/- mice accumulated significantly less ethanolamine at
      24 h postmortem compared with wild-type mice, suggesting that FAAH activity plays
      a role in the accumulation of ethanolamine postmortem. These data demonstrate
      that FAAH activity differentially affects AEA and OEA/PEA contents postmortem and
      suggest that AEA formation specifically occurs via an ethanolamine-dependent
      route postmortem.

PMID- 15576841
TI  - Downstream effects on human low density lipoprotein of homocysteine exported from
      endothelial cells in an in vitro system.
AB  - A model system is presented using human umbilical vein endothelial cells (HUVECs)
      to investigate the role of homocysteine (Hcy) in atherosclerosis. HUVECs are
      shown to export Hcy at a rate determined by the flux through the methionine/Hcy
      pathway. Additional methionine increases intracellular methionine, decreases
      intracellular folate, and increases Hcy export, whereas additional folate
      inhibits export. An inverse relationship exists between intracellular folate and
      Hcy export. Hcy export may be regulated by intracellular S-adenosyl methionine
      rather than by Hcy. Human LDLs exposed to HUVECs exporting Hcy undergo time
      related lipid oxidation, a process inhibited by the thiol trap
      dithionitrobenzoate. This is likely to be related to the generation of hydroxyl
      radicals, which we show are associated with Hcy export. Although Hcy is the major
      oxidant, cysteine also contributes, as shown by the effect of glutamate. Finally,
      the LDL oxidized in this system showed a time-dependent increase in uptake by
      human macrophages, implying an upregulation of the scavenger receptor. These
      results suggest that continuous export of Hcy from endothelial cells contributes
      to the generation of extracellular hydroxyl radicals, with associated oxidative
      modification of LDL and incorporation into macrophages, a key step in
      atherosclerosis. Factors that regulate intracellular Hcy metabolism modulate
      these effects.

PMID- 15576842
TI  - Effects of silencing leukocyte-type 12/15-lipoxygenase using short interfering
      RNAs.
AB  - The leukocyte-type 12/15-lipoxygenase (12/15-LO) has been implicated in the
      pathogenesis of atherosclerosis, hypertension, and diabetes. 12/15-LO and its
      products are associated with LDL oxidation, cellular growth, migration, adhesion,
      and inflammatory gene expression in monocytes/macrophages, endothelial cells, and
      vascular smooth muscle cells (VSMCs). Our objective, therefore, was to develop
      novel expression vectors for short interfering RNAs (siRNAs) targeting 12/15-LO
      to evaluate its functional relevance in macrophages and VSMCs. We used a PCR
      based approach to rapidly identify effective siRNA target sites on mouse 12/15-LO
      and initially tested their efficacy on a fusion construct of 12/15-LO cDNA and
      enhanced green fluorescent protein. We then cloned these U6 promoter+siRNA PCR
      products into plasmid vectors [short hairpin siRNAs (shRNAs)] to knockdown
      endogenous 12/15-LO expression in mouse macrophages and also rat and mouse VSMCs.
      Furthermore, the functional effects of shRNA-mediated 12/15-LO knockdown were
      noted by the reduced oxidant stress and chemokine [monocyte chemoattractant
      protein-1 (MCP-1)] expression in a differentiated mouse monocytic cell line as
      well as by the reduced cellular adhesion and fibronectin expression in VMSCs.
      Knocking down 12/15-LO expression also reduced the expression of inflammatory
      genes, MCP-1, vascular cell adhesion molecule-1, and interleukin-6 in VSMCs. Our
      results illustrate the functional relevance of 12/15-LO activation in macrophages
      and VSMCs and its relationship to oxidant stress and inflammation.

PMID- 15576843
TI  - Mycobacteria use their surface-exposed glycolipids to infect human macrophages
      through a receptor-dependent process.
AB  - Two subfamilies of the polar glycopeptidolipids (GPLs) located on the surface of
      Mycobacterium smegmatis, along with unknown phospholipids, were recently shown to
      participate in the nonopsonic phagocytosis of mycobacteria by human macrophages
      (Villeneuve, C., G. Etienne, V. Abadie, H. Montrozier, C. Bordier, F. Laval, M.
      Daffe, I. Maridonneau-Parini, and C. Astarie-Dequeker. 2003. Surface-exposed
      glycopeptidolipids of Mycobacterium smegmatis specifically inhibit the
      phagocytosis of mycobacteria by human macrophages. Identification of a novel
      family of glycopeptidolipids. J. Biol. Chem. 278: 51291-51300). As demonstrated
      herein, a phospholipid mixture that derived from the methanol-insoluble fraction
      inhibited the phagocytosis of M. smegmatis. Inhibition was essentially
      attributable to phosphatidylinositol mannosides (PIMs), namely PIM2 and PIM6,
      because the purified phosphatidylethanolamine, phosphatidylglycerol, and
      phosphatidylinositol were inactive. This was further confirmed using purified
      PIM2 and PIM6 from M. bovis BCG that decreased by half the internalization of M.
      smegmatis. Both compounds also inhibited the uptake of M. tuberculosis and M.
      avium but had no effect on the internalization of zymosan used as a control
      particle of the phagocytic process. When coated on latex beads, PIM2 and polar
      GPL (GPL III) favored the particle entry through complement receptor 3. GPL III,
      but not PIM2, also directed particle entry through the mannose receptor.
      Therefore, surface-exposed mycobacterial PIM and polar GPL participate in the
      receptor-dependent internalization of mycobacteria in human macrophages.

PMID- 15576844
TI  - Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I
      induced inhibition of LPL.
AB  - Studies in humans and mice have shown that increased expression of apolipoprotein
      C-I (apoC-I) results in combined hyperlipidemia with a more pronounced effect on
      triglycerides (TGs) compared with total cholesterol (TC). The aim of this study
      was to elucidate the main reason for this effect using human apoC-I-expressing
      (APOC1) mice. Moderate plasma human apoC-I levels (i.e., 4-fold higher than human
      levels) caused a 12-fold increase in TG, along with a 2-fold increase in TC,
      mainly confined to VLDL. Cross-breeding of APOC1 mice on an apoE-deficient
      background resulted in a marked 55-fold increase in TG, confirming that the apoC
      I-induced hyperlipidemia cannot merely be attributed to blockade of apoE
      recognizing hepatic lipoprotein receptors. The plasma half-life of [3H]TG-VLDL
      mimicking particles was 2-fold increased in APOC1 mice, suggesting that apoC-I
      reduces the lipolytic conversion of VLDL. Although total postheparin plasma LPL
      activity was not lower in APOC1 mice compared with controls, apoC-I was able to
      dose-dependently inhibit the LPL-mediated lipolysis of [3H]TG-VLDL-mimicking
      particles in vitro with a 60% efficiency compared with the main endogenous LPL
      inhibitor apoC-III. Finally, purified apoC-I impaired the clearance of [3H]TG
      VLDL-mimicking particles independent of apoE-mediated hepatic uptake in
      lactoferrin-treated mice. Therefore, we conclude that apoC-I is a potent
      inhibitor of LPL-mediated TG-lipolysis.

PMID- 15576845
TI  - Disrupted coordinate regulation of farnesoid X receptor target genes in a patient
      with cerebrotendinous xanthomatosis.
AB  - Cerebrotendinous xanthomatosis (CTX), sterol 27-hydroxylase (CYP27A1) deficiency,
      is associated with markedly reduced chenodeoxycholic acid (CDCA), the most
      powerful activating ligand for farnesoid X receptor (FXR). We investigated the
      effects of reduced CDCA on FXR target genes in humans. Liver specimens from an
      untreated CTX patient and 10 control subjects were studied. In the patient,
      hepatic CDCA concentration was markedly reduced but the bile alcohol level
      exceeded CDCA levels in control subjects (73.5 vs. 37.8 +/- 6.2 nmol/g liver).
      Cholesterol 7alpha-hydroxylase (CYP7A1) and Na+/taurocholate-cotransporting
      polypeptide (NTCP) were upregulated 84- and 8-fold, respectively. However, small
      heterodimer partner (SHP) and bile salt export pump were normally expressed.
      Marked CYP7A1 induction with normal SHP expression was not explained by the
      regulation of liver X receptor alpha (LXRalpha) or pregnane X receptor. However,
      another nuclear receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), was
      induced 2.9-fold in CTX, which was associated with enhanced mRNA levels of
      HNF4alpha target genes, CYP7A1, 7alpha-hydroxy-4-cholesten-3-one 12alpha
      hydroxylase, CYP27A1, and NTCP. In conclusion, the coordinate regulation of FXR
      target genes was lost in CTX. The mechanism of the disruption may be explained by
      a normally stimulated FXR pathway attributable to markedly increased bile
      alcohols with activation of HNF4alpha caused by reduced bile acids in CTX liver.

PMID- 15576846
TI  - Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis
      and enhances collagen deposition.
AB  - Atherosclerosis is a chronic inflammatory disease of the vessel wall
      characterized by the accumulation of lipid-laden macrophages and fibrotic
      material. The initiation of the disease is accompanied by the accumulation of
      modified lipoproteins in the vessel wall. Group IIa secretory phospholipase A2
      (sPLA2 IIa) is a key candidate player in the enzymatic modification of low
      density lipoproteins. To study the role of sPLA2 IIa in macrophages during
      atherogenesis, transgenic mice were generated using the human sPLA2 IIa gene and
      the CD11b promoter. Bone marrow transplantation to LDL receptor-deficient mice
      was performed to study sPLA2 IIa in atherosclerosis. After 10 weeks of high-fat
      diet, mice overexpressing sPLA2 IIa in macrophages showed 2.3-fold larger lesions
      compared with control mice. Pathological examination revealed that sPLA2 IIa
      expressing mice had increased collagen in their lesions, independent of lesion
      size. However, smooth muscle cells or fibroblasts in the lesions were not
      affected. Other parameters studied, including T-cells and cell turnover, were not
      significantly affected by overexpression of sPLA2 IIa in macrophages. These data
      clearly show that macrophage sPLA2 IIa is a proatherogenic factor and suggest
      that the enzyme regulates collagen production in the plaque and thus fibrotic cap
      development.

PMID- 15576847
TI  - Evidence of QTLs on chromosomes 1q42 and 8q24 for LDL-cholesterol and apoB levels
      in the HERITAGE family study.
AB  - Genome-wide multipoint linkage analyses were performed to identify chromosomal
      regions harboring genes influencing LDL-cholesterol, total apolipoprotein B
      (apoB), and LDL-apoB levels using 654 markers. They were assessed in a sedentary
      state (baseline) and after a 20 week endurance training program. Strong evidence
      for two quantitative trait loci (QTLs) for baseline levels was found. There is
      linkage evidence in black families on chromosomes 1q41-q44 [at marker D1S2860,
      238 centimorgan (cM), with a maximum log of the odds (LOD) score of 3.7 for LDL
      apoB] and in white families on chromosome 8q24 (at marker D8S1774, 142 cM, with
      LOD scores of 3.6, 3.3, and 2.5 for baseline LDL-cholesterol, LDL-apoB, and apoB,
      respectively). There were no strong signals for the lipoprotein training
      responses (as computed as the difference in posttraining minus baseline levels).
      In conclusion, QTLs for baseline apoB and LDL-cholesterol levels on chromosomes
      1q41-q44 (in blacks) and 8q24 (in whites) were found. As there are no known
      strong candidate genes in these regions for lipids, follow-up studies to
      determine the source of those signals are needed.

PMID- 15576848
TI  - Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response
      to marked changes in their dietary intake in men.
AB  - We studied the long-chain conversion of [U-13C]alpha-linolenic acid (ALA) and
      linoleic acid (LA) and responses of erythrocyte phospholipid composition to
      variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in
      38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil
      (FXO; 17 g/day ALA, n=21) or sunflower oil (SO; 17 g/day LA, n=17). The FXO diet
      induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid
      (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in
      22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The
      increases in EPA and DPA but not DHA were similar to those in subjects given the
      SO diet enriched with 3 g of EPA plus DHA from fish oil (n=19). The SO diet
      induced a small increase in LA but no change in AA. Long-chain conversion of [U
      13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after
      simple modeling for tracer dilution in subsets from the FXO (n=6) and SO (n=5)
      diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and
      DPA, 0.02%) and varied directly with precursor concentrations and inversely with
      concentrations of fatty acids of the alternative series. [13C]DHA formation was
      very low (<0.01%) with no dietary influences.

PMID- 15576849
TI  - Apple procyanidins decrease cholesterol esterification and lipoprotein secretion
      in Caco-2/TC7 enterocytes.
AB  - Decrease of plasma lipid levels by polyphenols was linked to impairment of
      hepatic lipoprotein secretion. However, the intestine is the first epithelium
      that faces dietary compounds, and it contributes to lipid homeostasis by
      secreting triglyceride-rich lipoproteins during the postprandial state. The
      purpose of this study was to examine the effect of apple and wine polyphenol
      extracts on lipoprotein synthesis and secretion in human Caco-2/TC7 enterocytes
      apically supplied with complex lipid micelles. Our results clearly demonstrate
      that apple, but not wine, polyphenol extract dose-dependently decreases the
      esterification of cholesterol and the enterocyte secretion of lipoproteins. Apple
      polyphenols decrease apolipoprotein B (apoB) secretion by inhibiting apoB
      synthesis without increasing the degradation of the newly synthesized protein.
      Under our conditions, cholesterol uptake, apoB mRNA, and microsomal triglyceride
      protein activity were not modified by apple polyphenols. The main monomers
      present in our mixture did not interfere with the intestinal lipid metabolism. By
      contrast, apple procyanidins reproduced the inhibition of both cholesteryl ester
      synthesis and lipoprotein secretion. Overall, our results are compatible with a
      mechanism of action of polyphenols resulting in impaired lipid availability that
      could induce the inhibition of intestinal lipoprotein secretion and contribute to
      the hypolipidemic effect of these compounds in vivo.

PMID- 15576850
TI  - Indications that paraoxonase-1 contributes to plasma high density lipoprotein
      levels in familial hypercholesterolemia.
AB  - HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against
      oxidative modification in vitro and therefore may protect against cardiovascular
      disease. We investigated the effects of PON1 levels, activity, and genetic
      variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating
      oxidized LDL (OxLDL), subclinical inflammation [high-sensitive C-reactive protein
      (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, -107C/T, 
      162A/G, -824G/A, and -907G/C) were determined in 302 patients with familial
      hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of
      paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were
      determined using an immunoassay. The genetic variants of PON1 that were
      associated with high levels and activity of the enzyme were associated with
      higher HDL-C levels (P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M,
      Q192R, -107C/T, and -907G/C, respectively). In addition to the PON1 genotype,
      there was also a positive correlation between PON1 levels and activity and HDL-C
      (PON1 levels: r = 0.37, P < 0.001; paraoxonase activity: r = 0.23, P = 0.01;
      diazoxonase activity: r = 0.29, P < 0.001; arylesterase activity: r = 0.19, P =
      0.03). Our observations support the hypothesis that both PON1 levels and activity
      preserve HDL-C in plasma.

PMID- 15576851
TI  - Multiplex ligation-dependent probe amplification of LDLR enhances molecular
      diagnosis of familial hypercholesterolemia.
AB  - Autosomal dominant (AD) familial hypercholesterolemia [FH; Mendelian Inheritance
      in Man (MIM) 143890] typically results from mutations in the LDL receptor gene
      (LDLR), which are now commonly diagnosed using exon-by-exon screening methods,
      such as exon-by-exon sequence analysis (EBESA) of genomic DNA (gDNA). However,
      many patients with FH have no LDLR mutation identified by this method. Part of
      the diagnostic gap is attributable to the genetic heterogeneity of AD FH, but
      another possible explanation is inadequate sensitivity of EBESA to detect certain
      mutation types, such as large deletions or insertions in LDLR. Multiplex ligation
      dependent probe amplification (MLPA) is a new method that detects larger gDNA
      alterations that are overlooked by EBESA. We hypothesized that some FH patients
      with no LDLR mutation detectable by EBESA would have an abnormal LDLR MLPA
      pattern. In 70 unrelated FH patients, 44 had LDLR mutations detected by EBESA,
      including missense, RNA splicing, nonsense, or small deletion mutations, and 5
      had the APOB R3500Q mutation. Among the remaining 21 AD FH patients with no
      apparent LDLR mutation, we found abnormal LDLR MLPA patterns in 12 and then
      demonstrated the deleted sequence in 5 of these. These findings indicate that
      MLPA may be a useful new adjunctive tool for the molecular diagnosis of FH.

PMID- 15576852
TI  - Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand
      times lower than reported in multiple sclerosis.
AB  - In a recent publication [Diestel, A., O. Aktas, D. Hackel, I. Hake, S. Meier, C.
      S. Raine, R. Nitsch, F. Zipp, and O. Ullrich. 2003. Activation of microglial poly
      (ADP-ribose)-polymerase-1 by cholesterol breakdown products during
      neuroinflammation: a link between demyelination and neuronal damage. J. Exp. Med.
      198: 1729-1740], extremely high levels of 7-oxocholesterol were reported in
      cerebrospinal fluid (CSF) of 11 patients with multiple sclerosis (MS) [7.4 +/-
      0.3 mg/l (mean +/- SEM)]. The corresponding level of 12 subjects with other kinds
      of neurological diseases was reported to be 0.5 +/- 0.1 mg/l. Such high levels of
      7-oxocholesterol were found to cause neuronal damage of living brain tissues.
      Using a highly accurate method for an assay of 7-oxocholesterol based on isotope
      dilution-mass spectrometry and anaerobic conditions during workup, we found that
      the level of 7-oxocholesterol in CSF from 29 Swedish patients with MS was only
      1.2 microg/l (median, ranging from 0.4 to 4.6 microg/l), less than 1/1,000 th of
      the previously reported level. The level of 7-oxocholesterol in CSF from 24
      Swedish control patients was 0.9 microg/l (0.3-2.3 microg/l), slightly but
      significantly lower than the CSF level in MS patients (P=0.002). In vitro-induced
      lipid peroxidation of the endogenous cholesterol in CSF increased the level of 7
      oxygenated cholesterol metabolites, particularly 7-oxocholesterol, up to
      approximately 0.3 mg/l. These results are discussed in relation to the fact that
      7-oxygenated steroids are easily artificially formed by autoxidation of
      cholesterol during workup procedures and analysis of sterols and oxysterols from
      biological samples.

PMID- 15576853
TI  - Age differences in emotion-regulation strategies in handling everyday problems.
AB  - We examined age differences in problem-focused and emotion-regulatory problem
      solving strategy use for self-generated family problems. Young, middle-aged, and
      older participants generated family problem situations that were high and low in
      emotional salience. They were asked both how they solved the problem and how they
      managed emotions involved in the problem. We conducted analyses on three
      categories of problem-solving strategies: instrumental strategies, proactive
      emotion regulation, and passive emotion regulation. When regulating emotions,
      middle-aged adults used more proactive emotion-regulation strategies than older
      adults, and older adults used more passive emotion-regulation strategies than
      middle-aged adults. These effects were driven by the high emotional salience
      condition.

PMID- 15576854
TI  - Change in depressive symptoms in the Baltimore longitudinal study of aging.
AB  - Depressive symptoms have been represented in the research and clinical literature
      in terms of both an episodic phenomenon and as enduring individual differences.
      We investigated depressive symptoms longitudinally in a sample of older adults.
      Participants were 737 individuals (M(Age) = 73 years initially, 39% women) in the
      Baltimore Longitudinal Study of Aging who provided biennial Center for
      Epidemiological Studies-Depression data on up to five occasions over an 8-year
      period. We found both trait and state-residual variability, with symptoms
      increasing longitudinally on all subscales and accounting for an approximately 1
      point increase per decade. Trait-like variability accounted for at least two
      thirds of the reliable variance. Interindividual differences were consistent over
      time, but occasion-specific variability diminished across occasions.

PMID- 15576855
TI  - Social network characteristics and cognition in middle-aged and older adults.
AB  - We examined the relationship between social network characteristics and global
      cognitive status in a community-based sample of 354 adults aged 50+ and with Mini
      Mental State Examination (MMSE) scores of 28+ at baseline. Multivariate analyses
      indicated that interaction in larger social networks related to better
      maintenance of MMSE scores and reduced odds of decline to population-based lower
      quartile MMSE scores at follow-up 12 years later. At follow-up, higher levels of
      interpersonal activity (more frequent contacts in larger social networks) and
      exposure to emotional support independently related positively to MMSE. The
      findings suggest that interaction in larger social networks is a marker that
      portends less cognitive decline, and that distinct associational paths link
      interpersonal activity and emotional support to cognitive function.

PMID- 15576856
TI  - Aging and memory for self-performed tasks: effects of task difficulty and time
      pressure.
AB  - An increase in task difficulty or time pressure during the performance of
      cognitive tasks decreased the ability of older adults to recall the tasks. In
      Experiments 1 and 2, adult age differences in recall of cognitive tasks were
      smaller for easier than for more difficult tasks, and, in Experiment 3, adult age
      differences were smaller for recall of cognitive tasks without time pressure than
      for recall of cognitive tasks with time pressure. During difficult or time
      pressured cognitive tasks, older adults may become anxious about their
      performance, and they may have trouble inhibiting negative self-evaluative
      thoughts about their performance. Older adults may thus devote less attention to
      aspects of the cognitive tasks that would be beneficial for task recall.

PMID- 15576857
TI  - Structural modeling of dynamic changes in memory and brain structure using
      longitudinal data from the normative aging study.
AB  - This is an application of new longitudinal structural equation modeling
      techniques to time-dependent associations of memory and brain structure
      measurements. There were 225 participants aged 30-80 years at baseline who were
      measured again after a 7-year interval on both the lateral ventricular size and
      Wechsler memory score. Multiple regression analyses show nonlinear associations
      with age but no relationships among longitudinal changes. Mixed-effects latent
      growth curve analyses and analyses based on latent difference scores indicate
      that longitudinal changes in both variables are reasonably well described by an
      exponential or dual change model. Bivariate dynamic structural equation modeling
      analyses indicate age-lagged changes operate in a coupled-over-time fashion, with
      the brain measure (lateral ventricular size) as a leading indicator in time of
      memory (Wechsler memory score) declines.

PMID- 15576858
TI  - An evaluation of performance by older persons on a simulated telecommuting task.
AB  - Telecommuting work represents a strategy for managing the growing number of older
      people in the workforce. This study involved a simulated customer service
      telecommuting task that used e-mail to answer customer queries about media
      related products and company policies. Participants included 27 "younger" older
      adults (50-65 years) and 25 "older" older adults (66-80 years). The participants
      performed the task for two 2-hr sessions a day over 4 consecutive days. Although
      both age groups showed significant improvement across sessions on many of the
      performance criteria, in general the improvements were more marked for the older
      age-group participants. However, the participants from both age groups had
      difficulty meeting some of the task performance requirements. These results are
      discussed in terms of training strategies for older workers.

PMID- 15576859
TI  - Explicit contamination contributes to aging effects in episodic priming:
      behavioral and ERP evidence.
AB  - We examined the impact of explicit contamination on age-related changes in
      episodic priming. We recorded event-related brain potentials (ERPs) from older
      and younger adults to primed and unprimed nouns tested in a recognition memory
      task. Results revealed that the magnitude of priming was greater in the younger
      adults. ERPs revealed a priming effect in the younger adults that was absent in
      older adults. Findings suggest that explicit contamination may account for the
      reported aging effect: Item memory was correlated with episodic priming and ERP
      priming in younger adults, but not older adults; item memory was associated with
      episodic priming after aging effects were controlled for; and the topographies of
      the young's priming and item memory effects were indistinguishable. Given the
      apparent vulnerability to contamination by explicit memory, we suggest caution
      when researchers use an episodic priming paradigm to assess aging effects in
      implicit memory.

PMID- 15576860
TI  - Are there any concerns about gender inclusion?

PMID- 15576861
TI  - Feminist gerontology and old men.
AB  - This article outlines feminist gerontology and shows how its focus on power
      relations lends insight into the lives of those people disadvantaged by them as
      well as the people privileged by social inequalities. To illustrate the latter, I
      discuss how feminist gerontology might examine old men, using the topic of health
      as an example. For instance, arrangements that maintain privilege in young
      adulthood and middle age can lead to poor health in old age. These practices of
      masculinity include physical risk in competition with other men, neglect of
      social networks and medical care, and avoidance of any self-report of emotional
      strain. However, with its focus on diversity, feminist gerontology also
      emphasizes that experiences of manhood, aging, and health vary by one's location
      in a network of inequalities.

PMID- 15576862
TI  - Economic status in later life among women who raised children outside of
      marriage.
AB  - OBJECTIVE: Many single mothers are likely to face special economic challenges in
      old age, because they often have limited employment histories and cannot rely on
      husbands for financial support. This article examines the economic status of
      these women in later life. METHODS: The analysis uses nationally representative
      data from the Health and Retirement Study to estimate multivariate models of
      income, assets, and poverty rates for women aged 65-75 in 1999. RESULT:
      Controlling for education, current marital status, and race and ethnicity, the
      models indicate that women who spent > or =10 years raising dependent children
      outside of marriage are 55% more likely to live in poverty at ages 65-75 than
      women who were always married when their children were young. DISCUSSION: The
      financial difficulties confronting single mothers raising children persist into
      later life. Social Security reforms, especially those that are not tied to the
      current system of spousal and survivor benefits, could improve retirement
      security for these vulnerable women, whose numbers will begin to soar when the
      many women who raised children outside of marriage in the 1970s retire in coming
      years.

PMID- 15576863
TI  - Negotiating care: ties between aging mothers and their caregiving daughters.
AB  - OBJECTIVE: Using a feminist social constructionist perspective, we illuminate how
      aging mothers and their caregiving daughters negotiate issues of connection,
      autonomy, and conflict. METHODS: We conducted a qualitative analysis of
      videotaped interactions between 31 White mother-daughter pairs. RESULT: We found
      that the mothers and daughters mostly (a) were attentive and responsive, (b)
      preserved mothers' autonomy, and (c) minimized open conflict and tension. Subtle
      behavioral cues visible on the videotapes also exposed underlying emotional
      tension in these relationships. These cues alerted us to important variation in
      relationship quality among the pairs. Three patterns of relating emerged: (a)
      symmetrically connected, (b) asymmetrically connected, and (c) symmetrically
      constrained. DISCUSSION: Our exploratory study suggests that a balance between
      autonomy and connection is fundamental to the success of these mother-daughter
      caregiving relationships. Not only is it important for frail mothers to be
      responsive to their caregiving daughter's needs, but also it is important for
      daughters to support the autonomy and independence of their mothers. Our study
      also highlights the importance of attentiveness in these relationships. Even when
      mothers, because of illness and frailty, were less capable of attending to their
      daughters' lives, daughters in connected pairs interacted with their mothers in
      attentive ways. In constrained pairs, neither intergenerational partner was
      attentive.

PMID- 15576864
TI  - Retirement transitions and spouse disability: effects on depressive symptoms.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of type of
      retirement (forced, early, abrupt) and spouse's disability on longitudinal change
      in depressive symptoms. METHODS: The analyses rely on Waves 1-4 of the Health and
      Retirement Survey (N = 2,649). Generalized estimating equations models with
      bootstrapped standard errors and adjustment for survey design and non
      independence of dyad members estimate effects of retirement, type of retirement,
      and spouse's disability on depressive symptoms, controlling for relevant
      covariates. RESULTS: The results suggest that depressive symptoms increase when
      retirement is abrupt and perceived as too early or forced. Women retirees who
      stopped employment and were either forced into retirement or perceived their
      retirement as too early report significantly more depressive symptoms with
      increasing spouse activities of daily living (ADLs) limitations. There is no
      similar effect for men. In contrast, for working retirees who retired on time,
      depressive symptoms decrease with increasing spouse ADLs. DISCUSSION: These
      results highlight the importance of retirement context on postretirement well
      being. They suggest that both type of retirement transition and marital contexts
      such as spouse's disability influence postretirement well-being, and these
      effects differ by gender.

PMID- 15576865
TI  - The transition to widowhood and the social regulation of health: consequences for
      health and health risk behavior.
AB  - OBJECTIVES: This study estimates the effects of the transition to widowhood on
      changes in the social regulation of health and examines the consequences of this
      association for health and health risk behavior following spousal death. METHODS:
      Analysis of longitudinal data from the Changing Lives of Older Couples Study
      tests the following hypotheses: (a) Widowed individuals experience greater
      declines in health regulation over time than their married counterparts and (b)
      the extent to which widowhood undermines health and increases health risk
      behavior depends on whether it is accompanied by a decline in health regulation.
      RESULTS: Compared with their continually married counterparts, those who
      experience the transition to widowhood report a significant decline in the
      frequency of health reminders and health assistance received from others. The
      decline in the frequency of health regulation has important consequences for
      health behavior and health outcomes. Widowhood undermines health and increases
      health risk behaviors only when it is accompanied by a decline in health
      regulation. Widowed individuals who experience increases in health regulation
      show improvements in health and declines in health risk behavior. DISCUSSION:
      Interventions targeted at improving the health habits of widowed individuals by
      mobilizing health-related support systems may be effective at minimizing the
      negative health consequences of spousal loss.

PMID- 15576866
TI  - Stability and change in the perceived social support of older Taiwanese adults.
AB  - OBJECTIVE: The purpose of this study is to examine stability and change in
      Taiwanese elders' perceptions about the availability of social support and the
      sociodemographic and cultural factors associated with change. METHODS: This study
      uses data from four waves of the Survey of Living Status of the Elderly in Taiwan
      that spans a 10-year period and employs latent growth curve models to examine
      trajectories of perceived support and the sociocultural factors that may explain
      variability in baseline levels of support and variability in changes in support
      as respondents age. RESULT: Perceptions about social support appear to follow a
      linear trajectory across age, with significant variation in baseline perceptions
      and in patterns of change in perceived support across the sample. Sociocultural
      factors primarily explain differences in initial levels of support but also have
      some effect on changes in support. DISCUSSION: Despite the increasing pressures
      and demands on adult children's time that are associated with social and economic
      development, the elderly in Taiwan on average feel supported by their social
      networks, with the perceived availability of support increasing with age.

PMID- 15576867
TI  - Decision-making process for those in later life who are downsizing their
      residences.

PMID- 15576869
TI  - Use of sensorineural tests in a large volume of medico-legal compensation claims
      for HAVS.
AB  - BACKGROUND: The Department of Trade and Industry set up a contract to examine
      miners and ex-miners claiming compensation for hand-arm vibration syndrome
      (HAVS). They had been exposed to hand-transmitted vibration. Over 100,000 have
      now been examined using sensorineural tests as part of that process. AIMS: The
      purpose of this paper was to examine the internal consistency of the vibrotactile
      threshold test (VTT) and the thermal aesthesiometry test (TA). METHODS: In 18
      centres across the UK, nurses were trained to perform the measurement of VTT and
      TA in a controlled standardized manner. These tests were to aid the staging of
      the neurological component of the Stockholm Workshop Scales. The staging of this
      component was modified by dividing stage 2SN into 2SN (early) and 2SN (late). The
      test results and an automatic neurological staging were presented to the
      examining doctor following the clinical examination. The results of these
      sensorineural tests were held on a central database. The results and analysis of
      the first 57,000 tests are reported. RESULTS: The correlations within the VTT and
      TA scores were consistent with reliable measures. However, these correlations
      were not of such strength as to allow reliance on the results of a single test
      when making an assessment of the severity of neurological damage. CONCLUSIONS:
      Different end organs and nerve fibres should be tested when making an assessment
      of damage in the sensorineural component of HAVS. The correlations demonstrated
      for the VTT and TA suggest that they are of value in assessing these claimants
      and would be for other vibration exposed workers.

PMID- 15576870
TI  - Dog noise as a risk factor for hearing loss among police dog handlers.
AB  - AIM: To determine the sources of noise exposure among police dog handlers and to
      examine whether these levels might lead to noise-induced hearing loss. METHODS:
      We conducted a cross-sectional study at four Royal Air Force bases using a noise
      survey, a postal questionnaire and medical record review. The noise survey was
      conducted following task analysis. We surveyed police dog handlers and a
      comparison group of police who had never been dog handlers, using a postal
      questionnaire on noise exposures and confounders. Audiometric and otological data
      were extracted from medical records. RESULTS: The noise survey revealed
      significant exposures due to dogs, travelling in vans and aircraft noise during
      foot patrol. The overall response rate to the questionnaire was 56% (29 police
      dog handlers, 24 police officers). Five subjects (9.4%) had age-corrected hearing
      loss exceeding 10 dB, averaged over the 4 and 6 kHz frequencies, affecting the
      left ear only, but there were no differences between dog handlers and controls.
      CONCLUSION: Although the measured noise exposures of police dog handlers did not
      exceed current legal limits, the noise levels at times are such that the proposed
      Physical Agents (Noise) Directive has implications for employers who use dogs for
      security purposes.

PMID- 15576871
TI  - Evaluation of potential reduction in blood and body fluid exposures by use of
      alternative instruments.
AB  - BACKGROUND: Injuries from needlestick, sharps injuries and splashes lead to
      exposure to blood and body fluids with the potential for transmission of blood
      borne viruses. AIMS: To identify alternative instruments, which if used would
      improve worker safety. METHODS: Retrospective review of 161 injuries with
      identification of safer alternative products for instruments that caused injury.
      The proportion of injuries that could be prevented was calculated [with 95%
      confidence intervals (CI)]. RESULTS: The average rate of injury was 7.8/1000
      employees per annum (95% CI, 6.8-9.4/1000). In the 2 years the highest rates of
      injury occurred in pre-registration house officers (164/1000; 95% CI, 64
      264/1000), phlebotomists (154/1000; 95% CI, 15-291/1000) and senior house
      officers (45/1000; 95% CI, 13-77/1000). An upper estimate of 65% (95% CI, 58-72%)
      of incidents would have been preventable with a change to alternative devices.
      CONCLUSIONS: Change to the use of intrinsically safer instrumentation has the
      potential to prevent injury to healthcare workers.

PMID- 15576872
TI  - Characteristics of an external employee assistance programme in Japan.
AB  - BACKGROUND: Mental health care is now a major occupational health issue in Japan.
      Although realizing effective use of external employee assistance programmes
      (EAPs) has been identified as crucial for mental health care, few scientific
      papers describe or analyse the characteristics of EAPs in Japan. AIMS: This study
      sought to clarify the characteristics of an external EAP in Japan. METHODS: The
      characteristics of an external EAP were clarified in terms of programme
      description and utilization. A total of 10,260 counselling sessions from 1996 to
      2000 were used for utilization analysis. RESULTS: The EAP studied had contracts
      with 133 organizations, half of which were health insurance societies. The EAP
      provided employees and family members with free, confidential counselling. Annual
      mean utilization rate per 1000 individuals increased from 1.3 in 1996 to 2.7 in
      2000. Less than one-third of counselling sessions were for work-related mental
      health issues, and male users (30%) consulted significantly more often than
      female users (14%) for such problems. Among men, career development issues were
      most common, while job dissatisfaction was highest among women. Absenteeism,
      depression and fatigue were the most frequently observed problems in both sexes.
      CONCLUSIONS: EAP use in Japan is rising. The majority of its use is for non-work
      related health issues. Male users were more likely to consult for work-related
      mental health problems.

PMID- 15576873
TI  - Evaluation of a multidisciplinary treatment for patients with chronic non
      specific upper-limb musculoskeletal disorders: a pilot study.
AB  - BACKGROUND: Upper-limb musculoskeletal disorders (ULMSDs) are considered a major
      health and socio-economic problem. However, knowledge about the effect of
      treatment programmes is scarce. Objective To evaluate the effect of a
      multidisciplinary treatment programme on well-being, disability and return to
      work in patients with chronic non-specific upper-limb disorders. METHODS: A
      longitudinal and uncontrolled design with pre-post measurements was used. Forty
      one patients on long-term sick leave attended for multidisciplinary treatment
      aimed at training in personal coping strategies and improving activities of daily
      living. Outcome measures were generic well-being (SF-36), disability (DASH) and
      return to work (working hours). RESULTS: General well-being improved
      significantly between pre-treatment and post-treatment. Level of disability
      declined significantly between pre-treatment and post-treatment. In 63% of the
      patients, return to own work was complete at follow up, 4 months post-treatment.
      CONCLUSION: The results of this uncontrolled intervention study suggest that
      multidisciplinary treatment programmes improve general well-being, reduce
      disability and facilitate return to work in patients with chronic non-specific
      ULMSDs.

PMID- 15576874
TI  - Musculoskeletal complaints and psychosocial risk factors among Chinese hospital
      nurses.
AB  - BACKGROUND: Musculoskeletal complaints represent a common occupational problem
      for health care workers throughout the world. Despite their sizeable numbers,
      however, few epidemiological studies have investigated musculoskeletal complaints
      among Chinese hospital nurses. Objective To assess the prevalence of, and risk
      factors for, musculoskeletal complaints among hospital nurses in mainland China.
      METHODS: A total of 282 female, registered nurses were surveyed (92% response
      rate) using a modified Chinese-language version of the Standardized Nordic
      Questionnaire. Body sites were divided into the neck, shoulder, upper back and
      lower back regions. RESULTS: The 12 month period-prevalence of musculoskeletal
      complaints at any of the four regions was 70%. The lower back was the most
      commonly reported body site (56%), followed by the neck (45%), shoulder (40%) and
      upper back (37%). High mental pressure, boring or tedious tasks and limited work
      support were identified as significant risk factors (adjusted odds ratios: 1.79
      2.52). No correlations were found between manual handling or perceived physical
      exertion and increased reporting of musculoskeletal complaints. CONCLUSION: This
      study has shown that musculoskeletal complaints are prevalent among Chinese
      hospital nurses. The correlation with various psychosocial factors is also
      consistent with evidence from other countries.

PMID- 15576875
TI  - Hearing Surveillance Chart--a tool for tracking serial audiometry results and
      predicting future hearing impairment.
AB  - High frequency hearing loss is related to noise-induced deafness. We decided to
      develop a method of recording serial audiogram results that would provide an
      accessible overview of trends for an individual. Health & Safety Executive (HSE)
      warning and referral levels for high frequency hearing losses were plotted
      against age. A third line was added to indicate a level of 'significant'
      handicap. This graph is inserted in each individual's hearing surveillance
      record. High frequency hearing loss results are plotted for each ear over time.
      Someone with known hearing loss but minimal deterioration will exceed the HSE
      warning level at every review, whereas someone with perfect hearing suffering a
      significant deterioration may not exceed the warning level initially. The latter
      should be of more concern to their current employer.

PMID- 15576876
TI  - Self-rated health in a population of expatriate workers and partners in Riyadh,
      Saudi Arabia.
AB  - BACKGROUND: Anthropological theory suggests that expatriate workers progress
      through a sequence of adaptive stages during their adjustment to a new
      environment. The psychological and physiological effects of this adaptation
      process may be reflected in changes in self-rated general health. AIMS: To
      explore the relationship between self-rated general health, duration of
      expatriate assignment and two health-related behaviours: physical exercise and
      cigarette smoking. METHOD: A self-administered questionnaire recorded the
      demographics, self-rated general health, exercise and smoking behaviours of the
      adult non-Saudi residents of an expatriate compound in Riyadh, Saudi Arabia.
      RESULTS: The mean self-rated general health of the study group was better than
      comparable UK and New Zealand population norms. Self-rated general health was not
      associated with duration of assignment, but was associated with physical
      exercise, including a dose-response effect. Middle Eastern expatriates had lower
      self-rated health scores and a higher prevalence of cigarette smoking than other
      expatriates. CONCLUSIONS: While the sampling frame limits generalization,
      physical exercise may promote expatriates' general health. Middle Eastern
      expatriates may be a target group for smoking health education.

PMID- 15576877
TI  - The interpretation of zinc protoporphyrin changes in lead intoxication: a case
      report and review of the literature.
AB  - BACKGROUND: Zinc protoporphyrin (ZPP) has been used both as a screening and
      diagnostic test for overexposure to lead for nearly 30 years, although
      limitations for both purposes are recognized. METHODS: We present longitudinal
      findings for ZPP and whole-blood lead in a man with two episodes of acute lead
      intoxication and review the literature on the use of ZPP. RESULTS AND
      CONCLUSIONS: ZPP elevations in both chronic and acute exposure settings lag
      behind elevations in whole-blood lead by approximately 8-12 weeks. Therefore, ZPP
      measurement, in conjunction with whole-blood lead determination, has clinical
      utility in cases of substantial overexposure by providing information on how long
      an individual may have been overexposed to lead. A guide to the interpretation of
      various combinations of whole-blood lead and ZPP results is provided. However,
      while ZPP levels do correlate with whole-blood lead measurements in aggregate,
      the considerable individual variability of ZPP measurements, poor sensitivity at
      lower ranges of lead exposure, poor specificity and delayed changes in unstable
      exposure conditions indicate that this test contributes little to screening
      programs. Finally, our results confirm that basophilic stippling is seen in acute
      as well as chronic lead intoxication, and may provide the first indication of
      lead intoxication.

PMID- 15576878
TI  - Hepatitis B immunity in medical students.

PMID- 15576879
TI  - Monitor. Coronary heart disease.

PMID- 15576882
TI  - The role of sleep in changing our minds: a psychologist's discussion of papers on
      memory reactivation and consolidation in sleep.
AB  - The group of papers on memory reactivation and consolidation during sleep
      included in this volume represents cutting edge work in both animals and humans.
      They support that the two types of sleep serve different necessary functions. The
      role of slow wave sleep (SWS) is reactivation of the hippocampal-neocortical
      circuits activated during a waking learning period, while REM sleep is
      responsible for the consolidation of this new learning into long-term memory.
      These studies provide further insights into mechanisms involved in brain
      plasticity. Robeiro has demonstrated the upregulation of an immediate-early gene
      (IEG zif 268) to waking levels, which occurs only in REM and only in connection
      with new learning. McNaughton and his group have identified electrical indicators
      that the hippocampus and neocortex are talking to each other by testing the
      coactivation of hippocampal sharp wave bursts in SWS and shifts from down to up
      states of activation in the neocortex. In human studies Smith's group reports
      work on individual differences such as intelligence and presleep alcohol that
      affect postsleep performance, and Stickgold and collaborators report that a short
      nap will improve performance if it contains REM sleep. Payne and Nadel suggest
      that the recall benefit associated with REM sleep may be due to its association
      with increased cortisol levels. These papers are important not only in their
      individual contributions but also in revitalizing the work coordinating waking
      and sleep. This promises to further the understanding of how our unique capacity
      to learn from experience and modify our behavior takes place.

PMID- 15576883
TI  - Memory reactivation and consolidation during sleep.
AB  - Do our memories remain static during sleep, or do they change? We argue here that
      memory change is not only a natural result of sleep cognition, but further, that
      such change constitutes a fundamental characteristic of declarative memories. In
      general, declarative memories change due to retrieval events at various times
      after initial learning and due to the formation and elaboration of associations
      with other memories, including memories formed after the initial learning
      episode. We propose that declarative memories change both during waking and
      during sleep, and that such change contributes to enhancing binding of the
      distinct representational components of some memories, and thus to a gradual
      process of cross-cortical consolidation. As a result of this special form of
      consolidation, declarative memories can become more cohesive and also more
      thoroughly integrated with other stored information. Further benefits of this
      memory reprocessing can include developing complex networks of interrelated
      memories, aligning memories with long-term strategies and goals, and generating
      insights based on novel combinations of memory fragments. A variety of research
      findings are consistent with the hypothesis that cross-cortical consolidation can
      progress during sleep, although further support is needed, and we suggest some
      potentially fruitful research directions. Determining how processing during sleep
      can facilitate memory storage will be an exciting focus of research in the coming
      years.

PMID- 15576884
TI  - Sleep, dreams, and memory consolidation: the role of the stress hormone cortisol.
AB  - We discuss the relationship between sleep, dreams, and memory, proposing that the
      content of dreams reflects aspects of memory consolidation taking place during
      the different stages of sleep. Although we acknowledge the likely involvement of
      various neuromodulators in these phenomena, we focus on the hormone cortisol,
      which is known to exert influence on many of the brain systems involved in
      memory. The concentration of cortisol escalates over the course of the night's
      sleep, in ways that we propose can help explain the changing nature of dreams
      across the sleep cycle.

PMID- 15576885
TI  - Declarative memory consolidation: mechanisms acting during human sleep.
AB  - Of late, an increasing number of studies have shown a strong relationship between
      sleep and memory. Here we summarize a series of our own studies in humans
      supporting a beneficial influence of slow-wave sleep (SWS) on declarative memory
      formation, and try to identify some mechanisms that might underlie this
      influence. Specifically, these experiments show that declarative memory benefits
      mainly from sleep periods dominated by SWS, whereas there is no consistent
      benefit of this memory from periods rich in rapid eye movement (REM) sleep. A
      main mechanism of declarative memory formation is believed to be the reactivation
      of newly acquired memory representations in hippocampal networks that stimulates
      a transfer and integration of these representations into neocortical neuronal
      networks. Consistent with this model, spindle activity and slow oscillation
      related EEG coherence increase during early sleep after intense declarative
      learning in humans, signs that together point toward a neocortical reprocessing
      of the learned material. In addition, sleep seems to provide an optimal milieu
      for declarative memory reprocessing and consolidation by reducing cholinergic
      activation and the cortisol feedback to the hippocampus during SWS.

PMID- 15576887
TI  - Hippocampal sharp wave bursts coincide with neocortical "up-state" transitions.
AB  - The sleeping neocortex shows nested oscillatory activity in different frequency
      ranges, characterized by fluctuations between "up-states" and "down-states." High
      density neuronal ensemble recordings in rats now reveal the interaction between
      synchronized activity in the hippocampus and neocortex: Electroencephalographic
      sharp waves in the hippocampus were more probable during down-states than during
      up-states, and tended to coincide with transitions from down-states to up-states.
      The form of cortical activity fluctuations and their interactions with sharp
      waves depend on sleep depth: In deeper sleep stages, characterized by strong
      neocortical oscillation in the delta range or slower (approximately 0.8-4 Hz),
      sharp-wave-triggered peri-event time histograms (PETH) are consistent with a
      longer duration for down-states than for up-states. In lighter sleep, the sharp
      wave-triggered PETH suggested longer up-states than down-states. These results
      highlight the interplay in the hippocampal/neocortical loop: Decreased
      neocortical input during down-states may be a factor in generation of sharp
      waves. In turn, sharp waves may facilitate down-to-up transitions. This interplay
      may reflect joint memory trace reactivation in the hippocampus and in the
      neocortex, possibly contributing to consolidation of long-term memory: Off-line
      reactivation of recent neural activity patterns in the hippocampus occurs during
      50-100-msec electroencephalographic sharp waves, corresponding to pyramidal-cell
      population bursts. The neocortical up-states starting in correspondence with
      sharp waves may be influenced by the reactivated information carried by the
      hippocampal sharp wave.

PMID- 15576886
TI  - Reverberation, storage, and postsynaptic propagation of memories during sleep.
AB  - In mammals and birds, long episodes of nondreaming sleep ("slow-wave" sleep, SW)
      are followed by short episodes of dreaming sleep ("rapid-eye-movement" sleep,
      REM). Both SW and REM sleep have been shown to be important for the consolidation
      of newly acquired memories, but the underlying mechanisms remain elusive. Here we
      review electrophysiological and molecular data suggesting that SW and REM sleep
      play distinct and complementary roles on memory consolidation: While
      postacquisition neuronal reverberation depends mainly on SW sleep episodes,
      transcriptional events able to promote long-lasting memory storage are only
      triggered during ensuing REM sleep. We also discuss evidence that the wake-sleep
      cycle promotes a postsynaptic propagation of memory traces away from the neural
      sites responsible for initial encoding. Taken together, our results suggest that
      basic molecular and cellular mechanisms underlie the reverberation, storage, and
      propagation of memory traces during sleep. We propose that these three processes
      alone may account for several important properties of memory consolidation over
      time, such as deeper memory encoding within the cerebral cortex, incremental
      learning several nights after memory acquisition, and progressive hippocampal
      disengagement.

PMID- 15576888
TI  - Sleep-dependent learning and motor-skill complexity.
AB  - Learning of a procedural motor-skill task is known to progress through a series
      of unique memory stages. Performance initially improves during training, and
      continues to improve, without further rehearsal, across subsequent periods of
      sleep. Here, we investigate how this delayed sleep-dependent learning is affected
      when the task characteristics are varied across several degrees of difficulty,
      and whether this improvement differentially enhances individual transitions of
      the motor-sequence pattern being learned. We report that subjects show similar
      overnight improvements in speed whether learning a five-element unimanual
      sequence (17.7% improvement), a nine-element unimanual sequence (20.2%), or a
      five-element bimanual sequence (17.5%), but show markedly increased overnight
      improvement (28.9%) with a nine-element bimanual sequence. In addition,
      individual transitions within the motor-sequence pattern that appeared most
      difficult at the end of training showed a significant 17.8% increase in speed
      overnight, whereas those transitions that were performed most rapidly at the end
      of training showed only a non-significant 1.4% improvement. Together, these
      findings suggest that the sleep-dependent learning process selectively provides
      maximum benefit to motor-skill procedures that proved to be most difficult prior
      to sleep.

PMID- 15576889
TI  - Posttraining increases in REM sleep intensity implicate REM sleep in memory
      processing and provide a biological marker of learning potential.
AB  - Posttraining rapid eye movement (REM) sleep has been reported to be important for
      efficient memory consolidation. The present results demonstrate increases in the
      intensity of REM sleep during the night of sleep following cognitive
      procedural/implicit task acquisition. These REM increases manifest as increases
      in total number of rapid eye movements (REMs) and REM densities, whereas the
      actual time spent in REM sleep did not change. Further, the participants with the
      higher intelligence (IQ) scores showed superior task acquisition scores as well
      as larger posttraining increases in number of REMs and REM density. No other
      sleep state changes were observed. None of the pretraining baseline measures of
      REM sleep were correlated with either measured IQ or task performance.
      Posttraining increases in REM sleep intensity implicate REM sleep mechanisms in
      further off-line memory processing, and provide a biological marker of learning
      potential.

PMID- 15576890
TI  - Understanding and resolving adherence problems.
AB  - The expert panel report version 2 (EPR-2) is a comprehensive set of
      recommendations for the evaluation and treatment of asthma. However, physicians
      demonstrate scant adoption of many of the key evaluation and treatment components
      of the EPR-2, with primary care physicians being less likely to adopt EPR-2
      recommendations than specialist physicians. Patients also demonstrate very
      limited adoption of physician recommendations, such as the use of medications as
      prescribed. Predictors of physician and patient nonadherence are reviewed, as
      modifiable predictors may be targets for interventions to enhance adherence.
      Finally, areas for future efforts are identified.

PMID- 15576891
TI  - Immunotherapy in the age of anti-IgE.
AB  - Recent results of allergen immunotherapy research have continued to validate
      efficacy and have also demonstrated a truly preventive aspect for this treatment.
      This review summarizes the basic principles of effective allergen immunotherapy
      and highlights some of the advances that have been published in the past year.
      These studies show that allergen immunotherapy, when done appropriately and
      properly, not only causes a decrease in symptoms and use of medication as well as
      an improved quality of life, but that the progression of disease from allergic
      rhinitis to asthma is substantially decreased and the development of new
      allergies is diminished. In addition, laboratory studies continue to demonstrate
      significant changes in the immune system with a shift in the immune pathway from
      TH2 toward a TH1 response. The impact of anti-IgE as a therapeutic agent with
      allergen immunotherapy is also be reviewed.

PMID- 15576892
TI  - Clinical immunology in practice, new opportunities.
AB  - While research provides new opportunities for diagnosing and treating patients
      with allergic and immunological disorders, there are significant challenges to
      putting these advances into use in clinical practice. Each new test may require
      clinicians in private practice to battle with a health insurer's designated
      clinical laboratory in an effort to get this new test and other accurate
      immunological laboratory studies. A new test may or may not be covered by some
      health care plans and may or may not be available from their designated
      laboratories. Many of these laboratories send time-sensitive samples across the
      country with risk of time delays and poor specimen handling leading to inaccurate
      results and/or the need to send repeat specimens. The growing role of managed
      care in every medical decision has led to frustrations for the patient and
      physician. This frequently requires a consult at a tertiary care center, where
      laboratory studies may be more easily accessible with fewer restrictions. Where
      are the new opportunities? Some are found in the enhanced ability to make
      intelligent decisions in the diagnosis and treatment of immunological diseases.
      There is now a greater selection and availability of intravenous gamma-globulin
      (IVIG), that can be matched to individual patient needs. The appropriate
      selection of these products will decrease adverse reactions and increase safety.
      There was a major advance in the treatment of moderate and severe asthma with the
      addition of omalizumab therapy. It provides allergists and immunologists with
      their first monoclonal humanized anti-IgE antibody.

PMID- 15576893
TI  - Defining complementary and alternative medicine in allergies and asthma: benefits
      and risks.
AB  - In this review, the current literature discussing complementary/alternative
      medicine (CAM) interventions, the prevalence and pattern of use, examples of
      specific modalities and the risks of CAM for asthma and atopic disease are
      discussed. The specific risks of CAM interventions associated with the use of
      these modalities, omission of traditional therapeutic modalities, and the
      liability risk for physicians who either provide or counsel their patients
      regarding CAM interventions are also discussed.

PMID- 15576894
TI  - Food allergy: opportunities and challenges in the clinical practice of allergy
      and immunology.
AB  - Food allergy offers numerous opportunities and challenges for the allergy and
      clinical immunology specialist. Physicians with board certification in allergy
      and clinical immunology should be the main source of reliable clinical
      information to educate patients with food-related disorders. There has been a
      wealth of reliable information published related to food allergy that can be
      utilized by health care providers in clinical practice. This includes information
      about the cross-reactivity of food allergens, the evaluation of potential new
      therapies, and the practical application of new diagnostic methods and management
      strategies. This article addresses some of the new developments in food allergy,
      with an emphasis on cross-reactvity of food allergens, recombinant food
      allergens, and potential future therapies for food allergy.

PMID- 15576895
TI  - Interfacing computers and the internet with your allergy practice.
AB  - Computers and the internet have begun to play a prominent role in the medical
      profession and, in particular, the allergy specialty. Computer technology is
      being used more frequently for patient and physician education, asthma management
      in children and adults, including environmental control, generating patient
      databases for research and clinical practice and in marketing and e-commerce.
      This article will review how computers and the internet have begun to interface
      with the allergy subspecialty practice in these various areas.

PMID- 15576896
TI  - The allergy and immunology specialist: what is the role in the treatment of skin
      disease?
AB  - The practice of medicine transcends our neat borders of demarcation between the
      myriad of medical specialties and medical disciplines. There are no two
      specialties in which this clinical interface is more blurred than the clinical
      interface between allergy and dermatology. With a background in both dermatology
      and allergy, I address where the specialty of allergy/ immunology is heading, as
      we navigate the coastal waters separating my two primary disciplines. I also
      discuss the tools traditionally used only in dermatology, which are now being
      used increasing by a vanguard of allergists to aid in the diagnosis and treatment
      of allergic skin disease.

PMID- 15576897
TI  - Multi-colored simplified asthma guideline reminder: why pragmatic asthma tools
      are needed in real-world practice.
AB  - Asthma is a chronic disease that is highly prevalent around the world with
      increasing societal and economic burden. National Asthma Educational and
      Preventive Program (NAEPP) and Global Initiative for Asthma (GINA) are evidence
      based documents designed to help clinicians make appropriate decisions for their
      patients and to reduce undesirable variation in the care of asthmatic patients.
      It is a generally accepted fact that asthma specialists achieved better and
      improved asthma outcomes for their patients when compared with primary care
      physicians (PCPs). These outcome differences are somewhat related to PCPs' poor
      adherence to published NAEPP guidelines. Multi-Colored Simplified Asthma
      Guideline Reminder (MSAGR) is the first user-friendly single-sheet convenient
      asthma tool designed for clinicians after barriers to the poor adherence to
      asthma guidelines in primary care settings were identified. Voluntary acceptance
      and utilization of MSAGR resulted in fewer emergency room visits and
      hospitalizations for their patients. General acceptance of MSAGR (more than 1
      million copies requested by clinicians globally), and overwhelming positive
      comments by asthma care providers, strongly advocate a need for real-time,
      pragmatic clinical tools not only in asthma, but also in other chronic diseases
      such as chronic obstructive pulmonary disease, diabetes mellitus, hypertension,
      and depression, etc. In this brief review, we discuss how clinicians, patients,
      and payers are utilizing these simplified asthma tools to improve asthma care in
      their community.

PMID- 15576898
TI  - Fatalities following allergen immunotherapy.
AB  - Allergen immunotherapy has been in use for nearly 100 yr and has become an
      important method of reducing allergic symptoms in select patients with allergic
      rhinitis, asthma, and insect venom hypersensitivity. Unfortunately, immunotherapy
      has been associated with anaphylaxis and death. Although the relative risk of
      severe reactions to immunotherapy is low, the number of such reactions has
      increased since the introduction of standardized and more potent extracts. There
      are a number of risk factors associated with such severe anaphylactic reactions.
      Such risk factors include errors in dosage, failure to reduce the dosage after a
      longer than scheduled interval, administration of the wrong extract, inadvertent
      intravenous administration, failure to postpone injection because of infection or
      asthma exacerbation, failure to observe patients for appropriate length of time,
      failure to adhere to guidelines for established contraindications, concurrent use
      of beta-adrenergic blocking agents, uses of mixtures of allergens, immunotherapy
      during the active allergy season, and types of allergens. In this review, we
      focus on these and other risk factors in attempts to reduce the risk of
      anaphylaxis following allergen immunotherapy.

PMID- 15576899
TI  - Diagnosis and treatment of allergic rhinitis and sinusitis during pregnancy and
      lactation.
AB  - Upper airway congestive symptoms during pregnancy have been recognized since the
      late 19th century (1). Among randomly selected pregnancies, as many as 18-30% of
      patients will report substantial symptoms of rhinitis and sinusitis, and this
      figure may be higher among patients with pre-existing atopic disease (2-4).
      "Rhinitis of pregnancy" can take many forms. In another chapter in this review,
      Dr. Elergard discusses a form of rhinitis in pregnancy that occurs as a result of
      physiologic changes specific to pregnancy. This is to be distinguished from other
      forms of rhinitis coincident sometimes aggravated by pregnancy such as allergic
      rhinitis and sinusitis. The incidence of allergic conditions is 20-30% among
      women of childbearing years (5). Of those pregnant women with known allergies,
      some studies suggest that as many as 10-30% will experience increasing allergic
      symptoms during their pregnancy returning to their normal pre-pregnancy state
      after delivery (5-7). Postulated causes include those responsible for "rhinitis
      of pregnancy" such as increased circulating blood volume giving rise to nasal
      vascular engorgement and hormonal influences on nasal mucosal secretions and have
      been discussed in another chapter of this review (8,9).

PMID- 15576900
TI  - Cell migration: an overview.
AB  - Cell migration is an essential process for normal development and homeostasis
      that can also contribute to important pathologies. Not surprisingly, there is
      considerable interest in understanding migration on a molecular level, but this
      is a difficult task. However, technologies are rapidly emerging to address the
      major intellectual challenges associated with migration. In this chapter, we
      outline the basics of cell migration with an emphasis on the diverse systems,
      methodologies, and techniques described in this book. From the contributions
      presented, it is apparent that the next few years should produce major advances
      in our understanding of cell migration.

PMID- 15576901
TI  - Boyden chamber assay.
AB  - The Boyden chamber assay, originally introduced by Boyden for the analysis of
      leukocyte chemotaxis, is based on a chamber of two medium-filled compartments
      separated by a microporous membrane. In general, cells are placed in the upper
      compartment and are allowed to migrate through the pores of the membrane into the
      lower compartment, in which chemotactic agents are present. After an appropriate
      incubation time, the membrane between the two compartments is fixed and stained,
      and the number of cells that have migrated to the lower side of the membrane is
      determined. Therefore, the Boyden chamber-based cell migration assay has also
      been called filter membrane migration assay, trans-well migration assay, or
      chemotaxis assay. A number of different Boyden chamber devices are available
      commercially. The method described in this chapter is intended specifically for
      measuring the migration of Madin-Darby canine kidney cells using a 48-well
      chamber from Neuro Probe, Inc.

PMID- 15576902
TI  - Wound-healing assay.
AB  - The wound-healing assay is simple, inexpensive, and one of the earliest developed
      methods to study directional cell migration in vitro. This method mimics cell
      migration during wound healing in vivo. The basic steps involve creating a
      "wound" in a cell monolayer, capturing the images at the beginning and at regular
      intervals during cell migration to close the wound, and comparing the images to
      quantify the migration rate of the cells. It is particularly suitable for studies
      on the effects of cell-matrix and cell-cell interactions on cell migration. A
      variation of this method that tracks the migration of individual cells in the
      leading edge of the wound is also described in this chapter.

PMID- 15576903
TI  - Analysis of cell migration using the Dunn chemotaxis chamber and time-lapse
      microscopy.
AB  - The directed migration of cells (chemotaxis) occurs not only during wound healing
      and inflammatory responses but also during embryonic development. However, the
      intracellular signaling pathways that enable a cell to detect a chemoattractant
      and subsequently migrate toward the source are not clearly defined. The Dunn
      chemotaxis chamber in conjunction with time-lapse microscopy is a powerful tool
      that enables the user to observe directly the morphological response of cells to
      a chemoattractant in real time. Here, we describe using the Dunn chemotaxis
      chamber to study the response of murine bone marrow-derived macrophages to colony
      stimulating factor-1. This is a particularly useful protocol as it can be adapted
      to study bone marrow-derived macrophages isolated from genetically modified mice
      and thus study the requirement for a specific protein in cell migration and
      chemotaxis.

PMID- 15576904
TI  - Cell-adhesion assays.
AB  - One of the most important properties of cells that are derived from multicellular
      organisms is their ability to adhere to extracellular matrix proteins or other
      cells. Analysis of cell-extracellular matrix and/or cell-cell adhesion,
      therefore, is of important value to experimental biologists as well as clinical
      investigators. Over the past several decades, many different cell-adhesion assays
      have been developed. Based on the experimental conditions, most of the cell
      adhesion assays fall into two categories, namely static adhesion assays and flow
      adhesion assays. Static assays are widely used to assess the adhesion of many
      types of cells (e.g., epithelial cells and fibroblasts) to the extracellular
      matrix. The flow adhesion assays are more appropriate for analysis of blood cell
      (e.g., leukocyte) adhesion to endothelial cells, to each other, or extracellular
      matrix proteins. This chapter describes two basic protocols, one for analysis of
      cell adhesion under static conditions and the other for measurement of cell
      adhesion under shear stress. In addition, variations to the basic protocols and
      areas where special attention is required for successful application of these
      methods are discussed.

PMID- 15576905
TI  - Cell-spreading assays.
AB  - A method is provided to quantitate the extent of cell spreading as a function of
      the expression level of transfected recombinant proteins. This chapter contains
      protocols for 1) replating and staining transfected cells for immunofluorescence
      microscopy, 2) optimizing image acquisition so that fluorescence intensity can be
      measured independent of cell morphology, and 3) quantitating cell area and
      expression levels of recombinant proteins for individual transfected cells using
      ImagePro-Plus software. This method can be used to further our understanding of
      intracellular signals and protein interactions that regulate cell spreading.

PMID- 15576906
TI  - Cell-scatter assay.
AB  - Cell scattering is used to describe the dispersion of compact colonies of
      epithelial cells induced by certain soluble factors such as growth factors,
      cytokines, and phorbol esters. The dispersal of epithelial colonies is a dynamic
      process usually initiated by membrane ruffling and centrifugal spreading of cell
      colonies. Subsequently, some cells within the colony begin to detach from their
      neighboring cells and exhibit a shape resembling that of motile fibroblasts.
      These cells continue to migrate, finally leading to a "scatter" phenomenon.
      Because the scattering of epithelial colonies possesses characteristics of
      epithelial-mesenchymal transition, such as the loss of epithelial cell-cell
      junctions and the acquisition of a motile mesenchymal cell phenotype, the scatter
      assay has been used for studying epithelial-mesenchymal transition and for
      detecting factors able to induce migratory behavior of cells. The method
      described in this chapter is intended specifically for measuring the scatter
      response of Madin-Darby canine kidney cells to hepatocyte growth factor
      stimulation.

PMID- 15576907
TI  - Cell migration analyses within fibroblast-derived 3-D matrices.
AB  - Research in cell biology often is based in tissue culturing cells on artificial
      substrates, such as plastic or glass. These artificial conditions are prone to
      distorting findings by persuading cells to adjust to artificial flat rigid
      surfaces. In contrast, the natural substrate for most cells in living organisms
      is the extracellular matrix (ECM), which is three-dimensional, complex, and
      dynamic in its molecular composition, and variable in pliability. Here we show
      how to measure the rates and directionality of fibroblasts motility within
      physiologically relevant in vivo-like cell-derived three-dimensional matrices.

PMID- 15576908
TI  - Tumor cell invasion assays.
AB  - The ability of tumor cells to invade is one of the hallmarks of the metastatic
      phenotype. To elucidate the mechanisms by which tumor cells acquire an invasive
      phenotype, in vitro assays have been developed that mimic the in vivo process.
      The most commonly used in vitro invasion assay is a modified Boyden chamber assay
      using a basement membrane matrix preparation, Matrigel, as the matrix barrier and
      NIH-3T3 conditioned media as the chemoattractant. The results obtained using this
      assay show a strong correlation between the ability of tumor cells to invade in
      vitro and their invasive behavior in vivo, which validates this assay as a
      measure of invasive potential. The methods presented in this chapter outline how
      the Matrigel in vitro invasion assay is performed.

PMID- 15576909
TI  - Analysis of endothelial cell migration under flow.
AB  - The migration of endothelial cells (ECs) play an important role in embryonic
      vasculogenesis, angiogenesis, and post-angioplasty reendothelialization. ECs are
      constantly subjected to fluid shear stress (the tangential component of
      hemodynamic forces) from blood flow, but the effects of shear stress on EC
      migration have not been well characterized until recently. We have used an in
      vitro flow system to apply shear stress to EC cultures and used imaging and
      biochemical techniques to analyze EC migration under well-defined flow
      conditions. Time-lapse microscopy and cell tracing analysis generated
      quantitative information on EC migration under flow, and this assay was used to
      dissect the signaling events involved in shear stress-induced EC migration. By
      expressing green fluorescent protein-tagged molecules in EC, cell focal adhesions
      and cytoskeleton were visualized and quantified in living cells under flow, which
      provides temporal and spatial resolution for mechanotransduction at the molecular
      level. The studies on EC migration under flow will advance our understandings on
      vascular repair and remodeling in vivo, and provide a rational basis for the
      development of strategy to promote endothelialization and vascularization in
      tissue-engineered constructs.

PMID- 15576910
TI  - Angiogenesis assays in the chick CAM.
AB  - The growth of new blood vessels from pre-existing vascular elements, or
      angiogenesis, involves coordinated signals to the adhesion, migration, and
      survival machinery within the target endothelial cell. Agents that interfere with
      any of these processes may therefore influence angiogenesis. Here, we describe
      the angiogenesis assay in the chick chorioallantoic membrane (CAM). The CAM is a
      useful tool to studying angiogenesis because 1) it is amenable to both
      intravascular and topical administration of study agents, 2) it is a relatively
      rapid assay, and 3) it can be adapted very easily to study angiogenesis-dependent
      processes, such as tumor growth. Importantly, the CAM provides a physiological
      setting that permits investigation of pro- and anti-angiogenic agent interactions
      in vivo.

PMID- 15576911
TI  - Investigations of neuronal migration in the central nervous system.
AB  - The migration of neuronal precursor cells is essential for the formation of the
      embryonic nervous system and for the maintenance of the adult nervous system.
      Modern approaches have greatly facilitated molecular and cellular studies of
      mechanisms underlying neuronal migration. Here we use the cells migrating from
      the anterior subventricular zone to the olfactory bulb as a model to discuss in
      some detail how neuronal migration can be studied. These methods can be adapted
      to other models of neuronal (or somatic cell) migration.

PMID- 15576912
TI  - Analysis of Cell Migration in Caenorhabditis elegans.
AB  - This chapter is concerned with a method of analysis and quantification of cell
      migration defects in mutants of the nematode worm Caenorhabditis elegans. The
      method takes advantage of transgenic expression of the green fluorescent protein
      to visualize migrating cells. By following these protocols, one will be able to
      analyze cell migration defects in new mutant strains for comparison to wild-type
      and to other mutants. Techniques described include obtaining wild-type and mutant
      worm strains as well as strains harboring green fluorescent protein transgenes;
      maintenance and manipulation of C. elegans in the laboratory; introducing
      transgenes into different genetic backgrounds; mounting worms for fluorescence
      microscopy; and scoring and analysis of cell migration defects.

PMID- 15576913
TI  - Analysis of cell migration using Drosophila as a model system.
AB  - There are a number of reasons to use Drosophila as a model system to study cell
      migration. First and foremost is the availability of an arsenal of powerful
      genetic techniques that can be deployed, permitting the study of cell migration
      in vivo, in the context of the entire organism. This is especially important for
      the study of a complex behavior that can be dramatically affected by small
      changes in environmental conditions. Several different types of cell migrations
      occur during Drosophila development. In this chapter, we focus on cell migrations
      that have been subjected to the most intense scrutiny. We describe each of the
      cell types and their trajectories and provide information regarding markers that
      are useful for the study of each cell type and mutations that affect their
      migrations. In addition, we provide protocols for staining embryos and
      manipulating gene function in each of the migratory populations. Finally, we
      offer some advice concerning the analysis and interpretation of mutant
      phenotypes.

PMID- 15576914
TI  - Imaging cell movement during dorsal closure in Drosophila embryos.
AB  - During Drosophila embryogenesis, many cells and tissues undergo complex
      morphogenetic movements, such as ventral furrow formation, germ band extension
      and retraction, and dorsal closure. The best way to study and understand the cell
      behaviors during such tissue movements is to image them live using time course
      analysis. The Drosophila embryo lends itself perfectly to live imaging for
      several reasons: powerful genetics allow transgenic embryos expressing green
      fluorescent protein-fusion proteins to be quickly and easily generated and the
      expression domains of these reporters can be efficiently controlled using the
      GAL4-upstream activator sequence system. Embryos will survive for several hours
      mounted on a slide in a gas-permeable oil, such as Voltalef or Halocarbon, during
      which time they will undergo normal development and can be easily imaged using a
      confocal laser scanning microscope. Here, we describe in detail a protocol for
      live imaging of Drosophila embryos which, in our hands, is routinely used to
      study dorsal closure but is suitable for the live study of any process involving
      cell motility, be it a coordinated tissue movement such as dorsal closure or the
      movement of individual cells such as hemocytes within the embryo.

PMID- 15576915
TI  - Analysis of cell movements in zebrafish embryos: morphometrics and measuring
      movement of labeled cell populations in vivo.
AB  - Cell movements occur in all phases of animal life from embryogenesis, to
      maintaining adult organs, to comprising a critical component of pathology. During
      gastrulation, cells demonstrate a repertoire of morphogenetic movements
      coordinated with fate inductions to sculpt the embryonic body. The morphogenetic
      behaviors, underlying mechanisms, and their control, are the subject of much
      current study. External development of the transparent zebrafish embryo, the
      abundance of mutations influencing cell movements, as well as a range of
      observation and manipulation methods, make the zebrafish valuable for cell
      movement studies. This chapter offers a conceptual background for analysis of
      gastrulation cell movements by reviewing how region specific cell movements shape
      the wild-type zebrafish embryo, and how defective morphogenetic movements alone
      or in combination with altered cell fate specification distort the body plans of
      known zebrafish mutants. We furnish methods for the morphometric analysis of
      embryonic shape and organ rudiments in live and fixed embryos, and present data
      collected from live wild-type, dorsoventral patterning (somitabun and chordino)
      and convergence and extension (knypek and trilobite) classes of mutants. We
      provide a method for quantitative assessment of the movements of cell populations
      in vivo, and a method for determining whether cell fate and/or movement are
      disturbed.

PMID- 15576916
TI  - The Xenopus embryo as a model system for studies of cell migration.
AB  - In this chapter, we describe procedures for the microsurgical removal of cells
      and tissues from early-stage embryos of the amphibian Xenopus laevis. Using
      simple culture conditions and artificial substrates, these preparations undergo a
      variety of quantifiable cellular behaviors that closely mimic cell migration in
      vivo. Two general methods are described. The first includes procedures for
      obtaining a dorsal marginal zone explant from early gastrulae in order to
      investigate the sheet-like extension and migration of the mesendoderm that
      spreads to cover the inner surface of the blastocoel roof in intact embryos. This
      preparation allows high-resolution analyses of cellular and subcellular events in
      a contiguous tissue preparation. The second describes methods for the isolation
      of cranial neural crest cells from tailbud stage embryos. Cranial neural crest
      tissue cultured in vitro on fibronectin will undergo segmentation and migrate as
      streams of cells as they do in the developing head. Each of these robust
      preparations provides an excellent example of the migratory events that are
      possible to observe in vitro using amphibian embryos.

PMID- 15576917
TI  - Neural crest migration methods in the chicken embryo.
AB  - Neural crest cells emerge from the neural tube early in development. They migrate
      extensively throughout the embryo and form most of the head and peripheral
      nervous system, giving rise to sensory and sympathetic ganglia, heart regions,
      adrenal cells, head bones, teeth, muscle cells, sensory organs, melanocytes, and
      other cell types. The neural crest is interesting because of its unique origin,
      development and differentiation. These cells are initially part of the dorsal
      neural tube, with a clear epithelial character; later, they transform into
      actively motile mesenchymal cells. Little is known about the underlying mechanism
      directing this process. It remains unknown why neural crest cells target
      particular derivatives (neurons, heart muscle and glia) and body regions
      (peripheral nerves, heart, skin, head and gut). Neural crest migration can be
      divided into three stages: 1) emigration from the neural tube; 2) migration along
      defined pathways; and 3) cessation of migration. At the onset of migration,
      neural crest cells lose their epithelial nature within the neural tube and
      transform into a migratory, mesenchymal cell type. Neural crest development has
      been best studied in avian embryos, which are amenable to surgical manipulation,
      cell marking techniques, cell culture and transgenesis by electroporation and
      retrovirally mediate gene transfer. The methods outlined below are those
      typically used to study and understand the different factors and signals
      necessary for the neural crest development before and during their migration.

PMID- 15576918
TI  - In vivo and in vitro models of Mammalian angiogenesis.
AB  - Angiogenesis is a complex process involving the organization of proliferating
      endothelial cells into new blood vessels. Both in vivo models and in vitro models
      are important for investigating angiogenesis and for defining the involvement of
      specific molecules. This chapter describes a basic mouse model of vascular
      endothelial growth factor-driven angiogenesis in mouse skin together with a
      modified version of this model in which retrovirus-packaging cells are included
      as a means to efficiently achieve retroviral transduction in vivo. With this
      approach, the contributions of specific proteins to angiogenesis can be defined.
      In addition, we describe a model of capillary morphogenesis in vitro that uses
      microvascular endothelial cells transduced with retrovirus in culture. This in
      vitro model provides a complementary strategy for investigating the importance of
      specific molecules for angiogenesis.

PMID- 15576919
TI  - Measurement of protein tyrosine phosphorylation in cell adhesion.
AB  - This chapter describes biochemical, immunochemical, and microscopic approaches to
      measure protein tyrosine phosphorylation after cell adhesion. We have outlined
      detailed procedures to biochemically examine the phosphotyrosine content of
      cellular proteins by Western blotting, which in some cases can be performed using
      phospho-specific antibodies. Furthermore, we have described in detail the
      examination of subcellular localization of phosphotyrosine-containing proteins in
      focal adhesions using immunofluorescence. Finally, a quantitative fluorescence
      microscopic technique using an SH2-containing phosphotyrosine reporter to monitor
      tyrosine phosphorylation in focal adhesions in live cells is described.

PMID- 15576920
TI  - Cell-adhesion assays: fabrication of an E-cadherin substratum and isolation of
      lateral and Basal membrane patches.
AB  - Cell adhesion between cells and with the extracellular matrix (ECM) results in
      dramatic changes in cell organization and, in particular, the cytoskeleton and
      plasma membrane domains involved in adhesion. However, current methods to analyze
      these changes are limited because of the small areas of membrane involved in
      adhesion, compared to the areas of membrane not adhering (a signal to noise
      problem), and the difficulty in accessing native protein complexes directly for
      imaging or reconstitution with purified proteins. The methods described here
      overcome these problems. Using a mammalian expression system, a chimeric protein
      comprising the extracellular domain of E-cadherin fused at its C-terminus to the
      Fc domain of human IgG1 (E-cadherin:Fc) is expressed and purified. A chemical
      bridge of biotin-NeutrAvidin-biotinylated Protein G bound to a silanized glass
      cover slip is fabricated to which the E-cadherin:Fc chimera binds in the correct
      orientation for adhesion by cells. After cell attachment, the basal membrane (a
      contact formed between cellular E-cadherin and the E-cadherin:Fc substratum) is
      isolated by sonication; a similar method is described to isolate basal membranes
      of cells attached to ECM. These membrane patches provide direct access to protein
      complexes formed on the membrane following cell-cell or cell-ECM adhesion.

PMID- 15576921
TI  - Application of microscope-based FRET to study molecular interactions in focal
      adhesions of live cells.
AB  - This chapter describes the use of microscope-based fluorescence resonance energy
      transfer to follow dynamic interaction of molecules localized at focal adhesions.
      We first outline the significance of studying dynamic interactions in focal
      adhesions of living cells, and second provide an overview of the method itself.
      This is followed by a protocol for fluorescence resonance energy transfer
      measurements in live cells.

PMID- 15576922
TI  - Use of multiphoton imaging for studying cell migration in the mouse.
AB  - We describe a method for studying cell motility in the living mouse using
      multiphoton microscopy. The procedure consists of mouse anesthesia, labeling of
      target cells with enhanced green fluorescent protein by infection with
      recombinant adenovirus, implantation of beads carrying chemoattractant,
      preparation of the mouse for imaging, and imaging of individual cell motions via
      multiphoton microscopy. Two-photon fluorescence excitation of enhanced green
      fluorescent protein allows visualization of cells within the dermis, whereas
      second harmonic generation (a non-linear scattering process) allows a
      simultaneous detailed definition of the dermis structure.

PMID- 15576923
TI  - Using microfluidic channel networks to generate gradients for studying cell
      migration.
AB  - In this chapter, we will discuss a method for the generation of gradients that
      can be quantitatively used for studying directional cell migration. Microfluidic
      networks, which serially split and remix small volumes of solutions under laminar
      flow conditions to generate a series of microchannels of increasing protein
      concentration. At a juncture of these microchannels, where a single broad channel
      is formed, a protein concentration gradient can be easily achieved. This method
      is highly useful because of the ability with which we can control, manipulate and
      analyze chemical gradients and cells' chemotactic behavior in a quantitative
      manner.

PMID- 15576924
TI  - Cell cycle molecules and mechanisms of the budding and fission yeasts.
AB  - The cell cycles of the budding yeast Saccharomyces cerevisiae and the fission
      yeast, Schizosaccharomyces pombe are currently the best understood of all
      eukaryotes. Studies in these two evolutionarily divergent organisms have
      identified common control mechanisms, which have provided paradigms for our
      understanding of the eukaryotic cell cycle. This chapter provides an overview of
      our current knowledge of the molecules and mechanisms that regulate the mitotic
      cell cycle in these two yeasts.

PMID- 15576925
TI  - The plant cell cycle: an overview.
AB  - This chapter reviews the basic features of plant cell proliferation. Although
      plant cell division seems to be largely similar to animals and fungi, there are a
      number of peculiarities that are perhaps related to their lifestyle and
      development. Initial comparisons of animal, fungal, and plant genomes suggest
      that the central cell division and growth machinery are largely similar but that
      some key regulatory molecules found in animals appear to be missing from plants.
      Also, many of the intracellular signaling molecules that coordinate growth during
      development and the proteins involved in their perception seem to be different
      between the groups. In some cases, this reflects true divergence in the
      underlying mechanism, but high rates of gene sequence divergence could explain
      other examples. However, what is undisputable is that plant and animal cells are
      highly adapted to different niches and that this is reflected in quite different
      behavior.

PMID- 15576926
TI  - The C. elegans cell cycle: overview of molecules and mechanisms.
AB  - The nematode C. elegans provides an animal model that allows for genetic
      dissection of cell cycle regulation in the context of development. Processes such
      as progression through meiotic prophase, spindle function, chromosome
      segregation, and cytokinesis are attractive topics to study in the worm, because
      of their relative visibility and susceptibility to RNA interference. In addition,
      the reproducible cell lineage greatly helps the identification and
      characterization of mutants that affect cell cycle entry or exit during larval
      development. This chapter looks at cell division as an integral part of C.
      elegans development, describes how it can be studied in the worm and summarizes
      some of the conserved cell cycle components described to date.

PMID- 15576927
TI  - Developmental control of growth and cell cycle progression in Drosophila.
AB  - Drosophila melanogaster provides an outstanding experimental system to study the
      regulation of cell cycle progression during animal development. Sophisticated
      forward and reverse genetic techniques and the ability to observe detailed cell
      biological phenomena in vivo have allowed an unparalleled analysis of the cell
      cycle in the context of a whole animal. This chapter provides an overview of the
      diverse modes of cell cycle control that are utilized at different stages of
      Drosophila development.

PMID- 15576928
TI  - The Xenopus cell cycle: an overview.
AB  - Oocytes, eggs, and embryos from the frog Xenopus laevis have been an important
      model system for studying cell cycle regulation for several decades. First,
      progression through meiosis in the oocyte has been extensively investigated.
      Oocyte maturation has been shown to involve complex networks of signal
      transduction pathways, culminating in the cyclic activation and inactivation of
      maturation promoting factor (MPF), which is composed of cyclin B and cdc2. After
      fertilization, the early embryo undergoes rapid simplified cell cycles, which
      have been recapitulated in cell-free extracts of Xenopus eggs. Experimental
      manipulation of these extracts has given a wealth of biochemical information
      about the cell cycle, particularly concerning DNA replication and mitosis.
      Finally, cells of older embryos adopt a more somatic-type cell cycle and have
      been used to study the balance between cell cycle and differentiation during
      development.

PMID- 15576929
TI  - The mammalian cell cycle: an overview.
AB  - In recent years, we have witnessed major advances in our understanding of the
      mammalian cell cycle and how it is regulated. Normal mammalian cellular
      proliferation is tightly regulated at each phase of the cell cycle by the
      activation and deactivation of a series of proteins that constitute the cell
      cycle machinery. This review article describes the various phases of the
      mammalian cell cycle and focuses on the cell cycle regulatory molecules that act
      at each stage to ensure normal cellular progression.

PMID- 15576930
TI  - Synchronization of cell populations in G1/S and G2/M phases of the cell cycle.
AB  - The method described in the following chapter utilizes a double thymidine block
      (an inhibitor of DNA synthesis) followed by treatment of cells with nocodazole (a
      mitotic inhibitor) to obtain large cell populations at distinct phases of the
      cell cycle. Treatment with double thymidine results in a G1/S-phase arrested cell
      population, and the use of flow cytometry allows progression of the cells through
      the cell cycle to be monitored. Flow cytometry enables the calculation of timings
      for collection of cells at distinct cell cycle phases from G1/S (following
      treatment with thymidine) through to G2/M (owing to the presence of nocodazole).

PMID- 15576931
TI  - Mapping origins of DNA replication in eukaryotes.
AB  - Methods are described here to map an origin of replication in eukaryotes.
      Replicating DNA is enriched by BND cellulose column chromatography and by lambda
      exonuclease digestion; this approach has largely superceded enrichment by BrdU
      incorporation. The general area in which replication begins can be deciphered by
      neutral/neutral 2D gel electrophoresis: a restriction fragment containing the
      replication bubble will form a bubble arc on these gels. A more sensitive method
      employs PCR analysis of nascent strands that are size-fractionated. Once the
      general area containing the origin of bidirectional replication has been mapped,
      a finer level of resolution can be obtained by replication initiation point (RIP)
      mapping, in which start sites of DNA synthesis are identified at the nucleotide
      level.

PMID- 15576932
TI  - In situ assay for analyzing the chromatin binding of proteins in fission yeast.
AB  - An in situ technique for studying the chromatin binding of proteins in single
      fission yeast cells (Schizosaccharomyces pombe) is described. Cells are
      permeabilized by enzymatic digestion and extracted with a detergent-containing
      buffer. This procedure removes soluble proteins, but proteins that are bound to
      insoluble cell structures such as chromatin are retained, and overall cell
      morphology is maintained. Extraction of proteins is monitored by fluorescence
      microscopy, either using fluorescently tagged proteins or by indirect
      immunofluorescence. This method allows the chromatin association of proteins to
      be correlated with other cell cycle events without the need for cell
      synchronization.

PMID- 15576933
TI  - Application of magnetic beads to purify cells transiently transfected with
      plasmids encoding short hairpin RNAs.
AB  - Short interfering (si) RNAs are commonly used to knock down expression of
      proteins in mammalian cells and thereby investigate protein function. siRNAs were
      originally introduced into mammalian cells by transient transfection of short,
      synthetic, double-stranded RNA oligonucleotides. More recently, a convenient,
      more cost-effective approach has been developed that makes use of plasmids
      encoding short hairpin (sh) RNAs, which are transiently or stably transfected
      into cells. After expression in cells, shRNAs are processed by the cell to the
      corresponding siRNAs. However, most protocols for transient transfection of
      plasmid DNAs introduce the DNA into a minority of the total cells. Therefore, to
      investigate the biochemical effects of protein knockdown, it is necessary to
      purify the transfected cells. This can be done by cotransfection of a plasmid
      encoding the cell surface marker protein, CD19 or CD20, followed by
      immunopurification of the CD19- or CD20-expressing cells with magnetic beads. The
      purified cells can then be used for a wide range of biochemical analyses. In
      addition, since the CD19/CD20 cell surface marker approach can be readily
      combined with analysis of cell cycle distribution of propidium iodide-stained
      cells, it is straightforward to determine simultaneously the biochemical and cell
      cycle effects of a knocked-down protein.

PMID- 15576934
TI  - The cell cycle and virus infection.
AB  - A number of different viruses interact with the cell cycle in order to subvert
      host-cell function and increase the efficiency of virus replication; examples can
      be found from DNA, retro, and RNA viruses. The majority of studies have been
      conducted on DNA and retroviruses whose primary site of replication is the
      nucleus, but increasingly a number of researchers are demonstrating that RNA
      viruses, whose primary site of replication is normally the cytoplasm, also
      interfere with the cell cycle. Viral interference with the cell cycle can have a
      myriad of different effects to improve virus infection, for example to promote
      replication of viral DNA genomes, or to delay the cell cycle to allow sufficient
      time for RNA virus assembly. Although cell cycle control is fairly well
      characterized in terms of checkpoints and control molecules (e.g., cyclins), in
      recent years several researchers have demonstrated that the nucleolus is also
      involved in cell cycle control. The nucleolus and associated subnuclear
      structures can sequester cell cycle regulatory complexes, and nucleolar proteins
      also have a direct and indirect effect on the cycling cell. Viruses also interact
      with the nucleolus. In order to study the interactions between a virus and the
      cell cycle and vice versa we have developed and adapted a number of different
      approaches and strategies. These include determinations of virus yield and
      measurements of virus replication to flow cytometry and confocal analysis of the
      host cell. Increasingly we have found that proteomic approaches allow the rapid
      analysis of a whole plethora of cell cycle proteins that may be affected by virus
      infection.

PMID- 15576935
TI  - Methods for preparation of proteins and protein complexes that regulate the
      eukaryotic cell cycle for structural studies.
AB  - The determination of structures for proteins that control the eukaryotic cell
      cycle by nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography
      has made a significant contribution to our understanding of the molecular
      mechanisms that control cell cycle progression. CDK2 has proved particularly
      tractable to structural analysis, and CDK2 in complex with various regulatory
      proteins and in different phosphorylation states provides a paradigm for the
      control of this important kinase family. This chapter describes a number of
      protocols that can be used to prepare CDKs and selected CDK binding proteins
      suitable for structural studies by heterologous expression in either E. coli or
      insect cells.

PMID- 15576936
TI  - E2F transcription factors and pRb pocket proteins in cell cycle progression.
AB  - The E2F-family of transcripion factors exerts fascinating and contrasting
      functions in transcriptional repression and activation of genes regulating
      proliferation, apoptosis, and differentiation. E2F is principally regulated by
      its temporal association with retinoblastoma pocket protein (pRb) family members.
      In turn, pRb is regulated through phosphorylation by cyclin-dependent kinase
      (cdk). The activity of cdk is negatively regulated by cdk-inhibitors, exemplified
      by p16INK4a, p21CIP1, and p27KIP1. Therefore, positive and negative signaling
      events converge on E2F activity resulting in distinct growth-controling and
      apoptotic activities. Here we describe the immunocytochemical detection of E2F,
      genomic DNA, BrdU-incorporation, and mitosis in cardiomyoctes. A detailed
      protocol is given to illustrate this technique in primary heart muscle cells.

PMID- 15576937
TI  - Forkhead (FOX) transcription factors and the cell cycle: measurement of DNA
      binding by FoxO and FoxM transcription factors.
AB  - Certain forkhead (FOX) transcription factors have been shown to play an intrinsic
      role in controlling cell cycle progression. In particular, the FoxO subclass has
      been shown to regulate cell cycle entry and exit, whereas the expression and
      activity of FoxM1 is important for the correct coupling of DNA synthesis to
      mitosis. In this chapter, I describe a method for measuring FoxO and FoxM1
      transcription factor DNA binding in nuclear extracts from mammalian cells.

PMID- 15576938
TI  - Measurement of geminin activity in Xenopus egg extracts.
AB  - Geminin is an unstable protein that inhibits DNA replication by interfering with
      the assembly of prereplication complex at replication origins. Geminin is thought
      to prevent a second round of replication during late S- or G2-phase. The protein
      is destroyed by ubiquitin-dependent proteolysis during mitosis, allowing a new
      round of replication in the next cell cycle. This chapter describes protocols for
      measuring the stability of geminin and two of its activities, the inhibition of
      replication and the inhibition of pre-RC loading.

PMID- 15576939
TI  - CDK-activating kinases: detection and activity measurements.
AB  - All cyclin-dependent kinases (CDKs) involved in eukaryotic cell cycle control
      require phosphorylation at a conserved threonine (or serine) residue within the
      activation- or T-loop to attain full enzymatic activity. The enzyme responsible
      for this activating phosphorylation, the CDK-activating kinase (CAK), is
      therefore essential for proliferation of all eukaryotic cells. We describe
      methods to assess the T-loop phosphorylation state of the major mammalian CDKs in
      vivo; to measure the levels of CAK activity in cell-free extracts; and to analyze
      the abundance, subunit composition, and phosphorylation state of CAK complexes in
      metazoan cells. When derangement of normal CDK regulation is suspected as a cause
      of disturbed cell cycle progression, the combination of these methodologies can
      ascertain whether a primary CAK defect is the explanation.

PMID- 15576940
TI  - Cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors:
      detection methods and activity measurements.
AB  - The cyclin/cyclin-dependent kinase (Cdk) complexes and the Cdk inhibitors (CDKI)
      are crucial regulators of cell cycle progression in all eukaryotic cells. Using
      rat cardiac myocytes as a model system, this chapter provides a detailed account
      of methods that can be employed to measure both cyclin/Cdk activity in cells and
      the extent of CDKI inhibitory activity present in a particular cell type.

PMID- 15576941
TI  - Measurement of Wee kinase activity.
AB  - The Wee kinases (Wee1, Wee2, and Myt1) are major regulators of mitotic entry.
      They function by phosphorylating Cdc2 and related Cdks on conserved tyrosine and
      threonine residues. This phosphorylation blocks the activity of the Cdc2 and
      prevents entry into mitosis. The abundance and activity of the Wee kinases are
      regulated during the cell cycle and development. In this chapter, we describe
      several procedures to measure the activity of the Wee kinases found either in
      crude extracts or in purified preparations. Specific protocols include the
      production and purification of recombinant Cdc2/Cyclin B substrate, the
      production of crude subcellular extract fractions, the purification of endogenous
      or recombinant Wee kinases, Wee kinase assays, and the Histone H1 kinase assay to
      measure Cdc2 activity. In addition, support protocols are provided that describe
      the use and production of Ni-IDA beads for the purification of Histidine-tagged
      proteins, and the use of the baculovirus expression system to produce recombinant
      proteins.

PMID- 15576942
TI  - CDC25 dual-specificity protein phosphatases: detection and activity measurements.
AB  - Most cyclin-dependent kinases are negatively regulated by phosphorylation of two
      residues, a threonine at residue 14 and a tyrosine at residue 15. These residues
      are dephosphorylated by the cdc25 family of dual-specificity phosphatases leading
      to cell cycle progression. These phosphatases are inactivated by cellular
      checkpoint pathways in response to DNA damage leading to cell cycle arrest.
      Checkpoint pathways regulate the function of these phosphatases by regulating
      their stability, localization, association with substrate, and their activity.
      Hence, determining these properties for the cdc25 family of phosphatases becomes
      crucial for understanding how checkpoint pathways regulate the function of the
      cdc25 family members and, hence, cell cycle progression. This chapter describes
      methods to determine the activity, levels, phosphorylation status, and
      localization of both endogenous and overexpressed cdc25 proteins.

PMID- 15576943
TI  - Assaying cell cycle checkpoints: activity of the protein kinase Chk1.
AB  - Eukaryotic cells regulate progression through the cell cycle in response to DNA
      damage. Cell cycle checkpoints are the signal transduction pathways that couple
      the detection of DNA damage to the proteins that control transitions in the cell
      cycle. The protein kinase Chk1, originally discovered in fission yeast, but
      conserved in humans, is essential for preventing mitotic entry in the presence of
      DNA damage or blocks to DNA replication that cannot be reconciled. Chk1 is
      phosphorylated in response to DNA damage. Phosphorylation depends on the activity
      of conserved components of the checkpoint pathway including Rad3, a member of the
      ATM/ATR family of kinases. Phosphorylation leads to activation of Chk1 kinase
      activity. In this chapter, we describe an assay for monitoring the activity of
      Chk1 isolated.

PMID- 15576944
TI  - Polo-like kinase-1: activity measurement and RNAi-mediated knockdown.
AB  - Polo-like kinase-1 (Plk-1) is an important cell cycle regulatory kinase that has
      been implicated in a multitude of cell cycle events. In this chapter we review
      those multiple functions of Plk-1 and describe the methods routinely used in our
      laboratory to purify Plk-1 from cellular lysates and measure Plk-1 kinase
      activity in vitro. In addition, we describe a method to analyze cell cycle
      progression after depletion of Plk-1 by RNA-interference in tissue culture cells.

PMID- 15576945
TI  - The Ipl1/Aurora kinase family: methods of inhibition and functional analysis in
      mammalian cells.
AB  - The Ipl1/Aurora family of protein kinases are required for accurate chromosome
      segregation. Because members of this family are often overexpressed in human
      tumors, they have recently received much attention, both from the academic
      community and the pharmaceutical industry. Indeed, two small molecule Aurora
      kinase inhibitors have recently been described. In this chapter, we describe
      several methods for investigating the function of the Aurora kinases, focusing on
      Aurora B. We describe the use of the small-molecule inhibitor ZM447439, RNA
      interference, and overexpression of a catalytic mutant. All of these methods have
      proved useful in studying Aurora B as well as validating it as a potential
      anticancer drug target. However, while all three methods are useful for probing
      the function of Aurora B, each has inherent advantages and disadvantages.
      Furthermore, because the mechanism underlying the inhibition is different in each
      case, caution must be taken when interpreting the data.

PMID- 15576946
TI  - Purification of the Ndc80 kinetochore subcomplex from Xenopus eggs.
AB  - The identification of protein binding partners often facilitates understanding of
      protein complex function. However, identifying binding partners has proven
      difficult because proteins are often bound to insoluble structures or are only
      present during certain stages of the cell cycle. Fortunately, Xenopus eggs
      stockpile many proteins, which are typically insoluble, as soluble subcomplexes
      to facilitate rapid early embryonic divisions. We exploited this by developing a
      purification scheme using Xenopus egg extracts to isolate Coomassie-stainable
      amounts of the xNdc80 kinetochore complex. In this scheme Xenopus eggs are
      directly made into a mitotic high-speed supernatant and then flowed over three
      chromatographic columns: heparin, Mono-Q, and Superose 6 gel filtration columns.
      A final immunoprecipitation is then performed from the peak Superose 6 column to
      yield Ndc80 complex purified to homogeneity. With minor modification and
      manipulation of Xenopus egg extracts, this protocol can easily be adapted for
      purification of other protein complexes.

PMID- 15576947
TI  - [Vascular injury and mortality in renal osteodystrophy].
AB  - Cardiovascular disturbance occupied 43.7% on causes of death in dialysis
      patients. It was confirmed that their deaths were, at least partially, caused by
      accelerated vascular damage which originates from renal osteodystrophy. This
      review describes calciphylaxis with very poor prognosis, and advanced
      calcification in blood vessels and soft tissues in dialysis patients. The
      relation of coronary artery calcification, of which the quantitative evaluation
      recently became possible by ultra-first CT, is outlined with special concern to
      their effects on the mortality.

PMID- 15576948
TI  - [Low PTH level and adynamic bone disease in dialysis patients].
AB  - Greater level of parathyroid hormone (PTH) than healthy subject is required to
      maintain appropriate bone turnover in dialysis patients. The skeletal resistance
      to PTH is the most important genesis of this phenomenon and the mechanism has
      been elucidated by the recent molecular biological techniques. Insufficient level
      of PTH induces not only adynamic bone disease but also cardiovascular diseases by
      ectopic calcification in soft tissues. Cardiovascular calcification is an
      important risk factor for the prognosis of dialysis patients, so the development
      of new therapeutic tools, that can adequately control PTH levels without
      hypercalcemia and hyperphosphatemia, are expected.

PMID- 15576949
TI  - [Risk factors of atherosclerosis in end-stage renal disease patients].
AB  - Patients with end-stage renal disease have greatly elevated risks of
      atherosclerotic disease. Vascular calcification in advanced atherosclerosis is a
      common feature in ESRD patients. Risk factors of atherosclerosis in ESRD patients
      are coronary risk factors such as hypertension, diabetes and hyperlipidemia and
      hyperphosphatemia. Bone associated proteins including osteopontin, matrix Gla
      protein and osteoprotegerin may be involved in the progression of
      atherosclerosis.

PMID- 15576950
TI  - [Extraskeletal actions of parathyroid hormone in hemodialysis patients].
AB  - In uremic patients, secondary hyperparathyroidism is caused by disturbances of
      calcium and phosphorus metabolism such as elevated plasma phosphate and reduced
      production of active vitamin D metabolites. Although the etiologies for
      complications in renal failure are multiple, there is evidence suggesting that
      increased circulating parathyroid hormone associated with secondary
      hyperparathyroidism may play important roles in uremic syndrome.

PMID- 15576951
TI  - [The present state of vitamin D supplementation or treatment among chronic
      dialysis patients].
AB  - Because the chronic renal failure state basically means the active vitamin D
      deficiency, the minimum physiological daily dose of active vitamin D should be
      supplemented in all of the patients. But few informations about the frequency of
      vitamin D supplementation or treatment are available in European countries and in
      the USA. Only the Japanese Society for Dialysis Therapy presented the frequency
      of it in 2002, which was about 40 % of the dialysis patients, unexpectedly as
      same as that in Shinraku-En Hospital in 1985. Hypercalcemia, uncontrollable
      hyperphosphatemia, low ALP, and low PTH might impair the vitamin D introduction.

PMID- 15576952
TI  - [Target range of PTH in uremia].
AB  - Skeletal resistance to parathyroid hormone (PTH) is well defined in patients with
      chronic renal failure. Recently, with the increased frequency of development of
      adynamic bone disease (ABD), it has been suggested that higher PTH is needed to
      maintain bone turnover in uremia. It has very recently been argued that the
      optimal PTH level for maintenance of skeletal bone remodeling may be insufficient
      to prevent the extraskeletal complications of cardiovascular systems.
      Furthermore, conventional intact PTH assay detects (7-84) PTH in addition to (1
      84) PTH and overestimate the actual activity of circulating PTH molecules in
      uremic patients. Thus, target range of PTH in uremic patients should be set by
      careful considerations.

PMID- 15576953
TI  - [The effects on bone of environmental cadmium exposure--summary of recent
      epidemiological studies].
AB  - In Itai-itai disease, which is the most severe manifestation of environmental
      cadmium exposure, the bone features are characteristic of osteomalacia induced by
      renal tubular dysfunction and osteoporosis. Lower bone mass and higher bone
      turnover have been observed in inhabitants of cadmium-exposed areas, compared
      with people in nonexposed areas in Japan. Decreased bone mass and increased bone
      fracture have been reported recently in large-scale epidemiological studies,
      conducted in Belgium and Sweden. An association between higher urinary cadmium
      and lower bone mass was also found in female Japanese. These studies suggest that
      environmental cadmium exposure could be a risk factor of osteoporosis even in the
      general population in Japan. The effect on bone could be caused indirectly
      through renal damage induced by cadmium exposure, or directly via an effect of
      cadmium on bone itself.

PMID- 15576954
TI  - [New interventions controlling parathyroid hormone].
AB  - Percutaneous direct injection of ethanol, calcitriol and the analogues to
      parathyroid glands under ultrasonography have been performed as a therapeutic
      option for advanced secondary hyperparathyroidism in uremic patients. The aim of
      these therapy is mass reduction of enlarged parathyroid glands and injection of
      maxacalcitriol may induce apoptosis of parathyroid cells. The indications and
      limitations of these therapy have been confirmed. However the most successful
      treatment for renal hyperparathyroidism is parathyroidectomy.

PMID- 15576955
TI  - [The optimum amount of vitamin D for osteoporosis: in case of activated vitamin D
      treatment].
AB  - Since the resistance factors for the effect of vitamin D increases by aging,
      ingestion of various nutrition factors, such as calcium, and vitamin D is
      important for prevention and medical treatment of osteoporosis. 1 alpha 25
      dihydroxyvitamin D(3) known as active form of vitamin D can stimulate calcium
      absorption from intestine and also it is used for the medical treatment of
      osteoporosis. The vitamin D action for the regulation of bone and mineral
      metabolism changes with the sufficiency states or the amounts of ingestion of
      vitamin D. Therefore, the action as a medicine is not simple. This article
      reviews the effect and its optimum ingestion amount of activated vitamin D in
      osteoporosis medical treatment.

PMID- 15576956
TI  - [Selection of the supplement in calcium intake].
AB  - Adequate calcium intake is one of the most important issues in the prevention and
      treatment of osteoporosis, which is considered a lifestyle-related disease.
      However, calcium is a nutrient that is rather difficult to take in appropriate
      amounts in traditional Japanese eating habits. Therefore, one of the effective
      means of preventing and treating osteoporosis is to supplement calcium intake,
      when an insufficient quantity is obtained in the three, daily meals. In addition
      to increasing the tolerable upper intake levels (UL) of calcium to 2,500 mg/day,
      and an instruction program for learning how to evaluate the nutritional state,
      and the right method of utilizing supplements is needed. Furthermore, learning
      how to balance other nutrients, such as mineral balance, should also be included.

PMID- 15576957
TI  - Vertebroplasty and kyphoplasty in the fractured osteoporotic spine.
AB  - Percutaneous vertebroplasty and kyphoplasty have during the last decade gained an
      increasing popularity in the treatment of osteoporotic fractures of the spine.
      The techniques, clinical results and complications are described. There is
      however a disturbing lack of scientific evidence regarding the efficacy of the
      procedures, no controlled studies are published. An ongoing prospective
      randomised study is presented.

PMID- 15576958
TI  - [Recent topics on bone remodeling].
AB  - The Wnt signaling pathway has recently been demonstrated to play an important
      role in regulation of bone formation. LRP5 is thought to signal through the
      canonical Wnt pathway. In humans, LRP5 loss-of-function mutations lead to low
      bone mass with fractures, while LRP5 gain-of-function mutations lead to high bone
      mass, thus identifying LRP5 as an important regulator of bone mass. Patients with
      sclerosteosis have a severe skeletal disorder with progressive bone overgrowth
      due to a loss of function of the SOST gene, which implicates its role as a
      suppressor of bone formation. Recent study revealed that SOST is a BMP antagonist
      with unique ligand specificity, negatively regulating bone formation by
      repressing BMP-induced osteoblast differentiation or function or both.

PMID- 15576959
TI  - [Osteoporosis from the point of view of dental practice].
AB  - When dentists examine a patient with osteoporosis, they should consider the
      condition of periodontal disease, because both osteoporosis and periodontal
      disease share the same symptoms such as reduction of the bone volume. Many
      studies have attempted to define the relationship between these two diseases.
      Although most studies support a positive association between them, the mechanism
      of correlation still remains unclear. To establish novel treatment modalities of
      these diseases, further studies are necessary to elucidate the detailed
      mechanisms of interaction between them.

PMID- 15576960
TI  - [The relationship between osteoporosis and oral diseases].
AB  - Few studies have been defined on the relationship between osteoporosis and oral
      diseases. The correlation among osteoporosis, periodontal diseases and dental
      loss is now well investigated. These investigations will lead to the elucidation
      of the osteoporotic bone diseases in the oral region. In this manuscript, the
      cases of oral diseases in elderly patients are shown.

PMID- 15576961
TI  - [Calcium and vitamin D intakes during infancy, childhood and adolescence].
AB  - Adequate intakes of calcium and vitamin D are necessary to prevent vitamin D
      deficiency or increase of plasma parathyroid hormone (PTH) level caused by
      vitamin D insufficiency. According to the National Nutrition Survey in Japan,
      2001 by Ministry of Health, Labour and Welfare, Japan, the average of calcium and
      vitamin D intakes have not met their RDA at 1-2 ages, and a low calcium intake
      was observed during adolescence. It is important to know the adequate intake of
      vitamin D to compensate the low calcium intake in Japanese children.

PMID- 15576962
TI  - [Calcium and vitamin D intake in premenopausal status].
AB  - Calcium and vitamin D do an important role in bone metabolism during pregnancy
      and lactation. It is said that calcium supplementation might have only a
      transient effect on postpartum bone mineral density. However, as for the Japanese
      women, calcium intake is insufficient. So pregnant and lactating women should
      supply calcium in particular for prevention of preeclampsia and osteoporosis.

PMID- 15576963
TI  - [Calcium and vitamin D intake after menopause].
AB  - It is thought that the decrease in bone mass after menopause is attributable to
      the changes with increasing age physiologically caused by rapid decrease in
      female hormone, decline in calcium absorption, and acceleration of bone
      resorption. But it is possible to prevent it from occurring by improving the
      living habits including daily dietary intake and physical exercise. In the 6th
      Revised Nutrient Intake Requirements for the Japanese People that was drawn up in
      1999, the intake criteria for vitamin D were also newly established. In the
      process of considering the prevention of osteoporosis in the future, the intake
      amounts of calcium and vitamin D will become extremely important contributing
      factors.

PMID- 15576964
TI  - [Alzheimer disease and calcium].
AB  - Calcium deficiency due to insufficient nutritional intake, poor intestinal
      absorption or excessive urinary loss leading to secondary hyperparathyroidism,
      increase of calcium influx into nerve cells causing cell death may lead to
      neuronal dysfunction and cell death as in dialysis encephalopathy with EEG
      changes and decrease of nerve conduction velocity in chronic renal failure and
      Alzheimer's disease in aging. Intracellular free calcium (Ca i) is increased in
      nerve cells showing neurofibrillar tangles associated with tau protein in
      Alzheimer's disease. Increase of Ca i facilitates presenilin mutation with
      consequent augmentation of short chain amyloid beta production which further
      increase Ca i. Peroxide radical production by amyloid beta and metals such as Fe,
      Cu and Mn is prompted by an increase of Ca i. Plasma membrane damage caused by
      lipid peroxidation further increases Ca i. Neurotoxic action of apolipoprotein
      E(4) increasing the risk for Alzheimer's disease may be explained by lipid
      peroxidation and rise of Ca i. Beneficial effect of estrogen in preventing
      Alzheimer's disease may also be explained by its anti-oxidant effect and
      stimulation of intestinal calcium absorption. By increasing calcium intake and
      administration of active form of vitamin D which cannot be sufficiently supplied
      by the aging kidney, one step forward should be made in the prevention and
      treatment of Alzheimer's disease.

PMID- 15576965
TI  - [Activity of the central nervous system and calcium].
AB  - The calcium influx plays an important role of the neuronal signal transduction of
      the central nervous system. There are several pathways of the calcium influx,
      such as voltage dependent calcium channel and receptor associated calcium
      channel. It has been demonstrated that these channels are associated with not
      only neurons but also glial cells. These channels are also indicated to be
      related to the neuronal plasticity of the hippocampus and cerebellum. Recently,
      the transcription factor CREB are also reported as the new mechanism of memory in
      hippocampus.

PMID- 15576966
TI  - [Calcium and the degenerative neurological diseases].
AB  - A condition of unbalanced minerals was found in soil and drinking water from
      three amyotrophic lateral sclerosis (ALS) foci on Guam, in the Kii Peninsula and
      in West New Guinea with a low concentration of calcium and magnesium coupled with
      a high concentration of aluminum and manganese. The current epidemiological
      studies in the Western Pacific including the Kii Peninsula of Japan, have
      suggested that environmental factors contribute to the pathogenetic process of
      ALS and parkinsonism-dementia (PD). Six Kii cases with ALS showed higher Ca and
      lower Mg contents in the central nervous system (CNS) tissues than those of
      neurologically normal controls. We subsequently designed an animal study to
      experimentally ascertain the mineral or metal deposition in CNS tissues under
      various dietary regimens using rats. The experimental results suggest that
      unbalanced minerals and/or metals lead to the accumulation not only of Ca, but
      also Mn, and Al, and diminution of Mg and Zn in CNS tissues of rats and humans on
      these dietary regimens, with implication for long-term neuronal degeneration and
      accumulating CNS deficit.

PMID- 15576967
TI  - [Effects of calcium channel blockers in atherosclerosis and cardiovascular event
      and oxidative vascular damage].
AB  - Ca antagonists are relevant therapeutic tool for patients with hypertension. The
      effects of Ca antagonists against oxidative vascular damage and followed
      atherosclerosis were elucidated in various experimental model accompanied with
      the vasodilatative effects of Ca antagonists by blocking the L-type Ca channel.
      The beneficial effects of Ca antagonists in cardiovascular disease have been
      demonstrated in several clinical trials, as we demonstrated the beneficial effect
      of Ca antagonist in the incidence of cardiovascular event in Japanese patients
      with coronary disease. In patient with diabetes mellitus, the cardiovascular
      disease was also caused by the mechanism involved with the increase in oxidative
      stress in blood vessels and related factors such as advanced glycation
      endproducts, protein kinase C and insulin resistance. The beneficial effects of
      Ca antagonists in cardiovascular disease in patients with diabetes mellitus have
      been demonstrated in several clinical trials, may be dependent on the effect of
      Ca antagonist against the oxidative stress in the setting of hyperglycemia.

PMID- 15576968
TI  - [Calcium channel blockers and atherosclerosis].
AB  - As changes in the calcium transport mechanisms contribute to cellular changes in
      atherosclerosis, it has been proposed that calcium channel blocker (CCB) may be
      effective in slowing the progression of coronary artery disease. CCBs possess
      anti-oxidative properties and protective effects on vascular cells. Randomized
      clinical trials including PREVENT and ELSA may establish a potentially new
      therapeutic role for third-generation dihydropyridinoline CCBs in the treatment
      of atherosclerosis.

PMID- 15576969
TI  - [Mechanism of vascular calcification].
AB  - Vascular calcification, especially in coronary artery not only serves as a
      surrogate marker for atherosclerosis, but also predicts a higher risk of
      myocardial infarction and death. Its pathogenesis involves an active
      mineralization process by chondrogenic and osteogenic cells as well as a passive
      precipitation of minerals. Since atherosclerosis is a chronic vascular
      inflammation, plaque calcification is conceptualized as a chondrogenic and/or
      osteogenic process associated with chronic vascular inflammation.

PMID- 15576970
TI  - [Statins, and the vascular and valvular calcification].
AB  - Statins are currently approved for reducing the risk of cardiovascular diseases,
      clinically. These evidences were thought to be due to the lipid-lowering effects
      of the statins. But recently, the growing evidences showed the various effects of
      statins, such as inhibition of vascular and valvular calcification. How statins
      affects the bone forming proteins and genes are still not known.

PMID- 15576971
TI  - [Bisphosphonates].
AB  - After the development of potent bisphosphonates including alendronate and
      risedronate, evidence has accumulated that not only vertebral but also non
      vertebral fractures can be prevented by these agents. In addition, numbers needed
      to treat for both vertebral and non-vertebral fractures by alendronate and
      risedronate are around 30 to 90. Thus, these agents are expected to improve the
      socio-economical situation of osteoporosis treatment as well as the survival and
      quality of life of osteoporotic patients. Once-a-week oral bisphosphonates and
      long-acting intravenous formula that can successfully inhibit bone resorption for
      3 months or longer are also under development. Although PTH and alendronate
      treatment in combination did not show much beneficial effects, there are results
      showing additive effect of sequential treatment with PTH followed by alendronate.
      From these studies, we can expect even better prospect for osteoporosis treatment
      by choosing from or sequentially combining these different modality of therapies.

PMID- 15576972
TI  - [Hormone replacement therapy].
AB  - Hormone Replacement Therapy (HRT) is replacement of depleted endogenous estrogen
      for postmenopausal women. Usually progestin is used in combination to avoid
      endometrial proliferation. As for bone metabolism, estrogens exert bone
      protective effect through inhibition of bone absorption. HRT has been shown to
      improve bone mineral density and to lower the risk of osteoporotic bone fracture.
      However, the results of recent large scale clinical studies in the U.S. indicate
      that HRT not only raise the risk of breast cancer, but also increase the
      incidence of atherosclerotic cardiovascular diseases. According to these studies,
      the benefit of HRT does not outweigh its risk except the treatment of
      postmenopausal vasomotor symptoms. To resolve this problem, low dose HRT and SERM
      (selective estrogen receptor modulator) regimens are under investigation.

PMID- 15576973
TI  - [Selective estrogen receptor modulator].
AB  - SERMs (selective estrogen-receptor modulators) selectively act on various target
      tissues under estrogen influence as estrogen-agonists or antagonists. Following
      publication of an interim report from the Women's Health Initiative (WHI)
      randomized trial, SERMs have drawn considerable attention as agents of interest,
      in that they allow almost all beneficial effects of estrogen to be retained while
      at the same time avoiding the harmful side effects associated with HRT. In this
      regard, raloxifene is reported to act on bone as an estrogen-agonist as does HRT
      thereby contributing to a significant decrease in the incidence of osteoporotic
      fractures, while, in contrast, acting on the breast as an estrogen-antagonist
      unlike HRT to reduce the incidence of breast cancer, and its further role is
      expected in the treatment of coronary heart disease. Thus, SERMs are emerging as
      a class of versatile agents with great potential, and their indications are
      expected to widen with further research evidence.

PMID- 15576974
TI  - [BMP and bone formation].
AB  - Bone Morphogenetic Proteins (BMPs) are secreted proteins that represent a group
      of the transforming growth factor-beta. BMPs were identified as molecules that
      induce ectopic bone formation in muscles of mice. The homo- or heterodimetric BMP
      proteins, which bind to serine/threonine protein-kinase receptor and activate
      smad and p38MAPK signal transductions, function as potent osteogenic factors. In
      vivo, it is not clear which BMPs play crucial roles in regulating osteogenesis.
      Clinical uses of rhBMP-2 and rhBMP-7 have been performed, but we need numerous
      rhBMPs, which is very expensive, to induce osteogenesis in humans.

PMID- 15576975
TI  - [Statins].
AB  - Statins are cholesterol-lowering drugs by inhibiting HMG-CoA reductase, which is
      a rate limiting enzyme in the mevalonate pathway. Recently, it has been shown
      that the mevalonate metabolites also play a role in the regulation of bone
      metabolism. In particular, a couple of years ago, an exciting discovery showing
      that statins stimulate bone formation in rodents was published. However, there
      have been great controversies in effects of statins on bone in human. Here we
      review the role of statins in bone metabolism, mainly focusing on clinical
      observations.

PMID- 15576976
TI  - [Serial review No.10. Calcium antagonist-improvement in the study of basic and
      clinical research: calcium antagonist and heart failure].

PMID- 15576977
TI  - [Serial review No.8. Dental embryology: microstructural formation of teeth].

PMID- 15576978
TI  - [Statin and bone metabolism].
AB  - 3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors (statins) are
      widely used for the treatment of hypercholesterolemia. Recent studies reveal that
      statins stimulate the bone formation, presumably through increasing the
      production of BMP-2, an important differentiation factor of osteoblast. Most, but
      not all, observational studies show that statin use is associated with a reduced
      rate of fracture. Randomized controlled trials are needed to judge the
      prophylactic effects of statins on fracture and their beneficial effects on
      surrogate markers for fracture, such as bone mass and bone turnover.

PMID- 15576979
TI  - [Leptin and beta-blockers in bone metabolism].
AB  - It has been shown that leptin, initially discovered as an anorexigenic hormone,
      exerts various biological effects. We demonstrated that leptin negatively
      regulates bone formation via the neuronal network composed of central nervous
      system and sympathetic nervous system. Administration of beta-blockers in mice
      led to an increase in bone mass. Moreover, recent report showing that beta
      blockers reduce the risk of fracture suggests their therapeutic application for
      osteoporosis.

PMID- 15576980
TI  - [Obesity and bone metabolism].
AB  - It is well known that obesity is associated with increased bone mineral density.
      Although this phenomenon has been explained to be attributable to the mechanical
      burden, there have been increasing evidences indicating that some humoral factor
      ie. 'hormone', especially adiposity signal such as insulin or leptin, may play a
      role in disorders of bone metabolism associated with obesity. There have been
      several evidences suggesting that other hormones such as thyroid hormone, growth
      hormone, or glucocorticoid may also be involved.

PMID- 15576981
TI  - [Diabetes and osteoporosis].
AB  - Since Albright first proposed the concept of "diabetic osteopenia", many studies
      have investigated the levels of bone mineral density (BMD) and the risk of
      osteoporosis in type 1 and type 2 diabetes. The presence of osteoporosis in type
      1 diabetes seems to be a reliable evidence. On the other hand, there is still
      some controversy about the risk of osteoporosis in type 2 diabetes probably due
      to different pathogenesis, clinical stage and environmental factors. Although
      details of the pathogenic mechanisms are not fully understood, low insulin
      secretion, insulin resistance, hyperglycemia, adipocytokines and other diabetic
      complications including diabetic triopathy may determine changes in diabetic bone
      metabolism. Recent findings suggest that several drugs for life style-related
      disease such as statins, beta blockers and thiazolidinediones may have a
      potential role to promote bone formation other than their own therapeutic
      effects.

PMID- 15576982
TI  - [Vascular endothelial cells and osteoblasts].
AB  - Bone has a variety of cells including osteoblasts and vascular endothelial cells.
      Evidence for interaction between these cells in bone has been accumulated. In
      this review, roles of vascular endothelial growth factor (VEGF) in bone are
      discussed. I refer to increase in osteoblastic VEGF production by statins, drugs
      for hypercholesterolemia, which possess promotion of bone formation. Moreover, I
      have mentioned the presence of bone-like tissue in atherosclerotic plaque.

PMID- 15576983
TI  - [PPARgamma and bone metabolism].
AB  - PPARgamma is a ligand-dependent nuclear receptor and regulates adipogenesis and
      associates with diabetes, obesity. Recently, relationship between PPARgamma and
      bone metabolism was investigated. Here, we report the molecular mechanism of
      PPARgamma transcriptional activity and the suppression of PPARgamma activity by
      cytokines in bone marrow-derived mesenchymal stem cells.

PMID- 15576984
TI  - [Ageing and bone].
AB  - Bone loss by ageing has been investigated from standpoints of systemic
      abnormality and some deficiency in osteoblastic bone formation. This seminar
      summarize the involvements of a key molecule of adipocytic differentiation PPAR
      gamma, essential IGF-I signaling molecules IRS-1 and IRS-2, and an anti-aging
      gene klotho in the pathophysiology of age-related osteoporosis.

PMID- 15576985
TI  - [Statin and BMP].
AB  - Bone morphogenetic proteins (BMP) are cytokines that promote differentiation of
      mesenchymal stem cells into differentiated osteoblasts and bone formation.
      Recently, HMG-CoA reductase inhibitors (statins) emerged as a candidate for the
      treatment of osteoporosis, because they stimulate BMP-2 expression and bone
      formation. Inhibition of Rho/Rho-kinase pathway may be involved in statin effect
      on bone formation.

PMID- 15576986
TI  - [The role of insulin receptor substrates in bone metabolism].
AB  - IRSs (insulin receptor substrates) are substrates for both insulin and IGF-I
      receptors. Insulin and IGF-I are known to be bone anabolic factors. IRS-1
      deficient mice exhibited severe low turnover osteopenia with decreased bone
      anabolic and catabolic action, while IRS-2 deficient mice showed osteopenia with
      decreased anabolic and increased catabolic action. IRS-1 signaling plays an
      important role for maintaining bone turnover while IRS-2 signaling maintains
      anabolic balance in osteoblasts.

PMID- 15576987
TI  - [Osteoporosis and gene polymorphism].
AB  - Osteoporosis is a multifactorial disease for which genetic and environmental
      factors are determinants. We have been conducting a candidate-gene approach in
      which polymorphisms of many bone metabolism related genes have been examined in
      the association study with bone mineral density and fracture incidence. However,
      the contribution of each gene is small and the major genetic determinants of BMD
      have not elucidated. Recently, a genome-wide systematic approach has been
      conducted to find the responsible genes using a genome-wide list of single
      nucleotide polymorphisms (SNPs). So far, several genes with higher statistical
      power have been screened out with this approach. The accumulating information of
      genome science will help understand the pathogenesis of osteoporosis and find the
      useful ways for the prevention and the treatment of this disease.

PMID- 15576988
TI  - [The effect of lifestyle factors on osteoporotic fractures].
AB  - Osteoporotic fracture is one of the biggest causes of bed-ridden conditions.
      Lifestyle factors such as dietary habits, smoking habits, alcohol consumption,
      and exercise habit are well associated with bone mineral densities. This review
      summarized the improved custom behavior is beneficial to prevent osteoporotic
      fractures in elderly.

PMID- 15576989
TI  - [Statins as possible therapeutic tools for osteoporosis].
AB  - Statins are cholesterol-lowering drugs as they inhibit HMG-CoA reductase, which
      is a rate limiting enzyme in the mevalonate pathway. Recently, mevalonate
      metabolites are also shown to play pivotal roles in the regulation of generation
      and function of osteoclasts and osteoblasts. However, there have been great
      controversies in effects of statins on bone metabolism, especially that on
      osteoporotic fractures in human. Here we briefly review the role of statins in
      bone metabolism through the survey of clinical observations.

PMID- 15576990
TI  - [Serial review No.11. Calcium antagonist-improvement in the study of basic and
      clinical research: calcium antagonist and hypertrophy of the heart].

PMID- 15576991
TI  - [Serial review No.9. Dental embryology: exchange of milk [baby] teeth].

PMID- 15576992
TI  - [Falls and fractures in elderly people, and life style for their prevention].
AB  - Approximately 10-20% of elderly people living in the community fall each year.
      And 5-10% of fall incidents result in a fracture and 0-2% of them result in a hip
      fracture. Several risk factors of falling and fracture are clarified and many
      preventive intervention programmes based on these risk factors have been
      established and evaluated. In this paper, these risk factors are reviewed and a
      lifestyle for the prevention of falling and fracture is discussed.

PMID- 15576993
TI  - [Trend of an osteoporosis curative medicine--Who uses what from when to when
      how?].
AB  - About the point of which medicine to use how in the medical treatment of
      osteoporosis, the large-scale clinical trial performed in Europe and America has
      been arranging. Especially, about calcium, vitamin D, estrogen, and
      bisphosphonates medicine can be used now based on the evidence about them. The
      necessity of medical treatment for the patient diagnosed as osteoporosis
      according to the criteria established by osteoporosis congress is guaranteed.
      However, when considering the necessity for prevention of osteoporosis, we would
      like to know the view about medicating osteopenia group, but there are few bases
      that for the moment it is important. Moreover, "up to when" in the point whether
      medical treatment is required, we have to wait for the report of the clinical
      test of medicine medication over a long period of time which is performed now.
      However, it is foundations to continue medicine medication as much as possible
      now, if effective. Although it became clear in estrogen medical treatment that a
      risk is higher than a benefit by medication examination over a long period of
      time, as well as this, It is necessary to discuss the benefit and the economic
      effect of an osteoporosis curative medicine.

PMID- 15576994
TI  - [The medical economic problem of the cost with the treatment for the fractures
      based on osteoporosis].
AB  - The fracture based on osteoporosis is increasing in the elderly population. The
      patient and his family suffer greatly from economic, mental and physical
      disadvantage during the treatment and the care. It is necessary about two million
      yen to treat one patient of the femoral neck fracture. But in the system of the
      health insurance, the patient over 75 years old does not have to pay about 50
      thousand million yen. The whole country, it will be necessary over fifty thousand
      million yen. The cost for the fracture based on osteoporosis is very terrible in
      the point of medical economic problem.

PMID- 15576995
TI  - [Practices and strategies for the prevention of falls in the osteoporotic
      elderly].
AB  - Among seniors with osteoporosis, falls can cause devastating injuries such as hip
      fractures even with only weak impacts. We have begun a combined medical
      examination and educational program for exercise to prevent injurious falls. To
      make fall prevention practices more widespread, we hold one-day simplified fall
      prevention program and instruction courses for practitioners.

PMID- 15576996
TI  - [Long-term care insurance system and osteoporosis].
AB  - The Long-term Care Insurance is the principal system that supports the Japanese
      elderly more than 24 million in number. The recipients of this system are
      increasing rapidly and get up to 3 million now. In Japan, hip fracture is one of
      the primary causes that make the elderly bedridden. In our study with the cases
      of hip fractures, 51.6% of the whole patients were self-reliant before fracture,
      but 25.6% one year after fracture. Keep it in mind that half of the self-reliant
      elderly will need support after fracture and encourage patients and their
      families to apply for certification of need for support.

PMID- 15576997
TI  - [Osteoporosis and living of residents in a nursing home].
AB  - Residents in a nursing home can become bedridden following fracture caused by
      osteoporosis or falls. To prevent fall and fracture is important, and conceived
      to reflect quality of caregiving in individual facilities. The incidence of
      falling is around 35% in all nursing homes related to our facility. Incidents of
      falling occur mostly during walking among ambulatory residents, and during
      performing transfers among residents using wheelchairs. Dementia is suggested to
      be a factor influencing the incidence of falling. In order to prevent fracture
      resulting from falling and osteoporosis in nursing homes, it is important that
      all working members in each facility examine prevention measures comprehensively,
      while considering characteristics of an environment of their facility and
      residents therein. All working members should thereby activity interven in the
      QOL (quality of life) of residents, and assist them to lead a healthy and joyful
      life n their nursing home.

PMID- 15576998
TI  - [Life with fear of falling after hip fracture].
AB  - Elderly people who experienced hip fracture often experience complicated
      psychological reaction as well as decline in physical functions. In order to
      avoid falls and re-fractures, they limit various activities resulting to
      worsening physical performance. This article reports perception among the
      community dwelling elders who experienced hip fracture, it includes quotation
      from the interviews conducted with focus clients. Elders were always worried
      about falling and some avoid the activities that were major cause of hip
      fracture. Also, they complained of feeling a foreign substance coming dull pain
      resulting from the bipolar hip prosthesis. They were also worried about being bed
      ridden so that they tried to expand their level of mobility, which tend to
      increase their risk of falling.

PMID- 15576999
TI  - [Importance of calcium and vitamin D intake in the childhood for the prevention
      of osteoporosis].
AB  - Bone stored a large amount of calcium. It is well known to the people who are
      engaged in medicine that the maximal bone mineral density in female is achieved
      at the age of 16. However, this evidence is not so familiar to the healthy
      Japanese. In this article, I emphasize that calcium and vitamin D intake are very
      important nutrients for preventing osteoporosis. I also propose that bone survey
      of the female students, who are attending to the junior high school or high
      school, will be important to find out the high risk group of osteoporosis in
      future.

PMID- 15577000
TI  - [Mortality and functional outcome of hip fractures in the elderly].
AB  - Recently, the incidence of osteoporosis and its related fracture are increasing
      as the aging of population has been progressing in most developed countries,
      becoming a serious medical and social problem. Among osteoporosis-related
      fractures, especially, hip fracture might have a marked influence on survival
      prognosis as well as a restriction of patient's daily activity and the bed-ridden
      status. Thus, clinical significance of hip fracture has been increasing, but
      particularly in the extreme elderly, it is difficult to manage patients in most
      cases because of the peculiarity due to their extreme old age. For example, hip
      fracture in the extreme elderly is characterized as follows: (1) It occurs easily
      with a slight external force. (2) It often associates various complications. (3)
      Its physical differences among individuals are considerably large. (4)
      Rehabilitation after surgery is difficult in many cases because of complicated
      dementia. and (5) It is difficult for the patients to live independently at home.
      This article reviews the literature on survival prognoses and functional results
      in the extreme elderly with hip fracture. The data from the literature indicate
      that in the extreme elderly, preoperative general condition, walking ability,
      type of fracture, and the type of surgery are likely to be the significant
      predictors of survival prognosis, whereas the degree of dementia seems to be the
      significant predictor of the recovery of walking ability.

PMID- 15577001
TI  - [Osteoporosis in the disabled].
AB  - Osteoporosis is a well-known complication of paralytic diseases. We investigated
      11 patients with chronic spinal cord injury who have been paralyzed for 20 years
      or more. History of fracture was searched in these 11 patients. Mineral density
      in the lower limbs was measured, and the bone metabolism was examined. Of the
      total of 8 fractures, 87.5% occurred in the relatively low muscle tonus group.
      Patients showed decreased bone mineral density of the femoral neck, and this was
      negatively correlated with period of paralysis. One female patient showed an
      abnormal rise in bone absorption markers. In this case, bisphosphonates can be
      effective to increase the bone mineral density. To prevent fracture in patients
      with paralysis, particular care should be taken in wheelchair operation and
      handling of the lower limbs.

PMID- 15577002
TI  - [Hip protectors for prevention of hip fractures in the frail elderly people].
AB  - There are good indications for the use of hip protectors in the elderly people
      requiring long-term care with high risks for falling and even better indications
      when such elderly also have risks for osteoporosis. Based on criteria for
      enrollment in randomized controlled trials, elderly who are eligible for long
      term care facilities but have not become bedridden should use hip protectors. The
      use of hip protectors as a preventive approach in long-term care facilities will
      successfully decrease the occurrence of hip fractures in such disabled elderly
      people.

PMID- 15577003
TI  - Preventing osteoporosis in every day life.
AB  - Osteoporosis is a condition characterized by low bone mineral density,
      microarchitectural deterioration of bone tissue, and a consequent increase in
      fracture risk. The public health impact of osteoporosis stems from its
      association with fractures of the hip, spine and forearm. Between 10 and 20
      percent of hip fracture patients die within a year of the event, and among those
      who survive, almost two-thirds remain disabled. The medical costs of osteoporosis
      and its attendant fractures have been placed at 5.2 billion dollars each year in
      the US and 615 million pound sterling each year in the UK. In Asia, osteoporosis
      is rapidly becoming a major public health problem with an increasing incidence of
      hip fracture and a rapidly aging population. By the year 2050, more than half of
      the hip fracture around the world would occur in Asia, with the total number
      approaching 3.2 million. Osteoporosis can be attributed to both genetic factors
      and environmental factors. While it is difficult to modify genes, much can be
      done to prevent osteoporosis in our every day life. These are discussed below.

PMID- 15577004
TI  - [Hormone replacement therapy and osteoporosis].
AB  - Estrogen deficiency is one significant cause of accelerated bone loss in women
      during and after menopause. Postmenopausal osteoporosis is a major health
      problem, primarily because of the severe morbidity and mortality associated with
      osteoporotic fractures. The Women's Health Initiative Study (WHI) reported that
      hormone replacement therapy (HRT) prevented osteoporotic fractures. The risks and
      benefits of HRT are complex and require the individual assessment of each woman
      considering taking HRT. Use of HRT can be considered as a treatment option for
      osteoporosis but the risks and benefits should be discussed with each individual
      woman before starting treatment.

PMID- 15577005
TI  - [QOL in osteoporotic patients with vertebral fractures].
AB  - Vertebral fractures leading to low back pain, spinal deformity, gastroesophageal
      reflux disease, and cardiopulmonary dysfunctions decrease the quality of life
      (QOL) in patients with osteoporosis. We had investigated the change of QOL in
      osteoporosis patients with back pain for 6 months. The relief of the pain
      improved "activities of daily living" , but did not "leisure, social activities"
      , "health perception" , "posture, figure" , and "fall, mental factors" . The
      control of pain and social approach such as fall prevention program are necessary
      to improve the QOL in patients with vertebral fractures.

PMID- 15577006
TI  - [Medication counseling in the oral medicine of osteoporosis and complications
      with elderly people].
AB  - Although long-term continuation medical treatment is needed in chronic diseases,
      such as osteoporosis, and hypertension, hyperlipemia, since there are no
      subjective symptoms much, an understanding of the necessity for medication is
      hard to be obtained. Furthermore, in elderly people, it has two or more chronic
      diseases, and since the medicine of varieties is taken in many cases, medication
      compliance tends to become bad. Explanation with a disease sufficient in a
      chronic-disease patient and medication counseling of elderly people is useful to
      improvement in compliance, and safety reservation of a patient.

PMID- 15577007
TI  - [Serial review No.12 Calcium antagonist-improvement in the study of basic and
      clinical research-Calcium and arrhythmia].

PMID- 15577008
TI  - [Serial review No.10 Dental embryology:Aging of enamel as biological mineralized
      tissues].

PMID- 15577009
TI  - [Case Report No.138:One case of advanced renal hyperparathyroidim complicated
      with acute renal failure].

PMID- 15577010
TI  - [Bone quantity and quality to its mechanical integrity].
AB  - Bone strength is made up of quantity (mass, mineralization), geometry (anatomy,
      micro architecture, collagen structure), and turnover/damage accumulation. While
      most of the mechanical behavior can be explained by measures of porosity, several
      additional descriptors of the geometry have been proposed for better predictions
      of fracture risk. This review introduces various aspects of these relationships
      between bone quantity and quality to its mechanical integrity.

PMID- 15577011
TI  - [Bone quality and bone metabolism (marker)].
AB  - NIH Consensus Development Panel states that bone strength primarily reflects the
      integration of bone density and bone quality. In addition, it is reported that
      bone quality refers to architecture, turnover, damage accumulation, and
      mineralization. Increased bone turnover is an independent risk of fracture of low
      bone mineral density. Increased bone turnover of urinary CTX, free DPD and free
      PYD, or decreased turnover of serum ICTP leads to increased relative risk of
      fractures in the femoral neck or spine/non-spine. Reduction of 50-70% in bone
      metabolic markers with therapy reduces fracture risk by 40-44%.

PMID- 15577012
TI  - [Bone quality in glucocorticoid induced osteoporosis].
AB  - The administration of oral glucocorticoids is associated with a significant
      decrease in bone formation (low turnover) and with generalized thinning of bone
      trabecula. These condition will be worse of bone quality and bone strength than
      high turnover state that indicate partial breakage of bone trabecula. Because the
      cut-off value of bone mineral density induced fracture is higher in
      glucocorticoid-induced osteoporosis than in postmenopausal osteoporosis.

PMID- 15577013
TI  - [Metabolic bone disease and bone quality].
AB  - On the progress of study concerned with pathology of metabolic bone disease such
      as osteoporosis, it has been known that most of bone strength can be explained by
      bone volume. As bone volume can be determine by bone mineral density (BMD) with
      dual-energy X-ray absorptiometry (DXA), it has been widely used for diagnosis of
      osteoporosis or efficacy of treatment. However, with the advance of bone
      morphometry, decrease of bone strength or existence of insufficiency fracture is
      influenced by not only loss of BMD but also deterioration of bone quality
      especially bone microstructure. In this chapter, we will give an outline of
      change of bone quality in metabolic bone disease.

PMID- 15577014
TI  - [Evaluation of bone quality in terms of degree of mineralization].
AB  - Quantification of degree of mineralization has recently drawn considerable
      attention as an evaluation method of bone quality. Degree of mineralization of
      bone is a main determinant factor for tissue material property of bone, and also
      closely associated with bone remodeling, fatigue process, and mechanical
      environment of bone.

PMID- 15577015
TI  - [Bone quality in the respect of bone matrix].
AB  - Bone is abundant in extracellular matrices, and therefore,"bone quality" appears
      to reflect the property of the bone matrix. The bone matrix is composed of
      minerals and organic materials. The volume of collagen fiber is approximately 90%
      of the whole organic materials of the bone matrix. Since collagen fibers could
      resist tension, the elasticity of the bone seems to come from the property of the
      collagen fibers. The mineralization of the bone matrix is achieved by the
      formation of hydroxyapatite crystals. The non-collagenous proteins and
      proteoglycans may regulate the growth of the mineralized crystal.

PMID- 15577016
TI  - [Microdamage and bone quality].
AB  - Fatigue occurs in every material under repetitive loading. Because bone is also
      being loaded under physiological condition, fatigue also occurs in bone and it is
      observed as microdamages under light microscope. However, in vivo bone is
      different from that ex-vivo. It is strongly suggests that in vivo microdamage is
      repaired by bone remodeling. Once generation and repair of microdamage is
      imbalanced, microdamage accumulates in bone and causes fatigue fracture.

PMID- 15577017
TI  - [Methods for assessing bone quality].
AB  - Bony quality, such as trabecular architecture and bone turnover, has
      conventionally been estimated by histomorphometric analysis of bone biopsy
      specimen. In recent years, these information can be obtained noninvasively by
      using CT, MRI, and biochemical markers. In the examination of bone specimen,
      several physical methods are newly utilized to assess the bone quality, providing
      detailed information on bone mineral and matrix protein.

PMID- 15577018
TI  - [Genes affecting bone quality].
AB  - Many genes have been shown to affect bone mass. However, because there have been
      only a few methods to evaluate bone quality, little is known about the genes that
      determine bone quality. Recently, several genes including collagen and vitamin D
      receptor genes have been shown to affect bone quality. With the establishment of
      methodology to determine bone quality more easily, we will learn much about the
      genes that affect bone quality in the near future.

PMID- 15577019
TI  - [Aging and bone quality].
AB  - At the research level, various factors have been correlated with changes in bone
      quality that underlie age-associated fragility. On the other hand, biochemical
      markers and imaging technology that can faithfully assess bone quality and are
      applicable to clinical practice remain to be developed.

PMID- 15577020
TI  - [Effects of vitamin D on bone quality].
AB  - The degree of increase BMD (bone mineral density) alone fails to account for the
      broader effectiveness of vitamin D in reducing the risk of fractures related to
      osteoporosis. The concept of bone strength also has evolved, integrating those
      traditional measures of bone quantity (mass) with more recently examined
      components of bone quality, for example, bone micro-architecture, degree of
      mineralization, accumulation of micro-damage, and bone turnover. In this review,
      the effects of vitamin D on bone quality, especially, on bone micro-architecture
      and degree of mineralization will be discussed.

PMID- 15577021
TI  - [Vitamin K and bone quality].
AB  - Dietary vitamin K intakes becomes reduced with aging. Low vitamin K intakes are
      associated with an increased incidence of hip fractures and an increase of under
      carboxylated osteocalcin in elderly men and women. The increase of under
      carboxylated osteocalcin is a risk factor for fractures in osteoporosis. Vitamin
      K2 treatment is effective for the prevention of fractures, but not for the
      increase of bone mineral density in osteoporosis. Vitamin K2 administration could
      be a potential treatment to improve the bone quality.

PMID- 15577022
TI  - [How do bisphosphonates improve bone quality?].
AB  - Accumulating evidence indicates that positive effects on bone mineral density of
      several promising drugs for osteoporosis do not completely account for their anti
      fracture effects. Among anti-osteoporosis drugs, effects of bisphosphonates on
      the reduction in fracture risk are well correlated with those on the increase in
      bone mineral density. Even in bisphosphonates, at most 50% of their anti-fracture
      effect is estimated to be independent of the increase in bone mineral density.
      This suggests that bisphosphonates improve bone quality composed of bone
      architecture, matrix composition and mineralization. Bone quality is an emerging
      issue to be explored with an investigation of bone biopsy specimen and 3
      dimensional structural analyses using micro computed tomography.

PMID- 15577023
TI  - [Bone quality and raloxifene].
AB  - Bone turnover affects fracture risk. Degrees of fracture risk reduction by
      antiresorptive agents are larger than those expected from the rates of BMD
      increase. Actually, fracture risk reduction by raloxifene is largely dependent on
      the effects of bone turnover regulation. Raloxifene stabilizes the trabecular
      structure, maintains the activities of micro-injury repair and healing of
      fracture, and increases the mean values of the degrees of tissue mineralization
      and the distribution of their ranges. The relationship between the fracture risk
      reduction and the changes in these parameters of bone quality is not clear.
      Further information is necessary based on the data of clinical practice.

PMID- 15577024
TI  - [Calcium channel blockers as therapeutic agents except for cardiovascular
      diseases].

PMID- 15577025
TI  - [Serial review No.11 Dental embryology: Aging phenomenon of enamel and dental
      pulp].

PMID- 15577026
TI  - [Case Report No.139:One case of esophageal cancer accompanied with low serum
      calcium and clouding of consciousness].

PMID- 15577028
TI  - [Principles and methodology of K/DOQI clinical guidelines].
AB  - NKF (National Kidney Foundation) launched the Dialysis Outcomes Quality
      Initiatives (DOQI) in 1995 and reported first guideline on dialysis therapy in
      Autumn of 1997. In 1999, DOQI was further developed into the Kidney Disease
      Outcomes Initiatives (K/DOQI), in which the target of clinical practice has
      included the entire phase of chronic kidney diseases (CKD). K/DOQI revised first
      guideline by DOQI in 2002 and also published the "Chronic Kidney
      Disease:Evaluation, Classification, and Stratification" in 2002 and "Proteinuria
      and Other Markers of Chronic Kidney Disease "in 2003, and then "Bone Metabolism
      and Disease in Chronic Kidney Disease" in the fall of 2003. These guidelines were
      prepared by working group and review team. For instance, the review team first
      searched 4,233 literatures and finally 467 relevant literatures was selected for
      citation as the basis of evidence. Based on the summary table of these
      literatures, working group prepared a draft guideline. Finally, the present
      guideline consists of 201 pages totally and reflects a dedicated effort by the
      team. K/DOQI has now started the effort to develop their guideline into truly a
      global one.

PMID- 15577029
TI  - [Outlines of K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease
      in Chronic Kidney Disease].
AB  - Recently "K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in
      Chronic Kidney Disease" was published. It consists of sixteen precise guidelines
      which cover the wide range of this field. It is expected that these guidelines
      contribute ESRD treatment in Japan in spite of some differences in medical
      practice for dialysis therapy between Japan and the United States. This article
      briefly summarizes the outlines of these guidelines.

PMID- 15577030
TI  - [K/DOQI clinical practice guidelines for management of renal osteodystrophy in
      predialysis patients].
AB  - Blood levels of PTH (parathyroid hormone) begin to rise when GFR falls below 60
      mL/min/1.73 m2, and evidence of bone disease due to hyperparathyroidism may be
      present at Stage 3 of chronic kidney disease (CKD). IntactPTH(i-PTH) is a useful
      test in detecting high turnover bone disorder and low turnover bone disorder. The
      Work Group taken target range of serum i-PTH in predialysis patients by their
      opinion. Dietary phosphorus should be restricted when the serum levels of i-PTH
      are elevated above target range of CKD stage. If phosphorus and i-PTH levels can
      not be controlled within the target range, despite dietary phosphorus
      restriction, phosphate binders should be prescribed. Only calcium based phosphate
      binders are available in predialysis patients in Japan. To avoid soft tissue
      calcification, total elemental calcium intake should not exceed 2,000 mg/day. If
      vitamin D deficiency are present, vitamin D2 should be supplied. But we can't
      measure serum 25(OH) D and prescribe vitamin D2 in Japan. Low dose of active
      vitamin D sterols are effective on renal osteodystrophy in predialysis patient.
      Active vitamin D sterols should be prescribed from low doses and serum calcium
      levels and renal function should be checked frequently. It is necessary to
      evaluate this K/DOQI (Kidney disease outcomes quality initiative) guideline and
      to establish guideline in Japan.

PMID- 15577031
TI  - [Treatment of bone disease in chronic kidney disease and in renal transplant
      recipients under K/DOQI clinical practice guidelines].
AB  - The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative
      (K/DOQI) provides evidence based clinical practice guidelines developed for all
      phases of kidney disease and related complications, from diagnosis to monitoring
      and management. Bone disease sets in during the early stages of Chronic Kidney
      Disease (CKD). Bone disease is observed in almost patients with chronic renal
      failure and after renal transplantation. Hyperparathyroid (high turnover) bone
      disease in patients with chronic renal failure is found most frequently followed
      by mixed osteodystrophy, low-turn over bone disease, and osteomalasia. Ninety to
      one hundred percent of kidney transplant patients have histological evidence of
      osteodystrophy and osteopenia (reduction of bone mass) following renal
      transplantation. Furthermore, osteoporosis is also appeared in many renal
      transplant recipients. After renal transplantation, renal osteodystrophy
      generally improves but bone mineral density (BMD) often worsens. When renal bone
      disease is assessed using a combination of biochemical markers, histology and
      bone densitometry, early intervention and carefully effective therapies might be
      reduced the morbidity associated with these common problems.

PMID- 15577032
TI  - [Pathogenesis of secondary hyperparathyroidism and renal bone disease].
AB  - Patients with chronic renal disease (CKD)almost always develop secondary
      hyperparathyroidism (SHPT) due to hypocalcemia, phosphate retention, and
      abnormalities in vitamin D (VD) metabolism. Concomitant decreases in VD receptor
      and calcium sensing receptor in the parathyroid glands render them more resistant
      to the action of VD and calcium, and accelerate parathyroid cell growth. Several
      types of bone diseases are known to occur in CKD patients. Excessive secretion of
      parathyroid hormone (PTH) due to SHPT causes high-turnover bone disease, called
      osteitis fibrosa. Among low-turnover bone disease (LTBD), osteomalacia which is
      characterized by calcification defect is often complicated with VD deficiency
      and/or aluminum accumulation. Recently, frequency of adynamic bone disease caused
      by PTH suppression, another type of LTBD, is increasing probably due to calcium
      salts as phosphate binder with or without VD treatment.

PMID- 15577033
TI  - [Diagnosis and classification of renal osteodystrophy].
AB  - Bone histomorphometry is essential to diagnosis of renal osteodystrophy. Sherrard
      et al classified renal osteodystrophy into the 5 groups according to Fb.V/TV,
      OV/BV and BFR/TV of cancellous bone (Osteitis fibrosa, Mixed uremic
      osteodystrophy, Osteomalacia, Mild lesion, Aplastic disease). In addition,
      because endocortical bone loss is generally irreversible, the evaluation of this
      region in the transiliac bone biopsy specimen also seems to be important.

PMID- 15577034
TI  - [Clinical evidence and treatment for optimum concentration of parathyroid
      hormone, calcium and phosphate in chronic renal failure].
AB  - Hyperparathyroidism, renal osteodystrophy and ectopic calcification, caused by
      hypocalcemia and hyperphosphatemia, are important complication in renal
      dysfunction, especially in end stage renal disease. Because it is the reason for
      reducing the survival rate and quality of life in these patients, it is important
      to control them from early stage in renal dysfunction. K/DOQI (kidney disease
      outcomes quality initiative) guideline shows us the recommended practical level
      and its account. It may be helpful for our daily clinical work.

PMID- 15577035
TI  - [The K/DOQI guidelines on diagnosis and treatment of aluminum bone disease in
      hemodialysis patients].
AB  - The presence of aluminum bone disease can be predicted by a rise in serum
      aluminum of > or = 50 microg/L following DFO challenge combined with plasma
      levels of intact PTH of < 150 pg/mL. However, the gold standard for the diagnosis
      of aluminum bone disease is a bone biopsy showing adynamic bone or osteomalacia.
      The dialysate concentration of aluminum should be maintained at < 10 microg/L and
      baseline levels of serum aluminum should be < 20 microg/L. In symptomatic
      patients with serum aluminum levels > 60 microg/L but < 200 microg/L or a rise of
      aluminum after DFO > 50 microg/L, DFO should be given to treat the aluminum
      overload.

PMID- 15577036
TI  - [Diagnosis and therapy for beta2-microglobulin amyloidosis in the K/DOQI
      guideline].
AB  - According to the Kidney disease outcomes quality initiative (K/DOQI) guideline,
      in order to decrease risk of beta2-microglobulin amyloidosis, noncuprophane
      (EVIDENCE), high-flux dialyzers (OPINION) should be used. No currently available
      therapy, except kidney transplantation, can stop disease progression of beta2
      microglobulin amyloidosis or provide symptomatic relief (EVIDENCE). Screening for
      beta2-microglobulin amyloidosis, including measurement of serum levels of beta2
      microglobulin, is not recommended (OPINION).

PMID- 15577037
TI  - [Mechanism and therapy of vascular calcification].
AB  - Vascular calcification is clinically important, because it predicts a higher risk
      of cardiovascular event. Its pathogenesis involve atherosclerosis and regulated
      by mechanism which like bone metabolism. In dialysis patients, there is excess
      oxidative stress, shortage of scavenger, metabolic abnormality of calcium and
      phosphate. These factors may accelerate vascular calcification in dialysis
      patient. K/DOQI guideline shows the therapeutic strategy for calcium and
      phosphate metabolic abnormality. It is expected more progression in therapy for
      vascular calcification.

PMID- 15577038
TI  - [Clinical application of calcimimetics].
AB  - Calcimimetic agents modulate the activity of calcium-sensing receptor on the
      surface of parathyroid cell and suppress the secretion of parathyroid hormone.
      Several clinical trials demonstrated that the second-generation calcimimetics
      cinacalcet HCl reduced PTH level, as well as Ca x P product in secondary
      hyperparathyroidism, while the agents reduced PTH and calcium level in primary
      hyperparathyroidism.

PMID- 15577039
TI  - [Biological activity of FGF-23 and pathophysiologic role in chronic kidney
      disease].
AB  - Recent studies indicate that FGF-23, which was originally identified as an
      endogenous causative factor for hypophosphatemic diseases, is a physiologic
      factor for the regulation of phosphate homeostasis and vitamin D metabolism. In
      patients with renal failure, serum concentrations of FGF-23 positively correlate
      with serum levels of phosphate, Ca-P product, and prathyroid hormone. It is
      plausible that increased FGF-23 levels are responsible for the reduction of
      1,25(OH)2D levels in the early stage of renal insufficiency and also involved in
      the development of secondary hyperparathyroidism in chronic and end-stage kidney
      disease.

PMID- 15577040
TI  - [Vitamin D deficiency/insufficiency in patients with chronic kidney disease stage
      3 and 4 -- current concept and its therapeutic strategy].
AB  - Vitamin D deficiency/insufficiency, which is clinically represented by low
      25(OH)D concentration, is frequently seen in patients with CKD stage 3 and 4.
      Although its cause is unknown, hypovitaminosis D is partly associated with low
      1,25(OH)2D in these patients, possibly leading to advancement of renal
      osteodystrophy. Recently, in United States, K/DOQI (Kidney disease outcomes
      quality initiative) guideline indicated that vitamin D deficiency/insufficiency
      of 25(OH)D concentration less than 30 ng/mL should be treated by supplementation
      of ergocalciferol. A Japanese guideline to treat vitamin D
      deficiency/insufficiency should be urgently established.

PMID- 15577041
TI  - [Front line of management of hyperphosphatemia in hemodialysis patients].
AB  - Management of hyperphosphatemia in hemodialysis patients is very important to
      prevent progress of renal hyperparathyroidism or ectopic calcification. Sevelamer
      hydrochloride is a Ca and Al free phosphate binder, and reduces serum phosphorus
      level, without any influence on serum Ca level, and Ca-P products. This compound
      is expected to reduce the incidence of arterial calcification, and improve the
      QOL (quality of life) of hemodialysis patients.

PMID- 15577042
TI  - [Vitamin D supplementation for chronic kidney disease according to the guideline
      issued by DOQI].
AB  - Supplementation of vitamin D in food is available in Japan, therefore, vitamin D
      deficiency is not likely to occur in our country. But, in the case of nephrotic
      syndrome and strict dietary protein restriction, low serum 25(OH)D level might
      develop in chronic kidney disease (CKD)patients. Guideline issued by National
      Kidney Foundation as DOQI recommend the use of vitamin D2 (ergocalciferol) when
      serum 25(OH)D level in CKD patients become less than 30 ng/mL. In addition, for
      the CKD patients with stage 5, the use of active vitamin D3 is recommended
      because a conversion to 1,25(OH)2D3, which is the most potent vitamin D, might be
      impossible in these patients. However, vitamin D2 product as a supplementary
      medicine is not available in Japan unfortunately. In this context, I try to
      explain the background of the recommendation of vitamin D2 for CKD patients.

PMID- 15577043
TI  - [Clinical practice guidelines for severe renal hyperparathyroidism].
AB  - Clinical practice guidelines for bone metabolism and disease in chronic kidney
      disease (CKD) proposed parathyroidectomy (PTX) in patients with CKD. As surgical
      indications, the guideline recommended that PTX should be performed in patients
      with severe hyperparathyroidism (persistent serum i-PTH > 800 pg/mL), associated
      with hypercalcemia and/or hyperphosphatemia that are refractory to medical
      treatment. However, the indications are not well defined and there are no studies
      to define absolute biomedical criteria. The clinical studies is needed to define
      appropriate indications for surgical treatment. It was confirmed that effective
      surgical therapy of severe secondary hyperparathyroidism can be accomplished by
      subtotal PTX or total PTX with autograft.

PMID- 15577047
TI  - [Bone quality in treatment with raroxifene ].
AB  - In recent years, treatments for osteoporosis have been developing rapidly, and
      many of these research results have been reported. Although the concept of EBM
      (evidence based medicine) is beginning to become widespread in Japan, the
      reliability of data can only be composed of reproducibility of trial results and
      quantitative consistency. Currently, one of trial results considered of
      possessing the highest reproducibility is the trial result from meta-analysis,
      which is a synthesis of all trials. Data used on the this meta-analysis is
      composed of up to 190 researches selected from approximately 2,000 categories of
      reports, and is the bottom line of osteoporosis treatment data over 25 years. It
      is believed that this will come forward as indispensable information when
      suggesting treatments to patients during the course of daily practice.

PMID- 15577048
TI  - [Interface science in formation of biominerals and biomolecules].
AB  - The prototype for the minerals in bone and teeth is usually considered to be the
      basic calcium phosphate hydroxyapatite (HA), containing impurities, such as
      carbonate and structural defects. It has been proposed that the biological
      apatite is formed via precursor phases, such as octacalcium phosphate (OCP). The
      initial precursors maturate with aging and may alter its surface property
      depending on the proceeding of the hydrolysis into HA regarding adsorption
      affinity for various biomolecules existing around the forming biominerals. The
      maturation of the biominerals could be modulating the process of additional
      mineralization after the initial mineral deposition happened within the hard
      tissues.

PMID- 15577049
TI  - [Control of calcification by extracellular matrix].
AB  - Physiological calcification begins from crystallization of hydroxyapatite in
      extracellular matrix of both bones and teeth. Because calcification is exactly
      the extracellular event, organic components of extracellular matrix play
      important roles in control of calcification. The authors discuss the molecular
      regulation of calcification by organic components of extracellular matrix,
      focusing on the mineral/organic interaction.

PMID- 15577050
TI  - [Regulation of bone mineralization by enzymes].
AB  - The enzymes, such as TNSALP regulate bone mineralization, and the mineralization
      inhibitor inorganic pyrophosphate (PPi) plays a central role in the process. NPP1
      and ANK increase PPi concentration in the extracellular matrix, while TNSALP
      hydrolyzes PPi. The analyses using knock-out mice demonstrated that NPP1 and ANK,
      and TNSALP are antagonistic regulators for PPi. Concerted regulation of PPi by
      TNSALP, NPP1, and ANK, leads bone mineralization to be regulated strictly.

PMID- 15577051
TI  - [Mineralization of dental hard tissues].
AB  - Tooth is a composite of the three different biological mineralized tissues
      (dentin, enamel, and cementum) that acquired supreme mechanical properties and
      function necessary for the mechanical digestion of the food throughout life. The
      underlining mechanisms of mineralization of each of these three components are
      unique and different from each other. Here the focus was placed on the
      mineralization process of dentin and enamel of the teeth of vertebrates.

PMID- 15577052
TI  - [Vascular calcification].
AB  - Vascular calcification is a pathological calcification process. Its pathogenesis
      involves active mineralization by chondrogenic and osteogenic cells. Since
      cartilaginous metaplasia has been found in several vascular diseases, this
      process may represent one of vascular remodeling in response to vascular injury.
      Endochondral ossification following cartilaginous metaplasia play an important
      role in the progression of vascular calcification.

PMID- 15577053
TI  - [Ossitication of the posterior longitudinal ligament of spine (OPLL)].
AB  - Ossification of the posterior longitudinal ligament of spine (OPLL) is a disease
      that causes ectopic ossification of the ligament to develop in the spinal canal.
      Although OPLL causes severe neurologic symptoms caused by spinal cord
      compression, the mechanisms of OPLL initiation and promotion have not yet been
      identified. It is a common disease with an incidence of 2-4% in the middle age
      and older populations of Asian countries, whereas lower incidence has been
      reported in non-Asian countries. The disorder is believed to be a collective
      result of heterogeneous etiopathologic factors affecting the spinal ligament.

PMID- 15577054
TI  - [New insights on plasma phosphate and calcium control].
AB  - The physiological regulation of renal Pi reabsorption is mediated by renal type
      II Na/Pi cotransporters. The type II a transporter is a key player of renal Pi
      reabsorption and regulated, among other factors, by parathyroid hormone (PTH).
      The PTH-induced inhibition of Pi reabsorption is mediated by endocytosis of the
      type II a transporter from the brush-border membrane and subsequent lysosomal
      degradation. In addition, during weaning, the type II c Na/Pi cotransporter
      (growth related Na/Pi cotransporter) is induced in the apical membrane of
      proximal tubular cells. The type II c transporter is also regulated by PTH, FGF
      23 and PHEX. Studying the mechanisms of the regulation of type II c transporters
      by PHEX and FGF-23 has increased understanding of the control of proximal tubular
      Pi handling and bone mineralization.

PMID- 15577055
TI  - [Mechanism of intracerebral calcification in hypoparathyroidism].
AB  - The mechanism of intracranial calcification in hypoparathyroidism, more
      frequently seen in pseudo--than idiopathic hypoparathyroidism, has not been
      completely elucidated, but may be related more to the duration of hypocalcaemia
      and hyperphosphatemia than parathyroid hormone itself. Hyperphosphatemia promotes
      ectopic calcification, especially in blood vessel and periarticular tissue in
      renal failure, but in brain tissue in hypoparathyroidism. Participation of PTH
      receptor2 in the brain and superoxide production by mitochondria in
      hypoparathyroidism should be explored with reference to intracerebral
      calcification and neurodegenerative diseases.

PMID- 15577056
TI  - [Regulation of calcification by bisphosphonates].
AB  - Etidronate, an analogue of first generation of bisphosphonates, has inhibitory
      actions on mineralization and hydroxyapatite crystal formation, which is
      therefore used as a drug to treat ectopic ossification in cases with total hip
      arthroplasty and spinal cord injury. The effect of bisphosphonates to prevent
      calcification could be associated with the physical property to attach tightly to
      hydroxyapatite crystals in bone matrix. A recent investigation suggested that
      bisphosphonates might prevent arterial calcification through a mechanism
      associated with the enhanced production of parathyroid hormone-related peptide
      from vascular smooth muscle cells. A derivative of bisphosphonates to inhibit
      vascular calcification in atherosclerosis is expected and should be developed in
      the near future.

PMID- 15577057
TI  - [Action of vitamin D on mineralization].
AB  - The effects of 1,25 (OH) (2)D on bone mineralization appear to be indirect by
      stimulating the calcium and phosphate supply, mainly by absorption from
      intestine. The disturbance in vitamin D action results in rickets in infancy and
      osteomalacia in adults. An association has been recently reported between mild
      vitamin D insufficiency and decreased bone mineral density in the elderly, which
      enhances the importance of appropriate vitamin D intake.

PMID- 15577058
TI  - [Regulation of bone mineralization by parathyroid hormone].
AB  - In randomized clinical trials, parathyroid hormone (PTH) showed potent anabolic
      effects on the lumbar spine and decreased the risk of incident vertebral
      fractures dramatically. Although the anabolic effect of PTH on cortical bone in
      the femoral neck is still unclear, it should be demonstrated in further clinical
      studies. Concurrent or sequential therapies of PTH and anti-resorptive agents
      will be one of the major issues of treatment for osteoporosis in the future.

PMID- 15577059
TI  - [Cause of death in dialysis patient--according to the survey of the Japanese
      Society for Dialysis Therapy].
AB  - Major causes of death in dialysis patients are heart failure, infection, cerebro
      vascular accident, malignancy, myocardial infarction, and cardiovascular
      disturbance; they are 43.7% of all causes of death. Hyperphosphatemia and
      increased calcium-phosphorus product aggravate ectopic calcification, and raise
      mortality rate. According to statistical data from the Japanese Society for
      Dialysis Therapy, calcium and phosphate levels recently decreased, because of
      progress of therapeutic agents and increase in aged people. But extreme decreases
      of them are also the risk factors of mortality, so appropriate control into the
      recommended range is necessary.

PMID- 15577060
TI  - [Atherosclerosis and vascular calcification in hemodialysis patients].
AB  - Cardiovascular disease is the largest cause of mortality in hemodialysis
      patients. Cardiovascular mortality is fivefold to twentyfold higher in
      hemodialysis patients than in the general population. Atherosclerosis and
      vascular calcification are the characteristic complications in hemodialysis
      patients. Hemodialysis patients have traditional risk factors such as abnormal
      lipid metabolism and uremia-related risk factors such as oxidative stress and
      hyperphosphatemia. Oxidative stress takes place by increased production of
      oxidants by leukocytes and antioxidant loss of vitamin C and E. Oxidatively
      modified LDL exist in the circulation by excess of oxidative stress in
      hemodialysis patients. Oxidative stress is a major contributor to accelerated
      development atherosclerosis. Oxidative stress and hyperphosphatemia also
      influence vascular calcification. The pattern of vascular calcification in
      hemodialysis patient is characterized by mineral deposition in the tunica media.
      It is reported that the obvious calcification in aorta and artery of the MGP
      knockout mouse is recognized. It is indicated that MGP has the inhibitory effect
      of the calcification of vessel wall. Vitamin E protects atherosclerosis and
      vascular calcification in hemodialysis patients. It is also important to control
      hyperphosphatemia for vascular calcification.

PMID- 15577061
TI  - [Mechanism of vascular calcification].
AB  - Vascular calcification in dialysis patients is associated with morbidity and
      mortality risks. Recent evidence suggests that vascular calcification is an
      active process resembling osteogenesis and chondrogenesis process. In this
      process, hyperphosphatemia is one of the important regulators. Inorganic
      phosphates directly regulate vascular calcification in vitro through a sodium
      dependent phosphate cotransporter and promote expression of the osteoblastic
      differentiation markers.

PMID- 15577062
TI  - [Evaluation and related factors in coronary artery calcification in chronic
      dialysis patients].
AB  - Electron beam CT (EBCT) has been used to measure coronary artery calcification
      score (CACS). We have been studied CACS on chronic dialysis patients and examined
      the relationship between CACS and laboratory variables, incidence of ischemic
      heart disease, and survival. High CACS is often observed in patients with high
      serum phosphate, high calcium phosphate product, and dyslipidemia. Several
      factors for calcification both stimulating and suppressing have been playing a
      role in chronic dialysis patients. CACS is a surrogate marker of adequate control
      of uremia.

PMID- 15577063
TI  - [Diagnosis of ischemic heart disease with coronary artery calcification score by
      electron beam computed tomography].
AB  - Coronary artery calcification score (CACS) by electron beam computed tomography
      (EBT) is determined as useful to access ischemic heart disease. Our study shows
      the availability of CACS by EBT among Japanese population as much as previous
      reports from abroad. Although EBT does not spread in Japan for less
      multipurposeness and good cost, multi-detector row CT which enables to measure
      CACS spread over Japan. It may be a useful tool for diagnosis of ischemic heart
      disease.

PMID- 15577064
TI  - [Evaluation of coronary artery calcification in ESRD patients].
AB  - Coronary artery calcification (CAC), observed in most end stage renal disease
      (ESRD) patients, has been reported to influence mortality and complications of
      cardiovascular diseases. Depend on the these reports, K/DOQI (Kidney Disease
      Outcomes Quality Initiative) guideline recommended to control serum Ca and
      phosphorus levels strictly in ESRD patients, in order to inhibit the progression
      of CAC. And then, we have been able to use new phosphate binder, sevelamer which
      dose not contain calcium and will able to use calcimimetics for secondary
      hyperparathyroidism as soon. Now, we should evaluate the diseases of bone as well
      as cardiovascular diseases according to the change of paradigms for renal
      osteodystrophy. It is undoubted that imaging methods play a main role on the
      management of CAC and coronary stenosis in end stage renal failure patients.
      Multidetector-row CT (MDCT) is a most useful imaging method, which has high
      temporal resolution and high spatial resolution. We may obtain adequate image
      quality for diagnosis and evaluate in 26 cases (87%), except for 4 cases not
      evaluated due to severe calcification. Therefore, this study suggested that 16
      row MSCT is useful as a screening test for coronary angiography (CAG) even in
      dialysis patients.

PMID- 15577065
TI  - [Sevelamer hydrochloride prevents ectopic calcification of blood vessels].
AB  - Sevelamer hydrochloride is a non-absorbed calcium- and metal-free phosphate
      binder that lowers the serum phosphorus levels in hemodialysis patients.
      Sevelamer contains multiple amines, which are partially protonated and interact
      with phosphate molecules through ionic and hydrogen bonding. We show the in vitro
      phosphate binding assay data and the efficacy of sevelamer to lower the serum
      phosphorus and calcium phosphorus product in several animal models. Furthermore,
      we indicate the vivid data that sevelamer prevented the ectopic calcification of
      aorta in adenine induced renal failure model, which represent severe
      hyperphosphatemia and the related dialysis complications.

PMID- 15577066
TI  - [Cardiac diagnostic techniques in dialysis patients].
AB  - The field of cardiovascular disease in patients with dialysis has seen a
      tremendous increase in the number and diversity of diagnostic techniques
      available. Therefore, the newer methods have added new types of information to
      our diagnostic area. The plain chest roentgenogram and electrocardiogram are
      still simple and important tests. The other noninvasive procedures such as
      echocardiography, radionuclide techniques, CT and MRI supply important additional
      information concerning cardiac anatomy and function, but invasive cardiac
      catheterization remains the only method for accurately measuring intracardiac
      pressures and cineangiography is still necessary for defining the anatomy of the
      coronary arteries. Recently, the determination of natriuretic peptides (ANP,BNP),
      noradrenaline and troponin is added to evaluate cardiac function. The purpose of
      this paper discusses the use of these techniques in patients with dialysis.

PMID- 15577067
TI  - [Treatment of coronary artery disease in hemodialysis patients].
AB  - Coronary artery disease is important in patients with hemodialysis because it
      relates with prognosis. Characteristics of coronary lesions are severe
      calcification, diffuse disease and multi-vessel disease. Coronary artery bypass
      is effective to improve long-term prognosis; however, non-cardiac complication
      rate is high. Percutaneous coronary intervention is also effective but rotablator
      is required for severe calcified arteries. Complete revascularization can improve
      long-term prognosis.

PMID- 15577068
TI  - [Serial review No.13. Dental embryology: regeneration of teeth].

PMID- 15577069
TI  - [Case report No.142: large cell lung cancer accompanied by remarkable
      leukocytosis and hypercarcinoma].

PMID- 15577070
TI  - [Cartilage proteoglycan aggregate: structure and function].
AB  - The proteoglycan aggregate is the major structural component of the extracellular
      matrix of the cartilage, composed of aggrecan, hyaluronan (HA) and link protein
      (LP). The aggregates provide cartilage with unique gel-like property and
      resistance to deformation through water absorption. Natural knockout mice of
      aggrecan, termed cartilage matrix deficiency, and LP-null mice exhibit decreased
      levels of aggrecan depositon in cartilage and correspond well with their
      phenotypes such as dwarfism and spinal misalignment, demonstrating in vivo roles
      of the aggregate in cartilage development and homeostasis. Our recent studies
      demonstrate that versican/PG-M, another member of aggrecan family with a similar
      domain structure, binds both HA and LP, forming an aggregate. Further functional
      analyses of domains and subdomains showed distinct interaction of versican/PG-M
      with LP from aggrecan, suggesting that the versican/PG-M aggregate may have
      different function in cartilage.

PMID- 15577071
TI  - [Molecular mechanisms of cartilage formation and chondrocyte maturation].
AB  - Cartilage plays multiple roles in vertebrate animals. In an embryonic stage and
      early postnatal life, cartilage is important not only as a structural support of
      early embryo but also as a template of endochondral bone. In a later postnatal
      life, cartilage provides smooth joint movement and tissue elasticity. A number of
      critical signaling molecules that regulate cartilage formation and chondrocytes
      maturation in endochondral bone formation have been identified to date. The
      interplay of those important molecules is also actively studied. However, several
      fundamental questions still remain unsolved. What signal initiates mesenchymal
      cell condensation? Does condensation enough to make cells competent for BMP
      induced chondrogenesis? Is there chondrocyte stem cell in cartilage? Likewise, it
      is not known which factor triggers chondrocytes maturation. In this review
      article, we summarized the action of several key factors including BMP, hedgehog,
      PTHrP, and Wnt in condensation, chondrogenenic differentiation and maturation of
      chondrocytes. Towards further understanding of above fundamental questions, this
      review article also tried to propose future direction of cartilage biology
      research.

PMID- 15577072
TI  - [Biology of articular cartilage repair--present status and prospects].
AB  - The cartilage response to injury differs from the classic wound healing because
      of two important features of the cartilage structure; lack of vascular system and
      rich matrix preventing chondrocyte from migration to the injury site. Three
      distinct types of cartilage injuries can be identified based on the depth of
      injury and the repair response: microdamage, chondral injury, and osteochondral
      injury. There have been numerous attempts to repair cartilage injury, however
      their results have reinforced that articular cartilage has limited potential to
      repair itself. However, current research is helping to clarify the mechanism of
      cartilage injury and repair based on its gene expression. Biology, gene therapy,
      and tissue engineering may provide a breakthrough to treat cartilage injury.

PMID- 15577073
TI  - [Cartilage and mechanical stress from the point of the view of development,
      growth, pathology and therapeutic aspects].
AB  - Articular cartilage is always subjected to various types, magnitudes and cycles
      of mechanical stress. While it has been recognized that these stresses regulate
      the chondrocyte growth and differentiation, the mechanism is still unclear. Here,
      we summarize the effect of mechanical stress on cartilage metabolism from the
      point of view of development, growth, pathology and therapeutic aspect.

PMID- 15577074
TI  - [Role of aggrecanase and MMP in cartilage degradation].
AB  - Aritcular cartilage damage results in degradation of macromolecular in cartilage
      tissue such as aggrecan and type II collagen that are mediated with aggrecanases
      and matrix metalloproteinases. As the activity of MMP-13 against Type II collagen
      is very strong, so it plays significant role in cartilage collagen degradation.
      However, it is noteworthy that the inhibition of both aggrecanse-1. 2 can prevent
      cartilage degradation. Aggrecan hydrates the collagen network and provides the
      cartilage tissue with its characteristic pressibility and elasticity. It become
      now clear that aggrecan plays protective role in preventing degradation of
      collagen fibrils. Aggrecan and type II collagen molecules cooperatively maintain
      the cartilage integrity and function.

PMID- 15577075
TI  - [Morphological features of articular cartilage and synovial membrane in
      osteoarthritis and rheumatoid arthritis].
AB  - Osteoarthritis (OA) and rheumatoid arthritis (RA) do not show any specific
      morphological findings. However, there are many morphological findings which are
      common to each disease. In the current study, we describe morphological changes
      of articular cartilage and synovial membrane during progression of joint
      destruction in OA and RA, respectively.

PMID- 15577076
TI  - [Role of BMPs and Smads during endochondral bone formation].
AB  - Biochemical research has revealed that BMP signals are mainly mediated through
      ligand binding to the receptors followed by activation of Smad proteins. BMP
      signaling is subjected to regulation at extracellular level by noggin and at
      intracellular level by inhibitory-Smads. Analysis of transgenic mice in which BMP
      signals are activated or inactivated has been clarifying a role of BMP signaling
      during endochondral bone formation. BMPs promote chondrocyte proliferation and
      hypertrophy, whereas Smad signaling regulates chondrocyte hypertrophy. Proper
      regulation of these signals is necessary for normal bone formation.

PMID- 15577077
TI  - [Proteoglycan knock-out mice and osteoarthritis].
AB  - There are several types of small leucine-rich proteoglycans expressed in
      articular cartilage and its surrounding tissues. Many of these proteoglycans are
      functioning as a modulator of collagen fibrillogenesis via binding to the surface
      of collagen fibers. Therefore, deficiencies of their expression in knock-out mice
      often result in the formation of abnormal collagen fibers leading to the
      instability of the join, and finally trigger osteoarthritis.

PMID- 15577078
TI  - [Characterization of intervertebral disc--disc cells and pericellular
      microenvironment].
AB  - The intervertebral disc is classified as fibrocartilage, and has distinct
      functional and mechanical properties. The disc, composed of the nucleus pulposus
      and annulus fibrosus, varies in density, anatomic features, and in the morphology
      of their constituent cells. This heterogeneity has hampered detailed
      investigations of disc cellular metabolism. Focusing on the heterogeneity, we
      cultured disc cells under various conditions to examine the cellular metabolism,
      specifically glycosaminoglycan accumulation and pericellular microenvironment,
      and succeeded in mechanically isolating disc chondrons from annulus fibrosus. We
      believe that disc chondron also plays an important role in maintaining
      cartilageous phenotype in terms of cell-matrix interaction of the intervertebral
      disc.

PMID- 15577079
TI  - [Relationship between gene transfer and cartilage tissue engineering].
AB  - Injury to the articular cartilage occurs under various pathological conditions
      such as trauma, inflammation and aging and is followed by osteoarthritic changes
      of the affected joints. Recently, some studies have revealed that enough
      chondrogenic proliferation was required using some factors such as TGF-beta and
      BMPs. We, also, have reported that synovial tissues include multipotent
      mesenchymal stem cells, which can differentiate into chondrocytes. These results
      suggest that not only are synovial cells a good therapeutic target of
      inflammatory joint diseases, but also can be utilized for tissue engineering of
      cartilage.

PMID- 15577080
TI  - [BMP and LMP-1 for intervertebral disc regeneration].
AB  - Some evidence indicates that intervertebral disc degeneration is associated with
      decreasing of matrix synthesis from disc cell. BMP-2 increased mRNA of aggrecan
      and Type II collagen. It also enhanced disc matrix (proteoglycan) production.
      Adenovirually mediated LMP-1 overexpression in intervertebral disc cells
      increased disc cell proteoglycan production through BMP-2 and BMP-7 mediated
      process.

PMID- 15577081
TI  - [Tissue engineered cartilage for biological repair of cartilage defects].
AB  - Recent developments in tissue engineering techniques in cartilage repair were
      discussed. Recently, the novel two-step method, the alginate-recovered
      chondrocyte method (ARC method), which does not require the aid of an exogenous
      synthetic matrix, was developed. The first step of this method consists of
      culturing phenotypically stable chondrocytes under conditions optimal for the
      formation of a proteoglycan-rich cell-associated matrix (CM) in alginate beads.
      Then, the cells with their CM are recovered from the alginate and allowed to
      rapidly integrate into a solid mass of tissue on a culture insert with a porous
      membrane. The use of a growth factor, recombinant human osteogenic protein-1 (OP
      1) maximized the formation of tissue engineered cartilaginous tissue from adult
      human articular cartilage. Using the ARC method, the enhancement of matrix
      formation by OP-1 will produce a larger volume of tissue-engineered cartilage to
      cover large defects.

PMID- 15577082
TI  - [Treatment of lumbar intervertebral disc displacement with chondroitinase ABC-
      experimental basis for clinical application].
AB  - After single intradiscal injection of C-ABC in rabbit inter-vertebral discs,
      water content in the matrix of nucleus pulposus diminished clearly. After similar
      injection of C-ABC in sheep discs, disc inner pressure was diminished. After
      single intradiscal injection of C-ABC in dog inter-vertebral discs suffering disc
      herniation, the syndromes coming from the herniation diminished or disappeared.
      Based on these observations C-ABC is expected to be a chemonucleolytic agent and
      a human clinical trial is now in progress.

PMID- 15577083
TI  - [Role of cleavage of type II collagen by collagenase in osteoarthritis and its
      progression].
AB  - Now, the biomarker for bone metabolism have important role on treatment of
      osteoporosis. It is important to develop the reliable biomarker to detect the
      early stage of osteoarthritis. The biomarker could be useful tool not only to
      study what exercise is good for the treatment and prevention of progression of
      osteoarthritis but also to develop new drug therapy. We focused on role of
      cleavage of type II collagen by collagenase in osteoarthritis with immunoassay
      for the specific cleavage site.

PMID- 15577084
TI  - [Articular cartilage repair with cell transplantation].
AB  - Articular cartilage has a limited capacity for repair. Repair of articular
      cartilage has been an important theme for orthopaedic surgeons. With the progress
      of tissue engineering in the treatment of articular cartilage injury, we can
      obtain good results, to some extent, by cell transplantations. This review
      summarized the present status of the treatment of articular cartilage injuries by
      cell transplantations.

PMID- 15577085
TI  - [Intra-articular injection of hyaluronan for the treatment of knee
      osteoarthritis].
AB  - Osteoarthritis, involves mainly in the knees, is a disease characterized by a
      mixture of degradative and reparative processes in the articular cartilage. Many
      compounds have been used intra-articularly. Of those, corticosteroids are very
      potent anti-inflammatory agents. Although intra-articular injections have been
      used for the symptomatic treatment of osteoarthritis, corticosteroids injections
      may suppress cartilage proteoglycan synthesis, worsen cartilage lesion, or even
      cause degenerative lesions in normal cartilage. Viscosupplementation is a novel,
      safe, and possibly effective form of local treatment for osteoarthritis. It aims
      at supplying replacement hyaluronic acid into the joint space to return the
      elasticity and viscosity of the synovial fluid to normal. Hyaluronic acid, a
      polysaccharide, is a natural component of cartilage and plays an essential part
      in the viscoelastic properties of the synovial fluid. Although there is still
      insufficient information to permit a conclusion concerning the effect of this
      treatment, if any, on the progression of osteoarthritis in humans, considerable
      evidence supports the positive effects of hyaluronic acid on joint cellular and
      immunological function.

PMID- 15577086
TI  - [Joint destruction and matrix metalloproteinases--regulation by pharmacologic
      inhibitors and growth factors].
AB  - Matrix metalloproteinase (MMP) plays an important role in degradation of
      cartilage matrix. The expression of MMPs in cartilage or syovial membrane was
      increased in osteoarthritis or rheumatoid arthritis. We summarized the regulation
      mechanism of MMP production, and described pharmacologic inhibitors such as non
      steroidal anti-inflammatory drugs, steroid and growth factors, which might be
      useful to prevention of joint destruction.

PMID- 15577087
TI  - [Case report--total hip arthroplasty after femoral osteotomy].
AB  - Osteoarthritis that is the most common cartilage disease is difficult to treat
      conservatively. Usually it is treated by operative therapy. Osteotomy and
      arthroplasty are the popular operation. Osteotomy has a problem of unstable
      results. Some patients need arthroplasty after osteotomy, cause of getting worse
      of pain. It is difficult to operate arthroplasty for deformity of proximal femor
      after osteotomy. We report arthroplasty using ROBODOC is easy to operate
      cementless hip arthroplasty after osteotomy.

PMID- 15577088
TI  - [Difficult cases of total knee arthroplasty].
AB  - We report two difficult cases in total knee arthroplasty (TKA). One is an
      arthritis mutilans knee with large tibial bone deficiency that required TKA using
      tibial metal wedge augmentation. Another is a post-traumatic OA knee with varus
      deformity and rotational malalignment that had TKA by the ROBODOC system.

PMID- 15577089
TI  - [Case of pseudo-hypoparathyroidism type II with Basedow's disease].

PMID- 15577090
TI  - The role of magnesium in traumatic brain injury.
AB  - In Japan, over 5,000 deaths per year are a result of traumatic brain injury (TBI)
      with most being due to motor vehicle accidents. Survivors of TBI number into the
      hundreds of thousands and are often left with debilitating neurological deficits.
      Recently it has been identified that much of the brain damage after TBI develops
      over time with the primary injury initiating a secondary injury cascade made up
      of deleterious pathophysiological and biochemical reactions. The delayed
      development of secondary injury creates an opportunity for therapeutic
      intervention and considerable effort is being directed toward identifying the
      secondary injury factors and developing interventions that may potentially
      prevent their actions. Several secondary injury factors have been identified
      including oxidative stress, changes in blood flow, neurotransmitters and ionic
      changes, oedema and energy failure. Of these, Mg(2+) decline has been identified
      as playing a crucial role in the secondary injury process, in part because of its
      central role in the regulation of a large number of other known injury factors.
      This brief review will summarize the experimental evidence supporting a critical
      role of Mg(2+) in the pathophysiology of TBI, and will examine the use of
      magnesium salts as a therapeutic intervention.

PMID- 15577091
TI  - Experimental cerebral ischemia and magnesium.
AB  - Cerebral ischemia engages multiple terminal pathways involving the loss of ionic
      homeostasis, and acute and delayed neuronal damage. Several studies have focused
      on the derangement of energy metabolism and calcium, but not on magnesium.
      Hypomagnesium or low dietary magnesium intake may increase the risk of stroke and
      other cardiovascular diseases. The neuroprotective effects of magnesium have been
      attributed to a variety of effects on pathophysiologic mechanisms during and
      after cerebral ischemia, such as antagonizing calcium-mediated metabolic
      processes, inhibition of the N-methyl-D-aspartate (NMDA) receptors and relaxing
      vascular smooth muscles. Systemically administered magnesium provides beneficial
      effects in both clinical patients and cerebral ischemic animal models. Magnesium,
      as one of the therapeutic agents in stroke treatment, has the advantages of being
      inexpensive, widely available, and causing few side effects. The optimal doses
      for the treatment of cerebral ischemia both in animal models and in humans have
      not been defined yet. Thus, we attempted to evaluate the effects of magnesium on
      experimental cerebral ischemia.

PMID- 15577092
TI  - [Fluorescent probes for intracellular Mg2+ measurement].
AB  - Recently, fluorescent probes are widely used as tools for dynamical measurement
      of ion distributions and concentrations in cells. They are highly sensitive, and
      offer imaging by the use of fluorescent microscopy in easily and less cell
      damaging way. This paper discusses the selectivity and optical character of the
      three novel Mg(2+) fluorescent probes. KMG-20AM offers ratiometric quantative
      measurement of Mg(2+), KMG-104 provides high-sensitive qualitative analysis and 3
      D measurement. With those improved Mg(2+) fluorescent probes, the physiological
      and pathological role of Mg(2+) are going to be more and more clear.

PMID- 15577093
TI  - [Effect of magnesium on neural activities in vitro].
AB  - It has been well known that magnesium ion (Mg(2+)) plays an important role in
      biological functions, especially in neural activities and functions. However, not
      so many researches have been carried to this subject. Here we investigated the
      Mg(2+)effect on neuronal electrical activities together with NMDA receptor and
      synaptic glutamate release by using Multi-Electrode Array (MEA) and Enzyme
      modified MEA-based multi-array sensor.

PMID- 15577094
TI  - [Transport of Mg2+ by Na+-Mg2+ exchange].
AB  - Intracellular free Mg(2+) concentration is maintained at low levels by active
      extrusion from the cells. One of postulated mechanisms is the Na(+)-Mg(2+)
      exchange, which extrudes Mg(2+) in exchange with Na(+) influx. Although the Na(+)
      Mg(2+) exchange activity has been reported in many types of cell, including
      neurons, details of molecular mechanisms are only poorly understood. In this
      chapter, we briefly will review our current knowledge on [1] stoichiometry of the
      Na(+)-Mg(2+) exchange, [2] interaction between the Na(+)-Ca(2+) exchange and the
      Na(+)-Mg(2+) exchange, [3] molecular biology of the Na(+)-Mg(2+) exchanger.

PMID- 15577095
TI  - [Simultaneous Fluorescent Imaging of Mg2+ and Ca2+].
AB  - Simultaneous fluorescent imaging technique with several indicators is a powerful
      bio-imaging tool for a comprehensive survey about molecular functions in living
      cells. There are several interactions between Mg(2+) and Ca(2+) such as a counter
      transport or a competition at binding sites of divalent cation. To measure Mg-Ca
      images simultaneously, indicators with high selectivity to each divalent cation
      and multi-color fluorescent imaging system are essential. Here we introduce a
      setup for Mg-Ca fluorescent imaging we construct, and some reports about Mg-Ca
      imaging.

PMID- 15577096
TI  - [Function and toxicity of trace metals in the central nervous system].
AB  - Trace metals such as zinc, manganese and iron usually serve the function of
      metalloproteins in neurons and glial cells, while a portion of trace metals
      exists in the presynaptic vesicles, and may be released with neurotransmitters.
      Zinc released into the synaptic cleft may serve as an inhibitory neuromodulator
      of glutamate release in the hippocampus, while neuromodulation by other trace
      metals such as manganese and copper might mean both functional and toxic aspects
      in the synapse. Dietary zinc deficiency affects zinc homeostasis in the brain,
      followed by an enhanced susceptibility to excitotoxicity of glutamate in the
      hippocampus. The homeostasis of trace metals in the brain is important for brain
      function and also prevention of brain diseases.

PMID- 15577097
TI  - [Physiological role of Mg2+ in neurons].
AB  - Physiological role of Mg ions in living cells is now in the process of
      reexamination. This is triggered by the finding that cytoplasmic Mg(2+)
      concentration measured by a fluorescent dye, mag fura-2, is surprisingly small,
      being not more than 1 mM. Lines of examination have revealed that Mg(2+) inhibits
      various species of ionc channels not only from outside but also from inside of
      the plasma membrane. Entry of Mg(2+) into intracellular space is revealed to take
      place via a Ca(2+)-channels, TRPM7; this channel may thus be called "Mg(2+)
      channel". Moreover, an excess amount of intracellular Mg(2+) induced by hyper
      activity of NMDA channels occasionally causes neuronal cell death as a result of
      inhibitory effects of Mg(2+) to mitochondrial activities.

PMID- 15577098
TI  - [Neuroprotective effects of magnesium on cerebral ischemia and cerebral
      contusion].
AB  - Neuroprotective effects of magnesium (Mg(2+)) have been shown in experimental
      studies by using animal models of the cerebral ischemia and cerebral contusion.
      We review the neuroprotective effects of Mg(2+) in the histological and
      behavioral studies. In the animal models of cerebral ischemia, Mg(2+) treatment
      reduces the infarct volume, inhibits the neuronal death, and attenuates the motor
      impairments. In the animal models of cerebral contusion, Mg(2+) treatment
      inhibits the neuronal death and edema, and attenuates not only the motor
      impairments but also cognitive dysfunction.

PMID- 15577099
TI  - Magnesium therapy and recovery of function in experimental models of brain injury
      and neurodegenerative disease.
AB  - The role of magnesium (Mg(2+)) in brain injury has been well established. The
      present paper reviews the use of Mg(2+) therapy to facilitate recovery of
      function in a focal model of brain injury. Specifically a summary of the ability
      of magnesium chloride (MgCl(2)) to induce recovery of chronic behavioral
      impairments and the establishment of MgCl(2)'s wide therapeutic window is
      presented. These results suggest that Mg(2+) therapy is effective in facilitating
      recovery of function and exhibits very robust and unique effects.

PMID- 15577100
TI  - [Magnesium deficiency--benefits of "life salt nuti ma-su"].
AB  - One of essential minerals magnesium tastes bitter, so human love to remove
      magnesium from salt. But magnesium is also essential for cell functions in the
      body. Salts are getting purifying only NaCl from sea water. It means other
      minerals are gone out. So other essential minerals easily are getting to
      deficiency in the body. Recently the technique of purification of salt from sea
      water has developed. But the contents of magnesium other than [NaCl] is getting
      decrease. So deficiency symptom is easily occurred. The important role of
      magnesium is control of higher function of nervous system, behavior, memory and
      learning in the human. So we have to intake a lot of magnesium from many kinds of
      salts including sea water.

PMID- 15577101
TI  - [Role of magnesium ions on the regulation of NMDA receptor--a pharmacopathology
      of memantine].
AB  - Magnesium ion blocks the ion channel of the NMDA receptor at a stable condition.
      The ion channel competes with the binding site of the noncompetitive antagonists
      phencyclidine (PCP) and MK-801, which prevent a brain impairment due to the
      ischemia and so on. The binding ability of these antagonists is strong, an
      exchange with the magnesium ion is not easy, then the side effect of the
      schizophrenia-like behavior is caused. Recently, memantine can be used as a
      therapeutic drug of the moderate-to-severe Alzheimer's disease. Memantine is the
      noncompetitive antagonist, too, then those development details and a difference
      from MK-801 were explained.

PMID- 15577102
TI  - [Characterization of SN-6, a novel exchange inhibitor and its renal protective
      effect].
AB  - Recently, we developed 2-(4- [4-nitrobenzyloxy] benzyl) thiazolidine-4-carboxylic
      acid ethyl ester (SN-6), a newly synthesized and selective inhibitor of
      Na(+)/Ca(2+) exchanger. SN-6 is a selective inhibitor for the Ca(2+) influx mode
      of Na(+)/Ca(2+) exchanger. And this compound attenuated hypoxia/reoxygenation
      induced renal tubular cell damage and ischemia/reperfusion-induced renal failure.
      These results suggest that SN-6 is expected to be pharmacological tools to study
      the roles of the exchanger and a new anti-ischemic drug.

PMID- 15577103
TI  - [K/DOQI clinical practice guidelines for bone metabolism and disease in CKD].
AB  - K/DOQI (Kidney Disease Outcome Quality Initiative) Clinical Practice Guidelines
      for Bone Metabolism and Disease in Chronic Kidney Disease were published last
      year. The Work Group screened enormous amount of articles and made up of sixteen
      guidelines for Bone metabolism and disease in Chronic Kidney Disease. This review
      provides brief an overview of guidelines with strong emphasis on vitamin D.

PMID- 15577104
TI  - [Role of vitamin D in the pathogenesis of renal osteodystrophy].
AB  - Renal osteodystrophy was occurred in patients with chronic renal failure and the
      biopsied patients had various forms of bone disease. Active vitamin D has an
      important role of calcium regulation and bone metabolism. In patients with end
      stage renal disease, decreased levels of active vitamin D, reduced number of
      vitamin D receptors and calcium sensing receptors in parathyroid gland pay a
      major role in the development of hyperparathyroidism. It was invited osteitis
      fibrosa, high bone turnover. The parathyroid function is suppressed by active
      vitamin D, it was considered that lower parathyroid hormone levels was one of the
      cause of low bone turnover, adynamic bone disease.

PMID- 15577105
TI  - [Vitamin D therapy in renal osteodystrophy].
AB  - In Japan, three oral preparations (calcitriol, alfacalcidol and falecalcitriol)
      and two intravenous preparations (calcitriol and maxacalcitol) are now available
      for the vitamin D(3) therapy in renal osteodystrophy. In general, oral therapy is
      indicated for mild cases of secondary hyperparathyroidism (intact PTH<300 pg/mL)
      to maintain adequate level of serum PTH except "calcitriol oral pulse therapy"
      for moderate to severe cases. Recently, intravenous therapy has been introduced
      to treat more severe cases by using the advantage of rapid clearance of these
      metabolites. In order to use these preparations safely, adequate level of both
      serum intact PTH (150-300 pg/mL) and Ca/P product (<55) should be maintained to
      prevent from adynamic bone and vascular calcification.

PMID- 15577106
TI  - [Direct effects of vitamin D on bone].
AB  - Many investigators used to believe that active vitamin D is a promotive factor
      for bone resorption. However, active vitamin D shows an osteoprotective action
      when administrated as an anti-osteoporotic agent. Recently, active vitamin D
      agents are considered as an inhibitor for bone resorption. However, it is
      difficult to evaluate if it is also the case in chronic renal failure, since high
      turnovered osteopenia found in uremic patients are brought about by secondary
      hyperparathyroidism.

PMID- 15577107
TI  - [Prophylaxis and treatment of adynamic bone].
AB  - The pathogenesis of adynamic bone disease (ABD) attributes to calcium overload,
      active vitamin D (VD) metabolism, increase in inactive PTH (parathyroid hormone)
      fragments, or derangement of bone metabolism regulation factors. In particular,
      increased Ca overload plays a critical role in the development of ABD. Thus,
      alleviated Ca load by sevelamer hydrochloride and appropriate VD administration
      could be effective on not only prevention, and also treatment of ABD.

PMID- 15577108
TI  - [Osteomalacia and vitamin D deficiency in hemodialyzed patients].
AB  - Aluminum accumulation in plasma and tissues is a well-described complication
      among patients undergoing hemodialysis. Although the ratio of aluminum-induced
      osteomalacia has been decreasing year by year, there are still considerably many
      problems in such patients. Sources of aluminum now include food, drugs, and
      cooking tools. Besides, iron and strontium accumulations also induce
      osteomalacia. Early and accurate diagnosis of such metal toxicities is important
      because effective therapy is available.

PMID- 15577109
TI  - [Significance of point of no return in therapeutic strategy for treatment of
      renal osteodystrophy; from histopathological findings].
AB  - Point of no return implies a stage at irreversible to medical treatment of
      secondary hyperparathyroidism, clinically equivalent to intact PTH levels are
      more than 500 pg/mL in Japan. Most of glands resected by parathyroidectomy
      indicate nodular hyperplasia, increased parathyroid cell proliferation. Down
      regulation of calcium sensing receptors and vitamin D receptors in nodular
      parathyroid cells become a cause of resistance to medical treatment. Most of
      nodular glands are more than 500 mg in weight, predictable to existence at
      estimated volume and gland color signals by ultrasonographic method. New options
      both parathyroid injection therapy using ethanol and active vitamin D, and
      calcimimetic agent have a potential to change point of no return in therapeutic
      strategy for secondary hyperparathyroidism.

PMID- 15577110
TI  - [Significance of a new PTH assay (the comparison between whole-PTH and intact-PTH
      assay)].
AB  - It has been shown that intact-PTH assay measures not only full-length
      biologically active PTH with 84 amino acids, but also some PTH fragments such as
      (7-84) PTH. Whole-PTH assay is a new method believed to react only with (1-84)
      PTH. Because circulatory concentrations of various fragments of PTH are very high
      especially in patients with secondary hyperparathyroidism associated with renal
      failure, evaluation of PTH levels by whole-PTH assay seems to be useful for
      accurate assessment of parathyroid function in these patients.

PMID- 15577111
TI  - [The medical treatment strategy of secondary hyperparathyroidism use of vitamin D
      in Europe and America].
AB  - The medical treatment strategies of vitamin D appeared in the guideline of K/DOQI
      (Kidney Disease Outcomes Quality Initiative) in the U.S. and Clinical algorithms
      on renal osteodystrophy in Europe. The target intact PTH value is 150-300 pg/mL
      (16.5-33.0 pmol/L) in U.S. and 9-18 pmol/L (82-164 pg/mL ) in Europe. It was set
      up more highly in U.S. than in Europe. A European and American medical treatment
      strategies are not so different from that of Japan in the routes and metabolites
      of vitamin Ds.

PMID- 15577112
TI  - [Evolution in vitamin D treatment after debut of sevelamer hydrochloride in
      chronic renal failure patients].
AB  - Newly developed sevelamer hydrochlorid (Sev-HCl) has been recognized to show the
      effective control of the hyperphosphatemia in chronic renal failure patients,
      without elevation of serum Ca, Mg, and Al as well. Then, Sev-HCl has been
      expected to evolute the vitamin D treatment, and to reduce the ectopic
      calcifications through lowering Ca x P products. Although, relatively high
      frequent abdominal adverse effects in Sev-HCl treatment were reported, including
      life-threatening bowel occlusions or bowel perforations. It is important to use
      the appropriate dose of Sev-HCl avoiding the abdominal adverse effects.

PMID- 15577113
TI  - [Vitamin D and survival of hemodialysis patients].
AB  - Vitamin D receptors are expressed not only in the classical target organs (bone,
      parathyroid glands, kidneys and intestine) but also in other non-classical
      targets including arteries, heart, immune system, endocrine organs, and nervous
      system. Therefore, the deficiency of active forms of vitamin D in uremia may
      explain various abnormalities in biological functions and survival disadvantage
      in this disease condition. Previous studies reported that treatment with vitamin
      D had beneficial effects on cardiac and immune functions in dialysis patients. A
      recent observational cohort study indicated that the mortality risk was different
      between the groups taking different types of vitamin D analogues. We found that
      patients on a low-dose oral alfacalcidol showed a significantly lower risk for
      cardiovascular death than those without vitamin D supplementation. Although these
      observations need further confirmation by randomized controlled studies,
      appropriate use of active forms of vitamin D may improve the outcomes of patients
      with chronic kidney disease.

PMID- 15577114
TI  - [Advantage of intravenous pulse therapy with calcitriol or maxacalcitol in
      dialysis patients with renal hyperparathyroidism].
AB  - In dialysis patients, deficiency of calcitriol down regulates vitamin D receptor
      (VDR) and decreases density of Ca sensing receptor, resulting right shift of set
      point of extra cellular Ca concentrations to release of parathyroid hormone. And
      then, renal hyperparathyroidism occurs and progresses. The purpose of pulse
      therapy with calcitriol or its analogue is elevating extra cellular calcitriol
      level up to supra physiological level, which up regulates VDR and shift the set
      point to left. The extra cellular calcitriol level after injection of calcitriol
      cannot compare with the level after oral administration of calcitriol at the same
      dose. The left shift of set point is investigated 4 weeks after intravenous pulse
      therapy with calcitriol or maxacalcitol, and degree of shift to the left depends
      on the single dose of these medicines. There is another advantage of intravenous
      pulse therapy, which takes no account of drug compliance or existence of
      malabsorption of lipid soluble vitamins.

PMID- 15577115
TI  - [Vitamin D therapy in predialysis renal failure].
AB  - Vitamin D therapy is indicated in predialysis renal failure patients with
      secondary hyperparathyroidism caused by vitamin D deficiency. Vitamin D therapy
      brings about suppression of PTH and ameliorates oseitis fibrosa. To prevent
      aggravation of renal function, starting with small dose (0.25 microg/day) of
      calcitriol or alfacalcidol and dose adjustment of vitamin D with careful
      monitoring of serum calcium, phosphorus and PTH are recommended.

PMID- 15577116
TI  - [Serum calcium concentration and the safety of vitamin D therapy].
AB  - Vitamin D and its analogues are administered to patients with secondary
      hyperparathyroidism (SHPT) in chronic renal failure (CRF). Hypercalcemia is one
      of the complications of this therapy, and is thought to be not rare, though its
      frequency is not clearly documented. There is a need to monitor serum corrected
      (ionized) calcium concentration and parathyroid hormone (PTH) in order to
      administer vitamin D and its analogues safely. Intravenous administration of
      vitamin D provides advantages over oral administration, though no definite
      evidence could show which is better. Calcitriol and maxacalcitol are administered
      intravenously, and the latter is more likely to increase serum calcium
      concentration than the former. It must be very careful to administer vitamin D to
      patients with predialysis CRF because hypercalcemia can accelerate progression of
      renal dysfunction.

PMID- 15577117
TI  - [Optimum calcium concentration in the dialysate].
AB  - Ca dialysate composition should be tailored to each case. Many authors consider a
      dialysate Ca concentration of 3.0 mEq/L as the first choice for the majority of
      chronic hemodialysis patients. A dialysate Ca of 2.5 mEq/L may be used in
      patients with a high tendency to hypercalcemia. Calcimimetics therapy may well
      not have much implication for dialysate Ca concentration. The long-term safety of
      lower dialysate Ca concentration for treatment of adynamic bone disease should be
      carefully studied.

PMID- 15577118
TI  - [PEIT is the part of strategy for severe hyperparathyroidism in patients
      requiring hemodialysis].
AB  - Marked parathyroid hyperplasia is one of the characteristic features of severe
      hyperparathyroidism in patients requiring chronic hemodialysis. Most of these
      patients become resistant to conservative therapies such as calcitriol pulse
      therapy. For these patients, surgical removal of the enlarged parathyroid glands
      is usually necessary to control parathyroid hormone secretion. Recently,
      hyperparathyroidism in some of these patients have been managed by percutaneous
      ethanol injection therapy (PEIT) due to progress of imaging technology. In this
      study, we consider parathyroidectomy (PTx) and PEIT as a strategy of severe
      hyperparathyroidism patients. We conclude that PEIT, which is safe and effective
      therapy for 2HPT, makes possible to maintain long-term parathyroid function
      within the normal range. However 20% patients after PEIT need to convert
      PTx:parathyroidectomy after PEIT.

PMID- 15577119
TI  - [Parathyroidectomy for advanced renal hyperparathyroidim in hemodialysis].
AB  - Treatment of advanced secondary hyperparathyroidism should be shifted from to
      avoid progression of bone disease to protection of cardiovascular complications
      induced by ectopic calcification. Patients who suffer from advanced secondary
      hyperparathyroidism with uncontrollable hypercalcemia or/and hyperphosphatemia by
      medical treatment should be referred to surgical treatment at relatively early
      time. Total parathyroidectomy with forearm autograft is adequate operative
      procedure especially in patients who require long-term hemodialysis.

PMID- 15577120
TI  - Management of osteoporosis: the Indian perspective.
AB  - Osteoporosis is a common but neglected problem in India. The major challenges to
      management are lack of awareness and resource constraints. The management is also
      hampered by the non-availability of normative data for bone mineral density in
      Indians. Subclinical vitamin D deficiency is widespread. The drugs available in
      the country include calcium, vitamin D, hormone replacement therapy, raloxifene,
      alendronate, risedronate, calcitonin and teriparatide. Bisphosphonates
      (alendronate) constitute the mainstay of treatment in India. There is a need for
      evidence based, context specific and resource sensitive guidelines.

PMID- 15577121
TI  - Management of osteoporosis in Hong Kong.
AB  - Osteoporosis is among the top 3 medical conditions that are associated with
      greatest morbidity and reduction of quality of life of Hong Kong elderly
      subjects. The genetic and environmental risk factors for osteoporosis in southern
      Chinese as well as the current approach towards managing this growing health
      problem in Hong Kong are presented.

PMID- 15577122
TI  - Clinical management of osteoporosis in Singapore.
AB  - Osteoporosis is as common in Singapore as it is in Western countries and the
      incidence of hip fractures has risen five times among women in the last 30 years.
      Current treatment involves appropriate use of bone mineral density measurements
      and many medications are now available which can substantially reduce the risk of
      fractures. Increasing awareness of osteoporosis in the general population and
      keeping doctors updated about the latest trends in management are extremely
      important.

PMID- 15577123
TI  - Osteoporosis a disease for all; in Lebanon.
AB  - Osteoporosis is the most important metabolic disease leading to fracture and high
      mortality morbidity rates. With the increase of aging population, mainly in the
      developing work, it is estimated that the incidence of fracture will rise too.
      Osteoporosis known in the past to be a woman disease, it is now accepted that it
      affects man too. The risk factors for osteoporosis are known now, but one
      vertebral fracture, leading to more vertebral fractures and increasing the risk
      of hip fracture, stands by itself as an independent risk factor for osteoporosis
      even if BMD is normal or osteopenic. Vertebral fracture is associated with high
      mortality rate. At the same time it is work noting that osteoporosis in man is
      different than in women and finally we have now the means to diagnose correctly
      the disease, evaluate the fracture risk, treat and monitor the treatment. But
      incidence, fracture rate, peak bone mass in Lebanon are different than the
      European or North American one.

PMID- 15577124
TI  - Osteoporosis in Korea.
AB  - The increasing occurrence and high cost of osteoporosis pose an enormous public
      health problem. With continued aging of the populations, osteoporotic fractures
      may reach one of the major problem in Korea as well as in Asian countries.
      Although the prevalence of osteoporosis in Korea is somewhat not consistent
      because of different areas and machines measured bone mass, occurrence of hip
      fractures have increased about 4 folds during past 10 years. There is no
      satisfactory way to build up lost bone, thus, prevention is the best way which
      includes adequate intake of calcium, vitamin D, and protein, exercise, and stop
      smoking. As a second approach, pharmacologic therapy may be emphasized. Since
      most of pharmacologic agents for osteoporosis are available in Korea though their
      reimbursements are limited, preventive measures and pharmacologic therapies
      should be encouraged to attempt to reduce fragility fractures. Many doctors who
      work in the field of bone metabolism are establishing the new guidelines for
      osteoporosis and also attempt to revise the criteria for reimbursement nowadays.
      New paradigm for osteoporosis will be come and be utilized for clinical
      applications in the near future.

PMID- 15577125
TI  - Osteoporosis in Sri Lanka.
AB  - In Sri Lanka the median age, which was 25 in year 1991, is expected to rise to 45
      by the year 2041 and half of the population will be over 45 years and vulnerable
      to osteoporosis. We describe 2 large epidemiological studies done in Sri Lanka.
      The first one, Galle Prospective Osteoporosis Survey, in its initial phase
      recruited 350 women randomly from the current voters registers. 42.4% of women in
      the entire sample and 61.5% in women over 50 years were found to have
      osteoporosis. The second study was to assess the prevalence of stiffness index
      with heel ultrasound and calcium intake in a suburban population close to
      Colombo. We randomised 1250 from electoral register numbers and 986 people
      consented to participate. Stiffness index start decreasing after the age of 50,
      which is the average age of age of menopause. In men stiffness decreases after
      age of 70.

PMID- 15577126
TI  - Clinical management of osteoporosis in the Philippines.
AB  - Osteoporosis is considered a major health and economic problem. Exact figures in
      the Philippines may not be available at this time but there are clinical
      informations that will tell that osteoporosis is also a major concern in the
      country. Lack of knowledge about the existence of the disease is a major obstacle
      that is slowly being addressed. Although, osteoporosis is considered a major
      concern of postmenopausal women, low bone mass among premenopausal women has also
      been observed. Early diagnosis of the disease prior to occurrence of fracture is
      still the best approach physicians can do at this time and researches have
      provided good therapeutic options that can help us minimize the impact to the
      society of this what we call "silent epidemic".

PMID- 15577127
TI  - [Selective estrogen receptor modulators: mechanisms of action and their tissue
      selectivity].
AB  - The SERMs (Selective Estrogen Receptor Modulators) exert selective agonistic or
      antagonistic effects on various estrogen target tissues. Conformational change of
      SERM-bound Estrogen Receptor (ER) and tissue specific expression patterns of
      transcription co-factors have been well investigated as the underlying factors of
      tissue selectivity of the SERMs. Nongenomic action, modulation of protein levels
      of ER and co-factors, and activation of other nuclear receptors, have been also
      reported as mechanisms of tissue selectivity by SERMs.

PMID- 15577128
TI  - [SERM & bone metabolism: protective effects of SERM against fracture risk and its
      long-term beneficial effects].
AB  - The Multiple Outcomes of Raloxifene Evaluation (MORE) Trial enrolled 7,705 women
      with osteoporosis, defined by prevalent vertebral fractures and/or a bone mineral
      density (BMD) T score at -2.5 or below, who were treated with placebo or
      raloxifene at a dosage of 60 or 120 mg/day for 3 years. Raloxifene hydrochloride
      therapy significantly reduces the risk for vertebral fractures at 3 and 4 years
      administration group. The fact that Raloxifene administration causes the
      significant 25% reduction in overall risks in postmenopausal women indicate a
      favorable risk-benefit profile. These data suggested that raloxifene is effective
      to protect from the occurrence of bone fracture without causing increases of
      breast cancer and endometrial cancer, and improve overall health conditions in
      postmenopausal women.

PMID- 15577129
TI  - [Contribution of bone quality to fracture risk].
AB  - Recently Bone quality has been recognized as an important contributing factor of
      bone strength, as clearly stated in NIH (National Institute of Health) consensus
      development panel of 2000 that bone strength reflects both bone density and bone
      quality. Bone quality refers to architecture, turnover, damage accumulation,
      mineralization and matrix. In the treatment of osteoporosis anti-resorptive
      agents increase bone strength with decreasing bone turnover. It is important to
      control bone turnover within favorable range to increase bone strength without
      deterioration of bone quality.

PMID- 15577130
TI  - [Relationship between changes in biochemical markers of bone turnover and
      prediction value of fracture risk].
AB  - The change in BMD is poor predictor of vertebral fracture risk after Raloxifene
      treatment, whereas bone turnover markers were significantly associated with
      fracture risk. The percent change in osteocalcin (OC) was better able to predict
      the reduction in vertebral fracture risk than the percent change in femoral neck
      BMD in patients treated with Raloxifene in MORE study.

PMID- 15577131
TI  - [Additional effect of SERM: mammary gland].
AB  - One of selective estrogen receptor modulators (SERMs), tamoxifen, has been widely
      used for prevention of breast cancer, postoperative adjuvant therapy and
      treatment of advanced breast cancer. The relation of a long-term administration
      of tamoxifen and its adverse effects have been extensively investigated.
      Favorable effects of tamoxifen are:the reduction in the risk of contralateral
      breast cancer, gain in bone density in postmenopausal women and decrease in serum
      low-density lipoprotein cholesterol. Unfavorable effects are: gynecologic
      problems and the increase in the risk of endometrial cancer and thromboembolism.
      In contrast, another SERM, raloxifene, has reported to have similar favorable
      adverse effects but no unfavorable effect on endometrium.

PMID- 15577132
TI  - [Effects of raloxifene on other organs without bone: uterus].
AB  - Tamoxifen and Toremifene act as agonistic on uterine myometrium and endometrium.
      Tamoxifen leads re-enlargement of uterine myomas, recurrence of adenomyosis,
      atypical genital bleeding for endometrial hyperplasia and endometrial carcinoma
      in postmenopausal women. Therefore, it is necessary to evaluate the stage of
      pathological change on myometrium and endometrium, both before and during the
      period of administration of tamoxifen or toremifene. Unlike these drugs,
      raloxifene has an antagonistic action on uterine myometrium and endometrium. From
      these standpoints, we consider that raloxifene use lower the risks of uterine
      myomas, adenomyosis, endometrial hyperplasia and endometrial carcinoma.

PMID- 15577133
TI  - [Cardiovascular effects of SERM].
AB  - Raloxifene has an estrogenic effect on the cardio-vascular system. In vascular
      endothelium, both clinical and basic studies show that raloxifene induces the
      synthesis and release of nitric oxide. In vascular smooth muscle, basic study
      shows that raloxifene attenuates the PDGF-induced cell proliferation by both
      induction of apoptosis and arrest of the cell cycle. We now await the results of
      currently ongoing prospective large scale randomized control trial, Raloxifene
      Use of The Heart.

PMID- 15577134
TI  - [Additional effect of SERM: central nervous system].
AB  - Raloxifene is a selective estrogen-receptor modulator recently launched in Japan
      as a new medicine for treatment of postmenopausal osteoporosis. Raloxifene
      stimulates neurite outgrowth in cultured cells and increases hippocampal
      cholineacethyl trasferase activity and serotonin receptor in the brain of
      ovariectomized rats. As a part of the Multiple Outcomes of Raloxifene Evaluation
      trial, 7,478 postmenopausal women with osteoporosis were studied by using six
      tests of cognitive function. There was some evidence that Raloxifene may lower
      the risk of a decline in memory and attention. It is expected that novel SERM,
      which has more specific efficacy improving cognitive function will be developed.

PMID- 15577135
TI  - [Defining the role of raloxifene as a therapeutic agent for postmenopausal
      osteoporosis: focus on its pharmacological properties].
AB  - In this semiar, I propose to describe the pharmacological properties of
      raloxifene that provide a basis for its role in the treatment of postmenopausal
      osteoporosis. These pharmacological properties can be described as providing
      therapeutic benefits in the following three areas: 1) reduction in bone turnover,
      2) increases in bone mineral density, and 3) risk reduction in fractures. While
      reloxifene shares these effects with conventional bisphosphonates that are in
      common use for postmenopausal osteoporosis, it exerts its antiresorptive effects
      through a different mechanism of action from those of the bisphosphonates.
      Furthermore, raloxifene exerts its stimulatory or inhibitory effects on estrogen
      in a tissue-specific fashion as a selective estrogen-receptor-modulator (SERM),
      thereby providing a wide range of clinical benefits that result from its ability
      to exert estrogen-like beneficial effects in tissues other than bone while at the
      same time inhibiting estrogen-like deleterious effects in other tissues. I
      therefore propose to define the role of raloxifene as a viable therapeutic option
      in the treatment of postmenopausal osteoporosis in light of these unique
      pharmacological features. Current data suggests that raloxifene can be positioned
      somewhere in between hormone replacement therapy (HRT) and bisphosphonates, and
      is highly likely to be suitable for use in patients between the ages of 55 and
      70, while other agents may be indicated in special populations, such as
      premenopausal patients, postmenopausal patients with hot flushes, or elderly
      patients who may be placed at accelerated risk of developing femoral neck
      fractures. Thus, as a novel therapeutic option with unique clinical benefits, a
      far greater role may be expected for raloxifene in the treatment of
      postmenopausal osteoporosis than for other conventional therapeutic agents.

PMID- 15577136
TI  - [Effects of SERM on breast cancer and cardiovascular disease: making a comparison
      between raloxifene use and hormone replacement therapy on the risks of the
      diseases].
AB  - According to the report of MORE trial, raloxifene (RLX) compensate for the faults
      of hormone replacement therapy with the reasons following below; 1) RLX inhibits
      onset of breast cancer with estrogen receptor remarkably, 2) RLX inhibits onset
      of cardiovascular disease in its high risk group. However, because RLX has a
      elevated risk of venous thrombosis as same as hormone replacement therapy, we
      should give attention to this disease at the use of RLX.

PMID- 15577137
TI  - [Lasofoxifene, a next generation estrogen receptor modulator: preclinical
      studies].
AB  - Estrogen replacement therapy, in spite of efficacy in the prevention of
      osteoporotic fractures, has significant side effects and risks that limit its
      widespread usage in postmenopausal women. Thus significant medical need exists to
      find modalities that prevent osteoporosis, but without the side effects of
      estrogen. Selective estrogen receptor modulators (SERMs) have the potential to
      provide the skeletal benefits of estrogen without the increased risk of uterine
      and breast cancer. Tamoxifen, a first generation SERM is approved for the
      prevention and treatment of breast cancer, and raloxifene, a second generation
      SERM has been approved for the prevention and treatment of osteoporosis.
      Lasofoxifene, a new potent, nonsteroidal SERM, binds with high affinity to human
      estrogen receptors and acts as a tissue selective estrogen antagonist or agonist.
      In preclinical models of postmenopausal osteoporosis, lasofoxifene inhibited bone
      turnover and prevented bone loss throughout the skeleton. In studies designed to
      investigate the combination of lasofoxifene with estrogen, lasofoxifene blocked
      the hypertrophic effects of estrogen in the uterus, but did not block the bone
      protective effects. In immature and aged female rats, lasofoxifene did not affect
      the uterine weight and uterine histology. In preclinical studies designed to
      evaluate the effects of lasofoxifene on the uterus, a slight increase in wet
      uterine weight was observed in immature and aged female rats, but this difference
      was not observed in dry uterine weight suggesting that the increased uterine
      weight was due to increased water content in the tissue. In preclinical studies
      designed to evaluate the effects of lasofoxifene in breast cancer, lasofoxifene
      inhibited breast tumor formation in mice injected with human MCF-7 breast cancer
      cells and in rats bearing mammary carcinomas. Thus, in preclinical models,
      lasofoxifene, a next generation SERM, prevents estrogen deficiency-induced bone
      loss, inhibits breast tumor formation, and reduces serum cholesterol, without
      causing uterine hypertrophy. These data suggest that lasofoxifene is a new
      potential therapy for the prevention of osteoporosis in postmenopausal women.

PMID- 15577138
TI  - [SERM and quality of bone].
AB  - Now, we can prevent osteoporotic fractures by improvement of bone strength. It
      became clear that not only the increase of bone mineral density but also the
      improvement of bone quality are important factors for the mechanisms of
      preventing fractures. Measuring bone metabolism markers is contributing to
      evaluate bone quality. We presume SERM demonstrates a sustained fracture
      preventive effect through 4 yrs by normalizing the bone metabolism of
      postmenopausal women with osteoporosis.

PMID- 15577139
TI  - [Safety profile of raloxifene].
AB  - Selective estrogen receptor modulators (SERMs) are a diverse group of non
      steroidal (non hormonal) compounds developed to offer the postmenopausal women
      many of the advantages of estrogen therapy (ET) while avoiding undesired effects
      on reproductive and other tissues. Tamoxifen and toremifene, first generation
      SERMs are used for the adjuvant treatment of breast cancer worldwide, but their
      stimulatory effect on the uterus prevents their widespread use in other
      indications. A second generation SERM, raloxifene hydrochloride, a benzothiophene
      SERM is fully safe for the uterus and significantly reduces the risk of vertebral
      fractures in postmenopausal women with osteoporosis. The safety and efficacy of
      raloxifene in postmenopausal women have been studied extensively in more than
      40,000 women over 50 clinical trials in 30 countries. The majority of the trials
      have been large double-blind placebo-controlled trials, including Asia and Japan.
      Raloxifene is well tolerated, with the only common side effects significantly
      higher than placebo being hot flushes and minor leg cramps. Venous
      thromboembolism was the only adverse events of clinical significance but rare
      associated with raloxifene in Caucasian women, but was not observed so far in
      Asian countries.

PMID- 15577140
TI  - [Which is the better choice, estrogen or SERMs in postmenopausal women?].
AB  - Hormone replacement therapy (HRT) increases the bone mineral density (BMD) and
      reduces the risk of vertebral and hip fractures in postmenopausal women. But,
      long term HRT slightly increases the risk of breast cancer. Raloxifene is a
      selective estrogen receptor modulator that has estrogen agonist effects in the
      skeleton and cardiovascular system and estrogen antagonist effects in the uterus
      and breast. Raloxifene effectively prevents bone loss and significantly,
      increases lumbar spine, hip, and total body bone mineral density, raloxifene
      reduces the risk of vertebral fracture. Raloxifene treatment leads to no increase
      in vaginal bleeding or mastaigia and to greater than 70% reduction in risk for
      invasive breast cancer. But raloxifene increases the hot flashes in
      postmenopausal women. In conclusion, HRT is optimal therapy for prevention and
      treatment of osteoporosis in postmenopausal women with menopausal symptoms,
      raloxifene is optimal therapy for prevention and treatment of osteoporosis in
      postmenopausal women without menopausal symptoms.

PMID- 15577141
TI  - [Who are the candidates for the treatment by raloxifen ?].
AB  - There is evidence that raloxifene prevents vertebral fracture and it improves
      bone metabolism in patients with osteoporosis to the normal pre-menopausal level.
      Therefore, it is suitable to use for osteoporotic patients with adequate physical
      activity and those improvable by exercise. Patients who will be treated by
      anabolic agents are also good candidates for the treatment of raloxifene.

PMID- 15577142
TI  - [VDR function in skin].
AB  - Typical abnormalities of hereditary rickets type II patients were observed in the
      mice deficient of VDR with growth retardation, impaired bone formation and
      alopecia. Except alopecia, all of the abnormalities were rescued by dietary
      supplement of high minerals. Genetic mutations in the critical vitamin D
      biosynthesis enzyme in humans and mice also suffer rachtic phenotypes except
      alopecia. The function of VDR in skin will be discussed.

PMID- 15577143
TI  - [Vitamin D nuclear receptor and its signal transduction].
AB  - Vitamin D (VD) suppresses keratinocyte growth and induces its differentiation by
      binding to VD receptor. VD increases expression of phopholipase C and involucrin
      through VD response elements in the promoter. Vitamin D receptor (VDR) recruits
      mainly DRIP (vitamin D receptor interacting protein) during keratinocyte
      proliferation, but SRC (steroid receptor coactivator) during differentiation.

PMID- 15577144
TI  - [Vitamin D3 for external application--history of development and clinical
      application].
AB  - The study of vitamin D(3) topical applications has begun at Osaka University
      after Morimoto S. reported a patient with senile osteoporosis whose psoriasis was
      cured after treatment with 1-alpha-hydroxyvitamin D(3) [1 alpha (OH) D(3)].
      Another study of the first use of vitamin D(3) for psoriasis was reported in the
      same year in both Europe and the United States independently. Calcipotriol
      ointment came first onto the market for the treatment of psoriasis in Denmark in
      1990. In Japan, where tacalcitol ointment was first approved in 1993, six kinds
      of topical vitamin D(3) applications are now available. Now new applications of
      vitamin D(3) are anticipated to replace therapeutic drugs currently in use for
      psoriasis and other skin diseases.

PMID- 15577145
TI  - [Treatment of the keratinizing skin disorder, psoriasis, by topical vitamin D3].
AB  - The active vitamin D(3) regulates proliferation and differentiation of epidermal
      keratinocytes. Although topical application of steroid has been principal therapy
      for psoriasis, there occurs some side effects such as skin atropy,
      telangiectasis, and purpura. Recently topical vitamin D(3), tacalcitol,
      calcipotriol, and maxacalcitol, which avoid these side effects, are widely used
      for psoriasis. In this review, we discussed the mechanism, effect, and side
      effect of topical vitamin D(3) for psoriasis.

PMID- 15577146
TI  - [New perspective of vitamin D3 ointment--pruritic skin diseases: focused on
      prurigo].
AB  - It is generally accepted that topical steroid ointment and anti-histamine drug
      are the first choice of the treatment on pruritic skin diseases such as contact
      dermatitis, urticaria, prurigo, or pruritus cutanea. Among these diseases,
      prurigo is one of the most refractory skin disease to the common therapies. In
      this review, we would like to summarize the effect of vitamin D(3) to refractory
      skin disease on the basis of our clinical study.

PMID- 15577147
TI  - [New aspects on vitamin D3 ointment: vitamin D3 therapy for vitiligo].
AB  - Recently, there are some reports that combination therapy with topical vitamin
      D(3) ointment and PUVA (psonalen ultraviolet A) or vitamin D(3) alone improved
      vitiligo. We conducted an open trial on 27 patients, most of whom had poor
      clinical responses to the prior therapies, topical steroid ointment and PUVA. The
      clinical effect revealed that 13 of 27 patients showed more than 30% improvement.
      Combination therapy with topical vitamin D(3) ointment and linear polarrised
      infrared, UVA, solar irradiation, can be used as an alternative therapy for
      vitiligo vulgaris.

PMID- 15577148
TI  - [New aspects on vitamin D3 ointment; treatment of senile warts with topical
      application of active forms of vitamin D3].
AB  - Vitamin D(3) ointment is widely used for the therapy of inflammatory keratotic
      dermatoses such as psoriasis. Senile wart (seborrheic keratosis) is a benign
      tumor, which occurs mainly in the elderly. It has been treated with surgical
      procedures, freezing with liquid nitrogen, or laser therapy. We tried to treat
      senile wart with active forms of topical vitamin D(3) (tacalcitol, calcipotriol
      or maxacalcitol). These topical vitamin D(3) ointments were applied on senile
      warts once or twice a day. Out of 116 cases those were treated for more than
      three months, 35 cases (30.2%) showed excellent response that means more than 80%
      of decreasing of tumor volume, 54 cases (46.6%) showed moderate response that
      means 40 to 80% of decreasing, 27 cases (23.2%) showed no remarkable changes or
      decreasing less than 40%. The tumor disappeared without any inflammatory change
      such as erythema or swelling. Any of side effects were not observed on all
      patients whose senile warts were treated with topical vitamin D(3).

PMID- 15577149
TI  - [Measures for osteoporosis in the dermatological field--vitamin D3 and
      bisphosphonate].
AB  - Steroid-induced osteoporosis is the most common form of osteoporosis in the
      dermatological diseases, but there have been only few data concerning the
      treatment based on clinical evidences. For management of osteoporosis, the
      efficacy of vitamin D(3) and bisphosphonate had been demonstrated by meta
      analytic approach. Ten dermatological patients in our clinic who had received
      long-term oral steroids and showed bone loss were treated with 5 mg/day of
      alendronate for one year, and showed significant increase in the bone mineral
      density of the lumbar spine. In dermatological patients requiring long-term
      systemic steroids, administration of drugs such as vitamin D(3) or bisphosphonate
      should be started earlier.

PMID- 15577150
TI  - [Case Report No.143: one case of multiple endosecretory-adenomatosis accompanied
      with ventricula ependymoma].

PMID- 15577151
TI  - [Present condition and future direction of osteoporosis in Japan].
AB  - The purpose of this special issue is to clarify the problems in the prevention,
      the treatment and the care of osteoporotic patients in Japan. Herein, we
      presented the accumulating evidence about the epidemiology, the prevention, the
      screening and the therapy of osteoporosis. We also introduced the countermeasures
      for osteoporosis through the life and the medical financial studies etc. The
      government, the medical societies and the foundations support the studies for
      osteoporosis and have proposed the guidelines for osteoporosis. We overviewed the
      prospective of osteoporosis and fracture prevention. For the establishment of
      healthy longevity society, we should continue the effort to solve the problems in
      osteoporosis in Japan.

PMID- 15577152
TI  - [Epidemiology of osteoporosis and fracture].
AB  - Prevalence of osteoporosis is increasing with age. And it reached about 50% for
      women in their late seventies and about 20% for men of the same age. In Japan,
      osteoporosis population is estimated at over ten million people. Spine fracture
      is very common in the elderly, with a lifetime risk of 37% for Japanese women
      aged 50. Incidence of spine fracture increased at relatively early stages of old
      age. Hip fracture rapidly increases among those at ages over 70, with a lifetime
      risk of about 14% for women aged 50 and 10-year fracture probability of 3% and
      10% for women aged 70 and those aged 80, respectively.

PMID- 15577153
TI  - [Consequences of osteoporotic fractures--epidemiological review].
AB  - Most fractures among the elderly is a common consequence of osteoporosis and
      occurs very frequently in older people. Osteoporotic fractures are associated
      with diminished physical and functional performance, difficulties in performing
      activities of daily living (ADL), and a decline in several aspects of well-being
      or quality of life (QOL). In this article, consequence of osteoporotic fractures
      are reviewed based on the recent population-based epidemiological studies.

PMID- 15577154
TI  - [Bone mass and lifestyle-effect of exercise and nutrition].
AB  - This article discussed the effect of exercise and/or nutrition on bone mineral
      density (BMD), and the quality and quantity of exercise and nutrition for the
      primary prevention of osteoporosis. The evidence suggested that exercise and
      nutritional supplements are effective for increasing BMD among children or to
      inhibit the loss of BMD after menopause. However, the evidence to discuss the
      effective kind and amount of exercise is limited. In addition, more evidence is
      needed about increasing the nutritional intake from food and combination with
      nutritional supplements. After the intervention, the effects of exercise and
      nutrition were lost. Thus lifestyle modification should be easy to accept and
      continue.

PMID- 15577155
TI  - [Cost-effectiveness of osteoporosis treatment].
AB  - With Japan's rapidly aging population, a remarkable increase in fragility
      fractures due to osteoporosis and exhaustion of medical care resources is
      anticipated. Therefore, the cost-effectiveness of osteoporosis treatment will be
      more important than ever before. Because the outcome is estimated in terms of
      gain of life time and improvement in quality of living, a treatment is judged to
      be cost-effective when its cost per quality adjusted life year (QYALY) gained is
      below an acceptable threshold. According to studies in Western countries,
      medicines in use today including alendronate, risedronate, calcium plus vitamin
      D, calcitonin and raloxifene are cost-effective. However, studies on the cost
      effectiveness of osteoporosis treatment based on Japanese data are thought to be
      needed for Japanese patients.

PMID- 15577156
TI  - [Diagnosis and medical checkup of osteoporosis].
AB  - In this article, the diagnosis and medical checkup of osteoporosis are reviewed.
      Osteoporosis is defined by bone histomorphometry, radiography, morphometry of
      vertebral body, and semiquantitative assessment of vertebral deformity.
      Diagnostic criteria of osteoporosis in Japanese Society for Bone and Mineral
      Research is composed of fragility fracture and low bone mass. The aim of
      osteoporosis checkup is to detect subjects with low bone mass using measurement
      of bone mineral density.

PMID- 15577157
TI  - [Prevention of osteoporosis in childhood and adolescence].
AB  - Osteoporosis prevention starts in childhood and adolescence. These periods are
      important to achieve adult peak bone mass and establish health behaviors. Health
      behaviors influence the development of osteoporosis later in life, so we should
      aim osteoporosis prevention efforts toward children and adolescents by
      encouraging habits that promote bone growth and development.

PMID- 15577158
TI  - [Strategies for the prevention of osteoporosis in young and middle aged adults].
AB  - Strategies for the prevention of osteoporosis in young and middle aged adults
      include: a balanced diet which provides a calcium intake of at least 800 mg/day;
      encouragement of a physically active lifestyle; avoidance of smoking and of high
      alcohol and caffeine intakes; minimization of glucocorticoid use; promotion of
      intake of vitamin D, protein, vitamin K, vitamin C and potassium.

PMID- 15577159
TI  - [Lifestyle management approaches in postmenopausal osteoporosis].
AB  - Of the lifestyle management approaches to postmenopausal osteoporosis
      recommended, encouraging walking appears to be more relevant than ensuring
      appropriate nutritional intake in preventing bone loss. The focus of the current
      lecture is therefore on encouraging exercise, as it is not hard to imagine the
      physical impact of exercise on bone mineral density. As has long been pointed
      out, in fact, the initial management of postmenopausal osteoporosis consists in
      subjecting the bone to a continual physical stress, including exercise. In this
      regard, aerobic exercise including walking has been widely recommended;however,
      there is no clear evidence showing aerobic exercise to be superior to other kinds
      of exercise, while several studies reported on the benefit of combining aerobic
      exercise with pharmacological treatments in postmenopausal women, including our
      own series. Physical exercise programs or guidelines aimed at the prophylaxis of
      postmenopausal osteoporosis that draw on research evidence supporting the benefit
      of encouraging physical exercise need yet to be put in place as a matter of
      urgency.

PMID- 15577160
TI  - [The management of osteoporosis in the elderly].
AB  - In the elderly, the clinical features of osteoporosis are characterized by the
      variety among patients. For the purpose of the fracture prevention, it is
      important that the managements are suitable for the personal pathophysiological
      status, and coordinated by both the treatment of osteoporosis and the reduction
      of fall risks. In addition, the management plan should be immediately modified
      when the difficulties are observed.

PMID- 15577161
TI  - [Osteoporosis prevention in the reform of the long-term care insurance system].
AB  - The reform of the long-term care insurance system is being discussed at the
      Ministry of the Health, Labor and Welfare in Japan. The key issue in the process
      is to transform the system into prevention-oriented one. Prevention of
      osteoporosis will play major role in it.

PMID- 15577162
TI  - [Prevention of fall and fracture].
AB  - Many programs to prevent falls were designed for intervention in fall risk
      factors. Several meta-analyses, based on many randomized, controlled trials and
      conducted for the purpose of evaluating the efficacy of these interventions, have
      been published recently. According to these studies, multifactorial fall risk
      assessment and management, as well as muscle strengthening and balance
      retraining, succeeded in reducing falls by approximately 10-38%. Only New Zealand
      trials were found to decrease even injurious falls, with reduction of moderate or
      serious injuries by 35% using fall prevention. However, there was no significant
      difference between the two groups when looking at only serious injuries such as
      fractures. Thus, fall prevention can prevent falls, but not fractures at present.

PMID- 15577163
TI  - [Pharmacological therapy of osteoporosis].
AB  - The aim of pharmacological therapy for osteoporosis is to prevent osteoporotic
      fractures. Low bone mineral density, previous fractures, high values of bone
      turnover markers, and age are the independent risk factors for osteoporotic
      vertebral fractures. These clinical parameters should be utilized to start and
      choose the drugs for osteoporosis.

PMID- 15577164
TI  - [Right or wrong of the hormone replacement therapy involving osteoporosis].
AB  - Hormone Replacement Therapy (HRT) is replacement of depleted endogenous estrogen
      for postmenopausal women. Usually progestin is used in combination to avoid
      endometrial proliferation. As for bone metabolism, estrogens exert bone
      protective effect through inhibition of bone absorption. HRT has been shown to
      improve bone mineral density and to lower the risk of osteoporotic bone fracture.
      However, recent clinical studies proved that HRT not only raise the risk of
      breast cancer, but also increase the incidence of atherosclerotic cardiovascular
      diseases. Other than the treatment of postmenopausal vasomotor symptoms, the
      benefit of HRT is thought to be hard to outweigh its risk. To resolve this
      problem, low dose HRT and SERM (Selective Estrogen Receptor Modulator) regimens
      are under investigation. The evidences of androgen replacement for aged men are
      not accumulated enough to verify its effects and long term safety.

PMID- 15577165
TI  - [Vertebroplasty].
AB  - Vertebroplasty for pseudoartrosis of vertebral fracture using PMMA
      (polymethylmetacrylate) or CPC (calcium phosphate cement) is a new less invasive
      surgical method providing sufficient pain relief and correction of kyphosis.

PMID- 15577166
TI  - [Calcium intake and osteoporosis].
AB  - It has been well known that calcium (Ca) deficiency is a major risk factor for
      osteoporosis. However, few reliable evidences were available regarding the
      beneficial effect of increased dietary Ca in osteoporosis. Meta-analysis of the
      recently reported randomized clinical trials revealed that the beneficial effect
      of increased dietary Ca on BMD and/or fracture prevention was very small, if any.

PMID- 15577167
TI  - [Serial 1 Development of jaws; over view--development of jaws in vertebrates].
AB  - Mouth is entrance to the alimentary canal of the animal. One of the most
      significant evolutionary advances made in the evolution of vertebrate was the
      development of jaws. The presence of jaws manipulated by muscles allows an
      organism to grasp feed firmly. From primitive amphibian to primitive reptile,
      there had only primary oral cavity, but an advanced mammal-like reptile was
      divided primary oral cavity between oral and nasal cavity. An advanced mammal
      like reptile was able to maintain breathing easily while the mouth is functioning
      in eating, fore get the development of a secondary palate. In the development of
      vertebrate it made many characteristic forms of jaws. In this series we will
      discuss that development and morphological character of the jaws.

PMID- 15577168
TI  - [Bone mineral density measurements for diagnosis of osteoporosis and the risk
      assessment].
AB  - Osteoporosis is a major public health problem. So bone mineral density (BMD) is
      highly correlated with bone strength, accounting for 60-80% of the variance in
      ultimate strength of bone tissue, BMD measurement has important role in diagnosis
      of osteoporosis, screening, and clinical decision-making for treatment. In this
      article, conventional theory and new theory about cut-off point and fracture risk
      were reviewed.

PMID- 15577169
TI  - [Evaluation of osteoporosis treatment efficacy by bone mass measurement].
AB  - Dual energy X-ray absorptiometry contributes to the effective treatment of
      osteoporosis, although several conditions are required, such as use of effective
      drugs for bone mass, non-deformed lumbar spines, and enough periods before
      evaluation of the efficacy. Recent clinical works suggest amelioration of bone
      quality is more important than the bone mass increase for fracture prevention.
      But, measurement of bone mass is still essential for the evaluation of
      osteoporosis treatment under the circumstance that no modalities for bone quality
      are available clinically.

PMID- 15577170
TI  - [Assessment of bone quality--present and future].
AB  - Bone quality including "structural property" and "material property" , which is
      strongly affected by bone remodeling and has an influence on bone biomechanical
      property. Structural property means macroscopical geometry, bone size, trabecular
      microstructure, cortical thickness and cortical porosity. Material property means
      mineralization, crystal size, collagen and microdamage. Although most of them are
      analyzed in vitro, in the future, noninvasive assessment of bone quality may help
      to guide therapy of osteoporosis.

PMID- 15577171
TI  - [Dual-energy X-ray absorptiometry in clinical practice and its trouble spots in
      bone mineral measurement].
AB  - The technique of dual energy X-ray absorptiometry (DXA) is widely used for bone
      mineral density (BMD) measurement at present. BMD at PA spine should be measured
      for diagnosis of osteoporosis in all patients. If BMD at PA spine is
      inappropriate for the evaluation, proximal femur is selected for the measurement
      site. Various clinical issues pertained to this technique have been known. This
      paper reviewed clinical practice and trouble spots of BMD measurements at AP
      spine, proximal femur, and distal forearm.

PMID- 15577172
TI  - [Progress in quantitative ultrasound in measurement of bone quality].
AB  - The use of QUS (quantitative ultrasound) for the assessment of skeletal status
      has been continued and accelerating interest in recent years. The attractive of
      QUS lies in its low cost, portability, and freedom from ionizing radiation. These
      benefits, combined with clinical results showing good diagnostic sensitivity and
      the ability to predict fracture risk, have encouraged further basic
      investigation.

PMID- 15577173
TI  - [Micro MRI of trabecular bone].
AB  - Recent progress in noninvasive imaging techniques--notably magnetic resonance
      imaging (MRI) and computed tomography (CT)--in terms of improvements in
      achievable signal-to-noise ratio (SNR) and spatial resolution, has led to
      specialized modalities (often referred to micro-CT and micro-MRI) that now enable
      visualization and quantitative analysis of trabecular bone architecture in vivo
      in animals and humans. We have during the past decade been dedicated to the
      development of acquisition and processing methods permitting quantitative
      characterization of the complex architecture of trabecular and cortical bone from
      micro-MRI data obtained in the limited spatial resolution regime inherent to
      measurements performed in vivo. Fundamental to achieving such a goal is an image
      acquisition strategy that ensures faithful retrieval of the structural features,
      which includes appropriate imaging pulse sequences and control of and correction
      for involuntary subject motion. Preprocessing of the raw images results in noise
      free grayscale images representing maps of bone volume fraction, which are
      subvoxel-processed (a method for reducing partial volume blurring with
      application) to yield images in higher spatial resolution. From the binarized and
      skeletonized images the three-dimensional topology of the network can be
      retrieved allowing each voxel to be characterized as belonging to a surface,
      curve or junction between the fundamental topological types. Surfaces and curves
      are the lower-dimensionality counterparts of plates and rods for better
      differentiation of bone quality.

PMID- 15577174
TI  - [Bone mass measurement in pediatrics].
AB  - The methodology of the bone mineral measurement from childhood through
      adolescence contains a few problems. Continuously growing child shows continuous
      enlargement of the bone and the difference in bone size exerts ineligible effects
      on the DXA value. Therefore, we should be careful to evaluate the value from the
      point of this view. This manuscript overviewed normal bone growth and problems in
      bone mineral assessment during childhood and adolescence.

PMID- 15577175
TI  - [Effectiveness of measuring bone mineral density in preventing osteoporosis].
AB  - A self-administrated questionnaire was performed to clarify the actual
      circumstances of community-based screening for osteoporosis. The results revealed
      that only 25 percent of communities performed follow-up of high-risk
      participants, representing a disappointing result for assessing evidence of the
      benefits of measuring bone mineral density in preventing osteoporosis. Secondly,
      a review of the literature was performed to clarify the benefits of measuring
      bone mineral density in preventing osteoporosis. The review revealed that
      increased measurements could predict fractures among elderly and peri- and
      postmenopausal women, and elderly men.

PMID- 15577176
TI  - [Compact MRI].
AB  - The compact MRI for bone density measurements is a small-size MRI specially
      designed for the calcaneus by using a small permanent magnet. This system can
      measure a trabecular bone volume fraction (TBVF) for a clearly defined 3D region.
      The correlation coefficient (R(2)) between TBVF and QUS-SOS, and that between
      TBVF and DXA were about 0.29 for about 100 female subjects, and about 0.38 for
      about 20 subjects, respectively. This system will be especially useful for bone
      density measurements for children and young people.

PMID- 15577177
TI  - [Ultrasonic wave propagation characteristics of cancellous bone].
AB  - Ultrasonic measurements of bone status or bone mass density are generally
      performed using ultrasonic parameters consisting of the slope of frequency
      dependent attenuation (or broadband ultrasound attenuation: BUA) and the speed of
      sound (SOS). Many results of in vitro laboratory measurements and in vivo
      clinical trials have shown the ultrasonic parameters, BUA and SOS correlate
      significantly with the bone mass density measured by X-ray method. However, there
      exists some problem inherent in the ultrasonic method on the reproducibility and
      the uncertainty of measured ultrasonic parameters. The ultrasonic properties of
      cancellous bone have been experimentally and theoretically studied by author's
      group to reveal problems inherent in the ultrasonic method. According to
      experimental and theoretical studies, two longitudinal waves, fast wave and slow
      wave are clearly observed. The propagation speed of the fast wave increases with
      the bone density and that of the slow wave decreases very slightly with the bone
      density. Whereas the attenuation constant of the fast wave is much higher than
      that of the slow wave and is almost independent of the bone density, but in
      contrast, the attenuation constant of the slow wave increases considerably with
      the bone density. Experimental results on transmitted ultrasonic wave through
      cancellous bone show that the amplitude of the slow wave decreases with the bone
      density and the amplitude of the fast wave, on the contrary, increases with the
      bone density. This dependence of the fast wave amplitude on the bone density can
      not be explained by the attenuation constant. The ultrasonic wave propagation
      path through cancellous bone is modelized to clarify the propagation phenomenon
      and to specify the causality between ultrasonic wave parameters and the bone
      density. The bone density is quantitatively formulated based on the modelization
      as a function of the amplitude and the propagation speed of the fast wave.

PMID- 15577178
TI  - [Glucocorticoid-induced osteoporosis and bone mineral densimetry].
AB  - While the diagnosis and management of primary osteoporosis have been established
      and widely utilized, these for glucocorticoid-induced osteoporosis (GIOP), i.e. a
      representative of secondary osteoporosis, are on their way. GIOP caused fractures
      at a higher bone mineral density (BMD) compared to primary osteoporosis. The cut
      off value of the BMD for prediction of fractures was around 80% of the young
      adult means (T-score; -1.5). As this value would give a useful diagnostic point
      for initiating treatments, measurements of BMD should be a significant tool for
      management of GIOP.

PMID- 15577179
TI  - [Therapy for ROD and measurement of the bone mass].
AB  - The kidney deeply takes part in phosphorus and vitamin D metabolism. The chronic
      kidney disease patients usually suffer from serious bone disease. They are
      prescribed the glucocorticoid medication for primary kidney disease, as nephrotic
      syndrome and collagen renal disease, with aging. The end of therapeutic target is
      normal bone structure with normal bone turnover in CKD patients. The control of
      serum Ca and phosphorus level is important step and also another target. This
      issue describes the problem and the advancement of treatment and the measurement
      of the bone mass from this viewpoint.

PMID- 15577180
TI  - [Anabolic effects of statin and beta-blocker on bone metabolism].
AB  - Recent studies suggest that statins and beta-blockers which are widely prescribed
      for the treatment of hyperlipidemia and hypertension play an important role in
      bone metabolism. Statins inhibit HMG-CoA reductase and its down-stream mevalonate
      pathway. They modulate osteoclastic and osteoblastic activity, since metabolites
      of mevalonate are critically involved in bone cell biology. Sympathetic nervous
      system also controls bone formation via its direct effects on osteoblasts.
      Administration of beta-blockers may lead to an increase bone mass and reduce the
      risk of fracture. Statins and beta-blockers could have anabolic effects on bone
      metabolism and may be potential therapeutic implications for osteoporosis.

PMID- 15577181
TI  - [Osteoporosis and mineral intake].
AB  - For prevention against the development of osteoporosis and related fractures, the
      importance of sufficient intake of calcium and vitamin D has been increasingly
      recognized. However, due to increasing intake of calcium, the relative intake of
      magnesium and trace elements, such as zinc and copper has been relatively
      decreasing and thus been focused in recent years. On this article, we will give
      an outline of the importance of magnesium and trace elements in the regulation of
      bone metabolism.

PMID- 15577183
TI  - Anthocyanins-More Than Nature's Colours.

PMID- 15577182
TI  - [Phylogeny of the jaw].
AB  - Since primary life appeared in the sea about 3.8 billion years ago, the Agnatha
      improved a part of the respiratory organ, or brachial arch into the jaw during
      the evolutionary process. The resulting Gnathostomata could catch bigger fish by
      using the strong jaw. In addition, they developed specific sensory organs in the
      head, including nose, eyes and ears for detecting position of diets, brain for
      treating the sensory information, and muscles for masticating foods. Such
      development of jaw from the brachial arch had an important meaning in the
      evolutional history of organisms.

PMID- 15577184
TI  - LC/PDA/ESI-MS Profiling and Radical Scavenging Activity of Anthocyanins in
      Various Berries.
AB  - Anthocyanin extracts of two blueberries, Vaccinium myrtillus (bilberry) and
      Vaccinium ashei (rabbiteye blueberry), and of three other berries, Ribes nigrum
      (black currant), Aronia melanocarpa (chokeberry), and Sambucus nigra
      (elderberry), were analyzed by high-performance liquid chromatography coupled
      with photodiode array detection and electrospray ionization - mass spectrometry
      (LC/PDA/ESI-MS). Both bilberry and rabbiteye blueberry contained 15 identical
      anthocyanins with different distribution patterns. Black currant, chokeberry, and
      elderberry contained 6, 4, and 4 kinds of anthocyanins, respectively. The radical
      scavenging activities of these berry extracts were analyzed by using 2,2-diphenyl
      1-picrylhydrazyl (DPPH). All these extracts showed potent antiradical activities.

PMID- 15577185
TI  - The Change of Total Anthocyanins in Blueberries and Their Antioxidant Effect
      After Drying and Freezing.
AB  - This study examined the effects of freezing, storage, and cabinet drying on the
      anthocyanin content and antioxidant activity of blueberries (Vaccinium corymbosum
      L). Fresh samples were stored for two weeks at $?5^?circ$ C while frozen samples
      were kept for up to three months at $-20^?circ$ C. There were two drying
      treatments, one including osmotic pretreatment followed by cabinet drying and the
      other involving only cabinet drying. Total anthocyanins found in fresh
      blueberries were $7.2 ?pm 0.5$ mg/g dry matter, expressed as cyanidin 3
      rutinoside equivalents. In comparison with fresh samples, total anthocyanins in
      untreated and pretreated dried blueberries were significantly reduced to $4.3 ?pm
      0.1$ mg/g solid content, 41% loss, and $3.7 ?pm 0.2$ mg/g solid content, 49%
      loss, respectively. Osmotic treatment followed by a thermal treatment had a
      greater effect on anthocyanin loss than the thermal treatment alone. In contrast,
      the frozen samples did not show any significant decrease in anthocyanin level
      during three months of storage. Measurement of the antioxidant activity of
      anthocyanin extracts from blueberries showed there was no significant difference
      between fresh, dried, and frozen blueberries.

PMID- 15577186
TI  - Sour Cherry (Prunus cerasus L) Anthocyanins as Ingredients for Functional Foods.
AB  - In the recent years many studies on anthocyanins have revealed their strong
      antioxidant activity and their possible use as chemotherapeutics. The finding
      that sour cherries (Prunus cerasus L) (also called tart cherries) contain high
      levels of anthocyanins that possess strong antioxidant and anti-inflammatory
      properties has attracted much attention to this species. Here we report the
      preliminary results of the induction of anthocyanin biosynthesis in sour cherry
      callus cell cultures. The evaluation and characterization of the in vitro
      produced pigments are compared to those of the anthocyanins found in vivo in
      fruits of several sour cherry cultivars. Interestingly, the anthocyanin profiles
      found in whole fruit extracts were similar in all tested genotypes but were
      different with respect to the callus extract. The evaluation of antioxidant
      activity, performed by ORAC and TEAC assays, revealed a relatively high
      antioxidant capacity for the fruit extracts (from 1145 to 2592 $?mu $ mol TE/100
      g FW) and a lower one for the callus extract (688 $?mu $ mol TE/100 g FW).

PMID- 15577187
TI  - Effect of Light on Anthocyanin Levels in Submerged, Harvested Cranberry Fruit.
AB  - Anthocyanins are a group of plant antioxidants known for their therapeutic use.
      The effects of natural light, red light, and far-red light on individual as well
      as total anthocyanin content in cranberry fruit (Vaccinium macrocarpon Ait) were
      examined in an experimental setting designed to mimic water-harvesting
      conditions. The reversed-phase high performance liquid chromatography (HPLC)
      method was used to separate and analyze the anthocyanins. In contrast to the case
      of the control sample that was kept in the dark, natural light increased the
      total anthocyanin level by $75.3$ % and $87.2$ % after 24 and 48 hours water
      immersion, respectively. Red light and far-red light increased the total
      anthocyanin level by $41.5$ % and $34.7$ %, respectively. The amount of each
      individual anthocyanin increased differently under natural light, red light, and
      far-red light, suggesting that expressions of enzymes that catalyze the
      anthocyanin biosynthesis are regulated differently by environments.

PMID- 15577188
TI  - To Stretch the Boundary of Secondary Metabolite Production in Plant Cell-Based
      Bioprocessing: Anthocyanin as a Case Study.
AB  - Plant cells and tissue cultures hold great promise for controlled production of a
      myriad of useful secondary metabolites on demand. The current yield and
      productivity cannot fulfill the commercial goal of a plant cell-based bioprocess
      for the production of most secondary metabolites. In order to stretch the
      boundary, recent advances, new directions and opportunities in plant cell-based
      bioprocessing, have been critically examined for the 10 years from 1992 to 2002.
      A review of the literature indicated that most of the R&D work was devoted
      predominantly to studies at an empirical level. A rational approach to molecular
      plant cell bioprocessing based on the fundamental understanding of metabolic
      pathways and their regulations is urgently required to stimulate further
      advances; however, the strategies and technical framework are still being
      developed. It is the aim of this review to take a step forward in framing
      workable strategies and technologies for molecular plant cell-based
      bioprocessing. Using anthocyanin biosynthesis as a case study, an integrated
      postgenomic approach has been proposed. This combines the functional analysis of
      metabolic pathways for biosynthesis of a particular metabolite from profiling of
      gene expression and protein expression to metabolic profiling. A global
      correlation not only can thus be established at the three molecular levels, but
      also places emphasis on the interactions between primary metabolism and secondary
      metabolism; between competing and/or complimentary pathways; and between
      biosynthetic and post-biosynthetic events.

PMID- 15577189
TI  - Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial
      Parameters in High-Risk Subjects.
AB  - Grape seed extract (GSE) has in vitro antioxidant activity but whether or not it
      works in vivo is not clear. In a fully randomised, crossover trial with 4-week
      treatment periods on 36 men and women with above-average vascular risk, we aimed
      to demonstrate that 2 g/day of GSE (1 g of polyphenols) alone, or with 1 g/day of
      added quercetin in yoghurt, favourably alters vascular function, endothelial
      function, and degree of oxidative damage in comparison to a control yoghurt. GSE
      alone improved flow-mediated dilatation determined ultrasonically by an absolute
      $1.1$ % compared with control. There was no effect of the combination of GSE with
      quercetin. No other blood or urine measure was altered. Thus sufficient
      polyphenols from GSE appear to be absorbed to influence endothelial nitric oxide
      production, and GSE has the potential to favourably influence vascular function.

PMID- 15577190
TI  - Characterization of Acylated Anthocyanins in Callus Induced From Storage Root of
      Purple-Fleshed Sweet Potato, Ipomoea batatas L.
AB  - Four anthocyanins were isolated from a highly pigmented callus induced from the
      storage root of purple-fleshed sweet potato (Ipomoea batatas L) cultivar
      Ayamurasaki. The anthocyanins were respectively identified as cyanidin 3- $O$ -(2
      $O$ -(6- $O$ -( $E$ )-caffeoyl- $?beta$ -D-glucopyranosyl)- $?beta$ -D
      glucopyranoside)-5- $O$ - $?beta$ -D-glucopyranoside, cyanidin 3- $O$ -(2- $O$ 
      (6- $O$ -( $E$ )- $p$ -coumaroyl- $?beta$ -D-glucopyranosyl)-6- $O$ -( $E$ )
      caffeoyl- $?beta$ -D-glucopyranoside)-5- $O$ - $?beta$ -D-glucopyranoside,
      cyanidin 3- $O$ -(2- $O$ -(6- $O$ -( $E$ )- $p$ -coumaroyl- $?beta$ -D
      glucopyranosyl)-6- $O$ -( $E$ )- $p$ -coumaroyl- $?beta$ -D-glucopyranoside)-5-
      $O$ - $?beta$ -D-glucopyranoside, and peonidin 3- $O$ -(2- $O$ -(6- $O$ -( $E$ )-
      $p$ -coumaroyl- $?beta$ -D-glucopyranosyl)-6- $O$ -( $E$ )- $p$ -coumaroyl-
      $?beta$ -D-glucopyranoside)-5- $O$ - $?beta$ -D-glucopyranoside by chemical and
      spectroscopic analyses. These anthocyanins were examined with respect to the
      stability in neutral aqueous solution as well as the radical scavenging activity
      against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These acylated
      anthocyanins exhibited both higher stability and higher DPPH radical scavenging
      activity than corresponding nonacylated cyanidin and peonidin 3- $O$ -sophoroside
      5- $O$ -glucosides.

PMID- 15577191
TI  - Caffeoylquinic Acids Generated In Vitro in a High-Anthocyanin-Accumulating Sweet
      potato Cell Line.
AB  - Accumulation of phenolic compounds has been monitored in a suspension culture of
      anthocyanin-accumulating sweet potato cell line grown under the conditions of
      modified Murashige and Skoog high-anthocyanin production medium (APM) over a
      period of 24 days. Tissue samples extracted with 15% acetic acid were analysed
      using HPLC at a detection wavelength of 326 nm. Among others, the following
      derivatives of caffeoylquinic acids were detected: 4,5-dicaffeoylquinic acid, 3,5
      dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 3,4,5-tricaffeoylquinic
      acid. Their total amount reached a maximum of 110 mg/gFW between the 4th and the
      15th day of culture growth on APM. The major compound of the phenolic mixture was
      3,5-dicaffeoylquinic acid with maximum accumulation level of 80 mg/100 gFW. The
      potential effects of targeted phenolic compounds on the nutraceutical qualities
      of in vitro produced anthocyanin-rich extracts are discussed.

PMID- 15577192
TI  - Bioavailability and Biokinetics of Anthocyanins From Red Grape Juice and Red
      Wine.
AB  - In a comparative study, 9 healthy volunteers ingested a single oral dose of 400
      mL red grape juice or red wine with dose-adjusted anthocyanin content ( $283.5$
      mg or $279.6$ mg, resp.) in crossover. The content of anthocyanin glucosides was
      detected in plasma and urinary excretion. Additionally, the plasmatic antioxidant
      activity was assessed after intake. Based on the plasma content, biokinetic
      criteria of the single anthocyanins were calculated, such as AUC,
      $?mathrm{c}_{?mathrm{max}}$ , $?mathrm{t}_{?mathrm{max}}$ , and the elimination
      rate $?mathrm{t}_{1/2}$ . The urinary excretion of total anthocyanins differed
      significantly and amounted to $0.18$ % (red wine) and $0.23$ % (red grape juice)
      of the administered dose. Additionally, the plasmatic antioxidant activity
      increased to higher levels after juice ingestion compared to wine. The intestinal
      absorption of the anthocyanins of red grape juice seemed to be improved compared
      to red wine, suggesting a possible synergistic effect of the glucose content of
      the juice. The improved absorption resulted in an enhanced plasmatic bioactivity.

PMID- 15577193
TI  - New Family of Bluish Pyranoanthocyanins.
AB  - The use of anthocyanins has been investigated for the preparation of food and
      beverage natural colorants as they seem to have nontoxic effects. In this
      context, vinylpyranoanthocyanins were recently found to naturally occur in ageing
      red wine. This new family of anthocyanin-derived pigments may be obtained
      directly through the reaction between anthocyanin derivatives and other
      compounds. Some of these newly formed pigments have been found to exhibit a
      bluish color at acidic pH. The formation of bluish pigment was obtained through
      reaction between anthocyanin-pyruvic-acid adducts and flavanols in the presence
      of acetaldehyde. The formation of similar bluish pigments was attempted using
      other different precursors. The chromatic features of this kind of pigments bring
      promising expectations concerning the use of these naturally occurring blue
      pigments in the food industry.

PMID- 15577194
TI  - Anthocyanins and Human Health: An In Vitro Investigative Approach.
AB  - Anthocyanin pigments and associated flavonoids have demonstrated ability to
      protect against a myriad of human diseases, yet they have been notoriously
      difficult to study with regard to human health. Anthocyanins frequently interact
      with other phytochemicals to potentiate biological effects, thus contributions
      from individual components are difficult to decipher. The complex, multicomponent
      structure of compounds in a bioactive mixture and the degradation of flavonoids
      during harsh extraction procedures obscure the precise assignment of bioactivity
      to individual pigments. Extensive metabolic breakdown after ingestion complicates
      tracking of anthocyanins to assess absorption, bioavailability, and accumulation
      in various organs. Anthocyanin pigments and other flavonoids that are uniformly,
      predictably produced in rigorously controlled plant cell culture systems can be a
      great advantage for health and nutrition research because they are quickly,
      easily isolated, lack interferences found in whole fruits, can be elicited to
      provoke rapid and prolific accumulation, and are amenable to biolabeling so that
      metabolic fate can be investigated after ingestion.

PMID- 15577195
TI  - Nature's Swiss Army Knife: The Diverse Protective Roles of Anthocyanins in
      Leaves.
AB  - Anthocyanins, the pigments responsible for spectacular displays of vermilion in
      the leaves of deciduous trees, have long been considered an extravagant waste of
      a plant's resources. Contemporary research, in contrast, has begun to show that
      the pigments can significantly influence the way a leaf responds to environmental
      stress. Anthocyanins have been implicated in tolerance to stressors as diverse as
      drought, UV-B, and heavy metals, as well as resistance to herbivores and
      pathogens. By absorbing high-energy quanta, anthocyanic cell vacuoles both
      protect chloroplasts from the photoinhibitory and photooxidative effects of
      strong light, and prevent the catabolism of photolabile defence compounds.
      Anthocyanins also mitigate photooxidative injury in leaves by efficiently
      scavenging free radicals and reactive oxygen species. Far from being a useless by
      product of the flavonoid pathway, these red pigments may in some instances be
      critical for plant survival.

PMID- 15577196
TI  - Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins.
AB  - Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits
      and vegetables of red-blue color. Epidemiological investigations and animal
      experiments have indicated that anthocyanins may contribute to cancer
      chemoprevention. The studies on the mechanism have been done recently at
      molecular level. This review summarizes current molecular bases for
      anthocyanidins on several key steps involved in cancer chemoprevention: (i)
      inhibition of anthocyanidins in cell transformation through targeting mitogen
      activated protein kinase (MAPK) pathway and activator protein 1 (AP-1) factor;
      (ii) suppression of anthocyanidins in inflammation and carcinogenesis through
      targeting nuclear factor kappa B (NF- $?kappa$ B) pathway and cyclooxygenase 2
      (COX-2) gene; (iii) apoptotic induction of cancer cells by anthocyanidins through
      reactive oxygen species (ROS) / c-Jun NH(2)-terminal kinase (JNK)-mediated
      caspase activation. These data provide a first molecular view of anthocyanidins
      contributing to cancer chemoprevention.

PMID- 15577197
TI  - Quantification and Purification of Mulberry Anthocyanins with Macroporous Resins.
AB  - Total anthocyanins in different cultivars of mulberry were measured and a process
      for the industrial preparation of mulberry anthocyanins as a natural food
      colorant was studied. In 31 cultivars of mulberry, the total anthocyanins,
      calculated as cyanidin 3-glucoside, ranged from $147.68$ to $2725.46$ mg/L juice.
      Extracting and purifying with macroporous resins was found to be an efficient
      potential method for the industrial production of mulberry anthocyanins as a food
      colorant. Of six resins tested, X-5 demonstrated the best adsorbent capability
      for mulberry anthocyanins (91 mg/mL resin). The adsorption capacity of resins
      increased with the surface area and the pore radius. Residual mulberry fruit
      juice after extraction of pigment retained most of its nutrients, except for
      anthocyanins, and may provide a substrate for further processing.

PMID- 15577198
TI  - The Effect of Two Methods of Pomegranate (Punica granatum L) Juice Extraction on
      Quality During Storage at $4^?circ$ C.
AB  - The effect of two extraction methods of pomegranate juice on its quality and
      stability was evaluated. The first method consisted of separation of the seeds
      from fruits and centrifugation. The second method consisted of squeezing fruit
      halves with an electric lemon squeezer. During a period of 72 hours of cold
      storage at $4^?circ$ C, the juices were evaluated for the presence of sugars,
      organic acids, and anthocyanins. Delphinidin 3-glucoside was identified to be the
      major anthocyanin present at the level of 45-69 mg/L. Among the organic acids,
      oxalic and tartaric acids dominated. The major sugars detected in pomegranate
      juice were glucose and sucrose. No significant differences in the content of
      sugars, organic acids, or anthocyanins in juices obtained through application of
      the two different extraction methods were detected, with the exception of the
      drastic decrease of cyanidin $3,5$ -diglucoside level in juice obtained by seed
      centrifugation. The pH did not show differences between treatments. Titrable
      acidity and the level of sugars expressed as ${}^{?circ}$ Brix decreased after 32
      and 15 hours after extraction, respectively, when juice was obtained by
      centrifuging the seeds.

PMID- 15577199
TI  - Anthocyanin Concentration of "Assaria" Pomegranate Fruits During Different Cold
      Storage Conditions.
AB  - The concentration of anthocyanins in fruits of "Assaria" pomegranate, a sweet
      Portuguese cultivar typically grown in Algarve (south Portugal), was monitored
      during storage under different conditions. The fruits were exposed to cold
      storage ( $5^{?circ}$ C) after the following treatments: spraying with wax;
      spraying with $1.5$ % CaCl(2); spraying with wax and $1.5$ % CaCl(2); covering
      boxes with 25 $?mu$ c thickness low-density polyethylene film. Untreated fruits
      were used as a control. The anthocyanin levels were quantified by either
      comparison with an external standard of cyanidin 3-rutinoside (based on the peak
      area) or individual calculation from the peak areas based on standard curves of
      each anthocyanin type. The storage time as well as the fruit treatment prior to
      storage influenced total anthocyanin content. The highest levels were observed at
      the end of the first month of storage, except for the fruits treated with
      CaCl(2), where the maximal values were achieved at the end of the second month.
      The anthocyanin quantification method influenced the final result. When total
      anthocyanin was calculated as a sum of individual pigments quantified based on
      standard curves of each anthocyanin type, lower values were obtained.

PMID- 15577200
TI  - Urinary Excretion of Cyanidin Glucosides and Glucuronides in Healthy Humans After
      Elderberry Juice Ingestion.
AB  - In a pilot study with 6 females and 1 male, the metabolism of various cyanidin
      glucosides after oral administration of elderberry juice was investigated. The
      anthocyanin metabolites were detected in urinary excretion. After ingestion of a
      bolus quantity of $3.57$ g total anthocyanins in a $150$ mL elderberry juice
      concentrate, $0.053$ % of the administered dose was excreted in urine as
      glucosidically bound cyanidins within the first 5 hours. Only $0.003$ % of the
      ingested anthocyanin glucosides was excreted as cyanidin glucuronide, suggesting
      that this conversion step might be of minor importance in urinary excretion.

PMID- 15577201
TI  - N-cadherin plays a role in the synapse-like structures between mast cells and
      neurites.
AB  - Communication between nerves and mast cells is a prototypic demonstration of
      neuro-immune interaction. Numerous studies have shown that the stimulation of
      nerves (or addition of neurotransmitters) can evoke activation of mast cells, and
      that mast cell-derived mediators can influence neuronal activity. However, the
      molecules involved in the membrane-membrane contacts between nerves and mast
      cells are still unknown. Here, we used an in vitro co-culture approach comprising
      interaction between immune (bone marrow-derived mast cell, BMMC) and nerve cells
      (superior cervical ganglia, SCG). The experiments showed clearly that the nerve
      mast cell communication was supported by synapse-like structure and that N
      cadherin, not E-cadherin, played an essential role in the synapse-like structure.
      In addition, we found that the synapse-like structure was assisted by clustering
      of beta-catenin to N-cadherin.

PMID- 15577202
TI  - Casein kinase 2 (CK2)-mediated reduction of the activities of Src family tyrosine
      kinases in vitro.
AB  - The physiological correlation between casein kinase 2 (CK2) and two Src family
      tyrosine kinases (Src-TKs, Fyn and Src) was mainly investigated in vitro. It was
      found that (i) Thr-residues of these two Src-TKs were preferentially
      phosphorylated by CK2 using [gamma-32P]GTP as a phosphate donor; (ii) this
      phosphorylation was highly stimulated in the presence of poly-Arg; (iii) full
      phosphorylation of two Src-TKs by CK2 resulted in significant reduction of their
      TK activities; and (iv) quercetin (a CK2 inhibitor) inhibited the CK2-mediated
      reduction of their Src-TK activities in vitro. Under the same experimental
      conditions, similar results were obtained with Yes. These results suggest that
      CK2 may be a protein kinase responsible for the suppression of at least three Src
      TKs (Fyn, Src and Yes) through the specific phosphorylation of their Thr-residues
      at the cellular level.

PMID- 15577203
TI  - Interindividual variability in 2-hydroxylation, 3-sulfation, and 3
      glucuronidation of ethynylestradiol in human liver.
AB  - In the current study, we investigated interindividual variability of the 2
      hydroxylation, 3-glucuronidation, and 3-sulfation of ethynylestradiol (EE2) using
      human liver microsomes and cytosol. Km values for the 2-hydroxylation and 3
      glucuronidation in pooled liver microsomes and for the 3-sulfation in pooled
      liver cytosol were 3.34, 23.3, and 2.85 microM, respectively. Vmax/Km (ml/min/g
      liver) was highest for the 3-sulfation, followed by 2-hydroxylation, suggesting
      that 3-sulfation is the major metabolic pathway of EE2 in human liver. All
      further studies were performed at a substrate concentration of 0.1 microM.
      Microsomal 2-hydroxylation and 3-glucuronidation activities ranged from 0.21 to
      5.02 (2.04+/-1.34, mean+/-S.D., n=35) and 0.20 to 4.84 (1.20+/-1.00, n=35)
      pmol/min/mg protein, respectively. Cytosolic 3-sulfation activity ranged from 4.2
      to 24.3 (11.8+/-4.4, n=21) pmol/min/mg protein. All the measured enzyme
      activities were neither gender-related nor age-dependent, except that 2
      hydroxylation was significantly higher in females than in males (p<0.05). The
      relative contribution of CYP3A to the 2-hydroxylation in liver microsomes was
      estimated from the degree of inhibition by 1 microM ketoconazole. The degrees of
      inhibition were between 17.8 and 78.0% (51.6+/-16.0%, n=27). These results
      indicate that there are large interindividual differences in the enzyme
      activities towards the respective metabolic pathways of EE2 and the relative
      contribution of CYP3A to the 2-hydroxylation of EE2 in human liver.

PMID- 15577204
TI  - Endogenous hyaluronan: a cytokine-like factor present in rabbit uterine cervix
      during pregnancy.
AB  - The effects of endogenous hyaluronan on cervical ripening during pregnancy were
      examined in rabbits. Hyaluronan of approximately 620 kilodalton (kDa) was
      detected in the uterine cervix on the 25th and 29th days of pregnancy, while it
      was not detected in cervix of non-pregnant animals. In addition, low-molecular
      weight (less than 191 kDa) hyaluronan was present in cervix at the 29th day of
      pregnancy. Hyaluronan level in the cervix was lower on the 29th day than on the
      25th day of pregnancy, whereas that in serum was significantly higher on the 29th
      day than on the 25th day of pregnancy. To clarify the physiological functions of
      endogenous hyaluronan, the effects of hyaluronan (HA600-700), which had
      approximately equal to endogenous hyaluronan, on uterine cervical tissues and
      uterine cervical fibroblasts were examined. Rabbits at the 23rd day of pregnancy
      were administered a vaginal suppository of HA600-700 (20 mg) daily for three
      days. Promotion of cervical ripening was observed, as well as detachment of
      collagen fiber bundles, and a reduced density of collagen fiber distribution.
      Total collagenolytic activity was increased significantly by HA600-700 (1.0
      mg/ml) treatment in cultured uterine cervical explants of pregnant rabbits as
      compared with the untreated group. Moreover, very similar effects of HA600-700
      treatment (0.1, 1.0 mg/ml) were observed in cultured uterine cervical
      fibroblasts. Further, in tissue cultures, but not cell cultures, of pregnant
      rabbit cervix, prostaglandin E2 (PGE2) production was enhanced by HA600-700
      treatment. Therefore, it appears that endogenous hyaluronan is closely concerned
      with cervical ripening and dilatation in uterine cervix of pregnant rabbits.

PMID- 15577205
TI  - Uptake of gallium-67 by the hepatocytes during liver regeneration in carbon
      tetrachloride-treated mice.
AB  - Gallium-67 (67Ga) has been used as a tumor or inflammation-imaging agent in
      nuclear medicine. We recently reported that the peak of serum alanine
      aminotransferase (ALT) level was 1 d after carbon tetrachloride (CCl4) treatment
      in rats. However, the peak of 67Ga uptake by the liver tissue and hepatocytes was
      2 d after the treatment. If 67Ga is taken in the hepatic disorder phase, the
      pattern of 67Ga uptake by the hepatocytes should be consistent with that of the
      ALT level. In order to answer why it was not, we carried out a detailed
      examination. The lipid peroxidation of hepatocytes from CCl4-treated mice was
      greatly increased 1 d after CCl4 treatment; serum ALT was also increased 1 d
      after the treatment. The uptake of 67Ga by the liver tissue reached a maximum 1
      and 2 d after the treatment, while maximum by the hepatocytes was achieved after
      2 d. The incorporation of bromodeoxyuridine into the hepatocytes also reached
      maximum 2 d after the treatment. These results suggest that the uptake of 67Ga by
      the hepatocytes is carried out during liver regeneration rather than during
      hepatic disorder by CCl4 treatment.

PMID- 15577206
TI  - Membrane localization of transporter associated with antigen processing (TAP)
      like (ABCB9) visualized in vivo with a fluorescence protein-fusion technique.
AB  - Transporter associated with antigen processing (TAP)-like (TAPL, ABCB9) is a half
      type ATP binding cassette (ABC) protein belonging to subfamily B highly
      homologous to the TAP, a hetero-dimeric complex consisting of a TAP1 and a TAP2
      subunit. Human TAPL, to which was tagged with green fluorescence protein (GFP) at
      its carboxyl terminus (TAPL-GFP), showed fluorescence on intracellular membranes
      similar to TAP1-GFP. A truncated form of TAPL-L-GFP (M1-S275 was followed by GFP)
      showed a similar cellular fluorescence pattern to TAPL-GFP. However, the
      fluorescence of TAPL-S-GFP (M1-G75) was distributed over all the cellular
      membranes including plasma membrane, indicating that the amino terminal region of
      TAPL (M1-S275) is essential for its localization to the intracellular membranes.
      A co-expression study demonstrated that TAPL-S-GFP was co-localized with TAPL-DR
      (DsRed-tagged TAPL) or TAP1-DR, suggesting that TAPL is able to interact with not
      only itself but also with TAP1 through the M1-G75 region of TAPL. It is also
      proposed that a further downstream sequence of TAPL would confine the
      distribution of TAPL-S-GFP to the intracellular membranes. Similarly, the
      distribution of TAP2-S-GFP (M1-R88) was restricted to the intracellular membranes
      by TAPL-DR or TAP1-DR, indicating that the M1-R88 region of TAP2 is able to
      interact with TAPL as well as TAP1. Therefore, TAPL would form a homo-dimer with
      itself, and a hetero-dimer with TAP1 and TAP2. TAPL-GFP was co-localized with the
      fluorescence endoplasmic reticulum (ER) marker, suggesting that TAPL is mainly
      localized to the ER in the intracellular membranes.

PMID- 15577207
TI  - Phosphoproteome analysis of hereditary cataractous rat lens alpha-crystallin.
AB  - We reported previously that C-terminal truncated alpha-crystallins were found in
      lenses of hereditary cataractous rat ICR/f. In this study, we examined the
      phosphorylation of the crystalline lens proteins, alphaB-crystallin and alphaA
      crystallin, in cataractous and normal rats of different ages and have found an
      increase in the phosphorylation of serine residues of truncated alpha-crystallin
      in cataractous lens. Phosphorylation and C-terminal truncation of alpha
      crystallins could, both, reduce their chaperone-like activity and lead to
      cataract formation.

PMID- 15577208
TI  - Terminal telomere repeats are actually short in telomerase-negative immortal
      human cells.
AB  - Telomerase-negative immortal human cells maintained telomere length by a
      mechanism called alternative lengthening of telomeres (ALT mechanism). These
      cells (ALT cells) have two prominent characteristics of long telomere repeats at
      each chromosome end revealed by Southern blotting (terminal restriction
      fragments: TRF) and the presence extrachromosomal telomere repeat (ECTR) DNA. We
      report here that the TRF length of ALT cells revealed by the conventional
      unidirectional (UD) current or pulse-field (PF) current electrophoresis appeared
      to be over estimated. The TRF length determined by the pulse inverse-field (PIF)
      current electrophoresis (2-9 kbp depending upon cell lines) was much smaller than
      that (ca. 23 kbp) by UD or PF current electrophoresis. These results were in
      consistent with very weak telomere staining in situ at chromosome ends in ALT
      cells. When a mixture of HinfI-digested genomic DNA of human diploid fibroblasts
      and synthetic telomere repeat DNA with similar size of ECTR DNA was
      electrophoresed using a UD current, the apparent TRF size shifted to larger
      molecular weight, while the size shift did not occur by PIF current
      electrophoresis. These results together with other data indicate that the
      unusually long TRF of ALT cells determined by using conventional electrophoresis
      is an artifact produced by a complex formed by short TRF and short ECTR DNA.

PMID- 15577209
TI  - Characterization of two isoforms of mouse 3(17)alpha-hydroxysteroid
      dehydrogenases of the aldo-keto reductase family.
AB  - Mouse kidney contains two 3(17)alpha-hydroxysteroid dehydrogenases (HSDs) that
      show essentially the same properties except for their isoelectric points.
      However, the structural differences and physiological roles of the two enzymes
      remain unknown. In this study, we have isolated cDNAs for the two 3(17)alpha-HSDs
      from a total RNA sample of mouse kidney by reverse transcription-PCR. The
      identity of the cDNAs was confirmed by characterization of the recombinant
      enzymes that showed the same molecular weights, pI values, pH optima, substrate
      specificity and inhibitor sensitivity as those of the enzymes from mouse kidney.
      We also found that the recombinant enzymes reduce precursors of neuroactive
      progesterone derivatives, 5alpha-dihydrotestoserone, deoxycorticosterone,
      dehydroepiandrosterone, dehydroepiandrosterone sulfate and estrone at low Km
      values of 0.3-2 microM. The two enzymes belonged to the aldo-keto reductase (AKR)
      family, and their 323-amino acid sequences differed only by five amino acids. The
      sequences of the two isoforms are identical to those of proteins that are
      predicted to be encoded in a gene for AKR1C21 in the database of the mouse
      genome. However, the mRNAs for the two isoforms were expressed in mouse kidney
      and other tissues, in which their expression levels were different. The results
      indicate an important role of 3(17)alpha-HSD in controlling the concentrations of
      various steroid hormones in the mouse tissues, and suggest the existence of two
      genes for the two isoforms of the enzyme.

PMID- 15577210
TI  - Immunomodulatory effect of Astragali Radix extract on murine TH1/TH2 cell lineage
      development.
AB  - Astragali Radix (AR), is a popular herbal medicine used to treat allergic
      diseases in Korea, Japan and China. Our study examined the effect of an AR
      ethanol extract on both in vitro and in vivo murine CD4 T cells' differentiation
      into Th1 and Th2 subsets. CD4 T cells from Balb/c mice were activated with anti
      CD3/anti-CD28 mAb in the presence of AR for 2 d. AR treated cells showed an
      elevated level of IL-4 but a reduced level of IFN-gamma secretion. In addition,
      in vitro Th1/Th2 polarization experiments revealed that AR enhanced the levels of
      IL-4 in Th2 cells but reduced the levels of IFN-gamma in Th1 cells. To elucidate
      the effects of AR in Th1/Th2 lineage development during the in vivo condition, AR
      was administrated orally to BALB/c mice. The results demonstrated that AR
      administration significantly increased IL-4 production in both the serum and
      supernatant of splenocyte culture, while IFN-gamma secretion was diminished upon
      in vivo activation with anti-CD3 antibody. Our data clearly indicates that AR
      selectively alters Th1/Th2 cytokine secretion patterns and provides the
      pharmacological basis for AR's clinical applications.

PMID- 15577211
TI  - Nicotinic enhancement of proliferation in bovine and porcine cerebral
      microvascular endothelial cells.
AB  - Nicotinic acetylcholine receptors are found in microvascular endothelial cells.
      To reveal the functional role in cerebral angiogenic processes, we studied the
      nicotinic modulation of proliferation activity in cultured bovine and porcine
      cerebral microvascular endothelial cells. The proliferation activity was
      determined by an increase in the number of cells present in culture dishes. When
      the bovine cerebral endothelial cells at different passages were cultured in the
      presence of nicotine (10 nM), the proliferation activities were significantly
      increased in the cells at passage 1 and passage 3, but not at passage 4. Reverse
      transcriptase-polymerase chain reaction studies demonstrated that the expression
      of mRNAs coding for alpha3 nicotinic receptor subunit was significantly reduced
      in the bovine cerebral endothelial cells at passage 4, compared with that at
      passage 1. The proliferation of porcine cerebral endothelial cells (passage 1)
      was enhanced by acetylcholine (10 nM-100 microM) in the presence of atropine, a
      muscarinic antagonist, and this enhancing effect was inhibited by hexamethonium
      (100 microM, a nicotinic antagonist). The stimulation by acetylcholine (1 microM,
      with atropine) or nicotine (10 nM) induced the phosphorylation of a mitogen
      activated protein (MAP) kinase (extracellular-signal regulated kinase: ERK) in
      the serum-starved endothelial cells. In the presence of PD98059 (2 microM, a MAP
      kinase kinase inhibitor) and atropine, acetylcholine (1 microM) failed to enhance
      the proliferation of porcine cerebral endothelial cells. These results
      demonstrate that nicotinic stimulation promotes the proliferation of bovine and
      porcine cerebral microvascular endothelial cells, at least in part, through the
      MAP kinase activation.

PMID- 15577212
TI  - Hepatoprotective effect of extracts from Lentinus edodes mycelia on
      dimethylnitrosamine-induced liver injury.
AB  - Mycelia of the edible mushroom Lentinus edodes (shiitake) were cultivated in a
      solid medium, and two fractions were obtained by hot-water extraction (L.E.M.)
      and then ethanol extraction followed by Sephadex LH-20 column chromatography
      (ESMe). The L.E.M. and ESMe were then examined for their hepatoprotective effect
      on dimethylnitrosamine-injured mice. Both fractions decreased the blood aspartate
      aminotransferase and alanine aminotransferase levels, partially inhibited the
      overaccumulation of collagen fibrils, and suppressed the overexpression of genes
      for alpha-smooth muscle actin and/or heat-shock protein 47 in the mice. Both
      fractions also inhibited the morphologic change and proliferation of isolated rat
      hepatic stellate cells (HSCs), which play a central role in liver fibrosis, in a
      dose-dependent manner and without cytotoxicity. The direct interaction between
      the extracts and HSCs appears to be important for the hepatoprotective activity.
      Polyphenols contained in both fractions are considered to be potential candidates
      for expressing the hepatoprotective effects. The finding of antifibrotic activity
      in extracts from an edible mushroom is expected to be helpful in the development
      of hepatoprotective agents with few side effects.

PMID- 15577213
TI  - The effect of Eriobotrya japonica seed extract on oxidative stress in adriamycin
      induced nephropathy in rats.
AB  - Eriobotrya japonica has been used as a medicinal plant for a long time, and its
      leaves are known to have many physiological actions such as anti-inflammatory,
      antitussive, and expectoran. In contrast, Eriobotrya japonica seeds are only
      known to contain amygdalin, and almost no investigations of its pharmacological
      action have been performed. Moreover, some anticancer agents such as adriamycin
      cause renal disorders as an adverse effect, and the mechanism of the adverse
      effect is considered to involve oxidative stress. We have reported that
      Eriobotrya japonica seed extract has an inhibitory effect on liver disorders. In
      this study, we prepared a 70% ethanol extract of Eriobotrya japonica seeds and
      administered the extract to rats with renal disorder induced by a single
      administration of 7 mg/kg body weight adriamycin, and investigated the usefulness
      of the extract. Increases in indices of renal function, plasma urea nitrogen,
      were significantly inhibited in rats treated with the Eriobotrya japonica extract
      compared to rats treated with tap water. In addition, the renal tissue level of
      reduced glutathione was significantly high in rats that ingested the extract,
      while the lipid peroxide levels in plasma and renal tissue were significantly
      low. However, no effect on renal tissue antioxidative enzymes was observed,
      suggesting that Eriobotrya japonica seed extract has direct antioxidative action.
      Based on these findings, Eriobotrya japonica seed extract may be effective in
      reducing the oxidative stress of adriamycin-induced renal disorder. Therefore,
      ingestion of Eriobotrya japonica seed extract may contribute to a reduction of
      the adverse effects of adriamycin.

PMID- 15577214
TI  - Antimicrobial activity of 10 different plant polyphenols against bacteria causing
      food-borne disease.
AB  - The antibacterial activities of 10 different plant polyphenols were evaluated by
      comparing their minimum inhibitory concentrations (MICs) against several food
      borne pathogenic bacteria, Staphylococcus aureus (20 strains), some serotypes of
      the genus Salmonella (26 strains), Escherichia coli (23 strains), and some
      species of the genus Vibrio (27 strains). The polyphenols examined were
      epigallocatechin (1), epigallocatechin-3-O-gallate (2), punicalagin (3), tannic
      acid (4), castalagin (5), prodelphinidin (6), geraniin (7), procyanidins (8), a
      theaflavin mixture of black tea (9), and green tea polyphenols treated with
      loquat polyphenol oxidase (10). The average MICs of all polyphenols against S.
      aureus and the genus Vibrio (192+/-91 and 162+/-165 microg/ml, respectively) were
      much lower than the values against the genus Salmonella and E. coli (795+/-590
      and 1519+/-949 microg/ml, respectively) (p<0.01). The coefficient of variation of
      the MICs of all polyphenols against S. aureus was the least and that against the
      genus Vibrio was the greatest. The mean MICs of each plant polyphenol against S.
      aureus (98-389 microg/ml) and the genus Vibrio (68-488 microg/ml) were similar.
      The relatively lower mean MIC values of 1, 2, 5, and 6 suggest the importance of
      3,4,5-trihydroxyphenyl groups in antibacterial activity.

PMID- 15577215
TI  - Evaluation of cell death caused by triterpene glycosides and phenolic substances
      from Cimicifuga racemosa extract in human MCF-7 breast cancer cells.
AB  - We previously reported that the antiproliferative effect of an isopropanolic
      aqueous extract of black cohosh (iCR) on MCF-7 estrogen-responsive breast cancer
      cell line was due to the induction of apoptosis. Here we address the question to
      what extent apoptosis induction can be ascribed to one of the two major fractions
      of iCR, the triterpene glycosides (TTG) or the cinnamic acid esters (CAE).
      Furthermore, as black cohosh is routinely administered orally, we studied whether
      its pharmacological effects would withstand simulated liver metabolism. The
      antiproliferative activity of TTG and CAE as well as of rat liver microsomal S9
      fraction-pretreated iCR on MCF-7 cells were investigated by WST-1 assay. The
      features of cell death induced were tested for apoptosis by flow cytometry (light
      scatter characteristics, Annexin V binding). Irrespective of S9-pretreatment, 72
      h iCR treatment induced a dose-dependent down regulation of cell proliferation
      with the same IC50 of 55.3 microg/ml dry residue which corresponds to 19.3
      microg/ml TTG and 2.7 microg/ml CAE. The degree of apoptotic MCF-7 cells was also
      comparable. Both, isolated TTG and CAE fractions inhibited cell growth, the IC50
      being 59.3 microg/ml and 26.1 microg/ml, respectively. Interestingly, whereas
      IC50 and apoptosis induction correspond well for the whole extract, TTG and CAE
      fractions induced apoptosis at concentrations (25 and 5 microg/ml) well below
      those required for significant growth inhibition. Observation of this study
      firstly showed that the cell death induced by iCR withstood a metabolic
      activation system. In addition, TTG and CAE compounds significantly contributed
      to its apoptotic effect, CAE being the more potent inhibitor of proliferation and
      apoptosis inducer.

PMID- 15577216
TI  - Inhibitory effects of active compounds isolated from safflower (Carthamus
      tinctorius L.) seeds for melanogenesis.
AB  - In order to develop a new skin whitening agent, safflower (Carthamus tinctorius
      L.) seeds were evaluated for melanogenesis inhibitory activity and its active
      principles were identified following activity-guided isolation. The 80% aqueous
      methanol extract and ethyl acetate fraction from safflower seeds showed a
      significant inhibition for mushroom tyrosinase. Three active compounds, N
      feruloylserotonin, N-(p-coumaroyl)serotonin, and acacetin, were isolated from the
      ethyl acetate fraction as the active principles. Compared with arbutin
      (IC50=0.223 mM), the IC50 values of these compounds were 0.023, 0.074, and 0.779
      mM for N-feruloylserotonin, N-(p-coumaroyl)serotonin, and acacetin, respectively.
      It was also found that N-feruloylserotonin and N-(p-coumaroyl)serotonin strongly
      inhibited the melanin production of Streptomyces bikiniensis and B16 melanoma
      cells in comparison with a known melanogenesis inhibitor, arbutin.

PMID- 15577217
TI  - cDNA isolation and functional expression of myrcene synthase from Perilla
      frutescens.
AB  - cDNA cloning of a monoterpene synthase from Perilla frutescens whose steam
      distilled oil contains 92.9% perillaketone, was performed by the PCR method using
      primers designed based on limonene synthase. The full-length nucleotide sequence
      of this cDNA consisted of 1978 bp including a 1827-bp translational region
      encoding a deduced protein of 608 amino acids, which was similar to that of
      limonene synthase from P. frutescens (85% identity). Functional expression of
      this clone in Escherichia coli yielded an active monoterpene synthase enzyme,
      which converted geranyl diphosphate into 53.8% myrcene, 20.9% sabinene, 19.8%
      linalool and 5.5% limonene. As for the extraction of reaction products, we
      performed SPME (solid phase micro extraction) as well as conventional solvent
      extraction, and compared these two extraction methods.

PMID- 15577218
TI  - Short term Caco-2/TC7 cell culture: comparison between conventional 21-d and a
      commercially available 3-d system.
AB  - The Caco-2 cell model is a valuable tool for studying intestinal
      biotransformation of xenobiotics and to evaluate the potential of human
      intestinal absorption of new compounds. These properties were evaluated with Caco
      2/TC7 cells in accelerated conditions to reduce maturation lag time from 21-d to
      3-d in order to increase time and labor efficiency. Transmission electron and
      fluorescent microscopy were used for morphological characterization. Alkaline
      phosphatase and lactate dehydrogenase activities were assessed within time.
      Cytochrome P450 expression was studied by RT-PCR. Apparent permeabilities of a
      set of passively absorbed molecules across Caco-2/TC7 cell monolayers were
      determined to evaluate potential of both systems for prediction of human
      intestinal absorption. Microscopic images revealed that cells under both
      conditions differentiated as enterocyte-like cells but did so heterogeneously in
      the 3-d model. TEER values have shown that the 3-d model is a leakier cell system
      with higher mannitol Papp (cm/s). Biochemical characterization (hydrolase
      activities, CYP450 expression) suggested that the 3-d model was at a lower
      maturation level than the 21-d model. Carrier-mediated uptake of L-Phe was lower
      in the 3-d model suggesting that this model has limited application for
      mechanistic studies. Reasonable correlation was obtained between the two models
      (r2=0.88, p>0.01) for 11 passively absorbed compounds with high potential of rank
      ordering of compounds. Although results suggested that the 3-d cells are under
      differentiated, they could be usable to estimate the oral absorption of passively
      absorbed compounds.

PMID- 15577219
TI  - Formulation design of self-microemulsifying drug delivery systems for improved
      oral bioavailability of celecoxib.
AB  - Celecoxib is a hydrophobic and highly permeable drug belonging to class II of
      biopharmaceutics classification system. Low aqueous solubility of celecoxib leads
      to high variability in absorption after oral administration. Cohesiveness, low
      bulk density and compressibility, and poor flow properties of celecoxib impart
      complications in it's processing into solid dosage forms. To improve the
      solubility and bioavailability and to get faster onset of action of celecoxib,
      the self-microemulsifying drug delivery system (SMEDDS) was developed.
      Composition of SMEDDS was optimized using simplex lattice mixture design.
      Dissolution efficiency, t(85%), absorbance of diluted SMEDDS formulation and
      solubility of celecoxib in diluted formulation were chosen as response variables.
      The SMEDDS formulation optimized via mixture design consisted of 49.5% PEG-8
      caprylic/capric glycerides, 40.5% mixture of Tween20 and Propylene glycol
      monocaprylic ester (3:1) and 10% celecoxib, which showed significantly higher
      rate and extent of absorption than conventional capsule. The relative
      bioavailability of the SMEDDS formulation to the conventional capsule was 132%.
      The present study demonstrated the suitability of mixture design to optimize the
      compositions for SMEDDS. The developed SMEDDS formulations have the potential to
      minimize the variability in absorption and to provide rapid onset of action of
      celecoxib.

PMID- 15577220
TI  - Influence of coadministered antiepileptic drugs on serum phenobarbital
      concentrations in epileptic patients: quantitative analysis based on a suitable
      transforming factor.
AB  - This study investigated most suitable transforming factor related to the daily
      Phenobarbital dose (D) providing a steady-state serum concentration (Ct) and
      analyzed the influences of concomitant antiepileptic drugs on Ct quantitatively.
      Data obtained by routine therapeutic drug monitoring from a total of 326
      epileptic patients treated with multiple oral administrations of phenobarbital
      (PB) as a powder, were used for the analysis. A total of 156 patients were
      administered PB alone, and 92, 57, and 21 patients were coadministered one, two,
      and three different antiepileptic drugs, respectively. Valproic acid (VPA),
      carbamazepine (CBZ), phenytoin (PHT), zonisamide (ZNS), clonazepam, and
      ethosuximide were coadministered with PB. For administration of PB alone, four
      types of transforming factor corresponding to clearance, i.e., total body weight,
      total body water volume, body surface area and extracellular water volume (VECW)
      were proposed. With VECW as a transforming factor, the level/dose (L/D) ratio
      (:Ct/(D/VECW)) was independent of the patient's age and gender. Ct was dependent
      on only one variable regarding D/VECW and expressed as Ct=0.989 x (D/VECW). The
      coadministration of one drug caused a difference in the gradient of the
      regression line of PB alone, and the influence of each drug was detected by
      dividing each mean L/D ratio of PB plus one other drug by that of PB alone. VPA,
      CBZ, and PHT significantly increased (p<0.01) the L/D ratio to 1.48, 1.35, and
      1.23 of the value for PB alone, respectively. With coadministration of multiple
      drugs, the L/D ratio rose significantly (p<0.05) as the number (< or =2) of drugs
      coadministered increased regardless of the type, and also increased with the
      concomitant use of 3 drugs compared with 2 drugs. For a more detailed analysis,
      we defined the parameter eta(i) (i=1, 2, ..., 6) and an alteration ratio Ri,
      representing the influence of each antiepileptic drug on the L/D ratio of PB
      alone. A model based on the assumption that each coadministered drug
      competitively inhibited PB-metabolizing enzyme, was adopted. The analysis
      clarified that VPA, CBZ, and PHT significantly increased (p<0.05) the L/D ratio
      of PB to 1.466, 1.177, and 1.186, respectively. In the case of the addition or
      discontinuance of concomitant treatment with antiepileptic drugs in the same
      patient, the estimated L/D ratios were calculated using the value of each Ri and
      compared with the measured value. The mean of prediction error was calculated as
      23.1%. Our results appear valid and Ri should be available for clinical use.

PMID- 15577221
TI  - Studies on interactions between functional foods or dietary supplements and
      medicines. IV. Effects of ginkgo biloba leaf extract on the pharmacokinetics and
      pharmacodynamics of nifedipine in healthy volunteers.
AB  - The effects of Ginkgo biloba leaf extract (GBE), a widely used herbal dietary
      supplement in Japan, on the pharmacokinetics and pharmacodynamics of nifedipine
      (NFP), a calcium-channel blocker, were studied using 8 healthy volunteers.
      Simultaneous oral ingestion of GBE (240 mg) did not significantly affect any of
      the mean pharmacokinetic parameters of either NFP or dehydronifedipine, a major
      metabolite of NFP, after oral administration of NFP (10 mg). However, the maximal
      plasma NFP concentrations in 2 subjects were approximately doubled by GBE, and
      they had severer and longer-lasting headaches with GBE than without GBE, with
      dizziness or hot flushes in combination with GBE. The mean heart rate after oral
      administration of NFP with GBE tended to be faster than that without GBE at every
      time point. Accordingly, it was concluded that GBE and NFP should not be
      simultaneously ingested as much as possible, and careful monitoring is needed
      when administering NFP concomitantly with GBE to humans.

PMID- 15577222
TI  - Experimental analysis of antimicrobial action of dicyclomine hydrochloride.
AB  - Dicyclomine hydrochloride is an antispasmodic agent. The MIC of dicyclomine
      against standard strains of Gram positive and Gram negative bacteria were
      performed by NCCLS broth dilution technique. These drugs showed a rapid killing
      action on Gram positive bacteria, Staphylococcus aureus NCTC 6571, 8530 and
      several other reference strains. The killing effect against Gram negative
      bacteria, Shigella boydii 8 NCTC 254/66 and Salmonella typhimurium NCTC 74 showed
      that the drug was bacteriostatic with respect to these strains. High rate of
      killing was achieved for most strains of Gram positive bacteria within 2 h. When
      administered to Swiss strain of white mice at doses of 30 and 60 microg/g of
      mouse, the drug could significantly protect the animals challenged with 50 MLD of
      Salmonella typhimurium NCTC 74. According to chi2 test, the in vivo data were
      highly significant (p<0.001). Since dicyclomine showed a remarkable inhibitory
      action against several pathogenic bacteria, in the course of time, it may be
      developed as a potent antimicrobial agent for many bacterial infections.

PMID- 15577223
TI  - Aminopeptidase N/CD13 regulates the fetal liver microenvironment of
      hematopoiesis.
AB  - Fetal liver (FL) hematopoiesis is thought to be important for expanding the cell
      number during ontogeny. In order to investigate the cellular interaction
      molecules among FL stromal and hematopoietic cells, we established a monoclonal
      antibody, Ndk-10, that reacts with FL stromal cells but not with dish non
      adherent cells. When Ndk-10 was added to an FL stromal and hematopoietic cell
      coculture, it inhibited the survival of c-kit+ cells. The inhibitory activity of
      Ndk-10 was also observed in the fetal liver organ culture. The Ndk-10 recognized
      a 150 kD molecule in the adherent cells of FL and kidney, and the N-terminal
      amino acid sequence was identical to that of mouse aminopeptidase N/CD13. The
      peptidase activity of CD13 was inhibited by Ndk-10, and addition of its specific
      inhibitor resulted in the same inhibitory activity as Ndk-10. We propose that
      aminopeptidase N/CD13 is a critical molecule that regulates the survival of c
      kit+ cells in the FL microenvironment.

PMID- 15577224
TI  - Expression changes of the mRNA of Alzheimer's disease related factors in the
      permanent ischemic rat brain.
AB  - The rat with permanent occlusion of the bilateral common carotid arteries (2VO)
      is useful model for the study of dementia. The expression changes of amyloid
      precursor protein (APP), secretase, alpha7 nicotinic acetylcholine receptor
      (alpha7NicR) and acetylcholine esterase (AChE), which are involved in Alzheimer's
      disease, were examined by quantitative RT/PCR in this model rat brain. The
      expression of APP, alpha7NicR and secretase were increased 4 d after 2VO. The
      alpha7NicR level at 2 d after operation already tended to increase. These result
      suggest that alpha7NicR expression was enhanced at early stage of brain ischemia.
      Using this model to find drugs which regulate the alpha7NicR expression will be
      useful to assay the materials with anti-dementive effect.

PMID- 15577225
TI  - Protective effect of protocatechuic acid isopropyl ester against murine models of
      sepsis: inhibition of TNF-alpha and nitric oxide production and augmentation of
      IL-10.
AB  - Antioxidants have been shown to be effective in murine models of sepsis.
      Protocatechuic acid has antioxidant activity. In the present study, the
      protective effects of protocatechuic acid and its derivatives were investigated
      in a mouse model of septic shock induced by lipopolysaccharide (LPS)/D
      galactosamine (GalN). Pretreatment of animals with protocatechuic acid
      effectively suppressed LPS/GalN-induced lethality; protocatechuic acid isopropyl
      ester was the most effective among the various derivatives of protocatechuic
      acid. Protocatechuic acid isopropyl ester was also effective in protection
      against the high-dose LPS-induced shock. Pretreatment with protocatechuic acid
      isopropyl ester effectively suppressed the LPS/GalN-induced increase in plasma
      tumor necrosis factor (TNF)-alpha alanine aminotransferase (ALT), nitrite/nitrate
      levels, and hepatic malondialdehyde levels. In contrast, it markedly enhanced the
      LPS/GalN-induced increase in plasma interleukin (IL)-10 levels, without any
      changes in IL-6 plasma levels. These results suggest that protocatechuic acid
      isopropyl ester could be useful for the prevention of sepsis.

PMID- 15577226
TI  - Anti-inflammatory effect of Semecarpus anacardium Linn. Nut extract in acute and
      chronic inflammatory conditions.
AB  - The article relates to investigation of the anti-inflammatory effects of
      Semecarpus anacardium LINN. nut extract (SA), and also an anti-inflammatory drug,
      indomethacin, on carrageenan-induced paw edema and cotton pellet granuloma tests
      for their effects on acute and chronic phases of inflammation, respectively. The
      effect of SA on developing and developed adjuvant arthritis was also evaluated.
      SA significantly decreased the carrageenan-induced paw edema and cotton pellet
      granuloma. Indomethacin also decreased the acute and chronic phases of
      inflammation. SA decreased the adjuvant induced (arthritis) paw edema after the
      treatment, in both developing and developed adjuvant arthritis. These results
      indicate that the potent anti-inflammatory effect and therapeutic efficacy of
      Semecarpus anacardium LINN. nut extract against all phases of inflammation, is
      comparable to that of indomethacin.

PMID- 15577227
TI  - Effects of Ninjin-to on levels of calcitonin gene-related peptide and substance P
      in human plasma.
AB  - The herbal medicine Ninjin-to has been used for the treatment of gastroenteritis,
      esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. One of the
      mechanisms of the empirical effects is assumed to be due to local changes in
      neuropeptide levels. Sensory afferent neurons in the gastrointestinal mucosa
      regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P,
      etc.], which play various physiologic roles. To determine whether the
      pharmacologic effects of Ninjin-to on the gastrointestine are due to changes in
      gastrointestinal mucosa regulatory peptide levels, we examined the effects of
      Ninjin-to on the levels of CGRP-like immunoreactive substances (IS) and substance
      P-IS in plasma taken from five healthy subjects. A single oral administration of
      6.0 g of Ninjin-to caused significant increases in plasma CGRP-IS at 40 min and
      60 min, and in substance P-IS levels at 90 min, compared with a placebo group.
      These results may indicate that the pharmacologic actions of Ninjin-to are
      closely related to changes in CGRP-IS and substance P-IS levels.

PMID- 15577228
TI  - Isolation of angiotensin converting enzyme (ACE) inhibitory flavonoids from Sedum
      sarmentosum.
AB  - Bioassay-guided fractionation of the EtOAc-soluble extract of Sedum sarmentosum
      afforded a new flavonoid, quercetin-3-O-alpha-(6'''-caffeoylglucosyl-beta-1,2
      rhamnoside) (1), along with four known flavonoids, quercetin 3-O-alpha-(6'''-p
      coumaroylglucosyl-beta-1,2-rhamnoside) (2), isorhamnetin-3-beta-glucopyranoside
      (3), quercetin-3-beta-glucopyranoside (4), and kaempferol-3-alpha
      arabinopyranoside (5). Purification of these compounds was conducted with the
      application of various chromatographic methods. Compounds 1-5 inhibited
      angiotensin I converting enzyme (ACE) activity in a concentration-dependent
      manner. Compounds 1-5 had 50% inhibitory concentration values of 158.9+/-11.1
      microgM, 351.6+/-3.9 microgM, 408.9+/-4.6 microgM, 708.8+/-23.1 microgM, and
      392.8+/-13.4 microgM.

PMID- 15577229
TI  - Comparison of the nucleotide sequences of ferredoxin-cDNAs among some Datura
      plants.
AB  - The nucleotide sequences of partial ferredoxin (Fd)-cDNAs (corresponding to the
      amino acid sequence of 22-87 in the total 97 amino acids of ferredoxin) were
      determined for Datura arborea, D. stramonium, D. metel, and related Datura
      plants. Non-synonymous substitutions were noted at 4 positions and a synonymous
      substitution was seen at position 82 (Gln [CAA] (arborea) vs. Gln [CAG]
      (stramonium and metel)). The nucleotide sequence of Fd-cDNA may provide more
      detailed information regarding the relative taxonomic positions of plants than
      the amino acid sequence. However, Datura plants in the same section (metel,
      fastuosa, and innoxia) and of different varieties (stramonium var. stramonium and
      stramonium var. tatula) showed identical Fd-cDNA nucleotide sequences. This
      result suggests that there are very close relationships among the plants in each
      group.

PMID- 15577230
TI  - Studies on interactions between functional foods or dietary supplements and
      medicines. III. Effects of ginkgo biloba leaf extract on the pharmacokinetics of
      nifedipine in rats.
AB  - The effects of Ginkgo biloba leaf extract (GBE), one of the most widely used
      herbal dietary supplements in Japan and the United States, on the
      pharmacokinetics of nifedipine (NFP), a typical probe of P450 (CYP) 3A, but not a
      substrate of the multidrug transporter P-glycoprotein (P-gp), were studied using
      rats. Simultaneous oral treatment with GBE (20 mg/kg) did not affect the
      pharmacokinetics after intravenous administration of NFP (2.5 mg/kg). However,
      the maximal plasma NFP concentration, the area under the concentration-time curve
      and absolute bioavailability after oral administration of NFP (5 mg/kg) were
      significantly increased by simultaneous oral treatment with GBE, approximately
      1.6-fold, 1.6-fold and 2.1-fold, respectively. These results suggest that the
      concomitant oral use of GBE appeared to reduce the first-pass metabolism of
      orally administered NFP, by inhibiting CYP3A, possibly but not P-gp, in rats.

PMID- 15577231
TI  - Efficient gene transfer into human trophoblast cells with adenovirus vector
      containing chimeric type 5 and 35 fiber protein.
AB  - Recombinant adenovirus (Ad) vectors based on Ad type 5 have been widely used for
      gene transfer experiments. Conventional Ad type 5 vectors have a narrow range of
      tropism and are limited by the size of the transgene that can be packaged. To
      overcome these limitations, we previously developed an Ad vector (Ad5/35 vector)
      containing a chimeric Ad type 5 and 35 fiber protein. In the current study, we
      evaluated the ability of the Ad5/35 vector to transfer genes into human
      trophoblast cell lines (JAR, JEG-3 and BeWo cells), which are used as in vitro
      models of human placenta. We compared the gene transfer efficiency of Ad5/35 to
      that of conventional Ad vector. We found that expression of CD46, which are
      receptors for Ad5/35 vector, are higher than that of coxsackievirus and
      adenovirus receptor in all 3 trophoblast cell lines, as determined by flow
      cytometry. Next, we compared the transducing activity of Ad5 vector and Ad5/35
      vector that each expressed luciferase as a reporter gene. Ad5/35 vector had
      greater gene transfer activity than the conventional Ad vector in all 3
      trophoblast cell lines (1.82-fold in JAR cells, 5.37-fold in BeWo cells, 6.11
      fold in JEG-3 cells). Thus, Ad vector that contains chimeric type 5 and 35 fiber
      protein can be a powerful tool for gene transfer experiments in human trophoblast
      cell lines.

PMID- 15577232
TI  - Protective effect of montmorillonite on plasmid DNA in oral gene delivery into
      small intestine.
AB  - Montmorillonite, a bioinert clay mineral, was examined as a novel vector for an
      oral gene-delivery system. The complex of montmorillonite and plasmid DNA
      encoding the enhanced green fluorescent protein (EGFP) gene was prepared at
      various weight ratios, and then transfected into cultured intestinal epithelial
      cells (IEC-6) in vitro. The EGFP gene was clearly transcribed when the
      transfection was performed using the montmorillonite-plasmid complex at a weight
      ratio of 0.05:1. In contrast, no gene expression was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) analysis when the transfection
      was performed with naked plasmid. Various plasmid preparations were given orally
      to mice, and the gene expression in the stomach and small intestine was examined
      by RT-PCR. Although no gene expression was detected in the mice receiving an oral
      administration of naked plasmid or polyethyleneimine-plasmid complex, the EGFP
      gene complexed with montmorillonite was expressed in the small intestine. These
      results indicate that montmorillonite protected the plasmid DNA from the acidic
      environment in the stomach and DNA-degrading enzymes in the intestine, and
      successfully delivered it into cells of the small intestine.

PMID- 15577233
TI  - Development of bridged nucleic acid analogues for antigene technology.
AB  - In the last decade, increased efforts have been directed toward the development
      of oligonucleotide-based technologies for genome analyses, diagnostics, or
      therapeutics. Among them, an antigene strategy is one promising technology to
      regulate gene expression in living cells. Stable triplex formation between the
      triplex-forming oligonucleotide (TFO) and the target double-stranded DNA (dsDNA)
      is fundamental to the antigene strategy. However, there are two major drawbacks
      in triplex formation by a natural TFO: low stability of the triplex and
      limitations of the target DNA sequence. To overcome these problems, we have
      developed various bridged nucleic acids (BNAs), and found that the 2',4'-BNA
      modification of oligonucleotides strongly promotes parallel motif triplex
      formation under physiological conditions. Some nucleobase analogues to extend the
      target DNA sequence were designed, synthesized, and introduced into the 2',4'-BNA
      structure. The obtained 2',4'-BNA derivatives with unnatural nucleobases
      effectively recognized a pyrimidine-purine interruption in the target dsDNA. Some
      other examples of nucleic acid analogues for stable triplex formation and
      extension of the target DNA sequence are also summarized.

PMID- 15577234
TI  - Interaction of heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin with cholesterol
      in aqueous solution.
AB  - The interaction of cholesterol with heptakis (2,3,6-tri-O-methyl)-beta
      cyclodextrin (TOM-beta-CyD) was investigated in water using solubility method. It
      was found that TOM-beta-CyD forms two kinds of soluble complexes, with molar
      ratios of 1:1 and 1:2 (cholesterol:TOM-beta-CyD). The thermodynamic parameters
      for 1:1 and 1:2 complex formation of cholesterol with TOM-beta-CyD were:
      DeltaG0(1:1)=-11.0 kJ/mol at 25 degrees C (K1:1=7.70 x 10 M(-1)); DeltaH0(1:1)=
      1.28 kJ/mol; TDeltaS0(1:1)=9.48 kJ/mol; DeltaG0(1:2)=-27.8 kJ/mol at 25 degrees C
      (K1:2)=7.55 x 10(4) M(-1)); DeltaH0(1:2)=-0.57 kJ/mol; TDeltaS0(1:1)=27.3 kJ/mol.
      The formation of the 1:2 complex occurred much more easily than that of the 1:1
      complex. The driving force for 1:1 and 1:2 complex formation was suggested to be
      exclusively hydrophobic interaction. Based on the measurements of proton nuclear
      magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models,
      the probable structures of the 1:2 complex were estimated. In addition, the
      interaction of TOM-beta-CyD with cholesterol was compared with that of heptakis
      (2,6-di-O-methyl)-beta-CyD (DOM-beta-CyD). The interaction of TOM-beta-CyD is
      more hydrophobic than that of DOM-beta-CyD, and the life time of the complexed
      TOM-beta-CyD is sufficiently long to give separated signals, at the NMR time
      scale, which differs from that of complexed DOM-beta-CyD.

PMID- 15577235
TI  - Triterpenoid saponins from leaves of Hedera pastuchowii.
AB  - Five new triterpenoid saponins, pastuchoside A (1), B (3), C (5), D (7) and E
      (9), were isolated from the leaves of Hedera pastuchowii. They have oleanolic
      acid or hederagenin as aglycone. The structures were established by NMR
      spectroscopy including gs (gradient selected)-COSY, gs-HSQC, gs-HSQC-TOCSY and gs
      HMBC experiments, and mass spectrometry (ESI-HR-MS). Heptaoside saponins,
      compounds 1 and 3, are described for the first time in the genus Hedera.

PMID- 15577236
TI  - Quantitative taste evaluation of total enteral nutrients.
AB  - The purpose of this study was to evaluate quantitatively the taste of the various
      total enteral nutrients marketed in Japan using human gustatory sensation tests
      and an artificial taste sensor. In the human gustatory sensation test, four basic
      taste intensities (sweetness, saltiness, sourness, and bitterness), as well as 15
      kinds of palatability scales, were evaluated according to the semantic
      differential (SD) method. Among 15 palatability items, the item; difficult to
      drink/easy to drink, was adopted as an overall palatability since it shows the
      highest factor loading by factor analysis. The overall palatability was found to
      be highly positively correlated with sweetness and sourness, but negatively
      correlated with bitterness and saltiness. Addition of a flavour to the amino acid
      based enteral nutrient AminolebanEN significantly improved its palatability. This
      effect is presumably due to sour components of the flavour, such as citric acid,
      which reduce the bitterness intensity of branched-chain amino acids in the
      product. The sweetness and sourness intensities predicted by the taste sensor
      showed a high correlation with the results obtained in the human gustatory
      sensation tests. The taste sensor was able to predict the overall palatability of
      the total enteral nutrients with high accuracy. The products could be classified
      into three groups (peptide-based, amino-acid-based, and protein-based) by
      principal component analysis using sensor output of 8 channels. The products
      could be also classified into four groups; peptide-based, amino-acid-based, and
      protein-based and flavor addition group by principal component analysis using
      sensor output of channels 1, 3, 4 and 7, which are specific to basic tastes. The
      taste sensor could therefore be useful in predicting the taste or palatability of
      total enteral nutrients, and could contribute to attempts to improve compliance
      for such products and for enteral nutrients.

PMID- 15577237
TI  - Nucleosides XI. Synthesis and antiviral evaluation of 5'-alkylthio-5'-deoxy
      quinazolinone nucleoside derivatives as S-adenosyl-L-homocysteine analogs.
AB  - 4-amino-1-(beta-D-ribofuranosyl)quinazolin-2-one (3) was prepared by a direct
      glycosylation of 4-aminoquinazolin-2-one (7) using the Vorbruggen's silylation
      method and provided exclusively the beta-anomer. This quinazoline nucleoside and
      its 2',3'-O-isopropylidene derivative (9) did not undergo the coupling reaction
      with dialkyl disulfides in the presence of tri-n-butylphosphine unless their 4
      amino groups were protected by N,N-dimethylaminomethylidene. This approach
      provides a viable alternative synthetic route to 5'-alkylthio-5'-deoxy
      nucleosides.

PMID- 15577238
TI  - Application of revised version of neural independent component analysis to
      classification problems of confiscated methamphetamine.
AB  - Recently, profiling the chemical substances in illegally distributed drugs has
      been needed in order to reveal the drug channels. However, this kind of profiling
      is often difficult because such drugs contain various kinds of impurities and the
      quantity of these impurities changes. Due to these circumstances, several
      methods, including a slightly revised ICA (Independent Component Analysis) by a
      Hebbian learning artificial neural network, were applied for profiling illegally
      distributed methamphetamine. Eventually, better classification results with the
      ICA than with other methods were obtained. These results show that ICA could make
      it easier to profile illegally distributed methamphetamine.

PMID- 15577239
TI  - Production of an antiproliferative furanoheliangolide by Lychnophora ericoides
      cell culture.
AB  - This work reports for the first time the production a furanoheliangolide
      (goyazensolide) by plant cell culture. Monitoring of the goyazensolide metabolism
      revealed that the maximum production occurred during the lag phase of the
      Lychnophora ericoides callus culture. The antiproliferative activity of obtained
      goyazensolide was evaluated against seven cancer cell lines using MTT assay. The
      results revealed a potent cytotoxic activity for the furaheliangolide with IC50
      values in the range of 0.06 microg/ml for CEM leukemia cells to 0.75 microg/ml
      for B16 melanome cells.

PMID- 15577240
TI  - Synthesis and in vitro antioxidant activity of glycyrrhetinic acid derivatives
      tested with the cytochrome P450/NADPH system.
AB  - Five glycyrrhetinic acid (Ib) derivatives have been synthesized to try to improve
      the antioxidant activity. Their in vitro antioxidant activities were studied
      using a cytochrome P450/NADPH reductase system from rat liver microsomes. The
      generation of microsomal free radicals was followed by oxidation of the DCFH-DA
      probe, while evaluating the capacity to inhibit reactive oxygen species (ROS)
      formation. Two hydroxylated derivatives, 18beta-olean-12-ene-3beta,11alpha,30
      triol (II) and 18beta-olean-12-ene-3beta,11beta,30-triol (IV), exhibited strong
      antioxidant activities. At a concentration of 1.0 mg/ml, these derivatives
      inhibited ROS formation by 50% and 51%, respectively. Moreover, two homo- and
      heterocyclic diene derivatives, 18beta-olean-11,13(18)-diene-3beta,30-diol (III)
      and 18beta-olean-9(11),12-diene-3beta,30-diol (V), were also effective in ROS
      scavenging activity (inhibition of 41% and 44% of ROS activity, respectively). In
      the same conditions, the lead compound (Ib) and the reference vitamin E inhibited
      ROS activity by 31% and 32%, respectively. Our results suggest that the chemical
      reduction of the 11-keto and 30-carboxyl groups into hydroxyl function (example,
      II, IV) can increase the antioxidant activity of Ib significantly. In view of
      these results, our study represents a further approach to the development of
      potential therapeutic agents from Ib derivatives for use in pathologic events in
      which, free radical damage could be involved.

PMID- 15577241
TI  - Novel dammarane-type glycosides from Gynostemma pentaphyllum.
AB  - Three new dammarane glycosides (1-3), together with five known compounds,
      gypenoside LXIX (4), gylongiposide I (5), gypenoside XLVIII (6), allantion (7)
      and vitexin (8) were isolated from the MeOH extract of the aerial parts of
      Gynostemma pentaphyllum. Compounds 5, 7, and 8 were isolated from this plant for
      the first time. Their structures were elucidated by 1D and 2D NMR spectra
      interpretation as well as by chemical degradation.

PMID- 15577242
TI  - Preparation of axially chiral biphenyl diphosphine ligands and their application
      in asymmetric hydrogenation.
AB  - Axially chiral biphenyldiphosphine ligands bearing diphenylphosphino group(s)
      and/or dicyclohexylphosphino group(s) were prepared in enantiomerically pure form
      starting from 2,6-dimethylnitrobenzene via 8 steps: iodination, reduction,
      methoxylation through diazotization, Ullmann coupling, bromination,
      phosphorylation, optical resolution, and silane reduction, and the obtained
      ligands were used in rhodium-catalyzed asymmetric hydrogenation.

PMID- 15577243
TI  - Quantitative determination of amorphous nicardipine hydrochloride in long acting
      formula (NIC-LA) using light anhydrous silicic acid.
AB  - We investigated a method to quantitatively determine amorphous nicardipine
      hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared
      using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose
      (CMEC). Consequently, since the quantity of total NIC in the formula can be
      determined by means of HPLC and crystal NIC can be determined by the differential
      scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC
      is constant and unaffected by excipients, we developed the HPLC-DSC method by
      which the quantity of amorphous NIC is calculated as the difference between the
      quantity of total NIC determined by HPLC and the quantity of crystal NIC
      determined by DSC. This practical HPLC-DSC method was confirmed to have good
      accuracy and reproducibility.

PMID- 15577245
TI  - Triterpenic derivatives of Achillea alexandri-regis BORNM. & RUDSKI.
AB  - Investigation of the aerial parts of Achillea alexandri-regis led to the
      identification of 19 chemical constituents: twelve 3-O-fatty acid esters of
      triterpene alcohols arnidiol (1-4), maniladiol (5-8) and 16beta-hydroxylupeol (9
      12), alpha-amyrin, beta-amyrin, beta-sitosterol, 3,4-O-dicaffeoyl quinic acid,
      cinnamic acid, pinoresinol-beta-D-glucoside and rutin. Among them, compounds 3,
      4, 8, 11 and 12 are new natural products. The structures of all compounds have
      been elucidated on the basis of their spectral and chemical data.

PMID- 15577244
TI  - Tyrosinase inhibitors from Rhododendron collettianum and their structure-activity
      relationship (SAR) studies.
AB  - A new coumarinolignoid 8'-epi-cleomiscosin A (1) together with the new glycoside
      8-O-beta-D-glucopyranosyl-6-hydroxy-2-methyl-4H-1-benzopyrane-4-one (2) have been
      isolated from the aerial parts of Rhododendron collettianum and their structures
      determined on the basis of spectroscopic evidences. Tyrosinase inhibition study
      of these compounds and their structure-activity relationship (SAR) were also
      investigated. The compounds exhibited potent to mild inhibition activity against
      the enzyme. Especially, the compound 1 showed strong inhibition (IC50=1.33
      microM) against the enzyme tyrosinase, as compared to the standard tyrosinase
      inhibitors kojic acid (IC50=16.67 microM) and L-mimosine (IC50=3.68 microM),
      indicating its potential used for the treatment of hyperpigmentation associated
      with the high production of melanocytes.

PMID- 15577246
TI  - Matrix metalloproteinase-1 inhibitor from the stem bark of Styrax japonica S. et
      Z.
AB  - A bioassay-guided fractionation of the ethyl acetate soluble fraction from the
      stem bark of Styrax japonica S. et Z. (Styracaceae) yielded two new lignan
      compounds, styraxjaponoside A (1) and styraxjaponoside B (2), along with three
      known compounds, matairesinoside (3), egonol glucoside (4), and
      dihydrodehydrodiconiferyl alcohol 9'-O-glucoside (5). The structures of compounds
      1-5 were determined by spectroscopic method, as well as 1D- and 2D-NMR (HSQC, 1H
      1H COSY, and HMBC) spectroscopy. Among them, compound 2 exhibited potent
      inhibitory activity against matrix metalloproteinase (MMP)-1, and prevented the
      UV-induced changes in the MMP-1 expression. In addition, compounds 3 and 5 were
      isolated from this plant for the first time.

PMID- 15577247
TI  - Tosylation of endocrine-disruptive alkylphenolic compounds in a solid-phase
      reaction system consisting of C18-modified silica gel and aqueous buffer
      solution.
AB  - The tosylation reaction of endocrine-disruptive alkylphenolic compounds in a
      solid-phase aqueous system was investigated with the aim of developing an
      environment-friendly and efficient derivatization method for HPLC analyses of
      environmental samples. The phenols were rapidly and efficiently converted to the
      tosyl derivatives on a commercially available ODS solid-phase cartridge by
      passing an aqueous buffer solution through it. The solid-phase aqueous tosylation
      system has been incorporated into a preconcentration step performed by solid
      phase extraction from environmental water.

PMID- 15577248
TI  - Spectrophotometric determination of hydroxylamine and its derivatives in
      pharmaceuticals.
AB  - A sensitive spectrophotometric method for the determination of hydroxylamine is
      described. The method is based on the oxidation of hydroxylamine to nitrite using
      sodium arsenate under alkaline condition. The formed nitrite is determined based
      on the diazo coupling reaction between p-nitroaniline and N-(1
      naphthyl)ethylenediamine dihydrochloride [NEDA]. The system obeys Beer's law over
      the concentration range 0-7 microg of hydroxylamine at 545 nm and the colour is
      stable for 3 h. The molar absorptivity of the colour system is found to be 6.7 x
      10(4) l mol(-1) cm(-1). The relative standard deviation is 1.2% for ten
      determinations at 4 microg of hydroxylamine. Interferences due to various foreign
      ions have been studied and the method has been applied to the determination of
      hydroxylamine and its derivatives used in pharmaceutical formulations after
      hydrolysis.

PMID- 15577249
TI  - Study on the chemical constituents of the South China Sea gorgonian Junceella
      juncea.
AB  - A new steroidal glycoside--4'-O-acetyl-3-O-[beta-D-arabino-pyranosyl-oxy]-cholest
      5-ene-3beta,19-diol (1), and a new glycerol derivative--1,2-O-[2'
      hydroxyoctadecyl]-glycerol (2), along with 16 known compounds were isolated from
      the EtOH/CH2Cl2 extracts of the South China Sea gorgonian coral Junceella juncea.
      The structures of 1 and 2 were established by extensive spectroscopic analysis,
      including 1D and 2D NMR data.

PMID- 15577250
TI  - Synthesis and biological evaluation of peptide mimics derived from first
      extracellular loop of CCR5 toward HIV-1.
AB  - Peptide mimics derived from the first extracellular loop of CCR5 bearing non
      peptide spacers in place of Ala-Ala-Ala sequence in the peptide moiety were
      synthesized, and the effects of these compounds on the inhibition against HIV-1
      were examined. Compound 2b having m-aminophenoxyacetic acid derivative as a non
      peptide spacer significantly inhibited HIV-1.

PMID- 15577251
TI  - Two new lactones and one new aryl-8-oxa-bicyclo[3,2,1]oct-3-en-2-one from
      Descurainia sophia.
AB  - Two new lactones (1, 2), descurainolide A and B, and one new aryl-8-oxa
      bicyclo[3,2,1]-oct-3-en-2-one (3), descurainin, together with five known
      compounds (4-8), were isolated from the seeds of Descurainia sophia (L.) WEBB ex
      PRANTL. The structures of the new compounds were elucidated by extensive studies
      of their 1D, 2D NMR and HR-MS. Compounds 4 and 5 showed cytotoxicity.

PMID- 15577252
TI  - A new cytotoxic naphthoquinone from Paepalanthus latipes.
AB  - Quinones constitute an important class of naturally occurring compounds. They are
      found in plants, fungi and bacteria. Large number of quinones has been associated
      with antitumor, antibacterial, antimalarial and antifungal activities. In this
      work we describe the isolation, structure determination and the cytotoxic index
      of a new 1,4-naphthoquinone isolated from the capitula of Paepalanthus latipes.

PMID- 15577253
TI  - Koboquinone A and B, new metabolites of kobophenol a in rats.
AB  - Two new phase I metabolites of phytoestrogen kobophenol A (1), called koboquinone
      A (2) and B (3), have been isolated from the feces of rats orally administered 1.
      Their structures were determined by spectroscopic methods. 2 also showed activity
      of stimulating the proliferation of cultured osteoblasts.

PMID- 15577254
TI  - New norditerpenoids with trypanocidal activity from Vitex trifolia.
AB  - Trypanocidal constituents of the fruits of Vitex trifolia were investigated.
      Activity-guided isolation of the acetone extract resulted in the isolation of two
      new norditerpene aldehydes, 1 and 2, together with five known diterpenes:
      vitexifolin E (3), vitexifolin F (4), vitexilactone (5), 6-acetoxy-9-hydroxy
      13(14)-labden-16,15-olide (6), and previtexilactone (7). In vitro minimum lethal
      concentrations of the isolated compounds against epimastigotes of Trypanosoma
      cruzi were 11 microM (1), 36 microM (2), 34 microM (3), 34 microM (4), 66 microM
      (5), 66 microM (6), and >265 microM (7).

PMID- 15577255
TI  - New sesquiterpene hydroperoxides with trypanocidal activity from Pogostemon
      cablin.
AB  - Trypanocidal constituents of Pogostemon cablin were investigated. Activity guided
      isolation of the acetone extract resulted in isolation of three new sesquiterpene
      hydroperoxides 1-3, together with a known sesquiterpene, patchouli alcohol (4).
      In vitro minimum lethal concentrations of the hydroperoxides 1-3 against
      epimastigotes of Trypanosoma cruzi were 0.84 microM (1), 1.7 microM (2) and 1.7
      microM (3). The activity of the corresponding alcohols and patchouli alcohol was
      very weak (MLC>200 microM).

PMID- 15577256
TI  - Neoclerodanes from Teucrium orientale.
AB  - Two new neoclerodane diterpenoids, 6-deacetyl-teucrolivin A (5) and 8beta-hydroxy
      teucrolivin B (6), were isolated from the aerial parts of Teucrium orientale,
      along with four already known neoclerodane diterpenoids, teucrolivin A (1),
      teucrolivin B (2), teucrolivin C (3) and teucrolivin H (4), previously isolated
      from Teucrium oliverianum. Their structures were elucidated on the basis of
      spectroscopic evidence and chemical transformations. Compounds 1-3 were assayed
      for antifeedant activity against Spodoptera littoralis, S. frugiperda and
      Heliocoverpa armigera. Teucrolivin A was the most potent of the three compounds
      tested.

PMID- 15577257
TI  - Phenolic glycosides from the stem bark of Albizzia julibrissin.
AB  - From the stem bark of Albizzia julibrissin DURAZZ (Leguminosae), two new phenolic
      glycosides (albibrissinosides A and B) were isolated. Their structures were
      determined by spectroscopic analysis. The albibrissinoside B was found to be a
      radical scavenger on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.

PMID- 15577258
TI  - Briarane diterpenoids from the formosan gorgonian Coral Junceella fragilis.
AB  - A new trihydroxy briarane-related diterpenoid, junceellolide I (1), along with a
      known metabolite, (1R,2R,5Z,7R,8S,9R,10R,12R,14R,17S)-2,14-diacetoxy-8,17-epoxy
      9,12-dihydroxybriara-5,11(20)-dien-19-one (2), have been isolated from the
      gorgonian coral Junceella fragilis, collected off the southern Taiwan coast. The
      structure, including the relative configuration of the new compound 1, was
      elucidated by the combination of spectral data, particularly in high-resolution
      1H- and 13C-NMR spectroscopy utilizing COSY, HMBC, HMQC, and NOESY experiments.

PMID- 15577259
TI  - Clove oil prevents glycyrrhizin gel formation in aqueous solution.
AB  - One persistent problem with using therapeutic concentrations of glycyrrhizin (GZ)
      is that, at these high concentrations, it forms a gel in an aqueous solution. We
      previously solved this problem by dissolving GZ in a highly concentrated
      phosphate buffer. Unfortunately, the resulting GZ solution has a hyperosmotic
      pressure that renders it unsuitable for use in patients. The aim of this study
      was to prepare a highly concentrated GZ solution having an osmotic pressure ratio
      of 1 and a pH of 7.4. By adding small amounts of oil and using a 100 mM phosphate
      buffer, we achieved an emulsified GZ solution that is stable at room temperature
      and has a physiological osmotic pressure and pH. When clove oil was used as an
      emulsifier, the gel formation temperature of GZ solution decreased appreciably
      compared to that of GZ solution without clove oil. Using scanning electron
      microscopy (SEM), we examined the detailed characteristics of GZ gels prepared
      from solutions with or without clove oil. SEM of cross sections of GZ gels
      revealed an irregular structure in gels prepared with clove oil, indicating that
      clove oil prevented the formation of the intermolecular GZ networks typically
      characterized by gels derived from pure GZ solutions.

PMID- 15577260
TI  - [New aspects of hexobarbital metabolism: stereoselective metabolism, new
      metabolic pathway via GSH conjugation, and 3-hydroxyhexobarbital dehydrogenases].
AB  - Hexobarbital, a short-acting hypnotic, is metabolized to 3'-hydroxyhexobarbital
      by cytochrome P450, and then to 3'-oxohexobarbital by liver cytosolic
      dehydrogenase. New methods of separation for hexobarbital and its metabolites by
      TLC have been developed and applied to study the metabolism of hexobarbital
      enantiomers and stereoselective metabolism of hexobarbital. (+)-Hexobarbital
      preferentially was transformed into beta-3'-hydroxyhexobarbital and the (-)
      enantiomer preferentially transformed into alpha-3'-hydroxyhexobarbital by rat
      liver microsomes. Glucuronidation and dehydrogenation of 3'-hydroxyhexobarbital
      were also stereoselective and the S-configuration at the 3'-position was
      preferred. Alpha-3'-hydroxyhexobarbital from (-)-hexobarbital and the beta-isomer
      from (+)-hexobarbital were shown to be preferentially conjugated with glucuronic
      acid in rabbit urine, and to be preferentially dehydrogenated to form 3'
      oxohexobarbital by rabbit and guinea pig 3-hydroxyhexobarbital dehydrogenases. A
      new metabolic pathway of hexobarbital was found in which 3'-oxohexobarbital
      reacts with glutathione to form 1,5-dimethylbarbituric acid and a cyclohexenone
      glutathione adduct, a novel metabolite. 1,5-dimethylbarbituric acid was excreted
      into the urine and the cyclohexenone-glutathione adduct into the bile of rats
      dosed with hexobarbital. 3-hydroxyhexobarbital dehydrogenases that dehydrogenate
      3-hydroxyhexobarbital into 3'-oxohexobarbital were purified from the liver
      cytosol of rabbits, guinea pigs, goats, rats, mice, hamsters, and humans and
      characterized. These enzymes were monomeric proteins and had molecular weights of
      about 34500-42000, and used NAD(+) and NADP(+) as cofactors, except for the human
      enzyme that had a molecular weight of about 58000 and used NAD(+) alone. Each
      enzyme exhibited its own characteristics. Substrate specificity demonstrated that
      3-hydroxyhexobarbital dehydrogenases dehydrogenate not only alpha,beta
      unsaturated cyclic and acyclic secondary alcohols but also some 17 beta-, 3 alpha
      hydroxysteroids or both, except for the human enzyme. The amino acid sequence of
      the hamster enzyme indicated that it belongs to the aldo-keto reductase
      superfamily and hydroxysteroid dehydrogenase subfamily.

PMID- 15577261
TI  - [Development research on oxidase functional model iron complexes].
AB  - This paper describes research performed in the Laboratory of Organic Chemistry,
      Showa Pharmaceutical University. Oxidation reactions involving the oxidase can be
      divided roughly into two kinds of reactions: The first involves electron removal
      from an aromatic ring or an active CH-bond. The other reaction involves hydrogen
      abstraction from an inactive CH-bond. The oxidase models, Fe(DMF)(3)Cl(2)(1+) and
      Fe(AN)(6)(3+)/AN, which we have synthesized, have been shown to work by the
      former mechanism, and the models Fe(AN)(6)(3+)-IO(4)(-)/AN, Fe(AN)(6)(2+)-Ac(2)O
      H(2)O(2)/AN, Fe(AN)(6)(2+)-2PAH-5Py-Ac(2)O-H(2)O(2)/AN, Fe(PA)(3)(OH(2))
      H(2)O(2)/AN and Fe(PA)(3)(OH(2))-O(2)-electrolysis/AN do so by the latter
      mechanism. Further, we found some iron (II or III)picolinate-H(2)O(2)/AN
      complexes have the 7 alpha-hydroxylase-like activity.

PMID- 15577262
TI  - [Identification of muscle-type carnitine palmitoyltransferase I and
      characterization of its gene structure].
AB  - To characterize energy metabolism in brown adipose tissue (BAT), differential
      screening of a cDNA library of rat BAT with a cDNA probe of rat white adipose
      tissue was carried out. We isolated one novel cDNA clone encoding a protein of
      88.2 kDa consisting of 772 amino acids. The deduced amino acid sequence showed
      the highest homology (62.6%) with that of rat liver carnitine
      palmitoyltransferase I (CPTI). The transcript corresponding to this cDNA was
      abundantly expressed not only in BAT but also in the heart and skeletal muscle.
      CPTI is a protein necessary for the beta-oxidation of long-chain fatty acids in
      mammalian mitochondria, and it has been suggested that at least two isoforms, the
      liver type and muscle (M-CPTI) type, exist. Based on these observations, we
      concluded that the novel cDNA clone isolated from rat BAT encodes M-CPTI.
      Isolation and characterization of a genomic DNA clone revealed that the gene for
      human M-CPTI consists of two 5'-noncoding exons, 18 coding exons, and one 3'
      noncoding exon spanning approximately 10 kbp, and a gene encoding
      choline/ethanolamine kinase-beta (CK/EK-beta) was located about 300 bp upstream
      from the M-CPTI gene with the same strand direction. Furthermore, we found
      atypical transcripts containing exons of both CK/EK-beta and M-CPTI genes in
      humans and rodents. The physiologic role(s) of these transcripts is still
      unknown. However, it is interesting that such transcripts are produced from two
      tightly arranged and functionally unrelated genes in mammalian tissues.

PMID- 15577263
TI  - [Pharmaceutical application of cyclodextrins as multi-functional drug carriers].
AB  - Owing to the increasingly globalized nature of the cyclodextrin (CyD)-related
      science and technology, development of the CyD-based pharmaceutical formulation
      is rapidly progressing. The pharmaceutically useful CyDs are classified into
      hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional
      characteristics and bioadaptability, these CyDs are capable of alleviating the
      undesirable properties of drug molecules through the formation of inclusion
      complexes or the form of CyD/drug conjugates. This review outlines the current
      application of CyDs in drug delivery and pharmaceutical formulation, focusing on
      the following evidences. 1) The hydrophilic CyDs enhance the rate and extent of
      bioavailability of poorly water-soluble drugs. 2) The amorphous CyDs such as 2
      hydroxypropyl-beta-CyD are useful for inhibition of polymorphic transition and
      crystallization rates of drugs during storage. 3) The delayed release formulation
      can be obtained by the use of enteric type CyDs such as O-carboxymethyl-O-ethyl
      beta-CyD. 4) The hydrophobic CyDs are useful for modification of the release site
      and/or time profile of water-soluble drugs with prolonged therapeutic effects. 5)
      The branched CyDs are particularly effective in inhibiting the adsorption to
      hydrophobic surface of containers and aggregation of polypeptide and protein
      drugs. 6) The combined use of different CyDs and/or pharmaceutical additives can
      serve as more functional drug carriers, improving efficacy and reducing side
      effects. 7) The CyD/drug conjugates may provide a versatile means for the
      constructions of not only colonic delivery system but also site-specific drug
      release system, including gene delivery. On the basis of the above-mentioned
      knowledge, the advantages and limitations of CyDs in the design of advanced
      dosage forms will be discussed.

PMID- 15577264
TI  - [Biological significance of lipid hydroperoxide and its reducing enzyme,
      phospholipid hydroperoxide glutathione peroxidase, in mammalian cells].
AB  - Excessive production of reactive oxygen species (ROS) may lead to oxidative
      stress, loss of cell function, and cell death by apoptosis or necrosis. Recently,
      ROS have gained attention as important second messengers. ROS lifetimes can be
      very short, and many types of ROS cannot penetrate organelle membranes. It is
      therefore thought that only ROS signal molecules that are generated locally in an
      organelle are transduced when cells are stimulated. Lipid hydroperoxides are one
      type of ROS of which the biological function has not yet been clarified. The
      phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) is a unique
      antioxidant enzyme and separately distributed to the mitochondria, nucleus,
      nucleoli, and cytosol, where it regulates phospholipid hydroperoxide and fatty
      acid hydroperoxide as signal molecules. This review focuses on the structure and
      biological functions of PHGPx in mammalian cells. Overexpression of different
      types of PHGPx in the RBL2H3 cell line provides a useful model system with which
      to clarify the ability of different types of PHGPx to modulate cellular function
      and the importance of lipid hydroperoxides as signal molecules. Transformant
      studies show that lipid hydroperoxide is an activator of lipoxygenase and
      cyclooxygenase and participates in inflammation, cardiolipin hydroperoxide is the
      signal molecule for the release of cytochrome c during apoptotic cell death, and
      PHGPx is a signal regulator in the IgE receptor-mediated signaling pathway. It is
      becoming clear that PHGPx has an important role in spermatogenesis, sperm
      function, and embryonic development, and its deficiency is implicated in human
      infertility and in embryonic lethality of PHGPx knockout mice.

PMID- 15577265
TI  - [Regulatory mechanisms of intracellular distribution of Na+-dependent glucose
      transporter and the role in recovery from cellular injury].
AB  - Exposure of cells or organs to sublethal stress induces the expression of some
      heat-shock proteins (Hsp), including Hsp70. In porcine renal LLC-PK(1) cells,
      heat stress (HS) elevates Hsp70 expression and Na(+)-dependent glucose transport.
      We examined whether Na(+)-dependent glucose transporter (SGLT1) interacts with
      Hsp70 to elevate SGLT1 activity and whether SGLT1 activation is involved in the
      recovery from HS injury. HS (42 degrees C for 3 h) elevated SGLT1 activity and
      expression of SGLT1 in the apical membrane fraction. HS increased the maximal
      transport rate (V(max)), but did not affect the apparent affinity constant (K(m))
      for glucose. The HS-induced SGLT1 activation was inhibited by anti-transforming
      growth factor (TGF)-beta1 antibody. Furthermore, transfection of anti-Hsp70
      antibody into the cells inhibited SGLT1 activation. These results suggest that HS
      induces TGF-beta1 secretion, and then Hsp70 forms a complex with SGLT1 and
      increases the distribution of SGLT1 in the apical membrane. Next, we examined the
      effect of HS on plasma membrane integrity. Accumulation of calcein, a membrane
      impermeable fluorescent dye, was decreased by HS and then returned to basal
      level. This recovery was inhibited by phloridzin, a selective SGLT inhibitor, and
      nonmetabolizable glucose analogues. Anti-TGF-beta1 antibody also inhibited the
      recovery of calcein accumulation. Taken together, the present results show that
      HS elevates SGLT1 activity mediated via the TGF-beta1 signaling pathway and that
      the increase in glucose uptake is necessary to repair plasma membrane injury.

PMID- 15577266
TI  - Development of an injectable formulation for the novel lipid A analog E5531 using
      a 'pH-jump method'.
AB  - In order to design an injectable formulation of E5531, a novel synthetic
      disaccharide analog of novel lipid A, for the treatment of septic shock, a 'pH
      jump method' was developed. In this method, E5531 was dispersed in 0.003 mol/l
      NaOH (pH 11.0, above pK(a2)) at 50 degrees C (above phase transition temperature)
      and then mixed with a buffer to neutralize the pH to 7.3. E5531 was dispersed as
      particles, and the size was approximately 20 nm. The structure of the particles
      was vesicular. After dispersal, the solution was sterilized using a filter,
      filled aseptically into vials, and lyophilized. The size of the particles did not
      change before and after lyophilization. The relationship between the
      physicochemical properties of the particles and the pharmacokinetics in rats
      after intravenous administration was investigated. The membrane fluidity of the
      particles was affected by the dispersal methods, the dispersal time in 0.003
      mol/l NaOH in the pH-jump method, and the addition of Ca(2+) to the solution. The
      membrane fluidity was correlated with the pharmacokinetics in rats.

PMID- 15577267
TI  - [Clinical pathway based on evidence-based medicine (EBM) for chemotherapy for
      lung cancer].
AB  - Recently, combination treatment with cisplatin has been recommended as
      chemotherapy for lung cancer. However, no clinical pathway for safe and efficient
      use of anticancer agents has been established. We devised a clinical pathway
      satisfying evidence-based medicine (EBM) criteria by analyzing case records and
      the relevant literature. We analyzed 73 case records of hospitalized patients who
      had undergone chemotherapy for lung cancer on the internal medicine ward of the
      Showa University Hospital. Grade 3 or higher toxicities of leukopenia,
      thrombocytopenia, anemia, vomiting, and diarrhea occurred in 30%, 51%, 14%, 5%,
      8%, and 1% of patients, respectively. Therefore the checklists for these
      toxicities were included in the clinical pathway. The National Cancer Institute
      Common Toxicity Criteria were used for the evaluation of toxicities. According to
      the guidelines of the American Society of Clinical Oncology and the US Infection
      Society, the indicated agents and criteria for their use were chosen for
      supportive cancer treatment. Pharmacists, physicians, and nurses collaborated in
      making the clinical pathway safe and sufficiently easy for practical use. The
      final version of the clinical pathway is compatible with EBM and includes items
      required for safe chemotherapy, which could be helpful in risk management.

PMID- 15577268
TI  - [Detection of bacteria contaminating blood for transfusion].
AB  - When Escherichia coli is cultured in nutrient broth at 1 x 10(3) cells/ml, 7.5 h
      are needed to detect cell growth as turbidity. The time to detect E. coli in this
      medium is reduced using the alamar blue method. Alamar blue is an oxidation
      reduction indicator that changes color in response to cell growth. E. coli can
      grow in nutrient broth containing red blood cells, but the detection of E. coli
      based on turbidity is difficult because the red blood cells muddy the medium. As
      the change in color in the alamar blue method is not affected by red blood cells,
      the growth of E. coli contaminating red blood cells is detectable. These results
      suggest that a cell growth indicator such as alamar blue is useful for the
      detection of bacteria contaminating blood for transfusion.

PMID- 15577269
TI  - [Randomized controlled study on the effectiveness of community pharmacists'
      advice for smoking cessation by Nicorette--evaluation at three months after
      initiation].
AB  - We conducted a randomized, controlled study to evaluate whether pharmacists'
      advice on smoking cessation would result in a higher smoking cessation rate using
      Nicorette (nicotine gum preparation). Fourteen pharmacies in Tokyo, Kanagawa, and
      Nagano participated. Smokers who visited pharmacies to buy Nicorette from March
      1, 2002, through August 31, 2002, were recruited and randomly assigned to two
      groups. For the intervention group (A), pharmacists provided both regular
      instructions on Nicorette use and smoking cessation advice at the first sale and
      then gave follow-up advice just before starting a cessation and 1, 3, and 8 weeks
      and 3 months thereafter. For the control group (B), pharmacists provided regular
      instructions alone. The primary outcome measure was the self-reported smoking
      cessation rate and the secondary outcome measure was the relationship between the
      smoker's egogram and effectiveness of intervention. Twenty-eight smokers were
      enrolled and randomized into group A (n=11) or group B (n=17). The absolute
      abstinence rate in groups A and B at 3 months was 45.5% and 31.2%, respectively.
      The odds ratio was 1.83, which was not statistically significant. There was no
      difference in egogram score between absolute abstinence subjects and
      nonabstinence subjects in group A. The egogram scores in Adapted Child of
      absolute abstinence subjects in group B were significantly higher than in
      nonabstinence subjects. In conclusion, instructions and advice given by
      pharmacists may improve the smoking cessation rate in smokers receiving nicotine
      replacement therapy.

PMID- 15577270
TI  - [Nationwide research on communication education curriculum in the faculty of
      pharmaceutical science. Second report: study of communication education
      curriculum before on-the-job training].
AB  - With the recent rapid shift in pharmaceutical education to the development of
      clinical experts, emphasis on education in humanism and communication has
      increased. However, there is a lack of experience in these fields of
      pharmaceutical education in Japan, and there have been few studies on the
      curriculum, from admission to the pharmaceutical science to the stage before on
      the-job training. Also our previous survey of communication-related education
      revealed there is no consensus on the interpretation of communication-related
      education. In this study, therefore, we investigated communication-related
      education is incorporated before on-the-job training at 46 schools of
      pharmaceutical science in Japan. Communication-related education was carried out
      at 26 (56.5%) of the 46 schools, and role-playing was incorporated in the program
      at 23 (88.5%) of these 26 schools. However, SP (simulated patient/standardized
      patient) was adopted at 12 (46.2%) of these 26 schools. There was a psychologist
      or a communication specialist on the staff at only 10 (38.5%) of these 26
      schools, revealing the lack of instructors in these fields. Interest in education
      related to communication was generally weak at national and public universities,
      and marked differences in the approach to pharmaceutical education among
      university types were observed. The preparation of basic guidelines and textbooks
      for stepwise communication education from lower to higher grades and the training
      of instructors are urgently needed.

PMID- 15577271
TI  - Impulsiveness, locus of control, motivation and problem gambling.
AB  - A questionnaire consisting of demographic items, questions about gambling
      behavior, the South Oaks Gambling Screen (SOGS), a depression inventory, the
      Eysenck Impulsiveness Questionnaire, Levenson's Internality, Powerful Others and
      Chance Scales of locus of control and the Gambling Motivation Scale, was
      completed by a non-random sample of 147 New Zealand university students who
      gambled for money, median age 24 years. Approximately 17 of the sample was
      classified as problem gamblers, the rest as non-problem gamblers. Multivariate
      analysis of variance showed that there were significant differences between
      problem and non-problem gamblers on gambling frequency, number of activities,
      parents' gambling, depression, impulsiveness and motivation, but not on locus of
      control. Amotivation (apathy) and motivation towards stimulation correlated with
      powerful others and chance locus of control, and motivation to impress others
      with powerful others locus of control. Hierarchical regression analysis showed
      that: (1) beyond gambling frequency, number of activities and parents' gambling,
      motivation explained a substantial proportion of variance in SOGS scores, with
      impulsiveness accounting for a lesser amount, and (2) predictors of problem
      gambling included impulsiveness, amotivation and the motivations for
      accomplishment and tension release. It was concluded that gambling motivation is
      a more useful construct than locus of control in explaining problem gambling.
      Suggestions were made for future research, and aspects of gambling motivation
      were discussed in terms of a treatment program with groups of problem gamblers.

PMID- 15577272
TI  - Evolutionary and cross-cultural perspectives on gambling.
AB  - Few attempts have been made to incorporate evolutionary and cross-cultural
      perspectives on gambling. This paper begins with the assumption that gambling
      represents a risky endeavor undertaken for the purpose of winning stakes. This
      assumption leads to the derivation from evolutionary theory of two hypotheses
      concerning the socio-demographic characteristics of gamblers: (1) gambling should
      be over-represented among males, and (2) among young adults. To test these
      hypotheses, data are drawn from three sources. A cross-cultural sample of 60
      societies reveals that males are more often identified as gamblers than females,
      and these results do not appear to reflect reporting biases. The data are
      insufficient to enable conclusions about age patterns associated with gambling
      within this cross-cultural sample. Nationally representative studies of problem
      and pathological gamblers drawn from seven nation states show that such gamblers
      tend to be over-represented by young males, as predicted. Lastly, available
      demographic data on casino gambling hint at sex differences in the games played
      and the stakes wagered, but require further research for robust conclusions to be
      drawn.

PMID- 15577273
TI  - Gambling participation and social support among older adults: a longitudinal
      community study.
AB  - The purpose of this preliminary study was to examine associations between leaving
      home to engage in bingo or gambling activity and indices of physical and mental
      health and social support among a representative community cohort of 1016 elderly
      people. Cross-sectional and longitudinal data gathered from a prospective
      epidemiological study in a rural, low socio-economic status, area of Pennsylvania
      was employed. The cohort had a mean age of 78.8 (SD = 5.1) (range 71-97) and
      participated in three consecutive biennial "waves" of data collection. Nearly
      half (47.7) of the cohort reported gambling. To predict gambling, the independent
      variables included age, sex, education, employment, social support, depressive
      symptoms, self-rated health, alcohol use, cigarette use, and cognitive
      functioning. In cross-sectional, univariate analyses, gambling was associated
      with younger age, sex (male), fewer years of education, greater social support,
      lower depression scores, better self-rated health, alcohol use in the past year,
      and higher cognitive functioning. In a cross-sectional multiple regression model,
      younger age, greater social support, and alcohol use in the past year remain
      strongly and independently associated with gambling activity. Longitudinally,
      age, sex, social support, alcohol use, and gambling are predictive of future
      gambling activity. The results revealed that gambling may offer a forum of social
      support to older adults who are often isolated as they age.

PMID- 15577274
TI  - Changes in suicide and divorce in new casino jurisdictions.
AB  - Using county-level data, this study examines the impact that the introduction of
      casino gambling has on suicide and divorce. Eight communities that adopted casino
      gambling between 1991 and 1994 are compared with a matched set of control
      counties, jurisdictions that are economically and demographically similar to the
      casino counties. Suicide rates are not statistically different between casino and
      control communities. Divorce rates are lower in three casinos counties, higher in
      one, and not statistically different in four. Overall, the results suggest no
      widespread, statistically significant increase in either suicide or divorce.
      Possible explanations for the results are provided.

PMID- 15577275
TI  - The relationship of ecological and geographic factors to gambling behavior and
      pathology.
AB  - The current study examined the effect of neighborhood disadvantage and gambling
      availability on gambling participation and pathology. A national telephone survey
      included 2631 US adults. Census data was used to characterize the respondent's
      neighborhood, and the distance from the respondent's home to gambling facilities
      was calculated. Logistic and linear regressions were performed to predict
      gambling participation and pathology. Results showed that the neighborhood
      disadvantage was positively related to frequency of gambling and
      problem/pathological gambling. The presence of a casino within 10 miles of the
      respondent's home was positively related to problem/pathological gambling. The
      permissiveness of gambling laws was positively related to any gambling in the
      past year, as well as frequent gambling. These results were interpreted to mean
      that the ecology of disadvantaged neighborhoods promotes gambling pathology, and
      that availability of gambling opportunities promotes gambling participation and
      pathology.

PMID- 15577276
TI  - A comparison of the sleep-wake patterns of cosleeping and solitary-sleeping
      infants.
AB  - This study examined whether 3-15, month-old cosleeping infants displayed
      differences in time spent in active versus quiet sleep, and in the
      number/duration of nighttime awakenings when compared with solitary-sleeping
      infants; and also whether they spent the majority of the night sleeping face-to
      face, as previously reported. Nine cosleeping and nine solitary-sleeping infants
      were matched on age, gender, ethnicity, maternal age, and family SES. Video
      recordings of nighttime sleep yielded percentage of time in active sleep, quiet
      sleep, and awake, number of wakenings, and the percentage of time cosleeping
      infants and mothers spent face-to-face. Across age, cosleeping infants had more
      awakenings per night mean 5.8(1.50) versus 3.2(1.95); t = 3.16, p = .006). The
      percent of the nighttime spent awake did not differ between groups, suggesting
      that cosleeping infants had shorter awakenings. Cosleeping infants spent 40% of
      the night face-to-face with their mothers.

PMID- 15577277
TI  - Further psychometric properties of the Tourette's Disorder Scale-Parent Rated
      version (TODS-PR).
AB  - This study evaluated the psychometric properties of the Tourette's Disorder Scale
      Parent Rated (TODS-PR), a 15-item parent-rated instrument that assesses a range
      of common symptoms seen in childhood Tourette's Disorder (TD) patients including
      tics, obsessions, compulsions, inattention, hyperactivity, aggression, and
      emotional disturbances. Participants were 67 children and adolescents ages 6-17
      years who were diagnosed with TD and/or OCD and seen as a part of a larger study.
      Confirmatory factor analyses supported the original 4-factor structure of the
      TODS-PR with some slight re-specification of factor content. Internal
      consistencies were acceptable for the TODS-PR Total Score and factors. The TODS
      PR Total Score and factors showed good convergent validity with other measures of
      symptomatology and impairment. These findings suggest that the TODS-PR is a
      reliable and valid parent-rating scale for assessing TD symptoms.

PMID- 15577278
TI  - Divorce and children's adjustment problems at home and school: the role of
      depressive/withdrawn parenting.
AB  - This study examined linkages between divorce, depressive/withdrawn parenting, and
      child adjustment problems at home and school. Middle class divorced single mother
      families (n = 35) and 2-parent families (n = 174) with a child in the fourth
      grade participated. Mothers and teachers completed yearly questionnaires and
      children were interviewed when they were in the fourth, fifth, and sixth grades.
      Structural equation modeling suggested that the association between divorce and
      child externalizing and internalizing behavior was partially mediated by
      depressive/withdrawn parenting when the children were in the fourth and fifth
      grades.

PMID- 15577279
TI  - Behavioral profiles in 4-5 year-old children: normal and pathological variants.
AB  - Normal and psychopathological patterns of behavior symptoms in pre-school
      children were described by a classification approach using cluster analysis. The
      behavior of 406 children, average age 4 years 9 months, from the general
      population was evaluated at home visits. Seven clusters were identified based on
      empirically defined dimensions: attention, hyperactivity, aggressiveness, social
      relationship problems, sleeping problems, eating problems, depression and
      anxiety. Clusters scoring high in inattention, hyperactivity, aggressiveness, and
      social relationship problems but low in depression and anxiety were found and
      could indicate early onset conduct disorder. The approach of analysing patterns
      of symptoms expands the basis on which normal and psychopathological patterns are
      distinguished.

PMID- 15577280
TI  - An ecological-transactional model of significant risk factors for child
      psychopathology in outer mongolia.
AB  - The present study examined significant risk factors, including child
      maltreatment, for child psychopathology in a cross-cultural setting. Ninety-nine
      Mongolian boys, ages 3-10 years, were assessed. Primary caregivers (PCG)
      completed structured interviews including the Emory Combined Rating Scale (ECRS)
      and the Mood and Feelings Questionnaire (MFQ). Structural equation modeling
      identifies eight risk factors affecting child psychopathology: Three with direct
      effects (severity of physical punishment, PCG's MFQ score, and PCG's education),
      three with indirect effects (cultural acceptance of violence as discipline,
      presence of community violence, and contact with extended family), and two with
      direct and indirect effects (quality of marriage/presence of spousal abuse, and
      household size). Results support the ecological-transactional theory of
      developmental psychopathology in a cross-cultural setting. Structural equation
      modeling provides a useful technique to isolate specific sites for intervention,
      while maintaining a comprehensive perspective of risk factor interaction.

PMID- 15577281
TI  - Don't you know me? Mutual recognition in a case of mistaken identity.
AB  - Contemporary relational theories in psychoanalysis recognize the fully two-person
      nature of the clinical process. Both patient and therapist bring to the encounter
      their internal worlds in equal measure, each exerting constant influence on the
      other, to create a highly complex relational field. From this perspective,
      clinical vignettes should provide the same level of description of the
      therapist's as of the patient's contributions to the treatment process. It is
      argued that the body of clinical relational literature, in general, has not kept
      up with its rich theoretical contributions. This case vignette and discussion,
      both in structure and content, is an in-depth illustration of the mutual
      construction of the clinical process. Clinical material is offered from an
      extended phase of analytic treatment during which the therapeutic relationship
      and so the patient's possibilities for growth and change shifted from seeming
      stasis and impasse into new realms of experience of self and others. The author's
      intent is to demonstrate with specificity the ways in which the experiential
      worlds of patient and therapist collide and influence each other to create the
      intersubjective field that is the locus of therapeutic action and analysis. The
      phase of work described in this paper was challenging and ultimately successful
      due both to the severe and pervasive nature of the patient's struggles along with
      his underlying courage to persevere in the face of them, and to the ways in which
      the therapist's life experiences and capacities inescapably contributed to the
      shape, limitations and possibilities of the therapeutic process.

PMID- 15577282
TI  - The predictive power of Horney's psychoanalytic approach: an empirical study.
AB  - This study investigated the construct validity of a measure of Karen Horney's
      (1945) psychoanalytic theory that postulated three neurotic trends: compliant,
      aggressive, and detached. Her theory was operationalized by the Horney-Coolidge
      Type Indicator (HCTI). One hundred seventy-two adults completed the HCTI and the
      short form of the Coolidge Axis II Inventory, a measure of the three DSM-IV
      personality disorder clusters. Multiple regression and canonical correlation
      analyses revealed significant and differential patterns of the three HCTI
      dimensions with the three clusters. Because Paris (1994) has noted that Horney's
      neurotic trends may today be conceived of as personality disorders, one
      implication of the present findings is that Horney's dynamic theory can be valid
      and useful in the general understanding of personality disorders from a cluster
      perspective.

PMID- 15577283
TI  - Projection, introjection, and projective identification: a reformulation.
AB  - In this essay, the author recommends a reformulation of the psychoanalytic
      concept of projection. The author proposes that projective processes are not
      merely defensive maneuvers that interfere with perception, but rather an
      essential means by which human perception is rendered possible. It is the manner
      in which human beings test and-evaluate reality in terms of their experiential
      structure, and their needs for survival and nourishment. Projection is the early
      phase of introjection.

PMID- 15577287
TI  - Dietary patterns and risk of colon cancer and adenoma in a cohort of men (United
      States).
AB  - BACKGROUND: Examining the effects of dietary patterns on cancer risk may provide
      insights beyond the assessment of individual foods or nutrients. DESIGN: In the
      health professionals follow-up cohort, associations between the 'prudent' and the
      'western' dietary pattern and risk of colon cancer and adenomas were examined in
      561 colon cancer cases and 1207 distal colon adenoma cases. RESULTS: Higher
      prudent pattern scores were only weakly and non-significantly associated with
      decreased risk of colon cancer or distal colon adenoma (highest versus lowest
      quintile: colon cancer: multivariate adjusted relative risk (RR) = 0.84 (95%
      confidence interval (CI) = 0.64-1.10); p(trend) = 0.37; distal adenoma:
      multivariate odds ratio (OR) = 0.88 (95% CI = 0.73-1.08); p(trend) = 0.12). Our
      findings suggest a moderately increased risk of colon cancer and distal adenoma
      with higher western pattern scores (colon cancer: RR = 1.27 (95% CI = 0.96-1.69),
      p(trend) = 0.05; distal adenoma: OR = 1.28 (95% CI = 1.05-1.56), p(trend) =
      0.01). Adding body mass index, which is positively related to western pattern and
      thus may be considered an intermediate endpoint between western pattern and colon
      cancer, attenuated associations somewhat but not substantially. CONCLUSION: Our
      data do not provide evidence for an appreciable inverse association between
      higher prudent pattern scores and risk of colon cancer or distal colon adenomas,
      but do support a moderate positive association between higher western pattern
      scores and risk of colon cancer or distal colon adenomas.

PMID- 15577288
TI  - Associations between BMI, energy intake, energy expenditure, VDR genotype and
      colon and rectal cancers (United States).
AB  - Components of energy balance are important elements associated with colorectal
      cancer risk. In this study we examine the association between VDR genotypes, BMI,
      physical activity, and energy intake and risk of colorectal cancer. Data from a
      population-based case-control study of colon (1174 cases and 1174 controls) and
      rectal (785 cases and 1000 controls) cancer was used to evaluate the
      associations. The Bsm1, polyA, and Fok1 VDR polymorphisms were evaluated. For
      colon cancer, those who are obese were at greater risk of colon cancer if they
      had the SS or BB (OR = 3.50; 95% CI = 1.75-7.03; p interaction 0.03) or ff (OR =
      2.62; 95% CI = 1.15-5.99; p interaction 0.12/) VDR genotypes. On the other hand,
      those who were least physically active were at greater risk of colon cancer if
      they had the ff VDR genotype (OR = 3.46; 95% CI = 1.58-7.58; p interaction 0.05).
      The association between energy intake and colon cancer appears to be driven more
      by energy intake than Bsm1 or polyA VDR genotypes, although there was a
      significant interaction between the Fok1 VDR polymorphism and energy intake and
      risk of both colon and rectal cancer (p interaction 0.01 for colon and 0.04 for
      rectal). These data suggest a relationship between VDR genotype and factors
      related to energy balance in modifying colorectal cancer risk.

PMID- 15577289
TI  - Diabetes status and post-load plasma glucose concentration in relation to site
      specific cancer mortality: findings from the original Whitehall study.
AB  - OBJECTIVE: While several studies have reported on the relation of diabetes status
      with pancreatic cancer risk, the predictive value of this disorder for other
      malignancies is unclear. METHODS: The Whitehall study, a 25 year follow-up for
      mortality experience of 18,006 men with data on post-challenge blood glucose and
      self-reported diabetes, allowed us to address these issues. RESULTS: There were
      2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was
      positively associated with mortality from carcinoma of the pancreas and liver,
      while the relationship with lung cancer was inverse, after controlling for a
      range of potential covariates and mediators which included obesity and
      socioeconomic position. After excluding deaths occurring in the first 10 years of
      follow-up to examine the effect of reverse causality, the magnitude of the
      relationships for carcinoma of the pancreas and lung was little altered, while
      for liver cancer it was markedly attenuated. CONCLUSIONS: In the present study,
      diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts
      with serially collected data on blood glucose and covariates are required to
      further examine this area.

PMID- 15577290
TI  - Variation in screening mammography and Papanicolaou smear by primary care
      physician specialty and gatekeeper plan (United States).
AB  - OBJECTIVE: To assess whether the specialty of a patient's primary care physician
      or being part of a gatekeeper plan influence breast and cervical cancer
      screening. METHODS: Cross-sectional study of women in a national sample. For
      mammography, we studied women aged 40 and above, and for Papanicolaou (Pap)
      smear, women aged 18-65 years. Screening mammography or Pap smear within the
      previous two years was measured by patient self-report. The key independent
      variables were primary care physician specialty and whether the patient had a
      gatekeeper. RESULTS: Among women seen by a family practice physician, there was a
      higher probability of being screened if the patient was part of a gatekeeper plan
      than if the patient was not part of a gatekeeper plan: mammography (OR = 1.35;
      95% CI = 1.20-1.52) and Pap smear (OR = 1.60; 95% CI = 1.34-1.91). Among women
      seen by an internal medicine physician, cancer screening did not vary
      significantly by gatekeeper status. CONCLUSIONS: The impact of gatekeeper plans
      upon cancer screening varies according to the primary care physician's specialty.
      Policy interventions designed to increase cancer screening should take into
      account different responses to gatekeeper requirements among different types of
      providers.

PMID- 15577291
TI  - Melanoma and lifetime UV radiation.
AB  - OBJECTIVE: Because most risk factors for melanoma are immutable constitutional
      factors such as skin type, it is important to more fully understand the
      relationship between melanoma risk and sun exposure, one of the few modifiable
      risk factors for the disease. The goal of this case-control study was to quantify
      the risks of melanoma associated with UV exposure at different periods of life.
      METHODS: Cases were 386 patients between the ages of 35 and 74 who were diagnosed
      with primary cutaneous melanoma within the Seattle-Puget Sound area during 1997.
      Controls were 727 participants of the same age and geographic area, selected by
      random-digit dialing. A telephone interview included a complete residential
      history, lifetime sun exposure history (days in the summer sun for at least 4 h
      at each place of residence), and personal characteristics. UV exposure was
      calculated based on satellite data on potential erythemal exposure at each place
      of residence, years at each location and time spent in the sun at each location.
      Logistic regression was used to estimate odds ratios (OR) and 95% confidence
      intervals (CI) reflecting the risk of melanoma associated with UV exposure, after
      adjustment for age, sex, income, tendency to burn and sunburns during ages 2-10.
      RESULTS: Among women, lifetime UV exposure was associated with melanoma risk
      (adjusted OR = 1.99 for highest versus lowest quartile, 95% CI: 0.95-3.03, p for
      trend = 0.008). There were significant trends for UV exposure during ages 1-10,
      11-20 and 31-40 (all p < 0.02). Among men, there were no significant associations
      at any time period, but lifetime UV exposure was associated with higher risk for
      men who had a tendency toward severe or painful sunburns (OR = 2.85 for highest
      versus lowest quartile, 95% CI: 0.84-9.64, p for trend = 0.04). CONCLUSION: The
      differing results by sex are not easily interpretable, though it may be useful to
      target those with a higher sensitivity to the sun when formulating messages for
      prevention of melanoma by lowering exposure to UV.

PMID- 15577292
TI  - Recent increase in cancer survival according to age: higher survival in all age
      groups, but widening age gradient.
AB  - A major increase in long-term survival of cancer patients in the 1990s has
      recently been demonstrated. It is unclear, however, to what extent this increase
      has been shared by cancer patients at various ages. Using the 1973-2000 data base
      of the Surveillance, Epidemiology, and End Results programme, recent increase in
      10-year relative survival of cancer patients in the US was assessed for 4 major
      age groups and 15 major cancer sites by comparing results of a period analysis
      for the 1996-2000 period with results of a cohort analysis for patients diagnosed
      in 1986-1990. Period estimates of 10-year relative survival for all forms of
      cancer combined in 1996-2000 were 66.1%, 58.8%, 56.3% and 47.1% for age groups 15
      54, 55-64, 65-74 and > or = 75 years, respectively. They were 7.4%, 10.4%, 7.8%
      and 3.0% units higher than the respective 1986-1990 cohort estimates for these
      age groups. The increase in 10-year relative survival strongly varied by cancer
      site, but it was generally less pronounced in older than in younger patients. We
      conclude that long-term survival expectations of cancer patients have increased
      in all age groups in the 1990s. However, for most common forms of cancer, the age
      gradient in survival has either persisted or widened.

PMID- 15577293
TI  - A prospective study of diet and prostate cancer in Japanese men.
AB  - BACKGROUND AND AIMS: It has been hypothesized that some aspect of a traditional
      'Asian' diet, that is low in animal products and high in soya, may be associated
      with a reduced risk of prostate cancer. This study aimed to examine the
      association between dietary intake and prostate cancer risk among 18,115 men in
      Hiroshima and Nagasaki, Japan, using prospective data from the Life Span Study.
      METHODS: Subjects completed a food-frequency questionnaire at baseline (1963,
      1965 and/or 1979) and were followed for incident prostate cancer until the end of
      1996. During this time, 196 incident prostate cancer cases were identified after
      252,602 person-years of observation. Poisson regression was used to calculate
      incidence rates for each dietary factor after adjustment for age, calendar
      period, city of residence, radiation dose and education level. RESULTS: Fish
      intake was significantly associated with an increased risk of prostate cancer;
      men who consumed fish more than four times per week had a 54 increased risk of
      developing prostate cancer compared with men who ate fish less than twice per
      week (RR = 1.54; 95% CI, 1.03-2.31). No other food items, including soya
      products, were significantly associated with prostate cancer risk. CONCLUSIONS:
      These data suggest that dietary factors may not be strong determinants of
      prostate cancer in these Japanese men, although the increased risk associated
      with a high consumption of fish warrants further study.

PMID- 15577294
TI  - Geographic clustering of residence in early life and subsequent risk of breast
      cancer (United States).
AB  - OBJECTIVE: This study focused on geographic clustering of breast cancer based on
      residence in early life and identified spatio-temporal clustering of cases and
      controls. METHODS: Data were drawn from the WEB study (Western New York Exposures
      and Breast Cancer Study), a population-based case-control study of incident,
      pathologically confirmed breast cancer (1996-2001) in Erie and Niagara counties.
      Controls were frequency-matched to cases on age, race, and county of residence.
      All cases and controls used in the study provided lifetime residential histories.
      The k-function difference between cases and controls was used to identify spatial
      clustering patterns of residence in early life. RESULTS: We found that the
      evidence for clustered residences at birth and at menarche was stronger than that
      for first birth or other time periods in adult life. Residences for pre
      menopausal cases were more clustered than for controls at the time of birth and
      menarche. We also identified the size and geographic location of birth and
      menarche clusters in the study area, and found increased breast cancer risk for
      pre-menopausal women whose residence was within the cluster compared to those
      living elsewhere at the time of birth. CONCLUSION: This study provides evidence
      that early environmental exposures may be related to breast cancer risk,
      especially for pre-menopausal women.

PMID- 15577295
TI  - Use of medication during pregnancy and risk of childhood leukemia (Canada).
AB  - OBJECTIVE: To examine risk of childhood acute lymphoblastic leukemia (ALL)
      associated with maternal use of medications during pregnancy; in particular
      medications known or suspected to be teratogenic. METHODS: Seven hundred and
      eighty nine children (< 15 years old) diagnosed with ALL in the province of
      Quebec between 1980 and 2000 were recruited for study. A similar number of
      population based controls matched to cases (1:1) by sex and age were chosen from
      family allowance or health insurance files. Information was gathered via
      telephone interview with the subjects' parents. Data were analyzed using
      conditional logistic regression. RESULTS: Risk of childhood ALL was significantly
      increased in the offspring of mothers who reported using any medication (adjusted
      odds ratio (OR(adj)) = 1.3, 95% CI = 1.0-1.6) or any teratogenic medication
      (OR(adj) = 1.4, 95% CI = 1.1-1.9) during pregnancy. Among specific medication
      categories, only central nervous system depressants were associated with a
      significantly increased risk, although elevated odd ratios were found for anti
      epileptics, immunosuppressants, oral contraceptives, and illicit drugs. Risk
      associated with use of teratogenic medications was higher with increased dose and
      in children diagnosed before two years of age. CONCLUSION: A modest increase in
      risk of ALL was found among children of mothers who used medication during
      pregnancy.

PMID- 15577296
TI  - Prostate cancer incidence and survival in relation to education (United States).
AB  - INTRODUCTION: There are few data on prostate cancer incidence and survival in
      relation to socioeconomic status in the 1990s, after the introduction of prostate
      specific Antigen (PSA) testing. MATERIALS AND METHODS: We studied the relation of
      education to prostate cancer incidence and survival in the Cancer Prevention
      Study II (CPS-II) Nutrition Cohort. Participants provided questionnaire data on
      diet, medical history, education, and PSA testing. We followed 72,449 men from
      1992-1999 for cancer incidence (4279 incident cases), and through 2000 for
      survival (158 prostate cancer deaths among incident cases). RESULTS: Multivariate
      adjusted rate ratios (RRs) were calculated using Cox proportional hazards models.
      Self-reported (PSA) tests were more common among the more highly educated. Men
      with at least a college education had a 15-19% higher prostate cancer incidence
      than those with a high school education or less, but this association was limited
      to localized cancers and was attenuated by adjustment for PSA testing. Survival
      analysis among incident prostate cancer cases adjusted for stage and grade at
      diagnosis showed much lower prostate cancer mortality for men with at least a
      high school education compared to those with less than a high school education
      (RR = 0.49, 95% CI = 0.32-0.76). CONCLUSIONS: This study suggests that higher
      education is associated with slightly increased incidence of prostate cancer, at
      least partly due to greater use of PSA screening and a greater detection of
      localized tumors among more highly educated men. The much lower survival rates
      from prostate cancer among those with less than a high school education cannot be
      explained by available data and may reflect disparities in treatment. In 1999,
      27% of US males over age 55 and older had less than a high school education.

PMID- 15577297
TI  - Life course breast cancer risk factors and adult breast density (United Kingdom).
AB  - OBJECTIVE: To determine whether risk factors in childhood and early adulthood
      affect later mammographic breast density. METHODS: Subjects were 628 women who
      attended a medical examination at the University of Glasgow Student Health
      Service (1948-1968), responded to a questionnaire (2001) and had a screening
      mammogram in Scotland (1989-2002). Mammograms (median age of 59 years) were
      classified using a six category classification (SCC) of breast density percent.
      Logistic regression was used to determine associations between risk factors and
      having a high-risk mammogram (>or = 25% dense). RESULTS: In multi-variable
      analyses, high-risk mammograms were associated with parity (adjusted odds ratio
      (OR) per child: 0.77 (95% confidence interval (CI) 0.61-0.99)), age at first
      birth, OR per year: 1.05 (0.99-1.11), smoking at university, OR smokers versus
      non-smokers: 0.58 (0.36-0.92) and body mass index (BMI) while at university, OR
      per 1 kg/m2 0.75 (0.69-0.82). No associations with SCC were found for age at
      menarche, birth weight, oral contraceptive (OC) use, height, leg length or
      exercise at age 20. CONCLUSIONS: We confirm previous findings that breast density
      is affected by reproductive events and some anthropometric measures, however most
      of the risk factors acting throughout the life course which we examined were not
      closely related to adult breast density.

PMID- 15577298
TI  - Familial aggregation of melanoma risks in a large population-based sample of
      melanoma cases.
AB  - OBJECTIVE: Melanoma has been shown in numerous studies to be associated with sun
      exposure, and with host phenotypic factors of genetic origin. In this study we
      use information from a large series of incident cases of melanoma from an
      international population-based study to examine the patterns of incidence of
      melanoma in the first-degree relatives of these cases. METHODS: A total of 2508
      incident cases of melanoma provided information on basic demographic data and
      pigmentary characteristics, in addition to detailed information on family history
      of melanoma. These data were used to examine the incidence rates ratios of
      melanoma in the relatives of cases in relation to population rates, and also with
      respect to phenotypic characteristics of the probands that have been shown to be
      associated with melanoma: mole counts, hair color, eye color, and skin
      sensitivity to the sun. RESULTS: The incidence rates reflect the underlying
      patterns of incidence in the source populations, with generally higher rates in
      the Australian sample, low rates in Italy, and intermediate rates in the USA and
      Canada. Also, rates are higher in men than in women, except at very young ages.
      Phenotypic characteristics of the probands were only weakly associated with the
      observed rates in the relatives although there is a strong inverse association
      with age at diagnosis. Cumulative risk of melanoma rises to 6.9% (6.1%) at age 80
      in male (female) first-degree relatives of cases, and to 10.8% (9.5%) in
      relatives of cases diagnosed before age 50. CONCLUSIONS: Relatives of cases
      diagnosed with melanoma are at considerable lifetime risk of the disease,
      especially if the case is diagnosed at a young age.

PMID- 15577299
TI  - Cancer patient survival in Sweden at the beginning of the third millennium-
      predictions using period analysis.
AB  - Estimates of cancer patient survival made using traditional, cohort-based,
      methods can be heavily influenced by the survival experience of patients
      diagnosed many years in the past and may not be particularly relevant to recently
      diagnosed patients. Period-based survival analysis has been shown to provide
      better predictions of survival for recently diagnosed patients and earlier
      detection of temporal trends in patient survival than cohort analysis. We aim to
      provide predictions of the long-term survival of recently diagnosed cancer
      patients using period analysis. The period estimates are compared with the latest
      available cohort-based estimates. Our results, based on period analysis for the
      years 2000-2002, suggest an improvement in survival for many forms of cancer
      during recent years. For all sites combined the 5-, 10-, 15-, and 20-year
      relative survival ratios were 62%, 53%, 48%, and 47% for males and 67%, 62%, 60%,
      and 59%, for females. These estimates were 3-14% units higher than those obtained
      using the latest available cohorts with the respective lengths of follow-up. The
      interval-specific relative survival stabilised for males at 97% after 8 years of
      follow-up and for females at 98% after 7 years for both period and cohort
      analyses.

PMID- 15577300
TI  - Chiari osteotomy in Legg-Calve-Perthes disease.
AB  - A retrospective study of 22 Chiari osteotomies in 21 children with severe Legg
      Calve-Perthes disease is presented. All cases were studied at skeletal maturity.
      The average age at surgery was 8.5 years with an average follow-up of 6.1 years.
      Four hips were classified as Catterall group III and the remaining hips as group
      IV. Arthrography was used preoperatively to measure the femoral head sphericity,
      the femoral head coverage and the eccentric index. The same parameters were
      studied on radiographs at skeletal maturity. Chiari osteotomy provided an
      improvement in the femoral head coverage and hip congruency. Radiographs showed
      progressive spherical remodelling of the femoral head and improvement of the
      concentricity. One hip required premature total hip replacement.

PMID- 15577301
TI  - How does a femoral varus osteotomy alter the natural evolution of Perthes'
      disease?
AB  - To study how a femoral osteotomy alters the natural evolution of Perthes'
      disease, records and radiographs of 640 patients with Perthes' disease were
      analyzed. The data of 314 patients who underwent femoral osteotomy were compared
      with those of non-operated patients. A new modification of classification of the
      stages of evolution of the disease was used to identify the timing of surgery and
      to monitor the progress of the disease following surgery. The duration of each
      stage of the disease, the extent of epiphyseal extrusion, the extent of widening
      of the femoral metaphysis and the dimensions of the acetabulum were noted on
      sequential radiographs. The changes in the femoral epiphysis and metaphysis and
      changes in the acetabulum were also noted. It was observed that a varus osteotomy
      clearly alters the natural evolution of Perthes' disease. Of patients who were
      operated in the stage of avascular necrosis, 34% bypassed the stage of
      fragmentation. The duration of the disease was shorter in these patients. The
      duration of the stage of fragmentation was reduced in operated children who
      passed through the stage of fragmentation. The extent of femoral head extrusion
      was minimized at the stage when it was most vulnerable for deformation.
      Metaphyseal widening and subsequent femoral head enlargement were also minimized
      in children who underwent a femoral osteotomy. The chances of retaining the
      sphericity of the femoral head were much higher in those children who had a
      femoral osteotomy. These beneficial effects of a varus osteotomy, were most
      evident when the operation was performed either in the stage of avascular
      necrosis or in the early stage of fragmentation.

PMID- 15577302
TI  - Usefulness of epiphyseal quotient measurement on magnetic resonance images for
      outcome prediction in patients with early-stage Legg-Calve-Perthes disease.
AB  - To investigate the usefulness of epiphyseal quotient (EQ) measurement for outcome
      prediction in patients with Legg-Calve-Perthes disease (LCPD), magnetic resonance
      (MR) imaging was performed in 26 patients with unilateral LCPD within 6 months of
      the disease onset and subsequently once every 3 months. All the patients were
      treated conservatively in our institute between 1990 and 1999. The mean follow-up
      period was 80 months. Clinical outcome was evaluated based on the plain
      radiograms of the femoral head at the final examination according to Stulberg's
      classification: the patients whose outcome was class I were regarded as
      'excellent' (excellent group), class II as 'good' (good group), and classes III,
      IV and V as 'poor' (poor group). The excellent group consisted of 10 patients,
      the good group of 12, and the poor group of four. The EQ measured on MR images
      (MR-EQ) decreased remarkably in the poor group chronologically, whereas there was
      no decrease in the excellent group and a slow decrease in the good group. The
      mean MR-EQ at or before the sixth month (range, 2-6 months; mean, 4.9 months) was
      86.2 (range, 76.8-94.8) in the excellent group, 78.3 (57.0-93.4) in the good
      group, and 67.4 (57.8-74.5) in the poor group (P<0.05 among the three groups).
      According to our results, because all patients having an MR-EQ at or before the
      sixth month of 75 or higher were classified in the excellent or good groups, it
      is thought that the ongoing method of treatment can be continued. On the other
      hand, since half of the patients having an MR-EQ at or before the sixth month of
      lower than 75 were classified in the poor group and had a high potential for a
      poor outcome, it is thought that these patients require strict containment
      therapy, and altering the surgical procedure could be considered depending on the
      particular patient. It was thought that the MR-EQ is a useful predictive factor
      of LCPD prognosis.

PMID- 15577303
TI  - Osteochondritis of the femoral condyles in children and adolescents: our
      experience over the last 28 years.
AB  - A study of 67 cases was carried out amongst children and adolescents suffering
      from osteochondritis of the femoral condyle (with open or closed knee physis).
      All attended our orthopaedic and traumatology centre over a 28-year period (1973
      2001). A total of 67 patients have been treated. Arthrotomy and drilling of the
      affected area was performed on 12 patients; 48 patients were treated with
      arthroscopic multiple-perforations of the affected articular cartilage and the
      remaining seven evolved correctly with conservative treatment. Our study has
      taken into account the symptomatology and the period of preoperative evolution,
      radiological forms of presentation and the state of the lesion. Follow-up has
      varied between 12 and 72 months, with an average of 39 months. Despite
      controversy regarding the usefulness of multiple perforations, we believe it to
      be the best method of treatment during childhood and adolescence, especially for
      patients with an open physis.

PMID- 15577304
TI  - Should full-length standing anteroposterior radiographs replace the scanogram for
      measurement of limb length discrepancy?
AB  - The orthoroentgenogram, commonly known as the 'scanogram', continues to be the
      most widely used imaging technique for measuring limb length discrepancy (LLD).
      This study reviews other methods of measuring LLD including full-length standing
      anteroposterior radiographs, computed tomography/digital localization image, and
      microdose digital scanography. We present seven cases that demonstrate the
      pitfalls of scanograms as compared with full-length standing anteroposterior
      radiographs. Illustrative cases provide the rationale for the clinician managing
      LLD on a regular basis to utilize full-length standing anteroposterior
      radiographs as the instrument that will provide the most clinically relevant
      information.

PMID- 15577305
TI  - The relation of joint laxity and trunk rotation.
AB  - A study was designed to evaluate the joint laxity during scoliosis screening, and
      to show if there is a relation of joint laxity values to the trunk rotation. One
      thousand, two hundred and seventy-three children (598 females, 675 males) with an
      average age of 10.4 years were screened with a scoliometer and forward bending
      for trunk rotations. Scapular and shoulder elevations, flexible pes planus were
      recorded and joint laxity was evaluated with the Beighton score. There was high
      inter-observer and intra-observer reliability for both scoliometer and Beighton
      scores. In 41 children (3.2%) with Beighton score 7 or higher, trunk rotation
      measurements were higher than for the rest of the children. Trunk rotation
      measurements of 7 degrees or higher were found in 30 children, who were more lax
      than the rest of the group and were invited for radiography, with a detection of
      curves between 11 and 18 degrees in 10 of them. The Beighton score is a practical
      and reliable method for defining joint laxity. Although the number of patients
      with scoliosis was limited, there are findings supporting the relation between
      joint laxity and scoliosis. Moreover, there was increased laxity in children with
      increased trunk rotations. Ligamentous laxity may be one of the causes changing
      the contour of the back.

PMID- 15577306
TI  - Carpal tunnel syndrome in children.
AB  - Carpal tunnel syndrome is a condition rarely encountered in infants. We describe
      five patients with nine involved hands. One was reported earlier. In three cases
      the cause of carpal tunnel syndrome is a storage disease: one girl with
      mucolipidosis type III and a boy and a girl with mucopolysaccharidosis type I.
      The fourth case is a girl presenting with unilateral macrodactyly of the right
      third and fourth digits. The last case involves a boy with familial carpal tunnel
      syndrome. We briefly discuss these patients and review the literature since 1989.

PMID- 15577307
TI  - Long-term follow-up of a malunited, isolated fracture of the capitate in a 6-year
      old boy.
AB  - A 6-year-old boy with an isolated fracture of the capitate was presented. First
      radiograghs at our clinic revealed an oblique fracture with a displacement of 5
      mm on the lateral view, which we successfully treated with immobilization. When
      complete union was recognized in the radiographs, the capitate had a deformity
      consisting of a large prominence on the palmar aspect. During follow-up, the
      capitate showed marked remodeling and at four and a half years after injury it
      had regained an almost normal shape. Eleven years after injury, there were no
      radiographic changes such as malalignment or arthrosis in the carpal bones.

PMID- 15577308
TI  - Ossifying subperiosteal hematoma associated with neurofibromatosis type 1.
      Diagnostic hesitation: a case report and literature review.
AB  - We here in report a case of ossifying subperiosteal hematoma in a child with
      Neurofibromatosis Type I. The availability of an MRI and centers experience with
      the disease supported our delay in aggressive treatment of this expanding
      inflammatory mass.

PMID- 15577309
TI  - Osteomyelitis of the rib due to Streptococcus pneumoniae: a very rare condition
      in children.
AB  - Rib osteomyelitis is a rare disease. We present a previously unreported case of
      Streptococcus pneumoniae osteomyelitis of the rib. A 4-month-old-infant presented
      with fever, irritability and abdominal tenderness. Pericostal collection was
      discovered incidentally on ultrasound; it was first drained by needle aspiration
      and appropriate antibiotic therapy was given, with resolution of fever in 24 h,
      but recurrence of symptoms 4 days later, with swelling over the affected rib.
      Surgical drainage with resection of the infected portion of the rib were done
      followed by a prolonged course of intravenous and then oral antibiotics, without
      any recurrence at 6 months follow-up. A review of the pertinent literature was
      made. This case demonstrates that the spectrum of pathogens potentially
      responsible for rib osteomyelitis may be broader than previously reported. The
      management and outcome are similar to rib osteomyelitis due to any other
      bacteria.

PMID- 15577311
TI  - Surgical technique for an 'almost' percutaneous triple pelvic osteotomy for
      femoral head coverage in children 6-14 years of age.

PMID- 15577312
TI  - A phase II study of bendamustine chemotherapy as second-line treatment in
      metastatic uveal melanoma.
AB  - Uveal melanoma is the most frequent primary malignant neoplasm of the eye and has
      a poor prognosis in metastatic stage. Fotemustine or a combination of gemcitabine
      and treosulfan has demonstrated some efficacy in metastatic disease. We conducted
      a phase II trial to assess the second-line activity and toxicity of bendamustine
      hydrochloride, a nucleoside analogue with alkylating activity. Inclusion criteria
      were a Karnofsky performance status of > or = 60% and progressive disease during
      or after first-line chemotherapy. Bendamustine was administered at a dose of 120
      mg/m2 on days 1 and 2. Cycles were repeated on day 22. The primary endpoint of
      the study was the determination of the number of patients achieving an objective
      response or stable disease. The secondary endpoint was toxicity. Eleven patients
      were enrolled into the trial. Grade III and IV toxicity consisted of anaemia,
      thrombocytopenia and leucocytopenia in two, one and two patients, respectively.
      No grade III or IV non-haematological toxicity was observed. According to
      Response Evaluation Criteria in Solid Tumours (RECIST), all patients showed
      progressive disease. We conclude that bendamustine is ineffective as second-line
      chemotherapy for metastatic uveal melanoma.

PMID- 15577313
TI  - Early onset may predict G101W CDKN2A founder mutation carrier status in Ligurian
      melanoma patients.
AB  - Although the presence of multiple cases of melanoma on the same side of a family
      is the best predictor of germline CDKN2A mutation, other features (i.e. early age
      at onset) may be useful to identify carriers. We analysed the records of 682
      hospital-based Ligurian melanoma patients. Of these, 238 cases (34 familial, 14
      non-familial multiple primary and 190 non-familial single primary melanomas) were
      consecutively enrolled for screening of the CDKN2A and CDK4 genes. Screening of
      the 34 familial patients revealed that nine were carriers of the CDKN2A G101W
      founder mutation. Of the 14 non-familial multiple primary melanoma patients,
      three carried the G101W founder mutation and one the P48T mutation. For the non
      familial patients with a single melanoma, 17 of 190 carried germline CDKN2A
      mutations, with most (16/17) carrying the G101W Ligurian founder mutation and one
      a novel single base pair substitution, D74Y. The effect of mutation on age at
      diagnosis was significant (P=0.012) after correcting for melanoma type (familial
      or non-familial), number of primaries (single or multiple), gender and disease
      occurrence (incident or prevalent). Early age at onset may be a good predictor of
      CDKN2A mutation in Liguria, where the G101W founder mutation is prevalent among
      melanoma patients, independent of family history.

PMID- 15577314
TI  - BRAF mutations are detectable in conjunctival but not uveal melanomas.
AB  - Activating mutations in exon 15 of BRAF have been detected in a high proportion
      of cutaneous melanomas. To determine whether such mutations are a feature of
      conjunctival or uveal melanomas, we screened DNA from these tumours. Twenty-one
      conjunctival and 88 uveal tumours were included in the study. Mutation analysis
      of BRAF exons 11 and 15 was undertaken using a combination of conformationally
      sensitive gel electrophoresis and direct sequencing. Mutations in exon 15 were
      detected in three of the conjunctival tumours (two V599E and one E585 K). None of
      the uveal tumours possessed a BRAF mutation in either exon 15 or 11. We conclude
      that uveal melanomas arise independently of oncogenic BRAF mutations, but the
      development of a proportion of conjunctival tumours involves mutation of this
      gene.

PMID- 15577315
TI  - Class II transactivator (CIITA) isoform expression and activity in melanoma.
AB  - In contrast with melanocytes, melanomas display constitutive expression of HLA-DR
      (HLA-DR+). This abnormal expression has been associated with tumour progression
      and metastatic dissemination. We have previously reported that this deregulation
      of HLA-D genes is due to the abnormal constitutive expression of the lymphocyte
      specific isoform of class II transactivator (B-CIITA), in addition to its
      fibroblast form (F-CIITA), which is usually expressed in major histocompatibility
      complex (MHC) class II-negative interferon-gamma-induced cell types, such as
      melanocytes. In this study, we investigated the abnormal expression of B-CIITA in
      a panel of melanoma cell lines displaying differential HLA-DR expression
      profiles, and analysed whether such a molecular event can participate in tumour
      progression. Our results showed that the abnormal expression of B-CIITA did not
      have any particular effect, in comparison with F-CIITA, on the classical activity
      of CIITA HLA-D gene regulation. As CIITA has also been shown to regulate genes
      other than HLA-D, we evaluated the modulation of those encoding cyclin D1, YARS
      (tyrosyl-tRNA synthetase) and TRIP1 (transforming growth factor (TGF)-beta
      receptor-interacting protein), proteins involved in cell cycle/apoptosis balance,
      angiogenesis and resistance to TGF-beta, respectively. In contrast with other
      cell types, neither B-CIITA nor F-CIITA was able to modulate these genes in
      melanoma cell lines. Thus, the activity of CIITA, whether lymphocyte-specific or
      fibroblast-specific, is restricted to HLA-D gene expression in these tumours.
      Accordingly, our data suggest that CIITA is not involved per se in tumour
      progression; rather, it is the MHC class II molecules themselves, through tumour
      antigen presentation and the induction of tumour antigen-specific CD4 lymphocyte
      anergy, that may participate in immune escape and melanoma progression.

PMID- 15577316
TI  - Differential expression of melanoma-associated antigens and molecules involved in
      antigen processing and presentation in three cell lines established from a single
      patient.
AB  - Tumour cells are able to evade the immune system by using several 'escape
      mechanisms'. Downregulation of molecules involved in the processing and
      presentation of self-antigens has been reported. However, these adaptations have
      not been compared in metastases in different anatomical locations but derived
      from a single patient. We investigated three melanoma cell lines--MJT1 from the
      parietal lobe of the brain, MJT3 from the cerebellum and MJT5 from the left side
      of the neck--established from biopsies excised from a 45 year old female patient.
      Although human leukocyte antigen (HLA) class I was detected in all three cell
      lines by flow cytometry using an anti-HLA monomorphic antibody, further
      serological analysis demonstrated HLA B38 loss in all three cell lines, HLA B7
      downregulation in MJT5 (skin metastases) and B7 loss in MJT3 and MJT1 (brain
      metastases) compared with the HLA type of the patient's normal autologous
      lymphocytes. Interferon-gamma (IFNgamma) treatment increased the expression of
      HLA class I and transporters associated with antigen processing 1 (TAP1) in all
      three cell lines. De novo HLA class II molecule expression was observed after
      IFNgamma treatment in MJT3 and MJT5. Western blot and reverse transcription
      polymerase chain reaction results revealed heterogeneity of melanoma-associated
      antigen (MAA) expression in the cell lines: MJT3 cells expressed higher levels of
      MAAs than the other two cell lines. In conclusion, this study has demonstrated
      that three metastatic lesions from a single patient can have differential
      expression of molecules involved in antigen processing (TAP1) and presentation
      (HLA I and II), but that expression of these molecules is modulated by IFNgamma
      to a similar degree in all cell lines. In contrast, the downregulation of
      expression of specific MAAs between the three cell lines was unaffected by the
      addition of IFNgamma.

PMID- 15577317
TI  - Chromosomal abnormalities, p53 and Bcl-2 expression and clinical outcome in
      choroidal melanoma.
AB  - OBJECTIVE: To determine whether alterations of p53, Bcl-2 and chromosomes were
      present in choroidal melanoma and to further characterize the prognosis of these
      changes. METHODS: The expression of p53 and Bcl-2 protein was assessed by
      immunohistochemistry from paraffin blocks. Tumours were analysed by comparative
      genomic hybridization (CGH) to identify chromosomal aberrations. Fifteen tumours
      were studied, and the survival results were compared by Spearman correlation
      analysis with a mean follow-up of 36.5+/-8 months. The majority of tumours were
      mixed (eight cases), and the others were spindle cell (four cases) and
      epithelioid cell (three cases) types. Four patients have already died due to
      metastatic disease. RESULTS: p53 was expressed at a low percentage in only two
      tumours. There were no differences in Bcl-2 expression in our cases. Bcl-2 was
      expressed by the majority of cells in all cases. Chromosomal copy number
      aberrations were detected in 10 of the 15 patients by CGH analyses. A gain at
      chromosome 8 and a loss at chromosome 3 were the most frequently seen
      abnormalities. The other aberrations observed were losses at 6q, 7q14 and 17p13
      15, and gains at 6p and 18q. Two of the three cases with a loss at 17p13 showed a
      low percentage expression of p53. No relationship was determined between the
      chromosomal abnormalities, cell type, expression of p53 and survey. The presence
      of a chromosome 6q deletion in two of the four patients who died of metastatic
      disease may indicate that chromosome 6q deletion may be correlated with a poor
      prognosis. CONCLUSIONS: Our results suggest that choroidal melanomas show high
      levels of chromosomal alterations. Further studies are necessary to determine the
      correlation between chromosomal abnormalities and prognosis.

PMID- 15577318
TI  - N-glycoproteins bearing beta1-6 branched oligosaccharides from the A375 human
      melanoma cell line analysed by tandem mass spectrometry.
AB  - Tumour-associated alterations of cell surface glycosylation play a crucial role
      in the adhesion and metastasis of cancer cells. It is well known that the
      metastatic potential is associated with increased GlcNAc beta1-6 branching in N
      glycans of tumour cells specifically recognized by a lectin from Phaseolus
      vulgaris leukoagglutinin (PHA-L). We identified proteins bearing GlcNAc beta1-6
      branched N-glycans in the A375 human melanoma cell line by affinity
      chromatography separation on a PHA-L agarose column, followed by
      immunoidentification and tandem mass spectrometry (MS/MS) analysis. Amongst the
      proteins identified were integrin subunits alpha2, alpha3, alpha5 and beta1, as
      well as N-cadherin and lysosome-associated membrane proteins (LAMP-1 and LAMP-2).
      In addition, L1, Mac-2 binding protein (Mac-2-BP), activated leukocyte cell
      adhesion molecule/CD166 (ALCAM) and melanotransferrin were shown to react with
      PHA-L. Some of these proteins are connected mainly with nervous tissues or the
      immune system and play a crucial role in cell adhesion processes. The presence of
      GlcNAc beta1-6 branched oligosaccharides in these proteins may influence their
      adhesion properties, reducing adhesion of the cells to the extracellular matrix
      (ECM) and thus facilitating tumour cell invasion.

PMID- 15577319
TI  - Cutaneous melanoma in childhood and adolescence: retrospective study of 32
      patients.
AB  - This study was performed to analyse the behaviour, risk factors, prognosis and
      evolution of cutaneous melanoma in childhood and adolescence treated in a single
      institution. A retrospective study was performed between 1980 and 2000 of
      patients aged 18 years or younger followed at the Hospital do Cancer de Sao
      Paulo, Brazil. Data included demographic status, risk factors, clinical and
      histopathological characteristics of the primary and metastatic lesions, stage
      and follow-up. Seventeen female (53.1%) and 15 male (46.9%) patients were
      studied. Twelve patients (37.5%) were aged 12 years or younger. The trunk was the
      most common location (14 patients; 43.8%). Five patients (15.6%) had giant
      congenital melanocytic naevus, three (9.4%) had xeroderma pigmentosum and one
      (3%) had dysplastic melanocytic naevus. Nodular melanoma was the most frequent
      histological type and 43.8% had a thickness of more than 4 mm. Five of the 32
      patients (15.6%) were lost to follow-up and 15 (46.9%) were alive at the last
      year's follow-up, 11 (34.4%) without disease and four (12.5%) with active
      disease. The 5-year overall survival was 64.34%. An overall survival of 11.71%
      was found in patients with visceral metastasis with or without cutaneous and/or
      lymph node involvement, whereas the corresponding value was 90.48% (P
      value=0.0002) in patients with only cutaneous and/or lymph node metastasis.
      Cutaneous melanomas are uncommon in the young and are seldom diagnosed in the
      early stages, perhaps due to a reluctance to accept this diagnosis in this age
      group. Prevention and early stage diagnosis depend upon the recognition that this
      disease is present in the young.

PMID- 15577320
TI  - The prognostic role of CD4+ and CD8+ lymphocytes during chemoimmunotherapy in
      metastatic melanoma.
AB  - We have observed that an early increase in the CD4+/CD8+ ratio of metastatic
      melanoma patients during chemoimmunotherapy is the most favourable independent
      prognostic factor. In this study, 87 patients with metastatic melanoma were
      monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) before and
      during chemoimmunotherapy (dacarbazine, vinblastine, lomustine and bleomycin or
      dacarbazine alone plus interferon-alpha) to confirm our previous observation.
      Blood samples were systematically obtained from patients who received either of
      these chemoimmunotherapies. The frequencies of peripheral blood lymphocyte
      subsets were monitored by flow cytometry using monoclonal antibodies OKT4 (CD4+,
      T-helper cells) and OKT8 (CD8+, T-suppressor cells). The overall response rate
      was 46.5%, and the median overall survival was 9.3 months. Patients with pre
      treatment CD4+ levels above the mean level, who later responded to therapy, had a
      median survival of 28.1 months vs. 10.2 months for responders with low pre
      treatment CD4+ levels (P=0.053, log-rank test). Responders with decreasing CD8+
      levels had a median survival of 27.8 months vs. 10.8 months for responders with
      increasing CD8+ levels (P=0.04, log-rank test). Similarly, responding patients
      with an increasing CD4+/CD8+ ratio had a median survival of 28.1 months vs. 10.5
      months for those with decreasing ratios (P=0.002, log-rank test). Non-responders
      showed no difference in median survival irrespective of low or high pre-treatment
      CD4+ lymphocytes, increasing or decreasing CD8+ levels, or increasing or
      decreasing CD4+/CD8+ ratios. This follow-up study confirms that the monitoring of
      CD4+ and CD8+ lymphocytes may provide important predictive and prognostic
      information in metastatic melanoma patients receiving chemoimmunotherapy.

PMID- 15577321
TI  - Mitochondrial DNA instability in malignant melanoma of the skin is mostly
      restricted to nodular and metastatic stages.
AB  - Ultraviolet (UV) radiation is thought to be a major contributor to the
      development of sporadic malignant melanoma of the skin. It may induce alterations
      in genomic or mitochondrial DNA (mtDNA), especially C to T or CC to TT changes.
      Mutations or other alterations in mtDNA have been reported in a variety of human
      cancers and may be due to different mechanisms. In this study, we have attempted
      to elucidate whether aberrations in the mtDNA of melanoma are due to UV radiation
      or other factors by investigating two parts of the mitochondrial D-loop and two
      mitochondrial genes, as well as looking for the delta4977 mtDNA deletion and
      mtDNA duplications, in 61 primary malignant melanomas and neighbouring normal
      skin tissue (in 70% of primary tumours; otherwise, corresponding blood samples).
      Point mutations were a rare feature, occurring in only seven tumour samples and
      never as a C to T change, whereas mtDNA instability in the D-loop (mtMSI) was
      found in 13% of primary nodular tumours and 20% of metastases. A de novo
      delta4977 mtDNA deletion was demonstrated in 10% of melanomas; in 20% of
      patients, mtDNA duplications and/or the delta4977 mtDNA deletion was detectable.
      Our data indicate that mtDNA alterations in malignant melanoma are not induced by
      UV radiation. In addition, point mutations and mtMSI were mostly a feature of
      nodular and metastatic melanoma samples.

PMID- 15577322
TI  - Human melastatin 1 (TRPM1) is regulated by MITF and produces multiple polypeptide
      isoforms in melanocytes and melanoma.
AB  - Melastatin 1 (MLSN1), originally identified as melanoma metastasis suppressor,
      represents a TRPM subfamily of transient receptor potential (TRP) proteins which
      serve diverse biological roles in a wide variety of cell types. Down-regulation
      of MLSN1 expression in human cutaneous melanoma, as indicated by in situ
      hybridization, appears to be a prognostic marker for melanoma metastasis.
      However, the exact physiological function(s) of MLSN1, the mechanism(s) involved
      in the regulation of its expression and its role in melanoma tumour progression
      are not yet clear. In this study, we identified a 654 bp upstream sequence of
      MLSN1, containing four E boxes (E1-E4), including an 11 bp M box (E4), that is
      sufficient for melanocyte-specific transcription and activation by the melanocyte
      transcription factor MITF (a bHLH-zip factor). Deletion analysis showed that the
      two distal E boxes (E3 and E4) in the MLSN1 promoter are required for both its
      activation by MITF and its constitutive activity in melanoma cells. Western blot
      analysis using polyclonal rabbit anti-human MLSN1 antibodies identified several
      polypeptides, presumably generated by both alternative splicing of MLSN1
      messenger RNA (mRNA) and proteolytic cleavage, in both melanocytes and metastatic
      melanoma cells. Thus, multiple mechanisms appear to regulate MLSN1 expression in
      melanocytes and melanoma cells.

PMID- 15577323
TI  - Biochemotherapy in patients with advanced vulvovaginal mucosal melanoma.
AB  - Patients with advanced vulvovaginal mucosal melanoma generally have a dismal
      prognosis, and no effective systemic therapy for the disease has been reported.
      The objective of this retrospective clinical study was to assess the clinical
      benefit of biochemotherapy in this patient population. We evaluated the medical
      records of all patients with advanced vulvovaginal mucosal melanoma treated with
      biochemotherapy at our institution. Our search yielded 11 patients with adequate
      documentation for study inclusion: eight patients had undergone treatment with
      cisplatin (CDDP), vinblastine (VB), dacarbazine (DTIC), interferon-alpha (IFN)
      and interleukin-2 (IL-2), one with CDDP, VB, DTIC and IFN, one with CDDP,
      temozolomide and IFN, and one with CDDP, VB, DTIC, tamoxifen, IFN and IL-2. All
      IL-2 treatments were administered intravenously. The median follow-up duration
      was 10 months (range, 2-44 months). Four patients (36%) showed partial responses,
      but none showed a complete response. Two patients did not return for follow-up
      evaluation after the completion of treatment. The median time to disease
      progression in all 11 patients was 3 months; however, the median time to disease
      progression in those with a partial response or stable disease was 6 months. One
      patient was alive at the last documented follow-up visit (51 months). The median
      overall survival duration from the start of biochemotherapy was 10 months.
      Biochemotherapy appears to have significant activity against advanced
      vulvovaginal melanoma, and should be considered as a systemic treatment option
      for advanced, metastatic, vulvovaginal melanoma.

PMID- 15577324
TI  - Sentinel node biopsy for melanoma: a study of 241 patients.
AB  - The aim of this study was to evaluate the sentinel node biopsy (SNB) technique
      for melanoma using both radiocolloid and blue dye in 241 clinically N0 patients
      with melanomas >1.0 mm, or thinner lesions exhibiting regression/ulceration. We
      showed that an increase in injected radioactivity increased both the number of
      visualized nodes at lymphoscintigraphy and the number of SNs removed surgically.
      At least one SN was removed in 98% (236) of patients, and all nodes were
      identified with the probe. Seventy-four per cent of the 194 patients injected
      with blue dye had stained SNs. In 46% (144) of the lymph node basins, there was a
      discrepancy between the nodes visualized at lymphoscintigraphy and the nodes
      removed at surgery. There were 38 unusually located nodes. Only eight of these
      were removed surgically; none contained metastases. SN metastases were detected
      in 22% (53) of patients. There were nine haematoxylin and eosin (HE)-negatives,
      all of which were found by immunohistochemistry. The false negative rate for the
      SNB procedure was 4% (2/55). The complication rate was 6% after SNB and 29% after
      complete node dissection. In conclusion, SN status is a strong prognostic factor
      in melanoma patients, and SNB has made the approach to radical lymphadenectomy
      more rational.

PMID- 15577325
TI  - Phase II study of thalidomide in patients with metastatic malignant melanoma.
AB  - Thalidomide has anti-angiogenic and immunomodulatory activity, exhibiting
      antitumour effects in patients with multiple myeloma and, more rarely, in several
      other solid tumours. We evaluated the single-agent antitumour activity and
      toxicity profile of thalidomide in patients with metastatic malignant melanoma,
      as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF)
      levels]. A two-stage Gehan method was used with a stopping rule after 14
      consecutive non-responding patients. Thalidomide was given orally at a daily dose
      of 200 mg/day, which was then escalated every 2 weeks by 200 mg/day as tolerated
      to a maximum of 800 mg/day. Patients were evaluated every 8 weeks for response
      using the World Health Organization (WHO)-27 criteria. Fourteen patients were
      enrolled and no objective responses were observed, with one stable disease and
      one mixed response. The dose-limiting toxicities were constipation, dizziness and
      somnolence. Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor
      and fatigue. The plasma pharmacokinetics of thalidomide were comparable with
      those of previous studies in normal volunteers and in patients with advanced
      prostate cancer. Serum levels of b-FGF and VEGF did not change significantly
      following drug administration. In conclusion, thalidomide showed poor activity,
      but acceptable toxicity, in patients with metastatic melanoma. Future studies
      should explore this agent in combination with other biological agents or
      cytotoxic agents, such as temozolomide.

PMID- 15577326
TI  - The role of preoperative ultrasonography in reducing the number of sentinel lymph
      node procedures in melanoma.
AB  - Sentinel lymph node (SLN) biopsy is the most effective method to nodally stage
      patients with melanoma. However, SLN metastases are an indication for a complete
      regional lymphadenectomy. The aim of this study was to evaluate the ability of
      ultrasound (US) and US-guided fine needle aspiration biopsy (US-FNAB) to reduce
      the number of patients requiring a second surgical procedure. Fifty-seven
      patients with melanoma underwent preoperative US of the regional lymph nodes
      before SLN biopsy. In patients with US malignant lymph nodes, US-FNAB was
      performed. Only patients with cytologically proven lymph node metastases
      proceeded directly to a complete regional lymphadenectomy, whereas, in all
      others, SLN biopsy was performed. Fourteen patients (25%) had metastases in the
      regional lymph nodes. There were 40 benign and 17 malignant US results. US-FNAB
      was performed in 14 patients. It was positive in three, negative in nine and
      inadequate sampling was obtained in two. The sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of US were 71%, 84%,
      59% and 90%, respectively. US of the regional lymph nodes with US-FNAB enables
      the safe selection of patients who should proceed directly to a complete regional
      lymphadenectomy. However, the sensitivity and PPV of the method are low.

PMID- 15577327
TI  - Malignant melanoma in Taiwan: a prognostic study of 181 cases.
AB  - This study was performed to determine the characteristics and clinical outcome of
      patients with cutaneous malignant melanoma in Taiwan. The medical records of
      patients with primary cutaneous melanoma between 1992 and 2001 at Chang Gung
      Memorial Hospital (CGMH) were retrieved from the cancer registry. Survival was
      analysed by the Kaplan-Meier method. Univariate and multivariate analyses of
      factors associated with survival were performed using the Cox proportional hazard
      model. One hundred and eighty-one cases were retrieved from the cancer registry
      of CGMH. The male to female ratio was 1 : 1.13. The most common age of onset was
      the sixth decade. The median age of onset was 61 years (2-95 years). There were
      105 cases (58%) of acral lentiginous melanoma (ALM), 55 cases (30.4%) of nodular
      melanoma (NM), 19 cases (10.5%) of superficial spreading melanoma (SSM) and two
      cases (1.1%) of lentigo maligna melanoma. The median survival of the 181 patients
      was 3.71 years, and the 5-year survival rate was 45.63%. Five-year survival rates
      of patients with stages I, II, III and IV disease were 84.39%, 56.03%, 34.7% and
      0%, respectively. Sex, Breslow thickness, Clark's level, pathological type and
      age were significant prognostic factors. There were no survival differences
      between ALM and NM. Both ALM and NM were associated with a poor prognosis when
      compared with SSM. In conclusion, ALM is the most common type of cutaneous
      malignant melanoma in Taiwan. The prognostic factors in Taiwan are similar to
      those in melanoma-prevalent countries.

PMID- 15577328
TI  - Serum bcl-2 and survivin levels in melanoma.
AB  - This study was conducted to investigate the serum levels of bcl-2 and survivin in
      patients with melanoma and the relationship with tumour progression and known
      prognostic parameters. Forty-four patients with cutaneous melanoma were
      investigated. Serum samples were obtained on first admission before adjuvant and
      metastatic treatment were given and at follow-up. Serum bcl-2 and survivin levels
      were determined using enzyme immunometric assay (EIA) and enzyme-linked
      immunosorbent assay (ELISA). The baseline serum bcl-2 levels were significantly
      higher in patients with melanoma than in the control group (P=0.01). For the
      serum survivin levels, no difference was found (P=0.6). No significant
      correlations were found between the prognostic parameters analysed and the serum
      survivin concentrations. The same was true of the serum bcl-2 values, except for
      the age of the patient (P=0.025) and nodal involvement (P=0.003). No significant
      relationship was found between the serum levels of bcl-2 and survivin (r=-0.13,
      P=0.4). In node-positive patients (n=8) both of these anti-apoptotic substances
      were unchanged after interferon-alpha-2b therapy. However, serum survivin
      concentrations were significantly increased in 10 patients with metastatic
      melanoma who underwent dacarbazine (DTIC)-based cytotoxic chemotherapy (P=0.047).
      A similar finding was not determined for the serum bcl-2 levels. In conclusion,
      the results of this study suggest that decreased apoptosis is associated partly
      with an increase in serum bcl-2. However, much research continues in this field,
      and exciting new knowledge will ultimately emerge.

PMID- 15577329
TI  - Mofarotene-induced inhibition of melanoma cell motility by increasing vinculin
      containing focal contacts.
AB  - Tumour cell motility, which is dependent on the organization of the cytoskeleton,
      is considered to play an important role in the spread of malignant melanoma.
      Therefore, retinoids, which are modulators of cytoskeletal organization, may
      affect the motile activity of melanoma cells. In this study, the effects of the
      arotinoid mofarotene on single cell motility and vinculin organization of the
      highly metastatic melanoma cell line K-1735-M2 were determined. Melanoma cells
      were cultivated in a temperature- and CO2-controlled microincubator, which was
      located on the microscope stage. Cell movements were evaluated quantitatively
      from time-lapse video recordings using an IBAS image analysis system. Vinculin
      distribution was evaluated using confocal laser scanning microscopy and a
      specially developed computerized image analysing program. In addition, melanoma
      cell invasion was tested on the embryonic chick heart model. Although 10 microM
      mofarotene did not reduce the translocative movements of melanoma cells, it
      significantly inhibited stationary motility, including fast plasma membrane
      movements and changes in shape. Mofarotene also showed a pronounced effect on the
      organization of vinculin-containing cell-substratum adhesion plaques. In retinoid
      treated cells, the numbers of vinculin plaques per cell, and particularly those
      in the marginal areas of the cells, were significantly increased compared with
      untreated controls. Furthermore, the compound reduced the invasiveness of
      melanoma cells in a three-dimensional tissue culture model. In conclusion, our
      data demonstrate that mofarotene, an already almost forgotten synthetic retinoid,
      shows interesting effects on melanoma cells, which may be relevant for a slowdown
      of tumour spread.

PMID- 15577330
TI  - Inhibition of melanoma growth after treatment with dendritic cells in a Tyr-SV40E
      murine model requires CD4+ T cells but not CD8+ T cells.
AB  - Melanomas are promising targets for immunotherapy, as they express a number of
      tissue-specific antigens against which immune responses can be elicited. We have
      previously described transgenic mice in which malignant cutaneous melanomas are
      produced. The 1042 melanoma cell line, derived from a primary melanoma in one of
      these mice, was used here to generate tumours by subcutaneous inoculation in
      syngeneic animals. All mice injected with 1 x 10(6) cells of the 1042 cell line
      developed a tumour. CD4+ T cells, CD8+ T cells and macrophages infiltrated the
      tumours. Treatment with dendritic cells pulsed with peptides from melanogenic
      proteins slowed tumour growth and resulted in increased numbers of infiltrating
      lymphocytes and macrophages, expansion of CD4+ T cells specific for 1042 cell
      antigens, and increased levels of 1042-specific immunoglobulin G1 (IgG1) and IgM
      in serum. The frequency of cytotoxic T lymphocytes (CTLs) specific for the MART-1
      melanocytic antigen did not increase after dendritic cell treatment. Indeed, the
      presence of CD8+ T cells was apparently not required for the anti-tumour effects:
      slowing of tumour growth was not abrogated in animals depleted of CD8+ T cells
      using antibodies, or in syngeneic CD8-/- animals. In contrast, treatment with
      dendritic cells + peptides was ineffective after depletion of CD4+ T cells and in
      syngeneic CD4-/- mice. This experimental system therefore provides an opportunity
      to investigate CD4-dependent anti-tumour effector mechanisms, and for studies
      designed to activate the quiescent CTLs which infiltrate melanomas.

PMID- 15577331
TI  - Anorectal melanoma: issues of influence for therapeutic decisions.

PMID- 15577333
TI  - Do we detect a new spectrum of biologically 'benign' melanomas in the dermoscopy
      era?

PMID- 15577334
TI  - Reconstruction of a skin and bone defect of the parietal region using a
      superficial cervical artery skin flap.

PMID- 15577335
TI  - Upper eyelid reconstruction.
AB  - There are several options available for upper eyelid reconstruction that depend
      on the extent of involvement of the anterior and posterior lamella. Knowledge of
      the anatomy will ensure that in addition to the creation of an aesthetically
      acceptable eyelid reconstruction, a functional upper lid will be restored. The
      purpose of this article is to outline the anatomy of the eyelid, to analyze the
      components of eyelid defects, and to provide options for lid reconstruction.

PMID- 15577336
TI  - Coronal ring involvement in patients treated for unilateral coronal
      craniosynostosis.
AB  - The etiopathology of the clinical entity normally referred to as unilateral
      coronal synostosis is commonly used to connote unilateral fusion of the
      frontoparietal suture. However, other sutures in the coronal ring may exhibit
      synostosis concomitant with or independent from frontoparietal synostosis and
      give rise to similar clinical phenotypes. This study retrospectively analyzes
      high-resolution computed tomographic data sets to determine patency of sutures
      within the coronal ring. Computed tomographic scan digital data from 33 infants
      who subsequently underwent surgical correction of unilateral coronal synostosis
      were assessed for sutural patency using Analyze imaging software. The
      frontosphenoidal suture was subdivided into intraorbital frontosphenoidal and
      extraorbital frontosphenoidal portions, and the patency of the frontoethmoidal
      suture was also assessed. Patients were sorted into two groups on the basis of
      the status of their frontosphenoidal sutures: group 1 had patent frontosphenoidal
      but synostotic frontoparietal sutures (n = 21) and group 2 had both
      frontosphenoidal and frontoparietal synostoses. Observer reproducibility was
      tested. The vertical and horizontal dimensions of the bony orbit and the
      endocranial base deflection angle were measured with the observer blinded with
      regard to sutural status group. Frontoethmoidal synostosis was not noted in any
      patients in either group. Two patients had no frontoparietal suture synostosis
      with isolated intraorbital frontosphenoidal and extraorbital frontosphenoidal
      suture closures. Suture diagnosis reproducibility was 99 percent. In group 1, the
      ipsilateral-to-contralateral vertical orbit dimension ratio averaged 1.11,
      whereas in group 2 it averaged 1.04 (p < 0.05). The ratio of horizontal orbit
      measurements was not significantly different between groups. In both groups, the
      endocranial base was deflected ipsilateral to the synostotic frontoparietal
      suture, with an average angle of 12 degrees in group 1 and 17 degrees in group 2
      (p < 0.005). The extent of synostosis along the coronal sutural ring contributes
      to the dysmorphology of the orbit and the endocranial base deflection in patients
      whose clinical phenotypic diagnosis is unilateral coronal synostosis.

PMID- 15577337
TI  - Comparison of the radial forearm flap and the thinned anterolateral thigh
      cutaneous flap for reconstruction of tongue defects: an evaluation of donor-site
      morbidity.
AB  - The radial forearm flap is commonly used for reconstruction of tongue defects
      following tumor extirpation. This flap is easy to harvest and offers thin tissue
      with large-caliber vessels. However, its use leaves behind a conspicuous
      aesthetic deformity in the forearm and requires the sacrifice of a major artery
      of that limb, the radial artery. The anterolateral thigh cutaneous flap has found
      clinical applications in the reconstruction of soft-tissue defects requiring thin
      tissue. More recently, in a thinned form, the anterolateral thigh flap has been
      used for reconstructing defects of the tongue with functional results equivalent
      to that of the radial forearm flap. For the reconstruction of tongue defects,
      these two flaps could provide similar soft-tissue coverage, but they seem to
      result in different donor-site appearances. The donor site is closed primarily,
      leaving only a linear scar that is inconspicuous with normal clothing, and no
      functional deficit is left behind in the thigh. Thus, for the supply of flaps for
      tongue defects, a comparison between the radial forearm flap and the
      anterolateral thigh flap donor sites is provided in this study. Between December
      of 2000 and August of 2002, 41 patients who underwent reconstruction of defects
      of the tongue using either a radial forearm flap or an anterolateral thigh flap
      were evaluated. The focus was on the evaluation of the functional and aesthetic
      outcome of the donor site after harvesting these flaps for the purpose of
      reconstructing either total or partial tongue defects. Finally, a comparison was
      performed between the donor sites of the two flaps. The disadvantages of the
      radial forearm flap include the conspicuous unattractive scar in the forearm
      region, pain, numbness, and the sacrifice of a major artery of the limb. In some
      patients, the donor-site scar of the forearm acted as a social stigma, preventing
      these patients from leading a normal life. In contrast, the anterolateral thigh
      cutaneous flap, after thinning, achieved the same results in reconstructing
      defects of the tongue without the associated donor-site morbidity. Most
      importantly, the donor site in the thigh could be closed primarily in almost all
      patients without any functional deficit. The thinned anterolateral thigh
      cutaneous flap is a viable substitute for the radial forearm flap when
      reconstructing defects of the tongue. The results achieved are similar to those
      of the radial forearm flap, and the donor-site morbidity is significantly
      decreased.

PMID- 15577338
TI  - Treatment of mandibular angle fractures with a matrix miniplate: a preliminary
      report.
AB  - Mandibular angle fractures are technically challenging, and a spectrum of
      techniques for treatment of these fractures has been proposed in the literature.
      Currently, fixation with one or two miniplates has become a widely accepted
      method of providing internal fixation and eliminating the need for postoperative
      maxillomandibular fixation. In this study, the utility of a single 2.0-mm matrix
      miniplate for mandibular angle fracture management was examined. In a laboratory
      biomechanical analysis, the overall stability of the single 2.0-mm matrix
      miniplate compared favorably with two 2.0-mm miniplates in a simulated fracture
      setting. The matrix miniplate demonstrated an overall better intrinsic stability,
      more resistance to out-of-plane fracture movement, and a higher load tolerance
      when motion out-of-plane was challenged. Clinically, the matrix miniplate
      performed well. In a series of 22 consecutive patients, there were no cases of
      nonunion, malunion, or plate failure. Two patients developed infection that was
      managed in both cases by drainage with maintenance of the miniplate. Both went on
      to full union. These results compare very favorably to previously published
      series using one or two miniplates.

PMID- 15577340
TI  - Anatomic study of the vasculature of the submental artery flap.
AB  - The submental artery island flap is a versatile option in head and neck
      reconstruction. This flap may be used for the coverage of perioral, intraoral,
      and other facial defects, leaving a relatively acceptable donor-site scar. In
      this study, the submental region of 13 formalin-fixed cadavers was dissected
      bilaterally. Comprehensive anatomical information regarding the pedicle of the
      flap and its relationship with the important adjacent structures is provided. The
      mean values of the measurements of the facial and submental arteries were as
      follows: the facial artery was 2.7 mm in diameter at the origin, and it crossed
      the mandibular border 26.6 mm from the mandibular angle. The origin of the
      submental artery was 27.5 mm from the origin of the facial artery, 5.0 mm from
      the mandibular border, and 23.8 mm from the mandibular angle. The diameter of the
      submental artery was 1.7 mm at the origin. The artery was found mostly to course
      superficial to the submandibular gland. In one case, the artery passed through
      the gland. The total length of the submental artery was 58.9 mm. The artery
      anastomosed with the contralateral artery in 92 percent of the cadavers. The
      submental artery was deep to the anterior belly of the digastric muscle in 81
      percent of the cases. This study presents detailed anatomical data about the
      location, dimension, and relationship of the facial artery, the submental artery,
      and the submental vein that may be useful during dissection of the submental
      artery island flap.

PMID- 15577341
TI  - Current preferences for breast reduction techniques: a survey of board-certified
      plastic surgeons 2002.
AB  - The purpose of this survey was to assess the current trends in breast reduction
      techniques and to compare satisfaction rates and complications associated with
      traditional incision and limited incision techniques. In September of 2002, a
      breast reduction survey was sent to 1500 members of the American Society for
      Aesthetic Plastic Surgery; 554 of the members returned the survey. Questions
      elicited categorical answers, and the data were evaluated using the chi-square
      test and the comparison of two proportions. The results showed that 56 percent of
      the respondents use only the inferior pedicle and Wise pattern techniques,
      whereas 6.9 percent of the respondents use only the limited incision techniques.
      Physician satisfaction was rated as 4 on a scale of 1 (unsatisfied) to 5 (very
      satisfied) for both the limited incision and traditional incision groups. Patient
      satisfaction was rated as 4 for the limited incision group and as 5 for the
      traditional incision group. This difference in patient satisfaction per surgeon
      was statistically significant (p < 0.05). The traditional group reported a lower
      complication rate than did the limited incision group (p < 0.05). The most
      frequent complications for the traditional incision group were compared with
      those of the limited incision group. Practice profiles, liposuction, and opinions
      regarding future changes in breast surgery were also analyzed. The majority of
      surgeons reported that they did not anticipate changing their practices to
      accommodate advances in limited incision techniques; however, 89 percent reported
      that the new limited incision techniques and liposuction are trends that are here
      to stay.

PMID- 15577343
TI  - Breast cancer in patients with prior augmentation: presentation, stage, and
      lymphatic mapping.
AB  - The purpose of this study was to determine whether breast cancer patients who had
      prior breast augmentation presented at a more advanced stage than nonaugmented
      breast cancer patients, and to determine the mode of presentation and
      effectiveness of lymphatic mapping and sentinel lymph node biopsy in this same
      group of patients. A total of 4186 breast cancer patients from 1987 to 2002 were
      reviewed. Patients who had augmentation before their diagnosis of breast cancer
      were compared with a control group of nonaugmented breast cancer patients. The
      Wilcoxon rank sum test was used to compare tumor size, node positivity, and
      stage. The patient's age at presentation was also compared by the two-sided
      pooled t test. Seventy-six patients who previously underwent augmentation were
      identified with 78 breast cancers. Seventy percent (48 of 69) were initially
      detected by palpation, whereas 30 percent (21 of 69) were initially identified
      mammographically. Fifty-three percent (n = 41) underwent mastectomy and 47
      percent (n = 37) underwent a lumpectomy. This compares with a 63.6 percent (2615
      of 4110) breast conservation rate in the nonaugmented population during the same
      time period. The two groups did not differ regarding (tumor) size (p = 0.77),
      nodal positivity (p = 0.32), or stage (p = 0.34). The mean time between implant
      placement and a diagnosis of breast cancer was 14 years. The average age of the
      patients who had previously undergone augmentation at breast cancer diagnosis was
      49.5 years (SD, 9.0 years) versus 57.1 years (SD, 13.5 years) for the
      nonaugmented patients (p < 0.0001). Forty-nine of the patients underwent
      lymphatic mapping, with a 100 percent success rate in identifying the sentinel
      lymph node. There have been no clinically detected axillary recurrences in the
      patients who had a negative sentinel lymph node biopsy. Breast cancer patients
      who have undergone previous augmentation are more likely to present with a
      palpable mass. This initial mode of detection does not appear to translate into a
      larger tumor size or worse prognosis. Breast conservation and lymphatic mapping
      can be performed successfully in previously augmented patients.

PMID- 15577344
TI  - Reconstruction after conservative treatment for breast cancer: cosmetic sequelae
      classification revisited.
AB  - Patients with suboptimal results following breast conservative therapy are
      presenting more frequently to plastic surgeons as a difficult management problem.
      A three-type "cosmetic sequelae classification" is proposed to evaluate and
      manage these patients. From February of 1991 to November of 2001, 85 patients
      were treated for cosmetic sequelae of breast conservative therapy at the Institut
      Curie. The patients were followed up prospectively for 6 to 132 months (median,
      33 months). They were assessed with regard to age, site and stage of tumor, type
      of initial breast conservative therapy undertaken, corrective operative
      procedures performed, complications, and cosmetic results. Forty-eight patients
      (56.5 percent) had type 1 cosmetic sequelae, 33 patients (38.8 percent) had type
      2, and four patients (4.7 percent) had type 3. Type 1 was managed by
      contralateral symmetrizing procedures. Type 2 was the most difficult to manage by
      means of various procedures. Type 3 required mastectomy and immediate breast
      reconstruction. Type 1 had 97.6 percent good results compared with 82.7 percent
      for type 2. Three of the four type 3 patients had good results. This article
      reaffirms the validity of the cosmetic sequelae classification as a simple,
      practical guide for breast reconstructive surgeons. It discusses the various
      choices of reconstructive procedures available, the importance of preventing
      these cosmetic sequelae, and the role of the plastic surgeon in the planning of
      conservative treatment of breast cancers.

PMID- 15577345
TI  - Ventral rectus fascia closure on top of mesh hernia repair in the sublay
      technique.
AB  - Sublay prosthetic herniorrhaphy has become a widely accepted procedure for
      incisional hernias. To evaluate the effect of fascia closure on top of mesh
      repair on infection, and the recurrence rate, the authors reviewed their data
      regarding herniorrhaphy in the sublay technique. This study was a retrospective
      analysis of 175 consecutive patients who underwent hernia repair by implantation
      of prostheses by means of the Stoppa-Rives technique from December of 1994 to
      December of 2001. All 175 patients had the mesh implanted in the subfascial
      plane, 130 received a light-weight or heavy-weight polypropylene mesh (Vypro or
      Prolene) (74 percent), eight had a polyester mesh (Mersilene) (5 percent), and 37
      had an expanded polytetrafluoroethylene patch (Gore-Tex) (21 percent). After
      sublay mesh positioning, the mesh could not be covered by the fascia in 50 cases;
      in 31 of these cases, a second mesh was placed into the fascial defect. To
      evaluate the influence of the fascia closing procedure on top of the sublay mesh,
      three groups were differentiated: initial fascia closure (n = 125), no fascia
      closure and concomitant mesh interposition (n = 31), and no fascia closure
      without mesh interposition (n = 19). After a mean follow-up of 20 months, 11 deep
      prosthetic infections (8 percent) and 15 hernia recurrences (9 percent) were
      observed. There was an increased risk of mesh infection when the fascia could not
      be closed, but there was no influence of fascia closure on hernia recurrence.
      When the fascia was left open, the placement of a second mesh inlay technique
      reduced mesh infection. The authors' data give evidence that closing the ventral
      fascia after mesh repair in the sublay position is beneficial. When the edges of
      the hernia defect could not be approximated, the suturing of a second mesh into
      the fascia defect was a useful tool for reducing the prosthetic infection rate;
      however, no significant influence on hernia recurrence was observed.

PMID- 15577346
TI  - Direct closure of round skin defects: a four-step technique with multiple
      subcutaneous and cutaneous "figure-of-8" sutures alleviating dog-ears.
AB  - Excisional biopsies of rounded lesions are performed daily by surgeons. The
      objective of this article is to establish a surgical technique for direct closure
      of circular and elliptical defects without the need for additional excision of
      dog-ears. A four-step technique based on multiple cutaneous and subcutaneous
      "figure-of-8" sutures is presented. When correctly placed, these sutures can
      equally distribute the excess tissue along the scar and alleviate dog-ears. The
      results of the 65 presented cases show that this technique yields short scars and
      saves healthy skin. A significant reduction of the length-to-width ratio and the
      arc-to-scar length ratio is obtained. Direct closure of a circular or elliptical
      defect without stipulating a 3:1 length-to-width ratio is feasible. Among the
      advantages of the technique are that no excessive healthy tissue is removed and
      that the scar length is reduced. The long-term outcome is a scar that is thin,
      linear, flat, and concealed in the body structure.

PMID- 15577347
TI  - Distally based anterolateral thigh flap: an anatomic and clinical study.
AB  - The distally based anterolateral thigh flap has been used for coverage of soft
      tissue defects of the knee and upper third of the leg. This flap is based on the
      septocutaneous or musculocutaneous perforators derived from the lateral
      circumflex femoral system. The purpose of this study was to examine the results
      of anatomical variations of the descending branch of the lateral circumflex
      femoral artery and the retrograde blood pressure of the descending branch of the
      lateral circumflex femoral artery so that the surgical technique for raising and
      transferring a distally based anterolateral thigh flap to the knee region could
      be improved. The authors have actually used this flap in three cases. In 11
      thighs of six cadavers, the descending branch of the lateral circumflex femoral
      artery had a rather consistent connection with the lateral superior genicular
      artery or profunda femoral artery in the knee region. The pivot point, located at
      the distal portion of the vastus lateralis muscle, ranges from 3 to 10 cm above
      the knee. In their three cases, the maximal flap size was 7.0 x 16.0 cm and was
      harvested safely, without marginal necrosis. The mean pedicle length was 15.2 +/-
      0.7 cm (range, 14.5 to 16 cm). The average proximal and distal retrograde blood
      pressure of the descending branch of the lateral circumflex femoral artery was
      also studied in another 11 patients, and the anterolateral thigh flap being used
      for reconstruction of head and neck defects showed 58.3 and 77.7 percent of
      proximal antegrade blood pressure, respectively. The advantages of this flap
      include a long pedicle length, a sufficient tissue supply, possible combination
      with fascia lata for tendon reconstruction, and favorable donor-site selection,
      without sacrifice of major vessels or muscles.

PMID- 15577348
TI  - Teleconsultation with the mobile camera-phone in digital soft-tissue injury: a
      feasibility study.
AB  - The purpose of this study was to examine the feasibility of teleconsultation
      using a mobile camera-phone to evaluate the severity of digital soft-tissue
      injury and to triage the injury with regard to management recommendations. With a
      built-in 110,000-pixel digital camera, pictures of the injured digit(s) or
      radiograph were taken by surgical residents in the emergency room and transmitted
      to another camera-phone to be viewed by the remote consultant surgeon. A brief
      medical and trauma history of each patient was relayed also by mobile phone. The
      consultant surgeon then reviewed all of these patients in the emergency room
      shortly after the initial telemedicine referral. Separate triaging for each
      digital injury into three groups was recorded during remote teleconsultation and
      according to actual treatment by the attending surgeon as follows: group I, the
      injury could be managed with conservative treatment, such as secondary intention
      wound healing, or primary closure with or without bone shortening; group II, skin
      grafting or local flap coverage was required for management of the injury; and
      group III, microsurgery such as replantation or free flap coverage was necessary
      to deal with the injury. Later, triaging was also performed individually by three
      junior plastic residents according to image review and patient referral
      information. Teleconsultation through a mobile camera-phone was performed for 45
      patients with injuries of 81 digits from January to May of 2003. Of these 81
      digital injuries, there were 12 cases (15 percent) where disagreement of triaging
      occurred between the teleconsultation and the actual treatment by the attending
      surgeon. In image reviewing, there was 79 percent sensitivity and 71 percent
      specificity in remote diagnosis of the skin defect and 76 percent sensitivity and
      75 percent specificity in remote identification of the bone exposure regarding
      the concordance of opinions of all three surgeons; there was significant
      discordance in triaging in 20 cases (25 percent), and the difference in triaging
      was partly attributed to the inability to show instances of tiny exposed digital
      bone or tendon in some cases under the low-resolution digital image and the
      situation of a bloody oozing wound. In some cases, the difficulty in evaluating
      the probability of primary closure of severely avulsed skin edges or the
      probability of executing replantation for finger amputation also contributed to
      different triaging outcomes. Two neglected diagnoses of transected digital nerves
      were found and influenced triaging, highlighting the importance of on-site
      physical examination during teleconsultation. The telemedicine system using a
      mobile camera-phone based on the global system for mobile communication is
      feasible and valuable for early diagnosis and triaging of digital soft-tissue
      injury in emergency cases, with on-line verbal communication and review of the
      transmitted captured image. This system has the advantages of ease of use, low
      cost, high portability, and mobility. With advances in hardware for digital
      imaging and transmission technology and the development of the third-generation
      advanced mobile phone system in the foreseeable future, this system has potential
      for future applications in telemedicine and telecare.

PMID- 15577349
TI  - Clinical application of fresh fibroblast allografts for the treatment of diabetic
      foot ulcers: a pilot study.
AB  - Diabetic foot ulcers often pose a difficult problem for health care professionals
      because of the defects associated with fibroblast functioning. Although there has
      been much interest recently in the use of topical growth factors for the
      treatment of diabetic foot ulcers, the effects are generally not very dramatic.
      Cryopreserved fibroblast implants, which are able to adjust to a wound's
      environment and provide the desired growth factors and other substances that may
      be lacking in a chronic wound, represent an exciting development and a major
      advance. These products may well provide growth factors in the right
      concentration and in the right sequence, something that has proved difficult to
      achieve with the topical application of recombinant growth factors. However, cell
      activities are impaired by cryopreservation. The purpose of this study was to
      assess the effects of fresh human allogeneic fibroblast grafting for the
      treatment of diabetic foot ulcers. Eight patients with diabetic foot ulcers
      ranging from 6 to 17 weeks in duration were treated. The size of the wounds
      ranged from 2.0 to 6.0 cm2, with three patients exhibiting exposed bones. A
      history of diabetic foot ulcers was present in five patients. Human dermal
      fibroblasts from healthy teenagers were cultured in Dulbecco's modified Eagle
      medium/Ham's F-12 supplemented with 10% autologous serum. The cultured cells were
      applied over the wounds immediately after debridement; fibrin was used as a cell
      carrier. A dressing was then applied with Tegaderm and kept moist until healing
      was complete. The progress and time for complete wound closure and patient
      satisfaction were assessed, with follow-up time ranging from 6 to 18 months.
      Complete wound healing occurred in all patients. Eleven to 21 days were needed
      for complete reepithelization of the wound, and no clinical or laboratory
      abnormalities were noted. Patient satisfaction was also very positive. In this
      study, the use of fresh human fibroblast allografts was found to be a safe and
      effective treatment for diabetic foot ulcers.

PMID- 15577350
TI  - Tolerance induction in composite facial allograft transplantation in the rat
      model.
AB  - Clinical application of composite tissue allograft transplants opened discussion
      on the restoration of facial deformities by allotransplantation. The authors
      introduce a hemifacial allograft transplant model to investigate the rationale
      for the development of functional tolerance across the major histocompatibility
      complex barrier. Eighteen rats in three groups were studied. The composite
      hemifacial allotransplantations including the ear and scalp were performed
      between Lewis-Brown Norway (RT1l+n) and Lewis (RT1l) rats and isotransplantations
      were performed between Lewis rats. Isograft controls (n = 6) and allograft
      controls (n = 6) did not receive treatment. Allografts in treatment group (n = 6)
      were treated with cyclosporine A 16 mg/kg/day during the first week; this dose
      was tapered to 2 mg/kg/day over 4 weeks and maintained at this level thereafter.
      Functional tolerance to face allografts was evaluated clinically and
      histologically. Donor-specific chimerism was assessed at days 21 and 63 by flow
      cytometry. In vitro evaluation of donor-specific tolerance was performed by mixed
      lymphocyte reaction at day 160 after transplantation. Isograft controls survived
      indefinitely. All nontreated allografts were rejected within 5 to 7 days after
      transplantation, as confirmed by histopathologic analysis. Five of six face
      allografts under the cyclosporine A protocol showed no signs of rejection for up
      to 240 days and remained alive and under evaluation, whereas one animal showed
      signs of rejection at day 140. This was reversed by adjustment of the
      cyclosporine A dose. At day 21 after transplantation, flow cytometric analysis of
      the donor-specific chimerism showed 1.11 percent of double-positive CD4FITC/RT1Ac
      Cy7 and 1.43 percent of double-positive CD8PE/RT1Ac-Cy7 T-cell populations in the
      peripheral blood of hemiface allotransplant recipients. The chimerism level of
      double-positive CD4FITC/RT1Ac-Cy7 T cells increased to 3.39 percent, whereas it
      remained stable for the double-positive CD8PE/RT1Ac-Cy7 T-cell population at day
      63 after transplantation (1.00 percent). The mixed lymphocyte reaction assay at
      day 160 after transplantation revealed donor-specific tolerance to donor (Lewis
      Brown Norway) antigens and strong reactivity to the third-party (ACI)
      alloantigens. In this study, donor-specific chimerism and functional tolerance
      were induced in hemifacial allograft transplants across the major
      histocompatibility complex barrier under cyclosporine A monotherapy protocol.
      This model will allow further studies on tolerance induction protocols.

PMID- 15577351
TI  - Anti-CD40 ligand antibody permits regeneration through peripheral nerve
      allografts in a nonhuman primate model.
AB  - Systemic immunosuppression is typically required to prevent allograft rejection.
      Antibody-based therapies that induce immune unresponsiveness represent an
      appealing alternative to nonspecific immunosuppression, which is often associated
      with significant morbidity. In mice, successful prevention of nerve allograft
      rejection has been demonstrated through interference with the CD40/CD40 ligand
      interaction. This study investigated the effectiveness of anti-CD40 ligand
      monoclonal antibody as single-agent therapy in preventing rejection and
      supporting nerve regeneration across long nerve allografts in nonhuman primates.
      Twelve outbred cynomolgus macaques were arranged into six genetically mismatched
      pairs, with each animal receiving a 5-cm ulnar nerve allograft in the right arm
      and a 5-cm autograft in the left arm. Mixed lymphocyte reaction assays were used
      to assess resulting immune unresponsiveness. Treated animals (n = 10) received
      anti-CD40 ligand monoclonal antibody 10 mg/kg one time, locally applied, and 20
      mg/kg systemically on postoperative days 0, 1, 3, 10, 18, and 28, and then
      monthly. Untreated animals (n = 2) served as the untreated controls. At 4 or 6
      months after transplantation, nerves were harvested for histological analysis.
      Four treated animals underwent an additional challenge after cessation of anti
      CD40 ligand monoclonal antibody therapy and nerve graft harvests. Autogenous and
      allogeneic skin and nerve inlay grafting was performed to assess the permanence
      of immune unresponsiveness induced by anti-CD40 ligand monoclonal antibody.
      Animals that received anti-CD40 ligand monoclonal antibody demonstrated robust
      regeneration across nerve allografts, similar to that seen in the autograft
      control in the contralateral arm. The histomorphometric analysis of allografts in
      the untreated animals demonstrated significantly worse measurements compared with
      their matched autograft controls. Animals that received anti-CD40 ligand
      monoclonal antibody with concomitant skin allografts had virtually no evidence of
      nerve regeneration through allografts. Allogeneic skin and nerve allografts
      applied 2 to 12 months after withdrawal of anti-CD40 ligand monoclonal antibody
      therapy were consistently rejected. This study demonstrates that anti-CD40 ligand
      monoclonal antibody prevents rejection and allows regeneration of peripheral
      nerve allografts in nonhuman primates. The effect of anti-CD40 ligand monoclonal
      antibody appears to be transient, however, with restoration of immunocompetence
      shortly after withdrawal of therapy.

PMID- 15577353
TI  - Quantitative transcriptional analysis of fusing and nonfusing cranial suture
      complexes in mice.
AB  - Previous studies have documented the differences in expression of various genes
      associated with the process of osteogenesis in fusing and nonfusing cranial
      sutures, including growth factors, growth factor receptors, and extracellular
      matrix molecules. Most of these studies were performed in rats, and although the
      biology regulating cranial suture fusion in mice and rats is presumed to be
      similar, studies are needed to verify these expression patterns as mice become
      increasingly utilized for scientific inquiry into the molecular biology of suture
      fusion and patency. The purpose of this study was to determine the differences in
      expression of several genes known to be critical to osteoblast biology. Posterior
      frontal and sagittal suture complexes (including the associated dura mater,
      suture mesenchyme, and osteogenic fronts) were isolated from 5-, 15-, 25-, 35-,
      and 45-day-old male CD-1 mice (n = 8 per age; n = 40 total). Total cellular RNA
      was extracted and converted to cDNA. Quantitative real-time reverse transcriptase
      polymerase chain reaction was then performed for the following genes:
      transforming growth factor beta1 and beta3, fibroblast growth factor receptor 1,
      Runx2,Osteopontin, and Osteocalcin. Expression of all genes examined was
      increased significantly in the posterior frontal suture as compared with the
      sagittal suture. Peak expression for all genes was observed on day 25. These data
      demonstrate that the expression of osteogenic growth factors, growth factor
      receptors, transcription factors, and extracellular matrix molecules is increased
      in the fusing posterior frontal suture in mice.

PMID- 15577354
TI  - Orbital floor reconstruction using calcium phosphate cement paste: an animal
      study.
AB  - Orbital floor defects were created in 10 New Zealand white rabbits and were
      reconstructed using an injectable calcium phosphate paste. These animals were
      euthanized at 2, 4, 8, and 12 months after implantation and were examined for
      biocompatibility and osteoconductivity. Grossly, implants were found to be
      adherent to the floor and covered with fibrous tissues. There was no sign of
      infection, extrusion, or migration of implant within the orbit and maxilla. The
      orbital floor was completely restored. Histological examination showed active new
      bone formation that encroached within the implant and gradually increased in
      density with time. Maxillary mucosa and glands were likewise reconstituted. Thin
      fibrovascular tissues were seen on top of and within the surface of the implant,
      and few to slight inflammatory cells were seen. Microradiography showed direct
      apposition between the new bone and the implant. These findings compare favorably
      with previously published reports on the biocompatibility and osteoconductivity
      of calcium phosphate cement. The authors believe that, together with ease of use
      and structural integrity, calcium phosphate paste can be useful in orbital floor
      reconstruction.

PMID- 15577355
TI  - Reduction of skeletal muscle injury in composite tissue allotransplantation by
      heat stress preconditioning.
AB  - Ischemia-reperfusion injury is a dominant factor limiting tissue survival in any
      microsurgical tissue transplantation, a fact that also applies to allogeneic hand
      transplantation. The clinical experience of the 12 human hand transplantations
      indicates that shorter ischemia times result in reduced tissue damage and,
      ultimately, in better hand function. Heat stress preconditioning and the
      accompanying up-regulation of the heat shock protein 72 have been shown to reduce
      the ischemia-reperfusion injury following ischemia of various organs, including
      organ transplantation. The aim of this study was to reduce the ischemia
      reperfusion injury in a model of composite tissue allotransplantation. Allogeneic
      hind limb transplantations were performed from Lewis (donor) to Brown-Norway
      rats. Donor rats in group A (n = 10) received a prior heat shock whereas rats in
      group B (n = 10) did not receive any prior heat shock. Group C served as a
      control group without transplantation. The transplantations were performed 24
      hours after the heat shock, at which time the heat shock protein 72 was shown to
      be up-regulated. The outcome was evaluated 24 hours after transplantation by
      nitroblue tetrazolium staining and wet-to-dry weight ratio of muscle slices
      (anterior tibial muscle). The nitroblue tetrazolium staining showed a significant
      reduction of necrotic muscle in group A (prior heat shock) (p = 0.005). The wet
      to-dry ratio was significantly reduced in group A (prior heat shock), indicating
      less muscle edema and less tissue damage (p = 0.05). Heat shock preconditioning
      24 hours before an ischemic event leads to an up-regulation of heat shock protein
      72 in muscle and to a tissue protection reducing ischemia-reperfusion injury in
      composite tissue transplantation.

PMID- 15577356
TI  - Modified separation of parts as an intervention for intraabdominal hypertension
      and the abdominal compartment syndrome in a swine model.
AB  - Standard therapy for abdominal compartment syndrome is laparotomy. In many
      patients, laparotomy involves a recent incision; for others, volume of
      resuscitation may be the cause. The components separation technique allows
      difficult abdominal closure. The authors studied the effect of a modified
      separation of parts on abdominal compartment syndrome in an animal model. Eight
      pigs were instrumented for measurement of central venous pressure, mean arterial
      pressure, peak airway pressure, and intraabdominal pressure. Intraabdominal
      hypertension to 25 mmHg was established with intraperitoneal fluid infusion.
      Modified separation of parts was performed by sequential release of the abdominal
      wall layers. With increased intraabdominal pressure, mean arterial pressure (55.3
      +/- 12.0 to 65.3 +/- 11.0), central venous pressure (7.7 +/- 2.4 to 13.3 +/-
      6.9), and peak airway pressure (20.2 +/- 2.4 to 25.3 +/- 4.1; p < 0.05) also
      increased. Maximum intraabdominal pressure was 26.0 +/- 1.2 mmHg. Skin incision
      resulted in a decrease in intraabdominal pressure to 21.7 +/- 4.5, external
      oblique release to 18.3 +/- 3.9, internal oblique release to 13.2 +/- 4.0, and
      transversus muscle incision to 7.0 +/- 2.5 mmHg (p < 0.05). With completion of
      components separation, mean arterial pressure remained increased (63.2 +/- 16.9),
      central venous pressure decreased (6.8 +/- 3.6; p < 0.05), and peak airway
      pressure decreased (22.7 +/- 3.9; p < 0.05). Modified separation of parts
      technique effectively releases intraabdominal hypertension and reverses the
      physiologic derangements associated with abdominal compartment syndrome in the
      animal model.

PMID- 15577357
TI  - A quantitative method for determining polarization of neutrophil adhesion
      molecules associated with ischemia reperfusion.
AB  - Ischemia-reperfusion-induced neutrophil adhesion to endothelium is CD18
      dependent, but information regarding polarity of CD18 adhesion molecules remains
      speculative. This study evaluated neutrophil adhesion using an in vitro cell
      adhesion assay and introduces a quantitative method of measuring CD18 membrane
      distribution using confocal microscopy. Neutrophils from normal animals were
      isolated from whole blood and incubated with plasma from rat gracilis muscle
      flaps with no ischemia and reperfusion (nonischemic control, n = 10) or 4 hours
      of ischemia and 90 minutes of reperfusion (ischemia/reperfusion, n = 10), on
      coverslips pretreated with and without (phosphate-buffered saline) soluble
      intercellular adhesion molecules. Coverslips without intercellular adhesion
      molecules represented a negative control (intercellular adhesion molecules were
      required for adhesion). Percent adherence to intercellular adhesion molecules was
      expressed as a ratio of adherent cells/total cells. CD18 polarization was
      assessed by staining neutrophils with fluorescein isothiocyanate-labeled anti
      CD11b, followed by confocal microscopy and Z-stack analysis. Membrane-associated
      CD18 was expressed as fluorescence intensity units in three equal areas of the
      cell membrane. Capping was defined as twice as much fluorescence in 33 percent of
      the cell membrane as in the remaining 67 percent. Neutrophils exposed to ischemia
      and reperfusion plasma showed a significant increase in adhesion (0.8 +/- 0.1
      percent versus 16.7 +/- 2.2 percent, p < 0.001) and CD18 polarization (6.2 +/-
      1.7 percent versus 43.9 +/- 12.2 percent, p = 0.0206) compared with controls.
      This article describes an in vitro assay that reliably reproduces the neutrophil
      adhesion phenomenon associated with ischemia-reperfusion injury. Results from
      confocal microscopy allowed for quantitative estimation of membrane-associated
      receptor polarization.

PMID- 15577358
TI  - Development of a modeling and osteotomy jig system for reconstruction of the
      mandible with a free vascularized fibula flap.

PMID- 15577359
TI  - Nonunion of the clavicle: a rare indication for vascularized free fibula
      transfer.

PMID- 15577360
TI  - A new approach to closure of large lumbosacral myelomeningoceles: the superior
      gluteal artery perforator flap.

PMID- 15577362
TI  - Revisiting the serratus anterior rib flap for composite tibial defects.

PMID- 15577363
TI  - The effect of the Accreditation Council for Graduate Medical Education Duty Hours
      Policy on plastic surgery resident education and patient care: an outcomes study.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) Work-Hours Duty
      Policy became effective on July 1, 2003, mandating the reduction of resident duty
      work hours. The Baylor College of Medicine Multi-Institutional Integrated Plastic
      Surgery Program instituted a resident duty work-hours policy on July 1, 2002 (1
      year ahead of the national mandate). Outcomes data are needed to facilitate
      continuous improvements in plastic surgical residency training while maintaining
      high-quality patient care. To assess the effect of this policy intervention on
      plastic surgery resident education as measured through the six core competencies
      and patient/resident safety, the investigators surveyed all categorical plastic
      surgery residents 6 months after implementation of the policy. This work
      represents the first empiric study investigating the effect of duty hours
      reduction on plastic surgery training and education. The categorical plastic
      surgery residents at the Baylor College of Medicine Multi-Institutional
      Integrated Plastic Surgery Program completed a 68-item survey on a five-point
      Likert scale (1 = strongly disagree to 5 = strongly agree). Residents were asked
      to rate multiple parameters based on the ACGME six core competencies, including
      statements on patient care and clinical/operative duties, resident education,
      resident quality of life, and resident perceptions on this policy. All surveys
      were completed anonymously. The sample size was n = 12 (program year 3 through
      program year 6), with a 100 percent response rate. Univariate and bivariate
      statistical analysis was conducted with SPSS version 10.0 statistical software.
      Specifically, interquartile deviations were used to find consensus among resident
      responses to each statement. Descriptive statistics indicated higher percentages
      of agreement on a majority of statements in three categories, including patient
      care and clinical/operative duties, academic duties, and resident quality of
      life. Using interquartile deviation, the highest levels of consensus among the
      residents were found in positive statements addressing resident alertness (both
      in and out of the operative environment), time to read/prepare for
      cases/conferences, efficacy of the didactic curriculum, and overall satisfaction
      with this policy for surgery resident education. Residents also felt that their
      patients favored this work hours policy. In addition, there was high consensus
      that this policy improved overall patient care. The majority of residents
      identified a negative effect of this policy through an increase in cross-coverage
      responsibilities, however, and half of the residents perceived that faculty
      negatively viewed their unavailability postcall. In addition, no consensus among
      the residents was achieved regarding perceptions on overall weekly operative
      experience. Plastic surgery residents perceived that the reduction of resident
      work hours through adherence to the ACGME guidelines has beneficial effects on
      patient care and clinical/operative duties, academic duties, and resident quality
      of life. Residents felt, however, that these benefits may increase cross-coverage
      workloads. Furthermore, residents were concerned about faculty perception of
      their changes in postcall duties. In contrast to previously published findings in
      the general surgery literature, the current results indicate that residents do
      not believe that this policy negatively affects continuity of patient care. In
      fact, the current findings suggest that adherence to this policy improves patient
      care on multiple levels. The effect on the operative experience remains to be
      elucidated. Further large-scale and longitudinal research design and analysis is
      warranted to better assess the results of the ACGME resident duty work-hours
      policy in plastic surgery resident education.

PMID- 15577364
TI  - Obesity in America: an increasing challenge for plastic surgeons.

PMID- 15577365
TI  - Temporary management of upper lid ptosis, lid malposition, and eyelid fissure
      asymmetry with botulinum toxin type A.
AB  - During the past 10 years the primary focus for the aesthetic use of botulinum
      toxin has been directed to the treatment of dynamic facial lines. This agent has
      been shown to be very effective for the improvement of facial shape. The use of
      botulinum toxin type A for the correction of a variety of presentations of facial
      asymmetry has also been well established. The general principles regarding the
      counter-effects of facial muscle protagonists and antagonists and their potential
      effects on the position of facial soft-tissue regions apply here as well. Twenty
      two patients received botulinum toxin type A for the temporary treatment of mild
      to moderate unilateral upper eyelid ptosis and aesthetic improvement of lower
      eyelid position, with favorable results. Although commonly related to a rare yet
      feared adverse consequence from the inappropriate application of botulinum toxin,
      its application for the treatment of upper eyelid ptosis, eyelid position, and
      other lid fissure asymmetries for aesthetic improvement is presented.

PMID- 15577366
TI  - The mystery of the split earlobe.
AB  - The ancient art of body piercing has rejuvenated in the recent years as part of
      the fashion process. The ear is the most frequent body part to be pierced to wear
      jewelry. Split earlobes are commonly presented to plastic surgeons and the
      recurrence rate is high. The etiology of the acquired split earlobe was thought
      to be attributable to either trauma or heavy earrings. In this study, the authors
      explored the cause of the split earlobe and recurrence after surgical repair.
      Twenty-five patients who were using gold earrings presented with split earlobe
      and were studied, and the etiology of the condition was analyzed. A questionnaire
      was completed and the tissue obtained during surgical repair of the split
      earlobes was submitted for histopathological studies. This group of patients was
      compared with 17 subjects having stretched earlobe who were using heavy gold
      earrings. The control group consists of 50 subjects using gold earrings with
      normal earlobes. Clinical presentation and the histological studies suggest that
      allergy to metals used in the earring could lead to split earlobe. There is a
      difference between the split earlobe and stretched earlobe; the latter results
      from constant pull by heavy earrings. The authors present a new theory regarding
      the etiology of split earlobe and recommend that avoiding the offending metal in
      the earring is indispensable to prevent recurrence.

PMID- 15577367
TI  - Locally administered ketorolac and bupivacaine for control of postoperative pain
      in breast augmentation patients.
AB  - With recent developments in the field of analgesia, the question arises whether
      there is a role for placing local anesthetics, nonsteroidal anti-inflammatory
      drugs, or both into the breast implant pocket. The objective of this study was to
      test the effectiveness of locally administered intraoperative ketorolac and
      bupivacaine with epinephrine at reducing pain in the postoperative period. The
      study was a prospective, randomized, double-blind clinical trial. One hundred
      consecutive retropectoral breast augmentation patients were enrolled, and
      informed consent was obtained. A standard anesthetic protocol and surgical
      procedure were followed. Normal saline, ketorolac alone (30 mg), bupivacaine
      alone (150 mg), or ketorolac and bupivacaine (30 mg and 150 mg respectively) were
      placed into the implant pocket before implant insertion. All patients completed
      the study. The power of this study to detect a 20 percent difference with respect
      to the primary outcome was 0.90 and confidence intervals of 95 percent were used
      to determine significance. The primary outcome was pain as measured by the visual
      analogue pain scale. The secondary outcome was time spent in the recovery room.
      Intraoperative placement of ketorolac combined with bupivacaine reduced pain in
      the postoperative period. It did not appear that anesthesiologist, anesthesia
      time, surgeon, operating room time, difficulty of dissection, breast incision, or
      implant size had a significant effect on postoperative pain. There was a trend
      that the ketorolac and bupivacaine patients spent less time in the recovery room
      and used fewer analgesics postoperatively than the other patients. There were no
      hematomas requiring reoperation and no complications. Locally administered
      intraoperative ketorolac and bupivacaine with epinephrine significantly reduced
      pain in the postoperative period.

PMID- 15577368
TI  - Optimizing body contour in massive weight loss patients: the modified vertical
      abdominoplasty.
AB  - In morbid obesity, contour deformities of the abdomen are common after bariatric
      surgery and radical weight loss. Traditional abdominoplasty techniques often fail
      to maximally improve body contour in these cases because adjacent sites such as
      the hip rolls and flanks are not treated, leaving the patient with large lateral
      tissue redundancies and dog-ears. In an attempt to solve these challenging
      problems, the authors present the modified vertical abdominoplasty technique, a
      single-stage procedure that involves a combined vertical and transverse approach
      in which an "en bloc" resection of the redundant tissues is performed without
      undermining, drainage, or reinforcement of the abdominal wall. The latter is only
      carried out when diastasis and/or hernias are present, and Marlex mesh may be
      utilized when indicated. In patients with simultaneous large umbilical hernias
      and/or excessively long stalks, neoumbilicoplasty is recommended. A significant
      improvement of abdominal contour was obtained in the vast majority of patients
      because the resection design offers simultaneous treatment of both vertical and
      transverse tissue redundancies in the abdomen and neighboring regions, with more
      harmonic results when compared with purely vertical or transverse approaches. The
      modified vertical abdominoplasty technique is an easy, fast, and reliable
      alternative for treating these patients, with less intraoperative bleeding,
      reduced overall cost, and low morbidity rates. In selected cases, the technique
      is capable of offering excellent results in terms of contouring and maximizes the
      overall outcome of treatment protocols for these patients, who can then be
      integrated into normal life with heightened self-esteem, happiness, and
      productivity.

PMID- 15577370
TI  - Mental health histories and psychiatric medication usage among persons who sought
      cosmetic Surgery.
AB  - This retrospective chart review study examined the mental health histories and
      psychiatric medication usage of persons who sought cosmetic surgery. The medical
      records of 232 patients who had undergone a consultation for a cosmetic procedure
      were reviewed. The rates of self-reported psychiatric disorders and of
      psychiatric medication usage of these patients were compared with those of 200
      patients who underwent noncosmetic procedures. Nineteen percent of cosmetic
      surgery patients reported a mental health history, significantly greater than the
      4 percent of the noncosmetic patients who reported a psychiatric history.
      Eighteen percent of the cosmetic patients reported using a psychiatric medication
      at the time of their consultation, also significantly greater than the 5 percent
      of the noncosmetic patients who reported psychiatric medication usage. These
      results underscore the importance of collecting a psychiatric history from
      prospective cosmetic surgery patients. Recommendations for assessing patients'
      psychiatric history and status are provided.

PMID- 15577372
TI  - Rhinoplasty with advancing age.
AB  - Rhinoplasty in the aging patient poses a unique set of challenges to the plastic
      surgeon. Aging patients usually have different expectations and motivations than
      their younger counterparts; therefore, open communication and frank discussions
      are paramount to define realistic goals. Anatomically, changes in skin quality,
      cartilage characteristics, underlying bony framework, and the nasal airways
      mandate special considerations to optimize the functional and aesthetic results.
      This review will present a practical approach to the management of the nose in
      the aging patient.

PMID- 15577373
TI  - The key to long-term success in liposuction: a guide for plastic surgeons and
      patients.
AB  - Patients need to have realistic expectations for a long-term successful body
      contour result. There are four key elements for long-term successful improvement
      in body contour, and the patient is responsible for the first three: exercise, a
      proper diet, and other positive lifestyle changes; and successful body
      contouring. An extensive survey requesting information about the procedures,
      areas of liposuction, lifestyle habits, and satisfaction was mailed to 600
      patients who had liposuction surgery performed between 1999 and 2003. One hundred
      and eight surveys were undeliverable and 209 completed surveys were returned
      (34.8 percent of 600 mailed surveys and 42.5 percent of 492 delivered surveys).
      Data were analyzed by a binary logistic regression with backward elimination.
      Weight gain (versus no weight gain) was used as the dependent variable. The
      results showed that regardless of whether the patient did or did not gain weight,
      both groups reported being very satisfied (30 percent and 48 percent,
      respectively) or satisfied (43 percent and 34 percent, respectively) with their
      procedure. Among the weight gain patients, 72 percent would still have the
      procedure again, compared with 82 percent of responders who did not gain weight.
      When asked if they would recommend the procedure to family or friends, 90 percent
      of responders who did not gain weight would recommend the procedure whereas only
      74 percent of responders who did gain weight would recommend the procedure (p <
      0.001). Among those patients who gained weight, only 29 percent thought their
      appearance was excellent or good (compared with 79 percent of those who did not
      gain weight). Among the 57 percent of patients who did not gain weight, 35
      percent report exercising more postoperatively (compared with only 10 percent in
      the weight gain group, p = 0.002) and 50 percent report eating a healthier diet
      (22 percent in the weight gain group report eating a healthier diet, p = 0.002).
      In the weight gain group, 67 percent report no change in their diet regimen and
      only 17 percent thought their productivity increased (compared with 25 percent
      among the no weight gain group, p = 0.002). Successful body contouring surgery
      requires a patient to embrace positive lifestyle habits. The results of this
      survey have been used to create a quantitative decision-making framework or a
      "road map" for patients and plastic surgeons to use for navigating toward
      successful long-term results.

PMID- 15577375
TI  - Plasmetic surgery.

PMID- 15577376
TI  - Plastic surgery as "show biz".

PMID- 15577378
TI  - Metastases to the donor site of the pectoralis major myocutaneous flap following
      reconstructive surgery: a rare complication.

PMID- 15577379
TI  - Unfavorable findings following breast augmentation using injected polyacrylamide
      hydrogel.

PMID- 15577380
TI  - Successful pregnancy after breast reconstruction with the deep inferior
      epigastric perforator flap.

PMID- 15577381
TI  - "Power drill radiator".

PMID- 15577382
TI  - Hybrid mattress suture.

PMID- 15577383
TI  - An interesting, smart, and useful device during removal of fat grafts in office
      based conditions: towel clamps.

PMID- 15577384
TI  - A simple method of locking the plunger during syringe liposuction.

PMID- 15577385
TI  - Obtaining predictable results in malar augmentation with preimplant fat
      injection.

PMID- 15577386
TI  - Neurothekeoma palpebrae.

PMID- 15577387
TI  - Infant with a protruding mass on the chin.

PMID- 15577388
TI  - Heavy-duty workers of the medical art oppose digital image systems.

PMID- 15577389
TI  - Increasing the accuracy of sterile marker pens.

PMID- 15577390
TI  - A novel use of the Rhys-Davies exsanguinator.

PMID- 15577391
TI  - Effects of lipoic acid and a reduced-calorie diet on skin flap survival in a rat
      model.

PMID- 15577392
TI  - Axillary giant lipoma.

PMID- 15577393
TI  - Giant compressing lipoma of the thigh.

PMID- 15577394
TI  - Neural fibrolipoma of the foot.

PMID- 15577395
TI  - Posttraumatic fingertip lipoma.

PMID- 15577396
TI  - Development of pseudolipoma after an endoscopically confirmed closed degloving
      injury.

PMID- 15577397
TI  - The surgical workforce crisis.

PMID- 15577399
TI  - Surgical residency and foreign medical graduates.

PMID- 15577401
TI  - International medical graduates.

PMID- 15577402
TI  - The role of women in the surgical workforce.

PMID- 15577405
TI  - Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated
      reverse transcriptase from different HIV types and groups.
AB  - OBJECTIVES: To evaluate a phenotype assay based on plasma reverse transcriptase
      (RT) to assess HIV susceptibility to nonnucleoside RT inhibitors (NNRTIs). To
      compare RT-based phenotype with recombinant virus assay (RVA) phenotype- and
      genotype-based analysis. To assess group O and HIV-2 susceptibility to NNRTIs in
      correlation with genotype polymorphisms. METHODS: RT activity was quantified and
      its susceptibility to efavirenz, nevirapine, and delavirdine measured as drug
      concentration resulting in 50% inhibition. RT phenotype was compared with
      genotype analysis. Eighteen plasma samples from 14 group M- and culture
      supernatants from 4 group M-, 9 group O-, and 7 HIV-2-infected patients were
      investigated. RT-based and RVA-based phenotypes were compared for identical
      plasma from 9 group M-infected patients. RESULTS: RT-based and RVA-based
      phenotypes were in complete agreement. RT-based phenotype- and genotype-predicted
      susceptibility were concordant for all but 1 group M samples. One plasma showed
      susceptibility to 3 NNRTIs by phenotypes, despite the presence of 101E and 106I/V
      residues. The HIV-2 RTs were totally resistant to the NNRTIs tested. Among HIV-1
      group O, 6 were totally resistant to NNRTIs independently of the presence of the
      181C mutation and 3 were susceptible to some NNRTIs. CONCLUSION: Plasma RT-based
      phenotype could be useful as a simple alternative for monitoring resistance to
      NNRTIs. This assay is suitable for highly divergent strains. It would be
      particularly useful for large epidemiologic survey of the natural HIV
      polymorphism and the potential impact in emergence of drug resistance,
      particularly to nevirapine, widely used to prevent mother-to-child transmission.

PMID- 15577406
TI  - Upregulatory mechanisms compensate for mitochondrial DNA depletion in
      asymptomatic individuals receiving stavudine plus didanosine.
AB  - Nucleoside analogue use is often related to mitochondrial DNA (mtDNA) depletion,
      but mitochondrial function is preserved in most asymptomatic patients. We
      determined whether homeostatic mechanisms are able to compensate for this mtDNA
      depletion in patients receiving stavudine plus didanosine (d4T + ddI), an
      antiretroviral combination with great in vitro and in vivo capacity to decrease
      mtDNA. We included 28 asymptomatic HIV-infected individuals: 17 subjects (cases)
      on a first-line antiretroviral regimen consisting of d4T + ddI as the nucleoside
      backbone plus nevirapine or nelfinavir for at least 6 months (mean: 16 +/- 8
      months) and 11 naive subjects (controls). We assessed the following in peripheral
      blood mononuclear cells: mitochondrial mass by citrate synthase activity, mtDNA
      content by real-time polymerase chain reaction, cytochrome c oxidase subunit II
      (COX-II) expression by Western blot analysis, and COX activity by
      spectrophotometry. The mitochondrial mass and mtDNA content of cases decreased
      when compared with controls, whether normalized per cell or per mitochondrion.
      Conversely, COX-II expression and COX activity were similar in cases and
      controls. COX-II expression was constant and independent of the mtDNA content,
      whereas it was closely related to COX activity. We concluded that treatment with
      dd4T + ddI is associated with decreased mitochondrial mass and mtDNA content but
      that COX-II expression and COX activity remain unaltered. These data suggest that
      upregulatory transcriptional or posttranscriptional mechanisms compensate for
      mtDNA depletion caused by d4T + ddI before profound mtDNA depletion occurs.

PMID- 15577407
TI  - Nelfinavir induces necrosis of 3T3F44-2A adipocytes by oxidative stress.
AB  - Protease inhibitor treatment strongly diminishes mortality in HIV-infected
      patients. This treatment has also been associated with lipodystrophy and has been
      shown to alter adipocyte differentiation. The protease inhibitor nelfinavir has
      been indirectly implicated in the appearance and development of lipodystrophic
      syndrome, as well as in adipocyte cell death. The aim of this study was to
      evaluate the effects of nelfinavir on the 3T3-F442A adipocyte cell line.
      Nelfinavir (30 microM) induced cell death of 3T3-F442A adipocytes by a necrotic
      process that was not mediated by TNF-alpha. Treatment of cells with this protease
      inhibitor led to a significant increase in expression of the heme oxygenase-1
      gene that could be reduced by 100 microM of the antioxidant ascorbate. Moreover,
      ascorbate had a protective effect on nelfinavir-induced necrosis, decreasing the
      percentage of necrotic cells by 70%. Our results show that nelfinavir induces
      necrosis of adipocytes mediated by a cellular increase of reactive oxygen
      species. This deleterious effect could be counterbalanced by ascorbate.

PMID- 15577408
TI  - HIV-associated anal cancer: has highly active antiretroviral therapy reduced the
      incidence or improved the outcome?
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced the
      incidence and improved the survival of patients with Kaposi sarcoma and AIDS
      related non-Hodgkin lymphoma. We wished to evaluate its effects on incidence and
      survival in HIV-associated anal cancer. METHODS: We measured the incidence and
      survival of patients with invasive anal cancer from our prospective cohort of
      8640 HIV-seropositive individuals. RESULTS: In our cohort of 8640 HIV
      seropositive individuals, the incidence of invasive anal cancer (diagnosed in 26
      patients) is 60 per 100,000 patient-years. This is 120 times higher than in the
      age- and gender-matched general population. The incidence of invasive anal cancer
      in the HIV cohort was 35 (95% confidence interval CI: 15-72) per 100,000 patient
      years of follow-up in the pre-HAARTera (1984-1995) and 92 (95% CI: 52-149) per
      100,000 patient-years of follow-up in the post-HAARTera (1996-2003) (P > 0.05).
      These figures are significantly higher than those for the general population (P <
      0.001 for both) and give a relative risk of 67 and 176 in the pre- and post-HAART
      eras, respectively, compared with the general population. The 5-year overall
      survival is 47% (95% CI: 24%-70%), and the 5-year disease-free survival is 66%
      (95% CI: 45%-87%). There is no difference in overall survival between the pre-
      and post-HAART eras (log rank P = 0.19). CONCLUSIONS: Unlike other HIV-associated
      cancers, there has been no significant change in the incidence, clinical
      features, or overall survival since the introduction of HAART.

PMID- 15577409
TI  - Effectiveness of generic fixed-dose combinations of highly active antiretroviral
      therapy for treatment of HIV infection in India.
AB  - OBJECTIVE: To assess clinical and immunologic effectiveness and acute toxicity to
      nevirapine (NVP)-based fixed-dose combinations (FDCs) in antiretroviral-naive HIV
      1-infected patients in India. DESIGN: Observational study of patients initiated
      on NVP-based combination therapy delivered as FDCs. METHODS: Antiretroviral-naive
      HIV-1-infected patients initiated on FDCs (zidovudine/lamivudine [3TC]/NVP or
      stavudine/3TC/NVP) were assessed clinically and with CD4 counts periodically.
      Adverse events to NVP were assessed clinically and by laboratory markers.
      Frequency and risk factors for development of adverse events and clinical
      outcomes were determined. RESULTS: Of the 1291 patients started on therapy, 1253
      completed a minimum of 3 months of follow-up. Rash and hepatitis were documented
      in 6.6% (95% confidence interval [CI]: 5.5-8.3) and 3.2% (95% CI: 2.3-4.8) of
      patients initiating therapy, respectively. There was significant improvement in
      CD4 counts over 2 years. Fourty-eight patients died, and 186 clinical events were
      documented in these patients. Tuberculosis was the most common cause of morbidity
      and mortality. Self-reported adherence was high. CONCLUSION: Fixed-dose
      formulations of NVP-based combination therapy are safe and produced durable
      clinical and immunologic benefit.

PMID- 15577410
TI  - Long-term persistence of primary genotypic resistance after HIV-1 seroconversion.
AB  - Primary infection with drug-resistant HIV-1 is well documented. We have followed
      up patients infected with such viruses to determine the stability of resistance
      associated mutations. Fourteen patients who experienced primary infection with
      genotypic evidence of resistance were followed for up to 3 years. Drug resistance
      associated mutations persisted over time in most patients studied. In particular,
      M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and
      multidrug resistance demonstrated little reversion to wild-type virus. By
      contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9
      months, respectively. Multidrug resistance in 2 patients was found to be stable
      for up to 18 months, the maximum period studied. We conclude that certain
      resistance-associated mutations are highly stable and these data support the
      recommendation that all new HIV diagnoses in areas where primary resistance may
      occur should undergo genotyping irrespective of whether the date of
      seroconversion is known.

PMID- 15577411
TI  - Incidence of immune reconstitution syndrome in HIV/tuberculosis-coinfected
      patients after initiation of generic antiretroviral therapy in India.
AB  - This paper describes the incidence of immune reconstitution syndrome (IRS) from
      the developing world and implications for clinicians. Eleven of 144 HIV and
      tuberculosis (TB)-coinfected individuals followed for 72 person-years developed
      IRS within 6 months of initiating generic highly active antiretroviral therapy
      (HAART). All of the IRS patients were male, with a median age of 29 years; median
      CD4 at HAART initiation was 123 cells/mm3, and 6-month median CD4 rise was 124
      cells/mm3. There was no statistical difference in CD4 rise or CD4 count and
      duration of TB treatment at HAART initiation between those who did and those who
      did not develop IRS (P = 0.8380). The median time to development of clinical IRS
      was 42 days (range 10-89 days). The incidence of IRS in this cohort is 15.2 cases
      per 100 patient-years. With increased coprevalence of opportunistic infections,
      especially TB, and increasing access to antiretroviral therapy in the developing
      world, clinicians in these countries must be able to identify IRS and relieve
      symptoms without compromising clinical care.

PMID- 15577412
TI  - Protease inhibitor and nonnucleoside reverse transcriptase inhibitor
      concentrations in the genital tract of HIV-1-infected women.
AB  - The pharmacokinetics of antiretrovirals (ARVs) in the female genital tract (FGT)
      are likely to influence vertical and sexual transmission of HIV, the development
      of viral resistance, and post-exposure prophylaxis regimens. This study is the
      first to compare ARV concentrations in direct aspirates of cervicovaginal fluid
      (CVF) and blood plasma (BP). This unique method provides direct assessment of
      concentrations without the confounding of cervicovaginal lavage dilution. Of 8
      ARVs, CVF concentrations ranged from <10% to >100% of BP concentrations. These
      large differences in CVF penetration suggest that further research into ARV
      pharmacokinetics and drug efficacy in the FGT is necessary.

PMID- 15577413
TI  - Persistent antiretroviral activity of nucleoside analogues after prolonged
      zidovudine and lamivudine therapy as demonstrated by rapid loss of activity after
      discontinuation.
AB  - Antiretroviral (ARV) treatment decisions are difficult for HIV-1-infected
      patients on complex treatment regimens who have partial suppression of HIV-1
      replication and limited treatment options. Information on the ARV activity of the
      components of a complex regimen would be useful. Sixteen subjects who had
      received prolonged therapy with zidovudine (ZDV) and lamivudine (3TC), with a
      median duration of 32.5 months, were discontinuing this dual-nucleoside regimen
      and volunteered to have plasma HIV-1 RNA levels monitored over the 2 weeks after
      discontinuation. All subjects experienced an increase in HIV-1 RNA after
      discontinuation, with a median increase of 0.54 log10 copies/mL over 2 weeks
      (range: 0.31-1.71; P < 0.001). An inverse correlation existed between the decline
      in HIV-1 RNA levels over 2 to 3 years on nucleoside analogue therapy and the
      increase over the 10 to 14 days off therapy (Spearman r = -0.53; P = 0.036). Over
      the 2-week period, a subset of individuals who had genotype testing at multiple
      reverse transcriptase codons associated with ZDV and 3TC resistance had no
      changes in genotype off therapy. Nucleoside analogue reverse transcriptase
      inhibitors may have continued ARV activity despite long durations of partially
      suppressive therapy and the presence of resistant HIV-1.

PMID- 15577414
TI  - A randomized controlled trial of 5% lidocaine gel for HIV-associated distal
      symmetric polyneuropathy.
AB  - OBJECTIVE: To investigate the analgesic efficacy and safety of 5% lidocaine gel
      in painful HIV-associated distal sensory polyneuropathy (DSP). BACKGROUND:
      Painful DSP, the most common neurologic complication in HIV infection, is
      difficult to treat. Lidocaine 5% gel was effective in alleviating neuropathic
      pain in an open-label study of HIV DSP. METHODS: In a double-blind, placebo
      controlled, crossover, multi-center study, 64 subjects were randomized to receive
      5% lidocaine or vehicle gel for 2 weeks (phase A). A washout period of 2 weeks
      was followed by a crossover to the alternate agent for another 2 weeks (phase B).
      The primary outcome was difference in average pain scores (Gracely pain scale)
      between the 2 groups during the second week of each treatment period. Secondary
      outcomes included differential effect of the first treatment, difference in
      global pain relief, and pain response by neurotoxin exposure. RESULTS: The
      baseline pain scores of the 2 groups were similar. The average pain scores during
      the second week of each phase of the lidocaine gel group did not differ from
      those of the placebo group (phase A: lidocaine 1.09, placebo 1.15; phase B:
      lidocaine 1.16, placebo 1.10). There also was no difference noted in secondary
      outcomes. The pain responses of lidocaine gel-treated subjects with current
      exposure to neurotoxic antiretrovirals (1.18) did not differ compared with those
      without (1.10) (P = 0.358). There were no significant adverse effects.
      CONCLUSION: Lidocaine 5% gel is a safe but ineffective agent in the treatment of
      pain in HIV-associated DSP.

PMID- 15577415
TI  - Selection of antiretroviral therapy guided by genotypic or phenotypic resistance
      testing: an open-label, randomized, multicenter study (PhenGen).
AB  - The phenotype/genotype (PhenGen) open-label, randomized, multicenter study
      evaluated the genotype/virtual phenotype (vPt) and real phenotype (rPt) for
      choosing a new highly active antiretroviral therapy regimen at failure. Patients
      with a plasma viral load (pVL) between 2000 and 200,000 copies/mL and a CD4 cell
      count >200/microL, failing > or =2 regimens (<6 drugs), were randomized for vPt
      or rPt. Three hundred three patients were enrolled: 111 and 108 patients received
      a new treatment in the vPt and rPt arms, respectively. The 2 groups were
      comparable for baseline patient characteristics and treatment history. The new
      therapy was in agreement with expert advice in 58.5% of cases. After 6 months, no
      statistical differences were found in the mean absolute change from baseline CD4
      cells (+55 and +46 cells/muL; P = 0.7), mean pVL log decrease (-1.35 and -1.37; P
      = 0.8), or proportion of patients with a pVL <400 copies/mL (54.8% in vPt arm and
      52.6% in rPt arm; P = 0.9). At multivariate analysis, variables independently
      associated with failure of the new regimen were: pVL at baseline (odds ratio [OR]
      = 1.81; P < 0.021), number of nucleoside reverse transcriptase inhibitor
      associated mutations (OR = 1.21; P = 0.001), number of protease mutations (OR =
      1.15; P < 0.001), and recycling of indinavir (OR = 4.63; P = 0.019). Patients'
      adherence to the prescribed regimen (OR = 0.23; P < 0.001), number of active
      drugs in the new regimen (OR = 0.55; P = 0.001), and adherence to expert advice
      (OR = 0.37; P < 0.001) predicted virologic response. The vPt is as predictive of
      treatment outcome as the rPT. Use of expert advice significantly improved the
      response to therapy.

PMID- 15577416
TI  - The utility of a bone marrow biopsy in diagnosing the source of fever of unknown
      origin in patients with AIDS.
AB  - A bone marrow (BM) aspiration and biopsy is often believed to be a needed
      diagnostic procedure in the work-up of patients with fever of unknown origin
      (FUO), especially in the setting of AIDS. Is it worthwhile to proceed with this
      invasive diagnostic method? Clinical information obtained on 104 patients in whom
      AIDS had been previously diagnosed and who had been admitted with a presumptive
      diagnosis of FUO was retrospectively analyzed. Seventy-two cases met the
      inclusion criteria. A BM aspiration and biopsy had a low sensitivity as a
      diagnostic tool even in patients who had abnormal hematologic parameters. BM
      biopsy was also not helpful in diagnosing non-Hodgkin lymphoma (NHL) cases in
      this study. Although the incidence of NHL has risen since the emergence of HIV,
      the predominant types of lymphoma seen in AIDS patients are intermediate/high
      grade lymphomas rather than low grade, and consequently, the incidence of BM
      involvement is low, decreasing the sensitivity of a BM biopsy as a diagnostic
      tool. These observations were validated in this study. The majority of BM
      biopsies in this series revealed diagnostic features of infections. This
      observation can likely be related to the high prevalence of HIV/AIDS patients in
      this community and opportunistic infections associated with this disease.

PMID- 15577417
TI  - Herpes zoster in women with and at risk for HIV: data from the Women's
      Interagency HIV Study.
AB  - BACKGROUND: Herpes zoster occurs at all CD4 cell counts in HIV-infected adults.
      It was hypothesized that even in the era of highly active antiretroviral therapy
      (HAART), zoster risk is higher in HIV-infected than uninfected women. METHODS:
      Generalized estimating equations modeled self-reported occurrence of zoster
      between semiannual visits among 1832 HIV-infected and 489 HIV-uninfected women in
      the Women's Interagency HIV Study followed for up to 7.5 years. RESULTS: A total
      of 337 (18.4%) HIV-infected and 7 (1.4%) HIV-uninfected women reported zoster at
      some time during follow-up. Using HIV-infected women with CD4 >750 cells/microL
      as the reference category, the odds ratios for reporting zoster since the prior
      visit were: 1.43 (95% CI 0.86-2.37) for CD4 500-749 cells/microL, 2.07 (95% CI
      1.27-3.38) for CD4 350-499 cells/microL, 2.72 (95% CI 1.66-4.46) for CD4 200-349
      cells/microL, and 3.16 (95% CI 1.92-5.18) for CD4 <200 cells/microL, compared
      with 0.11 (95% CI 0.046-0.26) for HIV-uninfected women. In multivariate analyses
      using visits from all HIV-infected women and only those who initiated HAART,
      lower CD4 cell count was more strongly associated with zoster incidence than were
      other clinical indicators. CONCLUSIONS: Herpes zoster is associated with degree
      of immunosuppression in HIV-infected women, but even women with high CD4 counts
      are at greater risk of zoster than HIV-uninfected women.

PMID- 15577418
TI  - Measurement characteristics of anal cytology, histopathology, and high-resolution
      anoscopic visual impression in an anal dysplasia screening program.
AB  - BACKGROUND: The study aims were (1) to estimate agreement between consecutive
      anal cytologic examinations, between concurrent cytologic examination and
      histopathology, and between high-resolution anoscopy (HRA) visual impression and
      histopathology and (2) to estimate the prevalence of severe dysplasia by
      concurrent cytologic category. METHODS: Prospective study of HIV-infected
      patients receiving anal dysplasia screening as part of routine care. Agreement
      between measures was estimated by weighted kappa-statistics. RESULTS: Between
      July 2000 and September 2003, 1864 patients underwent 2947 anal cytology tests.
      Excluding unsatisfactory tests (6%), 642 patients had repeat cytologic evaluation
      and 154 had concurrent cytology tests and biopsy. Using 4-category cytology
      grading, kappa-agreement between the first 2 cytologic measurements was 0.36.
      Comparing concurrent cytology tests and biopsy, kappa-agreement was 0.36.
      Comparing the most severe HRA visual impression and biopsy, kappa-agreement was
      0.32. The prevalence of anal intraepithelial neoplasia 3 at biopsy by concurrent
      cytology category was 0 (cytology normal), 21% (atypical squamous cells of
      uncertain significance), 27% (low-grade squamous intraepithelial lesion), and 54%
      (high-grade squamous intraepithelial lesion). CONCLUSIONS: These data suggest
      that the reproducibility of key screening measures is moderate at best but of
      similar magnitude to that of other studies of anal and cervical dysplasia
      screening. As candidate interventions to treat or prevent precursor lesions enter
      clinical development, standardization and improvement of measurement methods are
      essential.

PMID- 15577419
TI  - HIV seroconversion among the homeless and marginally housed in San Francisco: a
      ten-year study.
AB  - HIV seroprevalence was previously found to be 9-11% among the urban homeless in
      San Francisco, with most infections among injection drug users, men who have sex
      with men, and those who exchange sex for money or drugs. In this study, HIV
      incidence and risk factors for seroconversion were estimated among persons who
      repeatedly participated in cross-sectional serosurveys over a period of 10 years.
      There were 6 seroconversions among 799 HIV-negative persons, for an incidence
      rate of 0.30% per person-year (95% CI: 0.12-0.61% per person-year). The
      seroconversion rate among men who had had recent sex with men was 1.22% per
      person-year (95% CI: 0.29-3.18) and was 0.52% per person-year (95% CI: 0.19-1.13%
      per person-year) among those who ever injected drugs. The seroconversion rate
      among those who were aged <30 years at baseline was 1.67% per person-year (95%
      CI: 0.40-4.36% per person-year), which was significantly higher than for those
      age > or =30 years. Policy implications are that HIV resources aimed at the more
      stable, older homeless population should probably focus on treatment, while
      prevention efforts, conversely, should probably be targeted to younger homeless
      persons.

PMID- 15577420
TI  - Antenatal couple counseling increases uptake of interventions to prevent HIV-1
      transmission.
AB  - To determine effect of partner involvement and couple counseling on uptake of
      interventions to prevent HIV-1 transmission, women attending a Nairobi antenatal
      clinic were encouraged to return with partners for voluntary HIV-1 counseling and
      testing (VCT) and offered individual or couple posttest counseling. Nevirapine
      was provided to HIV-1-seropositive women and condoms distributed to all
      participants. Among 2104 women accepting testing, 308 (15%) had partners
      participate in VCT, of whom 116 (38%) were couple counseled. Thirty-two (10%) of
      314 HIV-1-seropositive women came with partners for VCT; these women were 3-fold
      more likely to return for nevirapine (P = 0.02) and to report administering
      nevirapine at delivery (P = 0.009). Nevirapine use was reported by 88% of HIV
      infected women who were couple counseled, 67% whose partners came but were not
      couple counseled, and 45%whose partners did not present for VCT (P for trend =
      0.006). HIV-1-seropositive women receiving couple counseling were 5-fold more
      likely to avoid breast-feeding (P = 0.03) compared with those counseled
      individually. Partner notification of HIV-1-positive results was reported by 138
      women (64%) and was associated with 4-fold greater likelihood of condom use (P =
      0.004). Partner participation in VCT and couple counseling increased uptake of
      nevirapine and formula feeding. Antenatal couple counseling may be a useful
      strategy to promote HIV-1 prevention interventions.

PMID- 15577421
TI  - Diminished representation of HIV-1 variants containing select drug resistance
      conferring mutations in primary HIV-1 infection.
AB  - This study compared the incidence of HIV-1 variants harboring mutations
      conferring resistance to thymidine analogues, ie, thymidine analogue mutations
      (TAMs), nonnucleoside reverse transcriptase (RT) inhibitors (NNMs), lamivudine
      (3TC) (ie, M184V), and protease inhibitors (PIs) acquired in primary HIV
      infection (PHI) (n = 59) to their observed prevalence in a corresponding
      potential transmitter (PT) population of persons harboring resistant infections
      (n = 380). Both of these populations in the context of this cohort analysis
      possessed similar demographics. Whereas the frequencies of observed TAMs, NNMs,
      M184V, and protease-associated mutations (PRAMs) were similar in the PT groups,
      the prevalence of M184V and major PI mutations were significantly lower in the
      PHI group (PHI/PT ratios of 0.14 and 0.39, respectively). There was a decreased
      prevalence in the PHI population of resistant viruses co-expressing NNMs or TAMs
      with M184V compared with viruses that harbored NNMs or TAMs in the absence of
      M184V (P < 0.0001). It was also observed that individuals in the PT subgroups who
      harbored RT mutations or PRAMs with M184V had lower levels of plasma viremia than
      individuals who lacked M184V (P < 0.05). These findings suggest that both
      decreased viremia and viral fitness in the case of M184V-containing HIV-1
      variants may impact on viral transmissibility.

PMID- 15577422
TI  - Evaluation of four simple/rapid assays and two fourth-generation ELISAs for the
      identification of HIV infection on a serum panel representing the HIV-1 group M
      genetic diversity in Cameroon.
AB  - The performance of 4 rapid and simple assays: Camstix-HIV 1+2 (Camdiagnostix,
      Yaounde, Cameroon); Determine HIV 1+2+0 (Abbott Laboratories, Tokyo, Japan);
      Genie II HIV-1/HIV-2 (Bio-Rad, Marnes la Coquette, France); ImmunoComb II HIV 1 &
      2 BiSpot (Orgenics, Yavne, Israel); and 2 fourth-generation ELISAs: Enzygnost HIV
      Integral (Dade Behring, Marburg, Germany) and Genscreen plus HIV Ag-Ab (Bio-Rad,
      Marnes la Coquette, France) currently used in Cameroon to detect HIV infections
      were evaluated on a local serum panel. A total of 503 samples were collected,
      using the Camstix-HIV 1+2 assay. Overall, 280 samples were confirmed HIV
      positive, 181 were negative, and 42 were indeterminate. All positive samples
      belonged to group M: CRF02_AG (73.5%), A1 (7.1%), A2 (1.2%), G (4.7%), F2 (5.1%),
      D (1.6%), CRF11 (1.6%), CRF06 (1.2%), and CRF01_AE (1.6%). Sensitivity,
      specificity, test efficiency, and positive and negative predictive values were
      calculated both including and excluding indeterminate samples. Except for Genie
      II and ImmunoComb II (98.9 and 99.3%, respectively), sensitivities were 100% for
      the remaining 4 tests. Specificities, efficiencies, and positive predictive
      values of all assays were negatively affected by the addition of HIV
      indeterminate samples in the calculations. These data show the importance of
      prior test evaluations on local serum panels and in field conditions before a
      national policy for HIV screening is decided on and stress also the need to use
      tests and algorithms that can reduce the high number of HIV-indeterminate results
      in Africa.

PMID- 15577423
TI  - Genetic diversity of HIV type 1 in rural eastern Cameroon.
AB  - To monitor the presence of genotypic HIV-1 variants circulating in eastern
      Cameroon, blood samples from 57 HIV-1-infected individuals attending 3 local
      health centers in the bordering rural villages with Central African Republic
      (CAR) were collected and analyzed phylogenetically. Out of the 40 HIV-1 strains
      with positive polymerase chain reaction (PCR) profile for both gag and env
      C2V3,12 (30.0%) had discordant subtype or CRF designation: 2 subtype B/A
      (gag/env), 1 B/CRF01, 2 B/CRF02, 1 CRF01/CRF01.A, 2 CRF11/CRF01, 1 CRF13/A, 1
      CRF13/CRF01, 1 CRF13/CRF11, and 1 G/U (unclassified). Twenty-eight strains
      (70.0%) had concordant subtypes or CRF designation between gag and env: 27
      subtype A and 1 F2. Out of the remaining 17HIV-1 strains negative for PCR with
      the env-C2V3 primers used, 10 (58.8%) had discordant subtype or CRF, and 7
      (41.2%) had concordant one based on gag/pol/env-gp41 analysis. Altogether, a high
      proportion (22/57, 38.6%) of the isolates were found to be recombinant strains.
      In addition, an emergence of new forms of HIV-1 strains, such as subtype B/A
      (gag/env), B/CRF01 and B/CRF02, was identified. The epidemiologic pattern of HIV
      1 in eastern Cameroon, relatively low and high prevalence of CRF02 and CRF11,
      respectively, was more closely related to those of CAR and Chad than that of
      other regions of Cameroon, where CRF02 is the most predominant HIV-1 strain.
      These findings strongly suggest that this part of Cameroon is a potential hotspot
      of HIV-1 recombination, with a likelihood of an active generation of new forms of
      HIV-1 variants, though epidemiologic significance of new HIV-1 forms is unknown.

PMID- 15577424
TI  - Magnitude and determinants of first-time and repeat testing among individuals
      with newly diagnosed HIV infection between 2000 and 2001 in Alberta, Canada:
      results from population-based laboratory surveillance.
AB  - The purpose of the study was to determine the magnitude and predictors of first
      time and repeat testing for HIV infection among newly diagnosed cases in Alberta,
      Canada, and to determine the extent of co-infection with hepatitis C (HCV) and
      hepatitis B (HBV). Using the Provincial Laboratory for Public Health (PLPH)
      database, all newly diagnosed HIV cases in Alberta between 2000 and 2001 were
      identified and the testing history for HIV, HCV, and HBV among these cases since
      1992 was reviewed. Significant differences in the characteristics of first-time
      and repeat testers were identified using the chi test, and where appropriate, the
      Fisher exact test. The independent variables examined included age, gender, risk
      factors, area and population of residence, testing agency, and co-infection with
      HCV and HBV. Logistical regression analyses were conducted to further explore
      independent factors associated with first-time vs. repeat testing for HIV
      infection. Of the 398 cases, 278 (69.8%) were newly diagnosed at their first test
      for HIV infection, 73.1% during 2000 and 67.3% during 2001 (P = 0.81). Among
      repeat testers, the mean number of previous negative tests was 3.4 (range = 2-11
      tests). The median interval between the last negative and first positive test was
      648 days (range = 53-2678 days). Repeat testers were 1.9 times more likely to be
      injecting drug users and 1.8 times more likely to reside in Northern Alberta.
      Among those with a laboratory test result in the PLPH database, 53.7% were
      positive for HCV, 47.7 and 64.5% of first-time and repeat testers, respectively;
      and 19.1% were positive for HBV, 22 and 13.6% of first-time and repeat testers,
      respectively. A high proportion of HIV cases newly diagnosed between 2000 and
      2001 in Alberta had no previous testing history for HIV infection. Even among
      repeat testers, HIV testing was sought infrequently. There are significant
      regional differences within Alberta in the characteristics of the HIV epidemic
      and associated test-seeking behaviors. These data reinforce the need to make the
      most of each test-seeking event with proper counseling and other relevant support
      services. Given the high prevalence of co-infection with HCV, these results
      clearly support the need for testing and counseling strategies to take into
      account additional risks associated with HCV infections.

PMID- 15577425
TI  - Micronutrient supplementation increases genital tract shedding of HIV-1 in women:
      results of a randomized trial.
AB  - To test the hypothesis that micronutrient supplementation decreases genital HIV-1
      shedding, a double-blind, randomized, placebo-controlled trial of 6 weeks of
      multivitamin plus selenium supplementation vs. placebo was conducted among 400
      HIV-1-seropositive, nonpregnant, antiretroviral-naive women in Mombasa, Kenya.
      Primary outcome measures included cervical and vaginal shedding of HIV-1-infected
      cells and RNA. Secondary outcomes included plasma viral load and CD4 count.
      Surprisingly, the odds of detection of vaginal HIV-1-infected cells were 2.5-fold
      higher (P = 0.001) and the quantity of HIV-1 RNA in vaginal secretions was 0.37
      log10 copies/swab higher (P = 0.004) among women who received micronutrients in
      comparison to placebo, even after adjustment for potential confounders including
      baseline HIV-1 shedding and CD4 count. The increase in vaginal HIV-1 shedding was
      greatest among women who had normal baseline selenium levels. Micronutrient
      supplementation resulted in higher CD4 (+23 cells/microL, P = 0.03) and CD8 (+74
      cells/microL, P = 0.005) counts compared with placebo but did not alter the
      plasma viral load. In this randomized trial, micronutrients resulted in higher
      levels of genital HIV-1 shedding compared with placebo. The potential benefit of
      micronutrient supplementation in HIV-1-seropositive women should be considered in
      relation to the potential for increased infectivity.

PMID- 15577426
TI  - Current levels of drug resistance among therapy-naive HIV-infected patients have
      significant impact on treatment response.

PMID- 15577427
TI  - A comparison of dyslipidemias associated with either lopinavir/ritonavir- or
      indinavir/ritonavir-based antiretroviral therapy.

PMID- 15577428
TI  - Persistent HIV incidence among injection drug users in San Francisco during the
      1990s: results of five studies.

PMID- 15577429
TI  - Highly active antiretroviral therapy in Turkey: should we follow the
      international guideline or is a modified plan warranted? The jury is still out.

PMID- 15577430
TI  - Communicating with patients.
AB  - The effective clinician realizes that more than accurate factual information is
      necessary for effective communication. The responsibility for this communication
      is the doctor's. Herein is an examination of some of the major areas of
      contention that, if acknowledged by the physician, can lead to better
      communication with the patient.

PMID- 15577431
TI  - Phase II trial of estramustine and etoposide in androgen-sensitive metastatic
      prostate carcinoma.
AB  - BACKGROUND: Early chemohormonal therapy in metastatic prostate cancer may offer
      an advantage by simultaneously targeting androgen-dependent and -independent
      clones. Hence, a phase II trial was conducted to evaluate the efficacy and
      toxicity of estramustine and etoposide in hormone-sensitive metastatic prostate
      cancer. PATIENT AND METHODS: Eligibility consisted of untreated metastatic
      prostate cancer, adequate organ function, and a performance status of 0 to 2 by
      Zubrod criteria. A 21-day schedule of oral estramustine (10 mg/kg/day) and
      etoposide (50 mg/m2/day) was administered every 28 days. Hormonal therapy was
      allowed at the end of the protocol therapy. Toxicity was assessed weekly, PSA
      levels were assessed with each cycle, and objective response was evaluated every
      3 cycles. RESULTS: Twenty-one patients were enrolled (10 white, 11 black) with a
      median age of 59.5 years (range, 42-79 years), a median PSA of 338 ng/mL (range,
      0.9-20,000 ng/mL), and a median Gleason score of 8 points. Ten patients had bone
      only metastases, 11 had measurable disease, of whom 4 had visceral metastases. A
      total of 128 cycles were administered (median, 6 cycles). No dose reductions were
      required. Nineteen patients were able to be evaluated for response. Severe
      toxicities included thromboembolic events and anemia in 2 patients each and
      fatigue in 1 patient. There were no episodes of febrile neutropenia. Response was
      observed in 8 of 11 patients (73%) with measurable disease. Median PSA nadir
      after therapy was 0.45 ng/mL, and undetectable PSA (<0.1 ng/mL) was achieved in 4
      patients. Median time to PSA progression was 16.65 months. At a median follow-up
      of 34 months, 18 patients were alive. The 1-, 2-, and 3-year overall survival
      rates were 90%, 82%, and 72% respectively. Median survival has not yet been
      reached. CONCLUSION: The combination of estramustine and etoposide is well
      tolerated, and has promising activity in newly diagnosed metastatic prostate
      cancer.

PMID- 15577432
TI  - Local-regional radiation therapy after breast reconstruction: what is the
      appropriate target volume? A case-control study of patients treated with electron
      arc radiotherapy and review of the literature.
AB  - The oncologic safety and cosmetic outcome of immediate breast reconstruction in
      breast cancer patients requiring radiation therapy remains ill-defined. Between
      1980 and 1998, 18 patients were treated at the University of Utah Medical Center
      with mastectomy, immediate breast reconstruction, and adjuvant radiation therapy
      delivered via an electron arc technique. A case-control study was performed
      matching reconstructed patients in a 1:2 ratio with patients undergoing
      mastectomy without reconstruction, using number of lymph nodes and tumor size.
      Median follow-up was 61 months for the reconstructed group. Five-year local
      regional control, disease-free survival, and overall survival rates were 87%,
      58%, and 74% respectively in the reconstructed group, versus 88%, 57%, and 67%
      respectively in the matched control group. Cosmesis was good/excellent in 11 of
      13 living patients (85%). Significant capsular contraction occurred in 18% of
      prosthetic reconstruction patients, and revisional surgery was required in 24% of
      prosthetic reconstruction patients. Utilizing the electron arc technique, the
      median radiation dose to the chest wall at the midlevel of the ribs was 20% of
      the prescribed dose, and no patient failed deep to the implant. These results
      suggest that in appropriately selected patients, structures deep to the
      reconstruction are not at high risk for local-regional recurrence, and immediate
      breast reconstruction yields comparable local-regional control, disease-free
      survival, and overall survival rates to nonreconstructed patients, with
      acceptable cosmetic results.

PMID- 15577433
TI  - A Phase II trial of fixed dose rate gemcitabine in patients with advanced biliary
      tree carcinoma.
AB  - Gemcitabine is a commonly used chemotherapy for biliary tree carcinomas,
      achieving response rates of 10% to 60%. Preclinical studies indicate that fixed
      dose rate infusion optimizes accumulation of gemcitabine triphosphate and may
      enhance the clinical activity of gemcitabine. We conducted a phase II study of
      fixed dose rate gemcitabine in 15 chemotherapy-naive patients with advanced
      cholangiocarcinoma and gallbladder carcinoma. Gemcitabine was administered at a
      dose of 1500 mg/m2 over 150 minutes weekly for 3 weeks every 28 days. Fourteen
      patients were evaluable for response. No complete or partial responses were
      observed. Two patients (13%) had stable disease lasting a median of 9 weeks. The
      median time to progression was 9 weeks; median survival was 20 weeks. There was
      considerable grade 3/4 hematologic toxicity, including neutropenia in 49% of
      patients, leukopenia in 40%, anemia in 27%, and thrombocytopenia in 27%. Grade
      3/4 nonhematologic toxicities were minimal. We conclude that fixed dose rate
      gemcitabine results in significant myelosuppression and has minimal activity in
      patients with biliary tree carcinoma.

PMID- 15577434
TI  - Consent documents for oncology trials: does anybody read these things?
AB  - This study was conducted to assess the readability and length of informed consent
      documents used in clinical trials in oncology. One hundred seven consent
      documents from clinical protocols open to accrual at the Emory University Winship
      Cancer Institute were quantitatively analyzed. These included trials sponsored or
      organized internally, by commercial interests, and by various cooperative groups.
      Each form was analyzed using the electronic text version of the consent document
      approved by the Emory University IRB. Readability software was used to determine
      the length of each document and 2 measures of readability: The Flesch Reading
      Ease Score and a grade-level readability estimate using the Gunning Fog Index.
      The mean length +/- SD was 2709 +/- 971 words or 10.8 +/- 3.8 pages. The mean +/-
      SD Flesch Reading Ease Score was 45.48 +/- 5.24. The mean +/- SD grade level
      using the Gunning Fog Index was 11.9 +/- 1.53. None of the consent documents were
      written at or below the 8th-grade reading level; 1.8% were at or below the 9th
      grade level; 10.5% were below the 10th-grade level. Results were similar
      regardless of study sponsor. Consent documents for clinical trials in oncology
      are lengthy and complex to the point that is unlikely that most patients will be
      willing to read them or be able to understand the concepts they discuss. IRBs and
      cooperative group review committees are either unwilling or unable to enforce
      widely accepted readability standards for the consent document. We discuss the
      implications of this situation and suggest ways to improve it.

PMID- 15577435
TI  - Treatment of recurrent Merkel cell carcinoma: an analysis of 46 cases.
AB  - This report describes the course of recurrent Merkel cell carcinoma and defines
      possible treatment strategies for recurrent disease as seen in a long-term
      multisite retrospective analysis. Merkel cell carcinoma is a highly aggressive
      neuroendocrine skin cancer. Surgery and radiation therapy have been demonstrated
      ability to control this disease; however, recurrence is common. Systemic
      chemotherapy has, as yet, no presently defined role in primary treatment, and few
      conclusions can be reached regarding optimal treatment of disease recurrence.
      Forty-six patients were identified over the last 15 years in a retrospective
      analysis of patient records from several hospitals in the San Antonio, TX area.
      Hospital charts as well as outpatient treatment records were reviewed. Almost all
      patients developing recurrent disease did so within the first 2 years after
      primary treatment. Patients presenting distant disease had a median survival of
      12 months, faring worse than those who display local or nodal disease. For
      patients with nodal or local recurrence, the mean survival after combination
      therapy (chemotherapy, radiation +/- surgery) was 36.5 months as compared with
      17.5 months for those treated with a single modality (surgery or radiation or
      chemotherapy). The overall survival rate for the 46 patients with recurrence was
      37%. Multimodality therapy has shown the best results for recurrent Merkel cell
      carcinoma thus far, and should be used if tolerated by the patient. Aggressive
      salvage surgery for local or nodal recurrence is encouraged, because this disease
      has a tendency to become more destructive upon recurrence. Adjuvant radiation
      therapy should also be used, if the patient has not exceeded their dose
      limitations. Disseminated disease, whether primary or recurrent, warrants further
      investigation in terms of optimal treatment.

PMID- 15577436
TI  - Fertility in men after treatment for stage 1 and 2A seminoma.
AB  - The purpose of this article is to assess the long-term fertility and attitudes
      towards fecundity in men after radical inguinal orchiectomy and radiation therapy
      (RT) for seminoma, and also to assess how often sperm cryopreservation is being
      offered to patients with seminoma prior to treatment. A retrospective review was
      conducted at 3 institutions (Wilford Hall Air Force Medical Center, Brooke Army
      Medical Center, and Fitzsimmons Army Medical Center) to identify patients who had
      undergone treatment of stage 1 or 2A seminoma during the period from 1975 to
      1997. Seventy-three of 212 (34%) patients meeting the selection criteria of stage
      1 or 2A seminoma provided information for this analysis. This was thought to be a
      good response rate, given that many of the patients had changed duty stations or
      had separated from the military by the time this study started. We performed a
      review of RT and tumor board records of 73 patients who were treated for
      testicular seminoma at selected treatment facilities from 1975 to 1997. Patients
      completed questionnaires and phone interviews that focused on prior fertility,
      the desire to father (more) children, other fertility-affecting factors
      (varicocele, cryptorchidism, infection, and erectile dysfunction), and incidence
      of physician counseling with regard to cryopreservation. All patients were asked
      to obtain a current semen analysis (SA). Eleven (15%) patients reported that they
      had tried to father children since completion of their RT. Seven of 11 (64%)
      successfully achieved pregnancy within a mean time of 3.5 years since RT (range:
      1 month to 5 years). Of the 4 couples that were not successful, 1 had severe
      female factor infertility problems and a second had organic erectile dysfunction.
      A third had a past surgical history remarkable for vasectomy with subsequent
      vasectomy reversal. Nine patients provided SA. Mean sperm count and motility were
      24.2 Mil/mL (range: 5-81 Mil/mL) and 63.1% (range: 30-90%), respectively (normal
      SA values: count = 20-250 Mil/mL, motility >50%, and volume = 1.5-5.0 mL). No
      patients were azoospermic. Overall mean time interval from radiation therapy was
      7.9 years. Radiation dose and time since RT did not correlate with either SA
      results or conception. Only 16 of 73 (22%) men had been offered pretreatment
      sperm cryopreservation by their counseling physician. It is concluded that (1)
      patients who are treated for early stage seminoma by orchiectomy and RT have
      greater than a 50% chance of regaining normal semen parameters, and all regain at
      least some spermatogenesis; 2) recovery of spermatogenesis is not related to
      therapeutic radiation dose with the use of modern shielding and RT portals; (3)
      the majority of treated patients who desire children can conceive; and (4) sperm
      cryopreservation remains an underutilized option for seminoma patients.

PMID- 15577437
TI  - Biweekly escalated, accelerated hyperfractionated radiotherapy with concomitant
      single-dose mitomycin C results in a high rate of local control in advanced
      laryngeal and hypopharyngeal cancer.
AB  - The purpose of this study is to evaluate the efficacy of a dose-escalated,
      accelerated, and hyperfractionated radiotherapy schedule with a concomitant
      single dose of mitomycin C in the treatment of patients with advanced laryngeal
      or hypopharyngeal cancer. Twenty-one previously untreated patients with advanced
      squamous cell carcinoma (stage III, n = 6; stage IV, n = 15) were treated with a
      biweekly dose-escalated, accelerated, and hyperfractionated schedule up to a
      total dose of 74.4 Gy in 54 fractions over 5 weeks. A single dose of intravenous
      mitomycin C 10 mg/m2 was given on day 30. The median follow-up after treatment of
      surviving patients is 48 months (range, 28 to 61 months). All patients showed
      complete tumor control at the primary site when evaluated 2 months after
      chemoirradiation by laryngomicroscopy or hypopharyngoscopy and radiologic imaging
      (CT, MRI). Two laryngectomies were carried out after given therapy: 1 for
      residual cancer and 1 for suspected residual cancer. After a median follow-up of
      43 months (range, 28 to 61 months), a local control rate of 70% and disease-free
      survival (DFS) rate of 60% were achieved in the laryngeal cancer patients; in
      patients with hypopharyngeal cancer, the corresponding figures were 64% (82%
      after salvage surgery) and 36%. The results are promising and warrant comparison
      with other chemoradiotherapy regimens.

PMID- 15577438
TI  - Final report of a pilot trial of accelerated radiotherapy plus concurrent 96-hour
      infusional paclitaxel for locally advanced head and neck cancer.
AB  - Recent data show that accelerated radiotherapy (XRT) improves local-regional
      control (LRC) over standard-fractionation XRT. Concurrent chemoradiotherapy
      improves LRC and survival over XRT alone. This study assesses the feasibility,
      toxicity, and preliminary efficacy of concurrent 96-hour paclitaxel infusion with
      accelerated XRT. Eligible patients had stage IV squamous cell carcinoma of the
      head and neck, exclusive of nasopharynx cancer. Tumor had to be considered
      technically unresectable after evaluation by our multidisciplinary head/neck
      tumor board. XRT was given continuous course using an accelerated regimen with
      twice a day fractionation for the cone down (70-72 Gy/6 weeks). Chemotherapy
      consisted of 2 cycles of paclitaxel via 96-hour infusion during weeks 1 and 5 of
      XRT. The first 10 patients received doses of 40-120 mg/m2/cycle, and the
      subsequent 13 patients received 100 mg/m2/cycle. Twenty-three patients were
      studied. Median follow-up was 20.4 months (44.4 months for the 10 long-term
      survivors). Most (19/23) patients had reversible grade 3 acute mucositis. Median
      treatment time was 44 days, and all but 1 patient received both cycles of
      paclitaxel at their planned dose. The 3- and 4-year actuarial survival was 37%.
      Three- and 4-year LRC was 50%. Four patients (18%) developed distant metastases.
      Two patients (9%) developed severe esophageal strictures requiring permanent
      gastrostomy/tracheostomy, and 2 patients developed other late grade 3+
      toxicities. Accelerated XRT plus concurrent 96-hour infusional paclitaxel as
      given in this study has intense but acceptable toxicity and is feasible. LRC and
      survival compare favorably with other aggressive regimens for this poor-prognosis
      population. Further study of accelerated XRT with concurrent chemotherapy is
      indicated.

PMID- 15577439
TI  - Preliminary results of a phase II study of weekly paclitaxel (PTX) and
      carboplatin (CBDCA) administered concurrently with thoracic radiation therapy
      (TRT) followed by consolidation chemotherapy with PTX/CBDCA for stage III
      unresectable non-small-cell lung cancer (NSCLC).
AB  - Concurrent chemoradiotherapy plays an important role in the treatment of
      unresectable NSCLC. This phase II study was conducted to evaluate the efficacy
      and toxicity of paclitaxel (PTX) and carboplatin (CBDCA) at a recommended dose,
      based on other previous phase I studies. Twenty-two unresectable stage III NSCLC
      patients participated in this trial. Of those 22 patients, 19 were evaluable,
      with a median age of 57 (with ages ranging between 42 and 74), in stages
      IIIA/IIIB: 6/13. Every patient displayed adequate organ functions. Treatment
      consisted of a 1-hour i.v. infusion of 50 mg/m2 of PTX followed by a half-hour
      infusion of CBDCA AUC 2 administered weekly concurrently with radiation
      treatment, every first day of those weeks in which the patient underwent
      radiotherapy. Concurrent thoracic radiation therapy was performed in daily doses
      of 2 Gy to a total dose of 66 Gy over a period of 6.5 weeks. After completion of
      chemoradiotherapy, consolidation chemotherapy was administered via a 3-hour i.v.
      infusion of 175 mg/2 PTX on days 1 and 22, in combination with a 1-hour i.v.
      infusion of CBDCA AUC 6 on days 1 and 22, q 4 weeks for 4 cycles. The overall
      response rate was 78.9% (95% CI: 62-87.7) with 5 CR (26.3%), 10 PR (52.6%), 2 SD
      (15.8%), and 1 PD (5.3%). The median survival rate of the patients was 13.9
      months, and the 1-year survival rate was 65.1%. Toxicity was moderate: grade 2
      neutropenia was seen in 8, and grade 3 neutropenia in 5 patients. Grade 2
      thrombocytopenia was seen in 3 patients, and grade 3 thrombocytopenia was not
      observed. Nonhematologic toxicities were moderate: esophagitis was the most
      common, and significant toxicity was noted in this study (89.4%). Grade 1
      asthenia/fatigue was observed in 5, and grade 2 asthenia/fatigue in 3 patients;
      furthermore, grade 1 peripheral neuropathy was seen in 4 of the cases and grade 2
      peripheral neuropathy in 3 of the cases. Concurrent chemoradiotherapy with weekly
      PTX/CBDCA, followed by consolidation chemotherapy with the same regimen in
      patients with stage III unresectable NSCLC is feasible and well tolerated.

PMID- 15577440
TI  - Permanent interstitial brachytherapy for clinically organ-confined high-grade
      prostate cancer with a pretreatment PSA < 20 ng/mL.
AB  - The objective of this study was to determine the effect of biopsy Gleason score 8
      and 9 histology on biochemical outcome following a permanent prostate
      brachytherapy approach that includes multiple periprostatic seeds and
      supplemental external beam radiation. Forty-six consecutive T1c-T2b (1997 AJCC)
      patients with Gleason score 8 and 9 prostate cancer who were either hormone naive
      (33 patients) or received cytoreductive (< or =6 months) hormonal therapy (13
      patients) underwent brachytherapy from June 1995 to November 2000. The median
      patient age was 69.7 years, with a median pretreatment prostate-specific antigen
      (PSA) of 7.7 ng/mL. The median follow-up was 58 months (range 27-93 months).
      Forty-five of the patients were implanted with Pd-103 and 44 received
      supplemental external beam radiation therapy (45 Gy). Biochemical success was
      defined by either a PSA < or = 0.4 ng/mL after a nadir or by the ASTRO consensus
      definition. The actuarial 7-year biochemical disease-free survival was 84.8%
      using either a PSA < or = 0.4 ng/mL or the ASTRO consensus definition. The median
      postimplant PSA was less than 0.1 ng/mL for both the hormone naive and hormonally
      manipulated patients. The utilization of hormonal therapy for 6 months or less
      duration resulted in a statistically nonsignificant improvement in biochemical
      outcome (92.3% versus 81.8%, P = 0.393). When stratified by pretreatment PSA,
      87.9% of patients with a pretreatment PSA < or = 10 ng/mL and 76.9% with a
      pretreatment PSA > 10 ng/mL (P = 0.377) remained biochemically free of disease.
      In multivariate analysis, none of the clinical, treatment, or dosimetric
      parameters predicted for outcome. Following a permanent prostate brachytherapy
      approach that used multiple periprostatic seeds, the majority of patients with
      clinically organ-confined Gleason score 8 and 9 prostate cancer remain
      biochemically free of disease with identical outcomes for both biochemical
      definitions of success.

PMID- 15577441
TI  - Interfraction interval in patients with stage III non-small-cell lung cancer
      treated with hyperfractionated radiation therapy with or without concurrent
      chemotherapy: final results in 536 patients.
AB  - We investigated the influence of interfraction interval (IFI) on treatment
      outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated
      with hyperfractionated radiation therapy (Hfx RT) with or without concurrent
      chemotherapy (CHT). During 3 randomized phase III and 1 phase II study, a total
      of 536 patients were treated with Hfx RT alone or with concurrent
      carboplatin/etoposide. Two hundred eighty-five patients were treated with IFI of
      4.5-5.0 hours, while 251 patients were treated with IFI of 5.5-6.0 hours.
      "Shorter" (4.5-5.0 hours) IFI led to better overall survival (OS) (P = 0.0000)
      and local recurrence-free survival (LRFS) (P = 0.0000). Multivariate analyses
      showed IFI to be an independent prognosticator of both OS and LRFS. These results
      were confirmed when we separated all patients (n = 536) into those treated with
      Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409). Various
      RT-related high-grade acute toxicity was not different between the 2 IFI, but
      patients treated with shorter IFI had a significantly higher incidence of
      hematological toxicity (P = 0.002). None of the late high-grade toxicities were
      different between the 2 interfraction intervals. Using regression analysis, it
      was shown that IFI was not a significant predictor of any of acute or late high
      grade (> or =3) toxicity. IFI is an important prognosticator of OS and LRFS in
      patients with stage III NSCLC treated with Hfx RT with or without concurrent
      carboplatin/etoposide. IFI led to higher incidence only of hematological
      toxicity, but was not predictive of any acute or late high-grade (> or =3)
      toxicity. A carefully designed randomized trial seems necessary to give better
      insight into the issue of optimal IFI in this disease.

PMID- 15577442
TI  - Preliminary reliability and validity testing of a new Skin Toxicity Assessment
      Tool (STAT) in breast cancer patients undergoing radiotherapy.
AB  - Clear consensus on the clinical evaluation of acute skin toxicity among cancer
      patients undergoing radical radiotherapy (RT) is currently lacking. This study
      investigates the reliability and validity of a new Skin Toxicity Assessment Tool
      (STAT) to evaluate the objective and subjective manifestations of RT-induced
      acute skin effects. The STAT was designed by a multidisciplinary team involved in
      the management of radiation skin reactions. The tool has 3 components: patient
      and treatment parameters, observer scoring, and patient-reported symptoms, and
      was piloted in a cohort of 27 breast cancer patients by pairs of independent
      blinded observers. Each patient was assessed weekly during RT and 2 weeks after
      therapy completion. Validity and reliability testing of the STAT was performed.
      Information on the tool's ease of use was obtained by recording the time
      necessary to complete the assessment at each visit and by a survey among the
      tool's users. All subjects developed some degree of skin reaction during breast
      RT. The level of agreement between observers in eliciting subjective complaints
      ranged from 72% to 92% (95% CI = 63-96%; kappa = 0.33-0.68). The interobserver
      agreement in scoring skin reactions ranged from 65.0 to 97.5% (kappa = 0.46
      0.81). Objective and subjective toxicity scores were significantly correlated (P
      < 0.05). The STAT was easy to use and required on average a few minutes to
      complete at each visit. The STAT is an easy-to-use, standardized instrument to
      evaluate acute skin reaction and may be applied to clinical care and research in
      patients undergoing radiotherapy.

PMID- 15577443
TI  - Brain metastases in renal cell cancer: diagnostic and therapeutic aspects.
AB  - A 67-year-old patient with metastatic renal cell cancer was treated with
      fractionated stereotactic radiotherapy to a hemorrhagic pons metastasis. He then
      developed multiple cystic brain lesions, suggestive of diffuse metastatic spread.
      However, further work-up revealed abscesses from bronchopneumonia. Diagnostic and
      therapeutic aspects as well as potential pitfalls in the management of patients
      with brain metastases are discussed.

PMID- 15577444
TI  - Synchronous primary bilateral breast lymphoma.

PMID- 15577445
TI  - Unsuspected testicular metastases from Merkel cell carcinoma: a case report with
      therapeutic implications.

PMID- 15577446
TI  - Solitary dural extramedullary plasmacytoma with inv(9)(p13q21).
AB  - The authors report the case of a 24-year-old man who presented with a solitary
      dural extramedullary plasmacytoma (EMP) with inv(9)(p13q21). Chromosome 9
      aberrations may be associated with the pathogenesis. This is the first reported
      case of solitary dural EMP associated with inv(9)(p13q21).

PMID- 15577447
TI  - Primary presentation of glioblastoma multiforme with leptomeningeal metastasis in
      the absence of previous craniotomy: a case report.
AB  - Glioblastoma multiforme is a highly malignant glioma with a well-known tendency
      for intracranial spread but rarely for extracranial spread. We report a case of
      an adult woman who presented with symptoms of leptomeningeal metastasis from an
      intracranial glioblastoma multiforme located adjacent to the lateral ventricle.
      There have been very few cases of glioblastoma multiforme presenting with
      leptomeningeal metastasis in the absence of previous therapeutic intervention.

PMID- 15577448
TI  - Endoscopic stenting of the common bile duct allows successful treatment of a
      breast cancer patient with excessive liver metastases.
AB  - The treatment of a jaundiced patient with hyperbilirubinaemia due to breast
      cancer liver metastases is still a challenging problem. The associated hepatic
      dysfunction often represents a limiting factor for delivering standard dose
      chemotherapy. We report on the successful treatment of a jaundiced patient with
      excessive, recurrent liver metastases from breast cancer, using a combined
      chemotherapy of mitomycin and 5-fluorouracil after endoscopic stenting of the
      common bile duct.

PMID- 15577449
TI  - Adenocarcinoma arising from ectopic gastric mucosa in the cervical esophagus.
AB  - Ectopic (heterotopic) gastric mucosa (EGM) of the upper esophagus, referred as
      inlet patch, is an asymptomatic benign lesion that is often detected during
      endoscopic examination. Although it is considered a source of adenocarcinoma in
      the upper esophagus, only 17 cases of adenocarcinoma have been reported
      previously. We report a rare case of adenocarcinoma arising in EGM of the
      cervical esophagus.

PMID- 15577450
TI  - Definitive, high-dose-per-fraction, conformal, stereotactic external radiation
      for renal cell carcinoma.
AB  - INTRODUCTION: Localized renal cell carcinoma is conventionally treated
      surgically. Preoperative and adjuvant external radiation have not improved
      survival. However, renal cell cancer brain metastases, although radioresistant to
      conventional external radiation, have been responsive to radiosurgery. The
      following report was compiled with information from our experience using high
      dose-per-fraction, conformal radiation delivered to patients who refused
      definitive surgery. MATERIALS AND METHODS: Nine patients with nonmetastatic renal
      cell carcinomas were identified, 2 of which had bilateral renal cell cancers.
      Patients were treated definitively with 40 Gy in 5 fractions using conformal
      external radiation. RESULTS: With a median follow up of 26.7 months, 4 of the 9
      patients are alive. The survivors have a minimum follow up of 48 months. At
      presentation, all 4 of the survivors had tumors < or =3.4 cm in largest
      dimension, had clinically negative nodes, and presented no clinical evidence of
      penetration of Gerota fascia or renal vein extension. CONCLUSION: High-dose-per
      fraction, conformal external radiation may have a curative role for small, node
      negative, organ-confined renal cell carcinomas.

PMID- 15577451
TI  - Effects of a selective 5-HT1B receptor agonist and antagonists in animal models
      of anxiety and depression.
AB  - The purpose of the present study was to investigate the effects of the selective
      5-HT1B receptor agonist CP 94253, the selective 5-HT1B receptor antagonist SB
      216641, and the 5-HT1B/1D receptor antagonist GR 127935 in behavioral tests
      commonly used to predict anxiolytic- and antidepressant-like activity. Diazepam
      and imipramine were used as reference drugs. In the Vogel conflict drinking test,
      CP 94253 (1.25-5 mg/kg), SB 216641 (2.5-5 mg/kg) and GR 127935 (5-10 mg/kg)
      showed anxiolytic-like effects comparable to that of diazepam (2.5-5 mg/kg). In
      the elevated plus-maze test, antianxiety-like activity of all the compounds
      tested was also observed: the effects of CP 94253 (2.5 mg/kg) and SB 216641 (5
      mg/kg) were similar to that of diazepam (5 mg/kg), while GR 127935 (up to 40
      mg/kg) was less active. In the four-plate test, the compounds tested (5-10 mg/kg)
      produced anxiolytic-like effects which were weaker than that of diazepam (2.5-5
      mg/kg). In the forced swimming test, CP 94253 (5-10 mg/kg), like imipramine (30
      mg/kg), showed anti-immobility action, whereas SB 216641 (2.5-10 mg/kg) and GR
      127935 (20-40 mg/kg) did not affect the immobility time in mice. The results
      indicate that the selective agonist (CP 94253) and antagonists (SB 216641 and GR
      127935) of 5-HT1B receptors produce effects that are characteristic of
      anxiolytics, in the preclinical models used; however, CP 94253 also behaves like
      an antidepressant drug.

PMID- 15577452
TI  - Differential effects of midazolam and pentylenetetrazole on behavioral repetition
      and variation.
AB  - The present study investigated the effects of midazolam and pentylenetetrazole
      upon repeating and varying sequences of responses. Rats were exposed to a
      multiple schedule with two components. Under the VARY component, water was
      provided if the current sequence of four responses differed from each of the five
      previous ones; under the REPEAT component, water delivery was contingent upon a
      particular four-response sequence. Each component was signaled by specific
      exteroceptive stimuli. Overall, sequence variability was affected by midazolam,
      and to a lesser degree, by pentylenetetrazole. With the REPEAT contingency, drug
      administration increased behavior variation, thus reducing accuracy; with the
      VARY contingency, behavior variation and accuracy were not altered. These results
      were explained on the basis of the disruptive effects of both drugs upon the
      discriminative control exerted by previous responses within a sequence and by
      exteroceptive stimuli.

PMID- 15577453
TI  - Role of anxiety levels in memory performance of spontaneously hypertensive rats.
AB  - Spontaneously hypertensive rats (SHR) show behavioural differences when compared
      to their strain-matched controls. These differences include decreased anxiety
      like behaviour in SHR, while both improved performance and behavioural deficits
      have been reported in learning/memory studies. Considering that alterations in
      anxiety levels during the training session can modify retention performance in
      animal models of memory, the aim of the present study was to investigate the role
      of anxiety levels in the performance of SHR rats in the plus-maze discriminative
      avoidance task (PM-DAT), in which memory and anxiety are evaluated
      simultaneously. Adult (5-month-old) and young (45-day-old) SHR and normotensive
      Wistar rats (NWR) were treated with chlordiazepoxide (CDZ) or saline. Thirty
      minutes later, rats were submitted to the PM-DAT training session. After 24 h,
      the test session was performed. The results showed that: (1) adult SHR showed
      lower anxiety levels compared to adult NWR; (2) adult SHR and NWR, as well as
      young NWR, showed significant retention of the task, while young SHR showed
      impaired performance; (3) 5.0 mg/kg CDZ decreased anxiety levels in adult NWR and
      young and adult SHR; (4) 5.0 mg/kg CDZ impaired retention in adult SHR and NWR
      and increased retention in young SHR. Our data suggest an important role of
      anxiety levels in the performance of SHR in a plus-maze discriminative avoidance
      task.

PMID- 15577454
TI  - Discriminative stimulus effects of ethanol in rats using a three-choice ethanol
      midazolam-water discrimination.
AB  - Three-choice discrimination procedures are used to characterize how similar the
      discriminative stimulus effects of two drugs are in relation to each other. This
      procedure has suggested similarities between ethanol and ligands that positively
      modulate the gamma-aminobutyric acid type A (GABAA) receptor complex. As an
      extension to these studies, male Long-Evans rats were trained to discriminate
      midazolam (3.0 mg/kg, i.p.) from ethanol (1.0 g/kg, i.g.) from water (2.3 ml,
      i.g.) in a three-lever, food reinforced task. Substitution tests were conducted
      following administration of GABAA-positive modulators, noncompetitive N-methyl-D
      aspartate (NMDA) antagonists, 5-HT1B agonists and isopropanol. Among the GABAA
      positive modulators, diazepam was the only drug that completely substituted for
      midazolam; both pentobarbital and the neurosteroid allopregnanolone showed
      partial midazolam substitution. The NMDA antagonist dizocilpine substituted for
      ethanol, while phencyclidine showed no substitution for either ethanol or
      midazolam. The serotonin agonists tested also showed no substitution for either
      ethanol or midazolam. Isopropanol was the only other drug that completely
      substituted for ethanol. These data extend previous findings from an ethanol
      pentobarbital-water discrimination and further define training conditions that
      result in a conditional basis for the ethanol discrimination where only those
      drugs with pharmacological heterogeneous effects similar to ethanol produce a
      full ethanol-like effect.

PMID- 15577455
TI  - Tolerance to the discriminative stimulus effects of ethanol following chronic
      inhalation exposure to ethanol in C57BL/6J mice.
AB  - A significant consequence of chronic ethanol (EtOH) exposure is the development
      of tolerance. The present study was designed to investigate tolerance to the
      discriminative stimulus properties of EtOH following chronic EtOH exposure. Adult
      male C57BL/6J mice were trained to discriminate EtOH (1.00 g/kg; i.p.) from
      saline, using a food-reinforced two-lever operant task. Following acquisition and
      establishment of criterion discrimination performance, a series of generalization
      tests were conducted to generate a baseline EtOH dose-response curve with a
      calculated ED50 dose of 0.42 g/kg. Mice were then placed into control (air) or
      EtOH inhalation chambers for 64 h. In Experiment 1, discriminative stimulus
      generalization tests with the EtOH ED50 dose conducted 24 h following chronic
      EtOH (or air) exposure did not yield significantly different EtOH responding,
      although a trend towards reduced sensitivity to the EtOH cue (tolerance) was
      evident. In Experiment 2, a cumulative dosing procedure (ED50=0.37 g/kg) was
      employed, yielding a baseline EtOH dose-response function with a calculated ED50
      dose of 0.37 g/kg. At 24 h following chronic EtOH exposure, re-determination of
      the EtOH dose-response curve revealed a significant shift to the right, with more
      than a twofold increase in the ED50 value (ED50=1.09 g/kg) compared to the
      control air exposure condition (ED50=0.49 g/kg). This apparent tolerance to the
      EtOH cue dissipated in chronic EtOH-exposed mice tested 48 h following the
      inhalation treatment (ED50=0.51 g/kg). These results demonstrate tolerance to the
      discriminative stimulus effects of EtOH in C57BL/6J mice following chronic EtOH
      exposure in inhalation chambers.

PMID- 15577456
TI  - Fencamfamine-induced changes in the parameters of the matching law and the effect
      of previous exposure to the drug.
AB  - The purpose of this study was to assess the effects of the psychomotor stimulant
      fencamfamine (FCF) on the operant response rate and on the parameters k and R(e)
      of Herrnstein's hyperbola. In the first experiment, rats were trained on a
      multiple variable interval (VI) schedule. Each rat was then given two i.p.
      injections of a randomly assigned FCF dose (0.0, 0.88, 1.75 and 3.5 mg/kg) at 48
      h intervals. The overall response rate, the individual VI response rate, and the
      k and R(e) parameters of the hyperbola equation were calculated. In the second
      experiment, two groups of animals were trained drug-free on the same schedule.
      Afterwards, the animals in one group received six i.p. injections of 1.75 mg/kg
      FCF at 48 h intervals while subjects in the other group received vehicle
      injections, 15 min before each experimental session. Seven days after the last
      injection, a challenge dose (0.88 mg/kg) of FCF was administered and performance
      was measured. FCF increased overall response rate and decreased R(e) without
      changing k. Previous exposure to FCF did not induce sensitization of these
      measures. These results indicate that FCF has similar effects on k and R(e) as
      those produced by other indirect dopaminergic agents, and supports previous
      findings suggesting FCF as a potential drug of abuse.

PMID- 15577457
TI  - Sodium benzoate attenuates iminodipropionitrile-induced behavioral syndrome in
      rats.
AB  - This study reports the effects of the antioxidant sodium benzoate (SB) on
      iminodipropionitrile (IDPN)-induced excitation with choreiform and circling (ECC)
      syndrome in adult female Wistar rats. Rats in four different groups (n=8)
      received i.p. injections of SB (0, 50, 100 and 200 mg/kg) daily for 10 days. IDPN
      (100 mg/kg, i.p.) was administered daily 30 min before SB for the first 8 days.
      Two additional groups served as control (vehicle) and SB alone (200 mg/kg)
      groups. The animals were observed daily for neurobehavioral abnormalities,
      including dyskinetic head movements, circling, tail hanging, righting reflex and
      contact inhibition of the righting reflex, characterized as the ECC syndrome. In
      the IDPN-alone treated group, the onset of ECC syndrome occurred on day 9 (2 out
      of 8 rats), whereas none of the animals treated with IDPN plus SB (100 or 200
      mg/kg) showed any signs of ECC syndrome on that day. All the animals in the IDPN
      alone group developed severe dyskinesia on day 11. Treatment of rats with SB
      significantly and dose-dependently attenuated IDPN-induced behavioral deficits.

PMID- 15577458
TI  - Editorial comment.

PMID- 15577459
TI  - Posterior exposure of the hip joint.

PMID- 15577460
TI  - The Otto Aufranc Award. Highly cross-linked polyethylene in total hip
      arthroplasty: randomized evaluation of penetration rate in cemented and
      uncemented sockets using radiostereometric analysis.
AB  - The annual wear rate in polyethylene articulations should be 0.1 mm or less to
      avoid future osteolysis. Highly cross-linked polyethylene shows an 80 to 90% wear
      reduction in hip simulator testing, but the clinical documentation of this new
      polyethylene is still inadequate. We evaluated the highly cross-linked
      polyethylene in two prospective randomized clinical studies. Thirty-two patients
      (12 men, 20 women; 64 hips) with a median age of 48 years (range, 29-70 years)
      with bilateral primary or secondary arthrosis of the hip had hybrid total hip
      arthroplasty with liners made of highly cross-linked polyethylene on one side and
      conventional polyethylene on the other. Twenty-seven patients in this study have
      passed 2 years followup. A further group, comprised of 60 patients (61 hips) with
      a median age of 55 years (range, 35-70 years), was randomized to receive either
      highly cross-linked polyethylene or conventional cemented all-polyethylene of the
      same design. Forty-nine of these 60 patients have been observed for 3 years. In
      both studies all patients received Spectron stems with 28-mm Co-Cr heads.
      Radiostereometric examinations with the patient supine or standing were done at
      regular intervals. Wear was measured in the supine position from the first
      postoperative week, whereas standing examinations were initiated 3 months after
      the operation. The penetration rate almost was identical in the study and control
      groups at 6 months after the operation. Thereafter, the penetration rate leveled
      out in the two groups with highly cross-linked polyethylene. At 2 years the
      highly cross-linked polyethylene liner showed 62% lower proximal penetration and
      31% lower total (three-dimensional) penetration when the patients were examined
      in supine position. The highly crosslinked all-polyethylene cemented cups showed
      lower proximal penetration in both positions. The better wear performance of
      highly cross-linked polyethylene could increase the implant longevity. Longer
      followup is needed to evaluate if this new material is associated with less
      occurrence of osteolysis.

PMID- 15577461
TI  - The John Charnley Award Paper. The role of joint fluid in the tribology of total
      joint arthroplasty.
AB  - The effect of joint fluid on the tribology (ie, lubrication, friction, and wear)
      of total hip arthroplasty has not yet been investigated adequately. In the
      current study, a friction assay was used to assess four hypotheses relating to
      the effect of human joint fluid and its principal components on the articulation
      of metal-on-polyethylene. First, joint fluid was found to produce a widely
      varying amount of friction between cobalt-chromium and polyethylene; this range
      exceeded the range produced when the articulation was lubricated by water or
      bovine serum. Second, it was shown that hyaluronic acid, phospholipid, albumin,
      and gamma-globulin were not acting as boundary lubricants, but that one or more
      other proteins (as yet unidentified) were responsible for reducing friction in
      this couple. Third, lower friction was found when oxidized zirconium alloy
      replaced cobalt-chromium as a bearing surface on polyethylene. Finally, a pilot
      study suggested that lubricin, which contributes to cartilage-on-cartilage
      lubrication, is not a protein responsible for the tribological variabiation found
      among joint fluid samples. The current study showed that joint fluid is a patient
      factor that influences the tribology of metal-on-polyethylene arthroplasty.

PMID- 15577462
TI  - Frank Stinchfield Award. Titanium surface with biologic activity against
      infection.
AB  - Despite immense improvements, periprosthetic infection continues to compromise
      the result of otherwise successful joint arthroplasty. There are various
      limitations in the treatment of periprosthetic infection, the most important of
      which is the inability to deliver antibiotics to the local tissue without the
      need for intravenous administration. We have developed a novel route to
      covalently tether vancomycin to a metal (titanium) surface, which showed
      effective bactericidal activity because of a vancomycin coupling. The chemistry
      of tethering does not affect the biological activity of the biofactors that are
      attached to the metal surface. This technology holds great promise for the
      manufacturing of "smart" implants that can be self protective against
      periprosthetic infection, or can be used for the treatment of periprosthetic
      infections when they occur.

PMID- 15577463
TI  - Conquest of a worldwide human disease: particle-induced periprosthetic
      osteolysis.
AB  - It is rare in the long history of human disease to encounter a completely unique
      disease. In the 21st century, when it does occur, the disease commonly is man
      made, as is true for periprosthetic osteolysis. However, it also is rare to
      unravel the mysteries of a biologic process as complex as periprosthetic
      osteolysis in slightly longer than one generation and even less common to create
      the means for the worldwide prevention of an entire disease. Such is the story of
      periprosthetic osteolysis. The adventure from the iatrogenic creation of the
      disease to the identification of its pathology, to the understanding of its
      molecular biology and, subsequently, to its prevention, during a period of four
      decades, is a fascinating story of medical detective work.

PMID- 15577464
TI  - Total hip arthroplasty: optimal treatment for displaced femoral neck fractures in
      elderly patients.
AB  - Although internal fixation is recommended for most nondisplaced fractures of the
      femoral neck, the optimal treatment for displaced fractures of the femoral neck
      is controversial. Options for operative treatment of displaced fractures of the
      femoral neck include: reduction and internal fixation; unipolar hemiarthroplasty;
      bipolar hemiarthroplasty; and total hip arthroplasty. One hundred eighty-six
      displaced fractures of the femoral neck in elderly patients were treated
      surgically with internal fixation (in 120 patients), hemiarthroplasty (in 43
      patients), and total hip arthroplasty (in 23 patients). One hundred twenty
      patients with displaced fractures treated with internal fixation were compared
      with 66 patients with displaced fractures treated with arthroplasty. Criteria for
      comparison were reoperation, mortality, hospital discharge disposition,
      functional outcome, living status, and cost effectiveness. There was no
      difference in rates of reoperation or mortality, but arthroplasty produced a
      longer interval to reoperation or death. Arthroplasty was associated with more
      independent living, and arthroplasty was more cost-effective than internal
      fixation. Total hip arthroplasty was the best treatment for displaced fractures
      of the femoral neck in elderly patients in this series.

PMID- 15577465
TI  - The role of total hip replacement in intertrochanteric fractures of the femur.
AB  - Total hip replacement is rarely used in the treatment of acute intertrochanteric
      fractures of the femur. Pathologic fractures with involvement of the femoral head
      and/or periacetabular pelvis may represent one such indication; rheumatoid
      arthritis with or without radiographic involvement of the joint space or end
      stage osteoarthritis with substantial hip symptoms before fracture may represent
      other indications. Total hip replacement is mainly reserved for the treatment of
      complications such as nonunion or avascular necrosis of the femoral head.

PMID- 15577466
TI  - The pros and cons of polyethylene sterilization with gamma irradiation.
AB  - This retrospective study evaluated the implant, patient and surgical factors
      associated with polyethylene wear for one type of porous-coated hemispheric total
      hip arthroplasty cup. Radiographic wear measurements among 567 Duraloc cups (512
      patients) revealed that liners sterilized by gamma-irradiation wore 0.085 mm/year
      less than those that were sterilized by gas-plasma, a noncross-linking chemical
      surface treatment. The substantially decreased wear rate associated with gamma
      irradiation was attributed to sterilization-induced polyethylene cross-linking.
      Shelf-aging adversely affected liners that were gamma irradiated in air. On
      average, highly crystalline Hylamer liners showed a 0.064 mm/year increase in
      wear rates for each year of shelf storage after terminal sterilization with gamma
      irradiation in air. Among conventional Enduron liners, the effect of shelf aging
      after gamma-irradiation in air was more modest, increasing wear rates by 0.014
      mm/year for each year of shelf storage. Because Hylamer's wear performance
      degraded at about five times the rate of Enduron's, the improved wear resistance
      associated with gamma-irradiation in air would be lost after 1.3 years of shelf
      aging for Hylamer compared with 6.1 years for Enduron. For every additional year
      of age at the time of surgery, the wear rate decreased by 0.003 mm/year.
      Increased body mass index, a preoperative diagnosis of inflammatory arthritis,
      and a ceramic femoral head also were associated with decreased wear rates.

PMID- 15577467
TI  - Highly cross-linked, electron-beam-irradiated, melted polyethylene: some pros.
AB  - Extensive new evidence generated within the past the year provides strong support
      for the use of electron-beam highly cross-linked, subsequently melted ultra-high
      molecular weight polyethylene in total hip replacement arthroplasty. In terms of
      wear reduction, three studies involving three different demographic groups and
      two different measurement techniques have found that the femoral head penetration
      with this type of polyethylene after bedding in has finished taking place is less
      than 10 micra per year. This wear rate is similar to the wear rate of metal-on
      metal and ceramic-on-ceramic articulations. Retrieval specimens up to 3 years
      after insertion confirmed the minimal wear by exhibiting persisting machine marks
      throughout the inside diameter of the liner. Extensive studies show no evidence
      of oxidation, confirming the absence of residual free radicals. No evidence of
      fatigue failure exists except three known cases out of 150,000, in which
      malposition of the acetabular component produced abnormally high contact stresses
      on unsupported polyethylene. The in vivo wear, oxidation resistance, and
      mechanical properties of this alternative bearing material are excellent, with in
      vivo durations now exceeding five years. The other major advantages over hard-on
      hard bearings including familiarity, adaptability, forgiveness, and cost seem to
      be compelling.

PMID- 15577468
TI  - Fatigue crack propagation resistance of highly crosslinked polyethylene.
AB  - A higher degree of cross-linking has been shown to improve wear properties of
      ultra-high molecular weight polyethylene in laboratory studies. However, cross
      linking can also affect the mechanical properties of ultra-high molecular weight
      polyethylene. Fatigue crack propagation resistance was determined for electron
      beam cross-linked ultra-high molecular weight polyethylene and compared with
      gamma irradiation cross-linked and noncross-linked polyethylene fatigue
      specimens. Crosslinking was done with different dosages of irradiation followed
      by melting. For one irradiation dose (50 kGy) extrusion and molding processes
      were compared. A fracture mechanics approach was used to determine how the degree
      of cross-linking affects resistance to crack propagation in ultra-high molecular
      weight polyethylene. Fatigue crack propagation resistance was reduced in
      proportion to the irradiation dose. The type of irradiation (gamma or electron
      beam) or manufacturing method (extrusion or molding) did not affect fatigue crack
      propagation resistance. The reduced fatigue strength of highly cross-linked ultra
      high molecular weight polyethylene could lead to mechanical failure in conditions
      that are associated with cyclic local tensile stresses.

PMID- 15577469
TI  - Concerns about ceramics in THA.
AB  - Currently available ceramic materials are superior to those used originally in
      total hip arthroplasty, which should translate into a much lower complication
      rate than what has been reported previously. In spite of this, a number of
      concerns remain. The ceramic-on-ceramic articulation is not immune to wear and
      surface damage. Conditions associated with ceramic wear include vertical cup
      position, femoral neck impingement, and femoral head separation. A unique pattern
      of stripe wear has been described as something that results from microseparation
      during gait. Catastrophic failure, although rare, continues to be a concern, and
      not all fractures can be predicted by proof testing. Revisions needed because of
      ceramic fractures can be extensive, and the results of the revision procedures
      can be compromised by the presence of highly abrasive particulate debris that is
      retained. Other concerns include the generation of debris from modular
      interfaces, neck damage and debris generation from impingement of some designs,
      inability to use a ceramic head a second time on a metal trunnion, and the
      dramatic loss of head and liner options intraoperatively. Although ceramics show
      great promise as a lower wear articulation, manufacturing and design
      modifications and improvements will continue in an attempt to address the
      substantial concerns that persist.

PMID- 15577470
TI  - The argument for the use of Metasul as an articulation surface in total hip
      replacement.
AB  - Metasul metal-on-metal articulations have been used for 15 years in approximately
      300,000 total hip replacements. We have used Metasul articulations in three
      clinical studies and have shown clinical success as measured by Harris hip scores
      and patient self-assessment; we also have had the usual mechanical complications.
      The only complications have been mechanical, including two cup loosenings and 24
      dislocations in a total of 582 patients (619 hips; 3.8%) who had Metasul
      articulations and were included in these studies. In the randomized study, the
      group who had Metasul articulations had no clinical results or complications
      different from the control ceramic-on-polyethylene group. Authors of retrieval
      results in the literature report low annual linear wear rates and no consequences
      of elevated Co ion levels. Currently, the scientific evidence of the results of
      using the Metasul articulation would recommend its continued use in any patient
      who does not have compromised renal function.

PMID- 15577471
TI  - Metal-on-metal total hip arthroplasty: the concerns.
AB  - The metal-on-metal bearing couple is having a resurgence in clinical applications
      seen in total hip and hip resurfacing technologies. The most noteworthy advantage
      of a metal-on-metal implant is the improved wear characteristics seen in vitro on
      wear simulators and in vivo with retrieved implants. All bearings have
      disadvantages, and a metal-on-metal bearing is no exception. Concerns exist
      regarding the generation of metal ions seen in the blood and urine of patients
      with metal-on-metal implants. These elevated metal ions have theoretical,
      although not proven, risks related to carcinogenic and biologic concerns.
      Additionally, concerns exist regarding hypersensitivity, increased incidence of
      instability and increased costs. Specific patient selection issues arise with
      metal-on-metal implants. The current generation of implants has only early and
      mid-term results available, with no long-term series yet published. Therefore,
      although a metal-on-metal bearing may be considered a viable alternative to
      either polyethylene or ceramic implants, outstanding and unresolved issues
      continue to exist with this bearing, as they do with the alternatives.

PMID- 15577472
TI  - Results of reoperation for hip dislocation: the big picture.
AB  - Hip instability remains a costly complication of primary (3%) and revision (10%)
      procedures. In those with well-oriented components, instability may be
      anticipated in about 70% from advancement of the trochanter. Articular
      reorientation readily is affected by the use of modular cups with elevated rims.
      This has proven to be an effective strategy both to lessen the likelihood of an
      initial dislocation after both primary and revision procedures. It has also
      proven to be an effective strategy to treat the unstable implant, especially if
      cup orientation has been defined as the primary problem. Larger head sizes in the
      range of low-friction arthroplasty, such as 32 mm, are not any more stable than
      22-mm diameter implants. Anatomic-sized heads as used in bipolar devices are
      effective in treating established instability in up to 90% of instances. The most
      popular current option is that of the constrained head/cup articulation. Good
      short-term results have revealed success in more than 90%. However, the
      effectiveness is design dependent, and the long-term effectiveness understandably
      is questioned as reports of mechanical failure begin to emerge.

PMID- 15577473
TI  - Biomechanics of large femoral heads: what they do and don't do.
AB  - The stability and durability of total hip reconstruction is dependent on many
      factors that include the design and anatomic orientation of prosthetic
      components. An analysis of femoral component head size and acetabular component
      orientation shows an interdependency of these variables and joint stability.
      Increased femoral component head size can increase hip stability by increasing
      the prosthetic impingement-free range of hip motion and by increasing the
      inferior head displacement required before hip dislocation. Increasing the
      femoral head size from 22 mm to 40 mm increases the required displacement for
      dislocation by about 5 mm with the acetabular component at 45 degrees of
      abduction; however, increasing acetabular component abduction greatly diminishes
      this stability advantage of larger femoral heads. Vertical acetabular component
      orientation and femoral component head subluxation are each predicted to more
      than double the tensile stress with acetabular component polyethylene compared
      with components at 45 degrees of abduction. With a desirable acetabular component
      orientation, the use of larger femoral heads may result in improved joint
      stability and durable use of polyethylene. With high abduction acetabular
      component orientation, the use of larger femoral heads contributes little to
      joint stability and contributes to elevated stress within the polyethylene that
      may result in implant failure.

PMID- 15577474
TI  - Prevention and treatment of dislocation after total hip replacement using large
      diameter balls.
AB  - The purpose of this study was to review safety and efficacy of total hip
      arthroplasty using large-diameter femoral heads in treatment and prevention of
      dislocation. One hundred forty hips in 135 patients were replaced using femoral
      heads at least 36 mm in diameter. The average age of the patients was 61.6 years.
      The patients were grouped into three categories depending on their diagnoses:
      recurrent dislocations from previous total hip replacements (Group 1; 29 hips);
      revision surgeries not including revisions for dislocations (Group 2; 54 hips);
      and primary surgeries (Group 3; 57 hips). The average followup was 5.5 years
      (range, 1-17 years). A total of 16 hips were revised: six for instability, four
      for fracture or disassociation of a conventional polyethylene liner, three for
      aseptic loosening of the socket, and three for sepsis. One hip from Group 1
      dislocated at 12.5 years postoperatively, was treated with closed reduction, and
      since has been nonrecurring. UCLA hip scores all improved significantly. The
      prevalence of dislocation varied among the three groups, with 13.7% for Group 1,
      1.8% for Group 2, and 3.5% for Group 3. The failure in the six cases that
      required revision for instability was attributable to poor socket orientation.
      All the hips became stable after revision without the use of a constrained
      acetabular liner. Large-diameter femoral heads provide additional stability not
      only for patients with recurrent dislocations, but also for patients having
      revision. The new, more wear-resistant bearings now enable the surgeon to extend
      the use of big femoral heads to primary total hip arthroplasty. Metal-on-metal
      seems to be the material of choice for a bone-conserving reconstruction with
      large femoral heads.

PMID- 15577475
TI  - Use of a constrained tripolar acetabular liner to treat intraoperative
      instability and postoperative dislocation after total hip arthroplasty: a review
      of our experience.
AB  - Constrained acetabular components have been used to treat certain cases of
      intraoperative instability and postoperative dislocation after total hip
      arthroplasty. We report our experience with a tripolar constrained component used
      in these situations since 1988. The outcomes of the cases where this component
      was used were analyzed for component failure, component loosening, and
      osteolysis. At average 10-year followup, for cases treated for intraoperative
      instability (2 cases) or postoperative dislocation (4 cases), the component
      failure rate was 6% (6 of 101 hips in 5 patients). For cases where the
      constrained liner was cemented into a fixed cementless acetabular shell, the
      failure rate was 7% (2 of 31 hips in 2 patients) at 3.9-year average followup.
      Use of a constrained liner was not associated with an increased osteolysis or
      aseptic loosening rate. This tripolar constrained acetabular liner provided total
      hip arthroplasty construct stability in most cases in which it was used for
      intraoperative instability or postoperative dislocation.

PMID- 15577476
TI  - Asymptomatic osteonecrosis: should it be treated?
AB  - Currently, there is no consensus regarding the treatment of precollapse
      osteonecrosis, particularly for asymptomatic osteonecrosis. With approximately
      10,000 to 20,000 new cases of osteonecrosis a year, no single surgeon or center
      has the kind of experience that is able to address the most important questions
      concerning this disease. The literature strongly documents that symptoms of
      osteonecrosis will progress. Although the literature also supports the
      progression of asymptomatic osteonecrosis to symptomatic osteonecrosis on to
      collapse, that support is less convincing. Progression is proportional to lesion
      size, with small lesions (< 15% of femoral head involvement by volume) unlikely
      to progress. Although the results of core decompression have been somewhat
      controversial, the weight of the literature supports both the efficacy and safety
      of the procedure. The decision to treat osteonecrosis with core decompression is
      primarily based upon lesion size and stage of disease and does not necessarily
      depend on whether the patient is symptomatic. As large lesions (> 30% of the
      femoral head) are less likely to be successfully treated by core decompression
      and small lesions (< 15% of the femoral head) are less likely to progress,
      asymptomatic lesions within these ranges can be observed. The literature supports
      the position that moderately sized lesions (15-30% of the femoral head) should be
      treated by core decompression (with or without bone grafting).

PMID- 15577477
TI  - Core decompression of the femoral head for osteonecrosis using percutaneous
      multiple small-diameter drilling.
AB  - Osteonecrosis is a disease with a wide ranging etiology and poorly understood
      pathogenesis seen commonly in young patients. Core decompression has historically
      been used in patients with small-sized or medium-sized precollapse lesions in an
      attempt to forestall disease progression. Typically, an 8-10 mm wide cannula
      trephine is used to do this procedure. The authors report on a new technique
      using multiple small drillings with a 3-mm Steinman pin to effectuate the core
      decompression. In this report, there were 32 of 45 hips (71%; 35 patients) with a
      successful clinical result at a mean followup of 2 years (range, 20-39 months).
      Twenty four of 30 Stage I hips (80%; 23 patients) had successful outcomes
      compared with 8 of 15 Stage II hips (57%; 12 patients) with no surgical
      complications occurring with this technique. This procedure is technically
      straightforward and led to minimal morbidity with no surgical complications. It
      may be effective in delaying the need for total hip arthroplasty in young
      patients with early (precollapse) stages of femoral head osteonecrosis.

PMID- 15577478
TI  - Treatment of osteonecrosis of the femoral head with core decompression and human
      bone morphogenetic protein.
AB  - A retrospective evaluation was done of 15 patients (17 hips) with symptomatic
      osteonecrosis of the hip treated with core decompression combined with an
      allogeneic, antigen-extracted, autolyzed fibula allograft and 50 mg of partially
      purified human bone morphogenetic protein and noncollagenous proteins. The
      average duration of clinical followup of the patients was 53 months (range, 26-94
      months). The osteonecrotic involvement of the hip was classified by plain
      radiographs using a modification of the Ficat staging system and MRI evaluations.
      Fifteen hips were classified as Ficat Stage IIA, one hip (one patient) was
      classified as Ficat Stage IIB, and one hip (one patient) was classified as Ficat
      Stage III. Fourteen hips had involvement of 50% or less of the femoral head and
      2/3 or less involvement of the weight-bearing surface of the femoral head, based
      on a magnetic resonance imaging evaluation. The procedures were a clinical
      success in 14 of 15 hips (93%; 13 patients) with Stage IIA disease. Three of 17
      hips (three patients) had radiographic progression (Ficat Stages IIA, IIB, and
      III) of the femoral head and were converted to total hip replacements. Only one
      of seven hips (six patients) with 50% or less involvement of the femoral head and
      between 1/3 and 2/3 of the weightbearing surface of the femoral head developed
      radiographic progression of the femoral head. There was no radiographic
      progression in the 3 hips with less than 1/3 involvement of the weightbearing
      surface of the femoral head. Further evaluation of the potential efficacy of bone
      morphogenetic protein is required in randomized trials.

PMID- 15577479
TI  - Outcome of hemiresurfacing in osteonecrosis of the femoral head.
AB  - Hemiresurfacing of the femoral head for treatment of osteonecrosis has been
      proposed as a reasonable alternative to total hip arthroplasty. The results of 59
      patients with Ficat Stage III osteonecrosis done by a single surgeon are
      reviewed. At an average followup of 4.5 years, 16 patients were considered
      failures because of conversion to total hip arthroplasty or considerable groin
      pain requiring medication. Failure did not correlate with age, body mass index,
      preoperative length of symptoms, acetabular articular cartilage status at the
      time of surgery, or cause of the underlying disease. The only factor associated
      with failure was a lower preoperative Harris hip score. Conversion of the failed
      implants to total hip arthroplasty was straightforward, confirming the
      conservative nature of the procedure. However, pain relief and recovery after
      resurfacing are less reliable than that associated with total hip arthroplasty.
      This procedure may be appropriate for patients younger than 30 years, given the
      ease of conversion to THR if failure occurs. The patient should be counseled
      regarding expectations.

PMID- 15577480
TI  - Total resurfacing for osteonecrosis of the hip.
AB  - With the resurgence of metal-on-metal bearings, there is renewed interest in
      total hip resurfacing. A cementless acetabular component used for resurfacing
      with a wall thickness of fewer than 5 mm is comparable in size to acetabular
      components used for total hip replacement. The fixation of a porous-ingrowth
      acetabular component used for resurfacing has been shown to be reliable and
      durable. There are few clinical reports of total hip resurfacing that stratify
      results by diagnosis. However, available evidence indicates that the pain relief,
      function, and activity after total hip resurfacing for osteonecrosis are superior
      to the results reported for hemiresurfacing and similar to the results of total
      hip replacement. Femoral-side failure is the main issue occurring with total
      resurfacing for osteonecrosis, and the femoral side failure rate is higher than
      that of hemiresurfacing. There are no simple guidelines for the extent of femoral
      head necrosis that are compatible with successful resurfacing. Refined patient
      selection and surgical technique can improve the outcomes and durability of total
      hip resurfacing for osteonecrosis.

PMID- 15577481
TI  - Arthroscopic intervention in early hip disease.
AB  - Advancement in diagnostic and therapeutic applications for hip arthroscopy have
      dispelled previous myths about early hip disease. Arthroscopic findings have
      established the following facts: Acetabular labral tears do occur; acetabular
      chondral lesions do exist; tears are most frequently anterior and often
      associated with sudden twisting or pivoting motions; and labral tears often occur
      in association with articular cartilage lesions of the adjacent acetabulum or
      femoral head, and if present for years, contribute to the progression of
      delamination process of the chondral cartilage. Magnetic resonance arthrography
      represents an improvement over conventional magnetic resonance imaging, it does
      have limitations when compared with direct observation. Although indications for
      hip arthroscopy are constantly expanding, the most common indications include:
      labral tears, loose bodies, chondral flap lesions of the acetabular or femoral
      head, synovial chondromatosis, foreign body removal, and crystalline hip
      arthropathy (gout, pseudogout, and others). Contraindications include conditions
      that limit the potential for hip distraction such as joint ankylosis, dense
      heterotopic bone formation, considerable protrusio, or morbid obesity.
      Complication rates have been reported between 0.5 and 5%, most often related to
      distraction and include sciatic or femoral nerve palsy, avascular necrosis, and
      compartment syndrome. Transient peroneal or pudendal nerve effects and chondral
      scuffing have been associated with difficult or prolonged distraction. Meticulous
      consideration to patient positioning, distraction time and portal placement are
      essential. Judicious patient selection and diagnostic expertise are critical to
      successful outcomes. Candidates for hip arthroscopy should include only those
      patients with mechanical symptoms (catching, locking, or buckling) that have
      failed to respond to conservative therapy. The extent of articular cartilage
      involvement has the most direct relationship to surgical outcomes. Improvements
      in technique and instrumentation have made hip arthroscopy an efficacious way to
      diagnose and treat a variety of intra-articular problems.

PMID- 15577482
TI  - Magnetic resonance arthrography versus arthroscopy in the evaluation of articular
      hip pathology.
AB  - In this study, we compared magnetic resonance arthrography results with hip
      arthroscopy findings to assess the diagnostic value of this imaging technique in
      evaluating acetabular labral tears and concurrent articular hip pathology. One
      hundred one consecutive patients (102 hips) with a clinical diagnosis of
      acetabular labral tear were assessed using magnetic resonance arthrography and
      had hip arthroscopy after failing to improve with nonoperative treatment.
      Magnetic resonance arthrography detected 71 of 93 (76%) acetabular labral tears
      (92 patients) with five false positive studies in five patients (4.9%). Articular
      cartilage findings diagnosed by magnetic resonance arthrography were confirmed by
      arthroscopy in 64 hips in 64 patients (62.7%). With respect to labral pathology,
      magnetic resonance arthrography showed a sensitivity of 71%, specificity of 44%
      positive predictive value of 93%, negative predictive value of 13%, and accuracy
      of 69%. With respect to articular cartilage pathology, magnetic resonance
      arthrography had a sensitivity of 47%, specificity of 89%, positive predictive
      value of 84%, negative predictive value of 59%, and accuracy of 67%. Although
      magnetic resonance arthrography is an excellent positive predictor in diagnosing
      acetabular labral tears and articular cartilage abnormalities, it has limited
      sensitivity. A negative imaging study does not exclude important intra-articular
      pathology that can be identified and treated arthroscopically.

PMID- 15577483
TI  - Osseous abnormalities and early osteoarthritis: the role of hip impingement.
AB  - The purpose of this study was to establish that anterior hip impingement,
      secondary to an anterior femoral offset deficiency from a pistol-grip deformity,
      was a common etiology of hip disorders. This impingement results in a spectrum of
      injury ranging from anterior hip pain, labral tears, damage to the acetabular
      articular cartilage and idiopathic arthritis. This was accomplished through three
      separate but closely related studies: (1) an arthroscopic labral tear study of 38
      patients who had hip arthroscopy for a labral tear (2) a hip cheilectomy study of
      10 patients who had a cheilectomy for anterior femoroacetabular impingement and
      (3) an idiopathic arthritis study of 200 consecutive patients having THA. In all
      three studies, a common etiology was identified. Repetitive anterior
      femoroacetabular impingement resulted in anterior groin pain, labral tears,
      chondral damage and eventually arthritis. This impingement was caused by a pistol
      grip deformity of the proximal femur in 97% of the cases in the arthroscopic
      labral study and 100% of the cases in the idiopathic arthritis study. The
      identification of anterior hip impingement as a cause of labral tears and
      idiopathic arthritis may allow surgeons to correct it early in its natural
      history and delay or prevent end-stage arthritis.

PMID- 15577484
TI  - Debridement of the adult hip for femoroacetabular impingement: indications and
      preliminary clinical results.
AB  - Untreated femoro-acetabular impingement is a common cause of osteoarthrosis of
      the hip. Surgical debridement of the adult hip with femoro-acetabular impingement
      recently has been advocated with the aim of relieving symptoms and slowing or
      halting progression of the arthrosis. At surgery, femoral sources of impingement
      are relieved by debriding the aspheric peripheral portion of the femoral head and
      the adjacent femoral neck. Acetabular sources of impingement can be relieved by
      debridement of the anterior rim. The most fundamental questions concerning these
      procedures relate to the preoperative and postoperative function, postoperative
      survivorship of these hips and the incidence of osteonecrosis. The current study
      assesses a group of 23 hips in 23 patients treated by surgical debridement for
      impingement. Twenty-two patients were treated by full surgical dislocation and
      one patient was treated by relief of impingement without dislocation. Followup
      ranged from a minimum of 2 years to 12 years. At most recent evaluation, seven
      patients had been converted to total hip arthroplasty, one had arthroscopic
      debridement of a recurrent labral tear, and 15 patients have had no further
      surgery. No hips developed osteonecrosis. Of the seven patients who had to have
      their procedure converted to total hip arthroplasty, three of these hips failed
      early and four patients' hips recovered and functioned well and subsequently
      deteriorated with total hip arthroplasty done between 6.4 and 9.5 years after
      debridement. Hips at greatest risk of failure have advanced arthrosis or a
      combination of impingement and instability preoperatively. The procedure
      effectively treats hips with impingement and without considerable secondary
      arthrosis or instability.

PMID- 15577485
TI  - Acetabular osteotomy: indications and results.
AB  - Acetabular osteotomy is the treatment of choice for young patients with
      symptomatic structural abnormalities of the acetabulum in the absence of severe
      secondary degenerative changes. These disorders can include hip instability from
      classic developmental dysplasia or posttraumatic acetabular dysplasia, hip
      impingement from retrotorsional acetabular deformities, or rarely, posttraumatic
      problems. During the last 15 years, various techniques of acetabular
      reorientation have evolved, making the procedure reliable, reproducible, and
      durable. In this report, the current indications and results of acetabular
      osteotomy in patients with symptomatic acetabular structural problems will be
      discussed.

PMID- 15577486
TI  - Reasons for revision hip surgery: a retrospective review.
AB  - The purpose of this study was to determine the indications for contemporary
      revision hip surgery in a consecutive series of patients. We retrospectively
      reviewed the clinical records and radiographs of 439 revision hip surgeries done
      between 1996 and 2003. Fifty-five percent of the surgeries were for aseptic
      loosening, 14% were for instability, 13% were for osteolysis around a well-fixed
      implant, 7% were for infection, 5% were for periprosthetic fracture, 3% were for
      conversion of a hemiarthroplasty, 1% was for psoas impingement, 1% was for loose
      recalled implants, and 1% was for implant fracture. As expected, aseptic
      loosening was the most common reason for revision surgery. Instability was a
      common reason for early revision whereas revision for osteolysis around a well
      fixed implant was a more common reason for late revision.

PMID- 15577487
TI  - The current role of structural grafts and cages in revision arthroplasty of the
      hip.
AB  - Treating large segmental acetabular defects that comprise more than 50% of the
      acetabulum is one of the most difficult challenges in revision arthroplasty of
      the hip. One of the surgical options is a structural acetabular allograft. Unless
      these allografts are protected by a cage that extends from ilium to ischium,
      there is an unacceptable incidence of graft failure. The cage allows
      reconstruction at the correct anatomic level. It provides a scaffold for bone
      grafting (structural and morsellized). The use of cement to stabilize the cup
      allows the surgeon to adjust the cup position independent of the cage. The
      current generation of cages does not provide biologic fixation and with time may
      loosen or fracture. Recent experience with a combination of a trabecular metal
      shell protected by a cage may offer a more favorable environment for bone
      grafting with permanent biologic fixation of the cup cage construct.

PMID- 15577488
TI  - Modular porous metal augments for treatment of severe acetabular bone loss during
      revision hip arthroplasty.
AB  - Modular acetabular augments were implanted in 16 patients (16 hips) for support
      of an uncemented hemispheric acetabular component during revision acetabular
      reconstruction. Based on the classification of Paprosky, acetabular bone defects
      were classified as 2A in one hip, 2B in three hips, 2C in one hip, 3A in five
      hips, and 3B in six hips. Preoperatively, the prosthetic femoral head centers
      were located at a mean horizontal distance of 18.6 mm (range, -3-46 mm), and a
      mean vertical distance of 27.6 mm (range, -16-52 mm) from the approximate femoral
      head center. Postoperatively, the prosthetic femoral head centers were located at
      a mean horizontal distance of 10.4 mm (range, 1-25 mm), and a mean vertical
      distance of 7.4 mm (range, -15-25 mm). At final followup, no implant had evidence
      of migration or loosening. At early clinical followup, this modular acetabular
      augment system seems helpful in acetabular reconstructions that cannot be treated
      with an uncemented hemispheric cup that would have required other forms of
      treatment such as structural allografts, acetabular cages, bilobed acetabular
      components, or custom acetabular components. Longer term followup is required to
      determine whether there are untoward effects of using a modular acetabular
      reconstructive system.

PMID- 15577489
TI  - Use of custom triflanged acetabular components in revision total hip
      arthroplasty.
AB  - Difficulty persists in consistently treating massive acetabular defects in
      revision total hip arthroplasty. A relatively new treatment option for these
      complex cases is a custom triflanged acetabular component created from anatomic
      data derived from a computed tomography scan of the pelvis. The custom triflanged
      acetabular component achieves fixation on the remaining ilium, ischium, and pubis
      with multiple fixation screws while the acetabular defect is filled with
      cancellous allograft bone. A retrospective review was done of 26 hips (26
      patients) with massive periacetabular bone loss (Paprosky Type 3B) reconstructed
      with a custom triflanged acetabular component. Twenty-three of 26 patients
      (88.5%) were considered clinically successful at short-term followup (average, 54
      months; range, 24 to 85 months), with stable fixation and reconstruction of
      periacetabular bone. Three failures occurred from loss of ischial fixation in two
      patients with a preoperative pelvic discontinuity and one patient with severe
      osteopenia. These devices should be used with caution in patients with a
      preoperative pelvic discontinuity unless additional column plating is done.

PMID- 15577490
TI  - Femoral fixation in the face of considerable bone loss: cylindrical and
      extensively coated femoral components.
AB  - One option for dealing with considerable femoral bone deficiency at revision
      surgery is the use of extensively porous coated cobalt-chrome cylindrical stems.
      This technique has been shown to be a reliable, technically straightforward
      method that can be applied to all but the most severe femoral structural defects.
      Very high rates of osseointegration and durability of fixation are obtained when
      simple principles are followed. The key to success is obtaining initial endosteal
      diaphyseal fixation over 5 cm-7 cm. To achieve this, adequate exposure and
      accurate bone preparation are essential. The limitations of this technique relate
      directly to the severity of bone loss, which can be easily predicted on plain
      preoperative radiographs. For Paprosky 3B and 4 defects, other options such as
      allograft prosthetic composites, impaction grafting, or alternate modes of distal
      fixation should be considered.

PMID- 15577491
TI  - Major femoral bone loss in revision total hip arthroplasty treated with tapered,
      porous-coated stems.
AB  - Clinical results of revision total hip arthroplasty using fully porous-coated
      tapered titanium stems to treat severe proximal femoral bone loss were evaluated
      in a retrospective review of 39 patients (45 hips). The bone was reinforced with
      cables in 39 hips, and in 14 hips strut allografts were added. Fixation was
      successful in 44 hips, and one hip required revision to treat undetected fracture
      and migration of the stem. All the others had radiographic evidence of bone
      attachment. Neither bone atrophy nor reconstitution was noted. Three patients (3
      hips) had mild thigh pain, but the others had no pain related to the femoral
      component. Eight hips dislocated; one resolved and seven had recurrent
      dislocation that was treated with a constrained acetabular component,
      capsulorrhaphy, or liner reorientation. Ten patients (12 hips) used a walker and
      10 patients (12 hips) used a cane at the last postoperative visit. Whereas
      fixation was successful with this surgical technique, complications related to
      deficiency of the soft tissue structures were common.

PMID- 15577492
TI  - Femoral fixation in the face of considerable bone loss: the use of modular stems.
AB  - Considerable femoral bone loss can be encountered in the multiply revised total
      hip arthroplasty patient. Deficient proximal bone requires either a bulk
      allograft or a femoral component that allows stable distal fixation. Extensively
      coated stems have shown excellent results for many revisions but have shown
      higher rates of failure among patients with femoral remodeling in retroversion,
      an enlarged endosteal diameter, or an ectatic canal. A modular tapered stem is an
      alternative in this subset of patients. A modular tapered implant provides axial
      and rotational stability through the use of distal splines, and the proximal body
      segments can allow independent adjustment of leg length, offset, and anteversion.

PMID- 15577493
TI  - Learning curve for the two-incision total hip replacement.
AB  - Recently there has been increased interest in doing total hip replacement through
      small incisions. One such technique is the two-incision approach. After initial
      investigations into its feasibility, Zimmer developed a training program for
      surgeons interested in doing the so called MIS 2-Incision Hip Procedure. An
      "index case" study was initiated to track the early experiences of trained
      surgeons, which includes 159 surgeons who have completed such training and
      recorded data on their initial cases. The purpose of this report is to present
      the data available from this index case study regarding the process of developing
      proficiency with the two-incision total hip replacement. We found a significant
      decrease in the mean operative time and fluoroscopy time from the first to tenth
      case. Key complications did not show a systematic decrease as a function of case
      number for the first ten cases. Clarification of the entire learning curve for
      this technique requires further investigation but may last beyond case ten for
      many surgeons. In addition, data from this study suggests that patient
      characteristics and surgeon experience have a significant effect on the
      prevalence of complications with the two-incision technique. The evolution of
      minimally invasive joint replacement is clearly in its infancy. Complication
      rates and the demonstrated learning curve may be altered by changes in training
      and surgical techniques.

PMID- 15577494
TI  - Rapid rehabilitation and recovery with minimally invasive total hip arthroplasty.
AB  - To assess the potential recovery rate of a minimally invasive total hip
      replacement technique with minimal soft tissue disruption, an accelerated
      rehabilitation protocol was implemented with weightbearing as tolerated on the
      day of surgery. One hundred consecutive patients were enrolled in this
      prospective study. Ninety-seven patients (97%) met all the inpatient physical
      therapy goals required for discharge to home on the day of surgery; 100% of
      patients achieved these goals within 23 hours of surgery. Outpatient therapy was
      initiated in 9% of patients immediately, 62% of patients by 1 week, and all
      patients by 2 weeks. The mean time to discontinued use of crutches, discontinued
      use of narcotic pain medications, and resumed driving was 6 days postoperatively.
      The mean time to return to work was 8 days, discontinued use of any assistive
      device was 9 days, and resumption of all activities of daily living was 10 days.
      The mean time to walk (1/2) mile was 16 days. Furthermore, there were no
      readmissions, no dislocations, and no reoperations. Therefore, a rapid
      rehabilitation protocol is safe and fulfills the potential benefits of a rapid
      recovery with minimally invasive total hip arthroplasty.

PMID- 15577495
TI  - Anterolateral mini-incision hip replacement surgery: a modified Watson-Jones
      approach.
AB  - Mini-incision total hip replacement seeks to eliminate some complications of
      traditional extensile exposure and also attempts to facilitate more rapid
      rehabilitation of patients after surgery. Different surgical approaches
      historically have been used to do hip replacement surgery. Anterior or
      anterolateral approaches have often been selected to decrease the risk of
      posterior dislocation. Traditional anterolateral approaches have divided the
      anterior portion of the gluteus medius and minimus and potentially jeopardized
      the superior gluteal nerve. These disadvantages have been associated with
      abductor weakness, prolonged limp and decreased patient satisfaction. To overcome
      these problems, a mini-incision approach was developed using the intermuscular
      plane between the gluteus medius and the tensor fascia lata. This intermuscular
      interval through a small incision provides good exposure for total hip
      replacement and preserves muscle integrity so that rehabilitation can be rapid
      and the posterior capsule remains intact so that posterior dislocation is less of
      an issue. The surgical technique for this new innovative approach is described in
      this article.

PMID- 15577496
TI  - A soft tissue attempt to stabilize the multiply operated glenohumeral joint with
      multidirectional instability.
AB  - Treating patients with multidirectional instability who have had multiple failed
      stabilization procedures is a challenging problem. These patients have disability
      from instability and pain. Final treatment may be glenohumeral narthrodesis. We
      report on the results of a soft tissue operation for treatment of
      multidirectional instability in multiply operated shoulders. Since 1994, 28
      patients have had what we term the kitchen sink operation for treatment of
      refractory multidirectional instability. After exclusion of patients with
      collagen abnormality, 10 patients who had at least three previous stabilizations
      were identified with recalcitrant multidirectional instability. The kitchen sink
      operation encompasses a humeral-based inferior capsular shift, Nicola biceps
      tenodesis, and coracohumeral ligament and rotator interval augmentation and/or
      reconstruction. All patients were immobilized for 8 weeks postoperatively.
      Minimum clinical and radiographic followup was 2 years (range, 2-6 years).
      Preoperatively, all patients had incapacitating pain and instability.
      Postoperatively, five patients (50%) had significant improvement of pain, and
      nine patients (90%) had successful reduction of instability. Four of the five
      patients with persistent disabling pain needed glenohumeral fusions. The kitchen
      sink operation is a final attempt to stabilize the shoulder with multidirectional
      instability. This procedure reduces instability (especially inferior) associated
      with multidirectional instability. However, pain remains unremitting in 50% of
      patients, therefore a glenohumeral arthrodesis may be needed as a last option.

PMID- 15577497
TI  - Histopathologic features of the acetabular labrum in femoroacetabular
      impingement.
AB  - This paper summarizes clinical and histopathologic findings derived from 25
      patients who had surgery for symptomatic femoroacetabular impingement. We
      explored if observed pathologic features were consistent with hypothesized
      mechanisms of injury, if severity of osteoarthritis and labral degeneration were
      associated, and if labral refixation would present an alternative. Clinically,
      all patients presented with limited range of motion at the hip attributable to
      pain and a positive impingement test. Magnetic resonance arthrography and
      surgical observations showed degenerated or ruptured labra or both in the
      anterior and/or superior regions of the acetabular rim (24 of 25 specimens) which
      correlated with pain provocation, limited range of motion, and anatomic
      deformities. Histologically, labra were mostly hyperplastic with disorganized
      cystic matrices. No inflammation was observed. Spatial distribution of
      degenerated labral matrices was not different for the two femoroacetabular
      impingement mechanisms. Labral degeneration and severity of osteoarthritis
      observed on radiographs did not correlate. In patients having only joint
      debridement, the labral matrix at the tip, near its vascular supply, was normal.
      Femoroacetabular impingement is a gentle chronic irritation of the labra located
      at the site of rupture that elicits a degenerative reaction. In early stages of
      the disease, the labral tip is not involved, providing the possibility of labral
      refixation after resection of the degenerated portion.

PMID- 15577498
TI  - Lessons learned from the hip and knee musculoskeletal outcomes data evaluation
      and management system.
AB  - In 1994 the American Academy of Orthopaedic Surgeons established an outcomes
      initiative. The Musculoskeletal Outcomes Data Evaluation and Management System
      had two goals: (1) to create validated patient-based functional health
      questionnaires that would become the gold standard for musculoskeletal research,
      and (2) to collect data from practicing orthopaedists using these instruments. We
      assessed the adequacy of the hip and knee portion of the Musculoskeletal Outcomes
      Data Evaluation and Management System data collection process to learn how to
      improve these processes. Database elements included demographic and clinical
      information and health and well-being scales. Only 715 records or 578 patients of
      the initial 2419 records (30%) had complete baseline and followup information for
      either hip or knee replacement procedure. Only 17% of the patients who had a knee
      replacement and 20% of the patients who had a hip replacement returned for
      followup between 7 and 9 months. The Musculoskeletal Outcomes Data Evaluation and
      Management System achieved its goal regarding the development of validated
      questionnaires, but the data collection component did not. The project's
      implementation and management were flawed. This experience offers the field of
      orthopaedics valuable lessons that can be applied to future large-scale data
      collection efforts.

PMID- 15577499
TI  - Revision total knee arthroplasty complication rates in Northern Illinois.
AB  - A paucity of population-based data exist which describe the rapid growth of
      revision total knee arthroplasties, changes in patient characteristics, or the
      association of hospital volume with complication rates. We analyzed whether
      inpatient complications for 2986 revision knee arthroplasties done on patients
      admitted to 63 hospitals in northern Illinois from 1993-1999 were correlated with
      volume of revision total knee arthroplasties. Coded complication rates for
      hospitals with less than seven, seven to 14, or greater than 14 annual procedures
      were compared using logistic regression to control for clinical and demographic
      characteristics of patients, hospital teaching status, and the proportion of the
      hospitals' patients discharged to rehabilitation facilities. Revision total knee
      arthroplasties increased 59%, and the overall complication rate declined from
      9.3% during 1993-1996 to 7.3% during 1997-1999 (p = .04). When compared with the
      lowest volume hospitals, medium-volume hospitals had higher complication rates,
      whereas the highest volume hospitals were not significantly different. The
      absence of volume-outcome effects may be related to the relatively high volume of
      primary knee arthroplasties done at almost all area hospitals, surgeon group
      coverage across multiple hospitals, and the small annual number of revision total
      knee arthroplasties done during these years.

PMID- 15577500
TI  - Survival data for 648 patients with osteosarcoma treated at one institution.
AB  - During the past 30 years, the orthopaedic oncology group at the Massachusetts
      General Hospital has treated 648 patients with osteosarcoma centrally located in
      the bone. Using records maintained in a specifically designed computer system, a
      study was done to assess the factors that seemed to influence the survival
      outcome. The overall survival for the entire series was 68% at an average
      followup of 6 +/- 4 years. Death occurred at a mean of 3 +/- 3 years. Patient
      gender had no effect, but age of the patient was correlated with survival data,
      with the poorest survival for the older patients. Surgical treatment had no
      effect on outcome, but the Musculoskeletal Tumor Society stage of the lesion, the
      presence of metastases or local recurrence, and the chemotherapeutic treatment
      (very dependent on the drugs available and adjuvant versus neoadjuvant
      administration at various decades) all had a profound effect. In addition,
      anatomic location, size of the tumor, and percentage of tumor cells killed after
      neoadjuvant chemotherapy all had an effect on outcome.

PMID- 15577501
TI  - Effective treatment of fracture-dislocations of the olecranon requires a stable
      trochlear notch.
AB  - Our goal with this study was to better define and characterize fracture
      dislocations of the olecranon and to provide additional data regarding
      complications and elbow function after operative treatment. Twenty-six patients
      with fracture-dislocations of the elbow were reviewed retrospectively. Ten had
      anterior and 16 had posterior fracture-dislocations. Five of 10 patients with
      anterior injuries and all of the patients with posterior injuries had an
      associated fracture of the coronoid process of the ulna. One of 10 patients with
      anterior and 13 of 16 patients with posterior injuries had fracture of the radial
      head. Only one patient had a true dislocation of the ulnohumeral joint. In the
      other 25 patients the articular surfaces remained apposed. All 26 patients were
      treated operatively and followed up for at least 3 years (average, 6 years). The
      results were good or excellent in 21 of 26 patients according to the system of
      Broberg and Morrey. The five unsatisfactory results were related to inadequate
      fixation of the coronoid with subsequent arthrosis (three patients), proximal
      radioulnar synostosis (three patients), and a subsequent fracture of the distal
      humerus (one patient). Fracture-dislocations of the olecranon occur in anterior
      and posterior patterns with specific injury characteristics and pitfalls. The key
      to effective treatment is stable restoration of the trochlear notch.

PMID- 15577502
TI  - Canine ovariohysterectomy and orchiectomy increases the prevalence of ACL injury.
AB  - To determine whether canine ovariohysterectomy or orchiectomy affects the
      prevalence of anterior cruciate ligament injury, we compared injury rates of
      anterior cruciate ligaments of animals that had gonadectomy and animals that were
      sexually intact as a function of gender, breed, or size. Records of 3218 dogs
      treated in one orthopaedic veterinary practice during a 2-year period were
      retrospectively reviewed. Anterior cruciate ligament injury, diagnosed by a
      history of acute hind limb lameness and by positive anterior drawer test, was
      confirmed at the time of surgery. The prevalence of anterior cruciate ligament
      rupture in all dogs was 3.48%. Females that had ovariohysterectomy and males that
      had orchiectomy had a significantly higher prevalence of anterior cruciate
      ligament rupture than the sexually intact dogs. Larger dogs had an increased
      prevalence of anterior cruciate ligament injury compared with smaller or medium
      sized dogs, with the increased rupture rates for sterilized animals holding
      across breeds and sizes. Sterilization of either gender increased the prevalence
      of anterior cruciate ligament injury, suggesting a potential effect of gonadal
      gender on prevalence of injury of this ligament.

PMID- 15577503
TI  - The ABJS presidential lecture, June 2004: our orthopaedic heritage: the American
      Civil War.
AB  - War, considered to be one of the greatest causes of human suffering, often spurs
      some of the greatest advances in medical treatments. In the United States, the
      Civil War was a catalyst for the development of trauma management, including
      general wound management, amputation techniques, triage, and transportation of
      wounded soldiers. The War, by necessity, also accelerated surgical knowledge and
      treatment of gunshot wounds of the extremities more than any previous event. The
      War also served as the impetus for the specialization of surgical skills,
      hospital systems, and medical data collection. Orthopaedic surgery, at the time
      of the War, was not as yet a recognized specialty in the United States. However,
      the Civil War played an important role in the specialty's heritage and the
      creation of specialty orthopaedic and prosthetic hospitals. Although many
      discoveries in the area of orthopaedic surgery were not discovered until the 20th
      century, many basic orthopaedic procedures and techniques were developed during
      this war that continue to be used today, including Buck's traction, plaster
      splints, and open treatment of contaminated wounds. The first recorded attempts
      at open reduction-internal fixation techniques for gunshot fractures occurred
      during the War. Resection arthroplasties, shell and bone fragment extraction, and
      various types of amputation were improved because of the large numbers of
      casualties.

PMID- 15577504
TI  - The 2003 Nicolas Andry Award. Orthopaedic gene therapy.
AB  - We review progress in the field of orthopaedic gene therapy since the concept of
      using gene transfer to address orthopaedic problems was initiated approximately
      15 years ago. The original target, arthritis, has been the subject of two
      successful Phase I clinical trials, and additional human studies are pending in
      rheumatoid arthritis and osteoarthritis. The repair of damaged musculoskeletal
      tissues also has proved to be a fruitful area of research, and impressive
      enhancement of bone healing has been achieved in preclinical models. Rapid
      progress also is being made in the use of gene transfer to improve cartilage
      repair, ligament healing, and restoration of various additional tissues,
      including tendon and meniscus. Other applications include intervertebral disc
      degeneration, aseptic loosening, osteoporosis, genetic diseases, and orthopaedic
      tumors. Of these various orthopaedic targets of gene therapy, tissue repair is
      likely to make the earliest clinical impact because it can be achieved with
      existing technology. Tissue repair may become one of the earliest clinical
      successes for gene therapy as a whole. Orthopaedics promises to be a leading
      discipline for the use of human gene therapy.

PMID- 15577505
TI  - The 2002 Marshall Urist Young Investigator Award Paper. Lumbar arthrodesis gene
      expression: a comparison of autograft with osteogenic protein-1.
AB  - Data from animals have revealed that osteogenic protein-1 induces solid
      intertransverse process fusion more reliably than autograft, and has motivated
      the question: What is the difference in the fusion bed environment engendered by
      the addition of osteogenic protein-1? To address this question, an established
      New Zealand White rabbit model of spinal arthrodesis was used to evaluate the
      effect of iliac crest autograft, and alternatively osteogenic protein-1, on
      cytokine gene expression in the developing spinal fusion mass. The autograft
      group and the osteogenic protein-1 group had a similar pattern of gene expression
      for most of the cytokines investigated, highlighting the finding that the
      application of one bone morphogenetic protein to the fusion bed results in nearly
      the same gene expression as that resulting from application of autologous bone.
      Some differences in cytokine expression were observed at the fusion bed with the
      addition of osteogenic protein-1. The increased level of expression of particular
      osteogenic, chondrogenic, and angiogenic growth factors at the later stages of
      fusion may be responsible for the improved rate of solid fusion with osteogenic
      protein-1 as compared with autograft alone. Sequences for bone morphogenetic
      protein-5 and bone morphogenetic protein-7 were determined, and their respective
      expression in the developing spinal fusion mass was observed for the first time.

PMID- 15577506
TI  - New technology and the orthopaedic surgeon: are you protecting your patients?
AB  - The treatment of patients with musculoskeletal disease will be revolutionized
      during the next two decades by advances in technology. Orthopaedic surgeons are
      eager to incorporate new technology into their practices to improve patient
      outcomes and practice efficiency. However, as the orthopaedic community embraces
      new technology and innovative surgical procedures, there is an increased need to
      consider issues of patient safety and to determine the best way to incorporate
      technology into our practices.

PMID- 15577507
TI  - Lower extremity swelling after treatment for thigh synovial sarcoma.

PMID- 15577508
TI  - Evaluation and treatment of spinal injuries in the patient with polytrauma.

PMID- 15577509
TI  - Pseudoseptic reactions to Hylan viscosupplementation: diagnosis and treatment.

PMID- 15577514
TI  - Velocity necessary for a BB to penetrate the eye: an experimental study using pig
      eyes.
AB  - PURPOSE: To determine the V-50 threshold velocity needed for a steel BB to
      penetrate the eye of a 230-pound pig. METHOD: BBs were shot at a distance of 10
      feet into the corneas of pig eyes with a pump-action BB gun. RESULTS: The V-50
      velocity for corneal penetration and serious disruption of the eye was found to
      be 246 ft/sec. CONCLUSION: Due to the nearly identical size and anatomy of the
      human eye to the pig eyes used in this study, it is felt that 246 ft/sec is a
      reasonable approximation of the velocity needed to penetrate the human eye.

PMID- 15577515
TI  - Detergent: an alternative approach to traditional bone cleaning methods for
      forensic practice.
AB  - Osteological assessment of human remains forms an essential part of forensic
      work, especially during the examination of extensively decomposed, dismembered,
      or burnt bodies. Currently employed methods for removal of adherent soft tissue
      reflect practices often used by museum curators, notably insect consumption,
      enzymatic maceration, or boiling of the bones, with subsequent manual removal of
      material. This study was designed to assess the effectiveness of detergents for
      the purpose of soft-tissue removal from animal-derived specimens. The results
      indicate that such a means is comparable to enzymatic maceration but with fewer
      health and safety issues and greater advantages regarding transportation and
      availability of materials when an investigator is in a fieldwork scenario.

PMID- 15577516
TI  - External injuries to the neck after free fall from great height.
AB  - Falls from great height are suicidal in most cases. Any antecedent trauma that
      would indicate an involvement of a third party should, however, be excluded in
      each case. Herein lies the difficulty in such cases since injuries prior to the
      fall which could be of criminal nature may be masked by the impact injuries.
      Injuries on unexposed parts of the body should always raise the suspicion of an
      involvement of a third party. This applies especially for neck injuries. By a
      retrospective analysis of 132 cases of falls from great height, the authors
      conclude, however, that neck injuries may occur after free fall from great height
      on a flat surface without antecedent trauma.

PMID- 15577517
TI  - Use of prostate specific antigen in the identification of semen in postmortem
      cases.
AB  - Over the past 20 years, the use of prostate specific antigen (PSA) as evidence of
      the presence of semen in forensic cases has been well established. In this study,
      we compared a commercially available immunoradiometric assay (IRMA) for the
      identification of PSA with the identification of spermatozoa in swabs obtained
      from the vagina of deceased females. There was agreement between the 2 methods in
      67 of the 80 cases (84%), including 18 cases where both the PSA was positive and
      sperm were observed microscopically. The remaining cases had 1 positive result
      and 1 negative result. We concluded that although there was substantial agreement
      between the presence of sperm and a positive PSA, there were enough discrepancies
      between the 2 methods (16%) to justify the use of both methodologies, if
      possible, to make the determination of sexual activity prior to death.

PMID- 15577518
TI  - What is the incidence and significance of "dry-lungs" in bodies found in water?
AB  - BACKGROUND: Drowning without aspiration of liquid, generally attributed to death
      from asphyxia while submerged and in laryngospasm, has been reported to occur in
      approximately 10% to 15% of drowning victims. OBJECTIVES: The occurrence of "dry
      drowning" recently has been questioned and the hypothesis developed that "dry
      lungs" in bodies found dead in the water could conceal more natural deaths than
      previously recognized. METHODS: Based on 578 selected adult victims who
      presumably drowned, we analyzed the correlation between the cases with a low
      combined lung/pleura liquid weight (< 1000 g and < 750 g) and a wide set of
      individual, circumstantial, and postmortem (PM) variables, using multivariate
      logistic regression analysis. Victims with lung weight < 1000 g were screened for
      long-QT syndrome (LQTS) founder mutations in KCNQ1 and KCNH2 genes. RESULTS: Of
      the 578 victims, 120 (20.7%) had a lung weight of < 1000 g, and 22 of these
      (3.8%) of < 750 g. Multivariate analysis showed a significant correlation for
      women (P < 0.001), for women aged 65 years or older (P < 0.001), and for men with
      prolonged PM submersion time (P < 0.001). "Normal" lungs were found in only 8
      (1.4%) victims. Low-weight (< 1000 g), overdistended lungs with no sign of liquid
      penetration were seen in 11 (1.9%). No LQTS founder mutations were detected.
      CONCLUSIONS: The actual incidence of death of persons found in water who have
      normal lungs or do not have penetration of liquid into their airways, based on
      our study, is much lower (below 2%) than currently assumed.

PMID- 15577519
TI  - Forensic ethnic identification of crania: the role of the maxillary sinus--a new
      approach.
AB  - Forensic pathologists may be asked to identify the ethnic group and gender of a
      cranium of unknown origin. An analysis of the maxillary sinus--its volume, shape,
      and dimensions in dried crania of different ethnic and gender groups (European
      and Zulu male and female)--was conducted to establish a new approach. A variation
      in maxillary sinus volume may mean a variation in anatomic landmarks between the
      groups. Ethnic and gender variations in the shape of the maxillary sinus of the
      crania were investigated. This research was further extended to predict the
      gender and ethnic group from an unknown cranium to make this research valuable to
      the fields of forensic pathology and anthropology. Helical, multislice computed
      tomography was performed using 1-mm coronal slices. The area for each slice was
      obtained by tracing the outline of each slice. The computed tomographic machine
      calculated a volume by totalling the slices for each sinus. Advanced computer
      methodology including a neural network was designed and applied to search for
      classification patterns in data. A discriminant analysis was performed to improve
      classification results. Ethnic and gender variations were found in the different
      groups, and the predictive role of the maxillary sinus in ethnic classification
      was established. It was found that European crania had significantly larger
      antral volumes than Zulu crania, and males had larger volumes than females.
      Dimensions of European sinuses were larger than those of Zulu sinuses. The medial
      antral wall of the sinus allowed for ethnic classification. The discriminant
      analysis allowed for a very successful 90% ethnic prediction, while gender
      prediction was ultimately 79%. The measurements taken and the formulae created in
      this research will be valuable to those in the field who are seeking to
      ethnically classify a cranium into one or another ethic group. This research aims
      to be an aid in identification, as well as a starting point for other scientific
      studies based on other ethnic groups. Perhaps its true value will lie in
      confirming ethnicity by adding to existing criteria. It must be noted that this
      classification is based on actual measurements and therefore eliminates the some
      of the subjectivity present in current methods of ethnic classification.

PMID- 15577520
TI  - Unusual torture methods and mass murders applied by a terror organization.
AB  - This study aims at describing autopsy findings of 19 victims killed by various
      torture methods applied by a terror organization after they had been kidnapped by
      this organization, as well as the unusual and unique binding style applied during
      these killings. The present study also aims at describing the unusual killing
      method of binding for literature and discussing international descriptions of
      torture.

PMID- 15577521
TI  - Acid violence: a burning issue of Bangladesh--its medicolegal aspects.
AB  - Throwing acid on others' face and body to cause grievous injuries is a barbaric
      act of vengeance. For the last few years, it has been on the rise in both urban
      and rural areas of Bangladesh. The perpetrators are mostly men and adolescent
      boys. The victims are girls and young females. The reasons for attacks are sexual
      advances from man, refusal of marriage proposal, and vengeance. Cheap and easy
      availability of acids makes it the most effective weapon for man to use against
      girls' or young women's faces to prove that they have no right to deny a man's
      proposal and is one of the extreme forms of repression and violation of women's
      right. The consequence of acid attacks on survivors brings dramatic change in
      their lifestyle. Most of them have to give up their education or work. Social
      isolation, fear of further attacks, and insecurity damage their self-esteem and
      confidence. Illiteracy, poverty, threats to further retribution, and ignorance
      about legal support increase their miseries. Gradual increase of acid attacks
      suggests that legal provisions and their enforcement are not adequate and
      effective. Social awareness, economic and psychologic support, rehabilitation,
      and strict enforcement of laws are key to combat acid violence in Bangladesh.

PMID- 15577522
TI  - Sudden suffocation by surgical sponge retained after a 23-year-old thoracic
      surgery.
AB  - A 70-year-old male patient with a 23-year-old history of right lower lung
      lobectomy for primary pulmonary adenocarcinoma (T1 N0 M0) presented with
      recurrent bronchopneumonia and purulent sputum. Pleural callus, lung abscess,
      bronchopleural fistula, and stitch granulomas were confirmed by chest x-ray,
      computed tomography scan, and bronchoscopy in the background of his complaints.
      An attempt to remove the bronchial purulent discharge and tissue sampling was
      made by using a flexible bronchoscope. The area of the lower trachea suddenly
      became clogged during bronchoscopic removal of the suspected piece of tissue
      (which later turned out to be organizing surgical gauze). The resuscitation
      following ventricular fibrillation failed to save the patient's life. The
      forensic postmortem examination confirmed the position of the foreign body
      extending from the abscess cavity, crossing the midline at carina and obstructing
      the lower trachea. This foreign body was a remnant of the surgical gauze left
      behind during a thoracic surgery 23 years ago.

PMID- 15577523
TI  - Pathologic findings in malignant hyperthermia: a case report and review of
      literature.
AB  - Malignant hyperthermia (MH) is a rare, potentially lethal disorder of skeletal
      muscle calcium homeostasis characterized by muscle contracture and life
      threatening hypermetabolic crisis following exposure to halogenated anesthetics
      and depolarizing muscle relaxants. Susceptibility to MH results from mutations in
      calcium channel proteins that mediate excitation-contraction coupling, with the
      ryanodine receptor calcium release channel (RyR1) representing the major locus.
      The mode of inheritance appears to be autosomal dominant with variable
      penetrance. The authors report the death of a 60-year-old white male with a
      history of low back pain. He had undergone 2 back surgeries previously, the first
      occurring 10 years prior to his current presentation. Both previous procedures
      were done under generalized anesthetic with no complications. Recently, he
      developed stenosis and presented for fusion of vertebrae L3 and L4. The procedure
      was performed under general anesthetic including sevoflurane, with no
      intraoperative complications. The anesthesiologist noted that, near the end of
      the 2-hour procedure, the decedent's CO2 levels were slightly elevated. After the
      procedure, the decedent was extubated, the temperature probe which had been
      recording normal values was removed, and he was rolled from ventral to dorsal
      position. He immediately became hypotensive and bradycardic. Lifesaving
      interventions were begun. Subsequently, he went into cardiac arrest, at which
      time the temperature probe was reinserted into the trachea, where it read a body
      temperature of 109 degrees F. Malignant hyperthermia protocol was initiated, and
      interventions continued for over 2 hours, at which time they failed. At autopsy,
      the abdomen contained 1800 mL of blood, and bilateral hematomas were present in
      the psoas muscles. The authors present this case of clinically apparent malignant
      hyperthermia, discuss how to approach such a case, the gross and microscopic
      findings, ancillary studies, and a review of the literature.

PMID- 15577524
TI  - Spontaneous intracerebral hemorrhage related to methamphetamine abuse: autopsy
      findings and clinical correlation.
AB  - A healthy 31-year-old male abstinent from drug abuse during his recent
      incarceration developed slurred speech, a severe headache, and left-sided
      hemiparesis prior to his eventual death 9.5 hours after inhalation of
      methamphetamine. On postmortem examination, inspection of the brain revealed
      bilateral subarachnoid hemorrhage, with a prominent intralobar hemorrhage
      centered within the right frontal cerebral hemisphere. No evidence of vasculitis,
      infarction, intraventricular hemorrhage, or ruptured aneurysm could be observed.
      While this is not the first report of a methamphetamine-related stroke, this
      report describes the autopsy findings of an intracerebral hemorrhage secondary to
      methamphetamine abuse on autopsy and compares the findings and antemortem history
      to previously reported methamphetamine cerebral vascular deaths.

PMID- 15577525
TI  - An unusual fatality in a child due to oxycodone.
AB  - An unusual fatality secondary to oxycodone in a child is reported. A 2-year-old
      female child was conveyed to a local hospital after exhibiting signs of rubbing
      of the mouth and staggering. A hospital toxicological immunoassay screen for
      drugs of abuse and tricyclic antidepressants was performed on a urine sample and
      reported as negative. She was discharged and found unresponsive the next morning.
      She was conveyed to a second hospital in full cardiopulmonary arrest and despite
      resuscitative efforts, was pronounced dead upon arrival. An autopsy was performed
      and postmortem specimens were submitted and screened for drugs using mainly
      chromatographic techniques. Quantitation was achieved by gas chromatography with
      nitrogen phosphorus detection. Confirmation was performed by gas
      chromatography/mass spectrometry. Oxycodone was the only drug detected in the
      following concentrations: heart blood, 1.36 mg/L; gastric contents, 7.33 mg in 33
      mL (222.34 mg/L); liver, 0.2 mg/kg; and urine, 47.23 mg/L (47,230 ng/mL). In
      addition, immunoassay testing of the urine was positive for the opiate class of
      drugs. This case report demonstrates an unusual cause of death in a young child
      with emphasis on potential limitation in hospital urine screening tests and the
      importance of complete forensic toxicological testing in all child deaths.

PMID- 15577526
TI  - Pellagra: a rare disease observed in a victim of mental and physical abuse.
AB  - Lesions of the brain stem and cerebellum due to nutritional deficiencies are
      mostly seen in chronic alcohol abuse and more rarely in severe malnutrition. We
      report the case of a 27-year-old woman, found dead in the family flat. She
      presented cachexia (167 cm, 25 kg) and multiple hematomas of the limbs.
      Postmortem examination revealed lesions due to peritonitis. Neuropathological
      examination showed severe atrophy of the corpus callosum and central neuronal
      chromatolysis, which are observed in pellagra. Inflammatory colitis or celiac
      disease was not found. Toxicological analysis was negative, in particular no
      alcohol absorption. Pellagra, which is due to nicotinamide deficiency, is a
      disease rarely seen in this country. In this case, nutritional deficiency was the
      consequence of failure to eat in a context of abuse. The woman was born of an
      incestuous relationship and presented intellectual retardation due to poor
      affective relations with her mother.

PMID- 15577527
TI  - A case study of the suicide of Luis Mendes France, in Bordeaux, in 1695.
AB  - After being condemned and imprisoned in Lisbon by the Portuguese Inquisition,
      Luis Mendes de Franca exiled himself in late 1683 to France, where his
      descendants adopted the family name Mendes France. In 1695, at the age of 55
      years, Luis Mendes committed suicide in Bordeaux by a pistol shot that
      decapitated him. The inquest conducted at that time concluded that Luis Mendes
      was insane and thus not guilty of the crime of suicide. We hypothesize that he
      used a flint stone-type pistol loaded with an extraordinarily large quantity of
      black gunpowder. Using available information on historic firearms, ammunition,
      and powder, coupled with the preserved testimony of historic figures, we propose
      a reconstruction of this drama and a diagnostic approach to the psychiatric
      aspects of the suicide.

PMID- 15577528
TI  - Tissue distribution of intubation-related lidocaine in brain-dead patients.
AB  - Tissue distribution of lidocaine that was used for endotracheal intubation during
      cardiopulmonary resuscitation (CPR) was measured in 3 patients who were brain
      dead or near brain death. Case 1 was a 69-year-old female whose heartbeat was
      restored by CPR but stopped 10 hours later. The lidocaine ratios of cerebrum to
      blood (2.04) and diencephalon to blood (1.01) were within ranges of those found
      in non-brain-dead patients. Case 2 was a 77-year-old female whose heart resumed
      beating after CPR but stopped 66 hours later. The lidocaine ratios of cerebrum to
      blood (5.69), diencephalon to blood (18.7), and cerebellum to blood (11.3) were
      much higher than those in non-brain-dead patients. Case 3 was a 48-year-old male
      who had cardiopulmonary arrest following an acute subarachnoid hemorrhage. His
      heart resumed beating after resuscitation but ceased beating 114 hours after
      admission. Lidocaine was detected only from the cerebrum, cerebellum, and blood
      clots in the superior sagittal sinus at levels of 0.028, 0.024, and 0.007 mug/g,
      respectively. Tissue distribution of intubation-related lidocaine in brain-dead
      patients is useful as supplementary data for reviewing hemodynamic changes in
      their brains during medical treatment.

PMID- 15577529
TI  - An unusual missile-type head injury caused by a stone: case report and
      medicolegal perspectives.
AB  - Missile head injury is predominantly caused by firearms; however, small blunt
      objects such as a stone can be propelled into the air and cause a low-velocity
      type missile injury, as described in this case report. Since the cerebral damage
      in low-velocity missile injuries is usually focal, there might not be disturbance
      of consciousness until secondary brain damage occurs; therefore, adequate medical
      supervision is necessary to prevent and treat potentially fatal complications in
      a timely manner. This is a rare case of a penetrating missile wound of the head,
      most likely caused by the use of a stone propelled by a slingshot that penetrated
      the skull and lacerated the brain with the stone embedded within the substance of
      the brain. The deceased died at home 2 days later from focal suppurative
      meningitis with cerebral abscess formation and a subdural hemorrhage.

PMID- 15577530
TI  - Traumatic asphyxial deaths due to an uncontrolled crowd.
AB  - Nine people died of traumatic asphyxia due to an uncontrolled crowd at a
      community basketball game in New York City in 1991. We reviewed the
      circumstances, postmortem findings, and the causes of death. The majority of
      people had petechiae of the conjunctivae and face consistent with chest
      compression. There were minimal superficial blunt injuries and no fractures or
      acute intoxications. These deaths are often incorrectly attributed to blunt force
      injuries, while the cause typically is asphyxia due to chest compression.

PMID- 15577531
TI  - Response to the National Association of Medical Examiners position paper on the
      certification of cocaine-related deaths.

PMID- 15577532
TI  - Sudden death, epilepsy and cerebral cortical heterotopia.

PMID- 15577533
TI  - International AIDS Conference: compliance issues.

PMID- 15577534
TI  - Special considerations in the initiation and management of antiretroviral therapy
      in individuals coinfected with HIV and hepatitis C.
AB  - BACKGROUND: Although hepatitis C (HCV) treatment efficacy has improved in recent
      years, the majority of HIV/HCV-coinfected individuals may not enjoy the full
      benefits of these treatments and appropriate HIV management is crucial. Evidence
      is accumulating regarding the impact of HIV/HCV coinfection on the response to,
      and safety and tolerability of, antiretroviral therapy (ART) in this population.
      METHODS: Computerized, English-language literature searches of MEDLINE and PubMed
      databases (January 1985 to May 2004) for studies of HIV and HCV infection in
      humans to examine critically (a) the impact of HCV on the HIV virologic and
      immunologic response to ART; (b) the safety and tolerability of ART in coinfected
      individuals; and (c) the relationship between immune suppression and immune
      restoration on hepatic injury. RESULTS: Three key messages emerged regarding the
      use of ART in HIV/HCV-coinfected individuals: (a) although HCV appeared to have
      no impact on HIV virologic response, the data are equivocal regarding immunologic
      response; (b) morbidities associated with HCV infection, such as insulin
      resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are also
      associated toxicities of ART, and (c) both immune suppression and restoration can
      contribute to the onset and acceleration of HCV-related liver disease.
      CONCLUSIONS: The CD4 cell count threshold for initiating ART in HIV/HCV
      coinfected patients may be higher because of the impact of immune suppression and
      restoration on the onset of HCV-associated liver disease and the possibility of a
      blunted immune response to ART at lower CD4 cell counts. Further, overlapping
      morbidity between HCV-related mitochondrial and metabolic disease manifestations
      and ART toxicities warrant careful attention by clinicians.

PMID- 15577535
TI  - Barriers to participating in an HIV vaccine trial: a systematic review.

PMID- 15577536
TI  - New CCR5 variants associated with reduced HIV coreceptor function in southeast
      Asia.
AB  - BACKGROUND: Despite multiple exposure to HIV-1, some individuals remain
      uninfected. This resistance has been associated with homozygosity for a 32 base
      pair deletion in the gene for the CCR5 receptor. This variant occurs frequently
      in Caucasians but is extremely rare in Asians or Africans. OBJECTIVE: To identify
      variations in CCR5 receptor gene that affect susceptibility to HIV infection in
      non-Caucasians. METHODS: CCR5 coding region polymorphisms were screened in three
      groups of Vietnamese subjects: 47 HIV-1 infected intravascular drug users, 50
      highly HIV-1-exposed but seronegative intravascular drug users and 37 HIV-1
      unexposed seronegative individuals. DNA was analysed by denaturing high
      performance liquid chromatography; this was followed by examination of the
      biochemical and HIV coreceptor properties of the coding regions. RESULTS: Five
      CCR5 coding region variants were identified in this Vietnamese population. The
      S185R, I254T and C269F mutations have not been previously described; G106R and
      R223Q have already been found in other Asian populations, but the functional
      properties of G106R is not known. These variants differed in biochemical and HIV
      coreceptor properties. S185R and I254T variants had receptor and coreceptor
      activities comparable to that of the wild type, whereas C269F and G106R behaved
      differently. This latter pair are poorly expressed at the cell surface, weakly
      bind macrophage inflammatory protein 1beta (CCL4) and RANTES (CCL5), and display
      reduced HIV-1 coreceptor efficiency. CONCLUSIONS: Among the five CCR5 variants
      found in this Vietnamese population, G106R and C269F displayed significant
      modifications of their receptor and coreceptor properties, which may contribute
      to susceptibility to HIV-1 infection and/or disease progression within this
      population.

PMID- 15577537
TI  - Incidence immunoassay for distinguishing recent from established HIV-1 infection
      in therapy-naive populations.
AB  - OBJECTIVE: To identify a specific marker of recent HIV-1 infection. DESIGN: The
      humoral immune response in individuals recently infected with HIV-1 was followed
      by analysing the antibody isotype-specific response generated to HIV-1 antigens
      in sequential samples collected during and following seroconversion. METHODS:
      Antibody isotype-specific HIV-1 Western blots were analysed to identify
      interactions indicative of recent HIV-1 infection. These responses were further
      quantified using an antibody isotype-specific enzyme-linked immunoabsorbent assay
      based on recombinant HIV-1 antigens. RESULTS: During maturation of the immune
      response to HIV-1 infection, a rapid and enduring IgG1 isotype response was seen
      to all the major proteins transcribed by env, gag and pol. An early transient
      peak of IgG3 reactivity to p24 was observed over an interval of approximately 1-4
      months following HIV-1 infection. The presence of IgG3 reactivity to p24
      permitted established infection to be distinguished from recently infected
      individuals during this time period. CONCLUSION: An assay for anti-p24 IgG3
      reactivity would provide an estimate of the incidence of HIV infection that may
      be applicable for epidemiological surveys as well as for monitoring new
      infections during vaccine trials and for managing treatment programmes.

PMID- 15577538
TI  - Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active
      antiretroviral therapy.
AB  - OBJECTIVE: To assess whether cellular HIV-1 DNA prior to highly active
      antiretroviral therapy (HAART) initiation predicts its outcome. DESIGN AND
      METHODS: Patients included all 51 hemophiliacs of the Greek component of the
      Multicenter Hemophilia Cohort Study who had initiated HAART and for whom
      cryopreserved lymphocyte samples before HAART initiation were available. Cellular
      HIV-1 DNA quantification was performed by a molecular beacon-based real-time PCR
      assay in multiple samples per patient with a median (interquartile range) follow
      up of 76 (45-102) weeks. RESULTS: The median (range) baseline HIV-1 DNA load was
      297 (< 10 to 3468) copies per 1 x 10(6) peripheral blood mononuclear cells.
      Baseline HIV-1 DNA load did not predict initial virological response (VR). None
      of the patients with initial VR and baseline HIV-1 DNA load at or below the
      median experienced a subsequent virological rebound, while the cumulative
      probability of virological rebound by week 104 was 55% among those with HIV-1 DNA
      load greater than the median (P < 0.008). Cellular HIV-1 DNA load was the only
      parameter associated with sustained virological response as shown by univariate
      or multivariate analyses [adjusted odds ratio (95% confidence interval) 0.197
      (0.048-0.801) per 1 log10 increase in DNA copies, P = 0.023]. CONCLUSION: Low
      cellular HIV-1 DNA load is a marker of sustained virological response in patients
      with initial VR and it can reliably predict the long-term success of HAART.

PMID- 15577539
TI  - A randomized study of emtricitabine and lamivudine in stably suppressed patients
      with HIV.
AB  - BACKGROUND: Once daily (QD) dosing facilitates regimen simplification and
      adherence to antiretroviral therapy. Emtricitabine (FTC) QD is a newly approved
      nucleoside reverse transcriptase inhibitor compared in this study to twice daily
      lamivudine (3TC BID). METHODS: Controlled, open label equivalence trial of 440
      HIV-1-infected patients with plasma HIV-1 RNA stably suppressed on a regimen of
      3TC 150 mg BID, stavudine or zidovudine, and a protease inhibitor or non
      nucleoside reverse transcriptase inhibitor. Patients were randomized to continue
      their current regimen or replace 3TC with FTC 200 mg QD. If HIV-1 RNA levels were
      </= pound 400 copies/ml at 48 weeks in Protocol 303, patients could continue on
      FTC in Protocol 350. The primary analysis was based on virologic failure and
      response defined by plasma HIV-1 RNA suppression below 400 copies/ml. RESULTS: At
      baseline, the mean CD4 cell count was 525 (FTC) and 533 x 10(6) cells/l (3TC). At
      week 48 in Protocol 303, the probability of virologic failure was low, 7% (FTC)
      and 8% (3TC), and the probability of sustained viral suppression at week 48 was
      equivalent between treatment arms at both the 50 and 400 copies/ml thresholds.
      The mean increase in CD4+ T-cell percentage was 2.5% (FTC) and 1.7% (3TC). In
      Protocol 350, the probability of virologic failure was 11% after 4 years on FTC
      containing highly active antiretroviral therapy (HAART). CONCLUSION: In stably
      suppressed patients, 200 mg emtricitabine QD was equivalent to 150 mg lamivudine
      BID. Emtricitabine-containing HAART was associated with a high rate of sustained
      virologic suppression during 4 years of follow-up.

PMID- 15577540
TI  - Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens
      with or without concurrent ritonavir.
AB  - OBJECTIVE: To determine the incidence of significant liver enzyme elevations
      following the initiation of protease inhibitor (PI)-based antiretroviral therapy
      (ART) with or without pharmacokinetic boosting with ritonavir (RTV), and to
      define the role of chronic viral hepatitis in its development. DESIGN:
      Prospective, cohort analysis of 1161 PI-naive, HIV-infected patients receiving
      RTV-boosted (lopinavir, indinavir and saquinavir) and unboosted PI-based ART
      (indinavir, nelfinavir) that had at least one liver enzyme measurement before and
      during therapy. METHODS: The incidence of grade 3 and 4 liver enzyme elevations
      among persons with and without hepatitis B and/or C co-infection treated with PI
      based ART were compared. Severe hepatotoxicity was defined as an increase in
      serum liver enzyme >/= 5-times the upper limit of the normal range or 3.5-times
      an elevated baseline level. RESULTS: The incidence of grade 3 or 4 elevations
      among PI-naive patients was: nelfinavir, 11%; lopinavir/RTV (200 mg/day), 9%;
      indinavir, 13%; indinavir/RTV (200-400 mg/day), 12.8%; and saquinavir/RTV (800
      mg/day), 17.2%. The risk was significantly greater among persons with chronic
      viral hepatitis (63% of cases); however, the majority of hepatitis C virus (HCV)
      infected patients treated with nelfinavir (84%), saquinavir/RTV (74%), indinavir,
      86%, indinavir/RTV (90%) or lopinavir/RTV (87%) did not develop hepatotoxicity.
      CONCLUSIONS: Our data suggest that the lopinavir/RTV is not associated with a
      significantly increased risk of hepatotoxity among HCV-infected and uninfected
      patients compared with an alternative PI-based regimen, nelfinavir. Accordingly,
      other medication-related factors (e.g, efficacy and non-hepatic toxicity) should
      guide individual treatment decisions.

PMID- 15577541
TI  - Hepatocellular carcinoma in HIV-infected patients: epidemiological features,
      clinical presentation and outcome.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in
      HIV-seropositive individuals. The aim of the study was to compare the main
      features of HCC in HIV-seropositive individuals with those in to HIV-negative
      patients. PATIENTS AND METHODS: All HIV-infected subjects with a diagnosis of HCC
      included in three cancer registry databases were enrolled in the study as cases.
      HCC cases that occurred in the province of Brescia, North Italy, in the period
      1995-1998 and all cases reported at the Italian Liver Cancer Project were
      enrolled as controls. All data were collected using a standardized case report
      form. The main clinical and epidemiological characteristics of patients with HCC
      and their survival were compared between HIV-positive and uninfected subjects.
      RESULTS: Forty-one HIV-infected subjects with HCC were identified. Multivariate
      analysis adjusted for age and sex identified an association between HIV infection
      and HCV infection [odds ratio (OR), 11; P = 0.005], and infiltrating tumours
      and/or extranodal metastasis at presentation (OR = 11.8; P < 0.001). HIV
      infection was independently associated with shorter survival (hazard ratio, 1.63;
      P = 0.015). CONCLUSIONS: HCC in HIV-infected patients is mainly associated with
      underlying chronic hepatitis C and has a more aggressive clinical course. Thus,
      preventative strategies (including the treatment of hepatitis C) should be
      implemented in the management of HIV/HCV-coinfected patients.

PMID- 15577542
TI  - Global overview of injecting drug use and HIV infection among injecting drug
      users.
AB  - OBJECTIVE: To provide global estimates of the prevalence of injecting drug use
      (IDU) and HIV prevalence among IDU, in particular to provide estimates for
      developing and transitional countries. METHODS: Collation and review of existing
      estimates of IDU prevalence and HIV prevalence from published and unpublished
      documents for the period 1998-2003. The strength of evidence for the information
      was assessed based on the source and type of study. RESULTS: Estimates of IDU
      prevalence were available for 130 countries. The number of IDU worldwide was
      estimated as approximately 13.2 million. Over ten million (78%) live in
      developing and transitional countries (Eastern Europe and Central Asia, 3.1
      million; South and South-east Asia, 3.3 million; East-Asia and Pacific, 2.3
      million). Estimates of HIV prevalence were available for 78 countries. HIV
      prevalence among IDU of over 20% was reported for at least one site in 25
      countries and territories: Belarus, Estonia, Kazakhstan, Russia, Ukraine, Italy,
      Netherlands, Portugal, Serbia and Montenegro, Spain, Libya, India, Indonesia,
      Malaysia, Myanmar, Nepal, Thailand, Viet Nam, China, Argentina, Brazil, Uruguay,
      Puerto Rico, USA and Canada. CONCLUSIONS: These findings update previous
      assessments of the number of countries with IDU and HIV-infected IDU, and the
      previous quantitative global estimates of the prevalence of IDU. However, gaps
      remain in the information and the strength of the evidence often was weak.

PMID- 15577543
TI  - Factors associated with a decrease in the prevalence of drug resistance in newly
      HIV-1 infected individuals in Montreal.
AB  - OBJECTIVE: A decrease in the prevalence of drug resistance (DR) has been observed
      among recently infected (RI) individuals in Montreal. A study of chronically
      infected (CI) patients, who represent potential HIV-1 transmitters, was carried
      out in order to ascertain biological factors associated with this trend change.
      DESIGN AND METHODS: Retrospective analysis of CI patients was performed for the
      period 1996-2003. Changes in mean viral load and DR prevalence were assessed in
      CI patients (n = 2328) and compared to those in RI patients (n = 180) living in
      the same geographic area. RESULTS: A decrease was observed in the prevalence of
      DR among RI patients, from 13.0% in 1997-2000 to 4.0% in 2001-2003 (P = 0.04).
      From 1996 to 2000, the mean viral load in the CI patients decreased by 1.34
      log10, to remain steady thereafter. The proportion of CI patients who interrupt
      treatment increased steadily over 1997-2003 from 3.1% to 16.5% (P < 0.0001).
      Since 1999, when genotyping analysis became available, we have observed a 0.9
      log10 decrease in mean viral load among 602 genotyped CI patients harbouring any
      major mutations. CONCLUSION: The decrease in transmission of DR documented in
      Montreal since 2000 coincides with the drop in mean viral load observed in CI
      patients. Factors that contribute to the decrease in viral load include routine
      access to genotyping and availability of more potent antiretroviral drugs. Plasma
      viral load seems to represent the main predictor for the transmission of DR.

PMID- 15577544
TI  - The effect of hepatitis C on progression to AIDS before and after highly active
      antiretroviral therapy.
AB  - OBJECTIVES: To assess the effect of infection with hepatitis C virus (HCV) on the
      progression of human immunodeficiency virus (HIV) disease, before and after the
      introduction of highly active antiretroviral therapy (HAART). METHODS: We used
      data from a multi-centre prospective study of HIV seroconverters. Survival
      analyses were performed to compare the progression to AIDS by HCV serostatus in
      the period before HAART (i.e. June 1991-May 1996) and in the HAART era (i.e. June
      1996-June 2001), controlling for duration of HIV infection. RESULTS: Among the
      1052 persons enrolled, 595 (56.6%) were co-infected; the median follow-up time
      was 9.7 years. Adjusting for demographic variables (age at HIV seroconversion and
      gender), HCV infection had no effect on the progression to AIDS in the pre-HAART
      era [relative hazard (RH) = 0.84; 95% confidence interval (CI), 0.63-1.11],
      whereas it increased the risk in the HAART era (RH = 1.77; 95% CI, 1.15-2.73). In
      the HAART era, the proportion of person-time spent on HAART out of the total time
      at risk was significantly lower among co-infected persons (30 versus 40% for non
      co-infected persons; P-value = 0.001); no significant difference was found for
      dual-therapy (29 versus 25%, respectively; P-value = 0.205); a significant
      difference was found for mono-therapy (15 versus 8%, respectively; P-value <
      0.001). CONCLUSIONS: HCV infection was not a determinant of HIV disease
      progression in the pre-HAART era, whereas since the introduction of HAART, co
      infected individuals seem to have had a faster disease progression. This may in
      part be explained by differences in person-time spent on different antiretroviral
      regimens.

PMID- 15577545
TI  - Infection with concurrent multiple hepatitis C virus genotypes is associated with
      faster HIV disease progression.
AB  - OBJECTIVE: To elucidate the importance of hepatitis C Virus (HCV) genotype in HIV
      disease progression. DESIGN: This study was conducted among 126 HIV/HCV co
      infected drug users with a known interval of HIV seroconversion whose HCV
      genotype was known early in HIV infection. Both clinical progression (to AIDS)
      and immunological progression (to a CD4+ T-cell count of 200 x 10(6) cells/l) by
      HCV genotype were studied using Cox proportional hazards analysis. RESULTS: The
      median duration of follow-up was 7.3 years [interquartile range (IQR), 4.6-10.1
      years]. The majority of the HCV infections concerned genotype 1 and genotype 3;
      The distribution was: HCV type 1: 48%, HCV type 3: 34%, HCV type 4: 13%, multiple
      HCV types: 5%. Concurrent multiple infections consisted of HCV genotypes 1b+3a,
      1b+4 and 3a+4. HCV genotype 1 and multiple HCV genotype infections were
      associated with faster immunological progression [hazard ratio (HR), 2.02; 95%
      confidence interval (CI), 1.04-3.92 and HR, 2.74; 95% CI, 0.95-7.90,
      respectively]. Multiple HCV genotype infection was also associated with faster
      clinical progression (HR, 3.36; 95% CI, 0.82-13.79). These hazard ratios
      increased further and were all significant when analyses were limited to data in
      the pre-HAART era (HR, 3.92; 95% CI, 1.51-10.20; HR, 4.38; 95% CI, 1.04-18.40 and
      HR, 6.54; 95% CI, 1.39-30.76, respectively). CONCLUSION: HIV disease progression
      differs by HCV genotype and is especially faster in individuals whose HCV
      infection involves more than one HCV genotype. The effect of HCV genotype on HIV
      progression was greater in the pre-highly active antiretroviral therapy (HAART)
      era, suggesting that the effectiveness of HAART may diminish the effect of HCV
      genotype on HIV disease progression.

PMID- 15577546
TI  - Successful therapy of hepatitis B with tenofovir in HIV-infected patients failing
      previous adefovir and lamivudine treatment.
AB  - Three HIV-infected patients with chronic hepatitis B (genotype A) were switched
      to adefovir therapy after unsuccessful lamivudine treatment. Surprisingly,
      adefovir therapy failed, although none of the virus isolates displayed mutations
      known to be associated with adefovir resistance (A181V, N236T). In two isolates
      we identified hepatitis B virus DNA polymerase mutation L217R, in one case we
      found multiple frameshifts in the same region. In all cases adefovir was replaced
      by tenofovir, resulting in a significant drop in the viral load.

PMID- 15577547
TI  - Predicted genotypic resistance to the novel entry inhibitor, BMS-378806, among
      HIV-1 isolates of subtypes A to G.
AB  - BMS-378806 targets virus entry by inhibiting the binding of HIV-1 gp120 to the
      CD4 receptor. Env sequences (n = 1226) of subtypes A-G were analysed to determine
      the frequency of mutations associated with resistance to BMS-378806. In line with
      reported sensitivity data, background genotypic resistance to BMS-378806 among
      non-B HIV-1 viruses was found to be higher than in subtype B. These data suggest
      that BMS-378806 may have reduced efficacy against non-B viruses.

PMID- 15577548
TI  - Viral load and CD4 cell response to protease inhibitor-containing regimens in
      subtype B versus non-B treatment-naive HIV-1 patients.
AB  - We compared the response to protease inhibitor-containing highly active
      antiretroviral therapy in 175 HIV-1 treatment-naive patients harbouring subtype B
      versus non-B. No difference in the proportion of patients with viral loads below
      400 copies/ml was observed at month 24. However, there was a significant
      difference in the median CD4 cell increase at month 24. Whether this is caused by
      viral or immune factors warrants further investigation.

PMID- 15577549
TI  - First-line efavirenz versus lopinavir-ritonavir-based highly active
      antiretroviral therapy for naive patients.
AB  - Ninety-seven consecutive patients started anti-HIV therapy based on efavirenz
      (46) or lopinavir-ritonavir (51) in an observational study. Despite the
      significantly more compromised immunological-clinical baseline conditions of
      patients starting lopinavir-ritonavir, a mean clinical-laboratory follow-up of 17
      months showed a comparable laboratory response and therapy interruption or change
      rate, although the toxicity profile of the two compounds proved significantly
      different. Randomized studies comparing these two recommended first-line
      treatments are warranted, particularly from a pharmacoeconomic viewpoint.

PMID- 15577550
TI  - Causes of death in HIV infection: the key determinant to define the clinical
      response to anti-HIV therapy.
AB  - Studies have shown an increased risk of new AIDS/death among injecting drug users
      (IDU) starting highly active antiretroviral therapy (HAART). Of 3872 patients
      starting HAART in the EuroSIDA study, 819 were IDU (21.2%). During 14 769 person
      years of follow-up, 499 patients progressed to new AIDS/death. Compared with
      homosexual individuals, IDU had an increased incidence of new AIDS/death, but
      only for non-HIV deaths. There is an urgent need to define and standardize causes
      of death in observational studies.

PMID- 15577551
TI  - Increased risk of adverse pregnancy outcomes in HIV-infected women treated with
      highly active antiretroviral therapy in Europe.
AB  - Highly active antiretroviral therapy (HAART) may be associated with adverse
      pregnancy outcomes. Among 4372 live births in the European Collaborative Study,
      the prematurity rate increased to 24.9% in 2000-2004. Antenatal HAART use
      initiated pre-pregnancy was strongly associated with prematurity (AOR 2.05, 95%
      CI 1.43, 2.95), particularly severe prematurity. The implication of increased
      prematurity is evidenced in high neonatal mortality in these groups (0.66% for
      infants at 34-36 weeks and 7.37% at < 34 weeks' gestation).

PMID- 15577552
TI  - Changes in HIV prevalence among young Thai men as defined by hepatitis C co
      infection as a marker for mode of transmission.
AB  - To obtain a better understanding of the evolving HIV-1 epidemic in Thailand, we
      utilized antibody to hepatitis C virus (HCV) to indicate the mode of HIV-1
      transmission. Although the proportion of men with HCV co-infection increased
      between 1995 and 2000, the prevalence was similar, whereas the prevalence of men
      not co- infected decreased (1.93-0.46%). This suggests that HIV-1 infection
      associated with parenteral transmission has been stable despite a dramatic
      reduction in the sexual transmission of HIV-1.

PMID- 15577553
TI  - GB virus C and survival in HIV-positive people.

PMID- 15577554
TI  - Response to 'GB virus C during the natural course of HIV-1 infection: viremia at
      diagnosis does not predict mortality' by Bjorkman et al.

PMID- 15577556
TI  - A 7-year longitudinal analysis of IL-2 in patients treated with highly active
      antiretroviral therapy.

PMID- 15577557
TI  - Cerebellopontine degeneration as an immune restoration disease in HIV infection.

PMID- 15577558
TI  - Eosinophilic folliculitis: an example of 'immune reconstitution folliculitis'?

PMID- 15577561
TI  - Diagnostic imaging of retinal disease.

PMID- 15577562
TI  - The epidemiology of age-related macular degeneration.

PMID- 15577563
TI  - Innovative treatments for exudative age-related macular degeneration.

PMID- 15577564
TI  - Diabetic macular edema: a review of past, present, and future therapies.

PMID- 15577565
TI  - Proliferative diabetic retinopathy.

PMID- 15577566
TI  - Controversy in the management of retinal venous occlusive disease.

PMID- 15577567
TI  - Controversies in the management of primary retinal detachments.

PMID- 15577568
TI  - Current management of endophthalmitis.

PMID- 15577569
TI  - The bionic eye: retinal prostheses.

PMID- 15577570
TI  - Value-based medicine: a new paradigm to evaluate treatments for vitreoretinal
      diseases and other medical interventions.

PMID- 15577573
TI  - Identifying risk factors for severe respiratory syncytial virus among infants
      born after 33 through 35 completed weeks of gestation: different methodologies
      yield consistent findings.
AB  - BACKGROUND: Prematurity is a proven risk factor for severe respiratory syncytial
      virus (RSV) infection. Prematurity leads to an increased need for, and duration
      of, hospital admission, intensive care, mechanical ventilation and supplemental
      oxygen, as well as increased mortality. METHODS: The Pediatric Investigators
      Collaborative Network on Infections in Canada (PICNIC) study was a prospective,
      multicenter, cohort study conducted in 16 regions across Canada during 2
      successive RSV seasons: November 2000-June 2001, and November 2001-June 2002. The
      study regions were defined to capture all births and all hospital admissions. The
      FLIP [identify those risk Factors that most Likely may lead to development of RSV
      related respiratory Infection and subsequent hospital admission among Premature
      infants born 33-35 weeks gestational age (GA)] study was a prospective, case
      control study comparison of premature infants hospitalized for RSV infection and
      infants who had not been hospitalized to identify the risk factors that most
      likely would lead to development of RSV infection and subsequent hospital
      admission in this population. RESULTS: The overall hospitalization rate for RSV
      in the PICNIC study was 3.6% for infants of 33-35 weeks GA. In the FLIP study,
      the severity of RSV infection in the 33- to 35-week GA infants was similar to
      that in the younger infants of <33-week GA studied previously by the Infeccion
      Respiratoria Infantil por Virus Respiratorio Sincitial Study Group. Similar risk
      factors were noted in both studies. CONCLUSIONS: RSV is a major cause of
      hospitalization in preterm infants. There is great variability among hospital
      admission rates globally, despite the commonality of severe RSV in many
      countries. Furthermore there are numerous independent risk factors for severe
      RSV, including socioeconomic and environmental factors, that merit further
      investigation. There is likely an additive effect when multiple risk factors are
      present. More research is needed on the various risk factors and their
      significance.

PMID- 15577574
TI  - The changing epidemiology of respiratory syncytial virus and influenza: impetus
      for new control measures.
AB  - BACKGROUND: Influenza and respiratory syncytial virus (RSV) are the most
      important causes of medically attended acute respiratory illnesses. Medical
      encounters for acute respiratory illness peak each winter, coinciding with the
      peak of influenza activity. RSV is the most important cause of hospitalization of
      infants for acute lower respiratory illness. METHODS: Surveillance of influenza
      and RSV have been maintained in Houston since 1974. Hospitalization rates during
      that period were compared with national data. U.S. influenza mortality rates and
      population dynamics were reviewed. RESULTS: The number of deaths attributed to
      influenza in the United States have increased from approximately 15,000 per year
      for the period from 1972 through 1984 to >50,000 from 1990 to 1999. RSV
      hospitalization rates for infants have more than doubled during the same period.
      Influenza epidemics have tended to occur earlier in Texas, with epidemic disease
      evident in early November in 3 of the last 4 years. CONCLUSIONS: Population
      dynamics with increased population density and urbanization probably are
      responsible for worsening of epidemics of the major respiratory viruses. New
      approaches to control will be necessary to reduce impact of these infections.
      These include earlier availability of influenza vaccine each autumn and use of
      antivirals and new vaccines for RSV.

PMID- 15577575
TI  - Severe acute respiratory syndrome coronavirus pathogenesis, disease and vaccines:
      an update.
AB  - BACKGROUND: A novel coronavirus has recently been identified as the cause of
      severe acute respiratory syndrome (SARS-CoV). The ability of this family of
      positive strand RNA viruses to move between species and cause severe disease in
      humans, with the potential for pandemic spread, has been confirmed. METHODS: An
      understanding of the disease and its pathogenesis and the genetics of coronavirus
      infections, as well as strategies to treat or prevent coronavirus infections, are
      essential. The history of coronavirus vaccines and the occurrence of laboratory
      associated SARS-CoV infections underscore the need for stably attenuated strains
      of SARS-CoV and other coronaviruses. RESULTS: Rapid progress has been made in
      understanding the clinical disease of SARS in adults and children. In adults,
      systemic infection with clinical and biochemical abnormalities, as well as
      respiratory infection, may be the rule. SARS is much milder in children younger
      than 12 years old than it is in adolescents and adults. In children age 12 years
      and younger, symptoms are generally nonspecific and cold-like. Numerous
      approaches to the development of SARS-CoV vaccines have been undertaken, and
      there is evidence that antibodies to the spike protein may be protective from
      replication and pathology in animal models. CONCLUSIONS: The availability of
      reverse genetic systems has made it possible to engineer and recover coronavirus
      variants that contain multiple genetically stable mutations that grow well in
      culture but are attenuated for replication, virulence or both. Such variants will
      be platforms for the safe growth of SARS-CoV and candidates for live attenuated
      vaccines.

PMID- 15577572
TI  - Epidemiology of respiratory infections in young children: insights from the new
      vaccine surveillance network.
AB  - BACKGROUND: The New Vaccine Surveillance Network, funded by the Centers for
      Disease Control and Prevention, was established to provide longitudinal data to
      help measure the impact of vaccines that decrease the burden of acute respiratory
      illness in children younger than 5 years of age. Currently 140,000 children
      younger than 5 years of age, nearly 1% of the U.S. population, are under
      surveillance in 3 urban counties, which include Nashville, TN, Rochester, NY, and
      Cincinnati, OH. Prospective, active, population-based surveillance of children
      hospitalized with respiratory symptoms or fever began in 2000, and outpatient
      surveillance began in 2002 in selected winter months. RESULTS: During the first
      year of surveillance, the admission rate for acute respiratory illness/fever in
      children younger than 5 years of age in the surveillance areas was 180 per 10,000
      children. In 61% of these hospitalizations, a respiratory virus was identified.
      Respiratory syncytial viruses, influenza viruses and parainfluenza viruses were
      identified in 30%, and other respiratory viruses were identified in 36%.
      Approximately one-third of children hospitalized had identified high risk
      conditions, primarily asthma (24%). About one-half of the children hospitalized
      were younger than 6 months of age. Polymerase chain reaction doubled the
      diagnostic yield of culture for respiratory syncytial viruses, influenza and
      parainfluenza virus combined. Preliminary data on influenza admissions during the
      4 years indicated considerable variation in admission rates by season and site.
      Annually the mean admission rates during the study period were 43 per 10,000
      children younger than 6 months of age, 9 per 10,000 children 6-23 months of age
      and 4 per 10,000 children 24-59 months of age. CONCLUSION: These data provide
      ongoing surveillance of hospitalizations and other medically attended visits for
      respiratory viral illness in children younger than 5 years of age. Evaluation of
      influenza vaccine effectiveness, the epidemiology of respiratory viruses in
      children and the impact of the pediatric influenza vaccination program are in
      progress.

PMID- 15577577
TI  - Viral respiratory infections in children with technology dependence and
      neuromuscular disorders.
AB  - BACKGROUND: Viral acute respiratory infections represent a significant cause of
      morbidity and mortality across all ages, especially in patients with chronic
      underlying conditions. Although recognized anecdotally, the risks of viral
      infection to those children with chronic underlying conditions rendering them
      technology dependent, or to those children with neuromuscular disorders, have not
      been well studied. METHODS: Studies of children with underlying conditions that
      result in technology dependence and those with neuromuscular disorders who
      required hospitalization for respiratory syncytial virus infection are reviewed.
      Additionally surveys of physician perceptions toward risk factors for severe
      viral illness and prevention in this population of patients are reported.
      Possible mechanisms to explain the increased risk of disease severity with viral
      respiratory infections are explored as well. RESULTS: Current or recent use of
      supplemental oxygen is associated with more severe disease in children with
      chronic underlying conditions, especially bronchopulmonary dysplasia.
      Supplemental oxygen use may be a marker for several factors known to increase the
      severity of viral respiratory illnesses. Children with neuromuscular weakness are
      also likely to experience more severe disease, most likely resulting from
      compromised airway clearance. CONCLUSIONS: Although the number of children who
      are technology-dependent or have severe neuromuscular weakness is small, their
      risk of severe disease after viral respiratory infection may be similar to that
      of premature infants or other high risk groups. A better understanding of the
      factors responsible for severe viral disease in these children would help create
      better strategies for treatment and prevention.

PMID- 15577576
TI  - Human metapneumovirus as a major cause of human respiratory tract disease.
AB  - BACKGROUND: Human metapneumovirus (hMPV) is a newly identified paramyxovirus that
      appears to be one of the most significant and common viral infections in humans.
      The virus, first isolated in 2001, is a clear cause of lower respiratory tract
      disease in both the very young and the frail elderly. The virus causes acute
      wheezing in children or, less commonly, croup or pneumonia. METHODS/RESULTS:
      Molecular epidemiology studies have shown that field strains exhibit sufficient
      sequence diversity to designate 2 subgroups of circulating viruses. Small animal
      and nonhuman primate models of infection have been described, which will allow
      studies of pathogenesis and immunity. Recombinant viruses have already been
      generated by several groups using reverse genetics, which facilitates the study
      of the biology of the virus and the generation of live attenuated vaccine
      candidates. CONCLUSIONS: Ongoing research promises to elucidate the molecular
      basis for pathogenesis and immunity of human metapneumovirus infections and to
      pave the way for rapid vaccine development.

PMID- 15577578
TI  - Animal models for studying respiratory syncytial virus infection and its long
      term effects on lung function.
AB  - BACKGROUND: Human respiratory syncytial virus (hRSV) infection causes a spectrum
      of illnesses ranging from mild infection to life-threatening bronchiolitis and
      respiratory failure. Human studies on the pathogenesis of RSV infection are
      invaluable, but animal models permit advances with the use of experimental
      strategies that would be inappropriate in human studies. METHODS: We review the
      advantages and disadvantages of various animal models for the study of hRSV
      infection. RESULTS: No animal model of hRSV infection replicates the complete
      spectrum of disease severity seen in humans. Available models differ in their
      ability to incorporate genetic technology and to allow the study of immunity,
      vaccine efficacy and treatment interventions. Although hRSV establishes disease
      in primates, this advantage is outweighed by the impracticalities and cost of
      using such models. The study of bovine RSV infection in calves is appealing
      because of parallels with human disease. Among rodent models, BALB/c mice have
      helped delineate the mechanisms underlying vaccine-enhanced RSV disease, and
      cotton rats have been used for preclinical testing. The single major disadvantage
      of studying hRSV in rodent models is the limited extent to which this host
      restricted human pneumovirus replicates in mouse lung tissue. The rodent-specific
      Pneumovirus pathogen, pneumonia virus of mice, causes an infection that mirrors
      severe bronchiolitis and pneumonia in infants infected with RSV, including robust
      virus replication with profound inflammation. CONCLUSION: The recent development
      of the pneumonia virus of mice model has permitted exploration of the mechanisms
      of severe Pneumovirus disease in vivo with the use of sophisticated genetic tools
      and genetically manipulated mouse strains.

PMID- 15577579
TI  - "Hit-and-run" effects of paramyxoviruses as a basis for chronic respiratory
      disease.
AB  - BACKGROUND: The traditional scheme for asthma pathogenesis depends on increased T
      helper type 2 (Th2) over T helper type 1 (Th1) responses to allergic and
      nonallergic stimuli and consequent airway inflammation, hyperreactivity and
      hypersecretion. Here we question whether the innate immune system, including
      airway epithelial cells, and the adaptive one may manifest an aberrant antiviral
      response as an additional basis for chronic inflammatory diseases, including
      asthma. METHODS: We focused on the signal transduction and genetic basis for
      mucosal immunity, inflammation and remodeling, especially in relation to airway
      diseases. We concentrated on the response to paramyxoviruses because these agents
      are closely associated with common acute and chronic airway diseases. We used
      viral, cellular and mouse models, as well as human subjects, for study and made
      comparisons among these systems. Our approach aims to answer 2 major questions:
      (1) what are the factors that control acute paramyxoviral infection; and (2) how
      can these transient infections cause long term airway disease? CONCLUSIONS: Our
      studies show that antiviral defense depends on a special network of epithelial
      immune response genes that signal to the adaptive immune system. Viruses
      ordinarily trigger this network, but it is also permanently activated in asthma,
      even in the absence of viral infection. In addition, we find that, in susceptible
      genetic backgrounds, respiratory viruses cause a "hit-and-run" phenomenon
      indicated by the development of an asthmatic phenotype long after the infection
      has cleared. On the basis of this information, we developed a new scheme for
      asthma pathogenesis that includes epithelial, viral and allergic components and
      allows viral reprogramming of host behavior.

PMID- 15577580
TI  - Novel techniques for assessing infant and pediatric lung function and structure.
AB  - BACKGROUND: Voluntarily performed pulmonary function tests are used in adults and
      older children to assess lung dysfunction and changes in function that occur
      during disease progression and treatment. However, because infants are unable to
      comply with voluntary respiratory maneuvers, alternate testing methods are needed
      to allow similar progress in the treatment and prevention of respiratory
      disorders that begin in infancy. METHODS: Two new methods for assessing lung
      function and structure in infants and young children who are unable to perform
      voluntary respiratory maneuvers are described: raised volume rapid
      thoracoabdominal compression pulmonary function testing and controlled
      ventilation, high resolution computed tomography for lung imaging. CONCLUSIONS:
      Both methods are performed in sedated, sleeping infants and depend on the
      induction of a pause in normal respiratory effort. This pause is produced by
      delivering several deep breaths via the child's nose and mouth using a facemask.
      The induced pause in respiration permits the performance of the respiratory
      maneuvers needed to acquire pulmonary function and high resolution computed
      tomography results in infants. These results are virtually identical with those
      obtainable during voluntary maneuvers performed by adults and older children.
      Together these 2 new methods permit evaluation of the functional and structural
      changes that occur in the lungs and airways of infants and young children with
      respiratory disease. These 2 novel techniques permit the investigation of lung
      disorders as they first develop early in life, thus optimizing opportunities for
      early intervention and prevention.

PMID- 15577582
TI  - Pandemic influenza: is an antiviral response realistic?
AB  - BACKGROUND: Antiviral agents could play a significant role in the response to a
      future influenza pandemic, especially if an effective vaccine is unavailable.
      There is, however, a limited availability of antiviral drugs, as was the case
      during the A/Fujian(H3N2) epidemic in the 2003-2004 season. There are major
      differences among the available antiviral agents in terms of clinical
      pharmacology, adverse effects and resistance profiles, all of which must be
      considered when selecting agents for pandemic use and stockpiling. The logistic
      issues involved in delivering the drug to large populations must also be
      considered. The M2 ion channel inhibitors amantadine and rimantadine are
      partially effective for chemoprophylaxis of pandemic influenza, and when used for
      early treatment they provide some symptom relief. Interpandemic studies
      demonstrate that the neuraminidase inhibitors would be effective for both
      prevention and treatment of influenza. CONCLUSION: Given the limited supply and
      the previously demonstrated inability of the manufacturing sector to meet surging
      needs, an effective antiviral response could not currently be launched in the
      United States. Antiviral agents could be important in managing and treating
      pandemic influenza and reduce lower respiratory complications and
      hospitalizations.

PMID- 15577581
TI  - Immunization against viral respiratory disease: a review.
AB  - BACKGROUND: Healthy and at risk children are susceptible to the morbidity and
      mortality associated with viral-induced respiratory diseases, including
      respiratory syncytial virus (RSV) and influenza. The World Health Organization is
      attempting to develop and distribute effective vaccines to prevent/reduce key
      viral respiratory diseases. METHODS: The goals of a vaccination program for viral
      respiratory infections include the prevention of lower respiratory tract
      infections and prevention of infection-associated morbidities, hospitalization
      and mortality. This article explores influenza and RSV vaccine developments.
      RESULTS: There are 2 influenza vaccines, trivalent inactivated and live, cold
      adapted, attenuated. Trivalent inactivated vaccine is indicated for persons older
      than 6 months of age. Currently <10%, <30% and <30% of healthy children, healthy
      adults and high risk children, respectively, are vaccinated. Efficacy is from 70
      to 90% in healthy adults younger than 65 years of age and 30-90% in children,
      with lower efficacy in younger children. Live, cold-adapted, attenuated vaccine
      is indicated for healthy persons 5-49 years of age and usually is 70-90%
      effective. Various RSV vaccine formulations are being investigated. The Advisory
      Committee on Immunization Practices (ACIP) recommends influenza vaccination for
      children 6-23 months old. Studies support immunization of all children, not only
      those at high risk. Current ACIP recommendations focus on high risk persons and
      do not include school age children. A universal immunization program for all
      children could benefit the entire community. CONCLUSION: Effective vaccines are
      available for some viral respiratory pathogens (eg, influenza virus), but not for
      most mucosally restricted respiratory viral pathogens. Research should continue
      into safe and effective vaccines for all childhood viral illnesses.

PMID- 15577583
TI  - Thyroid blocking policy--revisited.

PMID- 15577584
TI  - Efficacy of low and high 131I doses for thyroid remnant ablation in patients with
      differentiated thyroid carcinoma based on post-operative cervical uptake.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy of low (1110 MBq
      (30 mCi)) and high (3700 MBq (100 mCi)) 131I doses on the ablation of post
      surgical remnants in patients with thyroid cancer based on the measurement of
      post-operative cervical uptake. METHODS: The study was conducted on 155 patients
      without metastases after thyroidectomy who received a 1110 or 3700 MBq ablative
      dose and who were assessed by pre-therapy cervical uptake. The patients were
      divided into six groups according to the uptake result and the dose received.
      Successful therapy was defined as a negative scan 6 months to 1 year after
      ablation. RESULTS: Ablative therapy was successful in 90% of patients with uptake
      <2% who received the 1110 MBq dose (n=30) and in 92.5% of patients who received
      the 3700 MBq dose (n=40), P=0.95. In the group with uptakes ranging from 2% to
      5%, successful therapy was observed in 65% of patients receiving 1110 MBq (n=20)
      and in 86.6% of patients receiving 3700 MBq (n=30), P=0.14. In patients with
      uptake >5%, a 46.6% success rate was obtained for the 1110 MBq dose (n=15), while
      efficacy was 70% in patients receiving 3700 MBq (n=20), P=0.16. CONCLUSION: This
      study demonstrated the efficacy of low doses in patients with lower remnants
      after surgery (uptake <2%), the inverse correlation between uptake and ablation
      efficacy with low and high doses, and the usefulness of the measurement of
      cervical uptake for the definition of the ablative 131I dose.

PMID- 15577586
TI  - Optimization of parathyroid imaging by simultaneous dual energy planar and single
      photon emission tomography.
AB  - BACKGROUND: Single photon emission tomography (SPET) gives valuable 3-dimensional
      information, but prolongs the time of imaging and increases the possibility of
      patient movement. We therefore investigated a method for the optimization of
      SPET. METHOD: Using an in-house fabricated thyroid/parathyroid neck phantom
      simultaneous dual energy (DE) 1223I/99mTc imaging to localize parathyroid glands
      was assessed both in planar and SPET modes. RESULTS: Experiments demonstrated
      improved spatial resolution and contrast for planar pinhole imaging compared to
      parallel collimation. For DE-SPET compared to planar pinhole imaging more glands
      in the phantom were visualized by the improved contrast. CONCLUSION: We conclude
      that DE-SPET for parathyroid imaging is feasible to aid the accurate localization
      of parathyroid adenomas. For planar imaging pinhole collimation is superior to
      parallel hole collimation.

PMID- 15577585
TI  - Effect of radioiodine therapy on thyroid nodule size and function in patients
      with toxic adenomas.
AB  - BACKGROUND: Autonomously functioning toxic adenomas are a common cause of
      hyperthyroidism. Although 131I seems to be a good therapeutic option with little
      postablative hypothyroidism for these patients, only a small number of recent
      studies have objectively evaluated changes in nodule size by ultrasonography
      following radioiodine therapy. METHODS: We prospectively followed 39 patients
      with a mean age of 51.2 (35-75) years for 12 months and the patients who remained
      toxic thereafter, until euthyroidism was provided. Thyroid function tests,
      sonographic volumes were determined initially and 3, 6 and 12 months after
      treatment. Radioiodine doses of 3.7 MBq.g(-1) thyroid tissue corrected to a 100%
      24 h 131I uptake were given. Thirty patients received a single dose, two required
      two doses and three required three to five doses of 131I due to persistent
      thyrotoxicosis. Sonographic volumes of the diffuse parts of the glands decreased
      significantly by 18% from a mean+/-SD value of 50+/-27.6 ml to 41+/-27.4 ml by
      the end of the 12 months. A significant decrease (8.3%, P=0.002) was achieved in
      the first three months. Toxic adenomas decreased in size more efficiently (54%)
      from a mean of 26+/-24 ml to 12+/-10 ml during 12 months, but also most
      significantly (28.8%, P=0.003) in the first 3 months of the follow-up. Thirty of
      the patients (76.9%) became euthyroid at the end of 12 months of follow-up. Four
      patients (10.3%) became overtly hypothyroid during the follow-up. CONCLUSION:
      Single or multiple doses of radioiodine can successfully treat toxic adenomas
      with a low rate of hypothyroidism and considerable nodule-volume reduction.

PMID- 15577588
TI  - Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips
      ADAC CPET PET scanner.
AB  - INTRODUCTION: Fully three-dimensional (3-D) reconstruction algorithms have the
      potential to better utilize PET data acquired in true 3-D acquisition modes, as
      compared to 2-D approaches involving data reduction through rebinning procedures
      followed by a 2-D or 2.5-D reconstruction. Our previous studies, involving
      simulated and real phantom data from PET scanners working purely in 3-D
      acquisition mode, showed that the fully 3-D reconstruction approaches bring
      appreciable improvement on physical measures and visual image quality as well.
      Reconstruction procedures utilized in those studies were based upon the row
      action maximum likelihood algorithm (RAMLA) implemented on our clinical scanners.
      The purpose of this study was to investigate if the fully 3-D RAMLA
      reconstruction software brings an appreciable improvement in clinical image
      quality and reader confidence. MATERIALS AND METHODS: Ninety patient scans
      acquired on the Philips CPET scanner at our institution were reconstructed using
      2.5-D RAMLA and 3-D RAMLA with differing reconstruction parameters. These scans
      were blindly presented to four experienced PET scan readers who graded various
      aspects of image quality. RESULTS: Our study concluded that 3-D RAMLA on the CPET
      scanner reduces artifacts and image noise and improves clinical confidence in
      interpreting PET images. CONCLUSION: This study led to the routine use of 3-D
      RAMLA reconstruction on the CPET scanner at our institution.

PMID- 15577587
TI  - Validation of quantitative accuracy of the post-injection transmission-based and
      transmissionless attenuation correction techniques in neurological FDG-PET.
AB  - BACKGROUND: We evaluated the quantitative accuracy of the post-injection
      transmission-based segmented attenuation correction (SAC) technique and
      transmissionless calculated attenuation correction (CAC) technique in both 2D and
      3D scanning for the brain, and compared the results with those obtained using the
      pre-injection transmission-based measured attenuation correction (MAC) technique,
      which is generally accepted as the 'gold standard'. METHODS: We examined
      [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on both a
      cylindrical phantom and in 10 patients with epilepsy. The statistical analyses
      were performed using both the region of interest (ROI) method and statistical
      parametric mapping (SPM). RESULTS: In the ROI analysis, [18F] activity
      concentration values obtained by the SAC technique were well correlated with
      those obtained by the MAC technique (2D, R2=0.94; 3D, R2=0.98; P<0.001), although
      these values were underestimated over the entire brain. The CAC technique was
      also found to have significant correlation with the MAC technique (2D, R2=0.84;
      3D, R2=0.86; P<0.001), but this technique showed apparent overestimation or
      underestimation in several parts of the brain. In the SPM analysis, there were no
      significant differences between the SAC and MAC technique, while those values
      obtained by the CAC technique were significantly lower in the parieto-occipital
      region and higher in the lower frontal region (P<0.001, uncorrected). CONCLUSION:
      The SAC technique was superior to the CAC technique in both 2D and 3D scanning,
      although we found that both the SAC and CAC techniques had some problems in
      quantitative evaluation. We considered that the SAC technique may yield adequate
      qualitative measurements of the [18F] activity concentration value after global
      normalization.

PMID- 15577589
TI  - Physiological uptake of [18F]fluorodeoxyglucose in the neck and upper chest
      region: are there predictive characteristics?
AB  - OBJECTIVE: The purpose of this study was to assess (patient) characteristics that
      might influence the prevalence of physiological uptake of [18F]fluorodeoxyglucose
      (FDG) in the neck and upper chest region (FDG NUC) in positron emission
      tomography (PET) imaging. METHODS: Retrospective study of static FDG PET scans in
      patients with malignant lymphoma, head and neck, lung or thyroid malignancy. The
      investigated determinants were gender, age, body mass index (BMI), tumour type,
      referring centre (community or university hospital), first or later PET scan, and
      use of benzodiazepines. RESULTS: Eighty (31%) of 260 scans showed FDG NUC. We
      found a strong inverse relation between age and FDG NUC (P<0.001). After
      adjusting for age, older head and neck tumour patients were more at risk for
      developing FDG NUC compared with other tumours (P=0.011). Gender, use of
      benzodiazepines, referring specialist, first or later PET scan or low BMI (<20
      kg.m(-2)) did not influence the prevalence of FDG NUC. CONCLUSION: Multivariate
      logistic regression showed a strong inverse association between age and FDG NUC.
      No association between low BMI and FNUC could be established. In our hospital no
      protective effect of benzodiazepines could be determined. These data suggest that
      a trial designed to evaluate the efficiency of interventions to diminish FDG NUC
      should focus on younger patients.

PMID- 15577590
TI  - Initial observations of 99mTc labelled locked nucleic acids for antisense
      targeting.
AB  - BACKGROUND AND OBJECTIVE: The most recent DNA analogues to become commercially
      available are known as locked nucleic acids (LNAs). The aim of this study was to
      evaluate the properties of LNAs for antisense targeting. METHODS: A 15 mer LNA
      antisense to RIalpha mRNA was studied in cell culture. The antisense LNA (5'
      amine linker-TGCCTCCTCACTGGC) was purchased along with its sense control LNA.
      Surface plasmon resonance was used to compare affinity constants with uniform 18
      mer phosphorothioate (PS) DNA and uniform 18 mer phosphodiamidate morpholinos
      (MORFs, another DNA analogue). After radiolabelling with 99mTc via MAG3, the
      antisense and sense LNAs were added at 5 nM to wells containing ACHN cells in
      culture and accumulations measured over 24 h. Subcellular partition was
      determined after 16 h of incubation by separating membrane bound, cytoplasmic and
      nuclear fractions. The cell studies were conducted both with naked LNAs and with
      liposomes (oligofectamine) as carrier. RESULTS: Radiochemical purity was about
      95% after purification on a P4 column and each LNA was radiolabelled at about 20
      GBq.micromol(-1) (100.microCi.microg(-1)). The surface plasmon resonance results
      showed a more favourable dissociation constant for the duplex with DNA of the 15
      mer LNA (0.55 x 10(-10).M(-1)) compared to the duplex with 18 mer DNA and 18 mer
      MORFS (2.05 and 1.06 x 10(-10).M(-1), respectively). Because of lower
      dissociation constants, the hybridization affinities of LNAs are therefore higher
      than those of uniform and identical PS DNAs or MORFs. The cellular accumulations
      suggested an antisense effect in that the antisense LNA accumulation was higher
      than sense both when added naked (1.8% vs. 0.4% at 24 h) and with liposome
      carrier (3.8% vs. 1.0% at 24 h). Thus while absolute cellular uptake was lower
      than that observed by this laboratory with other oligomers, the antisense/sense
      differential was higher. The number of antisense LNAs accumulating per cell
      specifically (i.e., antisense minus sense) was about 45,000 naked and about
      100,000 with carrier. Subcellular partition showed that both LNAs were
      partitioned to each fraction with antisense accumulations greater than sense and
      carrier accumulations greater than naked as before. That as much as 2.9% of the
      antisense LNA (with carrier) was in the cytoplasmic or nuclear factions
      demonstrates that the LNA was internalized. CONCLUSIONS: LNAs appear to be
      attractive oligomers for antisense targeting and other radiopharmaceutical
      applications.

PMID- 15577591
TI  - Analysis of technical and clinical variables affecting sentinel node localization
      in patients with breast cancer after a single intradermal injection of 99mTc
      nanocolloidal albumin.
AB  - AIM: To investigate the technical, clinical and pathological findings that can,
      potentially, affect pre-operative lymphoscintigraphy in visualizing sentinel
      lymph node (SLN) and intra-operative probe detection of SLN in patients with
      breast cancer. METHODS: One hundred and forty-two consecutive female patients
      with, clinically, a solitary, small breast cancer and clinically N0 axilla were
      enrolled. Preoperative lymphoscintigraphy was performed by a single intradermal
      injection of 99mTc nacolloidal albumin (Nanocoll) the day before surgery. For
      radioguided surgery two gamma probes with diameters of 11 mm and 15 mm, and set
      up with a count rate ranging from 1 to 4 s were used. The following variables
      were evaluated: patient's age, radiotracer dose, volume of injectate, primary
      tumour location, primary tumour size, and presence and extension of axillary
      nodal metastases. RESULTS: Lymphoscintigraphy showed high sensitivity in
      visualizing the SLN (98% success rate) and it resulted in a rapid technique since
      SLN was visualized within 30 min from injection in 85.21% of cases for the whole
      series. The probe detection rate was also very high (97.8% success rate): the
      mean per cent uptake in the SLN was 0.98. Statistical analysis showed that no
      parameter was found to have significantly influenced either SLN visualization at
      lymphoscintigraphy or SLN probe detection at surgery. CONCLUSION: In our
      experience, lymphoscintigraphy performed by a single intradermal injection of
      Nanocoll was an effective and rapid technique for visualizing axilla SLNs in
      breast cancer patients. Moreover, this technique appeared to be independent of
      any technical, clinical and pathological findings.

PMID- 15577592
TI  - Meta-[123I]iodobenzylguanidine is selectively radiotoxic to neuroblastoma cells
      at concentrations that spare cells of haematopoietic lineage.
AB  - BACKGROUND: The Auger electron-emitting agents meta-[125I]iodobenzylguanidine
      (125I-MIBG) and 123I-MIBG have been proposed as alternatives to 131I-MIBG for the
      treatment of neuroblastoma, due to the absence of a cross-fire effect which may
      minimize bone marrow toxicity. However, the differential toxicity of 123I-MIBG
      towards neuroblastoma cells and cells of haematopoietic lineage has not been
      studied. OBJECTIVE: To compare the toxic effects of 123I-MIBG on SK-N-SH and SK-N
      BE(2) neuroblastoma cells and on cells of haematopoietic lineage, specifically HL
      60 human myeloid leukemia cells and bone marrow stem cells (BMSCs) from human
      adult donors. METHODS: The antiproliferative effects of exchange-labelled or no
      carrier added (n.c.a.) 123I-MIBG, unlabelled MIBG or the
      trimethylsilylbenzylguanidine (MTBG) precursor used to prepare n.c.a. 123I-MIBG
      against SK-N-SH or SK-N-BE(2) cells or HL-60 cells were evaluated using a cell
      proliferation assay. The toxicity of 123I-MIBG towards SK-N-SH cells or BMSCs
      from healthy adult human donors was studied using a clonogenic assay. RESULTS:
      123I-MIBG was strongly growth inhibitory to SK-N-SH or SK-N-BE(2) cells at
      concentrations (IC50 185-370 mBq.ml(-1); IC90 740 mBq.ml(-1)) that were sparing
      to HL-60 cells. Treatment of SK-N-SH cells with 74 mBq of 123I-MIBG decreased
      colony formation by >90%, whereas colonies from all three populations of stem
      cells were formed at amounts up to 370 mBq. It was discovered that the MTBG
      precursor was non-specifically toxic towards both SK-N-SH cells and HL-60 cells,
      suggesting the need to purify n.c.a. 123I-MIBG for clinical use. CONCLUSION: Our
      results suggest that 123I-MIBG is a promising novel radiotherapeutic agent for
      neuroblastoma. For the first time, we report that the MTBG precursor used to
      prepare n.c.a. 123I-MIBG was toxic towards neuroblastoma cells as well as to HL
      60 cells, representing cells of the haematopoietic lineage, suggesting the need
      for purification.

PMID- 15577593
TI  - Importance of receptor density in alpha radioimmunotherapy in B cell
      malignancies: an in-vitro study.
AB  - BACKGROUND: External beam radiotherapy and beta radioimmunotherapy (RIT) are
      effective treatments for lymphoid malignancies. The development of RIT with alpha
      emitters is attractive because of the high linear energy transfer (LET) and short
      path length, allowing higher tumour cell kill and lower toxicity to healthy
      tissues. AIM: To assess the binding of rituximab to samples of B cell chronic
      lymphocytic leukaemia (B-CLL) and splenic lymphoma with villous lymphocytes
      (SLVL), and to evaluate the induction of apoptosis by conventional therapies as
      well as with Bi conjugated to rituximab. METHOD: 213Bi was eluted from a 225Ac
      generator and conjugated to CD20 antibody (rituximab) with CHX-A''-DTPA as
      chelator. Binding assays with 213Bi-rituximab were correlated to antibody binding
      capacity obtained by flow cytometry. Apoptosis was scored by flow cytometric
      analyses of the cells stained with annexin V-FITC and 7-amino-actinomycin D.
      RESULTS: Binding of 213Bi-rituximab was significantly lower for B-CLL compared to
      SLVL samples (12+/-3 and 42+/-10 213Bi atoms per cell, respectively, at 370
      kBq.ml(-1)). The induction of apoptosis did not differ significantly between the
      two groups (B-CLL and SLVL) after external gamma irradiation or treatment with
      methylprednisolone and fludarabine (17+/-12% and 18+/-11%; 23+/-14% and 21+/-12%;
      9+/-9% and 11+/-8%, respectively; all results expressed as percentages of all
      cells). Rituximab conjugated or not to 213Bi induced significantly more apoptosis
      in SLVL (42+/-19% and 42+/-17%) compared to B-CLL samples (27+/-12% and 6+/-8%).
      CONCLUSION: Binding assays confirm that SLVL samples present more CD20 antigens
      compared to B-CLL samples. Conventional therapies such as fludarabine,
      methylprednisolone or external gamma irradiation induce similar responses in the
      two populations but SLVL samples present higher sensitivity towards 213Bi
      rituximab. These data are in favour of alpha-RIT in SLVL patients.

PMID- 15577594
TI  - The lung scan and the abnormal chest X-ray: difficult diagnoses.
AB  - PURPOSE: The ventilation-perfusion lung scan is evolving into an alternative
      diagnostic test for patients who cannot tolerate contrast computed tomography
      studies. It is likely that this shift in patient population will result in a
      larger proportion of patients with abnormal chest radiographs. The purpose of
      this study was to determine whether a computer based scan analysis could assist
      clinical interpretation in this diagnostically difficult population. METHODS:
      Radionuclide ventilation-perfusion (V-P) images were obtained from 118 patients
      with normal chest radiographs and 144 patients with abnormal radiographs who
      underwent pulmonary angiography within 3 days of the radionuclide study.
      Artificial neural networks (ANNs) were created using only objective image-derived
      inputs to diagnose the presence of pulmonary embolism. The ANN predictions were
      compared with clinical scan interpretations and with the results of angiography.
      RESULTS: In both patients with normal and with abnormal chest radiographs, the
      ANN based method performed comparably to the clinical interpretation of record.
      An average of the clinical and ANN estimates of the likelihood of embolism was
      more accurate than was either method alone. CONCLUSIONS: Computer-based V-P scan
      analysis performs comparably to clinical interpretation for patients with
      abnormal chest radiographs. The different analytical perspective of the digital
      method improves test performance when used in conjunction with standard clinical
      interpretation. This can improve the chances of reaching a diagnosis for patients
      who lack diagnostic alternatives to the V-P scan.

PMID- 15577595
TI  - Gastric scintigraphy with a liquid-solid radiolabelled meal: performances of
      solid and liquid parameters.
AB  - AIM: To assess the clinical performance of parameters of liquid-solid gastric
      emptying (GE) scintigraphy. METHODS: Fifty-three controls and 476 patients
      underwent GE scintigraphy using a liquid-solid test meal (non-ulcer dyspepsia,
      n=180; gastro-oesophageal reflux disease, n=123; dyspepsia after anti-reflux
      surgery, n=29; diabetes mellitus, n=96; cystic fibrosis prior to heart-lung
      transplantation, n=48). Time-activity curves were fitted by a power exponential
      function and half-emptying times (T1/2) were computed. The lag phase (Tlag) and
      constant emptying (TRE) times of solid emptying were also calculated using a
      mathematical method (maximum slope tangent method). RESULTS: TRE and T1/2 of
      solids were higher in each subgroup of patients vs. controls (P=0.0001) and in
      cystic fibrosis patients vs. gastro-oesophageal reflux patients (P=0.0001). Tlag
      was significantly higher only in non-ulcer dyspepsia patients vs. controls
      (P=0.001). There was no significant difference for liquid parameters. Using the
      mean+/-1.96 SD of the solid and liquid T1/2 values obtained in controls, GE was
      normal (n=251; 53%), delayed (n=183; 38%), accelerated (n=33; 7%) or mixed (n=9;
      2%). Delayed solid T1/2 was the most prominent alteration (n=189), and
      alterations of liquid GE alone were present in only 24 (5%) patients. A good
      correlation was found between solid T1/2 and TRE (r=0.88), but no correlation
      between Tlag and TRE, suggesting that these estimates represent independent
      phases of GE. In 26 patients, all GE parameters of solids and liquids were normal
      except Tlag (n=8) or TRE (n=18). The lack of significant differences between the
      different patient subgroups did not allow emptying profiles to be drawn according
      to patient pathology. CONCLUSION: Liquid GE scintigraphy provided poor and
      unreliable information in terms of patient discrimination and the drawing of
      pathophysiological profiles of abnormal GE. Tlag and TRE may confirm GE
      alteration, especially when solid T1/2 values are at the superior limit of
      normality, and may improve the performance of GE scintigraphy, rather than using
      liquid parameters.

PMID- 15577596
TI  - 16-Detector multislice CT-skeletal scintigraphy image co-registration.
AB  - OBJECTIVE: Co-registration of bone scintigrams with radiographs has been used in
      the diagnosis of wrist injuries, although co-registration of tomographic bone
      scintigraphy with computed tomography (CT) has not been widely reported. We
      describe a co-registration technique in patients with possible wrist fracture.
      METHODS: The technique was used on three patients and involved placing the wrist
      on a Perspex board and tracing the outline of the forearm and hand with a pen to
      try and ensure accurate repositioning on the board for the two sets of imaging.
      Four point source markers were attached to the board during both examinations.
      Single photon emission computed tomography (SPECT) was performed 4 h after
      injection Tc-methylenediphosphonate (MDP), using a dual-headed gamma camera. CT
      images were acquired on a 16-detector CT unit. The SPECT and CT images were co
      registered with commercially available image fusion software. The centre of the
      four markers was identified in both sets of images and a rigid body point match
      algorithm was used. Before patient studies, the technique was tested using a
      phantom. RESULTS: In all the phantom and clinical studies it was possible to
      identify the positions of all the markers. There were varying degrees of success
      in patient repositioning. CONCLUSION: We describe a technique that may aid the
      fusion of functional images from skeletal scintigraphy with the exquisite
      anatomical detail from the latest CT technology, in the detection of occult wrist
      fractures. The technique may aid fracture localization and/or detection and might
      help distinguish the clinically important scaphoid fractures from other benign
      carpal lesions.

PMID- 15577601
TI  - Making sure the treatment of myositis does not get "lost in translation".

PMID- 15577602
TI  - Clinical assessment in adult onset idiopathic inflammatory myopathy.
AB  - PURPOSE OF REVIEW: Outcome measures have been developed and validated for many
      rheumatic diseases and used in clinical trials. The clinical assessment and
      measures of improvement in clinical trials of patients with idiopathic
      inflammatory myopathy (IIM) has varied to date and over the past few years an
      attempt has been made to reach a consensus in defining this improvement. RECENT
      FINDINGS: The IMACS group (International Myositis Outcome Assessment
      Collaborative Study) has proposed core set measures for disease activity and
      damage assessment in adults. Distinguishing between activity and damage can be
      difficult and measures to ascertain this are discussed. SUMMARY: Significant
      progress has been made in developing international consensus in the assessment of
      IIM. Further developments are underway to assess the reliability and validity of
      measures that should capture the multisystem nature of this disease.

PMID- 15577603
TI  - Clinical assessment in juvenile idiopathic inflammatory myopathies and the
      development of disease activity and damage tools.
AB  - PURPOSE OF REVIEW: In the past few years, adult and pediatric experts in the
      field have combined their skills to achieve major advances in clinical research
      on pediatric inflammatory myopathies. As rare diseases, it has become recognized
      that international trials are needed to assess drug treatments and their long
      term sequelae. Tools for assessing specific aspects of disease are available and
      have been studied to better understand their performance strengths and
      limitations. These tools have been incorporated into disease activity and damage
      scores that have been developed by international consensus and are now being
      evaluated. RECENT FINDINGS: This review focuses on the tools whose evaluations
      have been published in the past year and includes methods to assess muscle
      strength and function in children with myositis. Two international collaborative
      efforts have focused on disease activity and damage assessments, and their
      findings are discussed. Some papers highlighting further diagnostic
      investigations are also reviewed. SUMMARY: The standardization of assessment
      tools has enormous implications for future clinical practice: (1) Clinicians who
      are not experienced in these rare disorders will be able to evaluate their
      patients appropriately and highlight important clinical signs that are of
      prognostic importance. (2) International drug trials can be undertaken and thus
      improve our understanding of the impact of medication on the disease process. (3)
      Follow-up studies can be undertaken with sufficient numbers of patients to answer
      questions about the long-term sequelae of the disease and its treatments.

PMID- 15577604
TI  - Use of imaging to assess patients with muscle disease.
AB  - PURPOSE OF REVIEW: A variety of imaging modalities can be used in muscle
      diseases. These range from plain x-rays to conventional magnetic resonance
      imaging (MRI) and phosphate magnetic resonance spectroscopy (MRS). This review
      places these imaging methods into their relevant clinical contexts on the basis
      of the best available research evidence. RECENT FINDINGS: Plain x-rays have
      limited roles in imaging patients with muscle disease. An exception is
      identifying calcinosis in patients with myositis; there is some evidence that
      effective early treatment may reduce its frequency and severity. Scintigraphy has
      been used in several centers but it appears to have limited value. Ultrasound,
      though successfully used in a number of units, is relatively little used, though
      the evidence suggests it would be sensible if this method were adopted more
      widely. MRI is currently the key imaging modality. It is useful in diagnosing
      pyomyositis, diabetic muscle infarction, and inflammatory myositis. Its main
      proven value is identifying the best sites for biopsy in early myositis, though
      it can help differentiate between different forms of muscle disease when there is
      diagnostic uncertainty. The area of most intense ongoing original research is
      MRS, which can show the bioenergetics of normal and abnormal muscles. Changes in
      the ratios of inorganic phosphate and phosphocreatine, particularly during
      exercise provide insights into the metabolic consequences of muscle diseases and
      may, in the future, suggest alternative therapeutic approaches. SUMMARY: Magnetic
      resonance imaging is a useful adjunct when diagnosing muscle diseases. It is
      particularly useful to identify suitable sites for muscle biopsy. Ultrasound may
      be equally helpful, though there is less supporting evidence from existing
      research. MRS is the area in which most current novel research is focused.

PMID- 15577605
TI  - Is it really myositis? A consideration of the differential diagnosis.
AB  - PURPOSE OF REVIEW: The idiopathic inflammatory myopathies are an important and
      treatable group of disorders. However, the potential toxicity associated with the
      immune therapeutic regimens used to treat these disorders may be significant;
      therefore, accurate diagnosis before such treatment is essential. The
      differential diagnosis is potentially large. Accurate diagnosis usually depends
      on a combination of careful clinical assessment in conjunction with detailed
      laboratory investigations. Muscle biopsy remains essential in achieving an
      accurate diagnosis that will then guide treatment. This review describes the
      diagnostic approach used. RECENT FINDINGS: There has been debate over the
      requirements for an accurate diagnosis of inflammatory myopathy (i.e.,
      polymyositis and dermatomyositis). It is increasingly recognized that there can
      be clinical and muscle histopathologic overlap between the features of
      inflammatory myopathies and those of other muscle disorders, in particular, the
      genetic muscular dystrophies. Pathologic findings of inflammation and major
      histocompatibility complex upregulation, although typical of inflammatory
      myopathies, have been shown to occur in some muscular dystrophies, complicating
      the diagnostic process. Inclusion body myositis is much less responsive to
      immunotherapy and is now recognized as the most common acquired muscle disease in
      those older than 50 years of age. It is likely that genetic muscular dystrophies
      and inclusion body myositis account for some cases of apparently "treatment
      resistant" myositis. SUMMARY: A thorough clinical assessment, including a
      detailed family history, complemented by electromyography and creatine kinase
      measurements, should be undertaken in any patient with presumed idiopathic
      inflammatory myopathy. In addition, a muscle biopsy remains essential in all
      cases. A precise tissue diagnosis confirming features of an active inflammatory
      process should be achieved before immunosuppressive treatment is commenced. An
      increasing array of immunocytochemical and histioenzymatic stains now allows a
      full analysis and will help to confirm or exclude virtually all the differential
      diagnostic possibilities considered in this review. Electron microscopy may also
      be valuable in selected cases. Close collaboration between clinicians and muscle
      pathologists is essential in allowing the most accurate interpretation of
      myopathologic findings in the clinical context.

PMID- 15577606
TI  - Myositis specific autoantibodies: changing insights in pathophysiology and
      clinical associations.
AB  - PURPOSE OF REVIEW: Defined autoantibodies are found in about half of the patients
      with myositis. Traditionally, these autoantibodies have been divided into
      myositis specific autoantibodies (MSAs) and myositis associated autoantibodies.
      Several studies have shown that MSAs are associated with specific clinical
      characteristics and can aid our understanding of the pathophysiology of myositis.
      RECENT FINDINGS: Recent studies suggest that some MSAs are markers of specific
      inflammatory muscle diseases (e.g., anti-SRP for an immune-mediated necrotizing
      myopathy) and not just of myositis in general. Furthermore, new insights are
      emerging about the pathophysiology of MSAs, in particular anti-Jo-1. Based on
      these new insights, an alternative hypothesis of the formation of anti-Jo-1
      autoantibodies is presented in which the immune system itself rather than muscle
      is the site of antigen presentation. SUMMARY: The recognition that some MSAs are
      markers of specific disease entities that were once commonly referred to as
      (poly)myositis, aids the development of better disease definitions. The changing
      insights in the function of the Jo-1 antigen and the emergence of new hypotheses
      on the formation of the Jo-1 antibody, open new avenues for future research aimed
      at unraveling the mystery of myositis.

PMID- 15577607
TI  - Myositis: an update on pathogenesis.
AB  - PURPOSE OF REVIEW: The etiology and much about the pathogenesis of the
      inflammatory myopathies remain a mystery. In this review, we investigate recent
      research efforts to understand the pathogenesis of the diverse entities of
      polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM),
      diseases that result from interactions between environmental risk factors and
      genetic susceptibility. RECENT FINDINGS: Over the past year, there has been
      considerable progress toward better understanding of IBM, with relatively few
      developments toward understanding PM and DM. Although these diseases may share
      some common clinical phenotypic and serologic components, they differ on a
      molecular and cellular level. SUMMARY: The need for definitive, safer therapies
      in these diseases makes vital the search for defining detailed pathogenesis of
      inflammation and muscle fiber damage at the molecular level.

PMID- 15577608
TI  - Have recent immunogenetic investigations increased our understanding of disease
      mechanisms in the idiopathic inflammatory myopathies?
AB  - PURPOSE OF REVIEW: The idiopathic inflammatory myopathies (IIM) continue to
      provide a challenge given the variable effectiveness of the available treatments,
      and immunogenetic studies are ongoing to further elucidate IIM disease
      mechanisms. This review examines how recent research has improved our
      understanding of the mechanisms that lead to IIM. RECENT FINDINGS: HLA-DRB1
      studies in a large homogenous cohort of UK Caucasian patients have confirmed that
      polymyositis (PM) and dermatomyositis (DM) are not genetically identical diseases
      while other studies have shown that tumor necrosis factor alpha is genetically
      implicated in disease susceptibility. Some remarkable results from an
      international collaboration, correlating gene-environment interactions, clearly
      suggest that ultraviolet light is capable of modulating both clinical and
      immunologic features of IIMs. Studies on microchimerism are unraveling
      interesting associations in juvenile DM patients, and bolstering the hypothesis
      that myositis may be an 'allo-immune' disease. mRNA gene expression profiling is
      helping to increase our understanding of myositis pathogenesis, whilst animal
      models have provided new information on the roles of Th1 responses and nitric
      oxide synthase in muscle disease. New candidate genes have been examined in
      inclusion body myositis (IBM), and a novel gene transfer experiment has been
      conducted, which led to significant changes in expression of the IBM phenotype.
      SUMMARY: Improving the understanding of the immunogenetics and immunopathogenesis
      of the IIMs may in the future provide novel therapeutic targets, and thus improve
      outcomes in these difficult diseases.

PMID- 15577609
TI  - Illness and art: the legacy of Paul Klee.

PMID- 15577610
TI  - Raynaud phenomenon and the vascular disease in scleroderma.
AB  - PURPOSE OF REVIEW: Raynaud phenomenon is the earliest and most common clinical
      manifestations of scleroderma (systemic sclerosis). Therefore, Raynaud phenomenon
      offers the best window into the investigation of the early steps in the
      pathogenesis of systemic sclerosis. This review focuses on the differential
      diagnosis of Raynaud phenomenon, the transition of Raynaud phenomenon to systemic
      sclerosis, mechanisms and consequences of vascular injury and dysfunction in
      systemic sclerosis, and therapeutic options. RECENT FINDINGS: Careful clinical
      evaluation using a simple definition of Raynaud phenomenon is the most reliable
      and reproducible method in the diagnosis. Although the assessment of vascular
      function by noninvasive methods is still not sensitive enough for the evaluation
      and follow-up of individual patients, it helps in the differential diagnosis and
      in population studies. Progressive deficiency in vasodilatory capacity of the
      vessels is proposed as a mechanism of Raynaud phenomenon, particularly in
      systemic sclerosis. In addition, decreased fibrinolysis and enhanced coagulation
      pathways undoubtedly contribute to vascular dysfunction. The mechanism of
      endothelial injury is still elusive, yet endothelial apoptosis mediated by
      antiendothelial antibodies is the most attractive hypothesis now. Therapies
      directed at the vascular disease continue to focus on the alleviation of vascular
      spasm. However, immunosuppressive therapy may influence the levels of vascular
      injury markers and thus may have an effect on the vascular disease itself.
      SUMMARY: Continued progress in the investigation of the vascular aspects of
      scleroderma is described in this review. Immune involvement in the early stages
      of the disease and mechanism of vascular repair in advance cases are some of the
      highlights of last year's progress.

PMID- 15577611
TI  - Autoantibodies in systemic sclerosis and fibrosing syndromes: clinical
      indications and relevance.
AB  - PURPOSE OF REVIEW: Systemic sclerosis, or scleroderma, is associated with a
      variety of autoantibodies, each of them having their own clinical associations.
      The fibrosing disorders, other than systemic sclerosis, represent a diverse group
      of diseases with systemic or localized effect and with limited understanding of
      their pathogenesis. The purpose of this review is to analyze the literature on
      the clinical usefulness of examining serum autoantibodies in patients with known
      or suspected scleroderma and fibrosing disorders. RECENT FINDINGS: Studies on
      autoantibodies within the past year highlight their clinical utility in systemic
      sclerosis. Anticentromere antibodies are most often seen with limited cutaneous
      involvement and lower frequency of pulmonary fibrosis and lower mortality
      (despite an increased risk for pulmonary hypertension) compared with anti-Scl-70
      and antinucleolar antibodies. Anti-Scl-70 antibodies are associated with diffuse
      cutaneous involvement, increased frequency of pulmonary fibrosis, and higher
      mortality. The anti-polymyositis-scleroderma autoantibody is associated with the
      polymyositis-scleroderma overlap syndrome. Anti-Th/To antibodies are associated
      with milder skin and systemic involvement but with more severe pulmonary fibrosis
      and overall worse prognosis. Anti-RNA-polymerase family antibodies and
      antifibrillarin antibodies are predictive of diffuse cutaneous and systemic
      involvement and greater mortality. Less specific autoantibodies for systemic
      sclerosis and limited data on some other autoantibodies limit their clinical
      utility in patients with systemic sclerosis. For the most part, the association
      between autoantibodies and fibrosing disorders other than systemic sclerosis
      remains inconclusive. SUMMARY: Autoantibodies in systemic sclerosis provide
      important and prognostic information and are useful in defining clinical subsets
      of the disease. When used appropriately, they can be a useful instrument in the
      management of scleroderma.

PMID- 15577612
TI  - Cellular origins of fibroblasts: possible implications for organ fibrosis in
      systemic sclerosis.
AB  - PURPOSE OF REVIEW: There is an intense interest in the potential of circulating
      blood cells and epithelium-related nonfibroblast cells to change into matrix
      synthesizing fibroblasts and myofibroblasts. These sources of fibroblasts may
      have importance in systemic sclerosis (scleroderma). RECENT FINDINGS: Epithelial
      cells from different sources can transition into fibroblasts and myofibroblasts
      in response to transforming growth factor beta and other growth
      factors/cytokines. This is called epithelial-mesenchymal transition (EMT). EMT
      has been repeatedly demonstrated to occur in several models of renal fibrosis
      including lupus prone mice. Quite unexpectedly, bone morphogenic protein 7
      prevents EMT and protects lupus mice and other renal fibrosis models from
      developing fibrosis in the kidneys. Human peripheral blood mononuclear cells
      under different conditions of culture give rise to several different types of
      fibroblast-like cells. In SSc, it has been observed that the sera have low levels
      of serum amyloid protein. Serum amyloid protein has been found to inhibit the
      generation of fibrocytes from CD14 precursors. The implications of these
      potential sources of fibroblasts and myofibroblasts in systemic sclerosis and
      related rheumatic diseases are discussed. SUMMARY: Fibroblasts and myofibroblasts
      in skin and internal organs of patients with systemic sclerosis and related
      diseases may possibly arise not only from the resident fibroblast population but
      from epithelial cells, pericytes, monocytes, and other progenitors from the
      circulating pool of hematopoietic cells and stem cells. These alternative sources
      of fibroblasts would best be treated by specifically targeting the transition or
      transdifferentiation process by which cells change into fibroblasts.

PMID- 15577613
TI  - Recent advances in fibroblast signaling and biology in scleroderma.
AB  - PURPOSE OF REVIEW: Systemic sclerosis is a complex disease manifesting itself by
      fibrosis of skin and other internal organs. Fibroblasts isolated from scleroderma
      lesions and cultured in vitro are characterized by increased synthesis of
      collagen and other extracellular matrix proteins, consistent with the disease
      phenotype. Cultured systemic sclerosis fibroblasts therefore serve as a principal
      experimental model for studying the molecular and cellular mechanisms involved in
      collagen overproduction in this disease. This review will discuss recent findings
      related to intracellular signal transduction pathways implicated in deregulated
      extracellular matrix deposition by systemic sclerosis fibroblasts. RECENT
      FINDINGS: Recent findings suggest that constitutively elevated synthesis of
      extracellular matrix by cultured systemic sclerosis fibroblasts is, at least in
      part, due to the aberrant activation of the autocrine transforming growth factor
      beta signaling. Enhanced constitutive transforming growth factor-beta signaling
      may result from the elevated levels of transforming growth factor-beta receptor
      type I and/or inappropriate activation of Smad3. These alterations of the
      transforming growth factor-beta signaling in systemic sclerosis fibroblasts may
      facilitate increased collagen production in vivo even under conditions of low
      ligand availability. However, there exist many inconsistencies among published
      reports regarding the detailed mechanisms of this pathway in systemic sclerosis
      fibroblasts, and additional studies in this area are needed. Other signaling
      molecules implicated in fibrotic phenotype include several members of the protein
      kinase C family, mammalian target of rapamycin, mitogen-activated protein kinase,
      necdin, reactive oxygen species, and sphingolipids. These signaling pathways may
      work in conjunction with transforming growth factor-beta signaling to regulate
      the behavior of systemic sclerosis fibroblasts. SUMMARY: Alterations in multiple
      signaling pathways contribute to elevated extracellular matrix synthesis by
      systemic sclerosis fibroblasts. Improved understanding of the key signaling
      molecules may provide a novel avenue for therapeutic interventions.

PMID- 15577616
TI  - Bibliography. Current world literature. Myositis and myopathies.

PMID- 15577614
TI  - Animal models of systemic sclerosis: insights into systemic sclerosis
      pathogenesis and potential therapeutic approaches.
AB  - PURPOSE OF REVIEW: Animal models have been extremely valuable in contributing to
      a better understanding of the pathogenesis of systemic sclerosis. Discussed here
      are recent studies that have examined the molecular pathways and potential
      therapeutic approaches for systemic sclerosis using animal models. RECENT
      FINDINGS: Reported evidence further indicates that the immune system plays a role
      in modulating the fibrosis observed in the tight skin-1/+ mouse model for
      systemic sclerosis. CD19, interleukin-6, and interleukin-4 are involved. The
      injection of spleen cells into immune-compromised mice resulted in fibrotic,
      vascular, and immunologic alterations quite similar to those of systemic
      sclerosis. Transforming growth factor-beta and its signaling pathway (JAK kinase
      and STAT-6, Smad2/3, and Smad7) appear to play a central role in the development
      of fibrosis as well as monocyte chemoattractant protein-1, CCR-2, platelet
      derived growth factor C, and excessive apoptosis. Viruses were shown to be
      possible cofactors. The therapeutic agents hepatocyte growth factor and
      halofuginone were shown to prevent fibrosis in animal models of systemic
      sclerosis. SUMMARY: The transforming growth factor-beta signaling pathway is a
      common mechanism of tissue fibrosis in animal models of systemic sclerosis,
      although numerous additional molecules modulate this pathway or have a direct
      effect on fibrosis.

PMID- 15577617
TI  - Treating people with intercurrent infection in HIV prevention trials. Report from
      a WHO/UNAIDS consultation, Geneva 17-18th July 2003.
AB  - While broad agreement now exists among sponsors of HIV prevention trials that
      antiretroviral therapy (ART) and a clinical care package should be provided to
      those who become infected during the conduct of a trial, certain practical issues
      remain unresolved, including Who should pay for ART? How long should ART be
      provided for? Does treatment extend outside of ART? What else should be included
      in the standard of care package and who should pay for it? Who should provide
      treatment and care? This report summarizes the discussions from a consultation
      held in Geneva (17-18 July 2003) organized by the World Health Organization (WHO)
      and the joint United Nations Programme on HIV/AIDS (UNAIDS). The group discussed
      issues related to the various types of HIV prevention trials covered - vaccines,
      microbicides, behavioural - the ethics and legal rational for providing treatment
      and care as well as relevant economic issues and developments around scale-up of
      treatment and care in middle- and lower-income countries. Also discussed were
      policies of certain research agencies, countries and international funding
      agencies. The implementation of the conclusions which came out of these
      discussions on the treatment and care for people who become infected during HIV
      prevention trials requires the active participation of members of the research
      community, funders of research, local and national governments and industry as
      well as the individuals or communities participating in the trials.

PMID- 15577618
TI  - The HIV Netherlands Australia Thailand research collaboration: lessons from 7
      years of clinical research.

PMID- 15577619
TI  - Assessment of longitudinal changes in HIV-specific effector activity in subjects
      undergoing untreated primary HIV infection.
AB  - BACKGROUND: Despite the failure of HIV-specific cell-mediated immune responses to
      clear the virus, these cells play a critical role in the control of viral
      replication throughout HIV infection. OBJECTIVE: To characterize the natural
      evolution of the HIV-specific immune response in HIV primary infection (PI).
      METHODS: Untreated individuals, recruited in HIV PI, were monitored for the
      evolution of HIV-specific immune responses starting in early HIV disease.
      Longitudinal analysis of changes in the magnitude and breadth of HIV-specific
      responses to a panel of MHC class I-restricted peptides was performed using the
      quantitative interferon-gamma ELISPOT assay. RESULTS: Although immune responses
      were detected in all individuals at all times tested, the pattern of the immune
      responses differed significantly from that seen in subjects treated in PI.
      Untreated PI subjects exhibited dramatic changes with time in the frequency of
      individual HIV peptide-specific T-cell responses. In contrast HIV-specific
      immunity was stable in subjects treated in early PI or decreased in intensity and
      breadth in individuals treated later in PI. In untreated subjects the overall
      magnitude of HIV-specific reactivity persisted over at least 12 months whereas
      the number of peptides recognized declined. CONCLUSION: Given that a significant
      relationship existed between the magnitude of the HIV-specific response and viral
      load, it is likely that these effector cell expansions and contractions are
      driven by changes in antigen load.

PMID- 15577620
TI  - Interleukin-2 therapy restores CD8 cell non-cytotoxic anti-HIV responses in
      primary infection subjects receiving HAART.
AB  - OBJECTIVE: To determine the effect of interleukin-2 (IL-2) therapy on immunologic
      and virologic responses in subjects with acute or recent HIV infection already
      receiving highly active antiretroviral therapy (HAART). METHODS: The effect of IL
      2 therapy on immunologic and virologic responses was studied in 21 acutely
      infected individuals who had been receiving HAART for 48 weeks following acute or
      recent HIV infection. Nine subjects receiving no therapy served as controls.
      Viral loads, as well as CD4 and CD8 cell counts were monitored and the CD8 cell
      non-cytotoxic anti-HIV response (CNAR) was measured. RESULTS: IL-2 therapy led to
      significant increases in CD4 cell numbers (P = 0.005) that were maintained for 6
      months after discontinuation of the IL-2 treatment. No effect of IL-2 was
      observed on viral loads or the CD8 cell numbers as compared to subjects receiving
      HAART alone. CNAR activity was restored among subjects receiving HAART and IL-2
      whereas CNAR declined among those receiving HAART alone and in untreated infected
      subjects. The percentage of HAART subjects with CD8 cells showing at least 50%
      suppression of HIV replication increased significantly following IL-2 therapy (P
      = 0.02) and persisted for 6 months. CONCLUSIONS: In primary HIV infection
      administering IL-2 concomitant with HAART following 1 year of treatment with
      HAART gives a significant increase in CD4 cells and a previously unrecognized
      beneficial effect on the CD8 cell non-cytotoxic anti-HIV response.

PMID- 15577621
TI  - T-cell function after interleukin-2 therapy in HIV-infected patients is
      correlated with serum cortisol concentrations.
AB  - OBJECTIVES: To examine the effects of interleukin (IL)-2 therapy on in-vitro
      lymphocyte responsiveness in HIV-infected patients and to correlate these data
      with serum cortisol concentrations. DESIGN: German prospective study. METHODS: In
      adult patients (n = 32) treated with 9 x 10(6) IU/day interleukin-2, lymphocyte
      transformation tests (LTT), serum cortisol concentrations and CD4 T-cell counts
      were assessed before, during and after IL-2 therapy. RESULTS: A significant
      decrease in responses towards mitogens and recall antigens (P < 0.05) was
      observed on day 7 after starting a 4- to 5-day IL-2 therapy as compared to
      baseline. Serum cortisol levels increased (P < 0.0001) reaching a maximum on day
      4, and were still elevated on day 7 (P < 0.005). CD4 T-cell counts significantly
      decreased with a minimum on day 2 before increasing 2.4-fold above baseline on
      day 7 (P < 0.005 each). A positive correlation (P < 0.05 each) was observed for
      changes in cortisol levels and in LTT mitogen and antigen reactions (both day 7 -
      0), changes in cortisol levels (day 3 - 0) and CD4 cell counts on day 2, and
      corticotrophin releasing hormone test results and LTT antigen reactions on day 7.
      LTT responses, cortisol levels and CD4 T-cell counts returned to baseline on day
      30. CONCLUSION: Serum cortisol concentrations are predictive of functional and
      numerical changes of T cells induced by IL-2 therapy.

PMID- 15577622
TI  - Levels and patterns of neutrophil cell counts over the first 8 years of life in
      children of HIV-1-infected mothers.
AB  - BACKGROUND: Antiretroviral drugs (ARV) as prophylaxis to prevent mother-to-child
      transmission of HIV results in decreased haematological parameters during and
      shortly after exposure, with recent data suggesting a more prolonged inhibition
      of haematopoiesis until at least 18 months. DESIGN: Data on 156 HIV-infected and
      1533 uninfected children in the European Collaborative Study followed from birth
      until at least 8 years of age. METHODS: Smoothers and splines were used to
      elucidate patterns over age; linear mixed effects allowed for repeated
      measurements. Covariates included the child's HIV-1 infection status,
      prematurity, gender, race, drug withdrawal symptoms at birth and ARV exposure;
      effects on neutrophil count were quantified in regression analyses using z-scores
      (SD from mean) of neutrophil counts obtained after modelling untransformed values
      using the LMS method. For HIV-infected children, progression to AIDS and ARV
      therapy were also included. RESULTS: After approximately 4 months of age,
      neutrophil counts were consistently and substantially lower in HIV-infected
      children than in uninfected children; in both groups, black children had
      significantly lower counts than white children across the whole age range. In
      uninfected children, male gender and ARV exposure were associated with reduced
      neutrophil count until at least 8 years of age. In HIV-infected children,
      advanced disease and ARV treatment were significantly associated with neutrophil
      count. CONCLUSION: A considerably longer effect of exposure to ARV was shown in
      uninfected children than previously thought and significant associations were
      shown between race and gender and neutrophil count, as previously observed for
      lymphocyte counts. The clinical relevance of these reduced levels of neutrophils
      requires further investigation.

PMID- 15577623
TI  - Multiple mutations in human immunodeficiency virus-1 integrase confer resistance
      to the clinical trial drug S-1360.
AB  - OBJECTIVES: Study of HIV-1 resistance development to the diketo analogue S-1360,
      the first HIV-1 integrase strand transfer inhibitor that has entered clinical
      development. DESIGN: HIV-1(IIIB) was passaged in cell culture in the presence of
      increasing concentrations of S-1360 (IIIB/S-1360(res)). METHODS: The IIIB/S
      1360(res) strains selected for 30, 50 and 70 passages in the presence of S-1360
      were evaluated genotypically by sequencing analysis and phenotypically using the
      MT-4/MTT assay. RESULTS: Multiple mutations, nine in total, emerged progressively
      in the catalytic domain of integrase as a result of the selection process. They
      included T66I and L74M that have both been associated with resistance against the
      diketo acid L-708,906. After 30, 50 and 70 passages in the presence of S-1360,
      IIIB/S-1360(res) displayed a four-, eight- and more than 62-fold reduced
      susceptibility for S-1360, respectively. Phenotypic cross-resistance to L-708,906
      was modest for the IIIB/S-1360(res) strain selected during 50 passages, but
      pronounced for the strain selected during 70 passages. Interesting, all IIIB/S
      1360(res) strains remained fully susceptible to the pyranodipyrimidine V-165, an
      integrase DNA binding inhibitor. Recombination of the mutant integrase genes into
      wild-type background by integrase-chimeric virus technology entirely reproduced
      the resistance profile of the IIIB/S-1360(res) strains. As for the replication
      kinetics of the selected and recombined strains, reduced replication fitness was
      measured for all strains when compared with their respective wild-type strains.
      CONCLUSIONS: The accumulation of integrase mutations coincided with an increasing
      level of (cross-)resistance of IIIB/S-1360(res). Integrase-chimeric virus
      technology confirmed that the integrase mutations are indeed fully responsible
      for the resistance phenotype of IIIB/S-1360.

PMID- 15577624
TI  - Immunologic and clinical responses to highly active antiretroviral therapy over
      50 years of age. Results from the French Hospital Database on HIV.
AB  - OBJECTIVE: To study immunologic and clinical responses to HAART in patients over
      50 years old. DESIGN AND METHODS: A prospective cohort study which included 68
      hospitals in France. A total of 3015 antiretroviral-naive patients, 401 of whom
      were aged 50 years or over, were enrolled following initiation of HAART. The
      influence of age on the mean CD4 cell count increase on HAART was studied by
      using a two-slope mixed model. Progression, defined by the occurrence of a new
      AIDS-defining event (ADE) or death, was studied by Cox multivariate analyses.
      RESULTS: Among patients with baseline HIV RNA above 5 log copies/ml, CD4 mean
      increase during the first 6 months on HAART was +42.9 x 10(6) cells/l per month
      in patients under 50 years and +36.9 x 10(6) cells/l per month in patients over
      50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9
      and +15.6 x 10(6) cells/l per month (P < 0.0001). Similar trends were observed in
      patients with baseline HIV RNA below 5 log copies/ml, and also after
      stratification for the baseline CD4 cell count. After a median follow-up of 31.5
      months, 263 patients had a new ADE and 44 patients died. After adjustment for
      baseline characteristics, older patients had a significantly higher risk of
      clinical progression (hazard ratio (HR) = 1.52 [95% confidence interval (CI),
      1.15-2.00]) and were more likely to achieve a viral load below 500 copies/ml [HR
      = 1.23, (95% CI, 1.11-1.38)]. CONCLUSION: Patients over 50 years of age have an
      immunologic response to HAART. However, their CD4 cell reconstitution is
      significantly slower than in younger patients, despite a better virologic
      response. This impaired immunologic response may explain their higher risk of
      clinical progression.

PMID- 15577625
TI  - Survival in patients with HIV infection and viral hepatitis B or C: a cohort
      study.
AB  - AIM: To assess survival in patients with HIV and viral hepatitis co-infection.
      METHODS: A prospective university clinic cohort of 472 patients with HIV
      infection who were followed for 8343 patient-months. The outcome measures were
      the survival from HIV or liver disease assessed by the Kaplan-Meier method.
      Multivariable analysis using a Cox regression model identified variables
      associated with mortality. RESULTS: Patients were divided into four subgroups:
      HIV/hepatitis B virus (HBV) (n = 72), HIV/hepatitis C virus (HCV) (n = 256),
      multiple hepatitides (n = 18) and HIV alone (n = 126). One hundred and thirty
      four patients (28.4%) died during follow-up. Liver mortality was noted in 55
      patients, representing 12% of the cohort and 41% of the total mortality. Survival
      curves were similar in patients with HIV alone and those with any viral hepatitis
      co-infection. Liver deaths were more common in patients with multiple hepatitides
      (28%) HIV/HBV (15%), HIV/HCV co-infection (13%) versus HIV alone (6%). Liver
      mortality was comparable in HIV/HBV as in HIV/HCV co-infected patients and was
      not associated with gender, ethnicity, age, or mode of infection. HIV deaths were
      similar in patients co-infected with viral hepatitis compared with those with HIV
      alone. In patients with viral hepatitis co-infection, initial CD4 cell count >
      200 x 10(6) cells/l and use of highly active antiretroviral therapy (HAART) were
      associated with significantly reduced liver mortality. CONCLUSIONS: Patients with
      HIV and viral hepatitis had greater liver mortality than patients with HIV alone,
      but had comparable HIV mortality. Co-infection with hepatitis B is associated
      with hepatic outcomes similar to hepatitis C. Control of immunosuppression with
      HAART and CD4 counts > 200 x 10(6) cells/l are associated with better hepatic
      outcomes and should be the first priority in patients with HIV and viral
      hepatitis.

PMID- 15577626
TI  - Long-term safety of discontinuation of secondary prophylaxis against Pneumocystis
      pneumonia: prospective multicentre study.
AB  - OBJECTIVES: To assess the long-term safety of discontinuation of secondary anti
      Pneumocystis prophylaxis in HIV-infected adults treated with antiretroviral
      combination therapy and who have a sustained increase in CD4 cell counts. DESIGN:
      Prospective observational multicentre study. PATIENTS AND METHODS: The incidence
      of P. jirovecii pneumonia after discontinuation of secondary prophylaxis was
      studied in 78 HIV-infected patients on antiretroviral combination therapy after
      they experienced a sustained increase in CD4 cell counts to at least 200 x 10(6)
      cells/l and 14% of total lymphocytes measured twice at least 12 weeks apart.
      RESULTS: Secondary prophylaxis was discontinued at a median CD4 cell count of 380
      x 10(6) cells/l. The median follow-up period after discontinuation of secondary
      prophylaxis was 40.2 months, yielding a total of 235 person-years of follow-up.
      No cases of recurrent P. jirovecii pneumonia occurred during this period. The
      incidence was thus 0 per 100 person-years with a 95% upper of confidence limit of
      1.3 cases per 100 patient-years. CONCLUSIONS: Discontinuation of secondary
      prophylaxis against P. jirovecii pneumonia is safe even in the long term in
      patients who have a sustained immunologic response on antiretroviral combination
      therapy.

PMID- 15577627
TI  - The impact of attending a behavioural intervention on HIV incidence in Masaka,
      Uganda.
AB  - OBJECTIVE: Changing behaviour is an important method for preventing HIV
      infection. We examined why a community randomized trial of a behavioural
      intervention found no significant effect of this on HIV incidence in rural
      Uganda. DESIGN: An individual-level analysis of a community randomized trial.
      METHODS: All sexually active, initially HIV-seronegative individuals with data on
      sexual behaviour were included (1558 men and 1836 women). Uptake of the
      intervention was measured using self-reported attendance at meetings, videos,
      dramas, and interactions with community educators in the past year. Sexual
      behaviour was assessed using self-reported condom use and the number of sexual
      partners in the past year. RESULTS: Overall, 81% of individuals in the
      intervention communities and 9% in the comparison communities reported attending
      at least one of the intervention activities in the past year. Attendance was
      lower in women, in those aged 55 years or older, and in the widowed. There was a
      lower HIV incidence in those who reported attending at least one intervention
      activity compared with those who attended none, and in women this effect was
      statistically significant (in women, adjusted rate ratio 0.41, 95% CI 0.19-0.89,
      P = 0.024; in men, adjusted rate ratio 0.66, 95% CI 0.25-1.79, P = 0.42).
      Reported behaviour change did not differ markedly between those who did and did
      not report attending any intervention activities. CONCLUSION: Although the
      intervention had no significant benefit in the communities as a whole, it
      resulted in a reduced risk of HIV acquisition in women who attended it. The
      methodological implications for future trials are discussed.

PMID- 15577628
TI  - Cost-effectiveness of HIV postexposure prophylaxis following sexual or injection
      drug exposure in 96 metropolitan areas in the United States.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of HIV postexposure prophylaxis
      (PEP) following sexual or injection-related exposures in 96 metropolitan
      statistical areas in the United States (MSA). DESIGN: Empirical, model-based cost
      effectiveness analysis. METHODS: Epidemiological and population size estimates
      from the literature were combined with information about the distribution of
      exposure types, PEP completion rate, proportion of source partners known to be
      HIV infected, and PEP program costs obtained from a feasibility study of PEP in
      San Francisco to estimate the cost-effectiveness of hypothetical PEP programs in
      each of the 96 MSA. The effectiveness of combination antiretroviral therapy
      following sexual or drug use-related exposures, which is presently not known, was
      assumed equal to the effectiveness of zidovudine monotherapy in the occupational
      setting. The main outcome measure was the cost-utility ratio, defined as the cost
      per quality-adjusted life year (QALY) saved by the PEP intervention. RESULTS: The
      cost-utility ratios for the 96 MSA ranged from 4137 dollars to 39,101 dollars per
      QALY saved; only two of the ratios exceeded 30,000 dollars per QALY saved.
      Combined across the 96 MSA, the hypothetical PEP programs would reach nearly
      20,000 clients at a total cost of approximately 22 million dollars. The overall
      cost-utility ratio across MSA was 12,567 dollars per QALY saved. The majority of
      the HIV infections prevented by PEP were among men and women who reported
      receptive anal intercourse exposure. CONCLUSIONS: PEP following sexual or drug
      use-related exposures could be a cost-effective complement to existing HIV
      prevention efforts in most MSA across the United States.

PMID- 15577629
TI  - Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected
      patients with new syphilis infections.
AB  - BACKGROUND: Syphilitic ulcers are known to facilitate the transmission of HIV
      infection, but the effect of syphilis infection on HIV viral loads and CD4 cell
      counts is poorly understood. METHODS: We abstracted medical records for HIV
      infected male syphilis patients seen at three clinics in San Francisco and Los
      Angeles from January 2001 to April 2003. We compared plasma HIV-RNA levels and
      CD4 cell counts during syphilis infection with those before syphilis infection
      and after syphilis treatment, using the Wilcoxon signed rank test. RESULTS: Fifty
      two HIV-infected men with primary or secondary syphilis had HIV viral load and
      CD4 cell count data available for analysis; 30 (58%) were receiving
      antiretroviral therapy. Viral loads were higher during syphilis compared with pre
      syphilis levels by a mean of 0.22 RNA log10 copies/ml (P = 0.02) and were lower
      by a mean of -0.10 RNA log10 copies/ml (P = 0.52) after syphilis treatment. CD4
      cell counts were lower during syphilis infection than before by a mean of -62
      cells/mm3 (P = 0.04), and were higher by a mean of 33 cells/mm3 (P = 0.23) after
      syphilis treatment. Increases in the HIV viral load and reductions in the CD4
      cell count were most substantial in men with secondary syphilis and those not
      receiving antiretroviral therapy. CONCLUSION: Syphilis infection was associated
      with significant increases in the HIV viral load and significant decreases in the
      CD4 cell count. The findings underscore the importance of preventing and promptly
      treating syphilis in HIV-infected individuals.

PMID- 15577630
TI  - How effective is HAART in HCV and HIV coinfection?

PMID- 15577631
TI  - Prospects for an AIDS vaccine: encourage innate immunity.

PMID- 15577632
TI  - HIV-1 Env-specific cytotoxic T-lymphocyte responses in exposed, uninfected Kenyan
      sex workers: a prospective analysis.
AB  - The prospective significance of HIV-specific cytotoxic T lymphocyte (CTL)
      responses in highly exposed, persistently seronegative populations is unknown. In
      1996-1997 we screened for CTL responses against HIV clade B Env in 39 recently
      enrolled Kenyan female sex workers, and followed these women prospectively.
      Annual HIV incidence was 5.8%. CTL were independently associated with age and
      recent HIV-1 exposure,but were not prospectively associated with protection in a
      multivariable model that included HIV-1 exposure and duration of sex work.

PMID- 15577633
TI  - IL-7 and Flt-3L plasma levels are increased during highly active antiretroviral
      therapy-associated IL-2 therapy.
AB  - IL-2 is used in conjunction with highly active antiretroviral therapy to increase
      the CD4 cell count in HIV-positive patients. The mechanisms involved remain ill
      defined. Here we show that during the first cycle of IL-2 therapy, IL-7 and Flt
      3L plasma levels are increased, whereas levels of stem cell factor are unchanged.
      This supports the hypothesis that aside from stimulating CD4 T cells IL-2 may
      also indirectly affect lymphocyte production through the stimulation of
      lymphopoietic cytokines.

PMID- 15577634
TI  - Higher efavirenz concentrations determine the response to viruses carrying non
      nucleoside reverse transcriptase resistance mutations.
AB  - We examined the influence of both efavirenz plasma concentrations and non
      nucleoside reverse transcriptase (NNRTI) resistance mutations on the antiviral
      activity of efavirenz in patients experiencing early virological failure under
      nevirapine-containing regimens. Up to 41% of patients reach less than 50
      copies/ml at 48 weeks. No association was found between the presence of NNRTI
      resistance mutations and virological outcome. Nevertheless, patients responding
      virologically and carrying NNRTI-resistant viruses had higher efavirenz levels
      than those who did not respond.

PMID- 15577635
TI  - Predictors of selection of K65R: tenofovir use and lack of thymidine analogue
      mutations.
AB  - Over the past 5 years, 1846 HIV-infected patients underwent drug resistance
      testing at our institution. None out of 216 drug-naive subjects showed K65R.
      However, it was recognized in 53 out of 1630 antiretroviral-experienced patients
      (3.3%), of whom 10 had never been exposed to tenofovir. The rate of K65R
      increased from 0.6% in 1999 to 11.5% in 2004. The recognition of K65R correlated
      negatively with the presence of thymidine analogue mutations but positively with
      Q151M.

PMID- 15577636
TI  - Heterosexual transmission of multiple highly conserved viral variants in HIV-1
      subtype C-infected seronegative women.
AB  - Viral population diversity was assessed in samples collected from five HIV
      infected women who were RNA positive and antibody negative. Similar to studies in
      men, highly conserved viral variants were detected (mean nucleotide diversity of
      0.11% for p17p24, 0.32% for C2C3). In two individuals diversity was
      uncharacteristically lower in env C2C3 than in gag pl7p24, suggesting selection
      in env at this very early stage of infection.

PMID- 15577637
TI  - Simplified one-step antibody-HLA directed expansion of HIV-specific cytotoxic T
      lymphocytes: a system suited for use in vivo.

PMID- 15577638
TI  - Comments on the review 'Care of patients with hepatitis C and HIV co-infection'
      by Soriano et al.

PMID- 15577640
TI  - Human resources in scaling up HIV/AIDS programmes: just a killer assumption or in
      need of new paradigms?

PMID- 15577641
TI  - Addressing the educational void during the antiretroviral therapy rollout.

PMID- 15577642
TI  - Motor-biking through rural India on an HIV mission.

PMID- 15577643
TI  - Phylogenetic analysis of HIV-1 transmission: pol gene sequences are insufficient
      to clarify true relationships between patient isolates.

PMID- 15577644
TI  - CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV
      drugs in vitro.
AB  - OBJECTIVE: To evaluate the anti-HIV-1 activity of the cyclotriazadisulfonamide
      CADA against primary isolates in vitro and the combination of CADA with approved
      anti-HIV drugs for potential synergy. METHODS: Peripheral blood mononuclear cells
      (PBMC) were treated with CADA and infected with 16 different clinical isolates.
      After 8 days of infection, the median inhibitory concentration (IC50) was
      calculated from the p24 viral antigen content in the supernatant. MT-4 cells were
      infected with HIV-1NL4.3 and then cultured with CADA or other antiretroviral
      drugs (i.e., several reverse transcriptase, protease and entry inhibitors), alone
      and in combination. After 4 days, IC50 was determined for the various drugs in
      replicate assays. Analysis of combined effects was performed using the median
      effect principle (CalcuSyn; Biosoft). RESULTS: The entry inhibitor CADA exerted a
      potent and consistent anti-HIV-1 activity against a wide range of R5, R5/X4 and
      X4 primary isolates in PBMC. From the two-drug studies, combination indices
      showed synergy between CADA and reverse transcriptase inhibitors (zidovudine,
      stavudine, lamivudine, zalcitabine, didanosine, abacavir, tenofovir, nevirapine,
      delavirdine and efavirenz), and protease inhibitors (lopinavir, saquinavir,
      indinavir, nelfinavir, amprenavir and ritonavir). In addition, the combination of
      CADA with the gp41 fusion inhibitor T-20 (enfuvirtide), the CXCR4 antagonist
      AMD3100 and the gp120-specific interacting plant lectins from Galanthus nivalis
      (GNA) and Hippeastrum hybrid (HHA) also resulted in a synergistic inhibition.
      CONCLUSIONS: Compounds that can specifically downmodulate the CD4 receptor in
      PBMC have broad-spectrum anti-HIV activity against primary isolates and act
      synergistically when used in conjunction with currently available antiretroviral
      drugs. They deserve further study as potential candidate anti-HIV drugs.

PMID- 15577645
TI  - The HIV-1 nucleoside reverse transcriptase inhibitors stavudine and zidovudine
      alter adipocyte functions in vitro.
AB  - OBJECTIVES: Nucleoside analogues are suspected of playing a role in peripheral
      fat loss in patients during long-term treatment with antiretroviral drugs. DESIGN
      AND METHODS: We compared the long-term effects of stavudine (10 microM),
      zidovudine (1 muM), didanosine (10 microM), abacavir (4 microM), lamivudine (10
      microM), and tenofovir (1 microM), near their maximum concentration values, on
      the differentiation, lipid accumulation, survival and mitochondrial function of
      differentiating 3T3-F442A and differentiated 3T3-L1 adipocytes. RESULTS: None of
      the nucleoside reverse transcriptase inhibitors (NRTI) markedly altered the
      differentiation of 3T3-F442A cells, as shown by the unmodified percentage of
      cells with lipid droplets on day 7 and the expression of the early
      differentiation markers CCAAT/enhancer binding protein (C/EBP) beta (on day 2)
      and sterol regulatory element-binding protein. However, stavudine and zidovudine
      altered the lipid phenotype, decreasing the lipid content and expression of
      markers involved in lipid metabolism, namely C/EBPalpha, peroxisome proliferator
      activated receptor gamma, adipocyte lipid binding protein 2, fatty acid synthase
      and acetyl-coenzyme A carboxylase. Stavudine and zidovudine, contrary to the
      other NRTI, drove 5-10% of 3T3-F442A cells towards apoptosis, and reduced the
      lipid content and survival of differentiated 3T3-L1 adipocytes. Stavudine and
      zidovudine increased mitochondrial mass by two to fourfold, and lowered the
      mitochondrial membrane potential (JC-1 stain) as did zalcitabine (0.2 microM). Co
      treatment with zidovudine plus lamivudine, or zidovudine plus lamivudine and
      abacavir, did not increase the effect of zidovudine on cell viability or
      apoptosis. CONCLUSION: The thymidine analogues stavudine and zidovudine decreased
      lipid content, mitochondrial activity, and adipocyte survival in vitro.

PMID- 15577646
TI  - The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on
      insulin sensitivity in HIV-seronegative healthy adults.
AB  - BACKGROUND: Therapy with some HIV protease inhibitors (PI) contributes to insulin
      resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive
      glucose transporters. Atazanavir (ATV) is a new PI with substantially less in
      vitro effect on glucose transport than observed with other PI, including
      lopinavir (LPV) or ritonavir (RTV). METHODS: Randomized, double-blind, crossover
      study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r)
      or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative
      subjects. Each subject was studied on two of three possible treatments with a
      wash-out period between treatments. RESULTS: The mean insulin-stimulated glucose
      disposal (mg/min per kg body weight) per unit insulin (microU/ml) (M/I) was 9.88,
      9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There
      was no significant difference between ATV and placebo. The M/I for LPV/r was 23%
      lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P =
      0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg
      for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no
      significant difference between ATV and placebo. The glycogen storage rate for
      LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006).
      CONCLUSIONS: ATV given to healthy subjects for 5 days did not affect insulin
      sensitivity, while LPV/r induced insulin resistance. This observation is
      consistent with differential in vitro effects of these PI on glucose transport.
      Further data are needed to assess clinical implications for body composition.

PMID- 15577647
TI  - Late presenters in the era of highly active antiretroviral therapy: uptake of and
      responses to antiretroviral therapy.
AB  - OBJECTIVES: To investigate the characteristics and clinical, immunological and
      virological outcomes for individuals presenting for care with low CD4 cell
      counts. METHODS: Individuals aged > 16 years presenting for care for the first
      time were identified between 1 January 1996 and 31 December 2002. Late presenters
      were those with CD4 cell count < 50 x 10(6) cells/l. Follow-up was until last
      contact, death or 31 December 2002. RESULTS: Late presenters formed 15.3% (110)
      of the group; they were more likely to be female (35% versus 24%), heterosexual
      (53% versus 38%), and of Black-African ethnicity (39% versus 27%) than other
      individuals. Over a median follow-up of 2.5 years, 13% of late presenters died.
      Ninety-nine patients started antiretroviral treatment; Of the 11 patients who did
      not start antiretroviral treatment, eight died within 3 months of presentation.
      Among those starting treatment, 87 (87.9%) achieved a viral load < 400 copies/ml
      and median CD4 cell counts increased from 43 x 10(6) cells/l at 0-2 months after
      presentation to 204 x 10(6) cells/l at 1 year. Over the first year, 71 patients
      attended at least one outpatient visit (median, 4.5; range, 0-39), 21 attended at
      least one day case visit (median, 0; range, 0-15) and 49 were admitted as an
      inpatient (median, 0; range, 0-4). CONCLUSIONS: Those presenting for care with
      very low CD4 cell counts may make large demands on clinical resources,
      particularly over the first few months. While some patients do have a poor
      outcome on highly active antiretroviral therapy, many will benefit from this
      therapy and will experience good immunological and virological responses.

PMID- 15577648
TI  - Limited benefit of antiretroviral resistance testing in treatment-experienced
      patients: a meta-analysis.
AB  - OBJECTIVE: To estimate the effectiveness of resistance assessments based on viral
      sequencing (genotypic antiretroviral resistance testing, GART), phenotypic
      antiretroviral resistance testing (PART) or virtual PART (vPART) in the
      management of treatment-experienced HIV-1-infected patients. DESIGN: Meta
      analysis of randomized controlled trials comparing treatments aided by GART, PART
      and vPART, and controls. METHODS: The meta-analysis synthesized data on the
      proportion of patients with undetectable plasma viral load, the decrease in viral
      load, and the increase in CD4 cell count at 3 and 6 months after randomization.
      RESULTS: Ten trials were analyzed (total 2258 participants). Compared with
      controls, at 3 and 6 months GART increased the proportion of patients with viral
      load below detection by 11% [95% confidence interval (CI), 6-16], and 10% (95%
      CI, 5-16), respectively. The difference in viral load change was 0.27 log10
      copies/ml (95% CI, 0.11-0.43) and 0.21 log10 copies/ml (95% CI, 0.09-0.34),
      respectively. However, no improvement was observed in the CD4 cell count at
      either time point: the difference in CD4 cell count -5.7 x 10(6) cells/l (95% CI,
      -18.8 to 7.3) and 1.2 x 10(6) cells/l (95% CI, -15.0 to 17.4), respectively, at 3
      and 6 months. For PART, there was no clear evidence for any benefit versus no
      testing (three trials). vPART conferred a small benefit in indirect comparisons
      versus no testing. CONCLUSION: Evidence for benefit of antiretroviral resistance
      testing is sparse and limited to small short-term improvements of virologic
      response, mostly with GART and less with vPART. Current guidelines widely
      recommending the use of antiretroviral resistance testing in clinical practice
      are not commensurate with the available evidence.

PMID- 15577649
TI  - Impact of antiretroviral treatment on progression of hepatic fibrosis in
      HIV/hepatitis C virus co-infected patients.
AB  - BACKGROUND: The impact of immune reconstitution on liver fibrosis in
      HIV/hepatitis C virus (HCV) patients is unknown. In this case-control study, we
      investigated the impact of HIV infection on the severity of liver fibrosis and
      identified related factors. METHODS: We studied 116 HIV/HCV patients and 235 HCV
      only patients all untreated for HCV. Each co-infected patient was matched with
      two singly-infected patients according to gender, age at contamination and
      duration of infection. Liver biopsy was analysed using the METAVIR score.
      RESULTS: Alcohol consumption and route of contamination differed between HCV
      infected and HCV/HIV co-infected patients. Among co-infected patients, a F3-F4
      Metavir score was significantly more frequent than in mono-infected patients. Co
      infected patients with severe fibrosis (F3-F4) had higher transaminase, ferritin
      levels and lower CD4 T-cell count than patients with none to moderate fibrosis
      (F0-F2). Although median duration of treatment with nucleoside analogues, non
      nucleoside analogues and protease inhibitors were comparable in both groups, the
      delay between the presumed date of contamination and treatment initiation with
      highly active antiretroviral therapy (HAART) was significantly longer for
      patients with severe fibrosis than those with none to moderate fibrosis. Finally,
      the mean rate of fibrosis progression was significantly slower among patients
      exposed to HAART. CONCLUSION: Early antiretroviral therapy in co-infected HIV-HCV
      patients may slow liver fibrosis progression.

PMID- 15577650
TI  - Factors associated with chronic renal failure in HIV-infected ambulatory
      patients.
AB  - OBJECTIVE: Renal disease is an increasingly common manifestation among HIV
      positive persons, particularly during late stages of HIV disease. We performed a
      cohort-based, nested case-control study to examine the role of several factors in
      developing HIV-related chronic renal disease, including HIV viral load and CD4+
      cell count. DESIGN: Incident cases of chronic renal disease were identified from
      a cohort of 6361 prospectively followed HIV-1 positive persons. Controls were
      selected using incidence density sampling and matched 4:1 on age, race/ethnicity,
      and gender. METHODS: Odds ratios (OR) and 95% confidence intervals (CI) were
      obtained using conditional logistic regression. RESULTS: One hundred and eight
      cases of chronic renal disease were identified; 80 (74.1%) were eligible for the
      current analysis. Nadir CD4+ cell count < 200 x 10(6) cells/l (OR = 4.3; 95% CI,
      2.1-8.7), highly active antiretroviral therapy (HAART) use for 56 days or more
      (OR = 0.5; 95% CI, 0.3-1.0), and hypertension [treated with angiotensin
      converting enzyme (ACE) inhibitors: OR = 4.6; 95% CI, 1.8-11.6; treated with non
      ACE inhibitors: OR = 2.5; 95% CI, 1.0-6.2; not treated: OR = 4.2; 95% CI, 0.8
      21.6] were associated with disease. HAART use for 56 days or more modified the
      associations for nadir CD4+ cell count and hypertension. CONCLUSIONS: Our
      findings suggest that advanced HIV-disease, as indicated by low CD4+ cell count,
      is associated with subsequently developing chronic renal disease and treatment
      with HAART may reduce the risk of developing chronic renal disease.

PMID- 15577651
TI  - Hormonal contraception and risk of cervical infections among HIV-1-seropositive
      Kenyan women.
AB  - OBJECTIVE: To evaluate the relationship between hormonal contraceptive use and
      the acquisition of cervical sexually transmitted infections (STI) among HIV-1
      infected women. DESIGN: A prospective cohort study of 242 commercial sex workers
      in Mombasa, Kenya, followed from the time of HIV-1 infection. METHODS: At monthly
      follow-up visits, sexual behavior and contraceptive use were recorded, and
      laboratory screening for STI was performed. Multivariate Andersen-Gill
      proportional hazards models were constructed to examine the association between
      the use of hormonal contraception and the occurrence of cervical STI. RESULTS:
      The median duration of follow-up after HIV-1 acquisition was 35 months, and 799
      person-years of follow-up were accrued. After adjustment for demographic factors
      and sexual behavior, women using the injectable contraceptive depot
      medroxyprogesterone acetate were at increased risk of Chlamydia trachomatis
      infection [hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.4, P = 0.05]
      and cervicitis (HR 1.6, 95% CI 1.0-2.3, P = 0.03) compared with women using no
      contraception. The use of oral contraceptive pills was associated with an
      increased risk of cervicitis (HR 2.3, 95% CI 1.4-3.8, P = 0.001). Hormonal
      contraception was not associated with an increased risk of infection with
      Neisseria gonorrhoeae. CONCLUSION: The use of hormonal contraception by HIV-1
      infected women was associated with an increased risk of cervicitis and cervical
      chlamydia infection. HIV-1-seropositive women using hormonal contraception should
      be counseled about the importance of consistent condom use to prevent both STI
      and HIV-1 transmission.

PMID- 15577652
TI  - Antiretroviral resistance and high-risk transmission behavior among HIV-positive
      patients in clinical care.
AB  - BACKGROUND: HIV-positive patients receiving antiretroviral therapy (ART) who
      engage in HIV transmission behaviors may harbor and transmit drug-resistant HIV.
      However, little is known about the risk behaviors of these patients, potential
      partners exposed and the relationship of these to ART resistance. OBJECTIVE: To
      determine the relationship of HIV drug resistance and continuing HIV transmission
      risk behavior among HIV-positive patients in care. METHODS: A retrospective,
      cross-sectional study of HIV transmission risk behavior and HIV drug resistance
      data from 333 HIV-positive patients. RESULTS: Among a diverse population of 333
      HIV-positive patients, 75 (23%) had unprotected sex during the previous 3-months,
      resulting in 1126 unprotected sexual events with 191 partners of whom 155 were
      believed by patients to be HIV-negative or of unknown status. Eighteen of the 75
      (24%) had resistant HIV and 207 unprotected sexual events, exposing 18% of the
      HIV- or status unknown partners. There was no difference in the proportion of
      patients engaging in unprotected sex who had undetectable viral load (VL) (22%):
      VL > 400 copies/ml without resistance (20%) and VL > 400 copies/ml with
      resistance (26%). Resistance and risk behavior was predicted only by lower mental
      health scores (odds ratio, 10.3; 95% confidence interval, 1.7-18.6). CONCLUSION:
      A substantial minority (23%) of patients in clinical care engaged in HIV sexual
      transmission risk behavior. A small subset of these also had ART-resistant HIV.
      However, this core group (approximately 5% of all patients) accounted for a large
      number of high-risk HIV transmission events with resistant virus, exposing a
      substantial number of partners.

PMID- 15577653
TI  - Nonoxynol-9 100 mg gel: multi-site safety study from sub-Saharan Africa.
AB  - OBJECTIVES: To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal
      microbicide, on the genital mucosa of women from Malawi and Zimbabwe in
      preparation for a phase III efficacy study. METHODS: HIV-uninfected women (180)
      were enrolled and randomized to either N-9 or placebo gel and instructed to
      insert gel into the vagina twice daily for 14 days. Follow up examinations were
      conducted at 7 and 14 days. RESULTS: The number of adverse events in the N-9 gel
      group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported
      number of any genital symptoms was significantly higher in the N-9 group (38% N
      9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher
      in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers
      and abrasions in the N-9 group was low (2% and 3%, respectively) and not
      different from that in the placebo group (1% and 2%, respectively). CONCLUSIONS:
      N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and
      epithelial disruptions compared with placebo. The clinical significance of these
      epithelial disruptions is unknown. Although these findings alone were not
      sufficient to cancel the planned phase III study, when considered together with
      the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel,
      the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.

PMID- 15577654
TI  - Locking the door to HIV entry: how far can we go?

PMID- 15577655
TI  - Tetanus vaccination with IL-2 during highly active antiretroviral therapy induces
      sustained and pronounced specific CD4 T-cell responses.
AB  - HIV-1 infection results in profound dysfunction of the CD4 T-cell population.
      Although highly active antiretroviral therapy allows the reconstitution of CD4 T
      cell numbers, functional abnormalities remain, including inadequate responses to
      vaccination. IL-2 increases CD4 T-cell numbers and function. We report the
      effects of IL-2 given with tetanus vaccination in two patients in a larger
      immunotherapy study. In one case IL-2 induced sustained responses, which may have
      been caused by the timing of IL-2 with vaccination.

PMID- 15577656
TI  - HIV viral shedding in semen: lack of correlation with systemic virus-specific CD8
      responses.
AB  - Semen is a major transmission vector for HIV. Virus-specific CD8 T cells are
      critical in HIV control, but their relationship with semen viral load is unknown.
      We therefore examined the association between systemic HIV-specific IFN-gamma CD8
      responses and viral load in the semen and blood of HIV-infected men. No
      correlation was observed between viral load in either semen or blood and systemic
      CD8 T-cell responses. Further studies of immune correlates of semen HIV shedding
      are needed.

PMID- 15577657
TI  - Impact of a treatment including tenofovir plus didanosine on the selection of the
      65R mutation in highly drug-experienced HIV-infected patients.
AB  - Data from 20 highly drug-experienced HIV-infected patients receiving tenofovir
      plus didanosine as part of a salvage regimen were analysed. At baseline, all but
      one patient harboured a virus bearing at least one nucleoside excision mutation
      (NEM); in 13 cases (65%) three or more NEM were detectable. After a median of 26
      weeks of treatment, two patients (10%) selected the 65R mutation. These results
      support the hypothesis that NEM hinder the selection of this mutation.

PMID- 15577658
TI  - Comparison of point-of-care rapid HIV testing in three clinical venues.
AB  - Rapid HIV testing with same-visit results should increase the number of
      individuals who know they are HIV infected. We assessed the acceptability and
      feasibility of point-of-care rapid testing in three public venues, a sexually
      transmitted disease clinic, a county jail, and an emergency department. Over 98%
      of all participants received their results, and 82% of newly identified HIV
      positive participants entered care. Point-of-care rapid testing was feasible,
      acceptable, and may improve entry into care.

PMID- 15577659
TI  - CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected
      patients: the role of intravenous drug use.
AB  - We evaluated the impact of HIV risk practice on immune reconstitution in a
      prospective cohort of 288 patients (176 former injecting drug users) who
      maintained complete virus suppression for more than 24 months. Significant
      differences in CD4 cell counts at 6 and 24 months were detected. Multivariate
      analysis showed that drug use was an independent predictor of poor immunological
      recovery. Injection drug abuse impairs short and long-term CD4 cell recovery in
      HIV-positive patients initiating successful highly active antiretroviral therapy.

PMID- 15577660
TI  - Long-term efficacy after switch from protease inhibitor-containing highly active
      antiretroviral therapy to abacavir, lamivudine, and zidovudine.

PMID- 15577661
TI  - Reactive iris lymphoid proliferation presenting as the AIDS-defining event in an
      HIV patient with systemic lymphoma.

PMID- 15577662
TI  - HIV treatment optimism and high-risk sexual behaviour among gay men: the
      attributable population risk.

PMID- 15577663
TI  - Cryptococcosis in HIV-infected individuals.

PMID- 15577664
TI  - An intravenous medication safety system: preventing high-risk medication errors
      at the point of care.
AB  - Improving medication safety at the point of care--particularly for high-risk
      drugs--is a major concern of nursing administrators. The medication errors most
      likely to cause harm are administration errors related to infusion of high-risk
      medications. An intravenous medication safety system is designed to prevent high
      risk infusion medication errors and to capture continuous quality improvement
      data for best practice improvement. Initial testing with 50 systems in 2 units at
      Vanderbilt University Medical Center revealed that, even in the presence of a
      fully mature computerized prescriber order-entry system, the new safety system
      averted 99 potential infusion errors in 8 months.

PMID- 15577665
TI  - Low health literacy and its effects on patient care.

PMID- 15577666
TI  - Clinical nurses' understanding of autonomy: accomplishing patient goals through
      interdependent practice.
AB  - OBJECTIVE: The purpose of the study was to enable nurse managers to identify
      strategies to support and enhance autonomous practice based on clinical nurses'
      understanding of autonomy. BACKGROUND: Findings from an organizational work-life
      satisfaction survey led a nursing management team to question how clinical nurses
      understand autonomy. The nursing literature offers inconsistent definitions of
      autonomy and interchangeable use of related concepts. METHODS: Twelve focus
      groups involving 43 nurses working in cardiovascular service units discussed
      instances of satisfaction and dissatisfaction with autonomy in their clinical
      practice and work life. Verbatim transcripts of group discussions were
      interpreted by a research team to identify salient examples and descriptions of
      autonomy. RESULTS: Nurses described autonomy as their ability to accomplish
      patient care goals in a timely manner by using their knowledge and skills to
      understand and contribute to the overall plan of care; assess patient needs and
      conditions; effectively communicate concerns and priorities regarding patient
      care; and access and coordinate the resources of the multidisciplinary team.
      CONCLUSIONS: These findings challenge assumptions about autonomy as independent
      decision making and practice. They highlight nurses' contributions to patient
      care goals through knowledge of how to get things done within hospital systems
      and through interdisciplinary coordination and collaboration.

PMID- 15577667
TI  - Nurses Improving Care to Health System Elders (NICHE): implementation of best
      practice models.
AB  - Nurses Improving Care to Health System Elders (NICHE) is a comprehensive program
      that hospitals use to foster system-wide improvements in the care of older
      patients. The authors report on a survey of 103 NICHE hospitals to determine
      perceptions of the NICHE program, the adoption of NICHE models and protocols, and
      the educational outcomes, policy changes, and benchmarks related to care of older
      patients established by the participating NICHE hospitals.

PMID- 15577668
TI  - Evaluating the chief nurse executive: reflections on the process.
AB  - Performance improvement of chief nurse executives (CNEs) is an integral part of a
      healthcare organization's program of continuous improvement. However, the process
      of evaluating CNEs is an increasingly complex and costly one. This is, in part,
      because the formal evaluation process for a CNE of a stand-alone hospital
      building is considerably different from that of a CNE in an integrated health
      care system of hundreds or several thousand nursing personnel. Reflecting on
      staff's perceptions of the CNE evaluation process in a large system, the author
      highlights major concerns related to issues of trust, their careers, the
      organization, their patients, and themselves.

PMID- 15577669
TI  - Is your nursing staff ready for magnet hospital status? An application of the
      revised Nursing Work Index.
AB  - There has been a slow, steady exodus of nurses from the acute care setting.
      However, magnet hospital status is closely correlated with increased retention of
      nursing staff. The author outlines an assessment plan for nursing staff to
      determine if magnet status application efforts may be successful for an
      organization.

PMID- 15577670
TI  - Creating a healthy workplace: a participatory organizational intervention.
AB  - Participatory research is, in theory, an approach that is attractive and easy to
      apply. However, in practice this type of research poses numerous challenges. This
      article presents recent information on healthcare workers who have experienced a
      participatory organizational intervention aimed at reducing the work constraints
      and creating a healthy workplace. Three main challenges emerged from this
      experience: mobilizing the team and creating a relationship of trust among the
      participants; creating a healthy organization in partnership with those in other
      professions; and implementing the proposed changes.

PMID- 15577671
TI  - Emergency preparedness competencies: assessing nurses' educational needs.
AB  - This article reports findings from a research study designed to assess the level
      of familiarity Wisconsin nurses have regarding their response to large-scale
      emergency events. The research process identified 8 emergency preparedness
      dimensions, which were then investigated in the study. Efforts were also
      undertaken to determine the types of educational offerings and class-scheduling
      options most preferred by nurses.

PMID- 15577672
TI  - Urothelial carcinoma of the renal pelvis: a clinicopathologic study of 130 cases.
AB  - Urothelial carcinomas of the renal pelvis are relatively rare tumors, and large
      series that include clinicopathologic and outcome data are few. We reviewed 130
      consecutive nephroureterectomies performed for urothelial carcinoma of the renal
      pelvis at our institution. Tumors were graded using the World Health
      Organization/International Society of Urologic Pathologists (WHO/ISUP) grading
      system and were staged according to the 2002 TNM classification; 83 (63.6%) of
      the patients were men and 47 (36.4%) were women. The mean age at diagnosis was 67
      years (range, 41-93 years). The average tumor size was 3.7 cm; 36 of the cases
      were multifocal and 5 were bilateral. Lower tract disease occurred in 50.7% (66
      cases); 38 of the cases (29.3%) were low grade and the remaining 92 (70.7%) were
      high grade. A total of 50% of the cases were pTis, pTa, or pT1, while 45% invaded
      deeply (pT2 or more). Depth of invasion could not be assessed with certainty in 7
      cases (5%). Regional lymph nodes were identified/submitted in only 50 cases. Of
      those, 12 cases (24%) had lymph node metastasis. Follow-up information was
      available in 125 (96%) patients. The period of follow-up ranged from 1 week to
      176 months (mean, 48.9 months). At last follow-up, 47 patients (36%) had died of
      other causes, 18 (13.8%) were dead of disease, 8 patients (6%) were alive with
      disease, and 52 patients (40%) were alive with no evidence of disease. In
      univariate analysis, histologic grade (P = 0.001), TNM stage (P = 0.0001),
      vascular invasion (P = 0.001), margin status (P = 0.021), and size (P = 0.0003)
      were significantly associated with survival. On multivariate analysis, TNM stage
      (P = 0.03) was the only variable associated with survival. In conclusion, our
      study shows that a high percentage of the urothelial carcinoma of the renal
      pelvis present with locally advanced (pT2 or more) disease at the time of
      nephroureterectomy. Pathologic stage is the most potent predictor of survival,
      similar to lower tract disease. A subset of the cases could not be staged due to
      processing issues; we thus recommend fixation prior to prosecting.

PMID- 15577673
TI  - What is the best way to assess microsatellite instability status in colorectal
      cancer? Study on a population base of 462 colorectal cancers.
AB  - The assessment of the microsatellite instability (MSI) status in colorectal
      cancers is presently warranted for three reasons: 1) as a screening tool for
      hereditary nonpolyposis colorectal cancer, 2) as a prognostic marker, and 3) as a
      potential predictive factor of chemotherapy response. The aim of this study was
      to evaluate, on a large scale with tissue samples coming from a number of
      different sources, the difficulties met with routine use of immunohistochemistry
      (IHC) and to determine if it really does offer an accurate alternative to PCR
      genotyping. Colorectal carcinomas from 462 consecutive patients resected in
      public or private hospitals were assessed for MSI status by two methods: MSI
      testing (with BAT-26 microsatellite) and IHC detection of hMLH1, hMSH2, and hMSH6
      proteins. Of the 398 cancers tested, immunohistochemistry was noncontributory in
      42 (10.5%), focal in 9 (2.3%), and discordant with the PCR results in 36 (9%).
      For these 87 cases, complementary analyses were performed to explain discrepancy.
      After additional IHC assay with modified processing protocols, 8 cases remained
      noncontributory, 2 focal, and 28 discordant: 18 microsatellite stability IHC/MSI
      PCR and 10 MSI IHC/microsatellite stability PCR. For these discordant cases, we
      performed a multiplex PCR assay on DNA extracted from the frozen sample and BAT
      26 was amplified from DNA extracted from the paraffin blocks used for IHC. Four
      discordant cases were reclassified after PCR multiplex assay (3 as MSI and 1 as
      microsatellite stability). Five other cases displayed intratumoral heterogeneity
      and 19 remained discordant. The discrepancy could be partly explained by variable
      technical protocols of fixation in the different laboratories, leading to
      variations in staining quality and difficulties in IHC interpretation. This
      population-based study is the first one to show that IHC is not sensitive and
      specific enough to be used routinely. Immunohistochemistry analysis of MMR
      proteins must be performed in standardized conditions and interpreted by
      confirmed pathologists. It cannot replace PCR as long as protocols are not
      optimized and harmonized.

PMID- 15577674
TI  - Gastric MALT lymphomas are divided into three groups based on responsiveness to
      Helicobacter Pylori eradication and detection of API2-MALT1 fusion.
AB  - Gastric MALT lymphoma shows unique features including regression by Helicobacter
      pylori eradication and API2-MALT1 fusion. We performed a molecular and
      clinicopathologic study for 115 cases. All eradication-responsive cases were
      devoid of API2-MALT1 fusion. All tumors positive for the fusion and all negative
      for H. pylori infection were nonresponsive to the eradication. Consequently,
      gastric MALT lymphomas were divided into three groups: Eradication-responsive and
      fusion-negative (group A, n = 72), eradication-nonresponsive and fusion-negative
      (group B, n = 22), and eradication-nonresponsive and fusion-positive (group C, n
      = 21). Group A tumors were characterized by low clinical stage and superficial
      gastric wall involvement, and group C tumors by low H. pylori infection rate,
      advanced clinical stage, and nuclear BCL10 expression. All group C tumors showed
      exclusively low-grade histology. Group B tumors, which have not been well
      recognized, frequently showed nodal involvement, deep gastric wall involvement,
      and advanced clinical stage, and sometimes an increased large cell component. A
      multivariate discriminant analysis revealed that responsiveness to the
      eradication could be predicted accurately by negative API2-MALT1 fusion, positive
      H. pylori infection, low clinical stage, and superficial gastric wall invasion,
      the former being the most important factor for the prediction. This 3-group
      categorization may be helpful for a comprehensive understanding of gastric MALT
      lymphoma.

PMID- 15577675
TI  - Serous endometrial cancers that mimic endometrioid adenocarcinomas: a
      clinicopathologic and immunohistochemical study of a group of problematic cases.
AB  - BACKGROUND: Uterine serous carcinomas (USCs) can exhibit an architecturally well
      differentiated tubuloglandular morphology with or without an accompanying
      papillary growth pattern. These features make it difficult to distinguish USCs
      from endometrial endometrioid carcinomas (EECs). Given the aggressive behavior of
      USC, compared with EEC, and differences in management, it is important to
      correctly classify endometrial carcinomas that exhibit a tubuloglandular
      architecture with high nuclear grade. We sought an immunohistochemical panel to
      minimize subjectivity in the distinction of USC from EEC. MATERIALS AND METHODS:
      We identified 8 problematic endometrial cancers, exhibiting a tubuloglandular
      growth pattern and high nuclear grade, whose classification as EEC or USC was
      debated or resulted in disagreement. We selected 13 cases of International
      Federation of Gynecology and Obstetrics (FIGO) grade 2 EEC and 16 cases of USC as
      controls. An immunohistochemical panel, including p53, beta-catenin, cyclin D1,
      estrogen receptor (ER), progesterone receptor (PR), and PTEN, was evaluated.
      RESULTS: As a group, the clinical features and immunoprofile of the study cases
      resembled those of the serous controls. The study cases expressed p53, beta
      catenin, cyclin D1, and ER and PR, and showed loss of PTEN in 75%, 12.5%, 0%,
      37.5%, 37.5%, and 12.5% of cases, respectively. p53, beta-catenin, cyclin D1, ER
      and PR expression, and PTEN loss were seen in 87.5%, 0%, 19%, 31%, 12%, and 0% of
      the serous controls and in 7%, 70%, 54%, 92%, 92%, and 61.5% of the endometrioid
      controls, respectively. The combination of lack of p53 expression, positive PR
      expression, and loss of PTEN best distinguished between EEC and USC using
      discriminant analysis (multivariate P = 0.008, <0.001, and 0.05, respectively).
      CONCLUSION: In endometrial carcinomas exhibiting high nuclear grade and low
      architectural grade, using a panel of immunohistochemical stains may facilitate
      the distinction of USC from EEC. Our clinical and immunohistochemical data also
      support the concept that there is a group of endometrial adenocarcinomas composed
      of tubular glands that are indeed serous carcinomas.

PMID- 15577676
TI  - Paraganglioma-like dermal melanocytic tumor: a unique entity distinct from
      cellular blue nevus, clear cell sarcoma, and cutaneous melanoma.
AB  - We are reporting a previously undescribed primary dermal melanocytic tumor
      identified by reviewing all dermal melanocytic tumors referred in consultation
      that did not qualify histologically as a previously described entity. From these
      cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal
      melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used
      descriptively and does not imply any histogenetic or biologic similarity to true
      paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18
      53 years, mean 35 years; males 2; females 6) which present as a dermal nodule
      (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval
      cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic
      activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy.
      Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and
      microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8)
      and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS
      gene locus, supporting absence of the clear cell sarcoma 12;22 translocation.
      Follow-up information in 8 patients (range, 35-92 months; mean, 54 months)
      indicated that all were alive without disease. PDMT comprises a clinically and
      pathologically unique subtype of dermal melanocytic tumors. Our study suggests a
      benign course, although a lesion of low malignant potential cannot be excluded.

PMID- 15577677
TI  - Tubulolobular carcinoma of the breast: an analysis of 27 cases of a tumor with a
      hybrid morphology and immunoprofile.
AB  - Tubulolobular carcinoma (TLC) is a rare subtype of mammary carcinoma that has
      eluded precise classification, exhibiting features of both ductal and lobular
      differentiation. The clinicopathologic features of 27 cases of TLC were analyzed
      by both hematoxylin and eosin and immunohistochemical stains for E-cadherin and
      34betaE12 (high molecular weight cytokeratin). Five cases of both pure tubular
      and classic lobular carcinoma were included as controls. Patients with TLC ranged
      in age from 43 to 79 years (median, 60 years). Tumor characteristics were as
      follows: size, 0.5 cm to 2.5 cm (median, 1.4 cm); bilaterality, 1 of 27 (4%); and
      multifocality, 5 of 27 (19%). Twenty-two of the 27 cases (81%) contained an in
      situ component: 8 (36%) lobular (LIN); 4 (18%) ductal (DIN); and 10 (46%) mixed.
      All 27 cases were intensely positive (3+) for E-cadherin, a feature of ductal
      differentiation, while 25 of 27 (93%) cases showed variable positivity for
      34betaE12 (1 to 3+), a feature far more common in tumors with lobular
      differentiation. Clinical follow-up was available on 25 of 27 (93%) patients.
      Three of 24 (13%) patients developed axillary lymph node metastases and 1 of 25
      (4%) patients developed a local recurrence over a follow-up period of 2 to 91
      months (median, 39 months). In conclusion, TLCs are a distinct subtype of mammary
      carcinoma with overlapping morphologic features that are mirrored by a hybrid
      immunohistochemical profile. The uniform 3+ expression of E-cadherin in TLC
      supports the ductal differentiation of these tumors, despite a dominant lobular
      growth pattern. The prognosis of these tumors appears to be excellent, especially
      in those cases that are unilateral and less than 2 cm in size.

PMID- 15577678
TI  - The renal sinus is the principal invasive pathway: a prospective study of 100
      renal cell carcinomas.
AB  - A total of 100 renal cell carcinomas were prospectively examined for renal sinus
      invasion, 74 clear cell renal cell carcinomas (CC), 3 renal cell carcinomas,
      unclassified (RUC), 16 papillary renal cell carcinomas (PapC), and 7 chromophobe
      renal cell carcinomas (ChC). Using the 2002 TNM staging formulation, 49 tumors
      were T1, 5 were T2, and 46 were T3 or T4. Renal sinus invasion occurred more
      often than renal capsule invasion. No tumor invaded the capsule that did not also
      invade the sinus. Renal sinus invasion correlated with Fuhrman grade; 17% of
      grades 1/2 tumors invaded the sinus, while 71% of grade 3/4 tumor invaded the
      sinus (P < 0.001). Sinus invasion correlated with tumor type; 2 of 23 PapC and
      ChC invaded the sinus compared with 44 of 77 CC and RUC. Sinus invasion occurred
      in approximately 16% of tumors 1 to 4 cm in size, then abruptly increased for
      larger tumors (P < 0.001). When tumors are staged by the 1997 and 2002 TNM
      formulation, renal sinus invasion upstaged 28% of cases stage T1 or T2 by the
      1997 formulation, to T3 using the 2002 criteria. In conclusion, renal sinus
      invasion is the most common site of extrarenal extension of renal carcinoma and
      correlates with tumor type, grade and size. Appropriate evaluation for sinus
      invasion reduces the incidence of T1b and T2 CC tumors, limiting prognostic
      utility and suggesting reassessment of the T1 and T2 stage designations.

PMID- 15577679
TI  - Distinctive prepubertal vulval fibroma: a hitherto unrecognized mesenchymal tumor
      of prepubertal girls: analysis of 11 cases.
AB  - Eleven cases of a distinctive previously unrecognized mesenchymal tumor that
      arises in the vulvar region in the prepubertal years are described. The tumors
      presented in the vulva (8 cases arising from labia majora) of prepubertal girls
      (range, 4-12 years; median, 8 years). The preoperative diagnoses were labial mass
      or swelling, not otherwise specified in 3 cases, hemangioma in 2 cases, lipoma in
      2 cases, and lymphangioma and Bartholin cyst/lymphedema in 1 case each. The
      tumors were unilateral, ill defined, located in the submucosa or subcutaneous
      tissue, and ranged in size from 2.0 to 8.0 cm in maximum dimension.
      Microscopically, they were poorly marginated, hypocellular neoplasms composed of
      bland spindle-shaped cells in a variably collagenous to edematous or myxoid
      stroma, diffusely infiltrating between preexisting normal vascular, adipose, and
      neural tissues. No cytologic atypia was identified. Mitotic activity was minimal
      with no abnormal mitotic figures. The tumor cells were immunoreactive for CD34 (8
      of 9 cases) but not for smooth muscle actin, desmin, and S-100 protein. Treatment
      was by local excision. From the follow-up data available for 9 patients, 3
      patients showed locally recurrent tumor after 4, 6, and 13 months, respectively,
      of which the second case showed a second recurrence 18 months after the first
      excision. The term "prepubertal vulval fibroma" is suggested because it reflects
      the distinct features of this seemingly unique, previously uncharacterized, site-
      and age-specific mesenchymal tumor.

PMID- 15577680
TI  - ALK-1 expression in inflammatory myofibroblastic tumor of the urinary bladder.
AB  - Inflammatory myofibroblastic tumor (IMT) of the bladder is an uncommon
      myofibroblastic spindle cell proliferation. Because of its cytologic features and
      infiltrative nature, it may be difficult to distinguish histologically from
      sarcomatous proliferations such as sarcomatoid urothelial carcinoma,
      leiomyosarcoma, and embryonal rhabdomyosarcoma. Recently, anaplastic lymphoma
      kinase (ALK) gene translocations or ALK protein expression in IMT has been
      reported, especially in patients of relatively young ages. However, there are
      only a few reports mentioning IMT of the bladder. We sought to determine the
      frequency of ALK expression among IMTs of the urinary bladder. We examined 16
      cases of IMTof the bladder in 14 patients to elucidate the incidence of ALK-1
      expression by immunohistochemistry and its diagnostic usefulness. The age of
      patients with IMT ranged from 18 to 76 years, with an average age of 42.8 years.
      The tumors from 10 of 14 patients (12 of 16 cases) were positive for ALK-1. ALK-1
      positive cases ranged in age from 18 to 73 years (mean, 39.2 years; median, 38
      years) and ALK-1-negative cases from 41 to 76 years (mean, 41.5 years; median,
      44.5 years). Two locally recurrent cases were positive for ALK-1 in both the
      primary and recurrent lesion. ALK-1 immunostaining was detected only in the
      cytoplasm, with granular or subplasmalemmal linear features, suggesting ALK gene
      translocation. ALK-1 immunostaining was also performed in 8 sarcomatoid
      urothelial carcinomas, 5 genitourinary leiomyosarcomas, and 2 stromal tumors of
      uncertain malignant potential of the prostate, all of which were negative. These
      results support that ALK-1 immunostaining is useful to differentiate IMT from
      other malignant spindle cell neoplasms of the bladder. There were no histologic
      differences between ALK-1 positive and negative IMTs.

PMID- 15577681
TI  - Urothelial papilloma of the bladder: a review of 34 de novo cases.
AB  - BACKGROUND: Urothelial papilloma of the bladder is an uncommon entity when using
      restrictive diagnostic criteria. DESIGN: We retrospectively studied 34 patients
      who were diagnosed with urothelial papilloma of the bladder using the criteria of
      the 1998 WHO/ISUP classification system. Six cases were in-house and the
      remaining 28 were referred from other institutions as consults to one of the
      authors. In all cases, the diagnosis of papilloma was the first manifestation of
      urothelial neoplasia. RESULTS: The mean age of the patients at diagnosis was 57.8
      years (range, 23-87 years). The male-to-female ratio was 2.4:1 (24 males and 10
      females). The tumor size averaged 3.3 mm (range, 1-20 mm; median, 2 mm). Simple
      papillary fronds were seen in all cases; in 5 cases the additional finding of
      secondary budding off of small fronds from larger ones was also seen. In all
      cases, the fronds had a round morphology; yet in 4 cases elongated fronds were
      also noted. In 5 cases, dilated lymphatics within the fibrovascular fronds were
      apparent. One case had foamy histiocytes within the fibrovascular stalks. In all
      cases, the lining consisted of normal-appearing urothelium without hyperplasia,
      dysplasia, and/or mitotic figures. Some of the distinctive histologic features
      seen were changes in the umbrella cells: vacuolization (n = 4), prominence with
      cytologic atypia (n = 2), eosinophilic syncytial morphology (n = 1), apocrine
      like morphology (n = 1), and mucinous metaplasia (n = 1). Follow-up was available
      in 26 cases with a mean follow-up for those without evidence of progression of
      28.9 months (range, 3-127 months). Three patients (8.8%) developed recurrent
      papilloma 4, 15, and 18 months after the initial diagnosis of papilloma; 1 of
      these patients also showed progression to noninvasive low-grade urothelial
      carcinoma at the time of recurrence (15 months). Three patients (8.8%) progressed
      to higher-grade disease: 2 to noninvasive low grade urothelial carcinoma (11 and
      15 months after the original diagnosis) and 1 to a papillary urothelial neoplasm
      of low malignant potential at 104 months and a noninvasive low-grade urothelial
      carcinoma at 141 months from the initial diagnosis of papilloma. None of the
      patients demonstrated progression to either lamina propria (T1) or muscularis
      propria (T2) invasion. Two patients died of unrelated causes. None of the
      patients died of bladder cancer. CONCLUSION: Patients with urothelial papillomas
      have a low incidence of recurrence and rarely progress to develop urothelial
      carcinoma. It seems reasonable to avoid labeling these patients as having cancer.
      It remains to be studied whether and when patients with papillomas who have no
      evidence of recurrence or progression no longer need to be followed.

PMID- 15577682
TI  - Consumption of the epidermis: a diagnostic criterion for the differential
      diagnosis of melanoma and Spitz nevus.
AB  - The distinction between melanoma and its most important simulant, Spitz nevus, is
      usually made on microscopically. We point out "consumption of the epidermis"
      (COE) as an additional diagnostic criterion. We defined COE as thinning of the
      epidermis with attenuation of the basal and suprabasal layers and loss of rete
      ridges in areas of direct contact with neoplastic melanocytes. We analyzed 102
      unequivocal melanomas and 125 unequivocal Spitz nevi for the presence of COE. COE
      had not been used in arriving at the diagnosis of these cases because we were
      unaware of the criterion at the time that the cases were first evaluated. COE was
      found in 88 of 102 (86%) of melanomas but only 12 of 125 (9.6%) of Spitz nevi (P
      < 0.001). We then looked for COE in an independent set of 61 ambiguous
      melanocytic lesions with overlapping histopathologic features that could not be
      classified unequivocally as Spitz nevus or melanoma. The cases were analyzed by
      comparative genomic hybridization (CGH) for aberration patterns suggesting a
      benign or a malignant process, based on previous studies. COE was found in only 6
      of 42 (14%) of the ambiguous cases in which CGH suggested a benign process and 14
      of 19 (74%) of the ambiguous cases in which CGH suggested melanoma (P < 0.001).
      Our data suggest that COE is a useful criterion in the evaluation of melanocytic
      neoplasms. Because COE was frequently found at the edges of ulcers in the
      majority of ulcerated melanomas, the thinning of the epidermis in COE may
      represent an early phase of ulceration. This may prove to be important in
      distinguishing ulceration due to an effect of the tumor from ulceration due to
      trauma, which would be expected not to have the same prognostic import. Future
      studies are required to analyze the prognostic value of COE itself.

PMID- 15577683
TI  - Assessment of 142 stellate lesions with imaging features suggestive of radial
      scar discovered during population-based screening for breast cancer.
AB  - Because some lesions diagnosed as radial scars (RS) on core biopsy have been
      found to be malignant on excision, core biopsy has not had an established role in
      the assessment of RS. In our breast cancer-screening program, we have avoided
      core biopsy if RS is suspected on imaging. Recently, two reports have expanded
      the experience with core biopsy of RS, prompting this review of our assessment
      protocols for lesions suspected as being RS. Between January 1996 and January
      2003, stellate lesions with imaging features of RS in which core biopsy was
      omitted because of a presumptive radiologic diagnosis of RS are included.
      Demographic, radiologic, and cytologic data were correlated with the histologic
      findings in the excised specimen. On imaging, 9% (142) of all stellate lesions
      were suspected to be RS. Only 66.2% (94) were confirmed as RS on histology; 38
      cases (28.6%) were carcinomas (36 invasive, 2 in situ) and 7% showed benign
      fibrocystic changes; 87.1% of the carcinomas required further surgery for
      positive margins. Axillary staging was also needed for the invasive cancers.
      Among the histologically proven RS, 28 of 94 (29.8%) showed areas of atypical
      ductal hyperplasia, lobular neoplasia, ductal carcinoma in situ, or invasive
      carcinoma. These proliferations were typically focal and unpredictable and were
      usually completely excised by the initial diagnostic biopsy. Core biopsy would be
      valuable in the assessment of lesions with imaging features suggestive of RS
      since 28.6% of such lesions are indeed carcinomas that mimic RS. Identification
      of these cancers would permit one stage breast and axillary surgery to be
      planned. The policy of mammographic surveillance for lesions with nonmalignant
      core biopsies remains controversial because of the paucity of data. Ongoing
      evaluation is needed as more experience is reported.

PMID- 15577684
TI  - The role of the perifollicular sinus in determining the complex
      immunoarchitecture of angioimmunoblastic T-cell lymphoma.
AB  - The growth of angioimmunoblastic T-cell lymphoma (AIL) in lymph node often
      produces complex patterns of neoplastic T cells and nonneoplastic B cells that
      complicate diagnosis. To understand better how these different patterns of B-cell
      expansion arise, we compared the microanatomic localization of B cells and T
      cells within the follicular, paracortical, and sinusoidal compartments in 30
      patients with AIL (including 10 with multiple sequential samples) with that seen
      in 33 cases of other types of T-cell lymphoma. With early or partial nodal
      involvement in AIL, germinal center B-cell expansions were relatively undisturbed
      and often associated with a variably distended D2-40+ CD31+ perifollicular sinus
      that surrounded most of the follicular compartment. Identifiable tumor T cells
      resided mostly in the paracortex. In later stages of AIL with more complete nodal
      effacement, bcl-6+ follicular B-cell proliferations shifted to distorted FDC
      networks arrayed along patent trabecular sinuses and were more intermixed with
      tumor T cells. In both AIL and other T-cell lymphomas, the density and locations
      of follicular B cells as well as bcl-6-negative monocytoid B cells were largely
      related to the patency of adjacent sinuses, except in Epstein-Barr virus (EBV)+
      and histiocyte-rich B-cell proliferations, which arose in paracortical locations.
      The prominence of the perifollicular sinus in early stages of AIL resembled that
      seen in reactive lymphadenitis during conditions of lymphatic engorgement and
      implicates cytokines within lymph fluid in maintaining both the normal and
      altered germinal center reactions. Patterns of sinus drainage largely explain the
      useful changes in B-cell distribution that occur in nodal T-cell lymphomas and
      represent an important tool in classification and diagnosis of these tumors.

PMID- 15577685
TI  - Benign mechanical transport of breast epithelial cells to sentinel lymph nodes.
AB  - The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant
      epithelial cells is essential to the staging of breast cancer patients. Recently,
      increased attention has focused on the possibility that epithelial cells may
      reach SLNs by benign mechanical means, rather than by metastasis. The purpose of
      this study was to test the hypothesis that pre-SLN biopsy breast massage, which
      we currently use to facilitate the localization of SLNs, might represent a mode
      of benign mechanical transport. We studied 56 patients with invasive and/or in
      situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell
      clusters (< or =0.2 mm in diameter and not associated with features of
      established metastases) detected predominantly in subcapsular sinuses of SLNs on
      hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had
      an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells
      and cell clusters, < or =0.2 mm in size and without features of established
      metastases, occurred more frequently in the SLNs of patients who underwent pre
      SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the
      hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical
      transport of epithelial cells to SLNs.

PMID- 15577686
TI  - Serous carcinoma of the ovary and peritoneum with metastases to the breast and
      axillary lymph nodes: a potential pitfall.
AB  - Metastasis of ovarian or peritoneal serous carcinoma to the breast and/or
      axillary lymph nodes is a rare event. Nevertheless, its recognition and
      distinction from mammary carcinoma are of great clinical importance because the
      treatment and prognosis differ significantly. Eighteen cases of ovarian or
      peritoneal serous carcinoma metastatic to the breast and/or axillary LNs from a
      14-year period (1990-2003) were retrieved from our files. Clinical information
      was obtained from the patients' charts. The age of the patients ranged from 21 to
      67 years (median, 55 years). The primary tumors included 14 ovarian serous
      carcinomas (11 high grade and 3 low grade; 2 of the low-grade tumors presented as
      serous tumors of low malignant potential and recurred as low-grade serous
      carcinoma) and 4 peritoneal serous carcinomas (3 high grade and 1 low grade). Of
      the ovarian neoplasms, 1 was stage I and 10 were stage III tumors; the breast
      and/or axillary lymph node metastases were discovered on average 30 months after
      presentation (range, 7-135 months). Three of the ovarian serous carcinomas were
      stage IV tumors; in 1 case, there were axillary lymph node metastases at initial
      presentation; and in 2 cases, breast and/or axillary lymph node metastases
      developed at 18 and 102 months. Two of the 4 patients with peritoneal serous
      carcinoma presented with stage IV disease, having synchronous breast and axillary
      lymph node metastases; the other 2 patients developed them at 11 and 16 months
      after presentation. Four patients had multiple breast lesions and 8 patients had
      a single metastasis. In 4 cases, the breast metastases were initially interpreted
      as infiltrating ductal carcinoma. The remaining 6 patients had axillary lymph
      node involvement only. The metastases in 17 of the cases had papillary features,
      with psammoma bodies present in 4. Immunoperoxidase studies for GCDFP-15 and WT-1
      were performed in 4 cases; all 4 were positive for WT-1 and negative for GCDFP
      15. Follow-up was available for 17 patients, with 7 patients known to be dead
      from disease (survival range, 2-31 months) after the development of metastatic
      disease to the breast or axillary lymph nodes. Ten patients were alive with
      disease at their last follow-up, which ranged from 1 to 30 months after the
      breast or axillary LN metastasis developed. Metastases to the breast or axillary
      lymph nodes from ovarian and/or peritoneal serous carcinomas are uncommon. Most
      of the patients in whom metastatic disease develops have a known history of
      advanced stage ovarian or peritoneal carcinoma. Breast and/or axillary LN
      involvement at initial presentation can occur but is rare. Differentiation
      between metastatic and primary tumors of the breast is of great importance
      because treatment and prognosis differ significantly. Clinical history, the
      presence of papillary architecture, and WT-1 expression are useful in
      establishing the correct diagnosis.

PMID- 15577687
TI  - Inflammatory myofibroblastic tumor: the continued definition of one type of so
      called inflammatory pseudotumor.

PMID- 15577688
TI  - Malignant perivascular epithelioid cell tumour ("PEComa") of soft tissue: a
      unique case.
AB  - Tumours of perivascular epithelioid cells (PEComas) are being increasingly
      reported at visceral and somatic sites. Both benign and malignant variants have
      been identified, although clinical follow-up is often limited, which prevents
      meaningful predictions of behavior. We report the case of a malignant soft tissue
      PEComa with histologically confirmed regional lymph node metastases and
      radiologically confirmed pulmonary metastases. The light microscopic appearance
      and immunohistochemical profile (HMB-45, smooth muscle actin positive) and
      electron microscopic appearance support perivascular epithelioid cell
      differentiation.

PMID- 15577689
TI  - Chronic antral ulcer associated with gastroduodenal lymphocytic phlebitis.
AB  - Enterocolic lymphocytic phlebitis (ELP) is a rare cause of gastrointestinal
      ischemia. Unlike most vasculitic diseases affecting the gastrointestinal tract,
      ELP involves only the mural and mesenteric veins, which are surrounded by a
      lymphocytic and sometimes granulomatous infiltrate. The mesenteric arterial
      system and the systemic vasculature are characteristically spared. Most patients
      with ELP present with an acute abdomen that resolves following surgical resection
      of the involved bowel. ELP has been reported to involve the small bowel, colon,
      or both, but involvement of the upper gastrointestinal tract has not been
      previously described. Here we report a case of lymphocytic phlebitis that
      affected only the stomach and duodenum. The patient, a 68-year-old man, had a
      nonhealing gastric antral ulcer and underwent hemigastrectomy with vagotomy and
      Billroth II reconstruction. Both the resected stomach and duodenum showed
      characteristic lymphocytic and granulomatous infiltrates that involved the
      submucosal and mural veins, with associated obliteration of vascular lumina; the
      adjacent arteries were completely spared. The patient developed late
      postoperative complications including bile reflux gastritis and erosive
      esophagitis, but he had no recurrence of gastrointestinal ulceration or ischemia
      over a 2-year follow-up. We hypothesize that there may be more cases of upper
      gastrointestinal ELP than are diagnosed as such, in part because the diagnosis
      can be made only on surgical resections specimens.

PMID- 15577690
TI  - What is anaplastic large cell lymphoma?

PMID- 15577693
TI  - Possible precursor of HNPCC-related endometrioid carcinoma of the uterus.

PMID- 15577696
TI  - Preoperative and postoperative anesthetic assessment for pediatric cardiac
      surgery patients.

PMID- 15577697
TI  - Cardiovascular embryology.

PMID- 15577698
TI  - Clinical respiratory physiology of the neonate and infant with congenital heart
      disease.

PMID- 15577699
TI  - Congenital heart diseases with left-to-right shunts.

PMID- 15577700
TI  - Congenital heart diseases with right-to-left shunts.

PMID- 15577701
TI  - Blood gases and pH during hypothermia: the "-stats".

PMID- 15577702
TI  - Aprotinin.

PMID- 15577703
TI  - Inhaled nitric oxide in pediatric cardiac surgery.

PMID- 15577704
TI  - Prescribing--a crucial skill for the palliative care nurse of the future.

PMID- 15577706
TI  - Influence of pain and quality of life on desire for hastened death in patients
      with advanced cancer.
AB  - OBJECTIVE: to assess the relationship between quality of life, pain and desire
      for hastened death in advanced cancer patients. METHODS: 120 Greek patients with
      advanced cancer were interviewed with the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire C30 version 3.0 (EORTC QLQ
      C30), the Greek Brief Pain Inventory (G-BPI), the Greek Hospital Anxiety and
      Depression Scale (G-HADS) and the Greek Schedule of Attitudes toward Hastened
      Death (G-SAHD). RESULTS: statistically significant associations were found
      between total G-SAHD scores and scores for the worst level of pain in the
      previous 24 hours (G-BP13) (r = 0.279, P = 0.002), and between total G-SAHD
      scores and scores for the level of pain relief obtained in the last 24 hours (G
      BP18) (r = -0.326, P = 0.0005). The strongest correlations were found between G
      SADH and emotional functioning (r = 0.569, P<0.0001) and global quality of life
      (r = -0.331, P<0.0001) from EORTC QLQ-C30. In multivariate analyses, emotional
      functioning, social functioning, financial impact, and the interference of pain
      in general activity and mood were significant predictors of G-SAHD (all
      P<0.0001). CONCLUSION: quality of life and pain appeared to have a statistically
      significant relationship with desire for hastened death. Adequate palliative care
      should alleviate pain and the desire for hastened death, improving quality of
      life.

PMID- 15577707
TI  - UK Government responds to Health Committee report.

PMID- 15577708
TI  - Providing spiritual care in end-stage cardiac failure.
AB  - Spiritual care is an integral component of palliative care, whatever a patient's
      diagnosis. This article looks at spiritual care from the perspective of providing
      care for patients living with end-stage heart failure. Such patients face many
      debilitating symptoms and much uncertainty. The issues of how spiritual needs
      should be addressed, what spiritual care entails, and the most appropriate person
      to provide spiritual care are examined.

PMID- 15577709
TI  - Is pain what the patient says it is? Interpreting an account of pain.
AB  - This article discusses the integrated approaches to pain that have developed
      within the pain medicine movement and the hospice and palliative care movement.
      Such approaches blend biomedical, social, emotional and spiritual aspects of the
      pain experience. However, patients and healthcare staff may hold different
      beliefs about pain, such as patients having a medical understanding about pain
      while healthcare practitioners may use concepts such as 'total pain' or
      'psychological pain'. Some of the problems related to interpreting an account of
      pain are discussed and suggestions are made for developing pain assessment,
      education and research.

PMID- 15577710
TI  - Role of a clinical facilitator in introducing an integrated care pathway for the
      care of the dying.
AB  - Integrated care pathways (ICPs) have been developed as a tool for improving end
      of-life care. The Liverpool Care Pathway for the Dying (LCP) is a
      multidisciplinary and evidence-based approach to caring for the dying person. At
      Wythenshawe hospital a clinical facilitator was appointed to facilitate the
      introduction of the LCP. This full-time post, which existed for 18 months,
      involved supporting and educating staff about the pathway. The LCP is now used
      through the general surgical and medical wards and acute and regional coronary
      care units. This article reflects on the different aspects of the role and the
      development of the project.

PMID- 15577711
TI  - Enhancing hospital nurses' knowledge of palliative care: a network nurse
      programme.
AB  - The palliative care network nurse programme was developed to educate and skill
      generalist nurses in the care of the dying patient within the acute hospital
      setting. It developed at the request of nurses who had been involved in the
      piloting of the Liverpool Care of the Dying Pathway. The programme consists of a
      monthly meeting that encompasses an educative component and networking
      opportunities. In a preliminary evaluation of the programme, a questionnaire was
      sent to the network nurses (response rate 80%, n = 33). The nurses reported the
      programme to be beneficial in providing them with increased palliative care
      knowledge. Support and networking opportunities were also identified. This
      article discusses the programme, the evaluation findings and makes suggestions
      for further research.

PMID- 15577712
TI  - Reflection on implementing a care pathway for the last days of life in nursing
      homes in North Wales.

PMID- 15577714
TI  - The rise of the district nursing profession.

PMID- 15577715
TI  - An analysis of clinical risks in vaccine transportation.
AB  - 'Cold chain' transport is an integral part of a system of vaccine transportation
      that assures the potency of vaccines. If the temperature of vaccines is not kept
      between the ranges of 2 and 8 degrees C, this can lead to adverse effects
      especially for the recipients of first time immunization, as no protection is
      offered. This investigation has shown that there is considerable risk of vaccines
      being rendered impotent due to ad hoc collection of vaccines by healthcare
      professionals from pharmacy services, outside of the cold chain transport
      agreement with the vaccine supplier. This is because at present there are no
      guidelines for ad hoc collection of either vaccines or the approved cold chain
      equipment provided to transport the vaccine. The root cause analysis has shown
      that the general practice can manage this risk by making changes to its system
      for vaccine ordering, stock control and maintenance. A number of changes are
      proposed, including the appointment of a vaccine coordinator and the development
      of a protocol for ad hoc collection of vaccines from pharmacy. By focusing on
      improving the quality of the process, the practice can improve the care and
      safety of its immunization programme.

PMID- 15577716
TI  - District nurses: relationships in nurse prescribing.
AB  - Although nurse prescribing has been established in the UK for approximately 8
      years, little is known about the effect this additional role is having on those
      who are involved in its processes. This article reports on the early phrases of
      an ethnographic study which is aiming to discover how prescribing is altering the
      ways in which district nurses relate to general practitioners, pharmacists, other
      community nurses, patients and carers during the experience of nurse prescribing.
      Using qualitative methodology the project has revealed that some relationships
      have improved, while others appear to have deteriorated slightly. Preliminary
      indications are that the introduction of prescribing, along with many other
      centrally driven initiatives, is altering the face of district nursing practice.

PMID- 15577717
TI  - Ileostomy products: an overview of recent developments.
AB  - This article aims to give the reader a brief overview of recent developments in
      appliances for people with an ileostomy. After a brief background, the latest
      products that have been introduced to the market place will be discussed.

PMID- 15577718
TI  - Is that really my job? A guide to job profiling.
AB  - 'Agenda for Change' is fundamental to the NHS modernization agenda. It will lead
      to all non-medical NHS personnel being paid equal salaries for equal work. Key to
      the success of the changes will be the accurate evaluation of each individual's
      job (job profiling), so that people are properly rewarded for their work and
      responsibilities. This article discusses how community nurses can ensure that
      their job profile accurately represents their job, so that 'Agenda for Change'
      will work for them.

PMID- 15577719
TI  - Introducing a health awareness day for the over-75s.
AB  - Working jointly, a community staff nurse from a district nursing team within
      North Bradford Primary Care Trust, and a health visitor (who has a remit to work
      with the elderly) audited their general practice's method of offering all over-75
      year-olds a routine annual health check. They found that the method, level and
      nature of the assessment were not standardized and were organization-led rather
      than patient-led. This group of patients was not receiving the best service that
      could be offered. A more integrated approach was needed, and the idea of a
      'health awareness day' was developed. Evaluation of the day showed that it was
      successful in raising health awareness and in increasing referrals to the GP for
      a variety of problems.

PMID- 15577720
TI  - Screening for dementia in older people.
AB  - Dementia is a growing challenge for health and social care services. Over 750,000
      people are currently living with dementia, a figure predicted to rise to
      approximately 840,000 by 2026. Of these, over 150,000 live alone in the
      community. Early diagnosis of dementia is essential to enable patients and carers
      to make informed choices about their future, and to enable health and carer
      services to plan provision. This article discusses the clinical signs of
      dementia, and the screening tests that can be used to diagnose it. It also
      considers depression, which is often mistaken for dementia, and often occurs
      alongside it. Community nurses are ideally placed to identify the early signs and
      symptoms of dementia, and need to make the most of their position to improve
      support of patients and carers.

PMID- 15577721
TI  - Capillary blood glucose monitoring and its role in diabetes management.
AB  - Capillary blood glucose monitoring (CBGM) plays an important part in achieving
      levels of diabetes control which are associated with reduction in the risk of
      developing diabetes complications. It is vital that the results of CBGM are used
      to adjust treatment to achieve the recommended blood glucose targets. Community
      nurses have a key role in both performing regular and accurate CBGM and in
      teaching people about its use. Equipment used for CBGM, whether by health
      professionals or people with diabetes, needs to be properly maintained so that
      the results are accurate and reliable.

PMID- 15577722
TI  - Ann Keen MP: a district nurse at the heart of government.

PMID- 15577723
TI  - Giving the influenza jab: a review of the law.
AB  - District nursing sister June Harris recently completed the administration of 30
      'flu jabs to frail older residents of a local care home. June encountered a
      number of problems when administering the vaccinations. Relatives of five
      residents with advanced dementia did not want them to have the injection, mainly
      because they had heard that it would give the recipient the 'flu. An 85-year-old
      resident has complained that while she agreed to have a 'flu jab it now appears
      she also had a pneumococcal vaccination as well that no one told her about. More
      seriously, June has recently heard that one resident is in hospital having
      contracted Guillian-Barre Syndrome as a result of the vaccination. June remembers
      that this reluctant resident specifically asked if the 'flu jab would leave her
      paralysed and June had laughingly replied that she had not paralysed anyone to
      date. The residents and their families are now threatening legal action.

PMID- 15577724
TI  - Growing old in the UK.

PMID- 15577726
TI  - [Postpartum hemorrhage: methods used and topics discussed].

PMID- 15577727
TI  - [Postpartum hemorrhage: frequency, consequences in terms of health status, and
      risk factors before delivery].
AB  - In the developing countries, postpartum hemorrhage is the leading cause of
      maternal death and affects approximately 1% of pregnant women. In developed
      countries like ours, maternal mortality is one hundred fold lower but remains the
      cause of maternal death for about 10 women per 100,000 births. In the last
      decade, French confidential inquiries show that the number of maternal deaths by
      postpartum hemorrhage are probably the double of the number in nearby countries,
      whereas hemorrhage should no longer be the leading cause of maternal death in our
      countries. Postpartum hemorrhage is defined as the loss of 500 ml or more blood
      in the 24 hours following delivery (5% of deliveries), but maternal tolerance is
      really threatened starting from 1,000 ml (1% of the women approximately). "Life
      threatening" situations concern approximately one patient in one thousand so that
      obstetricians are rarely faced with this situation. For maternal morbidity or
      mortality, the risk factors of postpartum hemorrhage are nearly the same:
      maternal age, multiple pregnancies, uterine scars, abruptio placentae, cesarean
      section, poor social condition and absence of prenatal care constitute the main
      risk factors of postpartum hemorrhage. Maternal age must be kept in mind because
      it is the most related to mortality by hemorrhage, even if prevention is
      difficult. However, progress in delivery care which are applied to all the
      patients could make it possible to limit the harmful effects of this risk factor.
      A recent study showed that organizational factors also part of the factors of
      risk of maternal morbidity/mortality and could be studied for intervention.

PMID- 15577728
TI  - [Prevention strategies during pregnancy].
AB  - This chapter deals with how to reduce, before delivery, postpartum hemorrhage.
      The strategy is explained for two risk levels, high and low. Means of prevention
      such as: logistical organisation; oral and parenteral iron therapy;
      erythropoietin; autologous blood transfusion; acute hemodilution; transfusion;
      bleeding disorders treatment; hospitalization, tocolysis, choice of mode of
      delivery, caesarean section and anaesthetic techniques for placenta praevia or
      accreta; interest of corticosteroids therapy and magnesium sulfate bleeding risks
      in severe pre-eclampsia, are addressed in turn. The chapter closes with
      professional recommendations ranked according levels of evidence founded in the
      literature.

PMID- 15577729
TI  - [Risk factors of postpartum hemorrhage during labor and clinical and
      pharmacological prevention].
AB  - Prevention of postpartum hemorrhage (PPH) is a major concern in regards to its
      impact on maternal morbidity and mortality. While established risk factors can be
      identified among risk factors of PPH during labor after multivariate analysis:
      prolonged labor, oxytocin stimulation of labor, cesarean section, instrumental
      delivery, genital lacerations and episiotomy, prolonged third stage of labor,
      retained placenta; other risk factors are still uncertain: induction of labor,
      hyperthermia or chorioamniotitis, analgesia or anesthesia, macrosomia, various
      cesarean section techniques. Isolated identified risk factors have a moderate
      incidence on PPH, but their cumulation in one patient is a potential high risk.
      Among active management schemes of third stage of labor for PPH prevention, the
      most efficient technique seems to be direct injection of oxytocin when the baby's
      shoulders are delivered, associated with controlled cord traction. If this
      technique is a must for high-risk patients for PPH, and seems efficient for every
      patient, a correctly performed procedure requires the presence of a competent
      professional in addition to the midwife or obstetrician in charge of delivery,
      and a permanent attention so the length of third stage of labor is shortened. The
      alternative use of prophylactic misoprostol in the third stage of labor is less
      effective than injectable uterotonics in reducing PPH, and is associated with
      more side effects (severe shivering, pyrexia, diarrhea). None of other described
      prophylactic methods have proved efficiency: early suckling, umbilical blood
      drainage, oxytocin umbilical vein injection, among others. A decrease in PPH
      prevalence should be obtained by particular attention on data from the early
      postpartum period, active diffusion of effective prophylactic techniques, and an
      appropriate choice in regards to each delivery unit organization.

PMID- 15577730
TI  - [Initial management of primary postpartum hemorrhage].
AB  - Accurate management of primary postpartum hemorrhage requires perfect knowledge
      of a recent protocol accessible at all times. Staff members and equipment need to
      be adjusted to the emergency situation. The first step is to establish a rapid
      diagnosis. This could be done with collecting bags, placed immediately after the
      birth. Once the diagnosis has been established, it has to be communicated to the
      whole team including obstetricians, midwives and anesthetists. A search for the
      cause of the hemorrhage is premordial. Abdominal uterine palpation confirms the
      diagnosis of uterine atony, the most frequent cause of postpartum hemorrhage. Two
      management schemes are possible depending on whether or not there is retention of
      the placenta. When the placenta is retained, manual removal has to be performed
      to empty the uterine cavity and to rule out uterine rupture. After placental
      delivery, manual control of the uterine cavity is always required. Uterine
      massage has to be performed after the intrauterine manoeuvres and must not be
      stopped too quickly. Rapidly other origins can be excluded: episiotomy or low
      genital tract lacerations requiring rapid repair, coagulation disorders requiring
      specialised care, or hematomas. During the same time, uterotonic drugs have to be
      used. Oxytocin (intravenous injection of 5 to 10 IU) is generally employed.
      Prostaglandins cannot be proposed as publications reporting their efficiency are
      not validated. Meanwhile, the anesthetists will have begun the first measures of
      resuscitation.

PMID- 15577731
TI  - [Anesthesiologists at the initial stage of postpartum hemorrhage].
AB  - Adequate management of postpartum hemorrhage (PPH) requires, after early
      recognition, four components undertaken simultaneously: communication,
      resuscitation, monitoring, investigating the cause of bleeding, arresting the
      bleeding. Early recognition of PPH relies on either a perceived or a quantified
      blood loss of 500-1000 ml and over (using a collecting bag), or the presence of
      clinical signs of shock (hypotension, tachycardia, tachypnea, altered mental
      status). Precise timing of the diagnosis of PPH must be must annotated. Once the
      diagnosis is established, appropriate senior professionals, including the
      anesthesiologist at the early stage, must be called in. The cornerstones of
      initial resuscitation are restoration of blood volume and oxygen carrying
      capacity, achieved, with adequate intravenous access, initially with
      cristalloids, followed by colloids, associated with oxygen by face mask. Initial
      resuscitation is performed and its efficiency is assessed by continuous
      monitoring, hemoglobin bedside tests (Hemocue), full blood count and clotting
      screen. Oxytocine (Syntocinon) efficacy and side-effects are evaluated by
      anesthesiologists. Adequate anesthetic technique must be performed to permit to
      the obstetricians to perform a diagnostic procedure (manual removal of placenta,
      uterine revision), and to most frequently obtain arrest of bleeding. Hemodynamic
      stability is required for loco-regional anesthesia, while on the other hand,
      general anesthesia with crush induction and intubation will be performed.
      Anesthesiologists must anticipate in case of failure of initial measures,
      including in alerting the blood transfusion service and calling for additional
      help.

PMID- 15577732
TI  - [Obstetrical management in the event of persistent or worsening postpartum
      hemorrhage despite initial measures].
AB  - Sulprostone infusion must be started without further delay if the first treatment
      (oxytocin, manual removal of the placenta, uterine revision, vaginal and cervical
      examinations) has been unsuccessful in the first 30 minutes after delivery. In
      France, the use of this treatment has been officially authorized in this
      indication (marketing approval, AMM). Intramuscular and intramyometrial
      injections being contraindicated, sulprostone is administered through continuous
      intravenous infusion. Dosage is 500 microg (one vial) per hour. Starting dose is
      1.7 microg/min (10 ml/h), and can be increased if necessary in steps of 1.7
      microg/min (but not exceeding 8.3 microg./min). The success rate of this
      treatment is linked to the rapidity of its commencement (within 30 min of the
      diagnosis of postpartum hemorrhage). In case of contraindications, since
      postpartum hemorrhage is life-threatening, the benefit-risk ratio needs to be
      estimated. A strict monitoring of cardiovascular parameters is compulsory before
      and after its administration. There is no time limit after which this treatment
      can be considered as ineffective: it depends on the amount of blood lost, the
      patient's clinical state, and on means that have already been used to stop the
      bleeding. However, if after 30 min of sulprostone infusion, there is no
      improvement or if the situation is worse, other therapeutic strategies must be
      considered (e.g., embolization, surgery). The use of intra-rectal misoprostol is
      still under assessment. To date, we have been unable to find studies that justify
      this treatment. Intra-uterine balloon, tube, or mesh packing has been studied in
      a few small series, where it was successful. Use of these strategies must not
      delay the treatment by sulprostone.

PMID- 15577733
TI  - [Anesthesic practices in patients with severe postpartum hemorrhage with
      persistent or worsening bleeding].
AB  - Severe postpartum hemorrhage (PPH) is a rare and critical situation which
      requires fast and well-planned management where close collaboration between
      obstetricians and anesthesiologists is essential. In case of persisting or
      worsening bleeding in spite of initially adequate management, the main goal of
      the anesthesiologist is to maintain hemodynamic stability (fluid resuscitation,
      transfusion, vasoactive drugs) and optimal respiratory state (oxygenation) and to
      correct the frequent clotting disorders, whereas the obstetrician and/or the
      radiologist have to achieve definitive hemostasis. Assessment of the severity of
      PPH is determined from: quantity of blood loss and/or duration of bleeding,
      difficulty in maintaining a correct hemodynamic state in spite of active vascular
      fluid resuscitation, need for vasoactive therapy and transfusion, occurrence and
      worsening of clotting disorders. Continuous drip Sulprostone requires close
      clinical surveillance and continuous monitoring (electrocardiography, non
      invasive blood pressure monitor, pulse oximetry). When this treatment does not
      enable sufficiently rapid control of the bleeding (consensus = within 30
      minutes), invasive therapy (arterial embolization, vascular ligation even
      hysterectomy) should be started promptly. When the bleeding continues despite
      aggressive medical treatments, general anesthesia (even if an epidural catheter
      is already in place) is needed to proceed with the invasive surgical procedure.
      This anaesthesia of a "full stomach" patient justifies a rapid-sequence induction
      with cricoid pressure and intubation. The risk is particularly high in case of
      hemorrhagic shock. Angiographic embolization should be carried out in an
      angiography suite which must be equipped for this kind of situation (anesthesia
      and resuscitation material, adapted monitoring). A member of the anesthesia team
      must be present throughout this procedure. At best, a multidisciplinary team,
      specially trained for this purpose, including obstetrician, anesthesiologist,
      radiologist and biologist should be available. When one or several invasive
      treatments were necessary to control the bleeding, it is recommended to transfer
      the patient to a specialized unit (intensive care unit or recovery room).

PMID- 15577734
TI  - [Modalities for maternal transfer in the event of postpartum hemorrhage].
AB  - In the event of a postpartum bleeding, the decision to undertake a medical
      transfer should be made in concertation by the different physicians involved: the
      hospital that requests the transfer, the Emergency Medical and Mobile Service,
      the receiver. The choice of a health care provider depends on the health care
      facilities, the possibility to admit the patient and the time parameter. A
      transfer is contraindicated for patients with an unstable hemodynamic state and
      when hemostatic surgery is essential. During transportation, only cardiopulmonary
      techniques are allowed. Patient monitoring, anesthesia and resuscitation during
      the embolization process should be done by the critical care team in the hospital
      and not by emergency physicians and nurses. As a precaution, after the team has
      assessed the situation locally and before it worsens, a transfer, including intra
      uterine transfer, should be discussed and completed toward a health care facility
      equipped to provide rapid and varied emergency care. When postpartum bleeding
      occurs after an unexpected birth out of the hospital, rapid medical
      transportation toward a health care facility equipped to provide varied emergency
      care is required. The emergency care unit should be informed prior to the
      transfer.

PMID- 15577735
TI  - [Management of life-threatening postpartum hemorrhage: indications and technique
      of arterial embolization].
AB  - Pluridisciplinary management of women with postpartum hemorrhage is mandatory in
      order to precisely assess initial seriousness, to maintain hemodynamic parameters
      and to confirm the cause of bleeding. Embolization should be offered only after
      exploration of the uterine cavity, inspection of the vagina, cervix and perineum
      and failure of uterotonic drugs. Embolization should be carried out in an
      angiography suite under constant monitoring of the patient by the
      anesthesiologist. Indications to perform arterial embolization include uterine
      atony particularly following a vaginal delivery, cervico-uterine hemorrhage,
      cervicovaginal lacerations (previously repaired or if surgical repair has failed)
      and vaginal thrombus, particularly in case of associated coagulopathy. Arterial
      embolization is effective in about 85% of cases. Placenta acccreta can also be
      successfully managed with arterial embolization as an alternative to
      hysterectomy. Unilateral femoral approach allows selective study of both internal
      iliac arteries and branches. Selective embolization of both uterine arteries
      should be ideally performed. In case of spasm or difficult catheterization,
      embolization of the anterior division of both internal iliac arteries should be
      considered. In case of bleeding from the cervico-vaginal region, selective
      evaluation and embolization of cervicovaginal branches should be performed. In
      case of failure or recurrence of bleeding, ovarian and round ligament arteries
      should be evaluated. In most cases, resorbable gelatin sponge pledgets should be
      used to perform embolization. The use of microcatheters and non resorbable
      embolization agents should be considered by trained interventional radiologists
      in case of placenta accreta or vascular lesions. After embolization, the patient
      should be transferred to the intensive care unit for further observation in order
      to offer emergent surgical procedure or another session of embolization in case
      of recurrence of bleeding.

PMID- 15577736
TI  - [Surgical management of primary postpartum hemorrhage].
AB  - Despite the development of medical, obstetrical and arterial embolization
      techniques to control acute postpartum hemorrhage, familiarity with surgical
      procedures is essential. They may be the ultimate available option in order to
      obtain hemostasis. Conservative techniques consist of arterial ligations and
      uterine compression sutures that preserve the reproductive future and may be
      combined together. Radical options include hysterectomy which may be total or sub
      total. To date, there are no comparative trials assessing the superiority of a
      given surgical option. In this review, the main surgical interventions are
      described and a practical stepwise approach is discussed according to the
      etiology, based on a professional consensus work-shop. Surgical management must
      be timely triggered after failure of first line treatments and integrated in a
      global strategy aimed to cease hemorrhage. It should be adapted to the available
      local health resources and in compliance with the various members of the medical
      staff.

PMID- 15577737
TI  - [Management of blood products in the event of postpartum hemorrhage].
AB  - Transfusion during the treatment of postpartum hemorrhages is rare. It always
      occurs in complex situations: failure of the initial manipulations or cataclysmic
      bleeding. Its management is multidisciplinary and should aim at obtaining blood
      products within thirty minutes while preventing any risk of alloimmunization
      detrimental to the obstetrical future of the patient. Upstream process management
      is essential. The following points will be described: Within the legal bounds,
      the different options for blood products supply; the best practices procedures
      that every maternity hospital should set up and formalize; the immunohematologic
      documents to be used for transfusions, their validity and the criteria for the
      prescription of irregular antibody testing; the rules for antenatal management to
      anticipate the transfusion difficulties; the blood products available and their
      constraints of use to optimize the prescription. Effective management can be
      achieved only through the strict respect of procedures at every stage. These
      procedures should be written in conjunction with all actors, issued and regularly
      assessed.

PMID- 15577738
TI  - [Guidelines for postpartum hemorrhage].

PMID- 15577739
TI  - Factors underlying chronic inflammation in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA)is a debilitating chronic inflammatory disease whose
      characteristic pathology includes swollen, painful, and deformed joints. In
      recent decades, both clinical and basic scientific research have tried to
      determine the factors involved in the pathogenesis of this common disease.
      Although the cause of RA is still unknown, several factors that contribute to RA
      have been identified. Among these are the discoveries of: susceptibility genes,
      disease-causing immune cells, and cytokine and signal transduction networks
      involved in promoting persistence of inflammation. Various therapeutic
      strategies, including anti-tumor necrosis factor therapy, have been developed to
      target one or more of these factors. Although none of these therapeutic
      strategies can actually cure the disease, some of these novel agents have proven
      to be more effective than others. This implies that the success of a therapy is
      very much dependent on the therapeutic targets chosen. Therefore, improved
      understanding of the cellular and molecular events occurring in the rheumatoid
      joint during the pathogenesis of the disease is particularly important if we are
      to better combined therapeutic strategies. In this article we summarize current
      understanding of the factors that contribute to disease pathogenesis in RA and
      identify cellular and molecular events that could drive the development of the
      disease and represent potential new therapeutic targets.

PMID- 15577740
TI  - Macrophage migration inhibitory factor and its role in autoimmune diseases.
AB  - After several decades of research into the macrophage migration inhibitory factor
      (MIF), its diverse actions in the immune system are yet to be fully revealed.
      What has become clear is that MIF plays an important role in both innate and
      adaptive immunity. However, while several pathways mediating the function of MIF
      in the immune system have been established, its role in pathogenic states such as
      autoimmune diseases has remained unresolved. MIF has been implicated in different
      autoimmune diseases, including rheumatoid arthritis, glomerulonephritis, and
      multiple sclerosis, but knowledge about the underlying cellular and molecular
      mechanisms is just emerging. However, overall it appears that the inhibition of
      its proinflammatory action is likely to be a successful new therapeutic strategy
      for some autoimmune diseases, possibly by reducing the need for steroids. As more
      aspects of the role of this cytokine in the pathogenesis of autoimmune diseases
      are elucidated, better strategies to target it therapeutically can be expected.

PMID- 15577741
TI  - RNA interference:a potential novel therapeutic combating HIV-1 in the central
      nervous system.
AB  - RNA interference (RNAi)is a conserved process by which eukaryotic cells protect
      their genomes utilizing small, double-stranded RNAs to degrade target RNAs. This
      occurs in a sequence-specific manner and is different from the interferon effect
      of larger double stranded RNAs. Post-transcriptional gene silencing by these
      nucleic acids can lead to degradation of either cellular or viral RNAs. It has
      been recently shown that double stranded, small interfering RNAs (siRNAs)of 21 to
      25 nucleotides can be transfected into relevant cells to target specific RNAs. In
      addition, utilizing hairpin motifs, siRNAs can be expressed intracellularly using
      molecular therapeutic vectors. This potent approach has been utilized to both
      inhibit pathogens, including viruses, as well as to dissect cellular molecular
      mechanisms via a potent knockout effect. At this time in the HIV-1-pandemic,one
      of the remaining, most enigmatic, and still vitally important areas of HIV-1
      pathogenesis occurs in the central nervous system (CNS).HIV-1-induced
      encephalopathy remains difficult to treat in the developing world and in parts of
      the developed world, even in the era of highly active anti-retroviral therapy. As
      such, novel approaches which could lead to intracellular immunization, and life
      long resistance against HIV-1 encephalopathy would be of important impact
      worldwide. Thus, we now seek to combine our background in molecular therapeutics
      and RNAi with our long-standing interest in HIV-1 neuropathogenesis to target the
      CNS using siRNAs.

PMID- 15577742
TI  - The influence of aging in one tauopathy: Alzheimer 's disease.
AB  - In this short review, the link between aging and the onset of Alzheimer 's
      disease is discussed. It has been widely suggested that aging is the greatest
      risk factor for Alzheimer 's disease,in which a failure in the insulin signal
      transduction pathway could occur with age and, thereby, the assembly of senile
      plaques and neurofibrillary tangles (two aberrant structures present in Alzheimer
      's disease)could be promoted. The main component of neurofibrillary tangles is
      the microtubule-associated protein tau, and the assembly of tau protein appears
      to occur after its modification by phosphorylation. In this phosphorylation, some
      protein kinases related to the insulin-transduction pathway could play a role.

PMID- 15577743
TI  - Fatty acid synthase-catalyzed de novo fatty acid biosynthesis: from anabolic
      energy-storage pathway in normal tissues to jack-of-all-trades in cancer cells.
AB  - In 1994, Kuhajda and colleagues unambiguously identified the oncogenic antigen
      519, a prognostic molecule found in breast cancer patients with markedly worsened
      prognosis, as fatty acid synthase (FAS),the key enzyme for the de novo fatty acid
      biosynthesis. It now appears that human carcinomas and their pre-neoplastic
      lesions constitutively over express FAS and undergo significant endogenous fatty
      acid biosynthesis. Moreover, FAS blockade specifically induces apoptotic cancer
      cell death and prolongs survival of cancer xenograft hosts. Therefore, FAS
      signaling seems to play a central role in the maintenance of the malignant
      phenotype by enhancing cancer cell survival and proliferation. This review
      documents the rapidly changing perspectives on the function of FAS in cancer
      biology. First, we describe molecular mechanism by which aberrant transduction
      cascades driven by oncogenic changes subvert the down-regulatory effects of
      dietary fatty acids, resulting in tumor-associated FAS insensitivity to
      nutritional signals. Second, we speculate von the putative function that hypoxia
      can play as the epigenetic factor that triggers and maintains FAS overexpression
      in cancer cells by inducing changes in gene expression and in metabolism for
      survival. Third, we explore the role that FAS exhibits in cancer evolution by
      specifically regulating cancer-related proteins such as Her-2/neu oncogene and
      estrogen receptor. Finally, we reveal previously unrecognized functions of FAS on
      the response of cancer cells to chemo-,endocrine-,and immuno therapies. These
      findings, all together, should ultimately enhance our understanding of how FAS
      dependent endogenous fatty acid metabolism, once considered a minor anabolic
      energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer
      cells.

PMID- 15577744
TI  - Recent controversy surrounding lipid rafts.
AB  - Lipid rafts (LRs)are highly enriched in glycosphingolipids, sphingomyelins, and
      cholesterol membrane microdomains, existing in a liquid-ordered phase of the
      plasma membrane. In the literature, LRs are also known as detergent-insoluble
      membranes, detergent-resistant membranes, glycosphingolipids-enriched membranes,
      detergent-insoluble glycolipid-rich membranes, and Triton-insoluble floating
      fractions. These properties enabled their separation from the rest of the
      phospholipid bilayer, providing new insight into the structure of the plasma
      membrane, which until then was believed to represent a two-dimensional liquid
      structure with proteins uniformly solubilized in the lipid solvent. Although
      there have been many articles concerning LRs, there is still controversy about
      their existence in the natural state, their size, definition, and function.
      Different techniques have been developed to visualize LRs in living cells, but
      the results are contradictory. In this minireview, some recent papers concerning
      LRs, their existence in vivo, their dynamics, size, methods of isolation, and
      their association with different proteins are discussed.

PMID- 15577745
TI  - Concentration of TBA-reactive substances in type II pneumocytes exposed to
      oxidative stress.
AB  - INTRODUCTION: Oxidative lung damage may be associated with the destruction of
      alveolar cells. Type II alveolar epithelial cells (AECs),as progenitors of type I
      cells, are indispensable for the renovation of alveolar structure after lung
      injury. Extensive damage to type II cells could be responsible for unfavorable
      outcome. However, the susceptibility of type II AECs to oxidative stress is
      unclear. MATERIAL/METHODS: We investigated the susceptibility of freshly isolated
      and cultured rat type II AECs to oxidative stress (H2O2 and Fe2+). Thiobarbituric
      acid reactive substances (TBARS)were measured as indices of lipid peroxidation
      and cytotoxicity was estimated by the MTT test. Aminotriazol (ATZ), an inhibitor
      of intracellular catalase, was used to estimate the protective role of catalase.
      RESULTS: TBARS concentration increased significantly in freshly isolated, oxidant
      exposed cells (4.0 +/-1.3 vs.8.3 +/-2.2 nmol/g protein, p=0.0313)and
      insignificantly in cultured cells (1.7 +/-0.4 vs.4.4 +/-1.7 nmol/g protein).ATZ
      was toxic even to cells not exposed to oxidants. Inhibition of catalase in cells
      exposed to oxidants resulted in an insignificant increase in TBARs:4.5 +/-1.5
      vs.16.2 +/-3.9 nmol/g protein, p=0.0625,and 4.0 +/-0.8 vs.7.6 +/-4.0 for freshly
      isolated and cultured cells, respectively. Oxidative stress itself did not
      increase cytotoxicity. CONCLUSIONS: Type II AECs are not resistant to oxidative
      stress. We cannot, however, explain why cells with evidence of lipid peroxidation
      do not show increased cytotoxicity. The toxicity of ATZ is not related to
      oxidative cell damage. In cells exposed to oxidants, TBARS may fur-ther increase
      when catalase is inhibited, which suggests an important protective role for
      catalase.

PMID- 15577746
TI  - The search for a genetic defect in Polish patients with chronic granulomatous
      disease.
AB  - INTRODUCTION: Chronic granulomatous disease (CGD)is a rare inherited disorder in
      which phagocytic cells are unable to generate superoxide anions. Patients with
      CGD are predisposed to recurrent bacterial and fungal infections because the
      superoxide-generating NADPH oxidase activity is needed for efficient killing of
      microbes. Among the at least 5 subunits cre-ating a functional NADPH oxidase, a
      molecular defect located in any of the gp91phox, p22phox, p47phox, or p67phox
      subunits may cause CGD. MATERIAL/METHODS: In this study,8 patients were diagnosed
      with CGD on the basis of clinical findings and absence of nitroblue tetrazolium
      reduction in phagocytes. Southern blot analysis, GeneScan, and direct sequencing
      were performed to define particular DNA mutations. RESULTS: Among 6 X-linked CGD
      (X-CGD)patients, 4 different mutations were identified in the X-linked CYBB gene
      (encoding gp91phox)by direct sequencing. A novel missense mutation, located in
      the NADPH-binding region of gp91phox,was found in 2 brothers. One frameshift
      1578delA, one splicing 252G->A mutation, and one partial gene deletion were also
      identified. The molecular defect in the NCF1 gene (encoding p47phox)was
      established in 2 patients. One was DeltaGT/DeltaGT homozygote, the other carried,
      besides this GT deletion on one allele, a unique Phe118stop mutation on the
      other. CONCLUSIONS: In general, the X-CGD patients within the group followed a
      more severe clinical course than the patients with an NCF1 defect. However, the
      lack of a straightforward genotype phenotype correlation indicates that the
      clinical severity of CGD depends also on other antimicrobial host-defense
      systems.

PMID- 15577747
TI  - Temperature can prime human peripheral blood neutrophils in a p38MAPKalpha
      dependent manner.
AB  - INTRODUCTION: Previous ex vivo experiments by others suggest that elevated body
      temperature can prime the respiratory burst of human neutrophils. The mechanism
      of the priming phenomenon induced by temperature has not been addressed so far.
      Furthermore, the priming temperature range was not defined. MATERIAL/METHODS: In
      the present study we explored ,under in vitro conditions, the influence of
      febrile-range temperatures on reactive oxygen species (ROS)generation by human
      peripheral blood neutrophils. ROS production was measured using whole.blood
      luminol-dependent chemiluminescence. Two elements of signal transduction
      pathways, calcium and p38 mitogen.activated protein kinase alpha (p38MAPKalpha)
      ,frequently underlying neutrophil priming were also examined. Calcium levels in
      the cytosol of resting and fMLP. stimulated isolated neutrophils were measured
      with the Fura-2AM spectrofluorimetric method. The activity of p38MAPKalpha was
      assessed indirectly with a specific inhibitor of the kinase, SB 203580. RESULTS:
      The study revealed a priming effect at 38 degrees C toward human peripheral blood
      neutrophil ROS production. Any concomitant effect on calcium response was not
      observed. Instead, experiments with SB 203580,a specific inhibitor of
      p38MAPKalpha, pointed to an increased activity of the kinase as a molecular
      background of temperature-induced priming. However, the priming effect of
      temperature was confined to 38 degrees C, while higher temperatures proved to
      exert no effect (39 and 40 degrees C)or even inhibited ROS generation by
      neutrophils (43 degrees C). CONCLUSIONS: Our study suggests a heterogeneous
      influence of temperature on human neutrophil functioning, including the priming
      of the cells by a low-febrile-range temperature. It also suggests a p38MAPKalpha
      dependent molecular background of the priming phenomenon.

PMID- 15577748
TI  - [The genetic basis of childhood nephrotic syndrome].
AB  - Great progress has been made of late in understanding the mechanisms of
      proteinuria, the structure and function of the slit diaphragm, and the genetic
      background of congenital nephrotic syndromes in new borns and infants. This paper
      presents recent achievements of molecular genetics in unraveling the causes of
      inherited disorders, e.g. Finnish-type nephrotic, Denys-Drash and Frasier's
      syndromes, as well as sporadic focal-segmental glomerulosclerosis. A change in
      the routine policy used in evaluating the causes of childhood nephrotic syndrome
      is discussed.

PMID- 15577749
TI  - [Neuroprotective role of PACAP, VIP, and PHI in the central nervous system].
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal
      peptide (VIP), and peptide histidine-isoleucine (PHI) belong to a structurally
      related family of polypeptides present in many regions of the central and
      peripheral nervous system. The neuroprotective potential of PACAP, VIP, and PHI
      has become a matter of intensive investigations in many animal models. In vitro
      studies revealed that PACAP protects neurons against apoptosis occurring
      naturally during CNS development and apoptosis induced by a series of
      neurotoxins, such as ethanol, hydrogen peroxide (H2O2), prion protein, beta
      amyloid, HIV envelope glycoprotein (gp120), potassium ion deficit, and high
      glutamate concentrations. Similarly, in vivo investigations conducted in models
      of ischemia and Parkinson's disease confirmed the neuroprotective properties of
      PACAP. It was revealed that the anti-apoptotic action of PACAP can be directly
      associated with the activation of signal transduction pathways preventing
      apoptosis in neurons or involve glial cells capable of releasing other
      neuroprotective factors affecting neurons. In contrast to PACAP, the
      neuroprotective action of VIP depends mainly on stimulation of astrocytes to
      produce and secrete factors of extremely high neuroprotective potential,
      including activity-dependent neurotrophic factor (ADNF) and activity-dependent
      neuroprotective protein (ADNP). It was shown that ADNF and ADNP, as well as their
      shortened derivatives ADNF-9 and NAP, prevent neurons from electrical blockade,
      excitotoxicity, apoE deficiency, glucose deficit, ischemia, toxic action of
      ethanol, beta-amyloid, and gp120. The neuroprotective potential of PHI has not
      been as thoroughly investigated yet, but recent data have confirmed that this
      peptide can also function as a neuroprotectant. It is thought that PACAP, VIP,
      and possibly PHI may serve as a goal of modern therapeutic strategies in various
      neurodegenerative disorders.

PMID- 15577750
TI  - [Complex forms of immune insufficiency to some cytokines (TNF-alpha, interferons)
      in colorectal cancers as exemplified by the COLO 205 cell line. Mechanism of
      resistance with special reference to signaling proteins and cytokines].
AB  - Since colorectal cancer cells are characterized by both high immune- and
      multidrug-resistance, investigations concerning the search for cytokines,
      especially interferons, which would delete cancer cells have prospects of success
      only if cancer cells became sensitive to such treatment. The prerequisite for
      successful treatment is to discover how the immune system kills colorectal cancer
      cells. In this article we focus our attention on signal transduction pathways in
      colorectal cancer cells, which are characterized by a variety of mechanisms that
      enable them to survive the hostile microenvironment created by immune system
      attack. Knowledge relevant to cancer cell immunity to defense mechanisms is
      crucial for the prospects of cytokine-supportet therapy. A case in point is the
      human colorectal cancer cell line COLO 205, which is not affected by individual
      cytokines, although it becomes vulnerable to combined treatment with some of
      them. It is not clear what factors make COLO 205 cells resistant to cytotoxins,
      however; it seems plausible to point to the complex signaling pathways, and STAT
      proteins in particular. Another feature of COLO 205 cells avoiding cytokine
      mediated death signals is the reverse signaling causing activated macrophages to
      become dormant in response to soluble TNF-alpha receptors (sTNF-alpha R1, sTNF
      alpha R2). Similarly, COLO 205 cells respond to the proinflammatory cytokine IL-6
      released by activated macrophages. Cancer cells release anti-inflammatory
      cytokine IL-10, which ceases the action of PMNCs. It should be stressed that
      STATs mediate and/or activate the transcription of several genes indispensable
      for cell death. Cancer cells isolated from large bowel tumors express elevated
      constitutive activity of STATs inhibitors leading to antiapoptosis.
      Correspondingly, the increased survival rates of these cells could be attributed
      to accelerated actions of the PI-3K/Akt, cPKC/Raf1/ERK, NF- kappaB/JNK, or
      Jak/STAT cascades. Finally, an uncertainty in large bowel cancer cells is whether
      STATs might redirect the cytokine signal from cell deletion to cell survival.

PMID- 15577751
TI  - [Trends in nonsteroidal anti-inflammatory drug development and application].
AB  - Since the synthesis of salicylic acid, research into the synthesis of new
      nonsteroidal anti-inflammatory drugs (NSAIDs) has continued in two directions:
      drugs with higher anti-inflammatory activity and those causing less adverse side
      effects. Several very potent classic, non-selective NSAIDs were already available
      in the 1970's, but problems with their toxicity, especially gastro- and
      nephrotoxicity, have remained unsolved. The discovery of two cyclooxygenase (COX)
      isoforms, COX-1 and COX-2, was a breakthrough that led to obtaining the so-called
      coxibs, which selectively inhibit COX-2. This property makes this kind of NSAID
      less gastrotoxic than classic, non-selective NSAIDs. Other strategies to reduce
      the toxic effects of NSAIDs were their applications as prodrugs or purified
      enantiomers. The latest are the synthesis of classic NSAIDs combined with a
      chemical group that serves as a nitric oxide donor or the synthesis of double
      cyclooxygenase/5-lipoxygenase inhibitors. Simple inhibition of prostaglandin (PG)
      synthesis cannot completely stop the inflammatory process. Therefore new agents
      are tested for their influence on many other elements of the mechanism of
      inflammation, e.g. the formation of inflammatory cytokines, free radicals and
      biogenic amines by the stimulated inflammatory cells. Such pleiotropic activity
      of an NSAID might increase its anti-inflammatory action.NSAIDs are widely used
      not only for their anti-inflammatory, but also analgesic, antipyretic, and (as in
      case of aspirin) anti-coagulating activity. Results of the latest studies suggest
      that NSAIDs prevent colorectal cancer and may protect against the development of
      Alzheimer's disease as well. Precise studies of NSAIDs' mechanism of action (e.g.
      research on the genetic conditions of NSAID metabolism, the discovery of COX-3,
      studies on microsomal PGE synthase or PG receptors) will probably enable the
      synthesis of other more selectively acting compounds.

PMID- 15577752
TI  - Treating opportunistic infections among HIV-exposed and infected children:
      recommendations from CDC, the National Institutes of Health, and the Infectious
      Diseases Society of America.
AB  - In 2001, CDC, the National Institutes of Health, and the Infectious Diseases
      Society of America convened a working group to develop guidelines for therapy of
      human immunodeficiency virus (HIV)-associated opportunistic infections to serve
      as a companion to the Guidelines for Prevention of Opportunistic Infections Among
      HIV-Infected Persons. In recognition of unique considerations related to HIV
      infection among infants, children, and adolescents, a separate pediatric working
      group was established. Because HIV-infected women coinfected with opportunistic
      pathogens might be more likely to transmit these infections to their infants than
      women without HIV infection, guidelines for treating opportunistic pathogens
      among children should consider treatment of congentially acquired infections
      among both HIV-exposed but uninfected children and those with HIV infection. In
      addition, the natural history of opportunistic infections among HIV-infected
      children might differ from that among adults. Compared with opportunistic
      infections among HIV-infected adults, which are often caused by reactivation of
      pathogens acquired before HIV infection when host immunity was intact,
      opportunistic infections among children often reflect primary acquisition of the
      pathogen and, among children with perinatal HIV infection, infection acquired
      after HIV infection has been established and begun to compromise an already
      immature immune system. Laboratory diagnosis of opportunistic infections can be
      more difficult with children. Finally, treatment recommendations should consider
      differences between adults and children in terms of drug pharmacokinetics,
      dosing, formulations, administration, and toxicities. This report focuses on
      treatment of opportunistic infections that are common in HIV-exposed and infected
      infants, children, and adolescents in the United States.

PMID- 15577753
TI  - Rickettsialpox: report of three cases and a review.
AB  - Rickettsialpox is a rare mite-borne rickettsiosis that is encountered in urban
      populations in the eastern United States and throughout the world. It is
      characterized clinically by an eschar, fever, and a papulovesicular eruption.
      Both of these cutaneous manifestations may be mimicked by infectious diseases
      that have been designated as bioterrorist agents by the United States Centers for
      Diseases Control and Prevention: the former by anthrax, and the latter by
      smallpox. It is thus important for clinicians to be familiar with rickettsialpox.
      We report 3 cases and review the epidemiology, clinical and laboratory findings,
      differential diagnosis, and management of this disease.

PMID- 15577754
TI  - Treatment of eosinophilic pustular folliculitis with tacrolimus ointment.
AB  - We describe a patient with eosinophilic pustular folliculitis who partially
      responded to oral indomethacin, but intermittently experienced new eosinophilic
      pustular folliculitis lesions. Treatment with tacrolimus ointment 0.1% resulted
      in the rapid improvement of each recurred lesion and allowed withdrawal of
      indomethacin. To our knowledge, this is the first report of the use of topical
      tacrolimus in the treatment of eosinophilic pustular folliculitis.

PMID- 15577755
TI  - Primary carcinoid tumor of the skin.
AB  - We describe the case of a 64-year-old man with a cutaneous carcinoid tumor.
      Clinical investigation and diagnostic studies failed to reveal an internal
      primary tumor. Five cases of primary cutaneous carcinoid tumor have been reported
      in the literature. Interestingly, our patient had coexisting lichen planus, which
      has been reported previously in association with carcinoid.

PMID- 15577756
TI  - Hypertrichosis of the eyelashes caused by bimatoprost.
AB  - The phenyl-substituted analog of prostaglandin F 2alpha , latanoprost (Xalatan;
      Pfizer, Inc, New York, NY) is an intraocular pressure (IOP)-lowering drug for use
      in patients with glaucoma and ocular hypertension. Latanoprost has been shown to
      stimulate eyelash hypertrichosis and has recently been proposed as a possible
      treatment for alopecia areata involving the eyelashes. We report a case of
      hypertrichosis of the eyelashes caused by the prostamide bimatoprost (Lumigan;
      Allergan, Inc, Irvine, Calif), a new IOP-lowering drug.

PMID- 15577757
TI  - Acute lymphoblastic leukemia presenting with urticarial plaques and
      hypereosinophilia in a child.
AB  - Our report describes a previously healthy 10-year-old female who was seen for
      urticarial plaques and mild loss of appetite. An initial laboratory workup
      revealed an elevated leukocyte count of 30,000/microL and a peripheral eosinophil
      count of 22,500/microL. A skin biopsy showed a marked hypersensitivity tissue
      response with abundant eosinophils. Further investigation of her peripheral
      eosinophilia uncovered Giardia lamblia in a stool sample. Despite treatment with
      the anti-parasitic agent furazolidone, the patient's urticarial plaques,
      leukocyte count, and peripheral eosinophil count remained unchanged. A bone
      marrow biopsy confirmed a diagnosis of acute lymphoblastic leukemia (ALL). ALL
      with hypereosinophilia (ALL/Eo) represents a rare and distinct subset of ALL,
      with more than 30 cases documented in the literature. Our discussion summarizes
      the clinical aspects of this disease and reviews the reported dermatological
      manifestations of ALL/Eo.

PMID- 15577758
TI  - Superficial morphea in a man.
AB  - Superficial morphea is a recently described condition with distinct clinical and
      histologic features that distinguish it from classic morphea. To date this
      disease has been reported only in females. We present a report of this condition
      in a man.

PMID- 15577759
TI  - Poison ivy: an underreported cause of erythema multiforme.
AB  - The relationship between herpes simplex virus (HSV) and erythema multiforme (EM)
      has been well described. Many authors contend that EM (excluding Stevens-Johnson
      syndrome and toxic epidermal necrolysis) occurs almost exclusively as a response
      to HSV infection. During the past year, however, we have observed several cases
      of EM complicating severe Rhus allergic contact dermatitis. Although this
      association has been previously documented, the paucity of cases in the
      literature, along with our experience, suggests that this is an underreported
      phenomenon. We describe 4 of our cases.

PMID- 15577760
TI  - Tumid lupus erythematosus occurring following highly active antiretroviral
      therapy for HIV infection: a manifestation of immune restoration.
AB  - Tumid lupus erythematosus (LE) is a relatively rare and only recently recognized
      subset of chronic cutaneous lupus. We report a case occurring in a male with HIV
      infection whereby his rash was only unmasked by immune restoration following
      highly active antiretroviral therapy (HAART). The phenomenon of latent
      inflammatory or autoimmune disease appearing following HAART is now recognized as
      the "immune restoration syndrome" and tumid LE has not been reported in this
      setting previously. Fortunately this variant of lupus does not result in scarring
      and is responsive to anti-malarials, allowing continuation of HAART in this
      patient.

PMID- 15577761
TI  - Primary cutaneous extraskeletal osteosarcoma under a previous electrodessicated
      actinic keratosis.
AB  - Extraskeletal osteosarcoma represents approximately 1% of soft tissue sarcomas
      and approximately 4% of all osteosarcomas. It is therefore much rarer than
      osteosarcoma arising primarily in bone. Skin as a primary site has seldom been
      reported. This report describes an extraskeletal osteosarcoma of the skin under a
      previously electrodessicated actinic keratosis.

PMID- 15577762
TI  - Kaposi's varicelliform eruption in association with rosacea.
AB  - Kaposi's varicelliform eruption is characterized by disseminated vesiculopustules
      and erosions caused by a herpes virus infection superimposed on a pre-existing
      dermatosis. The eruption usually occurs in individuals with atopic dermatitis or
      other pre-existing dermatosis such as Darier's disease, pemphigus foliaceus,
      mycosis fungoides, Sezary syndrome, benign familial pemphigus, ichthyosis
      vulgaris, second-degree burns, multiple myeloma, and Grover's disease. We report
      here a new case of Kaposi's varicelliform eruption in a 38-year-old woman with
      rosacea. To our knowledge, this is the first case of Kaposi's varicelliform
      eruption associated with rosacea to be reported.

PMID- 15577763
TI  - Deep dermatophytosis caused by Trichophyton rubrum with concomitant disseminated
      nocardiosis in a renal transplant recipient.
AB  - Deep dermatophytosis and nocardiosis are uncommon infections. This article
      describes a patient who was immunosuppressed with deep dermatophytosis caused by
      Trichophyton rubrum and concurrent disseminated nocardiosis. The infections
      occurred 16 years after the patient underwent renal transplantation, and may have
      been related to tacrolimus therapy.

PMID- 15577764
TI  - Intralesional interferon alfa-2b treatment of keratoacanthomas.
AB  - BACKGROUND: Complete excision is not always easy when a keratoacanthoma is large
      or located in certain anatomic areas. An effective nonsurgical treatment would be
      desirable in such cases. OBJECTIVE: This was a pilot study of the effects of
      intralesional interferon alfa-2b in the treatment of rapidly growing
      keratoacanthomas. METHODS: A total of 4 large, rapidly growing keratoacanthomas,
      which were located on the lower lip, neck, and cheeks of the 4 different
      patients, were treated with intralesional interferon alfa-2b injection weekly.
      Serial photographs were taken to observe the course of responses. RESULTS: All
      lesions resolved completely in 5 to 7 weeks with acceptable cosmetic results.
      CONCLUSION: Intralesional interferon alfa-2b can be a treatment modality of these
      difficult lesions.

PMID- 15577765
TI  - Pelodera strongyloides infestation presenting as pruritic dermatitis.
AB  - Pelodera strongyloides is a free-living soil nematode of the order Rhabditida. We
      report an 18-year-old man with P strongyloides skin infestation. In this case,
      pruritic follicular papulopustules developed on the buttocks, then the right
      flank. Skin scrapings revealed many live rhabditiform larvae that were cultured
      adult worms and hatched ova, identified as P strongyloides . The eruption was
      treated effectively with topical 1% gamma-hexachlorocyclohexane ointment.

PMID- 15577766
TI  - Cutaneous adiaspiromycosis: a distinct dermatologic entity associated with
      Chrysosporium species.
AB  - Primary cutaneous infection with Chrysosporium, a saprophytic fungus commonly
      found in soil, is believed to be very rare, with only two previously reported
      cases. We present a case of localized cutaneous Chrysosporium in an
      immunocompromised heart transplant patient. Considering that the histology of the
      skin in this case is superimposable on that seen in pulmonary Chrysosporium known
      as adiaspiromycosis, we regard the cutaneous variant in the absence of pulmonary
      disease as a distinct dermatologic entity. The low frequency of reports of
      primary cutaneous Chrysosporium infection suggests either underreporting of this
      diagnosis in the literature, or misidentification of this fungus as another more
      common mycotic species sharing morphologic similarities. By amplifying our
      understanding of Chrysosporium infection in the skin, this disorder will be
      easier to identify and treat.

PMID- 15577767
TI  - Disseminated human papillomavirus type 11 infection in a patient with pemphigus
      vulgaris: confirmed by DNA analysis.
AB  - Depending on the type of epithelium infected, human papillomaviruses (HPVs) are
      often subclassified as "cutaneous" or "mucosal" types of HPV. HPV type 11 is a
      mucosal type of virus and infects the genital tract or larynx. Disseminated HPV
      11 infection involving multiple body sites in cases of pemphigus vulgaris (PV)
      has not been reported. We report here an unusual case of severe pemphigus
      vulgaris associated with disseminated HPV-11 infection on the arms, hands,
      axillae, chest, abdomen, and both thighs from the genital area, confirmed by the
      same DNA sequence.

PMID- 15577768
TI  - Nonhealing ulcer secondary to factor V Leiden mutation and cryofibrinogenemia.
AB  - Factor V Leiden is the most common genetic thrombophilia in people of European
      descent, and is important to recognize as it can have significant implications in
      dermatology. We report a case of a 30-year-old man who presented for evaluation
      and treatment of a chronic ulceration on the site of his stump following a below
      the knee amputation which had been performed for non-healing ulcerations. Despite
      a variety of treatments, his ulcer persisted. He was referred to a dermatologist
      who performed a biopsy that was interpreted ass non-specific, and treatment was
      started for pyoderma gangrenosum. Further investigation revealed a homozygous
      factor V Leiden mutation and cryofibrinogenemia. He was tapered off of the
      methylprednisolone and was improving on stanozolol. He healed well after surgery
      and no new ulcerations have developed. This case highlights the importance of
      considering this mutation in a non-healing leg ulcer.

PMID- 15577769
TI  - Cutaneous leishmaniasis in soldiers returning from deployment to Iraq.
AB  - Cutaneous leishmaniasis is becoming a frequently encountered problem in soldiers
      returning from deployments to areas in Southwest Asia. Two cases of cutaneous
      leishmaniasis diagnosed at a military treatment facility in soldiers returning
      from Iraq are presented. Diagnostic considerations and procedures are reviewed as
      are the histopathologic findings and treatment options.

PMID- 15577771
TI  - The role of oxidants and antioxidants in otitis media with effusion in children.
AB  - OBJECTIVE: Determine the possible role of oxidants and antioxidants in the
      pathogenesis of otitis media with effusion in children. STUDY DESIGN AND SETTING:
      Randomized controlled trial, tertiary referral center. The study group was made
      up of children with otitis media with effusion who were to undergo bilateral
      ventilation tube insertion and adenoidectomy. The control group was comprised of
      otherwise healthy children. The blood levels of antioxidants (retinol, beta
      carotene, alpha-tocopherol, laycopene, ascorbic acid, superoxide dismutase,
      glutathione peroxidase, GSH) and oxidation products (malondialdehyde) were
      determined before and 1 month after the operation in the study group and once
      only in the control group. These substances were also measured in the adenoid
      tissue and middle ear fluids. RESULTS: In the study group, the blood levels of
      antioxidants and oxidants before and after the operation were significantly
      different when compared with the control group (P < 0.05). In the study group,
      the blood antioxidant levels increased and oxidant levels decreased significantly
      after the operation (P < 0.05). The levels after the operation never reached
      those of the control group. CONCLUSIONS AND SIGNIFICANCE: Oxidants and
      antioxidants played a significant role in the pathogenesis of otitis media with
      effusion in children. These children are under significant oxidative stress.
      Insertion of a ventilation tube and adenoidectomy significantly decreased the
      oxidative stress in these patients, but could not normalize it completely.
      Additional studies are necessary in the clinical use of antioxidants in otitis
      media with effusion.

PMID- 15577772
TI  - A diagnostic paradigm for childhood idiopathic sensorineural hearing loss.
AB  - OBJECTIVE: Our objective was to determine the diagnostic yield of laboratory
      testing, radiological imaging, and GJB2 mutation screening in a large cohort of
      patients with differing severities of idiopathic sensorineural hearing loss
      (SNHL). DESIGN AND SETTING: We undertook a retrospective study of patients
      presenting with SNHL at our institution from 1993 to 2002. RESULTS: Laboratory
      testing had an extremely low yield. Patients with unilateral SNHL had a
      significantly higher imaging yield than those with bilateral. The diagnostic
      yield of GJB2 screening was significantly higher in patients with severe to
      profound SNHL than in those with less severe SNHL. However, a relatively large
      number of patients with mild to moderate SNHL had positive GJB2 screens.
      CONCLUSIONS: Based on diagnostic yields, we propose a cost-effective stepwise
      diagnostic paradigm to replace the more commonly used and costly simultaneous
      testing approach. EBM RATING: C.

PMID- 15577773
TI  - Complications of neonatal tracheostomy: a 5-year review.
AB  - OBJECTIVE: Study the complication rate of tracheostomy in premature infants and
      identify contributing factors. Setting Two university-based tertiary care
      children's hospitals. METHODS: The charts of 55 neonates who underwent
      tracheostomy between January 1997 and December 2002 were reviewed. Group 1
      included 32 infants born weighing < 1000 grams. Group 2 included 23 infants born
      weighing > or = 1000 grams. RESULTS: Group 1 infants had a higher incidence of
      comorbidities related to prematurity. Thirty-eight infants underwent tracheostomy
      due to ventilatory dependence, 13 for airway obstruction, and 4 for neurologic
      debilitation. Sixteen infants (29%) had a complication related to tracheostomy.
      There was no tracheostomy-related mortality. CONCLUSIONS: Tracheostomy in the
      preterm infant has the potential for significant morbidity. Meticulous technique,
      surgeon experience and specialized care may play a role in reducing the
      complication rate. Complications are usually minor and do not require additional
      surgical intervention. EBM RATING: C.

PMID- 15577774
TI  - The impact of sleep-disordered breathing on cognition and behavior in children: a
      review and meta-synthesis of the literature.
AB  - OBJECTIVES: The goal of this review is to provide a synthesis of the current
      literature addressing the effects of sleep-disordered breathing on cognition and
      behavior in children aged 2-18. STUDY DESIGN AND SETTING: A computerized search
      was performed to include studies between 1966 and 2001. Studies were assessed
      based on research question, sampling, intervention, outcomes, confounding, and
      statistical methods. Sensitivity analyses were performed for quantitative
      assessments of selection bias, misclassification, and confounding. RESULTS:
      Seventeen reports with 5312 patients were reviewed. The majority of these studies
      demonstrated poor sampling, insufficient consideration of confounders, and
      imprecise use of statistical tools. However, there was little evidence of bias in
      two studies when scrutinized using a sensitivity analysis. CONCLUSIONS: Despite
      suggested links between daytime behavior problems and neurocognitive deficits,
      there is little certainty for causality based on the quality of the evidence.
      SIGNIFICANCE: By discussing the quality of the current evidence, we hope to
      improve study design and contribute to the development of an understanding of
      this complex topic.

PMID- 15577775
TI  - Can history and physical examination reliably diagnose pediatric obstructive
      sleep apnea/hypopnea syndrome? A systematic review of the literature.
AB  - OBJECTIVE: Using an evidence-based technique, systematically review the
      literature to evaluate the accuracy of routine clinical history and physical
      examination in the diagnosis of obstructive sleep apnea/hypopnea syndrome (OSAHS)
      in the pediatric patient. STUDY DESIGN AND SETTING: The biomedical literature was
      systematically reviewed. Articles comparing the results of clinical evaluation to
      polysomnography (PSG) were selected. The level of evidence was assessed using
      established evidence-based medicine (EBM) guidelines. RESULTS: Twelve articles
      were identified using the search criteria. Eleven of 12 articles concluded that
      clinical evaluation is inaccurate in the diagnosis of OSAHS. The level of
      evidence was good to very good (Grade B/B+). CONCLUSION/SIGNIFICANCE: Clinical
      history and physical examination are not reliable for diagnosing OSAHS compared
      with overnight PSG. Complicating the interpretation of this work is the lack of a
      validated PSG threshold of clinically significant disease. There is an urgent
      need for the development of adequate screening tests with validated clinical
      outcomes. EBM RATING: B-3.

PMID- 15577776
TI  - Post-tonsillectomy hemorrhage: cold versus hot dissection.
AB  - OBJECTIVE: The aim of our study was to assess the rate of reactionary and
      secondary posttonsillectomy hemorrhage using "cold" dissection and bipolar
      diathermy and to determine whether there was any difference in the postoperative
      hemorrhage rate between the 2 methods. METHODS: This was a prospective study of
      all patients undergoing tonsillectomy between November 8, 1999 and November 7,
      2000 in a tertiary medical centre. The data collected included patient identity,
      age, gender, date of surgery, method of operation, and complications (if any).
      The timing of reactionary or secondary posttonsillectomy hemorrhage and the
      treatment were recorded. We hypothesized no difference in posttonsillectomy
      hemorrhage rates using the 2 methods. Chi2 test was used for statistical
      analysis. RESULTS: A total of 349 patients underwent tonsillectomy in the period
      (134 males, 215 females, mean age was 16.7 years). Of these, 337 were bilateral
      procedures, 145 patients had tonsillectomy using cold dissection, and 192
      patients had bipolar diathermy. Reactionary hemorrhage occurred in 1 patient
      (0.3%) and 31 patients (9.2%) developed secondary hemorrhage. The hemorrhage
      rates using cold dissection (n = 8) and bipolar diathermy (n = 24) were 5.5% and
      12.5%, respectively ( P < 0.05). CONCLUSIONS: The primary and secondary
      posttonsillectomy hemorrhage rates were 0.3 and 9.2%, respectively. Tonsillectomy
      using bipolar diathermy has a statistically significant higher secondary
      hemorrhage rate than using cold dissection (12.5% vs. 5.5%, P < 0.05).

PMID- 15577777
TI  - Nightly variability of sleep-disordered breathing measured over 3 nights.
AB  - OBJECTIVE: To examine the nightly variability of sleep-disordered breathing (SDB)
      as measured by the apnea-hypopnea index (AHI). STUDY DESIGN AND SETTING:
      Retrospective comparison of 3 sequential nights of testing performed in the home
      in 1091 patients who were referred for diagnostic testing of SDB. RESULTS: The
      Pearson and Intraclass correlation coefficients ranged between 0.88 and 0.90 for
      each pair of nights. Based on night 1, approximately 90% of patients were
      classified consistently with "AHI-high" (the highest AHI measured across the 3
      nights) using an AHI threshold of 5. However, 10% were misclassified on night 1
      relative to the highest AHI level. CONCLUSION AND SIGNIFICANCE: These findings
      suggest that (1) 1 night of diagnostic testing for SDB is not sufficient to
      diagnosis SDB in approximately 1 of every 10 cases, and (2) there is little, if
      any, significant nightly change in SDB in the home environment. EBM RATING: D.

PMID- 15577778
TI  - A comparison of polysomnography and a portable home sleep study in the diagnosis
      of obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To validate the role of a portable sleep monitor device (SNAP) in the
      diagnosis of obstructive sleep apnea syndrome (OSAS). Inter-reader variability
      was also assessed for both PSG and SNAP. STUDY DESIGN AND SETTING: Sixty
      consecutive adults referred for PSG at The University of Chicago Sleep Disorder
      Clinic were prospectively enrolled. RESULTS: There was no significant difference
      between total number of apnea and hypopnea, respiratory disturbance index (RDI),
      and minimum oxygen obtained by PSG and SNAP, but there was a significant
      difference between sleep time and mean oxygen. Pearson's correlation coefficient
      for RDI > or = 15 was 0.92. CONCLUSION: There was a significant correlation of
      RDIs between SNAP and PSG. SNAP has good sensitivity, specificity, positive and
      negative predictive values. Differences between SNAP and PSG could be attributed
      to inter-reader variability and not necessarily due to technical limitations of
      SNAP. SNAP is an excellent tool for the diagnosis of OSAS in the laboratory
      setting. Future studies should be performed to evaluate SNAP's accuracy in the
      home setting in the diagnosis of OSAS. EBM RATING: B-2.

PMID- 15577779
TI  - High-frequency ultrasound in the measurement of pediatric craniofacial integrity.
AB  - OBJECTIVE: This study evaluates the use of high-frequency ultrasound in the
      measurement of the material nature of the pediatric craniofacial skeleton. STUDY
      DESIGN AND SETTING: Three desiccated human skulls, aged 1 year, 5 years, and
      adult, underwent ultrasonic evaluation at 6 sites on each hemicranium. RESULTS:
      The overall mean signal reflection coefficients for the infant, child, and adult
      skulls are 98.8 mV (13.75 mV SD), 172 mV (24.5 mV SD), and 230 mV (23.5 mV SD),
      respectively. The mean signal reflection coefficient is positively correlated
      with increasing chronological age. Comparison of intrasubject signal patterns
      suggests bone density fields, which vary as a function of growth. CONCLUSION:
      High-frequency ultrasound provides accurate measurements of the osseous impedance
      of the craniofacial skeleton. Pattern analysis suggests increases in skull
      density with greater growth and age. SIGNIFICANCE: Although further testing must
      be performed in vivo, high-frequency ultrasound may accurately measure the
      osseous impedance of the pediatric craniofacial skeleton. EBM RATING: C.

PMID- 15577780
TI  - Esophageal incisions repair by CO2 laser soldering.
AB  - PURPOSE: This study evaluated the feasibility of fiberoptic CO2 laser soldering
      for the repair of esophageal injuries under tight temperature feedback control in
      an animal model. Healing was compared to conventional suture closure. MATERIALS
      AND METHODS: A CO2 soldering system equipped with infrared transmitting silver
      halide fibers was used. The soldered tissue temperature was monitored
      continuously, and laser power was adjusted to provide constant temperature. The
      procedure was done with 50% bovine serum albumin solder. Longitudinal incisions
      measuring 8 to 10 mm were made under general anesthesia in the cervical esophagus
      of 25 rats. Twenty rats (group I) underwent laser tissue bonding; 8 of which were
      tested in a preliminary study to determine optimal laser parameters. In the
      remaining 5 rats (group II, controls), closure was performed with 1 layer of 6/0
      Vicryl sutures. The rats were sacrificed 2, 3, 4, and 6 weeks postoperatively,
      and the esophagus was examined histologically. RESULTS: Optimal temperature was
      found to be 65 to 70 degrees C and optimal exposure time, 150 to 200 seconds.
      Laser soldering was successful in 9 of the 12 rats (75%) treated under optimal
      settings; suturing was successful in 4 of the 5 control rats (80%). There were no
      significant differences between the groups in healing or complication rates.
      CONCLUSIONS: These results indicate that the CO2 laser soldering technique is a
      valid option for the correction of esophageal tears or incisions in rats. The
      confirmation and extension of these findings in further studies with larger
      animals may ultimately lead to the routine in vivo use of temperature-controlled
      laser repair for the esophagus and other organs. This method lends itself to
      endoscopic bonding of tissues.

PMID- 15577781
TI  - Effects of viscosity, taste, and bolus volume on swallowing apnea duration of
      normal adults.
AB  - OBJECTIVE: The effects of viscosity, taste, and nectar-thick liquid bolus volume
      on swallowing apnea duration (SAD) were examined. STUDY DESIGN AND SETTING:
      Twenty-two adults, comprised of 10 males and 12 females, participated. SAD was
      assessed via nasal airflow during swallow conditions of viscosity (thin liquid,
      thick liquid, and puree), taste (water, apple juice, lemon concentrate), and
      nectar-thick liquid bolus volumes (5, 10, 15, and 20 mL) across three trials.
      RESULTS: A significant main effect of nectar-thick liquid bolus volume was found
      (P < 0.05). Viscosity and taste were not significant. CONCLUSIONS: SAD increased
      with increases in bolus volume; however, neither changes in bolus viscosity nor
      changes in taste affected SAD. SIGNIFICANCE: These findings indicate that since
      viscosity was not significant, the normative data previously published (by this
      PI) with 60 healthy adults stratified by age and gender can be utilized for
      comparison to disordered swallowing without regard to the bolus viscosity being
      used. EBM RATING: D.

PMID- 15577782
TI  - Lamina propria replacement therapy with cultured autologous fibroblasts for vocal
      fold scars.
AB  - OBJECTIVES: To develop a canine model of vocal fold scar and to evaluate its
      treatment with lamina propria replacement therapy using autologous cultured
      fibroblasts. MATERIALS AND METHODS: Full thickness of the lamina propria layer in
      canine vocal folds was injured with a laser. Fibroblasts were cultured and
      expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds
      were treated with 3 weekly injections of fourth, fifth, and sixth passage
      autologous fibroblasts. Mucosal waves and acoustic parameters were measured at
      baseline, after scarification, and several months after injection therapy.
      Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin,
      reticulin, and hyaluronic acid was performed. RESULTS: Nine beagle dogs were
      used, and 1 animal served as control. Vocal fold scarring resulted in absent or
      severely limited mucosal waves and significantly worse acoustic parameters.
      Significant improvements in mucosal waves and acoustic parameters were obtained
      after lamina propria replacement therapy. After therapy, mucosal waves became
      normal in 4 animals and near normal in the other 4. No statistical difference was
      found in mucosal waves between baseline and post-therapy. All animals tolerated
      therapy without complications. The treated vocal folds demonstrated an increased
      density of fibroblasts, collagen, and reticulin, a decreased density of elastin,
      and no change in hyaluronic acid. CONCLUSIONS AND SIGNIFICANCE: Therapeutic
      options for vocal fold scars are limited. Lamina propria replacement therapy in
      the form of autologous cultured fibroblasts improves mucosal pliability and
      returns normal or near normal mucosal waves in experimentally scarred vocal
      folds. This novel therapeutic modality may hold new promise for treating vocal
      fold scars.

PMID- 15577783
TI  - Bacterial tracheitis reexamined: is there a less severe manifestation?
AB  - OBJECTIVE: Bacterial tracheitis (BT) is a condition that can cause fatal airway
      obstruction. We evaluated our experience with BT over a 10-year period. STUDY
      DESIGN: Retrospective review of patients treated for BT between 1991 and 2001.
      RESULTS: Ninety-four cases were evaluated. The mean patient age was 7.9 years. At
      presentation, 60% were afebrile, and the mean WBC count was 10.8 x 10(3)/mm3 .
      Only 53% of patients required intubation. Younger children were more likely to
      require this intervention. S. aureus was the most commonly cultured bacteria,
      while isolation of M. catarrhalis was associated with a higher intubation rate. A
      pathologic virus was isolated in 64% of the 34 cultures performed. Only 9
      patients were described as "toxic," and 6 presented in respiratory extremis.
      There were no deaths. CONCLUSION AND SIGNIFICANCE: A subset of patients with
      tracheal membranes has a less severe clinical appearance. Nonetheless, these
      patients require debridement and aggressive medical treatment. We propose that
      the term "exudative tracheitis" (ET) better describes this entity. Older patients
      who are less systemically ill and rapidly respond to local and systemic therapy
      are characteristic of ET. EBM RATING: C.

PMID- 15577784
TI  - Randomized double-blinded, placebo-controlled clinical trial of famciclovir for
      reduction of Meniere's disease symptoms.
AB  - OBJECTIVE: To conduct a clinical trial of famciclovir for symptom control in
      Meniere's disease. STUDY DESIGN AND SETTING: Randomized, double-blinded placebo
      controlled clinical trial in a tertiary referral center, with 12 subjects in the
      active treatment arm and 11 subjects in the placebo arm. RESULTS: There were no
      serious adverse events. Twenty-five percent of the famciclovir group and 18% of
      the placebo group showed a reduction in number of vertigo spells, the primary
      efficacy endpoint. This difference was not statistically significant. All
      subjects improved in dizziness and health-related quality of life. There was a
      trend for the famciclovir arm to have less fluctuation in hearing relative to the
      placebo arm. CONCLUSION: No dramatic effects of famciclovir were found on vertigo
      or dizziness. Some promising effects on reduction of the fluctuation in hearing
      were observed. SIGNIFICANCE: Famciclovir may suppress the fluctuation of hearing
      in Meniere's disease, but had a minimal effect on vertigo or dizziness symptoms
      in this study. The probable multifactorial etiology in Meniere's disease requires
      that further studies be conducted to determine the effects of antiviral
      medications. EBM RATING: A.

PMID- 15577785
TI  - Changes in programming over time in postmeningitis cochlear implant users.
AB  - OBJECTIVE: Although successful cochlear implantation of patients with deafness
      following meningitis is expected, long-term stability of electrical current
      requirements has not been systematically evaluated. This study evaluated changes
      in programming for patients deafened by bacterial meningitis and stability of
      auditory performance over time. STUDY DESIGN AND SETTING: In this retrospective
      descriptive study, cochlear implant (CI) stimulation mode and performance of 14
      patients deafened by meningitis were compared with those of an age-matched
      control group of patients deafened by other causes. RESULTS: There were no
      significant differences in mean performance between the meningitis group and
      control group (P > 0.05). However, the postmeningitis group required
      progressively higher stimulation levels and higher programming modes over time as
      compared to the control group. CONCLUSIONS: Even with deafness accompanied by
      labyrinthine ossification attributed to meningitis, neural elements were present
      and could be stimulated. Because increasing levels of stimulation were required
      over time, postmeningitic children with CIs, and those with cochlear ossification
      in particular, may need frequent programming adjustments to maintain performance.
      SIGNIFICANCE: These patients need close follow-up of stimulation levels and
      programming modes postoperatively in order to perform optimally with CIs. EBM
      RATING: B-3.

PMID- 15577786
TI  - Direct round window application of gentamicin with varying delivery vehicles: a
      comparison of ototoxicity.
AB  - OBJECTIVE: To evaluate patterns of ototoxic damage sustained from gentamicin
      applied directly to the round window in varying delivery vehicles. SETTING: The
      search for a reliable method of drug delivery to the inner ear continues.
      Vehicles such as Gelfoam, hyaluronic acid, and fibrin may allow for a more
      reproducible pattern of ototoxic damage. STUDY DESIGN: Histological evaluation of
      vestibular and cochlear damage was performed on Mongolian gerbils after a known
      dosage of gentamicin in different delivery vehicles. RESULTS: Variable ototoxic
      damage was caused by Gelfoam and fibrin-based vehicles. No ototoxic damage was
      found in the Healon vehicle. The vehicle of fibrin and Gelfoam combined resulted
      in severe damage. There was no evidence of selective cochlear or vestibular
      ototoxicity in any of the vehicles tested. CONCLUSIONS AND SIGNIFICANCE: The
      fibrin/Gelfoam vehicle was the only delivery system to produce reliable damage.
      Ototoxic damage depended on the vehicle. We found no evidence for selective
      vestibular ototoxicity with gentamicin.

PMID- 15577787
TI  - Age-related histopathologic changes in the human cochlea: a temporal bone study.
AB  - OBJECTIVES: Previous reports on aging of human cochlea included subjects with ear
      diseases or ototoxic drugs. We studied spiral ganglion cells, hair cells, and
      lateral wall of cochlea from subjects without ear disease or ototoxic drugs.
      STUDY DESIGN: This study included 39 temporal bones from 24 subjects aged 1 day
      to 86 years. We assessed standard cytocochleograms, mean loss of fibrocytes in
      spiral ligament, and areas of stria vascularis. RESULTS: Losses of outer hair
      cells and fibrocytes were significantly greater in children, adults, and the
      elderly compared with infants. Spiral ganglion cell loss was significantly
      greater in adults and elderly compared with infants and children. Areas of stria
      vascularis of infants were significantly larger than the elderly. CONCLUSIONS:
      Degenerative changes of outer hair cells occur in children but spiral ganglion
      cells remain the same until around 20 years. Degeneration of stria vascularis due
      to aging appears to be slower than spiral ligament. EBM RATING: C.

PMID- 15577788
TI  - Phase 1 clinical trial results of the Envoy System: a totally implantable middle
      ear device for sensorineural hearing loss.
AB  - OBJECTIVES: This report will present the results of the USA Phase 1 clinical
      trials for the Envoy System (St. Croix Medical): A totally implantable middle ear
      hearing system for sensorineural loss. STUDY DESIGN: A prospective, single
      subject, repeated-measures, multicenter study was performed to evaluate safety
      and functionality of the Envoy System. Data collected included Abbreviated
      Profile of Hearing Aid Benefit, bone conduction threshold, speech reception
      threshold, functional gain, word recognition, and adverse events. Testing was
      performed unaided, with the patient's best-fit hearing aid, and post device
      activation at 2 (trial endpoint) and 4 months. RESULTS: Five of 7 patients at the
      2-month postactivation period had working systems. All 5 patients perceived
      benefit increases with the Envoy System over their best-fit hearing aid,
      including communication in high background noise levels. Word recognition was
      improved over hearing aids. Functional gain and speech reception thresholds were
      similar for the Envoy device and hearing aids. CONCLUSIONS: The feasibility trial
      has shown the Envoy device, a totally implantable middle ear device, can safely
      sense and drive the ossicular chain. EBM RATING: B-2.

PMID- 15577789
TI  - Diagnosis of middle ear disease using tympanograms and digital imaging.
AB  - OBJECTIVE: The study investigates the ability of physicians with different levels
      of training to accurately identify middle ear (ME) pathology using tympanograms
      and tympanic membrane (TM) digital photographs. STUDY DESIGN AND SETTING: Groups
      of medical students, internal medicine residents, and attending and resident
      otolaryngologists were presented with a set of 50 matched tympanograms and
      photographs of TMs. The physicians were asked to differentiate between a normal
      and an abnormal-appearing TM. The sensitivity and specificity of diagnosis of ME
      pathology by physicians were compared with the gold standard, examining the ME
      cavity for pathology during myringotomy. RESULTS: The sensitivity did not vary
      among physicians with different levels of training; however, specificity improved
      with an increase in physician experience. CONCLUSIONS AND SIGNIFICANCE: This
      study establishes a baseline for accuracy of diagnosis of ME pathology using
      tympanograms and photographs of TMs as compared with binocular otomicroscopy and
      the gold standard, myringotomy. EBM RATING: B-2.

PMID- 15577790
TI  - Resorption rate and biocompatibility characteristics of two polyester ventilation
      tubes in a guinea pig model.
AB  - OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of
      2 polyester ventilation tubes, and to determine whether soap and water exposure
      accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D,
      L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed
      into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the
      tubes was determined by weekly otoscopic examination. Biocompatibility was
      assessed by comparing auditory brainstem response (ABR) thresholds and by
      examining tympanic membrane changes following tube resorption. Shah minigrommet
      ventilation tubes were used as controls. In the second portion of this study,
      implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and
      water (1:5) until complete resorption was observed. Biocompatibility was assessed
      by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes
      remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than
      the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube
      interface demonstrated equivalent findings for auditory thresholds and tissue
      histopathology at the implant site compared to nonresorbable controls. The
      resorption behavior was not altered by exposure to soap and water. Tympanic
      membranes of all animals following tube degradation and soap water exposure were
      intact with minimal scarring and no signs of persistent foreign body response.
      The histological analysis showed that implantation of resorbable tubes was not
      accompanied by secondary infection with otorrhea through the tube, did not result
      in a permanent perforation or dislocation of the tube into the middle ear cavity,
      and was not followed by excess tympanosclerosis or localized or diffuse membrane
      atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization
      tubes demonstrate predictable resorption behavior and similar biocompatibility
      characteristics when compared with nonresorbable Shah minigrommet ventilation
      tubes. Exposure to soap water does not accelerate polyester tube degradation nor
      change the host tissue response during the indwelling period or after complete
      resorption. The data suggests that resorbable ventilation tubes are substantially
      equivalent to other FDA-approved tympanostomy devices with regard to safety and
      biocompatibility in the guinea pig model examined and may provide improved
      clinical performance by combining this approach with sustained release
      technology. EBM RATING: B-2.

PMID- 15577791
TI  - Conventional behind-the-ear hearing aids after subtotal petrosectomy with blind
      sac closure.
AB  - OBJECTIVE: To overcome the limitations of monaural hearing resulting from a
      subtotal petrosectomy and blind sac closure by fitting of a behind-the-ear
      hearing aid. STUDY DESIGN: Three patients were fitted with aids. Patient
      satisfaction and the decision to buy the aids were recorded. RESULTS: Three
      patients reported good hearing result despite the absence of the middle ear
      structures. CONCLUSION: For patients troubled by the limitations imposed on
      hearing with a unilateral conductive loss following a subtotal petrosectomy and
      blind sac closure, a behind-the-ear aid is a simple and easy option to try, if
      the residual canal allows fitting of the aid.

PMID- 15577792
TI  - Impaired visual suppression of manually rotated vestibuloocular reflex indicates
      the need of further evaluation by MRI and MRA in patients with vertigo.
AB  - OBJECTIVE: MRI and MRA are accepted as valuable methods for diagnosing vertigo,
      although they are costly and time-consuming. Thus, some indicator of the
      necessity of a detailed evaluation by MRI and MRA is desirable. STUDY DESIGN AND
      SETTING: To assess the usefulness of an impairment of the visual suppression (VS)
      as an indicator, the relation between abnormal findings on MRI and/or MRA and
      impairment of the VS of manually rotated vestibuloocular reflex (VOR) was
      retrospectively examined in 40 consecutive patients suffering from vertigo.
      RESULTS: 12 of 23 patients with a low VS% were found to have a pathologic
      condition on MRI and/or MRA, however, no abnormality was found in any of the
      patients with a normal VS%. The rates of abnormality on MRI and/or MRA
      significantly differed between the 2 groups (chi2, P = 0.0004). CONCLUSION: The
      VS% is thought to be a good indicator of the need for further evaluation by MRI
      and MRA in vertiginous patients.

PMID- 15577793
TI  - Salvage of partial facial soft tissue avulsions with medicinal leeches.
AB  - BACKGROUND: Medicinal leeches have been demonstrated to be extremely useful and
      safe in the salvage of venous outflow compromised tissue, particularly in digit
      replants and various forms of flaps. OBJECTIVE: To demonstrate the utility of
      medicinal leeches in the salvage of venous outflow-compromised traumatic soft
      tissue avulsions in key facial structures. METHODS: A retrospective review of 4
      cases involving the external ear, nose, lip, and scalp in which apparent venous
      outflow compromise was present. Medicinal leeches were applied acutely in each of
      these 4 cases, salvaging each of the partially avulsed soft tissue segments.
      RESULTS: Complete or near complete salvage of each soft tissue segment after
      using medicinal leeches. CONCLUSIONS: Although it is unusual for a partial soft
      tissue avulsion of the face to require medicinal leech therapy, situations may
      occur in which there is adequate arterial inflow but inadequate venous outflow.
      In such cases, medicinal leeches may play a very important role in salvaging the
      soft tissue segment. This is particularly important in vital structures such as
      the ear, nose, lip, and eyelid in which acute or secondary reconstruction is
      complex. EBM RATING: C.

PMID- 15577794
TI  - Software-enabled CT analysis of optic nerve position and paranasal sinus
      pneumatization patterns.
AB  - OBJECTIVE: Delineate the relationships among the optic nerve (CN II), the
      sphenoid sinus, and the sphenoethmoid cell. STUDY DESIGN: High-resolution CT
      scans of 64 frozen human cadavers were obtained on a Siemens VolumeZoom CT
      scanner (Munich, Germany) and transferred to a CBYON Suite Doctor Station version
      2.6 (CBYON, Mountain View CA) for standardized review. RESULTS: Pneumatization
      around CN II was categorized into 5 types: no adjacent pneumatization (type 0),
      pneumatization adjacent to CN II (type 1), adjacent pneumatization with
      indentation (type 2), pneumatization of <50% CN II circumference (type 3), and
      pneumatization of >50% CN II circumference (type 4). The prevalence of types 0 to
      4 CN II position relative to the sphenoid sinus was 4.7%, 25.8%, 39.8%, 14.1%,
      and 15.6%, respectively. The prevalence of sphenoethmoid cells was 28.1%. The
      prevalences of types 0, 1, 2, 3, and 4 CN II positions relative to the
      sphenoethmoid cell was 5.6%, 58.3%, 25%, 2.8%, and 8.3% respectively.
      CONCLUSIONS: Software-enabled CT review facilitated precise study of the anatomic
      relationships of CN II. Caution must be exercised during sinonasal surgery to
      minimize the risk of inadvertent CN II injury. EBM RATING: D.

PMID- 15577795
TI  - Endoscopic sinus surgery in patients older than sixty.
AB  - OBJECTIVE: Rhinosinusitis is the sixth most common chronic condition of the
      elderly. Functional endoscopic sinus surgery (FESS) has developed over the last
      20 to 30 years into a widely accepted treatment modality for chronic
      rhinosinusitis in adults who have failed maximal medical management. The aim of
      this study was investigate the safety and efficacy of FESS in the geriatric
      population as compared to that of the adult population. METHODS: Retrospective
      review of prospective measurement of outcomes in consecutive patients over 60
      years of age who underwent FESS. Fifty-six patients over 60 years of age
      underwent FESS and were evaluated preoperatively and postoperatively at 3, 6, and
      12 months with the Sino-Nasal Outcome Test-20 (SNOT-20) questionnaire, and a
      rigid nasal endoscopy scoring system. Data analysis was performed using the
      Student's t test to compare mean scores. Any complications were noted. RESULTS:
      Patients evaluated by the SNOT-20 scoring system experienced 64% improvement of
      symptom scores at 3 months, 73% improvement at 6 months, and 75% improvement at
      12 months. Rigid nasal endoscopy scores improved by 76% at 3 months, 65% at 6
      months, and 76% at 12 months. There were very few minor complications and no
      major complications of the surgery. These results are comparable to those of the
      literature that address outcomes in the adult population undergoing FESS.
      CONCLUSIONS: FESS in the geriatric population is a safe and effective treatment
      modality for rhinosinusitis that is refractory to medical therapy. EBM RATING: C.

PMID- 15577796
TI  - Functional outcomes following chemoradiotherapy for head and neck cancer.
AB  - OBJECTIVE: To study functional outcomes following concurrent chemoradiotherapy of
      head and neck cancer. METHODS: A retrospective chart review assessed diet,
      feeding tube use, and tracheotomy pretreatment and 3, 6, 12, and 24 months
      posttreatment. RESULTS: Of 196 patients who underwent chemoradiotherapy between
      1990 and 2002, 148 (76%) required feeding tubes immediately posttreatment; 150
      (77%) required nutritional support at 3 months. By 12 months, 92% were tube-free
      and 83% resumed near-normal diet. Of 17 patients (9%) with tracheotomy
      posttreatment, 71% were decannulated by 6 months. Stage IV disease strongly
      predicted prolonged feeding tube use and slow recovery of diet; age > or =60 also
      predicted slow recovery. Primary site, gender, and radiotherapy schedule did not
      predict functional recovery after adjusting for stage and age. CONCLUSION: Few
      patients required tracheotomy before or during chemoradiotherapy. Many patients
      required feeding tubes and nutritional support for several months following
      therapy, but most were tube-free and eating near-normal diets within 1 year. EBM
      RATING: C.

PMID- 15577797
TI  - Radial forearm free tissue transfer reduces complications in salvage skull base
      surgery.
AB  - OBJECTIVE: Patients who undergo skull base resection after prior surgery or
      radiation may be at high risk for complications when local flaps alone are used
      for reconstruction. To determine whether the complication rate could be reduced,
      fasciocutaneous free tissue transfer was used to reinforce the dural closure in
      patients who had prior skull base surgery or radiation. METHODS: This study is a
      case series of 20 patients (14 males, 6 females, aged 8-79 years of age with a
      mean of 47.7 years) from 1997 to 2001 who had prior skull base surgery or
      radiation, and underwent salvage skull base resection without large volume
      defects. All patients had a radial forearm free tissue transfer to reinforce the
      dural closure. Six patients had an osseous component to the forearm flap to
      provide vascularized bone to the orbital rim. RESULTS: The overall local
      complication rate was 35%. Three patients (15%) had major complications including
      1 case of meningitis, 1 case of cerebrospinal fluid leak, and 1 case of a flap
      requiring venous salvage. There were no flap failures, 1 idiopathic median nerve
      palsy, and no pathologic radius bone fractures. CONCLUSION: Reconstruction with
      fasciocutaneous free tissue transfer for high-risk patients with low-volume dural
      defects following skull base resection can minimize the risk of major
      postoperative complications. EBM RATING: C.

PMID- 15577798
TI  - A comparison of the results of monolayer versus smear cytopreparatory techniques
      for fine-needle aspiration in 100 consecutive patients undergoing thyroidectomy:
      a surgeon's perspective.
AB  - OBJECTIVE: To compare thyroid fine-needle aspiration (FNA) using monolayer (MT)
      versus conventional smear (CS) cytopreparatory techniques with final histology.
      STUDY DESIGN: Retrospective review of 100 consecutive thyroidectomies. Setting
      Tertiary care university affiliated medical center. RESULTS: 26% of MT aspirates
      were inadequate compared with 3% of CS aspirates (P < 0.05). The negative
      predictive values for MT and CS were 86% and 100%, respectively. The positive
      predictive values for MT and CS were 69% and 90%, respectively. CONCLUSIONS:
      Fewer inadequate specimens will be obtained with CS than with MT. A clinician
      performing FNA can obtain adequate specimens at a rate comparable to that of a
      hospital-based cytopathologist. SIGNIFICANCE: CS provides greater assurance to
      the patient and the surgeon that a thyroid nodule with a FNA interpreted as
      benign can be observed. A higher percentage of patients with malignant tumor will
      receive thyroidectomy with the use of CS technique for FNA. EBM RATING: B-3.

PMID- 15577799
TI  - Neck mass due to thrombosis of the jugular vein in patients with cancer.
AB  - The hypothesis that jugular thrombosis (JT) may cause a mass in the cervical
      region is usually overlooked. The objective of the present study was to identify
      the characteristics of neck masses resulting from JT in cancer patients and to
      analyze the possible reasons for their formation. A retrospective study was
      conducted on 8 patients with JT affected by 3 types of neoplasia, ie, carcinomas
      (3 cases), adenocarcinomas (3 cases), and lymphomas (2 cases) located in the
      breast, digestive apparatus, lymphatic system (2 cases each), lung and an
      undetermined site (1 case each), diagnosed over the last 12 years. The most
      frequent symptom of JT was the presence of a mass in the supraclavicular space
      (62.5% of cases) deeply located on the anterior margin of the sternocleidomastoid
      muscle and diagnosed by computed tomography and ultrasound. The masses were
      slightly hardened, with a clearly defined upper limit and an imprecise lower
      limit and with an irregular surface. The patients also presented with cough,
      hoarseness, pain during movements, facial edema, and collateral circulation. In
      one of the patients with a lung cancer, JT symptoms preceded the symptoms of
      cancer by 2 months. Hypercoagulation, compression, and invasion of a vessel
      possibly explain the occurrence of JT in these patients.

PMID- 15577800
TI  - Treatment of 125 sinonasal tumors: prognostic factors, outcome, and follow-up.
AB  - We reviewed our experience with sinonasal cancer patients to assess the
      prognostic factors. Between 1974 and 1995, we enrolled 125 patients (58 + 16
      years [mean age + SD]; 94 males and 31 females). Tumor stage distribution was:
      T1, 64 patients; T2, 36 patients; and T3, 25 patients. Surgery as a primary
      treatment was selected for 106 patients (55 cases of surgery alone, 40 cases of
      surgery plus radiotherapy, and 11 cases of surgery plus chemotherapy with/without
      radiotherapy). The 1-, 5-, and 10-year overall survival was 75.0%, 37.2%, and
      24.7%, respectively. The parameters with statistical prognostic significance were
      nodal stage, locoregional failure, and tumor stage. Histological type and primary
      site had no prognostic value. There were no significant survival differences
      between surgery alone and surgery plus radiotherapy. Sinonasal tumors have a poor
      survival, despite early diagnosis, radical surgical resection, and strict follow
      up. Radiotherapy seems not to be clearly necessary in stage T1.

PMID- 15577801
TI  - Surface electromyographic studies of swallowing in normal subjects: a review of
      440 adults. Report 3. Qualitative data.
AB  - OBJECTIVE: Surface electromyographic studies were performed on 440 normal adults
      to describe and evaluate different types of normal swallows clinically useful for
      ENT department. Study design Prospective observational study of healthy
      volunteers. METHODS: EMG recordings were made using stick-on surface electrodes.
      Rectified and filtered EMG signals were evaluated. Parameters evaluated include
      the graphic configuration of activity of the orbicularis oris, masseter,
      submental group, and infrahyoid muscles, the last 2 covered by platysma, during
      single swallowing and continuous drinking. Four tests were examined: voluntary
      saliva swallows, voluntary separate swallows as normal, voluntary separate
      swallows of excessive amount of water (20 mL), drinking of 100 mL of water.
      Graphic recording of activity of the above-mentioned muscles during swallowing
      and drinking were evaluated for groups of adults of different ages. RESULTS:
      There are several types of normal swallows as seen at the surface EMG records.
      There was no difference between EMG recordings of male and female swallows. Only
      group of elderly patients (age 70+) shows age-induced differences in recorded
      swallows. There are two main types of normal swallow: single-share and double
      share swallows. The oral phase of swallowing, being under conscious control, is
      very variable and should not be taken into consideration during evaluation of
      records. Final oral, pharyngeal, and initial esophageal stages of swallowing can
      be defined and evaluated at the rectified and filtered surface EMG record.
      CONCLUSION: The normal muscle activity during swallows and drinking has several
      graphic patterns which can be identified and described similar to EKG records
      when surface EMG is rectified and filtered. The method of EMG recording is quick
      and simple, and can be used for screening and evaluation purposes in outpatient
      and inpatient ENT departments. These parameters represent activities required for
      normal deglutition, and can be used to identify abnormalities in ENT patients,
      and provide a basis for comparison of swallowing performance both within and
      between patients. These normal data form a valuable basis for future comparison
      with patients in pre- and postoperative stages and in EMG monitoring during ENT
      treatment.

PMID- 15577802
TI  - Habitual risk factors for head and neck cancer.
AB  - Chronic tobacco smoking and alcohol consumption are well-established risk factors
      for the development of squamous cell carcinoma (SCC) of the head and neck. There
      are, however, a variety of other habitual and culturally based activities that
      are less commonly seen in the Western world and that are also risks factors for
      the development of this type of cancer. In this era of globalization, many of
      these habits have now crossed borders and appear in various areas throughout the
      world. This article reviews habitual and social risk factors for cancer of the
      head and neck, excluding smoking and alcohol consumption. These factors include
      chewing tobacco and snuff, areca nut in its various forms, Khat leaves, and the
      drinking of Mate. EBM RATING: D.

PMID- 15577803
TI  - Adenoid cystic carcinoma of the submandibular gland: a 35-year review.
AB  - OBJECTIVES: To evaluate the treatment results of adenoid cystic carcinoma (ACC)
      of the submandibular gland at a single institution during a 35-year period. STUDY
      DESIGN & SETTING: A retrospective review was performed by examining the records
      and reviewing the pathology of 22 patients with ACC of the submandibular gland
      treated at UCLA Medical Center from June 1963 to December 1997. RESULTS: Seven
      men and 15 women with an age range of 23 to 85 years (median, 48 years) were
      treated. Surgical intervention was performed in 21 patients. All patients with
      advanced tumor size, perineural invasion, microscopically positive surgical
      margins, or regional neck metastases received postoperative adjunctive therapy,
      primarily radiotherapy. Follow-up varied from 6 months to 181 months (median, 67
      months). Disease-free survival at 3, 5, and 10 years was 66%, 57%, and 41%
      respectively, whereas overall survival was 76%, 70%, and 37%, respectively (note:
      5- and 10-year survival rates are not statistically conclusive due to the small
      sample size). CONCLUSIONS: We report fairly high disease-free survival rates in
      this patient population and a number of prognostic trends are evident. Early
      diagnosis, wide surgical intervention, and postoperative radiation are associated
      with a favorable prognosis. Advanced tumor size, positive surgical margins,
      perineural invasion, and local recurrence of the tumor are associated with an
      unfavorable prognosis. EBM RATING: C.

PMID- 15577804
TI  - An overview of office-based ultrasonography: new versions of an old technology.

PMID- 15577805
TI  - Internal auditory canal decompression and cochlear implantation in Camurati
      Engelmann disease.

PMID- 15577806
TI  - Laryngectomy for fungal abscesses of the larynx.

PMID- 15577807
TI  - Recurrent and destructive nasal polyposis in 2 siblings: a possible case of
      Woakes' syndrome.

PMID- 15577808
TI  - Sinonasal hemangiopericytoma.

PMID- 15577809
TI  - Triple discrete fungus balls of the paranasal sinuses.
AB  - Paranasal sinus fungus balls occur usually in single sinus, most frequently the
      maxillary sinus. Multisinus localization was found only 6% in the largest review
      of this disease entity. Even multiple sinuses involved, these sinuses were mostly
      contiguous. Bilateral involvement was rare in the literature. Nevertheless, there
      has never been a report of three discrete sinus fungus balls in the same patient.
      This report represents the first case of the paranasal sinus fungus balls
      presenting in triple discrete sinuses at once.

PMID- 15577810
TI  - Laryngeal nerve function after total laryngeal transplantation.
AB  - The first successful composite human laryngeal transplantation was performed by a
      team led by the senior author on January 4, 1998. The recipient was a 40-year-old
      male who had sustained a crush injury to his larynx 20 years prior, rendering him
      aphonic. Multiple previous attempts for reconstruction at an outside hospital
      were unsuccessful. The donor was a 40-year-old male who had died from a ruptured
      cerebral aneurysm. The specifics of the procedure have been detailed elsewhere.
      Throughout the patient's postoperative course, serial fiberoptic evaluations and
      voice testing were performed to evaluate laryngeal reinnervation reflected in
      phonatory function. We herein report the results of these exams, as well as the
      results of electromyographic recordings of the laryngeal musculature 4 years
      posttransplantation.

PMID- 15577811
TI  - Ectopic thyroid tissue with follicular adenoma mimicking carotid body tumor.

PMID- 15577812
TI  - Postauricular epithelioid sarcoma.

PMID- 15577813
TI  - Acinic cell carcinoma of the tongue base.

PMID- 15577814
TI  - Primary lymph node malignant gastrinoma with metastasis to Virchow's node: a case
      report.

PMID- 15577815
TI  - Renal cell carcinoma metastatic to the larynx.

PMID- 15577816
TI  - Rhinosinusitis: Establishing definitions for clinical research and patient care.

PMID- 15577818
TI  - Statistical errors in immunologic research.
AB  - Medical research articles have always been subject to errors in reporting
      statistical results. Although most of these are minor, they raise questions about
      the integrity of medical research. Most of the errors come from a
      misunderstanding about the tools used in statistical analysis. This article
      discusses some of the most frequent errors and provides examples of how to deal
      with them correctly.

PMID- 15577820
TI  - IL-17 cytokine family.
AB  - A new family of cytokines, IL-17, has recently been defined that reveals a
      distinct ligand-receptor signaling system. Functional studies have provided
      evidence for its importance in the regulation of immune responses. Notably, 3
      members, IL-17A, IL-17E (IL-25), and IL-17F, have been best characterized both in
      vitro and in vivo , and have been shown to be proinflammatory in nature. This
      proinflammatory activity is exemplified by their involvement in pulmonary
      inflammatory responses, in which both IL-17A and IL-17F are involved in the
      recruitment of neutrophils, and IL-17E is able to induce T H 2 cytokine
      production and eosinophilia. Although the elucidation of a detailed mechanism of
      action continues to be an active area of research, the potent inflammatory
      activity and its association with various human disease states suggest this new
      cytokine family as an important contributor to the pathophysiology of human
      disease conditions, in particular the pulmonary diseases.

PMID- 15577822
TI  - Childhood infections, the developing immune system, and the origins of asthma.
AB  - Asthma is an immune-mediated inflammatory condition characterized by increased
      responsiveness to bronchoconstrictive stimuli. Viruses have been shown to play an
      important role in asthma, with viral infection being present during about 85% of
      exacerbations. However, the role they play in the onset of asthma is more
      controversial. Some respiratory viral infections might be protective, but there
      is a strong association between respiratory syncytial virus-induced bronchiolitis
      in infancy and recurrent wheeze up to 12 years of age. Both the respiratory tract
      and the immune system undergo rapid maturation during the first year of life, and
      it seems that postnatal development is affected by and affects responses to viral
      infections. Understanding postnatal developmental changes in the immune system
      might help to explain the origins and pathogenesis of asthma and thus the
      effectiveness or ineffectiveness of specific asthma therapies.

PMID- 15577823
TI  - Tacrolimus reduces urinary excretion of leukotriene E(4) and inhibits aspirin
      induced asthma to threshold dose of aspirin.
AB  - BACKGROUND: The exact mechanism of aspirin-induced asthma is not clear. It has
      been postulated that precipitation of asthma attacks by aspirin is linked to
      inhibition of COX activity and massive release of cysteinyl leukotriene into the
      airway. Tacrolimus, a macrolide-derived immunosuppressant, is used for
      immunosuppression in organ transplantation and also for allergic diseases such as
      atopic dermatitis. OBJECTIVE: We evaluated the effects of tacrolimus in aspirin
      induced asthma by using a double-blind, crossover study design. METHODS: Twelve
      patients with aspirin-induced asthma (male:female, 3:9; mean age +/- SD, 36.7 +/-
      7.2 years) received either tacrolimus (0.1 mg/kg) or placebo 2 hours before the
      threshold dose of oral aspirin. RESULTS: In the placebo arm, oral aspirin
      significantly decreased FEV 1 concomitant with significant increases in sputum
      eosinophilic cationic protein and urinary leukotriene E(4) levels. Tacrolimus
      significantly inhibited bronchoconstriction and abrogated aspirin-induced
      increase in both sputum eosinophilic cationic protein and urinary leukotriene
      E(4) levels. CONCLUSION: The current study suggested that tacrolimus inhibited
      bronchoconstriction to a threshold dose of aspirin by inhibition of cysteinyl
      leukotriene excretion.

PMID- 15577824
TI  - Atopic characteristics of children with recurrent wheezing at high risk for the
      development of childhood asthma.
AB  - BACKGROUND: Few studies have characterized the atopic profile of toddler-aged
      children with recurrent wheezing at high risk of the development of persistent
      asthma. Objective We sought to determine the atopic profile of toddler-aged
      children with frequent wheeze at high risk for the development of persistent
      asthma who either had a parental history of asthma, a personal history of atopic
      dermatitis, or both. METHODS: Participants enrolled in the Prevention of Early
      Asthma in Kids study (n = 285) on the basis of a modified Asthma Predictive Index
      were characterized on the basis of allergy and asthma questionnaire responses and
      allergy skin puncture test results. RESULTS: The majority of the children (60.7%,
      n = 148) were sensitized to either food or aeroallergens. Male children were
      significantly more likely to be sensitized to aeroallergens ( P = .03) and to
      have a blood eosinophil level of 4% or greater ( P = .03) and a total serum IgE
      level of greater than 100 IU/mL ( P = .0004). Additionally, eosinophilia and
      total serum IgE level had the strongest correlation with aeroallergen
      sensitization. CONCLUSION: The high prevalence of aeroallergen sensitization in
      this high-risk cohort suggests that aeroallergens might have an important role in
      the early development of asthma. As such, the Prevention of Early Asthma in Kids
      cohort appears to be an appropriate cohort in which to test whether early
      intervention with an inhaled corticosteroid can significantly attenuate, or
      perhaps even prevent, the allergic march from the initial stages of allergic
      sensitization to the subsequent development of asthma in toddlers with episodic
      wheezing.

PMID- 15577825
TI  - Relationship between adherence to inhaled corticosteroids and poor outcomes among
      adults with asthma.
AB  - BACKGROUND: Regular use of inhaled corticosteroids (ICSs) can improve asthma
      symptoms and prevent exacerbations. However, overall adherence is poor among
      patients with asthma. Objective To estimate the proportion of poor asthma-related
      outcomes attributable to ICS nonadherence. METHODS: We retrospectively identified
      405 adults age 18 to 50 years who had asthma and were members of a large health
      maintenance organization in southeast Michigan between January 1, 1999, and
      December 31, 2001. Adherence indices were calculated by using medical records and
      pharmacy claims. The main outcomes were the number of asthma-related outpatient
      visits, emergency department visits, and hospitalizations, as well as the
      frequency of oral steroid use. RESULTS: Overall adherence to ICS was
      approximately 50%. Adherence to ICS was significantly and negatively correlated
      with the number of emergency department visits (correlation coefficient [ R ] = 
      0.159), the number of fills of an oral steroid ( R = -0.179), and the total days'
      supply of oral steroid ( R = -0.154). After adjusting for potential confounders,
      including the prescribed amount of ICS, each 25% increase in the proportion of
      time without ICS medication resulted in a doubling of the rate of asthma-related
      hospitalization (relative rate, 2.01; 95% CI, 1.06-3.79). During the study
      period, there were 80 asthma-related hospitalizations; an estimated 32
      hospitalizations would have occurred were there no gaps in medication use (60%
      reduction). CONCLUSIONS: Adherence to ICS is poor among adult patients with
      asthma and is correlated with several poor asthma-related outcomes. Less than
      perfect adherence to ICS appears to account for the majority of asthma-related
      hospitalizations.

PMID- 15577826
TI  - Mapping of conformational IgE epitopes on Phl p 5a by using mimotopes from a
      phage display library.
AB  - BACKGROUND: Phl p 5 represents a major allergen of timothy grass pollen (Phleum
      pratense). Detailed knowledge about the structures responsible for IgE binding
      would allow the design of a novel generation of allergy vaccines. OBJECTIVE: We
      aimed to characterize the IgE epitopes of Phl p 5a using phage display combined
      with a molecular modeling approach. METHODS: Phl p 5a-specific IgE from sera of
      patients with grass pollen allergy was used for screening of a random peptide
      phage library displaying constrained decamers. RESULTS: Fifteen phage clones that
      shared sequence motifs and could be grouped into families were selected by using
      Phl p 5a-specific IgE. Peptide alignment with the solvent-accessible amino acids
      of Phl p 5a revealed 3 sequence sections with frequent hits of identical or
      similar amino acids. On the surface of Phl p 5a, these sections assembled in
      compact patches, most likely representing conformational IgE epitopes, whereas no
      matching clusters were found on the back sides of the 2 Phl p 5a halves. In
      surface plasmon resonance experiments, the high-affinity interaction between IgE
      and Phl p 5 could be competed by phage-displayed peptides up to 24%, indicating
      that they represent true epitope mimics (ie, mimotopes). Allergen-specific
      immunogenicity of the mimotopes was proved in Biozzi mice. CONCLUSION: The
      selected mimotopes facilitated the localization of conformational IgE epitopes of
      Phl p 5. We suggest them to be suitable candidates for the development of an
      epitope-specific immunotherapy.

PMID- 15577827
TI  - An antigen-independent but not antigen-specific T(H)1 response provides
      protection in the murine airway inflammation model.
AB  - BACKGROUND: Atopic disorders are associated with an imbalanced T(H) cell response
      biased toward a strong T(H)2 type, resulting in excessive production of IgE
      antibodies, eosinophil recruitment and activation, and mast cell degranulation.
      Restoring the T(H)1-T(H)2 balance by increasing the antigen-specific T(H)1
      response has been pursued for specific allergy immunotherapy. Synthetic
      oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG) are strong
      T(H)1 adjuvants and are being investigated for allergy immunotherapy. OBJECTIVE:
      This study was designed to investigate the protective role of antigen-specific
      T(H)1 responses induced by epidermal powder immunization with ovalbumin (OVA) and
      CpG in a murine airway inflammation model. METHODS: An allergy model was used in
      which BALB/c mice were sensitized and then challenged with OVA. Mice received
      prophylactic or therapeutic immunizations with OVA, CpG, or both. After
      challenge, pulmonary inflammation and cell infiltration were measured on the
      basis of BAL cell counts and lung histology. Immune response was determined by
      measuring the levels of lavage cytokines and serum antibodies. RESULTS:
      Coadministration of OVA and CpG by means of subcutaneous injection or epidermal
      powder immunization, although inducing a strong T(H)1 response, neither
      suppressed T(H)2 cytokines nor offered protection against pulmonary eosinophilia
      and histopathology in a mouse challenge model. However, when CpG was used as a
      stand-alone treatment of previously sensitized animals, protection against
      allergic airway inflammation was observed. After challenge with OVA, eosinophilia
      was suppressed in the lungs of the CpG-treated mice. CONCLUSION: This finding
      argues against the approach of boosting an allergen-dependent T(H)1 response and
      favors induction of an antigen-independent T(H)1 response for allergy
      immunotherapy.

PMID- 15577828
TI  - Expression of prostaglandin E(2) receptor subtypes on cells in sputum from
      patients with asthma and controls: effect of allergen inhalational challenge.
AB  - BACKGROUND: Prostaglandin (PG) E 2 binds to 4 G-protein-coupled receptors
      designated EP 1 through EP 4 . Although PGE 2 plays an immunomodulatory role in
      asthma, there is little information on the expression of PGE 2 receptors in this
      disease. OBJECTIVE: We hypothesized that profiles of E-prostanoid (EP) receptor
      expression are altered on asthmatic bronchial inflammatory cells in vivo and
      further altered by allergen challenge in vivo and proinflammatory mediators in
      vitro. METHODS: The numbers and phenotypes of EP 1-4 immunoreactive induced
      sputum cells from atopic asthmatics (n = 13; before and 24 hours after allergen
      inhalational challenge) and normal controls (n = 9; 3 after saline challenge) and
      EP 1-4 expression on purified blood eosinophils from both groups (n = 4 for each)
      before and after stimulation with LPS and/or IL-5 in vitro were measured by using
      single and double immunocytochemistry. RESULTS: Subsets of sputum cells of all
      phenotypes expressed all 4 EP receptors in both patients with asthma and
      controls. There were significantly greater numbers of macrophages expressing all
      4 EP receptors and increased percentages of macrophages expressing EP 2 and EP 4
      in patients with asthma compared with controls. Allergen bronchial challenge of
      patients with asthma was associated with a selective influx of eosinophils, but
      the percentages of these and other leukocytes expressing all 4 EP receptors were
      unchanged. Compared with sputum, only small percentages of peripheral blood
      eosinophils expressed each receptor, but this was increased by culture with
      exogenous IL-5 or LPS. CONCLUSION: E-prostanoid receptor expression is increased
      on airway macrophages of patients with asthma at baseline and may be altered on
      eosinophils after allergen challenge in vivo in response to inflammatory stimuli.

PMID- 15577829
TI  - Loss of syk kinase during IgE-mediated stimulation of human basophils.
AB  - BACKGROUND: Ongoing secretion from human basophils is a balance of activation and
      deactivation events. Recent studies have focused on downregulatory steps that
      appear to modify the presence of the activated state of various signaling
      molecules. We now examine downregulation regulated by mechanisms related to
      proteasome processing. OBJECTIVE: To determine the long-term effects of
      FcepsilonRI aggregation on expression of syk kinase. METHODS: Peripheral blood
      basophils were examined for changes in the expression of syk kinase after
      stimulation with optimal and suboptimal stimulation. RESULTS: Stimulation results
      in a 20% loss of syk in 1 hour and an 80% loss of syk in longer incubations (>18
      hours). Loss of syk in this time frame can occur at levels of stimulation that do
      not result in observable mediator release. Loss of syk occurs after stimulation
      with either anti-IgE antibody or antigen. Activation is shown to result in c-Cbl
      phosphorylation, and its association with syk and immunoblotting reveals the
      appearance of a ladder of syk species with molecular weights that are consistent
      with ubiquitylation of syk. Stimulation in the presence of a proteasome inhibitor
      such as lactacystin A results in the sustained presence of very high-molecular
      weight ubiquitylated species, although it does not alter the presence of the syk
      ladder. CONCLUSIONS: Although the loss of syk is probably too slow to account for
      downregulation of ongoing secretion of histamine or leukotriene C4 release, it
      may lead to longer-term alterations in basophil function that explain
      characteristics of clinical procedures like rapid drug desensitization.

PMID- 15577830
TI  - Inhalation of low-dose endotoxin favors local T(H)2 response and primes airway
      phagocytes in vivo.
AB  - BACKGROUND: We previously reported that inhalation of 5 mug of endotoxin (30,000
      endotoxin units [EU]) induced airway neutrophilia and decreased phagocytosis by
      airway monocytes, macrophages, and neutrophils. Conversely, we recently reported
      that very low doses of endotoxin, which are not associated with neutrophil
      influx, enhance response to allergen in the nasal and bronchial airway.
      OBJECTIVE: We sought to determine whether endotoxin (0-10,000 EU) at doses that
      do not induce airway neutrophilia prime airway phagocyte function, alter
      expression of relevant cell-surface receptors (membrane-bound CD14 [mCD14] and
      CD11b/CR3), and cause induction of a T(H)2 cytokine profile in the airway.
      METHODS: Thirteen nonallergic healthy volunteers were challenged on separate
      occasions with escalating doses of Clinical Center Reference Endotoxin (CCRE; 0,
      2500, 5000, and 10,000 EU), with 9 volunteers completing the entire dose range.
      Sputum cells and fluid-phase components were recovered 6 hours after challenge.
      Sputum inflammatory cells were analyzed by means of flow cytometry for mCD14 and
      CD11b expression and immune function (phagocytosis of IgG-opsonized zymosan
      particles). RESULTS: At all doses of CCRE, there was no increase in airway
      neutrophils relative to that caused by saline. However, inhalation of 10,000 EU
      enhanced phagocytosis (monocytes and macrophages), upregulated expression of
      CD11b and mCD14 (monocytes and neutrophils), and increased IL-13 levels, whereas
      IFN-gamma levels were significantly decreased. CONCLUSION: The 10,000-EU dose of
      CCRE is subthreshold for inducing airway neutrophilia but primes phagocyte
      function and cell-surface receptor expression in the presence of increased IL-13
      and decreased IFN-gamma levels. We speculate that low-dose endotoxin challenge
      skews airway inflammation in a T(H)2 direction in vivo .

PMID- 15577831
TI  - Asthma is induced by intranasal coadministration of allergen and natural killer T
      cell ligand in a mouse model.
AB  - BACKGROUND: Allergic asthma is an inflammatory lung disease caused by a T(H)2
      driven immune response. However, intranasal exposures to soluble antigen lead to
      mucosal tolerance, and the mechanism involved in generation of T(H)2 responses to
      inert inhaled allergens is unknown. OBJECTIVE: The aim of this study was to
      investigate whether CD1d-restricted natural killer T (NKT) cells can contribute
      to the induction of T(H)2-dependent allergic asthma in a mouse model. METHODS: To
      investigate the effect of NKT cells on the development of asthma, NKT cell
      ligand, alpha-galactosylceramide (alphaGC), was used with antigens. We
      intranasally sensitized Balb/c mice with various combinations of antigen and
      alphaGC for 3 consecutive days and challenged them 2 weeks later with an aerosol
      of ovalbumin. NKT cell-deficient or T(H) cell-deficient mice were immunized by
      administering ovalbumin and alphaGC together, and ovalbumin inhalation. RESULTS:
      Only when immunized with ovalbumin plus alphaGC, airway hyperreactivity, airway
      eosinophils, elevated IgE level, and T(H)2-cytokine production were observed in
      Balb/c mice. Ovalbumin alone, alphaGC alone, or BSA plus alphaGC-immunized mice
      did not induce asthma. Studies in NKT cell-deficient, or CD4(+) T-cell-deficient
      mice intranasally exposed to ovalbumin plus alphaGC did not show the development
      of asthma. An increase of NKT cells in bronchoalveolar lavage was observed in the
      pathologic states. CONCLUSION: These data demonstrate that NKT cells can play
      crucial roles in allergen sensitization and pathologic states in asthma.
      Furthermore, our new asthma model using alphaGC will be very useful to induce
      asthma and to dissect the role of NKT cells and other cells in asthma.

PMID- 15577832
TI  - Dose dependence and time course of the immunologic response to administration of
      standardized cat allergen extract.
AB  - BACKGROUND: The immunologic response to allergen immunotherapy with 3 serial 5
      fold doses of cat extract has been studied after approximately 5 weeks of
      immunotherapy. The highest dose containing 15 mug of Fel d 1 produced the most
      consistent and favorable response. It is unknown whether the comparative response
      on reaching a maintenance dose is maintained with long-term maintenance therapy.
      OBJECTIVE: The purpose of this investigation was to evaluate the immunologic
      responses with these 3 serial doses of cat hair and dander extract at baseline,
      after reaching the maintenance dose (approximately 5 weeks), and after 1 year of
      maintenance immunotherapy. METHODS: Twenty-eight patients with cat allergy
      randomized in a double-blind study were assigned to one of 4 treatment groups:
      placebo or cat hair and dander extract containing 0.6 mug of Fel d 1, 3 mug of
      Fel d 1, and 15 mug of Fel d 1 at maintenance. Studies included skin prick tests
      and late cutaneous reactions with cat hair and dander extract, titrated nasal
      challenges with the extract, serum cat allergen-specific IgG4 and IgE
      measurement, and flow cytometric and ELISA analysis of whole blood and intranasal
      cytokines (TGF-beta, IL-10, IFN-gamma, IL-4, and IL-5). RESULTS: Twenty-six
      subjects completed the study. After both 5 weeks and 1 year, significant and dose
      dependent differences were seen with total symptom scores on nasal challenge ( P
      < .0001), with titrated skin prick testing with cat dander extract at 5 weeks ( P
      = .014) and 1 year ( P < .0001), and with cat-specific IgG4 measurement at 5
      weeks ( P = .004) and 1 year ( P = .003). At 1 year, neither flow cytometry of
      whole blood nor ELISA evaluation of nasal cytokines demonstrated any significant
      differences among the treatment groups. CONCLUSION: The response to titrated
      nasal allergen challenge, titrated skin prick testing, and allergen-specific IgG4
      measurement to cat immunotherapy at 5 weeks is predictive of the response at 1
      year.

PMID- 15577833
TI  - CD8+ alphabeta T cells can mediate late airway responses and airway eosinophilia
      in rats.
AB  - BACKGROUND: The function of CD8+ T-cell subsets in mediating late allergic
      responses is incompletely understood. OBJECTIVE: We sought to test the hypothesis
      that CD8+ alphabeta T cells are proinflammatory in the airways in vivo by using a
      well-characterized animal model and the technique of adoptive transfer. METHODS:
      Brown Norway rats were administered CD8 + alphabeta T cells (10 6 )
      intraperitoneally purified from lymph node cells of either naive or ovalbumin
      (OVA)-sensitized rats and were challenged with aerosolized OVA 2 days later.
      Control rats were sensitized to 100 mug of OVA in Al(OH) 3 subcutaneously or sham
      sensitized to saline and were OVA challenged 2 weeks later. RESULTS: The OVA
      sensitized and OVA-challenged group and the recipients of OVA-primed CD8+
      alphabeta T cells had significant late airway responses calculated from lung
      resistance measured for an 8-hour period after challenge compared with the naive
      CD8 + alphabeta T cell-transferred group and the sham-sensitized control group.
      The number of eosinophils in bronchoalveolar lavage fluid increased in the OVA
      sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared
      with numbers in the naive CD8+ alphabeta T-cell recipients and the sham
      sensitized control group. IL-4 and IL-5 cytokine mRNA expression in
      bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA
      primed CD8+ alphabeta T-cell recipients compared with that in the sham-sensitized
      group. CONCLUSION: We conclude that antigen-primed CD8 + alphabeta T cells might
      have a proinflammatory role in allergen-driven airway responses in the rat.

PMID- 15577834
TI  - Urinary eicosanoid and tyrosine derivative concentrations in patients with
      vasculitides.
AB  - BACKGROUND: Vasculitides are classified on the basis of the type of cell
      involved, namely, eosinophilic vasculitides such as Churg-Strauss syndrome (CSS)
      and noneosinophilic vasculitides. However, knowledge on inflammatory mediators
      and oxidative tissue damage associated with vasculitides is insufficient.
      OBJECTIVE: We measured the urinary concentrations of inflammatory mediators and
      tyrosine derivatives to assess biomarkers associated with the pathophysiology of
      vasculitides. METHODS: Urine was collected from 9 patients with CSS during acute
      exacerbation and during clinical remission, 24 patients with rheumatoid arthritis
      in stable condition, and 8 patients with vasculitis diseases (VDs) during acute
      exacerbation. Leukotriene E 4 (LTE 4 ), 9alpha,11beta prostaglandin F 2 , and
      eosinophil-derived neurotoxin (EDN) concentrations were determined by enzyme
      immunoassay. 3-Bromotyrosine (BrY) and 3-chlorotyrosine (ClY) concentrations were
      determined by gas chromatography-mass spectrometry. RESULTS: The urinary LTE 4 ,
      EDN, BrY, and ClY concentrations were significantly higher in the patients with
      CSS during acute exacerbation than in healthy control subjects and, except for
      urinary ClY concentration, significantly decreased during clinical remission. The
      urinary EDN and BrY concentrations were significantly higher in patients with CSS
      during acute exacerbation than in patients with VD during acute exacerbation.
      Only urinary LTE 4 concentration was significantly different between the patients
      with rheumatoid arthritis in stable condition and the patients with VD during
      acute exacerbation. CONCLUSION: Oxidative tissue damage caused by eosinophil
      peroxidase is a pathophysiological characteristic of eosinophil-associated
      diseases such as CSS. Urinary LTE 4 concentration may reflect a
      pathophysiological event involved in eosinophilic and noneosinophilic
      vasculitides. Cysteinyl-leukotriene pathways are potential therapeutic targets
      for small-vessel vasculitides.

PMID- 15577835
TI  - Chronic sinusitis consensus and the way forward.

PMID- 15577836
TI  - M cell targeting with Aleuria aurantia lectin as a novel approach for oral
      allergen immunotherapy.
AB  - BACKGROUND: The extent and quality of the immune response to orally applied
      allergens may critically depend on the precise site of uptake at the intestinal
      mucosa. OBJECTIVE: The aim of this study was to construct allergen vehicles
      optimized for oral allergen immunotherapy. METHODS: By using a murine model, we
      examined the immunomodulatory effect of birch pollen proteins entrapped in
      poly(D,L-lactide-co-glycolide) microspheres, which were specifically targeted to
      enterocytes or to M cells, in an ongoing T h 2 response. BALB/c mice express
      different carbohydrates on these 2 cell types. To target the sialylic residues on
      murine enterocytes, we functionalized microspheres with wheat germ agglutinin
      (WGA) and, to target alpha-L-fucose on M cells, with a lectin from Aleuria
      aurantia (AAL), the orange peel mushroom. RESULTS: Both WGA and AAL
      functionalization enhanced binding to human Caco2 cells substantially, which
      express sialylic and, as carcinoma cells, also alpha-L-fucose residues. Different
      groups of BALB/c mice were first sensitized to birch pollen and subsequently fed
      with birch pollen-loaded functionalized (WGA microspheres, AAL microspheres) or
      nonfunctionalized, birch pollen extract-loaded particles. When mice were fed with
      AAL microspheres, birch pollen-specific IgG2a, but not IgG1 or IgE, increased
      significantly. As expected, in a 3 H-thymidin assay, their splenocytes
      proliferated specifically on birch pollen stimulation. Both targeting strategies,
      using WGA or AAL, induced IL-10 as well as IL-4 production. However, in AAL
      microsphere-treated mice, IFN-gamma synthesis was significantly increased, which
      may be responsible for the significant IgG2a production in this group.
      CONCLUSION: Our data indicate that targeting M cells by using AAL-coated allergen
      vehicles may be a promising strategy for oral allergen immunotherapy.

PMID- 15577837
TI  - Chronic rhinosinusitis: an enhanced immune response to ubiquitous airborne fungi.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common long-term
      illnesses in the United States. The etiology of CRS is unknown, and no effective
      treatment has been established. OBJECTIVE: We investigated the hypothesis that
      abnormal immunologic responses to ubiquitous airborne fungi contribute to the
      pathogenesis of this disease. METHODS: The proliferative and cytokine responses
      of PBMCs to extracts from 4 common airborne fungi-including Alternaria ,
      Aspergillus , Cladosporium , and Penicillium -were examined by in vitro culture.
      Serum specimens were tested for specific IgE and IgG to these fungi. RESULTS:
      PBMCs from approximately 90% of the patients with CRS, but not those from normal
      individuals, produced both IL-5 and IL-13 when exposed to Alternaria.
      Furthermore, PBMCs from patients with CRS produced significantly more IFN-gamma
      than PBMCs from normal individuals in response to Alternaria (median, 553 pg/mL
      vs 98 pg/mL; P < .01). Levels of serum IgG antibodies to Alternaria and
      Cladosporium were clearly increased in patients with CRS compared with normal
      individuals ( P < .01). Less than 30% of the patients with CRS had specific IgE
      antibodies to Alternaria or Cladosporium. The increased humoral (serum IgG)
      response strongly correlated with the increased cellular (IL-5 production)
      response to Alternaria ( r = 0.619; P < .01). CONCLUSION: Patients with CRS show
      exaggerated humoral and cellular responses, both T(H)1 and T(H)2 types, to common
      airborne fungi, particularly Alternaria. The anomalous immune and inflammatory
      responses to ubiquitous fungi may explain the chronicity of airway inflammation
      in CRS.

PMID- 15577839
TI  - HLA-DQB1 *03 in allergic fungal sinusitis and other chronic hypertrophic
      rhinosinusitis disorders.
AB  - BACKGROUND: Many common chronic inflammatory disorders have strong HLA gene
      associations, particularly with MHC class II. Allergic fungal rhinosinusitis
      (AFS) and hypertrophic sinus disease (HSD) are chronic sinonasal mucosal
      inflammatory disorders. Allergic bronchopulmonary aspergillosis, a disorder
      analogous to AFS, was recently reported to have HLA-MHC class II associations.
      OBJECTIVE: We sought to determine whether MHC class II is also associated with
      AFS and HSD. METHODS: HLA DNA genotyping was obtained on 44 patients with AFS and
      30 patients with HSD (of which 21 were atopic). RESULTS: Sixty-six percent of
      patients with AFS carried at least one HLA-DQB1 *03 allele; DQB1 *0301 and DQB1
      *0302 were the most frequent allelic variants (odds ratio [OR] vs healthy
      subjects = 8.22; 95% CI, 4.30-15.73; P < .001; OR vs all patients with HSD =
      1.93; 95% CI, 1.09-3.41; P < .01; OR vs atopic patients with HSD = 2.57; 95% CI,
      1.46-4.53; P < .001). Of the 31 patients with AFS and positive Bipolaris
      spicifera cultures, 68% had DQB1 *03, with DQB1 *0301 and DQB1 *0302 being most
      frequent (OR vs healthy subjects = 8.93; 95% CI, 4.65-17.15; P < .001; OR vs
      patients with HSD = 2.10; 95% CI, 1.18-3.73; P < .001). Of the 30 patients with
      HSD, 50% carried DQB1 *03 (OR vs healthy subjects = 4.25; 95% CI, 2.25-8.02; P <
      .001) but differed in frequencies of DQB1 *03 allelic variants compared with
      patients with AFS ( P = .0004). For HSD, nonatopic subjects had the highest DQB1
      *03 association (OR vs healthy subjects = 8.63; 95% CI, 4.50-16.54; P < .001).
      DQB1 *03 allelic variants did not correlate with allergy skin test results,
      atopic status, total serum IgE levels, culture results, asthma, or aspirin
      nonsteroidal anti-inflammatory drug hypersensitivity. CONCLUSION: Patients with
      AFS and HSD have HLA-DQB1 *03 alleles as a risk factor for disease, with AFS
      having the highest association. However, they differ in DQB1 *03 allelic variant
      frequencies, suggesting several potential roles for MHC class II in their
      immunopathogenesis.

PMID- 15577841
TI  - Remission of allergic rhinitis: An 8-year observational study.
AB  - BACKGROUND: Allergic rhinitis (AR) and sensitization are considered chronic
      conditions. However, few studies have reported remission rates in adults.
      OBJECTIVE: We sought to estimate the incidence of remission of AR during an 8
      year period. METHODS: Participants in a population-based study of 15- to 69-year
      old patients in 1990 were invited to a follow-up in 1998. Questionnaires on
      respiratory symptoms and serum for specific IgE (s-IgE) analyses were collected
      at both visits in 734 subjects (69% of those invited). Pollen AR was defined as
      rhinitis symptoms on pollen exposure within the last 12 months and s-IgE levels
      of class 2 or greater against pollen (birch, grass, or mugwort). This was similar
      for AR to animals (cat or dog) or house dust mites (HDMs). Remission of AR was
      defined as AR at baseline but no rhinitis symptoms at follow-up and sensitization
      (s-IgE level class > or =2 at baseline and class <2 at follow-up). RESULTS:
      Remission of AR occurred in 12% (pollen AR), 19% (animal AR), and 38% (HDM AR;
      overall, 17%) and was predicted by low s-IgE levels. Age, sex, asthma, atopic
      predisposition, age at AR onset, and AR duration had no predictive value. A
      decrease in s-IgE level was observed in only 22% of remitting subjects yet was
      seen significantly more often than in nonremitting subjects (7.4%). Remission of
      sensitization occurred in 6% (HDM) to 11% (pollen-furry animal) and was predicted
      on the basis of low s-IgE levels (class 2) at baseline. CONCLUSION: Remission of
      AR symptoms was relatively infrequent, and remission of both symptoms and IgE
      sensitization was rare. The results underline the chronic nature of AR in
      adulthood.

PMID- 15577842
TI  - Asthma and sensitization in a community with low indoor allergen levels and low
      pet-keeping frequency.
AB  - BACKGROUND: Little is known about causes of asthma and sensitization in desert
      countries. OBJECTIVE: To investigate risk factors associated with asthma and
      sensitization in Kuwait. METHODS: One hundred sixty children (9-16 years) with
      physician-diagnosed asthma were recruited and matched (age, sex) with 303 healthy
      controls. Risk factors were assessed by questionnaires, determination of
      sensitization status (skin tests and IgE), and home allergen exposure (mite, cat,
      dog, cockroach; ELISA). RESULTS: Home allergen levels and frequency of pet
      ownership were very low (cat, 4.1%; dog, 1.5%). The risk of cat sensitization
      increased significantly among cat owners (odds ratio [OR], 3.53; 95% CI, 1.33
      9.41; P = .01), and in children with reported contact with cats during the first
      year of life (OR, 2.60; 95% CI, 1.17-5.80; P = .019). In the multivariate
      analysis, maternal atopy (OR, 1.77; 95% CI, 1.13-2.75; P = .01) and cat ownership
      (OR, 3.32; 95% CI, 1.19-9.25; P = .02) remained significant associates of cat
      sensitization. Current dog ownership significantly increased the risk of
      sensitization to dog (OR, 6.05; 95% CI, 1.33-27.54; P = .02). In the multivariate
      analysis, dog ownership remained the only significant associate of dog
      sensitization (OR, 6.02; 95% CI, 1.30-27.96; P = .02). Sensitization to
      Alternaria was the strongest independent associate of the asthma group. Family
      history of asthma, history of whooping cough, current cat ownership, and breast
      feeding <2 months were other significant and independent risk factors for asthma.
      CONCLUSIONS: Pet ownership markedly increased the risk of sensitization to pets.
      Despite low allergen exposure, the pattern of childhood asthma in Kuwait follows
      that described in Western communities (strong association with sensitization).

PMID- 15577843
TI  - Risk of severe allergic reactions from the use of potassium iodide for radiation
      emergencies.
AB  - Potassium iodide (KI) may be prescribed for widespread use in the event of a
      radiation emergency to prevent the uptake of radioactive iodide by the thyroid
      gland. The available literature was reviewed and expert opinion sought among
      members of the Adverse Reactions to Foods and the Adverse Reactions to Drugs and
      Biologicals Committees of the Academy to assemble evidenced-based conclusions
      regarding the risks of an allergic reaction to this therapy. This article
      describes the information leading to the following conclusions: (1) anaphylactoid
      reactions to radiocontrast media should not be considered evidence of KI allergy,
      (2) allergic contact dermatitis from iodine-containing antibacterial preparations
      should not be considered evidence of IgE antibody-mediated KI allergy or
      sensitivity, (3) IgE antibody-mediated allergy to seafood should not be
      considered evidence of KI allergy or sensitivity, and (4) physicians should
      ensure that persons are not allergic to inactive ingredients or components of the
      KI formulation prescribed.

PMID- 15577844
TI  - Serum nutrient markers and skin prick testing using data from the Third National
      Health and Nutrition Examination Survey.
AB  - BACKGROUND: Diet nutrients and allergic sensitization both affect the development
      and severity of asthma, but the interrelationship between oral intake and
      allergic sensitization is not well characterized, although previous work suggests
      that a higher vitamin E intake may be protective against allergic sensitization.
      OBJECTIVE: To determine whether serum levels of dietary antioxidants, lipids, and
      other nutrients are associated with the presence of allergen skin sensitization.
      METHODS: Cross-sectional logistic regression analysis of 30 serum nutrient levels
      in relation to 10 skin test allergens in adults and children in the Third
      National Health and Nutrition Survey. RESULTS: In adults, allergic skin
      sensitization was less common in participants with higher serum levels of vitamin
      E: the adjusted odds ratio (OR) per SD difference in vitamin E level was 0.93
      (95% CI, 0.87-0.99). Two of the carotenoids, beta-cryptoxanthin and alpha
      carotene, were also inversely associated with allergic skin sensitization (OR,
      0.89; 95% CI, 0.83-0.95; and OR, 0.95; 95% CI, 0.91-0.99, respectively). Among
      adults, serum lycopene had a positive association with allergen sensitization. In
      youths, however, vitamin A was associated with an increased risk, and high
      density lipoprotein cholesterol was associated with a decreased risk of allergic
      sensitization. The use of vitamin or mineral supplements had little effect on the
      magnitude of all reported associations. CONCLUSION: Overall, there were no strong
      or consistent associations between serum levels of potentially antiallergic
      nutrients, and the occurrence of allergic skin sensitization in these data.
      However limited, findings suggest that increases in vitamin E, carotenoids, and
      high-density lipoprotein cholesterol may reduce the risk of allergic skin
      sensitization.

PMID- 15577845
TI  - Prostaglandin E(2) suppresses CCL27 production through EP2 and EP3 receptors in
      human keratinocytes.
AB  - BACKGROUND: The chemokine CCL27 attracts skin-homing T cells. CCL27 production by
      keratinocytes is enhanced in skin lesions from patients with atopic dermatitis or
      psoriasis vulgaris. It is suggested that prostaglandin E(2) (PGE(2)) regulates
      skin inflammation. OBJECTIVE: We examined the in vitro effects of PGE(2) on CCL27
      production in human keratinocytes. METHODS: Keratinocytes were incubated with TNF
      alpha in the presence or absence of PGE(2) . CCL27 secretion and mRNA level were
      analyzed by means of ELISA and RT-PCR, respectively. Nuclear factor kappaB (NF
      kappaB)-dependent transcriptional activity was analyzed by using luciferase
      assays. RESULTS: TNF-alpha increased CCL27 secretion and mRNA levels in parallel
      to NF-kappaB activity in keratinocytes. NF-kappaB p50 or p65 antisense
      oligonucleotides suppressed TNF-alpha-induced CCL27 production, indicating the
      requirement of NF-kappaB for CCL27 production. PGE(2) , EP2, or EP3 agonists
      reduced TNF-alpha-induced CCL27 secretion and mRNA levels in parallel to NF
      kappaB activity and CCL2, CCL5, CXCL8, and CXCL10 mRNA levels. Either EP3
      specific or dual EP1-EP2 antagonist partially blocked the inhibitory effects of
      PGE(2) on CCL27 production and NF-kappaB activity, and the addition of both
      completely abrogated the inhibition, whereas EP1 or EP4 antagonists were
      ineffective. Intracellular Ca(2+) chelator BAPTA/AM or cyclic adenosine
      monophosphate (cAMP)-dependent protein kinase inhibitor H-89 partially blocked
      the inhibitory effects of PGE(2) on CCL27 production and NF-kappaB activity, and
      the addition of both completely abrogated the inhibition. PGE(2) or EP3 agonist
      increased intracellular Ca(2+) concentrations. PGE(2) or EP2 agonist increased
      intracellular cAMP concentrations. CONCLUSION: PGE(2) might suppress CCL27
      production by inhibiting NF-kappaB activity through EP2-mediated cAMP and EP3
      mediated Ca(2+) signals. PGE 2 might terminate T cell-mediated skin inflammation
      by inhibiting CCL27 production.

PMID- 15577846
TI  - Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in
      patients with combined birch pollen and peanut allergy.
AB  - BACKGROUND: We recently described patients with soybean allergy mainly mediated
      by cross-reactivity to birch pollen allergens. A majority of those patients were
      reported to have peanut allergy. OBJECTIVE: We sought to study the occurrence of
      peanut allergy in patients allergic to birch pollen and characterized the Bet v 1
      homologous peanut allergen Ara h 8. METHODS: Recombinant Ara h 8 was cloned with
      degenerated primers and expressed in Escherichia coli. Nine Swiss and 11 Dutch
      patients with peanut and birch pollen allergy and a positive double-blind,
      placebo-controlled food challenge result to peanut were investigated for IgE
      reactivity to birch pollen and purified peanut allergens and cross-reactivity
      between birch and peanut. Ara h 8 stability against digestion and roasting was
      assessed by means of RAST inhibition. The IgE cross-linking potency of Ara h 8
      was tested on the basis of basophil histamine release. RESULTS: During double
      blind, placebo-controlled food challenge, all patients experienced symptoms in
      the oral cavity, progressing to more severe symptoms in 40% of patients. CAP-FEIA
      detected recombinant (r) Ara h 8-specific IgE in 85%. IgE binding to Ara h 8 was
      inhibited by Bet v 1 in peanut extract immunoblotting and in RAST inhibition. In
      EAST inhibition recombinant rAra h 8 inhibited IgE binding to peanut in 4 of 7
      tested patient sera. Antipeanut response was dominated by Ara h 8 in 12 of 17
      tested patients. Furthermore, our results demonstrate a low stability of Ara h 8
      to roasting and no stability to gastric digestion. Basophil histamine release
      with rAra h 8 was more than 20% in 5 of 7 tested sera. CONCLUSIONS: Peanut
      allergy might be mediated in a subgroup of our patients by means of cross
      reaction of Bet v 1 with the homologous peanut allergen Ara h 8.

PMID- 15577847
TI  - Invasive infection with Trichosporon inkin in 2 siblings with chronic
      granulomatous disease.
AB  - A 9-year-old girl with autosomal recessive chronic granulomatous disease (CGD)
      presented with asymptomatic bilateral pulmonary infiltrates on routine computed
      tomography. Fine-needle aspirate of the infiltrates was obtained and showed
      fungal cells resembling Trichosporon inkin . The specimen grew in culture, and
      testing by means of both API 20C and PCR amplification confirmed the diagnosis of
      T inkin . The infiltrates increased in size, despite sequential therapy with
      voriconazole, liposomal amphotericin B, caspofungin, and posaconazole. The
      patient required resection of the infected lung tissue, after which she recovered
      completely. While she was undergoing therapy, her 13-year-old brother, also with
      CGD, was given a diagnosis of bilateral T inkin -induced pulmonary infection. He
      also required bilateral pulmonary resection for cure. These cases demonstrate the
      predisposition of patients with CGD to have invasive infections with unusual
      fungal organisms, such as T inkin . They also illustrate the difficulty of
      treating invasive T inkin infections with antifungal agents alone. There are 9
      previously reported cases of invasive infections caused by T inkin , 3 of which
      are in patients with CGD. All patients required removal of infected prosthetic
      devices or surgical resection of infected tissue for cure.

PMID- 15577848
TI  - Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma.
AB  - BACKGROUND: T regulatory (T reg ) cells are characterized by expression of
      suppressive cytokines and the transcription factor FOXP3. They play a key role in
      balancing immune responses and maintain peripheral tolerance against antigens and
      allergens. The loss of peripheral tolerance against allergens causes diseases
      that can be therapeutically controlled with glucocorticoids. OBJECTIVE: The
      present study investigates whether glucocorticoids affect the activity of T reg
      cells on the basis of FOXP3 and cytokine expression. METHODS: CD4 + T cells from
      healthy donors and glucocorticoid-treated asthmatic patients were isolated, and
      expression of FOXP3, along with IL-10 and TGF-beta1, was determined. The effect
      of glucocorticoids on T reg cells was measured in vivo before and after GC
      treatment and in in vitro cultures. RESULTS: FOXP3 mRNA expression was
      significantly increased in asthmatic patients receiving inhaled glucocorticoid
      treatment, systemic glucocorticoid treatment, or both. FOXP3 tightly correlated
      with IL10 mRNA expression. No correlation of FOXP3 mRNA expression was observed
      in relation to a (GT)n microsatellite promoter polymorphism on chromosome Xp11.23
      or total IgE level. The frequency of CD25 + memory CD4 + T cells and transient
      FOXP3 mRNA expression by CD4 + T cells significantly increased after systemic
      glucocorticoid treatment, whereas TGFB1 expression did not change. Furthermore,
      glucocorticoids induced IL10 and FOXP3 expression in short-term and long-term
      cultures in vitro. CONCLUSION: These findings demonstrate that glucocorticoid
      treatment is not only immunosuppressive and anti-inflammatory but also promotes
      or initiates differentiation toward T R 1 cells by a FOXP3-dependent mechanism.
      Strategies that convert transient glucocorticoid-induced T reg activity into a
      stable phenotype might improve allergy and asthma therapy.

PMID- 15577849
TI  - Cytomegalovirus infection and development of allergic diseases in early
      childhood: interaction with EBV infection?
AB  - BACKGROUND: Chronic replication of cytomegalovirus and EBV in early life may
      affect the immune system and play a role in the development of allergy in
      children. OBJECTIVE: To assess the relation between cytomegalovirus infection and
      allergic disorders in children, including a possible interaction with EBV
      infection. METHODS: From a prospective birth cohort study in Stockholm, on
      factors of importance for development of allergy, 2581 four-year-old children
      were enrolled. The classification of allergic diseases was based on questionnaire
      answers and determination of IgE antibodies to common airborne and food
      allergens. IgG to cytomegalovirus was determined by a commercial ELISA and to EBV
      by indirect immunofluorescence. RESULTS: A total of 1191 (46%) children were
      cytomegalovirus-seropositive. There were no significant associations between
      seropositivity to cytomegalovirus and allergic manifestations, such as bronchial
      asthma, suspected allergic rhinitis, or atopic dermatitis. Seropositivity to
      cytomegalovirus alone, ie, without seropositivity to EBV, was related to IgE
      antibodies to airborne and food allergens (adjusted odds ratio, 1.8; 95% CI, 1.2
      2.9). An antagonism between cytomegalovirus and EBV in relation to sensitization
      to airborne and food allergens was suggested ( P = .05). CONCLUSION: The study
      does not support the hypothesis that previous cytomegalovirus infection plays an
      important role in the pathogenesis of bronchial asthma, suspected allergic
      rhinitis, or atopic dermatitis in children. However, in the absence of EBV
      infection, cytomegalovirus infection may be related to sensitization to airborne
      and food allergens.

PMID- 15577850
TI  - Susceptibility to allergic lung disease regulated by recall responses of dual
      receptor memory T cells.
AB  - BACKGROUND: Microbial infections are associated with the initial susceptibility
      to and flares of asthma. However, immunologic mechanisms whereby infections might
      alter the asthmatic phenotype are lacking. OBJECTIVE: To test the hypothesis that
      memory T cells specific both for a viral antigen and an allergen could influence
      the pathogenesis of allergic disease in vivo . METHODS: We developed a system in
      which 2 distinct T-cell receptors coexist on the T-cell surface, 1 specific for a
      virus and the other for an inhaled antigen. RESULTS: We show that a population of
      dual-receptor T cells, polarized through a virus-specific T-cell receptor to
      contain T(H)1 or T(H)2 cells, can be reactivated through an unrelated T-cell
      receptor in recall responses in vivo . Quiescent memory cells derived from a
      T(H)1-polarized effector population blocked the development of airway
      hyperreactivity in a model of allergic lung disease, in association with
      decreased induction of chemokines and eosinophil recruitment. Conversely,
      reactivation of quiescent T(H)2 cells after inhalation of antigen or virus
      infection was sufficient to lead to the development of airway hyperresponsiveness
      and allergic pulmonary inflammation in mice whose lungs were previously normal.
      CONCLUSION: These data provide evidence that dual-receptor memory T cells can
      regulate allergic disease susceptibility and suggest that they may play a role in
      mediating the influence of microbes on asthma pathogenesis.

PMID- 15577851
TI  - Rebound eosinophilia after treatment of hypereosinophilic syndrome and
      eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700.
AB  - BACKGROUND: Hypereosinophilic syndrome and eosinophilic gastroenteritis with
      peripheral eosinophilia are characterized by sustained eosinophilia and
      eosinophil-mediated tissue damage. Although treatment with the humanized
      monoclonal anti-IL-5 antibody SCH55700 resulted in improvement of eosinophilia
      and clinical symptoms in 6 of 8 of patients with hypereosinophilic syndrome or
      eosinophilic gastroenteritis with peripheral eosinophilia for as long as 12
      weeks, eosinophil counts subsequently rose above baseline levels, accompanied by
      an exacerbation of symptoms. OBJECTIVE: To identify the mechanism underlying this
      rebound eosinophilia. METHODS: Purified eosinophils from patients or normal
      donors were cultured with IL-5, patient serum, and/or anticytokine antibodies,
      and eosinophil survival was assessed by flow cytometry. Serum and intracellular
      cytokine levels were measured by multiplex sandwich ELISA and flow cytometry,
      respectively. RESULTS: Before treatment with SCH55700, in vitro eosinophil
      survival in media and in response to recombinant IL-5 was similar in patients and
      normal donors. At 1 month posttreatment, the eosinophil survival curves were
      unchanged in 4 of 5 patients in media and in all 5 patients in response to
      recombinant IL-5. Normal eosinophil survival was prolonged in cultures containing
      posttreatment but not pretreatment sera (pretreatment vs posttreatment, 10.74% vs
      73.02% live cells; P = .01). This posttreatment serum effect on eosinophil
      survival was reversed by the addition of the monoclonal anti-IL-5 antibody TRFK5.
      Although increased levels of serum IL-5 were observed at 1 month compared with 2
      to 3 days posttreatment in 5 of 6 patients ( P = .04), intracellular cytokine
      analysis did not reveal increased production of IL-5 by peripheral blood
      mononuclear cells. CONCLUSIONS: The rebound eosinophilia after SCH55700 treatment
      is a result of a serum factor that enhances eosinophil survival. Reversal of this
      effect by the addition of antibody to IL-5 suggests that this factor may be IL-5
      itself.

PMID- 15577852
TI  - Nuclear factor kappaB essential modulator-deficient child with immunodeficiency
      yet without anhidrotic ectodermal dysplasia.
AB  - BACKGROUND: Amorphic mutations in the X-linked nuclear factor kappaB essential
      modulator ( NEMO ) gene cause Incontinentia pigmenti, which is lethal in
      hemizygous male patients. Hypomorphic NEMO mutations in male patients lead to
      anhidrotic ectodermal dysplasia (EDA) with immunodeficiency. OBJECTIVE: To report
      the clinical features of a child bearing a NEMO mutation who displayed an
      immunodeficiency without EDA. METHODS: Documentation of clinical care, chart
      review, standard immunologic and microbiological laboratory techniques, mutation
      analysis of the NEMO gene. RESULTS: Since the age of 15 months, the patient had
      Mycobacterium avium disease, beginning with multiple adenitis, later followed by
      disseminated osteomyelitis and dermatitis. In addition, Haemophilus influenzae
      and Streptococcus pneumoniae infections led to bronchiectasis. An immunologic
      work-up revealed a low production of IFN-gamma by PBMCs associated with a hyper
      IgM phenotype. Despite treatment using repeated cycles of a 4-drug
      antimycobacterial regimen, continuous subcutaneous IFN-gamma, repeated antibiotic
      treatment, and intravenous immunoglobulin substitution, the boy remained
      chronically ill. At the age of 12 years, the disease was complicated by severe
      autoimmune hemolytic anemia and eventually fatal herpes simplex virus 1
      encephalitis despite high-dose acyclovir therapy. Although he did not present any
      sign of EDA, a novel type of disease-causing hypomorphic NEMO mutation (110
      111insC in exon 2) was identified. CONCLUSION: This case demonstrates that
      patients hemizygous for NEMO mutations can present with an immunodeficiency
      without EDA. An investigation of NEMO should thus be undertaken in selected
      children with immunodeficiency despite the lack of EDA.

PMID- 15577853
TI  - Increased noncanonical splicing of autoantigen transcripts provides the
      structural basis for expression of untolerized epitopes.
AB  - BACKGROUND: Alternative splicing is important for increasing the complexity of
      the human proteome from a limited genome. Previous studies have shown that for
      some autoantigens, there is differential immunogenicity among alternatively
      spliced isoforms. OBJECTIVES: Herein, we tested the hypothesis that alternative
      splicing is a common feature for transcripts of autologous proteins that are
      autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts
      have a lower frequency of alternative splicing. METHODS: The extent of
      alternative splicing within 45 randomly selected self-proteins associated with
      autoimmune diseases was compared with 9554 randomly selected proteins in the
      human genome by using bioinformatics analyses. Isoform-specific regions that
      resulted from alternative splicing were studied for their potential to be
      epitopes for antibodies or T-cell receptors. RESULTS: Alternative splicing
      occurred in 100% of the autoantigen transcripts. This was significantly higher
      than the approximately 42% rate of alternative splicing observed in the 9554
      randomly selected human gene transcripts ( P < .001). Within the isoform-specific
      regions of the autoantigens, 92% and 88% encoded MHC class I and class II
      restricted T-cell antigen epitopes, respectively, and 70% encoded antibody
      binding domains. Furthermore, 80% of the autoantigen transcripts underwent
      noncanonical alternative splicing, which is also significantly higher than the
      less than 1% rate in randomly selected gene transcripts ( P < .001). CONCLUSION:
      These studies suggest that noncanonical alternative splicing may be an important
      mechanism for the generation of untolerized epitopes that may lead to
      autoimmunity. Furthermore, the product of a transcript that does not undergo
      alternative splicing is unlikely to be a target antigen in autoimmunity.

PMID- 15577854
TI  - Transient postviral vocal cord dysfunction.

PMID- 15577855
TI  - Loss of receptors and IgE in vivo during treatment with anti-IgE antibody.

PMID- 15577856
TI  - Method of nebulizer calibration and methacholine airway responsiveness.

PMID- 15577857
TI  - Glucocorticoid receptor alpha:beta ratio in blood mononuclear cells is reduced in
      cigarette smokers.

PMID- 15577859
TI  - Inflammation and remodeling in chronic obstructive pulmonary disease.

PMID- 15577865
TI  - Rhinosinusitis: establishing definitions for clinical research and patient care.

PMID- 15577866
TI  - The e-developing world.

PMID- 15577867
TI  - Suppressed study raises spectre of flawed drug regulation in US.

PMID- 15577868
TI  - Scientists decry 'spy' verdict for Russian physicist.

PMID- 15577869
TI  - Europe breaks ranks over fusion project site.

PMID- 15577870
TI  - Nuclear agreement paves way for fuel recycling in Japan.

PMID- 15577871
TI  - Plans to track tuna canned amid claims of cash shortfall.

PMID- 15577872
TI  - Canada pledges cash for more victims of blood-bank debacle.

PMID- 15577873
TI  - Croats protest that science minister is 'meddling' in MedILS.

PMID- 15577874
TI  - Geneticists prepare for deluge of mutant mice.

PMID- 15577876
TI  - Dispatches from the front line.

PMID- 15577877
TI  - David versus Goliath.

PMID- 15577879
TI  - Grade inflation keeps the customers happy.

PMID- 15577878
TI  - Journals must cooperate to defend biosecurity.

PMID- 15577880
TI  - Grade inflation: students seek it, funders reward it.

PMID- 15577881
TI  - Tackling grade inflation in US universities.

PMID- 15577882
TI  - The blame game.

PMID- 15577889
TI  - Wee beasties.

PMID- 15577890
TI  - Climate change: hot news from summer 2003.

PMID- 15577891
TI  - Information science: quantum errors corrected.

PMID- 15577893
TI  - Archaeology: greater expectations.

PMID- 15577894
TI  - Cytoskeleton: spindle saga.

PMID- 15577896
TI  - Cosmology: Neutrino probes of dark energy.

PMID- 15577895
TI  - Cell division: the heart of the cycle.

PMID- 15577897
TI  - Cell biology: clathrin's Achilles' ankle.

PMID- 15577899
TI  - Palaeobiology: Argentinian unhatched pterosaur fossil.
AB  - Our knowledge of the eggs and embryos of pterosaurs, the Mesozoic flying
      reptiles, is sparse. Until now, the recent discovery of an ornithocheirid embryo
      from 121-million-year-old rocks in China constituted the only reliable evidence
      of an unhatched pterosaur. Here we describe an embryonic fossil of a different
      pterosaur from the Early Cretaceous lacustrine deposits of Loma del Pterodaustro
      (the Lagarcito Formation, which is about 100 million years old) in central
      Argentina. This new fossil provides insight into the eggshell morphology, early
      growth and nesting environments of pterosaurs.

PMID- 15577900
TI  - Palaeontology: pterosaur egg with a leathery shell.
AB  - The recent discovery of a pterosaur egg with embryonic skeleton and soft tissues
      from the Yixian Formation confirmed that the flying pterosaurs were oviparous.
      Here we describe another pterosaur egg whose exquisite preservation indicates
      that the shell structure was soft and leathery.

PMID- 15577901
TI  - A synaptic laminin-calcium channel interaction organizes active zones in motor
      nerve terminals.
AB  - Synapse formation requires the differentiation of a functional nerve terminal
      opposite a specialized postsynaptic membrane. Here, we show that laminin beta2, a
      component of the synaptic cleft at the neuromuscular junction, binds directly to
      calcium channels that are required for neurotransmitter release from motor nerve
      terminals. This interaction leads to clustering of channels, which in turn
      recruit other presynaptic components. Perturbation of this interaction in vivo
      results in disassembly of neurotransmitter release sites, resembling defects
      previously observed in an autoimmune neuromuscular disorder, Lambert-Eaton
      myasthenic syndrome. These results identify an extracellular ligand of the
      voltage-gated calcium channel as well as a new laminin receptor. They also
      suggest a model for the development of nerve terminals, and provide clues to the
      pathogenesis of a synaptic disease.

PMID- 15577902
TI  - No cold dust within the supernova remnant Cassiopeia A.
AB  - A large amount (about three solar masses) of cold (18 K) dust in the prototypical
      type II supernova remnant Cassiopeia A was recently reported. It was concluded
      that dust production in type II supernovae can explain how the large quantities
      (approximately 10(8) solar masses) of dust observed in the most distant quasars
      could have been produced within only 700 million years after the Big Bang.
      Foreground clouds of interstellar material, however, complicate the
      interpretation of the earlier submillimetre observations of Cas A. Here we report
      far-infrared and molecular line observations that demonstrate that most of the
      detected submillimetre emission originates from interstellar dust in a molecular
      cloud complex located in the line of sight between the Earth and Cas A, and is
      therefore not associated with the remnant. The argument that type II supernovae
      produce copious amounts of dust is not supported by the case of Cas A, which
      previously appeared to provide the best evidence for this possibility.

PMID- 15577903
TI  - Stellar encounters as the origin of distant Solar System objects in highly
      eccentric orbits.
AB  - The Kuiper belt extends from the orbit of Neptune at 30 au to an abrupt outer
      edge about 50 au from the Sun. Beyond the edge is a sparse population of objects
      with large orbital eccentricities. Neptune shapes the dynamics of most Kuiper
      belt objects, but the recently discovered planet 2003 VB12 (Sedna) has an
      eccentric orbit with a perihelion distance of 70 au, far beyond Neptune's
      gravitational influence. Although influences from passing stars could have
      created the Kuiper belt's outer edge and could have scattered objects into large,
      eccentric orbits, no model currently explains the properties of Sedna. Here we
      show that a passing star probably scattered Sedna from the Kuiper belt into its
      observed orbit. The likelihood that a planet at 60-80 au can be scattered into
      Sedna's orbit is about 50 per cent; this estimate depends critically on the
      geometry of the fly-by. Even more interesting is the approximately 10 per cent
      chance that Sedna was captured from the outer disk of the passing star. Most
      captures have very high inclination orbits; detection of such objects would
      confirm the presence of extrasolar planets in our own Solar System.

PMID- 15577904
TI  - Realization of quantum error correction.
AB  - Scalable quantum computation and communication require error control to protect
      quantum information against unavoidable noise. Quantum error correction protects
      information stored in two-level quantum systems (qubits) by rectifying errors
      with operations conditioned on the measurement outcomes. Error-correction
      protocols have been implemented in nuclear magnetic resonance experiments, but
      the inherent limitations of this technique prevent its application to quantum
      information processing. Here we experimentally demonstrate quantum error
      correction using three beryllium atomic-ion qubits confined to a linear, multi
      zone trap. An encoded one-qubit state is protected against spin-flip errors by
      means of a three-qubit quantum error-correcting code. A primary ion qubit is
      prepared in an initial state, which is then encoded into an entangled state of
      three physical qubits (the primary and two ancilla qubits). Errors are induced
      simultaneously in all qubits at various rates. The encoded state is decoded back
      to the primary ion one-qubit state, making error information available on the
      ancilla ions, which are separated from the primary ion and measured. Finally, the
      primary qubit state is corrected on the basis of the ancillae measurement
      outcome. We verify error correction by comparing the corrected final state to the
      uncorrected state and to the initial state. In principle, the approach enables a
      quantum state to be maintained by means of repeated error correction, an
      important step towards scalable fault-tolerant quantum computation using trapped
      ions.

PMID- 15577905
TI  - Nonlinear optics in the extreme ultraviolet.
AB  - Nonlinear responses to an optical field are universal in nature but have been
      difficult to observe in the extreme ultraviolet (XUV) and soft X-ray regions
      owing to a lack of coherent intense light sources. High harmonic generation is a
      well-known nonlinear optical phenomenon and is now drawing much attention in
      attosecond pulse generation. For the application of high harmonics to nonlinear
      optics in the XUV and soft X-ray regime, optical pulses should have both large
      pulse energy and short pulse duration to achieve a high optical electric field.
      Here we show the generation of intense isolated pulses from a single harmonic
      (photon energy 27.9 eV) by using a sub-10-femtosecond blue laser pulse, producing
      a large dipole moment at the relatively low (ninth) harmonic order
      nonadiabatically. The XUV pulses with pulse durations of 950 attoseconds and 1.3
      femtoseconds were characterized by an autocorrelation technique, based on two
      photon above-threshold ionization of helium atoms. Because of the small cross
      section for above-threshold ionization, such an autocorrelation measurement of
      XUV pulses with photon energy larger than the ionization energy of helium has not
      hitherto been demonstrated. The technique can be extended to the characterization
      of higher harmonics at shorter wavelengths.

PMID- 15577906
TI  - Large fluctuations in speed on Greenland's Jakobshavn Isbrae glacier.
AB  - It is important to understand recent changes in the velocity of Greenland
      glaciers because the mass balance of the Greenland Ice Sheet is partly determined
      by the flow rates of these outlets. Jakobshavn Isbrae is Greenland's largest
      outlet glacier, draining about 6.5 per cent of the ice-sheet area, and it has
      been surveyed repeatedly since 1991 (ref. 2). Here we use remote sensing data to
      measure the velocity of Jakobshavn Isbrae between 1992 and 2003. We detect large
      variability of the velocity over time, including a slowing down from 6,700 m yr(
      1) in 1985 to 5,700 m yr(-1) in 1992, and a subsequent speeding up to 9,400 m yr(
      1) by 2000 and 12,600 m yr(-1) in 2003. These changes are consistent with earlier
      evidence for thickening of the glacier in the early 1990s and rapid thinning
      thereafter. Our observations indicate that fast-flowing glaciers can
      significantly alter ice discharge at sub-decadal timescales, with at least a
      potential to respond rapidly to a changing climate.

PMID- 15577907
TI  - Human contribution to the European heatwave of 2003.
AB  - The summer of 2003 was probably the hottest in Europe since at latest ad 1500,
      and unusually large numbers of heat-related deaths were reported in France,
      Germany and Italy. It is an ill-posed question whether the 2003 heatwave was
      caused, in a simple deterministic sense, by a modification of the external
      influences on climate--for example, increasing concentrations of greenhouse gases
      in the atmosphere--because almost any such weather event might have occurred by
      chance in an unmodified climate. However, it is possible to estimate by how much
      human activities may have increased the risk of the occurrence of such a
      heatwave. Here we use this conceptual framework to estimate the contribution of
      human-induced increases in atmospheric concentrations of greenhouse gases and
      other pollutants to the risk of the occurrence of unusually high mean summer
      temperatures throughout a large region of continental Europe. Using a threshold
      for mean summer temperature that was exceeded in 2003, but in no other year since
      the start of the instrumental record in 1851, we estimate it is very likely
      (confidence level >90%) that human influence has at least doubled the risk of a
      heatwave exceeding this threshold magnitude.

PMID- 15577908
TI  - Evidence for cultivar adoption and emerging complexity during the mid-Holocene in
      the La Plata basin.
AB  - Multidisciplinary investigations at the Los Ajos archaeological mound complex in
      the wetlands of southeastern Uruguay challenge the traditional view that the La
      Plata basin was inhabited by simple groups of hunters and gatherers for much of
      the pre-Hispanic era. Here we report new archaeological, palaeoecological and
      botanical data indicating that during an increasingly drier mid-Holocene, at
      around 4,190 radiocarbon (14C) years before present (bp), Los Ajos became a
      permanent circular plaza village, and its inhabitants adopted the earliest
      cultivars known in southern South America. The architectural plan of Los Ajos
      during the following Ceramic Mound Period (around 3,000-500 14C yr bp) is similar
      to, but earlier than, settlement patterns demonstrated in Amazonia, revealing a
      new and independent architectural tradition for South America.

PMID- 15577909
TI  - Trichomonas hydrogenosomes contain the NADH dehydrogenase module of mitochondrial
      complex I.
AB  - Hydrogenosomes are double-membraned ATP-producing and hydrogen-producing
      organelles of diverse anaerobic eukaryotes. In some versions of endosymbiotic
      theory they are suggested to be homologues of mitochondria, but alternative views
      suggest they arose from an anaerobic bacterium that was distinct from the
      mitochondrial endosymbiont. Here we show that the 51-kDa and 24-kDa subunits of
      the NADH dehydrogenase module in complex I, the first step in the mitochondrial
      respiratory chain, are active in hydrogenosomes of Trichomonas vaginalis. Like
      mitochondrial NADH dehydrogenase, the purified Trichomonas enzyme can reduce a
      variety of electron carriers including ubiquinone, but unlike the mitochondrial
      enzyme it can also reduce ferredoxin, the electron carrier used for hydrogen
      production. The presence of NADH dehydrogenase solves the long-standing conundrum
      of how hydrogenosomes regenerate NAD+ after malate oxidation. Phylogenetic
      analyses show that the Trichomonas 51-kDa homologue shares common ancestry with
      the mitochondrial enzyme. Recruitment of complex I subunits into a H2-producing
      pathway provides evidence that mitochondria and hydrogenosomes are aerobic and
      anaerobic homologues of the same endosymbiotically derived organelle.

PMID- 15577910
TI  - A candidate NAD+ transporter in an intracellular bacterial symbiont related to
      Chlamydiae.
AB  - Bacteria living within eukaryotic cells can be essential for the survival or
      reproduction of the host but in other cases are among the most successful
      pathogens. Environmental Chlamydiae, including strain UWE25, thrive as obligate
      intracellular symbionts within protozoa; are recently discovered relatives of
      major bacterial pathogens of humans; and also infect human cells. Genome analysis
      of UWE25 predicted that this symbiont is unable to synthesize the universal
      electron carrier nicotinamide adenine dinucleotide (NAD+). Compensation of
      limited biosynthetic capacity in intracellular bacteria is usually achieved by
      import of primary metabolites. Here, we report the identification of a candidate
      transporter protein from UWE25 that is highly specific for import of NAD+ when
      synthesized heterologously in Escherichia coli. The discovery of this candidate
      NAD+/ADP exchanger demonstrates that intact NAD+ molecules can be transported
      through cytoplasmic membranes. This protein acts together with a newly discovered
      nucleotide transporter and an ATP/ADP translocase, and allows UWE25 to exploit
      its host cell by means of a sophisticated metabolic parasitism.

PMID- 15577911
TI  - Haemangioblast commitment is initiated in the primitive streak of the mouse
      embryo.
AB  - Haematopoietic and vascular cells are thought to arise from a common progenitor
      called the haemangioblast. Support for this concept has been provided by
      embryonic stem (ES) cell differentiation studies that identified the blast colony
      forming cell (BL-CFC), a progenitor with both haematopoietic and vascular
      potential. Using conditions that support the growth of BL-CFCs, we identify
      comparable progenitors that can form blast cell colonies (displaying
      haematopoietic and vascular potential) in gastrulating mouse embryos. Cell mixing
      and limiting dilution analyses provide evidence that these colonies are clonal,
      indicating that they develop from a progenitor with haemangioblast potential.
      Embryo-derived haemangioblasts are first detected at the mid-streak stage of
      gastrulation and peak in number during the neural plate stage. Analysis of
      embryos carrying complementary DNA of the green fluorescent protein targeted to
      the brachyury locus demonstrates that the haemangioblast is a subpopulation of
      mesoderm that co-expresses brachyury (also known as T) and Flk-1 (also known as
      Kdr). Detailed mapping studies reveal that haemangioblasts are found at highest
      frequency in the posterior region of the primitive streak, indicating that
      initial stages of haematopoietic and vascular commitment occur before blood
      island development in the yolk sac.

PMID- 15577912
TI  - The role of barren stalk1 in the architecture of maize.
AB  - The architecture of higher plants is established through the activity of lateral
      meristems--small groups of stem cells formed during vegetative and reproductive
      development. Lateral meristems generate branches and inflorescence structures,
      which define the overall form of a plant, and are largely responsible for the
      evolution of different plant architectures. Here, we report the isolation of the
      barren stalk1 gene, which encodes a non-canonical basic helix-loop-helix protein
      required for the initiation of all aerial lateral meristems in maize. barren
      stalk1 represents one of the earliest genes involved in the patterning of maize
      inflorescences, and, together with the teosinte branched1 gene, it regulates
      vegetative lateral meristem development. The architecture of maize has been a
      major target of selection for early agriculturalists and modern farmers, because
      it influences harvesting, breeding strategies and mechanization. By sampling
      nucleotide diversity in the barren stalk1 region, we show that two haplotypes
      entered the maize gene pool from its wild progenitor, teosinte, and that only one
      was incorporated throughout modern inbreds, suggesting that barren stalk1 was
      selected for agronomic purposes.

PMID- 15577913
TI  - The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.
AB  - The human proto-oncogene BCL6 encodes a BTB/POZ-zinc-finger transcriptional
      repressor that is necessary for germinal-centre formation and is implicated in
      the pathogenesis of B-cell lymphoma. The precise function of BCL6 in germinal
      centre development and lymphomagenesis is unclear because very few direct BCL6
      target genes have been identified. Here we report that BCL6 suppresses the
      expression of the p53 (also known as tp53) tumour suppressor gene and modulates
      DNA damage-induced apoptotic responses in germinal-centre B cells. BCL6 represses
      p53 transcription by binding two specific DNA sites within the p53 promoter
      region and, accordingly, p53 expression is absent in germinal-centre B cells
      where BCL6 is highly expressed. Suppression of BCL6 expression via specific short
      interfering RNA leads to increased levels of p53 messenger RNA and protein both
      under basal conditions and in response to DNA damage. Most notably, constitutive
      expression of BCL6 protects B cell lines from apoptosis induced by DNA damage.
      These results suggest that an important function of BCL6 is to allow germinal
      centre B cells to tolerate the physiological DNA breaks required for
      immunoglobulin class switch recombination and somatic hypermutation without
      inducing a p53-dependent apoptotic response. These findings also imply that
      deregulated BCL6 expression contributes to lymphomagenesis in part by functional
      inactivation of p53.

PMID- 15577914
TI  - Regulation of cellular response to oncogenic and oxidative stress by Seladin-1.
AB  - Expression of multiple oncogenes and inactivation of tumour suppressors is
      required to transform primary mammalian cells into cancer cells. Activated Ha
      RasV12 (Ras) is usually associated with cancer, but it also produces paradoxical
      premature senescence in primary cells by inducing reactive oxygen species
      followed by accumulation of tumour suppressors p53 and p16(INK4a) (ref. 4). Here
      we identify, using a direct genetic screen, Seladin-1 (also known as Dhcr24) as a
      key mediator of Ras-induced senescence. Following oncogenic and oxidative stress,
      Seladin-1 binds p53 amino terminus and displaces E3 ubiquitin ligase Mdm2 from
      p53, thus resulting in p53 accumulation. Additionally, Seladin-1 associates with
      Mdm2 independently of p53, potentially affecting other Mdm2 targets. Ablation of
      Seladin-1 causes the bypass of Ras-induced senescence in rodent and human
      fibroblasts, and allows Ras to transform these cells. Wild-type Seladin-1, but
      not mutants that disrupt its association with either p53 or Mdm2, suppresses the
      transformed phenotype. The same mutants are also inactive in directing p53
      dependent oxidative stress response. These results show an unanticipated role for
      Seladin-1, previously implicated in Alzheimer's disease and cholesterol
      metabolism, in integrating cellular response to oncogenic and oxidative stress.

PMID- 15577915
TI  - Poly(ADP-ribose) is required for spindle assembly and structure.
AB  - The mitotic spindle is typically thought of as an array of microtubules,
      microtubule-associated proteins and motors that self-organizes to align and
      segregate chromosomes. The major spindle components consist of proteins and DNA,
      the primary structural elements of the spindle. Other macromolecules including
      RNA and lipids also associate with spindles, but their spindle function, if any,
      is unknown. Poly(ADP-ribose) (PAR) is a large, branched, negatively charged
      polymeric macromolecule whose polymerization onto acceptor proteins is catalysed
      by a family of poly(ADP-ribose) polymerases (PARPs). Several PARPs localize to
      the spindle in vertebrate cells, suggesting that PARPs and/or PAR have a role in
      spindle function. Here we show that PAR is enriched in the spindle and is
      required for spindle function--PAR hydrolysis or perturbation leads to rapid
      disruption of spindle structure, and hydrolysis during spindle assembly blocks
      the formation of bipolar spindles. PAR exhibits localization dynamics that differ
      from known spindle proteins and are consistent with a low rate of turnover in the
      spindle. Thus, PAR is a non-proteinaceous, non-chromosomal component of the
      spindle required for bipolar spindle assembly and function.

PMID- 15577918
TI  - A dose of reality.

PMID- 15577919
TI  - Experts, truth and scepticism.

PMID- 15577920
TI  - Perceptions about postdocs.

PMID- 15577921
TI  - Feeling 'better than well'.

PMID- 15577923
TI  - DNA or loving care?

PMID- 15577922
TI  - The environmental side effects of medication.

PMID- 15577924
TI  - Beyond an ERC.

PMID- 15577925
TI  - Should auld acquaintance be forgot...

PMID- 15577926
TI  - Always look on the bright site of Rho: structural implications for a conserved
      intermolecular interface.
AB  - The signalling functions of Rho-family GTPases are based on the formation of
      distinctive protein-protein complexes. Invaluable insights into the structure
      function relationships of the Rho GTPases have been obtained through the
      resolution of several of their structures in complex with regulators and
      downstream effectors. In this review, we use these complexes to compare the
      binding and specificity-determining sites of the Rho GTPases. Although the
      properties that characterize these sites are diverse, some fundamental conserved
      principles that govern their intermolecular interactions have emerged. Notably,
      all of the interacting partners of the Rho GTPases, irrespective of their
      function, bind to a common set of conserved amino acids that are clustered on the
      surface of the switch regions. This conserved region and its specific structural
      characteristics exemplify the convergence of the Rho GTPases on a consensus
      binding site.

PMID- 15577927
TI  - Regulation of eukaryotic translation by the RACK1 protein: a platform for
      signalling molecules on the ribosome.
AB  - The receptor for activated C-kinase (RACK1) is a scaffold protein that is able to
      interact simultaneously with several signalling molecules. It binds to protein
      kinases and membrane-bound receptors in a regulated fashion. Interestingly, RACK1
      is also a constituent of the eukaryotic ribosome, and a recent cryo-electron
      microscopy study localized it to the head region of the 40S subunit in the
      vicinity of the messenger RNA (mRNA) exit channel. RACK1 recruits activated
      protein kinase C to the ribosome, which leads to the stimulation of translation
      through the phosphorylation of initiation factor 6 and, potentially, of mRNA
      associated proteins. RACK1 therefore links signal-transduction pathways directly
      to the ribosome, which allows translation to be regulated in response to cell
      stimuli. In addition, the fact that RACK1 associates with membrane-bound
      receptors indicates that it promotes the docking of ribosomes at sites where
      local translation is required, such as focal adhesions.

PMID- 15577928
TI  - Survival of protozoan intracellular parasites in host cells.
AB  - The most common human diseases are caused by pathogens. Several of these
      microorganisms have developed efficient ways in which to exploit host molecules,
      along with molecular pathways to ensure their survival, differentiation and
      replication in host cells. Although the contribution of the host cell to the
      development of many intracellular pathogens (particularly viruses and bacteria)
      has been unequivocally established, the study of host-cell requirements during
      the life cycle of protozoan parasites is still in its infancy. In this review, we
      aim to provide some insight into the manipulation of the host cell by parasites
      through discussing the hurdles that are faced by the latter during infection.

PMID- 15577929
TI  - Exotic emerging viral diseases: progress and challenges.
AB  - The agents causing viral hemorrhagic fever (VHF) are a taxonomically diverse
      group of viruses that may share commonalities in the process whereby they produce
      systemic and frequently fatal disease. Significant progress has been made in
      understanding the biology of the Ebola virus, one of the best known examples.
      This knowledge has guided our thinking about other VHF agents, including Marburg,
      Lassa, the South American arenaviruses, yellow fever, Crimean-Congo and Rift
      Valley fever viruses. Comparisons among VHFs show that a common pathogenic
      feature is their ability to disable the host immune response by attacking and
      manipulating the cells that initiate the antiviral response. Of equal importance,
      these comparisons highlight critical gaps in our knowledge of these pathogens.

PMID- 15577930
TI  - Antibacterial resistance worldwide: causes, challenges and responses.
AB  - The optimism of the early period of antimicrobial discovery has been tempered by
      the emergence of bacterial strains with resistance to these therapeutics. Today,
      clinically important bacteria are characterized not only by single drug
      resistance but also by multiple antibiotic resistance--the legacy of past decades
      of antimicrobial use and misuse. Drug resistance presents an ever-increasing
      global public health threat that involves all major microbial pathogens and
      antimicrobial drugs.

PMID- 15577931
TI  - Advances in detecting and responding to threats from bioterrorism and emerging
      infectious disease.
AB  - Much progress has been made in recent years to strengthen local, state, national
      and international capacities to detect and respond to bioterrorism events and
      naturally occurring outbreaks of disease. New tools and systems are available to
      estimate the potential impact of a biological event and predict resource needs
      for effective response, enable earlier detection of an attack or outbreak,
      enhance diagnostic capacity and facilitate rapid intervention to mitigate the
      impact of an event on a community. These advances have required new approaches to
      preparedness, planning and surveillance, as well as new partnerships and
      collaborations across a range of disciplines. We examine some of these
      developments, discuss potential uses and limitations of these approaches, and
      identify priorities for the future.

PMID- 15577932
TI  - Research on infectious diseases requires better coordination.
AB  - This special supplement of Nature Medicine, directed at the topic of emerging
      infectious diseases, is very timely. Recent high-profile outbreaks have
      highlighted the global risk that infectious agents, both new and old, represent
      for society. The experience of severe acute respiratory syndrome (SARS) shows the
      risk posed by emerging infectious diseases, but also the power of strongly
      coordinated global surveillance and public health measures, coupled with
      scientific research, to keep infection under control. Diseases such as drug
      resistant malaria continue to be threats. There is a need to enhance global
      resources to investigate, detect and respond to emerging infections, and to
      appropriately coordinate and direct research efforts to meet the challenges
      presented by these diseases.

PMID- 15577933
TI  - Man versus microbe.

PMID- 15577934
TI  - Social and environmental risk factors in the emergence of infectious diseases.
AB  - Fifty years ago, the age-old scourge of infectious disease was receding in the
      developed world in response to improved public health measures, while the advent
      of antibiotics, better vaccines, insecticides and improved surveillance held the
      promise of eradicating residual problems. By the late twentieth century, however,
      an increase in the emergence and re-emergence of infectious diseases was evident
      in many parts of the world. This upturn looms as the fourth major transition in
      human-microbe relationships since the advent of agriculture around 10,000 years
      ago. About 30 new diseases have been identified, including Legionnaires' disease,
      human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS),
      hepatitis C, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob
      disease (vCJD), Nipah virus, several viral hemorrhagic fevers and, most recently,
      severe acute respiratory syndrome (SARS) and avian influenza. The emergence of
      these diseases, and resurgence of old ones like tuberculosis and cholera,
      reflects various changes in human ecology: rural-to-urban migration resulting in
      high-density peri-urban slums; increasing long-distance mobility and trade; the
      social disruption of war and conflict; changes in personal behavior; and,
      increasingly, human-induced global changes, including widespread forest clearance
      and climate change. Political ignorance, denial and obduracy (as with HIV/AIDS)
      further compound the risks. The use and misuse of medical technology also pose
      risks, such as drug-resistant microbes and contaminated equipment or biological
      medicines. A better understanding of the evolving social dynamics of emerging
      infectious diseases ought to help us to anticipate and hopefully ameliorate
      current and future risks.

PMID- 15577935
TI  - Molecular constraints to interspecies transmission of viral pathogens.
AB  - The successful replication of a viral pathogen in a host is a complex process
      involving many interactions. These interactions develop from the coevolution of
      pathogen and host and often lead to a species specificity of the virus that can
      make interspecies transmissions difficult. Nevertheless, viruses do sporadically
      cross species barriers into other host populations, including humans. In zoonotic
      infections, many of these interspecies transfer events are dead end, where
      transmission is confined only to the animal-to-human route but sometimes viruses
      adapt to enable spread from human to human. A pathogen must overcome many hurdles
      to replicate successfully in a foreign host. The viral pathogen must enter the
      host cell, replicate with the assistance of host factors, evade inhibitory host
      products, exit the first cell and move on to the next, and possibly leave the
      initial host and transmit to another. Each of these stages may require adaptive
      changes in the pathogen. Although the factors that influence each stage of the
      replication and transmission of most agents have not been resolved, the genomics
      of both hosts and pathogens are now at hand and we have begun to understand some
      of the molecular changes that enable some viruses to adapt to a new host.

PMID- 15577936
TI  - Influenza: old and new threats.
AB  - Influenza remains an important disease in humans and animals. In contrast to
      measles, smallpox and poliomyelitis, influenza is caused by viruses that undergo
      continuous antigenic change and that possess an animal reservoir. Thus, new
      epidemics and pandemics are likely to occur in the future, and eradication of the
      disease will be difficult to achieve. Although it is not clear whether a new
      pandemic is imminent, it would be prudent to take into account the lessons we
      have learned from studying different human and animal influenza viruses.
      Specifically, reconstruction of the genes of the 1918 pandemic virus and studies
      on their contribution to virulence will be important steps toward understanding
      the biological capabilities of this lethal virus. Increasing the availability of
      new antiviral drugs and developing superior vaccines will provide us with better
      approaches to control influenza and to have a positive impact on disease load. A
      concern is that the imposition of new rules for working with infectious influenza
      viruses under high security and high containment conditions will stifle
      scientific progress. The complex questions of what makes an influenza virus
      transmissible from one human to another and from one species to another, as well
      as how the immune system interacts with the virus, will require the active
      collaboration and unencumbered work of many scientific groups.

PMID- 15577937
TI  - Severe acute respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized
      animal coronavirus that exploited opportunities provided by 'wet markets' in
      southern China to adapt to become a virus readily transmissible between humans.
      Hospitals and international travel proved to be 'amplifiers' that permitted a
      local outbreak to achieve global dimensions. In this review we will discuss the
      substantial scientific progress that has been made towards understanding the
      virus-SARS coronavirus (SARS-CoV)-and the disease. We will also highlight the
      progress that has been made towards developing vaccines and therapies The
      concerted and coordinated response that contained SARS is a triumph for global
      public health and provides a new paradigm for the detection and control of future
      emerging infectious disease threats.

PMID- 15577938
TI  - Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West
      Nile and dengue viruses.
AB  - Mosquito-borne flaviviruses provide some of the most important examples of
      emerging and resurging diseases of global significance. Here, we describe three
      of them: the resurgence of dengue in tropical and subtropical areas of the world,
      and the spread and establishment of Japanese encephalitis and West Nile viruses
      in new habitats and environments. These three examples also illustrate the
      complexity of the various factors that contribute to their emergence, resurgence
      and spread. Whereas some of these factors are natural, such as bird migration,
      most are due to human activities, such as changes in land use, water impoundments
      and transportation, which result in changed epidemiological patterns. The three
      examples also show the ease with which mosquito-borne viruses can spread to and
      colonize new areas, and the need for continued international surveillance and
      improved public health infrastructure to meet future emerging disease threats.

PMID- 15577939
TI  - Molecular basis for TPR domain-mediated regulation of protein phosphatase 5.
AB  - Protein phosphatase 5 (Ppp5) is a serine/threonine protein phosphatase comprising
      a regulatory tetratricopeptide repeat (TPR) domain N-terminal to its phosphatase
      domain. Ppp5 functions in signalling pathways that control cellular responses to
      stress, glucocorticoids and DNA damage. Its phosphatase activity is suppressed by
      an autoinhibited conformation maintained by the TPR domain and a C-terminal
      subdomain. By interacting with the TPR domain, heat shock protein 90 (Hsp90) and
      fatty acids including arachidonic acid stimulate phosphatase activity. Here, we
      describe the structure of the autoinhibited state of Ppp5, revealing mechanisms
      of TPR-mediated phosphatase inhibition and Hsp90- and arachidonic acid-induced
      stimulation of phosphatase activity. The TPR domain engages with the catalytic
      channel of the phosphatase domain, restricting access to the catalytic site. This
      autoinhibited conformation of Ppp5 is stabilised by the C-terminal alphaJ helix
      that contacts a region of the Hsp90-binding groove on the TPR domain. Hsp90
      activates Ppp5 by disrupting TPR-phosphatase domain interactions, permitting
      substrate access to the constitutively active phosphatase domain, whereas
      arachidonic acid prompts an alternate conformation of the TPR domain,
      destabilising the TPR-phosphatase domain interface.

PMID- 15577940
TI  - A phospholipid sensor controls mechanogating of the K+ channel TREK-1.
AB  - TREK-1 (KCNK2 or K(2P)2.1) is a mechanosensitive K(2P) channel that is opened by
      membrane stretch as well as cell swelling. Here, we demonstrate that membrane
      phospholipids, including PIP(2), control channel gating and transform TREK-1 into
      a leak K(+) conductance. A carboxy-terminal positively charged cluster is the
      phospholipid-sensing domain that interacts with the plasma membrane. This region
      also encompasses the proton sensor E306 that is required for activation of TREK-1
      by cytosolic acidosis. Protonation of E306 drastically tightens channel
      phospholipid interaction and leads to TREK-1 opening at atmospheric pressure. The
      TREK-1-phospholipid interaction is critical for channel mechano-, pH(i)- and
      voltage-dependent gating.

PMID- 15577941
TI  - In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to
      chemical repellents.
AB  - ASH sensory neurons are required in Caenorhabditis elegans for a wide range of
      avoidance behaviors in response to chemical repellents, high osmotic solutions
      and nose touch. The ASH neurons are therefore hypothesized to be polymodal
      nociceptive neurons. To understand the nature of polymodal sensory response and
      adaptation at the cellular level, we expressed the calcium indicator protein
      cameleon in ASH and analyzed intracellular Ca(2+) responses following stimulation
      with chemical repellents, osmotic shock and nose touch. We found that a variety
      of noxious stimuli evoked strong responses in ASH including quinine, denatonium,
      detergents, heavy metals, both hyper- and hypo-osmotic shock and nose touch. We
      observed that repeated chemical stimulation led to a reversible reduction in the
      magnitude of the sensory response, indicating that adaptation occurs within the
      ASH sensory neuron. A key component of ASH adaptation is GPC-1, a G-protein gamma
      subunit expressed specifically in chemosensory neurons. We hypothesize that G
      protein gamma-subunit heterogeneity provides a mechanism for repellent-specific
      adaptation, which could facilitate discrimination of a variety of repellents by
      these polymodal sensory neurons.

PMID- 15577942
TI  - The chromatin remodeling complex NoRC controls replication timing of rRNA genes.
AB  - The ATP-dependent chromatin remodeling complex NoRC silences a fraction of
      mammalian ribosomal RNA genes (rDNA) by establishing heterochromatic structures
      at the rDNA promoter. Here we show that NoRC also plays a role in replication
      timing of rDNA. rDNA is replicated in a biphasic manner, active genes (
      approximately 60%) replicating early and silent ones ( approximately 40%)
      replicating late in S-phase. The chromatin structure that marks active and silent
      rDNA repeats is propagated during cell division. To examine the function of NoRC
      in epigenetic inheritance and replication timing, we have monitored the chromatin
      structure, transcriptional activity and replication timing of rDNA in a cell line
      that moderately overexpresses NoRC. NoRC is exclusively associated with late
      replicating rDNA arrays. Overexpression of NoRC silences rDNA transcription,
      reduces the size and number of nucleoli, impairs cell proliferation and resets
      replication timing from early to late. The results demonstrate that NoRC is an
      important determinant of replication timing and epigenetic marks are heritably
      maintained through DNA replication.

PMID- 15577943
TI  - Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal
      transduction pathway.
AB  - Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated
      protein kinase (MAPK), which is regulated by protein stability. However, its
      function is unknown and no physiological substrates for ERK3 have yet been
      identified. Here we demonstrate a specific interaction between ERK3 and MAPK
      activated protein kinase-5 (MK5). Binding results in nuclear exclusion of both
      ERK3 and MK5 and is accompanied by ERK3-dependent phosphorylation and activation
      of MK5 in vitro and in vivo. Endogenous MK5 activity is significantly reduced by
      siRNA-mediated knockdown of ERK3 and also in fibroblasts derived from ERK3-/-
      mice. Furthermore, increased levels of ERK3 protein detected during nerve growth
      factor-induced differentiation of PC12 cells are accompanied by an increase in
      MK5 activity. Conversely, MK5 depletion causes a dramatic reduction in endogenous
      ERK3 levels. Our data identify the first physiological protein substrate for ERK3
      and suggest a functional link between these kinases in which MK5 is a downstream
      target of ERK3, while MK5 acts as a chaperone for ERK3. Our findings provide
      valuable tools to further dissect the regulation and biological roles of both
      ERK3 and MK5.

PMID- 15577944
TI  - Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation.
AB  - Retinoblastoma gene product (pRB) plays critical roles in regulation of the cell
      cycle and tumor suppression. It is known that downregulation of pRB can stimulate
      carcinogenesis via abrogation of the pRB pathway, although the mechanism has not
      been elucidated. In this study, we found that Mdm2, a ubiquitin ligase for p53,
      promoted ubiquitin-dependent degradation of pRB. pRB was efficiently
      ubiquitinated by wild-type Mdm2 in vivo as well as in vitro, but other RB family
      proteins were not. Mutant Mdm2 with a substitution in the RING finger domain
      showed dominant-negative stabilization of pRB. Both knockout and knockdown of
      Mdm2 caused accumulation of pRB. Moreover, Mdm2 inhibited pRB-mediated flat
      formation of Saos-2 cells. Downregulation of pRB expression was correlated with a
      high level of expression of Mdm2 in human lung cancers. These results suggest
      that Mdm2 regulates function of pRB via ubiquitin-dependent degradation of pRB.

PMID- 15578005
TI  - Effects of l-stepholidine on forebrain Fos expression: comparison with clozapine
      and haloperidol.
AB  - l-Stepholidine (SPD) is a tetrahydroprotoberberine alkaloid and a mixed dopamine
      D1 agonist/D2 antagonist. Preliminary clinical trials suggest that SPD improves
      both positive and negative symptoms of schizophrenia without producing
      significant extrapyramidal side effects. Here, we report that SPD mimics the
      effect of the atypical antipsychotic drug clozapine, preferentially increasing
      Fos expression in corticolimbic areas. Thus, at 10 mg/kg (i.p.), SPD induced Fos
      expression in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and
      lateral septal nucleus (LSN) without significantly affecting the dorsolateral
      striatum (DLSt). At higher doses (20-40 mg/kg), SPD also increased Fos expression
      in the DLSt. The increase, however, was less pronounced than the increase seen in
      the NAc. Within the NAc, SPD also induced more Fos expression in the shell than
      in the core. In all subcortical areas examined, the Fos expression induced by SPD
      was mimicked by the D2 antagonist sulpiride and reversed by the D2 agonist
      quinpirole, suggesting that the effect is due to blockade of D2-like receptors by
      SPD. In the mPFC, however, the effect was not mimicked by sulpride or reversed by
      quinpirole. It was also not mimicked by the D1 agonist SKF38393 or SKF38393 plus
      sulpride, and not reversed by the D1 antagonist SCH23390. These results suggest
      that, in the mPFC, SPD may induce Fos expression through a non-DA mechanism.
      Whether the mechanism involves an interaction of SPD with other neurotransmitters
      such as 5-HT and norepinephrine remains to be determined.

PMID- 15578006
TI  - Cognitive improvement in schizophrenic patients does not require a serotonergic
      mechanism: randomized controlled trial of olanzapine vs amisulpride.
AB  - Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been
      proposed as a candidate mechanism by which second-generation antipsychotics
      (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in
      contrast to antipsychotics of the first generation. The SGA amisulpride, however,
      only binds to D2/D3 receptors, which makes it an interesting tool to test this
      assumption. In a randomized controlled trial, 52 schizophrenic patients were
      allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400
      800 mg/day). A comprehensive neuropsychological test battery and clinical ratings
      were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive
      improvements of moderate size were observed, with effect sizes similar to those
      obtained in previous studies on the cognitive effects of SGAs. Importantly,
      amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5
      HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement
      by SGAs.

PMID- 15578007
TI  - Cognitive deficits caused by late gestational disruption of neurogenesis in rats:
      a preclinical model of schizophrenia.
AB  - Late gestational disruption of neurogenesis in rats has been shown to induce
      behavioral abnormalities thought to mimic aspects of positive and negative
      symptoms of schizophrenia. Furthermore, it has been shown that the morphological
      changes produced by the perturbation are relevant to schizophrenia with reduced
      thickness of the hippocampus, thalamus, and cortical regions. In addition to the
      positive and negative symptoms, schizophrenia is associated with deficits in a
      wide variety of cognitive domains. In the present studies, we assessed whether
      the cognitive deficits are modeled by disruption of neurogenesis late during
      gestation (gestational day 17) in the rat. In the battery of tests utilized, we
      describe that rats in which neurogenesis was disrupted have deficits in a
      reversal-learning paradigm of the Morris water maze and in object recognition,
      and that they exhibit perseveration in the Porsolt forced swimming test.
      Additionally, we found deficient associative learning in an acquisition of an
      active avoidance paradigm and deficits in latent inhibition. No deficits were
      observed in the reference memory version of the Morris water maze and in a non
      match-to position experiment, showing that the deficits are limited to certain
      aspects of cognition.

PMID- 15578008
TI  - Self-reported depressive symptom measures: sensitivity to detecting change in a
      randomized, controlled trial of chronically depressed, nonpsychotic outpatients.
AB  - This study evaluated and compared the performance of three self-report measures:
      (1) 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR30); (2) 16
      item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16); and
      (3) Patient Global Impression-Improvement (PGI-I) in assessing clinical outcomes
      in depressed patients during a 12-week, acute phase, randomized, controlled trial
      comparing nefazodone, cognitive-behavioral analysis system of psychotherapy
      (CBASP), and the combination in the treatment of chronic depression. The IDS
      SR30, QIDS-SR16, PGI-I, and the 24-item Hamilton Depression Rating Scale (HDRS24)
      ratings were collected at baseline and at weeks 1-4, 6, 8, 10, and 12. Response
      was defined a priori as a > or =50% reduction in baseline total score for the IDS
      SR30 or for the QIDS-SR16 or as a PGI-I score of 1 or 2 at exit. Overall response
      rates (LOCF) to nefazodone were 41% (IDS-SR30), 45% (QIDS-SR16), 53% (PCI-I), and
      47% (HDRS17). For CBASP, response rates were 41% (IDS-SR30), 45% (QIDS-SR16), 48%
      (PGI-I), and 46% (HDRS17). For the combination, response rates were 68% (IDS-SR30
      and QIDS-SR16), 73% (PGI-I), and 76% (HDRS17). Similarly, remission rates were
      comparable for nefazodone (IDS-SR30=32%, QIDS-SR16=28%, PGI-I=22%, HDRS17=30%),
      for CBASP (IDS-SR30=32%, QIDS-SR16=30%, PGI-I=21%, HDRS17=32%), and for the
      combination (IDS-SR30=52%, QIDS-SR16=50%, PGI-I=25%, HDRS17=49%). Both the IDS
      SR30 and QIDS-SR16 closely mirrored and confirmed findings based on the HDRS24.
      These findings raise the possibility that these two self-reports could provide
      cost- and time-efficient substitutes for clinician ratings in treatment trials of
      outpatients with nonpsychotic MDD without cognitive impairment. Global patient
      ratings such as the PGI-I, as opposed to specific item-based ratings, provide
      less valid findings.

PMID- 15578009
TI  - Comparison of the reinforcing effects of cocaine and cocaine/heroin combinations
      under progressive ratio and choice schedules in rats.
AB  - The co-use of cocaine and heroin is relatively common, with a growing clinical
      and preclinical literature dedicated to investigating the factors underlying the
      phenomenon. Specifically, several studies have compared the reinforcing effects
      of the coadministration of cocaine and heroin, referred to commonly as
      'speedball', to either drug alone. The present study assessed whether addition of
      heroin to a wide range of cocaine doses produces reinforcing effects greater than
      cocaine alone using both a progressive ratio (PR) schedule and a choice
      procedure. Patterns of coadministration of cocaine and heroin offered
      simultaneously were also assessed using double-lumen cannulas. Under the PR
      schedule, speedball combinations across a range of doses (0.38-3.0 mg/kg/inf
      cocaine+1.5-48 microg/kg/inf heroin) did not support higher break points than
      cocaine alone. When cocaine and heroin were made available concurrently (ie on
      two separate levers), rats self-administered cocaine exclusively. Using a choice
      procedure, however, a preference was demonstrated for some speedball combinations
      (eg 0.18 mg/kg/inf cocaine+50 microg/kg/inf heroin; 0.38 mg/kg/inf cocaine+50
      microg/kg/inf heroin) over cocaine alone (0.75 mg/kg/inf). So while results
      obtained using the PR schedule do not support the hypothesis that speedball
      combinations are more reinforcing than cocaine alone, data from the choice
      procedure do support this hypothesis. These apparently discrepant results
      demonstrate that these models are measuring different aspects of drug
      reinforcement, and suggest that choice procedures in rats provide a useful tool
      to study speedball self-administration.

PMID- 15578029
TI  - Platelet transfusions in infants with necrotizing enterocolitis do not lower
      mortality but may increase morbidity.
AB  - OBJECTIVE: Necrotizing enterocolitis (NEC), a serious multisystemic inflammatory
      disease most commonly seen in premature neonates, is often associated with
      thrombocytopenia. Infants with severe forms of NEC commonly have platelet counts
      of less than 50,000/mm(3), occasionally less than 10,000/mm(3). Despite an
      absence of data to support the practice, platelet transfusions are commonly used
      to maintain a certain arbitrary platelet count in an effort to prevent bleeding.
      As platelet transfusions contain a variety of bioactive factors including pro
      inflammatory cytokines, we hypothesized that a higher number and volume of
      platelet transfusions would not be associated with an improvement in mortality or
      morbidity. STUDY DESIGN: A retrospective cohort analysis was conducted of the
      medical records of all infants between 1997 and 2001 with Bell's Stage 2 or 3 NEC
      associated with platelet counts of <100,000/mm(3). The medical records were
      evaluated for the following variables: platelet counts, number and volume of
      platelet transfusions, symptoms of bleeding, and hospital course. Mortality and
      development of short bowel syndrome and/or cholestasis were correlated to the
      total number and volume (total ml and ml/kg) of platelet transfusions.
      Differences between the outcome groups were compared using the independent t
      test, Fisher's exact test and Mann-Whitney tests. RESULTS: A total of 46 infants
      met the study criteria (gestational age 28+/-4 weeks and birth weight 1166+/-756
      g, mean+/-SD). There were a total of 406 platelet transfusions administered to
      the study population. Of these, 151 (37.2%) were given in the presence of active
      bleeding, with 62% of these resulting in the cessation of bleeding within 24
      hours. Other listed indications for platelet transfusions were hypovolemia and
      severe thrombocytopenia. On analysis of the entire cohort, there was no
      statistical improvement in either mortality or morbidity (short bowel syndrome
      and cholestasis) with greater number and/or volume of platelet transfusions.
      Furthermore, we found that infants who developed short bowel syndrome and/or
      cholestasis had been given a significantly higher number and volume of platelet
      transfusions when compared to those who did not have these adverse outcomes
      [median (minimum - maximum) - number of transfusions : 9 (0 to 33) vs 1.5 (0 to
      20), p=0.010; volume of transfusions (ml/kg): 121.5 (0 to 476.6) vs 33.2 (0 to
      224.3), p=0.013]. CONCLUSION: This retrospective analysis suggests that greater
      number and volume of platelet transfusions in infants with necrotizing
      enterocolitis are associated with greater morbidity in the form of short bowel
      syndrome and/or cholestasis without the benefit of lower mortality.

PMID- 15578030
TI  - Mean arterial pressure in concordant and discordant triplets during the first
      week of life.
AB  - OBJECTIVE: To retrospectively determine mean arterial pressure (MAP) for stable
      concordant and discordant triplets during the first 7 days of life. BACKGROUND:
      Morbidity and mortality for prematurely born triplets is high, therefore, MAP
      monitoring during the first day of life is important for their clinical
      management. MAP reference values for special populations such as triplets have
      not been published. Recently, we reported that in stable discordant twins MAP
      values during the first day of life were significantly lower in the smaller than
      in their larger siblings. Comparable information for triplets is not available.
      DESIGN: Retrospective cohort study. METHODS: We studied 30 sets of concordant and
      29 sets of discordant (birth weight difference > or =20%) consecutively born
      triplets. Stable patients were defined as those having umbilical cord hemoglobin
      > or =13 g/dl, normal blood gases, who were never treated for hypotension, and
      survived at least 7 days. MAP (torr) were measured by oscillometry in 3410, and
      by transducer via an umbilical arterial catheter in 1251 instances. RESULTS:
      Concordant and discordant triplets were similar in demographics, history of
      preterm labor (63 and 63%), chorioamnionitis (10 and 10%), pre-eclampsia (53 and
      48%), cesarean delivery (100 and 100%), antenatal steroids (77 and 73%), cord
      hemoglobin (16 and 16 g/dl), combined triplets birth weight (4922 and 4732 g),
      gestational age (32 and 33 weeks), normal head ultrasounds or Grade I
      intracranial hemorrhage (96 and 100%) and neonatal mortality (2 and 1%), but were
      different in the number of infants requiring mechanical ventilation (57 and 31%).
      A total of 80 (89%) concordant triplets and 77 (88%) discordant triplets were
      stable according to our definition. Concordant stable triplets, whether small,
      medium or large, had similar MAP at birth. Their MAP values increased noticeably
      from birth to 24 hours and more subtlely to 7 days. Triplets of < or =32 weeks GA
      had lower MAP throughout than those of > or =33 weeks GA. Discordant stable
      triplets were divided into 27 small (1382 g), 26 medium (1683 g) and 27 large
      (1969 g); during the first 24 hours, medium and smaller triplets had MAP values
      that were lower than those of their larger siblings. From the second to the
      seventh day of life, all MAP values and trends were similar. Among discordant
      triplets, 86% of the smallest, 13% of the medium and 13% of the largest infants
      had asymmetrical intrauterine growth restriction. CONCLUSION: In stable
      concordant and stable discordant triplets, MAP correlates with birth weight,
      gestational age and postnatal age. MAP values increase noticeably during the
      first 24 hours and more subtlely during the next 7 days. Concordant or
      discordant, small, medium, and large triplets have similar MAP values and trends
      to that of their siblings. Small and medium discordant triplets have lower MAP
      values during the first day of life than their larger siblings but by the second
      day there MAP trends and values were no longer different.

PMID- 15578031
TI  - Patterns of thrombocytosis and thrombocytopenia in hospitalized neonates.
AB  - OBJECTIVE: We sought to identify changes in platelet (PLT) counts over time, and
      to evaluate the patterns of thrombocytopenia and thrombocytosis in hospitalized
      infants 23.8 weeks to term gestation. STUDY DESIGN: Neonates were divided into
      four gestational age groups and their PLT counts were retrospectively compared
      for prevalence of thrombocytopenia, thrombocytosis, and associated conditions.
      RESULTS: Postconceptional age, postnatal age, and sepsis (among other factors)
      affected PLT counts. When counts from noninfected appropriately grown infants
      were evaluated, the risk of thrombocytopenia and thrombocytosis were highest in
      the most preterm infants, and these risks changed with corrected gestational age.
      PLT counts increased weekly over the first 4 weeks of life for all but the most
      preterm infants. CONCLUSIONS: These data characterize the incidence of
      thrombocytopenia and thrombocytosis across a wide range of gestational ages and
      show that, even in noninfected neonates, these conditions are common, and risk
      decreases with increasing maturity. The age-related changes in PLT patterns may
      reflect maturation of platelet regulation.

PMID- 15578032
TI  - Risk factors for adverse neurodevelopment in extremely low birth weight infants
      with normal neonatal cranial ultrasound.
AB  - OBJECTIVES: To determine risk factors associated with adverse developmental
      outcome at 5 years in extremely low birth weight infants or extremely premature
      infants (<28 weeks) with normal neonatal cranial ultrasounds. DESIGN/METHODS:
      Data were collected prospectively on 152 infants with gestation <28 weeks or
      birth-weight <1000 g. Infants were grouped into those with normal development,
      mild-to-moderate impairment (IQ 70 to 84, or hearing loss 30 to 89 dB, visual
      acuity 6/18 to 6/60, or mild/moderate cerebral palsy (CP)) and severe impairment
      (IQ <70, hearing loss > or =90 dB, visual acuity <6/60, or severe CP). RESULTS:
      Five-year outcomes were available for 144/152 children (95%). In all, 89 (62%)
      infants had normal development, 39 (27%) had mild-moderate impairment and 16
      (11%) had severe impairment. On multivariate logistic regression analysis,
      factors associated with developmental impairment were serum bilirubin > or =200
      micromol/l (odds ratio (OR) - 4.06, p=0.003) and retinopathy of prematurity (ROP)
      (OR - 1.6, p=0.03). CONCLUSIONS: A serum bilirubin > or =200 micromol/l and
      presence of ROP are postnatal risk factors associated with an adverse
      developmental outcome in infants with normal cranial ultrasounds.

PMID- 15578034
TI  - Definition of the clinical spectrum of kernicterus and bilirubin-induced
      neurologic dysfunction (BIND).
AB  - Kernicterus, currently used to describe both the neuropathology of bilirubin
      induced brain injury and its associated clinical findings, is a complex syndrome.
      The neurobiology of kernicterus, including the determinants and mechanisms of
      neuronal injury, is discussed along with traditional and evolving definitions
      ranging from classical kernicterus with athetoid cerebral palsy, impaired upward
      gaze and deafness, to isolated conditions, for example, auditory neuropathy or
      dys-synchrony (AN/AD), and subtle bilirubin-induced neurological dysfunction
      (BIND). The clinical expression of BIND varies with location, severity, and time
      of assessment, influenced by the amount, duration and developmental age of
      exposure to excessive free bilirubin. Although total serum bilirubin (TSB) is
      important, kernicterus cannot be defined based solely on TSB. For study purposes
      kernicterus may be defined in term and near-term infants with TSB > or = 20 mg/dl
      using abnormal muscle tone on examination, auditory testing diagnostic of AN/AD,
      and magnetic resonance imaging showing bilateral lesions of globus pallidus+/
      subthalamic nucleus.

PMID- 15578033
TI  - Evaluation of eosinophilia in hospitalized preterm infants.
AB  - OBJECTIVE: To characterize changes in eosinophil counts over time, and to draw
      comparisons across four gestational age groups with respect to the incidence of,
      and clinical conditions associated with eosinophilia over the first months of
      life in a single neonatal intensive care unit (NICU). STUDY DESIGN: Weekly
      complete blood counts (CBCs) were collected from all NICU patients. Eosinophilia
      was classified as mild, moderate, or severe. Changes in eosinophil counts were
      examined over time, the incidence of eosinophilia was determined by gestational
      age group, and clinical correlations sought. RESULTS: Eosinophil data from 1652
      CBCs were analyzed from 332 infants. Eosinophilia occurred in 148 infants (45%)
      during their hospitalization. The prevalence, severity, and timing of
      eosinophilia varied by gestational age, infection, and red blood cell
      transfusions. CONCLUSIONS: The incidence and severity of eosinophilia increased
      with immaturity, and was temporally associated with infection, necrotizing
      enterocolitis, and packed red blood cell transfusion.

PMID- 15578035
TI  - High intakes of milk, but not meat, increase s-insulin and insulin resistance in
      8-year-old boys.
AB  - OBJECTIVE: Our objective was to examine if a high animal protein intake from milk
      or meat increased s-insulin and insulin resistance in healthy, prepubertal
      children. A high animal protein intake results in higher serum branched chain
      amino acids (BCAA; leucine, isoleucine and valine) concentrations, which are
      suggested to stimulate insulin secretion. Furthermore, milk possesses some
      postprandial insulinotrophic effect that is not related to its carbohydrate
      content. DESIGN: A total of 24 8-y-old boys were asked to take 53 g protein as
      milk or meat daily. At baseline and after 7 days, diet was registered, and
      insulin, glucose, and amino acids were determined. Insulin resistance and beta
      cell function were calculated with the homeostasis model assessment. RESULTS:
      Protein intake increased by 61 and 54% in the milk- and meat-group, respectively.
      In the milk-group, fasting s-insulin concentrations doubled, which caused the
      insulin resistance to increase similarly. In the meat-group, there was no
      increase in insulin and insulin resistance. As the BCAAs increased similarly in
      both groups, stimulation of insulin secretion through BCAAs is not supported.
      CONCLUSIONS: Our results indicate that a short-term high milk, but not meat,
      intake increased insulin secretion and resistance. The long-term consequences of
      this are unknown. The effect of high protein intakes from different sources on
      glucose-insulin metabolism needs further studying.

PMID- 15578036
TI  - Milky-white pleural effusion complicating peripherically inserted central venous
      catheter for total parenteral nutrition.
AB  - Pleural effusion secondary to vascular perforation and leakage of total
      parenteral nutrition (TPN) is a rare complication of central lines. We report
      such a case and urge physicians to familiarize with recognition and management of
      this rare complication as both TPN and central catheter lines are widely used
      techniques.

PMID- 15578038
TI  - Mosaic imprinting defect in a patient with an almost typical expression of the
      Prader-Willi syndrome.
AB  - We describe a young woman with Prader-Willi syndrome (PWS) due to a mosaic
      imprinting defect. Three independent assays revealed a reduced proportion of
      nonmethylated SNURF-SNRPN alleles in peripheral blood DNA: methylation-specific
      PCR followed by denaturing high-performance liquid chromatography (MSP/DHPLC),
      methylation-sensitive restriction enzyme analysis and methylation-specific real
      time PCR analysis. Microsatellite analysis and fluorescence in situ hybridisation
      revealed apparently normal chromosomes 15 of biparental origin. Based on the
      MSP/DHPLC and real-time PCR results, we estimate that approximately 50% of the
      patient's blood cells have an imprinting defect and 50% of the cells are normal.
      Apart from a rather normal facial appearance, the proband has typical features of
      PWS.

PMID- 15578039
TI  - The effect of PDE5 inhibition on the erectile function in streptozotocin-induced
      diabetic rats.
AB  - The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor,
      DA-8159, on erectile function throughout the quantitative analysis of vascular
      endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus
      cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA
      8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats.
      After 8 weeks, immunohistochemistry and computerized image analysis were
      performed to quantify the percent area within the Corpora Cavernosa occupied by
      the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure
      (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic
      rats showed a significant decrease in the SM and endothelial cell content, and an
      increase in the TGF-beta1 expression level within the cavernosa areas compared to
      the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1
      expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159
      prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and
      endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)).
      Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly
      lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)).
      Electrostimulation of the cavernous nerve induced significant increase in maximum
      ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area
      under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/
      2272 in diabetic group). These results suggest that subchronic treatment of DA
      8159 can prevent the development of erectile dysfunction (ED), and provides a
      rationale for the use of DA-8159 as treatment of diabetic ED.

PMID- 15578040
TI  - Increased estradiol levels in venous occlusive disorder: a possible functional
      mechanism of venous leakage.
AB  - Venous insufficiency of the corpora cavernosa is the second most common cause of
      erectile dysfunction (ED). A functional insufficiency of the venous system has
      been hypothesised, but the cause is still unclear. To evaluate a possible
      endocrine mechanism, we have studied hormone profile in a group of nine patients
      with pure venous-leakage (VL) compared with a control group of 15 patients with
      ED of different origin. Prolactin, testosterone and gonadotropin levels did not
      differ among the two groups, while estradiol (E2) plasma concentration was
      significantly higher in VL patients compared to controls. Our data support the
      hypothesis that the steroid environment, in particular estradiol level, can
      influence venous vascular tone (via VEGF or NO), thus affecting venous leakage
      dysfunction. This point can explain a possible link between the high estradiol
      levels and a functional insufficiency of the venous system in ED.

PMID- 15578042
TI  - Stable, long-term label opens doors for gene therapy.

PMID- 15578041
TI  - A complement receptor-1 polymorphism with high frequency in malaria endemic
      regions of Asia but not Africa.
AB  - Complement receptor-1 (CR1) is a ligand for rosette formation, a phenomenon
      associated with cerebral malaria (CM). Binding is dependent on erythrocyte CR1
      copy number. In Caucasians, low CR1 expressors have two linked mutations. We
      determined the Q981H and HindIII RFLP distribution in differing population groups
      to ascertain a possible role in adaptive evolution. We examined 194 Caucasians,
      180 Choctaw Indians, 93 Chinese-Taiwanese, 304 Cambodians, 89 Papua New Guineans
      (PNG) and 366 Africans. PCR/RFLP used HindIII for CR1 expression and BstNI for
      the Q981H mutation. DNA sequencing and pyrosequencing were performed to resolve
      inconclusive results. Gene frequencies for the L allele were 0.15 in Africans,
      0.16 in Choctaws, 0.18 in Caucasians, 0.29 in Chinese-Taiwanese, 0.47 in
      Cambodians and 0.58 in PNG. Allelic frequency for 981H were 0.07 in Africans,
      0.15 in Caucasians, 0.18 in Choctaws, 0.29 in Chinese-Taiwanese, 0.47 in
      Cambodians and 0.54 in PNG. The Q981H polymorphism correlates with the HindIII
      RFLP in most groups except West Africans and appears to be part of a low CR1
      expression haplotype. The gene frequency for the haplotype is highest in the
      malaria-endemic areas of Asia, suggesting that this haplotype may have evolved
      because it protects from rosetting and CM.

PMID- 15578043
TI  - Gene-mediated restoration of cartilage matrix by combination insulin-like growth
      factor-I/interleukin-1 receptor antagonist therapy.
AB  - Combination of growth factor gene-enhanced cartilage matrix synthesis with
      interleukin-1 receptor antagonist protein (IL-1Ra) abrogation of cartilage matrix
      degradation may reduce and possibly reverse cartilage loss in synovitis and
      osteoarthritis. The feasibility of cotransduction of synovial membrane with two
      such genes that may act on cartilage homeostasis was investigated in an in vitro
      coculture system. Cultured synoviocytes in monolayer were cotransduced with E1
      deleted adenoviral vectors, one containing IGF-I coding sequence under
      cytomegalovirus (CMV) promoter control (200 multiplicities of infection (moi)),
      and the second containing IL-1Ra sequence under CMV promoter control (100 moi).
      Adenovirus-IGF-I (AdIGF-I) transduction and AdIGF-I/AdIL-1Ra cotransduction of
      synovial monolayer cultures resulted in increased IGF-I mRNA and ligand
      expression, and similarly AdIL-1Ra and AdIGF-I/AdIL-1Ra-transduced cultures
      expressed high levels of IL-1Ra. Northern analysis confirmed a single mRNA
      transcript of the appropriate size for both IGF-I and IL-1Ra transgene
      expression. Synovial cell monolayer and cartilage explant coculture experiments
      were used to examine the effects of IGF-I and IL-1Ra protein expressed by
      transduced synoviocytes on normal and IL-1-depleted cartilage. Transduced
      monolayer cultures produced peak medium IGF-I content of 114+/-20.2 ng/ml and IL
      1Ra levels of 241.8+/-10.5 ng/ml at 48 h after transduction. These IGF-I
      concentrations were sufficient to produce significantly increased proteoglycan
      (PG) content of normal cartilage cultured in medium conditioned by AdIGF-I and
      AdIGF-I/AdIL-1Ra-transduced synoviocytes. Interleukin-1-exposed cartilage was
      markedly depleted of PG, and this catabolic state was partially reversed in AdIGF
      I-transduced cultures and fully reversed by AdIGF-I/AdIL-1Ra-transduced synovial
      cocultures. These data indicate that cultured synoviocytes are readily
      cotransduced by two recombinant adenoviral vectors containing transgenes active
      in restoring joint health. The AdIL-1Ra and AdIGF-I transgenes were abundantly
      expressed and the secreted products achieved therapeutic concentrations by day 2.
      The resulting increase in matrix biosynthesis returned cartilage PG content to
      normal levels. These data suggest that there may be significant value in
      cotransduction of synovial membrane to attenuate cartilage malacia associated
      with synovitis, injury, or early arthritis.

PMID- 15578044
TI  - Adenoviral overexpression of interleukin-1 receptor antagonist protein increases
      beta-cell replication in rat pancreatic islets.
AB  - The naturally occurring inhibitor of interleukin-1 (IL-1) action, interleukin-1
      receptor antagonist protein (IRAP), binds to the type 1 IL-1 receptor but does
      not initiate IL-1 signal transduction. In this study, we have determined the
      effects of IL-1beta and IRAP overexpression on adult beta-cell replication and
      viability. IL-1beta reduced dramatically beta-cell replication in adult rat
      islets both at 5.5 mM (control: 0.29+/-0.04%; IL-1beta: 0.02+/-0.02%, P<0.05) and
      22.2 mM glucose (control: 0.84+/-0.2%; IL-1beta: 0.05+/-0.05%, P<0.05). This
      effect was completely prevented in islets overexpressing IRAP after adenoviral
      gene transfer at 5.5 mM (Ad-IL-1Ra+IL-1beta: 0.84+/-0.1%, P<0.05) and 22.2 mM
      glucose (Ad-IL-1Ra+IL-1beta: 1.22+/-0.2%, P<0.05). Moreover, overexpression of
      IRAP increased glucose-stimulated beta-cell replication in the absence of IL
      1beta exposure (Ad-IL-1Ra: 1.59+/-0.5%, P<0.05). beta-Cell death (TUNEL
      technique) was increased in IL-1beta-exposed islets but not in Ad-IL-1Ra-infected
      islets (control: 0.82+/-0.2%; control+IL-1beta: 1.77+/-0.2; IRAP: 0.61+/-0.2%;
      IRAP+IL-1beta: 0.86+/-0.1%, P<0.05). Comparable results were obtained by flow
      cytometry. To determine the effect of IRAP overexpression on beta-cell
      replication in vivo, Ad-IL-1Ra-transduced islets were transplanted into
      streptozotocin diabetic rats. beta-Cell replication was significantly increased
      in IRAP-overexpressing islet grafts (0.98+/-0.3%, P<0.05) compared to normal
      pancreas (0.35+/-0.02%), but not in control islet grafts (0.50+/-0.1%). This
      study shows that in addition to the effects of IL-1beta on beta-cell viability,
      this cytokine exerts a deleterious action on beta-cell replication, which can be
      prevented by IRAP overexpression, and provides support for the potential use of
      IRAP as a therapeutic tool.

PMID- 15578045
TI  - Hox, ParaHox, ProtoHox: facts and guesses.
AB  - The Hox gene cluster has captivated the imagination of evolutionary and
      developmental biologists worldwide. In this review, the origin of the Hox and
      ParaHox gene clusters by duplication of a ProtoHox gene cluster, and the changes
      in their gene numbers in major Metazoan Transitions are reviewed critically. Re
      evaluation of existing data and recent findings in Cnidarians, Acoels, and
      critical stages of vertebrate evolution suggest alternative scenarios for the
      origin, structure, and changes in Hox gene numbers in relevant events of Metazoan
      evolution. I discuss opposing views and propose that (i) the ProtoHox cluster had
      only two genes, and not four as commonly believed: a corollary is that the origin
      of Bilaterians was coincident with the invention of new Hox and ParaHox gene
      classes, which may have facilitated such a transition; (ii) the ProtoHox cluster
      duplication was a cis duplication event, rather than a trans duplication event,
      as previously suggested, and (iii) the ancestral vertebrate cluster possessed 14
      Hox genes, and not the 13 generally assumed. These hypotheses could be verified
      or refuted in the near future, but they may help critical discussion of the
      evolution of the Hox/ParaHox family in the metazoan kingdom.

PMID- 15578046
TI  - Wolbachia and nuclear-nuclear interactions contribute to reproductive
      incompatibility in the spider mite Panonychus mori (Acari: Tetranychidae).
AB  - Maternally transmitted bacteria of the genus Wolbachia are obligate,
      intracellular symbionts that are responsible for cytoplasmic incompatibility in a
      wide range of arthropods such as insects and mites. Spider mites often show uni-
      and bidirectional incompatibilities among populations with and without Wolbachia.
      Therefore, we surveyed the presence of Wolbachia by PCR and then conducted
      crossing experiments among 25 populations of Panonychus mori to determine how
      Wolbachia are related to the incompatibility in this species. Five out of the 25
      populations were infected with Wolbachia. These five populations were treated
      with an antibiotic (rifampicin) to eliminate Wolbachia. We carried out round
      robin crosses among 20 Wolbachia-uninfected populations, five infected
      populations and five rifampicin-treated populations (30 x 30=900 crosses in
      total). Incompatibility among P. mori populations was caused by Wolbachia
      infection, nuclear-cytoplasmic interactions or nuclear-nuclear interactions.
      Wolbachia-mediated incompatibility was observed in crosses between uninfected
      females and infected males or between females and males harboring different
      Wolbachia strains. Nuclear-cytoplasmic interactions may be responsible for the
      unidirectional incompatibility in crosses between the two northern populations
      and one of the southern populations. Bidirectional incompatibility caused by
      nuclear-nuclear interactions was observed in 99 combinations of interpopulation
      crosses (99/300=0.33). Although no geographical trends were detected in the
      distribution of bidirectionally compatible populations, the results reveal a
      genetic divergence among P. mori populations.

PMID- 15578047
TI  - Mating system of wild Phaseolus lunatus L. and its relationship to population
      size.
AB  - Using isozyme variation in a naturally pollinated seed family for 10 wild
      Phaseolus lunatus L. (Lima bean) populations, ranging in sizes from 10 to 60
      reproductive individuals, we estimated levels of outcrossing (t) and parental
      inbreeding coefficient (F). We also examined the relationship between outcrossing
      rate and population size. Average estimates of the single-locus outcrossing rate
      (ts) ranged from 0.024 to 0.246 (mean=0.091+/-0.065). Estimates of the multilocus
      outcrossing rate (tm) ranged from 0.027 to 0.268, and averaged 0.096+/-0.071.
      Inbreeding coefficients based on genotypic frequencies of maternal plants were
      positive and significantly greater than zero (F=0.504), suggesting an excess of
      homozygotes in all the populations studied. There was indirect evidence of
      nonrandom mating for outcrosses and this was mainly attributed to self
      fertilisation since the averaged difference between tm and ts, which provides a
      measure of biparental inbreeding, represents only 1% of the autogamy rate. No
      significant correlation was observed between outcrossing rate and population
      size. Estimates of t showed significant heterogeneity among populations and
      factors explaining this tendency are suggested.

PMID- 15578048
TI  - Associations between plasma antioxidants and hypertension in a community-based
      sample of 415 Australians aged 60-64.
AB  - It has been suggested that increased oxidative stress may be both a cause as well
      as a consequence of hypertension. In vivo oxidation of low-density lipoproteins
      by oxygen-free radicals may increase hypertension-related atherogenesis, and
      antioxidants may be beneficial in this regard. Previous findings concerning
      associations between serum measures of antioxidants and hypertension have however
      been inconsistent. Plasma levels of beta-carotene, Vitamin A, E, uric acid,
      homocysteine and total antioxidant capacity, as well as two markers of oxidative
      stress, malondialdehyde (MDA) and protein carbonyls, were measured in morning
      fasting blood samples provided by 415 Australians aged 60-64 years, selected
      randomly from the community. Participants also provided information on
      sociodemographic attributes, mental and physical health, and provided two
      measures of resting blood pressure, allowing a diagnosis of definite or
      borderline hypertension. Those with hypertension had lower levels of beta
      carotene and higher levels of uric acid and MDA compared to normotensive
      participants. The last two of these associations persisted when the analyses
      controlled for lifestyle and health factors. The findings from this study offer
      limited support for the proposition that lower antioxidant status and higher
      oxidative stress are associated with hypertension, and suggest the need for
      longitudinal studies to examine causality and intervention studies to determine
      the benefit of antioxidants in this group.

PMID- 15578050
TI  - Just the start.

PMID- 15578049
TI  - Estimation of aortic systolic blood pressure in community-based screening: the
      relationship between clinical characteristics and peripheral to central blood
      pressure differences.

PMID- 15578051
TI  - Hsp90: from structure to phenotype.

PMID- 15578052
TI  - Shortcuts to the end.

PMID- 15578053
TI  - Doing more with less in bacterial DNA repair.

PMID- 15578054
TI  - Wobble during decoding: more than third-position promiscuity.

PMID- 15578056
TI  - A bacterial big-MAC attack.

PMID- 15578058
TI  - Nurturing interdisciplinary research.

PMID- 15578059
TI  - Interdisciplinary research and the undergraduate biology student.

PMID- 15578063
TI  - Externalization of host cell protein kinase C during enteropathogenic Escherichia
      coli infection.
AB  - Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in
      children in developing countries. Protein kinase C (PKC), a serine- and threonine
      directed protein kinase, is rapidly activated following EPEC infection and this
      is accompanied by its translocation to a membrane-bound location where it is
      tightly bound to phosphatidylserine (PS). EPEC infection causes host cell death,
      one of whose features is externalization of PS. We hypothesized that
      externalization of PS would be accompanied by externalization of PKC as well. We
      report that EPEC infection triggers the externalization of PKC to the outer
      surface of the host cell. Ecto-PKC remains firmly tethered to the cell but can be
      released by incubation with peptide or protein substrates for the enzyme. Ecto
      PKC is intact and biologically active and able to phosphorylate protein
      substrates on the surface of the host cell. Phosphorylation of whole EPEC
      bacteria or EPEC-secreted proteins could not be detected. Externalization of PKC
      could be reproduced by the combination of an apoptotic stimulus (ultraviolet (UV)
      irradiation) and phorbol myristate acetate (PMA), a procedure which resulted in
      externalization of >25% of the total cellular content of PKC-alpha. In the
      presence of ATP, ecto-PKC inhibited UV-induced cell shrinkage, membrane blebbing,
      and propidium iodide uptake but not the activation of caspases 3 and 7. This is
      the first report that expression of an ecto-protein kinase is altered by a
      microbial pathogen and the first to note that externalization of PKC can
      accompany apoptosis.

PMID- 15578064
TI  - Novel cationic cardiolipin analogue-based liposome for efficient DNA and small
      interfering RNA delivery in vitro and in vivo.
AB  - Cationic liposomes have been successfully used as an alternative approach to
      viral systems to deliver nucleic acids. However, high toxicity and inconsistent
      transfection efficiency have been associated with the currently available
      liposomes. Therefore, a novel cationic liposome was developed based on a
      synthetic cationic cardiolipin analogue (CCLA) to test the DNA transfection
      efficiency. This CCLA-based liposome was also used to determine the therapeutic
      efficacy of c-raf small interfering RNA (siRNA) in mice. In this report, we
      showed that the CCLA-based liposome was less toxic and effectively transfected
      reporter genes in vitro and in vivo. The transfection efficiency in mice was
      seven-fold higher than the commercially available DOTAP-based liposome. In
      addition, c-raf siRNA in the presence of CCLA-based liposome induced up to 62% of
      growth inhibition in cancer cells. Treatment of c-raf siRNA/CCLA complex in SCID
      mice bearing human breast xenograft tumors resulted in 73% of tumor growth
      suppression as compared to free c-raf siRNA group. In conclusion, a novel CCLA
      based liposome showed less toxicity and broad usage both in vitro and in vivo
      with DNA and siRNA.

PMID- 15578065
TI  - Antitumor effects of radioiodinated antisense oligonuclide mediated by VIP
      receptor.
AB  - A 15-mer phosphorothioate antisense oligonuclide (ASON) complementary to the
      translation start region of the C-myc oncogene mRNA was radioiodinated to enhance
      its antitumor activity, and vasoactive intestinal peptide bound covalently
      polylysine (VIP-polylysine) was used as a carrier to deliver the oligonucleotide
      into VIP receptor-positive tumor cells. The antitumor activity of radioiodinated
      ASON conjugated to VIP-polylysine(VIP-131I-ASON) was investigated in athymic mice
      bearing HT29 tumor xenografts in comparison with unconjugated radioiodinated
      ASON(131I-ASON), unlabelled ASON (VIP-ASON) and scrambled oligonucleotide (VIP
      131I-MON) conjugated to VIP-polylysine. Conjugation 125I-ASON to VIP-polylysine
      resulted in a 5.6-fold decrease in the plasma clearance and a 3.4-fold increase
      in tumor uptake of the radiopharmaceutical. Athymic mice bearing HT29 tumor
      xenografts were treated with 4 weekly doses of VIP-131I-ASON and the antitumor
      effects were assessed by use of the slope of the tumor growth curve. VIP-131I
      ASON exhibited strong antitumor effects against HT29 xenografts, decreasing tumor
      growth rate 9.67-, 7.90-fold more effectively than 131I-ASON and VIP-ASON at
      equivalent doses of ASON. Conversely, 131I-ASON, VIP-ASON or VIP-131I-MON caused
      no significant effect compared with the normal saline. These data indicated that
      use of a VIP-polylysine carrier greatly increased HT29 tumor uptake of ASON and
      treatment with the VIP-131I-ASON complexes resulted in tumor growth delay in
      human colon cancer xenograft.

PMID- 15578066
TI  - Selective induction of cell cycle arrest and apoptosis in human prostate cancer
      cells through adenoviral transfer of the melanoma differentiation-associated -7
      (mda-7)/interleukin-24 (IL-24) gene.
AB  - We have previously reported that overexpression of the melanoma differentiation
      associated gene -7 (mda-7) using a replication-defective adenovirus (Ad-mda7),
      results in tumor-specific growth suppression and induction of apoptosis in wide
      variety of cancer cells. In the present study, we investigated the antitumor
      activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells
      and normal prostate epithelial cells. Overexpression of MDA-7 induced significant
      (P=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU
      145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of
      growth inhibition but not apoptosis was observed. However, the inhibitory effects
      in normal cells were less compared to tumor cells. Growth inhibitory effects were
      mediated by the intracellular and not by extracellular MDA-7 protein. Molecular
      effectors that are involved in Ad-mda7-mediated tumor killing included activation
      of the caspase cascade, and the induction of G2 phase cell cycle arrest through
      the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by
      which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The
      antitumor activity combined with previously reported antiangiogenic and proimmune
      properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of
      primary and disseminated prostate cancer.

PMID- 15578067
TI  - Vascular administration of adenoviral vector soaked in absorbable gelatin sponge
      particles (GSP) prolongs the transgene expression in hepatocytes.
AB  - Transcatheter hepatic arterial chemoembolization using emulsions composed of
      anticancer agents and gelatin sponges (GS) has been an efficient and safe
      palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed
      catheter-mediated left hepatic arterial embolization (CHAE) to increase
      transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion
      was prepared by mixing pieces of GSP and adenoviral vectors expressing
      recombinant beta-galactosidase (Ad.LacZ) or human hepatocyte growth factor
      (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE
      with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ
      activity on day 7. The expression pattern of LacZ staining was either scarce or
      patchy around the central hilum of the hepatic artery, or was homogeneously
      distributed in whole lobes, depending on whether large or small pieces of GSP
      were used. Hematological and serum biochemical changes during CHAE exhibited only
      a few effects. The chronological measurement of serum HGF concentration showed
      that the duration of transgene expression was greater after CHAE with Ad.hHGF. A
      similar pattern of transgene expression was observed in a rat model after hepatic
      arterial embolization with differential doses of Ad.hHGF soaked in GSP. These
      results suggest that hepatic arterial embolization by transcatheter mediated
      infusion with a mixture of adenovirus-GSP could be used for human HCC.

PMID- 15578068
TI  - Successful retrieval of fine-needle aspiration biopsy material from previously
      stained smears for immunocytochemistry: a novel technique applied to three soft
      tissue tumors.
AB  - Fine-needle aspiration biopsies of soft tissue tumors are often not fully
      diagnostic on conventional Papanicolaou or Giemsa stains. Often, more useful
      information can be gleaned from preparing cell blocks, which are amenable to
      immunocytochemistry. However, sufficiently diagnostic cell block material is not
      always forthcoming. We subvent this problem by employing a new 'cytoscrape'
      technique to create cell blocks from previously Papanicolaou-stained smear
      material in two cases of mesenchymal tumors where smear diagnoses were limited to
      'sarcoma, not otherwise specified'. After thorough text and photographic
      documentation of the smear results, the slides were decolorized and tumor cells
      were removed for processing as for routine preparation of cell blocks. Sections
      cut were then submitted for immunocytochemical profiling. This resulted in
      definitive diagnoses in both cases, averting the need for more invasive
      diagnostic procedures. We applied the same technique to a third case of a lung
      nodule, in which the smear was inconclusive and the original cell block
      nondiagnostic. The subsequent immunocytochemical testing enabled a definitive
      diagnosis to be made. This novel technique is described here; its value and
      applicability are discussed in the context of fine-needle aspiration biopsies of
      soft tissue tumors.

PMID- 15578069
TI  - Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly
      identical immunophenotypic profiles.
AB  - Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic
      and immunophenotypic features with plasmablastic plasma cell myeloma. However,
      plasmablastic lymphoma is listed in the World Health Organization (WHO)
      classification as a variant of diffuse large B-cell lymphoma. To characterize the
      relationship between plasmablastic lymphoma and plasmablastic plasma cell
      myeloma, we performed immunohistochemistry using a large panel of B-cell and
      plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of
      plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression
      profiles of the tumor suppressor genes p53, p16, and p27, and the presence of
      Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also
      analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell
      myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20,
      corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly
      positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all
      plasmablastic plasma cell myelomas. Three markers that are often aberrantly
      expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in
      5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic
      plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53,
      and loss of expression of p16 and p27 were present in both tumors. No evidence of
      HHV-8 infection was detected in either neoplasm. The only significant difference
      between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV
      encoded RNA, which was positive in all plasmablastic lymphoma cases tested and
      negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related
      plasmablastic lymphoma have an immunophenotype and tumor suppressor gene
      expression profile virtually identical to plasmablastic plasma cell myeloma, and
      unlike diffuse large B-cell lymphoma. These results do not support the suggestion
      in the WHO classification that plasmablastic lymphoma is a variant of diffuse
      large B-cell lymphoma.

PMID- 15578070
TI  - Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms:
      further evidence from lung tumors.
AB  - Association of X chromosome allelic losses with tumor malignancy has been
      identified in foregut but not in midgut endocrine neoplasms. The aim of this
      study was to investigate the association of deletions on X chromosome with
      malignancy in lung neuroendocrine tumors, another family of foregut neoplasms
      comprising four categories with increased malignancy: typical and atypical
      carcinoids, large cell neuroendocrine and small cell lung carcinomas. To evaluate
      loss of heterozygosity, DNA extracted from nine typical carcinoids, 17 atypical
      carcinoids, six large cell neuroendocrine carcinomas and five small cell lung
      carcinomas was PCR-amplified for 18 microsatellite markers spanning the whole X
      chromosome. All tissue samples were formalin-fixed and paraffin-embedded. X
      chromosome losses were absent in typical carcinoids, whereas they were found in
      nine out of 17 atypical carcinoids and in five out of six large cell
      neuroendocrine carcinomas (involving 28 and 70% of informative loci,
      respectively). On the contrary, deletions on X chromosome were an extremely rare
      event in small cell lung carcinomas. In atypical carcinoids, the presence of
      losses was associated with larger tumor size, higher pT status and advanced
      stage. No death occurred in atypical carcinoid patients without deletions on X
      chromosome, whereas all atypical carcinoid patients who had died from disease
      showed allelic losses. In conclusion, X chromosome allelic losses, absent in
      benign 'typical' carcinoids, progressively increased in frequency from
      intermediate-grade 'atypical' carcinoids to high-grade large cell neuroendocrine
      carcinomas. These results extend the association of deletions on X chromosome
      with malignancy, already demonstrated in other foregut endocrine neoplasms, to
      lung neuroendocrine tumors. The absence of X chromosome allelic losses in small
      cell lung carcinomas underlines a striking difference from large cell
      neuroendocrine carcinomas, possibly linked to different pathogenetic mechanisms
      of these two highly aggressive neuroendocrine lung tumors.

PMID- 15578071
TI  - Lack of association of cytomegalovirus with human brain tumors.
AB  - Cytomegalovirus (CMV) is thought to possess oncogenic properties and has been
      linked with a number of human malignancies. CMV infection was recently described
      in association with malignant gliomas. The intent of the present study was to
      further investigate the reported association between CMV and malignant gliomas.
      Tissue from 22 brain tumors of various histologic types and grades, four normal
      brains, six breast carcinomas, six colon carcinomas, six lung carcinomas, and six
      sarcomas were evaluated for the presence of CMV by polymerase chain reaction
      (PCR), in situ hybridization, and immunohistochemical methods. None of the brain
      tumors or normal brain tissue tested demonstrated evidence of CMV pp65 or early
      nuclear proteins by immunohistochemistry. In addition, no CMV RNA or DNA was
      detected in these cases by in situ hybridization and PCR. None of the carcinomas
      or sarcomas evaluated were positive for CMV by immunohistochemistry, in situ
      hybridization, or PCR. The findings of the present study suggest that CMV is not
      significantly associated with brain tumors in humans.

PMID- 15578072
TI  - Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of
      central nervous system from metastatic clear cell renal cell carcinoma.
AB  - The differential diagnosis between hemangioblastoma of the central nervous system
      and metastatic clear cell renal cell carcinoma can be problematic, because they
      may share striking morphologic similarities. Since CD10 is expressed in clear
      cell renal cell carcinoma, while inhibin alpha is expressed in hemangioblastoma,
      we used CD10 and inhibin alpha (inhibin A) to study their possible use in the
      distinction of these two entities. A total of 22 cases of cerebellar
      hemangioblastoma, five cases of metastatic clear cell renal cell carcinoma to the
      central nervous system, and 16 primary cases of clear cell renal cell carcinoma
      were studied with immunohistochemical staining of both CD10 and inhibin A. All 22
      cases of hemangioblastoma were immunonegative for CD10 in the stromal cells. In
      contrast, all five cases of metastatic clear cell renal cell carcinoma and 16
      cases of primary clear cell renal cell carcinoma showed positive CD10 membranous
      staining. In all, 20 cases of hemangioblastoma (20/22, 91%) expressed inhibin A
      in the stromal cells. Two cases of primary clear cell renal cell carcinoma (2/16,
      13%) and three cases of metastatic clear cell renal cell carcinoma (3/5, 60%)
      showed immunopositivity for inhibin A. In conclusion, in addition to the
      immunostaining of inhibin A, CD10 is a superior marker for distinguishing between
      a hemangioblastoma and a metastatic clear cell renal cell carcinoma.

PMID- 15578073
TI  - Venous congestive myelopathy: a mimic of neoplasia.
AB  - Venous congestive myelopathy is a progressive disorder frequently associated with
      arteriovenous fistulas, usually dural. By causing diffuse spinal cord enlargement
      and enhancement on imaging, it may simulate a neoplasm and prompt a biopsy. We
      evaluated the biopsy findings in seven such patients (M=5, F=2, mean age 59+/-11
      years) who presented variably with progressive lower extremity weakness (86%),
      bowel and bladder dysfunction (86%), sensory changes (86%) or pain (29%).
      Preoperative magnetic resonance imaging showed spinal cord enlargement with T2
      hyperintensity (86%) and contrast enhancement (57%) at the cervical (14%),
      thoracolumbar (57%), and/or conus medullaris (57%) level. Prebiopsy spinal
      angiogram, performed in two patients, was negative. Spinal cord biopsy showed
      architecturally distorted parenchyma with gliosis and thick hyalinized vessels
      (100%), variable myelin loss (71%), mild glial atypia (57%), hemosiderin
      deposition (71%), Rosenthal fibers (43%), vascular thrombosis (29%), and necrosis
      (29%), features highly suggestive of venous congestive myelopathy. Postbiopsy
      spinal angiograms were performed in five patients. A dural arteriovenous fistula
      was identified by selective angiography in three patients, including the two with
      a negative preoperative angiogram. Additional postbiopsy angiographic studies in
      two patients were negative, and two patients were followed up without
      angiography. Mean follow-up after biopsy was 13.6 months. Histologic changes
      characteristic of venous congestive myelopathy may be seen in spinal cord
      biopsies with or without an associated fistula. Recognition of this entity by
      surgical pathologists is important, leading to the correct identification of a
      non-neoplastic lesion as well as of a surgically treatable disease.

PMID- 15578074
TI  - Expression profile and molecular genetic regulation of cyclin D1 expression in
      epithelioid sarcoma.
AB  - Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically
      presenting as a subcutaneous or deep dermal mass in the distal extremities of
      young adults. Molecular genetic data of well-characterized cases of epithelioid
      sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by
      conventional metaphase comparative genomic hybridization reported recurrent gains
      at chromosome 11q13, a region containing many genes, including the cyclin D1
      gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a
      variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The
      objective of this study was to examine cyclin D1 expression in epithelioid
      sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression
      using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by
      immunohistochemistry, were evaluated by fluorescence in situ hybridization (FISH)
      and RNA in situ hybridization (RISH) for amplification of the cyclin D1 gene and
      messenger RNA (mRNA) expression, respectively. Seven of eight cases showed a
      typical eusomic state. One case showed pseudoamplification due to
      aneusomy/polysomy. There was no evidence of cyclin D1 gene amplification or
      messenger RNA overexpression detected by FISH or RNA in situ hybridization
      analyses, respectively. Our data clearly demonstrate that cyclin D1 protein is
      upregulated in epithelioid sarcoma, suggesting a role for this cell cycle
      regulator in the pathogenesis of epithelioid sarcoma. The high level of cyclin D1
      protein expression in epithelioid sarcoma appears to be regulated by
      translational and/or post-translational mechanisms.

PMID- 15578075
TI  - Acute panmyelosis with myelofibrosis: an entity distinct from acute
      megakaryoblastic leukemia.
AB  - The WHO criteria for diagnosing acute panmyelosis with myelofibrosis are somewhat
      distinct from those for acute megakaryoblastic leukemia. However, clinical and
      hematopathologic findings partially overlap. This has raised questions as to
      whether these are indeed separate, definable entities. To determine the potential
      importance of bone marrow biopsy supplemented by immunohistochemistry in
      distinguishing between these two conditions, we studied 17 bone marrow biopsies
      of well-characterized cases of acute panmyelosis with myelofibrosis (six cases)
      and acute megakaryoblastic leukemia (11 cases). We compared blast frequency,
      reticulin content, CD34 expression, and the degree of megakaryocytic
      differentiation of the blast cells in these two conditions. Our results
      demonstrate important differences. Acute panmyelosis with myelofibrosis is
      characterized by a multilineage myeloid proliferation with a less numerous
      population of blasts than acute megakaryoblastic leukemia (P<0.01). In the former
      condition, blasts are always positive with CD34, while in acute megakaryoblastic
      leukemia they express CD34 in 60% of the cases. The blasts in acute panmyelosis
      with myelofibrosis only rarely express megakaryocytic antigens. By contrast,
      acute megakaryoblastic leukemia has a significantly higher proportion of blasts
      expressing megakaryocytic antigens (P<0.01 with CD42b). Our results confirm that
      histology supplemented by immunohistochemistry permits the distinction of these
      conditions in routinely processed bone marrow biopsies.

PMID- 15578076
TI  - Immunohistochemical analysis of PTEN in endometrial carcinoma: a tissue
      microarray study with a comparison of four commercial antibodies in correlation
      with molecular abnormalities.
AB  - The tumor suppressor gene PTEN/MMAC1 is located on chromosome 10q23.3.
      Inactivation of PTEN, either by mutations, deletions, or promoter
      hypermethylation, has been identified in a wide variety of tumors. Inactivation
      of the two alleles of PTEN is required, because it is a tumor suppressor gene.
      Immunohistochemical staining may be an effective screening method to demonstrate
      the absence of the protein in tumors exhibiting PTEN inactivation. We studied a
      tissue microarray, constructed from paraffin-embedded blocks of 95 endometrial
      carcinomas, 38 of them previously evaluated for alterations in PTEN. We also
      studied cell blocks obtained from one PTEN-defective endometrial cancer cell
      line, after transfection with either a plasmid encoding wild-type PTEN or the
      empty vector. The tumor samples were tested with four different anti-PTEN
      commercial antibodies: a polyclonal antibody, the monoclonal antibody 28H6, the
      monoclonal antibody 10P03, and the monoclonal antibody 6.H2.1. Results were
      correlated with the presence of abnormalities in PTEN, as well as with the
      immunohistochemical expression of phosphorylated AKT. Antibody 28H6 produced a
      predominant nuclear staining, while the other three antibodies produced a
      predominant cytoplasmic staining. There was no significant correlation between
      the results obtained with the four antibodies. The monoclonal antibody 6.H2.1 was
      the only one that exhibited a correlation with the presence of molecular
      alterations in PTEN, and a statistically significant association with
      immunostaining for phosphorylated AKT (r=-0.249, P=0.037). The monoclonal
      antibody 10P03 exhibited an association with phospho-AKT that did not have
      statistical significance. Both 6.H2.1 and 10P03 antibodies stained PTEN
      transfected cells, and were negative in the PTEN-deficient cell line blocks. The
      polyclonal antibody and the monoclonal antibody 28H6 produced positive staining
      in PTEN-deficient cell line blocks, suggesting nonspecific staining. The results
      indicate that monoclonal antibody 6.H2.1 may be a suitable alternative for tumors
      with inactivation of PTEN.

PMID- 15578077
TI  - Morphology of colorectal lymphoid aggregates in cancer, diverticular and
      inflammatory bowel diseases.
AB  - The present study compares the characteristics of colorectal lymphoid aggregates
      in patients with carcinoma, diverticular disease, Crohn's disease, or ulcerative
      colitis of the large bowel. A total of 77 patients (41 colorectal cancer, 27
      diverticular disease, six ulcerative colitis, three Crohn's disease) undergoing
      colorectal resection were included. Acetic acid staining, hematoxylin and eosin
      staining, CD3, CD20, and MIB1 immunostaining were employed in order to assess
      density, diameter, subepithelial or basal location, cellular profile, and
      proliferation of lymphoid aggregates in normal-appearing and actively inflamed
      large bowel. In normal-appearing tissue, mean density of lymphoid aggregates was
      lower in patients with ulcerative colitis and Crohn's disease than in those with
      colorectal cancer or diverticular disease. A larger mean diameter of aggregates
      was observed in patients with Crohn's disease. In inflammatory bowel diseases, a
      marked increase of the mean density of lymphoid aggregates was observed in
      actively affected specimens. In Crohn's disease more than in ulcerative colitis,
      the aggregates had a predominant basal or transmural distribution. In
      diverticular disease, active inflammation determined a less significant increase
      of subepithelial aggregates harboring a lower proportion of germinal centers. No
      significant variations of CD3, CD20, and MIB1 were recorded among the four
      disease groups. The lymphoid aggregate derangements observed not only in the
      actively affected mucosa but also in the unaffected colorectal lining of patients
      with Crohn's disease and ulcerative colitis support a relevant involvement of
      lymphoid aggregate system in the pathogenesis of inflammatory bowel diseases.

PMID- 15578078
TI  - Upstaging based solely on positive peritoneal washing does not affect outcome in
      endometrial cancer.
AB  - Surgical staging of endometrial carcinoma includes the collection of peritoneal
      washings in the abdomen and pelvis. A positive finding upstages patients to
      International Federation of Gynecology and Obstetrics stage IIIA. However, the
      prognostic significance of such an upstaging, and thus the justification for the
      routine performance of this procedure, is unclear. This 5-year retrospective
      study was conducted to determine the frequency and prognostic significance of
      upstaging of endometrial carcinoma based solely on positive washings. The cohort
      for the study was collected by review of pathology reports of all washings that
      were performed prior to hysterectomies for suspected endometrial carcinomas over
      a 5-year period (01/1995-12/1999). Cases with positive cytology were selected if
      there was no grossly apparent intraperitoneal disease, no histologic evidence of
      extra-uterine tumor and the cases would otherwise have been considered stage I or
      II (case group). An age-matched control group was selected of stage I and II
      patients with the same histologic subtypes and negative washings (n=19). Of 220
      endometrial carcinomas, peritoneal washing cytology was abnormal in 19 (8.6%) and
      was solely responsible for upstaging only 10 patients (4.5% of all cases, eight
      endometrioid, one-serous, one-mixed; nine stage IA or IB and one stage IIB).
      Adjuvant therapy was administered in 90% of the case group and 74% of the control
      group. After a median follow-up of 51 months (case group) and 63 months (control
      group), we found only a single patient with progression of disease (recurrence,
      metastases or death) in the control group. It is concluded that abnormal cytology
      without other evidence of extrauterine disease leads to upstaging of a minority
      of endometrial carcinoma patients (4.5%), but does not appear to affect their
      overall outcome. Although this is a small single site study, it raises questions
      about the value of this procedure in patients with endometrial cancer.

PMID- 15578079
TI  - Immunohistochemical detection of Ki67 in breast cancer correlates with
      transcriptional regulation of genes related to apoptosis and cell death.
AB  - Ki67 is a nuclear protein that is tightly linked to the cell cycle. It is a
      marker of cell proliferation and has been used to stratify good and poor
      prognostic categories in invasive breast cancer. Its correlation with gene
      expression patterns has not been fully elucidated. In this study, Ki67
      immunohistochemistry using the MIB-1 antibody was performed on sections cut from
      21 formalin-fixed, paraffin-embedded invasive breast cancers. Scoring was
      determined as nil (no immunostaining), low (10% or less immunopositivity) or high
      (>10% immunoreactive cells) respectively. The relationship of Ki67
      immunohistochemical detection with clinicopathologic parameters was evaluated.
      Using Affymetrix U133A GeneChips, expression profiles for these tumors were
      generated and correlated with Ki67 immunohistochemical findings. Analysis of
      variance was used to define genes that were differentially regulated between the
      groups. Real-time polymerase chain reaction (PCR) was used to confirm the
      presence of a downregulated gene. Our results showed high, low and nil Ki67
      immunostaining in nine (43%), six (28.5%) and six (28.5%) invasive breast cancers
      respectively, with increased Ki67 protein expression correlating with high
      histologic grade (P=0.02), mitotic score (P=0.001) and estrogen receptor
      immunonegativity (P=0.002). Expression profiling trends of the Ki67 gene mirrored
      the observed proportions of immunostained cells when the Ki67 immunoscore was
      >10%. Genes related to apoptosis and cell death (bcl2, MAP2K4, TNF10) were noted
      to be downregulated in tumors that disclosed >40% Ki67 immunostaining (P<0.001).
      Downregulation of the bcl2 gene was confirmed at the RNA level by real-time RT
      PCR. Differential regulation of these genes, especially bcl2, may contribute to
      the biological nature of clinically more aggressive and highly proliferative
      breast cancers.

PMID- 15578080
TI  - Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase
      chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in
      HIV-positive patients.
AB  - Human herpesvirus-8 (HHV-8) latency-associated nuclear antigen (LANA) is
      expressed in endothelial and spindle cells of nearly all Kaposi sarcomas, and the
      presence of this antigen in serum is strongly correlated with the risk of
      developing Kaposi sarcoma in immunocompromised individuals. Studies of vascular
      tumors occurring in the general population show LANA expression to be specific
      for Kaposi sarcoma. No study to date, however, has examined whether non-Kaposi
      sarcoma vascular tumors arising in immunocompromised patients may express LANA,
      possibly reflecting origin from an HHV-8-infected endothelial progenitor cell.
      The objective of this study was to evaluate the specificity of LANA expression
      for Kaposi sarcoma in immunocompromised patients by LANA immunohistochemistry and
      real-time polymerase chain reaction (PCR) for HHV-8. A total of 13 cases of non
      Kaposi sarcoma vascular tumors (12 hemangiomas and one epithelioid
      hemangioendothelioma) and 24 cases of Kaposi sarcoma, all from known HIV-positive
      patients, were immunostained for LANA and evaluated for the presence of HHV-8 DNA
      by real-time PCR. LANA expression was seen in 22 of 24 (92%) of Kaposi sarcoma
      cases and in 0 of 13 non-Kaposi sarcoma cases. Real-time PCR detected HHV-8 in
      all of the Kaposi sarcoma cases and in four of the non-Kaposi sarcoma cases (all
      hemangiomas). LANA expression appears to be a highly sensitive and specific
      marker of Kaposi sarcoma in both the general population and in HIV-positive
      patients. This is in contrast to HHV-8 PCR, which is positive in a small subset
      of non-Kaposi sarcoma vascular tumors, most likely due to detection of HHV-8
      within intratumoral blood mononuclear cells by the highly sensitive real-time PCR
      technique. For this reason, LANA immunohistochemistry is preferable to HHV-8 PCR
      for the evaluation of problematic vascular proliferations in HIV-positive
      individuals.

PMID- 15578081
TI  - Improved visual acuity and macular thickness 1 week after intravitreal
      triamcinolone for diabetic macular oedema.
AB  - PURPOSE: To evaluate the clinical and volumetric improvement 1 week after an
      injection of intravitreal triamcinolone acetonide in eyes with diabetic macular
      oedema. METHODS: Seven phakic eyes of seven diabetic patients diagnosed with
      clinically significant macular oedema were treated with a single 4-mg
      intravitreal injection of triamcinolone acetonide (0.1 ml). LogMAR best corrected
      visual acuity (logMAR BCVA), best corrected reading ability (RA), and central
      macular thickness (CMT) with optical coherence tomography (OCT) were assessed
      prior and 1 week subsequent to treatment. RESULTS: Mean improvement in logMAR
      BCVA was 0.146 (P=0.03). Mean reduction in CMT was 150.9 mum (P=0.02, Wilcoxon
      signed-rank test). Mean improvement in RA was 3 lines. CONCLUSION: Reduction in
      macular oedema was demonstrated on OCT at 1 week, in most cases associated with
      improvement in central visual function, in particular, reading ability. Total
      resolution of diabetic macular oedema may occur at 1 week following intravitreal
      steroid injection.

PMID- 15578082
TI  - New South Wales Adult Health Survey 2003.

PMID- 15578083
TI  - Regulation of immunity by lysosphingolipids and their G protein-coupled
      receptors.
AB  - T and B lymphocytes, as well as endothelial cells, express distinctive profiles
      of G protein-coupled receptors for sphingosine 1-phosphate, which is a major
      regulator of T cell development, B and T cell recirculation, tissue homing
      patterns, and chemotactic responses to chemokines. The capacity of drugs that act
      on type 1 sphingosine 1-phosphate receptors to suppress organ graft rejection in
      humans and autoimmunity in animal models without apparent impairment of host
      defenses against infections suggests that this system is a promising target for
      new forms of immunotherapy.

PMID- 15578084
TI  - PPARs in atherosclerosis: the clot thickens.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in Western
      countries. Previous studies have highlighted the beneficial effects of PPARgamma
      activators on cardiovascular disease; however, the role of other PPAR family
      members in atherosclerosis is less clear. A report in this issue of the JCI
      expands our understanding of PPARs in vascular biology and highlights the
      potential use of multiple PPAR agonists to limit lipid accumulation in
      macrophages.

PMID- 15578085
TI  - Fusion of bone marrow-derived stem cells with striated muscle may not be
      sufficient to activate muscle genes.
AB  - Several studies have demonstrated the existence of pluripotent bone marrow
      derived stem cells capable of homing to injured cardiac and skeletal muscle;
      however, there has been little evidence demonstrating the induction of tissue
      specific endogenous genes in donor stem cells following engraftment. A new study
      in this issue reports an intriguing finding that raises additional concerns
      relating to stem cell plasticity and stem cell therapy in an already heated and
      controversial field. The study demonstrates that wild-type bone marrow-derived
      side population stem cells are indeed readily incorporated into both skeletal and
      cardiac muscle when transplanted into mice that lack delta-sarcoglycan -- a model
      of cardiomyopathy and muscular dystrophy. However, these cells fail to express
      sarcoglycan and thus to repair the tissue, which suggests that this stem cell
      population has limited potential for cardiac and skeletal muscle regeneration.

PMID- 15578086
TI  - Marfan syndrome and mitral valve prolapse.
AB  - Mitral valve prolapse (MVP), an abnormal displacement into the left atrium of a
      thickened and redundant mitral valve during systole, is a relatively frequent
      abnormality in humans and may be associated with serious complications. A recent
      study implicates fibrillin-1, a component of extracellular matrix microfibrils,
      in the pathogenesis of a murine model of MVP. This investigation represents an
      initial step toward understanding the mechanisms involved in human MVP disease
      and the development of potential treatments.

PMID- 15578087
TI  - Metabolic fuel selection: the importance of being flexible.
AB  - Studies in genetically engineered mice have shown the importance of cross-talk
      between organs in the regulation of energy metabolism. In this issue, a careful
      metabolic characterization of mice with genetic deficiency of the GLUT4 glucose
      transporter in adipocytes and muscle is reported. These mice compensate for
      decreased peripheral glucose disposal by increasing hepatic glucose uptake and
      lipid synthesis as well as by increasing lipid utilization in peripheral tissues.
      These findings are relevant to humans with type 2 diabetes, in whom a key feature
      is diminished peripheral glucose disposal.

PMID- 15578088
TI  - Cardiac adenoviral S100A1 gene delivery rescues failing myocardium.
AB  - Cardiac-restricted overexpression of the Ca2+-binding protein S100A1 has been
      shown to lead to increased myocardial contractile performance in vitro and in
      vivo. Since decreased cardiac expression of S100A1 is a characteristic of heart
      failure, we tested the hypothesis that S100A1 gene transfer could restore
      contractile function of failing myocardium. Adenoviral S100A1 gene delivery
      normalized S100A1 protein expression in a postinfarction rat heart failure model
      and reversed contractile dysfunction of failing myocardium in vivo and in vitro.
      S100A1 gene transfer to failing cardiomyocytes restored diminished intracellular
      Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ load mechanistically due to
      increased SR Ca2+ uptake and reduced SR Ca2+ leak. Moreover, S100A1 gene transfer
      decreased elevated intracellular Na+ concentrations to levels detected in
      nonfailing cardiomyocytes, reversed reactivated fetal gene expression, and
      restored energy supply in failing cardiomyocytes. Intracoronary adenovirus
      mediated S100A1 gene delivery in vivo to the postinfarcted failing rat heart
      normalized myocardial contractile function and Ca2+ handling, which provided
      support in a physiological context for results found in myocytes. Thus, the
      present study demonstrates that restoration of S100A1 protein levels in failing
      myocardium by gene transfer may be a novel therapeutic strategy for the treatment
      of heart failure.

PMID- 15578089
TI  - Differential inhibition of macrophage foam-cell formation and atherosclerosis in
      mice by PPARalpha, beta/delta, and gamma.
AB  - PPARalpha, beta/delta, and gamma regulate genes involved in the control of lipid
      metabolism and inflammation and are expressed in all major cell types of
      atherosclerotic lesions. In vitro studies have suggested that PPARs exert
      antiatherogenic effects by inhibiting the expression of proinflammatory genes and
      enhancing cholesterol efflux via activation of the liver X receptor-ABCA1 (LXR
      ABCA1) pathway. To investigate the potential importance of these activities in
      vivo, we performed a systematic analysis of the effects of PPARalpha, beta, and
      gamma agonists on foam-cell formation and atherosclerosis in male LDL receptor
      deficient (LDLR(-/-)) mice. Like the PPARgamma agonist, a PPARalpha-specific
      agonist strongly inhibited atherosclerosis, whereas a PPARbeta-specific agonist
      failed to inhibit lesion formation. In concert with their effects on
      atherosclerosis, PPARalpha and PPARgamma agonists, but not the PPARbeta agonist,
      inhibited the formation of macrophage foam cells in the peritoneal cavity.
      Unexpectedly, PPARalpha and PPARgamma agonists inhibited foam-cell formation in
      vivo through distinct ABCA1-independent pathways. While inhibition of foam-cell
      formation by PPARalpha required LXRs, activation of PPARgamma reduced cholesterol
      esterification, induced expression of ABCG1, and stimulated HDL-dependent
      cholesterol efflux in an LXR-independent manner. In concert, these findings
      reveal receptor-specific mechanisms by which PPARs influence macrophage
      cholesterol homeostasis. In the future, these mechanisms may be exploited
      pharmacologically to inhibit the development of atherosclerosis.

PMID- 15578090
TI  - Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression
      after engraftment into cardiac and skeletal muscle.
AB  - Pluripotent bone marrow-derived side population (BM-SP) stem cells have been
      shown to repopulate the hematopoietic system and to contribute to skeletal and
      cardiac muscle regeneration after transplantation. We tested BM-SP cells for
      their ability to regenerate heart and skeletal muscle using a model of
      cardiomyopathy and muscular dystrophy that lacks delta-sarcoglycan. The absence
      of delta-sarcoglycan produces microinfarcts in heart and skeletal muscle that
      should recruit regenerative stem cells. Additionally, sarcoglycan expression
      after transplantation should mark successful stem cell maturation into cardiac
      and skeletal muscle lineages. BM-SP cells from normal male mice were transplanted
      into female delta-sarcoglycan-null mice. We detected engraftment of donor-derived
      stem cells into skeletal muscle, with the majority of donor-derived cells
      incorporated within myofibers. In the heart, donor-derived nuclei were detected
      inside cardiomyocytes. Skeletal muscle myofibers containing donor-derived nuclei
      generally failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers
      detected in the quadriceps muscle from all 14 mice analyzed. Moreover, all
      cardiomyocytes with donor-derived nuclei were sarcoglycan-negative. The absence
      of sarcoglycan expression in cardiomyocytes and skeletal myofibers after
      transplantation indicates impaired differentiation and/or maturation of bone
      marrow-derived stem cells. The inability of BM-SP cells to express this protein
      severely limits their utility for cardiac and skeletal muscle regeneration.

PMID- 15578091
TI  - Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal
      differentiation.
AB  - Hypomorphic mutations in the zinc finger domain of NF-kappaB essential modulator
      (NEMO) cause X-linked hyper-IgM syndrome with ectodermal dysplasia (XHM-ED). Here
      we report that patient B cells are characterized by an absence of Ig somatic
      hypermutation (SHM) and defective class switch recombination (CSR) despite normal
      induction of activation-induced cytidine deaminase (AID) and Iepsilon-Cepsilon
      transcripts. This indicates that AID expression alone is insufficient to support
      neutralizing antibody responses. Furthermore, we show that patient B cells
      stimulated with CD40 ligand are impaired in both p65 and c-Rel activation, and
      whereas addition of IL-4 can enhance p65 activity, c-Rel activity remains
      deficient. This suggests that these NF-kappaB components have different
      activation requirements and that IL-4 can augment some but not all NEMO-dependent
      NF-kappaB signaling. Finally, using microarray analysis of patient B cells we
      identified downstream effects of impaired NF-kappaB activation and candidate
      factors that may be necessary for CSR and SHM in B cells.

PMID- 15578092
TI  - TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor
      antagonist-deficient mice.
AB  - IL-1 receptor antagonist-deficient (IL-1Ra(-/-)) mice spontaneously develop
      autoimmune arthritis. We demonstrate here that T cells are required for the
      induction of arthritis; T cell-deficient IL-1Ra(-/-) mice did not develop
      arthritis, and transfer of IL-1Ra(-/-) T cells induced arthritis in nu/nu mice.
      Development of arthritis was also markedly suppressed by TNF-alpha deficiency. We
      found that TNF-alpha induced OX40 expression on T cells and blocking the
      interaction between either CD40 and its ligand or OX40 and its ligand suppressed
      development of arthritis. These findings suggest that IL-1 receptor antagonist
      deficiency in T cells disrupts homeostasis of the immune system and that TNF
      alpha plays an important role in activating T cells through induction of OX40.

PMID- 15578093
TI  - Novel APC-like properties of human NK cells directly regulate T cell activation.
AB  - Initiation of the adaptive immune response is dependent on the priming of naive T
      cells by APCs. Proteomic analysis of unactivated and activated human NK cell
      membrane-enriched fractions demonstrated that activated NK cells can efficiently
      stimulate T cells, since they upregulate MHC class II molecules and multiple
      ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen
      administration, we show that NK cells possess multiple independent unique
      pathways for antigen uptake. These results highlight NK cell-mediated
      cytotoxicity and specific ligand recognition by cell surface-activating receptors
      on NK cells as unique mechanisms for antigen capturing and presentation. In
      addition, we analyzed the T cell-activating potential of human NK cells derived
      from different clinical conditions, such as inflamed tonsils and noninfected and
      CMV-infected uterine decidual samples, and from transporter-associated processing
      antigen 2-deficient patients. This in vivo analysis revealed that
      proinflammatory, but not immune-suppressive, microenvironmental requirements can
      selectively dictate upregulation of T cell-activating molecules on NK cells.
      Taken together, these observations offer new and unexpected insights into the
      direct interactions between NK and T cells and suggest novel APC-like activating
      functions for human NK cells.

PMID- 15578094
TI  - Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse
      model after rolipram treatment.
AB  - Evidence suggests that Alzheimer disease (AD) begins as a disorder of synaptic
      function, caused in part by increased levels of amyloid beta-peptide 1-42
      (Abeta42). Both synaptic and cognitive deficits are reproduced in mice double
      transgenic for amyloid precursor protein (AA substitution K670N,M671L) and
      presenilin-1 (AA substitution M146V). Here we demonstrate that brief treatment
      with the phosphodiesterase 4 inhibitor rolipram ameliorates deficits in both long
      term potentiation (LTP) and contextual learning in the double-transgenic mice.
      Most importantly, this beneficial effect can be extended beyond the duration of
      the administration. One course of long-term systemic treatment with rolipram
      improves LTP and basal synaptic transmission as well as working, reference, and
      associative memory deficits for at least 2 months after the end of the treatment.
      This protective effect is possibly due to stabilization of synaptic circuitry via
      alterations in gene expression by activation of the cAMP-dependent protein kinase
      (PKA)/cAMP regulatory element-binding protein (CREB) signaling pathway that make
      the synapses more resistant to the insult inflicted by Abeta. Thus, agents that
      enhance the cAMP/PKA/CREB pathway have potential for the treatment of AD and
      other diseases associated with elevated Abeta42 levels.

PMID- 15578095
TI  - Inhibition of apoptosis improves outcome in a model of congenital muscular
      dystrophy.
AB  - The most common form of human congenital muscular dystrophy (CMD) is caused by
      mutations in the laminin-alpha2 gene. Loss of laminin-alpha2 function in this
      autosomal recessive type 1A form of CMD results in neuromuscular dysfunction and,
      often, early death. Laminin-alpha2-deficient skeletal muscles in both humans and
      mice show signs of muscle cell death by apoptosis. To examine the significance of
      apoptosis in CMD1A pathogenesis, we determined whether pathogenesis in laminin
      alpha2-deficient (Lama2(-/-)) mice could be ameliorated by inhibiting apoptosis
      through either (a) inactivation of the proapoptosis protein Bax or (b)
      overexpression of the antiapoptosis protein Bcl-2 from a muscle-specific
      transgene. We found that both of these genetic interventions produced a several
      fold increase in the lifespan of Lama2(-/-) mice. Bax inactivation also improved
      postnatal growth rate and myofiber histology and decreased fixed contractures of
      Lama2(-/-) mice. Thus, Bcl-2 family-mediated apoptosis contributes significantly
      to pathogenesis in the mouse model of CMD1A, and antiapoptosis therapy may be a
      possible route to amelioration of neuromuscular dysfunction due to laminin-alpha2
      deficiency in humans.

PMID- 15578096
TI  - Regulatory T cells can migrate to follicles upon T cell activation and suppress
      GC-Th cells and GC-Th cell-driven B cell responses.
AB  - How Tregs migrate to GCs, and whether they regulate the helper activity of the T
      cells in GCs (GC-Th cells) remains poorly understood. We found a T cell subset in
      human tonsils that displays potent suppressive activities toward GC-Th cell
      dependent B cell responses. These Tregs with the surface phenotype of
      CD4+CD25+CD69- migrate well to CCL19, a chemokine expressed in the T cell zone,
      but poorly to CXCL13, a chemokine expressed in the B cell zone. This migration
      toward the T cell-rich zone rapidly changes to trafficking toward B cell
      follicles upon T cell activation. This change in chemotactic behavior upon
      activation of T cells is consistent with their switch in the expression of the 2
      chemokine receptors CXCR5 and CCR7. CD4+CD25+CD69- Tregs suppress GC-Th cells and
      GC-Th cell-induced B cell responses such as Ig production, survival, and
      expression of activation-induced cytosine deaminase. Our results have identified
      a subset of Tregs that is physiologically relevant to GC-Th cell-dependent B cell
      responses and a potential regulation mechanism for the trafficking of these Tregs
      to GCs.

PMID- 15578097
TI  - TYK2 is a key regulator of the surveillance of B lymphoid tumors.
AB  - Aberrant activation of the JAK-STAT pathway has been implicated in tumor
      formation; for example, constitutive activation of JAK2 kinase or the enforced
      expression of STAT5 induces leukemia in mice. We show here that the Janus kinase
      TYK2 serves an opposite function. Mice deficient in TYK2 developed Abelson
      induced B lymphoid leukemia/lymphoma as well as TEL-JAK2-induced T lymphoid
      leukemia with a higher incidence and shortened latency compared with WT controls.
      The cell-autonomous properties of Abelson murine leukemia virus-transformed (A
      MuLV-transformed) TYK2(-/-) cells were unaltered, but the high susceptibility of
      TYK2(-/-) mice resulted from an impaired tumor surveillance, and accordingly,
      TYK2(-/-) A-MuLV-induced lymphomas were easily rejected after transplantation
      into WT hosts. The increased rate of leukemia/lymphoma formation was linked to a
      decreased in vitro cytotoxic capacity of TYK2(-/-) NK and NKT cells toward tumor
      derived cells. RAG2/TYK2 double-knockout mice succumbed to A-MuLV-induced
      leukemia/lymphoma faster than RAG2(-/-)TYK2(+/-) mice. This defines NK cells as
      key players in tumor surveillance in Abelson-induced malignancies. Our
      observations provide compelling evidence that TYK2 is an important regulator of
      lymphoid tumor surveillance.

PMID- 15578098
TI  - The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody
      induction in Guillain-Barre syndrome.
AB  - Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with
      gangliosides in nervous tissue is considered to induce cross-reactive antibodies
      that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine
      whether specific bacterial genes are crucial for the biosynthesis of ganglioside
      like structures and the induction of anti-ganglioside antibodies, we
      characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and
      control strains. We demonstrated that specific types of the LOS biosynthesis gene
      locus are associated with GBS and with the expression of ganglioside-mimicking
      structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both
      involved in LOS sialylation, expressed truncated LOS structures without sialic
      acid, showed reduced reactivity with GBS patient serum, and failed to induce an
      anti-ganglioside antibody response in mice. We demonstrate, for the first time,
      to our knowledge, that specific bacterial genes are crucial for the induction of
      anti-ganglioside antibodies.

PMID- 15578099
TI  - GLUT4 glucose transporter deficiency increases hepatic lipid production and
      peripheral lipid utilization.
AB  - A critical defect in type 2 diabetes is impaired insulin-stimulated glucose
      transport and metabolism in muscle and adipocytes. To understand the metabolic
      adaptations this elicits, we generated mice with targeted disruption of the GLUT4
      glucose transporter in both adipocytes and muscle (AMG4KO). In contrast to total
      body GLUT4-null mice, AMG4KO mice exhibit normal growth, development, adipose
      mass, and longevity. They develop fasting hyperglycemia and glucose intolerance
      and are at risk for greater insulin resistance than mice lacking GLUT4 in only
      one tissue. Hyperinsulinemic-euglycemic clamp studies showed a 75% decrease in
      glucose infusion rate and markedly reduced 2-deoxyglucose uptake into skeletal
      muscle (85-90%) and white adipose tissue (65%). However, AMG4KO mice adapt by
      preferentially utilizing lipid fuels, as evidenced by a lower respiratory
      quotient and increased clearance of lipids from serum after oral lipid gavage.
      While insulin action on hepatic glucose production and gluconeogenic enzymes is
      impaired, hepatic glucokinase expression, incorporation of 14C-glucose into
      lipids, and hepatic VLDL-triglyceride release are increased. The lipogenic
      activity may be mediated by increased hepatic expression of SREBP-1c and acetyl
      CoA carboxylase. Thus, inter-tissue communication results in adaptations to
      impaired glucose transport in muscle and adipocytes that involve increased
      hepatic glucose uptake and lipid synthesis, while muscle adapts by preferentially
      utilizing lipid fuels. Genetic determinants limiting this "metabolic flexibility"
      may contribute to insulin resistance and type 2 diabetes in humans.

PMID- 15578100
TI  - Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a
      mechanism involving AKT activation and bax translocation.
AB  - Prostaglandin E2 (PGE2) synthesis modulates the response to radiation injury in
      the mouse intestinal epithelium through effects on crypt survival and apoptosis;
      however, the downstream signaling events have not been elucidated. WT mice
      receiving 16,16-dimethyl PGE2 (dmPGE2) had fewer apoptotic cells per crypt than
      untreated mice. Apoptosis in Bax(-/-) mice receiving 12 Gy was approximately 50%
      less than in WT mice, and the ability of dmPGE2 to attenuate apoptosis was lost
      in Bax(-/-) mice. Positional analysis revealed that apoptosis in the Bax(-/-)
      mice was diminished only in the bax-expressing cells of the lower crypts and that
      in WT mice, dmPGE2 decreased apoptosis only in the bax-expressing cells. The HCT
      116 intestinal cell line and Bax(-/-) HCT-116 recapitulated the apoptotic
      response of the mouse small intestine with regard to irradiation and dmPGE2.
      Irradiation of HCT-116 cells resulted in phosphorylation of AKT that was enhanced
      by dmPGE2 through transactivation of the EGFR. Inhibition of AKT phosphorylation
      prevented the reduction of apoptosis by dmPGE2 following radiation. Transfection
      of HCT-116 cells with a constitutively active AKT reduced apoptosis in irradiated
      cells to the same extent as in nontransfected cells treated with dmPGE2.
      Treatment with dmPGE2 did not alter bax or bcl-x expression but suppressed bax
      translocation to the mitochondrial membrane. Our in vivo studies indicate that
      there are bax-dependent and bax-independent radiation-induced apoptosis in the
      intestine but that only the bax-dependent apoptosis is reduced by dmPGE2. The in
      vitro studies indicate that dmPGE2, most likely by signaling through the E
      prostaglandin receptor EP2, reduces radiation-induced apoptosis through
      transactivation of the EGFR and enhanced activation of AKT and that this results
      in reduced bax translocation to the mitochondria.

PMID- 15578101
TI  - A free community approach to classifying disease.

PMID- 15578102
TI  - A 33-year-old man with a facial rash.

PMID- 15578103
TI  - Enzyme replacement in Gaucher disease.

PMID- 15578104
TI  - Using modified antigenic sequences to develop cancer vaccines: are we losing the
      focus?

PMID- 15578105
TI  - Diversity and recognition efficiency of T cell responses to cancer.
AB  - BACKGROUND: Melanoma patients vaccinated with tumor-associated antigens
      frequently develop measurable peptide-specific CD8+ T cell responses; however,
      such responses often do not confer clinical benefit. Understanding why vaccine
      elicited responses are beneficial in some patients but not in others will be
      important to improve targeted cancer immunotherapies. METHODS AND FINDINGS: We
      analyzed peptide-specific CD8+ T cell responses in detail, by generating and
      characterizing over 200 cytotoxic T lymphocyte clones derived from T cell
      responses to heteroclitic peptide vaccination, and compared these responses to
      endogenous anti-tumor T cell responses elicited naturally (a heteroclitic peptide
      is a modification of a native peptide sequence involving substitution of an amino
      acid at an anchor residue to enhance the immunogenicity of the peptide). We found
      that vaccine-elicited T cells are diverse in T cell receptor variable chain beta
      expression and exhibit a different recognition profile for heteroclitic versus
      native peptide. In particular, vaccine-elicited T cells respond to native peptide
      with predominantly low recognition efficiency--a measure of the sensitivity of a
      T cell to different cognate peptide concentrations for stimulation--and, as a
      result, are inefficient in tumor lysis. In contrast, endogenous tumor-associated
      antigen-specific T cells show a predominantly high recognition efficiency for
      native peptide and efficiently lyse tumor targets. CONCLUSIONS: These results
      suggest that factors that shape the peptide-specific T cell repertoire after
      vaccination may be different from those that affect the endogenous response.
      Furthermore, our findings suggest that current heteroclitic peptide vaccination
      protocols drive expansion of peptide-specific T cells with a diverse range of
      recognition efficiencies, a significant proportion of which are unable to respond
      to melanoma cells. Therefore, it is critical that the recognition efficiency of
      vaccine-elicited T cells be measured, with the goal of advancing those modalities
      that elicit T cells with the greatest potential of tumor reactivity.

PMID- 15578106
TI  - Doing new research? Don't forget the old.

PMID- 15578107
TI  - Is the "3 by 5" initiative the best approach to tackling the HIV pandemic?
AB  - BACKGROUND TO THE DEBATE: The World Health Organization (WHO) and its partners
      aim to treat 3 million people infected with HIV in poor and middle income
      countries with antiretroviral treatment by the end of 2005. The ambitious "3 by
      5" initiative has had its supporters and its critics since its announcement in
      2002.

PMID- 15578108
TI  - A national health insurance program for the United States.

PMID- 15578109
TI  - Reconsidering early HIV treatment and supervised treatment interruptions.

PMID- 15578110
TI  - The intangible magic of celebrity marketing.

PMID- 15578111
TI  - Blinding trachoma: a disease of poverty.

PMID- 15578112
TI  - An inflammatory cascade leading to hyperresistinemia in humans.
AB  - BACKGROUND: Obesity, the most common cause of insulin resistance, is increasingly
      recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a
      circulating protein implicated in insulin resistance in rodents, but the role of
      human resistin is uncertain because it is produced largely by macrophages.
      METHODS AND FINDINGS: The effect of endotoxin and cytokines on resistin gene and
      protein expression was studied in human primary blood monocytes differentiated
      into macrophages and in healthy human participants. Inflammatory endotoxin
      induced resistin in primary human macrophages via a cascade involving the
      secretion of inflammatory cytokines that circulate at increased levels in
      individuals with obesity. Induction of resistin was attenuated by drugs with dual
      insulin-sensitizing and anti-inflammatory properties that converge on NF-kappaB.
      In human study participants, experimental endotoxemia, which produces an insulin
      resistant state, causes a dramatic rise in circulating resistin levels. Moreover,
      in patients with type 2 diabetes, serum resistin levels are correlated with
      levels of soluble tumor necrosis factor alpha receptor, an inflammatory marker
      linked to obesity, insulin resistance, and atherosclerosis. CONCLUSIONS:
      Inflammation is a hyperresistinemic state in humans, and cytokine induction of
      resistin may contribute to insulin resistance in endotoxemia, obesity, and other
      inflammatory states.

PMID- 15578113
TI  - From registration to publication.

PMID- 15578114
TI  - Pure red cell aplasia after 13 years of sodium valproate, and bone marrow
      suppression after 17 years of carbamazepine.

PMID- 15578115
TI  - Demographic data and outcome of acute coronary syndrome in the South African
      Asian Indian population.
AB  - Significant differences in the prevalence of coronary heart disease (CHD) exist
      with respect to gender, age and ethnicity. The disease has been reported to be
      higher in Indian populations that have emigrated from the Indian subcontinent.
      The aim of this study was to examine differences in major cardiovascular risk
      factors and clinical outcome in South African Asian Indians of different age
      groups and gender, who presented with acute coronary syndromes (ACS). The study
      cohort consisted of 2 290 consecutive patients, admitted between 1996 and 2002,
      who were divided into three age subgroups: young ( </= 45 years; 20%), middle age
      (> 45 to </= 65 years; 59%), and old age (> 65 years; 21%). All three age groups
      were predominantly male, but this was more evident in the younger (88%) and
      middle age groups (71%), and became less striking as the proportion of females
      increased with age. Smoking was more common in young men compared with young
      women (p < 0.01). Diabetes mellitus (21%) and hypertension (18%) were seen less
      frequently in young patients but this was confined to men only. Total cholesterol
      was elevated in 65 to 70% of all patients while high-density lipoprotein (HDL)
      levels were significantly lower in men compared with women for all age subsets.
      Hospital mortality was extremely low in young (1%) and middle-aged patients (2%),
      but was expectedly higher in older patients (8%; p < 0.0001). A family history of
      CHD was the most common familial vascular disease seen. Young patients were more
      often subjected to diagnostic and therapeutic interventions. They had more
      aggressive disease, with 48% of those subjected to angiographic studies having
      triple vessel disease (TVD), and 14% undergoing coronary artery bypass grafting
      (CABG). Triple vessel disease was also detected most commonly in middle-aged
      (64%) and old patients (75%). In conclusion, significant differences in risk
      factor status were found in South African Indians between genders and for
      different age groups. Also, young Indians in this study differed markedly from
      other young population groups with CHD, in that they frequently had premature
      atherosclerosis with diffuse and aggressive disease.

PMID- 15578116
TI  - Are we faced with two human species?
AB  - Problems could be found in the fact that we very often look for one deciding,
      definitive reason for the process of aging. It is a sort of search for a big
      discovery, like a fountain of youth or such. More and more authors are trying to
      explain the unknowns in the understanding of these observations about aging by
      adding the statement that there are two subgroups in the general population. This
      acknowledgment of two subpopulations explains why there are numerous cases that
      cannot be explained, defined, or fitted in basic observations about caloric
      restrictions and the delay of reproduction. The identification of those two
      groups would allow us to find more realistic results in studies and therefore a
      more efficient therapy of certain diseases. This hypothesis does not contradict
      theories of aging that we have accepted (at least not the majority of accepted
      theories), and this hypothesis also does not contradict the fact that there is a
      large interindividual variability. This hypothesis doubts, and claims there are
      exceptions to, the starting assumption of geriatrics and gerontology that:
      "parallel to the aging process the functions of all organs and organ systems
      lessen."

PMID- 15578117
TI  - Organophosphate nerve agent detection with europium complexes.
AB  - We explore the detection of paraoxon, a model compound for nonvolatile
      organophosphate nerve agents such as VX. The detection utilizes europium
      complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing
      ligands. Both europium luminescence quenching and luminescence enhancement
      modalities are involved in the detection, which is simple, rapid, and sensitive.
      It is adaptable as well to the more volatile fluorophosphate nerve agents. It
      involves nothing more than visual luminescence observation under sample
      illumination by an ordinary hand-held ultraviolet lamp.

PMID- 15578118
TI  - An improved QSPR modeling of hydrocarbon dipole moments.
AB  - Dipole moments of hydrocarbons are not an easy property to model with
      conventional 2D descriptors. A comparison of the performance of the most commonly
      used sets of topological descriptors is presented, each set containing
      descriptors derived from the regular and Detour distance matrix,
      Electrotopological State Indices, and the basic number of atoms of each type and
      bonds. Data were taken on a representative set of 35 hydrocarbon dipole moments
      previously reported and the classical multivariable regression analysis for
      establishing the models is employed.

PMID- 15578119
TI  - Renal pelvis squamous cell carcinoma and renal cell carcinoma in a tuberculous
      kidney.

PMID- 15578120
TI  - Central pain and complex motoric symptoms after gosarelin therapy of prostate
      cancer.
AB  - A 76-year-old man with prostate cancer T3N0M0 and increasing PSA was treated with
      goserelin three times in a half year. As soon as the first treatment, he
      described subjective muscle weakness. After the third treatment, he developed
      complex motoric symptoms and atypical central pain with a likely association to
      goserelin. His left arm had signs of spastic movement; pain deteriorated after
      relaxation. The right hand showed muscle cramps under passive movements of the
      left arm that were not typical for rigor. He felt aching and partial burning pain
      in his whole body. There were few allodynic areas, mainly in the left arm.
      Several treatment approaches failed and the patient died some weeks after the
      first contact with our pain clinic due to pneumonia.

PMID- 15578121
TI  - Retroperitoneal ganglioneuroma encasing the celiac and superior mesenteric
      arteries.
AB  - Ganglioneuroma is a rare neoplasm arising from the sympathoadrenal neuroendocrine
      system and has anatomic distribution paralleling the sympathetic chain ganglia
      and the adrenal medulla. In some cases, ganglioneuroma is the end stage
      maturation of less-differentiated neoplasms such as neuroblastoma or
      ganglioneuroblastoma, but based on age at diagnosis (over 10 years of age) and
      anatomic location, many of these tumors appear to arise de novo. It must be
      included in the differential diagnosis of posterior mediastinal and
      retroperitoneal mass. We report a case of retroperitoneal ganglioneuroma
      involving the celiac axis and superior mesenteric arteries in a 40-year-old
      female.

PMID- 15578122
TI  - Assessing the health effects of long-term exposure to insecticide-treated
      mosquito nets in the control of malaria in endemic regions.
AB  - Malaria is a protozoan disease caused in humans by the genus Plasmodium of which
      four species are known: P. falciparum, P. vivax, P. ovale, and P. malariae. It is
      transmitted through the bite of infected female mosquitoes of the genus
      Anopheles. Malaria is endemic in tropical and subtropical regions of the world.
      It is characterized by extreme exhaustion associated with paroxysms of high
      fever, sweating, shaking chills, and anemia. Approximately 40% of the world''s
      population, mostly those living in the poorest nations, are at risk. Much of the
      deaths due to malaria occur in Africa, mostly among children. The search for
      prevention and control interventions that are effective and sustainable remains
      an abiding challenge for national governments and international health agencies.
      To this end, the World Health Organization and several nongovernmental
      organizations are investing in the use of insecticide-treated mosquito nets
      (ITMNs) as a viable option. Trials of ITMNs in the 1980s and 1990s showed that
      they reduce deaths in young children by an average of 20% and multilateral
      agencies, spearheaded by Roll Back Malaria (RBM), seek to have 60% of the
      populations at risk sleeping under ITMNs by 2005. All pesticides are toxic by
      nature and present risks of adverse effects that depend on toxicity of the
      chemical and the degree of exposure. While there is agreement that ITMNs can be
      effective in reducing malaria morbidity and mortality under field trials, a
      number of factors relating to their sustainability and contribution to health
      improvement in less-developed countries have yet to be determined. In particular,
      the adverse effects associated with their long-term use and misuse has yet to be
      fully evaluated. Although this paper examines potential neurotoxic and
      neurobehavioral effects of long-term use of ITMNs and discusses priority public
      health actions for protecting the health of users, it forms the basis for further
      research.

PMID- 15578123
TI  - An international comparison of women's health issues in the Philippines,
      Thailand, Malaysia, Canada, Hong Kong, and Singapore: the CIDA-SEAGEP Study.
AB  - This was an international study of women's health issues, based on an Official
      Study Tour in Southeast Asia (the Philippines, Thailand, Malaysia, Hong Kong, and
      Singapore) and Canada. The objectives of the study were to identify and compare
      current gaps in surveillance, research, and programs and policies, and to predict
      trends of women's health issues in developing countries based on the experience
      of developed countries. Key informant interviews (senior government officials,
      university researchers, and local experts), self-administered questionnaires,
      courtesy calls, and literature searches were used to collect data. The
      participating countries identified women's health as an important issue,
      especially for reproductive health (developing countries) and senior's health
      (developed countries). Cancer, lack of physical activity, high blood pressure,
      diabetes, poverty, social support, caring role for family, and informing,
      educating, and empowering people about women's health issues were the main
      concerns. Based on this study, 17 recommendations were made on surveillance,
      research, and programs and policies. A number of forthcoming changes in women''s
      health patterns in developing countries were also predicted.

PMID- 15578124
TI  - Towards sustainable use of potassium in pineapple waste.
AB  - Due to the 1997/98 haze problem in South-East Asia and the increasing need for
      sustainable food production and development, the usual management of crop
      residues (including pineapple wastes) through burning is prohibited. As a result,
      the need for alternative uses of pineapple wastes in pineapple production has
      been emphasized. This study investigated an environmentally friendly means of
      recycling pineapple leaves for agricultural use. Pineapple leaves were shredded
      and composted in a composting drum for 30 days. Part of the shredded leaves was
      ashed in a muffle furnace for 4 h. Humic acid (HA), K-fulvate, and K in HA and
      compost were analyzed using standard procedures. An ash to water ratio of 1:7 was
      used to extract 0.1 molar (M) KOH from the shredded leaves. The 0.1 M KOH
      contained 50% K and was able to extract 20% HA from the composted pineapple
      leaves. Percent K in the fulvate using 0.1 M KOH was 43. Besides serving as a
      foliar spray (supplement soil application K fertilizers), source of K for
      freshwater fish (e.g., tilapia), the HA produced can be used as a soil
      conditioner. Studies show that between 0.05-0.01 g of HA per kg soil retards
      runoff by 36% in sandy and sandy loam soils. The K-fulvate can be used as a fluid
      fertilizer. In addition, the pH of 2 of the K-fulvate suggests it could be used
      to dissolve phosphate rocks, particularly those in the arid regions where high
      soil pH does not facilitate the dissolution of these important rocks that serve
      as one of the sources of phosphorus fertilizer in agriculture.

PMID- 15578125
TI  - Extensive urinary system lymphoma delineated by coronal computed tomography.

PMID- 15578126
TI  - Age-related molecular polymorphism of the heterodimeric proteoglycan Bisdermican.
AB  - Bisdermican (PG760) is a large, heterodimeric, dermatan sulfate proteoglycan
      found in selected basement membranes, smooth muscle cell layers, and different
      extracellular matrices. Age-dependent and developmentally regulated alterations
      in glycosaminoglycan structure and quantity have been shown to be functionally
      relevant for a number of physiological and pathological processes. Bisdermican
      was purified from human skin fibroblast cultures of different age and confluency.
      Following beta-elimination, glycosaminoglycan chains were analyzed by Sephacryl-S
      300 chromatography. Glycosaminoglycan chains of Bisdermican from infantile
      fibroblasts had a molecular weight of 19 kDa, whereas the glycosaminoglycan chain
      of the large Bisdermican subunit purified from confluent fetal fibroblast
      secretions was slightly larger (Mr = 24 kDa). Bisdermican derived from
      subconfluent cultures of fetal fibroblasts displayed the largest
      glycosaminoglycan chains with a molecular weight of 31.5 kDa for the large
      subunit, and a molecular weight of 22 kDa for the small subunit. Thus,
      Bisdermican displays a molecular polymorphism that is related to its
      chronological age and proliferative state.

PMID- 15578127
TI  - Skeletal calcium/phosphorus ratio measuring techniques and results. I. Microscopy
      and microtomography.
AB  - An approach to the problem of bone disorders is the measurement of the
      skeleton''s static and dynamic strength, an estimate of which is bone mineral
      density. A decrease in the latter may be due to a decrease in either Ca or P, or
      to dissimilar decreases in both. Consequently, the determination of the Ca/P
      ratio may provide a sensitive measure of bone mineral changes and may add to our
      understanding of the changes occurring in bone diseases. This paper reviews
      techniques such as transmission electron microscopy (TEM) and micro-computed
      tomography (mu-CT), which have been developed for the in vitro assessment of the
      Ca,P content and the skeletal Ca/P ratio. Their main aspects are presented, as
      much as results regarding the referred values. The presentation of other in vitro
      or in vivo techniques, such as instrumental neutron activation analysis (INAA) or
      X-ray absorptiometry accordingly, would be the issue of another article. The
      authors argue that the choice of the best technique relies on its cost ad ease of
      applicability, its reliability, and precision.

PMID- 15578128
TI  - The Canadian Dermatology Workforce Survey: implications for the future of
      Canadian dermatology--who will be your skin expert?
AB  - OBJECTIVE: To survey Canadian dermatologists for specialty-specific physician
      resource information including demographics, workload and future career plans.
      BACKGROUND AND METHODS: In 2001, the Canadian Dermatology Association (CDA)
      surveyed 555 dermatologists in Canada to gain specialty-specific physician
      resource information. Three hundred and seventy-one dermatologists (69%) provided
      information about themselves, their workloads and their future career goals.
      RESULTS: The average Canadian dermatologist is 52 years old and 35% of practicing
      dermatologists are over the age of 55. Eighty-nine percent of dermatologists
      practice in an urban setting, 19% include practice in a rural setting while less
      than 0.5% practice in remote areas. Canadian dermatologists spend 61% of their
      clinical time providing services in Medical Dermatology. Within 5 years, 50% of
      dermatologists reported that they plan to reduce their practices or retire.
      CONCLUSION: The Canadian Dermatology Workforce Survey provides a snapshot of the
      current practice of dermatology in Canada. It also serves to highlight the
      critical shortage of dermatologists, which will continue to worsen without
      immediate, innovative planning for the future.

PMID- 15578129
TI  - Extracorporeal photopheresis differentially regulates the expression of
      phosphorylated STAT-1 and STAT-5 in treated monocytes and T cells, respectively.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) is effective in conditions with
      opposing immune etiology. ECP induces an immunomodulatory response through
      simultaneous monocyte activation and apoptosis induction of lymphocytes. However,
      ECP is also immunosuppressive, downregulating proinflammatory cytokines. Signal
      transducers and activators of transcription (STATs) are important mediators of
      cell-signaling systems, including cytokines. Ultraviolet (UV) immunosuppression
      is linked to reductions in cytokine-induced STAT phosphorylation. OBJECTIVE: The
      aim of this study was to find whether ECP downregulates STAT phosphorylation.
      METHODS: Pre- and post-ECP mononuclear cells from cutaneous T-cell lymphoma and
      chronic graft-versus-host disease patients were stimulated with either IFNbeta,
      IL2, or IL15. The percentage of IFNbeta-stimulated monocytes positive for
      phosphorylated STAT-1 (pSTAT-1) and the number of IL2- and IL15-stimulated T
      cells expressing phosphorylated STAT-5 (pSTAT-5) were determined at 0 and 24 h.
      RESULTS: Post-ECP, pSTAT-1 levels in monocytes remained unchanged; however, at 24
      h post-ECP the number of T cells expressing pSTAT-5 was reduced. CONCLUSION:
      Following ECP, monocytes retain their ability to phosphorylate STAT-1, while
      pSTAT-5 expression is lost in lymphocytes. This differential effect of ECP may
      account for the diverse population of diseases that benefit.

PMID- 15578130
TI  - Supernumerary nipples and renal malformations: a family study.
AB  - We describe a family with supernumerary nipples and kidney and urinary tract
      malformations. The proband is a 59-year-old man with a supernumerary nipple and
      recently identified hypoplastic kidney, bladder diverticulum, and hypotonic
      bladder. His mother also has a supernumerary nipple and a recently identified
      hypoplastic kidney. Of his three children, all male, one has a supernumerary
      nipple but has not been evaluated for a kidney or urinary tract malformation.
      This familial disorder is discussed.

PMID- 15578131
TI  - Annular lichen planus.
AB  - BACKGROUND: Annular lichen planus is a clinical variant of lichen planus, and its
      characteristic lesions are annular plaques consisting of a narrow rim of activity
      and a depressed center. OBJECTIVE: This article presents two cases of annular
      lichen planus, a 39-year-old woman and a 45-year-old woman. METHODS AND RESULTS:
      In both cases, lesions developed mainly on the femoral regions. Histopathological
      specimens from the margin of the lesion demonstrated liquefaction degeneration of
      the epidermis and band-like infiltrate of lymphocytes in the upper dermis,
      whereas there was very mild infiltrate in the upper dermis from the center. In
      the center, elastic fibers were more fragmented and less numerous than in the
      margin. Although topical corticosteroid tape was effective for one case, new
      lesions developed several times over two years in the other. CONCLUSION: Our
      findings suggest that this clinical behavior is from elastolysis as a result of
      inflammation.

PMID- 15578132
TI  - Imaging and percutaneous management of acute complicated pancreatitis.
AB  - Acute pancreatitis varies from a mild, self-limited disease to one with
      significant morbidity and mortality in its most severe forms. While clinical
      criteria abound, imaging has become indispensable to diagnose the extent of the
      disease and its complications, as well as to guide and monitor therapy.
      Percutaneous interventional techniques offer options that can be life-saving,
      surgery-sparing or important adjuncts to operation. Close cooperation and
      communication between the surgeon, gastroenterologist and interventional
      radiologist enhance the likelihood of successful patient care.

PMID- 15578133
TI  - Radiofrequency ablation of lung malignancies: where do we stand?
AB  - Percutaneous radiofrequency (RF) ablation is a minimally invasive technique used
      to treat solid tumors. Because of its ability to produce large volumes of
      coagulation necrosis in a controlled fashion, this technique has gained
      acceptance as a viable therapeutic option for unresectable liver malignancies.
      Recently, investigation has been focused on the clinical application of RF
      ablation in the treatment of lung malignancies. In theory, lung tumors are well
      suited to RF ablation because the surrounding air in adjacent normal parenchyma
      provides an insulating effect, thus facilitating energy concentration within the
      tumor tissue. Experimental studies in rabbits have confirmed that lung RF
      ablation can be safely and effectively performed via a percutaneous,
      transthoracic approach, and have prompted the start of clinical investigation.
      Pilot clinical studies have shown that RF ablation enables successful treatment
      of relatively small lung malignancies with a high rate of complete response and
      acceptable morbidity, and have suggested that the technique could represent a
      viable alternate or complementary treatment method for patients with non-small
      cell lung cancer or lung metastases of favorable histotypes who are not
      candidates for surgical resection. This article gives an overview of lung RF
      ablation, discussing experimental animal findings, rationale for clinical
      application, technique and methodology, clinical results, and complications.

PMID- 15578134
TI  - Microcatheter embolization of lower gastrointestinal hemorrhage: an old idea
      whose time has come.
AB  - Early attempts of using embolization for lower gastrointestinal hemorrhage were
      fraught with complications, most notably ischemic colitis or bowel infarction.
      Embolotherapy was eventually abandoned in favor of catheter-directed
      vasoconstriction (i.e., vasopressin infusion). This latter therapy is time and
      labor intensive. With the advent of microcatheter technology, superselective
      embolization emerged and is rapidly becoming the endovascular therapy of choice
      for patients with severe lower gastrointestinal hemorrhage refractory to medical
      management. Numerous studies on the subject have consistently reported high
      clinical success with low ischemic complications. This article will review the
      current status of co-axial microcatheter embolization with an emphasis on the
      technical aspects of the procedure.

PMID- 15578135
TI  - FEMIC (Fibromes Embolises aux MICrospheres calibrees): uterine fibroid
      embolization using tris-acryl microspheres. A French multicenter study.
AB  - PURPOSE: A French multicenter registry was set up to confirm the safety and
      efficacy of large calibrated tris-acryl gelatin microspheres for embolization of
      symptomatic fibroids. METHODS: Technical recommendations included embolization
      using large microspheres (>500 microm) with no secondary embolization agent.
      Postprocedural pain, clinical improvement and adverse events were prospectively
      evaluated during a follow-up period of at least 6 months. RESULTS: Eighty-five
      women complaining of fibroid-related symptoms entered the study. In seven women,
      a secondary embolization agent was used in addition to microspheres. Complete
      resolution of menorrhagia was achieved in 84% of women at 24 months and
      significant uterine and fibroid volume reductions were noted after 6 months (37%
      and 73%, respectively). Three women experienced definitive amenorrhea (4%) and
      two women required hysteroscopic resection of a fibroid. Eight women were treated
      by hysterectomy because of treatment failure. In seven of these women, treatment
      failure was explained by an additional cause of symptoms including diffuse
      adenomyosis, endometrial hyperplasia or ovarian artery supply to the fibroids.
      CONCLUSION: Limited uterine artery embolization using large microspheres has good
      clinical success rate with low postprocedural pain and complications. Women can
      expect excellent midterm results with a high level of symptom control and
      significant fibroid volume reduction. Confidence in the end-point recommended
      here may require the experience of several cases.

PMID- 15578136
TI  - Endovascular embolization of spontaneous retroperitoneal hemorrhage secondary to
      anticoagulant treatment.
AB  - The purpose of this study was to report a single hospital's experience of
      endovascular treatment of patients with retroperitoneal hemorrhage (RPH)
      secondary to anticoagulant treatment. Ten consecutive patients treated in an
      intensive care unit and needing blood transfusions due to RPH secondary to
      anticoagulation were referred for digital subtraction angiography (DSA) to detect
      the bleeding site(s) and to evaluate the possibilities of treating them by
      transcatheter embolization. DSA revealed bleeding site(s) in all 10 patients: 1
      lumbar artery in 4 patients, 1 branch of internal iliac artery in 3 patients and
      multiple bleeding sites in 3 patients. Embolization could be performed in 9 of
      them. Coils, gelatin and/or polyvinyl alcohol were used as embolic agents.
      Bleeding stopped or markedly decreased after embolization in 8 of the 9 (89%)
      patients. Four patients were operated on prior to embolization, but surgery
      failed to control the bleeding in any of these cases. Abdominal compartment
      syndrome requiring surgical or radiological intervention after embolization
      developed in 5 patients. One patient died, and 2 had sequelae due to RPH. All 7
      patients whose bleeding stopped after embolization had a good clinical outcome.
      Embolization seems to be an effective and safe method to control the bleeding in
      patients with RPH secondary to anticoagulant treatment when conservative
      treatment is insufficient.

PMID- 15578137
TI  - Ultrasound-guided glue injection as alternative treatment of femoral
      pseudoaneurysms.
AB  - The interventional angiographic techniques using the percutaneous femoral
      approach for endovascular revascularization are becoming increasingly more
      popular. These methods usually require larger sheaths, and most patients need
      postprocedural anticoagulation or antiplatelet therapy. As a consequence, the
      interventional procedure is associated with a higher rate of complications at the
      arterial entry site compared to diagnostic angiography. The reported incidence of
      iatrogenic pseudoaneurysm formation after coronary artery interventions ranges
      from 3.2% to 7.7%, and the rates noted after diagnostic angiography range from
      0.2% to 1%.

PMID- 15578138
TI  - Primary stenting of subclavian and innominate artery occlusive disease: a single
      center's experience.
AB  - PURPOSE: To review immediate and midterm results of primary stenting for
      innominate and subclavian artery occlusive lesions. METHODS: Retrospective data
      were collected from 48 consecutive symptomatic patients (27 men and 21 women,
      median age 64 years) having 49 subclavian and innominate artery lesions treated
      with stenting. Of the patients 52% had concomitant ischemic heart disease, and
      30% had carotid and/or vertebral artery disease. Indication for treatment was
      vertebrobasilar insufficiency (VBI) in 16.6% of the patients; upper limb ischemia
      (ULI) in 31.3%; VBI and ULI in 12.5%; transient ischemic attack in 16.7%; angina
      in 12.5% before or after left internal mammary artery-to-coronary artery bypass
      grafting; and leg claudication in 10.4% before or after axillofemoral bypass
      grafting. Balloon-expandable stents were used in 44 lesions and self-expandable
      stents in 5 lesions. In total, 53 stents were placed in 48 patients. RESULTS:
      Technical success was 96%, and clinical success 94%. We encountered four
      complications (two puncture site hematomas, one distal hand embolization and one
      transient cerebral ischemia). Two patients died within 30 days from other causes,
      and seven patients were lost to follow-up. Mean follow-up time was 16.7 months
      (range 0.3 to 68.2). Five patients had recurrent lesions treated by surgical (n =
      2) or endovascular (n = 3) means. Cumulative primary patency rate was 91.7% and
      77% at 12 and 24 months, respectively. Cumulative secondary patency rate was
      96.5% and 91.7% at 12 and 24 months, respectively. CONCLUSION: Stenting of
      subclavian and innominate artery lesions resulted in immediate resolution of
      patients' symptoms with durable midterm effect and few complications in a larger
      patient group with serious comorbid conditions.

PMID- 15578139
TI  - Long-term follow-up of iliac wallstents.
AB  - We evaluated the long-term results of the iliac artery stent placement for the
      treatment of patients with intermittent claudication. From November 1988 to
      December 1998, 303 legs were treated with metal stents in 259 patients with iliac
      occlusive arterial disease in a follow-up study approved by the institutional
      review board. Stenoses (n = 162) were treated after failed angioplasty and
      occlusions (n = 141) were treated with primary stent placement. According to
      Fontaine's clinical classification of chronic ischemia, 266 (88%) legs presented
      stage IIB, 14 (5%) stage III, and 23 (7%) stage IV. In all legs, self-expandable
      stents (Wallstent) were implanted. The patients were followed up with clinical
      examination, ankle brachial- index examination measurement and intravenous
      angiography. The data were analyzed using the univariate analysis (Kaplan-Meier
      method) and multivariate analysis (Cox proportional model). The primary endpoint
      of the study was the identification of restenosis or reoclusion of the stenting
      arterial segment and a secondary endpoint that was an identification of the risk
      factors of restenosis and reoclusion. The mean +/- SD ankle-brachial index pre-,
      post-procedure, and in the last control was 0.58 +/- 0.18, 0.90 +/- 0.23, and
      0.86 +/- 0.24, respectively. Primary cumulative patency rates were 70% +/- 4
      after 5 years, and 65% +/- 5 after 7 years, and secondary patency rates were 92%
      +/- 2 after 5 years, and 87% +/- 4 after 9 years. Immediate complications in the
      first 24 hours appeared in 12 (4%) legs, thrombosis in 5 legs, 3 legs presented
      with distal embolism, 2 thrombi at the access site and pseudo aneurysm and artery
      rupture in 1 leg. A patient died in the first 24 hours. Within 30 days after the
      procedure seven complications, 3 thromboses and 4 stenosis appeared. During
      follow-up, 42 (16%) patients died of other causes. The main causes of death were
      cardiac disease (39%), cerebrovascular disease (15%), cancer (7%), respiratory
      diseases (4%), and death due to accidents (2%), and other causes (9%). In 24% of
      the cases there was insufficient information to assign a principal cause of
      death. Thirty-six patients (13%) were lost to follow-up. Complications arose in
      54 (18%) legs due to occlusion of the treated segment (29%), and stenosis due to
      intimal hyperplasia (27%). Thirteen patients required surgical treatment. Primary
      and secondary patency mean time was 80 +/- 3.7 and 102 +/- 2.4 months,
      respectively. We found no significant relation between patency and the quality of
      run-off, but a small vessel diameter and the female gender were negative
      predictive factors for failure (proportional hazards model). The use of stents
      for treatment of iliac artery occlusive disease may be considered an effective
      method with a low complication rate and acceptable long-term follow-up results.

PMID- 15578140
TI  - The renal impact of aortic stent-grafting in patients with a horseshoe kidney.
AB  - Aortic stent grafting may be an alternative to surgery for patients with an
      abdominal aortic aneurysm and coexistent horseshoe kidney but is not without
      difficulties. This study examines the renal consequences of aortic stent grafting
      in such patients. This is a retrospective review of patients with horseshoe
      kidney in whom aortic stent grafting was performed between December 1995 and
      August 2000. Follow-up occurred within the EUROSTAR protocol and included
      measurement of serum creatinine. Of 130 patients in whom aortic stent grafting
      was performed, 4 had coexistent horseshoe kidney. In all patients the aneurysm
      was successfully excluded with the occlusion of between one and four anomalous
      renal arteries. At follow-up, no clinically significant renal impairment was
      detected. Endovascular aneurysm repair is an attractive option for patients with
      a horseshoe kidney and normal preoperative creatinine levels.

PMID- 15578141
TI  - Endovascular treatment of chronic mesenteric ischemia: results in 14 patients.
AB  - We evaluated immediate and long-term results of percutaneous transluminal
      angioplasty (PTA) and stent placement to treat stenotic and occluded arteries in
      patients with chronic mesenteric ischemia. Fourteen patients were treated by 3
      exclusive celiac artery (CA) PTAs (2 stentings), 3 cases with both Superior
      Mesenteric Artery (SMA) and CA angioplasties, and 8 exclusive SMA angioplasties
      (3 stentings). Eleven patients had atheromatous stenoses with one case of an
      early onset atheroma in an HIV patient with antiphospholipid syndrome. The other
      etiologies of mesenteric arterial lesions were Takayashu arteritis (2 cases) and
      a postradiation stenoses (1 case). Technical success was achieved in all cases.
      Two major complications were observed: one hematoma and one false aneurysm
      occurring at the brachial puncture site (14.3%). An immediate clinical success
      was obtained in all patients. During a follow-up of 1-83 months (mean: 29
      months), 11 patients were symptom free; 3 patients had recurrent pain; in one
      patient with inflammatory syndrome, pain relief was obtained with medical
      treatment; in 2 patients abdominal pain was due to restenosis 36 and 6 months
      after PTA, respectively. Restenosis was treated by PTA (postirradiation
      stenosis), and by surgical bypass (atheromatous stenosis). Percutaneous
      endovascular techniques are safe and accurate. They are an alternative to surgery
      in patients with chronic mesenteric ischemia due to short and proximal occlusive
      lesions of SMA and CA.

PMID- 15578142
TI  - Kinks of the transplant renal artery without accompanying intraarterial pressure
      gradient do not require correction: five-year outcome study.
AB  - Significant transplant renal artery stenosis (TRAS) results in an intraarterial
      pressure gradient and increasing graft dysfunction correctable by endovascular
      therapy. Kinks of the transplant artery cause velocity gradients on Doppler
      ultrasound, but some will have no intraarterial pressure gradient across the
      kink. It is not known whether these nonflow limiting kinks progress further to
      threaten graft function and should undergo endovascular correction. This is a
      longitudinal study of conservatively managed arterial kinks to define their
      natural history. Fourteen patients who had undergone angiography over a 5-year
      period for suspected TRAS had kinks of the renal artery. True intraarterial
      pressures were measured in all cases by slow withdrawal of an end-hole catheter
      after intraarterial injection of a vasodilator. Those with a significant pressure
      change (> or =10% change in peak systolic pressure across the area of suspicion)
      underwent endovascular treatment. The rest were managed conservatively, with
      maximal antihypertensive therapy. Outcome of all 14 cases was determined by
      follow-up of creatinine levels, blood pressure (BP) control and graft outcome
      over a 3-5-year period (median 4 years). Of the 14 patients with kinks, 10 were
      male and 4 female; age range 23-67 years (mean 47 years). Eleven had received
      cadaveric transplants and 3 were allografts; 12 had end-to-side and 2 end-to-end
      anastomosis, 11/14 cases had an intraarterial pressure ratio of <10% and at
      median 4 years follow-up on conservative treatment, the serum creatinine of these
      11 patients did not differ significantly from those who underwent successful
      endovascular treatment (mean 118 micromol/l versus 149 micromol/l; p = 0.30, Mann
      Whitney test). Mean blood pressure was 137/82 mmHg, with a range of 124-155/56-95
      mmHg. Only one patient has required an unexplainable increase in antihypertensive
      medication. Grafts (2/11) were lost and both had chronic rejection on histology.
      There were no unexplained graft failures. Kinks of the renal transplant artery
      with normal intraarterial pressures do not appear to progress and threaten renal
      graft function. Satisfactory graft outcome was seen on 5-year follow-up with
      conservative therapy alone.

PMID- 15578143
TI  - Transcatheter arterial embolization of concurrent spontaneous hematomas of the
      rectus sheath and psoas muscle in patients undergoing anticoagulation.
AB  - We report a case of concurrent rectus sheath and psoas hematomas in a patient
      undergoing anticoagulant therapy, treated by transcatheter arterial embolization
      (TAE) of inferior epigastric and lumbar arteries. Computed tomography (CT)
      demonstrated signs of active bleeding in two hematomas of the anterior and
      posterior abdominal walls. Transfemoral arteriogram confirmed the extravasation
      of contrast from the right inferior epigastric artery (RIEA). Indirect signs of
      bleeding were also found in a right lumbar artery (RLA). We successfully
      performed TAE of the feeding arteries. There have been few reports in the
      literature of such spontaneous hemorrhages in patients undergoing
      anticoagulation, successfully treated by TAE.

PMID- 15578144
TI  - A rare case of jejunal arterio-venous fistula: treatment with superselective
      catheter embolization with a tracker-18 catheter and microcoils.
AB  - Arterio-venous fistulas may develop spontaneously, following trauma or infection,
      or be iatrogenic in nature. We present a rare case of a jejunal arterio- venous
      fistula in a 35-year-old man with a history of pancreatic head resection that had
      been performed two years previously because of chronic pancreatitis. The patient
      was admitted with acute upper abdominal pain, vomiting and an abdominal machinery
      type bruit. The diagnosis of a jejunal arterio-venous fistula was established by
      MR imaging. Transfemoral angiography was performed to assess the possibility of
      catheter embolization. The angiographic study revealed a small aneurysm of the
      third jejunal artery, abnormal early filling of dilated jejunal veins and marked
      filling of the slightly dilated portal vein (13-14 mm). We considered the
      presence of segmental portal hypertension. The patient was treated with coil
      embolization in the same angiographic session. This case report demonstrates the
      importance of auscultation of the abdomen in the initial clinical examination. MR
      imaging and color Doppler ultrasound are excellent noninvasive tools in
      establishing the diagnosis. The role of interventional radiological techniques in
      the treatment of early portal hypertension secondary to jejunal arterio-venous
      fistula is discussed at a time when this condition is still asymptomatic. A
      review of the current literature is included.

PMID- 15578145
TI  - Congenital subclavian artery-to-subclavian vein fistula in an adult: treatment
      with transcatheter embolization.

PMID- 15578146
TI  - Combined use of an occlusion balloon catheter and a microcatheter for
      embolization of the unselectable right inferior phrenic artery supplying
      hepatocellular carcinoma.
AB  - We report the combined use of an occlusion balloon catheter and a microcatheter
      for transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC)
      fed by the unselectable right inferior phrenic artery (IPA). In one case, HCC was
      fed by the reconstructed right IPA via a small branch arising from the proximate
      portion of the celiac artery. In another, the tumor was fed by the right IPA that
      had been previously embolized with coils. TAE was successfully performed through
      a microcatheter placed in the celiac artery immediately proximal to the occluding
      balloon catheter of the celiac trunk and coil embolization of the left gastric
      artery.

PMID- 15578147
TI  - The use of a collagen-based puncture closure device in the subclavian artery
      after inadvertent introduction of an 11.5 French hemodialysis catheter.

PMID- 15578149
TI  - [Prevention and therapy of hemorrhage in the HNO region. Specialist and
      interdisciplinary aspects].
AB  - Otolaryngological bleeding is a highly dangerous condition because it is
      frequently located close to the upper airways. Additionally, it is often
      unexpected, especially in children, and can injure important nervous structures
      of the craniocervical region. Over the years, a broad spectrum of algorithms,
      innovative technologies and therapeutic options have been developed to reduce the
      incidence of hemorrhages and improve therapy. Nowadays, close cooperation with an
      hemostaseologist, anesthesiologist and interventional radiologist is necessary
      for finding the best strategies for the management of bleeding disorders and
      vascular lesions. This interdisciplinary dialog, combined with an intimate
      knowledge of the specific otolaryngological techniques, is the precondition for
      finding an adequate therapy and fulfilling the increasing medico-judicial and
      economic requirements. We present an overview of the actual and proved concepts
      for the management of hemorrhage in order to enable the reader to optimize
      treatment, to increase safety and comfort for the bleeding patient, and to
      fulfill the medico-judicial and economic requirements.

PMID- 15578150
TI  - [Dementia as a primary symptom in late onset multiple sclerosis. Case series and
      review of the literature].
AB  - Cognitive impairment is meanwhile accepted as a well-known symptomatology
      affecting up to 60% of the patients even in the early disease course of multiple
      sclerosis (MS). After a longer duration the development of dementia is not
      unusual. However, cognitive dysfunction as the primary or only manifestation of
      MS is thought to be rare. We report on four elderly patients referred to the
      memory clinic of our psychiatric university hospital because of beginning
      dementia. All of them were found to have evidence of a chronic inflammatory CNS
      process compatible with the diagnosis of MS. At the beginning of their
      symptomatology all patients were older than 60 years . Just in one case,
      progressive gait disturbances beginning after cognitive decline contributed to
      restriction in the activities of daily living. Data of 239 cases of the
      literature were reviewed and revealed motor disturbances as the main initial
      symptom and often a primary progressive course with unfavourable prognosis in
      late onset MS. Until now dementia as the primary symptomatology has not been
      described in patients older than 60 years. Possibly MS as a differential
      diagnosis in dementia as well as cognitive impairment as an initial symptom of MS
      is under-recognized.

PMID- 15578151
TI  - Genetic distances revealed by morphological characters, isozymes, proteins and
      RAPD markers and their relationships with hybrid performance in oilseed rape
      (Brassica napus L.).
AB  - Genetic distances (GDs) based on morphological characters, isozymes and storage
      proteins, and random amplified polymorphic DNAs (RAPD) were used to predict the
      performance and heterosis of crosses in oilseed rape (Brassica napus L.). Six
      male-sterile lines carrying the widely used Shaan2A cytoplasm were crossed with
      five restorer lines to produce 30 F1 hybrids. These 30 hybrids and their parents
      were evaluated for seven agronomically important traits and their mid-parent
      heterosis (MPH) at Yangling, Shaanxi province in Northwest China for 2 years.
      Genetic similarity among the parents based on 34 isozyme and seven protein
      markers was higher than that based on 136 RAPDs and/or 48 morphological markers.
      No significant correlation was detected among these three sets of data.
      Associations between the different estimates of GDs and F1 performance for some
      agronomic traits were significant, but not for seed yield. In order to enhance
      the predicting efficiency, we selected 114 significant markers and 43 favoring
      markers following statistical comparison of the mean values of the yield
      components between the heterozygous group (where the marker is present only in
      one parent of each hybrid) and the homozygous group (where the marker is either
      present or absent in both parents of each hybrid) of the 30 hybrids. Parental GD
      based on total polymorphic markers (GDtotal, indicating general heterozygosity),
      significant markers (GDsign, indicating specific heterozygosity) and favoring
      markers (GDfavor, indicating favoring-marker heterozygosity) were calculated. The
      correlation between GDfavor or GDsign and hybrid performance was higher than the
      correlation between GDtotal and hybrid performance. GDsign and GDfavor
      significantly correlated with plant height, seeds per silique and seed yield, but
      not with the MPH of the other six agronomic traits with the exception of plant
      height. The information obtained in this study on the genetic diversity of the
      parental lines does not appear to be reliable for predicting F1 yield and
      heterosis.

PMID- 15578152
TI  - Assessing temporal changes in genetic diversity of maize varieties using
      microsatellite markers.
AB  - To quantify genetic diversity among modern and earlier maize cultivars, 133
      varieties, representative of the maize grown in France during the last five
      decades, were fingerprinted using 51 SSR. The varieties were grouped into four
      periods. For each period, allelic richness, genetic diversity and genetic
      differentiation among periods were computed. A total of 239 alleles were
      generated. Allelic richness, in terms of number of alleles per locus, for each
      period was 4.5, 3.6, 3.9 and 3.6 respectively. Genetic diversity corresponding to
      Nei's unbiased heterozygosity was calculated, based on allelic frequencies.
      Values ranged from 0.56 to 0.61. Period I presented the highest genetic
      diversity, whereas the three other periods all presented a similar value. A great
      proportion of the total genetic diversity (H(T)=0.59) was conserved within all
      periods (H(S)=0.57), rather than among periods (G(ST)=0.04). The analysis of
      molecular variance showed that the variation among periods represented only 10%
      of the total molecular variation. However, the differentiation among periods,
      although low, was significant, except for the last two periods. Our results
      showed that the genetic diversity has been reduced by about 10% in the maize
      cultivars bred before 1976 compared to those bred after 1985. The very low
      differentiation (G(ST)=0.21%) observed among cultivars of the last two decades
      should alert French maize breeders to enlarge genetic basis in their variety
      breeding programmes.

PMID- 15578153
TI  - Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant
      rats: prevention of diabetes and ectopic lipid deposition.
AB  - AIMS/HYPOTHESIS: Leptin has been shown to activate AMP-activated protein kinase
      (AMPK), an enzyme that regulates the activities of key enzymes of lipid synthesis
      and metabolism. We assess here (i) whether AMPK activity is diminished in rodents
      deficient in leptin or the leptin receptor, and (ii) the effects of treating the
      diabetes-prone, leptin-receptor-deficient Zucker Diabetic Fatty (ZDF) rat with an
      AMPK activator. METHODS: AMPK activity and related parameters were measured in
      muscle and or liver of fa/fa and ZDF rats and ob/ob mice. We also explored the
      effect of treatment with the AMPK activator 5-aminoimidazole 4-carboxamide 1-beta
      D ribofuranoside (AICAR) (7.4 mmol/l, on Monday, Wednesday and Friday for 15
      weeks, beginning at 7 weeks of age) on the phenotype of the ZDF rat. RESULTS:
      AMPK activity was diminished in muscle and/or liver of fa/fa (leptin-receptor
      deficient, non-diabetic) and ZDF (leptin-receptor-deficient, diabetes-prone) rats
      and ob/ob mice (leptin-deficient). ZDF rats that had free access to food became
      hyperglycaemic (22.2 mmol/l) and hyperphagic after 2 to 5 weeks and remained so
      during the remainder of the study. Treatment of ZDF rats with AICAR prevented the
      development of diabetes, as well as increases of triglyceride content in liver,
      muscle and the pancreatic islets. It also attenuated the morphological
      abnormalities observed in the islets of untreated rats. Rats diet-matched with
      the AICAR-treated animals developed diabetes of intermediate severity and showed
      decreases in triglyceride content in the islets, but not in liver or muscle.
      CONCLUSIONS/INTERPRETATION: The results indicate that a deficiency of leptin or
      the leptin receptor is associated with a decrease in AMPK activity in muscle
      and/or liver. They also suggest that treatment with an AMPK activator prevents
      the development of diabetes and ectopic lipid accumulation in the ZDF rat.

PMID- 15578154
TI  - Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta
      mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated
      proapoptotic pathways.
AB  - AIMS/HYPOTHESIS: The proinflammatory cytokine IL-1beta induces apoptosis in
      pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF
      kappaB), mitogen-activated protein kinase, and protein kinase C. We recently
      showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative
      feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets
      and beta cell lines, preventing their deleterious effects. However, the
      mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention
      against apoptosis remain unknown. METHODS: The effect of SOCS-3 expression on the
      global gene-expression profile following IL-1beta exposure was microarray
      analysed using a rat beta cell line (INS-1) with inducible SOCS-3 expression.
      Subsequently, functional analyses were performed. RESULTS: Eighty-two known genes
      and several expressed sequence tags (ESTs) changed expression level 2.5-fold or
      more in response to IL-1beta alone. Following 6 h of IL-1beta exposure, 23
      transcripts were up-regulated. Of these, several, including all eight transcripts
      relating to immune/inflammatory response pathways, were suppressed by SOCS-3.
      Following 24 h of IL-1beta exposure, secondary response genes were detected,
      affecting metabolism, energy generation, protein synthesis and degradation,
      growth arrest, and apoptosis. The majority of these changes were prevented by
      SOCS-3 expression. Multiple IL-1beta-induced NF-kappaB-dependent proapoptotic
      early response genes were inhibited by SOCS-3 expression, suggesting that SOCS-3
      inhibits NF-kappaB-mediated signalling. These observations were experimentally
      confirmed in functional analyses. CONCLUSIONS/INTERPRETATION: This study suggests
      that there is an unexpected cross-talk between the SOCS/IFN and the IL-1beta
      pathways of signalling in pancreatic beta cells, which could lead to a novel
      perspective of blocking two important proapoptotic pathways in pancreatic beta
      cells by influencing a single signalling molecule, namely SOCS-3.

PMID- 15578155
TI  - Risk factors for late-onset ventilator-associated pneumonia in trauma patients
      receiving selective digestive decontamination.
AB  - OBJECTIVE: To determine the independent risk factors for late-onset ventilator
      associated pneumonia (VAP) in trauma patients receiving selective digestive
      decontamination (SDD). DESIGN: A 4-year, prospective cohort study of trauma
      patients meeting the following criteria: injury severity score >15, and duration
      of mechanical ventilation >5 days. Predictors of late-onset VAP occurrence were
      assessed by logistic regression analysis. POPULATION: All patients received SDD
      consisting of polymixin E, gentamicin, and amphotericin B applied in nostrils,
      mouth, and gut with a 3-day course of parenteral cefazolin. VAP was suspected on
      clinical and radiological signs, and confirmed by the presence of at least one
      microorganism at a concentration of at least 10(4) CFU/ml on the broncho-alveolar
      lavage. MEASUREMENT: Independent risk factors for late-onset VAP. RESULTS: A late
      onset VAP was diagnosed in 90 (56%) out of 159 patients. Predicting factors for
      late-onset VAP were: use of non-depolarizing muscle relaxant agents for
      intubation [3.4 (CI 1.08-10.73)], duration of intubation [1.06 (CI 1.01-1.17)],
      length of intensive care unit (ICU) stay [1.05 (CI 1.02-1.09)], and prior
      tracheal colonization [1.03 (CI 1.02-1.21)]. Exposure to prior antimicrobial
      treatment, except SDD, conferred protection [0.3 (0.12-0.74)]. CONCLUSION: This
      study confirms the role of duration of intubation, length of ICU stay, and prior
      tracheal colonization in the development of late-onset VAP. The results also
      highlight the importance of the initial management on the development of late
      onset VAP. The type of neuromuscular blocking agents to intubate trauma patients
      should be evaluated in future studies.

PMID- 15578156
TI  - Survey of the characteristics and satisfaction degree of the patients using a
      pessary.
AB  - The objective of this study was to evaluate characteristics, satisfaction degree,
      and problems of patients using a pessary for pelvic organ prolapse. A total of
      104 patients who had been fitted with a pessary and available for follow-up for
      pelvic organ prolapse management were enrolled. The patients answered questions
      on general characteristics, indications for pessary use, complications from
      pessary use, satisfaction degree, and frequency of removal. The results indicated
      that 76 (73.0%) patients had at least more than one medical illness and 86
      (82.7%) patients complained of lower urinary symptoms such as incontinence,
      urgency, frequency, or nocturia. Eighty-four (80.7%) patients used pessaries as
      they were not surgical candidates due to poor medical status or old age. After
      using a pessary, 76 (73.1%) patients had symptoms such as bleeding, erosion, or
      foul odor; 70.2% of the women answered that they were satisfied or more than
      satisfied and 19.1% of the patients removed their pessaries, of whom 80.0% were
      unable to continue use due to repeated expulsion of the pessary and uncomfortable
      fitting. These data suggest that the pessary tends to be used for high-risk
      patients due to medical problems or old age. Despite the high frequency of
      complications from pessary use, it was seen that the frequency of removing the
      pessary was low and the satisfaction degree was high. Most of the complications
      were not thought to be serious. To decrease the frequency of complications, the
      regular follow-up visit and proper management of pessary use were thought to be
      needed. Further studies are warranted on tailor-fitting the pessary by variable
      use and relieving the symptoms associated with the lower urinary tract.

PMID- 15578157
TI  - Strontium ranelate: a novel mode of action leading to renewed bone quality.
AB  - Various bone resorption inhibitors and bone stimulators have been shown to
      decrease the risk of osteoporotic fractures. However, there is still a need for
      agents promoting bone formation by inducing positive uncoupling between bone
      formation and bone resorption. In vitro studies have suggested that strontium
      ranelate enhances osteoblast cell replication and activity. Simultaneously,
      strontium ranelate dose-dependently inhibits osteoclast activity. In vivo studies
      indicate that strontium ranelate stimulates bone formation and inhibits bone
      resorption and prevents bone loss and/or promotes bone gain. This positive
      uncoupling between bone formation and bone resorption results in bone gain and
      improvement in bone geometry and microarchitecture, without affecting the
      intrinsic bone tissue quality. Thus, all the determinants of bone strength are
      positively influenced. In conclusion, strontium ranelate, a new treatment of
      postmenopausal osteoporosis, acts through an innovative mode of action, both
      stimulating bone formation and inhibiting bone resorption, resulting in the
      rebalancing of bone turnover in favor of bone formation. Strontium ranelate
      increases bone mass while preserving the bone mineralization process, resulting
      in improvement in bone strength and bone quality.

PMID- 15578158
TI  - Clinical effects of strontium ranelate in women with postmenopausal osteoporosis.
AB  - Postmenopausal osteoporosis has long-term physical, psychological, and social
      consequences with a major impact on patients' daily life. Treatment for such a
      chronic disease needs to be clinically effective and well tolerated, and should
      ultimately result in a beneficial effect on quality of life. The antifracture
      efficacy of strontium ranelate, 2 g/day orally, an agent that appears to have
      dissociation effects on resorption and formation, has been assessed in two large,
      randomized, double-blind, placebo-controlled clinical studies: the Spinal
      Osteoporosis Therapeutic Intervention (SOTI) trial and the TReatment Of
      Peripheral Osteoporosis Study (TROPOS), including more than 6,700 postmenopausal
      women. Pending the results of TROPOS, a 3-year analysis of SOTI results shows
      that strontium ranelate significantly reduces new vertebral and clinical
      vertebral fracture incidence in postmenopausal osteoporotic women. This
      significant reduction in the risk of clinical and new vertebral fractures has
      been demonstrated as early as after 1 year of treatment (RR = 0.48, p = 0.003;
      and RR = 0.51, p < 0.001, respectively) and is maintained over 3 years (RR =
      0.62, p < 0.001; and RR = 0.59, p < 0.001, respectively). This is accompanied by
      decreased back pain and body height loss in the strontium ranelate group compared
      with the placebo group. As strontium ranelate appears to improve clinical signs
      and is, furthermore, well tolerated especially in the upper gastrointestinal
      region, this treatment is expected to result in an improved health-related
      quality of life (HRQoL). Strontium ranelate thus offers significant clinical
      benefits in terms of efficacy, tolerability, and ease of administration in the
      treatment of postmenopausal women with vertebral osteoporotic fractures.

PMID- 15578159
TI  - Strontium ranelate: a novel mode of action optimizing bone formation and
      resorption.
AB  - Strontium ranelate has been shown to decrease the risk of fractures in
      postmenopausal women. Its efficacy in clinical studies results from its unique
      mode of action, on both bone resorption and bone formation. Pharmacological
      studies in animals have shown that strontium ranelate decreases bone resorption
      and increases bone formation, resulting in increased bone mass. In ovariectomized
      rats, strontium ranelate prevented the reduction in bone mineral content and the
      decrease in trabecular bone volume induced by estrogen deficiency. In this model,
      strontium ranelate decreased bone resorption, whereas bone formation was
      maintained at a high level as documented by plasma biochemical markers and
      histomorphometric indices of bone formation. In the model of osteopenia induced
      by hind-limb immobilization in rats, strontium ranelate reduced histomorphometric
      parameters of bone resorption and partially prevented long-bone loss, as assessed
      by bone mineral content, bone volume, and biochemical indices of bone resorption.
      In intact mice, strontium ranelate increased bone formation and vertebral bone
      mass. In intact growing rats, strontium ranelate increased the bone trabecular
      volume without alteration of mineralization. The unique mode of action of
      strontium ranelate on bone formation and resorption was supported by in vitro
      studies. In rat calvaria culture systems and rat osteoblastic cell cultures,
      strontium ranelate enhanced preosteoblastic cell replication and increased
      collagen synthesis by osteoblasts. Moreover, strontium ranelate decreased bone
      resorption in organ cultures and decreased the resorbing activity of isolated
      mouse osteoclasts. The assessment of bone markers in a clinical trial [Spinal
      Osteoporosis Therapeutic Intervention (SOTI)] supports the mode of action of
      strontium ranelate: bone alkaline phosphatase levels increased and C-telopeptide
      of type I collagen levels decreased in treated patients compared with the placebo
      group at all time points. Thus, pharmacological and clinical studies suggest that
      strontium ranelate optimizes bone resorption and bone formation, resulting in
      increased bone mass, which may be of great value in the treatment of
      osteoporosis.

PMID- 15578160
TI  - Isolation and characterisation of an equol-producing mixed microbial culture from
      a human faecal sample and its activity under gastrointestinal conditions.
AB  - Only about one third of humans possess a microbiota capable of transforming the
      dietary isoflavone daidzein into equol. Little is known about the dietary and
      physiological factors determining this ecological feature. In this study, the in
      vitro metabolism of daidzein by faecal samples from four human individuals was
      investigated. One culture produced the metabolites dihydrodaidzein and O
      desmethylangolensin, another produced dihydrodaidzein and equol. From the latter,
      a stable and transferable mixed culture transforming daidzein into equol was
      obtained. Molecular fingerprinting analysis (denaturing gradient gel
      electrophoresis) showed the presence of four bacterial species of which only the
      first three strains could be brought into pure culture. These strains were
      identified as Lactobacillus mucosae EPI2, Enterococcus faecium EPI1 and
      Finegoldia magna EPI3, and did not produce equol in pure culture. The fourth
      species was tentatively identified as Veillonella sp strain EP. It was found that
      hydrogen gas in particular, but also butyrate and propionate, which are all
      colonic fermentation products from poorly digestible carbohydrates, stimulated
      equol production by the mixed culture. However, when fructo-oligosaccharides were
      added, equol production was inhibited. Furthermore, the equol-producing capacity
      of the isolated culture was maintained upon its addition to a faecal culture
      originating from a non-equol-producing individual.

PMID- 15578161
TI  - Novel methods for analysis of genomic DNA methylation.

PMID- 15578162
TI  - An extensive colour palette in Roman villas in Burgos, Northern Spain: a Raman
      spectroscopic analysis.
AB  - Seventy-five specimens from thirty fragments of Roman villa wall-paintings from
      sites in Burgos Castilla y Leon, Spain, have been analysed by Raman spectroscopy.
      This is the first time that a Raman spectrocopic study of Roman wall-paintings
      from Spain has been reported. The extensive range of tonalities and colour
      compositions contrasts with the results found in other provinces of the Roman
      Empire, for example Romano-British villas. Calcite, aragonite, haematite, caput
      mortuum, cinnabar, limonite, goethite, cuprorivaite, lazurite, green earth,
      carbon and verdigris have been found as pigments. Some mineral mixtures with
      different tonalities have been made using different strategies to those more
      usually found. Of particular interest is the assignation of the Tarna mine for
      the origin of the cinnabar used for obtaining the red colour in some specimens
      analysed here. The wide range of colours, tonalities and minerals found in some
      of the sites studied in this work is suggestive of a high social status for the
      community.

PMID- 15578163
TI  - Solvent extraction and extraction-voltammetric determination of phenols using
      room temperature ionic liquid.
AB  - The phenolic compounds phenol, 4-nitrophenol, 2,4-dinitrophenol, 2,6
      dinitrophenol, 1-naphthol, 2-naphthol, and 4-chlorophenol are extracted nearly
      quantitatively from aqueous solution into the room temperature ionic liquid 1
      butyl-3-methylimidazolium hexafluorophosphate (BMImPF6) in molecular form at pH <
      p Ka. Picric acid is extracted efficiently in anionic form. Recovery of
      pyrocatechol and resorcinol is much lower. The effect of pH, phenol
      concentration, and volume ratio of aqueous and organic phases were studied. Ionic
      liquid BMImPF6 is shown to be suitable for extraction-voltammetric determination
      of phenols without back-extraction or addition of support electrolyte. The
      electrochemical window of BMImPF6 at various electrodes was determined, and
      voltammetric oxidation of phenols and reduction of nitrophenols in BMImPF6 was
      studied.

PMID- 15578164
TI  - Liquid chromatography-mass spectrometry in peptide drug discovery and
      development.

PMID- 15578165
TI  - Selectivity of long chain stationary phases in reversed phase liquid
      chromatography.
AB  - A series of commercial monomeric and polymeric C(18), C(27), and C(30) stationary
      phases were compared with immobilized poly(ethylene-co-acrylic acid) stationary
      phases synthesized in-house. The columns were characterized on the basis of
      methylene selectivity, silanol activity, metal activity, pore size, shape
      selectivity, and the ability to separate tocopherol isomers and carotenoid
      isomers. Monomeric and polymeric C(30) phases were shown to yield excellent
      separations of the tocopherol isomers while the polymeric C(30) and polyethylene
      phases were more appropriate to the separation of carotenoids.

PMID- 15578166
TI  - Preparation of trout liver microsomes for iron speciation in P-450 enzymes by AE
      FPLC with ICP-(ORS)MS detection.
AB  - Cytochromes P-450 are members of a superfamily of hemoproteins involved in the
      oxidative metabolism of various physiological and xenobiotic compounds in
      eukaryotes and prokaryotes. The multiplicity of this group of enzymes has been
      widely studied by chromatographic techniques, mainly high-performance liquid
      chromatography (HPLC). Because these enzymes are membrane-bound proteins, sample
      preparation for chromatographic separation of P-450 enzymes requires a
      solubilization step. The sample-preparation procedures are critical, because
      detergents affect not only the efficiency of protein solubilization but also
      their further chromatographic resolution. Trout liver microsomes have been taken
      here as a model sample to investigate iron speciation in cytochrome P-450. Trouts
      were treated intraperitoneally with beta-naphthoflavone, a potent inducer of some
      P-450 enzymes, and a microsomal suspension containing 7.4+/-0.1 nmol mL(-1) P-450
      enzymes was obtained by ultracentrifugation. Lubrol PX was selected as detergent
      for solubilization, resulting in about 90% solubilization recovery. The
      solubilized cytochromes P-450 were further separated by AE-FPLC, with UV
      detection, or coupled to ICP-MS with an octapole reaction system, ICP-(ORS)MS
      (monitoring Fe signals at masses 54, 56, and 57). A sampling procedure and
      chromatographic conditions are developed and were successfully applied to iron
      speciation in trout liver P-450 enzymes. ICP-(ORS)MS detection of P-450 enzymes
      is Fe-specific and so will give accurate information on the prosthetic group of
      the protein, which can constitute an advantageous alternative to classical
      methods for detection of these hemoproteins.

PMID- 15578167
TI  - Processing of a simple aversive conditioned stimulus in a divided visual field
      paradigm: an fMRI study.
AB  - A left visual hemifield advantage for the processing of negative facial
      expressions has been demonstrated in a variety of studies. We tested whether the
      same effect is found for a neutral facial expression that had acquired a negative
      meaning through pairing with an aversive event. Startle reflex amplitudes, skin
      conductance responses (SCR), and two verbal measures of affect (negative valence
      and arousal) were significantly increased after pairing, but no stimulation side
      by pairing interaction was observed. Functional magnetic resonance imaging (fMRI)
      revealed a significant increase of BOLD (blood oxygen level dependent) activity
      in the medial prefrontal cortex (MPFC), and the right frontal opercular region
      (RFOP). MPFC activity was correlated with psychophysiological and verbal
      emotional responses across subjects and, like these responses, was independent of
      the stimulation side. In contrast, RFOP activity was significantly stronger
      during left than during right hemifield stimulation but did not correlate with
      psychophysiological or verbal measures of negative affect. These results suggest
      that emotional responses to an aversive conditioned expressively neutral face are
      similar in both visual hemifields. MPFC activity seems to be closely linked to
      the strength of these responses.

PMID- 15578168
TI  - Perceptual learning of line orientation modifies the effects of transcranial
      magnetic stimulation of visual cortex.
AB  - Perceptual learning may be accompanied by physiological changes in early visual
      cortex. We used transcranial magnetic stimulation (TMS) to test the postulate
      that perceptual learning of a visual task initially performed at 60-65% accuracy
      strengthens visual processing in early visual cortex. Single pulse TMS was
      delivered to human occipital cortex at time delays of 70-154 ms after the onset
      of an odd-element, line orientation discrimination task. When TMS was delivered
      at a delay of 84 ms or later the accuracy of visual discrimination was
      transiently degraded in ten subjects. As visual performance in control trials
      without TMS improved with training, the absolute magnitude of TMS suppression of
      performance decreased in parallel. This result occurred both when TMS was
      delivered to broad areas of occipital cortex and when TMS was optimally delivered
      to early occipital cortex. No change in TMS suppression was observed when three
      new subjects were given feedback during an odd-element task that did not require
      substantial perceptual learning. Thus, perceptual learning improved visual
      performance and reduced TMS suppression of early visual cortex in parallel.

PMID- 15578169
TI  - Spatiotemporal characteristics of the neural activities processing
      consonant/dissonant tones in melody.
AB  - To identify neural correlates underlying melody processing, we measured MEG
      responses elicited by keynote and out-of-key tones at the end of musical phrases.
      These melodies were newly composed and unknown to the subjects. Significant
      enlargements of N1m/P2m peaks at about 120-160 ms were observed in response to
      dissonant (out-of-key) tones compared to those in response to consonant (keynote)
      tones. The equivalent current dipoles (ECD) of the N1m were localized in areas
      centered at bilateral primary auditory cortices in the superior surface of the
      temporal lobe. Following the N1m/P2m, a late component occurring at 280-530 ms
      was observed. As the latency proceeded, the location of ECD sources of the late
      component shifted in the right hemisphere, but not in the left hemisphere, from
      the supratemporal auditory cortex to a posterior inferior auditory association
      cortex around the superior temporal sulcus (STS). The grand mean locations of the
      ECDs for consonant and dissonant tones were separated at a peak period of 380-410
      ms of the late component but converged to the same region around the STS in the
      last period of 440-530 ms. These observations suggest that the neural activities
      generating the N1m component in the bilateral auditory cortices may play a role
      in automatic detection of tonality mismatch based on the pitch analysis. The
      activities of the late component around the posterior part of the right STS are
      thought to be involved in the analysis of pitch-sequence, such as how the pitch
      changes temporally, as a pre-process of melody perception.

PMID- 15578170
TI  - Accuracy of spatial localization depending on head posture in a perturbed
      gravitoinertial force field.
AB  - Spatial orientation is crucial when subjects have to accurately reach memorized
      visual targets. In previous studies modified gravitoinertial force fields were
      used to affect the accuracy of pointing movements in complete darkness without
      visual feedback of the moving limb. Target mislocalization was put forward as one
      hypothesis to explain this decrease in accuracy of pointing movements. The aim of
      this study was to test this hypothesis by determining the accuracy of spatial
      localization of memorized visual targets in a perturbed gravitoinertial force
      field. As head orientation is involved in localization tasks and carrying
      relevant sensory systems (visual, vestibular and neck muscle proprioceptive), we
      also tested the effect of head posture on the accuracy of localization. Subjects
      (n=10) were seated off-axis on a rotating platform (120 degrees s(-1)) in
      complete darkness with the head fixed (head-fixed session) or free to move (head
      free session). They were required to report verbally the egocentric spatial
      localization of visual memorized targets. They gave the perceived target location
      in direction (i.e. left or right) and in amplitude (in centimeters) relative to
      the direction they thought to be straight ahead. Results showed that the accuracy
      of visual localization decreased when subjects were exposed to inertial forces.
      Moreover, subjects localized the memorized visual targets more to the right than
      their actual position, that was in the direction of the inertial forces. With
      further analysis, it appeared that this shift of localization was concomitant
      with a shift of the visual straight ahead (VSA) in the opposite direction. Thus,
      the modified gravitoinertial force field led to a modification in the orientation
      of the egocentric reference frame. Furthermore, this shift of localization
      increased when the head was free to move while the head was tilted in roll toward
      the center of rotation of the platform and turned in yaw in the same direction.
      It is concluded that the orientation of the egocentric reference frame was
      influenced by the gravitoinertial vector.

PMID- 15578171
TI  - Distinct changes in cortical and spinal excitability following high-frequency
      repetitive TMS to the human motor cortex.
AB  - It has been shown that high-frequency repetitive transcranial magnetic
      stimulation (rTMS) to the human primary motor hand area (M1-HAND) can induce a
      lasting increase in corticospinal excitability. Here we recorded motor evoked
      potentials (MEPs) from the right first dorsal interosseus muscle to investigate
      how sub-threshold high-frequency rTMS to the M1-HAND modulates cortical and
      spinal excitability. In a first experiment, we gave 1500 stimuli of 5 Hz rTMS. At
      an intensity of 90% of active motor threshold, rTMS produced no effect on MEP
      amplitude at rest. Increasing the intensity to 90% of resting motor threshold
      (RMT), rTMS produced an increase in MEP amplitude. This facilitatory effect
      gradually built up during the course of rTMS, reaching significance after the
      administration of 900 stimuli. In a second experiment, MEPs were elicited during
      tonic contraction using weak anodal electrical or magnetic test stimuli. 1500
      (but not 600) conditioning stimuli at 90% of RMT induced a facilitation of MEPs
      in the contracting FDI muscle. In a third experiment, 600 conditioning stimuli
      were given at 90% of RMT to the M1-HAND. Using two well-established conditioning
      test paradigms, we found a decrease in short-latency intracortical inhibition
      (SICI), and a facilitation of the first peak of facilitatory I-waves interaction
      (SICF). There was no correlation between the relative changes in SICI and SICF.
      These results demonstrate that subthreshold 5 Hz rTMS can induce lasting changes
      in specific neuronal subpopulations in the human corticospinal motor system,
      depending on the intensity and duration of rTMS. Short 5 Hz rTMS (600 stimuli) at
      90% of RMT can selectively shape the excitability of distinct intracortical
      circuits, whereas prolonged 5 Hz rTMS (> or =900 stimuli) provokes an overall
      increase in excitability of the corticospinal output system, including spinal
      motoneurones.

PMID- 15578172
TI  - A pharmacokinetic study comparing single and repeated oral doses of 20 mg and 40
      mg omeprazole and its two optical isomers, S-omeprazole (esomeprazole) and R
      omeprazole, in healthy subjects.
AB  - OBJECTIVE: To investigate the pharmacokinetics of S-omeprazole (esomeprazole), R
      omeprazole and racemic omeprazole following single and repeated oral doses of 20
      mg and 40 mg of each compound in healthy male and female subjects. METHODS: In an
      open, randomised, three-way, cross-over study, 12 subjects received 20 mg and
      another 12 subjects received 40 mg S-omeprazole, R-omeprazole and racemic
      omeprazole as oral solutions once daily for 5 days, separated by washout periods
      of at least 10 days. Blood samples were taken for analysis pre-dose and at
      selected time points during a 12-h period following drug administration on study
      day 1 and day 5. Pharmacokinetic parameters of S-omeprazole, R-omeprazole,
      racemic omeprazole and the two main metabolites (5-hydroxy and sulphone) were
      calculated using non-compartmental analysis. RESULTS: Following the 20-mg dose of
      each compound, values of the total area under the plasma concentration-time curve
      (AUC) were 1.52, 0.62 and 1.04 micromol h/l for S-omeprazole, R-omeprazole and
      racemic omeprazole, respectively, on day 1. Respectively, AUC values on day 5
      were 2.84, 0.68 and 1.63 micromol h/l. Corresponding values after the 40-mg doses
      were 3.88, 1.39 and 2.44 micromol h/l on day 1 and 9.32, 1.80 and 5.79 micromol
      h/l on day 5. CONCLUSION: Treatment with S-omeprazole (esomeprazole; 20 mg and 40
      mg) resulted in higher AUC values than with either R-omeprazole or racemic
      omeprazole after both single and repeated doses due to a lower metabolic rate of
      S-omeprazole than R-omeprazole and, consequently, racemic omeprazole. S
      Omeprazole, R-omeprazole and the racemate were well tolerated.

PMID- 15578173
TI  - Structure and markers of appropriateness, quality and performance of drug
      treatment over a 1-year period after hospital discharge in a cohort of elderly
      patients with cardiovascular diseases from Germany.
AB  - In a group of elderly patients over 65 years of age with at least two
      cardiovascular diagnoses requiring chronic medication (n=424), drug therapy at
      hospital discharge and at home thereafter was followed for a 1-year period. Two
      home visits took place at 3 months and 12 months after initial discharge. A
      median of six prescriptions had already been given at the time of discharge; this
      number increased slightly during ambulatory follow-up. After 1 year, about 30% of
      the patients had to take more than ten dosing units per day. After discharge,
      about 50% of all prescriptions were subject to changes in the choice of the
      preparation (brand-generic) or the agent used [within a class of similar agents,
      e.g. angiotensin converting enzyme inhibitors (ACIs)]. The prescription of some
      problematic agents (benzodiazepines, non-steroidal anti-inflammatory agents)
      increased during the ambulatory follow-up, but pivotal medications for
      cardiovascular indications (e.g., ACI) given at discharge were maintained. Over
      the-counter (OTC) drugs-which were not part of the discharge medication
      contributed to 12% of all drugs taken at V4. The majority of the prescriptions
      (95% of about 2,000 prescriptions surveyed at each visit) was in agreement with
      the drug's approval status and was appropriate in terms of absence of
      contraindications. At home visits, therapy with ACI or beta-blocking agents was
      in agreement with clinical guidelines, although under-dosing was obvious. Blood
      pressure control (<140/90 mmHg) was achieved in 61% of the patients at discharge
      and deteriorated to 45% after 1 year; international normalized ratio control in
      patients with oral anticoagulation also declined (control rate 57% at discharge,
      46% after 1 year). Statins as secondary prevention were given at discharge in
      only 60% of suitable patients, declining to about 50% in ambulatory visits.
      Diabetic control was not present in 35% of the patients at discharge or at home.
      Properties of or reason for their medication could be given for the majority (70
      80%) of the prescriptions; these quotations were, however, cursory and almost
      nothing was known about medication risks. At home visits, non-compliance was
      admitted for approximately 8% of the prescriptions. In conclusion, for pivotal
      indications, family doctors widely followed the discharge recommendations, but
      deficits in ambulatory prescriptions and poor performance of the medication were
      in part already employed at the time of discharge from the hospital. The lack of
      a patient's knowledge about their own medication is precarious.

PMID- 15578174
TI  - Considerable haplotypic diversity in the RT1-CE class I gene region of the rat
      major histocompatibility complex.
AB  - The major histocompatibility complex (MHC) class I region extending between the
      Bat1 and Pou5f1 genes shows considerable genomic plasticity in mouse and rhesus
      macaque but not in human haplotypes. In the rat, this region is known as the RT1
      CE region. The recently published rat MHC sequence gave rise to a complete set of
      class I gene sequences in a single MHC haplotype, namely the RT1(n) haplotype of
      the widely used BN inbred strain. To study the degree of genetic diversity, we
      compared the RT1-CE region-derived class I genes of the RT1(n) haplotype with
      class I sequences of other rat haplotypes. By using phylogenetic tree analyses,
      we obtained evidence for extensive "presence and absence" polymorphisms of single
      loci and even small subfamilies of class I genes in the rat. Alleles of RT1-CE
      region class I genes could also be identified, but the rate of allelic nucleotide
      substitutions appeared rather low, indicating that the diversity in the RT1-CE
      region is mainly based on genomic plasticity.

PMID- 15578175
TI  - Identification and sequence analysis of chicken Toll-like receptors.
AB  - Toll-like receptors (TLRs) play an important role in the recognition of microbial
      components. Only chicken TLR2 and -4 have been reported in the literature. The
      objectives of this study were to identify new chicken TLRs and to evaluate
      evolutionary significance of these receptors. Searching chicken genomic databases
      and DNA sequencing revealed five new TLRs, TLR1 (type 1 and 2), -3, -5, and -7.
      No chicken orthologues of mammalian TLR8, -9, or -10 were found. As in mammals,
      all chicken TLRs (chTLRs) share identical protein secondary structure that
      consists of several leucine-rich domains, a transmembrane domain, and
      Toll/Interleukin-1 receptor domain(s). Phylogenetic analyses indicate that the
      identified chTLR genes are the orthologues of TLRs in mammals. Analyses of the
      number of synonymous substitutions per synonymous site and nonsynonymous
      substitutions per nonsynonymous site indicate that the nucleotide sequences
      coding for the leucine-rich repeats of chicken TLR1 type 1 and type 2 were
      significantly under positive Darwinian selection. In contrast, the sequences of
      other TLRs were under purifying selection. These results support the hypothesis
      that one of the major evolutionary strategies of the innate immune system is to
      recognize a few highly conserved microbial components with several conserved
      TLRs. The results also indicate that the sequence changes in the ligand-binding
      domains of TLR1 in chickens provide adaptive advantages during evolution.

PMID- 15578176
TI  - Characterization of two genes encoding leucine-rich repeat-containing proteins in
      grass carp Ctenopharyngodon idellus.
AB  - The cDNAs and genes of two different types of leucine-rich repeat-containing
      proteins from grass carp (Ctenopharyngodon idellus) were cloned. Homology search
      revealed that the two genes, designated as GC-GARP and GC-LRG, have 37% and 32%
      deduced amino-acid sequence similarities with human glycoprotein A repetitions
      predominant precursor (GARP) and leucine-rich alpha2-glycoprotein (LRG),
      respectively. The cDNAs of GC-GARP and GC-LRG encoded 664 and 339 amino acid
      residues, respectively. GC-GARP and GC-LRG contain many distinct structural
      and/or functional motifs of the leucine-rich repeat (LRR) subfamily, such as
      multiple conserved 11-residue segments with the consensus sequence LxxLxLxxN/CxL
      (x can be any amino acid). The genes GC-GARP and GC-LRG consist of two exons,
      with 4,782 bp and 2,119 bp in total length, respectively. The first exon of each
      gene contains a small 5'-untranslated region and partial open reading frame. The
      putative promoter region of GC-GARP was found to contain transcription factor
      binding sites for GATA-1, IRF4, Oct-1, IRF-7, IRF-1, AP1, GATA-box and NFAT, and
      the promoter region of GC-LRG for MYC-MAX, MEIS1, ISRE, IK3, HOXA9 and C/EBP
      alpha. Phylogenetic analysis showed that GC-GARP and mammalian GARPs were
      clustered into one branch, while GC-LRG and mammalian LRGs were in another
      branch. The GC-GARP gene was only detected in head kidney, and GC-LRG in the
      liver, spleen and heart in the copepod (Sinergasilus major)-infected grass carp,
      indicating the induction of gene expression by the parasite infection. The
      results obtained in the present study provide insight into the structure of fish
      LRR genes, and further study should be carried out to understand the importance
      of LRR proteins in host-pathogen interactions.

PMID- 15578177
TI  - Bioactive berry compounds-novel tools against human pathogens.
AB  - Berry fruits are rich sources of bioactive compounds, such as phenolics and
      organic acids, which have antimicrobial activities against human pathogens. Among
      different berries and berry phenolics, cranberry, cloudberry, raspberry,
      strawberry and bilberry especially possess clear antimicrobial effects against,
      e.g. Salmonella and Staphylococcus. Complex phenolic polymers, like
      ellagitannins, are strong antibacterial agents present in cloudberry and
      raspberry. Several mechanisms of action in the growth inhibition of bacteria are
      involved, such as destabilisation of cytoplasmic membrane, permeabilisation of
      plasma membrane, inhibition of extracellular microbial enzymes, direct actions on
      microbial metabolism and deprivation of the substrates required for microbial
      growth. Antimicrobial activity of berries may also be related to antiadherence of
      bacteria to epithelial cells, which is a prerequisite for colonisation and
      infection of many pathogens. Antimicrobial berry compounds may have important
      applications in the future as natural antimicrobial agents for food industry as
      well as for medicine. Some of the novel approaches are discussed.

PMID- 15578178
TI  - Gibberellin biosynthesis in fungi: genes, enzymes, evolution, and impact on
      biotechnology.
AB  - Gibberellins (GAs) constitute a large family of tetracyclic diterpenoid
      carboxylic acids, some members of which function as growth hormones in higher
      plants. As well as being phytohormones, GAs are also present in some fungi and
      bacteria. In recent years, GA biosynthetic genes from Fusarium fujikuroi and
      Arabidopsis thaliana have been cloned and well characterised. Although higher
      plants and the fungus both produce structurally identical GAs, there are
      important differences indicating that GA biosynthetic pathways have evolved
      independently in higher plants and fungi. The fact that horizontal gene transfer
      of GA genes from the plant to the fungus can be excluded, and that GA genes are
      obviously missing in closely related Fusarium species, raises the question of the
      origin of fungal GA biosynthetic genes. Besides characterisation of F. fujikuroi
      GA pathway genes, much progress has been made in the molecular analysis of
      regulatory mechanisms, especially the nitrogen metabolite repression controlling
      fungal GA biosynthesis. Basic research in this field has been shown to have an
      impact on biotechnology. Cloning of genes, construction of knock-out mutants,
      gene amplification, and regulation studies at the molecular level are powerful
      tools for improvement of production strains. Besides increased yields of the
      final product, GA3, it is now possible to produce intermediates of the GA
      biosynthetic pathway, such as ent-kaurene, ent-kaurenoic acid, and GA14, in high
      amounts using different knock-out mutants. This review concentrates mainly on the
      fungal biosynthetic pathway, the genes and enzymes involved, the regulation
      network, the biotechnological relevance of recent studies, and on evolutionary
      aspects of GA biosynthetic genes.

PMID- 15578179
TI  - Strategies and perspectives for genetic improvement of wine yeasts.
AB  - Recent developments in expression profile and proteomic techniques illustrated
      that the main oenological traits of wine yeasts are complex and influenced by
      several genes, each of them identified as absolutely essential. Only for
      monogenic properties the genetic improvement programmes of wine yeasts can be
      performed by alteration of individual genes. Ideally the most productive way of
      improving the whole-cell biocatalysts is by evolution of the entire cell genome.
      In this article we briefly review the main genetic improvement techniques applied
      in new and optimised wine strains construction, paying particular attention to
      blind and whole genome strategies, such as the sexual recombination and genome
      shuffling.

PMID- 15578180
TI  - Methyl jasmonate elicitation enhanced synthesis of ginsenoside by cell suspension
      cultures of Panax ginseng in 5-l balloon type bubble bioreactors.
AB  - The effects of methyl jasmonate (MJ) elicitation on the cell growth and
      accumulation of ginsenoside in 5-l bioreactor suspension cultures of Panax
      ginseng were investigated. Ginsenoside accumulation was enhanced by elicitation
      by MJ (in the range 50-400 microM); however, fresh weight, dry weight and growth
      ratio of the cells was strongly inhibited by increasing MJ concentration. The
      highest ginsenoside yield was obtained at 200 microM MJ. In the second
      experiment, 200 microM MJ was added on day 15 during the cultivation. The
      ginsenoside, Rb group, and Rg group ginsenoside content increased 2.9, 3.7, and
      1.6 times, respectively, after 8 days of MJ treatment. Rb group gisnsenosides
      accumulated more than Rg group ginsenosides. Among Rb group ginsenosides, Rb1
      content increased significantly by four times but the contents of Rb2, Rc and Rd
      increased only slightly. Among Rg group ginsenosides, Rg1 and Re showed 2.3-fold
      and 3.0-fold increments, respectively, whereas there was only a slight increment
      in Rf group ginsenosides. These results suggest that MJ elicitation is beneficial
      for ginsenoside production using 5-l bioreactor cell suspension cultures.

PMID- 15578181
TI  - Bacillus subtilis M4 decreases plant susceptibility towards fungal pathogens by
      increasing host resistance associated with differential gene expression.
AB  - Results presented in this paper describe the ability of Bacillus subtilis strain
      M4 to reduce disease incidence caused by Colletotrichum lagenarium and Pythium
      aphanidermatum on cucumber and tomato, respectively. Disease protection in both
      pathosystems was most probably due to induction of resistance in the host plant
      since experiments were designed in order to avoid any direct contact between the
      biocontrol agent and the pathogen. Pre-inoculation with strain M4 thus sensitised
      both plants to react more efficiently to subsequent pathogen infection. In
      cucumber, the use of endospores provided a disease control level similar to that
      obtained with vegetative cells. In contrast, a mixture of lipopeptides from the
      surfactin, iturin and fengycin families showed no resistance-inducing potential.
      Interestingly, treatment with strain M4 was also associated with significant
      changes in gene transcription in the host plant as revealed by cDNA-AFLP
      analyses. Several AFLP fragments corresponded to genes not expressed in control
      plants and specifically induced by the Bacillus treatment. In support to the
      macroscopic protective effect, this differential accumulation of mRNA also
      illustrates the plant reaction following perception of strain M4, and constitutes
      one of the very first examples of defence-associated modifications at the
      transcriptional level elicited by a non-pathogenic bacterium in a host plant.

PMID- 15578182
TI  - Cancer and aging: symposium of the 27th annual meeting of the Japanese society
      for biomedical gerontology, Tokyo.
AB  - Although many hypotheses have been proposed to explain the strong link between
      aging and cancer, the exact mechanisms responsible for the increased frequency of
      occurrence of cancer with advancing age have not been fully defined. Recent
      evidence indicates that malregulation of the apoptotic process may be involved in
      some aging process as well as in the development of cancer. Although it is still
      under debate how apoptosis is expressed during aging in vivo, this phenomenon is
      an important factor in unwinding the complicated mechanisms that link cancer and
      aging. In this review, we report on the discussion at the symposium of the 27th
      annual meeting of the Japanese society for biomedical gerontology, regarding
      recent findings from aging and carcinogenesis studies using animal models, the
      characteristics of cancer in patients with Werner's syndrome, the epigenetic
      changes in human cancers and aging, and the characteristics of human cancers in
      the elderly. It was concluded that apoptosis plays a role in the aging process
      and carcinogenesis in vivo, likely as an inherent protective mechanism against
      various kinds of damages to genes/chromosomes.

PMID- 15578183
TI  - Assessment of image quality of a standard and three dose-reducing protocols in
      adult cranial CT.
AB  - The purpose of this study was to analyze the effect of various tube current
      settings (mAs) and optimize the image quality and dose for adult cranial CT
      protocol. Sixty adult patients who underwent a cranial CT scanning for different
      indications were subdivided into three subgroups. Subjective image and noise
      quality scores and quantitative noise measurements were selectively studied on
      three reference levels (cerebellar, basal ganglia and centrum semiovale levels).
      For each subgroup, only one level was studied. Head circumference (HC) and the
      maximum anteroposterior diameter (MAPD) of each patient were measured. At 50%
      decreased dose protocol, there was no poor quality score at any level. At nearly
      60% decreased dose protocol, the incidence of poor quality scores was much higher
      at the cerebellar level than at the other two levels. For the same protocol
      number, quantitative noise measurements were higher at the cerebellar level than
      the other two supratentorial levels. The correlation was found to be significant
      between HC, MAPD and quantitative noise measurements, and there was a non
      significant correlation between HC and subjective noise scores. In adult cranial
      CT, depending on the level, a dose reduction of up to 60% may be possible while
      maintaining image quality.

PMID- 15578184
TI  - Computer-assisted detection of pulmonary nodules: evaluation of diagnostic
      performance using an expert knowledge-based detection system with variable
      reconstruction slice thickness settings.
AB  - The purpose of this study was to evaluate the performance of a computer-assisted
      diagnostic (CAD) tool using various reconstruction slice thicknesses (RST). Image
      data of 20 patients undergoing multislice CT for pulmonary metastasis were
      reconstructed at 4.0, 2.0 and 0.75 mm RST and assessed by two blinded
      radiologists (R1 and R2) and CAD. Data were compared against an independent
      reference standard. Nodule subgroups (diameter >10, 4-10, <4 mm) were assessed
      separately. Statistical methods were the ROC analysis and Mann-Whitney U test.
      CAD was outperformed by readers at 4.0 mm (Az = 0.18, 0.62 and 0.69 for CAD, R1
      and R2, respectively; P<0.05), comparable at 2.0 mm (Az = 0.57, 0.70 and 0.69 for
      CAD, R1 and R2, respectively), and superior using 0.75 mm RST (Az = 0.80, 0.70
      and 0.70 and sensitivity = 0.74, 0.53 and 0.53 for CAD, R1 and R2, respectively;
      P<0.05). Reader performances were significantly enhanced by CAD (Az = 0.93 and
      0.95 for R1 + CAD and R2 + CAD, respectively, P<0.05). The CAD advantage was best
      for nodules <10 mm (detection rates = 93.3, 89.9, 47.9 and 47.9% for R1 + CAD, R2
      + CAD, R1 and R2, respectively). CAD using 0.75 mm RST outperformed radiologists
      in nodules below 10 mm in diameter and should be used to replace a second
      radiologist. CAD is not recommended for 4.0 mm RST.

PMID- 15578185
TI  - Urological views and perspectives.

PMID- 15578186
TI  - [LASEK: results after 1 year. Retrospective analysis based on the dioptric power
      matrix for moderate myopic and astigmatic correction].
AB  - PURPOSE: The aim of this study was to assess astigmatism magnitude and axis
      changes based on the dioptric power matrix in low to moderate levels of myopia
      and astigmatism treated with LASEK. PATIENTS AND METHODS: This retrospective
      analysis included 54 myopic eyes treated with LASEK with a minimum follow-up of
      12 months. An epithelial flap was created by 25-45 s of 20% alcohol exposure. The
      corneal surface was ablated using two different excimer lasers and nomogram
      adjustment. The flap was repositioned and a bandage applied to the contact lens.
      Main outcome measures were manifest refraction as calculated with the dioptric
      power matrix, UCVA, BSVCA, and retreatment rate. RESULTS: Mean manifest
      refraction is shown in table 2 (Tabelle 2). UCVAs of 20/20 or better were found
      in 33% of eyes at 1 week and in more than 53% at 3 months to 1 year. The safety
      index remained > or =0.98 after postoperative week 4. The efficacy index varied
      between 0.91 and 0.98 after 1 month. CONCLUSION: LASEK for correction of low to
      moderate myopia and astigmatism seems to be a safe, effective, and stable option.

PMID- 15578187
TI  - The action of spike frequency adaptation in the postural motoneurons of hermit
      crab abdomen during the first phase of reflex activation.
AB  - Cuticular strain associated with support of the shell of the hermit crab, Pagurus
      pollicarus, by its abdomen activates mechanoreceptors that evoke a stereotyped
      reflex in postural motoneurons. This reflex consists of three phases: a brief
      high-frequency burst of motoneuron spikes, a pause, and a much longer duration
      but lower frequency period of spiking. These phases are correlated with a rapid
      increase in muscle force followed by a slight decline to a level of tone that is
      greater than that at rest but less than maximal. The present experiments address
      the mechanisms underlying the transition from the first to second phase of the
      reflex and their role in force generation. Although centrally generated
      inhibitory post-synaptic potentials (IPSPS) are present during the pause period
      of the reflex, intracellular current injection of motoneurons reveals a spike
      frequency adaptation that rapidly and substantially reduces motoneuron firing
      frequency and is unchanged in saline that reduces synaptic transmission. The
      adaptation is voltage sensitive and persists for several hundred milliseconds
      upon repolarization. Hyperpolarization partially restores the initial response of
      the motoneuron to depolarizing current. Spike frequency adaptation and synaptic
      inhibition are important mechanisms in the generation of force that maintains
      abdominal stiffness at a constant, submaximal level.

PMID- 15578188
TI  - Diel variation in ammonia excretion, glutamine levels, and hydration status in
      two species of terrestrial isopods.
AB  - Terrestrial isopods (suborder Oniscidea) excrete most nitrogen diurnally as
      volatile ammonia, and ammonia-loaded animals accumulate nonessential amino acids,
      which may constitute the major nocturnal nitrogen pool. This study explored the
      relationship between ammonia excretion, glutamine storage/mobilization, and water
      balance, in two sympatric species Ligidium lapetum (section Diplocheta), a hygric
      species; and Armadillidium vulgare (Section Crinocheta), a xeric species capable
      of water-vapor absorption (WVA). Ammonia excretion (12-h), tissue glutamine
      levels, and water contents were measured following field collection of animals at
      dusk and dawn. In both species, diurnal ammonia excretion exceeded nocturnal
      excretion four- to fivefold while glutamine levels increased four- to sevenfold
      during the night. Most glutamine was accumulated in the somatic tissues ("body
      wall"). While data support the role of glutamine in nocturnal nitrogen storage,
      potential nitrogen mobilization from glutamine breakdown (162 micromol g(-1) in
      A. vulgare) exceeds measured ammonia excretion (2.5 micromol g(-1)) over 60-fold.
      This may serve to generate the high hemolymph ammonia concentrations (and high
      P(NH3)) seen during volatilization. The energetic cost of ammonia volatilization
      is discussed in the light of these findings. Mean water contents were similar at
      dusk and dawn in both species, indicating that diel cycles of water depletion and
      replenishment were not occurring.

PMID- 15578189
TI  - Pyloric duplication in a neonate: a rare entity.
AB  - Duplications of the alimentary tract are rare anomalies that have been reported
      to occur all along the gastrointestinal tract. Of the various alimentary tract
      duplications, pyloric duplications are extremely rare. We report the case of a 3
      day-old neonate who was antenatally diagnosed as having a cystic mass in the
      abdomen and who presented with vomiting on the 2nd day of life. At operation, a
      duplication cyst of the pylorus was removed successfully and a pyloroantrectomy
      performed.

PMID- 15578190
TI  - Bilateral megaureters in the Adriamycin rat model.
AB  - Congenital obstructive uropathy is associated with significant morbidity and
      mortality in the human neonate. The pathophysiology of congenital obstructive
      uropathy is poorly understood. There are very few experimental models of prenatal
      obstruction of the urinary tract, except in the fetal lamb or inbred rats.
      Prenatal exposure to Adriamycin in a rat model leads to a spectrum of
      malformations including urinary tract anomalies. We hypothesized that Adriamycin
      administration during a particular time frame could yield a high incidence of
      urinary tract anomalies and therefore designed this study to investigate the
      rates of urinary tract anomalies at different windows of Adriamycin injection in
      rat embryos. Adriamycin (1.75 mg/kg) was administered intraperitoneally to
      pregnant rats at different times from days 6 to 10 of gestation. Control animals
      were given saline. Embryos recovered on gestational day 21 by cesarean section
      were examined for urinary tract anomalies, and malformations were noted. Sections
      were then processed for paraffin embedding, sectioned at 5 mum, and stained with
      hematoxylin and eosin for histological examination. Anomalies of the urinary
      tract occurred maximally following Adriamycin administration on days 7, 8, and 9
      of gestation (91.6%) compared with 16% of controls. The most common urinary tract
      anomaly in the Adriamycin group was bilateral megaureters with a hypoplastic
      bladder (81%). Other anomalies included unilateral or bilateral
      ureterohydronephrosis with a normal-sized bladder, duplex kidney, and unilateral
      or bilateral renal agenesis. In conclusion, the critical embryologic window for
      the development of bilateral megaureters with a small bladder in the Adriamycin
      rat model occurs following Adriamycin administration on gestational days 7-9.
      This simple experimental model of bilateral megaureter may allow further research
      into the pathophysiology of this condition.

PMID- 15578191
TI  - Impaired mucosal regeneration in neonatal necrotising enterocolitis.
AB  - Necrotising enterocolitis (NEC) remains an overwhelming gastrointestinal (GI)
      emergency in premature infants, with an annual incidence of 350 cases and a
      mortality of 23% in the United Kingdom. The aetiology of NEC is multifactorial
      and its pathogenesis poorly understood. It is characterised by severe necrotic
      damage to the intestine. Mucus is an adherent, viscoelastic gel layer protecting
      the delicate underlying epithelium from lumenal aggressors such as digestive
      enzymes and bacterial toxins. The group of trefoil factor peptides (TFF1-3) are
      part of the protective mechanism operating in the intestinal mucosa and play a
      fundamental role in epithelial protection, repair, and restitution. These
      secreted peptides have been identified in a site-specific pattern in the GI
      mucosa, and their expression has been shown to be upregulated in early stages of
      mucosal repair. The role of trefoil peptides in neonatal mucosal protection has
      not been well investigated. Impaired mucosal regeneration due in part to failure
      of upregulation of TFF expression may contribute to the pathogenesis of NEC. The
      aim of this study was to investigate TFF1-3 mRNA expression and to identify the
      gene product in the GI tracts of normal neonatal controls and infants with NEC.
      Parents of all babies having a laparotomy in the neonatal period (defined as up
      to 44 weeks' gestation) and bowel resection were approached for written consent.
      Bowel samples were fixed in formalin and then embedded in paraffin in an RNAse
      free manner. In situ hybridisation and immunohistochemistry were performed to
      examine the pattern of trefoil mRNA expression and to localise the peptides in
      the neonatal GI tract. Forty neonatal bowel specimens were examined. Twelve
      patients had NEC, eight were recovering from NEC, and 20 control specimens were
      obtained. TFF1 and TFF2 mRNA expression were not detected in the majority of NEC
      specimens, and there was a relative downregulation of TFF3 expression in 83% of
      NEC patients. TFF1 and TFF2 expression were noted in the recovery phase from NEC.
      Immunohistochemistry revealed a decrease in TFF3 gene product in sites adjacent
      to mucosal damage secondary to NEC. In acute NEC there was no apparent expression
      of TFF1 and 2 protein. In the group of patients recovering from NEC, TFF1 and 2
      expression were seen in association with regenerative changes in the mucosa.
      Previous data has shown TFF1-3 to be upregulated in the acute phase response to
      mucosal injury in the gut. Trefoil peptides have been shown to promote epithelial
      cell migration and protect against apoptosis. Our results suggest that there is a
      lack of TFF expression in response to NEC in the premature gut. This may lead to
      impaired restitution of the mucosa and contribute to the cascade of bowel
      necrosis and generalised sepsis characteristic of NEC.

PMID- 15578192
TI  - Altered expression of angiotensin II receptor subtypes and transforming growth
      factor-beta in the heart of nitrofen-induced diaphragmatic hernia in rats.
AB  - The renin-angitensin system (RAS) plays an important role as a growth factor in
      cardiac development. Angiotensin converting enzyme is involved in converting
      angiotensin I to angiotensin II (Ag-II). The effects of Ag-II are mediated by two
      primary receptors, type 1 (AT1) and type 2 (AT2). Ag-II stimulates transforming
      growth factor-beta1(TGF-beta1) and acts as a potent stimulant of myocyte growth
      and fetal contractile protein gene transcription. The aim of this study was to
      determine the expression of Ag-II receptor subtypes and TGF-beta1 in the
      hypoplastic heart of nitrofen-induced congenital diaphragmatic hernia (CDH). CDH
      was induced in pregnant rats following administration of 100 mg nitrofen on day
      9.5. The fetuses were divided into three groups: normal controls (n=16), nitrofen
      treated without CDH (n=16), and nitrofen-induced CDH (n=16). Reverse
      transcriptase-polymerase chain reaction was performed to evaluate mRNA expression
      of AT1, AT2, and TGF-beta1. Levels of mRNA were expressed as a ratio of the band
      density divided by that of beta-actin. AT1 and AT2 mRNA expressions were
      significantly decreased in CDH heart compared with controls (0.43+/-0.33 vs.
      1.0+/-0.48 and 0.62+/-0.23 vs. 1.4+/-0.43, respectively). TGF-beta1 mRNA
      expressions were also significantly decreased in CDH heart compared with controls
      (0.38+/-0.17 vs. 0.72+/-0.26). No significant difference was found between the
      hearts of controls and nitrofen-treated rats without CDH. The decreased
      expression of AT1, AT2, and TGF-beta1 mRNA in the hypoplastic heart suggests that
      the downregulation of RAS may be involved in the pathogenesis of cardiac
      hypoplasia in nitrofen-induced CDH.

PMID- 15578193
TI  - Foregut mesenchyme contributes cells to pancreatic acini during embryonic
      development in a chick-quail chimera model.
AB  - To understand causes of developmental abnormalities of the pancreas, it is
      essential to understand its normal embryonic development. Current understanding
      of the development of pancreatic exocrine tissue is that it develops solely from
      embryonic epithelium, while the role of the surrounding mesenchyme is to signal
      to this epithelium and form connective tissue. Recent work in our laboratory has
      shown that pancreatic bud mesenchyme can contribute cells to islets during
      embryonic development. However, no published studies have investigated in detail
      whether mesenchyme contributes cells to the exocrine structures of the pancreas.
      The aim of this study was to investigate whether cells from foregut mesenchyme
      can contribute to pancreatic acini during embryonic development. Chick-quail
      chimera recombinant organs were constructed using pancreatic epithelium and
      mesenchyme from either the pancreas (n=12) or stomach (n=25). These were cultured
      for 7 days in 3-D collagen gels. The resulting specimens were analysed using
      morphological criteria and fluorescent immunocytochemistry against pancreatic
      amylase, insulin, and the quail-specific nucleolar antigen QCPN. Two independent
      observers determined the origins of acini as either solely epithelial, solely
      mesenchymal, or of mixed origin. Results are expressed as percentages of total
      acini identified in each group. Statistical analysis was performed using chi(2)
      tests (P<0.01 was considered statistically significant). Recombinations of
      pancreatic epithelium and pancreatic mesenchyme yielded 11 acini, of which 45%
      were derived from epithelium only, 45% from mesenchyme only, and 10% of mixed
      origin. Recombinations of pancreatic epithelium and stomach mesenchyme yielded 78
      acini, of which 40% were derived from epithelium only, 32% from mesenchyme only,
      and 28% of mixed origin. When acini with any mesenchymal cellular contribution
      were considered as a group, there was no significant difference between stomach
      and pancreatic mesenchymal contribution (P=0.72). This is the first study to
      demonstrate the cellular contribution of mesenchyme to pancreatic exocrine
      structures. Our data show that mesenchyme contributes cells to pancreatic acini
      during development in this model and that mesenchyme derived from stomach and
      pancreatic sources are both able to form acini.

PMID- 15578194
TI  - Association of Crohn's disease and latent celiac disease: a case report and
      review of the literature.
AB  - BACKGROUND: Crohn's disease is a chronic inflammatory disease of the intestine
      potentially affecting all parts of the intestine with predilection sites in the
      terminal ileum and proximal colon. Its prevalence in Western Europe is 20
      40/100,000 with equal affection of both sexes and familiar accumulation.
      Histopathologically, it is characterized by a discontinuous, segmental
      manifestation and implication of all intestinal layers. Celiac disease, on the
      other hand, is defined by histologically proven villous atrophy associated with
      hyperplasia of crypts, lymphocytic infiltration and clinical improvement after a
      gluten-free diet. CASE REPORT: We report the case of a 52-year-old man presenting
      with long-term diarrhea and loss of weight associated with Crohn's disease. After
      interventional therapy for an unstable coronary artery syndrome and medical
      therapy for hyperthyroidism, the diarrhea stopped only after maintaining a gluten
      free diet. A latent form of celiac disease (clinical symptoms, improvement after
      gluten-free diet, detection of anti-gliadin IgA antibodies, negative histology)
      was diagnosed. CONCLUSION: To our knowledge, this is the first report on the
      association of Crohn's disease and the latent form of celiac disease in the same
      patient. Whereas in most cases, Crohn's disease develops secondary to a pre
      existing celiac disease, in our patient, latent celiac disease was diagnosed
      years after the onset of and therapy for Crohn's disease.

PMID- 15578195
TI  - Probiotic bacteria stimulate virus-specific neutralizing antibodies following a
      booster polio vaccination.
AB  - BACKGROUND: Orally ingested probiotic bacteria may modulate the immune response
      and increase antibody titers against enteric infections by bacteria or viruses.
      Even though positive effects of probiotics on respiratory tract infections have
      been reported, overall only few studies have examined effects on virus infections
      concerning organs other than the gastrointestinal tract. AIM OF THE STUDY: It was
      the aim of the study to investigate whether and how probiotics affect the immune
      response to a standardized enterovirus challenge (polio) and infections not
      limited to the gastrointestinal tract in healthy adults. METHODS: In a
      randomized, controlled and double-blind study 64 volunteers consumed for 5 weeks
      chemically acidified clotted milk without bacteria or with 10(10)/serving
      (Lactobacillus rhamnosus ) GG or Lactobacillus acidophilus CRL431 added. In the
      second week subjects were vaccinated orally against polio 1, 2 and 3. Polio virus
      neutralizing serum activity, the primary parameter, was determined by the
      standard neutralization test (WHO) before and three times after vaccination.
      Polio-specific IgA, IgG and IgM were detected by ELISAs. RESULTS: Probiotics
      increased poliovirus neutralizing antibody titers (NT) and affected the formation
      of poliovirus-specific IgA and IgG in serum. The maximum increase after
      immunization was about 2, 2.2, or 4-fold higher, respectively, for NT, IgG or,
      IgA, in volunteers consuming probiotics instead of placebo. No consistent
      difference was noted between bacterial strains. CONCLUSIONS: Probiotics induce an
      immunologic response that may provide enhanced systemic protection of cells from
      virus infections by increasing production of virus neutralizing antibodies.

PMID- 15578196
TI  - Endothelial nitric oxide synthase gene transfer restores endothelium-dependent
      relaxations and attenuates lesion formation in carotid arteries in apolipoprotein
      E-deficient mice.
AB  - Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly
      opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles
      including vasodilation and inhibition of platelet aggregation, smooth muscle cell
      proliferation, and endothelial monocyte adhesion, the last effect being mediated
      by MCP-1 downregulation. Early stages of arteriosclerosis are associated with
      reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated
      adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of
      a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1
      inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE(-/-)) mice.
      Endothelium-dependent relaxations were impaired in carotid arteries instilled
      with a noncoding adenoviral vector but were restored by eNOS gene transfer (p <
      0.01). A perivascular collar was placed around the common carotid artery to
      accelerate lesion formation. eNOS gene transfer reduced lesion surface areas,
      intima/media ratios, and macrophage contents in the media at 5-week follow-up (p
      < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation.
      In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and
      inhibits lesion formation in ApoE(-/-) mouse carotids. Further studies are needed
      to assess whether vasoprotection is maintained at later disease stages and to
      evaluate the long-term efficacy of eNOS gene therapy for primary
      arteriosclerosis.

PMID- 15578197
TI  - Suffocation and poisoning--the hard-hitting side of Munchausen syndrome by proxy.
AB  - Munchausen syndrome by proxy (MSBP) is a severe and difficult to diagnose form of
      child abuse characterised by the simulation, aggravation or production of
      symptoms of illness in a child by an adult. MSBP often leads to multiple
      hospitalisations and has a high mortality and long-term morbidity. This study
      describes the cases of 5 families with 8 children affected who presented with
      unexplained neurological or gastrointestinal symptoms or even loss of
      consciousness. All were victims of poisoning or suffocation by their mothers. Two
      of those children died and were initially diagnosed as SIDS or natural death,
      respectively. They were only recognised as MSBP victims after another sibling had
      fallen ill with similar symptoms. The cases are discussed in consideration of the
      relevant literature. In addition warning signs of this forensically relevant
      syndrome and a strategy for the management of suspected MSBP cases are described.

PMID- 15578198
TI  - Estimation of postmortem metabolic changes in porcine brain tissue using 1H-MR
      spectroscopy--preliminary results.
AB  - To investigate the potential for estimating the time since death by monitoring
      the evolution of different metabolites in brain tissue by (1)H-MRS, an animal
      model using pig heads was established. The maximum examination interval was 3
      weeks. Within this time interval spectra revealed different compositions of
      metabolites, including metabolites observed in the normal brain and as products
      of bacterial decomposition processes (N-acetyl-aspartate 0-130 h, creatine 0-170
      h, bound trimethylammonium, e. g. choline compounds, during the whole time course
      with fluctuating intensities, lactate 0-200 h, alanine and acetate during the
      whole time course, succinate and free trimethylammonium after approx. 100 h
      postmortem). The proposed approach may offer a new method to estimate later
      postmortem intervals although these observations have to be confirmed by further
      studies.

PMID- 15578199
TI  - Bayes' theorem applied to perimetric progression detection in glaucoma: from
      specificity to positive predictive value.
AB  - PURPOSE: To estimate the specificity of a clinical evaluation of a series of
      visual fields and to calculate the positive predictive value of progression.
      METHODS: The specificity of a clinical evaluation of a series of visual fields
      was estimated using nonparametric ranking and probability calculus. The positive
      predictive value of progression was calculated using Bayes' theorem. The
      literature suggests a prior probability of progression of typically 0.10 in the
      case of one visual field per year. Three different prior probability values were
      used: 0.05, 0.10, and 0.20. Calculations were performed for a sensitivity of
      0.50, 0.80, and 1.00. RESULTS: Specificity of a clinical evaluation of a series
      of visual fields was calculated as 0.83 for four fields (two baseline fields, one
      follow-up field with suspected progression, and one confirmation of the suspected
      progression), 0.90 for five fields, and 0.95 for six fields. Positive predictive
      values ranged from 0.14 to 0.83. Positive predictive value was approximately 0.5
      for a prior probability of 0.10, a sensitivity of 0.80, and a specificity of
      0.90. CONCLUSIONS: Realistic series of visual fields that are apparently
      progressive have a positive predictive value of typically 0.5, i.e., half of them
      are stable. In the case of a high prior probability (uncontrolled glaucoma or
      long interval between successive fields), four fields may suffice to diagnose
      progression, whereas at least six fields are required if the prior probability is
      low.

PMID- 15578200
TI  - Subretinal implantation and testing of polyimide film electrodes in cats.
AB  - BACKGROUND: Progress in the field of microelectronics has led to the development
      of visual prostheses for the treatment of blinding diseases. One concept under
      investigation is an electronic subretinal prosthesis to replace the function of
      lost photoreceptors in degenerative diseases, such as retinitis pigmentosa.
      METHODS: In the subretinal prosthesis design concept, an array of stimulation
      electrodes is placed in the subretinal space. To test the feasibility of the
      concept and to determine basic stimulation parameters, wire-bound stimulation
      devices were used in acute trials for up to 12 h in three eyes in anaesthetised
      cats. These wire-bound stimulation elements were based on strips of polyimide
      film. The film strips were introduced through a sclerostomy into the vitreous
      cavity and via a retinotomy into the subretinal space during a modification of
      the standard three-port vitrectomy procedure. On entry through the retinotomy,
      the film was advanced mechanically to the desired position in the area centralis.
      Perfluorocarbon liquid (PFCL) was used to establish close contact between the
      electrode array and the outer retina. Stimulation was performed with computer
      generated sequences of current waveforms in acute trials immediately after
      surgical implantation of the stimulation film. Cortical recordings in the primary
      visual cortex were performed with electrodes placed in locations corresponding to
      the retinal stimulus site. RESULTS: All three implantations were carried out
      successfully with the stimulation array implanted beneath the outer retina of the
      area centralis of the operated eye. The retina was attached over the stimulation
      array in all cases. No cortical responses were recorded in one of the stimulation
      sessions. The results from another session revealed clear intracortical responses
      to subretinal stimulation with polyimide films. Following single-site retina
      stimulation, the estimates of spatial cortical resolution and temporal resolution
      were approximately 1 mm and 20-50 ms, respectively. DISCUSSION: Our results
      indicate that focal subretinal stimulation evokes localised spatio-temporal
      distribution of cortical responses. These findings offer hope that coarse
      restoration of vision may be feasible by subretinal electrical stimulation.

PMID- 15578201
TI  - Performance at altitude and angiotensin I-converting enzyme genotype.
AB  - The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin
      converting enzyme (ACE) gene is associated with both lower tissue ACE activity
      and elite performance at high altitude. We examined whether the onset of acute
      mountain sickness (AMS), and further performance on reaching the summit of Mt.
      Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four
      climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment
      of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again
      on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success
      in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100%
      of II individuals; P=0.048); I allele frequency for those reaching the summit was
      0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1
      appeared to be dependent on genotype (P=0.003), but with those heterozygous being
      less affected. ACE genotype was not associated either with AMS onset or severity
      on day 2. Thus, ACE I/D genotype is associated with successful high altitude
      ascent in this prospective study-an association not explicable by genotype
      dependence of AMS onset or severity. Values are given as mean (SD) unless
      otherwise stated.

PMID- 15578202
TI  - Differences in the force/endurance relationship between young and older men.
AB  - The aim of the present study was to ascertain if in six young (23-35 years) and
      in six older (70-72 years) healthy men matched for comparable absolute and
      specific maximal force of the dominant elbow flexors, differences in isometric
      endurance, myoelectrical fatigability, and shortening velocity are still
      recognizable. To assess the specific force, the muscle cross sectional area (CSA)
      was determined from magnetic resonance imaging (MRI) scans. The performance of
      the elbow flexors was studied by assessing the isometric endurance times (ET) at
      different percentages of maximal isometric contraction (MVC), the average muscle
      fibre conduction velocity of action potentials (CV), and the median frequency
      (MDF) of the surface electromyogram (sEMG) of the biceps brachii. Finally, the
      torque-velocity curve was assessed by means of maximal isokinetic contractions at
      six fixed angular velocities. All data were expressed as the mean (SD). The
      results showed that: (1) the ET was longer in the older subjects at the highest
      levels of isometric contraction, independently from the absolute force; (2) the
      modifications of muscle fibre CV during isometric effort progressed less rapidly
      in the older than the younger groups, as did those of MDF; and (3) at the same
      angular velocity, the older subjects exerted less absolute force than the younger
      subjects. These results suggest an impairment of the neuromuscular system of
      older men, which is less powerful and less fatigable than that of young men.

PMID- 15578203
TI  - Effect of caffeine ingestion on lymphocyte counts and subset activation in vivo
      following strenuous cycling.
AB  - Caffeine ingestion is associated with increases in the concentration of plasma
      epinephrine and epinephrine is associated with alterations in immune cell
      trafficking and function following intensive exercise. Therefore, the purpose of
      this study was to investigate the effect of caffeine ingestion on plasma
      epinephrine concentration, lymphocyte counts and subset activation in vivo, as
      measured by the expression the CD69 surface antigen, before and after intensive
      cycling. On two occasions, following an overnight fast and 60 h abstention from
      caffeine containing foods and drinks, eight endurance trained males cycled for 90
      min at 70% <Vdot>O(2 max) 60 min after ingesting caffeine (6 mg kg(-1 )body mass;
      CAF) or placebo (PLA). Venous blood samples were collected at pre-treatment, pre
      exercise, post-exercise and 1 h post-exercise. Plasma epinephrine concentrations
      were significantly higher in CAF compared with PLA at pre-exercise [0.28 (0.05)
      nmol l(-1) versus 0.08 (0.03) nmol l(-1), P<0.01; mean (SE)] and immediately post
      exercise [1.02 (0.16) nmol l(-1) versuss 0.60 (0.13) nmol l(-1), P<0.01].
      Compared with pre-treatment, numbers of CD4(+) and CD8(+) cells decreased by 54%
      and 55%, respectively, in CAF at 1 h post-exercise (both P<0.01) but did not
      significantly differ in PLA. Compared with PLA, in CAF the percentage of
      CD4(+)CD69(+) cells was 5-fold higher at post-exercise (P<0.05) and 5.5-fold
      higher at 1 h post-exercise (P=0.01). Compared with PLA, in CAF the percentage of
      CD8(+)CD69(+) cells was 2-fold higher at pre-exercise (P<0.05) and 1.7-fold
      higher at post-exercise (P<0.05). These findings suggest that caffeine ingestion
      is associated with alterations in lymphocyte subset trafficking and expression of
      CD69 in vivo following prolonged, intensive exercise.

PMID- 15578204
TI  - Acute passive stretching alters the mechanical properties of human plantar
      flexors and the optimal angle for maximal voluntary contraction.
AB  - The purpose of this study was to investigate whether acute passive stretching
      (APS) reduced maximal isometric voluntary contraction (MVC) of the plantar
      flexors (PF) and if so, by what mechanisms. The PF in 15 female volunteers were
      stretched for 10 min (5 x 120 s) by a torque motor to within 2 degrees of maximum
      dorsiflexion (D) range of motion (ROM). MVC with twitch interpolation, maximal
      Hoffmann reflex (H(max)) and compound action potentials (M(max)) were recorded at
      20 degrees D. Stretch reflexes (SR) were mechanically induced at 200 degrees s(
      1) between 0 degrees and 10 degrees ( )D and SR torque and EMG amplitude were
      determined. All tests were assessed pre- (pre) and post-APS (post-test(1)). MVC,
      SR, and M(max) were again assessed after additional stretch was applied [mean 26
      (1) degrees D; post-test(2)] to test if the optimal angle had been altered. EMG
      was recorded from soleus (SOL), medial gastrocnemius (MG) and tibialis anterior
      (TA) using bipolar surface electrodes. APS resulted in a 27% decrease in mean
      peak passive torque (P<0.05). MVC and SR torque were 7% (P<0.05) and 13% lower at
      post-test(1) (P<0.05), respectively. SR EMG amplitude of SOL and MG was reduced
      by 27% (P<0.05) and 22% (P<0.05), respectively. The H(max)/M(max) EMG and
      H(max)/M(max) torque ratios were unchanged at post-test(1). At post-test(2), MVC
      and SR EMG recovered to pre-APS values, while the SR and M(max) torque increased
      by 19% and 13%, respectively (P<0.05). The decrease in MVC during post-test(1)
      was attributed to changes in the mechanical properties of PF and not to reduced
      muscle activation.

PMID- 15578205
TI  - Non-linear cardiac output dynamics during ramp-incremental cycle ergometry.
AB  - Published literature asserts that cardiac output (Q(.) = V(.) >O(2)x1/C((a
      v))O(2)) increases as a linear function of oxygen uptake with a slope of
      approximately 5-6 during constant work rate exercise. However, we have previously
      demonstrated that C((a-v))O(2) has a linear relationship as a function of
      V(.)O(2) during progressively increasing work rate incremental exercise.
      Therefore, we hypothesized that Q(.) may indeed have a non-linear relationship
      with respect to V(.)O(2) during incremental, non-steady state exercise. To
      investigate this hypothesis, we performed five maximal progressive work rate
      exercise studies in healthy human subjects. Q(.) was determined every minute
      during exercise using measured breath-by-breath V(.) >O(2), and arterial and
      pulmonary artery measurements of PO(2), hemoglobin saturation, and content. Q(.)
      was plotted as a function of V(.) >O(2) and the linear and non-linear (first
      order exponential and hyperbolic) fits determined for each subject. Tests for
      linearity were performed by assessing the significance of the quadratic terms
      added to the linear relation using least squares estimation in linear regression.
      Linearity was inadequate in all cases (group P<0.0001). We conclude that cardiac
      output is a non-linear function of V(.)O(2 )during ramp-incremental exercise; the
      pattern of non-linearity suggests that while the kinetics of Q(.) > are faster
      than those of V(.) >O(2) they progressively slow as work rate (and V(.) >O(2))
      increases.

PMID- 15578206
TI  - Respiratory kinematics by optoelectronic plethysmography during exercise in men
      and women.
AB  - Gender differences in resting pulmonary function are attributable to the smaller
      lung volumes in women relative to men. We sought to investigate whether the
      pattern of response in operational lung volumes during exercise is different
      between men and women of similar fitness levels. Breath-by-breath volume changes
      of the entire chest wall ( V(.)( CW)) and its rib cage ( V(.)( Rc)) and abdominal
      ( V(.)( Ab)) compartments were studied by optoelectronic plethysmography in 15
      healthy subjects (10 men) who underwent a symptom-limited ( W (peak)) incremental
      bicycle test. The pattern of change in end-inspiratory and end-expiratory V(.)(
      CW) ( V(.)( CW,EI) and V(.)( CW,EE), respectively) did not differ between the
      sexes. With increasing workload the decrease in V(.)( CW,EE) was almost entirely
      attributable to a reduction in end-expiratory V(.)( Ab), whereas the increase in
      V(.)( CW,EI) was due to the increase in end-inspiratory V(.)( Rc) in both sexes.
      In men, at W (peak) tidal volume [ V(.)( T), 2.7 (0.2) l] and inspiratory
      capacity [IC, 3.4 (0.2) l] were significantly greater than in women [1.8 (0.2)
      and 2.6 (0.2) l, respectively]. However, after controlling for lung size using
      forced vital capacity (FVC) as a surrogate, the differences between men and women
      were eliminated [ V(.)( T) /FVC 49 (3) and 45 (3) respectively, and IC/FVC 63 (2)
      and 65 (3) respectively]. All data are presented as mean (SE). In both men and
      women the contribution of the rib cage compartment to V(.)( T) expansion was
      significantly greater than that of the abdominal compartment. We conclude that
      gender differences in operational lung volumes in response to progressive
      exercise are principally attributable to differences related to lung size,
      whereas compartmental chest wall kinematics do not differ among sexes.

PMID- 15578207
TI  - Gait characteristics in people with type 2 diabetes mellitus.
AB  - Sixteen control subjects and 15 subjects with type 2 diabetes were examined to
      compare gait characteristics during walking in a linear path and in turns of 0.33
      and 0.66 m diameter. Subjects were excluded if there was diminished sensation in
      the feet or impairment of strength in the legs. This was done to isolate the
      effect of diabetes gait independent of loss of sensation. Gait was assessed
      through contact sensors on the foot, video, and two axis accelerometers mounted
      bilaterally on the head, shoulders, hips, knees and ankles. The results of these
      experiments showed that subjects with diabetes walked significantly slower
      (P<0.05) than control subjects and with a wider stance (P<0.01), both for walking
      in a linear path (velocity of subjects with diabetes was 62.2% that of controls
      and stance was 134.9% wider than controls) and when making turns (velocity 50.6%
      of controls and stance 120.1% wider than that of controls). Accelerometry showed
      increased flexion/extension and lateral movement of the major joints in subjects
      with diabetes during both walking in a linear path and turns compared to control
      subjects. Part of the increased movement at the joints in the subjects with
      diabetes was due to tremor in both the 8 Hz and 16 Hz bands. These findings
      suggest that at least some of the increased joint movement during walking in
      people with diabetes is likely neurological in origin and not related to muscle
      weakness or loss of sensation in the feet.

PMID- 15578208
TI  - Metabolic response to prolonged cycling with (13)C-glucose ingestion following
      downhill running.
AB  - The purpose of this study was to describe the effect of muscle damage and delayed
      onset muscle soreness (DOMS) on the metabolic response during a subsequent period
      of prolonged concentric exercise (120 min, approximately 61% V(.)O(2max), on a
      cycle ergometer), with ingestion of 3 g of (13)C-glucose/kg body mass. We
      hypothesized that the oxidation of plasma and exogenous glucose would be reduced,
      while the oxidation of glucose arising from muscle glycogen would be increased.
      Six male subjects were studied during exercise in a control situation and 2 days
      following downhill running, at a time when plasma creatine kinase (CK) activity
      was increased, and DOMS was present. Carbohydrate and lipid oxidation were
      computed from indirect respiratory calorimetry corrected for protein oxidation,
      while the oxidation of plasma glucose and muscle glycogen were computed from
      V(.)(13)CO(2) and the ratio of (13)C/(12)C in the plasma glucose. All data were
      presented as the mean and the standard error of the mean. The oxidation of
      protein (approximately 6% energy yield, in the control and the experimental
      trial), lipid (approximately 15 and approximately 18%), and carbohydrate
      (approximately 79 and approximately 76%), as well as that of plasma glucose
      (approximately 41 and approximately 46%), glucose from the liver (approximately
      12 and approximately 14%), and glucose from muscle glycogen (approximately 38 and
      approximately 31%) were not significantly different between the control and
      experimental (DOMS) trials. The response of the plasma glucose, insulin, lactate,
      and free fatty acid concentrations was not modified by the previous eccentric
      exercise. These results indicate that the metabolic response to prolonged
      concentric exercise is not modified by muscle damage and DOMS resulting from a
      bout of eccentric exercise performed 2 days before.

PMID- 15578211
TI  - Survival after surgical management of pancreatic adenocarcinoma: does curative
      and radical surgery truly exist?
AB  - Surgery for pancreatic cancer offers a low success rate but it provides the only
      likelihood of cure. Modern series show that, in experienced hands, the standard
      Whipple procedure is associated with a 5-year survival of 10%-20%, with a
      perioperative mortality rate of less than 5%. Most patients, however, will
      develop recurrent disease within 2 years after curative treatment. This occurs,
      usually, either at the site of resection or in the liver. This suggests the
      presence of micrometastases at the time of operation. Negative lymph nodes are
      the strongest predictor for long-term survival. Other predictors for a favourable
      outcome are tumour size, radical surgery and a histopathologically well
      differentiated tumour. Adjuvant therapy has, so far, shown only modest results,
      with 5FU chemotherapy, to date, the only proven agent able to increase survival.
      Nowadays, the choice of therapy should be based on histopathological assessment
      of the tumour. Knowledge of the molecular basis of pancreatic cancer has led to
      various discoveries concerning its character and type. Well-known examples of
      genetic mutations in adenocarcinoma of the pancreas are k-ras, p53, p16, DPC4.
      Use of molecular diagnostics and markers in the assessment of tumour biology may,
      in future, reveal important subtypes of this type of tumour and may possibly
      predict the response to adjuvant therapy. Defining the subtypes of pancreatic
      cancer will, hopefully, lead to target-specific, less toxic and finally more
      effective therapies. Long-term survival is observed in only a very small group of
      patients, contradicting the published actuarial survival rates of 10%-45%.
      Assessment of clinical benefit from surgery and adjuvant therapy should,
      therefore, not only be based on actuarial survival but also on progression-free
      survival, actual survival, median survival and quality of life (QOL) indicators.
      Survival in surgical series is usually calculated by actuarial methods. If there
      is no information on the total number of patients and the number of actual
      survivors, and no clear definition of the subset of patients, actuarial survival
      curves can prove to be misleading. Proper assessment of QOL after surgery and
      adjuvant therapy is of the utmost importance, as improvements in survival rates
      have, so far, proved to be disappointing.

PMID- 15578212
TI  - Regulation of cardiac shal-related potassium channel Kv 4.3 by serum- and
      glucocorticoid-inducible kinase isoforms in Xenopus oocytes.
AB  - The human cardiac transient outward potassium current I(to) is formed by co
      assembly of voltage-dependent K(+) channel (Kv 4.3) pore-forming alpha-subunits
      with differently spliced K channel interacting protein (KChIP) accessory
      proteins. I(to) is of considerable importance for the normal course of the
      cardiac ventricular action potential. The present study was performed to
      determine whether isoforms of the serum- and glucocorticoid-inducible kinase
      (SGK) family influence Kv 4.3/KChIP2b channel activity in the Xenopus laevis
      heterologous expression system. Co-expression of SGK1, but not of SGK2 or SGK3,
      increased Kv 4.3/KChIP2b channel currents. The up-regulation of the current was
      not due to changes in the activation curve or changes of channel inactivation.
      The currents in oocytes expressing Kv 4.3 alone were smaller than those in Kv
      4.3/KChIP2b expressing oocytes, but were still stimulated by SGK1. The effect of
      wild-type SGK1 was mimicked by constitutively active SGK1 (SGK1 S422D) but not by
      an inactive mutant (SGK1 K127N). The current amplitude increase mediated by SGK1
      was not dependent on NEDD4.2 or RAB5, nor did it reflect increased cell surface
      expression. In conclusion, SGK1 stimulates Kv 4.3 potassium channels expressed in
      Xenopus oocytes by a novel mechanism distinct from the known NEDD4.2-dependent
      pathway.

PMID- 15578213
TI  - An air-molding technique for fabricating PDMS planar patch-clamp electrodes.
AB  - We present a new technique for fabricating planar patch electrodes in the
      laboratory. Planar electrodes are micromolded using a micron-sized stream of air
      to define an aperture in the silicone elastomer, polydimethylsiloxane (PDMS). We
      have previously demonstrated that planar PDMS electrodes make excellent patch
      electrodes after surface modification. We demonstrate single-channel measurements
      of the rSlo channel in Xenopus oocytes and whole-cell measurements in CHO and RBL
      mammalian cell lines, using planar PDMS electrodes.

PMID- 15578214
TI  - Cellular re-distribution of flavin-containing polyamine oxidase in
      differentiating root and mesocotyl of Zea mays L. seedlings.
AB  - Plant polyamine oxidases (PAOs; EC 1.5.3.11) are hydrogen peroxide-producing
      enzymes supposedly involved in cell-wall differentiation processes and defence
      responses. Maize (Zea mays L.) PAO (MPAO) is a 53 kDa secretory glycoprotein,
      abundant in primary and secondary cell walls of several tissues. Using
      biochemical, histochemical, ultrastructural and immunocytochemical techniques,
      the distribution and sub-cellular compartmentalisation of MPAO in the primary
      root and mesocotyl of seedlings at different maturation stages or after growth
      under varying light conditions were analysed. In apical root tissues, MPAO
      immunoreactivity was mainly detected in the cytoplasmic compartment, while a
      lower immunoreactivity was observed in the cell walls. In the more mature, basal
      part of the root, intense immunogold labelling was found in the primary and
      secondary walls of protoxylem precursors and vessels, while endodermal cells and
      living metaxylem precursors were immunopositive both in their walls and in their
      thin cytoplasmic compartments. A re-distribution of MPAO protein from the
      cytoplasm toward the primary and secondary walls was also recognised when
      immunoreactivity of basal root tissues from 3-day-old seedlings was compared with
      that detected in 11-day-old tissues. Accordingly, biochemical analyses revealed
      MPAO entrapment in the extracellular matrix of mature tissues. In the mesocotyl,
      an enrichment of MPAO immunolabelling in the cell wall of protoxylem, metaxylem
      and epidermal tissues, as a function of light exposure, was observed. Taken
      together, these data support the hypothesised role of PAOs in cell-wall
      maturation. Moreover, the relevant intraprotoplasmic MPAO localisation observed
      mainly in differentiating root tissues suggests an additional role in
      intracellular production of hydrogen peroxide.

PMID- 15578215
TI  - A conserved functional role of pectic polymers in stomatal guard cells from a
      range of plant species.
AB  - Guard cell walls combine exceptional strength and flexibility in order to
      accommodate the turgor pressure-driven changes in size and shape that underlie
      the opening and closing of stomatal pores. To investigate the molecular basis of
      these exceptional qualities, we have used a combination of compositional and
      functional analyses in three different plant species. We show that comparisons of
      FTIR spectra from stomatal guard cells and those of other epidermal cells
      indicate a number of clear differences in cell-wall composition. The most obvious
      characteristics are that stomatal guard cells are enriched in phenolic esters of
      pectins. This enrichment is apparent in guard cells from Vicia faba (possessing a
      type I cell wall) and Commelina communis and Zea mays (having a type II wall). We
      further show that these common defining elements of guard cell walls have
      conserved functional roles. As previously reported in C. communis, we show that
      enzymatic modification of the pectin network in guard cell walls in both V. faba
      and Z. mays has profound effects on stomatal function. In all three species,
      incubation of epidermal strips with a combination of pectin methyl esterase and
      endopolygalacturonase (EPG) caused an increase in stomatal aperture on opening.
      This effect was not seen when strips were incubated with EPG alone indicating
      that the methyl-esterified fraction of homogalacturonan is key to this effect. In
      contrast, arabinanase treatment, and incubation with feruloyl esterase both
      impeded stomatal opening. It therefore appears that pectins and phenolic esters
      have a conserved functional role in guard cell walls even in grass species with
      type II walls, which characteristically are composed of low levels of pectins.

PMID- 15578216
TI  - Novel tissue preparation method and cell-specific marker for laser
      microdissection of Arabidopsis mature leaf.
AB  - Laser microdissection (LMD) is a powerful tool to isolate pure cell populations
      from heterogeneous tissues. This system has been successfully used for animal
      research; however, the reports of its application to plant tissues remain
      limited. One of the challenges of LMD for plant material is the tissue
      preparation. Although cryosectioning is commonly used for animal tissues, this is
      not a desirable method for fragile plant material with large central vacuoles.
      While paraffin preparation provides high histological quality and stability, the
      procedure is highly time consuming and may result in degradation of molecules of
      interest. In addition, conventional fixation and paraffin preparation methods do
      not preserve the structural integrity of very delicate plant tissues such as
      mature Arabidopsis thaliana leaves. Here, we used the rapid microwave paraffin
      preparation method with no fixative for preparation of Arabidopsis leaf tissue
      for LMD. This method resulted in Arabidopsis leaf sections with excellent
      preservation of leaf internal structure as evidenced by well-defined vascular
      bundles, phloem, and chloroplasts, and expanded and rounded epidermal cells. RNA
      extracted from leaf epidermal and mesophyll cells was of sufficient yield and
      specificity to use in downstream applications such as microarray analysis of the
      amplified mRNA. We employed the mesophyll cell-specific molecular marker,
      chloroplastic carbonic anhydrase, and developed an epidermal cell-specific
      marker, the very-long-chain fatty acid-condensing enzyme, CUT1, to assess
      specificity of harvested Arabidopsis leaf cell types by reverse transcription
      polymerase chain reaction. The described method is also likely to be superior for
      the preparation of other fragile botanical tissue for LMD and downstream
      applications.

PMID- 15578218
TI  - Targeted site-directed mutagenesis of a heme oxygenase locus by gene replacement
      in the moss Ceratodon purpureus.
AB  - The moss Physcomitrella patens is so far the only plant species in which it is
      possible for nuclear genes to be modified by homologous recombination at a
      reasonably efficiency. Here we describe the use of homologous recombination for
      another moss, Ceratodon purpureus. Our approach is based on the repair of the
      ptr116 mutant allele. In this mutant, codon 31 of the heme oxygenase gene CpHO1
      is mutated to a stop codon. Heme oxygenase is necessary for the conversion of
      heme to biliverdin, the precursor of the phytochrome chromophore. Thus, in ptr116
      the phytochrome-mediated responses of phototropism, chlorophyll accumulation and
      branching are lost. Protoplast transformation with DNA encoding the wild-type
      protein resulted in a rescue of 0.8% of regenerated protoplasts. In about half of
      the analyzed lines, formation of CpHO1 concatemers was observed at the CpHO1
      locus, whereas in the other half, the mutant CpHO1 gene was replaced by a single
      DNA copy. This gene repair led to the exchange of single bases, and thus provides
      the first demonstration of efficient site-directed mutagenesis in a plant nuclear
      genome. Our studies also revealed an effective mechanism for gene inactivation in
      Ceratodon. When wild-type protoplasts were transformed with intact or modified
      CpHO1 genes, approximately 40% of regenerated protoplasts showed the ptr
      phenotype.

PMID- 15578219
TI  - Hot-water epilepsy: a new Caucasian case.

PMID- 15578220
TI  - Fomepizole as a therapeutic strategy in paediatric methanol poisoning. A case
      report and review of the literature.
AB  - Methanol poisoning is not frequently observed in children; however, without
      treatment, serious intoxication can be complicated by visual impairment, coma,
      metabolic acidosis, respiratory and circulatory insufficiency and death.
      Treatment in a paediatric intensive care is therefore compulsory. Methanol is
      metabolised in the liver by alcohol dehydrogenase to the toxic metabolites
      formaldehyde and formic acid. Classically, ethanol is given as a competitive
      inhibitor in order to avoid the formation of these compounds. We report on the
      use of fomepizole (4-methylpyrazole),a new and potent inhibitor of alcohol
      dehydrogenase, in a 3-year-old boy after the intake of a toxic amount of
      methanol. The course was uneventful and the use of fomepizole was not accompanied
      by any side-effects. An overview is given of all cases of paediatric poisoning in
      which fomepizole was used. CONCLUSION: Fomepizole seems to be a safe and valid
      alternative to ethanol in cases of paediatric methanol poisoning.

PMID- 15578221
TI  - Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors.
AB  - Previous studies have shown that proteasome inhibitors are novel agents for
      chemotherapy of human African trypanosomiasis or sleeping sickness. In this
      study, five peptide trileucine methyl vinyl sulfones with different N-terminal
      substituents were tested for their trypanocidal activities in vitro using culture
      adapted bloodstream forms of Trypanosoma brucei. Two inhibitors displayed
      promising anti-trypanosomal activities with ED50 values in the sub-micromolar
      range. Higher trypanocidal activity of the compounds generally corresponded to a
      higher k(obs)/[I] value for inhibition of the trypsin-like activity but not for
      the inhibition of the chymotrypsin-like activity of the proteasome. These data
      suggest that inhibitors with strong activity against the trypsin-like activity of
      the proteasome are the rational choice for future anti-sleeping sickness drug
      development.

PMID- 15578217
TI  - Transcriptome analysis of alfalfa glandular trichomes.
AB  - Glandular trichomes are a major site of plant natural product synthesis and
      accumulation for protection against insect predation. However, to date few
      studies have attempted to obtain a global view of trichome gene expression. Two
      contrasting approaches have been adopted to investigate genes expressed in
      glandular trichomes from alfalfa (Medicago sativa L.). In the first approach,
      5,674 clones from an alfalfa glandular trichome cDNA library were sequenced. The
      most highly abundant expressed sequence tag (EST) corresponded to a lipid
      transfer protein. The presence of ESTs corresponding to enzymes for all steps in
      the biosynthesis of flavonoids suggests that these are important metabolites in
      alfalfa trichome biology, as confirmed by histochemistry and metabolite
      profiling. No ESTs corresponded to enzymes of cyclized terpenoid biosynthesis. In
      a second approach, microarray analysis was used to compare levels of alfalfa
      transcripts corresponding to 16,086 Medicago truncatula A17 genes in stems with
      and without trichomes. This revealed over 1,000 genes with strong preferential
      expression in the trichome fraction of the stem, 70% of which are of unknown
      function. These define a class of genes that are not trichome-specific, since M.
      truncatula A17 does not itself have glandular trichomes, but has potential
      importance for trichome function within the stem.

PMID- 15578222
TI  - A H2O2-producing glyoxal oxidase is required for filamentous growth and
      pathogenicity in Ustilago maydis.
AB  - In the phytopathogenic fungus Ustilago maydis the mating-type loci control the
      transition from yeast-like to filamentous growth required for pathogenic
      development. In a large REMI (restriction enzyme mediated integration) screen,
      non-pathogenic mutants were isolated in a haploid strain that had been engineered
      to be pathogenic. In one of these mutants, which showed a specific morphological
      phenotype, the tagged gene, glo1 , was found to encode a product that is highly
      homologous to a glyoxal oxidase gene from the wood-rot fungus Phanerochaete
      chrysosporium. Glyoxal oxidase homologues are found in human, plant pathogenic
      fungi and in plants, but not in other mammals or yeasts. To confirm the function
      of the glo1 gene, null mutations were generated in compatible haploid U. maydis
      strains. In crosses null mutants were unable to generate filamentous dikaryons,
      and were completely non-pathogenic. Using a Glo1-overproducing strain we
      demonstrated that Glo1 is membrane bound, oxidizes a series of small aldehydes (<
      C4) and produces H2O2. The enzyme needs to be activated, presumably by auto
      oxidation, to show full activity. A potential role for Glo1 during filamentous
      growth and pathogenic development of U. maydis is proposed.

PMID- 15578223
TI  - The USH1C 216G-->A splice-site mutation results in a 35-base-pair deletion.
AB  - Usher syndrome is characterized by profound hearing loss and retinal
      degeneration. A splice-site mutation, 216G-->A, in exon 3 of USH1C is associated
      with Acadian Usher type IC. This mutation was reported to create an in-frame
      deletion of 39 base pairs (bp), resulting in an unstable transcript. By RT-PCR
      analysis of 216A and 216G constructs transfected into HeLa cells and also of
      patient cell lines, we have demonstrated a frame-shift deletion of 35 bp, not 39
      bp. Thus, the instability of the USH1C mRNA is explained by the 216G-->A out-of
      frame splice site mutation.

PMID- 15578224
TI  - Variation in meiotic recombination frequencies among human males.
AB  - Meiotic recombination is essential for the segregation of homologous chromosomes
      and the formation of normal haploid gametes. Little is known about patterns of
      meiotic recombination in human germ cells or the mechanisms that control these
      patterns. Here, newly developed immunofluorescence techniques, based on the
      detection of MLH1 (a DNA mismatch repair protein) foci on synaptonemal complexes
      (SCs) at prophase I of meiosis, were used to examine recombination in human
      spermatocytes. The mean number of MLH1 foci per cell in all donors was 48.0 with
      range from 21 to 65. Remarkable variation in the recombination frequency was
      noted among 11 normal individuals: the mean frequencies of chromosomal
      recombination foci ranged from a low of 42.5 to a high of 55.0 exchanges. Donor
      age did not contribute to this variation. There was no correlation between this
      variation and the frequency of gaps (discontinuities) or splits (unpaired
      chromosome regions) in the SCs. The mean percentage of cells with gaps was 35%
      (range: 20% to 58%) and with splits was 7% (range: 0% to 37%). Bivalents without
      a recombination focus were rare, with a frequency of only 0.3%. Thus, achiasmate
      chromosomes appear to be rare in human male meiosis.

PMID- 15578225
TI  - Bone marrow subendosteal microenvironment harbours functionally distinct
      haemosupportive stromal cell populations.
AB  - In adult animals, bone marrow is the major site of blood cell production, which
      is controlled by interactions between the local stroma and blood cell
      progenitors. The endosteal/subendosteal environment comprises bone-lining and
      adjacent reticular cells and sustains haemopoietic stem cell (HSC) self-renewal,
      proliferation and differentiation. We have questioned the specific role of each
      of these stroma cells in controlling HSC fate. We have isolated two distinct
      stroma-cell populations containing subendosteal reticulocytes (F-RET) and
      osteoblasts (F-OST) from periosteum-free fragments of murine femurs by a two-step
      collagenase-digestion procedure. Both populations produce similar extracellular
      matrix (collagen I, laminin, fibronectin, decorin), except for collagen IV, which
      is low in F-OST. They also express osteogenic markers: osteopontin, osteonectin,
      bone sialoprotein and alkaline phosphatase (ALP). The quantity and activity of
      ALP are however higher in F-OST. When co-cultured with bone marrow mononuclear
      cells or lineage-negative haemopoietic progenitors, F-OST stroma induces low
      proliferation and high maintenance of early haemopoietic progenitors, whereas F
      RET stroma induces high short-term proliferation and differentiation. Analysis by
      reverse transcription/polymerase chain reaction has revealed higher levels of
      Jagged-1 expression by F-OST cells than by the F-RET population. Thus, two
      adjacent stroma cells (subendosteal and endosteal) play distinct roles in
      controlling the stem-cell capacity and fate of HSC and probably contribute
      distinctly to HSC niche formation.

PMID- 15578226
TI  - Forest soil respiration rate and delta13C is regulated by recent above ground
      weather conditions.
AB  - Soil respiration, a key component of the global carbon cycle, is a major source
      of uncertainty when estimating terrestrial carbon budgets at ecosystem and higher
      levels. Rates of soil and root respiration are assumed to be dependent on soil
      temperature and soil moisture yet these factors often barely explain half the
      seasonal variation in soil respiration. We here found that soil moisture (range
      16.5-27.6% of dry weight) and soil temperature (range 8-17.5 degrees C) together
      explained 55% of the variance (cross-validated explained variance; Q2) in soil
      respiration rate (range 1.0-3.4 micromol C m(-2) s(-1)) in a Norway spruce (Picea
      abies) forest. We hypothesised that this was due to that the two components of
      soil respiration, root respiration and decomposition, are governed by different
      factors. We therefore applied PLS (partial least squares regression) multivariate
      modelling in which we, together with below ground temperature and soil moisture,
      used the recent above ground air temperature and air humidity (vapour pressure
      deficit, VPD) conditions as x-variables. We found that air temperature and VPD
      data collected 1-4 days before respiration measurements explained 86% of the
      seasonal variation in the rate of soil respiration. The addition of soil moisture
      and soil temperature to the PLS-models increased the Q2 to 93%. delta13C analysis
      of soil respiration supported the hypotheses that there was a fast flux of
      photosynthates to root respiration and a dependence on recent above ground
      weather conditions. Taken together, our results suggest that shoot activities the
      preceding 1-6 days influence, to a large degree, the rate of root and soil
      respiration. We propose this above ground influence on soil respiration to be
      proportionally largest in the middle of the growing season and in situations when
      there is large day-to-day shifts in the above ground weather conditions. During
      such conditions soil temperature may not exert the major control on root
      respiration.

PMID- 15578227
TI  - Non-structural carbohydrate pools in a tropical forest.
AB  - The pool size of mobile, i.e. non-structural carbohydrates (NSC) in trees
      reflects the balance between net photosynthetic carbon uptake (source) and
      irreversible investments in structures or loss of carbon (sink). The seasonal
      variation of NSC concentration should reflect the sink/source relationship,
      provided all tissues from root to crown tops are considered. Using the
      Smithsonian canopy crane in Panama we studied NSC concentrations in a semi
      deciduous tropical forest over 22 months. In the 9 most intensively studied
      species (out of the 17 investigated), we found higher NSC concentrations (starch,
      glucose, fructose, sucrose) across all species and organs in the dry season than
      in the wet season (NSC 7.2% vs 5.8% of dry matter in leaves, 8.8/6.0 in branches,
      9.7/8.5 in stems, 8.3/6.4 in coarse and 3.9/2.2 in fine roots). Since this
      increase was due to starch only, we attribute this to drought-constrained growth
      (photosynthesis less affected by drought than sink activity). Species-specific
      phenological rhythms (leafing or fruiting) did not overturn these seasonal
      trends. Most of the stem volume (diameter at breast height around 40 cm) stores
      NSC. We present the first whole forest estimate of NSC pool size, assuming a 200
      t ha(-1) forest biomass: 8% of this i.e. ca. 16 t ha(-1) is NSC, with ca. 13 t
      ha(-1) in stems and branches, ca. 0.5 and 2.8 t ha(-1) in leaves and roots.
      Starch alone (ca. 10.5 t ha(-1)) accounts for far more C than would be needed to
      replace the total leaf canopy without additional photosynthesis. NSC never passed
      through a period of significant depletion. Leaf flushing did not draw heavily
      upon NSC pools. Overall, the data imply a high carbon supply status of this
      forest and that growth during the dry season is not carbon limited. Rather, water
      shortage seems to limit carbon investment (new tissue formation) directly,
      leaving little leeway for a direct CO2 fertilization effects.

PMID- 15578228
TI  - Do sibling tits (Parus major, P. caeruleus) disperse over similar distances and
      in similar directions?
AB  - We studied dispersal movements by sibling pairs of great tits, Parus major, and
      blue tits, P. caeruleus, in a patchy environment, in order to test whether
      siblings are more similar in dispersal than expected by chance. Because of
      possible common environmental effects due to the heterogeneity and finiteness of
      the study area, we compared the similarity among siblings with the similarity
      between each sibling and an unrelated bird that fledged in the same patch and
      year, as close to the siblings' nest as possible. Siblings of both species were
      not more similar in dispersal distance than they were to control birds. However,
      great tit siblings dispersed in similar directions compared to control birds, and
      this result was not affected by the degree of matching between sibling and
      control birds. As a consequence, siblings ended up breeding at closer distances
      from one another than control birds. Heritability values calculated from parent
      offspring regressions were close to zero, suggesting that there is no additive
      genetic variance for dispersal distance or dispersal direction. We propose that
      similarity in dispersal direction originates from association of siblings during
      dispersal or during activities that influence the choice of direction, such as
      postfledging family movements. Our results show that non-independence in the
      choice of dispersal direction by siblings may influence small-scale kin structure
      in this population with high local recruitment.

PMID- 15578229
TI  - Simple and rapid determination of metabolite content in plant cell culture medium
      using an FT-IR/ATR method.
AB  - A simple, rapid and accurate mid-infrared (MIR) spectroscopic method for
      simultaneously determining the product (ethanol) content and the nutrient (sugar)
      content in plant-cell culture media was developed using a Fourier transform
      infrared (FT-IR) spectrometer equipped with an attenuated total reflectance (ATR)
      accessory. We assessed the potential of this method by comparing it to a high
      performance liquid chromatography (HPLC) method, and using the developed method
      to measure the ethanol and sugar contents simultaneously in liquid culture media
      with rice and tabacum cell suspensions, respectively. The experimental results
      suggest that the sugar consumption and ethanol production behaviors of the plant
      cell suspensions can be non-destructively and simultaneously monitored using the
      developed method. Furthermore, the spectroscopic method provided in this study
      could be developed into a technique that could be used to analyze the overall
      kinetics of the metabolism of the plant cell suspensions.

PMID- 15578230
TI  - Control of endotoxin release in Escherichia coli fed-batch cultures.
AB  - High amounts of outer membrane (OM) components were released in glucose-limited
      fed-batch (GLFB) cultures at 37 degrees C at specific growth rates approaching
      0.05 h(-1). Endotoxin analyses from a 20 degrees C GLFB culture gave similar
      results. An alternative fermentation technique, the temperature-limited fed-batch
      (TLFB) technique, reduced the endotoxin concentration in a culture with a biomass
      concentration of 30 g l(-1) from the 850 mg l(-1) in traditional GLFB cultures to
      about 20 mg l(-1). The TLFB technique uses the temperature to regulate the
      dissolved oxygen tension, while all substrate components are unregulated. It
      appears to be severe glucose limitation that triggers the extensive release of
      endotoxins rather than a low growth rate. Furthermore, it is not the low
      temperature that stabilizes the OM when using the TLFB technique. Simulations and
      experimental data show that this technique results in the same biomass
      productivity as the GLFB technique.

PMID- 15578231
TI  - Neural network modeling and control of type 1 diabetes mellitus.
AB  - This paper presents a developed and validated dynamic simulation model of type 1
      diabetes, that simulates the progression of the disease and the two term
      controller that is responsible for the insulin released to stabilize the glucose
      level. The modeling and simulation of type 1 diabetes mellitus is based on an
      artificial neural network approach. The methodology builds upon an existing rich
      database on the progression of type 1 diabetes for a group of diabetic patients.
      The model was found to perform well at estimating the next glucose level over
      time without control. A neural controller that mimics the pancreas secretion of
      insulin into the body was also developed. This controller is of the two term
      type: one stage is responsible for short-term and the other for mid-term insulin
      delivery. It was found that the controller designed predicts an adequate amount
      of insulin that should be delivered into the body to obtain a normalization of
      the elevated glucose level. This helps to achieve the main objective of insulin
      therapy: to obtain an accurate estimate of the amount of insulin to be delivered
      in order to compensate for the increase in glucose concentration.

PMID- 15578232
TI  - [Organized pain management in the DRG reimbursement system].
AB  - Multidisciplinary pain management in pain centers can only be guaranteed if the
      DRG reimbursement system takes into account the multiple risk factors. The German
      pain associations prospectively analyzed clinical and administrative (DRG
      related) data sets (n=3943) of inpatient and day care pain treatment facilities.
      The index diagnoses of 84% of the patient sample were grouped into nine basic
      DRGs. The most frequent pain procedure code was 8-918 ("multimodal pain
      management"). The minimal length of stay for this code set to 7 days was 17.2
      days for the study sample. The DRG grouper software 2003 categorized 68.6% of the
      patients into PCCL 0 despite the proven complexity of risks and secondary
      diseases. The mean case weight in the sample was set at about 1. The pain-related
      data set analyzing pain severity, chronicity, and its influence on various
      functions emphasizes the total severity and burden of disease and thus the
      necessity for multimodal pain management. The German pain societies carried the
      motion that a new complex ICD code for chronic pain (with biopsychosocial
      consequences) should be established in the German Modification of the ICD. The
      new ICD code F62.80 and the procedure code 8-918 had not yet been implemented
      into the German DRG algorithm. Due to modifications in DRG systematics and the
      DRG algorithm, to be activated in 2005, the procedure code 8-918 will now
      automatically trigger into four special basic pain DRGs corresponding to the
      index pain diagnosis.

PMID- 15578233
TI  - Seasonality of alcohol-related phenomena in Estonia.
AB  - We studied alcohol consumption and its consequences as a seasonal phenomenon in
      Estonia and analysed the social and environmental factors that may cause its
      seasonal rhythm. There are two important questions when researching the
      seasonality of human activities: (1) whether it is caused by natural or social
      factors, and (2) whether the impact of the factors is direct or indirect. Often
      the seasonality of social phenomena is caused by social factors, but the
      triggering mechanisms are related to environmental factors like temperature,
      precipitation, and radiation via the circannual calendar. The indicators of
      alcohol consumption in the current paper are grouped as: (1) pre-consumption
      phenomena, i.e. production, tax and excise, sales (beer, wine and vodka are
      analysed separately), and (2) post-consumption phenomena, i.e. alcohol-related
      crime and traffic accidents and the number of people detained in lockups and
      admitted to alcohol treatment clinics. In addition, seasonal variability in the
      amount of alcohol advertising has been studied, and a survey has been carried out
      among 87 students of Tartu University. The analysis shows that different
      phenomena related to alcohol have a clear seasonal rhythm in Estonia. The peak
      period of phenomena related to beer is in the summer, from June to August and the
      low point is during the first months of the year. Beer consumption correlates
      well with air temperature. The consumption of vodka increases sharply at the end
      of the year and in June; the production of vodka does not have a significant
      correlation with negative temperatures. The consumption of wine increases during
      summer and in December. The consequences of alcohol consumption, expressed as the
      rate of traffic accidents or the frequency of medical treatment, also show
      seasonal variability. Seasonal variability of alcohol consumption in Estonia is
      influenced by natural factors (temperature, humidity, etc.) and by social factors
      (celebrations, vacations, etc.). However, distinguishing between impacts of
      direct and indirect relationships is complicated, as they are interlinked.

PMID- 15578234
TI  - Effects of humid heat exposure in later sleep segments on sleep stages and body
      temperature in humans.
AB  - This study sought to investigate the effects of humid heat exposure in later
      sleep segments on sleep stages and body temperature in humans. The subjects were
      eight healthy males, from whom informed consent had been obtained. The
      experiments were carried out under three different sets of conditions: a control
      climate [air temperature (Ta)=26 degrees C, relative humidity (RH)=50%] (C); a
      humid heat climate (Ta=32 degrees C, RH=80%) (H); and a humid heat exposure in
      later sleep segments (C for the first 3 h 45 min, followed by a 30-min transition
      to H, which was then maintained for the last 3 h 45 min) (C-H).
      Electroencephalogram, EOG, and mental electromyogram, rectal temperature (Tre),
      and skin temperature (Tsk) were continuously measured. The total amount of
      wakefulness was significantly increased in H compared to C-H or C. Compared to C,
      wakefulness in C-H and H was significantly increased during later sleep segments.
      Tre and mean Tsk were significantly higher in H than in C-H or C. In C-H, Tsk and
      Tre increased to levels equal to those observed in H after Ta and RH increase.
      Whole body sweat loss was significantly lower in C-H and C than in H. These
      results suggest that humid heat exposure in the later sleep segment reduces
      thermal load as compared to full-night humid heat exposure. In daily life, the
      use of air conditioning in the initial sleep hours can protect sleep and
      thermoregulation.

PMID- 15578235
TI  - Symptoms, treatment and "dying peacefully" in terminally ill cancer patients: a
      prospective study.
AB  - GOALS: The aims of this study were to describe the symptoms, their treatment
      during the final months of life of terminally ill cancer patients and to assess
      characteristics of the dying process. PATIENTS AND METHODS: We used a prospective
      study design. From a representative sample of physicians who participated in a
      study of end-of-life decision making, we asked whether they were treating a
      patient with cancer whose treatment was no longer aimed at cure, whose life
      expectancy was probably longer than 1 week but no longer than 3 months and who
      would probably continue to be treated by the same physician until their death; 85
      physicians completed a monthly questionnaire until patients' deaths. RESULTS:
      Patients were confronted with an increasing amount of symptoms during the final
      months of their life. Fatigue, loss of appetite, dependency and feeling unwell
      were the most prevalent symptoms. Physical symptoms were more often treated than
      psychosocial symptoms. The number of medical disciplines involved in the
      patient's care decreased in the period before death, but the number of informal
      caregivers increased; 73% of patients died peacefully. A peaceful death was
      impeded by feelings of anxiety and loneliness but promoted by the involvement of
      children in their patients' care. CONCLUSION: The results give insight into the
      nature of suffering and factors related to the dying process of terminally ill
      cancer patients. Attention to psychosocial well-being and to the need to be with
      loved ones appears to be essential for patients' quality of life.

PMID- 15578236
TI  - Oral and intraperitoneal immunization with rotavirus 2/6 virus-like particles
      stimulates a systemic and mucosal immune response in mice.
AB  - We examined the use of a virus-like particle (VLP) as an immunogen by analysing
      the IgA and IgG response generated in serum, intestinal (fecal), pulmonary and
      uterine samples. The particle comprised two rotavirus capsid proteins (simian VP2
      and murine VP6) generated using recombinant baculovirus expression of the two
      capsid proteins, which self-assembled into particulate VLP2/6. Mice were
      immunized orally or intraperitoneally (i.p.) with 0 or 100 microg VLP2/6 with or
      without 5 microg cholera toxin adjuvant. The results showed a systemic and
      mucosal immune response to VLP2/6 when administered i.p. and, to a lesser extent,
      when delivered orally which was not dependent on adjuvant use and further proves
      the concept of VLP2/6 as an effective immunogen.

PMID- 15578237
TI  - Dengue virus type 2 in Cuba, 1997: conservation of E gene sequence in isolates
      obtained at different times during the epidemic.
AB  - It was recently reported that disease severity increased during the 1997 Cuban
      dengue 2 virus epidemic and it was suggested that this might be explained by the
      appearance of neutralization resistant escape mutants. We investigated these
      observations and ideas by sequencing 20 dengue 2 virus isolates obtained during
      the early (low case fatality rate) and the late (high case fatality rate) phases
      of the outbreak. Our results showed total conservation of the E gene sequence for
      these isolates suggesting that the selection of envelope gene escape mutants was
      not the determinant of increased disease severity. Alignment of these sequences
      with those available in GenBank, followed by Maximum likelihood phylogenetic
      analysis generated a tree, which indicated that our isolates are closely related
      to the virus that circulated in Venezuela in 1997/98 and subsequently in
      Martinique in 1998. This "American/Asian" genotype has therefore gradually
      dispersed across the Caribbean region during the past 5 years.

PMID- 15578238
TI  - Replication kinetics of different porcine circovirus 2 strains in PK-15 cells,
      fetal cardiomyocytes and macrophages.
AB  - In this in vitro study, the replication kinetics of porcine circovirus type 2
      (PCV2) in porcine alveolar macrophages (PAM) and fetal cardiomyocytes (FCM), two
      target cells in vivo, was compared with that in PK-15 cells. Cultures were
      inoculated with either the postweaning multisystemic wasting syndrome (PMWS)
      associated strain Stoon-1010 or the abortion-associated strain 1121. Viral
      proteins were visualized and virus production was determined. In PK-15 cells, the
      capsid protein was expressed between 6 and 12 hours post inoculation (hpi), it
      relocated to the nucleus between 12 and 24 hpi. At that time, Rep protein was
      also detected in the nucleus. This sequence of events also occurred in FCM and
      PAM but nuclear localized antigens appeared later (48 hpi) and in a lower
      percentage of cells. In PAM, clear differences in susceptibility were seen
      between pigs. In PAM from two out of five tested pigs, nuclear localized antigens
      were not detected, whereas in PAM from three other pigs they were seen in up to
      20% of the antigen-positive cells. Virus production was observed in PK-15 but not
      in PAM or FCM cultures. In a second study, the replication kinetics of seven
      different PCV2 strains were compared in PK-15 cells. It was shown that the two
      abortion-associated strains had a different replication kinetics in comparison
      with PMWS or porcine dermatitis and nephropathy syndrome associated strains. With
      the abortion-associated strains, a higher number of infected cells was observed
      at 24 hpi and the percentage of infected cells with nuclear localised antigens
      was lower compared to that of other strains.

PMID- 15578239
TI  - The complete sequence of the genomic RNA of an isolate of Lily virus X (genus
      Potexvirus).
AB  - The complete sequence of the genomic RNA of an isolate of Lily virus X (LVX) has
      been determined for the first time. The isolate from the Netherlands was 5823
      nucleotide (nt) long excluding the 3'-poly(A) tail, making it the shortest
      reported potexvirus sequence. The 5'-non-coding region begins with GGAAAA like
      that of Scallion virus X (ScaVX) and some isolates of Cymbidium mosaic virus
      (CymMV), whereas those of other sequenced potexviruses probably all begin with
      GAAAA. The genome organisation was similar to that of other members of the genus
      except that a TGBp3-like region lacked a normal AUG start codon. A phylogenetic
      analysis based on the entire coding sequence showed that LVX was most closely
      related to Strawberry mild yellow edge virus and belonged in a subgroup of the
      genus that also contains CymMV, Narcissus mosaic virus, ScaVX, Pepino mosaic
      virus, Potato aucuba mosaic virus and White clover mosaic virus.

PMID- 15578240
TI  - Detection of a novel border disease virus subgroup in Tunisian sheep.
AB  - Nine pestiviruses isolated from different batches of a contaminated Tunisian
      sheep pox vaccine and one Tunisian field ovine isolate of border disease virus
      (BDV) were studied at the antigenic and molecular levels. Seroneutralization
      tests were carried out on three vaccine isolates, the Tunisian field isolate and
      representative reference strains of the different pestivirus groups. The
      antigenic study showed that the Tunisian isolates were closer to the two BDV
      reference strains than to the Alfort-187 and the NADL reference strains.
      Comparison of the nucleotide sequences of the 5'-non coding regions of all the
      Tunisian isolates to those of other pestiviruses have shown that these isolates
      were distinct from the established pestivirus species. The entire N(pro)-E2
      coding sequences of four Tunisian isolates were determined and compared to other
      pestiviruses. Segregation of these pestiviruses based on the N(pro)-E2 region was
      identical to that obtained with the 5'UTR sequences. The phylogenetic tree
      obtained with these sequences showed that the Tunisian isolates formed a separate
      branch between the BDV and CSFV groups, and consequently a possible new species
      within the pestivirus genus. However, as indicated by the antigenic study and the
      host origin of the isolates, the Tunisian isolates were assigned to a novel
      subgroup within the BDV species.

PMID- 15578241
TI  - Characterization of the active site and insight into the binding mode of the anti
      angiogenesis agent fumagillin to the manganese(II)-loaded methionyl
      aminopeptidase from Escherichia coli.
AB  - EPR spectra were recorded for methionine aminopeptidase from Escherichia coli
      (EcMetAP-I) samples (approximately 2.5 mM) to which one and two equivalents of
      Mn(II) were added (the latter is referred to as [MnMn(EcMetAP-I)]). The spectra
      for each sample were indistinguishable except that the spectrum of [MnMn(EcMetAP
      I)] was twice as intense. The EPR spectrum of [MnMn(EcMetAP-I)] exhibited the
      characteristic six-line g approximately 2 EPR signal of mononuclear Mn(II) with
      A(av)((55)Mn)=9.3 mT (93 G) and exhibited Curie-law temperature dependence. This
      signal is typical of Mn(II) in a ligand sphere comprising oxygen and/or nitrogen
      atoms. Other features in the spectrum were observed only as the temperature was
      raised from that of liquid helium. The temperature dependences of these features
      are consistent with their assignment to excited state transitions in the S=1, 2
      ... 5 non-Kramer's doublets, due to two antiferromagnetically coupled Mn(II) ions
      with an S=0 ground state. This assignment is supported by the observation of a
      characteristic 4.5 mT hyperfine pattern, and by the presence of signals in the
      parallel mode consistent with a non-Kramers' spin ladder. Upon the addition of
      the anti-angiogenesis agent fumagillin to [MnMn(EcMetAP-I)], very small changes
      were observed in the EPR spectrum. MALDI-TOF mass spectrometry indicated that
      fumagillin was, however, covalently coordinated to EcMetAP-I. Therefore, the
      inhibitory action of this anti-angiogenesis agent on EcMetAP-I appears to involve
      covalent binding to a polypeptide component at or near the active site rather
      than direct binding to the metal ions.

PMID- 15578242
TI  - The metal bonding domain of the antitumor drug Fe(II)-bleomycin: a DFT
      investigation.
AB  - The geometric and electronic structure of ferrous complexes of bleomycin
      (Fe(II)BLM) has been investigated by means of density functional theory (DFT)
      calculations. The active site of this antitumor drug is a highly distorted
      octahedral complex, with the coordination sphere completed by the five known
      endogenous ligands, including pyrimidine, imidazole, deprotonated amide, and
      secondary and primary amines. We have addressed the controversial issue of the
      nature of the sixth axial ligand, which we have identified as the oxygen of the
      carbamoyl group. Our conclusions are further validated by a comparison with
      structural data derived from NMR experiments. Moreover, because of the high
      sensitivity of structural data on the pH of the environment, we have investigated
      the effect of a different protonation state of the histidine amide on the
      geometric structure of the Fe(II)BLM complex. The extensive model of the active
      site of bleomycin considered in this work allows us to check the limitations of
      previous investigations based on simplified models.

PMID- 15578243
TI  - Simultaneous repair of bilateral groin hernias using local anaesthesia: a review
      of 199 cases with a five-year follow-up.
AB  - BACKGROUND: There has been controversy concerning the simultaneous repair of
      bilateral groin hernias and the method of anaesthesia. METHODS: A consecutive
      series of 199 bilateral inguinal hernias was repaired by the Lichtenstein non
      tension mesh technique over a two-year period (1997-98). In 96% of them local
      anaesthesia was used. These were reviewed after five years. RESULTS: There were
      no increased recurrence or infection rates, with both between 0.5-1%. Pulmonary
      and urinary complications did not occur. The cost of this technique is
      substantially less than sequential or laparoscopic operations. DISCUSSION: The
      reasons advanced for sequential repair of bilateral hernias have been the lower
      risks of infection and recurrence. Neither of these fears is evident from this
      study. Furthermore, the use of local anaesthesia permits the operation to be done
      in a day care clinic. CONCLUSIONS: Simultaneous bilateral repair of inguinal
      hernias using local anaesthesia is as effective as sequential repair, at lower
      cost and with less total time off work.

PMID- 15578244
TI  - Usher's Selvage.

PMID- 15578245
TI  - Intraperitoneal treatment of incisional and umbilical hernias using an innovative
      composite mesh: four-year results of a prospective multicenter clinical trial.
AB  - Intraperitoneal positioning of conventional parietal mesh provides efficient
      reconstruction but causes visceral adhesion formation in 80-100% of the cases.
      The purpose of this clinical trial was to assess the performance and tolerance of
      a new generation of polyester mesh protected by a hydrophilic resorbable film.
      Eighty patients were included in a prospective multicenter clinical trial.
      Patients were treated for ventral hernia via an open approach (64%) or
      laparoscopically (36%). All meshes were implanted in a midline intraperitoneal
      location. The main objective was to evaluate the anti-adhesive capability of the
      mesh in relation to the viscera. In order to assess the absence of visceral
      adhesion objectively, an ultrasound (US) specific examination was initially
      validated (pre-operative prediction vs. per-operative findings) and then used
      during the follow-up. The usual clinical parameters were also collected to follow
      the patients on a period up to 4 years. Pre-operative US prediction vs. per
      operative macroscopic findings: sensitivity 79%, overall accuracy 76%, negative
      predictive value 85%. After 12 months, 86% of the patients were ultrasonically
      adhesion free. Early post-operative complications were: seroma/hematoma (16%),
      subcutaneous infection (4%), cutaneous necrosis (1%) and occlusions (outside the
      mesh) (2.5%). No mortality was reported. Clinically, after 12-month follow-up, no
      complication related to post-operative adhesions to the mesh was noted:
      (occlusion 0%, fistula 0%). Late complications were: mesh sepsis (1%), new
      defects (4%) and recurrence (2.5%). Finally, 56 patients (75.7%) were clinically
      evaluated with a mean follow-up of 48+/-6 months. One direct recurrence was noted
      while six patients experienced new defect outside the mesh. No long-term severe
      complication such as occlusion or enterocutaneous fistula was observed. Based on
      a mean clinical follow-up of 4 years, the results of this prospective multicenter
      clinical trial demonstrate the safety and the efficiency of this composite mesh
      in the intraperitoneal treatment of incisional and umbilical hernia. In
      particular there was no early or long-term main complication due to the
      intraperitoneal location of the mesh.

PMID- 15578246
TI  - Is short-term efficacy of locally injected corticosteroids now an established
      fact?

PMID- 15578247
TI  - Churg-Strauss syndrome and the leukotriene receptor antagonist pranlukast.
AB  - The authors studied eight cases of Churg-Strauss syndrome (CSS) associated with
      the use of pranlukast, a common cysteinyl leukotriene receptor antagonist (LTRA)
      in Japan. The patients who received pranlukast showed significantly increased
      peripheral blood eosinophil count, neurological disability scores, and poor
      responses to corticosteroid in comparison with those patients not receiving
      pranlukast. We suggest that preceding administration of pranlukast aggravates
      clinical presentations of CSS.

PMID- 15578248
TI  - P-ANCA cranial pachymeningitis: a case report.
AB  - Pachymeningitis is an inflammatory process that thickens the dura mater. This
      disease has various etiologies including infectious, neoplastic, or autoimmune
      diseases. We present the case of a patient who developed cranial pachymeningitis
      with a clinical and biological picture suggestive of a neurological form of
      vasculitis. A 51-year-old woman developed rhinitis, otitis media, headaches, and
      deterioration of her condition after a course of recombinant hepatitis B vaccine.
      After a booster dose of the vaccine, she developed unilateral visual loss and
      impairment of multiple cranial nerves. Blood analysis showed inflammation and
      presence of antimyeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA).
      Cranial magnetic resonance imaging (MRI) showed pachymeningitis. A complete
      remission was obtained with immunosuppressive therapy. The initial clinical
      presentation and subsequent remission under immunosuppressive therapy were
      suggestive of a vasculitis with nervous system involvement. Though vasculitis was
      not proven histologically in this patient, we believe that MPO-ANCA-related
      autoimmunity provoked the patient's disease as already reported in similar cases.
      As pachymeningitis is a fibrosing process, early recognition and treatment of an
      autoimmune etiology, even in the absence of previous pulmonary or renal
      involvement, is required to prevent definitive neurological impairment.

PMID- 15578249
TI  - Trends in Shigella outbreaks in the Israeli military over 15 years.

PMID- 15578250
TI  - Comparison of endoscopic procedures vs Lichtenstein and other open mesh
      techniques for inguinal hernia repair: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: For the scientific evaluation of the endoscopic and open mesh
      techniques for the repair of inguinal hernia, meta-analyses of randomized
      controlled trials (RCT) are necessary. The Lichtenstein repair is one of the most
      common open mesh techniques and therefore of special interest. METHODS: After an
      extensive search of the literature and a quality assessment, a total of 34 RCT
      comparing endoscopic procedures both transabdominal preperitoneal (TAPP) and
      total extraperitoneal (TEP)--with various open mesh repairs were deemed to be
      suitable for a formal meta-analysis of the relevant parameters. These studies
      included data for 7,223 patients. Trials that used the Lichtenstein repair for
      the control group (23 of 34 trials) were analyzed-separately. RESULTS:
      Significant advantages for the endoscopic procedures compared with the
      Lichtenstein repair include a lower incidence of wound infection (Peto odds
      ratio, 0.39; 95% confidence interval, 0.26, 0.61), a reduction in hematoma
      formation (0.69 [0.54, 0.90]) and nerve injury (0.46 [0.35, 0.61]), an earlier
      return to normal activities or work (-1.35[-1.72, -0.97]), and fewer incidences
      of chronic pain syndrome (0.56[0.44, 0.70]). No difference was found in total
      morbidity or in the incidence of intestinal lesions, urinary bladder lesions,
      major vascular lesions, urinary retention and testicular problems. Significant
      advantages for the Lichtenstein repair include in a shorter operating time
      (5.45[1.18, 9.73]), a lower incidence of seroma formation (1.42[1.13, 1.79]), and
      fewer hernia recurrences (2.00[1.46, 2.74]). Similar results are seen when
      endoscopic procedures are compared with other open mesh repairs. However, in this
      comparison, total morbidity was lower with the endoscopic operations (0.73[0.61,
      0.89]). The incidence of seroma formation, chronic pain syndromes, and hernia
      recurrence was not significantly different. CONCLUSION: Endoscopic repairs do
      have advantages interms of local complications and pain-associated parameters.
      For more detailed evaluation further well-structured trials with improved
      standardization of hernia type, operative technique, and surgeons' experience are
      necessary.

PMID- 15578251
TI  - The value of imaging techniques in the staging of pancreatic cancer.
AB  - BACKGROUND: The aim of this study was to assess the clinical value of endoscopic
      ultrasound (EUS) in the staging of pancreatic carcinoma and to compare it to
      ultrasonography (US) and CT. METHODS: We evaluated 45 patients (21 women and 24
      men with a mean age of 62.1 years) who had undergone surgical treatment for
      pancreatic cancer between 1994 and 2004. Out analysis focused on the overall
      accuracy, sensitivity, and specificity of routine and Doppler US, CT, and EUS.
      RESULTS: Endoscopic ultrasound was the most accurate modality for local tumor
      staging (93.1%), vascular infiltration (90%), and lymph node assessment (87.5%).
      Routine US was the least accurate (82.5%, 67.5%, and 72.5%, respectively). The
      accuracy rates for CT and Doppler US were similar (88.1%, 82.5% and 80.0%,
      respectively). CONCLUSIONS: Endoscopic ultrasound is the most accurate method
      available to stage pancreatic cancer in the preoperative period. However, the
      advantage of EUS over CT and US does not justify its routine use due to its high
      cost, low availability, and invasiveness.

PMID- 15578252
TI  - [Cooperation between physician and pharmacist to determine and resolve errors in
      concomitant medication previously prescribed for trauma patients. Quality
      assurance study].
AB  - The problems to be resolved were to develop identification schemes for erroneous
      long-term medication of newly admitted trauma patients, to detect the nature of
      medication errors and their frequency of occurrence, to demonstrate the effects
      by therapy corrections, and to ensure the continuation of optimized prescription
      after discharge. Upon admission of new trauma surgery patients their current
      prescriptions are compiled and converted to formulary if possible as well as
      looked over for medication errors. This procedure is accompanied by an evaluation
      of the latter.In consequence, the surgeon is able to concentrate on optimizing
      the current medication to prevent subsequent errors and serious complications.To
      improve the acceptance of the corrected prescription, patients are advised on
      their discharge by the pharmacist also. The general practitioners of the patients
      are informed by an additional pharmacy report concerning sustained medication.A
      correction of medication errors was necessary in 6.17% of the controlled long
      term prescriptions and 20.22% of the controlled 4944 patients. The most common
      problems were dosage errors; the most serious errors were neglected interactions
      and side effects. By better cooperation of surgeon and pharmacist we can improve
      the quality of pharmacotherapy of our patients. The correction of long-term
      prescriptions provides support and better information to the surgeon. Direct and
      indirect expenses can be reduced.

PMID- 15578253
TI  - [Marburg shoulder radiography splint (MSR splint) for standardized and high
      quality plain film radiography in fractures of the proximal humerus].
AB  - To ensure safe, quick, pain-relieving, standardized, and reproducible high
      quality plain film radiography in fractures of the proximal humerus, the MSR
      splint was introduced into clinical practice. With the rectangular and completely
      radiolucent splint the shoulder radiographs are obtained in supine position by a
      sole radiographer. Two radiographs are taken in projection at 90 degrees to one
      another: the true anteroposterior and axillary views, the most important views
      for fracture visualization and assessment. The smooth flat bottom part of the
      splint glides easily across the X-ray table below the injured shoulder. The arm
      lying on the chest is carefully rotated externally up to the neutral position and
      placed in the splint, then fixed with Velcro fastening with the forearm
      supinated. The splint is adjusted to the patient for the anteroposterior view
      which is taken with the central ray directed at the coracoid process and
      perpendicularly on the film cassette. For the axillary view the MSR splint
      holding the upper extremity is carefully swiveled into a 80-90 degrees abduction
      position. Even in cases of comminuted fractures this maneuver is not painful for
      the patients. The X-ray tube is put into a horizontal position with the central
      ray pointing to the humeral head in an angle about 25 degrees to the long body
      axis. The cassette is placed upright in touch with the shoulder girdle. In our
      institution the MSR splint is not only routinely used for diagnosing fractures of
      the proximal humerus but also for radiological follow-up controls.

PMID- 15578254
TI  - [New technologies in tissue engineering. Visions of an unlimited bone generation
      without problems].

PMID- 15578255
TI  - [Allogenic transplantation of human mesenchymal stem cells for tissue engineering
      purposes: an in vitro study].
AB  - Due to their plasticity and high proliferation capacity in vitro, human
      mesenchymal stem cells (MSC) are promising candidates for tissue engineering
      approaches of mesenchymal tissues like bone, cartilage, or tendon.
      Undifferentiated MSC do not express immunologically relevant cell surface
      markers. They inhibit the proliferation of allogeneic T-cells in vitro and elicit
      no immune response after allogeneic or xenogenic transplantation. Thus, MSC ought
      to be seen as immunoprivileged or immunomodulating cells. Here, we characterize
      the immune status and -behavior of MSC and MSC-derived osteogenic precursors in
      order to evaluate the usefulness of allogeneic MSC for tissue engineering of
      bone. Human MSC were isolated from bone marrow of hematologically normal
      voluntary donors. Osteogenic differentiation was induced by adding dexamethasone,
      ascorbic acid and beta-glycerophosphate. After 0, 8, 16 and 24 days, MSC were co
      cultivated with allogeneic mononuclear cells. In parallel, the expression of
      immunologically relevant cell surface markers was monitored by flow cytometry.
      Undifferentiated and differentiated MSC did not stimulate allogeneic lymphocytes.
      MSC were negative for MHC-II, CD40, CD40L, CD80 (B7-1) and CD86 (B7-2), positive
      for MHC-I, and kept this expression pattern during osteogenic differentiation.
      Our results support the hypothesis that MSC are immunoprivileged cells which are
      potentially at disposal for HLA-incompatible cell replacement therapies.

PMID- 15578256
TI  - [Effects of mechanical strain on human osteoblastic precursor cells in type I
      collagen matrices].
AB  - BACKGROUND: The aim of the present study was to investigate the effect of
      mechanical strain on human osteoblastic precursor cells in a three-dimensional
      scaffold. METHODS: Osteoblastic precursor cells were seeded in a collagen type I
      gel and mechanically stretched by daily application of cyclic uniaxial strain.
      The expression of histone H4, core binding factor 1, alkaline phosphatase,
      osteopontin, osteocalcin, and collagen type I was investigated by analysing the
      mRNA. Cell and matrix orientation were investigated by scanning electron
      microscopy. RESULTS: Cyclic stretching increased cell proliferation. The
      expression of osteogenic markers was slightly increased by mechanical strain. The
      cells and matrix were strictly oriented in the stress direction. CONCLUSION: The
      application of mechanical load might have a beneficial effect on the quality and
      quantity of generated bone tissue and might be a important factor in tissue
      engineering of bone.

PMID- 15578257
TI  - The kgmB gene, encoding ribosomal RNA methylase from Streptomyces tenebrarius, is
      autogenously regulated.
AB  - The KgmB methylase (the kanamycin-gentamicin resistance methylase from
      Streptomyces tenebrarius) acts at G-1405 of 16S rRNA within the sequence CGUCA
      that is also found 6 bp in front of ribosomal binding site of the kgmB gene. The
      kgmBColon, two colonslacZ gene and operon fusions were used in order to test for
      translational autoregulation of kgmB gene. Overexpression of kgmB either in cis
      or in trans drastically decreased the level of expression of the fusion protein.
      However, mutagenesis eliminated any role for the CGUCA sequence in translational
      autoregulation. Hence, the role of second putative regulatory sequence (CGCCC)
      that was shown to be involved in regulation of another methylase, Sgm (sisomicin
      gentamicin methylase gene from Micromonospora zionensis) was examined. It was
      shown that the Sgm methylase can also decrease the level of expression of the
      kgmBColon, two colonslacZ fusion protein.

PMID- 15578258
TI  - Drug-induced stimulation and suppression of action monitoring in healthy
      volunteers.
AB  - RATIONALE: Action monitoring has been studied extensively by means of measuring
      the error-related negativity (ERN). The ERN is an event-related potential (ERP)
      elicited immediately after an erroneous response and is thought to originate in
      the anterior cingulate cortex (ACC). Although the ACC has a central role in the
      brain, only a few studies have been performed to investigate directly the effects
      of drugs on action monitoring. A recent theory argues that the mesencephalic
      dopamine system carries an error signal to the ACC, where it generates the ERN.
      METHODS: ERPs and behavioral measurements were obtained from 12 healthy
      volunteers performing an Eriksen Flankers task. On each of the 4 test days, the
      stimulant D-amphetamine, the sedative lorazepam, the antidepressant mirtazapine,
      or a placebo was orally administered in a double-blind, four-way crossover
      design. RESULTS: The indirect dopamine agonist amphetamine led to a strong
      enlargement of ERN amplitudes without affecting reaction times. Lorazepam and
      mirtazapine both showed slowing of responses, but only lorazepam led to reduced
      ERN amplitudes. CONCLUSIONS: Administration of amphetamine leads to stimulated
      action monitoring, reflected in increased ERN amplitudes. This result provides
      evidence for dopaminergic involvement in action monitoring and is in line with
      differences in ERN amplitude found in neuropsychiatric disorders also suggesting
      dopaminergic involvement. The different effects for lorazepam and mirtazapine are
      probably caused by the neurobiological characteristics of these two types of
      sedation. Action monitoring is suppressed after administration of lorazepam,
      because the GABAergic pathways directly inhibit ACC functioning, whereas the
      histaminergic pathways of mirtazapine do not innervate the ACC directly.

PMID- 15578260
TI  - Dynamics of learning and transfer of muscular and spatial relative phase in
      bimanual coordination: evidence for abstract directional codes.
AB  - The present study addressed whether the timing of muscle activation and the
      relative direction of limb movements are dissociable constraints that may affect
      learning and transfer of bimanual coordination patterns, either independently or
      in combination. Subjects were assigned to two experimental groups in which the to
      be-learned muscular phasing (135 degrees ) was either practiced with 45 degrees
      (i.e., predominantly isodirectional) or 135 degrees (i.e., predominantly
      nonisodirectional) of spatial relative phase (RP) across 2 days of practice.
      Prior to, during, and following practice, probe tests were held in which various
      relative phasing patterns were administered to assess transfer of learning.
      Converging evidence was obtained that the relative direction of moving limbs
      prominently constrained transfer of learning rather than muscular relationships.
      Acquisition of a specific pattern resulted in spontaneous positive transfer of
      learning to a new coordination pattern having the same spatial RP but not to a
      pattern with a different spatial RP, irrespective of muscular phasing
      relationships. In summary, the present results suggest that learning and transfer
      of coordination patterns is mediated by abstract directional codes that become
      part of the memory representation for bimanual coordination.

PMID- 15578261
TI  - The HLA-G*0105N null allele induces cell surface expression of HLA-E molecule and
      promotes CD94/NKG2A-mediated recognition in JAR choriocarcinoma cell line.
AB  - HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast
      cells, and is thought to play a key role in the induction of materno-fetal
      tolerance during pregnancy. In addition, the HLA-G gene provides a suitable
      leader sequence peptide capable of binding to HLA-E. However, the existence of
      placentas homozygous for the HLA-G*0105N null allele suggests that HLA-G1 might
      not be essential for fetal survival. To investigate whether expression of the HLA
      G*0105N allele supports HLA-E cell surface expression, we transfected the HLA
      G*0105N gene into JAR trophoblast cells. Flow cytometry analysis showed that HLA
      G*0105N-transfected cells express surface HLA-E to a similar extent as the
      unmutated HLA-G gene, whereas HLA-G1 cell surface expression was undetectable.
      Using the NKL cell line in a standard (51)Cr release assay, the HLA-E molecules
      were found to inhibit natural killer lysis, through a mechanism partially
      dependent on CD94/NKG2A-mediated recognition.

PMID- 15578262
TI  - Limited impact of multiple 5' single-nucleotide polymorphisms on the
      transcriptional control of the human beta 2-adrenoceptor gene.
AB  - The human beta(2)-adrenoceptor (beta(2)-AR) is subject to agonist-induced down
      regulation. The degree of down-regulation is associated with certain single
      nucleotide polymorphisms (SNPs) through yet unknown mechanisms. The 5'-leader
      sequence of the beta(2)-AR gene contains several SNPs that are in strong linkage
      disequilibrium. The -367 T/C polymorphism, in particular, has been shown to
      affect transcriptional activity in reporter gene assays. In the present study we
      analysed the impact of this -367 SNP on the transcription rate of the beta(2)-AR
      gene in the context of the complete natural locus. Taking advantage of the
      additional full disequilibrium with the +79 SNP in the beta(2)-AR coding
      sequence, allele-specific transcript quantification was performed in PBMCs of six
      -367 heterozygous mild asthmatic patients. Our data are in line with the reported
      impact of the -367 SNP and give no indication of additional haplotype-related
      effects on beta(2)-AR transcription. We further show that the -367 SNP affects
      the binding of a yet unidentified transcription factor complex, whose binding
      activity is not modulated by pharmacological compounds that induce or down
      regulate beta(2)-AR expression, suggesting a role in constitutive steady state
      expression rather than in inducible expression. As the beta(2)-AR allele with a
      higher transcription rate associates with stronger agonist-induced down
      regulation, it is not likely that the -367 SNP is causally related to the degree
      of down-regulation.

PMID- 15578263
TI  - Molecular cloning and expression of two chicken invariant chain isoforms produced
      by alternative splicing.
AB  - The biosynthesis of distinct forms of the invariant chain (Ii) protein from a
      unique gene as the result of differential splicing patterns has been observed in
      humans and mice. However, there have been no reports on the existence of Ii
      isoforms in avian species. In the present study, we identified two chicken Ii
      cDNAs by RT-PCR and RACE, and examined the Ii gene copy number, mRNA expression
      and protein expression by Southern blotting, Northern blotting and
      immunofluorescence confocal microscopy, respectively. One of the Ii cDNAs, named
      Ii-1, was 1,151 bp in length, and had an open reading frame (ORF) of 672
      nucleotides, in agreement with a previously identified chicken Ii sequence; the
      other, named Ii-2, was 1,337 bp long and had an ORF of 861 nucleotides. Southern
      blotting confirmed that these cDNAs were derived from a single copy gene.
      Northern blotting performed with total RNA from various tissues of 6-week-old
      chickens revealed high levels of Ii-1 and Ii-2 mRNA expression in the spleen and
      bursa of Fabricius, and low levels of Ii-1 expression in the thymus, heart and
      liver, while Ii-2 was not expressed in these tissues. High levels of expression
      of both Ii isoforms were detected in the spleen and bursa of Fabricius during
      late embryogenesis. Immunofluorescence staining showed that Ii proteins were
      expressed in the cell membranes of the splenocytes. These data suggest that
      chicken Ii exists in two isoforms resulting from alternative splicing, and is
      strongly expressed in the major immune organs.

PMID- 15578265
TI  - Genetic analysis of Toll/Interleukin-1 Receptor (TIR) domain sequences from
      rhesus macaque Toll-like receptors (TLRs) 1-10 reveals high homology to human
      TLR/TIR sequences.
AB  - Toll-like receptors (TLRs) form a major group of pattern recognition receptors of
      the innate immune system that sense molecular patterns on microbes. The
      cytoplasmic Toll/Interleukin-1 Receptor (TIR) signaling domain is instrumental in
      inducing a signaling cascade upon recognition of specific ligands by TLRs.
      Because nonhuman primates are used as models of infectious and immune processes,
      we sought to obtain an increased understanding of nonhuman primate TLRs. We
      obtained the nucleotide sequences of the TIR domains of rhesus macaque TLRs 1-10
      and examined their genetic relationships to TLRs from humans and mice. Alignment
      of the deduced amino acid sequences revealed macaque-specific changes mostly
      outside the conserved "Box" regions of the TLR/TIR domain. Assessment of
      mutational biases among TLRs from multiple species revealed a strong overall bias
      towards synonymous substitutions, with a few short regions showing evidence for
      positive selection outside the Box regions. This first presentation of the
      TLR/TIR domain sequences from nonhuman primates indicates that although there are
      species-specific differences, a high level of sequence homology exists in the
      critical signaling Box regions of macaque, human, and murine TLR/TIR domains.
      These findings suggest that animal models, including nonhuman primates, will be
      useful in modeling human TLR pathophysiology and therapy.

PMID- 15578264
TI  - Potential regulatory sequences in the untranslated regions of the baboon MHC
      class Ib gene, Paan-AG, more closely resemble those in the human MHC class Ia
      genes than those in the class Ib gene, HLA-G.
AB  - The baboon major histocompatibility complex (MHC) class Ib gene, Paan-AG, is
      structurally similar to the human MHC class Ia gene, HLA-A, but exhibits
      characteristics similar to those of the class Ib gene HLA-G. These include
      limited polymorphism, alternative splicing of a single message, and restricted
      tissue distribution, with high expression in the placenta. In order to determine
      whether regulatory elements controlling expression of Paan-AG resemble those of
      HLA-A or HLA-G, we cloned the 5' and 3' untranslated regions of Paan-AG.
      Unexpectedly, sequence comparisons showed that potential regulatory elements in
      Paan-AG strikingly resembled those in HLA-A and differed in major respects from
      those in HLA-G. Unlike HLA-G, Paan-AG contained an intact interferon-gamma
      stimulated response element (ISRE) in the promoter. Studies using luciferase
      reporter assays showed that the Paan-AG ISRE was functional. The basal activity
      of the Paan-AG ISRE and its response to interferon-gamma was similar to that of
      class Ia MHC genes. Further, we identified an ISRE in the 3' untranslated region
      of Paan-AG that is known to be functional in HLA-A2 but is deleted in HLA-G.
      These experiments predict that functional studies may demonstrate differences in
      regulation of expression of Paan-AG and HLA-G genes, which could restrict the use
      of the baboon as a primate model for studying HLA-G expression and function.

PMID- 15578266
TI  - The EGF-TM7 family of the rat.
AB  - EGF-TM7 receptors are adhesion class heptahelical molecules predominantly
      expressed by cells of the immune system. Based on an analysis of the recently
      unraveled genome, the EGF-TM7 family of the rat is described here. Like the
      mouse, the rat has three EGF-TM7 receptors--CD97, EMR1 and EMR4. The highest
      conservation between the orthologues lies within the membrane-spanning part and
      emphasizes the functional importance of this region.

PMID- 15578268
TI  - Vascular adhesion and transendothelial migration of eosinophil leukocytes.
AB  - Tissues respond to injury with inflammation in an effort to protect and repair
      the damaged site. During inflammation, leukocytes typically accumulate in
      response to certain chemicals produced within the tissue itself. The passage of
      leukocytes through the vascular lumen into tissues occurs in several phases,
      including rolling, activation, firm adhesion, transendothelial migration, and
      subendothelial migration. Although infiltration of eosinophil leukocytes is one
      of the most important aspects of allergic inflammatory reactions, eosinophils
      also participate in nonallergic inflammation. Eosinophil accumulation is
      regulated not only by endothelial adhesion molecules, but also by interactions
      between eosinophil adhesion molecules and extracellular matrix elements. This
      review summarizes the regulation of eosinophil leukocyte adhesion and migration.
      A better understanding of eosinophil recruitment responses may lead to the
      development of novel therapeutics for chronic allergic diseases.

PMID- 15578269
TI  - L-aspartate-immunoreactive neurons in the rat enteric nervous system.
AB  - L-aspartate (L-Asp) is an excitatory neurotransmitter in the central nervous
      system. In the present study, we demonstrate, for the first time, the presence of
      L-Asp in a particular neuronal cell class in the enteric nervous system (ENS).
      Scattered L-Asp-immunoreactive neuronal cell bodies and nerve fibers were found
      extensively in both the myenteric and submucosal plexus throughout the small and
      large intestines. Many L-Asp-immunoreactive nerve fibers, which originated from
      intrinsic nerve cell bodies, were found in the ganglia and interconnecting nerve
      bundles. Electron microscopy revealed that L-Asp-immunoreactive terminals
      frequently formed synaptic contacts with intrinsic nerve cells, suggesting that
      some L-Asp-immunoreactive neurons might function as interneurons. These results
      suggest that L-Asp-immunoreactive neurons play a significant role within the ENS
      to control intestinal functions. The presence of enteric L-Asp-immunoreactive
      neurons provides strong support for the proposal that L-Asp is a neuromodulator
      in the rat ENS.

PMID- 15578267
TI  - The bile salt export pump: molecular properties, function and regulation.
AB  - Secretion of bile salts from the hepatocyte into bile is the major driving force
      for the generation of bile flow. Identification of the bile salt export pump
      (BSEP, ABCB11) as the main adenosine-triphosphate-dependent bile salt transporter
      in mammalian liver has led to a greater understanding of the biliary bile salt
      secretory process and its regulation. The biology and pathobiology of BSEP have
      been the subject of many recent studies. Thus, it has been recognized that while
      mutations in the gene encoding BSEP are responsible for a subgroup of progressive
      familial cholestasis (progressive familial intrahepatic cholestasis subtype 2), a
      pediatric cholestatic disorder that may progress to cirrhosis, defective
      expression or function of BSEP may underlie some forms of drug-induced
      cholestasis. The present review summarizes recent data on the molecular
      properties and regulation of BSEP, as well as the clinical implications of absent
      or defective function of this hepatic efflux pump.

PMID- 15578270
TI  - Increased noise sensitivity and altered inner ear MENA distribution in VASP-/-
      mice.
AB  - Vasodilator-stimulated phosphoprotein (VASP) and mammalian-enabled protein (MENA)
      share similar cellular localisation and functions (signal transduction pathways,
      regulation of actin cytoskeleton dynamics). Functional substitution and
      compensation among Ena/VASP proteins have been proposed as the reason for the
      absence of major morphological and functional deficits in VASP-/- mice. The aim
      of this study was to investigate VASP expression in the mouse cochlea, to analyse
      cochlear function in VASP-/- mice compared with wildtype mice, and to analyse
      cochlear MENA distribution taking into account that MENA protein might compensate
      VASP loss in the cochlea of VASP-/- mice. We confirmed specific VASP expression
      in the pillar cells of the mice organ of Corti as previously reported for rat
      cochlea. By analysing the hearing function in VASP-/- mice, we found no
      differences in auditory brainstem responses and distortion product otoacoustic
      emissions from those of wildtype mice but evidence for an increased noise
      sensitivity at lower frequencies. When MENA protein levels in cochlea tissue were
      tested in mutant and wildtype mice by Western blot analysis, no significant
      differences were found, as was also seen with regard to MENA mRNA levels in laser
      microdissected single pillar cells. Most surprisingly, however, MENA protein was
      absent in pillar cells of VASP-/- mice, whereas it was detected in other cochlear
      cells. The finding of a cell-specific, and not organ-specific, redundancy of MENA
      protein expression noted for the first time in VASP-/- mice is proposed as the
      reason for the observed distinct cochlear phenotype.

PMID- 15578271
TI  - Human embryonic germ cells isolation from early stages of post-implantation
      embryos.
AB  - Human embryonic germ (hEG) cell is a very important alternative pluripotent stem
      cell resource. We describe the derivation of hEG cells from human embryonic fetal
      gonads over 6-8 weeks postconception. A large number of EG-like cell clumps were
      obtained at passage 1 and thus facilitated the following routine culture when the
      donor tissues were trypsinized with gentle pipetting and plated on feeder layer
      cells in the initial culture. Eight diploid hEG cell lines have been cultivated
      in vitro for extended periods while maintaining expression of markers
      characteristic of pluripotent stem cells. Human EG cells expressed transcription
      factor Oct4, a marker of pluripotency in mouse EG cells, at a high and steady
      level. Expression of markers indicative of differentiation along the three germ
      lineages was also observed in EBs. High level of alkaline phosphatase activity
      was shown in EG cells. These encouraging findings provide a starting point for
      potential applicability of hEG cells.

PMID- 15578272
TI  - Immunocytochemical analysis of cubilin-mediated endocytosis of high density
      lipoproteins (HDL) in epithelial cells of the rat visceral yolk sac.
AB  - Cubilin was recently shown to function as an endocytic receptor for high density
      lipoprotein (HDL) holoparticles and apolipoprotein A-I (apo A-I), the main
      protein constituent of HDL. In the present study, we analyzed the distribution
      and intracellular trafficking of cubilin and HDL in rat visceral yolk sac
      epithelial cells. After epithelial cells were loaded with apolipoprotein E-free
      HDL for 30 min in vitro, double immunofluorescence showed that the apical
      cytoplasm of the cells was strongly stained with anti-cubilin antibodies and anti
      apo A-I/HDL. Furthermore, double immunogold electron-microscopic observations
      revealed the distinct localization of cubilin and HDL in endocytic vacuoles. In
      early endosomes, both were colocalized on the membrane. Although, in late
      endosomes, cubilin was also localized on the membrane, HDL was mainly located in
      the matrix. Both were found in the matrix in lysosomes. In addition, cubilin was
      markedly localized in apical tubules (ATs), which are generally accepted as being
      receptor recycling compartments. Thus, HDL is internalized through cubilin
      mediated endocytosis and is finally transported to lysosomes. By contrast,
      cubilin is mainly translocated to ATs for recycling, although some of the cubilin
      is degraded in lysosomes. Quantitative analysis further revealed that cubilin was
      not concentrated on the membranes of ATs, although it accumulated in the AT area.
      Some HDL were also observed in the AT area. These findings suggest that the
      translocation of cubilin and HDL to ATs from early endosomes occurs through a
      simple sorting mechanism based on the geometry of these compartments and the bulk
      membrane and volume flow.

PMID- 15578273
TI  - Pigment-dispersing hormone (PDH)-immunoreactive neurons form a direct coupling
      pathway between the bilaterally symmetric circadian pacemakers of the cockroach
      Leucophaea maderae.
AB  - Circadian locomotor activity rhythms of the cockroach Leucophaea maderae are
      driven by two bilaterally paired and mutually coupled pacemakers that reside in
      the optic lobes of the brain. Transplantation studies have shown that this
      circadian pacemaker is located in the accessory medulla (AMe), a small neuropil
      of the medulla of the optic lobe. The AMe is densely innervated by about 12
      anterior pigment-dispersing-hormone-immunoreactive (PDH-ir) medulla (PDHMe)
      neurons. PDH-ir neurons are circadian pacemaker candidates in the fruitfly and
      cockroach. A subpopulation of these neurons also appears to connect both optic
      lobes and may constitute at least one of the circadian coupling pathways. To
      determine whether PDHMe neurons directly connect both accessory medullae, we
      injected rhodamine-labeled dextran as neuronal tracer into one AMe and performed
      PDH immunocytochemistry. Double-labeled fibers in the anterior, shell, and
      internodular neuropil of the AMe contralaterally to the injection site showed
      that PDH-ir fibers directly connect both accessory medullae. This connection is
      formed by three anterior PDHMe neurons of each optic lobe, which, thus, fulfill
      morphological criteria for a direct circadian coupling pathway. Our double-label
      studies also showed that all except one of the midbrain projection areas of
      anterior PDHMe neurons were innervated ipsilaterally and contralaterally. Thus,
      anterior PDHMe neurons seem to play multiple roles in generating circadian
      rhythms. They also deliver timing information output and perform mutual pacemaker
      coupling in L. maderae.

PMID- 15578274
TI  - Immunohistochemical distribution of proteins belonging to the receptor-mediated
      and the mitochondrial apoptotic pathways in human placenta during gestation.
AB  - The balance between cell death and cell proliferation and its regulation are
      essential features of many physiological processes and are particularly important
      in fetal morphogenesis and adult tissue homeostasis. Apoptosis is a type of cell
      suicide that is activated in two main ways: through a receptor-mediated pathway
      or through a mitochondrial pathway. We have investigated the immunohistochemical
      distribution of proteins belonging to these two pathways in human placenta during
      gestation by comparing their expression levels between the first and third
      trimester of gestation. In the first trimester, the receptor-mediated pathway
      prevails over the mitochondrial pathway with a moderate/intense expression of its
      three components, viz., Fas ligand (FasL), Fas, and caspase-8, and weak
      positivity of anti-apoptotic FLIP, these proteins being mainly localized in the
      cytotrophoblast compartment. In the third trimester of gestation, there is an
      increased expression of mitochondrial pathway proteins, viz., Apaf-1 and caspase
      9. We have also investigated the expression level of caspase-3, the primary
      effector caspase of both pathways, and have observed that it is moderately
      expressed during gestation, being mainly localized in the cytotrophoblast during
      the first trimester and in both placental compartments during the third trimester
      of gestation. Thus, both pathways actively function in human placenta to execute
      cell death. By means of immunoelectron microscopy, we have further shown that, in
      human placenta, the two proteins of the mitochondrial pathway together with
      caspase-3 are localized both in the cytoplasm and in the nucleus. In particular,
      Apaf-1 and caspase-9 are distributed near to the nuclear envelope suggesting an
      important role for these two proteins in disrupting the nuclear-cytoplasmic
      barrier.

PMID- 15578275
TI  - Expression and distribution of transcription factor CCAAT/enhancer-binding
      protein in the central nervous system of Lymnaea stagnalis.
AB  - The transcription factor, CCAAT/enhancer-binding protein (C/EBP), is involved in
      important physiological processes, such as cellular proliferation and
      differentiation, homeostasis, and higher-order functions of the brain. In the
      present study, we investigated the distribution of mRNA and protein of C/EBP in
      the central nervous system of the pond snail, Lymnaea stagnalis, by in situ
      hybridization and immunohistochemistry. Specificity of the anti-mammalian C/EBP
      antibody against Lymnaea C/EBP (LymC/EBP) was confirmed by combination of sodium
      dodecyl sulfate polyacrylamide gel electrophoresis or isoelectric focusing and
      immunoblotting. Cells positive for in situ hybridization were immunoreactive for
      LymC/EBP in all 11 ganglia. The motoneurons (B1, B2, B4, and B4 clusters) in the
      buccal ganglia and interneurons (cerebral giant cell, CGC) in the cerebral
      ganglia were positive for in situ hybridization and were immunopositive. In the
      pedal ganglion, the right pedal dorsal 1 (RPeD1), pedal A, and pedal C clusters
      exhibited positive signals of in situ hybridization and immunohistochemistry for
      LymC/EBP. CGC and RPeD1 are key neurons for associative learning. In addition,
      the neuropeptidergic cells in the cerebral, pleural, parietal, and visceral
      ganglia were positive for in situ hybridization and immunoreactive.
      Interestingly, although the cytoplasm of almost all immunopositive cells was
      stained, some neuropeptidergic cells located in the light parietal and visceral
      ganglia exhibited immunoreactivity in nuclei. Our results suggest that LymC/EBP
      is involved in learning and memory and in the expression and/or secretion of
      neuropeptides in Lymnaea.

PMID- 15578276
TI  - Trace metal contamination initiates the apparent auto-aggregation, amyloidosis,
      and oligomerization of Alzheimer's Abeta peptides.
AB  - Nucleation-dependent protein aggregation ("seeding") and amyloid fibril-free
      formation of soluble SDS-resistant oligomers ("oligomerization") by hydrophobic
      interaction is an in vitro model thought to propagate beta-amyloid (Abeta)
      deposition, accumulation, and incur neurotoxicity and synaptotoxicity in
      Alzheimer's disease (AD), and other amyloid-associated neurodegenerative
      diseases. However, Abeta is a high-affinity metalloprotein that aggregates in the
      presence of biometals (zinc, copper, and iron), and neocortical Abeta deposition
      is abolished by genetic ablation of synaptic zinc in transgenic mice. We now
      present in vitro evidence that trace (<or=0.8 microM) levels of zinc, copper, and
      iron, present as common contaminants of laboratory buffers and culture media, are
      the actual initiators of the classic Abeta1-42-mediated seeding process and Abeta
      oligomerization. Replicating the experimental conditions of earlier workers, we
      found that the in vitro precipitation and amyloidosis of Abeta1-40 (20 microM)
      initiated by Abeta1-42 (2 microM) were abolished by chelation of trace metal
      contaminants. Further, metal chelation attenuated formation of soluble Abeta
      oligomers from a cell-free culture medium. These data suggest that protein self
      assembly and oligomerization are not spontaneous in this system as previously
      thought, and that there may be an obligatory role for metal ions in initiating
      Abeta amyloidosis and oligomerization.

PMID- 15578278
TI  - [Is the elimination of the internal limiting membrane in macular hole surgery
      both safe and necessary?].

PMID- 15578277
TI  - Studies on the degradation pathway of iron-sulfur centers during unfolding of a
      hyperstable ferredoxin: cluster dissociation, iron release and protein stability.
AB  - The ferredoxin from the thermoacidophile Acidianus ambivalens is a representative
      of the archaeal family of di-cluster [3Fe-4S][4Fe-4S] ferredoxins. Previous
      studies have shown that these ferredoxins are intrinsically very stable and led
      to the suggestion that upon protein unfolding the iron-sulfur clusters degraded
      via linear three-iron sulfur center species, with 610 and 520 nm absorption
      bands, resembling those observed in purple aconitase. In this work, a kinetic and
      spectroscopic investigation on the alkaline chemical denaturation of the protein
      was performed in an attempt to elucidate the degradation pathway of the iron
      sulfur centers in respect to protein unfolding events. For this purpose we
      investigated cluster dissociation, iron release and protein unfolding by
      complementary biophysical techniques. We found that shortly after initial protein
      unfolding, iron release proceeds monophasically at a rate comparable to that of
      cluster degradation, and that no typical EPR features of linear three-iron sulfur
      centers are observed. Further, it was observed that EDTA prevents formation of
      the transient bands and that sulfide significantly enhances its intensity and
      lifetime, even after protein unfolding. Altogether, our data suggest that iron
      sulfides, which are formed from the release of iron and sulfide resulting from
      cluster degradation during protein unfolding in alkaline conditions, are in fact
      responsible for the observed intermediate spectral species, thus disproving the
      hypothesis suggesting the presence of a linear three-iron center intermediate.
      Kinetic studies monitored by visible, fluorescence and UV second-derivative
      spectroscopies have elicited that upon initial perturbation of the tertiary
      structure the iron-sulfur centers start decomposing and that the presence of EDTA
      accelerates the process. Also, the presence of EDTA lowers the observed melting
      temperature in thermal ramp experiments and the midpoint denaturant concentration
      in equilibrium chemical unfolding experiments, further suggesting that the
      clusters also play a structural role in the maintenance of the conformation of
      the folded state.

PMID- 15578279
TI  - [Night vision disturbances: should measurement methods and criteria be
      standardized?].

PMID- 15578280
TI  - [Microincisional phacoaspiration: will it be congenital cataract's future?].

PMID- 15578281
TI  - [Phacoemulsification cataract surgery in vitrectomized eyes].
AB  - OBJECTIVE: This study focuses on determining the intra- and post-operative
      complications stemming from technical difficulties, anatomical aspects,
      intraoperatory management and visual outcome of post-vitrectomized patients that
      undergo phacoemulsification. METHOD: In this prospective, longitudinal,
      observational and descriptive study phacoemulsification was performed in 25 post
      vitrectomized eyes that required cataract surgery. Pre-surgical variables: sex,
      age, affected eye, visual accuity, underlying vitreoretinal disease, anterior
      segment morphological findings such as: cataract density and pupil alterations.
      Intrasurgical variables: characteristic of anterior chamber and pupil,
      phacoemulsification technique and time and the presence of complications. Post
      surgical variables were also registered: visual capacity and the presence of
      complications. Minimum six-month follow-up period. RESULTS: The average interval
      between pars plana vitrectomy and phacoemulsification was 18.5 months. Silicone
      oil was the most frequent tamponade used in our serie (44%). Biomicroscopical
      findings were miosis 28% and posterior synechies 24%. The average interval of
      phaco time was 2.26 minutes. The intraoperative findings were fluctuations in the
      anterior chamber depth (24%) and anterior capsular tears (12%). The postoperative
      complications most frequently seen were posterior capsular plaque (28%) and
      corneal edema (16%). CONCLUSIONS: Phacoemulsification is a safe and effective
      technique in eyes after pars plana vitrectomy that require cataract surgery. The
      surgeon must be aware of the morphological and anatomical findings of these eyes.
      Visual rehabilitation will generally be determined by the presence of an
      underlying vitreo-retinal pathology.

PMID- 15578282
TI  - [Treatment of persistent epithelial defects using autologous serum application].
AB  - PURPOSE: To study the impact of topical treatment with autologous serum on the
      clinical evolution of persistent corneal epithelial defects (PED) and to observe
      its effect on squamous metaplasia in 7 cases of dry eye. PATIENTS AND METHODS: In
      this prospective, clinical, non-comparative case series study we evaluated a
      total of 17 eyes (14 patients). We analized the clinical evolution (fluorescein
      staining, Schirmer's I and II tests and photographic control) of PED in these
      patients, to whom 20% autologous serum eyedrops were applied for 28 days. Using
      impression cytology technique (Tseng's method) we evaluated the involution of
      squamous metaplasia in 7 eyes of 4 patients with ocular cicatricial pemphigoid
      and dry eye who were treated with autologous serum. The Wilconxon test was used
      for the statistical treatment of the data. RESULTS: The epithelial defect healed
      within 2 weeks in 6 eyes (35.2%). Eight eyes (47%) healed within 2-4 weeks and 3
      eyes (17.6%) did not heal after week 4. The duration of PED, before serum therapy
      was 36 days. Six of seven eyes treated with autologous serum presented an
      involution of squamous metaplasia 28 days after initiation of the serum drops.
      CONCLUSIONS: Autologous serum treatment accelerates PED healing. Autologous serum
      application causes an involution of squamous metaplasia.

PMID- 15578283
TI  - [Clinical-pathologic characteristics of uveal melanoma in Mexican patients under
      thirty years old].
AB  - PURPOSE: To analyze the clinicopathologic characteristics of uveal melanoma in
      Mexican patients under thirty years old. METHODS: We reviewed the cases from the
      Service of Ophthalmic Pathology with histopathologic diagnosis of uveal melanoma
      from 1957 to March 2002. The data analyzed were: age, gender, affected eye,
      clinical diagnosis, size, cellular type, mitotic index, lymphocytic infiltrate,
      vascular pattern, necrosis, vascular and/or intraocular invasion and orbital
      extension. RESULTS: We reviewed 122 cases diagnosed with uveal melanoma, and 14
      patients were younger than 30 years old (11.4%). The mean age was 21.7 years,
      with female preponderance. Preoperative clinical diagnoses were uveal melanoma in
      92.8%, most of the cases originated from choroid. The most frequent cellular type
      was spindle cells and 3 and 4 Folberg's vascular patterns. CONCLUSIONS: Our
      results suggest that the clinicians should consider uveal melanoma more
      frequently as another differential diagnosis in patients under thirty years with
      an intraocular tumor. The histological characteristics found have been correlated
      with a better prognosis.

PMID- 15578284
TI  - [Tuberculous meningitis. One case: ophthalmic complications].
AB  - CASE REPORT: An 18 year old female suffering from tuberculous meningitis with
      bilateral amaurosis, ophthalmoplegia, other cranial nerve palsies and loss of
      consciousness, is presented. DISCUSSION: Tuberculous meningitis is a rare cause
      of basal arachnoiditis with a bad prognosis. Possible causes of visual acuity
      loss and ophthalmoplegia are discussed and a favourable outcome without sequelae
      is noteworthy in our case.

PMID- 15578285
TI  - [Sympathetic ophthalmia post-vitrectomy following trauma and perfluorocarbon
      liquid tamponade].
AB  - CASE REPORT: We report a case of sympathetic ophthalmia (SO) developed after
      blunt trauma and vitrectomy (complicated with a massive suprachoroidal
      hemorrhage) using perfluorocarbon liquid (PFCL) for tamponade. DISCUSSION: The
      presentation of SO in a vitrectomized patient after severe blunt trauma with
      extended intra-ocular tamponade with PFCL could support the hypothesis that
      chronic inflammation caused by PFCL could have contributed to the development of
      SO. Nevertheless, there are other possible causal factors such as the trauma, the
      vitrectomy itself or the choroidal detachment with possible uveal incarceration
      at wound sites.

PMID- 15578286
TI  - [A new device for vitreous biopsy].
AB  - PURPOSE/METHODS: Description of a simply-made device for obtaining vitreous
      biopsies. RESULTS/CONCLUSIONS: This new device allows the surgeon to control
      aspiration, thereby enabling the obtention of many vitreous biopsies both diluted
      and undiluted.

PMID- 15578287
TI  - [Progression of thyroid orbit disease after retrobulbar anesthesia].
AB  - CASE REPORT: We present a 71 year-old woman with good control of her eye disease
      who developed a severe Graves' ophthalmopathy after retrobulbar anesthesia for
      cataract surgery. DISCUSSION: Local pressure in the retrobulbar compartment can
      cause the development of a severe ophthalmopathy in a patient with Graves'
      ophthalmopathy.

PMID- 15578288
TI  - [Efficiency of voriconazole in fungal keratitis caused by candida albicans].
AB  - CASE REPORT: A 70-year-old woman, with a history of diabetes and persistent
      corneal ulceration, developed a severe keratitis caused by Candida albicans. It
      evolved rapidly to corneal perforation in spite of treatment with topical
      amphotericin B and oral itraconazole. An amniotic membrane transplant was
      performed as an emergency, associated with systemic administration of
      voriconazole. The infection was solved successfully, although the patient needed
      a penetrating keratoplasty to restore the corneal transparency. DISCUSSION:
      Fungal keratitis caused by Candida albicans usually follows an aggressive course
      and may simulate a bacterial aetiology. Voriconazole is a new antifungal drug
      that appears to be very effective in the management of ocular infections caused
      by many filamentous and levaduriform fungi.

PMID- 15578289
TI  - [Stevens-Johnson's syndrome after treatment for ocular toxoplasmosis].
AB  - CLINICAL CASE: We present a case of a 9 year-old male, who was treated with
      sulfadiacine, pirimetamine and folinic acid following diagnosis of an active
      toxoplasmic chorioretinitis. After 9 days of treatment he developed serious
      multiorganic mucocutaneous lesions and was diagnosed with Stevens-Johnson's
      syndrome. DISCUSSION: Stevens-Johnson's syndrome is a potentially fatal
      multiorganic disease, where drugs are clearly linked as causal factors. Fifty per
      cent of cases progress to severe ocular disease. The multiorganic aspect of the
      disease and its severity demand an early diagnosis and a multidisciplinary
      treatment.

PMID- 15578290
TI  - [Vision allegories].

PMID- 15578291
TI  - [The terrible prediction of the painter Victor Brauner (1903-1966)].

PMID- 15578292
TI  - Selective endoscopic cholangiography for the detection of common bile duct stones
      in patients with cholelithiasis.
AB  - BACKGROUND AND STUDY AIMS: The detection and management of common bile duct (CBD)
      stones in patients undergoing laparoscopic cholecystectomy continues to be
      controversial. Several diagnostic and therapeutic strategies have been suggested.
      These include intraoperative cholangiography, selective endoscopic retrograde
      cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography, and
      endoscopic ultrasonography. The aim of this study was to evaluate the efficacy of
      selective ERCP in detecting CBD stones in patients with cholelithiasis before
      laparoscopic cholecystectomy. PATIENTS AND METHODS: In a prospective study,
      patients with cholelithiasis who presented during a 6-year period were assessed
      on a selective basis with ERCP for suspected CBD stones before laparoscopic
      cholecystectomy. ERCP was carried out if the patient had any of the following
      criteria: a dilated CBD on ultrasound, gallstone pancreatitis, or abnormal liver
      function tests. Intraoperative cholangiography was not performed in any of the
      patients. Long-term follow-up was undertaken. RESULTS: The study included 427
      patients. On the basis of selective criteria, ERCP was carried out in 41 patients
      (9.6 %), with confirmed CBD stones in 22 cases (53.7 %). The most useful
      predictor of CBD stones on ERCP was the presence of a dilated CBD in association
      with abnormal liver function tests. In this situation, CBD stones were identified
      in 14 of 17 cases (82 %). Abnormal liver function tests alone had a sensitivity
      of 50 % (four of eight). All other parameters used in isolation had a lower
      detection rate. During a median follow-up period of 6 years (range 1-10 years),
      six of 386 patients (1.6 %) with initially normal imaging and biochemical tests
      presented again with retained stones. All were successfully managed by ERCP and
      sphincterotomy. There were no major complications. CONCLUSIONS: Preoperative
      selective ERCP is effective in detecting clinically significant CBD stones.
      However, there is a high false-negative rate when a single criterion is used to
      guide therapy. Multivariate analysis of preoperative parameters for risk
      stratification, in conjunction with other imaging modalities, may make it
      possible to minimize unnecessary ERCPs.

PMID- 15578293
TI  - Association of periampullary duodenal diverticula with bile duct stones and with
      technical success of endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND AND STUDY AIMS: Periampullary diverticula are thought to be associated
      with bile duct stones. However, studies to date have been inconclusive as they
      have not taken into account the influence of age. Our study analysed the
      association of diverticula with bile duct stones and with the technical success
      of endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: A
      total of 415 consecutive patients who were undergoing ERCP were prospectively
      entered into a database. Of these patients, 83 (20 %; mean age 73 years; 34 men,
      49 women) were found to have diverticula. The age-matched control group comprised
      261 patients (mean age 72 years; 106 men, 155 women). The chi-squared test was
      used to analyse the results. RESULTS: In the diverticula group, 53 (64 %) had
      bile duct stones, compared with 86 (33 %) of the controls ( P < 0.0001), with an
      odds ratio of 3.6. Significantly more patients in the diverticula group had
      primary bile duct stones; also significantly more of them had stones in both the
      bile duct and gallbladder. There was no difference between the two groups with
      regard to previous history of pancreatitis (10 % in the diverticula group vs. 11
      % in the control group). There were no significant differences found between the
      diverticula group and the control group in terms of successful duct cannulation
      (94 % in both groups), sphincterotomies (96 % vs. 98 %) or stone extraction (94 %
      vs. 88 %). The incidence of complications was similar in the two groups
      (diverticula group 5 % vs. control group 3.3 %). CONCLUSIONS: Periampullary
      diverticula are associated with an increased incidence of bile duct stones but
      not with pancreatitis. Diverticula did not cause any technical difficulties at
      ERCP or increase the risk of complications.

PMID- 15578294
TI  - Comparison of capsule endoscopy and magnetic resonance imaging for the detection
      of polyps of the small intestine in patients with familial adenomatous polyposis
      or with Peutz-Jeghers' syndrome.
AB  - BACKGROUND AND STUDY AIMS: We have conducted a study to compare the diagnostic
      yields of magnetic resonance imaging (MRI) and capsule endoscopy for the
      detection of small-bowel polyps in patients with inherited polyposis syndromes.
      PATIENTS AND METHODS: MRI was performed in 20 patients, with either Peutz
      Jeghers' syndrome (PJS; n = 4) or familial adenomatous polyposis (FAP; n = 16),
      and capsule endoscopy was done the next day. The number, size, and location of
      polyps were analyzed. RESULTS: Overall, 448 polyps ranging from about 1 mm to 30
      mm in size were detected in eight patients by capsule endoscopy, whereas with MRI
      only 24 polyps all bigger than 5 mm could be seen in the four PJS patients.
      CONCLUSIONS: Polyps bigger than 15 mm were detected similarly with capsule
      endoscopy and MRI, whereas smaller polyps were seen much more often with capsule
      endoscopy. Polyps smaller than 5 mm were exclusively seen with capsule endoscopy.
      However, location of the detected polyps and determination of their exact sizes
      was more accurate by MRI.

PMID- 15578295
TI  - Wireless capsule endoscopy for evaluation of phenotypic expression of small-bowel
      polyps in patients with Peutz-Jeghers syndrome and in symptomatic first-degree
      relatives.
AB  - BACKGROUND AND STUDY AIMS: Peutz-Jeghers syndrome (PJS) is an inherited
      gastrointestinal hamartomatous polyposis disorder. Small-bowel intussusception
      and bleeding are the most common complications, and malignancy may also occur.
      Survey of the gastrointestinal tract, particularly of the small bowel, is
      difficult and current recommendations for management syndrome are ambiguous. We
      evaluated the feasibility of capsule endoscopy for identifying phenotypic
      expression of small-bowel polyps in patients with full-blown PJS and a previous
      diagnosis of gastrointestinal polyposis, and in symptomatic kindred of PJS
      patients with no previous diagnosis of gastrointestinal polyposis. PATIENTS AND
      METHODS: Two groups were studied: group A consisted of 14 patients with
      gastrointestinal polyposis, eight of whom had undergone previous small-intestine
      surgery; group B consisted of six symptomatic first-degree relatives of PJS
      patients; these patients had previous negative gastrointestinal endoscopic
      examinations. RESULTS: Numerous polyps were detected in all patients in group A.
      Most polyps were sessile, but the larger polyps tended to be pedunculated. Polyp
      density was highest in the jejunum (greater than in the ileum and duodenum).
      Seven patients had at least one large polyp (> 11 mm) and five of these patients
      subsequently underwent enteroscopy, which revealed that capsule endoscopy had
      correctly identified all the patients with large polyps, but had missed 20 % of
      the total number of large polyps in these patients. No polyps were detected by
      capsule endoscopy in group B patients, despite the excellent visualization of the
      small intestine. In all patients, the capsules were expelled within 24 hours,
      without complications, and the procedure was well tolerated. CONCLUSIONS: Capsule
      endoscopy is an effective and well-tolerated method for evaluating small-bowel
      pathology in patients with PJS.

PMID- 15578296
TI  - Clinical usefulness of the endoscopic video capsule as the initial intestinal
      investigation in patients with obscure digestive bleeding: validation of a
      diagnostic strategy based on the patient outcome after 12 months.
AB  - BACKGROUND AND STUDY AIMS: In patients with obscure digestive bleeding, the
      bleeding source is frequently located in the small bowel. Capsule endoscopy (CE)
      is an effective method of investigating the whole small bowel in such patients.
      In the present study, a diagnostic approach was tested in patients with obscure
      digestive bleeding in which CE was included as the initial examination of the
      small bowel when the esophagogastroduodenoscopy (EGD) and colonoscopy findings
      were normal. PATIENTS AND METHODS: Patients admitted between October 2000 and
      February 2002 for obscure digestive bleeding underwent CE as the initial
      intestinal investigation, and the further management was decided on the basis of
      the results. After 12 months, follow-up data were obtained from all patients and
      referring physicians. The positive predictive value was calculated as the
      percentage of patients in whom CE detected a relevant lesion, and the negative
      predictive value as the percentage of patients with normal CE in whom no
      intestinal lesion was detected during the follow-up period. RESULTS: Forty-four
      patients (21 men, 23 women, aged 63 +/- 17 y) were included in the study. Twenty
      two had overt bleeding and 22 had occult bleeding. CE detected an intestinal
      lesion in 18 patients (41.9 %)-- nine with angiomas, five with ulcers, one with a
      tumor, two with portal hypertension, and one with ischemic ileitis. The findings
      were normal in 17 patients (39.5 %). CE detected upper gastrointestinal lesions
      missed at EGD in four patients and blood in the stomach in two patients or in the
      proximal colon in three, leading to new endoscopies. Intestinal lesions detected
      at CE were treated as follows: push enteroscopy with treatment in eight patients,
      surgery in four, and medical treatment in six. In eight patients who underwent
      push enteroscopy, the procedure did not reveal lesions missed by CE. After 1
      year, 15 of the 18 patients treated for intestinal lesions had no further
      bleeding and no anemia; one died after surgery (for resection of an ischemic
      intestinal loop), one relapsed, and one was diagnosed with a different intestinal
      condition. In all patients with extraintestinal lesions or blood detected at CE,
      further endoscopies led to diagnosis and therapy, with a favorable outcome. In
      patients with normal CE, no intestinal lesion was detected, but an
      extraintestinal source of bleeding was diagnosed and treated in nine patients (in
      the upper gastrointestinal tract in five cases and in the colon in four). Three
      patients had anemia of hematological origin and four had inadequate iron intake.
      The positive predictive value of CE was 94.4 % in patients with intestinal
      lesions, and the negative predictive value was 100 % in patients with normal CE
      findings. CONCLUSIONS: In patients with obscure digestive bleeding, CE positively
      predicted the intestinal diagnosis or normal status in 95.5 % of cases. A
      diagnostic approach to obscure digestive bleeding that includes CE after the
      initial endoscopic work-up thus appears to be a valid strategy for small-bowel
      examinations.

PMID- 15578297
TI  - Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a
      capsule-endoscopic study.
AB  - BACKGROUND AND STUDY AIMS: Hereditary hemorrhagic telangiectasia (HHT) is an
      autosomal-dominant vascular disorder leading to telangiectases and arteriovenous
      malformations of the skin, mucosa, and viscera. Telangiectases in the upper
      gastrointestinal tract are known, but data regarding possible small-bowel
      involvement are scarce due to the technical difficulty of exploring the entire
      gastrointestinal tract. The aim of the present study was to use capsule endoscopy
      (CE) to determine the prevalence of small-bowel telangiectases in HHT patients.
      PATIENTS AND METHODS: From December 2001 to September 2002, 20 consecutive adult
      HHT patients at an interdepartmental HHT center were prospectively evaluated. All
      patients underwent esophagogastroduodenoscopy (EGD) followed by CE within 24 h.
      The telangiectases were scored according to commonly accepted criteria by two
      endoscopists and two observers of the video-capsule images, who were blinded to
      each other's findings. RESULTS: EGD revealed gastric telangiectases in 15 of the
      20 patients (75 %), while CE demonstrated small-bowel involvement in 10 of 18
      patients (56 %; images were not recorded for two patients due to battery
      failure). No preferential site for telangiectasia was found between the jejunum
      and the terminal ileum. All patients who were positive on CE were also found to
      have gastric involvement at EGD. Patients with small-bowel telangiectases were
      significantly older than those without (62.5 years vs. 45 years; P < 0.02).
      CONCLUSIONS: This study established a 56 % prevalence of small-bowel
      telangiectases in patients with HHT. This new endoscopic technique will probably
      change the etiological diagnosis of occult bleeding in HHT patients (which is too
      often attributed only to epistaxis) and may also be able to alter treatment
      strategies in HHT patients with gastrointestinal bleeding.

PMID- 15578298
TI  - Magnifying endoscopy combined with narrow band imaging system for early gastric
      cancer: correlation of vascular pattern with histopathology (including video).
AB  - BACKGROUND AND STUDY AIMS: The narrow band imaging (NBI) system consists of a
      sequential electronic endoscope system and a source of light equipped with new
      narrow band filters, yielding very clear images of microvessels on mucosal
      surfaces. The aim of this prospective study was to measure the correlation
      between the magnified images obtained with the NBI system and the histological
      findings, especially with regard to the vascular pattern. In addition, three
      dimensional images of microvessels were reconstructed using a laser scanning
      microscope. PATIENTS AND METHODS: Between July 2001 and August 2003, 165 patients
      with depressed-type early gastric cancer lesions were enrolled in the study. The
      lesions were carefully observed with magnification using the NBI system. The
      images, the pathological characteristics of the lesions, and three-dimensionally
      reconstructed images of the microvascular networks in biopsied specimens were
      carefully analyzed. The microvascular patterns were classified into three groups:
      A, fine network; B, corkscrew; and C, unclassified pattern. The endoscopic images
      were compared with the histological findings. RESULTS: Of the three types of
      filter available for use with the NBI system, microvascular formation was best
      enhanced in B mode images produced using short wavelengths, which focus on the
      superficial mucosal layer. Among 109 cases of differentiated adenocarcinoma, the
      group A microvascular pattern was observed in 72 cases (66.1 %). Among 56 cases
      of undifferentiated adenocarcinoma, the group B pattern was observed in 48 cases
      (85.7 %; P = 0.0011) The microvascular structure observed using the NBI system
      corresponded with the superficial mucosal layer in the three-dimensional images
      obtained using laser scanning microscopy and the resected specimens. CONCLUSIONS:
      Magnifying endoscopy performed in combination with the NBI system is not
      sufficient to replace conventional histology, but is capable of predicting the
      histological characteristics of gastric cancer lesions.

PMID- 15578299
TI  - Efficacy of argon plasma coagulation in nonvariceal upper gastrointestinal
      bleeding.
AB  - BACKGROUND AND STUDY AIMS: Various methods of endoscopic hemostasis have been
      described. However, few reports have investigated the efficacy of argon plasma
      coagulation (APC) in the treatment of upper gastrointestinal bleeding. The aim of
      this study was to evaluate the efficacy of APC in various types of upper
      gastrointestinal bleeding. PATIENTS AND METHODS: The present study was designed
      as a prospective and observational study. A total of 254 consecutive patients
      with upper gastrointestinal bleeding (excluding variceal bleeding) were primarily
      treated using APC. If it was difficult to achieve complete hemostasis with APC
      alone, injection of a hypertonic saline-epinephrine solution and clipping were
      carried out. The initial hemostasis rate, rate of recurrent bleeding after APC,
      permanent hemostasis rate, and mean procedure time were evaluated. RESULTS:
      Initial hemostasis with APC alone was achieved in 193 of the 254 patients (75.9
      %). With the assistance of other methods as well, initial hemostasis was achieved
      in 253 patients (99.6 %). Among the 193 patients treated with APC alone,
      recurrent bleeding was observed in 11 cases (11 of 193, 5.7 %). With one
      exception, these cases of recurrent bleeding were controlled with APC alone
      again; permanent hemostasis was thus ultimately achieved with APC alone in 192 of
      the 254 patients (75.5 %). The mean procedure time was 8 min. No complications
      (such as perforation) were observed with the APC treatment. CONCLUSIONS: These
      data indicate that APC is a safe, quick, and effective method of treating various
      types of nonvariceal upper gastrointestinal bleeding and that it can be a
      powerful tool for endoscopic hemostasis.

PMID- 15578300
TI  - Chromoendoscopy using indigo carmine dye spraying with magnifying observation is
      the most reliable method for differential diagnosis between non-neoplastic and
      neoplastic colorectal lesions: a prospective study.
AB  - BACKGROUND AND AIMS: Differential diagnosis between non-neoplastic and neoplastic
      lesions is very important at colonoscopy, since removal or biopsy of non
      neoplastic polyps wastes time and resources. We therefore conducted a prospective
      study to examine whether indigo carmine dye spraying with and without
      magnification is more reliable than the conventional method for differential
      diagnosis. PATIENTS AND METHODS: 122 patients with 206 lesions of 10 mm or
      smaller were recruited into this study. All lesions detected on colonoscopy were
      first diagnosed using the conventional view, then at chromoendoscopy using 0.2 %
      indigo carmine, and finally at chromoendoscopy with magnification. The diagnosis
      at each step were recorded consecutively. All lesions were finally categorized as
      neoplastic or non-neoplastic according to pit pattern; non-neoplastic lesions
      were biopsied for histological evaluation, and all the neoplastic ones were
      removed endoscopically. The accuracy rate of each type of endoscopic diagnosis
      was evaluated, using histological findings as reference. RESULTS: Histologically,
      46 lesions (22 %) were non-neoplastic and 160 (78 %) were neoplastic. The overall
      diagnostic accuracies by conventional view, chromoendoscopy, and chromoendoscopy
      with magnification were 84.0 % (173/206), 89.3 % (184/206) and 95.6 % (197/206),
      respectively. CONCLUSION: Chromoendoscopy with magnification is the most reliable
      method for determining whether a colorectal lesion is non-neoplastic or
      neoplastic.

PMID- 15578301
TI  - Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot
      study.
AB  - BACKGROUND AND STUDY AIMS: A newly developed narrow-band imaging (NBI) technique,
      in which modified optical filters were used in the light source of a video
      endoscope system, was applied during colonoscopy in a clinical setting. This
      pilot study evaluated the clinical feasibility of the NBI system for evaluating
      colorectal lesions. PATIENTS AND METHODS: A total of 43 colorectal lesions in 34
      patients were included in the study. The quality of visualization of colorectal
      lesions and the accuracy of differentiation between neoplastic and non-neoplastic
      lesions using the NBI system were evaluated in comparison with results from
      conventional colonoscopy and with chromoendoscopy. RESULTS: For pit pattern
      delineation, NBI was superior to conventional endoscopy (P < 0.001), but inferior
      to chromoendoscopy (P < 0.05). NBI achieved better visualization of the mucosal
      vascular network and of the hue of lesions than conventional endoscopy (P <
      0.05). However there was no significant difference between NBI and
      chromoendoscopy in differentiating neoplastic from non-neoplastic lesions (both
      techniques had a sensitivity of 100 % and a specificity 75 %). This was better
      than the results of conventional colonoscopy (sensitivity 83 %, specificity 44 %;
      P < 0.05 for specificity). CONCLUSIONS: These results suggest that in the
      examination of colonic lesions the NBI system provides imaging features
      additional to those of both conventional endoscopy and chromoendoscopy. For
      distinguishing neoplasms from non-neoplastic lesions, NBI was equivalent to
      chromoendoscopy.

PMID- 15578303
TI  - ERCP: targeting the stone.

PMID- 15578302
TI  - Tuberculous colonic strictures: impact of dilation on diagnosis.
AB  - BACKGROUND AND STUDY AIM: Colonic strictures are commonly encountered in patients
      with colonic tuberculosis. If the colonoscope cannot be negotiated past the
      stricture the procedure is abandoned, the colonic mucosa proximal to the
      stricture cannot be inspected, and therefore lesions in these locations may be
      missed. PATIENTS AND METHODS: 130 patients with colonic tuberculosis were
      studied. Of these 22 (17 %) had impassable colonic strictures. These strictures
      were dilated, the colonic mucosa proximal to the strictures was then inspected,
      and biopsies were obtained from lesions of suspicious appearance. RESULTS: All
      strictures could be dilated. No abnormality was found in 11 patients. In the
      other 11 patients one or more additional findings were noted on colonoscopy after
      dilation. A second stricture was found in three patients. Nodularity and/or
      ulceration was observed in the colon proximal to the site of the primary
      stricture in ten patients. Dilation of the strictures and histological
      examination of the biopsy from target lesions of the proximal colon contributed
      to making the definitive diagnosis in five patients. The diagnosis was not
      altered in the remaining six patients. CONCLUSION: Dilation of colonic strictures
      facilitates inspection of the colonic mucosa proximal to the strictures, enabling
      biopsy of target lesions. This approach offers important diagnostic clues and
      confirmation of the diagnosis in several patients in whom lesions might be missed
      if strictures are not dilated.

PMID- 15578304
TI  - Capsule status 2004: what is the outcome in bleeding? Are there really additional
      indications?

PMID- 15578305
TI  - Endoscopic appearance of dysplasia in ulcerative colitis and the role of
      staining.

PMID- 15578306
TI  - Bile leakage and resultant bile peritonitis during or after diagnostic
      laparoscopy: an unpredictable event.
AB  - Bile peritonitis secondary to bile leakage is a rare complication of laparoscopy
      guided liver biopsy. We report two cases of bile peritonitis occurring,
      respectively, during and 6 days after liver biopsy in patients with an initial
      diagnosis of intrahepatic cholestasis associated with chronic pancreatitis. In
      both cases, bile leakage was first managed by compression with a palpating probe
      and, at onset or worsening of symptoms, by suture during laparotomy. However,
      while the first patient progressed uneventfully during the postoperative period,
      the second died 13 days after laparotomy. In the latter patient, bile leakage was
      associated with bleeding from the biopsy site with consequently diminished
      peritoneal irritation and delayed onset of symptoms. In this patient, pancreatic
      carcinoma, of which evidence was found at autopsy, may also have contributed to
      the fatal outcome. In conclusion, bile leakage and secondary peritonitis may also
      occur in the absence of dilation of the biliary tree and may be fatal, especially
      if not recognized and treated early.

PMID- 15578307
TI  - Intramural bronchogenic cysts mimicking solid tumors.

PMID- 15578308
TI  - Antibiotic prophylaxis for digestive endoscopy.

PMID- 15578310
TI  - Failure to diagnose colorectal carcinoma at colonoscopy.

PMID- 15578311
TI  - EMR.

PMID- 15578312
TI  - Traumatic disruption of the proximal hepatic duct: endoscopic treatment after
      failure of surgical repair.

PMID- 15578313
TI  - Endoscopy-assisted ferromagnetic foreign-body removal with a novel magnetic
      instrument.

PMID- 15578314
TI  - Depressed-type hyperplastic lesion in the colon.

PMID- 15578315
TI  - A new use for the rotatable sphincterotome as an aid for stenting malignant
      gastrointestinal tract stenoses.

PMID- 15578316
TI  - Acute esophageal necrosis (black esophagus): endoscopic and histopathologic
      appearance.

PMID- 15578317
TI  - Gastric intramucosal carcinoma in a small hyperplastic foveolar polyp.

PMID- 15578318
TI  - [Epidemiological investigations of the chances of preventing, recognizing early
      and optimally treating chronic diseases in an elderly population (ESTHER study)].
AB  - BACKGROUND AND OBJECTIVE: Demographic changes in Germany will result in a marked
      rise in the prevalence of chronic diseases, presenting a central challenge in the
      coming decades. The ESTHER study on this question has as its objective to bring
      about innovative ways for the early recognition and prevention of diseases in the
      elderly. We herein give the concept of the study and the results of the basic
      enquiry. PATIENTS AND METHODS: The ESTHER study includes 9961 persons, aged
      between 50 and 74 years, who had a health check-up by their general practitioner.
      Standardized questionnaires for doctors and patients were used in addition to the
      check-up test to provide extensive basic data on risk factors, previous
      illnesses, family history and relevant items on life style. Blood, urine and
      stool samples were kept for later testing RESULTS: This cohort had a high
      prevalence of known risk factors for various chronic diseases, especially of the
      cardiovascular system. 42% of the cohort already had a history of hypertension,
      40% of hyperlipidaemia, 11% had diabetes mellitus and 9% coronary heart disease.
      There was an association with obesity (present in many). The check-up test newly
      diagnosed one of the diseases or the presence of relevant risk factors in 13.4%.
      CONCLUSION: The high prevalence of risk factors for chronic diseases in the
      elderly underlines the urgency of stressing preventive measures. The ESTHER study
      - because of its long-term follow-up and saved specimens for later testing -
      provides an excellent basis for identifying new risk factors and risk indicators
      of chronic diseases.

PMID- 15578319
TI  - [Rest angina caused by coronary spasm].
AB  - HISTORY AND PHYSICAL EXAMINATION: A 70-year-old woman with recurrent angina at
      rest and dyspnea was admitted for coronary angiography. Prior to the admission an
      ECG showed new negative T-waves in the precordial leads, which have completely
      disappeared the day after. Clinical examination revealed a low systolic murmur
      over the aortic valve and a low murmur over the left groin artery. The other
      examination findings were normal. INVESTIGATIONS: Exercise ECG revealed no signs
      of ischemia. In the coronary angiography a plaque in the left circumflex artery
      without significant lumen reduction could be detected. Intracoronary
      administration of acetylcholine induced a spasm in the left circumflex artery
      with total lumen occlusion with reproduction of intense chest pain. After
      injection of nitroglycerin coronary spasm and chest pain were reversible
      TREATMENT AND CLINICAL COURSE: After the diagnosis of vasospastic angina pectoris
      medical treatment with isosorbide dinitrate and amlodipine was initiated.
      Additionally ACE- and CSE-inhibitors were prescribed to improve endothelial
      dysfunction. After one year the patient was free of symptoms. CONCLUSION:
      Coronary spasm can cause angina at rest. After confirmation of diagnosis an
      appropriate medical therapy could be applied and other unnecessary examinations
      including further coronary angiographies could be prevented.

PMID- 15578320
TI  - [Cardiovascular risks of selective COX-2-inhibitors].

PMID- 15578321
TI  - [Coronary spasm in normal coronary arteries].

PMID- 15578322
TI  - [The competence network "acute and chronic leukemias"].
AB  - Leukemias are a challenge and a cost factor to society because of their frequency
      in all age groups. They also serve as a model for a variety of diseases and
      possess exemplary relevance for basic research and patient care. Leukemia
      research and therapy have achieved high standards and even a leading position in
      Germany with regard to clinical trials, standardization of diagnostics and
      molecular studies of prognostic factors, signal transduction and gene expression.
      Progress is hampered, however, by fragmentation of leukemia trial groups,
      diagnostic approaches and treatment research activities. A network was therefore
      created to integrate the leading leukemia trial groups on chronic myeloid
      leukemia (CML), acute myeloid leukemia (AML), acute lymphatic leukemia (ALL),
      myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (CMPD)
      and their interdisciplinary partners (diagnostics, treatment research, biometry)
      in cooperation with basic research and pharmaceutical industry to foster
      advancements in leukemia-related research and health care through clinical
      trials, promotion of translational research, introduction of standards for
      diagnostics and therapy, and development of evidence-based guidelines.
      Achievements include establishment of central information, communication and
      management structures, creation of an AML intergroup comprising five study
      groups, formation of a myelodysplastic syndromes study group and establishment of
      platforms for diagnostics, genomics and proteomics, and medical informatics.
      Exchange of scientific progress is mediated by intra- and internet, bi-annual
      newsletters, regular project group meetings and annual network symposia. Already
      now, the network structures leukemia therapy and research in Germany and supports
      the spread of scientific excellence in the field of leukemias.

PMID- 15578323
TI  - [Meningococcal disease].
AB  - Due to a high complication and case fatality rate, meningococcal diseases are
      important health problems both in tropical countries experiencing severe
      epidemics as well as in countries of moderate climate zones. Worldwide N.
      meningitidis of sero-groups A, B, and C are predominant and to a lesser extent
      serogroups W (135) and Y play a role, whereas in Europe more than 90 % of
      meningococcal diseases are caused by serogroups B and C of N. meningitidis. In
      Germany and other developed countries the majority of cases occur in very young
      children and adolescents. Since many years, meningococcal polysaccharide vaccines
      against diseases due to N.meningitidis serogroup A, C, Y and W (135) are
      commercially available. Unfortunately, a vaccine against diseases caused by N.
      meningitidis serogroup B is still under development. The recently developed and
      licensed conjugated meningococcal vaccines against N. meningitidis serogroup C
      are also protective against disease in very young children. Eight countries in
      Western Europe as well as Australia have already established country-wide
      immunization programs for children and adolescents. Within only 2 to 3 years,
      well managed programs have achieved far-reaching control of meningococcal C
      disease in UK and the Netherlands. In Germany, the Advisory Committee on
      Immunization (STIKO recommends immunization for selected risk groups. The current
      increase of the percentage of meningococcal C diseases to 28 - 30 % gives reason
      for further discussion regarding immunization strategies. How-ever, the STIKO
      expressively declares, that in addition to the recommendation for risk groups,
      the physician can use all vaccines licensed in Germany without any restriction.
      It is his/her responsibility to advice the patients regarding immunization
      possibilities against the life-threatening meningococcal disease, particularly if
      cases are occurring.

PMID- 15578324
TI  - [Individualization of diagnosis and therapy].

PMID- 15578325
TI  - [Absence from ward treatment].

PMID- 15578328
TI  - The impaired response of non-obese hereditary hypertriglyceridemic rats to
      glucose load is associated with low glucose storage in energy reserves.
AB  - The aim of the study was to determine the contribution of skeletal muscle,
      adipose tissue and liver to the impaired glucose clearance manifesting itself
      during the initial phase of OGTT in a non-obese animal model of insulin
      resistance, hereditary hypertriglyceridemic (HHTg) rats. Glucose utilisation and
      storage in insulin target tissues in vivo and in vitro after a glucose load (3
      g/kg b. wt.) administered intragastrically following overnight fasting was
      compared in adult male HHTg rats and Wistar normotriglyceridemic controls after
      short-term (2 wk) high-sucrose (70 % calories as sucrose) feeding period. In
      comparison with normotriglyceridemic controls, in HHTg rats the glucose
      administration did not stimulate GLUT4 translocation to the plasma membrane in
      skeletal muscle and adipose tissue that was associated with decreased glucose
      utilisation by these tissues in vitro. The acute glucose supply did not result in
      increased glycogen synthesis in the liver and fatty acid synthesis de novo in
      adipose tissue. On the contrary, the serum glucose, triglyceride and free fatty
      acid levels remained elevated. In conclusion, in the tissues of HHTg rats,
      despite the increased insulinemia, the processes leading toward increased glucose
      utilisation and processes transforming glucose into storage forms, such as
      triglycerides in adipose tissue and glycogen in skeletal muscle and liver, did
      not start within this time interval. The combination of the impaired glucose
      utilisation and the impaired glucose storage in energy reserves leads to higher
      glycaemia following glucose load in HHTg rats.

PMID- 15578329
TI  - Introductory experience with the continuous glucose monitoring system (CGMS;
      Medtronic Minimed) in detecting hyperglycemia by comparing the self-monitoring of
      blood glucose (SMBG) in non-pregnant women and in pregnant women with impaired
      glucose tolerance and gestational diabetes.
AB  - OBJECTIVE: To assess the detection rate of hyperglycemia with a continuous
      glucose monitoring system compared to a self-monitoring blood glucose profile in
      non-pregnant, non-diabetic pregnant women, and patients with impaired glucose
      tolerance or gestational diabetes.. METHODS: Eight non-pregnant (NP) and 56
      pregnant women (17 dietary-treated gestational diabetics (GDM), 15 women with
      impaired glucose tolerance (IGT), and 24 non-diabetic pregnant women (NDP))
      underwent a 72-hour measurement with the CGMS (Medtronic Minimed, Northridge, CA,
      USA). Self-monitored blood glucose measurements, performed 30 minutes before and
      120 minutes after each meal, were compared to the duration of hyperglycemia
      monitored by the continuous glucose monitoring system. RESULTS: No clinically
      observable infection was found at the subcutaneous tissue where the electrode was
      placed. A statistically significant difference was found between the groups in
      body mass index, HbA1c, and in gestational age, but not in age or parity. Using
      the self-monitored blood glucose (SMBG), 88 % (7/8) of the NP and 54 % (13/24) of
      the NDP had no measurement above 6.7 mmol/l. However, 17 % (4/24) of the NDP and
      40 % (6/15) of the IGT showed more than two measurements above 6.7 mmol/l
      compared to 24 % (4/17) of the dietary-treated GDM. The differences between these
      groups were not significant (p = 0.21). The mean durations (+/- SD) of
      hyperglycemia above 6.7 mmol/l/24 h were: NP 111 +/- 120 min, NDP 138 +/- 120
      min, IGT 381.8 +/- 295 min, and GDM 190 +/- 155 min, p = 0.017; above 7.8
      mmol/l/24 h NP 24 +/- 49 min, NDP 38 +/- 47 min, IGT 170.7 +/- 190 min, and GDM
      64 +/- 88 min, p = 0.016; and above 8.9 mmol/l/24 h NP 9.3 +/- 25 min, NDP 7.5 +/
      14 min, IGT 59 +/- 77 min, and GDM 14 +/- 21 min, p = 0.026. There was no
      significant difference in the fetal outcome or rate of birth percentiles using
      the sensor data. CONCLUSIONS: The use of the sensor in pregnant women is
      unproblematic. a) The CGMS detected more frequent and longer durations of
      hyperglycemia in GDM compared to non-diabetic pregnant women than the SMBG. b)
      Women with an IGT exhibited higher glucose levels than patients with gestational
      diabetes. c) The clinical importance of these hyperglycemic intervals, e.g. with
      respect to the risk for macrosomia, must be assessed in larger trials.

PMID- 15578330
TI  - Coronary calcification in long-term type 1 diabetic patients -- a study with
      multi slice spiral computed tomography.
AB  - The risk for cardiovascular disease in diabetes is excessive. Multislice spiral
      computed tomography (MSCT) is a new technique for the assessment of coronary
      calcification in coronary artery disease. The aim of the study was to evaluate
      the presence of coronary calcium in asymptomatic long-term type 1 diabetic
      patients. Seventy-one type 1 diabetic patients (age 48 +/- 9 y, HbA1c 7.7 +/-
      1.2, BMI 24.4 +/- 2.8, duration of diabetes 26 +/- 9 y) without clinical evidence
      for coronary artery disease were assessed with MSCT. A volumetric score was used
      to calculate the coronary calcification (CC) score. Five cardiac reflex tests
      were performed to study patients for cardiac autonomic neuropathy. Coronary
      calcifications were detectable in 22 (31 %) type 1 diabetic patients (CC-score >
      0, mean CC-score 174 +/- 228 [X+/-SD]). Fourty-nine (69 %) type 1 diabetic
      patients demonstrated no coronary calcifications (CC-score= 0). In patients with
      coronary calcifications, both cardiac autonomic neuropathy and retinopathy were
      detected more frequently than in those without (64 % vs. 29 %, p < 0.02; 59 % vs.
      31 %; p < 0.02). Duration of diabetes was longer in patients with than without
      coronary calcification (32 +/- 10 y vs. 24 +/- 8 y, p < 0.01). Age, BMI, and
      HbA1c were not significantly different between patients with and without coronary
      calcification. The study demonstrates that nearly one third of asymptomatic long
      term type 1 diabetic patients present with coronary calcifications. In the
      patients, there is evidence for an association between coronary calcification and
      both cardiac autonomic neuropathy and retinopathy. MSCT is a promising non
      invasive approach to analyze early alterations of the coronary system in diabetic
      patients.

PMID- 15578331
TI  - High prevalence of peripheral arterial disease and low treatment rates in elderly
      primary care patients with diabetes.
AB  - Representative data on peripheral arterial disease (PAD) in community-based
      office practice are scarce while at the same time of high interest. Thus, we
      aimed to determine the prevalence of peripheral arterial disease (PAD),
      comorbidity of atherothrombotic manifestations, and treatment intensity among
      elderly diabetic patients in primary care. In this monitored cross-sectional
      study, 344 general practitioners throughout Germany determined the ankle-brachial
      index (ABI) of 6880 consecutive, unselected patients aged 65 years or older with
      bilateral Doppler ultrasound measurements. PAD was defined according to the
      recent American Heart Association guidelines (using the higher of the 2 systolic
      ankle pressures: ABI < 0.9) or peripheral revascularisation, or amputation
      because of PAD. Coronary events (CAD) and cerebrovascular events (CVD) were taken
      from the patient's history without additional diagnostic measures. Diabetes was
      defined according to the clinical diagnosis of the physician and/or HbA1c > or =
      6.5 % and/or intake of oral antidiabetic medication and/or application of
      insulin. 1.743 patients were classified as diabetics: the median disease duration
      was 6 years (1st; 3rd quartile: 2; 11), median HbA1c 6.6 % (5.9; 7.3), mean age
      72.5 +/- 5.4 years, and 51.4 % were females. Diabetics had in comparison with non
      diabetics a higher prevalence of PAD defined as ABI < 0.9 (26.3 % vs. 15.3 %,
      univariate odds ratio 2.0 [95 % confidence interval: 1.7; 2.3]), intermittent
      claudication (5.1 % vs. 2.1 %, OR: 2.5 [1.9; 3.4]), known CAD (16.1 % vs. 10.6 %,
      OR: 1.6 [1.4; 1.9]), and known CVD (6.8 % vs. 4.8 %; OR: 1.4 [1.2; 1.8]). 57.4 %
      of the diabetics with previously known PAD (as only atherothrombotic
      manifestation) received antiplatelet therapy (vs. 75.1 % with CAD and/or CVD
      only). The ABI was suitable as screening measure in the primary care setting. In
      elderly diabetics in comparison to non-diabetics, the prevalence of PAD was very
      high. Despite the known benefits of antiplatelet therapy, PAD patients were less
      intensively treated than patients with CAD or CVD.

PMID- 15578332
TI  - The carboxyterminal peptide of chorionic gonadotropin facilitates activation of
      the marmoset LH receptor.
AB  - Luteinizing hormone (LH) and chorionic gonadotropin (CG) are heterodimeric
      glycoprotein hormones acting on the luteinizing hormone receptor (LHR). In the
      LHR, which is genomically encoded by eleven exons, exon 10 encodes for the hinge
      region and its elimination impairs LH action, while CG maintains normal activity.
      The two gonadotropins differ in the carboxyterminal peptide (CTP) present in CG
      but absent in LH. Since the marmoset monkey (Callithrix jacchus) LHR naturally
      lacks exon 10 (LHR type II), we generated two recombinant marmoset gonadotropin
      preparations, one consisting of the wild type CG and one of truncated CG lacking
      the CTP (CG (-CTP)). After calibration in a mouse Leydig cell bioassay against
      the WHO LH80/522 standard, the ED (50) of the CG preparation on a COS7 cell line
      permanently expressing the marmoset LHR was 4.25 +/- 0.21 IU/L (n = 3).
      Stimulation of the COS7 cell line with equipotent concentrations of CG and CG (
      CTP) resulted in significantly different formation of cAMP (two-way ANOVA, p <
      0.001). In particular, cAMP production stimulated by CG (-CTP) was 3 - 4 times
      lower compared to CG at the saturating CG concentration (8 IU/L). We conclude,
      supplementing one current model of LHR activation, that exon 10 might play a
      permissive role in releasing the constraint of the receptor upon hormone binding,
      resulting in receptor activation. We speculate that, when exon 10 is lacking, the
      CTP can overcome its absence and facilitates the opening of the receptor,
      resulting in normal activation.

PMID- 15578333
TI  - Influence of hepatocyte-rich liver cell mixture and liver fibroblasts on
      prolonging graft islet survival in rats without immunosuppressive drugs.
AB  - BACKGROUND: We noted that a liver cell suspension, made up of a mixture of
      several kinds of hepatic cells, affected allogenic islet survival when it was
      transplanted into the liver, mixed with the islets or separately. AIM: To study
      if this effect was related to a liver cell mixture rich in hepatocytes (hp) or to
      liver fibroblasts (fb). METHODS: We studied 14 groups of rats: (A) a sham group
      with saline; (B) a group receiving transplantation with hepatic cells alone; (C)
      a control group, with islets alone via the portal vein, without hepatic cells (hp
      or fb). For the other groups, we used a different ratio of cells/islets (100 : 1,
      150 : 1 and 200 : 1) and different co-transplantation techniques with both types
      of cells. For the D, E, J groups, a mixture of hepatocytes (hepatocyte-rich liver
      cell mixture) or fibroblasts with islets was injected into the portal vein. For
      the other groups, we used a sequential procedure with a 15 minute interval
      between a first injection of hp or fb into the portal vein or into the vena cava,
      and a second injection of islets always into the portal vein; thus, it was a
      sequential portal/portal procedure with hepatocyte-rich liver cell mixture (hp)
      (F, G) or fibroblasts (K, L) and a sequential cava/portal with hp (H, I) or
      fibroblasts (M, N). RESULTS: Most of the co-transplantation groups showed
      functional islets (blood glucose < 250 mg/dl) on the first or second day of
      transplantation; after several days they once again had high glucose levels,
      though not as high as pre-transplantation. There was statistical significance (p
      < 0.001) between the presence or not of hepatic cells to obtain prolongation of
      graft survival (blood glucose < 250 mg/dl). Statistical significance (p < 0.001)
      was found for several sequential groups with hp (F, I) and fb (K, L). It was also
      remarkable that 3 rats (37.5 %) from the I group (sequential cava/portal with
      hp/islets 200 : 1) were euglycemic (blood glucose < 150 mg/dl) for more than 3
      months. ANOVA showed a large interaction between the type of transplant performed
      and the cellular ratio used, with a significance of p < 0.001. Histological
      studies in rats with prolonged euglycemia, showed insulin-producing cell
      aggregates in the liver, while there was a remarkable decrease in insulin
      producing cells in the remaining islets of pancreatic tissue. CONCLUSION: The
      results showed a marginal prolongation of islet graft survival when they are co
      transplanted with a hepatocyte-rich liver cell mixture or with liver fibroblasts.
      The mechanism does not seem to be a cellular interaction between different
      hepatic cells and islets, but some kind of cellular interaction or released
      factor from either two cell types on the immune system, blocking or modulating
      it, at least temporarily.

PMID- 15578334
TI  - Expression of gonadotropin-releasing hormone type-I (GnRH-I) and type-II (GnRH
      II) in human peripheral blood mononuclear cells (PMBCs) and regulation of B
      lymphoblastoid cell proliferation by GnRH-I and GnRH-II.
AB  - GnRH-I and its receptor (GnRHR-I) have previously been demonstrated and shown to
      be biologically active in the immune system, notably within T cells. Recently
      however a second form of GnRH (GnRH-II) has been described in the human. The
      function of both these neuropeptides in B lymphocytes has not previously been
      explored. The present study investigates GnRH-I and GnRH-II expression in human
      peripheral mononuclear blood cells (PMBCs) and B lymphoblastoid cells (B-LCLs),
      as well as their action in regulating B-LCL proliferation in the presence and
      absence of interleukin-2 (IL-2), both in GnRHR-I mutated lymphocytes and in a
      normal control. RT-PCR and immunocytochemistry identified locally produced GnRH-I
      and GnRH-II in all cell groups. Treatment of normal B-LCLs with GnRH-I (10 (-9) M
      and 10 (-5) M) or with interleukin-2 (IL-2) (50 IU/ml) resulted in a significant
      increase in cell proliferation compared with the untreated control. IL-2 and GnRH
      I (10 (-7) M, 10 (-6) M, 10 (-5) M) induced greater proliferation in normal B
      LCLs than IL-2 treatment alone. No significant proliferation occurred in GnRHR-I
      defective B-LCLs, in response to either GnRH-I (10 (-9) and 10 (-5) M) or IL-2
      treatment, nor to IL-2 and GnRH-I (10 (-10) to 10 (-5) M) co-treatment when
      compared to controls. Co-incubation of IL-2 and IL-2 + GnRH 10 (-5) M with a GnRH
      antagonist (Cetrorelix; 10 (-6) M) significantly attenuated the proliferation in
      normal B-LCLs. GnRH-II did not affect proliferation of normal B-LCLs alone, and
      did not alter the proliferative response to IL-2. Further investigation is
      required to clarify the physiological relevance of local GnRH-I/GnRH-II in immune
      system responsiveness.

PMID- 15578335
TI  - Vitamin B6 modulates glucocorticoid-dependent gene transcription in a promoter-
      and cell type-specific manner.
AB  - Due to their immunosuppressive effects, glucocorticoids (GC) are widely used in
      the treatment of inflammatory and autoimmune states. However, long-term GC
      treatment is associated with severe side effects. To increase the ratio of wanted
      and unwanted GC effects, is, therefore, a desirable goal, which could be achieved
      by either developing new "dissociating" GC or by combining conventional GC
      therapy with substances that selectively interfere with glucocorticoid receptor
      (GR) function. Vitamin B6 was previously shown to inhibit GR transactivation in
      non-immune cells. In the present study, we tested whether vitamin B6 would also
      interfere with GR function in immune cells and/or with transrepression in non
      immune cells. Normal human lymphocytes and Jurkat T lymphoma cells were
      transfected with luciferase reporter constructs under the control of the
      interleukin-2 (IL-2) and the leukemia inhibitory factor (LIF) promoter,
      respectively. Cells were stimulated with phorbol ester, ionomycin, and different
      concentrations of dexamethasone, either in the absence (a vitamin B6-free medium
      was especially prepared for this study) or presence of vitamin B6. Both promoters
      were strongly induced in response to phorbol ester and ionomycin. Dexamethasone
      inhibited this effect in a dose-dependent manner both in the presence and absence
      of vitamin B6. Similar results were obtained at the protein level (IL-2- and LIF
      specific ELISAs). Induction of a glucocorticoid response element (GRE)-driven
      promoter construct by dexamethasone in lymphoid cells was only marginally reduced
      by vitamin B6. In contrast, GR-mediated transactivation was strongly inhibited by
      vitamin B6 in HeLa cells, while GR-mediated transrepression of a matrix
      metalloproteinase 9 (MMP9) promoter construct was not affected. Our data indicate
      that vitamin B6 does not interfere with GC action in immune cells (wanted GC
      effects) while selectively inhibiting GR-dependent transactivation in non-immune
      cells (unwanted GC effects). Combination of GC treatment with supraphysiological
      doses of vitamin B6 may, thus, reduce the side effects of this type of
      immunosuppressive therapy, provided that the observed effects can be reproduced
      at subtoxic vitamin B6 concentrations in vivo.

PMID- 15578336
TI  - Radionuclide imaging metabolic activity of brown adipose tissue in a patient with
      pheochromocytoma.
AB  - We describe a patient with extra-adrenal pheochromocytoma and high plasma
      norepinephrine levels. Radionuclide images of this patient obtained using (18)F
      fluorodeoxyglucose and (123)I-metaiodobenzylguanidine revealed bilateral tracer
      accumulation in the shoulder and lower neck. The regions of radiotracer uptake
      corresponded to the location of human brown adipose tissue (BAT). Excessive
      sympathetic stimulation by high circulating catecholamine concentrations
      augmented the metabolic activity and tracer uptake in the BAT. This study showed
      that radionuclide imaging can noninvasively visualize human BAT in terms of
      metabolic and functional activity.

PMID- 15578337
TI  - Surgical outcome of endoscopic carpal tunnel release in 100 patients with carpal
      tunnel syndrome.
AB  - The purpose of this study is to present the surgical outcome of endoscopic carpal
      tunnel release (ECTR) for the treatment of carpal tunnel syndrome (CTS). One
      hundred and thirty-one procedures (36 right hands, 33 left hands and 31 bilateral
      hands) of single portal ECTR were performed upon 100 patients (age range: 36-77
      years, mean age: 52.9 years; 98 women and 2 men) with electrodiagnostically
      proven CTS for 2.5 years from 2001. Preoperative clinical severity and results of
      electrodiagnostic studies were compared with surgical outcomes at the minimal 3
      month postoperative period. Among 131 cases 125 (95.4 %) with complete or
      significant relief of symptoms were satisfied and 6 (4.6 %) with partial or no
      relief of symptoms were dissatisfied. There were 2 cases of major complications
      (one with ulnar nerve injury and the other with ulnar artery injury) that
      developed in our early experience of ECTR and 1 case of recurrence. The grade of
      electrodiagnostic abnormalities was associated with surgical outcome but there
      was no statistical significance between them. The severity of clinical findings,
      age at onset and symptom duration were not correlated with surgical outcome. In
      conclusion, ECTR surgery was effective in relieving the symptoms of CTS with a
      low complication rate after the learning curve period. Thus, ECTR can be an
      alternative to the traditional open surgery and can be the first procedure for
      CTS with several advantages over open methods.

PMID- 15578338
TI  - Image-guided robotic radiosurgery in a rat glioma model.
AB  - Despite the proven efficacy of radiosurgery for the treatment of brain tumors,
      limited histological information is available after treatment that might allow a
      better understanding of the relationship between radiation dose, the volume
      treated, and the response of the surrounding brain to the delivered radiation.
      The use of an animal model could provide the opportunity to clarify these
      relationships and answer several other key questions arising in clinical
      practice. We show here that treatment of small animals with radiosurgery is
      feasible using a robotically controlled linear accelerator, which offers the
      advantages of radiosurgery and preserves the potential for fractionated regimens
      without rigid immobilization. Specifically, we demonstrate the use of a
      robotically driven linear accelerator to provide radiosurgical treatment to a rat
      brain tumor model.

PMID- 15578339
TI  - Image-guided motor cortex stimulation in patients with central pain.
AB  - According to recent clinical data, motor cortex stimulation (MCS) is an
      alternative treatment for central pain syndromes. We present our minimally
      invasive technique of image guidance for the placement of the motor cortex
      stimulating electrode and assess the clinical usefulness of both neuronavigation
      and vacuum headrest. Five patients suffering from central pain underwent MCS with
      the guidance of a frameless stereotactic system (BrainLab AG, Munich, Germany).
      The neuronavigation was used for identification of the precentral gyrus and
      accurate planning of the single burr hole. The exact location was reconfirmed by
      an intraoperative stimulation test. Postoperative clinical and neuroradiological
      evaluations were performed in each patient. The navigation system worked properly
      in all 5 neurosurgical cases. Determination of the placement of stimulating
      electrode was possible in every case. All patients obtained postoperative pain
      relief. No surgical complication occurred, and the postoperative course was
      uneventful in all patients. This preliminary experience may confirm image
      guidance as a useful tool for the surgery of MCS. Additionally, minimal and safe
      exposure can be achieved using a single burr hole and vacuum headrest.

PMID- 15578340
TI  - Impact of neuronavigation and image-guided extensive resection for adult patients
      with supratentorial malignant astrocytomas: a single-institution retrospective
      study.
AB  - Neuronavigation has become an effective therapeutic modality and is used
      routinely for intra-axial tumor removal. This retrospective study was conducted
      to evaluate the clinical impact of neuronavigation and image-guided extensive
      resection for adult patients with supratentorial malignant astrocytomas. Between
      1990 and 2002, 76 adult patients with pathologically confirmed malignant
      astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical
      and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated
      using neuronavigation with conventional microneurosurgery and the other 34 were
      treated with conventional microneurosurgery alone. Postoperative early MRI with
      contrast enhancement was done, and gross total resection was defined as the
      complete absence of residual tumor. Survival time was analyzed with the Kaplan
      Meier method. Prognostic factors were obtained from the Cox proportional hazards
      model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80),
      use of neuronavigation, and gross total resection were significantly associated
      with longer survival. However, when the data were submitted to multivariate
      analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were
      independent prognostic factors. The median survival periods of patients receiving
      gross total resection (vs. partial resection) and neuronavigation (vs. no
      neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The
      percentage of a gross total resection was significantly higher in the
      neuronavigation group compared to that in the no-navigation group (64.3 % vs.
      38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in
      6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without
      neuronavigation, respectively, although this difference was not statistically
      significant. Our results showed that neuronavigation increases the radicality in
      the resection of malignant astrocytomas and is objectively useful for improving
      survival time.

PMID- 15578341
TI  - Functional neurosurgery in the MRI environment.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of
      microelectrode recording, electrical stimulation, and electrode position checking
      during functional neurosurgical procedures (DBS, lesion) in the interventional
      magnetic resonance imaging (iMRI) environment. METHODS: Seventy-six surgical
      procedures for DBS implant or radiofrequency lesion were performed in an open 0.2
      T MRI operating room. DBS implants were performed in 54 patients (72 surgical
      procedures) and unilateral radiofrequency lesions in three for a total of 76
      surgeries in 57 patients. Electrophysiological studies including macrostimulation
      and microelectrode recordings for localization were obtained in the 0.5 to 10 mT
      fringes of the magnetic field in 51 surgeries. MRI confirmation of the electrode
      position during the procedure was performed after electrophysiological
      localization. RESULTS: The magnetic field associated with the MRI scanner did not
      contribute significant noise to microelectrode recordings. Anatomical
      confirmation of electrode position was possible within the MRI artifact from the
      DBS hardware. Symptomatic hemorrhage was detected in two (2.6 %) patients during
      the operation. Image quality of the 0.2 T MRI scan was sub-optimal for anatomical
      localization. However, image fusion with pre-operative scans permitted excellent
      visualization of the DBS electrode tip in relation to the higher quality 1.5 T
      MRI anatomical scans. CONCLUSION: This study shows that conventional stereotactic
      localization, microelectrode recordings, electrical stimulation, implant of DBS
      hardware, and radiofrequency lesion placement are possible in the open 0.2 T iMRI
      environment. The convenience of having an imaging modality that can visualize the
      brain during the operation is ideal for stereotactic procedures.

PMID- 15578342
TI  - CyberKnife radiosurgery for vestibular schwannoma.
AB  - OBJECTIVE: The CyberKnife is newly developed equipment for radiosurgery and
      fractionated radiosurgery. The authors report on their experience using the
      CyberKnife in 38 patients with vestibular schwannoma who were treated between
      1998 to 2002. METHODS: During this period, 38 patients with vestibular schwannoma
      were treated using CyberKnife fractionated radiosurgery. Before undergoing
      fractionated radiosurgery, 14 patients had Gardner Robertson classes I or II
      hearing (the serviceable hearing group), and 24 patients had classes III to V
      hearing (the non-serviceable hearing group). The treatment volumes of these two
      groups were 0.5 to 24.0 cm (3) (mean 4.7 cm (3)), and 0.5 to 41.6 cm (3) (mean
      8.2 cm (3)). Target irradiation was administered in 1 - 3 fractions (mean 2.5
      fractions). The total marginal radiation doses were 15.0 to 20.5 Gy (mean 17.0
      Gy), and 11.9 to 20.1 Gy (mean 16.9 Gy), respectively. RESULTS: After a mean
      follow-up period of 31.9 months (range 12 to 59 months, median 27 months), 94 %
      of the tumors were controlled. Only one patient in the group with non-serviceable
      hearing underwent additional surgical resection for a presumed increase in tumor
      size. The hearing preservation rate was 93 %. Facial weakness did not develop in
      any of the patients in the serviceable hearing group. New trigeminal symptoms did
      not develop in any patients in either group. CONCLUSION: Although a longer and
      more extensive follow-up is needed, CyberKnife fractionated radiosurgery is
      considered to be safe and effective, even in patients with large tumors.

PMID- 15578343
TI  - Combined minimal invasive techniques in deep supratentorial intracerebral
      haematomas.
AB  - Minimal invasive techniques (MIT) like microscopy, stereotaxy, endoscopy and
      neuronavigation facilitate and improve neurosurgical results and reduce the
      operative trauma. We report the combined employment of these techniques and the
      results obtained in our department during the last 7 years in 95 consecutive
      patients with supratentorial deep located intracerebral haematomas (ICHs). Thirty
      six deteriorating patients with deep ICHs under 30 cm (3) volume associated to
      intraventricular bleeding, were treated early (first 24 hours after bleeding)
      with neuronavigation guided stereotactic lysis, using multiplanar targets (1 to
      3). Microsurgical clot aspiration through an enlarged burr-hole was frequently
      combined with endoscope- or neuronavigation-assisted evacuation within the first
      6 hours after bleeding for the rest of the deteriorating patients with ICHs
      larger than 30 cm (3). A 1.2 cm narrow surgical corridor assured the least injury
      to vital cortical areas, tracts and blood vessels. In 86 cases the clots were
      adequately removed (non-measurable rest) with a reduced morbid mortality (13.8
      and 8.6 as well as 23.3 and 16.9 for stereotactic and microscopic MIT,
      respectively). In our experience, the use of combined MIT adapted to the surgical
      urgency of the individual patient reduces the operative trauma and improves the
      accuracy for the access to the clot allowing an adequate haematoma evacuation and
      a satisfactory outcome in most of the cases.

PMID- 15578344
TI  - Preoperative embolization of intracranial meningiomas with Embosphere
      microspheres.
AB  - BACKGROUND: To reduce intraoperative bleeding and to facilitate surgery by
      inducing tumor softening, a preoperative embolization of meningiomas is commonly
      recommended. PATIENTS AND METHODS: We report on our experience with non
      resorbable microspheres (Embosphere) in the preoperative endovascular
      embolization of 17 intracranial meningiomas. After adding contrast media to the
      particles sized 40-500 micron, the embolization process was followed under
      fluoroscopy. There was a good passage of microcatheters if high concentrations of
      particles were avoided. RESULTS: The obstruction of the tumor feeders by
      particles was accompanied by a regression of tumor blush in DSA. CT controls
      showed a diminished contrast accumulation of the tumors already 1-2 days after
      embolization. Histologically, Embosphere microspheres were easy detectable with
      all commonly used staining methods. Embolization triggered, microscopically
      detectable necrosis was found in 77 % of the tumors. The mean interval between
      embolization and tumor extirpation was 2.5 days. The average time required for
      tumor extirpation was 244 minutes, while the average blood loss was 749 ml.
      CONCLUSIONS: Our experiences show that Embosphere microspheres are effective
      embolic agents in obstructing meningeal feeders of preoperatively treated
      meningiomas.

PMID- 15578345
TI  - Relationship between anterior inferior cerebellar artery and facial
      vestibulocochlear nerve complex: an anatomical and magnetic resonance images
      correlation study.
AB  - For the successful microneurosurgical treatment of CP angle located pathologies,
      an understanding of the relationship and variations between neural and vascular
      structures and a certain diagnosis are the most valuable factors for surgeons. CP
      angle lesions have now become a visible area by advances in magnetic resonance
      imaging (MRI) technology. An evaluation of this area and the decision for a
      neurosurgical decompression procedure are easier than before. Twenty unfixed
      adult human cadaver specimens, that have no sign of central nervous system
      pathology, were obtained and dissected bilaterally at routine autopsy. The facial
      vestibulocochlear (VII - VIIIth) nerve complex and the anterior inferior
      cerebellar artery (AICA) were identified in all specimens. Thirteen of the 40
      (32.5 %) AICA were situated ventrally and fourteen (35 %) were located dorsally
      to the VII - VIIIth nerve complex. Thirteen (32.5 %) passed between the VIIth and
      the VIIIth nerve fibers. Five of the 40 (12.5 %) AICA had a loop near the nerve
      complex and then passed the nerves ventrally or dorsally. In an MRI study 74
      adult persons (148 sides) were investigated by using three-dimensional Fourier
      transformation constructive interference in the steady state technique (3D FT
      CISS) on a 1.5 Tesla MRI system (Siemens Magnetom, Erlangen, Germany). The
      results were as follows; 48 AICA (32.4 % of all 148 AICA) were situated ventrally
      to the VII-VIIIth nerve complex, 45 AICA (30.4 %) were situated dorsally to the
      VII-VIIIth nerve complex, and the AICA passed between the VIIth and VIIIth nerves
      in 51 samples (34.5 %). In four of the 148 CP angles (2.7 %), the AICA was not
      identified. There was an AICA loop coursing to the internal acoustic meatus in 15
      patients (10.1 %). In this study, we examined the relations between VIIth and
      VIIIth nerve complex and the AICA in cadaver and MRI materials for an
      understanding of the value and reliability of the radiological data. This study
      also shows the anatomical variation between these structures.

PMID- 15578346
TI  - A neuroendoscopic approach to the aqueduct via the fourth ventricle combined with
      suboccipital craniectomy.
AB  - OBJECTIVES: We have tried to approach the aqueduct less invasively with the
      endoscope in combination with a small suboccipital craniectomy, especially for
      lesions of the aqueduct close to the fourth ventricle. METHODS: The patient is
      placed in the prone position and a small suboccipital craniectomy is performed.
      After elevating the bilateral tonsils with retractors, the sheath of the
      endoscope is inserted from a small skin incision made on the posterior midline of
      the neck, far from the craniectomy site. The skin incision for endoscopic
      insertion is planned on the linear extension connecting the aqueduct and the
      foramen of Magendi on the craniocervical MRI. A rigid endoscope is inserted
      through the fourth ventricle to the aqueduct for exploration and surgical
      manipulation. RESULTS: Two cases with hydrocephalus due to aqueductal stenosis,
      with gait disturbance were operated. After exploration of the aqueduct via the
      fourth ventricle, endoscopic aqueductal plasty was performed. The postoperative
      courses were uneventful. The patients' symptoms disappeared. CONCLUSIONS: This
      approach can be applied for less invasive endoscopic exploration and surgery
      around the aqueduct close to the fourth ventricle with a rigid endoscope, without
      overflexion of the neck, or a large craniectomy, or overretraction of the
      tonsils, or incision of the inferior vermis.

PMID- 15578347
TI  - Bipolar microscissors.
AB  - The authors present a novel bipolar-coagulation microscissors exclusively
      designed for microsurgical use which can be applied easily, safely and
      effectively. The device is particularly helpful in the management (coagulation
      and cutting) of cerebral microvessels during the resection of brain tumors rich
      in vascularity or AVMs. The advantages of the instrument are the avoidance of
      exchanges of bipolar and microscissors under the microscope, reduction of fatigue
      for the operator, and decreases of operative time and blood loss while still
      achieving a good result.

PMID- 15578348
TI  - Posterior endoscopic lumbar discectomy using a thoracoport as a tubular
      retractor.
AB  - OBJECTIVE: To make lumbar discectomy simple and feasible, we developed an
      endoscopic surgical technique that uses a Thoracoport as a tubular retractor.
      SURGICAL TECHNIQUE: The patient was placed in a 60-degree forwardly inclined
      lateral position with the side of the lesion on the top. After radiological
      confirmation of the index level, a Thoracoport was inserted through a 2-cm
      paramedian transverse skin incision. A 0-degree rod lens endoscope was mounted to
      a scope holder and placed into the retractor for magnification and illumination.
      Laminotomy was performed with a high-speed drill to reach the insertion of the
      yellow ligament to the upper lamina. A 2-mm undercutting of the upper facet was
      performed with a punch to expose the lateral edge of the nerve root. Surgical
      instruments were inserted next to the endoscope for manipulation. The herniated
      disc was identified and removed with pituitary rongeurs as in a standard
      microdiscectomy. With this technique, a sufficient amount of bone is resected to
      expose the disc lateral to the nerve root; hemostasis is easily achieved and the
      incidence of nerve root injury is reduced. CONCLUSION: We have successfully
      performed an endoscopic lumbar discectomy in 20 patients by using a Thoracoport
      as a tubular retractor. No specially designed instruments were required. This
      technique was a safe and effective minimally invasive approach to treating lumbar
      disc disease according to our preliminary experience.

PMID- 15578349
TI  - Predictors of positive tuberculin skin test (TST) results after 2-step TST among
      health care workers in Manitoba, Canada.
AB  - BACKGROUND: Baseline 2-step tuberculin skin testing (TST) is recommended for
      health care workers (HCWs) to identify cases of the "boosting phenomenon" (i.e.,
      a negative initial TST result followed by a positive result) and to track the
      risk of acquiring occupational tuberculosis. However, the 2-step TST has been
      shown to be insufficient to identify all cases of the booster phenomenon in older
      adults and refugees. The objective of this study was to identify whether a
      history of bacille Calmette-Guerin (BCG) vaccination and foreign birth--variables
      that are known to be associated with the booster phenomenon--remain predictors of
      a positive TST result in a group of HCWs documented to have negative 2-step TST
      results (i.e., 2 TSTs done 7-28 days apart with indurations <10 mm in diameter).
      METHODS: We performed a retrospective analysis of an employee database in a
      tertiary care hospital in Winnipeg, Canada. The study population was comprised of
      698 HCWs with negative 2-step TST results who underwent a TST 0-2 years after
      completion of the 2-step procedure. RESULTS: Forty-six HCWs (6.6%) had a positive
      TST result 0-2 years after the 2-step test. In a multiple logistic regression
      analysis controlling for age, BCG vaccination, foreign birth, sex, and work
      setting, only history of BCG vaccination (odds ratio [OR], 8.38; 95% confidence
      interval [CI], 4.04-17.4), foreign birth (OR, 3.19; 95% CI, 1.53-6.62), and high
      risk work setting (OR, 2.93; 95% CI, 1.44-5.95) were associated with a positive
      TST result. CONCLUSIONS: Even for HCWs with negative results of 2-step TST,
      foreign birth and history of BCG vaccination are associated with a positive
      result of a future TST. Some positive TST results in such HCWs are related to
      nonoccupational factors, including delayed boosting, rather than to conversion
      due to recent tuberculosis contact.

PMID- 15578350
TI  - Pharmacokinetics of enfuvirtide in a patient with impaired renal function.
AB  - Enfuvirtide is the first member of the fourth class of antiretroviral drugs to
      become available. We present a case report of a human immunodeficiency virus
      (HIV)-positive patient with mild renal impairment who developed severe renal
      impairment secondary to tenofovir therapy while receiving enfuvirtide. Because
      the patient's pharmacokinetic profile was not significantly altered, compared
      with that of HIV-infected patients with normal renal function, no dose
      modifications were required.

PMID- 15578351
TI  - A novel use for drotrecogin alfa (activated): successful treatment of septic
      shock associated with coccidioidomycosis.
AB  - We present 2 cases of septic shock associated with coccidioidomycosis that were
      successfully treated with drotrecogin alfa (activated) in combination with
      antifungal agents. The favorable outcomes, in light of the high mortality usually
      associated with this condition, suggest that drotrecogin alfa (activated) may be
      a valuable adjunct for treating septic shock due to endemic mycoses.

PMID- 15578352
TI  - Efficacy and safety of caspofungin for treatment of invasive aspergillosis in
      patients refractory to or intolerant of conventional antifungal therapy.
AB  - BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and
      mortality among immunocompromised patients. Echinocandins are novel antifungal
      molecules with in vitro and in vivo activity against Aspergillus species.
      METHODS: We investigated the efficacy and safety of caspofungin in the treatment
      of IA. Ninety patients with IA who were refractory to or intolerant of
      amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled
      to receive caspofungin. RESULTS: Efficacy was assessed for 83 patients who had
      infection consistent with definitions of IA and who received >or=1 dose of study
      drug. Common underlying conditions included hematologic malignancy (48% of
      patients), allogeneic blood and marrow transplantation (25% of patients), and
      solid-organ transplantation (11% of patients). Seventy-one patients (86%) were
      refractory to and 12 patients (14%) were intolerant of previous therapy. A
      favorable response to caspofungin therapy was observed in 37 (45%) of 83
      patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13
      with disseminated aspergillosis. Two patients discontinued caspofungin therapy
      because of drug-related adverse events. Drug-related nephrotoxicity and
      hepatotoxicity occurred infrequently. CONCLUSION: Caspofungin demonstrated
      usefulness in the salvage treatment of IA.

PMID- 15578353
TI  - Societal costs and morbidity of pertussis in adolescents and adults.
AB  - BACKGROUND: Since the 1980s, the reported incidence of pertussis among
      adolescents and adults has been steadily increasing. To understand whether the
      benefits of an acellular pertussis vaccine formulated for adolescents and adults
      might offset its costs, policy makers will need information about morbidity and
      societal (medical and nonmedical) costs of pertussis. METHODS: Adolescents (age,
      10-17 years) and adults (age, >or=18 years) with confirmed pertussis illness were
      identified by the Massachusetts enhanced pertussis surveillance system. We
      evaluated medical costs in a cohort of patients who had confirmed pertussis
      during the period of January 1998 through December 2000; nonmedical costs, by
      means of prospective interviews, in a cohort of patients who had confirmed
      pertussis during the period of December 2001 through January 2003; and morbidity
      in both cohorts. Our main outcome measures were mean costs per case, in 2002 US
      dollars. RESULTS: In the analysis of medical costs, 1679 adolescents and 936
      adults were found to have mean costs of 242 dollars and 326 dollars, respectively
      (P<.05). In interviews with 314 adolescents and 203 adults, adults had
      significantly higher nonmedical costs (447 dollars) than those of adolescents
      (155 dollars). A total of 83% of adolescents missed a mean of 5.5 days from
      school (range, 0.4-32 days), and 61% of adults missed a mean of 9.8 days from
      work (range, 0.1-180 days) because of pertussis. Thirty-eight percent of
      adolescents and 61% of adults were still coughing at the time of the interview,
      which occurred an average of 106 days and 94 days, respectively, after cough
      onset. CONCLUSIONS: Pertussis causes significant morbidity in and costs for
      adolescents and adults, with time losses comprising the largest proportion of the
      cost. Societal costs should be considered when making decisions about potential
      vaccine use in the future.

PMID- 15578354
TI  - The 100-day cough: the time for prevention has arrived.

PMID- 15578355
TI  - Evaluation of reported malaria chemoprophylactic failure among travelers in a US
      University Exchange Program, 2002.
AB  - BACKGROUND: Travelers to malarious areas are at risk of acquiring malaria;
      however, with chemoprophylaxis and prompt, effective therapy, serious
      complications of infection are generally preventable. In June 2002, we
      investigated a report of a cluster of malaria cases among US university staff and
      students who visited Ghana and were reportedly adherent to appropriate malaria
      chemoprophylaxis. METHODS: We administered a questionnaire to all participants
      and collected blood specimens for malaria serological examinations from those
      reporting malaria infection diagnosed by blood smear in Ghana. RESULTS: Of the 33
      participants, 25 completed the questionnaire. Twenty-four took a Centers for
      Disease Control and Prevention-recommended chemoprophylactic drug; 14 (56%) of 25
      reported complete adherence to therapy. Twenty (80%) of 25 subjects reported
      symptoms consistent with possible malaria. Six of these persons reported a
      microscopic diagnosis of malaria and were treated in Ghana. Serological
      examination for malaria was performed using blood samples obtained from 5 of
      these participants; the results for all were negative, suggesting that incorrect
      diagnoses of malaria were made. CONCLUSIONS: Misdiagnosis of malaria made while a
      person is abroad may not only lead to erroneous reports of drug resistance, but
      it could also result in unnecessary administration of antimalarial treatment.
      Health care providers and public health authorities must critically evaluate
      reports of chemoprophylactic failures and disseminate accurate information to
      travelers.

PMID- 15578356
TI  - The sound of hoof beats does not always mean that it is a zebra.

PMID- 15578357
TI  - Clinical features and predictors of diphtheritic cardiomyopathy in Vietnamese
      children.
AB  - BACKGROUND: Despite the availability of antitoxin and antibiotics, the mortality
      rate for diphtheria remains high, mostly because of cardiac complications.
      METHODS: During 1 year, 154 Vietnamese children with diphtheria admitted to a
      referral hospital were studied prospectively with clinical examination, including
      a simple pseudomembrane score, 12-lead and 24-hour electrocardiography,
      measurement of serum cardiac enzyme levels, and estimation of troponin T levels.
      RESULTS: Thirteen children had diphtheritic cardiomyopathy on admission, and 19
      developed it subsequently. Twelve children (8%) died. The combination of
      pseudomembrane score of >2 and bull neck predicted the development of
      diphtheritic cardiomyopathy, with a positive predictive value of 83% and a
      negative predictive value of 93%. Administration of 24-hour electrocardiography
      on admission improved the ability to predict diphtheritic cardiomyopathy by 57%.
      Fatal outcome was best predicted by the combination of myocarditis on admission
      and a pseudomembrane score of >2. Of the cardiac enzyme levels measured, an
      elevated aspartate aminotransferase level was the best predictor. The presence of
      troponin T identified additional children with subclinical cardiac damage.
      CONCLUSIONS: The development of diphtheritic cardiomyopathy can be predicted by
      means of simple measures.

PMID- 15578358
TI  - Is "aseptic" loosening of the prosthetic cup after total hip replacement due to
      nonculturable bacterial pathogens in patients with low-grade infection?
AB  - BACKGROUND: Loosening of the prosthetic cup is the limiting factor in the service
      life of total hip prostheses (THPs). Despite effective culture methods, the
      detection of low-grade infection in patients with loose implants still presents a
      challenge. It is crucial to distinguish between "aseptic" loosening and loosening
      due to periprosthetic infection, so that appropriate treatment can be
      administered. We investigated whether aseptic loosening of the acetabular
      components of THPs is due to unrecognized infection. METHODS: From October
      through December 2002, a total of 24 patients with acetabular cup loosening were
      investigated. Only patients without clinical signs of infection and with negative
      results of bacteriologic culture of synovial fluid (obtained by preoperative
      aspiration) were included in the study. Intraoperative biopsy samples obtained
      from the neocapsule and synovia (e.g., the interface membrane) were examined by
      means of routine culture methods and by polymerase chain reaction (PCR) for
      detection of 16S ribosomal RNA (rRNA). Control subjects included 9 patients
      undergoing primary hip arthroplasty. RESULTS: C-reactive protein levels and
      erythrocyte sedimentation rates were slightly elevated in the group with
      loosening, compared with the control group, but the difference was not
      statistically significant. PCR and routine culture showed no microorganisms in
      either group, with the exception of 1 patient in the loosening group.
      CONCLUSIONS: PCR for detection of 16S rRNA in tissue specimens obtained from hip
      joints is not superior to routine bacteriologic culture techniques for detection
      of low-grade infections. However, these results demonstrate that the loosening of
      cups in THPs do not usually result from nonculturable periprosthetic infection,
      if the microbiological processing is adequate.

PMID- 15578359
TI  - Reducing major cause-specific hospitalization rates and shortening hospital stays
      after influenza vaccination.
AB  - BACKGROUND: The impact of influenza vaccination on major cause-specific
      hospitalization and the duration of hospital stay is rarely reported. Our purpose
      was to study the effect of vaccine efficacy on major disease-specific
      hospitalization and the duration of hospital stays among elderly persons.
      SUBJECTS AND METHODS: From 1 January through 30 June 2001, we prospectively
      observed 35,637 vaccinated elderly persons (age, >or=65 years) and 53,094
      unvaccinated elderly persons in Kaohsiung County, Taiwan, by computerized linkage
      to the National Health Insurance database. Of these persons, 21,347 had been
      assigned a high-risk status by the Department of Health, Taiwan. Univariate and
      multivariate logistic regression were used for determining vaccine efficacy in
      hospitalization. Multiple linear regression analyses were performed for
      determining the length of hospital stays. RESULTS: In both high-risk and low-risk
      groups, vaccination was associated with reducing the rates of hospitalization for
      all causes (20% vs. 23%), lung diseases, congestive heart failure (43% vs. 32%),
      renal disease, and liver disease (P<.05). It was also significant for stroke,
      hypertension, diabetes, neoplasm, and injury in low-risk patients (P<.05).
      Multivariate logistic regression showed that vaccination was significantly
      associated with reducing the rate of hospitalization (odds ratio [OR], 0.89; 95%
      confidence interval [CI], 0.86-0.92), but those with high-risk status had an
      increased risk of hospitalization (OR, 3.69; 95% CI, 3.56-3.82). Multiple linear
      regression analysis showed that vaccination decreased the duration of all-cause
      hospital stays (coefficient, -2.4 days; 95% CI, -2.7 to -2.1 days) and of
      hospitalization due to lung disease (coefficient, -4.9 days; 95% CI, -6.0 to -3.8
      days). CONCLUSION: Influenza vaccination may reduce hospitalization rates and
      shorten hospital stays not only for lung diseases but also for other common
      diseases in high-risk and low-risk elderly populations.

PMID- 15578360
TI  - Influenza-associated mortality in Hong Kong.
AB  - BACKGROUND: The impact of influenza on mortality in countries in subtropical and
      tropical regions is poorly quantified. Estimation of influenza-related illness in
      warm-climate regions is more difficult, because the seasonality of virus
      circulation is less well-defined. Partly as a result of these factors, influenza
      vaccine is grossly underutilized in the tropics, even for individuals >or=65
      years of age. METHODS: Weekly numbers of deaths were modeled by Poisson
      regression, and excess deaths attributable to influenza in Hong Kong were
      estimated for 1996-1999. Comparison of weekly mortality during periods of
      influenza predominance and periods of low influenza activity was used to derive
      an alternative estimate of influenza-associated mortality. RESULTS: Estimates
      derived from the Poisson model indicated that influenza resulted in 7.3 deaths
      per 100,000 population per year (95% confidence interval [CI], 3.1-11.4) from
      cardiorespiratory disease among individuals aged 40-65 years and 102.0 deaths per
      100,000 per population per year (95% CI, 61.2-142.7) among individuals aged
      >or=65 years. Although respiratory diseases accounted for the majority of
      influenza-related deaths, influenza also contributed to 13.8% (95% CI, 4.8%-
      22.7%) and 5.3% (95% CI, 1.2%-9.3%) of deaths related to ischemic heart disease.
      CONCLUSION: Influenza is associated with deaths due to ischemic heart disease as
      well from respiratory diseases. Overall influenza-associated mortality in a
      region with a warm climate, such as Hong Kong, is comparable with that documented
      in temperate regions. The need for influenza vaccination in tropical regions
      needs to be reassessed.

PMID- 15578361
TI  - Treatment of schistosomal myeloradiculopathy with praziquantel and
      corticosteroids and evaluation by magnetic resonance imaging: a longitudinal
      study.
AB  - BACKGROUND: The best treatment for schistosomal myeloradiculopathy (SMR) remains
      undefined. There is also no longitudinal study to estimate the value of magnetic
      resonance imaging (MRI) in the diagnosis and follow-up of this disease. METHODS:
      Patients with the following presentation were considered for study: lumbar and/or
      lower limb pain; lower limb weakness; anesthesia, hypoesthesia, or paresthesia;
      bladder and/or intestinal dysfunction; and sexual impotence. Sixteen patients
      with SMR were treated with oral praziquantel (50 mg/kg in a single dose) and
      methylprednisolone (15 mg/kg/day intravenously for 5 days) followed by prednisone
      (1 mg/kg/day orally for 6 months). Clinical outcome was prospectively evaluated
      in months 2 and 6 of treatment. RESULTS: Image alterations were detected by MRI
      at diagnosis for all patients, and normalization or improvement was reported at
      the end of treatment. There was statistically significant clinical melioration at
      both the second and sixth months of therapy for most neurological alterations.
      However, the best clinical outcome was achieved when the steroid was given for >2
      months. CONCLUSIONS: Treatment with praziquantel associated with corticosteroids
      was successful in all cases. MRI proved to be a good method for the diagnosis of
      SMR and helpful in the evaluation of response to treatment.

PMID- 15578362
TI  - Prevention of peritransplantation viridans streptococcal bacteremia with early
      vancomycin administration: a single-center observational cohort study.
AB  - BACKGROUND: Viridans streptococcal bacteremia (VSB) after allogeneic
      hematopoietic stem cell transplantation (HSCT) is associated with substantial
      mortality. Prevention of this serious complication is therefore a high priority.
      The objective of this study was to evaluate the effect of early vancomycin
      administration on rates and outcomes of VSB. METHODS: We analyzed the effect of
      early vancomycin on the incidence of VSB in a cohort of 430 consecutive HSCTs
      performed during the period of 1 January 1998 to 30 September 2002. The primary
      end point was time to diagnosis of VSB. Early vancomycin was defined as >or=2
      doses of vancomycin between days -7 through +7 after HSCT or diagnosis of VSB,
      whichever occurred first. Risk factors for VSB were identified in univariate and
      multivariate Cox proportional hazard models. RESULTS: The incidence of VSB in the
      cohort was 7.4%. The incidence of VSB in patients who did not receive early
      vancomycin was 24.8%, compared with 0.3% in patients who did (P<.001). Additional
      risk factors were female sex, conditioning with total body irradiation, and
      diagnosis of chronic myelogenous leukemia. CONCLUSIONS: The attributable
      mortality rate for VSB in our cohort was 21%. Early vancomycin was associated
      with decreased VSB (hazard ratio, 0.02; 95% confidence interval, 0.003-0.19)
      after controlling for age, sex, underlying disease, and transplantation
      variables. The benefits of vancomycin prophylaxis for the prevention of VSB and
      associated mortality need to be evaluated in a prospective clinical trial.

PMID- 15578363
TI  - High rate of varicella complications among Mexican-born adults in Alabama.
AB  - OBJECTIVE: Our study examines risk factors for severe varicella in an outbreak
      among Mexican-born adults, and it compares susceptibility to infection and
      reliability of self-reported varicella history for these individuals with that
      for adults born in the United States in the outbreak locale, which may guide
      vaccination strategies. METHODS: We interviewed case patients and non-case
      persons in the affected apartment complex and workplace, assessed disease history
      and susceptibility by testing for varicella-zoster virus immunoglobulin G
      antibodies, and reviewed the clinical data of case patients. RESULTS: Five of 18
      case patients had serious complications for which they sought medical care; 1 was
      hospitalized for pneumonia, and 1 was hospitalized for Guillain-Barre syndrome.
      Only intense exposure (e.g., sharing a bed) was marginally associated with severe
      disease (P=.08). In the workplace, varicella susceptibility was higher among
      Mexican-born workers (20%) than among workers born in the United States (3%)
      (adjusted prevalence odds ratio, 5.4; 95% confidence interval, 2.3-14.8). Mexican
      born persons had the highest positive predictive value of self-reported disease
      (100%) in predicting immunity, and those born in the United States had the lowest
      negative predictive value of self-reported history (10%) in predicting
      susceptibility. CONCLUSIONS: Varicella is a more serious disease among adults
      than among children, and Mexican-born adults living in the United States might
      have a higher risk of acquiring varicella than US-born adults. Varicella
      outbreaks involving adults should be prioritized for control efforts. Outbreaks
      can be prevented by vaccinating susceptible adults.

PMID- 15578364
TI  - Varicella vaccine for susceptible adults: do it today.

PMID- 15578365
TI  - The burden of community-acquired pneumonia in seniors: results of a population
      based study.
AB  - BACKGROUND: Pneumonia is recognized as a leading cause of morbidity in seniors.
      However, the overall burden of this disease--and, in particular, the contribution
      of ambulatory cases to that burden--is not well defined. To estimate rates of
      community-acquired pneumonia and to identify risk factors for this disease, we
      conducted a large, population-based cohort study of persons aged >or=65 years
      that included both hospitalizations and outpatient visits for pneumonia. METHODS:
      The study population consisted of 46,237 seniors enrolled at Group Health
      Cooperative who were observed over a 3-year period. Pneumonia episodes
      presumptively identified by International Classification of Diseases, Ninth
      Revision, Clinical Modification codes assigned to medical encounters were
      validated by medical record review. Characteristics of participants were defined
      by administrative data sources. RESULTS: The overall rate of community-acquired
      pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65-69
      years to 52.3 cases per 1000 person-years among those aged >or=85 years. In this
      population, 59.3% of all pneumonia episodes were treated on an outpatient basis.
      In multivariate analysis, risk factors for community-acquired pneumonia included
      age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus,
      congestive heart failure, and smoking. CONCLUSIONS: On the basis of these data,
      we estimate that roughly 915,900 cases of community-acquired pneumonia occur
      annually among seniors in the United States and that approximately 1 of every 20
      persons aged >or=85 years will have a new episode of community-acquired pneumonia
      each year.

PMID- 15578366
TI  - Use of population-based cohort data to assess community-acquired pneumonia: a
      powerful approach.

PMID- 15578367
TI  - Pyogenic liver abscess: recent trends in etiology and mortality.
AB  - BACKGROUND: Pyogenic liver abscess, a potentially life-threatening disease, has
      undergone significant changes in epidemiology, management, and mortality over the
      past several decades. METHODS: We reviewed the data for patients admitted to
      Bellevue Hospital and New York University Downtown Hospital (New York, New York)
      over a 10-year period. RESULTS: Of 79 cases reviewed, 43% occurred in patients
      with underlying biliary disease. The most common symptoms were fever, chills, and
      right upper quadrant pain or tenderness. The most common laboratory abnormalities
      were an elevated white blood cell count (in 68% of cases), temperature >or=38.1
      degrees C (90%), a low albumin level (70.2%), and an elevated alkaline
      phosphatase level (67%). Seventy percent of the abscesses were in the right lobe,
      and 77% were solitary. Klebsiella pneumoniae was identified in 41% of cases in
      which a pathogen was recovered. Eighteen (50%) of 36 Asian patients had K.
      pneumoniae isolated, in contrast to 6 (27.3%) of 22 non-Asian patients (not
      statistically significant). Fifty-six percent of cases involved treatment with
      percutaneous drainage. Although prior reports noted mortality of 11%-31%, we
      observed only 2 deaths (mortality, 2.5%). CONCLUSIONS: The data suggest that K.
      pneumoniae has become the predominant etiology of pyogenic liver abscess and that
      mortality from this disease has decreased substantially.

PMID- 15578368
TI  - Superinfection following smallpox vaccination (Vaccinia), United States:
      surveillance January 2003 through January 2004.
AB  - BACKGROUND: Superinfection is an adverse event following smallpox vaccination.
      The clinical presentation is similar to that of a large normal vaccine reaction
      or "robust take," and the frequency is unknown. METHODS: We retrospectively
      reviewed all reported severe local reactions consistent with superinfection among
      United States civilian smallpox vaccinees from January 2003 through January 2004.
      We applied a standard case definition and estimated the frequency of
      superinfection following smallpox vaccination. RESULTS: We identified 48 reported
      cases for further review among 39,350 [corrected] smallpox vaccinees. Two (4%) of
      the 48 reported cases met the case definition for superinfection; neither of the
      patients had a pathogenic organism isolated from their infection site. Both were
      treated with antibiotics and resolved their infection. Of the 46 cases determined
      not to be superinfection, 41 (89%) were temporally consistent with a large normal
      vaccine reaction. Thirty (75%) of 40 reported case patients for whom data were
      available received antibiotic therapy. CONCLUSIONS: Superinfection following
      smallpox vaccination is rare. Most of the reported superinfection cases were
      probably large normal smallpox vaccine reactions. Educating providers about the
      normal response to smallpox vaccine may decrease the overdiagnosis of
      superinfection and the unnecessary use of antimicrobials.

PMID- 15578369
TI  - Rethinking smallpox.
AB  - The potential consequences of a competently executed smallpox attack have not
      been adequately considered by policy makers. The possibility of release of an
      aerosolized and/or bioengineered virus must be anticipated and planned for. The
      transmission and infectivity of variola virus are examined. Arguments for and
      against pre-event vaccination are offered. The likely morbidity and mortality
      that would ensue from implementation of a mass pre-event vaccination program,
      within reasonable boundaries, are known. The extent of contagion that could
      result from an aerosolized release of virus is unknown and may have been
      underestimated. Pre-event vaccination of first responders is urged, and voluntary
      vaccination programs should be offered to the public. Two defenses against a
      vaccine-resistant, engineered variola virus are proposed for consideration.
      Methisazone, an overlooked drug, is reported to be effective for prophylaxis
      only. The extent of reduction in the incidence of smallpox with use of this agent
      is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators
      (face masks) worn by uninfected members of the public may prevent transmission of
      the virus.

PMID- 15578370
TI  - Old world leishmaniasis: an emerging infection among deployed US military and
      civilian workers.
AB  - Many veterans of Operation Iraqi Freedom are now returning to the United States
      after potential exposure to leishmaniasis. In the past year, large numbers of
      leishmaniasis cases of a magnitude not encountered in the United States since
      World War II have challenged clinicians in both the military and the civilian
      sectors. Many Reserve and National Guard troops were deployed to Iraq and are now
      back in their communities. Hundreds of leishmaniasis cases, which were managed by
      a few practitioners initially, permitted further appreciation of the epidemiology
      and diagnostic and treatment options for Old World leishmaniasis. We describe the
      current situation, with on-the-ground experience, complimented by a literature
      review, and we provide a practical list of options for the clinician likely to
      encounter this parasitic infection in the coming months and years.

PMID- 15578371
TI  - Prevalence, associated factors, and prognostic determinants of AIDS-related
      toxoplasmic encephalitis in the era of advanced highly active antiretroviral
      therapy.
AB  - BACKGROUND: Characteristics, associated factors, and survival probability of
      toxoplasmic encephalitis (TE) in the era of advanced highly active antiretroviral
      therapy (HAART) have not been fully clarified. METHODS: Data for 205 individuals
      with acquired immunodeficiency syndrome (AIDS)-related TE were derived from the
      Italian Registry Investigative NeuroAIDS database, and the cases were studied
      longitudinally to evaluate prevalence, clinical characteristics, and survival.
      Moreover, the relationship between the occurrence of TE and exposure to
      antiretroviral therapy and to TE prophylaxis was evaluated. RESULTS: With an
      overall prevalence of 26%, TE represented the most frequent neurological disorder
      in the cohort. Female sex, severe immunodeficiency, and absence of primary TE
      prophylaxis significantly increased the risk of TE, and previous exposure to
      antiretroviral therapy reduced the probability of disease occurrence. Thirty-six
      percent of patients who had received antiretroviral therapy developed TE,
      although in most of these cases, the patient experienced failure of
      antiretroviral therapy. Of note, 66% of patients who had experienced
      antiretroviral therapy did not receive prophylaxis for TE at TE diagnosis. The 1
      year probability of that infection with human immunodeficiency virus (HIV) would
      progress or that death would occur after TE was 40% and 23%, respectively.
      Cognitive symptoms, low CD4(+) cell count, not receiving HAART after TE, and
      initiating HAART >2 months after TE diagnosis were all significantly associated
      with an increased probability of progression of HIV infection. Not receiving
      HAART after diagnosis negatively affected survival. CONCLUSIONS: TE remains a
      highly prevalent disorder of the central nervous system, even in the late HAART
      era, particularly among severely immunosuppressed patients and in absence of
      prophylaxis. Considering that persons with TE have a high probability of early
      death, prophylaxis should be maintained in immunosuppressed patients who
      experience failure of antiretroviral therapy, and HAART should be initiated as
      soon as possible after TE diagnosis.

PMID- 15578372
TI  - Early versus deferred antiretroviral multidrug therapy in infants infected with
      HIV type 1.
AB  - BACKGROUND: The clinical impact of early antiretroviral multidrug therapy on the
      risk of early-onset severe human immunodeficiency virus (HIV) disease has not
      been evaluated on a large scale. METHODS: We evaluated the risk of early-onset
      events associated with acquired immunodeficiency syndrome (AIDS), particularly
      the risk of encephalopathy, among infants in the French Perinatal Cohort,
      according to whether antiretroviral multidrug therapy was initiated before or
      after the age of 6 months. RESULTS: Of 83 HIV-infected infants born in 1996 (when
      HAART became available) or later, 40 received early treatment on or before the
      age of 6 months, and 43 received deferred multidrug therapy after the age of 6
      months. In the group that received early multidrug therapy, no child developed an
      opportunistic infection or an encephalopathy during the first 24 months of life.
      In the deferred multidrug therapy group, 6 infants presented with a total of 7
      AIDS-associated events (P=.01), 3 of which were encephalopathies (P=.08). The
      small number of events prevented the identification of clinical and biological
      markers that accurately predict progression of early-onset severe HIV disease.
      CONCLUSION: In this observational study, infants who received multidrug therapy
      before 6 months of age did not have the early-onset severe form of childhood HIV
      disease. Further studies are needed to find accurate early markers of disease
      progression in this age group.

PMID- 15578373
TI  - The case for earlier treatment of HIV infection.
AB  - Current US guidelines advise that antiretroviral therapy for asymptomatic HIV
      patients should definitely be started for those who have CD4(+) cell counts of
      >200 cells/ microL, but antiretroviral therapy is often not started at CD4(+)
      cell counts much above that level. Guidelines advocating later therapy for HIV
      infection have been based mainly on sparse and limited cross-sectional data and
      have been predicated on avoiding drug-related toxicity and viral drug resistance.
      However, emerging data about factors that contribute to survival and the
      availability of newer, less toxic drugs are eroding this position. Earlier
      initiation of antiretroviral therapy--namely, for patients with CD4(+) cell
      counts of >350 cells/ microL--may, in fact, be associated with lower mortality,
      better immune improvement, and less drug-related toxicity. These findings
      coincide with the introduction of antiretroviral drugs that have become more
      effective and less difficult to take. Earlier initiation of therapy may also
      reduce HIV transmission, an important public health consideration, and may be
      beneficial in terms of overall therapeutic cost-effectiveness. Given these
      accumulating data, we believe reconsideration of the "when-to-start" question is
      timely and justified.

PMID- 15578374
TI  - Antiretroviral therapy: the "when to start" debates.

PMID- 15578375
TI  - Determinants of immune reconstitution inflammatory syndrome in HIV type 1
      infected patients with tuberculosis after initiation of antiretroviral therapy.
AB  - Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37
      antiretroviral-naive patients who were treated subsequently for tuberculosis and
      human immunodeficiency virus (HIV) type 1 infection. IRIS was related to
      increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells
      after 1 month of antiretroviral therapy and to dissemination of tuberculosis.
      These results have implications for the diagnosis of IRIS and the understanding
      of its pathogenesis.

PMID- 15578376
TI  - Prevalence of antibody to Bordetella pertussis antigens in serum specimens
      obtained from 1793 adolescents and adults.
AB  - Serum specimens were obtained from all subjects in the adolescent and adult
      acellular pertussis (aP) vaccine efficacy trial before and after immunization to
      study the prevalence of IgG and IgA antibody and geometric mean titers to 4
      Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who
      received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG
      antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae
      types 2 and 3, respectively, that were greater than or equal to the limit of
      quantitation of the enzyme-linked immunosorbent assay used in the analysis. There
      was minimal variation in antibody prevalence with respect to geographic area,
      age, sex, or race.

PMID- 15578377
TI  - Nosocomial transmission of congenital tuberculosis in a neonatal intensive care
      unit.
AB  - Congenital tuberculosis is uncommon, and nosocomial transmission from a
      congenitally infected infant to another infant has not been reported in the
      English literature. We report an investigation of 2 infants with tuberculosis who
      were cared for in the same neonatal intensive care unit. Isolates from both
      infants were genetically indistinguishable. Transmission between the 2 infants
      was likely due to contaminated respiratory equipment.

PMID- 15578378
TI  - Spectrum of pulmonary toxicity associated with the use of interferon therapy for
      hepatitis C: case report and review of the literature.
AB  - Hepatitis C is one of the leading causes of liver disease in the United States,
      and current recommendations for its treatment include the use of interferon
      (IFN). Pulmonary side effects, although uncommon, have been reported in
      association with the use of IFN. We report a case of interstitial granulomatous
      pneumonitis that occurred after therapy with IFN and ribavirin, and we review the
      literature concerning this entity and other forms of IFN-associated pulmonary
      toxicity in patients with hepatitis C. The purpose of the present study is to
      increase awareness of the unusually wide spectrum of pulmonary toxicities
      associated with the use of IFN and ribavirin, with the anticipation that IFN will
      be used more frequently in the future for the treatment of hepatitis C.

PMID- 15578379
TI  - About the guidelines for outpatient parenteral antimicrobial therapy.

PMID- 15578381
TI  - Anemia and infection.

PMID- 15578383
TI  - Risk factors for asymptomatic bacteriuria in women with diabetes.

PMID- 15578385
TI  - Legionnaires disease and the updated IDSA guidelines for community-acquired
      pneumonia.

PMID- 15578387
TI  - Empirical antifungal therapy in febrile neutropenic patients: caution about
      composite end points and the perils of P values.

PMID- 15578389
TI  - Fatal pneumocystis pneumonia with good syndrome and pure red cell aplasia.

PMID- 15578390
TI  - The cover art of the 15 June 2004 issue.

PMID- 15578391
TI  - Gram staining by physicians: an invaluable practice still seen in East Asia.

PMID- 15578392
TI  - Emerging microbiological trends in Candiduria.

PMID- 15578393
TI  - Kikuchi-Fujimoto disease: hydroxychloroquine as a treatment.
AB  - We describe a case of recurrent Kikuchi's disease in a South Asian-American man
      that was treated successfully with chloroquine and on recurrence with
      hydroxychloroquine. Each treatment led to a very prompt response.

PMID- 15578394
TI  - Burden of infection in patients with end-stage renal disease requiring long-term
      dialysis.
AB  - BACKGROUND: This study examines the spectrum of infections in a selected
      population of patients requiring long-term dialysis, enlarging the focus beyond
      infections associated with the dialysis process. METHODS: Infection data were
      reviewed from complete archived inpatient and outpatient dialysis records of 433
      patients who were treated at a single hospital-based dialysis program and its
      dialysis satellites over a 9-year period, from 1 January 1992 to 31 December
      2000. RESULTS: The study period included 424,700 days of dialysis experience. A
      total of 2412 episodes of bacterial or fungal infections were treated in 433
      patients. The infection rate was 5.7 episodes per 1000 days of dialysis. Patients
      received 5111 courses of antibiotics over 42,627 days of treatment, which
      cumulatively accounted for 10% of the total days of the study. Infections
      associated with hemodialysis vascular access devices comprised 20.5% of the total
      episodes. Infections below the knee (19.3% of infection episodes), pneumonia
      (13%), and other skin and soft-tissue infections (9%) were also important types
      and sources of infection, accounting for >42% of the total episodes. Eighty-two
      percent of the infections (1971 episodes) were acquired in the community. Of
      these, 868 (44%) required hospitalization. An additional 441 episodes were
      nosocomial. The profile of bacteria isolated from patients with community
      acquired infections mirrored that of bacteria recovered from patients with
      nosocomial infections. CONCLUSION: Patients with end-stage renal disease have an
      enormous burden of infection. The majority of the infections are unrelated to
      dialysis. Frequent and long-term antibiotic use and cohorting of patients in the
      dialysis unit have altered the microbiological flora of such individuals, with
      clinical and epidemiological implications.

PMID- 15578395
TI  - Early prediction of hepatitis C virus (HCV) infection relapse in nonresponders to
      primary interferon therapy by means of HCV RNA whole-blood analysis.
AB  - BACKGROUND: Routine analysis of serum and/or plasma specimens for hepatitis C
      virus (HCV) RNA does not always correctly reflect the response to antiviral
      therapy. Analysis of whole-blood specimens for detection of viral RNA should
      provide more-accurate prognostic information. METHODS: Whole-blood, serum, and
      plasma specimens (268 sample sets) were obtained from 56 patients who did not
      respond to initial interferon (IFN)- alpha 2b monotherapy (5 MU every 2 days for
      3 months). Specimens were analyzed for HCV RNA by 4 different types of reverse
      transcriptase polymerase chain reaction (RT-PCR) (Cobas Amplicor HCV-2.0 [Roche],
      LightCycler real-time PCR [Roche], and 2 in-house RT-PCRs) to determine whether
      specimen type can predict the rate of virologic response to high-dose treatment
      with IFN (10 MU every 2 days) and ribavirin (1-1.2 g/day). RESULTS: Of the 56
      patients who provided specimens, serum and plasma obtained from 18 tested
      negative for HCV RNA at the end of treatment, indicating a complete virologic
      response. In contrast, analysis of whole-blood specimens obtained at the same
      time revealed the presence of viral RNA in 12 of these 18 patients. All 12
      subjects had relapse of HCV in serum and plasma: 11 relapsed a median of 4 weeks
      after the end of treatment, and 1 relapsed 20 weeks after the end of treatment.
      None of these 12 patients--all of whom consistently had whole-blood specimens
      that tested positive and plasma and serum specimens that tested negative for HCV
      RNA up to 20 weeks before the end of treatment--showed a sustained virologic
      response (P=.0002). CONCLUSIONS: Results of whole-blood tests for detection of
      HCV RNA were highly predictive of viral relapse (positive predictive value, 100%)
      and thus may be useful tools for monitoring and tailoring IFN/ribavirin therapy.
      Testing of only serum or plasma specimens underestimates the true circulating HCV
      load and leads to an overestimation of antiviral response rates.

PMID- 15578396
TI  - Prediction of relapse following treatment for hepatitis C: is whole blood more
      than the sum of its parts?

PMID- 15578397
TI  - Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis
      infection in a targeted tuberculin testing program.
AB  - BACKGROUND: To determine the rates of hepatotoxicity and treatment completion
      associated with intermittent rifampin and pyrazinamide (RZ) therapy for latent
      tuberculosis infection, we evaluated a cohort of patients from a targeted
      tuberculin testing site in Tennessee. METHODS: From 4 February 2000 through 9
      November 2001, a total of 423 patients with latent tuberculosis infection
      received directly observed preventive therapy (DOPT) with RZ given twice weekly
      for 2 months. Most of the patients were young, Hispanic males who had recently
      immigrated to the United States. RESULTS: During treatment, hepatotoxicity
      developed in 29 patients (6.9%; hereafter referred to as "case patients"), and
      peak alanine aminotransferase (ALT) levels that were >10 times the upper limit of
      normal were noted in 18 case patients. Of the case patients, 14 had asymptomatic
      hepatotoxicity, and 2 required hospitalization; none of the case patients died.
      Hepatotoxicity developed after the receipt of 12 doses in more than half of the
      case patients, and 4 case patients received all 16 doses. The risk of RZ
      associated hepatotoxicity was independently associated with older age (odds ratio
      [OR], 1.07 per year; P=.01). In total, 352 patients (83.2%) completed RZ therapy.
      The strongest predictors for noncompletion of RZ treatment were the development
      of a clinical symptom (OR, 9.73; P<.001) and older age (OR, 1.08 per year;
      P=.001). CONCLUSIONS: Despite the use of DOPT, intermittent dosing, and vigilant
      monitoring throughout therapy, RZ was associated with an unacceptable risk of
      hepatotoxicity.

PMID- 15578398
TI  - Treatment of latent tuberculosis infection: back to the beginning.

PMID- 15578399
TI  - A randomized, double-blind study to assess the optimal duration of doxycycline
      treatment for human brucellosis.
AB  - BACKGROUND: Human brucellosis is usually treated with a combination of
      tetracyclines and aminoglycosides. However, the optimal duration of therapy has
      not been clearly determined. METHODS: We conducted a prospective, double-blind,
      randomized, multicenter study comparing treatment with doxycycline (100 mg po
      b.i.d.) for 30 days (30-day group) with the same dosage of doxycycline for 45
      days (45-day group) in patients with brucellosis without endocarditis,
      spondylitis, or neurobrucellosis. All patients were treated with gentamicin (240
      mg im once daily) for the first 7 days. Therapeutic outcome was evaluated by
      measuring relapse rates and drug safety. RESULTS: Seventy-three patients were
      included in each group. During the first 45 days after treatment, the percentage
      of patients with relapse was significantly higher in the 30-day group than in the
      45-day group (12.3% vs. 1.37%; relative risk, 9.00; 95% confidence interval [CI],
      1.17-69.2; P=.017). Between day 45 after treatment and 12 months after treatment,
      no further significant differences were found in relapse rates between groups
      (9.38% in the 30-day group vs. 11.11% in the 45-day group; relative risk, 0.84;
      95% CI, 0.31-2.30; P=.78). Overall, relapses occurred in 15 (20.55%) of 73
      patients in the 30-day group and in 9 (12.33%) of 73 patients in the 45-day group
      (relative risk, 1.67; 95% CI, 0.78-3.56; P=.264). Compliance and adverse effects
      were comparable in the 2 groups. CONCLUSIONS: Doxycycline treatment for 45 days
      significantly decreased early relapse rates among adults with brucellosis without
      increasing adverse effects.

PMID- 15578400
TI  - Reaching stability in community-acquired pneumonia: the effects of the severity
      of disease, treatment, and the characteristics of patients.
AB  - BACKGROUND: The natural history of the resolution of infectious parameters in
      patients with community-acquired pneumonia (CAP) is not completely known. The aim
      of our study was to identify those factors related to host characteristics, the
      severity of pneumonia, and treatment that influence clinical stability. METHODS:
      In a prospective, multicenter, observational study, we observed 1424 patients
      with CAP who were admitted to 15 Spanish hospitals. The main outcome variable was
      the number of days needed to reach clinical stability (defined as a temperature
      of <or=37.2 degrees C, a heart rate of <or=100 beats/min, a respiratory rate of
      <or=24 breaths/min, systolic blood pressure of >or=90 mm Hg, and oxygen
      saturation >or=90% or arterial oxygen partial pressure of >or=60 mm Hg). RESULTS:
      The median time to stability was 4 days. A Cox proportional hazard model
      identified 6 independent variables recorded during the first 24 h after hospital
      admission related to the time needed to reach stability: dyspnea (hazard ratio
      [HR], 0.76), confusion (HR, 0.66), pleural effusion (HR, 0.67), multilobed CAP
      (HR, 0.72), high pneumonia severity index (HR, 0.73), and adherence to the
      Spanish guidelines for treatment of CAP (HR, 1.22). A second Cox model was
      performed that included complications and response to treatment. This model
      identified the following 10 independent variables: chronic bronchitis (HR, 0.81),
      dyspnea (HR, 0.79), confusion (HR, 0.61), multilobed CAP (HR, 0.84), initial
      severity of disease (HR, 0.73), treatment failure (HR, 0.31), cardiac
      complications (HR, 0.66), respiratory complications (HR, 0.77), empyema (HR,
      0.57), and admission to the intensive care unit (HR, 0.57). CONCLUSIONS: Some
      characteristics of CAP are useful at the time of hospital admission to identify
      patients who will need a longer hospital stay to reach clinical stability.
      Empirical treatment that follows guidelines is associated with earlier clinical
      stability. Complications and treatment failure delay clinical stability.

PMID- 15578401
TI  - Understanding the natural history of community-acquired pneumonia resolution:
      vital information for optimizing duration of therapy.

PMID- 15578402
TI  - Community-based surveillance in the united states of macrolide-resistant
      pediatric pharyngeal group A streptococci during 3 respiratory disease seasons.
AB  - BACKGROUND: In 2001, a total of 48% of pharyngeal group A streptococci (GAS) from
      Pittsburgh children were macrolide resistant. We assessed macrolide resistance,
      resistance genes, and emm types among GAS in the United States. METHODS: In
      prospective, multicenter, community-based surveillance of pharyngeal GAS
      recovered from children 3-18 years old during 3 respiratory seasons (the 2000
      2001 season, the 2001-2002 season, and the 2002-2003 season), GAS were tested for
      macrolide resistance and underwent emm gene sequencing. Macrolide-resistant GAS
      were tested for resistance to clindamycin, and resistance genes were determined.
      RESULTS: Erythromycin resistance was observed in 4.4% of isolates from the 2000
      2001 season, 4.3% from the 2001-2002 season, and 3.8% from the 2002-2003 season
      (P=.80). Clindamycin resistance was found in 1.04% of isolates; annual rates of
      clindamycin resistance were stable (P=.75). The predominant resistance genotype
      each year was mef A (65%-76.9%; overall, 70.3%). Resistant isolates included
      strains representing 8-11 different emm types each year. Heterogeneity of emm
      subtypes, resistance genes, and clindamycin resistance was evident among
      resistant isolates within some emm types. Geographic variability in resistance
      rates was present each year. CONCLUSIONS: The macrolide resistance rate among
      pharyngeal GAS was <5% and was stable over the 3 seasons. However, rates varied
      among sites each year. There was no evidence of spread of a specific resistant
      clone, increasing clindamycin resistance, or escalation in median erythromycin
      MICs.

PMID- 15578403
TI  - New pertussis vaccination strategies beyond infancy: recommendations by the
      global pertussis initiative.
AB  - BACKGROUND: The Global Pertussis Initiative, an expert scientific forum, was
      established to address the ongoing problems associated with pertussis disease
      worldwide. METHODS: The group analyzed pertussis disease trends, developed
      recommendations to improve disease control through expanded vaccination
      strategies, and proposed solutions to barriers to implementation and support of
      research activities. RESULTS: Bordetella pertussis infection is endemic and
      continues to be a serious problem among unvaccinated or incompletely vaccinated
      infants. In addition, the reported incidence of pertussis disease is increasing
      in adolescents and adults, who not only experience a considerable health burden
      themselves but also infect vulnerable infants. CONCLUSIONS: Current vaccination
      strategies need to be reinforced. Expanded vaccination should include adding
      booster doses to existing childhood schedules (preschool or adolescent) and
      booster doses for those specific adult subgroups that have the highest risk of
      transmitting B. pertussis infection to infants (i.e., new parents, other contacts
      of newborns, and health care workers). More epidemiological studies and studies
      of disease transmission and the cost-effectiveness of vaccination would be
      valuable, and surveillance, diagnostic improvements, and educational campaigns
      are needed for implementation. However, as a prelude to universal adult
      vaccination, immediate universal adolescent vaccination should be instituted in
      countries in which it is economically feasible.

PMID- 15578404
TI  - Chickenpox or smallpox: the use of the febrile prodrome as a distinguishing
      characteristic.
AB  - BACKGROUND: The ability to differentiate chickenpox from smallpox is important
      for early recognition of bioterrorism events and prevention of false alarms. The
      febrile prodrome is a clinical feature used to differentiate these conditions.
      However, the prevalence of prodromal manifestations in chickenpox has not been
      well established. METHODS: We evaluated prodrome characteristics of all
      chickenpox cases identified through an active varicella surveillance program over
      a 21-month period. The frequencies of various prodromal manifestations among
      vaccinated and unvaccinated case patients were assessed, and the impact of other
      demographic features on these manifestations was evaluated. Data were analyzed to
      determine what proportion met the smallpox febrile prodrome criteria as
      elaborated in the Centers for Disease Control and Prevention algorithm for
      evaluating patients suspected of having smallpox. Finally, we compared our data
      with historical data on smallpox prodromes. RESULTS: Data on prodrome
      characteristics were available for 932 chickenpox cases. Prodromal fever was
      present in 37% of unvaccinated chickenpox case patients and in 25% of vaccinated
      case patients. Among unvaccinated case patients, adults were 70% more likely than
      children to have fever in the prodrome period. We found that prodromes are less
      common and less severe in chickenpox than in smallpox. Nevertheless, 7%-17% of
      unvaccinated chickenpox case patients meet the smallpox febrile prodrome
      criteria. CONCLUSIONS: Febrile prodromes occur in a significant proportion of
      patients with chickenpox, particularly among unvaccinated case patients and
      adults. Therefore, the febrile prodrome alone is not a sufficient marker of
      smallpox risk. All major and minor smallpox criteria should be considered
      together in assessing the likelihood of smallpox.

PMID- 15578405
TI  - Use of simple laboratory features to distinguish the early stage of severe acute
      respiratory syndrome from dengue fever.
AB  - BACKGROUND: The diagnosis of severe acute respiratory syndrome (SARS) is
      difficult early in the illness, because its presentation resembles that of other
      nonspecific viral fevers, such as dengue. Dengue fever is endemic in many of the
      countries in which the large SARS outbreaks occurred in early 2003. Misdiagnosis
      may have serious public health consequences. We aimed to determine simple
      laboratory features to differentiate SARS from dengue. METHODS: We compared the
      laboratory features of 55 adult patients with SARS at presentation (who were all
      admitted before radiological changes had occurred) and 147 patients with dengue.
      Features independently predictive of dengue were modeled by multivariate logistic
      regression to create a diagnostic tool with 100% specificity for dengue. RESULTS:
      Multivariate analysis identified 3 laboratory features that together are highly
      predictive of a diagnosis of dengue and able to rule out the possibility of SARS:
      platelet count of <140 x 10(9) platelets/L, white blood cell count of <5x10(9)
      cells/L, and aspartate aminotransferase level of >34 IU/L. A combination of these
      parameters has a sensitivity of 75% and a specificity of 100%. CONCLUSIONS:
      Simple laboratory data may be helpful for the diagnosis of disease in adults
      admitted because of fever in areas in which dengue is endemic when the diagnosis
      of SARS needs to be excluded. Application of this information may help to
      optimize the use of isolation rooms for patients presenting with nonspecific
      fever.

PMID- 15578406
TI  - Determinants of influenza vaccination, 2003-2004: shortages, fallacies and
      disparities.
AB  - BACKGROUND: The influenza outbreak of 2003-2004 received substantial media
      attention, including widespread reports of a severe season and vaccine shortages.
      Understanding the determinants of vaccine receipt is important for guiding
      immunization policies. METHODS: From February through June 2004, we administered
      a structured telephone survey to Tennessee residents, using random-digit dialing
      methodology. RESULTS: Questionnaires were completed by 4028 persons, of whom 2077
      (52%) had received influenza vaccination during the previous outbreak season. Of
      these 2077 vaccine recipients, 63% received vaccine at a private medical clinic,
      14% at a workplace, 11% at a health department, and 7% at a pharmacy. Three
      fourths of respondents reported a risk factor for which the Centers for Disease
      Control and Prevention recommends vaccination; of those, 41% went unvaccinated,
      including 26% who had seen a medical provider for other reasons during the
      influenza season. More than 40% of persons aged >or=50, more than half of health
      care workers, and 70% of pregnant women were not immunized. Blacks, rural
      residents, and lower-income respondents were significantly less likely to be
      immunized than were comparison groups. Of respondents who were vaccinated, 6%
      reported difficulties obtaining vaccination (most commonly, they reported that
      vaccine was not readily available). One-fourth of unvaccinated persons had been
      offered vaccination but had declined it; of these, 35% thought it unnecessary and
      33% believed it would make them ill. Of those not vaccinated, 8% reported
      requesting vaccination but not receiving it, most commonly because it was
      unavailable. CONCLUSIONS: Many barriers contribute to disparities in rates of
      influenza vaccination, of which inadequate supply is only one component. Myths
      regarding influenza vaccination persist tenaciously. A multifaceted approach to
      increasing immunization rates is critical.

PMID- 15578407
TI  - Are antimicrobial-impregnated catheters effective? Replace the water and grab
      your washcloth, because we have a baby to wash.
AB  - Significant controversy surrounds the usefulness of central venous catheters
      (CVCs) impregnated with antimicrobial agents (A-CVCs) for the prevention of
      catheter-related bloodstream infections (CRBSIs). In a recent issue of Clinical
      Infectious Diseases, we reviewed 11 published trials of A-CVCs versus uncoated
      CVCs, and we concluded that there is a lack of solid evidence to support a
      benefit of A-CVCs in reducing the rate of CRBSIs. A response to our review was
      recently published in Clinical Infectious Diseases. In this response, our
      colleagues assert that there is a large body of evidence that demonstrates a
      powerful decrease in the risk of infection, and they conclude that we should not
      waste precious resources while we perform additional research to confirm what we
      have already found to be true. Although these authors agree with us on the
      significant shortcomings of the studies used to support the use of A-CVCs, they
      dismiss the need for additional trials to demonstrate that the use of A-CVCs does
      reduce infections. This dismissal, however, cannot be justified, because of the
      existence of an ongoing, federally supported, multicenter, prospective, placebo
      controlled trial, led by our colleagues, that compares the rate of CRBSIs among
      patients randomized to receive either an A-CVC or a "placebo" uncoated CVC. That
      our colleagues are leading a trial that assesses the efficacy of A-CVCs versus
      placebo uncoated CVCs supports our viewpoint that the truth regarding the
      protective role of A-CVCs has yet to be determined. Because of the significant
      cost, potential toxicity, and risk of increased antimicrobial resistance
      associated with the use of A-CVCs, and until the results of the important trial
      conducted by our colleagues convincingly demonstrate that A-CVCs reduce the rate
      of clinically significant events (not just catheter colonization), we recommend
      that the use of A-CVCs be limited to investigational settings.

PMID- 15578408
TI  - Surgical site infection in the elderly population.
AB  - Surgical site infections (SSIs) account for 11% of nosocomial infections among
      older patients. This report reviews the available data and presents medical and
      surgical perspectives on the epidemiology, outcomes, and prevention of SSI in the
      elderly population. The risk for SSI does not seem to increase after the age of
      65 years. Several risk factors for SSI are similar among elderly patients and
      younger patients, but financial factors and factors related to health services
      may differ between the groups. The clinical presentation of infection and the
      pathogens that cause infection are similar among elderly patients and younger
      patients. However, the mortality rate, the duration of hospitalization, and the
      costs associated with hospital care are greater for elderly patients with SSI
      than for younger patients with SSI. Several modalities for SSI prevention have
      been well studied in the general surgical population but have not been
      specifically evaluated in the elderly surgical population. Insights and opinions
      pertaining to modalities for SSI prevention in the elderly population and areas
      of import for future research are discussed.

PMID- 15578409
TI  - Screening for inhalational anthrax due to bioterrorism: evaluating proposed
      screening protocols.
AB  - Eleven known cases of bioterrorism-related inhalational anthrax (IA) were treated
      in the United States during 2001. We retrospectively compared 2 methods that have
      been proposed to screen for IA. The 2 screening protocols for IA were applied to
      the emergency department charts of patients who presented with possible signs or
      symptoms of IA at Inova Fairfax Hospital (Falls Church, Virginia) from 20 October
      2001 through 3 November 2001. The Mayer criteria would have screened 4 patients
      (0.4%; 95% CI, 0.1%-0.9%) and generated charges of 1900 dollars. If 29 patients
      (2.6%; 95% CI, 1.7%-3.7%) with >or=5 symptoms (but without fever and tachycardia)
      were screened, charges were 13,325 dollars. The Hupert criteria would have
      screened 273 patients (24%; 95% CI, 22%-27%) and generated charges of 126,025
      dollars. In this outbreak of bioterrorism-related IA, applying the Mayer criteria
      would have identified both patients with IA and would have generated fewer
      charges than applying the Hupert criteria.

PMID- 15578410
TI  - Single-slice computed tomography and anthropometric skinfold analysis for
      evaluation of facial lipoatrophy in HIV-infected patients.
AB  - We assessed the value of computed tomography (CT) and anthropometric skinfold
      analysis for evaluating subcutaneous facial fat in human immunodeficiency virus
      infected patients. Patients with facial lipoatrophy had smaller areas of facial
      adipose tissue, lower ratios of adipose tissue area to total tissue area of the
      face, and lower malar skinfold values, compared with patients without facial
      wasting. CT may be a useful technique to diagnose and monitor facial lipoatrophy.

PMID- 15578411
TI  - Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during
      potent antiretroviral therapy.
AB  - Rapidly progressive Kaposi sarcoma (KS) lesions with lymphadenopathy and tissue
      swelling occurred in a patient during antiretroviral treatment, despite an
      increased CD4(+) lymphocyte count and decreased HIV-1 level and KS-associated
      herpesvirus replication, suggesting immune reconstitution inflammatory syndrome.
      Inflammation resolved coincident with decreases in the CD4(+) lymphocyte count
      during paclitaxel treatment, whereas KS cleared only after prolonged
      antiretroviral therapy and chemotherapy.

PMID- 15578412
TI  - Phenotypic differences between commercial Lactobacillus rhamnosus GG and L.
      rhamnosus strains recovered from blood.
AB  - The isolation of clinical isolates that are indistinguishable, by molecular
      methods, from the probiotic strain of Lactobacillus rhamnosus GG has been
      reported. We compared the virulence potential of these clinical isolates with
      that of the probiotic strain. It was observed that all isolates differed
      significantly in 1 or more phenotypic properties.

PMID- 15578413
TI  - BK virus infection in hematopoietic stem cell transplant recipients: frequency,
      risk factors, and association with postengraftment hemorrhagic cystitis.
AB  - Blood samples from 132 consecutive hematopoietic stem cell transplant recipients
      were obtained and tested weekly for BK virus DNA by use of quantitative real-time
      PCR. Forty-four patients (33%) developed BK viremia at a median of 41 days
      (range, 9-91 days) after transplantation. Patients with hemorrhagic cystitis that
      occurred after platelet engraftment had higher levels of viremia than did
      patients without hemorrhagic cystitis (median, 9.7x10(3) vs. 0 copies/mL; P=.008)
      and patients with hemorrhagic cystitis that occurred before platelet engraftment
      (median, 9.7x10(3) vs. 0 copies/mL; P=.0006). BK viremia also was strongly
      associated with postengraftment hemorrhagic cystitis in a time-dependent analysis
      (P=.004).

PMID- 15578414
TI  - Hereditary spherocytosis mimicking beta -lactam-induced hemolytic anemia.

PMID- 15578415
TI  - Limits to the use of the procalcitonin level as a diagnostic marker.

PMID- 15578416
TI  - Apoptotic cell death in canine hair follicle.
AB  - Apoptotic cell death is an essential homeostatic mechanism involved in the
      control of cellular turnover in a variety of adult tissues. Cytoplasmic and
      nuclear condensation morphologically define this process whose biochemical
      hallmark is extensive DNA fragmentation into discrete oligonucleosomic units.
      Hair follicle growth and regression has been shown to be correlated with
      apoptosis in humans, mice, rats and guinea pigs. The present study was carried
      out to evaluate its implication in canine hair biology in order to define the
      spatio-temporal relationship between apoptosis and the hair cycle in dogs. As
      assessed by terminal deoxy-nucleotidyl transferase-mediated d-UTP nick-end
      labelling (TUNEL) and by basic histological and ultrastructural assays, apoptotic
      cells appeared both in the growing and in the regressing follicle epithelium
      showing the well characterized morphological features described in the previous
      relevant literature.

PMID- 15578417
TI  - Apoptosis resistance in pigmented villonodular synovitis.
AB  - OBJECTIVE: Pigmented villonodular synovitis (PVNS) is a proliferative lesion
      originating from synovial tissue with a locally aggressive behaviour. We analysed
      the pathogenetic role of apoptosis resistance for sustained cell proliferation in
      PVNS. METHODS: The expression of bcl-2, p53 and Ki-67 was examined in 80 cases of
      PVNS using immunohistochemistry. In 43 of these cases, DNA content and
      distribution of cell-cycle phases were investigated by flow cytometry.
      Additionally, 10 cases of PVNS were analysed by multi-parametric flow cytometry
      for expression of p53, caspase3, and bcl-2 and by TUNEL to detect DNA
      fragmentation. RESULTS: No apoptotic cell fractions were detected in any
      investigated cases. Expression of bcl-2 was found in 84% of cases (up to 6.5% of
      cells) and was significantly associated with DNA-fragmentation observed by TUNEL
      (p=0.037). Orthologous p53 expression was observed in 37% of cases. The level of
      p53 expression correlated with the proliferative activity and the expression of
      both caspase3 (p=0.017) and bcl-2 (p=0.0013). (No statistically significant
      correlations between expression of bcl-2, p53, caspase3, DNA fragmentation or
      proliferative index and age, sex of patients, disease recurrence, growth pattern
      or size of lesion were found). CONCLUSION: Apoptosis resistance is a critical
      event in the progression of PVNS and may contribute to the survival of the
      proliferating synovial cells in PVNS and to the permanent slow progression of
      these lesions.

PMID- 15578418
TI  - Effects of triple therapy with octreotide, galanin and serotonin on a human colon
      cancer cell line implanted in mice: comparison between different routes of
      administration.
AB  - A human colon cancer cell line was implanted subcutaneously in nude mice. After 7
      days, the animals were divided into four groups. The first group received an
      intraperitoneal (i.p.) continuous infusion by an osmotic pump, the second was
      given i.p. bolus injections, the third received continuous subcutaneous (s.c.)
      infusion by an osmotic pump and the fourth group was given bolus s.c. injections.
      Each group was divided into 2 subgroups. The first subgroup received triple
      treatment with octreotide, galanin, and serotonin, 40 microg/kg body weight/day
      of each. The second subgroup was given sterile saline solution. Treatment lasted
      for 14 days. The volume and wet weight of the tumours in all treated groups
      tended to decrease, but was statistically significant only in the group with
      continuous i.p. infusion. The number of viable cells tended to decrease in all
      the treated groups, but was not statistically significant. Proliferation index
      was significantly reduced in mice given triple therapy i.p. as bolus injection
      and as continuous infusion, as compared with their respective controls. The
      apoptotic index increased significantly in mice receiving triple therapy as
      continuous i.p. infusion as revealed by both the TUNEL method and by poly (ADP
      ribose) polymerase (PARP) expression. The number of tumour blood vessels was
      significantly reduced in the mice given triple therapy as continuous i.p.
      infusion, as compared with controls. There was no statistical difference between
      animals treated by different routes, regarding proliferation or apoptosis of the
      cancer cells, or the number or mean luminal area of tumour blood vessels. The
      present investigation showed that regardless of the route of administration,
      triple therapy with octreotide, galanin and serotonin generally reduced the
      volumes, weights, viable cells, vascularization and proliferation of the tumours,
      as well as inducing apoptosis. Continuous i.p. infusion appears, however, to be
      the most effective route of administration.

PMID- 15578419
TI  - The distribution of CD34-positive stromal cells and myofibroblasts in colorectal
      carcinoid tumors.
AB  - In order to understand the stromal reaction associated with colorectal neoplasms,
      we examined specimens from 26 patients including normal colorectal tissues
      (n=15), carcinoid tumors (n=12), well differentiated adenocarcinomas (n=10), and
      poorly differentiated adenocarcinomas (n=4), using an immunohistochemical method.
      Myofibroblasts and CD34-positive stromal cells were distributed in the mucosa and
      in the area between the submucosal and subserosal layers, respectively. However,
      the distribution of these cells markedly changed with the invasion of neoplasms.
      Namely, myofibroblasts were abundant in the invasive stroma of all colorectal
      neoplasms. CD34-positive stromal cells were completely absent from the invasive
      stroma of colorectal cancers. On the other hand, CD34-positive stromal cells were
      absent from four out of five carcinoid tumor cases with lesions measuring less
      than 2 mm in size, but were present in all seven cases of carcinoid tumors
      measuring more than 2 mm. Double-immunostaining identified stromal cells
      expressing both ASMA and CD34 in several carcinoid tumor cases. Finally, no CD34
      positive stromal cells were observed in the invasive stroma of colorectal
      cancers. However, the distribution of these cells in carcinoid tumors may depend
      on the lesion size. Namely, CD34-positive stromal cells existed between
      neoplastic nests in large-sized carcinoid tumors. Myofibroblasts in the stroma of
      colorectal neoplasms may originate from CD34-positive stromal cells.

PMID- 15578420
TI  - Renal clear-cell carcinoma: an ultrastructural study on the junctional complexes.
AB  - Junctional complexes such as tight junctions, adherens junctions, and desmosomes
      play crucial roles in the structure and function of epithelial cells. These
      junctions are involved in increasing cell-cell contact and as well serve as
      signaling centers regulating multiple functions in epithelial cells. Carcinoma
      cell lines cultured in the laboratory generally lack junctional complexes.
      However, studies directed towards understanding the distribution of junctional
      complexes in human cancer tissues are lacking. In this study, we analyzed by
      electron microscopy the distribution of junctional complexes in patients
      diagnosed with renal clear-cell carcinoma. We found that both tight junctions and
      adherens junctions were drastically reduced in patients with cancer compared to
      normal tissues. Desmosomes were not detected in normal proximal tubules while
      distinctly present in cancer tissues. These results suggest that analysis of
      junctional complexes in human tumors should provide valuable information that
      might have prognostic and diagnostic value.

PMID- 15578421
TI  - ICAM-1 expression on endothelium and systemic cytokine production in cutaneous
      neutrophilic leukocytoclastic vasculitis in NZBxNZWF1 mice.
AB  - The present study has examined relationship between cutaneous microvessel injury
      and adhesion molecule expression on the endothelium by cytokines in NZBxNZWF1
      (B/WF1) mice, a model for human systemic lupus erythematosus. In advanced ages
      associated with overt clinical manifestation, but not in early ages, neutrophils
      with a minor proportion of monocytes and lymphocytes mainly adhered to the
      endothelium of capillary and the venule with fragmentation (leukocytoclasis),
      leading to the vascular injury (leukocytoclastic vasculitis). This was confirmed
      by the leak of monstral blue from the blood vessel. At this stage LFA-1+
      leukocytes adhered to intensely expressed ICAM-1 on the endothelium, and this was
      paralleled with a significant rise in IL-1 alpha and TNF-alpha in the
      circulation. The present study suggests that IL-1 alpha and TNF-alpha may, at
      least in part, be responsible for the increased ICAM-1 expression on endothelium
      in cutaneous microvessels, resulting in the vascular injury characterized by
      neutrophilic leukocytoclasis in B/WF1 mice.

PMID- 15578422
TI  - Histological evaluation of scar tissue inflammatory response: the role of hGH in
      diabetic rats.
AB  - This paper describes a polymer site-specific delivery system containing human
      growth hormone in an in vivo model of scarring in the diabetic state. Copolymer
      discs with the hormone were introduced into incisions made in rats previously
      injected with streptozotocin in order to induce diabetes. Tissue specimens for
      evaluation were obtained at 3, 7 or 10 days after the procedure. Study groups
      were healthy rats and diabetic rats untreated or treated with/without the
      hormone. Histological sections were prepared for light microscopy examination of
      wound zones. Three and 7 days after surgery, polymer remains could be observed in
      the subcutaneous tissue. These remnants induced a moderate foreign body reaction.
      The number of macrophages detected was directly related to neovessel formation
      and metalloelastase expression. The CD4+/CD8+ ratio was low during the initial
      follow up stages (3 and 7 days) in untreated diabetic rats, yet an increased
      ratio corresponding to areas around the polymer remains was noted in the animals
      treated with copolymer loaded with the growth hormone. Copolymer is biodegradable
      in vivo and may be used as a vehicle for the slow release of active substances.
      The presence of the hormone at the site of skin injury induces cell proliferation
      and enhances the repair process.

PMID- 15578423
TI  - An immunohistochemical study of the expression of cell-cycle-regulated proteins
      p53, cyclin D1, RB, p27, Ki67 and MSH2 in gallbladder carcinoma and its precursor
      lesions.
AB  - Gallbladder carcinomas are rare but highly lethal neoplasms. We examined the
      expression of five cell-cycle-related molecules (p53, RB, cyclin D1, p27, Ki-67),
      and MSH2, in 46 carcinomas, 14 adenomas, 15 low-grade dysplasias, 9 intestinal
      metaplasias and 20 normal gallbladder epithelia. The expression of these
      molecules was altered in gallbladder carcinomas and adenomas. In gallbladder
      carcinomas we observed increased expression of p53, cyclin D1, Ki-67, and MSH2
      together with decreased expression of RB and p27 protein. Aberrant expression of
      cyclin D1 and reduced expression of RB were noted in adenomas, and expression of
      cyclin D1 was elevated in low-grade dysplasias. However, there was no change in
      the levels of these cell-cycle molecules in metaplasia. Expression of p53, p27,
      Ki-67, and MSH2 was correlated with clinical stage (P<0.05) and there was also a
      correlation between the expression of Ki-67 and MSH-2 and patient age (P<0.05).
      These results suggest that altered expression of cell-cycle molecules p53, cyclin
      D1, RB, p27, and of MSH-2 is involved in the progression of gallbladder
      carcinomas.

PMID- 15578424
TI  - The participation of myofibroblasts in the capsular formation of human
      conventional and chromophobe renal cell carcinomas.
AB  - The presence of myofibroblasts has been elucidated in neoplastic capsules of
      various organs. In the present article, we examine the presence of myofibroblasts
      in the capsule of renal cell carcinoma (RCC) and discuss the origin of the
      myofibroblasts. Nineteen renal tumors (conventional RCC, n=17; chromophobe RCC,
      n=2) with evident and totally surrounded fibrous capsule were selected. Abundant
      myofibroblasts were immunohistochemically observed in the capsule of the RCCs.
      These findings were confirmed by electron and immunoelectron microscopic studies
      of three conventional RCCs. Type III and I collagens were predominant in the
      outer and inner layers of the RCC capsule, respectively. The cytoplasm of the
      tubular epithelial cells in the tissue surrounding the neoplastic capsule stained
      positively for transforming growth factor (TGF)-beta 1. In situ hybridization
      detected type I collagen mRNA in myofibroblasts of the capsule. Myofibroblasts
      may participate in the capsular formation of conventional and chromophobe RCCs
      through the collagen production.

PMID- 15578425
TI  - Gastrointestinal phenotype of GAD67lacZ transgenic mice with early postnatal
      lethality.
AB  - It has been proposed that gamma-aminobutyric acid (GABA) in the gut may function
      as a neurotransmitter, hormone and/or paracrine agent. Our aim was to examine
      transgenic mice of the GAD67-lacZ line with impaired postnatal growth and early
      postnatal lethality for gastrointestinal abnormalities. The gastrointestinal
      tract was dissected and processed for histology, immunohistochemistry, electron
      microscopy, western blotting and measurement of GAD activity. Homozygous mice of
      both sexes displayed an intestinal phenotype characterized by a fragile and
      haemorrhagic intestinal wall, a reduced number of villi, epithelial lesions and
      the occasional appearance of pseudostratified epithelium. The number of GABA
      immunoreactive enteroendocrine cells and mucin-secreting goblet cells increased
      significantly relative to wild-type epithelium. The appearance of GABA
      immunopositive neuronal perikarya and the lack of GABA-immunoreactive varicose
      fibres were observed in the enteric plexuses of transgenic mice. Tissue
      homogenates of transgenic mice showed higher levels of expression of GAD67 and
      GAD65 as compared with wild-type mice. Our results suggest that the possible
      reason underlying the growth impairment and postnatal lethality observed in GAD67
      transgenic mice is a functional impairment of GABAergic enteric neurons and
      disintegration of intestinal epithelium.

PMID- 15578426
TI  - Prognostic significance of augmented metallothionein (MT) expression correlated
      with Ki-67 antigen expression in selected soft tissue sarcomas.
AB  - In soft tissue sarcomas, the most important prognostic criteria include extent of
      malignancy (G), size of the tumour and intensity of Ki-67 antigen expression. In
      recent times expression of metallothionein (MT) in cells of some malignant
      processes of epithelial origin was found to correlate with intensity of Ki-67
      antigen expression and to carry a possible prognostic significance. The present
      study aimed at a demonstration of prognostic value of MT expression and at
      comparing it with Ki-67 antigen expression and G grade in selected soft tissue
      sarcomas. Immunohistochemical studies were performed on paraffin sections in 54
      cases of malignant fibrous histiocytoma (MFH), 18 cases of liposarcoma and 20
      cases of synovial sarcoma. The extent of MT and Ki-67 antigen expression was
      evaluated and an attempt was made to correlate the results with each other and
      with grade of the tumour. Expression of MT was evident both in the cytoplasm and
      in cell nuclei of all studied sarcomas. The most pronounced MT expression was
      noted in MFH-type tumours. The extent of Ki-67 antigen expression was similar in
      MFH and liposarcoma and was the lowest in synovial sarcoma. In MFH, liposarcoma
      and synovial sarcoma a pronounced positive correlation was documented between
      expression of MT and Ki-67 antigen (r=0.85; p<0.001; r=0.93, p<0.0001; r=0.79,
      p<0.0001). In all types of the tumours a positive relation was detected between
      MT expression, expression of Ki-67 and G grade of malignancy in the tumour.
      Moreover, patients with higher MT expression in the studied tumours demonstrated
      a shorter survival. MT expression in soft tissue tumours of MFH, liposarcoma and
      synovial sarcoma type strongly correlated with intensity of proliferation (Ki-67)
      and G grade and could be useful in defining the extent of malignancy and in
      prognostic appraisal in the tumours.

PMID- 15578427
TI  - Alpha 1-acid glycoprotein (AGP): a possible carrier of sialyl lewis X (slewis X)
      antigen in colorectal carcinoma.
AB  - OBJECTIVES: 1- to detect alpha 1-acid glycoprotein (AGP) and sialyl Lewis x
      (sLex) in colorectal malignant, benign and normal samples; 2- to isolate AGP from
      colorectal cancer and 3- to study its immunoreactivity with an anti-sLex
      monoclonal antibody (MAb). MATERIALS AND METHODS: tissue and serum samples from
      88 patients with colorectal cancer, 22 adenomas and 23 normal were included.
      Expression of AGP and sLex was studied by immunohistochemistry (IHC); isolation
      approach: AGP was precipitated with ammonium sulphate and immunoprecipitated with
      anti-AGP MAb. The immune complex formed was isolated by protein A-Sepharose CL-4B
      affinity chromatography and further eluted; fractions were analysed by SDS-PAGE
      and Western-blot. Statistical analysis was performed by means of Principal
      Component Analysis. RESULTS: By Western blot employing anti-AGP MAb and sLex
      MAbs, isolated fractions from malignant samples showed a band at about 45 kD. IHC
      revealed that AGP was expressed in 70% of colorectal carcinoma samples, 50% of
      benign and 35% of normals. SLex was detected in 31% of malignant samples, 41% of
      benign and in one normal sample. In malignant samples, AGP reaction comprised the
      whole specimen with a strong and homogeneous staining while normal and benign
      samples showed a restricted reaction. In cancer, sLex expression consisted in an
      intense reactivity in membrane, cellular debris and some cytoplasmic foci while
      normal and benign samples were occasionally stained. A statistically significant
      positive correlation was found between AGP and sLex expression. Serum AGP levels
      were measured by radial immunodiffusion and statistical comparative analysis with
      tissue expression did not show a correlation between both parameters. CONCLUSION:
      AGP may constitute a carrier of sLex in colorectal cancer.

PMID- 15578428
TI  - Matrix metalloproteinase imbalance in muscle disuse atrophy.
AB  - Muscle atrophy commonly occurs as a consequence of prolonged muscle inactivity,
      as observed after cast immobilization, bed rest or space flights. The molecular
      mechanisms responsible for muscle atrophy are still unknown, but a role has been
      proposed for altered permeability of the sarcolemma and of the surrounding
      connective tissue. Matrix metallo-proteinases (MMPs) are a family of enzymes with
      proteolytic activity toward a number of extracellular matrix (ECM) components;
      they are inhibited by tissue inhibitors of MMPs (TIMPs). In a rat tail-suspension
      experimental model, we show that after fourteen days of non-weight bearing there
      is increased expression of MMP-2 in the atrophic soleus and gastrocnemius and
      decreased expression of TIMP-2. In the same experimental model the expression of
      Collagen I and Collagen IV, two main ECM components present in the muscles, was
      reduced and unevenly distributed in unloaded animals. The difference was more
      evident in the soleus than in the gastrocnemius muscle. This suggests that muscle
      disuse induces a proteolytic imbalance, which could be responsible for the
      breakdown of basal lamina structures such as Collagen I and Collagen IV, and that
      this leads to an altered permeability with consequent atrophy. In conclusion, an
      MMP-2/TIMP-2 imbalance could have a role in the mechanism underlying muscle
      disuse atrophy; more studies are needed to expand our molecular knowledge on this
      issue and to explore the possibility of targeting the proteolytic imbalance with
      MMP inhibitors.

PMID- 15578429
TI  - Changes in extranucleolar transcription during actinomycin D-induced apoptosis.
AB  - Actinomycin D (AMD) inhibits DNA-dependent RNA polymerases and its selectivity
      depends on the concentration used; at very high concentrations it may also induce
      apoptosis. This study investigates the effects of different concentrations (0.01
      to 1 microg/ml) of AMD on RNA transcription and maturation and on the
      organization of nuclear ribonucleoproteins (RNPs), and their relationship with
      apoptosis induction. Human HeLa cells were used as a model system. At the lowest
      concentration used, AMD induced the segregation of the nucleolar components and
      impaired r-RNA synthesis, as revealed by the decreased immunopositivity for bromo
      uridine incorporation and for DNA/RNA hybrid molecules. The synthesis of pre
      mRNAs, on the contrary, was active, while the immunolabeling of snRNP proteins
      and of the SC-35 splicing factor strongly decreased on perichromatin fibrils
      (where they are involved in co-transcriptional splicing). This suggests that the
      post-transcriptional maturation of extranucleolar RNAs was also affected.
      Moreover, still in the absence of typical late morphological or biochemical signs
      of apoptosis (i.e. chromatin condensation), these cells displayed the early
      apoptotic features, i.e. the externalization of phosphatidylserine residues on
      the plasma membrane and propidium iodide exclusion in vivo. At the highest
      concentrations of AMD used, apoptosis massively occurred, with the typical
      morphological events (progressive chromatin condensation, clustering of snRNPs
      and SC-35 splicing factor, cell blebbing). However, transcription of hnRNAs was
      maintained in the residual areas of diffuse chromatin up to advanced apoptotic
      stages. The inhibition of rRNA synthesis and the defective pre-mRNA maturation
      seem to be part of the apoptotic process induced by AMD.

PMID- 15578430
TI  - Expression of the ets-1 proto-oncogene in human breast carcinoma: differential
      expression with histological grading and growth pattern.
AB  - The proto-oncogene, ets-1, is a transcription factor known to control the
      expression of a number of genes and has been postulated to play a role in cell
      growth, differentiation and tumour invasion. We examined 137 cases of breast
      carcinoma by immunohistochemistry and compared the degree of Ets-1 expression
      among the different histological types of invasive carcinomas. Ets-1 was not
      expressed in the normal breast epithelium nor in noninvasive carcinomas. Among
      the 137 breast carcinoma cases, 104 (83.2%) showed positive staining for the Ets
      1 protein. Histologically, invasive ductal carcinomas expressed immunopositivity
      with intense staining for Ets-1 in the tumour cells. Ets-1 expression correlated
      with Bloom-Richardson grading in invasive ductal carcinoma (p<0.01). However,
      there was no correlation between Ets-1 expression and lymph node metastasis, "t"
      classification or TNM staging. In situ hybridization confirmed the presence of
      Ets-1 mRNA in breast carcinomas. The expression of Ets-1 mRNA was detected in two
      of three different kinds of cultured human breast carcinoma cell lines and one of
      three human breast carcinoma tissues by the reverse transcription polymerase
      chain reaction method. These findings suggest that ets-1 is overexpressed in
      ductal cells of the breast that have undergone malignant conversion and that ets
      1 is one of the factors associated with tumour growth and histological
      differentiation of breast carcinomas.

PMID- 15578431
TI  - The appearance of myofibroblasts and the disappearance of CD34-positive stromal
      cells in the area adjacent to xanthogranulomatous foci of chronic cholecystitis.
AB  - We investigated the distribution of myofibroblasts and CD34-positive stromal
      cells in normal gallbladder and its pathological conditions (cholecystitis, n=25)
      using immunohistochemistry and in situ hybridization. In the wall of normal
      gallbladder, myofibroblasts were generally absent from all layers, but many CD34
      positive stromal cells were observed in the connective tissue layer. In chronic
      cholecystitis with mild perimuscular fibrosis, a small to moderate number of
      myofibroblasts appeared in the mucosal layer. In chronic cholecystitis with
      marked perimuscular fibrosis, a small to large number of myofibroblasts appeared
      predominantly in the connective tissue layer, whereas the number of CD34-positive
      stromal cells decreased at the same location, although the number of
      myofibroblasts increased. In chronic cholecystitis with xanthogranulomatous foci,
      a small to large number of myofibroblasts were observed in the periphery of the
      xanthogranulomatous reaction and adjacent area. In contrast, CD34-positive
      stromal cells were completely absent or were limited to the area just around the
      xanthogranulomatous reaction. Induction of collagen type I and III mRNA was
      predominantly observed in the cytoplasm of myofibroblasts associated with the
      marked fibrosis, which consisted primarily of mature collagen fibers, and in the
      cytoplasm of myofibroblasts around the xanthogranulomatous reaction,
      respectively. Finally, myofibroblasts were observed in all subtypes. The
      increased number of myofibroblasts was most prominent in the connective tissue
      layer of chronic cholecystitis with marked perimuscular fibrosis or in the area
      adjacent to xanthogranulomatous foci of chronic cholecystitis. Under these
      conditions, CD34-positive stromal cells tended to disappear from the connective
      tissue layer, which exhibited an increase in myofibroblasts.

PMID- 15578432
TI  - Effect of the arterial hypertension and captopril treatment on the angiotensin II
      content in the subfornical organ. A study in SHR rats.
AB  - We studied the effects of spontaneous high blood pressure and the captopril
      treatment on the subfornical organ (SFO) of rats. The brains of control Wistar
      Kyoto rats (WKY), WKY rats treated with captopril (WKY-T), spontaneously
      hypertensive rats (SHR) and SHR rats treated with captopril (SHR-T) were
      processed immunohistochemically using anti-angiotensin II as primary antibody.
      Immunorective material (IRM) for angiotensin II was observed in a group of
      neurons and some cells of the ependymal layer of the SFO in WKY rats. The
      angiotensin II immunoreactive (AGII-ir) in the SHR rats was decreased, showing
      positive reaction only in a few neurons, while captopril treatment induced an
      increase in immunoreactive material in hypertensive rats, but contrarily, the
      expression of AGII-ir in the WKY-T group was scarce. The variations of the
      angiotensin II observed in the SFO could be owing to an interaction between the
      hypertension and its captopril treatment.

PMID- 15578433
TI  - Advances in isolation and characterization of homogeneous cell populations using
      laser microdissection.
AB  - The isolation and characterization of homogeneous cell populations are of great
      importance for the analysis of gene expression, because normal tissues contain
      various types of cells, and the differences in the populations of isolated cells
      exert significant effects on gene expression analysis. Researchers have attempted
      to develop methods for the isolation of homogeneous cell populations, such as
      flow cytometry and mechanical dissection. However, the recent emergence of laser
      assisted microdissection has revolutionized the isolation of single-cell
      populations from solid tissues. With the help of a cutting laser, laser
      microdissection can isolate tissues (cells) of interest without contamination
      from surrounding tissues with the microscopic visualization field. By combining
      laser microdissection and subsequent microarray technology, several studies have
      resulted in the identification of disease-related genes. In this review, we
      summarize the principle of laser microdissection and provide several successful
      examples of target-gene identification using the conventional method combining
      laser microdissection and microarray. Next, we discuss the practical drawbacks of
      the combinational method, such as the need for a large number of cells and the
      disturbance of the relative abundance of transcripts during RNA amplification. We
      introduce our modifications to combined laser microdissection and microarray for
      detection of disease-related genes; the technique is simple, yet practical and
      accurate. Finally, versatile applications of laser microdissection, not only to
      transcript expression analysis, but also to other genomics and proteomics
      analyses are, also presented.

PMID- 15578434
TI  - Molecular pathology of low malignant bladder transitional cell carcinoma: a
      current perspective.
AB  - Bladder transitional cell carcinoma (BTCC) actually has two phenotypes: low
      malignant and aggressive. Most previous molecular and cytogenetic analyses of
      bladder cancer were focused on aggressive BTCC. Little is known about the events
      that lead to the development of low malignant BTCC. This review mainly introduces
      the concept of two types of bladder tumors and then focuses on the molecular
      pathology of low malignant BTCC in particular. It is hoped that further
      understanding of the molecular pathology of low malignant BTCC may provide novel
      therapies and many other clinical benefits in patients with this disease.

PMID- 15578435
TI  - Characteristics of lymphatic endothelial cells in physiological and pathological
      conditions.
AB  - Impairment of lymphatic structure and function, e.g., inadequate endothelial
      permeability and intercellular openings, abnormal lymphangiogenesis and
      overexpression for immunoreactive agents, will result in tumor metastasis,
      autoimmune response alteration and accumulation of interstitial fluid and
      proteins. Recently, several novel molecules have been identified that allow a
      more precise distinction between lymphatic and blood vascular endothelium. The
      differences in expression of endothelial markers on the lymphatic vessel strongly
      suggest the possibility that there will be important divergence in the
      differentiating and regenerating responses in lymphatic behavior to various
      pathological processes. Undoubtfully, molecular techniques would also lead to the
      definition of unique markers found on lymphatic endothelial cells (LECs) in
      lymphatic-associated diseases which are mostly involved in lymphangiogenesis.
      This review is mainly concentrated on the characteristics of LECs in diabetes,
      wound healing, lymphedema and tumor, especially in the experimental models that
      have offered insight into the LEC role in these diseases affecting the lymphatic
      system. Increased knowledge of the molecular signaling pathways driving lymphatic
      development and lymphangiogenesis should boost the impact of therapeutics on the
      diseases. Although the field about the mechanisms that control the formation and
      lineage-specific differentiation and function of lymphatic vessels has
      experienced rapid progress in the past few years, an understanding of the basis
      of the differences and their implications in the pathological conditions will
      require much more investigation.

PMID- 15578436
TI  - Matrix metalloproteinase stromelysin-3 in development and pathogenesis.
AB  - The extracellular matrix (ECM) serves as a medium for cell-cell interactions and
      can directly signal cells through cell surface ECM receptors, such as integrins.
      In addition, many growth factors and signaling molecules are stored in the ECM.
      Thus, ECM remodeling and/or degradation plays a critical role in cell fate and
      behavior during many developmental and pathological processes. ECM
      remodeling/degradation is, to a large extent, mediated by matrix
      metalloproteinases (MMPs), a family of extracellular or membrane-bound, Zn2+
      dependent proteases that are capable of digesting various proteinaceous
      components of the ECM. Of particular interest among them is the MMP11 or
      stromelysin-3, which was first isolated as a breast cancer associated protease.
      Here, we review some evidence for the involvement of this MMP in development and
      diseases with a special emphasis on amphibian metamorphosis, a postembryonic,
      thyroid hormone-dependent process that transforms essentially every organ/tissue
      of the animal.

PMID- 15578437
TI  - Antigen receptor signaling competence and the determination of B cell fate in B
      lymphopoiesis.
AB  - Recent studies suggest that developmental check-points in B-lymphopoiesis are set
      in order to test the B cell receptor signaling competence. In these check-points
      ligand-independent and ligand-dependent receptor signals confer B-lymphopoiesis
      with positive and negative selection events. As a consequence, B-lymphocytes are
      forced to make crucial fate decisions to determine developmental progression,
      survival or apoptosis. In here we review recent progress in unraveling molecular
      and cellular mechanisms for the role of B cell receptor signaling competence in
      determination of the B cell fate.

PMID- 15578438
TI  - The role of junctional adhesion molecules in cell-cell interactions.
AB  - Cell-cell-interactions are important for the regulation of tissue integrity, the
      generation of barriers between different tissues and body compartments thereby
      providing an effective defence against toxic or pathogenic agents, as well as for
      the regulation of inflammatory cell recruitment. Intercellular interactions are
      regulated by adhesion receptors on adjacent cells which upon extracellular ligand
      binding mediate intracellular signals. In the vasculature, neighbouring
      endothelial cells interact with each other through various adhesion molecules
      leading to the generation of junctional complexes like tight junctions (TJs) and
      adherens junctions (AJs) which regulate both leukocyte endothelial interactions
      and paracellular permeability. In this context, emerging evidence points to the
      importance of the family of junctional adhesion molecules (JAMs), which are
      localized in tight junctions of endothelial and epithelial cells and are
      implicated in the regulation of both leukocyte extravasation as well as junction
      formation and permeability.

PMID- 15578439
TI  - Reactive oxygen species and the mitochondrial signaling pathway of cell death.
AB  - Reactive oxygen species (ROS) are produced as a by-product of cellular metabolic
      pathways and function as a critical second messenger in a variety of
      intracellular signaling pathways. Thus, a defect or deficiency in the anti
      oxidant defense system on the one hand and/or the excessive intracellular
      generation of ROS on the other renders a cell oxidatively stressed. As a
      consequence, direct or indirect involvement of ROS in numerous diseases has been
      documented. In most of these cases, the deleterious effect of ROS is a function
      of activation of intracellular cell-death circuitry. To that end, involvement of
      ROS at different phases of the apoptotic pathway, such as induction of
      mitochondrial permeability transition and release of mitochondrial death
      amplification factors, activation of intracellular caspases and DNA damage, has
      been clearly established. For instance, the ROS-induced alteration of
      constitutive mitochondrial proteins, such as the voltage-dependent anion channel
      (VDAC) and/or the adenine nucleotide translocase (ANT) can induce the pro
      apoptotic mitochondrial membrane permabilization. Not only do these observations
      provide insight into the intricate mechanisms underlying a variety of disease
      states, but they also present novel opportunities for the design and development
      of more effective therapeutic strategies.

PMID- 15578440
TI  - Review of mucinous tubular and spindle-cell carcinoma of the kidney with a focus
      on clinical and pathobiological aspects.
AB  - Recently, the characterization of mucinous tubular and spindle-cell carcinoma
      (MTSCC) has been established. MTSCC predominantly occurs in females. This tumor
      is histologically characterized by eosinophilic cytoplasm, elongated and
      anastomosing tubules, myxomatous stroma and low-grade nuclear cytology.
      Proliferation of spindle cells or foci of clear cells are also observed.
      Histochemically, the myxomatous stroma exhibits a positive reaction for alcian
      blue and colloidal iron stainings. Ultrastructurally, short microvilli are
      focally observed and junctional complexes are present. Recently, multiple losses
      of chromosomes 1, 4, 6, 8, 9, 13, 14, 15 and 22 in MTSCC have been elucidated by
      using comparative genomic hybridization. The prognosis of MTSCC is generally
      favorable, but some cases may show local recurrence or metastasis. Some cases
      with MTSCC seem to show overlapping histology with low-grade collecting-duct
      carcinoma. Therefore, further investigation will be needed to elucidate
      pathobiological characteristics of MTSCC.

PMID- 15578441
TI  - Gene expression analysis in sections and tissue microarrays of archival tissues
      by mRNA in situ hybridization.
AB  - Altered expression of genes in diseased tissues can prognosticate a distinct
      natural progression of the disease as well as predict sensitivity or resistance
      to particular therapies. Archival tissues from patients with a known medical
      history and treatments are an invaluable resource to validate the utility of
      candidate genes for prognosis and prediction of therapy outcomes. However, stored
      tissues with associated long-term follow-up information typically are formalin
      fixed, paraffin-embedded specimen and this can severely restrict the methods
      applicable for gene expression analysis. We report here on the utility of tissue
      microarrays (TMAs) that use valuable tissues sparingly and provide a platform for
      simultaneous analysis of gene expression in several hundred samples. In
      particular, we describe a stable method applicable to mRNA expression screening
      in such archival tissues. TMAs are constructed from sections of small drill
      cores, taken from tissue blocks of archival tissues and multiple samples can thus
      be arranged on a single microscope slide. We used mRNA in situ hybridization
      (ISH) on >500 full sections and >100 TMAs for >10 different cDNAs that yielded
      >10,000 data points. We provide detailed experimental protocols that can be
      implemented without major hurdles in a molecular pathology laboratory and discuss
      quantitative analysis and the advantages and limitations of ISH. We conclude that
      gene expression analysis in archival tissues by ISH is reliable and particularly
      useful when no protein detection methods are available for a candidate gene.

PMID- 15578442
TI  - Involvement of the phosphoinositide 3-kinase/Akt signaling pathway in the
      resistance to therapeutic treatments of human leukemias.
AB  - A major factor undermining successful cancer treatment is the occurrence of
      resistance to conventional treatments such as chemotherapy and ionizing
      radiation. Evidence accumulated over the recent years has indicated the
      phosphoinositide 3-kinase/Akt signal transduction pathway as one of the major
      factors implicated in cancer resistance to conventional therapies. Indeed, the
      phosphoinositide 3-kinase/Akt axis regulates the expression and/or function of
      many anti-apoptotic proteins which strongly contributes to cancer cell survival.
      As a result, small molecules designed to specifically target key components of
      this signaling network are now being developed for clinical use as single
      therapeutic agents and/or in combination with other forms of therapy to overcome
      resistance. Initially, the phosphoinositide 3-kinase/Akt signal transduction
      pathway has been mainly investigated in solid tumors. Recently, however, this
      network has also been recognized as an important therapeutic target in human
      leukemias. Specific inhibition of this signalling pathway may be a valid approach
      to treat these diseases and increase the efficacy of standard types of therapy.

PMID- 15578443
TI  - Emerging role of gap junctions in epilepsy.
AB  - This review highlights the contribution of gap junctions to the pathophysiology
      of epilepsy. The tissue expression and spatiotemporal regulation of connexins is
      discussed, and the phenotypes of specific connexin knockouts are considered.
      Electrophysiologic studies have implicated gap junctions in the generation of
      very fast oscillations preceding seizures. Gap junction inhibitors have shown
      powerful anticonvulsant effects, to date primarily in in vitro studies. Specific
      inhibition of gap junctions in vivo along with more detailed human tissue studies
      are needed to understand more fully the role of gap junctions in epileptogenesis.

PMID- 15578444
TI  - Exploring ischemia-induced vascular lesions and potential pharmacological
      intervention strategies.
AB  - Structural changes in vessels under the influence of ischemia play an important
      role in the pathogenesis of many diseases, most important of which are stroke and
      myocardial infarction or myocardial insult. Over the years, information has been
      gathered, which implicate a role for ischemic vascular changes in the
      pathogenesis of crush-syndrome, atherosclerosis and other vascular diseases. When
      blood vessels are damaged they become unresponsive to a stimulus, which normally
      elicits vasodilatation and can lead to intraluminal thrombosis and ischemic
      events. The aim of this review is to explore the structural changes seen in
      vessels affected by ischemia reperfusion injury. With ischemia, the development
      of observable changes to vascular structure is multifactorial. One key factor is
      reperfusion ischemic injury. Moreover, the duration of the ischemic event is an
      important factor when determining both the prognosis and the type of
      morphological change that is observable in affected vessel walls. In this regard,
      the deleterious progression of blood flow impairment and its severity depends on
      the specific organ involved and the type of tissue affected. Further, there are
      regional differences within affected tissues and the degree of microvascular
      injury is well correlated with differences in the nature and severity of the
      ischemic event. Any method aimed at preventing and treating ischemic reperfusion
      injuries in vessels, based on these investigations, should likewise be able to
      decrease the early signs of brain, cerebrovascular and heart injury and preserve
      normal cellular architecture.

PMID- 15578445
TI  - Akt signaling and its role in postnatal neovascularization.
AB  - Postnatal neovascularization has been known to be involved in not only
      angiogenesis but also vasculogenesis. Several lines of evidence suggest a link
      between neovascularization and Akt, a family member of serine/threonine protein
      kinases. Akt phosphorylates endothelial NO synthase (eNOS) and thereby enhances
      endothelial NO synthesis and influences postnatal vessel growth. Akt signaling is
      activated by a variety of stimuli in endothelial cells and endothelial progenitor
      cells (EPCs). Activation of the Akt kinase orchestrates a number of signaling
      pathways potentially involved in angiogenesis. Dominant negative Akt
      overexpression leads to functional blocking of EPC bioactivity. Because
      neovascularization is implicated in the pathophysiology of a number of diseases
      and is becoming an important therapeutic strategy for those diseases, further
      dissection of the Akt pathway and elucidation of the downstream effector
      molecules will lead to a better understanding of postnatal neovascularization and
      may provide avenues for the development of novel therapeutic interventions. In
      this review, molecular mechanisms of Akt signal pathway will be discussed with
      special emphasis on its role in neovascularization.

PMID- 15578446
TI  - Lymphangiogenesis and its role in cancer.
AB  - In many tumour types, lymphatic vasculature serves as a major route for tumour
      metastasis. The dissemination of malignant cells to the regional lymph nodes is
      an early step in the progression of many solid tumours and is an important
      determinant of prognosis. Lymphangiogenesis (formation of new lymphatic vessels)
      is thought to be crucial for cancer cells to metastasise to the regional lymph
      nodes. However research in this important process has been neglected largely due
      to the lack of molecular markers specific to the lymphatic endothelium. Recently,
      several specific markers have been identified including LYVE-1, podoplanin and
      prox-1. Although the biology of lymphangiogeneis, particularly its regulation, is
      still far from clear, it is now well established that tumours are lymphangiogenic
      i.e. they could induce the generation of their own lymphatics and metastasise to
      the regional lymph nodes. It is thought that the interruption of the main
      signalling pathways involved in this process could help to prevent lymphatic
      spread of many tumours. Furthermore, understanding the molecular mechanisms in
      lymphangiogenesis might help to develop new therapeutic strategies against cancer
      lymphatic spread. Here, we reviewed the literature in regards to the biology of
      lymphangiogenesis, its molecular regulation, lymphatic markers and the
      significance in human solid tumours.

PMID- 15578448
TI  - Diagnostic impact of bone marrow histopathology in polycythemia vera (PV).
AB  - The criteria of the Polycythemia Vera Study Group (PVSG), although acknowledged
      as the gold standard to establish the diagnosis of polycythemia vera (PV), do not
      regard bone marrow (BM) histopathology. Arguments include the existence of
      sufficient objective markers of disease and the lack of independently performed
      morphological studies or standardized criteria. The aim of this review is to
      evaluate morphological characteristics of erythrocytosis and to determine whether
      distinctive patterns of histopathology exist. A review of the pertinent
      literature and evaluation of 334 patients from our files with a borderline to
      marked increase in hemoglobin was performed. In extension to former descriptions
      of BM features by the PVSG, a tri-lineage myeloproliferation (panmyelosis) with a
      pleomorphous appearance of megakaryopoiesis revealed that, besides increase in
      size, there was a lack of gross cytological anomalies. Differentiation from
      secondary polycythemia (SP) was accomplished by regarding these features and the
      conspicuously expressed stromal changes (plasmacytosis, eosinophils, cell debris
      and iron deposits). In about 96% of this cohort a clear-cut separation from SP
      was achieved, even in the initial (latent) stages. When accompanied by an
      elevated platelet count, these precursor stages may clinically mimick essential
      thrombocythemia because they are not recognized by the conventional criteria.
      Advanced stages (spent phases) of PV were consistent with an increased left
      shifted granulocytic proliferation, accompanied by reduction of erythroid
      precursors and progressive myelofibrosis (post-polycythemic myeloid metaplasia).
      Finally, an increase in dysplastic changes and immaturity signalled a transition
      into blastic crisis. In conclusion, PV is characterized by a distinctive pattern
      of histopathology that has been gained in an independent and blind fashion and
      therefore, dissolves arguments about failing specificity.

PMID- 15578449
TI  - New aspects of the pathogenesis of osteoarthritis: the role of fibroblast-like
      chondrocytes in late stages of the disease.
AB  - It is thought that the general increase in life expectancy will make
      osteoarthritis the fourth leading cause of disability by the year 2020. Even
      though the pathogenesis of idiopathic osteoarthritis has not been fully
      elucidated, the main features of the disease process are the altered interactions
      between the chondrocytes and their surrounding extracellular matrix. In the
      course of these disturbances, three types of chondrocytes are typically present
      in the pathologically altered extracellular matrix of the articular cartilage:
      healthy chondrocytes which are continually undergoing degeneration, degenerated
      cells which are continually being degraded and finally fibroblast-like
      chondrocytes which seem not to be influenced by this process and, therefore, are
      found in ever-increasing numbers. These fibroblast-like chondrocytes take part in
      tissue regeneration even in advanced stages of osteoarthritis, but only in as
      much as they form fibrocartilaginous or scar tissue, since, as we were able to
      show, they mainly synthesize collagen type I and not collagen type II, typical
      for healthy cartilage. However, we were further able to show that fibroblast-like
      chondrocytes also produce increasing amounts of the proteoglycans decorin and
      biglycan which physiologically are involved in the formation of collagen type II,
      as well as perlecan. These multifunctional fibroblast-like chondrocytes could
      present an ideal therapeutic starting point if they could be modified to
      synthesize the collagen type II typical for cartilage and to, thereby, contribute
      to reversing the damage of the joint cartilage that has occurred by the late
      stages of osteoarthritis.

PMID- 15578447
TI  - Activating Akt and the brain's resources to drive cellular survival and prevent
      inflammatory injury.
AB  - Protein kinase B, also known as Akt, is a serine/threonine kinase and plays a
      critical role in the modulation of cell development, growth, and survival.
      Interestingly, Akt is ubiquitously expressed throughout the body, but its
      expression in the nervous system is substantially up-regulated during cellular
      stress, suggesting a more expansive role for Akt in the nervous system that may
      involve cellular protection. In this regard, a body of recent work has identified
      a robust capacity for Akt and its downstream substrates to foster both neuronal
      and vascular survival during apoptotic injury. Cell survival by Akt is driven by
      the modulation of both intrinsic cellular pathways that oversee genomic DNA
      integrity and extrinsic mechanisms that control inflammatory microglial
      activation. A series of distinct pathways are regulated by Akt that include the
      Forkhead family of transcription factors, GSK-3 beta, beta-catenin, c-Jun, CREB,
      Bad, IKK, and p53. Culminating below these substrates of Akt are the control of
      caspase mediated pathways that promote genomic integrity as well as prevent
      inflammatory cell demise. With further levels of progress in defining the
      cellular role of Akt, the attractiveness of Akt as a vital and broad
      cytoprotectant for both neuronal and vascular cell populations should continue to
      escalate.

PMID- 15578450
TI  - Evaluation of the efficacy and duration of immunity of a canine combination
      vaccine against virulent parvovirus, infectious canine hepatitis virus, and
      distemper virus experimental challenges.
AB  - The results of this study confirmed that dogs vaccinated subcutaneously with a
      commercially available multivalent vaccine containing modified-live canine
      distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine
      parainfluenza virus antigens were protected against sequential experimental
      challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age.
      All 10 vaccinates were protected against clinical diseases and mortality
      following parvovirus and infectious canine hepatitis experimental infections. All
      vaccinates were protected against mortality and 90% against clinical disease
      following distemper challenge. These data support at least a 4-year duration of
      immunity for these three "core" fractions in the combination vaccine.

PMID- 15578451
TI  - Evaluation of the efficacy of a commercial diet in the dissolution of feline
      struvite bladder uroliths.
AB  - Clinical signs of struvite urolithiasis resolved in an average of 19 days in cats
      fed either a canned or dry urine-acidifying, magnesium-restricted diet, and
      stones completely dissolved in 31 of 39 cats in an average of 30 days. Stones
      were surgically removed from five cats, and analysis revealed that these stones
      were not composed of struvite. The results of this study strongly suggest that
      the diet will dissolve naturally occurring feline struvite bladder uroliths.

PMID- 15578452
TI  - Evaluation of transdermal morphine and fentanyl pluronic lecithin organogel
      administration in dogs.
AB  - Transdermal administration of morphine and fentanyl using a pluronic lecithin
      organogel was evaluated in dogs. IV administration of morphine and fentanyl
      resulted in therapeutic serum drug concentrations. Following transdermal
      administration, however, median serum drug concentrations were never above the
      limit of quantitation for morphine or fentanyl. These findings indicate that use
      ofa pluronic lecithin organogel for transdermal administration of morphine or
      fentanyl cannot be justified.

PMID- 15578453
TI  - Use of imidacloprid-permethrin to prevent transmission of Anaplasma
      phagocytophilum from naturally infected Ixodes scapularis ticks to dogs.
AB  - One group of eight beagles was treated with a combination of imidacloprid and
      permethrin 7 days before exposure to Ixodes scapularis ticks that were naturally
      infected with Anaplasma phagocytophilum. A second group of eight beagles was not
      treated and was also exposed to infected ticks. Seven of eight non-treated dogs-
      but none of the treated dogs--developed specific antibodies to A.
      phagocytophilum. Results of this study indicate that a combination of
      imidacloprid and permethrin can prevent transmission of A. phagocytophilum to
      dogs if administered before exposure to infected ticks.

PMID- 15578454
TI  - Nutrient intake and urine composition in calcium oxalate stone-forming dogs:
      comparison with healthy dogs and impact of dietary modification.
AB  - Nutrient intake and urine composition were analyzed in calcium oxalate
      (CaOx)stone-forming and healthy control dogs to identify factors that contribute
      to CaOx urolithiasis. Stone-forming dogs had significantly lower intake of
      sodium, calcium, potassium, and phosphorus and significantly higher urinary
      calcium and oxalate concentrations, calcium excretion, and CaOx relative
      supersaturation (RSS). Feeding a diet used in the treatment of canine lower
      urinary tract disease for 1 month was associated with increased intake of
      moisture, sodium, and fat; reduced intake of potassium and calcium; and decreased
      urinary calcium and oxalate concentrations, calcium excretion, and CaOx RSS. No
      clinical signs of disease recurrence were observed in the stone-forming dogs when
      the diet was fed for an additional 11 months. The results suggest that
      hypercalciuria and hyperoxaluria contribute to the formation of CaOx uroliths in
      dogs and show that dietary modifications can alter this process.

PMID- 15578462
TI  - Emboli and renal dysfunction in CABG patients.

PMID- 15578463
TI  - Transcranial Doppler emboli count predicts rise in creatinine after coronary
      artery bypass graft surgery.
AB  - OBJECTIVE: To examine the correlation between transcranial Doppler
      ultrasonography-detected emboli during coronary artery bypass graft surgery with
      cardiopulmonary bypass and renal dysfunction as determined by the postoperative
      change in creatinine. DESIGN: Retrospective review of data from the anesthesia
      and cardiothoracic surgery databases. SETTING: Tertiary care university hospital.
      PARTICIPANTS: Two hundred eighty-six patients undergoing coronary artery bypass
      graft surgery. INTERVENTIONS: Transcranial Doppler ultrasonography of the right
      middle cerebral artery was performed after induction of general anesthesia
      through completion of the operation. Doppler signals were recorded and emboli
      counts determined using an automated counting system. MEASUREMENTS AND MAIN
      RESULTS: Renal dysfunction was assessed as the change in creatinine from the
      preoperative value to the maximum postoperative value (Delta-Cr). There was a
      significant (p = 0.0003) univariate correlation between postoperative change in
      creatinine and total number of Doppler-detected emboli. The effect of total
      number of emboli remained significant (p = 0.0038) in the multivariable analysis
      after adjustment for covariables (age, sex, number of grafts, left ventricular
      ejection fraction, hypertension, history of congestive heart failure, diabetes,
      cardiopulmonary bypass time, preoperative creatinine, and maximum postoperative
      creatinine). CONCLUSIONS: Increased numbers of Doppler-detected emboli during
      coronary artery bypass graft surgery are associated with postoperative renal
      dysfunction.

PMID- 15578464
TI  - Cerebral oxygen desaturation is associated with early postoperative
      neuropsychological dysfunction in patients undergoing cardiac surgery.
AB  - OBJECTIVE: To evaluate the relationship between cerebral oxygen saturation and
      neuropsychological dysfunction after cardiac surgery. DESIGN: Prospective and
      observational study. SETTING: Operating room and cardiac floor of a university
      hospital. PARTICIPANTS: One hundred one patients undergoing elective cardiac
      surgery with cardiopulmonary bypass INTERVENTION: Bilateral noninvasive cerebral
      oxygen saturations were monitored over the forehead. The anesthetic and surgical
      techniques were performed as usual, and no interventions were attempted based on
      the monitor. Neuropsychological outcome was assessed by the Mini-Mental State
      Examination (MMSE) and the antisaccadic eye movement test (ASEM). MEASUREMENTS
      AND MAIN RESULTS: Preoperative baseline values of cerebral oxygen saturation
      (rSO(2)) were 58.6% +/- 10.2%. Patients with the nadir rSO(2) <35% had
      significantly higher incidences of postoperative ASEM and MMSE impairments than
      those with rSO(2) always above 35% (44% and 33% v 12% and 9%, respectively).
      Patients with areas of rSO(2) <40% for more than 10 minutes . % presented with a
      significantly higher incidence of postoperative ASEM and MMSE impairments than
      those with areas of rSO(2) <40% for less than 10 minutes . % (42% and 32% v 13%
      and 10%, respectively). Patients with postoperative ASEM or MMSE impairment had
      significantly lower nadir rSO(2) and significantly larger areas of rSO(2) <40%,
      <45%, and <50% than those with normal postoperative neuropsychological outcome.
      However, multivariate logistic regression analysis showed that areas of rSO(2)
      <40% were the only predictor for both postoperative ASEM and MMSE impairments.
      CONCLUSIONS: Intraoperative cerebral oxygen desaturation is associated with early
      postoperative neuropsychological dysfunction in patients undergoing cardiac
      surgery with cardiopulmonary bypass. However, it remains to be determined whether
      interventions to maintain adequate cerebral oxygenation may improve
      neuropsychological outcome.

PMID- 15578465
TI  - Midlatency auditory-evoked potentials in the assessment of sedation in cardiac
      surgery patients.
AB  - OBJECTIVES: Midlatency auditory-evoked potentials (MLAEPs) may provide an
      objective measure of depth of sedation. The aim of this study was to evaluate
      MLAEPs for measuring sedation in cardiac surgery patients. DESIGN: Prospective
      study. SETTING: Intensive care unit of a university hospital. PARTICIPANTS:
      Twenty-two patients scheduled for elective coronary artery bypass grafting.
      INTERVENTIONS: MLAEPs were obtained at 5 time points: the day before surgery
      (baseline), 1 hour before surgery, after premedication, postoperatively during
      deep (Ramsay 6) and moderate (Ramsay 4) sedation, and the day after surgery.
      MEASUREMENTS AND MAIN RESULTS: The latency of the Nb MLAEP component increased
      from 44 ms (38-60 ms; median, range) at baseline to 49 ms (41-64 ms) after
      premedication (p = 0.03) and further to 63 ms (48-80 ms) during deep sedation
      after surgery (P < 0.01). Although a decreasing clinical level of sedation after
      rewarming was not associated with a significant change in Nb latency (61 ms [42
      78 ms]), the MLAEP NaPa amplitude increased from 0.9 muV (0.4-1.6 microV) to 1.3
      muV (0.8-3.9 microV; p = 0.01). Nb latency remained increased the day after
      surgery (49 ms [37-71 ms]) as compared with baseline (p < 0.01). CONCLUSIONS:
      MLAEP latencies can reflect subtle changes in auditory perception, while
      amplitudes seem to change with transition between deep levels of sedation.

PMID- 15578466
TI  - Measurement of cardiac output before and after cardiopulmonary bypass: Comparison
      among aortic transit-time ultrasound, thermodilution, and noninvasive partial CO2
      rebreathing.
AB  - OBJECTIVES: A noninvasive continuous cardiac output system (NICO) has been
      developed recently. NICO uses a ratio of the change in the end-tidal carbon
      dioxide partial pressure and carbon dioxide elimination in response to a brief
      period of partial rebreathing to measure CO. The aim of this study was to compare
      the agreement among NICO, bolus (TDCO), and continuous thermodilution (CCO), with
      transit-time flowmetry of the ascending aorta using an ultrasonic flow probe
      (UFP) before and after cardiopulmonary bypass (CPB). DESIGN: Prospective,
      observational human study. SETTING: Veterans Affairs Medical Center Hospital.
      PARTICIPANTS: Sixty-eight patients. METHODS: Matched sets of CO measurements
      between NICO, TDCO, CCO, and UFP were collected in 68 patients undergoing
      elective CABG at specific time periods before and after separation from CPB.
      After anesthetic induction, all patients had an NICO sensor attached between the
      endotracheal tube and the breathing circuit, a PAC floated into the pulmonary
      artery for TDCO and CCO monitoring, and a UFP positioned on the ascending aorta
      and used for the reference CO. Bland-Altman analysis was used to compare the
      agreement among the different methods. MEASUREMENTS AND MAIN RESULTS: Bland
      Altman analysis of CO measurements before CPB yielded a bias, precision, and
      percent error of 0.04 L/min +/- 1.07 L/min (44.8%) for NICO, 0.18 L/min +/- 1.01
      L/min (41.7%) for TDCO, and 0.29 L/min +/- 1.40 L/min (57.5%) for CCO compared
      with simultaneous UFP CO measurements, respectively. After separation from CPB
      (average 29 mins), bias, precision, and percent error were -0.46 L/min +/- 1.06
      L/min (37.3%) for NICO, 0.35 L/min +/- 1.39 L/min (46.1%) for TDCO, and 0.36
      L/min +/- 1.96 L/min (64.7%) for CCO compared with UFP CO measurements,
      respectively. CONCLUSIONS: Before initiation of CPB, the accuracy for all 3
      techniques was similar. After separation from CPB, the tendency was for NICO to
      underestimate CO and for TDCO and CCO to overestimate it. NICO offers an
      alternative to invasive CO measurement.

PMID- 15578467
TI  - Arterial versus venous sampling for activated coagulation time measurements
      during cardiac surgery: a comparative study.
AB  - OBJECTIVE: Activated coagulation times (ACTs) are widely used for monitoring
      anticoagulation during cardiac surgery. Significant variability of this test is
      well known. Variability in test results was studied, which may arise from the
      sample drawing site. DESIGN: Prospective study. SETTING: University hospital.
      PARTICIPANTS: Sixty-five patients scheduled for surgery requiring cardiopulmonary
      bypass were enrolled in the study. INTERVENTION: ACTs were assessed using the
      Hemochron 801 ACT machine. Samples were collected (1) baseline I from the
      arterial catheter before anesthetic induction, (2) baseline II from the arterial
      and venous collection sites after pulmonary artery catheterization, (3) after
      heparin administration, (4) 10 minutes after blood collection number 3, and (5)
      after protamine administration. MEASUREMENTS AND MAIN RESULTS: At the baseline
      II, the ACT measures using venous blood were significantly higher than that
      obtained using an arterial sample (p = 0.001). There was no significant
      difference in ACT measures obtained using either arterial or venous blood samples
      at the other time points. After heparin administration, the ACT variability in
      individual patients was quite striking, with ranges of up to 600 seconds in
      repeated measures. CONCLUSION: During the period of systemic anticoagulation,
      there is great individual variability between ACT measures obtained from venous
      and arterial samples. Further studies are required to analyze the cause of
      differences at the baseline and the source of variable coagulation times after
      heparin.

PMID- 15578468
TI  - Dose-response relationship between plasma ionized calcium concentration and
      thrombelastography.
AB  - OBJECTIVES: To establish the threshold value for calcium at which coagulation
      commenced and to investigate the range over which changes in ionized calcium
      influenced coagulation. DESIGN: Controlled, nonblinded, in vitro observational
      study. SETTING: The study was conducted in a university-based laboratory.
      PARTICIPANTS: Blood was obtained from healthy volunteers. INTERVENTIONS: One
      hundred samples of citrated blood were recalcified using varying quantities of
      10% calcium chloride solution. Heparinized samples from the recalcified blood
      were obtained for measurement of ionized calcium concentration (Ca(2+)).
      MEASUREMENTS AND RESULTS: Coagulation of the recalcified samples was analyzed
      using thrombelastography. The ionized calcium concentration in recalcified blood
      was measured using a calcium electrode in a blood gas analyzer. No sample with a
      Ca(2+) < 0.33 mmol/L showed any clot formation. Normal coagulation measures were
      obtained in almost all samples in which the Ca(2+) was >0.56 mmol/L. Final clot
      strength appeared to be independent of Ca(2+) once the threshold value of 0.33
      mmol/L was exceeded. CONCLUSIONS: Ca(2+) of <0.33 mmol/L is necessary to prevent
      coagulation. Ca(2+) > 0.56 is unlikely to be the cause of coagulation
      abnormalities during surgical procedures in which calcium metabolism is deranged.
      Between these values, Ca(2+) may exert an effect on the rate of clot formation,
      but final clot strength should be unaffected.

PMID- 15578469
TI  - Accuracy and performance of a modified continuous intravascular blood gas
      monitoring device during thoracoscopic surgery.
AB  - OBJECTIVE: The only commercially available continuous intravascular blood gas
      monitoring system for adults, the Paratrend (Diametrics Medical Inc, High
      Wycombe, UK), was modified by the manufacturer to the Paratrend 7+ (PT7+) in
      1999. The aim of this study was to evaluate the modified probe over a wide range
      of blood gas and pH values during thoracoscopic surgery in a similar setup as
      done with the previous model. DESIGN: Prospective methods comparison study.
      SETTING: University hospital. PARTICIPANTS: Twenty-three patients. INTERVENTIONS:
      Elective thoracoscopic surgery. MEASUREMENTS AND MAIN RESULTS: One hundred
      thirteen PT7+ readings and their corresponding arterial blood gas and pH
      measurements (ABGA) were evaluated. The ranges for ABGA values were 50 to 474
      mmHg for PO(2), 29 to 58 mmHg for PCO(2), and 7.28 to 7.49 for pH. Bland and
      Altman analysis revealed a bias +/- 2 standard deviation of -20 +/- 86 mmHg for
      PO(2), 3 +/- 9 mmHg for PCO(2), and -0.01 +/- 0.06 for pH. No specific
      complications attributable to the probe were observed. CONCLUSION: In patients
      undergoing thoracoscopic surgery with rapidly changing blood gas parameters, the
      PT7+ device is a valuable trend indicator and hence may be helpful for clinical
      decision making. However, the underestimation of PO(2) values by 20 mmHg on
      average and the wide limits of agreement documented in this study must be
      regarded as limiting factors.

PMID- 15578470
TI  - The effects of propofol on lipid peroxidation and inflammatory response in
      elective coronary artery bypass grafting.
AB  - OBJECTIVE: To determine whether the antioxidant and anti-inflammatory properties
      of propofol confer benefit in adult patients undergoing elective coronary artery
      bypass grafting. DESIGN: Prospective, blinded, randomized, controlled clinical
      investigation. SETTING: Single-center, university teaching hospital and academic
      research laboratory. PARTICIPANTS: Twenty-one adult patients (11 control, 10
      intervention) with chronic stable angina and normal ventricular function
      scheduled to undergo elective coronary artery bypass grafting. INTERVENTIONS: All
      patients received a standardized fentanyl-isoflurane anesthetic. Fifteen minutes
      before reperfusion, patients in the intervention group received a target
      controlled infusion of propofol, continued for 4 hours after cross-clamp release.
      Patients in the control group received saline administered in a similar fashion.
      MEASUREMENTS: Serum concentration of malondialdehyde (MDA) (from systemic and
      coronary sinus blood); systemic concentrations of interleukins 4, 6, 8, and 10;
      and systemic leukocyte functions (respiratory burst, phagocytosis, and beta(2)
      integrin expression) were measured up to 36 hours after reperfusion. RESULTS: A
      high serum malondialdehyde concentration was detected in the coronary sinus in
      control patients, 10 minutes after reperfusion; serum malondialdehyde was not
      detected in the coronary sinus at this time in patients who received propofol
      (41.4 [15.6-1,150] micromol/L v 0, p = 0.004). Interleukin-8 concentrations
      increased 2 and 4 hours after reperfusion in the control group. Interleukin-6
      concentrations were greater in the control group than the propofol group 4 hours
      after clamp release (289.1 [165.2-561] rhog/mL v 153.2 (58.2-280.3) rhog/mL,
      respectively, p = 0.003). Mean dose of propofol was 31.7 mg/kg during the study
      period. CONCLUSION: Clinically relevant concentrations of propofol may attenuate
      free radical-mediated and inflammatory components of myocardial reperfusion
      injury in patients undergoing elective coronary artery bypass graft surgery.

PMID- 15578471
TI  - Simvastatin blunts the increase of circulating adhesion molecules after coronary
      artery bypass surgery with cardiopulmonary bypass.
AB  - OBJECTIVES: Endothelial dysfunction has been shown to be a critical early
      component of organ injury after myocardial ischemia and reperfusion. Circulating
      levels of adhesion molecules have been regarded as a valid index of endothelial
      activation. Recent reports suggest that statins, widely used in the control of
      hypercholesterolemia, exert a protective effect on the endothelium reflected by a
      reduced level of circulating adhesion molecules. In this study, the effects of
      preoperative simvastatin treatment, at doses equivalent to those used orally for
      cholesterol control, were studied on plasma levels of VCAM-1, ICAM-1, and ELAM-1.
      DESIGN: A case-control study. SETTING: University hospital. PARTICIPANTS: Fifteen
      patients taking simvastatin with good control of cholesterol levels, 15 patients
      not responsive to the simvastatin treatment, and 15 normocholesterolemic patients
      (control) undergoing elective coronary artery bypass surgery. MEASUREMENTS AND
      MAIN RESULTS: The plasma levels of VACM-1, ICAM-1, and ELAM-1 were evaluated at
      baseline; during cardiopulmonary bypass; and 6 hours, 24 hours, and 48 hours
      postoperatively. In the late postoperative samples, the plasma levels of ICAM-1
      and ELAM-1 were lower in both simvastatin-treated patients compared with the
      control patients. No significant difference was found between the patients
      responsive to statin and those not responsive. Finally, no significant difference
      was found for VCAM-1 plasma levels between the control group and the 2 treatment
      groups. CONCLUSIONS: Pretreatment with simvastatin significantly reduces the
      increase of ICAM-1 and ELAM-1 after coronary artery bypass surgery, by a
      mechanism that seems not related to its efficacy in lowering cholesterol levels.

PMID- 15578472
TI  - Difficult intubation in pediatric cardiac anesthesia.
AB  - OBJECTIVE: The aim of this study was to investigate cases of difficult intubation
      in pediatric cardiac surgical patients and to evaluate the importance of
      associated congenital abnormalities. DESIGN: Retrospective analysis. SETTING:
      Departments of Anesthesiology and Pediatric Cardiovascular Surgery of a tertiary
      university hospital. PARTICIPANTS: All children undergoing congenital heart
      surgery. INTERVENTIONS: Patients who had difficult intubations according to their
      anesthetic charts were further evaluated from hospital files for demographic
      characteristics, associated congenital abnormalities, and perioperative airway
      and/or respiratory complications. MEASUREMENTS AND MAIN RESULTS: A total of 1,278
      pediatric patients with congenital heart disease were operated on from January
      1999 to July 2002. Difficult intubation was encountered in 16 cases (1.25%). Two
      of these were newborns, 11 were infants, and 3 were in the pediatric age group.
      Anterior larynx was the most common reason for difficult intubation (7 cases,
      43.7%). There were associated syndromes and/or other congenital abnormalities in
      8 children (50%). CONCLUSION: The likelihood of difficult intubation during
      pediatric cardiac surgery, especially in cases with other congenital pathologies
      should be kept in mind, and the anesthetic approach must be planned accordingly.

PMID- 15578473
TI  - Time to tracheal extubation after coronary artery surgery with isoflurane,
      sevoflurane, or target-controlled propofol anesthesia: a prospective, randomized,
      controlled trial.
AB  - OBJECTIVES: To determine if anesthesia with sevoflurane or target-controlled
      propofol reduced the time to tracheal extubation after coronary artery bypass
      graft surgery compared with isoflurane anesthesia. DESIGN: A 3-arm (isoflurane,
      sevoflurane, or propofol), randomized, controlled trial with patients and
      intensive care staff blinded to the drug allocation. SETTING: A single, tertiary
      referral hospital affiliated with the University of Melbourne. PARTICIPANTS:
      Three hundred sixty elective coronary artery surgery patients. INTERVENTIONS:
      Patients received either isoflurane (control group, 0.5%-2% end-tidal
      concentration), sevoflurane (1%-4% end-tidal concentration), or target-controlled
      infusion of propofol (1-8 microg/mL plasma target concentration) as part of a
      balanced, standardized anesthetic technique including 15 microg/kg of fentanyl.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was time to tracheal
      extubation. The median time to tracheal extubation for the propofol group was
      10.25 hours (interquartile range [IQR] 8.08-12.75), the sevoflurane group 9.17
      hours (IQR 6.25-11.25), and the isoflurane group 7.67 hours (IQR 6.25-9.42).
      Intraoperatively, the propofol group required less vasopressor (p = 0.002) and
      more vasodilator therapy (nitroglycerin p = 0.01, nitroprusside p = 0.002). There
      was no difference among the groups in time to intensive care unit discharge.
      CONCLUSIONS: The median time to tracheal extubation was significantly longer for
      the target-controlled propofol group. A significantly greater number in this
      group required the use of a vasodilator to control intraoperative hypertension.

PMID- 15578474
TI  - Cardiopulmonary bypass reduces the minimum alveolar concentration for isoflurane.
AB  - OBJECTIVE: The purpose of this investigation was to determine the influence of
      cardiopulmonary bypass (CPB) on the minimum alveolar concentration (MAC) of
      isoflurane in a rat model of CPB. DESIGN: Prospective. SETTING: University
      research laboratory. PARTICIPANTS: Sprague-Dawley rats. INTERVENTIONS: Using tail
      clamp methodology, the pre- and post-CPB MAC for isoflurane was studied. METHODS
      AND MAIN RESULTS: Rats were anesthetized with isoflurane, intubated, ventilated,
      and surgically prepared for CPB, after which they were randomized to either Sham
      operated or CPB groups. The CPB group (n = 10) underwent 90 minutes of
      normothermic nonpulsatile CPB. The Sham group (n = 13) were cannulated but did
      not undergo CPB. Pre- and post-CPB MAC determinations were compared within groups
      using a paired Student t test. The CPB group had a pre-CPB baseline isoflurane
      MAC of 1.09% +/- 0.11% versus 1.09% +/- 0.08% in the Sham group (p = 0.90).
      Twenty minutes after CPB, the CPB group exhibited a decrease in MAC to 0.98% +/-
      0.14% (p = 0.0026, compared with baseline). The MAC in the Sham group was
      unchanged (p = 0.5852, compared with baseline). Two hours after CPB, the MAC in
      the CPB group remained lower compared with baseline at 0.99% +/- 0.14% (p =
      0.0032). CONCLUSIONS: CPB resulted in a small (10%) but significant reduction in
      the MAC for isoflurane. The mechanism behind this reduction in MAC is not clear
      but may be related to CPB-induced cerebral injury.

PMID- 15578475
TI  - Use of cerebrospinal fluid drainage catheters during single-stage
      transmediastinal repair of ascending/descending aortic aneurysms.

PMID- 15578476
TI  - Perioperative management of pacemaker implantation for congenital complete heart
      block.

PMID- 15578477
TI  - Desflurane and remifentanil use during resection of a cardiac pheochromocytoma.

PMID- 15578478
TI  - Simultaneous repair of bilateral multiple emphysematous bullae with a secundum
      atrial septal defect.

PMID- 15578479
TI  - Left atrial thrombus formation early after mitral valve replacement.

PMID- 15578480
TI  - Salvage application of secondary blood cardioplegia in intractable ventricular
      fibrillation.

PMID- 15578481
TI  - Cerebral function monitors during pediatric cardiac surgery: can they make a
      difference?

PMID- 15578482
TI  - Case 5--2004: Transesophageal echocardiography-guided insertion of a pulmonary
      artery catheter.

PMID- 15578483
TI  - Pro: Exchange transfusion is required for sickle cell trait patients undergoing
      cardiopulmonary bypass.

PMID- 15578484
TI  - Con: Exchange transfusion is not required for sickle cell trait patients
      undergoing cardiopulmonary bypass.

PMID- 15578485
TI  - Computed tomography reveals an unusual complication in a patient having undergone
      coronary artery bypass surgery.

PMID- 15578486
TI  - An abnormal echo-free space behind the left atrium.

PMID- 15578487
TI  - Radio-opaque foreign body on a postoperative chest X-ray.

PMID- 15578490
TI  - Defective triple-lumen catheter.

PMID- 15578491
TI  - Decreased release of endothelin after OPCAB: implications of the evidence.

PMID- 15578492
TI  - Yet another venous air embolism!

PMID- 15578493
TI  - Correlation of BIS with Tet spells.

PMID- 15578500
TI  - Data from arrays: an embarrassment of riches.

PMID- 15578501
TI  - Image of the month.

PMID- 15578502
TI  - Is there endoscopic capacity to provide colorectal cancer screening to the
      unscreened population in the United States?
AB  - BACKGROUND & AIMS: Screening rates for colorectal cancer remain low compared with
      screening rates for other cancers. The size of the unscreened population and the
      capacity to provide widespread screening are unknown. We estimated the number of
      average-risk persons aged 50 years or older not screened for colorectal cancer,
      the number of procedures required for this population, and the endoscopic
      capacity to satisfy this unmet need. METHODS: Using data from the US Census
      Bureau and the Centers for Disease Control and Prevention's National Health
      Interview Survey, we designed a forecasting model to estimate the number of
      persons in the United States currently not screened for colorectal cancer and the
      number of examinations needed to screen these persons. Test need was compared
      with available capacity, based on results from the national Survey of Endoscopic
      Capacity, assuming different proportions of available capacity were used for
      colorectal cancer screening. RESULTS: Approximately 41.8 million average-risk
      people aged 50 years or older have not been screened for colorectal cancer
      according to national guidelines. Sufficient capacity exists to screen the
      unscreened population within 1 year using fecal occult blood testing followed by
      diagnostic colonoscopy for positive tests. Depending on the proportion of
      available capacity used for colorectal cancer screening, it could take up to 10
      years to screen the unscreened population using flexible sigmoidoscopy or
      colonoscopy. CONCLUSIONS: The capacity exists for widespread screening with fecal
      occult blood testing. The capacity for screening with flexible sigmoidoscopy or
      colonoscopy depends on the proportion of available capacity used for colorectal
      cancer screening.

PMID- 15578503
TI  - How many endoscopies are performed for colorectal cancer screening? Results from
      CDC's survey of endoscopic capacity.
AB  - BACKGROUND & AIMS: Estimates of the current number of endoscopic colorectal
      cancer screening and follow-up examinations being performed are limited. A
      national study was therefore conducted among US physician practices. METHODS:
      Approximately 1800 medical practices were surveyed from a list of all practices
      known to have purchased or leased lower endoscopic equipment between 1996 and
      2000. Questions were asked regarding the current number of lower endoscopic
      procedures performed and the potential maximum number that could be performed.
      RESULTS: In 2002, a total of 8207 practices reported performing flexible
      sigmoidoscopy or colonoscopy in the United States. Gastroenterologists performed
      43.7% (95% confidence interval [CI], 37.2-50.2) of all sigmoidoscopies and 82.5%
      (95% CI, 80.3-84.7) of all colonoscopies. Primary care physicians performed 24.9%
      (95% CI, 20.3-29.5) of all sigmoidoscopies and 2.0% (95% CI, 1.4-2.6) of all
      colonoscopies. All physicians combined performed approximately 2.8 million (95%
      CI, 2.4-3.1) flexible sigmoidoscopies and 14.2 million (95% CI, 12.1-16.4)
      colonoscopies but reported that they could increase to approximately 9.5 million
      flexible sigmoidoscopies (95% CI, 8.4-10.5) and 22.4 million colonoscopies (95%
      CI, 20.1-24.8) in 1 year. CONCLUSIONS: Approximately 2.8 million flexible
      sigmoidoscopies and 14.2 million colonoscopies were estimated to have been
      performed in 2002. Physicians reported that they could perform an additional 6.7
      million flexible sigmoidoscopies and 8.2 million colonoscopies in 1 year. These
      additional procedures could be used for the unscreened population and should be
      considered in the estimate of the national capacity to provide colorectal cancer
      screening to all eligible persons in the United States.

PMID- 15578504
TI  - The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA:
      implications for chemosensitivity and resistance.
AB  - BACKGROUND & AIMS: Recent evidence suggests that patients with advanced
      microsatellite unstable (MSI) colorectal cancers lack a survival benefit with 5
      fluorouracil (5-FU)-based chemotherapy. Additionally, tumor cells with MSI
      (caused by defective DNA mismatch repair) are more resistant to 5-FU in culture
      compared with microsatellite stable cells, despite similar amounts of 5-FU
      incorporation into the cell's DNA. We examined whether the component of the DNA
      mismatch repair (MMR) system that normally recognizes single base pair mismatches
      could specifically recognize 5-FU incorporated into DNA as a potential mechanism
      for chemosensitivity. METHODS: We synthesized oligonucleotides with and without
      incorporated 5-FU and created oligonucleotides with a single base pair mismatch
      (as a positive control) to perform electromobility gel shift assays (EMSA) with a
      purified, baculovirus-synthesized hMutS alpha MMR complex. We also utilized
      surface plasmon resonance to measure relative binding differences between the
      oligonucleotides and hMutS alpha in real time. RESULTS: Using EMSA, we
      demonstrate that hMutS alpha recognizes and binds 5-FU-modified DNA. The reaction
      is specific as added ATP dissociates the hMutS alpha complex from the 5-FU
      modified strand. Using surface plasmon resonance, we demonstrate greater binding
      between hMutS alpha and 5-FU-modified DNA compared with complementary DNA or DNA
      containing a C/T mismatch. CONCLUSIONS: The MMR complex hMutS alpha specifically
      recognizes and binds to 5-FU-modified DNA. Because MMR components are required
      for the induction of apoptosis by many DNA-damaging agents, the chemosensitivity
      of 5-FU for patients with advanced colorectal cancer may be in part due to
      recognition of 5-FU incorporated into tumor DNA by the MMR proteins.

PMID- 15578505
TI  - Disse of the space of Disse.

PMID- 15578506
TI  - Contributions of gastric volumes and gastric emptying to meal size and postmeal
      symptoms in functional dyspepsia.
AB  - BACKGROUND & AIMS: The aim was to assess relative contributions of gastric
      volumes (GV) and gastric emptying (GE) to meal size and postprandial symptoms in
      patients with functional dyspepsia. METHODS: Patients with chronic upper
      gastrointestinal symptoms were prospectively evaluated. GV during fasting and
      after 300 mL Ensure was measured with 99m Tc-single-photon emission computed
      tomography imaging and solid GE (99m Tc-egg) by scintigraphy. Maximum tolerated
      volume (MTV) and symptoms were measured after Ensure challenge. RESULTS: Of 57
      adult patients evaluated, 39 (23 women, 16 men) met Rome II criteria for
      functional dyspepsia and had no other diagnosis to account for dyspepsia. The
      most frequent symptoms were abdominal pain (90%), pain predominantly after meals
      (76%), nausea (85%), and early fullness after meals (79%). Relative to
      established laboratory normal values, MTV was abnormal in 82%, aggregate symptom
      score >209 in 72%, GE (at 1 hour) accelerated in 41%, GE (at 4 hours) delayed in
      41%, and postmeal GV reduced in 52%. Lower body mass was associated with lower
      MTV and higher postchallenge symptoms. Lower fasting (not postprandial) GV and
      faster GE were independent predictors of lower MTV, explaining 18% of the
      variance after adjusting for body weight (32% of variance). GE was an independent
      predictor of postchallenge symptoms (10% of variance) after adjusting for volume
      ingested (10%), age (20%), and weight (10%). CONCLUSIONS: In adults with
      functional dyspepsia seen in a tertiary referral practice, decreased meal size
      and postmeal symptoms are associated with low fasting GV and faster GE. These
      data provide physiologic targets for ameliorating symptoms of functional
      dyspepsia.

PMID- 15578507
TI  - Effect of acute physical and psychological stress on gut autonomic innervation in
      irritable bowel syndrome.
AB  - BACKGROUND & AIMS: Stress is an important causative factor in irritable bowel
      syndrome (IBS). It remains unknown whether stress-related changes in gut function
      are mediated by altered autonomic efferent gut-specific innervation. We studied
      the effect of acute physical and psychological stress on autonomic innervation
      and visceral sensitivity in healthy volunteers and patients with IBS. METHODS:
      Twenty-four patients (20 women) with constipation-predominant IBS and 12 healthy
      volunteers (8 women) underwent either physical (cold water hand immersion) or
      psychological (dichotomous listening) stress on separate occasions. Assessments
      included stress perception (visual analogue scale), gut-specific autonomic
      innervation (rectal mucosal blood flow [RMBF] by laser Doppler flowmetry), and
      viscerosomatic sensitivity (anal and rectal electrosensitivity). RESULTS:
      Patients with IBS had a heightened baseline perception of stress (P < .01). RMBF
      decreased during physical stress (29.6% +/- 2.8% and 28.7% +/- 3.9%) and
      psychological stress (24.4% +/- 2.1% and 23.5% +/- 4.3%) in patients with IBS and
      controls, respectively (mean +/- SEM). During physical stress, rectal perception
      (23.2% +/- 6% vs .6% +/- 3% [IBS vs control group, P < .05]) and rectal pain
      thresholds (27.0% +/- 4% vs 1.3% +/- 5%, P < .001) decreased in patients with IBS
      only. Psychological stress reduced thresholds for rectal perception (19.4% +/- 6%
      vs 8% +/- 6%, P < .01) and rectal pain (28.4% +/- 4% vs 3.4% +/- 3.8%, P < .001)
      in patients with IBS only. Acute stress elevated anal perception thresholds in
      patients with IBS but not controls (physical stress: 14.7% +/- 14% vs -9.3% +/-
      11%, P < .05; psychological stress: 24.7% +/- 9% vs 11% +/- 11%, P < .05).
      CONCLUSIONS: Acute stress alters gut-specific efferent autonomic innervation in
      both controls and patients with IBS, although normalization is delayed in IBS. By
      contrast, only patients with IBS show heightened visceral sensation, suggesting
      involvement of a different regulatory mechanism, either central or peripheral.

PMID- 15578508
TI  - Serum markers detect the presence of liver fibrosis: a cohort study.
AB  - BACKGROUND & AIMS: Histologic examination of a liver biopsy specimen is regarded
      as the reference standard for detecting liver fibrosis. Biopsy can be painful and
      hazardous, and assessment is subjective and prone to sampling error. We developed
      a panel of sensitive automated immunoassays to detect matrix constituents and
      mediators of matrix remodeling in serum to evaluate their performance in the
      detection of liver fibrosis. METHODS: In an international multicenter cohort
      study, serum levels of 9 surrogate markers of liver fibrosis were compared with
      fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic
      liver disease. Discriminant analysis of a test set of samples was used to
      identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide
      of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was
      subsequently evaluated using a validation set of biopsy specimens and serum
      samples. RESULTS: The algorithm detected fibrosis (sensitivity, 90%) and
      accurately detected the absence of fibrosis (negative predictive value for
      significant fibrosis, 92%; area under the curve of a receiver operating
      characteristic plot, .804; standard error, .02; P < .0001; 95% confidence
      interval, .758-.851). Performance was excellent for alcoholic liver disease and
      nonalcoholic fatty liver disease. The algorithm performed equally well in
      comparison with each of the pathologists. In contrast, pathologists' agreement
      over histologic scores ranged from very good to moderate (kappa = .97-.46).
      CONCLUSIONS: Assessment of liver fibrosis with multiple serum markers used in
      combination is sensitive, specific, and reproducible, suggesting they may be used
      in conjunction with liver biopsy to assess a range of chronic liver diseases.

PMID- 15578509
TI  - Radiofrequency ablation improves prognosis compared with ethanol injection for
      hepatocellular carcinoma < or =4 cm.
AB  - BACKGROUND & AIMS: The aim of this study was to compare the clinical outcome of
      percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol
      injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4
      cm or less. METHODS: A total of 157 patients with 186 HCCs 4 cm or less were
      randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in
      the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of
      complete tumor necrosis, overall survival, local tumor progression, additional
      new tumors, and cancer-free survival were compared across 3 groups. RESULTS: The
      rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the
      higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were
      required to achieve complete tumor necrosis in the RF group than in the other 2
      groups (P < .01). The local tumor progression rate was lowest in the RF group (vs
      the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037).
      The overall survival rate was highest in the RF group (vs the conventional PEI
      group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free
      survival rate was highest in the RF group (vs the conventional PEI group, P =
      .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined
      that tumor size, tumor differentiation, and the method of treatment (RF vs both
      methods of PEI) were significant factors in relation to local tumor progression,
      overall survival, and cancer-free survival. CONCLUSIONS: The results show that RF
      ablation yielded better clinical outcomes than conventional and higher-dose PEI
      in treating HCC 4 cm or less.

PMID- 15578510
TI  - Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic
      hepatitis C and normal aminotransferase levels.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis C and persistently normal
      alanine aminotransferase (ALT) levels have been routinely excluded from large
      randomized treatment trials; consequently, the efficacy and safety of antiviral
      therapy in this population are unknown. METHODS: Patients with at least 3 normal
      ALT values over an 18-month period were randomized (3:3:1) to treatment with
      peginterferon alfa-2a 180 mug/wk plus ribavirin 800 mg/day for 24 weeks (212
      patients), the same combination for 48 weeks (210 patients), or no treatment (69
      patients) in a multinational study. All patients were monitored for 72 weeks. The
      primary measure of efficacy was sustained virologic response (SVR), defined as
      undetectable serum hepatitis C virus (HCV) RNA by qualitative polymerase chain
      reaction at the end of 24 weeks of untreated follow-up. RESULTS: No patient
      cleared HCV RNA in the untreated control group. SVR rates of 30% and 52% were
      obtained in the 24- and 48-week treatment groups, respectively. In patients
      infected with HCV genotype 1, SVR rates of 13% and 40% were obtained with 24 and
      48 weeks of treatment, respectively (P < .0001). In patients infected with
      genotypes 2 or 3, SVR rates were 72% and 78% with 24 and 48 weeks of treatment,
      respectively (P = .452). Treatment-related flares in ALT activity were not
      observed. CONCLUSIONS: The efficacy and safety of peginterferon alfa-2a and
      ribavirin combination therapy in patients with chronic hepatitis C and
      persistently normal ALT levels are similar to that in patients with elevated ALT
      levels. The indication for treatment of hepatitis C can be evaluated
      independently from baseline ALT activity.

PMID- 15578511
TI  - Clinical relevance of hepatitis B virus genotype in children with chronic
      infection and hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The aim of this study was to investigate the influence of
      hepatitis B virus (HBV) genotypes on the clinical outcome of chronic childhood
      HBV infection and hepatocellular carcinoma (HCC). METHODS: A total of 460 HBV
      carrier children were followed-up for 15 years and 26 children with HBV-related
      HCC were recruited. HBV genotyping was examined at enrollment and the latest
      follow-up of these carrier children and at diagnosis in HCC children. Viral load
      was checked at enrollment for the carrier children. These carriers were grouped
      based on their initial hepatitis B e antigen (HBeAg) and antibody to hepatitis B
      e antigen (anti-HBe) status. The HBeAg positive (+) group was divided further
      into an HBeAg(+/+) group and HBeAg(+/-) group, depending on whether spontaneous
      HBeAg seroconversion occurred during the follow-up period. RESULTS: Genotype B
      constituted 73%, 86%, and 76% in the HBeAg(+/+), HBeAg(+/-), and anti-HBe(+)
      groups, respectively. Genotype C was found in 27%, 8%, and 6% in the HBeAg(+/+),
      HBeAg(+/-), and anti-HBe(+) group, respectively. Genotype C carriers were more
      prevalent in the HBeAg(+/+) group than the other 2 groups (P = .01), and had a
      delayed HBeAg seroconversion compared with the genotype B carriers (P < .001).
      Changes of genotype during the follow-up period were rare (2.8%). In those with
      HCC, genotype B was also the major type (74%). There was no difference in the
      baseline viral load between genotypes B and C. CONCLUSIONS: Although HBV genotype
      B dominates in children with chronic HBV infection and HCC in Taiwan, genotype C
      delays HBeAg seroconversion in pediatric chronic HBV infection.

PMID- 15578512
TI  - The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor
      function.
AB  - BACKGROUND & AIMS: Visceral mechanoreceptors are critical for perceived
      sensations and autonomic reflex control of gastrointestinal function. However,
      the molecular mechanisms underlying visceral mechanosensation remain poorly
      defined. Degenerin/epithelial Na+ channel (DEG/ENaC) family ion channels are
      candidate mechanosensory molecules, and we hypothesized that they influence
      visceral mechanosensation. We examined the influence of the DEG/ENaC channel
      ASIC1 on gastrointestinal mechanosensory function, on gastric emptying, and on
      fecal output. We also compared its role in gastrointestinal and somatic sensory
      function. METHODS: To assess the role of ASIC1 we studied wild-type and ASIC1-/-
      mice. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot
      analysis determined expression of ASIC1 messenger RNA and protein in vagal and
      spinal sensory ganglia. Colonic, gastroesophageal, and cutaneous afferent fibers
      were characterized by functional subtype and their mechanical stimulus-response
      relationships were determined. Gastric emptying was determined by using a 13CO2
      breath test. Behavioral tests assessed somatic mechanical and thermal
      sensitivity. RESULTS: ASIC1 was expressed in sensory ganglia and was lost after
      disruption of the ASIC1 gene. Loss of ASIC1 increased mechanosensitivity in all
      colonic and gastroesophageal mechanoreceptor subtypes. In addition, ASIC1-/- mice
      showed almost double the gastric emptying time of wild-type mice. In contrast,
      loss of ASIC1 did not affect function in any of the 5 types of cutaneous
      mechanoreceptors, nor did it affect paw withdrawal responses or fecal output.
      CONCLUSIONS: ASIC1 influences visceral but not cutaneous mechanoreceptor
      function, suggesting that different mechanisms underlie mechanosensory function
      in gut and skin. The role of ASIC1 is highlighted by prolonging gastric emptying
      of a meal in ASIC1-/- animals.

PMID- 15578513
TI  - Intestinal surgical resection disrupts electrical rhythmicity, neural responses,
      and interstitial cell networks.
AB  - BACKGROUND & AIMS: Surgical manipulations of the gastrointestinal (GI) tract,
      including intestinal resection and anastomosis, lead to motility disorders
      including a decrease in phasic and segmental contractions. The aims of the
      present investigation were to determine mechanisms underlying the loss of
      motility in a murine model of intestinal resection and to follow-up the recovery
      of intestinal motility after surgical manipulation. METHODS: Segments of ileum
      were removed from mice and the intestines were reconstructed. After surgery, the
      structure and activity of the ileal muscles, 0-5 cm oral and aboral to the site
      of resection, were examined at 5 and 24 hours with intracellular microelectrode
      recordings, isometric force measurements, Kit-like immunohistochemistry, and
      electron microscopy. RESULTS: Five hours after surgery there was loss of
      electrical slow waves and phasic contractions in muscles near the site of
      resection. This defect decreased as a function of distance above and below the
      resection. Tissues in the affected region were poorly responsive to carbachol and
      transmural nerve stimulation. Kit-like immunohistochemistry revealed disruption
      in interstitial cell of Cajal (ICC) networks at the level of the myenteric and
      deep muscular plexuses. Lesions in ICCs decreased with distance from the site of
      resection. Slow waves and mechanical activity recovered at the site of
      anastomosis 24 hours after surgery and recovered more rapidly when tissues were
      incubated in the inducible nitric oxide synthase (iNOS) inhibitor, L-N6 -(1
      Iminoethyl) lysine hydrochloride (L-NIL). CONCLUSIONS: Loss of intestinal
      motility after surgery is associated with acute disruption of ICC networks, slow
      waves, and phasic contractions. This activity partially recovered within 24 hours
      after surgery.

PMID- 15578514
TI  - Innate immune system plays a critical role in determining the progression and
      severity of acetaminophen hepatotoxicity.
AB  - BACKGROUND & AIMS: Inflammatory mediators released by nonparenchymal inflammatory
      cells in the liver have been implicated in the progression of acetaminophen
      (APAP) hepatotoxicity. Among hepatic nonparenchymal inflammatory cells, we
      examined the role of the abundant natural killer (NK) cells and NK cells with T
      cell receptors (NKT cells) in APAP-induced liver injury. METHODS: C57BL/6 mice
      were administered a toxic dose of APAP intraperitoneally to cause liver injury
      with or without depletion of NK and NKT cells by anti-NK1.1 monoclonal antibody
      (MAb). Serum alanine transaminase (ALT) levels, liver histology, hepatic
      leukocyte accumulation, and cytokine/chemokine expression were assessed. RESULTS:
      Compared with APAP-treated control mice, depletion of both NK and NKT cells by
      anti-NK1.1 significantly protected mice from APAP-induced liver injury, as
      evidenced by decreased serum ALT level, improved survival of mice, decreased
      hepatic necrosis, inhibition of messenger RNA (mRNA) expression for interferon
      gamma (IFN-gamma), Fas ligand (FasL), and chemokines including KC (Keratinocyte
      derived chemokine); MIP-1 alpha (macrophage inflammatory protein-1 alpha); MCP-1
      (monocyte chemoattractant protein-1); IP-10 (interferon-inducible protein); Mig
      (monokine induced by IFN-gamma) and decreased neutrophil accumulation in the
      liver. Hepatic NK and NKT cells were identified as the major source of IFN-gamma
      by intracellular cytokine staining. APAP induced much less liver injury in Fas
      deficient (lpr) and FasL-deficient (gld) mice compared with that in wild-type
      mice. CONCLUSIONS: NK and NKT cells play a critical role in the progression of
      APAP-induced liver injury by secreting IFN-gamma, modulating chemokine production
      and accumulation of neutrophils, and up-regulating FasL expression in the liver,
      all of which may promote the inflammatory response of liver innate immune system,
      thus contributing to the severity and progression of liver injury downstream of
      the metabolism of APAP and depletion of reduced glutathione (GSH) in hepatocytes.

PMID- 15578515
TI  - The role of notch signaling in the development of intrahepatic bile ducts.
AB  - BACKGROUND & AIMS: Mutations in Jagged1 , a Notch ligand, cause Alagille syndrome
      (AGS), a disorder characterized by a paucity of intrahepatic bile ducts (IHBD).
      The mechanism underlying the contribution of the Notch signaling pathway to IHBD
      formation, however, remains unknown. Here we investigated the role of Notch
      signaling in IHBD development. METHODS: The expression patterns of Jagged1,
      Notch2, and Hes1 during mouse liver development were analyzed by semiquantitative
      reverse-transcription polymerase chain reaction (RT-PCR), immunoblot, and
      immunohistochemistry. The hepatocyte maturation level and IHBD development were
      studied in Hes1 null mice in comparison with wild-type mice. The effect of
      Jagged1 on biliary differentiation was assessed by using an in vitro 2-cell
      coculture system with WB-F344 cells, a cell line derived from normal adult rat
      liver. RESULTS: Jagged1 was expressed in the portal mesenchyme during the
      neonatal period. During the same period, Notch2 and Hes1 expression was observed
      in the biliary epithelial cells adjacent to the Jagged1-positive cells. During
      ductal plate remodeling, Notch2 and Hes1 were up-regulated exclusively in the
      biliary epithelial cells that form tubular structures. In contrast, the tubular
      formation of IHBD was completely absent in Hes1 null mice. Coculture with Balb3T3
      cells stably overexpressing Jagged1 induced transactivation of the Hes1 promoter
      and increased expression of biliary lineage markers, such as cytokeratin-19 and
      gamma-glutamyl transpeptidase, in WB-F344 cells. CONCLUSIONS: Our results suggest
      that Notch signaling has an important role in the differentiation of biliary
      epithelial cells and is essential for their tubular formation during IHBD
      development.

PMID- 15578516
TI  - Translational regulation of XIAP expression and cell survival during hypoxia in
      human cholangiocarcinoma.
AB  - BACKGROUND & AIMS: Tumor progression is promoted by the ability of tumor cells to
      resist adverse environmental conditions such as hypoxia. We have shown that
      translational dysregulation contributes to transformed cell growth in malignant
      cholangiocytes. Translational regulation of gene expression can contribute to an
      immediate and rapid response to environmental changes such as hypoxia. Thus, our
      aims were to assess translational mechanisms involved in cell survival during
      hypoxia and to identify specific translationally regulated proteins involved in
      the cellular response to hypoxia. METHODS: Cell viability and apoptosis in
      response to hypoxia were assessed in human cholangiocarcinoma cells.
      Translational processes were deregulated by cycloheximide or rapamycin or by
      targeted deletion of eukaryotic initiation factor (eIF)-4E, a rate-limiting
      translational initiation factor using small interfering RNA (siRNA). A protein
      antibody microarray was used to screen for eIF-4E-dependent proteins expressed
      during hypoxia. Expression of the X-linked inhibitor of apoptosis (XIAP) was
      decreased using siRNA. RESULTS: Malignant cholangiocytes are resistant to hypoxia
      induced apoptosis. Furthermore, cell survival during hypoxia required protein
      translation. eIF-4E was over expressed in malignant cholangiocytes. Reduction in
      eIF-4E expression by siRNA decreased tumor cell resistance to hypoxia, increased
      caspase-3 activation and apoptosis, and decreased cell survival compared with
      controls. XIAP was identified as a translationally regulated protein expressed
      during hypoxia. Modulation of XIAP expression by siRNA decreases cell death
      during hypoxia in vitro and in vivo. CONCLUSIONS: Human cholangiocarcinoma cells
      are highly resistant to hypoxia. Translational regulation of survival proteins
      such as XIAP is a mechanism mediating cholangiocarcinoma survival during hypoxia.

PMID- 15578517
TI  - The role of AMP-activated protein kinase in the action of ethanol in the liver.
AB  - BACKGROUND & AIMS: Our previous work has shown that ethanol induces the fatty
      acid synthesis pathway by activation of sterol regulatory element-binding protein
      1 (SREBP-1). In the present study, we studied the mechanisms of this activation
      by identifying a new target of ethanol, AMP-activated protein kinase (AMPK).
      METHODS: The effects of ethanol on AMPK, acetyl-CoA carboxylase (ACC), and SREBP
      1 were assessed in rat hepatic cells and in the livers of ethanol-fed mice.
      RESULTS: In rat hepatoma H4IIEC3 or McA-RH 7777 cell lines, ethanol-induced
      transcription of an SREBP-regulated promoter was suppressed by the presence of 5
      aminoimidazole-4-carboxamide ribonucleoside (AICAR) or metformin, 2 known AMPK
      activators. Consistent with this, over expression of a constitutively active form
      of AMPK blocked the effect of ethanol, whereas coexpression of a dominant
      negative form of AMPK augmented the effect. Moreover, activation of AMPK by
      metformin or AICAR largely blocked the ability of ethanol to increase levels of
      mature SREBP-1 protein. These findings suggest that the effect of ethanol on
      SREBP-regulated promoter activation was partially mediated through AMPK
      inhibition. We further demonstrated that AMPK was inhibited by ethanol in hepatic
      cells. In parallel, ethanol increased the activity of ACC and suppressed the rate
      of palmitic acid oxidation. Finally, feeding mice a low-fat diet with ethanol
      resulted in significantly reduced hepatic AMPK activity, increased ACC activity,
      and enhanced malonyl CoA content. CONCLUSIONS: Taken together, our findings
      suggest that AMPK may play a key role in regulating the effects of ethanol on
      SREBP-1 activation, fatty acid metabolism, and development of alcoholic fatty
      liver.

PMID- 15578518
TI  - Clinical management of pouchitis.

PMID- 15578519
TI  - BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular
      level.
AB  - BACKGROUND & AIMS: Anorectal melanoma (AM) is a rare but highly malignant tumor,
      displaying histologic and immunohistochemical features very similar to cutaneous
      melanoma (CM). Because BRAF mutations were recently identified in the majority of
      CM and nevi, we investigated AM for BRAF mutations and mutations of NRAS , an
      additional component of the MAPK-signalling pathway. METHODS: DNA from formalin
      fixed and paraffin-embedded AM was PCR amplified and sequenced. RESULTS: We
      detected BRAF mutations in 2 of 19 cases and NRAS mutations in none of the cases.
      Mutations in exon 15 of BRAF were present in only 1 tumor (1 of 19 cases). The
      A1800T base exchange represented a novel mutation and resulted in a K600N
      transition in an AM from a 96-year-old white man who presented with rectal
      bleeding and painful sitting of a few weeks' duration. The second positive AM
      case, a 69-year-old white man who presented with painless rectal bleeding and
      clinical symptoms of an intestinal constipation showed a novel missense mutation
      (C1327T leading to R443W conversion) in BRAF exon 11. None of the AM cases
      displayed the oncogenic V599E mutation preponderating in CM. CONCLUSIONS: With
      regard to the frequency of V599E BRAF mutations, AM significantly differs from CM
      (P < or = .0001), which suggests that BRAF mutations distinguish anorectal from
      cutaneous melanoma at the molecular level.

PMID- 15578520
TI  - Colorectal cancer vaccines: principles, results, and perspectives.
AB  - In the search for novel therapeutic approaches to treat patients with colorectal
      carcinoma, anticancer vaccination holds promise. A large body of preclinical and
      clinical evidence has demonstrated that the immune system can be polarized
      against malignant cells by means of several active specific immunotherapy
      strategies. Although no vaccination regimen can be currently recommended outside
      clinical trials, tumor response and immunologic findings observed in animal
      models and humans prompt researchers to explore further the antitumor potential
      of such biotherapy in an effort to reproduce in a larger set of patients the
      cascade of molecular events that characterizes the successful tumor immune
      rejection currently observed in a minority of vaccinated subjects. In this work,
      we summarize the principles and the main results of cancer vaccine strategies so
      far implemented for the treatment of patients with colorectal carcinoma. We also
      discuss the most recent preclinical tumor immunology insights that might change
      the way to design the next generation of cancer vaccines, hopefully improving the
      effectiveness of such a biotherapeutic approach.

PMID- 15578521
TI  - American Gastroenterological Association. Presidential address.

PMID- 15578522
TI  - Colonoscopy capacity: Can we build it? Will they come?

PMID- 15578523
TI  - Mechanisms underlying meal-induced symptoms in functional dyspepsia.

PMID- 15578525
TI  - What is the best management strategy for achalasia?

PMID- 15578524
TI  - Assessing fibrosis without a liver biopsy: are we there yet?

PMID- 15578526
TI  - Tissue glue for the endoscopist: healing by sealing.

PMID- 15578527
TI  - IPMN: not a new kid on the block anymore.

PMID- 15578528
TI  - Minimal hepatic encephalopathy: should we start treating it?

PMID- 15578533
TI  - Genes for gestational iron loading?

PMID- 15578535
TI  - Chronic diarrhea.

PMID- 15578536
TI  - Patients with primary biliary cirrhosis make anti-viral and anti-mitochondrial
      antibodies to mouse mammary tumor virus.

PMID- 15578538
TI  - Preventive therapy for complicated diverticular disease of the colon: looking for
      a correct therapeutic approach.

PMID- 15578539
TI  - Leptin reduces the development of the initial precancerous lesions induced by
      azoxymethane in the rat colonic mucosa.

PMID- 15578545
TI  - Development and validation of a second-generation metal-on-metal bearing:
      laboratory studies and analysis of retrievals.
AB  - This paper summarizes hip simulator and retrieval studies that were done to
      optimize 1 design of a second-generation metal-on-metal hip replacement. It was
      determined that clearance is the first key parameter controlling wear behaviour.
      The clearance should be as small as possible while as large as necessary to avoid
      any equatorial contact leading to clamping of the articulation. The minimum
      clearance should be investigated for each different design. Carbon concentration
      should be in the range 0.20-0.25% as high carbon concentration alloys have
      systematically a lower wear rate than low carbon alloys. The wear of clinically
      retrieved implants confirms the predicted low wear of this implant and confirms
      the importance of the clearance and the type of cobalt-chrome alloy.

PMID- 15578546
TI  - A consensus paper on metal ions in metal-on-metal hip arthroplasties.
AB  - The number of metal-on-metal bearings used clinically continues to increase,
      particularly in young, active patients. The single greatest concern with the use
      of a metal-on-metal bearing continues to be the elevated levels of metal ions
      measurable in patients' blood and urine following implantation. There are
      multiple complex issues associated with the analysis of metal ions, including
      collection techniques, analysis, statistical methodologies, and reporting of
      results. To date, the literature on this topic has been characterized by
      significant variability in all of these factors. This paper seeks to establish a
      consensus among 3 investigators who have been working in this area and to offer
      guidelines on the complex methodology involved in the evaluation of metal
      concentration in patients following metal-on-metal hip arthroplasties.

PMID- 15578547
TI  - Metal-on-metal surface arthroplasty with a cemented femoral component: a 7-10
      year follow-up study.
AB  - Forty-two McMinn metal-on-metal surface arthroplasties were implanted in 23 males
      and 16 females, average age 47.5 years old. The overall survivorship at 7 years
      was 79%; with any reoperation surgery as endpoint, 80%; and 93%; with aseptic
      loosening of the socket and femoral component, respectively. The average Surface
      Arthroplasty Risk Index of patients who had failed or were at risk of failing on
      the femoral side was significantly greater than for the rest of the cohort, 3.9
      versus 1.9. The overall survivorship of the McMinn component was unacceptably
      low, with the majority of failures occurring with the cemented acetabular
      components. The recent reintroduction of surface arthroplasty of the hip using
      metal-on-metal bearings and cementless acetabular components may benefit young
      patients with hip arthritis with appropriate patient selection.

PMID- 15578548
TI  - Cementless metal-on-metal hip arthroplasty in patients less than 50 years of age:
      comparison with a matched control group using ceramic-on-polyethylene after a
      minimum 5-year follow-up.
AB  - Thirty-nine cementless hip arthroplasties using metal-on-metal articulation were
      consecutively implanted in 30 patients less than 50 years of age and compared
      with a matched control group (by age, diagnosis, Devane activity, and Harris hip
      scores) of cementless arthroplasties using ceramic-on-polyethylene articulation.
      The Harris hip score at follow-up (minimum 5 years) for the metal-on-metal was
      94.9 (range, 74-100). After the same follow-up, the results of the ceramic-on
      polyethylene were significantly worse: 9 osteolyses and 7 surgical revisions
      related to wear (none in the metal-on-metal). Five-year survival rates were 97%
      +/-2% for the ceramic-on-polyethylene and 100% for the metal-on-metal. The metal
      on-metal may be recommended to prevent wear problems in younger and more active
      patients; however, a longer follow-up is required to confirm this encouraging
      data.

PMID- 15578549
TI  - An American experience with metal-on-metal total hip arthroplasties: a 7-year
      follow-up study.
AB  - This study reviews the clinical performance of 161 hip arthroplasties (154
      patients) with the Metasul metal-on-metal articulation and an uncemented modular
      acetabular component. Between 1995 and 2002 clinical evaluation and radiographic
      follow-up of patients included Harris hip scores, patient self-assessment, and
      radiographs. Twelve operative site complications (7.5%) included 6 revision
      operations, (3.7%) and 3 other complications (1.9%) not needing reoperation. Six
      revision operations (3.7%) included 1 femoral revision for aseptic loosening
      (0.06%) and 5 acetabular revisions (3.1%). One cup revision was for recurrent
      dislocation, 1 for disassociation of the acetabular insert from the cup, 1 for
      infection, and 2 for unexplained pain. Histologic evidence did not support the
      diagnosis of metal hypersensitivity in either case of unexplained pain, and 1 had
      relief following spine surgery. A focal radiolucency, identified as calcar
      resorption, was observed in 9 patients.

PMID- 15578550
TI  - Metal-on-metal bearings in cementless primary total hip arthroplasty.
AB  - One hundred cementless titanium primary total hip arthroplasties with 28 mm
      Metasul bearings were prospectively studied (osteoarthritis in 76% of hips, mean
      age 59.6 years). Ninety-eight were reviewed after a 6-year average follow-up
      (range, 17-126 months) with clinical results graded excellent and good in 97%.
      One femoral component was revised for aseptic loosening at 7.8 years.
      Postoperative cobalt level was higher than the upper "normal" value (5 microg/L
      in whole blood) for 16 cases. No significant relationship could be established
      between cobalt concentration increase and any demographic or surgical data,
      including activity level, except anteversion of the cup >25 degrees. In this
      early experience, impingement due to a head sleeve has been the main cause of
      dislocation and failure, and systemic cobalt survey appeared to be a good
      indicator of metal-on-metal bearing mechanical behavior.

PMID- 15578551
TI  - Large versus small femoral heads in metal-on-metal total hip arthroplasty.
AB  - The recent resurgence of metal-on-metal total hip arthroplasty has afforded the
      surgeon new options in femoral head diameters that were not previously available.
      Reduction in the risk for dislocation and potential improvements in articular
      wear are the obvious advantages of large-diameter femoral heads. Total hips with
      larger-diameter femoral heads are more resistant to dislocation. The clinical
      experience with 616 38 mm diameter femoral heads showed no dislocations within
      the first 3 months after surgery, compared with 2.5% of 78 patients receiving 28
      mm diameter femoral heads with otherwise identical components. Use of larger
      diameter femoral heads appears to have the potential to substantially reduce the
      early risk of dislocation of the prosthetic hip arthroplasty.

PMID- 15578552
TI  - Fixation strength of an all-metal acetabular component cemented into an
      acetabular shell: a biomechanical analysis.
AB  - When an acetabular shell is well fixed but the locking mechanism is compromised,
      cementing a new liner into the existing acetabular component can provide a simple
      revision solution. The pull-out and torsional fixation strength of cobalt
      chromium (CoCr) alloy acetabular components cemented into 3 sizes of titanium
      alloy acetabular components was tested under conditions of 0 or 2 mm cement
      mantle at the dome and 2 mm cement with the cemented component in 20 degrees of
      version with respect to the shell. The lowest mean tensile load to failure was
      1500 N, and occurred with no cement at the dome of the 54 mm shell, whereas the
      greatest load was with 2 mm cement thickness. Smallest mean torque to failure was
      43 Nm. Version angle did not substantially change failure load. Although not
      cyclically loaded, fixation strength of metal liners cemented into shells was
      comparable to that of commonly used locking mechanisms, suggesting sufficient
      strength for clinical application.

PMID- 15578553
TI  - How I choose a bearing surface for my patients.
AB  - There is insufficient clinical data to demonstrate the overall superiority of any
      one bearing couple for all total hip cases. It is therefore reasonable to
      individualize the choice of bearing surface. The fundamental exercise in choosing
      a bearing surface is maximizing the benefit to risk ratio. There are at least 3
      perspectives to consider: the patient's, the surgeon's, and that of the health
      care delivery system. The following question should be addressed on a patient-by
      patient basis: what available bearing is most likely to meet the needs of this
      patient, with an acceptable risk of revision surgery during his or her lifetime,
      is accepted in my community, and is there a means to pay for it?

PMID- 15578554
TI  - Surface arthroplasty for osteonecrosis of the hip: hemiresurfacing versus metal
      on-metal hybrid resurfacing.
AB  - Eighty-four hips with Ficat stage III and IV osteonecrosis were treated: 56 with
      metal-on-metal surface arthroplasty (MMSA) and 28 with hemi-surface arthroplasty
      (HSA). Average follow-up was 4.9 years. UCLA hip scores were significantly better
      for MMSA versus HSA for function and activity as well as Harris Hip scores and
      physical component of the SF-12 scores. In the MMSA group, 2 hips were revised to
      total hip arthroplasty for femoral loosening, and 5 hips had adverse radiological
      changes. In the HSA group, 4 hips were revised (1 sepsis and 3 for pain). There
      was no evidence of any femoral loosening or neck narrowing in the HSA group.
      Although the functional clinical outcome of MMSA is superior to HSA, long-term
      follow up of MMSA will determine the reliability of the femoral fixation.

PMID- 15578555
TI  - Can metal levels be used to monitor metal-on-metal hip arthroplasties?
AB  - In this review, the prospects for using blood, serum, and/or urine metal levels
      for monitoring the performance of metal-on-metal hip arthroplasty systems are
      explored. This approach does have substantial potential for serving this
      function; however, the methodology is technically challenging and the
      interpretation of the values requires an extensive database with correlative
      clinical information. At this time, it is premature to recommend metal
      concentration analysis on a routine clinical basis for patients with metal-on
      metal total hip arthroplasties. Nonetheless, metal concentration analysis remains
      a powerful research tool in the evaluation of metal-on-metal hip arthroplasty
      systems.

PMID- 15578556
TI  - Cup inclination and serum concentration of cobalt and chromium after metal-on
      metal total hip arthroplasty.
AB  - We investigated whether cup inclination influences serum levels of cobalt and
      chromium after metal-on-metal total hip arthroplasty. Out of a consecutive
      series, 3 groups of 20 patients each were established according to their cup
      inclination: greatest inclination (55 degrees -63 degrees, mean 58 degrees),
      intermediate inclination (44 degrees -46 degrees, mean 45 degrees), and smallest
      inclination (23 degrees -37 degrees, mean 33 degrees). We did not detect any
      statistically significant difference of serum cobalt (P = .23) or serum chromium
      (P = .13) levels between the 3 groups applying the Kruskal Wallis test. However,
      3 patients with cup inclinations of 58 degrees , 63 degrees , and 61 degrees
      exhibited 9.8-53.6-fold elevated cobalt and 9.5-30.5-fold elevated chromium
      levels when compared with the median concentrations of this trial. We therefore
      recommend accurate cup placement also for metal-on-metal articulations.

PMID- 15578557
TI  - Can a safe level for metal ions in patients with metal-on-metal total hip
      arthroplasties be determined?
AB  - The single most significant obstacle preventing a broader application of metal-on
      metal hip arthroplasties continues to be the concerns regarding elevated metal
      ion levels in the blood and urine of patients with this bearing. A safe level for
      metal ions has yet to be defined for patients with metal-on-metal hip
      arthroplasties. A review of occupational exposure data gives some insight;
      however, longitudinal studies of large numbers of patients with metal-on-metal
      implants will ultimately be required to answer specific clinical concerns.

PMID- 15578558
TI  - Changes in metal levels and chromosome aberrations in the peripheral blood of
      patients after metal-on-metal hip arthroplasty.
AB  - A prospective study was performed to investigate changes in metal levels and
      chromosome aberrations in patients within 2 years of receiving metal-on-metal hip
      arthroplasties. There was a statistically significant increase of cobalt and
      chromium concentrations, with a small increase in molybdenum, in whole blood at
      6, 12, and 24 months after surgery. There was also a statistically significant
      increase of both chromosome translocations and aneuploidy in peripheral blood
      lymphocytes at 6, 12, and 24 months after surgery. The changes were generally
      progressive with time, but the change in aneuploidy was much greater than in
      chromosome translocations. No statistically significant correlations were found
      in secondary analyses between chromosome translocation indices and cobalt or
      chromium concentration in whole blood. Although the clinical consequences of
      these changes, if any, are unknown, future epidemiological studies could usefully
      include direct comparisons of patients with implants of different composition.

PMID- 15578559
TI  - Induction of apoptosis and necrosis by metal ions in vitro.
AB  - There has been a renewed interest in the use of the metal-on-metal (MOM) implants
      for total hip arthroplasty (THA). It is well known, however, that the MOM
      articulation generates both metal particles and ions. The physiologic effects of
      these ions are poorly understood and their potential toxicity remains a cause for
      concern. In the present study, murine J774 macrophages were incubated with Co2+
      and Cr3+ ions and the mode of cell death (apoptosis/necrosis) was evaluated in
      vitro by transmission electron microscopy and cell death ELISA. Overall, results
      demonstrated that the mode of cell death was dependent on the ion concentration
      and the incubation time. Indeed, at short incubation times (24 h), the
      noninflammatory process of apoptosis was predominant. At longer incubation times
      (48 h), however, necrosis was predominant at higher ion concentrations.

PMID- 15578560
TI  - Immune responses correlate with serum-metal in metal-on-metal hip arthroplasty.
AB  - Cell-mediated hypersensitivity associated with metal components may be related to
      levels of implant debris. We tested this hypothesis by comparing lymphocyte
      reactivity to soluble Co, Cr, Ni, and Ti of patients with metal-on-polyethylene
      and metal-on-metal arthroplasties with healthy controls, and patients with
      osteoarthritis. The metal-on-metal group (n=9) demonstrated significantly
      elevated serum Co and Cr concentrations (13- and 58-fold, P<.05, respectively)
      and significantly elevated lymphocyte reactivity to Co (SI>5, P<.004) and Ni
      (SI>2.5, P<.01) when compared to controls (n=12) and subjects with metal-on-poly
      implants (n=7). These elevated in vivo metal levels demonstrated positive linear
      correlation with lymphocyte reactivity supporting our hypothesis that lymphocyte
      metal-induced reactivity increases with increased metal exposure. These results
      represent the first direct link between in vivo metal exposure and lymphocyte
      reactivity. Whether this lymphocyte reactivity to metal debris is etiologically
      linked to poor implant performance remains uncertain.

PMID- 15578561
TI  - Accumulation in liver and spleen of metal particles generated at nonbearing
      surfaces in hip arthroplasty.
AB  - Systemic migration of metal particles generated at nonbearing surfaces rather
      than the intended primary bearing was studied in postmortem specimens from 30
      patients with total hip arthroplasty. Using light and electron microscopy with x
      ray microanalysis, submicrometer metal particles were identified within
      macrophages in the liver and/or the spleen in 11 of 15 patients with a revised
      arthroplasty and in 2 of 15 patients with primary hip arthroplasty. The
      macrophages formed focal aggregates in the organs without apparent toxicity.
      Fretting at ancillary fixation devices, loose components, and modular connections
      can generate a substantial volume of debris. These particles are in addition to
      those generated at the bearing surfaces, further increasing both the local and
      systemic particulate burdens. While all components can be associated with the
      distant spread of particles and metal ions, it is the environment of revision
      arthroplasty that provides the greatest potential for the generation and systemic
      dissemination of wear debris. The long-term effects of accumulated wear particles
      in the liver and spleen are unknown.

PMID- 15578562
TI  - Does the placenta inhibit the passage of chromium and cobalt after metal-on-metal
      total hip arthroplasty?
AB  - Umbilical cord serum and corresponding maternal serum of 3 women with uncemented
      metal-on-metal total hip arthroplasties were analyzed for cobalt and chromium.
      The women were an average 3.8 (range, 2-5) years after hip surgery. At the time
      of delivery, the maternal chromium concentrations were 1.6 microg/l, 0.5
      microg/l, and 0.9 microg/l, respectively, and the maternal cobalt concentration
      was 1 microg/l in the first woman and below the detection limit in the other 2
      women. Cobalt and chromium concentrations of the 3 umbilical cord sera also were
      below the detection limit. This indicates that-with regard to the detection limit
      of our laboratory-we were unable to observe a passage of cobalt and chromium ions
      from metal-on-metal articulations across the placenta at the time of delivery.

PMID- 15578563
TI  - Effect of ion implantation on the tribology of metal-on-metal hip prostheses.
AB  - Nitrogen ion implantation (which considerably hardens the surface of the bearing)
      may represent one possible method of reducing the wear of metal-on-metal (MOM)
      hip bearings. Currently there are no ion-implanted MOM bearings used clinically.
      Therefore a physiological hip simulator test was undertaken using standard test
      conditions, and the results compared to previous studies using the same methods.
      N2-ion implantation of high carbon cast Co-Cr-Mo-on-Co-Cr-Mo hip prostheses
      increased wear by 2-fold during the aggressive running-in phase compared to
      untreated bearing surfaces, plus showing no wear reductions during steady-state
      conditions. Although 2 specimens were considered in the current study, it would
      appear that ion implantation has no clinical benefit for MOM.

PMID- 15578564
TI  - Comparative wear under different conditions of surface-engineered metal-on-metal
      bearings for total hip arthroplasty.
AB  - Metal-on-metal hip arthroplasties have demonstrated low wear rates. However, the
      ion release and toxicity of the metal wear particles remains a concern. Modifying
      the surface of metal bearings with thick chromium nitride (CrN) coatings has the
      potential to further reduce wear and ion release, and improve the
      biocompatibility of wear particles produced. The aim of this study was to
      investigate the application of surface engineering technology to modify metal-on
      metal (MOM) bearings to reduce wear and improve the functional biocompatibility
      of metal-on-metal prostheses. CrN-on-CrN bearings had lower wear rates in
      comparison to metal-on-metal bearings, particularly under adverse loading
      conditions. CrN-on-CrN bearings produced similar nanometer-sized particles to
      metal-on-metal bearings, however, CrN wear particles were less cytotoxic when
      cocultured with macrophage and fibroblast cells.

PMID- 15578565
TI  - A hip joint simulator study of the performance of metal-on-metal joints: Part I:
      the role of materials.
AB  - The use of metal-on-metal low-wearing bearings has promoted great interest in the
      factors determining the volume of wear debris generated in such joints, including
      the developing surface replacement alternatives. Twenty-six pairs of low- and
      high-carbon components in wrought or cast form of 36 mm nominal diameter and
      exhibiting similar clearances were studied over 5 million test cycles in a 10
      station hip joint simulator. Low-carbon cast materials exhibited higher wear than
      high-carbon cast or wrought materials. Little difference was found in the running
      in wear volumes generated by high-carbon wrought or cast materials, but the
      wrought material exhibited a slight advantage at the smallest diametral clearance
      considered of 105 microm. Volumetric wear appeared to decrease as the diametral
      clearance decreased.

PMID- 15578566
TI  - A hip joint simulator study of the performance of metal-on-metal joints: Part II:
      design.
AB  - The separate and combined roles of head diameter and clearance were studied
      experimentally in simulator tests and also theoretically. Head diameters ranging
      from 16-54 mm and various clearances were studied. Effective mixed-film
      lubrication achieved through careful design and manufacture greatly reduced wear.
      The running-in wear volumes were very low for larger-diameter heads and smaller
      clearances; but because the subsequent steady-state wear rate was much smaller
      than the running-in wear rate, the former contributed significantly to the total
      volume of wear debris even over very long periods of time. The design study has
      shown that head diameters should be as large as possible and diametral clearances
      as low as practicable, to ensure that the joints operate well into the mixed
      lubrication regime.

PMID- 15578567
TI  - EGF-stimulation activates the nuclear localization signal of SHP-1.
AB  - Protein tyrosine phosphatase SHP-1 plays a critical role in the regulation of a
      variety of intracellular signaling pathways. SHP-1 is predominantly expressed in
      the cells of hematopoietic origin, and is recognized as a negative regulator of
      lymphocyte development and activation. SHP-1 consists of two Src homology 2 (SH2)
      domains and one protein tyrosine phosphatase (PTP) domain followed by a highly
      basic C-terminal tail containing tyrosyl phosphorylation sites. It is unclear how
      the C-terminal tail regulates SHP-1 function. We report the examination of the
      subcellular localization of a variety of truncated or mutated SHP-1 proteins
      fused with enhanced green fluorescent protein (EGFP) protein at either the N
      terminal or the C-terminal end in different cell lines. Our data demonstrate that
      a nuclear localization signal (NLS) is located in the C-terminal tail of SHP-1
      and the signal is primarily defined by three amino-acid residues (KRK) at the C
      terminus. This signal is generally blocked in the native protein and can be
      exposed by fusing EGFP at the appropriate position or by domain truncation. We
      have also revealed that this NLS of SHP-1 is triggered by epidermal growth factor
      (EGF) stimulation and mediates translocation of SHP-1 from the cytosol to the
      nucleus in COS7 cell lines. These results not only demonstrate the importance of
      the C-terminal tail of SHP-1 in the regulation of nuclear localization, but also
      provide insights into its role in SHP-1-involved signal transduction pathways.

PMID- 15578568
TI  - Effect of CD44 deficiency on in vitro and in vivo osteoclast formation.
AB  - In vitro studies have shown that CD44 is involved in the fusion process of
      osteoclast precursor cells. Yet, in vivo studies do not support this, since an
      osteopetrotic phenotype has not been described for CD44 knock-out (CD44 k.o.)
      mice. This discrepancy may suggest that the role of CD44 in fusion may depend on
      the microenvironment of osteoclast formation. We investigated osteoclast
      formation of CD44 k.o. and wild-type mice under three conditions: in vitro, both
      on plastic and on bone and in vivo by analyzing osteoclast number, and size in
      long bones from wild-type and CD44 k.o. mice. Bone marrow cells from wild-type
      and CD44 k.o. mice were analyzed for their capacity to form osteoclasts on
      plastic and on bone in the presence of macrophage colony stimulating factor (M
      CSF) and receptor activator of NF-kB ligand (RANKL). On plastic, the number of
      multinucleated tartrate resistant acid phosphatase (TRAP) positive cells in CD44
      k.o. cultures was twofold higher than in wild-type cultures. On bone, however,
      equal numbers of osteoclasts were formed. Interestingly, the total number of
      osteoclasts formed on bone proved to be higher than on plastic for both
      genotypes, strongly suggesting that osteoclastogenesis was stimulated by the bone
      surface, and that CD44 is not required for osteoclast formation on bone.
      Functional analyses showed that bone resorption was similar for both genotypes.
      We further studied the osteoclastogenic potential of wild-type bone marrow cells
      in the presence of CD44 blocking antibodies. Osteoclastogenesis was not affected
      by these antibodies, a further indication that CD44 is not required for the
      formation of multinucleated cells. Finally, we analyzed the in vivo formation of
      osteoclasts by analyzing long bones from wild-type and CD44 k.o. mice.
      Morphometric analysis revealed no difference in osteoclast number, nor in number
      of nuclei per osteoclasts or in osteoclast size. Our in vitro experiments on
      plastic showed an enhanced formation of osteoclasts in the absence of CD44, thus
      suggesting that CD44 has an inhibitory effect on osteoclastogenesis. However,
      when osteoclasts were generated on bone, no differences in number of
      multinucleated cells nor in bone resorption were seen. These observations are in
      agreement with in vivo osteoclast characteristics, where no differences between
      wild-type and CD44 k.o. bones were encountered. Therefore, the modulating role of
      CD44 in osteoclast formation appears to depend on the microenvironment.

PMID- 15578569
TI  - T-cell factor-4-dependent up-regulation of fibronectin is involved in fibroblast
      growth factor-2-induced tube formation by endothelial cells.
AB  - Deletion of fibronectin or its receptor, alpha(5) integrin, interferes with the
      formation of a functional circulation in mice. We hypothesized that
      alpha(5)beta(1) integrin/fibronectin interaction may be involved in
      differentiation of endothelial cells during angiogenesis. We examined the effect
      of blocking antibody against alpha(5)beta(1) integrin in fibroblast growth factor
      2 (FGF-2)-induced angiogenesis by Matrigel plug assay. Although the antibody did
      not inhibit the recruitment of endothelial cells into plugs, it inhibited
      organization of lumen-containing capillaries. The antibody also inhibited FGF-2
      induced tube formation by murine brain capillary endothelial cells (IBE cells)
      cultured in type I collagen gels. We previously showed that FGF-2 failed to
      induce tube formation by IBE cells expressing kinase-dead c-Fyn (KDFyn cells).
      Association with beta-catenin enhances the transcriptional activity of T-cell
      factor-4 (TCF-4), which up-regulates the expression of fibronectin. FGF-2 induced
      association of beta-catenin with TCF-4 and up-regulation of fibronectin in IBE
      cells, but not in KDFyn cells. Expression of mutant TCF-4, which does not
      associate with beta-catenin, inhibited FGF-2-induced tube formation and
      expression of fibronectin in IBE cells. FGF-2-induced tyrosine phosphorylation of
      beta-catenin, and association with TCF-4 was increased in IBE cells, but not in
      KDFyn cells. Taken together, interaction of alpha(5)beta(1) integrin and
      fibronectin is involved in FGF-2-induced tube formation by endothelial cells and
      up-regulation of fibronectin through TCF-4 seemed to be involved in this process.

PMID- 15578570
TI  - Head structures of males of Strepsiptera (Hexapoda) with emphasis on basal
      splitting events within the order.
AB  - Internal and external head structures of males of Strepsiptera were examined and
      the head of a species of Mengenilla is described in detail. The results suggest a
      reinterpretation of some structures. The head of basal extant strepsipterans is
      subprognathous, whereas it is strictly orthognathous in the groundplan of
      Strepsiptera s.l. The labrum and hypopharynx are not part of the mouthfield
      sclerite. The labial palps are absent in all strepsipterans. A very slightly
      modified mandibular articulation is preserved in Eoxenos, whereas it is
      distinctly reduced in other extant groups. A salivary duct, salivary glands, and
      a cephalic aorta are absent. The cladistic analysis of 44 characters of the head
      results in the following branching pattern: (Protoxenos + (Mengea + (Eoxenos +
      (Mengenilla [Austr.] + Mengenilla) + (Elenchus + Dundoxenos + Xenos +
      Stylops)))). Most apomorphies of males are associated with the necessity of
      finding females within a short time span and with a reduced necessity to consume
      food: large "raspberry" eyes, flabellate antennae with numerous dome-shaped
      chemoreceptors, Hofeneder's organ, an ovoid sensillum of the maxillary palp, and
      the simplified condition of the maxilla and the labium. Strepsiptera excl.
      Protoxenos are supported by the dorsomedian frontal impression, the dorsally
      shifted antennal insertions, a reduced number of antennal segments, absence of
      the galea, and probably by the presence of the mouthfield sclerite, which is a
      unique apomorphic feature. The balloon-gut combined with an unusual air-uptake
      apparatus is another possible autapomorphy of this clade. It is likely that the
      last common ancestor of Strepsiptera excl. Protoxenos did not process food.
      Strepsiptera s.str. are characterized by the strongly reduced condition of the
      labrum and the absence of the epistomal suture. Eoxenos is the sister group of
      the remaining Strepsiptera s.str. Synapomorphies of Mengenilla + Stylopidia are
      the advanced reduction of the mandibular articulation and the secondary absence
      of the ovoid sensillum. The monophyly of Mengenilla is confirmed, even though a
      small free labrum is present in Australian species. Derived features of
      Stylopidia are the absence of the coronal suture and the reduced condition of the
      frontal suture. Apomorphies that have evolved within Stylopidia are the
      membranization of parts of the head, the fusion of antennal segments, the
      increase or decrease of the number of flabellate flagellomeres, reductions and
      modifications of the mandibles, and modifications of the mouthfield sclerite. The
      monophyly of Stylopiformia is not unambiguously supported. A position of the
      mandibles posterior to the mouthfield sclerite (when adducted) is a possible
      synapomorphy shared by Xenos, Stylops, and other "higher Stylopidia." The blade
      like distal part of the mandibles suggests a closer relationship of Elenchus with
      these taxa.

PMID- 15578571
TI  - Regulation of naturally occurring antisense RNA of myosin heavy chain (MyHC) in
      neonatal cardiomyocytes.
AB  - Naturally occurring antisense RNA has been detected for a range of eukaryotic
      genes. Its abundance compared to levels of its complementary sense mRNA appears
      to be a factor indicating its possible regulatory function. In previous studies,
      we detected appreciable levels of antisense RNA against the two isoforms (alpha
      and beta) of the heavy myosin-chain (MyHC) in the myocardium of rats. If this is
      to play a significant role in gene expression antisense levels should vary in
      response to external and internal cellular influences. Recently, a bidirectional
      promoter located in the alpha/beta MyHC intergenic region was described, which
      was proposed to regulate coordinated transcription of alpha-MyHC sense and beta
      MyHC antisense. To study MyHC antisense regulation in neonatal heart, we
      investigated cultivated myocytes stimulated with either trijodthyronin (T3) as an
      inductor of alpha-MyHC or phenylephrine with stimulation of beta-MyHC. RNA
      quantification of sense and antisense transcripts of both isoforms was performed
      by real-time RT-PCR. Stimulation by T3 led to an induction of both sense and
      antisense of alpha-MyHC and to a decrease of beta-MyHC sense and antisense.
      Phenylephrine increased sense and antisense beta-MyHC but reduced antisense alpha
      MyHC. The sense/antisense of alpha- and beta-MyHC ratio was unchanged compared to
      control. Results indicate a coregulation of sense and antisense MyHC RNA under
      stimulation of T3 and phenylephrine in neonatal cardiomyocytes.

PMID- 15578572
TI  - The real earliest historical evidence of Down syndrome.

PMID- 15578573
TI  - Aplasia cutis congenita, skull defect, brain heterotopia, and intestinal
      lymphangiectasia.
AB  - We describe a female infant with a previously unreported combination of
      manifestations characterized by aplasia cutis, skull defect, brain heterotopia,
      mild congenital lymphedema, and intestinal lymphangiectasia. The association of
      intestinal lymphangiectasia and aplasia cutis, and the association of intestinal
      lymphangiectasia with brain heterotopia in the lymphedema-lymphangiectasia-mental
      retardation syndrome have been described in single reports. In one family, the
      association of cortical dysplasia and congenital lymphedema have been related to
      mutations in the RELN gene.

PMID- 15578574
TI  - Regucalcin stimulates osteoclast-like cell formation in mouse marrow cultures.
AB  - The effect of regucalcin, a regulatory protein in intracellular signaling, on
      osteoclastic cell formation in mouse bone marrow culture is investigated. The
      bone marrow cells were cultured for 7 days in an alpha-minimal essential medium
      containing either vehicle or regucalcin (10(-10)-10(-8)M). Osteoclast-like cell
      formation was estimated by staining for tartrate-resistant acid phosphatase
      (TRACP), a marker enzyme of osteoclasts. The presence of regucalcin (10(-10)-10(
      8)M) caused a remarkable increase in osteoclast-like multinucleated cells (MNCs).
      The effect of regucalcin in stimulating osteoclast-like cell formation was
      significantly inhibited in the presence of calcitonin (CT; 10(-9)M), 17beta
      estradiol (10(-9)M), beta-cryptoxanthin (CX; 10(-6)M), or zinc sulfate (10(-4)M),
      which is an anti-bone resorbing factor. The effect of regucalcin on osteoclast
      like cell formation was not significantly blocked in the presence of
      cycloheximide, an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB), an inhibitor of transcriptional activity. The
      effect of parathyroid hormone (10(-7)M), 1,25-dihydroxyvitamin D(3) (10(-7)M),
      prostaglandin E(2) (10(-5)M), or tumor necrosis factor-alpha (10 ng/ml) in
      increasing osteoclast-like cell formation was significantly enhanced in the
      presence of regucalcin (10(-8)M). Moreover, when rat femoral-diaphyseal or 
      metaphyseal tissues were cultured for 48 h in the presence of regucalcin (10(-10)
      10(-8)M), the diaphyseal or metaphyseal calcium content was significantly
      decreased in the presence of regucalcin (10(-10)-10(-8)M) in vitro. The
      consumption of glucose and the production of lactic acid in culture medium by the
      diaphyseal or metaphyseal tissues was significantly raised in the presence of
      regucalcin (10(-10)-10(-8)M). This study demonstrates that regucalcin directly
      stimulates osteoclast-like cell formation in mouse marrow culture in vitro, and
      that the protein stimulates bone resorption in rat femoral tissues in vitro.

PMID- 15578575
TI  - Sensing, signaling, and responding to DNA damage: organization of the checkpoint
      pathways in mammalian cells.
AB  - The DNA damage and replication checkpoints are signaling mechanisms that regulate
      and coordinate cellular responses to genotoxic conditions. Unlike typical signal
      transduction mechanisms that respond to one or a few stimuli, checkpoints can be
      activated by a broad spectrum of extrinsically or intrinsically derived DNA
      damage or replication interference. Recent investigations have shed light on how
      the damage and replication checkpoints are able to respond to such diverse
      stimuli. The activation of checkpoints not only attenuates cell cycle progression
      but also facilitates DNA repair and recovery of faltered replication forks,
      thereby preventing DNA lesions from being converted to inheritable mutations.
      Recently, more checkpoint targets from the cell cycle and DNA replication
      apparatus have been identified, revealing the increasing complexity of the
      checkpoint control of the cell cycle. In this article, we discuss current models
      of the DNA damage and replication checkpoints and highlight recent advances in
      the field.

PMID- 15578576
TI  - Rett syndrome in females with CTS hot spot deletions: a disorder profile.
AB  - From a series of 107 females with Rett syndrome (RTT), we describe the long-term
      history of ten females with a deletion in the C-terminus of the MECP2 gene. We
      observed that their disorder profile is clinically recognizable with time and
      different from other atypical and milder RTT phenotypes. In females with hot spot
      deletions in the C-terminus, dystonia is present from childhood and results in a
      serious spine deformation in spite of preventive measures. Their adaptive
      behavior is surprisingly better preserved and in contrast with the typical
      decline in motor functioning. The delineation of disorder profiles by long-term
      clinical observation can teach us about genotype/phenotype relationships and
      eventually about the effect of epigenetic phenomena on the final phenotype.

PMID- 15578577
TI  - Unique survival in chrondrodysplasia-hermaphrodism syndrome.

PMID- 15578578
TI  - Differentiation of HL-60 cells to granulocytes involves regulation of select
      diacylglycerol kinases (DGKs).
AB  - Diacylglycerol Kinases (DGKs) are a family of enzymes that regulate the levels of
      different pools of diacylglycerol (DAG), affecting DAG-mediated signal
      transduction. Since DAG is known to play several important regulatory roles in
      granulocyte physiology, we investigated the expression pattern of DGK isoforms
      throughout differentiation of HL-60 cells to granulocytes. HL-60 cells were
      incubated with 1.25% dimethyl-sulfoxide (DMSO) to initiate differentiation and
      total RNA isolated at different time points. DGK expression was assessed through
      Northern blot, end-point PCR, and real-time PCR. The non-selective inhibitors
      R59022 and R59949 were used to block DGK at different time points throughout
      differentiation. CD11b and GPI-80, reactive oxygen species (ROS) generation,
      changes in the cell cycle, and apoptosis were used as markers of differentiation.
      Of the nine isoforms of DGK evaluated (alpha, delta, epsilon, gamma, zeta, beta,
      theta;, iota, eta), only five (alpha, delta, epsilon, gamma, and zeta) were
      expressed in HL-60 cells. DGKalpha was virtually absent in non-differentiated
      cells, but was markedly upregulated throughout differentiation. The other
      isoforms (delta, epsilon, gamma, and zeta) were expressed in undifferentiated HL
      60 cells but were substantially decreased throughout differentiation. Non
      selective blocking of DGK with R59022 and R59949 led to acceleration of
      differentiation, reducing the time necessary to observe upregulation of CD11b,
      GPI-80 and generation of ROS by 50%. Likewise, the cell cycle was disrupted when
      DGK isoforms were inhibited. These results provide evidence that DGK levels are
      dynamically regulated throughout differentiation and that expression of DGKs play
      an important regulatory function during the differentiation of neutrophils.

PMID- 15578579
TI  - Pfeiffer type cardiocranial syndrome and van Nesselrooij syndrome--variable
      manifestations of a single disorder?

PMID- 15578580
TI  - Functional domains of necdin for protein-protein interaction, nuclear matrix
      targeting, and cell growth suppression.
AB  - Necdin is a growth suppressor expressed predominantly in postmitotic neurons. The
      necdin gene is involved in the etiology of the genomic imprinting-associated
      neurodevelopmental disorder Prader-Willi syndrome and belongs to the MAGE gene
      family. All the MAGE family proteins contain a large homology domain termed the
      MAGE homology domain (MHD). We here characterize the regions of necdin required
      for the protein-protein interaction, nuclear matrix targeting, and cell growth
      suppression. The region including entire MHD (amino acids 116-280) of necdin was
      required for its interaction with p53, while the regions amino acids 144-184 and
      191-222 within the MHD were required for both the nuclear matrix targeting and
      the cell growth suppression of osteosarcoma SAOS-2 cells. The amino-terminal
      proline-rich acidic region (amino acids 60-100) was also necessary for cell
      growth suppression. Tetracycline-regulatable overexpression of necdin induced
      growth arrest of SAOS-2 cells in a reversible manner, and the necdin
      overexpressing cells showed a large, flattened morphology with double nuclei. In
      contrast, a necdin mutant lacking amino acids 191-222 did not induce such
      changes. These findings suggest that different functions of necdin are mediated
      via its distinct domains.

PMID- 15578581
TI  - MECP2 mutation analysis in patients with mental retardation.
AB  - Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are known to underlie
      Rett' syndrome, the most common cause of mental retardation (MR) in girls. Since
      the original report, phenotypes resulting from MECP2 mutations have been shown to
      extend, for example, to several Rett variants, autism, atypical Angelman
      syndrome, and nonspecific MR. It was earlier proposed that MECP2 mutations might
      account for approximately 2% of the male cases with nonspecific MR. Thereby, the
      frequency of MECP2 mutations in the mentally retarded population would be
      comparable to that of Fragile-X syndrome. The aim of this study was to analyze
      well-characterized cases with MR and to clarify the role of the MECP2 gene in the
      etiology of MR and atypical Angelman syndrome. The coding sequence of the MECP2
      gene was analyzed in a sample of 118 patients (103 males, 15 females) by direct
      sequencing. Two coding sequence variants, 602C > T (A201V) and 1189G > A (E397K),
      were identified. In addition, we identified four variants in the intronic or
      3'UTR regions. None of these variants is likely to be causal. We conclude that
      the evidence across all the mutation screening studies implies that MECP2
      mutations do not represent a major cause of nonspecific MR.

PMID- 15578582
TI  - Hand involvement in Schmid metaphyseal chondrodysplasia.
AB  - Schmid metaphyseal chondrodysplasia (Schmid MCD, MIM 156500) is caused by
      mutations in the COL10A1 gene and is clinically characterized by short stature,
      bowed legs, and a waddling gait. Radiographic findings include anterior cupping,
      sclerosis and splaying of the ribs, diffuse metaphyseal flaring, and irregularity
      that is most pronounced at the knees, coxa vara, and femoral bowing. We reviewed
      the radiographs of Schmid MCD patients at the International Skeletal Dysplasia
      Registry in Los Angeles for evidence of hand involvement. We found hand
      involvement in 47% (7/15) of cases included in our analysis. These changes were
      subtle and consisted of shortening of the tubular bones and metaphyseal cupping
      of the proximal phalanges and metacarpals. Mild hand involvement is a common
      feature of Schmid MCD.

PMID- 15578583
TI  - Additional case of Tsukahara's syndrome or new syndrome: further delineation of
      the association of microcephaly and radio-ulnar synostosis.
AB  - In 1994, Giuffre et al. reported two unrelated families in which some of the
      members had microcephaly and radio-ulnar synostosis, suggesting a new condition.
      Since this first report, Tsukahara et al. and Udler et al. described two distinct
      patients with a different condition characterized by radio-ulnar synostosis,
      short stature, microcephaly, scoliosis, and mental retardation. Here we report on
      a new case of microcephaly and radio-ulnar synostosis and discuss the possible
      relationship between Tsukahara's syndrome and the phenotype described by Giuffre
      et al.

PMID- 15578584
TI  - Association of anophthalmia and esophageal atresia: four new cases identified by
      the anophthalmia/microphthalmia clinical registry.
AB  - We report four new cases of the rare association of anophthalmia and esophageal
      atresia. There are only nine cases previously reported in the literature with
      this association. Our cases appear to be distinct from those already reported,
      thus increasing the number of cases to thirteen. Advances in developmental
      biology have shown that mutations in developmental genes active early in
      embryogenesis can lead to birth defects in multiple, seemingly unrelated systems.
      The network of genes that directs development has been highly conserved through
      evolution. Several transcription factors have been shown to be important in
      regulating eye development. Mutations in these developmental genes may be the
      cause of this clinical association.

PMID- 15578585
TI  - The mildest form of campomelic dysplasia.

PMID- 15578586
TI  - Activation of protein phosphatase-2A1 by HIV-1 Vpr cell death causing peptide in
      intact CD(4+) T cells and in vitro.
AB  - HIV-1, the etiologic agent of human AIDS, causes cell death in host and non-host
      cells via HIV-1 Vpr, one of its auxiliary gene product. HIV-1 Vpr can also cause
      cell cycle arrest in several cell types. The cellular processes that link HIV-1
      Vpr to the cell death machinery are not well characterized. Here, we show that
      the C terminal portion of HIV-1 Vpr which encompasses amino acid residues 71-96
      (HIV-1 Vpr(71-96)), also termed HIV-1 Vpr cell death causing peptide, is an
      activator of protein phosphatase-2A(1) when applied extracellularly to CD(4+) T
      cells. HIV-1 Vpr(71-96) is a direct activator of protein phosphatase-2A(1) that
      has been purified from CD(4+) T cells. Full length HIV-1 Vpr by itself does not
      cause the activation of protein phosphatase-2A(1) in vitro. HIV-1 Vpr(71-96) also
      causes the activation of protein phosphatase-2A(0) and protein phosphatase-2A(1)
      from brain, liver, and adipose tissues. These results indicate that HIV-1 can
      cause cell death of infected cells and non-infected host and non-host cells via
      HIV-1 Vpr derived C terminal peptide(s) which act(s) by cell penetration and
      targeting of a key controller of the cell death machinery, namely, protein
      phosphatase-2A(1). The activation of other members of the protein phosphatase-2A
      subfamily of enzymes which are involved in the control of several metabolic
      pathways in brain, liver, and adipose tissues by HIV-1 Vpr derived C terminal
      peptide(s) may underlie various metabolic disturbances that are associated with
      HIV-1 infection.

PMID- 15578587
TI  - Molecular and cytogenetic characterization of a non-mosaic isodicentric Y
      chromosome in a patient with Klinefelter syndrome.
AB  - We report on an adult male with Klinefelter phenotype and an isodicentric Y
      chromosome (47,XX,+idic(Y)(q12)), a combination which has to the best of our
      knowledge not been reported before. The patient was hospitalized in forensic
      psychiatry because of repeated delinquency, aggressive, aberrant and
      inappropriate behavior, and borderline intelligence. Molecular cytogenetic
      studies (FISH) showed that the SRY gene was present on both ends of the idicY,
      while there was only one signal for the Yq subtelomere probe. Molecular
      investigations by multiplex PCR, using STS markers covering the short and long
      arm of the Y chromosome did not indicate a deletion of Y chromosomal material.
      Molecular investigations of STR markers located on Xp22.3 and Xq28 indicated
      paternal origin of the additional X chromosome and an error in paternal meiosis
      I. Results of FISH analysis and molecular investigations are compatible with a
      phenotype as described for individuals with a 48,XXYY karyotype and support the
      findings that isodicentric Y chromosomes are frequently accompanied by other sex
      chromosomal abnormalities.

PMID- 15578588
TI  - Thermotolerance of pulp cells and phagocytosis of apoptotic pulp cells by
      surviving pulp cells following heat stress.
AB  - Apoptosis is known to be associated with wound healing and regeneration of dental
      pulp. We examined the effects of heat stress on clonal dental pulp cell line (RPC
      C2A cells) to clarify the pulp wound healing process. RPC-C2A cells were exposed
      to heat stress at 43 degrees C for 45 min. After several time intervals, the
      inhibition of cell proliferation and apoptosis induction were analyzed by cell
      viability assay, DNA gel electrophoresis, nuclear staining, and terminal
      deoxynucleotidyl transferase mediated labeling assay. RPC-C2A cells showed the
      thermotolerance following heat stress. We found that apoptosis was induced in
      some RPC-C2A cells, whereas others remained alive, and observed the engulfment of
      apoptotic cells by scavenger-like RPC-C2A cells following heat stress. We also
      analyzed the phagocytotic activity of RPC-C2A cells and found that they had an
      ability to engulf apoptotic RPC-C2A cells, which was stimulated by heat stress.
      These results suggest that heat stress induces apoptosis of RPC-C2A cells, which
      are phagocytosed by the surviving RPC-C2A cells.

PMID- 15578589
TI  - Behavioral aspects of Angelman syndrome: a case control study.
AB  - Angelman syndrome (AS) is a rare congenital disorder characterized by impairments
      in intellectual, neurological and motor functioning and a postulated behavioral
      profile. This study compared behavioral characteristics of 62 individuals with
      genetically confirmed AS and 29 individuals with presumed AS from clinical
      features, with a control group of young persons with intellectual disability (ID)
      derived from an Australian epidemiological register. Twelve behavioral items from
      the developmental behavior checklist (DBC) were used for this comparison. The
      groups were matched for chronological age, gender, and level of ID. In the AS
      group, significant differences were found for 10 behaviors, with poor attention
      span and impulsivity being less common, and overactivity/restlessness, chewing or
      mouthing objects, eating non-food items, gorging food, food fads, fascination for
      water, hand flapping and sleep disturbance being more common. Interestingly,
      there was no difference in prevalence of unprovoked laughter. Comparison of the
      results of the genetically confirmed with the genetically unconfirmed AS cases
      showed no significant differences between individual behavior prevalence. These
      findings show that a "behavioral phenotype" of AS can be distinguished from
      others of similar level of ID, but it is different from that hitherto published.
      Abnormal food related behaviors, hyperactivity, fascination for water, hand
      flapping, and sleep disturbance should be included in a "behavioral phenotype"
      for AS. Apart from hyperactivity, "ADHD-type" behaviors are not more
      characteristic of AS than in ID generally. Therefore, the Consensus Criteria for
      the diagnosis of AS need to be reviewed.

PMID- 15578590
TI  - Molecular and functional comparison of 1,25-dihydroxyvitamin D(3) and the novel
      vitamin D receptor ligand, lithocholic acid, in activating transcription of
      cytochrome P450 3A4.
AB  - The vitamin D receptor (VDR) binds to and mediates the effects of the 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) hormone to alter gene transcription. A
      newly recognized VDR ligand is the carcinogenic bile acid, lithocholic acid
      (LCA). We demonstrate that, in HT-29 colon cancer cells, both LCA and
      1,25(OH)(2)D(3) induce expression of cytochrome P450 3A4 (CYP3A4), an enzyme
      involved in cellular detoxification. We also show that LCA-VDR stimulates
      transcription of gene reporter constructs containing DR3 and ER6 vitamin D
      responsive elements (VDREs) from the human CYP3A4 gene. Utilizing gel mobility
      shift, pulldown, and mammalian two-hybrid assays, we observe that: (i)
      1,25(OH)(2)D(3) enhances retinoid X receptor (RXR) heterodimerization with VDR
      more effectively than LCA, (ii) the 1,25(OH)(2)D(3)-liganded VDR-RXR heterodimer
      recruits full-length SRC-1 coactivator, whereas this interaction is minimal with
      LCA unless LXXLL-containing fragments of SRC-1 are employed, and (iii) both
      1,25(OH)(2)D(3) and LCA enhance the binding of VDR to DRIP205/mediator, but
      unlike 1,25(OH)(2)D(3)-VDR, LCA-VDR does not interact detectably with NCoA-62 or
      TRIP1/SUG1, suggesting a different pattern of LCA-VDR comodulator association.
      Finally, residues in the human VDR (hVDR) ligand binding domain (LBD) were
      altered to create mutants unresponsive to 1,25(OH)(2)D(3)- and/or LCA-stimulated
      transactivation, identifying S237 and S225/S278 as critical for 1,25(OH)(2)D(3)
      and LCA action, respectively. Therefore, these two VDR ligands contact distinct
      residues in the binding pocket, perhaps generating unique receptor conformations
      that determine the degree of RXR and comodulator binding. We propose that VDR is
      a bifunctional regulator, with the 1,25(OH)(2)D(3)-liganded conformation
      facilitating high affinity endocrine actions, and the LCA-liganded configuration
      mediating local, lower affinity cellular detoxification by upregulation of CYP3A4
      in the colon.

PMID- 15578591
TI  - Interval estimation and hypothesis testing of intraclass correlation
      coefficients: the generalized variable approach.
AB  - In this paper, we propose a novel approach using the concept of generalized
      variable (GV) for the confidence interval estimation of the difference of two
      intraclass correlation coefficients under unequal family sizes. This approach can
      also easily provide P-values for hypothesis testing. Simulation results show that
      the GV approach can provide confidence intervals with good coverage properties
      and perform hypothesis testing with satisfactory type-I error control.
      Furthermore, the confidence intervals and P-values by GV approach can be easily
      obtained by simulation. Therefore the GV approach is a suitable candidate for
      making inference concerning two intraclass correlation coefficients.

PMID- 15578592
TI  - The 3111T/C polymorphism of hClock is associated with evening preference and
      delayed sleep timing in a Japanese population sample.
AB  - Sleep timing is influenced by the circadian system. Morningness-eveningness (ME)
      preference in humans is affected by the free-running period, which is determined
      by circadian clock-relevant genes. In this study, we investigated association
      between the 3111T/C polymorphism in the 3'-flanking region of hClock (Homo
      sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne
      Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score
      of 51.2 +/- 1.4 (range, 25-73), and scores were positively correlated with sleep
      onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ
      scores were significantly lower in subjects with 3111C/C (n = 12) than in
      subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001),
      suggesting a stronger eveningness preference in 3111C/C homozygotes. This group
      also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P
      < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters
      in the subjects with the 3111T allele. There was no significant difference in any
      of these parameters between the 3111C/T and 3111T/T genotypes. The influence of
      the 3111T/C polymorphism on ME preferences in Caucasian populations remains
      controversial. The present findings in a Japanese population sample, which should
      have a relatively low risk of population stratification effects, suggest the
      significance of the association of the 3111C/C allele of hClock with evening
      preference.

PMID- 15578593
TI  - Application of residual dipolar couplings in organic compounds.
AB  - Residual dipolar couplings (RDCs) induced by anisotropic media are a powerful
      tool for the structure determination of biomolecules through NMR spectroscopy.
      Recent advances have proven it to be a valuable tool for determination of the
      stereochemistry of organic molecules. By simple inspection or order matrix
      calculations, RDCs provide unambiguous information about the relative
      configurations or complete stereochemistry of organic compounds.

PMID- 15578595
TI  - Identification of the Rdl mutation in laboratory and field strains of the cat
      flea, Ctenocephalides felis (Siphonaptera: Pulicidae).
AB  - In many insect species, resistance to cyclodiene insecticides is caused by amino
      acid substitutions at a single residue (A302) within the M2 transmembrane region
      of the gamma-aminobutyric acid (GABA) receptor sub-unit termed Rdl (resistance to
      dieldrin). These mutations (A302S and A302G) have also been shown to confer
      varying levels of cross-resistance to fipronil, a phenylpyrazole insecticide with
      a similar mode of action to cyclodienes. To investigate the possible occurrence
      of these mutations in the cat flea, Ctenocephalides felis (Bouche), a 176-bp
      fragment of the cat flea Rdl gene, encompassing the mutation site, was PCR
      amplified and sequenced from nine laboratory flea strains. The A302S mutation was
      found in eight of the nine strains analysed, although the relative frequency of
      the mutant allele varied between strains. Only one strain (R6) was found to be
      homozygous for the S302 allele in all the individuals tested, and this correlated
      with previous reports of low-level fipronil resistance in this strain. A PCR
      based diagnostic assay, capable of screening individual fleas for this mutation,
      was developed and used to survey a range of fleas collected at random from
      veterinary clinics in the UK and USA. The A302S mutation was present at a high
      frequency in these domestic pet populations.

PMID- 15578596
TI  - Evidence for occurrence of an organophosphate-resistant type of
      acetylcholinesterase in strains of sea lice (Lepeophtheirus salmonis Kroyer).
AB  - Acetylcholinesterase (AChE) is the target of a major pesticide family, the
      organophosphates, which were extensively used as control agents of sea lice on
      farmed salmonids in the early 1990s. From the mid-1990s the organophosphates
      dichlorvos and azamethiphos were seriously compromised by the development of
      resistance. AChE insensitive to organophosphate chemotherapeutants has been
      identified as a major resistance mechanism in numerous arthropod species, and in
      this study, target-site resistance was confirmed in the crustacean Lepeophtheirus
      salmonis Kroyer isolated from several fish-farming areas in Norway and Canada. A
      bimolecular rate assay demonstrated the presence of two AChE enzymes with
      different sensitivities towards azamethiphos, one that was rapidly inactivated
      and one that was very slowly inactivated. To our knowledge this is the first
      report of target-site resistance towards organophosphates in a third class of
      arthropods, the Crustacea.

PMID- 15578597
TI  - The behavioural response of slugs and snails to novel molluscicides, irritants
      and repellents.
AB  - The behavioural response of the slug Deroceras panormitanum (Lessona and
      Pollonera) and the snail Oxyloma pfeifferi (Rossmassler) to novel molluscicides
      was investigated in choice and no-choice experiments. Low-light video-recording
      in combination with automated tracking and event recording was used to identify
      the repellent and irritant effects of (1) cinnamamide, (2) copper ammonium
      carbonate, (3) a mulch, (4) a horticultural ground-cover matting impregnated with
      a copper formulation and (5) urea/formaldehyde. In the no-choice experiments the
      products had a stronger irritant effect on the snails than on the slugs. All
      products tested except the mulch significantly reduced the locomotor activity of
      both the slugs and snails. The most effective product, cinnamamide, reduced snail
      locomotor activity by 94% and track length by 96%. The overall repellent effect
      of the treatments in the choice experiments was stronger in the slugs; where
      presence, locomotor activity and track length in the treated area were
      significantly reduced by all products. The avoidance of treated areas exceeded
      95% with the mulch (for slugs) and with copper ammonium carbonate (for snails).

PMID- 15578598
TI  - Synthesis and herbicidal activity of novel heterocyclic protoporphyrinogen
      oxidase inhibitors.
AB  - Protox inhibitors are applied as foliar sprays, thus causing very rapid cellular
      collapse and desiccation of many troublesome weeds in the presence of light. In
      many respects, they appear to be ideal herbicides, because they act rapidly and
      do not harm mammals under normal conditions. The main limitation to their
      widespread adoption is that few crops are naturally resistant to them. Crop
      tolerance has mainly been pursued with the synthesis of the cyclic imide classes
      containing 5- and 6-membered heterocycles, including pyrazole, pyridazine, 1,2,4
      triazine, triazolinone and trifluoromethyluracil derivatives. Because of their
      structural novelties and biological performance, active investigations on
      heterocyclic protox inhibitors have been carried out in our laboratories and we
      have found 3-arylpyrroles to be a new class of light-activated, membrane
      disrupting herbicides. They are active on both grass and broadleaf weeds at low
      rates. The synthesis and structure-activity relationships are presented.

PMID- 15578599
TI  - Activity of gut proteinases from Cry1Ab-selected colonies of the European corn
      borer, Ostrinia nubilalis (Lepidoptera: Crambidae).
AB  - Susceptibility to the Cry1Ab protoxin and toxin from Bacillus thuringiensis
      (Berliner) and activity of gut proteinases were assessed in both susceptible and
      Cry1Ab-selected colonies of European corn borer, Ostrinia nubilalis (Hubner).
      Resistance in two different selected colonies was at least 6- and 15-fold for the
      Cry1Ab protoxin and 108- and 484-fold for the Cry1Ab toxin. Activities of trypsin
      like, chymotrypsin-like and elastase-like proteinases were variable among the
      colonies tested and not indicative of a major contribution to Cry1Ab resistance.
      Activation of the 130-kDa Cry1Ab protoxin occurred rapidly in all colonies, with
      no apparent differences among colonies. In addition, there were no apparent
      changes in activated Cry1Ab processing, indicating that proteolytic degradation
      was not associated with resistance. These results suggest that mechanisms other
      than proteolytic activation of protoxin and toxin degradation, such as target
      site modification may be involved in the resistance to B thuringiensis Cry1Ab in
      these O nubilalis colonies.

PMID- 15578600
TI  - Dissipation of three organochlorine and four pyrethroid pesticides sprayed in a
      greenhouse environment during hydroponic cultivation of gerbera.
AB  - A wide range of pesticides (insecticides, acaricides and fungicides) is used in
      the hydroponic cultivation of gerbera. The fate and behaviour of some of these
      commonly used pesticides (organochlorine and pyrethroid insecticides/acaricides)
      in a greenhouse installation was investigated. The concentrations of endosulfan,
      dicofol, tetradifon, permethrin, bifenthrin, cypermethrin and deltamethrin in the
      air of the greenhouse were related to their physicochemical properties and
      respective application rates. Of these compounds, endosulfan exhibited the
      highest concentration in the greenhouse air 2 h after application (10 microg m(
      3)), due to its highest volatility; afterwards, up to 12 h post-application, a
      rapid decrease was recorded which finally led to a concentration of 0.41 microg
      m(-3) at 6 days post-application. Dicofol exhibited the same trend of dissipation
      in the greenhouse air; its concentration decreased from 0.27 microg m(-3)
      immediately after the application to 0.12 microg m(-3) at 6 days post
      application. Tetradifon, bifenthrin and permethrin were found at concentrations
      lower than 0.1 microg m(-3) at 2 h post-application, and cypermethrin and
      deltamethrin could not be detected. The concentrations of all the above
      pesticides in the drain water of the open hydroponic system were relatively high
      immediately after application and decreased rapidly during the following 3 days.
      In the closed hydroponic system, all the pesticides accumulated in the nutrient
      solution during the first 24 h after application and slowly decreased in
      concentration over the following 3 days. The spray operators applying these
      pesticides were exposed to rather high concentrations and the spray deposits were
      monitored on the chest and forehead of the operator. Endosulfan exhibited the
      highest concentrations of the seven pesticides. The organochlorine pesticides
      (endosulfan, dicofol and tetradifon) were usually detected at higher
      concentrations on the chest than on the forehead of the operator; pyrethroids
      were detected at higher concentrations on the forehead than on the chest of the
      operator.

PMID- 15578601
TI  - The impact of the herbicide glyphosate on leaf litter invertebrates within Bitou
      bush, Chrysanthemoides monilifera ssp rotundata, infestations.
AB  - Chrysanthemoides monilifera ssp rotundata (L) T Norl (Bitou bush) is a serious
      environmental weed along the southeast coast of Australia. The herbicide
      glyphosate is commonly used to control C monilifera on the New South Wales
      coastline, but there have been few studies examining the effects of this
      herbicide on invertebrate communities in the field, especially on sand dunes.
      Control and impact sites were selected in coastal hind dunes heavily infested
      with C monilifera, and the impact sites were sprayed with a 1:100 v/v dilution of
      glyphosate-isopropyl 360 g AE litre(-1) SL (Roundup Biactive). Leaf litter
      invertebrates were sampled before spraying and after spraying by collecting fixed
      areas of leaf litter in both the control and impact sites. Samples were sorted
      for particular invertebrates involved in leaf litter decomposition and some of
      their predators. This study did not identify any significant direct or indirect
      effects on leaf litter invertebrate abundance or community composition in the
      four months following herbicide application. The litter invertebrate assemblages
      were highly variable on a small spatial scale, with abiotic factors more strongly
      regulating leaf litter invertebrate numbers than glyphosate application. These
      results conflict with previous studies, indicating that the detrimental indirect
      effects herbicide application has on non-target litter invertebrates may depend
      upon the application rate, the vegetation community and structure and post-spray
      weather.

PMID- 15578602
TI  - Evaluation of selective toxicity of five pesticides against Plutella xylostella
      (Lep: Plutellidae) and their side-effects against Cotesia plutellae (Hym:
      Braconidae) and Oomyzus sokolowskii (Hym: Eulophidae).
AB  - The toxicities of five pesticides commonly used in vegetable fields to the larvae
      of the diamondback moth, Plutella xylostella (L) and its two major parasitoids,
      Cotesia plutellae (Kurdjumov) and Oomyzus sokolowskii (Kurdjumov), were evaluated
      in the laboratory using several bioassays. When tested at the rates recommended
      for field application by the manufacturer, fipronil, avermectin and
      chlorfluazuron produced over 95% mortality on third-instar larvae of P
      xylostella, but fenvalerate and methomyl did not produce any substantial
      mortality to such larvae, and over 70% of P xylostella larvae could still pupate
      normally after feeding on cabbage leaf treated with the two pesticides. In a
      residual contact assay with adult parasitoids, fipronil and methomyl caused over
      93% mortality within 24 h; fenvalerate killed approximately 55% of the adults
      within 24 h; avermectin and chlorfluazuron showed differential toxicity to the
      two parasitoids. Avermectin was extremely harmful to O sokolowskii but slightly
      toxic to C plutellae, while chlorfluazuron was more toxic to C plutellae than to
      O sokolowskii. In the residue assay with cocoons of C plutellae and pupae of O
      sokolowskii developed within P xylostella pupae, treatments with pesticides did
      not reduce adult emergence. However, the mortality of C plutellae adults emerged
      from the fipronil-treated cocoons increased greatly within 24 h post-emergence;
      adults from the fenvalerate-treated cocoons parasitized less host larvae.
      Treatments with fenvalerate and methomyl significantly increased the mortality of
      O sokolowskii adults within 24 h post-emergence. Recommendations of choosing
      pesticides for the control of P xylostella are given.

PMID- 15578603
TI  - Movement and biological activity of drip-applied 1,3-dichloropropene and
      chloropicrin in raised mulched beds in the southeastern USA.
AB  - Movement and biological activity of 1,3-dichloropropene (1,3-D) and chloropicrin
      applied through drip irrigation in raised beds was investigated at three
      locations in the southeastern USA. Tests were conducted in fields with dense
      populations of nutsedge (Cyperus spp), with one location also having a high level
      of soil nematodes, both of which served as biological indicators of the
      distribution of effective concentrations of 1,3-D and chloropicrin. Objectives
      were (1) to gain a better understanding of 1,3-D and chloropicrin movement and
      the extent of biological activity outside of the wetted bed area, and (2) to
      examine the effect of application rate, application concentration and subsequent
      irrigation events on movement and activity of 1,3-D and chloropicrin. InLine, an
      emulsifiable concentrate containing 60.8% w/w 1,3-D and 33.3% w/w chloropicrin,
      was injected into polyethylene mulched beds through the drip tubes and water
      movement in the beds was visualized by adding a blue dye to the injection system.
      Gas concentrations of 1,3-D and chloropicrin in soil were measured using Gastec
      detection tubes at different positions relative to the drip tube at 1-4 days
      after InLine application. After one week, mulch was removed and nutsedge survival
      evaluated at different positions in the bed. High concentrations of 1,3-D and
      chloropicrin were measured at the bed center and midway between the bed center
      and the shoulder, but concentrations were low at the bed shoulder. Width of
      nutsedge control was significantly greater than width of water movement. Plant
      parasitic nematodes were controlled over the entire bed width, but nutsedge re
      emerged at the bed shoulders regardless of treatment. Higher application rates
      and concentrations of 1,3-D + chloropicrin resulted in higher fumigant
      concentrations in soil air. Irrigations subsequent to application reduced soil
      air concentrations of 1,3-D and chloropicrin and increased water movement, as did
      the use of two drip tubes instead of one. The data show that the pesticidal
      activity of 1,3-D + chloropicrin extends beyond the waterfront and indicate a
      significant degree of fumigant activity of emulsifiable 1,3-D + chloropicrin.
      However, unlike plant-parasitic nematodes, nutsedge could not be controlled over
      the entire bed width, regardless of rate, concentration and volume of water
      applied.

PMID- 15578604
TI  - The contact toxicity of indoxacarb and five other insecticides to Orius
      insidiosus (Hemiptera: Anthocoridae) and Aphidius colemani (Hymenoptera:
      Braconidae), beneficials used in the greenhouse industry.
AB  - The contact toxicity of indoxacarb, abamectin, endosulfan, insecticide soap, S
      kinoprene and dimethoate to Orius insidiosus (Say) and Aphidius colemani Viereck
      were studied in the laboratory. These beneficials are often used in the
      greenhouses to manage various insect pests. Indoxacarb is slow acting and
      therefore, to estimate lethal dosages, observations should be continued for
      several days until data stabilize. Seven days after treatment, the LC50 was 0.119
      g AI litre(-1) for O insidiosus adults and 0.019 g AI litre(-1) for A colemani.
      At that time, the recommended field concentration was 0.479 times the LC50 for O
      insidiosus adults and three times the LC50 for A colemani. In contrast,
      indoxacarb had no adverse effect on the reproductive capacity of wasps surviving
      a treatment or the developing wasps in the aphid mummy. Among the other
      insecticides S-kinoprene was the most innocuous while dimethoate was the most
      toxic to the two beneficials. The other insecticides had overlapping toxicities.

PMID- 15578605
TI  - Bermudagrass (Cynodon spp) dose-response relationships with clethodim,
      glufosinate and glyphosate.
AB  - Greenhouse studies were conducted to evaluate the sensitivity of three commercial
      cultivars, eight experimental cultivars and common bermudagrass to clethodim,
      glufosinate and glyphosate. Each herbicide was applied at eight doses. Data were
      regressed on herbicide dose using a log-logistic curve (R2 = 0.56-0.95 for
      clethodim, R2 = 0.60-0.94 for glufosinate, and R2 = 0.70-0.96 for glyphosate).
      The herbicide rate that elicited a 50% plant response (I50) in the bermudagrass
      cultivars ranged from 0.04 to 0.19 kg ha(-1) clethodim, 0.19 to 1.33 kg ha(-1)
      glufosinate and 0.34 to 1.14 kg ha(-1) glyphosate. Relative to other cultivars,
      common bermudagrass was intermediate in its response to clethodim and among the
      most tolerant cultivars to glufosinate and glyphosate. TifSport was relatively
      tolerant to clethodim and glufosinate compared with other cultivars, but
      relatively sensitive to glyphosate. One cultivar, 94-437, was consistently among
      the most sensitive cultivars to each of the herbicides. While there were
      differential herbicide tolerances among the tested bermudagrass cultivars, there
      did not appear to be any naturally occurring herbicide resistance that could be
      commercially utilized. However, research indicated that breeding efforts should
      target herbicide resistance that is at least four times the registered use rate.
      Also, TifSport and Tifway have been identified as suitable representatives of
      triploid hybrid bermudagrass cultivars to be used to evaluate the success of
      turfgrass renovation programs.

PMID- 15578606
TI  - Meta-analysis of the association between two polymorphisms in the serotonin
      transporter gene and affective disorders.
AB  - Family, twin, and adoption studies show that psychiatric diseases including
      bipolar disorder (BP) and unipolar disorder (UP) have a substantial genetic
      component. For these illnesses, both positive and negative associations have been
      reported for two polymorphisms located in the serotonin transporter gene (5-HTT)
      on chromosome 17: a 17-base-pair (bp) variable-number tandem-repeat (VNTR) in
      intron 2 and a 44-bp insertion/deletion in the promoter region. Thus,
      associations between these 5-HTT polymorphisms and affective disorders remain
      unclear. The present work investigates these potential associations in meta
      analyzes that maximize the power to find associations between each disease and
      the two 5-HTT polymorphisms. We applied meta-analysis techniques to case-control
      studies of two 5-HTT polymorphisms and two affective disorders (BP and UP),
      resulting in four meta-analyzes. For each polymorphism, we assessed the evidence
      for allelic associations, heterogeneity among studies, the influence of
      individual studies, and the potential for publication bias. The short allele(s)
      of the 44-bp insertion/deletion polymorphism showed a significant association for
      BP (odds ratio (OR) = 1.13, P = 0.001) but not UP. For the 17-bp VNTR, an
      increase in the number of tandem repeats had no significant association with any
      of the disorders. The small but significant effects of the 44-bp
      insertion/deletion polymorphism for BP is consistent with being one of many genes
      that contributes to the multi-factorial nature of these psychiatric disorders.

PMID- 15578608
TI  - Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in
      Chinese Han subjects.
AB  - Serotonin is an endogenous neurotransmitter that regulates aggressive and
      impulsive behavior and may be involved in the development of attention deficit
      hyperactivity disorder (ADHD). 5-HT1B knockout mice display hyperactivity,
      increased exploratory activity and aggression, reduced anxiety, increased
      vulnerability to cocaine self-administration, and elevated alcohol consumption.
      Many of these same behaviors are seen in patients with ADHD. Prior studies
      reported excess transmission of the 861G allele of 5-HT1B to ADHD offspring. We
      used the transmission disequilibrium test (TDT) and haplotype analysis to
      investigate the A-161T and G861C polymorphisms in the 5-HT1B receptor gene in
      ADHD trios from the Chinese Han population. We found no association with ADHD but
      did find a tendency for excess transmission of the 861G allele (chi(2) = 3.766, P
      = 0.052) and the G/A haplotype (chi(2) = 2.925, df = 1, P = 0.087), and under
      transmission of C/A haplotype (chi(2) = 3.707, df = 1, P = 0.054) to offspring
      with inattentive ADHD.

PMID- 15578609
TI  - Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing
      to individual differences in an anxiety-related personality trait: TPQ harm
      avoidance.
AB  - The chromosome 8p region is of interest in human behavioral genetics since it
      harbors a susceptibility region not only for schizophrenia but also for anxiety
      related personality traits such as harm avoidance and neuroticism. Towards
      verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at
      chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377
      families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an
      associated one parameter model), we observed significant results (P values from
      0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint
      LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region
      wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position
      varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two
      other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM
      of the peak for harm avoidance. This marker is of particular interest since it is
      proximate (<0.5 cM) of the core haplotype that in several recent studies show
      significant association with schizophrenia near neuroregulin 1. Although
      association studies with microsatellite markers need to be interpreted
      cautiously, using the Haplotype Trend Regression test one marker, D8S499 (
      approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3,
      which confers a decreased harm avoidance score. Altogether, the current linkage
      and association results suggest the possibility that the same locus near the
      neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related
      personality trait as well as schizophrenia. We hypothesize that this common
      genetic factor may contribute to emotional liability during early development,
      which constitutes a predisposing factor for major psychosis.

PMID- 15578610
TI  - Bindewald syndrome: Tetralogy of Fallot, large ears, severe growth and mental
      retardation.

PMID- 15578612
TI  - Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention
      deficit/hyperactivity disorder (ADHD): increased prevalence of the 2-repeat
      allele.
AB  - There is an increased prevalence of the 7-repeat (7R) allele of the dopamine
      receptor D4 (DRD4) gene in attention-deficit/hyperactivity disorder (ADHD).
      However, the population prevalence of the 7R allele varies considerably across
      ethnicity and is very low in Asians. To test whether this 7R allele/ADHD
      association still held in a Chinese clinical sample, 32 Han Chinese children with
      a confirmed ADHD diagnosis and normal IQ who were methylphenidate-responders were
      genotyped. None of them had a DRD4 7R allele. Instead, we observed a
      significantly increased prevalence of the 2-repeat (2R) allele in this clinical
      sample (33%) compared to ethnically-matched controls (20%) (chi(2)(1d.f.) = 5.90,
      P = 0.015). This approximately 1.65-fold increase of the 2R allele in our
      probands is close to the observed increase of the 7R allele in European-ancestry
      ADHD children. Recent genetic studies have indicated that the 2R allele in Asians
      is likely derived from the 7R allele. Further, available biochemical data
      indicate that both the 2R and 7R protein have blunted responses to dopamine
      compared to the 4R protein. Based on these results, we propose that the observed
      increased prevalence of the 2R allele in our Han Chinese ADHD probands is still
      consistent with the 7R allele hypothesis of ADHD in European-ancestry children.
      Recent studies have suggested that any variant from the conserved ancestral 4R
      allele might potentially alter biochemistry/phenotype. We hypothesize that an
      increased frequency of any non-4R allele may define the association of the DRD4
      gene with ADHD that holds across ethnicity. The present findings, however,
      obtained with a small ADHD sample size, should be replicated.

PMID- 15578613
TI  - Quantitative trait locus analysis of candidate gene alleles associated with
      attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5,
      SNAP-25, and 5HT1B.
AB  - It has been widely postulated that the categorical diagnosis of attention deficit
      hyperactivity disorder (ADHD) should be seen as the extreme end of a set of
      traits quantitatively distributed in the general population. A consequence of
      this is that the genes associated with DSM-IV ADHD should also influence these
      underlying traits in non-affected individuals. The aim of this study was to
      examine if specific candidate loci previously shown to be associated with DSM-IV
      ADHD, also act as quantitative trait loci (QTLs) for ADHD-symptoms in the general
      population. We have genotyped five candidate markers in a population-based sample
      of male dizygous twin-pairs (n = 329 pairs). We found little evidence to support
      a role for the previously-nominated alleles of a DRD4 VNTR, a 5HT1B SNP, or a
      microsatellite marker near to DRD5, in the distribution of ADHD-symptoms scores;
      however, we found some evidence to suggest that the DAT1 3'UTR VNTR and weak
      evidence that a microsatellite in SNAP-25 may have a role in continuous measures
      of ADHD-symptoms hyperactivity above and beyond their role in clinical ADHD.

PMID- 15578614
TI  - Kabuki syndrome is not caused by an 8p duplication: a cytogenetic study in 20
      patients.
AB  - Kabuki syndrome is characterized by a typical facial gestalt in combination with
      hypotonia and joint laxity, developmental delay, persistent fetal fingertip pads,
      and structural abnormalities mainly of the palate and the heart. Cytogenetic
      conditions may present with features of the syndrome. Recently, Milunsky and
      Huang [2003], reported an 8p duplication at chromosome 8p22-8p23.1 in 6 patients
      with Kabuki syndrome. We studied 20 individuals with Kabuki syndrome and were not
      able to confirm this finding. Kabuki syndrome remains a clinical diagnosis in the
      majority of cases.

PMID- 15578615
TI  - Expressive language in children with Kabuki syndrome.
AB  - Since the description of Kabuki syndrome in 1981 over 300 cases from a variety of
      countries have been reported. Only a limited number of these reports, however,
      provided data on speech language development. Ghent University Hospital (J. Van
      Borsel, T. Defloor) and the Department of Clinical Genetics, Academic Hospital
      Maastricht (C.T.R.M. Schrander-Stumpel, L.M.G. Curfs) are directing research on
      the specific nature of communicative development in persons with Kabuki syndrome.
      The aim of the present study was to delineate the language difficulties in the
      syndrome. The subjects were six Dutch-speaking children (three male, three
      female), with chronological age ranging from 4.4 to 10.6 years (mean = 8.1).
      Spontaneous speech samples were collected, subjected to a consensus orthographic
      transcription, and analyzed by means of TOAST [Moerman-Coetsier and Van Besien,
      1987], a Dutch standardized diagnostic instrument to investigate different
      aspects of spontaneous language production. In all the children, expressive
      language abilities were impaired. Poor morphosyntactic abilities were
      consistently demonstrated. Lexical and pragmatic difficulties were also present,
      whereas phonological development was less often affected.

PMID- 15578616
TI  - Severe, neonatal-onset OTC deficiency in twin sisters with a de novo balanced
      reciprocal translocation t(X;5)(p21.1;q11).
AB  - OTC deficiency, the most common urea cycle defect, is transmitted as a partially
      dominant X-linked trait. The most severe form of the disease, however, is usually
      restricted to males. We report on monozygotic female twins with severe neonatal
      onset OTC deficiency and a de novo balanced reciprocal translocation
      t(X;5)(p21.1;q11). Disruption of the OTC gene on the derivative X-chromosome was
      confirmed by FISH analysis. Consistent inactivation of the normal X could be
      demonstrated by RGB staining. Manifestation of X-linked recessive disorders in
      females due to a balanced reciprocal X-autosome translocation has previously been
      described in Duchenne muscular dystrophy and several other disorders but not in
      OTC deficiency. This report emphasizes the importance of chromosome analysis in
      any female manifesting severe OTC deficiency.

PMID- 15578617
TI  - Iris heterochromia: a variable feature in Verloes-Koulischer-oral-acral syndrome.

PMID- 15578618
TI  - Down syndrome with pure partial trisomy 21q22 due to a paternal insertion (4;21)
      uncovered by uncultured amniotic fluid interphase FISH.
AB  - OBJECTIVE: To emphasize the usefulness and reliability of fluorescence in situ
      hybridization (FISH) on uncultured amniotic fluid cells in the prenatal diagnosis
      of common chromosomal aneuploidies. METHODS: FISH analyses utilizing centromeric,
      locus-specific or whole chromosome paint DNA probes specific for chromosomes X,
      Y, 13, 18, 21, and 4 were performed on uncultured amniotic fluid cells or the
      peripheral blood specimen from the father. Routine chromosome analysis was
      carried out as well. RESULTS: A prenatal case with partial trisomy 21 due to a
      paternal cryptic insertion (4;21) was ascertained by a rapid overnight FISH on
      uncultured amniotic fluid cells. The fetus was delivered at term and had
      classical features of Down syndrome. CONCLUSION: Our results stress the
      importance of FISH on uncultured amniotic fluid cells to supplement routine
      cytogenetics, especially in cases with abnormal ultrasound findings.

PMID- 15578619
TI  - Subtelomeric 6p deletion: clinical, FISH, and array CGH characterization of two
      cases.
AB  - Thirty patients have been described with cytogenetically visible deletion of the
      short arm of chromosome 6. However, subtelomeric 6p deletion detected by
      subtelomeric specific probes has been reported only twice. We report two new
      patients with terminal 6p deletion detected by subtelomeric screening using
      fluorescence in situ hybridization (FISH). The two patients exhibited mental
      retardation, ocular abnormalities, hearing loss, and a characteristic facial
      appearance. Detailed FISH analyses with probes covering the distal 6p25 region
      estimated the size of the terminal deletions to approximately 5.5 Mb and
      approximately 4.8 Mb. Array-based comparative genomic hybridization (array CGH)
      was used to confirm the cryptic deletions. Most patients with subtelomeric
      defects lack a characteristic phenotype. However, some of the subtelomeric
      deletions result in a specific phenotype, which can direct the clinician towards
      the diagnosis. Submicroscopic 6p deletion appears to be a recognizable clinical
      phenotype, and this region should be thoroughly investigated with FISH probes,
      including at least a subtelomeric 6p probe and a probe covering FOXC1, for
      patients presenting with a characteristic facial appearance, ocular
      abnormalities, predominantly anterior-chamber eye defects, hearing loss, and
      mental retardation.

PMID- 15578620
TI  - Carbimazole embryopathy: an emerging phenotype.
AB  - Concerns about the safety of carbimazole in pregnancy were raised in 1985. Since
      this time many reports of children believed to have been affected by carbimazole
      in utero have appeared in the medical literature. Initial reports were of an
      increased incidence of scalp defects in the infants of treated mothers, but many
      other anomalies have now been described. Choanal atresia, gastrointestinal
      anomalies-particularly esophageal atresia, athelia/hypothelia, developmental
      delay, hearing loss, and dysmorphic facial features have all been reported. The
      phenotype associated with exposure to carbimazole appears to be rare but specific
      with distinctive facial features. We report on two new cases of carbimazole
      embryopathy with strikingly similar facial features.

PMID- 15578621
TI  - The PTPN11 gene is not implicated in nonsyndromic hypertrophic cardiomyopathy.

PMID- 15578622
TI  - Efficacy and medical cost offset of psychosocial interventions in cancer care:
      making the case for economic analyses.
AB  - The burden of cancer in the worldwide context continues to grow, as incidence and
      mortality increase each year. Regardless of where they live, a significant
      proportion of cancer patients at all stages of the disease trajectory will suffer
      social, emotional and psychological morbidity as a result of their diagnosis and
      treatment. Psychosocial interventions have proven efficacious in helping patients
      and families overcome many of the challenges that arise consequent to a cancer
      diagnosis. Addressing psychosocial needs is an essential aspect of any model of
      adequate cancer care, however it may also prove to be a cornerstone in efforts to
      extend the reach of cost-effective cancer treatment to meet the growing global
      need. In order to set the stage for discussion of economic issues, this paper
      first briefly reviews the literature detailing the extent of distress and the
      efficacy of psychosocial treatments for cancer patients. This is followed by a
      summary of terminology and costing concepts in the economic evaluation of
      psychosocial treatments, and a review of the literature on medical cost offset in
      mental health, other medical populations, and in cancer patients. The literature
      clearly supports the notion that psychosocial interventions are not only
      effective, but also economical. Conclusions support adding costing data into
      evaluations of the efficacy of psychosocial treatments in order to detail the
      often present but usually overlooked long-term cost savings that may be accrued
      to overburdened health-care systems.

PMID- 15578624
TI  - A locus for Bowen-Conradi syndrome maps to chromosome region 12p13.3.
AB  - Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive disorder with an
      estimated incidence of 1 in 355 live births in the Hutterite population. A few
      cases have been reported in other populations. Here, we report the results of a
      genome-wide scan and fine mapping of the BCS locus in Hutterite families. By
      linkage and haplotype analysis the BCS locus was mapped to a 3.5 cM segment (1.9
      Mbp) in chromosome region 12p13.3 bounded by F8VWF and D12S397. When genealogical
      relationships among the families were taken into account in the linkage analysis,
      the evidence for linkage was stronger and the number of potentially linked
      regions was reduced to one. Under the assumption that all the Hutterite patients
      were identical by descent for a disease-causing mutation, haplotype analysis was
      used to infer likely historical recombinants and thereby narrow the candidate
      region to a chromosomal segment shared in common by all the affected children.
      This study also demonstrates that BCS and cerebro-oculo-facial-skeletal syndrome
      (COFS) are genetically distinct.

PMID- 15578625
TI  - Velocardiofacial syndrome with single central incisor.
AB  - Three siblings and their mother are reported who all had cytogenetically proven
      velocardiofacial syndrome (VCFS). One boy had normal dental and craniofacial
      findings, except for an increased cranial base angle. His sister had only one
      central incisor in the maxilla. One central incisor had also been missing in the
      primary dentition. She had no labial frenulum present. Cephalometry showed a
      small maxillary unit length indicating mild maxillary hypoplasia, an increased
      anterior face height, steep mandibular plane angle, retruded chin, and a large
      cranial base angle. Dental measurements showed retroclined lower incisors and
      increased interincisal angle. A second sister had a cleft of the secondary
      palate. All permanent teeth were present with the exception of a missing central
      incisor in the lower jaw: the single lower central incisor was situated in the
      midline. Her cephalometry showed similar findings as in her sister. All three
      siblings required palate surgery for speech. Mother was not available for
      detailed dental and other oral investigations. A single maxillary central incisor
      has previously been reported in VCFS, but to our knowledge a single central
      incisor in the mandible has not been reported previously in this entity.

PMID- 15578626
TI  - Overactive bladder and painful bladder syndrome: there need not be confusion.

PMID- 15578627
TI  - Psychometric properties and validation of the German-language King's Health
      Questionnaire in women with stress urinary incontinence.
AB  - AIMS: The purpose of this study was to evaluate the psychometric properties of
      and validate the German-language version of the King's Health Questionnaire (KHQ)
      in women with stress urinary incontinence (SUI). METHODS: A total of 145 women
      treated for stress incontinence with surgery or physiotherapy completed the the
      KHQ and the SF-36 before and after treatment. Psychometric analyses of the
      quality of life (QoL) instruments determined the reliability (Cronbach's alpha),
      internal and external validity, and responsiveness of the KHQ subscales. RESULTS:
      The KHQ showed good internal consistency, content validity, and criterion
      validity as measured by correlation with scores on the SF-36. Cronbach's alpha
      coefficient ranged from 0.76 to 0.86, indicating a high internal consistency of
      the subscales. Concerning criterion validity, correlations between the KHQ
      subscales and the SF-36 were low to moderate. The highest correlation was found
      between the general health perception subscales of both questionnaires.
      CONCLUSIONS: The results indicate good psychometric properties for the German
      language KHQ.

PMID- 15578628
TI  - Botulinum toxin for the treatment of lower urinary tract symptoms: a review.
AB  - AIMS: To review the available literature on the application of botulinum toxin in
      the urinary tract, with particular reference to its use in treating detrusor
      overactivity (DO). METHODS: Botulinum toxin, overactive bladder (OAB), detrusor
      instability, DO, detrusor sphincter dyssynergia (DSD), and lower urinary tract
      dysfunction were used on Medline Services as a source of articles for the review
      process. RESULTS: DO poses a significant burden on patients and their quality of
      life. Traditionally patients have been treated with anti-cholinergic drugs if
      symptomatic, however, a significant number find this treatment either ineffective
      or intolerable due to side effects. Recent developments in this field have
      instigated new treatment options, including botulinum toxin, for patients'
      refractory to first line medication. Botulinum toxin, one of the most poisonous
      substances known to man, is a neurotoxin produced by the bacterium Clostridium
      botulinum. Botulinum toxin injections into the external urethral sphincter to
      treat detrusor sphincter dyssynergia has been successfully used for some years
      but recently its use has expanded to include voiding dysfunction. Intradetrusal
      injections of botulinum toxin into patients with detrusor overactivity and
      symptoms of the overactive bladder have resulted in significant increases in mean
      maximum cystometric capacity and detrusor compliance with a reduction in mean
      maximum detrusor pressures. Subjective and objective assessments in these
      patients has shown significant improvements that last for 9-12 months. Repeated
      injections have had the same sustained benefits. CONCLUSIONS: Application of
      botulinum toxin in the lower urinary tract has produced promising results in
      treating lower urinary tract dysfunction, which needs further evaluation with
      randomised, placebo-controlled trials.

PMID- 15578629
TI  - Functional impairment as a risk factor for urinary incontinence among older
      Americans.
AB  - AIMS: Using a large nationally representative sample of older Americans we
      investigate four domains of functional impairment as possible risk factors for
      the subsequent development of urinary incontinence (UI) symptoms. METHODS: Data
      from three waves (1993, 1995, 1998) of the Asset and Health Dynamics among the
      Oldest Old (AHEAD) survey were used to model the effects of functional impairment
      on the onset of UI symptoms. RESULTS: A greater number of serious chronic
      conditions and functional impairment in the lower body mobility domain increased
      the odds of the onset of mild UI (vs. remaining continent). Factors that
      contributed to greater odds of the onset of severe UI (vs. remaining continent)
      were older age, being represented by a proxy respondent, and functional
      impairment in the strength domain. CONCLUSIONS: Understanding the possible
      relationship between functional impairment and UI is an important step toward
      developing appropriate interventions for the prevention, treatment, or management
      of urine loss.

PMID- 15578632
TI  - Ticlopidine quantification in human plasma by high-performance liquid
      chromatography coupled to electrospray tandem mass spectrometry. Application to
      bioequivalence study.
AB  - A rapid, sensitive and specific method to quantify ticlopidine in human plasma
      using clopidogrel as the internal standard (IS) is described. The analyte and the
      IS were extracted from acidified plasma by liquid-liquid extraction using diethyl
      ether-hexane (80 : 20, v/v). The extracts were analyzed by high-performance
      liquid chromatography coupled to electrospray tandem mass spectrometry
      (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C(8)
      4 microm analytical column (150 x 4.1 mm i.d.). The method had a chromatographic
      run time of 3.0 min and a linear calibration curve over the range 1.0-1000 ng ml(
      1) (r(2) > 0.999427). The limit of quantification was 1.0 ng ml(-1). This
      HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250
      mg tablet formulations (ticlopidine test formulation from Apotex do Brasil,
      Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A
      single 250 mg dose of each formulation was administered to healthy volunteers.
      The study was conducted using an open, randomized, two-period crossover design
      with a 2 week washout interval. Since the 90% confidence interval for C(max) and
      area under the curve ratios were all inside the 80-125% interval proposed by the
      US Food and Drug Administration, it was concluded that ticlopidine formulation
      from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both
      the rate and the extent of absorption.

PMID- 15578633
TI  - Donor-acceptor properties of isonitriles studied by photoelectron spectroscopy
      and electron transmission spectroscopy.
AB  - Some alkyl and aryl isonitriles, considered as CO analogue sigma-donor and pi
      acceptor ligands in transition metal chemistry, were studied by means of HeI
      photoelectron spectroscopy and electron transmission spectroscopy, in order to
      evaluate their donor-acceptor properties from the measured ionization energies
      (IE) and vertical electron attachment energies (VAE). The investigated molecules
      were 2-propyl, 1-butyl, tert-butyl, 1-pentyl, cyclohexyl, 2,6-dimethylphenyl, 4
      methoxyphenyl and 4-chorophenyl isonitrile. By interpreting the spectra on the
      basis of literature data and quantum chemical calculations, the spectral features
      associated with the molecular orbitals mainly involved in coordination and back
      donation were identified. The results show that the IE (10.62-10.95 eV) of the
      sigma electron pair (n(c)) responsible for the sigma-donor capability is
      substantially lower than that of CO. The VAEs of the empty pi* orbitals involved
      in the d/pi* back-donation indicate that aryl isonitriles are better acceptors
      (VAE <0.3 eV) than their aliphatic counterparts (VAE >2.7 eV). In the case of
      aryl derivatives, the pi-donor ability could also play some role in metal-ligand
      bonding (IE 8.74-9.34 eV). Isonitrile coordination characteristics are also
      compared with those of CO, N(2) and CH(3)CN.

PMID- 15578634
TI  - Exploring the active-site of a rationally redesigned lipase for catalysis of
      Michael-type additions.
AB  - Michael-type additions of various thiols and alpha,beta-unsaturated carbonyl
      compounds were performed in organic solvent catalyzed by wild-type and a
      rationally redesigned mutant of Candida antarctica lipase B. The mutant lacks the
      nucleophilic serine 105 in the active-site; this results in a changed catalytic
      mechanism of the enzyme. The possibility of utilizing this mutant for Michael
      type additions was initially explored by quantum-chemical calculations on the
      reaction between acrolein and methanethiol in a model system. The model system
      was constructed on the basis of docking and molecular-dynamics simulations and
      was designed to simulate the catalytic properties of the active site. The
      catalytic system was explored experimentally with a range of different
      substrates. The kca values were found to be in the range of 10(-3) to 4 min(-1),
      similar to the values obtained with aldolase antibodies. The enzyme proficiency
      was 10(7). Furthermore, the Michael-type reactions followed saturation kinetics
      and were confirmed to take place in the enzyme active site.

PMID- 15578635
TI  - Direct analysis of some diamines in food simulants used for migration tests by
      electrospray ionization tandem mass spectrometry.

PMID- 15578636
TI  - Identification of indigoid dyes in natural organic pigments used in historical
      art objects by high-performance liquid chromatography coupled to electrospray
      ionization mass spectrometry.
AB  - Pigments are among the most important components of historical paintings and
      textiles and their nature provides the unique character of color. They can be
      divided into two main groups: inorganic and organic, extracted from plants or
      animals. Their identification is a necessary stage in the conservation of art
      objects. Reversed-phase liquid chromatography with electrospray ionization mass
      spectrometry (ESI-MS) and UV/visible spectrophotometric methods were elaborated
      for the identification of indigoid (indigo, indirubin, isoindigo, isoindirubin)
      color components of natural dyestuffs and their natural or synthetic precursors
      (indican, isatin, indoxyl, 2-indolinone). ES-MS offers detection limits in the
      range 0.03-5.00 microg ml(-1) for the color compounds examined. The method
      developed made it possible to identify indigo and its isomers in genuine Indian
      indigo, indigo from woad and Tyrian Purple. It was applied to the identification
      of natural dyes on fiber from a 19th century Japanese tapestry, 'Cranes in the
      landscape'. A procedure based on freezing and grinding of a sample before the
      extraction of dyes from the textile was developed. The components of the extract
      obtained were identified after acidic hydrolysis as indigotin and methylene blue.

PMID- 15578637
TI  - Tandem mass spectrometry of intact oxidation products of
      diacylphosphatidylcholines: evidence for the occurrence of the oxidation of the
      phosphocholine head and differentiation of isomers.
AB  - Three glycerophosphatidylcholine (GPC) phospholipids (oleoyl-, linoleoyl- and
      arachidonoylpalmitoylphosphatidylcholine) were oxidized under Fenton reaction
      conditions (H(2)O(2) and Fe(2+)), and the long-chain oxidation products were
      detected by electrospray mass spectrometry (ES-MS) and characterized by ES-MS/MS.
      The intact oxidation products resulted from the insertion of oxygen atoms into
      the phospholipid structure. The tandem mass spectra of the [MNa](+) molecular ion
      showed, apart from the characteristic fragments of GPC, fragment ions resulting
      from neutral losses from [MNa](+), and combined with loss of 59 and 183 Da from
      [MNa](+). These ions resulted from cleavage of the bond near the hydroxy group by
      a charge-remote fragmentation mechanism, allowing its location to be pinpointed.
      The fragments thus formed reflected the positions of the double bonds and of the
      derivatives along the unsaturated fatty acid chain, giving very useful
      information, as they allowed the presence of structural isomers and positional
      isomers to be established. The identification of the fragment ion at m/z 163,
      which is 16 Da higher than the five-membered cyclophosphane ion (m/z 147), in
      some tandem mass spectra, is consistent with the oxidation of the phosphocholine
      head. Some ions were found to occur with the same m/z value; in two of the
      phospholipids and based on the MS/MS data, structural and positional isomers were
      differentiated. Our findings indicate that MS/MS is a valuable tool for the
      identification of the wide complexity of structural features occurring in
      oxidized phosphatidylcholines during lipid peroxidation in cellular membranes.

PMID- 15578638
TI  - Different behavior of dextrans in positive-ion and negative-ion mass
      spectrometry.
AB  - A mass spectrometric (MS) comparative study of dextran samples using two
      different ionization techniques (matrix-assisted laser desorption/ionization
      (MALDI) and electrospray ionization (ESI)) in both positive- and negative-ion
      modes is reported. The experiments were carried out with two polydisperse
      dextrans (1000 and 8800 Da) and isomaltotriose. In the positive-ion mode, the
      expected alkali metal ion adducts of dextrans were observed in both techniques.
      In contrast, the expected preferential formation of deprotonated molecules [M -
      H](-) was not confirmed in negative mode MALDI time-of-flight (TOF) MS, where the
      series of ions [M(x)- H +42](-) or [M(x+1)- H - 120](-), coming either from some
      addition or fragmentation, were observed. In both ionization techniques, these
      ions formed the main distributions of dextrans in the negative-ion mode. It seems
      that the negative molecular ions formed from the alpha1 --> 6 linkage of
      polyglucose oligomers easily decompose, and the product ions [M - H - 120](-)
      markedly dominate. The fragmentation experiments and especially the investigation
      of the fundamental role of the nozzle-skimmer potential in ESI-MS supported our
      explanation of the observed behavior because its higher values caused higher
      fragmentation. The experiments with isomaltotriose excluded any addition of 42 Da
      during the MS procedures, which is not distinguishable from the loss of 120 Da in
      the case of polydisperse dextrans. MALDI-TOFMS was found to be more sensitive for
      the detection of higher oligosaccharides and ESI-MS more useful for structural
      studies.

PMID- 15578642
TI  - A new chemical probe for proteomics of carbohydrate-binding proteins.

PMID- 15578643
TI  - Antioxidative effects of flavonols and their glycosides against the free-radical
      induced peroxidation of linoleic acid in solution and in micelles.
AB  - The antioxidative effect of flavonols and their glycosides against the
      peroxidation of linoleic acid has been studied in homogeneous solution
      (tBuOH/H(2)O, 3:2) and in sodium dodecyl sulfate and cetyl trimethylammonium
      bromide micelles. The peroxidation was initiated thermally by the water-soluble
      initiator 2,2'-azobis(2-methylpropionamidine) dihydrochloride, and the reaction
      kinetics were studied by monitoring the formation of linoleic acid
      hydroperoxides. The synergistic antioxidant effect of the flavonols with alpha
      tocopherol (vitamin E) was also studied by following the decay kinetics of alpha
      tocopherol and the alpha-tocopheroxyl radical. Kinetic analysis of the
      antioxidative process demonstrates that the flavonols are effective antioxidants
      in solution and in micelles, either alone or in combination with alpha
      tocopherol. The antioxidative action involves trapping the initiating radicals in
      solution or in the bulk-water phase of the micelles, trapping the propagating
      lipid peroxyl radicals on the surface of the micelles, and regenerating alpha
      tocopherol by reducing the alpha-tocopheroxyl radical. It was found that the
      antioxidant activity of the flavonols and their glycosides depends significantly
      on the position and number of the hydroxy groups, the oxidation potential of the
      molecule, and the reaction medium. The flavonols bearing ortho-dihydroxy groups
      possess significantly higher antioxidative activity than those without such
      functionalities, and the glycosides are less active than their parent aglycones.
      The activity of the flavonols is higher in micelles than in solution, while the
      activity of alpha-tocopherol is lower in micelles than in solution. This is
      because the predominant factor for controlling the activity is the hydrogen
      bonding interaction of the antioxidant with the micellar surface in the case of
      hydrophilic flavonols, while it is the inter- and intramicellar diffusion in the
      case of lipophilic alpha-tocopherol.

PMID- 15578644
TI  - Dissecting the intimate mechanism of cyanation of {2Fe3S} complexes related to
      the active site of all-iron hydrogenases by DFT analysis of energetics,
      transition states, intermediates and products in the carbonyl substitution
      pathway.
AB  - A bridging carbonyl intermediate with key structural elements of the diiron sub
      site of all-iron hydrogenase has been experimentally observed in the CN/CO
      substitution pathway of the {2Fe3S} carbonyl precursor,
      [Fe(2)(CO)(5){MeSCH(2)C(Me)(CH(2)S)(2)}]. Herein we have used density functional
      theory (DFT) to dissect the overall substitution pathway in terms of the
      energetics and the structures of transition states, intermediates and products.
      We show that the formation of bridging CO transitions states is explicitly
      involved in the intimate mechanism of dicyanation. The enhanced rate of
      monocyanation of {2Fe3S} over the {2Fe2S} species
      [Fe(2)(CO)(6){CH(2)(CH(2)S)(2)}] is found to rest with the ability of the
      thioether ligand to both stabilise a mu-CO transition state and act as a good
      leaving group. In contrast, the second cyanation step of the {2Fe3S} species is
      kinetically slower than for the {2Fe2S} monocyanide because the Fe2 atom is
      deactivated by coordination of the electron-donating thioether group. In
      addition, hindered rotation and the reaction coordinate of the approaching CN(-)
      group, are other factors which explain reactivity differences in {2Fe2S} and
      {2Fe3S} systems. The intermediate species formed in the second cyanation step of
      {2Fe3S} species is a mu-CO species, confirming the structural assignment made on
      the basis of FT-IR data (S. J. George, Z. Cui, M. Razavet, C. J. Pickett, Chem.
      Eur. J. 2002, 8, 4037-4046). In support of this we find that computed and
      experimental IR frequencies of structurally characterised {2Fe3S} species and
      those of the bridging carbonyl intermediate are in excellent agreement. In a
      wider context, the study may provide some insight into the reactivity of
      dinuclear systems in which neighbouring group on-off coordination plays a role in
      substitution pathways.

PMID- 15578645
TI  - Study of the DNA/ethidium bromide interactions on mica surface by atomic force
      microscope: influence of the surface friction.
AB  - The influence of mica surface on DNA/ethidium bromide interactions is
      investigated by atomic force microscopy (AFM). We describe the diffusion
      mechanism of a DNA molecule on a mica surface by using a simple analytical model.
      It appears that the DNA diffusion on a mica surface is limited by the surface
      friction due to the counterion correlations between the divalent counterions
      condensed on both mica and DNA surfaces. We also study the structural changes of
      linear DNA adsorbed on mica upon ethidium bromide binding by AFM. It turns out
      that linear DNA molecules adsorbed on a mica surface are unable to relieve the
      topological constraint upon ethidium bromide binding. In particular, strongly
      adsorbed molecules tend to be highly entangled, while loosely bound DNA molecules
      appear more extended with very few crossovers. Adsorbed DNA molecules cannot move
      freely on the surface because of the surface friction. Therefore, the topological
      constraint increases due to the ethidium bromide binding. Moreover, we show that
      ethidium bromide has a lower affinity for strongly bound molecules due to the
      topological constraint induced by the surface friction.

PMID- 15578646
TI  - Methanol, formaldehyde, and sodium formate exposure in rat and mouse conceptuses:
      a potential role of the visceral yolk sac in embryotoxicity.
AB  - BACKGROUND: Methanol (CH3OH) is believed to be teratogenic based on rodent
      studies. The mouse is more sensitive than the rat, but mechanisms of toxicity and
      identification of teratogenic metabolites are uncertain. METHODS: Rat and mouse
      whole embryo cultures are used to distinguish toxicity of CH3OH and its
      metabolites, formaldehyde (HCHO) and formate (HCOONa), which are produced
      following transit through the visceral yolk sac (VYS), via addition to culture
      medium, or by direct embryonic exposure through microinjection into the amnion.
      RESULTS: Embryonic viability, increased dysmorphogenesis, and decreased growth
      parameters were altered in a dose-dependent fashion for each compound. Mouse
      embryos were more sensitive than rat, as indicated by significant decreases in
      viability at comparable, lower concentrations. HCHO produced dysmorphogenesis and
      caused embryolethality at nearly 1000-fold lower concentrations (0.004 mg/ml)
      than seen with either CH3OH or HCOONa. All agents produced incomplete axial
      rotation and delayed neural tube closure in mice, but only CH3OH elicited similar
      effects in the rat. Increased growth retardation, blood pooling in the head and
      VYS, enlarged pericardium, accumulation of necrotic matter in the amnion, and
      hypoplastic prosencephalon were observed in both species with all compounds.
      Microinjection of compounds into the amnion produced higher mortality in mouse
      and rat, compared to equimolar amounts added to the culture medium. CH3OH did not
      prevent neural tube closure in the rat when microinjected. CONCLUSIONS: HCHO is
      the most embryotoxic CH3OH metabolite and elicits the entire spectrum of lesions
      produced by CH3OH. The VYS serves a general protective role against toxicity and
      inherent differences in the embryonic metabolism of CH3OH may determine species
      sensitivity.

PMID- 15578647
TI  - Enhancing growth human endothelial cells on Arg-Gly-Asp (RGD) embedded poly
      (epsilon-caprolactone) (PCL) surface with nanometer scale of surface disturbance.
AB  - To explore the application of PCL for the engineering of soft tissues, the PCL
      surface was first embedded in an amphiphilic moiety and then grafted with RGD
      peptide to enhance the growth rate of human endothelial cells (HUVEC) on the
      surface. To graft cell-adhesive peptide RGD on the PCL surface, the PCL surface
      was first etched by the selected solvent with only nanometer-scale of surface
      disturbance, and simultaneously embedded with DSPE-PEG [di-stearoyl-phosphatidyl
      ethanolamine-methoxy-poly (ethylene glycol)] moiety. Then the PCL-PEG surface was
      photochemically grafted by GRGD to form PCL-PEG-RGD surface. PCL and the modified
      surfaces were characterized by surface morphology, surface disturbance, contact
      angles, ATR-FTIR functional group analysis, and the growth rate of HUVEC. The
      surface disturbances of PCL and the modified surfaces were examined by atomic
      force microscope (AFM) and presented by the topography and a roughness parameter,
      Ra. The Ra values were 16.4 +/- 3.0, 34.8 +/- 1.6, and 12.8 +/- 0.3 nm (n = 3)
      for PCL, PCL-PEG, and PCL-PEG-RGD surfaces, respectively. The topographies of the
      surfaces and Ra values indicated that the PCL modified technique developed by
      this study resulted in only nanometer scale of surface disturbance. In addition
      to reducing surface disturbances, reducing contact angle from 73.7 degrees +/-
      0.4 (n = 3) for the PCL surface to 56.9 degrees +/- 4.0 (n = 3) for the PCL-PEG
      surface, and the ATR-FTIR transmission spectra at 1660 cm(-1) for shoulder of
      amine I of PCL-PEG-RGD surface both confirmed the successful modification of PCL
      surfaces. HUVECs adhered well and grew on the PCL-PEG-RGD surface after 36 h
      incubation, whereas other surfaces did not support growth. Moreover, the
      viability for the relative growth rate of HUVECs on the PCL-PEG-RGD surface
      analyzed by MTT assay showed 8.5 times greater growth than that of the unmodified
      one. In conclusion, a PCL-PEG-RGD surface for enhancing the growth rate of HUVECs
      has been prepared by a new technique that caused only a nanometer-scale of
      surface disturbance. This technique and the PCL-PEG-RGD surface could be further
      applied to engineer soft tissues.

PMID- 15578648
TI  - Trisomy 8 mosaicism in a patient with heterotaxia.
AB  - Constitutional trisomy 8 mosaicism (CT8M) is a relatively rare trisomy in humans
      with a characteristic phenotype. We report an infant with the characteristic CT8M
      phenotype in addition to heterotaxia. A number of chromosomal abnormalities have
      been reported in association with laterality defects but this is the first time
      heterotaxia is reported in CT8M. In addition to expanding CT8M phenotype, our
      report may provide insight into the mechanism of heterotaxia.

PMID- 15578649
TI  - Late or emergency (salvage) cerclage of a dilated cervix after tissue support
      with Pelvicol implant: a case.
AB  - Our objective was to evaluate the effectiveness of a late or emergency (salvage)
      cerclage after tissue reinforcement with Pelvicol natural implant, in preventing
      premature rupture of the fetal membranes and advancing pregnancy prolongation. A
      flat sheet of Pelvicol, a sterile acellular natural (porcine) implant was used in
      an emergency cerclage to reinforce the thin tissues of a widely dilated cervix in
      a 24 weeks' twin gestation with prolapsed unruptured membranes, without
      contractions, placental abruption, or intrauterine infection. The gestation was
      extended to 38 weeks without any complications. Two live healthy newborns were
      delivered by elective cesarean section due to a nonvertex/vertex presentation.
      The implant was found to be attached almost unaltered firmly on the outer surface
      of the membrane sac just opposite to the internal os. It seems that Pelvicol is
      safe and apparently protects by clothing the thinned, soft, and weak wall of a
      significantly dilated uterine cervix and the bulging or protruding gestational
      membranes. It also reinforces and strengthens the tissue thickness and
      resistance, rendering more accurate and safe the otherwise delicate and risky
      late cerclage. The technique gives hopes that it can help in pregnancy
      prolongation.

PMID- 15578650
TI  - In vitro evaluation of antibiotic release from and bacteria growth inhibition by
      antibiotic-loaded acrylic bone cement spacers.
AB  - The antibiotic release from and the bacteria growth inhibition by antibiotic
      loaded acrylic bone cement hip spacers were studied. The cement used was Palacos
      R, and it was loaded with either one antibiotic powder (gentamicin, vancomycin,
      teicoplanin, or synercid) [monoantibiotic case] or two antibiotic powders
      (gentamicin + vancomycin or gentamicin + teicoplanin) [biantibiotic case] and
      then tested against Staphylococcus epidermidis, Staphylococcus aureus,
      Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA).
      Antibiotic elution and bacteria growth were measured every 24 h simultaneously by
      fluorescence polarization immunoassay and photometrically, respectively. The
      gentamicin + vancomycin combination achieved the longest growth inhibition on S.
      epidermidis and MRSA (mean of 20 and 14 days, respectively). Gentamicin +
      teicoplanin-loaded spacers were capable of inhibiting growth on E. faecalis and
      S. aureus for the longest period (11 and 16 days, respectively). The highest
      concentrations of gentamicin and vancomycin could be assayed during the first 4
      days. Teicoplanin concentrations could be detected only during the first 72 h,
      synercid was not detected at all, possibly because of the limitation of the
      detection technique used. A greater percentage of the gentamicin was released
      than of the vancomycin. The aminoglycosid-glycopeptid combination showed a
      synergistic effect on the release of gentamicin, but not on vancomycin or
      teicoplanin. Biantibiotic-impregnated hip spacers proved to be superior to
      monoantibiotic ones. Because of important differences between the conditions used
      for the present tests and the in vivo environment, any recommendation with regard
      to the use of monoantibiotic- and biantibiotic-loaded acrylic bone cement spacers
      must await the results of further investigations.

PMID- 15578652
TI  - Bioartificial liver in acute liver failure: impostor or simply misunderstood?

PMID- 15578651
TI  - Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic
      arch anomalies in the offspring of diabetic rats.
AB  - BACKGROUND: Maternal diabetes (MD) is a risk factor for offspring to develop
      cardiovascular anomalies; this is of growing clinical concern since the number of
      women in childbearing age with compromised glucose homeostasis is increasing.
      Hyperglycemia abrogates cardiovascular development in vitro; however, a link to
      cardiovascular defects in diabetic offspring remains to be investigated. METHODS:
      We have studied cardiovascular development in offspring of MD rats by examining
      serial histological sections of GD 12.0-18.0 offspring. Development of pharyngeal
      arch artery malformations was analyzed and related to intracardiac anomalies.
      RESULTS: Pharyngeal arch artery and intracardiac defects were present in 27 of 37
      MD GD 13.0-18.0 offspring. Early sixth arch arteries showed abrogated
      arteriogenesis, whereas fourth arch artery defects developed as a result of
      abnormal remodeling. Morphometrical analysis showed increased apoptosis in
      regressing artery segments and reduced apoptosis in persisting artery segments.
      Double outlet right ventricle with infundibular stenosis (tetralogy of Fallot)
      was predominantly found in combination with sixth artery defects and pulmonary
      atresia. As confirmed by morphometric analysis and three-dimensional (3D)
      reconstructions, outflow tract defects coincided with endocardial cushion
      hypoplasia. Cases with teratology of Fallot additionally showed a shorter outflow
      tract. No relation with apoptosis or disturbed neural crest cell migration was
      found. CONCLUSIONS: Our data uniquely demonstrate mechanistic differences
      involved in the development of sixth and fourth artery anomalies. Whereas
      increased apoptosis induces fourth artery anomalies, pulmonary outflow
      obstruction abrogates sixth artery differentiation independent of apoptosis. The
      model presented allows analysis of diabetic conditions on cardiovascular
      development in vivo, essential for elucidating this teratology.

PMID- 15578653
TI  - Laminin-apatite composite coating to enhance cell adhesion to ethylene-vinyl
      alcohol copolymer.
AB  - A laminin-apatite composite layer with enhanced cell adhesive properties was
      successfully formed on the surface of an ethylene-vinyl alcohol copolymer (EVOH)
      by a liquid phase coating process. The coating process was carried out with the
      following procedure. First, an EVOH plate was alternately dipped in 200 mM
      calcium and 200 mM phosphate solutions to introduce nuclei or precursors of
      apatite to its surface. Second, the surface-modified EVOH was immersed in a
      calcium phosphate solution, which was supersaturated with respect to apatite and
      containing laminin. As a result of this procedure, a laminin-apatite composite
      layer with a thickness of 2.5-3.0 microm was formed on the EVOH surface.
      Epithelial-like cells (BSCC93) adhered to the laminin-apatite composite layer
      showed enhanced cell spreading, which was due to the biological effect of
      laminin. The number of cells adhered to the laminin-apatite composite layer on
      EVOH was approximately 10 times as large as that adhered to the surface of the
      untreated, laminin-adsorbed, or apatite-coated EVOH. Therefore, this type of
      composite material consisting of a synthetic polymer, apatite, and laminin has
      great potential as a skin terminal, with improved adhesiveness to skin tissue, as
      well as good biocompatibility.

PMID- 15578654
TI  - In vivo analysis of oligodendrocyte lineage development in postnatal FGF2 null
      mice.
AB  - Analysis of fibroblast growth factor 2 null (FGF2-/-) and wild-type (FGF2+/+)
      mice was used to interpret the potential in vivo role of endogenous FGF2 on
      oligodendrocyte lineage cell (OLC) responses during oligodendrogenesis and
      myelination. In wild-type mouse spinal cord, FGF2 levels increased approximately
      threefold between the first and second postnatal weeks, a period corresponding
      with the peak of oligodendrogenesis. Absence of this developmental FGF2 elevation
      in FGF2-/- mice eliminated the transient overproduction of oligodendrocytes that
      is known to occur at the peak of oligodendrogenesis in wild-type mice. Absence of
      FGF2 did not affect oligodendrocyte progenitor (OP) density or proliferation,
      based on BrdU incorporation, and also did not alter survival, based on TUNEL
      analysis. To examine OLC differentiation in vivo, retrovirus encoding-enhanced
      green fluorescent protein (GFP) was injected into the spinal cord to heritably
      label endogenous cycling cells in the white matter at postnatal day 7 and then
      identify the generated cells at postnatal day 28. Phenotypes of cells expressing
      GFP were identified by morphology and immunolabeling, using CC1 for
      oligodendrocytes and NG2 combined with platelet-derived growth factor alpha
      receptor for OPs. Within the population of GFP-labeled cells, the proportion of
      oligodendrocytes was higher in FGF2-/- mice, indicating that endogenous FGF2
      inhibited OLC differentiation in wild-type mice. Furthermore, in FGF2-/- mice
      fewer cells appeared to be generated from an initial retrovirus-labeled cell,
      consistent with more frequent differentiation into post-mitotic oligodendrocytes.
      This in vivo analysis demonstrates that the predominant role of endogenous FGF2
      on OLCs in development is inhibition of differentiation.

PMID- 15578655
TI  - Phase II study of high-dose fish oil capsules for patients with cancer-related
      cachexia: a Cancer and Leukemia Group B study.

PMID- 15578656
TI  - Glial glutamate transporter expression patterns in brains from multiple mammalian
      species.
AB  - It is generally assumed that rodent brains can be used as representative models
      of neurochemical function in other species, such as humans. We have compared the
      distributions of the predominant glial glutamate transporters in rodents,
      rabbits, cats, pigs, monkeys, and humans. We identify similarities but also
      significant differences between species. GLT-1v, which is abundantly expressed by
      rodent astrocytes, is expressed only in a rare subset of astrocytes of cats and
      humans, and appears to be absent from brains of rabbits and monkeys. Conversely,
      in the pig brain GLT-1v is expressed only by oligodendrocytes. GLAST and GLT
      1alpha expression differed significantly between species; while rodents and
      rabbits exhibited uniform expression patterns in cortex, higher species,
      including cats, pigs, monkeys, and humans, exhibited heterogeneities in cortical
      and hippocampal expression. Patches devoid of labeling intermingling with patches
      of strong labeling were evident in areas such as temporal cortex and frontal
      cortex. In addition, we noted that in human motor cortex, there were
      inconsistencies in labeling for the C-terminal of GLT-1alpha and common domains
      of GLT-1, suggesting that the C-terminal region may be missing or that an
      unidentified splicing is present in many human astrocytes. Collectively our data
      suggest that assumptions as to the roles of glutamate transporters in any species
      may need to be tested empirically.

PMID- 15578657
TI  - Constitutive nuclear localization of activated caspase 3 in subpopulations of the
      astroglial family of cells.
AB  - In a study examining for apoptosis in spontaneously hypertensive rats (SHR), we
      observed the constitutive presence of activated caspase 3 in Bergmann glia. We
      then examined stroke-prone SHR as well as the normotensive strains Wistar, Wistar
      Kyoto, and Sprague-Dawley. In all these strains, we found that Bergmann glia
      expressed activated caspase 3 in nuclei. Furthermore, subpopulations of
      astrocytes in the granular layer of the cerebellar cortex, in the hippocampus,
      and spinal cord gray matter, particularly in the dorsal part of the dorsal horns,
      expressed nuclear activated caspase 3. This distribution corresponds to the
      distribution of astrocytes that express the glutamate transporter GLAST. We
      conclude that Bergmann glia and a subpopulation of astrocytes throughout the CNS
      express activated caspase 3 in nuclei to fulfill a yet-to-be defined non
      apoptotic function. GLIA.

PMID- 15578659
TI  - ATP binding cassette transporter ABC1 is required for the release of interleukin
      1beta by P2X7-stimulated and lipopolysaccharide-primed mouse Schwann cells.
AB  - Schwann cells are best known as myelinating glial cells of the peripheral nervous
      system, but they also participate actively in the sphere of immunity by producing
      pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta). In a previous
      study, we demonstrated that posttranslational processing of IL-1beta by immune
      challenged Schwann cells required the P2X7 receptor. Remarkably, the release of
      IL-1beta was not associated with cell death, indicating the involvement of an
      active mechanism. ATP binding cassette (ABC) transporters are known to transport
      leaderless secretory proteins, such as IL-1beta; therefore, we investigated
      whether such transporters were at work in Schwann cells. Mouse Schwann cells
      expressed ABC1 transporter mRNA and displayed the functional protein.
      Glybenclamide and diisothiocyanato-stilbene-disulfonic acid (DIDS), two blockers
      of chloride fluxes that drive the export activity of ABC1 transporters, inhibited
      IL-1beta release without altering its intracellular processing. Enhancing
      chloride efflux potentiated the release of IL-1beta, while decreasing it led to a
      strong reduction in its release. Because the stimulation of the P2X7 receptor
      also activates a chloride conductance, we investigated the possibility of a sole
      anionic pathway mobilized by the P2X7 receptor and ABC1. Glybenclamide and DIDS
      had no significant effects on the P2X7-activated chloride current suggesting
      therefore the existence of two different pathways. In summary, ABC1 transporters
      are required for the release of IL-1beta by mouse Schwann cells. Being associated
      together with chloride conductance, P2X7 receptors and ABC1 transporters
      delineate a subtle and complex regulation of IL-1beta production in mammalian
      Schwann cells. Furthermore, ABC1 transporters could be a target of therapeutic
      interest for regulating IL-1beta activity in neuroinflammation disorders.

PMID- 15578658
TI  - HIV-1 tat protein induces a migratory phenotype in human fetal microglia by a
      CCL2 (MCP-1)-dependent mechanism: possible role in NeuroAIDS.
AB  - Acquired immune deficiency syndrome (AIDS) encephalitis and dementia are
      characterized by neuronal loss, astrogliosis, and microglia activation and
      migration that contribute to the formation of multinucleated giant cells. Despite
      extensive evidence of pathological changes in the brain of infected individuals,
      the mechanisms of human immune deficiency virus type 1 (HIV-1) entry, microglia
      migration, and viral propagation within the brain are still not completely
      understood. In this study, we report that the induction of a migratory phenotype
      in human fetal microglia by the HIV-1 transactivator protein, tat, is mediated by
      the chemokine, CCL2. CCL2 or tat treatment alone induced rearrangement of actin
      and the formation of microglial processes. The time course of cell membrane
      ruffling induced by CCL2 was faster (5-30 min) than that elicited by tat
      treatment (2-3 h). Our previous data in human fetal microglia showed that tat
      induces CCL2 expression. Thus, we examined whether tat-induced microglia membrane
      ruffling and process formation, critical components in cell migration, are
      mediated by the secretion of CCL2 by these cells. To test this hypothesis, we
      treated microglia with tat protein in the presence of neutralizing CCL2
      antibodies. Co-treatment with neutralizing CCL2 antibodies resulted in the loss
      of tat-induced membrane ruffling. Tat treatment of microglia induced polarization
      of CCR2, the receptor for CCL2, to the leading edge of processes, further
      suggesting a CCL2-dependent mechanism of tat-induced microglia migration. Our
      data indicate that tat facilitates microglia migration by inducing autocrine CCL2
      release. Our results suggest that tat induced CCL2 secretion may be one of the
      early signals during NeuroAIDS.

PMID- 15578660
TI  - Sequence of oligodendrocyte development in the human fetal telencephalon.
AB  - Oligodendrocytes (OL), cells that myelinate axons in the CNS, differentiate from
      early to late oligodendrocyte progenitor cells (OPC) to become mature OL. Unlike
      the case in the rodent brain, myelin formation starts prenatally in the human
      brain, but the sequence of OL development and the onset of myelination are not
      well understood. We studied the human fetal forebrain at midgestation (17-23
      gestational weeks, g.w.) using OL lineage-specific antibodies and mRNA probes.
      Early OPC were present in a gradient from the subventricular zone to the cortical
      plate. Their close apposition to radial glia fibers suggests a possible role of
      these fibers in OPC migration. Late OPC reached peak density in the subplate
      layer, whereas multipolar cells with the morphology of mature OL were restricted
      to the emerging white matter. At 20 g.w., myelinated axons were observed in the
      diencephalon, but not in the telencephalon, consistent with caudal-to-rostral
      progression of myelination. Interestingly, in organotypic slice cultures of the
      same gestational ages, the subventricular zone contained a considerably greater
      number of the mature OL cells, suggesting the presence of inhibitory signals in
      vivo. Overall, in addition to considerable similarities with rodents, important
      differences in temporal and spatial distribution and regulatory signals for OL
      differentiation exist in the human brain.

PMID- 15578661
TI  - Dystroglycan is involved in laminin-1-stimulated motility of Muller glial cells:
      combined velocity and directionality analysis.
AB  - We investigate the role of dystroglycan, a major laminin-1 receptor and central
      member of the dystrophin-glycoprotein complex, in the laminin-1 induced motility
      of cultured Muller glial cells. Binding of laminin-1 to dystroglycan was
      prevented by IIH6, a function-blocking monoclonal antibody against alpha
      dystroglycan. As an alternative means of inhibition, we used heparin to mask the
      dystroglycan binding site of the laminin-1, known to overlap with heparin binding
      sites. Cell motility was characterized in a two-dimensional motility assay based
      on computer-controlled videomicroscopy and statistical analysis of cellular
      trajectories. We obtained data on both the cell velocity and the diffusion index,
      a measure of direction-changing frequency. Both means of inhibition of
      dystroglycan function led to a significant decrease in the ability of laminin-1
      to stimulate cell migration. At the same time, dystroglycan function does not
      appear to be involved in laminin-1-dependent increase in process dynamism and
      direction-changing activity.

PMID- 15578662
TI  - Integrin-growth factor interactions as regulators of oligodendroglial development
      and function.
AB  - Central nervous system (CNS) development requires mechanisms for the regulation
      of cell number. Although growth factors are essential determinants of the
      proliferation and apoptosis that determine final numbers, the long-range nature
      of signals from diffusible growth factors makes them insufficient for the
      provision of the precise and localized signals required. Integration of integrin
      and growth factor receptor signaling in controlling cell behavior has been an
      important theme of research over the past several years. The focus of this review
      is on the mechanisms by which integrin-growth factor interactions regulate the
      development of oligodendrocytes and provide a mechanism for controlling, both in
      space and in time, oligodendrocyte numbers in the developing CNS.

PMID- 15578663
TI  - Receptor rigidity and ligand mobility in trypsin-ligand complexes.
AB  - The trypsin-like serine proteases comprise a structurally similar family of
      proteins with a wide diversity of biological functions. Members of this family
      play roles in digestion, hemostasis, immune responses, and cancer metastasis.
      Bovine trypsin is an archetypical member of this family that has been extensively
      characterized both functionally and structurally, and that preferentially
      hydrolyzes Arg/Lys-Xaa peptide bonds. We have used molecular dynamics (MD)
      simulations to study bovine trypsin complexed with the two noncovalent small
      molecule ligands, benzamidine and tranylcypromine, that have the same hydrogen
      bond donating moieties as Arg and Lys side-chains, respectively. Multiple (10)
      simulations ranging from 1 ns to 2.2 ns, with explicit water molecules and
      periodic boundary conditions, were performed. The simulations reveal that the
      trypsin binding pocket residues are relatively rigid regardless of whether there
      is no ligand, a high-affinity ligand (benzamidine), or a low-affinity ligand
      (tranylcypromine). The thermal average of the conformations sampled by
      benzamidine bound to trypsin is planar and consistent with the planar internal
      geometry of the benzamidine crystallographic model coordinates. However, the most
      probable bound benzamidine conformations are +/-25 degrees out of plane, implying
      that the observed X-ray electron density represents an average of densities from
      two mirror symmetric, nonplanar conformations. Solvated benzamidine has free
      energy minima at +/-45 degrees , and the induction of a more planar geometry upon
      binding is associated with approximately 1 kcal/mol of intramolecular strain.
      Tranylcypromine's hydrogen-bonding pattern in the MD differs substantially from
      that inferred from the X-ray electron density. Early in simulations of this
      system, tranylcypromine adopts an alternative binding conformation, changing from
      the crystallographic conformation, with a direct hydrogen bond between its amino
      moiety and the backbone oxygen of Gly219, to one having a bridging water
      molecule. This result is consistently seen with the CHARMM22, Amber, or OPLS-AA
      force fields. The trypsin-tranylcypromine hydrogen-bonding pattern observed in
      the simulations also occurs as the crystallographic binding mode of the Lys15
      side-chain of bovine pancreatic trypsin inhibitor bound to trypsin. In this
      latter cocrystal, a bridging crystallographic water does reside between the side
      chain's amino group and the trypsin Gly219 backbone oxygen. Furthermore, the
      trypsin-tranylcypromine simulations sample two different stable
      noncrystallographic binding poses. These data suggest that some of the electron
      density ascribed to tranylcypromine in the X-ray model is rather due to a bound
      water molecule, and that multiple tranylcypromine binding conformations
      (crystallographic disorder) may be the cause of ambiguous electron density. The
      combined trypsin-benzamidine and trypsin- tranylcypromine results highlight the
      ability of simulations to augment protein-ligand complex structural data by
      deconvoluting the effects of thermal and structural averaging, and by finding
      energetically optimal ligand and bound water positions for weakly bound ligands.

PMID- 15578664
TI  - Psychiatric issues in retrospective challenges of testamentary capacity.
AB  - BACKGROUND: Challenges to Wills on the basis of lack of testamentary capacity are
      likely to increase due to a combination of economic factors, high prevalence of
      mental disorders in old age and the complexity of many modern families. Geriatric
      psychiatrists and other experts will be asked to provide expert assessment of the
      testamentary capacity of individuals whose Wills are being challenged
      retrospectively. The traditional criteria described in the Banks vs Goodfellow
      case have been held as the standard for testamentary capacity. However, these
      criteria may not be comprehensive enough for the coming generation of expert
      assessors. METHOD: The literature and selected international case law relevant to
      testamentary capacity were reviewed. Particular focus is placed on the conceptual
      and empirical approaches to the assessment of complex capacities that may inform
      the development of specific legal standards. In addition, 25 consecutive medico
      legal reports on retrospective testamentary capacity were analyzed according to
      co-morbid medical and psychiatric disorders as well as psychosocial and
      behavioural variables. Illustrative case vignettes are included. RESULTS: The
      typical profile for retrospective challenges to testamentary capacity included a
      radical change from a previous Will (72%), where undue influence was alleged
      (56%), in a testator with no biological children (52%), who executed the Will
      less than a year prior to death (48%). Co-morbid conditions were dementia (40%),
      alcohol abuse (28%) and other neurological/psychiatric conditions (28%).
      CONCLUSIONS: While Banks vs Goodfellow continues to provide a sound basis for
      assessing testamentary (task-specific) capacity, the complexity and subtlety of
      the issues reflected in these cases highlight the need to go beyond the
      traditional criteria and assess situation-specific factors. Expert assessors need
      to determine whether the testator appreciated the consequences of executing or
      changing a Will, especially when there has been a radical change in the context
      of a complex or conflictual family environment. Empirical studies addressing the
      cognitive functions relevant to testamentary capacity and the development of
      legal standards based on a competency construct may also help to inform
      retrospective capacity assessments.

PMID- 15578665
TI  - Blood transfusions in children with cancer and hematologic disorders: why, when,
      and how?

PMID- 15578666
TI  - Prevalence and correlates of depression in Chinese oldest-old.
AB  - BACKGROUND: In Hong Kong, the aged population will be increased rapidly in the
      coming three decades and the oldest-old (aged 80 and above) is the fastest
      growing age group. In this paper, we examined the prevalence rate and the
      correlates of depression for the oldest-old. METHOD: This article analyzes cross
      sectional data collected from a representative community sample of 1 903 Chinese
      elderly people aged 60 or above in Hong Kong. Respondents were interviewed in
      face-to-face format with structural questionnaire. RESULT: Using 8 as the cut-off
      point for the 15-item Geriatric Depression Scale, we found that the prevalence
      rate was greater for the oldest-old (31.1% +/- 9.7%) than for the young-old (aged
      between 60 and 69; 19.1% +/- 2.8%) and the old-old (aged 70 and 79; 22.4% +/-
      4.2%) groups. Logistic regression analyses revealed that financial strain, poor
      self-rated health, loneliness, and heart disease were significantly and
      positively related to depression in the oldest-old after gender, marital status,
      education, living arrangement, functional disability, sensory impairment,
      cognitive ability, and the presence of eight medical conditions were controlled.
      Interestingly, financial strain, self-rated health, and loneliness were found to
      be significant correlates of depression in the young-old and the old-old groups,
      too. CONCLUSION: Depression is a serious problem for the oldest-old but a number
      of correlates are consistently identified in the oldest-old, as well as the two
      other age groups in the elderly population. Therefore, aged care service
      practitioners must take these correlates into consideration in their prevention
      and treatment for depression for all different age groups in the aged.

PMID- 15578667
TI  - The effects of reminiscence on depressive symptoms and mood status of older
      institutionalized adults in Taiwan.
AB  - OBJECTIVE: This study examined the effects of reminiscence on depressive symptoms
      and mood status of elderly people residing in long-term care facilities. METHODS:
      A longitudinal quasi-experimental design was conducted, using two equivalent
      groups for pre-post test and purposive sampling. Each subject was administered
      pre- and post- tests at a 4 month interval, but subjects in the experimental
      group underwent weekly individual reminiscence therapy. Geriatric Depression
      Scale short form (GDS-SF) and Apparent Emotion Rating Scale (AER) were used as
      study instruments. RESULTS: Forty-eight subjects completed the study, with 25 in
      the experimental group and 23 in the control group. The experimental findings
      indicated that the experimental group demonstrated fewer depressive symptoms (p <
      0.05) and better mood status (p = 0.05) on the post-test comparing to the control
      group. CONCLUSION: These warranted that reminiscence therapy is a recommended
      therapy for older people who reside in care facilities. It can provide a basis
      for planning geriatric care in community to promote the well being and quality of
      life of older people.

PMID- 15578668
TI  - Comparison of suicide in people aged 65-74 and 75+ by gender in England and Wales
      and the major Western countries 1979-1999.
AB  - BACKGROUND: The factors most strongly associated with suicide are age and gender-
      more men than women, and, more people over 65 kill themselves. As a number of
      Governments have targets to reduce suicide levels we compare elderly suicide
      rates over a 20-year period in England and Wales. And the major Western countries
      focusing upon age and gender. METHOD: WHO mortality data were used to calculate
      three-year average General Population Suicide Rates (GPSR) for 1979-1981 to 1997
      1999 and rates of people aged 65-74 and 75+ suicide by gender to provide ratios
      of change and a statistical comparison of England and Wales and the Major Western
      countries over the period. RESULTS: Male GSPR: '65-74' suicide ratios fell
      significantly in six countries and in three for the '75+'. Female GSPR: '65-74'
      suicide ratios fell in every country except Spain. Proportionately, there were
      more suicides in the over 65s in countries with an 'extended family' tradition,
      Spain, Italy, Germany, France and Japan, than in the five 'secular' countries.
      England and Wales male '65-74' suicide fell significantly more than Canada,
      France, Germany, Italy, Japan, Spain, Netherlands and the USA, and did
      significantly better than the other countries for all female senior citizen
      suicides. CONCLUSION: Suicide of the over-65s has improved in seven countries,
      especially in England and Wales, who had the greatest proportional reduction,
      which reflects well upon the psycho-geriatric and community services. However, in
      all countries, male 65-74 rates did not match the female out so extra efforts are
      needed to improve male rates.

PMID- 15578669
TI  - The applicability and the inter-rater reliability of the Comprehensive
      Psychopathological Rating Scale in an elderly clinical population.
AB  - BACKGROUND: Psychopathological rating scales are developed and tested on a
      relatively young population. Their applicability and psychometric performance in
      the elderly (aged above 60-65 years) are mostly unknown. It is unknown how
      factors related to ageing or mild cognitive dysfunction influence the
      applicability and the reliability of these scales. We tested the applicability
      and the inter-rater reliability of the Dutch version of the Comprehensive
      Psychopathological Rating Scale (CPRS) on an elderly (age > 60 years) inpatient
      population. METHODS: The applicability and reliability (expressed by differently
      weighted Kappa coefficients) of the CPRS was assessed by investigating 62
      consecutively referred patients in a ward for elderly patients with acute
      psychiatric problems that were primarily functional in nature. The results are
      compared with those found in a younger population. RESULTS: The applicability and
      reliability of the CPRS on the elderly can be categorised as sufficient to good
      and is comparable with results for a younger population. We did not find any
      specific factors influencing the practicality, or the reliability of the CPRS
      when applied to an elderly group of people with a mild cognitive dysfunction.
      CONCLUSIONS: The CPRS does not loose its clinical relevance with age, as the
      applicability and the reliability of the CPRS is not influenced by ageing or mild
      cognitive dysfunction. The CPRS can detect a broad range of symptoms and due to
      its psychometric properties it is a useful instrument for measuring an elderly or
      young population.

PMID- 15578670
TI  - Is vascular depression a distinct sub-type of depressive disorder? A review of
      causal evidence.
AB  - BACKGROUND: Vascular depression is an important conceptual and clinical concept.
      OBJECTIVE: To apply criteria which, in an ideal world, should be satisfied before
      an association between depression and vascular disease can be considered robust.
      METHOD: A literature review with discussion of findings in the light of recently
      suggested guidelines for the development of new psychiatric disorders. RESULTS:
      There is considerable evidence linking depression in later life with vascular
      brain disease but the interaction is bi-directional. Depression and vascular
      disease could be mediated by factors other than traditional vascular risk
      factors. There is increasing interest in mechanisms such as inflammatory
      processes which may mediate both depression and vascular disease. CONCLUSIONS:
      Vascular depression provides a useful framework with which to remind the
      clinician of important interactions between depression and vascular disease but
      conceptually it may be too restrictive.

PMID- 15578671
TI  - Cerebral emboli and paradoxical embolisation in dementia: a pilot study.
AB  - BACKGROUND: The causes of the common dementias remain unknown. Paradoxical
      embolisation of the cerebral circulation by venous thrombi passing through venous
      to arterial shunts (v-aCS) in the heart or pulmonary circulation is known to
      occur in cryptogenic stroke and post-operative confusion following hip
      replacement. OBJECTIVES: To explore the role of paradoxical embolisation in
      dementia by investigating for cerebral emboli, venous to arterial circulation
      shunt (v-aCS) and carotid artery disease. METHODS: Forty-one patients with
      dementia (24 Alzheimer's AD and 17 vascular VaD) diagnosed using DSM-IV criteria
      and 16 controls underwent transcranial Doppler (TCD) detection of spontaneous
      cerebral emboli in both middle cerebral arteries. A v-aCS was detected by
      intravenous injection of an air/saline ultrasound contrast at rest and after
      provocation by coughing and Valsalva's manoeuvre. Carotid artery disease was
      assessed by duplex imaging. RESULTS: Cerebral emboli were detected in 11 (27.5%)
      dementia patients compared with one (7%) control (p = 0.15) with emboli being
      most frequent in VaD (41%) compared to controls [OR (95% CI): 10.5 (1.1, 98.9), p
      = 0.04]. A v-aCS was detected in 25 (61%) patients and seven (44%) controls (p =
      0.24). In dementia patients with cerebral emboli; v-aCS was detected in seven
      (64%) and moderate to severe carotid stenosis was present in three (30%).
      CONCLUSION: Cerebral emboli and v-aCS may be more frequent in patients with both
      VaD and AD than in controls, which suggest paradoxical embolisation as a
      potential mechanism for cerebral damage. This pilot study justifies a definitive
      case-control study.

PMID- 15578672
TI  - Is there a case for a specialist forensic psychiatry service for the elderly?
AB  - BACKGROUND: The number of elderly offenders in England and Wales is increasing.
      There is, therefore, a concern that their needs may not be met by existing
      forensic services. However, there is a paucity of information on elderly patients
      referred to existing forensic psychiatric units. METHOD: Data on patients over
      the age of 65 years referred to a large medium secure forensic psychiatric unit
      in London were collected for a 13-year period using a retrospective design. The
      sample was divided into those who had first offended before the age of 65 and
      those who had offended after the age of 65. Data was also collected on victims of
      the offences. RESULTS: 5477 referrals were made during the study period. Those
      aged over 65 years accounted for 78 (1.4%) of all referrals. These 78 referrals
      were for 55 patients. Forty-five of these had offended. Case notes of 42 patients
      from this group were screened. Sexual and violent offences accounted respectively
      for 20 (47%) and 15 (36%) of offences. 31% had no psychiatric disorder but
      organic disorders accounted for 21% of cases. Only eight (19%) required admission
      to the medium secure unit. Fourteen (33%) had first offended after the age of 65
      while others were known to either the forensic services or criminal justice
      system before the age of 65. The two groups did not differ from each other.
      CONCLUSIONS: The elderly accounted for very few referrals to the medium secure
      forensic service, yet there is a high prevalence of psychiatric morbidity in both
      remand and sentenced elderly prisoners. Therefore, elderly offenders with
      psychiatric morbidity may benefit from specialist old age psychiatric forensic
      services, perhaps at a supraregional level.

PMID- 15578673
TI  - The Middelheim Frontality Score: a behavioural assessment scale that
      discriminates frontotemporal dementia from Alzheimer's disease.
AB  - BACKGROUND: Despite striking neuropsychological and behavioural differences
      between Alzheimer's disease (AD) and frontotemporal dementia (FTD), clinical
      diagnostic criteria failed to discriminate FTD from AD patients. We therefore
      developed the Middelheim Frontality Score (MFS), a disease-long clinical and
      behavioural assessment tool that measures frontal lobe features, and set up this
      prospective study in clinically diagnosed AD and FTD patients to assess
      discriminatory power and intra- and inter-rater variability. METHODS: Patients
      with probable AD (n = 400) and FTD (n = 62) were included. The MFS was obtained
      by summating the scores obtained in a standardized fashion on ten items yielding
      a total maximal score of 10. Information was obtained through an interview of the
      patient and her/his caregiver, clinical files and behavioural observation.
      RESULTS: Comparing mean total MFS scores, FTD patients (6.3 +/- 1.8) had
      significantly higher scores than AD patients (3.1 +/- 1.8) (p < 0.001).
      Distribution of scores on individual MFS items was significantly different
      between both disease groups (chi(2) = 76.2; p < 0.001). A moderately positive and
      highly significant correlation was shown between the total MFS score and
      diagnosis FTD (r = 0.478; p < 0.0001). Applying a total MFS score of 5 as
      discriminatory cut-off, a specificity of 89.0% and a sensitivity of 88.7% were
      achieved. Intra- and inter-rater variability was calculated in a different study
      population by means of retest correlation, revealing moderate to strong positive
      correlations of high statistical significance. CONCLUSIONS: The MFS is a clinical
      and behavioural assessment scale that measures frontal lobe features and that was
      shown to reliably discriminate FTD from AD patients.

PMID- 15578674
TI  - Statistical evaluation of time-dependent metabolite concentrations: estimation of
      post-mortem intervals based on in situ 1H-MRS of the brain.
AB  - Knowledge of the time interval from death (post-mortem interval, PMI) has an
      enormous legal, criminological and psychological impact. Aiming to find an
      objective method for the determination of PMIs in forensic medicine, 1H-MR
      spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain
      metabolite concentrations after death. Following the characterization of newly
      observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full
      set of acquired spectra was analyzed statistically to provide a quantitative
      estimation of PMIs with their respective confidence limits. In a first step,
      analytical mathematical functions are proposed to describe the time courses of 10
      metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the
      inverted functions are used to predict PMIs based on the measured metabolite
      concentrations. Individual PMIs calculated from five different metabolites are
      then pooled, being weighted by their inverse variances. The predicted PMIs from
      all individual examinations in the sheep model are compared with known true
      times. In addition, four human cases with forensically estimated PMIs are
      compared with predictions based on single in situ MRS measurements.
      Interpretation of the individual sheep examinations gave a good correlation up to
      250 h post-mortem, demonstrating that the predicted PMIs are consistent with the
      data used to generate the model. Comparison of the estimated PMIs with the
      forensically determined PMIs in the four human cases shows an adequate
      correlation. Current PMI estimations based on forensic methods typically suffer
      from uncertainties in the order of days to weeks without mathematically defined
      confidence information. In turn, a single 1H-MRS measurement of brain tissue in
      situ results in PMIs with defined and favorable confidence intervals in the range
      of hours, thus offering a quantitative and objective method for the determination
      of PMIs.

PMID- 15578675
TI  - Mortality in Alzheimer's disease: a comparative prospective Korean study in the
      community and nursing homes.
AB  - OBJECTIVE: To test a hypothesis that Alzheimer's disease (AD) patients in nursing
      homes have higher mortality rate than do AD patients cared for at home and to
      investigate the predictors of mortality in AD. DESIGN: A one-year prospective
      follow-up in Korea. METHODS: A total of 252 subjects (107 in the community, 145
      in a nursing home) were longitudinally assessed at baseline, 6 months and 12
      months. Mortality rates between groups were compared using Kaplan-Meier curve and
      log-rank statistics. Relative risks (RRs) were examined by the Cox proportional
      hazards model. RESULTS: Overall one-year mortality rate in AD was 18.7%. There
      was no statistically significant difference in AD mortality rates between
      patients who continued to be cared for at home and AD patients in the nursing
      home. After controlling for age, group (nursing home or community), severity of
      dementia, Mini-Mental State Examination (MMSE) score and vascular risk factors,
      there remained advanced age [risk ratio (RR) 1.06; 95% confidence interval (CI)
      1.04-1.09], advanced Global Deterioration Scale (GDS) stage (RR 1.98; 95% CI 1.41
      2.77), longer duration of AD (RR 1.07; 95% CI 1.04-1.10), presence of tactile
      hallucination (RR 1.74; 95% CI 1.08-2.78), wandering (RR 1.89; 95% CI 1.18-3.02)
      and depression (RR 1.07; 95% CI 1.02-1.10) as independent predictors of mortality
      in AD. This may be the first study demonstrating presence of tactile
      hallucination as a strong predictor of mortality in AD. CONCLUSION: This study
      does not support the hypothesis of a higher AD mortality rate in nursing homes.

PMID- 15578676
TI  - On the way to a quality control of the essential oil of fennel by means of Raman
      spectroscopy.
AB  - Essential oils are one of the most valuable natural products. The price of
      special essential oils that can be purchased on the market strongly depends on
      the quality of the product. The quality, which depends on the quantitative and
      qualitative variation of different monoterpenes, varies with respect of the
      origin and the harvesting period. This contribution reports on a Raman
      spectroscopic study on the essential oil occurring in fennel. Cross-sections of
      fennel seed were investigated by use of Raman spectroscopy and Raman mapping to
      localize the essential oil and to analyze its chemical composition directly in
      the plant. Furthermore the practicability of a home-built mobile transportable
      Raman spectrometer to perform on-site measurements was successfully tested.

PMID- 15578677
TI  - Depression of the melting temperature by moisture for alpha-form crystallites in
      human hair keratin.
AB  - DSC thermal analysis has been carried out for human hair samples with various
      moisture contents to investigate the melting temperature depression behavior of
      alpha-form crystallites in human hair. This is achieved by adopting a novel
      technique using silicon oil as the thermal medium, which permits hair samples to
      retain a range of moisture contents in between completely dry and fully
      saturated. The results show that the melting temperature of the alpha-form
      crystallites in human hair varies with moisture content from 205 degrees C for
      dry hair to 155 degrees C for the hair sample with moisture content of 23%. These
      experimental results are particularly useful for clarification of the conceptual
      ambiguities associated with the molecular properties of alpha-helices and alpha
      form crystallites. Furthermore, the Flory-Huggins theory was employed to
      determine the water-helix interaction parameter (chi = 4.5) and the alpha-form
      crystallinity of human hair (22%), a figure consistent with that obtained by the
      XRD method (21%).

PMID- 15578678
TI  - Decomposition of neutral, singly and doubly protonated benzoquinone in the gas
      phase.
AB  - The unimolecular fragmentations of singly and doubly protonated ortho-, meta-,
      and para-benzoquinones (BQH(+) and BQH(2)(2+), respectively) are studied by
      tandem mass spectrometry. The dominant fragmentation pathways lead to the
      elimination of a neutral CO molecule from BQH(+) and, by charge separation, to
      the expulsion of protonated CO from BQH(2)(2+). Reaction mechanisms are
      elucidated based on labeling experiments and UB3 LYP calculations. These results
      reveal that the respective reactions proceed in an analogous fashion to the
      decarbonylation of neutral benzoquinones, which decompose into carbon monoxide
      and cyclopentadienone. Single protonation facilitates all steps on the reaction
      pathway with neutral CO and O-protonated cyclopentadienone as final products. In
      contrast, double protonation leads to an increase of the barriers for the
      decomposition yielding CO.H(+) and O-protonated cyclopentadienone. This major
      process of BQH(2)(2+) is accompanied by two minor channels, which lead to the
      elimination of neutral carbon monoxide and water, respectively. The proton
      affinity of the para-BQH(+) monocation is estimated as 3.6+/-0.3 eV.

PMID- 15578680
TI  - Fluorescence enhancement of fluorophores tethered to different sized silver
      colloids deposited on glass substrate.
AB  - We studied fluorescence enhancements of fluorescein tethered to silver colloids
      of different size. Thiolated 23-mer oligonucleotide (ss DNA-SH) was bound
      selectively to silver colloids deposited on 3-aminopropyltriethoxysilane (APS)
      treated quartz slides. Fluorescein-labeled complementary oligonucleotide (ss Fl
      DNA) was added in an amount significantly lower than the amount of unlabeled DNA
      tethered to the colloids. The hybridization kinetics, observed as an increase in
      fluorescence emission, on small (30-40 nm) and large (> 120 nm) colloids were
      similar. However, the final fluorescence intensity of the sample with large
      colloids was about 50% higher than that observed for the sample with small
      colloids. The reference sample without ss DNA-SH was used to estimate the
      fluorescence enhancements of fluorescein tethered to the small colloids (E = 2.7)
      and to the large colloids (E = 4.1) due to its steady fluorescence signal. The
      proposed method, based on controlled hybridization with minimal amount of
      fluorophore labeled ss DNA, can be used to reliably estimate the fluorescence
      enhancements on any silver nanostructures.

PMID- 15578681
TI  - Validation and adaptation of a nomogram for predicting the survival of patients
      with extremity soft tissue sarcoma using a three-grade system.
AB  - BACKGROUND: A nomogram for predicting long term tumor-specific death in patients
      with soft tissue sarcoma (STS) was developed at the Memorial Sloan-Kettering
      Cancer Center (MSKCC). METHODS: To assess the performance of the MSKCC nomogram,
      642 consecutive patients with extremity STS who underwent surgery over a 20-year
      span at a single referral center were analyzed. Nomogram predictions were based
      on tumor size, depth, site, patient age, histologic subtype, and grade. The
      latter, at variance with the system in use at the MSKCC, was classified as Grade
      1-3 according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC)
      system. The statistical approach used for nomogram performance assessment was
      that of "validation by calibration" proposed by Van Houwelingen. RESULTS: Graphic
      comparison of observed and predicted sarcoma-specific survival curves showed that
      predictions by the nomogram were quite accurate, within 10% of actual survival
      for all prognostic strata. Statistical analysis showed that such predictions
      could be improved by employing approximately 25% shrinkage to achieve good
      calibration. The contribution of histologic grade was highly significant in both
      univariate analysis (P < 0.001) and multivariate analysis (P < 0.001), and a
      survival trend across the 3 grade categories was observed. Based on those
      findings, a nomogram that included the FNCLCC histologic grade classification was
      produced. CONCLUSIONS: Results of the current study confirmed that the MSKCC
      nomogram is a valuable tool for individual prognostic assessment. A nomogram that
      included the FNCLCC histologic grade classification was proposed and was
      validated internally.

PMID- 15578682
TI  - Breast carcinoma in men.

PMID- 15578683
TI  - Richter syndrome: biology, incidence, and therapeutic strategies.
AB  - Richter's transformation denotes the development of high-grade non-Hodgkin
      lymphoma, prolymphocytic leukemia, Hodgkin disease, or acute leukemia in patients
      with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma. A search of
      published articles in Medline (PubMed) and abstracts from professional meetings
      was performed. An electronic database search of patients with CLL at The
      University of Texas M. D. Anderson Cancer Center (Houston, TX) determined the
      incidence of Richter syndrome (RS) in patients with CLL between 1992 and 2002. RS
      occurs in approximately 5% of patients with CLL. The large cells of RS may arise
      through transformation of the original CLL clone or represent a new neoplasm. RS
      may be triggered by viral infections, such as Epstein-Barr virus. Trisomy 12 and
      chromosome 11 abnormalities are more frequent in patients with RS than in the
      overall population of patients with CLL. Multiple genetic defects, such as
      mutations of the p53 tumor suppressor gene, p16INK4A, and p21, loss of p27
      expression, deletion of retinoblastoma, increased copy number of C-MYC, and
      decreased expression of the A-MYB gene, have been described. These abnormalities
      may cause CLL cells to proliferate and-by facilitating the acquisition of new
      genetic abnormalities-to transform into RS cells. Therapeutic strategies include
      intensive chemotherapy, monoclonal antibodies, and stem cell transplantation. The
      response rates range from 5% to 43% (complete response, 5-38%), and the median
      survival duration ranges from 5 months to 8 months. In conclusion, RS may be
      triggered by viral infections or by genetic defects. Current treatments are
      aggressive, but prognosis is poor. Novel curative treatment strategies are
      needed.

PMID- 15578684
TI  - Increased risk of brain metastases in patients with HER-2/neu-positive breast
      carcinoma.

PMID- 15578685
TI  - Up-regulation of the interferon gamma (IFN-gamma)-inducible chemokines IFN
      inducible T-cell alpha chemoattractant and monokine induced by IFN-gamma and of
      their receptor CXC receptor 3 in human renal cell carcinoma.
AB  - BACKGROUND: The antiangiogenic CXC chemokines interferon gamma (IFN-gamma)
      inducible T-cell alpha chemoattractant (I-TAC) and monokine induced by IFN-gamma
      (Mig) are known as members of IFN-gamma-inducible antiangiogenic CXC chemokines.
      However, the expression of these chemokines in highly angiogenic tumors remains
      poorly understood. The authors examined expression of I-TAC, Mig, and their
      receptor, CXCR3, in tissue samples from patients with renal cell carcinoma (RCC).
      METHODS: Twenty-one samples of untreated RCC and corresponding normal renal
      tissues were obtained from surgical specimens. The expression levels of I-TAC,
      Mig, and CXCR3 were investigated using reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis, real-time RT-PCR analysis, and Western blot analysis.
      Immunohistochemistry was carried out to clarify the localization of both
      chemokines and of CXCR3. RESULTS: RT-PCR analysis showed strong expression levels
      of I-TAC, Mig, and CXCR3 in RCC tissues and very weak or undetectable expression
      in normal kidney tissues. Real-time RT-PCR analysis showed that expression levels
      of I-TAC, Mig, and CXCR3 in RCC tissues were 14.9 times greater, 30.3 times
      greater, and 9.9 times greater compared with the levels in the corresponding
      normal kidney tissues, respectively (P < 0.01). Western blot analysis showed up
      regulation of I-TAC, Mig, and CXCR3 at the protein level. Immunofluorescence
      double stainings revealed that I-TAC coincided with pericytes and vascular smooth
      muscle cells (VSMCs) in tumor angiogenic vessels. Mig was detected in tumor
      endothelial cells (TECs) and in infiltrating leukocytes. In the corresponding
      normal kidney tissues, neither VSMCs nor endothelial cells showed positive
      stainings for these chemokines. CXCR3 was expressed in both tumor cells and
      infiltrating leukocytes. CONCLUSIONS: The results revealed special feature of
      vascular mural cells and TECs in RCC. The up-regulated I-TAC and Mig, produced by
      tumor vessels, may interact with CXCR3 expressed in tumor cells, with possible
      pathophysiologic significance in RCC progression.

PMID- 15578686
TI  - Weekly docetaxel is safe and effective in the treatment of advanced-stage
      acquired immunodeficiency syndrome-related Kaposi sarcoma.
AB  - BACKGROUND: Intravenous paclitaxel, 100 mg/m(2), given over 3 hours every 2 weeks
      is associated with a response rate of 59% in patients with recurrent or
      refractory acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS).
      However, this regimen is associated with significant myelosuppression, and the
      inconvenience of a 3-hour infusion. Moreover, no effective therapies have been
      defined for use after treatment failure with this agent. A Phase II trial was
      conducted with weekly docetaxel in patients with advanced-stage KS to assess
      safety and antitumor activity. METHODS: Docetaxel was administered at a dose of
      25 mg/m(2) intravenously over 15-30 minutes weekly for 8 weeks. Thereafter, if
      the patient experienced stable disease or better response, treatment doses were
      given every other week until complete disease remission, disease progression, or
      unacceptable toxicity occurred. RESULTS: Twelve patients were accrued-9 had > 25
      mucocutaneous lesions, 1 had lymphedema, and 2 had visceral involvement. Ten
      patients (83%) had previous systemic chemotherapy, including 4 who received
      previous paclitaxel. Treatment was well tolerated, with no Grade 4 toxicity of
      any type. Grade 3 neutropenia occurred in 33% of patients but no patient had
      neutropenic fever. Five patients (42%) achieved a partial response, including 1
      who had previously failed to respond to paclitaxel. The median time to disease
      progression was 26 months (range, 5-53 months). With a median follow-up period of
      45 months, the median survival point had not been reached. CONCLUSIONS: Weekly
      docetaxel is safe, with reasonable antitumor activity in patients with advanced
      stage, recurrent, or refractory AIDS-related KS.

PMID- 15578687
TI  - High-resolution gene copy number and expression profiling of human chromosome 22
      in ovarian carcinomas.
AB  - Previous low-resolution studies of chromosome 22 in ovarian carcinoma have
      suggested its involvement in the development of the disease. We report a high
      resolution analysis of DNA copy number and gene expression of 22q in 18 ovarian
      carcinomas using a 22q-specific genomic microarray. We identified aberrations in
      67% of the studied tumors, which displayed 3 distinct gene copy number profiles.
      The majority of the cases (11 of 18) demonstrated heterozygous terminal deletions
      of various sizes, the smallest of which was 3.5 Mb. The second profile, detected
      in 3 tumors, revealed the coexistence of heterozygous deletions and different
      patterns of low-copy-number gain that involved the proximal half of 22q. The
      latter finding has not been reported previously in ovarian carcinoma. One case
      displayed a continuous deletion encompassing the entire 22q, consistent with
      monosomy 22. Furthermore, we compared the results with the available data on
      these tumors by using cDNA microarrays to define the degree of correlation
      between abnormalities at the DNA level and variation in mRNA expression. By a
      comparison with the expression data, we were able to identify 21 deleted genes
      showing low mRNA levels and 12 amplified genes displaying elevated gene
      expression, several of which play roles in cell cycle control and the induction
      of apoptosis. Our results indicated significant correlation between DNA copy
      number aberrations and variation in mRNA expression. We also identified several
      regions and candidate genes on 22q that should be studied further to determine
      their role in the development of ovarian cancer.

PMID- 15578688
TI  - Microsatellite distribution and indication for locoregional therapy in small
      hepatocellular carcinoma.
AB  - BACKGROUND: Intrahepatic disease recurrence is observed frequently after
      locoregional therapies for patients with hepatocellular carcinoma (HCC). However,
      the indication for locoregional therapy is still unclear. To clarify the
      indication for locoregional therapy for small HCC tumors, the authors measured
      the distance of microsatellites from the main tumor and analyzed the relation
      between this distance and clinicopathologic factors. METHODS: The authors
      retrospectively analyzed 100 patients with small HCC tumors (</= 5 cm in
      dimension) treated by curative hepatectomy. A microsatellite was defined as
      invasion into the portal vein or intrahepatic metastasis, and the distance from
      the main tumor to the most distant microsatellite was determined under light
      microscopy. The current study investigated the relation between microsatellite
      distance (0 mm if none present, </= 5 mm, and > 5 mm) and clinicopathologic
      factors, as well as overall and disease-free survival rates after hepatectomy.
      RESULTS: Of the 100 patients, 46 had microsatellites with a mean distance of 9.9
      mm (median, 5.0 mm). Of the clinicopathologic factors investigated, tumor grade
      and preoperative alpha-fetoprotein level significantly correlated with the
      presence of a microsatellite. Tumor size and distance to the microsatellite were
      significantly correlated. All but 1 tumor associated with a microsatellite
      distance > 5 mm was a high-grade tumor > 25 mm in greatest dimension. The overall
      survival rate of patients with a microsatellite distance of > 5 mm was lower than
      that of patients with a microsatellite distance < 5 mm. CONCLUSIONS: Locoregional
      therapy, including limited resection and ablation therapies, was appropriate for
      patients with low-grade HCC tumors or with tumors < 25 mm in diameter.

PMID- 15578689
TI  - Family history of cancer and the risk of prostate cancer and benign prostatic
      hyperplasia.
AB  - We analysed the relation between family history of cancer in first-degree
      relatives and risk of prostate cancer (PC) and benign prostatic hyperplasia (BPH)
      using data from a multicentric case-control study conducted in Italy from 1991 to
      2002 on 1,294 cases of incident, histologically confirmed PC, 1,369 cases of BPH
      and 1,451 men admitted to the same network of hospitals for acute, nonneoplastic
      conditions. Unconditional logistic regression was used to estimate odds ratios
      (OR) of PC and BPH, adjusted for age and other confounders. Men with a family
      history of PC had an OR of PC of 4.0 (95% confidence interval [CI] 2.5-6.5), and
      the risk was higher when the proband was younger, when 2 or more relatives were
      affected or when the affected relative was a brother. The risk of PC was also
      increased in men with a family history of cancer of the ovary (OR = 6.2, 95% CI
      1.2-32), bladder (OR = 3.5, 95% CI 1.6-7.4) and kidney (OR = 3.1, 95% CI 1.1
      8.5). An involvement of breast/ovarian cancer predisposition genes in a small
      proportion of PCs was suggested by the cluster of these cancers in female
      relatives of a few PC cases. The risk of BPH was increased in men with a family
      history of bladder cancer (OR = 2.2, 95% CI 1.0-5.0) but not PC (OR = 1.2, 95% CI
      0.7-2.2). Our study adds further information on the association of family history
      of cancer and risk of PC and is, to our knowledge, the first comprehensive
      epidemiologic information on family history of cancer and risk of BPH.

PMID- 15578690
TI  - Efficacy of a rapamycin analog (CCI-779) and IFN-gamma in tuberous sclerosis
      mouse models.
AB  - Tuberous sclerosis complex (TSC) is a familial tumor disorder for which there is
      no effective medical therapy. Disease-causing mutations in the TSC1 or TSC2 gene
      lead to increased mammalian target of rapamycin (mTOR) kinase activity in the
      conserved mTOR signaling pathway, which regulates nutrient uptake, cell growth,
      and protein translation. The normal function of TSC1 and TSC2 gene products is to
      form a complex that reduces mTOR kinase activity. Thus, mTOR kinase inhibition
      may be a useful targeted therapeutic approach. Elevated interferon-gamma (IFN
      gamma) expression is associated with decreased severity of kidney tumors in TSC
      patients and mouse models; therefore, IFN-gamma also has therapeutic potential.
      We studied cohorts of Tsc2+/- mice and a novel mouse model of Tsc2-null tumors in
      order to evaluate the efficacy of targeted therapy for TSC. We found that
      treatment with either an mTOR kinase inhibitor (CCI-779, a rapamycin analog) or
      with IFN-gamma reduced the severity of TSC-related disease without significant
      toxicity. These results constitute definitive preclinical data that justify
      proceeding with clinical trials using these agents in selected patients with TSC
      and related disorders.

PMID- 15578691
TI  - Synthesis and structures of cycloalkylidene-bridged cyclopentadienyl metallocene
      catalysts: effects of the bridges of ansa-metallocene complexes on the catalytic
      activity for ethylene polymerization.
AB  - A series of cycloalkylidene-bridged cyclopentadienyl metallocene complexes,
      [(CH(2))(n)C(C(5)H(4))(2)MCl(2)] (M = Ti, n = 4 (4), 5 (5), 6 (6); M = Zr, n = 4
      (7), 5 (8), 6 (9); M = Hf, n = 4 (10), 5 (11), 6 (12)), have been synthesized and
      applied to ethylene polymerization after activation with methyl aluminoxane
      (MAO). The cycloalkylidene-bridged titanocene catalysts exhibit much higher
      activities than the corresponding zirconocene and hafnocene analogues, and have
      the highest activities at higher temperatures. In comparison, the
      silacyclopentylidene-bridged metallocene complexes
      [(CH(2))(4)Si(C(5)H(4))(2)MCl(2)] (M = Ti (13), Zr (14)) and isopropylene-bridged
      metallocene complexes [Me(2)C(C(5)H(4))(2)MCl(2)] (M = Ti (15), Zr (16)) have
      also been synthesized and applied to ethylene polymerization. In both cases, the
      titanocene complexes show much higher activities than the corresponding
      zirconocene analogues, especially at a lower temperature. The molecular
      structures of complexes 4-9 have been determined by X-ray diffraction. The
      structure-activity relationships, especially the effects of the bridges of ansa
      metallocene complexes, are discussed.

PMID- 15578692
TI  - Competition between superexchange-mediated and sequential electron transfer in a
      bridged donor-acceptor system.
AB  - The temperature- and solvent-dependence of photoinduced electron-transfer
      reactions in a porphyrin-based donor-bridge-acceptor (DBA) system is studied by
      fluorescence and transient absorption spectroscopy. Two competing processes
      occur: sequential and direct superexchange-mediated electron transfer. In a
      weakly polar solvent (2-methyltetrahydrofuran), only direct electron transfer
      from the excited donor to the appended acceptor is observed, and this process has
      weak temperature dependence. In polar solvents (butyronitrile and
      dimethylformamide), both processes are observed and the sequential electron
      transfer shows strong temperature dependence. In systems where both electron
      transfer processes are observed, the long-range superexchange-mediated process is
      more than two times faster than the sequential process, even though the donor
      acceptor distance is significantly larger in the former case.

PMID- 15578693
TI  - NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer
      cases in Russia.
AB  - The gene for Nijmegen chromosomal breakage syndrome (NBS1) plays a role in a
      variety of processes protecting chromosomal stability. Recently, it was suggested
      in a Polish case-control study that the founder hypomorphic mutation in NBS1,
      657del5, which occurs in approximately 0.5% of Slavic subjects, may be associated
      with an increased risk of breast cancer (BC). We attempted to validate these
      findings in Russian subjects, who are also of Slavic descent. Heterozygous
      carriers for the 657del5 mutation were detected in 2 of 173 (1.16%) bilateral
      breast cancer cases, 5 of 700 (0.71%) unilateral breast cancer patients, 2 of 348
      (0.57%) healthy middle-aged females and in 0 of 344 elderly tumor-free women. The
      difference between the "extreme" cohorts, i.e., biBC patients vs. elderly
      controls, approached the formal limit of statistic significance (p=0.046). LOH at
      NBS1 was detected in only 3 of 5 available breast tumors from NBS1 657del5
      carriers. In 2 of these tumors, the loss involved the mutant NBS1-allele.
      Overall, our data suggest that the NBS1 657del5 allele may contribute only to a
      limited fraction of breast cancer cases in Russia.

PMID- 15578694
TI  - Cancer risk among statin users: a population-based cohort study.
AB  - Hydroxymethylglutaryl-CoA reductase inhibitors (statins) have been linked with
      potential chemopreventive effects; however, the data are conflicting. We
      conducted a population-based cohort study using data from the Prescription
      Database of North Jutland County and the Danish Cancer Registry for the period
      1989-2002. In a study population of 334,754 county residents, we compared overall
      and site-specific cancer incidence among 12,251 statin users (> or =2
      prescriptions) with cancer incidence among nonusers and users of other lipid
      lowering drugs (n = 1,257). Statistical analyses were based on age
      standardization and Poisson regression analysis, adjusting for age, gender,
      calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular
      drugs. We identified 398 cancer cases among statin users during a mean follow-up
      period of 3.3 years (range 0-14 years). The age- and gender-standardized
      incidence rates of cancer overall were 596 per 100,000 person-years among statin
      users, 645 per 100,000 person-years among nonusers and 795 per 100,000 person
      years among users of other lipid-lowering drugs. Adjusted rate ratios for cancer
      overall among statin users were 0.86 (95% CI, 0.78-0.95) compared to nonusers and
      0.73 (95% CI, 0.55-0.98) compared to users of other lipid-lowering drugs. No
      significantly increased or decreased rate ratios were observed for any of the
      studied site-specific cancers (liver, colorectum, lung, breast, prostate, female
      genital organs and lymphatic and haematopoietic tissue), but most estimates
      tended to be less than 1.0. Stratification by duration of follow-up or number of
      prescriptions revealed no clear trends. In summary, individuals prescribed
      statins experienced a slightly reduced cancer incidence compared to population
      controls of nonusers and users of other lipid-lowering drugs. Larger and longer
      term studies are needed to determine the potentially protective effect of statin
      use on cancer development.

PMID- 15578695
TI  - Polyoxometalate-supported Y- and YbIII-hydroxo/oxo clusters from carbonate
      assisted hydrolysis.
AB  - Carbonate-assisted hydrolysis of Y or Yb(III) ions in the presence of the
      trivacant Wells-Dawson polyoxoanion, alpha-[P(2)W(15)O(56)](12-), produced two
      polyoxometalate-supported Y- or Yb(III)-hydroxo/oxo clusters, which have been
      characterized by single-crystal X-ray structure determination. The structure of
      the Y complex consists of a distorted Y(4)(OH)(4) cubane cluster encapsulated by
      two lacunary alpha-[P(2)W(15)O(56)](12-) units, while the Yb cluster features a
      hexametallic core centered around a mu(6)-oxo atom with each Yb(3)(III)
      triangular face capped by an oxo or a hydroxo group. Magnetization measurements
      of the ytterbium(III) derivative suggested that intermolecular dipolar exchange
      is present at low temperatures (below 15 K). Despite its absence in the
      structures themselves, control experiments show that carbonate not only functions
      in the hydrolysis, it also influences the structure of the complexes by
      complexation to yttrium and the f-block elements.

PMID- 15578696
TI  - p53-R175H mutant gains new function in regulation of doxorubicin-induced
      apoptosis.
AB  - Mutation of tumor suppressor p53 gene gains new function in regulation of DNA
      damage-induced apoptotic response in tumor cells, which may lead to a poor
      response in cancer chemotherapy and radiotherapy. Transfection of mutant p53
      (R175H) to p53-null osteosarcoma Saos-2 cells suppressed apoptosis induced by
      doxorubicin (DOX), cisplatin and gamma radiation. Downregulation of caspase-3 but
      not -8 or -9 basal protein levels was also observed in Saos-2 cells transfected
      with p53-R175H. After 48 hr of DOX treatment, the rate of procasapse-3 activation
      into 17 kDa active form was about 3-fold higher in the control cells than that in
      the p53-R175H counterpart. Gene silencing of p53-R175H expression by p53 siRNA
      upregulate the procaspase-3 protein level and restored DOX-induced apoptosis in
      p53-R175H cells. Our results suggest that p53-R175H mutation may gain new
      function in decreasing DOX-induced apoptotic response through suppression of
      caspase-3 level and its activation.

PMID- 15578697
TI  - The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression
      of the chemokine IP-10: importance of mRNA half-life regulation.
AB  - The latent membrane protein 1 (LMP1) of Epstein-Barr Virus (EBV) is the main
      inducer of immuno-modulatory molecules affecting growth and survival of EBV
      infected cells. However, the network of signalling pathways involved remains to
      be elucidated. Here we show that LMP1 may regulate cellular genes like IFN-gamma
      inducible protein-10 kDa (IP-10) not only through transcriptional but also post
      transcriptional mechanisms. LMP1-mediated IP-10 expression is independent from
      IFN-gamma, TNF-alpha or IL-18. Transcriptional activation of IP-10 by LMP1 or
      CD40 stimulation depends on an NF-kappaB motif within the proximal 435 bp
      fragment. Carboxy-terminal activating regions 1 or 2 of LMP1 are sufficient to
      direct IP-10 promoter activation. IP-10 induction is inhibited by blockade of
      p38/SAPK2 with SB 202190, which results in decreased IP-10 mRNA half-life without
      affecting IP-10 promoter activity. Thus, LMP1-mediated p38/SAPK2 activation
      regulates transcript stability. This new mechanism of gene regulation
      demonstrates the potential of the oncoprotein LMP1 to orchestrate a network of
      signalling pathways at different regulatory levels including mRNA stability.

PMID- 15578698
TI  - Morpholino antisense oligomer targeting human midkine: its application for cancer
      therapy.
AB  - Overexpression of a heparin-binding growth factor, midkine (MK), has been
      observed in many malignancies, making it an attractive therapeutic target. We
      used morpholino antisense oligomers to downregulate human MK expression in human
      prostate (PC-3) and colon carcinoma (SW620) cells, and determined the practical
      advantages of this anticancer therapeutic. Morpholino antisense oligomers
      directed against MK caused a dramatic and sequence-specific decrease of the
      target protein level, resulting in the inhibition of growth and anchorage
      independent growth of the transfected cells. Furthermore, MK morpholino antisense
      oligomers exhibited a significant anticancer effect in the PC-3- and SW620
      xenograft models. In comparison with phosphorothioate-modified
      oligodeoxynucleotide, morpholino oligomers showed 2 major advantages, stability
      and non-toxicity. MALDI-TOF mass spectrometric analysis showed that morpholino
      antisense oligomers were completely stable in the presence of serum nuclease(s).
      Serological examinations demonstrated no toxicity of MK morpholino antisense
      oligomers. Our study indicates that inhibition of MK expression by morpholino
      antisense oligomer is a promising novel and safe therapeutic strategy for
      cancers.

PMID- 15578699
TI  - Colorectal cancer risk in individuals with biallelic or monoallelic mutations of
      MYH.

PMID- 15578700
TI  - Multiplicity of abnormal promoter methylation in lung adenocarcinomas from
      smokers and never smokers.
AB  - The prevalence of methylation of the p16, DAPK and RASSF1A genes was investigated
      in lung adenocarcinoma from smokers, former uranium miners and never smokers. The
      association between a common genetic alteration in adenocarcinoma, mutation of
      the K-ras gene and methylation of these genes, as well as survival was examined.
      Adenocarcinomas from 157 smokers, 46 never smokers and 34 former uranium miners
      were evaluated for methylation of the p16, DAPK and RASSF1A genes using the
      methylation-specific PCR assay. Comparisons were also made to prevalences of
      methylation of the MGMT gene and mutation of the K-ras gene previously examined
      in these tumors. The prevalence of methylation for all genes was similar between
      adenocarcinomas from smokers and never smokers, although the prevalence for
      methylation of the p16 gene tended to be higher in smokers compared to never
      smokers. A significantly higher prevalence for p16 methylation was seen in
      central vs. peripheral lung tumors. At least 1 gene was methylated in 35% of
      stage I tumors, whereas 2 and >/=3 genes were methylated in 40% and 16% of
      tumors, respectively. Methylation of all genes was independent of K-ras mutation,
      whereas methylation of the DAPK and RASSF1A genes was positively associated.
      Environmental tobacco smoke, the strongest lung cancer risk factor among never
      smokers, induces adenocarcinoma in part through inactivation of the p16, DAPK and
      RASSF1A genes. Adenocarcinomas may develop through 2 distinct processes: multiple
      gene inactivations through promoter hypermethylation and activation of the K-ras
      gene.

PMID- 15578701
TI  - Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid.
AB  - Valproic acid (VA) is a well-tolerated drug used to treat seizure disorders and
      has recently been shown to inhibit histone deacetylase (HDAC). Because HDAC
      modulates chromatin structure and gene expression, parameters considered to
      influence radioresponse, we investigated the effects of VA on the
      radiosensitivity of human brain tumor cells grown in vitro and in vivo. The human
      brain tumor cell lines SF539 and U251 were used in our study. Histone
      hyperacetylation served as an indicator of HDAC inhibition. The effects of VA on
      tumor cell radiosensitivity in vitro were assessed using a clonogenic survival
      assay and gammaH2AX expression was determined as a measure of radiation-induced
      DNA double strand breaks. The effect of VA on the in vivo radioresponse of brain
      tumor cells was evaluated according to tumor growth delay analysis carried out on
      U251 xenografts. Irradiation at the time of maximum VA-induced histone
      hyperacetylation resulted in significant increases in the radiosensitivity of
      both SF539 and U251 cells. The radiosensitization was accompanied by a prolonged
      expression of gammaH2AX. VA administration to mice resulted in a clearly
      detectable level of histone hyperacetylation in U251 xenografts. Irradiation of
      U251 tumors in mice treated with VA resulted in an increase in radiation-induced
      tumor growth delay. Valproic acid enhanced the radiosensitivity of both SF539 and
      U251 cell lines in vitro and U251 xenografts in vivo, which correlated with the
      induction of histone hyperacetylation. Moreover, the VA-mediated increase in
      radiation-induced cell killing seemed to involve the inhibition of DNA DSB
      repair.

PMID- 15578702
TI  - Analysis of allelic imbalances at multiple cancer-related chromosomal loci and
      microsatellite instability within the same tumor using a single tumor gland from
      colorectal carcinomas.
AB  - Genetic changes related to colorectal carcinomas are accumulated in individual
      tumor glands during disease progression. Microsatellite allelic analysis of
      individual tumor glands from 30 colorectal carcinomas using a polymerase chain
      reaction (PCR) assay coupled with crypt isolation was used to detect intratumoral
      genetic heterogeneity, the sequence of allelic imbalances (AIs) and the
      microsatellite instability status of single tumor glands during neoplastic
      progression. In addition, the CpG islands methylated phenotype (CIMP) status was
      examined using a methylation-specific PCR method. The specimens were divided into
      2 groups: a pooled gland sample, which was composed of more than 50 tumor glands,
      and a single tumor gland sample. The latter consisted of 10 single tumor glands,
      which were obtained from the same tumor separately. Most colorectal carcinomas
      (27 of 30 tumors) examined were heterogeneous for at least one genetic
      alteration, with from 2 to 7 genotypically different subclones detected per
      tumor. In 12 of the 27 heterogeneous tumors, it was possible to define the order
      of genetic alterations during the tumor progression. By analyzing multiple single
      tumor glands within the same tumor, we found that various subclonal expansions
      were seen within the same tumors. Finally, the AI pattern of single tumor glands
      was not correlated with CIMP status. Most carcinomas appeared to have a
      heterogeneous composition. This may have resulted from the successful progression
      of one clone that had different AIs in many chromosomal regions. This suggests
      that knowledge of the different genotypes of multiple single tumor glands may
      help clarify the process of tumor progression.

PMID- 15578703
TI  - Suppression of human melanoma tumor growth in SCID mice by a human high molecular
      weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody.
AB  - The lack of efficacy of available therapies for the treatment of malignant
      melanoma has emphasized the need to develop novel therapeutic strategies to
      prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is
      able to inhibit human melanoma tumor growth in SCID mice because in vitro data
      suggested that this antigen plays a role in spreading, migration and invasion of
      melanoma cells. Tumors were established by subcutaneous injection of the human
      melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the
      mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100
      microg/injection. Within 14 days after the first administration of the mAb
      225.28S, tumor growth was reduced by 52% as compared to control mice. Three
      hundred and seven genes of >20,000 genes contained on the GeneChip were changed
      in their expression level at least 2-fold after administration of the mAb
      225.28S. The encoded proteins were mostly components or modifiers of the
      extracellular matrix, tumor suppressors, and melanogenesis associated proteins.
      Surprisingly, the administration of the control mAb that did not lead to a
      significant tumor growth inhibition in vivo resulted in the modulation of two
      thirds of these genes. This is the first report of suppression of human melanoma
      tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW
      MAA mAbs may represent useful reagents to apply passive immunotherapy to patients
      with malignant melanoma.

PMID- 15578704
TI  - Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung
      cancer in a Chinese population.
AB  - p73, a structural and functional homologue of p53, shares some p53-like tumor
      suppressor activity but also possesses oncogenic activity. Therefore, p73 plays
      an important role in modulating cell-cycle control and apoptosis. A potentially
      functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the
      5' untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically
      form a stem-loop structure and affect gene expression. To test the hypothesis
      that these 2 common variants play a role in lung cancer susceptibility, we
      conducted a case-control study of 425 lung cancer patients and 588 cancer-free
      controls frequency-matched to the cases on age and sex in a Chinese population.
      The results showed that these 2 polymorphisms were in complete linkage
      disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less
      common in the cases (0.225) than in the controls (0.287) (p = 0.0018), suggesting
      that this AT haplotype was protective against lung cancer. Compared to the p73
      GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes
      were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI:
      0.26-0.80 and OR: 0.70, 95% CI: 0.53-0.92, respectively). These results suggest
      that this p73 dinucleotide polymorphism may have a role in lung cancer
      susceptibility in our study population. Further studies are needed to elucidate
      potential functional relevance of the p73 AT variant allele.

PMID- 15578705
TI  - Pristane in diesel exhaust a possible link to multiple myeloma.

PMID- 15578706
TI  - Synthesis and photochemistry of beta,beta'-di(2-furyl)-substituted o
      divinylbenzenes: intra- and/or intermolecular cycloaddition as an effect of
      annelation.
AB  - New heteroaryl-substituted o-divinylbenzenes, 2,2'-(1,2
      phenylenedivinylene)difuran (9), 2,2'-(1,2-phenylenedivinylene)bisbenzo[b]furan
      (10), and 2,2'-(1,2-phenylenedivinylene)bisnaphtho[2,1-b]furan (11), were
      prepared and irradiated at various concentrations; intramolecular
      photocycloaddition and intermolecular [2+2] twofold photoaddition reactions took
      place to give bicyclo[3.2.1]octadiene derivatives 12-14 and cyclophane
      derivatives 15-17, respectively. Compound 11 was the most selective of these o
      divinylbenzenes, which, owing to pi-pi intra- or intermolecular complexation,
      gave only the exo-bicyclo[3.2.1]octadiene derivative 14 at low concentrations,
      and only the cyclophane derivative 17 at high concentrations.

PMID- 15578707
TI  - Vitamin C uptake and recycling among normal and tumor cells from the central
      nervous system.
AB  - Specialized cells transport vitamin C in its reduced form using sodium-dependent
      cotransporters (SVCT1 and SVCT2). Additionally, different cells transport the
      oxidized form of vitamin C, dehydroascorbic acid, through glucose transporters
      (GLUTs). We have proposed recently a model for vitamin C uptake that resolves the
      apparent contradiction that although only ascorbic acid is detectable in vivo,
      there are cells that transport only dehydroascorbic acid. We carried out a
      detailed kinetic analysis to compare the mechanisms of vitamin C uptake in normal
      human melanocytes, neurons isolated from brain cortex, hypothalamic ependymal
      glial cells, and astrocytes. Uptake of ascorbic acid was also analyzed in the
      human oligodendroglioma cell line TC620, in human choroid plexus papilloma cells
      (HCPPC-1), and in the neuroblastoma cell line Neuro-2a. Melanocytes were used to
      carry out a detailed analysis of vitamin C uptake. Analysis of the transport data
      by the Lineweaver-Burk plot revealed the presence of one functional component
      (K(m) 20 microM) involved in ascorbic acid transport by melanocytes. Vitamin C
      sodium-dependent saturable uptake was also observed in neurons and hypothalamic
      tanycytes. We confirmed SVCT2 expression in neurons by in situ hybridization;
      however, SVCT2 expression was not detected in astrocytes in situ. Functional data
      indicate that astrocytes transport mainly dehydroascorbic acid, using the glucose
      transporter GLUT1. Our functional uptake analyses support the hypothesis that
      astrocytes are involved in vitamin C recycling in the nervous system. This
      recycling model may work as an efficient system for the salvage of vitamin C by
      avoiding the hydrolysis of dehydroascorbic acid produced by antioxidative
      protection.

PMID- 15578708
TI  - Evidence for shutter-speed variation in CR bolus-tracking studies of human
      pathology.
AB  - The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR)
      bolus-tracking (B-T) data assumes that the mean intracellular water molecule
      lifetime (tau(i)) is effectively zero. This assertion is inconsistent with a
      considerable body of physiological measurements. Furthermore, theory and
      simulation show the B-T time-course shape to be very sensitive to the tau(i)
      magnitude in the physiological range (hundreds of milliseconds to several
      seconds). Consequently, this standard model aspect can cause significant
      underestimations (factors of 2 or 3) of the two parameters usually determined:
      K(trans), the vascular wall CR transfer rate constant, and v(e), the CR
      distribution volume (the extracellular, extravascular space fraction). Analyses
      of animal model data confirmed two predicted behaviors indicative of this
      standard model inadequacy: (1) a specific temporal pattern for the mismatch
      between the best-fitted curve and data; and (2) an inverse dependence of the
      curve's K(trans) and v(e) magnitudes on the CR dose. These parameters should be
      CR dose-independent. The most parsimonious analysis allowing for realistic tau(i)
      values is the 'shutter-speed' model. Its application to the experimental animal
      data essentially eliminated the two standard model signature inadequacies. This
      paper reports the first survey for the extent of this 'shutter-speed effect' in
      human data. Retrospective analyses are made of clinical data chosen from a range
      of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma
      breast tumor, and osteosarcoma in the leg) that provides a wide variation,
      particularly of K(trans). The signature temporal mismatch of the standard model
      is observed in all cases, and is essentially eliminated by use of the shutter
      speed model. Pixel-by-pixel maps show that parameter values from the shutter
      speed analysis are increased by more than a factor of 3 for some lesion regions.
      This endows the lesions with very high contrast, and reveals heterogeneities that
      are often not seen in the standard model maps. Normal muscle regions in the leg
      allow validation of the shutter-speed model K(trans), v(e), and tau(i)
      magnitudes, by comparison with results of previous careful rat leg studies not
      possible for human subjects.

PMID- 15578709
TI  - Theoretical investigations of prostatic acid phosphatase.
AB  - The phosphotyrosyl protein phosphatase activity of prostatic acid phosphatase
      (PAP) has been well established. It has also been suggested that PAP partly
      regulates the activity of growth factor receptors by dephosphorylating the
      autophosphorylysable tyrosines in them. We studied the binding of the peptides
      from epidermal growth factor receptor (EGFR) and its homolog (ErbB-2),
      corresponding to their autophosphorylation sites, to PAP using theoretical
      modeling and molecular dynamics (MD) simulation methods. Nine different peptides,
      each with a phosphotyrosine residue, were docked on human PAP. The binding
      energies of these peptide-PAP complexes were calculated theoretically and
      compared to experimentally obtained affinities. The peptide Ace--DNLpYYWD--NH2
      from ErbB-2(1197-1203) showed the most favorable free energy of binding when
      estimated theoretically. The results demonstrate that the presence of another
      tyrosine residue proximate to C-terminal of autophosphorylysable Tyr enhances the
      binding affinity considerably. The presence of a bulky group instead prevents the
      binding, as is observed in case of peptide Ace--NLYpYWDQ--NH2 which failed to
      bind, both in theoretical calculations and experiments. Thus we demonstarted that
      PAP could potentially bind to EGFR and Erbb-2 and dephosphorylate them. Thus it
      could be involved in the regulation of the function of such receptors. In
      addition, complexes of a peptide from AngiotensinII and phosphotyrosine(pY) with
      human PAP were also modeled. The effects of different protonation states of the
      titratable active site residues on ligand (pY) binding have also been
      investigated. For a favorable binding His12 and Asp258 should be neutral, His257
      should be positively charged and the phosphate group of the ligand should be in
      PO(4) (3-) state. Furthermore, the analysis of protein motion as observed during
      simulations suggests the loop-loop contact in the PAP dimer to be of importance
      in cooperativity.

PMID- 15578710
TI  - A DFT-based theoretical investigation of the mechanism of the PtCl2-mediated
      cycloisomerization of allenynes.
AB  - The mechanism of Pt(II)-catalyzed intramolecular cycloisomerization of allenyne
      systems has been extensively investigated by DFT calculations. Different
      mechanistic schemes have been proposed and discussed, including the Alder-ene
      reaction. The free energy results suggest that the kinetically preferred reaction
      pathway for precursors that are tri- and tetrasubstituted on the allene moiety
      should proceed by a five-step mechanism. This would involve formation of a
      platina(IV)cyclopentene intermediate by selective engagement of the external pi
      bond of the allene, which would undergo regioselective beta-H elimination from
      the equatorially disposed methyl group. A metal-induced H migration leads to a
      second octahedral Pt(IV)-chelate complex, which would yield the expected bicyclic
      system through an intramolecular migratory insertion step. Therefore, depending
      on the conformation of the initial eta(4)-reactant complex for trisubstituted
      patterns, two possible intermediates can be formed that would evolve through
      different paths. In these cases, the regio- and stereochemical outcomes predicted
      by the mechanistic scheme proposed agree with experimental data. Substituted
      precursors on the alkyne moiety follow a distinct, four-step, mechanism also
      involving an oxidative cyclometalation process to an octahedral Pt(IV)
      intermediate complex. Theoretical results reveal the kinetic preference for beta
      H elimination from the allylic group rather than from the gem-dimethyl group,
      which should account for the observed regioselectivity.

PMID- 15578711
TI  - Up-regulated expression of cytoplasmic clusterin in human ovarian carcinoma.
AB  - BACKGROUND: Recently, tumorigenic roles of the clusterin gene in several human
      malignancies have been suggested, but its potential role in the development and
      progression of ovarian carcinoma is unclear. METHODS: In the current study,
      immunohistochemistry was used to examine the expression status of clusterin in 10
      normal ovaries, 20 ovarian cystadenomas, 15 borderline ovarian tumors, and 240
      ovarian carcinomas (nonmetastatic and metastatic) by tissue microarray. In
      addition, the apoptotic index of each tumor was assessed with a terminal
      deoxyuridine triphosphate nick-end labeling assay. RESULTS: Positive staining for
      clusterin in different ovarian tissues was observed primarily a cytoplasmic
      pattern. Cytoplasmic overexpression of clusterin was detected in none of the
      normal ovaries, in 17% of cystadenomas, in 38% of borderline tumors, and in 58%
      of invasive ovarian carcinomas. A significant association was observed (P <
      0.001) between the overexpression of clusterin and late clinical stage according
      to the International Federation of Gynecology and Obstetrics staging system. In
      addition, the overexpression of clusterin was detected more frequently in
      metastatic lesions than that in their matched primary tumors. The current results
      also provided evidence that the overexpression of cytoplasmic clusterin in
      carcinomas was correlated inversely with the tumors' apoptotic index,
      demonstrating an antiapoptotic function of cytoplasmic clusterin in ovarian
      carcinomas. CONCLUSIONS: The current results suggested that the overexpression of
      cytoplasmic clusterin may represent an acquired malignant phenotypic feature of
      ovarian carcinoma and may be one of the important factors in determining the
      aggressive nature of ovarian carcinoma.

PMID- 15578712
TI  - Use of positron emission tomography in localized extremity soft tissue sarcoma
      treated with neoadjuvant chemotherapy.
AB  - BACKGROUND: Patients with high-grade soft tissue sarcomas are at high risk of
      developing local disease recurrence and metastatic disease. [F-18]-fluorodeoxy-D
      glucose (FDG) positron emission tomography (PET) scans are hypothesized to detect
      histopathologic response to therapy and to predict risk of tumor progression in
      patients with various malignancies. Serial FDG-PET scans were taken to determine
      the correlation between FDG uptake and patient outcomes in patients receiving
      multimodality treatment of extremity sarcomas. METHODS: Forty-six patients with
      high-grade localized sarcomas were studied. The maximum standardized uptake
      values (SUVmax) of tumors were measured before receipt of neoadjuvant
      chemotherapy and again before surgery. Resected specimens were examined for
      residual viable tumor. Patients were followed up at least annually for evidence
      of local and distant recurrence of disease and survival. RESULTS: Patients with a
      baseline tumor SUVmax >/= 6 and < 40% decrease in FDG uptake were at high risk of
      systemic disease recurrence estimated to be 90% at 4 years from the time of
      initial diagnosis. Patients whose tumors had a >/= 40% decline in the SUVmax in
      response to chemotherapy were at a significantly lower risk of recurrent disease
      and death after complete resection and adjuvant radiotherapy. CONCLUSIONS: The
      FDG-PET scan was found to be a useful method with which to predict the outcomes
      of patients with high-grade extremity soft tissue sarcomas treated with
      chemotherapy. The pretreatment tumor SUVmax and change in SUVmax after
      neoadjuvant chemotherapy independently identified patients at high risk of tumor
      recurrence. The FDG-PET scan showed promise as a tool to identify the patients
      with sarcoma who are most likely to benefit from chemotherapy.

PMID- 15578713
TI  - Developmental gene expression profiling of mammalian, fetal orofacial tissue.
AB  - BACKGROUND: The embryonic orofacial region is an excellent developmental paradigm
      that has revealed the centrality of numerous genes encoding proteins with diverse
      and important biological functions in embryonic growth and morphogenesis. DNA
      microarray technology presents an efficient means of acquiring novel and valuable
      information regarding the expression, regulation, and function of a panoply of
      genes involved in mammalian orofacial development. METHODS: To identify
      differentially expressed genes during mammalian orofacial ontogenesis, the
      transcript profiles of GD-12, GD-13, and GD-14 murine orofacial tissue were
      compared utilizing GeneChip arrays from Affymetrix. Changes in gene expression
      were verified by TaqMan quantitative real-time PCR. Cluster analysis of the
      microarray data was done with the GeneCluster 2.0 Data Mining Tool and the
      GeneSpring software. RESULTS: Expression of >50% of the approximately 12,000
      genes and expressed sequence tags examined in this study was detected in GD-12,
      GD-13, and GD-14 murine orofacial tissues and the expression of several hundred
      genes was up- and downregulated in the developing orofacial tissue from GD-12 to
      GD-13, as well as from GD-13 to GD-14. Such differential gene expression
      represents changes in the expression of genes encoding growth factors and
      signaling molecules; transcription factors; and proteins involved in epithelial
      mesenchymal interactions, extracellular matrix synthesis, cell adhesion,
      proliferation, differentiation, and apoptosis. Following cluster analysis of the
      microarray data, eight distinct patterns of gene expression during murine
      orofacial ontogenesis were selected for graphic presentation of gene expression
      patterns. CONCLUSIONS: This gene expression profiling study identifies a number
      of potentially unique developmental participants and serves as a valuable aid in
      deciphering the complex molecular mechanisms crucial for mammalian orofacial
      development.

PMID- 15578714
TI  - Genetic approaches to identify disease genes for birth defects with cleft
      lip/palate as a model.
AB  - BACKGROUND: Understanding the etiology of birth defects is an important step
      toward developing improved treatment and preventive strategies. Most birth
      defects have an underlying genetic basis, ranging from single genes playing
      dominant or recessive roles in Mendelian disorders to a mixture of contributions
      from multiple genes and environmental triggers in complex traits. The purpose of
      this article is to provide an overview of genetic approaches to identifying
      disease genes for genetically complex birth defects. METHODS: A review of the
      literature describing successes and limitations for identifying disease genes for
      complex traits was conducted. RESULTS: Cleft lip and cleft palate are common
      congenital anomalies with significant medical, psychological, social, and
      economic ramifications. The Online Mendelian Inheritance in Man catalog (OMIM;
      http://www3.ncbi.nlm.nih.gov/Omim) lists more than 400 single-gene causes of
      clefts of the lip and/or palate. Genetic causes of clefting also include
      chromosomal rearrangements, genetic susceptibility to teratogenic exposures, and
      complex genetic contributions of multiple genes. CONCLUSIONS: Genetic causes of
      birth defects can be identified using an increasingly powerful combination of
      careful sample collection, molecular analytic methods, and statistical
      evaluations. We will describe a range of approaches to search for genetic factors
      of birth defects and use our own work with cleft lip and palate as a model.

PMID- 15578715
TI  - Prostate carcinoma detection and increased prostate-specific antigen levels after
      4 years in Dutch and Japanese males who had no evidence of disease at initial
      screening.
AB  - BACKGROUND: In the current study, the authors set out to investigate the
      possibility that increased prostate-specific antigen (PSA) levels in Dutch and
      Japanese men without suspicious findings at initial prostate cancer screening
      were indicative of the risk of newly developing clinical malignancy in the
      Netherlands and Japan. METHODS: Between 1992 and 2000, 2650 men ages 55-74 years
      who had PSA levels < 4.0 ng/mL and no suspicious findings on digital rectal
      examination were entered into the current study from a population-based prostate
      cancer screening cohort in Gunma Prefecture, Japan. In addition, between 1994 and
      1997, 3163 men with the same clinical background were entered into the current
      study from the Rotterdam (Netherlands) Section of the European Randomized Study
      of Screening for Prostate Cancer (ERSPC). Prostate carcinoma incidence and the
      cumulative probability of freedom from PSA increases to levels > 2.0, 3.0, and
      4.0 ng/mL, respectively, after 4 years of observation were compared between the
      Japanese and Dutch populations. The predictive value of initial PSA level, age at
      study entry, and geographic location also were investigated using Cox
      proportional hazards models. RESULTS: The overall risk of developing prostate
      carcinoma during the 4-year observation period was significantly higher for the
      ERSPC Rotterdam cohort (5.2%) compared with the Gunma cohort (1.6%). The
      cumulative probability of freedom from prostate carcinoma detection and freedom
      from an increase in PSA levels to >/= 4.0 ng/mL (PSA progression) decreased
      significantly with increasing initial PSA level and did not differ significantly
      between Japanese and Dutch patients whose initial PSA levels fell within the same
      range (0.0-0.9, 1.0-1.9, 2.0-2.9, or 3.0-3.9 ng/mL). Multivariate analysis also
      revealed that after controlling for age and initial PSA level, the probability of
      PSA progression was the same for Japanese and Dutch men. Initial PSA level was
      the only variable found to be significantly predictive of PSA progression on
      multivariate analysis (P < 0.0001). CONCLUSIONS: The risk of developing prostate
      carcinoma within a given 4-year period is greater for Dutch males ages 55-69
      years compared with their Japanese counterparts, because the former have higher
      PSA levels. Nonetheless, there appears to be no significant difference in
      prostate carcinoma risk between Dutch and Japanese males whose baseline PSA
      levels fall within the same range.

PMID- 15578716
TI  - Mcl-1 expression in gestational trophoblastic disease correlates with clinical
      outcome: a differential expression study.
AB  - BACKGROUND: Hydatidiform moles (HMs) are abnormal pregnancies with a propensity
      for developing persistent disease in the form of gestational trophoblastic
      neoplasia (GTN), which requires chemotherapy. In previous studies, the authors
      demonstrated that low apoptotic activity was correlated with the progression of
      HM to GTN, and they hypothesized that some apoptosis-related genes may determine
      this progression. METHODS: The differential expression of apoptotic genes in HMs
      that subsequently developed into GTN was compared with the same expression in HMs
      that spontaneously regressed using a human apoptosis array; then, the expression
      was evaluated with real-time quantitative polymerase chain reaction analysis and
      immunohistochemistry using 54 clinical samples from patients with HMs who had
      follow-up data available. RESULTS: Using an apoptosis array, greater expression
      of Mcl-1, which is an antiapoptotic gene, was detected in HMs that subsequently
      developed into GTN. It was confirmed that the levels of Mcl-1 RNA expression (P =
      0.017) and Mcl-1 protein expression (P < 0.001) in HMs that developed into
      persistent disease and required chemotherapy were significantly greater compared
      with the levels in HMs that regressed. Moreover, Mcl-1 immunoreactivity, which
      was detected predominantly in cytotrophoblasts, was correlated with the apoptotic
      index, as assessed with M30 cytoDeath immunohistochemistry, which is a good
      indicator of apoptotic events in the early-stage disease. CONCLUSIONS: The
      current results demonstrated that Mcl-1, as identified by a cyclic DNA array, may
      play a role in the pathogenesis of HMs and may have potential as a useful marker
      for predicting the clinical behavior of HMs.

PMID- 15578717
TI  - Nuclear or cytoplasmic expression of survivin: what is the significance?
AB  - Growing evidence suggests that survivin expression in cancer cell nuclei may
      represent an important prognostic marker to predict disease outcome for cancer
      patients. Current reports in this research area, however, are inconsistent and
      propose opposing conclusions regarding the significance and prognostic value of
      survivin nuclear expression. The aim of our study is to review and discuss the
      data reported in the original publications. We have also provided new
      experimental data to support our view regarding the possible reasons for the
      observed inconsistencies in the literature. This would alert researchers to pay
      attention to potential pitfalls in the determination of nuclear or cytoplasmic
      expression of survivin for the future.

PMID- 15578718
TI  - Postoperative radiotherapy for primary mucosal melanoma of the head and neck.
AB  - BACKGROUND: Primary head and neck mucosal melanoma (HNMM) has a poor prognosis
      with a low local control rate and frequent distant metastases. The objective of
      the current study was to determine the impact of postoperative radiotherapy on
      local control and survival. METHODS: One hundred forty-two patients with primary
      HNMM treated between 1979 and 1997 were reviewed. Of these, 69 patients with
      confirmed primary mucosal melanoma, absence of metastatic disease, and definitive
      management by surgery with or without postoperative radiotherapy and follow-up at
      the Institut Gustave-Roussy (Villejuif) were selected. The site of primary HNMM
      was sinonasal in 46 patients, oral in 19 patients, and pharyngolaryngeal in 4
      patients. Twenty-two patients (32%) had a locally advanced tumor (T3-T4) and 17
      patients had regional lymph node metastases after pathologic examination (pN >
      0). Thirty patients underwent surgery alone and 39 received postoperative
      radiotherapy. Patients with locally advanced tumors had received postoperative
      radiotherapy more frequently than those with small tumors (P = 0.02). RESULTS:
      Thirty-seven patients (54%) experienced local disease recurrence and 47 patients
      (68%) developed distant metastasis. The overall survival rates were 47% at 2
      years and 20% at 5 years. In the Cox multivariate analysis, patients with early T
      classification tumors who received postoperative radiotherapy had a better local
      disease-free survival (P = 0.004 and P = 0.05, respectively) compared with
      patients with late T-classification tumors who did not receive postoperative
      radiotherapy. Patients with advanced T-classification and pN > 0 stage had a
      shorter distant metastasis disease-free survival compared with patients with
      early T-classification and pN < 0 stage. Patients with advanced T-classification
      tumors had a shorter overall survival compared with patients with early T
      classification tumors (P = 0.003). CONCLUSIONS: The prognosis of patients with
      HNMM was poor. Patients had a high rate of distant metastasis and a low rate of
      local control. The current study suggested that postoperative radiotherapy
      increased local control even for patients with small tumors.

PMID- 15578719
TI  - Further evidence for a link between silica dust and esophageal cancer.
AB  - Our objective was to examine the relationship between silicosis and esophageal
      cancer in Hong Kong. The mortality of esophageal cancer was investigated among
      caisson and non-caisson workers in a cohort of 2,789 male silicotic workers in
      Hong Kong during the period 1981-99. The standardized mortality ratio (SMR) was
      calculated using the Hong Kong general population rates as reference. The
      indirect method proposed by Axelson was used to adjust for the confounding
      effects of cigarette smoking and alcohol drinking. The SMR of esophageal cancer
      in the entire cohort was 2.22 (95% CI 1.36-3.43, based on 20 deaths) and was 4.21
      (95% CI 1.81-8.30, based on 8 deaths) in the subgroup of caisson workers who had
      a higher exposure to silica dust. The relative risk of esophageal cancer for
      caisson silicotics was reduced to 2.34 after adjusting for the effects of smoking
      and alcohol drinking. No more excess risk of esophageal cancer was observed among
      non-caisson silicotic workers after the adjustments. This historical cohort study
      revealed that there was an increased mortality risk of esophageal cancer among
      silicotics who had worked in underground caissons in Hong Kong after adjusting
      for cigarette smoking and alcohol drinking. We believe that the excess risk of
      esophageal cancer mortality among caisson workers with silicosis could best be
      explained by the very heavy exposure to free silica dust in their working
      environment.

PMID- 15578720
TI  - TAp63gamma can substitute for p53 in inducing expression of the maspin tumor
      suppressor.
AB  - Maspin is a Class II tumor suppressor protein and plays a role in tumor growth by
      inhibiting cellular invasion and motility. It is a member of the serpin family of
      protease inhibitors and has been shown to reduce angiogenesis. Maspin gene
      expression can be upregulated by the tumor suppressor p53. We tested 7 p53
      related proteins of the p63 and p73 families for their ability to induce maspin
      expression. The p63 splice form TAp63gamma can substitute for p53 in activating
      the maspin promoter. TAp63gamma activates the promoter through the same consensus
      site as p53. In the DLD-1 colorectal adenocarcinoma cell line, harboring a tet
      off regulated transgene, induction of TAp63gamma leads to an upregulation of
      maspin mRNA from the chromosomal gene. With a short lag phase also maspin protein
      levels are elevated after induced TAp63gamma expression. To assess a potential
      function of p63-dependent maspin upregulation in tumors we followed expression of
      p53, p63 and maspin by immunohistochemistry in hepatocellular carcinomas. Two
      types of tumors with wild-type or mutant p53 were assayed. Interestingly, the
      majority of tumors expressing only a mutated and inactive p53 protein nonetheless
      stain positive for maspin, whereas these tumors were positive for p63 protein
      expression. In summary, we show that TAp63gamma can substitute for p53 in
      transcriptional activation of the maspin tumor suppressor gene. TAp63gamma
      employs the same DNA recognition site for this activation as p53. We observe
      expression patterns of p53, p63 and maspin proteins in tumor tissue that may
      indicate also a function of maspin induction by p63 in tumors.

PMID- 15578721
TI  - Monocarboxylate transporter expression in the spontaneous hypertensive rat:
      effect of stroke.
AB  - The expression of the monocarboxylate transporters (MCT) 1, 2, and 4 have been
      studied in the brains of spontaneous hypertensive (SH) rats after an ischemic
      insult induced by a permanent occlusion of the left middle cerebral artery
      (MCAO). Profound temporal changes in MCT1 expression were observed in various
      regions of the ipsilateral hemisphere over the period of 1 hr to 5 days after
      MCAO. Initially, a very rapid and transient increase in MCT1 mRNA was observed in
      neurons in the second layer of the cortex and in the piriform cortex at 1-3 hr. A
      slower but sustained increase in MCT1 mRNA expression was observed in astrocytes
      in the peri-infarct region beginning at 6 hr after MCAO and persisting over a
      period of 120 hr coinciding with their activation, migration, and involvement in
      scar formation. An increase in MCT1 expression in endothelial cells was seen over
      the same period. These increases in MCT1 expression in astrocytes and endothelial
      cells were accompanied by a corresponding increase in MCT1 protein. Finally at
      120 hr post-MCAO, increases in MCT1, MCT2, and MCT4 expression were observed in
      cells within the infarct and bordering the scar, the identity of which remains to
      be determined. Consistent with cell death, the levels of MCT1, MCT2, and MCT4
      mRNA decreased with cell death within the infarcted area but unlike MCT1, no
      increases in either MCT2 or 4 were observed within the remaining ipsilateral
      hemisphere. These studies reveal that the pattern of regulation of MCT1
      expression after MCAO is similar to that observed previously for glucose
      transporter 1 (GLUT1) and suggest that the regulation of MCT1 mRNA expression is
      mediated by the hypoxia-inducible transcription factor HIF1.

PMID- 15578722
TI  - Brain glucose concentrations in patients with type 1 diabetes and hypoglycemia
      unawareness.
AB  - Although it is well established that recurrent hypoglycemia leads to hypoglycemia
      unawareness, the mechanisms responsible for this are unknown. One hypothesis is
      that recurrent hypoglycemia alters brain glucose transport or metabolism. We
      measured steady-state brain glucose concentrations during a glucose clamp to
      determine whether subjects with type 1 diabetes and hypoglycemia unawareness may
      have altered cerebral glucose transport or metabolism after exposure to recurrent
      hypoglycemia. We compared 14 subjects with diabetes and hypoglycemia unawareness
      to 27 healthy control subjects. Brain glucose concentrations were measured under
      similar metabolic conditions using in vivo (1)H nuclear magnetic resonance (NMR)
      spectroscopy at 4 Tesla during a hyperglycemic clamp (plasma glucose = 16.7
      mmol/l) with somatostatin and insulin. Subjects with type 1 diabetes and
      hypoglycemia unawareness had significantly higher brain glucose concentrations
      compared to that in controls under the same conditions (5.5 +/- 0.3 vs. 4.7 +/-
      0.1 micromol/g wet weight, P = 0.016). These data suggest that changes in brain
      glucose transport or metabolism may occur as a result of recurrent hypoglycemia.

PMID- 15578723
TI  - Creatine enhances survival of glutamate-treated neuronal/glial cells, modulates
      Ras/NF-kappaB signaling, and increases the generation of reactive oxygen species.
AB  - The protective effects of creatine against glutamate cytotoxicity have been
      demonstrated in neuronal cells and animal models of neurodegenerative diseases.
      The mechanisms underlying creatine neuroprotection against glutamate-induced cell
      death are understood poorly. For the first time, we demonstrate a correlation
      between the protective effect of creatine and the modulation of Ras-mediated
      redox-dependent signaling pathways, which involve nuclear factor kappaB (NF
      kappaB) and reactive oxygen species (ROS). In primary cerebrocortical cultures of
      mixed neurons and glia, creatine significantly reduced glutamate-induced cell
      death. The increase in cell survival was accompanied by increased generation of
      oxygen radicals and decreased levels of farnesylated Ras and IkappaB, an
      inhibitor of NF-kappaB. Non-farnesylated Ras and ROS-dependent activation of NF
      kappaB have been shown to promote neuronal survival. Our data suggest that
      creatine may enhance survival signaling via activation of the Ras/NF-kappaB
      system. Possible mechanisms underlying the protective effect of creatine are
      discussed, including normalization of cellular GTP levels.

PMID- 15578724
TI  - Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a
      Greek population.
AB  - Epidemiological observations suggest that cancer arises from chronically inflamed
      tissues. Inflammatory bowel disease (IBD) is a typical example since patients
      with longstanding IBD are at increased risk for development of colorectal cancer
      (CRC). Therefore, genetic factors predisposing to or implicated in the chronic
      inflammatory process in IBD may simultaneously predispose to CRC. Recently
      CARD15/NOD2 has been associated with IBD, which further strengthens the notion
      that the inflammatory response plays a crucial role in this disease. Several
      mutations have been identified in the CARD15/NOD2 gene, which appear with
      significantly higher frequency in patients with IBD. In this report, we have
      examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the
      CARD2/NOD2 gene in a series of 104 consecutive Greek patients with sporadic
      colorectal cancer and 100 healthy individuals. The frequency of all the mutations
      was significantly elevated compared to the control population (R702W, OR=5.00,
      p=0.023; G908R, OR=2.78, p=0.025; 3020insC, OR=2.44, p=0.017). Patients with
      advanced stage tumors were more frequently carriers of at least 1 variant in the
      CARD15/NOD2 gene (p=0.009). Our results suggest that CARD2/NOD2 may be a genetic
      factor that predispose to sporadic colorectal cancer.

PMID- 15578725
TI  - Lack of association between chronic Chlamydophila pneumoniae infection and lung
      cancer among nonsmoking Chinese women in Singapore.

PMID- 15578726
TI  - Molecular basis of human glutamate dehydrogenase regulation under changing energy
      demands.
AB  - Glutamate dehydrogenase (GDH), an enzyme central to glutamate metabolism, is
      located in the mitochondria although there is evidence for extramitochondrial
      localization of GDH. In the human, housekeeping and nerve tissue-specific
      isoforms, encoded by the GLUD1 and GLUD2 genes, have been identified. The two
      isoenzymes differ markedly in their baseline activities, allosteric regulation,
      and thermal stability. GTP potently inhibits GLUD1-derived GDH (IC(50) = 0.2
      muM), whereas the GLUD2-derived isoenzyme is resistant to this compound. The
      GLUD2-derived GDH shows low basal activity and has the capacity to be activated
      fully by ADP or L-leucine. We used molecular biological tools to study the
      subcellular localization of GLUD1-derived GDH in cultured cells and the molecular
      basis of its regulation. COS7 cells, transfected with a GLUD1-pEGFP-N3 vector,
      revealed a GFP fluorescence pattern nearly identical to that of the mitochondrial
      marker pDsRed2-Mito. Site-directed mutagenesis of GLUD1 gene showed that
      replacement of Gly456 by Ala made the enzyme resistant to GTP (IC(50) = 2.8 +/-
      0.15 microM) without altering its regulation by ADP. Substitution of Ser for
      Arg443 rendered the enzyme virtually inactive at its basal state, but fully
      responsive to ADP activation. The Arg443Ser mutant was more active at pH 7.0 than
      at pH 8.0. The Gly456Ala change therefore dissociated GLUD2-derived GDH function
      from GTP, whereas the Arg443Ser change made enzyme regulation possible without
      this inhibitor. These properties may allow the brain isoenzyme to function well
      under conditions of intracellular acidification and increased turnover of ATP to
      ADP, as occurs in synaptic astrocytes during excitatory transmission.

PMID- 15578727
TI  - Astrocyte glycogen metabolism is required for neural activity during aglycemia or
      intense stimulation in mouse white matter.
AB  - We tested the hypothesis that inhibiting glycogen degradation accelerates
      compound action potential (CAP) failure in mouse optic nerve (MON) during
      aglycemia or high-intensity stimulation. Axon function was assessed as the evoked
      CAP, and glycogen content was measured biochemically. Isofagomine, a novel
      inhibitor of central nervous system (CNS) glycogen phosphorylase, significantly
      increased glycogen content under normoglycemic conditions. When MONs were bathed
      in artificial cerebrospinal fluid (aCSF) containing 10 mM glucose, the CAP failed
      16 min after exposure to glucose-free aCSF. MONs bathed in aCSF plus isofagomine
      displayed accelerated CAP failure on glucose removal. Similar results were
      obtained in MONs bathed in 30 mM glucose, which increased baseline glycogen
      concentration. The ability of isofagomine to increase glycogen content thus was
      not translated into delayed CAP failure. This is likely due to the inability of
      the tissue to metabolize glycogen in the presence of isofagomine, highlighting
      the importance of glycogen in sustaining neural function during aglycemia. The
      hypothesis that glycogen breakdown supports intense neural activity was tested by
      blocking glycogen breakdown during periods of high-frequency stimulation. The CAP
      area declined more rapidly when glycogen metabolism was inhibited by isofagomine,
      explicitly showing an important physiological role for glycogen metabolism during
      neural activity.

PMID- 15578728
TI  - Repeated injuries dramatically affect cells of the oligodendrocyte lineage:
      effects of PDGF and NT-3 in vitro.
AB  - In multiple sclerosis, relapses occur and remyelination is incomplete, whereas
      one demyelinating lesion induced by lysophosphatidyl choline (LPC) in rats is
      completely remyelinated; this process is accelerated by platelet-derived growth
      factor (PDGF) (Allamargot et al.: Brain Res 918:28-39,2001) and neurotrophin-3
      (NT-3) (Jean et al.: Brain Res 972:110-118,2003). Similarly, oligodendrocyte (OL)
      progenitors might not be depleted by two to three episodes of toxic demyelination
      (Penderis et al.: Brain 126:1382-1391,2003); nevertheless this does not allow
      conclusions about the fate of resident cells (mature OL). As myelinated fibers
      per OL are constantly decreased in chronic MS plaques (Fressinaud and Jean: J
      Neurochem 85(suppl):100, 2003), this suggests that OL decreased capability to
      synthesize new myelin membranes could result from successive relapses, impairing
      thereby remyelination. Thus, we have determined the consequences of multiple
      versus unique (Fressinaud and Vallat: J Neurosci Res 38:202-213, 1994) LPC
      treatments on newborn rat brain pure OL cultures, as well as the putative pro
      remyelinating effects of PDGF and of NT-3 in these conditions. Split (0.5. 0(-5)
      M, 6 h x 4) and multiple (2.10(-5) M, 24 h x 2) LPC doses induced more cell loss
      than a unique treatment (2 x 10(-5) M, 24 h) and there was no recovery. OL
      progenitors (A2B5+ cells) and differentiated (CNP+) OL were drastically
      decreased. Moreover, mature (MBP+) OL disappeared from these cultures, indicating
      that mature OL are also vulnerable to multiple insults. PDGF, as well as NT-3,
      induced at least partial recovery, and enhanced OL progenitor proliferation. In
      cultures treated with either of these growth factors, mature OL represented one
      fourth of cells and extended numerous ramified processes and putative myelin
      balls.

PMID- 15578729
TI  - Magnetization transfer studies of the fast and slow tissue water diffusion
      components in the human brain.
AB  - Magnetization transfer (MT) properties of the fast and slow diffusion components
      recently observed in the human brain were assessed experimentally. One set of
      experiments, performed at 1.5 T in healthy volunteers, was designed to determine
      whether the amplitudes of fast and slow diffusion components, differentiated on
      the basis of biexponential fits to signal decays over a wide range of b-factors,
      demonstrated a different or similar magnetization transfer ratio (MTR). Another
      set of experiments, performed at 3 T in healthy volunteers, was designed to
      determine whether MTRs differed when measured from high signal-to-noise images
      acquired with b-factor weightings of 350 vs 3500 s/mm2. The 3 T studies included
      measurements of MTR as a function of off-resonance frequency for the MT pulse at
      both low and high b-factors. The primary conclusion drawn from all the studies is
      that there appears to be no significant difference between the magnetization
      transfer properties of the fast and slow tissue water diffusion components. The
      conclusions do not lend support to a direct interpretation of the 'components' of
      the biexponential diffusion decay in terms of the 'compartments' associated with
      intra- and extracellular water.

PMID- 15578730
TI  - p16(INK4a) promoter methylation and protein expression in breast fibroadenoma and
      carcinoma.
AB  - The potential role of p16(INK4a) methylation in breast cancer is controversial
      whereas there are no data on fibroadenoma. To assess if inactivation of
      p16(INK4a) by promoter hypermethylation occurs in this hyperproliferative benign
      breast lesion or, on the contrary, it is strictly related to the carcinogenic
      process, we have tested the different histological components of 15 cases of
      fibroadenoma and the intraductal and infiltrating components of 15 cases of
      carcinoma and their adjacent non-tumoral epithelium. All samples were obtained by
      laser-assisted microdissection. The relationship between promoter methylation
      status, immunohistochemical protein expression and ki67 proliferative activity
      was evaluated for each lesion. Our data demonstrate that hypermethylation of
      p16(INK4a) promoter is a common event occurring at similar frequency in all the
      different histological areas of the benign and malignant breast lesions taken
      into exam. Conversely, protein p16 expression, although heterogeneously
      distributed within the section, is considerably higher in breast carcinoma as
      compared to fibroadenoma in both tumoral and non-tumoral epithelia and stroma.
      The protein localization was almost exclusively nuclear in fibroadenoma and non
      tumoral epithelia whereas, in carcinoma, the staining was both nuclear and
      cytoplasmic or cytoplasmic alone. Furthermore, in a subset of fibroadenoma with
      higher proliferative activity, p16 protein expression was substantially decreased
      as compared to those showing lower proliferation. We did not observe this
      association in carcinomas. Our data demonstrate that the hypermethylation of the
      p16(INK4a) promoter is not specifically associated with malignancy and that, on
      the contrary, the overexpression of p16 and its cytoplasmic sequestration is a
      feature of breast carcinoma.

PMID- 15578731
TI  - Brain iron uptake in hypotransferrinemic mice: influence of systemic iron status.
AB  - The relationship of the heterogeneity of iron concentrations in the brain with
      the regulation of iron uptake into specific brain regions remains unresolved. We
      used hypotransferrinemic mice and an iron-deficient or control diet to explore
      whether plasma transferrin (Tf), transferrin saturation, and plasma iron levels
      influence the uptake of (59)Fe and whether there was brain region specificity.
      Weaning wild-type (+/+) and heterozygotic mice (+/hpx), were sorted randomly to
      either a iron-deficient diet or a control iron diet for 8 weeks, whereas
      homozygous mice (hpx/hpx) ate the control diet for 8 weeks before (59)Fe uptake
      studies. Iron-deficient heterozygous and wild-type mice both had significantly
      greater plasma Tf levels (37.5 and 42.5 microM) than control mice had
      (heterozygous and wild-type controls were 20 and 32.5 microM) and far more than
      homozygous mice (<0.2 microM) had, thus providing five distinct levels of plasma
      Tf concentrations. After intravenous injection of (59)Fe, brains of iron
      deficient wild-type mice took up significantly more (59)Fe (0.15% dose) compared
      to control wild-type mice (0.056%) at 2 hr, a treatment effect that persisted
      through 24 hr. In contrast, diet had no effect in heterozygous mice. Importantly,
      homozygous mice had equivalent uptake to other groups (0.089% dose) by 24 hr.
      Early brain radioactivity varied by regions (hypothalamus and prefrontal cortex
      approximately 10-18% brain uptake > cerebellum, pons, thalamus, and striatum
      approximately 7-12% > cortex, hippocampus, and substantia nigra approximately 6
      8%). This distribution of radioactivity changed over 24 hr in the hypothalamus of
      heterozygous mice, homozygous mice, and iron-deficient wild-type mice. Homozygous
      mice also showed higher uptake (13-15%) in some regions (hypothalamus and
      cerebellum) than in other regions. In wild-type and heterozygous mice, (59)Fe
      uptake was inversely related to brain Tf and was independent of regional brain
      iron concentrations and plasma Tf levels or saturation. These experimental data
      suggest that brain iron uptake may be constitutive and independent of plasma Tf,
      transferrin saturation, or regional brain iron concentration. The proteins and
      mechanisms responsible for additional iron uptake into specific regions, or
      perhaps the redistribution are unclear though the data are supportive of a non
      transferrin-bound iron uptake pathway.

PMID- 15578732
TI  - Glutamate-mediated influx of extracellular Ca2+ is coupled with reactive oxygen
      species generation in cultured hippocampal neurons but not in astrocytes.
AB  - Generation of reactive oxygen species (ROS) in brain tissue leads to
      neurodegeneration. The major source of ROS is the mitochondrial respiratory
      chain. We studied regulation of Ca2+ level, mitochondrial potential, and ROS
      generation in defined mixed hippocampal cell cultures exposed to glutamate (100
      microM). Recordings were made from individually identified astrocytes and neurons
      to compare the physiologic responses in both cell types. Neurons identified by
      synaptotagmin immunoreactivity were characterized functionally by the fast Ca2+
      increase with K+ (50 mM) stimulation, and the astrocytes identified by glial
      fibrillary acidic protein (GFAP) staining had the functional characteristic of a
      transient Ca2+ peak in response to ATP (10 microM) stimulation. We found that the
      glutamate-mediated Ca2+ response in neurons is due largely to influx of
      extracellular Ca2+. This is consistent with our finding that in cultured
      hippocampal neurons, stores depending on the activity of the sarcoendoplasmic
      reticulum Ca2+ ATPase (SERCA) pump had a low Ca2+ content, regardless of whether
      the neurons were challenged or not with K+ before applying the SERCA inhibitor
      cyclopiazonic acid (CPA). Astrocytes displayed a large CPA-mediated Ca2 response,
      indicating a high level of Ca2+ load in the stores in astrocytes. Importantly,
      the rise in ROS generation due to glutamate application was cell-type specific.
      In neurons, glutamate induced a marked rise in generation of ROS, but not in
      astrocytes. In both astrocytes and neurons, the mitochondrial potential was
      increased in response to glutamate challenge. We conclude that in neurons, Ca2+
      influx accounts for the increased ROS generation in response to glutamate. This
      might explain the high vulnerability of neurons to glutamate challenge compared
      to the vulnerability of astrocytes. The high resistance of astrocytes is
      accompanied by an efficient downregulation of cytosolic Ca2+, which is not found
      in neurons.

PMID- 15578733
TI  - Activity of the lactate-alanine shuttle is independent of glutamate-glutamine
      cycle activity in cerebellar neuronal-astrocytic cultures.
AB  - The glutamate-glutamine cycle describes the neuronal release of glutamate into
      the synaptic cleft, astrocytic uptake, and conversion into glutamine, followed by
      release for use as a neuronal glutamate precursor. This only explains the fate of
      the carbon atoms, however, and not that of the ammonia. Recently, a role for
      alanine has been proposed in transfer of ammonia between glutamatergic neurons
      and astrocytes, denoted the lactate-alanine shuttle (Waagepetersen et al. [ 2000]
      J. Neurochem. 75:471-479). The role of alanine in this context has been studied
      further using cerebellar neuronal cultures and corresponding neuronal-astrocytic
      cocultures. A superfusion paradigm was used to induce repetitively vesicular
      glutamate release by N-methyl-D-aspartate (NMDA) in the neurons, allowing the
      relative activity dependency of the lactate-alanine shuttle to be assessed.
      [(15)N]Alanine (0.2 mM), [2-(15)N]/[5-(15)N]glutamine (0.25 mM), and
      [(15)N]ammonia (0.3 mM) were used as precursors and cell extracts were analyzed
      by mass spectrometry. Labeling from [(15)N]alanine in glutamine, aspartate, and
      glutamate in cerebellar cocultures was independent of depolarization of the
      neurons. Employing glutamine with the amino group labeled ([2-(15)N]glutamine) as
      the precursor, an activity-dependent increase in the labeling of both glutamate
      and aspartate (but not alanine) was observed in the cerebellar neurons. When the
      amide group of glutamine was labeled ([5-(15)N]glutamine), no labeling could be
      detected in the analyzed metabolites. Altogether, the results of this study
      support the existence of the lactate-alanine shuttle and the associated glutamate
      glutamine cycle. No direct coupling of the two shuttles was observed, however,
      and only the glutamate-glutamine cycle seemed activity dependent.

PMID- 15578734
TI  - Pharmacokinetics of a novel antiangiogenic agent KR-31831 in rats.
AB  - This study reports the absorption, dose-linearity and pharmacokinetics of a novel
      antiangiogenic agent KR-31831 in rats after i.v. and oral administration at doses
      of 5, 10 and 25 mg/kg on both occasions. Concentrations of KR-31831 were
      determined by a validated LC/MS/MS assay method. After i.v. injection, plasma
      concentration-time profiles showed multi-compartmental characteristics, and there
      were no significant differences in Cl (20.8-27.7 ml/min/kg) and dose-normalized
      AUC (178.1-231 microg x min/ml based on the 5 mg/kg dose) as a function of dose.
      However, Vss was significantly increased at the 25 mg/kg dose (4931 ml/kg)
      compared with those (2288-2421 ml/kg) at lower doses. Subsequently, t1/2 was
      increased from 143-159 min at the lower doses to 304 min at the 25 mg/kg dose.
      The altered VSS was found to be a result of reduced plasma protein binding at
      relatively high concentrations. Following oral administration (doses 5-25 mg/kg),
      the absolute oral bioavailability ranged from 37.8% to 46.3%, and there were no
      significant alterations in dose-normalized AUC, Tmax, Cmax and t1/2 as a function
      of dose. The extent of urinary excretion was low for both i.v. (0.35%-0.54%) and
      oral (0.13%-0.33%) doses. Further discussions on the chemical and microsomal
      stability were included. In conclusion, dose-independent absorption kinetics were
      observed at oral doses from 5 to 25 mg/kg in rats. Orally administered KR-31831
      could be eliminated mainly by the liver metabolic pathway.

PMID- 15578735
TI  - Ascertainment bias in linkage analysis: comments on Ginsburg et al.

PMID- 15578736
TI  - Selectfluor: mechanistic insight and applications.
AB  - The replacement of hydrogen atoms with fluorine substituents in organic
      substrates is of great interest in synthetic chemistry because of the strong
      electronegativity of fluorine and relatively small steric footprint of fluorine
      atoms. Many sources of nucleophilic fluorine are available for the derivatization
      of organic molecules under acidic, basic, and neutral conditions. However,
      electrophilic fluorination has historically required molecular fluorine, whose
      notorious toxicity and explosive tendencies limit its application in research.
      The necessity for an electrophilic fluorination reagent that is safe, stable,
      highly reactive, and amenable to industrial production as an alternative to very
      hazardous molecular fluorine was the inspiration for the discovery of
      selectfluor. This reagent is not only one of the most reactive electrophilic
      fluorinating reagents available, but it is also safe, nontoxic, and easy to
      handle. In this Review we document the many applications of selectfluor and
      discuss possible mechanistic pathways for its reaction.

PMID- 15578737
TI  - Design of a high-sensitivity negative ion source time-of-flight mass analyzer
      assembly created by cylindrical electrodes with a common axis.
AB  - The new design incorporates the negative ion source and the mass analyzer, both
      constructed from cylindrical electrodes. The ion source is formed by three
      gridded cylindrical electrodes: a pulsed grid, the intermediate grid and the
      final accelerating grid. During a first time lapse, the electrons penetrate
      through the pulsed grid into the retarding field between this grid and the
      intermediate grid. The electrons are turning at some depth inside this intergrid
      space, where the attachment to neutral molecules most probably occurs. Next, the
      pulsed grid becoming strongly negative and ions are extracted towards the final
      acceleration grid. The ions from the cylindrical surface where they were created
      concentrate on the common axis of the electrodes (lateral focusing). The source
      lateral and time focus are coincident. A cylindrical electrostatic mirror is
      fitted to the source. The design, with a single stage, ensures also lateral
      focusing of the ions diverging from the common axis of the electrodes. The mirror
      electric and geometric parameters were selected to ensure both lateral and time
      focusing on the final detector with subsequent high luminosity. The basic
      parameters of the specific negative ion source time-of-flight mass analyzer
      design proposed here, are ion source final acceleration, intermediate, pulsed
      cylindrical grid radii 10, 20 and 30 mm, respectively, electrostatic mirror
      earthed grid and ion turning points surface radii 0.6 and 0.8 m, respectively.
      Ion packet smearing by the ion energy spread (resulting from the initial electron
      energy spread as electrons are turning at different depths inside the ionization
      region, from the moment when ions were created, being accelerated towards the
      pulsed grid during ionization) and by the turnaround time inside the cylindrical
      field was accounted for. Maintaining very high sensitivity, a resolution of the
      order of 100 is expected.

PMID- 15578738
TI  - Fragmentation studies on the antibiotic avilamycin A using ion trap mass
      spectrometry.
AB  - A comprehensive study on the fragmentation pattern of the antimicrobial growth
      promoter avilamycin A was conducted in a quadrupole ion trap mass spectrometer
      equipped with an electrospray ionization (ESI) source. Performing multiple-stage
      experiments on the deprotonated molecule (m/z 1401) and its principal product
      ions showed that a sequential shortening of the oligosaccharide backbone took
      place, which can be attributed to the localization of the negative charge in the
      terminal dichloroisoeverninic acid. Under (+)-ESI conditions, avilamycin A
      readily formed an intense sodium-cationized molecule, [M + Na](+) (m/z 1425).
      Structural elucidation of the second-, third- and fourth-generation fragment ions
      revealed that all of the structures shared a common molecular portion comprising
      a central monosaccharide. This observation allowed us to assign confidently the
      complexation site of the alkali metal cation. In addition to the monosodiated
      molecule, the full-scan mass spectral acquisition also yielded a less abundant
      disodiated molecule, [M - H + 2Na](+) (m/z 1447). Multiple-stage experiments on
      this ion indicated that the second sodium ion compensates for the negative charge
      located at either of two positions within the molecule. While deprotonation of
      the phenolic hydroxyl group in the dichloroisoeverninic acid moiety was suggested
      to be driven by charge stabilization in the aromatic ring (in analogy with the
      deprotonated molecule in the (-)-ESI mode), the deprotonation at an alpha-carbon
      of an ester side-chain substituent in the oligosaccharide part was believed to
      provide a stable chelation-like coordination site for the cation.

PMID- 15578739
TI  - Role of recombination in evolution of enteroviruses.
AB  - Enteroviruses, members of the Picornaviridae family, comprise a large (over 70
      serotypes) group of viruses that are ubiquitous in nature, infect different
      species and cause a wide range of diseases. Human enteroviruses were recently
      classified into five species, human enterovirus A-D and poliovirus. Recombination
      has long been known to be an important property of poliovirus genetics. Recently,
      several publications demonstrated that recombination is extremely frequent also
      in non-polio enteroviruses, and allows independent evolution of enterovirus
      genome fragments even on a microevolutionary scale. Prototype enterovirus strains
      were shown to have complex phylogenetic relations, and almost all modern
      enterovirus isolates turned out to be recombinants compared with the prototype
      strains. Recombination takes place strictly between members of the same species,
      and usually spares the capsid-encoding genome region. Therefore, it can be
      concluded that the enterovirus species exist as a worldwide reservoir of genetic
      material comprising a limited quantity of capsid gene sets defining a finite
      number of serotypes and a range of non-structural genes that recombine frequently
      to produce new virus variants. This new model of enterovirus genetics helps to
      explain the failure of previous attempts to connect serotype and disease profile
      in non-polio enteroviruses, and seriously questions existing typing approaches
      that are based solely on the capsid-encoding genome region. It remains to be
      determined what role recombination plays in the emergence of new enterovirus
      variants and in the macroevolution of animal enteroviruses and viruses of the
      picorna-like supergroup.

PMID- 15578740
TI  - Profiling histidine-containing dipeptides in rat tissues by liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - The histidine-containing dipeptides carnosine (CAR) and structurally related
      anserine (ANS) and homocarnosine (HCAR), widely distributed in vertebrate
      organisms, have recently been proposed as endogenous quenchers for highly
      cytotoxic alpha,beta-unsaturated aldehydes generated by peroxidation. A
      sensitive, selective, specific and rapid liquid chromatographic/electrospray
      ionization tandem mass spectrometric assay was developed and validated for the
      simultaneous determination of these peptides in biological matrices in order to
      establish their plasma/tissue distribution. Samples (plasma or tissue homogenates
      from male rats) were prepared by protein precipitation with HClO(4) (1 : 1, v/v)
      containing H-Tyr-His-OH as internal standard. The supernatant was separated on a
      Phenomenex Sinergy polar-RP column with a mobile phase of water-acetonitrile
      heptafluorobutyric acid (9 : 1 : 0.01, v/v/v) at a flow-rate of 0.2 ml min(-1),
      with a run time of 10 min. Detection was effected on an ion trap mass
      spectrometer equipped with an electrospray ionization interface operating in
      positive ionization mode. The acquisitions were in the multiple reaction
      monitoring mode using the following precursor --> product ion combinations: H-Tyr
      His-OH (internal standard) m/z 319 --> 301; CAR m/z 227 --> 210 + 209; ANS m/z
      241 --> 224 + 197 + 170; HCAR m/z 241 --> 156. The method was validated over the
      concentration range 15-1000 nmol g(-1) and the limit of quantification (LOQ) and
      limit of detection (LOD) were 12.5 and 4.2 pmol injected, respectively. The intra
      and inter-day precisions were <10% (< or =17.47% at the LOQ) and the intra- and
      inter-assay accuracies were within +/-10% for all concentrations. The mapping
      profile in rat tissue gave the following results: the highest concentrations of
      CAR and ANS were found in skeletal muscles (soleus, gastrocnemius, tibialis),
      followed by the heart, cerebellum and brain (ANS below the LOQ). HCAR was found
      only in the brain and cerebellum. No histidine-containing dipeptides were
      detectable in plasma, liver, kidney and lung.

PMID- 15578741
TI  - Identification of proteins by combination of size-exclusion chromatography with
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and
      comparison of some desalting procedures for both intact proteins and their
      tryptic digests.
AB  - Separation of a protein mixture by size-exclusion chromatography (SEC) was
      combined with matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS). Identification of proteins in the collected fractions
      was performed both as intact proteins by MALDI-TOFMS and using peptide mass
      fingerprinting (PMF) after their digestion with trypsin. The presence of salts
      mostly disturbs the MALDI-TOFMS signal and, therefore, proper purification or
      desalting procedures must be employed. Four desalting procedures (desalting
      column packed with Sephadex G-100, on-target washing, centrifugal filter devices
      and ZipTip C(18)) for purification of fractions of proteins separated by SEC and
      their tryptic digests prior to determination of their exact molecular masses by
      MALDI-TOFMS were compared. In the case of intact proteins, the experiments showed
      that the best desalting procedures are the use of ZipTip C(18) pipette tips and
      Ultrafree CL centrifugal filter devices. The peptide digests can be purified by
      using ZipTip C(18) pipette tips or on-target washing when both of these
      procedures provide similar results. On-target washing can be used as a simple
      procedure to improve the mass spectra of salt-containing samples. Analyses of the
      droplets collected after the on-target washing show losses of sample and matrix
      caused by dissolution of these compounds during this procedure. Further, it was
      found that protein identification based on PMF is more sensitive than analyses of
      intact proteins and that multiple on-target washing is very advantageous for
      analyses of peptide mixtures with a high content of salts.

PMID- 15578742
TI  - Exact molecular mass determination of various forms of native and de-N
      glycosylated human plasma-derived antithrombin by means of electrospray
      ionization ion trap mass spectrometry.
AB  - Human plasma-derived antithrombin was characterized in both the native and de-N
      glycosylated forms (without separation of isoforms) by means of electrospray
      ionization ion trap mass spectrometry (ESI-ITMS). In order to determine the
      limits of the instrument set-up, the molecular mass precision and accuracy of the
      ESI-ITMS analysis was evaluated with the standard protein enolase and some
      instrumental data acquisition parameters were optimized. Mass precision was
      determined as a function of the number of averaged mass spectra (= scans) and
      data acquisition time. For this study, 20 and 50 scans were averaged and the data
      acquisition time was chosen to be between 0.5 and 5 min. It turned out that data
      acquisition times longer than approximately 2 min show no significant differences
      of the standard deviation of the determined molecular mass. Furthermore, the ion
      trap scan rate was varied at constant acquisition time of 2 min and the number of
      averaged scans was set to 20. At the scan rate of 13,000 u s(-1) a mass precision
      of +/-1.8 Da and a mass accuracy of +0.026% were determined. On reducing the scan
      rate to 5500 u s(-1), better agreement with the theoretical molecular mass was
      obtained, showing a mass accuracy of +0.012% but with a decrease in the mass
      precision to +/-3.0 Da. Using the optimized scan rate of 13,000 u s(-1) and a
      data acquisition time of 2 min, the exact molecular mass was determined of the
      three forms of antithrombin, namely the alpha-form, the beta-form and the natural
      mixture (present in human plasma) containing both forms. The protonated molecular
      masses were found to be 57,854 and 55,664 Da for the affinity chromatography
      isolated alpha-and beta-form, respectively. The mass difference of 2190 Da is
      attributed to the known difference in carbohydrate content at one specific site.
      The protonated molecular mass of the dominating species of the natural mixture in
      human plasma was shown to be 57,850 Da, corresponding to the alpha-form, the
      major component in native plasma. In this mixture the beta-form was also
      detected, exhibiting a protonated molecular mass of 55,655 Da, but showing a much
      lower abundance, as expected. To obtain a complete release of the N-glycan
      residues by means of PNGase F, a denaturation, reduction and alkylation step of
      the glycoproteins was performed before the enzymatic reaction. After enzymatic
      removal of all N-glycans, the protonated molecular masses obtained were 49,399,
      49,380 and 49,391 Da for the alpha-form, the beta-form and the unseparated
      natural mixture, respectively. These values are in good agreement (+0.026% for
      the alpha-form, -0.012% for the beta-form and +0.010% for the unseparated
      mixture) with the calculated molecular mass based on the SwissProt data. The
      determined molecular masses after reduction/alkylation and de-N-glycosylation of
      the alpha-and beta-forms are almost equal, indicating that no major differences
      exist between the three preparations on the amino acid level.

PMID- 15578743
TI  - Characterization of the disulfides of bio-thiols by electrospray ionization and
      triple-quadrupole tandem mass spectrometry.
AB  - Glutathione and other intracellular low molecular mass thiols act both as the
      major endogenous antioxidant and redox buffer system and, as recently
      highlighted, as an important regulator of cellular homeostasis. Such cellular
      functions are mediated by protein thiolation, a newly recognized post
      translational modification which involves the formation of mixed disulfides
      between GSH and key disulfide-linked Cys residues in the native protein
      structure. It is also well known that thiol-seeking heavy metals, such as
      mercury, cadmium and lead, may interfere in this regulatory system, thus
      disrupting the cellular functioning. To identify such mixed disulfides in order
      to investigate their biological role, 15 homo- and heterodimeric disulfides were
      prepared by air oxidation of binary mixtures containing cysteine, homocysteine,
      penicillamine, N-acetylcysteine, N-acetylpenicillamine and glutathione and their
      protonated molecules were characterized by mass spectrometry. Collisionally
      activated unimolecular decomposition of protonated homo- and heterodimeric
      disulfides generated by electrospray ionization gives rise to fission of the
      disulfide system both between the two sulfur atoms and across the C--S bonds, to
      yield structurally specific fragments which allow one to define the structure of
      the compounds and to discriminate between isomeric compounds. Fission between the
      sulfur atoms yields a pair of R--S(+) ions and, in some cases, also the
      complementary fragments corresponding to the protonated amino acids. Fission
      across the C--S bonds mainly occurs in the disulfides of N-acetylcysteine and N
      acetylpenicillamine and gives rise to non-S-containing fragments formally similar
      to those obtained from some mercapturic acids. The complementary fragments,
      formally connected as R--S--S(+) ions are also observed. Fragmentation of
      glutathione disulfides mainly shows the characteristic loss of the terminal gamma
      linked glutamic acid and little, if any, fragmentation of the disulfide system.

PMID- 15578744
TI  - Using mass spectrometry to probe the subtle differences in conformations of
      several cytochromes c in aqueous and methanol solutions.
AB  - We have detected, using electrospray mass spectrometry, minor changes in the H/D
      exchange rates in various solvents for cytochromes c obtained from five different
      species. We compared the exchange rates exhibited by these proteins by mixing
      horse cytochrome c with each of the other four species and monitoring their
      exchanges simultaneously by mass spectrometry. The use of horse cytochrome c as a
      reference allowed us to make very accurate comparisons of the small differences
      in hydrogen exchange rates among the various species. The exchange experiments
      were performed in water and methanol at several concentrations in an effort to
      determine whether the cytochromes c of these five species have different
      conformations in specific solvents, which would cause their exchange rates to
      differ. Therefore, monitoring the level of exchange as a function of time in both
      water and water-methanol mixtures is a method for detecting subtle structural
      changes of proteins in their native or unfolded intermediate states.

PMID- 15578746
TI  - Matrix-assisted laser desorption/ionization mass spectrometry for the
      characterization of ionic liquids and the analysis of amino acids, peptides and
      proteins in ionic liquids.
AB  - Ionic liquids are interesting solvents for a number of applications in chemistry
      and biotechnology. We characterized five different ionic liquids by laser
      desorption/ionization (LDI) and by matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry (MS) and studied the analysis of amino acids, peptides
      and proteins dissolved in these solvents. Signals of both anions and cations of
      the ionic liquids could be observed both in LDI- and in MALDI-MS. In the latter
      case, adduct formation between anions and cations of the analytes was observed.
      Amino acids, peptides and proteins could be analyzed in ionic liquids after
      addition of matrix substances. Sodium and potassium adducts were not observed in
      any analysis involving ionic liquids. Low molecular mass compounds and peptides
      could be analyzed best in the presence of water-immiscible ionic liquids, whereas
      proteins gave the best results in water-miscible ionic liquids. Optimal analysis
      conditions such as molar matrix-to-analyte and ionic liquid-to-matrix ratios were
      determined. Homogeneity of samples in the presence of ionic liquids was reduced
      compared with classical MALDI preparations. Relative quantitation of amino acids
      was possible using isotope-labeled internal standards. MALDI-MS thus can be used
      for the analysis of chemical reactions and the screening of enzyme-catalyzed
      reactions in ionic liquids and for the analysis of the biocatalysts dissolved in
      these solvents. Theoretical aspects of ion formation in the presence of ionic
      liquids both in LDI and MALDI analysis are discussed.

PMID- 15578747
TI  - Regional phospholipid analysis of porcine lens membranes by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - The applicability of matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOFMS) to the qualitative and quantitative analysis of
      most mammalian phospholipid (PL) classes was demonstrated in a crude extract of
      porcine lens membranes. When 2,5-dihydroxybenzoic acid (DHB) was used as the
      matrix, positive-ion spectra allowed the accurate quantification of
      phosphatidylcholines (PCs) and sphingomyelins (SMs). Other PLs such as
      phosphatidylethanolamines (PEs), phosphatidylethanolamine plasmalogens (PEps),
      phosphatidylethanolamine ethers (PEes) and phosphatidylserines (PSs), could also
      be detected, but their lower ionization efficiency led to negative errors in
      their quantification. Despite this limitation, it was possible to determine
      relative changes among PLs extracted from cortical and nuclear regions. Negative
      ion spectra were acquired with the use of p-nitroaniline (PNA) as the matrix.
      Because neither PCs nor SMs produce negative ions, other PL classes can be
      analyzed selectively. The absolute quantification of the various PL classes
      detectable in negative-ion spectra was also affected by differences in ionization
      efficiencies. However, the trends in compositional changes between cortical and
      nuclear-fiber PLs were in agreement with those obtained by (31)P NMR
      spectroscopy. MALDI-TOFMS also offers the possibility of studying variations in
      the acyl-chain distribution of the various species comprising each PL class. For
      porcine lenses, PCs, PEs and phosphatidylinositols (PIs) exhibited the greatest
      depletions in going from cortical to nuclear membranes. Among their individual
      species, those with two or more sites of unsaturation suffered the most
      significant reduction.

PMID- 15578748
TI  - A simple and sensitive assay for the quantitative analysis of paclitaxel in human
      and mouse plasma and brain tumor tissue using coupled liquid chromatography and
      tandem mass spectrometry.
AB  - The development and validation of an assay for the determination of paclitaxel in
      human plasma, human brain tumor tissue, mouse plasma and mouse brain tumor tissue
      is described. Paclitaxel was extracted from the matrices using liquid-liquid
      extraction with tert-butyl methyl ether, followed by chromatographic analysis
      using an alkaline eluent. Positive ionization electrospray tandem mass
      spectrometry was performed for selective and sensitive detection. The method was
      validated according to the FDA guidelines on bioanalytical method validation.
      Validation results indicate that calibration standards in human plasma can be
      used to quantify paclitaxel in all tested matrices. In human samples, the
      validated range for paclitaxel was from 0.25-1000 ng ml(-1) using 200 microl
      plasma aliquots and from 5 to 5000 ng g(-1) using 50 microl tumor homogenate
      aliquots (0.2 g tissue ml(-1) control human plasma). In mice, the ranges were 1
      1000 ng ml(-1) and 5-5000 ng g(-1) using 50 microl of mouse plasma and 50 microl
      of tumor homogenate aliquots (0.2 g tissue ml(-1) control human plasma),
      respectively. The method can be applied to studies generating only small sample
      volumes (e.g. mouse plasma and tumor tissue), but also to studies in human plasma
      requiring a lower limit of quantitation. The assay was applied successfully to
      several studies with both human and mouse samples.

PMID- 15578749
TI  - Rodent pharmacokinetics and receptor occupancy of the GABAA receptor subtype
      selective benzodiazepine site ligand L-838417.
AB  - The pharmacokinetics of L-838417, a GABAA receptor subtype selective
      benzodiazepine site agonist, were studied in rats and mice after single oral
      (p.o.), intraperitoneal (i.p.) and intravenous (i.v.) doses. In both species L
      838417 was well absorbed following i.p. administration and whilst in rats p.o.
      bioavailability was good (41%), in mice it was negligible (<1%), precluding this
      as a route of administration for mouse behavioural studies. Despite having a
      similar volume of distribution (ca 1.4 l/kg) in rats and mice, L-838417 was
      cleared at twice liver blood flow in mice (161 ml/min/kg) and moderately cleared
      in rats (24 ml/min/kg), potentially explaining the poor oral bioavailability in
      mice. Finally, as a pharmacodynamic readout the benzodiazepine binding site
      occupancy was determined in rats (0.3-3 mg/kg, p.o.) and mice (1-30 mg/kg, i.p.)
      using a [3H]Ro 15-1788 in vivo binding assay. Although the resulting dose
      occupancy relationship for both species demonstrated a dose-dependent increase in
      receptor occupancy, appreciable variability was observed at low dose levels,
      potentially making interpretation of behavioural responses difficult. In
      contrast, a clear relationship between plasma and brain concentrations and
      receptor occupancy were determined suggesting the observed dose-occupancy
      variability is a consequence of the pharmacokinetic properties of L-838417. The
      plasma and brain concentrations required to occupy 50% of the benzodiazepine
      binding sites were similar in both rats (28 ng/ml and 33 ng/ml g, respectively)
      and mice (63 ng/ml and 53 ng/ml g, respectively), with a non-linear concentration
      response observed with increasing doses of L-838417. These studies demonstrate
      the importance of utilizing pharmacokinetic/receptor occupancy data when
      interpreting pharmacodynamic responses at a given dose.

PMID- 15578751
TI  - Case-control single-marker and haplotypic association analysis of pedigree data.
AB  - Related individuals collected for use in linkage studies may be used in case
      control linkage disequilibrium analysis, provided one takes into account
      correlations between individuals due to identity-by-descent (IBD) sharing. We
      account for these correlations by calculating a weight for each individual. The
      weights are used in constructing a composite likelihood, which is maximized
      iteratively to form likelihood ratio tests for single-marker and haplotypic
      associations. The method scales well with increasing pedigree size and
      complexity, and is applicable to both autosomal and X chromosomes. We apply the
      approach to an analysis of association between type 2 diabetes and single
      nucleotide polymorphism markers in the PPAR-gamma gene. Simulated data are used
      to check validity of the test and examine power. Analysis of related cases has
      better power than analysis of population-based cases because of the increased
      frequencies of disease-susceptibility alleles in pedigrees with multiple cases
      compared to the frequencies of these alleles in population-based cases. Also,
      utilizing all cases in a pedigree rather than just one per pedigree improves
      power by increasing the effective sample size. We demonstrate that our method has
      power at least as great as that of several competing methods, while offering
      advantages in the ability to handle missing data and perform haplotypic analysis.

PMID- 15578752
TI  - Use of MMSE to differentiate Alzheimer's disease from dementia with Lewy bodies-
      response to Larner.

PMID- 15578753
TI  - Current awareness in geriatric psychiatry.

PMID- 15578754
TI  - High-throughput assay of rotenone in olive oil using atmospheric pressure
      chemical ionization tandem mass spectrometry.
AB  - A high-throughput method is presented for the determination of rotenone in
      contaminated matrices. The procedure involves atmospheric pressure chemical
      ionization tandem mass spectrometry with a triple-quadrupole instrument and the
      use as internal standard of a cycloadduct derivative of rotenone itself. The
      method was applied to the evaluation of the decay of rotenone in olives and olive
      oil at various times after exposure to the contaminant.

PMID- 15578755
TI  - Tandem mass spectrometric data-FAAH inhibitory activity relationships of some
      carbamic acid O-aryl esters.
AB  - We have recently described a class of systemically active inhibitors of the
      intracellular activity of fatty acid amide hydrolase (FAAH) and traced extensive
      structure-activity relationships. These compounds, characterized by an N-alkyl
      carbamic acid O-aryl ester structure, exert potent anxiolytic-like effects in
      animal models. In the present study, possible relationships between mass
      spectrometric parameters (related to the propensity of the C(O)--O bond to be
      cleaved) and FAAH-inhibitory potency were tested. With this aim, a set of our
      products was analyzed by electrospray ionization mass spectrometry and the
      protonated molecules were decomposed by low-energy collisions. The experiments
      were performed by ion trap mass spectrometry, which led to a step-by-step energy
      deposition, thus favouring the lowest critical energy decomposition channels. For
      all compounds, breakdown curves relative to [MH](+) ions and to the fragment
      implying C(O)--O bond cleavage were obtained. The crossing point between these
      curves was related to the energetics of decomposition and the values found for
      the investigated compounds were linearly correlated (r(2) = 0.797) with their
      FAAH-inhibitory activity. This indicates that the energetics of the C(O)--O bond
      cleavage may be relevant in explaining FAAH inhibition.

PMID- 15578756
TI  - Study of the reaction products of flavonols with 2,2-diphenyl-1-picrylhydrazyl
      using liquid chromatography coupled with negative electrospray ionization tandem
      mass spectrometry.
AB  - The products obtained after the reaction between flavonols and the stable free
      radical 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) in both methanol and acetonitrile
      were characterized using liquid chromatography coupled with negative electrospray
      ionization tandem mass spectrometry (LC/ESI-MS/MS) and NMR spectroscopy. The
      flavonols studied were quercetin, kaempferol and myricetin. In methanol, two
      reaction products of oxidized quercetin were identified using LC/ESI-MS/MS and
      NMR. Quercetin was oxidized through a transfer of two H-atoms to DPPH(*) and
      subsequently incorporated either two CH(3)OH molecules or one CH(3)OH- and one
      H(2)O molecule giving the products 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3
      dimethoxy-2,3-dihydrochromen-4-one and 2-(3,4-dihydroxyphenyl)-3,3,5,7
      tetrahydroxy-2-methoxy-2,3-dihydrochromen-4-one, respectively. LC/ESI-MS/MS
      analysis revealed that in methanol, kaempferol and myricetin also gave rise to
      methoxylated oxidation products similar to that identified for quercetin.
      Kaempferol, in addition, also exhibited products where a kaempferol radical,
      obtained by a transfer of one H-atom to DPPH(*), reacted with CH(3)OH through the
      addition of CH(3)O(*), yielding two isomeric products. When the reaction took
      place in acetonitrile, LC/ESI-MS/MS analysis showed that both quercetin and
      myricetin formed stable isomeric quinone products obtained by a transfer of two H
      atoms to DPPH(*). In contrast, kaempferol formed two isomeric products where a
      kaempferol radical reacted with H(2)O through the addition of OH(*), i.e. similar
      to the reaction of kaempferol radicals with CH(3)OH.

PMID- 15578757
TI  - Electrospray ionization ion-trap multistage mass spectrometric study of sodium
      cationized aldobiuronic and pseudoaldobiuronic acid derivatives.
AB  - Fragmentation mechanisms of electrospray ionization (ESI) mass spectrometry of
      aldobiuronic and pseudoaldobiuronic acid derivatives were elucidated by
      multistage mass spectrometric (MS(n), n = 2-5) measurements of selected ions.
      Characteristic under the conditions of ESI-MS analysis is the production of
      alkali metal (Na and K) cationized adducts. The probability the of locations of
      Na cations in per-O-methylated compounds was proved by quantum chemical
      calculations, using the Jaguar program. The most probably position of alkali
      metal attachment is the carboxy group of the methoxycarbonyl C-5 group of the
      uronic acid unit. Characteristic cleavages vary according the kind of O
      derivatization. In most cases they take place on the acidic part of the dimer and
      at the interglycosidic oxygen atom. As a result, the criteria for the
      differentiation of aldobiouronic and pseudoaldobiouronic acids derivatives were
      elucidated.

PMID- 15578758
TI  - Characterization of covalently inhibited extracellular lipase from Streptomyces
      rimosus by matrix-assisted laser desorption/ionization time-of-flight and matrix
      assisted laser desorption/ionization quadrupole ion trap reflectron time-of
      flight mass spectrometry: localization of the active site serine.
AB  - A chemical modification approach combined with matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry was used to identify the active
      site serine residue of an extracellular lipase from Streptomyces rimosus R6-554W.
      The lipase, purified from a high-level overexpressing strain, was covalently
      modified by incubation with 3,4-dichloroisocoumarin, a general mechanism-based
      serine protease inhibitor. MALDI time-of-flight (TOF) mass spectrometry was used
      to probe the nature of the intact inhibitor-modified lipase and to clarify the
      mechanism of lipase inhibition by 3,4-dichloroisocoumarin. The stoichiometry of
      the inhibition reaction revealed that specifically one molecule of inhibitor was
      bound to the lipase. The MALDI matrix 2,6-dihydroxyacetophenone facilitated the
      formation of highly abundant [M + 2H](2+) ions with good resolution compared to
      other matrices in a linear TOF instrument. This allowed the detection of two
      different inhibitor-modified lipase species. Exact localization of the modified
      amino acid residue was accomplished by tryptic digestion followed by low-energy
      collision-induced dissociation peptide sequencing of the detected 2
      (carboxychloromethyl)benzoylated peptide by means of a MALDI quadrupole ion trap
      reflectron TOF instrument. The high sequence coverage obtained by this approach
      allowed the confirmation of the site specificity of the inhibition reaction and
      the unambiguous identification of the serine at position 10 as the nucleophilic
      amino acid residue in the active site of the enzyme. This result is in agreement
      with the previously obtained data from multiple sequence alignment of S. rimosus
      lipase with different esterases, which indicated that this enzyme exhibits a
      characteristic Gly-Asp-Ser-(Leu) motif located close to the N-terminus and is
      harboring the catalytically active serine residue. Therefore, this study
      experimentally proves the classification of the S. rimosus lipase as GDS(L)
      lipolytic enzyme.

PMID- 15578759
TI  - Microextraction in packed syringe (MEPS) for liquid and gas chromatographic
      applications. Part II--Determination of ropivacaine and its metabolites in human
      plasma samples using MEPS with liquid chromatography/tandem mass spectrometry.
AB  - A new technique for sample preparation on-line with liquid chromatographic/tandem
      mass spectrometric (LC/MS/MS) assay was developed. Microextraction in a packed
      syringe (MEPS) is a new miniaturized, solid-phase extraction technique that can
      be connected on-line to gas or liquid chromatography without any modifications.
      In MEPS approximately 1 mg of the solid packing material is inserted into a
      syringe (100-250 microl) as a plug. Sample preparation takes place on the packed
      bed. The bed can be coated to provide selective and suitable sampling conditions.
      The new method is very promising, very easy to use, fully automated, of low cost
      and rapid in comparison with previously used methods. This paper presents the
      development and validation of a method for MEPS on-line with LC/MS/MS.
      Ropivacaine and its metabolites (PPX and 3-OH-ropivacaine) in human plasma
      samples were used as model substances. The method was validated and the
      calibration curves were evaluated by means of quadratic regression and weighted
      by the inverse of the concentration, 1/x, for the calibration range 2-2000 nM.
      The applied polymer could be used more than 100 times before the syringe was
      discarded. The extraction recovery was between 40 and 60%. The results showed
      high correlation coefficients (R(2) > 0.999) for all analytes in the calibration
      range studied. The accuracy, expressed as a percentage variation from the nominal
      concentration values, ranged from 0 to 6%. The precision, expressed as the
      relative standard deviation, at three different concentrations (quality control
      samples) was consistently about 2-10%. The limit of quantification was 2 nM.

PMID- 15578760
TI  - Direct catalytic enantioselective alpha-aminomethylation of ketones.

PMID- 15578761
TI  - Direct amino acid catalyzed asymmetric alpha oxidation of ketones with molecular
      oxygen.

PMID- 15578762
TI  - Highly compatible metal and enzyme catalysts for efficient dynamic kinetic
      resolution of alcohols at ambient temperature.

PMID- 15578763
TI  - Continuous two-channel time-of-flight mass spectrometric detection of
      electrosprayed ions.

PMID- 15578764
TI  - Gold catalysis: the benefits of N and N,O ligands.

PMID- 15578766
TI  - [Ga22(PtBu2)12]: diversity in the arrangement of 22 gallium atoms--a unique case
      in the field of metalloid clusters?

PMID- 15578765
TI  - Formation of 1,4-diketones by aerobic oxidative C-C coupling of styrene with 1,3
      dicarbonyl compounds.

PMID- 15578768
TI  - Bioequivalence assessment of Lovrak (Julphar, UAE) compared with Zovirax (Glaxo
      Wellcome, UK)--Two brands of Acyclovir--in healthy human volunteers.
AB  - Two studies were performed to assess the relative bioavailability of Lovrak
      (Julphar, UAE) compared with Zovirax (Glaxo Wellcome, UK) at the International
      Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved
      acyclovir tablets and the other acyclovir suspension. Each study enrolled 24
      volunteers and in both studies, after an overnight fasting, the two brands of
      acyclovir were administered as a single dose on 2 treatment days separated by 1
      week washout period. After dosing, serial blood samples were collected for a
      period of 16 h. Plasma harvested from blood, was analysed for acyclovir by an
      HPLC method with UV detection. Various pharmacokinetic parameters including AUC0
      t, AUC0-infinity, Cmax, Tmax, T1/2 and Kelm were determined from plasma
      concentrations for both formulations and found to be in good agreement with the
      reported values. AUC0-t, AUC(0-proportional to), and Cmax were tested for
      bioequivalence after log-transformation of data. No significant difference was
      found based on ANOVA; 90% confidence intervals for the test/reference ratio of
      these parameters were found within the bioequivalence acceptance range 80%-125%.
      Based on these statistical inferences it was concluded that a Lovrak tablet is
      bioequivalent to a Zovirax tablet and that Lovrak suspension is bioequivalent to
      Zovirax suspension.

PMID- 15578769
TI  - Comparative bioavailability of two brands of atenolol 100 mg tablets (Tensotin
      and Tenormin) in healthy human volunteers.
AB  - A bioequivalence study of two oral formulations of 100 mg atenolol was carried
      out in 24 healthy volunteers following a single dose, two-sequence, cross-over
      randomized design at the International Pharmaceutical Research Centre (IPRC), as
      a joint venture with Al-Mowasah Hospital, Amman, Jordan. The two formulations
      were Tensotin (Julphar, UAE) as test and Tenormin (Zeneca, UK) as reference
      product. Both test and reference tablets were administered with 240 ml of water
      to each subject after an overnight fast on 2 treatment days separated by a 1 week
      washout period. After dosing, serial blood samples were collected for a period of
      36 h. Whole blood was analysed for atenolol by a sensitive, reproducible and
      accurate HPLC method with fluorescence detection capable of detecting atenolol in
      the range of 20-1600 ng/ml with a limit of quantitation of 20 ng/ml. Various
      pharmacokinetic parameters including AUC0-t, AUC0-proportional to), Cmax, Tmax,
      T1/2 and lambdaZ were determined from blood concentrations of both formulations
      and found to be in good agreement with reported values. AUC0-t, AUC0-proportional
      to), and Cmax were tested for bioequivalence after log-transformation of data
      using ANOVA and 90% confidence interval and were found within the acceptable
      range of 80%-125%. Based on these statistical inferences, it was concluded that
      Tensotin is bioequivalent to Tenormin.

PMID- 15578770
TI  - Stereospecific, enantioselective allylation of alpha-hydrazono esters by using
      allyltrichlorosilanes with BINAP dioxides as neutral-coordinate organocatalysts.

PMID- 15578771
TI  - A stereodivergent synthesis of virantmycin by an enzyme-mediated diester
      desymmetrization and a highly hindered aryl amination.

PMID- 15578772
TI  - Targeting RNAs with tobramycin analogues.

PMID- 15578773
TI  - Synthesis of the C-1027 chromophore framework through atropselective
      macrolactonization.

PMID- 15578774
TI  - A formal total synthesis of (+)-pinnatoxin A.

PMID- 15578775
TI  - Enantioselective synthesis of axially chiral phthalides through cationic
      [Rh(I)(H8-binap)]-catalyzed cross alkyne cyclotrimerization.

PMID- 15578776
TI  - Tungsten-lead triple bonds: syntheses, structures, and coordination chemistry of
      the plumbylidyne complexes trans-[X(PMe3)4W[triple bond]Pb(2,6-Trip2C6H3)].

PMID- 15578777
TI  - A Lewis acid catalyzed intramolecular [4+3] cycloaddition route to polycyclic
      systems that contain a seven-membered ring.

PMID- 15578778
TI  - Catalytic oxidation of CO with N2O on gas-phase platinum clusters.

PMID- 15578779
TI  - Alternating hetero H aggregation of different dyes by interstrand stacking from
      two DNA-dye conjugates.

PMID- 15578780
TI  - P. Yang receives Pure Chemistry Award.

PMID- 15578781
TI  - The molecular basis of olfactory chemoreception.

PMID- 15578782
TI  - A fatal affair: the ubiquitinylation of proteins.

PMID- 15578783
TI  - Argon and the non-inert pair: Rayleigh and Ramsay.

PMID- 15578784
TI  - Prolegomena to future experimental efforts on genetic code engineering by
      expanding its amino acid repertoire.
AB  - Protein synthesis and its relation to the genetic code was for a long time a
      central issue in biology. Rapid experimental progress throughout the past decade,
      crowned with the recently elucidated ribosomal structures, provided an almost
      complete description of this process. In addition important experiments provided
      solid evidence that the natural protein translation machinery can be reprogrammed
      to encode genetically a vast number of non-coded (i.e. noncanonical) amino acids.
      Indeed, in the set of 20 canonical amino acids as prescribed by the universal
      genetic code, many desirable functionalities, such as halogeno, keto, cyano,
      azido, nitroso, nitro, and silyl groups, as well as C=C or C[triple bond]C bonds,
      are absent. The ability to encode genetically such chemical diversity will enable
      us to reprogram living cells, such as bacteria, to express tailor-made proteins
      exhibiting functional diversity. Accordingly, genetic code engineering has
      developed into an exciting emerging research field at the interface of biology,
      chemistry, and physics.

PMID- 15578785
TI  - Reversible switching of DNA-gold nanoparticle aggregation.

PMID- 15578786
TI  - Supramolecular AB diblock copolymers.

PMID- 15578787
TI  - Four-stage amphoteric redox properties and biradicaloid character of tetra-tert
      butyldicyclopenta[b;d]thieno[1,2,3-cd;5,6,7-c'd']diphenalene.

PMID- 15578788
TI  - Is mayenite without clathrated oxygen an inorganic electride?

PMID- 15578789
TI  - Zn2[(S)-O3PCH2NHC4H7CO2]2: a homochiral 3D zinc phosphonate with helical
      channels.

PMID- 15578795
TI  - Caregiver burden not 'worse' after new public long-term care (LTC) insurance
      scheme took over in Japan.

PMID- 15578796
TI  - Early detection of Alzheimer's disease (AD) using the CANTAB paired Associates
      Learning Test.

PMID- 15578797
TI  - Structure of the 2003 impact factor for Croatian medical journal.
AB  - According to the Journal Citation Report from the Institute for Scientific
      Information (ISI), the last year's (2003) impact factor (IF) of the Croatian
      Medical Journal (CMJ) was 0.943. To determine the factors that contributed to
      this significant increase in the IF, we analyzed the structure of citations to
      CMJ in the ISI's publications, Science Citation Index (SCI), and Social Science
      Citation Index (SSCI). Thematic issues generally acquired more citations than
      regular issues. Furthermore, citation number varied for different article types.
      The citations to the original scientific articles corresponded to the average
      number of citations for the current IF value, whereas reviews and especially case
      reports were cited less frequently, and negatively contributed to the IF of the
      journal. Only half of all articles published in two previous years were cited in
      2003. The majority of these articles were cited once or twice, whereas only 15
      articles received more than three citations. Journal self-citations are still an
      important contributor to the CMJ's IF (39.6%). Their proportion may decrease in
      time, by further improving the visibility of the journal, and thus acquiring
      greater number of independent citations. In future, we can expect year-to-year
      variations in the journals IF. This trend may be positive on a long-term basis,
      but expectation of a value significantly higher than 1 is unrealistic. CMJ is
      small general medical journal whose quality-oriented editorial policy may in the
      long-term result in the increase in the IF.

PMID- 15578798
TI  - Academic medicine in Russia.
AB  - Academic medicine, along with professionalism of the medical community in Russia
      underwent a remarkable evolution from the Revolution through the decline of the
      Soviet Union. The Soviet period brought about an enormous expansion of numbers of
      admissions to medical schools and a corresponding increase in the number of new
      physicians. Academic medical institutions were separated from institutions of
      higher learning in general and medical science was separated from the mainstream
      of science. Many of these features have been reversed in the past 14 years and re
      professionalization of medicine has resumed.

PMID- 15578799
TI  - Revitalization of academic medicine in Macedonia--an urgent need.
AB  - This paper presents the current status of the academic medicine of the Skopje
      University Faculty of Medicine and the necessity of the medical education reform,
      initiated in 2001 by the decision of the Ss. Cyril and Methodius University
      Rectorate Administration to introduce the credit system in the university
      education in the Republic of Macedonia. This essay describes and reviews the
      actual conditions and priority problems and needs; proposes activities that
      should be undertaken to solve and overcome the existing problems and provide
      further development of teaching and research at the Faculty. Structural
      reorganization and overall mobilization of the human resources of the Faculty
      towards achieving the desired goals is needed.

PMID- 15578800
TI  - "Complementary and alternative" medicine--a measure of crisis in academic
      medicine.
AB  - Academic medicine integrates three of the most honorable human activities:
      treating the ill, teaching, and research. The quality that all three share is
      persistent quest for truth. However, there is reluctance of academic medicine
      today to openly defend scientific truth by challenging the arguments and the very
      existence of "complementary and alternative medicine" (CAM). There is no sound
      proof of CAM effectiveness, no hypotheses on the mechanisms of their action, nor
      scientific reports testing them. The fact that patients are charged for these
      "healing" activities makes CAM a plain fraud. With these facts in mind, the name
      "complementary and alternative medicine" is undeserved and misleading. CAM
      advocates maintain that CAM should be recognized precisely because it is widely
      practiced and very promising, that it has a special holistic/human approach, and
      works at least as a placebo in situations where medicine can do nothing more. As
      it seems that the public interest in paramedicine will only grow stronger before
      it grows weaker, scientists must raise their voice and question the truthfulness
      of CAM more openly. N of 1 randomized controlled trials (RCTs) should be used to
      test effectiveness of CAM, just as they are used to test any other treatment.
      Irrespectively of the noble principles of human rights and political correctness,
      academic medicine must discuss paramedicine equally openly and on the basis of
      the same criteria as it discusses its own activities, results, and plans.

PMID- 15578801
TI  - Evolution of hematopoietic stem cell transplantation in Eastern and Western
      Europe from 1990 to 2003. A report from the EBMT activity survey.
AB  - Transplantation of hematopoietic stem cells (HSCT) has seen rapid expansion
      during the last decade. It is evident that there are differences between eastern
      and western European countries when this high cost procedure is concerned. In
      order to obtain more insight into the mechanisms associated with these
      differences, we compared the transplant rates (number of transplants per 10
      million population) for allogeneic and autologous HSCT between selected eastern
      and western European countries and looked for factors associated with their
      differences. Data were obtained by the annual European Group for Blood and Marrow
      Transplantation (EBMT) activity survey for the period from 1990 to 2003.
      Transplant rates were substantially lower in eastern European countries for
      autologous, allogeneic, and unrelated HSCT throughout the observation period. The
      rapid increase in transplant rates during the 1990s occurred later in eastern
      European countries. Transplant rates continued to rise during the last three
      years in eastern European countries in contrast to a plateau in transplant rates
      in western European countries. There was a clear correlation between economic
      factors, measured as gross national income per capita, and transplant rates for
      low-income countries. There was also a clear correlation between team density
      (number of teams per 10 million population) and transplant rates. These data
      document that economic factors explain the differences in transplant rates
      between eastern and western European countries only in part. Another important
      factor seems to be the access to the therapeutic procedure. These data provide a
      basis for health care planning.

PMID- 15578802
TI  - Cardiovascular effects of thyroxine in combination with methimazole in
      premenopausal female Graves' disease patients: case-control study.
AB  - AIM: To evaluate cardiovascular consequences of combined treatment in Graves'
      disease patients with addition of thyroxine (LT4) to antithyroid drugs in doses
      sufficient to suppress serum thyrotropin (TSH) levels below normal. METHODS:
      Eleven premenopausal female patients who reached subnormal TSH levels (<0.3
      microIU/mL) under the combined therapy were evaluated by equilibrium radionuclide
      ventriculography at rest, and during the peak stage of fixed moderate exercise
      workload (75W) initially at diagnosis and after at least 8 months of stable
      euthyroidism, as judged by peripheral free thyroxine and triiodothyronine. The
      control group included 12 euthyroid healthy women. RESULTS: Post-treatment
      resting systolic and diastolic blood pressure, heart rate, and left ventricular
      (LV) systolic function were similar to control values. Log-transformed TSH
      releasing factor-stimulated TSH response correlated with LV resting early
      diastolic peak filling rate (PFR) (r=0.802, p=0.003) and resting diastolic blood
      pressure (r=0.795, p=0.003), which, in turn, was a significant predictor of basal
      renin secretion (r=-0.84, p=0.001). Treated patients had increased peak exercise
      systolic blood pressure (median 175, interquartile range 25 vs median 156,
      interquartile range 29 mmHg, p=0.019), delayed recovery of post-exercise heart
      rate to basal levels, and reduced exercise ejection fraction (median 66,
      interquartile range 9 vs median 74, interquartile range 13 %, p=0.037) in
      comparison with controls. Exercise ejection fraction was inversely related to
      exercise diastolic blood pressure, (r=-0.818, p=0.002); and exercise systolic
      blood pressure to exercise time to peak filling rate in a heart rate-independent
      manner, (rpartial=0.89, p<0.001). CONCLUSION: Persistent TSH suppression in LT4
      treated Graves' disease patients promotes pressure dependent renin secretion, and
      modulates resting early LV diastolic relaxation. It is also associated with
      exaggerated exercise systolic blood pressure response and decreased ejection
      fraction response to exercise.

PMID- 15578803
TI  - Prognostic significance of CD44 molecule in renal cell carcinoma.
AB  - AIM: To analyze the expression and the prognostic value of CD44s and variant v5
      and v6 isoforms in a large series of conventional renal cell carcinomas. METHODS:
      The expression of CD44 isoforms was immunohistochemically evaluated in 173
      conventional renal cell carcinomas, and was compared with the usual
      clinicopathological parameters such as tumor size, histological grade,
      pathological stage, and Ki-67 proliferative index. The relationship of the CD44
      expression to the cancer-specific survival was evaluated by log rank test.
      RESULTS: While normal renal tissue was negative for CD44s protein, it was
      upregulated in 70 (40.5%) out of 173 carcinomas, and its expression significantly
      correlated with histological grade (p<0.001), pathological stage (p=0.023), and
      Ki-67 proliferative index (p<0.001). Moreover, the expression of CD44s protein
      was an adverse prognostic parameter in univariate survival analysis for patients
      with tumors expressing high levels of CD44s protein (p=0.003). CD44v5 and v6
      isoforms were expressed in 11 (6.4%) and 28 (16.2%) tumors, respectively. Their
      expression was significantly higher in tumors with higher histological grade
      (p=0.001 and p=0.001, respectively). Also, the expression of v6 isoform was
      higher in tumors with high proliferation activity (p=0.001). CONCLUSION: CD44s
      molecule may play a role in the progression of conventional renal cell carcinoma,
      and may be used in the evaluation of disease outcome.

PMID- 15578804
TI  - Risk of acute bronchospasm and bronchial hyperreactivity from inhaled acid
      aerosol in healthy subjects: randomized, double-blind controlled trial.
AB  - AIM: To determine the risk of developing acute bronchial spasm and bronchial
      hyperreactivity in healthy subjects after inhaling hydrochloric acid aerosol of
      different pH, since various characteristics of inhaled aerosol, particularly its
      acidity, contribute to the reduction in lung function in patients with a pre
      existing disease. METHODS: Randomized, double-blind, placebo-controlled trial
      included 79 healthy volunteers. After submitting a written consent, they were
      randomized in 4 groups with approximately equal number of participants. Each
      group was exposed to acid aerosol of different pH. The respiratory lung function
      expressed by forced expiratory volume (FEV1), forced expiratory flow at 50%
      (FEF50), 75% (FEF25), and between 25% and 75% of vital capacity (FEF25/75), and
      non-specific bronchial reactivity were measured after inhalation of hydrochloric
      acid aerosol of pH 7.0, pH 5.0, pH 3.0, and pH 2.0 and compared with baseline
      values. Twelve subjects, who reached the threshold doses in both bronchial
      challenges, were tested again after receiving a systemic beta-blockade with a
      single oral dose of propranolol. RESULTS: Significant bronchospasm developed
      after the inhalation of hydrochloric acid aerosol of pH 5.0, 3.0, and 2.0. After
      the inhalation of aerosols of pH 5.0 and pH 2.0, all parameters of respiratory
      lung function (FEV1, FEF50, FEF25, and FEF25/75) significantly decreased. After
      the inhalation of aerosol of pH 3.0, all parameters significantly decreased
      except for FEF25, which showed no significant difference (1.84+/-0.46 before vs
      1.58+/-0.49 after inhalation; p=0.07). The inhalation of hydrochloric acid
      aerosol had no significant effect on the level of non-specific bronchial
      reactivity irrespective of its pH. Eight out of 12 subjects tested again after
      pretreatment with propranolol and with no significant change in the heart rate
      showed no change in non-specific bronchial reactivity in comparison with the 4
      subjects who reacted with a significant decrease in the heart rate (>10%), as
      well as in non-specific bronchial reactivity (p=0.023). CONCLUSION: Inhalation of
      acid aerosol in healthy subjects induced a bronchial spasm, but had no effect on
      non-specific bronchial reactivity except in subjects under systemic adrenergic
      inhibition.

PMID- 15578805
TI  - Sequential organ failure assessment score as the determinant of outcome for
      patients with severe sepsis.
AB  - AIM: To evaluate the impact of organ dysfunction in severe sepsis and determine
      the effectiveness of organ dysfunction scores to discriminate outcome after
      admission to the intensive care unit (ICU). METHODS: Patients with a diagnosis of
      severe sepsis and at least one organ dysfunction on the first day in the ICU
      (n=117) were included in the prospective observational study. The presence of
      organ dysfunction was assessed using a Sequential Organ Failure Assessment
      (SOFA). The severity of illness was assessed using a Simplified Acute Physiology
      Score (SAPS) II during the first 24 hours after the admission to the ICU. The
      main outcome was survival status on day 28 after admission to the ICU. RESULTS:
      Most common sites of infection were intra-abdominal and respiratory system (77
      and 38 cases, respectively). Median SAPS II score on admission was 47 points
      (25th-75th quartiles range, 37-57 points). Twenty eight days survival rate was
      41%. The best discrimination results were shown for cumulative scores with the
      highest for the SOFA score on day 3 in the ICU. The ability to discriminate
      outcome on day 1 was weak for the presence of dysfunction in all organ systems
      except neurological. The discriminative power of organ dysfunction scores
      increased during the stay in the ICU. Neurological and cardiovascular
      dysfunctions were the independent risk factors for mortality. CONCLUSION: The
      SOFA scores showed high accuracy in describing the course of organ dysfunction
      for the patients with severe sepsis. Evolving organ dysfunction following
      admission to the ICU strongly affected the outcome. Cumulative SOFA scores were
      better in discriminating outcome compared to single organ dysfunction scores.

PMID- 15578806
TI  - Prevalence of asthma and allergic diseases in Croatian children is increasing:
      survey study.
AB  - AIM: To estimate the prevalence of asthma, allergic rhinitis, and atopic
      dermatitis among school children in the region of Primorsko-goranska County in
      Croatia, and compare the results with data from other countries. METHODS: The
      study was conducted during the 2001-2002 school year, in complete adherence to
      the Phase One protocol of the International Study of Asthma and Allergies in
      Childhood (ISAAC). The target population comprised two age groups (6-7 and 13-14
      years) in the region of Primorsko-Goranska County in Croatia. Data were collected
      using standardized ISAAC written questionnaire and asthma video questionnaire.
      RESULTS: There were 1,634 participating children in the 6-7 age group (response
      rate 80.3%) and 2,194 participating children in the 13-14 age group (response
      rate 89.8%). Estimated 12-month prevalence rates of symptoms were: wheezing 9.7%
      and 8.4%, allergic rhinitis symptoms 16.9% and 17.5%, allergic
      rhinoconjunctivitis symptoms 5.6% and 6.7%, and atopic dermatitis symptoms 5.4%
      and 3.4%, for younger and older age group, respectively. CONCLUSION: Results
      suggest an increase in the prevalence of atopic disease symptoms in north-west
      part of Croatia over the last few decades when compared to prior studies. The
      results are suitable for international comparison, suggesting that this part of
      Croatia is a county with a moderate prevalence of atopic diseases in the
      pediatric population. The results represent a baseline for further
      epidemiological research of asthma and allergic diseases.

PMID- 15578807
TI  - Osteoarticular involvement in brucellosis: study of 196 cases in the Republic of
      Macedonia.
AB  - AIM: To describe the frequency, types, clinical characteristics, diagnostic
      tools, and outcome of osteoarticular brucellosis. METHODS: The study was carried
      out at the Hospital for Infectious Diseases in Skopje between January 1998 and
      December 2002. Three hundred and thirty one consecutive patients with brucellosis
      were enrolled and prospectively assessed according to a previously designed
      protocol. Brucellosis was diagnosed on the basis of clinical signs, and confirmed
      by the detection of specific antibodies at significant titers. RESULTS: One
      hundred and ninety six (59.2%) patients had osteoarticular involvement.
      Peripheral arthritis was found in 119 (60.7%) patients, followed by sacroiliitis
      in 60 (30.6%) and spondylitis in 56 (28.6%) of them. In 86 (43.9%) patients,
      osteoarticular changes were localized in two or more sites. The patients with
      osteoarticular brucellosis showed more prolonged illness prior to diagnosis and
      higher erythrocyte sedimentation rate, compared to those without osteoarticular
      localization. There were no other significant demographic, epidemiological,
      clinical, and laboratory differences between the two groups. Relapses occurred in
      28 (17.5%) and therapeutic failure in 25 (12.8%) patients, 24 of them with
      spondylitis. CONCLUSIONS: Osteoarticular brucellosis was a common form of focal
      brucellosis and the most unfavorable outcome was seen in patients with
      spondylitis.

PMID- 15578808
TI  - Importance of intervertebral disc size in low back pain.
AB  - AIM: To compare two anthropometrical methods for measuring the intervertebral
      disc size with computer tomography measurements and to develop a new
      anthropometric method for calculating intervertebral disc area. METHODS:
      Intervertebral disc size was measured using computer tomography and two
      anthropometric methods (Colombini and modified Colombini) in a sample of 40
      subjects. The new calculation for intervertebral disc size was developed and used
      in a sample of male bus drivers with (n=65) and without (n=30) anamnestic low
      back pain to asses clinical usefulness. RESULTS: The modified anthropometric
      method for intervertebral disc size assessment correctly predicted intervertebral
      disc size in 89% of the cases and the determination error was diminished to an
      average of 4.1% for level L4-L5 and 4.4% for level L5-S1. The average size of the
      intervertebral discs in 65 subjects with anamnestic lower back problems was
      significantly smaller than in the control group of 30 subjects having no such
      problems (p<0.001). CONCLUSION: The use of the presented formulas for the
      calculation of the intervertebral disc in L4-5 and L5-S1 areas from the data
      obtained by simple anthropometrical measurements is sufficiently reliable and
      accurate. The method is economical and harmless.

PMID- 15578809
TI  - Osteosarcoma and Ewing's sarcoma in children and adolescents: retrospective
      clinicopathological study.
AB  - AIM: Almost 20 different prognostic factors have so far been investigated in
      childhood bone tumors, but apart from clinical stage the results have been
      inconclusive. We evaluated possible prognostic factors of malignant bone tumors
      in children and adolescents. METHODS: Seventy children and adolescents, who have
      been treated for bone sarcomas (36 with osteosarcoma and 34 with Ewing's sarcoma)
      at the Children's Hospital in Zagreb and the Orthopedic Clinic of the Zagreb
      University School of Medicine were included in the study. We analyzed 9
      variables: clinical stage, patient age and sex, tumor size and location, location
      of metastases, chemotherapy response, concentration of lactate dehydrogenase
      (LDH) and erythrocyte sedimentation rate (ESR), and chondroid differentiation in
      osteosarcoma. RESULTS: The clinical stage was the most important prognostic
      factor for both type of tumors. Lactate dehydrogenase in patients with Ewing's
      sarcoma (p=0.033) and in patients with osteosarcoma (p=0.015) as well as
      erythrocyte sedimentation rate (p<0.001 and p=0.014, respectively) may also be of
      predictive value. CONCLUSION: Elevated erythrocyte sedimentation rate and high
      LDH concentration seem to be of importance in both Ewing's sarcoma and
      osteosarcoma, regardless of their different pathogenesis or pathohistology.

PMID- 15578810
TI  - Plasma concentration of immunoglobulin classes and subclasses in children with
      autism in the Republic of Macedonia: retrospective study.
AB  - AIM: To examine plasma concentration of IgA, IgM, IgG classes, and IgG1, IgG2,
      IgG3, and IgG4 subclasses in children with autism. METHODS: Infantile autism was
      diagnosed by the Diagnostic and Statistical Manual for Mental Disorders (DSM)-IV
      and the International Classification of Diseases (ICD)-10 criteria. Plasma
      samples were collected from 35 autistic subjects, and their 21 siblings
      (biological brothers and sisters) who served as healthy controls. Plasma samples
      were separated by centrifugation and stored at -20 degrees C until the
      determination. Plasma immunoglobulin classes (IgM, IgA, IgG) and subclasses
      (IgG1, IgG2, IgG3, IgG4) were determined using a nephelometer. RESULTS: Plasma
      concentrations (mean+/-standard deviation) of IgM and IgG in autistic children
      (1.36+/-0.31 g/L and 13.14+/-1.27 g/L, respectively) were significantly higher
      (p=0.031 and p=0.023, respectively) in comparison with their healthy brothers or
      sisters (1.20+/-0.15 g/L and 12.39+/-0.96 g/L, respectively). Children with
      autism had significantly higher plasma concentrations of IgG4 (p<0.001) compared
      to their siblings (healthy brothers or sisters). Plasma concentration of IgA,
      IgG1, IgG2, and IgG3 were similar in autistic children and their healthy brothers
      or sisters. Increased plasma concentration of IgG1 was found (p=0.027) in
      autistic males (8.06+/-2.40), as compared with their healthy brothers (5.24+/
      4.13 g/L). Plasma concentrations of IgG (14.28+/-3.66 g/L), and IgG1 (9.41+/-2.20
      g/L) in autistic females were increased (p=0.012 and p=0.021, respectively) in
      comparison with IgG (11.07+/-2.07) and IgG1 (6.37+/-3.38 g/L) in their healthy
      sisters. CONCLUSION: Children with autism have increased plasma concentration of
      immunoglobulines. Increased immunoglobulines in children with autism could be a
      result of impaired development of the immune system, and/or genetic factors
      connected with defense mechanism in these children.

PMID- 15578811
TI  - Survey of health status and quality of life of the elderly in Poland and Croatia.
AB  - AIM: To describe health status and the quality of life among the Polish and
      Croatian elderly and explore differences between the countries, as well as
      patterns of gender and age differences. METHODS: Randomly chosen elderly aged 65
      85 from Krakow (Poland) and from Zagreb and some smaller towns in Croatia were
      interviewed on health (self-rated health, physical functioning, mental health,
      perceived bodily pain, hearing and vision ability, morbidity, functional status,
      loneliness and depression) and general quality of life. The database (528 and 286
      interviews with the Polish and Croatian elderly, respectively) was analyzed using
      the Mann-Whitney U test, Kruskal-Wallis H test, and general linear model
      procedure. RESULTS: Significant differences in favor of the Croatian elderly were
      found in self-rated health and perceived bodily pain (controlled for age, gender,
      education, and morbidity). The Polish elderly experienced fewer depressive
      symptoms and reported better vision ability and quality of life in comparison
      with the Croatian elderly. With some exceptions (hearing and vision ability) the
      collected data confirmed better health status and quality of life in men in
      comparison with women in both countries. Significant trends were found in
      deterioration of health with age. However, the pattern of deteriorating health
      with age was inconsistent, and more visible among women than among men. Health
      status results in Poland and Croatia were generally lower in comparison with
      elderly populations in Western Europe. CONCLUSION: The findings suggest that the
      broadest possible panel of instruments should be used to describe health within
      each country and to compare health between the countries. Poor health and quality
      of life produce a considerable task for public health bodies in Poland and
      Croatia to equal the standards of the European Union.

PMID- 15578812
TI  - Social variations in infant growth performance in Severodvinsk, Northwest Russia:
      community-based cohort study.
AB  - AIM: To examine infant growth characteristics and their socio-demographic
      determinants in Severodvinsk, northwest Russia. METHODS: Length-for-age, weight
      for-age, and weight-for-length Z-scores of 1,067 infants born in 1999-2000 in
      Severodvinsk were calculated on the basis of the data on the length and weight
      obtained from the medical files. Multiple linear regression was used to estimate
      independent effects of maternal age, education, occupation, marital status,
      weight, parity, sex of the baby, and breastfeeding duration on infant growth.
      RESULTS: At the age of 12 months, 1.1% of the infants were stunted, 1.1%
      underweight, and 0.5% wasted in comparison with the Centers for Disease Control
      and Prevention 2000 reference population. The mean Z-scores for length-for-age,
      weight-for-age, and weight-for-length were 0.48+/-0.93, 0.38+/-1.04, and 0.65+/
      1.03, respectively. Mean weight-for-length Z-scores considerably increased from
      birth to 12 months, while length-for-age Z-score remained largely unchanged. In
      regression analysis, length-for-age Z-scores were lower by 0.43 (p=0.028) and by
      0.30 (p<0.001) in infants born to mothers with basic and unknown education,
      respectively. Positive trends between linear growth and maternal age (p=0.027)
      and education (p=0.024) were observed. No social variations in weight-for-length
      Z-scores were found. CONCLUSION: Prevalence of stunting, underweight, and wasting
      were lower than previously reported from Russia, which may reflect good overall
      socio-economic conditions in the town. Social variations in linear growth
      indicate the existence of inequalities in infant health, which may further
      increase with age.

PMID- 15578813
TI  - Alcohol consumption and mortality in Serbia: twenty-year follow-up study.
AB  - AIM: To investigate the connection between alcohol consumption and general and
      specific mortality in the Serbian population. METHODS: Total of 286 healthy
      middle-aged participants of both genders enrolled in a prospective follow-up
      study in 1974. During the following 20 years, 80 deaths occurred. The data on
      underlying causes of death were obtained from official death certificates.
      Alcohol consumption was estimated from a multiple-choice questionnaire. According
      to the total daily alcohol intake, subjects were classified into 3 groups: none-
      or rare drinkers, moderate, and heavy drinkers. The relative risks (RR) adjusted
      for gender, smoking, body mass index, and blood pressure were calculated using
      non-drinkers as a reference category. RESULTS: Heavy drinkers exhibited
      significantly higher adjusted ratios for all-cause mortality (RR=1.970, 95%
      confidence interval [CI]=1.062-3.651; p=0.031) and myocardial infarction
      (RR=2.463, 95% CI=1.050-5.775; p=0.038), and non-significantly higher risk for
      death from other causes. Moderate drinkers exhibited lower adjusted risk ratios
      for all-cause mortality, myocardial infarction and death from other causes, but
      this decrease did not reach the significance level. Further, overall probability
      of survival at every time point was the highest among moderate drinkers and
      lowest among heavy drinkers. CONCLUSION: Among Serbian middle-aged population
      moderate alcohol consumption reduced mortality from all causes, myocardial
      infarction and other causes of death, and increased the probability of survival
      in a twenty year follow-up period. Heavy drinking increased mortality rates from
      all causes and reduced the twenty year-survival probability in comparison with
      non-drinkers.

PMID- 15578814
TI  - Peripheral nerve conduction study in workers exposed to a mixture of organic
      solvents in paint and lacquer industry.
AB  - AIM: To compare levels of combined exposure to white spirit, toluene, butyl
      acetate, ethyl acetate, and xylene in the manufacturing of paint, cartridge,
      drying, and top-coat sections of paint and lacquer industry, and peripheral nerve
      conduction parameters in the exposed workers. METHODS: The exposed group
      comprised 120 workers while the control group included 110 workers who had never
      been exposed to the above listed organic solvents. Nerve conduction studies of
      the radial and tibial anterior nerve were performed in both groups. RESULTS:
      Motor and sensitive conduction velocity, as well as terminal latency of the
      radial and tibial anterior nerve showed significant changes in exposed workers in
      comparison to those of the control group (p<0.001). These parameters were
      significantly changed in workers with long length exposure to the toxic agents.
      In early stages of exposure, neural conduction parameters of the radial nerve
      were the most sensitive parameters in detecting subclinical peripheral nerve
      changes (p<0.001). There was significant correlation between the nerve conduction
      changes and urinary levels of hippuric and methyl-hippuric acids (p<0.01).
      CONCLUSION: The results of the study suggest neurotoxic effects of the mixture of
      white spirit, toluene, butyl acetate, ethyl acetate, and xylene detected in paint
      and lacquer industry. Standard measurement of the urinary levels of hippuric and
      methyl-hippuric acids could be a useful indicator of need for nerve conduction
      studies and the subclinical peripheral neuropathy screening in exposed workers.

PMID- 15578815
TI  - Coffee and alcohol consumption as triggering factors for sudden cardiac death:
      case-crossover study.
AB  - AIM: To estimate the relative risk of triggering sudden cardiac death after
      coffee or alcohol consumption in out-of-hospital sudden cardiac death victims.
      METHODS: A case-crossover design with usual frequency approach was used and the
      study population included persons who died out of hospital due to sudden cardiac
      death. By mailing 2 questionnaires, 1 to the family members of the deceased and
      the other to the attending physician, necessary data on the mode of cardiac
      death, life style, health, and several socio-demographic variables were obtained.
      Cases were those who died of sudden cardiac death within 1 hour after coffee
      consumption or within 2 hours after ingesting alcohol; but controls were those
      who died in the hours when they were not exposed to these stimulans. The relative
      risk of dying within exposed hours in comparison to non-exposed hours was
      parameter estimated for each risk factor. RESULTS: Among 309 sudden cardiac death
      victims who died in the period from January 2000 to March 2001 in Slovenia, there
      were 253 men and 56 women with median age at death of 57.1 and 57.7,
      respectively. On average, each of them had 2.8 risk factors for ischemic heart
      disease, and the estimated relative risk of dying during 1 hour after coffee
      consumption was 1.73 (95% confidence interval [CI]=1.13-2.65), and within 2 hours
      after alcohol consumption 3.00 (95%CI=1.61-5.68). Within both coffee drinking and
      alcohol consuming groups, the relative risk was different among persons with
      different life style habits. It ranged from 1.50 for the coffee drinkers who had
      been receiving medication due to risk factors of heart diseases, to 2.63 for
      former alcohol drinkers. Among alcohol consumers it varied from 2.66 among those
      who were performing less than 104 hours of physical activity of six metabolic
      equivalents at least, to 52.15 among those of 90 heart beats or more per minute.
      CONCLUSION: Our research confirmed the hypothesis that coffee or alcohol
      consumption is a potential trigger for sudden cardiac death in persons with risk
      factors for ischemic heart disease.

PMID- 15578816
TI  - Technological development will help people get better health care: true or false?

PMID- 15578817
TI  - Can medicine contribute to preventing war?

PMID- 15578818
TI  - Quality of patient care in bone marrow transplantation.

PMID- 15578819
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 15578820
TI  - European neurosurgical societies.

PMID- 15578822
TI  - Metalloprotein folding.

PMID- 15578823
TI  - Site selection in tandem arrays of metal-binding domains.
AB  - The metal binding properties of peptides corresponding to metal-binding sites
      spanning regions that normally function as linkers in tandem arrays of metal
      binding domain-containing proteins were examined. For a peptide with two His
      residues from one TFIIIA-like zinc finger domain, a canonical TFIIIA-like linker,
      and two Cys residues from an adjacent zinc domain, the dissociation constant for
      the 1:1 peptide to cobalt(II) was found to be 15 +/- 10 microM, compared with 60
      nM for the corresponding zinc finger domains themselves. Peptides overlapping two
      sets of metal-binding domains from human TRAF (tumor necrosis factor receptor
      associated factor) proteins were examined. In one case, the affinity of the
      presumed metal-binding domain and that for the linker region were comparable,
      while in the second case, the affinity of the linker peptide was higher than that
      for the corresponding presumed metal-binding domain peptide. These studies
      revealed that cobalt(II) affinities in the micromolar range can occur even for
      peptides that do not correspond to natural zinc-binding domains and that the
      degree of distinction between authentic metal-binding domains and the
      corresponding linker-spanning peptides may be modest, at least for single domain
      peptide models.

PMID- 15578824
TI  - Understanding metalloprotein folding using a de novo design strategy.
AB  - Metal ions play significant roles in most biological systems. Over the past two
      decades, there has been significant interest in the redesign of existing metal
      binding sites in proteins/peptides and the introduction of metals into folded
      proteins/peptides. Recent research has focused on the effects of metal binding on
      the overall secondary and tertiary conformations of unstructured
      peptides/proteins. In this context, de novo design of metallopeptides has become
      a valuable approach for studying the consequence of metal binding. It has been
      seen that metal ions not only direct folding of partially folded peptides but
      have at times also been the elixir for properly folding random-coil-like
      structures in stable secondary conformations. Work in our group has focused on
      binding of heavy metal ions such as Hg(II) to de novo designed alpha-helical
      three stranded coiled coil peptides with sequences based on the heptad repeat
      motif. Removal from or addition of a heptad to the parent 30-residue TRI peptide
      with the amino acid sequence Ac-G(LKALEEK)(4)G-NH(2) generated peptides whose
      self-aggregation affinities were seen to be dependent on their lengths. It was
      noted that adjustment in the position of the thiol from an "a" position in the
      case of the shorter BabyL9C to a "d" position for BabyL12C resulted in a peptide
      with low association affinities for itself, weaker binding with Hg(II), and a
      considerably faster kinetic profile for metal insertion. Similar differences in
      thermodynamic and kinetic parameters were also noted for the longer TRI peptides.
      At the same time, metal insertion into the prefolded and longer TRI and Grand
      peptides has clearly demonstrated that the metal binding is both
      thermodynamically as well kinetically different from that to unassociated
      peptides.

PMID- 15578825
TI  - Design, folding, and activities of metal-assembled coiled coil proteins.
AB  - Metal ions serve many purposes in natural proteins, from the stabilization of
      tertiary structure to the direction of protein folding to crucial roles in
      electron transfer and catalysis. There is considerable interest in creating metal
      binding sites in designed proteins to understand the structural role of metal
      ions and to design new metalloproteins with useful functions. The de novo design
      of metalloproteins and the role of metals in the folding of designed proteins are
      reviewed here, with particular focus on the design, folding, and activities of
      the [M(bpy-peptide)(3)](2+) structure. This maquette is constructed by the
      covalent attachment of 2,2'-bipyridine to the N-termini of amphiphilic peptides,
      and it is assembled into a folded trimeric coiled coil by the addition of a six
      coordinate transition metal ion and the resulting hydrophobic collapse of the
      peptides. The [M(bpy-peptide)(3)](2+) structure has been employed in diverse
      applications, ranging from electron transfer pathway studies to the study of
      optimal hydrophobic packing in a virtual library to the construction of receptors
      and biosensors.

PMID- 15578826
TI  - Role of cofactors in folding of the blue-copper protein azurin.
AB  - Many proteins in living cells coordinate cofactors, such as metal ions, to attain
      their activity. Since the cofactors in such cases often can interact with their
      corresponding unfolded polypeptides in vitro, it is important to unravel how
      cofactors modulate protein folding. In this review, I will discuss the role of
      cofactors in folding of the blue-copper protein Pseudomonas aeruginosa azurin. In
      the case of both copper (Cu(II) and Cu(I)) and zinc (Zn(II)), the metal can bind
      to unfolded azurin. The residues involved in copper (Cu(II) and Cu(I))
      coordination in the unfolded state have been identified as Cys112, His117, and
      Met121. The affinities of Cu(II), Cu(I), and Zn(II) are all higher for the folded
      than for the unfolded azurin polypeptide, resulting in metal stabilization of the
      native state as compared to the stability of apo-azurin. Cu(II), Zn(II), and
      several apo forms of azurin all fold in two-state kinetic reactions with roughly
      identical polypeptide-folding speeds. This suggests that the native-state beta
      barrel topology, not cofactor interactions or thermodynamic stability, determines
      azurin's folding barrier. Nonetheless, copper binds much more rapidly (i.e., 4
      orders of magnitude) to unfolded azurin than to folded azurin. Therefore, the
      fastest route to functional azurin is through copper binding before polypeptide
      folding; this sequence of events may be the relevant biological pathway.

PMID- 15578827
TI  - Folding, conformational changes, and dynamics of cytochromes C probed by NMR
      spectroscopy.
AB  - NMR spectroscopy has become a vital tool for studies of protein conformational
      changes and dynamics. Oxidized Fe(III)cytochromes c are a particularly attractive
      target for NMR analysis because their paramagnetism (S = (1)/(2)) leads to high
      (1)H chemical shift dispersion, even for unfolded or otherwise disordered states.
      In addition, analysis of shifts induced by the hyperfine interaction reveals
      details of the structure of the heme and its ligands for native and nonnative
      protein conformational states. The use of NMR spectroscopy to investigate the
      folding and dynamics of paramagnetic cytochromes c is reviewed here. Studies of
      nonnative conformations formed by denaturation and by anomalous in vivo
      maturation (heme attachment) are facilitated by the paramagnetic, low-spin nature
      of native and nonnative forms of cytochromes c. Investigation of the dynamics of
      folded cytochromes c also are aided by their paramagnetism. As an example of this
      analysis, the expression in Escherichia coli of cytochrome c(552) from
      Nitrosomonas europaea is reported here, along with analysis of its unusual heme
      hyperfine shifts. The results are suggestive of heme axial methionine fluxion in
      N. europaea ferricytochrome c(552). The application of NMR spectroscopy to
      investigate paramagnetic cytochrome c folding and dynamics has advanced our
      understanding of the structure and dynamics of both native and nonnative states
      of heme proteins.

PMID- 15578828
TI  - Insights into partially folded or unfolded States of metalloproteins from nuclear
      magnetic resonance.
AB  - Nuclear magnetic resonance (NMR) provides detailed insights into the
      conformational features of unfolded and partially folded proteins. In the case of
      metalloproteins, special attention should be devoted to the characterization of
      the properties of the metal binding sites, and specific approaches need to be
      developed depending on the nature of the metal ion and its coordination
      environment. At the same time, metal-based NMR parameters may help in getting a
      better picture of the average structural properties of the metalloprotein. A
      critical evaluation of the limits of applicability of paramagnetic effects for
      solution structure determination in partially folded or unfolded proteins is
      presented. The coupling between NMR characterization of structure and dynamic of
      the polypeptide chain and of the metal environment provides insights into the
      stabilizing role of metal ions in metalloproteins. The overall approach is
      illustrated for some case examples of increasing flexibility obtained far from
      native conditions for cytochrome c and superoxide dismutase, two metalloproteins
      that have been extensively studied in our lab and whose misfolded forms may be
      relevant for important biological processes.

PMID- 15578829
TI  - Zinc-porphyrin Solvation in folded and unfolded states of Zn-cytochrome c.
AB  - After a brief review of the use of photochemical triggers and heme metal
      substitution to probe the folding dynamics of cytochrome c, we present new
      results on the photophysics and photochemistry of folded and unfolded states of
      the zinc-substituted protein (Zn-cyt c). Our measurements of Zn-cyt c triplet
      state decay kinetics reveal a systematic isotope effect on lifetimes: the decay
      in the folded protein (tau(H)2(O) approximately 10 ms) is only modestly affected
      by isotopically substituted buffers (k(H)2(O)/k(D)2(O) = 1.2), whereas a reduced
      triplet lifetime (approximately 1.3 ms) and greater isotope effect (1.4) were
      found for the chemically denatured, fully unfolded protein. The shortest lifetime
      (0.1-0.4 ms) and greatest isotope effect (1.5) were found for a fully exposed
      model compound, zinc-substituted N-acetyl-microperoxidase-8 (ZnAcMP8), implying
      that the unfolded protein provides some protection to the Zn-porphyrin group even
      under fully denaturing conditions. Further evidence for partial structure in
      unfolded Zn-cyt c comes from bimolecular quenching experiments using
      Ru(NH(3))(6)(3+) as an external Zn-porphyrin triplet state quencher. In the
      presence of quencher, partially unfolded protein at midpoint guanidinium chloride
      (GdmCl) and urea concentrations exhibits biphasic triplet decay kinetics, a fast
      component corresponding to an extended, solvent-exposed state (6.6 x 10(8) M(-1)
      s(-1) in GdmCl, 6.3 x 10(8) M(-1) s(-1) in urea) and a slow component
      attributable to a compact, relatively solvent-inaccessible, state (5.9 x 10(7) M(
      1) s(-1) in GdmCl, 8.6 x 10(6) M(-1) s(-1) in urea). The variation in Zn
      porphyrin solvation for the compact states in the two denaturants reveals that
      the cofactor in the partially unfolded protein is better protected in urea
      solutions.

PMID- 15578830
TI  - Synthesis and structure of the pentacopper(II) substituted tungstosilicate
      [Cu5(OH)4(H2O)2(A-alpha-SiW9O33)2]10-.
AB  - The dimeric, pentacopper(II) substituted tungstosilicate
      [Cu(5)(OH)(4)(H(2)O)(2)(A-alpha-SiW(9)O(33))(2)](10-) (1) has been synthesized in
      good yield using a one-pot procedure by reaction of Cu(2+) ions with the
      trilacunary precursor salt K(10)[A-alpha-SiW(9)O(34)]. The title polyanion
      represents the first polyoxotungstate substituted by 5 copper centers and the
      central copper-hydroxo-aqua fragment is completely unprecedented. In the course
      of the reaction, two [A-alpha-SiW(9)O(34)](10-) Keggin half-units have fused in
      an asymmetrical fashion resulting in the lacunary polyoxotungstate
      [Si(2)W(18)O(66)](16-). The vacancy in this species is stabilized by a magnetic
      cluster of five octahedrally coordinated Cu(2+) ions resulting in polyanion 1
      with C(2v) symmetry.

PMID- 15578831
TI  - [Co(en)3][Sb12S19]: a new antimony sulfide with a zeolite-like structure
      containing one-dimensional channels.
AB  - Solvothermal synthesis affords access to the first truly three-dimensional
      antimony-sulfide framework which contains one-dimensional circular channels.

PMID- 15578832
TI  - Synthesis and characterization of a novel tantalum chalcogen-rich molecular
      cluster with square planar metal core.
AB  - Black single crystals of Ta(4)Se(9)I(8) are obtained in a high yield by heating
      Ta, Se, and I(2) at 300 degrees C in 1:2.2:1.0 molar ratio. In the structure, the
      tantalum atoms form a square, with four Se(2) ligands bridging the Ta-Ta edges
      and one capping the square. Each Ta atom has two terminal iodine atoms. The
      compound is diamagnetic and has only two electrons for metal-metal bonding.

PMID- 15578833
TI  - Photodecarbonylation of ruthenium carbonyl octaethylporphyrin via stepwise two
      photon absorption of visible light.
AB  - The photoinduced decarbonylation of a ruthenium(II) carbonyl octaethylporphyrin
      (RuOEP(CO)(Py)) complex has been shown to occur upon nanosecond pulse laser
      irradiation as a visible light excitation source, which is reasonably interpreted
      by a stepwise two-photon absorption process.

PMID- 15578834
TI  - Energetic salts from N-aminoazoles.
AB  - New energetic salts (2, 3, 5, 6, 13, 14, 21, 22) were synthesized via the
      quaternization of derivatives of N-aminoazoles with nitric or perchloric acid or
      with iodomethane followed by metathesis reaction with silver nitrate or silver
      perchlorate. The structure of 2-amino-4,5-dimethyltetrazolium nitrate (21) was
      confirmed by single-crystal X-ray analysis. Most of the salts exhibit good
      thermal stabilities and low melting points. By using experimentally determined
      constant volume combustion energies, the standard molar enthalpies of formation
      were derived on the basis of designed Hess thermochemical cycles.

PMID- 15578835
TI  - Influence of the halogen ligand on the near-UV-visible spectrum of
      [Ru(X)(Me)(CO)2(alpha-diimine)] (X = Cl, I; alpha-diimine = Me-DAB, iPr-DAB; DAB
      = 1,4-diaza-1,3-butadiene): an ab initio and TD-DFT analysis.
AB  - The near-UV-vis electronic spectroscopy of [Ru(X)(Me)(CO)(2)(iPr-DAB)] (X = Cl or
      I; iPr-DAB = N,N'-di-isopropyl-1,4-diaza-1,3-butadiene) is investigated through
      CASSCF/CASPT2 and TD-DFT calculations on the model complexes [Ru(X)(Me)(CO)(2)(Me
      DAB)] (X = Cl or I). Convergence of the calculated transition energies for the
      low-lying metal-to-ligand charge-transfer (MLCT), X-to-ligand charge-transfer
      (XLCT, X halide ligand), or sigma-bond-to-ligand charge-transfer (SBLCT) to
      experimental values is analyzed for both methods. On the basis of these accurate
      calculations, it is shown that whereas the lowest singlet state can be assigned
      to a nearly pure XLCT state in [Ru(I)(Me)(CO)(2)(Me-DAB)], its character is
      mainly MLCT in [Ru(Cl)(Me)(CO)(2)(Me-DAB)]. These results are in agreement with
      time-resolved emission/IR and resonance Raman experimental data. The experimental
      UV-vis bands are well reproduced by the CASSCF/CASPT2 calculations. The TD-DFT
      transition energies to the long-range charge transfer states are dramatically
      affected by the nature of the functional, with lowering leading to meaningless
      values in the case of nonhybrid functionals. Both methods reproduce well the red
      shift of the absorption bands on going from the chloride to the iodide complex as
      well as the shift of the strongly absorbing higher MLCT transition from the
      visible to the UV domain of energy.

PMID- 15578836
TI  - Efficient DNA binding by optically Pure Ruthenium Tris(bipyridyl) complexes
      incorporating carboxylic functionalities. Solution and structural analysis.
AB  - Herein, we report on the binding of optically pure ruthenium complexes Delta- or
      Lambda-[Ru(bpy)(2)(L-L)][PF(6)](2) [L-L = Hcmbpy = 4-carboxy-4'-methyl-2,2'
      bipyridine (1), L-L = H(2)dcbpy = 4,4'-dicarboxy-2,2'-bipyridine (2)] to DNA. The
      binding constants of the two enantiomeric Delta-1 and Lambda-1 complexes to DNA
      were estimated from titration monitored by (1)H NMR spectroscopy. 2D transferred
      NOESY (TRNOESY) experiments support the conclusion that Delta-1 and Lambda-1 bind
      to DNA and that an intermediate-to-fast exchange occurs between bound and free
      Ru(II) complex. Further, evidence for enantioselective DNA cleavage by Delta-2 is
      provided by means of gel electrophoresis performed in the presence and in the
      absence of light; in contrast, the Lambda-2 enantiomer does not. The IR spectrum
      of enantiomer Delta-2 (or Lambda-2) compared to that of the racemate (rac-2)
      gives evidence that, in the latter form, the enantiomers are strongly associated.
      Moreover the X-ray structure of rac-2 was also determined and exhibits as an
      outstanding feature the formation of a one-dimensional supramolecular species in
      which the cohesion of the system is maintained by strong hydrogen bonding between
      carboxylic acid groups of enantiomers Delta-2 and Lambda-2 (cationic parts) with
      d(O...O) = 2.6 A in agreement with the infrared results. The conclusion that can
      be drawn from IR and X-ray spectroscopies together is that the self-association
      in rac-2 is strong.

PMID- 15578837
TI  - Chiral induction in self-assembled helicates: CHIRAGEN type ligands with
      ferrocene bridging units.
AB  - The aim of this work was the preparation of enantiomerically pure bis(pinene
      bipyridine) ligands containing the ferrocenyl moiety. Several such ligands (1-3)
      were synthesized and completely characterized. These molecules can be
      diastereoselectively deprotonated at the acidic methylene group of the pinene
      moiety using a strong and sterically hindered base such as LDA. Subsequent
      reaction of the formed anion with alkyl halides yield the family of C(2)
      symmetric enantiopure compounds (1a-c). Copper(I), silver(I), or zinc(II)
      complexes with several ligands (C1-C8) were prepared and structurally
      characterized in the solid state and in solution. Self-assembled helical species
      are formed in several cases. It became evident that the chiral groups present in
      the ligand do not completely determined the helical configuration of the
      assemblages. Diastereoselectivity is thus not complete with this type of ligands,
      contrary to other, similar ligands studied before.

PMID- 15578838
TI  - A novel chainlike As-V-O polymer based on a transition metal complex and a
      dimeric polyoxoanion.
AB  - The novel polyoxometalate
      ([As(8)V(13)NiClO(41)][Ni(en)(2)(H(2)O)][Ni(en)(2)])([Ni(en)(2)(H(2)O)(2)](0.5)).
      H(2)O (1), which is the first example of a chainlike inorganic-organic hybrid
      polymer based on dimeric polyoxoanions linked by nickel complex fragments, has
      been synthesized in the system of As(2)O(3)-V(2)O(5)-H(2)C(2)O(4)-en
      NiCl(2).6H(2)O-H(2)O under hydrothermal conditions and characterized by IR, TGA,
      elemental analysis, single crystal X-ray diffraction, XPS, and magnetic
      susceptibility studies, respectively. This compound crystallized in the triclinic
      space group P with a = 13.358(3) angstroms, b = 14.198(3) angstroms, c =
      19.723(4) angstroms, alpha = 83.88(3) degrees, beta = 86.04(3) degrees, gamma =
      64.66(3) degrees, V = 3360.2(2) angstroms(3), and Z = 2. Interestingly, the
      dimeric polyoxoanion contains two ([Ni(en)(2)(H(2)O)][As(8)V(13)NiClO(41)])
      cluster units linked by Ni-O-As bonds and is a Ni-substituted
      [As(8)V(13)NiClO(41)] cluster supported by [Ni(en)(2)(H(2)O)] coordination
      fragment. The chainlike structure consists of
      ([Ni(en)(2)(H(2)O)][As(8)V(13)NiClO(41)])(2) dimeric polyoxoanions and
      [Ni(en)(2)] groups which are linked together through vertexes forming a unique
      one-dimensional polymer. The study of the magnetic susceptibility of 1
      demonstrates the presence of antiferromagnetic interaction in 1.

PMID- 15578839
TI  - Anion ordering and defect structure in Ruddlesden-Popper strontium niobium
      oxynitrides.
AB  - The crystal structure of the n = 1 member of the Ruddlesden-Popper family
      (SrO)(SrNbO(2)N)(n) was refined by the Rietveld method using neutron powder
      diffraction data. This complex crystallizes in the I4/mmm space group with cell
      parameters a = 4.0506(2) and c = 12.5936(9) angstroms. The refined composition
      was Sr(2)NbO(3.28)N(0.72), which corresponds to a formal oxidation state for Nb
      of +4.72, meaning 72% Nb(V) and 28% Nb(IV). The nitrogen atoms order in the
      equatorial sites of the niobium octahedra according to Pauling's second crystal
      rule as the more charged anion occupies the site showing the larger bond strength
      sums. Pauling's second crystal rule is shown to be able to predict the
      distribution of anions in the available crystallographic sites in other mixed
      anion systems such as oxyhalides with K(2)NiF(4) structures and other
      oxynitrides. The defect structure of the n = 1 and n = 2 members of the same
      family was investigated by high-resolution electron microscopy. Recurrent
      intergrowth along the c axis with other Ruddlesden-Popper members (n = 3, 4, and
      perovskite) is observed, resulting in streaking along this direction in the
      corresponding electron diffraction patterns.

PMID- 15578840
TI  - Fluorescent coordination networks of 2,3,6,7,10,11
      hexakis(phenylthio)triphenylene and silver(I) triflate.
AB  - The polycyclic aromatic ligand 2,3,6,7,10,11-hexakis(phenylthio)triphenylene
      (HPhTT) coordinates with AgTf (Tf = trifluoromethylsulfonate) to form 1D networks
      with various solvent molecules included. In particular, the crystal structures
      and photoluminescent properties of compound 1 (formula = 2HPhTT.3AgTf.3toluene)
      and compound 2 (formula = 2HPhTT.3AgTf.2THF) are described. Both 1 and 2 feature
      similar network connectivity as well as similar local coordination environments
      around the silver(I) atoms. The organizations of the guest molecules in the two
      structures are, however, quite different: In 1, the toluene molecules are
      enclathrated in isolated cavities by the host network; in 2, the THF molecules
      are confined in continuous 1D channels. Because of the large aromatic system of
      the triphenylene moiety, strong fluorescent bands (room temperature) are observed
      for HPhTT, 1 and 2, with lambda(F,max) = 447 nm for HPhTT and lambda(F,max) = 440
      nm for both 1 and 2.

PMID- 15578841
TI  - Synthesis, structure, and complexation of a large 28-mer macrocycle containing
      two binding sites for either anions or metal ions.
AB  - The "one-pot" synthesis and characterization of a large 28-mer macrocycle
      (H(4)L(2)) with oxamido units capable of complexing guest ions through oxygen or
      nitrogen donor atoms is reported. Single-crystal structure determination of
      H(8)L(2)(NO(3))(4) and (Cu(2)[H(2)L(2)](H(2)O)(2))(NO(3))(2) demonstrated that
      the macrocycle contains two sites capable of complexing two nitrate anions or two
      copper(II) ions, involving a large structural reorganization in the conformation
      of the macrocyclic framework on coordination of the copper(II) ions when compared
      to the nitrate. Electrochemical and magnetic susceptibility measurements on the
      dinuclear Cu(II) complex and the related mononuclear and trinuclear Cu(II)
      complexes derived from the related 14-mer macrocycle were carried out and
      illustrate the role of the oxamido groups in mediating metal-metal interaction
      and delocalization.

PMID- 15578842
TI  - Snapshots of a metamorphosing Cu(II) ground state in a galactose oxidase-inspired
      complex.
AB  - The novel ligand 2,6-bis[S-(3,5-di-tert-butyl-2
      hydroxyphenyl)sulfanylmethyl]pyridine (H(2)L1) and its copper(II) complex Cu(L1),
      1, were synthesized with the aim of constructing a model of the active site of
      the enzyme galactose oxidase (GOase). Cyclic voltammetry studies show that 1
      undergoes ligand-based quasi-reversible oxidations (phenolate/phenoxyl) and
      reversible metal-based reduction [copper(II)/copper(I)] similar to those of
      GOase, but at potentials much higher and lower, respectively, than those found
      for the enzyme. At room temperature, spectrophotometric titrations show that 1
      binds strongly to 1 equiv of pyridine. In frozen solutions (77 K), 1
      quantitatively binds both pyridine and ethers (e.g., 1,4-dioxane) as assessed by
      X- and Q-band EPR spectroscopy. Profound shifts in the pattern of g values
      result, from rhombic (g(1) > g(2) > g(3)) in toluene to either inverted axial
      patterns (g(1) = g(2) >> g(3)) in the presence of ethers or a near-axial pattern
      (g(1) >> g(2) > g(3)) in the presence of pyridine. Crystallographic analyses of
      the parent complex 1.MeCN, the dioxane-bridged dimer [(Cu(L1))(2)((mu-1,4)-1,4
      dioxane)].(Me(2)CO)(2) (2), and the pyridine complex [Cu(L1)(pyridine)] (3) show
      that the pyridine and ether ligands bond to copper at a sixth octahedral position
      left vacant by the pentadentate NO(2)S(2) coordination mode of L1(2-) and induce
      perturbations of its geometry. Hybrid DFT calculations based on the
      crystallographic coordinates combined with perturbation theory expressions for
      the g values of a d(9) system correlate the results from EPR spectroscopy to the
      proportions of d(x)(2)(-)(y)(2) and d(z)(2) character in the relevant copper
      centered unoccupied molecular orbital. The combination of spectroscopic,
      structural, and computational results for this set of copper(II) complexes
      provides a demonstrative example of the physical phenomena underlying rhombic EPR
      spectra of d(9) systems.

PMID- 15578843
TI  - Bending, twisting, and breaking CuCN chains to produce framework materials: the
      reactions of CuCN with alkali-metal halides.
AB  - The reactions of the low-temperature polymorph of copper(I) cyanide (LT-CuCN)
      with concentrated aqueous alkali-metal halide solutions have been investigated.
      At room temperature, KX (X = Br and I) and CsX (X = Cl, Br, and I) produce the
      addition products K[Cu(2)(CN)(2)Br].H(2)O (I), K(3)[Cu(6)(CN)(6)I(3)].2H(2)O
      (II), Cs[Cu(3)(CN)(3)Cl] (III), Cs[Cu(3)(CN)(3)Br] (IV), and
      Cs(2)[Cu(4)(CN)(4)I(2)].H(2)O (V), with 3-D frameworks in which the -(CuCN)-
      chains present in CuCN persist. No reaction occurs, however, with NaX (X = Cl,
      Br, I) or KCl. The addition compounds, I-V, reconvert to CuCN when washed. Both
      low- and high-temperature polymorphs of CuCN (LT- and HT-CuCN) are produced,
      except in the case of Cs[Cu(3)(CN)(3)Cl] (III), which converts only to LT-CuCN.
      Heating similar AX-CuCN reaction mixtures under hydrothermal conditions at 453 K
      for 1 day produces single crystals of I-V suitable for structure determination.
      Under these more forcing conditions, reactions also occur with NaX (X = Cl, Br,
      I) and KCl. NaBr and KCl cause some conversion of LT-CuCN into HT-CuCN, while
      NaCl and NaI, respectively, react to form the mixed-valence Cu(I)/Cu(II)
      compounds [Cu(II)(OH(2))(4)][Cu(I)(4)(CN)(6)], a known phase, and
      [Cu(II)(OH(2))(4)][Cu(I)(4)(CN)(4)I(2)] (VI), a 3-D framework, which contains
      infinite -(CuCN)- chains. After 3 days of heating under hydrothermal conditions,
      the reaction between KI and CuCN produces [Cu(II)(OH(2))(4)][Cu(I)(2)(CN)I(2)](2)
      (VII), in which the CuCN chains are broken into single Cu-CN-Cu units, which in
      turn are linked into chains via iodine atoms and then into layers via long Cu-C
      and Cu-Cu interactions.

PMID- 15578844
TI  - Structure and bonding of the vanadium(III) hexa-aqua cation. 1. Experimental
      characterization and ligand-field analysis.
AB  - Spectroscopic and crystallographic data are presented for salts containing the
      [V(OH(2))(6)](3+) cation, providing a rigorous test of the ability of the angular
      overlap model (AOM) to inter-relate the electronic and molecular structure of
      integer-spin complexes. High-field multifrequency EPR provides a very precise
      definition of the ground-state spin-Hamiltonian parameters, while single-crystal
      absorption measurements enable the energies of excited ligand-field states to be
      identified. The EPR study of vanadium(III) as an impurity in guanidinium gallium
      sulfate is particularly instructive, with fine-structure observed attributable to
      crystallographically distinct [V(OH(2))(6)](3+) cations, hyperfine coupling, and
      ferroelectric domains. The electronic structure of the complex depends strongly
      on the mode of coordination of the water molecules to the vanadium(III) cation,
      as revealed by single-crystal neutron and X-ray diffraction measurements, and is
      also sensitive to the isotopic abundance. It is shown that the AOM gives a very
      good account of the change in the electronic structure, as a function of
      geometric coordinates of the [V(OH(2))(6)](3+) cation. However, the ligand-field
      analysis is inconsistent with the profiles of electronic transitions between
      ligand-field terms.

PMID- 15578845
TI  - Structure and bonding of the vanadium(III) hexa-aqua cation. 2. Manifestation of
      dynamical Jahn-Teller coupling in axially distorted vanadium(III) complexes.
AB  - Ground-state spin-Hamiltonian parameters, magnetic data, and electronic Raman
      spectra of hexacoordinate vanadium(III) complexes are calculated with
      consideration to the ((3)A (3)E) e vibronic interaction and compared to
      experimental data. It is shown that the zero-field-splitting of the (3)A(g)
      (S(6)) ground term may be reduced significantly by the dynamical Jahn-Teller
      effect, particularly when the pi-anisotropy of the metal-ligand bonding
      interaction is significant, and the energy of the Jahn-Teller active vibration is
      comparable to the diagonal axial field. The dynamical Jahn-Teller effect may also
      give rise to a significant enhancement in the Raman intensity of overtones and
      higher harmonics of Jahn-Teller active vibrations, when the energies of these
      transitions fall in the proximity of intra-(3)T(1g) (O(h)) electronic Raman
      transitions. A simple method of conducting vibronic coupling calculations is
      described, employing ligand field matrices generated by angular overlap model
      calculations, which may in principle be applied to any transition metal complex.

PMID- 15578846
TI  - A chiral molecular conductor: synthesis, structure, and physical properties of
      [ET]3[Sb2(L-tart)2].CH3CN (ET = bis(ethylendithio)tetrathiafulvalene; L-tart =
      (2R,3R)-(+)-tartrate).
AB  - The salt [ET](3)[Sb(2)(L-tart)(2)].CH(3)CN (1) has been obtained by
      electrocrystallization of the organic donor bis(ethylendithio)tetrathiafulvalene
      (ET or BEDT-TTF) in the presence of the chiral anionic complex [Sb(2)(L
      tart)(2)](2-) (L-tart = (2R,3R)-(+)-tartrate). This salt crystallizes in the
      chiral space group P2(1)2(1)2(1) (a = 11.145(2) angstroms, b = 12.848(2)
      angstroms, c = 40.159(14) angstroms, V = 5750.4(14) angstroms(3), Z = 4) and is
      formed by alternating layers of the anions and of the organic radicals in a
      noncentrosymmetric alpha-type packing. This compound shows a room temperature
      electrical conductivity of approximately 1 S.cm(-1) and semiconducting behavior
      with an activation energy of approximately 85 meV. Analysis of the magnetic
      susceptibility and band structure, however, suggests that this compound should be
      a narrow band gap semiconductor.

PMID- 15578847
TI  - Structure of the amodiaquine-FPIX mu oxo dimer solution complex at atomic
      resolution.
AB  - Using NMR inversion recovery experiments and XPLOR distance restraint
      calculations, we recently deduced the structure of ferriprotoporphyrin IX (FPIX)
      heme mu oxo dimer-antimalarial drug complexes for chloroquine (CQ), quinine (QN),
      and quinidine (QD) at atomic resolution [A. Leed et al., Biochemistry 2002, 41,
      10245-55]. Using similar methods, we now report an unexpected structure for the
      complex formed between FPIX and the related drug amodiaquine (AQ). The deduced
      structure is further supported by comparing AQ chemical-shift data to restricted
      Hartree-Fock calculations. The structure further highlights the critical nature
      of quinoline drug side-chain composition in stabilizing noncovalent association
      to FPIX. Heme Fe-AQ proton distances are longer, relative to those of the CQ
      complex, and the AQ aromatic side chain seems to have a significant role in
      stabilizing the complex. Relative to the FPIX-CQ complex, a similar 2:1
      stoichiometry was determined for the AQ complex, in contrast to a 4:1
      stoichiometry previously suggested from calorimetry data. These solution
      structures add to our rapidly growing understanding of the mechanism of quinoline
      antimalarial drug action and will help elucidate the mechanism(s) of quinoline
      antimalarial drug resistance phenomena.

PMID- 15578848
TI  - Hydrothermal syntheses, crystal structures, and properties of a novel class of
      3,3',4,4'-benzophenone-tetracarboxylate (BPTC) polymers.
AB  - Three novel BPTC complexes, (H(2)BPTC)(4,4'-H(2)bpy)H(2)O (1),
      [Cd(2)Cu(HBPTC)(2)(mu(2)-4,4'-bpy)(2)(4,4'-bpy)(2)(H(2)O)(2)](n) (2), and
      [Co(3)(HBPTC)(2)(mu(2)-4,4'-bpy)(3)(H(2)O)(4)](n).2nH(2)O (3) (BPTC = 3,3',4,4'
      benzophenone-tetracarboxylate and bpy = bipyridine), were hydrothermally
      synthesized. Complex 1, which is obtained as a coproduct during the syntheses of
      complexes 2 and 3, features a 2-D layered strong hydrogen bonding network with 2
      fold interpenetration. Complex 2 has an unusual 2-D double-layered motif, which
      is linked together by Cu atoms in a face-to-face manner. It exhibits nanosized
      channels filled by 4,4'-bpy ligands. Three six-coordinated Co atoms in 3 are
      interlinked by HBPTC ligands to form a 2-D grid structure, which is further
      sustained by rigid 4,4'-bpy ligands into a 3-D open framework similar to CdSO(4)
      with the BPTC moieties situated in the tunnels. The thermal stabilities of
      complexes 1-3 were examined. The photoluminescence properties of complexes 1-2
      and temperature-dependent magnetic susceptibility for 3 were also studied.

PMID- 15578849
TI  - Comparative kinetics and mechanism of oxygen and sulfur atom transfer reactions
      mediated by bis(dithiolene) complexes of molybdenum and tungsten.
AB  - Although the kinetics and mechanism of metal-mediated oxygen atom (oxo) transfer
      reactions have been examined in some detail, sulfur atom (sulfido) transfer
      reactions have not been similarly scrutinized. The reactions [M(IV)(O-p
      C(6)H(4)X')(S(2)C(2)Me(2))(2)](1-) + Ph(3)AsQ --> [M(VI)Q(O-p
      C(6)H(4)X')(S(2)C(2)Me(2))(2)](1-) + Ph(3)As (M = Mo, W; Q = O, S) with variable
      substituent X' have been investigated in acetonitrile in order to determine the
      relative rates of oxo versus sulfido transfer at constant structure (square
      pyramidal) of the atom acceptor and of atom transfer at constant structure of the
      atom donor and metal variability of the atom acceptor. All reactions exhibit
      second-order kinetics and entropies of activation (-25 to -45 eu) consistent with
      an associative transition state. At parity of atom acceptor, k(2)(S) (0.25-0.75
      M(-1)s(-1)) > k(2)(O) (0.023-0.060 M(-1)s(-1)) with M = Mo and k(2)(S) (4.1-66.7
      M(-1)s(-1)) > k(2)(O) (1.8-9.8 M(-1)s(-1)) with M = W. At constant atom donor and
      X', k(2)(W) > k(2)(Mo) with reactivity ratios k(2)(W)/k(2)(Mo) = 78-184 (Q = O)
      and 16-89 (Q = S). Rate constants refer to 298 K. At constant M and Q, rates
      increase in the order X' = Me less, similar OMe < H < Br < COMe < CN; increasing
      electron-withdrawing propensity accelerates reaction rates. The probable
      transition state involves significant Ph(3)AsQ...M bond-making (X' rate trend)
      and concomitant As-Q bond weakening (bond energy order As-O > As-S). Orders of
      oxo and sulfido donor ability of substrates and complexes are deduced on the
      basis of qualitative reactivity properties determined here and elsewhere. This
      work complements previous studies of the reaction systems [M(IV)(O-p
      C(6)H(4)X')(S(2)C(2)Me(2))(2)](1-)/XO where the substrates are N-oxides and S
      oxides and k(2)(W) > k(2)(Mo) at constant substrate also applies. The reaction
      order of substrates is Me(3)NO > (CH(2))(4)SO > Ph(3)AsS > Ph(3)AsO. This
      research provides the first quantitative information of metal-mediated sulfido
      transfer.

PMID- 15578850
TI  - Chiral palladium template promoted asymmetric hydrophosphination reaction between
      diphenylphosphine and vinylphosphines.
AB  - An organopalladium complex containing ortho-metalated (S)-(1
      (dimethylamino)ethyl)naphthalene as the chiral auxiliary has been used to promote
      the asymmetric hydrophosphination reactions between diphenylphosphine and (E)- or
      (Z)-diphenyl-1-propenylphosphine in high regio- and stereoselectivities under
      mild conditions. Hydrophosphination of (Z)-diphenyl-1-propenylphosphine with
      diphenylphosphine gave (S)-(-)-prophos as the major product. Using the same
      chiral metal template, the corresponding hydrophosphination reaction with (E)
      diphenyl-1-propenylphosphine gave (R)-(+)-prophos predominantly. The
      hydrophosphination reactions generated the asymmetric diphosphines as bidentate
      chelates on the chiral naphthylamine palladium templates. The template products
      obtained undergo cis-trans isomerization in solution to form an equilibrium
      mixture of regioisomers. X-ray analysis of the major template products obtained
      from the hydrophosphination of (Z)-diphenyl-1-propenylphosphine reveals that the
      two regioisomers are cocrystallized in a 1:1 ratio. The naphthylamine auxiliary
      could be removed chemoselectively from the template products by treatment with
      concentrated hydrochloric acid to form the corresponding optically pure neutral
      complexes [(R)- or (S)-(prophos)PdCl(2)]. Subsequently, the (R)- and (S)-dichloro
      complexes undergo ligand displacement with aqueous cyanide to generate the
      corresponding optically pure diphosphine ligands in high yields. Mechanistic
      pathways explaining the stereoselectivity of the chiral organopalladium template
      promoted hydrophosphination reactions are also proposed.

PMID- 15578851
TI  - Electronic structure of bent titanocene complexes with chelated dithiolate
      ligands.
AB  - Gas-phase photoelectron spectroscopy and density functional theory have been
      utilized to investigate the interactions between the p orbitals of dithiolate
      ligands and d orbitals of titanium in bent titanocene complexes as minimum
      molecular models of active site features of pyranopterin Mo/W enzymes. The
      compounds Cp(2)Ti(S-S) [where (S-S) is 1,2-ethenedithiolate (S(2)C(2)H(2)), 1,
      1,2-benzenedithiolate (bdt), 2, or 1,3-propanedithiolate (pdt), 3, and Cp(-) is
      cyclopentadienyl] provide access to a formal 16-electron d(0) electronic
      configuration at the metal. A "dithiolate-folding-effect" involving an
      interaction of metal and sulfur orbitals is demonstrated in complexes with arene-
      and enedithiolates. This effect is not observed for the alkanedithiolate in
      complex 3.

PMID- 15578852
TI  - Preparation, structure characterization, and oxidation activity of ruthenium
      complexes with tripodal ligands bearing noncovalent interaction sites.
AB  - Ruthenium(II/III) complexes with tripodal tris(pyridylmethyl)amine ligands
      bearing one, two, or three pivalamide groups (MPPA, BPPA, TPPA: amide-series
      ligands) or neopentylamine ones (MNPA, BNPA, TNPA: amine-series ligands) at the 6
      position of the pyridine ring have been synthesized and structurally
      characterized. The X-ray structure analyses of the single crystals of these
      complexes reveal that they complete an octahedral geometry with the tripodal
      ligand and some monodentate ligands. The amide-series ligands prefer to form a
      Ru(II) complex, while the amine-series ones give a Ru(III) complex. In the
      presence of PhIO oxidant, the catalytic activities for epoxidation of olefins,
      hydroxylation of alkane, and dehydrogenation of alcohol have been investigated
      using the six ruthenium complexes [Ru(II)(tppa)Cl(2)] (1),
      [Ru(III)(tnpa)Cl(2)]PF(6) (2), [Ru(II)(bppa)Cl]PF(6) (3),
      [Ru(III)(bnpa)Cl(2)]PF(6) (4), [Ru(II)(mppa)Cl]PF(6) (5), and
      [Ru(III)(mnpa)Cl(2)]PF(6) (6). Among them, the amide-series complexes, 1, 3, and
      5, showed a higher epoxidation activity in comparison with the amine-series ones,
      2, 4, and 6. On the other hand, the latter showed a higher reactivity for
      hydroxylation, allylic oxidation, and C=C bond cleavage reactions compared with
      the former. Such a complementary reactivity is interpreted by the character of
      the ruthenium-oxo species involving electronically equivalent formulas, Ru(V)=O
      and Ru(IV)-O.

PMID- 15578854
TI  - Chlorocarbonyl trifluoromethanesulfonate, ClC(O)OSO2CF3: structure and
      conformational properties in the gaseous and condensed phases.
AB  - Pure chlorocarbonyl trifluoromethanesulfonate, ClC(O)OSO(2)CF(3), has been
      prepared in about 58% yield by the ambient-temperature reaction between ClC(O)SCl
      and AgCF(3)SO(3). The conformational properties of the gaseous molecule have been
      studied by vibrational spectroscopy [IR(gas), IR(matrix), and Raman(liquid)] and
      quantum chemical calculations (HF and B3LYP with 6-31+G* basis sets); in
      addition, the solid-state structure has been determined by X-ray crystallography.
      ClC(O)OSO(2)CF(3) exists in the gas phase as a mixture of trans [ClC(O) group
      trans with respect to the CF(3) group] and gauche conformers, with the trans form
      being the more abundant [66(8)% from IR(matrix) measurements]. In both
      conformers, the C=O bond of the ClC(O) group is oriented synperiplanar with
      respect to the S-O single bond. The experimental free energy difference between
      the two forms, DeltaG degrees = 0.8(2) kcal mol(-1) (IR), is slightly smaller
      than the calculated value (1.0-1.5 kcal mol(-1)). The crystalline solid at 150 K
      [monoclinic, P2(1)/n, a = 7.3951(9) angstroms, b = 24.897(3) angstroms, c =
      7.4812(9) angstroms, beta = 99.448(2) degrees, Z = 8] consists surprisingly of
      both trans and gauche forms. Whereas the more stable conformer for the more or
      less discrete molecules and the polarization effects would tend to favor the
      trans form, the packing effects would stabilize the gauche rotamer in the solid
      state.

PMID- 15578853
TI  - Solution structure and thermolysis of Cobeta-5'-deoxyadenosylimidazolylcobamide,
      a coenzyme B12 analogue with an imidazole axial nucleoside.
AB  - The solution structure of Cobeta-5'-deoxyadenosylimidazolylcobamide, Ado(Im)Cbl,
      the coenzyme B(12) analogue in which the axial 5,6-dimethylbenzimidazole (Bzm)
      ligand is replaced by imidazole, has been determined by NMR-restrained molecular
      modeling. A two-state model, in which a conformation with the adenosyl moiety
      over the southern quadrant of the corrin and a conformation with the adenosyl
      ligand over the eastern quadrant of the corrin are both populated at room
      temperature, was required by the nOe data. A rotation profile and molecular
      dynamics simulations suggest that the eastern conformation is the more stable, in
      contrast to AdoCbl itself in which the southern conformation is preferred.
      Consensus structures of the two conformers show that the axial Co-N bond is
      slightly shorter and the corrin ring is less folded in Ado(Im)Cbl than in AdoCbl.
      A study of the thermolysis of Ado(Im)Cbl in aqueous solution (50-125 degrees C)
      revealed competing homolytic and heterolytic pathways as for AdoCbl but with
      heterolysis being 9-fold faster and homolysis being 3-fold slower at 100 degrees
      C than for AdoCbl. Determination of the pK(a)'s for the Ado(Im)Cbl base-on/base
      off reaction and for the detached imidazole ribonucleoside as a function of
      temperature permitted correction of the homolysis and heterolysis rate constants
      for the temperature-dependent presence of the base-off species of Ado(Im)Cbl.
      Activation analysis of the resulting rate constants for the base-on species show
      that the entropy of activation for Ado(Im)Cbl homolysis (13.7 +/- 0.9 cal mol(-1)
      K(-1)) is identical with that of AdoCbl (13.5 +/- 0.7 cal mol(-1) K(-1)) but that
      the enthalpy of activation (34.8 kcal mol(-1)) is 1.0 +/- 0.4 kcal mol(-1)
      larger. The opposite effect is seen for heterolysis, where the enthalpies of
      activation are identical but the entropy of activation is 5 +/- 1 cal mol(-1) K(
      1) less negative for Ado(Im)Cbl. Extrapolation to 37 degrees C provides a rate
      constant for Ado(Im)Cbl homolysis of 2.1 x 10(-9) s(-1), 4.3-fold smaller than
      for AdoCbl. Combined with earlier results for the enzyme-induced homolysis of
      Ado(Im)Cbl by the ribonucleoside triphosphate reductase from Lactobacillus
      leichmannii, the catalytic efficiency of the enzyme for homolysis of Ado(Im)Cbl
      at 37 degrees C can be calculated to be 4.0 x 10(8), 3.8-fold, or 0.8 kcal mol(
      1), smaller than for AdoCbl. Thus, the bulky Bzm ligand makes at best a <1 kcal
      mol(-1) contribution to the enzymatic activation of coenzyme B(12).

PMID- 15578855
TI  - Spin-frustrated (VO)36+-triangle-sandwiching octadecatungstates as a new class of
      molecular magnets.
AB  - Spin-frustrated polyoxometalates, K(11)H[(VO)(3)(SbW(9)O(33))(2)].27H(2)O (1) and
      K(12)[(VO)(3)(BiW(9)O(33))(2)].29H(2)O (2), containing approximately equilateral
      and isosceles (VO)(3)(6+)-triangles (V(IV)...V(IV) separation of 5.4-5.5 A)
      sandwiched by two diamagnetic alpha-B nonatungstate ligands ([SbW(9)O(33)](9)(-)
      and [BiW(9)O(33)](9)(-)) with approximate D(3)(h) symmetry, are found to show
      magnetization jumps with distinct hysteresis for the S = (1)/(2) <--> S = (3)/(2)
      level crossing under fast sweeping pulsed magnetic fields (approximately 10(3)
      T/s) at T < or = 0.5 K. This unusual phenomenon is attributed to the theoretical
      prediction of half step magnetization, which is expected for an antiferromagnetic
      spin triangle with antisymmetrical Dzyaloshinky-Moriya interaction. The
      degeneracy of the S = (1)/(2) states for 1 is removed by slightly lower symmetry
      effects of triangular structure for 2. The calorimetry of 1 and 2 shows the heat
      capacity anomaly at 2 < or = T < or = 20 K which is associated with a thermal
      excitation from the S = (1)/(2) ground states to the S = (3)/(2) state at zero
      field. Zero-field splitting energies (5-7 K) between S = (1)/(2) and S = (3)/(2)
      states for 1 and 2, readily estimated by the level-crossing field for the
      magnetization, allow us to measure the hyperfine-structural 22 lines due to three
      equivalent I = (7)/(2) (51)V nuclei, the fine-structural triplet line of the S =
      (3)/(2) excited state, and the g anisotropy on the high-frequency ESR spectra.
      The spin-frustrated (VO)(3)(6+)-triangle for 1 and 2 is a good model of the
      magnetization between pure quantum states S = (1)/(2) and (3)/(2) and provides a
      new class of single-molecule magnets.

PMID- 15578856
TI  - Preparation of 1-p-halophenyl and 1-p-biphenylyl substituted
      monocarbadodecaborate anions [closo-1-Ar-CB11H11]- by insertion of
      arylhalocarbenes into [nido-B11H14]-.
AB  - In the presence of a strong base, benzal chloride (C(6)H(5)CHCl(2)) and its p
      substituted derivatives react with [nido-B(11)H(14)](-) to yield [closo-1-p-X
      C(6)H(4)-CB(11)H(11)](-) (X = H, F, Cl, Br, I, Ph), presumably by insertion of an
      arylhalocarbene and oxidation. On a 1-g scale, the yields are 30-40%, except in
      the case of p-iodobenzal chloride, which yields only 12% of the insertion
      product.

PMID- 15578857
TI  - Structural and conformational properties of fluoroformic acid anhydride,
      FC(O)OC(O)F.
AB  - The conformational properties and geometric structures of fluoroformic acid
      anhydride, FC(O)OC(O)F, have been studied by vibrational spectroscopy, gas
      electron diffraction (GED), single-crystal X-ray diffraction, and quantum
      chemical calculations (HF, MP2, and B3LYP methods with 6-31G* and B3LYP/6-311+G*
      basis sets). Satellite bands in the IR matrix spectra, which increase in
      intensity when the matrix gas mixture is heated prior to deposition as a matrix,
      indicate the presence of two conformers at room temperature. According to the
      electron diffraction analysis, the prevailing conformer is of C(2) symmetry with
      both C=O bonds synperiplanar with respect to the opposite C-O bond ([sp, sp]
      conformer). The minor conformer [15(5)% from IR matrix and 6(11)% from GED] is
      predicted by quantum chemical calculations to possess an [sp, ac] structure.
      FC(O)OC(O)F crystallizes in the orthorhombic system in the space group
      P2(1)2(1)2(1) with a = 6.527(1) angstroms, b = 7.027(1) angstroms, and c =
      16.191(1) angstroms and four formula units per unit cell. In the crystal, only
      the [sp, sp] conformer is present, and the structural parameters are very similar
      to those determined by GED.

PMID- 15578858
TI  - Structural, magnetic, and transport properties of the SrTi1-xCoxO3-delta
      perovskite (0 < or = x < or = 0.9).
AB  - The series of the SrTi(1-x)Co(x)O(3-delta) polycrystalline samples has been
      prepared via solid-state reaction in air. The structural study shows that a solid
      solution exists for all compositions, such as 0 < or = x < or = 0.9, which
      discards the presence of ferromagnetic and metallic cobalt clusters for the low
      level of cobalt substitution. The existence of systematic extra peaks on the
      electron diffraction patterns for x > 0.5 indicates that the oxygen vacancy
      ordering is responsible for the superstructures (2a(p) x 2a(p) x 4a(p), where the
      subscript "p" refers to the perovskite subcell). The oxygen nonstoichiometry is
      confirmed by thermogravimetric analysis. The magnetic properties reveal a maximum
      in the magnetic moment per mole of cobalt for x approximately 0.10. However, the
      clear lack of strong ferromagnetism does not suggest that a diluted magnetic
      semiconductor (DMS)-type behavior is induced in SrTiO(3) as Co is substituted for
      Ti. The transport properties along the SrTi(1-x)Co(x)O(3-delta) line are
      explained by considering the substitution of a Co(3+)/Co(4+) mixed valency, which
      decreases the room-temperature resistivity by at least 5 orders of magnitude as
      one goes from SrTi(0.9)Co(0.1)O(3-delta) to SrTi(0.1)Co(0.9)O(3-delta).

PMID- 15578859
TI  - Can the bis(diboranyl) structure of B(4)H(10) be observed? The story continues.
AB  - Pathways for the conversion of the unknown bis(diboranyl) isomer of
      tetraborane(10) (B(4)H(10)) to the known arachno isomer have been determined for
      the first time with the use of an electron correlation ab initio quantum chemical
      method and without the use of constraints in determination of the transition
      structures. Two isomers of tetraborane(10), one new, with a pentacoordinated
      boron atom have been found on the theoretical potential energy surface. Several
      other pathways for molecular rearrangement of tetraborane(10) have also been
      characterized. The theoretical method was MP2 theory with the 6-31G(d,p) basis
      set. The most likely pathway for the conversion of the bis(diboranyl) isomer of
      tetraborane(10) to the arachno isomer is a concerted pathway with two
      pentacoordinated intermediates. The highest energy transition state for this
      pathway lies 27.7 kcal/mol above the bis(diboranyl) isomer. At the same level of
      the theory, the bis(diboranyl) isomer lies 9.2 kcal/mol above the known arachno
      isomer. The two isomers with a pentacoordinated boron atom lie 12.5 and 13.1
      kcal/mol above the arachno isomer.

PMID- 15578860
TI  - Alkynyldiphenylphosphine d8 (Pt, Rh, Ir) complexes: contrasting behavior toward
      cis-[Pt(C6F5)2(THF)2].
AB  - The synthesis and characterization of a series of mononuclear d(8) complexes with
      at least two P-coordinated alkynylphosphine ligands and their reactivity toward
      cis-[Pt(C(6)F(5))(2)(THF)(2)] are reported. The cationic [Pt(C(6)F(5))(PPh(2)C
      triple-bond CPh)(3)](CF(3)SO(3)), 1, [M(COD)(PPh(2)C triple-bond CPh)(2)](ClO(4))
      (M = Rh, 2, and Ir, 3), and neutral [Pt(o-C(6)H(4)E(2))(PPh(2)C triple-bond
      CPh)(2)] (E = O, 6, and S, 7) complexes have been prepared, and the crystal
      structures of 1, 2, and 7.CH(3)COCH(3) have been determined by X-ray
      crystallography. The course of the reactions of the mononuclear complexes 1-3, 6,
      and 7 with cis-[Pt(C(6)F(5))(2)(THF)(2)] is strongly influenced by the metal and
      the ligands. Thus, treatment of 1 with 1 equiv of cis-[Pt(C(6)F(5))(2)(THF)(2)]
      gives the double inserted cationic product [Pt(C(6)F(5))(S)mu
      (C(Ph)=C(PPh(2))C(PPh(2))=C(Ph)(C(6)F(5)))Pt(C(6)F(5))(PPh(2)C triple-bond
      CPh)](CF(3)SO(3)) (S = THF, H(2)O), 8 (S = H(2)O, X-ray), which evolves in
      solution to the mononuclear complex [(C(6)F(5))(PPh(2)C triple-bond
      CPh)Pt(C(10)H(4)-1-C(6)F(5)-4-Ph-2,3-kappaPP'(PPh(2))(2))](CF(3) SO(3)), 9 (X
      ray), containing a 1-pentafluorophenyl-2,3-bis(diphenylphosphine)-4
      phenylnaphthalene ligand, formed by annulation of a phenyl group and loss of the
      Pt(C(6)F(5)) unit. However, analogous reactions using 2 or 3 as precursors afford
      mixtures of complexes, from which we have characterized by X-ray crystallography
      the alkynylphosphine oxide compound [(C(6)F(5))(2)Pt(mu-kappaO:eta(2)-PPh(2)(O)C
      triple-bond CPh)](2), 10, in the reaction with the iridium complex (3). Complexes
      6 and 7, which contain additional potential bridging donor atoms (O, S), react
      with cis-[Pt(C(6)F(5))(2)(THF)(2)] in the appropriate molar ratio (1:1 or 1:2) to
      give homo- bi- or trinuclear [Pt(PPh(2)C triple-bond CPh)(mu-kappaE-o
      C(6)H(4)E(2))(mu-kappaP:eta(2)-PPh(2)C triple-bond CPh)Pt(C(6)F(5))(2)] (E = O,
      11, and S, 12) and [(Pt(mu(3)-kappa(2)EE'-o-C(6)H(4)E(2))(mu-kappaP:eta(2)
      PPh(2)C triple-bond CPh)(2))(Pt(C(6)F(5))(2))(2)] (E = O, 13, and S, 14)
      complexes. The molecular structure of 14 has been confirmed by X-ray diffraction,
      and the cyclic voltammetric behavior of precursor complexes 6 and 7 and
      polymetallic derivatives 11-14 has been examined.

PMID- 15578861
TI  - Poisoning due to chlorophenoxy herbicides.
AB  - Chlorophenoxy herbicides are used widely for the control of broad-leaved weeds.
      They exhibit a variety of mechanisms of toxicity including dose-dependent cell
      membrane damage, uncoupling of oxidative phosphorylation and disruption of
      acetylcoenzyme A metabolism. Following ingestion, vomiting, abdominal pain,
      diarrhoea and, occasionally, gastrointestinal haemorrhage are early effects.
      Hypotension, which is common, is due predominantly to intravascular volume loss,
      although vasodilation and direct myocardial toxicity may also contribute. Coma,
      hypertonia, hyperreflexia, ataxia, nystagmus, miosis, hallucinations,
      convulsions, fasciculation and paralysis may then ensue. Hypoventilation is
      commonly secondary to CNS depression, but respiratory muscle weakness is a factor
      in the development of respiratory failure in some patients. Myopathic symptoms
      including limb muscle weakness, loss of tendon reflexes, myotonia and increased
      creatine kinase activity have been observed. Metabolic acidosis, rhabdomyolysis,
      renal failure, increased aminotransferase activities, pyrexia and
      hyperventilation have been reported. Substantial dermal exposure to 2,4
      dichlorophenoxy acetic acid (2,4-D) has led occasionally to systemic features
      including mild gastrointestinal irritation and progressive mixed sensorimotor
      peripheral neuropathy. Mild, transient gastrointestinal and peripheral
      neuromuscular symptoms have occurred after occupational inhalation exposure. In
      addition to supportive care, urine alkalinization with high-flow urine output
      will enhance herbicide elimination and should be considered in all seriously
      poisoned patients. Haemodialysis produces similar herbicide clearances to urine
      alkalinization without the need for urine pH manipulation and the administration
      of substantial amounts of intravenous fluid in an already compromised patient.

PMID- 15578862
TI  - Assessment of bronchial responsiveness following exposure to inhaled occupational
      and environmental agents.
AB  - Inhalation of a range of agents can result in airway inflammation and/or
      irritation. This may result in occupational asthma or reactive airways
      dysfunction syndrome. Reactive airways dysfunction syndrome follows a single
      large exposure to a chemical agent but is now frequently embraced under the wider
      term of irritant-induced asthma, a term that also includes asthma due to
      persistent, lower dose irritant exposures. Bronchial hyperresponsiveness is a
      hallmark of both occupational asthma and reactive airways dysfunction syndrome,
      although some patients with occupational asthma may occasionally have typical
      clinical features without increased bronchial hyperresponsiveness. Following
      removal of the causal agent in occupational asthma, bronchial hyperresponsiveness
      generally returns towards normal over a 2-year period, although some individuals
      demonstrate increased bronchial hyperresponsiveness for longer. Measurement of
      specific bronchial hyperresponsiveness to the primary causal agent in
      occupational asthma is used diagnostically but not for assessing prognosis.
      Bronchial hyperresponsiveness to inhaled methacholine can be measured across
      individual workshifts to assess work-related change. It may also be measured at
      the end of a work period when exposure has occurred, and compared with values
      following a period away from work. There have been no direct, systematic
      comparisons of changes in methacholine responsiveness in the diagnosis of
      occupational asthma compared with the more frequently used serial peak flow
      measurements. Patients with reactive airways dysfunction syndrome classically
      exhibit non-specific bronchial hyperresponsiveness, which can be readily measured
      by evaluating responses to inhaled methacholine. Bronchial hyperresponsiveness in
      reactive airways dysfunction syndrome can persist for many years after initial
      exposure and serial changes can be used to assess recovery and subsequent
      disability over time.

PMID- 15578863
TI  - Glaucopsia: an occupational ophthalmic hazard.
AB  - Glaucopsia is a transient disturbance of vision that results from the development
      of corneal epithelial oedema and associated microcysts produced by exposure to
      the vapour of certain industrial chemicals, notably aliphatic, alicyclic and
      heterocyclic amines. After a latent period of a few hours of exposure, there is
      typically a blurring of vision, objects take on a blue-grey appearance and halos
      develop around bright objects. Corneal changes can be seen on biomicroscopy and
      corneal thickness increase is measurable by pachymetry. At concentrations higher
      than threshold values, visual acuity may be decreased, but contrast sensitivity
      is a better measure of visual effects. On vacating the causative vapour, vision
      returns to normal in a few hours without leaving permanent ocular sequelae.
      Vapour concentration of the causative amine is a major factor in the development
      of glaucopsia, and a concentration-effect relationship is usually evident. A
      correlation exists between the vapour concentration, degree of corneal oedema,
      corneal thickness and subjective symptoms, which permits no-effect and threshold
      effect concentrations to be determined. The disturbance of vision is a nuisance
      factor and this may impair work efficiency, predispose to physical accidents and
      hinder the performance of coordinated tasks (e.g. driving). As a consequence,
      development of glaucopsia is considered a hazard and is thus an important
      consideration in assessing workplace safety. From a knowledge of threshold and no
      effect concentrations, a workplace permissible vapour exposure concentration can
      be developed along with industrial hygiene precautionary measures.

PMID- 15578864
TI  - Does occupational exposure to organic solvents affect colour discrimination?
AB  - This review assesses the evidence regarding the effects of occupational exposure
      to organic solvents on colour discrimination and investigates exposure-response
      relationships and reversibility. This review also considers the current state of
      knowledge of the possible mechanisms underlying changes in colour vision, and the
      human health significance of any reported changes. Among the commonly used
      organic solvents, styrene has been investigated the most thoroughly. Studies of
      styrene-exposed workers in Germany, Italy and Japan provide a sufficiently
      consistent body of evidence to support a robust conclusion that styrene does
      cause an impairment of colour discrimination relative to age-matched controls.
      Generally, the impairment of colour discrimination observed in styrene-exposed
      workers tends to be of the tritan (blue-yellow) type, although some cases of red
      green impairment have also been found. The limited information available on
      exposure-response relationships indicates that the effects on colour
      discrimination would not be expected at 8-hour time weighted average (8 h TWA)
      exposures <20 ppm, although a precise threshold cannot be determined. The data on
      reversibility are limited and inconclusive. The results from the most rigorous
      study in which this aspect was investigated point to a reversibility of effects
      after a 4-week exposure-free period, whereas results from a study with
      limitations suggest a persistence of effect. The effects of toluene,
      tetrachloroethylene or mixed solvent exposure have also been investigated,
      although the information available is generally less reliable than for styrene.
      For toluene, it can be confidently concluded that this solvent does not have an
      acute effect on colour discrimination, even when exposures are relatively high
      (50-150 ppm 8 h TWA, and 290-360 ppm 30 minutes TWA). However, studies are
      inconclusive on whether long-term or repeated exposure to toluene can cause a
      persistent impairment of colour discrimination. There are few studies that have
      specifically investigated the effects of tetrachloroethylene on colour
      discrimination. Among these studies, none has examined the potential for any
      acute effects of this solvent vapour. A large-scale study in Japanese workers
      showed no effects of long-term exposure to tetrachloroethylene concentrations in
      the region of 12-13 ppm. However, the test methodology used was relatively
      insensitive to changes in colour discrimination, hence the results do not provide
      reassurance for an absence of subtle effects. A study in Italian dry-cleaners
      suggested a slight impairment of colour discrimination relative to controls,
      associated with relatively low exposures to tetrachloroethylene (mean 8 h TWA
      exposure approximately 6 ppm). The studies concerning the effects of mixed
      solvent exposure on colour discrimination are based on workers exposed to
      solvents in paints and lacquers, workers from the printing and petrochemical
      industries, people working in or living near to microelectronics factories and
      children exposed to solvents prenatally. However, these studies are subject to
      design limitations or methodological irregularities, such that no conclusions
      regarding the effects of mixed solvent exposure on colour discrimination can be
      drawn. Overall, the only credible evidence for an effect of solvents on colour
      discrimination derives from the studies on styrene. Because of limitations in the
      data for other solvents it is not possible to determine whether the evidence for
      styrene reflects a generic property of solvents. The mechanisms of styrene
      induced effects on colour discrimination have not been properly investigated and
      can only be the subject of speculation. One conclusion that can be drawn is that
      pathological changes to the ocular system, such as changes to the lens, are
      unlikely to be involved. This is because there is an absence of convincing
      evidence for such changes from medical examinations conducted in epidemiological
      studies of solvent-exposed workers. Also, it seems unlikely that effects on
      colour discrimination are a nonspecific consequence of more generalised CNS
      depression, given that styrene-induced effects on colour discrimination appear to
      occur below the threshold for narcotic effects. The effects of styrene on colour
      discrimination are subtle and involve an impairment of the ability to
      discriminate accurately between closely related shades of the same colour rather
      than 'colour blindness'. There is no valid basis for using colour discrimination
      as a marker for other forms of solvent-induced neurotoxicity.

PMID- 15578865
TI  - Toxicological and immunological aspects of occupational latex allergy.
AB  - Latex allergy continues to be an important occupational health problem as latex
      products are used increasingly worldwide, particularly in healthcare. Although
      there are few epidemiological studies on the incidence of latex allergy, there
      has been an increase in the number of case reports over the last 10 years and,
      based on skin-prick tests, estimates of prevalence of latex allergy in healthcare
      workers range from 2% to 17%. The allergic health effects arise either from the
      latex proteins, generally causing a type I immediate hypersensitivity reaction,
      or from the chemicals added to latex during processing, causing a type IV delayed
      hypersensitivity reaction. Clinical manifestations of latex allergy depend on the
      route of exposure and occur by direct contact either with skin or mucosa, or by
      inhalation. The diagnosis of latex allergy is based on the history, skin tests,
      serological tests and challenge tests. Thirteen latex allergens have been
      identified and isolated so far from natural rubber latex. They differ in their
      potential to elicit immunological responses in individuals allergic to latex and
      thus have been designated as major or minor allergens. In latex gloves,
      cornstarch powder used as a donning agent carries latex proteins, thereby
      increasing inhalational and mucosal exposure to latex proteins. There also
      appears to be a positive correlation between protein content and allergenicity of
      gloves. The use of powder-free, low-protein gloves is effective in reducing
      symptoms and markers of sensitisation. Alternatives to latex gloves, such as
      nitrile or vinyl gloves are available but may be inferior in respect to manual
      dexterity and biological impermeability.

PMID- 15578867
TI  - Use of polymerase chain reaction to diagnose tubercular arthritis from joint
      tissues and synovial fluid.

PMID- 15578869
TI  - Virtual microscopy as a tool for proficiency testing in cytopathology.

PMID- 15578871
TI  - Financial conflict of interest?

PMID- 15578873
TI  - Immunosuppressants testing in transplantation.

PMID- 15578874
TI  - Adding pharmacogenetics to the clinical laboratory: narrow therapeutic index
      medications as a place to start.

PMID- 15578876
TI  - The -omics era and its impact.
AB  - OBJECTIVE: To review the advances in clinically useful molecular biologic
      techniques and to identify their applications, as presented at the 12th Annual
      William Beaumont Hospital DNA Symposium. DATA SOURCES: The 7 manuscripts
      submitted were reviewed and their major findings were compared with literature on
      the same or related topics. STUDY SELECTION: Manuscripts address the use of
      molecular techniques in the detection of severe acute respiratory syndrome (SARS)
      and bacterial ribosome mutations, which may lead to ribosome-targeted drug
      resistance; pharmacogenomics as a clinical laboratory service and example of
      warfarin dosing using CYP2C9 mutation analysis; definition of the potential of
      cytosine arabinoside incorporation into DNA to disrupt transcription using an in
      vitro model of oligonucleotides; use of laser capture microdissection to isolate
      solid tumor cells free of nontumor cells; and molecular methods used to classify
      lymphomas. DATA SYNTHESIS: Two current issues related to the use of molecular
      tests in the clinical laboratories are (1) decentralization of molecular-based
      testing to a variety of nonmolecular laboratories and (2) need for wider
      acceptance of molecular-based testing through its incorporation in clinical
      practice guidelines. Molecular methods have had a major impact on infectious
      disease through the rapid identification of new infectious agents, SARS, and the
      characterization of drug resistance. Pharmacogenomics identifies the genetic
      basis for heritable and interindividual variation in response to drugs. The
      incorporation of the nucleoside analog, cytosine arabinoside, into DNA leads to
      local perturbation of DNA structure and reduces the ability of transcription
      factors to bind to their specific DNA binding elements as measured by
      electrophoretic mobility shift assays. Laser capture microdissection of tumor
      cells can provide an adequate number of cells for whole genome amplification.
      Gene expression microassay profiles of various lymphomas have modified
      classification systems and predict prognosis and response to therapy.
      CONCLUSIONS: The current -omics era will continue to emphasize the use of
      microarrays and database software for genomic, transcriptomic, and proteomic
      screening to search for a useful clinical assay. The number of molecular
      pathologic techniques will expand as additional disease-associated mutations are
      defined.

PMID- 15578877
TI  - Severe acute respiratory syndrome: overview with an emphasis on the Toronto
      experience.
AB  - OBJECTIVE: To provide an overview of the severe acute respiratory syndrome (SARS)
      outbreak in Toronto, Ontario, which experienced the largest outbreak outside
      Asia, and to review what has been learned during the past year. DATA SOURCES:
      MEDLINE search of all studies related to SARS, including review of the Centers
      for Disease Control and Prevention, World Health Organization (WHO), and Health
      Canada Web sites. DATA SYNTHESIS: During the SARS outbreak in Toronto, 438 people
      had been diagnosed as having suspected or probable SARS and 44 people died.
      Elderly people and those with comorbid illnesses were at greatest risk of
      complications or death. Transmission was via direct contact with respiratory
      secretions. The use of gloves, gowns, N95 masks, and eye protection was effective
      in preventing transmission. No transmission occurred before symptom onset or
      after recovery. Serologic tests suggest that antibodies may not appear until 28
      days after illness onset. Molecular tests give their greatest yield during the
      second week of illness. The value of ribavirin treatment remains questionable.
      The combination of interferon plus corticosteroids appears to be better than
      corticosteroids alone. Postmortem examination revealed pulmonary edema and
      evidence of diffuse alveolar damage. Very few morphological changes were noted in
      other organs despite the presence of viral RNA as detected by polymerase chain
      reaction. CONCLUSION: On July 5, 2003, the WHO declared that the SARS outbreak
      was over. Since then, new cases of SARS have been reported in Asia. With global
      travel, the disease can rapidly spread throughout the world. Therefore, we must
      remain vigilant to prevent another pandemic.

PMID- 15578878
TI  - Combinatorial genetic technology for the development of new anti-infectives.
AB  - CONTEXT: We previously developed a novel technology known as instant evolution
      for high-throughput analysis of mutations in Escherichia coli ribosomal RNA.
      OBJECTIVE: To develop a genetic platform for the isolation of new classes of anti
      infectives that are not susceptible to drug resistance based on the instant
      evolution system. DESIGN: Mutation libraries were constructed in the 16S rRNA
      gene of E coli and analyzed. In addition, the rRNA genes from a number of
      pathogenic bacteria were cloned and expressed in E coli. The 16S rRNA genes were
      incorporated into the instant-evolution system in E coli. SETTING: The Department
      of Biological Sciences, Wayne State University, Detroit, Mich. MAIN OUTCOME
      MEASURES: Ribosome function was assayed by measuring the amount of green
      fluorescent protein produced by ribosomes containing mutant or foreign RNA in
      vivo. RESULTS: We have developed a new combinatorial genetic technology (CGT)
      platform that allows high-throughput in vivo isolation and analysis of rRNA
      mutations that might lead to drug resistance. This information is being used to
      develop anti-infectives that recognize the wild type and all viable mutants of
      the drug target. CGT also provides a novel mechanism for identifying new drug
      targets. CONCLUSIONS: Antimicrobials produced using CGT will provide new
      therapies for the treatment of infections caused by human pathogens that are
      resistant to current antibiotics. The new therapeutics will be less susceptible
      to de novo resistance because CGT identifies all mutations of the target that
      might lead to resistance during the earliest stages of the drug discovery
      process.

PMID- 15578879
TI  - Effect of polymorphisms in the cytochrome P450 CYP2C9 gene on warfarin
      anticoagulation.
AB  - CONTEXT: Warfarin is a widely used anticoagulant with efficacy in treatment and
      prevention of thrombosis. Patient management, however, is difficult because of
      interindividual variation in response to standard doses due to significant
      differences in metabolic rates. Warfarin metabolism is under genetic control,
      involving primarily the CYP2C9 gene encoding the enzyme that catalyzes the
      conversion of warfarin to inactive metabolites. OBJECTIVE: Several polymorphisms
      of CYP2C9 have been reported; the variant alleles *2 and *3 have decreased
      enzymatic activity. The objective of this case study is to investigate the
      relationship between CYP2C9 genotype and warfarin anticoagulation. DESIGN: A case
      of deep vein thrombosis treated with the standard warfarin dose is investigated
      for intensity of anticoagulation and CYP2C9 genotype; the case illustrates the
      relationship between CYP2C9 variant and overanticoagulation with subsequent
      bleeding complication. RESULTS: The patient's genotype, CYP2C9*1*3, correlated
      with an exaggerated anticoagulant response during the initiation of warfarin
      therapy at standard dose, and a bleeding episode ensued. Based on heterozygosity
      for the *3 variant allele, it was recommended that the patient be maintained on a
      low-dose warfarin regimen. CONCLUSIONS: The practical implications of identifying
      genetic risk factors that lead to overanticoagulation are multiple. Genotype
      knowledge of the CYP2C9 variant alleles may help the clinician to individualize
      warfarin therapy with the ultimate goals of shortening the initial period of
      induction therapy, reaching a stable maintenance dose earlier, and minimizing
      bleeding complications in patients who are high responders and need lower
      warfarin doses.

PMID- 15578880
TI  - Cytosine arabinoside substitution decreases transcription factor-DNA binding
      element complex formation.
AB  - CONTEXT: The pyrimidine nucleoside analog, cytosine arabinoside (Ara-C), is an
      effective therapeutic agent for acute leukemia. The phosphorylated triphosphate,
      cytosine arabinoside triphosphate, competes with deoxycytosine triphosphate as a
      substrate for incorporation into DNA. Once incorporated into DNA, it inhibits DNA
      polymerase and topoisomerase I and modifies the tertiary structure of DNA.
      OBJECTIVE: To determine if the substitution of Ara-C for cytosine in double
      stranded oligonucleotides that contain 4 specific transcription factor binding
      sites (TATA, GATA, C/EBP, and AP-2alpha) alters transcription factor binding to
      their respective DNA binding elements. DESIGN: Transcription factors were
      obtained from nuclear extracts from human promyelocytic leukemia HL-60 cells.
      [32P]-end-labeled double-stranded oligonucleotides that contained 1 or 2 specific
      transcription factor binding sites with or without Ara-C substitution for
      cytosine were used to assess transcription factor binding by electrophoretic
      mobility shift assay. RESULTS: The substitution of Ara-C for cytosine within and
      outside the transcription factor binding element (AP-2alpha, C/EBP), outside the
      binding element only (GATA, TATA), or within the binding element only (AP-2alpha)
      all result in a reduction in transcription factor binding to their respective DNA
      binding element. CONCLUSION: The reduction of the binding capacity of
      transcription factors with their respective DNA binding elements may depend on
      structural changes within oligonucleotides induced by Ara-C incorporation. This
      altered binding capacity of transcription factors to their DNA binding elements
      may represent one mechanism for Ara-C cytotoxicity secondary to inhibition of
      transcription of new messenger RNAs and, subsequently, translation of new
      proteins.

PMID- 15578881
TI  - Microdissection techniques for molecular testing in surgical pathology.
AB  - OBJECTIVE: To describe the techniques for microdissection of paraffin-embedded
      and frozen tissue sections for the use in molecular applications. DATA SOURCES:
      Original research papers and review papers and the authors' personal experiences.
      DATA SYNTHESIS: Manual and laser-capture microdissection are described in detail,
      with specific protocols for sample preparation and instructions for performing
      the microdissection. A section addressing frequently asked questions is also
      included. CONCLUSIONS: Microdissection is a technique that is very useful both in
      the research setting and for clinical molecular testing in paraffin-embedded
      tissue samples. The available techniques range from simple and inexpensive
      (manual microdissection) to complex and expensive (laser-capture
      microdissection). All of the techniques, however, require the user to be familiar
      with microscopy and histology.

PMID- 15578882
TI  - Molecular diagnostics on lymphoid malignancies.
AB  - CONTEXT: Molecular diagnostics for lymphoid malignancies traditionally has
      focused on helping to provide a diagnosis on a tissue sample. The field has
      undergone substantial technical and conceptual evolution during the past 2
      decades, and its role has expanded to new arenas, such as monitoring disease
      activities and detecting alterations in genes that are known to have a
      significant impact on disease outcome. OBJECTIVE: To review the advances in
      molecular diagnostics on lymphoid malignancies, including recent developments
      that may facilitate the development of mechanism-based diagnosis for
      individualized therapy. DESIGN: The development of molecular diagnostics in
      lymphoid malignancies is briefly reviewed with emphasis on the recent use of gene
      expression profiling for identifying important diagnostic and prognostic
      signatures. RESULTS: Genome-scale investigations are becoming technically
      feasible and have provided promising results in the identification of new disease
      entities and new, molecularly defined prognosticators. This development can
      potentially revolutionize diagnostic medicine in the near future. As new genes or
      genetic pathways that affect the clinical and biologic behavior of tumors are
      defined and can be readily assayed, molecular diagnostics will be expected to
      provide this relevant information. Ideally, therapy will be based on this
      information, delivering the most appropriate treatment with the least toxicity.
      CONCLUSIONS: Molecular diagnostics in the future will be moving toward a
      mechanism-based diagnosis for individualized therapy.

PMID- 15578883
TI  - Salivary adenocarcinoma, not otherwise specified: a collection of orphans.
AB  - CONTEXT: Salivary adenocarcinoma, not otherwise specified, refers to gland
      forming malignancies that do not satisfy the diagnostic requirements of other
      "named" malignancies. OBJECTIVE: To review the features of 11 patients with
      salivary adenocarcinoma, not otherwise specified. To also compare the diagnostic
      frequencies of 2 databases, one from the Mount Sinai Medical Center (New York,
      NY), the other from the Shanghai Ninth People's Hospital (Shanghai, People's
      Republic of China). DESIGN: Pathology files were searched to establish a database
      of salivary tumors. All available hematoxylin-eosin- stained slides from the
      resection specimens diagnosed as either adenocarcinoma, not otherwise specified,
      or with vague or unusual diagnoses (eg, probable carcinoma-ex-pleomorphic
      adenoma) were pulled from our files and reexamined. Dates of death were confirmed
      with the Social Security Death Index. RESULTS: We identified 11 patients with
      salivary adenocarcinoma, not otherwise specified, ranging in age from 49 to 80
      years (median, 67 years), with a male preponderance. The parotid gland was the
      most common site of tumor origin. Ten of these tumors were high grade, and 1 was
      intermediate grade. Two patients were diagnosed at stage II, while the remaining
      patients were diagnosed at stage III or IV. Histologically, all tumors were
      invasive, with variable glandular differentiation and diverse architectural
      patterns. The diverse cytologic tumor cell types included cuboidal, columnar,
      epithelioid, polygonal, oncocytoid, clear, melanoma-like, mucinous, sebaceous,
      and plasmacytoid. Four patients died after 4 to 27 months (mean, 15 months), 1
      patient is alive with disease at 12 months, 1 patient is disease-free at 14
      years, and 3 patients remain disease-free after short follow-ups (10, 12, and 12
      months). One patient had surgery just recently, and the remaining patient had no
      follow-up. CONCLUSIONS: Salivary adenocarcinoma, not otherwise specified, is an
      aggressive, high-grade malignancy, with a predisposition for the parotid gland.
      It is characterized by cytologic and architectural diversity and an invasive
      growth pattern.

PMID- 15578884
TI  - The value of fluorescence in situ hybridization and polymerase chain reaction in
      the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration.
AB  - CONTEXT: Molecular genetic analyses have been predicted to improve the diagnostic
      accuracy of fine-needle aspiration of B-cell non-Hodgkin lymphoma. OBJECTIVE: To
      determine the value of routine molecular genetic assays, polymerase chain
      reaction (PCR) and fluorescence in situ hybridization (FISH), in the diagnosis of
      B-cell non-Hodgkin lymphoma by fine-needle aspiration (FNA). DESIGN: A
      multiparametric method, including cytology, flow cytometry, PCR, and FISH, was
      prospectively evaluated in the diagnosis of B-cell non-Hodgkin lymphoma by FNA.
      Aspirates from 30 consecutive patients with suspected hematolymphoid malignancies
      were collected. All aspirates were triaged through a uniform program including
      cell-size analysis, B- and T-cell clonality studies, flow cytometric
      immunophenotyping, and bcl-1 and bcl-2 gene rearrangements by PCR and FISH. After
      completion of FNA evaluations, FNA results were compared with diagnoses from
      prior or subsequent surgical biopsies. RESULTS: Monoclonal B-cell populations
      were detected in 18 of 20 B-cell non-Hodgkin lymphomas by flow cytometry and PCR.
      bcl-1 gene rearrangement was detected in 2 of 2 cases of mantle cell lymphoma.
      bcl-2 rearrangement was detected in 5 cases including 4 of 4 low-grade follicular
      lymphomas and 1 transformed follicular lymphoma. By incorporating the results of
      molecular genetic and ancillary diagnostics, a definitive classification was
      reached in 12 cases of B-cell non-Hodgkin lymphoma by FNA, including all cases of
      low-grade follicular lymphoma (4/4) and mantle cell lymphoma (2/2) and
      approximately 50% of small lymphocytic lymphoma (2/4) and large B-cell lymphoma
      (4/8). Ten of the 12 cases with a final classification reached by FNA had either
      prior or follow-up surgical biopsies, and all 10 cases showed agreement between
      the diagnoses rendered on FNA and surgical biopsies. CONCLUSIONS: With proper
      handling and management of specimens, FNA can routinely provide samples adequate
      for molecular genetic studies, in addition to cytomorphology and flow cytometry,
      making it possible to consistently render accurate and definitive diagnoses in a
      subset of B-cell non-Hodgkin lymphomas. By incorporating FISH and PCR methods,
      FNA may assume an expanded role for the primary diagnosis of B-cell non-Hodgkin
      lymphoma.

PMID- 15578885
TI  - Cystic nephroma: a histologic and immunohistochemical study of 10 cases.
AB  - CONTEXT: Cystic nephroma is a rare and controversial benign multicystic renal
      tumor. While the clinical, radiologic, and histologic features of cystic nephroma
      are well described, the immunohistochemical features are not. The role of
      immunohistochemistry in the differential diagnosis, which includes multicystic
      renal cell carcinoma, is also unknown. OBJECTIVE: To define the histologic and
      immunohistochemical features of cystic nephroma. DESIGN: Ten cases of cystic
      nephroma diagnosed at 2 institutions during a period of 10 years were stained
      with an immunohistochemical panel consisting of 20 immunostains. RESULTS: Median
      age at diagnosis was 61 years, with a range from 31 to 79 years. The female-to
      male ratio was 9:1. Grossly, the tumors were multicystic masses without solid
      nodules. Histologic features included cysts lined by flat, cuboidal, or hobnail
      epithelium and septa variably lined by fibrous (10/10 cases) and/or ovarian-like
      (7/10 cases) stroma. Corpus albicans-like acellular hyalinized structures were
      noted in the septa in 9 of 10 cases. The cyst epithelium showed consistent
      positivity for distal tubule/collecting duct markers (cytokeratin 19, cytokeratin
      AE1/AE3, epithelial membrane antigen) and variable positivity for proximal tubule
      markers (alpha1-antitrypsin, lysozyme, CD15, CD10). The ovarian-like stroma
      (present in 7/10 cases) stained positively for progesterone receptors (6/7 cases)
      and estrogen receptors (4/7 cases). CONCLUSIONS: Our immunohistochemical findings
      confirm a previous report of both distal tubule/collecting duct and proximal
      tubule differentiation in cystic nephroma. Stromal estrogen and/or progesterone
      receptor positivity in the majority of cases of cystic nephroma is a novel
      finding.

PMID- 15578886
TI  - Frequent expression of human carcinoma-associated antigen, a mucin-type
      glycoprotein, in cells of prostatic carcinoma.
AB  - CONTEXT: Human carcinoma-associated antigen (HCA) is a mucin glycoprotein
      recognized by antibodies raised against epiglycanin, the latter having been
      originally purified from mouse mammary carcinoma cells. Human carcinoma
      associated antigen expression is increased in sera of patients with various
      carcinomas, including prostatic carcinoma. However, to our knowledge, expression
      of HCA in benign and neoplastic prostatic tissue has not been studied. OBJECTIVE:
      To compare the expression of HCA in cells of primary and metastatic prostatic
      carcinomas with its expression in non-carcinoma-associated cells. DESIGN: We
      studied 40 cases of primary and 36 cases of metastatic prostatic carcinomas by
      immunohistochemical staining with anti-HCA monoclonal antibodies G1 and HAE3. The
      blocks from primary carcinomas also contained normal prostatic tissue (40 cases),
      benign prostatic hyperplasia (16 cases), and high-grade prostatic intraepithelial
      neoplasia (32 cases). RESULTS: The 2 antibodies stained carcinomas more
      frequently than normal prostatic tissue, hyperplasia, and prostatic
      intraepithelial neoplasia (P < .001). The differences in the staining of low
      grade versus high-grade tumors was not statistically significant with either
      antibody. The staining was present in the cytoplasm and on the luminal membrane
      surface of the tumor cells and in the luminal secretions. In metastatic prostatic
      carcinomas, G1 and HAE3 staining was positive in 44% and 67% of the cases,
      respectively. CONCLUSIONS: Our results showed that mucin protein HCA is
      overexpressed in cells of prostatic carcinoma, which may have value in diagnosis
      and therapy. Its role in carcinogenesis also merits further study.

PMID- 15578887
TI  - Radiographically occult, diffuse intrasinusoidal hepatic metastases from primary
      breast carcinomas: a clinicopathologic study of 3 autopsy cases.
AB  - CONTEXT: Liver metastases usually present as radiographically detectable mass
      lesions that do not significantly compromise liver function. Rarely, metastatic
      carcinoma can diffusely infiltrate hepatic sinusoids, a pattern of metastasis
      that may be missed on imaging studies, and can result in liver failure.
      OBJECTIVE: To describe the clinicopathologic features of 3 cases of diffuse
      intrasinusoidal hepatic metastases from primary breast carcinomas identified at
      autopsy. DESIGN: Clinical histories and radiographic, macroscopic, and
      microscopic appearances of the livers were compared. Sampled liver tissue was
      stained with antibodies to E-cadherin, smooth muscle actin, and CD44. RESULTS:
      Two of 3 cases had a history of infiltrating ductal carcinoma of the breast and
      presented with new-onset liver failure, but no hepatic metastases were identified
      on radiologic imaging. An additional case had no history of carcinoma, presented
      with a severe thrombocytopenic thrombotic purpura-like syndrome, and metastatic
      carcinoma of the breast was diagnosed only at autopsy. The livers in all 3 cases
      at autopsy were homogeneous, firm, and tan-yellow, and contained no large
      metastatic lesions. Microscopically, poorly differentiated carcinoma diffusely
      infiltrated hepatic sinusoids. Antibodies to smooth muscle actin stained
      activated hepatic stellate cells lining involved sinusoids. Cell surface adhesion
      molecules, E-cadherin or CD44, were not detected in any hepatic metastases.
      CONCLUSION: Diffuse intrasinusoidal hepatic metastases of breast carcinoma can
      occupy a large percentage of the hepatic volume, yet remain occult both
      radiographically and macroscopically. This type of metastatic spread can present
      as cryptogenic liver failure. The 3 cases we studied were associated with an
      absence of E-cadherin and CD44 expression.

PMID- 15578888
TI  - Physician survey of a laboratory medicine interpretive service and evaluation of
      the influence of interpretations on laboratory test ordering.
AB  - CONTEXT: Complex coagulation test panels ordered by clinicians are typically
      reported to clinicians without a patient-specific interpretive paragraph.
      OBJECTIVES: To survey clinicians regarding pathologist-generated interpretations
      of complex laboratory testing panels and to assess the ability of the
      interpretations to educate test orderers. DESIGN: Surveys were conducted of
      physicians ordering complex coagulation laboratory testing that included
      narrative interpretation. Evaluation of order requisitions was performed to
      assess the interpretation's influence on ordering practices. SETTING: Physicians
      ordering coagulation testing at a large academic medical center hospital in
      Boston, Mass, and physicians from outside hospitals using the academic medical
      center as a reference laboratory for coagulation testing. OUTCOME MEASURES:
      Physician surveys and evaluation of laboratory requisition slips. RESULTS: In
      nearly 80% of responses, the ordering clinicians perceived that the interpretive
      comments saved them time and improved the diagnostic process. Moreover, the
      interpretations were perceived by ordering clinicians to help prevent a
      misdiagnosis or otherwise impact the differential diagnosis in approximately 70%
      of responses. In addition, interpretations appeared to be able to train the
      ordering clinicians as to the standard ordering practices. CONCLUSIONS: The
      results demonstrate physician satisfaction with an innovative information
      delivery approach that provides laboratory diagnostic interpretation and test
      ordering education to clinicians in the context of their daily workflow.

PMID- 15578889
TI  - Pulmonary and ophthalmic involvement with Erdheim-Chester disease: a case report
      and review of the literature.
AB  - Erdheim-Chester disease is a rare nonfamilial histiocytic disorder of unknown
      etiology with characteristic long bone findings. The 3-year survival rate for
      patients with Erdheim-Chester disease is 50%. Approximately 50% of patients have
      disease involvement in other tissues, including skin, retro-orbital and
      periorbital tissues, pituitary-hypothalamic axis, heart, kidney, retroperitoneum,
      breast, skeletal muscle, and sinonasal mucosa; about 20% of patients have lung
      involvement. Prognosis generally depends on the extent of the extraosseous
      disease. For patients with lung involvement, gender distribution is equal, but
      men typically present at an older age than do women. Approximately 80% of
      patients present with dyspnea, and most patients have diffuse interstitial
      infiltrates and pleural and/or interlobar septal thickening on chest radiology.
      Characteristic lung histopathology includes the accumulation of histiocytes with
      variable amounts of fibrosis and a variable lymphoplasmacytic infiltrate in a
      lymphangitic distribution. Immunostains are diagnostically useful, showing
      immunopositivity for CD68 and factor XIIIa and immunonegativity for CD1a. Birbeck
      granules are uniformly absent ultrastructurally.

PMID- 15578890
TI  - Idiopathic bilateral auricular ossificans: a case report and review of the
      literature.
AB  - Petrification of the auricle results in a rigid and immalleable ear. The etiology
      of such a finding is usually ectopic calcification. The condition has been
      associated with injurious processes, such as cold injury, and with various
      endocrinopathies, including Addison disease. In a significant number of cases,
      ossification occurs without knowledge of the precipitating cause or event. True
      auricular ossification is a rare occurrence, with only 12 histologically
      confirmed cases in the literature. We herein present the clinical and pathologic
      findings of another case. A 60-year-old man with diet-controlled diabetes
      presented with a 10-year history of slowly and insidiously stiffened auricles. He
      denied any precipitating historical events. Routine testing did not demonstrate
      systemic abnormalities. Radiographic examination revealed opacities consistent
      with bony structure in the auricles of the ears, with the right more prominent
      than the left. Histologic sampling demonstrated ossification with deposition of
      trabecular bone in proximity to normal elastic cartilage.

PMID- 15578891
TI  - Clear cell renal cell carcinoma with syncytial giant cells: a case report and
      review of the literature.
AB  - Renal cell carcinoma with syncytial giant cells (SGCs) is rare; to our knowledge,
      there are only 3 cases reported in the English literature. We report on a case
      that, unlike previous reports, was associated with higher grade renal cell
      carcinoma and an aggressive behavior. A 63-year-old man with gross hematuria was
      found to have a large left renal mass and no evidence of metastasis. The
      nephrectomy specimen contained a 14.8-cm mass that was confined within the renal
      capsule. Microscopically, a 1.8-cm area of SGCs was noted in a background of
      clear cell renal cell carcinoma of Fuhrman nuclear grades 2 to 4. The SGCs had
      voluminous cytoplasm, multiple large nuclei with prominent nucleoli, and focal
      emperipolesis. Identical to the background mononuclear tumor cells, the SGCs were
      positive for AE1/AE3, vimentin, and epithelial membrane antigen and negative for
      CD68, beta-human chorionic gonadotropin, and mucin. Three months after surgery,
      the patient developed metastases in the liver, right kidney, and lungs.

PMID- 15578892
TI  - Multiple cavernous hemangiomas of the lung: a case report and review of the
      literature.
AB  - Cavernous hemangiomas are benign vascular tumors most commonly seen in the head
      and neck region in childhood. They have been described rarely in the lungs. We
      describe a patient with incidental pulmonary nodules discovered at autopsy, which
      measured up to 0.9 cm and which were present in the lung parenchyma, as well as
      on the pleura. The nodules were composed of dilated vascular spaces lined by
      flattened bland cells. Immunohistochemical studies of the lining cells revealed
      CD34 and factor VIII immunoreactivity, consistent with a lesion of endothelial
      origin. Taken together, the gross, microscopic, and immunohistochemical findings
      support the diagnosis of multiple pulmonary cavernous hemangiomas.

PMID- 15578893
TI  - Gastrointestinal stromal tumor presenting as a recurrent vaginal mass.
AB  - Gastrointestinal stromal tumors are CD117 (c-Kit)-positive mesenchymal neoplasms
      with histologic and ultrastructural features of the interstitial cell of Cajal.
      While tumors outside of the gastrointestinal tract have been described, to our
      knowledge the case we present is the first such case in the vagina. We describe a
      75-year-old woman with a recurrent vaginal gastrointestinal stromal tumor without
      apparent rectal involvement. This tumor was characterized by short intersecting
      fascicles of spindled cells, focal necrosis, and 12 to 15 mitoses per 50 high
      power fields. Immunohistochemistry revealed diffuse cytoplasmic positivity for
      CD117 (c-Kit), CD34, vimentin, and h-caldesmon. Tumor cells were negative for
      S100, desmin, actin, and CAM 5.2. The differential diagnosis in this case
      included a vaginal smooth muscle tumor. While histologically similar to a smooth
      muscle neoplasm, the immunohistochemical profile ruled out smooth muscle
      differentiation. Gastrointestinal stromal tumor should be considered in the
      differential diagnosis of vaginal mesenchymal neoplasms.

PMID- 15578894
TI  - Leukemoid reaction: a diagnostic clue in metastatic carcinoma mimicking classic
      Hodgkin lymphoma.
AB  - We report on 2 patients who were initially suspected to have classic Hodgkin
      lymphoma because of lymphadenopathy and the presence of Reed-Sternberg-like
      cells. Both patients had an associated leukemoid reaction (using a threshold
      leukocyte count of 50 000/microL) and were eventually diagnosed with metastatic
      carcinoma. Disseminated carcinoma can mimic Hodgkin lymphoma clinically,
      radiologically, and histologically. Reed-Sternberg-like cells may be found in
      carcinomas, and they represent a particularly challenging diagnostic pitfall for
      the unwary. When these cells lead to a suspicion of Hodgkin lymphoma, the
      presence of a leukemoid reaction should prompt the pathologist to question the
      diagnosis. Misdiagnosis can be avoided by the use of cytokeratin whenever a
      leukemoid reaction is present in a suspected case of Hodgkin lymphoma.

PMID- 15578895
TI  - Pathologic quiz case: infratentorial tumor in a middle-aged woman. Oncocytic
      variant of choroid plexus papilloma.

PMID- 15578896
TI  - Pathologic quiz case: a 56-year-old woman with anterior nasal pain and
      intermittent epistaxis. Alternaria alternate infection of the nasal sinus.

PMID- 15578897
TI  - Pathologic quiz case: an anterior neck mass in a 5-month-old female infant.
      Wattle (congenital cervical tragus).

PMID- 15578898
TI  - Pathologic quiz case: soft tissue calcifications of the shoulder in a 31-year-old
      woman. Synovial chondromatosis.

PMID- 15578899
TI  - Physaliphorous cells in chordoma.

PMID- 15578900
TI  - Burkitt leukemia.

PMID- 15578901
TI  - Helicobacter heilmannii infection in a child.

PMID- 15578902
TI  - Polyomavirus in a lung transplant patient.

PMID- 15578903
TI  - Low-grade neuroendocrine carcinoma (carcinoid tumor) of the prostate.
AB  - A case of primary, prostatic, low-grade neuroendocrine carcinoma (carcinoid
      tumor) is described. The patient is an 86-year-old man who presented with
      symptoms of gross hematuria of several days' duration. Physical examination and a
      bladder biopsy specimen revealed the presence of a primary adenocarcinoma of the
      bladder with invasion into the muscularis propria. A cystoprostatectomy was
      performed, which revealed the presence of invasive adenocarcinoma of the bladder.
      Prostatic sampling demonstrated the presence of a low-grade neuroendocrine
      carcinoma (carcinoid tumor) and a small focus of well-differentiated conventional
      adenocarcinoma. Immunohistochemical studies using neuroendocrine markers clearly
      demarcated the presence of the neuroendocrine tumor. The case presented herein
      highlights the ubiquitous distribution of neuroendocrine neoplasms along the male
      genitourinary tract and the presence of 3 separate neoplasms in the genitourinary
      tract.

PMID- 15578904
TI  - Solitary fibrous tumor of the auditory canal.
AB  - Solitary fibrous tumor (SFT) is an uncommon spindle cell neoplasm of increasing
      incidence that was originally described to be of pleural origin; however, more
      recently, SFT has been reported in extrapleural sites, including the orbit,
      liver, salivary glands, tongue, nose, paranasal sinuses, larynx, retroperitoneum,
      meninges, and thyroid. The increase in the number of SFTs does not necessarily
      mean increased incidence of this tumor but rather an increased understanding of
      this tumor, especially recognition of this tumor in extrapleural locations, which
      has been aided by immunohistochemical analysis. We report a case of SFT in the
      auditory canal, which to our knowledge has not been previously reported, as
      evident by morphologic findings and immunophenotype.

PMID- 15578905
TI  - Pathologic quiz case: a 60-year-old woman with diffuse uterine enlargement.
      Primary osteosarcoma of the uterus.

PMID- 15578906
TI  - Pathologic quiz case: an 87-year-old woman with a mass in the tail of the
      pancreas. Pancreatic lymphangioma with "ovarian-like" stroma.

PMID- 15578907
TI  - Pathologic quiz case: a 56-year-old man with bilateral renal masses. Bilateral
      renal oncocytosis.

PMID- 15578908
TI  - Pathologic quiz case: a 30-year-old man with lower abdominal and back pain.
      Anaplastic large cell lymphoma (Ki-1 lymphoma) of the pancreas.

PMID- 15578909
TI  - Pathologic quiz case: a 64-year-old man with hematuria, intracranial hemorrhage,
      and severe coagulation abnormalities. Long-acting warfarin-like rodenticide
      toxicity.

PMID- 15578910
TI  - Pathologic quiz case: multiple liver and lung nodules. Epithelioid
      hemangioendothelioma of the liver.

PMID- 15578912
TI  - Extracellular tropomyosin: a novel common pathway target for anti-angiogenic
      therapy.
AB  - Angiogenesis is characterized by the development of new vasculature from pre
      existing vessels and plays a central role in physiological processes such as
      embryogenesis, wound healing and female reproductive function, as well as
      pathophysiologic events including cancer, rheumatoid arthritis and diabetic
      retinopathy. The growth and metastasis of tumors is critically dependent upon
      angiogenesis. Although targeting angiogenesis as a therapeutic strategy has to
      date met with limited success in the clinic, the recent FDA approval of the anti
      VEGF antibody Avastin has validated the use of anti-angiogenic therapeutic
      strategies for cancer treatment. We have recently identified several plasma
      proteins having anti-angiogenic properties, including Histidine-Proline-Rich
      Glycoprotein (HPRG) and activated high-molecular-weight kininogen (HKa). Both of
      these proteins are able to induce apoptosis in endothelial cells in vitro and can
      inhibit angiogenesis in vivo. Recent studies from our laboratories have also
      identified a novel cell-surface binding protein for HKa that mediates its anti
      angiogenic activity. This protein, tropomyosin, is normally found inside the cell
      and is associated with the actin cytoskeleton, where it plays a critical role in
      stabilizing actin filaments in a variety of cell types. However, in angiogenic
      endothelial cells, tropomyosin appears to have extracellular localization.
      Previous studies have also suggested the involvement of tropomyosin in the anti
      angiogenic activity of endostatin, and our recent work indicates that tropomyosin
      may mediate the antiangiogenic activity of HPRG as well. In this review, we
      summarize data describing extracellular tropomyosin as a novel receptor for
      multiple anti-angiogenic proteins. Extracellular tropomyosin may therefore
      represent a previously undescribed central target for the development of anti
      angiogenic therapy.

PMID- 15578913
TI  - Angiotensin-I converting enzyme inhibitors as potential anti-angiogenic agents
      for cancer therapy.
AB  - Angiotensin-I converting enzyme inhibitors (ACE-Is) are commonly used as safe
      antihypertensive agents, and it has recently been suggested that they decrease
      the risk of cancer development. Recent studies have revealed that the renin
      angiotensin system (RAS) is involved in the development of many types of tumor.
      Angiotensin-II (AT-II) has many biological effects, including neo
      vascularization, which plays a pivotal role in tumor development. AT-II induces a
      potent angiogenic factor, namely the vascular endothelial growth factor (VEGF).
      Some studies have proven that several ACE-Is are potent inhibitors of
      experimental tumor development and angiogenesis at clinically comparable doses.
      VEGF expression in tumors is also significantly suppressed by ACE-Is. When used
      in combination with the conventional anti-cancer drugs, ACE-Is exert more potent
      anti-tumor activities as compared with either single agent, in addition to
      suppression of the intra-tumoral angiogenesis. Furthermore, ACE-Is reportedly not
      only suppress tumor growth but also attenuate the carcinogenesis process in which
      angiogenesis is involved. Since ACE-Is are already in widespread clinical case
      without any serious adverse effects, they may represent a potential new strategy
      for cancer therapy and chemoprevention.

PMID- 15578914
TI  - Targeting apoptosis pathways in cancer therapy.
AB  - Killing of tumor cells by anticancer therapies commonly used in the treatment of
      cancer, e.g. chemotherapy, gamma-irradiation, immunotherapy or suicide gene
      therapy, is predominantly mediated by triggering apoptosis, the cell's intrinsic
      death program. Accordingly, defects in apoptosis pathways can result in cancer
      resistance to current treatment approaches. Understanding the molecular
      mechanisms that regulate cell death programs including apoptosis, and how
      resistant forms of cancer evade apoptotic events, may provide novel opportunities
      for cancer drug development.

PMID- 15578915
TI  - Chemotherapeutic agents that induce mitochondrial apoptosis.
AB  - In cancer chemotherapy, it is necessary to design an agent that suppresses or
      inhibits the targets that influence cell growth and apoptosis. We focus on the
      apoptotic pathway via mitochondria in this article. In this pathway, c-Jun N
      terminal kinase (JNK), one of the stress activated protein kinases, is
      predominantly activated by apoptotic stimuli. JNK activity is inhibited by the
      binding of glutathione S-transferase P1-1 (GST P1-1) through protein-protein
      interactions. It has been noted that GST P1-1 overexpression plays an important
      role in carcinogenesis and in part in the MDR phenotype. We show several useful
      modifications of an anticancer agent that suppress the enzyme activity and
      expression of GST P1-1. The release of cytochrome c from mitochondria to the
      cytosol during apoptosis is mediated by the mitochondrial permeability transition
      pore, which is a protein complex formed by the voltage-dependent anion channel,
      members of the pro- and anti- apoptotic Bax-Bcl-2 protein family, cyclophilin D,
      and adenine nucleotide (ADP/ATP) translocators. We propose some drugs, including
      a proteasome inhibitor that can triger the permeability transition.

PMID- 15578916
TI  - Proline-directed protein kinase FA as a potential target for diagnosis and
      therapy of human cancers.
AB  - Proline-directed protein kinase FA (PDPK FA) was originally identified as a
      phosphatase activating factor (FA) but has subsequently been characterized as a
      multisubstrate/multifunctional PDPK possibly associated with human cancers. In
      recent years, the immunohistochemical study revealed that PDPK FA was highly
      expressed in tumor mass and preferentially overexpressed in the invasive lesions
      of the resected tissue sections obtained from various types of cancer patients.
      The clinicopathologic study further revealed a close correlation of the
      overexpression of PDPK FA with poor prognosis of the cancer patients. The
      antisense gene therapy study also confirmed that due to its
      multisubstrate/multifunctional PDPK nature, the overexpression of PDPK FA is
      essential for the development of malignant growth, tumorigenesis, invasion,
      metastasis, anti-differentiation, anti-apoptosis and chemoresistance in human
      cancers. From immunohistochemical, clinicopathologic and antisense gene
      therapeutic studies combined together, PDPK FA has emerged as a key regulator of
      all aspects of neoplasia. In this way, nature provides prima facie evidence of a
      particular protein kinase's pivotal importance to the neoplastic state. PDPK FA
      therefore represents a newly-described, previously-undiscovered novel signal
      transducing target for diagnosis, disease monitoring, drug screening and therapy
      of human cancers.

PMID- 15578917
TI  - Alphaviruses and their derived vectors as anti-tumor agents.
AB  - The alphaviruses Semliki Forest virus (SFV) and Sindbis virus have recently been
      developed as prototype anti-cancer agents. These are RNA-containing enveloped
      viruses that code for only 9 proteins of unique sequence. The standard
      recombinant SFV vector system consists of suicide particles containing
      recombinant RNA. In addition, alphavirus vectors capable of limited
      multiplication in the host are also being developed. Several strategies are being
      adopted to construct prototype SFV vectors for cancer treatment. These include:
      1) construction of both prophylactic and therapeutic vaccines to stimulate
      immunity to tumor-associated antigens, 2) use of apoptosis induction to destroy
      tumor cells, which includes both the use of the inherent apoptosis-inducing
      ability of the vector and the action of pro-apoptotic genes cloned into the
      vector, and 3) expression of cytokines and other immunoregulatory proteins by the
      vector that enhance anti-tumor immune responses and/or inhibit tumor cell growth.
      This includes the use of cytokines such as IL-12 that target angiogenesis.
      Sindbis virus appears to have a natural tropism for tumor cells that may allow
      targeting both of the wild-type virus and the vector. This approach may also be
      useful for targeting metastases. For SFV, neurovirulence and/or neurotropism, as
      well as other tissue damage, may preclude the use of unmodified replication
      competent wild-type virus in tumor treatment. However, it may be possible to use
      such a virus in animals that have been vaccinated, using a vector-derived
      vaccine.

PMID- 15578918
TI  - The life cycle of cutaneous T cell lymphoma reveals opportunities for targeted
      drug therapy.
AB  - The diverse clinical presentations of cutaneous T cell lymphoma (CTCL) have been
      unified by immunologic characterization of the malignant T cells as an expansion
      of clonal, CD4+ inducer T cells with affinity for epidermal association with
      Langerhans cells (LC), an immature member of the dendritic cell (DC) family.
      Features of the life cycle of CTCL have recently been elucidated through
      development of an in vitro cell culture system. In this system, the proliferation
      and survival of the CTCL cells is tied to an association with immature monocyte
      derived DC. Growth of the CTCL cells requires direct contact with the DC and both
      cell types survive in the presence of supportive cytokines for 3 months.
      Separation of the CTCL cells and the DC, or DC maturation truncates the synergy
      between the two cell populations and results in rapid death of both cell types.
      The CTCL cells perpetuate DC immaturity and survival through secretion of
      interleukin 10 (IL10) and transforming growth factor-beta (TGF-beta). The
      immature DC are aggressively phagocytic and can engulf apoptotic CTCL cells that
      have exhausted their proliferative potential and present peptides derived from
      the apoptotic material in class II MHC molecules to the T cell receptor (TCR) of
      the CD4+ CTCL cell. CTCL cells are induced to become T-regulatory (Treg) cells
      when their TCR is triggered by DC class II presentation of peptides derived from
      apoptotic material. Treg CTCL cells suppress immune responses and secrete IL10
      and TGF-beta, cytokines that perpetuate DC immaturity, providing continued
      opportunity for DC stimulation of CTCL cell growth. Understanding the CTCL cell
      life cycle unveils a variety of potential targets that can be exploited for
      therapeutic intervention.

PMID- 15578919
TI  - Mammalian target of rapamycin (mTOR) inhibitors as anti-cancer agents.
AB  - Highly specific signal transduction inhibitors are being developed as anti-cancer
      agents against an array of molecular targets, with the promise of increased
      selectivity and lower toxicity than classic cytotoxic chemotherapy agents.
      Rapamycin and its analogues are a promising class of novel therapeutics that
      specifically inhibit signaling from the serine-threonine kinase, mammalian target
      of rapamycin (mTOR). mTOR is a key intermediary in multiple mitogenic signaling
      pathways and plays a central role in modulating proliferation and angiogenesis in
      normal tissues and neoplastic processes. Rapamycin potently inhibits T-cell
      proliferation, and is approved for clinical use as an immuno-suppressant
      following kidney transplantation. Hyperactivation of mTOR signaling has been
      implicated in tumorigenesis, and promising pre-clinical studies in several tumor
      types suggest that the anti-proliferative and anti-angiogenic properties of
      rapamycin may be useful in cancer therapy. These studies have led to several
      clinical trials evaluating the safety and efficacy of rapamycin analogs in cancer
      therapy. The goal of this article is to review the mechanism of action of
      rapamycin as an anti-cancer agent, and to review the clinical experience with
      rapamycin and rapamycin analogs as immunosuppressive and anti-neoplastic
      therapeutic agents.

PMID- 15578920
TI  - Targeting the STAT pathway in head and neck cancer: recent advances and future
      prospects.
AB  - Head and neck cancer, the sixth most common type of cancer worldwide, is
      associated with a dismal prognosis that has minimally improved during the last
      few decades. Future advances in the treatment and prognosis of this fatal disease
      largely rely upon a better understanding of the molecular events that underlie
      tumor development and progression, allowing specific targeting of the involved
      molecules and pathways. In this context, recent efforts have revolved around a
      family of transcription factors known as STATs (signal transducers and activators
      of transcription). STAT proteins comprise a family of latent cytoplasmic
      transcription factors that become transiently activated in response to
      extracellular signals, leading to regulation of diverse physiological responses.
      There is compelling evidence that persistent activation of specific STAT
      molecules, especially Stat3 and Stat5, possesses oncogenic properties in a number
      of human cancers, including head and neck cancer. The presence of constitutively
      activated STAT molecules in cancer cells is mainly attributed to the
      dysregulation of upstream activating pathways and the aberration of negative
      regulatory mechanisms. The end result is induction of specific target genes that
      stimulate cell proliferation, prevent apoptosis, promote angiogenesis and
      facilitate tumor immune evasion. Therefore, targeting and disruption of oncogenic
      STAT signaling may theoretically be accomplished through various approaches,
      involving direct (e.g. interference with the various facets of STAT expression,
      activation or function) and indirect strategies (e.g. inhibition of upstream
      signaling events and enhancement or restoration of negative regulatory
      mechanisms). The availability of multiple potential targets for interruption of
      aberrant STAT signaling in cancer and the thus-far promising results have
      generated optimism for the clinical applicability of STAT targeting in head and
      neck cancer, which is the focus of this review.

PMID- 15578921
TI  - Wnt/beta-catenin signaling pathway as a novel cancer drug target.
AB  - Wnt proteins are a large family of secreted glycoproteins. Wnt proteins bind to
      the Frizzled receptors and LRP5/6 co-receptors, and through stabilizing the
      critical mediator beta-catenin, initiate a complex signaling cascade that plays
      an important role in regulating cell proliferation and differentiation.
      Deregulation of the canonical Wnt/beta-catenin signaling pathway, mostly by
      inactivating mutations of the APC tumor suppressor, or oncogenic mutations of
      beta-catenin, has been implicated in colorectal tumorigenesis. Although oncogenic
      mutations of beta-catenin have only been discovered in a small fraction of non
      colon cancers, elevated levels of beta-catenin protein, a hallmark of activated
      canonical Wnt pathway, have been observed in most common forms of human
      malignancies, indicating that activation of this pathway may play an important
      role in tumor development. Over the past 15 years, our understanding of this
      signaling pathway has significantly improved with the identification of key
      regulatory proteins and the important downstream targets of beta-catenin/Tcf
      transactivation complex. Given the fact that Wnt/beta-catenin signaling is
      tightly regulated at multiple cellular levels, the pathway itself offers ample
      targeting nodal points for cancer drug development. In this review, we discuss
      some of the strategies that are being used or can be explored to target key
      components of the Wnt/beta-catenin signaling pathway in rational cancer drug
      discovery.

PMID- 15578922
TI  - Surface antigens/receptors for targeted cancer treatment: the GnRH
      receptor/binding site for targeted adenocarcinoma therapy.
AB  - Colon, breast and lung adenocarcinomas - three of the major malignancies
      occurring in humans, together with ovarian, endometrial, kidney and liver
      adenocarcinomas, account for more then 50% of cancer-related death. As the number
      of cancer-related deaths has not decreased in recent years, major efforts are
      being made to find new and more specific drugs for cancer treatment. One of the
      approaches developed in recent years for targeted cancer therapy is the
      construction and use of chimeric proteins. Chimeric cytotoxins are a class of
      targeted molecules designed to recognize and specifically destroy cells over
      expressing specific receptors. These molecules, designed and constructed by gene
      fusion techniques, comprise both the cell-targeting and the cell-killing
      moieties. Our laboratory has developed a number of chimeric proteins based on an
      analog of Gonadotropin Releasing Hormone (GnRH) as their targeting moiety. These
      chimeras recognize a GnRH-binding site that, we found, was over-expressed on a
      surprisingly wide variety of cancers, all confined to the adenocarcinoma type. A
      GnRH analog was fused to a large number of killing moieties, including bacterial
      or human pro-apoptotic proteins. All GnRH-based chimeric proteins selectively
      killed adenocarcinoma cells both in vitro and in vivo. Utilizing GnRH-based
      chimeric proteins for targeted therapy could open up new vistas in the fight
      against adenocarcinomas in humans. This review summarizes the latest developments
      in the area of targeted cancer therapy via specific antigens/receptors, as well
      as our latest findings in targeting GnRH-binding sites using GnRH-based chimeric
      proteins for specific and targeted adenocarcinoma therapy in humans.

PMID- 15578923
TI  - Bacteria and bacterial toxins as therapeutic agents for solid tumors.
AB  - Patients with advanced solid tumors frequently relapse and succumb to their
      metastatic disease after developing resistance to conventional treatment
      modalities such as chemotherapy and radiotherapy. In these patients, novel
      strategies of targeting widespread tumors are urgently needed. The increasing
      knowledge of the underlying pathogenetic mechanisms has led to the identification
      of numerous molecules that are overexpressed in various tumors and accumulate at
      the cell surface. The use of genetically modified bacteria and their toxins
      targeting these surface molecules has emerged as a promising new treatment
      strategy in refractory cancers. This review focuses on bacterial toxins such as
      Diphtheria toxin (DT), Pseudomonas exotoxin A (PE) and Clostridium perfringens
      enterotoxin (CPE). In addition, the use of anaerobic bacteria such as
      Clostridium, Salmonella and Bifidobacterium spp. as drug-delivery systems
      targeting hypoxic tumor areas will be discussed as a new therapeutic modality of
      advanced solid tumors.

PMID- 15578924
TI  - Quality, not quantity: the role of natural products and chemical proteomics in
      modern drug discovery.
AB  - Chemical genetics and reverse chemical genetics parallel classical genetics but
      target genes at the protein level and have proven useful in recent years for
      screening combinatorial libraries for compounds of biological interest. However,
      the performance of combinatorial chemistry in filling pharmaceutical pipelines
      has been lower than anticipated and the tide may be turning back to Nature in the
      search for new drug candidates. Even though diversity oriented synthesis is now
      producing molecules that are natural product-like in terms of size and
      complexity, these molecules have not evolved to interact with biomolecules.
      Natural products, on the other hand, have evolved to interact with biomolecules,
      which is why so many can be found in pharmacopoeias. However, the cellular
      targets and modes of action of these fascinating compounds are seldom known,
      hindering the drug development process. This review focuses on the emergence of
      chemical proteomics and reverse chemical proteomics as tools for the discovery of
      cellular receptors for natural products, thereby generating protein/ligand pairs
      that will prove useful in identifying new drug targets and new biologically
      active small molecule scaffolds. Such a system-wide approach to identifying new
      drugable targets and their small molecule ligands will help unblock the
      pharmaceutical product pipelines by speeding the process of target and lead
      identification.

PMID- 15578925
TI  - Current progress in natural product-like libraries for discovery screening.
AB  - Natural product-like libraries represent an effort to combine the attractive
      features of natural products and combinatorial libraries for high-throughput
      screening. Three approaches to natural product-like library design are discussed:
      (1) Libraries based on core scaffolds from individual natural products, (2)
      libraries of diverse structures with general structural characteristics of
      natural products, and (3) libraries of diverse structures based on specific
      structural motifs from classes of natural products. Examples of successful
      applications in discovery screening are described for each category. These
      studies highlight the exciting potential of natural product-like libraries in
      both chemical biology and drug discovery.

PMID- 15578926
TI  - Forward chemical genetics: library scaffold design.
AB  - With the unraveling of the entire human genome, it has become imperative to
      understand the function of the gene products, proteins. Within the past several
      years, chemical genetics has gained recognition as a powerful approach to study
      protein function by using small molecules as gene knock-out or knock-in mimics.
      Forward chemical genetics is a three-step process; the design and synthesis of a
      small molecule library represents the first step followed secondly by the search
      for novel phenotypes and then by isolation and identification of target
      protein(s). This review will focus on the first step, the design of the scaffold
      for small molecule libraries. It will also examine the connection between the
      choice of a scaffold and the propensity of that library to demonstrate enhanced
      biological activity when tested in certain cellular systems.

PMID- 15578927
TI  - Synthetic molecules that modulate transcription and differentiation: hints for
      future drug discovery.
AB  - Regulation of gene transcription and cell differentiation often induces drastic
      phenotypes in living organisms. External, precise control over these processes
      through small organic molecules represents a challenge in chemistry and biology.
      Our laboratory has been discovering small organic molecules that modulate
      transcription or differentiation and using them as a tool to understand
      biological phenomena. This personal perspective summarizes our contributions to
      chemical biology and chemical genetics in the fields of gene transcription and
      cell differentiation. Our case studies may foreshadow the promise and the
      challenge of future drug discovery.

PMID- 15578928
TI  - Identification and characterization of Sir2 inhibitors through phenotypic assays
      in yeast.
AB  - Yeast Sir2 is a defining member of a large family of protein deacetylases found
      in organisms ranging from bacteria to humans. SIR2 was discovered as a gene
      required for mating in S. cerevisiae 25 years ago, but it was only recently that
      Sir2's activity as an NAD-dependent protein deacetylase was established. However,
      years of extensive research did generate a large body of knowledge about the
      cellular roles of Sir2 in yeast long before its biochemical function was
      discovered. In addition to Sir2, yeast have four additional NAD-dependent histone
      deacetylases Hst1-4 (for homologue of Sir2), with distinct cellular roles.
      Detailed knowledge of the phenotypes of SIR2 and HST loss of function mutants has
      allowed design of a series of cell based screens that yielded the first
      inhibitors of NAD-dependent protein deacetylases. These phenotypic assays,
      amenable to high throughput screening, and coupled with transcript array analysis
      for evaluation of compound specificity, allowed the identification and detailed
      characterization of a series of Sir2 inhibitors, entirely bypassing traditional
      biochemical approaches.

PMID- 15578929
TI  - Mapping chemical space using molecular descriptors and chemical genetics:
      deacetylase inhibitors.
AB  - An objective of chemical genetics is to understand the relationships between the
      structures of small molecules and their phenotypic effects in intact living
      systems. We present here the results of a global analysis of a molecular
      descriptor space constructed using structural descriptors of an aryl 1,3-dioxane
      based diversity-oriented synthesis-derived library containing structural biasing
      elements directed at inhibiting protein deacetylases. Using principal component
      analysis and three-dimensional visualization, we generated metric space maps with
      morphological features contributed by different diversity elements within the
      library. Filtering these maps using phenotypic descriptors derived from
      measurements of small-molecule activities in an array of cell-based assays
      revealed different densities of biological activity within specific subspaces.
      These results provide evidence that certain structural features may be important
      for conferring potency and selectivity on deacetylase inhibitors with respect to
      tubulin and histone acetylation. Moreover, these results highlight an example of
      the importance of using functional measures to assess molecular diversity.
      Similar analyses of other chemical spaces and activity classes promise to
      facilitate the development of chemical genetics.

PMID- 15578930
TI  - Target identification strategies in chemical genetics.
AB  - Chemical inhibitors have had a profound impact on many diverse fields of biology.
      The goal of chemical genetics is to use small molecules to perturb biological
      systems in a manner conceptually similar to traditional genetics. Key to the
      advancement of the chemical genetic paradigm is the further development of tools
      and approaches for the identification of the protein targets of active compounds
      identified in chemical genetic screens. This review will address historic
      examples in which forward chemical genetics yielded new insight into a biological
      problem through successful identification of the target of an active molecule.
      The approaches covered have been grouped into two broad classes: target
      identification by affinity-based methods and target identification by deduction.
      Strengths and shortcomings of each approach as it pertains to their application
      to modern chemical genetics will be discussed. Finally, a series of new genomic
      and proteomic-based techniques for target identification will be described.
      Although a truly general approach to target identification has yet to be
      developed, these examples illustrate that there are many effective strategies for
      successfully elucidating the biological targets of active small molecules.

PMID- 15578931
TI  - Targeted degradation of proteins by small molecules: a novel tool for functional
      proteomics.
AB  - A novel strategy that targets protein for degradation has recently been developed
      by exploiting a protein-targeting chimeric molecule ('Protac'). Typically, the
      chimeric Protac is composed of a small-molecule ligand ('bait') on one end and a
      synthetic octapeptide on the other. This octapeptide is recognized by E3
      ubiquitin ligase pVHL (von Hippel Lindau tumor suppressor protein), thereby
      recruiting a small molecule-bound protein ('prey') to pVHL for ubiquitination and
      degradation. Since selective degradation of a cellular protein generates a "loss
      of function" mutation, this protein knock-out strategy may be useful to study the
      function of a given protein or to evaluate whether a cellular protein is a
      potential target for drug intervention, in a manner reminiscent of gene knock-out
      or siRNA approaches. Herein, we show that a synthetic pentapeptide is sufficient
      to interact with pVHL E3 ligase, and that the pentapeptide-based Protac
      efficiently induces ubiquitination and degradation of target protein. Our results
      also demonstrate that the pentapeptide-based Protac can enter cells efficiently
      to exerts its biological activity effectively. These results suggest that the
      synthetic pentapeptide can be used either directly in the preparation of cell
      permeable Protacs or as a template to develop peptidomimetic or non-peptide
      Protacs.

PMID- 15578932
TI  - Photo-affinity labeling strategies in identifying the protein ligands of
      bioactive small molecules: examples of targeted synthesis of drug analog
      photoprobes.
AB  - The discovery of many new targets by chemical genetics has frequently exploited
      the fact that their biologically active chemical ligands were reactive and thus
      could covalently bind to their protein target(s). When experimental compounds or
      therapeutic agents with unidentified mechanisms of action do not contain reactive
      groups that can covalently label the putative site of molecular action, it may be
      possible to create a reactive photo-affinity probe if there is sufficient
      knowledge of the structure-activity relationship of the chemical series. Two
      specific examples are presented. These include the use of photo-affinity probes
      in the identification of the mechanism of action of synthetic oxazolidinones, a
      class of novel acting antibiotics and in the identification of a novel target for
      the insulin-sensitizing thiazolidinediones. Developments in photo-affinity
      labeling and combinatorial library design now imply that the parallel
      incorporation of photo-probes into screening library design could, at least in
      principle, greatly facilitate reverse pharmacological and chemical genetics
      approaches to protein target discovery.

PMID- 15578933
TI  - High throughput screening of genetic polymorphisms by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry.
AB  - In the post genomic era, the screening of many different genetic polymorphisms in
      large populations represents a major goal that will facilitate the understanding
      of individual genetic variability in the development of multi factor diseases and
      in drug response and toxicities. The increasing interest in these pathogenetic
      and pharmacogenomic studies by both academic and pharmaceutical industry
      researchers has increased the demand for broad genome association studies. This
      demand has produced a boom in the development of new and robust high throughput
      screening methods for genotype analysis. Matrix-assisted laser-desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents an emerging
      and powerful technique for DNA analysis because of its high speed, accuracy, no
      label requirement, and cost-effectiveness. So far, many MALDI-TOF MS approaches
      have been developed for rapid screening of single nucleotide polymorphisms
      (SNPs), variable sequences repeat, epigenotype analysis, quantitative allele
      studies, and for the discovery of new genetic polymorphisms. The more established
      methods are based on single base primer extension and minisequencing implemented
      with new chemical features to overcome the limitations associated with DNA
      analysis using MALDI-TOF MS. These new promising methods of genotyping include
      both photochemical and other different chemical and enzyme cleavage strategies
      that facilitate sample automation and MS analysis for both real-time genotyping
      and resequencing screening. In this review, we analyze and discuss in depth the
      advantages and the limitations of the more recent developments in MALDI-TOF MS
      analysis for large-scale genomic studies applications.

PMID- 15578934
TI  - Multiplexed RT- PCR for high throughput screening applications.
AB  - To increase efficiency of high throughput gene expression profiling, we
      established a new TaqMan RT-PCR (real-time reverse transcriptase-polymerase chain
      reaction with internal probes for the quantification of PCR products) method for
      quantitative mRNA expression analysis. In this procedure, we utilized poly-A mRNA
      capture plates and validated a multiplexed single tube RT-PCR assay for cell
      culture applications, including compound testing via gene induction measurement.
      In the described procedure, all steps including RNA extraction, RT and PCR are
      performed in the same tube, thus significantly enhancing throughput of this
      method. Optimization of conditions, including the number of cells necessary for
      detection of mRNA signal was performed. With a relatively abundant message such
      as GAPDH, we saw a linear response for all of the concentrations tested, from
      10,000 cells to 10 cells. We have also demonstrated multiplexing of different
      targets within the PCR reactions. In these experiments, we combined VIC-labeled
      probes for GAPDH with several FAM-labeled probes obtained from Assays On Demand
      (Applied Biosystems). In the reported experiments, multiplexing did not affect
      the efficiency of RT-PCR. We also demonstrated the utility of this technology for
      compound screening applications. The described technology also has the potential
      to accelerate studies on target and biomarker identification and toxicity
      assessment in ADMET (absorption, distribution, metabolism, elimination, and
      toxicity) testing.

PMID- 15578935
TI  - Anti-endotoxin agents. 2. Pilot high-throughput screening for novel
      lipopolysaccharide-recognizing motifs in small molecules.
AB  - Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are an integral part of
      the outer leaflet of the outer-membrane of Gram-negative bacteria.
      Lipopolysaccharides play a pivotal role in the pathogenesis of 'Septic Shock', a
      major cause of mortality in the critically ill patient, worldwide. The
      sequestration of circulatory endotoxin may be a viable therapeutic strategy for
      the prophylaxis and treatment of Gram-negative sepsis. We have earlier shown that
      the pharmacophore necessary for small molecules to bind LPS is simple, comprising
      of two protonatable cationic functions separated by about 15 A, permitting the
      simultaneous interaction with the negatively charged phosphates on lipid A, the
      toxically active center of endotoxin. In this report, we employ high-throughput
      screening methods, using a novel fluorescent probe displacement method. Searches
      in three-dimensional structure databases yielded about approximately 4000
      commercially available small molecules, each possessing two cationic functions
      spaced approximately 15 A apart. Approximately 400 such compounds have been
      screened in an effort to validate the method by which high-affinity endotoxin
      binders can be identified. We show that the IC50 values that are obtained from
      the fluorescence-based primary screen are correlated both to the enthalpy of
      binding, as measured by isothermal titration calorimetry, as well as to
      biological potency in vitro assays. By performing rapid toxicity screens in
      tandem with the bioassays, lead compounds of interest can be easily identified
      for further systematic structural modifications and SAR studies.

PMID- 15578936
TI  - High throughput screening of beta-amyloid secretion inhibitors using homogenous
      time-resolved fluorescence.
AB  - A cell-based assay using homogeneous time-resolved fluorescence has been
      developed for high throughput screening of putative beta-amyloid
      (Abeta)production inhibitors. In this assay, total Abeta is detected by simply
      adding two commercially available antibody complexes. The first was a
      biotinylated monoclonal antibody (4G8), specifically recognizing an epitope
      comprising the residues 17-24 of the Abetapeptide, complexed with europium
      cryptate-streptavidin conjugate. The second was a polyclonal antibody (BioS-N),
      raised against the N-terminus of the Abeta peptide, complexed with an
      allophycocyanin-anti rabbit antibody conjugate. Binding of the two complexes to
      the Abeta peptide brought europium cryptate (fluorescence donor) and
      allophycocyanin (fluorescence acceptor) into close proximity, consequently a
      fluorescent resonance energy transfer signal was produced upon excitation at 337
      nm. The resulting fluorescence signal (665 nm) was then detected using a
      Discovery or a ViewLux reader. Detection of Abeta by the proposed method is
      possible at concentrations of approximately 1 nM. The method was employed for the
      detection of Abeta secreted from a stable transfected human neuroglioma cell line
      (H4) overexpressing a mutated form of the human amyloid precursor protein
      (APP695NL) and developed for robotic automation. At optimized conditions, signal
      to-background ratios exceeding 5 and Z' factors around 0.7 were achieved in a 384
      well format. High throughput screening of 56,913 potential Abeta production
      inhibitors led to identification of new non-cytotoxic and cell permeable
      compounds with potencies in the submicromolar range.

PMID- 15578937
TI  - Ligand.Info small-molecule Meta-Database.
AB  - Ligand.Info is a compilation of various publicly available databases of small
      molecules. The total size of the Meta-Database is over 1 million entries. The
      compound records contain calculated three-dimensional coordinates and sometimes
      information about biological activity. Some molecules have information about FDA
      drug approving status or about anti-HIV activity. Meta-Database can be downloaded
      from the http://Ligand.Info web page. The database can also be screened using a
      Java-based tool. The tool can interactively cluster sets of molecules on the user
      side and automatically download similar molecules from the server. The
      application requires the Java Runtime Environment 1.4 or higher, which can be
      automatically downloaded from Sun Microsystems or Apple Computer and installed
      during the first use of Ligand.Info on desktop systems, which support Java (Ms
      Windows, Mac OS, Solaris, and Linux). The Ligand.Info Meta-Database can be used
      for virtual high-throughput screening of new potential drugs. Presented examples
      showed that using a known antiviral drug as query the system was able to find
      others antiviral drugs and inhibitors.

PMID- 15578938
TI  - Peptide protein binding assay using ImageFlashPlates or Imaging Beads.
AB  - Imaging devices used for the measurement of radioligand-receptor binding assays
      are typically based on charge-coupled device (CCD) cameras, which are more
      sensitive for red-shifted scintillation. In the past, red-shifted scintillants
      had only been integrated into microspheres, referred to as scintillation
      proximity assay (SPA) Imaging Beads. More recently, ImageFlashPlates have been
      developed that emit light at 615 nm when exposed to beta-radiation. In this
      article, we report the establishment of peptide-protein binding assays using
      either streptavidin-coated ImageFlashPlates or Imaging Beads in a low volume 384
      well format. In these assays, we employed a biotinylated peptide X and a [33P]
      phosphorylated protein Y as the binding partner. The FlashPlates required a
      washing step, the bead-filled microtiter plates (MTPs) needed a centrifugation
      step for optimal performance in the scintillation measurements. Both the peptide
      X-loaded FlashPlates and the beads displayed saturable binding of [33P]
      phosphorylated protein Y with a similar scintillation efficiency. A KD value of
      about 30 nmol/l was measured using the bead-based assay. Due to the washing step
      in the FlashPlate experiment, approximately two-thirds of the [33P]
      phosphorylated protein Y were withdrawn from equilibrium binding. This resulted
      in correspondingly lower scintillation signals for the FlashPlate experiment. For
      this reason, the FlashPlate produced a Z' value of 0.64 that was lower than the
      Z' value of 0.87 for the beads. Using a reference inhibitor in a competition
      assay produced similar IC50 values for the bead-based assay as for the
      FlashPlate. Depending on the local automation environment either the
      centrifugation step for the beads or the washing step for the FlashPlates may be
      considered more or less of a challenge. Low volume 384-well high-throughput
      screening (HTS) applicable assay formats are achievable using either the
      ImageFlashPlates or the Imaging Beads.

PMID- 15578939
TI  - Molecular diversity management strategies for building and enhancement of diverse
      and focused lead discovery compound screening collections.
AB  - This publication describes processes for the selection of chemical compounds for
      the building of a high-throughput screening (HTS) collection for drug discovery,
      using the currently implemented process in the Discovery Technologies Unit of the
      Novartis Institute for Biomedical Research, Basel Switzerland as reference. More
      generally, the currently existing compound acquisition models and practices are
      discussed. Our informatics, chemistry and biology-driven compound selection
      consists of two steps: 1) The individual compounds are filtered and grouped into
      three priority classes on the basis of their individual structural properties.
      Substructure filters are used to eliminate or penalize compounds based on
      unwanted structural properties. The similarity of the structures to reference
      ligands of the main proven druggable target families is computed, and drug
      similar compounds are prioritized for the following diversity analysis. 2) The
      compounds are compared to the archive compounds and a diversity analysis is
      performed. This is done separately for the prioritized, regular and penalized
      compounds with increasingly stringent dissimilarity criterion. The process
      includes collecting vendor catalogues and monitoring the availability of samples
      together with the selection and purchase decision points. The development of a
      corporate vendor catalogue database is described. In addition to the selection
      methods on a per single molecule basis, selection criteria for scaffold and
      combinatorial chemistry projects in collaboration with compound vendors are
      discussed.

PMID- 15578940
TI  - Normalization of cDNA microarray data using wavelet regressions.
AB  - Normalization is an essential step in microarray data mining and analysis. For
      cDNA microarray data, the primary purpose of normalization is removing the
      intensity-dependent bias across different slides within an experimental group or
      between multiple groups. The locally weighted regression (lowess) procedure has
      been widely used for this purpose but can be comparatively time consuming when
      the dataset becomes relatively large. In this study, we applied wavelet
      regressions, a new smoothing method for recovering a regression function from
      data that is supposed to outperform other methods in many cases, such as spline
      or local polynomial fitting, to normalize two cDNA microarray datasets. Relative
      to the lowess procedure, we found that wavelet regressions not only produced
      reliable normalization results but also ran much faster. The computing speed
      represents one of the most important advantages over other algorithms, especially
      when one is interested in analyzing a large microarray experiment involving
      hundreds of slides.

PMID- 15578941
TI  - Probability issues in molecular design: predictive and modeling ability in 3D
      QSAR schemes.
AB  - In the current work we investigated 3D-QSAR data by the use of the coupled leave
      several-out (LSO) and leave-one-out (LOO) cross-validation (CV) procedures. We
      verified the above mentioned scheme using both simulated data and real 3D QSAR
      data describing a series of CoMFA steroids, heterocyclic azo dyes and
      styrylquinoline HIV integrase inhibitors. Unlike in standard analyses, this
      technique characterizes individual method not by a single performance metrics but
      screens a whole possible modeling space by sampling different molecules into the
      training and test sets, respectively. This allowed us for the discussion of the
      information included in the estimators validating cross-validation procedures, as
      well as the comparison of the efficiency of several 3D QSAR schemes, in
      particular, Comparative Molecular Field Analysis (CoMFA) and Comparative
      Molecular Surface Analysis (CoMSA). Moreover, it allows one to acquire some
      general knowledge about predictive and modeling ability in 3D QSAR method.

PMID- 15578942
TI  - Methods to assess tissue-specific distribution and metabolism of drugs.
AB  - Most drugs exert their effects not within the plasma compartment, but in defined
      target tissues into which drugs have to distribute from the central compartment.
      Unfortunately, a complete and lasting equilibration between blood and tissue
      cannot always be taken for granted. Drug distribution processes may be
      characterized by a high intertissue- and intersubject variability and target site
      drug levels may substantially differ from corresponding plasma levels. Suboptimal
      target site concentrations may have important clinical implications, as it is a
      potential explanation for therapeutic failures. Therefore, determination of drug
      tissue penetration plays an important role in clinical drug development. In
      recent years, the assessment of tissue concentrations after administration of
      very low, sub-pharmacological drug amounts (microdosing) has attracted major
      interest in early clinical drug development, which calls for the availability of
      highly sensitive analytical methods. The present article will review the most
      important techniques that are currently available for studying drug disposition
      in humans. These can be classified as semi-invasive (microdialysis, MD) and non
      invasive (positron emission tomography, PET, and magnetic resonance spectroscopy,
      MRS). We will discuss individual strengths and shortcomings of each method and
      provide some recent examples with particular focus on antiinfective and
      anticancer drugs. Whereas MD and MRS also lend themselves to the assessment of
      tissue-specific drug metabolism, PET usually does not provide metabolic
      information. For some drugs, such as the anticancer agents 5-fluorouracil and
      capecitabine, measurement of drug metabolites is particularly important as these
      represent the therapeutically active species.

PMID- 15578943
TI  - CYP3A4 induction by xenobiotics: biochemistry, experimental methods and impact on
      drug discovery and development.
AB  - Cytochrome P450 3A4 (CYP3A4), an enzyme that is highly expressed in the human
      liver and small intestine, plays a major role in the metabolism of a large
      variety of xenobiotics, including an estimated 50% of therapeutic drugs, as well
      as many endogenous compounds. The expression of CYP3A4 can be induced by
      xenobiotics. Such induction leads to accelerated metabolism of the xenobiotics
      themselves (autoinduction) or of concomitantly administered CYP3A4
      substrates/drugs, thereby significantly altering their pharmacokinetic and
      pharmacodynamic profiles. During the past decade, much progress has been made in
      our understanding of the biological mechanisms responsible for regulation of
      CYP3A4 expression. It is now known that many xenobiotics induce CYP3A4 expression
      via the pregnane X receptor (PXR) pathway, while others are thought to act
      through the constitutive androstane receptor (CAR) and the vitamin D receptor
      (VDR). As a result, most pharmaceutical companies have recognized that it is
      important to evaluate CYP3A4 induction potential preclinically and are using
      primary cultures of human hepatocytes and/or PXR reporter gene assays. In
      general, the results from these two assay methods correlate well. The reporter
      gene assays in particular can be used to rapidly screen hundreds of drug
      candidates, whereas methods using primary human hepatocyte cultures may more
      accurately assess the potential for CYP3A4 induction in vivo. Although it is
      important to consider CYP3A4 induction in the early stages of the drug
      development process, it should be recognized that the assessment of induction
      potential preclinically is a difficult and imprecise endeavor and can be
      complicated by many factors.

PMID- 15578944
TI  - Role of metabolism in ocular drug delivery.
AB  - Metabolism is one of the primary routes of drug elimination from the body. This
      process comprises of mechanisms, such as oxidation and conjugation, which lead to
      inactivation and/or elimination from hepatic, biliary, pulmonary, renal and
      ocular tissues. Enzymes involved in metabolism are expressed in various tissues
      of the body, liver being the primary site. Studies involving ocular tissues have
      demonstrated the expression of several metabolic enzymes such as esterases,
      peptidases, ketone reductases, and CYP-450's in these tissues. These enzymes play
      an important role in ocular homeostasis by preventing entry and/or eliminating
      xenobiotics from the ocular tissues. Scientists have targeted these enzymes in
      drug design and delivery through prodrug derivatization. The prodrugs undergo
      biotransformation to the parent drug by ocular enzymatic degradation. This review
      examines the distribution pattern of various metabolic enzymes in the ocular
      tissues, their physiological role and utility in targeted prodrug delivery.

PMID- 15578945
TI  - Chiral inversion of drugs: coincidence or principle?
AB  - 2-arylpropionic acid derivatives are probably the most frequently cited drugs
      exhibiting the phenomenon that is best known as chiral inversion. One enantiomer
      of drug is converted into its antipode either in the presence of a solvent or
      more often in inner environment of an organism. Mechanistic studies of the
      metabolic chiral inversion were carried out for several drugs from NSAIDs, and a
      model of this inversion was suggested and subsequently confirmed. The chiral
      inversion of NSAIDs has been intensively studied in the context of the
      pharmacological and toxicological consequences. However, the group of NSAIDs is
      not the sole group of drugs in which the inversion phenomenon can be observed.
      There exist several other drugs that also display chiral inversion of one or even
      both of their enantiomers. These drugs belong to different pharmacotherapeutic
      groups as monoamine oxidase inhibitors, antiepileptic drugs, drugs used in the
      treatment of hyperlipoproteinemia or drugs that are effective in the treatment of
      leprosy. Moreover, some chiral or prochiral drugs are metabolized to give chiral
      metabolites that undergo chiral inversion too, which can have direct impact on
      pharmacological properties or toxicity of the drug. As the process of chiral
      inversion is affected by several factors, so the intensity of chiral inversion of
      individual substances and at different conditions can differ considerably.
      Interspecies differences and types of tissue are reported to be the main factors
      that were recognized to play the key role in the process of chiral inversion.
      Some of more recent studies have revealed that several other factors, such as the
      route of administration or interaction with other xenobiotics, can influence the
      enantiomeric conversion, too. Chiral inversion does not seem to be a phenomenon
      connected with only several drugs from some unique group of 2-arylpropionic acid
      derivatives: it is also observed in drugs with rather different chemical
      structures and is much more frequent than it can be realized.

PMID- 15578946
TI  - NOx and R-NOx: effects on drug metabolism.
AB  - A family of three nitric oxide synthase 1(NOS) isoforms produces nitric oxide
      (NO*) and L-citrulline via a stepwise oxidation of the guanidinium nitrogen of L
      arginine. Akin to cytochrome P450 (P450)-catalyzed monoxygenations, the NOS
      reactions are dependent on both molecular oxygen and NADPH. Although all three
      NOS isoforms (two constitutively-expressed isoforms; neuronal (nNOS) and
      endothelial (eNOS), and one inducible isoform; (iNOS)) produce identical
      products, the function of the NO* varies widely in terms of physiological
      functions due to the varied localization of the isoforms within different cell
      populations of the body. The NOS isoforms are homo-dimeric, bi-domain enzymes.
      Each monomer consisting of a flavin-containing reductase domain linked to a heme
      containing oxygenase domain by a calmodulin (CaM)-binding sequence located
      between the two domains. The reductase domains of the NOS isoforms not only
      possess close sequence and structural homology to NADPH-cytochrome P450
      oxidoreductase (CPOR), but also, owing to the flavins, resemble CPOR in function
      in that the reductase permits the passage of electrons from a NADPH-derived
      hydride, one at a time, to the NOS oxygenase domain. Although possessing very
      little structural resemblance to P450, the oxygenase domain of NOS is referred to
      as being "P450-like" due to the presence of iron protoporphyrin IX (heme), linked
      axially by a cysteine to the NOS protein, which carries out "P450-like" mono
      oxygenation reactions. Considering the importance of NO* in regulating many
      physiological functions, the NOS isoforms are important drug targets. Modulators
      (both inhibitors as well as possible activators) of enzymatic function are needed
      to either decrease or increase NO* production, respectively, in various disease
      states. In addition to the widely known beneficial processes where NO* plays a
      role (i.e. neurotransmission, blood pressure regulation, immunomodulation), under
      certain conditions production of NO* (as well as other NOS-derived oxidants) can
      be detrimental by altering enzyme activity; for example P450-mediated drug
      metabolism. Furthermore, because of the close structural and functional
      similarities between NOS reductase and CPOR, many of the same redox-cycling and
      reductive reactions that occur with CPOR can also occur with NOS. The final focus
      of this review article is the less-well-recognized reactions mediated by NOS,
      which have recently begun to receive the attention they deserve. We hope to
      highlight reasons for concern regarding both altered drug metabolism as well as
      extra-hepatic, and target-organ toxicities in response to both altered NO*
      production as well as the detrimental interaction of NOS with certain
      xenobiotics.

PMID- 15578947
TI  - Metabolism of antiarrhythmics.
AB  - Antiarrhythmics are a group of drugs that manage the irregular electrical
      activity of the heart. Their use in the clinic is made difficult by their narrow
      therapeutic index. The disposition of antiarrhythmics is dependent on many
      factors, such as administration route, stereoselectivity in the first-pass
      effect, inhibition of enzymes, polymorphisms, etc. Consequently, the
      pharmacological activity of drugs may be interindividually variable. Experiments
      using organ homogenates or hepatic microsome fractions were used for simulating
      the biotransformation of the drug in vivo. The classical approaches, such as
      correlation analysis, specifically the inhibitory effect, or induction of
      chemicals, and immunoinhibition, may be combined with the use of recombinant
      enzymes for identifying the enzymes involved in the drug metabolism. The fate of
      the antiarrhythmics may also be investigated in live animals. A species-dependent
      metabolism was often observed. The pre-treatment with chemicals, which influences
      the change (inhibition or induction) in the drug disposition, may provide
      insights into the enzymes involved in vivo. However, published data indicated
      that the data obtained from animals should not be extrapolated directly to
      humans. Nevertheless, animal models are useful for investigating the mechanism of
      clinical observations. The clinical use of the antiarrhythmics becomes complex,
      when the drug metabolism is genetically/phenotypically dependent and active
      metabolites are formed. Furthermore, the stereoselectivity may also modify the
      disposition and the pharmacodynamic profile of a therapeutic agent. Only the
      knowledge of the drug metabolism and the status of each individual may allow the
      use of antiarrhythmics safely.

PMID- 15578948
TI  - Ribozyme- and deoxyribozyme-strategies for medical applications.
AB  - Ribozymes are catalytically active nucleic acids capable of site-specific
      cleavage of target mRNAs. They have widely been employed as tools in functional
      studies and for therapeutic purposes. Different classes of ribozymes
      distinguished by size and mechanism of action have been discovered in natural
      systems or obtained by in vitro selection. After an introduction to different
      types of ribozymes with a special focus on the hammerhead and hairpin ribozyme,
      major challenges in the process of developing ribozymes for medical purposes will
      be described in the present review. Subsequently, examples of ribozyme
      applications in animal models for various diseases including cancer, viral
      infections, rheumatoid arthritis and cardiovascular diseases will be given. The
      course of phase I and II clinical trials with ribozymes designed to treat
      patients with virus infections or cancer will be outlined. Finally, the current
      significance of ribozymes will be discussed in the light of the emergence of new
      powerful anti-mRNA strategies, particularly RNA interference (RNAi).

PMID- 15578949
TI  - Killing the messenger: antisense DNA and siRNA.
AB  - Among the technologies available for gene knockdown RNase H-dependent antisense
      oligonucleotides and RNAi are very popular. Both offer specificity and efficient
      knockdown of the genes; both are useful tools to study gene functions. Antisense
      and RNAi methods share many practical problems such as site selection, toxicity
      at high concentration, and the difficulty of transfection in certain cell types.
      We will focus in this review on the most important issues in the development of
      both methods and their possible use in gene-silencing therapy.

PMID- 15578950
TI  - Triplex-forming oligonucleotides - sequence-specific DNA ligands as tools for
      gene inhibition and for modulation of DNA-associated functions.
AB  - The down regulation of gene expression is a promising strategy for molecular
      medicine and experimental biology. Molecules that bind to the DNA double helix
      may interfere with gene expression and, in addition to potential therapeutic
      applications, can be helpful for the investigation of DNA processing, chromatin
      package, or associated biological processes. Triplex-forming oligonucleotides
      (TFOs) bind to specific sequences in the DNA double helix via hydrogen bonding
      interactions. TFOs have been shown to down-regulate gene expression, to induce
      targeted genomic DNA modifications, to stimulate DNA recombination, and to
      modulate chromatin organization. Additionally, they may be used as carriers to
      position DNA-modifying agents to selected sequences. TFO-mediated effects have
      been mostly described in cell culture, but one study reported TFO activity in a
      mouse model. Critical issues regarding TFO-based technologies are the development
      of new oligonucleotide analogues with improved binding affinity, better target
      selectivity, and sufficient stability in the intracellular environment. A
      prerequisite for the development of such DNA-binding molecules is the
      availability of appropriate methods to assess their binding properties
      quantitatively at the desired target sequence in the genome. This review focuses
      on recent results regarding gene-inhibitory effects of TFOs in cell culture and
      methods to evaluate TFO-binding to the desired target sequence in the context of
      the human genome.

PMID- 15578951
TI  - Progress in thioaptamer development.
AB  - Thioaptamers are thiophosphate ester modified nucleic acids that are isolated via
      in vitro or bead-based thioaptamer selection against a target molecule such as a
      protein. Thioaptamers offer advantages over traditional aptamers in their
      enhanced affinity and specificity and higher stability, largely due to the
      properties of the sulfur backbone-modifications. An in vitro thioaptamer
      selection procedure that simultaneously selects for sequence and optimized hybrid
      phosphoromonothioate or phosphate backbone substitutions is outlined. A novel
      bead-based thioaptamer selection protocol that can produce mixed
      phosphorodithioate, phosphoromonothioate or phosphate hybrid backbones is also
      described. Several examples of thioaptamers targeting specific protein are
      provided. Such thioaptamers are shown to modulate protein activity in vivo.

PMID- 15578952
TI  - Application of decoy oligodeoxynucleotides-based approach to renal diseases.
AB  - Recent progress in cellular and molecular research has provided a new technique
      to inhibit target gene expression based on DNA technology such as antisense
      oligodeoxynucleotides (ODN), small interfering RNA (siRNA), ribozyme and decoy
      ODN. Especially, recently, a successful ODN-based approach termed decoy ODN has
      used synthetic ODN containing an enhancer element that can penetrate cells, to
      bind to sequence-specific DNA-binding proteins and interfere with transcription
      in vitro and in vivo. Transfer of cis-element double-stranded decoy ODN has been
      reported as a new powerful tool in a new class of anti-gene strategies to treat
      various diseases as gene therapy or as a research tool to examine the molecular
      mechanisms of expression of a specific gene. Transfer of double-stranded ODN
      corresponding to the cis-sequence will result in attenuation of the authentic cis
      trans interaction, leading to removal of trans-factors from the endogenous cis
      elements with subsequent modulation of gene expression. To date, we have chosen
      several target transcription factors such as nuclear factor-kappaB (NF-kappaB)
      and E2F to prevent the progression of several diseases including renal diseases.
      As other targets, we focused on negative regulatory element (NRE) for the renin
      gene and angiotensinogen gene-activating element (AGE) for the angiotensinogen
      gene to examine the molecular mechanisms of gene expression, AP-1 and ets-1. In
      this paper, we introduce the decoy strategy and demonstrate examples of
      application of decoy ODN approach targeting E2F and NF-kappaB in renal diseases.

PMID- 15578953
TI  - Peptide nucleic acids (PNA)-DNA chimeras targeting transcription factors as a
      tool to modify gene expression.
AB  - Peptide nucleic acids (PNAs)-DNA chimeras have been recently described as DNA
      mimics constituted of a part of PNA and of a part of DNA. We have demonstrated
      that double stranded molecules based on PNA-DNA chimeras bind to transcription
      factors in a sequence-dependent manner. Accordingly, these molecules can be used
      for transcription factor decoy (TFD) pharmacotherapy. Effects of double stranded
      PNA-DNA chimeras targeting NF-kappaB and Sp1 were determined on in vitro cultured
      human cells and were found to be comparable to those observed using double
      stranded DNA decoys. The TFD molecules based on PNA-DNA chimeras can be further
      engineered by addition of short peptides facilitating cell penetration and
      nuclear localization. Therefore, these engineered molecules could be of great
      interest for in vivo experiments for non-viral gene therapy of a variety of
      diseases, including neoplastic and viral diseases, for which the TFD approach has
      been already demonstrated as a very useful strategy.

PMID- 15578954
TI  - Locked nucleic acids (LNA): versatile tools for designing oligonucleotide decoys
      with high stability and affinity.
AB  - Double-stranded oligodeoxynucleotides (ODN) containing the consensus binding
      sequence of a transcription factor are valuable tools for the manipulation of
      gene expression at the transcriptional level by means of the decoy strategy. The
      approach involves flooding the cells with enough ODN decoy to compete for binding
      of the transcription factor with its consensus sequence in target genes. The
      technique has been proven effective in vitro and in vivo, suggesting its use in
      therapy. Therefore, great attention has been recently focused on chemical
      modifications enhancing biostability of the oligonucleotides so as to improve
      their pharmacological properties. Unfortunately, benefits in terms of nuclease
      resistance have been often negated by a decrease in the affinity and/or
      specificity of transcription factor binding. To circumvent these problems,
      circular dumbbell and chimeric decoy oligonucleotides, the latter comprising a
      central stretch of transcription factor recruiting deoxynucleotides flanked by
      modified nucleotides, have been introduced. Nevertheless, these approaches have
      the limitation of leaving the ODNs still sensitive to endonuclease cleavage. To
      address these concerns, we have recently investigated the use of a new class of
      nucleotide analogs termed locked nucleic acids (LNA) in the designing of decoy
      molecules for the transcription factor kappaB (NF-kappaB). In this article, we
      review the advantages of LNA in the design of ODN decoys pointing to the
      feasibility of introducing modifications in the transcription factor binding
      sequence in order to obtain molecules with increased stability compared to end
      capped ODNs, while remaining efficiently recognized by NF-kappaB.

PMID- 15578955
TI  - In vivo imaging of oligonucleotides with nuclear tomography.
AB  - Positron emission tomography (PET) and single photon emission tomography (SPECT)
      are high-resolution, sensitive, molecular and functional imaging techniques that
      permit repeated, noninvasive assessment and quantification of specific biological
      and pharmacological processes in humans. PET and SPECT are also the most advanced
      technologies currently available for studying in vivo molecular interactions and
      therefore can advantageously play a key role in both drug discovery and
      development of pharmaceuticals, by assessing their in vivo distribution,
      pharmacokinetics, and dynamics, once labeled with a positron or gamma-emitter.
      Recent advances in positron and gamma-emitter labeling of bioconjugates allow the
      design and development of complex high-molecular-weight bioactive chemical
      structures as radiopharmaceuticals including single-stranded oligonucleotides.
      Besides, the introduction of high-resolution tomographic devices for imaging the
      distribution of radioactivity in small animal models such as mice and rats offers
      a unique opportunity to study the biological behavior of labeled compounds in
      integrated, unperturbed living systems. The present review illustrates the
      current technologies for labeling oligonucleotides with various radioisotopes,
      and their use as in vivo probes of oligonucleotide distribution and molecular
      interactions in target tissues. Emphasis will be also given to the role which
      could be played by these technologies in the development of oligonucleotide-based
      drugs.

PMID- 15578956
TI  - Platelet aggregation and exogenous factors from animal sources.
AB  - Platelet aggregation plays a crucial role in thrombosis. This review describes
      exogenous factors isolated from various animal sources, including venoms and the
      salivary glands that interfere in platelet aggregation. Some of these factors
      induce platelet aggregation or agglutination, whereas others inhibit platelet
      aggregation. These proteins range from small molecular weight peptides to large
      proteins. Some of these proteins exhibit various enzymatic activities, while
      others are nonenzymatic. These exogenous factors affect platelet aggregation by
      various mechanisms and thus they have been classified based on their mechanism of
      action. Many of these proteins have evolved through both convergent and divergent
      evolution. For example, platelet aggregation inhibitors, which interfere in the
      interactions between fibrinogen and its receptor, the glycoprotein IIb/IIIa
      complex, show extreme structural diversity but they share the common functional
      site of Arg-Gly-Asp (RGD) tripeptide segment. On the other hand, C-type lectin
      related proteins exhibit diverse biological effects by interacting with different
      proteins, but share common structural scaffold. Thus the mechanistic and
      structure-function studies of these exogenous proteins have contributed
      significantly to the understanding of molecular mechanisms of platelet
      aggregation and to the development of potent antiplatelet agents, respectively. A
      number of new exogenous factors have been identified recently and the search is
      still on for novel factors that interfere with platelet aggregation. Further
      studies in this area will help in the development of novel strategies for
      treating cardiovascular and hematological disorders.

PMID- 15578957
TI  - Disintegrins.
AB  - The existence of disintegrins, non-enzymatic, small molecular weight proteins
      from viper venom, has been known for 2 decades, and their impact on cellular
      research has been substantial and far-reaching. Disintegrins have been the
      molecular scaffold used in the design of therapeutics for the prevention of
      thrombosis and cancer. Their sequencing has provided insights into the evolution
      of proteins over millennia. Production of recombinant disintegrin mutants and
      fusion proteins has allowed investigations into molecular mechanisms at work in
      cell-extracellular matrix interactions. Structural homologies with non-snake
      proteins have shown disintegrin-like molecules in species ranging from slime mold
      to humans. Intracellular signaling events have been elucidated through the use of
      venom disintegrins, including events related to programmed cell death, motility,
      cell proliferation and viral pathogenesis. Disintegrin sequences (protein or
      genes) have been placed in microbubbles and liposomes and been found to target
      neovascular endothelium and metastatic tumors in two mouse models. The purpose of
      this review is to highlight the members of this disintegrin family discovered
      since 1998 as well as the increased understanding of their usefulness in
      therapeutics and technical assays.

PMID- 15578958
TI  - C-type lectin-related proteins from snake venoms.
AB  - C-type lectin-like proteins (CLPs) of snake venom have a variety of biological
      properties, acting for example as anticoagulants, procoagulants, and
      agonists/antagonists of platelet activation. The structural and functional
      studies of the first identified CLP, factor IX/factor X-binding protein, have led
      to an understanding how new functionally heterodimeric CLPs from monomeric C-type
      lectin related proteins may have evolved by 3D domain swapping, and have
      contributed to our understanding of the significance of magnesium ions in the
      blood coagulation cascade reaction. Two metallo-proteases, carinactivase and RVV
      X (factor X activator of a snake venom), with C-type lectin-like domains, were
      isolated, characterized, and found to be useful in the study of the properties of
      prothrombin and coagulation factor X. There are also several unique CLPs belong
      to agonists and antagonists of platelet receptors, platelet glycoprotein Ib and
      glycoproteins Ia/IIa and VI, collagen receptors and the following CLPs that
      modulate platelet function. These CLPs may provide the new insights into platelet
      function: alboaggregin-B, echicetin, botrocetin, bitiscetin, flavocetin-A,
      aggretin/rhodocytin, convulxin, and agkistin.

PMID- 15578959
TI  - Antihemostatic strategies of blood-feeding arthropods.
AB  - Arthropods in at least 23 different families or orders, distributed between two
      classes (Insecta and Arachnida), feed on vertebrate blood. They are able to do
      this despite constraints imposed by a sophisticated array of hemostatic defenses,
      due to the presence of a wide range of antihemostatic molecules in their saliva,
      including vasodilators, antiplatelet factors, and anticoagulants. Vasodilators
      include amines, prostaglandins, peptides, proteins, and even a mechanism to store
      large amounts of nitric oxide and deliver it into the skin. Platelet aggregation
      inhibitors include nitric oxide, prostaglandins, apyrase, molecules that
      sequester ADP, and a range of peptides and proteins that interact specifically
      with integrin receptors. Anticoagulants include a wide variety of inhibitors that
      target thrombin and factor Xa, as well as proteins that disrupt the "tenase",
      prothrombinase, and tissue factor/FVIIa complexes. The potential complexity of
      saliva is illustrated with the example of Rhodnius prolixus, which contains a
      large array of compounds, many of which affect more than one target in the
      hemostatic process. Finally a brief discussion of a new approach (sialomics) to
      the discovery of pharmacological agents in arthropod saliva is presented.

PMID- 15578960
TI  - Snake venom prothrombin activators similar to blood coagulation factor Xa.
AB  - Activation of prothrombin to mature thrombin in vivo occurs by the proteolytic
      action of the prothrombinase complex consisting of serine proteinase factor Xa,
      and cofactors that include factor Va, Ca(2+) ions and phospholipids. Several
      exogenous prothrombin activators are found in snake venom. Among these, Group C
      prothrombin activators resemble the factor Xa-factor Va complex, while Group D
      activators are structurally and functionally similar to factor Xa. This review
      provides a detailed description of current knowledge on Group D prothrombin
      activators and highlights the importance of studying this family of proteins in
      enhancing our understanding of structure-function relationships in the mammalian
      prothrombinase complex.

PMID- 15578961
TI  - Alpha-fibrinogenases.
AB  - Snake venoms contain a number of serine and metalloproteinases, included among
      these are the fibrinolytic metalloproteinases. When the fibrinolytic enzymes were
      first isolated from viper venoms it was postulated that there may be a clinical
      application for these enzymes in the treatment of occlusive thrombi, such as
      those occurring in the great arteries and veins of cardiac and cerebral
      circulation as well as peripheral arteries and veins. In the ensuing years a
      substantial body of literature has been generated on the identification and
      characterization of the fibrinolytic enzymes from a broad spectrum of snake
      species. In this report we describe the biological properties and positive
      clinical features of the class of enzymes known as alpha-fibrinogenases.
      Fibrolase, a fibrinolytic metalloproteinase originally isolated from Agkistrodon
      contortrix contortrix venom, is the representative fibrinolytic enzyme used for
      the description and characterization of the alpha-fibrinogenases in this chapter.
      The biochemical and physiochemical properties and in vivo activity of the enzyme
      are described as well as in vitro studies using a platelet avid chimera of
      fibrolase. The chimera was formed by coupling fibrolase to an Arg-Gly-Asp (RGD)
      like peptide imparting inhibitory activity on platelet aggregation and thrombus
      formation, while maintaining full fibrinolytic activity. Fibrolase has also been
      modified through the adduction of polyethylene glycol to reduce the rate of
      clearance from the circulation. In this review we also include a description of
      alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase, and follow
      the development of the enzyme as a potential clinical agent in the clearance of
      occlusive thrombi. Alfimeprase is presently in clinical trials for two
      indications: the treatment of peripheral arterial occlusions (in which phase II
      is nearing successful completion), and for use in the clearance of occluded
      vascular access catheters in direct competition with plasminogen activators.

PMID- 15578962
TI  - Hypotensive agents from snake venoms.
AB  - Many snake venoms contain toxins which produce profound cardiovascular effects.
      The site of action of these toxins includes cardiac muscle, vascular smooth
      muscle and the capillary vascular bed. Some snake venoms, for example, contain
      peptides that inhibit angiotensin converting enzyme and potentiate the biological
      actions of bradykinin. Other snake venoms contain structural and functional
      equivalents of mammalian natriuretic peptides. Sarafotoxins are short peptide
      toxins found in the venoms of snakes from Atractaspis spp. which display potent
      vasoconstriction properties. These peptides, which share a high degree of
      sequence identity with endothelins, recognize and bind to endothelin receptors.
      Snakes have also evolved toxins which block L-type Ca(2+) currents (eg.
      calciseptine, FS2 toxins, C(10)S(2)C(2) and S(4)C(8)). Snake venom proteins have
      also been shown to increase vascular permeability. One such protein, increasing
      capillary permeability protein (ICPP) has recently been isolated from the venom
      of Vipera lebetina. ICPP is an extremely potent permeability factor with a
      structure similar to vascular endothelial growth factor (VEGF). Thus there is a
      vast array of snake toxins with potent cardiovascular activity. Some of these
      proteins and peptides have proven to be highly selective tools in the study of
      physiological processes. Others have been used as probes of potential therapeutic
      targets or as lead compounds in the development of therapeutic agents. Therefore
      these and other related snake venom proteins hold great promise in the future
      understanding and treatment of cardiovascular diseases.

PMID- 15578963
TI  - Voltage-gated sodium channels and pain.
AB  - Voltage-gated sodium channels are highly specialized molecular transducers that
      play a significant role in the creation and transmission of electrical activity
      throughout the neuraxis. These ion channels are fundamentally involved in sensory
      neuron physiology and pathophysiology; a complete but localized suspension of
      their normal function can prevent all sensation--including that perceived as
      pain. Soft-tissue injuries that result in inflammation or direct damage to nerve
      fibers have each been shown to result in abnormal sodium channel function and, in
      many cases, to lead to pathological hyperexcitability in the sensory afferent
      nerves that innervate the injured dermatome or visceral organ. Abrogating
      abnormal activity whilst leaving normal sensation unaffected would represent a
      powerful approach to pain relief. This article reviews the evidence supporting
      abnormal sodium channel biology in various pathological contexts, the
      opportunities that this presents for novel therapeutics and progress towards
      realizing this goal.

PMID- 15578964
TI  - Voltage-gated calcium channels as targets for the treatment of chronic pain.
AB  - This review focuses on the importance of voltage-gated calcium channels in
      modulating and controlling the function of peripheral and central neurons
      involved in nociceptive processing. We describe the different families of voltage
      gated calcium channels that are expressed in pain pathway neurons, how the
      expression levels of calcium channel currents change in chronic pain conditions,
      and the validation of N-type, T-type, and P-type calcium channels as targets for
      the treatment of pain. The molecular mechanism of action is reviewed for the most
      prominent calcium channel-targeted drugs including gabapentin and ziconotide as
      well as antiepileptics administered off-label for the treatment of pain. We
      discuss how the major genetic, functional, and pharmacological differences
      between subtypes of neuronal calcium channels can be leveraged to identify new
      molecular targets and to discover and develop new therapeutic agents for the
      treatment of chronic pain syndromes.

PMID- 15578965
TI  - Nociception and TRP Channels.
AB  - Noxious thermal, mechanical, or chemical stimuli evoke pain through excitation of
      the peripheral terminals called nociceptor, and many kinds of ionotropic and
      metabotropic receptors are involved in this process. Capsaicin receptor TRPV1 is
      a nociceptor-specific ion channel that serves as the molecular target of
      capsaicin. TRPV1 can be activated not only by capsaicin but also by noxious heat
      (with a thermal threshold >43 degrees C) or protons (acidification), all of which
      are known to cause pain in vivo. Studies using TRPV1-deficient mice have shown
      that TRPV1 is essential for selective modalities of pain sensation and for
      thermal hyperalgesia. One mechanism underlying inflammatory pain which is
      initiated by tissue damage/inflammation and characterized by hypersensitivity is
      sensitization of TRPV1. In addition to TRPV1, there are five thermosensitive ion
      channels in mammals, all of which belong to the TRP (transient receptor
      potential) super family. These include TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1.
      These channels exhibit distinct thermal activation thresholds (> 52 degrees C for
      TRPV2, > approximately 34-38 degrees C for TRPV3, > approximately 27-35 degrees C
      for TRPV4, < approximately 25-28 degrees C for TRPM8 and < 17 degrees C for
      TRPA1) and are expressed in primary sensory neurons as well as other tissues.
      Some of the thermosensitive TRP channels are likely to be involved in thermal
      nociception, since their activation thresholds are within the noxious range of
      temperatures.

PMID- 15578966
TI  - GABA puts a stop to pain.
AB  - A lack of inhibition, particularly that mediated by gamma-amino butyric acid
      (GABA), the main inhibitory transmitter of the central nervous system (CNS), is
      responsible for many pain states. Until recently, few GABA acting drugs were
      available and were prescribed mostly for relieving muscle spasms, anxiety and
      epilepsy, but rarely for pain. The basic metabolic pathway of GABA is well known
      and we are now beginning to understand the function of this neurotransmitter in
      the complex circuitry underlying pain, especially in the context of nerve injury.
      Analgesic compounds are now being developed targeting GABA transporters as well
      as GABA associated enzymes and receptors. Some GABA analogs act by inhibiting ion
      channels, a property that contributes to their analgesic effects. However,
      despite considerable progress in developing new compounds, the use of
      systemically acting GABAergic drugs is limited by unwanted side-effects on
      systems other than those involved in pain, and by the fact that in certain areas
      of the brain, GABA can enhance rather than reduce pain. The advent of new drugs
      targeting subtypes of GABA receptors and transporters and the possibility of
      using newly developed delivery systems, such as intrathecal pumps and viral
      vectors, to target specific areas of the nervous system will likely help
      circumvent these problems.

PMID- 15578967
TI  - Therapeutic potential of cannabinoids in trigeminal neuralgia.
AB  - Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial
      pain and continues to be a real therapeutic challenge to the clinicians. While
      the exact cause and pathology of this disorder is uncertain, it is thought that
      trigeminal neuralgia caused by irritation of the trigeminal nerve. This
      irritation results from damage due to the change in the blood vessels, the
      presence of a tumor or other lesions that cause the compression of the trigeminal
      root. The pain of trigeminal neuralgia is characterized by unilateral pain
      attacks that start abruptly and last for varying periods of time from minutes to
      hours. The quality of pain is usually sharp, stabbing, lancinating, and burning.
      The attacks are initiated by mild stimuli such as light touch of the skin,
      eating, chewing, washing the face, brushing the teeth, and exposure to wind.
      Although antiepileptic drug therapy may be beneficial in the treatment of
      trigeminal neuralgia, up to one-half of the patients become refractory or
      intolerant to these medications. At present there are few other effective drugs.
      In cases of lacking effect after pharmacotherapy, surgical options may be
      considered. Currently there is growing amount of evidence to suggest that the
      psychoactive ingredient in cannabis and individual cannabinoids may be effective
      in alleviating neuropathic pain and hyperalgesia. Evidence suggests that
      cannabinoids may prove useful in pain modulation by inhibiting neuronal
      transmission in pain pathways. Considering the pronounced antinociceptive effects
      produced by cannabinoids, they may be a promising therapeutic approach for the
      clinical management of trigeminal neuralgia.

PMID- 15578968
TI  - New aminoacyl-tRNA synthetase inhibitors as antibacterial agents.
AB  - Increasing rates of bacterial resistance to known classes of antibiotics present
      a severe global challenge. As a consequence, the search for new chemical entities
      that address novel bacterial targets remains ongoing. Aminoacyl-tRNA synthetases
      (aa-RS) are essential enzymes for protein biosynthesis and emerged as an
      interesting target class in antibacterial research. These enzymes are present in
      all living organisms, and they are indispensable for the highly specific
      translation of the messenger-RNA (mRNA) template into protein via specific
      transfer-RNAs (tRNAs) as adapter molecules. When one aa-RS is inhibited, the
      corresponding tRNA is not charged and is therefore unavailable for translation.
      This leads to protein synthesis inhibition, which, in turn, causes cell growth
      arrest. Consequently, each compound that inhibits any of the aa-RS is a potential
      antibacterial agent. The clinical utility of this principle is proven by the
      natural product Ile-RS inhibitor pseudomonic acid, which is currently marketed as
      an antibacterial agent for topical application. Various chemical structures that
      inhibit aa-RS have been identified. These inhibitors have either been isolated
      from natural sources or have been generated synthetically. The synthetic
      inhibitors are modifications of natural inhibitors, derivatives of the natural
      synthetase substrates and reaction intermediates, or have been identified by
      screening of compound libraries. The recent progress achieved with these
      different classes of aa-RS inhibitors and their antibacterial potential in vitro
      and in vivo is discussed in this review.

PMID- 15578969
TI  - The escalating challenge of vancomycin resistance in Staphylococcus aureus.
AB  - The glycopeptide antibiotic vancomycin is considered indispensable for the
      treatment of multidrug-resistant Staphylococcus aureus infections, and so the
      acquisition by these organisms of transmissible glycopeptide resistance elements
      from enterococci had been anticipated with apprehension. It was therefore a
      considerable surprise when vancomycin-intermediate S. aureus (VISA) clinical
      isolates were reported in 1997, with a novel, borderline-resistance phenotype
      acquired without genetic exchange. Clinical vancomycin-resistant S. aureus (VRSA)
      were not reported until 2002, expressing high level, transmissible resistance by
      virtue of vanA resistance determinants within enterococcal transposable elements
      residing on staphylococcal plasmids. This review will provide an update on the
      frustratingly variable characteristics of the VISA phenotype, focus on the
      progress made in understanding the molecular basis of the VISA resistance
      mechanism from the viewpoint of genetic regulation and cell wall stress response,
      and summarize the information currently available on VRSA. Finally, alternatives
      to vancomycin that are already available or nearing approval will be briefly
      reviewed, with attention to their limitations and potential for resistance
      development.

PMID- 15578970
TI  - Molecular mechanisms of fluoroquinolone resistance in Klebsiella.
AB  - Klebsiella are well-recognized community and nosocomial pathogens responsible for
      septicemias, urinary tract infections, pneumonia, and soft tissue infections. The
      emergence of multi-drug resistant Klebsiella is becoming a global concern. Since
      fluoroquinolones are excellent antibiotics for clinical therapy of complicated
      infections, their consumptions have increased rapidly. Coincidental with the
      increased usage of fluoroquinolones, the incidences of drug resistance have
      increased, which highlights the need for understanding the molecular mechanisms
      of fluoroquinolone resistance. Alterations in targets and reduction of
      intracellular drug accumulation are two major mechanisms involved in
      fluoroquinolone resistance. This review focuses on the mechanisms of action of
      fluoroquinolones and molecular mechanisms of drug resistance, including known and
      proposed ones, and the discussion on clinical impact of multi-drug resistance in
      Klebsiella.

PMID- 15578971
TI  - Advances in adjuvant therapy against acute bacterial meningitis.
AB  - Death and co-morbidity derived from acute bacterial meningitis remain
      unacceptably high and are mainly related to immune-mediated cerebral dysfunction.
      Cerebral edema, hydrocephalus and ischaemic cerebrovascular events are severe
      complications that eventually occur following the activation of a complex network
      of cytokines, chemokines, proteases and oxidants released after cerebrospinal
      fluid infection. The caspase pathway appears to play a central role in the
      induction and amplification of the host inflammatory response. Such overactive
      immune reactions induce brain cell damage but, importantly, they may potentially
      be blocked. Several agents have been developed aiming to counteract the
      deleterious effects of such immune imbalance. These drugs are candidates to
      become adjuvant therapy against acute bacterial meningitis in the future, in
      addition to dexamethasone. We review the current state-of-art of bacterial
      meningitis adjuvant therapy, including caspase inhibitors, antioxidants, poly
      (ADP-ribose) polymerase inhibitors, inhibitors of lipid peroxidation and
      metalloproteinase inhibitors.

PMID- 15578972
TI  - IPC synthase as a useful target for antifungal drugs.
AB  - Inositol phosphorylceramide (IPC) synthase is a common and essential enzyme in
      fungi and plants, which catalyzes the transfer of phosphoinositol to the C-1
      hydroxy of ceramide to produce IPC. This reaction is a key step in fungal
      sphingolipid biosynthesis, therefore the enzyme is a potential target for the
      development of nontoxic therapeutic antifungal agents. Natural products with a
      desired biological activity, aureobasidin A (AbA), khafrefungin, and galbonolide
      A, have been reported. AbA, a cyclic depsipeptide containing 8 amino acids and a
      hydroxyl acid, is a broad spectrum antifungal with strong activity against many
      pathogenic fungi such as Candida spp., Cryptococcus neoformans, and some
      Aspergillus spp. Khafrefungin, an aldonic acid ester with a C22 long alkyl chain,
      has antifungal activity against C. albicans, Cr. Neoformans, and Saccharomyces
      cerevisiae. Galbonolide A is a 14-membered macrolide with fungicidal activity
      against clinically important strains, and is especially potent against Cr.
      neoformans. These classes of natural products are potent and specific antifungal
      agents. We review current progress in the development of IPC synthase inhibitors
      with antifungal activities, and present structure-activity relationships (SAR),
      physicochemical and structural properties, and synthetic methodology for chemical
      modification.

PMID- 15578973
TI  - New acridone inhibitors of human herpes virus replication.
AB  - Modern biomedicinal research with acridones began with plant secondary
      metabolites but the successful development of these alkaloids into drugs has yet
      to be realized. However, there are synthetic acridones unrelated to the natural
      products now emerging as promising bioactive compounds. The purpose of this mini
      review is to highlight the renewed interest in acridones for antiviral drug
      research, with the emphasis placed on several derivatives in early stage
      development for treating herpes virus infection. Novel anti-herpes acridones
      developed using a ligand-based approach have much simpler structure and generally
      have higher selectivity than the corresponding alkaloids. Three sub-types are
      currently classified on the basis of activity against Herpes Simplex Virus (HSV)
      and, or Human Cytomegalovirus (HCMV) and all of them inhibit viral replication
      post-adsorption. In terms of mode/mechanism of action, this "second wave" of
      early generation lead molecules appears unique in comparison to the natural
      products and to drugs derived from more traditional templates. Inhibition of HSV
      replication by these agents is best understood and it occurs after viral DNA
      synthesis. The mechanism for one prototype inhibitor (5-chloro-1,3-dihydroxy
      acridone), involves a blockade of viral DNA maturation (cleavage/packaging) and
      viral capsids accumulate abnormally. Interestingly, the 7-Chloro regioisomer
      blocks a later stage of viral assembly. At this time it is unclear whether
      atypical target-interaction or unusual polypharmacology is responsible for the
      antiviral activities observed and this key issue will hamper future drug
      development until it is resolved.

PMID- 15578974
TI  - Recent advances in rhinovirus therapeutics.
AB  - Human rhinoviruses are the major causative agents of the common cold. Because
      there are greater than 100 viral serotypes, little immunological protection is
      afforded to humans by prior rhinovirus exposure, which accounts for the high
      incidence of infection. In most cases, rhinovirus leads to a short self-limiting
      illness. However, for asthmatics, the elderly and immunocompromised patients,
      rhinovirus infection can lead to life-threatening complications. This has spurred
      a consistent effort over recent decades to identify effective treatments and
      preventions for rhinovirus infection. While some work has focused on alleviating
      the symptoms induced as a result of inflammatory pathways stimulated by
      rhinoviruses, the majority of the research has been focused on limiting or
      preventing viral infection altogether. Various approaches have been taken to halt
      rhinovirus infection. Prevention of virus-cell interaction has been the aim of
      research on viral capsid binders and cell receptor blockers. Interference with
      correct viral protein processing is the goal of the design and testing of
      protease inhibitors. Current work is attempting to interfere with viral RNA
      replication by testing silencing RNA molecules. In this review, we will discuss
      recent advances in the development and testing of human rhinovirus therapeutics.

PMID- 15578975
TI  - New advances in HIV entry inhibitors development.
AB  - Considerable advances have been made in the last years in the design of
      derivatives acting as inhibitors of HIV entry and fusion. The discovery of
      chemokines focused the attention on cellular coreceptors used by the virus for
      entering within cells, and consequently the various steps of such processes have
      been characterized in detail. Intense research led to a wide range of effective
      compounds that are able to inhibit the initial steps of HIV life cycle. All steps
      in the process of HIV entry into the cell may be targeted by specific compounds
      that may be developed as novel types of antiretrovirals. Thus, several inhibitors
      of the gp120-CD4 interaction have been detected so far (zintevir, FP-21399 and
      BMS-378806 in clinical trials). Small molecule chemokine receptor antagonists
      acting as HIV entry inhibitors also were described in the last period, which
      interact both with the CXCR4 coreceptor (such as AMD3100; AMD3465; ALX40-4C; T22,
      T134 and T140), or which are antagonist of the CCR5 coreceptor (TAK-779, TAK-220,
      SCH-C, SCH-D, E913, AK-602, UK-427857 and NSC 651016 in clinical trials),
      together with new types of fusion inhibitors possessing the same mechanism of
      action as enfuvirtide (such as T1249). Recently, a third family of antivirals
      started to be used clinically (in addition to the reverse transcriptase and
      protease inhibitors), with the advent of enfuvirtide (T20), the first fusion
      inhibitor to be approved as an anti-HIV agent. Some of these compounds
      demonstrated in vitro synergism with other classes of antivirals, offering thus
      the rationale for their combination in therapies for HIV-infected individuals.
      Many HIV entry and fusion inhibitors are currently being investigated in
      controlled clinical trials, and a number of them is bioavailable as oral
      formulations. This is an essential feature for an extended use of these compounds
      with the purpose of ameliorating adherence of patients to these medications and
      preventing the development of drug resistance.

PMID- 15578976
TI  - Blocking HIV-1 Vif restores a natural mechanism of intracellular antiviral
      defense.
AB  - AIDS has become the greatest pandemic in the human history counting approximately
      40 millions people worldwide. To purge HIV-1 infection, new therapeutic
      approaches need to be searched in alternative and/or in addition to the current
      pharmacological ones. Recently, several independent laboratories have unveiled a
      non-immune intracellular anti-HIV-1 defense strategy based on the cytidine
      deaminase APOBEC3G, which restricts HIV-1 production by directly mutating the
      proviral DNA in infected cells. To counteract this defense pathway, HIV-1 has
      developed an evasion strategy by acquiring the accessory protein Vif, which
      blocks the action of APOBEC3G by inducing its proteasome-mediated degradation.

PMID- 15578977
TI  - Structure and function of HIV-1 auxiliary regulatory protein Vpr: novel clues to
      drug design.
AB  - Vpr is a 96-amino acid auxiliary regulatory protein that is packaged in the HIV-1
      virion. It enhances the nuclear transport of the pre-integration complex, and
      regulates cell cycle, transcription and apoptosis. These biological activities
      suggest strongly that Vpr interacts with cellular biochemical pathways to
      regulate HIV-1 replication and pathogenesis. The karyophilic property of Vpr
      appears to be due to direct interaction of Vpr with nuclear transport factors and
      residents of the nuclear pore complex, whereas transcriptional effects of Vpr may
      be exerted through direct and indirect mechanisms. Cell cycle arrest at the G2/M
      checkpoint by Vpr is correlated with the hyperphosphorylation of Cdc2. The pro
      apoptotic activity of Vpr is dependent on the subtype of the HIV-1 isolate, and
      may be dramatically enhanced by a single L64P mutation. Mitochondria- and caspase
      dependent mechanisms appear to mediate Vpr-induced apoptosis. Recent evidence
      suggests that Vpr interacts with a cellular ubiquitination machinery and promotes
      degradation of Vpr mutants carrying the L64P mutation. Vpr interaction with the
      ubiquitination machinery may contribute to the regulation of the HIV-1 life cycle
      at various stages. NMR studies of Vpr have shown a Vpr monomer with three helical
      domains arranged in a twisted-U shape. However, Vpr most likely exists as a
      trimer in vivo. Structural/functional domains have been tentatively mapped for
      Vpr induction of apoptosis and for Vpr interaction with the ubiquitination
      machinery. Structural refinement of Vpr, specially by crystallography of the
      potential Vpr trimer, should help design therapeutic approaches to specifically
      target Vpr.

PMID- 15578978
TI  - The HIV-1 Tat protein: a multifaceted target for novel therapeutic opportunities.
AB  - Transcription of the integrated HIV-1 proviral genome is an essential step in the
      retrovirus life cycle and thus an appealing target for chemotherapeutic
      intervention to restrict retroviral replication. A fundamental role in this
      process is exerted by the viral protein Tat, a powerful transactivator of viral
      gene expression. This protein binds a structured RNA sequence at the 5'-ends of
      all nascent viral mRNAs and promotes transcription by mediating the recruitment
      to the viral promoter of cellular factors required for chromatin remodelling and
      transcriptional processivity. In addition to these transcriptional activities,
      Tat is released from the cells and enters neighbouring cells when present in the
      extracellular environment, a process that is possibly involved in HIV disease
      pathogenesis. Given its pleiotropic functions, the protein represents a highly
      appealing target for drug development. Here I will summarise the known molecular
      mechanisms by which Tat exerts its activities and review the currently available
      compounds that interfere with the process of transcriptional activation of the
      HIV-1 provirus.

PMID- 15578979
TI  - Controlling HIV-1 Rev function.
AB  - Although current therapies used in the treatment of HIV-1 infection have proven
      effective in reducing mortality due to the infection, the increase in drug
      resistant strains of the virus call for increased effort to explore and develop
      alternative treatment modalities. In this review, the various strategies to
      control HIV-1 replication through the disruption of Rev function are outlined. A
      wide range of methods have been developed including antisense DNA, ribozymes,
      decoy RNAs, transdominant proteins and suicide vectors targeted at disrupting Rev
      function. Although many of these methods have proven effective alone, it is hoped
      that a more robust antiviral response can be attained through combination of
      these strategies. As the methods of delivering these therapeutic agents matures
      through the development of lentiviral-based vectors, it is hoped that they will
      eventually reach the clinic where they may not only supplement the current
      treatment strategies but also provide resistance to those at high risk of
      infection or failing therapy.

PMID- 15578980
TI  - Recent advances in the understanding of HIV-1 Vpu accessory protein functions.
AB  - HIV-1 encodes a number of accessory proteins, which are not commonly found in
      other retroviruses. These proteins, which include Vif, Vpr, Vpu and Nef, act as
      multifunctional adapters capable of recruiting and modulating basic host cell
      processes to optimize wide-ranging aspects of viral replication. This review
      describes our current understanding of how the Vpu accessory protein functions to
      modulate HIV-1 particle release and CD4 receptor expression during HIV-1
      infection and underlines the potential opportunities afforded by this viral
      protein for therapeutic intervention.

PMID- 15578981
TI  - Functions of the HIV-1 Nef protein.
AB  - The Nef protein of the human immunodeficiency virus is as important for disease
      progression as it is perplexing in its number of target molecules and functions.
      In this chapter I will try to give an overview on the numerous functions of HIV
      from a molecular as well as functional point of view. Due to space restriction
      and for the sake of clarity I will not describe or list all the effects reported
      in the literature but rather concentrate on the most important aspects of Nef
      function.

PMID- 15578982
TI  - Therapeutic targeting of interactions between Nef and host cell proteins.
AB  - Nef is a viral pathogenicity factor that has an important role in disease
      progression associated with HIV infection. Yet, no antiviral drugs capable of
      inhibiting of Nef are available or in clinical trials today. In this review the
      challenges and potential involved in pharmaceutical targeting of Nef are
      discussed in light of current understanding of the molecular mechanisms of Nef
      action, with a special emphasis on effector functions of Nef that are mediated
      via SH3 domain-directed interactions with host cell proteins.

PMID- 15578983
TI  - Targeting the Nef induced increase of HIV infectivity.
AB  - Nef is a regulatory protein expressed exclusively by HIV-1/2 and SIV. It is
      critical for the optimal viral infectivity and for the destruction of the host
      immune system. This renders Nef a rather attractive therapeutic target. The most
      affordable point(s) of attack for effective anti-Nef therapeutic strategies can
      be individuated on the basis of a detailed knowledge of the mechanisms underlying
      the Nef induced enhancement of infectivity. However, the emerging picture still
      appears rather complex and not always coherent, so that additional, intensive
      endeavours in basic research are required for an effective exploitation of the
      Nef induced increase of infectivity as a therapeutic target.

PMID- 15578984
TI  - The impact of body mass index and type 2 diabetes on breast cancer: current
      therapeutic measures of prevention.
AB  - Epidemiological data have suggested a possible relationship between obesity,
      diabetes mellitus and cancer risk, particularly breast cancer. We set out to
      investigate the effect of body mass index and diabetes mellitus on the presence
      of breast cancer in the Apulian population. We selected 1,663 women affected with
      primary breast cancer and 4,702 control patients. All patients with breast cancer
      underwent surgical excision of the tumor and their tumors were histologically
      confirmed. The prevalence of type 2 diabetes (8%) in the women affected by breast
      cancer was significantly higher than in the control group (5%) (p<0.05). The
      majority of the diabetic women affected by breast cancer had a BMI value >25,
      both in premenopause and in postmenopause. With respect to BMI, the non-diabetic
      patients with breast cancer in postmenopause showed the same pattern as the
      diabetic ones. Instead, among the women in premenopause a higher percentage (55%)
      of patients with a BMI <24.9 was found (p<0.01). In the Apulian population, the
      presence of both type 2 diabetes and elevated values of BMI (that is in a
      condition of hyperinsulinemia) were found to enhance the frequency of breast
      cancer.

PMID- 15578985
TI  - New perspectives in the treatment of Cushing's syndrome.
AB  - Regardless of etiology, all cases of endogenous Cushing's syndrome are due to
      increased production of cortisol by the adrenal gland. Most are caused by
      adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Alternatively,
      the glucocorticoid excess may be due to adrenal neoplasia or to ectopic ACTH
      secreting tumors. Cushing's syndrome is characterized by endocrine and metabolic
      alterations such as truncal obesity, hypertension, weakness, amenorrhea,
      hyperglycemia, osteoporosis and depression. Unless treated, the disease is
      associated with high morbidity, and ultimately, mortality. Depending on the
      etiology of Cushing's syndrome two different treatment modalities are possible:
      reduction of pituitary ACTH production or reduction of adrenocortical cortisol
      secretion. In the absence of efficient drug therapy, transsphenoidal resection of
      the pituitary adenoma is the primary treatment of choice for the reduction of
      ACTH secretion. In the last years there was much progress in understanding the
      molecular mechanisms that control the function of the hypothalamic-pituitary
      adrenal axis. Thus, new insights made it possible to identify potential drug
      targets for the treatment of Cushing's syndrome. The present article reviews
      different drug targets and therapeutic options including drugs that control the
      central ACTH regulation, e.g. by modulating signaling pathways and
      transcriptional regulation of ACTH biosynthesis, corticotrophin releasing hormone
      (CRH) or glucocorticoid receptor antagonists, inhibitors of glucocorticoid
      synthesis, ketoconazole, somatostatin and dopamine analogs. Some of these
      substances might be useful for the treatment of Cushing's syndrome.

PMID- 15578986
TI  - Chemokine-chemokine receptor network in immune cell trafficking.
AB  - Chemokines play critical roles in leukocyte trafficking in normal and
      inflammatory conditions. The primary roles of chemokines are to activate
      integrins for leukocyte adherence on endothelial cells and to induce chemotaxis
      of leukocytes in tissue microenvironments. Specificity in leukocyte migration is
      regulated at multiple levels. First, it is achieved through differential tissue
      expression of chemokines and adhesion molecules. Second, it is achieved by
      limited and differential expression of chemokine receptors by leukocyte subsets.
      Third, combinatorial expression of multiple chemokine receptors and adhesion
      molecules makes leukocyte migration more specific. Homing of leukocytes into
      various tissue sites (e.g. inflamed skin, small intestine, mucosal tissues, T
      cell areas vs. B cell follicles) requires different chemokines and chemokine
      receptors. Furthermore, distinct immune responses and diseases (e.g. Th1 vs. Th2
      responses) involve different sets of chemokines and leukocyte subsets. This
      review examines the recent advances in research on chemokines and chemokine
      receptors in tissue-specific migration of immune cells, and discusses potential
      targets of intervention in chemokine-mediated leukocyte migration in normal and
      diseased conditions.

PMID- 15578987
TI  - Why do we need new gene therapy viral vectors? Characteristics, limitations and
      future perspectives of viral vector transduction.
AB  - The use of viruses to transduce genes of interest into mammalian cells has been
      extremely revolutionary, both in terms of laboratory research and for clinical
      purposes. This approach has allowed expression and over-expression of proteins of
      interest as well as the understanding of both virus life cycles and eukaryotic
      cell mechanisms. Beginning in the late eighties gene transduction has been
      applied to clinical trials but mainly restricted to cancer treatment and genetic
      diseases. More recently it has been proposed for the cure of infectious diseases
      (AIDS), vascular diseases and others (Alzheimer's and Parkinson's disease). Viral
      vectors have been progressively modified in order to increase their transduction
      efficiency and to reduce their toxicity, immunogenicity and inflammatory
      potential. In this respect, much has been done in the last few years. By adding
      genes belonging to other viral species to the vectors' DNA, scientists were able
      to re-direct their tissue-specificity or to control protein expression. More
      recently, in the attempt of overcoming the limitations of each viral species, so
      called chimeric viral vectors have been generated by combining favourable
      features of two or more different viruses into one. This review summarises the
      main characteristics of the most common viral vectors, including their
      advantages, limitations and possible future applications. It also briefly
      discusses development and evolution of chimeric vectors, treated in more details
      along this entire issue. Finally, we evaluate basic safety aspects, mandatory to
      consider for the clinical application of viral gene transduction.

PMID- 15578988
TI  - Retrotransposon-adenovirus hybrid vectors: efficient delivery and stable
      integration of transgenes via a two-stage mechanism.
AB  - It has long been recognized that the mechanisms mediating retrotransposition
      might be adapted for genomic integration and long-term expression of foreign
      genes. In particular, long interspersed nuclear elements (LINEs), an abundant
      class of retrotransposons that are the most active mobile genetic elements in the
      human genome, have been largely ignored as candidates for development as an
      integrating vector system because there has been no suitable method for
      efficiently introducing them into target cells. We have recently developed a LINE
      based retrotransposon-adenovirus hybrid vector, in which a helper-dependent
      adenovirus (HDAd) is utilized as the platform for delivery of a human L1 element
      and its linked heterologous transgene cassette into the host cell nuclei. While a
      major drawback to the use of HDAd vectors has been their lack of specific
      mechanisms to achieve permanent integration into the host genome, the inserted
      retrotransposon sequences overcome this limitation. The L1-HDAd hybrid thus
      represents a single vector capable of mediating long-term gene expression by a
      two-stage mechanism: in the first (adenovirus) stage, the helper-dependent
      adenovirus serves as a carrier for efficient delivery and transient expression of
      its encoded L1/transgene cassette, and in the second (retrotransposon) stage, the
      L1 retro-element and its associated transgene then permanently integrate into the
      genome of the adenovirus-transduced cells. We propose that this novel
      retrotransposon-adenovirus hybrid vector system will be useful both as a vehicle
      for efficient delivery and long-term stable transduction of therapeutic genes, as
      well as a tool to elucidate aspects of retrotransposon biology that have
      previously been difficult to study.

PMID- 15578989
TI  - Herpes simplex virus type 1 amplicons and their hybrid virus partners, EBV, AAV,
      and retrovirus.
AB  - HSV-1 amplicons can accommodate foreign DNA of any size up to 150 kbp. Genomic
      sequences as well as cDNA, large transcriptional regulatory sequences for cell
      type-specific expression, or multiple transgenes can be inserted in a modular
      fashion. HSV-1 amplicon vectors deliver DNA efficiently into the cell nucleus as
      an extrachromosomal, non-replicating circular concatenate, which is rapidly
      diluted, at least in dividing cells. Consequently, transgene expression is lost
      within days to weeks in dividing cells, but may be retained for months in non
      dividing cells. In contrast, vectors based on Epstein-Barr virus, adeno
      associated virus, or retroviruses can mediate long-term transgene expression, as
      vector DNA is retained by episomal replication or chromosomal integration. Hybrid
      amplicons use genetic elements from HSV-1 that allow replication and packaging of
      the vector DNA into HSV-1 virions, thereby conserving the large transgene
      capacity of HSV-1, and genetic elements from other viruses that confer genetic
      stability to the vector DNA within transduced cells. Additional strategies to
      sustain genetic material in infected cells include the incorporation of
      recombinases from different bacteriophages or transposable elements of the
      Tc1/mariner family in the amplicon vector. Moreover, modification of the HSV-1
      virion itself offers a myriad of possibilities to improve gene delivery by
      targeting specific cell populations or transporting foreign proteins, such as Cre
      recombinase or the adeno-associated virus Rep protein, which can control the fate
      and expression of the therapeutic transgene.

PMID- 15578990
TI  - Herpesvirus/retrovirus chimeric vectors.
AB  - Over the years, the design of HSV-1 based vectors has developed from different
      types of replicative-defective and replication-conditioned recombinant viruses to
      plasmid based amplicon vectors. More recently hybrid or chimeric vectors have
      incorporated desired elements of different viruses to increase the efficacy of
      gene delivery in vitro and in vivo. Amongst different systems,
      herpesvirus/retrovirus chimeras take advantage of the features of the HSV-1
      vectors to efficiently transduce large amounts of foreign genetic sequences,
      remaining episomal, to allow production of recombinant retrovirus vectors able to
      stably integrate into the cellular genome. This review will focus on three
      different groups of herpesvirus/retrovirus chimeric vectors aimed to: generate
      retrovirus particles in cells tranduced with HSV-1 amplicon vectors; express a
      limited set of retrovirus genes for vaccine purposes; and express
      herpesvirus/retrovirus chimeric proteins to study cellular targeting signal and
      improve their biological effect.

PMID- 15578991
TI  - Vaccinia viral/retroviral chimeric vectors.
AB  - Retroviral vectors have become important tools in gene therapy due to a number of
      desirable properties, including efficient gene delivery and stable genomic
      integration. Some shortcomings, however, still remain to be solved. Retroviral
      vectors cannot be grown to as high titers as for example adenoviruses or vaccinia
      viruses, they tend to be unstable and are sensitive to lysis by complement when
      transfused into patients. The search for more robust retroviral delivery systems
      has led to the development of hybrid viral vectors trying to combine the broadly
      estimated features of retroviral vectors with advantageous properties of a second
      viral vector system. Chimeric systems with retroviruses and adeno-alphavirus and
      herpesviruses have been reported. This review is dedicated to vaccinia virus, a
      widely used vector in molecular and cell biology, as a chimeric carrier for
      retroviral vector units. In the first poxviral/retroviral constructs, retroviral
      vector units integrated into a defective vaccinia vector, gave rise to
      transduction competent particles. Due to the high insertion capacity of the
      vaccinia system, also the packaging components could be inserted into the carrier
      virus resulting in a system that is independent of retroviral packaging cell
      lines. Moreover, since vaccinia is a cytoplasmic virus that does not recognize
      nuclear transcription and processing signals, retroviral vectors with introns and
      internal transcription stops could be constructed that transduce complex gene
      cassettes. The topic of this review is the vaccinia viral / retroviral vector
      system and possible applications to gene therapy.

PMID- 15578992
TI  - Strategies for retargeted gene delivery using vectors derived from lentiviruses.
AB  - With the development of the first viral vector systems 20 years ago [Mann et al.,
      1983; Watanabe and Temin, 1983] gene therapy strategies have come to the
      forefront of novel therapeutics [Cavazzana-Calvo et al., 2000]. A deeper
      understanding of vector biology and the molecular mechanisms of disease alongside
      tremendous advances in vector technology have significantly advanced the field of
      human gene therapy. Over the last few years several challenges needed to be
      overcome in order to bring gene therapy strategies closer to the clinic. These
      hurdles include the preparation of large amounts of stable, high titre vectors,
      minimising vector-related immunology and last but not least targeting infection
      and transgene expression to tissue or cells, which in many cases are not or only
      slowly dividing. Viral vectors are useful vehicles for the delivery of foreign
      genes into target cells, and retroviral vectors have been popular because of
      their ability to integrate into the host cell genome and maintain persistent gene
      expression. Moreover, lentiviruses, members of the retroviral family, have the
      ability to infect cells at both mitotic and post-mitotic stages of the cell cycle
      thus opening up the possibility to target non-dividing target cells and tissues.
      Human immunodeficiency virus (HIV) based vectors have been used in vitro and in
      vivo in a number of situations, however, safety concerns still exist, and
      therefore the development of vector systems based on primate as well as non
      primate lentiviruses is ongoing. Concomitantly with lentiviral vector design,
      much has been learned about the incorporation of heterologous env proteins on
      lentiviral cores in order to combine specific targeting properties of envelope
      glycoproteins with the biological properties of lentiviral vectors. In this
      review article we will give an overview over advantages lentiviral vector systems
      offer. We will then discuss the current state of our understanding of the
      structure and function of viral envelope glycoproteins and emerging targeting
      strategies based on retroviral and lentiviral vector systems.

PMID- 15578993
TI  - Towards multifunctional synthetic vectors.
AB  - Recent progress on the fronts of design, formulation and delivery with synthetic
      vectors has increased the potential of non-viral approaches to attain therapeutic
      applications. However, a number of hurdles remain to be cleared. On the one hand,
      we have the problem of producing and formulating stable, diffusible complexes and
      on the other hand, we have to face the fact that in vivo delivery is probably too
      complex and multifaceted to be achieved successfully with a single carrier
      molecule in most instances. This review concentrates on this latter aspect and
      the design of artificial multi-component vectors aimed at providing solutions to
      membrane crossing, endosomal escape and navigation through the nuclear pore. In
      many instances the solutions proposed have been inspired by natural mechanisms
      exploited by bacteria and viruses. However, entirely novel chemical approaches
      such as monomolecular DNA condensation via detergent dimerization, or endosome
      disruption by osmotic swelling, are also being investigated and developed. The
      combination of these naturally inspired and chemically-originated approaches is
      bringing us continually closer to the concept of constructing an artificial virus
      capable of delivering viable nucleic acid-based pharmaceuticals to defined cells
      in vivo. This review considers the most successful current solutions to the main
      biological barriers to gene delivery including appropriate DNA compaction, cell
      targeting and entry, vacuole escape, nuclear import and in vivo delivery. In the
      latter section, emphasis is placed on one of the most versatile non-viral vectors
      currently available, linear polyethylenimine.

PMID- 15578994
TI  - Tissue-specific targeting for cardiovascular gene transfer. Potential vectors and
      future challenges.
AB  - The introduction of genes to cardiovascular cells in vivo remains the major
      challenge for current gene therapy modalities. However, recent developments in
      retargeting adenoviral vectors are promising to improve transduction efficiency
      in the cardiovascular cells. After systemic application, most adenoviral vectors
      are trapped by the liver, hampering delivery to target cardiovascular tissues.
      Furthermore, a majority of vectors for vascular gene transfer utilizes strong
      heterologous viral promoters, such as CMV. A potential side effect related to the
      use of such vectors is the systemic organ toxicity resulting from unrestricted
      transgene expression. These vectors have the additional problem of being
      frequently shut-down in vivo. Therefore, both retargeting adenoviral vectors and
      the use of tissue-specific promoter-driven vectors offer an enhanced safety
      profile by reducing ectopic expression in vital organs including the liver and
      lung. However, the limiting factor for the use of tissue-specific promoters is
      the low-level of expression compared with their viral counterparts. Both the
      development of efficient and strong vectors using cell-specific regulatory
      elements and the production of therapeutic proteins at sufficient levels is
      urgently needed to inhibit vasculoproliferative disorders. This review will focus
      on some of the recent achievements in vector development relevant to the delivery
      of vascular gene therapies targeted to the vascular endothelium, smooth muscle
      cells and macrophages during arterial remodelling.

PMID- 15578995
TI  - Alternative gene therapy strategies for the repair of craniofacial bone defects.
AB  - Craniofacial anomalies, bone defects and cartilage lesions pose a difficult and
      challenging problem for both the doctor and for patients and their families.
      Conventional therapies focus on orthopaedic surgery, grafting with autogenous
      bone, allogenic bone grafts, or distraction osteogenesis. However, the efficacy
      of these techniques is limited by high cost, donor morbidity, scarcity of tissue
      resources, and alterations in volume [Marx & Morales, 1988]. On the basis of
      recent insights into the development, growth, and adaptation of bone, together
      with the significant advances in recombinant DNA technology, gene therapy is
      increasingly becoming recognised as an alternative technique for augmenting and
      promoting bone regeneration in vivo. It can be applied in craniofacial skeletal
      tissues by transferring genes encoding for specific growth factors such as BMPs
      in osteoblasts, chondrocytes or progenitor cells for the purpose of enhancing
      protein production [Scaduto & Lieberman, 1999]. It can be performed by either
      direct administration of gene delivery vectors, or by transplantation of
      genetically modified cells. This review will focus on recent advances in
      molecular mechanisms of bone formation, and development in various viral and non
      viral vectors for direct in vivo therapeutic gene transfer and genetically
      engineered cells ex vivo therapy.

PMID- 15578996
TI  - Potential genetic therapies for acute lung injury.
AB  - Acute lung injury (ALI) is a common, highly lethal acquired disorder that affects
      over one hundred thousand people each year and for which there are no specific
      therapies. Extensive investigations in experimental models and humans with ALI
      have identified several maladaptive host responses and dysregulated protein
      systems that offer therapeutic opportunities for genetic intervention. Several
      lines of evidence suggest that gene transfer can be used to deliver protective
      proteins that improve alveolar epithelial and/or endothelial cell function or
      immunomodulators that augment lung defense mechanisms and speed clearance of
      infection. In many instances, gene transfer is the only avenue for producing
      localized expression of these pharmaceuticals. This article reviews recent
      translational, animal-based studies that tested the use of gene and cell based
      therapies to ameliorate or prevent ALI. The lack of effective therapies for ALI
      and the approachability of the lung for local gene transfer suggest that ALI is a
      unique example of an acute disease process that is suitable for gene therapy.

PMID- 15578997
TI  - Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.
AB  - Ziconotide (PRIALT) is a neuroactive peptide in the final stages of clinical
      development as a novel non-opioid treatment for severe chronic pain. It is the
      synthetic equivalent of omega-MVIIA, a component of the venom of the marine
      snail, Conus magus. The mechanism of action underlying ziconotide's therapeutic
      profile derives from its potent and selective blockade of neuronal N-type voltage
      sensitive calcium channels (N-VSCCs). Direct blockade of N-VSCCs inhibits the
      activity of a subset of neurons, including pain-sensing primary nociceptors. This
      mechanism of action distinguishes ziconotide from all other analgesics, including
      opioid analgesics. In fact, ziconotide is potently anti-nociceptive in animal
      models of pain in which morphine exhibits poor anti-nociceptive activity.
      Moreover, in contrast to opiates, tolerance to ziconotide is not observed.
      Clinical studies of ziconotide in more than 2,000 patients reveal important
      correlations to ziconotide's non-clinical pharmacology. For example, ziconotide
      provides significant pain relief to severe chronic pain sufferers who have failed
      to obtain relief from opiate therapy and no evidence of tolerance to ziconotide
      is seen in these patients. Contingent on regulatory approval, ziconotide will be
      the first in a new class of neurological drugs: the N-type calcium channel
      blockers, or NCCBs. Its novel mechanism of action as a non-opioid analgesic
      suggests ziconotide has the potential to play a valuable role in treatment
      regimens for severe chronic pain. If approved for clinical use, ziconotide will
      further validate the neuroactive venom peptides as a source of new and useful
      medicines.

PMID- 15578998
TI  - Potassium channel blockade by the sea anemone toxin ShK for the treatment of
      multiple sclerosis and other autoimmune diseases.
AB  - Expression of the two lymphocyte potassium channels, the voltage-gated channel
      Kv1.3 and the calcium activated channel IKCa1, changes during differentiation of
      human T cells. While IKCa1 is the functionally dominant channel in naive and
      "early" memory T cells, Kv1.3 is crucial for the activation of terminally
      differentiated effector memory (TEM) T cells. Because of the involvement of TEM
      cells in autoimmune processes, Kv1.3 is regarded as a promising target for the
      treatment of T-cell mediated autoimmune diseases such as multiple sclerosis and
      the prevention of chronic transplant rejection. ShK, a 35-residue polypeptide
      toxin from the sea anemone, Stichodactyla helianthus, blocks Kv1.3 at low
      picomolar concentrations. ShK adopts a central helix-kink-helix fold, and alanine
      scanning and other mutagenesis studies have defined its channel-binding surface.
      Models have been developed of how this toxin effects K+-channel blockade and how
      its docking configuration might differ in ShK-Dap22, which contains a single side
      chain substitution that confers specificity for Kv1.3 blockade. ShK, ShK-Dap22
      and the Kv1.3 blocking scorpion toxin kaliotoxin have been shown to prevent and
      treat experimental autoimmune encephalomyelitis in rats, a model for multiple
      sclerosis. A fluoresceinated analog of ShK, ShK-F6CA, has been developed, which
      allows the detection of activated TEM cells in human and animal blood samples by
      flow cytometry and the visualization of Kv1.3 channel distribution in living
      cells. ShK and its analogs are currently undergoing further evaluation as leads
      in the development of new biopharmaceuticals for the treatment of multiple
      sclerosis and other T-cell mediated autoimmune disorders.

PMID- 15578999
TI  - Sodium channel toxins--receptor targeting and therapeutic potential.
AB  - Sodium channels underlie propagated electrical signalling in most excitable
      cells, including neurons and the myocytes of skeletal muscle and heart. These
      proteins are targeted by a variety of current therapeutic drugs to combat such
      maladies as pain, myotonias, epilepsies and cardiac arrhythmias. Typically, these
      problems are associated with overactivity of sodium channels leading to
      hyperexcitability in the relevant tissue. More than ten distinct but closely
      related molecular isoforms of mammalian sodium channel are now known to be
      specifically expressed in different cell types and tissues. Therapeutic
      attenuation of sodium channel activity must be effected with great precision in
      both targeting and the degree of reduction in channel activity if a malfunction
      is to be corrected without introducing deleterious or even catastrophic side
      effects. Numerous natural toxins have evolved to target sodium channels, either
      by blocking current through the pore or by modifying channel gating. Among the
      well studied toxins, the peptide conotoxins from cone snail venoms show a
      remarkable ability to discriminate among closely related forms of sodium channel,
      as well as exhibiting a variety of modes of action. Here, we examine the
      molecular basis of action of different Na channel targeted conotoxins and explore
      their potential as models for the future design of more specifically targeted
      drugs.

PMID- 15579000
TI  - Dendrotoxins: structure-activity relationships and effects on potassium ion
      channels.
AB  - Dendrotoxins are small proteins isolated from mamba (Dendroaspis) snakes. The
      original dendrotoxin was found in venom of the Eastern green mamba, Dendroaspis
      angusticeps, and related proteins were subsequently found in other mamba venoms.
      The dendrotoxins contain 57-60 amino acid residues cross-linked by three
      disulphide bridges, and they are homologous to Kunitz-type serine protease
      inhibitors, such as aprotinin (BPTI). The dendrotoxins have little or no anti
      protease activity, but they block particular subtypes of voltage-dependent
      potassium channels of the Kv1 subfamily in neurones. Alpha-dendrotoxin from green
      mamba Dendroaspis angusticeps and toxin I from the black mamba Dendroaspis
      polylepis block cloned Kv1.1, Kv1.2 and Kv1.6 channels in the low nanomolar
      range; toxin K, also from the black mamba Dendroaspis polylepis, preferentially
      blocks Kv1.1 channels and is active at picomolar concentrations. Structural
      modifications and mutations to dendrotoxins have helped to define the molecular
      recognition properties of different types of K+ channels, although more work is
      needed to characterise the chemical features of the toxins that underlie their
      selectivity and potency at particular subtypes of channels. Dendrotoxins have
      been useful markers of subtypes of K+ channels in vivo, and dendrotoxins have
      become widely used as probes for studying the function of K+ channels in
      physiology and pathophysiology. With some pathological conditions being
      associated with voltage-gated K+ channels, analogues of dendrotoxins might have
      therapeutic potential.

PMID- 15579001
TI  - Conantokins: peptide antagonists of NMDA receptors.
AB  - Conantokins are small peptides (17-27 amino acids) found in the venoms of cone
      snails (Conus sp.) that inhibit the activity of N-methyl-D-aspartate (NMDA)
      receptors. Unlike most of the peptides characterized from cone snail venom that
      contain multiple disulfide bridges, conantokins are linear peptides that possess
      a high degree of alpha-helicity in the presence of divalent cations, and contain
      gamma-carboxyglutamic acid residues. Four naturally occurring conantokins have
      been identified and characterized to date, conantokin-G, conantokin-T, conantokin
      R, and conantokin-L. The most extensively characterized, conantokin-G, is
      selective for subtypes of NMDA receptors containing the NR2B subunit. The
      conantokins have been synthesized and characterized in a number of animal models
      of human pathologies including pain, convulsive disorders, stroke, and
      Parkinson's disease. The potential pharmacological selectivity of the
      conantokins, coupled with their efficacy in preclinical models of disease and
      favorable safety profiles indicate that these peptides represent both novel
      probes for NMDA receptor function as well as an important class of compounds for
      continued investigation as human therapeutics.

PMID- 15579002
TI  - Botulinum toxin: a successful therapeutic protein.
AB  - Botulinum toxin serotype A has proven to be a successful and valuable therapeutic
      protein when dosage, frequency of treatment and variety of treated clinical
      conditions are considered. This modern therapeutic protein was predicted by
      Justinus Kerner, a 19th century German physician, who provided the first detailed
      clinical description of botulism and its association with faulty sausage
      production. Kerner was preceded by Paracelsus, who described the duality of a
      drug as "only the dose makes a remedy poisonous". This concept is well known to
      modern medicinal chemists, pharmacologists and clinicians worldwide. Because
      botulinum toxin is an enzyme and specifically delivered to its target
      cell/neuron, exceedingly small doses are needed to exert its pharmacological
      effect. Botulinum toxin therapy is successful because of the local administration
      of nanogram quantities of this highly selective and long-lasting (months)
      therapeutic effect, which leads to symptomatic relief of numerous disease
      conditions. These minute therapeutic doses are dramatically lower than the doses
      needed to cause systemic disease (e.g. botulism). This review will focus on the
      current understanding of the mechanism of action of botulinum neurotoxins and the
      pharmacology of the various approved-marketed products and the direction of
      future research.

PMID- 15579003
TI  - Free energy of ligand binding to protein: evaluation of the contribution of water
      molecules by computational methods.
AB  - One of the more challenging issues in medicinal chemistry is the computation of
      the free energy of ligand binding to macromolecular targets. This allows for the
      screening of libraries of chemicals for fast and inexpensive identification of
      lead compounds. Many attempts have been made and several algorithms have been
      developed for this purpose. Whereas enthalpic contributions are evaluated using
      methods and equations for which there is a reasonable consensus among
      researchers, the entropic contribution is evaluated using very different, and, in
      some cases, very approximate methods, or it is entirely ignored. Entropic
      contributions are of primary importance in the formation of many ligand-protein
      complexes, as well as in protein folding. The hydrophobic interaction, associated
      with the release of water molecules from the protein active site and the ligand,
      plays a significant role in complex formation, predominantly contributing to the
      total entropy change and, in some cases, to the total free energy of binding.
      There are distinct approaches for the evaluation of the contribution of water
      molecules to the free energy of binding based on Newtonian mechanics force
      fields, multi-parameter empirical scoring functions and experimental force
      fields. This review describes these methods -- discussing both their advantages
      and limitations. Particular emphasis will be placed on HINT (Hydropatic
      INTeractions), a "natural" force field that takes into account in a unified way
      enthalpic and entropic contributions of all interacting atoms in protein-ligand
      complexes, including released and structured water molecules. As a case-study,
      the contribution of water molecules to the binding free energy of HIV-1 protease
      inhibitors is evaluated.

PMID- 15579004
TI  - Recent advances in chemical genomics.
AB  - Chemical genomics, which utilizes specially designed small chemical compounds
      early in the discovery phase of new drugs to explore the life science at various
      levels, can address biological questions that are not amenable to genetic
      manipulation or functional genomics/proteomics approaches. Following the
      development of HT phenotypic assays and DNA expression analysis, the integration
      of cell-based assays with activity / affinity-based approaches allows us to
      interrogate the cells by analyzing phenotypic alterations, changes of transcript
      signature or detecting the differences in protein expression levels. Furthermore,
      activity / affinity-based techniques directly provide a druggable subset of gene
      products, which interact with small molecules, greatly reducing the complexity of
      analyzing the proteome. In this paper, we give an account of the recent advances
      (approaches and strategies) in the field of chemical genomics, and discuss how
      these approaches enable the investigator to obtain a novel therapeutically
      relevant target as well as drug candidates acting on them in a target-specific
      manner. This novel post-genomic discovery strategy, where target identification/
      validation is carried out by interactions with small molecules, could
      significantly reduce the time-scale for early drug discovery, and increase the
      success rate of finding novel, druggable targets, as well as more specific drug
      candidates.

PMID- 15579005
TI  - Novel insights and therapeutical applications in the field of inhibitors of COX
      2.
AB  - The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their
      function, localisation and regulation has initiated the development of COX-2
      selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of
      inflammation has been detected in the early 1990s, the involvement of recently
      detected spinal COX-2 has led to new insights into mechanisms of pain and may
      explain analgesic and antipyretic properties of COX-2 selective inhibitors. The
      coxibs rofecoxib and celecoxib have been introduced into therapy and seem to
      offer some advantages over the classical non-selective NSAIDs. The search for new
      COX-2 inhibitors is going on, the development of etoricoxib and lumiracoxib is a
      step ahead concerning efficacy, tolerability and safety. Until today COX-2
      selective inhibitors have found their place in therapy of arthritis,
      osteoarthritis, dysmenorrhea and acute pain. A new paradigm in pain therapy seems
      to justify their use in perioperative settings in a preemptive or multimodal
      therapeutical strategy. In the future COX-2 selective inhibitors as opioid
      sparing agents could become an important tool in pain therapy. Even a
      therapeutical benefit of COX-2 selective inhibitors in the treatment of
      Alzheimer's Disease or in the prevention or treatment of colorectal or prostate
      cancer is presently intensely investigated. Recently some authors reported on COX
      3, a splicing variant of COX-1. If COX-3 really represents the target for
      acetaminophen must be called into question.

PMID- 15579006
TI  - ET-18-OCH3 (edelfosine): a selective antitumour lipid targeting apoptosis through
      intracellular activation of Fas/CD95 death receptor.
AB  - Synthetic ether-linked analogues of phosphatidylcholine and
      lysophosphatidylcholine, collectively named as antitumour lipids (ATLs), were
      initially synthesized in the late 60s, but have attracted a renewed interest
      since the finding that the ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3
      phosphocholine (ET-18-OCH3, edelfosine), a synthetic analogue of 2
      lysophosphatidylcholine considered the ATL prototype, induces a selective
      apoptotic response in tumour cells, sparing normal cells. Unlike most
      chemotherapeutic agents currently used, ET-18-OCH3 does not interact with DNA,
      but act at the cell membrane, and thereby its effects seem to be independent of
      the proliferative state of target cells. Each part of the molecular structure of
      ET-18-OCH3 is important for its optimal proapoptotic activity. Recent progress
      has unveiled the molecular mechanism underlying the apoptotic action of ET-18
      OCH3, involving membrane rafts and Fas/CD95 death receptor, and has led to the
      proposal of a two-step model for the ET-18-OCH3 selective action on cancer cells,
      namely: a) ET-18-OCH3 uptake into the tumour cell, but not in normal cells; b)
      intracellular activation of Fas/CD95 through its translocation and capping into
      membrane rafts. ET-18-OCH3 constitutes the first antitumour drug acting through
      the intracellular activation of the Fas/CD95 death receptor. Computational
      docking studies have allowed us to propose a molecular model for the putative
      interaction of ET-18-OCH3 with the intracellular Fas/CD95 death domain. This
      novel mechanism of action represents a new way to target tumour cells in cancer
      chemotherapy and can be of interest as a new framework in designing novel and
      more selective proapoptotic antitumour drugs.

PMID- 15579007
TI  - Current perspectives on the therapeutic utility of VR1 antagonists.
AB  - This review gives a brief overview of the expression patterns, molecular
      pharmacology and physiological roles of the vanilloid receptor 1 (VR1).
      Particular emphasis is given to the therapeutic utility of VR1 modulators. Small
      molecule agonists of VR1, including capsaicin and RTX, are currently utilized for
      a number of clinical syndromes, including intractable neuropathic pain, spinal
      detrusor hyperreflexia, and bladder hypersensitivity; however, antagonists of VR1
      have yet to reach the clinic. While the classic VR1 antagonist, capsazepine has
      proven a useful tool for unraveling the molecular pharmacology of VR1, in vivo
      studies with this compound have had limited success due to poor pharmacokinetic
      properties and species selectivity issues. With the cloning of VR1 in 1997, the
      pharmaceutical community has been provided a molecular target for high throughput
      screening and small molecule lead discovery and optimization. As a result,
      resurgence in the interest of VR1 antagonists has given way to many new
      pharmacological agents that may provide better tools to probe VR1 physiology, and
      ultimately yield promising therapeutic agents.

PMID- 15579008
TI  - Proteomics: state of the art and its application in cardiovascular research.
AB  - The cellular and molecular mechanisms underlying cardiovascular dysfunctions are
      widely unknown. Basically, pathological changes in the cardiovascular system
      arise from protein alterations. Proteomics comprises a set of tools for the large
      scale study of gene expression at the protein level thereby allowing for the
      identification of protein alterations responsible for the development and the
      pathological outcome of diseases including those of the cardiovascular system. In
      principle these alterations include those of suitable candidates for drug targets
      and disease biomarkers as well as therapeutic proteins/peptides. Since gene
      therapy depends on the function of a therapeutic protein encoded by a
      "therapeutic" gene proteomic analyses also provide the basis for the design and
      application of gene therapies. Proteomic technologies allow to identify not only
      proteins but also the nature of their posttranslational modifications thus
      enabling the elucidation of signal transduction pathways and their deregulation
      under pathological conditions. The linkage of information about proteome changes
      with functional consequences lead to the development of functional proteomic
      studies. Functional proteomic analyses will particularly help to better
      understand the relations between proteome changes and cardiovascular
      dysfunctions. The storage and administration of experimental data obtained by the
      application of proteomic analyses is supported by species- and tissue-specific
      protein databases and specific software. Publications in this field are reviewed
      in this paper.

PMID- 15579009
TI  - Effect of the antifibrillatory compound tedisamil (KC-8857) on transmembrane
      currents in mammalian ventricular myocytes.
AB  - The cellular mechanism of action of tedisamil (KC-8857) (TED), a novel
      antiarrhythmic/antifibrillatory compound, was studied on transmembrane currents
      in guinea pig, rabbit and dog ventricular myocytes by applying the patch-clamp
      and the conventional microelectrode technique. In guinea pig myocytes the rapid
      component of the delayed rectifier potassium current (IKr) was largely diminished
      by 1 microM TED (from 0.88+/-0.17 to 0.23+/-0.07 pA/pF, n=5, p<0.05), while its
      slow component (IKs) was reduced only by 5 microM TED (from 8.1+/-0.3 to 4.23+/
      0.07 pA/pF, n=5, p<0.05). TED did not significantly change the IKr and IKs
      kinetics. In rabbit myocytes 1 microM TED decreased the amplitude of the
      transient outward current (I(to)) from 20.3+/-4.9 to 13.9+/-2.8 pA/pF (n=5,
      p<0.05), accelerated its fast inactivation time constant from 8.3+/-0.6 to 3.5+/
      0.5 ms (n=5, p<0.05) and reduced the ATP-activated potassium current (IKATP) from
      38.2+/-11.8 to 18.4+/-4.7 pA/pF (activator: 50 microM cromakalim; n=5, p<0.05).
      In dog myocytes 2 microM TED blocked the fast sodium current (INa) with rapid
      onset and moderately slow offset kinetics, while the inward rectifier potassium
      (IK1), the inward calcium (ICa) and even the I(to) currents were not affected by
      TED in concentration as high as 10 microM. The differences in I(to)
      responsiveness between dog and rabbit are probably due to the different alpha
      subunits of I(to) in these species. It is concluded that inhibition of several
      transmembrane currents, including IKr, IKs, I(to), IKATP and even INa, can
      contribute to the high antiarrhythmic/antifibrillatory potency of TED, underlying
      predominant Class III combined with I A/B type antiarrhythmic characteristics.

PMID- 15579010
TI  - Sequence variants of the ligand-binding domain of the glucocorticoid receptor
      gene and their functional consequences on the three-dimensional protein
      structure.
AB  - In recent years several mutations and sequence polymorphisms of the
      glucocorticoid receptor gene have been described. The majority of mutations have
      been found in patients with a rare endocrinological abnormality, the
      glucocorticoid resistance syndrome. In addition, some sequence polymorphisms have
      been considered to contribute to various diseases, but unambiguous correlations
      have not been established yet. Here we present the results of an in silico study,
      which revealed previously undescribed sequence variants of the glucocorticoid
      receptor gene. Although the three-dimensional structure of the DNA-binding domain
      of the glucocorticoid receptor has been known for several years, the crystal
      structure of the ligand-binding domain of the receptor has been published only
      recently. Using a comparative protein modelling, we analysed the structural
      relevance of known mutations as well as novel sequence variants discovered by our
      in silico approach in the ligand-binding domain of the glucocorticoid receptor.
      We conclude that comparative protein modelling of these mutant receptor variants
      offers a useful means to predict the functional consequences of amino acid
      replacements and to correlate structural abnormalities with clinical findings.

PMID- 15579011
TI  - Furocoumarins in medicinal chemistry. Synthesis, natural occurrence and
      biological activity.
AB  - The scope of this review encompasses the importance of furocoumarins and the most
      important developments in this field that have been made in recent years, with
      particular emphasis placed on the aspects related to medicinal chemistry. A
      concise and exhaustive overview is given regarding the methods used for the
      synthesis of these compounds, new furocoumarins isolated from natural sources,
      and the most significant biological properties associated with these molecules.
      The section describing the synthetic methods is organized on the basis of the key
      step used for the formation of the two different oxygenated rings. In this
      respect there are three possibilities: (i) formation of the furan ring onto the
      coumarin, (ii) formation of the pyrone ring onto the benzofuran and (iii) the
      simultaneous formation of both oxygenated rings onto a benzene unit. The most
      recent preparative approaches are discussed along with modifications or
      improvements to methods that, though not particularly new, are still commonly
      used. The recently discovered natural furocoumarins are focused and presented in
      tables that provide information about its structure and source. The discussion of
      the biological importance of furocoumarins mainly focuses on their more relevant
      applications in photochemotherapy, but also provides examples of their
      versatility in a range of applications in the fields of biology and pharmacology.

PMID- 15579012
TI  - Recent advances in design, synthesis and biological activity of
      aminoalkylsulfonates and sulfonamidopeptides.
AB  - The replacement of peptide bond is an important segment in the synthesis of
      peptidomimetics, because this modification may result in the preparation of
      biologically active analogues with improved properties, especially regarding
      bioavailability and metabolical stability. The introduction of sulfonamide group
      increases polarity of a molecule and the hydrogen-bond donor properties as a
      sulfonamide N-H is more acidic (pKa=11-12) than carboxamide. Furthermore, due to
      geometry of sulfur atom the sulfonamido bond shows structural similarity to the
      tetrahedral transition state present as an intermediate in the enzymatic
      hydrolysis of an amide bond thus making these compounds candidates in the
      development of new drugs. Recent advances in the synthesis of building blocks for
      sulfonamidopeptides, such as alpha or beta- substituted aminoalkylsulfonates and
      efficient methods for the formation of sulfonamide bond have enabled the
      preparation of large number of oligomers with potential applications on various
      fields. These methods have been applied for the synthesis of
      oligopeptidosulfonamides, catalysts, receptor molecules and enzyme inhibitors.
      This article deals with physicochemical properties of sulfonamides, synthesis of
      aminoalkylsulfonates and sulfonamidopeptides, and the biological activity of
      these compounds.

PMID- 15579013
TI  - Can PPAR gamma ligands be used in cancer therapy?
AB  - The role of peroxisome-proliferator activated receptor (PPAR)gamma in tumor
      growth inhibition has been extensively studied during last seven years but still
      remains debated. Many in vitro and xenograft studies have demonstrated that
      PPARgamma ligands are anti-tumorigenic due to anti-proliferative, pro
      differentiation and anti-angiogenic effects. In animal models, PPARgamma ligands
      have shown preventive effects against chemical carcinogenesis. On the other hand,
      evidences are accumulating against the possible use of this ligand activated
      nuclear receptor in molecular targeting for cancer therapy. The growth inhibitory
      effects of certain PPARgamma ligands have recently been shown to be independent
      of PPARgamma-activation. Studies have also come up with results indicating the
      growth promoting effects of PPARgamma-activation, particularly in certain animal
      models genetically predisposed to cancer development. Loss-of-function mutations
      of PPARgamma in tumors and increased susceptibility of PPARgamma heterozygote
      knockout mice to carcinogenesis suggested a tumor-suppressing role of PPARgamma.
      However, recent findings do not support PPARgamma as a tumor suppressor gene.
      Although initial clinical trials with PPARgamma ligand troglitazone reported
      promising results in liposarcoma and prostate cancers, recent studies failed to
      show the expected therapeutic values in advanced colorectal and breast cancers.
      In this review, we have addressed these controversies on potential use of
      PPARgamma ligands in cancer therapy.

PMID- 15579014
TI  - Cytoprotection and immunomodulation in cancer therapy.
AB  - Bioprospecting and natural products drug development for cancer treatment has
      become an important area. Most of the cancer chemotherapeutic agents are
      associated with toxicity towards normal cells and tissues. Optimal dosing of
      cancer chemotherapeutic agents is often limited because of severe non
      myelosuppressive and myelosuppressive toxicities. It is a continuing challenge to
      design therapy that is safer, effective and selective. Cytoprotective agents
      offer opportunities to reduce treatment related toxicity of anticancer therapy
      without diminution of efficacy. None of the available agents satisfy criteria for
      an ideal cytoprotection. This has stimulated research for discovering natural
      resources with immunomodulatory and cytoprotective activities. This article
      describes chemical agents presently employed in clinical practice and reviews
      ethnopharmacological agents reported to have chemoprotective, radioprotective,
      immunomodulating, adaptogenic and antitumour activities.

PMID- 15579015
TI  - Multiple targeting by the antitumor drug tamoxifen: a structure-activity study.
AB  - Tamoxifen is a well-known antiestrogen used for the hormonotherapy of estrogen
      receptor positive breast cancer. In addition to its high affinity binding to the
      estrogen receptor (ER), tamoxifen binds with comparable affinity to the
      microsomal antiestrogen binding site (AEBS), and inhibits with a micromolar
      efficiency, protein kinase C (PKC), calmodulin (CaM)-dependent enzymes and Acyl
      CoenzymeA: Cholesterol Acyl Transferase (ACAT). Each of these tamoxifen targets
      might explain the genomic as well as non-genomic effects of tamoxifen. In this
      review, we will report current knowledge about the structural features of
      tamoxifen involved in this multiple targeting. These data provide a useful guide
      for the conception of selective ligands of ERs, AEBS, PKC, CaM or ACAT based on
      the chemical structure of tamoxifen.

PMID- 15579016
TI  - Biological targets of antitumor indolocarbazoles bearing a sugar moiety.
AB  - Natural and synthetic indolocarbazole compounds have triggered considerable
      interest since the discovery in 1986 of the inhibitory properties of
      staurosporine toward protein kinase C (PKC). Later, it has been shown that
      indolocarbazole compounds may inhibit various kinases, such as cyclin dependent
      kinases and/or topoisomerase I, someones behave only as DNA intercalators. In
      this review are presented various indolocarbazole compounds bearing a sugar
      moiety and their biological targets. The relevance of these targets to develop
      indolocarbazole compounds as potential antitumor agents is discussed.

PMID- 15579017
TI  - Aromatase inhibitors: a new paradigm in breast cancer treatment.
AB  - Microsomal cytochrome P450 (CYP 450) enzyme aromatase belongs to CYP 19 super
      family. It is involved in the conversion of androgens to estrogens. In
      postmenopausal women the main sites of aromatisation are skin, adipose tissue and
      breast. Aromatase localized in breast tumor produces sufficient estrogen for its
      proliferation. Hence it is an important target for the treatment of hormone
      dependent breast cancer in postmenopausal women. There are mainly two types of
      aromatase inhibitors, one is steroidal another is nonsteroidal type. The first
      and second generation aromatase inhibitors encounter the undesirable drug- drug
      interactions besides being not very specific and plagued with pharmacokinetic
      problems. Third generation aromatase inhibitors developed recently are more
      potent and specific with a greater capacity to annihilate circulating estrogen
      levels. These agents have satisfactory pharmacokinetic profiles and are devoid of
      major drug-drug interactions. Third generation aromatase inhibitors became drugs
      of choice for both first and second line treatment of advanced breast cancer.
      Aromatase inhibitors can also be used for neoadjuvant therapy of breast cancer in
      which they have achieved better therapeutic efficacy than tamoxifen. Early
      results of ATAC (Armidex Tamoxifen Alone or Combination) trial suggest that
      anastrozole is superior to tamoxifen in adjuvant setting for disease free
      survival, particularly in receptor positive patients, and in reducing the
      incidence of contralateral breast cancer. Therapeutic potential of aromatase
      inhibitors stretches beyond the postmenopausal breast cancer treatment as they
      also play a role in the treatment of estrogen dependent benign and malignant
      conditions such as gynaecomastia, prostate cancer, fibroadenomata and the
      induction of ovulation. By virtue of their ability to reduce estrogen levels they
      pose problems like demineralization of bone, hot flushes and anti-implantation
      effects.

PMID- 15579018
TI  - Role of the non-neuronal human cholinergic system in lung cancer and
      mesothelioma: possibility of new therapeutic strategies.
AB  - Acetylcholine (Ach), one of the most important examples of a neurotransmitter,
      represents a phylogenetically old molecule, widely distributed from bacteria to
      humans. The finding that neuronal Ach receptors (nAChRs) are present in non
      neuronal cells raised some interesting issues related to their specific activity.
      In humans, different studies have showed that many lung cancer cells expressed
      nAchRs and that low concentrations of nicotine blocked the induction of apoptosis
      in these cells. A recent study presents data that SCLC express a cholinergic
      autocrine loop that can regulate cell growth. Such work demonstrates that SCLC
      cells have a cholinergic phenotype and that ACh exerts as an autocrine growth
      factor in human lung tumors. Recently it has been shown that human malignant
      pleural mesothelioma express a cholinergic system, involved in cell growth
      regulation. Hence, mesothelioma cell growth as well as normal mesothelial cells
      growth is modulated by the cholinergic system in which agonists (i.e. nicotine)
      has a proliferative effect and antagonists (i.e. curare) has an inhibitory
      effect. Furthermore apoptosis mechanisms in mesothelioma cells are under the
      control of the cholinergic system (nicotine antiapoptotic via induction of NF
      kappaB complexes and phosphorilation of Bad at Serine(112), curare proapoptotic
      via G(0)-G(1) arrest p21(waf-1)-dependent, but p53-independent). The involvement
      of the non-neuronal cholinergic system in lung cancer and mesothelioma appears
      reasonable and open up new therapeutic strategies.

PMID- 15579019
TI  - An update on the systemic therapy of malignant salivary gland cancers: role of
      chemotherapy and molecular targeted agents.
AB  - Salivary gland cancers are a rare malignancy accounting for less than 1% of all
      cancers and 3-6% of cancers of the head and neck region. The classification of
      salivary gland tumors is traditionally based on morphology and the different
      subtypes exhibit various clinical behaviors. The low grade and biologically
      indolent cell types include the adenoid cystic, acinic cell and adenocarcinoma
      while the salivary duct, squamous and mucoepidermoid are more active and high
      grade. The initial management of salivary gland malignancies is to assess
      resectability and possible adjuvant radiation therapy. Those with locoregional
      recurrence or metastatic disease are treated with systemic therapy. Numerous
      studies with small sample sizes have assessed the activity of different cytotoxic
      agents. Both single agent and combination chemotherapy have been used for the
      treatment of this disease. For these agents, the response rates are generally
      modest with objective response rates ranging from 15-50%. Duration of response is
      typically cited in the range of 6-9 months. Clinicopathological data have
      demonstrated correlations between poor clinical outcomes and the expression of
      molecular markers such as mutated p53 protein and vascular endothelial growth
      factor (VEGF) in salivary gland cancers. Recent studies have also evaluated the
      epidermal growth factor receptor family including erbB1/EGFR and erbB2/HER2 as
      potential therapeutic targets. While the prognostic significance of EGFR
      overexpression has not been well defined, overexpression of the HER2 oncoprotein
      has been associated with biological aggressiveness and poor prognosis in most
      series. Given the suboptimal response rates, duration of response, and toxicity
      of conventional chemotherapy, a better understanding of the biology of salivary
      gland malignancies will lead to improved prognostication and treatment. With the
      emergence of molecular targeted therapy, these tumors become an optimal candidate
      for trials of investigational drugs and established drugs for new indications.

PMID- 15579020
TI  - The chemical dynamics of NO and reactive nitrogen oxides: a practical guide.
AB  - Nitric oxide has emerged as one of the most important and diverse players in
      physiology. This small diatomic radical stunned researchers because of its
      existence and unique biological properties in human physiology. Over the last two
      decades it was found that NO often has fickle behavior in pathophysiological
      mechanisms. Where benefiting the host in one case yet inducing and augmenting
      injury in another. This has lead to confusion in is NO good or bad? Much of the
      answers to this dichotomy lies in the chemistry of NO and its related nitrogen
      oxide species. To help understand the complex chemistry with perspective to
      biology, a discussion on the chemical biology of NO is useful. The chemical
      biology defines the relevant chemical reaction of NO and nitrogen monoxide in the
      context of the biological conditions. We discuss in this article the chemistry of
      nitrogen oxide with different types of biological motifs. Reaction of NO with
      metal complexes and radicals require low concentration, where formation of
      reactive nitrogen oxide species require considerably higher amounts and generally
      are isolated to specific microenvironments in vivo. Though many reactive nitrogen
      oxide species are formed from chemical reactions with NO, there are several which
      appear to not require NO to be present, HNO and NO(2). These two species have
      unique physiological effects and represent additional complexity to this
      biological picture. From this discussion, a picture can be formed concerning the
      possible chemical dynamics, which can be plausible in different biological
      mechanisms.

PMID- 15579021
TI  - HIF-1alpha and p53 as targets of NO in affecting cell proliferation, death and
      adaptation.
AB  - During the past years nitric oxide (NO) signaling became an integral component in
      understanding physiological and pathophysiological processes of cell
      proliferation, death or cellular adaptation. Among other activities NO affects
      multiple targets that allow regulation of gene expression. Although there is no
      evidence for direct NO-responsive DNA elements within promotor regions of
      eukaryotic genes numerous indirect signaling pathways exist to explain NO
      regulated gene expression. A characteristic feature of some transcription factors
      such as hypoxia inducible factor-1alpha (HIF-1alpha) or p53 (tumor suppressor
      p53) is their low protein abundance in unstressed cells due to efficient 26S
      proteasomal degradation of the protein. Characteristically, the protein amount of
      HIF-1alpha or p53 is increased steeply upon hypoxic stress or mechanisms that
      require activation of "guardian of the genome", i.e. p53. Current available data
      illustrate that NO is endowed with the ability to mimic a hypoxic response by
      stabilizing HIF-1alpha and/or to accumulate p53 and thus to affect viability
      decisions. Here we review recent advances in understanding molecular mechanisms
      how NO affects stability regulation of HIF-1alpha and p53. Moreover, we summarize
      existing concepts how HIF-1alpha and p53 interact to direct proliferation, death
      or adaptation. Considering HIF-1alpha and p53 as targets of reactive nitrogen
      intermediates (RNI) may provide insights into basic chemical reactions,
      biochemical signal transduction pathways with broad implications for medicine.

PMID- 15579022
TI  - Inflammatory modulation of hepatocyte apoptosis by nitric oxide: in vivo, in
      vitro, and in silico studies.
AB  - Nitric oxide (NO*) and its reaction products are key players in the physiology
      and pathophysiology of inflammatory settings such as sepsis and shock. The
      consequences of the expression of inducible NO* synthase (iNOS, NOS-2) can be
      either protective or damaging to the liver. We have delineated two distinct
      hepatoprotective actions of NO*: the stimulation of cyclic guanosine
      monophosphate and the inhibition of caspases by S-nitrosation. In contrast,
      iNOS/NO* promotes hepatocyte death under conditions of severe redox stress, such
      as hemorrhagic shock or ischemia/reperfusion. Redox stress activates an unknown
      molecular switch that transforms NO*, which is hepatoprotective under resting
      conditions, into an agent that induces hepatocyte death. We hypothesize that the
      magnitude of the redox stress is a major determinant for the effects of NO* on
      cell survival by controlling the chemical fate of NO*. To address this
      hypothesis, we have carried out studies in relevant in vivo and in vitro
      settings. Moreover, we have constructed an initial mathematical model of caspase
      activation and coupled it to a model describing some of the reactions of NO* in
      hepatocytes. Our studies suggest that modulation of iron, oxygen, and superoxide
      may dictate whether NO* is hepatoprotective or hepatotoxic.

PMID- 15579023
TI  - The role of iNOS in chronic inflammatory processes in vivo: is it damage
      promoting, protective, or active at all?
AB  - The expression of the inducible nitric oxide synthase (iNOS) is one of the direct
      consequences of an inflammatory process. Early studies have focused on the
      potential toxicity of the ensuing high-output NO-synthesis serving as a means to
      eliminate pathogens or tumor cells but also contributing to local tissue
      destruction during chronic inflammation. More recently, however, data are
      accumulating on a protective effect of high-output NO synthesis and - equally
      important - on a gene-regulatory function that helps to mount a protective stress
      response and simultaneously aids in down-regulating the proinflammatory response.
      These findings appear to contrast to the often observed sustained iNOS-expression
      during chronic inflammatory diseases, as for instance in Psoriasis vulgaris and
      other conditions with a chronic Th1-like reactivity. We here pose the question as
      to whether the iNOS is really active in these diseases. We review the data
      accumulated on iNOS expression in chronic diseases. We also report on the various
      factors that potentially interfere with proper NO formation by the expressed
      enzyme. We also highlight the recent findings of how, why and where evidences
      emerge that impeded NO formation contributes to chronic disease processes and
      finally present details on our current understanding of such abnormally low NO
      synthesis and its contribution to the pathophysiological processes of the human
      proinflammatory skin disease Psoriasis vulgaris.

PMID- 15579024
TI  - The dichotomous role of nitric oxide in the pathogenesis of accelerated
      atherosclerosis associated with systemic lupus erythematosus.
AB  - Atherosclerosis is an inflammatory disorder, and the inflammation associated with
      systemic lupus erythematosus (SLE) accelerates the development of
      atherosclerosis. Nitric oxide (NO) is an important mediator of inflammation
      including the inflammation associated with atherosclerosis and SLE. Endothelial
      nitric oxide synthase (NOS3)-mediated constitutive expression of NO promotes
      endothelial integrity and normal vascular function. In contrast, inducible nitric
      oxide synthase- (NOS2) mediated expression of NO promotes endothelial dysfunction
      and atherogenesis. Statins appear to have anti-inflammatory properties and
      reverse many of the deleterious effects associated with NO metabolism in
      atherosclerosis. Statins augment NOS3 expression and inhibit the induction of
      NOS2. Therefore, the balance between normal vascular function and atherogenesis
      may be mediated by differences in the quantity, location, and timing of NO
      production within vessel walls.

PMID- 15579026
TI  - Lessons from the Eker rat model: from cage to bedside.
AB  - Rodent models of human diseases serve a vital role in translating bench
      observations to bedside therapies. In vivo manipulation of these animals allows
      us to explore the biologic significance of the underlying molecular and
      biochemical pathways. The study of human cancers has been highly enriched by the
      observations made from numerous transgenic mouse models. Long before the
      techniques of genetic engineering were discovered, Dr. Reidar Eker described one
      of the earliest examples of an autosomal dominant model of renal tumors in a
      unique strain of rats. They were used in the 1980's by Alfred Knudson to validate
      the "two-hit" hypothesis and to study the multi-step process of carcinogenesis.
      Following the identification of the Tsc2 germline mutation in the Eker rat, it
      became the first rodent model of tuberous sclerosis and has since been exploited
      in many areas of tumor biology as illustrated in the content of this issue. The
      focus of our review is to highlight the contribution of the Eker rat towards
      understanding the Tsc2 signaling pathways in tumorigenesis and evaluating
      potential therapeutics in the pre-clinical setting.

PMID- 15579025
TI  - Cross-talk between nitric oxide and transforming growth factor-beta1 in malaria.
AB  - Malaria has re-emerged as a global health problem, leading to an increased focus
      on the cellular and molecular biology of the mosquito Anopheles and the parasite
      Plasmodium with the goal of identifying novel points of intervention in the
      parasite life cycle. Anti-parasite defenses mounted by both mammalian hosts and
      Anopheles can suppress the growth of Plasmodium. Nonetheless, the parasite is
      able to escape complete elimination in vivo, perhaps by thwarting or co-opting
      these mechanisms for its own survival, as do numerous other pathogens. Among the
      defense systems used by the mammalian host against Plasmodium is the synthesis of
      nitric oxide (NO), catalyzed by an inducible NO synthase (iNOS). Nitric oxide
      produced by the action of an inducible Anopheles stephensi NO synthase (AsNOS)
      may be central to the anti-parasitic arsenal of this mosquito. In mammals, iNOS
      can be modulated by members of the transforming growth factor-beta (TGF-beta)
      cytokine superfamily. Transforming growth factor-beta is produced as an inactive
      precursor that is activated following dissociation of certain inhibitory
      proteins, a process that can be promoted by reaction products of NO as well as by
      hemin. Ingestion by Anopheles of blood containing Plasmodium initiates parasite
      development, blood digestion which results in the accumulation of hematin (hemin)
      in the insect midgut, and induction of both AsNOS and TGF-beta-like (As60A) gene
      expression in the midgut epithelium. Active mammalian TGF-beta1 can be detected
      in the A. stephensi midgut up to 48h post-ingestion and latent TGF-beta1 can be
      activated by midgut components in vitro, a process that is potentiated by NO and
      that may involve hematin. Further, mammalian TGF-beta1 is perceived as a cytokine
      by A. stephensi cells in vitro and can alter Plasmodium development in vivo.
      Bloodfeeding by Anopheles, therefore, results in a juxtaposition of
      evolutionarily conserved mosquito and mammalian TGF-beta superfamily homologs
      that may influence transmission dynamics of Plasmodium in endemic regions.

PMID- 15579027
TI  - Multistep renal carcinogenesis in the Eker (Tsc 2 gene mutant) rat model.
AB  - Cancer is a heritable disorder of somatic cells. Environment and heredity both
      contribute to the origin of human cancer. The Eker (Tsc 2 gene mutant) rat model
      of hereditary renal carcinoma (RC) is an example of a Mendelian dominantly
      inherited predisposition to a specific cancer in an experimental animal. To the
      best of our knowledge, this was the first isolation of a Mendelian dominantly
      predisposing cancer gene in a naturally occurring animal model. Carcinogenesis
      looks like an opened Japanese fan, because initiated cells growing in several
      directions will develop into tumors having many gene abnormalities, and this is
      suggested by the edge of the fan. To search for such genetic alterations, we
      identified genes (Niban and Erc) that were expressed more abundantly in renal
      tumors than in the normal kidney.I will review this unique model for the study of
      multistep renal carcinogenesis and discuss cancer prevention and delay of
      carcinogenesis.

PMID- 15579028
TI  - The Eker rat: establishing a genetic paradigm linking renal cell carcinoma and
      uterine leiomyoma.
AB  - Renal Cell Carcinoma (RCC) and uterine leiomyoma (often referred to as fibroids)
      are tumors arising from tubular epithelium and myometrial compartments of the
      kidney and uterus, respectively. These tumors have a very different clinical
      presentation, with RCC being one of the less common cancers, having a very poor
      prognosis, and occurring predominantly in men, whereas uterine leiomyoma are the
      most common tumor of women and are benign. Although they are distinct
      histologically, with RCC arising from epithelial cells and leiomyoma arising from
      smooth muscle cells, they share a common embryological origin. Renal tubular
      epithelial cells arise during nephrogenesis as a result of the mesenchymal
      epithelial transition of condensed mesenchyme induced by the developing ureteric
      bud, and have a shared mesenchymal lineage with smooth muscle cells of the
      uterus. In addition to a common embryological origin, RCC and leiomyoma have been
      demonstrated to share a common genetic etiology. The Eker rat model was the first
      demonstration of a specific genetic linkage between RCC and uterine leiomyoma.
      Eker rats carry a germline defect in the rat homologue of the tuberous sclerosis
      complex 2 (TSC-2) tumor suppressor gene and develop spontaneous RCC and uterine
      leiomyoma with a high frequency. TSC patients are also at risk for RCC, and
      sporadic human uterine leiomyomas exhibit loss of function of the TSC-2 gene
      product, tuberin. Individuals with the inherited cancer syndrome hereditary
      leiomyomatosis and renal cell cancer (HLRCC) that have germline defects in the
      fumarate hydratase (FH) gene develop papillary RCC and uterine and skin
      leiomyomas. Benign cutaneous lesions and uterine leiomyoma also arise in German
      Shepherd dogs with germline mutations in the Birt-Hogg-Dube (BHD) gene, and these
      animals develop RCC and uterine leiomyoma with a high frequency. Identification
      of the tumor suppressor genes involved in these diseases, TSC, FH and BHD, and
      the elucidation of the function of their protein products, tuberin, fumarate
      hydratase and folliculin, respectively, opens new avenues for understanding the
      pathogenesis of both RCC and uterine leiomyoma.

PMID- 15579029
TI  - The genetic basis of kidney cancer: why is tuberous sclerosis complex often
      overlooked?
AB  - Fifty years ago, the Eker rat was identified as the first animal model of
      hereditary renal adenoma and carcinoma, with histopathology resembling human
      renal carcinoma. Ten years ago, a mutation in the TSC2 gene was identified in the
      Eker rat at Fox Chase Cancer Center by Yeung and Knudson, and in Tokyo by
      Kobayashi and Hino. The literature contains dozens of reports of renal cell
      carcinoma (RCC) in tuberous sclerosis complex (TSC) patients, including tumors in
      children as young as five and one report in an infant. Despite these facts, the
      association between TSC and RCC is under-recognized, and sometimes completely
      omitted from discussions of inherited renal carcinoma. Here, we will review the
      clinical association of RCC in TSC, consider the factors that have led to its
      under-emphasis within the RCC field, address the cellular and biochemical
      mechanisms that may contribute to RCC in cells with TSC1 or TSC2 mutations, and
      finally discuss the ways in which the TSC signaling pathways may be linked to
      sporadic RCC in the general population.

PMID- 15579030
TI  - Von Hippel-Lindau disease.
AB  - Germline mutations in the VHL tumour suppressor gene may cause a variety of
      phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma
      and inherited polycythaemia. VHL disease is a multisystem familial cancer
      syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL
      disease provides a paradigm for illustrating how studies of a rare familial
      cancer syndrome can produce advances in clinical medicin and important insights
      into basic biological processes. Thus the identification of the VHL gene has
      improved the diagnosis and clinical management of VHL disease and provided
      insights into the pathogenesis of sporadic clear cell RCC. Functional
      investigations of the VHL gene product have provided novel information on how
      cells sense oxygen and the role of hypoxia-response pathways in human
      tumourigenesis. Such information offers prospects of novel therapeutic
      interventions for VHL disease and common cancers including RCC.

PMID- 15579031
TI  - Familial non-syndromic clear cell renal cell carcinoma.
AB  - The diagnosis of familial non-syndromic clear cell renal cell carcinoma is one of
      exclusion. In families presenting with clear cell RCC a germline VHL mutation and
      a constitutional translocation of chromosome 3 must be excluded before familial
      non-syndromic clear cell RCC can be diagnosed. Large familial non-syndromic clear
      cell RCC kindreds are uncommon and a predisposing gene has not been identified.
      However inheritance is autosomal dominant in most cases and age at onset is
      earlier than in sporadic cases. Recognition and appropriate screening of familial
      non-syndromic clear cell RCC cases will reduce morbidity and mortality. Large
      scale collaborative linkage studies may provide a basis for the identification of
      familial non-syndromic clear cell RCC susceptibility gene(s).

PMID- 15579032
TI  - Chromosome 3 translocations and familial renal cell cancer.
AB  - Renal cell carcinomas (RCCs) occur in both sporadic and familial forms. In a
      subset of families the occurrence of RCCs co-segregates with the presence of
      constitutional chromosome 3 translocations. Previously, such co-segregation
      phenomena have been widely employed to identify candidate genes in various
      hereditary (cancer) syndromes. Here we survey the translocation 3-positive RCC
      families that have been reported to date and the subsequent identification of its
      respective candidate genes using positional cloning strategies. Based on allele
      segregation, loss of heterozygosity and mutation analyses of the tumors, a multi
      step model for familial RCC development has been generated. This model is
      relevant for (i) understanding familial tumorigenesis and (ii) rational patient
      management. In addition, a high throughput microarray-based strategy is presented
      that will enable the rapid identification of novel positional candidate genes via
      a single step procedure. The functional consequences of the (fusion) genes that
      have been identified so far, the multi-step model and its consequences for
      clinical diagnosis, the identification of persons at risk and genetic counseling
      in RCC families are discussed.

PMID- 15579033
TI  - Hereditary papillary renal carcinoma type I.
AB  - Germline missense mutations in the tyrosine kinase domain of the hepatocyte
      growth factor/scatter factor (HGF/SF) receptor, c-Met, are thought to be
      responsible for hereditary papillary renal carcinoma (HPRC) type 1, a form of
      human kidney cancer. In addition to extensive linkage analysis of HPRC families
      localizing the HPRC type 1 gene within chromosome 7, the demonstration that
      individual c-Met mutations reconstituted in cultured cells display enhanced and
      dysregulated kinase activity, and confer cell transformation and tumorigenicity
      in mice, solidifies this conclusion. Our prior knowledge of HGF/SF biology and c
      Met signaling enabled rapid progress in unraveling the molecular pathogenesis of
      HPRC type 1, and in laying the framework for the development of novel
      therapeutics for the treatment of this cancer. At the same time, the study of
      HPRC type 1 has refined our appreciation of the oncogenic potential of c-Met
      signaling, and challenges our current understanding of HGF/SF and c-Met function
      in health and disease.

PMID- 15579034
TI  - Hereditary leiomyomatosis and renal cell cancer (HLRCC).
AB  - Hereditary leiomyomatosis and renal cell cancer (HLRCC) (MIM 605839) is a
      recently identified autosomal dominant tumor susceptibility syndrome
      characterized by predisposition to benign leiomyomas of the skin and the uterus
      (fibroids, myomas). Susceptibility to early-onset renal cell carcinoma and
      uterine leiomyosarcoma is present in a subset of families. Renal cell carcinomas
      are typically solitary and aggressive tumors displaying papillary type 2 or
      collecting duct histology. The disease predisposing gene was identified as
      fumarate hydratase (fumarase, FH) (MIM 136850). FH encodes an enzyme that
      operates in the mitochondrial Krebs cycle being thus involved in cellular energy
      metabolism. The recent discovery of HLRCC and the predisposing gene FH has
      increased the present knowledge of hereditary renal cancer and enabled
      identification of the predisposed individuals. This review provides the present
      knowledge of the clinical, histopathological, and molecular features of HLRCC.
      Future prospects related to studies on the phenotype and molecular biology of
      HLRCC will also be discussed.

PMID- 15579035
TI  - Birt-Hogg-Dube syndrome, a genodermatosis that increases risk for renal
      carcinoma.
AB  - Over the past decade cancer-causing genes have been identified for the most
      common histologic types of renal cancer, specifically clear cell, papillary type
      1 and papillary type 2. Genes predisposing to the more rare chromophobe renal
      carcinoma and renal oncocytoma were unknown until the recent discovery of a novel
      gene, BHD, on chromosome 17p that was found to be mutated in the germline of
      affected family members with the Birt-Hogg-Dube (BHD) syndrome. These patients
      develop the hallmark BHD skin lesions (fibrofolliculomas), lung cysts and
      spontaneous pneumothorax. Importantly, BHD patients have an increased risk for
      developing a variety of renal neoplasia, most commonly chromophobe and oncocytic
      hybrid tumors. This review will describe the phenotypic manifestations of BHD
      including the histologic features of BHD-associated renal tumors, the
      identification of this novel renal cancer-predisposing gene, the BHD mutation
      spectrum found in BHD patients, and will discuss the potential role of BHD as a
      tumor suppressor gene.

PMID- 15579036
TI  - Natural history of the Nihon rat model of BHD.
AB  - Hereditary cancer was first described in the rat by Eker and Mossige in 1954 in
      Oslo. The Eker rat model of hereditary renal carcinoma (RC) was the first example
      of a Mendelian dominantly inherited predisposition to a specific cancer in an
      experimental animal, and has been contributing to the elucidation of renal
      carcinogenesis. Recently, we found a second hereditary RC model in the Sprague
      Dawley (SD) rat, in Japan in 2000, which was named the Nihon rat. The Nihon rat
      is also an example of a Mendelian dominantly inherited predisposition for
      development of RCs like the Eker rat, which are predominantly of the clear cell
      type (this type represents approximately 75 % of human RCC), and develop from
      earlier preneoplastic lesions than the Eker rat. We performed a genetic linkage
      analysis of the Nihon rat using 113 backcross animals, and found that the Nihon
      mutation was tightly linked to genes, which are located on the distal part of rat
      chromosome 10. Finally, we identified a germline mutation in the Birt-Hogg-Dube
      gene (Bhd) (rat chromosome 10, human chromosome 17p11.2) caused by the insertion
      of a single nucleotide in the Nihon rat gene sequence, resulting in a frame shift
      and producing a stop codon 26 amino acids downstream. Thus, the Nihon rat will
      contribute to understanding the BHD gene function and renal carcinogenesis.

PMID- 15579037
TI  - Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome.
AB  - Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a familial multi-tumor
      syndrome resulting from mutations in the HRPT2 tumor suppressor gene, which
      encodes a protein product named parafibromin. We review current knowledge of the
      renal manifestations of the HPT-JT syndrome, and examine recent advances in
      understanding the biological function of parafibromin.

PMID- 15579038
TI  - Magnetic resonance imaging of cell surface receptors using targeted contrast
      agents.
AB  - Over the past decade MR (magnetic resonance) imaging has emerged as one of the
      major modalities for noninvasive functional imaging. Recent advances in the
      development of targeted MR contrast agents have added significantly to the
      capabilities of MR imaging. In particular, the use of targeted contrast agents to
      report on the expression of cell surface receptors, combined with the functional
      capabilities of MR imaging, together provide unique opportunities to understand
      receptor-mediated pathways. In this article we have reviewed current MRI
      strategies used to visualize receptor expression, the potential advantages and
      drawbacks of these strategies, and novel areas of focus for the future.

PMID- 15579039
TI  - Novel paramagnetic contrast agents for molecular imaging and targeted drug
      delivery.
AB  - Molecular biology and genomic sciences are revealing the early biological
      signatures for many diseases. In response, the Molecular Imaging community is
      rapidly developing contrast agents to visualize the nascent pathological changes
      and to concomitantly deliver treatment directly to the site of disease. The
      evaluation, development and use of these new agents require a complementary
      understanding of contrast chemistry and imaging techniques. The fundamental
      issues surrounding magnetic contrast agent development, rational drug delivery,
      MR molecular imaging, and their interdependence are elucidated.

PMID- 15579040
TI  - Targeting cells with MR imaging probes based on paramagnetic Gd(III) chelates.
AB  - The low sensitivity is the major disadvantage of MRI as compared to PET.
      Therefore, amplification strategies are necessary for specific pathway labeling.
      This survey is aimed at exploring different routes to the entrapment of Gd(III)
      chelates in various type of cells at amounts sufficiently large to allow MRI
      visualization. Namely, the obtained results have been summarized in terms of
      internalization via i) pinocytosis; ii) phagocytosis; iii) receptors; iv)
      receptor mediated endocytosis; v) transporters; vi) transmembrane carrier
      peptides. MRI visualization of cells appears possible when the number of
      internalized Gd(III) chelates is of the order of 10(7)-10(8)/cell. Pinocytosis
      shows to be particularly useful for labeling cells that can be incubated for
      several hours in the presence of high concentrations of Gd-agent. This approach
      appears very effective for labeling stem cells. Nanoparticles filled with Gd
      chelates can be used for an efficient loading of cells endowed with a good
      phagocytic activity. Entrapment via receptors most often results in receptor
      mediated endocytosis. Suitably functionalized monomeric and multimeric Gd
      chelates can be considered for being internalized by this route as well as
      supramolecular systems such as those formed between Avidin and biotinylated Gd
      complexes. Exploitation of up-regulated transporters of nutrients in tumor cells
      appears to be a promising route for their differentiation from healthy cells.
      Finally, properly designed systems entering the cells by means of penetrin-like
      peptides deserve great attention.

PMID- 15579041
TI  - Activated MR contrast agents.
AB  - The relative non-specificity of the first generation MR contrast agents has meant
      that a new approach to their design is required. This review focuses on a new
      class of more specific or functional agents. These are the so-called "activated",
      "smart" or "responsive" contrast agents. The relaxivity of an activated contrast
      agent is responsive to (or can be modulated by) a particular in vivo stimulus
      such as a change in biological environment or activity. More specifically, a
      "switching on" of contrast in response to an event such as a change in
      physiological pH, metal ion concentration, enzyme activity or partial pressure of
      oxygen is sought. The current generation of activated MR contrast agents is
      discussed herein.

PMID- 15579042
TI  - Manganese enhanced magnetic resonance imaging.
AB  - Manganese is an essential metal that participates as a co-factor in a number of
      critical biological functions such as electron transport, detoxification of free
      radicals, and synthesis of neurotransmitters. Like other heavy metals, high
      concentrations of manganese are toxic. For example, chronic overexposure to
      manganese leads to movement disorders. In order to maintain this balance between
      being an essential participant in enzyme function and being a toxic heavy metal,
      a rich biology has evolved to transport and store manganese. Paramagnetic forms
      of manganese ions are potent MRI relaxation agents. Indeed, Mn(2+) was the first
      contrast agent proposed for use in MRI. Recently, there is renewed interest in
      combining the strong MRI relaxation effects of Mn(2+) with its unique biology in
      order to expand the range of information that can be measured by MRI. Manganese
      Enhanced MRI is being developed to give unique tissue contrast, assess tissue
      viability, act as a surrogate marker of calcium influx into cells and trace
      neuronal connections. In this article we review recent work and point out
      prospects for the future uses of manganese enhanced MRI.

PMID- 15579043
TI  - Dendrimer-based nanosized MRI contrast agents.
AB  - Paramagnetic metals can induce T1 shortening by interaction with free water
      molecules. Two metal ions, Gadolinium and Manganese, are currently available for
      human use. Gadolinium-based MRI contrast agents (CAs) can operate using a
      approximately 100-fold lower concentration of Gadolinium ions in comparison to
      the necessary concentration of Iodine atoms employed in CT imaging in the
      tissues. Therefore, numerous macromolecular MRI CAs prepared employing relatively
      simple chemistry are readily available that can provide sufficient enhancement
      for multiple applications. Herein, we describe the synthesis, characteristics,
      and potential applications of dendrimer-based macromolecular MRI CAs in our
      recently reported libraries. This entire series of dendrimer-based macromolecular
      MRI CAs have a spherical shape and possess similar surface charges. Changes in
      molecular size altered the route of excretion. Smaller sized contrast agents, of
      less than 60 kD molecular weight, were excreted through the kidney resulting in
      these agents being potentially suitable as functional renal contrast agents. Less
      hydrophilic and larger sized contrast agents were found better suited for use as
      blood pool contrast agents. Hydrophobic variants of CAs formed with
      polypropylenimine diaminobutane dendrimer cores quickly accumulated in the liver
      and can function as liver contrast agents. Larger hydrophilic agents are also
      useful for lymphatic imaging. Finally, contrast agents conjugated with either
      monoclonal antibodies or with avidin are able to function as tumor-specific
      contrast agents and might also be employed as therapeutic drugs for either
      gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

PMID- 15579044
TI  - A non-invasive approach to detecting organ rejection by MRI: monitoring the
      accumulation of immune cells at the transplanted organ.
AB  - Organ transplantation is the generally preferred medical procedure of treatment
      for patients with end-stage organ failure. The immunological reaction of
      rejection is a major cause of functional failure in transplant patients. The
      current "gold standard" for detecting or confirming graft rejection following
      solid organ transplantation requires biopsy samples in order to detect immune
      cell (e.g., T-cells, macrophages, etc.) infiltration into the graft and other
      pathological changes. This procedure is not only invasive, having associated
      risks, but is also prone to sampling errors that can yield false negative
      results. To circumvent the need for biopsies, we are developing magnetic
      resonance imaging (MRI) techniques to monitor the accumulation of immune cells at
      the transplanted organ as a means to detect graft rejection. By labeling immune
      cells with an MRI contrast agent, dextran-coated ultrasmall superparamagnetic
      iron oxide (USPIO) particles, we can monitor the accumulation of these labeled
      immune cells at the rejecting graft as a non-invasive method to detect graft
      rejection. Cells can be labeled ex vivo and then infused into the animal, or MRI
      contrast agents can be introduced directly into the animal in vivo. Our results
      show excellent correlation among the MRI signal intensity due to the USPIO
      labeled macrophages at the rejecting graft, immuno-staining for macrophages,
      histo-pathology for graft rejection, and the iron staining of tissue samples. In
      this article, we shall give a summary of our progress from detecting single
      immune cells in vitro to monitoring the accumulation of immune cells in vivo at
      the transplanted kidneys, hearts, and lungs in our rat models for organ
      transplantation by MRI.

PMID- 15579045
TI  - Monitoring cell therapy using iron oxide MR contrast agents.
AB  - Given the remarkable progress that has recently been obtained in animal studies,
      the clinical use of stem and progenitor cells to correct or replace defective
      cell populations may soon become a reality. In order to develop effective cell
      therapies, the location and distribution of these cells must be determined in a
      non-invasive manner. Magnetic resonance (MR) tracking of magnetically labeled
      cells following transplantation or transfusion may fulfill this requirement.
      Indeed, a series of recent studies indicate that MRI cell tracking has great
      potential for further evaluation and optimization of cell therapy. Due to its
      biocompatibility and strong effects on T2(*) relaxation, iron oxide nanoparticles
      appear to be the contrast agent of choice, and several methods now exist to
      shuttle sufficient amount of these compounds into cells. Most of the tracking
      work has been carried out in disease models of the central nervous system, but,
      recently, the infarcted heart has also received attention. With its excellent
      spatial resolution and the ability to track labeled cells over prolonged periods
      of time, MR monitoring of cell therapy is likely to become an important technique
      in the foreseeable future.

PMID- 15579046
TI  - Progress in the development of melanocortin receptor selective ligands.
AB  - The melanocortin pathway consists of endogenous agonists, antagonists, G-protein
      coupled receptors (GPCRs), and auxiliary proteins. This pathway has been
      identified to participate physiologically in numerous biological pathways
      including energy homeostasis, pigmentation, sexual function, inflammation,
      cardiovascular function, adrenal function, sebaceous gland lipid production, just
      to list a few. During this past decade, a clear link between the melanocortin-4
      receptor (MC4R) and obesity, in both mice and humans via the regulation of food
      intake and energy homeostasis, has made this pathway the target of many academic
      and industrial research endeavors in attempts to develop potent and selective
      MC4R small molecules as anti-obesity therapeutic agents. Herein, we attempt to
      summarize the known proteins that constitute the melanocortin system and discuss
      advances in peptide and non-peptide drug discovery.

PMID- 15579047
TI  - Inhibition of protein tyrosine phosphatase 1B as a potential treatment of
      diabetes and obesity.
AB  - Diabetes is a prevalent disease which effects over 150 million people worldwide
      and there is a great medical need for new therapeutic agents to treat it.
      Inhibition of protein tyrosine phosphatase 1B (PTP1B) has emerged as a highly
      validated, attractive target for treatment of not only diabetes but also obesity.
      Discovery of small-molecule inhibitors has been pursued extensively in both
      academia and industry and a number of very potent and selective inhibitors have
      been identified. With X-ray crystallography, the binding interactions of several
      classes of inhibitors have been elucidated. This has resulted in significant
      progress in understanding important interactions between inhibitors and specific
      residues of PTP1B, which could help the design of future inhibitors. However,
      since the active site of PTP1B that most of these inhibitors bind to is highly
      hydrophilic, it remains a challenge to identify inhibitors with both excellent in
      vitro potency and drug-like physiochemical properties which would lead to good in
      vivo activities.

PMID- 15579048
TI  - New pharmacological perspectives and therapeutic potential of PPAR-gamma
      agonists.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the
      nuclear hormone receptor superfamily has classically been characterized for its
      implications in adipocyte differentiation and fat metabolism. Recently, PPARgamma
      has been implicated in the pathophysiology of inflammatory and immune responses
      possibly through inhibition of the mitogen-activated protein kinase (MAPK)
      pathways or the activation of the transcription nuclear factor kappa B (NF
      kappaB). Thus, these agents might also have therapeutic potential in the
      treatment of gastrointestinal inflammatory disorders, such as ulcerative colitis
      and Crohn's disease. The synthetic thiazolidinediones (TZDs), a novel class of
      insulin-sensitizing drugs, were the first class of compounds identified as
      PPARgamma ligands, and represent a significant advance in anti-diabetic therapy.
      However, there is less information about endogenous ligands, although the
      prostaglandin (PG)J(2) and the oxidized phosphatidylcholine have been suggested.
      Furthermore, PPARgamma ligands have been shown to be potent inhibitors of
      angiogenesis, a process necessary for tumor growth and metastasis, and protect
      against cellular transformation. Further work is needed to establish in detail
      the anti-proliferative and pro-differentiation mechanisms of PPARgamma activators
      and their efficacy in certain cancers.

PMID- 15579049
TI  - Thyroid hormone ligands and metabolic diseases.
AB  - Thyroid hormones regulate fundamental genes involved in the metabolism,
      development and homeostasis of vertebrates. The endogenous hormones, L-3, 5, 3'
      triiodo-L-thyronine (T(3)) and L-3, 5, 3', 5'-tetraiodo-L-thyronine (T(4)), are
      of limited use in pharmacological intervention, mainly due to cardiovascular
      liabilities. There exist two subtypes of thyroid hormone receptors (TR), alpha
      and beta, unequally distributed in the body. As TRalpha is most abundant in the
      heart and most effects of thyroid hormones on the heart are mediated through
      TRalpha, a reasonable strategy is the development of TR agonists that either are
      tissue selective or that interact selectively with TRbeta. The prospects for the
      treatment of metabolic diseases with such ligands are considerable and this
      review describes the massive efforts of the academic and industrial communities
      during the last decade. It is, however, the author's view that the development of
      selective ligands only is in its infancy, an opinion highlighted by the limited
      chemical structural variation of TR ligands as well as the present lack of TR
      ligands for the treatment of metabolic diseases in clinical phases.

PMID- 15579050
TI  - Recent progress in work on PGD2 antagonists for drugs targeting allergic
      diseases.
AB  - Prostaglandin (PG) D(2), the major cyclooxygenase metabolite generated from
      immunologically stimulated mast cells, is thought to contribute to the
      pathogenesis of allergic diseases due to its various inflammatory effects.
      However, the lack of PGD(2) (DP) receptor antagonists has limited the study of
      its essential roles in the disease state. Recent discoveries of several DP
      receptor antagonists, the development of the mutant mouse and the discovery of a
      second PGD(2) receptor, CRTH2 (chemoattractant receptor-homologous molecule
      expressed on Th2 cells) receptor, have revealed the crucial roles of PGD(2) and
      CRTH2 receptors in allergic disorders. This review presents biological evidence
      that PGD(2) plays an essential role in allergy disorders and discusses the
      therapeutic possibilities of recently reported PGD(2) antagonists.

PMID- 15579051
TI  - Receptor tyrosine kinases are signaling intermediates of G protein-coupled
      receptors.
AB  - G protein-coupled receptors (GPCRs) can utilize receptor tyrosine kinases (RTKs)
      to mediate important cellular responses such as proliferation, differentiation
      and survival. Recent advances in the field suggest that GPCR-induced
      transactivation of RTKs might be important for diseases such as cancer and
      cardiac hypertrophy. Depending on the receptor and cell type, GPCR signaling
      involves activation of several different RTKs. By activating different subsets of
      RTKs, GPCRs can fine-tune their effects on target cells. Furthermore, RTK
      independent signaling pathways also initiated by GPCRs may modify the biological
      read out of the transactivated RTKs. This review focuses on the mechanisms how
      GPCRs and intracellular messengers elicit transactivation of different RTKs and
      the resulting different biological responses.

PMID- 15579052
TI  - Combination therapy of inhaled corticosteroids and long-acting beta2-adrenergics
      in management of patients with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) affects over 5% of the adult
      population and is the only major cause of death in the United States where
      morbidity and mortality are increasing. Clinically, COPD is characterized by
      irreversible airflow obstruction and airway inflammation that eventually lead to
      dyspnea, cough and sputum production. Long-acting beta(2)-agonists (LABAs) are
      effective in reducing patient symptoms through their bronchodilatory action on
      airway smooth muscle. More importantly, when LABAs are given in conjunction with
      inhaled corticosteroids, they appear to provide added benefits for patients.
      While the mechanisms for this observation are not entirely clear, there is
      emerging evidence to indicate that LABAs and corticosteroids attenuate different
      but complementary components of the inflammatory cascade related to COPD.
      Moreover, LABAs and corticosteroids may beneficially interact to prevent
      downregulation of beta(2)-receptors in airway cells (and thereby preventing
      tachyphylaxis) and to facilitate translocation of glucocorticoid receptors into
      the nucleus of inflammatory cells (thereby, amplifying the anti-inflammatory
      activity of the corticosteroid). Regardless of the mechanism, several large, high
      quality randomized controlled clinical trials indicate that combination therapy
      of LABA with inhaled corticosteroids improves patient symptoms, and reduces
      exacerbations by a third (compared to placebo). More importantly, combination
      therapy produces superior health outcomes than mono-therapy with inhaled
      corticosteroids or LABA, suggesting added clinical benefits of these two
      compounds in COPD. This article will present a comprehensive overview of the
      currently available clinical evidence for the use of combination therapy as well
      as the potential mechanisms of their actions in COPD.

PMID- 15579053
TI  - Quaternary ammonium derivatives as spasmolytics for irritable bowel syndrome.
AB  - Quaternary ammonium derivatives such as cimetropium, n-butyl scopolammonium,
      otilonium and pinaverium bromide have been discovered and developed as potent
      spasmolytics of the gastrointestinal tract. Their pharmacological activity has
      been proven in both "in vivo" and "in vitro" studies of hypermotility. "In vitro"
      experiments showed that they possess antimuscarinic activity at nM level but only
      pinaverium and otilonium are endowed with calcium channel blocker properties.
      These latter compounds relaxed the gastrointestinal smooth muscle mainly through
      a specific inhibition of calcium ion influx through L-type voltage operated
      calcium channels. Molecular pharmacology trials have indicated that pinaverium
      and otilonium can bind specific subunits of the calcium channel in the external
      surface of the plasma membrane and in this way they block the machinery of the
      contraction. Recent evidence showed that otilonium is able to bind tachykinin
      NK(2) receptors and not only inhibits one of the major contractile agents but can
      reduce the activation of afferent nerves devoted to the passage of sensory
      signals from the periphery to the central nervous system. Thanks to their typical
      physico-chemical characteristics, they are poorly absorbed by the systemic
      circulation and generally remain in the gastrointestinal tract where they exert
      the muscle relaxant activity by a local activity. Some differences exists in the
      absorption among these compounds: both n-butyl scopolammonium and cimetropium are
      partially taken up in the bloodstream, pinaverium has a low absorption (8-10 %)
      but is endowed with an excellent hepato-biliary excretion and otilonium, which
      has the lowest absorption (3 %), is almost totally excreted by faeces. Quaternary
      ammonium derivatives are widely used for the treatment of irritable bowel
      syndrome and recent meta-analyses have supported their efficacy in this disease.
      Due to its therapeutic index, the use of n-butyl scopolammonium is more indicated
      to treat acute colics than a chronic disease such as irritable bowel syndrome.
      Taking into consideration the published trials carried out with validated
      methodology in irritable bowel syndrome, cimetropium and otilonium are the best
      demonstrated drugs for the improvement in global assessment, pain and abdominal
      distension.

PMID- 15579054
TI  - Drug development and the importance of ethnicity: lessons from heart failure
      management and implications for hypertension.
AB  - Heart failure is a common condition, associated with both poor prognosis and poor
      quality of life. In contrast to all other cardiovascular diseases, the prevalence
      of heart failure is increasing in the western world, and is likely to continue to
      do so as the population ages. In the UK, a significant proportion of patients
      with heart failure come from South Asian and African Caribbean ethnic groups. A
      large body of evidence exists that there may be epidemiological and
      pathophysiological differences between patients with heart failure from different
      ethnic groups. Treatments such as ACE inhibitors, which are now part of standard
      heart failure therapy, have an evidence base consisting of trials in patients of
      almost exclusively white ethnicity. Such treatments may not be equally effective
      in patients from other ethnic groups. This review will discuss the current
      evidence for heart failure management with respect to ethnicity, and consider the
      implications for future drug development and implications for antihypertensive
      therapy.

PMID- 15579055
TI  - Sympathetic and baroreflex function in hypertension: implications for current and
      new drugs.
AB  - The sympathetic nervous system has moved towards center stage in cardiovascular
      medicine. The importance of the sympathetic activation in heart failure and in
      renal insufficiency progression and mortality is indeed now well established. In
      essential hypertension evidence has been provided that this may be the case,
      because sympathetic overactivity is a key factor in the pathophysiology of the
      disease, thereby promoting not only the blood pressure increase but also the
      development and progression of the hypertension-related cardiovascular and
      metabolic complications, such as left ventricular hypertrophy, vascular
      hypertrophy, endothelial dysfunction, cardiac rhythm disturbances and insulin
      resistance. In this review article the main pathophysiologic and mechanistic
      features of the sympathetic overactivity characterizing the essential
      hypertensive state will be examined. This will be followed by an analysis of the
      effects of 1) the hyperadrenergic state on the cardiovascular risk profile as
      well as on the end organ damage and 2) the different antihypertensive compounds
      on sympathetic and baroreflex function. The rationale for obtaining during
      antihypertensive drug treatment an effective sympathoinhibition will be finally
      highlighted.

PMID- 15579056
TI  - Endothelial dysfunction: methods of assessment and application to hypertension.
AB  - Interest in the endothelium has been growing in recent decades and the
      traditional belief that it provides an inert interface between blood and the
      vessel wall is no longer the case. It is now clear that the endothelium produces
      a large number of substances that influence blood flow, and it is in turn
      affected by changes in the blood and the pressure of blood flow. Nitric oxide and
      endothelins are the major regulators of the vascular tone, and thereby the blood
      pressure. Historically speaking, concepts such as endothelial cell damage and
      injury were described in the 1960s and 1970s. More recently, terms such as
      endothelial cell activation and dysfunction have also been introduced. Although
      similar in some respects or part of a continuum, these terms differ in the actual
      effects on the endothelium, and hence differentiation is important. In
      hypertension, the delicate balance between the vasodilators and the
      vasoconstrictors is upset, with disturbance in the nitric oxide pathways that
      lead to a predominance of the vasoconstrictors. This in turn leads to many other
      changes that take place in the endothelium, setting up a vicious cycle that
      maintains the high blood pressure. Therefore, accurate assessment of vascular
      function is important in linking pathophysiology with clinical disease, such as
      hypertension. Indeed, there are several methods currently employed experimentally
      to assess endothelial dysfunction. However, the most widely studied and accepted
      tests are the estimation of plasma markers such as von Willebrand factor, E
      selectin and thrombomodulin, and studies of forearm circulation in response to
      hypoxia induced stress ('flow mediated dilatation', FMD) or intra arterially
      administered drugs such as acetyl choline. The present document examines these
      topics. Whilst acknowledging the debt owed to animal models in the study of
      hypertension, we shall focus on work where primary study is in homo sapiens. A
      greater appreciation of how endothelial assessments are made in hypertension will
      have relevance for drug development and future management strategies.

PMID- 15579057
TI  - Antihypertensive therapy and endothelial function.
AB  - The benefits of treating hypertension in terms of reduction of morbidity and
      mortality are well established. However, it is debatable whether this benefit is
      derived entirely from the effects of a reduced blood pressure or whether these
      agents exert effects over and above blood pressure reduction on the endothelium.
      Hypertension is associated with adverse changes (whether damage or dysfunction)
      in the endothelium. Indeed, endothelial damage/dysfunction has have been
      demonstrated to be a reliable prognostic indicator of future cardiovascular
      events in hypertension. Of the various drug classes, calcium channel blockers and
      the ACE inhibitors have significant direct effects on the endothelium. This is in
      contrast to the beta blockers and alpha adrenergic blockers that appear to
      indirectly influence endothelial function solely as a result of lowered blood
      pressure. Antioxidants may have a beneficial effect on endothelial function as
      well, although their clinical use does not seem to translate into clinical
      benefit.

PMID- 15579058
TI  - Hypertension in peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) of the lower limbs is associated with a high
      cardiovascular morbidity and mortality. Intermittent claudication is the most
      common symptomatic manifestation of PAD, but is in its own value an important
      predictor of cardiovascular death, increasing it by three-fold, and increasing
      all-cause mortality by two-to-five fold. Hypertension is a risk factor for
      vascular disorders, including PAD. Of hypertensives at presentation, about 2-5%
      have intermittent claudication, with increasing prevalence with age. Otherwise,
      35-55% of patients with PAD at presentation also show hypertension. Patients who
      suffer from hypertension with PAD have a greatly increased risk of myocardial
      infarction and stroke. There is no consensus on the specific treatment of
      hypertension in PAD because of the limited controlled studies on antihypertensive
      therapy in such specific PAD population. There is an obvious need of such outcome
      studies, especially since the two conditions are frequently encountered together.
      However, as risk is high in all PAD patients, the most important goal remains to
      decrease the global cardiovascular risk in such patients rather than to focus on
      the control of blood pressure only and on the reduction of symptoms of PAD.
      Therefore, treatment with antiplatelet drugs, ACE-inhibitors and statins should
      be considered.

PMID- 15579059
TI  - Pathophysiology and treatment of obesity hypertension.
AB  - Excess weight gain accounts for as much as 65-75% of the risk for essential
      hypertension and also greatly increases the risk for end stage renal disease
      (ESRD). Obesity raises blood pressure by increasing renal tubular reabsorption,
      impairing pressure natriuresis, and causing volume expansion due to activation of
      the sympathetic nervous system (SNS) and renin-angiotensin aldosterone system
      (RAAS), and by physical compression of the kidneys, especially when visceral
      obesity is present. The mechanisms of SNS activation in obesity are still unclear
      but may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro
      opiomelanocortin (POMC) pathway. With prolonged obesity, there may be a gradual
      loss of kidney function that worsens with time, exacerbates hypertension, and
      makes blood pressure more difficult to control. Lifestyle modifications,
      including weight reduction and increased physical activity, are essential first
      steps in the management of obesity hypertension and renal disease. Anti-obesity
      drugs offer potential pharmacotherapy for obesity hypertension, but current drugs
      are very limited and additional long-term studies are needed to test their safety
      and efficacy. Clinical trials are also needed to determine the most effective
      antihypertensive drugs for obese hypertensive patients. Special considerations
      for the obese patient, in addition to adequately controlling the blood pressure,
      include correcting the metabolic abnormalities and protecting the kidneys from
      further injury.

PMID- 15579060
TI  - Propofol: therapeutic indications and side-effects.
AB  - Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is
      widely used for the induction and maintenance of anesthesia and for sedation in
      the intensive care unit. Propofol is an oil at room temperature and insoluble in
      aqueous solution. Present formulations consists of 1% or 2% (w/v) propofol, 10%
      soybean oil, 2.25% glycerol, and 1.2% egg phosphatide. Disodium edetate (EDTA) or
      metabisulfite is added to retard bacterial and fungal growth. Propofol is a
      global central nervous system depressant. It directly activates GABA(A)
      receptors. In addition, propofol inhibits the NMDA receptor and modulates calcium
      influx through slow calcium ion channels. Propofol has a rapid onset of action
      with a dose-related hypnotic effect. Recovery is rapid even after prolonged use.
      Propofol decreases cerebral oxygen consumption, reduces intracranial pressure and
      has potent anti-convulsant properties. It is a potent antioxidant, has anti
      inflammatory properties and is a bronchodilator. As a consequence of these
      properties propofol is being increasingly used in the management of traumatic
      head injury, status epilepticus, delirium tremens, status asthmaticus and in
      critically ill septic patients. Propofol has a remarkable safety profile. Dose
      dependent hypotension is the commonest complication; particularly in volume
      depleted patients. Hypertriglyceridemia and pancreatitis are uncommon
      complications. Allergic complications, which may include bronchospasm, have been
      reported with the formulation containing metabisulfite. In addition, this
      formulation has been demonstrated to result in the generation of oxygen free
      radicals. High dose propofol infusions have been associated with the "propofol
      syndrome"; this is a potentially fatal complication characterized by severe
      metabolic acidosis and circulatory collapse. This is a rare complication first
      reported in pediatric patients and believed to be due to decreased transmembrane
      electrical potential and alteration of electron transport across the inner
      mitochondrial membrane.

PMID- 15579061
TI  - Structurally modified analogues of glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP) as future antidiabetic agents.
AB  - Glucagon-like peptide-1(7-36)amide (GLP-1) and glucose-dependent insulinotropic
      polypeptide (GIP) are gastrointestinal insulin-releasing hormones involved in the
      regulation of postprandial nutrient homeostasis. These two incretin hormones are
      glucose-dependent stimulators of pancreatic beta-cell function, exhibiting a
      spectrum of secondary extrapancreatic activities, which favour the efficient
      control of blood glucose homeostasis. Such actions of GLP-1 and GIP have
      generated considerable interest in their possible exploitation as novel agents
      for the treatment of type 2 diabetes. Despite the many attributes of GLP-1 and
      GIP as possible future antidiabetic agents, their rapid degradation in the
      circulation by dipeptidyl peptidase IV (DPP IV) to inactive truncated forms GLP
      1(9-36)amide and GIP(3-42), severely limits their therapeutic usefulness. This
      review will consider recent developments in the design and effectiveness of
      synthetic DPP IV-resistant analogues of GLP-1 and GIP. Consideration will be
      given to the effects of N-terminal modification and amino acid substitution of
      GLP-1 and GIP either side of the DPP IV cleavage site on (i) susceptibility to
      enzymatic degradation, (ii) binding to native hormone receptor, (iii) ability to
      elevate intracellular cyclic AMP, (iv) potency as insulin secretagogues, and (v)
      antihyperglycaemic activity in type 2 diabetes. It will be shown that structural
      modification can produce a varied set of biological activities, ranging from more
      efficacious analogues to those which antagonise the activity of the native
      hormone. The antidiabetic properties of the best GLP-1 and GIP analogues indeed
      promise to provide the basis for novel, effective and long-acting drugs for type
      2 diabetes therapy. This approach is currently being pursued actively by the
      pharmaceutical industry.

PMID- 15579062
TI  - In utero gene therapy: prospect and future.
AB  - Many genetic disorders are reported to cause irreversible damage to the fetus
      before birth. In utero gene therapy may be an effective tool for correction of
      genetic disorders by replacing defective gene with normal one. There are many
      reasons for moving forward with in utero gene therapy. The most important reason
      is to provide early intervention as to prevent or slow dysfunction and morbidity.
      This approach may prove to be advantageous in rapidly replicating fetal cells,
      and less sensitive to immune response to vector or transgene product due to
      underdeveloped immune system. In addition, the developing fetus may be a better
      candidate for gene therapy than the adult because gene engraftment may be more
      feasible in early fetal life, where stem cells or pleuripotent progenitor cells
      are more accessible to vectors. Some reports are available on successful in utero
      gene transfer in animal models but many questions remain to be answered before in
      utero gene therapy can be considered a viable solution to human. The real moral
      challenge facing in utero gene therapy is finding ways to insure that the review
      of protocols is adequate, and that those undertaking trials are competent to do
      so. Present review article analyzes the overall progress of the field, and the
      research that still needs to be performed before it can be considered to human
      clinical trials.

PMID- 15579063
TI  - TNF-related apoptosis-inducing ligand (TRAIL): a potential candidate for combined
      treatment of hematological malignancies.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF gene
      superfamily, which induces apoptosis through engagement of death receptors. TRAIL
      is unusual as compared to the other cytokines of this family, as it interacts
      with a complex system of receptors consisting of two pro-apoptotic death
      receptors (TRAIL-R1 and TRAIL-R2) and three decoy receptors (TRAIL-R3, TRAIL-R4
      and osteoprotegerin). Moreover, with respect to other members of the TNF
      superfamily, such as CD95L and TNF-alpha, TRAIL has generated great interest as a
      potential tumor-specific cancer therapeutic because as a stable soluble trimer it
      selectively induces apoptosis in many transformed cells but not in normal cells.
      Of note, TRAIL cytotoxicity is at least partially independent of the major
      systems involved in resistance to chemotherapy, such as p53 wild-type function
      and multidrug resistance (MDR) genes. Since one fundamental problem of most
      cancers is the development of multiple mechanisms of resistance, which
      progressively reduce or suppress the therapeutic efficacy of conventional
      chemotherapy, new therapeutic approaches that either restore the pro-apoptotic
      activity of chemotherapeutic drugs or by-pass the mechanisms of resistance are
      highly desirable. This review will focus on the potential of TRAIL for its
      application in the therapy of hematological malignancies, used either alone or in
      combination with chemotherapy. The scenario emerging from the literature is that
      the treatment and management of hematological malignancies will require the
      rational combination of TRAIL plus conventional or new drugs in a regimen that
      would optimize the anti-neoplastic activity in malignant cells resistant to
      chemotherapy through restoration of the pro-apoptotic activity of TRAIL.

PMID- 15579064
TI  - Point of NO return for nitrergic nerves in diabetes: a new insight into diabetic
      complications.
AB  - Aberrations in nitrergic neurotransmission, due to a decrease in neuronal nitric
      oxide (NO) synthase (nNOS) protein, play an important role in the pathogenesis of
      autonomic neuropathy in diabetes. Until recently the mechanism of the decrease in
      nNOS protein content in nitrergic nerves during diabetes was debated. Two
      different views were prevailing, one attributing the nNOS decrease to nitrergic
      nerve degeneration, the other to an alteration in nNOS expression. Our recent
      study in which we showed that nitrergic nerves undergo a degenerative process in
      two phases might bring a solution to this debate. Our model suggests that, in the
      early stages of diabetes, nNOS expression is decreased in the nitrergic axons
      while nNOS levels are unaffected in the cell bodies, most probably due to a
      defect in axonal transport. This decrease is reversible with insulin treatment.
      As the diabetes progresses, nNOS starts to accumulate in the cell bodies since it
      cannot be transported down to the axons. Increased nNOS protein and NO production
      coincide with accumulation of advanced glycation endproducts (AGEs) in the blood
      and tissues. Synergistic action of AGEs and endogenous NO leads to increased
      oxidative stress within the cell bodies, resulting in apoptosis. This
      degenerative phase of nitrergic neuropathy is not reversible with insulin
      treatment. This suggests a point of no return for autonomic nerves after which
      the degenerative changes become irreversible. Future therapeutic approaches could
      target the defective axonal transport and prevention of AGEs accumulation before
      this point of no return. In the later stages, reduction of AGEs, replenishment of
      lost nitrergic neurons and restoration of function are putative therapeutic
      targets.

PMID- 15579065
TI  - Virus attachment and entry offer numerous targets for antiviral therapy.
AB  - In 2003 the first virus entry inhibitor, the anti-HIV peptide T20 (Fuzeon,
      enfuvirtide), was approved for treatment of advanced Human Immunodeficiency Virus
      Type 1 infection. T20 is an unconventional antiviral drug, as it does not target
      a viral replicase or protease but a conformational transition within the HIV1
      fusion protein gp41 required for virus-cell membrane fusion. Beyond membrane
      fusion, numerous early drug targets have been identified that will allow for
      large scale screening or structure-based drug design. The first encounter of the
      virus with the host might be through binding to attachment receptors, such as the
      C-type lectins DC- and L-SIGN, which might play an important role of infection
      for a large number of enveloped viruses by capturing, concentrating and
      transmitting infectious virions. Once a virus reaches its target cell, a cascade
      of events generally starting with the interaction of viral envelope glycoproteins
      with specific entry receptors and co-receptors is necessary in order to trigger
      the virus-cell membrane fusion. The present review will highlight recent advances
      in the identification of new drugs and targets at the level of virus entry for
      three major human pathogens accounting for several hundred million infections
      worldwide: HIV, Dengue Virus and Hepatitis C virus.

PMID- 15579066
TI  - Closely related antiretroviral agents as inhibitors of two HIV-1 enzymes,
      ribonuclease H and integrase: "killing two birds with one stone".
AB  - The structures of the catalytic core of two HIV-1 encoded enzymes play a crucial
      role in the retroviral cycle: integrase and RNase H exhibit striking
      similarities. These enzymes also share a similar mechanism of catalysis. The
      homologies between RNase H and integrase led to studying the effect of the RNase
      H inhibitors on integrase. ODNs aptamers active on RNase H were shown to be
      strong IN inhibitors. On the contrary, compounds from the diketo acid family were
      previously known as integrase inhibitors. One compound of this family is able to
      inhibit the RNase H activity, but has no effect on integrase. Cellular
      topoisomerase 1 also shares a mechanism similar to that of HIV-1 integrase and
      RNase H. It has been reported to be present in retroviral particles and to
      enhance cDNA synthesis. Some topoisomerase inhibitors have been shown to be
      active on integrase. Moreover, topoisomerase, integrase and RNase H are inhibited
      by G-rich oligonucleotides. A G-quartet structure is necessary for integrase, but
      not for topoisomerase inhibition. This suggests that prototype structures can be
      exploited to develop inhibitors of two related enzymes, such as the RNase H and
      integrase activities of HIV-1 RT.

PMID- 15579067
TI  - Targeting the assembly of the human immunodeficiency virus type I.
AB  - In the rush to develop anti-viral drugs against the human immunodeficiency virus
      type I (HIV-1), all the steps of the viral life cycle are potential targets of
      therapeutic intervention. In this review, we will explore the recent advances on
      strategies that aim at obstructing the formation, the release and the infectivity
      of newly formed virion particles from HIV-1 infected cells.

PMID- 15579068
TI  - Three properties of the hepatitis C virus RNA genome related to antiviral
      strategies based on RNA-therapeutics: variability, structural conformation and
      tRNA mimicry.
AB  - The concept of using RNA molecules as therapeutic agents is receiving increasing
      attention by basic science and pharmaceutical research. Over the past five years,
      a number of clinical trials have been initiated to evaluate the efficacy and
      safety of several RNA agents for the treatment of a range of conditions from
      cancer to infectious disease. From a molecular biology perspective, two main
      factors are implicated in RNA therapeutics against pathogenic RNAs: i/ The
      activity, stability and delivery of the inactivating agent (ribozyme, RNase P,
      "decoy" RNA, aptamer, small interfering-RNA) and its co-localisation with the
      target; and ii/ The properties of the RNA substrate, which, in the case of an RNA
      virus, most likely limit the effectiveness of the inactivating agent. The main
      reasons are the limited size of the viral genome and the restrictions imposed by
      the RNA structure and variations at the target. In the first section of this
      article we review three properties of the HCV RNA genome, from primary sequence
      to tertiary structure, which imply restrictions and opportunities for RNA-based
      treatment. In the second section, we briefly describe several of the RNA-based
      therapeutic strategies against HCV now under development.

PMID- 15579069
TI  - Picornavirus IRES: structure function relationship.
AB  - Picornavirus infections have been a challenging problem in human health. Genome
      organisation of picornavirus is unique in having a long, heavily-structured,
      multifunctional 5'untranslated region, preceding a single open reading frame from
      which all viral proteins are produced. Within the 5'leader, an internal region
      termed ribosome entry site (IRES) regulates viral protein synthesis in a 5'
      independent manner. The IRES element itself is a distinctive feature of the
      picornavirus mRNAs, allowing efficient viral protein synthesis in infected cells
      in spite of a severe modification of translation initiation factors induced by
      viral proteases that lead to a fast inhibition of cellular protein synthesis.
      Picornavirus IRES elements are strongly structured, bearing several motifs,
      phylogenetically conserved, which are essential for IRES activity. Together with
      RNA structure, RNA-binding proteins play an essential role in the activity of the
      IRES element, having a profound effect on viral pathogenesis. Recent data on the
      involvement of these conserved motifs in RNA structure and protein recognition is
      discussed in detail. Understanding the interplay between these two components of
      IRES function is crucial to develop viral strategies aimed to use the viral RNA
      as the target of antiviral approaches.

PMID- 15579070
TI  - Replication and transcription of the rotavirus genome.
AB  - Rotaviruses are an important cause of human morbidity and mortality, representing
      the primary pathogens responsible for acute dehydrating diarrhea in children
      under the age of 3. The infectious rotavirus particle is made up of three
      concentric layers of protein, and contains a genome consisting of eleven segments
      of double-stranded (ds)RNA. Upon infection, RNA polymerases associated with
      double-layered virus particles are activated, resulting in genome transcription
      and extrusion of the eleven viral mRNAs from such particles. The mRNAs not only
      direct protein synthesis, but also serve as templates for minus-strand synthesis
      to yield dsRNAs. Synthesis of the dsRNAs is an event that occurs following the
      gene-specific packaging of viral mRNAs into core-like assembly intermediates.
      Electron-dense cytoplasmic inclusions, termed viroplasms, function as sites of
      genome packaging and replication in the infected cell. Our understanding of key
      events in the viral life cycle has been advanced considerably by the development
      of cell-free systems that support mRNA synthesis from virion-derived double
      layered particles and dsRNA synthesis from virion-derived core particles. The
      recent expression and purification of rotavirus recombinant proteins have also
      allowed progress to be made in defining the roles of viral proteins in genome
      replication and viroplasm formation. However, our efforts towards a full
      description of the viral life cycle, most notably an understanding of the events
      occurring during gene-specific packaging, remain hampered by the lack of a cell
      free packaging system and a reverse genetics systems. The lack of a reverse
      genetics systems also confounds efforts towards the generation of molecular
      engineered second-generation vaccines.

PMID- 15579071
TI  - Coumarin and isocoumarin as serine protease inhibitors.
AB  - Serine proteases are attractive targets for the design of enzyme inhibitors since
      they are involved in the etiology of several diseases. Within the class of serine
      proteases, HLE is one of the most destructive enzymes in the body. It is
      implicated in the promotion or exacerbation of a number of diseases including
      pancreatitis, acute respiratory syndrome, rheumatoid arthritis, atherosclerosis,
      pulmonary emphysema, and cystic fibrosis. Thrombin, a trypsin-like serine
      protease, plays a dual role in thrombogenesis, including fibrin formation and
      platelet activation. As a result, thrombin constitutes one of the most widely
      studied targets for antithrombotic strategy. Numerous inhibitors of serine
      proteases have been reported during the past three decades. Among them, coumarin
      type molecules displayed a high inhibitory potency towards various serine
      proteases. At that time, halomethyl dihydrocoumarins have been shown to behave as
      the first general suicide inhibitors of serine protease. These molecules inhibit
      several proteases such as human leucocyte elastase, porcine pancreatic elastase,
      thrombin, urokinase and human plasmin. Isocoumarins are very effective as
      mechanism-based inhibitors of serine proteases. Pharmacomodulation on the 3
      alkoxy-4-chloroisocoumarins and the 3-alkoxy-7-amino-4-chloroisocoumarins led to
      strong inhibitors of numerous serine proteases such as HLE, human factor XIa and
      XIIa, thrombin, urokinase and kallikrein. Recently, a series of coumarins
      characterised by an alkyl, aryl ester, amide, thioester or ketone in the position
      3 and an electrophilic chloromethyl moiety in the position 6 have been developed.
      These compounds were found to be high inhibitors of alpha-chymotrypin, HLE and
      human thrombin.

PMID- 15579072
TI  - Studies on coumarins and coumarin-related compounds to determine their
      therapeutic role in the treatment of cancer.
AB  - The Benzopyrones are a group of compounds whose members include coumarins and
      flavonoids. Dietary exposure to benzopyrones is quite significant, as these
      compounds are found in vegetables, fruit, seeds, nuts, coffee, tea and wine. It
      is estimated that the average western diet contains approximately 1 g/day of
      mixed benzopyrones. It is, therefore, not difficult to see why extensive research
      into their pharmacological and therapeutic properties is underway over many
      years. Coumarin is a natural substance that has shown anti-tumour activity in
      vivo, with the effect believed to be due to its metabolites (e.g. 7
      hydroxycoumarin). This review is based on recent studies of coumarins and
      coumarin related compounds. Therefore, the focus will be on these relevant
      compounds and their therapeutic importance. A recent study has shown that 7
      hydroxycoumarin inhibits the release of Cyclin D1, which is overexpressed in many
      types of cancer. This knowledge may lead to its use in cancer therapy. Esculetin
      inhibits growth and cell cycle progression by inducing arrest of the G(1) phase
      in HL-60 leukaemia cells, resulting from the inhibition of retinoblastoma protein
      phosphorylation. Recent studies investigating the potential of flavonoids as
      therapeutic agents have suggested they may have use in various therapeutic
      settings ranging from leukaemia treatment to the treatment of patients with HIV.
      Genistein is a well-known isoflavone and is a tyrosine kinase inhibitor. Studies
      have indicated that genistein elicits inhibitory effects on cell growth of
      various carcinoma cell-lines and may be a potential candidate for cancer therapy.
      In our research, we have investigated the effects of coumarins and coumarin
      related compounds on a panel of cell-lines. The most recent work involves two
      cell-lines, MCF-7 a breast carcinoma and A549 a lung carcinoma. Microtitre assays
      were performed along with real-time analysis of cell viability using a biosensor
      called the Cytosensor microphysiometer. These studies suggest that both genistein
      and esculetin exerted the most potent inhibitory effect on cell growth in
      comparison to the other two compounds.

PMID- 15579073
TI  - Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant
      activities.
AB  - Several natural products with a coumarinic moiety have been reported to have
      multiple biological activities. It is to be expected that, in a similar way to
      isomeric flavonoids, coumarins might affect the formation and scavenging of
      reactive oxygen species (ROS) and influence processes involving free radical
      mediated injury. Coumarin can reduce tissue edema and inflammation. Moreover
      coumarin and its 7-hydroxy-derivative inhibit prostaglandin biosynthesis, which
      involves fatty acid hydroperoxy intermediates. Natural products like esculetin,
      fraxetin, daphnetin and other related coumarin derivatives are recognised as
      inhibitors not only of the lipoxygenase and cycloxygenase enzymic systems, but
      also of the neutrophil-dependent superoxide anion generation. Due to the
      unquestionable importance of coumarin derivatives considerable efforts have been
      made by several investigators, to prepare new compounds bearing single
      substituents, or more complicated systems, including heterocyclic rings mainly at
      3-, 4- and/or 7-positions. In this review we shall deal with naturally occurring
      or synthetically derived coumarin derivatives, which possess anti-inflammatory as
      well as antioxidant activities.

PMID- 15579074
TI  - The coumarin moiety as chromophore of fluorescent ion indicators in biological
      systems.
AB  - Fluorescent probes have evolved into an extremely useful tool for the detection
      of ions in biological systems. The design of ion indicators is based in the
      proper choice of the ion chelating group as well as the chromophore moiety. The
      chromophores of choice should fulfill a number of requirements concerning the
      photostability of the group, the range of the excitation and emission wavelengths
      of the indicators, the Stokes shift, the fluorescence quantum yield, the
      excitation and/or emission wavelength shift upon coordination of the probe with
      its target ion, the lipophilicity of the indicators, and their possible cell
      toxicity. Coumarin and its analogues have been extensively used in ion detection
      by incorporation of the coumarin chromophore in the larger indicator framework.
      Coumarins fulfill all the aforementioned requirements since they are relatively
      photostable and their excitation and emission maxima, in many cases, are long
      enough to minimise "background" fluorescence of cellular components, tissues and
      biological fluids. They exhibit Stokes shifts large enough to avoid significant
      overlap of the excitation and emission spectra, their fluorescence quantum yields
      allow for ion detection at low indicator concentrations, and they can be
      introduced to cells either by microinjection or as membrane permeable derivatives
      without causing cell death. Synthetic approaches, aiming at the optimisation of
      indicator properties, have extended the conjugated coumarin system either by
      introduction of substituents or by expansion of the heterocyclic system. In this
      review, the basic rationale for the selection of the particular coumarin
      analogues is analysed, synthetic pathways leading to the desired structures are
      presented, and properties and relative advantages in the use of these probes are
      described.

PMID- 15579075
TI  - Analysis of fish IL-1beta and derived peptide sequences indicates conserved
      structures with species-specific IL-1 receptor binding: implications for
      pharmacological design.
AB  - A large number of IL-1 protein sequences have become available recently from a
      range of vertebrate species and especially from bony fish. However, 3D structures
      are still only known for mammalian IL-1. In this review, we use a multiple
      sequence alignment of all published non-mammalian vertebrate IL-1beta proteins to
      locate the structurally important residues critical for maintaining the beta
      trefoil fold and we investigate the degree to which functionally important
      residues involved in receptor binding are conserved across vertebrate species. We
      find that although there is a high level of variability of positions involved in
      receptor binding, the mode of binding and overall shape of the ligand-receptor
      complex is probably maintained. This implies that each species has evolved its
      own unique interleukin-1 signalling system through ligand-receptor co-evolution.
      Nonetheless, the IL-1beta processing mechanism in non-mammalian vertebrates
      remains unclear because, with the exception of three bony fish, all non-mammalian
      IL-1beta sequences discovered so far lack an ICE (Interleukin Converting Enzyme)
      cut site. The IL-1 system has become an important drug target because of its
      significance in inflammatory diseases. Research on peptides derived from IL-1beta
      has identified peptides that possess agonist activity in humans and in trout, and
      peptides with antagonist activity. The agonist peptides map to two distinct loop
      regions of IL-1beta that are known to interact with the flexible domain III of
      the corresponding receptor. Further analysis of the IL-1 system may prove useful
      in engineering IL-1 with improved features and in suggesting new avenues for
      therapeutic intervention.

PMID- 15579076
TI  - Structural features of the interleukin-10 family of cytokines.
AB  - The interleukin-10 (IL-10) family of cytokines includes IL-10, a number of its
      viral gene homologs, and eight recently discovered cellular cytokines (IL-19, IL
      20, IL-22, IL-24, IL-26, IFN-lambda1, IFN-lambda2, IFN-lambda3). IL-10 is an
      intercalated dimer consisting of two six-helix bundle domains. Signal
      transduction occurs when each domain of IL-10 binds to two receptor chains, IL
      10R1 and IL-10R2. Viral homologs use the same IL-10 receptor system, while
      cellular homologs use their own receptors: three long receptor chains (IL-20R1,
      IL-22R1 and IFN-lambda1R1) and two short receptor chains (IL-20R2 and IL-10R2).
      Most of the cellular homologs belong to the IL-19 subfamily of cytokines
      including IL-19, IL-20, IL-22 and IL-24. It is likely that IFN-lambda1, IFN
      lambda2, and IFN-lambda3 also belong to the same subfamily. All these proteins
      are monomers in solution. Crystal structures of IL-19 and IL-22 show that the
      molecules consist of seven helices (A-G) forming a seven-helix bundle with
      compact hydrophobic core inside. Structures of complexes of IL-10 and CMVIL-10
      with an extracellular domain of high affinity receptor IL-10R1 (sIL-10R1) showed
      that ligand/receptor interactions are of mostly polar nature, with two
      hydrophobic patches around receptor residues Tyr43 and Phe143 at the top and
      bottom of the interface. The location and structure of the binding site for the
      second receptor chain are still unknown. It has also been shown that in the case
      of IL-19 and IL-20, IL-20R2 rather than IL-20R1 is a high-affinity receptor
      chain. This review summarizes all published three-dimensional structures of the
      cytokines representing the IL-10 family of homologs, including the IL-19
      subfamily and their interaction with appropriate receptors.

PMID- 15579077
TI  - Lymnaea EGF and gigantoxin I, novel invertebrate members of the epidermal growth
      factor family.
AB  - In this review, we compare the sequence and structural relationships of two
      epidermal growth factor (EGF) family related proteins that have recently been
      discovered in invertebrate species. The first is L-EGF, a secreted growth factor
      from the gastropod mollusk Lymnaea stagnalis. The second is a peptide toxin
      (Gigantoxin I), isolated from the sea anenome Stichodactyla giganteus, which can
      paralyze crabs. L-EGF and Gigantoxin I share striking sequence similarity with
      mammalian erbB1 receptor ligands, including most of the essential receptor
      binding sites. Intriguingly, L-EGF's tertiary structure resembles more the
      structure of the EGF-like domain of coagulation factors. That is, the secondary
      and tertiary structure of L-EGF indicates the presence of a double-stranded beta
      sheet but also suggests that this protein, in contrast to all other erbB1
      ligands, contains a calcium-binding domain. One of the most remarkable features
      of L-EGF and Gigantoxin I however, is the indication that these protein are
      synthesized as non-membrane bound secreted peptides. This feature sets L-EGF and
      Gigantoxin I apart from all other members of the EGF family or EGF-like proteins
      identified thus far. We discuss sequence similarities and dissimilarities in the
      light of indications that, despite the more than 600 million years of
      phylogenetic distance separating both these invertebrates from mammals,
      Gigantoxin I and L-EGF retain some affinity for the mammalian erbB-family of
      receptors. Considering that mammalian EGF and its family members are frequently
      implicated in neoplastic diseases, the increasing number of identified and
      characterized invertebrate EGF family members may provide valuable leads in the
      design of erbB receptor antagonists.

PMID- 15579078
TI  - Mollusk-derived growth factor and the new subfamily of adenosine deaminase
      related growth factors.
AB  - Peptide and protein growth factors play critical roles in the control of
      proliferation, differentiation and survival of most, if not all, cell types. In
      this review, we describe a newly isolated growth factor from Aplysia californica,
      mollusk derived growth factor (MDGF), that is a member of the adenosine deaminase
      related growth factor (ADGF) subfamily. Other known subfamily members from a
      range of invertebrate and vertebrate species include: insect-derived growth
      factor, Drosophila ADGFs, tsetse salivary growth factors, insect adenosine
      deaminases (ADAs; Lutzomyia, Culex, Aedes, Anopheles), and cat eye syndrome
      critical region gene 1 (CECR1) in humans, pigs, and zebrafish. ADGFs from
      vertebrates and invertebrates contain both an ADA domain and a novel N-terminal
      region of about 100 amino acids. Catalytic residues involved in ADA activity are
      conserved in ADGFs, and inhibitors of ADA can block ADGF activity. ADA enzymatic
      activity has been shown, by inhibitor and site-directed mutagenesis studies, to
      be related to the ability of ADGFs from many species to stimulate cell
      proliferation. The available evidence suggests that the conversion of adenosine
      to inosine (or their analogs) is important for the mitogenic actions of ADGFs.
      Future investigations of this novel subfamily should lead to the identification
      of their receptors.

PMID- 15579079
TI  - Common structural stability properties of 4-helical bundle cytokines: possible
      physiological and pharmaceutical consequences.
AB  - Biological activity and clinical efficacy of a therapeutic protein are contingent
      upon the structural stability, bioavailability, and clearance rates of the
      protein. In this review, we examine the class of 4-helical bundle cytokines for
      common stability properties that may affect biological structure and efficacy.
      Three critical stability features that are hallmarks of this class of cytokines
      are the pH dependence of structural stability, the presence of folding
      intermediates, and the population of aggregation intermediates. We hypothesize
      that certain cytokines have increased stability in acid to enable receptor
      mediated clearance, and that reengineering local endocytic trafficking can result
      in dramatic improvements in global serum half-life and therapeutic efficacy. The
      common feature of folding and aggregation intermediates has implications on
      kinetic folding pathways, membrane permeability, solubility, and precipitation
      properties that are critical for commercial production, formulation, and
      delivery. Understanding the structural stability properties of this class of
      cytokines may help elucidate new approaches to improving therapeutic efficacy.

PMID- 15579080
TI  - Structural basis and therapeutic implication of the interaction of CCN proteins
      with glycoconjugates.
AB  - The CCN family of growth factors is composed of six structurally related proteins
      including the cysteine-rich 61 (Cyr61), connective tissue growth factor (CTGF),
      nephroblastoma overexpressed (NOV), Wnt-1 induced secreted protein-1 (WISP-1),
      WISP-2 and WISP-3. Each family member consists of four conserved cysteine rich
      modular domains with sequence similarity to the insulin like growth factor
      binding proteins, von Willebrand factor, thrombospondin repeat and the growth
      factors cysteine knot. The CCN proteins demonstrate a wide variety of biological
      activities regulating cell adhesion, proliferation, survival, migration, invasion
      in vitro and tumorigenesis and angiogenesis in vivo. Both cancer promoting and
      inhibiting roles were proposed for several CCN proteins suggesting that
      contextual factors could regulate their activities. Consistent with this
      hypothesis, structural and experimental evidence indicate that the function of
      these proteins is modulated by their interaction with sulfated
      glycosaminoglycans. Because the CCN proteins are implicated in the tumorigenic
      process, they are potential targets for the development of cancer therapeutics.
      Modulation of their glycosaminoglycan interaction by exogenous, highly sulfated
      polysaccharides, oligosaccharides or glycosaminoglycan mimetics could prevent
      their participation in cancer progression. Understanding the structural
      requirements for their polysaccharide interaction should provide important
      information to generate glycosaminoglycan-based cancer therapeutics targeting the
      CCN family of proteins.

PMID- 15579081
TI  - Pharmaceutical care: past, present and future.
AB  - Since the concept of Pharmaceutical Care was introduced from United States about
      twenty years ago, this initiative has become a dominant form of practice for
      thousands of pharmacists around the world. Currently, pharmaceutical care is
      understood as the pharmacists' compromise to obtain the maximum benefit from the
      pharmacological treatments of the patients, being therefore responsible of
      monitoring their pharmacotherapy. As the profession has moved from a product
      orientation (dispensing medications) to a patient focus, clinical training
      requirements have expanded. This is a slow but ongoing process, which started
      from a philosophical point of view, in order to transform the concept of Pharmacy
      from commodity-based, mercantile operations into a clinical profession in the
      community pharmacies. Since its introduction, there has been an ample debate on
      the definition of pharmaceutical care due to differences in Pharmacy systems and
      in health care structure among the different countries. Moreover, several
      implementation barriers exist, which are attributable to problems in education,
      skills, resources and environment. Indeed, an awareness of the problem resulting
      from the use of medicines exists and numerous studies reflect that drug use
      control is necessary since there is an important relationship between morbidity /
      mortality and pharmacotherapy. Thus, it is possible to evaluate the benefits of
      pharmaceutical care on patients' health and ultimately on society. Many studies
      have been conducted, which show that the provision of pharmaceutical care has its
      value in common pathologies such as diabetes, hypertension, asthma,
      hyperlipidemia, chronic pain, rheumatic diseases or psychiatric disorders, as
      well as in polymedicated patients. A large amount of data is currently being
      published in biomedical journals, in an effort to establish the clinical,
      economic and humanistic viability of pharmaceutical care. Thus, the aim of this
      review is to study the evolution of this practice from its beginning until
      nowadays. Furthermore, we have analyzed a number of implementation programs
      performed in countries of Europe, the United States and Latin America, focusing
      on clinical, economical and humanistic outcomes, and also, on the current concept
      of drug therapy problems (DTP) considered as failures in drug therapy. We
      conclude that the positive outcomes obtained with different programs of
      pharmaceutical care are making a beneficial change in patients' health but still
      more research projects should be conducted to support this change.

PMID- 15579082
TI  - Morbidity and mortality associated with pharmacotherapy. Evolution and current
      concept of drug-related problems.
AB  - Medicines are a great contribution to the rising life expectancy in XX century.
      But a lot of drug safety problems were reported since 1960's. More recently,
      ineffectiveness is also being considered as a problem. Since 1975, the term 'drug
      related problem' (DRP) is being used for several definition and purposes. This
      has led to a number of different DRP classifications. The aim of the present
      review is to gather different positions, definitions and classifications of DRP.
      And to present a more modern concept, which is also named as pharmacotherapy
      failure, corresponding to negative clinical outcomes resulting from the use or
      the lack of use of medicines. Those pharmacotherapy failures include necessity,
      effectiveness and safety problems.

PMID- 15579083
TI  - Structural process and implementation programs of pharmaceutical care in
      different countries.
AB  - Pharmaceutical care started in the nineties in the United States and has rapidly
      extended in many other countries. Although there are different trends, such as
      clinical pharmacy services, cognitive services, medication management, medication
      review, they all share the same philosophy and objectives, namely "the
      responsible provision of drug therapy for the purpose of achieving definite
      outcomes that improve a patient's quality of life". To attain these objectives, a
      pharmaceutical care process has to be followed point-by-point in order to detect
      possible medication-related problems. Furthermore, pharmacists have to work
      together with patients, and ultimately with physicians to establish a care plan.
      This methodology requires basic skills of documentation and communication and
      therefore, it is important to establish implementation programs aimed at
      community-, hospital-, and consultant pharmacists, and to consider PC as a basic
      element of University teaching programs and postgraduate studies. Moreover, there
      are still barriers that hinder the provision of this service and have to be
      overcome. In this article, we have revised the implementation process and the
      existing projects in many countries and we conclude that despite the enormous
      amount of work, there is still much to be done from sides of Administration and
      pharmacists themselves.

PMID- 15579084
TI  - The impact of pharmaceutical care practice on the practitioner and the patient in
      the ambulatory practice setting: twenty-five years of experience.
AB  - This manuscript reviews 25 years of experience that include developing the
      practice of pharmaceutical care and initiating new practices. The impact this
      practice has on practitioners in the ambulatory setting is described as well as
      data that reflect its clinical and economic impact. There is a great need to
      prepare new practitioners to provide pharmaceutical care. A focused training
      program was developed and delivered to over 300 practitioners. The practitioners
      were prepared by providing direct patient care. They learned the philosophy of
      pharmaceutical care practice, to identify, resolve and prevent drug therapy
      problems, to document care using a specially designed software program called the
      Assurance Pharmaceutical Care program. The practitioners who participated in the
      training program reported that the average amount of time spent with patients
      increased three-fold, they now see four times more patients than prior to
      training, and the number of new patients referred by physicians increased nine
      fold as a result of the program. These practitioners have now provided care to
      more than 25,000 patients in their practices. These data have now been
      consolidated and analyzed, and a portion of these results is reported here. The
      clinical and economic outcomes from 2,985 adult patients, who received
      pharmaceutical care between January, 2000 and December, 2003, are presented. At
      the first assessment by the pharmaceutical care practitioner, 61% of the patients
      had one or more drug therapy problems identified and resolved. This resulted in
      an improvement in the clinical status or maintaining a stable status in 83% of
      the patients. The health care savings realized from pharmaceutical care were
      $1,134,162. This represented a benefit to cost ratio of 2:1. Physicians who
      collaborate with pharmaceutical care practitioners have validated the work of the
      practitioners, and patients are recognizing the benefits of pharmaceutical care.

PMID- 15579085
TI  - Anti-HIV drug development--an overview.
AB  - Highly active antiretroviral therapy (HAART) has markedly decreased mortality and
      morbidity in the developed world. HAART consists of a combination of three or
      more of the following classes of antiretroviral (ARV) drug: reverse transcriptase
      inhibitors, protease inhibitors and a recently approved fusion inhibitor.
      However, HAART cannot completely eradicate HIV from the body, results in long
      term toxicity and eventually leads to the emergence of drug-resistant HIV
      strains. These problems prompt the search for potent new drugs that are active
      against drug-resistant viral strains and that can safely be combined with other
      ARV drugs. The aim of this review was to give an overview of new compounds in
      preclinical or early clinical development that interact with various steps in the
      HIV life cycle: virus-cell attachment; gp120-CD4 binding; gp120-coreceptor
      binding; viral fusion; viral assembly and disassembly; reverse transcription;
      nuclear import of the pre-integration complex; proviral integration; viral
      transcription; processing of viral transcripts and nuclear export; assembly of
      new virions; cellular factors involved in HIV replication.

PMID- 15579086
TI  - Action of anti-HIV drugs and resistance: reverse transcriptase inhibitors and
      protease inhibitors.
AB  - Currently, 20 drugs have been approved for Human Immunodeficiency Virus type-1
      (HIV-1) clinical therapy. These drugs inhibit HIV-1 reverse transcriptase,
      protease, or virus entry. Introduction of a combination therapy with reverse
      transcriptase inhibitors and protease inhibitors has resulted in a drastic
      decrease in HIV-1 related mortality. Although the combination therapy can
      suppress viral replication below detection levels in current available assays,
      low levels of on-going viral replication still persist in some patients. Long
      term administration of the combination therapy may increase selective pressure
      against viruses, and subsequently induce emergence of multiple drug-resistant HIV
      1 variants. Attempts have been made to design novel antiretroviral drugs that
      would be able to suppress replication of the resistant variants. At present,
      several investigational drugs are being tested in clinical trials. These drugs
      target not only the resistant variants, but also improvement in oral
      bioavilability or other viral proteins such as HIV-1 integrase, ribonuclease H,
      and HIV-1 entry (CD4 attachment inhibitors, chemokine receptors antagonists, and
      fusion inhibitors). Understanding mechanism(s) of action of the drugs and
      mechanisms of drug resistance is necessary for successful designs in the next
      generation of anti-HIV-1 drugs. In this review, the mechanisms of action of
      reverse transcriptase- and protease-inhibitors, and the mechanism of resistance
      to these inhibitors, are described.

PMID- 15579087
TI  - Acquisition of multi-PI (protease inhibitor) resistance in HIV-1 in vivo and in
      vitro.
AB  - Protease inhibitors are effective antiviral agents which can lead to a severe
      decrease in HIV RNA copies in plasma of naive patients, however even successful
      suppression of the virus with antiretroviral agents including protease
      inhibitor(s) (PI(s)) generates PI-resistant HIV-1 after long term treatment.
      Occasionally HIV-1 acquires cross-resistance to other PIs with which the patients
      have not been treated. Cross-resistance to multiple PIs (multi-PI resistance)
      leads to a restricted salvage strategy; therefore multi-PI resistance is one of
      the serious obstacles to efficient antiretroviral chemotherapy. The most common
      PI-resistance mechanism in HIV-1 is the emergence and accumulation of multiple
      amino acid substitutions within the viral protease. As well, additional
      substitutions in protease cleavage sites or substitutions in the Gag protein at
      non-cleavage sites are involved in recovery of the reduced replication fitness of
      HIV-1 caused by these mutations in the viral protease. To address or predict the
      resistance mechanisms of PIs, resistant HIV-1 variants have been intensively
      studied in vitro. However, the profiles of the amino acid substitutions obtained
      in PI resistant variants are more diverse and complex than that found in vitro.
      More elaborate in vitro systems for further analysis of acquisition of PI
      resistance mechanisms are needed.

PMID- 15579088
TI  - Drug resistance, virus fitness and HIV-1 mutagenesis.
AB  - The evolution of antiretroviral drug resistance is a major problem in the
      treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy
      failure is associated with accumulation of drug resistance mutations and results
      in the development of drug resistance. Drugs targeted against reverse
      transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1
      mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can
      increase virus mutation frequencies in a multiplicative manner. The evolution of
      drug resistance also alters virus fitness. The correlation of increased HIV-1
      mutation rates with the evolution of antiretroviral drug resistance indicates
      that drug failure could increase the likelihood of further resistance evolving
      from subsequent drug regimens. These observations parallel studies from microbial
      systems that provide evidence for a correlation between drug resistance
      development and increased pathogen mutation rates. Although increased mutant
      frequencies may be detrimental to effective therapy, the lethal mutagenesis of
      the HIV-1 genome may provide a new means for antiretroviral therapy.

PMID- 15579089
TI  - Antiretroviral drugs and the kidney: dosage adjustment and renal tolerance.
AB  - BACKGROUND: Acquired immunodeficiency syndrome (AIDS)-related kidney disorders
      concern 30% of those patients and can lead to end-stage renal disease (ESRD; 0.6
      to 1%). Therefore, administration of antiretroviral drugs in human
      immunodeficiency virus (HIV) patients with nephropathy is not uncommon. AIM OF
      THE REVIEW: Since renal insufficiency is not uncommon among HIV-infected patients
      treated with antiretroviral drugs, guidelines on how to use these drugs in the
      pattern of an altered renal function are mandatory. This review provides such
      guidelines established on the basis of pharmacokinetic and clinical studies
      reported in the international literature. In addition, some of these drugs may be
      nephrotoxic. Mechanisms and clinical and/or biological manifestations are
      reviewed to help monitor renal tolerance in patients receiving these drugs.
      CONCLUSION: Antiretroviral drugs' dosage in HIV-infected patients with altered
      renal function should be cautiously determined. Drug dosage should not be
      systematically reduced since dosage adjustment is not mandatory for all therapies
      (ie. protease inhibitors). Furthermore, when dose reduction is necessary,
      pharmacokinetic and clinical data from the literature allows to establish
      practical guidelines on how to use these drugs in such patients.

PMID- 15579090
TI  - Antiviral drugs that target cellular proteins may play major roles in combating
      HIV resistance.
AB  - Despite the significant progresses made in antiretroviral therapy, current drugs
      still cannot cure or prevent HIV infection. And all drugs continue to select for
      drug-resistant HIV strains. Consequently, new antiretroviral drugs are constantly
      being developed. To ensure safety, these drugs are usually designed to inhibit
      viral proteins. But cellular proteins are also emerging as potential targets for
      new antiretroviral drugs. Two drugs that target cellular proteins inhibit HIV
      replication in vitro, hydroxyurea (HU) and pharmacological cyclin-dependent
      kinase inhibitors (PCIs). HU has been tested in clinical trials, commonly in
      combination therapies. PCIs, which are newer drugs, have just started to be
      tested in animal models of HIV-induced disease. Herein, we will review the HIV
      replication cycle and discuss the biological causes why strains resistant to
      antiviral drugs are so easily selected for. We will then discuss current
      antiretroviral drugs and HU before focusing on PCIs. PCIs have demonstrated to be
      effective against wild-type and drug-resistant strains of HIV in vitro, while
      selecting for no drug resistance. PCIs are additive with conventional antiviral
      drugs against herpes simplex virus, which suggests that they could also be
      additive with antiretroviral drugs. Since PCIs are proving surprisingly safe in
      human clinical trials (against cancer), they may be developed as clinical
      antiretroviral drugs in the near future. Recent and exciting studies indicate
      that PCIs ameliorate the pathogenesis of an animal model of HIV-induced
      nephropathy. We can expect that the full potential of PCIs as antiretroviral
      drugs will be explored in the coming years.

PMID- 15579091
TI  - "Virostatics" as a potential new class of HIV drugs.
AB  - The combination of three or more antiretroviral drugs is referred to as highly
      active antiretroviral therapy (HAART) and constitutes the standard of care for
      HIV-1 patients in industrialized nations. Although HAART is usually effective in
      reducing viral load and re-constituting CD4 counts, latent virus reservoirs
      persist, and as many as 60 years therapy [1, 2] may be required to eradicate the
      virus. Meanwhile, patients are likely to experience drug related toxicity and may
      have to change therapy due to the emergence of drug resistant strains. For these
      reasons, the search for different therapeutic approaches continues. A new concept
      of antiviral/cytostatic ("virostatics") drugs has been proposed within the
      context of HAART to restrict virus target populations (CD4(+) T lymphocytes),
      target viral reservoirs, and possibly restore immune functions, by reducing
      excess immune activation, a fundamental component of HIV/AIDS pathogenesis. These
      virostatics include drugs such as hydroxyurea, mycophenolic acid, leflunomide and
      rapamycin, which are currently used for other therapeutic indications; and other
      experimental drugs, which are not for human use. They utilize multiple novel
      mechanisms of action to impede HIV by targeting host cellular proteins that are
      not susceptible to mutation. Therefore, their resistance profile appears to be
      quite favorable. Since many of these drugs act by inhibiting the synthesis of
      deoxynucleotides, essential for HIV reverse transcription, they favor the
      incorporation of nucleoside analogues into viral DNA, thus synergizing with the
      antiviral activity of currently used nucleoside reverse transcriptase inhibitors
      (NRTI). The rationale for the use of virostatics in HIV/AIDS, their mechanism of
      action, and ongoing preclinical and clinical research will be reviewed.

PMID- 15579092
TI  - Cellular physiology of mismatch repair.
AB  - The DNA mismatch repair system maintains genomic stability by correcting DNA
      sequence errors generated during DNA replication, during genetic exchanges
      between chromosomes i.e., recombination, and by correcting DNA lesions caused by
      mutagenic agents such as cis-platinum. Post-synthesis mismatch repair improves
      almost 1000-fold the fidelity of DNA replication; however, the functions of
      mismatch repair proteins extend well beyond DNA repair. Recent studies suggest
      that mismatch repair is part of the machinery that couples DNA damage and repair
      to cell cycle regulation and apoptosis. These studies indicate that tolerance to
      certain DNA lesions (such as methylation and cis-platinum adducts) is associated
      with inefficient activation of cell cycle checkpoints and inefficient activation
      of apoptosis in mismatch repair deficient cells. Hence, mismatch repair proteins
      regulate the survival threshold to DNA damage, and this function provides a novel
      platform for understanding the role of mismatch repair in B cells, in tumor
      formation, as well as in resistance to chemotherapy. In this communication, we
      review how mismatch repair may contribute to the physiology of cells and may be
      regulated by the intracellular trafficking of mismatch repair proteins.

PMID- 15579093
TI  - Current biological therapies for inflammatory bowel disease.
AB  - Current biological therapies for inflammatory bowel disease reflect the
      exponential advancement in understanding the human intestinal immune system and
      particularly the biology of intestinal inflammation over the past decade. The
      better understanding of the mechanisms of inflammatory bowel disease has evolved
      from descriptive clinical data and genetically engineered animal models. It led
      to great interest in a variety of new therapeutic agents and procedures with
      novel actions. This review will discuss the mechanisms of biologics (antibodies
      against pro-inflammatory cytokines, T-cell antibodies, anti-inflammatory
      cytokines, adhesion molecule blockers, growth factors, colony stimulating
      factors, fusion proteins, anti-sense oligonucleotides, hormones,
      immunostimulatory DNA (ISS-DNA, CpG Oligodeoxynucleotides) and parasites
      (Trichuris suis eggs), used in inflammatory bowel disease and summarize the
      available data on investigational and approved agents, and briefly touch on
      probiotics and extracorporeal immunomodulation (leukocyte apheresis and
      photoapheresis). Based on the data discussed, it appears that biologics may play
      an increasing role in managing inflammatory bowel disease in the near future.

PMID- 15579094
TI  - Ruthenium antimetastatic agents.
AB  - NAMI-A, i. e. (imH)[trans-RuCl(4)(dmso-S)(im)] (im = imidazole, dmso =
      dimethylsulfoxide), is a Ru(III) complex that, after extensive preclinical
      investigations that evidenced its remarkable and specific activity against
      metastases, has recently and successfully completed a Phase I trial (first
      ruthenium complex ever to reach clinical testing). This review article, after a
      brief summary of the main chemical and pharmacological aspects of NAMI-A, focuses
      on the development of new classes of ruthenium complexes originated from the NAMI
      A frame. In particular, the chemical and biological features of the following
      classes of compounds will be treated: i) NAMI-A-type complexes, derived from NAMI
      A by changing the nature of the N-ligand, ii) dinuclear NAMI-A-type compounds
      containing heterocyclic bridging N-N ligands, iii) new Ru-dmso nitrosyls broadly
      derived from NAMI-A-type complexes. Several of these new compounds were found to
      have antimetastatic activity comparable to, or even better than, NAMI-A; however,
      the nature of the target(s) responsible for the antimetastatic activity remains
      unclear. Common to any type of NAMI-A-type compound, both monomeric and dimeric,
      cell cytotoxicity (which is generally very low) is not sufficient to explain
      their potent and peculiar antitumor activity. All active NAMI-A-type compounds
      share the capacity to modify important parameters of metastasis such as tumor
      invasion, matrix metallo proteinases activity and cell cycle progression.

PMID- 15579095
TI  - Platinum-intercalator conjugates: from DNA-targeted cisplatin derivatives to
      adenine binding complexes as potential modulators of gene regulation.
AB  - Nuclear DNA is the cellular target for many cancer treatments, and DNA-directed
      chemotherapies continue to play an important role in drug discovery in the
      postgenomic era. The majority of DNA-targeted anticancer agents bind through
      covalent interactions, non-covalent intercalation or groove binding, or hybrid
      binding modes. The sequence and regiospecificity of these interactions and the
      resulting structural alterations within the biopolymer play an important role in
      the mechanism of action of these drugs. DNA-binding proteins and/or DNA
      processing enzymes, which also interact with DNA in a sequence- and groove
      specific manner, are mediators of the cytotoxic effect produced by these agents.
      Thus one major goal in the design of new clinical agents of this type is to
      produce new types of adducts on DNA, which may lead to unprecedented cell kill
      mechanisms. Platinum-intercalator conjugates are such a class of hybrid agents
      acting through a dual DNA binding mode. The platinum center (usually a cis
      diaminedichloroPt(II) unit) dominates the DNA adduct profiles in the majority of
      these species-the result of the metal's tendency to form cross-links in runs of
      consecutive guanine bases in the major groove of DNA. This paradigm has been
      broken recently for the first time with the design of cytotoxic platinum
      acridinylthiourea conjugates, a class of adenine-affinic minor-groove directed
      agents. This review summarizes major advancements in the chemistry and biology of
      platinum-intercalators from 1984 to 2004, with emphasis being placed on the
      interplay between chemical structure, mechanism of DNA binding, and biological
      properties.

PMID- 15579096
TI  - A bioinorganic perspective on matrix metalloproteinase inhibition.
AB  - The zinc-dependent enzymes known as matrix metalloproteinases (MMPs) are
      medicinal targets due to the activity of these enzymes associated with diseases
      such as cancer, heart disease, and arthritis. The development of most MMP
      inhibitors (MPIs) has followed a basic design formula: a peptidomimetic backbone
      is attached to a zinc-binding group (ZBG). MPI backbones have varied enormously
      and improved with increased knowledge of MMP structure and function while
      hydroxamic acids have been used as the ZBG in most inhibitors. The problems
      associated with hydroxamic acid and other current ZBGs have been identified; the
      incorporation of more potent and selective ZBGs for the active site zinc(II) ion
      is necessary to improve the development of second-generation inhibitors. Herein,
      we highlight ZBGs that have been proposed as alternatives to hydroxamic acids. In
      addition, techniques used to identify new ZBGs are also discussed. New insights
      from a bioinorganic approach using model complexes of the MMP active site are
      presented as tools in examining the mode of binding for various known and novel
      ZBGs. Novel computational methods are highlighted that allow for modeling the
      drug-protein interactions with non-hydroxamate inhibitors of MMPs. We suggest
      that significant efforts to augment ZBGs combined with the available information
      on inhibitor backbone design will accelerate the discovery of improved MPIs.
      Newly devised drug design methods will help to realize this proposal.

PMID- 15579097
TI  - Gallium in cancer treatment.
AB  - The trivalent gallium cation is capable of inhibiting tumor growth, mainly
      because of its resemblance to ferric iron. It affects cellular acquisition of
      iron by binding to transferrin, and it interacts with the iron-dependent enzyme
      ribonucleotide reductase, resulting in reduced dNTP pools and inhibition of DNA
      synthesis. The abundance of transferrin receptors and the up-regulation of
      ribonucleotide reductase render tumor cells susceptible to the cytotoxicity of
      gallium. Remarkable clinical activity in lymphomas and bladder cancer has been
      documented in clinical studies employing intravenous gallium nitrate, which is
      currently being re-evaluated in non-Hodgkin's lymphoma. An improved therapeutic
      index is expected to result from prolonged exposure to low steady-state plasma
      gallium levels. Attempts to accomplish this by oral administration of gallium
      chloride failed because of insufficient intestinal absorption. Complexation of
      gallium with ligands, which stabilize gallium against hydrolysis and facilitate
      membrane permeation, has been recognized as a promising strategy for overcoming
      these limitations. Two such gallium complexes, namely tris(3-hydroxy-2-methyl-4H
      pyran-4-onato)gallium(III) (gallium maltolate) and tris(8
      quinolinolato)gallium(III) (KP46), which both exhibit high bioavailability when
      administered via the oral route, are currently being evaluated in the clinical
      setting.

PMID- 15579098
TI  - Ruthenium as an effective nitric oxide scavenger.
AB  - Whilst nitric oxide (NO) has emerged as one of the most versatile and ubiquitous
      molecules in the human body with a diverse range of physiological functions,
      dysfunction in NO biosynthesis or metabolism has led to the pathogenesis of a
      number of disease states. A variety of therapeutic strategies have therefore
      emerged that either reduce or increase endogenous NO levels depending on the
      disease pathology. The predominant strategy to date to reduce levels of NO is to
      utilise specific isoform selective inhibitors of nitric oxide synthases, the
      enzymes responsible for NO biosynthesis. An alternative line of attack, not
      related to specificity for a particular enzyme, but rather on compartmental
      localisation and pharmacokinetics, is to remove or scavenge the excess NO
      responsible for the disease pathology. In this regard, a number of NO scavenger
      molecules have demonstrated pharmacological activity across a broad spectrum of
      disease states. This review will highlight the rationale behind the development,
      and the current state of play, of one such class of NO scavengers, complexes of
      the d-block transition metal ruthenium. Prior to this, a brief overview of the
      remarkable diversity of NO, both from a chemical and biological viewpoint, will
      be provided for perspective.

PMID- 15579099
TI  - The HIV-1 nucleocapsid zinc finger protein as a target of antiretroviral therapy.
AB  - Despite advances made in its therapeutic management, human immunodeficiency virus
      (HIV) infection has remained an intractable problem, and complete eradication of
      the virus an unrealized goal. Experience in the clinical application of
      combination therapy using a variety of reverse transcriptase and protease
      inhibitors have revealed a number of challenges, in spite of the observed albeit
      temporary success in reduction of patient viral loads. Problems with current
      protocols include poor patient compliance, and the presence of latent reservoirs
      of virus that ultimately result in the appearance of phenotypic resistance. These
      considerations necessitate continued research and development into alternative
      strategies to circumvent the aforementioned problems. One approach to minimizing
      and/or eliminating the appearance of escape mutants and latent viral reservoirs
      is the targeting of essential and mutationally intolerant enzymes such as the
      nucleocapsid protein, which contains two highly conserved zinc knuckles. Concerns
      have been raised regarding the targeting of this protein, since the ubiquitous
      occurrence of important mammalian zinc finger proteins implies that drug
      specificity towards the nucleocapsid protein may be difficult to attain. In this
      review, strong evidence supporting the hypothesis that this protein can be
      targeted to the exclusion of other cellular zinc finger proteins is presented.
      The effects of small molecule induced abrogation of nucleocapsid protein mediated
      activities, as well as efforts to develop nucleocapsid protein inhibitors as
      antiretrovirals are also discussed.

PMID- 15579100
TI  - Iron chelators in cancer chemotherapy.
AB  - Iron chelators may be of value as therapeutic agents in the treatment of cancer.
      They may act by depleting iron, a necessary nutrient, and limiting tumor growth.
      Alternatively or additionally, they may form redox-active metal complexes that
      cause oxidative stress via production of reactive oxygen species, damaging
      critical intracellular targets and thereby eliciting a cytotoxic response.
      Studies in vitro have evaluated the structure-activity relationships and
      mechanism of action of many classes of iron chelators, including desferrioxamine
      (DFO), pyridoxal isonicotinoyl hydrazone (PIH) analogs, desferrithiocin (DFT)
      analogs, tachpyridine, the heterocyclic carboxaldehyde thiosemicarbazones, and O
      Trensox. Animal studies have confirmed the antitumor activity of several
      chelators. Dexrazoxane has been approved for use in combination with doxorubicin,
      and its effectiveness in allowing higher doses of doxorubicin to be administered
      is, in part, based on the interactions of both drugs with iron. Clinical trials
      of the antitumor activity of chelators have been largely limited to DFO, which
      has been extensively studied as a consequence of its approved use for treatment
      of secondary iron overload. While the modest antitumor effects of DFO are
      encouraging, it is likely that more effective iron chelators may be identified.

PMID- 15579101
TI  - Metalloenediynes: advances in the design of thermally and photochemically
      activated diradical formation for biomedical applications.
AB  - The remarkable discovery of the enediyne antitumor antibiotics almost two decades
      ago has led to significant developments in the systematic design and study of
      simple synthetic enediyne constructs and their Bergman cyclization reactivities.
      Advances in understanding both the geometric and electronic factors that are
      important in influencing the activation barrier to formation of the potent 1,4
      phenyl diradical intermediate in simple organic enediynes have been made as a
      first step to the development of synthetic agents for biomedical uses. Progress
      in these areas has also served as a benchmark and guideline for a new wave of
      inorganic metalloenediyne constructs that display variable and wide-ranging
      reactivity or stability depending upon the geometric or electronic structure of
      the resulting complex. In general, metal sites offer additional structural
      flexibilities over their carbocyclic or acyclic organic analogues, which
      contributes greatly to their intriguing Bergman cyclization reactivities. This is
      true not only for thermal cyclization of metal-bound enediyne ligands in which
      the metal acts as a scaffold or Lewis acid, but also for photoelectronic or
      photothermal Bergman cyclization which can be achieved via metal-ligand charge
      transfer excited states. These reactivity developments parallel new protein
      targeting strategies for simple enediynes constructs, suggesting that a combined
      approach of controlled initiation and site specific targeting may allow enediynes
      to truly reach their full potential in biomedical applications.

PMID- 15579102
TI  - Bridging the gap between structural bioinformatics and receptor research: the
      membrane-embedded, ligand-gated, P2X glycoprotein receptor.
AB  - MOTIVATION: No details on P2X receptor architecture had been known at the atomic
      resolution level. Using comparative homology-based molecular modelling and
      threading, it was attempted to predict the three-dimensional structure of P2X
      receptors. This prediction could not be carried out, however, because important
      properties of the P2X family differ considerably from that of the potential
      template proteins. This paper reviews an alternative approach consisting of three
      research fields: bioinformatics, structural modelling, and a variety of the
      results of biological experiments. MODEL: Starting point is the amino acid
      sequence. Using the sequential data, the first step is a secondary structure
      prediction. The resulting secondary structure is converted into a three
      dimensional geometry. Then, the secondary and tertiary structures are optimized
      by using the quantum chemistry RHF/3-21G minimal basic set and the all-atom
      molecular mechanics AMBER96 force field. The fold of the membrane-embedded
      protein is simulated by a suitable dielectricum. The structure is refined using a
      conjugate gradient minimizer (Fletcher-Reeves modification of the Polak-Ribiere
      method). The results of the geometry optimization were checked by a Ramanchandran
      plot, rotamer analysis, all-atom contact dots, and the C(beta) deviation. As
      additional tools for the model building, multiple alignment analysis and
      comparative sequence-function analysis were used. The approach is exemplified on
      the membrane-embedded, ligand-gated P2X3 receptor subunit, a monovalent-bivalent
      cation channel-forming glycoprotein that is activated by extracellular adenosine
      5'-triphosphate. From these results, a topology of the pore-forming motif of the
      P2X3 receptor subunit was proposed. It is believed that a fully functional P2X
      channel requires a precise coupling between (i) two distinct peptide modules, an
      extracellularly occurring ATP-binding module and a pore module that includes a
      long transmembrane and short intracellular part, (ii) an interaction surface with
      membranes, and (iii) hydrogen bonding forces of the residues and hydrated
      cations. Furthermore, this paper demonstrates the role of quantitative structure
      activity relationships (QSARs) in P2X research (calcium ion permeability of the
      wild-type and after site-directed mutagenesis of the rat P2X2 receptor protein,
      KN-62 analogs as competitive antagonists of the human P2X7 receptor).
      EXPERIMENTAL PROOFS: The predictions are experimentally testable and may provide
      an additional interpretation of experimental observations published in
      literature. In particular, there is the good agreement of the geometry optimized
      P2X3 structure with experimentally proposed P2X receptor models obtained by
      neurophysiological, biochemical, pharmacological, and mutation experiments.
      Although the rat P2X3 receptor subunit is more complex (397 amino acids) than the
      KcsA protein (160 amino acids), the overall folds of the peptide backbone atoms
      are similar. LIMITATIONS: To avoid semantic confusion, it should be noted that
      "prediction" is defined in a probabilistic sense. Matches to generic rules do not
      mean "this is true" but rather "this might be true". Only biological and chemical
      knowledge can determine whether or not these predictions are meaningful. Thus,
      the results from the computational tools are probabilistic predictions and
      subject to further experimental verification. AVAILABILITY: The geometry
      optimized P2X3 receptor subunit is freely available for academic researchers on e
      mail request (PDB format).

PMID- 15579103
TI  - Agonists and antagonists acting at P2X7 receptor.
AB  - The P2X(7) receptor is involved in several processes relevant to inflammation
      (cytokine release, NO generation, killing of intracellular pathogens,
      cytotoxicity), thus, it may be an appealing target for pharmacological
      intervention. The characterisation of native and recombinant P2X(7) receptor
      continues to be hindered by the lack of specific and subtype-selective agonists
      and antagonists. BzATP is currently the most potent agonist known at the
      endogenous and recombinant P2X(7) receptor A tyrosine derivative named KN-62
      exhibits selective P2X(7) receptor-blocking properties. In this review article we
      have reported novel series of KN-62-related compounds of the general structure
      R(1)-Tyr(OR(2))-piperazinyl-R(3), in which three positions (R(1), R(2) and R(3))
      were systematically varied. Two recent articles published by AstraZeneca have
      reported that novel series of cyclic imides and adamantane amides are potent
      P2X(7) receptor antagonists.

PMID- 15579104
TI  - Dissecting individual current components of co-expressed human P2X1 and P2X7
      receptors.
AB  - Purinergic P2X(1) and P2X(7) receptors are co-expressed in several cell types
      such as lymphocytes or epithelial cells. Here we examined whether these two P2X
      subtypes interact with each other in a manner that results in a mutual alteration
      of their electrophysiologic behaviour. Furthermore, since specific
      pharmacological tools are needed to assign distinct effects to a particular
      receptor subtype in native cells, we assessed a series of compounds for their
      capacity to separate individual current components in cells that co-expressed
      both receptor subtypes. In Xenopus oocytes, co-expression neither changed the
      time courses of activation, desensitization and deactivation nor recovery from
      desensitization when compared to oocytes that express either hP2X(1) or hP2X(7)
      receptors alone. A selective activation of hP2X(7) receptors was achieved with
      benzoyl-benzoyl-ATP, which did not activate P2X(1) receptor currents. P2X(7)
      receptors could also be selectively activated by ATP when co-applied with 1
      microM NF449, a suramin derivative, which is 100,000 fold more potent in blocking
      P2X(1) than P2X(7) receptors. alphabeta-methylene-ATP, a reportedly hP2X(1)
      receptor-specific agonist, as well as oxidized-ATP, brilliant blue or KN62,
      reported hP2X(7) receptor antagonists, were found to be ineffective in separating
      hP2X(1) receptor current from the P2X(7) current. The best way for a selective
      activation of the hP2X(1) receptor component in cells co-expressing the P2X(7)
      receptor is the application of low concentrations of ATP (< 1 microM) or the
      addition of Mg2+ when using higher concentrations of ATP.

PMID- 15579105
TI  - Pharmacogenetics of the cytochromes P450.
AB  - The cytochromes P450 are a family of heme-containing proteins with a major role
      in the oxidation of both xenobiotics (including prescribed drugs) and endogenous
      compounds. There are at least 57 human P450s (termed isoforms) which are all
      encoded by separate genes but only 10 of these contribute to drug metabolism,
      with the major contribution coming from only 3 isoforms, CYP3A4, CYP2D6 and
      CYP2C9. It is now well recognised that most cytochrome P450 genes are subject to
      genetic polymorphism and that therefore some individuals have sequence changes
      present that result in the production of an enzyme with altered catalytic
      activity or give rise to abnormal gene expression. This article describes the
      range of genetic polymorphisms now known to occur in the drug metabolizing
      cytochromes P450 with particular reference to their functional effects and the
      influence of ethnic origin on the frequency of variant alleles. The relevance of
      the various polymorphisms to drug response and toxicity is considered as well as
      the possibility that genotype for these polymorphisms may be a determinant for
      "personalized prescribing" in the future.

PMID- 15579106
TI  - Induction of cytochromes P450.
AB  - The induction of cytochromes P450 (CYPs) has been appreciated for some time but
      an understanding of the mechanisms involved has been poorly understood until
      recently. The discovery of the role of nuclear receptors such as the pregnane X
      receptor (PXR) and the constitutive androstane receptor (CAR) has provided a
      major trigger for research in this area. This work has provided an explanation
      for species differences in hepatic induction. The production of a PXR crystal
      structure in the presence and absence of known high affinity ligands has offered
      the possibility of predicting structures which may bind to the receptor and hence
      act as inducing agents in man. An improvement in the technology of hepatocyte
      culture, access to good quality human hepatocytes and the miniaturisation of
      cultured preparations has meant that the potential of this technique to predict
      induction in man has been realised. Molecular biological techniques have also
      proved essential in both the science and the quantitation of CYP induction. The
      use of transient transfection cell based systems coupled with reporter gene
      assays have meant that dose response curves can be generated for many chemicals.
      Assays have been developed to measure the increase of the corresponding CYP mRNAs
      in primary hepatocytes and some cell lines with a high degree of sensitivity and
      specificity (allowing the quantitation of closely related CYPs). Although CYP
      induction is not usually considered as a major drawback in drug development, the
      aim should be to eliminate or reduce the inducing effects of a new drug to a
      minimum. Thus, it is essential to increase our understanding of the complex
      mechanisms that regulate induction and to pay attention to both the dose and the
      physicochemical and structural properties of CYP inducing agents.

PMID- 15579107
TI  - Cytochromes P450 in the bioactivation of chemicals.
AB  - The initial view that the cytochrome P450 enzyme system functions simply in the
      deactivation of xenobiotics is anachronistic on the face of mounting evidence
      that this system can also transform many innocuous chemicals to toxic products.
      However, not all xenobiotic-metabolising cytochrome P450 subfamilies show the
      same propensity in the bioactivation of chemicals. For example, the CYP2C, 2B and
      2D subfamilies play virtually no role in the bioactivation of toxic and
      carcinogenic chemicals, whereas the CYP1A, 1B and 2E subfamilies are responsible
      for the bioactivation of the majority of xenobiotics. Electronic and molecular
      structural features of organic chemicals appear to predispose them to either
      bioactivation by one cytochrome P450 enzyme or deactivation by another.
      Consequently, the fate of a chemical in the body is largely dependent on the
      cytochrome P450 profile at the time of exposure. Any factor that modulates the
      enzymes involved in the metabolism of a certain chemical will also influence its
      toxicity and carcinogenicity. For example, many chemical carcinogens bioactivated
      by CYP1, on repeated administration, selectively induce this family, thus
      exacerbating their carcinogenicity. CYP1 induction potency by chemicals appears
      to be determined by a combination of their molecular shape and electron
      activation. The function of cytochromes P450 in the bioactivation of chemicals is
      currently being exploited to design systems that can be used clinically to
      facilitate the metabolic conversion of prodrugs to their biologically-active
      metabolites in cells that poorly express them, such as tumour cells, in the so
      called gene-directed prodrug therapy.

PMID- 15579108
TI  - Crystallization of cytochromes P450 and substrate-enzyme interactions.
AB  - Our understanding of structure-function relationships have made considerable
      advances owing to the increasing number of new P450 crystal structures. This is
      especially true with mammalian P450s. As always, the main bottleneck in a
      structure determination project is crystallization. While the crystallization
      techniques used for P450 crystal growth are not much different from that utilized
      for other proteins, special protein engineering strategies have been developed in
      order to generate soluble, homogeneous membrane-bound P450 samples amendable for
      crystallization. Newly determined P450 structures also provide convincing
      evidence that P450 enzymes are highly dynamic and flexible. Common structural
      elements found in all P450s have been identified that undergo large
      conformational changes to allow substrate access and product release. In
      addition, flexible regions may enable the active site to adapt to the binding of
      substrates of different size, shape, and polarity. This review will focus on the
      successful membrane P450 crystallization techniques and the new structural
      insights based on the growing P450 structure database.

PMID- 15579109
TI  - In silico methods for predicting ligand binding determinants of cytochromes P450.
AB  - A large number of computational methodologies have been used to predict, and thus
      help explain, the metabolism catalysed by the enzymes of the cytochrome P450
      superfamily (P450s). A summary of the methodologies and resulting models is
      presented. This shows that investigations so far have focused on just a few of
      the many P450s, mainly those that are involved in drug metabolism. The models
      have evolved from simple comparisons of known substrates to more elaborate models
      requiring considerable computer power. These help to explain and, more
      importantly, predict the involvement of P450s in the metabolism of specific
      compounds.

PMID- 15579110
TI  - Decision support systems in drug discovery.
AB  - Decision support systems have been widely used in drug discovery owing to the
      complexity of data and information involved. In this article, we review both
      commercially available packages and publicized in-house made systems. All
      selected systems should be able to handle chemical structures and to organize
      information for decision makers, more specifically for medicinal chemists.
      Although we do not rank these system, pros and cons of these systems will be
      discussed.

PMID- 15579111
TI  - Computational techniques for diversity analysis and compound classification.
AB  - Molecular similarity and diversity analysis has played a significant role in
      computer-aided drug discovery for more than a decade. Compound classification
      methods have also become increasingly important for the design and organization
      of compound databases and in silico screening. Here we review these related
      methodologies and discuss selected applications.

PMID- 15579112
TI  - Physicochemical descriptors in property-based drug design.
AB  - The contribution of physicochemical descriptors to lipophilicity, water
      solubility, and intestinal absorption and oral bioavailability in humans is
      considered. Partitioning in the octanol/water system is presented as a
      competition between two opposing effects: volume and hydrogen bond acceptor
      ability. Water solubilities of liquid compounds are roughly equal to their
      reciprocal logP values. However, there is also a detectable contribution of H
      bond donor ability to water solubility. The main problem in predicting the
      solubilities of solid chemicals and drugs is the estimation of their crystal
      lattice energies. QSAR approaches that add terms such as melting point, and the
      product of H-bond donor and acceptor parameters are not sufficient to make these
      predictions practical. Human intestinal absorption for passively transported
      drugs is almost completely correlated with hydration processes that are
      determined by H-bond acceptor and donor abilities. It is emphasized that
      structural features of drug molecules have significant influences on their
      properties. Classic QSAR approaches are not enough to create stable, predictive
      models for diverse drugs. A combination of Similarity and QSAR approaches is one
      possibility to take all physicochemical properties in addition to structural
      features into account.

PMID- 15579113
TI  - Integration of virtual screening into the drug discovery process.
AB  - Advances in high-throughput virtual screening using docking, predictive ADME
      methods and their integration with informatics and high-performance computing are
      reviewed. Docking approaches have led to the identification of novel active
      compounds. Predictive ADME methods have improved on selective test sets with
      broader training sets, though extensive validation is lacking.

PMID- 15579114
TI  - Methods for library design and optimisation.
AB  - The introduction of combinatorial chemistry groups into pharmaceutical companies
      provoked a desire for efficient and effective methods for library design and
      optimisation. This, in turn, has resulted in a large number of scientific
      publications, detailing a variety of approaches to the problem. This review
      attempts to describe the major works in the literature, to set them in context
      both chronologically and scientifically, and to identify the outstanding
      challenges that must be addressed, if this area of research is to maintain the
      rapid progress seen hitherto.

PMID- 15579115
TI  - Microtubulin binding sites as target for developing anticancer agents.
AB  - Microtubules (MTs) play important and diverse roles in eukaryotic cells. Their
      function and biophysical properties have made alpha-and beta-tubulin, the main
      components of MTs, the subject of intense study. Interfering with normal MT
      dynamics, for example, by the addition of tubulin ligands, can cause the cell
      great distress and affect MT stability and functions, including mitosis, cell
      motion and intracellular organelle transport. It has been shown in the literature
      that tubulin is an important target molecule for developing anticancer drugs.
      Tubulin binding molecules have generated considerable interest after the
      successful introduction of the taxanes into clinical oncology and the widespread
      use of the vinca alkaloids vincristine and vinblastine. These compounds inhibit
      cell mitosis by binding to the protein tubulin in the mitotic spindle and
      preventing polymerization into the MTs. This mode of action is also shared with
      other natural agents eg colchicine and podophyllotoxin. However various tubulin
      isotypes have shown resistance to taxanes and other MT agents. Therefore, there
      is a strong need to design and develop new natural analogs as antimitotic agents
      to interact with tubulin at sites different from those of vinca alkaloids and
      taxanes. This minireview provides SAR on several classes of antimitotic agents
      reported in the literature. The structures and data given are essential to the
      scientists who are involved in drug design and development in the field of
      anticancer drugs.

PMID- 15579116
TI  - Synthetic approaches to the 2003 new drugs.
AB  - New drugs are introduced to the market every year and each individual drug
      represents a privileged structure for its biological target. In addition, these
      new chemical entities (NCEs) not only provide insights into molecular
      recognition, but also serve as drug-like leads for designing new future drugs. To
      these ends, this review covers the syntheses of 23 NCEs marketed in 2003.

PMID- 15579117
TI  - Effect of cyclodextrin on the activity and secondary structure of horseradish
      peroxidase.
AB  - The activity and secondary structure of horseradish peroxidase (HRP) was studied
      in aqueous solution containing alpha-, beta- and gamma-cyclodextrin (CD). The
      results showed that the activity of HRP was enhanced to different extents by the
      three kinds of CD. A Fourier Transform infrared (FTIR) spectroscopy study
      indicated that the amount of alpha-helical structure was important for the
      activity of HRP. This phenomenon is discussed.

PMID- 15579118
TI  - Content of the HMG-17 chromosomal protein in porcine tissues.
AB  - HMG-17 proteins are nucleosomal proteins, implicated in control of chromatin
      structure and transcription, in a way that has not yet been fully understood. In
      this report, quantification of HMG-17 in porcine tissues was performed, by ELISA,
      using previously produced and characterized specific rabbit anti-HMG-17
      antibodies. Our results showed high levels of HMG-17 compared to the DNA and H1
      content of the tissues (on the contrary to previous reports), and more
      specifically that there were 1.7 molecules of HMG-17 per molecule of histone H1.

PMID- 15579119
TI  - Interacting partners for kringle domains of plasminogen: common binding with K1
      and K5 domains.
AB  - We have identified MAZR and Rgl2 as specific interacting partners for kringle
      domains in angiostatin (K1-4) and K5 using yeast two hybrid screening. Both K1
      and K1-4 have strong interaction with MAZR and Rgl2 whereas K5 only binds with
      Rgl2. No interaction of K2, K3, and K4 with either of these binding proteins was
      detected. We suggest that a common binding motif may exist near LBS-4 that is
      required for binding with Rgl2 but not with MAZR.

PMID- 15579120
TI  - The relationship between the pY+3 amino acid in the phosphopeptide ligands and
      the specificity for various SH2 domains.
AB  - After consideration of the tertiary structure of the pY+3 binding pocket in SH2
      domains, isoleucine of Ac-pYEEIE was replaced with various unnatural aliphatic
      amino acids and the binding affinities for Lck, Src, and Fyn SH2 domains were
      measured. We determined the characteristics of the amino acid at the pY+3
      position in the phosphopeptide ligands for the specificity for the SH2 domains.

PMID- 15579121
TI  - Correlation between hydrophobicity sequence and accessibility sequence of
      membrane proteins.
AB  - In this paper, we used correlation analysis to quantify the correlations between
      the hydrophobicity sequence and accessibility sequence of 26 alpha-helix bundle
      membrane proteins and 119 transmembrane helices. Statistical significances of
      these correlations were also assessed. A slightly positive correlation was found
      in the alpha-helix bundle membrane proteins due to the contribution of extra
      membranous domains. No correlation was found in the transmembrane domains.

PMID- 15579122
TI  - Versatile synthesis of Boc protected hydrazinoacetic acid and its application to
      the chemoselective ligation of TASP molecules.
AB  - This paper describes a convenient synthesis of protected hydrazine derivatives,
      i.e. 1,2-bis-Boc-hydrazinoacetic acid, and its application for hydrazone ligation
      techniques in convergent template assembled synthetic protein (TASP) synthesis.

PMID- 15579123
TI  - Pressure stability of proteins at their isoelectric points.
AB  - Yeast alcohol dehydrogenase is slowly denatured at moderate hydrostatic pressure
      (t(1/2) approximately equals 30 min at 2 kbar and pH 7). The extent of
      denaturation is pH dependent with maximal stability near the isoelectric point of
      the protein, pH = 5.4. While not a surprising finding, it appears that this
      phenomenon has not been documented before (or at least not identified) despite
      many investigations into the pressure stability of proteins. Consideration of
      changes in the net charge of proteins far from their isoelectric points may
      explain other pressure effects as well.

PMID- 15579124
TI  - Synthesis of a shark repellent peptide toxin, Pardaxin (16-33) on a highly
      flexible polymer support: CLPSER.
AB  - A high swelling resin, CLPSER has been developed and utilized for the solid phase
      synthesis of Pardaxin, which is an 18-residue peptide. The resin was
      characterized by gel phase (13)C NMR, IR and SEM. The utility of the new polymer
      support in polypeptide synthesis was further established by the comparative
      synthesis of pardaxin with commercially available Merrifield resin. The MALDI TOF
      MS, amino acid analysis and the HPLC revealed the superior quality of CLPSER.

PMID- 15579125
TI  - Modifications in the purification protocol of Celosia cristata antiviral proteins
      lead to protein that can be N-terminally sequenced.
AB  - Plants antiviral proteins are being used as anticancer agents and inhibit other
      viral diseases in humans. We modified the purification protocol of the two N
      terminally blocked antiviral glycoproteins, CCP-25 and CCP-27, purified from the
      leaves of Celosia cristata. This not only gave rise to single pure samples with
      few steps of purification but also resulted in N-terminally free proteins. The
      extra purity of the samples was analyzed by reverse phase HPLC. Deglycosylation
      studies of CCP-25 with PNGase F enzyme revealed that its asparagine or asparagine
      linked glycon contents are negligible. Partial N-terminal sequence of the CCP-25
      showed the sequence (ANDIS), which seems to be conserved among plant antiviral
      proteins.

PMID- 15579126
TI  - A sialic acid-specific lectin from the mushroom Paecilomyces Japonica that
      exhibits hemagglutination activity and cytotoxicity.
AB  - The mushroom Paecilomyces japonica, grown on the silkworm larvae, has been used
      in Asia as a nutraceutical, tea, and Chinese medicine. In the present study, a
      sialic acid-specific lectin has been purified from the mushroom P. japonica using
      affinity chromatography on a fetuin-agarose column. Electrophoretical analyses
      indicated that this lectin, designated P. japonica agglutinin (PJA), is an acidic
      protein with a molecular mass of 16 kDa, and has no intermolecular disulfide
      bonds. PJA induced hemagglutination activity in human ABO, mouse, rat, and rabbit
      erythrocytes. This activity was inhibited by sialic acid and sialoglycoproteins,
      but not by any other carbohydrates. PJA was stable at pH 4.0-8.0, and at
      temperatures below 55 degrees C. The activity of PJA was independent of EDTA and
      divalent cations. In addition, PJA exerts cytotoxic effects on the following
      cancer cell lines: human stomach cancer SNU-1, human pancreas cancer AsPc-1, and
      human breast cancer MDA-MB-231.

PMID- 15579127
TI  - Inter-residue spatial distance map prediction by using integrating GA with RBFNN.
AB  - The spatial ordering information of amino acid residue in protein primary
      sequence is an important determinant of protein three-dimensional structure. In
      this paper, we describe a radial basis function neural network (RBFNN), whose
      hidden centers and basis function widths are optimized by a genetic algorithm
      (GA), for the purpose of predicting three dimensional spatial distance location
      from primary sequence information. Experimental evidence on soybean protein
      sequences indicates the utility of this approach.

PMID- 15579128
TI  - Comparative gene expression study to identify genes possibly related to storage
      root formation in cassava.
AB  - Cassava storage roots result from swelling of adventitious roots by secondary
      growth. In the present study we aimed to gain insight into the molecular
      processes occurring during cassava storage root formation. We report a
      comparative gene expression study in adventitious and storage roots in order to
      identify genes possibly related to storage organ formation. Our results revealed
      five genes with higher expression levels in secondary xylem of storage roots than
      adventitious roots. Among them, the Mec1 gene coding for Pt2L4 glutamic acid-rich
      protein and a putative RING Zinc Finger and LEA protein genes were strongly
      induced in secondary xylem tissue.

PMID- 15579129
TI  - Studies on the interaction of papain with human placental cystatin by UV,
      fluorescence and CD spectroscopy.
AB  - The interaction of activated papain with low molecular weight cystatin (Mr 12500)
      purified from human placenta has been studied. Analysis of inhibition of
      caesinolytic activity of papain by cystatin showed stoichiometry of 1:1. Kinetic
      studies gave an inhibition constant (K(i)) value of 5.5 x 10(-8) M and
      association rate constant (K(+1)) value of 3.4 x 10(4) (M(-1) s(-1)). All
      spectroscopic studies showed conformational changes in both papain and cystatin
      on formation of complex. The data suggest perturbation of environment of aromatic
      residues and change of their native structure and conformation thereby shedding
      light on the behaviour of cystatins, especially interaction of placental cystatin
      with thiol protease inhibitors.

PMID- 15579130
TI  - Misfolded proteins and human diseases.
AB  - Though protein folding is a regular phenomenon inside the cellular milieu, slight
      differences in the folding pattern of proteins may lead to disease-causing forms.
      Many diseases have been identified that are caused by these misfolded
      macromolecules and a considerable amount of focus is still directed towards
      better understanding of the processes that lead to these misfolded structures.
      Further progress in the field of how soluble proteins begin to misfold and how
      resultant oligomers begin dysfunction offers exciting prospects for specific
      molecular intervention.

PMID- 15579131
TI  - Stability and cleavage conditions of (2-furyl)-L-alanine-containing peptides.
AB  - The furyl group of (2-furyl)-L-alanine-containing peptides obtained from Fmoc
      solid-phase synthesis is partially degraded to several by-products during the
      final TFA-mediated deprotection in the presence of cation scavengers such as
      ethanedithiol and propanedithiol. The major by-product corresponds to a bis
      dithioacetale formed after acidic hydrolysis of the furyl group. We examined
      several cleavage conditions and found that cleavage cocktails containing water
      and triisopropylsilane or 3,6-dioxa-1,8-octanedithiol (DODT) in trifluoroacetic
      acid are sufficient to minimize the side reaction.

PMID- 15579132
TI  - Pharmacokinetics of 1-nitrosomelatonin and detection by EPR using iron
      dithiocarbamate complex in mice.
AB  - The N-nitroso-derivative of melatonin, NOM (1-nitrosomelatonin), which has been
      demonstrated to be a NO* [oxidonitrogen*] donor in buffered solutions, is a new
      potential drug particularly in neurological diseases. The advantage of NOM, a
      very lipophilic drug, is its ability to release both melatonin and NO*, an easily
      diffusible free radical. In order to evaluate the distribution and the
      pharmacokinetics of NOM, [O-methyl-3H]NOM was administered to and followed in
      mice. A complementary method for monitoring NOM, EPR, was performed in vitro and
      ex vivo with (MGD)2-Fe2+ (iron-N-methyl-D-glucamine dithiocarbamate) complex as a
      spin trap. The behaviour of NOM was compared with that of GSNO (S
      nitrosoglutathione), a hydrophilic NO* donor. In the first minutes following [O
      methyl-3H]NOM intraperitoneal injection, the radioactivity was found in organs
      (6% in the liver, 1% in the kidney and 0.6% in the brain), but not in the blood.
      In both liver and brain, the radioactivity content decreased over time with
      similar kinetics reflecting the diffusion and metabolism of NOM and of its
      metabolites. Based on the characterization and the quantification of the EPR
      signal in vitro with NOM or GSNO using (MGD)2-Fe2+ complex in phosphate-buffered
      solutions, the detection of these nitroso compounds was realized ex vivo in mouse
      tissue extracts. (MGD)2-Fe2+-NO was observed in the brain of NOM-treated mice in
      the first 10 min following injection, revealing that NOM was able to cross the
      blood-brain barrier, while GSNO was not.

PMID- 15579133
TI  - Characteristics of glutamine metabolism in human precision-cut kidney slices: a
      13C-NMR study.
AB  - The metabolism of glutamine, a physiological substrate of the human kidney, plays
      a major role in systemic acid-base homoeostasis. Not only because of the limited
      availability of human renal tissue but also in part due to the lack of adequate
      cellular models, the mechanisms regulating the renal metabolism of this amino
      acid in humans have been poorly characterized. Therefore given the renewed
      interest in their use, human precision-cut renal cortical slices were incubated
      in Krebs-Henseleit medium (118 mM NaCl, 4.7 mM KCl, 1.18 mM KH2PO4, 1.18 mM
      MgSO4*7H2O, 24.9 mM NaHCO3 and 2.5 mM CaCl2*2H2O) with 2 mM unlabelled or 13C
      labelled glutamine residues. After incubation, substrate utilization and product
      formation were measured by enzymatic and NMR spectroscopic methods. Glutamate
      accumulation tended to plateau but glutamine removal and ammonia, alanine and
      lactate production as well as flux through GLDH (glutamate dehydrogenase)
      increased to various extents with time for up to 4 h of incubation indicating the
      metabolic viability of the slices. Valproate, a stimulator of renal glutamine
      metabolism, markedly and in a dose-dependent fashion increased ammonia
      production. With [3-13C]glutamine as a substrate, and in the absence and presence
      of valproate, [13C]glutamate, [13C]alanine and [13C]lactate accounted for 81 and
      96%, 34 and 63%, 30 and 46% of the glutamate, alanine and lactate accumulations
      measured enzymatically respectively. The slices also metabolized glutamine and
      retained their reactivity to valproate during incubations lasting for up to 48 h.
      These results demonstrate that, although endogenous metabolism substantially
      operates in the presence of glutamine, human precision-cut renal cortical slices
      are metabolically viable and strongly respond to the ammoniagenic effect of
      valproate. Thus, this experimental model is suitable for metabolic and pharmaco
      toxicological studies.

PMID- 15579134
TI  - A novel site contributing to growth-arrest-specific gene 6 binding to its
      receptors as revealed by a human monoclonal antibody.
AB  - Gas6 (growth-arrest-specific gene 6) is a vitamin K-dependent protein known to
      activate the Axl family of receptor tyrosine kinases. It is an important
      regulator of thrombosis and many other biological functions. The C-terminus of
      Gas6 binds to receptors and consists of two laminin-like globular domains LG1 and
      LG2. It has been reported that a Ca2+-binding site at the junction of LG1 and LG2
      domains and a hydrophobic patch at the LG2 domain are important for receptor
      binding [Sasaki, Knyazev, Cheburkin, Gohring, Tisi, Ullrich, Timpl and Hohenester
      (2002) J. Biol. Chem. 277, 44164-44170]. In the present study, we developed a
      neutralizing human monoclonal antibody, named CNTO300, for Gas6. The antibody was
      generated by immunization of human IgG-expressing transgenic mice with
      recombinant human Gas6 protein and the anti-Gas6 IgG sequences were rescued from
      an unstable hybridoma clone. Binding of Gas6 to its receptors was partially
      inhibited by the CNTO300 antibody in a dose-dependent manner. To characterize
      further the interaction between Gas6 and this antibody, the binding kinetics of
      CNTO300 for recombinant Gas6 were compared with independently expressed LG1 and
      LG2. The CNTO300 antibody showed comparable binding affinity, yet different
      dependence on Ca2+, to Gas6 and LG1. No binding to LG2 was detected. In the
      presence of EDTA, binding of the antibody to Gas6 was disrupted, but no
      significant effect of EDTA on LG1 binding was evident. Further epitope mapping
      identified a Gas6 peptide sequence recognized by the CNTO300 antibody. This
      peptide sequence was found to be located at the LG1 domain distant from the Ca2+
      binding site and the hydrophobic patch. Co-interaction of Gas6 with its receptor
      and CNTO300 antibody was detected by BIAcore analysis, suggesting a second
      receptor-binding site on the LG1 domain. This hypothesis was further supported by
      direct binding of Gas6 receptors to an independently expressed LG1 domain. Our
      results revealed, for the first time, a second binding site for Gas6-receptor
      interaction.

PMID- 15579135
TI  - Role of compartmentalized redox-active iron in hydrogen peroxide-induced DNA
      damage and apoptosis.
AB  - Jurkat cells in culture were exposed to oxidative stress in the form of
      continuously generated hydrogen peroxide, obtained by the addition of glucose
      oxidase to the medium. This treatment induced a rapid, dose-dependent increase in
      the ICIP (intracellular calcein-chelatable iron pool). Early destabilization of
      lysosomal membranes and subsequent nuclear DNA strand breaks were also observed,
      as evaluated by the Acridine Orange relocation test and the comet assay
      respectively. Somewhat later, these effects were followed by a lowered
      mitochondrial membrane potential, with release of cytochrome c and apoptosis
      inducing factor. These events were all prevented if cells were pretreated with
      the potent iron chelator DFO (desferrioxamine) for a period of time (2-3 h) long
      enough to allow the drug to reach the lysosomal compartment following fluid-phase
      endocytosis. The hydrophilic calcein, a cleavage product of calcein acetoxymethyl
      ester following the action of cytosolic esterases, obviously does not penetrate
      intact lysosomal membranes, thus explaining why ICIP increased dramatically
      following lysosomal rupture. The rapid decrease in ICIP after addition of DFO to
      the medium suggests draining of cytosolic iron to the medium, rather than
      penetration of DFO through the plasma membrane. Most importantly, these
      observations directly connect oxidative stress and resultant DNA damage with
      lysosomal rupture and the release of redox-active iron into the cytosol and,
      apparently, the nucleus.

PMID- 15579136
TI  - Nitric oxide consumption through lipid peroxidation in brain cell suspensions and
      homogenates.
AB  - Mechanisms which inactivate NO (nitric oxide) are probably important in governing
      the physiological and pathological effects of this ubiquitous signalling
      molecule. Cells isolated from the cerebellum, a brain region rich in the NO
      signalling pathway, consume NO avidly. This property was preserved in brain
      homogenates and required both particulate and supernatant fractions. A purified
      fraction of the particulate component was rich in phospholipids, and NO
      consumption was inhibited by procedures that inhibited lipid peroxidation, namely
      a transition metal chelator, the vitamin E analogue Trolox and ascorbate oxidase.
      The requirement for the supernatant was accounted for by its content of ascorbate
      which catalyses metal-dependent lipid peroxidation. The NO-degrading activity of
      the homogenate was mimicked by a representative mixture of brain lipids together
      with ascorbate and, under these conditions, the lipids underwent peroxidation. In
      a suspension of cerebellar cells, there was a continuous low level of lipid
      peroxidation, and consumption of NO by the cells was decreased by approx. 50% by
      lipid-peroxidation inhibitors. Lipid peroxidation was also abolished when NO was
      supplied at a continuously low rate (approximately 100 nM/min), which explains
      why NO consumption by this process is saturable. Part of the activity remaining
      after the inhibition of lipid peroxidation was accounted for by contaminating red
      blood cells, but there was also another component whose activity was greatly
      enhanced when the cells were maintained under air-equilibrated conditions. A
      similar NO-consuming process was present in cerebellar glial cells grown in
      tissue culture but not in blood platelets or leucocytes, suggesting a specialized
      mechanism.

PMID- 15579137
TI  - Myelination triggers local loss of axonal CNR/protocadherin alpha family protein
      expression.
AB  - The cadherin-related neuronal receptor (CNR)/protocadherin (Pcdh) alpha family is
      one of the diverse protocadherin families expressed in developing axons. We
      observed a strong axonal expression of these proteins at late embryonic and early
      postnatal stages corresponding to regions where fibers had not yet been
      myelinated. We therefore followed the postnatal localization of CNR/Pcdh alpha
      protein in major axonal tracts, such as the internal capsule, lateral olfactory
      tract, and optic nerve, and found that its axonal localization was dramatically
      lost in parallel with the increased expression of myelin markers. Moreover, the
      hypomyelinated optic nerve tracts of the myelin-deficient Shiverer mouse
      exhibited elevated levels of CNR/Pcdh alpha expression. These axonal expression
      patterns of CNR/Pcdh alpha in wild-type and Shiverer mice were similar to those
      of growth associated protein 43 (GAP-43) and L1, both of which are associated
      with axonal maturation. Thus, myelination may be a trigger for the local loss of
      axonal CNR/Pcdh alpha protein, and this process may be important in the
      maturation of neural circuits.

PMID- 15579138
TI  - The role of NGF uptake in selective vulnerability to cell death in ageing
      sympathetic neurons.
AB  - We have examined the hypothesis that differences in nerve growth factor (NGF)
      uptake and transport determine vulnerability to age-related neurodegeneration.
      Neurons projecting to cerebral blood vessels (CV) in aged rats are more
      vulnerable to age-related degeneration than those projecting to the iris. Uptake
      of NGF was therefore examined in sympathetic neurons projecting from the superior
      cervical ganglion (SCG) to CV and iris in young and old rats by treating the
      peripheral processes of these neurons with different doses of I125-NGF. Total
      uptake of I125-NGF was reduced in old CV-projecting, but not iris-projecting,
      neurons. Numbers of radiolabelled neurons projecting to each target were counted
      in sectioned ganglia. The data showed age-related reductions in numbers of
      labelled neurons projecting to CV, but no change in numbers of neurons projecting
      to the iris. Calculation of uptake of I125-NGF per neuron unexpectedly showed no
      major age-related differences in either of the two neuron populations. However,
      uptake per neuron was considerably lower for young and old CV-projecting,
      compared to iris-projecting, SCG neurons. We hypothesized that variations in NGF
      uptake might affect neuronal survival in old age. Counts of SCG neurons using a
      physical disector following retrograde tracing with Fluorogold confirmed the
      selective vulnerability of CV-projecting neurons by showing a significant 37%
      loss of these neurons in the period between 15 and 24 months. In contrast, there
      was no significant loss of iris-projecting neurons. We conclude that
      vulnerability to, or protection from, age-related neurodegeneration and neuronal
      cell death are associated with life-long low, or high, levels of NGF uptake,
      respectively.

PMID- 15579139
TI  - Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of
      brain-derived neurotrophic factor in vivo: potential implication for neuronal
      cell death.
AB  - Neuronal loss has been observed in post mortem brains of patients with human
      immunodeficiency virus type 1 (HIV-1). Experimental evidence has implicated HIV-1
      derived envelope glycoprotein 120 (gp120) in the neuronal cell death observed in
      these patients. However, the intrinsic mechanisms by which gp120 causes
      neurotoxicity are still unknown. We have recently shown that the neurotoxic
      effect of gp120 in vitro is reduced by brain-derived neurotrophic factor (BDNF).
      We therefore tested the hypothesis that low levels of BDNF render neurons more
      sensitive to gp120. Gp120 was injected acutely into the striatum of BDNF
      heterozygous mice and wild-type littermates. BDNF heterozygous mice exhibited
      more apoptotic neurons in the striatum than wild-type mice, suggesting that BDNF
      is neuroprotective also in vivo. Because several neurodegenerative disorders are
      characterized by lack of trophic support, we tested the hypothesis that gp120 may
      cause apoptosis by reducing BDNF expression. Gp120 was injected acutely in the
      rat striatum and BDNF levels determined by a two-site immunoassay at various
      times after the injection. Gp120 elicited a dramatic decrease in BDNF protein
      levels by 24 h. Reduced BDNF levels were still present at 4 days. Cellular
      localization of BDNF immunoreactivity revealed that gp120 decreases BDNF
      immunoreactivity mainly in neuronal processes. This effect of gp120 precedes the
      peak of caspase-3 activation and neuronal cell death. We propose that one of the
      mechanisms whereby gp120 causes neurotoxicity is a reduction of the neurotrophic
      factor environment crucial for cell survival.

PMID- 15579140
TI  - Origin of acetylcholinesterase in the neuromuscular junction formed in the in
      vitro innervated human muscle.
AB  - Synaptic basal lamina is interposed between the pre- and postsynaptic membrane of
      the neuromuscular junction (NMJ). This position permits deposition of basal
      lamina-bound NMJ components of both neuronal and muscle fibre origin. One such
      molecule is acetylcholinesterase (AChE). The origin of NMJ AChE has been
      investigated previously as the answer would elucidate the relative contributions
      of muscle fibers and motor neurons to NMJ formation. However, in the experimental
      models used in prior investigations either the neuronal or muscular components of
      the NMJs were removed, or the NMJs were poorly differentiated. Therefore, the
      question of AChE origin in the intact and functional NMJ remains open. Here, we
      have approached this question using an in vitro model in which motor neurons,
      growing from embryonic rat spinal cord explants, form well differentiated NMJs
      with cultured human myotubes. By immunocytochemical staining with species
      specific anti-AChE antibodies, we are able to differentiate between human
      (muscular) and rat (neuronal) AChE at the NMJ. We observed strong signal at the
      NMJ after staining with human AChE antibodies, which suggests a significant
      muscular AChE contribution. However, a weaker, but still clearly recognizable
      signal is observed after staining with rat AChE antibodies, suggesting a smaller
      fraction of AChE was derived from motor neurons. This is the first report
      demonstrating that both motor neuron and myotube contribute synaptic AChE under
      conditions where they interact with each other in the formation of an intact and
      functional NMJ.

PMID- 15579141
TI  - Galectin-1 in regenerating motoneurons.
AB  - The exogenous application of recombinant galectin-1 has recently been shown to
      promote the rate of peripheral nerve regeneration. Endogenous neuronal galectin-1
      expression has recently been demonstrated to increase after axotomy. Here we
      demonstrate a significant increase in the endogenous neuronal expression of
      galectin-1 mRNA in facial motoneurons after either a nerve resection or crush
      injury in mice. This increase in galectin-1 expression was due in part to the
      loss of target-derived factor(s) as indicated by both the return of galectin-1
      expression to control levels following target re-innervation and the increase in
      galectin-1 expression after blockade of axonal transport by an interneuronal
      colchicine injection. Furthermore, interneuronal injections of glial-derived
      neurotrophic factor into the uninjured nerve also increased galectin-1 mRNA
      expression within facial motoneurons suggesting that positive signals may also be
      involved in the regulation of galectin-1 expression. Galectin-1 null mutant mice
      showed an attenuated rate of functional recovery of whisking movement after a
      facial nerve crush.

PMID- 15579142
TI  - Differential activation of MAPK in injured and uninjured DRG neurons following
      chronic constriction injury of the sciatic nerve in rats.
AB  - To investigate the intracellular signal transduction pathways involved in the
      pathophysiological mechanisms of neuropathic pain after partial nerve injury, we
      examined the activation of extracellular signal-regulated protein kinase (ERK)
      and p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglion (DRG)
      in the chronic constriction injury (CCI) model. The CCI induced an increase in
      the phosphorylation of ERK in predominantly injured medium-sized and large-sized
      DRG neurons and in satellite glial cells. Treatment with the MAPK kinase 1/2
      inhibitor, U0126, suppressed CCI-induced mechanical allodynia and partially
      reversed the increase in neuropeptide Y (NPY) expression in damaged DRG neurons.
      In contrast, the CCI induced the activation of p38, mainly in uninjured small-to
      medium-diameter DRG neurons and in satellite glial cells. The p38 inhibitor,
      SB203580, reversed the CCI-induced heat hyperalgesia and also the increase in
      brain-derived neurotrophic factor (BDNF) expression in intact DRG neurons. On the
      other hand, the nerve growth factor (NGF)-induced increase in BDNF expression in
      small-to-medium-diameter neurons was reversed by SB203580, whereas the anti-NGF
      induced increase in NPY in medium-sized and large-sized neurons was partially
      blocked by U0126. Taken together, our results demonstrate that the activation of
      ERK and p38 and also the changes in NPY and BDNF expression may occur in
      different populations of DRG neurons after CCI, partially through alterations in
      the target-derived NGF. These changes in injured and intact primary afferents are
      likely to have a substantial role in pathological states, and MAPK pathways in
      nociceptors may be potential targets for the development of novel analgesics.

PMID- 15579143
TI  - Caspase signalling in neuropathic and inflammatory pain in the rat.
AB  - Whereas small-fibre sensory neuropathies might ultimately lead to cell death and
      loss of sensation, they first progress through a phase, which might last for
      years, characterized by the presence of analgesia-resistant neuropathic
      dysesthesias and pain. Much previous research has addressed these two phases as
      separate phenomena mediated by presumably discrete biochemical mechanisms. We
      hypothesized that activity in signalling pathways that ultimately lead to
      apoptosis plays a critical role in the generation of neuropathic pain, before
      death of sensory neurons becomes apparent. We have tested the hypothesis that
      activator and effector caspases, defining components of programmed cell death
      (apoptosis) signalling pathways, also contribute to pain-related behaviour in
      animals with small-fibre peripheral neuropathies and that the death receptor
      ligand, tumour necrosis factor-alpha, and its downstream second messenger,
      ceramide, also produce pain-related behaviour via this mechanism. In two models
      of painful peripheral neuropathy, HIV/AIDS therapy (induced by the nucleoside
      reverse transcriptase inhibitor, dideoxycytidine), and cancer chemotherapy
      (induced by vincristine) peripheral neuropathy, and for pain-related behaviour
      induced by tumour necrosis factor-alpha and its second messenger, ceramide,
      inhibition of both activator (1, 2, 8 and 9) and effector (3) caspases attenuates
      neuropathic pain-related behaviour, although has no effect in streptozotocin
      diabetic neuropathy and control rats. We conclude that during a latent phase,
      before apoptotic cell death is manifest, the caspase signalling pathway can
      contribute to pain in small-fibre peripheral neuropathies, and that
      inflammatory/immune mediators also activate these pathways. This suggests that
      these pathways are potential targets for novel pharmacological agents for the
      treatment of inflammatory as well as neuropathic pain.

PMID- 15579144
TI  - Rt-PA causes a significant increase in endogenous u-PA during experimental focal
      cerebral ischemia.
AB  - The aim of this study was to investigate the effects of different doses of
      exogenous recombinant human tissue plasminogen activator (rt-PA) on the
      endogenous cerebral plasminogen-plasmin system in focal ischemia in rats.
      Ischemia was induced using the suture model. Each group of rats (n = 6) received
      either treatment (0.9, 9 or 18 mg rt-PA/kg body weight) or saline (control group)
      at the end of ischemia; a sham-operated group was added. The activity of the
      plasminogen activators was measured by casein-dependent plasminogen zymography.
      In the cortex urokinase (u-PA) rose from sham (no ischemia), 91 +/- 7% to
      ischemia, 176 +/- 10% (P < 0.005). Increasing rt-PA doses led to further
      significant (P < 0.001) cortical u-PA activation which was maximal at 18 mg: 249
      +/- 13%. An extreme increase in the u-PA activity was observed in the basal
      ganglia to 1019 +/- 22% (P < 0.001). This increase was further aggravated by
      higher rt-PA doses (18 mg, 1236 +/- 15%; P < 0.001). The t-PA level did not
      change I3R24 during (3 h ischemia followed by reperfusion for 24 h); however,
      during low and moderate doses of rt-PA, endogenous t-PA was reduced. In
      conclusion, while ischemia leads to a significant increase in u-PA, mainly in the
      basal ganglia, t-PA is not altered. Increasing doses of rt-PA lead to a further
      elevation of u-PA. Thus, u-PA seems to play a major role in the endogenous
      plasminogen activator system following focal cerebral ischemia.

PMID- 15579145
TI  - Fez1 is layer-specifically expressed in the adult mouse neocortex.
AB  - The mammalian cerebral neocortex occupies the largest area of the cerebral cortex
      and is cytoarchitectually composed of six layers (I-VI). Recent molecular
      analysis has begun to reveal the existence of various developmental programs,
      including the genetic regulation of arealization of the neocortex. Although an
      increasing number of molecular determinants of the developmental stages of the
      neocortex have been identified, no genes specifically expressed in the adult
      neocortex have been identified to date. By global screening using microarrays,
      combined with systematic in situ hybridization, we identified a zinc-finger type
      transcription factor, Fez1, which is expressed predominantly in the mouse adult
      neocortex. No other genes in the neocortex have been shown to date to have their
      expression with such high specificity. Using two-color in situ hybridization, we
      show that Fez1 is mainly expressed in cortical layers V and VI, not in gamma
      aminobutyric acid neurons but in pyramidal neurons, the projection neurons of the
      cerebral cortex. Immunohistochemistry also shows that Fez1 is expressed in deep
      layers of the neocortex. Fez1 will be invaluable not only for the molecular
      understanding of corticogenesis but also for understanding the physiological
      functions of the adult neocortex, as well as for the use of its promoter in gene
      manipulated animals and in conditional expression systems.

PMID- 15579146
TI  - Autoinhibition of transmitter release from PC12 cells and sympathetic neurons
      through a P2Y receptor-mediated inhibition of voltage-gated Ca2+ channels.
AB  - Although feedback inhibition of noradrenaline release by coreleased nucleotides
      is a well known phenomenon, it remained unclear which P2 receptor subtypes and
      associated signalling cascades may be involved. In the rat pheochromocytoma cell
      line PC12, 2-methylthio-ADP reduced noradrenaline release triggered by K+
      depolarization more potently than ADP and ATP, whereas UDP or UTP failed to do
      so. The inhibition by ADP was abolished by pertussis toxin and antagonized by
      reactive blue 2, 2-methylthio-AMP, and AR-C69931MX, but not by suramin. AR
      C69931MX acted as a competitive antagonist with an apparent affinity of 2 nm, but
      did not alter noradrenaline release, when PC12 cells were continuously
      superfused. However, when the superfusion was halted during K+ depolarization,
      release was significantly reduced and this inhibition was attenuated by AR
      C69931MX, thus revealing ongoing autoinhibition. Rises in cellular cyclic AMP did
      not alter depolarization-evoked release nor its reduction by ADP, even though the
      nucleotide did inhibit cyclic AMP accumulation. ADP and the direct Ca2+ channel
      blocker Cd2+ inhibited voltage-activated Ca2+ currents, but not ATP-induced
      currents, and both agents reduced K+-evoked, but not ATP-evoked, release. Hence,
      if voltage-gated Ca2+ channels do not contribute to stimulation-evoked release,
      ADP fails to exert its inhibitory action. In primary cultures of rat sympathetic
      neurons, ADP also reduced Ca2+ currents and K+-evoked noradrenaline release, and
      AR-C69931MX acted again as competitive antagonist with an apparent affinity of 3
      nm. These results show that P2Y12 receptors mediate an autoinhibition of
      transmitter release from PC12 cells and sympathetic neurons through an inhibition
      of voltage-gated Ca2+ channels.

PMID- 15579147
TI  - Signaling complex formation of phospholipase Cbeta4 with metabotropic glutamate
      receptor type 1alpha and 1,4,5-trisphosphate receptor at the perisynapse and
      endoplasmic reticulum in the mouse brain.
AB  - Upon activation of cell surface receptors coupled to the Gq subclass of G
      proteins, phospholipase C (PLC) beta hydrolyses membrane phospholipid to yield a
      pair of second messengers, inositol 1,4,5-trisphosphate (IP3) and 1,2
      diacylglycerol. PLCbeta4 has been characterized as the isoform enriched in
      cerebellar Purkinje cells (PCs) and the retina and involved in motor and visual
      functions. Here we examined cellular and subcellular distributions of PLCbeta4 in
      adult mouse brains. Immunohistochemistry showed that high levels of PLCbeta4 were
      detected in the somatodendritic domain of neuronal populations expressing the
      metabotropic glutamate receptor (mGluR) type 1alpha, including olfactory
      periglomerular cells, neurons in the bed nucleus anterior commissure, thalamus,
      substantia nigra, inferior olive, and unipolar brush cells and PCs in the
      cerebellum. Low to moderate levels were detected in many other mGluR1alpha
      positive neurons and in a few mGluR1alpha-negative neurons. In PCs, immunogold
      electron microscopy localized PLCbeta4 to the perisynapse, at which mGluR1alpha
      is concentrated, and to the smooth endoplasmic reticulum in dendrites and spines,
      an intracellular Ca2+ store gated by IP3 receptors. In the cerebellum, immunoblot
      demonstrated its concentrated distribution in the post-synaptic density and
      microsomal fractions, where mGluR1alpha and type 1 IP3 receptor were also greatly
      enriched. Furthermore, PLCbeta4 formed coimmunoprecipitable complexes with
      mGluR1alpha, type 1 IP3 receptor and Homer 1. These results suggest that PLCbeta4
      is preferentially localized in the perisynapse and smooth endoplasmic reticulum
      as a component of the physically linked phosphoinositide signaling complex. This
      close molecular relationship might provide PLCbeta4 with a high-fidelity effector
      function to mediate various neuronal responses under physiological and
      pathophysiological conditions.

PMID- 15579148
TI  - Pre- and postsynaptic GABA receptors at reciprocal dendrodendritic synapses in
      the olfactory bulb.
AB  - Presynaptic ionotropic receptors are important regulators of synaptic function;
      however, little is known about their organization in the presynaptic membrane. We
      show here a different spatial organization of presynaptic and postsynaptic
      GABA(A) receptors at reciprocal dendrodendritic synapses between mitral and
      granule cells in the rat olfactory bulb. Using postembedding electron microscopy,
      we have found that mitral cell dendrites express GABA(A) receptors at
      postsynaptic specializations of symmetric (GABAergic) synapses, as well as at
      presynaptic sites of asymmetric (glutamatergic) synapses. Analysis of the
      subsynaptic distribution of gold particles revealed that in symmetric synapses
      GABA(A) receptors are distributed along the entire postsynaptic membrane, whereas
      in asymmetric synapses they are concentrated at the edge of the presynaptic
      specialization. To assess the specificity of immunogold labelling, we analysed
      the olfactory bulbs of mutant mice lacking the alpha1 subunit of GABA(A)
      receptors. We found that in wild-type mice alpha1 subunit immunoreactivity was
      similar to that observed in rats, whereas in knockout mice the immunolabelling
      was abolished. These results indicate that in mitral cell dendrites GABA(A)
      receptors are distributed in a perisynaptic domain that surrounds the presynaptic
      specialization. Such presynaptic receptors may be activated by spillover of GABA
      from adjacent inhibitory synapses and modulate glutamate release, thereby
      providing a novel mechanism regulating dendrodendritic inhibition in the
      olfactory bulb.

PMID- 15579149
TI  - Impaired formation of the inner retina in an AChE knockout mouse results in
      degeneration of all photoreceptors.
AB  - Blinding diseases can be assigned predominantly to genetic defects of the
      photoreceptor/pigmented epithelium complex. As an alternative, we show here for
      an acetylcholinesterase (AChE) knockout mouse that photoreceptor degeneration
      follows an impaired development of the inner retina. During the first 15
      postnatal days of the AChE-/- retina, three major calretinin sublaminae of the
      inner plexiform layer (IPL) are disturbed. Thereby, processes of amacrine and
      ganglion cells diffusely criss-cross throughout the IPL. In contrast, parvalbumin
      cells present a nonlaminar IPL pattern in the wild-type, but in the AChE-/- mouse
      their processes become structured within two 'novel' sublaminae. During this
      early period, photoreceptors become arranged regularly and at a normal rate in
      the AChE-/- retina. However, during the following 75 days, first their outer
      segments, and then the entire photoreceptor layer completely degenerate by
      apoptosis. Eventually, cells of the inner retina also undergo apoptosis. As
      butyrylcholinesterase (BChE) is present at a normal level in the AChE-/- mouse,
      the observed effects must be solely due to the missing AChE. These are the first
      in vivo findings to show a decisive role for AChE in the formation of the inner
      retinal network, which, when absent, ultimately results in photoreceptor
      degeneration.

PMID- 15579150
TI  - Nitric oxide modulates the transfer function between cones and horizontal cells
      during changing conditions of ambient illumination.
AB  - It has been suggested that nitric oxide (NO) serves as a retinal neuromodulator,
      adjusting retinal function to changing conditions of adaptation. We tested this
      hypothesis in the intact turtle retina by recording the photoresponses of L-cones
      and L1-horizontal cells, while changing retinal NO level and background
      illumination. Raising the retinal level of NO, by adding an NO donor (sodium
      nitroprusside) or the precursor for NO synthesis (L-arginine), induced response
      augmentation in L-cones and L1-horizontal cells. Lowering retinal level of NO by
      adding L-NAME, an inhibitor of NO synthesis, reduced the amplitudes of the
      photoresponses in these retinal neurons. The transfer function between L-cones
      and L1-horizontal cells, constructed from the photoresponses of these cells, was
      modified by NO and by background lights. The nonlinear transfer function,
      characteristic of the dark-adapted retina, became linear and of low gain when the
      retinal NO level was increased or by increasing the level of ambient
      illumination. In contrast, inhibiting NO synthesis in the light-adapted retina
      induced nonlinearity in the cone-to-horizontal cell transfer function similar to
      that seen in the dark-adapted state. NADPH diaphorase histochemistry, conducted
      on isolated retinal cells, demonstrated activity in cone inner segments and
      distal process of Muller cells. These findings support the hypothesis that NO
      synthesis in the distal turtle retina is triggered by background illumination,
      and that NO acts to adjust the modes of visual information processing in the
      outer plexiform layer to the conditions required during continuous background
      illumination.

PMID- 15579151
TI  - Cilium-attached and excised patch-clamp recordings of odourant-activated Ca
      dependent K channels from chemosensory cilia of olfactory receptor neurons.
AB  - It has previously been proposed that a Ca2+-dependent K+ conductance is
      implicated in the inhibitory odourant response in rat and toad olfactory receptor
      neurons. Previous whole-cell and single-channel measurements on inside-out
      excised patches, in addition to immunochemical evidence, indicated the presence
      of Ca2+-dependent K+ channels in olfactory cilia, the transducing structures of
      these sensory cells. Ca2+-dependent K+ channels opened in 'on-cilium' membrane
      patches from C. caudiverbera upon odourant stimulation. Furthermore, after
      excision in the inside-out configuration, the channel could be opened by
      micromolar Ca2+, in a Ca2+-dependent fashion, but it was unresponsive to cyclic
      AMP. We estimated that the Ca2+ concentration in the proximity of a Ca2+
      dependent K+ channel within the cilia reaches at least 100 microM during the
      odour response. The K+ channel displayed a higher selectivity for K+ than for
      Na+. Our results support a role for this Ca2+-dependent K+ channel in
      chemotransduction.

PMID- 15579152
TI  - Transient Ca2+-permeable AMPA receptors in postnatal rat primary auditory
      neurons.
AB  - Fast excitatory transmission in the nervous system is mostly mediated by alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors whose
      subunit composition governs physiological characteristics such as ligand affinity
      and ion conductance properties. Here, we report that AMPA receptors at inner hair
      cell (IHC) synapses lack the GluR2 subunit and are transiently Ca2+-permeable
      before hearing onset as evidenced using agonist-induced Co2+ accumulation,
      Western blots and GluR2 confocal microscopy in the rat cochlea. AMPA (100 microM)
      induced Co2+ accumulation in primary auditory neurons until postnatal day (PND)
      10. This accumulation was concentration-dependent, strengthened by cyclothiazide
      (50 microM) and blocked by GYKI 52466 (80 microM) and Joro spider toxin (1
      microM). It was unaffected by D-AP5 (50 microM), and it could not be elicited by
      56 mM K+ or 1 mM NMDA + 10 microM glycine. Western blots showed that GluR1
      immunoreactivity, present in homogenates of immature cochleas, had disappeared by
      PND12. GluR2 immunoreactivity was not detected until PND10 and GluR3 and GluR4
      immunoreactivities were detected at all the ages examined. Confocal microscopy
      confirmed that the GluR2 immunofluorescence was not located postsynaptically to
      IHCs before PND10. In conclusion, AMPA receptors on maturing primary auditory
      neurons differ from those on adult neurons. They are probably composed of GluR1,
      GluR3 and GluR4 subunits and have a high Ca2+ permeability. The postsynaptic
      expression of GluR2 subunits may be continuously regulated by the presynaptic
      activity allowing for variations in the Ca2+ permeability and physiological
      properties of the receptor.

PMID- 15579153
TI  - Possible role of phosphatidylinositol 4,5 bisphosphate in luteinizing hormone
      releasing hormone-mediated M-current inhibition in bullfrog sympathetic neurons.
AB  - Luteinizing hormone releasing hormone (LHRH) is a physiological modulator of
      neuronal excitability in bullfrog sympathetic ganglia (BFSG). Actions of LHRH
      involve suppression of the noninactivating, voltage-dependent M-type K+ channel
      conductance (gM). We found, using whole-cell recordings from these neurons, that
      LHRH-induced suppression of gM was attenuated by the phospholipase C (PLC)
      inhibitor U73122 (10 microM) but not by the inactive isomer U73343 (10 microM).
      Buffering internal Ca2+ to 117 nM with intracellular 20 mM BAPTA + 8 mM Ca2+ or
      to < 10 nM with intracellular 20 mM BAPTA + 0.4 mM Ca2+ did not attenuate LHRH
      induced gM suppression. Suppression of gM by LHRH was not antagonized by the
      inositol 1,4,5 trisphosphate (InsP3) receptor antagonist heparin (approximately
      300 microM). Preventing phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis by
      blocking phosphatidylinositol-4-kinase with wortmannin (10 microM) or with the
      nonhydrolysable ATP analogue AMP-PNP (3 mM) prolonged recovery of LHRH-induced gM
      suppression. This effect was not produced by blocking phosphatidyl inositol-3
      kinase with LY294002 (10 microM). Rundown of gM was attenuated when cells were
      dialysed with 240 microM di-octanoyl PIP2 or 240 microM di-octanoyl
      phosphatidylinositol-3,4,5-trisphosphate (PIP3) but not with 240 microM di
      octanoyl phosphatidylcholine. LHRH-induced gM suppression was competitively
      antagonized by dialysis with 240 microM di-octanoyl PIP2, but not with di
      octanoyl phosphatidylcholine. These results would be expected if LHRH-induced gM
      suppression reflects a PLC-mediated decrease in plasma membrane PIP2 levels.

PMID- 15579154
TI  - Feedback control of Purkinje cell activity by the cerebello-olivary pathway.
AB  - The pathway from the deep cerebellar nuclei to the inferior olive, the source of
      the climbing fibre input to the cerebellum, inhibits olivary transmission. As
      climbing fibre activity can depress the background firing of the Purkinje cells,
      it was suggested that nucleo-olivary (N-O) inhibition is a negative feedback
      mechanism for regulating Purkinje cell excitability. This suggestion was
      investigated, in a set-up with decerebrate ferrets, both by blocking and by
      stimulating cerebellar output while recording Purkinje cell activity. Blocking
      the N-O pathway was followed by an increased climbing fibre activity and a
      dramatic reduction in simple spike firing. Stimulation of the N-O fibres
      depressed climbing fibre responses and caused an increase in simple spike firing.
      These results are taken as support for the feedback hypothesis.

PMID- 15579155
TI  - Transiently higher release probability during critical period at thalamocortical
      synapses in the mouse barrel cortex: relevance to differential short-term
      plasticity of AMPA and NMDA EPSCs and possible involvement of silent synapses.
AB  - Thalamocortical connections undergo remarkable plasticity during the critical
      period and mounting evidence serves to demonstrate that the activation of silent
      synapses at postsynaptic sites is an important underlying mechanism in this
      process. However, relatively little is known about the nature of the presynaptic
      properties. In the present study, we examined the release probability (Pr) of
      thalamocortical synaptic terminals on a layer IV neuron in the developing mouse
      barrel cortex. Using the conventional paired-pulse ratio (PPR) method, both AMPA
      and NMDA receptor-mediated PPR were observed during development. We found that
      the NMDA PPR increased gradually (thus, a reduction in Pr) from postnatal day
      (P)4 to P22 but, unexpectedly, the AMPA PPR exhibited a simultaneous decrease. We
      then used an additional method for assessing release probability, the observation
      of a progressive block of NMDA receptor-mediated EPSCs using MK-801. With this
      method, we were able to identify two classes of terminals with high or low
      probabilities of release. Interestingly, the higher release showed a reduction in
      probability during the critical period, consistent with the NMDA PPR results. We
      confirmed that the discrepancy between the NMDA and the AMPA PPR results was due
      to the existence of silent, or NMDA-only, synapses, as suggested in previous
      literature. By analysing the correlation between the NMDA or AMPA PPR and the PPR
      discrepancy, we discuss the hypothesis that the terminals with transiently higher
      probability of release were found preferentially on silent synapses. Our results
      suggest that these presynaptic sites may also have an active role in plasticity
      by working concomitantly with postsynaptic sites during the critical period.

PMID- 15579156
TI  - Synergistic action of GABA-A and NMDA receptors in the induction of long-term
      depression in glutamatergic synapses in the newborn rat hippocampus.
AB  - We show that activation of GABA(A) receptors (GABA(A)Rs) promotes induction of N
      methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD)
      of glutamatergic synapses in the newborn rat hippocampal area CA1 in a
      developmentally restricted manner. In the newborn rat hippocampus two
      mechanistically different types of LTD of glutamatergic synapses could be induced
      under similar experimental conditions. The form of the LTD induced depended on
      the stimulation protocol and on the age of the animal. Low-frequency stimulation
      (1 Hz) with 100 stimuli induced a robust homosynaptic, reversible LTD at
      postnatal days 2-8 (P2-P8) but not at P14. This LTD was blocked by the NMDAR
      antagonist AP5 or by the GABA(A)R antagonist picrotoxin. Use of a low-chloride
      solution in the patch pipette resulting in E(GABA-A) < -70 mV blocked the NMDAR
      dependent LTD, whereas clamping the cell to -40 mV during induction rescued it.
      In addition, it was possible to induce LTD at P14 with 100 stimuli if the cells
      were clamped to -40 mV during induction. Low-frequency stimulation with 900
      stimuli induced a robust homosynaptic, reversible LTD both at P2-P8 and at P14.
      However, neither AP5 nor picrotoxin affected the LTD induced by 900 pulses at P2
      P8. Instead, the 900 stimuli-induced LTD was blocked by the metabotropic
      glutamate receptor antagonists when co-applied with AP5. We suggest that during
      the first postnatal week postsynaptic depolarization provided by the activation
      of GABA(A)Rs shifts the threshold for the LTD induction, making the synapses more
      prone to activity-induced plasticity. From the second postnatal week onwards,
      when the GABA(A) responses are already hyperpolarizing, different mechanisms for
      LTD induction prevail.

PMID- 15579157
TI  - Effects of ventral hippocampal lesion on thermal and mechanical nociception in
      neonates and adult rats.
AB  - The proper maturation of the hippocampus is essential for the development of
      different behaviours, including memory, pain responses and avoidance. The
      mechanisms involved in the neurodevelopment of nociception have also been
      implicated in several neuropsychiatric disorders. The neonatal lesion of the
      ventral hippocampus (VH) in rats, an animal model of schizophrenia, can be
      utilized to study the developmental neurobiology of animal behaviour. We examined
      the nociceptive responses in this animal model at different stages of
      development. Rat pups were lesioned at postnatal day 7 by injecting ibotenic acid
      into the VH bilaterally, and then tested for thermal and mechanical nociception
      at the age of 35, 65 and 180 days. The nociceptive tests used were the hot plate
      (HP), paw pressure (PP) and tail flick (TF) tests. Another group of adult rats
      had the same lesion in the VH and then underwent the same tests at 28, 56 and 168
      days post-lesions. When compared with sham controls, the rats with neonatal VH
      lesion showed decreased latency for the HP and PP tests only after puberty. The
      TF test showed significant increase in latency for both groups at age 65 and 180
      days. The adult rats with VH lesion showed no major changes over all periods of
      testing. These results suggest that early lesion of VH can alter the development
      of the neural mechanisms involved in the processing of thermal and mechanical
      nociception.

PMID- 15579158
TI  - Pro-VGF-derived peptides induce penile erection in male rats: possible
      involvement of oxytocin.
AB  - The effect of five peptides derived from the C-terminal portion of rat pro-VGF
      (VGF(577-617), VGF(588-617), VGF(599-617), VGF(556-576) and VGF(588-597)) on
      penile erection was studied after injection into the hypothalamic paraventricular
      nucleus of male rats. VGF(577-617), VGF(588-617), VGF(599-617) and, to a lower
      extent, VGF(588-597) (0.1-2 microg) induced penile erection episodes in a dose
      dependent manner when injected into the paraventricular nucleus, while VGF(556
      576) was ineffective. VGF(588-617)-induced penile erection was reduced by
      nitro(omega)-L-arginine methylester (L-NAME; 20 microg), by morphine (5 microg)
      and by muscimol (1 microg), but not by dizocilpine [(+)MK-801; 1 microg], nor by
      cis-flupenthixol (10 microg) given into the paraventricular nucleus 10 min before
      the VGF peptide. d(CH2)5Tyr(Me)-Orn8-vasotocin (1 microg) effectively reduced
      VGF(588-617)-induced penile erection when given into the lateral ventricles but
      not when injected into the paraventricular nucleus. Immunocytochemistry with
      antibodies specific for the C-terminal nonapeptide sequence of pro-VGF (VGF(609
      617)) revealed numerous neuronal fibres and terminals within the paraventricular
      nucleus, including its parvocellular components. Here, many immunostained
      neuronal terminals impinged on parvocellular oxytocinergic neurons. The present
      results show for the first time that certain pro-VGF C-terminus-derived peptides
      promote penile erection when injected into the paraventricular nucleus and
      suggest that, within this nucleus, these or closely related pro-VGF-derived
      peptides may be released to influence sexual function by activating
      paraventricular oxytocinergic neurons mediating penile erection.

PMID- 15579159
TI  - Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats.
AB  - To determine whether the basal forebrain-hippocampal cholinergic system supports
      sexually dimorphic functionality, male and female Long-Evans rats were given
      either selective medial septum/vertical limb of the diagonal band (MS/VDB)
      cholinergic lesions using the neurotoxin 192 IgG-saporin or a control surgery and
      then postoperatively tested in a set of standard spatial learning tasks in the
      Morris water maze. Lesions were highly specific and effective as confirmed by
      both choline acetyltransferase/parvalbumin immunostaining and
      acetylcholinesterase histochemistry. Female controls performed worse than male
      controls in place learning and MS/VDB lesions failed to impair spatial learning
      in male rats, both consistent with previous findings. In female rats, MS/VDB
      cholinergic lesions facilitated spatial reference learning. A subsequent test of
      learning strategy in the water maze revealed a female bias for a response,
      relative to a spatial, strategy; MS/VDB cholinergic lesions enhanced the use of a
      spatial strategy in both sexes, but only significantly so in males. Together,
      these results indicate a sexually dimorphic function associated with MS/VDB
      hippocampal cholinergic inputs. In female rats, these neurons appear to support
      sex-specific spatial learning processes.

PMID- 15579160
TI  - Reduced food anticipatory activity in genetically orexin (hypocretin) neuron
      ablated mice.
AB  - Daily restricted feeding (RF) produces an anticipatory locomotor activity rhythm
      and entrains the peripheral molecular oscillator independently of the central
      pacemaker located in the suprachiasmatic nucleus (SCN). As orexins (hypocretins)
      are neuropeptides that coordinate sleep/wake patterns and motivated behaviours,
      such as food seeking, we studied the involvement of orexin in the food
      anticipatory activity (FAA) induced by RF. Daily RF shifted the mRNA rhythm of a
      clock-controlled gene mDbp in the cerebral cortex and caudate putamen but not in
      the SCN. Under these experimental conditions, prepro-orexin mRNA and orexin A
      immunoreactivity in the lateral hypothalamic area (LHA) did not show daily
      variation. Fasting increased the number of orexin A-ir cells, while RF did not.
      However, RF shifted the peak of Fos expression of the orexin neurons from night
      to day. Genetic ablation of orexin neurons in orexin/ataxin-3 transgenic mice
      severely reduced the formation of FAA under RF conditions. The expression of
      mNpas2 mRNA, a transcription factor thought to be involved in regulation of the
      food entrainable oscillator as well as mPer1 and mBmal1 mRNA, was reduced in the
      forebrain of orexin/ataxin-3 mice. Based on these results, we suggest that
      activity of the orexin neuron in the LHA contributes to the promotion and
      maintenance of FAA.

PMID- 15579161
TI  - Autonomous activity of CaMKII is only transiently increased following the
      induction of long-term potentiation in the rat hippocampus.
AB  - A major role has been postulated for a maintained increase in the autonomous
      activity of CaMKII in the expression of long-term potentiation (LTP). However,
      attempts to inhibit the expression of LTP with CaMKII inhibitors have yielded
      inconsistent results. Here we compare the changes in CaMKII autonomous activity
      and phosphorylation at Thr286 of alphaCaMKII in rat hippocampal slices using
      chemical or tetanic stimulation to produce either LTP or short-term potentiation
      (STP). Tetanus-induced LTP in area CA1 requires CaMKII activation and Thr286
      phosphorylation of alphaCaMKII, but we did not observe an increase in autonomous
      activity. Next we induced LTP by 10 min exposure to 25 mM tetraethyl-ammonium
      (TEA) or 5 min exposure to 41 mM potassium (K) after pretreatment with calyculin
      A. Exposure to K alone produced STP. These protocols allowed us to monitor
      temporal changes in autonomous activity during and after exposure to the
      potentiating chemical stimulus. In chemically induced LTP, autonomous activity
      was maximally increased within 30 s whereas this increase was significantly
      delayed in STP. However, in both LTP and STP the two-fold increase in autonomous
      activity measured immediately after stimulation was short-lived, returning to
      baseline within 2-5 min after re-exposure to normal ACSF. In LTP, but not in STP,
      the phosphorylation of alphaCaMKII at Thr286 persisted for at least 60 min after
      stimulation. These results confirm that LTP is associated with a maintained
      increase in autophosphorylation at Thr286 but indicate that a persistent increase
      in the autonomous activity of CaMKII is not required for the expression of LTP.

PMID- 15579162
TI  - 5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release,
      locomotor response and behavioural sensitization to opiates and psychostimulants.
AB  - Addictive properties of drugs of misuse are generally considered to be mediated
      by an increased release of dopamine (DA) in the ventral striatum. However, recent
      experiments indicated an implication of alpha1b-adrenergic receptors in
      behavioural responses to psychostimulants and opiates. We show now that DA
      release induced in the ventral striatum by morphine (20 mg/kg) is completely
      blocked by prazosin (1 mg/kg), an alpha1-adrenergic antagonist. However, morphine
      induced increases in DA release in the ventral striatum were found to be similar
      in mice deleted for the alpha1b-adrenergic receptor (alpha1b-AR KO) and in wild
      type (WT) mice, suggesting the presence of a compensatory mechanism. This acute
      morphine-evoked DA release was completely blocked in alpha1b-AR KO mice by
      SR46349B (1 mg/kg), a 5-HT2A antagonist. SR46349B also completely blocked, in
      alpha1b-AR KO mice, the locomotor response and the development of behavioural
      sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg). Accordingly,
      the concomitant blockade of 5-HT2A and alpha1b-adrenergic receptors in WT mice
      entirely blocked acute locomotor responses but also the development of
      behavioural sensitization to morphine, D-amphetamine or cocaine (10 mg/kg). We
      observed, nevertheless, that inhibitory effects of each antagonist on locomotor
      responses to morphine or D-amphetamine were more than additive (160%) in naive WT
      mice but not in those sensitized to either drug. Because of these latter data and
      the possible compensation by 5-HT2A receptors for the genetic deletion of alpha1b
      adrenergic receptors, we postulate the existence of a functional link between
      these receptors, which vanishes during the development of behavioural
      sensitization.

PMID- 15579163
TI  - Stressor-related impairment of synaptic transmission in hippocampal slices from
      alpha-synuclein knockout mice.
AB  - The role of alpha-synuclein (alpha-Syn) has recently received considerable
      attention because it seems to play a role in Parkinson's disease (PD). Missense
      mutations in the alpha-Syn gene were found in autosomal dominant PD and alpha-Syn
      was shown to be a major constituent of protein aggregates in sporadic PD and
      other synucleinopathies. Under normal conditions, alpha-Syn protein is found
      exclusively in synaptic terminals. However, the potential participation of alpha
      synuclein in maintaining and regulating synaptic efficacy is unknown. We have
      investigated the excitatory synaptic modulation of alpha-synuclein in CA1
      pyramidal neurons, using the in vitro hippocampal slice technique. The 4
      aminopyridine-induced increase of both spontaneous excitatory postsynaptic
      current (EPSC) frequency and amplitude was significantly higher in alpha-Syn wild
      type than knockout mice, whereas basal spontaneous EPSC frequency and amplitude
      was similar in both animals. As the spontaneous synaptic activity was abolished
      by tetrodotoxin, which indicates that it was a result of action potential
      mediated transmitter release from presynaptic terminals, spontaneous EPSC changes
      observed in alpha-Syn knockout mice suggest that these animals present a
      modification of synaptic transmission with a presynaptic origin. Presynaptic
      depression of evoked EPSCs by hypoxia or adenosine was significantly larger in
      alpha-Syn knockout than in wild-type mice, further supporting the hypothesis of
      regulation of synaptic transmission by alpha-Syn. Together, these observations
      indicate that the loss of alpha-Syn reduces synaptic efficacy when the
      probability of transmitter release is modified. We conclude that alpha-Syn might
      have important actions on the maintenance of the functional integrity of synaptic
      transmission and its regulation in hippocampus.

PMID- 15579164
TI  - Progressive abnormalities in skeletal muscle and neuromuscular junctions of
      transgenic mice expressing the Huntington's disease mutation.
AB  - Huntington's disease (HD) is a neurodegenerative disorder with complex symptoms
      dominated by progressive motor dysfunction. Skeletal muscle atrophy is common in
      HD patients. Because the HD mutation is expressed in skeletal muscle as well as
      brain, we wondered whether the muscle changes arise from primary pathology. We
      used R6/2 transgenic mice for our studies. Unlike denervation atrophy, skeletal
      muscle atrophy in R6/2 mice occurs uniformly. Paradoxically however, skeletal
      muscles show age-dependent denervation-like abnormalities, including
      supersensitivity to acetylcholine, decreased sensitivity to mu-conotoxin, and
      anode-break action potentials. Morphological abnormalities of neuromuscular
      junctions are also present, particularly in older R6/2 mice. Severely affected
      R6/2 mice show a progressive increase in the number of motor endplates that fail
      to respond to nerve stimulation. Surprisingly, there was no constitutive
      sprouting of motor neurons in R6/2 muscles, even in severely atrophic muscles
      that showed other denervation-like characteristics. In fact, there was an age
      dependent loss of regenerative capacity of motor neurons in R6/2 mice. Because
      muscle fibers appear to be released from the activity-dependent cues that
      regulate membrane properties and muscle size, and motor axons and nerve terminals
      become impaired in their capacity to release neurotransmitter and to respond to
      stimuli that normally evoke sprouting and adaptive reinnervation, we speculate
      that in these mice there is a progressive dissociation of trophic signalling
      between motor neurons and skeletal muscle. However, irrespective of the cause,
      the abnormalities at neuromuscular junctions we report here are likely to
      contribute to the pathological phenotype in R6/2 mice, particularly in late
      stages of the disease.

PMID- 15579165
TI  - Extensive exercise is not harmful in amyotrophic lateral sclerosis.
AB  - Whether physical activity increases risk or promotes progression of motor neurone
      degeneration in amyotrophic lateral sclerosis (ALS) is still debated. Current
      pathophysiological hypotheses include excitotoxicity, oxidative stress and
      increased calcium loads as causes of selective degeneration of vulnerable motor
      neurones. Vigorous exercise might amplify these factors by increasing firing
      rates at motor neurones. To test this hypothesis, we constrained a transgenic
      mouse model of ALS overexpressing the mutant human form of the Cu/Zn superoxide
      dismutase-1 (SOD-1) to a lifetime exercise on motor-driven running wheels for 10
      h daily (active group, n = 12). Onset and progression of disease were assessed by
      grip strength, stride length and tight rope test. Data were compared with SOD-1
      mice placed in running wheels set to slow speed (sedentary group, n = 13).
      Untreated SOD-1 mice were an additional control group (n = 12). We found no
      differences in disease onset, which was determined by a change-point analysis
      using an iterative fitting of segmented linear regression models, or in disease
      progression. However, the running group showed a non-significant 6-day
      improvement in survival (133.7 +/- 3.2 days) compared with the sedentary group
      (127.2 +/- 3.2 days) and a 4-day improvement compared with the control group
      (129.1 +/- 2.5 days). We demonstrate that a lifetime of vigorous exercise does
      not promote onset or progression of motor degeneration in SOD-1-mediated ALS.
      Moreover, the results suggest that the level of excitatory input and calcium
      turnover at motor neurones, both of which should be increased by running
      activity, do not interfere with the pathophysiology of SOD-1-mediated ALS.

PMID- 15579166
TI  - Dissociation between short-term increased graft survival and long-term functional
      improvements in Parkinsonian rats overexpressing glial cell line-derived
      neurotrophic factor.
AB  - The present study was designed to analyse whether continuous overexpression of
      glial cell line-derived neurotrophic factor (GDNF) in the striatum by a
      recombinant lentiviral vector can provide improved cell survival and additional
      long-term functional benefits after transplantation of fetal ventral
      mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6
      hydroxydopamine lesion resulted in an 80-90% depletion of nigral dopamine cells
      and striatal fiber innervation, leading to stable motor impairments. Histological
      analysis performed at 4 weeks after grafting into the GDNF-overexpressing
      striatum revealed a twofold increase in the number of surviving tyrosine
      hydroxylase (TH)-positive cells, as compared with grafts placed in control (green
      fluorescent protein-overexpressing) animals. However, in animals that were
      allowed to survive for 6 months, the numbers of surviving TH-positive cells in
      the grafts were equal in both groups, suggesting that the cells initially
      protected at 4 weeks failed to survive despite the continued presence of GDNF.
      Although cell survival was similar in both grafted groups, the TH-positive fiber
      innervation density was lower in the GDNF-treated grafted animals (30% of normal)
      compared with animals with control grafts (55% of normal). The vesicular
      monoamine transporter-2-positive fiber density in the striatum, by contrast, was
      equal in both groups, suggesting that long-term GDNF overexpression induced a
      selective down-regulation of TH in the grafted dopamine neurons. Behavioral
      analysis in the long-term grafted animals showed that the control grafted animals
      improved their performance in spontaneous motor behaviors to approximately 50% of
      normal, whereas the GDNF treatment did not provide any additional recovery.

PMID- 15579167
TI  - Long-term sensorineural hearing loss induces functional changes in the rat
      auditory nerve.
AB  - Loss of cochlear hair cells in the rat initiates degenerative change within the
      primary auditory neurons (ANs) of the cochlea. These degenerative changes include
      loss of peripheral processes, demyelination and ultimately cell death. This
      pathology will affect the biophysical processes involved in action potential
      generation and propagation to an electrical stimulus via a cochlear implant. We
      measured the response properties of ANs, with particular reference to their
      refractory behaviour, in normal, short- (9 weeks) and long-term (> 52 weeks)
      deafened rats. AN loss was moderate in the short-term and severe in the long-term
      deafened animals. AN activity was elicited using a brief electrical stimulus
      delivered via a bipolar electrode array implanted into the cochlea. The general
      response properties of ANs recorded from deafened cochleae were similar to those
      observed in normal cochleae, i.e. a monotonic increase in the probability of
      firing and a decrease in response latency and temporal jitter with increasing
      stimulus intensity. However, the absolute refractory period was significantly
      prolonged in animals deaf for > 12 months (P = 0.0026). Deafened animals also
      exhibited a highly significant increase in threshold compared with normal
      controls (P < 0.001). These functional changes have implications for recipients
      of cochlear implants and potential therapies directed toward halting or reversing
      AN pathology.

PMID- 15579168
TI  - Recovery and refractoriness of auditory evoked fields after gaps in click trains.
AB  - When clicks are presented in a train at a rate above approximately 5 Hz, they
      evoke a sustained field in human auditory cortex that can be recorded by
      magnetoencephalography. In this study we evaluated how this sustained field
      continues when a click train is interrupted by a silent gap. The stimuli were
      click trains with interclick intervals of either 12 or 24 ms, which produce
      pitches of 83.3 or 41.7 Hz, respectively. The click trains were 996 ms in
      duration with a gap of 12, 24, 48, 96, or 192 ms beginning 504 ms post-stimulus
      onset. The sustained field for click trains with short gaps was similar to the
      one evoked by a continuous click train. Subtraction of the response evoked by a
      solitary click train of 504 ms enabled estimation of the sustained field in the
      interval after the gap. The comparison revealed that the sustained field
      amplitude after the gap was larger than that at the onset of the initial click
      train in the interval from 150 to 350 ms after onset, and the difference
      decreased with gap duration. In contrast, the transient P1m was refractory for
      gaps up to 48 ms, but had nearly recovered its initial amplitude for gaps of 192
      ms. We discuss how these results might relate to the perception, i.e. if an
      interrupted click train is perceived as one continuous sound with a transient gap
      or as two successive events.

PMID- 15579169
TI  - Is there a role of visual cortex in spatial hearing?
AB  - The integration of auditory and visual spatial information is an important
      prerequisite for accurate orientation in the environment. However, while visual
      spatial information is based on retinal coordinates, the auditory system receives
      information on sound location in relation to the head. Thus, any deviation of the
      eyes from a central position results in a divergence between the retinal visual
      and the head-centred auditory coordinates. It has been suggested that this
      divergence is compensated for by a neural coordinate transformation, using a
      signal of eye-in-head position. Using functional magnetic resonance imaging, we
      investigated which cortical areas of the human brain participate in such auditory
      visual coordinate transformations. Sounds were produced with different interaural
      level differences, leading to left, right or central intracranial percepts, while
      subjects directed their gaze to visual targets presented to the left, to the
      right or straight ahead. When gaze was to the left or right, we found the primary
      visual cortex (V1/V2) activated in both hemispheres. The occipital activation did
      not occur with sound lateralization per se, but was found exclusively in
      combination with eccentric eye positions. This result suggests a relation of
      neural processing in the visual cortex and the transformation of auditory spatial
      coordinates responsible for maintaining the perceptual alignment of audition and
      vision with changes in gaze direction.

PMID- 15579170
TI  - Entorhinal cortex contributes to object-in-place scene memory.
AB  - Four rhesus monkeys (Macaca mulatta) were trained preoperatively in a test of
      object-in-place scene memory. They were presented daily with lists of unique
      computer-generated scenes each containing a spatial array of multiple individual
      objects. Within each scene, objects to be discriminated appeared in the
      foreground, each occupying a unique location, and monkeys were required to
      correctly discriminate the rewarded object to receive a food reward. Once this
      preoperative criterion was attained, the monkeys received bilateral entorhinal
      cortex ablation performed as either one or two surgical operations with a period
      of testing following each. Postoperatively, they were significantly impaired in
      learning new object-in-place scene problems. These results show that the
      entorhinal cortex, like anatomically related structures including the perirhinal
      cortex and the fornix, contributes to object-in-place scene learning.

PMID- 15579171
TI  - Cortico-basal ganglia pathways are essential for the recall of well-established
      visuomotor associations.
AB  - Recent human neuroimaging studies, supported by lesion studies with nonhuman
      primates, have suggested that learning arbitrary associations between sensory
      cues and behavioural responses requires interactions between the infero-temporal,
      prefrontal and premotor cortices. We directly tested the hypothesis suggested
      from our neuroimaging experiments that functional links between the basal ganglia
      and premotor cortex are involved in the process via which task performance
      becomes automatic. We made unilateral excitotoxic lesions, centred on the
      internal pallidum, in four macaques previously given extensive experience on the
      associations between nonspatial visual cues and movements of a joystick. The
      basal ganglia lesion was later combined with a premotor cortical lesion in the
      opposite hemisphere so as to interrupt the connections between them. Three of the
      animals were subsequently found to be impaired in relearning pre-operatively
      acquired associations; they eventually succeeded but made three-times as many
      errors. A fourth animal was unimpaired but its premotor cortex lesion was later
      found to be incomplete. Response times were only marginally increased and the
      learning of novel associations appeared relatively unaffected by these lesions.
      As a control, the effects of a unilateral premotor cortex lesion were assessed
      with two additional animals but this lesion did not result in a relearning
      impairment. We therefore suggest that when visuomotor associations have become
      well established through over-training, performance depends on connections
      between the basal ganglia and premotor cortex.

PMID- 15579172
TI  - Benefit of valproic acid in suppressing disease progression of ALS model mice.
AB  - Valproic acid (VPA) has long been used as an antiepileptic drug and recently as a
      mood stabilizer, and evidence is increasing that VPA exerts neuroprotective
      effects through changes in a variety of intracellular signalling pathways
      including upregulation of Bcl-2 protein with an antiapoptotic property and
      inhibiting glycogen synthase kinase 3-beta, which is considered to promote cell
      survival. Although the neuroprotective effects of VPA have been demonstrated in a
      murine model of human immunodeficiency virus-1 encephalitis, there have been no
      reports on the effect of VPA in chronic progressing neurodegenerative disease
      models including amyotrophic lateral sclerosis (ALS). ALS is a devastating
      disease selectively affecting motoneurons, and its disease model mice bear a
      close resemblance to ALS symptomatically and pathologically. First, we used an
      organotypic slice culture using mouse spinal cord, and showed that VPA protected
      spinal motoneurons against death from glutamate toxicity in vitro. Then, we
      treated ALS model mice with VPA at the dose effective level for epileptic model
      mice after 45 days of age (pre-onset treatment) or the day of the disease onset
      (post-onset treatment). We found a significant prolongation of the disease
      duration in ALS model mice in both methods of treatment. Considering the long
      usage of VPA for epileptic patients with good tolerance and safety, these data
      strongly support the clinical application of VPA for ALS treatment.

PMID- 15579173
TI  - Homophilic interactions of chick neurofascin in trans are important for neurite
      induction.
AB  - Neurofascin is a member of the immunoglobulin superfamily involved in axon
      extension and fasciculation. Here we apply adenoviral short hairpin RNA (shRNA)
      expression in primary neurons, PC12-NIH/3T3 co-cultures in combination with
      Luminex assays, to demonstrate homophilic interactions of neurofascin for neurite
      outgrowth. An adenoviral vector was constructed for the expression of shRNA in
      primary tectal cells that inhibits gene expression similar to short interfering
      RNA. We demonstrate that after shRNA-mediated knockdown neuronal neurofascin
      expression is important for neurite outgrowth on a neurofascin substrate. Neurite
      outgrowth assays reveal that neurite formation of PC12 cells is increased when
      neurofascin is overexpressed on both outgrowing PC12 cells and substrate NIH/3T3
      cells, suggesting that neurofascin expression is also sufficient for neurite
      induction. Luminex technology for the analysis of protein-protein interactions
      showed homophilic binding of neurofascin to itself.

PMID- 15579174
TI  - Clozapine-, but not haloperidol-, induced increases in deltaFosB-like
      immunoreactivity are completely blocked in the striatum of mice lacking D3
      dopamine receptors.
AB  - On the basis of anatomical and pharmacological evidence, we have proposed that D3
      receptor antagonism plays a role in the mediation of clozapine-, but not
      haloperidol-, induced immediate-early gene expression in the striatum. To test
      this hypothesis directly, we compared the effects of repeated administration of
      vehicle (8 mL/kg/day), clozapine (20 mg/kg/day) and haloperidol (2 mg/kg/day) for
      17 days on expression of deltaFosB-like immunoreactivity (deltaFosB-Ir) in the
      island of Calleja major, nucleus accumbens and caudate-putamen of wild-type
      C57Bl6 (WT) and D3 receptor knockout (D3KO) mice. In vehicle-treated mice, the
      number of deltaFosB-Ir neurons in the nucleus accumbens was greater in D3KO than
      in WT mice. This finding is consistent with results implicating D3 receptor
      activation in the tonic inhibition of this limbic structure. Unlike rats,
      clozapine significantly increased the number of deltaFosB-Ir neurons in both the
      nucleus accumbens and the caudate-putamen of WT mice albeit to a lesser extent in
      the caudate-putamen than nucleus accumbens. Similar to rats, however, deltaFosB
      Ir in the island of Calleja major of WT mice was elevated by clozapine but not by
      haloperidol. In the nucleus accumbens and caudate-putamen, haloperidol produced
      similar increases in deltaFosB-Ir in WT and D3KO mice. By contrast, clozapine
      induced increases in deltaFosB-Ir in the island of Calleja major, nucleus
      accumbens and caudate-putamen of WT mice were absent in D3KO mice. These
      findings, which indicate that D3 receptor blockade is essential for clozapine
      induced increases in striatal deltaFosB-Ir, suggest that D3 receptor antagonism
      may contribute to the unique therapeutic profile of this atypical antipsychotic.

PMID- 15579175
TI  - GABA-immunoreactive starburst amacrine cells in pigmented and albino rats.
AB  - In this study we tested whether the critical anatomical substrate for retinal
      direction selectivity is altered in albino mammals. We used dual immunostaining
      for GABA and choline acetyltransferase and quantitatively analyzed the number of
      double-labelled starburst amacrine cells in wild-type and albino rats. In albino
      rats, the percentage of ON-amacrine cells with high GABA content was
      significantly lower than in pigmented animals. OFF-amacrines did not
      significantly differ between the two rat strains. Thus, the decreased GABA
      content in ON-amacrine cells could reflect an altered neuronal substrate for
      retinal direction selectivity. These results are discussed in relation to the
      optokinetic deficits described in albino mammals.

PMID- 15579176
TI  - The clock in the dorsal suprachiasmatic nucleus runs faster than that in the
      ventral.
AB  - In mammals, circadian rhythms are driven by a pacemaker located in the
      suprachiasmatic nuclei (SCN) of the hypothalamus. The pacemaker is composed of an
      ensemble of multiple, single-cell oscillators in the SCN. We measured arginine
      vasopressin (AVP) release in organotypic SCN slices. The SCN slice culture showed
      circadian oscillation of AVP release with a period length (+/- SEM) of 23.84 +/-
      00.03 h. This period is very similar to the one we previously reported in
      dispersed SCN cultures and is also close to that of behavioural rhythms. When the
      ventral part was removed by a surgical cut across the slice in the horizontal
      plane, however, the period became shorter (23.22 +/- 00.08 h). On the other hand,
      the removal of the dorsal part did not affect period length. These results
      suggest that the oscillators in ventral and dorsal cells contribute differently
      to period length and that the dorsal oscillators are entrained by the ventral
      ones to form a single integrated oscillator.

PMID- 15579177
TI  - Estrogen attenuates antinociception produced by stimulation of Kolliker-Fuse
      nucleus in the rat.
AB  - This is the first demonstration of sex-related differences in the alpha2
      adrenoceptor-mediated antinociceptive effects produced by stimulation of an
      endogenous noradrenergic pathway. Electrical or chemical (substance P)
      stimulation of Kolliker-Fuse nucleus (KF, A7) is known to produce antinociception
      mediated by alpha2-adrenoceptors in the spinal cord. KF stimulation has also been
      shown to inhibit the responses of nociceptive neurons in the dorsal horn of the
      medulla and the spinal cord. We investigated whether KF stimulation produces sex
      specific modulation of trigeminal nociception. The N-methyl-D-aspartic acid
      (NMDA)-induced nociceptive behavior was employed as an index of nociception.
      Microinjection of NMDA (2 nmol/10 microL) in the trigeminal region produced
      nociceptive scratching behavior that was confined to the orofacial region. Male
      and ovariectomized (OVX) Sprague-Dawley rats were implanted with a guide cannula
      dorsal to the KF nucleus and a PE-10 cannula in the trigeminal region dorsal to
      obex. Nociceptive testing was conducted after 5-7 days of recovery. A group of
      ovariectomized rats (OVX+E) was treated with estradiol benzoate 48 h prior to
      nociceptive testing. There were no significant differences in the number of NMDA
      induced scratches or duration between the male, OVX and OVX+E groups.
      Microinjection of substance P (3.7 pmol/0.5 microL) in the KF significantly
      reduced the number of NMDA-induced scratches and their duration in male and OVX
      groups; these were restored to control levels by yohimbine (30 microg/15 microL),
      an alpha2-adrenoceptor antagonist. However, KF stimulation failed to inhibit the
      NMDA-induced scratching behavior in the OVX+E group. We conclude that stimulation
      of KF produces estrogen-dependent modulation of nociception.

PMID- 15579178
TI  - The effects of recombinant human thyrotropin, in normal subjects and patients
      with goitre.

PMID- 15579179
TI  - Endocrine effects of tobacco smoking.

PMID- 15579180
TI  - A new less-invasive and more informative low-dose ACTH test: salivary steroids in
      response to intramuscular corticotrophin.
AB  - OBJECTIVE: The intravenous low-dose ACTH test has been proposed as a sensitive
      tool to assess adrenal function through circulating steroids. The aims of this
      study were to: (a) find the minimal intramuscular ACTH dose that induced serum
      and salivary cortisol and aldosterone responses equivalent to those obtained
      after a pharmacological dose of ACTH; and (b) define the minimum normal salivary
      cortisol and aldosterone responses in healthy subjects to that dose of ACTH. We
      also compared the performances of the standard- and low-dose ACTH intramuscular
      tests to screen patients with known hypothalamo-pituitary-adrenal impairments.
      DESIGN: Rapid ACTH tests were performed in individuals using various
      intramuscular doses (12.5, 25 and 250 microg) at 2-week intervals. SUBJECTS:
      Twenty-one healthy volunteers and 19 patients with primary (nine cases) and
      secondary (10 cases) adrenal insufficiency. MEASUREMENT: Serum and salivary
      cortisol and aldosterone concentrations were measured at baseline and after ACTH.
      Serum cortisol > or = 552.0 nmol/l and aldosterone > or = 555.0 pmol/l
      concentrations at 30 min after 250 microg of ACTH were defined as normal
      responses. RESULTS: In healthy volunteers cortisol and aldosterone responded to
      ACTH in a dose-dependent manner. The time to peak in saliva for each steroid was
      delayed as the dose of ACTH increased. The minimum ACTH dose that produced
      equivalent steroid responses at 30 min to 250 microg of ACTH (standard-dose test;
      SDT) was 25 microg (low-dose test; LDT). Saliva collection 30 min after LDT and
      SDT showed cortisol and aldosterone concentrations of at least 20.0 nmol/l and
      100.0 pmol/l, respectively. These values were defined as normal steroid
      responses. Blunted salivary steroid responses to LDT and SDT were found in all
      patients with primary adrenal insufficiency. Subnormal salivary cortisol levels
      in response to LDT and SDT were found in all patients with secondary adrenal
      insufficiency. In five patients full recovery of adrenal function was
      demonstrated by both tests after steroid withdrawal. In the follow-up of four
      patients studied during the recovery period, subnormal SAF response after LDT and
      normal after SDT was demonstrated. Preservation of the adrenal glomerulosa was
      found in all the patients with secondary adrenal insufficiency through the normal
      rise in salivary aldosterone after both LDT and SDT. CONCLUSIONS: Adrenal
      function can be accurately investigated with simultaneous measurements of
      salivary cortisol and aldosterone in response to 25 microg of corticotrophin
      injected into the deltoid muscle. Our data suggest that this may become a useful
      and relatively noninvasive clinical tool to detect subclinical hypoadrenal
      states.

PMID- 15579181
TI  - Survivors of childhood acute lymphoblastic leukaemia, with radiation-induced GH
      deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected
      by 12 months of GH treatment.
AB  - OBJECTIVE: Adult survivors of childhood acute lymphoblastic leukaemia (ALL) often
      exhibit GH deficiency (GHD), due to prophylactic cranial radiotherapy (CRT). It
      is not known whether the observed risk for adiposity in these patients is
      associated with impaired insulin sensitivity and whether the insulin sensitivity
      is affected by GH replacement therapy. SUBJECTS AND DESIGN: Eleven patients with
      GHD (median age 29 years), previously given prophylactic CRT for ALL, and 11 sex
      , age- and body mass index (BMI)-matched controls were investigated with
      bioimpedance analysis (BIA) and analysis of serum leptin, serum free fatty acids
      (FFA) and serum insulin. Insulin sensitivity was measured by a euglycaemic
      hyperinsulinaemic clamp technique (IS-clamp). Moreover, the effects of 12 months
      of individually titrated GH treatment (median dose 0.5 mg/day) on these
      parameters were investigated. RESULTS: At baseline, the patients had lower fat
      free mass (FFM) (P = 0.003), higher percentage fat mass (FM) (P = 0.05), serum
      insulin (P = 0.02) and serum leptin/kg FM (P = 0.01) than controls. The patients
      had a tendency towards impaired IS-clamp (P = 0.06), which disappeared after
      correction for body composition (IS-clamp/kg FFM; P > 0.5). In the patients, time
      since CRT was positively correlated with percentage FM (r = 0.70, P = 0.02), and
      there was an independent negative association between serum FFA and IS-clamp (P =
      0.05). Twelve months of GH treatment increased serum IGF-I (P = 0.003) and FFM (P
      = 0.02) and decreased percentage FM (P = 0.03), but no significant changes were
      seen in serum leptin/kg FM, serum FFA, FFA-clamp, serum insulin or IS-clamp (all,
      P > or = 0.2). CONCLUSIONS: Young adult survivors of childhood ALL with GHD had
      increased fat mass, hyperleptinaemia and impaired insulin sensitivity, which
      could be a consequence of radiation-induced impairment of GH secretion or
      mediated by other hypothalamic dysfunctions, such as leptin resistance or other
      unknown factors, affected by CRT. Twelve months of individualized GH replacement
      therapy led to positive effects on body composition, but the hyperleptinaemia,
      hyperinsulinaemia and the impaired insulin sensitivity remained unchanged.

PMID- 15579182
TI  - Changed bone status in human immunodeficiency virus type 1 (HIV-1) perinatally
      infected children is related to low serum free IGF-I.
AB  - INTRODUCTION: Adults and children affected by human immunodeficiency virus type-1
      (HIV-1) infection show bone demineralization. Little is known about skeletal
      status using a quantitative high-frequency ultrasound (QUS) technique in these
      patients. OBJECTIVE: To evaluate the bone quality and assess the role of the IGF
      system in the bone metabolism and skeletal status of HIV-1 perinatally infected
      children. PATIENTS AND METHODS: Serum free and total IGF-I, IGFBP-3, serum
      osteocalcin level, urinary deoxypyridinoline concentration, spontaneous
      interleukin-6 (IL-6) release and broadband ultrasound attenuation (BUA) were
      evaluated in 44 prepubertal children who had perinatal HIV-1 infection. The
      patients were divided into two groups depending on the severity of their clinical
      condition: group 1 (23 children with no or mild clinical symptoms, mean age 8.0
      +/- 2.9 years) and group 2 (21 children with severe clinical symptoms, mean age
      8.58 +/- 2.47 years). Fifty-five healthy age- and sex-matched controls were
      analysed for comparison. RESULTS: Compared with group 1 and the controls, group 2
      patients showed a significantly reduced BUA Z-score (P < 0.001), and
      significantly reduced concentrations of serum osteocalcin (P < 0.001) and urinary
      deoxypyridinoline (P < 0.001 and P < 0.05, respectively). Group 2 patients also
      showed significantly reduced serum free IGF-I (P < 0.001) and total IGF-I (P <
      0.05) levels compared with the controls, but not with group 1. No statistically
      significant differences were found between the three groups with regard to IGFBP
      3. Group 2 patients showed significantly higher spontaneous IL-6 release than
      group 1 patients and controls (P < 0.001). BUA Z-scores displayed a significant
      correlation with free IGF-I in group 2 (r = 0.96; P < 0.001), group 1 (r = 0.56;
      P = 0.005) and controls (r = 0.50; P < 0.001). CONCLUSION: Our study shows that
      only patients affected by perinatal HIV-1 infection with severe clinical
      manifestations present significant changes in bone quality and bone metabolism.
      Our data also show that impairment of skeletal status is related to reduction in
      serum total and free IGF-I. Children with perinatal HIV-1 infection, because of a
      considerable improvement in life expectancy, seem at great risk of not obtaining
      an optimal bone mass. A possible therapeutic approach should be considered in
      these children.

PMID- 15579183
TI  - Decreased plasma adiponectin concentrations are closely associated with
      nonalcoholic hepatic steatosis in obese individuals.
AB  - OBJECTIVES: To evaluate whether subjects with nonalcoholic hepatic steatosis (HS)
      differed in their circulating adiponectin levels compared with those in subjects
      without HS and, if so, to examine to what extent such differences are mediated by
      the adverse pattern of the metabolic syndrome variables, typically observed in
      these subjects. DESIGN AND PATIENTS: In a cross-sectional study, we analysed 68
      healthy, mildly obese individuals with a negative or negligible daily alcohol
      consumption. MEASUREMENTS: HS (by ultrasonography), glucose tolerance status (by
      oral glucose load), insulin resistance [by homeostasis model assessment (HOMA)],
      and plasma adiponectin concentration [by enzyme-linked immunosorbent assay
      (ELISA)] were measured. RESULTS: Subjects with nonalcoholic HS (n = 43) had
      markedly lower plasma adiponectin concentrations than those without HS (n = 25)
      (5.6 +/- 3 vs. 10.8 +/- 4 microg/ml; P < 0.001). In addition, the former had
      significantly higher values for body mass index (BMI), waist/hip ratio (WHR),
      HOMA-insulin resistance score, plasma insulin (at fasting and after glucose
      load), plasma triglyceride and liver enzyme concentrations [such as alanine
      aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT)], and tended to
      have lower high density lipoprotein (HDL) cholesterol concentration. The
      significant differences in plasma adiponectin levels that were observed between
      the groups were little affected by adjustment for potential confounding
      variables, such as age, sex, BMI, WHR, lipids and HOMA-insulin resistance score.
      Similarly, in multivariate regression analyses, hypoadiponectinaemia
      significantly predicted the presence of HS (P < 0.001) and the increased levels
      of GGT and ALT (P < 0.05), independently of potential confounders. CONCLUSIONS:
      These results show that decreased plasma adiponectin concentrations are closely
      correlated with nonalcoholic HS in healthy obese individuals.

PMID- 15579184
TI  - Are there disadvantages in administering 131I ablation therapy in patients with
      differentiated thyroid carcinoma without a preablative diagnostic 131I whole-body
      scan?
AB  - OBJECTIVE: To evaluate the risk of performing inappropriate (131)I ablative
      therapies for thyroid carcinoma in patients lacking thyroid remnants or
      metastases, using a strategy of treatment without a preliminary iodine-131
      diagnostic whole-body scan (DxWBS). DESIGN: Retrospective evaluation of post
      therapy whole-body scans to assess the prevalence of thyroid remnants or
      metastases after total thyroidectomy. Comparison of (131)I uptake test and
      thyroglobulin (Tg) off levothyroxine (L-T4) performed before therapy with post
      therapy scans, in order to evaluate the ability to predict inappropriate
      treatments. PATIENTS: A group of 875 consecutive patients with previous total or
      near-total thyroidectomy for differentiated thyroid carcinoma underwent (131)I
      ablative therapy without a preliminary (131)I-DxWBS. All patients were clinically
      free of distant metastases and macroscopic residual tumour. MEASUREMENTS: Whole
      body scans were performed 2-5 days after the treatment as gold standard for
      thyroid remnants and metastases; 24-h (131)I quantitative neck uptake test and Tg
      off L-T4 were performed before (131)I therapy. RESULTS: The majority of patients
      (94%) were found to have thyroid remnants or metastases at post-therapy scans, in
      most cases (91.2%) with detectable Tg off L-T4 and positive 24-h neck uptake. 14
      patients (1.6%) with tiny lymph-node metastases positive at post-therapy scans
      showed undetectable Tg off L-T4. In 30 patients (3.6%) faint positive post
      therapy images for thyroid remnants have been classified as false-positive
      results on the basis of both negative 24-h neck uptake and undetectable Tg off L
      T4. CONCLUSIONS: This study confirms that most patients have residual thyroid
      tissue after total thyroidectomy and that it seems reasonable to omit routine
      diagnostic whole-body scans before (131)I treatment with clinical, managerial and
      economic advantages.

PMID- 15579185
TI  - Relationship of nonalcoholic hepatic steatosis to overnight low-dose
      dexamethasone suppression test in obese individuals.
AB  - OBJECTIVES: To examine the association between nonalcoholic hepatic steatosis
      (HS) and the activity of the hypothalamo-pituitary-adrenal (HPA) axis, as
      evaluated by a low-dose dexamethasone suppression test, in obese subjects. DESIGN
      AND PATIENTS: In a cross-sectional study, we examined 54 obese, otherwise
      healthy, individuals with a negligible or zero daily alcohol consumption.
      MEASUREMENTS: HS (by ultrasonography), glucose tolerance status (by oral glucose
      load), insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg
      postdexamethasone (postdex) suppression cortisol levels were measured. RESULTS:
      Subjects with nonalcoholic HS (n = 39) had markedly less suppressed circulating
      cortisol levels than those without HS (n = 15) (21.9 +/- 2.6 vs. 11.0 +/- 1.4
      nmol/l, P < 0.001). In addition, subjects with nonalcoholic HS had significantly
      higher values of HOMA-insulin resistance score and circulating liver enzymes than
      their counterparts without HS. Age, body mass index (BMI), waist/hip ratio,
      plasma glucose concentration (both at fasting and after glucose load), lipids and
      blood pressure values did not differ significantly between the groups. Females
      were more represented among those without HS. The marked differences in postdex
      suppression cortisol levels that were observed between the groups were little
      affected by adjustment for sex, age, BMI, waist/hip ratio, HOMA-insulin
      resistance score, plasma lipids and liver enzyme levels. Similarly, in a logistic
      regression analysis, cortisol levels significantly predicted the presence of
      nonalcoholic HS (P = 0.032), independently of potential confounders. CONCLUSIONS:
      These results suggest that nonalcoholic hepatic steatosis is closely correlated
      with a subtle, chronic activation of the HPA axis in obese, otherwise healthy,
      individuals.

PMID- 15579186
TI  - Genomic structure of the human gene for protein kinase A regulatory subunit R1
      beta (PRKAR1B) on 7p22: no evidence for mutations in familial hyperaldosteronism
      type II in a large affected kindred.
AB  - OBJECTIVE: Familial hyperaldosteronism type II (FH-II) is characterized by
      inheritance of primary aldosteronism (PAL) but, unlike FH-I, is not
      glucocorticoid remediable and not associated with the hybrid CYP11B1/CYP11B2 gene
      mutation. Analysis of two pedigrees previously demonstrated linkage of FH-II with
      a locus at chromosome 7p22. We sought to determine whether mutations in the exons
      or intron/exon boundaries in PRKAR1B (encoding protein kinase A regulatory
      subunit R1-beta), which resides within the linked locus, are associated with FH
      II. METHODS: Primers enabling sequencing of all exons and intron/exon boundaries
      were designed by BLAT search using known mRNA sequence, and comparison with an
      orthologous mouse gene. Sequences from four affected and two unaffected subjects
      from an Australian family with FH-II demonstrating linkage at 7p22 were compared
      with published sequences. RESULTS: A probable two-nucleotide GenBank sequence
      error, resulting in an amino acid change, was detected. Two of seven single
      nucleotide polymorphisms (SNPs) identified were in exons and five in introns.
      Neither exon-localized SNP resulted in an amino acid change. All intron-localized
      SNPs were at least 16 nucleotides from the closest intron/exon boundary and
      therefore unlikely to interfere with gene splicing. Importantly, none of the
      identified SNPs was exclusively associated with affectation status. CONCLUSIONS:
      Mutations in the exons or intron/exon boundaries of PRKAR1B do not appear to be
      responsible for FH-II in this family, but a mutation in the promoter or remaining
      intronic or 5' or 3' untranslated regions could be. Alternatively, a mutation
      within another gene residing at the 7p22 locus may be responsible.

PMID- 15579187
TI  - Insulin sensitivity and coronary vasoreactivity: insulin sensitivity relates to
      adenosine-stimulated coronary flow response in human subjects.
AB  - OBJECTIVE: Diabetes is associated with coronary microvasculature abnormalities
      and impaired coronary flow reserve (CFR). CFR is the ratio of coronary flow under
      maximal vasodilation to basal flow and is a measure for coronary vasoreactivity.
      Insulin resistance is the central defect in the development of type 2 diabetes,
      preceding its onset by 10-20 years. Thus, the relationship between insulin
      sensitivity and CFR in nondiabetic subjects is particularly interesting. The aim
      of the study was to investigate this relationship. DESIGN: Cross-sectional study.
      PATIENTS: The study population consisted of 18 nondiabetic subjects without
      coronary artery stenosis on coronary angiography. We excluded patients with
      structural heart disease or with conditions affecting CFR or insulin sensitivity
      such as low density lipoprotein (LDL)-cholesterol > or = 4.14 mmol/l, smoking,
      hypertension or obesity with a body mass index (BMI) > 28 kg/m(2). MEASUREMENTS
      AND RESULTS: CFR was 3.1 +/- 0.8 (range 1.7-4.8), as assessed by intracoronary
      Doppler measurements in the left anterior descending coronary arteries after
      adenosine stimulation. Intravascular ultrasound revealed zero to moderate
      coronary atherosclerotic changes. Whole-body insulin sensitivity (M-value) was
      7.5 +/- 2.9 mg/kg/min (range 2.2-12.6), as assessed by the hyperinsulinaemic
      euglycaemic clamp test. Subjects with low CFR (< 3.0) had a significantly lower M
      value than subjects with normal CFR (> 3.0) (6.0 +/- 2.5 vs. 9.0 +/- 2.5
      mg/kg/min, P = 0.021). Univariate linear regression demonstrated a strong
      correlation between CFR and M-value (r = 0.76, P < 0.001). In multiple regression
      analysis, the significant association of CFR with M-value was independent of
      potential confounders (sex, age, BMI, LDL-cholesterol and plaque burden on
      intravascular ultrasound). Bootstrap analysis corroborated this finding.
      CONCLUSIONS: Whole-body insulin sensitivity relates to coronary vasoreactivity.
      Across a wide range of both insulin sensitivity and coronary flow reserve from
      markedly abnormal to normal values, an increase in insulin sensitivity appears to
      be associated with an increase in coronary flow reserve. Insulin resistance is
      therefore associated with coronary microvasculature abnormalities in
      nondiabetics.

PMID- 15579188
TI  - Utility of fine-needle aspiration for diagnosis of carcinoma associated with
      multinodular goitre.
AB  - BACKGROUND: Fine-needle aspiration (FNA) is a useful method for evaluating a
      solitary thyroid nodule; however, this is not an agreed method for a multinodular
      goitre (MNG). The aim of this study was to assess the utility of preoperative FNA
      for detecting malignancy in MNG. PATIENTS AND METHOD: We analysed operated MNGs
      in which FNA had been performed. Puncture was carried out on the dominant nodule
      and any other nodules with features suggesting malignancy. The diagnosis was
      classed as colloid, follicular or Hurthle proliferation, suggestive of
      malignancy, haematic and inadequate. The thyroid FNA results, grouped into
      suggestive of malignancy (positive result) and other diagnoses (negative result),
      were compared to those of the final histological study in order to calculate the
      value of the test in diagnosing malignancy. RESULTS: FNA was performed in 432
      MNGs, of which 42 (9.7%) were associated with carcinoma. Overall, the results of
      the test were poor, revealing a sensitivity of 17%, specificity of 96% and
      diagnostic accuracy of 88%, with a positive predictive value of 32% and negative
      predictive value of 88%. When the values were recalculated with the exclusion of
      microcarcinomas--considering their minor clinical importance--there was a slight
      improvement in the results: the sensitivity increased to 26%, diagnostic accuracy
      to 93% and negative predictive value to 96%. However, the specificity remained at
      96%, and the positive predictive value fell from 32% to 25%. The results of the
      test improved in multifocal carcinomas. CONCLUSIONS: Thyroid fine needle
      aspiration is not useful for differentiating MNG with malignant degeneration from
      benign MNG, as more than 80% of carcinomas go unnoticed; it provides a
      sensitivity of 17% for detecting carcinomas, rising to 26% if microcarcinomas are
      excluded. We therefore suggest that clinical criteria should prevail over FNA.

PMID- 15579189
TI  - Adiponectin is independently associated with insulin sensitivity in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: The polycystic ovary syndrome (PCOS) is associated with obesity and
      insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis.
      Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and
      putative antiatherosclerotic properties. The aim of the study was to elucidate
      determinants of circulating adiponectin levels and to investigate the potential
      role of adiponectin in insulin resistance in PCOS women. PATIENTS AND
      MEASUREMENTS: Plasma adiponectin and parameters of obesity, insulin resistance
      and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female
      controls. RESULTS: Both in PCOS and controls, adiponectin levels were lower in
      overweight or obese women than in normal-weight women, without any difference
      between PCOS and controls after adjustment for body mass index (BMI). In PCOS and
      in controls there was a significant correlation of adiponectin with BMI (r = 
      0.516, P < 0.001), fasting insulin (r = -0.404, P < 0.001), homeostasis model
      sensitivity (HOMA %S) (r = -0.424, P < 0.001) and testosterone (r = -0.279, P <
      0.01), but no correlation with androstenedione (r = -0.112, P = 0.325), 17-OH
      progesterone (r =-0.031, P = 0.784) or the LH/FSH ratio (r =-0.033, P = 0.753).
      Multiple linear regression analysis revealed that BMI and HOMA %S but not
      testosterone were independently associated with adiponectin plasma levels,
      explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin,
      respectively. In PCOS patients insulin sensitivity, as indicated by continuous
      infusion of glucose with model assessment (CIGMA %S) was significantly correlated
      with adiponectin (r = 0.55; P < 0.001), BMI (r =-0.575; P < 0.001), waist-to-hip
      ratio (WHR) (r =-0.48; P = 0.001), body fat mass assessed by dual-energy X-ray
      absorptiometry (DEXA) [Dexa-fat (total) (r = -0.61; P < 0.001) and Dexa-fat
      (trunk) (r = -0.59; P < 0.001)] and with testosterone (r = -0.42; P = 0.001).
      Multiple linear regression analysis demonstrated that markers of obesity such as
      BMI, total or truncal fat mass, age and adiponectin were independently associated
      with CIGMA %S, and that circulating adiponectin accounted for about 18% of the
      degree of insulin resistance in PCOS. By contrast, testosterone was not a
      significant factor, suggesting that PCOS per se did not affect insulin
      sensitivity independent from obesity, age and adiponectin. Metformin treatment
      for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma
      adiponectin (P = 0.59) despite significant loss of weight and fat mass and
      improvement in hyperandrogenaemia. CONCLUSIONS: PCOS per se is not associated
      with decreased levels of plasma adiponectin. However, circulating adiponectin is
      independently associated with the degree of insulin resistance in PCOS women and
      may contribute to the development and/or maintenance of insulin resistance
      independent from adiposity.

PMID- 15579190
TI  - Acute management of pituitary apoplexy--surgery or conservative management?
AB  - BACKGROUND AND OBJECTIVE: The rarity of pituitary apoplexy renders it a difficult
      subject for audit; hence there are no evidence-based standards of optimum care
      for such patients. The key controversy in management relates to the role of acute
      neurosurgical intervention. In recent years we have adopted a relatively
      conservative approach towards patients presenting with pituitary apoplexy.
      Against this background, we aimed to determine whether our less-interventional
      approach affected long-term clinical outcome in these patients. PATIENTS AND
      DESIGN: A retrospective analysis was performed to evaluate clinical presentation,
      management and clinical outcomes in a cohort of patients who presented acutely
      with pituitary apoplexy during the period 1994-2004. Data from 33 patients (13
      female) were included, with a mean age of 52 (range 27-79) years and mean follow
      up duration of 3.7 (0.4-10.1) years. RESULTS: The most common presenting symptoms
      were headache (97%), visual deficits (82%) and nausea/vomiting (78%). Fifteen
      patients (46%) underwent transsphenoidal surgery while 18 were managed
      conservatively. Indications for surgery were deteriorating visual deficit (n =
      13), hemiparesis (n = 1) and altered conscious level (n = 1). Eight patients in
      the surgical group had ocular paresis that resolved in 63% following surgery, and
      seven had visual field defects with recovery in 57% postsurgery. Conservative
      management was reserved for patients with absent, or evidence of resolving,
      visual deficits at presentation. In this group, seven presented initially with
      ocular paresis and six with visual field defects but all made full recoveries. Of
      the patients managed neurosurgically, 87% required long-term glucocorticoid
      replacement and 60% required long-term thyroid hormone replacement.
      Conservatively managed patients required glucocorticoid replacement in 72% and
      thyroid hormone replacement in 72% of cases (P = NS between the two groups). Sex
      steroid replacement was required in 67% and 83% of patients managed
      neurosurgically and conservatively respectively (P = NS). At latest follow-up one
      patient in the conservatively managed group had required surgery and one in the
      surgically managed group had received pituitary radiotherapy, in both instances
      due to evidence of tumour regrowth on magnetic resonance imaging (MRI).
      CONCLUSION: Our findings suggest that patients presenting with pituitary apoplexy
      in whom visual deficits are stable or improving may be managed expectantly as
      there is no identifiable deleterious effect on visual or endocrine outcome. One
      patient from each group experienced tumour regrowth that necessitated further
      treatment intervention, highlighting the importance of long-term follow-up in
      patients with pituitary apoplexy.

PMID- 15579191
TI  - Correlations of adiponectin level with insulin resistance and atherosclerosis in
      Japanese male populations.
AB  - OBJECTIVE: Adiponectin, which is secreted specifically by adipose tissue, has
      been shown to have an anti-atherosclerotic effect and to improve insulin
      resistance. The aim of this study was to determine the correlations of plasma
      adiponectin concentration with insulin resistance and atherosclerosis. DESIGN AND
      METHODS: We investigated the relationships of adiponectin concentration with
      insulin sensitivity, high-sensitivity C-reactive protein (hCRP) and pulse wave
      velocity (PWV) in male inhabitants of rural communities in Japan. hCRP and PWV
      were used as an indexes of atherosclerosis. RESULTS: A negative correlation was
      found between homeostasis model assessment (HOMA) as an index of insulin
      resistance and adiponectin concentration. Results of stepwise regression analysis
      for adiponectin showed that age, HOMA and serum triglyceride (TG) were
      independently correlated with adiponectin. Multiple regression analysis for lipid
      profile was also performed and revealed that adiponectin and HOMA were
      independently correlated with TG and serum high density lipoprotein (HDL)
      cholesterol but not with serum total cholesterol. A significant negative
      correlation was found between adiponectin and hCRP in all subjects, and a
      significant negative correlation between adiponectin and PWV was also found in
      subjects equal or less than 70 years old. When HOMA was added to this analysis,
      HOMA was found to be independently correlated with hCRP and PWV, but the
      adiponectin level did not appear to be a significant predictor of hCRP or PWV.
      CONCLUSIONS: The results suggest that adiponectin plays a role in lipid
      metabolism and correlates with atherosclerosis either directly or through insulin
      resistance.

PMID- 15579192
TI  - Progestogens of varying androgenicity and cardiovascular risk factors in
      postmenopausal women receiving oestrogen replacement therapy.
AB  - OBJECTIVE: Medroxyprogesterone (MP) was used as the progestogen in randomized
      clinical trials of postmenopausal hormone replacement on cardiovascular risk. To
      attempt to understand the lack of benefit in these trials, we have examined the
      effects of MP and two other progestogens, the less androgenic desogestrel (DG)
      and the more androgenic norethisterone (NE), on cardiovascular risk factors
      against a background of oestrogen therapy. DESIGN AND MEASUREMENTS: Thirty-four
      women were treated with conjugated equine oestrogens (CEE) 0.625 mg daily alone
      for 12 weeks, followed in random order by each of the three progestogens (DG 75
      microg, MP 10 mg and NE 1 mg daily) given sequentially for three 12-week cycles
      while maintaining the same CEE treatment. We measured serum lipoproteins,
      paraoxonase activity, C-reactive protein (CRP), fibrinogen, fasting glucose and
      insulin levels at baseline, at the end of the oestrogen-only phase and at the end
      of each of the combined oestrogen and progestogen phases. RESULTS: The addition
      of progestogens to CEE maintained the oestrogen-induced reduction in
      apolipoprotein B (apo B) and lipoprotein (a) [Lp(a)], and further lowered total
      cholesterol (P < 0.01) and fibrinogen (P < 0.001). CEE raised serum triglyceride
      (P < 0.001) and CRP (P < 0.01) concentrations, which reverted towards pre
      oestrogen levels with progestogens. Progestogens significantly reduced high
      density lipoprotein (HDL) cholesterol (P < 0.05). NE was associated with the
      greatest reduction in HDL cholesterol and apo A1, but was most effective in
      preserving paraoxonase activity and reducing the potentially unfavourable
      oestrogen-induced increases in triglycerides and CRP. CONCLUSION: Preconceptions
      that more androgenic progestogens necessarily have more unfavourable effects on
      cardiovascular risk factors may require revision.

PMID- 15579193
TI  - High cardiovascular risk in patients with Cushing's syndrome according to 1999
      WHO/ISH guidelines.
AB  - OBJECTIVE: In patients with Cushing's syndrome (CS) cardiovascular complications
      determine a mortality rate four times higher than in an age- and gender-matched
      population. Therefore, we calculated the global cardiovascular risk in patients
      with CS. DESIGN AND PATIENTS: We applied the World Health Organization-
      International Society of Hypertension (WHO/ISH) 1999 guidelines for the
      estimation of cardiovascular risk in 38 females and 11 males with CS; 27
      pituitary adenomas, 15 adrenal adenomas, four adrenal carcinomas and three
      ectopic ACTH-secreting tumours. The risk of major cardiovascular events was
      estimated considering the combined effect of several risk factors (hypertension,
      diabetes, etc.), organ damage (left ventricular hypertrophy (LVH), proteinuria,
      etc.) and associated pathologies. Four categories of absolute cardiovascular
      disease risk were defined (low, medium, high, very high). RESULTS: Eighty per
      cent of patients presented a 'high' or 'very high' cardiovascular risk; 85.1% of
      the patients were hypertensive with a mild-moderate hypertension (68%). Forty
      seven per cent of patients were diabetics and 41.3% were obese. Hyperlipidaemia
      was less frequent (37.5%). Fasting glycaemia was the only cardiovascular risk
      factor that correlated with a degree of hypercortisolism. Duration of disease
      correlated with the presence of obesity (P < 0.0008) and hypertension (P < 0.03)
      but not with the presence of diabetes or dyslipidaemia and seemed to be the only
      significant predictor of cardiovascular risk (P = 0.03). CONCLUSIONS: Patients
      with active CS present a remarkably increased cardiovascular risk. Considering
      that the biochemical cure of hypercortisolism is often difficult to obtain,
      especially in Cushing's disease, and that cardiovascular risk could persist even
      after the 'cure', control of risk factors should be one of the primary goals of
      the therapy.

PMID- 15579194
TI  - Adequacy of information delivered to patients during consultation for
      thyrotoxicosis.

PMID- 15579195
TI  - Prepubertal gynaecomastia caused by medication or the aromatase excess syndrome.

PMID- 15579196
TI  - Identification and functional analysis of a novel inactivating mutation (A804D)
      of the calcium-sensing receptor gene.

PMID- 15579197
TI  - Can gene expression profiling predict survival for patients with squamous cell
      carcinoma of the lung?
AB  - BACKGROUND: Lung cancer remains to be the leading cause of cancer death
      worldwide. Patients with similar lung cancer may experience quite different
      clinical outcomes. Reliable molecular prognostic markers are needed to
      characterize the disparity. In order to identify the genes responsible for the
      aggressiveness of squamous cell carcinoma of the lung, we applied DNA microarray
      technology to a case control study. Fifteen patients with surgically treated
      stage I squamous cell lung cancer were selected. Ten were one-to-one matched on
      tumour size and grade, age, gender, and smoking status; five died of lung cancer
      recurrence within 24 months (high-aggressive group), and five survived more than
      54 months after surgery (low-aggressive group). Five additional tissues were
      included as test samples. Unsupervised and supervised approaches were used to
      explore the relationship among samples and identify differentially expressed
      genes. We also evaluated the gene markers' accuracy in segregating samples to
      their respective group. Functional gene networks for the significant genes were
      retrieved, and their association with survival was tested. RESULTS: Unsupervised
      clustering did not group tumours based on survival experience. At p < 0.05, 294
      and 246 differentially expressed genes for matched and unmatched analysis
      respectively were identified between the low and high aggressive groups. Linear
      discriminant analysis was performed on all samples using the 27 top unique genes,
      and the results showed an overall accuracy rate of 80%. Tests on the association
      of 24 gene networks with study outcome showed that 7 were highly correlated with
      the survival time of the lung cancer patients. CONCLUSION: The overall gene
      expression pattern between the high and low aggressive squamous cell carcinomas
      of the lung did not differ significantly with the control of confounding factors.
      A small subset of genes or genes in specific pathways may be responsible for the
      aggressive nature of a tumour and could potentially serve as panels of prognostic
      markers for stage I squamous cell lung cancer.

PMID- 15579198
TI  - Identification of proteins in laser-microdissected small cell numbers by SELDI
      TOF and Tandem MS.
AB  - BACKGROUND: Laser microdissection allows precise isolation of specific cell types
      and compartments from complex tissues. To analyse proteins from small cell
      numbers, we combine laser-microdissection and manipulation (LMM) with mass
      spectrometry techniques. RESULTS: Hemalaun stained mouse lung sections were used
      to isolate 500-2,000 cells, enough material for complex protein profiles by SELDI
      TOF MS (surface enhanced laser desorption and ionization/time of flight mass
      spectrometry), employing different chromatographic ProteinChip Arrays. Initially,
      to establish the principle, we identified specific protein peaks from 20,000
      laser-microdissected cells, combining column chromatography, SDS-PAGE, tryptic
      digestion, SELDI technology and Tandem MS/MS using a ProteinChip Tandem MS
      Interface. Secondly, our aim was to reduce the labour requirements of
      microdissecting several thousand cells. Therefore, we first defined target
      proteins in a few microdissected cells, then recovered in whole tissue section
      homogenates from the same lung and applied to these analytical techniques. Both
      approaches resulted in a successful identification of the selected peaks.
      CONCLUSION: Laser-microdissection may thus be combined with SELDI-TOF MS for
      generation of protein marker profiles in a cell-type- or compartment-specific
      manner in complex tissues, linked with mass fingerprinting and peptide sequencing
      by Tandem MS/MS for definite characterization.

PMID- 15579199
TI  - Neurotrophin and Trk expression by cells of the human lamina cribrosa following
      oxygen-glucose deprivation.
AB  - BACKGROUND: Ischemia within the optic nerve head (ONH) may contribute to retinal
      ganglion cell (RGC) loss in primary open angle glaucoma (POAG). Ischemia has been
      reported to increase neurotrophin and high affinity Trk receptor expression by
      CNS neurons and glial cells. We have previously demonstrated neurotrophin and Trk
      expression within the lamina cribrosa (LC) region of the ONH. To determine if
      ischemia alters neurotrophin and Trk protein expression in cells from the human
      LC, cultured LC cells and ONH astrocytes were exposed to 48 hours of oxygen
      glucose deprivation (OGD). Also cells were exposed to 48 hours of OGD followed by
      24 hours of recovery in normal growth conditions. Cell number, neurotrophin and
      Trk receptor protein expression, neurotrophin secretion, and Trk receptor
      activation were examined. RESULTS: Cell number was estimated using an assay for
      cell metabolism following 24, 48 and 72 hours of OGD. A statistically significant
      decrease in LC and ONH astrocyte cell number did not occur until 72 hours of OGD,
      therefore cellular protein and conditioned media were collected at 48 hours OGD.
      Protein expression of NGF, BDNF and NT-3 by LC cells and ONH astrocytes increased
      following OGD, as did NGF secretion. Recovery from OGD increased BDNF protein
      expression in LC cells. In ONH astrocytes, recovery from OGD increased NGF
      protein expression, and decreased BDNF secretion. Trk A expression and activation
      in LC cells was increased following OGD while expression and activation of all
      other Trk receptors was decreased. A similar increase in Trk A expression and
      activation was observed in ONH astrocytes following recovery from OGD.
      CONCLUSIONS: In vitro conditions that mimic ischemia increase the expression and
      secretion of neurotrophins by cells from the ONH. Increased Trk A expression and
      activation in LC cells following OGD and in ONH astrocytes following recovery
      from OGD suggest autocrine/paracrine neurotrophin signaling could be a response
      to ONH ischemia in POAG. Also, the increase in NGF, BDNF and NT-3 protein
      expression and NGF secretion following OGD also suggest LC cells and ONH
      astrocytes may be a paracrine source of neurotrophins for RGCs.

PMID- 15579200
TI  - TGF beta1 and PDGF AA override collagen type I inhibition of proliferation in
      human liver connective tissue cells.
AB  - BACKGROUND: A marked expansion of the connective tissue population and an
      abnormal deposition of extracellular matrix proteins are hallmarks of chronic and
      acute injuries to liver tissue. Liver connective tissue cells, also called
      stellate cells, derived from fibrotic liver have been thoroughly characterized
      and correspond phenotypically to myofibroblasts. They are thought to derive from
      fat-storing Ito cells in the perisinusoidal space and acquire a contractile
      phenotype when activated by tissue injury. In the last few years it has become
      evident that several peptide growth factors such as PDGF AA and TGF-beta are
      involved in the development of fibrosis by modulating myofibroblast proliferation
      and collagen secretion. The fact that during the development of chronic fibrosis
      there is concomitant deposition of collagen, a known inhibitory factor, and
      sustained cell proliferation, raises the possibility that stellate cells from
      chronic liver fibrosis patients fail to respond to normal physiologic controls.
      METHODS: In this study we address whether cells from fibrotic liver patients
      respond to normal controls of proliferation. We compared cell proliferation of
      primary human liver connective tissue cells (LCTC) from patients with liver
      fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV;
      TGF-beta, PDGF AA and combinations of collagen type I and TGF-beta or PDGF AA.
      RESULTS: Our results indicate that despite displaying normal contact and collagen
      induced inhibition of proliferation LCTC respond more vigorously to lower
      concentrations of PDGF AA. In addition, we show that collagen type I synergizes
      with growth factors to promote mitogenesis of LCTC but not SF. CONCLUSIONS: The
      synergistic interaction of growth factors and extracellular matrix proteins may
      underlie the development of chronic liver fibrosis.

PMID- 15579201
TI  - Androgen-induced cerebral venous sinus thrombosis in a young body builder: case
      report.
AB  - BACKGROUND: Cerebral venous sinus thrombosis is an infrequent disease with a
      variety of causes. Pregnancy, puerperium, contraceptive pills and intracranial
      infections are the most common causes. The patient may present with headache,
      focal neurological deficits and seizures.The clinical outcome is highly variable
      and treatment with heparin is advised. CASE PRESENTATION: The patient is a 22
      year old male who presented with headache, repeated vomiting and papilledema.He
      was a bodybuilder doing exercise since 5 years ago, who had used nandrolone
      decaonoate 25 milligrams intramuscularly during the previous 5 months. Brain MRI
      and MRV showed superior sagital and transverse sinus thrombosis and extensive
      investigations did not reveal any known cause. CONCLUSIONS: We suggested that
      androgen was the predisposing factor in our patient. Androgens may increase
      coagulation factors or platelet activity and cause arterial or venous thrombosis.
      As athletes may hide using androgens it should be considered as a predisposing
      factor for thrombotic events in such patients.

PMID- 15579202
TI  - DNA vaccines: designing strategies against parasitic infections.
AB  - The complexity of parasitic infections requires novel approaches to vaccine
      design. The versatility of DNA vaccination provides new perspectives. This review
      discusses the use of prime-boost immunizations, genetic adjuvants, multivalent
      vaccines and codon optimization for optimal DNA vaccine design against parasites.

PMID- 15579203
TI  - Multiple synaptic and membrane sites of anesthetic action in the CA1 region of
      rat hippocampal slices.
AB  - BACKGROUND: Anesthesia is produced by a depression of central nervous system
      function, however, the sites and mechanisms of action underlying this depression
      remain poorly defined. The present study compared and contrasted effects produced
      by five general anesthetics on synaptic circuitry in the CA1 region of
      hippocampal slices. RESULTS: At clinically relevant and equi-effective
      concentrations, presynaptic and postsynaptic anesthetic actions were evident at
      glutamate-mediated excitatory synapses and at GABA-mediated inhibitory synapses.
      In addition, depressant effects on membrane excitability were observed for CA1
      neuron discharge in response to direct current depolarization. Combined actions
      at several of these sites contributed to CA1 circuit depression, but the relative
      degree of effect at each site was different for each anesthetic studied. For
      example, most of propofol's depressant effect (> 70 %) was reversed with a GABA
      antagonist, but only a minor portion of isoflurane's depression was reversed (<
      20 %). Differences were also apparent on glutamate synapses-pentobarbital
      depressed transmission by > 50 %, but thiopental by only < 25 %. CONCLUSIONS:
      These results, in as much as they may be relevant to anesthesia, indicate that
      general anesthetics act at several discrete sites, supporting a multi-site, agent
      specific theory for anesthetic actions. No single effect site (e.g. GABA
      synapses) or mechanism of action (e.g. depressed membrane excitability) could
      account for all of the effects produced for any anesthetic studied.

PMID- 15579204
TI  - Effects of the group I metabotropic glutamate receptor agonist, DHPG, and
      injection stress on striatal cell signaling in food-restricted and ad libitum fed
      rats.
AB  - BACKGROUND: Chronic food restriction augments the rewarding effect of centrally
      administered psychostimulant drugs and this effect may involve a previously
      documented upregulation of D-1 dopamine receptor-mediated MAP kinase signaling in
      nucleus accumbens (NAc) and caudate-putamen (CPu). Psychostimulants are known to
      induce striatal glutamate release, and group I metabotropic glutamate receptors
      (mGluR) have been implicated in the cellular and behavioral responses to
      amphetamine. The purpose of the present study was to evaluate whether chronic
      food restriction increases striatal MAP kinase signaling in response to the group
      I mGluR agonist, DHPG. RESULTS: Western immunoblotting was used to demonstrate
      that intracerebroventricular (i.c.v.) injection of DHPG (500 nmol) produces
      greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted as
      compared to ad libitum fed rats. Fos-immunostaining induced by DHPG was also
      stronger in CPu and NAc core of food-restricted relative to ad libitum fed rats.
      However, i.c.v. injection of saline-vehicle produced greater activation of ERK1/2
      and CREB in CPu and NAc of food-restricted relative to ad libitum fed rats, and
      this difference was not seen when subjects received no i.c.v. injection prior to
      sacrifice. In addition, although DHPG activated Akt, there was no difference in
      Akt activation between feeding groups. To probe whether the augmented ERK1/2 and
      CREB activation in vehicle-injected food-restricted rats are mediated by one or
      more GluR types, effects of an NMDA antagonist (MK-801, 100 nmol), AMPA
      antagonist (DNQX, 10 nmol), and group I mGluR antagonist (AIDA, 100 nmol) were
      compared to saline-vehicle. Antagonist injections did not diminish activation of
      ERK1/2 or CREB. CONCLUSIONS: These results indicate that a group I mGluR agonist
      induces phosphorylation of Akt, ERK1/2 and CREB in both CPu and NAc. However,
      group I mGluR-mediated signaling may not be upregulated in food-restricted rats.
      Rather, a physiological response to "i.c.v. injection stress" is augmented by
      food restriction and appears to summate with effects of the group I mGluR agonist
      in activating ERK1/2 and CREB. While the augmented cellular response of food
      restricted rats to i.c.v. injection treatment represents additional evidence of
      enhanced CNS responsiveness in these subjects, the functional significance and
      underlying mechanism(s) of this effect remain to be elucidated.

PMID- 15579205
TI  - Mapping and mutation of the conserved DNA polymerase interaction motif (DPIM)
      located in the C-terminal domain of fission yeast DNA polymerase delta subunit
      Cdc27.
AB  - BACKGROUND: DNA polymerases alpha and delta play essential roles in the
      replication of chromosomal DNA in eukaryotic cells. DNA polymerase alpha (Pol
      alpha)-primase is required to prime synthesis of the leading strand and each
      Okazaki fragment on the lagging strand, whereas DNA polymerase delta (Pol delta)
      is required for the elongation stages of replication, a function it appears
      capable of performing on both leading and lagging strands, at least in the
      absence of DNA polymerase epsilon (Pol epsilon). RESULTS: Here it is shown that
      the catalytic subunit of Pol alpha, Pol1, interacts with Cdc27, one of three non
      catalytic subunits of fission yeast Pol delta, both in vivo and in vitro. Pol1
      interacts with the C-terminal domain of Cdc27, at a site distinct from the
      previously identified binding sites for Cdc1 and PCNA. Comparative protein
      sequence analysis identifies a protein sequence motif, called the DNA polymerase
      interaction motif (DPIM), in Cdc27 orthologues from a wide variety of eukaryotic
      species, including mammals. Mutational analysis shows that the DPIM in fission
      yeast Cdc27 is not required for effective DNA replication, repair or checkpoint
      function. CONCLUSIONS: A short protein sequence motif (DPIM) has been identified
      as mediating Pol alpha-Pol delta interactions in fission yeast. Despite being
      conserved across species, mutational analysis indicates the DPIM does not play an
      essential role in vivo, suggesting that interaction between the two polymerases
      is also non-essential.

PMID- 15579206
TI  - Heritability of Stroop and flanker performance in 12-year old children.
AB  - BACKGROUND: There is great interest in appropriate phenotypes that serve as
      indicator of genetically transmitted frontal (dys)function, such as ADHD. Here we
      investigate the ability to deal with response conflict, and we ask to what extent
      performance variation on response interference tasks is caused by genetic
      variation. We tested a large sample of 12-year old monozygotic and dizygotic
      twins on two well-known and closely related response interference tasks; the
      color Stroop task and the Eriksen flanker task. Using structural equation
      modelling we assessed the heritability of several performance indices derived
      from those tasks. RESULTS: In the Stroop task we found high heritabilities of
      overall reaction time and - more important - Stroop interference (h2 = nearly 50
      %). In contrast, we found little evidence of heritability on flanker performance.
      For both tasks no effects of sex on performance variation were found.
      CONCLUSIONS: These results suggest that normal variation in Stroop performance is
      influenced by underlying genetic variation. Given that Stroop performance is
      often hampered not only in people suffering from frontal dysfunction, but also in
      their unaffected relatives, we conclude that this variable may constitute a
      suitable endophenotype for future genetic studies. We discuss several reasons for
      the absence of genetic effects on the flanker task.

PMID- 15579207
TI  - Lower rate of genomic variation identified in the trans-membrane domain of
      monoamine sub-class of Human G-Protein Coupled Receptors: the Human GPCR-DB
      Database.
AB  - BACKGROUND: We have surveyed, compiled and annotated nucleotide variations in 338
      human 7-transmembrane receptors (G-protein coupled receptors). In a sample of 32
      chromosomes from a Nordic population, we attempted to determine the allele
      frequencies of 80 non-synonymous SNPs, and found 20 novel polymorphic markers.
      GPCR receptors of physiological and clinical importance were prioritized for
      statistical analysis. Natural variation and rare mutation information were merged
      and presented online in the Human GPCR-DB database http://cyrix.cgb.ki.se.
      RESULTS: The average number of SNPs per 1000 bases of exonic sequence was found
      to be twice the average number of SNPs per Kilobase of intronic regions (2.2
      versus 1.0). Of the 338 genes, 111 were single exon genes, that is, were
      intronless. The average number of exonic-SNPs per single-exon gene was 3.5 (n =
      395) while that for multi-exon genes was 0.8 (n = 1176). The average number of
      variations within the different protein domain (N-terminus, internal- and
      external-loops, trans-membrane region, C-terminus) indicates a lower rate of
      variation in the trans-membrane region of Monoamine GPCRs, as compared to
      Chemokine- and Peptide-receptor sub-classes of GPCRs. CONCLUSIONS: Single-exon
      GPCRs on average have approximately three times the number of SNPs as compared to
      GPCRs with introns. Among various functional classes of GPCRs, Monoamine GPRCs
      have lower number of natural variations within the trans-membrane domain
      indicating evolutionary selection against non-synonymous changes within the
      membrane-localizing domain of this sub-class of GPCRs.

PMID- 15579208
TI  - Evaluation of the clinical value of bone metabolic parameters for the screening
      of osseous metastases compared to bone scintigraphy.
AB  - BACKGROUND: Bone metastases are common in many types of cancer. As screening
      methods different imaging modalities are available. A new approach for the
      screening of osseous metastases represents the measurement of bone metabolic
      markers. Therefore aim of this study was to evaluate the usefulness of the
      determination of bone metabolic markers aminoterminal propeptide of type I
      procollagen (PINP, osteoblastic activity) and the carboxyterminal pyridinoline
      cross-linked telopeptide of type I collagen (ICTP, osteoclastic activity) for the
      detection of bone metastases associated with other malignancies. METHODS: 88
      patients aged 21 - 82 years with malignant tumors were prospectively studied. The
      serum concentrations of PINP and ICTP were measured and compared to the results
      of bone scintigraphy, radiological bone series, CT, MRI and clinical follow-up.
      RESULTS: Osseous metastases were found in 21 patients. 19 of them were correctly
      identified by bone scintigraphy (sensitivity: 90%). For bone metabolic markers
      results were as follows: ICTP sensitivity: 71%, specificity: 42%; PINP
      sensitivity: 24%, specificity: 96%. CONCLUSIONS: As markers of bone metabolism
      PINP and ICTP showed low sensitivity and/or specificity for the detection of
      osseous metastases. The presented markers did not seem to be sufficient enough to
      identify patients with bone metastases or to replace established screening
      methods.

PMID- 15579209
TI  - The value of the qualitative method for adaptation of a disease-specific quality
      of life assessment instrument: the case of the Rheumatoid Arthritis Quality of
      Life Scale (RAQoL) in Estonia.
AB  - BACKGROUND: Due to differences in current socio-economical situation and
      historically shaped values, different societies have their own concepts of high
      quality life. This diversity of concepts interferes with quality of life (Qol)
      research in health sciences. Before deciding to apply a Qol assessment tool
      designed in and for another society, a researcher should answer the question: how
      will this instrument work under the specific circumstances of my research. Our
      study represents an example of the utilization of qualitative research methods to
      investigate the appropriateness of the Rheumatoid Arthritis Quality of Life Scale
      (RAQol) for the assessment of Qol in Estonian patients. METHODS: Semi-structured
      interviews were conducted with the rheumatoid arthritis (RA) patients of Tartu
      University Hospital and these were analyzed using the principles of the grounded
      theory. RESULTS: We described the significance of the questionnaire's items for
      our patients and also identified topics that were important for the Qol of
      Estonian RA patients, but that were not assessed by the RAQol. We concluded that
      the RAQol can be successfully adapted for Estonia; the aspects of Qol not
      captured by the questionnaire but revealed during our study should be taken into
      account in future research. CONCLUSIONS: Our results show that qualitative
      research can successfully be used for pre-adaptation assessment of a Qol
      instrument's appropriateness.

PMID- 15579210
TI  - Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II.
AB  - BACKGROUND: Down-regulation of plasma membrane receptors via the endocytic
      pathway involves their monoubiquitylation, transport to endosomal membranes and
      eventual sorting into multi vesicular bodies (MVB) destined for lysosomal
      degradation. Successive assemblies of Endosomal Sorting Complexes Required for
      Transport (ESCRT-I, -II and III) largely mediate sorting of plasma membrane
      receptors at endosomal membranes, the formation of multivesicular bodies and
      their release into the endosomal lumen. In addition, the human ESCRT-II has been
      shown to form a complex with RNA polymerase II elongation factor ELL in order to
      exert transcriptional control activity. RESULTS: Here we report the crystal
      structure of Vps25 at 3.1 A resolution. Vps25 crystallizes in a dimeric form and
      each monomer is composed of two winged helix domains arranged in tandem.
      Structural comparisons detect no conformational changes between unliganded Vps25
      and Vps25 within the ESCRT-II complex composed of two Vps25 copies and one copy
      each of Vps22 and Vps36 12. CONCLUSIONS: Our structural analyses present a
      framework for studying Vps25 interactions with ESCRT-I and ESCRT-III partners.
      Winged helix domain containing proteins have been implicated in nucleic acid
      binding and it remains to be determined whether Vps25 has a similar activity
      which might play a role in the proposed transcriptional control exerted by Vps25
      and/or the whole ESCRT-II complex.

PMID- 15579211
TI  - A sugar beet chlorophyll a/b binding protein promoter void of G-box like elements
      confers strong and leaf specific reporter gene expression in transgenic sugar
      beet.
AB  - BACKGROUND: Modification of leaf traits in sugar beet requires a strong leaf
      specific promoter. With such a promoter, expression in taproots can be avoided
      which may otherwise take away available energy resources for sugar accumulation.
      RESULTS: Suppression Subtractive Hybridization (SSH) was utilized to generate an
      enriched and equalized cDNA library for leaf expressed genes from sugar beet.
      Fourteen cDNA fragments corresponding to thirteen different genes were isolated.
      Northern blot analysis indicates the desired tissue specificity of these genes.
      The promoters for two chlorophyll a/b binding protein genes (Bvcab11 and Bvcab12)
      were isolated, linked to reporter genes, and transformed into sugar beet using
      promoter reporter gene fusions. Transient and transgenic analysis indicate that
      both promoters direct leaf specific gene expression. A bioinformatic analysis
      revealed that the Bvcab11 promoter is void of G-box like regulatory elements with
      a palindromic ACGT core sequence. The data indicate that the presence of a G-box
      element is not a prerequisite for leaf specific and light induced gene expression
      in sugar beet. CONCLUSIONS: This work shows that SSH can be successfully employed
      for the identification and subsequent isolation of tissue specific sugar beet
      promoters. These promoters are shown to drive strong leaf specific gene
      expression in transgenic sugar beet. The application of these promoters for
      expressing resistance improving genes against foliar diseases is discussed.

PMID- 15579212
TI  - Chloride equilibrium potential in salamander cones.
AB  - BACKGROUND: GABAergic inhibition and effects of intracellular chloride ions on
      calcium channel activity have been proposed to regulate neurotransmission from
      photoreceptors. To assess the impact of these and other chloride-dependent
      mechanisms on release from cones, the chloride equilibrium potential (ECl) was
      determined in red-sensitive, large single cones from the tiger salamander retinal
      slice. RESULTS: Whole cell recordings were done using gramicidin perforated patch
      techniques to maintain endogenous Cl- levels. Membrane potentials were corrected
      for liquid junction potentials. Cone resting potentials were found to average -46
      mV. To measure ECl, we applied long depolarizing steps to activate the calcium
      activated chloride current (ICl(Ca)) and then determined the reversal potential
      for the current component that was inhibited by the Cl- channel blocker, niflumic
      acid. With this method, ECl was found to average -46 mV. In a complementary
      approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by
      depolarization with elevated concentrations of K+. The membrane potentials
      produced by the various high K+ solutions were measured in separate current clamp
      experiments. Consistent with electrophysiological experiments, MEQ fluorescence
      measurements indicated that ECl was below -36 mV. CONCLUSIONS: The results of
      this study indicate that ECl is close to the dark resting potential. This will
      minimize the impact of chloride-dependent presynaptic mechanisms in cone
      terminals involving GABAa receptors, glutamate transporters and ICl(Ca).

PMID- 15579213
TI  - P80, the HinT interacting membrane protein, is a secreted antigen of Mycoplasma
      hominis.
AB  - BACKGROUND: Mycoplasmas are cell wall-less bacteria which encode a minimal set of
      proteins. In Mycoplasma hominis, the genes encoding the surface-localized
      membrane complex P60/P80 are in an operon with a gene encoding a cytoplasmic,
      nucleotide-binding protein with a characteristic Histidine triad motif (HinT).
      HinT is found in both procaryotes and eukaryotes and known to hydrolyze adenosine
      nucleotides in eukaryotes. Immuno-precipitation and BIACore analysis revealed an
      interaction between HinT and the P80 domain of the membrane complex. As the
      membrane anchored P80 carries an N-terminal uncleaved signal peptide we have
      proposed that the N-terminus extends into the cytoplasm and interacts with the
      cytosolic HinT. RESULTS: Further characterization of P80 suggested that the 4.7
      kDa signal peptide is protected from cleavage only in the membrane bound form. We
      found several proteins were released into the supernatant of a logarithmic phase
      mycoplasma culture, including P80, which was reduced in size by 10 kDa. Western
      blot analysis of recombinant P80 mutants expressed in E. coli and differing in
      the N-terminal region revealed that mutation of the +1 position of the mature
      protein (Asn to Pro) which is important for signal peptidase I recognition
      resulted in reduced P80 secretion. All other P80 variants were released into the
      supernatant, in general as a 74 kDa protein encompassing the helical part of P80.
      Incubation of M. hominis cells in phosphate buffered saline supplemented with
      divalent cations revealed that the release of mycoplasma proteins into the
      supernatant was inhibited by high concentrations of calciumions. CONCLUSIONS: Our
      model for secretion of the P80 protein of M. hominis implies a two-step process.
      In general the P80 protein is transported across the membrane and remains
      complexed to P60, surface-exposed and membrane anchored via the uncleaved signal
      sequence. Loss of the 4.7 kDa signal peptide seems to be a pre-requisite for P80
      secretion, which is followed by a proteolytic process leading to a helical 74 kDa
      product. We propose that this novel form of two-step secretion is one of the
      solutions to a life with a reduced gene set.

PMID- 15579214
TI  - Participation of African social scientists in malaria control: identifying
      enabling and constraining factors.
AB  - OBJECTIVE: To examine the enabling and constraining factors that influence
      African social scientists involvement in malaria control. METHODS: Convenience
      and snowball sampling was used to identify participants. Data collection was
      conducted in two phases: a mailed survey was followed by in-depth phone
      interviews with selected individuals chosen from the survey. FINDINGS: Most
      participants did not necessarily seek malaria as a career path. Having a mentor
      who provided research and training opportunities, and developing strong technical
      skills in malaria control and grant or proposal writing facilitated career
      opportunities in malaria. A paucity of jobs and funding and inadequate technical
      skills in malaria limited the type and number of opportunities available to
      social scientists in malaria control. CONCLUSION: Understanding the factors that
      influence job satisfaction, recruitment and retention in malaria control is
      necessary for better integration of social scientists into malaria control.
      However, given the wide array of skills that social scientists have and the
      variety of deadly diseases competing for attention in Sub Saharan Africa, it
      might be more cost effective to employ social scientists to work broadly on
      issues common to communicable diseases in general rather than solely on malaria.

PMID- 15579215
TI  - Gender: a major determinant of brain response to nicotine.
AB  - Biological factors responsible for nicotine initiation and dependence are largely
      unknown. Men and women smoke differently, and may smoke for different reasons.
      Brain metabolic response to nicotine may explain gender differences in nicotine
      use. We used FDG-PET to measure brain metabolic response on placebo and following
      nicotine administered by patch in 42 females and 77 males (smokers and non
      smokers) while performing a Continuous Performance Task (CPT) or the Bushman
      Competition and Retaliation Task (CRT). Nicotine administration affected brain
      metabolism much differently in males and females, and these differences were
      dependent on task and smoking history. In the placebo condition female smokers
      performing the CPT and female non-smokers performing the CRT consistently had
      higher brain metabolism than males, especially in the entire prefrontal system
      and the mid and anterior temporal lobe, language cortices, and related
      subcortical systems. The overall effect of nicotine was to decrease these gender
      differences in brain metabolism.

PMID- 15579216
TI  - How much feedback from visual cortex to lateral geniculate nucleus in cat: a
      perspective.
AB  - Corticothalamic feedback is believed to play an important role in selectively
      regulating the flow of sensory information from thalamus to cortex. But despite
      its importance, the size and nature of corticothalamic pathway connectivity is
      not fully understood. In light of recent empirical data, the aim of this paper
      was to quantify the contribution of area 17 axon connectivity to the synaptic
      organization of A-laminae in dorsal lateral geniculate nucleus (dLGN) in cat, the
      best studied corticothalamic pathway. Numerical constraints indicate that most
      corticogeniculate synapses are not formed with inhibitory interneurons. However,
      the main finding is that there was an order of magnitude difference between
      estimates of the mean number of cortical synapses per A-laminae neuron based on
      individual corticogeniculate axon data (12,000-16,000 cortical synapses per cell)
      than that previously derived from partial reconstructions of the synaptic input
      to two physiologically identified relay cells (1200-1500 cortical synapses per
      cell). In an attempt to reconcile these different estimates, parameter variation
      and comparative analyses suggest that previous work may have overestimated the
      density of corticogeniculate efferent neurons and underestimated the total number
      of synapses per geniculate neuron. But as this analysis did not include area 18
      corticogeniculate axons innervating A-laminae, the discrepancy between different
      estimates may be greater and require further explanation. Thus, the analysis
      presented here suggests geniculate neurons receive on average a greater number of
      cortical synapses per cell but from far fewer corticogeniculate axons than
      previously thought.

PMID- 15579217
TI  - Cobalt ions inhibit negative feedback in the outer retina by blocking
      hemichannels on horizontal cells.
AB  - In goldfish, negative feedback from horizontal cells to cones shifts the
      activation function of the Ca2+ current of the cones to more negative potentials.
      This shift increases the amount of Ca2+ flowing into the cones, resulting in an
      increase in glutamate release. The increased glutamate release forms the basis of
      the feedback-mediated responses in second-order neurons, such as the surround
      induced responses of bipolar cells and the spectral coding of horizontal cells.
      Low concentrations of Co2+ block these feedback-mediated responses in turtle
      retina. The mechanism by which this is accomplished is unknown. We studied the
      effects of Co2+ on the cone/horizontal network of goldfish retina and found that
      Co2+ greatly reduced the feedback-mediated responses in both cones and horizontal
      cells in a GABA-independent way. The reduction of the feedback-mediated responses
      is accompanied by a small shift of the Ca2+ current of the cones to positive
      potentials. We have previously shown that hemichannels on the tips of the
      horizontal cell dendrites are involved in the modulation of the Ca2+ current in
      cones. Both the absence of this Co2+-induced shift of the Ca2+ current in the
      absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to
      low concentrations of Co2+ are consistent with a role for hemichannels in
      negative feedback from horizontal cells to cones.

PMID- 15579218
TI  - Visual sensitivity across the menstrual cycle.
AB  - This study was designed to evaluate the hypothesis that hormonal change can
      affect lower level light-adaptation processes, which are likely to be retinally
      based. Foveal visual sensitivities were measured across several menstrual cycles
      of four women not using hormonally acting medication and across several menstrual
      cycles of three women using a triphasic oral contraceptive. One woman, diagnosed
      with premenstrual syndrome (PMS), was a subject for both groups. Sensitivities
      were measured for a series of test wavelengths for 580-nm backgrounds of 2.0 and
      4.0 log td. Of the six individuals tested, one had clear evidence of visual
      adaptation changes occurring in phase with the menstrual cycle. Prior to using
      the oral contraceptive, this individual (the PMS subject) experienced changes of
      short-wavelength-sensitive (SWS)-cone-mediated sensitivities of up to about 1.4
      log unit on the 4.0 log td background. Her SWS-cone-mediated sensitivities tended
      to be highest near ovulation and lowest premenstrually. Threshold-versus
      illuminance (TVI) curves confirmed that the rate of sensitivity decrease with
      increasing background illuminance (i.e. the TVI slope) was greater
      premenstrually. The degree of background-induced desensitization within her
      middle-wavelength-sensitive (MWS)/long-wavelength-sensitive (LWS) cone pathways
      also appeared to vary cyclically, but the magnitude of the variation was smaller
      and the time course appeared to be different. When this subject began oral
      contraceptive use, the patterns of sensitivity change were all altered. None of
      the other five subjects experienced changes of SWS-cone-mediated vision that were
      cyclic and significantly adaptation-state dependent. However, there was evidence
      for a limited degree of cyclic adaptation change within the MWS/LWS cone pathways
      of at least one additional subject. We conclude that hormonal change can--for
      some unknown proportion of women--be linked to alterations of retinal function.
      However, the alterations are not the same for all visual pathways, and there are
      pronounced individual differences. The data also demonstrate that individuals'
      visual adaptation capabilities can vary substantially over periods of weeks.

PMID- 15579219
TI  - Origins of the electroretinogram oscillatory potentials in the rabbit retina.
AB  - The electroretinogram (ERG) oscillatory potential (OP) is a high-frequency, low
      amplitude potential that is superimposed on the rising phase of the b-wave. It
      provides noninvasive evaluation of inner retina function in vivo and is a useful
      tool in basic research as well as in the clinic. While the OP is widely believed
      to be generated mainly by activity of the inner retina, the exact underlying
      neural mechanisms are not well understood. We have investigated the retinal
      mechanisms that underlie OP generation in Dutch-belted rabbits. The OP was
      isolated by band-filtering (100-1000 Hz) ERG signals. We used pharmacological
      agents that block specific transmitter receptors or voltage-gated channels in
      order to examine contributions of various retinal mechanisms to OP generation.
      Our results show that the OP elicited by a bright brief flash can be classified
      into early, intermediate, and late subgroups that are likely generated mainly by
      photoreceptors, action-potential-independent, and action-potential-dependent
      mechanisms in the ON pathway of the inner retina, respectively. ON bipolar cells
      themselves make only a small direct contribution to OP generation, as do
      horizontal cells and neurons in the OFF pathway.

PMID- 15579220
TI  - N-type and L-type calcium channels mediate glycinergic synaptic inputs to retinal
      ganglion cells of tiger salamanders.
AB  - Synaptically localized calcium channels shape the timecourse of synaptic release,
      are a prominent site for neuromodulation, and have been implicated in genetic
      disease. In retina, it is well established that L-type calcium channels play a
      major role in mediating release of glutamate from the photoreceptors and bipolar
      cells. However, little is known about which calcium channels are coupled to
      synaptic exocytosis of glycine, which is primarily released by amacrine cells. A
      recent report indicates that glycine release from spiking AII amacrine cells
      relies exclusively upon L-type calcium channels. To identify calcium channel
      types controlling neurotransmitter release from the population of glycinergic
      neurons that drive retinal ganglion cells, we recorded electrical and potassium
      evoked inhibitory synaptic currents (IPSCs) from these postsynaptic neurons in
      retinal slices from tiger salamanders. The L-channel antagonist nifedipine
      strongly inhibited release and FPL64176, an L-channel agonist, greatly enhanced
      it, indicating a significant role for L-channels. omega-Conotoxin MVIIC, an N/P/Q
      channel antagonist, strongly inhibited release, indicating an important role for
      non-L channels. While the P/Q-channel blocker omega-Aga IVA produced only small
      effects, the N-channel blocker omega-conotoxin GVIA strongly inhibited release.
      Hence, N-type and L-type calcium channels appear to play major roles, overall, in
      mediating synaptic release of glycine onto retinal ganglion cells.

PMID- 15579221
TI  - Differential cellular and subcellular distribution of glutamate transporters in
      the cat retina.
AB  - Retrieval of glutamate from extracellular sites in the retina involves at least
      five excitatory amino acid transporters. Immunocytochemical analysis of the cat
      retina indicates that each of these transporters exhibits a selective
      distribution which may reflect its specific function. The uptake of glutamate
      into Muller cells or astrocytes appears to depend upon GLAST and EAAT4,
      respectively. Staining for EAAT4 was also seen in the pigment epithelium. The
      remaining transporters are neuronal with GLT-1alpha localized to a number of cone
      bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and
      several populations of bipolar cells. The EAAC1 transporter was found in
      horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon
      terminals of both rod and cone photoreceptors as well as in numerous amacrine and
      ganglion cells. Although some of the glutamate transporter molecules are
      positioned for presynaptic or postsynaptic uptake at glutamatergic synapses,
      others with localizations more distant from such contacts may serve in modulatory
      roles or provide protection against excitoxic or oxidative damage.

PMID- 15579222
TI  - The computational basis of an identified neuronal circuit for elementary motion
      detection in dipterous insects.
AB  - Based on comparative anatomical studies and electrophysiological experiments, we
      have identified a conserved subset of neurons in the lamina, medulla, and lobula
      of dipterous insects that are involved in retinotopic visual motion direction
      selectivity. Working from the photoreceptors inward, this neuronal subset
      includes lamina amacrine (alpha) cells, lamina monopolar (L2) cells, the basket T
      cell (T1 or beta), the transmedullary cell Tm1, and the T5 bushy T-cell. Two GABA
      immunoreactive neurons, the transmedullary cell Tm9 and a local interneuron at
      the level of T5 dendrites, are also implicated in the motion computation. We
      suggest that these neurons comprise the small-field elementary motion detector
      circuits the outputs of which are integrated by wide-field lobula plate
      tangential cells. We show that a computational model based on the available data
      about these neurons is consistent with existing models of biological elementary
      motion detection, and present a comparable version of the Hassenstein-Reichardt
      (HR) correlation model. Further, by using the model to synthesize a generic
      tangential cell, we show that it can account for the responses of lobula plate
      tangential cells to a wide range of transient stimuli, including responses which
      cannot be predicted using the HR model. This computational model of elementary
      motion detection is the first which derives specifically from the functional
      organization of a subset of retinotopic neurons supplying the lobula plate. A key
      prediction of this model is that elementary motion detector circuits respond
      quite differently to small-field transient stimulation than do spatially
      integrated motion processing neurons as observed in the lobula plate. In
      addition, this model suggests that the retinotopic motion information provided to
      wide-field motion-sensitive cells in the lobula is derived from a less refined
      stage of processing than motion inputs to the lobula plate.

PMID- 15579223
TI  - Light-induced Ca2+ release in the visible cones of the zebrafish.
AB  - We used suction-pipette recording and fluo-4 fluorescence to study light-induced
      Ca2+ release from the visible double cones of zebrafish. In Ringer, light
      produces a slow decrease in fluorescence which can be fitted by the sum of two
      decaying exponentials with time constants of 0.5 and 3.8 s. In 0Ca2+-0Na+
      solution, for which fluxes of Ca2+ across the outer segment plasma membrane are
      greatly reduced, light produces a slow increase in fluorescence. Both the
      decrease and increase are delayed after incorporation of the Ca2+ chelator BAPTA,
      indicating that both are produced by a change in Ca2+. If the Ca2+ pool is first
      released by bright light in 0Ca2+-0Na+ solution and the cone returned to Ringer,
      the time course of Ca2+ decline is much faster than in Ringer without previous
      light exposure. This indicates that the time constants of 0.5 and 3.8 s actually
      reflect a sum of Na+/Ca2+-K+ exchange and light-induced release of Ca2+. The Ca2+
      released by light appears to come from at least two sites, the first comprising
      66% of the total pool and half-released by bleaching 4.8% of the pigment. Release
      of the remaining Ca2+ from the second site requires the bleaching of nearly all
      of the pigment. If, after release, the cone is maintained in darkness, a
      substantial fraction of the Ca2+ returns to the release pool even in the absence
      of pigment regeneration. The light-induced release of Ca2+ can produce a
      modulation of the dark current as large as 0.75 pA independently of the normal
      transduction cascade, though the rise time of the current is considerably slower
      than the normal light response. These experiments show that Ca2+ can be released
      within the cone outer segment by light intensities within the physiological range
      of photopic vision. The role this Ca2+ release plays remains unresolved.

PMID- 15579224
TI  - Direction selectivity in a model of the starburst amacrine cell.
AB  - The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to
      provide the directional inhibitory input recorded in On-Off direction-selective
      ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not
      shown robust direction selectivity (DS), the dendritic tips of these cells
      display direction-selective calcium signals, even when gamma-aminobutyric acid
      (GABAa,c) channels are blocked, implying that inhibition is not necessary to
      generate DS. This suggested that the distinctive morphology of the SBAC could
      generate a DS signal at the dendritic tips, where most of its synaptic output is
      located. To explore this possibility, we constructed a compartmental model
      incorporating realistic morphological structure, passive membrane properties, and
      excitatory inputs. We found robust DS at the dendritic tips but not at the soma.
      Two-spot apparent motion and annulus radial motion produced weak DS, but thin
      bars produced robust DS. For these stimuli, DS was caused by the interaction of a
      local synaptic input signal with a temporally delayed "global" signal, that is,
      an excitatory postsynaptic potential (EPSP) that spread from the activated inputs
      into the soma and throughout the dendritic tree. In the preferred direction the
      signals in the dendritic tips coincided, allowing summation, whereas in the null
      direction the local signal preceded the global signal, preventing summation. Sine
      wave grating stimuli produced the greatest amount of DS, especially at high
      velocities and low spatial frequencies. The sine-wave DS responses could be
      accounted for by a simple mathematical model, which summed phase-shifted signals
      from soma and dendritic tip. By testing different artificial morphologies, we
      discovered DS was relatively independent of the morphological details, but
      depended on having a sufficient number of inputs at the distal tips and a limited
      electrotonic isolation. Adding voltage-gated calcium channels to the model showed
      that their threshold effect can amplify DS in the intracellular calcium signal.

PMID- 15579225
TI  - Spatial, temporal, and intensive determinants of dopamine release in the chick
      retina.
AB  - The retinal dopaminergic system is a global regulator of retinal function. Apart
      from the fact that the rates of dopamine synthesis and release are increased by
      increasing illumination, the visual image parameters that influence dopaminergic
      function are mostly unknown. Roles for spatial and temporal frequency and image
      contrast are suggested by the effects of form-deprivation with a diffusing
      goggle. Form-deprivation reduces the rates of dopamine synthesis and release, and
      induces myopia, which is prevented by dopamine agonists. Our purpose here was to
      identify visual stimulus parameters that activate dopaminergic amacrine cells and
      elicit dopamine release. White Leghorn cockerels 4-7 days old were exposed to 2 h
      of form-deprivation, reduced light intensity, or stimuli of varied temporal or
      spatial frequency. Activation of dopaminergic neurons, labeled for tyrosine
      hydroxylase (TH), was assessed with immunocytochemistry for c-Fos, and dopamine
      release was measured by HPLC analysis of dopamine metabolite accumulation in the
      vitreous body. Form-deprivation did not reduce TH+ cell activation or vitreal
      dopamine metabolite accumulation any more than did neutral-density filters of
      approximately equal transmittance. TH+ cell activation and vitreal metabolite
      accumulation were not affected significantly by exposure to 2, 5, 10, 15, or 20
      Hz stroboscopic stimulation on a dark background, or by sine-wave gratings of
      0.089, 0.44, 0.89, 1.04, or 3.13 cycles/deg compared to a uniform gray target of
      equal mean luminance. These data indicate that the retinal dopaminergic system
      does not respond readily to short-term changes in visual stimulus parameters,
      other than light intensity, under the conditions of these experiments.

PMID- 15579226
TI  - Retinal glucose metabolism in mice lacking the L-glutamate/aspartate transporter.
AB  - The conventional view that glucose is the substrate for neuronal energy
      metabolism has been recently challenged by the "lactate shuttle" hypothesis in
      which glutamate cycling in glial cells drives all neuronal glucose metabolism.
      According to this view, glutamate released by activated retinal neurons is
      transported into Muller (glial) cells where it triggers glycolysis. The lactate
      released by Muller cells serves as the energy substrate for neuronal metabolism.
      Because the L-Glutamate/aspartate transporter (GLAST) is the predominant, Na+
      dependent, glutamate transporter expressed by Muller cells, we have used GLAST
      knockout (GLAST -/-) mice to examine the relationship between lactate release and
      GLAST activity in the retina. We found that glucose uptake and lactate production
      by the GLAST -/- mouse retina was similar to that observed in the wild type mouse
      retina. Furthermore, addition of 1 mM glutamate and NH4Cl to the incubation
      medium did not further stimulate glucose uptake in either case. When lactate
      release was measured in the presence of the lactate uptake inhibitor, alpha-cyano
      4-hydroxycinnamate, there was no significant change in the amount of lactate
      released by retinas from GLAST -/- mice compared to the wild type. Finally,
      lactate release was similar under both dark and light conditions. These results
      show that lactate production and release is not altered in retinas of GLAST -/-
      mice, which suggests that metabolic coupling between photoreceptors and Muller
      cells is not mediated by the glial glutamate transporter, GLAST.

PMID- 15579227
TI  - Characterization of inhibitory postsynaptic currents in rod bipolar cells of the
      mouse retina.
AB  - The synaptic terminals of mammalian rod bipolar cells are the targets of multiple
      presynaptic inhibitory inputs arriving from glycinergic and GABAergic amacrine
      cells. To investigate the contribution of these different inhibitory receptor
      types, we have applied the patch-clamp technique in acutely isolated slices of
      the adult mouse retina. By using the whole-cell configuration, we measured and
      analyzed the spontaneous postsynaptic currents (PSCs) in rod bipolar cells. The
      spontaneous synaptic activity of rod bipolar cells was very low. However, when
      amacrine cells were depolarized by AMPA or kainate, the PSC frequency in rod
      bipolar cells increased significantly. These PSCs comprised several types that
      could be distinguished by pharmacological and kinetic criteria. Strychnine
      sensitive, glycinergic PSCs were characterized by a mean peak amplitude of -43.5
      pA and a weighted decay time constant (tauw) of 10.9 ms. PSCs that persisted in
      the presence of strychnine, but were completely inhibited by bicuculline, were
      mediated by GABAARs. They had a mean peak amplitude of -20.0 pA and a
      significantly faster tauw of 5.8 ms. Few PSCs remained in the presence of
      strychnine and bicuculline, suggesting that they were mediated by GABACRs. These
      PSCs were characterized by much smaller amplitudes (-6.2 pA) and a significantly
      slower decay kinetics (tauw=51.0 ms). We conclude that rod bipolar cells express
      at least three types of functionally different inhibitory receptors, namely
      GABAARs, GABACRs, and GlyRs that may ultimately regulate the Ca2+ influx into rod
      bipolar cell terminals, thereby modulating their glutamate release.

PMID- 15579228
TI  - Experience-dependent changes in NMDAR1 expression in the visual cortex of an
      animal model for amblyopia.
AB  - When normal binocular visual experience is disrupted during postnatal
      development, it affects the maturation of cortical circuits and often results in
      the development of poor visual acuity known as amblyopia. Two main factors
      contribute to the development of amblyopia: visual deprivation and reduced
      binocular competition. We investigated the affect of these two amblyogenic
      factors on the expression of the NMDAR1 subunit in the visual cortex because
      activation of the NMDA receptor is a key mechanism of developmental neural
      plasticity. We found that disruption of binocular correlations by monocular
      deprivation promoted a topographic loss of NMDAR1 expression within the cortical
      representations of the central visual field and the vertical and horizontal
      meridians. In contrast, binocular deprivation, which primarily affects visual
      deprivation, promoted an increase in NMDAR1 expression throughout the visual
      cortex. These different changes in NMDAR1 expression can be described as
      topographic and homeostatic plasticity of NMDA expression, respectively. In
      addition, the changes in NMDA expression in the visual cortex provide a greater
      understanding of the neural mechanisms that underlie the development of amblyopia
      and the potential for visual recovery.

PMID- 15579229
TI  - Growth characteristics of renal cortical tumors in patients managed by watchful
      waiting.
AB  - OBJECTIVE: To characterize tumor growth of patients managed conservatively for
      renal cell carcinoma. METHODS: Patients electing conservative management of
      radiographically determined renal cell carcinomas were referred to a surveillance
      database. Exclusion criteria consisted of locally advanced disease (>T2) and
      those with metastatic disease. Clinical follow-up included renal imaging with
      ultrasound or computed tomography at least every 6 months. RESULTS: Twenty-two
      patients were originally managed conservatively, two of whom subsequently
      underwent nephrectomy because of rapid tumor growth. Mean follow-up was 26
      months. Mean tumor volume and diameter at presentation was 62.4 cc and 4.08 cm
      respectively. Overall tumor growth was 24 cc/year by volume or .86 cm/year
      diameter. CONCLUSIONS: Given the stage migration of incidentally detected renal
      masses, the natural history of these tumors remains incomplete. Overall tumor
      growth in selected populations appear to be slow even in those diagnosed with
      larger masses. These data may be useful in counseling patients and directing
      further trials on conservative therapy for renal cell carcinoma.

PMID- 15579230
TI  - The analysis of stress-induced duplex destabilization in long genomic DNA
      sequences.
AB  - We present a method for calculating predicted locations and extents of stress
      induced DNA duplex destabilization (SIDD) as functions of base sequence and
      stress level in long DNA molecules. The base pair denaturation energies are
      assigned individually, so the influences of near neighbors, methylated bases,
      adducts, or lesions can be included. Sample calculations indicate that
      copolymeric energetics give results that are close to those derived when full
      near-neighbor energetics are used; small but potentially informative differences
      occur only in the calculated SIDD properties of moderately destabilized regions.
      The method presented here for analyzing long sequences calculates the
      destabilization properties within windows of fixed length N, with successive
      windows displaced by an offset distance d(o). The final values of the relevant
      destabilization parameters for each base pair are calculated as weighted averages
      of the values computed for each window in which that base pair appears. This
      approach implicitly assumes that the strength of the direct coupling between
      remote base pairs that is induced by the imposed stress attenuates with their
      separation distance. This strategy enables calculations of the destabilization
      properties of DNA sequences of any length, up to and including complete
      chromosomes. We illustrate its utility by calculating the destabilization
      properties of the entire E. coli genomic DNA sequence. A preliminary analysis of
      the results shows that promoters are associated with SIDD regions in a highly
      statistically significant manner, suggesting that SIDD attributes may prove
      useful in the computational prediction of promoter locations in prokaryotes.

PMID- 15579231
TI  - Cue-signal-response analysis of TNF-induced apoptosis by partial least squares
      regression of dynamic multivariate data.
AB  - Biological signaling networks process extracellular cues to control important
      cell decisions such as death-survival, growth-quiescence, and proliferation
      differentiation. After receptor activation, intracellular signaling proteins
      change in abundance, modification state, and enzymatic activity. Many of the
      proteins in signaling networks have been identified, but it is not known how
      signaling molecules work together to control cell decisions. To begin to address
      this issue, we report the use of partial least squares regression as an
      analytical method to glean signal-response relationships from heterogeneous
      multivariate signaling data collected from HT-29 human colon carcinoma cells
      stimulated to undergo programmed cell death. By partial least squares modeling,
      we relate dynamic and quantitative measurements of 20-30 intracellular signals to
      cell survival after treatment with tumor necrosis factor alpha (a death factor)
      and insulin (a survival factor). We find that partial least squares models can
      distinguish highly informative signals from redundant uninformative signals to
      generate a reduced model that retains key signaling features and signal-response
      relationships. In these models, measurements of biochemical characteristics,
      based on very different techniques (Western blots, kinase assays, etc.), are
      grouped together as covariates, showing that heterogenous data have been
      effectively fused. Importantly, informative protein predictors of cell responses
      are always multivariate, demonstrating the multicomponent nature of the decision
      process.

PMID- 15579232
TI  - A mixed polyploid model for linkage analysis in outcrossing tetraploids using a
      pseudo-test backcross design.
AB  - Based on how chromosomes pair at meiosis, the nature of polyploids can be
      described by bivalent polyploids, multivalent polyploids, and mixed polyploids.
      In bivalent polyploids, only two chromosomes pair, during which two more similar
      chromosomes have a higher pairing probability (preferential pairing) than two
      less similar chromosomes, whereas in multivalent polyploids more than two
      chromosomes pair at a time, which results in double reduction. Preferential
      chromosome pairings and double reduction affect the frequencies of gamete
      formation and, therefore, linkage analysis of polymorphic markers in bivalent and
      multivalent polyploids, respectively. For mixed polyploids, in which both
      bivalent and multivalent formations occur simultaneously, linkage analysis is
      affected by both preferential pairings and double reduction. In this study, we
      develop a hierarchical maximum likelihood model for discerning gamete genotypes
      derived from different pairing mechanisms and different formation modes. The
      first-stage model in the hierarchy is formulated to characterize the relative
      frequencies of bivalent and multivalent pairing configurations in terms of the
      preferential pairing factor. The second-stage model is derived to rule out
      identical gamete genotypes into their different formation modes with relative
      probabilities determined by the recombination fraction. The first-stage pairing
      mechanism and second-stage formation mode are integrated to provide the
      simultaneous maximum likelihood estimates of the preferential pairing factor, the
      frequency of double reduction, and the recombination fraction, by implementing
      the EM algorithm. We performed extensive simulation studies to demonstrate the
      statistical properties of our hierarchical model for linkage analysis in
      tetraploids. The implications of our model for polyploid linkage mapping are
      discussed.

PMID- 15579233
TI  - A Bayesian network classification methodology for gene expression data.
AB  - We present new techniques for the application of a Bayesian network learning
      framework to the problem of classifying gene expression data. The focus on
      classification permits us to develop techniques that address in several ways the
      complexities of learning Bayesian nets. Our classification model reduces the
      Bayesian network learning problem to the problem of learning multiple
      subnetworks, each consisting of a class label node and its set of parent genes.
      We argue that this classification model is more appropriate for the gene
      expression domain than are other structurally similar Bayesian network
      classification models, such as Naive Bayes and Tree Augmented Naive Bayes (TAN),
      because our model is consistent with prior domain experience suggesting that a
      relatively small number of genes, taken in different combinations, is required to
      predict most clinical classes of interest. Within this framework, we consider two
      different approaches to identifying parent sets which are supported by the gene
      expression observations and any other currently available evidence. One approach
      employs a simple greedy algorithm to search the universe of all genes; the second
      approach develops and applies a gene selection algorithm whose results are
      incorporated as a prior to enable an exhaustive search for parent sets over a
      restricted universe of genes. Two other significant contributions are the
      construction of classifiers from multiple, competing Bayesian network hypotheses
      and algorithmic methods for normalizing and binning gene expression data in the
      absence of prior expert knowledge. Our classifiers are developed under a cross
      validation regimen and then validated on corresponding out-of-sample test sets.
      The classifiers attain a classification rate in excess of 90% on out-of-sample
      test sets for two publicly available datasets. We present an extensive
      compilation of results reported in the literature for other classification
      methods run against these same two datasets. Our results are comparable to, or
      better than, any we have found reported for these two sets, when a train-test
      protocol as stringent as ours is followed.

PMID- 15579234
TI  - An efficient Z-score algorithm for assessing sequence alignments.
AB  - We describe an alternative method for scoring of the pairwise alignment of two
      biological sequences. Designed to overcome the bias due to the composition of the
      alignment, it measures the distance (in standard deviations) between the given
      alignment and the mean value of all other alignments that can be obtained by a
      permutation of either sequence. We demonstrate that the standard deviation can be
      calculated efficiently. By concentrating upon the ungapped case, the mean and
      standard deviation can be calculated exactly and in two steps, the first being
      O(N) time, where N is the length of the sequence, the second in a fixed number of
      calculations, i.e., in O(1) time. We argue that this statistic is a more
      consistent measure than a similarity score based upon a standard scoring matrix.
      Even in the ungapped case, the statistic proves in many cases to be more accurate
      than the commonly used (FASTA) (Pearson and Lipman, 1988) gapped Z-score in which
      the sequence is matched against a random sample of the database. We demonstrate
      the use of the POZ-score as a secondary filter which screens out several well
      known types of false positive, reducing the amount of manual screening to be done
      by the biologist.

PMID- 15579235
TI  - Comparing DNA damage-processing pathways by computer analysis of chromosome
      painting data.
AB  - Chromosome aberrations are large-scale illegitimate rearrangements of the genome.
      They are indicative of DNA damage and informative about damage processing
      pathways. Despite extensive investigations over many years, the mechanisms
      underlying aberration formation remain controversial. New experimental assays
      such as multiplex fluorescent in situ hybridyzation (mFISH) allow combinatorial
      "painting" of chromosomes and are promising for elucidating aberration formation
      mechanisms. Recently observed mFISH aberration patterns are so complex that
      computer and graph-theoretical methods are needed for their full analysis. An
      important part of the analysis is decomposing a chromosome rearrangement process
      into "cycles." A cycle of order n, characterized formally by the cyclic graph
      with 2n vertices, indicates that n chromatin breaks take part in a single
      irreducible reaction. We here describe algorithms for computing cycle structures
      from experimentally observed or computer-simulated mFISH aberration patterns. We
      show that analyzing cycles quantitatively can distinguish between different
      aberration formation mechanisms. In particular, we show that homology-based
      mechanisms do not generate the large number of complex aberrations, involving
      higher-order cycles, observed in irradiated human lymphocytes.

PMID- 15579236
TI  - Closed-loop learning control of bio-networks.
AB  - A general goal of systems biology is to acquire a detailed quantitative
      understanding of the life-sustaining interactions between genes and proteins.
      There arises an interesting question of whether these network dynamics can be
      controlled externally. In the open-loop approach to experimental biology, a
      control design would be chosen based on a desired target response and modeling
      with all the available knowledge about the system. If the system is not
      completely understood or disturbances occur, then unexpected deviations from the
      desired response can arise. A means to circumvent this difficulty is to optimize
      the controls in a closed-loop operation by modifying successive input controls
      based on the performance of previous controls. This paper presents a simulation
      of closed-loop learning control applied to biological systems in order to
      generate a desired response. The most powerful advantage of this technique is
      that the controls are deduced based on experimental results and the process can
      operate without a model for the underlying biochemical network. This feature
      eliminates the problem of faulty predictions as well as the need for a detailed
      understanding of the underlying molecular pathways, suggesting that biological
      systems can be controlled even before the post-systems biology era.

PMID- 15579237
TI  - Fast iterative gene clustering based on information theoretic criteria for
      selecting the cluster structure.
AB  - Grouping of genes into clusters according to their expression levels is important
      for deriving biological information, e.g., on gene functions based on microarray
      and other related analyses. The paper introduces the selection of the number of
      clusters based on the minimum description length (MDL) principle for the
      selection of the number of clusters in gene expression data. The main feature of
      the new method is the ability to evaluate in a fast way the number of clusters
      according to the sound MDL principle, without exhaustive evaluations over all
      possible partitions of the gene set. The estimation method can be used in
      conjunction with various clustering algorithms. A recent clustering algorithm
      using principal component analysis, the "gene shaving" (GS) procedure, can be
      modified to make use of the new MDL estimation method, replacing the Gap
      statistics originally used in GS algorithm. The resulting clustering algorithm is
      shown to perform better than GS-Gap and CEM (classification expectation
      maximization), in the simulations using artificial data. The proposed method is
      applied to B-cell differentiation data, and the resulting clusters are compared
      with those found by self-organizing maps (SOM).

PMID- 15579238
TI  - Toward the quantitative prediction of T-cell epitopes: QSAR studies on peptides
      having affinity with the class I MHC molecular HLA-A*0201.
AB  - It would be useful for vaccine development to develop a method of rapidly
      identifying peptide epitopes. In this paper, the empirical three-dimensional
      quantitative structure-affinity relationship (3D-QSAR) methods were used to study
      the relationship between the three dimensional structural parameters (the
      isotropic surface area, ISA, and the electronic charge index, ECI) of the HLA
      A*0201 binding peptide and the HLA-A*0201/peptide binding affinities. A set of
      102 peptides having affinity with the class I MHC HLA-A*0201 molecule was used as
      training set. A test set of 40 peptides was used to determine the predictive
      value of the models. The 3D-QSAR models yielded a q2 = 0.5724 and a high rpred2 =
      0.6955. The standard regression coefficients indicated that the hydrophobic
      interactions played an important role in peptide-MHC molecule binding and
      predicted the specific amino acid residue essential at a certain position of the
      peptide. The approach tested in the current paper is highly complementary to many
      of the methods described in references and possesses good predictability. It is a
      rapid and convenient method to detect high affinity peptide epitopes.

PMID- 15579239
TI  - A statistically driven approach for image segmentation and signal extraction in
      cDNA microarrays.
AB  - The increasing use of cDNA microarrays necessitates the development of methods
      for extracting quality data. Here, we set forth hurdles to overcome in image
      analysis of microarrays. We emphasize the importance of objective data extraction
      methods resulting in reliable signal estimates. Based on statistical principles,
      we describe a method for automated grid alignment, spot detection, background
      estimation, flagging, and signal extraction. A software application that we call
      SignalViewer has been implemented for this method. We identify areas where we
      improved upon current methods used for array image analysis at each step in the
      process. Finally, we give examples to illustrate the performance of our
      algorithms on raw data.

PMID- 15579240
TI  - Sample size for identifying differentially expressed genes in microarray
      experiments.
AB  - Microarray technology allows simultaneous comparison of expression levels of
      thousands of genes under each condition. This paper concerns sample size
      calculation in the identification of differentially expressed genes between a
      control and a treated sample. In a typical experiment, only a fraction of genes
      (altered genes) is expected to be differentially expressed between two samples.
      Sample size determination depends on a number of factors including the specified
      significance level (alpha), the desired statistical power (1-beta), the fraction
      (eta) of truly altered genes out of the total g genes studied, and the effect
      sizes (Delta) for the altered genes. This paper proposes a method to calculate
      the number of arrays required to detect at least 100lambda % (where 0 < lambda <
      or = 1) of the truly altered genes under the model of an equal effect size for
      all altered genes. The required numbers of arrays are tabulated for various
      values of alpha, beta, Delta, eta, and lambda for the one-sample and two-sample t
      tests for g = 10,000. Based on the proposed approach, to identify up to 90% of
      truly altered genes among the unknown number of truly altered genes, the
      estimated numbers of arrays needed appear to be manageable. For instance, when
      the standardized effect size is at least 2.0, the number of arrays needed is less
      than or equal to 14 for the two-sample t-test and is less than or equal to 10 for
      the one-sample t-test. As the cost per array declines, such array numbers become
      practical. The proposed method offers a simple, intuitive, and practical way to
      determine the number of arrays needed in microarray experiments in which the true
      correlation structure among the genes under investigation cannot be reasonably
      assumed. An example dataset is used to illustrate the use of the proposed
      approach to plan microarray experiments.

PMID- 15579241
TI  - Markov-modulated Markov chains and the covarion process of molecular evolution.
AB  - The covarion (or site specific rate variation, SSRV) process of biological
      sequence evolution is a process by which the evolutionary rate of a
      nucleotide/amino acid/codon position can change in time. In this paper, we
      introduce time-continuous, space-discrete, Markov-modulated Markov chains as a
      model for representing SSRV processes, generalizing existing theory to any model
      of rate change. We propose a fast algorithm for diagonalizing the generator
      matrix of relevant Markov-modulated Markov processes. This algorithm makes
      phylogeny likelihood calculation tractable even for a large number of rate
      classes and a large number of states, so that SSRV models become applicable to
      amino acid or codon sequence datasets. Using this algorithm, we investigate the
      accuracy of the discrete approximation to the Gamma distribution of evolutionary
      rates, widely used in molecular phylogeny. We show that a relatively large number
      of classes is required to achieve accurate approximation of the exact likelihood
      when the number of analyzed sequences exceeds 20, both under the SSRV and among
      site rate variation (ASRV) models.

PMID- 15579242
TI  - A preprocessor for shotgun assembly of large genomes.
AB  - The whole-genome shotgun (WGS) assembly technique has been remarkably successful
      in efforts to determine the sequence of bases that make up a genome. WGS assembly
      begins with a large collection of short fragments that have been selected at
      random from a genome. The sequence of bases at each end of the fragment is
      determined, albeit imprecisely, resulting in a sequence of letters called a
      "read." Each letter in a read is assigned a quality value, which estimates the
      probability that a sequencing error occurred in determining that letter. Reads
      are typically cut off after about 500 letters, where sequencing errors become
      endemic. We report on a set of procedures that (1) corrects most of the
      sequencing errors, (2) changes quality values accordingly, and (3) produces a
      list of "overlaps," i.e., pairs of reads that plausibly come from overlapping
      parts of the genome. Our procedures, which we call collectively the "UMD
      Overlapper," can be run iteratively and as a preprocessor for other assemblers.
      We tested the UMD Overlapper on Celera's Drosophila reads. When we replaced
      Celera's overlap procedures in the front end of their assembler, it was able to
      produce a significantly improved genome.

PMID- 15579243
TI  - DNA sequencing by hybridization using semi-degenerate bases.
AB  - One way to enhance the performance of hybridization microarrrays for DNA de novo
      sequencing is the use of probing patterns with gaps of unsampled positions.
      Ideally, such gaps could be realized by the inclusion into microarray oligos
      (probes) of wild-card compounds, referred to as universal bases (which bind
      nonspecifically to natural bases). The suggested alternative is to deploy in the
      gap positions degenerate bases, i.e., uniform mixtures of the four natural bases,
      with ensuing deterioration of the hybridization signal. In this paper, we show
      that such signal loss is a minor shortcoming, compared with the fact that
      degenerate bases cannot be treated as universal. Indeed, the substantial spread
      of hybridization energies at any microarray feature is such that on overwhelming
      number of mismatches bind more strongly than legal matches. We observed, however,
      that much narrower energy spreads are exhibited by pairs of bases in the same
      strength class (A-T and C-G). We call semi-degenerate a gap position realized
      with bases in the same energy class and show that well-known sequence
      reconstruction algorithms can be modified to achieve substantial improvements in
      sequencing effectiveness. For example, with a 4(9)-feature microarray and an
      acceptable weakening of the hybridization signal, one may achieve lengths of
      about 4,000 bases (compared with < 250 of the standard uniform method). Our
      approach also incorporates the use of a spectrum expressed in terms of observed
      feature melting temperatures (analog spectrum), rather than binary decisions made
      directly at the biochemical level (digital spectrum). While universal bases
      represent the ultimate goal of sequencing by hybridization, semidegenerate
      natural bases are the most effective known substitute.

PMID- 15579244
TI  - Fast optimal genome tiling with applications to microarray design and homology
      search.
AB  - In this paper, we consider several variations of the following basic tiling
      problem: given a sequence of real numbers with two size-bound parameters, we want
      to find a set of tiles of maximum total weight such that each tiles satisfies the
      size bounds. A solution to this problem is important to a number of computational
      biology applications such as selecting genomic DNA fragments for PCR-based
      amplicon microarrays and performing homology searches with long sequence queries.
      Our goal is to design efficient algorithms with linear or near-linear time and
      space in the normal range of parameter values for these problems. For this
      purpose, we first discuss the solution to a basic online interval maximum problem
      via a sliding-window approach and show how to use this solution in a nontrivial
      manner for many of the tiling problems introduced. We also discuss NP-hardness
      results and approximation algorithms for generalizing our basic tiling problem to
      higher dimensions. Finally, computational results from applying our tiling
      algorithms to genomic sequences of five model eukaryotes are reported.

PMID- 15579253
TI  - Biological energy sources: the surface energy and the physical chemistry of
      water. Examples from studies on muscle contraction.
AB  - The physical chemistry of water at nanometre dimensions was used to explain the
      conformational changes and water breaking properties of the glucose transporter
      protein (GLUTI) in human erythrocytes more than ten years ago. The energy for
      this hidden work arises from cycles of evaporation and condensation of water
      within the cells but was several times larger than resting metabolism. Physical
      chemical principles can quantify the hidden work done and demonstrate that a
      significant source of energy is available, which is free of the metabolic energy
      derived from the hydrolysis of ATP. Therefore, a more widespread biological use
      of this "free" energy source was probable and a working hypothesis, which applied
      this energy to supplement the work derived from ATP hydrolysis in muscle, was
      proposed. The scheme gives a complete explanation for the unexpected and novel
      findings in skeletal muscle reported from Italy. The problem of using two energy
      sources and the novel properties of water at nanometer dimensions as they would
      apply in muscle are briefly discussed but they merit further interdisciplinary
      studies.

PMID- 15579254
TI  - Elemental maps in human allantochorial placental vessels cells. 4. Isoproterenol
      and sodium nitroprusside effects.
AB  - The ionic channels (particularly, K+ and Ca2+ channels) regulate, via the
      membrane potential, the ionic distribution into the vascular cells. Micro
      particule induced X-ray emission (PIXE) analysis was applied to determine the
      ionic composition of vascular smooth muscle cells (VSMCs) and of vascular
      endothelial cells (VECs) in the placental human allantochorial vessels in a
      physiological medium (Hanks' solution) modified by the addition of a NO donor
      (sodium nitroprusside, SNP) and of a beta-adrenergic stimulator (isoproterenol,
      ISO). The addition of SNP or ISO induced no modification of the Na, K, Cl, P, S,
      Mg and Ca concentrations in VSMCs. In VECs, a same effect was observed except an
      increase of the Mg concentration with ISO. Theses results indicated a retroactive
      control (active feedback) of the internal ionic distribution by endothelial
      factors, ionic channels and exchangers.

PMID- 15579255
TI  - Ionizing radiation-induced macrophage activation: augmentation of nitric oxide
      production and its significance.
AB  - Radiation is an important therapy for many kinds of cancer. However, it can
      result in the inflammation and accompanying injury. Recently, it is being
      recognized that the nitric oxide (NO) produced in macrophages activated by
      ionizing radiation is an important mediator. Ionizing radiation has been
      confirmed to potentiate NO production in macrophages, though the mechanism is not
      clear. We have shown that the increase of NO production in irradiated macrophages
      contributed to tumoricidal activity, with the activation mechanisms differing
      between high-dose and low-dose irradiation. High-dose irradiation activates
      macrophages directly, whereas low-dose irradiation acts indirectly through
      interaction with neighboring cells and the paracrine induction of cytokines. In
      this review, we discuss the augmentation of NO production in macrophages by
      ionizing radiation and its mechanism and significance. In radiotherapy, the
      control of NO levels both in whole-body and in the tumor is important to prevent
      irradiation-induced injury and for the cancer to regress.

PMID- 15579256
TI  - Alveolar macrophages in chronic obstructive pulmonary disease (COPD).
AB  - Alveolar macrophages play a critical role as orchestrators of inflammation in
      chronic obstructive pulmonary disease (COPD). The numbers of alveolar macrophages
      are markedly increased in the lungs of patients with COPD as a result of
      increased recruitment, proliferation and survival. Alveolar macrophages secrete
      many inflammatory mediators, oxidants, proteins and proteinases in response to
      cigarette smoke extract and other stimuli. In COPD there is amplified secretion
      of these inflammatory products which may be related to defective histone
      deacetylase-2, which may also account for the steroid resistance of these cells
      in COPD patients. There are several novel therapeutic strategies targeted at
      macrophages.

PMID- 15579257
TI  - Interactions between pulmonary surfactant and alveolar macrophages in the
      pathogenesis of lung disease.
AB  - This article reviews recent findings regarding interrelationships between the
      pulmonary surfactant system and alveolar macrophages in the pathogenesis of human
      lung diseases, including pulmonary alveolar proteinosis, pulmonary infection,
      inflammation and obstructive lung diseases. Various components of pulmonary
      surfactant interact with alveolar macrophages in the modulation of innate host
      defense responses of the lung. In a reciprocal manner, alveolar macrophages
      regulate surfactant homeostasis, influencing rates of surfactant protein and
      phospholipid clearance and catabolism. Increasing evidence suggests that the
      complex interactions between the surfactant system and the alveolar macrophage
      are intrinsically linked to development of various lung diseases.

PMID- 15579258
TI  - Functional age-dependent changes in bronchoalveolar lavage rat cells.
AB  - Alveolar macrophages (AM) are located at the first line of non-specific defense
      against inhaled antigens in the lower respiratory tract and therefore represent
      the major effector cell in antimicrobial defense. Since children under 2 years
      are known to manifest increased susceptibility to lung infections we used a rat
      model to study functional capacities of the AM during different stages of
      development We analyzed several steps of the phagocytic process (adherence,
      chemotaxis and ingestion) as well as two different mechanisms of cytotoxicity
      [antibody dependent cellular cytotoxicity (ADCC) and cytotoxicity triggered by
      immune complex (ICC)] and tumor necrosis factor (TNF-alpha) secretion. We used
      young (4-6 weeks old), intermediate (16-25 weeks old) and adult (36-45 weeks old)
      rats. Adherence and phagocytic capacities of AM were lower in young rats compared
      to intermediate and adult animals. Chemotaxis towards the C5a complement
      component was low in the first two months of life, then it increased in the
      intermediate group and fell again in adults. Bronchoalveolar lavage (BAL) cells
      from young rats did not produce detectable TNF-alpha levels even when stimulated
      with phorbol 12-myristate 13-acetate (PMA). When we studied two different
      cytotoxic mechanisms we found that ICC markedly declines from youth to adulthood
      while ADCC showed a steady increase from youth to adulthood. In conclusion, our
      data show differences that may help to explain in part the enhanced
      susceptibility to pulmonary infections found in young children.

PMID- 15579259
TI  - Vocal buffering of the stress response: exposure to conspecific vocalizations
      moderates urinary cortisol excretion in isolated marmosets.
AB  - For many species, the presence of a significant social partner can lessen the
      behavioral and physiological responses to stressful stimuli. This study examined
      whether a single, individually specific, signature vocalization (phee call) could
      attenuate the physiological stress response that is induced in marmosets by
      housing them in short-term social isolation. Utilizing a repeated-measures
      design, adult marmosets (n=10) were temporarily isolated from their long-term
      pair mate and exposed to three conditions: signature vocalizations from the pair
      mate, phee calls from an unfamiliar opposite sex individual, or no auditory
      stimuli. Levels of urinary cortisol were monitored as a physiological indicator
      of the stress response. Urinary cortisol levels were also monitored, while
      subjects remained undisturbed in their home cages to provide baseline levels.
      Temporarily isolated marmosets showed significantly higher levels of urinary
      cortisol than undisturbed marmosets. However, the nature of the acoustic stimulus
      experienced during isolation led to differences in the excretion of urinary
      cortisol. Isolated marmosets exposed to a familiar pair mate's vocalization
      showed significantly lower levels of urinary cortisol than when exposed to
      unfamiliar marmoset vocalizations (P <0.04) or to no auditory stimuli (P <0.03).
      Neither the duration of pairing nor the quality of relationship in the pair
      (indexed by spatial proximity scores) predicted the magnitude of reduction in
      cortisol in the familiar vocalization condition. The results presented here
      provide the first evidence that a single, individually specific communication
      signal can decrease the magnitude of a physiological stress response in a manner
      analogous to the physical presence of a social partner, a process we term "vocal
      buffering."

PMID- 15579260
TI  - A daily rhythm in mating behavior in a diurnal murid rodent Arvicanthis
      niloticus.
AB  - The time of day at which mating occurs is dramatically different in diurnal
      compared to nocturnal rodents. We used a diurnal murid rodent, Arvicanthis
      niloticus, to determine if inverted rhythms in responsiveness to hormones
      contribute to this difference. Male and hormone-primed female grass rats were
      tested for mating behavior at four different times of day (ZT 5, 11, 17, 23; ZT
      0=lights-on). In females, there was considerable inter-individual variability
      with respect to patterns of responsiveness to hormones. Overall, the lordosis
      quotient (LQ) was rhythmic with a single peak just before lights-on (ZT 23);
      however, while roughly half of the females (7/15) exhibited this clear daily
      rhythm, the remaining animals (8/15) had relatively high LQs that did not change
      as a function of time. Males had their shortest ejaculation latencies and their
      highest number of ejaculations at ZT 23. Rhythms in mount frequency and post
      ejaculatory refractory period were bimodal, with peaks around lights-on and -off
      (ZT 23 and 11). This temporal pattern of mounting behavior closely parallels
      previously documented patterns of general activity, whereas rhythms in the more
      reflexive components of sex behavior (LQ and ejaculation) had more restricted
      peaks that coincided with just the onset of rhythms in general activity. These
      rhythms in sexual behavior are essentially reversed relative to those previously
      documented in lab rats.

PMID- 15579261
TI  - Neuroendocrine and behavioral response to social confrontation: residents versus
      intruders, active versus passive coping styles.
AB  - We investigated in the present study the neuroendocrine correlates in intruder
      and resident rats of a social confrontation. Adult male Wistar rats (intruders)
      were introduced into the home cage of a well-trained resident to induce
      characteristic agonistic interactions including physical attacks prior to
      separation by a wire mesh. The hypothalamic-pituitary-adrenal (HPA) axis activity
      and the intrahypothalamic release of arginine vasopressin (AVP) were monitored
      via chronically implanted jugular venous catheters and microdialysis probes aimed
      at the hypothalamic paraventricular nucleus (PVN), respectively. Based on the
      behavioral data collected during the 30-min confrontation, intruders and
      residents were additionally classified into two different subgroups: intruders
      which showed almost no freezing behavior (active copers) versus those showing
      pronounced freezing behavior (passive copers) and residents which were either
      predominantly aggressive or non-aggressive. The neuroendocrine data show that
      social confrontation caused a significantly increased secretion of the
      adrenocorticotropic hormone (ACTH) into plasma in both intruder subgroups,
      independently of their coping strategy. In contrast, plasma ACTH in residents was
      increased in response to social confrontation in non-aggressive animals only,
      whereas aggressive residents failed to mount an ACTH response. Interestingly,
      plasma AVP decreased in response to social confrontation in active intruders. As
      measured in microdialysates, the two groups of residents and passive intruders
      failed to show significant changes of intra-PVN release of AVP. In contrast, an
      increased release of this neuropeptide within the PVN could be monitored for
      active intruders. The data of the present study suggest that the different
      interpretation of an aversive encounter results in differences in the
      neuroendocrine response and intrahypothalamic vasopressinergic signaling in
      intruders versus residents.

PMID- 15579262
TI  - Neonatal manipulation of oxytocin influences female reproductive behavior and
      success.
AB  - During early neonatal development, oxytocin (OT) may influence the expression of
      adult behavior and physiology. Here we test the prediction that early postnatal
      exposure to OT or an oxytocin antagonist (OTA) can affect the subsequent
      expression of sexual receptivity and reproductive success of females. To test
      this hypothesis, female prairie voles (Microtus ochrogaster) received one of four
      treatments within 24 h of birth. Three groups received an intraperitoneal
      injection of OT, OTA, or isotonic saline. A fourth group was handled, but not
      injected. Around 75 days of age, females were paired with sexually experienced
      males for 72 h and sexual activity was recorded. Treatment had no effect on the
      probability of mating. Injection, regardless of treatment, reduced latency to
      mate compared with handled controls. OT and OTA treatment decreased mating bout
      frequency compared to saline and handled controls, while OTA treatment increased
      reproductive success, probability of successfully producing a litter. The results
      suggest that neonatally OT, both endogenous and exogenous, can affect the
      expression of adult female reproductive activity and that blocking the effects of
      endogenous OT during neonatal development can affect female reproductive success.
      Finally, the results suggest that a number of aspects of reproduction are
      regulated by OT during the postnatal period, but that the mechanism of action may
      differ depending upon the reproductive activity.

PMID- 15579263
TI  - Expression of nuclear receptor coactivators in androgen-responsive and 
      unresponsive motoneurons.
AB  - Adult rat lumbar motoneurons in the spinal nucleus of the bulbocavernosus (SNB)
      respond to androgens with an increase in soma size. This response is mediated by
      the androgen receptor (AR) in these motoneurons. Interestingly, other lumbar
      motoneurons in the rat possess the AR, yet do not respond to androgens in this
      fashion. This paradox suggests the existence and participation of nuclear
      receptor coregulators in conferring direct androgen-responsiveness to select
      motoneurons in the adult rat spinal cord. Nuclear receptor coregulators have
      received much attention recently for their proposed role in enhancing or
      repressing the transcriptional activity of steroid hormone receptors. The present
      study used immunocytochemistry to identify a number of nuclear receptor
      coactivators that are expressed by adult lumbar motoneurons: SRC-1, SRC-2, CBP,
      p300, and cJUN. Results of this study indicate that all five of these
      coactivators are abundantly expressed in the androgen-responsive SNB, and in two
      adjacent motor pools, the androgen-responsive dorsolateral nucleus (DLN), and the
      androgen-unresponsive retrodorsolateral nucleus (RDLN). While we detected
      significant regional differences for only SRC-1 and cJUN, the SNB consistently
      contained the highest percentage of immunoreactive motoneurons for all five
      cofactors examined. Our results indicate five different putative cofactors have
      the potential to participate in motoneuronal responses to androgens, since their
      distribution overlaps well with the distribution of ARs in these motoneurons.

PMID- 15579264
TI  - Elevated urinary testosterone excretion and decreased maternal caregiving effort
      in marmosets when conception occurs during the period of infant dependence.
AB  - The proximate mechanisms that regulate transitions in mammalian female
      reproductive effort have not been widely studied. However, variation in
      circulating levels of the androgenic steroid hormone testosterone (T) appears to
      mediate a trade-off between investment in current and future offspring in males
      [Ketterson, E.D., Nolan, V., Jr., 1992. Hormones and life histories: an
      integrative approach. Am. Nat. 140, S33-S62; Ketterson, E.D., Nolan, V., Jr.,
      1994. Hormones and life histories: an integrative approach. In: L.A. Real (Ed.),
      Behavioral Mechanisms in Evolutionary Ecology, University of Chicago Press,
      Chicago, pp. 327-353; Ketterson, E. D., Nolan, V., Jr., 1999. Adaptation,
      exaptation, and constraint: A hormonal perspective. Am. Nat. 154S, S4-S25]. The
      purpose of this study was to investigate the possibility that T is also
      associated with transitions in the reproductive effort of females, by examining
      the relationship between urinary T excretion, maternal caregiving behavior, and
      the timing of the postpartum conception in female Wied's black tufted-ear
      marmosets (Callithrix kuhlii). We examined the maternal carrying effort and
      peripartum T profiles of six females across two conditions: (1) when they
      conceived during the period of infant dependence (DPID), such that gestation was
      coupled with lactation; and (2) when the same females conceived after the period
      of infant dependence (APID). We also assessed the relationship between postpartum
      T levels and caregiving effort. When female marmosets conceived DPID, they
      dramatically reduced their caregiving effort, and had higher levels of urinary T,
      relative to when they conceived APID. Further, the litter-to-litter changes in
      maternal caregiving effort that we observed were related to variation in urinary
      T excretion; as weekly levels of urinary T excretion increased, concurrent
      caregiving effort declined. Our results suggest that variation in T secretion may
      regulate transitions in female reproductive behavior, and that the regulation of
      male and female parental behavior may be mediated by homologous neuroendocrine
      mechanisms.

PMID- 15579265
TI  - A masculinized skeletomusculature is not necessary for male-typical patterns of
      food-protective movement.
AB  - Although sexual dimorphism in movement has been documented in rodents, the extent
      to which it relates to dimorphic neural control versus dimorphic body
      size/structure is unclear. We have shown previously that male and female rats are
      sexually dimorphic with regards to the lateral movements and hindpaw stepping
      they use to protect a food item. We addressed the question of whether this sexual
      dimorphism is due to sex differences in peripheral skeletomusculature or in the
      CNS by examining the movement composition used during dodging to protect a food
      item by tfm-affected males and their wild-type male (WTM) and female (WTF)
      controls. The tfm-affected male, while genetically male, develops internal testes
      that secrete testosterone, but is phenotypically female due to a failure of
      androgen receptor-mediated masculinization of the periphery. Masculinization of
      the CNS of tfm-affected males, however, is primarily accomplished by the actions
      of testosterone's aromatized metabolite estradiol acting via estrogen receptors.
      Thus the tfm-affected male provides an assay by which the relative contributions
      of the skeletomusculature or CNS to sex differences in movement organization can
      be addressed. We found that female wild-type animals were significantly different
      from both the tfm-affected and wild-type males. There were no significant
      differences in dodge patterns used by tfm-affected males and their wild-type male
      controls. This study provides evidence that the sex differences in dodging
      patterns are mediated primarily by CNS mechanisms and are not primarily dependent
      on a male- or female-typical skeletomusculature.

PMID- 15579266
TI  - Neuroendocrine response to female ovulatory odors depends upon social condition
      in male common marmosets, Callithrix jacchus.
AB  - Male mammals show rapid behavioral and hormonal responses to signals from
      sexually receptive females. However, rapid endocrine responses to female signals
      have not been observed in a nonhuman primate. Here, we tested the behavioral and
      hormonal response of male common marmosets (Callithrix jacchus) to isolated scent
      secretions from ovulatory females or to vehicle control scent. Fifteen males were
      tested in their home cage for behavioral and hormonal responses. These males
      showed increased investigative and arousal behaviors to the ovulatory scent
      compared to the vehicle scent. Time sniffing the scent substrate and the duration
      of erections were significantly elevated in relation to the vehicle scent. Thirty
      minutes after presentation of ovulatory scent, males showed a significant
      increase in testosterone compared to the vehicle, but there was no difference in
      cortisol values. To better control for scent presentation, 15 additional males
      were tested under a controlled scent exposure. Current social housing condition
      influenced the male's testosterone response to the ovulatory scent. Single and
      paired males showed significant increases in testosterone levels with the
      ovulatory scent but did not increase cortisol levels. Single males also showed
      the highest change in testosterone with the ovulatory scent, but fathers showed
      no changes. These results indicate that a rapid hormonal response to sexually
      arousing cues occurs in marmosets, and the data suggest that a male's social
      condition influences how he responds to sexually relevant cues.

PMID- 15579267
TI  - Corticosterone secretion induced by chronic isolation in neonatal rats is
      sexually dimorphic and accompanied by elevated ACTH.
AB  - Rat pups repeatedly subjected to brief periods of isolation during the stress
      hyporesponsive period (SHRP) exhibit varied neuroendocrine and behavioral changes
      as neonates and as adults. For example, neonatal rats exhibit increased
      circulating corticosterone after 1-h isolation on postnatal day 9 (P9) only if
      they were isolated daily from P2 to P8 [McCormick, C.M., Kehoe, P., Kovacs, S.,
      1998. Corticosterone release in response to repeated, short episodes of neonatal
      isolation: evidence of sensitization. Int. J. Dev. Neurosci. 16, 175-185]. It is
      not known if the increase in adrenocortical response on P9 following repeated
      isolation is mediated by increased pituitary ACTH secretion. The present study
      examined the responsivity of the hypothalamic-pituitary-adrenal (HPA) axis during
      the SHRP following brief, repeated isolation or acute pharmacological
      manipulation. Removal from the nest for 1 h daily on P4-8 increased circulating
      corticosterone after 1-h isolation on P9 by approximately twofold. Neither
      unhandled nor handled controls showed a corticosterone response to 1-h isolation
      on P9. The increased corticosterone was sexually dimorphic, with only females
      showing the sensitization response. Other findings suggest that the hormonal
      response is centrally mediated; chronically isolated pups of both sexes exhibit
      increased plasma ACTH following 1-h isolation on P9. While we could not detect an
      increase in Fos immunoreactivity (IR) on P9 in the hypothalamic paraventricular
      nucleus (PVN) of chronically isolated pups, acute pharmacological activation of
      serotonin 2A/2C receptors produced robust activation of ACTH and corticosterone
      secretion as well as expression of Fos in the PVN on P9. We conclude that chronic
      isolation stress limited to the SHRP stimulates the neonatal HPA axis, and that
      the adrenal response is sexually dimorphic. In addition, PVN neurons can express
      Fos IR on P9 in response to a very potent activation of the HPA axis.

PMID- 15579268
TI  - Testosterone and group size in cliff swallows: testing the "challenge hypothesis"
      in a colonial bird.
AB  - The "challenge hypothesis" states that increases in testosterone levels of male
      animals during the breeding season are directly related to the extent of
      intrasexual competition for resources or mates that they experience. Although
      often tested in territorial species, the challenge hypothesis has not been
      evaluated for colonial animals that live in groups of different sizes and that
      thus experience different intensities of intrasexual competition. We measured
      circulating testosterone levels of male and female cliff swallows (Petrochelidon
      pyrrhonota) in southwestern Nebraska, where these birds nest in colonies of
      widely different sizes. Males had significantly higher testosterone levels than
      females, as expected. For males especially, there was a seasonal rise in
      testosterone levels early in the nesting cycle, corresponding to the period when
      birds were establishing nest ownership and egg laying, and then a fall as they
      switched to parental duties. Testosterone levels varied significantly with colony
      size; for both sexes, birds in larger colonies had higher levels of testosterone
      than those in smaller colonies when controlling for date. Age and body mass were
      not related to testosterone levels. Higher levels of testosterone for birds of
      both sexes in larger colonies probably reflect greater competition for matings,
      often extra pair, in the more social nesting situations. The results support the
      predictions of the challenge hypothesis.

PMID- 15579269
TI  - The sexually active states of free-ranging male African elephants (Loxodonta
      africana): defining musth and non-musth using endocrinology, physical signals,
      and behavior.
AB  - Musth in male African elephants, Loxodonta africana, is associated with increased
      aggressive behavior, continuous discharge of urine, copious secretions from the
      swollen temporal glands, and elevated androgen levels. During musth, bulls
      actively seek out and are preferred by estrous females although sexual activity
      is not restricted to the musth condition. The present study combines recently
      established methods of fecal hormone analysis with long-term observations on male
      female associations as well as the presence and intensity of physical signals to
      provide a more detailed picture about the physical, physiological, and behavioral
      characteristics of different states of sexual activity in free-ranging African
      elephants. Based on quantitative shifts in individual bull association patterns,
      the presence of different physical signals, and significant differences in
      androgen levels, a total of three potential sub-categories for sexually active
      bulls could be established. The results demonstrate that elevations in androgen
      levels are only observed in sexually active animals showing temporal gland
      secretion and/or urine dribbling, but are not related to the age of the
      individual. Further, none of the sexually active states showed elevated
      glucocorticoid output indicating that musth does not represent an HPA-mediated
      stress condition. On the basis of these results, we suggest that the term "musth"
      should be exclusively used for the competitive state in sexually active male
      elephants and that the presence of urine dribbling should be the physical signal
      used for defining this state.

PMID- 15579270
TI  - Testing the prenatal androgen hypothesis: measuring digit ratios, sexual
      orientation, and spatial abilities in adults.
AB  - The present study examined whether the following variables putatively associated
      with prenatal androgens are inter-related in women: spatial abilities, sexual
      orientation, and 2nd to 4th finger (digit) length ratio (2D:4D). Participants
      were 99 healthy premenopausal women tested in the menstrual phase of the ovarian
      cycle between 0800 and 0930 hr. Women completed the Kinsey scales of sexual
      orientation, and were either strictly heterosexual (HS; N=79) or not-strictly
      heterosexual (NHS; N=20). Photocopies of the two hands were collected, and
      participants completed the revised Vandenberg Mental Rotations test, the Paper
      Folding test, and a short version of the Guilford-Zimmerman Spatial Orientation
      Test. Results showed that NHS women exhibited superior spatial ability relative
      to HS women. No significant difference was found between the HS and NHS women in
      the 2D:4D digit ratio. There was no association between the digit ratio and
      spatial performance. These results support an association between increased
      spatial abilities and heteroflexible sexual orientation, which may possibly be
      mediated by high prenatal androgens.

PMID- 15579271
TI  - Sex differences in the relative lengths of metacarpals and metatarsals in
      gorillas and chimpanzees.
AB  - Sex differences other than the simple dimorphism in size were documented for the
      metapodials of two primate species. Lengths of metacarpals and metatarsals were
      obtained from the skeletons of 64 gorillas and 42 chimpanzees. Length ratios were
      constructed for all possible pairings of the five bones in each individual hand
      and foot. For both species, several of these length ratios exhibited substantial
      differences between the sexes. Body size was not the basis for these sex
      differences; when specimens of similar size were compared, the sex differences
      remained. In humans, length ratios for the fingers and toes also have previously
      been demonstrated to exhibit sex differences, and the length ratio for the index
      and ring fingers (the 2D:4D ratio) has been shown to correlate with various
      medical conditions. Various facts suggest that length ratios in human digits are
      associated with androgen exposure, probably during prenatal development. For
      gorillas, the metacarpal length ratio showing the largest sex difference was
      4Mc:5Mc in both hands, and the metatarsal length ratio showing the largest sex
      difference was 1Mt:2Mt in the left foot. Sex differences in length ratios also
      existed for chimpanzees, but they were generally smaller than for gorillas.
      Apparently, both gorillas and chimpanzees are affected by developmental
      mechanisms, possibly androgenic mechanisms, similar to those in humans. Analyses
      of previous measurements [Susman, R.L., 1979 Comparative and functional
      morphology of hominoid fingers. Am. J. Phys. Anthropol. 50, 215-236] revealed
      that all components of the rays are not affected equally by whatever mechanisms
      are responsible for the sex differences in length ratios.

PMID- 15579272
TI  - Experiential and hormonal correlates of maternal behavior in teen and adult
      mothers.
AB  - This study explores the role of cortisol and early life experiences in the
      regulation of maternal behavior and mood in teen and adult mothers. Primiparous
      mothers (n=119) (teen mothers < 19 years, n=42), young mothers (19-25 years, n=
      4), and mature mothers, (>25 years, n=43) were assessed for their maternal
      behavior, mood, and hormonal profile at approximately 6 weeks postpartum. Outcome
      measures were analyzed as a function of age and early life experience. Results
      showed an interaction between age and type of maternal behavior, where teen
      mothers engaged in more instrumental (e.g. changing diapers, adjusting clothes)
      less affectionate (e.g., stroking, kissing, patting) behavior, and mature mothers
      engaged in more affectionate and less instrumental behavior. When groups were
      reassessed based on early life experience (consistency of care during the first
      12 years of life: consistent care; having at least one consistent caregiver,
      inconsistent care; having multiple and changing caregivers), an interaction was
      also found between consistency of care and type of behavior shown, where mothers
      who received inconsistent care engaged in more instrumental and less affectionate
      behavior. Compared to mature mothers, teen mothers who were breast feeding also
      had higher salivary cortisol levels, and high cortisol in teen mothers related to
      decreased fatigue and increased energy. These results suggest that early life
      experiences are linked to mothering behavior and are consistent with the emerging
      human and animal literature on intergenerational effects of mothering style.

PMID- 15579274
TI  - HIV dementia: an evolving disease.
AB  - Several advances have led to improvements in the care and prognosis of HIV+
      individuals. The first is an understanding of the direct relationship between HIV
      replication and subsequent immunological and clinical progression, reinforcing
      the need to completely suppress HIV replication to control disease progression.
      The second is the wider availability of HAART which can provide effective
      suppression of HIV. The third major change is the ability to monitor HAART
      through the reliable and widespread measurement of plasma HIV RNA levels, which
      has become a routine part of clinical care. Since the introduction of highly
      active antiretroviral therapy (HAART) in the 1990s, there have been significant
      declines in the incidence rates of opportunistic infections in developed
      countries. HAART has clearly improved survival for individuals with HIV/AIDS, and
      has reduced the incidence of HIV-associated dementia (HIV-D) by 40-50% (Brodt et
      al., 2002). The prevalence of sensory neuropathies in advanced HIV/AIDS now
      exceeds 20% (Schifitto et al., 2002), and may rise further with prolonged
      exposure to neurotoxic HAART. HIV-D and HIV-related sensory neuropathies (HIV-SN)
      have a combined prevalence of about 30-50% in advanced HIV disease, suggesting
      that HAART does not provide complete protection against neurological damage
      (Bouwman et al., 1998). HIV-associated dementia (HIV-D) remains a common cause of
      dementia worldwide, and with HIV-related sensory neuropathies (HIV-SN) represents
      the commonest neurological disorders associated with AIDS. Furthermore, the
      temporal progression of HIV-D appears to have been altered by HAART, with most
      patients now showing an attenuated form of dementia, which with treatment is
      slowly progressive or static (Dougherty et al., 2002). This overview will review
      some of the outstanding questions relating to HIV-dementia, including: (a) are
      there differing phenotypes or temporal patterns of progression in HIV-dementia?
      (b) what determines these temporal patterns? and (c), what has been the impact of
      therapy on HIV dementia?

PMID- 15579275
TI  - Diminished matrix metalloproteinase 9 secretion in human immunodeficiency virus
      infected mononuclear phagocytes: modulation of innate immunity and implications
      for neurological disease.
AB  - Neurotoxic secretory products from virus-infected mononuclear phagocytes (MP;
      perivascular macrophages and microglia) orchestrate the neuropathogenesis of
      human immunodeficiency virus type one (HIV-1) infection. To uncover such MP
      products and their relationship to disease, we used a proteomics platform
      consisting of one dimensional polyacrylamide gel electrophoresis (1-DE), mass
      spectrometry peptide sequencing, and bioinformatics in order to identify from HIV
      1-infected monocyte-derived macrophages (MDM) secretions. Matrix
      metalloproteinase 9 (MMP 9) secreted in abundance in MDM was markedly down
      regulated following viral infection. A negative correlation between MMP 9 and HIV
      1 reverse transcriptase activity was shown by quantitative Western blot assays.
      These data further demonstrate immunoregulatory activities of HIV-1-infected MDM
      providing unique insights into cellular function in disease.

PMID- 15579276
TI  - Microarray analysis of changes in cellular gene expression induced by productive
      infection of primary human astrocytes: implications for HAD.
AB  - The role of astrocytes in HIV-1 associated dementia (HAD) is not well understood.
      HIV-1 binds efficiently to astrocytes but infects only a small fraction of the
      cells in vitro and in vivo. To gain insight into the biology of HIV-1-expressing
      astrocytes, we productively infected human fetal astrocytes with pseudotyped HIV
      1 and employed Affymetrix oligonucleotide microarrays to determine global changes
      in cellular gene expression at the peak of virus production. With a twofold
      change as a cutoff, HIV-1 increased transcription of 266 genes in astrocytes and
      suppressed expression of 468. The functions of highly expressed genes included
      interferon-mediated antiviral responses (OAS1, IFIT1), intercellular contacts
      (SH3, glia-derived nexin), cell homing/adhesion (matrix metalloproteinases), and
      cell-cell signaling (neuropilin 1 and 2). Surprisingly, genes involved in innate
      immune responses of astrocytes were largely unaffected. The single most
      significant effect of HIV-1, however, was down-modulation of at least 55 genes
      involved in control of cell cycle, DNA replication, and cell proliferation, which
      were overrepresented in these categories with probability scores of 10(-10)-10(
      26). Our data suggest that HIV-1 expression in astrocytes profoundly alters host
      cell biology, with potential consequences for the physiological function of
      astrocytes during HIV-1 infection in the brain.

PMID- 15579277
TI  - Microarray analysis of activated mixed glial (microglia) and monocyte-derived
      macrophage gene expression.
AB  - Since macrophage activation can now be studied at a global level using modern
      microarray and proteomic analyses, discovery of novel macrophage activation genes
      is inevitable and important for understanding HIV-associated dementia (HAD). We
      isolated two different types of primary human macrophages: microglia and monocyte
      derived macrophages (MDM) from brain tissue and whole blood, respectively. The
      microarray analysis of differentially regulated macrophage activation genes
      reported here supports our previous assertions that the mixed glia (MIX) cultured
      in starvation conditions (DMEM alone) are a non-activated, or "quiescent", tissue
      culture model for studying macrophage activation in the brain. Transcript levels
      from these quiescent cultures provided a background level of gene expression and
      allowed for the identification of upregulated macrophage activation genes in the
      MIX brain cultures upon treatment with an array of soluble activation factors:
      serum components, cytokines, and growth factors. We found that 914 genes in the
      MIX cultures and 734 genes in the MDM cultures had a greater than twofold
      increase in expression. We discovered 180 genes with expression that was
      increased more than twofold in both culture types. Microarray-specific
      statistical analyses were performed to complement fold change analysis:
      significance analysis of microarrays (SAM) and Partek Pro. In the MIX cultures,
      we detected over a 100-fold increase in IL-1beta and TIMP1 transcription; Caspase
      9, S100A8 and 9, MMP12, IL-8, monocyte chemotactic protein 1 (MCP1), MRC-1, and
      IL-6 were also upregulated. Activation of starved MDM cultures resulted in fewer
      upregulated genes compared to MIX cultures. Genes upregulated in both MIX and MDM
      included CCL2 (MCP1), CCL7, CXCL5, TNFSF14, kinases, and phosphatases. These
      microarray data may provide leads for identifying previously unknown neurotoxins,
      disease biomarkers, and pathways responsible for the neuronal apoptosis observed
      in HAD and for the eventual identification of therapeutic targets and treatments.

PMID- 15579278
TI  - Specific sequence configurations of HIV-1 LTR G/C box array result in altered
      recruitment of Sp isoforms and correlate with disease progression.
AB  - Basal and activated human immunodeficiency virus type 1 (HIV-1) long terminal
      repeat (LTR) activity, and in return, viral replication is partly dependent on
      interactions of the G/C box array with the Sp family of transcription factors.
      Analysis of LTR Sp binding site sequence variants revealed a C-to-T change at
      position 5 within Sp site III that increased in frequency and a 5T mutation
      within Sp site II, which decreased in frequency during the course of HIV disease.
      These results suggest LTR Sp binding site sequence variants may prove useful as
      viral molecular markers indicative of progressive HIV-1-induced disease.

PMID- 15579279
TI  - Substance P and neurokinin-1 receptor modulation of HIV.
AB  - There is a high incidence of life event stress, depression, and associated
      symptoms in individuals with HIV infection/AIDS. Psychological and psychiatric
      symptomatology in individuals with HIV and AIDS may be related to the progression
      of AIDS disease. The association between depression, anxiety, and stress with HIV
      disease progression suggests that neurobiologic and neurophysiologic factors have
      an important role in modulating HIV. The immune effects caused by changes in
      behavioral state or brain activity are affected, at least in part, through the
      neuroendocrine-immune pathways. Life stress and depression may be associated with
      altered blood levels of CNS-released neuropeptides, including substance P (SP).
      SP is a powerful immunomodulator which is a critical link between the nervous and
      immune system. We have investigated the role of the neuropeptide SP and its
      preferred receptor, neurokinin-1, in HIV infection and AIDS. There are compelling
      data from our laboratories, as well as the findings in the literature, which
      demonstrate that SP may play an important role in the pathophysiology of
      neuropsychiatric disorders, including stress and depression in HIV-infected
      individuals and in the immunopathogenesis of HIV disease. Modulation of SP
      activity and SP receptor may offer a novel approach to the treatment of
      psychiatric disorders and to the design of new anti-HIV therapy.

PMID- 15579280
TI  - Drug abuse and neuropathogenesis of HIV infection: role of DC-SIGN and IDO.
AB  - Dendritic cells are the critical mediators of various immune responses and are
      the first line of defense against any infection including HIV. They play a major
      role in harboring HIV and the subsequent infection of T cells and passage of
      virus through the blood-brain barrier (BBB). The recently discovered DC-specific,
      CD4-independent HIV attachment receptor, DC-SIGN, and T-cell suppressing factor,
      indolamine 2,3-dioxygenase (IDO), are known to play a critical role in the immuno
      neuropathogenesis of HIV infection. Since brain microvascular cells (BMVEC)
      express dendritic cell (DC)-specific C type ICAM-3 grabbing nonintegrin (DC
      SIGN), it is possible that DC-SIGN may play a critical role in human
      immunodeficiency virus-type 1 (HIV-1) infection and migration of infected DC
      across BBB. Matrix metalloproteinases (MMPs) are proteolytic enzymes known to be
      responsible for maintenance, turnover and integrity of extracellular matrix. Our
      results show that cocaine upregulates IDO and DC-SIGN expression by DC. Further,
      cocaine upregulates DC-SIGN and MMPs in BMVEC supporting the hypothesis that
      cocaine causes membrane permeability facilitating endothelial transmigration of
      infected DC in to the CNS. Targeting DC-SIGN and IDO with specific monoclonal
      antibodies, inexpensive synthetic antagonists, antisense oligonucleotides and
      siRNA may lead to develop novel treatment strategies particularly in high-risk
      populations such as cocaine users.

PMID- 15579281
TI  - Nuclear receptor activation and interaction with morphine.
AB  - Nervous system disease in HIV infection is associated with toxic damage induced
      by effects from proinflammatory responses and oxidative stress, and such effects
      may be more prominent among opioid abusers. In these studies, the effects of
      activating retinoid receptor (retinoic acid receptor (RAR) and retinoid X
      receptor (RXR)) and peroxisome proliferator activated receptor (PPAR) gamma,
      which belong to the steroid-lipid nuclear receptor family, on tumor necrosis
      factor (TNF)-alpha production and inducible nitric oxide synthase (iNOS) gene
      expression by stimulated U937 and SVG cells, respectively, were examined. Also
      studied were the effects of morphine on these responses. These studies showed
      that, in stimulated cells, the observed responses were suppressed by activation
      of the nuclear receptors as compared to non-stimulated control cells. Moreover,
      in phytohemagglutinin (PHA)-stimulated U937 cells, morphine reversed the TNF
      alpha suppression that was induced by LG101305 and ciglitazone. Preliminary data
      in SVG cells suggest a tendency for morphine to have a similar effect on LG101305
      exposed SVG cells stimulated with a combination of lipopolysaccharide (LPS) and
      interferon-gamma, whereas this effect was not induced when these cells were
      incubated with ciglitazone. Therefore, specific nuclear receptor activation may
      be potentially beneficial in the treatment of neurological disease associated
      with HIV infection and may show specific interactions with opioids. The
      mechanisms that underlie these effects require further study.

PMID- 15579282
TI  - Cerebrospinal fluid markers that predict SIV CNS disease.
AB  - Predictive cerebrospinal fluid markers would provide valuable tools for tracking
      the development and progression of HIV CNS disease. In this study, expression of
      IL-6, MCP-1, and viral RNA in cerebrospinal fluid collected from SIV-inoculated
      macaques during acute, asymptomatic, and terminal stages of infection was
      quantitated to determine whether one or several of these parameters paralleled
      the severity of SIV encephalitis. Animals that developed moderate to severe SIV
      encephalitis had significantly elevated levels of CSF IL-6, MCP-1, and SIV RNA
      during asymptomatic infection and persisting through terminal disease as compared
      to animals developing mild or no CNS disease.

PMID- 15579283
TI  - Investigations on four host response factors whose expression is enhanced in X4
      SHIV encephalitis.
AB  - HIV encephalopathy, one of the major complications of HIV infection, involves
      productive virus replication in macrophages in the brain in association with
      heightened expression of several host response factors. One or more of these
      factors are thought to be the cause of the degenerative changes in neurons in the
      brain. Macaques infected with SIV and SHIV viruses have provided excellent
      working models for studying mechanisms of the human disease. Although HIV
      encephalopathy is primarily associated with CCR5-utilizing viruses, our findings
      have shown that CXCR4-utilizing SHIVs were also capable of causing the syndrome
      in rhesus macaques. In SHIV-infected macaques, approximately 30% of the animals
      developed encephalitis. In order to understand the factors leading to end-stage
      encephalitis, we performed microarray analyses on brains of encephalitic and non
      encephalitic-infected macaques, and found pronounced enhancement of expression of
      interleukin-4, platelet-derived growth factor-B chain, monocyte chemoattractant
      protein-1 and CXCL10 in the brains of the encephalitic animals. This review
      discusses the role of each of these factors in mediating SHIV encephalitis.

PMID- 15579284
TI  - Acute SIV infection of the brain leads to upregulation of IL6 and interferon
      regulated genes: expression patterns throughout disease progression and impact on
      neuroAIDS.
AB  - The virus/host interactions during the acute phase of human immunodeficiency
      virus (HIV) infection help determine the course of disease. During this time
      period, virus enters the brain. Here, we report clusters of genes whose
      transcripts are significantly upregulated in the frontal lobe of the brain during
      acute simian immunodeficiency virus (SIV) infection of rhesus monkeys. Many of
      these genes are involved in interferon (IFN) and/or interleukin (IL)-6 pathways.
      Although neither IFNalpha nor IFNgamma are elevated in the brain, IL6 is
      increased. Both IFNalpha and IL6 are elevated in plasma during this acute phase.
      The upregulation of STAT1, verified by immunohistochemical staining, can be due
      to both central nervous system (CNS) (SIV and IL6) and peripheral (IFNalpha and
      IL6) causes, and can itself drive the expression of many of these genes.
      Examination of the levels of expression of the upregulated genes in the post
      acute and long-term phases of infection, as well as in SIV encephalitis, reveals
      increased expression throughout SIV infection, which may serve to protect the
      brain, but can have untoward long-term consequences.

PMID- 15579285
TI  - Invasive chronic inflammatory monocyte phenotype in subjects with high HIV-1
      viral load.
AB  - Human immunodeficiency virus type 1 (HIV-1)-infected monocytes trafficking into
      the central nervous system are a risk factor for HIV-1-associated dementia. We
      performed global gene expression analysis on CD14+ monocytes isolated from HIV-1
      infected individuals and controls to identify HIV-1-related changes in monocyte
      phenotype. Monocytes from subjects with high viral load (HVL) had a significant
      increase in monocytes expressing CD16, CCR5, and MCP-1. There was also an
      increase in sialoadhesin, a macrophage marker of chronic inflammation. Expression
      of proinflammatory cytokine genes IL-1, IL-6, and TNF-alpha was unchanged in
      individuals with HIV-1 compared to control CD14+ monocytes. Differential gene
      expression identified by DNA microarray analysis was confirmed with reverse
      transcription polymerase chain reaction (RT-PCR), while increased protein
      expression was characterized by immunofluorescence. We concluded that there is a
      circulating CD14+ macrophage hybrid phenotype in subjects with HVL.

PMID- 15579286
TI  - Amyloid precursor protein expression in circulating monocytes and brain
      macrophages from patients with HIV-associated cognitive impairment.
AB  - We examined amyloid precursor protein (APP) surface expression on circulating
      leukocytes and in brain tissues from normal individuals and HIV+ subjects with
      cognitive impairment. Most monocytes, and a subset of B-lymphocytes, expressed
      APP, while T-lymphocytes, granulocytes, and natural killer (NK) cells did not.
      CD14bright/CD16+ monocytes expressed the highest levels, and CD14dim/CD16+ cells
      were negative, suggesting a relationship with activation. Higher APP+ monocyte
      levels correlated with increased numbers of CD16+ monocytes, but not with the
      degree of cognitive impairment. Treatment of monocytes with M-CSF, but not LPS,
      upregulated APP expression. In the brain, APP appeared as axonal immunoreactivity
      and diffuse plaques, and APP+ perivascular macrophages were seen in cases with
      severe dementia. APP may facilitate monocyte entry into the brain.

PMID- 15579287
TI  - Acquired neuronal channelopathies in HIV-associated dementia.
AB  - A gene expression profile of the human brain cortex was performed in people with
      HIV-1-associated dementia (HAD) using Affymetrix HG-U133 chips. Messenger RNA
      transcripts in middle frontal gyrus from subjects with HAD or milder
      neurocognitive dysfunction were compared to HIV-negative people. The analysis
      focused on ionic conductance carriers that control membrane excitation.
      Overexpressed ionic channel genes in brain cortex of subjects with dementia
      included (1) a calcium-driven K+ channel that prolongs afterhyperpolarization
      (AHP) current, (2) a leak type of K+ channel that prolongs the AHP, (3) an
      adenosine receptor that modulates cationic current via G proteins, (4) a G
      protein-coupled serotonin receptor that modulates cyclic AMP-linked current
      transduction, (5) a G protein-coupled dopamine receptor, (6) a GABA receptor
      subunit that conducts chloride current. Underexpressed current generators in the
      demented subjects included (1) two voltage-gated K+ channels that influence
      refractory periods and the onset of AHP, (2) a Na+ channel subunit that modifies
      current inactivation and the onset of the AHP, (3) a neuronal type of voltage
      sensitive Ca+ channel that controls postsynaptic membrane excitability, (4) a
      metabotropic glutamate receptor that regulates cationic gating via G protein
      coupling, (5) A specific Galpha protein that transduces metabotropic cationic
      current, (6) an NMDA receptor subunit, (7) a glycine receptor subunit that
      modulates chloride current. These gene expression shifts probably occurred in
      neurons because they were not present in gyral white matter. Acquired neuronal
      channelopathies were not associated with a generalized shift of neuronal or glial
      cell markers, which suggest that they were not an artifact produced by
      neurodegeneration and/or glial cell proliferation. Channelopathies were not
      correlated with a generalized increase of inflammatory cell transcripts and were
      present in demented people without, and with HIV encephalitis (HIVE). We surveyed
      experimentally induced perturbations of these channels to determine the
      implications for brain function. Eleven experimental channelopathies produced
      decreased neuronal firing frequencies and pacemaker rates in model neurons; seven
      channelopathies increase neuronal firing rates experimentally. The implied
      disruption of neuronal excitability is consistent with some features of HAD,
      including its potential reversibility after HIV-1 replication is suppressed, the
      abnormal electroencephalographic recordings, the lack of clear-cut correlation
      with neurodegeneration and the lack of strict correlation with brain
      inflammation. The channelopathy concept may have wide relevance to the
      subcortical dementias.

PMID- 15579288
TI  - Identification of potential antibody markers in HIV-associated dementia.
AB  - Markers for HIV-associated dementia (HAD) are needed for diagnosis and
      management. Specific antibodies to brain and immune complexes (IC) in the
      cerebrospinal fluid (CSF) are potential markers. CSF IC were found in 4 of 4 HAD
      patients, 2 of 2 AIDS-central nervous system (CNS) lymphoma patients with
      dementia, 0 of 1 AIDS-CNS lymphoma patient without dementia, 0 of 1 AIDS-CNS
      toxoplasmosis patient without dementia, and 0 of 10 neurologic disease controls.
      By blinded immunoblots, antibrain antibodies in serum and CSF were found in 11 of
      12 HAD cases and 7 of 19 HIV-1 patients without HAD. All 11 non-HIV-1 controls
      were negative. These and published data suggest antibrain antibodies and IC may
      serve as markers of HAD.

PMID- 15579289
TI  - Immunophilin expression in the HIV-infected brain.
AB  - Immunophilins (IP) are receptors for immunosuppressive drugs and also aid protein
      folding, assembly, and trafficking. This autopsy study analyses the levels of
      FKBP12 in the brain of patients with HIV encephalitis. We show that the
      expression of FKBP12 is increased in the deep gray matter and frontal cortex
      where it colocalizes with markers of pathology. Changes in FKBP12 levels may be
      linked to the abnormal protein folding and axonal transport that characterize the
      neurodegenerative process and could also explain the selective vulnerability of
      the basal ganglia to HIV infection.

PMID- 15579290
TI  - Expression of the urokinase plasminogen activator and its receptor in HIV-1
      associated central nervous system disease.
AB  - The urokinase plasminogen activator (uPA) and its receptor (uPAR) play important
      physiological functions in extracellular proteolysis, as well as cell adhesion
      and migration. Through dysregulation of these functions, the uPA/uPAR system
      might be involved in the pathogenesis of AIDS dementia complex (ADC), and, in
      fact, uPAR has been found to be overexpressed in the cerebrospinal fluid (CSF)
      and brain tissues of patients with ADC. On the other hand, its ligand uPA has
      been shown to down-regulate HIV replication in vitro. In this study, we examined
      uPAR and uPA expression in the brain of HIV-related lesions, as well as CSF
      levels of soluble uPAR (suPAR), uPA, and complexes between these two molecules
      (suPAR/uPA) in patients with HIV infection with or without ADC. uPAR was highly
      expressed by macrophages in both HIV encephalitis (HIV-E) or leukoencephalopathy
      (HIV-LE), with a distribution exceeding that of HIV p24 antigen. In contrast, uPA
      was detected only on rare cells in most of the cases. Both uPA and suPAR/uPA
      complex concentrations were significantly correlated with CSF suPAR levels, and
      CSF concentrations of both markers were higher in ADC patients than controls.
      However, uPA levels were substantially lower than corresponding suPAR levels.
      Although these findings remain correlative, they add support to the hypothesis
      that uPAR might be an important participant in the events leading to ADC.
      Additionally, these findings are consistent with a model in which overexpression
      of uPAR and overproduction of its soluble form may promote HIV replication via
      binding and removal of uPA from cell surface.

PMID- 15579291
TI  - Neuroimaging correlates of HIV-associated BBB compromise.
AB  - The mechanisms underlying blood-brain barrier (BBB) compromise in human
      immunodeficiency virus (HIV) infection and the ways in which BBB compromise might
      impair neurocognitive function remain poorly understood. This study had two aims:
      (1) to examine the relationship between BBB breakdown, measured using contrast
      enhanced magnetic resonance imaging (CE-MRI), plasma viral load, and neurological
      status; and (2) to examine the influence of highly active antiretroviral therapy
      (HAART) on the relationship between neuroinflammation using myoinositol/creatine
      (mI/Cr), a surrogate marker of glial activation as measured by magnetic resonance
      spectroscopy (MRS), and BBB compromise determined by CE-MRI. In 25 HIV-infected
      patients, we found that: (1) the severity of neurocognitive impairment correlated
      with the degree of BBB breakdown in the basal ganglia; (2) for any given degree
      of BBB compromise, patients with high plasma viral load were more severely
      impaired; (3) BBB compromise correlated with mI/Cr in the basal ganglia; and (4)
      for any given level of mI/Cr, the severity of BBB compromise and the severity of
      neurocognitive impairment were significantly less in patients on HAART than in
      those who were HAART-naive. These results confirm a role for BBB compromise in
      the pathogenesis of HIV-associated neurocognitive impairment and suggest that
      elevated plasma viral load in the presence of BBB compromise may increase the
      risk for development of HIV-associated dementia (HAD). Additionally, they suggest
      a salutary effect of HAART on the incidence and severity of HAD, which may, in
      part, be due to protection of BBB integrity.

PMID- 15579292
TI  - Increased frontal white matter diffusion is associated with glial metabolites and
      psychomotor slowing in HIV.
AB  - Diffusion-weighted imaging (DWI) measures brain water diffusion that is sensitive
      to microscopic brain injury. A total of 11 HIV seropositive patients were
      compared to 14 seronegative subjects using DWI, proton magnetic resonance
      spectroscopy (1H MRS), and neuropsychological tests. The apparent diffusion
      coefficient (ADC) was significantly increased in the HIV patients, primarily in
      the frontal white matter (FWM; +5%, p=0.01). Diffusivity correlated positively
      with the glial marker myo-inositol (r=0.5, p=0.008) and negatively with cognitive
      performance (NPZ-8 composite score; r=-0.43, p=0.05). These findings suggest
      increased brain water diffusion may reflect increased glial activation or
      inflammation, which in turn, may contribute to the cognitive deficits in HIV
      patients.

PMID- 15579293
TI  - Neuroimaging in human immunodeficiency virus infection.
AB  - Human immunodeficiency virus (HIV) is associated with central nervous system
      (CNS) changes that may affect cerebral blood flow (CBF), metabolism, structure,
      and diffusion. Each of the available neuroimaging techniques offers unique
      insight into the neural mechanisms underlying HIV, as well as a potential means
      of monitoring disease progression and treatment response. The purpose of the
      article is to provide a review of experimental studies evaluating changes related
      to HIV with imaging techniques, including single-photon emission computed
      tomography (SPECT), positron emission tomography (PET), volumetric magnetic
      resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy
      (MRS), diffusion tensor imaging (DTI), and perfusion MRI (pMRI).

PMID- 15579294
TI  - Patterns of gene dysregulation in the frontal cortex of patients with HIV
      encephalitis.
AB  - The neurodegenerative process in HIV encephalitis (HIVE) is associated with
      extensive damage to the dendritic and synaptic structure that often leads to
      cognitive impairment. Several mechanisms might be at play, including release of
      neurotoxins, oxidative stress and decreased activity of neurotrophic factors.
      Furthermore, HIV-mediated dysregulation of genes involved in neuronal maintenance
      might play an important role. For this purpose, cRNA was prepared from the brains
      of 17 AIDS patients for analysis with the Affymetrix Human U95Av2 GeneChip and
      analyzed with the GeneSpring Expression Analysis Software. Out of 12,625 genes
      analyzed, 74 were downregulated and 59 were upregulated compared to controls.
      Initial alternative analysis of RNA was performed by ribonuclease protection
      assay (RPA). In cases with HIVE, downregulated genes included neuronal molecules
      involved in synaptic plasticity and transmission (ion channels, synaptogyrin,
      synapsin II), cell cycle (p35, p39, CDC-L2, CDC42, PAK1) and signaling molecules
      (PI3K, Ras-Raf-MEK1), transcription factors and cytoskeletal components (MAP-1B,
      MAP-2, tubulin, adducin-2). Upregulated genes included those involved in
      neuroimmune (IgG, MHC, beta2microglobulin) and anti-viral responses (interferon
      inducible molecules), transcription (STAT1, OLIG2, Pax-6) and signaling
      modulation (MEK3, EphB1) of the cytoskeleton (myosin, aduccin-3, radixin,
      dystrobrevin). Taken together, this study suggests that HIV proteins released
      from infected macrophages might not only induce a neuroinflammatory response, but
      also may promote neurodegeneration by interfering with neuronal transcription of
      genes involved in regulating signaling and cytoskeletal molecules important in
      maintaining synapto-dendritic functioning and integrity.

PMID- 15579295
TI  - Novel markers of oxidative stress in actively progressive HIV dementia.
AB  - Oxidative stress leads to the production of reactive oxygen species that can
      attack lipid membranes resulting in cellular dysfunction and death. Cellular
      redox state is closely linked to ceramide, sphingomyelin, and 4-hydroxynonenal
      (HNE) levels. We describe data showing increased levels of these oxidative stress
      markers in HIV encephalitis. In addition, actively progressing HIV dementia is
      associated with increases in HNE and ceramide, while inactive HIV dementia is
      associated with increases in sphingomyelin. These markers may be useful for
      distinguishing between different clinical phenotypes of HIV dementia.

PMID- 15579296
TI  - CCR2 polymorphisms affect neuropsychological impairment in HIV-1-infected adults.
AB  - CCR2 is a minor coreceptor for human immune deficiency virus-1 (HIV-1) and its
      impact on HIV-1-related neuropsychological impairment (NPI) remains unknown. We
      studied the impact of CCR2-V64I polymorphisms on the development of NPI in 121
      HIV-1 patients. The CCR2-64-I allele was associated with rate of progression to
      NPI when measured from the first study visit (Log Rank p=0.01) or from the
      estimated time of seroconversion (p=0.02). CCR2-V64I was not associated with
      plasma or CSF HIV-1 RNA load, suggesting that the impact of CCR2 on
      neuropathogenesis may involve alterations in inflammatory responses within the
      CNS rather than a direct impact on viral entry or replication.

PMID- 15579297
TI  - The monocyte chemotactic protein-1 -2578G allele is associated with elevated MCP
      1 concentrations in cerebrospinal fluid.
AB  - Because monocyte chemotactic protein (MCP)-1 is an important cofactor in HIV
      neuropathogenesis, we investigated the relationship between MCP-1 genotype and
      expression in cerebrospinal fluid (CSF). We evaluated a genetic polymorphism in
      the MCP-1 promoter at position -2578 (alternatively designated -2518) in 98 HIV
      infected subjects who had contemporaneously collected plasma and CSF. CSF MCP-1
      levels were highest in the G/G genotype group, intermediate in the G/A group, and
      lowest in the A/A group. MCP-1 levels in plasma only differed by genotype after
      adjusting for HIV-related factors. Our findings suggest that this MCP-1 promoter
      polymorphism influences HIV neuropathogenesis by regulating MCP-1 protein
      expression in the central nervous system (CNS).

PMID- 15579298
TI  - Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV
      Cohort.
AB  - There are discrepant findings regarding the risk of HIV-associated dementia (HAD)
      relating to apolipoprotein E4, suggesting other factors may modulate risk.
      Furthermore, evidence suggests a changing phenotype of HAD in the era of highly
      active antiretroviral therapy (HAART), prompting a need to determine if new
      disease markers have emerged. In this analysis, APOE genotype was determined for
      182 participants enrolled in the Hawaii Aging with HIV Cohort. After controlling
      for age and diabetes status, an independent risk of HAD relating to E4 was seen
      in older participants [OR=2.898 (1.031-8.244)] but not in younger participants
      [OR=0.373 (0.054-1.581)]. Several proposed mechanisms may underlie this
      association. Consideration of non-traditional risk factors for HAD in older HIV
      patients may yield new markers of disease in the era of HAART.

PMID- 15579299
TI  - Role of neurosteroids in catamenial epilepsy.
AB  - Catamenial epilepsy is a menstrual cycle-related seizure disorder that affects up
      to 70% of women with epilepsy. Catamenial epilepsy is characterized by an
      increase in seizures during particular phases of the menstrual cycle. Three
      distinct patterns of catamenial epilepsy - perimenstrual, periovulatory, and
      inadequate luteal phase - have been described. Currently, there is no specific
      treatment for catamenial epilepsy. The molecular mechanisms involved in the
      pathophysiology of catamenial epilepsy are not well understood. Recent studies
      suggest that cyclical changes of ovarian hormones estrogens (proconvulsant) and
      progesterone (anticonvulsant) appear to play a key role in the genesis of
      catamenial seizures. Progesterone reduces seizure susceptibility partly through
      conversion to neurosteroids such as allopregnanolone, which enhances GABA(A)
      receptor function and thereby inhibits neuronal excitability. In animal models,
      withdrawal from chronic progesterone and, consequently, of allopregnanolone
      levels in brain, has been shown to increase seizure susceptibility. Natural
      progesterone therapy has proven effective in women with epilepsy. Moreover,
      neurosteroids have been shown to be very effective inhibitors of catamenial
      seizures in animal models. Thus, synthetic neuroactive steroids, such as
      ganaxolone, which are orally active and devoid of hormonal side effects,
      represent a novel treatment strategy for catamenial epilepsy. However, their
      clinical efficacy in catamenial epilepsy has yet to be explored. A greater
      understanding of the molecular mechanisms is clearly needed for designing
      effective treatment and prevention strategies of catamenial epilepsy in women at
      risk.

PMID- 15579300
TI  - Chronic temporal lobe epilepsy: spatial extent and degree of metabolic
      dysfunction studied with magnetic resonance spectroscopy (MRS).
AB  - INTRODUCTION: Proton magnetic resonance spectroscopy ((1)H MRS) has been proposed
      as a lateralizing method for the presurgical evaluation of patients with
      medically intractable temporal lobe epilepsy (TLE). Studies have shown
      correlations between temporal lobe (TL) NAA and seizure frequency, and TL NAA/Cr
      and the duration of epilepsy in patients with TLE. This latter finding may
      suggest that progressive neuronal dysfunction may occur in both temporal lobes in
      patients with TLE, even when the seizures originate in only one temporal lobe. We
      analyzed our data in an attempt to find a possible correlation between extension
      of neuronal dysfunction based on NAA measures and duration of epilepsy. METHODS:
      We studied 45 consecutive patients with the diagnosis of TLE, who were referred
      for presurgical evaluation. Duration of epilepsy was defined as the interval
      between the age of seizure onset and the time of the MRS examination. All studies
      were performed in the inter-ictal state, prior to intracranial monitoring or
      resection. We performed two-tailed Pearson correlation analysis between
      ipsilateral NAA/Cr and extension of the abnormality (voxels involved) and the
      duration of the seizure disorder in years. RESULTS: The average duration of
      epilepsy in this group was 20 years. No significant correlation was found between
      duration of epilepsy and mean hippocampal NAA/Cr (r=-.131, p=.390); nor was a
      correlation found between duration of epilepsy in years or the extent of
      metabolic lesion (voxels involved) (r=-.264, p=.079). CONCLUSIONS: Hippocampal
      NAA/Cr does not correlate with duration of epilepsy in TLE. Our findings suggest
      that cross-sectional group measures of hippocampal neuronal function do not
      suggest damage progression.

PMID- 15579301
TI  - Electroclinical and magnetoencephalographic studies in epilepsy patients with
      polymicrogyria.
AB  - RATIONALE: Malformations of cortical development (MCDs) are increasingly
      recognized as important causes of developmental delay, epilepsy, and other
      neurological disorders. Polymicrogyria, a type of MCD, is characterized by many
      small microgyria separated by shallow sulci, a slightly thick cortex, neuronal
      heterotopia and often enlarged ventricles. The present descriptive study analysis
      the electroclinical and magnetoencephalographic findings of patients with
      epilepsy and polymicrogyria without schizencephaly. METHODS: We studied six
      patients; mean age was 27 years, who had evidence of polymicrogyria in
      neuroimaging studies. A single equivalent-current dipole (ECD) model was used to
      estimate the location of epileptiform spike dipole sources. Analysis was
      performed on selected data segments containing MEG spikes. MEG results were
      combined with MRI to create magnetic source images (MSI). RESULTS: In all cases
      we present results of MRI, MEG, Video-EEG monitoring, and other functional
      neuroimaging studies if performed. CONCLUSIONS: MSI can be used to accurately
      localize sources of epileptiform discharges. As such MSI can play a role of
      directly determining the functional epileptogenic significance of abnormalities
      depicted in imaging.

PMID- 15579302
TI  - Epilepsy induced by extended amygdala-kindling in rats: lack of clear association
      between development of spontaneous seizures and neuronal damage.
AB  - Most patients with temporal lobe epilepsy (TLE), the most common type of
      epilepsy, show pronounced loss of neurons in limbic brain regions, including the
      hippocampus, amygdala, and parahippocampal regions. Hippocampal damage in
      patients with TLE is characterized by extensive neuronal loss in the CA3 and CA1
      sectors and the hilus of the dentate gyrus. There is a long and ongoing debate on
      whether this type of hippocampal damage, referred to as hippocampal sclerosis, is
      the cause or consequence of TLE. Furthermore, hippocampal damage may contribute
      to the progressive features of TLE. The present study was designed to determine
      whether development of spontaneous recurrent seizures (SRS) after extended
      kindling of the amygdala in rats is associated with neuronal damage. The kindling
      model of TLE was chosen because previous studies have shown that only part of the
      rats develop SRS after extended kindling, thus allowing to compare the brain
      pathology of rats that received the same number of amygdala stimulation but did
      or did not develop SRS. For extended kindling, rats were stimulated twice daily 3
      5 days a week for up to about 280 stimulations. During long-term EEG/video
      monitoring, SRS were observed in 50% of the rats over the period of extended
      kindling. SRS often started with myoclonic jerks or focal seizures and
      subsequently progressed into secondarily generalized seizures, so that the
      development of SRS recapitulated the earlier kindling of elicited seizures. No
      obvious neurodegeneration was observed in the CA1 and CA3 sectors of the
      hippocampus, the amygdala, parahippocampal regions or thalamus. A significant
      bilateral reduction in neuronal density was determined in the dentate hilus after
      extended kindling, but this reduction in hilar cell density did not significantly
      differ between rats with and without observed SRS. Determination of the total
      number of hilar neurons and of hilar volume indicated that the reduced neuronal
      density in the dentate hilus was due to expansion of hilar area but not to
      neuronal damage. The data demonstrate that extended kindling does not cause any
      hippocampal damage resembling hippocampal sclerosis, but that SRS develop in the
      absence of such damage.

PMID- 15579303
TI  - Valproic acid doses, concentrations, and clearances in elderly nursing home
      residents.
AB  - VPA daily dose and total VPA concentrations for 146 elderly (> or =65 years)
      nursing home residents collected from June 1998 to December 2000 in homes located
      throughout the United States are presented. Average age was 78.5+/-8.0 years old.
      The mean VPA daily dose was 16.2+/-11.2mg/kg and mean total VPA concentration was
      48.5+/-24.8 mg/L. The majority (56.2%) of the VPA residents are being maintained
      at total VPA levels <50mg/L. Mean daily dose (19.4+/-11.4, 16.3+/-12.1, and
      11.3+/-7.6 mg/kg/day; p=0.003) and total VPA concentration (56.4+/-25.8, 47.7+/
      22.6, and 38.7+/-23.1mg/kg/day; p=0.003) decreased by age groups (65-74, 75-84,
      and > or =85 years). Daily dose and total VPA concentration were not different in
      residents receiving inhibitory or inducing co-medications, between men and women,
      or by albumin level. Total VPA clearance was similar between men and women, among
      age groups, or according to inducing or inhibiting co-medications.

PMID- 15579304
TI  - Genetic liability to epilepsy in Kerala State, India.
AB  - BACKGROUND: Familial clustering is common in epilepsies, but pedigree patterns
      suggest a multi-factorial inheritance. Genetic liability for multi-factorial
      inheritance is population specific and such data are not available for the
      population of Kerala or other states in south India. OBJECTIVES: In this study,
      we have attempted to determine the genetic liability to epilepsy based on an
      adult population of this state. MATERIAL AND METHODS: Pedigrees were recorded for
      probands who reported to the Kerala Registry of Epilepsy and Pregnancy. In order
      to obtain a genetically matched sample for comparison and estimation of empiric
      risks, we have used the family history of the spouse except when the spouse was
      proband's relative. The ILAE criteria were followed for diagnosis and
      classification of epilepsy. RESULTS: Data were collected on 18,419 family members
      of 505 probands with epilepsy (82 men and 423 women) and 10,231 family members of
      spouses (control). The frequency of epilepsy in first and second-degree relatives
      of the spouses was comparable to the population frequency (0.5%), justifying the
      use of this sample as control. Positive family history was observed in 22.2% of
      probands and 8.24% of controls (Odd's Ratio 3.2, 95% Confidence Interval 2.12
      4.73). An affected first-degree relative was observed in 7.5% of probands. The
      corresponding figure for GE, LRE and other epileptic syndromes were 10.2%, 5.8%
      and 5.12%, respectively. The segregation ratio for Juvenile Myoclonic Epilepsy
      (JME) (1:19) was higher than that for other types of Generalized Epilepsy (GE)
      (1:24) and Localization Related Epilepsy (LRE) (1:52). Prevalence of epilepsy
      among the first-degree relatives (1.96%) was greater than the square root of the
      population frequency (0.51%) and was higher than that for second-degree (1.24%)
      and third-degree (0.64%) relatives for the probands. Probands had higher parental
      consanguinity (13.07%) compared to controls (6.64%). The above factors support a
      complex inheritance. Genetic liability to epilepsy (heritability) is greater for
      GE (0.6) and significantly higher for JME (0.7) compared to LRE (0.4). A
      limitation of this study is that the inferences are based on a predominantly
      adult female proband sample but no gender specific differences were identified.
      CONCLUSIONS: The observations of this study indicate complex inheritance and the
      liability values are useful for genetic counseling in the local population.
      Further studies involving more individuals from younger age group and male gender
      are envisaged.

PMID- 15579305
TI  - Cortical laminar disorganization is correlated with severity of the cortical
      dysplasia and surgical outcome--experience with 150 cases.
AB  - The aim of this study is to evaluate that the cortical laminar disorganization
      (CLD) and its correlation with the severity of the cortical dysplasia (CD) and
      surgical outcome. The cohort consists of 150 patients (101 males and 49 females)
      who underwent surgical resection of the epileptic area due to medically
      intractable epilepsy. Histologically, the CLD was divided into three grades
      according to the degree of disarrangement of the clear-cut six-layered cortex and
      the pathological features on MAP2 and NeuN immunostaining; normal to mild,
      moderate and severe CLD in 58 (38.7%), 47 (31.3%) and 45 (30.0%) cases,
      respectively. The histopathological grading of CLD had significant correlation
      with severity of CD (p<0.001), number of single heterotopic neurons in white
      matter (p=0.009), presence of neurons in molecular layer (p<0.001), persistent
      subpial granular cells (p=0.017), cytomegalic neurons (p<0.001) and balloon cells
      (p<0.001), and gray-white matter blurring (p<0.001), and had inverse correlation
      with surgical outcome (<0.001). Since statistically correlated with the known
      parameters of CD and surgical outcome, the grading of CLD could be used as
      another histological parameter for CD.

PMID- 15579306
TI  - Propagation of tonic posturing in supplementary motor area (SMA) seizures.
AB  - We analyzed ictal motor symptoms in 10 patients diagnosed to have supplementary
      motor area (SMA) seizures based on ictal encephalographic (EEG) findings and
      ictal clinical semiology. Inclusion criteria were (1) EEG seizure pattern in the
      vertex for the scalp recording or in the area over and/or adjacent to SMA for
      epicortical recording and (2) ictal motor semiology characterized, as previously
      reported, by sudden and a brief tonic posturing of extremities and trunk mainly
      occurring during sleep without loss of consciousness. In 50% (5/10) of the
      patients, tonic posturing began in one part of the body and moved to other
      part(s) in 5-10s. Unlike Jacksonian march seen in seizures involving the primary
      sensorimotor area (S1-M1), it spread in no accordance with the somatotopy in S1
      M1. The sequential propagation of tonic posturing may represent the somatotopic
      organization within the SMA proper.

PMID- 15579307
TI  - Cortical and limbic excitability in rats with absence epilepsy.
AB  - The classical cortico-reticular theory on absence epilepsy suggests that a
      hyperexcitable cortex is a precondition for the occurrence of absence seizures.
      In the present experiment seizure thresholds and characteristics of cortical and
      limbic epileptic afterdischarges (AD) were determined in a comparative cortical
      stimulation study in young and old adult genetically epileptic WAG/Rij, congenic
      ACI and Wistar rats. Fifteen-second series of 8Hz stimulation of the sensory
      motor cortex were applied in 80- and 180-day-old rats with implanted electrodes.
      Strain differences were found for the threshold for movements directly induced by
      stimulation, low frequency spike-and-wave AD, maximal clonic intensity of
      seizures accompanying direct stimulation, and frequency characteristics of low
      frequency AD. None of these results agreed with a higher cortical excitability
      exclusively in WAG/Rij rats. However, WAG/Rij rats had the longest duration of
      the low frequency AD, and the lowest threshold for the transition to the limbic
      type of AD. The decrease of this threshold correlated with the increase of the
      incidence and total duration of spontaneous SWDs in WAG/Rij rats. It is concluded
      that the elevated excitability of the limbic system or pathways mediating the
      spread of the epileptic activity into this system can be attributed to the
      development of genetic epileptic phenotype in WAG/Rij rats.

PMID- 15579308
TI  - From the Editors' desk.

PMID- 15579309
TI  - Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia
      and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient
      mice.
AB  - Fibroblast growth factor-23 (FGF-23), a recently identified molecule that is
      mutated in patients with autosomal dominant hypophosphatemic rickets (ADHR),
      appears to be involved in the regulation of phosphate homeostasis. Although
      increased levels of circulating FGF-23 were detected in patients with different
      phosphate-wasting disorders such as oncogenic osteomalacia (OOM) and X-linked
      hypophosphatemia (XLH), it is not yet clear whether FGF-23 is directly
      responsible for the abnormal regulation of mineral ion homeostasis and
      consequently bone development. To address some of these unresolved questions, we
      generated a mouse model, in which the entire Fgf-23 gene was replaced with the
      lacZ gene. Fgf-23 null (Fgf-23-/-) mice showed signs of growth retardation by day
      17, developed severe hyperphosphatemia with elevated serum 1,25(OH)2D3 levels,
      and died by 13 weeks of age. Hyperphosphatemia in Fgf-23-/- mice was accompanied
      by skeletal abnormalities, as demonstrated by histological, molecular, and
      various other morphometric analyses. Fgf-23-/-) mice had increased total-body
      bone mineral content (BMC) but decreased bone mineral density (BMD) of the limbs.
      Overall, Fgf-23-/- mice exhibited increased mineralization, but also accumulation
      of unmineralized osteoid leading to marked limb deformities. Moreover, Fgf-23-/-
      mice showed excessive mineralization in soft tissues, including heart and kidney.
      To further expand our understanding regarding the role of Fgf-23 in phosphate
      homeostasis and skeletal mineralization, we crossed Fgf-23-/- animals with Hyp
      mice, the murine equivalent of XLH. Interestingly, Hyp males lacking both Fgf-23
      alleles were indistinguishable from Fgf-23/-/ mice, both in terms of serum
      phosphate levels and skeletal changes, suggesting that Fgf-23 is upstream of the
      phosphate regulating gene with homologies to endopeptidases on the X chromosome
      (Phex) and that the increased plasma Fgf-23 levels in Hyp mice (and in XLH
      patients) may be at least partially responsible for the phosphate imbalance in
      this disorder.

PMID- 15579310
TI  - Cell-type specific trafficking of expressed mutant COMP in a cell culture model
      for PSACH.
AB  - Pseudoachondroplasia (PSACH) is an autosomal dominant disease that mainly affects
      cartilage, resulting in skeletal dysplasias and early onset osteoarthritis. PSACH
      is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene.
      PSACH chondrocytes accumulate unique COMP-containing lamellar structures in an
      expanded rough endoplasmic reticulum (rER). Although COMP is also present in
      tendon extracellular matrix (ECM), it does not accumulate in PSACH tendon cells,
      suggesting the disease involves a chondrocyte-specific trafficking problem. To
      investigate putative cell-specific trafficking differences, we generated a cell
      culture model utilizing expression of the common DeltaD469 COMP mutation. In rat
      chondrosarcoma (RCS) cells, we find delayed secretion and ER accumulation of
      DeltaD469 COMP, paralleling the altered trafficking defect in PSACH chondrocytes.
      Non-chondrocytic COS-1 cells, in contrast, efficiently trafficked and secreted
      both mutant and wild-type COMP. In chondrocytic cells, expression of DeltaD469
      COMP led to ER accumulation of type IX collagen, but did not affect aggrecan
      trafficking. Endogenous rat COMP accumulated in the ER along with expressed
      DeltaD469 COMP in a stably expressing RCS clone, consistent with the dominant
      negative effect of PSACH. When these stably expressing cells were cultured to
      promote ECM deposition, the small amount of secreted mutant COMP disrupted
      assembly of the normal fibrillar meshwork and caused irregular aggregates of COMP
      and type IX collagen to form. Thus, in a new model that reflects the cellular
      pathology of PSACH, we establish trafficking differences for mutant COMP in
      chondrocytic and non-chondrocytic cells and demonstrate that mutant COMP
      interferes with assembly of a normal ECM.

PMID- 15579311
TI  - Collagen, type V, alpha1 (COL5A1) is regulated by TGF-beta in osteoblasts.
AB  - Bone matrix contains high concentrations of growth factors that are known to play
      important regulatory roles during osteogenesis, particularly transforming growth
      factor-beta (TGF-beta). Divergent effects of TGF-beta on bone formation have been
      reported both in vitro and in vivo depending upon experimental conditions, cells
      employed and their stage of maturation. In this study, we have used a clonal
      osteoblastic cell line MC3T3-E1, derived from newborn mouse calvaria, as an in
      vitro model of bone development. These cells undergo an ordered, time-dependent
      developmental sequence characterized by three stages (proliferation,
      differentiation and mineralization), over a 30-35-day period. In this study, cDNA
      microarray technology was used to study the expression profile of 8470 genes, in
      the presence of TGF-beta1 during osteoblast development. Microarray analysis
      revealed 120 cDNAs to be differentially expressed in MC3T3-E1 osteoblasts that
      had been treated with TGF-beta1. From the 120 differentially expressed genes, we
      selected Collagen, type V, alpha1 (COL5A1) {differential expression=+4.9} for
      further studies since it represents a previously uncharacterized component of the
      bone matrix. Using Northern blotting, we found that, when MC3T3-E1 cells were
      treated with TGF-beta1, COL5A1 was up-regulated during the proliferation and
      differentiation phases of osteogenesis. Furthermore, by a combination of RNA in
      situ hybridization and Northern blotting, we found COL5A1 mRNA to be expressed in
      the calvaria and developing bone of the E17.5 mouse embryos. Lastly, significant
      COL5A1 protein expression was observed by immunohistochemistry in the developing
      bone of the E17.5 mouse embryos. In conclusion, by the use of in vitro and in
      vivo approaches, we have discovered that the COL5A1 gene is a target of TGF-beta
      during osteogenesis.

PMID- 15579312
TI  - Expression and characterization of recombinant osteopontin peptides representing
      matrix metalloproteinase proteolytic fragments.
AB  - Osteopontin (OPN) is a secreted, arginine-glycine-aspartic acid (RGD)-containing
      phosphoprotein proteolytically modified by members of the matrix
      metalloproteinase (MMP) family. We previously defined the MMP-3 and MMP-7
      cleavage sites in OPN and found increased adhesive and migratory activity of a
      pool of MMP-cleaved fragments compared to full-length OPN. In the present study,
      we performed mutational analysis of recombinant full-length OPN and generated
      recombinant OPN fragments corresponding to the MMP-cleaved fragments, which have
      apparent molecular weights of 40, 32, and 25 kD by SDS-PAGE. Single residue
      mutations in 167L and 211L do not abrogate MMP cleavage although processing of
      the putative C-terminal fragment appears to be affected by a 167L to 167A
      mutation. The N-terminal 40-kD fragment was a stronger adhesive substrate
      compared to full-length OPN despite the observation that full-length OPN
      displayed greater binding in soluble phase to endothelial cell surfaces. While
      the 32-kD fragment showed significant binding to endothelial cell surfaces, the C
      terminal 25-kD fragment did not interact with cell surface. Our data indicate
      that the increased adhesive activity of MMP-cleaved OPN was accountable by the N
      terminal 40-kD fragment. We further analyzed receptor binding, using competition
      with peptides representing the alpha4beta1 and alpha9beta1 binding sites in the
      40-kD N-terminal fragment. Using Jurkat cells, we found that a peptide
      corresponding to 131ELVTDFPTDLPATE144 had no effect on cell adhesion, whereas the
      peptide SVVYGLR competitively inhibited cell adhesion. These results suggest that
      a shorter motif that is found in MMP-cleaved OPN, 162SVVYG166, is sufficient to
      mediate cell adhesion of Jurkat cells to receptors, including the beta1
      integrins, which have been previously characterized to bind the SVVYGLR sequence.

PMID- 15579313
TI  - Do changes in the mechanical properties of articular cartilage promote catabolic
      destruction of cartilage and osteoarthritis?
AB  - Osteoarthritis (OA) is a joint disease characterized by cartilage degeneration, a
      thickening of subchondral bone, and formation of marginal osteophytes. Previous
      mechanical characterization of cartilage in our laboratory suggests that energy
      storage and dissipation is reduced in osteoarthritis as the extent of
      fibrillation and fissure formation increases. It is not clear whether the loss of
      energy storage and dissipation characteristics is a result of biochemical and/or
      biophysical changes that occur to hyaline cartilage in joints. The purpose of
      this study is to present data, on the strain rate dependence of the elastic and
      viscous behaviors of cartilage, in order to further characterize changes that
      occur in the mechanical properties that are associated with OA. We have
      previously hypothesized that the changes seen in the mechanical properties of
      cartilage may be due to altered mechanochemical transduction by chondrocytes.
      Results of incremental tensile stress-strain tests at strain rates between
      100%/min and 10,000%/min conducted on OA cartilage indicate that the slope of the
      elastic stress-strain curve increases with increasing strain rate, unlike the
      reported behavior of skin and self-assembled collagen fibers. It is suggested
      that the strain-rate dependence of the elastic stress-strain curve is due to the
      presence of large quantities of proteoglycans (PGs), which protect articular
      cartilage by increasing the apparent stiffness. The increased apparent stiffness
      of articular cartilage at high strain rates may limit the stresses borne and
      prolong the onset of OA. It is further hypothesized that increased compressive
      loading of chondrocytes in the intermediate zone of articular cartilage occurs as
      a result of normal wear to the superficial zone or from excessive impact loading.
      Once the superficial zone of articular cartilage is worn away, the tension is
      decreased throughout all cartilage zones leading to increased chondrocyte
      compressive loading and up-regulation of mechanochemical transduction processes
      that elaborate catabolic enzymes.

PMID- 15579314
TI  - Basement membrane protein and matrix metalloproteinase deregulation in engineered
      human oral mucosa following infection with Candida albicans.
AB  - A variety of morphological changes in the basement membrane (BM) are known to
      occur in inflammatory diseases. Modifications of the BM can be associated with
      significant changes in protein content. Candida albicans (C. albicans) is
      normally a commensal organism and is a member of the natural flora of a large
      number of healthy individuals. However, under certain conditions, C. albicans can
      invade host tissues, causing inflammation and tissue damage. The aim of this
      study was to investigate the effect of C. albicans on the expression and
      production of structural (laminin-5 and type IV collagen) and inflammatory
      [matrix metalloproteinases (MMPs) and their inhibitors] proteins by human oral
      epithelial cells. Using engineered normal human oral mucosa infected with 10(5)
      C. albicans/cm2 for different periods of time, we were able to demonstrate that
      this yeast promotes significant laminin-5 and type IV collagen gene activation
      and protein secretion. These effects were accompanied by MMP-2 and MMP-9 gene
      activation. Interestingly, only the levels of active MMP-9 rose. The increase in
      MMP levels was paralleled by a decrease in the secretion of type 2 matrix
      metalloproteinase tissue inhibitors (TIMP-2). Our results demonstrated that C.
      albicans has a significant effect on tissue structure through BM protein and MMP
      modulation. This might help C. albicans overcome the mechanical and biological
      defenses of the tissue and allow it to disseminate, causing severe infections. If
      C. albicans uses MMPs (mainly MMP-9) to disseminate, inhibition of this protease
      could be of interest in treating a variety of inflammatory disorders, including
      oral candidiasis.

PMID- 15579315
TI  - Genomic organization and sequence variation of the human integrin subunit alpha8
      gene (ITGA8).
AB  - The integrin alpha8 is highly expressed during kidney and lung development.
      alpha8-deficient mice display abnormal renal development suggesting that alpha8
      plays a critical role in organogenesis. Therefore, it would be of considerable
      interest to understand the genomic structure, localization and sequence variation
      of the alpha8 gene. Using FISH and genomic database analysis, we show that alpha8
      gene maps to chromosome 10p13 and consists of >200 kbp organized into 30 exons.
      Examination of 47 individuals from two different ethnic groups (European and
      African descent) identified 286 varying sites. The diversity of alpha8 is
      comparable to that of other regions within the human genome. Eight of the varying
      sites were located in the coding regions: six resulted in nonsynonymous
      substitutions of which two lead to non-conservative changes in protein. None of
      the sites showed significant deviation from Hardy-Weinberg equilibrium. We mapped
      the coding region single nucleotide polymorphisms (SNPs) onto a model of the
      predicted alpha8 structure and found all the SNPs were located in the "calf" of
      the extracellular domain. In the European population, the linkage disequilibrium
      statistic D' showed three blocks of relatively non-recombinant regions in the
      alpha8 gene while the African population showed more evidence of recombination.
      The observed patterns of the linkage disequilibrium statistic R2 suggest that a
      large number of sites will need to be genotyped to ensure coverage of the entire
      gene for genetic association studies. Identification of the sequence variation
      will allow genetic association studies of alpha8 in kidney and lung disease.

PMID- 15579316
TI  - Variations in UV-B tolerance and germination speed of Metarhizium anisopliae
      conidia produced on insects and artificial substrates.
AB  - Solar ultraviolet radiation (UV-A and UV-B) is a major factor in failure of
      programs using the insect pathogenic fungus Metarhizium anisopliae as a
      biological control agent. Studies were conducted to determine if growth
      conditions, viz. artificial (agar media or rice grain) or natural (infected
      insects) substrates for conidial production affect two traits that directly
      influence performance of conidia after field application: tolerance to UV-B
      radiation and conidial germination speed. Conidia of two isolates (ARSEF 23 and
      ARSEF 2575) of M. anisopliae var. anisopliae produced on potato dextrose agar
      plus yeast extract (PDAY) or on fungus-killed larvae of two insect species,
      Galleria mellonella and Zophobas morio, were inactivated by exposure to UV-B
      radiation. Conidia of both isolates when produced on insect cadavers were
      significantly more sensitive to UV-B radiation than conidia produced on PDAY.
      Also, conidia from insect cadavers germinated slower than those from PDAY
      cultures. A comparison of conidia from artificial substrates showed that conidia
      produced on Czapek's and Emerson's YpSs agar media or rice grains had higher
      tolerance to UV-B radiation and germinated faster than conidia raised on PDA and
      PDAY. Accordingly, the growth substrate and nutritional environment in which
      conidia are produced influences M. anisopliae conidial UV-B tolerance and speed
      of germination; and manipulation of these variables could be used to obtain
      conidia with increased tolerance to UV-B radiation and shorter germination times.

PMID- 15579317
TI  - Multiple virus infections in the honey bee and genome divergence of honey bee
      viruses.
AB  - Using uniplex RT-PCR we screened honey bee colonies for the presence of several
      bee viruses, including black queen cell virus (BQCV), deformed wing virus (DWV),
      Kashmir bee virus (KBV), and sacbrood virus (SBV), and described the detection of
      mixed virus infections in bees from these colonies. We report for the first time
      that individual bees can harbor four viruses simultaneously. We also developed a
      multiplex RT-PCR assay for the simultaneous detection of multiple bee viruses.
      The feasibility and specificity of the multiplex RT-PCR assay suggests that this
      assay is an effective tool for simultaneous examination of mixed virus infections
      in bee colonies and would be useful for the diagnosis and surveillance of honey
      bee viral diseases in the field and laboratory. Phylogenetic analysis of putative
      helicase and RNA-dependent RNA polymerase (RdRp) encoded by viruses reveal that
      DWV and SBV fall into a same clade, whereas KBV and BQCV belong to a distinct
      lineage with other picorna-like viruses that infect plants, insects and
      vertebrates. Results from field surveys of these viruses indicate that mixed
      infections of BQCV, DWV, KBV, and SBV in the honey bee probably arise due to
      broad geographic distribution of viruses.

PMID- 15579318
TI  - Influence of temperature preferences of two Paecilomyces fumosoroseus lineages on
      their co-infection pattern.
AB  - In order to clarify the epidemiological potential of entomopathogenic fungi for
      insect pest control, the role of the temperature as one environmental constraint
      was investigated on the pattern of co-infection of Galleria mellonella by two
      distinct lineages of a hyphomycete, Paecilomyces fumosoroseus. The distribution
      of conidial populations collected on cadavers of hosts co-infected under 20
      regimes, ranging from 13 to 35 degrees C, was examined. The apparent temperature
      tolerance of both fungal isolates was related to their in vitro colony growth and
      their in vivo sporulation ability. The conidial populations were characterized by
      molecular markers based on restriction fragment length polymorphisms of the
      internal transcribed spacers (ITS-RFLP) and random amplified polymorphic DNA
      (RAPD) contrasting profiles in combination with the conidial size. This study
      allowed a different temperature profile was identified for each isolate. Under
      most temperature regimes, only one lineage prevailed upon the infected insect;
      whereas both lineages coexisted at 20-25 and 25-25 degrees C. When one haplotype
      dominated, the displacement of the other one depended on its temperature
      tolerance. These results suggest that more consideration should be given to
      population-genetics analyses for evaluating the adaptability of microbial control
      agents to targeted environments.

PMID- 15579319
TI  - Studies on the impact of two Nosema isolates from Bulgaria on the gypsy moth
      (Lymantria dispar L.).
AB  - We investigated host-parasite interactions of two Nosema-type microsporidian
      isolates recovered from populations of Lymantria dispar L. in northwestern
      Bulgaria, one near Veslec and one near Levishte. Bioassay studies produced
      information on development, stage specific mortality, pupation, and adult
      eclosion of infected individuals. Horizontal transmission of the two isolates was
      investigated in a second set of experiments. At dosages ranging from 2 x 10(2) to
      5 x 10(4) spores/microl, the infection rates varied between 77 and 100% for the
      isolate from Veslec and between 92 and 99% for the Levishte isolate. The Veslec
      isolate caused a slightly higher mortality rate and the median time to death was
      shorter compared to the isolate from Levishte. The total mortality for both
      isolates varied between 79 and 99%, independent of spore dosages. A lower
      relative growth rate was recorded for male and female L. dispar larvae infected
      with either isolate during the third larval instar and a higher relative growth
      rate during the fourth instar compared to the control groups. Pupal weight did
      not differ significantly among females, but male infected pupae were heavier than
      the controls. Nosema sp. [Veslec] was as efficiently transmitted as Nosema sp.
      [Levishte]; 42% of the susceptible larvae became infected with the Veslec isolate
      when uninfected larvae were exposed to infected larvae; 43% of larvae became
      infected with the Nosema sp. [Levishte]. The latency period varied between 7 and
      8 days for both isolates.

PMID- 15579320
TI  - Insect cellular and chemical limitations to pathogen development: the Colorado
      potato beetle, the nematode Heterorhabditis marelatus, and its symbiotic
      bacteria.
AB  - This research examines possible factors limiting pathogen development and
      reproduction in a novel host insect. The nematode Heterorhabditis marelatus and
      its symbiotic bacterium, Photorhabdus luminescens, kill 98% of nematode-treated
      Colorado potato beetle (CPB) prepupae, but the nematode reproduces in only 1-6%
      of beetles. We examined nematode/bacterial inhibition at each step of the normal
      developmental pathway to determine host feature(s) limiting nematode
      reproduction. We found that in vivo encapsulation of nematodes occurred in only
      1.6% of CPB, and in 5% of in vitro hanging drops of hemolymph. Thus, the cellular
      defense system did not strongly limit nematode reproduction in the CPB. The
      symbiotic bacterium was negatively affected by a heat-labile factor found in the
      CPB's hemolymph which often caused the bacterium to switch from the primary form
      that produces antibiotics and nutrients necessary for the nematodes' development,
      to a secondary form that provides only limited nutrients. A 58 kDa protein was
      isolated and bioassayed for activity against P. luminescens, but caused a delay
      in bacterial growth rather than the primary-secondary form switch. Thus, the
      identity of the heat-labile factor could not be confirmed as being the 58 kDa
      protein. The heat-labile factor did not directly affect the nematode. The
      addition of lipids in the form of olive oil to heated CPB hemolymph allowed
      nematodes to reproduce in 17% of hanging drops, in contrast to zero reproduction
      in hemolymph without oil. Reproductive nematodes were smaller when grown in CPB
      hemolymph than in hemolymph of the highly susceptible Galleria mellonella. These
      data suggest that both the toxic heat-labile factor and a lack of appropriate
      nutrients alter the CPB-bacterium-nematode interaction. These factors preclude
      the use of this otherwise highly effective nematode-bacterial complex in the
      longterm control of the CPB.

PMID- 15579321
TI  - Leishmania parasites (Kinetoplastida: Trypanosomatidae) reversibly inhibit
      visceral muscle contractions in hemimetabolous and holometabolous insects.
AB  - Female sand flies can acquire protozoan parasites in the genus Leishmania when
      feeding on an infected vertebrate host. The parasites complete a complex growth
      cycle in the sand fly gut until they are transmitted by bite to another host.
      Recently, a myoinhibitory peptide was isolated from Leishmania major
      promastigotes. This peptide caused significant gut distension and reversible,
      dose-dependent inhibition of spontaneous hindgut contractions in the enzootic
      sand fly vector, Phlebotomus papatasi. The current study further characterizes
      myoinhibitory activity in L. major and other kinetoplastid parasites, using the
      P. papatasi hindgut and other insect organ preparations. Myoinhibitory activity
      was greatest in cultured promastigotes and in culture medium in late log-phase
      and early stationary-phase, coinciding with development of infective Leishmania
      morphotypes in the sand fly midgut. L. major promastigote lysates inhibited
      spontaneous contractions of visceral muscle preparations from hemimetabolous
      (Blattaria and Hemiptera) and holometabolous (Diptera) insects. Inhibition of
      visceral muscle contractions in three insect orders indicates a conserved mode of
      action. Myoinhibitory activity was detected also in Leishmania braziliensis
      braziliensis, a Sudanese strain of Leishmania donovani, and the kinetoplastid
      parasite Leptomonas seymouri. Protozoan-induced myoinhibition mimics the effect
      of insect myotropins. Inhibiting host gut contractions protects Leishmania
      parasites from being excreted after blood meal and peritrophic matrix digestion,
      allowing development and transmission of infective forms.

PMID- 15579322
TI  - The development of the endoparasitoid Venturia canescens in Bt-tolerant, immune
      induced larvae of the flour moth Ephestia kuehniella.
AB  - We examined the survival and development of the endoparasitoid Venturia canescens
      in a Bt-tolerant laboratory strain of the flour moth Ephestia kuehniella, in
      which Bt-tolerance has been shown to be associated with an inducible elevation of
      the insect's immune response. The results indicate the elevated immune status
      associated with Bt-tolerance does not confer cross-protection against parasitism
      by V. canescens. No significant difference was observed in the rate of emergent
      wasps from parasitised Bt-tolerant and Bt-susceptible hosts. In addition, wasps
      from Bt-tolerant hosts had longer development times and were larger than wasps
      from Bt-susceptible hosts.

PMID- 15579323
TI  - In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid
      analogues.
AB  - Brassinosteroids are a novel group of steroids that appear to be ubiquitous in
      plants and are essential for normal plant growth and development. It has been
      previously reported that brassinosteroid analogues exert an antiviral activity
      against herpes simplex virus type 1 (HSV-1) and arenaviruses. In the present
      study, we report the chemical synthesis of compounds (22S,23S)-3beta-bromo
      5alpha,22,23-trihydroxystigmastan-6-one (2), (22S,23S)-5alpha-fluoro-3beta-22,23
      trihydroxystigmastan-6-one (3), (22S,23S)-3beta,5alpha,22,23-tetrahydroxy
      stigmastan-6-one (4) as well as their antiherpetic activity both in a human
      conjunctive cell line (IOBA-NHC) and in the murine herpetic stromal keratitis
      (HSK) experimental model. All compounds prevented HSV-1 multiplication in NHC
      cells in a dose dependent manner when added after infection with no cytotoxicity.
      Administration of compounds 2, 3, and 4 to the eyes of mice at 1, 2, and 3 days
      post-infection delayed and reduced the incidence of HSK, consisting mainly of
      inflammation, vascularization, and necrosis, compared to untreated, infected
      mice. However, viral titers of eye washes showed no differences among samples
      from treated and untreated mice. Since the decrease in the percentage of mice
      with ocular lesions occurred 5 days after treatment had ended, we suggest that
      brassinosteroids 2, 3, and 4 did not exert a direct antiviral effect in vivo, but
      rather may play a role in immune-mediated stromal inflammation, which would
      explain the improvement of the clinical signs of HSK observed.

PMID- 15579324
TI  - Simultaneous determination of steroid composition of human testicular fluid using
      liquid chromatography tandem mass spectrometry.
AB  - A rapid, sensitive, and specific method using liquid chromatography tandem mass
      spectrometry (LC/MS/MS) has been developed for simultaneous determination of
      testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and 5alpha-androstan
      3alpha, -17beta-diol (3alpha-Diol) within human testicular fluid. Sample
      pretreatment involved a one-step extraction with diethyl ether. The analytes were
      separated on a Waters X-Terra C18 (150 mm x 2.1 mm i.d., 3.5 microm) analytical
      column with acetonitrile/water mobile phase (70:30, v/v) containing 0.1% formic
      acid using isocratic flow at 0.15 ml/min for 8 min. The column effluent was
      monitored by tandem mass spectrometry with electrospray positive ionization.
      Linear calibration curves were generated over the range of 0.1-50 ng/ml for T,
      0.02-1 ng/ml for DHT, 0.05-2 ng/ml for E2, and 0.2-10 ng/ml for 3alpha-Diol, with
      values for the coefficient of determination of >0.99. The overall extraction
      efficiency was greater than 86% for T, 75% for DHT, 66% for E2, and 60% for
      3alpha-Diol. The values for within-day and between-day precision and accuracy
      were <15%. We measured each of the four steroids in testicular sample volumes of
      only 20 microl, obtained by percutaneous testicular aspiration. The mean
      intratesticular testosterone concentration found by LC/MS/MS, 572 +/- 102 ng/ml,
      was similar to that previously obtained by radioimmunoassay (RIA). The mean
      intratesticular estradiol concentration was 15.7 +/- 2.3 ng/ml, which also
      correlated well with RIA measurement. Both DHT and 3alpha-Diol were below the
      limits of detection by RIA, but could be measured accurately by LC/MS/MS. In
      conclusion, LC/MS/MS represents a sensitive and accurate means by which to
      measure four separate steroids within small volume samples of testicular fluid.

PMID- 15579325
TI  - Plant 2-arylobenzofurans demonstrate a selective estrogen receptor modulator
      profile.
AB  - We have isolated from the plant Onobrychis ebenoides three novel arylobenzofurans
      with binding affinity for the estrogen receptor. In this study, we evaluated
      these arylobenzofurans, namely ebenfuran I, ebenfuran II and ebenfuran III for
      their potential selective estrogen receptor modulator (SERM)-like properties. We
      examined their ability, (1) to induce the insulin growth factor binding protein-3
      (IGFBP-3) in MCF-7 breast cancer cells, (2) to stimulate differentiation and
      mineralization of osteoblastic cell culture by histochemical staining for
      alkaline phosphatase, Alizarin Red-S staining and calcium levels in the
      supernatants and (3) to inhibit cell proliferation of cervical adenocarcinoma
      (Hela) cells by use of the MTT assay. An estrogen receptor mediated effect was
      investigated by carrying out chloramphenicol acetyl transferase (CAT) assay on
      transient MCF-7 transfectants. Estradiol and the "pure" antiestrogen ICI 182780
      were included to serve as control samples of the estrogenic and antiestrogenic
      effect respectively. Our data reveal that ebenfuran II is a highly potent SERM,
      exhibiting antiestrogenic activity in breast cancer cells via the estrogen
      receptor, estrogenic effect on osteoblasts and no stimulatory effect on cervix
      adenocarcinoma cells. In conclusion, our study is the first to demonstrate that
      plant derived arylobenzofurans show a SERM profile and may be considered for the
      prevention and treatment of diseases such as breast cancer, cervical cancer and
      osteoporosis.

PMID- 15579326
TI  - Secosteroids of marine origin.
AB  - This review describes the isolation from marine organisms of all secosteroids
      reported in the literature from 1972 to 2004. Secosteroids are highly oxidized
      metabolites with bond cleavage in the rings of the steroid tetracyclic nucleus.
      All secosteroids are grouped in accordance with their ring joined to side chain
      as 5,6-, 9,11-, 9,10- 8,9-, 8,14- and 13,17-secosteroids and the structures and
      the synthetic works, where available, are reported. Furthermore, this review
      gives details on the biological activities of the isolated secosteroids (e.g.
      antiproliferative, antifouling, antiinflammatory, antimicrobial, ichthyotoxic and
      antiviral).

PMID- 15579327
TI  - Low-calcemic, efficacious, 1alpha,25-dihydroxyvitamin D3 analog QW-1624F2-2:
      calcemic dose-response determination, preclinical genotoxicity testing, and
      revision of A-ring stereochemistry.
AB  - Based on an X-ray crystal structure determination, the A-ring stereochemistry of
      hybrid analog QW-1624F2-2 (1alpha-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy
      26,27-bis-homovitamin D3) is revised to be 1alpha-CH2OH-3beta-OH. This analog is
      shown to be approximately 80-100 times less calciuric than the natural hormone
      1alpha,25-dihydoxyvitamin D3. This analog is shown also to be non-genotoxic in
      three different standard assays.

PMID- 15579328
TI  - Licorice reduces serum testosterone in healthy women.
AB  - Licorice has been considered a medicinal plant for thousands of years. The most
      common side effect is hypokalemic hypertension, which is secondary to a block of
      11beta-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to
      an enhanced mineralocorticoid effect of cortisol. We have investigated the effect
      of licorice on androgen metabolism in nine healthy women 22-26 years old, in the
      luteal phase of the cycle. They were given 3.5 g of a commercial preparation of
      licorice (containing 7.6% W.W. of glycyrrhizic acid) daily for two cycles. They
      were not on any other treatment. Plasma renin activity, serum adrenal and gonadal
      androgens, aldosterone, and cortisol were measured by radioimmunoassay. Total
      serum testosterone decreased from 27.8+/-8.2 to 19.0+/-9.4 in the first month and
      to 17.5+/-6.4 ng/dL in the second month of therapy (p<0.05). It returned to pre
      treatment levels after discontinuation. Androstenedione, 17OH-progesterone, and
      LH levels did not change significantly during treatment. Plasma renin activity
      and aldosterone were depressed during therapy, while blood pressure and cortisol
      remained unchanged. CONCLUSIONS: Licorice can reduce serum testosterone probably
      due to the block of 17-hydroxysteroid dehydrogenase and 17-20 lyase. Licorice
      could be considered an adjuvant therapy of hirsutism and polycystic ovary
      syndrome.

PMID- 15579329
TI  - Intracellular Ca2+ stimulates the binding to androgen receptors in platelets.
AB  - In this study, we demonstrated that ADP-induced platelet aggregation activates
      the binding of testosterone (T) to its receptor. It is well known that binding of
      ADP to its receptors induced the release of Ca2+ ions from dense bodies into the
      cytosol of platelets. In this work, we compared the binding of testosterone or
      dihydrotestosterone to their receptors using cytosol obtained from ADP-treated
      and non-treated platelets. These experiments were repeated using EGTA (a calcium
      chelator) or U73122 (a phospholipase C enzymatic activity inhibitor) to the ADP
      treated platelets. In addition, we also developed a competition analysis for the
      androgen receptors (AR) using [3H]DHT, non-radioactive T, DHT or cyproterone
      acetate from ADP-treated platelets cytosol. The results from this study indicate
      that the cytosol obtained from non-ADP-treated platelets did not show any binding
      to [3H]T or [3H]DHT, whereas cytosol from ADP-treated platelets binds to the
      radio-labeled androgens. Furthermore cytosol from ADP plus U73122-treated
      platelets did not show binding to [3H]T or [3H]DHT. These data suggest that
      intracellular Ca2+ ions stimulates the binding of androgens to their receptors in
      platelets cytosol. The competition analysis shows that T and DHT have high
      affinities for the androgen receptors with similar IC50 values, whereas
      cyproterone acetate shows a lower affinity. The results from these data clearly
      indicate the presence of androgen receptors in platelets.

PMID- 15579330
TI  - Gas chromatographic-mass spectrometric identification of 16alpha-hydroxy
      dehydroepiandrosterone in human seminal plasma.
AB  - 16alpha-hydroxydehydroepiandrosterone was for the first time detected in human
      seminal plasma by using a combination of extraction, solvent partition, HPLC
      separation and final quantification by GC-MS as pentafluorobenzyloxime
      trimethylsilyl ether derivative in SIM mode. Three effective mass fragments m/z
      266, 356 and 446 were followed. The concentration of 16alpha
      hydroxydehydroepiandrosterone amounted in average 1.06 nmol/l, being lower but
      close to- the product of concurrent DHEA metabolism, 7
      hydroxydehydroepiandrosterone isomers, found recently in seminal plasma.

PMID- 15579331
TI  - Strategies for two-stage sampling designs for estimating herd-level prevalence.
AB  - We propose a herd-level sample-size formula based on a common adjustment for
      prevalence estimates when diagnostic tests are imperfect. The formula depends on
      estimates of herd-level sensitivity and specificity. With Monte Carlo
      simulations, we explored the effects of different intracluster correlations on
      herd-level sensitivity and specificity. At low prevalence (e.g. 1% of animals
      infected), herd-level sensitivity increased with increasing intracluster
      correlation and many herds were classified as positive based only on false
      positive test results. Herd-level sensitivity was less affected at higher
      prevalence (e.g. 20% of animals infected). A real-life example was developed for
      estimating ovine progressive pneumonia prevalence in sheep. The approach allows
      researchers to balance the number of herds and the total number of animals
      sampled by manipulating herd-level test characteristics (such as the number of
      animals sampled within a herd).

PMID- 15579332
TI  - Age-period-cohort analysis of the Bovine Spongiform Encephalopathy (BSE) epidemic
      in Switzerland.
AB  - Cattle born after animal-feed control measures were implemented in 1990 have
      become BSE cases in Switzerland, indicating sub-optimal effectiveness of these
      measures. To evaluate these measures, the incidence of BSE cases in Switzerland
      recorded through clinical case reporting from January 1991 to June 2000
      (categorized into age groups and birth cohorts of 6-month duration) was analyzed
      by Poisson log-linear regression using an age-period-cohort model. The incidence
      was maximum in the cattle cohort born from October 1989 to March 1990, and
      dropped to zero in the cohort born from April to September 1991. A second peak
      was observed in a cohort born from April to September 1994. The first drop of
      incidence is interpreted as a result of initial implementation of the feed ban in
      1990. The second peak might be related to exposure of cattle to feed intended for
      pigs and poultry.

PMID- 15579333
TI  - Estimation of the age-dependent risk of infection to BSE of dairy cattle in Great
      Britain.
AB  - An important aspect of the bovine spongiform encephalopathy (BSE) epidemic has
      been an apparent age-dependent risk of infection, with younger cattle being more
      likely to become infected than older cattle. Our objective was to determine the
      age-dependent risk of infection of dairy cattle. We first reviewed unpublished
      data on the feeding patterns of proprietary concentrates for dairy-replacement
      cattle. These data showed that autumn- and spring-born cattle would receive
      different feeding patterns of proprietary concentrates, and so age-dependent risk
      of infection profiles were obtained separately for autumn- and spring-born
      cattle. We used back-calculation methods to analyse BSE-epidemic data collected
      in Great Britain between 1984 and 1996. Dairy cattle were most at risk in the
      first 6 months of life; adult cattle were at relatively low risk of infection.
      Between 6 and 24 months of age, risk profiles reflected feeding patterns of
      proprietary concentrates in each of the autumn- and spring-born cohorts.

PMID- 15579334
TI  - Biosecurity in 116 Danish fattening swineherds: descriptive results and factor
      analysis.
AB  - Biosecurity measures are important for the herd's protection against diseases and
      also to provide nationwide protection against the introduction of exotic
      diseases. In this paper, we describe the farmers' choices and routines regarding
      biosecurity in Danish fattening herds. Overall, 116 Danish swine fattening herds
      in three areas of different pig density were interviewed. Of these herds, 78%
      purchased weaners from one sow herd only, whereas 10% purchased from >5 sow herds
      during 1 year. Large herds (>500 finishers) purchased weaners more often than
      smaller herds (< or =500 finishers). Only two swine producers purchased weaners
      from a market. Almost all herds (95%) received weaners from one sow herd at one
      time, and only one herd received from >5 sow herds in one batch. Twenty-one
      percent did not use an effective barrier between the loading area and the stables
      when delivering pigs for slaughter. Entry rooms (in which clothing and boots are
      changed) were common at the farm, and the numbers of visitors were generally low
      (<10 visitors a year). Factor analysis was performed to find underlying
      structures of the biosecurity measures in the herd; four factors were chosen
      (eigenvalue > 3.10). A site scoring high on factor 1 was a large SPF herd, which
      received weaners from a single source, had biosecurity requirements for the
      transport vehicles, and had a high level of biosecurity for visitors. A site
      scoring high on factor 2 was a multi-site farm, which had personnel working on
      more than one of the sites, only received weaners from one sow herd, had
      delivering herds placed close to the participating site, and transported animals
      themselves. A site scoring high on factor 3 was a site which hired commercial
      transport for slaughter, was situated far from the abattoir and had a high level
      of biosecurity when loading pigs. A production site scoring high on factor 4 was
      a large site, which used all-in/all-out management, washed and disinfected
      between each group, and purchased many weaners.

PMID- 15579335
TI  - Duration of immunity of a quadrivalent vaccine against respiratory diseases
      caused by BHV-1, PI3V, BVDV, and BRSV in experimentally infected calves.
AB  - Several laboratory studies assessed the duration of immunity of a quadrivalent
      vaccine (Rispoval 4, Pfizer Animal Health) against bovine respiratory diseases
      (BRD) caused by bovine herpes-virus type-1 (BHV-1), parainfluenza type-3 virus
      (PI3V), bovine viral-diarrhoea virus type 1 (BVDV), or bovine respiratory
      syncytial virus (BRSV). Calves between 7 weeks and 6 months of age were allocated
      to treatment and then were injected with two doses of either the vaccine or the
      placebo 3 weeks apart. Six to 12 months after the second injection, animals were
      challenged with BHV-1 (n=16), PI3V (n=31), BVDV (n=16), or BRSV (n=20) and the
      course of viral infection was monitored by serological, haematological (in the
      BVDV study only), clinical, and virological means for > or =2 weeks. Infection
      induced mild clinical signs of respiratory disease and elevated rectal
      temperature in both vaccinated and control animals and was followed by a dramatic
      rise in neutralising antibodies in all treatment groups. Titres reached higher
      levels in vaccinated calves than in control calves after challenge with BHV-1,
      BVDV, or BRSV. On day 3 after PI3V challenge, virus shedding was reduced from
      3.64 log10TCID50 in control animals to 2.59 log10TCID50 in vaccinated animals. On
      days 6 and 8 after BRSV challenge, there were fewer vaccinated animals (n=2/10
      and 0/10, respectively) shedding the virus than control animals (n=8/10 and 3/10,
      respectively). Moreover, after challenge, the mean duration of virus shedding was
      reduced from 3.8 days in control animals to 1 day in vaccinated animals in the
      BVDV study and from 3.4 days in control animals to 1.2 days in vaccinated animals
      in the BRSV study. The duration of immunity of >or =6 months for PI3V, BHV-1 and
      BVDV, and 12 months for BRSV, after vaccination with Rispoval 4, was associated
      mainly with enhanced post-challenge antibody response to all four viruses and
      reduction of the amount or duration of virus shedding or both.

PMID- 15579336
TI  - Probability of introduction of exotic strains of bluetongue virus into the US and
      into California through importation of infected cattle.
AB  - Strategies designed to minimize the probability of bluetongue virus (BTV)
      introduction to new areas should be based on a quantitative assessment of the
      probability of actually establishing the virus once it is introduced. The risk of
      introducing a new strain of bluetongue virus into a region depends on the number
      of viremic animals that enter and the competency of local vectors to transmit the
      virus. We used Monte Carlo simulation to model the probability of introducing BTV
      into California, USA, and the US through importation of cattle. Records of cattle
      and calf imports into California and the US were obtained, as was seroprevalence
      information from the exporting countries. A simulation model was constructed to
      evaluate the probability of importing either a viremic PCR-negative animal after
      14-day quarantine, a c-ELISA BTV-antibody-negative animal after 28-day
      quarantine, or an untested viremic animal after 100-day quarantine into
      California and into the US. We found that for animals imported to the US, the
      simulated (best to worst scenarios) median percentage that tested positive for
      BTV-antibody ranged from 5.4 to 7.2%, while for the subset imported to
      California, the simulated median percentage that tested positive for BTV-antibody
      ranged from 20.9 to 78.9%. Using PCR, for animals imported to the US these values
      were 71.8-85.3%, and for those imported to California, the simulated median that
      test positive ranged from 74.3 to 92.4%. The probability that an imported animal
      was BTV-viremic is very low regardless of the scenario selected (median
      probability=0.0%). The probability of introducing an exotic strain of BTV into
      California or the US by importing infected cattle was remote, and the current
      Office International des Epizooties (OIE) recommendation of either a final PCR
      test performed 14 days after entry into quarantine, a c-ELISA performed 28 days
      after entry into quarantine or a 100-day quarantine with no testing requirement
      was adequate to protect cattle in the US and California from an exotic strain of
      BTV.

PMID- 15579337
TI  - A cross-sectional study of epizootic lymphangitis in cart-mules in western
      Ethiopia.
AB  - A cross-sectional study was conducted to determine the prevalence of epizootic
      lymphangitis (EL) in 309 cart-mules (cart-pulling mules) in Bako and Ejaji towns,
      Western Ethiopia using clinical and microbiological examinations, between
      November 2002 and April 2003. The overall prevalence was 21% (CI=16.6-26%). The
      clinical, histological and mycological characteristics of EL in a cart-mule were
      similar with those in a horse. There was significant (chi2=133.5, P=0.001)
      association between tick infestation and EL lesions in study cart-mules. Amblyoma
      coherence and Boophilus genera were the ticks collected from lesions of cases of
      EL, and thus played a predisposing role. In conclusion, our results showed that
      EL has high prevalence in cart-mules in the two towns.

PMID- 15579338
TI  - Bayesian modeling of animal- and herd-level prevalences.
AB  - We reviewed Bayesian approaches for animal-level and herd-level prevalence
      estimation based on cross-sectional sampling designs and demonstrated fitting of
      these models using the WinBUGS software. We considered estimation of infection
      prevalence based on use of a single diagnostic test applied to a single herd with
      binomial and hypergeometric sampling. We then considered multiple herds under
      binomial sampling with the primary goal of estimating the prevalence distribution
      and the proportion of infected herds. A new model is presented that can be used
      to estimate the herd-level prevalence in a region, including the posterior
      probability that all herds are non-infected. Using this model, inferences for the
      distribution of prevalences, mean prevalence in the region, and predicted
      prevalence of herds in the region (including the predicted probability of zero
      prevalence) are also available. In the models presented, both animal- and herd
      level prevalences are modeled as mixture distributions to allow for zero
      infection prevalences. (If mixture models for the prevalences were not used,
      prevalence estimates might be artificially inflated, especially in herds and
      regions with low or zero prevalence.) Finally, we considered estimation of animal
      level prevalence based on pooled samples.

PMID- 15579339
TI  - Effects of diseases on reproductive performance in Swedish Red and White dairy
      cattle.
AB  - The objectives of this study were to evaluate the effect of diseases on days open
      (DO), days to first breeding (DFB) and days from first breeding to conception
      (DFBC) using survival analysis models, and to assess the significance of the sire
      component and its possible confounding effect. The data consisted of a random
      sample of 20% of all herds enrolled in Swedish recording system and using 100%
      artificial insemination with at least 15 Swedish Red and White cows calving in
      1991. The follow-up period was from 45 to 145 d after calving. After editing, the
      data sets had 23,927, 28,197, and 22,089 cows for days open, days to first
      breeding, and days from first breeding to conception, respectively. The Cox
      models included parity, calving season, cow milk production and age at first
      calving as fixed effects, and herd and sire as random effects. Ten disease groups
      were considered as possible risk factors for the reproductive traits. Disease
      groups were treated differently if they occurred before or after 45 d postpartum.
      Diseases occurring in the first 45 d after calving were treated as time
      independent covariates and diseases occurring after day 45 were treated as time
      dependent covariates for days open and days to first breeding. The percentages of
      censored cows were 35% for days open, 19% for days to first breeding, and 33% for
      days from first breeding to conception. Days open increased in cows with
      dystocia, stillbirth, retained placenta, metritis, or other diseases occurring in
      the first 45 d after calving, and in cows with metritis, mastitis, or other
      diseases occurring after 45 d. Days to first breeding increased in cows with
      stillbirth, retained placenta, milk fever, mastitis, foot and leg problems, or
      other diseases occurring before day 45, and in cows with metritis, mastitis, foot
      and leg problems, or other diseases occurring after 45 d. Days to first breeding
      decreased in cows treated for ovulatory dysfunctions either before or after 45 d.
      Days from first breeding to conception increased in cows with dystocia,
      stillbirth, retained placenta, metritis, or ovulatory dysfunctions occurring
      before first breeding, and in cows with mastitis occurring after first breeding.
      Although the additive genetic components were significant for all traits
      considered, the sires did not act as confounders because only a small amount of
      variability for the traits considered in this study was explained by the sires,
      with estimated heritabilities of 2% on the logarithmic scale and from 3 to 4% on
      the real scale.

PMID- 15579340
TI  - Risk factors for herdsman-reported foot-and-mouth disease in the Adamawa Province
      of Cameroon.
AB  - We analysed responses from 147 Fulani herdsmen to a questionnaire about cattle
      herd-level risk factors for foot-and-mouth disease (FMD) in the previous year.
      The study used a cross-sectional design with a stratified, two-stage random
      sample of cattle herds in the Adamawa Province of Cameroon. The questionnaire was
      pre-tested at a local cattle market before a final version was translated into
      Foulfoulde (the local Fulani dialect). Variables were screened using a
      univariable analysis and logistic multiple-regression models were developed in a
      forward-selection process. Fifty-eight percent (50-65; 90% CIs) of herdsmen
      reported FMD in their herd in the previous 12 months. Important risk factors for
      FMD in the previous 12 months included going on transhumance (OR=2.6), buying
      cattle from markets (OR=2.2), mixing of herds at watering points (OR=2.4),
      feeding cotton-seed cake (OR=3.3), buffalo near the herd (OR=2.2) and
      administrative division. For the subset of herds that went on transhumance,
      coming in contact with an FMDV-diseased herd while on transhumance was the
      strongest factor (OR=16).

PMID- 15579341
TI  - A biological network describing infection with Mycoplasma hyopneumoniae in swine
      herds.
AB  - We have made a biological model based on a Bayesian network for risk factors for
      infection with Mycoplasma hyopneumoniae (Mycoplasma) in slaughter pigs;
      prevalence of infection is based on veterinary examinations. The model is a
      probabilistic/stochastic determination based on the inherent biological
      uncertainty of the severity of infection with Mycoplasma and the derived
      stochastic effects on productivity for the herd. The conditional probabilities in
      the Bayesian network are based on published studies and expert opinions. We used
      the model to calculate how the risk factors and our evidence about the herd
      influenced our view on the severity of Mycoplasma, and how our view changed when
      we had more veterinary evidence. We also show how one can use the model to deal
      with conflicting examinations.

PMID- 15579342
TI  - The effect of antimicrobial growth promoter withdrawal on the health of weaned
      pigs in Finland.
AB  - The use of the antimicrobial growth promoters (AGPs) carbadox and olaquindox has
      been banned in the European Union (EU) since September 1999. We studied the
      effects of the withdrawal on the health of weaned piglets on two types of piglet
      producing farms (farrowing herds and farrow-to-finish herds) from the different
      regions of Finland. Farms with no major problems with post-weaning diarrhoea were
      selected for the study to better evaluate the effect of AGPs alone. Data on
      production, medication and incidence of diarrhoea were collected from 73 farms
      during 1 year after the withdrawal. On 29 of these farms, the data collection
      began 4 months before the withdrawal. The health management of the pigs is
      considered good in Finland, and special attention has been paid to improve the
      husbandry practices and management of the farms. Eighty-two percent of the farms
      in the study were free of both Mycoplasma hyopneumoniae and Sarcoptes scabiei
      infection. Brachyspira hyodysenteriae infection was not detected in any of the
      farms. The median number of sows in the herds was 56.0 (IQR=43.0; 72.5) in 2000.
      The level of antimicrobial use in each herd was classified as low, moderate and
      high when the percentage of weaned pigs treated for diarrhoea during a 4-month
      period was 0-5%, 6-19% and > or =20%, respectively. Only on four herds (14%),
      there was an increase in the level of antibiotic use after the AGP withdrawal,
      when seasonally corresponding 4-month periods were compared. Fourty-one percent
      of these 29 farms were categorized as low users of antimicrobials, 38% as
      moderate users and 21% as high users. The level of antimicrobial use for
      treatment of diarrhoea after weaning (and the incidence of diarrhoea in weaned
      piglets) did not increase significantly after the withdrawal of AGPs from weaner
      feeds according to farmers' evaluations. In this study, the Escherichia coli
      infection was the most-common cause of diarrhoea in weaned pigs. The age at
      weaning did not change after the withdrawal of AGPs.

PMID- 15579343
TI  - Associations between management, climate, and Escherichia coli O157 in the faeces
      of feedlot cattle in the Midwestern USA.
AB  - Our objective was to generate hypotheses for potential on-farm control strategies
      for Escherichia coli O157 by identifying associations between management
      practices and climate, and the presence of E. coli O157 in feedlot cattle. Faeces
      were obtained from 10,622 cattle in 711 pens on 73 feedlots between May and
      August 2001. Management and climate information was obtained by questionnaire and
      observation at the time of sampling. The prevalence of E. coli O157 was 10.2% at
      the sample level, 52.0% at the pen-level, and 95.9% at the feedlot-level. The
      factors associated with the presence of E. coli O157 in cattle faeces were the
      frequency of observing cats in the pens or alleys (most common when observed
      daily), the presence of E. coli O157 in the water tanks (positive association),
      the historical use of injectable mass medication (positive association), the use
      of antibiotics in the ration or water (negative association), the wetness of the
      pen, number of cattle in the pen (negative association), wind velocity (positive
      association), and height of the feed bunk (positive association).

PMID- 15579344
TI  - Factors associated with the presence of Escherichia coli O157 in feedlot-cattle
      water and feed in the Midwestern USA.
AB  - Our objective was to generate hypotheses about associations between management,
      climate, and the presence of Escherichia coli O157 in feedlot-cattle water tanks
      and in feedlot-cattle feed. Water samples from 710 tanks on 73 feedlots, and feed
      samples from a subset of 504 pens on 54 feedlots, in four US states were tested
      for E. coli O157. Management and climate factors were ascertained by survey and
      observation. Escherichia coli O157 were isolated from 13% of the water tanks and
      at least one water tank was positive on 60% of the feedlots. The factors
      significantly associated with E. coli O157 in water were greater percentage of
      cattle shedding E. coli O157 in faeces within the same pen, higher concentration
      of total E. coli in the water, lack of the clarity of the water, the use of fly
      traps, the reported frequency of rodent sightings in the pen or alley area, and
      the weather at the time of sampling. Escherichia coli O157 were isolated from
      14.9% of the feed samples obtained from the feedbunks. Factors positively
      associated with E. coli O157 in feed were higher heat index at the time of
      sampling, the presence of cottonseed meal in the ration, and the feedlot location
      (state). Coliform counts in feed, presence of E. coli O157 in water tanks and
      faecal prevalence of E. coli O157 were not associated with the presence of E.
      coli O157 in feed.

PMID- 15579345
TI  - Ability of veterinary pathologists to diagnose classical swine fever from
      clinical signs and gross pathological findings.
AB  - Clinical signs recorded in a classical swine fever (CSF)-suspect situation and
      the results of the subsequent post-mortem examination (PME) from swine submitted
      to post-mortem during the 1997-1998 CSF epidemic in the Netherlands, were
      presented in an experiment as anonymous cases (without knowledge of the actual
      infection status of the submission) to five veterinary pathologists for their
      judgment: CSF-suspect or non-suspect. It was presented to them in two
      hypothetical situations: country was free of CSF for 5 years and CSF was detected
      in the country 2 weeks ago. Subsequently, their judgment was compared to the gold
      standard (infection status of the submission on the basis of an immunofluoresence
      assay on tissue samples) and the sensitivity (Se) and specificity (Sp) of
      clinical diagnosis was estimated. Furthermore, intra- and inter-pathologist
      agreement on pathological diagnosis was measured. Adding information on clinical
      signs to information on PME resulted in a significant increase in median Se and a
      significant decrease in median Sp for a clinical judgment by pathologists. Also,
      median Se was significantly higher-and Sp significantly lower-for a clinical
      judgment by pathologists in a situation in which CSF was detected 2 weeks ago in
      the country compared to the situation in which the country had been free of CSF
      for 5 years. Apparently, the internal threshold of pathologists is severely
      adjusted depending on the actual disease situation in a country. Intra-rater
      agreement ranged from fair to almost perfect for a clinical diagnosis on the
      basis of PME. There was considerable variation between pathologists, especially
      if clinical diagnosis was based on the combined information on PME and clinical
      signs observed in the herd. Inter-rater agreement was substantial for the
      diagnosis based on information on PME. Inter-rater agreement was considerably
      lower for the diagnosis based on the combined information on PME and clinical
      signs observed in the herd.

PMID- 15579346
TI  - Health and welfare of dairy cows in different husbandry systems in Switzerland.
AB  - Our objective was to compare health and welfare of dairy cows kept in three types
      of husbandry systems: (1) tie stalls with regular exercise in summer but minimal
      outdoor access during winter (the reference level for analyses); (2) tie stalls
      with regular exercise in an exercise yard or pasture throughout the year; (3)
      loose-housing with regular access to an outdoor exercise yard or pasture. A total
      of 134 farms were visited (two to) three times in two years. Cows were examined
      for lameness, skin alterations at the hock joints, scars or injuries at the
      teats, and skin injuries at other locations. Lying and standing-up behavior were
      also evaluated. Farmers were requested to record the incidence of medical
      treatments for the whole observation period. A multivariable logistic-regression
      analysis was performed for each indicator of health and welfare with husbandry
      type, aspects of the housing system, farm characteristics, and management
      routines as the predictor variables. For welfare indicators recorded on
      individual animals, regression was performed correcting for clustering of
      observations within herds by Generalized Estimation Equation. Risk factors for
      the incidence of medical treatments were analyzed in a negative-binomial
      regression model. The odds for lameness were reduced for tie stalls with regular
      exercise throughout the year (OR=0.7). The prevalence of alterations at the hock
      joints was lower in loose-housing with regular outdoor exercise (OR=0.4). Teat
      injuries were less frequent in loose-housing with regular outdoor exercise
      (OR=0.1) and tie stalls with regular exercise (OR=0.4). Farms with loose-housing
      and regular outdoor exercise had a lower incidence of medical treatments (IR=0.6)
      than reference level farms.

PMID- 15579347
TI  - Quantification of the spread of Mycoplasma hyopneumoniae in nursery pigs using
      transmission experiments.
AB  - Mycoplasma hyopneumoniae (M. hyopneumoniae) is present in almost all swine herds
      worldwide, but transmission of the pathogen through herds is not yet fully
      clarified. The aim of this study, performed in 2003, was to investigate and to
      quantify the transmission of M. hyopneumoniae under experimental conditions by
      means of an adjusted reproduction ratio (Rn). This Rn-value, calculated according
      to the final size method, expresses the mean number of secondary infections due
      to one typical infectious piglet during the nursery period. The period lasted
      from 4 to 10 weeks of age, corresponding with the nursery period used in most
      European production systems. Additionally, a comparison was made between
      transmissions of highly virulent and low virulent isolates. Forty-eight weaned
      piglets, free of M. hyopneumoniae, were housed in six separate pens. During 6
      weeks, two animals experimentally infected with M. hyopneumoniae were housed
      together with six susceptible piglets. At the end of the study, the number of
      contact-infected animals was determined by the use of nPCR on bronchoalveolar
      lavage fluid. The Rn-values of the highly virulent and the low virulent isolates
      were estimated to be 1.47 (0.68-5.38) and 0.85 (0.33-3.39), respectively. No
      significant difference between the groups was found (P=0.53). The overall Rn was
      estimated to be 1.16 (0.94-4.08). Under the present experimental conditions, the
      transmission of M. hyopneumoniae, assessed for the first time by a reproduction
      ratio, shows that one piglet infected before weaning will infect on average one
      penmate during the nursery phase.

PMID- 15579349
TI  - Defining and measuring patient safety.
AB  - Despite the growing demand for improved safety in health care, debate remains
      regarding the magnitude of the problem and the degree to which harm is
      preventable. To a great extent, this debate stems from variation in the
      definition and methods for measuring safety, its "shadow" error, and the degree
      of preventability. This article reviews the definition of safety and error,
      discusses approaches to measuring safety, and provides a framework for
      investigating incidents that unveils how the systems under which care is
      delivered may contribute to adverse incidents.

PMID- 15579350
TI  - Failure mode and effects analysis application to critical care medicine.
AB  - In July 2001, the United States Joint Commission on Accreditation of Health care
      Organizations adopted a new leadership standard that requires department heads in
      health care organizations to perform at least one Failure Mode and Effects
      Analysis (FMEA) every year. This proactive approach to error prevention has
      proven to be highly effective in other industries, notably aerospace, but remains
      untested in acute care hospitals. For several reasons, the intensive care unit
      (ICU) potentially is an attractive setting for early adoption of FMEA; however,
      successful implementation of FMEA in ICUs is likely to require strong, effective
      leadership and a sustained commitment to prevent errors that may have occurred
      rarely or never before in the local setting. This article describes FMEA in
      relation to critical care medicine and reviews some of the attractive features
      together with several potential pitfalls that are associated with this approach
      to error prevention in ICUs.

PMID- 15579351
TI  - An irreplaceable safety culture.
AB  - Intensive care unit (ICU) clinicians are sources of errors and of resilience.
      When they learn how to juggle many competing goals, remain vigilant, and tell
      safety stories--all in the context of changing technologies and demand--they can
      create safe settings of care. Other strategies (eg, using computerized tools and
      implementing safety procedures) are important, but alone they are not sufficient.
      An ICU needs a safety culture that is rooted in a committed leadership, the
      acknowledgment that error is inevitable, a reporting system, and continuous
      learning. The all too common norm, "no harm no foul," is an obstacle. ICU leaders
      can use a campaign strategy to spread the safety practices that sustain a safety
      culture. They should attend to the political, marketing, and military aspects of
      such campaigns and recognize that people's time and attention are limited and
      built projects from existing ongoing pilots. Pilots can compete for people's
      attention; it has pull when it exemplifies a moral idea, simplifies work, and
      gives the health care professional more control and feedback. Under these
      conditions, the campaign will release individuals' passions and add energy and
      insight to the campaign itself.

PMID- 15579352
TI  - Critical care organization.
AB  - The organizational structure of critical care services likely affects the quality
      of patient care, and ultimately, patient outcomes. Based on the available data,
      the ideal intensive care unit would be a closed-unit staffed by dedicated
      intensivists. Whether or not around-the-clock intensivist staffing is necessary,
      however, is debatable. Because financial realities preclude all units from being
      ideal, alternative strategies for organization must be explored.

PMID- 15579353
TI  - The electronic medical record, safety, and critical care.
AB  - The goal of this article is to introduce the elements of the Electronic Medical
      Record as they pertain to critical care medicine including order communications
      and decision support.

PMID- 15579354
TI  - Management of the critically ill patient in the emergency department: focus on
      safety issues.
AB  - The management of the critically ill patient in the emergency department (ED) is
      an evolving process. Currently there is sufficient evidence substantiating the
      central role of the ED in the management of critically ill patients.
      Understanding the tremendous impact ED physicians have in the care of critically
      ill patients will serve as an impetus for emergency medicine residents to pursue
      critical care specialty. With the continuous increment of critically ill patients
      presenting to EDs throughout the country, the nationwide shortage of critical
      care physicians, and the limited availability of intensive care unit eds
      throughout hospital systems, there will be an increased focus on managing these
      patients in the ED. As the field of emergency medicine continues to mature, the
      ED physician must take notice of the potential risk areas within the management
      of the critically ill patient to continue to improve these patients' short- and
      long-term survival.

PMID- 15579355
TI  - Medication safety and transfusion errors in the ICU and beyond.
AB  - The modern day intensive care unit (ICU) is a place in which patients can receive
      continuous monitoring of physiologic variables with concentrated patient
      observation and care. Despite the "intensive care," errors do occur. This article
      reviews medication and transfusion errors, including the different types, causes,
      and possible solutions to prevent these errors from occurring in ICUs and the
      hospital at large.

PMID- 15579356
TI  - Managing infection in the critical care unit: how can infection control make the
      ICU safe?
AB  - The goal of this article is to use ventilator-associated pneumonia (VAP) as a
      prototype for nosocomial infections to explore the issues of patient safety and
      infection control. To do this, we review disease-specific aspects of VAP, develop
      a brief working definition of patient safety, and then determine how the concepts
      of infection control fit into the broader context of patient safety.

PMID- 15579357
TI  - Safety in training and learning in the intensive care unit.
AB  - Resident and subspecialty fellow trainees in the intensive care unit (ICU)
      present risks for patient safety because of their inexperience yet offer
      opportunities to promote safe patient care because of their around-the-clock
      presence and their involvement in frontline processes of care. Most trainees
      approach their ICU experiences without previous education in performance
      improvement or patient safety. This article reviews the barriers that are faced
      by residents in providing safe patient care and outlines the nature of a patient
      safety curriculum that could tap the opportunities that are presented by trainees
      to promote safer patient care.

PMID- 15579358
TI  - Can regulation improve safety in critical care?
AB  - This article examines national and state safety practice initiatives, including
      the Centers for Medicare and Medicaid Services quality focus, federal and state
      outcomes reporting, and consumer access to outcomes data. The efforts of national
      and regional legislators and health care institutions to create regulations for
      staffing and technology to reduce medical errors is reviewed. The potential of a
      unified cooperative effort from all stakeholders to implement the above
      initiatives to improve intensive care unit safety practices is discussed.

PMID- 15579359
TI  - The future of critical care.
AB  - Critical care has become an important part of the health care system; however, it
      still is provided in a heterogeneous, and likely suboptimal, fashion. Future
      challenges will include providing an adequate workforce; ensuring critical care
      is delivered to the right patients at the right time; converting advances in our
      understanding of the biology of critical illness into improved care and outcomes;
      and partnering successfully with patients, families, and society in forging the
      critical care of the future.

PMID- 15579361
TI  - Allergens.
AB  - Exposure to allergens is a trigger for symptoms in sensitized individuals with
      asthma. This is especially true for allergens primarily found indoors but can be
      true for outdoor allergens with sufficiently high exposure. The role of allergens
      in attacks can be subtle in that they provide the underlying inflammation
      necessary for other nonspecific agents to have an effect.

PMID- 15579362
TI  - The effects of outdoor air pollution and tobacco smoke on asthma.
AB  - Outdoor air pollution and environmental tobacco smoke adversely affect health in
      persons with asthma. Increased levels of ozone, particulate matter, and
      environmental tobacco smoke have been associated with increased asthma symptoms
      and health care use and with reduced lung function. These air contaminants have
      proinflammatory actions that can magnify existing lower airway inflammation in
      patients with asthma. Exposure to air contaminants can increase the risk of
      developing asthma in susceptible persons. Outdoor air pollution and environmental
      tobacco smoke may affect allergen-induced inflammation by initiating TH(2)
      responses to antigens or by exacerbating such inflammation in persons already
      sensitized.

PMID- 15579363
TI  - Asthma associated with exercise.
AB  - Exercise is a potent stimulus to asthma. The diagnosis is not always
      straightforward, and health care providers should have a high index of suspicion.
      Treatment usually controls exercise-induced asthma but usually requires therapy
      tailored for each individual patient.

PMID- 15579364
TI  - Infectious triggers of asthma.
AB  - There is abundant evidence that asthma is frequently exacerbated by infectious
      agents. Several viruses have been implicated in the inception and exacerbation of
      asthma. Recent attention has been directed at the role of infections with the
      atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae as agents
      capable of triggering asthma exacerbations and potentially as inciting agents for
      asthma. This article examines the evidence for interaction between specific
      infectious agents and exacerbations of asthma, including the immunopathology of
      infection-triggered asthma, and the current therapeutic options for management.

PMID- 15579365
TI  - Rhinosinusitis and pediatric asthma.
AB  - Rhinosinusitis is a common disease in patients of all age groups. Rhinosinusitis
      arises from a variety of infectious and inflammatory mechanisms. There is ample
      evidence that rhinosinusitis can directly influence asthma. There is also growing
      evidence that rhinosinusitis may be associated with asthma as different
      manifestations of the same disorder. A great deal of future research is required
      to fully elucidate the different mechanisms whereby rhinosinusitis influences or
      associates with asthma, but it is clear that rhinosinusitis needs to be
      considered in patients with severe or refractory asthma.

PMID- 15579366
TI  - The relationship of psychologic stress with childhood asthma.
AB  - The psychologic influence on childhood asthma has long been a subject of
      investigation and controversy. This article illustrates the evidence that
      psychologic stress is related to children with asthma. Individual experience, the
      impact of family and neighborhood, the effect of caregiver mental status, and the
      presence of negative psychologic events affect symptoms and management. The
      pathways through which these factors influence asthma are mediated through
      cognitive and biologic mechanisms, with evidence indicating changes in behavior
      and alteration in immune response as underlying mechanisms. Psychologic issues
      are important in the patient with severe asthma. The mind-body paradigm that
      links psychologic stress to disease is necessary when considering the global
      evaluation of childhood asthma.

PMID- 15579367
TI  - Patient-identified barriers to asthma treatment adherence: responses to
      interviews, focus groups, and questionnaires.
AB  - This article reviews 32 patient-interview studies that revealed that the most
      common barriers to adherence revealed by patients included concerns about drug
      safety and cost and a belief that the patient's asthma was not severe enough to
      require daily treatment. Important but less commonly cited concerns included
      worry about dependence or diminished effectiveness with long-term use of the
      medication. Children and their parents expressed concerns about safety,
      dependence, peer stigmatization, and parent-child conflict over taking
      medication. Low-income and minority patients cited similar concerns and barriers
      that included cost, difficulty of obtaining medication, daily life hassles, and a
      general distrust of the medical establishment. The information obtained from
      patients' perspectives indicates the need to reappraise current strategies for
      the management of asthma, including a more flexible approach to the use of expert
      guidelines for the treatment of asthma.

PMID- 15579368
TI  - Gastroesophageal reflux: a potential asthma trigger.
AB  - Gastroesophageal reflux (GER) is a potential trigger of asthma. Approximately 77%
      of asthmatics report heartburn. GER is a risk factor for asthma-related
      hospitalization and oral steroid burst use. Asthmatics may be predisposed to GER
      development because of a high prevalence of hiatal hernia and autonomic
      dysregulation and an increased pressure gradient between the abdominal cavity and
      the thorax, over-riding the lower esophageal sphincter pressure barrier. Asthma
      medications may potentiate GER. Potential mechanisms of esophageal acid-induced
      bronchoconstriction include a vagally mediated reflex, local axonal reflexes,
      heightened bronchial reactivity, and microaspiration, all resulting in neurogenic
      inflammation. Anti-reflux therapy improves asthma symptoms in approximately 70%
      of asthmatics with GER. A 3-month empiric trial of twice-daily proton pump
      inhibitor given 30 to 60 minutes before breakfast and dinner can identify
      asthmatics who have GER as a trigger of their asthma.

PMID- 15579369
TI  - Food allergy and additives: triggers in asthma.
AB  - Exposure to food allergens can cause a varied pattern of respiratory symptoms,
      with allergic responses ranging from asthma symptoms to occupational asthma. Food
      allergy in a patient presenting as asthma tends to indicate a more severe disease
      constellation. Patients with underlying asthma experience more severe and life
      threatening allergic food reactions. When a food reaction involves respiratory
      symptoms, it is almost always a more severe reaction compared with reactions that
      do not involve the respiratory tract. Susceptible patients may even react to a
      causative food on inhalation without ingestion. However, isolated asthma or
      rhinitis symptoms without concomitant cutaneous or gastrointestinal symptoms are
      rare events.

PMID- 15579370
TI  - Medications as asthma triggers.
AB  - Certain medications can generate asthma symptoms, with the potential to cause
      considerable morbidity. This article focuses on the common drugs that have the
      potential to cause distinct respiratory reactions in asthmatics: aspirin and
      other nonsteroidal anti-inflammatory drugs, beta-blockers, and angiotensin
      converting enzyme inhibitors. The means by which these medications can trigger
      asthma vary in terms of acuity of onset, severity, and the mechanisms involved.
      The general and most practical approach is avoidance and cautious use of these
      drugs in asthmatics. However, these classes of medications can exert a major role
      in the management of common and serious diseases. Fortunately, controller therapy
      for asthma and alternative or more selective medications for the treatment of
      these conditions are now available.

PMID- 15579371
TI  - Occupational exposures as triggers of asthma.
AB  - The prevalence of occupational asthma is rising, possibly due to the introduction
      of different chemicals and substances in the workplace. Etiologic agents include
      organic and inorganic compounds that are encountered in a variety of industries.
      Early diagnosis, adequate management of inflammation, and prevention of further
      exposure are essential to occupational asthma management. Reducing complications
      and disability while providing work rehabilitation should be the ultimate goal of
      the health care provider. This article discusses these issues and gives guidance
      to the clinician treating patients with possible occupational asthma.

PMID- 15579372
TI  - Adherence modifies the regulation of gene expression induced by interleukin-10.
AB  - Interleukin-10 (IL-10) is a well known anti-inflammatory cytokine. However, we
      previously showed that it could present pro-inflammatory properties on human
      monocytes in the absence of adherence. In the present study, using macroarray
      technology, we analyzed the effects of IL-10 and adherence on the expression of
      1050 genes in human monocytes cultured for 3 hours on plastic or Teflon(R) (to
      avoid adherence). Adherence alone induced specifically the expression of 12 genes
      and repressed that of 25 genes. In adherent monocytes, IL-10 induced the
      expression of 21 genes and repressed that of 50 genes. In non-adherent monocytes,
      IL-10 induced the expression of 45 genes and repressed that of 67. Only 3 common
      genes were induced while 35 common genes were repressed by IL-10 in the two
      culture conditions. Interestingly, we showed that IL-10 modulated conversely on
      Teflon(R) and plastic the expression of 16 genes, of which SOCS molecules,
      coproporphyrinogen oxidase, matrix metalloproteinases and complement receptor-1
      (CD35). This study demonstrates that adherence has profound modulatory effects on
      the properties and the signaling induced by IL-10. The discovery that IL-10 can
      inhibit the production of coproporphyrinogen oxidase (an enzyme involved in the
      synthesis of heme) may shed some lights on the mechanisms of anaemia induced by
      IL-10. Furthermore, the inhibition of the expression of SOCS1 by IL-10 in the
      absence of adherence, may explain its priming effects on a subsequent LPS
      stimulation that we previously described.

PMID- 15579373
TI  - Normal platelets possess the soluble form of IL-6 receptor.
AB  - Interleukin 6 is a multifunctional cytokine that exerts its biological activity
      through binding to an 80 Kd specific receptor (IL-6Ralpha) and a 130 Kd signal
      transducing unit (gp130). A 55 Kd soluble IL-6R (IL-6sR) has also been described
      which, after binding to IL-6 is also able to activate gp130. The presence of IL
      6Ralpha was described in some megakaryoblastic cell lines but is still
      controversial in normal megakaryocytes. In this study we demonstrate the presence
      of intraplatelet IL-6sR by Western blot through the appearance of a 55 Kd protein
      and the finding of detectable amounts of IL-6sR in the platelet content by ELISA
      technique. Besides, we showed IL-6sR release during platelet activation induced
      by thrombin and a complex of ADP and epinephrine. IL-6Ralpha on platelet membrane
      could not be found neither by Western blot nor by flow cytometry. The IL-6sR
      released during platelet activation and complexed to IL-6 could act on cell types
      such as endothelial cells that do not possess IL-6Ralpha through binding to
      gp130.Besides, since we could not find IL-6R on platelet membrane, the
      potentiating effect of IL-6 on platelet function could be explained through
      binding of IL-6sR/IL-6 complex to platelet membrane gp130.

PMID- 15579374
TI  - Interleukin-8 in whole blood and clinical status in cystic fibrosis.
AB  - Cytokines and polymorphonuclear leukocytes play a key role in immune mediated
      inflammation in progressive pulmonary damage due to cystic fibrosis. The aim of
      this study is to establish a simple measure of the host's propensity to secrete
      inflammatory cytokines and to correlate this with clinical status. Patients
      (n=44, median age 16 years) with the DeltaF 508 mutation (homozygous) were
      grouped according to their Shwachman score: Patients with mild disease (Shwachman
      score 71-100 points, group A, n=22, median FEV(1) 79%) were compared with those
      with more severe disease (Shwachman score 41-55 points, group B, n=22, median
      FEV(1) 55%) and age-matched controls (group C, n=22, median FEV(1) 102%). Whole
      blood was stimulated with 5 ng of lipopolysaccharide (LPS). Interleukin-8 (IL-8)
      was measured by chemiluminescent immunometric assay (DPC, Bad Nauheim, Germany).
      Though there was a significant difference at baseline for IL-8 (median group
      A/B/C 6.1/30.5/5.8 pg/ml; p<0.001), there was no significant difference after
      stimulation. Moreover, in Pseudomonas aeruginosa positive (Psa+) patients (n=26)
      there was a significant negative correlation (r=-0.539; p<0.004) between baseline
      IL-8 and FEV(1) (%). Clinical course and lung function (in Psa+) correlate with
      IL-8 levels.

PMID- 15579375
TI  - Cytokines and adhesion molecules in multiple sclerosis patients treated with
      interferon-beta1b.
AB  - Multiple sclerosis (MS), an inflammatory, demyelinating disease of the central
      nervous system (CNS), is thought to be caused by a T cell-mediated attack on CNS
      myelin and axons. Recombinant interferon (IFN)-beta is an established treatment
      of multiple sclerosis, and is known to reduce the number of disease relapses and
      the development of irreversible symptoms and signs of disease. The mechanism of
      action of IFN-beta treatment is, however, not completely understood. Previous
      studies have suggested major effects on mononuclear cell cytokine production and
      T cell migration, but results have been inconsistent. We found decreases in CD4
      and CD8 T cell expression of the CD49d/VLA-4 molecule, increases in plasma
      concentrations of soluble vascular cell adhesion molecule (sVCAM-1), and
      increases in plasma concentrations of tumor necrosis factor and interleukin (IL)
      12 p40 chain in patients with MS who were initiated on de novo treatment with IFN
      beta1b. We found only minor associations between the different changes induced by
      IFN-beta1b-treatment. Our findings are consistent with changes in T cell
      expression of CD49d/VLA-4 and induction of sVCAM-1 as important effects of
      treatment with IFN-beta1b in multiple sclerosis, whereas the role of changes in
      TNF and IL-12 p40 chain concentrations is more difficult to interpret.

PMID- 15579376
TI  - Effect of leukemia inhibitory factor in experimental cisplatin neuropathy in
      mice.
AB  - In this study, the effect of leukemia inhibitory factor (LIF) on cisplatin (CDDP)
      induced neuropathy was evaluated. Mice were treated with CDDP, 2 mg/kg i.p. twice
      a week nine times. During the last week some of the mice were also injected with
      LIF, 2 mug/kg s.c. every other day for a total of four injections. Development of
      neuropathy was evaluated with changes in tail flick latency and sensory nerve
      conduction velocity (NCV). At the end of the treatment period dorsal root ganglia
      (DRG) were microscopically examined. Some of the DRGs were explanted into
      extracellular matrix, covered with culture medium and incubated for 3 days.
      During and at the end of the incubation, cellular migration and axonal outgrowth
      from the DRGs were quantified. LIF proved effective in reversing the increase in
      tail flick latency (p<0.05) and improving the reduction in NCV induced by CDDP.
      CDDP led to smaller nuclear and somatic size in neurons, while with LIF, the
      latter was restored to control values (p<0.01). No apoptotic nucleus was observed
      among DRG neurons while very few and moderate numbers detected among satellite
      and Schwann cells, respectively. With LIF, none of the cells had apoptosis. CDDP
      caused a decrease in the number of migrating cells and in the length of
      outgrowing axons while LIF treatment restored both capacities (p<0.05) In
      conclusion, in CDDP-induced neuropathy, LIF was found to be effective in
      correcting some functional and morphological deteriorations related with major
      involvement of Schwann cells.

PMID- 15579377
TI  - CXCL8 modulates human intestinal epithelial cells through a CXCR1 dependent
      pathway.
AB  - BACKGROUND: CXCL8 (previously known as Interleukin-8), a member of the alpha
      chemokine family of chemotactic cytokines, stimulates intestinal neutrophil
      activation and chemotaxis. As intestinal epithelial cells have been recently
      shown to produce CXCL8, the aim of this study was to identify functional
      activities of CXCL8 on intestinal epithelial cells. METHODS: The expression of
      CXCL8 receptors CXCR1 and CXCR2 was assessed by RT-PCR and FACS analysis in human
      Caco-2 and HT-29 cells. The effects of CXCL8 on intestinal epithelial
      proliferation were assessed with colorimetric MTT assays and the effects on
      epithelial restitution with an in vitro migration model using Caco-2 and HT-29
      cells. RESULTS: While the expression of both CXCR1 mRNA and protein could be
      demonstrated by RT-PCR and FACS analysis in human Caco-2 and HT-29 cells, no
      expression of CXCR2 was observed in these cell lines. Colorimetric MTT assays
      revealed that CXCL8 does not modulate cell proliferation in HT-29 and Caco-2
      cells. In contrast, CXCL8 significantly enhanced intestinal epithelial migration
      in an in vitro migration model of HT-29 and Caco-2 cells. Enhancement of
      intestinal epithelial cell migration by CXCL8 was partially CXCR1-dependent and
      TGFbeta-independent. CONCLUSION: CXCL8 exerts functional effects on intestinal
      epithelial cells that may be relevant for intestinal inflammation and mucosal
      healing.

PMID- 15579378
TI  - Snakes across the Strait: trans-Torresian phylogeographic relationships in three
      genera of Australasian snakes (Serpentes: Elapidae: Acanthophis, Oxyuranus, and
      Pseudechis).
AB  - We analyze the phylogeny of three genera of Australasian elapid snakes
      (Acanthophis-death adders; Oxyuranus-taipans; Pseudechis-blacksnakes), using
      parsimony, maximum likelihood, and Bayesian analysis of sequences of the
      mitochondrial cytochrome b and ND4 genes. In Acanthophis and Pseudechis, we find
      evidence of multiple trans-Torresian sister-group relationships. Analyses of the
      timing of cladogenic events suggest crossings of the Torres Strait on several
      occasions between the late Miocene and the Pleistocene. These results support a
      hypothesis of repeated land connections between Australia and New Guinea in the
      late Cenozoic. Additionally, our results reveal undocumented genetic diversity in
      Acanthophis and Pseudechis, supporting the existence of more species than
      previously believed, and provide a phylogenetic framework for a reinterpretation
      of the systematics of these genera. In contrast, our Oxyuranus scutellatus
      samples from Queensland and two localities in New Guinea share a single
      haplotype, suggesting very recent (late Pleistocene) genetic exchange between New
      Guinean and Australian populations.

PMID- 15579379
TI  - Bayesian phylogenetic analysis reveals two-domain topology of S
      adenosylhomocysteine hydrolase protein sequences.
AB  - S-Adenosylhomocysteine hydrolase (SahH) is involved in the degradation of the
      compound which inhibits methylation reactions. Using a Bayesian approach and
      other methods, we reconstructed a phylogenetic tree of amino acid sequences of
      this protein originating from all three major domains of living organisms. The
      SahH sequences formed two major branches: one composed mainly of Archaea and the
      other of eukaryotes and majority of bacteria, clearly contradicting the three
      domain topology shown by small subunit rRNA gene. This topology suggests the
      occurrence of lateral transfer of this gene between the domains. Poor resolution
      of eukaryotes and bacteria excluded an ultimate conclusion in which out of the
      two domains this gene appeared first, however, the congruence of the secondary
      branches with SS rRNA and/or concatenated ribosomal protein datasets phylogenies
      suggested an "early" acquisition by some bacterial and eukaryotic phyla.
      Similarly, the branching pattern of Archaea reflected the phylogenies shown by SS
      rRNA and ribosomal proteins. SahH is widespread in Eucarya, albeit, due to
      reductive evolution, it is missing in the intracellular parasite Encephalitozoon
      cuniculi. On the other hand, the lack of affinity to the sequences from the alpha
      Proteobacteria and cyanobacteria excludes a possibility of its acquisition in the
      course of mitochondrial or chloroplast endosymbioses. Unlike Archaea, most
      bacteria carry MTA/SAH nucleosidase, an enzyme involved also in metabolism of
      methylthioadenosine. However, the double function of MTA/SAH nucleosidase may be
      a barrier to ensure the efficient degradation of S-adenosylhomocysteine,
      specially when the intensity of methylation processes is high. This would explain
      the presence of S-adenosylhomocysteine hydrolase in the bacteria that have more
      complex metabolism. On the other hand, majority of obligate pathogenic bacteria
      due to simpler metabolism rely entirely on MTA/SAH nucleosidase. This could
      explain the observed phenetic pattern in which bacteria with larger (>6 Mb
      million base pairs) genomes carry SAH hydrolase, whereas bacteria that have
      undergone reductive evolution usually carry MTA/SAH nucleosidase. This suggests
      that the presence or acquisition of S-adenosylhomocysteine hydrolase in bacteria
      may predispose towards higher metabolic, and in consequence, higher genomic
      complexity. The good examples are the phototrophic bacteria all of which carry
      this gene, however, the SahH phylogeny shows lack of congruence with SSU rRNA and
      photosyntethic genes, implying that the acquisition was independent and
      presumably preceded the acquisition of photosyntethic genes. The majority of
      cyanobacteria acquired this gene from Archaea, however, in some species the sahH
      gene was replaced by a copy from the beta- or gamma-Proteobacteria.

PMID- 15579380
TI  - Population genetics and phylogenetic inference in bacterial molecular
      systematics: the roles of migration and recombination in Bradyrhizobium species
      cohesion and delineation.
AB  - A combination of population genetics and phylogenetic inference methods was used
      to delineate Bradyrhizobium species and to uncover the evolutionary forces acting
      at the population-species interface of this bacterial genus. Maximum-likelihood
      gene trees for atpD, glnII, recA, and nifH loci were estimated for diverse
      strains from all but one of the named Bradyrhizobium species, and three unnamed
      "genospecies," including photosynthetic isolates. Topological congruence and
      split decomposition analyses of the three housekeeping loci are consistent with a
      model of frequent homologous recombination within but not across lineages,
      whereas strong evidence was found for the consistent lateral gene transfer across
      lineages of the symbiotic (auxiliary) nifH locus, which grouped strains according
      to their hosts and not by their species assignation. A well resolved Bayesian
      species phylogeny was estimated from partially congruent glnII+recA sequences,
      which is highly consistent with the actual taxonomic scheme of the genus.
      Population-level analyses of isolates from endemic Canarian genistoid legumes
      based on REP-PCR genomic fingerprints, allozyme and DNA polymorphism analyses
      revealed a non-clonal and slightly epidemic population structure for B.
      canariense isolates of Canarian and Moroccan origin, uncovered recombination and
      migration as significant evolutionary forces providing the species with internal
      cohesiveness, and demonstrated its significant genetic differentiation from B.
      japonicum, its sister species, despite their sympatry and partially overlapped
      ecological niches. This finding provides strong evidence for the existence of
      well delineated species in the bacterial world. The results and approaches used
      herein are discussed in the context of bacterial species concepts and the
      evolutionary ecology of (brady)rhizobia.

PMID- 15579381
TI  - The shaping of mitochondrial DNA phylogeographic patterns of the brown hare
      (Lepus europaeus) under the combined influence of Late Pleistocene climatic
      fluctuations and anthropogenic translocations.
AB  - The phylogeographic structure of the brown hare (Lepus europaeus) was studied by
      analysing mtDNA control region sequences of 98 individuals from continental and
      insular Greece, Bulgaria, Cyprus and northern Israel, together with 44 published
      sequences from Italy and central Europe. We found two distinct clades separated
      by an average nucleotide divergence of 6.6%, which may correspond to a Balkan and
      to an Asia Minor refugium. The estimated time of separation of the two clades was
      dated back to 105,000- 490,000 years ago. These two clades coexist in the area of
      northeastern Greece and Bulgaria, most likely as a result of a post-glacial
      northward expansion. Within the southern Balkan refugium, network analyses showed
      geographical structuring, which supports the hypothesis of several isolated Late
      Pleistocene populations. The central European and Italian populations appear to
      have originated from a non-detected northern Balkan population that was
      genetically closely related to some northern Greek populations, as a result of
      postglacial expansion, translocations or a combination of both. Moreover, several
      cases of ancient and recent translocations by humans were detected, especially
      for some island populations, while the eastern Aegean islands off the Asia Minor
      coast were most likely colonized naturally through Late Pleistocene land bridge
      connection. The genetic analysis presented here provides a framework for
      designing proper conservation and management guidelines for this species.

PMID- 15579382
TI  - Molecular phylogenetics and evolutionary history of the neotropical Satyrine
      Subtribe Euptychiina (Nymphalidae: Satyrinae).
AB  - The Euptychiina is one of the more diverse lineages of satyrine butterflies,
      represented by over 300 species. The first phylogenetic analyses of the subtribe
      is presented based on 2506 aligned nucleotide sequences obtained from 69
      individuals spanning 28 ingroup genera and nine outgroup genera. Two genes were
      used, the mitochondrial gene cytochrome oxidase 1 (1268 bp) and the nuclear gene
      elongation factor-1alpha (1238 bp). The subtribe is never recovered as
      monophyletic in analyses using parsimony, maximum likelihood, or Bayesian
      inference. Several euptychiine genera are placed basal to the ingroup, but
      support is found only for Euptychia and Oressinoma. Three main lineages within
      the ingroup were clearly defined and many taxonomic groupings within the clades
      strongly supported. The majority of genera tested were paraphyletic or
      polyphyletic. Based on results presented here and novel host use, a close
      relationship of Euptychia to the Indo-Australian tribe Ragadiini is hypothesized.
      Origins of the group remain unclear, but the basal position of most of the
      Nearctic genera is discussed.

PMID- 15579383
TI  - An evaluation of support for order-level monophyly and interrelationships within
      the class Demospongiae using partial data from the large subunit rDNA and
      cytochrome oxidase subunit I.
AB  - Large subunit ribosomal DNA (LSU rDNA) sequence data from 120 taxa and cytochrome
      oxidase subunit 1(COI) sequence data from 27 taxa are analyzed separately and
      together to estimate the internal phylogeny of the class Demospongiae and to
      evaluate how consistent these data are with pre-existing hypotheses of
      relationship concerning order-level monophyly and relationships. The monophyly of
      Porifera is only slightly inconsistent with LSU data, which do not support the
      monophyly of the class Demospongiae regardless of the inclusion or exclusion of
      Homoscleromopha (this result is likely due to the placement of a single
      hexactinellid taxon within the Demospongiae), however, no LSU support is found
      for the monophyly of Silicea (Demospongiae+Hexactinellida) unless
      homoscleromorphs are excluded. Neither the subclasses Ceractinomorpha and
      Tetractinomorpha, nor the orders Halichondrida, Hadromerida, and Haplosclerida
      are supported as monophyletic under any data partition. The haplosclerid
      suborders Haplosclerina and Petrosina are supported as monophyletic to the
      exclusion of the suborder Spongillina, and the orders Dictyoceratida, Verongida,
      Poecilosclerida, Astrophorida, Spirophorida, Homosclerophorida, and Agelasida are
      largely reconstructed as monophyletic, with the exception of few anomalously
      placed taxa. Few inter-order relationships are strongly supported by any data
      partition, but there is moderate support for a verongid+chondrosid clade and a
      tetractinellid+halichondrid clade. Furthermore, LSU data strongly support the
      existence of two novel clades that do not correspond to the existing
      classification and that show no morphological uniformity. Finally, every data
      partition supports the monophyly of a clade that includes the order Agelasida,
      some members of the genus Axinella, and two taxa tentatively identified as
      belonging to the orders Hadromerida and Halichondrida.

PMID- 15579384
TI  - Phylogenetic relationships of finches and allies based on nuclear and
      mitochondrial DNA.
AB  - The complete mitochondrial gene cytochrome b in combination with a nuclear gene,
      beta-fibrinogen intron 7, is sequenced for different groups of mostly granivorous
      species in the superfamily Passeroidea, with a focus on the estrildids and
      fringillids. From our study we can conclude that within the group of granivorous
      finches two clades can be distinguished, the estrildid weaver clade and the
      cardueline, fringillid, emberizid, passerine sparrow clade. In contrast to many
      other studies the passerine sparrows are not placed within the weavers estrildid
      clade which is in agreement with other recent studies (e.g., ). Our study also
      shows that the estrildids do form a monophyletic group, but there is a division
      based on geographic origin: an African group and an Asian-Australian group.
      Within the Fringillidae the Fringilla species are the sister group of the
      carduelines.

PMID- 15579385
TI  - Phylogenetic analysis of the genus Thymallus (grayling) based on mtDNA control
      region and ATPase 6 genes, with inferences on control region constraints and
      broad-scale Eurasian phylogeography.
AB  - We present first insights into the molecular phylogeny of the grayling genus
      Thymallus (Salmonidae) using sequences from the mitochondrial control region and
      ATPase6 genes. A suite of analytical approaches were applied for each gene
      separately and for the combined data. The ATPase6 gene is shown to have a mean
      divergence rate across the genus of 2.46 times faster than the complete control
      region. Based on the combined data, four major (internal) clades, presumably
      originating in the Pliocene, were resolved with high support in all analyses and
      represented two distinct lineages in the Amur basin, one lineage in all remaining
      Siberian and Mongolian drainages, and one lineage corresponding to European
      grayling Thymallus thymallus. The resolution of multiple lineages, from both
      additional internal and terminal clades, within each major drainage basin
      underscores the complexity and effects that Pleistocene hydrological dynamics
      have had on the distribution of biodiversity in Siberia.

PMID- 15579386
TI  - Opening the black box: phylogenetics and morphological evolution of the Malagasy
      fossorial lizards of the subfamily "Scincinae".
AB  - The island of Madagascar harbors a highly endemic vertebrate fauna including a
      high diversity of lizards of the subfamily "Scincinae," with about 57 species in
      eight genera. Since limb reduction seems to have been a common phenomenon during
      the evolution of Malagasy "scincines," diagnosing evolutionary relationships
      based on morphology has been difficult. Phylogenetic analyses of multiple
      mitochondrial DNA sequences including the entire ND1, tRNA(LEU), tRNA(ILE),
      tRNA(GLN) genes, and fragments of the 12S and 16S rRNA and tRNA(MET) genes were
      conducted to test the monophyly of the largest genus Amphiglossus, and to
      evaluate the various formal and informal species groupings previously proposed
      for this species-rich group. A further objective was to determine the
      phylogenetic placements of the several greatly limb-reduced and limbless Malagasy
      "scincines" and ascertain whether any of these are derived from within the
      morphologically plesiomorphic Amphiglossus. As limb reduction in skinks is mostly
      associated with body elongation via an increase in the number of presacral
      vertebrae, we evaluate the pattern of evolution of the numbers of presacral
      vertebrae in the context of our phylogeny. We demonstrate that Amphiglossus as
      currently diagnosed is non-monophyletic, and the species fall into two major
      groups. One of these groups is a clade that contains the included species of the
      subgenus Amphiglossus (Madascincus) among other species and is a member of a
      larger clade containing Paracontias and Pseudoacontias. In the second group, the
      nominate subgenus Amphiglossus (Amphiglossus) forms several subclades within a
      larger clade that also contains Androngo crenni and Pygomeles braconnieri, and is
      sister to Voeltzkowia. All analyses provide strong support for the monophyly of
      Paracontias and Voeltzkowia. Based on the preferred phylogenetic hypothesis and
      weighted squared-change parsimony we show that the ancestor of the Malagasy clade
      was already elongated and had a moderately high number of presacral vertebrae (46
      48), which is hypothesized to be the ancestral condition for the whole Malagasy
      "scincine" clade. We further demonstrate that both multiple increases and
      reductions of presacral vertebrae evolved in many clades of Malagasy "scincines"
      and that the use of presacral vertebrae as a major character to diagnose
      supraspecific units is dubious. Based on our results and published morphological
      evidence we consider Scelotes waterloti Angel, 1930 to be a junior synonym of
      Amphiglossus reticulatus (Kaudern, 1922).

PMID- 15579387
TI  - Molecular phylogeny and evolution of the freshwater eels genus Anguilla based on
      the whole mitochondrial genome sequences.
AB  - Molecular phylogenetic analyses were conducted using the whole mitochondrial
      genome sequences of all 18 species/subspecies of the freshwater eels genus
      Anguilla to infer their phylogenetic relationships and to evaluate hypotheses
      about the possible dispersal routes of this genus. The Bayesian and maximum
      likelihood analyses using a total of 15,187 sites of mitochondrial DNA sequences
      suggested that A. mossambica was the most basal species of anguillid eel, and
      that the other species (except for A. borneensis) formed three geographic clades:
      Atlantic (two species), Oceania (three species), and Indo-Pacific (11 species).
      The present study clearly indicated a sister relationship between the Atlantic
      and Oceanian species, which now have distantly separated geographic
      distributions. This suggests that the previous hypotheses to estimate the
      dispersal route of anguillid eels into the Atlantic Ocean based on the current
      geographic distribution of species are unsupported by the present more complete
      analysis. Alternatively, the unique geographic distribution of the present day
      species in the genus Anguilla appears to have resulted from multiple dispersal
      events. Although the age of the beginning of speciation among anguillid eels was
      tentatively estimated as 20 million years ago using a calibration for bony fishes
      of 7.3x10(-4) substitutions/site/million years, it is possible that this
      divergence time was underestimated because of the ecological characteristics of
      these fishes. The results of the present study suggest that the hypotheses for
      the dispersal route and divergence time of the genus Anguilla should be
      reconsidered.

PMID- 15579388
TI  - Phylogenetic analysis of Myriapoda using three nuclear protein-coding genes.
AB  - We assessed the ability of three nuclear protein-encoding genes-elongation factor
      1alpha (EF-1alpha), RNA polymerase II (Pol II), and elongation factor-2 (EF-2)
      from 59 myriapod and 12 non-myriapod species to resolve phylogenetic
      relationships among myriapod classes and orders. In a previous study using EF
      1alpha and Pol II (2134 nt combined) from 34 myriapod taxa, Regier and Shultz
      recovered widely accepted classes, orders, and families but failed to resolve
      interclass and interordinal relationships. The result was attributed to
      heterogenous rates of cladogenesis (specifically, the inability of the slowly
      evolving sequences to capture phylogenetic signal during rapid phylogenetic
      diversification) but the possibility of inadequate taxon sampling or limited
      sequence information could not be excluded. In the present study, the myriapod
      taxon sample was increased by 25 taxa (73%) and sequence length per taxon was
      effectively doubled through addition of EF-2 (4318 nt combined). Parsimony and
      Bayesian analyses of the expanded data set recovered a monophyletic Myriapoda,
      all four myriapod classes and all multiply sampled orders, often with high node
      support. However, except for three diplopod clades (Colobognatha,
      Helminothomorpha, and a subgroup of Pentazonia), few interordinal relationships
      and no interclass relationships were well supported. These results are similar to
      those of the earlier study by Regier and Shultz, which indicates that taxon
      sample and sequence length alone do not readily explain the weakly supported
      resolution in the earlier study. We review recent paleontological evidence to
      further develop our proposal that heterogeneity in phylogenetic signal provided
      by our slowly evolving sequences is due to heterogeneity in the temporal
      structure of myriapod diversification.

PMID- 15579389
TI  - Molecular phylogenetic analysis of mangroves: independent evolutionary origins of
      vivipary and salt secretion.
AB  - The most remarkable morphological specializations of mangroves are vivipary, salt
      secretion, and aerial roots. There has been a long debate on whether the complex
      traits vivipary and secreters have a single origin, the answer to which has
      profound implications for the mechanism of evolution in mangroves. We took a
      large and representative sample across mangroves and sequenced the 18S rRNA,
      rbcL, and matR genes. Together with the outgroups, our data yielded a high
      resolution phylogeny which allowed us to gain much needed insight into the
      distributions of the two characters and address their evolutionary origins. For
      each character, its ancestral state in the phylogeny was estimated by the maximum
      likelihood method. Overall evidence is in favor of a multiple origin for both
      vivipary and salt secretion in mangroves.

PMID- 15579390
TI  - Inferring the phylogenetic position of Boa constrictor among the Boinae.
AB  - Snakes of the subfamily Boinae are found in Madagascar, the Papuan-Pacific
      Islands, and the Neotropics. It has been suggested that genera within each of
      these particular areas do not form monophyletic groups. Further, it was proposed
      that the New World Boa constrictor is more closely related to boine genera in
      Madagascar than to boines in the Neotropics. Along with inferring the
      relationship of all boine genera using data from the cytochrome b gene and
      morphology, the placement of Boa was also examined. Phylogenetic inferences using
      maximum likelihood and Bayesian (BI) methods for combined data analyses and
      separate analyses of DNA sequence and morphological data were conducted. Priors,
      parametric bootstraps, and the Shimodaira-Hasegawa test were used to examine the
      previously proposed placement of Boa with Madagascan taxa using these DNA data.
      DNA data and combined data analyses strongly reject the hypothesis that Boa is
      more closely related to Old World genera than to other New World genera.
      Additionally, strong tree support suggests that all species within Madagascar,
      the Papuan-Pacific Islands, and the Neotropics each form a monophyletic group
      with respect to their geographic region.

PMID- 15579391
TI  - Nuclear and mitochondrial evolutionary analyses of Collared, White-lipped, and
      Chacoan peccaries (Tayassuidae).
AB  - The three extant peccary species, the Chacoan (Catagonus wagneri), the White
      lipped (Tayassu pecari) and the Collared (Pecari tajacu), are morphologically and
      chromosomally distinct and confined to the New World. There is ongoing
      paleontological, cytogenetic, and molecular debate about phylogenetic
      relationships among them. To contribute to the understanding of Tayassuidae
      phylogeny, three mitochondrial (control region, cytochrome b, and 12S rRNA) and
      five nuclear (K-casein, thyrotropin, tyrosinase, and swine short interspersed
      nuclear elements PRE-1 P27 and P642) peccary DNA fragments were amplified, cloned
      and sequenced from Chacoan, White-lipped, and Collared peccaries. Phylogenetic
      analyses were performed using maximum likelihood and neighbor joining methods. K
      casein, thyrotropin, and tyrosinase sequences did not resolve the phylogeny,
      while control region, cytochrome b, 12S rRNA, and PRE-1 P27 and P642 sequences
      were more informative in deciphering phylogenetic relationships. When pig and
      warthog were used as an outgroup, Chacoan and White-lipped peccaries clustered
      distinct from Collared peccaries. Furthermore, control region and cytochrome b
      sequence variation within Collared peccaries was as extreme as that between White
      lipped and Chacoan peccaries, supporting subspecific and possibly even specific
      variation within the widely distributed Collared peccary. This study supports the
      existence of two independent genera within the Tayassuidae family consisting of
      Collared and Chacoan/White-lipped peccaries, in contrast with classical
      morphological taxonomy which clusters White-lipped and Collared peccaries in the
      genus Tayassu or which alternatively clusters the Collared peccary in the genus
      Dicotyles as a related sister clade of the Chacoan peccary (genus Catagonus).

PMID- 15579392
TI  - A mitochondrial phylogeny of the rainforest skink genus Saproscincus, Wells and
      Wellington (1984).
AB  - The phylogenetic relationships and historical biogeography of 10 currently
      described rainforest skinks in the genus Saproscincus were investigated using
      mitochondrial protein-coding ND4 and ribosomal RNA 16S genes. A robust phylogeny
      is inferred using both maximum likelihood and Bayesian analysis, with all inter
      specific nodes strongly supported when datasets are combined. The phylogeny
      supports the recognition of two major lineages (northern and southern), each of
      which comprises two divergent clades. Both northern and southern lineages have
      comparably divergent representatives in mid-east Queensland (MEQ), providing
      further molecular evidence for the importance of two major biogeographic breaks,
      the St. Lawrence gap and Burdekin gap separating MEQ from southern and northern
      counterparts respectively. Vicariance associated with the fragmentation and
      contraction of temperate rainforest during the mid-late Miocene epoch underpins
      the deep divergence between morphologically conservative lineages in at least
      three instances. In contrast, one species, Saproscincus oriarus, shows very low
      sequence divergence but distinct morphological and ecological differentiation
      from its allopatric sister clade within Saproscincus mustelinus. These results
      suggest that while vicariance has played a prominent role in diversification and
      historical biogeography of Saproscincus, divergent selection may also be
      important.

PMID- 15579393
TI  - Strange bayes indeed: uniform topological priors imply non-uniform clade priors.
AB  - While Bayesian analysis has become common in phylogenetics, the effects of
      topological prior probabilities on tree inference have not been investigated. In
      Bayesian analyses, the prior probability of topologies is almost always
      considered equal for all possible trees, and clade support is calculated from the
      majority rule consensus of the approximated posterior distribution of topologies.
      These uniform priors on tree topologies imply non-uniform prior probabilities of
      clades, which are dependent on the number of taxa in a clade as well as the
      number of taxa in the analysis. As such, uniform topological priors do not model
      ignorance with respect to clades. Here, we demonstrate that Bayesian clade
      support, bootstrap support, and jackknife support from 17 empirical studies are
      significantly and positively correlated with non-uniform clade priors resulting
      from uniform topological priors. Further, we demonstrate that this effect
      disappears for bootstrap and jackknife when data sets are free from character
      conflict, but remains pronounced for Bayesian clade supports, regardless of tree
      shape. Finally, we propose the use of a Bayes factor to account for the fact that
      uniform topological priors do not model ignorance with respect to clade
      probability.

PMID- 15579394
TI  - Phylogenetic and phylogeographic relationships in the crayfish genus
      Austropotamobius inferred from mitochondrial COI gene sequences.
AB  - The present study explores the utility of mitochondrial COI gene sequences to
      reveal phylogenetic and phylogeographic relationships for the entire European
      freshwater crayfish genus Austropotamobius. The two traditional taxa,
      Austropotamobius pallipes and Austropotamobius torrentium, were monophyletic,
      showing similar genetic diversity, with 28 and 25 haplotypes, respectively, and
      an uncorrected average pairwise divergence of 0.059 and 0.041. A third distinct
      haplotype clade, in sister relation to A. torrentium, was discovered at the Upper
      Kolpa drainage in the northern Dinaric area. All populations north and west of
      the Alps are genetically impoverished (nucleotide diversity (pi)=0.000-0.001),
      while southern populations are more diverse (pi=0.001-0.034). A. pallipes reaches
      the highest diversity in the region of Istra, probably its primary center of
      radiation. The genetic diversity center for A. torrentium is the southern Balkan
      peninsula. Other potential glacial refugia were identified in Southern France,
      Northwestern Italy, the Apennine Peninsula, and in the northern Dinaric area. The
      Iberian Peninsula has been stocked artificially from Northern Italy. Three main
      periods of radiation were tentatively identified: late Miocene/early Pliocene for
      the divergence of species and main lineages, the Pleistocene for the divergence
      within populations south from Alps, and a postPleistocene expansion north and
      west from Alps.

PMID- 15579395
TI  - Molecular phylogeny and evidence for an adaptive radiation of geophagine cichlids
      from South America (Perciformes: Labroidei).
AB  - Nucleotide sequences from the mitochondrial ND4 gene and the nuclear RAG2 gene
      were used to derive the most extensive molecular phylogeny to date for the
      Neotropical cichlid subfamily Geophaginae. Previous hypotheses of relationships
      were tested in light of these new data and a synthesis of all existing molecular
      information was provided. Novel phylogenetic findings included support for : (1)
      a 'Big Clade' containing the genera Geophagus sensu lato, Gymnogeophagus,
      Mikrogeophagus, Biotodoma, Crenicara, and Dicrossus; (2) a clade including the
      genera Satanoperca, Apistogramma, Apistogrammoides, and Taeniacara; and (3)
      corroboration for Kullander's clade Acarichthyini. ND4 demonstrated saturation
      effects at the third code position and lineage-specific rate heterogeneity, both
      of which influenced phylogeny reconstruction when only equal weighted parsimony
      was employed. Both branch lengths and internal branch tests revealed extremely
      short basal nodes that add support to the idea that geophagine cichlids have
      experienced an adaptive radiation sensu Schluter that involved ecomorphological
      specializations and life history diversification.

PMID- 15579396
TI  - Is environmental health a basic human right?

PMID- 15579398
TI  - The legacy of conflicts.

PMID- 15579399
TI  - U.S. PBDE levels: effects in mice.

PMID- 15579400
TI  - Mercury levels in mothers.

PMID- 15579401
TI  - The human population: accepting earth's limitations.

PMID- 15579403
TI  - Conflicts of interests: declarations for all.

PMID- 15579404
TI  - NRDC knocks nukes.

PMID- 15579405
TI  - Symposium explores children's environments.

PMID- 15579406
TI  - Battle scars: global conflicts and environmental health.

PMID- 15579407
TI  - Environmental health disparities: a framework integrating psychosocial and
      environmental concepts.
AB  - Although it is often acknowledged that social and environmental factors interact
      to produce racial and ethnic environmental health disparities, it is still
      unclear how this occurs. Despite continued controversy, the environmental justice
      movement has provided some insight by suggesting that disadvantaged communities
      face greater likelihood of exposure to ambient hazards. The exposure-disease
      paradigm has long suggested that differential "vulnerability" may modify the
      effects of toxicants on biological systems. However, relatively little work has
      been done to specify whether racial and ethnic minorities may have greater
      vulnerability than do majority populations and, further, what these
      vulnerabilities may be. We suggest that psychosocial stress may be the
      vulnerability factor that links social conditions with environmental hazards.
      Psychosocial stress can lead to acute and chronic changes in the functioning of
      body systems (e.g., immune) and also lead directly to illness. In this article we
      present a multidisciplinary framework integrating these ideas. We also argue that
      residential segregation leads to differential experiences of community stress,
      exposure to pollutants, and access to community resources. When not
      counterbalanced by resources, stressors may lead to heightened vulnerability to
      environmental hazards.

PMID- 15579408
TI  - Sex and ceruloplasmin modulate the response to copper exposure in healthy
      individuals.
AB  - Previous studies indicated that sex might influence the response to copper
      exposure. Ceruloplasmin (Cp) is an indicator of Cu status, but it is not clear
      whether and how it reflects changes of Cu status among healthy individuals. In
      this study, 82 apparently healthy women and men were chosen from 800 individuals
      because their Cp values belonged to the higher and lower 10% of the group Cp
      distribution curve. Before and after receiving a supplement of 10mg Cu/day (upper
      limit of daily intake) for 2 months, we performed blood and urinary biochemical
      measurement of potential Cu markers. We used principal component analysis and
      linear discriminant analysis to identify blood and/or urinary Cu indicators that
      showed a differential response to copper. Results showed that Cp values in serum
      represent a reliable indicator to differentiate subgroups within the normal
      population in their response to Cu exposure. The response depends on Cp values
      and on sex, such that women with higher and men with lower Cp values exhibit the
      greatest response.

PMID- 15579409
TI  - Synergistic embryotoxicity of polycyclic aromatic hydrocarbon aryl hydrocarbon
      receptor agonists with cytochrome P4501A inhibitors in Fundulus heteroclitus.
AB  - Widespread contamination of aquatic systems with polycyclic aromatic hydrocarbons
      (PAHs) has led to concern about effects of PAHs on aquatic life. Some PAHs have
      been shown to cause deformities in early life stages of fish that resemble those
      elicited by planar halogenated aromatic hydrocarbons (pHAHs) that are agonists
      for the aryl hydrocarbon receptor (AHR). Previous studies have suggested that
      activity of cytochrome P4501A, a member of the AHR gene battery, is important to
      the toxicity of pHAHs, and inhibition of CYP1A can reduce the early-life-stage
      toxicity of pHAHs. In light of the effects of CYP1A inhibition on pHAH-derived
      toxicity, we explored the impact of both model and environmentally relevant CYP1A
      inhibitors on PAH-derived embryotoxicity. We exposed Fundulus heteroclitus
      embryos to two PAH-type AHR agonists, ss-naphthoflavone and benzo(a)pyrene, and
      one pHAH-type AHR agonist, 3,3 ,4,4 ,5-pentachlorobiphenyl (PCB-126), alone and
      in combination with several CYP1A inhibitors. In agreement with previous studies,
      coexposure of embryos to PCB-126 with the AHR antagonist and CYP1A inhibitor
      alpha-naphthoflavone decreased frequency and severity of deformities compared
      with embryos exposed to PCB-126 alone. In contrast, embryos coexposed to the PAHs
      with each of the CYP1A inhibitors tested were deformed with increased severity
      and frequency compared with embryos dosed with PAH alone. The mechanism by which
      inhibition of CYP1A increased embryotoxicity of the PAHs tested is not
      understood, but these results may be helpful in elucidating mechanisms by which
      PAHs are embryotoxic. Additionally, these results call into question additive
      models of PAH embryotoxicity for environmental PAH mixtures that contain both AHR
      agonists and CYP1A inhibitors.

PMID- 15579410
TI  - The relationship of urinary metabolites of carbaryl/naphthalene and chlorpyrifos
      with human semen quality.
AB  - Most of the general population is exposed to carbaryl and other contemporary-use
      insecticides at low levels. Studies of laboratory animals, in addition to limited
      human data, show an association between carbaryl exposure and decreased semen
      quality. In the present study we explored whether environmental exposures to 1
      naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2
      pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are
      associated with decreased semen quality in humans. Subjects (n=272) were
      recruited through a Massachusetts infertility clinic. Individual exposures were
      measured as spot urinary concentrations of 1N and TCPY adjusted using specific
      gravity. Semen quality was assessed as sperm concentration, percent motile sperm,
      and percent sperm with normal morphology, along with sperm motion parameters
      (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N
      concentrations were 3.22 and 3.19microg/L, respectively. For increasing 1N
      tertiles, adjusted odds ratios (ORs) were significantly elevated for below
      reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2,
      4.2, respectively; p-value for trend =0.01) and percent motile sperm (1.0, 2.5,
      2.4; p-value for trend = 0.01). The sperm motion parameter most strongly
      associated with 1N was straight-line velocity. There were suggestive, borderline
      significant associations for TCPY with sperm concentration and motility, whereas
      sperm morphology was weakly and nonsignificantly associated with both TCPY and
      1N. The observed associations between altered semen quality and 1N are consistent
      with previous studies of carbaryl exposure, although suggestive associations with
      TCPY are difficult to interpret because human and animal data are currently
      limited.

PMID- 15579411
TI  - Effects of loud noise exposure on DNA integrity in rat adrenal gland.
AB  - Loud noise is generally considered an environmental stressor causing negative
      effects on acoustic, cardiovascular, nervous, and endocrine systems. In this
      study, we investigated the effects of noise exposure on DNA integrity in rat
      adrenal gland evaluated by the comet assay. The exposure to loud noise (100 dBA)
      for 12 hr caused a significant increase of DNA damage in the adrenal gland.
      Genetic alterations did not decrease 24 hr after the cessation of the stimulus.
      We hypothesize that an imbalance of redox cell status is responsible for the
      induction and persistence of noise-induced cellular damage.

PMID- 15579412
TI  - Prospective study of blood and tibia lead in women undergoing surgical menopause.
AB  - Despite the dramatic decline in environmental lead exposure in the United States
      during the past couple of decades, concern has been expressed regarding
      mobilization during menopause of existing lead stored in bone. To investigate
      whether bone lead concentrations decrease and blood lead levels increase, we
      conducted a prospective study of 91 women who were scheduled to undergo a
      bilateral oophorectomy for a benign condition at Mount Sinai Hospital in New York
      City during October 1994 through April 1999. We excluded women who were younger
      than 30 years of age or who were postmenopausal at the time of the surgery. We
      observed a small but significant increase in median blood lead levels between the
      baseline visit and the 6-month visit (0.4 microg/dL, p<0.0001), particularly for
      women who were not on estrogen replacement therapy (0.7 microg/dL, p=0.008). No
      significant change was observed in blood lead values between 6 and 18 months
      postsurgery, nor was there evidence of significant changes in tibia lead
      concentrations during the follow-up period. These findings do not point to
      substantial mobilization of lead from cortical bone during menopause.

PMID- 15579413
TI  - The sources of inflammatory mediators in the lung after silica exposure.
AB  - The expression of 10 genes implicated in regulation of the inflammatory processes
      in the lung was studied after exposure of alveolar macrophages (AMs) to silica in
      vitro or in vivo. Exposure of AMs to silica in vitro up-regulated the messenger
      RNA (mRNA) levels of three genes [interleukin-6 (IL-6), monocyte chemoattractant
      protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2)] without a
      concomitant increase in the protein levels. AMs isolated after intratracheal
      instillation of silica up-regulated mRNA levels of four additional genes
      [granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-1beta, IL-10, and
      inducible nitric oxide synthase]. IL-6, MCP-1, and MIP-2 protein levels were
      elevated in bronchoalveolar lavage fluid. Fibroblasts under basal culture
      conditions express much higher levels of IL-6 and GM-CSF compared with AMs.
      Coculture of AMs and alveolar type II cells, or coculture of AMs and lung
      fibroblasts, in contact cultures or Transwell chambers, revealed no synergistic
      effect. Therefore, such interaction does not explain the effects seen in vivo.
      Identification of the intercellular communication in vivo is still unresolved.
      However, fibroblasts appear to be an important source of inflammatory mediators
      in the lung.

PMID- 15579414
TI  - Estimating the independent effects of multiple pollutants in the presence of
      measurement error: an application of a measurement-error-resistant technique.
AB  - Misclassification of exposure usually leads to biased estimates of exposure
      response associations. This is particularly an issue in cases with multiple
      correlated exposures, where the direction of bias is uncertain. It is necessary
      to address this problem when considering associations with important public
      health implications such as the one between mortality and air pollution, because
      biased exposure effects can result in biased risk assessments. The National
      Morbidity and Mortality Air Pollution Study (NMMAPS) recently reported results
      from an assessment of multiple pollutants and daily mortality in 90 U.S. cities.
      That study assessed the independent associations of the selected pollutants with
      daily mortality in two-pollutant models. Excess mortality was associated with
      particulate matter of aerodynamic diameter less than or equal to 10 microm/m3
      (PM10), but not with other pollutants, in these two pollutant models. The extent
      of bias due to measurement error in these reported results is unclear. Schwartz
      and Coull recently proposed a method that deals with multiple exposures and,
      under certain conditions, is resistant to measurement error. We applied this
      method to reanalyze the data from NMMAPS. For PM10, we found results similar to
      those reported previously from NMMAPS (0.24% increase in deaths per 10-microg/m3)
      increase in PM10). In addition, we report an important effect of carbon monoxide
      that had not been observed previously.

PMID- 15579415
TI  - Epidemiologic evaluation of measurement data in the presence of detection limits.
AB  - Quantitative measurements of environmental factors greatly improve the quality of
      epidemiologic studies but can pose challenges because of the presence of upper or
      lower detection limits or interfering compounds, which do not allow for precise
      measured values. We consider the regression of an environmental measurement
      (dependent variable) on several covariates (independent variables). Various
      strategies are commonly employed to impute values for interval-measured data,
      including assignment of one-half the detection limit to nondetected values or of
      "fill-in" values randomly selected from an appropriate distribution. On the basis
      of a limited simulation study, we found that the former approach can be biased
      unless the percentage of measurements below detection limits is small (5-10%).
      The fill-in approach generally produces unbiased parameter estimates but may
      produce biased variance estimates and thereby distort inference when 30% or more
      of the data are below detection limits. Truncated data methods (e.g., Tobit
      regression) and multiple imputation offer two unbiased approaches for analyzing
      measurement data with detection limits. If interest resides solely on regression
      parameters, then Tobit regression can be used. If individualized values for
      measurements below detection limits are needed for additional analysis, such as
      relative risk regression or graphical display, then multiple imputation produces
      unbiased estimates and nominal confidence intervals unless the proportion of
      missing data is extreme. We illustrate various approaches using measurements of
      pesticide residues in carpet dust in control subjects from a case-control study
      of non-Hodgkin lymphoma.

PMID- 15579416
TI  - Use of pharmacokinetic modeling to design studies for pathway-specific exposure
      model evaluation.
AB  - Validating an exposure pathway model is difficult because the biomarker, which is
      often used to evaluate the model prediction, is an integrated measure for
      exposures from all the exposure routes and pathways. The purpose of this article
      is to demonstrate a method to use pharmacokinetic (PK) modeling and computer
      simulation to guide the design of field studies to validate pathway models. The
      children's dietary intake model is discussed in detail as an example. Three
      important aspects are identified for a successful design to evaluate the
      children's dietary intake model: a) longitudinally designed study with
      significant changes in the exposure for the route/pathway of interest, b) short
      biologic half-life of the selected chemical, and c) surface loading of the
      selected chemical at sufficient levels. Using PK modeling to guide a study design
      allowed a path-specific exposure model to be evaluated using urinary metabolite
      biomarkers.

PMID- 15579417
TI  - Association of chromosomal alterations with arsenite-induced tumorigenicity of
      human HaCaT keratinocytes in nude mice.
AB  - Inorganic arsenic is a well-documented human carcinogen. Chronic low-dose
      exposure to inorganic arsenic is associated with an increased incidence of a
      variety of cancers, including skin, lung, bladder, and liver cancer. Because
      genetic alterations often occur during cancer development, the objective of this
      study was to explore what types of genetic alterations were induced by chronic
      exposure of human HaCaT cells to arsenic. After 20 passages in the presence of
      inorganic trivalent arsenite at concentrations of 0.5 or 1 microM, HaCaT cells
      had higher intracellular levels of glutathione, became more resistance to
      arsenite, and showed an increased frequency of micronuclei. Furthermore, the
      previously nontumorigenic HaCaT cells became tumorigenic, as shown by
      subcutaneous injection into Balb/c nude mice. Cell lines derived from the tumors
      formed by injection of arsenite-exposed HaCaT cells into nude mice expressed
      higher levels of keratin 6, a proliferation marker of keratinocytes, than did
      parental HaCaT cells, whereas the expression of keratins 5, 8, and 10 was
      significantly decreased. Comparative genomic hybridization demonstrated
      chromosomal alterations in the 11 cell lines derived from these tumors; all 11
      showed significant loss of chromosome 9q, and seven showed significant gain of
      chromosome 4q. The present results show that long-term exposure to low doses of
      arsenite transformed nontumorigenic human keratinocytes to cells that were
      tumorigenic in nude mice and that chromosomal alterations were observed in all
      cell lines established from the tumors.

PMID- 15579418
TI  - Is bone mineral composition disrupted by organochlorines in east Greenland polar
      bears (Ursus maritimus)?
AB  - We analyzed bone mineral density (BMD) in skulls of polar bears (Ursus maritimus)
      (n = 139) from East Greenland sampled during 1892-2002. Our primary goal was to
      detect possible changes in bone mineral content (osteopenia) due to elevated
      exposure to organochlorine [polychlorinated biphenyls (PCBs), dichlorodiphenyl
      trichloroethane (DDT) and its metabolites, chlordanes (CHLs), dieldrin,
      hexacyclohexanes, hexachlorobenzene] and polybrominated diphenyl ether (PBDE)
      compounds. To ensure that the BMD value in skull represented the mineral status
      of the skeletal system in general, we compared BMD values in femur and three
      lumbar vertebrae with skull in a subsample. We detected highly significant
      correlations between BMD in skull and femur (r = 0.99; p < 0.001; n = 13) and
      skull and vertebrae (r = 0.97; p < 0.001; n = 8). BMD in skulls sampled in the
      supposed pre-organochlorine/PBDE period (1892-1932) was significantly higher than
      that in skulls sampled in the supposed pollution period (1966-2002) for subadult
      females, subadult males, and adult males (all, p < 0.05) but not adult females (p
      = 0.94). We found a negative correlation between organochlorines and skull BMD
      for the sum of PCBs (SigmaPCB; p < 0.04) and SigmaCHL (p < 0.03) in subadults and
      for dieldrin (p < 0.002) and SigmaDDT (p < 0.02) in adult males; indications for
      SigmaPBDE in subadults were also found (p = 0.06). In conclusion, the strong
      correlative relationships suggest that disruption of the bone mineral composition
      in East Greenland polar bears may have been caused by organochlorine exposure.

PMID- 15579419
TI  - GIS modeling of air toxics releases from TRI-reporting and non-TRI-reporting
      facilities: impacts for environmental justice.
AB  - The Toxics Release Inventory (TRI) requires facilities with 10 or more full-time
      employees that process > 25,000 pounds in aggregate or use > 10,000 pounds of any
      one TRI chemical to report releases annually. However, little is known about
      releases from non-TRI-reporting facilities, nor has attention been given to the
      very localized equity impacts associated with air toxics releases. Using
      geographic information systems and industrial source complex dispersion modeling,
      we developed methods for characterizing air releases from TRI-reporting as well
      as non-TRI-reporting facilities at four levels of geographic resolution. We
      characterized the spatial distribution and concentration of air releases from one
      representative industry in Durham County, North Carolina (USA). Inclusive
      modeling of all facilities rather than modeling of TRI sites alone significantly
      alters the magnitude and spatial distribution of modeled air concentrations.
      Modeling exposure receptors at more refined levels of geographic resolution
      reveals localized, neighborhood-level exposure hot spots that are not apparent at
      coarser geographic scales. Multivariate analysis indicates that inclusive
      facility modeling at fine levels of geographic resolution reveals exposure
      disparities by income and race. These new methods significantly enhance the
      ability to model air toxics, perform equity analysis, and clarify conflicts in
      the literature regarding environmental justice findings. This work has
      substantial implications for how to structure TRI reporting requirements, as well
      as methods and types of analysis that will successfully elucidate the spatial
      distribution of exposure potentials across geographic, income, and racial lines.

PMID- 15579420
TI  - Long-term exposure to environmental concentrations of the pharmaceutical
      ethynylestradiol causes reproductive failure in fish.
AB  - Heightened concern over endocrine-disrupting chemicals is driven by the
      hypothesis that they could reduce reproductive success and affect wildlife
      populations, but there is little evidence for this expectation. The
      pharmaceutical ethynylestradiol (EE2) is a potent endocrine modulator and is
      present in the aquatic environment at biologically active concentrations. To
      investigate impacts on reproductive success and mechanisms of disruption, we
      exposed breeding populations (n = 12) of zebrafish (Danio rerio) over multiple
      generations to environmentally relevant concentrations of EE2. Life-long exposure
      to 5 ng/L EE2 in the F1 generation caused a 56% reduction in fecundity and
      complete population failure with no fertilization. Conversely, the same level of
      exposure for up to 40 days in mature adults in the parental F0 generation had no
      impact on reproductive success. Infertility in the F1 generation after life-long
      exposure to 5 ng/L EE2 was due to disturbed sexual differentiation, with males
      having no functional testes and either undifferentiated or intersex gonads. These
      F1 males also showed a reduced vitellogenic response when compared with F0 males,
      indicating an acclimation to EE2 exposure. Depuration studies found only a
      partial recovery in reproductive capacity after 5 months. Significantly, even
      though the F1 males lacked functional testes, they showed male-pattern
      reproductive behavior, inducing the spawning act and competing with healthy males
      to disrupt fertilization. Endocrine disruption is therefore likely to affect
      breeding dynamics and reproductive success in group-spawning fish. Our findings
      raise major concerns about the population-level impacts for wildlife of long-term
      exposure to low concentrations of estrogenic endocrine disruptors.

PMID- 15579421
TI  - Temporal variability of urinary phthalate metabolite levels in men of
      reproductive age.
AB  - Phthalates are a family of multifunctional chemicals widely used in personal care
      and other consumer products. The ubiquitous use of phthalates results in human
      exposure through multiple sources and routes, including dietary ingestion, dermal
      absorption, inhalation, and parenteral exposure from medical devices containing
      phthalates. We explored the temporal variability over 3 months in urinary
      phthalate metabolite levels among 11 men who collected up to nine urine samples
      each during this time period. Eight phthalate metabolites were measured by solid
      phase extraction-high-performance liquid chromatography-tandem mass spectrometry.
      Statistical analyses were performed to determine the between- and within-subject
      variance apportionment, and the sensitivity and specificity of a single urine
      sample to classify a subject's 3-month average exposure. Five of the eight
      phthalates were frequently detected. Monoethyl phthalate (MEP) was detected in
      100% of samples; monobutyl phthalate, monobenzyl phthalate, mono-2-ethylhexyl
      phthalate (MEHP), and monomethyl phthalate were detected in > 90% of samples.
      Although we found both substantial day-to-day and month-to-month variability in
      each individual's urinary phthalate metabolite levels, a single urine sample was
      moderately predictive of each subject's exposure over 3 months. The sensitivities
      ranged from 0.56 to 0.74. Both the degree of between- and within-subject variance
      and the predictive ability of a single urine sample differed among phthalate
      metabolites. In particular, a single urine sample was most predictive for MEP and
      least predictive for MEHP. These results suggest that the most efficient exposure
      assessment strategy for a particular study may depend on the phthalates of
      interest.

PMID- 15579422
TI  - Epidemiology of health effects of radiofrequency exposure.
AB  - We have undertaken a comprehensive review of epidemiologic studies about the
      effects of radiofrequency fields (RFs) on human health in order to summarize the
      current state of knowledge, explain the methodologic issues that are involved,
      and aid in the planning of future studies. There have been a large number of
      occupational studies over several decades, particularly on cancer, cardiovascular
      disease, adverse reproductive outcome, and cataract, in relation to RF exposure.
      More recently, there have been studies of residential exposure, mainly from radio
      and television transmitters, and especially focusing on leukemia. There have also
      been studies of mobile telephone users, particularly on brain tumors and less
      often on other cancers and on symptoms. Results of these studies to date give no
      consistent or convincing evidence of a causal relation between RF exposure and
      any adverse health effect. On the other hand, the studies have too many
      deficiencies to rule out an association. A key concern across all studies is the
      quality of assessment of RF exposure. Despite the ubiquity of new technologies
      using RFs, little is known about population exposure from RF sources and even
      less about the relative importance of different sources. Other cautions are that
      mobile phone studies to date have been able to address only relatively short lag
      periods, that almost no data are available on the consequences of childhood
      exposure, and that published data largely concentrate on a small number of
      outcomes, especially brain tumor and leukemia.

PMID- 15579423
TI  - Incorporating environmental health into pediatric medical and nursing education.
AB  - Pediatric medical and nursing education currently lacks the environmental health
      content necessary to appropriately prepare pediatric health care professionals to
      prevent, recognize, manage, and treat environmental-exposure-related disease.
      Leading health institutions have recognized the need for improvements in health
      professionals' environmental health education. Parents are seeking answers about
      the impact of environmental toxicants on their children. Given the biologic,
      psychological, and social differences between children and adults, there is a
      need for environmental health education specific to children. The National
      Environmental Education and Training Foundation, in partnership with the
      Children's Environmental Health Network, created two working groups, one with
      expertise in medical education and one with expertise in nursing education. The
      working groups reviewed the transition from undergraduate student to professional
      to assess where in those processes pediatric environmental health could be
      emphasized. The medical education working group recommended increasing education
      about children's environmental health in the medical school curricula, in
      residency training, and in continuing medical education. The group also
      recommended the expansion of fellowship training in children's environmental
      health. Similarly, the nursing working group recommended increasing children's
      environmental health content at the undergraduate, graduate, and continuing
      nursing education levels. Working groups also identified the key medical and
      nursing organizations that would be important in leveraging these changes. A
      concerted effort to prioritize pediatric environmental health by governmental
      organizations and foundations is essential in providing the resources and
      expertise to set policy and provide the tools for teaching pediatric
      environmental health to health care providers.

PMID- 15579424
TI  - Prenatal DDT exposure in relation to anthropometric and pubertal measures in
      adolescent males.
AB  - DDT (dichlorodiphenyltrichloroethane), a pesticide once used widely in
      agriculture and now limited to public health use, remains a controversial
      chemical because of a combination of benefits and risks. DDT or its breakdown
      products are ubiquitous in the environment and in humans. Compounds in the DDT
      family have endocrine actions and have been associated with reproductive
      toxicity. A previous study reported associations between prenatal exposure to p,p
      -DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene] and increased height and
      weight in adolescent boys. We examined a group with higher exposures to see
      whether similar associations would occur. Our study group was 304 males born in
      Philadelphia in the early 1960s who had participated in a previous study.
      Anthropometric and pubertal measures from one to six visits during their
      adolescent years were available, as were stored maternal serum samples from
      pregnancy. We measured p,p -DDE, p,p -DDT [1,1,1-trichloro-2,2-bis(p
      chlorophenyl)-ethane], and o,p -DDT [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p
      chlorophenyl)-ethane] in the maternal serum. Outcomes examined in the boys were
      height, ratio of sitting height to height, body mass index, triceps skinfold
      thickness, ratio of subscapular to the sum of triceps and subscapular skinfold
      thicknesses, skeletal age, serum testosterone, and serum dehydroepiandrosterone
      sulfate. No associations between prenatal exposure to any of the DDT compounds
      and any outcome measure were seen.

PMID- 15579425
TI  - Pulmonary epithelial integrity in children: relationship to ambient ozone
      exposure and swimming pool attendance.
AB  - Airway irritants such as ozone are known to impair lung function and induce
      airway inflammation. Clara cell protein (CC16) is a small anti-inflammatory
      protein secreted by the nonciliated bronchiolar Clara cells. CC16 in serum has
      been proposed as a noninvasive and sensitive marker of lung epithelial injury. In
      this study, we used lung function and serum CC16 concentration to examine the
      pulmonary responses to ambient O3 exposure and swimming pool attendance. The
      measurements were made on 57 children 10-11 years of age before and after outdoor
      exercise for 2 hr. Individual O3 exposure was estimated as the total exposure
      dose between 0700 hr until the second blood sample was obtained (mean O3
      concentration/m3 times symbol hours). The maximal 1-hr value was 118 microg/m3
      (59 ppb), and the individual exposure dose ranged between 352 and 914
      microg/m3hr. These O3 levels did not cause any significant changes in mean serum
      CC16 concentrations before or after outdoor exercise, nor was any decrease in
      lung function detected. However, children who regularly visited chlorinated
      indoor swimming pools had significantly lower CC16 levels in serum than did
      nonswimming children both before and after exercise (respectively, 57 +/- 2.4 and
      53 +/- 1.7 microg/L vs. 8.2 +/- 2.8 and 8.0 +/- 2.6 microg/L; p < 0.002). These
      results indicate that repeated exposure to chlorination by-products in the air of
      indoor swimming pools has adverse effects on the Clara cell function in children.
      A possible relation between such damage to Clara cells and pulmonary morbidity
      (e.g., asthma) should be further investigated.

PMID- 15579426
TI  - The effects of the World Trade Center event on birth outcomes among term
      deliveries at three lower Manhattan hospitals.
AB  - The effects of prenatal exposure to pollutants from the World Trade Center (WTC)
      disaster on fetal growth and subsequent health and development of exposed
      children remain a source of concern. We assessed the impact of gestational timing
      of the disaster and distance from the WTC in the 4 weeks after 11 September on
      the birth outcomes of 300 nonsmoking women who were pregnant at the time of the
      event. They were recruited at delivery between December 2001 and June 2002 from
      three hospitals close to the WTC site. Residential and work addresses of all
      participants for each of the 4 weeks after 11 September 2001 were geocoded for
      classification by place and timing of exposure. Average daily hours spent at each
      location were based on the women's reports for each week. Biomedical pregnancy
      and delivery data extracted from the medical records of each mother and newborn
      included medical complications, type of delivery, length of gestation, birth
      weight, birth length, and head circumference. Term infants born to women who were
      pregnant on 11 September 2001 and who were living within a 2-mile radius of the
      WTC during the month after the event showed significant decrements in term birth
      weight (-149 g) and birth length (-0.82 cm), compared with infants born to the
      other pregnant women studied, after controlling for sociodemographic and
      biomedical risk factors. The decrements remained significant with adjustment for
      gestational duration (-122 g and -0.74 cm, respectively). Women in the first
      trimester of pregnancy at the time of the WTC event delivered infants with
      significantly shorter gestation (-3.6 days) and a smaller head circumference (
      0.48 cm), compared with women at later stages of pregnancy, regardless of the
      distance of their residence or work sites from the WTC. The observed adverse
      effects suggest an impact of pollutants and/or stress related to the WTC disaster
      and have implications for the health and development of exposed children.

PMID- 15579427
TI  - Feedback.
AB  - The emergency department provides a rich environment for diverse patient
      encounters, rapid clinical decision making, and opportunities to hone procedural
      skills. Well-prepared faculty can utilize this environment to teach residents and
      medical students and gain institutional recognition for their incomparable role
      and teamwork. Giving effective feedback is an essential skill for all teaching
      faculty. Feedback is ongoing appraisal of performance based on direct observation
      aimed at changing or sustaining a behavior. Tips from the literature and the
      author's experience are reviewed to provide formats for feedback, review of
      objectives, and elements of professionalism and how to deal with poorly
      performing students. Although the following examples pertain to medical student
      education, these techniques are applicable to the education of all adult
      learners, including residents and colleagues. Specific examples of redirection
      and reflection are offered, and pitfalls are reviewed. Suggestions for
      streamlining verbal and written feedback and obtaining feedback from others in a
      fast-paced environment are given. Ideas for further individual and group faculty
      development are presented.

PMID- 15579428
TI  - Teaching evidence-based medicine to medical students.
AB  - Evidence-based medicine (EBM) is the rubric for an approach to learning and
      practicing medicine that applies skills from clinical epidemiology, library
      science, and information management to clinical practice. Teaching EBM
      effectively requires a longitudinal approach throughout medical education. This
      presents many opportunities for academic emergency physicians, especially in the
      setting of an emergency medicine clerkship. EBM is best taught at the bedside,
      although this depends on a skilled and interested faculty. Bedside teaching of
      EBM also requires ready access to modern information resources. Other venues for
      teaching EBM include morning report, teaching conferences, and journal clubs.
      Many tools can be used to aid the process, including Web-based sources such as
      UpToDate, textbooks, and Web-based tutorials, educational prescriptions, and
      critically appraised topics.

PMID- 15579429
TI  - CD18 deficiency protects against multiple low-dose streptozotocin-induced
      diabetes.
AB  - Leukocyte recruitment into pancreatic islets is believed to play an important
      pathophysiological role in autoimmune diabetes. Previous reports have suggested
      that several different adhesion molecules may be involved in leukocyte
      recruitment during autoimmune diabetes, including members of the leukocyte
      beta(2) integrins. Here we report that a gene-targeted deficiency of the beta(2)
      integrin, CD18, protects against multiple low-dose streptozotocin-induced
      autoimmune diabetes. CD18 null mice displayed lower blood glucose values
      throughout the study, with only 10% of these mice eventually developing diabetes
      compared to 95% in the control group. Importantly, the development of insulitis
      was markedly absent in the CD18 null mice, suggesting that members of this
      integrin subfamily predominately regulate leukocyte infiltration into pancreatic
      islets. This study demonstrates that the beta(2) integrins play a key
      pathophysiological role in the development of multiple low-dose streptozotocin
      induced autoimmune diabetes.

PMID- 15579430
TI  - Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic
      cells in metastatic tumor lesions.
AB  - CD1 molecules are expressed by antigen-presenting cells such as dendritic cells
      and mediate primary immune responses to lipids and glycolipids which have been
      shown to be expressed by various tumors. Glycolipids are expressed by melanoma
      cells but, despite their immunogenicity, no efficient spontaneous immune
      responses are elicited. As IL-10 has previously been shown to down-regulate CD1a
      on dendritic cells and is known to be expressed by various melanoma cell lines,
      we investigated if melanoma-derived IL-10 could down-regulate CD1 molecule
      expression on dendritic cells as a possible way to circumvent immune recognition.
      We found that CD1a, CD1b, CD1c, and CD1d were significantly down-regulated on
      dendritic cells in metastatic (n = 10) but not in primary melanoma lesions (n =
      10). We further detected significantly higher IL-10 protein levels in metastatic
      than in primary melanomas. Moreover, supernatants from metastatic melanomas were
      significantly more effective in down-regulating CD1 molecules on dendritic cells
      than supernatants from primary melanoma cultures. This effect was blocked using a
      neutralizing IL-10 antibody in a dose dependent manner. Our findings suggest that
      metastatic but not primary melanomas can down-regulate CD1 molecules on
      infiltrating dendritic cells by secreting IL-10 which may represent a novel way
      to escape the immune response directed against the tumor.

PMID- 15579431
TI  - Minodronate, a newly developed nitrogen-containing bisphosphonate, suppresses
      melanoma growth and improves survival in nude mice by blocking vascular
      endothelial growth factor signaling.
AB  - Angiogenesis, a process by which new vascular networks are formed from pre
      existing capillaries, is required for tumors to grow, invade, and metastasize.
      Vascular endothelial growth factor (VEGF), a specific mitogen to endothelial
      cells, is a crucial factor for tumor angiogenesis. In this study, we investigated
      whether minodronate, a newly developed nitrogen-containing bisphosphonate, could
      inhibit melanoma growth and improve survival in nude mice by suppressing the VEGF
      signaling. We found here that minodronate inhibited melanoma growth and improved
      survival in nude mice by suppressing the tumor-associated angiogenesis and
      macrophage infiltration. Minodronate completely inhibited the VEGF-induced
      increase in DNA synthesis and tube formation in endothelial cells by suppressing
      NADPH oxidase-mediated reactive oxygen species generation and Ras activation.
      Furthermore, minodronate inhibited the VEGF-induced expression of intercellular
      adhesion molecule-1 and monocyte chemoattractant protein-1 in endothelial cells.
      Minodronate decreased DNA synthesis and increased apoptotic cell death of
      cultured melanoma cells as well. Our present study suggests that minodronate
      might suppress melanoma growth and improve survival in nude mice by two
      independent mechanisms; one is by blocking the VEGF signaling in endothelial
      cells, and the other is by inducing apoptotic cell death of melanoma. The present
      study provides a novel potential therapeutic strategy for the treatment of
      melanoma.

PMID- 15579432
TI  - Transgenic mice expressing a ligand-inducible cre recombinase in osteoblasts and
      odontoblasts: a new tool to examine physiology and disease of postnatal bone and
      tooth.
AB  - The skeleton supports body structures in vertebrates and helps maintain calcium
      homeostasis throughout life. Disruption of genes involved in mammalian bone
      formation has often led to embryonic lethality, hence preventing study of these
      genes' role in adult animals. To develop a usable tool for such study, we
      generated transgenic mice in which a 2.3-kb mouse Col1a1 proximal promoter, which
      is active in all osteoblasts, drives a transgene coding for a polypeptide
      consisting of Cre recombinase fused to a mutated ligand-binding domain of the
      estrogen receptor. In this Col1a1-CreERT2 mouse line, expression patterns of the
      transgene and of the resulting Cre-mediated DNA recombination are analyzed by
      crossing with ROSA26 reporter mice and by measurement of beta-galactosidase
      activity and X-gal staining. Exposure to 4-hydroxytamoxifen induced Cre-mediated
      recombination in osteoblasts in virtually all bones and in odontoblasts in teeth
      of both embryos and postnatal mice. The generation of these transgenic mice
      provides a new and important tool with which to study the function of specific
      genes in bone and tooth physiology and diseases in intact animals after birth.

PMID- 15579433
TI  - Interferon-gamma protects against chronic viral myocarditis by reducing mast cell
      degranulation, fibrosis, and the profibrotic cytokines transforming growth factor
      beta 1, interleukin-1 beta, and interleukin-4 in the heart.
AB  - Inflammatory fibrosis is a characteristic feature of myocarditis, dilated
      cardiomyopathy (DCM), and congestive heart failure. Th1-type immune responses,
      mediated by interleukin (IL)-12-induced interferon (IFN)-gamma, are believed to
      exacerbate autoimmune diseases including myocarditis. In this study, we examined
      the effect of IL-12R beta 1 and IFN-gamma deficiency on the development of
      chronic CB3-induced myocarditis using knockout mice. We found increased chronic
      CB3-induced myocarditis (14.1 to 43.1%, P < 0.001); pericarditis (1.5 to 7.6%, P
      < 0.001); fibrosis (9.7 to 27.4%, P < 0.05); and the profibrotic cytokines
      transforming growth factor-beta(1), IL-1 beta, and IL-4 in the hearts of IFN
      gamma-deficient mice. All mice infected with CB3 developed DCM, but IFN-gamma
      deficient mice developed a fibrous, adhesive pericarditis associated with
      increased numbers of degranulating mast cells (MCs) in the pericardium (26.6 to
      45.9%, P < 0.01), increased histamine levels (716 to 1930 ng/g of heart, P <
      0.01), and reduced survival (100 to 43%). In contrast, IL-12R beta 1 deficiency
      did not significantly alter the development of chronic myocarditis. Thus, IFN
      gamma protects against the development of severe chronic myocarditis,
      pericarditis, and DCM after CB3 infection by reducing MC degranulation, fibrosis,
      and the profibrotic cytokines transforming growth factor-beta(1), IL-1 beta, and
      IL-4 in the heart.

PMID- 15579434
TI  - Dysmorphogenesis of kidney cortical peritubular capillaries in angiopoietin-2
      deficient mice.
AB  - Angiopoietin-2 (Ang-2) modulates Tie-2 receptor activation. In mouse kidney
      maturation, Ang-2 is expressed in arteries, with lower levels in tubules, whereas
      Tie-2 is expressed by endothelia. We hypothesized that Ang-2 deficiency disrupts
      kidney vessel patterning. The normal renal cortical peritubular space contains
      fenestrated capillaries, which have few pericytes; they receive water and solutes
      which proximal tubules reclaim from the glomerular filtrate. In wild-type
      neonates, alpha smooth muscle actin (alpha SMA), platelet-derived growth factor
      receptor beta (PDGFR beta), and desmin-expressing cells were not prominent in
      this compartment. In Ang-2 null mutants, alpha SMA, desmin, and PDGFR beta
      prominently immunolocalized in cortical peritubular locations. Some alpha SMA
      positive cells were closely associated with CD31- and Tie-2-positive peritubular
      capillary endothelia, and some of the alpha SMA-positive cells expressed PDGFR
      beta, desmin, and neural/glial cell 2 (NG2), consistent with a pericyte-like
      identity. Immunoblotting suggested an increase of total and tyrosine
      phosphorylated Tie-2 proteins in null mutant versus wild-type kidneys, and
      electron microscopy confirmed disorganized capillaries and adjacent cells in
      cortical peritubular spaces in mutant neonate kidneys. Hence, Ang-2 deficiency
      causes dysmorphogenesis of cortical peritubular capillaries, with adjacent cells
      expressing pericyte-like markers; we speculate the latter effect is caused by
      disturbed paracrine signaling between endothelial and surrounding mesenchymal
      precursor cells.

PMID- 15579435
TI  - Regulation and function of trefoil factor family 3 expression in the biliary
      tree.
AB  - Microarray analysis identified trefoil factor family 3 (TFF3) as a gene expressed
      in biliary epithelial cells (BECs), regulated by interleukin (IL)-6, and
      potentially involved in biliary pathophysiology. We therefore studied the
      regulation and function of BEC TFF3, in vitro and in vivo in IL-6(+/+) and IL-6(
      /-) mice subjected to chronic bile duct ligation for 12 weeks. In vitro studies
      showed that IL-6 wild-type (IL-6(+/+)) BECs expressed higher TFF3 mRNA and
      protein levels than IL-6-deficient (IL-6(-/-)) BECs. BEC TFF3 expression is
      dependent primarily on signal transducer and activator of transcription (STAT3)
      signaling, but the reciprocal negative regulation known to exist between the
      intracellular IL-6/gp130 signaling pathways, STAT3 and mitogen-activated protein
      kinase (MAPK), importantly contributes to BEC TFF3 expression. Specifically
      blocking STAT3 activity with a dominant-negative molecule or treatment with a
      growth factor such as hepatocyte growth factor, which increases MAPK signaling,
      decreases BEC TFF3 expression. In contrast, specifically blocking MAPK activity
      with PD98059 significantly increased BEC TFF3 expression. Higher BEC TFF3 levels
      in IL-6(+/+) BECs were associated with significantly better migration than IL-6(
      /-) BECs in a wound-healing assay and defective IL-6(-/-) BEC migration was
      reversed with exogenous TFF3. In vivo, hepatic TFF3 mRNA and protein expression
      was limited to BECs and dependent significantly on STAT3 signaling, but was
      influenced by other factors present after bile duct ligation. Comparable results
      were obtained in normal and diseased human tissue samples. In conclusion the
      regulation and function of BEC TFF3 expression is similar to the colon. BEC TFF3
      expression depends primarily on gp130/STAT3 and contributes to BEC migration and
      wound healing. Therefore, use of recombinant IL-6 or TFF3 peptides should exert a
      therapeutic role in preventing biliary strictures in liver allografts.

PMID- 15579436
TI  - Role of metalloelastase in a model of allergic lung responses induced by
      cockroach allergen.
AB  - Our laboratory and others have shown an important role of metalloelastase (MMP
      12) in the pathogenesis of acute and chronic lung injury. Because chronic asthma
      is characterized by airway inflammation and alterations in the airway
      extracellular matrix, we explored the role of metalloelastase in a model of
      allergic airway inflammation induced by cockroach antigen (CRA). Using MMP-12
      deficient mice we found a significant reduction in CRA-induced inflammatory
      injury, as evidenced by fewer peribronchial leukocytes, significantly less
      protein in the bronchoalveolar lavage (BAL) fluid, and a significant reduction in
      the number of infiltrating neutrophils, eosinophils, and macrophages, relative to
      wild-type mice. Although we did not find a significant reduction in the number of
      T cells in the injured MMP-12-deficient animals as compared to controls, levels
      of the chemotactic factors interleukin-5, macrophage inflammatory protein-1
      alpha, monocyte chemoattractant protein-1, thymus activation regulated chemokine,
      and the proinflammatory cytokine tumor necrosis factor-alpha were significantly
      reduced in the bronchoalveolar lavage fluid of CRA-challenged MMP-12-deficient
      mice, relative to CRA-challenged control animals. These studies indicate that MMP
      12 plays an important proinflammatory role in the development of allergic
      inflammation in the CRA model. Alterations in the levels of chemotactic factors
      and other proinflammatory cytokines in the MMP-12-deficient mice may underlie the
      decrease in leukocyte recruitment into inflamed lungs.

PMID- 15579437
TI  - Alterations in galectin-3 expression and distribution correlate with breast
      cancer progression: functional analysis of galectin-3 in breast epithelial
      endothelial interactions.
AB  - To define the role of galectin-3 in breast cancer progression, we have used a
      novel three-dimensional co-culture system that recapitulates in vivo reciprocal
      functional breast epithelial-endothelial cell-cell and cell-matrix interactions,
      and examined the expression of galectin-3 mRNA and protein in human breast tumors
      and xenografts. Galectin-3 is required for the stabilization of epithelial
      endothelial interaction networks because immunoneutralization with galectin-3
      antibodies abolishes the interactions in a dose-dependent manner. Co-culture of
      epithelial cells with endothelial cells results in increase in levels of secreted
      galectin-3 and presence of proteolytically processed form of galectin-3 in the
      conditioned media. In contrast, intracellular galectin-3 predominantly exists in
      the intact form. This difference in sensitivity to proteolytic processing of
      secreted versus intracellular galectin-3 probably arises from differences in
      accessibility of protease-sensitive sites, levels, and/or type of activated
      protease(s), and may be indicative of different functional roles for intact and
      processed galectin-3. To determine whether the proteolytically cleaved galectin-3
      retains its ability to bind to endothelial cells, binding assays were performed
      with the full-length and matrix metallopeoteinase-2-cleaved recombinant galectin
      3. Although a dose-dependent increase in binding to human umbilical vein
      endothelial cells was observed with both full-length and cleaved galectin-3,
      proteolytically cleaved galectin-3 displayed approximately 20-fold higher
      affinity for human umbilical vein endothelial cells as compared to the full
      length protein. Examination of galectin-3 expression in breast tumors and
      xenografts revealed elevated levels of galectin-3 mRNA and protein in the luminal
      epithelial cells of normal and benign ducts, down-regulation in early grades of
      ductal carcinoma in situ (DCIS), and re-expression in peripheral tumor cells as
      DCIS lesions progressed to comedo-DCIS and invasive carcinomas. These data
      suggest that galectin-3 expression is associated with specific morphological
      precursor subtypes of breast cancer and undergoes a transitional shift in
      expression from luminal to peripheral cells as tumors progressed to comedo-DCIS
      or invasive carcinomas. Such a localized expression of galectin-3 in cancer cells
      proximal to the stroma could lead to increased invasive potential by inducing
      novel or better interactions with the stromal counterparts.

PMID- 15579438
TI  - CTNNB1 mutations and overexpression of Wnt/beta-catenin target genes in WT1
      mutant Wilms' tumors.
AB  - Gain-of-function mutations in exon 3 of beta-catenin (CTNNB1) are specific for
      Wilms' tumors that have lost WT1, but 50% of WT1-mutant cases lack such "hot
      spot" mutations. To ask whether stabilization of beta-catenin might be essential
      after WT1 loss, and to identify downstream target genes, we compared expression
      profiles in WT1-mutant versus WT1 wild-type Wilms' tumors. Supervised and
      nonsupervised hierarchical clustering of the expression data separated these two
      classes of Wilms' tumor. The WT1-mutant tumors overexpressed genes encoding
      myogenic and other transcription factors (MOX2, LBX1, SIM2), signaling molecules
      (TGFB2, FST, BMP2A), extracellular Wnt inhibitors (WIF1, SFRP4), and known beta
      catenin/TCF targets (FST, CSPG2, CMYC). Beta-Catenin/TCF target genes were
      overexpressed in the WT1-mutant tumors even in the absence of CTNNB1 exon 3
      mutations, and complete sequencing revealed gain-of-function mutations elsewhere
      in the CTNNB1 gene in some of these tumors, increasing the overall mutation
      frequency to 75%. Lastly, we identified and validated a novel direct beta-catenin
      target gene, GAD1, among the WT1-mutant signature genes. These data highlight two
      molecular classes of Wilms' tumor, and indicate strong selection for
      stabilization of beta-catenin in the WT1-mutant class. Beta-Catenin stabilization
      can initiate tumorigenesis in other systems, and this mechanism is likely
      critical in tumor formation after loss of WT1.

PMID- 15579439
TI  - Integrity of cell-cell contacts is a critical regulator of TGF-beta 1-induced
      epithelial-to-myofibroblast transition: role for beta-catenin.
AB  - Injury of the tubular epithelium and TGF-beta1-induced conversion of epithelial
      cells to alpha-smooth muscle actin (SMA)-expressing myofibroblasts are key
      features of kidney fibrosis. Since injury damages intercellular junctions and
      promotes fibrosis, we hypothesized that cell contacts are critical regulators of
      TGF-beta 1-triggered epithelial-to-mesenchymal transition (EMT). Here we show
      that TGF-beta 1 was unable to induce EMT in intact confluent monolayers, but
      three different models of injury-induced loss of epithelial integrity
      (subconfluence, wounding, and contact disassembly by Ca(2+)-removal) restored its
      EMT-inducing effect. This manifested in loss of E-cadherin, increased fibronectin
      production and SMA expression. TGF-beta 1 or contact disassembly alone only
      modestly stimulated the SMA promoter in confluent layers, but together exhibited
      strong synergy. Since beta-catenin is a component of intact adherens junctions,
      but when liberated from destabilized contacts may act as a transcriptional co
      activator, we investigated its role in TGF-beta 1-provoked EMT. Contact
      disassembly alone induced degradation of E-cadherin and beta-catenin, but TGF
      beta1 selectively rescued beta-catenin and stimulated the beta-catenin-driven
      reporter TopFLASH. Moreover, chelation of free beta-catenin with the N-cadherin
      cytoplasmic tail suppressed the TGF-beta1 plus contact disassembly-induced SMA
      promoter activation and protein expression. These results suggest a beta-catenin
      dependent two-hit mechanism in which both an initial epithelial injury and TGF
      beta 1 are required for EMT.

PMID- 15579440
TI  - Expression of stromal cell-derived factor-1 and of its receptor CXCR4 in liver
      regeneration from oval cells in rat.
AB  - Stromal cell-derived factor-1 is a chemokine that plays a major role during
      embryogenesis. Since stromal cell-derived factor-1 and its unique receptor CXCR4
      are involved in the differentiation of progenitor cells, we studied the
      expression of this chemokine and of its receptor in hepatic regeneration from
      precursor oval cells. Hepatic regeneration was induced by treating rats with 2
      acetylaminofluorene, and followed by partial hepatectomy. Oval cell accumulation,
      which predominated in periportal regions, reached a maximum at days 9 to 14 after
      hepatectomy and declined thereafter. Oval cells strongly expressed stromal cell
      derived factor-1 protein and mRNA. CXCR4 mRNA hepatic level paralleled the number
      of oval cells and in situ hybridization showed CXCR4 mRNA expression by these
      cells. Treatment of rats with fucoidan, a sulfated polysaccharide which binds to
      stromal cell-derived factor-1 and blocks its biological effects, markedly
      decreased oval cell accumulation in five of the seven treated rats. In
      conclusion, our data demonstrate an expression of stromal cell-derived factor-1
      and of its receptor CXCR4 in oval cells during hepatic regeneration and strongly
      suggest that stromal cell-derived factor-1 stimulates the proliferation of these
      precursor cells through an autocrine/paracrine pathway.

PMID- 15579441
TI  - Hypoxia in renal disease with proteinuria and/or glomerular hypertension.
AB  - Despite the increasing need to identify and quantify tissue oxygenation at the
      cellular level, relatively few methods have been available. In this study, we
      developed a new hypoxia-responsive reporter vector using a hypoxia-responsive
      element of the 5' vascular endothelial growth factor untranslated region and
      generated a novel hypoxia-sensing transgenic rat. We then applied this animal
      model to the detection of tubulointerstitial hypoxia in the diseased kidney. With
      this model, we were able to identify diffuse cortical hypoxia in the puromycin
      aminonucleoside-induced nephrotic syndrome and focal and segmental hypoxia in the
      remnant kidney model. Expression of the hypoxia-responsive transgene increased
      throughout the observation period, reaching 2.2-fold at 2 weeks in the puromycin
      aminonucleoside model and 2.6-fold at 4 weeks in the remnant kidney model,
      whereas that of vascular endothelial growth factor showed a mild decrease,
      reflecting distinct behaviors of the two genes. The degree of hypoxia showed a
      positive correlation with microscopic tubulointerstitial injury in both models.
      Finally, we identified the localization of proliferating cell nuclear antigen
      positive, ED-1-positive, and terminal dUTP nick-end labeled-positive cells in the
      hypoxic cortical area in the remnant kidney model. We propose here a possible
      pathological tie between chronic tubulointerstitial hypoxia and progressive
      glomerular diseases.

PMID- 15579442
TI  - Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat
      liver allograft rejection.
AB  - Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion
      to endothelia at sites of inflammation, but its functional role in vivo has not
      been tested in any rodent model. Here we report the effects of VAP-1 blockade on
      rat liver allograft rejection. BN recipients of PVG liver allografts (known to
      develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new
      anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every
      other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On
      day 7, samples were collected for transplant aspiration cytology, histology, and
      immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected
      by VAP-blockade. The total inflammation, mainly the number of active lymphoid
      cells, in transplant aspiration cytology was significantly decreased in animals
      treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units,
      respectively) compared to control (6.6 +/- 1.0) (P < 0.05). In histology, the
      intensity of portal inflammation was significantly decreased (P < 0.05). The
      amount of T cells expressing activation markers diminished. This is the first
      demonstration in any prolonged in vivo model that VAP-1 plays an important role
      in lymphocyte infiltration to sites of inflammation, and, in particular, liver
      allograft rejection.

PMID- 15579443
TI  - Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute
      pancreatitis.
AB  - In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-gamma
      (PI3K gamma) regulates several key pathological responses to cholecystokinin
      hyperstimulation in vitro. Thus, using mice lacking PI3K gamma, we studied the
      function of this enzyme in vivo in two different models of acute pancreatitis.
      The disease was induced by supramaximal concentrations of cerulein and by feeding
      mice a choline-deficient/ethionine-supplemented diet. Although the secretive
      function of isolated pancreatic acini was identical in mutant and control
      samples, in both models, genetic ablation of PI3K gamma significantly reduced the
      extent of acinar cell injury/necrosis. In agreement with a protective role of
      apoptosis in pancreatitis, PI3K gamma-deficient pancreata showed an increased
      number of apoptotic acinar cells, as determined by terminal dUTP nick-end
      labeling and caspase-3 activity. In addition, neutrophil infiltration within the
      pancreatic tissue was also reduced, suggesting a dual action of PI3K gamma, both
      in the triggering events within acinar cells and in the subsequent neutrophil
      recruitment and activation. Finally, the lethality of the choline
      deficient/ethionine-supplemented diet-induced pancreatitis was significantly
      reduced in mice lacking PI3K gamma. Our results thus suggest that inhibition of
      PI3K gamma may be of therapeutic value in acute pancreatitis.

PMID- 15579444
TI  - Deleting TCR alpha beta+ or CD4+ T lymphocytes leads to opposite effects on site
      specific atherosclerosis in female apolipoprotein E-deficient mice.
AB  - Recent studies have demonstrated the importance of lymphocytes, especially CD4(+)
      T cells, in early lesions of atherosclerosis in hypercholesterolemic mice.
      However, the role of other T cell subpopulations, like CD8(+) T cells or TCR
      gamma delta T lymphocytes, is not yet clear. We have therefore generated
      apolipoprotein E-deficient mice genetically deficient in specific T lymphocyte
      subpopulations and measured atherosclerotic lesions in the aortic sinus and en
      face whole aorta preparation at 18 weeks and at 1 year of age. Whereas TCR gamma
      delta(+) T lymphocytes appeared to play a modest role, TCR alpha beta(+) T
      lymphocytes played a major role as their deficiency significantly prevented early
      and late atherosclerosis at all arterial sites. However, neither CD4(+) nor
      CD8(+) T cells induced any significant decrease of the lesions at the aortic
      sinus, suggesting that compensatory proatherogenic mechanisms are operating at
      this site. Interestingly, the absence of CD4(+) T cells led to a dramatic
      increase in early lesion abundance at the level of the descending thoracic and
      abdominal aorta, which was still obvious at 1 year. In conclusion, whereas the
      TCR alpha beta(+) lymphocyte subset in its whole contribute to aggravate both
      early and late atherosclerosis, the CD4(+) T subpopulation appears to be
      critically protective at the level of the lower part of the aorta.

PMID- 15579445
TI  - E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by
      microarray analysis.
AB  - Estrogen has been postulated to be involved in inhibition of vascular smooth
      muscle cell (VSMC) proliferation mainly via estrogen receptor (ER), but the
      detailed mechanism has remained primarily unknown. Therefore, in this study,
      microarray analysis was used in two types of cultured human VSMCs: one positive
      for ER alpha, and the other for ER beta, which were treated by estrogens to
      detect the estrogen-responsive genes. We also used quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) to evaluate mRNA levels of
      selective target gene (TG) in these cells. We further studied whether the TG
      product was involved in inhibition of proliferation using small interfering RNA
      (siRNA) of the TG transfection. We subsequently used quantitative RT-PCR and in
      situ hybridization analysis to evaluate the expression of these gene products in
      human aorta. E4F1, a possible inducer of cell growth arrest, was markedly
      increased only in ER alpha-positive VSMCs by estrogens in both microarray and RT
      PCR analyses. Blocking of E4F1 using siRNA suppressed estrogenic inhibition of ER
      alpha-positive VSMC proliferation. E4F1 mRNA was abundant in premenopausal female
      aorta with mild atherosclerotic changes. E4F1 is therefore considered one of the
      estrogen-responsive genes involving ER alpha-mediated inhibition of VSMC
      proliferation and may play an important role in estrogen-related atheroprotection
      of human aorta.

PMID- 15579446
TI  - Advanced glycation end-products induce connective tissue growth factor-mediated
      renal fibrosis predominantly through transforming growth factor beta-independent
      pathway.
AB  - Advanced glycation end-products (AGEs) play a critical role in diabetic
      nephropathy by stimulating extracellular matrix (ECM) synthesis. Connective
      tissue growth factor (CTGF) is a potent inducer of ECM synthesis and increases in
      the diabetic kidneys. To determine the critical role of CTGF in AGE-induced ECM
      accumulation leading to diabetic nephropathy, rats were given AGEs by intravenous
      injection for 6 weeks. AGE treatment induced a significant renal ECM
      accumulation, as shown by increases in periodic acid-Schiff-positive materials,
      fibronectin, and type IV collagen (Col IV) accumulation in glomeruli, and a mild
      renal dysfunction, as shown by increases in urinary volume and protein content.
      AGE treatment also caused significant increases in renal CTGF and transforming
      growth factor (TGF)-beta 1 mRNA and protein expression. Direct exposure of rat
      mesangial cells to AGEs in vitro significantly induced increases in fibronectin
      and Col IV production, which could be completely prevented by pretreatment with
      anti-CTGF antibody. AGE treatment also significantly increased both TGF-beta 1
      and CTGF mRNA expression; however, inhibition of TGF-beta 1 mRNA expression by
      shRNA or neutralization of TGF-beta 1 protein by anti-TGF-beta 1 antibody did not
      significantly prevent AGE-increased expression of CTGF mRNA and protein. These
      results suggest that AGE-induced CTGF expression, predominantly through a TGF
      beta 1-independent pathway, plays a critical role in renal ECM accumulation
      leading to diabetic nephropathy.

PMID- 15579447
TI  - Critical role for galectin-3 in airway inflammation and bronchial
      hyperresponsiveness in a murine model of asthma.
AB  - Galectin-3 is a member of a beta-galactoside-binding animal lectin family.
      Previous in vitro studies have demonstrated that galectin-3 is involved in a
      number of activities; however, the roles of this lectin in physiological and
      pathological processes in vivo remain to be elucidated. Herein, we show, in a
      murine model of ovalbumin (OVA)-induced asthma that 1) peribronchial inflammatory
      cells expressed large amounts of galectin-3; 2) bronchoalveolar lavage fluid from
      OVA-challenged mice contained significantly higher levels of galectin-3 compared
      to control mice; and 3) macrophages in bronchoalveolar lavage fluid were the
      major cell type that contained galectin-3. We investigated the role of galectin-3
      in the allergic airway response by comparing galectin-3-deficient (gal3(-/-))
      mice and wild-type (gal3(+/+)) mice. OVA-sensitized gal3(-/-) mice developed
      fewer eosinophils and lower goblet cell metaplasia, after airway OVA challenge
      compared to similarly treated gal3(+/+) mice. In addition, the OVA-sensitized
      gal3(-/-) mice developed significantly less airway hyperresponsiveness after
      airway OVA challenge compared to gal3(+/+) mice. Finally, gal3(-/-) mice
      developed a lower Th2 response, but a higher Th1 response, suggesting that
      galectin-3 regulates the Th1/Th2 response. We conclude that galectin-3 may play
      an important role in the pathogenesis of asthma and inhibitors of this lectin may
      prove useful for treatment of this disease.

PMID- 15579448
TI  - Differences in scrapie-induced pathology of the retina and brain in transgenic
      mice that express hamster prion protein in neurons, astrocytes, or multiple cell
      types.
AB  - Prion protein (PrP) is expressed in many tissues and is required for
      susceptibility to scrapie and other prion diseases. To investigate the role of
      PrP expression in different cell types on pathology in retina and brain after
      scrapie infection, we examined transgenic mice expressing hamster PrP from the
      PrP promoter (tg7), the neuron-specific enolase promoter (tgNSE), or the
      astrocyte-specific glial fibrillary acidic protein promoter (tgGFAP). After
      intraocular inoculation with hamster scrapie, clinical disease developed in tg7
      and tgNSE mice by 100 days and in tgGFAP mice by 350 days. Astrogliosis and
      scrapie-associated protease-resistant PrP (PrP-res) were detected in retina and
      brain before clinical onset. Retinal PrP-res was present in high amounts in both
      tg7 and tgNSE mice, however only tg7 mice developed retinal degeneration and
      extensive apoptosis. In contrast, in all three lines of mice high levels of brain
      PrP-res accompanied by neurodegeneration were observed. Thus, PrP expression on
      neurons or astrocytes was sufficient for development of scrapie-induced
      degeneration in brain but not in retina. The combined effects of PrP-res
      production in multiple cell types was required to produce retinal degeneration,
      whereas in brain PrP-res production by neurons or astrocytes alone was sufficient
      to cause neuronal damage via direct or indirect mechanisms.

PMID- 15579449
TI  - T lymphocytes do not directly mediate the protective effect of estrogen on
      experimental autoimmune encephalomyelitis.
AB  - Gender influences mediated by 17 beta-estradiol (E2) have been associated with
      susceptibility to and severity of autoimmune diseases such as diabetes,
      arthritis, and multiple sclerosis. In this regard, we have shown that estrogen
      receptor-alpha (Esr1) is crucial for the protective effect of 17 beta-estradiol
      (E2) in murine experimental autoimmune encephalitis (EAE), an animal model of
      multiple sclerosis. The expression of estrogen receptors among various immune
      cells (eg, T and B lymphocytes, antigen-presenting cells) suggests that the
      therapeutic effect of E2 is likely mediated directly through specific receptor
      binding. However, the target immune cell populations responsive to E2 treatment
      have not been identified. In the current study, we induced EAE in T-cell
      deficient, severe combined immunodeficient mice or in immunocompetent mice with
      encephalitogenic T cells from wild-type Esr1+/+ or Esr1 knockout (Esr1-/-) donors
      and compared the protective E2 responses. The results showed that E2-responsive,
      Esr1+/+ disease-inducing encephalitogenic T cells were neither necessary nor
      sufficient for E2-mediated protection from EAE. Instead, the therapeutic response
      appeared to be mediated through direct effects on nonlymphocytic, E2-responsive
      cells and down-regulation of the inflammatory response in the central nervous
      system. These results provide the first demonstration that the protective effect
      of E2 on EAE is not mediated directly through E2-responsive T cells and raise the
      alternative possibility that nonlymphocytic cells such as macrophages, dendritic
      cells, or other nonlymphocytic cells are primarily responsive to E2 treatment in
      EAE.

PMID- 15579450
TI  - Chimerism of metanephric adenoma but not of carcinoma in kidney transplants.
AB  - Recipient-derived cells integrate into renal allografts inducing organ-specific
      microchimerism. Circulating pluripotent progenitor cells with high plasticity for
      differentiation were suggested as a potential source of allograft chimerism.
      Whether or not these cells also contribute to tumor formation in renal
      transplants is unknown. We analyzed six histologically different tumors in renal
      allografts for the presence of recipient-derived cells. To circumvent dependency
      on gender mismatch, a polymerase chain reaction assay for highly polymorphic
      short tandem repeat marker (DNA fingerprinting) in combination with laser
      microdissection was applied. Pure tumor cell populations were harvested by laser
      microdissection after immunohistochemical (CD45/CD68) marking of contaminating
      leukocytes. In cases of gender mismatch (n = 2), results were confirmed by sex
      chromosome in situ hybridization. Two metanephric adenomas demonstrated
      microchimerism comprising both donor- and recipient-derived tumor cells. Two
      clear cell carcinomas, one transitional cell carcinoma, and one renal cortical
      adenoma were all of donor origin without chimerism. We conclude that except for
      metanephric adenomas, tumors arising in renal transplants originate completely
      from graft cells. The mixed derivation of metanephric adenomas indicates an
      incorporation of recipient-derived progenitor cells. This finding suggests that
      adult stem cells can assume neoplastic phenotypes.

PMID- 15579451
TI  - Thrombospondin 2 functions as an endogenous regulator of angiogenesis and
      inflammation in rheumatoid arthritis.
AB  - Thrombospondin 2 (TSP2), a matricellular protein with a primary role in
      modulating cell-matrix interactions, has been implicated in tissue repair and
      foreign body responses. Here we show that TSP2 has regulatory function in the
      chronic inflammatory lesions of rheumatoid arthritis. Tissue TSP2, produced by
      synovial fibroblasts, endothelial cells, and macrophages correlated not only with
      the intensity of angiogenesis but also with the architecture of lymphoid
      infiltrates. Synovial tissues with diffuse inflammatory infiltrates had high
      levels of TSP2, whereas synovial tissues with ectopic germinal center reactions
      and T cell-B cell aggregates produced low levels. Cell-based gene therapy with
      TSP2 was used to examine the in vivo effects of the matrix protein on
      neoangiogenesis and lymphoid organization. Human synovium-severe combined
      immunodeficiency (SCID) mouse chimeras were treated with TSP2-transfected
      fibroblasts deposited into the peritoneum. Overexpression of TSP2 led to the
      accumulation of TSP2 protein in the inflamed synovium and resulted in a prompt
      inhibition of lesional vascularization. Beside its anti-angiogenic activity, TSP2
      also suppressed the production of the proinflammatory mediators, interferon-gamma
      and tumor necrosis factor-alpha, and induced the depletion of tissue-residing T
      cells. We propose that TSP2 is an endogenous regulator of angiogenesis and
      autoimmune inflammation in the synovium and represents a protective mechanism
      preventing ectopic lympho-organogenesis and persistent inflammation in this
      tissue site.

PMID- 15579452
TI  - Biphasic expression of two paracrine melanogenic cytokines, stem cell factor and
      endothelin-1, in ultraviolet B-induced human melanogenesis.
AB  - Stem cell factor (SCF) and endothelin-1 (ET-1) have been reported to be up
      regulated at the protein and gene levels in human epidermis after ultraviolet B
      (UVB) irradiation and to play central roles in UVB-induced pigmentation. However,
      little is known about the time sequence of SCF and ET-1 expression in UVB-exposed
      human epidermis and the coordination of their roles during epidermal
      pigmentation. To clarify such parameters in UVB-exposed human skin, we measured
      the expression patterns of SCF and ET-1 (as well as of their corresponding
      receptors) at the gene level at various times during UVB-induced human
      pigmentation. When human forearm skin was exposed to UVB radiation at two minimal
      erythemal doses, the expression of SCF mRNA transcripts was significantly
      enhanced at 3 days after irradiation with an early decrease and subsequently
      constant expression of SCF receptor (c-KIT) mRNA transcripts. In contrast, up
      regulation of ET-1 and endothelin B receptor (ET(B)R) mRNA expression was
      synchronized at 5 to 10 days after irradiation in concert with an increased
      expression of tyrosinase mRNA transcripts and the increase in pigmentation. In
      parallel the expression of tyrosinase and ET(B)R proteins as well as ET-1 was up
      regulated at 7 to 10 days after irradiation, whereas KIT protein decreased at 3
      days after irradiation and returned to the nonirradiated control level at 5 days
      after irradiation. When cultured human melanocytes were treated with human
      recombinant SCF, ET(B)R protein expression and the binding of (125)I-labeled ET-1
      to the ET(B)R were significantly increased, further suggesting the preferential
      and coordinated role of early expression of SCF in UVB-induced melanogenesis.
      These findings suggest that SCF/KIT signaling is predominantly involved in the
      early phase of UVB-induced human pigmentation during which it stimulates the ET
      1/ET(B)R linkage that is associated with the later phase of UVB-induced
      melanogenesis.

PMID- 15579453
TI  - Cell tropism of simian immunodeficiency virus in culture is not predictive of in
      vivo tropism or pathogenesis.
AB  - SIVmac239/316 is a molecular clone derived from SIVmac239 that differs from the
      parental virus by nine amino acids in env. This virus, unlike the parental
      SIVmac239, is able to replicate well in alveolar macrophages in culture. We have
      not however, observed macrophage-associated inflammatory disease in any animal
      infected with SIVmac239/316. Therefore, we sought to examine the cell tropism of
      this virus in vivo in multiple tissues using in situ hybridization combined with
      immunohistochemistry and multilabel confocal microscopy for viral nucleic acid
      and multiple cell-type-specific markers for macrophages and T lymphocytes.
      Tissues examined included brain, heart, lung, lymph nodes, spleen, thymus, and
      small and large intestine. Matched tissues from macaques infected with the
      parental SIVmac239 and uninfected macaques were also examined. Many infected
      cells were detected in the tissues of animals infected with SIVmac239 and
      SIVmac239/316 although there appeared to be fewer positive cells in animals
      infected with SIVmac239/316. Surprisingly, in light of the cell culture
      observations, nearly every simian immunodeficiency virus-infected cell in animals
      inoculated with SIVmac239/316 was a T lymphocyte rather than a macrophage. This
      was true both during early infection (first 2 months) and in terminal disease. In
      contrast, as previously described, SIVmac239 was found in both T cells and
      macrophages in tissues as early as 21 days after infection. These studies
      indicate that during both acute and chronic SIVmac239/316 infection T lymphocytes
      rather than macrophages are the principal targets in vivo. These data combined
      with the absence of macrophage-associated lesions in SIVmac239/316-infected
      animals indicate that in vitro cell tropism is not predictive of in vivo tropism
      or disease pathogenesis.

PMID- 15579454
TI  - Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of
      Leishmania donovani infection.
AB  - Tumor necrosis factor (TNF) is critical for the control of visceral leishmaniasis
      caused by Leishmania donovani. However, the role of the related cytokine
      lymphotoxin (LT) alpha in this infection is unknown. Here we report that C57BL/6
      mice deficient in TNF (B6.TNF(-/-)) or LT alpha (B6.LT alpha(-/-)) have increased
      susceptibility to hepatic L. donovani infection. Furthermore, the outcome of
      infection in bone marrow chimeric mice is dependent on donor hematopoietic cells,
      indicating that developmental defects in lymphoid organs were not responsible for
      increased susceptibility to L. donovani. Although both LT alpha and TNF regulated
      the migration of leukocytes into the sinusoidal area of the infected liver, their
      roles were distinct. LT alpha was essential for migration of leukocytes from
      periportal areas, an event consistent with LT alpha-dependent up-regulation of
      VCAM-1 on liver sinusoid lining cells, whereas TNF was essential for leukocyte
      recruitment to the liver. During visceral leishmaniasis, both cytokines were
      produced by radio-resistant cells and by CD4(+) T cells. LT alpha and TNF
      production by the former was required for granuloma assembly, while production of
      these cytokines by CD4(+) T cells was necessary to control parasite growth. The
      production of inducible nitric oxide synthase was also found to be deficient in
      TNF- and LT alpha-deficient infected mice. These results demonstrate that both LT
      alpha and TNF are required for control of L. donovani infection in
      noncompensatory ways.

PMID- 15579455
TI  - Expression of cholecystokinin-2/gastrin receptor in the murine pancreas modulates
      cell adhesion and cell differentiation in vivo.
AB  - The presence of gastrin and cholecystokinin-2 (CCK2) receptors in human
      preneoplastic and neoplastic gastrointestinal lesions suggests a role in cancer
      development. In addition to the growth-promoting action of gastrin, recently a
      role of the cholecystokinin-2/gastrin receptor (CCK2-R) modulating cellular
      morphology in cultured epithelial cells has been shown. Here, we have
      investigated in transgenic (ElasCCK2) mice whether ectopic expression of human
      CCK2-R in the exocrine pancreas affected epithelial differentiation. Cellular
      localization of cell adhesion molecules, differentiation markers, and
      transcription factors was determined using immunofluorescence techniques. Before
      tumor formation, expression and subcellular localization of proteins of the
      adherens junction complex, differentiation markers, and transcription factors
      were altered in ElasCCK2 exocrine pancreas, indicating an evolution from an
      acinar to a ductal phenotype. Loss of cell polarity, defective secretion, and
      loss of intercellular adhesion in acini of ElasCCK2 mice was confirmed by
      ultrastructural analysis. Finally, expression of the transgene in mice treated
      with the carcinogen azaserine resulted in enhanced size of preneoplastic lesions
      as well as an increased degree of acinar-ductal transdifferentiation. Thus, these
      data represent the first evidence for the CCK2-R modulating intercellular
      adhesion and cell fate in vivo and show that these alterations may contribute to
      enhanced sensitivity of ElasCCK2 pancreas to chemical carcinogens.

PMID- 15579456
TI  - Role of Cks1 overexpression in oral squamous cell carcinomas: cooperation with
      Skp2 in promoting p27 degradation.
AB  - Down-regulation of p27 is frequently observed in various cancers due to an
      enhancement of its degradation. Skp2 is required for the ubiquitination and
      consequent degradation of p27 protein. Another protein called Cks1 is also
      required for p27 ubiquitination in the SCF(Skp2) ubiquitinating machinery. In the
      present study, we examined Cks1 expression and its correlation with p27 in oral
      squamous cell carcinoma (OSCC) derived from tongue and gingiva. By
      immunohistochemical analysis, high expression of Cks1 was present in 62% of OSCCs
      in comparison with 0% of normal mucosae. In addition, 65% of samples with low p27
      expression displayed high Cks1 levels. Finally, Cks1 expression was well
      correlated with Skp2 expression and poor prognosis. To study the role of Cks1
      overexpression in p27 down-regulation, we transfected Cks1 with or without Skp2
      into OSCC cells. Cks1 transfection could not induce a p27 down-regulation by
      itself, but both Cks1 and Skp2 transfection strongly induced. Moreover, we
      inhibited Cks1 expression by small interference RNA (siRNA) in OSCC. Cks1 siRNA
      transfection induced p27 accumulation and inhibited the growth of OSCC cells.
      These findings suggest that Cks1 overexpression may play an important role for
      OSCC development through Skp2-mediated p27 degradation, and that Cks1 siRNA can
      be a novel modality of gene therapy.

PMID- 15579457
TI  - The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign
      body giant cell formation.
AB  - The foreign body reaction (FBR) develops in response to the implantation of
      almost all biomaterials and can be detrimental to their function. The formation
      of foreign body giant cells (FBGC), which damage the surface of biomaterials, is
      considered a hallmark of this reaction. FBGC derive from blood-borne monocytes
      that enter the implantation site after surgery in response to the release of
      chemotactic signals. In this study, we implanted biomaterials subcutaneous (s.c.)
      in mice that lack the monocyte chemoattractant CC chemokine ligand 2 (CCL2) and
      found that biomaterials were encapsulated despite reduced FBGC formation. The
      latter was due to compromised macrophage fusion rather than migration. Consistent
      with the reduction in FBGC formation, biodegradable biomaterials sustained
      reduced damage in CCL2-null mice. Furthermore, blockade of CCL2 function by
      localized gene delivery in wild-type mice hindered FBGC formation, despite normal
      monocyte recruitment. The requirement for CCL2 in fusion was confirmed by the
      ability of both a CCL2 inhibitory peptide and an anti-CCL2 Ab to reduce FBGC
      formation from peripheral blood monocytes in an in vitro assay. Our findings
      demonstrate a previously unreported involvement of CCL2 in FBGC formation, and
      suggest that FBGC are not the primary determinants of capsule formation in the
      FBR.

PMID- 15579458
TI  - Distinctive properties of human adult brain-derived myelin progenitor cells.
AB  - We used expression of the ganglioside A2B5 to isolate putative myelin progenitor
      cells from adult human central nervous system parenchyma and compared their
      phenotypic (expression of myelin lineage molecules) and functional (survival,
      proliferation) properties with mature oligodendrocytes (OLGs) derived from the
      same adult material and with A2B5(+) cells isolated from human fetal brain.
      A2B5(+) cells represented 3 to 5% of the total cell suspension derived from adult
      specimens. Results of protein (immunostaining) and RNA (polymerase chain
      reaction) analyses indicated that the adult A2B5(+) cells were more committed to
      the OLG lineage than their fetal counterparts while continuing to retain
      properties of progenitor cells compared to the postmitotic mature OLGs. Although
      the adult A2B5(+) cells retained the capacity to divide, albeit at a reduced rate
      compared to fetal A2B5(+) cells, they showed reduced survival and process
      outgrowth compared not only to fetal cells but also to mature OLGs. Our results
      confirm the presence of progenitor cells committed to the OLG lineage in the
      adult human central nervous system but raise the issues regarding the intrinsic
      capacity of these cells to contribute to the process of remyelination that may be
      necessary during demyelinating diseases.

PMID- 15579459
TI  - Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth
      factor pathway genes: therapeutic strategy for herpetic stromal keratitis.
AB  - Ocular neovascularization often results in vision impairment. Frequently vascular
      endothelial cell growth factors (VEGFs) are mainly responsible for the
      pathological neovascularization as in the case in neovascularization induced by
      CpG oligodeoxynucleotides and herpes simplex virus infection in this report.
      siRNAs targeting either VEGFA, VEGFR1, VEGFR2, or a mix of the three were shown
      to significantly inhibit neovascularization induced by CpG when given locally or
      systemically. The efficacy of systemic administration was facilitated by the use
      of a polymer delivery vehicle. Additional experiments showed a significant
      inhibitory effect of the siRNAs mix when given either locally or systemically in
      vehicle against herpes simplex virus-induced angiogenesis as well as against
      lesions of stromal keratitis. These results indicate that the use of VEGF pathway
      specific siRNAs represents a useful therapy against neovascularization-related
      eye diseases.

PMID- 15579460
TI  - Novel chemokine responsiveness and mobilization of neutrophils during sepsis.
AB  - Blood neutrophils (PMN) are usually unresponsive to CC chemokines such as
      monacyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha. In
      rodents, the lung buildup of PMN as determined by myeloperoxidase (MPO) activity
      after airway instillation of bacterial lipopolysaccharide (LPS) was independent
      of MCP-1 and MIP-1 alpha. In striking contrast, during sepsis following cecal
      ligation and puncture (CLP), blood PMN demonstrated mRNA for CC chemokine
      receptors. Furthermore, PMN from CLP, but not from sham rodents, bound MCP-1 and
      MIP-1 alpha and responded chemotactically in vitro to both MCP-1 and MIP-1 alpha.
      In CCR2(-/-) mice or WT mice treated in vivo with antibodies to either MCP-1 or
      MIP-1 alpha, MPO activity was greatly attenuated in CLP animals. In CLP mice,
      increased serum IL-6 levels were found to be dependent on CCR2, MCP-1, and MIP-1
      alpha. When PMN from CLP rodents were incubated in vitro with either MCP-1 or MIP
      1 alpha, release of IL-6 was also shown. These findings suggest that sepsis
      fundamentally alters the trafficking of PMN into the lung in a manner that now
      engages functional responses to CC chemokines.

PMID- 15579461
TI  - Modulation of nuclear factor-kappa B activity by indomethacin influences A beta
      levels but not A beta precursor protein metabolism in a model of Alzheimer's
      disease.
AB  - Epidemiological studies show that some nonsteroidal anti-inflammatory drugs,
      nonspecific inhibitors of the cyclooxygenase enzyme, reduce the incidence of
      Alzheimer's disease (AD). We determined the impact of two nonsteroidal anti
      inflammatory drugs on A beta levels, deposition, and metabolism in a mouse model
      (the Tg2576) of AD-like amyloidosis. To this end, mice were treated with
      indomethacin and nimesulide continuously from 8 months of age until they were 15
      months old. At the end of the study, indomethacin significantly reduced A beta(1
      40) and A beta(1-42) levels in both cortex and hippocampus. This decrease was
      coincidental with a significant reduction of the nuclear factor (NF)-kappa B
      activity. By contrast, nimesulide had no effect on both A beta peptides and NF
      kappa B. Consistently, mice receiving indomethacin, but no nimesulide, showed a
      significant reduction in the amyloid burden compared with placebo. Neither drug
      had an effect on plasma levels of A beta peptides or the A beta precursor protein
      metabolism. In vitro studies confirmed that genetic absence of this factor
      reduces the anti-amyloidogenic effect of indomethacin. These findings indicate
      that chronic administration of indomethacin by blocking the activation of the NF
      kappa B significantly reduces the amyloid pathology in Tg2576 mice, and provide
      insights into the mechanisms by which this drug could slow progression of AD.

PMID- 15579462
TI  - A family of acetylcholine-gated chloride channel subunits in Caenorhabditis
      elegans.
AB  - The genome of the nematode Caenorhabditis elegans encodes a surprisingly large
      and diverse superfamily of genes encoding Cys loop ligand-gated ion channels.
      Here we report the first cloning, expression, and pharmacological
      characterization of members of a family of anion-selective acetylcholine receptor
      subunits. Two subunits, ACC-1 and ACC-2, form homomeric channels for which
      acetylcholine and arecoline, but not nicotine, are efficient agonists. These
      channels are blocked by d-tubocurarine but not by alpha-bungarotoxin. We provide
      evidence that two additional subunits, ACC-3 and ACC-4, interact with ACC-1 and
      ACC-2. The acetylcholine-binding domain of these channels appears to have
      diverged substantially from the acetylcholine-binding domain of nicotinic
      receptors.

PMID- 15579463
TI  - Phosphorylation of p27Kip1 at Thr-157 interferes with its association with
      importin alpha during G1 and prevents nuclear re-entry.
AB  - We have studied mechanisms of Akt-mediated phosphorylation and regulation of
      cellular localization of p27. Akt phosphorylates Thr-157 in p27 and retains it in
      the cytosol. In cells arrested in G(1) and then synchronized to enter into S
      phase, Akt-mediated phosphorylation of Thr-157 p27 occurred in the cytosol during
      G(1) phase of the cell cycle. Both T157A and S10A p27 mutants localized in the
      nucleus in all phases of the cell cycle regardless of the expression of active
      Akt. Thr-157 phosphorylation was undetectable in S10A-p27, suggesting that Ser-10
      phosphorylation is required for p27 localization in the cytosol and subsequent
      phosphorylation at Thr-157. Phosphorylation at Thr-157 interrupted the
      association of p27 with importin alpha. A T157A-p27 mutant protein exhibited
      higher association with importin alpha than wild-type-p27. Treatment of
      transfected and endogenous p27 with alkaline phosphatase rescued its association
      with importin alpha. Leptomycin B inhibited cytosolic Thr-157 P-p27 staining,
      implying that CRM1-dependent nuclear export is required for Akt-mediated Thr-157
      phosphorylation. Heterokaryon shuttling assays with NIH3T3 (mouse) cells
      transfected with FLAG-p27 and HeLa (human) cells revealed that both wild type and
      T157A-p27 shuttled from NIH3T3 to HeLa cell nuclei with similar frequencies.
      However, S10A-p27 was found only in the NIH3T3 nuclei of NIH3T3-HeLa cell
      fusions. These results suggest that 1) Ser-10 phosphorylation is required for
      nuclear export of p27, 2) subsequent Akt-mediated phosphorylation at Thr-157
      during G(1) phase corrals p27 in the cytosol, and 3) Thr-157 phosphorylation
      inhibits the association of p27 with importin alpha thus preventing its re-entry
      into the nucleus.

PMID- 15579464
TI  - Hemoglobin receptor in Leishmania is a hexokinase located in the flagellar
      pocket.
AB  - Hb endocytosis in Leishmania is mediated through a 46-kDa protein located in the
      flagellar pocket. To understand the nature of the Hb receptor (HbR), we have
      purified the 46-kDa protein to homogeneity from Leishmania promastigote membrane.
      Purified HbR specifically binds Hb. The gene for HbR was cloned, and sequence
      analysis of the full-length HbR gene indicates the presence of hexokinase (HK)
      signature sequences, ATP-binding domain, and PTS-II motif. Four lines of evidence
      indicate that HbR in Leishmania is a hexokinase: 1) the recombinant HbR binds Hb,
      and the Hb-binding domain resides in the N terminus of the protein; 2)
      recombinant proteins and cell lysate prepared from HbR-overexpressing Leishmania
      promastigotes show enhanced HK activity in comparison with untransfected cells;
      3) immunolocalization studies using antibodies against the N-terminal fragment
      (Ld-HbR-DeltaC) of Ld-HbR indicate that this protein is located in the flagellar
      pocket of Leishmania; and 4) binding and uptake of (125)I-Hb by Leishmania is
      significantly inhibited by anti-Ld-HbR-DeltaC antibody and Ld-HbR-DeltaC,
      respectively. Taken together, these results indicate that HK present in the
      flagellar pocket of Leishmania is involved in Hb endocytosis.

PMID- 15579465
TI  - Proteomics reveal Cochlin deposits associated with glaucomatous trabecular
      meshwork.
AB  - The etiology of primary open angle glaucoma, a leading cause of age-related
      blindness, remains poorly defined, although elevated intraocular pressure (IOP)
      contributes to the disease progression. To better understand the mechanisms
      causing elevated IOP from aqueous humor circulation, we pursued proteomic
      analyses of trabecular meshwork (TM) from glaucoma and age-matched control
      donors. These analyses demonstrated that Cochlin, a protein associated with
      deafness disorder DFNA9, is present in glaucomatous but absent in normal TM.
      Cochlin was also detected in TM from the glaucomatous DBA/2J mouse preceding
      elevated IOP but found to be absent in three other mouse lines that do not
      develop elevated IOP. Histochemical analyses revealed co-deposits of Cochlin and
      mucopolysaccharide in human TM around Schlemm's canal, similar to that observed
      in the cochlea in DFNA9 deafness. Purified Cochlin was found to aggregate after
      sheer stress and to induce the aggregation of TM cells in vitro. Age-dependent in
      vivo increases in Cochlin were observed in glaucomatous TM, concomitant with a
      decrease in type II collagen, suggesting that Cochlin may disrupt the TM
      architecture and render components like collagen more susceptible to degradation
      and collapse. Overall, these observations suggest that Cochlin contributes to
      elevated IOP in primary open angle glaucoma through altered interactions within
      the TM extracellular matrix, resulting in cell aggregation, mucopolysaccharide
      deposition, and significant obstruction of the aqueous humor circulation.

PMID- 15579466
TI  - Regulation of PSGL-1 interactions with L-selectin, P-selectin, and E-selectin:
      role of human fucosyltransferase-IV and -VII.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) interactions with selectins regulate
      leukocyte migration in inflammatory lesions. In mice, selectin ligand activity
      regulating leukocyte recruitment and lymphocyte homing into lymph nodes results
      from the sum of unequal contributions of fucosyltransferase (FucT)-IV and FucT
      VII, with FucT-VII playing a predominant role. Here we have examined the role of
      human FucT-IV and -VII in conferring L-selectin, P-selectin, and E-selectin
      binding activities to PSGL-1. Lewis x (Le(x)) carbohydrate was generated at the
      CHO(dhfr)(-) cell surface by FucT-IV expression, whereas sialyl Le(x) (sLe(x))
      was synthesized by FucT-VII. Both human FucT-IV and -VII had the ability to
      generate carbohydrate ligands that support L-selectin-, P-selectin-, and E
      selectin-dependent rolling on PSGL-1, with FucT-VII playing a major role.
      Cooperation was observed between FucT-IV and -VII in recruiting L-, P-, or E
      selectin-expressing cells on PSGL-1 and in regulating cell rolling velocity and
      stability. Additional rolling adhesion assays were performed to assess the role
      of Thr-57-linked core-2 O-glycans in supporting L-selectin-, P-selectin-, and E
      selectin-dependent rolling on PSGL-1. These studies confirmed that core-2 O
      glycans attached to Thr-57 play a critical role in supporting L- and P-selectin
      dependent rolling and revealed that additional binding sites support >75% of E
      selectin-mediated rolling. The observations presented here indicate that human
      FucT-IV and -VII both contribute and cooperate in regulating L-selectin-, P
      selectin-, and E-selectin-dependent rolling on PSGL-1, with FucT-VII playing a
      predominant role in conferring selectin binding activity to PSGL-1.

PMID- 15579467
TI  - Reversible oxidation of ERK-directed protein phosphatases drives oxidative
      toxicity in neurons.
AB  - Oxidative stress links diverse neuropathological conditions that include stroke,
      Parkinson's disease, and Alzheimer's disease and has been modeled in vitro with
      various paradigms that lead to neuronal cell death following the increased
      accumulation of reactive oxygen species. For example, immortalized neurons and
      immature primary cortical neurons undergo cell death in response to depletion of
      the antioxidant glutathione, which can be elicited by administration of glutamate
      at high concentrations. We have demonstrated previously that this glutamate
      induced oxidative toxicity requires activation of the mitogen-activated protein
      kinase member ERK1/2, but the mechanisms by which this activation takes place in
      oxidatively stressed neurons are still not fully known. In this study, we
      demonstrate that during oxidative stress, ERK-directed phosphatases of both the
      serine/threonine- and tyrosine-directed classes are selectively and reversibly
      inhibited via a mechanism that is dependent upon the oxidation of cysteine
      thiols. Furthermore, the impact of ERK-directed phosphatases on ERK1/2 activation
      and oxidative toxicity in neurons was tested in a neuronal cell line and in
      primary cortical cultures. Overexpression of the highly ERK-specific phosphatase
      MKP3 and its catalytic mutant, MKP3 C293S, were neuroprotective in transiently
      transfected HT22 cells and primary neurons. The neuroprotective effect of the
      MKP3 C293S mutant, which enhances ERK1/2 phosphorylation but blocks its nuclear
      translocation, demonstrates the necessity for active ERK1/2 nuclear localization
      for oxidative toxicity in neurons. Together, these data implicate the inhibition
      of endogenous ERK-directed phosphatases as a mechanism that leads to aberrant
      ERK1/2 activation and nuclear accumulation during oxidative toxicity in neurons.

PMID- 15579468
TI  - A Rac1/phosphatidylinositol 3-kinase/Akt3 anti-apoptotic pathway, triggered by
      AlsinLF, the product of the ALS2 gene, antagonizes Cu/Zn-superoxide dismutase
      (SOD1) mutant-induced motoneuronal cell death.
AB  - AlsinLF, the product of the ALS2 gene, inhibits Cu/Zn-superoxide dismutase (SOD1)
      mutant-induced neurotoxicity via its Rho guanine nucleotide-exchanging factor
      domain. We here identified Rac1, a Rho family small GTPase, as a target for the
      Rho guanine nucleotide-exchanging factor activity of alsinLF. Rac1 associates
      with alsinLF. The amount of the GTP form of Rac1 is up-regulated by enforced
      overexpression of alsinLF. We further found not only that constitutively active
      Rac1 suppresses motoneuronal cell death induced by SOD1 mutants but also that the
      neuroprotective activity of alsinLF was completely inhibited by knocking down the
      endogenous Rac1 expression with small interfering RNA for Rac1, indicating that
      Rac1 is the major effector for alsinLF-mediated neuroprotection. Such
      alsinLF/Rac1-mediated neuroprotection occurs specifically against the SOD1 mutant
      induced cell death but not against the cell death induced by any other neurotoxic
      insults in motoneuronal NSC34 cells. We further demonstrated that the
      alsinLF/Rac1-mediated neuroprotective signal is transmitted to the
      phosphatidylinositol 3-kinase/Akt anti-apoptotic axis. Among three Akt family
      proteins, Akt3 is the major downstream mediator for alsinLF/Rac1-mediated
      neuroprotection, which is specifically effective against SOD1 mutant-induced
      neurotoxicity.

PMID- 15579469
TI  - Ultraviolet irradiation induces Smad7 via induction of transcription factor AP-1
      in human skin fibroblasts.
AB  - Smad7 functions as an endogenous negative regulator of transforming growth factor
      beta (TGF-beta)/SMAD signaling. The TGF-beta/SMAD pathway is a major regulator of
      collagen production in connective tissue. Reduced expression of SMAD7 has been
      reported in TGF-beta-mediated fibrotic diseases, characterized by overproduction
      of collagen. Solar ultraviolet (UV) irradiation reduces collagen production by
      fibroblasts in human skin in vivo. We have investigated regulation of Smad7 gene
      expression by UV irradiation in human skin fibroblasts. UV irradiation
      transiently increased SMAD7 mRNA and protein levels. Induction of SMAD7 mRNA and
      protein was maximal within 5 h and returned to initial basal levels 24 h post-UV
      irradiation. UV irradiation induced Smad7 promoter-reporter activity 3-fold. The
      Smad7 promoter contains functional enhancer sequences that bind transcription
      factors SMAD3 and activator protein-1 (AP-1). UV irradiation reduced protein
      binding to the Smad3 enhancer and increased binding to the AP-1 enhancer.
      Deletion of the AP-1 binding site in the Smad7 promoter completely abolished UV
      stimulation of SMAD7 transcription. Deletion of the Smad3 element had no effect
      on UV irradiation-induced promoter activity. UV irradiation increased mRNA and
      protein expression of the AP-1 family members, c-Jun and c-Fos, which bound to
      the AP-1 element in the Smad7 promoter. Furthermore, overexpression of dominant
      negative c-Jun substantially reduced UV irradiation induction of SMAD7
      transcription. These data demonstrate that induction of Smad7 gene expression by
      UV irradiation is mediated via induction of the transcription factor AP-1 in
      human skin fibroblasts.

PMID- 15579470
TI  - Srcasm modulates EGF and Src-kinase signaling in keratinocytes.
AB  - The Src-activating and signaling molecule (Srcasm) is a recently described
      activator and substrate of Src-family tyrosine kinases (SFKs). When
      phosphorylated at specific tyrosines, Srcasm associates with Grb2 and p85, the
      regulatory subunit of phosphoinositide 3-kinase; however, little is known about
      the role of Srcasm in cellular signaling. Data presented here demonstrate that
      epidermal growth factor (EGF) receptor ligands promote the tyrosine
      phosphorylation of endogenous and adenovirally transduced Srcasm in
      keratinocytes, and that increased levels of Srcasm activate endogenous SFKs, with
      a preference for Fyn and Src. In addition, Srcasm potentiates EGF-dependent
      signals transmitted by SFKs in keratinocytes. Tyrosine phosphorylation of Srcasm
      is dependent on growth factors and the activity of EGFR and SFKs. Increased
      Srcasm expression enhances p44/42 mitogen-activated protein kinase activity and
      Elk-1-dependent transcriptional events. Elevated Srcasm levels inhibit
      keratinocyte proliferation while promoting specific aspects of keratinocyte
      differentiation. Lastly, Srcasm levels are decreased in human cutaneous
      neoplasia. Collectively, these data demonstrate that Srcasm plays a role in
      linking EGF receptor- and SFK-dependent signaling to differentiation in
      keratinocytes.

PMID- 15579471
TI  - A novel stress-induced EDEM variant regulating endoplasmic reticulum-associated
      glycoprotein degradation.
AB  - Proteins expressed in the endoplasmic reticulum (ER) are subjected to a tight
      quality control. Persistent association with ER-resident molecular chaperones
      prevents exit of misfolded or incompletely assembled polypeptides from the ER and
      forward transport along the secretory line. ER-associated degradation (ERAD) is
      in place to avoid ER constipation. Folding-incompetent products have to be
      identified to interrupt futile folding attempts and then targeted for unfolding
      and dislocation into the cytosol for proteasome-mediated destruction. These
      processes are better understood for N-glycosylated proteins that represent the
      majority of polypeptides expressed in the ER. EDEM, a mannosidase-like chaperone,
      regulates the extraction of misfolded glycoproteins from the calnexin cycle. Here
      we identify and characterize EDEM2, a novel, stress-regulated mannosidase-like
      protein that operates in the ER lumen. We show that transcriptional up-regulation
      of EDEM2 depends on the ER stress-activated transcription factor Xbp1, that EDEM2
      up-regulation selectively accelerates ERAD of terminally misfolded glycoproteins
      by facilitating their extraction from the calnexin cycle, and that the previously
      characterized homolog EDEM is also a soluble protein of the ER lumen in HEK293
      cells.

PMID- 15579472
TI  - Characterization of a 5'-polynucleotide kinase/3'-phosphatase from bacteriophage
      RM378.
AB  - A polynucleotide kinase from the thermophilic bacteriophage RM378 that infects
      the thermophilic eubacterium Rhodothermus marinus was identified, expressed, and
      purified. This polynucleotide kinase was demonstrated to have a 5'-kinase domain
      as well as a 3'-phosphohydrolase domain. The RM378 polynucleotide kinase had
      limited sequence similarity to the 5'-kinase domain of the T4 bacteriophage
      polynucleotide kinase, but apparent homology was not evident within the 3'
      phosphohydrolase domain. The domain order of RM378 polynucleotide kinase was
      reversed relative to that of the T4 polynucleotide kinase. The RM378
      phosphohydrolase domain displayed some sequence similarity with the bacterial
      poly(A) polymerase family, including an HD motif characteristic of the diverse
      superfamily of metal-dependent HD phosphohydrolases. The RM378 polynucleotide
      kinase was biochemically characterized and shown to possess 5'-kinase activity on
      RNA and single- and double-stranded DNA at elevated temperatures. It also showed
      phosphohydrolase activity on 2':3'-cyclic adenosine monophosphate. This
      description of the RM378 polynucleotide kinase, along with the recently described
      RM378 RNA ligase, suggests that the RM378 bacteriophage has to counter a similar
      anti-phage mechanism in R. marinus as the one that the T4 phage has to counter in
      Escherichia coli.

PMID- 15579473
TI  - GSH inhibits trypsinization of the C-terminal half of human MRP1.
AB  - MRP1 is a 190-kDa membrane glycoprotein that confers multidrug resistance to
      tumor cells. The accumulated evidence has proved that GSH interacts with MRP1 and
      stimulates drug transport. However, the mechanism of GSH-dependent drug transport
      by MRP1 remains unclear. In this study, we used limited tryptic digestion of MRP1
      in isolated membrane vesicles, in the presence and absence of GSH, to investigate
      the influence of GSH on MRP1 conformation. We found that GSH inhibited the
      generation of an approximately 35-kDa C-terminal tryptic fragment (including a C
      terminal His tag) termed C2 from MRP1. This effect of GSH was not because of
      direct inhibition of trypsin activity, and agosterol A enhanced the inhibitory
      effect of GSH. The main cleavage site in MRP1 for the generation of the C2
      fragment by trypsin resided between TMD2 and NBD2 of MRP1. Limited tryptic
      digestion of membrane vesicles expressing various truncated and co-expressed MRP1
      fragments in the presence and absence of GSH revealed that GSH inhibited the
      production of the C2 fragment only in the presence of the L(0) region of MRP1.
      Thus the L(0) region is required for the inhibition of trypsinization of the C
      terminal half of MRP1 by GSH. These findings, together with previous reports,
      suggest that GSH induces a conformational change at a site within the MRP1 that
      is indispensable for the interaction of MRP1 with its substrates.

PMID- 15579475
TI  - The Venus Fly Trap domain of the extracellular Ca2+ -sensing receptor is required
      for L-amino acid sensing.
AB  - We previously demonstrated that the human calcium-sensing receptor (CaR) is
      allosterically activated by L-amino acids (Conigrave, A. D., Quinn, S. J., and
      Brown, E. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 4814-4819). However, the
      domain-based location of amino acid binding has been uncertain. We now show that
      the Venus Fly Trap (VFT) domain of CaR, but none of its other major domains, is
      required for amino acid sensing. Several constructs were informative when
      expressed in HEK293 cells. First, the wild-type CaR exhibited allosteric
      activation by L-amino acids as previously observed. Second, two CaR-mGlu chimeric
      receptor constructs that retained the VFT domain of CaR, one containing the
      extracellular Cys-rich region of CaR and the other containing the Cys-rich region
      of the rat metabotropic glutamate type-1 (mGlu-1) receptor, together with the rat
      mGlu-1 transmembrane region and C-terminal tail, retained amino acid sensing.
      Third, a CaR lacking residues 1-599 of the N-terminal extracellular head but
      retaining an intact CaR transmembrane region and a functional but truncated C
      terminus (headless-T903 CaR) failed to respond to L-amino acids but retained
      responsiveness to the type-II calcimimetic NPS R-467. Finally, a T903 CaR control
      that retained an intact N terminus also retained L-amino acid sensing. Taken
      together, the data indicate that the VFT domain of CaR is necessary for L-amino
      acid sensing and are consistent with the hypothesis that the VFT domain is the
      site of L-amino acid binding. The findings support the concept that the mGlu-1
      amino acid binding site for L-glutamate is conserved as an L-amino acid binding
      site in its homolog, the CaR.

PMID- 15579476
TI  - A proteomic analysis of lysosomal integral membrane proteins reveals the diverse
      composition of the organelle.
AB  - Lysosomes are endocytic subcellular compartments that contribute to the
      degradation and recycling of cellular material. Using highly purified rat liver
      tritosomes (Triton WR1339-filled lysosomes) and an ion exchange chromatography/LC
      tandem MS-based protein/peptide separation and identification procedure, we
      characterized the major integral membrane protein complement of this organelle.
      While many of the 215 proteins we identified have been previously associated with
      lysosomes and endosomes, others have been associated with the endoplasmic
      reticulum, Golgi, cytosol, plasma membrane, and lipid rafts. At least 20 proteins
      were identified as unknown cDNAs that have no orthologues of known function, and
      35 proteins were identified that function in protein and vesicle trafficking.
      This latter group includes multiple Rab and SNARE proteins as well as ubiquitin.
      Defining the roles of these proteins in the lysosomal membrane will assist in
      elucidating novel lysosomal functions involved in cellular homeostasis and
      pathways that are affected in various disease processes.

PMID- 15579477
TI  - Chaperones for intimate examinations: cross sectional survey of attitudes and
      practices of general practitioners.

PMID- 15579478
TI  - Implementation of recommendations for the care of children in UK emergency
      departments: national postal questionnaire survey.

PMID- 15579479
TI  - Case-control analysis of thymidylate synthase polymorphisms and risk of lung
      cancer.
AB  - Although tobacco smoking is the primary risk factor for lung cancer, low dietary
      folate intake and suboptimal DNA repair capacity also contribute to lung cancer
      risk. Thymidylate synthase (TYMS) is involved in the metabolism of folate and the
      provision of nucleotides needed for DNA synthesis and repair. Thus, a variation
      in TYMS functions likely plays a role in the etiology of lung cancer. The TYMS
      gene has a tandem repeat polymorphism (two or three 28 bp) in the TYMS enhancer
      region (TSER) and a 6 bp deletion/insertion polymorphism in the TS 3'
      untranslated region (TS3'UTR or 1494del6). We investigated the frequencies of
      these two polymorphisms in a hospital-based case-control study of 1055 lung
      cancer patients and 1140 cancer-free controls in a non-Hispanic white population
      and genotyped for these two polymorphisms. We found that the TS3'UTR, but not the
      TSER, variant was associated with the risk of lung cancer. Compared with
      homozygotes for the TS3'UTR 6 bp deletion (0bp/0bp), the 6bp/0bp+6bp/6bp
      genotypes were associated with a significantly increased risk of lung cancer
      [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.12-2.06]. In
      stratification analysis the risk associated with the 0bp/6bp+6bp/6bp genotype was
      more pronounced in subjects who were >55 years old (OR = 1.57, 95% CI = 1.10
      2.23), males (OR = 1.88, 95% CI = 1.22-2.89), current (OR = 2.04, 95% CI = 1.26
      3.29) and heavy smokers (OR = 1.73, 95% CI = 1.10-2.70) and current drinkers (OR
      = 3.17, 95% CI = 1.78-5.64).Furthermore, significant gene-dietary interactions
      were found between TS3'UTR and alcohol consumption and between TSER and vitamin
      B(12) intake. In conclusion, the polymorphisms of TYMS are likely to contribute
      to the risk of lung cancer in non-Hispanic whites and interact with dietary
      factors in lung cancer development.

PMID- 15579480
TI  - Meat intake, cooking-related mutagens and risk of colorectal adenoma in a
      sigmoidoscopy-based case-control study.
AB  - Reported habits of red meat consumption, particularly red meat that has been
      cooked to the degree termed 'well-done', is a positive risk factor for colorectal
      cancer. Under high, pyrolytic temperatures, heterocyclic amines (HCA) and
      benzo[a]pyrene (BP) molecules can form inside and on the surface of red meat,
      respectively. These compounds are precursors that are metabolically converted to
      compounds known to act as mutagens and carcinogens in animal models, yet their
      role in human colorectal carcinogenesis remains to be clarified. We investigated
      whether intake of these compounds is associated with risk of colorectal adenoma
      in the context of a polyp-screening study conducted in Southern California. Using
      a database of individual HCAs and BP in meats of various types and subjected to
      specified methods and degrees of cooking, we estimated nanogram consumption of 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,4,8-trimethylimidazo[4,5
      f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and benzo[a]pyrene
      (BP). We observed a 6% increased risk of large (>1 cm) adenoma per 10 ng/day
      consumption of BP [OR = 1.06 (95% CI, 1.00-1.12), P (trend) = 0.04]. A major
      source of BP is red meat exposed to a naked flame, as occurs during the
      barbecuing process. Consistent with this finding an incremental increase of 10 g
      of barbecued red meat per day was associated with a 29% increased risk of large
      adenoma [OR = 1.29 (95% CI, 1.02-1.63), P (trend) = 0.04]. Individuals in the top
      quintile of barbecued red meat intake were at increased risk of large adenoma [OR
      = 1.90 (95% CI, 1.04-3.45)], compared with never consuming barbecued red meat.
      The consumption of oven-broiled red meat was inversely related to adenoma risk
      compared with non-consumers [OR = 0.49 (95% CI, 0.28-0.85)]. We did not identify
      any association with consumption of individual HCAs and colorectal adenoma risk.
      These results support the hypothesis that BP contributes to colorectal
      carcinogenesis.

PMID- 15579481
TI  - Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor
      necrosis factor {alpha} and risk of gastric cancer in a Chinese population.
AB  - Helicobacter pylori infection and the cytokine-mediated inflammatory responses
      play important roles in gastric cancer pathogenesis. This case control study was
      conducted to assess the association between genetic polymorphisms in interleukin
      (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor alpha (TNFalpha), which
      are involved in H.pylori infection, and risk of gastric cancer. Genotypes were
      determined by PCR-based denaturing high-performance liquid chromatography
      analysis and direct DNA sequencing in 250 incident cases with gastric cancer and
      300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and
      IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori
      infection. We found that the risk of gastric cancer was significantly elevated in
      subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence
      interval (CI) 1.27-3.21] or IL-10-1082 G (OR 2.02; 95% CI 1.24-3.29) or TNFalpha
      308 AG (OR 1.81; 95% CI 1.04-3.14) genotype. An elevated risk of gastric cancer
      was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR
      2.54; 95% CI 1.38-4.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.42-4.93). An
      increased OR was also suggested for IL-1B-31 and TNFalpha-238, but confidence
      intervals included the null value. There was no evidence of increased risk for
      any of the other polymorphisms evaluated. These findings suggest that genetic
      polymorphisms in IL-8, IL-10 and TNFalpha may play important roles in developing
      gastric cancer in the Chinese population.

PMID- 15579482
TI  - Effects of 8-methoxypsoralen on cytochrome P450 2A13.
AB  - Cytochrome P450 2A13 efficiently catalyzes the bioactivation of several tobacco
      specific nitrosamines in vitro. This efficient bioactivation together with the
      selective expression of P450 2A13 in the human lung suggests that this P450 may
      play an important role in the initiation of lung cancer in smokers. Therefore,
      the identification of potent and selective inhibitors/inactivators of P450 2A13
      could potentially help to lower the risk of lung cancer in smokers. In this
      study, we investigated the ability of 8-methoxypsoralen (8-MOP), a known
      inhibitor of P450 2A6, to inhibit and inactivate the activities of heterologously
      expressed P450 2A13 in reconstituted systems. We found that 8-MOP is a potent
      inhibitor of P450 2A13-mediated metabolism of several compounds, including
      testosterone, which had not been known to be a P450 2A13 substrate. The K(I) for
      the non-competitive inhibition of P450 2A13-mediated coumarin 7-hydroxylation by
      8-MOP was 0.11 microM. The inhibition of P450 2A13 was accompanied by
      inactivation of the enzyme. Therefore, the observed decrease in activity is most
      likely due to the inactivation of the enzyme together with competitive or non
      competitive inhibition of P450 2A13 by 8-MOP. The inactivation did not result in
      a loss of native heme, or a significant change in the reduced-CO spectrum of the
      P450, and did not generate any detectable heme adducts. Instead, the inactivation
      of P450 2A13 by8-MOP occurred through the formation of an adduct to the
      apoprotein. LC/MS analysis of the adducted protein indicated an increase in the
      mass of 232 Da compared with the unadducted protein. This mass shift correlates
      with the addition of one molecule of 8-MOP plus one atom of oxygen atom to the
      P450 apoprotein.

PMID- 15579483
TI  - Modulation of tumor formation and intestinal cell migration by estrogens in the
      Apc(Min/+) mouse model of colorectal cancer.
AB  - Epidemiological studies suggest that post-menopausal hormone replacement therapy
      (HRT) reduces colorectal cancer (CRC) incidence. Phytoestrogens, including the
      soy isoflavone genistein and coumestrol, are used by many women as alternatives
      to HRT. Previous studies showed that ovariectomy induced a 77% increase in
      intestinal adenoma number in the C57BL/6J-Min/+ (Min/+) mouse, an animal model of
      adenomatous polyposis coli (APC)-associated CRC. Replacement of estradiol (E(2))
      in ovariectomized Min/+ mice reduced tumor number to baseline and up-regulated
      the expression of estrogen receptor beta (ERbeta). We hypothesized that the
      phytoestrogens genistein and coumestrol would inhibit intestinal tumorigenesis in
      ovariectomized Min/+ mice. Min/+ and Apc(+/+) (WT) mice were ovariectomized and
      assigned to either a control diet or treatment with E(2), genistein or
      coumestrol. Treatment of ovariectomized Min/+ (Min/+ OX) mice with genistein
      resulted in a non-significant reduction in tumor number. Min/+ OX mice treated
      with coumestrol had significantly fewer tumors than untreated Min/+ OX controls
      and the same number of tumors as non-ovariectomized Min/+ mice. Bromodeoxyuridine
      migration assays also demonstrated that treatment with E(2) or coumestrol
      improved enterocyte migration rate. Immunoprecipitation and immunohistochemistry
      analyses showed that impaired association of the adherens junction proteins E
      cadherin and beta-catenin in Min/+ mice was improved by treatment with either
      E(2) or coumestrol. Immunoblot analyses also showed that expression of ERbeta was
      elevated in enterocytes of Min/+ OX mice treated with E(2) or coumestrol as
      compared with those of untreated Min/+ OX mice. In conclusion, both coumestrol
      and E(2) prevent intestinal tumorigenesis and ameliorate enterocyte migration and
      intercellular adhesion in the Apc(Min/+) mouse model of CRC.

PMID- 15579484
TI  - Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in
      gastric cancer.
AB  - Aspirin-induced apoptosis is one of the important mechanisms for its antitumour
      effect against gastric cancer. We aimed at investigating the involvement of bcl-2
      family members in the apoptotic pathway in gastric cancer. Gastric cancer cell
      line AGS and MKN-45 were observed as to cell growth inhibition and induction of
      apoptosis in response to treatment with aspirin. Cell proliferation was measured
      by MTT assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole staining.
      Protein expression was determined by western blotting. We showed that aspirin
      activated caspase-8, caspase-9 and capase-3, cleaved and translocated Bid,
      induced a conformational change in and translocation of Bax and cytochrome c
      release. In addition, suppression of caspase-8 with the specific inhibitor z-IETD
      fmk, as well as the pan-caspase inhibitor z-VAD-fmk, prevented Bid cleavage and
      subsequent apoptosis. The caspase inhibitors failed to abolish the effects on Bax
      activation. In conclusion, our results identify a role of caspase-8/Bid and
      activation of Bax as a novel mechanism for aspirin-induced apoptosis in gastric
      cancer.

PMID- 15579485
TI  - Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke
      inhalation and their exacerbation by high dietary levels of vitamins C and E.
AB  - The development of effective chemopreventive agents against cigarette smoke
      induced lung cancer could be greatly facilitated by the availability of suitable
      laboratory animal models. Here we report that male Hartley guinea pigs treated
      with cigarette smoke by inhalation twice a day for 28 days developed
      preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and
      squamous metaplasia, analogous to those found in human smokers. The lesions were
      accompanied by increased expression of proliferating cell nuclear antigen and
      activation of the serine/threonine kinase Akt in the bronchial epithelium. In
      contrast, no lung lesions were found in guinea pigs ('sham smoked') that were
      submitted to identical procedures but without cigarettes. Compared with a diet
      low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C
      (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of
      these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p-XSC),
      a synthetic chemopreventive organoselenium compound, in the high vitamin C-high
      vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the
      lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful
      green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no
      effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and
      the adrenal glands were significantly decreased by cigarette smoke inhalation.
      These results identify a relevant in vivo laboratory model of cigarette smoke
      induced lung cancer, suggest that p-XSC may have activity as a chemopreventive
      agent against cigarette smoke-induced lung lesions and provide additional
      evidence that very high dietary levels of certain antioxidants can have co
      carcinogenic activity in cigarette smoke-induced lung cancer.

PMID- 15579486
TI  - Upper airway obstruction as a result of massive subcutaneous emphysema following
      accidental removal of an intercostal drain.
AB  - A case is described of extensive subcutaneous emphysema with rapid and life
      threatening airway obstruction. The incident followed inadvertent removal of a
      chest drain in a patient with a persistent air leak from an iatrogenic
      pneumothorax. The pneumothorax had developed during pacemaker insertion.

PMID- 15579487
TI  - Influence of anaesthetic and analgesic techniques on outcome after surgery.
AB  - Postoperative symptoms and complications can be prevented by a suitable choice of
      anaesthetic and analgesic technique for specific procedures. The aim of analgesic
      protocols is not only to reduce pain intensity but also to decrease the incidence
      of side-effects from analgesic agents and to improve patient comfort. Moreover,
      adequate pain control is a prerequisite for the use of rehabilitation programmes
      to accelerate recovery from surgery. Thus, combining opioid and/or non-opioid
      analgesics with regional analgesic techniques not only improves analgesic
      efficacy but also reduces opioid demand and side-effects such as nausea and
      vomiting, sedation, and prolongation of postoperative ileus. Although all
      attempts to demonstrate that regional anaesthesia and analgesia decrease
      postoperative mortality are unsuccessful, there is evidence supporting a
      reduction in pulmonary complications after major abdominal surgery, and an
      improvement in patient rehabilitation after orthopaedic surgery. When such
      techniques are used, cost-benefit analysis should be considered to determine
      suitable analgesic protocols for specific surgical procedures.

PMID- 15579488
TI  - Recent advances in postoperative pain therapy.

PMID- 15579489
TI  - Deep venous thrombosis revealed during ultrasound-guided femoral nerve block.
AB  - Ultrasound imaging used to facilitate performance of a femoral nerve block also
      affords imaging of adjacent anatomical structures. Following a fracture of the
      femur, an ultrasound guided femoral nerve block (UGFNB) was performed to provide
      analgesia; this led to the incidental finding of a previously undiagnosed femoral
      vein thrombosis (DVT), resulting in a change in patient management before
      surgery. An inferior vena cava (IVC) filter was placed before intramedullary
      nailing of the fracture.

PMID- 15579490
TI  - Negatively charged purification tags for selective anion-exchange recovery.
AB  - A novel strategy for the highly selective purification of recombinant fusion
      proteins using negatively charged protein domains, which were constructed by
      protein design, is described. A triple alpha-helical domain of 58 amino acids was
      used as scaffold. Far-ultraviolet circular dichroism measurements showed that the
      designed domains had very low alpha-helicity in a low-conductivity environment in
      contrast to the scaffold. The secondary structure could be induced by adding
      salt, giving a structure comparable to the parental molecule. Further studies
      showed that the new domains were able to bind to an anion exchanger even at pH
      values down to 5 and 6. Gene fusions between one of the designed domains and
      different target proteins, such as green fluorescent protein (GFP), maltose
      binding protein (MBP) and firefly luciferase, were also constructed. These gene
      products could be efficiently purified from whole cell lysates at pH 6 using
      anion-exchange chromatography.

PMID- 15579491
TI  - mRNA analysis of several components of the plasminogen activator and matrix
      metalloproteinase systems in endometriosis using a real-time quantitative RT-PCR
      assay.
AB  - BACKGROUND: The plasminogen activator (PA) and matrix metalloproteinase (MMP)
      systems are implicated in the establishment of endometriosis. The mechanisms by
      which these systems are involved in the pathogenesis of this disease are not well
      defined and controversial results have been published. The aim of this study was
      to analyse mRNA and protein levels of several components of the PA and MMP
      systems in endometriotic tissue and endometrium from women with and without
      endometriosis. METHODS AND RESULTS: Real-time quantitative RT-PCR assays were
      developed to quantify mRNA levels of these components in 57 women with
      endometriosis and 32 controls. Endometrium of women with endometriosis showed
      higher mRNA and antigenic levels of urokinase type-PA (uPA) and MMP-3 than
      endometrium from controls. In these patients, ovarian endometriotic tissue had
      higher mRNA and antigenic levels of PA inhibitor type 1 (PAI-1) and MMP inhibitor
      type 1 (TIMP-1) than endometrium. CONCLUSIONS: The increase in mRNA and protein
      levels of uPA and MMP-3 observed in endometrium of women with endometriosis may
      facilitate the attachment of endometrial tissue to the peritoneum and ovarian
      surface, as well as the invasion of the extracellular matrix. This process would
      lead to the formation of early endometriotic lesions. Once the ovarian
      endometriotic cyst is developed, PAI-1 and TIMP-1 would increase which could
      explain the frequent clinical finding of an endometrioma without invasion of the
      adjacent ovarian tissue.

PMID- 15579492
TI  - Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic
      acid 3'-carbamoyl-biphenyl-3-yl ester (URB597): effects on anandamide and
      oleoylethanolamide deactivation.
AB  - Fatty acid amide hydrolase (FAAH) is an intracellular serine enzyme that
      catalyzes the hydrolysis of bioactive fatty acid ethanolamides such as anandamide
      and oleoylethanolamide (OEA). Genetic deletion of the faah gene in mice elevates
      brain anandamide levels and amplifies the effects of this endogenous cannabinoid
      agonist. Here, we show that systemic administration of the selective FAAH
      inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester; 0.3
      mg/kg i.p.) increases anandamide levels in the brain of rats and wild-type mice
      but has no such effect in FAAH-null mutants. Moreover, URB597 enhances the
      hypothermic actions of anandamide (5 mg/kg i.p.) in wild-type mice but not in
      FAAH-null mice. In contrast, the FAAH inhibitor does not affect anandamide or OEA
      levels in the rat duodenum at doses that completely inhibit FAAH activity. In
      addition, URB597 does not alter the hypophagic response elicited by OEA (5 and 10
      mg/kg i.p.), which is mediated by activation of peroxisome proliferator-activated
      receptor type-alpha. Finally, exogenously administered OEA (5 mg/kg i.p.) was
      eliminated at comparable rates in wild-type and FAAH-/- mice. Our results
      indicate that URB597 increases brain anandamide levels and magnifies anandamide
      responses by inhibiting intracellular FAAH activity. The results also suggest
      that an enzyme distinct from FAAH catalyzes OEA hydrolysis in the duodenum, where
      this lipid substance acts as a local satiety factor.

PMID- 15579493
TI  - Lymphatic absorption is the primary contributor to the systemic availability of
      epoetin Alfa following subcutaneous administration to sheep.
AB  - The contribution of the lymphatics to the absorption and systemic availability of
      recombinant human epoetin alfa (rHuEPO) following s.c. injection was examined
      using a cannulated sheep model. Parallel studies were conducted in sheep where a
      single bolus dose was administered either by i.v. (10, 100, or 1000 IU/kg) or
      s.c. (400 IU/kg) injection. The first s.c. group served as a control for the
      calculation of absolute bioavailability. In the second group, the efferent
      popliteal lymphatic duct was cannulated and peripheral lymph draining the
      injection site was continuously collected. In the third group, the thoracic duct
      was cannulated to allow collection of central lymph just prior to entry into the
      systemic circulation. Blood was periodically sampled from all animals, and
      concentrations in serum and lymph were determined by enzyme-linked immunosorbent
      assay. The cumulative amount of rHuEPO recovered in peripheral and central lymph
      was 83.9 +/- 6.6% and 75.3 +/- 3.9% of the administered dose, respectively,
      indicating almost complete absorption from the s.c. injection site and minimal
      clearance during transit through the lymphatic system. After i.v. administration,
      the systemic clearance of rHuEPO decreased with increasing dose, reflecting
      capacity-limited elimination kinetics. A pharmacokinetic model was developed to
      simultaneously fit experimental data for all treatment groups and estimate
      bioavailability. The direct measurement of >75% of the dose in peripheral and
      central lymph independently verifies the calculated bioavailability of 87% and
      demonstrates the major role of the lymphatic route in the overall s.c.
      bioavailability of rHuEPO after s.c. administration with this animal model.

PMID- 15579494
TI  - Free exchange across cells, and echistatin-sensitive membrane target for the
      metastasis inhibitor NAMI-A (imidazolium trans-imidazole dimethyl sulfoxide
      tetrachlororuthenate) on KB tumor cells.
AB  - The duration of cell proadhesive effects induced by imidazolium trans-imidazole
      dimethyl sulfoxide tetrachlororuthenate (NAMI-A), a compound endowed with in vivo
      antimetastatic properties, was tested in vitro on the human epithelial tumor cell
      line KB. The intensity of proadhesive effects continues to increase up to 48 to
      72 h after NAMI-A withdrawal and declines only after 96 h. The proadhesive effect
      on cells seeded on fibronectin is greater than on plastic, since it already
      reaches its maximum after 24 h. This effect suggests a role for integrin
      activation, which is further stressed by the inhibitory activity of the
      disintegrin molecule echistatin. The intensity and duration of NAMI-A's
      proadhesive effects are correlated to cell exposure time and to the rapid release
      of NAMI-A metabolites in the culture medium in the first 5 min after drug
      withdrawal. These metabolites are probably neutral species with ruthenium-bound
      bioligands to allow for the rapid exchange between cells and extracellular
      medium. These data suggest a long-lasting effect of NAMI-A in biological systems,
      even at very low concentrations, and stress the low and reversible effects on
      kidney, where it naturally concentrates. These data on proadhesive effects are,
      further, relevant for in vivo antimetastatic effects, as this adhesion is
      associated to cell motility and invasion, which in turn are related to tumor
      malignancy and metastasis.

PMID- 15579495
TI  - Mechanisms involved in the enhancement of allergic airways neutrophil influx by
      permanent C-fiber degeneration in rats.
AB  - This study was undertaken to clarify the mechanisms by which C-fiber degeneration
      at neonatal stages exacerbates the inflammatory responses of rat airways. Rats
      were treated with capsaicin at neonatal stages and immunized with ovalbumin (OVA)
      at adult ages. Challenge of capsaicin-pretreated rats with OVA promoted a higher
      influx of neutrophils in bronchoalveolar lavage (BAL) fluid compared with the
      vehicle group. No significant differences were found for the other cell types.
      The increased adhesion of N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1
      microM)- and phorbol myristate acetate (PMA; 1 microM)-treated neutrophils to
      fibronectin-coated wells did not differ among vehicle- and capsaicin-pretreated
      rats. Additionally, fMLP (10 microM), platelet-activating factor (0.1 microM),
      and substance P (50 microM) induced a significant neutrophil chemotaxis, but no
      differences were found among vehicle and capsaicin groups. Increased levels of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and leukotriene B4
      in BAL fluid as well as higher expression of cytokine-induced neutrophil
      chemoattractant (CINC)-3 in lung homogenates were detected in the capsaicin group
      compared with vehicle group. In the capsaicin group, chronic treatment with
      compound 48/80 restored the TNF-alpha levels to control values and prevented the
      neutrophil influx in BAL fluid. The enhanced production of TNF-alpha, superoxide
      anion, and nitrite by isolated alveolar macrophages in response to
      lipopolysaccharide (3 microg/ml), PMA (10 nM), and/or zymosan (100
      particles/cell) did not differ between vehicle- and capsaicin-pretreated rats. In
      conclusion, chronic neuropeptide depletion promoted by neonatal capsaicin
      treatment up-regulates airways mast cells, which upon activation by antigen at
      adult ages, release large amounts of cytokines such as TNF-alpha and CINC-3 that
      accounts for the massive airways neutrophil infiltration.

PMID- 15579496
TI  - Antagonist efficacy in MORS196L mutant is affected by the interaction between
      transmembrane domains of the opioid receptor.
AB  - In a previous study, we demonstrated that antagonists such as naloxone or
      naltrexone acted as full agonists at the mu-opioid receptor (MOR)/delta-opioid
      receptor (DOR) chimeric receptor (mudelta2, where the DOR sequence from the first
      extracellular loop to the carboxyl terminus was spliced to the MOR sequence) when
      a conserved serine residue in transmembrane 4 (TM4) was mutated to leucine.
      However, when Ser196 in the TM4 of MOR was mutated to Leu, antagonists exhibited
      partial agonistic properties. Since molecular modeling studies suggested
      transmembrane movement during receptor activation, the observed partial agonistic
      properties could be due to TM1 and TM7 interaction. Hence, MOR/DOR chimeric
      mutant receptors with the MOR TM1 and TM7 sequence (mudelta2mu7S196L) or with the
      MOR TM1 and TM6/7 sequence (mudelta2mu67S196L) were constructed to test such a
      hypothesis. Using four tests of opioid receptor activation, we found that the
      opioid antagonists were full agonists in chimeric mutant receptor if the TM1 and
      TM7 were from different opioid receptors. Additionally, when two of the TM7 amino
      acid residues of MORS196L receptor mutants were mutated (T327A and C330S),
      resulting in a mutant receptor with DOR TM7 sequence, opioid antagonist naloxone
      exhibited full agonistic properties. These data suggest that the efficacy of
      opioid antagonists in the Ser196 mutant can be affected by the interaction
      between TM1 and TM7.

PMID- 15579497
TI  - Vascular calcification mechanisms.
AB  - Vascular calcification is highly correlated with cardiovascular disease
      mortality, especially in patients with ESRD or diabetes. In addition to the
      devastating effects of inappropriate biomineralization seen in cardiac
      valvulopathies, calciphylaxis, and idiopathic arterial calcification, vascular
      calcification is now recognized as a marker of atherosclerotic plaque burden as
      well as a major contributor to loss of arterial compliance and increased pulse
      pressure seen with age, diabetes, and renal insufficiency. In recent years,
      several mechanisms to explain vascular calcification have been identified
      including (1) loss of inhibition, (2) induction of bone formation, (3)
      circulating nucleational complexes, and (4) cell death. Alterations in calcium
      (Ca) and phosphorus (P) balance as seen in patients with ESRD promotes vascular
      calcification via multiple mechanisms and may explain the alarmingly high levels
      of cardiovascular disease deaths in these patients. Strategies to control Ca and
      P levels in patients with ESRD have met with early success in preventing
      progression of vascular calcification. Whether or not vascular calcification can
      be reversed is not yet known, but exciting new studies suggest that this may be
      possible in the future.

PMID- 15579498
TI  - Organ transplantation: halfway through the first century.

PMID- 15579499
TI  - Calcineurin Abeta is central to the expression of the renal type II Na/Pi co
      transporter gene and to the regulation of renal phosphate transport.
AB  - The sensing and response to extracellular phosphate (Pi) concentration is
      preserved from prokaryotes to mammals and ensures an adequate supply of Pi in the
      face of large differences in its availability. In mammals, the kidneys are
      central to Pi homeostasis. Renal Pi reabsorption is mediated by a Na/Pi co
      transporter that is regulated by a renal Pi sensing system and humoral factors.
      The signal transduction by which Pi regulates type II Na/Pi activity is largely
      unknown. It is shown that calcineurin inhibitors specifically and dramatically
      decrease type II Na/Pi gene expression in a proximal tubule cell line and in
      vivo. Mice with genetic deletion of the calcineurin Abeta gene had a marked
      decrease in type II Na/Pi mRNA levels and remarkably did not show the expected
      increase in type II Na/Pi mRNA levels after the challenge of a low-Pi diet. In
      contrast, the regulation of renal 25(OH)-vitamin D 1alpha-hydroxylase gene
      expression by Pi was intact. This is the first demonstration that calcineurin has
      a crucial role in the signal transduction pathway regulating renal Pi homeostasis
      both in vitro and in vivo. These results suggest that the use of calcineurin
      inhibitors contributes to the renal Pi wasting seen in renal transplant patients.

PMID- 15579500
TI  - Human podocytes possess a stretch-sensitive, Ca2+-activated K+ channel: potential
      implications for the control of glomerular filtration.
AB  - Podocytes express many proteins characteristic of smooth muscle, such as actin
      and myosin. They also express receptors to several vasoactive agents, including
      acetylcholine and angiotensin II; these phenotypic properties suggest that
      podocytes are not static entities but may respond to physiologic stimuli. The
      electrophysiologic properties of a conditionally immortalized human podocyte cell
      line that expresses the specific podocyte proteins nephrin, podocin, and
      synaptopodin were examined by patch clamp. Channels that were highly K(+)
      selective and had a conductance of 224 +/- 11.5 pS in symmetrical 150 mM K(+)
      solutions were identified. Channel activity was Ca(2+)- and voltage-dependent,
      being increased with an increase in Ca(2+) or depolarization, and inhibited by
      penitrem A. The conductance and voltage- and Ca(2+)-dependence suggest that this
      is the large-conductance calcium-activated K(+) channel, BK (KCNMA1)-this was
      supported by reverse transcription-PCR experiments that showed the presence of
      the BK encoding mRNA, along with expression of KCNMB subunit types 3 and 4. In
      sections of human glomeruli, immunocytochemistry revealed that BK co-localizes
      with the podocyte-specific protein nephrin, indicating that these channels are
      present in native human podocytes. In whole-cell experiments, penitrem A
      inhibited outward currents to the same extent as tetra-ethyl ammonium (TEA) but
      did not affect the membrane potential. Channel activity was also increased by
      applying suction to the patch pipette or by dilution of the bathing medium,
      indicating that these channels are stretch sensitive. Thus, these channels do not
      contribute to the resting membrane potential but are activated by a rise in
      intracellular Ca(2+), membrane depolarization, cell swelling, or membrane
      stretch. By implication, these results suggest that podocytes may be able to
      respond to changes in the glomerular capillary pressure and modulate the GFR.

PMID- 15579501
TI  - Regulation of the Cl-/HCO3- exchanger AE2 in rat thick ascending limb of Henle's
      loop in response to changes in acid-base and sodium balance.
AB  - The Cl(-)/HCO(3)(-) exchanger AE2 is believed to be involved in transcellular
      bicarbonate reabsorption that occurs in the thick ascending limb of Henle's loop
      (TAL). The purpose of this study was to test whether chronic changes in acid-base
      status and sodium intake regulate AE2 polypeptide abundance in the TAL of the
      rat. Rats were subjected to 6 d of loading with NaCl, NH(4)Cl, NaHCO(3), KCl, or
      KHCO(3). AE2 protein abundance was estimated by semiquantitative immunoblotting
      in renal membrane fractions isolated from the cortex and the outer medulla of
      treated and control rats. In the renal cortex, AE2 abundance was markedly
      increased in response to oral loading with NH(4)Cl or with NaCl. In contrast, AE2
      abundance was unchanged in response to loading with KCl or with NaHCO(3) and was
      decreased by loading with KHCO(3). The response of AE2 in the outer medulla
      differed from that in the cortex in that HCO(3)(-) loading increased AE2
      abundance when administered with Na(+) but had no effect when administered with
      K(+). Immunohistochemistry revealed that NaCl loading increased AE2 abundance in
      the basolateral membrane of both the cortical and the medullary TAL. In contrast,
      NH(4)Cl loading increased AE2 abundance only in the cortical TAL but not in the
      medullary TAL. These results suggest that regulation of the basolateral Cl(
      )/HCO(3)(-) exchanger AE2 plays an important role in the adaptation of
      bicarbonate absorption in the TAL during chronic acid-base disturbances and high
      sodium intake. The present study also emphasizes the contribution of cortical TAL
      adaptation in the renal regulation of acid-base status.

PMID- 15579502
TI  - Indomethacin enhances shuttling of aquaporin-2 despite decreased abundance in rat
      kidney.
AB  - The effect of nonsteroidal antiinflammatory drugs on the regulation of aquaporin
      2 (AQP2) water channels in the kidney was determined. Male Sprague-Dawley rats
      were injected with indomethacin (5 mg/kg twice a day intraperitoneally) for 2 d.
      The control group was injected with vehicle. The expression of AQP2 proteins was
      determined in the kidney by immunoblotting and immunohistochemistry. The
      expression of G(salpha) and type VI adenylyl cyclase was determined by
      immunoblotting. The activity of adenylyl cyclase complexes was determined by
      stimulated accumulation of cAMP. Immunoblotting revealed that indomethacin
      markedly decreased the expression of AQP2. Accordingly, however, the ratio of
      AQP2 expression in the membrane fraction versus that in the cytoplasmic fraction
      was increased. The urinary excretion of AQP2 proteins also increased.
      Immunohistochemistry demonstrated almost exclusive apical labeling of AQP2 with
      scanty cytoplasmic localization along the collecting duct. The expression of
      G(salpha) and adenylyl cyclase VI proteins was decreased. The generation of cAMP
      provoked by arginine vasopressin, sodium fluoride, or forskolin was blunted.
      These results suggest that indomethacin increases the shuttling of AQP2 while it
      decreases its abundance in the collecting duct.

PMID- 15579503
TI  - SRC-family kinase Fyn phosphorylates the cytoplasmic domain of nephrin and
      modulates its interaction with podocin.
AB  - Visceral glomerular epithelial cells (GEC) are critical for normal
      permselectivity of the kidney. Nephrin is a molecule that is expressed
      specifically in GEC in a structure called the slit diaphragm and is required for
      normal morphology and permselectivity of GEC. However, the mechanisms of action
      of nephrin are not understood precisely. The intracellular domain of nephrin has
      six conserved tyrosine residues. It was hypothesized that these tyrosine residues
      are phosphorylated by Src-family kinases and that this phosphorylation modulates
      the function of nephrin. A transient transfection system was used to study the
      role of tyrosine phosphorylation of the cytoplasmic domain of nephrin in its
      function. When nephrin was co-transfected with Src-family kinases Fyn or Src in
      Cos-1 cells, nephrin was strongly tyrosine phosphorylated by Fyn and less so by
      Src. The results with tyrosine-to-phenylalanine mutations suggested that multiple
      tyrosine residues contribute to phosphorylation mediated by Src-family kinases.
      The intracellular domain of nephrin is known to interact with another slit
      diaphragm protein, podocin. When nephrin and podocin were transfected with Fyn,
      the interaction between nephrin and podocin was augmented significantly. Podocin
      was not tyrosine phosphorylated by Fyn; thus, the increased interaction is likely
      to be secondary to tyrosine phosphorylation of nephrin. Fyn also significantly
      augmented the activation of the AP-1 promoter induced by nephrin and podocin. In
      summary, Fyn phosphorylates the cytoplasmic domain of nephrin on tyrosine,
      leading to enhanced association with podocin and downstream signaling of nephrin.

PMID- 15579504
TI  - Role of parathyroid hormone-related protein in the regulation of stretch-induced
      renal vascular smooth muscle cell proliferation.
AB  - In vivo, vascular smooth muscle cells (VSMC) are continuously exposed to
      mechanical cyclic stretch as a result of the pulsatile blood flow from the
      cardiac contractile cycle. Stretch is altered in pathologic conditions and
      contributes to vascular remodeling by modulating VSMC proliferation and death.
      Parathyroid hormone-related protein (PTHrP) is a locally produced poly-protein
      that regulates cell growth. It was shown previously that PTHrP inhibits VSMC
      proliferation through the auto/paracrine pathway by interacting with its
      receptor, the PTH1R, but stimulates VSMC proliferation through the intracrine
      pathway by translocating into the nucleus. In the current study, VSMC that were
      isolated from both resistance and compliance vessels were used to study the role
      of PTHrP in VSMC proliferation under experimental stretch. It is shown that PTHrP
      gene expression is upregulated by stretch and that PTHrP opposes the inhibitory
      effect induced by stretch on VSMC proliferation through the intracrine pathway.
      In addition, it is demonstrated that PTHrP expression is controlled at the post
      transcriptional level by stretch. Taken together, these results strongly suggest
      that PTHrP plays a critical role in the modulation of VSMC proliferation in
      response to stretch. Thus, in conditions in which stretch is increased, such as
      in hypertension or in restenosis after angioplasty, PTHrP may contribute to
      vessel hyperplasia.

PMID- 15579505
TI  - Oxidized LDL induces proliferation and hypertrophy in human umbilical vein
      endothelial cells via regulation of p27Kip1 expression: role of RhoA.
AB  - Oxidized LDL (OxLDL) induces proliferation in human umbilical vein endothelial
      cells (HUVEC). The influence of OxLDL on the cyclin-dependent kinase inhibitor
      p27(Kip1), on the activity of the small GTPase RhoA as a known regulator of
      p27(Kip1), and on resulting cell proliferation and hypertrophy was studied. HUVEC
      were stimulated with OxLDL (1 to 50 mug/ml). Proliferation was quantified by (3)H
      thymidine incorporation, colorimetric 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2h
      tetrazolium bromide assay, and cell count and was compared with proliferation of
      HUVEC that were transfected with dominant negative RhoA or treated with the Rho
      kinase inhibitor Y27632. Hypertrophy was quantified by (3)H-leucine incorporation
      and by planimetry. p27(Kip1) expression was determined by Western blot analysis.
      p27(Kip1) was downregulated by transient transfection with antisense
      oligonucleotides. Low concentrations of OxLDL induced proliferation of HUVEC,
      paralleled by a persistent decrease of p27(Kip1) expression. With the use of
      antisense oligonucleotides, further downregulation of p27(Kip1) expression
      enhanced the OxLDL-induced proliferative response. High concentrations of OxLDL
      resulted in cellular hypertrophy and caused a delayed increase in p27(Kip1)
      expression after initial downregulation. Concomitant, OxLDL caused a significant
      activation of the small GTPase RhoA. In cells that were transfected with dominant
      negative RhoA, the effect of OxLDL on p27(Kip1) expression and on cellular
      proliferation was abolished. HUVEC that were preincubated with the Rho-kinase
      inhibitor Y27632 also showed a significantly decreased proliferative response to
      OxLDL stimulation. In summary, OxLDL has a dual effect on cell-cycle progression
      via regulation of p27(Kip1) expression, resulting in cellular proliferation and
      hypertrophy, involving activation of RhoA. OxLDL may importantly contribute to
      vascular hyperplasia in atherosclerosis and other diseases associated with
      increased levels of OxLDL.

PMID- 15579506
TI  - A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo.
AB  - Gene targeting has been used to create a variety of lines of mice with Pkd1
      mutations that share many common features. Homozygous Pkd1 mutants invariably
      develop pancreatic and renal cysts if they survive to day 15.5 post coitum and
      die in either the fetal or the perinatal period. In contrast, mice with
      heterozygous mutations of Pkd1 are generally normal and have few if any renal
      cysts. These features have limited the utility of these models as tools to study
      the pathogenesis of cyst formation and the effect of various therapeutic
      interventions on disease progression. This report describes a new line of mice
      with a floxed allele of Pkd1 (Pkd1(cond)) that has an FRT-flanked neomycin
      cassette inserted into intron 1 and lox P sites inserted into intron 1 and intron
      4. The Pkd1(cond) allele is fully functional, and homozygotes are viable and
      healthy. It is shown that the lox P and FRT sites can be selectively induced to
      recombine to produce two new alleles, Pkd1(del2-4) and Pkd1(cond-Deltaneo), by
      crossing to animals that express either the cre or FLPe recombinase,
      respectively. It is found that Pkd1(del2-4) allele functions as a true null,
      whereas presence or absence of the neomycin gene has no functional effects. It
      also is shown that somatic loss of Pkd1 results in renal and hepatic cysts. This
      new line of mice will be invaluable in the study of Pkd1 biology and serve as a
      powerful new tool that can be used to study the pathogenesis of autosomal
      dominant polycystic kidney disease.

PMID- 15579507
TI  - The major podocyte protein nephrin is transcriptionally activated by the Wilms'
      tumor suppressor WT1.
AB  - NPHS1 encodes the structural protein nephrin, which has a crucial role in the
      filtration barrier of the glomerular podocyte. Mutations or deregulation of NPHS1
      are associated with a variety of renal diseases, including the Finnish type
      congenital nephrotic syndrome. This study analyzed a potential regulation of
      nephrin by the Wilms' tumor protein, Wt1. Using an inducible U2OS osteosarcoma
      cell line, it is shown that upon Wt1 induction, endogenous nephrin mRNA becomes
      highly upregulated. Co-transfection studies demonstrate that Wt1 can activate the
      nephrin promoter >10-fold. DNase footprinting and mutation analysis identify a
      Wt1 responsive element in the nephrin promoter, which is required for the binding
      of Wt1 protein. Mutations or deletion of this Wt1 responsive element completely
      abolished transactivation of the nephrin promoter by Wt1. Moreover, transgenic
      analysis demonstrates the requirement of the identified binding site to direct
      podocyte-specific expression of a reporter gene in transgenic mice, thus
      confirming the importance of this site for the regulation of nephrin in vivo.
      Finally, it is shown that nephrin expression is lowest in kidneys of mice that
      lack specifically the Wt1(-KTS) splice variant, but in comparison with wild-type
      littermates, it is also reduced in animals with disruption of the Wt1(+KTS)
      splice variant. Taken together, these data identify nephrin as a direct
      transcriptional target for Wt1 and underline the importance of Wt1 as a key
      regulator in podocyte function.

PMID- 15579508
TI  - Modulation of proliferating renal epithelial cell affinity for calcium oxalate
      monohydrate crystals.
AB  - Adhesion of urinary crystals to distal tubular cells could be a critical event
      that triggers a cascade of responses ending in kidney stone formation. Monolayer
      cultures of distal nephron-derived MDCKI cells were used as a model to study
      crystal-cell interactions. COM crystal adhesion reached a peak 2 d after plating
      and progressively fell thereafter. The decline in crystal binding was accelerated
      by prostaglandin E(2) (PGE(2)) supplementation and delayed by blockade of PG
      production. Crystals avidly adhered to cells that migrated in to repair a scrape
      wound made in the monolayer and after a transient hypoglycemic insult. Exposure
      of MDCKI cells to uric acid crystals and soluble uric acid was also associated
      with increased crystal adhesion. Treatment of physically or hypoglycemically
      injured cells with trypsin or neuraminidase reduced crystal binding to baseline
      levels, suggesting that increased exposure of cell surface glycoproteins mediated
      the effect, whereas PGE(2) treatment blunted crystal binding to regenerating
      cells. Furthermore, when cells were grown in the presence of synthetic d
      mannosamine analogues that can modify the conformation of cell surface
      sialoglycoconjugates, crystal binding to proliferating cells was decreased,
      whereas blockade of N-glycosylation with tunicamycin increased crystal adhesion
      to these cells. Therefore, COM crystal binding is enhanced to growing renal
      cells, synthesis of N-glycosylated cell surface proteins is essential to
      downregulate crystal binding to cells, and this response is modulated by
      physiologic signals such as PGE(2). Sialic acid residues seem to mediate crystal
      adhesion to growing cells, either directly or via linkage to other crystal
      binding molecules. Subtle renal injury and subsequent nephron repair could be a
      factor promoting crystal adhesion and favoring calculus formation.

PMID- 15579509
TI  - Reversal of glomerular lesions involves coordinated restructuring of glomerular
      microvasculature.
AB  - There is increasing evidence from both human and experimental studies that at
      least partial reversal of glomerulosclerosis can be achieved by glomerular
      remodeling. This requires substantial changes in glomerular architecture,
      specifically of glomerular capillaries. It was the purpose of the present study
      to characterize the stereologic and topologic characteristics of glomerular
      capillaries when partial reversal of glomerular lesions is achieved by high-dose
      angiotensin-converting enzyme inhibitor treatment. Sham-operated male Sprague
      Dawley rats were compared with subtotally nephrectomized (SNX) rats. The latter
      were kept untreated for 8 wk and subsequently randomly divided into one group
      that was continued without treatment and another group that was treated with
      enalapril (48 mg/kg body wt per d administered in the drinking fluid for 4 wk).
      Renal morphology was evaluated after 8 or 12 wk, respectively, by stereologic
      techniques after pressure-controlled perfusion fixation. In SNX rats at 8 and
      particularly at 12 wk, the glomerulosclerosis index was significantly higher than
      in sham-operated rats. At 12 wk, it was lower in rats that had been treated for 4
      wk with enalapril compared with untreated SNX rats, suggesting partial reversal
      of glomerular lesions. This was associated with a decrease in mean glomerular
      volume and mean glomerular tuft volume, a reduced number of capillaries per
      glomerulus, and reduced total length of capillaries per glomerulus but without
      any significant change in the length of individual capillaries. The numerical
      capillary density (Euler number density) as an index of topologic complexity did
      not change. The total capillary surface area per glomerulus was strikingly
      increased after subtotal nephrectomy and partially reversed after enalapril. This
      was accounted for primarily by fewer capillaries without any change in diameter.
      In parallel, the number of endothelial cells per glomerulus was strikingly
      increased after subtotal nephrectomy and decreased with enalapril treatment, but
      endothelial cell volume remained elevated. The study shows harmonious coordinate
      remodeling of the entire glomerulus during regression of glomerular lesions after
      subtotal nephrectomy. Proportionate reduction of glomerular volume and capillary
      number without change of individual capillary length were found. The numerical
      capillary density of the tuft therefore remained unchanged.

PMID- 15579510
TI  - Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated
      lipocalin.
AB  - Acute renal failure secondary to ischemic injury remains a common problem, with
      limited and unsatisfactory therapeutic options. Neutrophil gelatinase-associated
      lipocalin (NGAL) was recently shown to be one of the maximally induced genes
      early in the postischemic kidney. In this study, the role of NGAL in ischemic
      renal injury was explored. Intravenous administration of purified recombinant
      NGAL in mice resulted in a rapid uptake of the protein predominantly by proximal
      tubule cells. In an established murine model of renal ischemia-reperfusion
      injury, intravenous NGAL administered before, during, or after ischemia resulted
      in marked amelioration of the morphologic and functional consequences, as
      evidenced by a significant decrease in the histopathologic damage to tubules and
      in serum creatinine measurements. NGAL-treated animals also displayed a reduction
      in the number of apoptotic tubule cells and an increase in proliferating proximal
      tubule cells after ischemic injury. The results indicate that NGAL may represent
      a novel therapeutic intervention in ischemic acute renal failure, based at least
      in part on its ability to tilt the balance of tubule cell fate toward survival.

PMID- 15579511
TI  - Expression and function of Ets-1 during experimental acute renal failure in rats.
AB  - The Ets family of transcription factors is defined by a conserved DNA-binding Ets
      domain that forms a winged helix-turn-helix structure motif. The Ets family is
      involved in a diverse array of biologic functions, including cellular growth,
      migration, and differentiation. The hypothesis in this study was that Ets-1 is re
      expressed during regeneration after acute renal failure (ARF) and plays a key
      role in the transcriptional regulation of cyclin D1 and the cell cycle
      progression in renal tubular cells. For clarifying the significance of Ets-1 in
      ARF, a rat ARF model in vivo and LLC-PK1 cells as an in vitro model were used.
      After the left rat renal artery was clamped for 1 h, the whole kidney homogenate
      was examined and total RNA was extracted at 6, 12, 24, 48, and 72 h after
      reperfusion by Western blot analysis and real-time reverse transcription-PCR. Ets
      1 mRNA and protein expression were strongly increased at 6 to 24 h after the
      ischemia, respectively. The expression of hypoxia-inducible factor-1alpha was
      increased dramatically as early as 6 h after ischemia-reperfusion and decreased
      at 48 and 72 h after ischemia-reperfusion. In the immunohistologic examination,
      Ets-1 was expressed in the proximal tubules and coexpressed with proliferating
      cell nuclear antigen (PCNA). Furthermore, overexpression of Ets-1 promoted the
      cell cycle and increased the promoter activity and protein expression of cyclin
      D1 in LLC-PK1 cells. Ets-1 promoter activity increased between 3 and 6 h in
      hypoxia, and hypoxia also induced changes in the Ets-1 protein level in LLC-PK1
      cells. The Ets-1 induction by hypoxia was abolished by the transfection of
      dominant-negative hypoxia-inducible factor-1alpha. A gel shift assay demonstrated
      that Ets-1 binds to the ets-1 binding site of the cyclin D1 promoter in the
      ischemia-reperfusion condition. Overexpression of Ets-1 did not significantly
      change the caspase 3 activity or the value of cell death ELISA in LLC-PK1 cells.
      Taken together, these data suggest that Ets-1 plays a key role in the cell-cycle
      progression of renal tubules in ARF. The Ets-1 pathway may regulate the
      transcription of cyclin D1 and control the regeneration of renal tubules in ARF.

PMID- 15579512
TI  - Acute renal failure in endotoxemia is dependent on caspase activation.
AB  - In previous work, it was demonstrated that apoptosis occurs in the kidney during
      LPS-induced acute renal failure (ARF). However, the relative importance of
      apoptosis in LPS-induced ARF remained unproven. Because the caspase enzyme
      cascade is responsible for carrying out apoptosis, it was hypothesized that
      treatment with a caspase inhibitor would protect mice from LPS-induced ARF.
      C57BL/6 mice received an injection of LPS and were treated with either the broad
      spectrum caspase inhibitor z-VAD-fmk or vehicle and compared with unmanipulated
      mice. LPS induced a significant increase in caspase-3 activity in vehicle-treated
      mice, which was significantly inhibited by z-VAD. Mice that were treated with z
      VAD were protected from ARF and demonstrated significantly less apoptosis as
      measured by both terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling staining and DNA laddering. Although apoptosis is classically described
      as a noninflammatory process, z-VAD treatment significantly attenuated multiple
      markers of inflammation, such as renal neutrophil infiltration and renal
      expression of the neutrophil chemotactic factor macrophage inflammatory protein
      2. Thus, caspase inhibition may protect against LPS-induced ARF not only by
      preventing apoptotic cell death but also by inhibiting inflammation. These data
      raise the possibility that apoptotic kidney cells may actually be a source of
      this local inflammation, contributing to subsequent nonapoptotic renal injury.

PMID- 15579513
TI  - Myocardial infarction enhances progressive renal damage in an experimental model
      for cardio-renal interaction.
AB  - Studied were the effects of myocardial infarction (MI) on mild renal function
      loss in unilateral nephrectomized (UnX) rats. UnX was performed, followed after 1
      wk by a variable MI (UnX + MI; n = 24). Rats with only UnX (n = 15) or MI (n = 9)
      and double sham animals (CON, n = 15) served as controls. Renal outcome was
      measured by proteinuria and plasma creatinine. Focal glomerulosclerosis (FGS)
      incidence was evaluated by renal histology. Cardiac function and systolic BP were
      measured. A division into small and large infarcts after UnX was made a priori,
      resulting in two groups, one with a mild MI (<20%; n = 15) and one with a
      moderate MI (>20%; n = 9). Mild proteinuria up to 55.5 mg/d was observed in the
      UnX + mild MI group, whereas proteinuria rose significantly higher to 124.5 mg/d
      in the UnX + moderate MI group. Incidence of FGS was significantly increased in
      both UnX + MI groups compared with all other groups. The average MI size was 18%,
      17%, and 25% in the MI, UnX + mild MI, and UnX + moderate MI group, respectively.
      LVP in both UnX + MI groups was correlated with proteinuria, indicative of a
      cardio-renal interaction. Clinically, these data imply that more patients are at
      risk for cardiovascular events and that after such an event, their chance of more
      renal function loss increases. Finding the underlying mechanism will enable
      improved protection for both kidneys and heart.

PMID- 15579514
TI  - Acute peritoneal dialysis in rats results in a marked reduction of interstitial
      colloid osmotic pressure.
AB  - The aim of this study was to investigate whether the interstitial colloid osmotic
      pressure (COP(i)) of peritoneum is of importance for peritoneal fluid
      reabsorption during peritoneal dialysis (PD). For testing this hypothesis, a
      method to isolate interstitial fluid from the peritoneal membrane and to measure
      the interstitial COP(i) in the normal peritoneum and directly after the
      initiation of PD needed to be developed and validated. Eighteen female rats were
      anesthetized subcutaneously in the neck region with fentanyl-midazolam (1:1).
      Nylon wicks were implanted postmortem by means of a plastic catheter in the
      tissue just underneath the peritoneal surface. The characteristics of this fluid
      were compared with that isolated from wicks that were implanted in intermuscular
      spaces in hindlimb muscle and back subcutis. All wicks were removed after 20 min
      and centrifuged. The wick fluid was collected and analyzed in a colloid osmometer
      constructed for submicroliter samples, and interstitial fluid COP was compared
      with that of plasma. PD was initiated by injecting 20 ml of 3.86% glucose
      containing PD fluid (Dianeal) into the peritoneal cavity, over a dwell time of 4
      h. Control rats received no PD. The ratio of COP(i) to that of plasma (COP(p))
      during control was 0.65 +/- 0.05 in peritoneum, 0.53 +/- 0.04 in muscle, and 0.59
      +/- 0.05 in skin. After a PD dwell, the ratio was 0.29 +/- 0.03 in peritoneum,
      0.54 +/- 0.08 in muscle, and 0.41 +/- 0.06 in skin. Thus, the COP ratio in
      peritoneum fell by 55% (P = 0.014) and in skin by 30% (P = 0.03), whereas the COP
      ratio in muscle was unchanged. The results suggest that acute PD results in a
      marked fall of the COP(i) in the peritoneal membrane, shifting the Starling
      equilibrium toward an absorptive state. The effect was restricted to the
      peritoneal membrane and, to some extent, the skin. It is speculated that the
      increase in peritoneal hydrostatic pressure after PD causes an increase in
      interstitial tissue volume, with primarily a dilution of interstitial colloids.

PMID- 15579515
TI  - Continuum of renoprotection with losartan at all stages of type 2 diabetic
      nephropathy: a post hoc analysis of the RENAAL trial results.
AB  - Renin angiotensin system inhibitor therapy is seldom offered to individuals who
      have diabetes and advanced chronic kidney disease because of safety concerns. In
      this post hoc, secondary analysis of the Reduction of Endpoints in NIDDM with the
      Angiotensin II Antagonist Losartan (RENAAL) trial, angiotensin antagonism
      risk/benefit profile was assessed in 1513 individuals with type 2 diabetes and
      overt nephropathy. Incidence of ESRD, hospitalizations for heart failure,
      withdrawals for adverse events, and proteinuria during losartan or conventional
      treatment were compared within three tertiles of baseline serum creatinine
      concentration (highest, 2.1 to 3.6 mg/dl; middle, 1.6 to 2.0 mg/dl; lowest, 0.9
      to 1.6 mg/dl). Losartan decreased the risk of ESRD by 24.6, 26.3, and 35.3% in
      highest, middle, and lowest tertiles, respectively. For every 100 patients with
      serum creatinine >2.0, 1.6 to 2.0, or <1.6 mg/dl, respectively, 4 yr of losartan
      therapy was estimated to save 18.9, 8.4, and 2.9 ESRD events and US$1,502,855,
      US$1,021,770, and US$528,591 costs for renal replacement therapy. Losartan also
      decreased the hospitalizations for heart failure by 50.2 and 45.1, in the highest
      and middle tertile, respectively. Withdrawals for adverse events other than heart
      failure were comparable between tertiles and treatment groups. Proteinuria
      decreased more on losartan than on placebo in all tertiles (highest, 24 versus 
      8%; middle, 16 versus -8%; lowest, 15 versus -10%). In proteinuric individuals
      with type 2 diabetes, losartan therapy reduced ESRD and hospitalizations for
      heart failure and was well tolerated at all levels of renal function. Angiotensin
      II antagonism is a suitable and well-tolerated treatment for individuals with
      type 2 diabetes even with GFR levels approaching renal replacement therapy.

PMID- 15579516
TI  - Pharmacologic demonstration of the synergistic effects of a combination of the
      renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the
      angiotensin II-renin feedback interruption.
AB  - Interrupting the renin-angiotensin system (RAS) with a usual daily dose of a
      single-site RAS inhibitor does not achieve complete and long-lasting
      pharmacologic blockade. Hormonal and BP effects were compared for 48 h after
      administration of single oral doses of 300 mg (high dose) of the renin inhibitor
      aliskiren (A300) and 160 mg (standard antihypertensive dose) of the AT1 receptor
      antagonist valsartan (V160) and their combination each at half dose (A150+V80) in
      12 mildly sodium-depleted normotensive individuals. In this double-blind, placebo
      controlled, randomized, four-period crossover study, A300 decreased plasma renin
      activity and angiotensin I and II levels for 48 h, stimulated immunoreactive
      active renin release more strongly than V160, and decreased urinary aldosterone
      excretion for a longer duration than V160. In contrast to V160, the A150+V80
      combination did not increase plasma angiotensins. The renin and aldosterone
      effects of the A150+V80 combination were similar to those of A300 and greater
      than those of V160. When plasma drug concentrations were taken into account, the
      A150 +V80 combination had a synergistic effect on renin release. The A150+V80
      combination lowered BP at least as effectively as either higher dose monotherapy.
      In conclusion, in mildly sodium-depleted normotensive individuals, the long
      lasting effects of aliskiren alone or in combination with valsartan on plasma
      immunoreactive active renin and urinary aldosterone effects demonstrate strong
      and prolonged blockade of angiotensin II at the kidney and the adrenal level.
      Moreover, a renin inhibitor and AT1R antagonist combination may provide
      synergistic effects on RAS hormone levels.

PMID- 15579517
TI  - Resting energy expenditure and subsequent mortality risk in peritoneal dialysis
      patients.
AB  - Cardiovascular disease is the leading cause of death in ESRD patients and is
      strongly associated with malnutrition. The mechanism of malnutrition is not
      clear, but hypermetabolism is suggested to contribute to cardiac cachexia. This
      study examined resting energy expenditure (REE) in relation to the clinical
      outcomes of ESRD patients who receive continuous ambulatory peritoneal dialysis
      (CAPD) treatment. A prospective observational cohort study was performed in 251
      CAPD patients. REE was measured at study baseline using indirect calorimetry
      together with other clinical, nutritional, and dialysis parameters. Patients were
      followed up for a mean +/- SD duration of 28.7 +/- 14.3 mo. REE was 39.1 +/- 9.6
      and 40.1 +/- 9.0 kcal/kg fat-free edema-free body mass per day for men and women,
      respectively (P = 0.391). Using multiple regression analysis, fat-free edema-free
      body mass-adjusted REE was negatively associated with residual GFR (P < 0.001)
      and serum albumin (P = 0.046) and positively associated with diabetes (P =
      0.002), cardiovascular disease (P = 0.009), and C-reactive protein (P = 0.009).
      At 2 yr, the overall survival was 63.3, 73.6, and 95.9% (P < 0.0001), and
      cardiovascular event-free survival was 72.3, 84.6, and 97.2% (P = 0.0003),
      respectively, for patients in the upper, middle, and lower tertiles of REE.
      Adjusting for age, gender, diabetes, and cardiovascular disease, patients in the
      upper and middle tertiles showed a 4.19-fold (95% confidence interval, 2.15 to
      8.16; P < 0.001) and a 2.90-fold (95% confidence interval, 1.49, 5.63; P = 0.002)
      respective increase in the risk of all-cause mortality compared with those in the
      lower tertile. However, the significance of REE in predicting mortality was
      gradually reduced when additional adjustment was made for C-reactive protein,
      serum albumin, and residual GFR in a stepwise manner. In conclusion, a higher REE
      is associated with increased mortality and cardiovascular death in CAPD patients
      and is partly related to its close correlations with residual kidney function,
      cardiovascular disease, inflammation, and malnutrition in these patients.

PMID- 15579518
TI  - Frequency of sit-down patient care rounds, attainment of clinical performance
      targets, hospitalization, and mortality in hemodialysis patients.
AB  - Sit-down patient rounding in hemodialysis units allows providers to focus
      collectively on each patient's needs and may affect patient outcomes positively.
      The objective was to examine whether sit-down rounding practices improve patient
      outcomes in a cohort of 644 adult hemodialysis patients from 75 outpatient
      dialysis clinics in 17 states throughout the United States who survived at least
      6 mo after enrollment (average follow-up, 3.2 yr). Achievement of well-accepted 6
      mo clinical performance targets of albumin (> or =3.5 g/dl), hemoglobin (> or =11
      g/dl), calcium-phosphate product (<60 mg(2)/dl(2)), dose (Kt/V > or =1.2), and
      vascular access type (fistula); hospitalization rates; and all-cause mortality
      served as outcomes. Monthly or more frequent sit-down rounds were conducted in 36
      (48%) of 75 clinics, representing 287 (45%) of 644 patients. More frequent sit
      down rounds were positively associated with an increased chance of achieving the
      6-mo clinical performance target for albumin compared with less frequent rounds
      (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.12 to 3.15); patients who
      were treated at clinics with more frequent rounds also had nearly twice the odds
      of achieving more of the five performance targets (OR, 1.95; 95% CI, 1.11 to
      3.42). After adjustment for potential confounders, patients who were treated at
      clinics with more frequent sit-down rounds were 32% less likely to be
      hospitalized (incidence rate ratio, 0.68; 95% CI, 0.51 to 0.91), had fewer
      hospital days per year (rate ratio, 0.50; 95% CI, 0.26 to 0.98), and were 29%
      less likely to die (relative hazard, 0.71; 95% CI, 0.53 to 0.95). Adjustment for
      some clinical performance targets attenuated the statistical significance of the
      association with hospitalization. More frequent sit-down rounds in hemodialysis
      units are associated with better patient outcomes, including an increased chance
      of meeting the albumin clinical performance target, decreased hospitalization,
      and decreased risk of mortality. This association may be due to the positive
      effect of collaborative discussion by the patient care team of short- and long
      term care goals for individual patients.

PMID- 15579519
TI  - Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of
      randomized, controlled trials.
AB  - Anemia affects almost all patients with chronic kidney disease (CKD), reduces
      quality of life, and is a risk factor for early death. Higher hemoglobin (Hb)
      targets have been widely advocated because of data from observational studies
      showing that higher Hb is associated with improved survival and quality of life,
      but higher Hb targets may cause access thrombosis and hypertension and are
      costly. This study aimed to evaluate the benefits and harms of different Hb
      targets in CKD on the basis of randomized trial evidence. A comprehensive search
      of the Cochrane Trials Registry, Medline, Embase, and reference lists was
      performed. Two independent reviewers assessed studies for inclusion criteria and
      extracted data on all-cause mortality, cardiovascular disease, strokes,
      hypertension, seizures, hyperkalemia, access thrombosis, and quality of life.
      Analysis was by a random-effects model, and results are expressed as relative
      risk (RR) or weighted mean difference with 95% confidence intervals (CI).
      Nineteen relevant trials were identified. Twelve trials (638 patients) compared
      use of erythropoietin versus no erythropoietin treatment, and seven trials (2058
      patients) compared higher versus lower Hb targets. Compared with Hb values of
      >130 g/L or more in the CKD population with cardiovascular disease, Hb values of
      <120 g/L were associated with lower all-cause mortality (RR, 0.84; 95% CI, 0.71
      to 1.00). Hb values of 100 g/L or less reduced the risk of hypertension (RR,
      0.50; 95% CI, 0.33 to 0.76) but increased the risk of seizures (RR, 5.25; 95% CI,
      1.13 to 24.34). From the available trial evidence, in CKD patients with
      cardiovascular disease, the benefits associated with higher Hb targets (reduced
      seizures) are outweighed by the harms (increased risk of hypertension and death).
      There is insufficient data to guide decisions in patients without cardiovascular
      disease or in the predialysis population.

PMID- 15579520
TI  - Impact of diabetes and hepatitis after kidney transplantation on patients who are
      affected by hepatitis C virus.
AB  - Complications associated with use of donor hepatitis C-positive kidneys (DHCV+)
      have been attributed primarily to posttransplantation liver disease (as a result
      of hepatitis C disease). The role of posttransplantation diabetes has not been
      explored in this setting. With the use of the United States Renal Data System
      database, 28,942 Medicare KT recipients were studied from January 1, 1996,
      through July 31, 2000. Cox proportional hazards regression models were used to
      calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV
      (D+/R-, D+/R+, D-/R+ and D-/R-) with Medicare claims for de novo
      posttransplantation HCV and posttransplantation diabetes. The peak risk for
      posttransplantation HCV was in the first 6 mo after transplantation. The
      incidence of posttransplantation HCV after transplantation was 9.1% in D+/R-,
      6.3% in D+/R+, 2.4% in D-/R+, and 0.2% in D-/R-. The incidence of
      posttransplantation diabetes after transplantation also peaked early and was
      43.8% in D+/R-, 46.6% in D+/R+, 32.3% in D-/R+, and 25.4% in D-/R-. Associations
      for both complications were significant in adjusted analysis (Cox regression).
      Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61)
      and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to
      2.11) were independently associated with an increased risk of death, but
      posttransplantation diabetes accounted for more years of life lost, particularly
      among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute
      substantially to the increased risk of death associated with use of DHCV+ kidneys
      and accounts for more years of life lost than posttransplantation HCV. Because
      HCV infection acquired after transplantation is so difficult to treat, methods
      that have been shown to reduce viral transmission warrant renewed attention.

PMID- 15579521
TI  - A comparison of iothalamate-GFR and serum creatinine-based outcomes: acceleration
      in the rate of GFR decline in the African American Study of Kidney Disease and
      Hypertension.
AB  - In renal clinical trials, both slope-based and time-to-event renal outcomes have
      been used. These outcomes are typically based on estimates of GFR obtained using
      creatinine or iothalamate GFR (iGFR). The African American Study of Kidney
      Disease and Hypertension (AASK) was a trial in 1094 African Americans with
      hypertensive nephrosclerosis, which examined the effects of two levels of BP
      control and three antihypertensive regimens. This study compared the effects of
      the AASK interventions on outcomes based on serum creatinine with corresponding
      outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine
      measurements. The iGFR-based outcomes included (1) a time-to-event composite
      outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome
      including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo
      after randomization (acute slope); (4) mean decline in GFR starting 3 mo after
      randomization (chronic slope); and (5) mean decline in GFR from baseline (total
      slope). The corresponding creatinine-based outcomes were (1) a composite of
      doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of
      serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean
      change in estimated GFR (eGFR), where eGFR was estimated from a regression
      equation for GFR depending primarily on serum creatinine and developed in AASK
      enrollees. Mean changes in iGFR and eGFR were also compared under extended models
      that allowed for the possibility that the rate of GFR decline may change over
      time during the chronic phase. an apparent acceleration in rate of decline of
      renal function over time was found. Subtle differences were observed between
      effects of the interventions on some of the creatinine and iGFR slope-based
      outcomes, but the main conclusions of the trial were similar for the serum
      creatinine and iothalamate-based measurements. This has important implications
      for the design of clinical trials with renal outcomes.

PMID- 15579522
TI  - Inflammatory and prothrombotic markers and the progression of renal disease in
      elderly individuals.
AB  - Inflammatory and prothrombotic markers are elevated in individuals with mild to
      moderate renal disease. It was hypothesized that these markers may also be
      determinants of the progression of renal disease. The association of six markers
      serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor
      VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline
      in estimated GFR in the Cardiovascular Health Study, a community-based cohort of
      elderly individuals, was analyzed. Linear regression was used to determine
      predictors of an annualized change in serum creatinine as the main outcome.
      Duration of follow-up was 7 yr for the original cohort and 4 yr for the more
      recently recruited black cohort. A total of 588 (12.7%) individuals had a decline
      in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P <
      0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001)
      levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were
      associated with a rise in creatinine, after adjusting for age. With additional
      adjustments for race, gender, baseline creatinine, systolic and diastolic BP,
      lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen,
      WBC count, and lower albumin and hemoglobin levels remained associated with a
      rise in creatinine. Similar results were found for decline in estimated GFR. The
      decline in GFR was greater with increasing number of inflammatory or
      prothrombotic markers that were above the median (below for hemoglobin and
      albumin). Inflammatory and prothrombotic markers are predictors for a change in
      kidney function in elderly individuals. Interventions that reduce inflammation
      might confer significant cardiovascular and renal benefits.

PMID- 15579523
TI  - Safety and efficacy of low molecular weight heparins for hemodialysis in patients
      with end-stage renal failure: a meta-analysis of randomized trials.
AB  - Low molecular weight heparins (LWMH) are the preferred initial treatment for many
      thromboembolic disorders but are renally excreted and relatively contraindicated
      in patients with renal failure because of concerns of increased bleeding risks.
      The purpose of this study was to evaluate the safety and efficacy of LMWH
      compared with unfractionated heparin (UFH) for preventing thrombosis of the
      extracorporeal dialysis circuit. Studies were identified with the use of MEDLINE,
      EMBASE, Cochrane Central Register of Controlled Trials, and FirstSearch;
      reference lists were reviewed; and pharmaceutical companies were contacted.
      Randomized, controlled trials that compared an LMWH with another anticoagulant
      during hemodialysis in patients with ESRD and reported at least one of bleeding,
      extracorporeal circuit thrombosis, or anti-Xa levels were chosen. Two reviewers
      independently extracted data on methodologic quality, study design, clinical
      outcomes, and anti-Xa levels. Seventeen trials were included in this systematic
      review, 11 of which were included in the meta-analysis. It was found that LMWH
      did not significantly affect the number of bleeding events (relative risk, 0.96;
      95% confidence interval [CI], 0.27 to 3.43), bleeding assessed by vascular access
      compression time (weighted mean difference, -0.87; 95% CI, -2.75 to 1.02), or
      extracorporeal circuit thrombosis (relative risk, 1.15; 95% CI, 0.70 to 1.91) as
      compared with UFH. LMWH seem to be as safe as UFH in terms of bleeding
      complications and as effective as UFH in preventing extracorporeal circuit
      thrombosis. However, inferences from these trials assessing anticoagulation for
      patients who undergo hemodialysis will continue to be weak until larger, more
      rigorous randomized trials are conducted.

PMID- 15579524
TI  - Short bacterial DNA fragments: detection in dialysate and induction of cytokines.
AB  - A number of bacterial cytokine-inducing substances (CIS) such as
      lipopolysaccharides (LPS) and exotoxins have been detected in dialysate and may
      contribute to inflammation in hemodialysis patients. Short DNA fragments,
      oligodeoxynucleotides (ODN) of 6 to 20 nucleotides, are able to bind to Toll-like
      receptors and are stimulatory on immune cells. ODN induce natural killer cell
      activity and induce IFN-gamma, TNF-alpha, and IL-6 from mononuclear cells. The
      presence of ODN in dialysate samples and bacterial cultures was investigated. ODN
      were extracted from fluids by adsorption to reverse-phase columns. ODN were
      detected in 18 of 20 investigated dialysate samples, in eight of 10 reverse
      osmosis water samples, and in all cultures from various bacterial strains. The
      presence of bacterial DNA in dialysate was confirmed by PCR specific for
      bacterial tRNA gene sequences. Saline for intravenous use contained 0.02 +/- 0.01
      microg/ml DNA, dialysate samples contained 0.28 +/- 0.02 microg/ml, and
      Pseudomonas cultures contained 1.0 +/- 0.03 microg/ml DNA. ODN from bacterial
      cultures were only partially removed by ultrafiltration and were able to diffuse
      through regular high-flux dialyzer membranes. Synthetic cytosine-guanosine
      dinucleotide-containing ODN were able to induce IL-6 in human mononuclear cells.
      It is concluded that short bacterial-derived DNA fragments are present in
      clinically used fluids, e.g., dialysate. These fragments are of sufficient small
      size to pass through dialyzer membranes. Bacterial DNA fragments may be an
      overlooked factor contributing to inflammation in hemodialysis patients.

PMID- 15579525
TI  - The critical role of SRC homology domain 2-containing tyrosine phosphatase-1 in
      recombinant human erythropoietin hyporesponsive anemia in chronic hemodialysis
      patients.
AB  - The molecular mechanism of anemia that is hyporesponsive to recombinant human
      erythropoietin (rHuEPO) in hemodialysis patients without underlying causative
      factors has not been investigated fully in hematopoietic stem cell system.
      Circulating CD34+ cells (1 x 10(4)) were isolated from rHuEPO hyporesponsive
      hemodialysis patients (EPO-H; n = 9), patients who were responsive to rHuEPO (EPO
      R; n = 9), and healthy control subjects (n = 9). The patients with known causes
      of EPO hyporesponsiveness were eliminated from the current study. The cells were
      cultured in STEM PRO 34 liquid medium, supplemented with rHuEPO, IL-3, stem cell
      factor, and granulocyte-macrophage colony stimulating factor for 7 d and then
      transferred to a semisolid methylcellulose culture medium for performing burst
      forming unit-erythroid (BFU-E) colony assay. Expression of src homology domain 2
      (SH2)-containing tyrosine phosphatase-1 (SHP-1), phosphorylated Janus kinase 2 (p
      JAK2), and phosphorylated signal transducer and activator of transcription 5 (p
      STAT5) was assessed with Western blot analysis. In EPO-H patients, SHP-1
      antisense or scrambled S-oligos were included in the culture medium, and its
      effects were evaluated. The number of circulating CD34+ cells was not
      statistically different among the three groups, and their proliferation rates
      were similar for 7 d in culture. However, BFU-E colonies were significantly
      decreased in EPO-H patients compared with EPO-R and control groups. The mRNA and
      protein expression of SHP-1 and p-SHP-1 was significantly increased, whereas that
      of p-STAT5 was reduced in EPO-H patients. The inclusion of SHP-1 antisense S
      oligo in culture suppressed SHP-1 protein expression associated with p-STAT5
      upregulation, increase in p-STAT5-regulated genes, and partial recovery of BFU-E
      colonies. In EPO-H hemodialysis patients, the EPO signaling pathway is attenuated
      as a result of dephosphorylation of STAT5 via upregulation of SHP-1 phosphatase
      activity, and SHP-1 may be a novel target molecule to sensitize EPO action in
      these patients.

PMID- 15579526
TI  - Dietary factors and the risk of incident kidney stones in men: new insights after
      14 years of follow-up.
AB  - Diet plays an important role in the pathogenesis of kidney stones. Because the
      metabolism of many dietary factors, such as calcium, may change with age, the
      relation between diet and kidney stones may be different in older adults.
      Uncertainty also remains about the association between many dietary factors, such
      as vitamin C, magnesium, and animal protein, and the risk of kidney stone
      formation. To examine the association between dietary factors and the risk of
      incident, symptomatic kidney stones in men and to determine whether these
      associations vary with age, a prospective cohort study was conducted of 45,619
      men without a history of nephrolithiasis. Self-administered food frequency
      questionnaires were used to assess diet every 4 yr. A total of 1473 incident
      symptomatic kidney stones were documented during 477,700 person-years of follow
      up. For men aged <60 yr, the multivariate relative risk (RR) for stone formation
      in the highest quintile of dietary calcium as compared with the lowest quintile
      was 0.69 (95% confidence interval [CI], 0.56 to 0.87; P = 0.01 for trend). By
      contrast, there was no association between dietary calcium and stone formation in
      men aged 60 yr or older. The multivariate RR for men who consumed 1000 mg or
      greater of vitamin C per day compared with those who consumed less than the
      recommended dietary allowance of 90 mg/d was 1.41 (95% CI, 1.11 to 1.80; P = 0.01
      for trend). Other dietary factors showed the following multivariate RR among men
      in the highest quintile of intake compared with those in the lowest: magnesium,
      0.71 (95% CI, 0.56 to 0.89; P = 0.01 for trend); potassium, 0.54 (95% CI, 0.42 to
      0.68; P < 0.001 for trend); and fluid, 0.71 (95% CI, 0.59 to 0.85; P < 0.001 for
      trend). Animal protein was associated with risk only in men with a body mass
      index <25 kg/m(2) (RR, 1.38; 95% CI, 1.05 to 1.81; P = 0.03 for trend). Sodium,
      phosphorus, sucrose, phytate, vitamin B(6), vitamin D, and supplemental calcium
      were not independently associated with risk. In conclusion, the association
      between calcium intake and kidney stone formation varies with age. Magnesium
      intake decreases and total vitamin C intake seems to increase the risk of
      symptomatic nephrolithiasis. Because age and body size affect the relation
      between diet and kidney stones, dietary recommendations for stone prevention
      should be tailored to the individual patient.

PMID- 15579527
TI  - Insulin resistance after renal transplantation: the effect of steroid dose
      reduction and withdrawal.
AB  - Cardiovascular disease is a prevalent and serious complication after solid organ
      transplantation. Treatment with glucocorticoids is associated with increased risk
      for diabetes mellitus, insulin resistance, weight gain, hypercholesterolemia, and
      hypertension, all shown to be independent risk factors for cardiovascular
      disease. We sought to test the hypothesis that tapering of prednisolone (TAP) the
      first year after renal transplantation improves insulin sensitivity (IS), and to
      assess the effect of complete steroid withdrawal (SW) on IS in patients on a
      cyclosporine-based immunosuppressive regimen. All patients (n = 57) completed two
      consecutive hyperinsulinemic euglycemic glucose clamp procedures, a TAP group (n
      = 34) and a control group (n = 12) at 3 and 12 mo after transplantation, and a SW
      group (n = 11) before and 5 mo after SW. The IS index (ISI) was calculated as the
      glucose disposal rate divided by mean serum insulin the last 60 min of the clamp.
      In the TAP group, the mean (range) daily prednisolone was reduced from 16 (10 to
      30) to 9 (5 to 12.5) mg accompanied by an average increased ISI of 24% (P =
      0.008). In contrast, no significant change in ISI was observed in the control
      group (0%, P = 0.988). In the SW group, withdrawal of 5 mg prednisolone did not
      influence mean ISI significantly (-8%, P = 0.206). Lowering daily prednisolone
      toward 5 mg/d has beneficial effects on insulin action after renal
      transplantation, but withdrawal of 5 mg prednisolone may not influence IS
      significantly.

PMID- 15579528
TI  - Bioinformatic analysis of the urine proteome of acute allograft rejection.
AB  - The urinary proteome in health and disease attracts increasing attention because
      of the potential diagnostic and pathophysiologic biomarker information carried by
      specific excreted proteins or their constellations. This cross-sectional study
      aimed to analyze the urinary proteome in patients with biopsy-proven acute
      rejection (n = 23) compared with transplant recipients with stable graft function
      (n = 22) and healthy volunteers (n = 20) and to correlate this with clinical,
      morphologic, and laboratory data. Urine samples were preadsorbed on four
      different protein chip surfaces, and the protein composition was analyzed using a
      surface-enhanced laser desorption/ionization time-of-flight mass spectrometer
      platform. The data were analyzed using two independent approaches to sample
      classification. Patients who experienced acute rejection could be distinguished
      from stable patients with a sensitivity of 90.5 to 91.3% and a specificity of
      77.2 to 83.3%, depending on the classifier used. Protein masses that were
      important in constructing the classification algorithms included those of mass
      2003.0, 2802.6, 4756.3, 5872.4, 6990.6, 19,018.8, and 25,665.7 Da. Normal urine
      was distinguished from transplant urine using a protein marker of mass 78,531.2
      Da with both a sensitivity and a specificity of 100%. In conclusion, (1) urine
      proteome in transplant recipients with stable graft function was significantly
      different from healthy control subjects, and (2) acute rejections were
      characterized by a constellation of excreted proteins. Analysis of the urinary
      proteome may expedite the noninvasive prediction of acute graft rejection, thus
      importantly assisting in establishing the diagnosis.

PMID- 15579529
TI  - Hepatitis C, acute humoral rejection, and renal allograft survival.
AB  - The effect of recipient hepatitis C virus (HCV) infection on renal allograft loss
      and acute rejection in kidney transplantation remains controversial. We studied
      354 renal allograft recipients transplanted during 1996 to 2001 who had HCV
      antibodies (Ab) measured before transplantation. The primary outcome was death
      censored allograft loss and the secondary outcome was acute humoral rejection
      (AHR). Compared with HCV Ab-negative patients, those with positive HCV Ab had
      longer time on dialysis before transplantation, higher percentage of panel
      reactive antibodies (PRA), were more likely to receive a cadaveric transplant,
      and were more likely to develop delayed graft function (DGF). In univariate
      analyses, predictors of renal allograft loss included HCV, cadaveric graft, PRA
      >20%, HLA mismatch > or =5, retransplantation, DGF, induction therapy, and AHR.
      When adjusted for PRA >20%, HLA mismatch > or =5, and multiple transplant status,
      HCV was not a statistically significant predictor of allograft loss. HCV was also
      associated with AHR but lost significance when adjusted for PRA >20%. HCV Ab
      positive patients were more likely to have longer duration of dialysis before
      transplantation prior to kidney transplants, higher PRA, and to receive cadaveric
      transplants. These characteristics likely resulted in more DGF and AHR after
      transplantation. After adjusting for these confounding factors, the association
      between HCV Ab positivity and renal allograft loss was notably attenuated and no
      longer statistically significant.

PMID- 15579530
TI  - Evaluation of intravenous immunoglobulin as an agent to lower allosensitization
      and improve transplantation in highly sensitized adult patients with end-stage
      renal disease: report of the NIH IG02 trial.
AB  - Reported are the reduction of anti-HLA antibody levels and improvement of
      transplant rates by intravenous immunoglobulin (IVIG) in a randomized, double
      blind, placebo-controlled clinical trial. Between 1997 and 2000, a total of 101
      adult patients with ESRD who were highly sensitized to HLA antigens (panel
      reactive antibody [PRA] > or =50% monthly for 3 mo) enrolled onto an NIH
      sponsored trial (IG02). Patients received IVIG or placebo. Subjects received IVIG
      2 g/kg monthly for 4 mo or an equivalent volume of placebo with additional
      infusions at 12 and 24 mo after entry if not transplanted. If transplanted,
      additional infusions were given monthly for 4 mo. Baseline PRA levels were
      similar in both groups. However, IVIG significantly reduced PRA levels in study
      subjects compared with placebo. Sixteen IVIG patients (35%) and eight placebo
      patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and
      1 of 10 placebo subjects. Seven graft failures occurred (four IVIG, three
      placebo) among adherent patients with similar 2-yr graft survival rates (80%
      IVIG, 75% placebo). With a median follow-up of 2 yr after transplant, the viable
      transplants functioned normally with a mean +/- SEM serum creatinine of 1.68 +/-
      0.28 for IVIG versus 1.28 +/- 0.13 mg/dl for placebo. Adverse events rates were
      similar in both groups. We conclude that IVIG is better than placebo in reducing
      anti-HLA antibody levels and improving transplantation rates in highly sensitized
      patients with ESRD. Transplant rates for highly sensitized patients with ESRD
      awaiting kidney transplants are improved with IVIG therapy.

PMID- 15579531
TI  - Payment for quality in end-stage renal disease.

PMID- 15579532
TI  - Renal transplantation: a half century of success and the long road ahead.

PMID- 15579534
TI  - Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and
      expression of Nav1.5 on the surface of cardiomyocytes.
AB  - We identify a human mutation (E1053K) in the ankyrin-binding motif of Na(v)1.5
      that is associated with Brugada syndrome, a fatal cardiac arrhythmia caused by
      altered function of Na(v)1.5. The E1053K mutation abolishes binding of Na(v)1.5
      to ankyrin-G, and also prevents accumulation of Na(v)1.5 at cell surface sites in
      ventricular cardiomyocytes. Ankyrin-G and Na(v)1.5 are both localized at
      intercalated disc and T-tubule membranes in cardiomyocytes, and Na(v)1.5
      coimmunoprecipitates with 190-kDa ankyrin-G from detergent-soluble lysates from
      rat heart. These data suggest that Na(v)1.5 associates with ankyrin-G and that
      ankyrin-G is required for Na(v)1.5 localization at excitable membranes in
      cardiomyocytes. Together with previous work in neurons, these results in
      cardiomyocytes suggest that ankyrin-G participates in a common pathway for
      localization of voltage-gated Na(v) channels at sites of function in multiple
      excitable cell types.

PMID- 15579535
TI  - Organismal stress and telomeric aging: an unexpected connection.

PMID- 15579536
TI  - Accessibility of mid-segment domain IV S6 residues of the voltage-gated Na+
      channel to methanethiosulfonate reagents.
AB  - The inner pore of the voltage-gated Na+ channel is predicted by the structure of
      bacterial potassium channels to be lined with the four S6 alpha-helical segments.
      Our previously published model of the closed pore based on the KcsA structure,
      and our new model of the open pore based on the MthK structure predict which
      residues in the mid-portion of S6 face the pore. We produced cysteine mutants of
      the mid-portion of domain IV-S6 (Ile-1575-Leu-1591) in NaV 1.4 and tested their
      accessibility to intracellularly and extracellularly placed positively charged
      methanethiosulfonate (MTS) reagents. We found that only two mutants, F1579C and
      V1583C, were accessible to both outside and inside 2-(aminoethyl)
      methanethiosulfonate hydrobromide (MTSEA) Further study of those mutants showed
      that efficient closure of the fast inactivation gate prevented block by inside [2
      (trimethylammonium)ethyl]methanethiosulfonate bromide (MTSET) at slow stimulation
      rates. When fast inactivation was inhibited by exposure to anthropleurin B (ApB),
      increasing channel open time, both mutants were blocked by inside MTSET at a rate
      that depended on the amount of time the channel was open. Consistent with the
      fast inactivation gate limiting access to the pore, in the absence of ApB, inside
      MTSET produced block when the cells were stimulated at 5 or 20 Hz. We therefore
      suggest that the middle of IV-S6 is an alpha-helix, and we propose a model of the
      open channel, based on MthK, in which Phe-1579 and Val-1583 face the pore.

PMID- 15579537
TI  - Multiple regulation by calcium of murine homologues of transient receptor
      potential proteins TRPC6 and TRPC7 expressed in HEK293 cells.
AB  - We investigated, by using the patch clamp technique, Ca2+-mediated regulation of
      heterologously expressed TRPC6 and TRPC7 proteins in HEK293 cells, two closely
      related homologues of the transient receptor potential (TRP) family and molecular
      candidates for native receptor-operated Ca2+ entry channels. With nystatin
      perforated recording, the magnitude and time courses of activation and
      inactivation of carbachol (CCh; 100 microM)-activated TRPC6 currents (I(TRPC6))
      were enhanced and accelerated, respectively, by extracellular Ca2+ (Ca2+(o))
      whether it was continuously present or applied after receptor stimulation. In
      contrast, Ca2+(o) solely inhibited TRPC7 currents (I(TRPC7)). Vigorous buffering
      of intracellular Ca2+ (Ca2+(i)) under conventional whole-cell clamp abolished the
      slow potentiating (i.e. accelerated activation) and inactivating effects of
      Ca2+(o), disclosing fast potentiation (EC50: approximately 0.4 mM) and inhibition
      (IC50: approximately 4 mM) of I(TRPC6) and fast inhibition (IC50: approximately
      0.4 mM) of I(TRPC7). This inhibition of I(TRPC6) and I(TRPC7) seems to be
      associated with voltage-dependent reductions of unitary conductance and open
      probability at the single channel level, whereas the potentiation of I(TRPC6)
      showed little voltage dependence and was mimicked by Sr2+ but not Ba2+. The
      activation process of I(TRPC6) or its acceleration by Ca2+(o) probably involves
      phosphorylation by calmodulin (CaM)-dependent kinase II (CaMKII), as pretreatment
      with calmidazolium (3 microM), coexpression of Ca2+-insensitive mutant CaM, and
      intracellular perfusion of the non-hydrolysable ATP analogue AMP-PNP and a CaMKII
      specific inhibitory peptide all effectively prevented channel activation.
      However, this was not observed for TRPC7. Instead, single CCh-activated TRPC7
      channel activity was concentration-dependently suppressed by nanomolar Ca2+(i)
      via CaM and conversely enhanced by IP3. In addition, the inactivation time course
      of I(TRPC6) was significantly retarded by pharmacological inhibition of protein
      kinase C (PKC). These results collectively suggest that TRPC6 and 7 channels are
      multiply regulated by Ca2+ from both sides of the membrane through differential
      Ca2+-CaM-dependent and -independent mechanisms.

PMID- 15579538
TI  - The alpha 1 and alpha 6 subunit subtypes of the mammalian GABA(A) receptor confer
      distinct channel gating kinetics.
AB  - The GABA(A) receptors show a large degree of structural heterogeneity, with seven
      different subunit families, and 16 different subtypes in mammalian species. The
      alpha family is the largest, with six different subtypes. The alpha1 and alpha6
      subtypes are among the most diverse within this family and confer distinct
      pharmacological properties to recombinant and neuronal receptors. To determine
      whether different single channel and macroscopic kinetic properties were also
      associated with these subtypes, the alpha1 or alpha6 subunit was expressed in
      mammalian cells along with beta3 and gamma2L subunits and the kinetic properties
      examined with outside-out patch recordings. The alpha1 beta3 gamma2L receptors
      responded to GABA with long-duration openings organized into multi-opening
      bursts. In contrast, channel openings of the alpha6 beta3 gamma2L receptors were
      predominately short in duration and occurred as isolated, single openings. The
      subunit subtype also affected the deactivation rate of the receptor, which was
      almost 2-fold slower for alpha6 beta3 gamma2L, compared with the alpha1 beta3
      gamma2L isoform. Onset of fast desensitization did not differ between the
      isoforms. To determine the structural domains responsible for these differences
      in kinetic properties, we constructed six chimeric subunits, combining different
      regions of the alpha1 and alpha6 subunits. The properties of the chimeric
      subunits indicated that structures within the third transmembrane domain (TM3)
      and the TM3-TM4 intracellular loop conferred differences in single channel gating
      kinetics that subsequently affected the deactivation rate and GABA EC50. The
      effect of agonist concentration on the rise time of the current showed that the
      extracellular N-terminal domain was largely responsible for binding
      characteristics, while the transmembrane domains determined the activation rate
      at saturating GABA concentrations. This suggests that subunit structures outside
      of the agonist binding and pore-lining domains are responsible for the kinetic
      differences conferred by the alpha1 and alpha6 subtypes. Structural heterogeneity
      within these transmembrane and intracellular regions can therefore influence the
      characteristics of the postsynaptic response of GABA(A) receptors with different
      subunit composition.

PMID- 15579539
TI  - Cell swelling-induced ATP release is tightly dependent on intracellular calcium
      elevations.
AB  - Mechanical stresses release ATP from a variety of cells by a poorly defined
      mechanism(s). Using custom-designed flow-through chambers, we investigated the
      kinetics of cell swelling-induced ATP secretion, cell volume and intracellular
      calcium changes in epithelial A549 and 16HBE14o- cells, and NIH/3T3 fibroblasts.
      Fifty per cent hypotonic shock triggered transient ATP release from cell
      confluent monolayers, which consistently peaked at around 1 min 45 s for A549 and
      NIH/3T3, and at 3 min for 16HBE14o- cells, then declined to baseline within the
      next 15 min. Whereas the release time course had a similar pattern for the three
      cell types, the peak rates differed significantly (294 +/- 67, 70 +/- 22 and 17
      +/- 2.8 pmol min(-1) (10(6) cells)(-1), for A549, 16HBE14o- and NIH/3T3,
      respectively). The concomitant volume changes of substrate-attached cells were
      analysed by a 3-dimensional cell shape reconstruction method based on images
      acquired from two perpendicular directions. The three cell types swelled at a
      similar rate, reaching maximal expansion in 1 min 45 s, but differed in the
      duration of the volume plateau and regulatory volume decrease (RVD). These
      experiments revealed that ATP release does not correlate with either cell volume
      expansion and the expected activation of stretch-sensitive channels, or with the
      activation of volume-sensitive, 5-nitro-2-(3-phenylpropylamino) benzoic acid
      inhibitable anion channels during RVD. By contrast, ATP release was tightly
      synchronized, in all three cell types, with cytosolic calcium elevations.
      Furthermore, loading A549 cells with the calcium chelator BAPTA significantly
      diminished ATP release (71% inhibition of the peak rate), while the calcium
      ionophore ionomycin triggered ATP release in the absence of cell swelling.
      Lowering the temperature to 10 degrees C almost completely abolished A549 cell
      swelling-induced ATP release (95% inhibition of the peak rate). These results
      strongly suggest that calcium-dependent exocytosis plays a major role in
      mechanosensitive ATP release.

PMID- 15579540
TI  - Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric
      parietal cells.
AB  - Recently, we and others have shown that luminal K+ recycling via KCNQ1 K+
      channels is required for gastric H+ secretion. Inhibition of KCNQ1 by the
      chromanol 293B strongly diminished H+ secretion. The present study aims at
      clarifying KCNQ1 subunit composition, subcellular localization, regulation and
      pharmacology in parietal cells. Using in situ hybridization and
      immunofluorescence techniques, we identified KCNE2 as the beta subunit of KCNQ1
      in the luminal membrane compartment of parietal cells. Expressed in COS cells,
      hKCNE2/hKCNQ1 channels were activated by acidic pH, PIP2, cAMP and purinergic
      receptor stimulation. Qualitatively similar results were obtained in mouse
      parietal cells. Confocal microscopy revealed stimulation-induced translocation of
      H+,K+-ATPase from tubulovesicles towards the luminal pole of parietal cells,
      whereas distribution of KCNQ1 K+ channels did not change to the same extent. In
      COS cells the 293B-related substance IKs124 blocked hKCNE2/hKCNQ1 with an IC50 of
      8 nM. Inhibition of hKCNE1- and hKCNE3-containing channels was weaker with IC50
      values of 370 and 440 nM, respectively. In conclusion, KCNQ1 coassembles with
      KCNE2 to form acid-activated luminal K+ channels of parietal cells. KCNQ1/KCNE2
      is activated during acid secretion via several pathways but probably not by
      targeting of the channel to the membrane. IKs124 could serve as a leading
      compound in the development of subunit-specific KCNE2/KCNQ1 blockers to treat
      peptic ulcers.

PMID- 15579541
TI  - Concentration polarization of hyaluronan on the surface of the synovial lining of
      infused joints.
AB  - Hyaluronan (HA) in joints conserves the lubricating synovial fluid by making
      trans-synovial fluid escape almost insensitive to pressure elevation (e.g.
      effusions, joint flexion). This phenomenon, 'outflow buffering', was discovered
      during HA infusion into the rabbit knee joint cavity. It was also found that HA
      is partially reflected by the joint lining (molecular sieving), and that the
      reflected fraction R decreases as trans-synovial filtration rate Q is increased.
      It was postulated therefore that outflow buffering is mediated by HA reflection.
      Reflection creates a HA concentration polarization layer, the osmotic pressure of
      which opposes fluid loss. A steady-state, cross-flow ultrafiltration model was
      previously used to explain the outflow buffering and negative R-vs.-Q relation.
      However, the steady-state, cross-perfusion assumptions restricted the model's
      applicability for an infused, dead-end cavity or a non-infused joint during
      cyclical motion. We therefore developed a new, non-steady-state model which
      describes the time course of dead-end, partial HA ultrafiltration. The model
      describes the progressive build-up of a HA concentration polarization layer at
      the synovial surface over time. Using experimental parameter values, the model
      successfully accounts for the observed negative R-vs.-Q relation and shows that
      the HA reflected fraction (R) also depends on HA diffusivity, membrane area
      expansion and the synovial HA reflection coefficient. The non-steady-state model
      thus explains existing experimental work, and it is a key stage in understanding
      synovial fluid turnover in intact, moving, human joints or osteoarthritic joints
      treated by HA injections.

PMID- 15579542
TI  - Nitric oxide is significantly reduced in ex vivo porcine arteries during reverse
      flow because of increased superoxide production.
AB  - Oscillatory and negative flows occur normally in the cardiovascular system, which
      predispose those regions to atherosclerosis. Nitric oxide (NO) production
      increases in proportion to the magnitude of flow and is known to be athero
      protective. What is not known, however, is the effect of flow reversal on NO
      concentration ([NO]). The hypothesis of the present study is that [NO] is reduced
      in reverse flow. An additional hypothesis is that the reduction in [NO] is
      mediated through an increase in superoxide production during flow reversal. These
      hypotheses were tested in an ex vivo preparation of porcine elastic and muscular
      arteries. The flow of a physiological solution through the vessels was regulated
      in the forward and reverse direction and the effluent was assayed for nitrite
      levels using a combination of a diazo coupling method and high performance liquid
      chromatography. Our results show that [NO] is significantly reduced during
      reverse flow. Furthermore, addition of tempol (superoxide dismutase-mimetic)
      which is a superoxide scavenger returns the [NO] during reverse flow to mirror
      those of forward flow. These results have important implications since the action
      of superoxide is implicated in many cardiovascular diseases, and the present
      finding suggests that flow reversal should be added to the list.

PMID- 15579543
TI  - Pharyngeal airway wall mechanics using tagged magnetic resonance imaging during
      medial hypoglossal nerve stimulation in rats.
AB  - To better understand pharyngeal airway mechanics as it relates to the
      pathogenesis and treatment of obstructive sleep apnoea, we have developed a novel
      application of magnetic resonance imaging (MRI) with non-invasive tissue tagging
      to measure pharyngeal wall tissue motion during active dilatation of the airway.
      Eleven anaesthetized Sprague-Dawley rats were surgically prepared with platinum
      electrodes for bilateral stimulation of the medial branch of the hypoglossus
      nerve that supplies motor output to the protrudor and intrinsic tongue muscles.
      Images of the pharyngeal airway were acquired before and during stimulation using
      a gated multislice, spoiled gradient recalled (SPGR) imaging protocol in a 4.7 T
      magnet. The tag pulses, applied before stimulation, created a grid pattern of
      magnetically imbedded dark lines that revealed tissue motion in images acquired
      during stimulation. Stimulation significantly increased cross-sectional area, and
      anteroposterior and lateral dimensions in the oropharyngeal and velopharyngeal
      airways when results were averaged across the rostral, mid- and caudal pharynx (P
      < 0.001). Customized software for tissue motion-tracking and finite element
      analysis showed that changes in airway size were associated with ventral
      displacement of tissues in the ventral pharyngeal wall in the rostral, mid- and
      caudal pharyngeal regions (P < 0.0032) and ventral displacement of the lateral
      walls in the mid- and caudal regions (P < 0.0001). In addition, principal maximum
      stretch was significantly increased in the lateral walls (P < 0.023) in a ventral
      lateral direction in the mid- and caudal pharyngeal regions and principal maximum
      compression (perpendicular to stretch) was significantly increased in the ventral
      walls in all regions (P < 0.0001). Stimulation did not cause lateral displacement
      of the lateral pharyngeal walls at any level. The results reveal that the
      increase in pharyngeal airway size resulting from stimulation of the medial
      branch of the hypoglossal nerve is predominantly due to ventral displacement of
      the ventral and lateral pharyngeal walls.

PMID- 15579544
TI  - Muscle pyruvate availability can limit the flux, but not activation, of the
      pyruvate dehydrogenase complex during submaximal exercise in humans.
AB  - While lowering muscle glycogen availability to an extent that would reduce muscle
      pyruvate formation during intense exercise, we investigated the importance of
      muscle pyruvate availability to pyruvate dehydrogenase complex (PDC) activation
      during intense exercise in human skeletal muscle. The present study demonstrated
      that regardless of whether pre-exercise muscle glycogen content was at a habitual
      resting concentration (412 +/- 30 mmol (kg dry muscle)(-1)) or depleted (60 +/- 3
      mmol (kg dry muscle)(-1)), the increase in PDC activation from its resting value
      (5.46 +/- 0.96 and 3.67 +/- 0.34 nmol acetyl-CoA min(-1) (mg protein)(-1),
      respectively) during 10 min of exercise at 75% of the maximum rate of oxygen
      consumption (VO2max) (delta12.82 +/- 1.72 and delta13.24 +/- 1.42 nmol acetyl-CoA
      min(-1) (mg protein)(-1), respectively) was the same, despite pyruvate
      accumulation during exercise being 3-fold lower in the glycogen depleted state
      (delta0.34 +/- 0.04 and delta0.11 +/- 0.06 mmol (kg dry muscle)(-1), P < 0.001).
      However, as a result of the reduction in pyruvate availability, calculated flux
      through the PDC reaction was at least 2-fold lower in the glycogen depleted state
      compared with normal (21.81 +/- 2.62 and 9.41 +/- 0.63 nmol acetyl-CoA min(-1)
      (mg protein)(-1), respectively; P < 0.001). It is therefore pertinent to conclude
      that whilst muscle pyruvate availability appears to be important to the rate of
      flux through the PDC reaction during in vivo contraction, it is not of primary
      importance to the control of PDC activation under these conditions, which is
      probably principally regulated by muscle calcium availability. The proposed
      central role of pyruvate in muscle PDC activation during in vivo contraction may
      therefore have been over stated.

PMID- 15579545
TI  - Ammonia excretion in aquatic and terrestrial crabs.
AB  - The excretory transport of toxic ammonia across epithelia is not fully
      understood. This review presents data combined with models of ammonia excretion
      derived from studies on decapod crabs, with a view to providing new impetus to
      investigation of this essential issue. The majority of crabs preserve ammonotely
      regardless of their habitat, which varies from extreme hypersaline to freshwater
      aquatic environments, and ranges from transient air exposure to obligate air
      breathing. Important components in the excretory process are the Na+/K+(NH4+)
      ATPase and other membrane-bound transport proteins identified in many species, an
      exocytotic ammonia excretion mechanism thought to function in gills of aquatic
      crabs such as Carcinus maenas, and gaseous ammonia release found in terrestrial
      crabs, such as Geograpsus grayi and Ocypode quadrata. In addition, this review
      presents evidence for a crustacean Rhesus-like protein that shows high homology
      to the human Rhesus-like ammonia transporter both in its amino acid sequence and
      in its predicted secondary structure.

PMID- 15579546
TI  - Enhancement of twitch force by stretch in a nerve-skeletal muscle preparation of
      the frog Rana porosa brevipoda and the effects of temperature on it.
AB  - We investigated the mechanism of the enhancement of twitch force by stretch and
      the effects of temperature on it in nerve-skeletal muscle preparations of whole
      iliofibularis muscles isolated from the frog Rana brevipoda. When a preparation
      was stimulated indirectly and stretched, the twitch force after the stretch was
      enhanced remarkably in comparison to that observed before a stretch at low
      temperature. The enhanced force obtained by a stretch of 20% resting muscle
      length (l0) at low temperature was as high as the force obtained by direct
      stimulation. The phenomenon was not dependent on the velocity but on the
      amplitude of stretch. The enhanced force obeyed the length-force relationship
      when a stretch was long enough. The above results were observed when the frogs
      were kept at room temperature (20-22 degrees C). Measurements were also taken at
      low temperature (4 degrees C); when frogs were kept at low temperature for more
      than 2 months, twitch force obtained without stretch was considerably higher at
      l0. The amplitude of the action potential recorded extracellularly from the
      muscle surface increased remarkably after a stretch, but was same before and
      after a stretch when recorded from the nerve innervating muscle. The effects of
      temperature on twitch and tetanic force by direct or indirect stimulation without
      stretch were also studied as basic data of the stretch experiment. The results
      from this study suggest that stretch-induced force enhancement in a nerve-muscle
      preparation is caused by an increase in the transmission rate between nerve and
      muscle, and the amplitude of the enhanced force is determined by the length-force
      relationship of the muscle. The phenomenon is also strongly affected by the
      temperature at which the frogs are kept.

PMID- 15579547
TI  - Kinetics and rhythm of body contractions in the sponge Tethya wilhelma (Porifera:
      Demospongiae).
AB  - Sponges of the species Tethya wilhelma display rhythmic body contractions, which
      were analyzed by digital timelapse imaging and semi-automated image analysis. For
      the first time, differential, quantitative data on sponge behaviour could be
      obtained. The sponges are able to reduce their body volume by up to 73.3% during
      regular contractions. Each contraction cycle follows a characteristic pattern of
      four phases, permitting analysis of the kinetics of contraction and expansion.
      Long-term observations (for >7 days) reveal that the sponge contractions display
      a day-night periodicity in which contraction cycles are significantly longer
      during the dark hours. The contractions seem to be mediated by the pinacoderm;
      they are triggered locally and spread over the sponge surface at 12.5 microm s(
      1). If two individuals of a clone are fused, the individual contraction rhythm of
      both sponges persists for several days, until a single new individual sponge is
      formed with a synchronized rhythm. The reported results and techniques establish
      T. wilhelma as a model organism for research on the development of aneural signal
      transduction and integration during early Metazoan evolution.

PMID- 15579548
TI  - Metabolism of normothermic woodchucks during prolonged fasting.
AB  - The energy metabolism of hibernators has not been characterized for normothermic
      fasting, and our goal was to quantify oxidative fuel selection of non-hibernating
      woodchucks Marmota monax during prolonged food deprivation. Indirect calorimetry
      and nitrogen excretion measurements were used to assess changes in metabolic rate
      (VO2), fuel selection and composition of nitrogen wastes, as well as seasonal
      differences. For reference, matching experiments were also performed on rabbits.
      The results show that woodchucks have a higher metabolic rate in summer (271
      micromol O2 kg(-1) min(-1)) than in spring (200 micromol O2 kg(-1) min(-1)) and
      that fasting-induced metabolic depression is only possible in summer (-25% in 14
      days). The metabolic rate of rabbits is high at all times (383 micromol O2 kg(-1)
      min(-1)), but they show a more rapid depression in response to fasting (-32% in 7
      days). Woodchucks have a naturally low reliance on proteins in the fed state
      (accounting for 8% VO2) in spring; 17% VO2 in summer; vs 28% VO2 in rabbits) and
      are able to decrease it even further during fasting (spring, 5% VO2); summer, 6%
      VO2; vs 20% VO2 in rabbits). This study shows that, apart from their notorious
      capacity for hibernation, woodchucks are particularly well adapted for
      normothermic fasting. Their ability to cope with prolonged food deprivation is
      based on a series of integrated responses eliciting deep metabolic depression and
      a rapid change in fuel selection to spare limited protein reserves. Information
      presently available on prolonged fasting suggests that such an ability for
      metabolic depression, possibly down to minimal levels still compatible with
      normothermic life, may be common among mammals. In contrast, the extreme protein
      sparing demonstrated in woodchucks is a unique metabolic feature of fasting
      champions.

PMID- 15579549
TI  - A cephalic projection neuron involved in locomotion is dye coupled to the
      dopaminergic neural network in the medicinal leech.
AB  - It is widely appreciated that the selection and modulation of locomotor circuits
      are dependent on the actions of higher-order projection neurons. In the leech,
      Hirudo medicinalis, locomotion is modulated by a number of cephalic projection
      neurons that descend from the subesophageal ganglion in the head. Specifically,
      descending brain interneuron Tr2 functions as a command-like neuron that can
      terminate or sometimes trigger fictive swimming. In this study, we demonstrate
      that Tr2 is dye coupled to the dopaminergic neural network distributed in the
      head brain. These findings represent the first anatomical evidence in support of
      dopamine (DA) playing a role in the modulation of locomotion in the leech. In
      addition, we have determined that bath application of DA to the brain and entire
      nerve cord reliably and rapidly terminates swimming in all preparations
      exhibiting fictive swimming. By contrast, DA application to nerve cords
      expressing ongoing fictive crawling does not inhibit this motor rhythm.
      Furthermore, we show that Tr2 receives rhythmic feedback from the crawl central
      pattern generator. For example, Tr2 receives inhibitory post-synaptic potentials
      during the elongation phase of each crawl cycle. When crawling is not expressed,
      spontaneous inhibitory post-synaptic potentials in Tr2 correlate in time with
      spontaneous excitatory post-synaptic potentials in the CV motor neuron, a
      circular muscle excitor that bursts during the elongation phase of crawling. Our
      data are consistent with the idea that DA biases the nervous system to produce
      locomotion in the form of crawling.

PMID- 15579550
TI  - Anatomy of a live invertebrate revealed by manganese-enhanced Magnetic Resonance
      Imaging.
AB  - Non-invasive imaging technologies such as Magnetic Resonance Imaging (MRI) are
      increasingly in demand by researchers in many biological disciplines. However,
      when imaging small animals such as invertebrates, not only is the use of high
      field magnets necessary to gain satisfactory spatial resolution, but the
      achievement of adequate contrast between tissues also requires the identification
      of applicable imaging parameters by means of expensive and time-consuming
      procedures. Here we report that systemically administered manganese can act as an
      effective MRI contrast agent for quick and non-invasive imaging of the nervous
      system and other complex anatomical structures in a small aquatic animal. Due to
      the tendency of manganese ions to differentially accumulate in most soft tissues,
      higher overall signal intensity and strongly improved contrast between structures
      yield data well suited for digital post-processing into three-dimensional models.
      Within a few hours this technique can efficiently generate anatomical images that
      are not obtainable with conventional methods, thus demonstrating a new and
      exciting approach to invertebrate research.

PMID- 15579551
TI  - Partitioning heat loss from mallard ducklings swimming on the air-water
      interface.
AB  - Water birds whose young begin swimming while downy are interesting because
      hypothermia and mortality are associated with wetting. While wetting is known to
      increase heat loss, little is known about basic issues, such as the amount of
      heat lost to air vs water during surface swimming. To partition heat loss to air
      and water, we measured the body temperature, metabolism and thermal conductance
      of 2-3-day-old mallard ducklings (Anas platyrhynchos) swimming under different
      combinations of air and water temperature. Ventral down remained dry or was
      wetted only on the surface, and most ducklings could maintain Tb>39 degrees C for
      1 h while swimming on water as cold as 5 degrees C. Ducklings were at or below
      thermal neutrality when swimming in water at Tw=30 degrees C even when air
      temperature Ta=45 degrees C. Heat loss from ducklings with dry down to air and
      water was partitioned by fitting data to a heat transfer model of the form M=G(Tb
      Tw)+Ke(Tb-Ta). For an average 48 g duckling, thermal conductance to water
      increased with water temperature, G=0.0470(1+1.059 x 10(-6)Tw4)W/ degrees C
      animal. Conductance to air was Ke=0.0196 W/ degrees C-animal for all air
      temperatures. Thus, a minimum of 70% of metabolic heat production is lost to
      water, and this fraction increases with increasing temperature.

PMID- 15579552
TI  - A GPI-linked carbonic anhydrase expressed in the larval mosquito midgut.
AB  - We have previously described the first cloning and partial characterization of
      carbonic anhydrase from larval Aedes aegypti mosquitoes. Larval mosquitoes
      utilize an alkaline digestive environment in the lumen of their anterior midgut,
      and we have also demonstrated a critical link between alkalization of the gut and
      carbonic anhydrase(s). In this report we further examine the nature of the
      previously described carbonic anhydrase and test the hypothesis that its pattern
      of expression is consistent with a role in gut alkalization. Additionally we take
      advantage of the recently published genome of the mosquito Anopheles gambiae to
      assess the complexity of the carbonic anhydrase gene family in these insects. We
      report here that the previously described carbonic anhydrase from Aedes aegypti
      is similar to mammalian CA IV in that it is a GPI-linked peripheral membrane
      protein. In situ hybridization analyses identify multiple locations of carbonic
      anhydrase expression in the larval mosquito. An antibody prepared against a
      peptide sequence specific to the Aedes aegypti GPI-linked carbonic anhydrase
      labels plasma membranes of a number of cell types including neuronal cells and
      muscles. A previously undescribed subset of gut muscles is specifically
      identified by carbonic anhydrase immunohistochemistry. Bioinformatic analyses
      using the Ensembl automatic analysis pipeline show that there are at least 14
      carbonic anhydrase genes in the Anopheles gambiae genome, including a homologue
      to the GPI-linked gene product described herein. Therefore, as in mammals which
      similarly possess numerous carbonic anhydrase genes, insects require a large
      family of these genes to handle the complex metabolic pathways influenced by
      carbonic anhydrases and their substrates.

PMID- 15579553
TI  - Functional characterisation of the Anopheles leucokinins and their cognate G
      protein coupled receptor.
AB  - Identification of the Anopheles gambiae leucokinin gene from the completed A.
      gambiae genome revealed that this insect species contains three leucokinin
      peptides, named Anopheles leucokinin I-III. These peptides are similar to those
      identified in two other mosquito species, Aedes aegypti and Culex salinarius.
      Additionally, Anopheles leucokinin I displays sequence similarity to Drosophila
      melanogaster leucokinin. Using a combination of computational and molecular
      approaches, a full-length cDNA for a candidate leucokinin-like receptor was
      isolated from A. stephensi, a close relative of A. gambiae. Alignment of the
      known leucokinin receptors--all G protein-coupled receptors (GPCRs)--with this
      receptor, identified some key conserved regions within the receptors, notably
      transmembrane (TM) domains I, II, III, VI and VII. The Anopheles leucokinins and
      receptor were shown to be a functional receptor-ligand pair. All three Anopheles
      leucokinins caused a dose-dependent rise in intracellular calcium ([Ca2+]i) when
      applied to S2 cells co-expressing the receptor and an aequorin transgene, with a
      potency order of I>II>III. Drosophila leucokinin was also found to activate the
      Anopheles receptor with a similar EC50 value to Anopheles leucokinin I. However,
      when the Anopheles peptides were applied to the Drosophila receptor, only
      Anopheles leucokinin I and II elicited a rise in [Ca2+]i. This suggests that the
      Anopheles receptor has a broader specificity for leucokinin ligands than the
      Drosophila receptor. Antisera raised against the Anopheles receptor identified a
      doublet of approx. 65 and 72 kDa on western blots, consistent with the presence
      of four N-glycosylation sites within the receptor sequence, and the known
      glycosylation of the receptor in Drosophila. In Anopheles tubules, as in
      Drosophila, the receptor was localised to the stellate cells. Thus we provide the
      first identification of Anopheles mosquito leucokinins (Anopheles leucokinins)
      and a cognate leucokinin receptor, characterise their interaction and show that
      Dipteran leucokinin signalling is closely conserved between Drosophila and
      Anopheles.

PMID- 15579554
TI  - Multiple cone visual pigments and the potential for trichromatic colour vision in
      two species of elasmobranch.
AB  - Elasmobranchs (sharks, skates and rays) are the modern descendents of the first
      jawed vertebrates and, as apex predators, often occupy the highest trophic levels
      of aquatic (predominantly marine) ecosystems. However, despite their crucial role
      in the structure of marine communities, their importance both to commercial and
      to recreational fisheries, and the inherent interest in their role in vertebrate
      evolution, very little is known about their visual capabilities, especially with
      regard to whether or not they have the potential for colour vision. Using
      microspectrophotometry, we show that the retinae of the giant shovelnose ray
      (Rhinobatos typus) and the eastern shovelnose ray (Aptychotrema rostrata) contain
      three spectrally distinct cone visual pigments with wavelengths of maximum
      absorbance (lambdamax) at 477, 502 and 561 nm and at 459, 492 and 553 nm,
      respectively. The retinae of R. typus and A. rostrata also contain a single type
      of rod visual pigment with lambdamax at 504 and 498 nm, respectively. R. typus,
      living in the same estuarine waters as A. rostrata, were found to have identical
      visual pigments to R. typus inhabiting coral reef flats, despite a considerable
      difference in habitat spectral radiance. This is the first time that multiple
      cone visual pigments have been measured directly in an elasmobranch. The finding
      raises the possibility that some species are able to discriminate colour--a
      visual ability traditionally thought to be lacking in this vertebrate class--and
      it is evident that the visual ecology of elasmobranchs is far more complex than
      once thought.

PMID- 15579555
TI  - Vestibular compensation in lampreys: restoration of symmetry in reticulospinal
      commands.
AB  - Removal of a vestibular organ (unilateral labyrinthectomy, UL) in the lamprey
      results in a loss of equilibrium, so that the animal rolls (rotates around its
      longitudinal axis) when swimming. Owing to vestibular compensation, UL animals
      gradually restore postural equilibrium and, in a few weeks, swim without rolling.
      Important elements of the postural network in the lamprey are the reticulospinal
      (RS) neurons, which are driven by vestibular input and transmit commands for
      postural corrections to the spinal cord. As shown previously, a loss of
      equilibrium after UL is associated with disappearance of vestibular responses in
      the contralateral group of RS neurons. Are these responses restored in animals
      after compensation? To answer this question, we recorded vestibular responses in
      RS neurons (elicited by rotation of the compensated animal in the roll plane) by
      means of chronically implanted electrodes. We found that the responses re
      appeared in the compensated animals. This result supports the hypothesis that the
      loss of equilibrium after UL was caused by asymmetry in supraspinal motor
      commands, and the recovery of postural control in compensated animals was due to
      a restoration of symmetry.

PMID- 15579556
TI  - Exposure to air, but not seawater, increases the glutamine content and the
      glutamine synthetase activity in the marsh clam Polymesoda expansa.
AB  - Polymesoda expansa spends a considerable portion of its life exposed to air in
      mangrove swamps where salinity fluctuates greatly. Thus, the aim of this study
      was to evaluate the effects of aerial exposure (transfer from 10 per thousand
      brackish water directly to air) or salinity changes (transfer from 10 per
      thousand brackish water directly to 30 per thousand seawater) on nitrogen
      metabolism in P. expansa. We concluded that P. expansa is non-ureogenic because
      carbamoyl phosphate (CPS) III activity was undetectable in the adductor muscle,
      foot muscle, hepatopancreas and mantle when exposed to brackish water (control),
      seawater or air for 17 days. It is ammonotelic as it excretes nitrogenous wastes
      mainly as ammonia in brackish water or seawater. After transfer to seawater for
      17 days, the contents of total free amino acids (TFAA) in the adductor muscle,
      foot muscle, hepatopancreas and mantle increased significantly. This could be
      related to an increase in protein degradation because exposure to seawater led to
      a greater rate of ammonia excretion on days 15 and 17, despite unchanged tissue
      ammonia contents. Alanine was the major free amino acid (FAA) in P. expansa. The
      contribution of alanine to the TFAA pool in various tissues increased from 43-48%
      in brackish water to 62-73% in seawater. In contrast, in clams exposed to air for
      17 days there were no changes in alanine content in any of the tissues studied.
      Thus, the functional role of alanine in P. expansa is mainly connected with
      intracellular osmoregulation. Although 8.5-16.1% of the TFAA pool of P. expansa
      was attributable to glutamine, the glutamine contents in the adductor muscle,
      foot muscle, hepatopancreas and mantle were unaffected by 17 days of exposure to
      seawater. However, after exposure to air for 17 days, there were significant
      increases in ammonia content in all these tissues in P. expansa, accompanied by
      significant increases in glutamine content (2.9-, 2.5-, 4.5- and 3.4-fold,
      respectively). Simultaneously, there were significant increases in glutamine
      synthetase activities in the adductor muscle (1.56-fold) and hepatopancreas (3.8
      fold). This is the first report on the accumulation of glutamine associated with
      an upregulation of glutamine synthetase in a bivalve species in response to
      aerial exposure, and these results reveal that the evolution of glutamine
      synthesis as a means for detoxification of ammonia first occurred among
      invertebrates.

PMID- 15579557
TI  - Lactate availability is not the major factor limiting muscle glycogen repletion
      during recovery from an intense sprint in previously active fasted rats.
AB  - It is not clear whether the amount of accumulated lactate is the main factor
      limiting muscle glycogen accumulation during recovery from an intense sprint
      performed by previously active fasted laboratory rats. To address this question,
      groups of fasted rats swam at moderate intensity for 30 min, each animal with a
      lead weight equivalent to 0.5% body mass attached to its tail, followed by a 3
      min high intensity swim with a 10% lead weight and a recovery period of up to 2
      hours afterwards. Moderately intense exercise for 30 min caused a decrease in
      muscle glycogen levels in the mixed, white and red gastrocnemius and the mixed
      quadriceps muscles, and a further rapid fall occurred in response to the 3 min
      sprint effort. During recovery, glycogen increased to comparable or above pre
      sprint levels across all muscles, and this occurred to a large extent at the
      expense of net carbon sources other than lactate, with these carbon sources
      accounting for at least 36-65% of the glycogen deposited. The sustained
      dephosphorylation-mediated activation of glycogen synthase, but not the changes
      in glucose 6-phosphate levels, most probably played an important role in enabling
      the replenishment of muscle glycogen stores. In conclusion, our findings suggest
      that the amount of glycogen deposited during recovery from high intensity
      exercise in fasted animals is not limited by the amount of accumulated lactate.

PMID- 15579558
TI  - Ion-motive ATPases and active, transbranchial NaCl uptake in the red freshwater
      crab, Dilocarcinus pagei (Decapoda, Trichodactylidae).
AB  - The present investigation examined the microanatomy and mRNA expression and
      activity of ion-motive ATPases, in anterior and posterior gills of a South
      American, true freshwater crab, Dilocarcinus pagei. Like diadromous crabs, the
      anterior gills of this hololimnetic trichodactylid exhibit a highly attenuated (2
      5 microm), symmetrical epithelium on both lamellar surfaces. In sharp contrast,
      the posterior gill lamellar epithelia are markedly asymmetrical. Their proximal
      side consists of thick (18-20 microm) cells, displaying features typical of a
      transporting epithelium, while the distal epithelium is thin (3-10 microm) and
      formed entirely by apical pillar cell flanges. Both anterior and posterior gills
      express Na+/K+- and V-ATPases. Phylogenetic analysis of partial cDNA sequences
      for the Na+/K+-ATPase alpha-subunit and V-ATPase B-subunit among various crab
      species confirmed the previous classification and grouping of D. pagei based on
      morphological criteria. Semi-quantitative RT-PCR clearly showed that mRNA for
      both ion pump subunits is more intensely expressed in posterior gills. Na+/K+
      ATPase activity in the posterior gills was nearly fourfold that of anterior
      gills, while V-ATPase and F-ATPase activities did not differ. A negative short
      circuit current (Isc) was measured using the distal side of split, posterior gill
      lamellae, mounted in a modified Ussing chamber and perfused symmetrically with
      identical hemolymph-like salines. Although hemolymph-side ouabain did not affect
      this current, concanamycin significantly reduced Isc without altering preparation
      conductance, suggesting V-ATPase-driven Cl- absorption on the distal side of the
      posterior gill lamellae, as known to occur in diadromous crabs adapted to
      freshwater. These findings suggest that active Na+ uptake predominates across the
      thick proximal epithelium, and Cl- uptake across the thin, distal epithelium of
      the posterior gill lamellae.

PMID- 15579559
TI  - Cold-stable eye lens crystallins of the Antarctic nototheniid toothfish
      Dissostichus mawsoni Norman.
AB  - The eye lenses of the Antarctic nototheniid fishes that inhabit the perennially
      freezing Antarctic seawater are transparent at -2 degrees C, whereas the cold
      sensitive mammalian and tropical fish lenses display cold-induced cataract at 20
      degrees C and 7 degrees C, respectively. No cold-cataract occurs in the giant
      Antarctic toothfish Dissostichus mawsoni lens when cooled to temperatures as low
      as -12 degrees C, indicating highly cold-stable lens proteins. To investigate
      this cold stability, we characterised the lens crystallin proteins of the
      Antarctic toothfish, in parallel with those of the sub-tropical bigeye tuna
      Thunnus obesus and the endothermic cow Bos taurus, representing three disparate
      thermal climes (-2 degrees C, 18 degrees C and 37 degrees C, respectively).
      Sizing chromatography resolved their lens crystallins into three groups,
      alpha/betaH, beta and gamma, with gamma crystallins being the most abundant
      (>40%) lens proteins in fish, in contrast to the cow lens where they comprise
      only 19%. The upper thermal stability of these crystallin components correlated
      with the body temperature of the species. In vitro chaperone assays showed that
      fish alpha crystallin can protect same-species gamma crystallins from heat
      denaturation, as well as lysozyme from DTT-induced unfolding, and therefore are
      small Heat Shock Proteins (sHSP) like their mammalian counterparts. Dynamic light
      scattering measured an increase in size of alphagamma crystallin mixtures upon
      heating, which supports formation of the alphagamma complex as an integral part
      of the chaperone process. Surprisingly, in cross-species chaperone assays, tuna
      alpha crystallins only partly protected toothfish gamma crystallins, while cow
      alpha crystallins completely failed to protect, indicating partial and no
      alphagamma interaction, respectively. Toothfish gamma was likely to be the
      component that failed to interact, as the supernatant from a cow alpha plus
      toothfish gamma incubation could chaperone cow gamma crystallins in a subsequent
      heat incubation, indicating the presence of uncomplexed cow alpha. This suggests
      that the inability of toothfish gamma crystallins to fully complex with tuna
      alpha, and not at all with the cow alpha crystallins, may have its basis in
      adaptive changes in the protein that relate to the extreme cold-stability of the
      toothfish lens.

PMID- 15579560
TI  - Submaximal power output from the dorsolongitudinal flight muscles of the hawkmoth
      Manduca sexta.
AB  - To assess the extent to which the power output of a synchronous insect flight
      muscle is maximized during flight, we compared the maximum potential power output
      of the mesothoracic dorsolongitudinal (dl1) muscles of Manduca sexta to their
      power output in vivo. Holding temperature and cycle frequency constant at 36
      degrees C and 25 Hz, respectively, we varied the phase of activation, mean length
      and strain amplitude. Under in vivo conditions measured in tethered flight, the
      dl1 muscles generated only 40-67% of their maximum potential power output.
      Compared to the in vivo phase of activation, the phase that maximized power
      output was advanced by 12% of the cycle period, and the length that maximized
      power output was 10% longer than the in vivo operating length.

PMID- 15579561
TI  - Neuronal and neurohormonal control of the heart in the stomatopod crustacean,
      Squilla oratoria.
AB  - The heart of Squilla oratoria contains a cardiac ganglion that consists of 15
      intrinsic neurons, supplied by a pair of inhibitory nerves and two pairs of
      excitatory nerves, arising from the central nervous system. These comprise the
      extrinsic cardiac innervation. The paired cardio-inhibitor (CI) nerves run out in
      the 10th pair of nerve roots emerging from the subesophageal ganglion (SEG). The
      cell bodies of the CI neurons are found in the hemisphere of the 1st segment of
      the SEG contralateral to the nerve roots in which the CI axons emerge. The two
      pairs of 1st and 2nd cardio-accelerator (CA1 and CA2) nerves run out in the 16th
      and 19th pairs of nerve roots of the SEG. The cell bodies of the CA1 and CA2
      neurons are found in the hemispheres of the 3rd and 4th segments of the SEG
      ipsilateral to the nerve roots in which the CA1 and CA2 axons are found. The
      heartbeat was activated by application of glutamate, serotonin, dopamine,
      octopamine or acetylcholine, which were applied to the heart by perfusion into an
      organ bath. Joro-spider toxin (JSTX) blocked myocardial excitatory junctional
      potentials evoked by the cardiac ganglion. Neuronal cell bodies and processes in
      the heart were examined using immunocytochemical techniques. All 15 neurons of
      the cardiac ganglion showed glutamate-like immunoreactivity. Glutamate may be a
      neurotransmitter of the cardiac ganglion neurons. JSTX also blocked cardiac
      acceleration by activation of CA1 and CA2 axons. CA1 and CA2 axons showed
      glutamate-like immunoreactivity. It is likely that glutamate is a
      neurotransmitter for the cardio-acceleratory neurons. The heartbeat was inhibited
      by application of gamma-amino-butyric acid (GABA). Cardiac inhibition induced by
      activation of CI axons was blocked by picrotoxin. CI axons showed GABA-like
      immunoreactivity. These results may support the identification of GABA as an
      extrinsic inhibitory neurotransmitter.

PMID- 15579562
TI  - Stroke patterns and regulation of swim speed and energy cost in free-ranging
      Brunnich's guillemots.
AB  - Loggers were attached to free-ranging Brunnich's guillemots Uria lomvia during
      dives, to measure swim speeds, body angles, stroke rates, stroke and glide
      durations, and acceleration patterns within strokes, and the data were used to
      model the mechanical costs of propelling the body fuselage (head and trunk
      excluding wings). During vertical dives to 102-135 m, guillemots regulated their
      speed during descent and much of ascent to about 1.6+/-0.2 m s(-1). Stroke rate
      declined very gradually with depth, with little or no gliding between strokes.
      Entire strokes from 2 m to 20 m depth had similar forward thrust on upstroke vs
      downstroke, whereas at deeper depths and during horizontal swimming there was
      much greater thrust on the downstroke. Despite this distinct transition, these
      differences had small effect (<6%) on our estimates of mechanical cost to propel
      the body fuselage, which did not include drag of the wings. Work stroke(-1) was
      quite high as speed increased dramatically in the first 5 m of descent against
      high buoyancy. Thereafter, speed and associated drag increased gradually as
      buoyancy slowly declined, so that mechanical work stroke(-1) during the rest of
      descent stayed relatively constant. Similar work stroke(-1) was maintained during
      non-pursuit swimming at the bottom, and during powered ascent to the depth of
      neutral buoyancy (about 71 m). Even with adjustments in respiratory air volume of
      +/-60%, modeled work against buoyancy was important mainly in the top 15 m of
      descent, after which almost all work was against drag. Drag was in fact
      underestimated, as our values did not include enhancement of drag by altered flow
      around active swimmers. With increasing buoyancy during ascent above 71 m, stroke
      rate, glide periods, stroke acceleration patterns, body angle and work stroke(-1)
      were far more variable than during descent; however, mean speed remained fairly
      constant until buoyancy increased rapidly near the surface. For dives to depths
      >20 m, drag is by far the main component of mechanical work for these diving
      birds, and speed may be regulated to keep work against drag within a relatively
      narrow range.

PMID- 15579563
TI  - Sequence and expression of a constitutive, facilitated glucose transporter
      (GLUT1) in Atlantic cod Gadus morhua.
AB  - A putative glucose transporter, GLUT1, is reported for Atlantic cod Gadus morhua.
      A combination of RT-PCR, RLM-RACE and genome walking were used to articulate a
      4560 bp cDNA (GenBank accession number AY526497). It contains a 149 bp 5' UTR, a
      1470 bp open reading frame and a 2941 bp 3' UTR. At the nucleotide level, the cod
      GLUT1 ORF shares 78.2% sequence identity to human GLUT1 and the deduced amino
      acid sequence clusters with GLUT1s from rainbow trout and carp. GLUT1 transcript
      is highly expressed in brain, gill, heart and kidney and expressed to a lower
      level in at least six other tissues. Expression is evident immediately upon
      fertilization of eggs. Six hours of hypoxia at 40% DO(2) did not alter expression
      levels in brain, gill, heart or kidney. The level of expression is not
      substantially altered in heart during low temperature challenge, although there
      is a suggestion that colder temperature could lead to lower levels of expression,
      consistent with the concept that the cold-acclimated heart has a reduced
      dependence upon glucose as a metabolic fuel. Two months of starvation did not
      significantly alter the level of expression of GLUT1 in heart. This is in marked
      contrast to the rat heart where fasting leads to a substantial decrease in GLUT1
      levels. Overall, there is a ubiquitous tissue distribution of GLUT1, consistent
      with other species, and the level of gene expression, especially in heart, is
      relatively constant over a range of physiological conditions.

PMID- 15579564
TI  - The fluid dynamics of flight control by kinematic phase lag variation between two
      robotic insect wings.
AB  - Insects flying with two pairs of wings must contend with the forewing wake
      passing over the beating hindwing. Some four-winged insects, such as dragonflies,
      move each wing independently and therefore may alter the relative timing between
      the fore- and hindwing stroke cycles. The significance of modifying the phase
      relationship between fore- and hindwing stroke kinematics on total lift
      production is difficult to assess in the flying animal because the effect of wing
      wake interference critically depends on the complex wake pattern produced by the
      two beating wings. Here we investigate the effect of changing the fore- and
      hindwing stroke-phase relationship during hovering flight conditions on the
      aerodynamic performance of each flapping wing by using a dynamically scaled
      electromechanical insect model. By varying the relative phase difference between
      fore- and hindwing stroke cycles we found that the performance of the forewing
      remains approximately constant, while hindwing lift production may vary by a
      factor of two. Hindwing lift modulation appears to be due to two different fluid
      dynamic phenomenons: leading edge vortex destruction and changes in strength and
      orientation of the local flow vector. Unexpectedly, the hindwing regains
      aerodynamic performance near to that of the wing free from forewing wake
      interference, when the motion of the hindwing leads the forewing by around a
      quarter of the stroke cycle. This kinematic relationship between hind- and
      forewing closely matches the phase-shift commonly used by locusts and some
      dragonflies in climbing and forward flight. The experiments support previous
      assumptions that active neuromuscular control of fore- and hindwing stroke phase
      might enable dragonflies and other functionally four-winged insects to manipulate
      ipsilateral flight force production without further changes in wing beat
      kinematics.

PMID- 15579565
TI  - The tube cement of Phragmatopoma californica: a solid foam.
AB  - Phragmatopoma californica is a marine polychaete that builds protective tubes by
      joining bits of shell and sand grains with a secreted proteinaceous cement. The
      cement forms a solid foam (closed cells) via covalent crosslinking, as revealed
      by electron and laser scanning confocal microscopy. The cement contains
      extractable calcium and magnesium, and non-extractable phosphorus. Amino acid
      analysis demonstrated that the phosphorus is in the form of phosphoserine and
      that >90% of serine in the cement (i.e. 28 mol% of residues) is phosphorylated.
      In addition to previously identified basic proteins, the cement contains a highly
      acidic polyphosphoserine protein as a major component. We propose a model for the
      structure and bonding mechanism of the cement that has the following major
      features: (1) within the secretory pathway of cement gland cells, the
      electrostatic association of the oppositely charged proteins and divalent cations
      (Ca2+ and Mg2+) condense the cement proteins into dehydrated secretory granules;
      (2) the condensation of the cement leads to the separation of the solution into
      two aqueous phases (complex coacervation) that creates the closed cell foam
      structure of the cement; (3) rehydration of the condensed cement granules after
      deposition onto tube particles contributes to the displacement of water from the
      mineral substrate to facilitate underwater adhesion; and (4) after secretion,
      covalent cross-linking through oxidative coupling of DOPA gradually solidifies
      the continuous phase of the cement to set the porous structure.

PMID- 15579566
TI  - Role of nitric oxide in tolerance to lipopolysaccharide in mice.
AB  - The injection of repeated doses of lipopolysaccharide (LPS) results in
      attenuation of the febrile response, which is called endotoxin tolerance. We
      tested the hypothesis that nitric oxide (NO) arising from inducible NO synthase
      (iNOS) plays a role in endotoxin tolerance, using not only pharmacological trials
      but also genetically engineered mice. Body core temperature was measured by
      biotelemetry in mice treated with NG-monomethyl-L-arginine (L-NMMA, 40 mg/kg; a
      nonselective NO synthase inhibitor) or aminoguanidine (AG, 10 mg/kg; a selective
      iNOS inhibitor) and in mice deficient in the iNOS gene (iNOS KO) mice. Tolerance
      to LPS was induced by means of three consecutive LPS (100 microg/kg)
      intraperitoneal injections at 24-h intervals. In wild-type mice, we observed a
      significant reduction of the febrile response to repeated administration of LPS.
      Injection of L-NMMA and AG markedly enhanced the febrile response to LPS in
      tolerant animals. Conversely, iNOS-KO mice repeatedly injected with LPS did not
      become tolerant to the pyrogenic effect of LPS. These data are consistent with
      the notion that NO modulates LPS tolerance in mice and that iNOS isoform is
      involved in NO synthesis during LPS tolerance.

PMID- 15579567
TI  - Oxygen distribution in murine tumors: characterization using oxygen-dependent
      quenching of phosphorescence.
AB  - In the present work, a novel method for detecting hypoxia in tumors,
      phosphorescence quenching, was used to evaluate tissue and tumor oxygenation.
      This technique is based on the concept that phosphorescence lifetime and
      intensity are inversely proportional to the oxygen concentration in the tissue
      sample. We used the phosphor Oxyphor G2 to evaluate the oxygen profiles in three
      murine tumor models: K1735 malignant melanoma, RENCA renal cell carcinoma, and
      Lewis lung carcinoma. Oxygen measurements were obtained both as histograms of
      oxygen distribution within the sample and as an average oxygen pressure within
      the tissue sampled; the latter allowing real-time oxygen monitoring. Each of the
      tumor types examined had a characteristic and consistent oxygen profile. K1735
      tumors were all well oxygenated, with a peak oxygen pressure of 37.8 +/- 5.1
      Torr; RENCA tumors had intermediate oxygen pressures, with a peak oxygen pressure
      of 24.8 +/- 17.9 Torr; and LLC tumors were all severely hypoxic, with a peak
      oxygen pressure of 1.8 +/- 1.1 Torr. These results correlated well with
      measurements of tumor cell oxygenation measured by nitroimidazole (EF5) binding
      and were consistent with assessments of tumor blood flow by contrast enhanced
      ultrasound and tumor histology. The results show that phosphorescence quenching
      is a reliable, reproducible, and noninvasive method capable of providing real
      time determination of oxygen concentrations within tumors.

PMID- 15579568
TI  - Dynamic response characteristics of local muscle blood flow regulatory mechanisms
      in human forearm exercise.
AB  - We sought to understand the nature of control mechanisms involved in the
      adaptation of exercising muscle hyperemia. Seven subjects performed rhythmic
      dynamic forearm exercise under two exercise conditions: small step 1 [step
      increase from rest to 40% peak forearm vascular conductance (FVC), in ml.min(
      1).100 mmHg-1] for 5 min followed by small step 2 (further increase to 80% peak
      FVC for 5 min), and large step (step increase from rest to 80% peak FVC for 5
      min). FVC data were fit with a two- (small step 1) and three-component (small
      step 2, large step) exponential as appropriate. For the rapid phase I response,
      FVC dynamic response characteristics (time delay, time constant) were not
      affected by the magnitude of the work intensity increase when the transition
      began from rest, but were slower in the 40-80% transition. Rest-80% gain was
      greater than either rest-40% or 40-80% transitions but represented the same
      proportion of the phase I + phase II gain across all transitions (57 vs. 56 vs.
      57%, respectively, P = 0.975). For the slower phase II response, dynamic response
      characteristics were not affected by the magnitude of the work intensity increase
      when initiated from rest. The time constant was not altered when the transition
      began from exercise vs. rest. We conclude that 1) dynamic response
      characteristics of exercise hyperemia control mechanisms are not affected by the
      magnitude of work rate increase when forearm exercise is initiated from rest, 2)
      phase I but not phase II dynamic response characteristics are sensitive to
      baseline exercise intensity, and 3) the mechanisms contributing to phase I result
      in the same relative response magnitude, regardless of the size of the step
      increase in exercise intensity or the baseline from which it is initiated.

PMID- 15579569
TI  - Optimal oxygen pressure and time for reduced bubble formation in the N2-saturated
      decompressed prawn.
AB  - Bubbles that grow during decompression are believed to originate from preexisting
      gas micronuclei. We showed that pretreatment of prawns with 203 kPa oxygen before
      nitrogen loading reduced the number of bubbles that evolved on decompression,
      presumably owing to the alteration or elimination of gas micronuclei (Arieli Y,
      Arieli R, and Marx A. J Appl Physiol 92: 2596-2599, 2002). The present study
      examines the optimal pretreatment for this assumed crushing of gas micronuclei.
      Transparent prawns were subjected to various exposure times (0, 5, 10, 15, and 20
      min) at an oxygen pressure of 203 kPa and to 5 min at different oxygen pressures
      (PO2 values of 101, 151, 203, 405, 608, and 810 kPa), before nitrogen loading at
      203 kPa followed by explosive decompression. After the decompression, bubble
      density and total gas volume were measured with a light microscope equipped with
      a video camera. Five minutes at a PO2 of 405 kPa yielded maximal reduction of
      bubble density and total gas volume by 52 and 71%, respectively. It has been
      reported that 2-3 h of hyperbaric oxygen at bottom pressure was required to
      protect saturation divers decompressed on oxygen against decompression sickness.
      If there is a shorter pretreatment that is applicable to humans, this will be of
      great advantage in diving and escape from submarines.

PMID- 15579570
TI  - Prior heavy-intensity exercise speeds VO2 kinetics during moderate-intensity
      exercise in young adults.
AB  - The effect of prior heavy-intensity warm-up exercise on subsequent moderate
      intensity phase 2 pulmonary O2 uptake kinetics (tauVO2) was examined in young
      adults exhibiting relatively fast (FK; tauVO2 < 30 s; n = 6) and slow (SK; tauVO2
      > 30 s; n = 6) VO2 kinetics in moderate-intensity exercise without prior warm up.
      Subjects performed four repetitions of a moderate (Mod1)-heavy-moderate (Mod2)
      protocol on a cycle ergometer with work rates corresponding to 80% estimated
      lactate threshold (moderate intensity) and 50% difference between lactate
      threshold and peak VO2 (heavy intensity); each transition lasted 6 min, and each
      was preceded by 6 min of cycling at 20 W. VO2 and heart rate (HR) were measured
      breath-by-breath and beat-by-beat, respectively; concentration changes of muscle
      deoxyhemoglobin (HHb), oxyhemoglobin, and total hemoglobin were measured by near
      infrared spectroscopy (Hamamatsu NIRO 300). tauVO2 was lower (P < 0.05) in Mod2
      than in Mod1 in both FK (20 +/- 5 s vs. 26 +/- 5 s, respectively) and SK (30 +/-
      8 s vs. 45 +/- 11 s, respectively); linear regression analysis showed a greater
      "speeding" of VO2 kinetics in subjects exhibiting a greater Mod1 tauVO2. HR,
      oxyhemoglobin, and total hemoglobin were elevated (P < 0.05) in Mod2 compared
      with Mod1. The delay before the increase in HHb was reduced (P <0.05) in Mod2,
      whereas the HHb mean response time was reduced (P <0.05) in FK (Mod2, 22 +/- 3 s;
      Mod1, 32 +/- 11 s) but not different in SK (Mod2, 36 +/- 13 s; Mod1, 34 +/- 15
      s). We conclude that improved muscle perfusion in Mod2 may have contributed to
      the faster adaptation of VO2, especially in SK; however, a possible role for
      metabolic inertia in some subjects cannot be overlooked.

PMID- 15579571
TI  - Carotid body denervation alters ventilatory responses to ibotenic acid injections
      or focal acidosis in the medullary raphe.
AB  - Our aim was to determine the effects of carotid body denervation (CBD) on the
      ventilatory responses to focal acidosis and ibotenic acid (IA) injections into
      the medullary raphe area of awake, adult goats. Multiple microtubules were
      chronically implanted into the midline raphe area nuclei either before or after
      CBD. For up to 15 days after bilateral CBD, arterial PCO2 (PaCO2) (13.3 +/- 1.9
      Torr) was increased (P < 0.001), and CO2 sensitivity (-53.0 +/- 6.4%) was
      decreased (P <0.001). Thereafter, resting PaCO2 and CO2 sensitivity returned (P
      <0.01) toward control, but PaCO2 remained elevated (4.8 +/- 1.9 Torr) and CO2
      sensitivity reduced (-24.7 +/- 6.0%) > or =40 days after CBD. Focal acidosis (FA)
      at multiple medullary raphe area sites 23-44 days post-CBD with 50 or 80% CO(2)
      increased inspiratory flow (Vi), tidal volume (Vt), metabolic rate (VO2), and
      heart rate (HR) (P <0.05). The effects of FA with 50% CO2 after CBD did not
      differ from intact goats. However, CBD attenuated (P <0.05) the increase in Vi,
      Vt, and HR with 80% CO2, but it had no effect on the increase in VO2. Rostral but
      not caudal raphe area IA injections increased Vi, BP, and HR (P < 0.05), and
      these responses were accentuated (P <0.001) after CBD. CO2 sensitivity was
      attenuated (-20%; P <0.05) <7 days after IA injection, but thereafter it returned
      to prelesion values in CBD goats. We conclude the following: 1) the attenuated
      response to FA after CBD provides further evidence that the carotid bodies
      provide a tonic facilitory input into respiratory control centers, 2) the
      plasticity after CBD is not due to increased raphe chemoreceptor sensitivity, and
      3) the "error-sensing" function of the carotid body blunts the effect of strong
      stimulation of the raphe.

PMID- 15579572
TI  - Noradrenergic modulation of XII motoneuron inspiratory activity does not involve
      alpha2-receptor inhibition of the Ih current or presynaptic glutamate release.
AB  - Norepinephrine has powerful and diverse modulatory effects on hypoglossal (XII)
      motoneuron activity, which is important in maintaining airway patency. The
      objective was to test two hypotheses that alpha2-adrenoceptor-mediated,
      presynaptic inhibition of glutamatergic inspiratory drive (Selvaratnam SR, Parkis
      MA, and Funk GD. Brain Res 805: 104-115, 1998) and postsynaptic inhibition of the
      hyperpolarization-activated inward current (Ih) (Parkis MA and Berger AJ. Brain
      Res 769: 108-118, 1997) modulate XII inspiratory activity. Nerve and whole cell
      recordings were applied to rhythmic medullary slice preparations from neonatal
      rats (postnatal days 0-4) to monitor XII inspiratory burst amplitude and
      motoneuron properties. Application of an alpha2-receptor agonist (clonidine, 1
      mM) to the XII nucleus reduced inspiratory burst amplitude to 71 +/- 3% of
      control but had no effect on inspiratory synaptic currents. It also reduced the
      Ih current by approximately 40%, but an Ih current blocker (ZD7288), at
      concentrations that blocked approximately 80% of Ih, had no effect on inspiratory
      burst amplitude. The clonidine inhibition was unaffected by the GABAA antagonist
      (+)bicuculline but attenuated by the alpha2-antagonist rauwolscine and the
      imidazoline 1 (I1) antagonist efaroxan. The I1 agonist rilmenidine, but not the
      alpha2-agonist UK14304, inhibited XII output. Clonidine also reduced action
      potential amplitude or impaired repetitive firing. Although a contribution from
      alpha2, and in particular I1, receptors remains possible, results demonstrate
      that 1) noradrenergic modulation of XII inspiratory activity is unlikely to
      involve alpha2-receptor-mediated presynaptic inhibition of glutamate release or
      modulation of Ih; 2) inhibition of repetitive firing is a major factor underlying
      the inhibition of XII output by clonidine; and 3) Ih is present in neonatal XII
      motoneurons but does not contribute to shaping their inspiratory activity.

PMID- 15579573
TI  - In vivo alpha-adrenergic responses and troponin I phosphorylation: anesthesia
      interactions.
AB  - The mechanisms by which alpha-adrenergic stimulation of the heart in vivo can
      cause contractile dysfunction are not well understood. We hypothesized that alpha
      adrenergic-mediated contractile dysfunction is mediated through protein kinase C
      phosphorylation of troponin I, which in in vitro experiments has been shown to
      reduce actomyosin Mg-ATPase activity. We studied pressure-volume loops in
      transgenic mice expressing mutant troponin I lacking protein kinase C
      phosphorylation sites and hypothesized altered responses to phenylephrine. As
      anesthesia agents can produce markedly different effects on contractility, we
      studied two agents: avertin and alpha-chloralose-urethane. With alpha-chloralose
      urethane, at baseline, there were no contractile abnormalities in the troponin I
      mutants. Phenylephrine produced a 50% reduction in end-systolic elastance in wild
      type controls, although a 9% increase in troponin I mutants (P <0.05). Avertin
      was associated with reduced contractility compared with alpha-chloralose
      urethane. Avertin anesthesia, at baseline, produced a reduction in end-systolic
      elastance by 31% in the troponin I mutants compared with wild-type (P <0.05), and
      this resulted in further marked systolic and diastolic dysfunction with
      phenylephrine in the troponin I mutants. Dobutamine produced no significant
      difference in the contractile phenotype of the transgenic mice with either
      anesthetic regimen. In conclusion, these data (alpha-chloralose-urethane)
      demonstrate that alpha-adrenergic-mediated force reduction is mediated through
      troponin I protein kinase C phosphorylation. beta-Adrenergic responses are not
      mediated through this pathway. Altering the myofilament force-calcium
      relationship may result in in vivo increased sensitivity to negative inotropy.
      Thus choice of a negative inotropic anesthetic agent (avertin) with phenylephrine
      can lead to profound contractile dysfunction.

PMID- 15579574
TI  - Increased relaxation of immature airways to beta2-adrenoceptor agonists is
      related to attenuated expression of postjunctional smooth muscle muscarinic M2
      receptors.
AB  - Spontaneous or agonist-induced contraction of airway smooth muscle can be
      observed very early in fetal life, thus explaining the possible occurrence of
      bronchospasm in very low birth weight infants within the first days of life. In
      an attempt to better manage such bronchospasms, the aim of the present study was
      to investigate the age-specific modifications in airway smooth muscle relaxation
      to beta2-agonists and muscarinic antagonists using a combination of functional
      and molecular techniques. In the rat, isometric relaxation to the beta2-agonist
      salbutamol was examined in tracheae; we also examined muscarinic receptor
      expression (M2R and M3R mRNA levels) in airway smooth muscle by immunochemistry,
      Western blotting, and real-time PCR. Compared with adults, salbutamol-induced
      relaxation was twofold greater in immature rat isolated tracheae preconstricted
      by carbachol. This effect was associated with a lower expression of M2R in the
      smooth muscle of immature animals (sixfold and almost twofold as assessed by
      immunochemistry and Western blotting, respectively). Real-time PCR data indicate
      that changes in M2R expression according to age occurred at a posttranscriptional
      level. In adult airways, there was a significantly greater functional efficacy of
      M2R blockade by methoctramine compared with that shown in immature rats. Because
      of the limited availability of human neonate lung tissue, only the molecular part
      of the study was performed, and we observed a qualitatively similar effect, i.e.,
      a lower M2R expression in the neonatal airway smooth muscle, although this was
      quantitatively smaller. We conclude that beta2-agonist-induced relaxation is
      enhanced in immature compared with adult airways as a result of greater
      postjunctional M2R expression in adult airway smooth muscle. This finding may be
      of importance in the clinical management of bronchoconstriction in neonates.

PMID- 15579575
TI  - Effect of antioxidant vitamin treatment on the time course of hematological and
      hemorheological alterations after an exhausting exercise episode in human
      subjects.
AB  - This study examined the effects of a 2-mo antioxidant vitamin treatment on acute
      hematological and hemorheological alterations induced by exhausting exercise;
      both sedentary and trained individuals were employed. Eighteen young male, human
      subjects (9 sedentary, 9 trained by regular exercise) participated in the study
      and performed an initial maximal aerobic cycle ergometer exercise with frequent
      blood sampling over a 24-h period and analysis of hematological and
      hemorheological parameters. All subjects were treated with an antioxidant vitamin
      A, C, and E regimen, supplemented orally for 2 mo, and then subjected to a second
      exercise test and blood sampling at the end of this period. In the sedentary
      group during the first testing period (before vitamin treatment), white blood
      cell counts and granulocyte percentages were increased at 2 h after the exercise
      test and remained elevated for 4-12 h. Red blood cell (RBC) deformability and
      aggregation were also altered by exercise in the sedentary group before vitamin
      treatment. However, none of these parameters in the sedentary group were altered
      by exercise after the 2-mo period of antioxidant vitamin treatment. With the
      exception of a transient rise in granulocyte percentage, these parameters were
      also not affected in the trained subjects before the vitamin treatment.
      Significant increases of RBC lipid peroxidation observed 12 h after the exercise
      test in both sedentary and trained subjects were also totally prevented by
      vitamin treatment. Our results indicate that antioxidant vitamin treatment is
      effective in preventing the inflammation-like response and coincident adverse
      hemorheological changes after an episode of exhausting exercise, and suggest that
      such changes may be related to exercise-induced death events.

PMID- 15579576
TI  - Reproducibility of the cold-induced vasodilation response in the human finger.
AB  - Cold-induced vasodilation (CIVD) is a cyclic oscillation in blood flow that
      occurs in the extremities on cold exposure and that is likely associated with
      reduced risk of cold injury (e.g., frostbite) as well as improved manual
      dexterity and less pain while working in the cold. The CIVD response varies
      between individuals, but the within-subject reproducibility has not been
      adequately described. The purpose of this study was to quantify the within
      subject variability in the CIVD response under standardized conditions. Twenty
      one volunteers resting in a controlled environment (27 degrees C) immersed the
      middle finger in warm water (42 degrees C) for 15 min to standardize initial
      finger temperature and then in cold water (4 degrees C; CWI) for 30 min, on five
      separate occasions. Skin temperature (Tf) and blood flow (laser-Doppler;
      expressed as percent change from warm-water peak) responses that describe CIVD
      were identified, including initial nadir reached during CWI, onset time of CIVD,
      initial apex during CIVD, time of that apex, and overall mean during CWI. Within
      subject coefficient of variation for Tf across the five tests for the nail bed
      and pad, respectively, were as follows: nadir, 9 and 21%; onset, 18 and 19%;
      apex, 12 and 17%; apex time, 23 and 24%; mean 10 and 15%. For blood flow, these
      values were as follows: nadir 52 and 64%; onset, 6 and 5%; apex, 33 and 31%; apex
      time 9 and 8%; and mean 43 and 34%. Greater variability was found in the
      temperature response of the finger pad than the nail bed, but for blood flow the
      variability was similar between locations. Variability in onset and apex time
      between sites was similar for both temperature and blood flow responses. The
      reproducibility of the time course of CIVD suggests this methodology may be of
      value for further studies examining the mechanism of the response.

PMID- 15579577
TI  - Influence of brain angiotensin on thermoregulation and hydromineral balance
      during pregnancy in rats.
AB  - During mammalian pregnancy, body temperature decreases and there are changes in
      fluid and electrolyte balance. Angiotensin signaling mechanisms in the brain have
      been shown to influence thermoregulation and body fluid balance in the
      nonpregnant state. We hypothesized that brain angiotensin is also implicated in
      adjusting these physiological systems in the pregnant rat. We compared core
      temperature and fluid regulation in three groups of pregnant rats: untreated
      rats, rats receiving continuous infusion of an AT(1) antagonist candesartan (5
      microg.kg(-1).day(-1)) into a lateral cerebral ventricle to block brain AT(1)
      receptors, and rats receiving vehicle [artificial cerebrospinal fluid (aCSF)]
      vehicle. Untreated and aCSF-treated rats showed a decrease in colonic temperature
      (-0.5 and -0.8 degrees C respectively) by day 20 of gestation. However, rats
      treated with candesartan had increased colonic temperature compared with baseline
      (+0.9 degrees C), and their temperature was significantly higher on days 7 (P <
      0.05), 17 (P < 0.05), and 20 (P < 0.001) compared with the other groups (aCSF and
      untreated). Daily food and water intakes and body weight were not different
      between the three groups. Similarly, litter sizes and pup weights were equal in
      all groups. Finally, the expected decreases in plasma Na(+) and osmolality during
      pregnancy were equivalent in all groups. This study suggests that brain
      angiotensin mediates the progressive decrease in body temperature that occurs
      during pregnancy. However, the changes in fluid balance associated with pregnancy
      are not dependent on brain angiotensin.

PMID- 15579578
TI  - Occlusion of the upper airway does not augment the cardiovascular response to
      arousal from sleep in humans.
AB  - The cardiovascular response to an arousal from sleep at the termination of an
      obstructive apnea is more than double that to a spontaneous arousal. We
      investigated the hypothesis that stimulation of respiratory mechanoreceptors, by
      inspiring against an occluded airway during an arousal from sleep, augments the
      accompanying cardiovascular response. Arousals (>10 s) from stage 2 sleep were
      induced by a 1-s auditory tone (85 dB) during a concomitant 1-s inspiratory
      occlusion (O) and without an occlusion [i.e., control arousal (C)] in 15 healthy
      men (mean +/- SE: age, 25 +/- 1 yr). Arousals were associated with a significant
      increase in mean arterial blood pressure (MAP) at 4 s (P < 0.001) and a
      significant decrease in R-R interval at 3 s (P < 0.001). However, the magnitude
      of the cardiovascular response was not different during C compared with O (MAP:
      C, 86 +/- 3 to 104 +/- 3 mmHg; O, 86 +/- 3 to 105 +/- 3 mmHg; P = 0.99. R-R
      interval: C, 1.12 +/- 0.03 to 0.89 +/- 0.04 s; O, 1.11 +/- 0.02 to 0.87 +/- 0.02
      s, P = 0.99). Ventilation significantly increased during arousals under both
      conditions at the second breath (P < 0.001); this increase was not different
      between the two conditions (C: 4.40 +/- 0.29 to 6.76 +/- 0.61 l/min, O: 4.35 +/-
      0.34 to 7.65 +/- 0.73 l/min; P = 0.31). We conclude that stimulation of the
      respiratory mechanoreceptors by transient upper airway occlusion is unlikely to
      interact with the arousal-related autonomic outflow to augment the cardiovascular
      response in healthy young men.

PMID- 15579579
TI  - Mean body temperature does not modulate eccrine sweat rate during upright tilt.
AB  - Conflicting reports exist about the role of baroreflexes in efferent control of
      eccrine sweat rate. These conflicting reports may be due to differing mean body
      temperatures between studies. The purpose of this project was to test the
      hypothesis that mean body temperature modulates the effect of head-up tilt on
      sweat rate and skin sympathetic nerve activity (SSNA). To address this question,
      mean body temperature (0.9.internal temperature + 0.1.mean skin temperature),
      SSNA (microneurography of peroneal nerve, n = 8), and sweat rate (from an area
      innervated by the peroneal nerve and from two forearm sites, one perfused with
      neostigmine to augment sweating at lower mean body temperatures and the second
      with the vehicle, n = 12) were measured in 13 subjects during multiple 30 degrees
      head-up tilts during whole body heating. At the end of the heat stress, mean body
      temperature (36.8 +/- 0.1 to 38.0 +/- 0.1 degrees C) and sweat rate at all sites
      were significantly elevated. No significant correlations were observed between
      mean body temperature and the change in SSNA during head-up tilt (r = 0.07; P =
      0.62), sweating within the innervated area (r = 0.06; P = 0.56), sweating at the
      neostigmine treated site (r = 0.04; P = 0.69), or sweating at the control site (r
      = 0.01; P = 0.94). Also, for each tilt throughout the heat stress, there were no
      significant differences in sweat rate (final tilt sweat rates were 0.69 +/- 0.11
      and 0.68 +/- 0.11 mg.cm(-2).min(-1) within the innervated area; 1.04 +/- 0.16 and
      1.06 +/- 0.16 mg.cm(-2).min(-1) at the neostigmine-treated site; and 0.85 +/-
      0.15 and 0.85 +/- 0.15 mg.cm(-2).min(-1) at the control site, for supine and
      tilt, respectively). Hence, these data indicate that mean body temperature does
      not modulate eccrine sweat rate during baroreceptor unloading induced via 30
      degrees head-up tilt.

PMID- 15579580
TI  - Effect of phosphorylation by AMP-activated protein kinase on palmitoyl-CoA
      inhibition of skeletal muscle acetyl-CoA carboxylase.
AB  - AMP-activated protein kinase (AMPK) has previously been demonstrated to
      phosphorylate and inactivate skeletal muscle acetyl-CoA carboxylase (ACC), the
      enzyme responsible for synthesis of malonyl-CoA, an inhibitor of carnitine
      palmitoyltransferase 1 and fatty acid oxidation. Contraction-induced activation
      of AMPK with subsequent phosphorylation/inactivation of ACC has been postulated
      to be responsible in part for the increase in fatty acid oxidation that occurs in
      muscle during exercise. These studies were designed to answer the question: Does
      phosphorylation of ACC by AMPK make palmitoyl-CoA a more effective inhibitor of
      ACC? Purified rat muscle ACC was subjected to phosphorylation by AMPK. Activity
      was determined on nonphosphorylated and phosphorylated ACC preparations at acetyl
      CoA concentrations ranging from 2 to 500 microM and at palmitoyl-CoA
      concentrations ranging from 0 to 100 microM. Phosphorylation resulted in a
      significant decline in the substrate saturation curve at all palmitoyl-CoA
      concentrations. The inhibitor constant for palmitoyl-CoA inhibition of ACC was
      reduced from 1.7 +/- 0.25 to 0.85 +/- 0.13 microM as a consequence of
      phosphorylation. At 0.5 mM citrate, ACC activity was reduced to 13% of control
      values in response to the combination of phosphorylation and 10 muM palmitoyl
      CoA. Skeletal muscle ACC is more potently inhibited by palmitoyl-CoA after having
      been phosphorylated by AMPK. This may contribute to low-muscle malonyl-CoA values
      and increasing fatty acid oxidation rates during long-term exercise when plasma
      fatty acid concentrations are elevated.

PMID- 15579581
TI  - Difference in aftereffects following prolonged Achilles tendon vibration on
      muscle activity during maximal voluntary contraction among plantar flexor
      synergists.
AB  - It has been suggested that a suppression of maximal voluntary contraction (MVC)
      induced by prolonged vibration is due to an attenuation of Ia afferent activity.
      The purpose of the present study was to test the hypothesis that aftereffects
      following prolonged vibration on muscle activity during MVC differ among plantar
      flexor synergists owing to a supposed difference in muscle fiber composition. The
      plantar flexion MVC torque and surface electromyogram (EMG) of the medial head of
      gastrocnemius (MG), the lateral head of gastrocnemius (LG), and the soleus (Sol)
      were recorded in 13 subjects before and after prolonged vibration applied to the
      Achilles tendon at 100 Hz for 30 min. The maximal H reflexes and M waves were
      also determined from the three muscles, and the ratio between H reflexes and M
      waves (H/Mmax) was calculated before and after the vibration. The MVC torque was
      decreased by 16.6 +/- 3.7% after the vibration (P < 0.05; ANOVA). The H/Mmax also
      decreased for all three muscles, indicating that Ia afferent activity was
      successfully attenuated by the vibration in all plantar flexors. However, a
      reduction of EMG during MVC was observed only in MG (12.7 +/- 4.0%) and LG (11.4
      +/- 3.9%) (P < 0.05; ANOVA), not in Sol (3.4 +/- 3.0%). These results
      demonstrated that prolonged vibration-induced MVC suppression was attributable
      mainly to the reduction of muscle activity in MG and LG, both of which have a
      larger proportion of fast-twitch muscle fibers than Sol. This finding suggests
      that Ia-afferent activity that reinforces the recruitment of high-threshold motor
      units is necessary to enhance force exertion during MVC.

PMID- 15579582
TI  - Focus on implantation.

PMID- 15579583
TI  - Implantation mechanisms: insights from the sheep.
AB  - Implantation in all mammals involves shedding of the zona pellucida, followed by
      orientation, apposition, attachment and adhesion of the blastocyst to the
      endometrium. Endometrial invasion does not occur in domestic ruminants; thus,
      definitive implantation is achieved by adhesion of the mononuclear trophoblast
      cells to the endometrial lumenal epithelium (LE) and formation of syncytia by the
      fusion of trophoblast binucleate cells with the LE. This review highlights new
      information on mechanisms regulating the implantation cascade in sheep. The
      embryo enters the uterus on day 4 at the morula stage of development and then
      develops into a blastocyst by day 6. The blastocyst sheds the zona pellucida (day
      8), elongates to a filamentous form (days 11-16), and adheres to the endometrial
      LE (day 16). Between days 14 and 16, the binucleate cells begin to differentiate
      in the trophoblast and subsequently migrate and fuse with the endometrial LE to
      form syncytia. Continuous exposure of the endometrium to progesterone in early
      pregnancy downregulates the progesterone receptors in the epithelia, a process
      which is associated with loss of the cell-surface mucin MUC1 and induction of
      several secreted adhesion proteins. Recurrent early pregnancy loss in the uterine
      gland knockout ewe model indicates that secretions of the endometrial epithelia
      have a physiologic role in blastocyst elongation and implantation. A number of
      endometrial proteins have been identified as potential regulators of blastocyst
      development and implantation in sheep, including glycosylated cell adhesion
      molecule 1 (GlyCAM-1), galectin-15, integrins and osteopontin. The epithelial
      derived secreted adhesion proteins (GlyCAM-1, galectin-15 and osteopontin) are
      expressed in a dynamic temporal and spatial manner and regulated by progesterone
      and/or interferon tau, which is the pregnancy recognition signal produced by the
      trophoblast during blastocyst elongation. The noninvasive and protracted nature
      of implantation in domestic animals provides valuable opportunities to
      investigate fundamental processes of implantation that are shared among all
      mammals. Understanding of the cellular and molecular signals that regulate
      uterine receptivity and implantation can be used to diagnose and identify causes
      of recurrent pregnancy loss and to improve pregnancy outcome in domestic animals
      and humans.

PMID- 15579584
TI  - Embryonic diapause and its regulation.
AB  - Embryonic diapause, a condition of temporary suspension of development of the
      mammalian embryo, occurs due to suppression of cell proliferation at the
      blastocyst stage. It is an evolutionary strategy to ensure the survival of
      neonates. Obligate diapause occurs in every gestation of some species, while
      facultative diapause ensues in others, associated with metabolic stress, usually
      lactation. The onset, maintenance and escape from diapause are regulated by
      cascades of environmental, hypophyseal, ovarian and uterine mechanisms that vary
      among species and between the obligate and facultative condition. In the best
      known models, the rodents, the uterine environment maintains the embryo in
      diapause, while estrogens, in combination with growth factors, reinitiate
      development. Mitotic arrest in the mammalian embryo occurs at the G0 or G1 phase
      of the cell cycle, and may be due to expression of a specific cell cycle
      inhibitor. Regulation of proliferation in non- mammalian models of diapause
      provide clues to orthologous genes whose expression may regulate the reprise of
      proliferation in the mammalian context.

PMID- 15579585
TI  - Animal models of implantation.
AB  - Implantation is an intricately timed event necessary in the process of viviparous
      birth that allows mammals to nourish and protect their young during early
      development. Human implantation begins when the blastocyst both assumes a fixed
      position in the uterus and establishes a more intimate relationship with the
      endometrium. Due to the impracticalities of studying implantation in humans,
      animal models are necessary to decipher the molecular and mechanical events of
      this process. This review will discuss the differences in implantation between
      different animal models and describe how these differences can be utilized to
      investigate discrete implantation stages. In addition, factors that have been
      shown to be involved in implantation in the human and other various animal models
      including growth factors, cytokines, modulators of cell adhesion, and
      developmental factors will be discussed, and examples from each will be given.

PMID- 15579586
TI  - Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic activation of
      human oocytes.
AB  - At fertilization in mammals the sperm activates development of the oocyte by
      inducing a prolonged series of oscillations in the cytosolic free Ca2+
      concentration. One theory of signal transduction at fertilization suggests that
      the sperm cause the Ca2+ oscillations by introducing a protein factor into the
      oocyte after gamete membrane fusion. We recently identified this sperm-specific
      protein as phospholipase Czeta (PLCzeta), and we showed that PLCzeta triggers
      Ca2+ oscillations in unfertilized mouse oocytes. Here we report that
      microinjection of the complementary RNA for human PLCzeta causes prolonged Ca2+
      oscillations in aged human oocytes that had failed to fertilize during in vitro
      fertilization or intracytoplasmic sperm injection. The frequency of Ca2+
      oscillations was related to the concentration of complementary RNA injected. At
      low concentrations, PLCzeta stimulated parthenogenetic activation of oocytes.
      These embryos underwent cleavage divisions and some formed blastocysts. These
      data show that PLCzeta is a novel parthenogenetic stimulus for human oocytes and
      that it is unique in its ability to mimic the repetitive nature of the Ca2+
      stimulus provided by the sperm during human fertilization.

PMID- 15579587
TI  - DNA methylation pattern in human zygotes and developing embryos.
AB  - We report on observations of the global methylation/demethylation pattern of both
      pronuclei in human zygotes and in early embryos up to the blastocyst stage. Our
      results demonstrate that in about half of the zygotes examined the paternal
      chromatin was less methylated than the maternal chromatin. In the other half,
      both pronuclei exhibited the same intensity of labeling. The nuclei in developing
      embryos were intensively labeled for up to the four-cell stage; thereafter, a
      decline of labeling intensity was detected. Remethylation in some nuclei starts
      in late morulae. Surprisingly, and unlike the mouse, at the blastocyst stage the
      inner cell mass showed a weaker intensity of labeling than the trophectodermal
      cells.

PMID- 15579588
TI  - The protein encoded by cancer/testis gene D40/AF15q14 is localized in
      spermatocytes, acrosomes of spermatids and ejaculated spermatozoa.
AB  - We have previously identified and cloned a human gene, D40, that is
      preferentially expressed in testis among normal organs, while it is widely
      expressed in various human tumor cell lines and primary tumors derived from
      different organs. In this report, we have examined the expression and
      localization of this protein in human testis with an antibody specific to D40
      protein. In Western analyses, the anti-D40 antibody recognized a major band with
      a molecular mass of 300 kDa and a minor band of 250 kDa. These bands were not
      observed in the testis lysates from patients with Sertoli-cell-only syndrome and
      with Kleinfelter syndrome, who lack germ cells of the testis, indicating that D40
      protein is expressed in the germ cells of normal testis. Immunohistochemical
      studies have revealed that D40 protein is highly expressed in spermatocytes and
      in the pre-acrosome of round spermatids. In the acrosome, D40 protein expression
      is observed not inside but outside the acrosome membrane. This is consistent with
      the finding that the amino-acid sequence at the amino terminal of the D40 protein
      lacks a hydrophobic signal peptide that is required for proteins to translocate
      to the membrane. Expression of D40 protein is observed in the acrosome of
      ejaculated spermatozoa as well, although the level is low compared with that in
      the pre-acrosome of spermatids. These results suggest that D40 protein plays
      important roles in spermatogenesis, especially in the formation and maintenance
      of the acrosome.

PMID- 15579589
TI  - Exogenous interferon-gamma alters murine inner cell mass and trophoblast
      development. Effect on the expression of ErbB1, ErbB4 and heparan sulfate
      proteoglycan (perlecan).
AB  - Implantation is a crucial event in human pregnancy. The participation of
      cytokines in the implantation process has been widely documented, although the
      role of many of these molecules is still a matter of controversy. In a previous
      report from our laboratory, we demonstrated that addition of interferon-gamma to
      the culture medium produces deleterious effects on mouse embryo development. In
      this study we investigated the effect of this cytokine on outgrowing embryo
      morphology and on the expression of epidermal growth factor receptors (ErbBs) and
      heparan sulfate proteoglycan (perlecan) in mouse embryos cultured in vitro.
      Morphological assessment of inner cell mass and trophoblast development was
      carried on in-situ fixed and stained outgrowths. Localization of ErbB1, ErbB4 and
      perlecan on pre- and peri-implantation embryos was investigated by
      immunocytochemistry. Addition of interferon-gamma produced a deleterious effect
      on both inner cell mass and trophoblast morphology. Immunostaining demonstrated
      that ErbB1, ErbB4 and perlecan are present on pre-implantation embryos and
      blastocysts; interferon-gamma altered the expression of ErbB4 and Perlecan at the
      blastocyst stage. We propose that the effects produced by this cytokine could be
      related to the altered acquisition of adhesion competence and low implantation
      rates observed in certain reproductive immunological disorders.

PMID- 15579590
TI  - Available human feeder cells for the maintenance of human embryonic stem cells.
AB  - Mouse embryonic fibroblasts (MEFs) have been previously used as feeder cells to
      support the growth of human embryonic stem cells (hESCs). In this study, human
      adult uterine endometrial cells (hUECs), human adult breast parenchymal cells
      (hBPCs) and embryonic fibroblasts (hEFs) were tested as feeder cells for
      supporting the growth of hESCs to prevent the possibility of contamination from
      animal feeder cells. Cultured hUECs, hBPCs and hEFs were mitotically inactivated
      and then plated. hESCs (Miz-hES1, NIH registered) initially established on mouse
      feeder layers were transferred onto each human feeder layer and split every 5
      days. The morphology, expression of specific markers and differentiation capacity
      of hESCs adapted on each human feeder layer were examined. On hUEC, hBPC and hEF
      feeder layers, hESCs proliferated for more than 90, 50 and 80 passages
      respectively. Human feeder-based hESCs were positive for stage-specific embryonic
      antigen (SSEA)-3 and -4, and Apase; they also showed similar differentiation
      capacity to MEF-based hESCs, as assessed by the formation of teratomas and
      expression of tissue-specific markers. However, hESCs cultured on hUEC and hEF
      feeders were slightly thinner and flatter than MEF- or hBPC-based hESCs. Our
      results suggest that, like MEF feeder layers, human feeder layers can support the
      proliferation of hESCs without differentiation. Human feeder cells have the
      advantage of supporting more passages than when MEFs are used as feeder cells,
      because hESCs can be uniformly maintained in the undifferentiated stage until
      they pass through senescence. hESCs established and/or maintained under stable
      xeno-free culture conditions will be helpful to cell-based therapy.

PMID- 15579591
TI  - Contraception in mice immunized with recombinant zona pellucida subunit 3
      proteins correlates with Th2 responses and the levels of interleukin 4 expressed
      by CD4+ cells.
AB  - The immune responses and contraceptive effect in mice were tested following
      immunization with purified recombinant zona pellucida (ZP) proteins produced
      using a vaccinia (v) virus T7 mammalian expression system. Female BALB/c and CBA
      mice were immunized with recombinant mouse (m) ZP3 (vmZP3) or pig (p) ZPC (vpZPC)
      using Freund's adjuvants and boosted three times. Fertility and mean litter size
      were significantly reduced in groups of BALB/c mice immunized with recombinant
      vmZP3 and vpZPC compared with controls treated with Freund's adjuvants alone. In
      CBA mice, fertility and mean litter size were significantly reduced in groups of
      animals immunized with vmZP3 but not with vpZPC compared with the controls. Most
      infertile animals treated with vmZP3 and a single infertile BALB/c mouse treated
      with vpZPC lacked mature follicles in the ovaries, whilst no abnormalities were
      detected in the remaining vpZPC treated, fertile vmZP3 treated and control mice.
      All mice (both fertile and infertile) immunized with vmZP3 and vpZPC produced IgG
      antibodies, but the levels of total IgG, IgG1 and IgG2a did not correlate with
      infertility. All BALB/c and CBA mice immunized with vmZP3 and vpZPC showed
      greater delayed type hypersensitivity responses in the footpads after challenge
      with their respective antigens than controls, but these did not differ between
      the fertile and infertile mice. There was, however, a significant correlation
      between infertility and the levels of the Type 2 T helper cell (Th2) cytokine
      interleukin 4 produced by CD4+ cells from vmZP3 immunized mice in response to
      stimulation with vmZP3 and this did not apply to the levels of the Type 1 T
      helper cell (Th1) cytokine interferon gamma or the general proliferation
      response. The results support the conclusion that induction of Th2 responses in
      individual mice determines whether infertility develops in response to
      immunization with zona pellucida proteins.

PMID- 15579592
TI  - Ovarian follicular expression of mRNA encoding the type I IGF receptor and IGF
      binding protein-2 in sheep following five days of nutritional supplementation
      with glucose, glucosamine or lupins.
AB  - The IGF system is associated with ovarian folliculogenesis. The effect of the
      IGFs mediated through the type I receptor (IGF-IR) and IGF-binding protein-2
      (IGFBP-2), is to regulate the growth and atresia of follicles. To test if the
      mRNAs for IGF-IR and IGFBP-2 are differentially regulated in the follicle we used
      nutritional treatments that stimulate folliculogenesis and measured, by in situ
      hybridisation, their mRNAs expression. Groups of five anoestrous Merino ewes were
      fed wheat straw (control) or the control diet supplemented with lupins (500
      g/day). Other ewes were fed the control diet and infused with glucose (50 mmol/h)
      or with glucosamine (3.5 mmol/h). Intravaginal progestagen sponges were inserted
      for 12 days, and nutritional treatments were started 5 days before progestagen
      removal. Follicular development was studied after an artificial follicular phase,
      simulated by progestagen for 12 days and a regime of GnRH pulses given for 36 h
      following progestagen withdrawal, when the animals were killed. The ovaries were
      collected and stored at -80 degrees C until sectioning at 10 microm. Every 25
      28th and 29-32nd section was probed for IGF-IR and IGFBP-2 using 35S-labelled
      oligonucleotide probes. None of the nutritional treatments affected the number or
      size of follicles positive for IGF-IR, but glucose (P < 0.001) and lupin (P <
      0.001) treatments reduced the follicular concentration of mRNA. The nutritional
      treatments all increased the number of follicles positive for IGFBP-2 (P < 0.05)
      and reduced their mean diameter (P < 0.05) and with the exception of lupin
      feeding, the concentration of mRNA (P < 0.05). The results show that all
      treatments affected the intrafollicular IGF system and suggest that IGF-IR and
      IGFBP-2 are nutritionally regulated in the follicle. However, the effects of
      treatments were variable and suggest the existence of multiple regulatory
      mechanisms that allow for normal variation in composition and balance of the
      ruminant diet.

PMID- 15579593
TI  - Direct in vivo effects of leptin on ovarian steroidogenesis in sheep.
AB  - Leptin, the metabolic fat hormone, has been shown to have effects on reproduction
      in mice and to modulate steroid production by cultured ovarian somatic cells in a
      number of species. However, a direct role of leptin on normal ovarian function in
      vivo has not been shown. In this paper the effect of passive immunisation against
      leptin (experiment 1; 20 ml antiserum or non-immune plasma i.v.; n = 6/treatment)
      and direct ovarian infusion of leptin (experiment 2; 0, 2 or 20 mug recombinant
      ovine leptin; n = 4/treatment) during the early follicular phase was investigated
      in sheep with ovarian autotransplants, which allow recovery of ovarian venous
      blood and regular non-invasive scanning of the ovary. Passive immunisation
      against leptin resulted in an acute increase (P < 0.05) in ovarian oestradiol
      secretion but had no effect on gonadotrophin concentrations, ovulation or
      subsequent luteal function. Conversely, direct ovarian arterial infusion of the
      low dose of leptin resulted in an acute decline (P < 0.05) in ovarian oestradiol
      secretion whereas the high dose, which resulted in supra-physiological leptin
      concentrations, had no effect on oestradiol production compared with the
      controls. Neither dose of leptin had any effect on gonadotrophin concentrations
      or ovulation but both doses resulted in an increase (P < 0.05) in progesterone
      concentrations over the subsequent luteal phase. In conclusion, together these
      data provide strong in vivo evidence that leptin can modulate ovarian
      steroidogenesis directly and acutely in ruminants and suggest that leptin is an
      alternate regulatory system whereby nutritional status can regulate reproductive
      activity.

PMID- 15579594
TI  - Antioxidant enzymatic defence systems in sheep corpus luteum throughout
      pregnancy.
AB  - The activities of copper, zinc-superoxide dismutase (SOD1), manganese SOD (SOD2),
      glutathione peroxidase (GPX), glutathione reductase (GSSG-R) and glutathione S
      transferase (GST) were studied in sheep corpora lutea (CL) obtained on days 15,
      40, 60, 80 and 128 of pregnancy. Maintained enzymatic activity of SOD1, SOD2,
      GPX, GSSG-R and GST were found in the sheep CL throughout pregnancy. Enzymatic
      activity of SOD1, GPX and GST increased significantly from day 15 to day 40 of
      pregnancy, and thereafter remained constant until day 128. SOD2 and GSSG-R
      activities were not different between any days of pregnancy examined. Apoptotic
      luteal cells identified by the terminal deoxynucleotidyl transferase-mediated
      fluorescein-dUTP nick-end labelling were very rarely observed, and their
      incidence (less than 0.5%) was not different between days of pregnancy. These
      results showed that the activities of antioxidant enzymes in the sheep CL are
      subject to major changes during early pregnancy, suggesting that the CL of early
      pregnancy may be rescued from luteolysis through increasing activities of key
      antioxidant enzymes and inhibition of apoptosis. Maintained levels of antioxidant
      enzymes in the CL throughout pregnancy may be linked to reactive oxygen species
      continuously generated in the steroidogenically active luteal cells, and may be
      involved in the maintenance of luteal steroidogenic activity and cellular
      integrity.

PMID- 15579595
TI  - Cloning and expression of a novel CREB mRNA splice variant in human testis.
AB  - Identification of genes specifically expressed in adult and fetal testis is
      important in furthering our understanding of testis development and function. In
      this study, a novel human transcript, designated human testis cAMP-responsive
      element-binding protein (htCREB), was identified by hybridization of adult and
      fetal human testis cDNA probes with a human cDNA microarray containing 9216
      clones. The htCREB transcript (GenBank Accession no. AY347527) was expressed at
      2.35-fold higher levels in adult human testes than in fetal testes. Sequence and
      ntBLAST analyses against the human genome database indicated that htCREB was a
      novel splice variant of human CREB. RT-PCR-based tissue distribution experiments
      demonstrated that the htCREB transcript was highly expressed in adult human
      testis and in healthy sperm, but not in testes from patients with Sertoli cell
      only syndrome. Taken together, these results suggest that the htCREB transcript
      is chiefly expressed in germ cells and is most likely involved in
      spermatogenesis.

PMID- 15579596
TI  - Protein phosphatase-type 2B is involved in the regulation of the acrosome
      reaction but not in the temperature-dependent flagellar movement of fowl
      spermatozoa.
AB  - The motility and acrosomal integrity of fowl spermatozoa in TES/NaCl buffer, with
      or without homogenized inner perivitelline layers (IPVL) prepared from laid fowl
      eggs, was almost negligible at 40 degrees C. However, motility became vigorous
      even at 40 degrees C when 2 mmol CaCl2/l was added, and the acrosome reaction was
      also stimulated in the presence, but not in the absence, of IPVL. The presence of
      deltamethrin or fenvalerate, specific inhibitors of protein phosphatase-type 2B
      (PP2B), did not permit the restoration of motility at 40 degrees C but, in the
      presence of IPVL, these compounds stimulated the acrosome reaction in a dose
      dependent manner in the range of 1-1000 nmol/l. These results suggest that IPVL
      is necessary for the activation of the acrosome reaction in fowl spermatozoa and
      that Ca2+ plays an important role in the stimulation of motility and acrosomal
      exocytosis. Furthermore, it appears that the intracellular molecular mechanisms
      for the regulation of the acrosome reaction of fowl spermatozoa are different
      from those for the restoration of motility, i.e. protein dephosphorylation by
      PP2B in the former but not in the latter case.

PMID- 15579597
TI  - Reduction of the incidence of polyspermic penetration into porcine oocytes by
      pretreatment of fresh spermatozoa with adenosine and a transient co-incubation of
      the gametes with caffeine.
AB  - To reduce the incidence of polyspermic penetration, the effects of transient
      exposure of washed fresh spermatozoa to caffeine in a brief co-culture in vitro
      fertilization (IVF) system were examined. A pretreatment effect of spermatozoa
      with adenosine was also examined. When 5 mmol caffeine/l was supplemented during
      periods of co-culture and additional culture periods until 8 h after
      insemination, a shortened co-incubation period of gametes (30 denuded oocytes in
      100 microl modified Medium 199-suspended spermatozoa at 2.5 x10(5) sperm/ml) from
      30 to 5 min increased the monospermy rate in total mature oocytes examined. The
      number of spermatozoa binding to the zona surface was significantly lower in
      oocytes co-cultured for 5 min (33.1 +/- 2.2) than 8 h (207.6 +/- 13.7). A limited
      exposure of gametes to 5 mmol caffeine/l only during a transient co-culture
      period for 5 or 30 min significantly reduced the mean number of sperm cells that
      penetrated into the oocyte. Transient exposure of spermatozoa to caffeine for
      only 5 min increased the percentage of capacitated cells but not acrosome-reacted
      cells, as compared with a whole exposure treatment. Furthermore, preincubation of
      spermatozoa with 10 micromol adenosine/l for 90 min increased both the incidence
      of capacitated cells and the monospermy rate and consequently decreased the
      number of sperm cells that penetrated into the oocyte. In conclusion, these
      results have demonstrated that a new transient co-incubation IVF system, in which
      denuded oocytes are co-cultured with spermatozoa in medium containing caffeine
      for 5 to 30 min and then continuing the culture in caffeine-free medium, will
      reduce the incidence of polyspermic penetration. Preincubation of fresh
      spermatozoa with adenosine before the transient co-incubation IVF can also
      improve the monospermy rate. Furthermore, asynchrony in the morphology of sperm
      nuclei in polyspermic oocytes was reduced by the pretreatment with adenosine and
      a brief exposure to caffeine.

PMID- 15579598
TI  - Sperm distribution in the genital tract of the bitch following artificial
      insemination in relation to the time of ovulation.
AB  - In the present study, sperm distribution in the genital tract of the bitch
      following artificial insemination (AI) in relation to the time of ovulation was
      investigated by histology, scanning electron microscopy (SEM) and flushing. Ten
      bitches were inseminated intravaginally with 500 x 10(6) spermatozoa: three dogs
      before ovulation, four dogs during ovulation and three dogs after ovulation.
      Ovariohysterectomy was performed 24 h after AI. Half of the genital tract was
      divided into nine segments (cervix, corpus uteri, caudal, middle and cranial
      uterine horn (UTH), utero-tubal junction (UTJ), isthmus, ampulla and
      infundibulum), which were processed for histology and SEM. The contralateral UTH
      and uterine tube (UT) were flushed, and several sperm characteristics were
      assessed. Histology revealed that the spermatozoa were mainly located in the
      uterine glands and at the UTJ, while very few spermatozoa were detected in the
      UT. Insemination during ovulation resulted in higher percentages of glands with
      spermatozoa in the different parts of the uterus (P < 0.05). Evaluation by SEM
      showed higher numbers of spermatozoa in several parts of the uterus for bitches
      inseminated during ovulation (P < 0.05). The mean number of spermatozoa flushed
      from the UTH and the UT was low. No significant differences in the evaluated
      sperm quality parameters were found between the flushings of the UTH and the UT.
      In conclusion, based on our findings, the uterine glands and the UTJ might act as
      sperm reservoirs in the bitch and sperm transport in the genital tract is
      affected by the time of AI in relation to ovulation.

PMID- 15579599
TI  - Reducing agents induce microtubule extrusion in demembranated mammalian
      spermatozoa.
AB  - To understand the mechanism regulating flagellar bending in spermatozoa, it is
      important to investigate the regulation of microtubule sliding in the flagellar
      axoneme. It has been shown that protease treatment following demembranation with
      Triton X-100 disrupts the connections between microtubules and induces extrusion
      of microtubules from the flagellar axoneme. This approach enables a direct
      investigation of the regulation of microtubule sliding; however, the percentage
      of spermatozoa with protease-induced extrusion was relatively low, probably due
      to protease digestion of some regulatory motility proteins, as well as proteins
      connecting the microtubules. In this study, we demonstrate microtubule extrusion
      in most hamster and mouse demembranated spermatozoa upon treatment with a high
      concentration of the reducing agents dithiothreitol or 2-mercaptoethanol, without
      the use of proteases. The extrusion of microtubules occurred when the spermatozoa
      were treated with concentrations of the reducing agents that were sufficient for
      the reduction of the disulfide bonds of IgG. These results suggest that the
      arrangement of the axonemal structures connecting doublet microtubules depends to
      an important degree on -S-S- bonds. Close observation of the extrusion process
      using the present method revealed that microtubules were extruded on the same
      side as that of the curve of the sperm head, and also on the opposite side.
      Furthermore, we noted that extrusion always started on one side, followed by the
      other side, but was never initiated on both sides simultaneously.

PMID- 15579600
TI  - Spermatozoa motility in the Persian sturgeon, Acipenser persicus: effects of pH,
      dilution rate, ions and osmolality.
AB  - Sperm motility is a prerequisite factor determining semen quality and fertilizing
      capacity. The effects of environmental factors including pH, cations and
      osmolality as well as the role of dilution rate on sperm motility parameters in
      Acipenser persicus were studied. The best pH and dilution rate for activation of
      spermatozoa were pH 8.0 and dilution ratio 1:50. Ionic factors can stimulate the
      initiation of sperm activation. The maximum percentage of motile sperm and total
      duration of sperm motility were observed in solutions containing 25 mM NaCl, 0.2
      mM KCl, 3 mM CaSO4, 10 mM MgSO4 and sucrose with an osmolality of 50 mosmol kg(
      1). The present study provides us with some basic knowledge about sturgeon
      spermatozoa biosensitivity to ionic and osmolality effects. A sensitivity of A.
      persicus sperm was observed after induction of activation of sperm motility in
      solution containing cations or sucrose with high osmolality. Concentrations more
      than 50 mM Na+, more than 1 mM K+, more than 3 mM Ca2+ and more than 10 mM Mg2+
      had negative effects on sperm motility. Also, osmolality more than 100 mosmol kg(
      1) had an inhibitory effect. It is clear that ions and osmolality stimulate the
      motility of spermatozoa by changes in the properties of the plasma membrane
      including its potential and its ionic conductance. The inhibitory role of high
      osmolality of the swimming medium (more than 100 mosmol kg(-1)) and insufficient
      osmolality of the seminal plasma to inhibit semen motility suggested that
      osmolality is not the principal factor preventing sperm motility in seminal fluid
      but that K+ is a major inhibitory factor of sperm motility in seminal plasma.

PMID- 15579601
TI  - Functional significance of the cell volume for detecting sperm membrane changes
      and predicting freezability in dog semen.
AB  - Due to the similarity of plasma membrane changes induced by capacitation and
      cryopreservation, the parameters describing sperm response to capacitating
      conditions can be used for evaluating the cryopreservation response in many
      animal systems. In dog sperm, the response of the total sperm population to
      ionophore treatment has been shown to be an indication of the freezability of
      semen samples. Another sperm functional characteristic decisive for
      cryopreservability is cell volume regulation, due to the generation of essential
      osmotic gradients across the plasma membrane during the freeze-thaw cycles. In
      the present study, cryopreservation-induced changes in the membrane functional
      integrity were examined by monitoring the osmotically induced response of cell
      volume and the response to an ionophore in live cell populations. Cell volume
      measurements were performed on Percoll-washed suspensions of freshly diluted and
      frozen-thawed dog spermatozoa. The proportion of live acrosome-reacted cells was
      evaluated by flow cytometry after incubation under capacitating conditions in the
      presence of the calcium ionophore, A23187. During freezing-thawing, significant
      membrane changes occurred related to the disturbance of volume control ability
      and the loss of a proportion of live acrosome-reacted cells (P < 0.05). There
      were significant differences between individuals with respect to the degree of
      functional and structural membrane changes after thawing. Significant
      correlations were found between acrosomal integrity and functional membrane
      integrity. When assessed in freshly diluted semen, these parameters correlated
      with those of frozen-thawed semen samples, pointing to the similarities between
      mechanisms of cryopreservation-related changes and those mechanisms that mediate
      changes in membrane permeabilities and in cell volume regulation. The detection
      of changes in the sperm plasma membrane by monitoring the sperm cell volume
      represents a simple, rapid and sensitive method to estimate sperm quality after
      the cryopreservation procedure. The individual variability in response to osmotic
      stress or to calcium ionophore treatment appears to reflect the subtle
      differences in the sperm membrane functionality which are crucial for the
      prediction of cryopreservability.

PMID- 15579602
TI  - Follicular, endocrine and behavioural dynamics of the Indian rhinoceros
      (Rhinoceros unicornis) oestrous cycle.
AB  - Longitudinal ultrasound, behaviour and endocrine evaluations were conducted, over
      14 to 18 months, in two young female Indian rhinoceroses (Rhinoceros unicornis)
      to characterize the oestrous cycle. Both females showed the same pattern of
      follicular development producing a large follicle (10-12 cm diameter) on one of
      the ovaries that persisted for 8.5 +/- 4.68 days before spontaneously ovulating.
      Ovulation occurred in all eight cycles monitored in a 6- to 7-year-old female
      versus 10 out of 14 cycles monitored in a 5- to 6-year-old female. Ultrasound
      examinations confirmed follicular collapse 48 h following the onset of
      behavioural oestrus in ovulatory cycles, while anovulatory cycles were associated
      with the formation of a haemorrhagic follicle. The day of behavioural oestrus
      corresponded to peak urinary oestrogen conjugate concentrations for each cycle,
      but anovulatory cycles had lower concentrations on the day of behavioural oestrus
      compared with ovulatory cycles. A transient increase in urinary progesterone
      metabolite concentrations was detected 1 day prior to ovulation. Irregular
      urinary progesterone metabolite profiles followed anovulatory cycles, reflecting
      varying degrees of follicular luteinization. In an attempt to ensure that a cycle
      would result in ovulation in the 5- to 6-year-old female, a GnRH treatment was
      tested during two separate cycles. Administration of GnRH on the day of
      behavioural oestrus resulted in an increase in urinary luteinizing hormone
      concentrations 2 h following injection. Regardless, ovulation did not occur in
      response to treatment. This study provides the first ultrasound data on ovarian
      activity in the Indian rhinoceros and establishes normal physiologic and
      behavioural relationships during the oestrous cycle that may facilitate the
      breeding of this species in captivity.

PMID- 15579603
TI  - Short photoperiod inhibition of growth in body mass and reproduction in ACI, BUF,
      and PVG inbred rats.
AB  - Laboratory rats have been generally considered non-photoresponsive, but strains
      of laboratory rats have been found to be variable for this trait. Young males of
      both the Fischer (F344) and Brown Norway strains (BN) suppress reproductive
      development, food intake and body mass in short winter photoperiod (short days
      (SD); 8 h light:16 h darkness), and food restriction interacts with SD to enhance
      the effect of SD alone. Conversely, young male Harlan Sprague Dawley outbred
      rats, along with other outbred laboratory rats tested, have little or no response
      to SD except when unmasked by food restriction or other treatments, and have
      generally been considered nonphotoperiodic. In order to assess how widespread
      this trait might be among rat strains, and to test for uncoupling of reproductive
      and nonreproductive responses, we tested 3 additional inbred strains, including
      ACI, PVG and BUF rats, for photoresponsiveness and for unmasking of photoperiodic
      responses by food restriction. Young males of all three inbred strains exhibited
      photoresponsiveness in testis mass (5-20% lower in SD), seminal vesicle mass (20
      50% lower in SD), and body mass (5-10% lower in SD). Food restriction also
      suppressed reproduction, but there was little or no interaction with the effects
      of photoperiod. The results are consistent with the hypothesis that laboratory
      rats are genetically variable for photoperiodism, and that photoresponsiveness
      may be widespread among inbred rat strains, as all five inbred strains tested
      have shown photoperiodic responses. The results are particularly important
      because standard research protocols may unknowingly manipulate this pathway in
      rats, causing unsuspected variability among or within studies.

PMID- 15579606
TI  - Update on myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disorder caused by autoantibodies against the
      nicotinic acetylcholine receptor on the postsynaptic membrane at the
      neuromuscular junction and characterised by weakness and fatigability of the
      voluntary muscles. It has a bimodal peak of incidence with first peak in the
      third decade and the second peak in the sixth decade. It is probably
      underdiagnosed in the very old population. Our understanding of the pathogenesis,
      immunology, and molecular biology of myasthenia gravis has greatly improved in
      last three decades. It is almost always possible to establish the diagnosis of
      myasthenia gravis with the current tests. The modern treatment is highly
      successful and the mortality of treated myasthenia gravis is practically zero.
      However, there are still important gaps in our knowledge of the origin of
      myasthenia gravis, the factors that contribute to chronic disease, and the way to
      cure the disease. In this article the current knowledge of the various aspects of
      myasthenia gravis are outlined.

PMID- 15579605
TI  - Heart and mind: (1) relationship between cardiovascular and psychiatric
      conditions.
AB  - The relationship of our emotions and psyche to heart disease is intriguing. In
      this article we have reviewed the evidence linking cardiovascular and
      neuropsychiatric disorders and the possible mechanisms and pathophysiology of
      this association. This review is derived from Medline searches (1966-2002) using
      the relevant search terms (psychiatric disease, cardiovascular disease,
      depression, anxiety, and pathophysiology). Finally, the possible role of using
      mood enhancing therapies (mainly antidepressants) and their safety in patients
      with cardiovascular disorders is briefly discussed. In a companion paper, the
      therapeutic aspects of these two conditions is highlighted.

PMID- 15579608
TI  - Gastro-oesophageal reflux and bronchial asthma: current status and future
      directions.
AB  - In recent years there have been several reports suggesting an association between
      bronchial asthma and gastro-oesophageal reflux; however a cause and effect
      relationship has not been proven yet. Confirmation of such a relationship is
      likely to have far reaching implications on the management of asthma. Reliable
      assessment of this issue is hampered by the presence of various lacunae in most
      of the published studies. Hence it is essential to carefully examine the strength
      of data suggesting a link between asthma and reflux. This article critically
      analyses currently available literature on the subject (including published
      reviews, meta-analyses, and randomised clinical trials in the English language)
      and summarises valid conclusions that can be drawn; it also proposes a framework
      for future studies to resolve the issue.

PMID- 15579609
TI  - Healthcare reforms: implications for the education and training of acute and
      critical care nurses.
AB  - This paper offers a wide ranging analysis of the drivers that resulted in
      scrutiny of medical, nursing, and healthcare professional roles. It suggests that
      what is needed is a coherent vision of the future shape of the health workforce.
      This requires moving beyond the presumption that reforming working practices
      primarily involves "delegating doctors" responsibilities to nurses. The paper
      argues that it is self evident that the implications of changes in healthcare
      roles and the ability of existing professionals to function effectively in the
      future will require education, training, and human resource investment supportive
      of the changes. It suggests a clear definition of competence and a national
      standard to practice is essential for nurses working in acute and acute critical
      settings. There should therefore be a correlation between levels of practice,
      levels of education, and remuneration. Furthermore, education programmes for
      senior nurses should sit coherently alongside the education programmes required
      by Modernising Medical Careers. Finally, the realisation of the government's
      service and modernisation agenda will require a culture change within higher
      education institutions, postgraduate deaneries, professional organisations,
      workforce development confederations, and NHS trusts.

PMID- 15579610
TI  - Communication skills training in postgraduate medicine: the development of a new
      course.
AB  - It has long been accepted that communication is of central importance in
      healthcare, and a core aspect of clinical competence. Many educational
      institutions and Royal Colleges now reflect this and consider communication
      skills a priority in postgraduate examination. The new examination "Practical
      Assessment of Clinical and Examination Skills" has replaced the Royal College of
      Physicians MRCP part 2 clinical and oral examination. This examination now
      consists of five clinical stations, two of which focus on communication skills. A
      short course for postgraduate trainees has been designed to address the
      communication skills requirements of the part 2 clinical examination. The aims,
      development, and content of the course are described. Emphasis is placed on
      candidates practising skills with patients and receiving feedback during the
      course. Evidence suggests that practice with feedback is an essential ingredient
      of communication skills courses, and is more effective than other methods such as
      observing experts or video examples, or simply discussing issues in
      communication. Results of a preliminary evaluation indicate that the course was
      perceived as valuable by candidates and that the aims, format, and content were
      appropriate. Although the preliminary evaluation was largely positive, it could
      be argued that the acid test of the effectiveness of a course is an objective
      evaluation of skills, observed before and after the course, a development that is
      being considered for future evaluation of the course. Recommendations for
      applying this type of training to postgraduate trainees in any branch of medicine
      are given.

PMID- 15579611
TI  - Transfer of hospitals and "additional premises" to the state: questionable
      morality in the implementation of the National Health Service Act (1946).
AB  - The National Health Service Act of 1946, pioneered by Aneurin Bevan, came into
      being on the "appointed day", 5 July 1948. Hospitals with their "additional
      premises" throughout Britain were "seized" by the state and incorporated into
      this vast socialist enterprise. While the majority of the population welcomed
      this new initiative in the creation of a welfare state, associated with medical
      care from cradle to grave, not all (especially members of various Hospital Boards
      of Management) were so enthusiastic. The hospitals for "incurables" (long stay
      patients) were unhappy and lost a vast proportion of their income owing to a
      great deal of procrastination; but most of them ultimately managed to escape
      nationalisation after a prolonged period of negotiation, by a claim that they
      were "homes" rather than "hospitals". The confiscation of property which had been
      built as a result of voluntary subscription was another huge and highly
      contentious matter, which has been highlighted in recent years. The future of the
      Seamen's Hospital Society's properties represents a good example of this.

PMID- 15579612
TI  - Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo
      controlled trial.
AB  - BACKGROUND: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long
      duration of action. Its role in migraine has not been systematically evaluated.
      AIM: To study the efficacy of rofecoxib in migraine. METHOD: In a randomised
      placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were
      compared regarding their efficacy in relieving acute migraine attack. Migraine
      patients with 2-6 attacks per month were recruited. Headache severity, functional
      disability, and severity of associated symptoms were graded on a 0-3 scale. The
      primary endpoint was pain relief at two hours. Relief of associated symptoms and
      sustained pain relief for 24 hours were also noted. RESULT: One hundred and
      twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and
      placebo (42) groups. One hundred and one patients were followed up: 33 on
      rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16-62 (mean
      31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on
      rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated
      symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and
      9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on
      rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen
      group, five patients had abdominal pain but there were no side effects in those
      on rofecoxib or in the control group. Both rofecoxib and ibuprofen were
      significantly effective in relieving pain, associated symptoms at two hours, and
      in sustained pain relief. There was no significant difference between rofecoxib
      and ibuprofen in aborting acute migraine attacks. CONCLUSIONS: Both ibuprofen and
      rofecoxib were superior to placebo in aborting an acute migraine attack, and
      there was no significant difference in their efficacy in an acute migraine
      attack.

PMID- 15579613
TI  - Flecainide challenge test for the diagnosis of Brugada syndrome.

PMID- 15579614
TI  - Neurotological status in Behcet's disease and its ophthalmological correlates.
AB  - OBJECTIVE: To assess neurotological status and its ophthalmological correlates in
      Behcet's disease. STUDY DESIGN: A cross sectional study in which 17 patients with
      Behcet's disease and 13 healthy controls were included. PATIENTS AND METHODS: The
      patients were divided into two groups: those with and without end stage ocular
      involvement. Neurotological status was evaluated with audiological tests (pure
      tone and speech audiometry, tympanometry, short increment sensitivity index, tone
      decay, and evoked response audiometry), and Dix-Halpike positional testing.
      RESULTS: The positional test was normal. The audiological test results of the
      patients with and without end stage ocular involvement were not significantly
      different (p>0.05). A sloping audiogram with bilateral symmetric and mild
      sensorineural hearing loss was the main audiogram obtained. There was no
      relationship between the presence or absence of the end stage ocular involvement
      and the otological parameters studied excluding I-III interval on evoked response
      audiometry (p>0.05). CONCLUSION: Although the main underlying pathogenetic factor
      in Behcet's disease is the autoimmune vasculitis, the mechanisms involved in the
      pathogenesis of neurological and ocular damage may be different. Alternatively,
      the differential involvement of certain organ systems may not reflect the nature
      of the disease process itself, but rather the manner in which each organ responds
      to injury.

PMID- 15579615
TI  - Deep vein thrombosis after total hip and knee arthroplasty in Indian patients.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is one of the most common complications of
      total hip (THA) and total knee arthroplasty (TKA). Though the reported incidence
      of DVT is very high, that of proximal DVT is low and that of fatal
      thromboembolism is very low. Hence the issue of prophylaxis for DVT remains
      controversial. The incidence of DVT is based on various studies in European and
      American populations. The Asian population is genetically and socially quite
      different from American and European populations, and the incidence of DVT can be
      quite different. Therefore a prospective study was initiated at our centre to
      determine incidence of DVT after THA and TKA in Indian patients. METHODS: A
      prospective study was conducted on 60 hips in 45 patients and 46 knees in 26
      patients who underwent THA and TKA respectively, without any known risk factors
      for thromboembolic disease. DVT was studied by preoperative and postoperative
      serial colour Doppler ultrasonography. No prophylaxis was given to any of the
      patients. RESULTS: DVT was found in two patients who had undergone THA. No case
      of DVT was detected in any patient who had undergone TKA. CONCLUSION: These
      results suggest that the incidence of DVT in Indian patients is very low and is
      not comparable with American and European populations. It is therefore not cost
      effective to advise prophylaxis in Indian patients undergoing THA/TKA who have no
      known risk factors for DVT.

PMID- 15579616
TI  - Nodules of fibrocollagenous scar tissue induced by subcutaneous insulin
      injections: a cause of poor diabetic control.
AB  - A 46 year old man with longstanding type 1 diabetes developed major weight loss
      and marked deterioration in diabetic control. He had been persistently injecting
      insulin into areas of abdominal lipohypertrophy within which hard collagenised
      fibrous tissue nodules had developed. Injecting insulin at different sites
      dramatically improved blood glucose control. Fibrocollagenous nodules induced by
      insulin injections have not been previously described. Examination of a further
      73 type 1 patients revealed lipohypertrophy in 44% and hard subcutaneous nodules
      on two.

PMID- 15579617
TI  - Oesophageal haematoma and associated Mallory-Weiss tear.
AB  - Intramural oesophageal haematoma is a rare condition that may present as vomiting
      or haematemesis. Mallory-Weiss tear has been proposed as a possible aetiology but
      the evidence to support this is circumstantial. A case of oesophageal haematoma
      associated with evidence of Mallory-Weiss tear on endoscopy that helps to support
      this hypothesis is presented.

PMID- 15579618
TI  - Left over bowels: an unique complication in a surviving twin.
AB  - Conjoint twins have always been a surgical challenge. The authors report an
      unusual finding in a surviving epigastric heteropagus twin. A 17 year old boy who
      underwent laparotomy for acute intestinal obstruction revealed a blind ending but
      complete duplication of the large bowel and an accessory liver in the falciform
      ligament, along with a separate gall bladder but with fused bile ducts. The
      findings suggest that the duplicated bowel loop and the accessory liver were
      remnants of the incomplete parasite twin, assimilated into the body of the
      autosite, which remained asymptomatic for 17 years. This case is being reported
      because of the uniqueness of the finding.

PMID- 15579619
TI  - Eosinophilia and symptomatic pulmonary amyloidosis.
AB  - The case of a man with progressive breathlessness and pulmonary infiltration
      caused by AL amyloidosis associated with multiple myeloma is presented. There was
      a marked peripheral eosinophilia, which has not previously been described with
      amyloidosis.

PMID- 15579620
TI  - Pathological fracture in a pregnant woman.

PMID- 15579621
TI  - Testicular mass in a resting cell.

PMID- 15579622
TI  - A man with abdominal pain.

PMID- 15579623
TI  - Effects of transgene expression of superoxide dismutase and glutathione
      peroxidase on pulmonary epithelial cell growth in hyperoxia.
AB  - Prolonged exposure to supraphysiological oxygen concentrations results in the
      generation of reactive oxygen species, which can cause significant lung injury in
      critically ill patients. Supplementation with human recombinant antioxidant
      enzymes (AOE) may mitigate hyperoxic lung injury, but it is unclear which
      combination and concentration will optimally protect pulmonary epithelial cells.
      First, stable cell lines were generated in alveolar epithelial cells (MLE12)
      overexpressing one or more of the following AOE: Mn superoxide dismutase (MnSOD),
      CuZnSOD, or glutathione peroxidase 1. Next, A549 cells were transduced with 50
      300 particles/cell of recombinant adenovirus containing either LacZ or each of
      the three AOE (alone or in combination). Cells were then exposed to 95% O(2) for
      up to 3 days, with cell number and viability determined daily. Overexpression of
      either MnSOD (primarily mitochondrial) or CuZnSOD (primarily cytosolic) reversed
      the growth inhibitory effects of hyperoxia within the first 48 h of exposure,
      resulting in a significant increase in viable cells (P < 0.05), with 1.5- to 3
      fold increases in activity providing optimal protection. Protection from
      mitochondrial oxidation was confirmed by assessing aconitase activity, which was
      significantly improved in cells overexpressing MnSOD (P < 0.05). Data indicate
      that optimal protection from hyperoxic injury occurs in cells coexpressing MnSOD
      and glutathione peroxidase 1, with prevention of mitochondrial oxidation being a
      critical factor. This has important implications for clinical trials in preterm
      infants receiving SOD supplementation to prevent acute and chronic lung injury.

PMID- 15579624
TI  - Adrenomedullin expression in a rat model of acute lung injury induced by hypoxia
      and LPS.
AB  - Adrenomedullin (ADM) is upregulated independently by hypoxia and LPS, two key
      factors in the pathogenesis of acute lung injury (ALI). This study evaluates the
      expression of ADM in ALI using experimental models combining both stimuli: an in
      vivo model of rats treated with LPS and acute normobaric hypoxia (9% O2) and an
      in vitro model of rat lung cell lines cultured with LPS and exposed to hypoxia
      (1% O2). ADM expression was analyzed by in situ hybridization, Northern blot,
      Western blot, and RIA analyses. In the rat lung, combination of hypoxia and LPS
      treatments overcomes ADM induction occurring after each treatment alone. With in
      situ techniques, the synergistic effect of both stimuli mainly correlates with
      ADM expression in inflammatory cells within blood vessels and, to a lesser
      extent, to cells in the lung parenchyma and bronchiolar epithelial cells. In the
      in vitro model, hypoxia and hypoxia + LPS treatments caused a similar strong
      induction of ADM expression and secretion in epithelial and endothelial cell
      lines. In alveolar macrophages, however, LPS-induced ADM expression and secretion
      were further increased by the concomitant exposure to hypoxia, thus paralleling
      the in vivo response. In conclusion, ADM expression is highly induced in a
      variety of key lung cell types in this rat model of ALI by combination of hypoxia
      and LPS, suggesting an essential role for this mediator in this syndrome.

PMID- 15579625
TI  - Pulmonary hypertension impairs alveolarization and reduces lung growth in the
      ovine fetus.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is a clinical disorder
      characterized by abnormal vascular structure, growth, and reactivity. Disruption
      of vascular growth during early postnatal lung development impairs
      alveolarization, and newborns with lung hypoplasia often have severe pulmonary
      hypertension. To determine whether pulmonary hypertension can directly impair
      vascular growth and alveolarization in the fetus, we studied the effects of
      chronic intrauterine pulmonary hypertension on lung growth in fetal lambs. We
      performed surgery, which included partial constriction of the ductus arteriosus
      (DA) to induce pulmonary hypertension (PH, n = 14) or sham surgery (controls, n =
      13) in fetal lambs at 112-125 days (term = 147 days). Tissues were harvested near
      term for measurement of right ventricular hypertrophy (RVH), radial alveolar
      counts (RAC), mean linear intercepts (MLI), wall thickness, and vessel density of
      small pulmonary arteries. Chronic DA constriction caused RVH (P < 0.0001),
      increased wall thickness of small pulmonary arteries (P < 0.002), and reduced
      small pulmonary artery density (P < 0.005). PH also reduced alveolarization,
      causing a 27% reduction in RAC and 20% increase in MLI. Furthermore, prolonged DA
      constriction (21 days) not only decreased RAC and increased MLI by 30% but also
      caused a 25% reduction of lung-body weight ratio. We conclude that chronic PH
      reduces pulmonary arterial growth, decreases alveolar complexity, and impairs
      lung growth. We speculate that chronic hypertension impairs vascular growth,
      which disrupts critical signaling pathways regulating lung vascular and alveolar
      development, thereby interfering with alveolarization and ultimately resulting in
      lung hypoplasia.

PMID- 15579626
TI  - In vivo inosine protects alveolar epithelial type 2 cells against hyperoxia
      induced DNA damage through MAP kinase signaling.
AB  - Inosine, a naturally occurring purine with anti-inflammatory properties, was
      assessed as a possible modulator of hyperoxic damage to the pulmonary alveolar
      epithelium. Rats were treated with inosine, 200 mg/kg ip, twice daily during 48-h
      exposure to >90% oxygen. The alveolar epithelial type 2 cells (AEC2) were then
      isolated and cultured. AEC2 isolated from inosine-treated hyperoxic rats had less
      DNA damage and had increased antioxidant status compared with AEC2 from hyperoxic
      rats. Inosine treatment during hyperoxia also reduced the proportion of AEC2 in S
      and G2/M phases of the cell cycle and increased levels of the DNA repair enzyme 8
      oxoguanine DNA glycosylase. Bronchoalveolar lavage (BAL) recovered from
      hyperoxic, inosine-treated rats contained threefold higher levels of active
      transforming growth factor-beta than BAL from rats exposed to hyperoxia alone,
      and Smad2 was activated in AEC2 isolated from these animals. ERK1/2 was activated
      both in freshly isolated and 24-h-cultured AEC2 by in vivo inosine treatment,
      whereas blockade of the MAPK pathway in vitro reduced the protective effect of in
      the vivo inosine treatment. Together, the data suggest that inosine treatment
      during hyperoxic exposure results in protective signaling mediated through
      pathways downstream of MEK. Thus inosine may deserve further evaluation for its
      potential to reduce hyperoxic damage to the pulmonary alveolar epithelium.

PMID- 15579627
TI  - The murine SP-C promoter directs type II cell-specific expression in transgenic
      mice.
AB  - Genomic DNA from the mouse pulmonary surfactant protein C (SP-C) gene was
      analyzed in transgenic mice to identify DNA essential for alveolar type II cell
      specific expression. SP-C promoter constructs extending either 13 or 4.8 kb
      upstream of the transcription start site directed lung-specific expression of the
      bacterial chloramphenicol acetyl transferase (CAT) reporter gene. In situ
      hybridization analysis demonstrated alveolar cell-specific expression in the
      lungs of adult transgenic mice, and the pattern of 4.8 SP-C-CAT expression during
      development paralleled that of the endogenous SP-C gene. With the use of deletion
      constructs, lung-specific, low-level CAT activity was detected in tissue assays
      of SP-C-CAT transgenic mice retaining 318 bp of the promoter. In transient and
      stable cell transfection experiments, the 4.8-kb SP-C promoter was 90-fold more
      active as a stably integrated gene. These findings indicate that 1) the 4.8-kb SP
      C promoter is sufficient to direct cell-specific and developmental expression, 2)
      an enhancer essential for lung-specific expression maps to the proximal 318-bp
      promoter, and 3) the activity of the 4.8-kb SP-C promoter construct is highly
      dependent on its chromatin environment.

PMID- 15579628
TI  - Defect of hepatocyte growth factor production by fibroblasts in human pulmonary
      emphysema.
AB  - Pulmonary emphysema results from an excessive degradation of lung parenchyma
      associated with a failure of alveolar repair. Secretion by pulmonary fibroblasts
      of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) is crucial
      to an effective epithelial repair after lung injury. We hypothesized that
      abnormal HGF or KGF secretion by pulmonary fibroblasts could play a role in the
      development of emphysema. We measured in vitro production of HGF and KGF by human
      fibroblasts cultured from emphysematous and normal lung samples. HGF and KGF
      production was quantified at basal state and after stimulation. Intracellular
      content of HGF was lower in emphysema (1.52 pg/mug, range of 0.15-7.40 pg/mug)
      than in control fibroblasts (14.16 pg/mug, range of 2.50-47.62 pg/mug; P =
      0.047). HGF production by emphysema fibroblasts (19.3 pg/mug protein, range of
      10.4-39.2 pg/mug) was lower than that of controls at baseline (57.5 pg/mug, range
      of 20.4-116 pg/mug; P = 0.019) and after stimulation with interleukin-1beta or
      prostaglandin E(2). Neither retinoic acids (all-trans and 9-cis) nor N
      acetylcysteine could reverse this abnormality. KGF production by emphysema
      fibroblasts (5.3 pg/mug, range of 2.2-9.3 pg/mug) was similar to that of controls
      at baseline (2.6 pg/mug, range of 1-6.1 pg/mug; P = 0.14) but could not be
      stimulated with interleukin-1beta. A decreased secretion of HGF by pulmonary
      fibroblasts could contribute to the insufficient alveolar repair in pulmonary
      emphysema.

PMID- 15579629
TI  - Anti-inflammatory response is associated with mortality and severity of infection
      in sepsis.
AB  - Using a murine model of sepsis, we found that the balance of tissue pro- to anti
      inflammatory cytokines directly correlated with severity of infection and
      mortality. Sepsis was induced in C57BL/6 mice by cecal ligation and puncture
      (CLP). Liver tissue was analyzed for levels of IL-1beta, IL-1 receptor antagonist
      (IL-1ra), tumor necrosis factor (TNF)-alpha, and soluble TNF receptor 1 by ELISA.
      Bacterial DNA was measured using quantitative real-time PCR. After CLP, early
      predominance of proinflammatory cytokines (6 h) transitioned to anti-inflammatory
      predominance at 24 h. The elevated anti-inflammatory cytokines were mirrored by
      increased tissue bacterial levels. The degree of anti-inflammatory response
      compared with proinflammatory response correlated with the bacterial
      concentration. To modulate the timing of the anti-inflammatory response, mice
      were treated with IL-1ra before CLP. This resulted in decreased proinflammatory
      cytokines, earlier bacterial load, and increased mortality. These studies show
      that the initial tissue proinflammatory response to sepsis is followed by an anti
      inflammatory response. The anti-inflammatory phase is associated with increased
      bacterial load and mortality. These data suggest that it is the timing and
      magnitude of the anti-inflammatory response that predicts severity of infection
      in a murine model of sepsis.

PMID- 15579630
TI  - Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic
      allergic airway inflammation.
AB  - In the present study we evaluated the role of neurokinins in the modulation of
      inducible nitric oxide synthase (iNOS) inflammatory cell expression in guinea
      pigs with chronic allergic airway inflammation. In addition, we studied the acute
      effects of nitric oxide inhibition on this response. Animals were anesthetized
      and pretreated with capsaicin (50 mg/kg sc) or vehicle 10 days before receiving
      aerosolized ovalbumin or normal saline twice weekly for 4 wk. Animals were then
      anesthetized, mechanically ventilated, given normal saline or N(G)-nitro-l
      arginine methyl ester (l-NAME, 50 mg/kg ic), and challenged with ovalbumin.
      Prechallenge exhaled NO increased in ovalbumin-exposed guinea pigs (P < 0.05
      compared with controls), and capsaicin reduced this response (P < 0.001).
      Compared with animals inhaled with normal saline, ovalbumin-exposed animals
      presented increases in respiratory system resistance and elastance and numbers of
      total mononuclear cells and eosinophils, including those expressing iNOS (P <
      0.001). Capsaicin reduced all these responses (P < 0.05) except for iNOS
      expression in eosinophils. Treatment with l-NAME increased postantigen challenge
      elastance and restored both resistance and elastance previously attenuated by
      capsaicin treatment. Isolated l-NAME administration also reduced total
      eosinophils and mononuclear cells, as well as those cells expressing iNOS (P <
      0.05 compared with ovalbumin alone). Because l-NAME treatment restored lung
      mechanical alterations previously attenuated by capsaicin, NO and neurokinins may
      interact in controlling airway tone. In this experimental model, NO and
      neurokinins modulate eosinophil and lymphocyte infiltration in the airways.

PMID- 15579631
TI  - Surfactant protein D influences surfactant ultrastructure and uptake by alveolar
      type II cells.
AB  - Surfactant protein D (SP-D) is a member of the collectin family of the innate
      host defense proteins. In the lung, SP-D is expressed primarily by type II cells.
      Gene-targeted SP-D-deficient [SP-D(-/-)] mice have three- to fivefold higher
      surfactant lipid pool sizes. However, surfactant synthesis and secretion by type
      II cells and catabolism by alveolar macrophages are normal in SP-D(-/-) mice.
      Therefore, we hypothesized that SP-D might regulate surfactant homeostasis by
      influencing surfactant structure, thereby altering its uptake by type II cells.
      Large (LA) and small aggregate (SA) surfactant were isolated from bronchoalveolar
      lavage fluid (BALF) from SP-D(-/-), wild-type [SP-D(+/+)], and transgenic mice in
      which SP-D was expressed under conditional control of doxycycline in alveolar
      type II cells. Uptake of both LA and SA isolated from SP-D(-/-) mice by normal
      type II cells was decreased. Abnormally dense lipid forms were observed by
      electron microscopy of LA from SP-D(-/-) mice. SA from SP-D(-/-) mice consisted
      of atypical multilamellated small vesicles. Abnormalities in surfactant uptake by
      type II cells and in surfactant ultrastructure were corrected by conditional
      expression of SP-D in vivo. Preincubation of BALF from SP-D(-/-) mice with SP-D
      changed surfactant ultrastructure to be similar to that of SP-D(+/+) mice in
      vitro. The rapid changes in surfactant structure, increased uptake by type II
      cells, and decreased pool sizes normally occurring in the postnatal period were
      not seen in SP-D(-/-) mice. SP-D regulates uptake and catabolism by type II cells
      and influences the ultrastructure of surfactant in the alveolus.

PMID- 15579633
TI  - CXCR4-transgene expression significantly improves marrow engraftment of cultured
      hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex
      vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12)
      correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow
      engraftment. We demonstrate that mobilized human CD34+ peripheral blood stem
      cells (CD34+ PBSCs) lose CXCR4 expression during prolonged culture. We transduced
      CD34+ PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more
      CXCR4 expression in over 87% of CD34+ cells. CXCR4-transduced cells yielded
      increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six
      day cultured CXCR4-transduced cells demonstrated significant engraftment in
      nonobese diabetic/severe combined immunodeficient mice under conditions in which
      control transduced cells resulted in low or no engraftment. We conclude that
      transduction-mediated overexpression of CXCR4 significantly improves marrow
      engraftment of cultured PBSCs.

PMID- 15579634
TI  - In vitro cultured islet-derived progenitor cells of human origin express human
      albumin in severe combined immunodeficiency mouse liver in vivo.
AB  - Studies in rodents suggest the presence of a hepatopancreatic stem cell in adult
      pancreas that may give rise to liver cells in vivo. The aim of the present study
      was to determine the ability of human islet-derived cells to adopt a hepatic
      phenotype in vivo. Cultured human islet-derived progenitor cells that did not
      express albumin in vitro were stained with the red fluorescent dye PKH26 and
      injected into the liver of severe combined immunodeficiency mice. After 3 or 12
      weeks, red fluorescent cells were detected in 11 of 15 livers and were mostly
      single cells that were well integrated into the liver tissue. Human albumin was
      found in 8 of 11 animals by immunohistochemistry, and human albumin mRNA was
      detected in 4 of 10 host livers. The mechanism underlying this phenomenon seems
      to be transdifferentiation, because human and mouse albumin were found to be
      expressed in distinct cells in the host liver.

PMID- 15579635
TI  - Phenotypic characterization of murine primitive hematopoietic progenitor cells
      isolated on basis of aldehyde dehydrogenase activity.
AB  - There are several different technical approaches to the isolation of
      hematopoietic stem cells (HSCs) with long-term repopulating ability, but these
      have problems in terms of yield, complexity, or cell viability. Simpler
      strategies for HSC isolation are needed. We have enriched primitive hematopoietic
      progenitors from murine bone marrow of mice from different genetic backgrounds by
      lineage depletion followed by selection of cells with high aldehyde dehydrogenase
      activity using the Aldefluor reagent (BD Biosciences, Oxford, U.K.). Lin-
      ALDH(bright) cells comprised 26.8 +/- 1.0% of the total Lin- population of C57BL6
      mice, and 23.5 +/- 1.0% of the Lin- population of BALB/c mice expressed certain
      cell-surface markers typical of primitive hematopoietic progenitors. In vitro
      hematopoietic progenitor function was substantially higher in the Lin-
      ALDH(bright) population compared with the Lin- ALDH(low) cells. These cells have
      higher telomerase activity and the lowest percentage of cells in S phase. These
      data strongly suggest that progenitor enrichment from Lin- cells on the basis of
      ALDH is a valid method whose simplicity of application makes it advantageous over
      conventional separations.

PMID- 15579636
TI  - Directing stem cell differentiation into the chondrogenic lineage in vitro.
AB  - A major area in regenerative medicine is the application of stem cells in
      cartilage tissue engineering and reconstructive surgery. This requires well
      defined and efficient protocols for directing the differentiation of stem cells
      into the chondrogenic lineage, followed by their selective purification and
      proliferation in vitro. The development of such protocols would reduce the
      likelihood of spontaneous differentiation of stem cells into divergent lineages
      upon transplantation, as well as reduce the risk of teratoma formation in the
      case of embryonic stem cells. Additionally, such protocols could provide useful
      in vitro models for studying chondrogenesis and cartilaginous tissue biology. The
      development of pharmacokinetic and cytotoxicity/genotoxicity screening tests for
      cartilage-related biomaterials and drugs could also utilize protocols developed
      for the chondrogenic differentiation of stem cells. Hence, this review critically
      examines the various strategies that could be used to direct the differentiation
      of stem cells into the chondrogenic lineage in vitro.

PMID- 15579637
TI  - Technical assessment of the first 20 years of research using mouse embryonic stem
      cell lines.
AB  - This review assesses the effect that mouse embryonic stem (ES) cells have had on
      biomedical research during the 20 years that followed their isolation in 1981.
      Notable scientific discoveries enabled by these cell lines--including insights
      into cell cycle regulation, spatial and temporal relationships during
      development, and the roles of transcription factors and homeobox genes in
      developmental pathways--are discussed. The acceleration of basic discovery of
      gene function and the genetic basis of disease using a breakthrough technology
      (homologous recombination between modified gene constructs and the ES cell
      genome) became the principal enabling method to establish transgenic laboratory
      animals with single targeted genetic change. This review also examines the
      widespread influence of mouse ES cells as an enabling technology by highlighting
      their effect on drug development paradigms, directed differentiation to treat
      specific diseases, nuclear transfer protocols used in cloning, and establishment
      of methodologies for isolating non-rodent ES cells. This review concludes with a
      brief analysis of the most influential mouse ES cell lines of the first 20 years
      as viewed within the twin contexts of human disease application and contributions
      to the primary literature.

PMID- 15579638
TI  - Stem cell assays: something old, something new, something borrowed.
AB  - Numerous assays exist that measure the function of stem cells. In this article,
      we review in detail the history and future of existing stem cell assays.
      Hematopoietic stem cells (HSCs) are historically the most well studied, but new
      developments in stem cell research, including the claim of stem cell plasticity,
      have caused controversies related to technical issues, as well as to semantics.
      Stem cell research requires proper definitions, and utilization of stem cell
      assays, especially since research on non-HSCs that lack solid stem cell assays,
      is rapidly evolving. These emerging fields may benefit from what has been learned
      from HSC assays: most important, that the true potential of stem cells can only
      be assessed retrospectively. This also relates to new developments in HSC
      research, when limiting numbers of in vitro-manipulated stem cells are
      transplanted. The most conflicting results arise when cells express stem cell
      characteristics in one assay but not in another. Should we adjust our definition
      of a stem cell? If so, when do we decide a claim of stem cell activity to be
      justified? We therefore recommend using multiple stem cell assays, preferably at
      least one in vivo assay. These assays should measure functionality of the
      putative stem cell population.

PMID- 15579639
TI  - Enforced activation of STAT5A facilitates the generation of embryonic stem
      derived hematopoietic stem cells that contribute to hematopoiesis in vivo.
AB  - Little is known about the molecular mechanisms that direct the transition from
      primitive to definitive hematopoiesis. In this study, we cocultured murine
      embryonic stem (ES) cells on OP9 stroma to induce hematopoietic differentiation
      as a model to study factors involved in the generation of adult hematopoietic
      stem cells (HSCs). Overexpression of the constitutively activated mutant signal
      transducer and activator of transcription (STAT) 5A(1*6) in ES cells facilitated
      the generation of cells that expressed the endothelial-hemangioblast marker Flk-1
      within 5 days of coculture on OP9. The first CD41+/ CD45+/c-Kit+/(Flk-1)-
      hematopoietic cells arose in our culture conditions between days 5 and 7.
      Persistent activation of STAT5A greatly enhanced the generation of hematopoietic
      progenitors compared with controls, as determined by colony assays in
      methylcellulose. Moreover, whereas controls generated only a short transient wave
      of hematopoiesis lasting less than 3 weeks, expression of STAT5A(1*6) resulted in
      the generation of hematopoietic cobblestone area-forming cells (CAFCs) on OP9
      that could be serially passaged onto new OP9, giving rise to second and third
      CAFCs that generated hematopoietic progenitors for > or = 5 weeks, indicating a
      role for STAT5A in HSC self-renewal in vitro. Several definitive hematopoietic
      genes were upregulated by STAT5A (1*6), as well as Runx1/AML1, vascular
      endothelial growth factor, oncostatin M receptor, HoxB4, Wnt5A, Delta-like-1, and
      Bmi-1. Furthermore, ES-derived hematopoietic cells expressing STAT5A(1*6)
      contributed to myeloid-lymphoid hematopoiesis in primary and secondary nonobese
      diabetic-severe combined immunodeficiency recipients, although no donor-derived
      cells could be detected after 7 weeks in the secondary recipients. These data
      indicate that a persistent activation of STAT5A allows the generation of ES
      derived HSCs that can, at least for an intermediate period, contribute to
      hematopoiesis in vivo.

PMID- 15579640
TI  - Committing embryonic stem cells to early endocrine pancreas in vitro.
AB  - A panel of genetic markers was used to assess the in vitro commitment of murine
      embryonic stem (ES) cells toward the endoderm-derived pancreas and to distinguish
      insulin-expressing cells of this lineage from other lineages such as neuron,
      liver, and yolk sac. There are two nonallelic insulin genes in mice. Neuronal
      cells express only insulin II, whereas the pancreas expresses both insulin I and
      II. Yolk sac and fetal liver express predominately insulin II, small amounts of
      insulin I, and no glucagon. We found that ES-derived embryoid bodies cultured in
      the presence of stage-specific concentrations of monothio-glycerol and 15% fetal
      calf serum, followed by serum-free conditions, give rise to a population that
      expresses insulin I, insulin II, pdx-1 (a pancreas marker), and Sox17 (an
      endoderm marker). Immunohistochemical staining shows intracellular insulin
      particles, and its de novo production was confirmed by staining for C-peptide.
      Most, but not all, of the insulin+ or C-peptide+ cells coexpress glucagon,
      demonstrating a differentiation pathway to pancreas rather than yolk sac or fetal
      liver. Addition of beta-cell specification and differentiation factors activin
      beta B, nicotinamide, and exendin-4 to later-stage culture increased insulin
      positive cells to 2.73% of the total population, compared with the control
      culture, which gave rise to less than 1% insulin-staining cells. These findings
      suggest that stepwise culture manipulations can direct ES cells to become early
      endocrine pancreas.

PMID- 15579641
TI  - Differentiation of human embryonic stem cells to dopaminergic neurons in serum
      free suspension culture.
AB  - The use of human embryonic stem cells (hESCs) as a source of dopaminergic neurons
      for Parkinson's disease cell therapy will require the development of simple and
      reliable cell differentiation protocols. The use of cell cocultures, added
      extracellular signaling factors, or transgenic approaches to drive hESC
      differentiation could lead to additional regulatory as well as cell production
      delays for these therapies. Because the neuronal cell lineage seems to require
      limited or no signaling for its formation, we tested the ability of hESCs to
      differentiate to form dopamine-producing neurons in a simple serum-free
      suspension culture system. BG01 and BG03 hESCs were differentiated as suspension
      aggregates, and neural progenitors and neurons were detectable after 2-4 weeks.
      Plated neurons responded appropriately to electrophysiological cues. This
      differentiation was inhibited by early exposure to bone morphogenic protein (BMP)
      4, but a pulse of BMP-4 from days 5 to 9 caused induction of peripheral neuronal
      differentiation. Real-time polymerase chain reaction and whole-mount
      immunocytochemistry demonstrated the expression of multiple markers of the
      midbrain dopaminergic phenotype in serum-free differentiations. Neurons
      expressing tyrosine hydroxylase (TH) were killed by 6-hydroxydopamine (6-OHDA), a
      neurotoxic catecholamine. Upon plating, these cells released dopamine and other
      catecholamines in response to K+ depolarization. Surviving TH+ neurons, derived
      from the cells differentiated in serum-free suspension cultures, were detected 8
      weeks after transplantation into 6-OHDA-lesioned rat brains. This work suggests
      that hESCs can differentiate in simple serum-free suspension cultures to produce
      the large number of cells required for transplantation studies.

PMID- 15579642
TI  - Insulin-like growth factor promotes engraftment, differentiation, and functional
      improvement after transfer of embryonic stem cells for myocardial restoration.
AB  - Insulin-like growth factor-1 (IGF-1) promotes myocyte proliferation and can
      reverse cardiac abnormalities when it is administered in the early fetal stage.
      Supplementation of a mouse embryonic stem cell (ESC) suspension with IGF-1 might
      enhance cellular engraftment and host organ-specific differentiation after
      injection in the area of acute myocardial injury. In the study reported here, we
      sought to enhance the restorative effect of ESCs in the injured heart by adding
      IGF-1 to the injected cell population. Green fluorescent protein (GFP)-labeled
      sv129 ESCs (2.5 x 10(5)) were injected into the ischemic area after left anterior
      descending (LAD) artery ligation in BalbC mice. Recombinant mouse IGF-1 (25 ng)
      was added to the cell suspension prior to the injection (n = 5). Echocardiography
      was performed before organ harvest 2 weeks later. The degree of restoration
      (ratio of GFP+ to infarct area), expression of cardiac markers by GFP+ cells,
      inflammatory response, and tumorigenicity were evaluated. Mice with LAD ligation
      only (n = 5) and ESC transfer without IGF-1 (n = 5) served as controls. ESCs
      formed viable grafts and improved cardiac function. Left ventricular wall
      thickness was higher in the IGF-1 group (p = .025). There was a trend toward
      higher fractional shortening in the IGF-treated group. Histological analysis
      demonstrated that IGF-1 promoted expression of alpha-sarcomeric actin (p = .015)
      and major histocompatibility complex class I (p = .01). IGF did not affect the
      cellular response to the donor cells or tumorigenicity. IGF-1 promotes expression
      of cardiomyocyte phenotype in ESCs in vivo. It should be considered as an
      adjuvant to cell transfer for myocardial restoration.

PMID- 15579643
TI  - Transplantation of human embryonic stem cell-derived neural progenitors improves
      behavioral deficit in Parkinsonian rats.
AB  - Human embryonic stem cells (hESCs) may potentially serve as a renewable source of
      cells for transplantation. In Parkinson's disease, hESC-derived dopaminergic (DA)
      neurons may replace the degenerated neurons in the brain. Here, we generated
      highly enriched cultures of neural progenitors from hESCs and grafted the
      progenitors into the striatum of Parkinsonian rats. The grafts survived for at
      least 12 weeks, the transplanted cells stopped proliferating, and teratomas were
      not observed. The grafted cells differentiated in vivo into DA neurons, though at
      a low prevalence similar to that observed following spontaneous differentiation
      in vitro. Transplanted rats exhibited a significant partial correction of D
      amphetamine and apomorphine-induced rotational behavior, along with a significant
      improvement in stepping and placing non-pharmacological behavioral tests. While
      transplantation of uncommitted hESC-derived neural progenitors induced partial
      behavioral recovery, our data indicate that the host-lesioned striatum could not
      direct the transplanted neural progenitors to acquire a dopaminergic fate. Hence,
      induction of their differentiation toward a midbrain fate prior to
      transplantation is probably required for complete correction of behavioral
      deficit. Our observations encourage further developments for the potential use of
      hESCs in the treatment of Parkinson's disease.

PMID- 15579644
TI  - Simultaneous injection of bone marrow cells and stromal cells into bone marrow
      accelerates hematopoiesis in vivo.
AB  - We have previously demonstrated that stromal cells can support the proliferation
      and differentiation of hematopoietic cells in vitro and in vivo and that a major
      histocompatibility complex restriction exists between hematopoietic stem cells
      and stromal cells. We have also found that intra-bone marrow (IBM) injection of
      allogeneic bone marrow cells (BMCs) leads to more rapid reconstitution of
      hematopoietic cells than intravenous injection. In the present study, we examine
      the effect of simultaneous injection of stromal cells and BMCs into the same bone
      marrow on the recovery of donor hematopoietic cells and demonstrate that
      simultaneous IBM injection of BMCs plus stromal cells is more effective in
      reconstituting recipients with donor hematopoietic cells than intravenous
      injection of BMCs plus stromal cells or IBM injection of BMCs alone.

PMID- 15579645
TI  - Comparison of gene expression of umbilical cord vein and bone marrow-derived
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) give origin to the marrow stromal environment that
      supports hematopoiesis. These cells present a wide range of differentiation
      potentials and a complex relationship with hematopoietic stem cells (HSCs) and
      endothelial cells. In addition to bone marrow (BM), MSCs can be obtained from
      other sites in the adult or the fetus. We isolate MSCs from the umbilical cord
      (UC) veins that are morphologically and immunophenotpically similar to MSCs
      obtained from the BM. In culture, these cells are capable of differentiating in
      vitro into adipocytes, osteoblasts, and condrocytes. The gene expression profiles
      of BM-MSCs and of UC-MSCs were compared by serial analysis of gene expression,
      then validated by reverse transcription polymerase chain reaction of selected
      genes. The two lineages shared almost all of the first thousand most expressed
      transcripts, including vimentin, galectin 1, osteonectin, collagens, transgelins,
      annexin A2, and MMP2. Nevertheless, a set of genes related to antimicrobial
      activity and to osteogenesis was more expressed in BM-MSCs, whereas higher
      expression in UC-MSCs was observed for genes that participate in pathways related
      to matrix remodeling via metalloproteinases and angiogenesis. Finally, cultured
      endothelial cells, CD34+ HSCs, MSCs, blood leukocytes, and bulk BM clustered
      together, separated from seven other normal nonhematopoietic tissues, on the
      basis of shared expressed genes. MSCs isolated from UC veins are functionally
      similar to BM-MSCs, but differentially expressed genes may reflect differences
      related to their sites of origin: BM-MSCs would be more committed to
      osteogenesis, whereas UC-MSCs would be more committed to angiogenesis.

PMID- 15579646
TI  - Engineering ex vivo-expanded marrow stromal cells to secrete calcitonin gene
      related peptide using adenoviral vector.
AB  - Calcitonin gene-related peptide (CGRP) is a target for cardiovascular gene
      therapy. Marrow stromal cells (MSCs) hold promise for use in adult stem cell
      based cell and gene therapy. To determine the feasibility of adenoviral-mediated
      CGRP gene transfer into ex vivo-expanded MSCs, rat MSCs were isolated, ex vivo
      expanded, and transduced with adenoviruses. Adprepro-CGRP and AdntlacZ,
      adenoviral vectors containing prepro-CGRP or nuclear-targeted beta-galactosidase
      reporter gene ntlacZ under the control of Rous sarcoma virus promoter, were used.
      In this study, it can be shown that transduction efficiency of adenoviral
      mediated gene transfer into ex vivo-expanded MSCs is dose dependent, transgene
      expression persists for more than 21 days in culture, and adenoviral transduction
      does not alter the proliferation or viability of MSCs. Transduced MSCs retain
      multipotentiality and transgene expression after cell differentiation. The
      expression and secretion of CGRP by Adprepro- CGRP-transduced MSCs was confirmed
      by Western blot analysis and enzyme immunoassay. The secretion of CGRP by
      Adprepro-CGRP-transduced MSCs is dose dependent, and the transduced cells release
      as much as 9.5 +/- 0.4 pmol CGRP/1 x 10(6) cells/48 hours (mean +/- standard
      error of mean, n = 3) into culture medium at a multiplicity of infection of 300.
      Furthermore, culture supernatant from Adprepro-CGRP-transduced MSCs increases
      intracellular cyclic AMP levels in pulmonary artery smooth muscle cells in
      culture. These findings suggest that replication-deficient recombinant adenovirus
      can be used to gene engineer ex vivo-expanded MSCs and that high-level secretion
      of biologically active CGRP can be achieved, underscoring the clinical potential
      of using this novel adult stem cell-based cell and gene therapy strategy for the
      treatment of cardiovascular diseases.

PMID- 15579647
TI  - Determinants of skeletal muscle contributions from circulating cells, bone marrow
      cells, and hematopoietic stem cells.
AB  - To investigate the factors that regulate incorporation into uninjured or damaged
      skeletal muscle of donor markers derived from unfractionated bone marrow (BM)
      cells or from highly purified c-kit+ Thy1.1lo Lin- Sca-1+ hematopoietic stem
      cells (HSCs), we evaluated myofiber chimerism of multiple muscle groups in
      irradiated and transplanted recipient mice and in unirradiated parabiotic
      animals. Uninjured panniculus carnosus, diaphragm, and abdominal muscles
      infrequently incorporated donor markers into myofibers in a subset of animals
      after either BM or HSC transplantation; however, acute muscle injury was
      essential to elicit contributions to triceps surae (TS) and tibialis anterior
      muscles. The low level of incorporation of donor marker-expressing myofibers
      could not be enhanced either by transplantation into newborn recipients or by
      induced migration of HSCs into the periphery. Analysis of muscle chimerism in
      unirradiated animals joined surgically by parabiosis revealed that contributions
      of circulating cells to myofibers in the TS were injury dependent and that at
      least some circulating cells with the potential to contribute to regenerating
      muscle derive from BM, suggesting that hematoablative preconditioning is not
      required for such contributions. In all cases tested, donor-derived myofibers
      expressed both donor-specific and host-specific markers, suggesting that they
      arise by low-level fusion into skeletal muscle of cells that can include the
      progeny of HSCs. It is not yet clear whether such events represent a normal
      myogenic pathway or a pathological response to muscle damage.

PMID- 15579648
TI  - Cellular and molecular regulation of skeletal muscle side population cells.
AB  - Muscle progenitor cells (satellite cells) function in the maintenance and repair
      of adult skeletal muscle. Side population (SP) cells are enriched in repopulating
      activity and also reside in adult skeletal muscle. In this study, we observed
      that Abcg2 is a determinant of the SP cell phenotype. Using reverse transcription
      polymerase chain reaction and immunohistochemical techniques, we localized Abcg2
      expressing cells in the interstitium and in close approximation to the
      vasculature of adult skeletal muscle. Muscle SP cells are able to differentiate
      into myotubes and increase in number after cardiotoxin-induced muscle injury.
      Similar to myogenic progenitor cells, muscle SP cells express Foxk1 and are
      decreased in number in Foxk1 mutant skeletal muscle. Using emerging technologies,
      we examine the molecular signature of muscle SP cells from normal, injured, and
      Foxk1 mutant skeletal muscle to define common and distinct molecular programs. We
      propose that muscle SP cells are progenitor cells that participate in repair and
      regeneration of adult skeletal muscle.

PMID- 15579649
TI  - Lineage differentiation-associated loss of adenoviral susceptibility and
      Coxsackie-adenovirus receptor expression in human mesenchymal stem cells.
AB  - Previous reports debated the effects of differentiation on adenoviral vector
      (AdV) transduction efficiency and Coxsackie-adenovirus receptor (CAR) expression.
      This prompted us to investigate the efficiency of AdV transduction and CAR
      expression in human mesenchymal stem cells (hMSCs) and their differentiated
      progeny. Current results revealed high efficiency (>90%) of AdV transduction and
      a consistent level of CAR expression in hMSCs by the use of AdV carrying the
      enhanced green fluorescent protein reporter gene. Competition of CAR with
      blocking monoclonal antibody RmcB resulted in a reduction in transduction
      efficiency, indicating the CAR involvement in transduction of hMSCs. The cells
      were then induced to differentiate into bone, fat, or neural cells, and results
      demonstrated that the differentiation was accompanied with a consistent decline
      in AdV transduction and a decrement in CAR expression. Cells were infected with
      AdV and then induced into differentiation, and results demonstrated that
      transduced cells preserved differentiation potentials and still had transgene
      expression in a subpopulation of cells for 4 weeks and even in tested lineage
      specific differentiation. According to the present investigation,
      undifferentiated hMSCs can serve as a gene-delivering system, and gene transfer
      into hMSCs before differentiation can resolve the difficulties in transduction of
      their differentiated progeny.

PMID- 15579650
TI  - Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord.
AB  - The Wharton's jelly of the umbilical cord contains mucoid connective tissue and
      fibroblast-like cells. Using flow cytometric analysis, we found that mesenchymal
      cells isolated from the umbilical cord express matrix receptors (CD44, CD105) and
      integrin markers (CD29, CD51) but not hematopoietic lineage markers (CD34, CD45).
      Interestingly, these cells also express significant amounts of mesenchymal stem
      cell markers (SH2, SH3). We therefore investigated the potential of these cells
      to differentiate into cardiomyocytes by treating them with 5-azacytidine or by
      culturing them in cardiomyocyte-conditioned medium and found that both sets of
      conditions resulted in the expression of cardiomyocyte markers, namely N-cadherin
      and cardiac troponin I. We also showed that these cells have multilineage
      potential and that, under suitable culture conditions, are able to differentiate
      into cells of the adipogenic and osteogenic lineages. These findings may have a
      significant impact on studies of early human cardiac differentiation, functional
      genomics, pharmacological testing, cell therapy, and tissue engineering by
      helping to eliminate worrying ethical and technical issues.

PMID- 15579651
TI  - Isolation of mesenchymal stem cells of fetal or maternal origin from human
      placenta.
AB  - Recently we reported that second-trimester amniotic fluid (AF) is an abundant
      source of fetal mesenchymal stem cells (MSCs). In this study, we analyze the
      origin of these MSCs and the presence of MSCs in human-term AF. In addition,
      different parts of the human placenta were studied for the presence of either
      fetal or maternal MSCs. We compared the phenotype and growth characteristics of
      MSCs derived from AF and placenta. Cells from human second-trimester (mean
      gestational age, 19(+2) [standard deviation, +/- 1(+3)] weeks, n = 10) and term
      third-trimester (mean gestational age, 38(+4) [standard deviation, +/- 1] weeks,
      n = 10) AF, amnion, decidua basalis, and decidua parietalis were cultured in M199
      medium supplemented with 10% fetal calf serum and endothelial cell growth factor.
      Cultured cells were immunophenotypically characterized, the adipogenic and
      osteogenic differentiation capacity was tested, and the growth kinetics were
      analyzed. The origin of fetal and maternal cells was determined by molecular
      human leukocyte antigen typing. We successfully isolated MSCs from second
      trimester AF, amnion, and decidua basalis as well as term amnion, decidua
      parietalis, and decidua basalis. In contrast, MSCs were cultured from only 2 out
      of 10 term AF samples. The phenotype of MSCs cultured from different fetal and
      maternal parts of the placenta was comparable. Maternal MSCs from second
      trimester and term decidua basalis and parietalis showed a significantly higher
      expansion capacity than that of MSCs from adult bone marrow (p < .05). Our
      results indicate that both fetal and maternal MSCs can be isolated from the human
      placenta. Amnion is a novel source of fetal MSCs, likely contributing to the
      presence of MSCs in AF. Decidua basalis and decidua parietalis are sources for
      maternal MSCs. The expansion potency from both fetal and maternal placenta
      derived MSCs was higher compared with adult bone marrow-derived MSCs.

PMID- 15579652
TI  - Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia.
AB  - Human mesenchymal stem cells (hMSCs) have the capacity to differentiate along
      several pathways to form bone, cartilage, tendon, muscle, and adipose tissues.
      The adult hMSCs reside in vivo in the bone marrow in niches where oxygen
      concentration is far below the ambient air, which is the most commonly
      encountered laboratory condition. The study reported here was designed to
      determine whether oxygen has a role in the differentiation of hMSCs into
      adipocytes. Indeed, when exposed to atmosphere containing only 1% of oxygen, the
      formation of adipocyte-like phenotype with cytoplasmic lipid inclusions was
      observed. The effect of hypoxia on the expression of adipocyte-specific genes was
      determined by real-time reverse transcription polymerase chain reaction.
      Interestingly, neither of the two central regulators of adipogenesis--the
      transcription factors peroxisome proliferator-activated receptor gamma2 (PPAR
      gamma2) and ADD1/SREBP1c-was induced. Furthermore, hypoxia did not have any
      effect on the transcription of early (lipoprotein lipase) or late (aP2) marker
      genes. By the same token, neither of the mature adipocyte-specific genes--leptin
      and adipophilin--was found responsive to the treatment. High level of induction,
      however, was observed with the PPAR-gamma-induced angiopoietin-related gene,
      PGAR. The lack of an adipocyte-specific transcription pattern thus indicates that
      despite accumulation of the lipid, true adipogenic differentiation did not take
      place. In conclusion, hypoxia appears to exert a potent lipogenic effect
      independent of PPAR-gamma2 maturation pathway.

PMID- 15579654
TI  - Cultured nestin-positive cells from postnatal mouse small bowel differentiate ex
      vivo into neurons, glia, and smooth muscle.
AB  - Little is known about postnatal enteric nervous system (ENS) development, but
      some reports suggest that the postnatal bowel may contain neural stem cells.
      Therefore, we created an in vitro model of desegregation using an enzymatic and
      mechanical tissue technique. This approach yielded a group of cells from the
      small intestine of lactating and adult mice, which ex vivo attach to the culture
      dish; actively proliferate; and express nestin, vimentin, and the pro-neural
      transcription factors neurogenin-2 (ngn-2), Sox-10, and Mash-1. In the conditions
      grown, double immunostains suggest that they differentiate into various cell
      types, particularly neurons, smooth muscle, and glia including 04 protein
      positive cells. They also express the neurotrophic-protein tyrosine kinase (Trk)
      receptors TrkA, TrkB, and TrkC; the low-affinity neurotrophin receptor p75NTR;
      and the glial-derived neurotrophic factor receptors (GFR)alpha-1, GFRalpha-2, and
      GFRalpha-3. The neurons expressed several sensory and motor neurotransmitters
      present in the central and enteric nervous systems, including calcitonin gene
      related peptide, neuropeptideY, peptideYY, substance P, vasoactive intestinal
      polypeptide, and galanin; along with glia, these neurons formed elaborate
      intercellular connections. They also express c-KIT, CD34, CD20, and CD45RO,
      suggesting they either have a hematogenous origin or may differentiate toward
      hematogenous lines. These findings suggest that these cells may be enteric neural
      stem cells (ENSCs); may normally be present in the small intestine; and may have
      the capacity to proliferate and differentiate into neurons, glia, and smooth
      muscle. Further identification and purification of intestinal ENSCs will provide
      a means to study the regulation of their differentiation and should give insight
      into the mechanisms involved in development and remodeling of the ENS. The
      possible therapeutic application of postnatal stem cells such as ENSCs needs to
      be evaluated, including their use for transplantation in the central nervous
      system.

PMID- 15579653
TI  - Expression of telomerase extends the lifespan and enhances osteogenic
      differentiation of adipose tissue-derived stromal cells.
AB  - Expression of TERT, the catalytic protein subunit of the telomerase complex, can
      be used to generate cell lines that expand indefinitely and retain multilineage
      potential. We have created immortal adipose stromal cell lines (ATSCs) by stably
      transducing nonhuman primate-derived ATSCs with a retroviral vector expressing
      TERT. Transduced cells (ATSC-TERT) had an increased level of telomerase activity
      and increased mean telomere length in the absence of malignant cellular
      transformation. Long-term culture of the ATSC-TERT cells demonstrated that the
      cells retain the ability to undergo differentiation along multiple lineages such
      as adipogenic, chondrogenic, and neurogenic. Untransduced cells demonstrated
      markedly reduced multilineage and self-renewal potentials after 12 passages in
      vitro. To determine the functional role of telomerase during osteogenesis, we
      examined osteogenic differentiation potential of ATSC-TERT cells in vitro.
      Compared with naive ATSCs, which typically begin to accumulate calcium after 3-4
      weeks of induction by osteogenic differentiation medium, ATSC-TERT cells were
      found to accumulate significant amounts of calcium after only 1 week of culture
      in osteogenic induction medium. The cells have increased production of
      osteoblastic markers, such as AP2, osteoblast-specific factor 2, chondroitin
      sulfate proteoglycan 4, and the tumor necrosis factor receptor superfamily,
      compared with control ATSCs, indicating that telomerase expression may aid in
      maintaining the osteogenic stem cell pool during in vitro expansion. These
      results show that ectopic expression of the telomerase gene in nonhuman primate
      ATSCs prevents senescence-associated impairment of osteoblast functions and that
      telomerase therapy may be a useful strategy for bone regeneration and repair.

PMID- 15579655
TI  - Mutational analysis of the human SLC26A8 gene: exclusion as a candidate for male
      infertility due to primary spermatogenic failure.
AB  - SLC26A8 is an anion transporter that is solely expressed in the testes. It
      interacts with MgcRacGAP that shows strong structural similarity with the
      Drosophila protein RotundRacGAP, which is established to have an essential role
      for male fertility in the fruit fly. To explore whether the SLC26A8 gene has a
      role in human male infertility, we performed mutational analysis in the coding
      region of the SLC26A8 gene in 83 male infertility patients and two groups of
      controls using single-strand conformational polymorphism and direct sequencing
      methods. We found six novel coding sequence variations, of which five lead to
      amino acid substitutions. All variants were found with similar frequencies in
      both patients and controls, thus suggesting that none of them may be causally
      associated with infertility. We conclude that the SLC26A8 mutations are not a
      common cause of male infertility.

PMID- 15579656
TI  - Fate of SRY, PABY, DYS1, DYZ3 and DYZ1 loci in Indian patients harbouring sex
      chromosomal anomalies.
AB  - We analysed chromosomes, conducted hormonal assays and screened genomic DNA of 34
      patients with or without detectable Y chromosome for the presence/absence of SRY,
      PABY, DYS1, DYZ3 and DYZ1 loci and for mutations in the SRY gene. The samples
      studied represented cases of oligozoospermia, cryptorchidism, Swyer syndrome,
      Turner syndrome, male pseudohermaphroditism, XXY female syndrome, Klinefelter's
      syndrome, repeated abortion and instances of male infertility. Chromosomal
      constitutions and the level of hormones (FSH, LH, PRL, E2 and TSH) were found to
      be abnormal in several cases. A phenotypic female (P20) positive for all the Y
      linked loci screened, showed mutations upstream of the HMG box in the SRY gene.
      In addition, one or more of the Y-linked loci were detected in several phenotypic
      females. Fluorescence in-situ hybridization of metaphase chromosomes and
      interphase nuclei of an aborted fetus with DYZ1 probe detected signals from
      normal to low levels to its complete absence confirming a complex Y chromosome
      mosaicism. Upon DNA analysis, the fetus was found to be positive for all the
      above-mentioned Y-linked loci. Organizational variation within the DYZ1 arrays
      and its correlation with recurrent spontaneous abortion may be followed-up in
      subsequent studies to substantiate this observation. This would augment genetic
      counselling to the affected couples. Prospects of this approach in the overall
      management of clinical cases with sex chromosome-related anomalies are discussed.

PMID- 15579657
TI  - Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of
      hypospadias.
AB  - Hypospadias is one of the most common congenital anomalies. Increased exposure to
      environmental factors (endocrine-disrupting chemicals and smoking) or maternal
      endogenous estrogen may cause hypospadias because male sexual differentiation is
      dependent on normal androgen homeostasis. Moreover, interactions between genetic
      factors and cigarette smoking and other chemicals have been suggested. It has
      been demonstrated that the CYP1A1 metabolizes not only environmental chemicals
      but also estrogens, and glutathione-S-transferases (GSTs) are detoxification
      enzymes that protect cells from toxicants by conjugation with glutathione. In
      this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1
      polymorphisms with hypospadias, a case-control study of 31 case mothers who had
      boys with hypospadias and 64 control mothers was performed in Japan. These
      polymorphisms were investigated by PCR-based methods using DNA from peripheral
      lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and
      homozygous CYP1A1 were less frequent in the case mothers than in the control
      mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74,
      OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal
      smoking on the hypospadias risks among the gene polymorphisms. The results
      suggest that mothers with the CYP1A1 MspI variant allele may have a decreased
      risk for hypospadias.

PMID- 15579658
TI  - Endometriotic cells are resistant to interferon-gamma-induced cell growth
      inhibition and apoptosis: a possible mechanism involved in the pathogenesis of
      endometriosis.
AB  - In order to evaluate the involvement of cell proliferation and apoptosis in the
      pathogenesis of endometriosis, we investigated the effects of interferon-gamma
      (IFN-gamma) on cell growth inhibition and apoptosis of cultured ovarian
      endometriotic cyst stromal cells (ECSC), eutopic endometrial stromal cells with
      endometriosis (ESCwE) and normal endometrial stromal cells (NESC) by modified
      methylthiazoletetrazolium assay, 5-bromo-2'-deoxyuridine incorporation assay and
      internucleosomal DNA fragmentation assay. The expression of apoptosis-related
      molecules and IFN-gamma receptor 1 was also examined in ECSC, ESCwE and NESC
      using western blot analysis. IFN-gamma significantly inhibited cell proliferation
      and DNA synthesis of ESCwE and NESC, and induced apoptosis of these cells. In
      contrast, IFN-gamma did not show apparent effects on the viable cell number, DNA
      synthesis, or apoptosis of ECSC. An up-regulated expression of Bcl-2 and Bcl-X(L)
      proteins was observed in ECSC in comparison with ESCwE and NESC, whereas the
      levels of Bax, Bad, Fas and Fas ligand proteins in ECSC were similar to those in
      ESCwE and NESC. IFN-gamma receptor 1 expression was detected in ECSC, ESCwE and
      NESC. Enhanced expression of anti-apoptotic molecules in the ectopic endometrial
      cells may contribute to the development of endometriosis by conferring resistance
      to cytokine-induced apoptosis and increasing the chance that these cells will
      survive and implant outside the uterus. Further investigations on the regulation
      of cell proliferation in both the endometriotic and the normal endometrium may be
      important for the elucidation of the pathogenesis of endometriosis.

PMID- 15579659
TI  - Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching
      the tissue immune privilege hypothesis from cellular to vesicular level.
AB  - The local immune privilege of the fetus is created by the placenta. Fas ligand
      (FasL) expression in trophoblast has been implied as one of the mechanisms of
      fetal tolerance. However, the expression of membranal FasL by trophoblast has
      failed to explain this role of FasL. Two objections can be raised: (1) there have
      been contradictions considering which trophoblast cells, syncytiotrophoblast (ST)
      or cytotrophoblast, express FasL; (2) in vivo and in vitro studies have shown
      that the membranal form of FasL evokes inflammatory response and thus may promote
      fetal rejection. Using different assays and the FasL-specific antibody G247-4 we
      demonstrate beyond doubt that in vivo, (1) FasL is produced by and stored in the
      first trimester human ST only and (2) the human ST lacks surface membranal FasL.
      Instead, FasL, loaded in microvesicles, is stored in cytoplasmic granules. These
      results complement the recent in vitro studies of the microvesicular form of FasL
      secretion by cultured trophoblast cells, and suggest that placental FasL is
      synthesized by villous ST, stored in microvesicular form and secreted as
      exosomes. Secretion of the exosome-associated form of FasL may be one mechanism
      by which the placenta promotes a state of immune privilege. Additionally, FasL
      expression in Hofbauer cells is also demonstrated.

PMID- 15579660
TI  - Vitamin E supplements: good in theory, but is the theory good?

PMID- 15579661
TI  - The Arabidopsis ATR1 Myb transcription factor controls indolic glucosinolate
      homeostasis.
AB  - Plants derive a number of important secondary metabolites from the amino acid
      tryptophan (Trp), including the growth regulator indole-3-acetic acid (IAA) and
      defense compounds against pathogens and herbivores. In previous work, we found
      that a dominant overexpression allele of the Arabidopsis (Arabidopsis thaliana)
      Myb transcription factor ATR1, atr1D, activates expression of a Trp synthesis
      gene as well as the Trp-metabolizing genes CYP79B2, CYP79B3, and CYP83B1, which
      encode enzymes implicated in production of IAA and indolic glucosinolate (IG)
      antiherbivore compounds. Here, we show that ATR1 overexpression confers elevated
      levels of IAA and IGs. In addition, we show that an atr1 loss-of-function
      mutation impairs expression of IG synthesis genes and confers reduced IG levels.
      Furthermore, the atr1-defective mutation suppresses Trp gene dysregulation in a
      cyp83B1 mutant background. Together, this work implicates ATR1 as a key
      homeostatic regulator of Trp metabolism and suggests that ATR1 can be manipulated
      to coordinately control the suite of enzymes that synthesize IGs.

PMID- 15579662
TI  - Identification of the Arabidopsis palmitoyl-monogalactosyldiacylglycerol delta7
      desaturase gene FAD5, and effects of plastidial retargeting of Arabidopsis
      desaturases on the fad5 mutant phenotype.
AB  - Hexadeca 7,10,13-trienoic acid (16:3Delta(7,10,13)) is one of the most abundant
      fatty acids in Arabidopsis (Arabidopsis thaliana) and a functional component of
      thylakoid membranes, where it is found as an sn-2 ester of
      monogalactosyldiacylglycerol. The Arabidopsis fad5 mutant lacks activity of the
      plastidial palmitoyl-monogalactosyldiacylglycerol Delta7-desaturase FAD5, and is
      characterized biochemically by the absence of 16:3Delta(7,10,13) and
      physiologically by reduced chlorophyll content and a reduced recovery rate after
      photoinhibition. While the fad5 mutation has been mapped, the FAD5 gene was not
      unambiguously identified, and a formal functional characterization by
      complementation of fad5 mutant phenotypes has not been reported. Two candidate
      genes (At3g15850 and At3g15870) predicted to encode plastid-targeted desaturases
      at the fad5 chromosomal locus were cloned from fad5 plants and sequenced. A
      nonsense mutation changing codon TGG (Trp-98) into TGA (stop) was identified in
      At3g15850 (ADS3), whereas the fad5 At3g15870 allele was identical to wild type
      (after correction of a sequencing error in the published wild-type genomic
      At3g15870 sequence). Expression of a genomic clone or cDNA for wild-type
      At3g15850 conferred on fad5 plants the ability to synthesize 16:3Delta(7,10,13)
      and restored leaf chlorophyll content. Arabidopsis carrying a T-DNA insertion in
      At3g15870 had wild-type levels of both 16:3Delta(7,10,13) and chlorophyll.
      Together, these data formally prove that At3g15850 is FAD5. Interestingly, the
      fad5 phenotype was partially complemented when extraplastidial Delta9-desaturases
      of the Arabidopsis desaturase (ADS) family were expressed as fusions with a
      plastidial transit peptide. Tight correlation between leaf 16:3Delta(7,10,13)
      levels and chlorophyll content suggests a role for plastidial fatty acid
      desaturases in thylakoid formation.

PMID- 15579663
TI  - NADP-malate dehydrogenase from unicellular green alga Chlamydomonas reinhardtii.
      A first step toward redox regulation?
AB  - The determinants of the thioredoxin (TRX)-dependent redox regulation of the
      chloroplastic NADP-malate dehydrogenase (NADP-MDH) from the eukaryotic green alga
      Chlamydomonas reinhardtii have been investigated using site-directed mutagenesis.
      The results indicate that a single C-terminal disulfide is responsible for this
      regulation. The redox midpoint potential of this disulfide is less negative than
      that of the higher plant enzyme. The regulation is of an all-or-nothing type,
      lacking the fine-tuning provided by the second N-terminal disulfide found only in
      NADP-MDH from higher plants. The decreased stability of specific cysteine/alanine
      mutants is consistent with the presence of a structural disulfide formed by two
      cysteine residues that are not involved in regulation of activity. Measurements
      of the ability of C. reinhardtii thioredoxin f (TRX f) to activate wild-type and
      site-directed mutants of sorghum (Sorghum vulgare) NADP-MDH suggest that the
      algal TRX f has a redox midpoint potential that is less negative than most those
      of higher plant TRXs f. These results are discussed from an evolutionary point of
      view.

PMID- 15579664
TI  - The role of the cell cycle machinery in resumption of postembryonic development.
AB  - Cell cycle activity is required for plant growth and development, but its
      involvement in the early events that initiate seedling development remains to be
      clarified. We performed experiments aimed at understanding when cell cycle
      progression is activated during seed germination, and what its contribution is
      for proper seedling establishment. To this end, the spatial and temporal
      expression profiles of a large set of cell cycle control genes in germinating
      seeds of Arabidopsis (Arabidopsis thaliana) and white cabbage (Brassica oleracea)
      were analyzed. The in vivo behavior of the microtubular cytoskeleton was
      monitored during Arabidopsis seed germination. Flow cytometry of Arabidopsis
      germinating seeds indicated that DNA replication was mainly initiated at the
      onset of root protrusion, when germination reached its end. Expression analysis
      of cell cycle genes with mRNA in situ localization, beta-glucuronidase assays,
      and semiquantitative reverse transcription-polymerase chain reaction showed that
      transcription of most cell cycle genes was detected only after completion of
      germination. In vivo green fluorescent protein analysis of the microtubule
      cytoskeleton demonstrated that mitosis-specific microtubule arrays occurred only
      when the radicle had started to protrude, although the assembly of the
      microtubular cytoskeleton was promptly activated once germination was initiated.
      Thus, seed germination involves the synthesis and/or activation of a reduced
      number of core cell cycle proteins, which only trigger DNA replication, but is
      not sufficient to drive cells into mitosis. Mitotic divisions are observed only
      after the radicle has protruded and presumably rely on the de novo production of
      other cell cycle regulators.

PMID- 15579665
TI  - Molecular bases for sensitivity to acetyl-coenzyme A carboxylase inhibitors in
      black-grass.
AB  - In grasses, residues homologous to residues Ile-1,781 and Ile-2,041 in the
      carboxyl-transferase (CT) domain of the chloroplastic acetyl-coenzyme A (CoA)
      carboxylase (ACCase) from the grass weed black-grass (Alopecurus myosuroides
      [Huds.]) are critical determinants for sensitivity to two classes of ACCase
      inhibitors, aryloxyphenoxypropionates (APPs) and cyclohexanediones. Using natural
      mutants of black-grass, we demonstrated through a molecular, biological, and
      biochemical approach that residues Trp-2,027, Asp-2,078, and Gly-2,096 are also
      involved in sensitivity to ACCase inhibitors. In addition, residues Trp-2,027 and
      Asp-2,078 are very likely involved in CT activity. Using three-dimensional
      modeling, we found that the side chains of the five residues are adjacent,
      located at the surface of the inside of the cavity of the CT active site, in the
      vicinity of the binding site for APPs. Residues 1,781 and 2,078 are involved in
      sensitivity to both APPs and cyclohexanediones, whereas residues 2,027, 2,041,
      and 2,096 are involved in sensitivity to APPs only. This suggests that the
      binding sites for these two classes of compounds are overlapping, although
      distinct. Comparison of three-dimensional models for black-grass wild-type and
      mutant CTs and for CTs from organisms with contrasted sensitivity to ACCase
      inhibitors suggested that inhibitors fitting into the cavity of the CT active
      site of the chloroplastic ACCase from grasses to reach their active sites may be
      tight. The three-dimensional shape of this cavity is thus likely of high
      importance for the efficacy of ACCase inhibitors.

PMID- 15579666
TI  - Characterization and expression analysis of a serine acetyltransferase gene
      family involved in a key step of the sulfur assimilation pathway in Arabidopsis.
AB  - Ser acetyltransferase (SATase; EC 2.3.1.30) catalyzes the formation of O-acetyl
      Ser from L-Ser and acetyl-CoA, leading to synthesis of Cys. According to its
      position at the decisive junction of the pathways of sulfur assimilation and
      amino acid metabolism, SATases are subject to regulatory mechanisms to control
      the flux of Cys synthesis. In Arabidopsis (Arabidopsis thaliana) there are five
      genes encoding SATase-like proteins. Two isoforms, Serat3;1 and Serat3;2, were
      characterized with respect to their enzymatic properties, feedback inhibition by
      L-Cys, and subcellular localization. Functional identity of Serat3;1 and Serat3;2
      was established by complementation of a SATase-deficient mutant of Escherichia
      coli. Cytosolic localization of Serat3;1 and Serat3;2 was confirmed by using
      fusion construct with the green fluorescent protein. Recombinant Serat3;1 was not
      inhibited by L-Cys, while Serat3;2 was a strongly feedback-inhibited isoform.
      Quantification of expression patterns indicated that Serat2;1 is the dominant
      form expressed in most tissues examined, followed by Serat1;1 and Serat2;2.
      Although Serat3;1 and Serat3;2 were expressed weakly in most tissues, Serat3;2
      expression was significantly induced under sulfur deficiency and cadmium stress
      as well as during generative developmental stages, implying that Serat3;1 and
      Serat3;2 have specific roles when plants are subjected to distinct conditions.
      Transgenic Arabidopsis plants expressing the green fluorescent protein under the
      control of the five promoters indicated that, in all Serat genes, the expression
      was predominantly localized in the vascular system, notably in the phloem. These
      results demonstrate that Arabidopsis employs a complex array of compartment
      specific SATase isoforms with distinct enzymatic properties and expression
      patterns to ensure the provision of Cys in response to developmental and
      environmental changes.

PMID- 15579667
TI  - Breastfeeding rates in the United States by characteristics of the child, mother,
      or family: the 2002 National Immunization Survey.
AB  - OBJECTIVE: In the third quarter of 2001, the National Immunization Survey (NIS)
      began collecting data on the initiation and duration of breastfeeding and whether
      it was the exclusive method of infant feeding. Using the data from the 2002 NIS,
      this study estimates breastfeeding rates in the United States by characteristics
      of the child, mother, or family. METHODS: The NIS uses random-digit dialing to
      survey households nationwide with children 19 to 35 months old about vaccinations
      and then validates the information through a mail survey of the health care
      providers who gave the vaccinations. In 2002, approximately 3500 households from
      the NIS were randomized to 1 of the 3 rotating topical modules that covered
      breastfeeding. RESULTS: More than two thirds (71.4%) of the children had ever
      been breastfed. At 3 months, 42.5% of infants were exclusively breastfed, and
      51.5% were breastfed to some extent. At 6 months, these rates dropped to 13.3%
      and 35.1%, respectively. At 1 year, 16.1% of infants were receiving some breast
      milk. Non-Hispanic black children had the lowest breastfeeding rates.
      Breastfeeding rates also varied by participation in day care or the Women,
      Infants, and Children program, socioeconomic status, and geographic area of
      residence. CONCLUSIONS: Although the rate of breastfeeding initiation in the
      United States is near the national goal of 75%, at 6 and 12 months postpartum the
      rates of breastfeeding duration are still considerably below the national goals
      of 50% and 25%, respectively. In addition, rates of exclusive breastfeeding are
      low. Strenuous public health efforts are needed to improve breastfeeding
      behaviors, particularly among non-Hispanic black women and socioeconomically
      disadvantaged groups.

PMID- 15579668
TI  - Myelomeningocele, temperament patterns, and parental perceptions.
AB  - OBJECTIVE: Description of temperament profiles of children has largely been
      reported in typically developing populations. Children undergo individualized
      assessments of achievement (developmental/academic) and receive individualized
      interventions. In contrast, their individual behavioral styles are not evaluated
      as completely, if at all. For children with developmental disabilities,
      description of temperament characteristics can provide better understanding of
      the already complex child. This study describes temperament characteristics in a
      group of children with myelomeningocele and shunted hydrocephalus (MM/SH).
      METHODS: A consecutive cohort study with historical control group measuring
      temperament characteristics was conducted at a tertiary-level, university
      affiliated, interdisciplinary spina bifida program. Analysis includes group
      comparisons. Primary caregivers of 46 children (age range: 5-12 years) with MM/SH
      completed age-appropriate Carey Temperament Scales questionnaires as a component
      of a larger developmental study. The Carey Temperament Scales comprise a series
      of behavioral rating instruments that assess 9 temperament characteristics:
      activity, adaptability, approach-withdrawal, mood, intensity,
      attention/persistence, distractibility, sensory threshold, and
      rhythmicity/predictability. The Carey questionnaires used in this study were (1)
      the Behavioral Style Questionnaire for children aged 5 to 7 years and (2) the
      Middle Childhood Temperament Questionnaire for those aged 8 to 12 years. Both
      questionnaires assess the same temperament characteristics; the contexts within
      which items were rated were designed to better reflect developmental levels.
      Children were excluded when there were comorbid diagnoses of attention
      deficit/hyperactivity disorder or mental retardation. RESULTS: One-sample normal
      tests (Bonferroni corrected) revealed that children within the MM/SH group
      differed significantly from the standardized population in 5 dimensions: (1)
      adaptability (less adaptable), (2) approach/withdrawal (poor first
      approach/greater withdrawal), (3) distractibility (more distractible), (4)
      attention/persistence (less attentive/persistent), and (5) predictability/rhythm
      (less predictable). Caregiver perceptions of having a difficult-to-manage child
      were significantly correlated with negative mood, more intensity of response, and
      less adaptability. CONCLUSIONS: Temperament profiles previously described in
      typically developing populations (eg, "easy" or "difficult child") were not
      prominent profiles in this group of children with MM/SH. A constellation of
      temperament characteristics not commonly recognized may place these children at
      risk for being contributors to and recipients of misunderstandings of social cues
      and have implications for successful learning within academic, home/community,
      and medical settings.

PMID- 15579669
TI  - Relevance of the Agency for Healthcare Research and Quality Patient Safety
      Indicators for children's hospitals.
AB  - OBJECTIVES: Patient safety indicators (PSIs) were developed by the Agency for
      Healthcare Research and Quality. Our objectives were (1) to apply these
      algorithms to the National Association of Children's Hospitals and Related
      Institutions (NACHRI) Aggregate Case Mix Comparative Database for 1999-2002, (2)
      to establish mean rates for each of the PSI events in children's hospitals, (3)
      to investigate the inadequacies of PSIs in relation to pediatric diagnoses, and
      (4) to express the data in such a way that children's hospitals could use the
      PSIs determined to be appropriate for pediatric use for comparison with their own
      data. In addition, we wanted to use the data to set priorities for ongoing
      clinical investigations and to propose interventions if the indicators
      demonstrated preventable errors. METHODS: The Agency for Healthcare Research and
      Quality PSI algorithms (version 2.1, revision 1) were applied to children's
      hospital administrative data (1.92 million discharges) from the NACHRI Aggregate
      Case Mix Comparative Database for 1999-2002. Rates were measured for the
      following events: complications of anesthesia, death in low-mortality diagnosis
      related groups (DRGs), decubitus ulcer, failure to rescue (ie, death resulting
      from a complication, rather than the primary diagnosis), foreign body left in
      during a procedure, iatrogenic pneumothorax, infection attributable to medical
      care (ie, infections related to surgery or device placement), postoperative
      hemorrhage or hematoma, postoperative pulmonary embolism or venous thrombosis,
      postoperative wound dehiscence, and accidental puncture/laceration. RESULTS:
      Across the 4 years of data, the mean risk-adjusted rates of PSI events ranged
      from 0.01% (0.1 event per 1000 discharges) for a foreign body left in during a
      procedure to 14.0% (140 events per 1000 discharges) for failure to rescue. Review
      of International Classification of Diseases, Ninth Revision, Clinical
      Modification codes associated with each PSI category showed that the failure to
      rescue and death in low-mortality DRG indicators involved very complex cases and
      did not predict preventable events in the majority of cases. The PSI for
      infection attributable to medical care appeared to be accurate the majority of
      the time. Incident risk-adjusted rates of infections attributable to medical care
      averaged 0.35% (3.5 events per 1000 discharges) and varied up to fivefold from
      the lowest rate to the highest rate. The highest rates were up to 1.8 times the
      average. CONCLUSIONS: PSIs derived from administrative data are indicators of
      patient safety concerns and can be relevant as screening tools for children's
      hospitals; however, cases identified by these indicators do not always represent
      preventable events. Some, such as a foreign body left in during a procedure,
      iatrogenic pneumothorax, infection attributable to medical care, decubitus ulcer,
      and venous thrombosis, seem to be appropriate for pediatric care and may be
      directly amenable to system changes. Evidence-based practices regarding those
      particular indicators that have been reported in the adult literature need to be
      investigated in the pediatric population. In their present form, 2 of the
      indicators, namely, failure to rescue and death in low-mortality DRGs, are
      inaccurate for the pediatric population, do not represent preventable errors in
      the majority of pediatric cases, and should not be used to estimate quality of
      care or preventable deaths in children's hospitals. The PSIs can assist
      institutions in prioritizing chart review-based investigations; if clusters of
      validated events emerge in reviews, then improvement activities can be initiated.
      Large aggregate databases, such as the NACHRI Case Mix Database, can help
      establish mean rates of potential pediatric events, giving children's hospitals a
      context within which to examine their own data.

PMID- 15579670
TI  - Microarray analysis of in vitro pericyte differentiation reveals an angiogenic
      program of gene expression.
AB  - The vasculature consists of endothelial cells (ECs) lined by pericyte/vascular
      smooth muscle cells (vSMCs). Pericyte/vSMCs provide support to the mature
      vasculature but are also essential for normal blood vessel development. To
      determine how pericyte-EC communication influences vascular development, we used
      the well-established in vitro model of TGFbeta-stimulated differentiation of
      10T1/2 cells into pericyte/vSMCs. Microarray analysis was performed to identify
      genes that were differentially expressed by induced vs. uninduced 10T1/2 cells.
      We discovered that these cells show an angiogenic program of gene expression,
      with up-regulation of several genes previously implicated in angiogenesis,
      including VEGF, IL-6, VEGF-C, HB-EGF, CTGF, tenascin C, integrin alpha5, and Eph
      receptor A2. Up-regulation of some genes was validated by Western blots and
      immunocytochemistry. We also examined the functional significance of these gene
      expression changes. VEGF and IL-6 alone and in combination were important in
      10T1/2 cell differentiation. Furthermore, we used a coculture system of 10T1/2
      and human umbilical vein ECs (HUVECs), resulting in the formation of cordlike
      structures by the HUVECs. This cordlike structure formation was disrupted when
      neutralizing antibodies to VEGF or IL-6 were added to the coculture system. The
      results of these studies show that factors produced by pericytes may be
      responsible for recruiting ECs and promoting angiogenesis. Therefore, a further
      understanding of the genes involved in pericyte differentiation could provide a
      novel approach for developing anti-angiogenic therapies.

PMID- 15579671
TI  - Anecdotal, historical and critical commentaries on genetics. Gisela Mosig.

PMID- 15579672
TI  - Anecdotal, historical and critical commentaries on genetics. John Maynard Smith:
      January 6, 1920-April 19, 2004.

PMID- 15579673
TI  - Instructors' practices in and attitudes toward teaching ethics in the genetics
      classroom.
AB  - There is strong consensus among educators that training in the ethical and social
      consequences of science is necessary for the development of students into the
      science professionals and well-rounded citizens needed in the future. However,
      this part of the curriculum is not a major focus of most science departments and
      it is not clear if, or how, students receive this training. To determine the
      current status of bioethics education of undergraduate biology students in the
      United States, we surveyed instructors of introductory genetics. We found that
      there was support for more ethics education both in the general curriculum and in
      the genetics classroom than is currently being given. Most instructors devote <5%
      of class time to ethical and social issues in their genetics courses. The
      majority feels that this is inadequate treatment of these topics and most cited
      lack of time as a major reason they were unable to give more attention to
      bioethics. We believe biology departments should take the responsibility to
      ensure that their students are receiving a balanced education. Undergraduate
      students should be adequately trained in ethics either within their science
      courses or in a specialized course elsewhere in the curriculum.

PMID- 15579674
TI  - Experimental adaptation of Salmonella typhimurium to mice.
AB  - Experimental evolution is a powerful approach to study the dynamics and
      mechanisms of bacterial niche specialization. By serial passage in mice, we
      evolved 18 independent lineages of Salmonella typhimurium LT2 and examined the
      rate and extent of adaptation to a mainly reticuloendothelial host environment.
      Bacterial mutation rates and population sizes were varied by using wild-type and
      DNA repair-defective mutator (mutS) strains with normal and high mutation rates,
      respectively, and by varying the number of bacteria intraperitoneally injected
      into mice. After <200 generations of adaptation all lineages showed an increased
      fitness as measured by a faster growth rate in mice (selection coefficients 0.11
      0.58). Using a generally applicable mathematical model we calculated the adaptive
      mutation rate for the wild-type bacterium to be >10(-6)/cell/generation,
      suggesting that the majority of adaptive mutations are not simple point
      mutations. For the mutator lineages, adaptation to mice was associated with a
      loss of fitness in secondary environments as seen by a reduced metabolic
      capability. During adaptation there was no indication that a high mutation rate
      was counterselected. These data show that S. typhimurium can rapidly and
      extensively increase its fitness in mice but this niche specialization is, at
      least in mutators, associated with a cost.

PMID- 15579675
TI  - Combining mathematical models and statistical methods to understand and predict
      the dynamics of antibiotic-sensitive mutants in a population of resistant
      bacteria during experimental evolution.
AB  - Temporarily discontinuing the use of antibiotics has been proposed as a means to
      eliminate resistant bacteria by allowing sensitive clones to sweep through the
      population. In this study, we monitored a tetracycline-sensitive subpopulation
      that emerged during experimental evolution of E. coli K12 MG1655 carrying the
      multiresistance plasmid pB10 in the absence of antibiotics. The fraction of
      tetracycline-sensitive mutants increased slowly over 500 generations from 0.1 to
      7%, and loss of resistance could be attributed to a recombination event that
      caused deletion of the tet operon. To help understand the population dynamics of
      these mutants, three mathematical models were developed that took into
      consideration recurrent mutations, increased host fitness (selection), or a
      combination of both mechanisms (full model). The data were best explained by the
      full model, which estimated a high mutation frequency (lambda = 3.11 x 10(-5))
      and a significant but small selection coefficient (sigma = 0.007). This study
      emphasized the combined use of experimental data, mathematical models, and
      statistical methods to better understand and predict the dynamics of evolving
      bacterial populations, more specifically the possible consequences of
      discontinuing the use of antibiotics.

PMID- 15579676
TI  - Insertion-sequence-mediated mutations isolated during adaptation to growth and
      starvation in Lactococcus lactis.
AB  - We studied the activity of three multicopy insertion sequence (IS) elements in 12
      populations of Lactococcus lactis IL1403 that evolved in the laboratory for 1000
      generations under various environmental conditions (growth or starvation and
      shaken or stationary). Using RFLP analysis of single-clone representatives of
      each population, nine IS-mediated mutations were detected across all
      environmental conditions and all involving IS981. When it was assumed that these
      mutations were neutral, their frequency was higher under shaken than under
      stationary conditions, possibly due to oxygen stress. We characterized seven of
      the nine mutations at the molecular level and studied their population dynamics
      where possible. Two were simple insertions into new positions and the other five
      were recombinational deletions (of <1->10 kb) among existing and new copies of
      IS981; in all but one case these mutations disrupted gene functions. The best
      candidate beneficial mutations were two deletions of which similar versions were
      detected in two populations each. One of these two parallel deletions, affecting
      a gene involved in bacteriophage resistance, showed intermediate rearrangements
      and may also have resulted from increased local transposition rates.

PMID- 15579677
TI  - Host factors that affect Ty3 retrotransposition in Saccharomyces cerevisiae.
AB  - The retrovirus-like element Ty3 of Saccharomyces cerevisiae integrates at the
      transcription initiation region of RNA polymerase III. To identify host genes
      that affect transposition, a collection of insertion mutants was screened using a
      genetic assay in which insertion of Ty3 activates expression of a tRNA
      suppressor. Fifty-three loci were identified in this screen. Corresponding
      knockout mutants were tested for the ability to mobilize a galactose-inducible
      Ty3, marked with the HIS3 gene. Of 42 mutants tested, 22 had phenotypes similar
      to those displayed in the original assay. The proteins encoded by the defective
      genes are involved in chromatin dynamics, transcription, RNA processing, protein
      modification, cell cycle regulation, nuclear import, and unknown functions. These
      mutants were induced for Ty3 expression and assayed for Gag3p protein, integrase,
      cDNA, and Ty3 integration upstream of chromosomal tDNA(Val(AAC)) genes. Most
      mutants displayed differences from the wild type in one or more intermediates,
      although these were typically not as severe as the genetic defect. Because a
      relatively large number of genes affecting retrotransposition can be identified
      in yeast and because the majority of these genes have mammalian homologs, this
      approach provides an avenue for the identification of potential antiviral
      targets.

PMID- 15579678
TI  - Genotype-environment interactions of spontaneous mutations for vegetative fitness
      in the human pathogenic fungus Cryptococcus neoformans.
AB  - Spontaneous mutation is the ultimate source of all genetic variation. By
      interacting with environmental factors, genetic variation determines the
      phenotype and fitness of individuals in natural populations. However, except in a
      few model organisms, relatively little is known about the patterns of genotype
      environment interactions of spontaneous mutations. Here I examine the rates of
      spontaneous mutation and the patterns of genotype-environment interaction of
      mutations affecting vegetative growth in the human fungal pathogen Cryptococcus
      neoformans. Eight mutation accumulation (MA) lines were established from a single
      clone on the nutrient-rich medium YEPD for each of two temperatures, 25 degrees
      and 37 degrees. Cells from generations 100, 200, 400, and 600 for each of the 16
      MA lines were stored and assayed for vegetative growth rates under each of four
      conditions: (i) 25 degrees on SD (a synthetic dextrose minimal medium); (ii) 25
      degrees on YEPD; (iii) 37 degrees on SD; and (iv) 37 degrees on YEPD. Both MA
      conditions and assay environments for vegetative growth showed significant
      influence on the estimates of genomic mutation rates, average effect per
      mutation, and mutational heritability. Significant genotype-environment
      interactions were detected among the newly accumulated spontaneous mutations.
      Overall, clones from MA lines maintained at 37 degrees showed less decline in
      vegetative fitness than those maintained at 25 degrees. The result suggests that
      a high-temperature environment might be very important for the maintenance of the
      ability to grow at a high temperature. Results from comparisons between clinical
      and environmental samples of C. neoformans were consistent with laboratory
      experimental population analyses. This study calls into question our long
      standing view that warm-blooded mammals were only occasional and accidental hosts
      of this human fungal pathogen.

PMID- 15579679
TI  - Compartmentalization of the yeast meiotic nucleus revealed by analysis of ectopic
      recombination.
AB  - As yeast cells enter meiosis, chromosomes move from a centromere-clustered (Rabl)
      to a telomere-clustered (bouquet) configuration and then to states of progressive
      homolog pairing where telomeres are more dispersed. It is uncertain at which
      stage of this process sequences commit to recombine with each other. Previous
      analyses using recombination between dispersed homologous sequences (ectopic
      recombination) support the view that, on average, homologs are aligned end to end
      by the time of commitment to recombination. We have undertaken further analyses
      incorporating new inserts, chromosome rearrangements, an alternate mode of
      recombination initiation, and mutants that disrupt nuclear structure or telomere
      metabolism. Our findings support previous conclusions and reveal that distance
      from the nearest telomere is an important parameter influencing recombination
      between dispersed sequences. In general, the farther dispersed sequences are from
      their nearest telomere, the less likely they are to engage in ectopic
      recombination. Neither the mode of initiating recombination nor the formation of
      the bouquet appears to affect this relationship. We suggest that aspects of
      telomere localization and behavior influence the organization and mobility of
      chromosomes along their entire length, during a critical period of meiosis I
      prophase that encompasses the homology search.

PMID- 15579680
TI  - The amino terminus of the Saccharomyces cerevisiae DNA helicase Rrm3p modulates
      protein function altering replication and checkpoint activity.
AB  - The Pif1 family of DNA helicases is conserved from yeast to humans. Although the
      helicase domains of family members are well conserved, the amino termini of these
      proteins are not. The Saccharomyces cerevisiae genome encodes two Pif1 family
      members, Rrm3p and Pif1p, that have very different functions. To determine if the
      amino terminus of Rrm3p contributes to its role in promoting fork progression at
      >1000 discrete chromosomal sites, we constructed a deletion series that lacked
      portions of the 249-amino-acid amino terminus. The phenotypes of cells expressing
      alleles that lacked all or most of the amino terminus were indistinguishable from
      those of rrm3Delta cells. Rrm3p deletion derivatives that lacked smaller portions
      of the amino terminus were also defective, but the extent of replication pausing
      at tRNA genes, telomeres, and ribosomal DNA (rDNA) was not as great as in
      rrm3Delta cells. Deleting only 62 amino acids from the middle of the amino
      terminus affected only rDNA replication, suggesting that the amino terminus can
      confer locus-specific effects. Cells expressing a fusion protein consisting of
      the Rrm3p amino terminus and the Pif1p helicase domain displayed defects similar
      to rrm3Delta cells. These data demonstrate that the amino terminus of Rrm3p is
      essential for Rrm3p function. However, the helicase domain of Rrm3p also
      contributes to its functional specificity.

PMID- 15579681
TI  - The budding yeast mei5 and sae3 proteins act together with dmc1 during meiotic
      recombination.
AB  - Here we provide evidence that the Mei5 and Sae3 proteins of budding yeast act
      together with Dmc1, a meiosis-specific, RecA-like recombinase. The mei5 and sae3
      mutations reduce sporulation, spore viability, and crossing over to the same
      extent as dmc1. In all three mutants, these defects are largely suppressed by
      overproduction of Rad51. In addition, mei5 and sae3, like dmc1, suppress the cell
      cycle arrest phenotype of the hop2 mutant. The Mei5, Sae3, and Dmc1 proteins
      colocalize to foci on meiotic chromosomes, and their localization is mutually
      dependent. The localization of Rad51 to chromosomes is not affected in either
      mei5 or sae3. Taken together, these observations suggest that the Mei5 and Sae3
      proteins are accessory factors specific to Dmc1. We speculate that Mei5 and Sae3
      are necessary for efficient formation of Dmc1-containing nucleoprotein filaments
      in vivo.

PMID- 15579682
TI  - Mutation and evolution of microsatellite loci in Neurospora.
AB  - The patterns of mutation and evolution at 13 microsatellite loci were studied in
      the filamentous fungal genus Neurospora. First, a detailed investigation was
      performed on five microsatellite loci by sequencing each microsatellite, together
      with its nonrepetitive flanking regions, from a set of 147 individuals from eight
      species of Neurospora. To elucidate the genealogical relationships among
      microsatellite alleles, repeat number was mapped onto trees constructed from
      flanking-sequence data. This approach allowed the potentially convergent
      microsatellite mutations to be placed in the evolutionary context of the less
      rapidly evolving flanking regions, revealing the complexities of the mutational
      processes that have generated the allelic diversity conventionally assessed in
      population genetic studies. In addition to changes in repeat number, frequent
      substitution mutations within the microsatellites were detected, as were
      substitutions and insertion/deletions within the flanking regions. By comparing
      microsatellite and flanking-sequence divergence, clear evidence of interspecific
      allele length homoplasy and microsatellite mutational saturation was observed,
      suggesting that these loci are not appropriate for inferring phylogenetic
      relationships among species. In contrast, little evidence of intraspecific
      mutational saturation was observed, confirming the utility of these loci for
      population-level analyses. Frequency distributions of alleles within species were
      generally consistent with the stepwise mutational model. By comparing variation
      within species at the microsatellites and the flanking-sequence, estimated
      microsatellite mutation rates were approximately 2500 times greater than mutation
      rates of flanking DNA and were consistent with estimates from yeast and fruit
      flies. A positive relationship between repeat number and variance in repeat
      number was significant across three genealogical depths, suggesting that longer
      microsatellite alleles are more mutable than shorter alleles. To test if the
      observed patterns of microsatellite variation and mutation could be generalized,
      an additional eight microsatellite loci were characterized and sequenced from a
      subset of the same Neurospora individuals.

PMID- 15579683
TI  - White mutants of Chlamydomonas reinhardtii are defective in phytoene synthase.
AB  - Carotenoids play an integral and essential role in photosynthesis and
      photoprotection in plants and algae. A collection of Chlamydomonas reinhardtii
      mutants lacking carotenoids was characterized for pigment and tocopherol (vitamin
      E) composition, growth phenotypes under different light conditions, and the
      molecular basis of their mutant phenotype. The carotenoid-less mutants, or
      "white" mutants, were also deficient in chlorophylls but had approximately twice
      the tocopherol content of the wild type. White mutants grew in the dark but were
      unable to survive in the light, even under very low light conditions on acetate
      containing medium. Genetic crosses and recombination tests revealed that all
      individual white mutants in the collection are alleles of a single gene, lts1,
      and the white phenotype was closely linked to a marker located in the phytoene
      synthase gene. DNA sequencing of the phytoene synthase gene from each of the
      mutants revealed nonsense, missense, frameshift, and splice site mutations.
      Transformation with a wild-type copy of the phytoene synthase gene was able to
      complement the lts1-210 mutation. Together, these results show that all the white
      mutants examined in this work are affected in the phytoene synthase gene.

PMID- 15579684
TI  - Gene interactions in Caenorhabditis elegans define DPY-31 as a candidate
      procollagen C-proteinase and SQT-3/ROL-4 as its predicted major target.
AB  - Zinc metalloproteases of the BMP-1/TOLLOID family (also known as astacins) are
      extracellular enzymes involved in important developmental processes in metazoans.
      We report the characterization of the Caenorhabditis elegans gene dpy-31, which
      encodes the first essential astacin metalloprotease identified in this organism.
      Loss-of-function mutations in dpy-31 result in cuticle defects, abnormal
      morphology, and embryonic lethality, indicating that dpy-31 is required for
      formation of the collagenous exoskeleton. DPY-31 is widely expressed in the
      hypodermal cells, which are responsible for cuticle secretion. We have
      investigated the dpy-31 function through reversion analysis. While complete
      reversion can be obtained only by intragenic suppressors, reversion of the Dpy-31
      lethal phenotype also can be caused by dominant extragenic suppressors. Nine
      extragenic suppressors carry mutations in the uniquely essential collagen gene
      sqt-3, which we show is the same gene as rol-4. Most mutations exhibit the
      unusual property of exclusively dominant suppression and all affect the sequence
      of the SQT-3 collagen C terminus. This suggests that DPY-31 is responsible for C
      terminal proteolytic processing of collagen trimers and is therefore a structural
      and functional homolog of vertebrate BMP-1. The results also demonstrate the
      critical importance of the collagen C-terminal sequence, which is highly
      conserved among all 49 members of the SQT-3 subfamily.

PMID- 15579685
TI  - Chromosome-wide regulation of meiotic crossover formation in Caenorhabditis
      elegans requires properly assembled chromosome axes.
AB  - Most sexually reproducing organisms depend on the regulated formation of
      crossovers, and the consequent chiasmata, to accomplish successful segregation of
      homologous chromosomes at the meiosis I division. A robust, chromosome-wide
      crossover control system limits chromosome pairs to one crossover in most meioses
      in the nematode Caenorhabditis elegans; this system has been proposed to rely on
      structural integrity of meiotic chromosome axes. Here, we test this hypothesis
      using a mutant, him-3(me80), that assembles reduced levels of meiosis-specific
      axis component HIM-3 along cohesin-containing chromosome axes. Whereas pairing,
      synapsis, and crossing over are eliminated when HIM-3 is absent, the him-3(me80)
      mutant supports assembly of synaptonemal complex protein SYP-1 along some paired
      chromosomes, resulting in partial competence for chiasma formation. We present
      both genetic and cytological evidence indicating that the him-3(me80) mutation
      leads to an increased incidence of meiotic products with two crossovers. These
      results indicate that limiting the amount of a major axis component results in a
      reduced capacity to communicate the presence of a (nascent) crossover and/or to
      discourage others in response.

PMID- 15579686
TI  - The identities of sym-2, sym-3 and sym-4, three genes that are synthetically
      lethal with mec-8 in Caenorhabditis elegans.
AB  - On the basis of synthetic lethality, five genes in Caenorhabditis elegans are
      known to be redundant with the mec-8 gene, which encodes a protein that contains
      two copies of an RNA recognition motif (RRM) and affects alternative RNA
      splicing. The molecular identities of two of the redundant genes, sym-1 and sym
      5, were previously reported. The remaining three genes have now been cloned, and
      their synthetically lethal phenotypes with mec-8 are described in more detail.
      Animals homozygous for mec-8 and sym-2 loss-of-function mutations die during late
      embryogenesis. The SYM-2 predicted protein contains three RRMs; we propose that
      SYM-2 and MEC-8 can substitute for each other in promoting the maturation of the
      transcripts of a vital gene. Animals homozygous for mutations in mec-8 and in
      either sym-3 or sym-4 have the same striking defect: they arrest development just
      prior to or just after hatching with a pharynx that appears fully formed but is
      not properly attached to the body cuticle. sym-3 encodes a protein of unknown
      function with orthologs in Drosophila and mammals. sym-4 encodes a WD-repeat
      protein and may also have orthologs in Drosophila and mammals. We propose that
      SYM-3 and SYM-4 contribute to a common developmental pathway that is redundant
      with a MEC-8-dependent pathway.

PMID- 15579687
TI  - Genetic analysis of the Caenorhabditis elegans pax-6 locus: roles of paired
      domain-containing and nonpaired domain-containing isoforms.
AB  - PAX-6 proteins are involved in eye and brain development in many animals. In the
      nematode Caenorhabditis elegans the pax-6 locus encodes multiple PAX-6 isoforms
      both with and without a paired domain. Mutations in the C. elegans pax-6 locus
      can be grouped into three classes. Mutations that affect paired domain-containing
      isoforms cause defects in epidermal morphogenesis, epidermal cell fates, and
      gonad cell migration and define the class I (vab-3) complementation group. The
      class II mutation mab-18(bx23) affects nonpaired domain-containing isoforms and
      transforms the fate of a sensory organ in the male tail. Class III mutations
      affect both paired domain and nonpaired domain isoforms; the most severe class
      III mutations are candidate null mutations in pax-6. Class III mutant phenotypes
      do not resemble a simple sum of class I and class II phenotypes. A comparison of
      class I and class III phenotypes indicates that PAX-6 isoforms can interact
      additively, synergistically, or antagonistically, depending on the cellular
      context.

PMID- 15579688
TI  - Evolution of P elements in natural populations of Drosophila willistoni and D.
      sturtevanti.
AB  - To determine how population structure of the host species affects the spread of
      transposable elements and to assess the strength of selection acting on different
      structural regions, we sequenced P elements from strains of Drosophila willistoni
      and Drosophila sturtevanti sampled from across the distributions of these
      species. Elements from D. sturtevanti exhibited considerable sequence variation,
      and similarity among them was correlated to geographic distance between
      collection sites. By contrast, all D. willistoni elements sampled were
      essentially identical (pi < 0.2%) and exhibited patterns typical of a recent
      population expansion. While the canonical P elements sampled from D. sturtevanti
      appear to be long-time residents in that species, a rapid expansion of a very
      young canonical P-element lineage is suggested in D. willistoni, overcoming
      barriers such as large geographical distances and moderate levels of population
      subdivision. Between-species comparisons reveal selective constraints on P
      element evolution, as indicated by significantly different substitution rates in
      noncoding, silent, and replacement sites. Most remarkably, in addition to
      replacement sites, selection pressure appears to be strong in the first and third
      introns and in the 3' and 5' flanking regions.

PMID- 15579689
TI  - Drosophila crinkled, mutations of which disrupt morphogenesis and cause
      lethality, encodes fly myosin VIIA.
AB  - Myosin VIIs provide motor function for a wide range of eukaryotic processes. We
      demonstrate that mutations in crinkled (ck) disrupt the Drosophila myosin VIIA
      heavy chain. The ck/myoVIIA protein is present at a low level throughout fly
      development and at the same level in heads, thoraxes, and abdomens. Severe ck
      alleles, likely to be molecular nulls, die as embryos or larvae, but all allelic
      combinations tested thus far yield a small fraction of adult "escapers" that are
      weak and infertile. Scanning electron microscopy shows that escapers have defects
      in bristles and hairs, indicating that this motor protein plays a role in the
      structure of the actin cytoskeleton. We generate a homology model for the
      structure of the ck/myosin VIIA head that indicates myosin VIIAs, like myosin
      IIs, have a spectrin-like, SH3 subdomain fronting their N terminus. In addition,
      we establish that the two myosin VIIA FERM repeats share high sequence similarity
      with only the first two subdomains of the three-lobed structure that is typical
      of canonical FERM domains. Nevertheless, the approximately 100 and approximately
      75 amino acids that follow the first two lobes of the first and second FERM
      domains are highly conserved among myosin VIIs, suggesting that they compose a
      conserved myosin tail homology 7 (MyTH7) domain that may be an integral part of
      the FERM domain or may function independently of it. Together, our data suggest a
      key role for ck/myoVIIA in the formation of cellular projections and other actin
      based functions required for viability.

PMID- 15579690
TI  - A deficiency screen for dominant suppressors of telomeric silencing in
      Drosophila.
AB  - Heterochromatin is a specialized chromatin structure in chromosomal regions
      associated with repeated DNA sequences and low concentrations of genes. Formation
      of heterochromatin is determined in large part by enzymes that modify histones
      and structural proteins that bind to these modified histones in a cooperative
      fashion. In Drosophila, mutations in genes that encode heterochromatic proteins
      are often dominant and increase expression of genes placed into heterochromatic
      positions. To find components of telomeric heterochromatin in Drosophila, we
      screened a collection of autosomal deficiencies for dominant suppressors of
      silencing of a transgene at the telomere of chromosome 2L. While many deficiency
      chromosomes are associated with dominant suppressors, in the cases tested on
      chromosome 2 the suppressor mapped to the 2L telomere, rather than the
      deficiency. We infer that background effects may hamper the search for genes that
      play a role in telomeric heterochromatin formation and that either very few genes
      participate in this pathway or mutations in these genes are not dominant
      suppressors of telomeric position effect. The data also suggest that the 2L
      telomere region plays a major role in telomeric silencing.

PMID- 15579691
TI  - The enhancer-blocking activity of the Fab-7 boundary from the Drosophila bithorax
      complex requires GAGA-factor-binding sites.
AB  - In the work reported here we have analyzed the role of the GAGA factor [encoded
      by the Trithorax-like (Trl) gene] in the enhancer-blocking activity of
      Frontabdominal-7 (Fab-7), a domain boundary element from the Drosophila
      melanogaster bithorax complex (BX-C). One of the three nuclease hypersensitive
      sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences
      for the GAGA factor, a protein known to be involved in the formation and/or
      maintenance of nucleosome-free regions of chromatin. GAGA protein has been shown
      to localize to the Fab-7 boundary in vivo, and we show that it recognizes
      sequences from HS1 in vitro. Using two different transgene assays we demonstrate
      that GAGA-factor-binding sites are necessary but not sufficient for full Fab-7
      enhancer-blocking activity. We show that distinct GAGA sites are required for
      different enhancer-blocking activities at different stages of development. We
      also show that the enhancer-blocking activity of the endogenous Fab-7 boundary is
      sensitive to mutations in the gene encoding the GAGA factor Trithorax-like.

PMID- 15579692
TI  - Drosophila klarsicht has distinct subcellular localization domains for nuclear
      envelope and microtubule localization in the eye.
AB  - The Drosophila klarsicht (klar) gene is required for developmentally regulated
      migrations of photoreceptor cell nuclei in the eye. klar encodes a large (
      approximately 250 kD) protein with only one recognizable amino acid sequence
      motif, a KASH (Klar, Anc-1, Syne-1 homology) domain, at its C terminus. It has
      been proposed that Klar facilitates nuclear migration by linking the nucleus to
      the microtubule organizing center (MTOC). Here we perform genetic and
      immunohistochemical experiments that provide a critical test of this model. We
      analyze mutants in the endogenous klar gene and also flies that express deleted
      forms of Klar protein from transgenes. We find that the KASH domain of Klar is
      critical for perinuclear localization and for function. In addition, we find that
      the N-terminal portion of Klar is also important for function and contains a
      domain that localizes the protein to microtubules apical to the nucleus. These
      results provide strong support for a model in which Klar links the nucleus to the
      MTOC.

PMID- 15579693
TI  - Mutations in Su(var)205 and Su(var)3-7 suppress P-element-dependent silencing in
      Drosophila melanogaster.
AB  - In Drosophila melanogaster, the w(+) transgene in P[lacW]ci(Dplac) is uniformly
      expressed throughout the adult eye. However, when other P elements are present,
      this w(+) transgene is randomly silenced and this produces a variegated eye
      phenotype. This P-element-dependent silencing (PDS) is limited to w(+) transgenes
      inserted in a specific region on chromosome 4. In a screen for genetic modifiers
      of PDS, we isolated mutations in Su(var)205, Su(var)3-7, and two unidentified
      genes that suppress this variegated phenotype. Therefore, only a few of the genes
      encoding heterochromatic modifiers act dose dependently in PDS. In addition, we
      recovered two spontaneous mutations of P[lacW]ci(Dplac) that variegate in the
      absence of P elements. These P[lacW]i(Dplac) derivatives have a gypsy element
      inserted proximally to the P[lacW]ci(Dplac) insert. The same mutations that
      suppress PDS also suppress w(+) silencing from these P[lacW]ci(Dplac) derivative
      alleles. This indicates that both cis-acting changes in sequence and trans-acting
      P elements cause a similar change in chromatin structure that silences w(+)
      expression in P[lacW]ci(Dplac). Together, these results confirm that PDS occurs
      at P[lacW]ci(Dplac) because of the chromatin structure at this chromosomal
      position. Studying w(+) variegation from P[lacW]ci(Dplac) provides a model for
      the interactions that can enhance heterochromatic silencing at single P-element
      inserts.

PMID- 15579694
TI  - Additivity and trans-acting effects on gene expression in male Drosophila
      simulans.
AB  - Understanding how genetic variation is maintained begins with a comprehensive
      description of what types of genetic variation exist, the extent and magnitude of
      the variation, and patterns discernable in that variation. However, such studies
      have focused primarily on DNA sequence data and have ignored genetic variation at
      other hierarchical levels of genetic information. Microarray technology permits
      an examination of genetic variation at the level of mRNA abundance. Utilizing a
      round-robin design, we present a quantitative description of variation in mRNA
      abundance in terms of GCA (general combining ability or additive variance). We
      test whether genes significant for GCA are randomly distributed across
      chromosomes and use a nonparametric approach to demonstrate that the magnitude of
      the variation is not random for GCA. We find that there is a paucity of genes
      significant for GCA on the X relative to the autosomes. The overall magnitude of
      the effects for GCA on the X tends to be lower than that on the autosomes and is
      contributed by rare alleles of larger effect. Due to male hemizygosity, GCA for X
      linked phenotypes must be due to trans-acting factors, while GCA for autosomal
      phenotypes may be due to cis- or trans-acting factors. The contrast in the amount
      of variation between the X and the autosomes suggests that both cis and trans
      factors contribute to variation for expression in D. simulans with the
      preponderance of effects being trans. This nonrandom patterning of genetic
      variation in gene expression data with respect to chromosomal context may be due
      to hemizygosity in the male.

PMID- 15579695
TI  - Rapid evolution through gene duplication and subfunctionalization of the testes
      specific alpha4 proteasome subunits in Drosophila.
AB  - Gene duplication is an important mechanism for acquiring new genes and creating
      genetic novelty in organisms. Evidence suggests that duplicated genes are
      retained at a much higher rate than originally thought and that functional
      divergence of gene copies is a major factor promoting their retention in the
      genome. We find that two Drosophila testes-specific alpha4 proteasome subunit
      genes (alpha4-t1 and alpha4-t2) have a higher polymorphism within species and are
      significantly more diverged between species than the somatic alpha4 gene. Our
      data suggest that following gene duplication, the alpha4-t1 gene experienced
      relaxed selective constraints, whereas the alpha4-t2 gene experienced positive
      selection acting on several codons. We report significant heterogeneity in
      evolutionary rates among all three paralogs at homologous codons, indicating that
      functional divergence has coincided with genic divergence. Reproductive
      subfunctionalization may allow for a more rapid evolution of reproductive traits
      and a greater specialization of testes function. Our data add to the increasing
      evidence that duplicated genes experience lower selective constraints and in some
      cases positive selection following duplication. Newly duplicated genes that are
      freer from selective constraints may provide a mechanism for developing new
      interactions and a pathway for the evolution of new genes.

PMID- 15579696
TI  - Genetic interactions of Drosophila melanogaster arrest reveal roles for
      translational repressor Bruno in accumulation of Gurken and activity of Delta.
AB  - arrest mutants have pleiotropic phenotypes, ranging from an early arrest of
      oogenesis to irregular embryonic segmentation defects. One function of arrest is
      in translational repression of oskar mRNA; this biochemical activity is presumed
      to be involved in other functions of arrest. To identify genes that could provide
      insight into how arrest contributes to translational repression or that may be
      targets for arrest-dependent translational control, we screened deficiency
      mutants for dominant modification of the arrest phenotype. Only four of the many
      deficiencies tested, which cover approximately 30% of the genome, modified the
      starting phenotype. One enhancer, identified fortuitously, is the Star gene. Star
      interaction with arrest results in excess Gurken protein, supporting the model
      that gurken is a target of repression. Two modifiers were mapped to individual
      genes. One is Lk6, which encodes a protein kinase predicted to regulate the rate
      limiting initiation factor eIF4E. The second is Delta. The interaction between
      arrest and Delta mimics the phenotype of homozygous Delta mutants, suggesting
      that arrest could positively control Delta activity. Indeed, arrest mutants have
      significantly reduced levels of Delta protein at the interface of germline and
      follicle cells.

PMID- 15579697
TI  - Evolutionarily stable infection by a male-killing endosymbiont in Drosophila
      innubila: molecular evidence from the host and parasite genomes.
AB  - Maternally inherited microbes that spread via male-killing are common pathogens
      of insects, yet very little is known about the evolutionary duration of these
      associations. The few examples to date indicate very recent, and thus potentially
      transient, infections. A male-killing strain of Wolbachia has recently been
      discovered in natural populations of Drosophila innubila. The population-level
      effects of this infection are significant: approximately 35% of females are
      infected, infected females produce very strongly female-biased sex ratios, and
      the resulting population-level sex ratio is significantly female biased. Using
      data on infection prevalence and Wolbachia transmission rates, infected
      cytoplasmic lineages are estimated to experience a approximately 5% selective
      advantage relative to uninfected lineages. The evolutionary history of this
      infection was explored by surveying patterns of polymorphism in both the host and
      parasite genomes, comparing the Wolbachia wsp gene and the host mtDNA COI gene to
      five host nuclear genes. Molecular data suggest that this male-killing infection
      is evolutionarily old, a conclusion supported with a simple model of parasite and
      mtDNA transmission dynamics. Despite a large effective population size of the
      host species and strong selection to evolve resistance, the D. innubila-Wolbachia
      association is likely at a stable equilibrium that is maintained by imperfect
      maternal transmission of the bacteria rather than partial resistance in the host
      species.

PMID- 15579698
TI  - Evolutionary expressed sequence tag analysis of Drosophila female reproductive
      tracts identifies genes subjected to positive selection.
AB  - Genes whose products are involved in reproduction include some of the fastest
      evolving genes found within the genomes of several organisms. Drosophila has long
      been used to study the function and evolutionary dynamics of genes thought to be
      involved in sperm competition and sexual conflict, two processes that have been
      hypothesized to drive the adaptive evolution of reproductive molecules. Several
      seminal fluid proteins (Acps) made in the Drosophila male reproductive tract show
      evidence of rapid adaptive evolution. To identify candidate genes in the female
      reproductive tract that may be involved in female-male interactions and that may
      thus have been subjected to adaptive evolution, we used an evolutionary
      bioinformatics approach to analyze sequences from a cDNA library that we have
      generated from Drosophila female reproductive tracts. We further demonstrate that
      several of these genes have been subjected to positive selection. Their
      expression in female reproductive tracts, presence of signal
      sequences/transmembrane domains, and rapid adaptive evolution indicate that they
      are prime candidates to encode female reproductive molecules that interact with
      rapidly evolving male Acps.

PMID- 15579699
TI  - Genomic deletions of the Drosophila melanogaster Hsp70 genes.
AB  - Homologous recombination can produce directed mutations in the genomes of a
      number of model organisms, including Drosophila melanogaster. One of the most
      useful applications has been to delete target genes to generate null alleles. In
      Drosophila, specific gene deletions have not yet been produced by this method. To
      test whether such deletions could be produced by homologous recombination in D.
      melanogaster we set out to delete the Hsp70 genes. Six nearly identical copies of
      this gene, encoding the major heat-shock protein in Drosophila, are found at two
      separate but closely linked loci. This arrangement has thwarted standard genetic
      approaches to generate an Hsp70-null fly, making this an ideal test of gene
      targeting. In this study, ends-out targeting was used to generate specific
      deletions of all Hsp70 genes, including one deletion that spanned approximately
      47 kb. The Hsp70-null flies are viable and fertile. The results show that genomic
      deletions of varied sizes can be readily generated by homologous recombination in
      Drosophila.

PMID- 15579700
TI  - Gene deletions by ends-in targeting in Drosophila melanogaster.
AB  - Following the advent of a gene targeting technique in Drosophila, different
      methods have been developed to modify the Drosophila genome. The initial
      demonstration of gene targeting in flies used an ends-in method, which generates
      a duplication of the target locus. The duplicated locus can then be efficiently
      reduced to a single copy by generating a double-strand break between the
      duplicated segments. This method has been used to knock out target genes by
      introducing point mutations. A derivative of this method is reported here. By
      using different homologous regions for the targeting and reduction steps, a
      complete deletion of the target gene can be generated to produce a definitive
      null allele. The breakpoints of the deletion can be precisely controlled. Unlike
      ends-out targeting, this method does not leave exogenous sequence at the deleted
      locus. Three endogenous genes, Sir2, Sirt2, and p53 have been successfully
      deleted using this method.

PMID- 15579701
TI  - Controlling for the effects of history and nonequilibrium conditions in gene flow
      estimates in northern bullfrog (Rana catesbeiana) populations.
AB  - Nonequilibrium conditions due to either allopatry followed by secondary contact
      or recent range expansion can confound measurements of gene flow among
      populations in previously glaciated regions. We determined the scale at which
      gene flow can be estimated among breeding aggregations of bullfrogs (Rana
      catesbeiana) at the northern limit of their range in Ontario, Canada, using seven
      highly polymorphic DNA microsatellite loci. We first identified breeding
      aggregations that likely share a common history, determined from the pattern of
      allelic richness, factorial correspondence analysis, and a previously published
      mtDNA phylogeography, and then tested for regional equilibrium by evaluating the
      association between pairwise F(ST) and geographic distance. Regional breeding
      aggregations in eastern Ontario separated by <100 km were determined to be at or
      near equilibrium. High levels of gene flow were measured using traditional F
      statistics and likelihood estimates of Nm. Similarly high levels of recent
      migration (past one to three generations) were estimated among the breeding
      aggregations using nonequilibrium methods. We also show that, in many cases,
      breeding aggregations separated by up to tens of kilometers are not genetically
      distinct enough to be considered separate genetic populations. These results have
      important implications both for the identification of independent "populations"
      and in assessing the effect of scale in detecting patterns of genetic equilibrium
      and gene flow.

PMID- 15579702
TI  - The Dominant white, Dun and Smoky color variants in chicken are associated with
      insertion/deletion polymorphisms in the PMEL17 gene.
AB  - Dominant white, Dun, and Smoky are alleles at the Dominant white locus, which is
      one of the major loci affecting plumage color in the domestic chicken. Both
      Dominant white and Dun inhibit the expression of black eumelanin. Smoky arose in
      a White Leghorn homozygous for Dominant white and partially restores
      pigmentation. PMEL17 encodes a melanocyte-specific protein and was identified as
      a positional candidate gene due to its role in the development of eumelanosomes.
      Linkage analysis of PMEL17 and Dominant white using a red jungle fowl/White
      Leghorn intercross revealed no recombination between these loci. Sequence
      analysis showed that the Dominant white allele was exclusively associated with a
      9-bp insertion in exon 10, leading to an insertion of three amino acids in the
      PMEL17 transmembrane region. Similarly, a deletion of five amino acids in the
      transmembrane region occurs in the protein encoded by Dun. The Smoky allele
      shared the 9-bp insertion in exon 10 with Dominant white, as expected from its
      origin, but also had a deletion of 12 nucleotides in exon 6, eliminating four
      amino acids from the mature protein. These mutations are, together with the
      recessive silver mutation in the mouse, the only PMEL17 mutations with phenotypic
      effects that have been described so far in any species.

PMID- 15579703
TI  - Conserved function of medaka pink-eyed dilution in melanin synthesis and its
      divergent transcriptional regulation in gonads among vertebrates.
AB  - Medaka is emerging as a model organism for the study of vertebrate development
      and genetics, and its effectiveness in forward genetics should prove equal to
      that of zebrafish. Here, we identify by positional cloning a gene responsible for
      the medaka i-3 albino mutant. i-3 larvae have weakly tyrosinase-positive cells
      but lack strongly positive and dendritic cells, suggesting loss of fully
      differentiated melanophores. The region surrounding the i-3 locus is syntenic to
      human 19p13, but a BAC clone covering the i-3 locus contained orthologs located
      at 15q11-13, including OCA2 (P). Medaka P consists of 842 amino acids and shares
      approximately 65% identity with mammalian P proteins. The i-3 mutation is a four
      base deletion in exon 13, which causes a frameshift and truncation of the
      protein. We detected medaka P transcripts in melanin-producing eyeballs and
      (putative) skin melanophores on embryos and an alternatively spliced form in the
      non-melanin-producing ovary or oocytes. The mouse p is similarly expressed in
      gonads, but not alternatively spliced. This is the first isolation of
      nonmammalian P, the functional mechanism of action of which has not yet been
      elucidated, even in mammals. Further investigation of the functions of P proteins
      and the regulation of their expression will provide new insight into body color
      determination and gene evolution.

PMID- 15579704
TI  - Microarray profiling for differential gene expression in ovaries and ovarian
      follicles of pigs selected for increased ovulation rate.
AB  - A unique index line of pigs created by long-term selection ovulates on average
      6.7 more ova than its randomly selected control line. Expression profiling
      experiments were conducted to identify differentially expressed genes in ovarian
      tissues of the index and control lines during days 2-6 of the follicular phase of
      the estrous cycle. Fluorescently labeled cDNAs derived from ovary and follicle
      RNA were cohybridized on microarray slides (n = 90) containing 4608 follicle
      derived probes printed in duplicate. Statistical analysis of the resulting
      approximately 1.6 million data points with a mixed-model approach identified 88
      and 74 unique probes, representing 71 and 59 unique genes, which are
      differentially expressed between lines in the ovary and ovarian follicles of
      different size classes, respectively. These findings indicate that long-term
      selection for components of litter size has caused significant changes in
      physiological control of the dynamics of follicular maturation. Genes involved
      with steroid synthesis, tissue remodeling, and apoptosis, in addition to several
      genes not previously associated with ovarian physiology or with unknown function,
      were found to be differentially expressed between lines. This study reveals many
      potential avenues of investigation for seeking new insights into ovarian
      physiology and the quantitative genetic control of reproduction.

PMID- 15579705
TI  - Testing predictions of the double-strand break repair model relating to crossing
      over in Mammalian cells.
AB  - In yeast, four-stranded, biparental "joint molecules" containing a pair of
      Holliday junctions are demonstrated intermediates in the repair of meiotic double
      strand breaks (DSBs). Genetic and physical evidence suggests that when joint
      molecules are resolved by the cutting of each of the two Holliday junctions,
      crossover products result at least most of the time. The double-strand break
      repair (DSBR) model is currently accepted as a paradigm for acts of DSB repair
      that lead to crossing over. In this study, a well-defined mammalian gene
      targeting assay was used to test predictions that the DSBR model makes about the
      frequency and position of hDNA in recombinants generated by crossing over. The
      DSBR model predicts that hDNA will frequently form on opposite sides of the DSB
      in the two homologous sequences undergoing recombination [half conversion (HC);
      5:3, 5:3 segregation]. By examining the segregation patterns of poorly repairable
      small palindrome genetic markers, we show that this configuration of hDNA is
      rare. Instead, in a large number of recombinants, full conversion (FC) events in
      the direction of the unbroken chromosomal sequence (6:2 segregation) were
      observed on one side of the DSB. A conspicuous fraction of the unidirectional FC
      events was associated with normal 4:4 marker segregation on the other side of the
      DSB. In addition, a large number of recombinants displayed evidence of hDNA
      formation. In several, hDNA was symmetrical on one side of the DSB, suggesting
      that the two homologous regions undergoing recombination swapped single strands
      of the same polarity. These data are considered within the context of modified
      versions of the DSBR model.

PMID- 15579706
TI  - A complex interaction of imprinted and maternal-effect genes modifies sex
      determination in Odd Sex (Ods) mice.
AB  - The transgenic insertional mouse mutation Odd Sex (Ods) represents a model for
      the long-range regulation of Sox9. The mutation causes complete female-to-male
      sex reversal by inducing a male-specific expression pattern of Sox9 in XX Ods/+
      embryonic gonads. We previously described an A/J strain-specific suppressor of
      Ods termed Odsm1(A). Here we show that phenotypic sex depends on a complex
      interaction between the suppressor and the transgene. Suppression can be achieved
      only if the transgene is transmitted paternally. In addition, the suppressor
      itself exhibits a maternal effect, suggesting that it may act on chromatin in the
      early embryo.

PMID- 15579707
TI  - High-resolution mapping and functional analysis of se2.1: a major stigma
      exsertion quantitative trait locus associated with the evolution from allogamy to
      autogamy in the genus Lycopersicon.
AB  - The degree to which stigmas are exserted above the stamen in flowers is a key
      determinant of cross-pollination (and hence allogamy) in many plant species. Most
      species in the genus Lycopersicon are obligate or facultative outcrossers and
      bear flowers with highly exserted stigmas. In contrast, the cultivated tomato
      (Lycopersicon esculentum) bears flowers with flush or inserted stigmas promoting
      self-fertilization. It has been observed that a major QTL, se2.1, on chromosome 2
      is responsible for a large portion of phenotypic variation for this trait and
      that mutation(s) at this locus were likely involved in the evolution from
      allogamy to autogamy in this genus. To understand the genetic and molecular basis
      of stigma exsertion, we have conducted a high-resolution mapping at the
      chromosome region harboring the se2.1 QTL. The results indicate that this is a
      compound locus, comprising at least five tightly linked genes, one controlling
      style length, three controlling stamen length, and the other affecting anther
      dehiscence, a taxonomic character used to distinguish Lycopersicon species from
      other solanaceous species. This cluster of genes may represent the vestiges of an
      ancient coadapted gene complex in controlling mating behavior.

PMID- 15579708
TI  - Comparing the linkage maps of the close relatives Arabidopsis lyrata and A.
      thaliana.
AB  - We have constructed a genetic map of Arabidopsis lyrata, a self-incompatible
      relative of the plant model species A. thaliana. A. lyrata is a diploid (n = 8)
      species that diverged from A. thaliana (n = 5) approximately 5 MYA. Mapping was
      conducted in a full-sib progeny of two unrelated F(1) hybrids between two
      European populations of A. lyrata ssp. petraea. We used the least-squares method
      of the Joinmap program for map construction. The gross chromosomal differences
      between the two species were most parsimoniously explained with three fusions,
      two reciprocal translocations, and one inversion. The total map length was 515
      cM, and the distances were 12% larger than those between corresponding markers in
      the linkage map of A. thaliana. The 72 markers, consisting of microsatellites and
      gene-based markers, were spaced on average every 8 cM. Transmission ratio
      distortion was extensive, and most distortions were specific to each reciprocal
      cross, suggesting cytoplasmic interactions. We estimate locations and most
      probable genotype frequencies of transmission ratio distorting loci (TRDL) with a
      Bayesian method and discuss the possible reasons for the observed distortions.

PMID- 15579709
TI  - Dissection of floral pollination syndromes in Petunia.
AB  - Animal-mediated pollination is essential in the reproductive biology of many
      flowering plants and tends to be associated with pollination syndromes, sets of
      floral traits that are adapted to particular groups of pollinators. The
      complexity and functional convergence of various traits within pollination
      syndromes are outstanding examples of biological adaptation, raising questions
      about their mechanisms and origins. In the genus Petunia, complex pollination
      syndromes are found for nocturnal hawkmoths (P. axillaris) and diurnal bees (P.
      integrifolia), with characteristic differences in petal color, corolla shape,
      reproductive organ morphology, nectar quantity, nectar quality, and fragrance. We
      dissected the Petunia syndromes into their most important phenotypic and genetic
      components. They appear to include several distinct differences, such as cell
      growth and cell-division patterns in the basal third of the petals, elongation of
      the ventral stamens, nectar secretion and nectar sugar metabolism, and enzymatic
      differentiation in the phenylpropanoid pathway. In backcross-inbred lines of
      species-derived chromosome segments in a transposon tagging strain of P. hybrida,
      one to five quantitative trait loci were identified for each syndrome component.
      Two loci for stamen elongation and nectar volume were confirmed in introgression
      lines and showed large allelic differences. The combined data provide a framework
      for a detailed understanding of floral syndromes from their developmental and
      molecular basis to their impact on animal behavior. With its molecular genetic
      tools, this Petunia system provides a novel venue for a pattern of adaptive
      radiation that is among the most characteristic of flowering plants.

PMID- 15579710
TI  - Fine-scale genetic structure and gene dispersal in Centaurea corymbosa
      (Asteraceae). II. Correlated paternity within and among sibships.
AB  - The fine-scale pattern of correlated paternity was characterized within a
      population of the narrow-endemic model plant species, Centaurea corymbosa, using
      microsatellites and natural progeny arrays. We used classical approaches to
      assess correlated mating within sibships and developed a new method based on
      pairwise kinship coefficients to assess correlated paternity within and among
      sibships in a spatio-temporal perspective. We also performed numerical
      simulations to assess the relative significance of different mechanisms promoting
      correlated paternity and to compare the statistical properties of different
      estimators of correlated paternity. Our new approach proved very informative to
      assess which factors contributed most to correlated paternity and presented good
      statistical properties. Within progeny arrays, we found that about one-fifth of
      offspring pairs were full-sibs. This level of correlated mating did not result
      from correlated pollen dispersal events (i.e., pollen codispersion) but rather
      from limited mate availability, the latter being due to limited pollen dispersal
      distances, the heterogeneity of pollen production among plants, phenological
      heterogeneity and, according to simulations, the self-incompatibility system. We
      point out the close connection between correlated paternity and the "TwoGener"
      approach recently developed to infer pollen dispersal and discuss the conditions
      to be met when applying the latter.

PMID- 15579711
TI  - Genome scanning for interspecific differentiation between two closely related oak
      species [Quercus robur L. and Q. petraea (Matt.) Liebl.].
AB  - Interspecific differentiation values (G(ST)) between two closely related oak
      species (Quercus petraea and Q. robur) were compiled across different studies
      with the aim to explore the distribution of differentiation at the genome level.
      The study was based on a total set of 389 markers (isozymes, AFLPs, SCARs,
      microsatellites, and SNPs) for which allelic frequencies were estimated in pairs
      of populations sampled throughout the sympatric distribution of the two species.
      The overall distribution of G(ST) values followed an L-shaped curve with most
      markers exhibiting low species differentiation (G(ST) < 0.01) and only a few loci
      reaching >10% levels. Twelve percent of the loci exhibited significant G(ST)
      deviations to neutral expectations, suggesting that selection contributed to
      species divergence. Coding regions expressed higher differentiation than
      noncoding regions. Among the 389 markers, 158 could be mapped on the 12 linkage
      groups of the existing Q. robur genetic map. Outlier loci with large G(ST) values
      were distributed over 9 linkage groups. One cluster of three outlier loci was
      found within 0.51 cM; but significant autocorrelation of G(ST) was observed at
      distances <2 cM. The size and distribution of genomic regions involved in species
      divergence are discussed in reference to hitchhiking effects and disruptive
      selection.

PMID- 15579713
TI  - Phylogenetic analysis of 5'-noncoding regions from the ABA-responsive rab16/17
      gene family of sorghum, maize and rice provides insight into the composition,
      organization and function of cis-regulatory modules.
AB  - Phylogenetic analysis of sequences from gene families and homologous genes from
      species of varying divergence can be used to identify conserved noncoding
      regulatory elements. In this study, phylogenetic analysis of 5'-noncoding
      sequences was optimized using rab17, a well-characterized ABA-responsive gene
      from maize, and five additional rab16/17 homologs from sorghum and rice.
      Conserved 5'-noncoding sequences among the maize, sorghum, and rice rab16/17
      homologs were identified with the aid of the software program FootPrinter and by
      screening for known transcription-factor-binding sites. Searches for 7 of 8
      (7/8)bp sequence matches within aligned 5'-noncoding segments of the rab genes
      identified many of the cis-elements previously characterized by biochemical
      analysis in maize rab17 plus several additional putative regulatory elements.
      Differences in the composition of conserved noncoding sequences among rab16/17
      genes were related to variation in rab gene mRNA levels in different tissues and
      to response to ABA treatment using qRT-PCR. Absence of a GRA-like element in the
      promoter of sorghum dhn2 relative to maize rab17 was correlated with an
      approximately 85-fold reduction of dhn2 RNA in sorghum shoots. Overall, we
      conclude that phylogenetic analysis of gene families among rice, sorghum, and
      maize will help identify regulatory sequences in the noncoding regions of genes
      and contribute to our understanding of grass gene regulatory networks.

PMID- 15579714
TI  - Rearrangements in the Cf-9 disease resistance gene cluster of wild tomato have
      resulted in three genes that mediate Avr9 responsiveness.
AB  - Cf resistance genes in tomato confer resistance to the fungal leaf pathogen
      Cladosporium fulvum. Both the well-characterized resistance gene Cf-9 and the
      related 9DC gene confer resistance to strains of C. fulvum that secrete the Avr9
      protein and originate from the wild tomato species Lycopersicon pimpinellifolium.
      We show that 9DC and Cf-9 are allelic, and we have isolated and sequenced the
      complete 9DC cluster of L. pimpinellifolium LA1301. This 9DC cluster harbors five
      full-length Cf homologs, including orthologs of the most distal homologs of the
      Cf-9 cluster and three central 9DC genes. Two 9DC genes (9DC1 and 9DC2) have an
      identical coding sequence, whereas 9DC3 differs at its 3' terminus. From a
      detailed comparison of the 9DC and Cf-9 clusters, we conclude that the Cf-9 and
      Hcr9-9D genes from the Cf-9 cluster are ancestral to the first 9DC gene and that
      the three 9DC genes were generated by subsequent intra- and intergenic unequal
      recombination events. Thus, the 9DC cluster has undergone substantial
      rearrangements in the central region, but not at the ends. Using transient
      transformation assays, we show that all three 9DC genes confer Avr9
      responsiveness, but that 9DC2 is likely the main determinant of Avr9 recognition
      in LA1301.

PMID- 15579712
TI  - Haplotype structure and phenotypic associations in the chromosomal regions
      surrounding two Arabidopsis thaliana flowering time loci.
AB  - The feasibility of using linkage disequilbrium (LD) to fine-map loci underlying
      natural variation in Arabidopsis thaliana was investigated by looking for
      associations between flowering time and marker polymorphism in the genomic
      regions containing two candidate genes, FRI and FLC, both of which are known to
      contribute to natural variation in flowering. A sample of 196 accessions was
      used, and polymorphism was assessed by sequencing a total of 17 roughly 500-bp
      fragments. Using a novel Bayesian algorithm based on haplotype similarity, we
      demonstrate that LD could have been used to fine-map the FRI gene to a roughly 30
      kb region and to identify two common loss-of-function alleles. Interestingly,
      because of genetic heterogeneity, simple single-marker associations would not
      have been able to map FRI with nearly the same precision. No clear evidence for
      previously unknown alleles at either locus was found, but the effect of
      population structure in causing false positives was evident.

PMID- 15579715
TI  - Deletion polymorphism in wheat chromosome regions with contrasting recombination
      rates.
AB  - Polymorphism for deletions was investigated in 1027 lines of tetraploid and
      hexaploid wheat and 420 lines of wheat diploid ancestors. A total of 26 deletions
      originating during the evolution of polyploid wheat were discovered among 155
      investigated loci. Wheat chromosomes were divided into a proximal, low
      recombination interval containing 69 loci and a distal, high-recombination
      interval containing 86 loci. A total of 23 deletions involved loci in the distal,
      high-recombination interval and only 3 involved loci in the proximal, low
      recombination interval. The rates of DNA loss differed by several orders of
      magnitude in the two intervals. The rate of diploidization of polyploid wheat by
      deletions was estimated and was shown to have proceeded faster in the distal,
      high-recombination interval than in the proximal, low-recombination interval.

PMID- 15579716
TI  - An Arabidopsis thaliana plasma membrane proton pump is essential for pollen
      development.
AB  - The plasma membrane proton pump (H(+)-ATPase) found in plants and fungi is a P
      type ATPase with a polypeptide sequence, structure, and in vivo function similar
      to the mammalian sodium pump (Na(+), K(+)-ATPase). Despite its hypothetical
      importance for generating and maintaining the proton motive force that energizes
      the carriers and channels that underlie plant nutrition, genetic evidence for
      such a central function has not yet been reported. Using a reverse genetic
      approach for investigating each of the 11 isoforms in the Arabidopsis H(+)-ATPase
      (AHA) gene family, we found that one member, AHA3, is essential for pollen
      formation. A causative role for AHA3 in male gametogenesis was proven by
      complementation with a normal transgenic gene and rescue of the mutant phenotype
      back to wild type. We also investigated the requirement for phosphorylation of
      the penultimate threonine, which is found in most members of the AHA family and
      is thought to be involved in regulating catalytic activity. We demonstrated that
      a T948D mutant form of the AHA3 gene rescues the mutant phenotype in knockout
      AHA3 plants, but T948A does not, providing the first in planta evidence in
      support of the model in which phosphorylation of this amino acid is essential.

PMID- 15579717
TI  - Mapping quantitative trait loci with censored observations.
AB  - The existing statistical methods for mapping quantitative trait loci (QTL) assume
      that the phenotype follows a normal distribution and is fully observed. These
      assumptions may not be satisfied when the phenotype pertains to the survival time
      or failure time, which has a skewed distribution and is usually subject to
      censoring due to random loss of follow-up or limited duration of the experiment.
      In this article, we propose an interval-mapping approach for censored failure
      time phenotypes. We formulate the effects of QTL on the failure time through
      parametric proportional hazards models and develop efficient likelihood-based
      inference procedures. In addition, we show how to assess genome-wide statistical
      significance. The performance of the proposed methods is evaluated through
      extensive simulation studies. An application to a mouse cross is provided.

PMID- 15579718
TI  - Maximum-likelihood estimation of demographic parameters using the frequency
      spectrum of unlinked single-nucleotide polymorphisms.
AB  - A maximum-likelihood method for demographic inference is applied to data sets
      consisting of the frequency spectrum of unlinked single-nucleotide polymorphisms
      (SNPs). We use simulation analyses to explore the effect of sample size and
      number of polymorphic sites on both the power to reject the null hypothesis of
      constant population size and the properties of two- and three-dimensional maximum
      likelihood estimators (MLEs). Large amounts of data are required to produce
      accurate demographic inferences, particularly for scenarios of recent growth.
      Properties of the MLEs are highly dependent upon the demographic scenario, as
      estimates improve with a more ancient time of growth onset and smaller degree of
      growth. Severe episodes of growth lead to an upward bias in the estimates of the
      current population size, and that bias increases with the magnitude of growth.
      One data set of African origin supports a model of mild, ancient growth, and
      another is compatible with both constant population size and a variety of growth
      scenarios, rejecting greater than fivefold growth beginning >36,000 years ago.
      Analysis of a data set of European origin indicates a bottlenecked population
      history, with an 85% population reduction occurring approximately 30,000 years
      ago.

PMID- 15579719
TI  - Evolution of dominance in metabolic pathways.
AB  - Dominance is a form of phenotypic robustness to mutations. Understanding how such
      robustness can evolve provides a window into how the relation between genotype
      and phenotype can evolve. As such, the issue of dominance evolution is a question
      about the evolution of inheritance systems. Attempts at explaining the evolution
      of dominance have run into two problems. One is that selection for dominance is
      sensitive to the frequency of heterozygotes. Accordingly, dominance cannot evolve
      unless special conditions lead to the presence of a high frequency of mutant
      alleles in the population. Second, on the basis of theoretical results in
      metabolic control analysis, it has been proposed that metabolic systems possess
      inherent constraints. These hypothetical constraints imply the default
      manifestation of dominance of the wild type with respect to the effects of
      mutations at most loci. Hence, some biologists have maintained that an
      evolutionary explanation is not relevant to dominance. In this article, we put
      into question the hypothetical assumption of default metabolic constraints. We
      show that this assumption is based on an exclusion of important nonlinear
      interactions that can occur between enzymes in a pathway. With an a priori
      exclusion of such interactions, the possibility of epistasis and hence dominance
      modification is eliminated. We present a theoretical model that integrates enzyme
      kinetics and population genetics to address dominance evolution in metabolic
      pathways. In the case of mutations that decrease enzyme concentrations, and given
      the mechanistic constraints of Michaelis-Menten-type catalysis, it is shown that
      dominance of the wild type can be extensively modified in a two-enzyme pathway.
      Moreover, we discuss analytical results indicating that the conclusions from the
      two-enzyme case can be generalized to any number of enzymes. Dominance
      modification is achieved chiefly through changes in enzyme concentrations or
      kinetic parameters such as k(cat), both of which can alter saturation levels. Low
      saturation translates into higher levels of dominance with respect to mutations
      that decrease enzyme concentrations. Furthermore, it is shown that in the two
      enzyme example, dominance evolves as a by-product of selection in a manner that
      is insensitive to the frequency of heterozygotes. Using variation in k(cat) as an
      example of modifier mutations, it is shown that the latter can have direct
      fitness effects in addition to dominance modification effects. Dominance
      evolution can occur in a frequency-insensitive manner as a result of selection
      for such dual-effects alleles. This type of selection may prove to be a common
      pattern for the evolution of phenotypic robustness to mutations.

PMID- 15579720
TI  - Quantitative trait loci (QTL) detection in multicross inbred designs: recovering
      QTL identical-by-descent status information from marker data.
AB  - Mapping quantitative trait loci in plants is usually conducted using a population
      derived from a cross between two inbred lines. The power of such QTL detection
      and the parameter estimates depend largely on the choice of the two parental
      lines. Thus, the QTL detected in such populations represent only a small part of
      the genetic architecture of the trait. In addition, the effects of only two
      alleles are characterized, which is of limited interest to the breeder, while
      common pedigree breeding material remains unexploited for QTL mapping. In this
      study, we extend QTL mapping methodology to a generalized framework, based on a
      two-step IBD variance component approach, applicable to any type of breeding
      population obtained from inbred parents. We then investigate with simulated data
      mimicking conventional breeding programs the influence of different estimates of
      the IBD values on the power of QTL detection. The proposed method would provide
      an alternative to the development of specifically designed recombinant
      populations, by utilizing the genetic variation actually managed by plant
      breeders. The use of these detected QTL in assisting breeding would thus be
      facilitated.

PMID- 15579721
TI  - A unified statistical model for functional mapping of environment-dependent
      genetic expression and genotype x environment interactions for ontogenetic
      development.
AB  - The effects of quantitative trait loci (QTL) on phenotypic development may depend
      on the environment (QTL x environment interaction), other QTL (genetic
      epistasis), or both. In this article, we present a new statistical model for
      characterizing specific QTL that display environment-dependent genetic
      expressions and genotype x environment interactions for developmental
      trajectories. Our model was derived within the maximum-likelihood-based mixture
      model framework, incorporated by biologically meaningful growth equations and
      environment-dependent genetic effects of QTL, and implemented with the EM
      algorithm. With this model, we can characterize the dynamic patterns of genetic
      effects of QTL governing growth curves and estimate the global effect of the
      underlying QTL during the course of growth and development. In a real example
      with rice, our model has successfully detected several QTL that produce
      differences in their genetic expression between two contrasting environments.
      These detected QTL cause significant genotype x environment interactions for some
      fundamental aspects of growth trajectories. The model provides the basis for
      deciphering the genetic architecture of trait expression adjusted to different
      biotic and abiotic environments and genetic relationships for growth rates and
      the timing of life-history events for any organism.

PMID- 15579722
TI  - Uncovering novel cell cycle players through the inactivation of securin in
      budding yeast.
AB  - Budding yeast securin/Pds1p, an inhibitor of the anaphase activator
      separase/Esp1p, is involved in several checkpoint pathways and in promoting
      Esp1p's nuclear localization. Using a modified synthetic genetic array (SGA)
      screen for genes that become essential in the absence of Pds1p, we uncovered
      roles for uncharacterized genes in cell cycle processes, including Esp1p
      activation.

PMID- 15579723
TI  - Exacerbations and time spent outdoors in chronic obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease have a progressive reduction
      in activity, although its time scale and the contribution of exacerbations are
      unknown. A rolling cohort of 147 patients (101 male; mean age, 88.5 years; and
      forced expiratory volume in 1 second as percent predicted, 38.4%) were monitored
      for a median of 1,044 days (interquartile range, 685 to 1,779) over an 8-year
      period starting in March 1996. Patients recorded any increase in daily
      respiratory symptoms and time spent outside their home. They completed the St.
      George's Respiratory Questionnaire yearly. They experienced 1,465 exacerbations
      and time outdoors decreased by -0.16 hours/day per year (p < 0.001). This decline
      was faster in frequent exacerbators (p = 0.011). Before exacerbation, the
      patients stayed indoors all day for 2.1 days/week (on any day 34.1% were at
      home), but for 5 weeks postexacerbation they spent 2.5 days/week at home (p <
      0.001) (44.4% remaining at home at onset; p = 0.021). St. George's total,
      activity, and impact scores were independently associated with time outdoors (p <
      0.005), but not with symptom score. In conclusion, time spent outside the home
      declines over time and acutely at exacerbation. Patients with frequent
      exacerbations are more likely to become housebound and need targeting in
      rehabilitation programs.

PMID- 15579724
TI  - Induced sputum 8-isoprostane concentrations in inflammatory airway diseases.
AB  - Induced sputum 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) concentrations may be
      a useful marker of oxidative stress in airways disease. This study examines
      oxidative stress (measured by 8-iso-PGF(2alpha)) in airway disease according to
      disease type (asthma and bronchiectasis), disease activity (stable and acute
      asthma), and disease pattern (intermittent, mild, moderate, and severe persistent
      asthma). We compared subjects with stable asthma (n = 71) and bronchiectasis (n =
      23) with healthy control subjects (n = 29). Another group of patients with asthma
      (n = 39) were assessed during and after acute exacerbation. Induced sputum 8-iso
      PGF(2alpha) concentrations were validated and found to be elevated in subjects
      with stable asthma and bronchiectasis versus control subjects (median
      [interquartile range] 216 [103-389] and 698 [264-1,613] ng/L vs. 123 [41-290]
      ng/L, p < 0.001) and increased as clinical asthma pattern worsened (intermittent
      115 [42-153], mild persistent 116 [89-229] ng/L, moderate persistent 183 [110
      317] ng/L, severe persistent 387 [102-587] ng/L; p = 0.010). Sputum 8-iso
      PGF(2alpha) concentrations were elevated during acute asthma and decreased with
      recovery (458 [227-950] ng/L vs. 214 [148-304] ng/L, p = 0.0002). We conclude
      that 8-iso-PGF(2alpha) is involved in the pathophysiology of inflammatory airway
      diseases, being related to disease type, pattern, and activity. Analysis of 8-iso
      PGF(2alpha) concentrations in induced sputum provides a useful tool for
      monitoring oxidative stress and investigating strategies aimed at reducing
      oxidative stress in airways disease.

PMID- 15579725
TI  - Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and
      exercise in emphysema.
AB  - Endobronchial valve placement improves pulmonary function in some patients with
      chronic obstructive pulmonary disease, but its effects on exercise physiology
      have not been investigated. In 19 patients with a mean (SD) FEV(1) of 28.4
      (11.9)% predicted, studied before and 4 weeks after unilateral valve insertion,
      functional residual capacity decreased from 7.1 (1.5) to 6.6 (1.7) L (p = 0.03)
      and diffusing capacity rose from 3.3 (1.1) to 3.7 (1.2) mmol . minute(-1) . kPa(
      1) (p = 0.03). Cycle endurance time at 80% of peak workload increased from 227
      (129) to 315 (195) seconds (p = 0.03). This was associated with a reduction in
      end-expiratory lung volume at peak exercise from 7.6 (1.6) to 7.2 (1.7) L (p =
      0.03). Using stepwise logistic regression analysis, a model containing changes in
      transfer factor and resting inspiratory capacity explained 81% of the variation
      in change in exercise time (p < 0.0001). The same variables were retained if the
      five patients with radiologic atelectasis were excluded from analysis. In a
      subgroup of patients in whom invasive measurements were performed, improvement in
      exercise capacity was associated with a reduction in lung compliance (r(2) =
      0.43; p = 0.03) and isotime esophageal pressure-time product (r(2) = 0.47; p =
      0.03). Endobronchial valve placement can improve lung volumes and gas transfer in
      patients with chronic obstructive pulmonary disease and prolong exercise time by
      reducing dynamic hyperinflation.

PMID- 15579726
TI  - How sensitive is the association between ozone and daily deaths to control for
      temperature?
AB  - RATIONALE: Air pollution has been associated with changes in daily mortality.
      OBJECTIVES: Generally, studies use Poisson regression, with complicated modeling
      strategies, to control for season and weather, raising concerns that the results
      may be sensitive to these modeling protocols. For studies of ozone, weather
      control is a particular problem because high ozone days are generally quite hot.
      METHODS: The case-crossover approach converts this problem into a case-control
      study, where the control for each person is the same person on a day near in
      time, when he or she did not die. This method controls for season and individual
      risk factors by matching. One can also choose the control day to have the same
      temperature as the event day. MEASUREMENTS: I have applied this approach to a
      study of more than 1 million deaths in 14 U.S. cities. MAIN RESULTS: I found
      that, with matching on temperature, a 10-ppb increase in maximum hourly ozone
      concentrations was associated with a 0.23% (95% confidence interval [CI] 0.01%,
      0.44%) increase in the risk of dying. This finding was indistinguishable from the
      risk when only matching on season and controlling for temperature with regression
      splines (0.19%; 95% CI 03%, 0.35%). Control for suspended particulate matter with
      an aerodynamic diameter of 10 mum or less (PM(10)) did not change this risk.
      However, the association was restricted to the warm months (0.37% increase; 95%
      CI 0.11%, 0.62%), with no effect in the cold months. CONCLUSIONS: The association
      between ozone and mortality risk is unlikely to be caused by confounding by
      temperature.

PMID- 15579727
TI  - Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung
      injury.
AB  - Although the pathogenic and genetic basis of acute lung injury (ALI) remains
      incompletely understood, the identification of novel ALI biomarkers holds promise
      for unique insights. Expression profiling in animal models of ALI (canine and
      murine) and human ALI detected significant expression of pre-B-cell colony
      enhancing factor (PBEF), a gene not previously associated with lung
      pathophysiology. These results were validated by real-time polymerase chain
      reaction and immunohistochemistry studies, with PBEF protein levels significantly
      increased in both bronchoalveolar lavage fluid and serum of ALI models and in
      cytokine- or cyclic stretch-activated lung microvascular endothelium. We
      genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized
      sample of white patients with sepsis-associated ALI, patients with severe sepsis,
      and healthy subjects and observed that carriers of the haplotype GC from SNPs T
      1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01
      19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant
      decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene
      assay. Together, these results strongly indicate that PBEF is a potential novel
      biomarker in ALI and demonstrate the successful application of robust genomic
      technologies in the identification of candidate genes in complex lung disease.

PMID- 15579728
TI  - Lipid peroxidation and 5-lipoxygenase activity in chronic obstructive pulmonary
      disease.
AB  - We studied the urinary excretion of the isoprostane 8-iso-prostaglandin F(2alpha)
      as an index of in vivo oxidant stress, and the production of leukotriene (LT)
      B(4) (LTB(4)) by neutrophils in subjects with chronic obstructive pulmonary
      disease (COPD) and normal subjects. Overnight urinary excretion of the
      isoprostane was significantly higher in patients with COPD than in control
      subjects, and LTB(4) production by challenge of neutrophils obtained from
      patients with COPD was also significantly higher than that observed in control
      neutrophils. Treatment with a standardized polyphenol extract caused a
      significant decrease in isoprostane excretion, accompanied by a statistically
      significant increase of Pa(O(2)). Furthermore, changes in FEV(1) significantly
      correlated with the changes in isoprostane urinary excretion observed from
      enrollment to the end of treatment. The results of this study suggest that
      enhanced oxidative stress in subjects with COPD is paralleled by the increased
      ability of neutrophils to synthesize the chemotactic factor LTB(4), and may
      ultimately contribute to the infiltration/activation of neutrophils into the
      airways of subjects with COPD. Antioxidant treatment in subjects with COPD is
      effective in reducing oxidant stress as shown by the decrease of urinary
      isoprostane, a reduction that correlates with the severity of the disease, as
      indicated by changes in Pa(O(2)) and FEV(1).

PMID- 15579729
TI  - Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic,
      and pathologic study.
AB  - RATIONALE: Clinicopathologic pulmonary manifestations associated with primary
      Sjogren's syndrome have yet to be reviewed in a large series since the
      recognition of nonspecific interstitial pneumonia (NSIP) as a distinct histologic
      pattern. OBJECTIVES: To determine clinical presentations, high-resolution
      computed tomographic (HRCT) and histologic findings of the lung disease
      associated with primary Sjogren's syndrome in the light of NSIP, and to analyze
      prognosis of the disease. METHODS: On the basis of 33 cases (31 surgical lung
      biopsies and 2 autopsies) collected consecutively from multiple centers, we have
      retrospectively evaluated clinical, radiologic, and pathologic manifestations of
      the disease. Prognostic factors were identified by univariate and multivariate
      analysis. MEASUREMENTS AND MAIN RESULTS: We found that NSIP was the most
      frequently seen histologic pattern (20 of 33 cases [61%], 19 fibrosing and 1
      cellular). Bronchiolar diseases and amyloid and malignant lymphoma were seen less
      frequently. HRCT-pathologic correlation resulted in a 94% positive predictive
      value of CT-NSIP pattern for pathologic diagnosis of NSIP, whereas the diagnostic
      value of HRCT was low (15%) with an HRCT pattern other than NSIP, data that may
      influence the decision to biopsy. The 5-year survival rate was 84% overall and
      83% in patients with NSIP. Multivariate analysis on all patients showed that low
      Pa(O(2)) (p = 0.02) and presence of microscopic honeycombing (p = 0.04) were
      independently associated with survival. Patients with NSIP showed lower vital
      capacity (mean +/- SD: 68.5 +/- 16.6%pred) than patients without NSIP (92.5 +/-
      18.6%pred; p < 0.001). CONCLUSION: Among a diversity of pulmonary lesions in
      primary Sjogren's syndrome, NSIP was the commonest histologic pattern and had a
      favorable prognosis.

PMID- 15579730
TI  - Chronically elevated endothelin levels reduce pulmonary vascular reactivity to
      nitric oxide.
AB  - Although local tissue activation of the endothelin (ET) system contributes to the
      development of pulmonary hypertension, the impact of isolated chronic plasma
      hyperendothelinemia on the pulmonary circulation is unknown. METHODS: Mini
      osmotic pumps were implanted in rats to deliver ET-1 during 7 or 28 days. After
      in vivo hemodynamics, the lungs were isolated to derive pressure-flow relations.
      Small pulmonary arteries ( approximately 250 microm) were mounted on an isometric
      myograph to study their reactivity. RESULTS: Plasma ET-1 approximately doubled (p
      < 0.05) after 7 and 28 days. Lung tissue ET-1 level increased fourfold after 7
      days (p < 0.001) but was no longer significantly elevated after 28 days. Right
      ventricular systolic pressure was unaffected. The pulmonary pressure-flow
      relation shifted upward with a steeper slope (p < 0.05) at 7 days, but not after
      28 days. Maximum dilatations to both acetylcholine (p < 0.01) and sodium
      nitroprusside (p < 0.001) were greatly reduced by approximately 50% after 28 days
      and were normalized by the addition of the nitric oxide synthase inhibitor L-NNA
      and the antioxidant N-acetyl-L-cysteine, respectively. CONCLUSION: Chronic
      hyperendothelinemia reduces the pulmonary vasodilator reserve in response to
      nitric oxide. Correction by an antioxidant and L-NNA suggests that this relates
      to increased production of reactive oxygen species, which may have clinical
      relevance for conditions associated with chronic increase of ET. Further studies
      are required to determine if, in the long term, this could contribute to the
      development of pulmonary hypertension.

PMID- 15579732
TI  - Adiposity signaling and biological defense against weight gain: absence of
      protection or central hormone resistance?
AB  - An abundant and compelling literature supports the existence of a homeostatic
      system that dynamically adjusts energy intake and energy expenditure to promote
      stability of body fat mass. In the context of this system, the ease with which
      many individuals gain weight is difficult to explain. Some have argued that
      energy homeostasis operates primarily to defend against weight loss and that,
      over the course of evolution, biological defense against weight gain was not
      selected for. According to this Absence of Protection model, obesity is seen as
      the natural result of living in an obesigenic environment. An alternative
      hypothesis, termed the Central Resistance model, proposes that under normal
      circumstances, the energy homeostasis system provides an effective defense
      against weight gain as well as weight loss and that common forms of obesity
      involve genetic or acquired defects (or interactions between them) that impair
      the function of this system. Here, we discuss these dichotomous possibilities
      within the context of current literature regarding energy homeostasis and suggest
      a strategy for distinguishing between them.

PMID- 15579733
TI  - Aromatase activity and bone homeostasis in men.
AB  - It is known that sex steroid hormones play an important role in the maintenance
      of bone mass in males as well as in females. Even though androgens are the major
      sex steroids in men, their primacy in regulating male skeletal remodeling has
      been increasingly questioned as direct and indirect evidence emerged suggesting
      that estrogens may also play a major role in male skeletal health. Recent data
      suggested that a threshold level of bioavailable estradiol is needed to prevent
      bone loss, and that with aging an increasing percentage of elderly men begin to
      fall below this level. The testes account for, at most, 15% of circulating
      estrogens in the male; the remaining 85% comes from peripheral aromatization of
      androgen precursors in different tissues, including bone. Human models of
      aromatase deficiency were the first to demonstrate the critical importance of the
      conversion of circulating androgens into estrogen in regulating male skeletal
      homeostasis. All four cases of aromatase-deficient men reported to date showed an
      identical skeletal phenotype, characterized by tall stature due to continued
      longitudinal growth, unfused epiphyses, high bone turnover, and osteopenia.
      Studies using knockout mice along with experimental observations in rats treated
      with an aromatase inhibitor provided useful information about the importance of
      aromatase in the male skeleton. Confirmatory evidence comes from recent
      interventional studies in adult men using aromatase inhibition, which confirmed
      that estrogens are critically important to the male skeleton by helping to
      control rates of bone remodeling. Intriguingly, common polymorphisms at the human
      aromatase (CYP19) gene have been associated with differences in aromatase
      activity, bone turnover, and rates of bone loss in elderly men, suggesting that
      variations in aromatase efficiency may also be relevant for skeletal homeostasis.
      Several additional mechanisms have been proposed in which aromatase activity
      could be modulated under certain circumstances in different tissues. Additional
      studies are needed to identify how these genetic, environmental, pathological,
      and pharmacological influences might modulate aromatase activity in vivo,
      increasing or reducing estrogen production in males and thereby affecting
      skeletal health.

PMID- 15579734
TI  - Somatostatin analogs for Graves' ophthalmopathy: do they bounce off like a rubber
      bullet?

PMID- 15579735
TI  - Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR)
      in thyroid-associated ophthalmopathy.
AB  - Several uncontrolled studies suggest octreotide is beneficial in thyroid
      associated ophthalmopathy (TAO); however, the natural tendency of TAO to improve
      mandates randomized, controlled trials. We report results of a double-blind,
      placebo-controlled trial of octreotide long-acting repeatable (LAR). Fifty
      euthyroid patients (11 males, 39 females; age 22-74 yr, median 50 yr) with active
      TAO [clinical activity score (CAS) > or =3, NOSPECS (no signs or symptoms; only
      signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal
      involvement; sight visual acuity reduction) 2a-5a] of median duration 0.9 yr
      received either 30 mg LAR or placebo every 4 wk for 16 wk; both groups then
      received 30 mg LAR for wk 16-32 and were followed up without treatment for a
      further 24 wk. Objective assessments included all individual parameters of TAO,
      CAS, and derived scores for soft tissue inflammation (STI) and ophthalmopathy
      index (OI). During wk 0-16 there was significant reduction in STI, subjective
      diplopia, and CAS in LAR-treated patients; STI and CAS were also reduced with
      placebo. The OI reduced by -1.12 in LAR (P = 0.0017) vs. -0.23 in placebo (P =
      0.33), giving a barely significant treatment effect by Wilcoxon (P = 0.043), but
      analysis of covariance failed to confirm this (P = 0.16). During wk 16-32 there
      was no significant change in OI in either group. The overall results (wk 0-32)
      showed reduction in STI and CAS in both groups. In this double-blind, placebo
      controlled trial, no significant therapeutic effect of octreotide LAR was seen in
      patients with moderately severe TAO. The improvements in both treated and placebo
      groups emphasize that the results of open studies must be viewed with caution.

PMID- 15579736
TI  - Defining the prevalence and incidence of androgen deficiency in aging men: where
      are the goal posts?

PMID- 15579737
TI  - Prevalence and incidence of androgen deficiency in middle-aged and older men:
      estimates from the Massachusetts Male Aging Study.
AB  - Little is known about the descriptive epidemiology of androgen deficiency. In
      this study, we sought to address this issue by providing estimates of the crude
      and age-specific prevalence and incidence rates of androgen deficiency in a
      randomly sampled population-based cohort of middle-aged and older men. Data on
      androgen deficiency (defined using both signs/symptoms plus total and calculated
      free testosterone) were available for n = 1691 (baseline) and n = 1087 (follow
      up) men from the Massachusetts Male Aging Study. Crude and age-specific
      prevalence and incidence rates were calculated. Based on these estimates,
      projections for the number of cases of androgen deficiency in the 40- to 69-yr
      old U.S. male population were computed. Estimates of the crude prevalence of
      androgen deficiency at baseline and follow-up were 6.0 and 12.3%, respectively.
      Prevalence increased significantly with age. From baseline age-specific
      prevalence data, it is estimated that there are approximately 2.4 million 40- to
      69-yr-old U.S. males with androgen deficiency. The crude incidence rate of
      androgen deficiency was 12.3 per 1,000 person-years, and the rate increased
      significantly (P < 0.0001) with age. Based on these incidence data, we can expect
      approximately 481,000 new cases of androgen deficiency per year in U.S. men 40-69
      yr old.

PMID- 15579738
TI  - Of mice and men: The tale of steroidogenic factor-1.

PMID- 15579739
TI  - Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a
      heterozygous inactive mutation of steroidogenic factor-1.
AB  - Steroidogenic factor-1 (SF-1) regulates multiple genes involved in the adrenal
      and gonadal development and in the biosynthesis of a variety of hormones,
      including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and
      gonadotropins. We identified a novel SF-1 mutation in a 27-yr-old Japanese
      patient with a 46,XY karyotype. Sequence analysis was performed for all the seven
      exons of SF-1, revealing a heterozygous single base pair deletion at exon 2
      (18delC) that is predicted to cause a frameshift at the sixth codon and resultant
      termination at the 74th codon. Functional studies showed that the mutation
      produced no demonstrable protein and had no transcription activity or dominant
      negative effect. Clinical features included small dysgenetic testes with vasa
      deferentia and epididymides, absent uterus, blind-ending vagina, clitoromegaly,
      and psychosexual disturbance. Endocrine studies showed normal adrenal function
      (cortisol response to ACTH stimulation, 13.4-->25.3 microg/dl) and primary
      hypogonadism (testosterone response to hCG stimulation, 0.57-->0.76 ng/ml;
      gonadotropin responses to GnRH stimulation: LH, 10-->59 mIU/ml; FSH, 36-->69
      mIU/ml), and urinary steroid hormone profile analysis indicated grossly normal
      steroidogenic enzyme activities. The results suggest that SF-1 haploinsufficiency
      can selectively impair testicular development and permit the biosynthesis of AMH
      and testosterone in dysgenetic testes and the production of gonadotropins in
      pituitary gonadotropes.

PMID- 15579740
TI  - Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating
      mutation of the calcium-sensing receptor.
AB  - Familial hypocalciuric hypercalcemia (FHH) and neonatal severe
      hyperparathyroidism (NSHPT) are consequent to inactivating mutations of the
      calcium-sensing receptor (CaR) gene. FHH is usually associated with heterozygous
      inactivating mutations of the CaR gene, whereas NSHPT is usually due to
      homozygous inactivation of the CaR gene. FHH is generally asymptomatic and is
      characterized by mild to moderate lifelong hypercalcemia, relative hypocalciuria,
      and normal intact PTH, whereas individuals with NSHPT frequently show life
      threatening hypercalcemia. In this study, we report a novel inactivating mutation
      of the CaR gene, identified in a 9-yr-old Brazilian girl who was found to be
      severely hypercalcemic during investigation of a 6-month history of headaches and
      vomits. Direct sequencing of the CaR gene from this patient showed a novel
      homozygous mutation (L13P) in exon 2. Functional characterization by
      intracellular calcium measurement by fluorometry showed that the mutant receptor
      had a dose-response curve shifted to the right relative to that of wild type. The
      proband's consanguineous parents, who had mild asymptomatic hypercalcemia, showed
      the same mutation in the heterozygous form. The mutation described in this study
      is the inactivating missense mutation present at the most N-terminal end among
      the known CaR missense mutations. This study reinforces the fact that patients
      with homozygous inactivation of the CaR gene may present with severe
      hypercalcemia in different phases of life.

PMID- 15579741
TI  - Phenotypic and molecular genetic aspects of pseudohypoparathyroidism type Ib in a
      Greek kindred: evidence for enhanced uric acid excretion due to parathyroid
      hormone resistance.
AB  - The predominant feature of pseudohypoparathyroidism (PHP) is renal resistance to
      PTH. Pseudohypoparathyroidism type Ia (PHP-Ia) is caused by maternally inherited
      heterozygous mutations in the GNAS exons encoding the alpha-subunit of the
      stimulatory G protein (Gsalpha). Besides PTH resistance, PHP-Ia patients have
      Albright's hereditary osteodystrophy and often display resistance to additional
      hormones. Patients with PHP-Ib lack features of Albright's hereditary
      osteodystrophy, and PTH resistance is associated with loss of methylation at the
      maternal GNAS exon A/B. Most individuals with the autosomal dominant form of PHP
      Ib have a 3-kb microdeletion within STX16 approximately 220 kb upstream of exon
      A/B. Here we report on the clinical and genetic aspects of a Greek PHP-Ib kindred
      with four affected members and three obligate carriers, who had the 3-kb deletion
      within STX16. Symptomatic hypocalcemia was present only in the proband, but PTH
      was elevated in all members who had inherited the 3-kb deletion maternally. In
      all affected family members, urinary phosphate excretion was normal, but 1,25
      dihydroxyvitamin D levels were diminished. These findings confirm previous data
      regarding patient to patient variation in disease severity for autosomal dominant
      PHP-Ib. Furthermore, affected individuals displayed hypouricemia with increased
      fractional excretion of uric acid, suggesting possible involvement of PTH in the
      renal handling of this metabolite.

PMID- 15579742
TI  - Oxyphil parathyroid adenoma: a malignant presentation of a benign disease.
AB  - Functioning parathyroid adenomas of the oxyphil cell type are rare, and the
      clinical characteristics of patients with these tumors have not been well
      defined. We describe two cases of severe primary hyperparathyroidism (PHPT)
      caused by benign oxyphil parathyroid adenomas. The patients' clinical
      presentations mimicked parathyroid carcinoma. Both had very large tumors
      associated with marked elevations in PTH and serum calcium levels. Skeletal
      manifestations were also atypical for benign PHPT, with severe osteoporosis in
      one patient and osteitis fibrosa cystica in the other. These cases also highlight
      the remarkable capacity of the skeleton to recover after successful
      parathyroidectomy, previously reported in other forms of severe PHPT. Bone
      mineral density improved dramatically 1 yr after parathyroidectomy, with
      increases of 51% at the lumbar spine, 36% at the total hip, and 11% at the distal
      one third radius. Most of the increases occurred in the first postoperative
      months. Consistent with this early and accelerated skeletal response, markers of
      bone turnover were increased 2 months after surgery and normalized by 8 months
      postoperatively. In patients with PHPT who present with severe or atypical
      clinical features, oxyphil adenoma should be considered.

PMID- 15579743
TI  - A novel circulating hormone of testis origin in humans.
AB  - Insulin-like factor 3 (INSL3) is a member of the relaxin-insulin family, and it
      is expressed in pre- and postnatal Leydig cells of the testis. This peptide
      affects testicular descent during embryonic development, and mutations in INSL3
      gene or its receptor LGR8 (leucine-rich repeat-containing G protein-coupled
      receptor 8)/GREAT (G protein-coupled receptor affecting testicular descent) cause
      cryptorchidism in humans. The expression of LGR8/GREAT in different tissues and
      the production of INSL3 also by adult-type Leydig cells suggest additional roles
      of this hormonal system in adulthood. In this preliminary report we performed the
      first analysis in humans of INSL3 using a novel RIA kit to measure INSL3
      concentrations in serum of normal men and with different testicular pathologies.
      The results show that INSL3 is circulating in adult men, and it is almost
      exclusively of testicular origin. Subjects with severe testicular damage, such as
      men with severe infertility, produce low amount of INSL3, and the concentrations
      of this hormone seem to reflect the functional status of the Leydig cells. In
      particular, INSL3 concentrations may be an even more sensitive marker of Leydig
      cell function than testosterone itself. Analysis of men treated with different
      combinations of hormones of the hypothalamus-pituitary-testis axis suggests that
      the production of INSL3 is related to LH in a manner similar to that of the LH
      testosterone axis.

PMID- 15579744
TI  - A single dose of the potent gonadotropin-releasing hormone antagonist acyline
      suppresses gonadotropins and testosterone for 2 weeks in healthy young men.
AB  - Acyline is a novel GnRH antagonist that reliably inhibits gonadotropins and
      testosterone (T) levels in men for 48 h after a single dose up to 75 microg/kg.
      In this study we examined gonadotropin and T levels in 28 healthy young men
      administered acyline as single doses of 150 or 300 microg/kg or serial injections
      of 75 microg/kg. A single 300 microg/kg dose of acyline suppressed gonadotropins
      and T to castrate levels for 15 d (baseline, 21.1 +/- 3.1; nadir, 1.95 +/- 0.4
      nmol/liter; mean +/- sem; P < 0.05). Serum acyline levels peaked 90 min after the
      injection of 300 microg/kg acyline to a maximum concentration of 112.4 +/- 18
      ng/ml (n = 7; t(1/2) = 4.9 d). Injections of 75 microg/kg acyline every 2 d for
      five doses suppressed gonadotropins for more than 20 d (nadir T, 1.06 +/- 0.17
      nmol/liter; P < 0.05 compared with baseline). Adverse events were mild and
      included erythema and pruritus at the injection site. Acyline, therefore, is one
      of the most potent peptide GnRH antagonists studied to date with minimal adverse
      events. A twice monthly injection of acyline could be used as a potent suppressor
      of the GnRH axis to advance the development of a hormonal male contraceptive or
      for treatment of hormonally dependent disease.

PMID- 15579745
TI  - A comparison of echocardiography and magnetic resonance imaging in cardiovascular
      screening of adults with Turner syndrome.
AB  - The high mortality rate from aortic dissection of women with Turner syndrome (TS)
      achieving ovum donation pregnancies has highlighted the need for a refinement of
      cardiac screening protocols. Echocardiography and magnetic resonance imaging
      (MRI) are used to assess the risk factors, aortic root dilatation, bicuspid
      aortic valve, and coarctation, but the relative merits of each modality are
      unclear. Cardiovascular screening was performed in 128 unselected women with TS
      (mean age +/- SD, 31.1 +/- 8.5 yr) using echocardiography (n = 120) and MRI (n =
      115) and in 36 age-matched normal control women. Clinical history, anthropometric
      measurements, blood pressure, and metabolic parameters were recorded.
      Echocardiography was normal in 53% of women with TS; MRI was normal in 34%.
      Aortic root dilatation was identified in 16% of women by echocardiography, 33% on
      MRI criteria, and 7% by both modalities. Height-adjusted echocardiographic aortic
      root dimensions were greater in TS than controls (2.90 vs. 2.62 cm; P = 0.010).
      Bicuspid aortic valve and increasing age were associated with greater aortic
      dimensions; the latter effect was more marked in TS than controls. On MRI,
      ascending aortic diameter was greater in TS than control women (2.83 vs. 2.52 cm;
      P = 0.029), but descending aortic diameter and ascending/descending aortic ratio
      were not, because these may be affected by the presence of coarctation. The two
      techniques are complementary and identify different aspects of cardiovascular
      pathology. Ascending/descending ratio on MRI circumvents issues of stature, but
      may be influenced by descending aortic abnormalities. We present reference ranges
      for absolute aortic dimensions in a TS population to aid future interpretation of
      these measurements.

PMID- 15579746
TI  - Effects of atorvastatin on the clearance of triglyceride-rich lipoproteins in
      familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) patients have an impaired catabolism of
      postprandial triglyceride (TG)-rich lipoproteins (TRLs). We investigated whether
      atorvastatin corrects the delayed clearance of large TRLs in FCHL by evaluating
      the acute clearance of Intralipid (10%) and TRLs after oral fat-loading tests.
      Sixteen matched controls were included. Atorvastatin reduced fasting plasma TG
      (from 3.6 +/- 0.4 to 2.5 +/- 0.3 mM; mean +/- SEM) without major effects on
      fasting apolipoprotein B48 (apoB48) and apoB100 in large TRLs. Atorvastatin
      significantly reduced fasting intermediate density lipoprotein (Svedberg
      flotation, 12-20)-apoB100 concentrations. After Intralipid, TG in plasma and TRL
      showed similar kinetics in FCHL before and after atorvastatin treatment, although
      compared with controls, the clearance of large TRLs was only significantly slower
      in untreated FCHL, suggesting an improvement by atorvastatin. Investigated with
      oral fat-loading tests, the clearance of very low density lipoprotein (Sf20-60)
      apoB100 improved by 24%, without major changes in the other fractions. The most
      striking effects of atorvastatin on postprandial lipemia in FCHL were on hepatic
      TRL, without major improvements on intestinal TRLs. Fasting plasma TG should be
      reduced more aggressively in FCHL to overcome the lipolytic disturbance causing
      delayed clearance of postprandial TRLs.

PMID- 15579747
TI  - Long-term follow-up of thyroid function in patients who received bone marrow
      transplantation during childhood and adolescence.
AB  - An increasing number of long-term surviving bone marrow transplant (BMT)
      recipients have recovered from their primary disease but are at risk of
      developing failure of endocrine organs. We investigated 147 patients who
      underwent allogeneic BMT. Thyroid function was evaluated by serial measurement of
      basal TSH and free T4 levels as well as by TRH provocative test. Thyroid
      ultrasound examination was performed for evaluation of thyroid tumor after BMT.
      Five patients were found to have overt thyroid dysfunction (hypothyroidism in
      four patients and hyperthyroidism in one patient). Twenty-three patients in the
      under 9-yr-old group at BMT and 16 patients in the over 10-yr-old group at BMT
      had subclinical compensated hypothyroidism. Younger age at BMT was the strongest
      factor for developing thyroid dysfunction, compared with older age (P < 0.001).
      Only in patients with subclinical compensated hypothyroidism did median basal and
      peak TSH increase to the upper half of the normal range by 8 yr after BMT and
      then returned slightly to the middle of the normal range spontaneously. These
      results suggest that thyroid dysfunction in long-term BMT survivors depends on
      age at BMT, with a greater risk among younger patients, indicating the need for
      life-long surveillance.

PMID- 15579748
TI  - Posterior pituitary dysfunction after traumatic brain injury.
AB  - Disorders of water balance are well recognized after traumatic brain injury
      (TBI), but there are no reliable data on their true prevalence in post-TBI
      patients. We aimed to evaluate the prevalence of posterior pituitary dysfunction
      in a large cohort of survivors of TBI. One hundred two consecutive patients (85
      males) who suffered severe or moderate TBI were evaluated for diabetes insipidus
      (DI) at a median of 17 months (range 6-36 months) after the event, using the 8-h
      water deprivation test (WDT). Their results were compared against normative data
      obtained from 27 matched, healthy controls. Patients' medical records were
      retrospectively reviewed for the presence of abnormalities of salt and water
      balance in the immediate post-TBI period. Twenty-two patients (21.6%) developed
      DI in the immediate post-TBI period (acute DI group), of whom five had abnormal
      WDT on later testing. In total, seven patients (6.9%) had abnormal WDT (permanent
      DI group), five of whom had partial DI. Patients in the acute and permanent DI
      groups were more likely to have more severe TBI, compared with the rest of the
      cohort (P < 0.05). In the immediate post-TBI period, 13 patients (12.9%) had
      syndrome of inappropriate secretion of antidiuretic hormone, which persisted in
      one patient, and one other patient developed cerebral salt wasting. Diabetes
      insipidus and syndrome of inappropriate secretion of antidiuretic hormone were
      common in the immediate post-TBI period. Permanent DI was present in 6.9% of
      patients who survived severe or moderate TBI, which is higher than traditionally
      thought. Identification of patients with partial posttraumatic DI is important
      because appropriate treatment may reduce morbidity and optimize the potential for
      recovery.

PMID- 15579749
TI  - Relationship between ghrelin and energy expenditure in healthy young women.
AB  - Ghrelin is a novel peptide that has been isolated from human and rat stomach
      tissues. Despite its known stimulatory effects on appetite and eating behavior,
      little information is available regarding its relationship with energy
      expenditure in normal-weight humans. To address this issue, we examined the
      relationship between serum ghrelin and resting metabolic rate (RMR), the thermic
      effect of food (TEF), fasting and postprandial respiratory quotient, physical
      activity level, peak aerobic capacity (VO(2 peak)), energy intake, and
      psychological measures of feeding behavior. We recruited 65 young healthy women
      and determined RMR and TEF by indirect calorimetry after a 12-h fast. Physical
      activity was determined by a leisure time physical activity questionnaire; VO(2
      peak) was determined by bicycle ergometer test to exhaustion; energy intake was
      determined by a 24-h dietary recall; and food behavior was determined by a three
      factor eating questionnaire. Our cohort showed a broad range of body mass index
      (range, 16.8-28.3 kg/m2), RMR (range, 820-1550 kcal/d), TEF (range, 74.4-136.5
      kcal/d), and percent body fat (range, 14.0-37.7%). We noted significant inverse
      correlations between ghrelin and RMR (r = -0.350, P = 0.004) and TEF (r = -0.396,
      P = 0.001). These inverse correlations persisted after statistical control for
      both fat-free mass and fat mass (ghrelin vs. RMR partial, r = -0.284, P = 0.024;
      and ghrelin vs. TEF partial, r = -0.329, P = 0.01) and insulin levels (ghrelin
      vs. RMR partial, r = -0.255, P = 0.046; and ghrelin vs. TEF partial, r = -0.287,
      P = 0.024) using partial correlation analysis. We also observed a significant
      inverse correlation between ghrelin and daily caloric intake (r = -0.266, P =
      0.032), but ghrelin levels were not significantly correlated with fasting (r = 
      0.002), postprandial respiratory quotient (r = -0.016), leisure time physical
      activity (r = 0.104), VO(2 peak) (r = 0.138), dietary disinhibition (r = -0.071),
      dietary restraint (r = 0.051), or feeling of general hunger (r = -0.028). These
      results suggest that higher levels of ghrelin are associated with low levels of
      resting and postprandial thermogenesis, which is independent of individual
      differences in fat-free mass and fat mass. Although speculative, serum ghrelin
      may play a role in the regulation of energy homeostasis by acting as a hormonal
      marker of increased energy efficiency.

PMID- 15579750
TI  - The severity of growth hormone deficiency correlates with the severity of cardiac
      impairment in 100 adult patients with hypopituitarism: an observational, case
      control study.
AB  - In 100 patients with hypopituitarism and 80 sex- and age-matched healthy
      subjects, we correlated the severity of cardiac impairment to the severity of GH
      deficiency (GHD). By the GH peak after arginine plus GHRH test (normal > 16.5
      microg/liter), the patients were classified as severe GHD (n = 56), partial GHD
      (n = 27), and non-GHD (n = 17). Compared with controls, decreased left
      ventricular ejection fraction at rest was found only in severe GHD patients (55.0
      +/- 8.8 vs. 63.4 +/- 4.5%, P < 0.001); decreased left ventricular ejection
      fraction response on effort in severe (-4.6 +/- 17.4 vs. 15.2 +/- 9.1%, P <
      0.001) and partial GHD patients (3.6 +/- 6.6 vs. 14.6 +/- 8.3%, P < 0.001);
      decreased diastolic filling at rest in severe (2.53 +/- 0.68 vs. 3.01 +/- 0.48
      end-diastolic volume per second, P < 0.001) and partial GHD (2.61 +/- 0.45 vs.
      2.89 +/- 0.54 end-diastolic volume per second, P = 0.004) patients; and decreased
      exercise duration and capacity in all the patient groups. A normal systolic
      performance on effort was found in 21.4% of severe GHD, 55.6% of partial GHD, all
      non-GHD, and 93.7% of controls. A normal diastolic filling at rest was found in
      57.1% of severe GHD, 74.1% of partial GHD, 76.5% of non-GHD, and 90% of controls.
      In conclusion, cardiac performance is correlated with the GH status because
      significant impairment was found in patients with severe and partial GHD but not
      in non-GHD hypopituitary patients.

PMID- 15579751
TI  - Identification of patients with Cushing's disease with negative pituitary
      adrenocorticotropin gradients during inferior petrosal sinus sampling: prolactin
      as an index of pituitary venous effluent.
AB  - Inferior petrosal sinus sampling for ACTH differentiates pituitary ACTH-dependent
      Cushing's (CD) from the ectopic ACTH syndrome (EAS). Petrosal sinus to peripheral
      (IPS:P) ACTH ratios greater than 2.0 in the basal state or a peak greater than
      3.0 after CRH are diagnostic of CD. However, false-negative rates of 1-10% have
      been reported. We report three patients with features of CD with peak IPS:P ACTH
      ratios less than 3.0 after CRH suggesting EAS. We compared IPS:P prolactin (PRL)
      as an index of pituitary venous effluent in these three index cases with 44
      patients with CD and five with EAS. The dominant basal IPS:P PRL ratio was
      greater than 1.8 in all 49 patients but was less than 1.2 in the three index
      cases. The IPS:P ACTH ratio normalized to IPS:P PRL was greater than 0.8 in all
      CD patients but was less than 0.6 in EAS patients. The IPS:P ACTH ratios
      normalized to IPS:P PRL were greater than 1.2 in the index cases, which was
      similar to those with CD. The three index cases had clinical and biochemical
      remissions after pituitary surgery.PRL is an index of pituitary venous effluent
      during inferior petrosal sinus sampling in patients with CD who fail to have a
      peak IPS:P ACTH ratio greater than 3.0 after CRH. IPS:P PRL should be measured
      when results indicate EAS.

PMID- 15579752
TI  - Factors influencing the basal and recombinant human thyrotropin-stimulated serum
      thyroglobulin in patients with metastatic thyroid carcinoma.
AB  - The serum thyroglobulin (Tg) level is the most sensitive marker for detecting
      residual thyroid carcinoma. We hypothesized that the basal and TSH-stimulated Tg
      levels in patients with metastatic thyroid carcinoma would reflect tumor volume,
      histological subtype, and location of metastatic lesions. A retrospective review
      of 417 thyroid cancer survivors undergoing evaluation for residual disease with
      the assistance of recombinant human TSH (rhTSH) was performed. In 169 patients
      with metastatic disease, we found that the basal Tg level directly correlated
      with the number of lesions, and that it was highest in patients with follicular
      and lowest in those with papillary thyroid carcinoma. The basal Tg level was
      highest in patients with bone metastases and lowest in those with cervical
      metastases. The fold increase in the serum Tg after rhTSH treatment was highest
      in papillary thyroid carcinoma and lowest in Hurthle cell carcinoma. The fold
      increase in Tg was not influenced by tumor volume or by the site of metastatic
      lesions. Multivariate analysis showed multiple interactions between factors, but
      did not identify one factor that significantly influenced basal Tg or fold
      increase. We conclude that the location and volume of metastases influence basal
      Tg, but not its responsiveness to rhTSH, whereas the histological type of
      carcinoma influences both basal Tg and responsiveness to rhTSH.

PMID- 15579753
TI  - Whole body protein breakdown is less inhibited by insulin, but still responsive
      to amino acid, in nondiabetic elderly subjects.
AB  - Responses of whole body glucose disposal (GDR) and protein breakdown (PB) to
      physiological insulin levels are altered in nondiabetic elderly subjects. Amino
      acids enhance inhibition of PB by insulin in young subjects. We hypothesized that
      addition of amino acid to insulin may improve the defect in PB regulation by
      insulin in elderly people. Therefore, we investigated the effect of
      hyperinsulinemia combined to either euaminoacidemia (EuAA) or hyperaminoacidemia
      (HyperAA) on GDR and PB, using isotopic dilution of D-[6,6-2H2]glucose and L-[1
      13C]leucine, in young (mean +/- SEM, 24.4 +/- 0.8 yr) and elderly (70.2 +/- 0.7
      yr) subjects. GDR was lower in elderly than in young subjects in all situations
      (P < 0.05). Despite a greater inhibition with HyperAA, PB was less inhibited in
      elderly than in young subjects during both clamps (ratio between change over
      basal PB and change over basal insulinemia, -0.014 +/- 0.002 vs. -0.024 +/- 0.003
      in EuAA and -0.022 +/- 0.002 vs. -0.036 +/- 0.003 micromol/ml.microU/kg fat-free
      mass.min in HyperAA; elderly vs. young, P < 0.05). In conclusion, in nondiabetic
      elderly subjects, PB is less inhibited by insulin with either basal or high amino
      acid concentrations. Addition of amino acid potentiates insulin-induced
      suppression of PB in both groups to the same extent, suggesting a specific
      dysregulation of PB by insulin with age.

PMID- 15579754
TI  - Estrogens are essential for male pubertal periosteal bone expansion.
AB  - The skeletal response to estrogen therapy was studied in a 17-yr-old boy with
      congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol
      valeriate/d from age 17 until 20 yr) normalized total and free testosterone and
      reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed
      areal bone mineral density (BMD) of the lumbar spine and femoral neck increased
      significantly (by 23% and 14%, respectively), but peripheral quantitative
      computed tomography at the ultradistal radius revealed no gain of either
      trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven
      by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and
      especially cross-sectional area of the radius (+46%) and cortical thickness
      (+12%), as measured by peripheral quantitative computed tomography, increased
      markedly during estrogen treatment. These findings demonstrate that androgens
      alone are insufficient, whereas estrogens are essential for the process of
      pubertal periosteal bone expansion typically associated with the male bone
      phenotype.

PMID- 15579755
TI  - Effects of oral administration of androstenedione on plasma androgens in young
      women using hormonal contraception.
AB  - Androstenedione as a dietary supplement has been targeted at the sporting
      community, but there are limited data regarding its effects on plasma androgens
      in young women. A double-blind, cross-over study was undertaken involving 10
      women (20-32 yr) using hormonal contraception. Because contamination of
      supplements has been reported, an in-house oral formulation was prepared
      containing purified androstenedione, the control being lactose only. After oral
      administration of a single dose of androstenedione (100 mg), blood was collected
      frequently up to 8 h and at 24 h. Maximum plasma androgen concentrations observed
      between volunteers were well above the upper limit of reference ranges for women,
      being 121-346 nmol/liter for androstenedione, 14-54 nmol/liter for testosterone
      (T), 11-32 nmol/liter for 5alpha-dihydrotestosterone, and 23-90 nmol/liter for
      3alpha-androstanediol glucuronide. The free androgen index and T concentration
      changed in a similar manner. The mean change in area under the plasma
      concentration-time curve (0-24 h), compared with control data were:
      androstenedione approximately 7-fold, T approximately 16-fold, 5alpha
      dihydrotestosterone approximately 9-fold, and 3alpha-androstanediol glucuronide
      approximately 5-fold; the mean conversion ratio of androstenedione to T was 12.5%
      (range 7.8-21.6%). Increases in T area under the plasma concentration-time curve
      were correlated with SHBG concentration (r = 0.80; P = 0.005). Formulation
      characteristics and SHBG levels appear to be important factors when considering
      plasma androgen increases after acute androstenedione administration.

PMID- 15579756
TI  - Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic
      diseases in a general population: the Tromso Study.
AB  - The role played by endogenous hormones in many diseases makes it important to
      understand factors influencing their levels. This study examined the distribution
      of total and free estradiol, FSH, and dehydroepiandrosterone sulfate (DHEAS) by
      age and sex and associations of these hormones with body mass index (BMI),
      lifestyle factors, and chronic diseases. Plasma samples taken from 1555 men and
      1952 women 25-84 yr of age in 1994-1995 Tromso Study were analyzed in 2001. Total
      estradiol increased with age among men (P < 0.001), with or without adjustment
      for BMI and lifestyle factors. FSH increased with age both in men (P < 0.001) as
      well as pre- (P < 0.001) and postmenopausal women (P = 0.01) after similar
      adjustment, and DHEAS decreased with age in both sexes (P < 0.001). With
      increasing BMI, free estradiol increased in men (P = 0.004), total and free
      estradiol increased in postmenopausal women (P < 0.001), and FSH decreased in men
      (P = 0.03) and postmenopausal women (P < 0.001). Men with chronic diseases had
      lower levels of DHEAS, compared with healthy men (P < 0.001). Smokers had higher
      DHEAS levels than nonsmokers. Further studies are needed to confirm these
      hormonal changes with age and disease.

PMID- 15579757
TI  - Rosiglitazone, but not glyburide, reduces circulating proinsulin and the
      proinsulin:insulin ratio in type 2 diabetes.
AB  - An elevation in the ratio of proinsulin (PI) to immunoreactive insulin (IRI) is
      inversely related to beta-cell function in type 2 diabetes, and increased PI is
      an independent risk factor for coronary heart disease. An objective of the
      present studies was to assess the effects of the thiazolidinedione insulin
      sensitizer, rosiglitazone, on indirect markers of beta-cell function and
      cardiovascular risk in people with type 2 diabetes by measuring plasma PI and the
      PI:IRI ratio. Parameters of insulin processing, including plasma PI and PI:IRI
      ratios, were determined in type 2 diabetes patients enrolled in two randomized
      double-blind studies comparing the effects of rosiglitazone (4 or 8 mg/d) with
      placebo (study 1, 26-wk treatment) or the sulfonylurea glyburide (study 2, 52-wk
      treatment). Treatment with rosiglitazone for 26 wk (study 1) produced significant
      dose-dependent decreases in both plasma PI concentrations (18-29%) and the PI:IRI
      ratio compared with baseline (7-14%) and placebo (19-29%) (P < 0.001). A
      significant increase in the PI:IRI ratio in placebo-treated patients occurred (P
      < 0.001). In study 2, rosiglitazone also significantly reduced both plasma PI and
      the PI:IRI ratio compared with baseline (P < 0.001). In contrast, glyburide
      significantly increased both plasma PI (45%; P < 0.001) and the PI:IRI ratio
      (10%) (P < 0.05 vs. baseline). These results show that rosiglitazone and
      glyburide have differential effects on absolute PI levels and the PI:IRI ratio in
      people with type 2 diabetes.

PMID- 15579758
TI  - Attention deficit and hyperactivity disorders in the offspring of mothers exposed
      to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder
      in developed countries.
AB  - Over a period of almost 10 yr, we carried out a prospective study of the
      neuropsychological development of the offspring of 16 women from a moderately
      iodine-deficient area (area A) and of 11 control women from a marginally iodine
      sufficient area (area B) whose thyroid function had been monitored during early
      gestation. Attention deficit and hyperactivity disorder (ADHD) was diagnosed in
      11 of 16 area A children (68.7%) but in none from area B. Total intelligence
      quotient score was lower in area A than in area B children (92.1 +/- 7.8 vs. 110
      +/- 10) and in ADHD children when compared with both non-ADHD children from the
      same area and control children (88.0 +/- 6.9 vs. 99.0 +/- 2.0 and 110 +/- 10,
      respectively). Seven of 11 ADHD children (63.6%) were born to the seven of eight
      area A mothers who became hypothyroxinemic at early gestation, whereas only one
      of five non-ADHD children was born to a woman who was hypothyroxinemic at 20 wk
      of gestation. So far, a similar prevalence of ADHD has been reported only in
      children with generalized resistance to thyroid hormones. This might suggest a
      common ADHD pathogenetic mechanism consisting either of reduced sensitivity of
      the nuclear receptors to thyroid hormone (generalized resistance to thyroid
      hormones) or reduced availability of intracellular T3 for nuclear receptor
      binding. The latter would be the ultimate consequence of maternal
      hypothyroxinemia (due to iodine deficiency), resulting in a critical reduction of
      the source of the intracellular T3 available to the developing fetal brain.

PMID- 15579759
TI  - The relationship between C-reactive protein and carotid intima-media wall
      thickness in middle-aged women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is associated with premature carotid
      atherosclerosis. C-Reactive protein (CRP) has been implicated as a vascular
      disease risk factor. The objective of this study was to determine whether
      elevated CRP is associated with increased carotid intima-media wall thickness
      (IMT) in PCOS women. Forty-seven PCOS patients and 59 similarly aged controls
      were screened for cardiovascular risk factors and concurrently underwent carotid
      ultrasonography (1996-1999). The main outcome measure was carotid IMT. CRP was
      significantly higher in PCOS patients than in controls (3.4 vs. 2.1 mg/dl; P =
      0.002). In regression modeling, PCOS associated with IMT independently of CRP and
      age (P = 0.019). Body mass index reduced the association of PCOS and CRP with IMT
      and was also associated with IMT (P = 0.029). The CRP-IMT relationship was
      attenuated when either insulin or visceral fat was included in the PCOS-age-CRP
      model (P = 0.197 and P = 0.550, respectively). PCOS remained associated with IMT
      independent of insulin (P = 0.033) or visceral fat (P = 0.040). CRP does not
      appreciably mediate the effect of PCOS on IMT. Obesity partially explained the
      influence of PCOS and CRP on IMT. The effect of body mass index on the PCOS-IMT
      relationship was not completely determined by hyperinsulinemia or visceral fat,
      and might be mediated by other aspects of PCOS-related adiposity.

PMID- 15579760
TI  - Efficacy and safety of pioglitazone versus metformin in patients with type 2
      diabetes mellitus: a double-blind, randomized trial.
AB  - Pioglitazone increases the insulin sensitivity of peripheral tissues and may
      provide an alternative first-line treatment for type 2 diabetes. This study
      compared metabolic control in drug-naive type 2 diabetes patients given either
      pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly
      controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%;
      normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d)
      or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose
      (FPG), insulin levels, total cholesterol (TC), high density lipoprotein
      cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free
      fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c
      decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%).
      Significantly greater mean reductions in FPG were observed in the pioglitazone
      group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2
      mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were
      more pronounced with pioglitazone. Although low density lipoprotein cholesterol
      and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly
      with both treatments. The urinary albumin/creatinine ratio was reduced by 19%
      with pioglitazone treatment, but remained unchanged with metformin therapy (-1%;
      P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone
      group and a decrease of 2.5 kg in the metformin group. The overall frequency of
      adverse events was similar between treatment groups, but adverse event profiles
      were different between treatment groups. HbA1c reduction is similar after
      pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids,
      and adverse effects between the two compounds may influence decision-making in
      individual prescribers.

PMID- 15579761
TI  - Smoke exposure is associated with a lower prevalence of serum thyroid
      autoantibodies and thyrotropin concentration elevation and a higher prevalence of
      mild thyrotropin concentration suppression in the third National Health and
      Nutrition Examination Survey (NHANES III).
AB  - Few modifiable exposures influencing autoimmune thyroid disease have been
      identified. Studies evaluating cigarette smoke and thyroid disorders have yielded
      conflicting results. The relationship between smoking and thyroid abnormalities
      was evaluated in the 1988-1994 Third National Health and Nutrition Examination
      Survey (NHANES III), a cross-sectional study that used a complex, multistage,
      stratified, clustered sampling approach to reflect the entire
      noninstitutionalized United States population. Among 18,148 persons who underwent
      thyroid testing, data regarding age, gender, iodine status, smoke exposure, and
      thyroid tests were complete for 16,046 persons. After excluding those taking
      thyroid-altering medications, 15,592 remaining subjects were analyzed. Subjects
      with serum cotinine levels greater than 15 ng/ml were classified as smokers.
      Outcome measures included the presence of 1) antithyroperoxidase antibody levels
      of 0.5 IU/ml or more or antithyroglobulin antibody levels of 1.0 IU/ml or more,
      2) TSH concentration greater than 4.5 mU/liter, 3) TSH concentration less than
      0.1 mU/liter, and 4) TSH concentration of 0.1-0.4 mU/liter. Fewer smokers (11%,
      95% confidence interval (CI) = [10-13%]) had thyroid autoantibodies compared with
      nonsmokers (18%, 95% CI = [17-19%]). Prevalence in smokers after adjustment for
      age, gender, race-ethnicity, and iodine status was 13%, 95% CI = [12-15%]. Fewer
      smokers (2.6%, 95% CI = [2.0-3.2%]) had elevated TSH compared with nonsmokers
      (5.5%, 95% CI = [4.7-6.3%]). The adjusted rate in smokers was 3.4%, 95% CI = [2.6
      4.3%]). Among persons with thyroid autoantibodies, smokers had 40% lower odds of
      TSH elevation compared with nonsmokers (adjusted odds ratio [95% CI] = 0.6 [0.4
      0.97]). Among persons without TSH elevation, smoke exposure was associated with
      200% greater odds of low normal TSH 0.1-0.4 mU/liter (adjusted odds ratio [95%
      CI] = 2.0 [1.3-2.9]). Smoking appears to be negatively associated with
      serological evidence of thyroid autoimmunity and hypothyroidism and positively
      associated with mild TSH decreases. Eliminating smoke exposure may help prevent
      the low normal TSH measurements that are characteristic of mild hyperthyroidism.
      Understanding the underlying mechanism could help identify potential pathways for
      the prevention of autoimmune thyroid disease.

PMID- 15579762
TI  - Elevated urine pregnanetriolone definitively establishes the diagnosis of
      classical 21-hydroxylase deficiency in term and preterm neonates.
AB  - Elevated blood 17alpha-hydroxyprogesterone (17OHP) level, although widely used
      for the screening of classical 21-hydroxylase deficiency (21OHD) in neonates, has
      frequently been found in some neonates without classical 21OHD, particularly
      preterm neonates. We studied the diagnostic value of the metabolite of 21
      deoxycortisol (pregnanetriolone, Ptl) and the metabolite of 17OHP (pregnanetriol,
      PT) in identifying 21OHD in term and preterm neonates with elevated blood 17OHP
      on the newborn screening. Spot urine samples from 59 classical 21OHD neonates (50
      term, 9 preterm), 83 neonates without 21OHD having transiently elevated blood
      17OHP (non-21OHD) (49 term, 34 preterm), and 62 control term neonates were
      studied using gas chromatography/mass spectrometry in selected ion monitoring
      analysis for Ptl, PT, 5beta-tetrahydrocortisone (betaTHE), and 5alpha
      tetrahydrocortisone (alphaTHE). Ptl and Ptl/(betaTHE+alphaTHE) showed no overlap
      between 21OHD and non-21OHD, and 21OHD and controls, respectively (Ptl was 0.46
      124 mg/g creatinine in 21OHD term, 0.80-26.9 mg/g creatinine in 21OHD preterm, <
      or = 0.08 mg/g creatinine in non-21OHD term, < or =0.06 mg/g creatinine in non
      21OHD preterm, and < or = 0.07 mg/g creatinine in controls). PT and
      PT/(betaTHE+alphaTHE) showed significant overlap between 21OHD and non-21OHD. The
      above data indicate that spot urine Ptl is a highly specific marker of 21OHD with
      a cutoff value of 0.1 mg/g creatinine, yielding an unambiguous separation between
      21OHD and non-21OHD in term and preterm neonates.

PMID- 15579763
TI  - Scintigraphy for risk stratification of iodine-induced thyrotoxicosis in patients
      receiving contrast agent for coronary angiography: a prospective study of
      patients with low thyrotropin.
AB  - The risk of iodine-induced thyrotoxicosis in euthyroid patients receiving iodine
      containing contrast agents is known to be low, but data on this risk in patients
      with latent hyperthyroidism are scarce. We investigated the role of thyroid
      scintigraphy using Tc-99m preceding the application of iodine-containing contrast
      material to estimate the risk of iodine-induced thyrotoxicosis in patients with
      low levels of TSH. In a prospective study on 91 patients, thyroid scintigraphy
      was performed before coronary angiography (CA). In patients with technetium
      thyroid uptake (TCTU) less than 1%, CA was done without prophylactic drugs (n =
      56). Patients with TCTU greater than 1% were treated either with 900 mg of
      perchlorate or, depending on the autonomous volume, combined with 20 to 60 mg
      thiamazole. In the 56 patients with TCTU less than 1%, no case of iodine-induced
      hyperthyroidism occurred within 4 wk after CA. In the patients who received
      prophylactic drugs, two cases of mild thyrotoxicosis were observed. Our data
      suggest that in patients with low levels of TSH, the risk of hyperthyroidism
      after application of iodine-containing contrast media is negligible if TCTU is
      less than 1%. In these patients, CA can be performed without administration of
      prophylactic drugs.

PMID- 15579764
TI  - Raloxifene modulates interleukin-6 and tumor necrosis factor-alpha synthesis in
      vivo: results from a pilot clinical study.
AB  - Raloxifene (RAL), a selective estrogen receptor modulator, is indicated for the
      prevention and treatment of postmenopausal osteoporosis. RAL, by decreasing bone
      turnover, prevents bone loss and microarchitecture damage, reducing the incidence
      of osteoporotic fractures. Our previous in vitro data demonstrated that RAL
      modulates osteoclast activity by, at least in part, an IL-6- and TNF-alpha
      dependent mechanism. In this study we evaluated the effects of RAL treatment (60
      mg/d) on circulating levels of these cytokines in 14 postmenopausal women with
      osteoporosis. Lumbar bone density (determined by dual energy x-ray
      absorptiometry) and IL-6 and TNF-alpha levels were measured before and after 6
      and 24 months of therapy. After 24 months, RAL increased bone density. IL-6 and
      TNF-alpha expression, elevated before treatment, significantly decreased (50% and
      30%, respectively) after 6 months. This effect was sustained up to the end of the
      treatment (75% and 35%, respectively). Thus, our data show that RAL can modulate
      circulating levels of cytokines involved in osteoclastogenesis and bone
      resorption, suggesting that modulation of soluble factors could play a pivotal
      role in the mechanisms of the osteoprotective effect of RAL.

PMID- 15579765
TI  - Growth hormone therapy in children after cranial/craniospinal radiation therapy:
      sexually dimorphic outcomes.
AB  - Radiation therapy (RT) to the craniospinal region in childhood affects final
      height. The use of GH treatment (GHRx) in children after cranial or craniospinal
      RT results in variable improvement in final height. Nineteen children (12 males
      and 7 females) with tumors of the head, treated with cranial or craniospinal RT
      and subsequently with GHRx, were assessed for final height. Two outcome measures
      of efficacy of GHRx were used: Y1 = final height SD score (SDS) corrected for
      genetic potential, using midparental sex-adjusted target height (SATH) SDS, and
      Y2 = change in height SDS from predicted final height SDS pre-GHRx to actual
      final height SDS post-GHRx. The median age at diagnosis was 5.4 yr, the median RT
      to the hypothalamic-pituitary axis was 40 Gy, the median spinal RT dose in 13 of
      19 of the subjects treated was 36 Gy, and the median years post-RT to GHRx was
      4.8 yr. Adjuvant chemotherapy was used in 12 of 19 patients. All but one (optic
      glioma) had a lesion anatomically distant from the suprasellar region. The
      effects of age at diagnosis, sex, L-T4 or GnRH agonist use, conventional vs.
      hyperfractionated RT, spinal RT, dose of spinal or cranial RT, chemotherapy, peak
      stimulated GH, dose and duration of GHRx, age at GHRx, time interval between RT
      and GHRx initiation, bone age, and height SDS at the start of GHRx were also
      assessed. Y1girls best correlated with younger age at diagnosis and im vs. sc
      GHRx. Y2girls best correlated with delayed bone age and younger age at diagnosis
      [Y1girls = -9.95 + 0.38 (age in years at diagnosis) + 3.11[GH method (1 = i.m.; 2
      = s.c.)]; r2 = 0.898; P = 0.02; Y2girls = -3.54 + 1.8 (bone age - age in years) +
      0.334 (age at diagnosis in years); r2= 0.956; P = 0.02]. Both Y1boys and Y2boys
      were strongly associated with spinal RT and younger age at diagnosis or treatment
      [Y1boys = -11.22 + 4.65 [spinal RT (1 = yes; 2 = no)] + 0.396 (age in years at
      diagnosis); r2= 0.64, P = 0.01; Y2boys = -6.32 + 0.23 (age in years at GH start)
      + 1.75 [spinal RT (1 = yes; 2 = no)]; r2= 0.646; P < 0.01]. This small historical
      cohort underscores that final stature is significantly reduced when immature
      bones are exposed to ionizing radiation. Intramuscular vs. sc use of GHRx is
      likely to be simply a surrogate marker for earlier methods of treatment. Of note,
      spinal RT did not significantly impact girls' final heights, whereas in boys,
      spinal RT strongly predicted ultimate short stature and a reduced response to
      GHRx. This sexually dichotomous response may be due in part to the greater
      percentage of spinal growth remaining for boys vs. girls throughout childhood.

PMID- 15579766
TI  - Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue
      and regulates growth and differentiation in thyroid cancer cells.
AB  - The Id (inhibitor of DNA binding) proteins are a family of helix-loop-helix (HLH)
      proteins (Id1, Id2, Id3, and Id4) that lack the basic domain necessary for DNA
      binding. The Id1 protein enhances cell proliferation and inhibits cellular
      differentiation in a variety of cell types. We have previously demonstrated that
      the Id1 gene is up-regulated in papillary and medullary thyroid cancers. In this
      study we characterized the expression and distribution of the Id1 protein in
      normal, hyperplastic, and neoplastic human thyroid tissue. We also evaluated the
      effect of the Id1 gene on thyroid cancer cell growth and markers of thyroid cell
      differentiation. We used semiquantitative immunohistochemistry to characterize
      Id1 protein expression in normal, hyperplastic (multinodular goiter and Graves'
      disease), and neoplastic thyroid tissue from 103 patients. Normal thyroid tissue
      had the lowest level of Id1 protein expression (P < 0.0001). Anaplastic thyroid
      cancer had the highest level (vs. benign and malignant thyroid tissues, P <
      0.01). Id1 protein expression was higher in malignant thyroid tissue than in
      hyperplastic thyroid tissue (P < 0.02). We found no significant association
      between the level of Id1 protein expression and patient age, sex, tumor-node
      metastasis stage, tumor size, primary tumor vs. lymph node metastasis, primary
      tumor vs. recurrent tumors, and extent of tumor differentiation. Inhibiting Id1
      mRNA expression in thyroid cancer cell lines using Id1 antisense oligonucleotides
      resulted in growth inhibition (P < 0.03) and decreased thyroglobulin and sodium
      iodine symporter mRNA expression (P < 0.02). In conclusion, Id1 is overexpressed
      in hyperplastic and neoplastic thyroid tissue and directly regulates the growth
      of thyroid cancer cells of follicular cell origin, but is not a marker of
      aggressive phenotype in differentiated thyroid cancer.

PMID- 15579767
TI  - Prostaglandin E2 mediates phosphorylation and down-regulation of the tuberous
      sclerosis-2 tumor suppressor (tuberin) in human endometrial adenocarcinoma cells
      via the Akt signaling pathway.
AB  - Prostaglandin (PG) E2 promotes tumor growth via interaction with its G protein
      coupled receptors and activation of intracellular signaling. Tuberous sclerosis 2
      (tuberin) is a tumor suppressor, which negatively regulates cell growth. Its
      phosphorylation results in its inactivation and targeted down- regulation, thus
      lifting the growth inhibition effects. This study investigated the expression and
      localization of tuberin in neoplastic and normal endometrium and the effect of
      PGE2 on phosphorylation of tuberin via the Akt pathway. Quantitative RT-PCR and
      Western blot analysis demonstrated reduced expression of tuberin in neoplastic
      tissue, compared with normal endometrial tissue. Tuberin expression was localized
      by immunohistochemistry to the glandular epithelial compartment in neoplastic and
      normal endometrium. We investigated the effect of PGE2 on phosphorylation of
      tuberin via the Akt pathway. Treatment of neoplastic and normal endometrium with
      100 nm PGE2 enhanced phosphorylated tuberin immunoreactivity in the glandular
      epithelium. PGE2 also phosphorylated Akt and tuberin in Ishikawa endometrial
      adenocarcinoma cells, leading to a reduction in expression of total tuberin
      protein. Cotreatment of cells with wortmannin or LY294002 inhibited the PGE2
      induced phosphorylation of Akt and tuberin. These data suggest that PGE2
      signaling may promote endometrial tumorigenesis by inactivation of tuberin after
      its phosphorylation via the Akt signaling pathway.

PMID- 15579768
TI  - Coexpression of fractalkine and its receptor in normal human endometrium and in
      endometrium from users of progestin-only contraception supports a role for
      fractalkine in leukocyte recruitment and endometrial remodeling.
AB  - Leukocytes are critical mediators of endometrial remodeling, but the mechanisms
      by which leukocyte subpopulations enter the uterus are currently unknown.
      Endometrial leukocytes have no genomic progesterone receptors; thus, we
      hypothesized that leukocyte migration is induced indirectly by progesterone
      regulated chemokines. Fractalkine (CX3CL1), a chemotactic membrane-bound adhesion
      factor, and its receptor (CX3CR1) were assessed by immunohistochemistry in
      endometrial samples across the menstrual cycle, in early pregnancy, and in women
      using progestin-only contraceptives. Fractalkine was localized predominantly to
      glandular epithelial and decidualized stromal cells, with the highest staining
      intensity in the secretory phase and early pregnancy. It was also detected in
      subpopulations of endometrial leukocytes (macrophages and uterine NK cells), with
      maximal numbers during the proliferative phase and early pregnancy. CX3CR1 was
      similarly colocalized to the glandular epithelium and decidualized stromal cells,
      with the highest expression in the secretory phase. CX3CR1-positive leukocytes
      (macrophages and neutrophils) were in greatest abundance during the menstrual
      phase. In the endometrium of women using progestin-only contraceptives,
      immunoreactive fractalkine was markedly reduced in the glandular epithelium, but
      was increased in decidualized stroma and infiltrating leukocytes. These findings
      support a number of roles for fractalkine in the endometrium, in the secretory
      phase, in early pregnancy, and when influenced by progestin-only contraceptives.

PMID- 15579769
TI  - Deregulation of estrogen receptor coactivator proline-, glutamic acid-, and
      leucine-rich protein-1/modulator of nongenomic activity of estrogen receptor in
      human endometrial tumors.
AB  - Proline-, glutamic acid-, and leucine-rich protein-1)PELP1/MNAR [modulator of
      nongenomic activity of estrogen receptor (ER)], a novel coregulatory protein,
      modulates genomic as well as nongenomic activity of ERs. We characterized the
      expression and localization of PELP1 in both benign and cancerous endometrium.
      Our results suggest that PELP1 is expressed in all stages of endometrium;
      however, this protein exhibits distinct localization depending on the phase.
      PELP1 is expressed in both the stroma and epithelial cells. Using the Ishikawa
      endometrial cancer model cell line and ER subtype-specific ligands, we found that
      PELP1 functionally interacts with both ERalpha and ERbeta and enhances their
      transcriptional responses. However, in endometrial cancer cells, endogenous PELP1
      is also required for optimal ligand-mediated transcription and proliferation
      responses. PELP1 promoted a tamoxifen-mediated agonistic action in endometrial,
      but not in breast cancer cells. PELP1 expression and localization are widely
      deregulated in endometrial cancers. In addition, PELP1 and ERbeta were localized
      predominantly in the cytoplasm of high-grade endometrial tumors. Our results
      suggest that PELP1 plays an essential role in the proliferation of cancerous
      endometrial cells.

PMID- 15579770
TI  - Thyrotropin (TSH)-induced production of vascular endothelial growth factor in
      thyroid cancer cells in vitro: evaluation of TSH signal transduction and of
      angiogenesis-stimulating growth factors.
AB  - Thyroid tumor growth requires angiogenesis, and vascular endothelial growth
      factor (VEGF) has been shown to be the most important endothelial mitogen. TSH is
      the major thyrotropic hormone, but its impact to modulate VEGF production has not
      yet been studied. Several other growth factors have also been shown to affect
      thyroid cancer cell growth and function in vitro. Therefore, the aim of the
      current study was to 1) establish the effect of TSH on VEGF as well as 2)
      evaluate the TSH signal transduction of this effect, and 3) screen other growth
      factors for the ability to modulate VEGF in thyroid cancer cell lines. HTC, a
      follicular cancer cell line lacking endogenous TSH receptor (TSHr), its receptor
      positive variant (HTC TSHr), and a cell line of Huerthle cell origin (XTC) were
      used. After stimulation with growth factors in vitro [TSH; epidermal growth
      factor (EGF), IGF, placenta growth factor, TGF-alpha, TGF-beta1, fibroblast
      growth factor, platelet-derived growth factor, and hepatocyte growth factor]
      cells were analyzed for VEGF gene expression by Northern blotting and for VEGF
      protein by enzyme immunoassay. TSHr signal transduction was evaluated by
      analyzing the effect of stimulators (cholera toxin, 8-bromo-cAMP, forskolin, and
      12-O-tetradecanoyl-phorbol-13-acetate) and inhibitors (2',5'-dideoxyadenosine and
      staurosporine) on VEGF protein levels under basal and TSH-stimulated conditions.
      TSH increased VEGF mRNA and protein in a dose-dependent manner in HTC TSHr and
      XTC cells by up to 40%. The effects of TSH were mediated by protein kinase C
      (PKC), rather than protein kinase A (PKA), stimulation, because inhibition of PKC
      by staurosporine resulted in a decrease in VEGF production of up to 65%, whereas
      inhibition of the PKA signal transduction pathway (2',5'-dideoxyadenosine)
      resulted in only a minor decrease. TSH was not the most powerful stimulator of
      VEGF production. TGF-beta1 and EGF were 1.5- to 2-fold more potent. Placenta
      growth factor and TGF-alpha did not induce VEGF production in TSHr-positive HTC
      cells, whereas they did induce VEGF production in TSHr-negative HTC cells. In
      thyroid cancer cell lines, TSH induces VEGF production involving the PKC, rather
      than the PKA, pathway. However, EGF and TGF-beta increase the capacity of thyroid
      cancer cells to provide VEGF more effectively than TSH. In the absence of a
      functioning TSHr, additional growth factors, such as TGF-alpha, increase capacity
      for VEGF stimulation.

PMID- 15579771
TI  - Microarray analysis of metastasis-associated gene expression profiling in a
      murine model of thyroid carcinoma pulmonary metastasis: identification of S100A4
      (Mts1) gene overexpression as a poor prognostic marker for thyroid carcinoma.
AB  - Tumor cell invasion and metastasis are the hallmark of malignant neoplasm.
      Despite advances in the management of thyroid carcinoma and other solid tumors,
      metastasis continues to be the most significant cause in cancer mortality. To
      gain new insights into this complex process in thyroid carcinoma, we established
      a thyroid carcinoma cell line (ARO-met2) with high metastatic capacity to the
      lung by sequential passage of a human anaplastic thyroid cancer cell line (ARO)
      through the lung of a nude mouse. Global patterns of gene expression were
      analyzed in cells of the parental ARO and the ARO-met2, using Atlas human cancer
      1.2 array with 1176 cancer-related genes. In total, 184 genes were differentially
      expressed more than 1.5 times, and 64 genes were differentially expressed over
      two times. Among those 64 genes, 43 were overexpressed, and 21 genes were
      underexpressed. Many genes whose increased expression was thought to be related
      to tumor progression were identified, such as c-Met, ezrin, integrin, motility
      related protein-1, cadherin, and S100A4. The most highly expressed gene is the
      S100A4 (8-fold higher than control), which is a member of a small calcium binding
      protein family and is involved in the cell proliferation and cancer progression.
      The S100A4 overexpression in the ARO-met2 cells was later confirmed by Northern
      blot and real-time reverse transcriptase-PCR. Analysis of 49 thyroid tumor
      specimens by real-time reverse transcriptase-PCR (eight benign goiters, 36
      papillary, and five anaplastic carcinomas) revealed that S100A4 overexpression
      was present in most advanced thyroid carcinomas and lymph node metastases, and
      was associated with poor prognosis. None of the benign goiters was found to have
      S100A4 overexpression. These data suggest that S100A4 could be used as a
      prognostic marker for thyroid carcinoma. Given that S100A4 is involved in tumor
      progression and metastasis, it may be a potential target for therapeutic
      intervention.

PMID- 15579772
TI  - Identification of chemokines important for leukocyte recruitment to the human
      endometrium at the times of embryo implantation and menstruation.
AB  - Human endometrium possesses a unique immunological environment enabling
      implantation of the semiallogeneic embryo. Large populations of macrophages and
      uterine-specific natural killer cells infiltrate the implantation site, believed
      to be important modulators of trophoblast invasion and decidualization. In the
      absence of pregnancy, there is a dramatic influx of neutrophils, eosinophils, and
      macrophages, likely to be critical for focal inflammatory endometrial
      destruction. However, little is known regarding selective recruitment of
      leukocyte subtypes. We employed a gene array approach to analyze the expression
      of 21 chemokines in endometrium. Real-time RT-PCR and immunohistochemistry was
      conducted to verify expression patterns and determine cellular source. Nine
      chemokines were highly abundant in human endometrium: monocyte chemotactic
      protein-3, eotaxin, fractalkine, macrophage inflammatory protein-1beta, 6Ckine,
      IL-8, hemofiltrate CC chemokine-1 and -4, and macrophage-derived chemokine.
      Chemokine mRNA was generally up-regulated during endometrial receptivity and
      early pregnancy, particularly of macrophage and natural killer chemoattractants.
      Chemokine protein was predominantly localized to epithelial glands, whereas
      differentiated stromal cells were a major source of chemokines after
      decidualization. This is the first study to use an unbiased approach to screen
      for endometrial chemokines, and we report the selective regulation of chemokines,
      corresponding to the recruitment of distinct leukocyte subpopulations required
      for pregnancy and menstruation.

PMID- 15579773
TI  - Forskolin, 8-Br-3',5'-cyclic adenosine 5'-monophosphate, and catalytic protein
      kinase A expression in the nucleus increase radioiodide uptake and sodium/iodide
      symporter protein levels in RET/PTC1-expressing cells.
AB  - RET/PTC1, a thyroid-specific oncogene, has been reported to down-regulate
      sodium/iodide symporter (NIS) expression and function in vitro and in vivo.
      Recently, RET/PTC1 has been shown to interfere with TSH signaling at multiple
      levels in thyroid cells. The objective of this study was to investigate whether
      RET/PTC1-mediated NIS reduction can be rescued by activating cAMP-protein kinase
      A (PKA) pathways. We showed that both forskolin and 8-Br-cAMP increase
      radioiodide uptake and NIS protein in RET/PTC1-expressing cells to the same
      extent as the parental PC Cl 3 cells. We found that RET/PTC1 decreases nuclear
      localization of catalytic PKA, and forskolin treatment was able to counteract
      this RET/PTC1 effect. Furthermore, transient expression of catalytic PKA in the
      nucleus increased radioiodide uptake and NIS protein in RET/PTC1-expressing
      cells. Taken together, these studies suggest that RET/PTC1 down-regulates NIS
      expression by interrupting TSH/cAMP signaling, and this RET/PTC1 effect can be
      reversed by activating cAMP-PKA pathways.

PMID- 15579774
TI  - A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor
      coactivator, exhibits decreased response to estrogen in vitro and associates with
      low bone mineral density in young Swedish women.
AB  - Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture,
      and the trait is under genetic control by a large number of genes. It is
      recognized that estrogen plays an important role in the maintenance of bone mass
      by binding to estrogen receptor alpha (ERalpha). RIZ1 has previously been shown
      to be a specific ERalpha coactivator and strongly enhances its function both in
      vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1
      P704 polymorphic variants (homozygous presence, P704+; absence, P704-;
      heterozygosity P704(+/-) of a proline at position 704) to coactivate the ERalpha
      and also examined the polymorphism associated to BMD of 343 Swedish women, aged
      20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response
      in coactivating ERalpha in a ligand- and dose-dependent manner compared with
      P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-),
      and 49% (P704(+/-)) and were in Hardy-Weinberg equilibrium. BMD at the heel was
      higher in the P704+ genotype group than in the P704(+/-) group (P = 0.02), which
      was evident also after corrections for fat and lean mass (P = 0.03). We conclude
      that RIZ1 may be a new candidate gene for involvement in the variation seen in
      BMD.

PMID- 15579775
TI  - Dynamic variability of hemostatic and fibrinolytic factors in young women.
AB  - This prospective study was designed to characterize the time course and
      variability of hemostatic and fibrinolytic risk factors over the course of a
      menstrual cycle in normal premenopausal women. Plasminogen activator inhibitor
      (PAI-1), tissue plasminogen activator, von Willebrand factor, fibrinogen, and
      fibrin D-dimer predict risk of coronary heart disease. Yet there is limited
      information describing the status of endogenous hormone concentrations and
      hemostatic and coagulation factors in premenopausal women. Twenty premenopausal
      women, mean age 34 +/- 7 yr, underwent testing over a cycle to measure endogenous
      hormones and hemostatic factors: estradiol and progesterone, FSH, LH; PAI-1,
      tissue plasminogen activator, von Willebrand factor, fibrin D-dimer, and
      fibrinogen as well as lipids: total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein-cholesterol, and triglycerides. There was
      cyclical variability in estradiol (P < 0.01) and progesterone (P < 0.001) during
      the follicular and luteal phases. Moreover, there was intra- and interindividual
      cyclical variation in hemostatic risk factors. Measures of PAI-1 (P < 0.01) and D
      dimer (P < 0.05) differed during the follicular and luteal phases. As estradiol
      concentration increased, PAI-I decreased. There was a significant correlation
      between total cholesterol and PAI-1 (r = 0.56, P < 0.05), low-density lipoprotein
      cholesterol and PAI-1 (r = 0.50, P < 0.05) as well as between total cholesterol
      and fibrinogen (r = 0.61, P < 0.05). There is significant cyclical variability in
      estradiol, FSH, and progesterone as well as the hemostatic factors, PAI-1 and
      fibrin D-dimer. Characterization of emerging hemostatic risk factors enhances
      understanding of normal physiology, provides insight into the relation between
      estrogen and hemostatic factors, and raises the potential for predicting coronary
      heart disease even in relatively young women.

PMID- 15579776
TI  - Divergent effect of endogenous and exogenous sex steroids on the insulin-like
      growth factor I response to growth hormone in short normal adolescents.
AB  - The lower responsiveness to GH in women than in men is probably due to a
      divergent effect of gonadal steroids. It is unknown, however, how the progressive
      increase in sex steroid production that occurs during puberty affects this
      responsiveness. To compare the effects of puberty and sex steroid administration
      on responsiveness to GH, we used the IGF-I generation test, in which the peak IGF
      I level 24 h after a single injection of GH (2 mg/m2) was studied in 117 healthy
      short subjects (56 females and 61 males). The subjects, aged 8-16 yr, were
      divided into four groups: prepuberty, early puberty, midpuberty, or pubertal
      delay. In the latter group, the IGF-I response was determined before and after
      priming with oral 17beta-estradiol in girls and im testosterone in boys. We also
      tested for an association between body composition (by dual energy x-ray
      absorptiometry) and the IGF-I response to GH. The IGF-I increment in response to
      GH (change in IGF-I from baseline) was correlated with the growth velocity sd
      score (P < 0.05). Progression throughout puberty was associated with an increase
      in both baseline IGF-I (P < 0.05) and the IGF-I increment in response to GH (P <
      0.05), with no gender difference. Pubertal category (pre-, early, and midpuberty;
      P < 0.05) and fat percentage (P < 0.05) were the main positive predictors of the
      IGF-I increment in response to GH, expressed as micrograms per liter as well as
      sd score, independently of baseline IGF-I. After sex steroid priming, both the GH
      peak in response to insulin-induced hypoglycemia and baseline IGF-I were
      increased (P < 0.05, after vs. before sex steroid). However, the IGF-I increment
      in response to GH decreased after oral 17beta-estradiol (P < 0.05), whereas it
      was unchanged after testosterone administration. Endogenous gonadal steroid
      secretion appears to result in increased responsiveness to GH in peripubertal
      girls and boys. By contrast, exogenous estrogen and testosterone, respectively,
      produce a relative decrease and no change in responsiveness to GH in similar
      populations, possibly through the achievement of sex steroid concentrations
      exceeding physiological ranges for age. Fat percentage was a positive determinant
      of the responsiveness to GH, suggesting a link between the energy stores and the
      anabolic action of GH.

PMID- 15579777
TI  - A low-carbohydrate/high-fat diet improves glucoregulation in type 2 diabetes
      mellitus by reducing postabsorptive glycogenolysis.
AB  - The aim of this study was to examine the mechanisms by which dietary carbohydrate
      and fat modulate fasting glycemia. We compared the effects of an eucaloric high
      carbohydrate (89% carbohydrate) and high-fat (89% fat) diet on fasting glucose
      metabolism and insulin sensitivity in seven obese patients with type 2 diabetes
      using stable isotopes and euglycemic hyperinsulinemic clamps. At basal insulin
      levels glucose concentrations were 148 +/- 11 and 123 +/- 11 mg/dl (8.2 +/- 0.6
      and 6.8 +/- 0.6 mmol/liter) on the high-carbohydrate and high-fat diet,
      respectively (P < 0.001), with insulin concentrations of 12 +/- 2 and 10 +/- 1
      microIU/ml (82 +/- 11 and 66 +/- 10 pmol/liter) (P = 0.08). Glucose production
      was higher on the high-carbohydrate diet (1.88 +/- 0.06 vs. 1.55 +/- 0.05
      mg/kg.min (10.44 +/- 0.33 vs. 8.61 +/- 0.28 micromol/kg.min) (P < 0.001) because
      of higher glycogenolysis. Gluconeogenic rates were not different between the
      diets. During the use of hyperinsulinemic euglycemic clamps, insulin-mediated
      suppression of glucose production and stimulation of glucose disposal were not
      different between the diets. Free fatty concentrations were suppressed by 89 and
      62% (P < 0.0001) on the high-carbohydrate and high-fat diet, respectively. We
      conclude that short-term variations in dietary carbohydrate to fat ratios affect
      basal glucose metabolism in people with type 2 diabetes merely through modulation
      of the rate of glycogenolysis, without affecting insulin sensitivity of glucose
      metabolism.

PMID- 15579778
TI  - Effect of short-term prednisone use on blood flow, muscle protein metabolism, and
      function.
AB  - Glucocorticoids can cause muscle atrophy, but the effect on muscle protein
      metabolism in humans has not been adequately studied to know whether protein
      synthesis, breakdown, or both are altered. We tested the effect of 6 d of oral
      prednisone (Pred, 0.5 mg/kg.d) on muscle protein metabolism and function. Six
      healthy subjects (three men/three women, 22-41 yr) completed two trials
      (randomized, double-blind, cross-over) with Pred and placebo. Fasting glucose,
      insulin, IGF-I, and glucagon were higher on Pred vs. placebo, whereas IGF-II and
      IGF binding protein-1 and -2 were lower. Whole-body amino acid fluxes, blood urea
      nitrogen, and urinary nitrogen loss were not statistically different between
      trials. Leg blood flow was 25% lower on Pred leading to 15-30% lower amino acid
      flux among the artery, vein, and muscle. However, amino acid net balance and
      rates of protein synthesis and breakdown were unchanged, as were synthesis rates
      of total mixed, mitochondrial, sarcoplasmic, and myosin heavy chain muscle
      proteins. Muscle mitochondrial function, muscle strength, and resting energy
      expenditure were also unchanged. These results demonstrate that a short-term
      moderate dose of prednisone affects glucose metabolism but has no effect on whole
      body or leg muscle protein metabolism or muscle function.

PMID- 15579779
TI  - X-chromosome inactivation patterns and androgen receptor functionality influence
      phenotype and social characteristics as well as pharmacogenetics of testosterone
      therapy in Klinefelter patients.
AB  - Klinefelter syndrome is characterized by a vast range of phenotypes related to
      androgen effects. Testosterone (T) acts via the X-linked androgen receptor gene
      carrying the CAG repeat (CAGn) polymorphism, the length of which is inversely
      associated with androgen action and might account for the marked variation in
      phenotypes. In 77 newly diagnosed and untreated Klinefelter patients with a
      47,XXY karyotype we assessed phenotype and social traits in relation to X
      weighted biallelic CAGn length using X-chromosome inactivation analysis after
      digestion of leukocyte DNA with methylation-sensitive HpaII. Forty-eight men were
      hypogonadal and received T substitution therapy; in these, pharmacogenetic
      effects were investigated. The shorter CAGn allele was preferentially inactive.
      CAGn length was positively associated with body height. Bone density and the
      relation of arm span to body height were inversely related to CAGn length. The
      presence of long CAGn was predictive for gynecomastia and smaller testes, whereas
      short CAGn were associated with a stable partnership and professions requiring
      higher standards of education also when corrected for family background. There
      was a trend for men with longer CAGn to be diagnosed earlier in life. Under T
      substitution, men with shorter CAGn exhibited a more profound suppression of LH
      levels, augmented prostate growth, and higher hemoglobin concentrations. A
      significant genotype-phenotype association exists in Klinefelter patients:
      androgen effects on appearance and social characteristics are modulated by the
      androgen receptor CAGn polymorphism. The effects of T substitution are
      pharmacogenetically modified. This finding is magnified by preferential
      inactivation of the more functional short CAGn allele.

PMID- 15579780
TI  - Insulin resistance and impaired insulin secretion in prenatally androgenized male
      rhesus monkeys.
AB  - Polycystic ovary syndrome (PCOS) is a familial disease. Affected males harbor
      some of the metabolic deficits seen in affected females. The prenatally
      androgenized (PA) female rhesus monkey, an animal model for PCOS, manifests
      glucoregulatory and reproductive abnormalities similar to those seen in PCOS
      women. The purpose of this study was to determine whether exposure of fetal male
      rhesus monkeys to testosterone excess would induce glucoregulatory and
      reproductive deficits. Seven adult PA males and seven matched controls underwent
      somatometric measurements, sex steroid analysis, and a frequently sampled i.v.
      glucose tolerance test. Body measurements were similar in the two groups,
      although arm circumference was greater in control compared with PA males (P <
      0.01). There were no differences in neonatal weight or serum levels of sex
      steroids between the two male groups. Measures of insulin sensitivity and
      pancreatic beta-cell compensation (disposition index) were clearly diminished in
      PA compared with control males [insulin sensitivity: PA, mean 0.8 (95% confidence
      interval, 0.11, 5.82); controls, 3.06 (1.51, 6.19) x 10(-4)/min/microU/ml; P <
      0.05; disposition index: PA, 226.38 (69.54, 383.22); controls, 509.21/min
      (306.52, 711.89); P < 0.02]. PA males do not exhibit elevated androgens during
      adulthood, suggesting that insulin resistance and impaired pancreatic beta-cell
      function may result from fetal reprogramming of key metabolic tissues.

PMID- 15579781
TI  - Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for
      additional locus heterogeneity.
AB  - Hyperinsulinism of infancy is a genetically heterogeneous disease characterized
      by dysregulation of insulin secretion resulting in severe hypoglycemia. To date,
      mutations in five different genes, the sulfonylurea receptor (SUR1, ABCC8), the
      inward rectifying potassium channel (K(IR)6.2, KCNJ11), glucokinase (GCK),
      glutamate dehydrogenase (GLUD1), and short-chain 3-hydroxyacyl-coenzyme A
      dehydrogenase (SCHAD), have been implicated. Previous reports suggest that, in
      40% of patients, no mutation can be identified in any of these genes, suggesting
      additional locus heterogeneity. However, previous studies did not screen all five
      genes using direct sequencing, the most sensitive technique available for
      mutation detection. We selected 15 hyperinsulinism of infancy patients and
      systematically sequenced the promoter and all coding exons and intron/exon
      boundaries of ABCC8 and KCNJ11. If no mutation was identified, the coding
      sequence and intron/exon boundaries of GCK, GLUD1, and SCHAD were sequenced.
      Seven novel mutations were found in the ABCC8 coding region, one mutation was
      found in the KCNJ11 coding region, and one novel mutation was found in each of
      the two promoter regions screened. Functional studies on beta-cells from six
      patients showed abnormal ATP-sensitive K+ channel function in five of the
      patients; the sixth had normal channel activity, and no mutations were found.
      Photolabeling studies using a reconstituted system showed that all missense
      mutations altered intracellular trafficking. Each of the promoter mutations
      decreased expression of a reporter gene by about 60% in a heterologous expression
      system. In four patients (27%), no mutations were identified. Thus, further
      genetic heterogeneity is suggested in this disorder. These patients represent a
      cohort that can be used for searching for mutations in other candidate genes.

PMID- 15579782
TI  - Urinary excretion of steroid metabolites after chronic androstenedione ingestion.
AB  - Urinary steroid excretion after androstenedione intake has been examined after a
      single dose of 50 mg and single doses of 100 or 300 mg/d for 7 d. We evaluated
      the effects of 28 d of 100 mg three times a day (t.i.d.) androstenedione intake
      on urinary steroid excretion. Twenty healthy men, ages 30-39 yr (33.5 +/- 0.6),
      consumed 100 mg androstenedione t.i.d. or placebo for 28 d. Urine samples were
      analyzed for testosterone, epitestosterone, androsterone, and etiocholanolone via
      HPLC/tandem mass spectrometry on d 0 and 28. Androstenedione intake increased (P
      < 0.05) urinary testosterone 35.1 +/- 10.5 ng/ml vs. 251.6 +/- 87.5 ng/ml,
      epitestosterone 35.3 +/- 8.8 ng/ml vs. 99.7 +/- 28.7 ng/ml, androsterone 2,102 +/
      383 ng/ml vs. 15,767 +/- 3,358 ng/ml, and etiocholanolone 1,698 +/- 409 ng/ml
      vs. 11,329 +/- 2,656 ng/ml (means +/- se). Although the testosterone to
      epitestosterone ratio (T/E) tended to increase with androstenedione intake (1.2
      +/- 0.3 vs. 4.0 +/- 1.6; P = 0.12), only one subject had a urinary T/E greater
      than the current Olympic criteria (>6.0) for a positive drug test. Chronic intake
      of 100 mg androstenedione t.i.d. increases the urinary excretion of steroid
      metabolites. Due to inconsistent increases in the T/E ratio, the T/E ratio may
      not effectively detect androstenedione use.

PMID- 15579783
TI  - Preeclampsia and future cardiovascular disease: potential role of altered
      angiogenesis and insulin resistance.
AB  - Altered angiogenesis and insulin resistance are associated with preeclampsia and
      cardiovascular disease (CVD), and women with preeclampsia appear to be at
      increased risk of future CVD. We hypothesized that these factors are detectable
      in asymptomatic postpartum women with a history of preeclampsia and may represent
      pathophysiological mechanisms bridging preeclampsia and future CVD. We measured
      fasting insulin, glucose, vascular endothelial growth factor, and its circulating
      inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women
      with a history of preeclampsia and 32 women with prior normotensive pregnancies
      at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance
      (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per
      liter])/22.5] was calculated. Compared with women with normal pregnancies, women
      with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/-
      6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04).
      Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with
      prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01),
      and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a
      history of preeclampsia. Women with a history of preeclampsia demonstrate altered
      expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr
      postpartum. These factors may contribute to their risk of future CVD.

PMID- 15579784
TI  - The heritability of hypothalamus pituitary adrenal axis responses to psychosocial
      stress is context dependent.
AB  - Individual differences in the response of the hypothalamus pituitary adrenal axis
      to stress are known to play an important role in health and disease risk. The
      origins, or determinants, of these individual differences are not well
      understood. To date, no study has examined the effects of context on the
      heritability of psychoendocrine stress responses. In the present study, 58 male
      twin pairs were exposed to a psychosocial stressor (Trier Social Stress Test)
      three times at weekly intervals, and their salivary and total cortisol, ACTH, and
      heart rate responses were assessed. Modest heritabilities were observed for all
      measures at the first stress exposure (all h2 < 0.33), but heritability estimates
      increased substantially with repetition of the stressor (T3: all h2 > 0.97).
      Concurrently, only the first but not the second and third Trier Social Stress
      Test exposure induced a significant increase in state anxiety (T1: P < 0.01, T2
      and T3: n.s.), suggesting low heritabilities in a new, anxiety-evoking context
      and high heritabilities in a familiar, low-anxiety context. These findings
      challenge previous reports on a low heritability of markers of stimulated
      hypothalamus pituitary adrenal axis activity and are the first to document the
      relevance of context for psychoendocrine heritability estimates.

PMID- 15579785
TI  - Plasma catecholamines and the counterregulatory responses to hypoglycemia in
      infants: a critical role for epinephrine and cortisol.
AB  - The purpose of this study was to define plasma catecholamine responses as part of
      the counterregulatory hormonal reaction to hypoglycemia in infants after a
      regular 3- to 4-h feed was omitted. Hormone levels were assessed once, at the end
      of the fast or at hypoglycemia. The 121 infants were subdivided into three groups
      for analysis: normoglycemia (n = 94, 78%); transient hypoglycemia (n = 11, 9%);
      or severe and persistent hypoglycemia (n = 16, 13%). The severe and persistent
      hypoglycemic group had significantly higher levels of cortisol and epinephrine
      than the normoglycemic group. Norepinephrine and glucagon levels did not differ
      between the groups. Human GH levels were higher in the transiently hypoglycemic
      group but not in the severe and persistent hypoglycemic group. Prefeed blood
      lactate levels differed significantly among the groups and were highest in the
      severe and persistent groups. Multiple regression analysis showed that cortisol
      levels were significantly higher in infants who had severe and persistent
      hypoglycemia. The counterregulatory hormonal response in infants to severe and
      persistent hypoglycemia was limited to elevations in only cortisol and
      epinephrine levels but did not involve glucagon or human GH. This limited
      hormonal response may also contribute to the frequent occurrence of hypoglycemia
      in these infants.

PMID- 15579786
TI  - Association of the cytotoxic T lymphocyte-associated antigen 4 gene with type 1
      diabetes: evidence for independent effects of two polymorphisms on the same
      haplotype block.
AB  - A recent study mapped the known association of type 1 diabetes with the cytotoxic
      T lymphocyte-associated antigen 4 gene to a polymorphism at the 3'end (+6230G>A),
      but could not rule out additional contribution from the 5' end of the gene. To
      examine this possibility, we analyzed four polymorphisms at the 5'-flanking
      region for effects independent of +6230G>A. We confirm, by the transmission
      disequilibrium test, in 496 family trios overtransmission of the susceptibility
      allele (G) at +6230 (217/168; P = 0.013). Of the four promoter polymorphisms, one
      (-319C>T) showed overtransmission of the C allele (97/58; P = 0.0017). Because
      the undertransmitted T at the promoter is in linkage disequilibrium with the
      overtransmitted G at +6230G>A, the effect observed at the promoter cannot be
      accounted for by linkage disequilibrium with the +6230G>A. We confirm this by
      showing that parents heterozygous at the promoter but homozygous at +6230
      overtransmit the C promoter allele even more significantly (53/24; P = 9 x 10(
      4)). In vitro, the T promoter allele directs higher luciferase expression in
      Jurkat cells by 42% (P = 0.006), a difference also found in lymphocyte mRNA from
      eight individuals heterozygous at the promoter, but homozygous at +6230 (P = 1.3
      x 10(-4)). Thus, the +6230G>A cannot be the sole functional variant. Either the
      two polymorphisms define a haplotype carrying the (yet unexamined) functional
      variant or the -319C>T contributes to the genetic association independently, a
      possibility suggested by the functional evidence we present.

PMID- 15579787
TI  - Gender differences of regional abdominal fat distribution and their relationships
      with insulin sensitivity in healthy and glucose-intolerant Thais.
AB  - To determine gender differences of regional abdominal fat distribution and their
      relationships with insulin sensitivity in healthy and glucose-intolerant Thais,
      44 subjects, 22 men and 22 body mass index-matched women, with normal and
      abnormal glucose tolerance, which included subjects with impaired glucose
      tolerance and diabetes, were studied. Total body fat and total abdominal fat
      (TAF) at L1-L4 were measured by dual-energy x-ray absorptiometry. Regional
      abdominal fat, which consists of sc abdominal fat and visceral abdominal fat, was
      determined by single-slice computerized tomography of the abdomen at L4-L5 disc
      space level. Insulin sensitivity was determined by euglycemic hyperinsulinemic
      clamp and expressed as glucose infusion rate (GIR). With comparable body mass
      index, visceral abdominal fat was most strongly correlated with GIR after
      adjustment with percent total body fat in both healthy (r = -0.8155; P = 0.007)
      and glucose-intolerant women (r = -0.7597; P = 0.011), whereas TAF was most
      strongly correlated with GIR in both healthy (r = -0.8114; P = 0.008) and glucose
      intolerant men (r = -0.6194; P = 0.101). By linear regression analysis, visceral
      abdominal fat accounted for 35.0% (beta = -3.53 x 10(-2); P = 0.001) of GIR
      variance in women, whereas TAF accounted for 39.3% (beta = -1.28 x 10(-4); P <
      0.0001) of GIR variance in men. We conclude that there are gender differences in
      the relationships of regional abdominal fat and insulin sensitivity in slightly
      obese healthy and glucose-intolerant Thais, the difference of which may possibly
      be in part due to the difference of abdominal fat patterning between genders.

PMID- 15579788
TI  - Triiodothyronine addition to paroxetine in the treatment of major depressive
      disorder.
AB  - There is evidence that thyroid hormone T3 increases serotonergic
      neurotransmission. Therefore, T3 addition to antidepressants may improve
      treatment response in major depression. In nonrefractory depression, T3 addition
      to tricyclic antidepressants indeed accelerates treatment response. Current
      therapeutic practice favors selective serotonin reuptake inhibitors. This is the
      first study to investigate the efficacy of T3 addition to paroxetine in major
      depression. One hundred thirteen patients with major depressive disorder were
      randomly assigned to 8 wk of double-blind outpatient treatment with low-dose T3
      (25 microg), high-dose T3 (25 microg twice daily), or placebo in addition to
      paroxetine 30 mg daily. A total of 106 patients started treatment and were
      included in the outcome analysis. Response rate after 8 wk (reduction of Hamilton
      Rating Scale for Depression score > or = 50%) was 46% in all three treatment arms
      (P = 0.99). T3 addition did not accelerate clinical response to paroxetine, nor
      was an effect of T3 found when only women were analyzed. Patients on T3 addition
      reported more adverse events than patients on placebo comedication. In
      conclusion, these results do not support a role for T3 addition to selective
      serotonin reuptake inhibitors in the treatment of nonrefractory major depressive
      disorder. On the contrary, more adverse reactions occurred in T3-treated
      patients.

PMID- 15579789
TI  - Weight loss reduces circulating asymmetrical dimethylarginine concentrations in
      morbidly obese women.
AB  - The endogenous nitric oxide-synthase inhibitor asymmetrical dimethyl-L-arginine
      (ADMA) is elevated in patients with increased risk for arteriosclerosis. Obesity
      is a risk factor for cardiovascular disease. We measured plasma ADMA
      concentrations in morbidly obese women before and after weight loss following
      gastroplastic surgery. ADMA and symmetrical dimethyl-L-arginine concentrations
      were analyzed by HPLC from 34 female patients (age 41 +/- 7 yr) with a body mass
      index (BMI) of 49 +/- 1 kg/m2 before and 14 months after vertical ring
      gastroplasty. Age-matched healthy women (BMI < 25 kg/m2; n = 24) were studied as
      controls. After gastroplastic surgery, BMI decreased to 34 +/- 1 kg/m2 in obese
      women (P < 0.00001), and ADMA concentrations were reduced from 1.06 +/- 0.06
      micromol/liter at baseline to 0.81 +/- 0.04 micromol/liter after weight loss (P <
      0.00001). Symmetrical dimethyl-L-arginine plasma levels were not affected. ADMA
      correlated with high-sensitivity C-reactive protein at baseline (r = 0.42; P <
      0.05) and after weight loss (r = 0.56; P < 0.005). No association with blood
      pressure or plasma lipids could be observed. ADMA concentrations were lower in
      controls (0.68 +/- 0.04 micromol/liter; P < 0.05) compared with obese patients
      before or after weight reduction. The decrease of highly elevated ADMA
      concentrations in morbidly obese patients is paralleled by improvement of
      parameters associated with the metabolic syndrome after weight loss.

PMID- 15579790
TI  - An analysis of the genetic factors involved in testicular descent in a cohort of
      14 male patients with anorchia.
AB  - Anorchia, or the "vanishing testis syndrome," is characterized by the absence of
      testis in a 46,XY individual with a male phenotype. The etiology is unknown;
      however, the familial occurrence of the disease and the association of this
      phenotype with 46,XY gonadal dysgenesis has led to the suggestion that genetic
      factors, which play a role in testicular determination, may be involved.
      Alternatively, exploratory laparoscopy has suggested that anorchia may be caused
      by a prenatal testicular vascular accident associated with torsion during
      testicular descent. We screened a cohort of 14 boys with bilateral anorchia for
      mutations in the Y chromosome-linked testis-determining gene SRY (sex-determining
      region, Y chromosome); in the gene necessary for correct testicular descent,
      INSL3; and in the gene of its receptor (LGR8). Mutations in the INSL3 gene and
      the LGR8 T222P mutation are known to cause cryptorchidism. We confirmed previous
      reports that mutations in the SRY gene are not associated with anorchia. Although
      a common polymorphism was identified in the INSL3 gene, no mutations were
      observed. The recurrent T222P mutation in the LGR8 gene was not found in any of
      the patients. These data show for the first time a lack of association between
      genetic factors necessary for correct testicular descent and anorchia.

PMID- 15579791
TI  - Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the
      conversion from impaired glucose tolerance to type 2 diabetes. The Finnish
      Diabetes Prevention Study.
AB  - Type 2 diabetes is caused by defective insulin secretion and impaired insulin
      action. We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes
      are associated with increased risk of type 2 diabetes in 490 subjects with
      impaired glucose tolerance participating in the Finnish Diabetes Prevention
      Study. The 1273AGA allele of the SUR1 gene was associated with a 2-fold risk of
      type 2 diabetes [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.19-3.36;
      P = 0.009]. This silent polymorphism was in linkage disequilibrium with three
      promoter polymorphisms (G-2886A, G-1561A, and A-1273G), and they formed a high
      risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09
      3.27; P = 0.023). Subjects with both the high-risk haplotype of the SUR1 gene and
      the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to
      diabetes compared with those without any of these risk genotypes (OR, 5.68; 95%
      CI, 1.75-18.32; P = 0.004). We conclude that the polymorphisms of the SUR1 gene
      predicted the conversion from impaired glucose tolerance to type 2 diabetes and
      that the effect of these polymorphisms on diabetes risk was additive with the
      E23K polymorphism of the Kir6.2 gene.

PMID- 15579792
TI  - Contributions of gender and systemic estradiol and testosterone concentrations to
      maximal secretagogue drive of burst-like growth hormone secretion in healthy
      middle-aged and older adults.
AB  - To test whether concentrations of estradiol and testosterone predict GH responses
      to mechanistically distinct secretagogues in healthy older adults, we studied 16
      volunteers (n = 10 men, n = 6 women, age 49-72 yr) in each of six randomly
      ordered sessions as follows: 1) saline; 2) l-arginine; 3) aerobic exercise; 4)
      GHRH; 5) GH-releasing peptide (GHRP)-2; and 6) somatostatin-induced rebound.
      Statistical comparisons disclosed that stimulus type (P < 0.001) and the
      interaction between gender and stimulus type (P = 0.023) determine GH secretion.
      In women, each secretagogue, except exercise and somatostatin-induced rebound,
      stimulated GH secretion by 2.6- to 6.4-fold over saline/rest (P < 0.023). In men,
      somatostatin-induced rebound drove GH secretion by 4.6-fold (P = 0.004), exercise
      by 16-fold (P < 0.001), and other secretagogues by 18- to 109-fold over
      saline/rest (each P < 0.001). Gender comparisons disclosed greater GH secretion
      in men than women after somatostatin-induced rebound (P = 0.008) and GHRP-2
      injection (P < 0.001) and conversely greater GH secretion in women than men after
      saline (P = 0.013). Regression analysis showed that individual concentrations of
      estradiol (r = 0.80, P = 0.002) and testosterone (r = 0.63, P = 0.008) and their
      combination (r = 0.86, P < 0.001) strongly predict responses to GHRP-2 only. We
      conclude that among healthy middle-aged and older adults, the action of GHRP is
      uniquely determined by gender and physiological concentrations of testosterone
      and estradiol.

PMID- 15579793
TI  - Pharmacodynamics of a single low dose of long-acting recombinant follicle
      stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women
      with World Health Organization group II anovulatory infertility.
AB  - In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects
      received a single s.c. injection of placebo (n = 10) or recombinant long-acting
      FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV
      Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or
      60 microg (n = 11). The injection was given 2 or 3 d after the onset of a
      spontaneous or progestagen-induced withdrawal bleed. After drug administration,
      the induced follicular response varied widely among subjects in each dose group.
      The percentage of subjects with a follicular response (at least one follicle > or
      = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in
      the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In
      responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4,
      and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a
      single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose
      response for the number of follicles was statistically significant within the
      dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly
      correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak
      concentrations of inhibin-B and E2 correlated with the number of follicles
      observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall
      per treatment group, serum E2 and inhibin B concentrations significantly
      increased only in the two highest FSH-CTP dose groups, reaching peak
      concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group.
      Thereafter these hormone values declined rapidly, returning to baseline within 1
      wk after FSH-CTP administration. In total, nine of the 55 treated subjects
      (16.4%) ovulated after drug administration: one subject in the placebo group, two
      subjects in the 7.5-microg group, three subjects in the 15-microg group, two in
      the 30-microg group, and one in the 60-microg group. Three subjects had
      monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH
      CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple)
      ovulation was prevented by GnRH antagonist administration. Thus, a single low
      dose of long-acting FSH-CTP was able to induce one or more follicles to grow up
      to ovulatory sizes, but the anovulatory status was not reversed because the
      incidence of subsequent (mono)ovulations was low.

PMID- 15579794
TI  - Residual beta-cell function more than glycemic control determines abnormalities
      of the insulin-like growth factor system in type 1 diabetes.
AB  - The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to
      investigate whether abnormalities are found in patients in very good glycemic
      control and, if so, to estimate the role of residual beta-cell function. Patients
      with hemoglobin A1c (HbA1c) less than 6% (reference range, 3.6-5.4%) were
      selected for the study. Twenty-two men and 24 women, aged 41.3 +/- 13.8 yr (mean
      +/- SD), with a diabetes duration of 17.8 +/- 14.6 yr participated. Healthy
      controls (15 women and nine men), aged 41.3 +/- 13.0 yr, were also studied.
      Overnight fasting serum samples were analyzed for HbA1c, C peptide, free and
      total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3
      proteolysis. HbA1c was 5.6 +/- 0.5% in patients and 4.4 +/- 0.3% in controls.
      Total IGF-I was 148 +/- 7 microg/liter in patients and 178 +/- 9 microg/liter in
      controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein
      were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated
      compared with control values. Patients with detectable C peptide (> or =100
      pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and
      lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide
      level despite having identical average HbA1c. IGFBP-3 proteolysis did not differ
      between patients and controls. Despite very good glycemic control, patients with
      type 1 diabetes and no endogenous insulin production have low free and total IGF
      I. Residual beta-cell function, therefore, seems more important for the
      disturbances in the IGF system than good metabolic control per se, suggesting
      that portal insulin delivery is needed to normalize the IGF system.

PMID- 15579795
TI  - Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation
      syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism.
AB  - The ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening
      complication of ovarian stimulation treatments for in vitro fertilization
      (i.v.f.). Recently, three different mutations of the FSH receptor (FSHr) have
      been identified in patients who presented recurrent spontaneous OHSS. This
      prompted us to study a possible association between coding polymorphisms of the
      FSHr and the occurrence of iatrogenic OHSS. We sequenced the region of the FSHr
      gene encompassing the A307T and S680N polymorphisms of exon 10 of FSHr in 37
      Caucasian females who developed OHSS after an IVF cycle in our fertility clinic,
      130 Caucasian female patients who were treated by i.v.f. but never developed
      OHSS, and 99 Caucasian female controls. The FSHr allele frequencies in the
      Caucasian control population were identical to what has already been published
      (39% S680 61% N680). The control i.v.f. population was enriched in the S680
      allele compared with the Caucasian control population (51% S680; 49% N680; P =
      0.016). The OHSS population had a even higher enrichment in the S680 allele
      compared with the Caucasian control population (57% S680; 43% N680; P = 0.010).
      These results were unexpected, because the frequency of the S680 allele was
      previously found to be increased among poor responders to FSH stimulation. In a
      second phase, we studied FSHr allele frequencies according to the severity of
      OHSS. Interestingly, a significant enrichment in the allele N680 was observed as
      the severity of OHSS increased (P = 0.034). Bearing in mind the limitations of
      the small number of patients studied and the possibility of sampling biases,
      these results suggest that the genotype in position 680 of the FSHr cannot
      predict which patients will develop OHSS, but could be a predictor of severity of
      symptoms among OHSS patients.

PMID- 15579796
TI  - Biallelic expression of the Gsalpha gene in human bone and adipose tissue.
AB  - Mutations of the Gsalpha gene inherited from the mother lead to
      pseudohypoparathyroidism (PHP) type Ia (PHP Ia), in which Albright's hereditary
      osteodistrophy is associated to resistance to the action of different hormones,
      whereas the same mutations inherited from the father lead to isolated Albright's
      hereditary osteodistrophy [pseudo-PHP (PPHP)]. Accordingly, it has been suggested
      that Gsalpha is under tissue-specific imprinting control, and recent studies
      provided evidence for a predominant maternal origin of Gsalpha transcripts in
      different endocrine organs involved in the PHP Ia phenotype. To establish whether
      Gsalpha is imprinted also in tissues that are site of alteration both in PHP Ia
      and PPHP, we selected 20 bone and 10 adipose tissue samples, which were
      heterozygous for a known polymorphism in exon 5. Expression from both parental
      alleles was evaluated by RT-PCR and enzymatic digestion of the resulting
      fragments. By this approach, the great majority of the samples analyzed showed an
      equal expression of the two alleles. Our results provide evidence for the absence
      of Gsalpha imprinting in human bone and fat and suggest that the clinical finding
      of osteodystrophy and obesity in PHP Ia and PPHP patients despite the presence of
      a normal Gsalpha allele is likely due to Gsalpha haploinsufficiency in these
      tissues.

PMID- 15579797
TI  - Altered thyroid and adrenal function in children born at term and preterm, small
      for gestational age.
AB  - Intrauterine growth retardation may permanently influence the endocrine system by
      affecting its programming during development. The aim of this study was to
      evaluate thyroid and adrenal function together with insulin sensitivity in a
      group of children born small for gestational age (SGA). Forty SGA children (mean
      age, 6.7 +/- 1.7 yr) and 35 children born appropriate for gestational age (mean
      age, 6.5 +/- 2.2 yr) were selected for the study. TSH, free T4, free T3 (fT3),
      rT3, antithyroid antibodies, cortisol, and dehydroepiandrosterone sulfate (DHEAS)
      were assessed. Insulin sensitivity was evaluated with the quantitative insulin
      sensitivity check index (QUICKI). A thyroid ultrasound was also performed in the
      SGA children. We found that TSH was significantly higher in SGA than in children
      born appropriate for gestational age [2.9 +/- 1.1 vs. 1.7 +/- 0.7 microU/ml
      (mIU/liter); P < 0.001]; furthermore, eight SGA children (20%), seven born
      preterm and one at term, had TSH levels above the upper limit of normality. fT3
      was also higher in SGA children (4.2 +/- 0.4 vs. 3.6 +/- 0.6 pg/ml; 6.4 +/- 0.6
      vs. 5.5 +/- 0.9 pmol/liter; P < 0.0001), whereas no difference was found for free
      T4, rT3, and the fT3/rT3 ratio. Urinary iodine was normal, and antithyroid
      antibodies were absent. Thyroid ultrasound showed a normal echographic pattern
      with a normal volume in SGA children. Serum cortisol was similar in both groups,
      whereas DHEAS was significantly lower in SGA subjects (43 +/- 18 vs. 65 +/- 50
      microg/dl; 1.1 +/- 0.4 vs. 1.7 +/- 1.3 micromol/liter; P < 0.05). There was no
      difference in insulin sensitivity between the two groups. Birth length and birth
      weight were the main determinants of TSH and DHEAS serum levels, respectively. In
      conclusion, functional thyroid and adrenal changes have been found in children
      who suffered from intrauterine growth retardation. A larger survey with an
      appropriate follow-up is, however, required to confirm these findings and to
      assess their natural evolution.

PMID- 15579798
TI  - Sustained growth hormone (GH) and insulin-like growth factor I responses to
      prolonged high-dose twice-daily GH-releasing hormone stimulation in middle-aged
      and older men.
AB  - Postulated mechanisms underlying the relative hyposomato-tropism of aging include
      reduced hypothalamic drive by GHRH. To test this notion, we administered 1 mg (n
      = 11) vs. 4 mg (n = 11) recombinant human GHRH-1,44-amide s.c. twice daily for 3
      months in a double-blind, parallel-cohort design to 22 healthy men (ages, 53-68
      yr). After 3 months, GHRH elevated: overnight GH concentrations from 0.71 +/-
      0.19 to 1.74 +/- 0.39 microg/liter (P < 0.001; 1 mg) and from 0.80 +/- 0.15 to
      5.12 +/- 0.40 microg/liter (P < 0.001; 4 mg) and IGF-I concentrations from 117 +/
      14 to 234 +/- 20 microg/liter (P = 0.007; 1 mg) and from 147 +/- 13 to 286 +/-
      22 microg/liter (P < 0.001; 4 mg). Only the higher GHRH dose also increased total
      body water (tritium space; P = 0.024) and fat-free mass (dual-energy x-ray
      absorptiometry; P = 0.021), and reduced total abdominal adiposity (computed axial
      tomography scan; P = 0.042). Both supplementation schedules shortened the time
      required to walk 30 m and ascend four flights of stairs (P < 0.025 each). Lower
      extremity strength, aerobic capacity, and bone mineral density did not change.
      Local injection site reactions were common. We conclude that sc administration of
      a large dose of GHRH (4 mg) twice daily for 3 months elevates GH and IGF-I
      concentrations, increases total body water and fat-free mass, reduces total
      abdominal adiposity, and enhances certain performance measures in healthy aging
      men but causes local skin reactions.

PMID- 15579799
TI  - Improved glycemic control in subjects with atypical diabetes results from
      restored insulin secretion, but not improved insulin sensitivity.
AB  - African-American subjects often present with hyperglycemic crisis (diabetic
      ketoacidosis or severe hyperglycemia), yet subsequently are treated without
      insulin. The pathophysiology of this unique condition is unknown. We hypothesized
      that recovery from atypical diabetes with intensive insulin therapy resulted from
      a reversal of a defect in beta-cell function and improved insulin sensitivity. We
      studied eight newly diagnosed, antibody-negative African-American subjects (age,
      34-56 yr) who presented with hyperglycemic crisis. Subjects were studied at
      baseline after overnight glycemic control and again after 3 wk and 3 months of
      intensive insulin therapy. Insulin sensitivity (SI) was determined from an
      insulin-modified, frequently sampled i.v. glucose tolerance test, and insulin
      secretion was measured as the acute insulin response to glucose and to a glucagon
      stimulation test. Fructosamine and hemoglobin A1c declined significantly with
      intensive insulin therapy, and insulin requirements decreased over time. Both
      acute insulin response to glucose and the C peptide response to glucagon
      stimulation test improved by 3 wk (P = 0.02 vs. baseline), and improvements were
      maintained at 3 months (P = 0.02 vs. baseline). In contrast, the SI remained low
      throughout the study. We demonstrate that improved glycemic control correlates
      with a remarkable recovery of beta-cell function, but no change in SI.

PMID- 15579800
TI  - Common allelic variants of exons 10, 12, and 33 of the thyroglobulin gene are not
      associated with autoimmune thyroid disease in the United Kingdom.
AB  - Thyroglobulin (Tg) is a major autoantigen for autoimmune thyroid disease (AITD).
      The Tg gene (Tg) has been mapped to chromosome 8q24, which has recently been
      linked in two independent studies to AITD. Association of specific alleles of
      microsatellite markers within Tg itself supports a role for Tg as a good
      candidate susceptibility locus for AITD. Resequencing of the Tg exons has led to
      the identification of a number of novel single nucleotide polymorphisms, four of
      which have been reported to be associated with AITD. Resequencing of Tg in
      Caucasian subjects in the United Kingdom (UK) has confirmed the presence of four
      single nucleotide polymorphisms in exons 10, 12, and 33. However, in the largest
      case-control association study to date with adequate power to detect the reported
      effect if present, we found no evidence for association of the Tg DNA variants
      with AITD in the UK. These data suggest that the recently identified single
      nucleotide polymorphisms do not have a causal role for AITD in the UK. At this
      stage, we cannot exclude the Tg region as harboring a susceptibility locus for
      AITD, and only large scale sequencing and fine mapping of the region, including
      neighboring genes, will allow us to identify any potential causal variants within
      this region.

PMID- 15579801
TI  - A germline variation in the progesterone receptor gene increases transcriptional
      activity and may modify ovarian cancer risk.
AB  - Recently, we and others have detected a haplotype of the human progesterone
      receptor gene (PR). This haplotype consists of a 320-bp insertion in intron G
      together with point mutations in exons 4 and 5 and was named PROGINS. Whereas the
      exon 5 mutation is silent, the mutation in exon 4 results in a V660L
      substitution. Interestingly, this genetic polymorphism was seen to cosegregate
      with an increased risk of sporadic ovarian cancer in different ethnic groups. Our
      data provide evidence for the existence of an epidemiological link between a
      mutated progesterone receptor allele and ovarian cancer (odds ratio, 3.02; 95%
      confidence interval, 1.86-4.91). Functional characterization of the mutated
      receptor protein revealed a greater transcriptional activity compared with the
      wild-type receptor. By contrast, hormone binding and hormone dissociation rates
      were similar in both receptor proteins. We found that the increased
      transcriptional activity was due to increased stability resulting in higher
      expression of the mutant protein. Thus, the long-lasting hyperactivation of
      progesterone receptor-driven genes secondary to the increased transcriptional
      activity of the mutated progesterone receptor may participate in ovarian
      carcinogenesis. This is of special interest, because only a few genetic markers
      are available for the majority of women diagnosed with sporadic ovarian cancer.

PMID- 15579802
TI  - Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term
      results.
AB  - Untreated Cushing's disease and the resultant chronically elevated glucocorticoid
      levels lead to severe metabolic disturbances, including diabetes mellitus,
      obesity, hypertension, muscle wasting, and osteoporosis. Although transsphenoidal
      resection has become the standard of care for Cushing's disease with high initial
      success rates, little information is available on the long-term morbidity and
      mortality of patients in remission compared with patients with recurrent or
      persistent Cushing's disease after such treatment. We therefore conducted a
      retrospective study of 289 patients with Cushing's disease who underwent
      transsphenoidal microsurgery for an ACTH-secreting adenoma at a tertiary care
      center exclusively by one surgeon (C.B.W.). Postoperative remission was achieved
      in 82% (n = 236) of patients, with best initial remission rates observed in
      patients with grade I (86%) and II (83%) or stage 0 (88%), A (94%), and B (100%)
      tumors. Male gender, larger tumor size, and higher stage predicted poorer initial
      outcome. Long-term follow-up was obtained on 178 patients, with a median follow
      up time of 11.1 yr (range, 0.6-24.1 yr). Thirteen of 150 (9%) of patients in
      initial remission developed recurrent disease, and 12 patients underwent
      additional treatment. At last follow-up, only two of these patients had active
      disease. However, of the 28 patients with initial persistent disease who had
      follow-up greater than 6 months, 10 patients continued to have active disease at
      last follow-up. Although overall survival rates in patients with initial
      remission did not differ significantly from expected compared with the general
      population based on age and sex distribution, patients with initial persistent
      disease had a significant increase in mortality compared with the expected
      mortality. Thus, successful treatment of Cushing's disease is associated with
      normal long-term survival. These results suggest that patients with persistent
      Cushing's disease require early and aggressive intervention to attempt to prevent
      this excess mortality.

PMID- 15579803
TI  - AA2500 testosterone gel normalizes androgen levels in aging males with
      improvements in body composition and sexual function.

PMID- 15579804
TI  - Obesity-related glomerulopathy.

PMID- 15579805
TI  - Proscar and propecia--a therapeutic perspective.

PMID- 15579806
TI  - A differential dosage hypothesis for parental effects in seed development.

PMID- 15579808
TI  - Reading vocabulary knowledge and deafness.
AB  - With respect to reading vocabulary knowledge and deafness, this article addresses
      two broad questions: (1) Why is vocabulary knowledge related to reading
      comprehension ability? (2) How is reading vocabulary (i.e., word meanings)
      acquired? The article argues that the answers to these questions are best
      addressed by a vocabulary acquisition model labeled the knowledge model. In
      essence, this model asserts that both breadth and depth of vocabulary knowledge
      are critical. It is necessary to teach vocabulary, especially to poor readers,
      who are not likely to derive many word meanings from the use of context during
      natural or deliberate reading situations. On the basis of theoretical and
      research syntheses, the article offers implications for vocabulary instruction
      for deaf children and adolescents.

PMID- 15579809
TI  - Conceptualizing and conducting preoperative psychological assessments of cochlear
      implant candidates.
AB  - A review of literature pertaining to psychosocial research on cochlear
      implantation is embedded in this formulation of how preoperative psychological
      assessments should be comceptualized and conducted. This article considers
      various purposes of such assessments, including those relevant to candidate
      selection, exclusion, and readiness. Particular attention is directed to the
      conceptualization and operational investigation of candidate readiness, which
      includes aspects of motivation and informed consent. Assessment in this context
      is framed as both a data collection and an intervention procedure. The article
      describes specific methodologies useful in preoperative psychological assessment,
      including questionnaires, interviews, and psychological tests.

PMID- 15579807
TI  - The ubiquitin-proteasome pathway and plant development.

PMID- 15579810
TI  - The gap between guidelines, practice, and knowledge in interpreting services for
      deaf students.
AB  - In this article, we examine the literature on educational interpreting for
      information related to optimal interpreting in school settings. this literature
      review is coupled with an examination of 15 guidelines for educational
      interpreters in school districts and programs for the deaf and hard of hearing
      across the United States. With this information, we then explore discrepancies
      between what guidelines recommend, what actually occurs in classrooms, and what
      research on the process of interpreting has found on the basis of three major
      areas of concern: the production of the message by the interpreter, the reception
      of the message by the student, and additional responsibilities required of
      interpreters working in school programs.

PMID- 15579811
TI  - Deaf college students' perceptions of communication in mainstream classes.
AB  - Fifty deaf and hard-of-hearing students who were mainstreamed in postsecondary
      classes rated their classroom communication ease with hearing instructors,
      hearing peers, and deaf peers. A subgroup of these students participated in an in
      depth interview that focused on perceptions of communication ease, support
      services, and attitudes of teachers and students toward deaf students in
      mainstreamed classes. Quantitative analyses indicated that students more
      comfortable in using speech in this setting reported being able to receive and
      send a greater amount and a higher quality of information than did students who
      were less comfortable in using speech. Both quantitative and qualitative results
      indicated that students varied considerably in their communication with hearing
      peers and professors, in their relations with deaf peers, and in their concerns
      about access. It is a challenge for interpreting and other support services to
      serve these various needs, especially when it is not unusual for these variations
      to occur in the same classroom.

PMID- 15579812
TI  - The social adjustment of deaf adolescents in segregated parially integrated and
      mainstreamed settings.
AB  - This study examined the social adjustment of deaf adolescents enrolled in
      segregated (&egr; = 39), partially integrated (&egr; = 15), and mainstreamed
      (&egr; = 17) settings, comparing them with a control group of hearing students
      (&egr; = 88). Segregated students showed the lowest levels of adjustment overall.
      Partially integrated students reported better adjustment overall. Partially
      integrated students reported better adjustment than mainstreamed students with
      deaf peers; mainstreamed students reported better adjustment than partially
      integrated students with hearing peers, showing the same levels of adjustment
      with hearing peers as hearing students. Regardless of placement, deaf students
      reported better or equal adjustment with deaf than with hearing peers. Social
      adjustment with deaf peers was related to American Sign Language (ASL) skill and
      adjustment with hearing peers to spoken English. These findings suggest tht deaf
      students can benefit from both segregated and integrated placements as
      complememtary forms of social experience that each contribute to overal
      adjustment.

PMID- 15579813
TI  - Kitchen notes, 'the grapevine', and other writing in childhood.
AB  - In semistructured interviews, 20 men and 20 women (10 deaf and 10 hearing)
      between the ages of 18 and 28 recalled instances of instrumental, social, and
      expressive writing from their childhood. In contrast to earlier research, we
      found that instrumental writing occurred as frequently between deaf children and
      their hearing parents as between deaf children and their deaf parents and that
      all homes with a deaf family member had telecommunication devices for the
      deaf(TTYs). Whereas all respondents engaged in some form of social writing, deaf
      respondents did less personal or expressive writing than their hearing peers.
      Implications for literacy instruction and further research are that (a) teachers
      should take advantage of the writing experience that students bring to the
      classroom, (b) writing should be used as a tool for learning and classroom
      communication, and (c) the effects of experience, genre, school setting, and
      technology on the writing of deaf students should be examined.

PMID- 15579814
TI  - The interaction of syntactic competence and vocabulary during reading by deaf
      students.
AB  - This research studied whether deaf students' component reading processes may
      interact with other in a competitive manner. Vocabulary and syntax, two processes
      known to directly and adversely affect the comprehension of many deaf readers,
      were studied to determine if they may influence each other, affecting the
      contribution that each one makes separately to reading comprehension. Multiple
      regression analyses were conducted on predictor variables that included measures
      of vocabulary and syntactic competence, as well as a variable summarizing the
      interaction of vocabulary and syntax. The criterion variable was a composite of
      comprehension performance on a cloze procedure and on a more traditional reading
      test. Results were cross-validated by separate regressions on data samples from
      three populations of profoundly deaf readers: 100 adolescents from oral school
      programs, 113 adolescents from total communication programs, and 211 students
      entering a postsecondary institution that used total communication. In each
      regression, the Vocabulary &times; Syntax interaction variable emerged as the
      most critical of the three predictors. Further analyses of the interaction
      revealed that among subjects in the highest quartile of syntactic competence, the
      correlation between vocabulary competence and reading was significantly greater
      than it was in the lower three syntax quartiles. In contrast, the relationship
      between syntax and comprehension remained stable across all four quartiles of
      vocabulary competence. This suggests that unless deaf readers have achieved a
      reasonable level of syntactic competence it may be difficult for them to
      capitalize fully on their vocabulary knowledge. The finding that limitations in
      one reading process can interfere with the application of another is consistent
      with the theory of Capacity Constrained Comprehension of M. Just and P. Carpenter
      (1992). Because syntax can exert both a direct and an indirect influence on
      comprehension, it should be an important focus in instructional programs.

PMID- 15579815
TI  - Can the linguistic interdependence theory support a bilingual-bicultural model of
      literacy education for deaf students?
AB  - Drawing on Cummins' (1989) linguistic interdependence model, proponents of
      bilingual-bicultural models of literacy education for deaf students claim that,
      if ASL is well established as the L1, then literacy in English (L2) can be
      achieved by means of reading and writing without exposure to English through
      either speech or English-based sign. In our opinion, this claim is based on a
      false analogy: the situation of the deaf learner of English literacy does not
      match the conditions assumed by the linguistic interdependence model. We draw on
      the work of Vygotsky and Halliday to develop a conceptualization of the processes
      involved in becoming literate, examining the particular and unique challenges
      that deaf students face as they strive to become members of the linguistic
      community of users of written English. We argue that becoming literate involves
      mastering three modes of lanuage use: 'social speech,' 'inner speech,' and
      written text. In some respects the educational context for deaf students is
      analogous to that of other bilingual learners; in some crucial aspects, it is
      very different.

PMID- 15579816
TI  - The development of spoken language in deaf children: explaining the unexplained
      variance.
AB  - Using a large existing data base on children with severe and profound deafness,
      10 children were identified whose level of spoken laguage was most above and 10
      whose level was most below that expected on the basis of their hearing loss, age,
      and intelligence. A study of their personal characteristics, family background,
      and educational history identified factors associated with unusually high
      performance; these includes earlier use of binaural ear-level aids, more highly
      educated mothers, auditory/verbal or auditory/oral instruction, reliance on
      spoken language as a method of communication, individualized instruction,
      integration, and structured teaching by parents. Parents of high performers also
      reported being highly commited to and focusing family resouces on developing
      their child's spoken language.

PMID- 15579817
TI  - Language codes and sense-making among deaf schoolchildren.
AB  - There are at least two languages (American Sign Language [ASL], English) and
      three modalities (sign, speech, print) in most deaf individuals' lives. Mixing of
      ASL and English in utterances of deaf adults has been described in various ways
      (pidgins, diglossia, language contact, bilingualism), but children's mixing
      usually is treated as the 'fault' of poor input language. Alternatively, how
      might language mixing serve their communication goals? This article describes
      code variations and adaptations to particular situations. Deaf children were seen
      to exhibit a wide variety of linguistic structures mixing ASL, English, Spanish,
      signing, and speaking. Formal lessons supported a recoding of English print as
      sign and speech, but the children who communicated English speech were the two
      who could hear speech. The children who communicated ASL were those who had deaf
      parents communicating ASL or who identified with deaf houseparents communicating
      ASL. Most language produced by the teacher and children in this study was mixed
      in code and mode. While some mixing was related to acquisition and proficiency,
      mixing, a strategy of many deaf individuals, uniquely adapts linguistic resources
      to communication needs. Investigating deaf children's language by comparing it to
      standard English or ASL overlooks the rich strategies of mixing that are central
      to their communication experience.

PMID- 15579818
TI  - Motivational and attitudinal orientations in learning American Sign Language.
AB  - Integrative motivation was found to correlate significantly with sign language
      proficiency of adult learners at a post-secondary program for deaf students.
      Instrumental motives, however, were perceived as less important. Higher
      achievement in ASL was also associated with a positive cultural attitude toward
      deaf people. Learning of ASL as a second language may be enhanced if instructors
      design strategies that build upon these cultural and integrative motives and
      provide rewarding experiences to adult learners.

PMID- 15579819
TI  - Does deafness lead to enhancement of visual spatial cognition in children?
      Negative evidence from deaf nonsigners.
AB  - This study investigated whether deafness contributes to enhancement of visual
      spatial cognition independent of knowledge of a sign language. Congenitally deaf
      school children in India who were born to hearing parents and were not exposed to
      any sign language, and matched hearing controls, were given a test of digit span
      and five tests that measured visual spatial skills. The deaf group showed shorter
      digit span than the hearing group, consistent with previous studies. Deaf and
      hearing children did not differ in their performance on the visual spatial skills
      test, suggesting that deafness per se may not be a sufficient factor for
      enhancement of visual spatial cognition. Early exposure to a sign language and
      fluent sign skills may be the critical factors that lead to differential
      development of visual spatial skills in deaf people.

PMID- 15579820
TI  - Stress and coping in families with deaf children.
AB  - More than 90% of deaf children are born to hearing parents who experience stress,
      not only in respose to the initial diagnosis, but also in adapting to the unique
      needs of their deaf child. This article is a selective literature review
      summarizing information from three fields in order to broaden our understanding
      of family adaptation to deafness. Discussion includes (1) psychology's model of
      individual stress and coping (2) family science's model of family stress
      management, and (3) literature on family adjustment to disability. The last part
      of the article traces the development of professionals' understanding of the
      reciprocal influences between deaf children and their families and describes
      recent research indicating that the impact of deafness on families is complex and
      variable. The final conclusion is that adoption of a family stress and coping
      paradigm would inform discussion of current issues in deafness, such as cochlear
      implants and bilingualism/biculturalism.

PMID- 15579821
TI  - Validity of indirect assessment of writing competency for deaf and hard-of
      hearing college students.
AB  - Indirect tests of writing competency are often used at the college level for a
      variety of educational, programmatic, and research purposes. Although such tests
      may have been validated on hearing populations, it cannot be assumed that they
      validly assess the writing competency of deaf and hard-of-hearing students. This
      study used a direct criterion measure of writing competency to determine the
      criterion validity of two indirect measures of writing competency. Results
      suggest that the validity of indirect writing tests for deaf and hard-of-hearing
      baccalaureate-level students is weak. We recommend that direct writing tests be
      used with this population to ensure fair and accurage assessment of writing
      competency.

PMID- 15579822
TI  - Theory of mind in deaf adults and the organization of verbs of knowing.
AB  - Naive theories of mind provide an organizing scheme for concept formation and
      categorization. Additionally, they highlight what is important within a domain.
      This study investigated how deaf adults with hearing parents orgaize 17 cognitive
      verbs of knowing as a way of describing their naive theory of mind. Deaf adults
      rated on 1 to 7 scale the similarity of pairs of cognitive verbs in terms of
      whether 'the words are alike or different based on how you would use your mind
      when you do that mental activity'. We directly compared the similarity of
      cognitive verbs in these deaf adults with data collected in earlier research
      describing the organisation of cognitive verbs in hearing adults. We conducted
      multidimensional scaling, additive similarity tree, and Pathfinder analyses to
      assess global, categorical, and local relations in the domain. Deaf adults'
      theory of mind revealed distinction among mental verbs in terms of information
      processing components and constructive certainty components. In all analyses, the
      deaf group showed a very similar organization to that of hearing adults examined
      in previous research. We conclude that, although deaf adults might be expected to
      view congnitive processes differently than hearing adults, they nonetheless
      exhibit a theory of mind that is highly similar to that of hearing adults.

PMID- 15579823
TI  - Verbal information-processing capabilities and cochlear implants: implications
      for preoperative predictors of speech understanding.
AB  - In this study, we examined preoperative verbal cognitive capacity in 11 deafened
      adults who were cochlear implant candidates and reexamined level of speech
      understanding after 6-8 months' experience with the implant. Verbal cognitive
      performance in the implant group was compared in a group of normal hearing
      subjects and in nonimplanted group of deafened adults. The three groups performed
      on par with each other with an exception: The individuals in the cochlear implant
      group and the nonimplanted group of deafened adults performed significatly worse
      than those of normal hearing in tasks in which use of internal speech is a key
      feature (i.e., rhyme judgement and lexical decision tasks). Postoperative
      observations of the implanted individuals' level of speech understanding suggest
      that it is possible to predict the level of speech understanding by means of a
      properative cognitive assessment. The characteristics of three verbal cognitive
      abilities prove to be critical indicators of 6 - 8 months' postoperative outcome:
      internal speech functioning, speed of verval information processing, and working
      memory capacity - the first factor proved the most decisive. We discuss the
      results with respect to direct versus indirect predictors of outcomes from
      cochlear implant operations and the effect of auditory deprivation on deafened
      adults' capability to process auditory information.

PMID- 15579824
TI  - Motivational factors in learning American sign lanquage.
AB  - This study focuses on factors that motivate and demotivate professionals to learn
      American Sign Language (ASL). Using a qualitative approach known as the Critical
      Incident Technique (CIT), faculty and staff were asked to reflect on their sign
      language learning expericences, and their responses were examined for
      motivational patterns. Principal motivating factors were intrinsic in nature,
      including a desire to perform well in one's position, personal goals, and an
      interest in sign language per se. Integrative factors were also important,
      especially an interest in social interactions with deaf people. Principal factors
      that demotivated the respondents were more extrinsic in nature, dealing with
      workload, scheduling issues associated with the sign language curriculum,
      instruction, and the attitudes of self and others. We draw implications from the
      findings for the enhancement of sign language instruction programs.

PMID- 15579825
TI  - Special issue on cognition and development.

PMID- 15579826
TI  - Deafness, story understanding, and theory of mind.

PMID- 15579827
TI  - Visual speech in the head: the effect of cued-speech on rhyming, remembering, and
      spelling.

PMID- 15579828
TI  - Varieties of short-term memory coding in deaf teenagers.

PMID- 15579829
TI  - Cognitive processes of deaf and hearing skilled and less skilled readers.

PMID- 15579830
TI  - On language deficits and modality in children with Down syndrome: a case study of
      twins bilingual in BSL and English.

PMID- 15579831
TI  - Revisiting history: on bridging research and teaching.

PMID- 15579832
TI  - Visual-kinetic communication in Europe before 1600: a survey of signs lexicons
      and finger alphabets prior to the rise of deaf education.
AB  - Visual-kinetic communication systems - ancient finger numbers, medieval and
      Renaissance finger alphabets, conventionalized 'coverbal' gesture systems for
      oratory and the theater, the Roman pantomime, monastic sign lexicons, and the
      elusive possibility of natural sign languages - have all received the scholarly
      attention that has turned up the few surviving primary texts from the period
      before 1600. The extant documentation indicates that many visual-kinetic systems
      were sporadically in use among the general (i.e., hearing) population to a degree
      almost unimaginable to post-Renaissance societies such as ours that popularly
      associate 'gesture languages' with the deaf. In detail, however, the texts are
      often difficult to interpret, not only because of their scarcity and generally
      highly allusive nature, but also because of modern historians' often unproductive
      or misproductive approaches to them. This survey is meant to provide an overview
      of the textual evidence and a foundation for both sign language linguists and
      historians of the deaf education to analyze and interpret more accurately and
      usefully the extant evidence for visual-kinetic communication systems before the
      rise of Deaf Education.

PMID- 15579833
TI  - Effects of mother and infant hearing status on interactions at twelve and
      eighteen months.
AB  - Eighty mother-infant dyads, evenly distributed among the four possible hearing
      status combinations, were videotaped during free play when infants were 12 months
      old and again when they were 18 months old. Pairs of trained observers evaluated
      interactive behaviors for mothers, infants, and dyads. At time 1, hearing mothers
      and deaf infants ranked lowest, hearing mothers and hearing infants ranked
      highest, with the two deaf-mother groups intermediate. At time 2, deaf mothers
      and hearing infants received more negative rankings, leading to concern for the
      effect of mismatched hearing status regardless of the functional capabilities of
      mothers and infants to communicate in a mutually comprehensible mode. Discussion
      focuses on possible explanations for the negative influence of hearing status
      differences.

PMID- 15579834
TI  - A study of the relationship between American sign language and English literacy.
AB  - This article presents the findings of a study of the relationship between
      American Sign Language (ASL) skills and English literacy among 160 deaf children.
      Using a specially designed test of ASL to determine three levels of ASL ability,
      we found that deaf children who attained the higher two levels significantly
      outperformed children in the lowest ASL ability level in English literacy,
      regardless of age and IQ. Furthermore, although deaf children with deaf mothers
      outperformed deaf children of hearing mothers in both ASL and English literacy,
      when ASL level was held constant, there was no difference between these two
      groups, except in the lowest level of ASL ability. The implication of this
      research is straightforward and powerful: Deaf children's learning of English
      appears to benefit from the acquisition of even a moderate fluency in ASL.

PMID- 15579835
TI  - Effect of teacher questions on the reading comprehension of deaf children.
AB  - We examined the effect of comprehension questions that require analysis,
      synthesis, and evaluation on the reading comprehension of deaf children. The
      subjects were six deaf children ranging in age from 10 years, months to 12 years,
      5 months. They were divided into four reading groups for the study. Quantitative
      analysis of the children's responses to comprehension questions indicated that
      the children could analyze, synthesize, and evaluate narrative text and their
      ability to do so did not need to be supported by answering questions related to
      story details. Qualitative analysis indicated that the children had some
      difficulty with seven reading tasks: locating pertinent information, applying
      relevant and accurate background knowledge, expressing themselves unambiguously,
      understanding the intent of the question, not relying too heavily or too little
      on background knowledge, considering consequential details, and providing
      sufficient answers.

PMID- 15579836
TI  - The effect of the method of repeated readings on the reading rate and word
      recognition accuracy of deaf adolescents.
AB  - This study examined the effects of the method of repeated readings (RR), a well
      accepted remedial reading technique for improving the reading rate of hearing
      children, with deaf adolescents. Forty-two students from a midwestern residential
      school for the deaf were randomly assigned into treatment and control groups. The
      groups were equivalent with respect to age, level of hearing loss, reading
      achievement, and mental ability. All subjects read material previously determined
      to be at their instructional levels. Members of the treatment group were
      videotaped during the initial reading of an assigned passage, allowed to practice
      over three 15-minute sessions, then videotaped again during a final reading of
      the assigned passage. The control group differed only in that it practiced
      reading material other than the assigned passage. Reading rates and word
      recognition accuracy were recorded for the initial and final reading of each of
      five passages. Results indicated that the treatment subjects demonstrated
      significant improvement between pre- and posttesting regarding reading rate and
      two measures of word recognition accuracy. The performance of subjects engaged in
      nonrepetitive reading demonstrated minimal improvement. We discuss applicability
      of this procedure with a deaf population and implications for future research and
      practice.

PMID- 15579837
TI  - Valid assessment of writing and access to academic discourse.
AB  - One way to improve students' access to and retention in post-secondary degree
      progams is to assess their readiness for such programs accurately. To place deaf
      and hard-of-hearing students in preparatory courses and to determine their
      readiness for degree programs more accurately, a direct measure of writing was
      developed for deaf and hard-of-hearing students at a large technical university.
      The purpose of this study was to estimate the concurrent and predictive validity
      of this measure. The Test of Written English (Educational Testing Service, 1992)
      served as the criterion in the concurrent validity study, and student success in
      the university's gateway freshman composition course served as the criterion in
      the predictive validity study. Results provide evidence of the concurrent and
      predictive validity of the measure, supporting its use for course placement and
      early planning purposes.

PMID- 15579838
TI  - Working memory capacity and comprehension processes in deaf readers.
AB  - This research studied deaf students' performance on memory span and component
      reading tasks that incorporated processes involved in higher level comprehension.
      The instruments developed in the study provide the basis for the measurement of
      functional working memory capacity, vocabulary knowledge, domain-relevant
      knowledge, and inference abilities. Multiple regression analysis was used to
      construct models that show the contributions of the independent assessments to
      reading comprehension ability. Overall results suggest that working memory
      operates as a general executive system, as indicated by significant correlations
      between subjects' performance on reading and nonreading tasks. Limitations in
      vocabulary knowledge continue to pose problems in reading for deaf individuals.
      General or procedural knowledge also plays a part in reading comprehension
      processes.

PMID- 15579839
TI  - Learning to look in the right place: a comparison of attentional behavior in deaf
      children with deaf and hearing mothers.
AB  - Eleven 18-month-old children with profound prelingual hearing loss were video
      recorded in a free-play session with their mothers. Five of the mothers were
      profoundly deaf and fluent users of British Sign Language (BSL) or Auslan. The
      other six were hearing and had enrolled in a signing program. Ten-minute segments
      from each session were analyzed to determine the number of switches in attention
      shown by each child. Switches in attention were subdivided into three categories:
      spontaneous (where the child spontaneously looked to the mother); responsive
      (where the child responded to some maternal action such as moving an object); and
      elicited (where the mother made a direct attempt to gain the child's attention.
      Failed attempts to gain attention were also noted. A comparison of deaf and
      hearing mothers revealed no difference in the proportion of spontaneous or
      responsive switches in attention shown by their children. Responsive switches
      were by far the most frequent category for both groups, but these most commonly
      focused on objects and did not provide an opportunity for maternal signing.
      Successful perception of signing typically followed from spontaneous or elicited
      attentional switches. Deaf mothers were generally more insistent on their
      children turning to look at them, and they were more successful in eliciting
      attentional switches although they also had more failed attempts. These overall
      differences between the two groups were overshadowed by large individual
      differences within the groups. Within the sample there were both deaf and hearing
      mothers who achieved successful signed communication with their children.

PMID- 15579840
TI  - What mothers do to support infant visual attention: sensitivities to age and
      hearing status.
AB  - This article presents a descriptive, longitudinal study of maternal use of
      communicative strategies to accommodate and direct infant visual attention. The
      two questions that guided our research were whether maternal use of particular
      attention-related strategies changed as the child developed from 9 to 18 months
      of age and whether the mother's ability to make appropriate modifications in
      strategy use was disrupted when she was using a new mode of communication. Four
      groups of mother-infant dyads were included: deaf mothers with deaf children
      (Dd), hearing mothers with deaf children (Hd), deaf mothers with hearing children
      (Dh), and hearing mothers with hearing children (Hh) (n = 77). When the infants
      were 9, 12, and 18 months old, they were videotaped while they engaged in free
      play with their mothers. Using a time-sampling technique, videotapes were coded
      to determine the frequency with which mothers used specific attention-related
      strategies. Our findings showed group differences in the attention-related
      strategies used by deaf and hearing mothers. These group differences were
      consistent with the hypothesis that while mothers appeared to be sensitive to and
      tried to accommodate their children's communication needs, the mothers may have
      been limited by their own communicative experiences. With regard to changes in
      mothers' use of attention-related strategies over time, our hypothesis of a
      developmental transition in the chosen strategies was only partially supported.
      Attention strategies related to language did evidence a pattern of developmental
      progression; however, maternal use of strategies that directed the children's
      visual focus to an object or a social partner did not show any such trend.
      Overall, the patterns indicated in the data from this study suggest that
      bidirectional influences were operating to some degree in each of the four
      groups. Among mothers whose hearing status differs from their children, the use
      of certain attention-related strategies might need to be taught, particularly the
      use of specific strategies that may scaffold deaf infants' developing abilities
      to alternate attention between objects and persons.

PMID- 15579841
TI  - Working memory for sign language: a window into the architecture of the working
      memory system.
AB  - Traditionally, working memory has been divided into two major domains: verbal and
      visuo-spatial. The verbal domain of working memory can be characterized either by
      its relationship to language or by its grounding in auditory processing. Because
      of this ambiguity, languages that are not auditory and vocal (i.e., signed
      languages) pose a challenge to this conception of working memory. We describe
      several experiments with deaf users of American Sign Language (ASL) that explore
      the extent to which the architecture of working memory is determined by the
      constraints of auditory and visual processing and the extent to which it is
      determined by the characteristics of language. Various working memory effects
      were investigated: phonological similarity, word length, and articulatory
      suppression. The pattern of evidence strongly supports the existence of a sign
      based 'rehearsal loop' mechanism parallel to the speech-based rehearsal loop.
      However, we also discuss evidence pointing to differences between the speech loop
      and the sign loop from forward and backward digit span tasks with deaf and
      hearing subjects. Despite their similarities based on linguistic properties, the
      speech loop and the sign loop appear to diverge due to the differing processing
      demands of audition and vision. Overall, the results suggest that the
      architecture of working memory is shaped both by the properties of language
      structure and by the constraints imposed by sensorimotor modality.

PMID- 15579842
TI  - Deafness, language skills, and rehearsal: a model for the development of a memory
      strategy.
AB  - We review a series of studies that evaluate the role of developing language
      skills as a prerequisite to spontaneous rehearsal use in deaf populations. We
      propose a theoretical model that summarizes the contribution of language skills
      by highlighting the interrelations among age, language proficiency, and
      automatized language skills. In an initial test of the model, an index of deaf
      children's language experience was found to be an almost complete mediator of
      strategy use. Increasing language proficiency, therefore, was implicated as a
      critical variable in predicting children's spontaneous rehearsal use, minimizing
      any direct contribution from age per se. In a more direct assessment of the link
      between general language proficiency and rehearsal use, pragmatic language skills
      (as measured by the Language Proficiency Profile: LPP-I) were found to be a
      nearly complete mediator of rehearsal use, with the remaining contributions of
      age and language experience being nonsignificant. Language proficiency,
      therefore, was identified as a strong and necessary prerequisite for rehearsal to
      be used spontaneously as a memory strategy. The additional hypothesis that the
      automatization of these general language skills, measured by a rapid automatized
      naming task (RAN), contributes to spontaneous rehearsal was also evaluated.
      Automatized language emerged as a partial mediator of the language proficiency
      &rarr; rehearsal use relation but additional language-processing variables were
      implicated. We discuss these findings as they relate to issues around the nature
      of language proficiency and the identification of those automatized language
      skills involved in rehearsal.

PMID- 15579843
TI  - Metacognition and reading in children who are deaf: a review of the research.
AB  - The purpose of this article is to review and synthesize the literature linking
      metacognition and reading in children who are deaf. Although this body of
      research is sparse, three issues emerge. First, the research implies that current
      instructional practices used to teach reading to deaf children might actually
      hinder their development of mature metacognitive knowledge and control. Second,
      the studies suggest that the low-level reading material typically given to deaf
      children might not provide the opportunity for them to develop, practice, or use
      metacognitive strategies. And third, the research shows that deaf students can
      benefit from metacognitive strategy instruction.

PMID- 15579844
TI  - Modality of language shapes working memory: evidence from digit span and spatial
      span in ASL signers.
AB  - Deaf children who are native users of American Sign Language (ASL) and hearing
      children who are native English speakers performed three working memory tasks.
      Results indicate that language modality shapes the architecture of working
      memory. Digit span with forward and backward report, performed by each group in
      their native language, suggests that the language rehearsal mechanisms for spoken
      language and for sign language differ in their processing constraints. Unlike
      hearing children, deaf children who are native signers of ASL were as good at
      backward recall of digits as at forward recall, suggesting that serial order
      information for ASL is stored in a form that does not have a preferred
      directionality. Data from a group of deaf children who were not native signers of
      ASL rule out explanations in terms of a floor effect or a nonlinguistic visual
      strategy. Further, deaf children who were native signers outperformed hearing
      children on a nonlinguistic spatial memory task, suggesting that language
      expertise in a particular modality exerts an influence on nonlinguistic working
      memory within that modality. Thus, language modality has consequences for the
      structure of working memory, both within and outside the linguistic domain.

PMID- 15579845
TI  - Does sign language provide deaf children with an abstraction advantage? Evidence
      from a categorization task.
AB  - The effects of sign language use on cognitive processes of second-generation deaf
      children were investigated through an intensional categorization task. A forced
      choice paradigm was used to examine children's selections of schematic and
      categorical alternatives as associations to targets that differed in their
      related sign language characteristics. The results obtained from 48 deaf and
      hearing 6-year-olds suggest some differences in the categorization abilities and
      cognitive flexibility between the two groups of children. These differences
      appear to be explainable in terms of linguistic variables underlying French Sign
      Language.

PMID- 15579846
TI  - Prior knowledge and reading comprehension ability of deaf adolescents.
AB  - Fifty-one severely to profoundly deaf students (mean dB hearing loss = 89) were
      randomly assigned to two groups that differed by the type of probes (short or
      long) used to elicit prior knowledge (PK). PK scores were used to predict reading
      comprehension (RC), which was assessed by students' responses to three types of
      questions: test-explicit (TE), text-implicit (TI), and script-implicit (SI).
      Multiple regression models with PK scores and scores from a standardized
      achievement test (Stanford Achievement Test - Hearing Impaired Version, reading
      subtest) were also used to predict RC. The regression model showed that, for the
      group pretested with an in-depth, or long, probe of PK, the best predictor of RC
      was the ability to answer TE and SI questions. We present discussions of the
      observed differences in comprehension as a function of long and short knowledge
      probes and the use of three question types, together with implications for
      instruction.

PMID- 15579847
TI  - Deaf children's understanding of beliefs and desires.
AB  - Twenty-two children (5-12 year old) who were profoundly, prelingually deaf were
      given two tests designed to tap their 'theory of mind', that is, their ability to
      attribute independent mental states to other people. The tests were versions of
      Baron-Cohen, Leslie, and Frith's Sally-Anne task and of Baron-Cohen's breakfast
      task. Seventy percent of the children were successful on all questions requiring
      belief attribution, a considerably and significantly larger percentage than the
      29% obtained by Peterson and Siegal for a similar sample, though it is still
      lower than would be expected on the basis on chronological age. Children were
      universally successful on questions requiring the attribution of desire. We
      discuss implications of the findings.

PMID- 15579848
TI  - The structure and optimization of speechreading.
AB  - Erber (1988) has claimed that one of the reasons for the ascendancy of hearing
      aids has been the loss of confidence in speechreading. Speechreading can be of
      value to those suffering from presbyacusis and other hearing disorders, in
      augmenting hearing aids and cochlear implants, for large numbers of people in
      developing countries who are unable to afford electronic aids, and for those in
      advanced countries who are reluctant to wear an aid. I discuss the structure and
      the optimization of speechreading. New methods to optimize natural speechreading
      skills are required that must be based on the structure and nature of
      speechreading. It has been suggested that speechreading is, to some extent,
      innate, and so 'hard-wired', which would mean that the effect of long-term
      training is limited. I critique this view and present a macro-analysis of the
      experimental literature. I suggest that the innate view may be somewhat
      overstated.

PMID- 15579849
TI  - Face processing by deaf ASL signers: evidence for expertise in distinguished
      local features.
AB  - Several previous studies have shown that ASL signers are 'experts' on at least
      one test of face processing: the Benton Test of Face Recognition, a
      discrimination task that requires subjects to select a target face from a set of
      faces shown in profile and/or in shadow. The experiments reported here were
      designed to discover why ASL signers have superior skill as measured by this test
      and to investigate whether enhanced performance extends to other aspects of face
      processing. Experiment 1 indicated that the enhancement in face-processing skills
      does not extend to recognition of faces from memory. Experiment 2 revealed that
      deaf and hearing subjects do not differ in their gestalt face-processing ability;
      they perform similarly on a closure test of face perception. Finally, experiment
      3 suggested that ASL signers do exhibit a superior ability to detect subtle
      differences in facial features. This superior performance may be linked both to
      experience discriminating ASL grammatical facial expression and to experience
      with lipreading. We conclude that only specific aspects of face processing are
      enhanced in deaf signers: those skills relevant to detecting local feature
      configurations that must be generalized over individual faces.

PMID- 15579850
TI  - Enhanced facial discrimination: effects of experience with American sign
      language.
AB  - On-line comprehension of American Sign Language (ASL) requires rapid
      discrimination of linguistic facial expressions. We hypothesized that ASL
      signers' experience discriminating linguistic facial expressions might lead to
      enhanced performance for discriminating among different faces. Five experiments
      are reported that investigate signers' and non-signers' ability to discriminate
      human faces photographed under different conditions of orientation and lighting
      (the Benton Test of Facial Recognition). The results showed that deaf signers
      performed significantly better than hearing non-signers. Hearing native signers
      (born to deaf parents) also performed better than hearing nonsigners, suggesting
      that the enhanced performance of deaf signers is linked to experience with ASL
      rather than to auditory deprivation. Deaf signers who acquired ASL in early
      adulthood did not differ from native signers, which suggests that there is no
      'critical period' during which signers must be exposed to ASL in order to exhibit
      enhanced face discrimination abilities. When the faces were inverted, signing and
      nonsigning groups did not differ in performance. This pattern of results suggests
      that experience with sign language affects mechanisms specific to face processing
      and does not produce a general enhancement of visual discrimination. Finally, a
      similar pattern of results was found with signing and nonsigning children, 6-9
      years old. Overall, the results suggest that the brain mechanisms responsible for
      face processing are somewhat plastic and can be affected by experience. We
      discuss implications of these results for the relation between language and
      cognition.

PMID- 15579851
TI  - The effects of discourse genre on English language complexity in school-age deaf
      students.
AB  - This study explored the effects of discourse genre on the complexity of English
      language produced by school-age deaf students. Subjects were 13 profoundly deaf
      students, ages 7;1 to 14;8, who had been educated using only an English-based
      sign system in public schools. Language samples were elicited in three
      conditions: a traditional spontaneous interaction, a narrative elicitation using
      pictures, and an interview in which the examiner asked cognitively and
      linguistically challenging questions. The results show that students produced the
      most complex English language during the interview, as measured by the use of
      embedded clauses, conjunctions, and modals. In contrast to previous studies,
      utterance length in this one did not vary as a function of sample type, likely
      because segmentation of the samples was based on the T-unit, not sentences. The
      results have implications for language sampling with school-age students, both in
      terms of efficacy and ecological validity.

PMID- 15579852
TI  - Balancing between deaf and hearing worlds: reflections of mainstreamed college
      students on relationships and social interaction.
AB  - This qualitative study of the social aspects of mainstreaming from the
      perspective of deaf college students indicates that for some students, social
      adjustment to college is complicated by experiences of separation and alienation
      from both deaf and hearing peers. Data were collected through open-ended
      interviews with deaf students who had little or no previous experience with or
      exposure to deaf culture or language before their arrival at a mainstream college
      environment. Feelings of isolation, loneliness, and resentment were most intense
      during orientation and first year, when alienation from the deaf student
      community appeared to be caused by lack of sign language skills, unfamiliarity
      with norms and values of deaf culture, and perceived hostility from deaf peers.
      Simultaneous experiences of separation from hearing peers appeared to be caused
      by physical barriers inherent in the classroom, residence hall, and cafeteria
      environments, as well as by discrimination from hearing peers, who tended to
      stereotype deaf students. Findings suggest that those involved in the
      administration and delivery of postsecondary programs for the deaf should
      investigate the experiences of students who arrive on campus without knowledge of
      sign language or familiarity with deaf culture and evaluate currently existing
      programs and services designed to meet these students' needs.

PMID- 15579853
TI  - Conceptualizing parents' sign language use in bilingual early intervention.
AB  - This research study investigates how parents and interveners conceptualize
      parents' early sign language use. Three groups of respondents involved in the
      same bilingual early intervention program were being interviewed: hearing parents
      (n = 12), hearing teachers (n = 6), and Deaf consultants (n = 6). The search and
      retrieve program 'The Ethnograph' was used for data analysis. The results
      demonstrate that neither a framework of linguistic proficiency nor one of
      communicative competence captures the complexity of the issues involved for
      parents and interveners in conceptualizing parents' early sign language use. The
      interpretative frameworks of each group emphasize different aspects of the task
      facing parents: balancing the quest for Sign Language proficiency with emotional
      and practical considerations in the family, acknowledging the overriding
      importance of communication regardless of what one may label the language used,
      and confirming the visual quality and child appropriateness of the signing.
      Results are related to the stocks of knowledge on which respondents draw and the
      implications for Deaf and hearing interveners assessing parents' progress.

PMID- 15579854
TI  - Learning, language, memory, and reading: the role of language automatization and
      its impact on complex cognitive activities.
AB  - Two related models of the role of developing and automatized language skills in
      the cognitive processing of deaf and hearing children are presented. One model
      focuses on explaining apparent delays in the emergence of a memory strategy
      (cumulative rehearsal) in children who are deaf, linking strategy use with the
      child's emerging language skills and the automatization of those skills. The
      second model is larger in scope and integrates this rehearsal model with added
      components relevant for higher-level cognitive activities such as reading. A
      program of research is reviewed that provides support for various components of
      the models with deaf children. Implications of the models for potential
      concurrent learning disabilities are discussed.

PMID- 15579855
TI  - Considerations, conceptualizations, and challenges in the study of concomitant
      learning disabilities among children and adolescents who are deaf or hard of
      hearing.
AB  - In recent years, there has been increasing concern about the identification of
      and provision of appropriate services to children and adolescents who are deaf
      and hard of hearing (D/HH) and who have concomitant learning disabilities (LD).
      Although it is unclear just how many youths who are D/HH also might have
      educationally significant learning problems, results from limited survey research
      and clinical practice provide evidence that such a group exists and that a
      significant portion of the school-age population of children and adolescents who
      are D/HH comprise a subgroup of youths who have concomitant LD. The overriding
      interest of those who advocate the cause of children and adolescents who are D/HH
      with concomitant LD is in finding effective ways to help these youths acquire
      future academic competence and attain competent levels of psychosocial
      functioning and emotional well-being. With creative research efforts and
      efficacious approaches to psychoeducational practice, we can seize the
      opportunity to establish high-quality diagnostic and educational services for
      children and adolescents who are D/HH and who have accompanying LD and set the
      stage to optimize positive developmental, academic, vocational, social, and
      economic outcomes for these youths.

PMID- 15579856
TI  - Studies of neural processing in deaf signers: toward a neurocognitive model of
      language processing in the deaf.
AB  - The ability to comprehend and produce language stands as a defining
      characteristic of human cognition and enables the transfer of knowledge and
      culture within human society. A proper characterization of the human capacity for
      language is required for the development of interventions that may be used to
      assist those individuals who have failed to achieve, or who have lost competence
      in, language behaviors. For signed languages, models of competent language use
      are lacking. This lack of knowledge hampers the development of effective
      assessment measures for deaf children who may be experiencing learning problems
      beyond those confronting the normal deaf child. I discuss two research avenues
      that have begun to provide a window into the neural systems involved in sign
      language processing: studies of language disruptions in adult deaf signers who
      have suffered brain injury, and studies of functional brain imaging in normal
      deaf signers. This research provides a basis for the development of a
      comprehensive neurocognitive model of sign language processing.

PMID- 15579857
TI  - Preventive intervention for school-age deaf children: the PATHS curriculum.
AB  - This study examined the effectiveness of the PATHS (Promoting Alternative
      THinking Strategies) Curriculum on the social, cognitive, and behavioral status
      of elementary school-age deaf children. PATHS, a school-based preventive
      intervention model, was designed to improve children's self-control, emotional
      understanding, and problem-solving skills. The intervention field trial included
      a quasi-experimental, wait-list control design involving 57 children in 11 self
      contained classrooms utilizing Total Communication. Teachers were trained in the
      intervention model and provided PATHS lessons during most of one school year.
      Results indicated that the intervention led to significant improvement in
      students' social problem-solving skills, emotional recognition skills, and
      teacher- and parent-rated social competence. There was no effect in this
      normative sample on teacher- or parent-rated psychopathology. One-and-two-year
      posttest results indicated maintenance of effects. Results on the wait-list
      control group indicated replication of effects in a second sample. Discussion
      focused on the nature of change in school-based prevention trials.

PMID- 15579858
TI  - Theoretical and epidemiological aspects of attention deficit and overactivity in
      deaf children.
AB  - Disorders of attention deficit and overactivity, ADHD (DSM-IV), and hyperkinetic
      syndrome (ICD-10) are common and disabling. However, a number of factors in deaf
      children's development make the assessment of these disorders in deaf children
      problematic. The prevalence of ADHD and hyperkinetic disorder does not appear to
      be higher than expected in children with inherited deafness alone but does appear
      to be higher in children with acquired deafness and/or additional impairments.
      Data from a re-analysis of an earlier epdemiological study of psychiatric
      disorder in deaf children and adolescents suggests that these disorders are
      commoner than expected in deaf children and share the features of ADHD and
      hyperkinetic disorder seen in hearing children.

PMID- 15579859
TI  - The relationships between reading processes and English skills of deaf college
      students.
AB  - This research project investigated the relationships between various working
      memory (WM) recoding processes and English language skills in a sample of 86
      prelingually deaf college students from varied educational backgrounds. Part 1
      reports the results of a short-term memory (STM) experiment and a Recoding
      Strategies questionnaire. The STM results suggested that, for most deaf students,
      neither the speech, sign, or visual codes are as efficient as the speech code of
      hearing persons for the purpose of maintaining English linguistic information in
      WM. However, the ability to use speech-based recoding processes was positively
      correlated with WM capacity, and the use of sign recoding was found to decrease
      as the ability to make efficient use of a speech recoding strategy increased. In
      addition, the questionnaire data suggested that neither the speech nor sign
      recoding systems provide the majority of students with a complete internal
      representation of English surface structure grammatical information in WM. There
      was no evidence that the use of sign language in education interfered with the
      ability to develop a speech recoding strategy, or that knowledge of American Sign
      Language (ASL) negatively influenced the acquisition of English skills. The
      overall pattern of results suggested that WM processes and recoding strategies
      may be influencing grammatical processes, and the acquisition of English skills,
      in distinctive ways.

PMID- 15579860
TI  - Teaching sign language to hearing children as a possible factor in cognitive
      enhancement.
AB  - We describe an educational experience designed to teach Italian Sign Language
      (LIS) to a group of hearing children. The hypothesis underlying this experience
      was that learning a visual-gestural language such as LIS may improve children's
      attentional abilities, visual discrimination, and spatial memory. To examine this
      hypothesis, we conducted two studies. The first involved an educational
      experience lasting two years with a group of hearing children attending a Sign
      Language class from first to second grade. The Raven PM 47 TEST was administered
      at the beginning and at the end of each school year to children attending the LIS
      classes and to a control group of children enrolled in the same school but not
      exposed to LIS. The second study involved an educational experience in first
      grade. The Raven PM 47 and Corsi's block tapping tests were administered at the
      beginning and at the end of the school year to the children attending the LIS
      classes, to children enrolled in the same school but at tending an English class,
      and to children not exposed to a second language. We found that in both studies
      the LIS group performed better than the other groups. These results suggest that
      learning a sign language may lead to a cognitive advancement in hearing children.

PMID- 15579861
TI  - Vibrotactile speech tracking support: cognitive prerequisites.
AB  - Fourteen postlingually hearing-impaired participants took part in an intervention
      study on the potential benefit of three types of tactile aids (i.e., the
      Tactilator, Minivib 3, and the Tactaid 7). Although training by means of
      computerized tracking had substantial effects on speech tracking rate, no
      differential effects of type of aid emerged. However, a cognitive test battery
      revealed that training efficacy is directly dependent on the cognitive
      prerequisites of the individual speechreader. The speed with which an individual
      can make phonological judgments (i.e., rhyme judgments) and visual word decoding
      from lipreading proved to be critical cognitive skills. We conclude that these
      skills must be further assessed and taken into account when
      rehabilitation/training programs are launched.

PMID- 15579862
TI  - Evaluation of a training program using visible speech in German schools for the
      deaf.
AB  - The present study provides insight into several technical and computer-aided
      procedures that can be used with deaf students to improve their speech. A visible
      speech device combined with a training program was developed and evaluated in six
      German schools for the deaf. The teachers were initially given special
      instructions about the work with their students in accordance with our technical
      and training concept. The students were able to build up a knowledge of visible
      patterns of spoken sounds, syllables, and words. They used this knowledge to
      recognize speech errors and to improve their pronunciation. Teachers' experiences
      were mostly positive. As they said, this device made their work much easier. The
      results show that visible speech can be used effectively; however, it has to be
      embedded in a training program that systematically builds up phonological
      knowledge and considers symbolic meanings from signed and written language.

PMID- 15579863
TI  - Consensus on early identification of hearing loss?
AB  - The National Institutes of Health Consensus Development Conference on Early
      Identification of Hearing Impairment was convened to address the advantages of
      early identification of hearing impairment and the consequences of late
      identification of hearing impairment, the issue of which children should be
      screened for hearing impairment and when, the advantages and disadvantages of
      current screening methods, the question of which model for hearing screening and
      follow-up is preferred, and future directions for research in diagnosis and
      management of hearing impairment in infants and young children. Among their
      findings, the panel concluded that (1) all infants admitted to the neonatal
      intensive care unit be screened for hearing loss prior to discharge, (2)
      universal screening be implemented for all infants within the first 3 months of
      life, (3) the preferred model for screening should begin with an evoked
      otoacoustic emissions test and should he followed by an auditory brainstem
      response test for all infants who fail the evoked otoacoustic emissions test, (4)
      comprehensive intervention and management programs must be an integral part of a
      universal screening program, (5) universal neonatal screening should not be a
      replacement for ongoing surveillance throughout infancy and early childhood, and
      (6) education of primary caregivers and primary health care providers on the
      early signs of hearing impairment is essential.

PMID- 15579864
TI  - Implicit phonological awareness and early reading development in prelingually
      deaf children.
AB  - This article reports on a longitudinal study of reading progress in a group of
      five-year-old deaf children and a group of hearing controls. All children were
      prereaders at the beginning of the study and the IQ of the two groups were
      matched. The deaf children varied considerably on a number of measures, including
      implicit phonological awareness, oral ability, and familiarity with British Sign
      Language and fingerspelling. Overall, the deaf children made significantly less
      reading progress than their hearing peers over the first year of schooling, and
      they also scored significantly lower on the test of rime and onset awareness.
      However, considerable variation in the reading progress of the deaf children was
      positively correlated with oral skills, rime/onset awareness, and language
      comprehension. Language comprehension, itself, was positively correlated with
      signing and fingerspelling. The deaf children were assessed again one year later,
      when learning to read continued to be very delayed, and the pattern of
      correlation was essentially the same. The implications of these findings for the
      education of deaf children are discussed.

PMID- 15579865
TI  - Using silent motion pictures to teach complex syntax to adult deaf readers.
AB  - This research tested whether silent motion pictures could be a source of contexts
      that fostered comprehension of relative clause and passive voice sentences during
      reading. These two syntactic structures are chronically difficult for some deaf
      readers. According to the instructional strategy, while subjects watched silent
      comedy stories, the video display intermittently focused attention on short
      segments of action and then called for a decision regarding which of two
      sentences printed in a workbook described the action segment. After this, a
      display on the video screen provided feedback on the accuracy of the decision. If
      successful here, this approach might be applied to other areas of competence in
      order to elevate the generally low level of reading performance by many deaf
      students. The study applied a single subject design in order to measure sentence
      comprehension accuracy before and following use of the materials. The
      computerized testing procedure also measured sentence reading time, an index of
      attention use. Thus, these data allowed an examination of whether any increases
      in comprehension were associated with slower, more laborious rates of reading.
      The instructional approach was an indirect one sharing multiple aspects of whole
      language methodology, and the sample included deaf subjects at a variety of
      reading ability levels. This permitted examination of whether an indirect
      instructional approach could be successful with readers demonstrating relatively
      low reading ability. The central research question of the study was the following
      'Can this instructional method be effective with deaf readers?'.

PMID- 15579866
TI  - Written language abilities in deaf Italians.
AB  - Written texts produced by 10 Italian deaf native signers in four different
      writing tasks were analyzed. Data analysis focused on linguistic and orthographic
      nonstandard forms. The written production of deaf subjects with deaf parents (DD)
      was compared to the written production in two control groups: a group of 10
      hearing subjects with deaf parents (HD) and a group of 10 subjects who have had
      no contact with deaf people or sign language (HH). The results duplicate findings
      from previous studies. Deaf subjects display a pattern of selective difficulty
      with Italian grammatical morphology, especially with free-standing function
      words. The four different writing tasks used in the present study yield results
      indicating that text type does influence our assessment of deaf writing
      abilities. A comparison of the texts written by deaf native signers with those of
      two hearing groups confirms the view that difficulties in the acquisition of
      written Italian are best explained by deafness itself, not by the influence of a
      previously acquired Sign Language, and that the specific difficulties with
      grammatical morphology displayed by our deaf subjects cannot be attributed solely
      to their limited experience with written Italian.

PMID- 15579867
TI  - The written language of deaf adolescents: patterns of performance.
AB  - A study was conducted of the written language skills of a representative sample
      of 69 adolescents with severe and profound hearing losses, using both a
      standardized language sample (TOWL-2) and a letter. The overall results confirmed
      the generally low levels of performance typically found in this population and
      the existence of a developmental plateau. Nevertheless, performance levels were
      not uniformly low. The sample scored relatively high on measures of orthographic
      conventions and on semantics, but considerably lower on use of grammar. While
      females scored higher than males, and students in Auditory/Oral (A/O) programs
      scored higher than those in Total Communication (TC) programs, the profile of
      scores did not vary by group. In general, the letter elicited higher levels of
      performance than the standardized sample, although the latter elicited more
      grammatically complex writing. Factor analysis indicated that the various
      measures derived from the two samples were associated more strongly by genre than
      by levels of language form.

PMID- 15579868
TI  - An alternate route for preparing deaf children for BiBi programs: the home
      language as L1 and cued speech for conveying traditionally spoken languages.
AB  - This article focuses on nonsigning hearing parents of deaf children who share the
      goals of bilingual-bicultural (BiBi) programs for their child, opt for their home
      language to be their deaf child's first language (L1), and have questions about
      communication options (e.g., oral methods, manually coded English [MCE] systems,
      or Cued Speech) for conveying that language. We present research findings related
      to the effectiveness of MCE systems and Cued Speech for conveying English and
      developing deaf children's reading abilities. We compare the cueing of English
      and the signing of MCE systems in terms of theoretical and practical advantages.
      Finally, we suggest research needs.

PMID- 15579869
TI  - A comparison of the vocal patterns of deaf and hearing mother-infant dyads during
      face-to-face interactions.
AB  - This study was part of a longitudinal investigation of the impact of deafness on
      the cognitive, social, and communicative development of infants. The current
      study reports analyses of the vocalizations of deaf and hearing infants and their
      Deaf or hearing mothers during normal face-to-face interactions when the infants
      were 9 months old. Results indicate essentially no differences in the amount of
      positive or negative vocalizations emitted by infants in any of the four groups
      observed. However, there is a heightened use of vocal games by hearing mothers
      interacting with deaf infants, indicating that these mothers are incorporating
      several additional sensory modalities into their vocal expressions. This is
      interpreted as one way in which parents make their vocal communication more
      salient and accessible to an infant with a hearing loss. Deaf mothers are also
      highly active and engaged with their infants, but have been found to rely more
      extensively on vigorous tactile contact rather than auditory input during these
      same interactions.

PMID- 15579870
TI  - Constructing simultaneous communication: the contributions of natural sign
      language.
AB  - This article examines simultaneous communication (SC) by analyzing the changes in
      productions of teachers who underwent a program specifically designed to address
      improvements in the signed modality by working with both English-based signing
      and American Sign Language (ASL). Based on theoretical concepts found in
      bilingualism, language contact situations, and conversational analysis, we focus
      on the process of constructing utterances by examining the teachers' spontaneous
      repair sequences as evidence of an active productive system. Two teachers
      received special instruction in SC that included both ASL and English-based
      signing systems as separate but equal systems. Videotapes of their use of SC,
      collected over four years, were analyzed for sign/speech ratio and repair
      sequences. Repairs were classified as repetitions, replacements, or
      synchronization. We found that the sign/speech ratio of both teachers increased
      over time. Examination of repair sequences showed that repetitions tended to
      occur in speech with the sign channel more completely encoded in the repair.
      Changes in speech tended to be accompanied by changes in sign. Errors in
      synchrony were relatively rare. We conclude that the simultaneous communication
      of both teachers was speech-driven, but error detection was largely sign-driven.
      The greater the automaticity of both languages, the more attention could be
      devoted to monitoring the coordination of the two modalities. The amount and
      quality of monitoring that actually occurred, however, were subject to individual
      differences.

PMID- 15579871
TI  - Fluency in American sign language.
AB  - I used two experimental designs to investigate the perception of fluency by
      native Deaf signers. In experiment 1, seven native signers described the signing
      ability of other native signers judged to have a wide range of signing ability.
      The judges provided numerical ratings and descriptions of signing skill. These
      positive and negative descriptions were used in experiment 2 to determine if the
      judgments were reliable, valid, and predictive of fluency. In this study a
      different group of five raters judged the same signing samples using 21 pairs of
      criteria gleaned from experiment 1. Between- and within-group analyses
      demonstrated that these criteria could be used to reliably judge and predict
      fluency. Rate of signing was not found to be a crucial criterion for fluency. I
      discuss implications for the types of sign models used with Deaf children and
      teaching of ASL to second language users.

PMID- 15579872
TI  - Deaf/hearing cultural identity paradigms: modification of the deaf identity
      development scale.
AB  - The Deaf Identity Development Scale (Glickman, 1993) was modified to include
      hearing individuals and examine how hearing and deaf adults identify themselves.
      Statistical analysis based on 244 deaf, hard-of-hearing, and hearing respondents
      revealed a significant interaction between hearing status of self and parents on
      the hearing, marginal, and immersion scales of the modified version but not on
      the bicultural scale. Codas are more marginalized, less immersed, and similarly
      'hearing' in comparison to deaf persons with deaf parents. Hard-of-hearing
      respondents with deaf parents endorse more hearing values and fewer deaf values
      in comparison to deaf counterparts and also appear to be more marginalized. There
      were no significant differences between deaf and hard-of-hearing individuals with
      hearing parents. Compared to hearing respondents with hearing parents, deaf
      counterparts were more marginalized, more 'hearing,' and equally 'deaf.' Strong
      professional affiliation with the deaf community resulted in scores that differed
      significantly from those for individuals not as strongly affiliated. We discuss
      implications for identity development.

PMID- 15579873
TI  - Bilingual-bicultural models of literacy education for deaf students: considering
      the claims.
AB  - As Carolyn Ewoldt (1996) points out '[M]uch has been written of late about the
      viability of a bilingual focus in deaf education.' While these writings are
      necessary to the ongoing pedagogical dialogue in the field, much of the rhetoric
      suffers because, rather than truly adopting a 'holistic perspective', arguments
      and positions focus only on selected aspects of the relevant theoretical and
      research information. If proponents of bilingual education for deaf children
      truly rely on 'research on the benefits of native sign language and from
      theoretical and research support coming from other disciplines' (Ewoldt, 1996, p.
      5) to support their claims, then these research and theoretical supports must be
      examined as comprehensively, and holistically, as possible. Weaving together only
      a few threads of theory and research does not create the fabric for a pedagogical
      position that can withstand close scrutiny and analysis.In this article, we will
      touch on some of the major claims made in explications of bilingual models of
      literacy education for deaf students (Baker, 1997; Livingston, 1997; Mashie,
      1995; Mason & Ewoldt, 1996). Our goal is to broaden the scope of the discussion
      on some of the major arguments and to encourage an expanded dialogue in this
      ongoing debate. It is not our aim to argue against the concept of bilingual
      education for deaf students nor to advocate the exclusion of native sign
      languages from the classroom. Rather, we support the concept of a bilingual
      education for deaf students with native sign languages playing a key role;
      however, we contend that the model as it is currently conceived requires further
      scrutiny and analysis.

PMID- 15579874
TI  - Vygotsky, sign language, and the education of deaf pupils.
AB  - This article considers the impact of Vygotsky on the education of deaf children
      in Russia and is a translation/adaptation of an article currently being published
      in Defektologiia. While Vygotsky perceived sign language as limited in some
      aspects nevertheless, he always considered that it had a role in education of
      deaf pupils. He believed that sign language should not be 'treated like an the
      enemy' and said that 'bilingualism of def people is an objective reality'.
      However, sign language was banned from Russian schools following a conference
      decision in 1938. The changing political climate in Russia has lead to the
      reevaluation of many aspects of life, including approaches to education, and to a
      reassessment of Vygotsky's ideas and an appreciation of their continuing
      relevance. Among other things, this has resulted in a reevaluation of the role of
      sign language for deaf pupils and an emerging interest in sign bilingualism.

PMID- 15579875
TI  - Learning styles of deaf college students and instructors' teaching emphases.
AB  - Six learning style dimensions of the Grasha-Riechmann Student Learning Style
      Scales (GRSLSS) were examined in this study with 100 deaf college students. In
      addition, six corresponding scales of teaching emphases were administered to the
      16 instructors of these students. Student mean scores were higher for the
      dependent, participative, collaborative, and independent dimensions than for the
      competitive and avoidant styles. The participative learning style correlated
      significantly with course achievement and course interest, which suggests that an
      emphasis on active learning may be desirable. For instructors, as with students,
      the mean scores for teaching emphases were found to be higher for the
      collaborative, dependent, participative, and independent dimensions. the similar
      patterns of results for students and teachers suggest a correspondence between
      the learning styles and the teaching emphases.

PMID- 15579876
TI  - Parent bonding in clinically depressed deaf and hard-of-hearing adults.
AB  - This study assessed the relationships between parent communication variables and
      the parent bonding factors of care and overprotection using a sample of 38 deaf
      and hard-of-hearing individuals connected with mental health services who had DSM
      III-R or DSM-IV diagnoses of depression-related disorders. The 22 therapists
      working with these individuals also contributed to data collection. Results based
      on revised depression (BDI-R) and parent bonding (PBI-R) questionnaires, together
      with background data from both clients and therapists, indicate that higher
      ratings of depression are associated with less perceived care by mother and
      greater perceived overprotection by both mother and father. Paternal care and
      overprotection were negatively correlated, as were maternal care and
      overprotection. In comparison to hard-of-hearing counterparts, deaf participants
      were less depressed and had more positive ratings of communication with their
      parents. The BDI-R scores positively and significantly correlated with coded
      severity of diagnosis. Due to the small sample size, findings are suggestive.
      Further study is warranted.

PMID- 15579877
TI  - Shaping at the point of utterance: an investigation of the composing processes of
      the deaf student writer.
AB  - All writers face the challenge of making meaning on a blank page. They struggle
      to make meaning for themselves and to communicate this meaning to the potential
      readers of their texts. Although, in this way, the <it>act</it> of writing can be
      perceived as a solitary endeavor, the <it>activity</it> of writing, as one aspect
      of literacy development, is embedded in a sociocultural framework and must be
      considered not only from the perspective of an individual's mental functioning
      but from the social context in which it exists. What follows is a preliminary
      report from a larger case study examining the composing processes of four deaf
      student writers. This broader study aspires to the goal of sociocultural
      research, which is to understand the relationship between human mental
      functioning, on one hand and cultural historical and institutional settings, on
      the other (Wertsch, 1995). From such a perspective, individual mental processes
      and sociocultural setting are understood in terms of this relationship, and human
      action is understood in the context of interrelated moments. I focus on one
      'moment' of the writing process that I will term, to borrow a phrase from Stephen
      Krashen (1977) and James Britton (1978), 'shaping at the point of utterance.' In
      other words, I will explore what deaf writers do as they face the 'challenge of
      the blank page.'

PMID- 15579878
TI  - Israeli mothers' expectations from early intervention with their preschool deaf
      children.
AB  - Family-oriented early intervention programs have become a common practice in deaf
      education and intervention. This trend requires the extensive investigation of
      parents' expectations about programs and professionals in order to enhance the
      efficacy of parent-professional collaboration. The goal of this study was to
      closely examine the expectations of mothers whose children were already enrolled
      i a comprehensive early intervention program for deaf children and their
      families. Three means of data collection were utilized: two open-ended written
      questions, an individual oral interview with the mother, and a set of formal
      questionnaires on various maternal, family, and child characteristics. A
      heterogeneous sample of 50 mothers of 2- to 5-year-old deaf children in Israel
      participated in the study. A wealth of maternal expectations emerged from this
      qualitative methodology, underscoring mothers' impressive knowledge and
      awareness, as well as individual differences. Through cluster analysis, the
      mothers were sorted into four distinct groups, yielding interesting patterns of
      expectations for programs and processionals.

PMID- 15579879
TI  - Antonio Provolo: hero or villain?
AB  - Antonio Provolo, of Verona Italy (1801-1842), was a priest who was 'inspired' to
      teach deaf children by giving them the gift of speech through music. Under the
      patronage of a wealthy noblewoman he set up a school in Verona where he taught
      'deafmutes' to peak with normal intonation and rhythm and to sing. He was a
      gifted musician himself and used his skills and training to develop his
      brilliantly innovative techniques, which are briefly described in this article.
      But, like many dedicated innovators, he was a fanatic. To further his system, he
      insisted on banning any use of sign-and thus indirectly contributed to the
      banning of sign at the Milan Conference in 1880.

PMID- 15579880
TI  - Health care delivery and deaf people: practice, problems, and recommendations for
      change.
AB  - Due to complex individual, interpersonal, and systemic factors, deaf and hard of
      hearing (d/hoh) individuals often receive inadequate, inappropriate, and
      unethical health care. This article begins with a review of the relevant
      socioeconomic and legal issues and the health status of d/hoh individuals. I then
      review health care starting with the patient's knowledge base, personal
      experiences, and understanding of health care relationships. I discuss the Deaf
      community's perspectives, providers' views about disability, communication
      between providers and deaf patients, and barriers encountered in health care
      delivery. The article concludes by assessing these factors' effects on health
      care delivery to d/hoh people, reviewing the ethical implications, and making
      recommendations for change.

PMID- 15579881
TI  - Deaf children's spelling: does it show sensitivity to phonology?
AB  - A written pictures to spelling task was given to two groups of children, 17 deaf
      children from signing schools (average age = 10.7) and 20 hearing children
      learning English as a second language (ESL, average age = 10.4). The stimuli were
      equally divided according to frequency, phonological regularity, and orthographic
      regularity. We predicted that the deaf group would not differ from the ESL group
      in the pattern of their responses across word classes, categorized in terms of
      the effect of frequency and phonological and orthographic regularity. Results
      showed that broadly this was the case, but more detailed analysis showed that the
      approach of the two groups was different. More specifically, the deaf children
      appeared to be sensitive to, but not aware of, phonology in their spelling,
      whereas the ESL group showed awareness of, as well as sensitivity to, phonology
      in their spelling.

PMID- 15579882
TI  - Do deaf children use phonological syllables as reading units?
AB  - This study aimed at examining whether deaf children process written words on the
      basis of phonological units. In French, the syllable is a phonologically and
      orthographically well-defined unit. French deaf children and hearing children
      matched on word recognition level were asked to copy written words and pseudo
      words. The number of glances at the item, copying duration, and the locus of the
      first segmentation (i.e., after the first glance) within the item were measured.
      The main question was whether the segments copied by the deaf children
      corresponded to syllables as defined by phonological and orthographic rules.The
      results showed that deaf children, like hearing children, used syllables as
      copying units when the syllable boundaries were marked both by orthographic and
      phonological criteria. However, in a condition in which orthographic and
      phonological criteria were differentiated, the deaf children did not perform
      phonological segmentations while the hearing children did. We discuss two
      explanatory hypotheses. First, items in this condition were difficult to decode
      for deaf children; second, orthographic units were probably easier to process for
      deaf children than phonological units because of a lack of automaticity in their
      phonological conversion processes for pseudo-words. Finally, incidental
      observations during the experimental task raised the question of the use of
      fingerspelled units.

PMID- 15579883
TI  - Skill levels of educational interpreters working in public schools.
AB  - The Educational Interpreter Performance Assessment, or EIPA, is an evaluation
      tool designed specifically for educational interpreters. An evaluation using the
      EIPA considers the child's grade level, the sign language or sign system that the
      interpreter is using as well as any other child-specific factors. Fifty-nine
      educational interpreters were evaluated using the EIPA. They had different
      backgrounds and training, and used different types of sign language or sign
      language or sign systems. The results show that not all of the educational
      interpreters were qualified to provide a child with an adequate interpretation of
      classroom discourse. Less than half of the educational interpreters assessed in
      this study performed at a level considered minimally acceptable. These data also
      show that sign vocabulary skills were significantly better than grammatical
      skills. Eighteen interpreters were evaluated twice in order to test-retest
      reliability, which showed that scores were not significantly different between
      the two evaluations. The picture that emerges from these data is that many deaf
      children receive an interpretation of classroom discourse that may distort and
      inadequately represent the information being communicated.

PMID- 15579884
TI  - Mixed deaf-hearing families: maximizing benefits and minimizing risks.
AB  - This article examines certain dynamics that may occur in families where the
      parent(s) and one or more children differ in hearing status (i.e., 'mixed deaf
      hearing families'). The essay has proved useful in promoting discussion during
      parenting workshops we have led. Hearing status differences between parents and
      children can be a cherished aspect of a family's diversity or a stage upon which
      family conflicts are acted out. We explore dynamics that lead to healthy versus
      unhealthy management of these hearing differences, especially as they relate to
      parental confidence, problem attribution, stages of child development, and
      information management.

PMID- 15579885
TI  - Considerations in educating deaf and hard-of-hearing students in inclusive
      settings.
AB  - This article provides an overview of key issues pertinent to an inclusive
      approach to the education of deaf students in order to establish a context for
      interpreting and integrating the articles in this issue. It discusses definitions
      of inclusion, integration, and mainstreaming from placement-related,
      philosophical, and pragmatic perspectives. The article provides demographic
      information pertinent to an inclusive approach. It also compares perspectives on
      inclusion in the general field of special education with those in the education
      of deaf and hard-of-hearing students. It considers the challenges of using an
      inclusive approach to achieve academic and social integration of students, as
      based on research on the learning and adjustment of deaf and hard-of-hearing
      students in regular classes. The article concludes with an overview of the topics
      addressed in the issue.

PMID- 15579886
TI  - Including the kids across the hall: collaborative instruction of hearing, deaf,
      and hard-of-hearing students.
AB  - This study follows graduate interns and their cooperating teachers through a
      collaborative student teaching experience in D/HH and hearing classrooms at the
      same grade level. Teacher teams, enrolled in a graduate course on collaboration,
      designed and conducted collaborative instruction (K-junior high school level),
      which focused on cooperative learning activities. Measures included student
      evaluations and separate intern and teacher evaluations of student performance,
      the integrated instructional units, and professional collaboration. Student
      evaluations included positive responses to integrated instruction by both groups,
      though there was more trepidation expressed by some D/HH students. Teachers
      reported very positive outcomes for all students including increased motivation
      to learn about and to interact with the other group and, for D/HH students, an
      increase in socially and academically appropriate behaviors. Specific student
      needs for training prior to integrated experiences were noted. Teachers stressed
      the importance of topic selections that would involve the expertise of all
      participants equally, needs for teacher in-service training and, administrative
      support for collaborative planning.

PMID- 15579887
TI  - Participation of deaf and hard-of-hearing students in classes with hearing
      students.
AB  - This project identified key issues concerning participation of deaf and hard-of
      hearing (D/HH) students in regular (mainstream) classes. In one study,
      qualitative data were collected from 40 participants in focus groups consisting
      of interpreters, teachers of the deaf, and notetakers. In a second study,
      repeated field observations were made of four elementary-level D/HH students who
      were participating in small-group learning activities with hearing classmates.
      Focus group comments indicated that regular classroom teachers, interpreters,
      teachers of the deaf, hearing classmates, and D/HH students contribute to active
      participation by the D/HH student. Focus groups identified specific barriers that
      interfered with participation of each of these groups of individuals, and they
      also identified specific strategies to facilitate participation. Qualitative
      analyses of field observation data yielded results consistent with the comments
      collected from the focus groups participants. The observations identified
      accommodations that regular classroom teachers, teachers of the deaf, and
      interpreters can make to promote integration of the D/HH student. A summary
      synthesis of the data presents 16 specific strategies for overcoming barriers to
      participation.

PMID- 15579888
TI  - The roles of special educators and classroom teachers in an inclusive school.
AB  - The research examined one school's attempts to include and integrate deaf and
      hard-of-hearing children. Interviews with teachers and observations of classrooms
      over a 3-year period revealed the critical roles played by the special educators
      and the classroom teachers. The responsibilities of the special educators, the
      adaptations and accommodation made by the classroom teachers, issues regarding
      ownership and attitude of the classroom teachers, perceptions of the special
      educator role, and specific areas of concern expressed by the special educators
      and classroom teachers are described.

PMID- 15579889
TI  - Team-teaching in an integrated classroom: perceptions of deaf and hearing
      teachers.
AB  - This study examined the perceptions of teams of two teachers, one deaf and one
      hearing, team-teaching students who are deaf and hard-of-hearing (D/HH) in co
      enrolled classrooms. Five teachers who had worked in teams and their supervisor
      were interviewed about their team-teaching experiences and their perception of
      the effectiveness of this approach. Informants' responses were videotaped,
      transcribed, and analyzed. From the interview data, four main categories were
      identified: (1) philosophy of education, (2) perception of roles, (3) benefits of
      team-teaching, and (4) challenges. Findings revealed that team-teaching in co
      enrolled classrooms gave all students access to their own and each other's
      cultures, languages, and social identities; deaf and hearing people were seen to
      have equality of status and students who are D/HH were seen to benefit from
      teachers' high expectations.

PMID- 15579890
TI  - Inclusive instruction and learning for deaf students in postsecondary education.
AB  - This article explores how students who are deaf and their instructors experience
      mainstream college classes. Both quantitative and qualitative procedures were
      used to examine student access to information and their sense of belonging and
      engagement in learning. Instructors were asked to discuss their approach to
      teaching and any instructional modifications made to address the needs of deaf
      learners. Results indicate that deaf students viewed classroom communication and
      engagement in a similar manner as their hearing peers. Deaf students were more
      concerned about the pace of instruction and did not feel as much a part of the
      'university family' as did their hearing peers. Faculty generally indicated that
      they made few if any modifications for deaf students and saw support service
      faculty as responsible for the success or failure of these students. We discuss
      results of these and additional findings with regard to barriers to equal access
      and strategies for overcoming these barriers.

PMID- 15579891
TI  - Inclusive education and personal development.
AB  - Open-ended questionnaires covering mainstream educational experiences and
      personal development of deaf and hard-of-hearing adults were analyzed. Half of
      the 34 deaf and hard-of-hearing respondents altered self-labels based on changes
      in personal definitions rather than audiological changes. Supportive school
      environments and coping skills contributed to positive perceptions; nonsupportive
      school environments and being treated as 'different' were viewed negatively.
      Everyone valued contact with hearing peers. Contact with deaf peers depended on
      finding those with similar values. Identification with Deaf culture was
      nonexistent. Most noteworthy, 24 of 34 participants felt caught between the deaf
      and hearing worlds, indicating the need for niches in both. Implications for
      educators are that development of self-confidence and comfort with identity may
      be enhanced by validating the deafness dimension through opportunities for
      contact with deaf adults and positive relationships with both deaf and hearing
      peers.

PMID- 15579892
TI  - Some conclusions on the education of deaf and hard-of-hearing students in
      inclusive settings.

PMID- 15579893
TI  - The development and psychometric properties of the American sign language
      proficiency assessment (ASL-PA).
AB  - We describe the procedures for constructing an instrument designed to evaluate
      children's proficiency in American Sign Language (ASL). The American Sign
      Language Proficiency Assessment (ASL-PA) is a much-needed tool that potentially
      could be used by researchers, language specialists, and qualified school
      personnel. A half-hour ASL sample is collected on video from a target child
      (between ages 6 and 12) across three separate discourse settings and is later
      analyzed and scored by an assessor who is highly proficient in ASL. After the
      child's language sample is scored, he or she can be assigned an ASL proficiency
      rating of Level 1, 2, or 3. At this phase in its development, substantial
      evidence of reliability and validity has been obtained for the ASL-PA using a
      sample of 80 profoundly deaf children (ages 6-12) of varying ASL skill levels.
      The article first explains the item development and administration of the ASL-PA
      instrument, then describes the empirical item analysis, standard setting
      procedures, and evidence of reliability and validity. The ASL-PA is a promising
      instrument for assessing elementary school-age children's ASL proficiency. Plans
      for further development are also discussed.

PMID- 15579894
TI  - Adjunct aids in instructional prose: a multimedia study with deaf college
      students.
AB  - A computer-based science lesson was administered to 144 deaf college students
      grouped into low, middle, and high reading ability levels. Five instructional
      conditions were compared: (1) text only, (2) text and content movies, (3) text
      and sign movies, (4) text and adjunct questions, and (5) all of these together
      (full condition). The low reading level subjects in the adjunct question and full
      conditions demonstrated immediate, factual learning performance comparable to
      that of the high reading level subjects in the text-only condition. These and
      other results of this investigation suggest the compensatory potential of adjunct
      aids and associated mathemagenic activities to improve factual learning from
      instructional prose for low reading ability students.

PMID- 15579895
TI  - Solving story-based arithmetic problems: achievement of children with hearing
      impairment and their interpretation of meaning.
AB  - This article considers how a sample of Norwegian school children, ages 6 through
      10 with hearing impairment, master three different types of elementary arithmetic
      problems presented in a nonreading format. The article outlines the effect of
      task-specific factors on the level of difficulty, as well as the children's
      understanding of problem structures. The results showed that semantic structure
      of the problems affected the level of difficulty. The problems were not solved
      significantly better by students from grade 4 than students from grade 1.
      Qualitative analyses revealed that the children interpreted the meaning of the
      imposed problems in three different ways: (1) as numbers and procedures, (2) as
      take-away situations, and (3) as part-part-whole relations.

PMID- 15579896
TI  - Maternal sensitivity predicts language gain in preschool children who are deaf
      and hard of hearing.
AB  - The link between maternal sensitivity and child language gain was assessed in a
      prospective study of hearing mothers and their deaf and hard-of-hearing (D/HH)
      children. Maternal sensitivity in dyadic interaction was assessed when children
      were approximately 2 years old, and expressive language gain was assessed at 2 to
      3 years using the Minnesota Child Development Inventory. Sensitivity made
      significant, positive, and unique predictions of expressive language gain when
      the effects of maternal education, degree of child hearing loss, dyadic mode of
      communication, and time between assessments were controlled. Findings indicate
      the value of affective measures of interaction in predicting language gain.

PMID- 15579897
TI  - Interpersonal communication skills of deaf adolescents and their relationship to
      communication history.
AB  - As part of a longitudinal study, the conversational skills of 67 deaf adolescents
      were assessed in spoken English, simultaneous communication (SimCom) and American
      Sign Language (ASL). Two groups of students were identified on the basis of the
      communication used in their current educational program: a small group of 16
      students in programs using spoken English (oral) and a larger group of 51
      students in programs using sign communication (bimodal). Students in spoken
      English programs had good spoken English skills and limited ASL skills, whereas
      the reverse was true for students in bimodal programs. Most students demonstrated
      sufficient skill in one or more systems to meet basic interpersonal
      communications needs, but not those required for advanced academic discourse. In
      neither group was spoken English related to ASL skill. SimCom skills were
      strongly related to spoken English in the oral program group and to ASL in the
      bimodal program group. Spoken English in adolescence was highly predictable from
      spoken English in early childhood. Within the bimodal program group, students
      with deaf parents had better SimCom and ASL skills than those with hearing
      parents. Among bimodal program students with hearing parents, better SimCom
      skills (but not ASL skills) were associated with earlier introduction to sign
      communication in school and to mothers' use of sign communication.

PMID- 15579898
TI  - A treatise from enlightenment Sweden on 'teaching the mute to read and speak'.
AB  - This note introduces the earliest Swedish treatise on the education of the deaf.
      It arose in the unlikely circumstances of a manse and the residence of the
      director of a saltpeter boilery in a small town in eighteenth-century Finland.
      Its interest today is in its distant reflection of the pedagogical trials (and
      errors) then taking place in Enlightenment Europe and in its combination of
      humanity, respect for signing, and goals of intelligible speech and literacy.

PMID- 15579899
TI  - Structure and regulation of the murine reduced folate carrier gene:
      identification of four noncoding exons and promoters and regulation by dietary
      folates.
AB  - The upstream structure and regulation of the mouse reduced folate carrier (mRFC)
      gene was characterized. By 5'-rapid amplification of cDNA ends assay and DNA
      sequencing from mouse tissues and 7-15-day stage embryos, mRFC transcripts with
      four unique 5' noncoding exons, designated mRFC-a,-b,-c, and -d, were identified
      mapping over 6300 bp. The 5' noncoding exons were characterized by multiple
      transcription starts and, for form b, two alternate splice forms. mRFC transcript
      forms were measured by real-time reverse transcription-PCR in mouse tissues and
      embryos and in L1210 leukemia and BNL CL.2 liver cell lines. The highest mRFC
      levels were detected in kidney and brain. mRFC-b and -c were the major transcript
      forms, with low levels of mRFC-a and -d. The 5'-flanking regions for exons a-d
      each exhibited promoter activity in reporter gene assays. mRFC transcripts and
      individual noncoding exons were measured in small intestine and kidney from mice
      fed folate-deficient or -replete diets. Mice fed the folate-deficient diet
      exhibited a significant (13.8-fold) increase in total mRFC transcripts and
      protein in the small intestine, reflecting increases in each of the mRFC-b, -c,
      and -d forms. Only minor changes in mRFC transcript levels or distributions were
      detected for kidney. Levels of folate-binding protein alpha were also increased
      in both small intestine and kidney in folate-deficient mice (91- and 2-fold,
      respectively). Multidrug resistance-associated proteins 1 and 3 were, likewise,
      elevated in intestine from folate-deficient mice (53- and 168-fold,
      respectively); however, there were no significant changes in kidney. Our results
      document the existence of four unique noncoding exons and promoters for mRFC and
      demonstrate a facile induction of mRNAs for mRFC and multidrug resistance
      associated proteins 1 and 3 in intestine in response to changes in dietary folate
      intake.

PMID- 15579900
TI  - Involvement of toll-like receptor 3 in the immune response of lung epithelial
      cells to double-stranded RNA and influenza A virus.
AB  - Influenza A is a highly contagious single-stranded RNA virus that infects both
      the upper and lower respiratory tracts of humans. The host innate immune Toll
      like receptor (TLR) 3 was shown previously in cells of myeloid origin to
      recognize the viral replicative, intermediate double-stranded RNA (dsRNA). Thus,
      dsRNA may be critical for the outcome of the infection. Here we first compared
      the activation triggered by either influenza A virus or dsRNA in pulmonary
      epithelial cells. We established that TLR3 is constitutively expressed in human
      alveolar and bronchial epithelial cells, and we describe its intracellular
      localization. Expression of TLR3 was positively regulated by the influenza A
      virus and by dsRNA but not by other inflammatory mediators, including bacterial
      lipopolysaccharide, the cytokines tumor necrosis factor-alpha and interleukin
      (IL)-1beta, and the protein kinase C activator phorbol 12-myristate 13-acetate.
      We also demonstrated that TLR3 contributes directly to the immune response of
      respiratory epithelial cells to influenza A virus and dsRNA, and we propose a
      molecular mechanism by which these stimuli induce epithelial cell activation.
      This model involves mitogen-activated protein kinases, phosphatidylinositol 3
      kinase/Akt signaling, and the TLR3-associated adaptor molecule TRIF but not MyD88
      dependent activation of the transcription factors NF-kappaB or interferon
      regulatory factor/interferon-sensitive response-element pathways. Ultimately,
      this signal transduction elicits an epithelial response that includes the
      secretion of the cytokines IL-8, IL-6, RANTES (regulated on activation normal T
      cell expressed and secreted), and interferon-beta and the up-regulation of the
      major adhesion molecule ICAM-1.

PMID- 15579901
TI  - Magnesium regulates ADP dissociation from myosin V.
AB  - Processivity in myosin V is mediated through the mechanical strain that results
      when both heads bind strongly to an actin filament, and this strain regulates the
      timing of ADP release. However, what is not known is which steps that lead to ADP
      release are affected by this mechanical strain. Answering this question will
      require determining which of the several potential pathways myosin V takes in the
      process of ADP release and how actin influences the kinetics of these pathways.
      We have addressed this issue by examining how magnesium regulates the kinetics of
      ADP release from myosin V and actomyosin V. Our data support a model in which
      actin accelerates the release of ADP from myosin V by reducing the magnesium
      affinity of a myosin V-MgADP intermediate. This is likely a consequence of the
      structural changes that actin induces in myosin to release phosphate. This effect
      on magnesium affinity provides a plausible explanation for how mechanical strain
      can alter this actin-induced acceleration. For actomyosin V, magnesium release
      follows phosphate release and precedes ADP release. Increasing magnesium
      concentration to within the physiological range would thus slow both the ATPase
      activity and the velocity of movement of this motor.

PMID- 15579902
TI  - Isolation of a gene encoding a 1,2-diacylglycerol-sn-acetyl-CoA acetyltransferase
      from developing seeds of Euonymus alatus.
AB  - 1,2-Diacyl-3-acetyl-sn-glycerols (ac-TAG) are unusual triacylglycerols that
      constitute the major storage lipid in the seeds of Euonymus alatus (Burning
      Bush). These ac-TAGs have long-chain acyl groups esterified at both the sn-1 and
      sn-2 positions of glycerol. Cell-free extracts of developing seeds of E. alatus
      contain both long-chain acyl-CoA and acetyl-CoA sn-1,2-diacylglycerol
      acyltransferase (DGAT) activity. We have isolated a gene from developing seeds of
      Euonymus alatus that shows a very high sequence similarity to the members of the
      DGAT1 gene family (i.e. related to acyl-CoA:cholesterol acyltransferases). This
      Euonymus DGAT1 gene, when expressed in wild type yeast, results in a 5-fold
      enhancement of long-chain triacylglycerol (lc-TAG) accumulation, as well as the
      appearance of low levels of ac-TAG. Hydrogenated ac-TAG molecular species were
      identified by gas chromatography-mass spectrometry. Microsomes isolated from this
      transformed yeast show diacylglycerol:acetyl-CoA acetyltransferase activity,
      which is about 40-fold higher than that measured in microsomes prepared from
      yeast transformed with the empty vector or with the Arabidopsis thaliana DGAT1
      gene. The specific activity of this microsomal acetyltransferase activity is of
      the same order of magnitude as the microsomal long-chain DGAT activities measured
      for yeast lines transformed with the empty vector or either the Arabidopsis or
      Euonymus DGAT1 genes. Despite this, ac-TAG accumulation in yeast transformed with
      the Euonymus DGAT1 gene was very low (0.26% of lc-TAG), whereas lc-TAG
      accumulation was enhanced. Possible reasons for this anomaly are discussed.
      Expression of the Euonymus DGAT1-like gene in yeast lines where endogenous TAG
      synthesis has been deleted confirmed that the gene product has both long-chain
      acyl- and acetyltransferase activity.

PMID- 15579903
TI  - Changes in Mg2+ ion concentration and heavy chain phosphorylation regulate the
      motor activity of a class I myosin.
AB  - Class I myosins are single-headed motor proteins implicated in various motile
      processes including organelle translocation, ion channel gating, and cytoskeleton
      reorganization. Dictyostelium discoideum myosin-ID belongs to subclass 1alpha,
      whose members are thought to be tuned for rapid sliding. The direct analysis of
      myosin-ID motor activity is made possible by the production of single polypeptide
      constructs carrying an artificial lever arm. Using these constructs, we show that
      the motor activity of myosin-ID is activated 80-fold by phosphorylation at the
      TEDS site. TEDS site phosphorylation acts by stabilizing the actomyosin complex
      and increasing the coupling between actin binding and the release of hydrolysis
      products. A surprising effect of Mg(2+) ions on in vitro motility was discovered.
      Changes in the level of free Mg(2+) ions within the physiological range are shown
      to modulate motor activity by inhibiting ADP release. Our results indicate that
      higher concentrations of free Mg(2+) ions stabilize the tension-bearing actin
      myosin ADP state and shift the system from the production of rapid movement
      toward the generation of tension.

PMID- 15579904
TI  - Integrin alpha6beta4-erbB2 complex inhibits haptotaxis by up-regulating E
      cadherin cell-cell junctions in keratinocytes.
AB  - Keratinocyte integrins alpha6beta4 and alpha3beta1 bind laminin-5, a component of
      basement membranes. We previously demonstrated that in keratinocytes, haptotactic
      migration on laminin-5 was stimulated by anti-beta1 integrin-activating antibody
      TS2/16, whereas antibodies to alpha6 and beta4, respectively, blocked TS2/16
      induced, alpha3beta1-dependent migration. Moreover, alpha6beta4-associated
      haptotaxis inhibition was linked to a phosphatidylinositol 3-kinase (PI3K)
      pathway and required erbB2 activation. erbB2, the ligand-less member of the
      epidermal growth factor receptor family, was shown to form a complex with the
      hemidesmosomal integrin alpha6beta4. Here, we demonstrate that alpha6beta4
      inhibitory effects on haptotaxis are abolished by an anti-E-cadherin antibody,
      which interferes with cell-cell adhesion. Furthermore, antibodies to alpha6 and
      beta4 stimulated adhesion to an E-cadherin-Fc recombinant protein. In addition,
      anti-alpha6/beta4 antibodies increased colony size in plated cells, stimulated
      cell-cell aggregation, and up-regulated E-cadherin localization to cell-cell
      contacts. These effects were abolished when erbB2 or PI3K were blocked. These
      results indicate that stimulation of alpha6beta4 increases E-cadherin-mediated
      cell-cell adhesion and that this mechanism depends on erbB2 activation. The
      molecule that links alpha6beta4 with E-cadherin may be the small GTPase cdc42, an
      effector of PI3K, because dominant-negative cdc42 abolished the inhibitory effect
      of anti-alpha6/beta4 antibodies and increased basal migration, whereas
      constitutively active cdc42 prevented the TS2/16-induced increase in haptotaxis.
      These findings suggest a model whereby alpha6beta4 can augment cell-cell adhesion
      and slow down haptotaxis over laminin-5 and point to the alpha6beta4-erbB2
      heterodimer as an important signaling complex for the formation of cohesive
      keratinocyte layers.

PMID- 15579905
TI  - Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA
      secondary structure.
AB  - Flap endonuclease 1 (FEN1) participates in removal of RNA primers of Okazaki
      fragments, several DNA repair pathways, and genome stability maintenance. Defects
      in yeast FEN1 produce chromosomal instability, hyper-recombination, and sequence
      duplication. These occur because flaps produced during replication are not
      promptly removed. Long-lived flaps sustain breaks and form misaligned bubble
      structures that produce duplications. Flaps that can form secondary structure
      inhibit even wild-type FEN1 and are more likely to form bubbles. Although
      proliferating cell nuclear antigen stimulates FEN1, it cannot resolve secondary
      structures. Bloom protein (BLM) is a 3'-5' helicase, mutated in Bloom syndrome.
      BLM has been reported to interact with and stimulate FEN1 independent of helicase
      function. We found activation of the helicase by ATP did not alter BLM
      stimulation of cleavage of unstructured flaps. However, BLM stimulation of FEN1
      cleavage of foldback flaps, bubbles, or triplet repeats was increased by an
      additional increment when ATP was added. Helicase-dependent stimulation of FEN1
      cleavage was robust over a range of sizes of the single-stranded part of bubbles.
      However, increasing the length of the 5' annealed region of the bubble ultimately
      counteracted the stimulatory capacity of the BLM helicase. Moderate helicase
      dependent stimulation was observed with both fixed and equilibrating CTG flaps.
      Our results suggest that BLM suppresses genome instability by aiding FEN1
      cleavage of structure-containing flaps.

PMID- 15579906
TI  - Cysteine-scanning mutagenesis of muscle carnitine palmitoyltransferase I reveals
      a single cysteine residue (Cys-305) is important for catalysis.
AB  - Carnitine palmitoyltransferase (CPT) I catalyzes the conversion of long-chain
      fatty acyl-CoAs to acyl carnitines in the presence of l-carnitine, a rate
      limiting step in the transport of long-chain fatty acids from the cytoplasm to
      the mitochondrial matrix. To determine the role of the 15 cysteine residues in
      the heart/skeletal muscle isoform of CPTI (M-CPTI) on catalytic activity and
      malonyl-CoA sensitivity, we constructed a 6-residue N-terminal, a 9-residue C
      terminal, and a 15-residue cysteineless M-CPTI by cysteine-scanning mutagenesis.
      Both the 9-residue C-terminal mutant enzyme and the complete 15-residue
      cysteineless mutant enzyme are inactive but that the 6-residue N-terminal
      cysteineless mutant enzyme had activity and malonyl-CoA sensitivity similar to
      those of wild-type M-CPTI. Mutation of each of the 9 C-terminal cysteines to
      alanine or serine identified a single residue, Cys-305, to be important for
      catalysis. Substitution of Cys-305 with Ala in the wild-type enzyme inactivated M
      CPTI, and a single change of Ala-305 to Cys in the 9-residue C-terminal
      cysteineless mutant resulted in an 8-residue C-terminal cysteineless mutant
      enzyme that had activity and malonyl-CoA sensitivity similar to those of the wild
      type, suggesting that Cys-305 is the residue involved in catalysis. Sequence
      alignments of CPTI with the acyltransferase family of enzymes in the GenBank led
      to the identification of a putative catalytic triad in CPTI consisting of
      residues Cys-305, Asp-454, and His-473. Based on the mutagenesis and substrate
      labeling studies, we propose a mechanism for the acyltransferase activity of CPTI
      that uses a catalytic triad composed of Cys-305, His-473, and Asp-454 with Cys
      305 serving as a probable nucleophile, thus acting as a site for covalent
      attachment of the acyl molecule and formation of a stable acyl-enzyme
      intermediate. This would in turn allow carnitine to act as a second nucleophile
      and complete the acyl transfer reaction.

PMID- 15579907
TI  - VE-cadherin links tRNA synthetase cytokine to anti-angiogenic function.
AB  - A natural fragment of an enzyme that catalyzes the first step of protein
      synthesis-human tryptophanyl-tRNA synthetase (T2-TrpRS) has potent anti
      angiogenic activity. A cellular receptor through which T2-TrpRS exerts its anti
      angiogenic activity has not previously been identified. Here T2-TrpRS was shown
      to bind at intercellular junctions of endothelial cells (ECs). Using genetic
      knock-outs, binding was established to depend on VE-cadherin, a calcium-dependent
      adhesion molecule, which is selectively expressed in ECs, concentrated at
      adherens junctions, and is essential for normal vascular development. In
      contrast, T2-TrpRS binding to EC junctions was not dependent on platelet
      endothelial cell adhesion molecule type-1, another adhesion molecule found at EC
      junctions. Pull-down assays confirmed direct complex formation between T2-TrpRS
      and VE-cadherin. Binding of T2-TrpRS inhibited VEGF-induced ERK activation and EC
      migration. Thus, a VE-cadherin-dependent pathway is proposed to link T2-TrpRS to
      inhibition of new blood vessel formation.

PMID- 15579908
TI  - A neural Wiskott-Aldrich Syndrome protein-mediated pathway for localized
      activation of actin polymerization that is regulated by cortactin.
AB  - Activation of the epidermal growth factor (EGF) receptor can stimulate actin
      polymerization via the Arp2/3 complex using a number of signaling pathways, and
      specific stimulation conditions may control which pathways are activated. We have
      previously shown that localized stimulation of EGF receptor with EGF bound to
      beads results in localized actin polymerization and protrusion. Here we show that
      the actin polymerization is dependent upon activation of the Arp2/3 complex by
      neural Wiskott-Aldrich Syndrome protein (N-WASP) via Grb2 and Nck2. Suppression
      of Grb2 or Nck2 results in loss of localization of N-WASP at the activation site
      and reduced actin polymerization. Although cortactin has been found to synergize
      with N-WASP for Arp2/3-dependent actin polymerization in vitro, we find that
      cortactin can restrict N-WASP localization around EGF-bead-induced protrusions.
      In addition, cortactin-deficient cells have increased lamellipod dynamics but
      show reduced net translocation, suggesting that cortactin can contribute to cell
      polarity by controlling the extent of Arp2/3 activation by WASP family members
      and the stability of the F-actin network.

PMID- 15579909
TI  - Axin contains three separable domains that confer intramolecular, homodimeric,
      and heterodimeric interactions involved in distinct functions.
AB  - Axin is a major scaffold protein, interacting with diverse molecules involved in
      a number of signaling pathways. Axin can undergo dimer/oligomerization via its
      DIX domain. Here we show that whereas deletion of the DIX domain at the C
      terminus rendered Axin incapable of forming dimer, a larger deletion of the C
      terminal region restored the ability of Axin to form dimers. Detailed analyses
      revealed that Axin actually contains two separate domains (D and I) in addition
      to the DIX domain for homodimerization. The D, I, and DIX domains alone can form
      homodimers. Interestingly, D and I domains strongly interact with each other,
      suggesting that Axin can form an intramolecular structure through D and I
      interaction in the absence of DIX. We also found that DIX-DIX homodimeric
      interaction is weak but that point mutations in the DIX domain abolished Axin
      homodimerization. We propose a model to suggest that Axin forms homodimeric
      interactions through three domains, D, I, and DIX. More importantly, lack of DIX
      DIX interaction caused by point mutations in the DIX domain or deletion causes
      Axin to form an intramolecular loop through the D and I domains, disallowing
      homodimer formation. Ccd1 interacts with Axin D domain yet fails to interact with
      AxinDeltaDIX, confirming that D is masked after D-I looping. The Axin mutants
      that are defective in homodimer formation fail to activate JNK but have no effect
      on beta-catenin signaling. Our findings have thus provided a structural basis of
      conformational changes in Axin, which may underlie the diversity of Axin
      functions.

PMID- 15579910
TI  - Pleckstrin homology domains of phospholipase C-gamma1 directly interact with beta
      tubulin for activation of phospholipase C-gamma1 and reciprocal modulation of
      beta-tubulin function in microtubule assembly.
AB  - Phosphoinositide-specific phospholipase C-gamma1 (PLC-gamma1) has two pleckstrin
      homology (PH) domains, an N-terminal domain and a split PH domain. Here we show
      that pull down of NIH3T3 cell extracts with PLC-gamma1 PH domain-glutathione S
      transferase fusion proteins, followed by matrix-assisted laser desorption
      ionization-time of flight-mass spectrometry, identified beta-tubulin as a binding
      protein of both PLC-gamma1 PH domains. Tubulin is a main component of
      microtubules and mitotic spindle fibers, which are composed of alpha- and beta
      tubulin heterodimers in all eukaryotic cells. PLC-gamma1 and beta-tubulin
      colocalized in the perinuclear region in COS-7 cells and cotranslocated to the
      plasma membrane upon agonist stimulation. Membrane-targeted translocation of
      depolymerized tubulin by agonist stimulation was also supported by
      immunoprecipitation analyses. The phosphatidylinositol 4,5-bisphosphate (PIP(2))
      hydrolyzing activity of PLC-gamma1 was substantially increased in the presence of
      purified tubulin in vitro, whereas the activity was not promoted by bovine serum
      albumin, suggesting that beta-tubulin activates PLC-gamma1. Furthermore, indirect
      immunofluorescent microscopy showed that PLC-gamma1 was highly concentrated in
      mitotic spindle fibers, suggesting that PLC-gamma1 is involved in spindle fiber
      formation. The effect of PLC-gamma1 in microtubule formation was assessed by
      overexpression and silencing PLC-gamma1 in COS-7 cells, which resulted in altered
      microtubule dynamics in vivo. Cells overexpressing PLC-gamma1 showed higher
      microtubule densities than controls, whereas PLC-gamma1 silencing with small
      interfering RNAs led to decreased microtubule network densities as compared with
      control cells. Taken together, our results suggest that PLC-gamma1 and beta
      tubulin transmodulate each other, i.e. that PLC-gamma1 modulates microtubule
      assembly by beta-tubulin, and beta-tubulin promotes PLC-gamma1 activity.

PMID- 15579911
TI  - Vinculin controls PTEN protein level by maintaining the interaction of the
      adherens junction protein beta-catenin with the scaffolding protein MAGI-2.
AB  - PTEN is a frequently mutated tumor suppressor in malignancies. Interestingly,
      some malignancies exhibit undetectable PTEN protein without mutations or loss of
      PTEN mRNA. The cause(s) for this reduction in PTEN is unknown. Cancer cells
      frequently exhibit loss of cadherin, beta-catenin, alpha-catenin and/or vinculin,
      key elements of adherens junctions. Here we show that F9 vinculin-null (vin(-/-))
      cells lack PTEN protein despite normal PTEN mRNA levels. Their PTEN protein
      expression was restored by transfection with vinculin or by inhibition of PTEN
      degradation. F9 vin(-/-) cells express PTEN protein upon transfection with a
      vinculin fragment (amino acids 243-1066) that is capable of interacting with
      alpha-catenin but unable to target into focal adhesions. On the other hand,
      disruption of adherens junctions with an E-cadherin blocking antibody reduced
      PTEN protein to undetectable levels in wild-type F9 cells. PTEN protein levels
      were restored in F9 vin(-/-) cells upon transfection with an E-cadherin-alpha
      catenin fusion protein, which targets into adherens junctions and interacts with
      beta-catenin in F9 vin(-/-) cells. beta-Catenin is known to interact with MAGI-2.
      MAGI-2 interaction with PTEN in the cell membrane is known to prevent PTEN
      protein degradation. Thus, MAGI-2 overexpression in F9 vin(-/-) cells restored
      PTEN protein levels. Moreover, expression of vinculin mutants that reinstated the
      disrupted interactions of beta-catenin with MAGI-2 in F9 vin(-/-) cells also
      restored PTEN protein levels. These studies indicate that PTEN protein levels are
      dependent on the maintenance of beta-catenin-MAGI-2 interaction, in which
      vinculin plays a critical role.

PMID- 15579912
TI  - Monoclonal antibodies in the treatment of chronic lymphocytic leukemia.
AB  - Traditional therapy for chronic lymphocytic leukemia (CLL) has consisted of
      alkylating agents, purine analogs, or a combination of these drugs. These agents
      are effective at producing remissions but are not curative.Thus, new drugs are
      still needed to improve the outcome of patients with CLL. The introduction of
      monoclonal antibodies, such as rituximab and alemtuzumab, provides a novel
      therapeutic modality.Rituximab is an active agent in CLL. Standard doses of
      rituximab result in higher response rates in previously untreated than in
      relapsed patients but low complete response (CR) rates. Rituximab is most
      effective in combination with chemotherapy, especially fludarabine-based regimens
      in the first-line and salvage setting. Rituximab is also useful in the treatment
      of complications of CLL, such as pure red cell aplasia, autoimmune
      thrombocytopenia, and autoimmune hemolytic anemia. Alemtuzumab has impressive
      activity in patients with refractory CLL and may play an important role in the
      consolidation treatment of CLL. Alemtuzumab is most efficacious at clearing
      disease in the peripheral blood and bone marrow. Bulky lymphadenopathy is less
      sensitive to therapy. Because of the significant lymphopenia associated with
      alemtuzumab, antibacterial and antiviral prophylaxis should always be used.

PMID- 15579913
TI  - Two- vs three-drug combination chemotherapy in advanced or recurrent head and
      neck cancer: a single institution experience of 361 patients.
AB  - Head and neck squamous cancer is a major concern in India. The proportion of
      advanced cases is significantly high, and these patients have dismal survival
      prospects despite aggressive therapy. Often surgical resection and/or
      radiotherapy are not feasible in these patients. Hence, we decided to explore the
      option of neoadjuvant chemotherapy using effective agents like ifosfamide and
      paclitaxel in combination with cisplatin in these patients. A total of 361
      patients were evaluable at the end of study. Of these, 207 had received
      ifosfamide and cisplatin and 154 had received taxanes (paclitaxel or docetaxel)
      in addition to ifosfamide and cisplatin. The ifosfamide-cisplatin group had an
      overall response rate of 66.67% (CR, 16.42%; PR, 50.24%) and the median duration
      of response was 5.5 mo; whereas the group in which taxanes were added, showed an
      overall response rate of 73.37% (CR, 7.79%; PR, 65.58%) with a median duration of
      response of 10 mo. The toxicity in both the groups was acceptable and there was
      no mortality. We conclude that taxane-based combinations have a significant
      activity in advanced head and neck squamous cancer and warrant further studies.

PMID- 15579914
TI  - Tamoxifen and megestrol acetate for postmenopausal breast cancer: diverging
      effects on liver proteins, androgens, and glucocorticoids.
AB  - AIM: To compare the effects of tamoxifen and megestrol acetate on liver proteins,
      androgens, and glucocorticoids during adjuvant treatment for postmenopausal
      breast cancer. METHODS: A subgroup of women within a large prospective
      multicenter trial were followed with blood sampling every 3 mo during 2 yr. Women
      were randomized to receive either continuous tamoxifen 40 mg/d or repeated
      sequential treatment with tamoxifen and megestrol acetate (MA) 160 mg/d. RESULTS:
      We found profound and distinct differences between the two regimens. Tamoxifen
      increased steroid-binding proteins (SHBG and CBG) and suppressed circulating
      androgens and IGF-I. In contrast, the metabolic effects of tamoxifen were clearly
      antagonized by MA. There was a rise in IGF-I and marked suppression of steroid
      binding proteins. Levels of free testosterone were reduced by 70%. MA also caused
      apparent adrenal suppression. CONCLUSION: The different effects on
      anabolic/catabolic balance and adrenal function may relate to certain clinical
      effects during treatment.

PMID- 15579915
TI  - Sequence variant in the intron 10 of the RET oncogene in a patient with
      microfollicular thyroid carcinoma with medullar differentiation: implications for
      newly generated chi-like sequence.
AB  - Sequence alterations in the RET proto-oncogene are becoming increasingly
      important to clinical assessment of the malignant disease of the thyroid. A
      spectrum of mutations is necessary to establish comprehensive phenotype to
      genotype relationship relevant to diagnosis and therapy of thyroid malignancies.
      We aimed to append to the increasing database of these oncogenic lesions and,
      therefore, analyzed DNA from tumor tissue and constitutive DNA from a patient
      with thyroid carcinoma. Mutational screening and sequence characterization of the
      RET proto-oncogene was performed to include part of the intronic sequences. We
      report a germline sequence variant in DNA from the patient diagnosed with
      microfollicular thyroid carcinoma. The carcinoma presented not as fully developed
      medullar carcinoma (MTC) but as microfollicular carcinoma with tendency to evolve
      into MTC. We characterized the sequence variant located in the intron 10 of the
      RET oncogene as an A to G substitution denoted IVS10 + 4G. The described sequence
      alteration generates a chi-like sequence surrounded by several chi-like sequences
      with recombinational potential. Such alteration may be involved in the
      pathogenesis of the microfollicular carcinoma via genome destabilization through
      homologous recombination in the process of tumor progression. This result further
      substantiates the importance of the database correlating specific sequence
      variations in the RET gene with distinct disease phenotypes.

PMID- 15579916
TI  - Myelofibrosis in primary myelodysplastic syndromes: clinical and biological
      significance.
AB  - In a retrospective study of 236 patients with primary myelodysplastic syndromes
      (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was
      observed that fibrosis mostly occurs focally or patchy, and collagen deposits
      were found very rarely (only four patients). The histopathology of bone marrow
      biopsies revealed several differences between fibrotic and non-fibrotic MDS:
      cellularity is significantly higher, dysmegakaryopoiesis is more pronounced,
      plasmocytes and mast cells are more often increased, and disturbance of marrow
      topography (particularly of the MK- and G-line) can be found more frequently in
      MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS;
      however, there was a higher incidence in chronic myelomonocytic leukemia. The
      frequency of abnormal growth of GM-progenitors was significantly higher in the
      MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical
      data showed significantly higher WBC, more frequent presence of immature
      granulocytes, and higher percentage of myeloblasts in peripheral blood and bone
      marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life
      expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis
      (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis,
      compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore
      seems to herald a poor prognosis.

PMID- 15579917
TI  - Long-term survivors in myelodysplastic syndromes: clinical and biological
      characteristics.
AB  - Twenty-eight of 285 patients (9.8%) with primary myelodysplastic syndrome (MDS)
      survived more than 5 yr (long-term survivors). There were 21 females and 7 males,
      median age 60 yr (range 18-84 yr). None had circulating blasts, and 14 had
      refractory anemia (RA), 8 RA with ringed sideroblasts (RARS) and 6 RA with excess
      of blasts (RAEB). Thirty-seven percent of the 27 patients who were karyotyped had
      an abnormal clone, but none of them had -7/7q- or complex cytogenetic
      abnormalities. Only one of the 13 patients tested had abnormal (i.e., "leukemic")
      in vitro growth of GM progenitors. During 5 yr following the diagnosis, none of
      the 28 patients progressed to AML. Two patients with an initial diagnosis of RA
      showed progression to RAEB and CMML. After 5 yr, 23 of the 28 long-term survivors
      had stable disease (follow-up period ranged from 64 to 216 mo). One patient
      progressed to AML (113 mo after diagnosis) and another to RAEBT (80 mo after
      diagnosis). Eight asymptomatic patients were not treated and 12 patients received
      only supportive therapy. Except for 6 of 8 treated patients who responded to low
      dose Ara-C, danazol, androgens, or immunosuppressive treatment, prolonged
      survival seemed to result mainly from the natural course of the disease. Except
      for Valensia score (p=0.033), other scoring systems (Bournemouth, Dusseldorf,
      Lille, and IPSS score) proved of relatively limited value in differentiating
      between intermediate (2-5 yr) and long-term survivors.

PMID- 15579918
TI  - Synergistic effects of combination therapy employing antisense oligonucleotides
      with traditional chemotherapeutics in the PC-3 prostate cancer model.
AB  - Combination therapy including antisense oligonucleotides (ODNs) with traditional
      chemotherapeutic agents offers potential benefits by increasing the effectiveness
      of the chemotherapeutics, reducing their effective dosage, and simultaneously
      reducing toxicity. Previously we have reported that antisense ODNs specific for
      transforming growth factor-alpha (TGF-alpha) and its binding site, the epidermal
      growth factor receptor (EGFR) (MR1 and MR2, respectively), are effective against
      the PC-3 in vitro and in vivo prostate cancer models. In this series we evaluated
      these antisense ODNs in various combinations and treatment cycles with paclitaxel
      (Taxol), cyclophosphamide (Cytoxan), mitoxantrone, carboplatin, cisplatin, and
      oxaliplatin in order to identify synergistic effects.We found that when either of
      the ODNs were simultaneously administered with Taxol, no synergistic activity was
      noted. However, when sequentially administered in a series 1 d apart, a
      pretreatment with the ODN directed against TGF-alpha (6.64 microm) followed by
      Taxol (5 nm) had significantly (p <0.001) greater activity than these agents
      similarly administered in the reverse order or simultaneously. When Cytoxan was
      administered in sequence with both ODNs significantly increased growth inhibition
      was obtained compared to when Cytoxan was administered alone. A 1 d treatment of
      PC-3 cells with Cytoxan followed the next day with MR1 was significantly more
      effective (p <0.0001). The reverse order, a pretreatment with MR1 followed by
      Cytoxan, also resulted in significant additional inhibition (p=0.0004). Similarly
      sequenced, MR2 followed by Cytoxan, was also significantly more effective
      (p=0.0014) than Cytoxan treatment alone. For mitoxantrone, which was administered
      in combination therapy with ODNs: mitoxantrone with MR1 was significantly more
      inhibitory than the combination of both MR1 and MR2 ODNs (p=0.006) and also
      mitoxantrone administered alone (p=0.0012). Mitoxantrone administered with MR1
      was not significantly different from mitoxantrone given in combination with MR2.
      Although mitoxantrone and MR2 was statistically (p=00015) more inhibitory than
      mitoxantrone alone, this combination was barely more effective (p=0.04) than the
      MR1 ODN administered alone.

PMID- 15579919
TI  - Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML)
      treated with imatinib mesylate.
AB  - Survival among chronic myelogenous leukemia (CML) patients can be linked to the
      reduction in leukemic cell burden. Treatment with imatinib mesylate results in a
      high frequency of complete cytogenetic response, which can be further stratified
      using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We
      have serially monitored peripheral blood and bone marrow BCR-ABL transcripts
      using qRT-PCR in CML patients commencing imatinib therapy, and compared the
      results with bone marrow cytogenetics. Seventeen patients (aged 25-74 yr) with
      Philadelphia chromosome positive CML in first chronic phase were treated with
      imatinib targeting a dose of 400 mg/d. The median follow up is 30 mo (range 9-33
      mo). Every third month the product of the BCR-ABL fusion gene was evaluated in
      both blood and bone marrow specimens by real-time RT-PCR using the TaqMan probe
      system. In 113 simultaneously obtained blood and bone marrow samples, the BCR-ABL
      transcript values agreed well with cytogenetic data. Blood and bone marrow
      specimens gave comparable values for BCR-ABL transcripts. Before start of
      imatinib therapy there was a considerable variation in BCR-ABL transcripts among
      the patients, ranging approximately one log (base 10). Similarly, patients with a
      complete cytogenetic response following imatinib therapy had variable BCR-ABL
      transcript levels, ranging at least three logs (base 10). The major decline in
      BCR-ABL transcripts occurred within 6 mo after start of imatinib therapy. The
      decline in BCR-ABL transcripts, following imatinib therapy, appears to level off
      at 12-15 mo. Two late responders were identified with a still decreasing level in
      BCR-ABL transcripts after 24 mo of treatment. It is concluded that BCR-ABL mRNA
      quantification in peripheral blood is suitable for routine monitoring of the
      response to treatment and long-term disease status in CML, especially in patients
      who have achieved a complete cytogenetic response. A plateau in BCR-ABL
      transcripts seems to have been reached after 12-15 mo of imatinib treatment;
      however, some "late responders" are seen.

PMID- 15579920
TI  - Ifosfamide, mesna, and interferon-alpha2A combination chemoimmunotherapy in
      malignant mesothelioma: results of a single center in central anatolia.
AB  - Our aim was to determine the efficacy of ifosfamide, mesna, and interferon alpha
      combination therapy in malignant mesothelioma (MM) patients. Fourty-two patients
      (39 evaluable) with histologically proven MM were enrolled into this study from
      January 1999 to October 2002. The drug schedule consisted of a combination of
      ifosfamide, 3000 mg/m2 1-3 d intravenous infusion (iv), the uroprotective agent
      mesna, 3000 mg/m2 1-3 d iv every 3 wk, and interferon alpha2a, 4.5 MU
      subcutaneously (sc) 3 d/wk for 6 mo as first-line chemotherapy. Overall, 140
      cycles were administered to the 39 patients (median, 3.5 cycles; range, 1 to 6
      cycles). Among the 39 patients, 8 partial remissions (PR) (21%) were observed.
      Thirteen patients (33%) had stable disease for at least 8 wk and 18 (46%) had
      progressive disease. Overall survival (OAS) and progression free survival (PFS)
      for all patients were 10.0 +/- 2.9 mo (95%CI 4.3-15.7) and 5.0 +/- 1.9 mo (95%CI
      1.38-8.62), respectively. One and two year survival rates were calculated as 39%
      and 5%, respectively. All of the PR patients had the epithelial type of MM. Their
      survival time was 21.0 +/- 5.7 mo (95% CI 9.9-32.1) and significantly longer than
      that of nonresponders (p=0.0061). The toxicity of the drug combination was mild
      and well tolerated. There were no treatment-related deaths. Grade 3-4 neutropenia
      and febrile neutropenia were seen in 10 patients (26%) and 3 patients (8%),
      respectively. Chemotherapy was stopped in three patients because of renal
      function deficiency. One of these patients who had peritoneal MM required
      hemodialysis. In conclusion, this combination therapy showed encouraging
      antitumor activity with modest toxicity.

PMID- 15579921
TI  - Epithelioid sarcoma of vulva: a case report and review of the literature.
AB  - Epithelioid sarcoma of vulva is an extremely rare and aggressive tumor. In most
      patients it is asymptomatic, and the lesions are usually mistaken for benign
      processes, leading to diagnosis at later stages. We report a case of vulvar
      epithelioid sarcoma in a 51-yr-old woman presenting with a nodularity of vulva.
      Left hemivulvectomy with bilateral inguinal lymph node dissection was performed.
      There was no evidence of distant metastasis at the time of diagnosis. Following
      adjuvant chemoradiotherapy and three cycles of chemotherapy, the patient
      developed lung metastasis 4 mo after surgery and died of disseminated disease
      after 6 mo of diagnosis. Vulvar epithelioid sarcoma is rare; showing different
      behavior changing from an extremely aggressive tumor to behaviors like low-grade
      tumors. It is best treated by early diagnosis and initial eradication. Definitive
      surgery provides excellent local control and survival in low-grade tumors. The
      role of adjuvant treatment remains to be determined.

PMID- 15579922
TI  - Acute leukemia in a patient with ocular melanoma: is it induced by intraocular
      brachytherapy or only a bad fate?

PMID- 15579926
TI  - Consumer participation in the employment rehabilitation process: contextual
      factors and implications for practice.
AB  - Rehabilitation models of practice have emerged that offer persons' with
      disabilities opportunities to have an active role in the work entry or re(entry)
      process. Despite the growth and interest in empowering client involvement in
      practice, consumer views on the determinants of participation are not fully
      understood. Thus, consumer feedback on using a self-directed approach to
      employment rehabilitation was elicited to identify factors integral to their
      participation in the process. Focus groups were conducted with 35 adult consumers
      with developmental, mental health, physical and learning disabilities to gain
      insights into their involvement in a participatory approach to find employment.
      Content analysis of data revealed barriers and facilitators, which hindered or
      enabled consumer involvement in the vocational service process. This article
      discusses the importance of considering issues across the rehabilitation system,
      practice and lived contexts when implementing participatory approaches in
      vocational rehabilitation settings.

PMID- 15579927
TI  - Ratings of health and quality of life by young working people: are there
      occupational or education-based differences?
AB  - The study examines differences in self-rated health and perceived quality of life
      (QoL) among young working people according to occupation and education level.
      Subjects were extracted from a cross-sectional data set, covering questionnaire
      responses of people aged 20-74 years from the Swedish region of Ostergotland, and
      addressing individual environmental and health conditions. The emphasis was on
      males and females in paid employment aged 20-34 (n = 863). Differences in self
      rated health items and in perceived QoL were subjected to a series of t-tests.
      Two measures of individual socioeconomic position were considered - occupation
      and education. No education-based differences were found, and there were few
      differences based on occupation. Among males, manual workers reported
      significantly higher scores with regard to pain and physical function than did
      non-manual workers. Male and female manual workers scored significantly lower on
      current perceived QoL than non-manual workers. In the case of females, the
      differences between manual and non-manual workers also applied to former
      perceived QoL. Yet, after applying the Bonferroni correction, none of the
      differences observed remained significant. In line with some earlier studies, it
      appears that -- among young working adults -- the manners in which health status
      and QoL are perceived are not strongly conditional on socioeconomic position.

PMID- 15579928
TI  - Planning + practice = preparedness: a case study in injury prevention.
AB  - At 5:30 p.m. on May 8, 2003, 1,200 employees were at work at the Oklahoma City,
      Oklahoma, General Motors Production Plant when it was hit by an F4 tornado.
      Although the plant sustained extensive structural damage none of the employees
      were injured. The plant's commitment to emergency response planning, the routine
      practice of those plans through drills, tests, and education, and the smooth
      implementation of the plan at the appropriate time helped prevent injury and
      potential loss of life. This case study provides an example of effective injury
      prevention.

PMID- 15579929
TI  - The impact of vocational services and employment on people with HIV/AIDS.
AB  - The perceptions of vocational services and the impact of employment among 25
      individuals with HIV/AIDS diagnoses were explored through a qualitative study.
      Participants who ranged in age from 22 to 58, represented diverse ethnic
      backgrounds and were at various stages of the employment process. The key themes
      that emerged from the data fell into three main areas: (a) personal impact of
      vocational services, (b) programmatic qualities of vocational services, and (c)
      impact of employment. Factors that influenced each of these themes and the
      implications for rehabilitation counselors are discussed.

PMID- 15579930
TI  - Health behavior change among office workers: an exploratory study to prevent
      repetitive strain injuries.
AB  - The purpose of this evidence-based study is to investigate the impact of a multi
      component intervention on health behavior change among office/computer workers in
      preventing repetitive strain injuries. Forty office workers employed in an
      administrative office in Michigan participated in this project. The subjects
      completed a comprehensive questionnaire at three different times in 1994 and
      1995. The intervention took place between time 2 and time 3 and included posters,
      e-mail tips, mini-workshops, and activities of a Wellness Ergonomic Team. A
      theoretical model was tested to identify factors influencing healthy behaviors.
      Study findings revealed positive behavior change for 62% of the participants. The
      factors most strongly related to health behavior change appear to be self
      efficacy, the intention to change one's behavior, and perceived health status.
      Better understanding of health behavior change coupled with ergonomic
      modifications is a significant step toward the prevention of repetitive strain
      injuries resulting from computer use.

PMID- 15579931
TI  - Worker perceptions of organizational support and return-to-work policy:
      associations with post-injury job satisfaction.
AB  - This study evaluates the psychometric properties of an industry-based employee
      measure of employer responses to injuries (i.e., organizational support and
      return-to-work policies) and explores the relationship of these variables to post
      injury job satisfaction. Survey data were collected from 1438 employees with work
      related injuries in 13 construction companies and 13 transportation companies.
      Factor analyses supported the two-factor structure of the scale, and both
      organizational support and return-to-work policies were independently associated
      with post-injury job satisfaction. The results suggest a need for understanding
      organizational responses to injuries, employee perceptions of injury response,
      and the impact of both on organizational outcomes.

PMID- 15579932
TI  - Construction managers' perceptions of construction safety practices in small and
      large firms: a qualitative investigation.
AB  - BACKGROUND AND GOALS: Despite the institution of explicit safety practices in
      construction, there continue to be exceedingly high rates of morbidity and
      mortality from work-related injury. This study's purpose was to identify, compare
      and contrast views of construction managers from large and small firms regarding
      construction safety practices. A complementary analysis was conducted with
      construction workers. METHODS: A semi-structured interview guide was used to
      elicit information from construction managers (n = 22) in a series of focus
      groups. Questions were designed to obtain information on direct safety practices
      and indirect practices such as communication style, attitude, expectations, and
      unspoken messages. Data were analyzed using thematic content analysis. RESULTS:
      Managers identified a broad commitment to safety, worker training, a changing
      workplace culture, and uniform enforcement as key constructs in maintaining safe
      worksites. Findings indicate that successful managers need to be involved,
      principled, flexible, and innovative. Best practices, as well as unsuccessful
      injury prevention programs, were discussed in detail. Obstacles to consistent
      safety practice include poor training, production schedules and financial
      constraints. CONCLUSIONS: Construction managers play a pivotal role in the
      definition and implementation of safety practices in the workplace. In order to
      succeed in this role, they require a wide variety of management skills, upper
      management support, and tools that will help them instill and maintain a positive
      safety culture. Developing and expanding management skills of construction
      managers may assist them in dealing with the complexity of the construction work
      environment, as well as providing them with the tools necessary to decrease work
      related injuries.

PMID- 15579933
TI  - Construction workers' perceptions of management safety practices: a qualitative
      investigation.
AB  - BACKGROUND AND GOALS: The purpose of this study was to identify perceptions of
      management safety practices from the viewpoint of union and nonunion construction
      workers. A complementary investigation was conducted with construction managers.
      METHODS: A semi-structured interview guide was used to elicit information from 64
      workers (95% male) in ten focus groups. Questions were designed to elicit
      information about management practices that facilitate or discourage safe working
      conditions, including communication style, attitude, expectations, and unspoken
      messages. Data were analyzed using thematic content analysis. RESULTS: Workers
      identified management commitment to safety, concern for workers, congruence
      between spoken messages and practice, professionalism, and communication skills
      as key qualities in successful managers. Workers provided vivid examples of
      excellent and poor management strategies. CONCLUSIONS: Construction managers play
      a pivotal role in the definition and implementation of safety practices in the
      workplace and workers look to them for guidance and modeling. Given the high
      rates of injury in construction, deeply imbedded protective policies that rely on
      input from a broad range of stakeholders, including construction workers, should
      be developed.

PMID- 15579934
TI  - Predicting the effect of disability on employment status and income.
AB  - Research shows that participation in employment contributes to life satisfaction
      for persons with disabilities [18]. Title I of the Americans with Disabilities
      Act (ADA) sought to prohibit discrimination against persons with disabilities in
      the workplace, however, the ADA's effectiveness remains controversial. This
      research utilizes data from the disability supplement of the 2000 Behavioral Risk
      Factor Surveillance System to examine the impact of disability status on
      predicting employment status and income. Confounding variables such as gender,
      age, educational level, race and marital/parental status are examined regarding
      their influence on results. Results from analysis utilizing zero-order
      correlation, linear and logistic regression analysis techniques revealed that
      disability status has a significant predictive effect on inability to work.
      Furthermore, results continue to show that despite legislation, the higher the
      level of disability, the lower the employment status (those employed for wages)
      and income. Finally, disability status, coupled with being female or decreased
      educational level, consistently shows significance in predicting lower employment
      status and income than men or non-minorities with disabilities. Future research
      opportunities and policy implications are discussed with regard to the results
      presented.

PMID- 15579935
TI  - What do employers think about employing people with experience of mental illness
      in New Zealand workplaces?
AB  - The researchers investigated employers' experiences with individuals with a
      mental illness and in their workplaces. Seventy-two business owners or human
      resource managers were interviewed. Most knew the prospective employee's health
      background prior to deciding to employ them. The majority of the reported
      experiences with employed individuals were very positive. Key strategies the
      employers or managers reported using to support employees were: to create
      trustworthy relationships, to work through issues and to seek external support.

PMID- 15579936
TI  - K2[HCr2AsO10]: redetermination of phase II and the predicted structure of phase
      I.
AB  - Our prediction that phase II of dipotassium hydrogen chromatoarsenate,
      K(2)[HCr(2)AsO(10)], is ferroelectric, based on the analysis of the atomic
      coordinates by Averbuch-Pouchot, Durif & Guitel [Acta Cryst. (1978), B34, 3725
      3727], led to an independent redetermination of the structure using two separate
      crystals. The resulting improved accuracy allows the inference that the H atom is
      located in the hydrogen bonds of length 2.555 (5) angstroms which form between
      the terminal O atoms of shared AsO(3)OH tetrahedra in adjacent HCr(2)AsO(10)(2-)
      ions. The largest atomic displacement of 0.586 angstroms between phase II and the
      predicted paraelectric phase I is by these two O atoms. The H atoms form helices
      of radius approximately 0.60 A about the 3(1) or 3(2) axes. Normal probability
      analysis reveals systematic error in seven or more of the earlier atomic
      coordinates.

PMID- 15579937
TI  - High-pressure synthesis of nu-DyBO3.
AB  - nu-Dysprosium borate (nu-DyBO(3)) was synthesized under conditions of high
      temperature and pressure in a Walker-type multi-anvil apparatus at 3 GPa and 1323
      K. The compound is isotypic with the already known nu-samarium and nu-europium
      orthoborates.

PMID- 15579938
TI  - GdAlO3 perovskite.
AB  - Flux-grown gadolinium aluminate perovskite, GdAlO(3), was examined using single
      crystal 0.7 angstroms-wavelength synchrotron X-ray diffraction. In the context of
      other well categorized rare earth aluminate (RAlO(3)) perovskite phases, the
      orthorhombic Pnma symmetry determined for the current compound is unsurprising.
      Corner-linked AlO(6) octahedra form the structural backbone of RAlO(3)
      perovskites and distort to accommodate the various rare earth ions in the
      structural voids. For GdAlO(3), the octahedral distortion, characterized by
      tilting of the octahedra about the shortest R-Al-R vectors, and octahedral
      deformation, characterized by strain of the octahedra along those axes, are in
      accordance with trends in the RAlO(3) series.

PMID- 15579939
TI  - Low-dimensional compounds containing cyano groups. X. (Dicyanamido
      kappaN1)bis(1,10-phenanthroline-kappa2N,N')copper(II) perchlorate.
AB  - The title compound, [Cu(C(2)N(3))(C(12)H(8)N(2))(2)]ClO(4), represents a
      relatively rare class of compounds with dicyanamide coordinated in a monodentate
      manner. The structure is formed by the [Cu{N(CN)(2)}(phen)(2)](+) complex cation
      (phen is 1,10-phenanthroline) and an uncoordinated ClO(4)(-) anion. The Cu atom
      is five-coordinate, with a slightly distorted trigonal-bipyramidal environment.
      The dicyanamide ligand is coordinated through one nitrile N atom in the
      equatorial plane, at a distance of 2.033 (6) angstroms from the metal. The two
      axial Cu-N distances are similar [mean 1.999 (4) angstroms] and are substantially
      shorter than the remaining two equatorial Cu-N bonds [mean 2.087 (1) angstroms].

PMID- 15579940
TI  - catena-Poly[[(di-2-pyridylamine)silver(I)]-mu-nicotinato] and catena-poly[[(di-2
      pyridylamine)silver(I)]-mu-2,6-dihydroxybenzoato].
AB  - In catena-poly[[(di-2-pyridylamine-kappa(2)N,N')silver(I)]-mu-nicotinato
      kappa(2)N:O], [Ag(C(6)H(4)NO(2))(C(10)H(9)N(3))](n), the Ag(I) atom is
      tetracoordinated by two N atoms from the di-2-pyridylamine (BPA) ligand [Ag-N =
      2.3785 (18) and 2.3298 (18) angstroms] and by one N atom and one carboxylate O
      atom from nicotinate ligands [Ag-N = 2.2827 (15) angstroms and Ag-O = 2.3636 (14)
      angstroms]. Bridging by nicotinate N and O atoms generates a polymeric chain
      structure, which extends along [100]. The carboxyl O atom not bonded to the Ag
      atom takes part in an intrachain C-H...O hydrogen bond, further stabilizing the
      chain. Pairs of chains are linked by N-H...O hydrogen bonds to generate ribbons.
      There are no pi-pi interactions in this complex. In catena-poly[[(di-2
      pyridylamine-kappa(2)N,N')silver(I)]-mu-2,6-dihydroxybenzoato-kappa(2)O(1):O(2)],
      [Ag(C(7)H(5)O(4))(C(10)H(9)N(3))](n), the Ag(I) atom has a distorted tetrahedral
      coordination, with three strong bonds to two pyridine N atoms from the BPA ligand
      [Ag-N = 2.286 (5) and 2.320 (5) angstroms] and to one carboxylate O atom from the
      2,6-dihydroxybenzoate ligand [Ag-O = 2.222 (4) angstroms]; the fourth, weaker, Ag
      atom coordination is to one of the phenol O atoms [Ag...O = 2.703 (4) angstroms]
      of an adjacent moiety, and this interaction generates a polymeric chain along
      [100]. Pairs of chains are linked about inversion centers by N-H...O hydrogen
      bonds to form ribbons, within which there are pi-pi interactions. The ribbons are
      linked about inversion centers by pairs of C-H...O hydrogen bonds and additional
      pi-pi interactions between inversion-related pairs of 2,6-dihydroxybenzoate
      ligands to generate a three-dimensional network.

PMID- 15579941
TI  - trans-Diaquabis(5-carboxy-1H-imidazole-4-carboxylato-kappa2N3,O4)cobalt(II) 4,4'
      bipyridine solvate.
AB  - In the title compound, [Co(C(5)H(3)N(2)O(4))(2)(H(2)O)(2)].C(10)H(8)N(2), the Co
      atom is trans-coordinated by two pairs of N and O atoms from two monoanionic 4,5
      dicarboxyimidazole ligands, and by two O atoms from two coordinated water
      molecules, in a distorted octahedral geometry. The 4,4'-bipyridine solvent
      molecule is not involved in coordination but is linked by an N-H...N hydrogen
      bond to the neutral [Co(C(5)H(3)N(2)O(4))(2)(H(2)O)(2)] molecule. Both molecules
      are located on inversion centers. The crystal packing is stabilized by N-H...N
      and O-H...O hydrogen bonds, which produce a three-dimensional hydrogen-bonded
      network. Offset pi-pi stacking interactions between the pyridine rings of
      adjacent 4,4'-bipyridine molecules were observed, with a face-to-face distance of
      3.345 (1) angstroms.

PMID- 15579942
TI  - Bis(ethylenediammonium) decaaquadisodium decavanadate,
      (C2H10N2)2[Na2(H2O)10][V10O28].
AB  - In the title compound, the decavanadate anion, [V(10)O(28)](6-), and the bridged
      [Na(2)(H(2)O)(10)](2+) dication lie across inversion centers. The charge balance
      is achieved by ethylenediammonium cations, H(3)NCH(2)CH(2)NH(3)(2+), which are
      disordered. The decavanadate anions are surrounded by the [Na(2)(H(2)O)(10)](2+)
      dications, thus forming layers, and the ethylenediammonium cations are located
      between these layers.

PMID- 15579943
TI  - (eta6-Biphenyl)tricarbonylchromium and mu-(eta6:eta6)-biphenyl
      bis(tricarbonylchromium).
AB  - The title compounds, [Cr(C(12)H(10))(CO)(3)] and [Cr(2)(C(12)H(10))(CO)(6)],
      serve as a fundamental standard of comparison for other mono- and polysubstituted
      (eta(6)-biphenyl)tricarbonylchromium compounds. (eta(6)
      Biphenyl)tricarbonylchromium has a typical piano-stool coordination about the Cr
      center, and the dihedral angle between the planes of the phenyl rings is 23.55
      (5) degrees . The corresponding angle in mu-(eta(6):eta(6))-biphenyl
      bis(tricarbonylchromium) is 0 degrees because the molecule occupies a
      crystallographic inversion center; the Cr atoms reside on opposite sides of the
      biphenyl ligand. Density functional theory and natural bonding orbital theory
      analyses were used to scrutinize the geometry of these and closely related
      compounds to explain important structural features.

PMID- 15579944
TI  - 4,4'-Thiodipyridinium tetrachlorocopper(II).
AB  - The title compound, (C(10)H(10)N(2)S)[CuCl(4)], was obtained by the reaction of
      cupric chloride with pyridine-4-thiol in a mixture of acetonitrile and
      tetrahydrofuran, suggesting that the desulfurization and coupling reactions of
      pyridine-4-thiol occurred in the presence of the Cu(2+) ion. X-ray diffraction
      analysis reveals the presence of one 4,4'-thiodipyridinium cation, H(2)bps(2+),
      and one [CuCl(4)](2-) anion. The cations interact with the anions via N-H...Cl
      hydrogen-bonding interactions to form a closed 'chair' conformation.

PMID- 15579945
TI  - catena-Poly[[[mu-pyrazine-kappa2N:N'-disilver(I)]-di-mu-pyrazine-kappa4N:N']
      bis(trifluoromethanesulfonate) dihydrate].
AB  - The title compound, {[Ag(2)(C(4)H(4)N(2))(3)](CF(3)SO(3))(2).2H(2)O}(n), is a
      polymeric pyrazine-silver(I) complex. Each Ag(I) ion is three-coordinated by N
      atoms of three different pyrazine ligands, forming a T-shaped coordination
      configuration. In the crystal structure, uncoordinated water molecules are linked
      to trifluoromethanesulfonate anions through intermolecular O-H...O hydrogen
      bonds. There are weaker Ag...O interactions involving the water and sulfonate O
      atoms.

PMID- 15579946
TI  - catena-Poly[[(benzoato-kappaO)silver(I)]-mu-2-aminopyrimidine-kappa2N1:N3].
AB  - The title complex, [Ag(C(7)H(5)O(2))(C(4)H(5)N(3))](n), is a polymer based on a
      mononuclear silver(I)-centered fragment. The Ag(I) atom is trigonally coordinated
      by two N atoms from two 2-aminopyrimidine ligands and one O atom from one
      benzoate anion, giving zigzag polymeric chains with an [-Ag-N-C-N-](n) backbone
      running along the a axis. It is proposed that intermolecular hydrogen bonding
      drives the formation of the chain polymer.

PMID- 15579947
TI  - Dichlorobis(cumylcyclopentadienyl)titanium(IV).
AB  - The title compound, [Ti(C(14)H(15))(2)Cl(2)], belongs to a class of complexes
      that are potentially active as pre-catalysts in the stereospecific polymerization
      of olefins. In the crystal structure, molecules lie on C(2) axes with pseudo
      tetrahedral coordination around the Ti atoms. Conformational features of the
      compound are discussed, in conjunction with calculations that demonstrate the
      existence of other energetically favorable conformations in addition to that
      found in the reported crystal structure.

PMID- 15579948
TI  - The copper(II) complexes di-mu-bromo-bis{[2,6-bis(pyrazol-1
      yl)pyridine]perchloratocopper(II)} and [2,6-bis(pyrazol-1
      yl)pyridine]dibromocopper(II).
AB  - The two title compounds, di-mu-bromo-bis{[2,6-bis(pyrazol-1-yl-kappaN(2))pyridine
      kappaN](perchlorato-kappaO)copper(II)},
      [Cu(2)Br(2)(ClO(4))(2)(C(11)H(9)N(5))(2)], (I), and [2,6-bis(pyrazol-1
      yl)pyridine]dibromocopper(II), [CuBr(2)(C(11)H(9)N(5))], (II), were synthesized
      by only slight modifications of the same reaction; compound (II) was formed by
      adding one molar equivalent of pyrazole (C(3)N(2)H(4)) to the reaction mixture of
      (I). Compound (I) is a bromo-bridged dinuclear copper(II) compound stabilized by
      weak interactions with the perchlorate anions (ClO(4)(-)), while (II) is a
      related mononuclear species, which has a distorted square-pyramidal geometry.

PMID- 15579949
TI  - Poly[methylammonium tris(mu(2)-formato-kappa2O:O')cobalt(II)].
AB  - The structure of the title compound, {(CH(6)N)[Co(CHO(2))(3)]}(n), consists of a
      three-dimensional net of central Co(II) ions connected via formate
      (methanediolate) bridges. The negative charge is compensated by protonated
      methylamine cations. The CoO(6) chromophores form slightly distorted octahedra,
      which are bridged by C atoms of formate groups. The central Co atom lies on an
      inversion center and most of the other atoms lie on an m plane.

PMID- 15579950
TI  - Butane-1,4-diamine zinc(II) hydrogen phosphite.
AB  - The title compound, poly[zinc(II)-mu-butane-1,4-diamine-mu-(hydrogen phosphito)]
      (C(4)H(12)N(2))(0.5)[ZnHPO(3)], is a hybrid organic-inorganic solid built up from
      1,4-diaminobutane molecules, Zn(2+) cations (coordinated by three O atoms and one
      N atom) and HPO(3)(2-) hydrogen phosphite groups. The organic species bonds to
      the Zn atom as an unprotonated ligand, resulting in it acting as a bridge between
      infinite ZnHPO(3) layers, which propagate in (100). The complete butane-1,4
      diamine species is generated from a H(2)N(CH(2))(2)- half molecule by inversion
      symmetry. The zincophosphite sheets contain polyhedral four- and eight-membered
      rings in a 4.8(2) topology.

PMID- 15579951
TI  - beta-[H2N(CH2)2NH2]0.5[ZnHPO3], a second modification of ethylenediamine zinc
      hydrogen phosphite.
AB  - The title compound, poly[dizinc(II)-mu-ethylenediamine-di-mu-(hydrogen
      phosphito)], beta-[H(2)N(CH(2))(2)NH(2)](0.5)[ZnHPO(3)] or
      [Zn(2)(HPO(3))(2)(C(2)H(8)N(2))](n), is a hybrid organic/inorganic solid built up
      from ethylenediamine molecules (which lie about inversion centres), Zn(2+)
      cations (coordinated by three O atoms and one N atom) and HPO(3)(2-) hydrogen
      phosphite groups. The organic species bond to the Zn atom as unprotonated
      ligands, acting as bridges between infinite ZnHPO(3) layers that propagate as
      very buckled (001) sheets. The zincophosphite sheets contain polyhedral four- and
      eight-membered rings in a 4.8(2) topology. beta
      [H(2)N(CH(2))(2)NH(2)](0.5).ZnHPO(3) complements the previously described alpha
      modification of the same stoichiometry [Rodgers & Harrison (2000). Chem. Commun.
      pp. 2385-2386].

PMID- 15579952
TI  - Bis[(R)-3,5-dichloro-N-(1-phenylethyl)salicylideneaminato-kappa2N,O]copper(II)
      and bis[(R)-3-ethoxy-N-(1-phenylethyl)salicylideneaminato-kappa2N,O]copper(II).
AB  - The title compounds, [Cu(C(15)H(12)Cl(2)NO)(2)], (I), and
      [Cu(C(17)H(18)NO(2))(2)], (II), both adopt a compressed tetrahedral trans
      [CuN(2)O(2)] coordination geometry, the molecules having an umbrella conformation
      overall. These complexes differ from one another with respect to the 1
      phenylethylamine moieties, the direction of the benzene rings being either inside
      [in (I)] or inside and outside [in (II)] of the molecules. The crystals of (I)
      and (II) have Delta(R,R) and Lambda(R,R) absolute configurations, respectively.

PMID- 15579953
TI  - Bis(tetra-n-butylammonium) (mu-N,N'-diselenium
      dinitride)bis[tribromopalladate(II)].
AB  - The reaction of Se(4)N(4) with (Bu(4)N)(2)[Pd(2)Br(6)] gives the title compound,
      (C(16)H(36)N)(2)[Pd(2)Br(6)(N(2)Se(2))], in good yield. The
      [Pd(2)(Se(2)N(2))Br(6)](2-) anion lies on an inversion centre, and therefore the
      asymmetric unit contains half a formula unit. The crystal structure confirms the
      coordination of the Se(2)N(2) unit to Pd through the N atoms, as previously
      assigned by IR spectroscopic analysis [Kelly, Slawin & Soriano-Rama (1997). J.
      Chem. Soc. Dalton Trans. pp. 559-562]. The title compound contains the longest Pd
      N bond so far observed for such systems.

PMID- 15579954
TI  - Sodium 1-carboxycyclopropane-1-carboxylate cyclopropane-1,1-dicarboxylic acid
      monohydrate.
AB  - In the title type B(2) acid salt, Na(LH)(LH(2)).H(2)O [LH(2) =
      C(2)H(4)C(CO(2)H)(2)] or Na(+).C(5)H(5)O(4)(-).C(5)H(6)O(4).H(2)O, the vertices
      of a distorted octahedron centred on each Na(+) cation are defined by six O
      atoms, one from a water molecule, one from an internally hydrogen-bonded LH(-)
      anion and four from three neutral LH(2) acid molecules. Chains of edge-sharing
      O(6) octahedra are stabilized by hydrogen bonds, which interconnect the donor
      H(2)O and LH(2) molecules and LH(-) anions. In particular, the LH(2) molecule
      donates H atoms to LH(-) and H(2)O and forgoes the internal hydrogen bond which
      stabilizes the free acid and all of its characterized salts.

PMID- 15579955
TI  - Ethyltriphenylphosphonium perrhenate and (iodomethyl)triphenylphosphonium
      perrhenate.
AB  - Ethyltriphenylphosphonium perrhenate, (C(20)H(20)P)[ReO(4)], and
      (iodomethyl)triphenylphosphonium perrhenate, (C(19)H(17)IP)[ReO(4)], have been
      crystallized from 2-propanol. Both crystal structures consist of phosphonium
      cations and perrhenate anions. The cations show the typical propeller-like
      geometry. In both crystals, the positions of the nearly tetrahedral anions are
      stabilized by weak C-H...O hydrogen bonds, and for the latter compound, I...pi
      interactions also occur.

PMID- 15579956
TI  - catena-Poly[[(pyridin-4-ol-kappaN)silver(I)]-mu-pyridin-4-olato-kappa2N:O].
AB  - The title complex, [Ag(C(5)H(4)NO)(C(5)H(5)NO)](n), consists of a polymeric
      neutral chain involving both a neutral pyridin-4-ol ligand and a deprotonated
      pyridin-4-olate monoanion. The Ag(I) atom shows a T-shaped coordination geometry,
      defined by one N atom of the pyridin-4-ol and one O and one N atom of two
      independent pyridin-4-olate bridges; the N-Ag-N moiety is approximately linear.
      The polymeric chains are connected via strong O-H...O hydrogen bonds and offset
      pi-pi interactions into a three-dimensional network.

PMID- 15579957
TI  - Poly[[bis(pyridine-kappaN)copper(II)]-mu(3)-5-hydroxyisophthalato
      kappa3O:O':O''].
AB  - In the title compound, [Cu(C(8)H(4)O(5))(C(5)H(5)N)(2)](n) or [Cu(OH
      BDC)(py)(2)](n) (where OH-H(2)BDC is 5-hydroxyisophthalic acid and py is
      pyridine), the Cu atoms are coordinated by two N atoms from the pyridine ligands
      and by three O atoms from hydroxyisophthalate ligands in a highly distorted
      triangular bipyramidal environment, with Cu-O distances in the range 1.941 (4)
      2.225 (5) A and Cu-N distances of 2.014 (6) and 2.046 (6) A. The [Cu(OH-BDC)](n)
      two-dimensional network is built up from interlocking 22-, 15- and eight-membered
      rings via sharing of Cu atoms and O-H...O hydrogen bonds. Consolidation of the
      packing structure is achieved by edge- or point-to-face C-H...pi interactions and
      offset or slipped pi-pi stacking interactions.

PMID- 15579958
TI  - Poly[aquaneodymium(III)-mu5-2-oxido-5-sulfonatobenzoato].
AB  - The title compound, [Nd(C(7)H(3)O(6)S)(H(2)O)](n) or [Nd(SSA)(H(2)O)](n) (H(3)SSA
      is 5-sulfosalicylic acid), was synthesized by the hydrothermal reaction of
      Nd(2)O(3) with H(3)SSA in water. The compound forms a three-dimensional network
      in which the asymmetric unit contains one Nd(III) atom, one SSA ligand and one
      coordinated water molecule. The central Nd(III) ion is eight-coordinate, bonded
      to seven O atoms from five different SSA ligands [Nd-O = 2.405 (4)-2.612 (4)
      angstroms] and one aqua O atom [Nd-OW = 2.441 (4) angstroms].

PMID- 15579959
TI  - The first di-mu-hydroxo-bridged binuclear copper complex containing a bis
      guanidine ligand.
AB  - The present structure determination of di-mu-hydroxo-bis{[N,N'
      bis(dipiperidinomethylene)propane-1,3-diamine-kappa(2)N,N']copper(II)}
      bis(hexafluorophosphate), [Cu(2)(OH)(2)(C(25)H(46)N(6))(2)](PF(6))(2), is the
      first to crystallographically characterize a Cu(2)(mu-OH)(2) complex with a
      bidentate guanidine ligand. The cation lies on a crystallographic inversion
      centre and shows planar fourfold coordination of the copper centres. The Cu(2)(mu
      OH)(2) species can be distinguished from Cu(2)(mu-O)(2) by the Cu-O bond lengths.
      The packing is determined by strong intermolecular anion-cation hydrogen bonds.

PMID- 15579960
TI  - Chlorobis[N-ethoxycarbonyl-N'-(p-methoxyphenyl)thiourea-kappaS]copper(I).
AB  - The title copper(I) complex, [CuCl(C(11)H(14)N(2)O(3)S)(2)], was synthesized by
      the redox reaction of cupric chloride with the corresponding thiourea derivative
      as reducing agent. The Cu(I) coordination environment is trigonal planar,
      involving two S atoms and one Cl atom. The presence of intramolecular hydrogen
      bonds leads to the formation of a cis conformation and promotes the stability of
      the complex.

PMID- 15579961
TI  - Solvates of zafirlukast.
AB  - The crystal structures of three solvates of zafirlukast [systematic name:
      cyclopentyl N-{1-methyl-3-[2-methyl-4-(o-tolylsulfonylaminocarbonyl)benzyl]-1H
      indol-5-yl}carbamate], viz. the monohydrate, C(31)H(33)N(3)O(6)S.H(2)O, (I), the
      methanol solvate, C(31)H(33)N(3)O(6)S.CH(3)OH, (II), and the ethanol solvate,
      C(31)H(33)N(3)O(6)S.C(2)H(5)OH, (III), have been determined by single-crystal X
      ray diffraction analysis. All three compounds crystallize in the monoclinic
      crystal system. Zafirlukast adopts a similar Z-shaped conformation in all three
      solvates. The methanol and ethanol solvates are isostructural. The packing of the
      zafirlukast molecules in all three crystal structures is similar and is expressed
      by hydrogen-bonded molecules that are related by translation, along (101) in (I)
      and along the b axis in (II) and (III). The methanol and ethanol solvent
      molecules are hydrogen bonded to two molecules of zafirlukast. The water
      molecule, on the other hand, acts as a connector via hydrogen bonds between three
      molecules of zafirlukast. The solvent molecules are not released at temperatures
      below the melting points of the solvates.

PMID- 15579962
TI  - Butane-1,4-diyl bis(chloroacetate).
AB  - The title compound, C(8)H(12)Cl(2)O(4), lies about an inversion centre. The
      molecular conformation is characterized by a tgt-gt conformation for the
      butanedioxy moiety and a trans conformation for the ClCH(2)-C(=O)O bond. The
      molecular packing is stabilized by a network of weak CH(2)...O=C intermolecular
      hydrogen bonds, where each molecule interacts with its four closest neighbours.

PMID- 15579963
TI  - 4,4'-Bis(N,N-diethylamino)-2,2'-bipyridine.
AB  - The title compound, C(18)H(26)N(4), contains two almost identical independent
      molecules that lie about inversion centres. Each molecule has a planar bipyridine
      nucleus and two terminal diethylamine groups oriented at almost right angles to
      the core. These diethylamine branches act as spacers, producing a very open
      structure with one of the lowest densities reported among related compounds. The
      most important intermolecular interactions are of the C-H...pi type, which
      connect non-equivalent moieties.

PMID- 15579964
TI  - Brucine and two solvates.
AB  - The crystal structures of brucine (2,3-dimethoxystrychnidin-10-one),
      C(23)H(26)N(2)O(4), brucine acetone solvate, C(23)H(26)N(2)O(4).C(3)H(6)O, and
      brucine 2-propanol solvate dihydrate, C(23)H(26)N(2)O(4).C(3)H(7)O.2H(2)O, have
      been determined. Crystals of brucine and its 2-propanol solvate dihydrate exhibit
      similar monolayer sheet packing, whereas crystals of the acetone solvate adopt a
      different mode of packing, as brucine pillars. The solvent appears to control the
      brucine self-assembly on the basis of common donor-acceptor properties of the
      surfaces.

PMID- 15579965
TI  - Di-2-pyridyl ketone 4-methyl-4-phenylthiosemicarbazone.
AB  - The molecule of the title compound, C(19)H(17)N(5)S, adopts a Z configuration
      about the azomethine bond and exists as the thione tautomer. The overall
      structure of the molecule is distributed in four different planes. An
      intramolecular hydrogen bond involving the pyridyl N atom and the H atom attached
      to the hydrazine N atom leads to the formation of a six-membered ring.

PMID- 15579966
TI  - Self-inclusion in 5,11,17,23-tetra-tert-butyl-26,27,28-trihydroxy-25
      (methoxycarbonylmethoxy)calix[4]arene chloroform trisolvate.
AB  - The title compound, C(47)H(60)O(6).3CHCl(3), is the first example of a lower-rim
      mono-ester calixarene derivative to be crystallographically characterized. The
      cone conformation adopted by the macrocycle is stabilized by three intramolecular
      hydrogen bonds. Self-inclusion of the methyl ester chain in the cavity of an
      adjacent molecule gives rise to infinite chains parallel to the c axis. C-H...pi
      interactions involving the methyl group most imbedded in the cavity contribute to
      the stabilization of the system.

PMID- 15579967
TI  - The first bipodal thiocarbamic acid ester, O,O'-diethyl N,N'-(p
      phenylenedicarbonyl)bis(thiocarbamate).
AB  - The title compound, C(14)H(16)N(2)O(4)S(2), is the first reported X-ray
      crystallographic structure determination of a bipodal O-alkyl N
      benzoylthiocarbamate. This compound crystallizes in a cis-S,O orientation (Z,Z'
      configuration), with the two S/O moieties anti relative to one another, as
      indicated by the twofold rotation axis located at the center of the benzene ring.

PMID- 15579968
TI  - Quinoline-2(1H)-thione, a structure with Z' = 8.
AB  - The title compound, C(9)H(7)NS, crystallizes as the thione tautomer with Z' = 8
      (four independent dimers with local inversion symmetry via two N-H...S=C hydrogen
      bond systems). The dimers are arranged in chains parallel to [-110], each chain
      being crystallographically independent. These chains are associated into layers
      via stacking of ring systems. The Z' value can be rationalized in terms of a
      factor 2 for dimer formation without crystallographic symmetry and an additional
      factor 4 for differing stacking environments.

PMID- 15579969
TI  - L-Methioninium chloride and L-selenomethioninium chloride at 103 K.
AB  - The crystal structures of the title compounds, (S)-1-carboxy-3
      (methylsulfanyl)propanaminium chloride, C(5)H(12)NO(2)S(+).Cl(-), and (S)-1
      carboxy-3-(methylselanyl)propanaminium chloride, C(5)H(12)NO(2)Se(+).Cl(-), are
      isomorphous. The protonated L-methionine and L-selenomethionine molecules have
      almost identical conformations and create very similar contacts with the Cl(-)
      anions in the crystal structures of both compounds. The amino acid cations and
      the Cl(-) anions are linked viaN-H...Cl(-) and O-H...Cl(-) hydrogen bonds.

PMID- 15579970
TI  - Isomeric nitrophthalimides: sheets built from N-H...O and C-H...O hydrogen bonds.
AB  - Molecules of 3-nitrophthalimide, C(8)H(4)N(2)O(4), are linked into sheets by a
      combination of one N-H...O hydrogen bond [H...O = 1.99 angstroms, N...O = 2.8043
      (14) angstroms and N-H...O = 176 degrees] and two independent C-H...O hydrogen
      bonds [H...O = 2.36 and 2.56 angstroms, C...O = 3.1639 (16) and 3.4386 (16)
      angstroms, and C-H...O = 142 and 153 degrees], and these sheets are linked into
      pairs by a single pi-pi stacking interaction. Molecules of isomeric 4
      nitrophthalimide are linked into sheets by a combination of one three-centre N
      H...(O)(2) hydrogen bond [H...O = 2.14 and 2.55 angstroms, N...O = 2.974 (3) and
      3.231 (3) angstroms, N-H...O = 151 and 131 degrees, and O...H...O = 76 degrees]
      and two independent two-centre C-H...O hydrogen bonds [H...O = 2.38 and 2.54
      angstroms, C...O = 3.257 (4) and 3.452 (4) angstroms, and C-H...O = 156 and 168
      degrees].

PMID- 15579971
TI  - Secondary interactions in 3-bromopyridinium tribromoacetate.
AB  - The title compound, C(5)H(5)BrN(+).C(2)Br(3)O(2)(-), crystallizes with Z' = 2.
      The residues pack in two distinct (but interconnected) types of layer, namely,
      layers parallel to (102), in which the residues are connected by classical N
      H...O hydrogen bonds, C-H...O interactions and Br...Br contacts, and anion layers
      parallel to the ab plane, connected by Br...O interactions. The two formula units
      are topologically equivalent with respect to all these contacts.

PMID- 15579972
TI  - Four bromo-substituted pyrazoline and isoxazolinone spiro derivatives.
AB  - Conformational analyses and a structural comparison of the four spiro compounds 3
      bromo-1,9-diphenyl-4-p-tolyl-7-oxa-1,2,8-triazaspiro[4.4]nona-2,8-dien-6-one,
      (I), C(24)H(18)BrN(3)O(2), 3-bromo-4-(4-methoxyphenyl)-1,9-diphenyl-7-oxa-1,2,8
      triazaspiro[4.4]nona-2,8-dien-6-one, (II), C(24)H(18)BrN(3)O(3), 3-bromo-4-(4
      chlorophenyl)-1,7,9-triphenyl-1,2,7,8-tetraazaspiro[4.4]nona-2,8-dien-6-one,
      (III), C(29)H(20)BrClN(4)O, and 3-bromo-1,7,9-triphenyl-4-p-tolyl-1,2,7,8
      tetraazaspiro[4.4]nona-2,8-dien-6-one, (IV), C(30)H(22.89)Br(1.11)N(4)O, are
      presented. The molecular structures are rather similar, which is as expected
      since the compounds are all products of concerted 1,3-dipolar attack on (Z)-4
      arylidene oxazolone and pyrazolone derivatives. The observed conformations tend
      to favour extended pi conjugation of the benzene rings and other pi systems, as
      shown by a comparison of selected geometric parameters of the four structures.

PMID- 15579973
TI  - 6-Aza-2'-deoxy-2'-arabinofluorouridine, a 2'-deoxyribonucleoside with an N-sugar
      conformation in the solid state and in solution.
AB  - In the title compound, 2-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,2,4
      triazine-3,5(2H,4H)-dione, C(8)H(10)FN(3)O(5), the torsion angle of the N
      glycosylic bond is anti [chi = -125.37 (13) degrees]. The furanose moiety adopts
      the N-type sugar pucker ((3)T(2)), with P = 359.2 degrees and tau(m) = 31.4
      degrees. The conformation around the C4'-C5' bond is antiperiplanar (trans), with
      a torsion angle gamma of 177.00 (11) degrees. A network is formed via hydrogen
      bonds from the nucleobases to the sugar residues, as well as through hydrogen
      bonds between the sugar moieties.

PMID- 15579974
TI  - Imino Diels-Alder adducts. I. Two furo[3,2-c]quinoline diastereoisomers.
AB  - The structures of two diastereoisomers of 9-chloro-8-fluoro-4-phenyl
      2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinoline, C(17)H(15)ClFNO, are very similar.
      The orientation of the furan ring, as a result of its fusion to the quinoline
      nucleus, constitutes the significant difference between the two structures. The
      dihedral angles between the furan and phenyl rings are 73.4 (1) and 63.8 (1)
      degrees.

PMID- 15579975
TI  - 11-Methyl-2,3-benzodipyrrin-1-one.
AB  - The title compound {alternative names: 11-methyl-2,3-benzopyrromethenone and 3
      [(1-methylpyrrol-2-yl)methylidene]-2,3-dihydro-1H-isoindol-1-one},
      C(14)H(12)N(2)O, was prepared by the base-catalysed condensation of phthalimidine
      with 2-formyl-1-methylpyrrole; yellow orthorhombic crystals, space group Pbca,
      were obtained from ethanol. The molecule is almost planar, having Z(
      )antiperiplanar geometry. The molecules are arranged in pairs with intermolecular
      hydrogen bonding between lactam functions. Comparison with literature values for
      polyalkyldipyrrin-1-ones shows that, apart from the local constraints of the
      benzene ring, the fused benzo ring has little effect on the molecular dimensions
      of the dipyrrin-1-one skeleton.

PMID- 15579976
TI  - Swertisin dihydrate.
AB  - The title compound, 6-C-glucopyranosyl-7-O-methylapigenin dihydrate,
      C(22)H(22)O(10).2H(2)O, is a natural C-glucosylflavone. The flavone skeleton is
      almost planar, the dihedral angle between the pyran moiety and the 4
      hydroxyphenyl ring being 9.8 (3) degrees. The basal plane of the pyranosyl ring
      of the glucose moiety is almost perpendicular to the benzopyran ring system. The
      flavone skeletons are stacked along the a axis, forming layers parallel to (001).
      Between these hydrophobic layers, the glucose groups and water molecules of
      crystallization are connected via O-H...O hydrogen bonds, forming hydrophilic
      layers.

PMID- 15579977
TI  - X-ray investigations of bicyclic alpha-methylene-delta-valerolactones. II.
      (4aS,8aS)-4a-methyl-3-methyleneperhydrochromen-2-one.
AB  - The title compound, C(11)H(16)O(2), adopts a semifolded conformation with the
      delta-lactone and cyclohexane rings almost perpendicular to one another. The beta
      methyl substituent occupies an axial position with respect to the cyclohexane
      ring. The delta-lactone moiety adopts a slightly distorted half-chair
      arrangement, while the cyclohexane ring exists in an almost ideal chair
      conformation.

PMID- 15579978
TI  - A pimpinellin monomer and dimer isolated from the roots of Esenbeckia
      grandiflora.
AB  - X-ray diffraction studies carried out on single crystals of the monomeric, viz.
      5,6-dimethoxy-2H-furo[2,3-h][1]benzopyran-2-one, C(13)H(10)O(5), and dimeric,
      viz. 5,5',6,6'-tetramethoxy-3,3',4,4'-tetrahydro-2H,2'H-3,3':4,4'-bi(furo[2,3
      h][1]benzopyran)-2,2'-dione, C(26)H(20)O(10), forms of pimpinellin have revealed
      that, following cyclodimerization, the carbonyl groups are head-to-head with
      respect to one another. In the monomer, the heterocyclic ring is planar, but it
      exhibits a twisted-boat conformation in the dimer. Both the monomer and the dimer
      interact through C-H...O interactions.

PMID- 15579979
TI  - Current management of retinoblastoma.

PMID- 15579980
TI  - Update on retinoblastoma.

PMID- 15579981
TI  - Continuing challenges in the management of retinoblastoma with chemotherapy.
AB  - The management of retinoblastoma has gradually changed over the past 10 years.
      Over 95% of children with retinoblastoma in the United States are cured with
      modern techniques. The challenge remains, however, in maintaining the eye and
      vision. There is a trend away from enucleation and external beam radiotherapy
      toward focal conservative treatments involving primary chemoreduction in
      conjunction with thermotherapy and cryotherapy. This is related to earlier
      detection of the disease, recognition of more effective chemotherapeutic agents,
      more focused local treatment modalities, and, most importantly, knowledge of the
      long-term risks of external beam radiotherapy. Enucleation is still preferable
      for retinoblastoma that fills most of the eye, especially when the disease is
      unilateral or when there is concern for tumor invasion into the optic nerve,
      choroid, or orbit. The orbital integrated implant is placed after enucleation and
      provides acceptable prosthesis motility and appearance. External beam
      radiotherapy is still vital for treating advanced retinoblastoma, especially when
      there is diffuse vitreous or subretinal seeding after failure of other methods
      and preservation of vision is a priority. The most important recent advance in
      the management of retinoblastoma is the use of intravenous chemotherapy for tumor
      reduction, a technique of neoadjuvant chemotherapy termed "chemoreduction." This
      is followed by tumor consolidation with focal measures such as thermotherapy,
      cryotherapy, and plaque radiotherapy. This strategy provides reduced tumor volume
      and often permits consolidation with methods other than radiotherapy. It appears
      that vision can be preserved in some cases with these methods, avoiding some of
      the local complications like radiation cataract or macular edema that have been
      found with radiotherapy techniques. External beam radiotherapy and enucleation
      can now be avoided in most cases of Reese-Ellsworth groups I (minimal disease)
      through IV (moderate disease) retinoblastoma. The most advanced stage of
      retinoblastoma, Reese-Ellsworth group V, continues to provide the greatest
      difficulty for management, and external beam radiotherapy and enucleation are
      often employed in addition to chemoreduction to save the child's life. A
      collaborative prospective study in North America is currently under way to
      further study the benefits and risks of chemoreduction for minimal, moderate, and
      advanced retinoblastoma.

PMID- 15579982
TI  - Photodynamic therapy of subfoveal and juxtafoveal choroidal neovascularization in
      ocular histoplasmosis syndrome: a retrospective case series.
AB  - PURPOSE: To evaluate the safety and effect on visual acuity of photodynamic
      therapy (PDT) with verteporfin in patients with subfoveal and juxtafoveal
      choroidal neovascular membranes from ocular histoplasmosis syndrome (OHS).
      METHODS: Retrospective case series. The visual outcome of 11 patients with
      subfoveal (n = 6) and juxtafoveal (n = 5) choroidal neovascularization treated
      with PDT was reviewed. At 1 to 3 months of follow-up, retreatment with PDT was
      performed if angiography showed leakage. RESULTS: Within the subfoveal group, 3
      patients (50%) had improved vision (two or more lines better than initial
      vision), 2 patients (33.3%) had no change in vision (within 1 line), and 1
      (16.7%) lost four lines of vision. At last follow-up, 3 patients (50%) had vision
      between 20/20 and 20/40 compared with only 1 patient (16.6%) at the initial
      visit. Mean follow-up was 13.7 months. Within the juxtafoveal group, 3 patients
      (60%) had improved vision, 1 patient (20%) had no change in vision, and 1 patient
      (20%) lost nine lines of vision. At last follow-up, 3 of 5 patients (60%) had
      vision between 20/20 and 20/40 compared with 2 patients (40%) at the initial
      visit. Mean follow-up was 10.2 months. No significant adverse effects were
      reported. CONCLUSION: PDT is a safe and promising option for patients with OHS
      with choroidal neovascularization that is subfoveal or juxtafoveal.

PMID- 15579983
TI  - Sudden visual loss after removal of silicone oil.
AB  - PURPOSE: Removal of silicone oil after vitreoretinal surgery reduces potential
      complications of glaucoma and cataract and improves visual function in 30% of
      patients. We report the clinical findings of a series of patients who experienced
      unexpected and permanent visual loss after removal of silicone oil. METHODS:
      Seven patients with visual loss after removal of silicon oil were investigated
      with best-corrected Snellen visual acuity (BCVA) assessment, fundus
      biomicroscopy, fluorescein angiography, optical coherence tomography, and
      electrophysiologic examination. RESULTS: Six men and one woman (average age, 42.8
      years.) presented with profound BCVA loss, averaging 4.7 Snellen lines (SD 1.4),
      after silicon oil removal. No other complications associated with oil removal
      were noted. The retina remained attached in all cases, no patient developed
      cystoid macular edema or epiretinal membrane, and optical coherence tomographic
      and fluorescein angiographic findings remained normal. Electrodiagnostic testing
      showed a range of abnormalities, with the majority of patients showing severe
      macular dysfunction. CONCLUSIONS: We describe a new phenomenon of unexpected
      visual loss after oil removal in patients with good visual potential. The
      pathogenesis remains obscure.

PMID- 15579984
TI  - A randomized prospective study of rhegmatogenous retinal detachment cases treated
      with cryopexy versus frequency-doubled Nd:YAG laser-retinopexy during episcleral
      surgery.
AB  - PURPOSE: To evaluate the efficacy of cryopexy versus transpupillary frequency
      doubled (532 nm) Nd:YAG laser-retinopexy according to anatomic and functional
      success and postoperative complications. METHODS: Seven hundred three patients
      with primary rhegmatogenous retinal detachment were enrolled. They underwent
      scleral-buckling surgery using randomly transpupillary frequency-doubled Nd:YAG
      laser or cryotherapy for retinopexy: patients were observed for a period of 6
      months. The primary outcome was anatomic success at 6 months. Secondary outcomes
      included anterior segment complications, posterior segment complications, and
      postoperative visual acuity. RESULTS: There was no significant difference between
      the primary and secondary outcomes in the two treatment groups: the anatomic
      success rate was 83% in the transpupillary frequency-doubled Nd:YAG laser group
      and 83.1% in the cryotherapy group; the rate of postoperative complications and
      the postoperative visual acuity results are also similar in the two groups; the
      only barely statistically significant difference (P = 0.045) was the rate of
      macular holes, which were present only in five myopic patients treated with
      transscleral cryopexy. CONCLUSION: Transpupillary frequency-doubled Nd:YAG laser
      retinopexy, as cryopexy, served as a safe and effective means of creating
      chorioretinal adhesion during retinal reattachment surgery. The rate of
      postoperative complications was not influenced by the type of retinopexy.

PMID- 15579985
TI  - Resources involved in managing retinal detachment complicated by proliferative
      vitreoretinopathy.
AB  - PURPOSE: To report the differences in cost of treatment and outcome in retinal
      detachment (RD) cases with and without proliferative vitreoretinopathy (PVR).
      METHODS: Analysis of clinical trial databases of RD observed in 190 eyes of 190
      patients. Eyes were classified as no PVR, developing PVR, or established PVR. For
      each eye, total cost of treatment undertaken on Moorfields Eye Hospital
      vitreoretinal unit, final retinal status, and best-corrected visual acuity were
      recorded. RESULTS: Management of patients who developed PVR involved
      approximately double the resources of RD without PVR. Eyes with pre-exiting PVR
      had similar resource input to those with RD without PVR. Patients who developed
      PVR had a mean of 3.7 operations (including subsequent cataract surgery) compared
      to 1.8 and 2.1 respectively for noncomplicated RD and pre-existing PVR. Anatomic
      success and visual outcome was significantly worse in eyes with PVR. CONCLUSIONS:
      Treatment of eyes that developed PVR after initial surgery cost significantly
      more than eyes with no PVR or established PVR (P < 0.01). Improvements in the
      management of RD aimed at preventing PVR and advances in PVR treatment may have
      significant financial as well as clinical benefits.

PMID- 15579987
TI  - Intravitreal concentration and clearance of triamcinolone acetonide in
      nonvitrectomized human eyes.
AB  - PURPOSE: To determine the intravitreal concentration and clearance of
      triamcinolone acetonide at various intervals after intravitreal injection into
      nonvitrectomized eyes. METHODS: Six participants were administered 4 mg (0.1 cc)
      of triamcinolone acetonide ophthalmic suspension. All six eyes underwent
      therapeutic pars plana vitrectomy with membranectomy at various post injection
      intervals ranging from 1.25 to 5 months from the intravitreal injection.
      Undiluted specimens of vitreous overlying the macula and of aqueous humor were
      submitted for analysis. Vitreous and aqueous humor concentrations of
      triamcinolone were measured by high performance liquid chromatography. RESULTS:
      Four eyes demonstrated detectable intravitreal concentrations of triamcinolone
      acetonide between 1.25 and 2.75 months after a single injection. Two eyes had an
      undetectable level of triamcinolone in both the vitreous and aqueous at 3 and 5
      months post single injection. CONCLUSIONS: The intravitreal concentration of
      triamcinolone acetonide is detectable up to 2.75 months post a single 4 mg
      injection in nonvitrectomized eyes. A reinjection interval of 3 months may be
      needed to achieve sustained measurable levels of triamcinolone in
      nonvitrectomized patients.

PMID- 15579986
TI  - Changes in lesion size after submacular surgery for subfoveal choroidal
      neovascularization in the submacular surgery trials pilot study.
AB  - PURPOSE: To compare the size of subfoveal lesions based on photographic
      documentation before and after submacular surgery of choroidal neovascularization
      (CNV) lesions. METHODS: Subfoveal lesion sizes at baseline and month 3 follow-up
      visits for patients assigned to surgery in the Submacular Surgery Trials (SST)
      Pilot Study were assessed categorically using Macular Photocoagulation Study
      (MPS) disc area (DA) circles. The Submacular Surgery Trials Pilot Study groups
      reviewed were as follows: Group N (age-related macular degeneration [AMD]; lesion
      <50% blood; classic CNV present; size < or =9 MPS DAs); Group R (AMD; prior
      nonfoveal laser; classic CNV present; size < or =9 MPS DAs); Group B (AMD; lesion
      > or =50% blood); and Group H (ocular histoplasmosis syndrome or idiopathic;
      classic CNV present; size < or =9 MPS DAs). RESULTS: Postoperative month 3 lesion
      size was at least 1 size category smaller than the preoperative lesion size in 6%
      (4/66) of Group N, 0 (0/31) of Group R, 6% (2/34) of Group H, and 45% (18/40) of
      Group B eyes. In Group H eyes, there was no size change in 50% (17/34), and
      enlargement was found in 44% (15/34). For eyes in Groups N and R, approximately
      one third remained stable (20/66, 30% and 12/31, 39%, respectively), whereas two
      thirds enlarged by at least 1 category (42/66, 64% and 19/31, 61%, respectively).
      CONCLUSIONS: The change in lesion size after submacular surgery was variable,
      with a tendency for Group H lesions to remain the same size or larger, Group B
      lesions to measure smaller, and Group N and Group R lesions to be larger.

PMID- 15579988
TI  - Retrobulbar injection of methylprednisolone in diffuse diabetic macular edema.
AB  - PURPOSE: To study some aspects of locally and extraocularly administered
      methylprednisolone on diffuse diabetic macular edema. METHODS: The investigation
      included 13 eyes of 13 diabetic subjects. One eye received treatment, and the
      other eye served as control. Standardized visual acuity as well as the presence
      of clinically significant macular edema was recorded before and several times
      after retrobulbar injection of methylprednisolone. The follow-up period was at
      least 6 months. RESULTS: One month after retrobulbar injection of
      methylprednisolone, visual acuity increased significantly (before, 0.19; after,
      0.30). Visual acuity was also significantly increased 3 and 6 months after this
      treatment (before, 0.19; 3 months after, 0.26; 6 months after, 0.28). The
      proportion of eyes with diffuse clinically significant macular edema was
      gradually reduced from 100% before treatment to 15% 6 months after treatment.
      CONCLUSION: Retrobulbar injection of methylprednisolone increased visual acuity
      significantly in diabetic subjects with diffuse macular edema. A significant
      reduction in the number of eyes with clinically significant macular edema was
      also observed.

PMID- 15579990
TI  - Choroidal vascular occlusion in internal carotid artery obstruction.
AB  - PURPOSE: To determine choroidal vascular abnormalities in eyes with internal
      carotid artery obstruction (ICO). METHODS: We examined eight eyes with ICO with
      wide-angle indocyanine green (ICG) video-angiography beginning in the posterior
      fundus. Another angiography was performed in three eyes to observe the arterial
      phase of the temporal peripheral fundus. ICG angiography was done until the late
      choroidal venous phase or for more than 10 minutes. RESULTS: Slow dye filling in
      the choroidal arteries and delayed filling of the posterior watershed zone
      occurred in all eyes. Delayed perfusion or multiple patchy occlusions of
      choriocapillaris was seen in all eyes. There were delayed perfusion and/or
      occlusion in the peripheral watershed zone in the examined three eyes. The super
      late-phase angiograms showed hyperfluorescent lines corresponding to choroidal
      veins. CONCLUSION: Elongated arm-to-choroid circulation and delayed
      intrachoroidal circulation times suggest severe choroidal hypoperfusion.
      Choroidal hypoperfusion resulted in multiple occlusions of the choriocapillaris
      and attenuated choroidal vessels. Slow filling or nonperfusion of the peripheral
      watershed zone was another characteristic finding. Linear hyperfluorescence may
      reflect severely damaged choroidal venous walls. These findings are useful to
      understand choroidal angiopathy in ICO or high-grade stenosis, and to diagnose
      ocular ischemic syndrome.

PMID- 15579989
TI  - Correlation of optical coherence tomography with angiography in retinal pigment
      epithelial detachment associated with age-related macular degeneration.
AB  - PURPOSE: To correlate optical coherence tomography (OCT) with angiographic signs
      of choroidal neovascularization (CNV) in retinal pigment epithelial detachment
      (PED) associated with age-related macular degeneration (ARMD). METHODS:
      Prospectively, the authors performed OCT in 35 eyes of 35 patients (30 men and 5
      women with a mean age of 71.6 years [range, 56-76 years]) with ARMD. All 35 eyes
      had CNV in the area of PED or adjacent to it, which was shown by fluorescein or
      indocyanine green angiography. Cross-sectional images were obtained by the OCT
      scanning line through the CNV and PED. RESULTS: In 10 (56%) of 18 eyes in which
      the CNV was at the margin of the PED, a small PED was adjacent to the central,
      dome-shaped PED. There was a notch between the central and small mounds of PED.
      In 13 (76%) of 17 eyes in which the CNV was within the PED, a notch was seen in
      the dome-shaped PED, resulting in a contour with 2 mounds. One of the 2 mounds
      contained a highly reflective mass immediately beneath the detached retinal
      pigment epithelium in 8 (62%) of the 13 eyes. CONCLUSION: A tomographic notch in
      the PED may be diagnostically important as an indication of CNV beneath the
      detached retinal pigment epithelium in eyes with ARMD.

PMID- 15579991
TI  - Electroretinographic findings in patients with Stargardt disease and fundus
      flavimaculatus.
AB  - PURPOSE: To characterize the clinical and electroretinogram (ERG) features of our
      cohort of patients with Stargardt disease (STGD) exhibiting coding sequence
      variations in the ABCA4 gene. METHODS: Review of 76 patients with the clinical
      diagnosis of Stargardt disease/fundus flavimaculatus (STGD/FF) from the
      University of Iowa Department of Ophthalmology and Visual Sciences (41 patients)
      and the Casey Eye Institute (35 patients). Clinical examination, Goldmann
      perimetry, and electroretinography were performed on all 76 patients. Patients
      were divided into three groups on the basis of their funduscopic and
      electroretinographic features: (1) a normal ERG by the standards of the
      laboratory; (2) minimal rod or cone abnormalities; (3) severe ERG dysfunction.
      The latter category was further subdivided on the basis of a cone-dominated loss
      of function (C > R or "cone-rod dystrophy") or diffuse depression of rods and
      cones (C = R). Mutational analysis of the coding sequence of the ABCA4 gene was
      performed by single strand conformation polymorphism analysis followed by
      automated DNA sequencing. Each electroretinographic group was analyzed for the
      presence of disease causing changes using exact tests of binomial proportions
      corrected for multiple comparisons by Bonferroni method. Quantitative polymerase
      chain reaction (QPCR) was performed on patients who were homozygous for disease
      causing changes in the ABCA4 gene to rule out the possibility of deletions.
      RESULTS: Overall, 56 of 76 patients (and 77 of 152 alleles) exhibited coding
      sequence variations that were compatible with high-penetrance disease-causing
      mutations. The most common of these were His423Arg (9), frameshift mutations (7),
      Ala1038Val (7), and Pro1380Leu (6). Although no patients with His423Arg presented
      with normal ERGs, no significant correlation was observed between specific
      sequence variations and the electroretinographic characteristics or fundus
      appearance. However, a significantly greater fraction of patients with normal ERG
      studies failed to exhibit detectable disease-causing coding sequence variations
      in the ABCA4 gene identified on either allele (P = 0.0006). CONCLUSION: STGD/FF
      patients in our cohort exhibit a wide range of electroretinographic
      abnormalities, some of which are more prevalent than previously suspected. No
      direct correlation between clinical appearance, electrophysiologic
      characteristics and specific ABCA4 alleles could be identified, although a
      significantly lower number of our cohort with a normal ERG exhibited detectable
      coding sequence variations in the ABCA4 gene. However, four patients with ERG
      dysfunction were homozygous for a His423Arg change proven by QPCR not to be an
      artifact of a deletion. The presence of electrophysiologic dysfunction is not
      uncommon in our cohort of patients with STGD. Thus, the ERG provides clinically
      important information of retinal function for STGD/FF and, as such, is still
      indicated as part of the evaluation of these patients.

PMID- 15579993
TI  - Clinical features of Japanese families with a 402delT or a 555-556delAG mutation
      in choroideremia gene.
AB  - PURPOSE: To characterize the clinical features of two Japanese families with
      choroideremia associated with a 402delT and a 555-556delAG mutation in the
      choroideremia gene (CHM). METHODS: Four affected members and one obligate carrier
      from two Japanese families with choroideremia were studied. To detect mutations
      of the CHM gene, the products of polymerase chain reaction were directly
      sequenced in both directions. The ophthalmologic examination included best
      corrected visual acuity, slit-lamp examination, fundus examination, kinetic
      perimetry, electroretinography, and fluorescein angiography. RESULTS: A 402delT
      and a 555-556delAG mutation were found in two Japanese families with
      choroideremia. All affected members had night-blindness, progressive constriction
      of the visual field, chorioretinal atrophy, and mottled appearance of the retinal
      pigment epithelium. The obligate carrier had mild patchy areas of retinal pigment
      epithelial atrophy with no visual symptoms. CONCLUSION: The authors found a
      402delT and a 555-556delAG mutation in the CHM gene, one of which (402delT) is a
      novel mutation. They conclude that these mutations cause choroideremia in
      Japanese families.

PMID- 15579992
TI  - Morphology and functional characteristics in adult vitelliform macular dystrophy.
AB  - PURPOSE: Detailed morphologic and functional evaluation of adult vitelliform
      macular dystrophy (AVMD). METHODS: The records of 61 consecutive AVMD patients
      (inclusion criterion: vitelliform lesion smaller than one disk diameter at least
      in one eye) were evaluated retrospectively regarding visual acuity, color vision,
      perimetry, retinal pigment epithelium (RPE) autofluorescence, fluorescein
      angiography, electro-oculography, full-field and multifocal electroretinography,
      and molecular genetic evaluation of the VMD2 and RDS/peripherin genes. RESULTS:
      The mean age of subjects was 54.6 years. Visual loss was variable (median, 0.6;
      range, 1.25-0.05). Color vision and visual field were normal in about half of the
      patients but presented defects with high variability in the remaining patients.
      Autofluorescence findings showed increased fluorescence within the foveal yellow
      lesion in 76%. In the majority of eyes, the amplitude of the 30 Hz flicker
      response of the full-field electroretinogram (72%) and the central P1 amplitude
      of the multifocal electroretinogram (63%) were reduced. Mutational analyses
      revealed a potentially disease-associated mutation in the RDS/peripherin gene in
      one patient. CONCLUSION: AVMD is characterized by late onset, slow progression,
      good prognosis, and high variability of morphologic and functional abnormalities
      resulting frequently in misdiagnosis. Autofluorescence findings indicate
      lipofuscin accumulation in the yellow lesion. Electroretinography revealed a
      generalized cone system dysfunction with increasing severity toward the fovea.

PMID- 15579995
TI  - Retinal detachment in atopic dermatitis can masquerade as acute panuveitis with
      rapidly progressive cataract.
AB  - PURPOSE: To report two cases of retinal detachment in young patients with atopic
      dermatitis masquerading as acute panuveitis. DESIGN: Retrospective observational
      clinical case reports. PATIENTS: Patients with atopic dermatitis presenting with
      acute panuveitis and subsequently diagnosed with retinal detachment at the
      Singapore National Eye Centre. METHODS: A review of the clinical case records.
      RESULTS: Two young patients aged 19 and 21 years with a history of atopic
      dermatitis presented with acute unilateral moderately severe panuveitis. Both
      developed rapidly progressing cataracts that made detailed visualization of the
      fundus difficult. Hypotony persisted in one eye despite partial response of
      uveitis to therapy. The other patient developed ocular hypertension when the
      vision in the affected eye suddenly deteriorated. Both eyes demonstrated partial
      response to steroid therapy. The diagnosis of shallow retinal detachment with
      anteriorly located incriminating retinal breaks was made after partial resolution
      of vitreous haze in one case and on repeated ultrasonography in the other case.
      CONCLUSION: A high index of suspicion is required when examining young patients
      with atopic dermatitis who present with acute panuveitis and a rapidly
      progressive cataract, which may mask the presence of a shallow retinal
      detachment.

PMID- 15579994
TI  - Ocular fundus images by scanning laser ophthalmoscopy in a patient with enhanced
      S-cone syndrome.
AB  - PURPOSE: To present ocular fundus images in a patient with enhanced S-cone
      syndrome by scanning laser ophthalmoscopy. A 34-year-old Japanese woman whose
      parents were consanguineous showed mismatched electroretinographic responses to
      photopically balanced single-flash stimuli, with a larger signal to blue light
      than to red light. The central macula lacked a foveal reflex, and the surface was
      dull. Yellowish flecks and retinal pigment epithelium atrophy were evident in a
      ring at and around the vascular arcades. Faint black pigmentation was deposited
      in the mid peripheral retina. METHODS: The ocular fundus of the patient was
      observed by scanning laser ophthalmoscopy with the use of an argon blue laser
      (wavelength, 488 nm), a helium-neon laser (633 nm), and an infrared laser (780
      nm). RESULTS: The argon blue laser showed numerous black spots of pigment, which
      were observed as faint pigmentation by conventional ophthalmoscopy. The spots
      were more enhanced with the argon blue laser than with the helium-neon laser. The
      white spots, which corresponded to the yellowish flecks in a ring at and around
      the vascular arcades, were more enhanced with the helium-neon laser than with the
      argon blue or infrared laser. Hypopigmentation of the retinal pigment epithelium
      was best shown with the infrared laser. CONCLUSION: An abnormality of the retinal
      structure in enhanced S-cone syndrome may exist in the inner and outer retinal
      levels, in at least some patients.

PMID- 15579996
TI  - Diagnostic and therapeutic challenges.

PMID- 15579997
TI  - Treatment of retinal detachment after macular translocation with scleral
      infolding: preservation of macular translocation.

PMID- 15579998
TI  - Trans-tenon retrobulbar triamcinolone infusion for chronic macular edema in
      central and branch retinal vein occlusion.

PMID- 15579999
TI  - Biomechanical characteristics of retina.

PMID- 15580000
TI  - Noninvasive evaluation for retinal pigment epithelium hamartoma.

PMID- 15580001
TI  - Childhood optic neuritis associated with premacular epiretinal membrane.

PMID- 15580002
TI  - Retinal oxalosis in primary hyperoxaluria type 1.

PMID- 15580003
TI  - Gyrate atrophy associated with astrocytic hamartoma of the optic disc.

PMID- 15580004
TI  - Symmetrical reduced retinal thickness in a patient with Alport syndrome.

PMID- 15580005
TI  - Central retinal artery occlusion secondary to spontaneous internal carotid artery
      dissection.

PMID- 15580006
TI  - Retinal capillary hemangioma managed by transpupillary thermotherapy.

PMID- 15580007
TI  - Macroaneurysm on the optic disk associated with congenital retinal arterial
      malformation.

PMID- 15580008
TI  - Silicone oil pupil-block acute angle-closure glaucoma: optimal laser position.

PMID- 15580012
TI  - WTA presidential address: The man in the glass.

PMID- 15580009
TI  - Indocyanine green angiography-guided photodynamic therapy for treatment of
      chronic central serous chorioretinopathy: a pilot study.

PMID- 15580013
TI  - Secondary ultrasound examination increases the sensitivity of the FAST exam in
      blunt trauma.
AB  - INTRODUCTION: Approximately one third of stable patients with significant intra
      abdominal injury do not have significant intraperitoneal blood evident on
      admission. We hypothesized that a delayed, repeat ultrasound study (Secondary
      Ultrasound--SUS) will reveal additional intra-abdominal injuries and
      hemoperitoneum. METHODS: We performed a prospective observational study of trauma
      patients at our Level I trauma center from April 2003 to December 2003. Patients
      underwent an initial ultrasound (US), followed by a SUS examination within 24
      hours of admission. Patients not eligible for a SUS because of early discharge,
      operative intervention or death were excluded. All US and SUS exams were
      performed and evaluated by surgical/emergency medicine house staff or surgical
      attendings. RESULTS: Five hundred forty-seven patients had both an initial US and
      a SUS examination. The sensitivity of the initial US in this patient population
      was 31.1% and increased to 72.1% on SUS (p < 0.001) for intra-abdominal injury or
      intra-abdominal fluid. The specificity for the initial US was 99.8% and 99.8% for
      SUS. The negative predictive value was 92.0% for the initial US and increased to
      96.6% for SUS (p = 0.002). The accuracy of the initial ultrasound was 92.1% and
      increased to 96.7% on the SUS (p < 0.002). No patient with a negative SUS after 4
      hours developed clinically significant hemoperitoneum. CONCLUSION: A secondary
      ultrasound of the abdomen significantly increases the sensitivity of ultrasound
      to detect intra-abdominal injury.

PMID- 15580014
TI  - Does routine serial computed tomography of the head influence management of
      traumatic brain injury? A prospective evaluation.
AB  - BACKGROUND: Computed tomography (CT) of the head is the current standard for
      diagnosing intracranial pathology following blunt head trauma. It is common
      practice to repeat the head CT to evaluate any progression of injury. Recent
      retrospective reviews have challenged the need for serial head CT after traumatic
      brain injury (TBI). This study intends to prospectively examine the value of
      routine serial head CT after TBI. METHODS: Consecutive adult blunt trauma
      patients with an abnormal head CT admitted to an urban, Level I trauma center
      from January 2003 to September 2003 were prospectively studied. Variables
      collected included: initial head CT results, indication for repeat head CT
      (routine versus neurologic change), number and results of repeat head CT scans,
      and clinical interventions following repeat head CT. RESULTS: Over the 9-month
      period, there were 128 patients admitted with an abnormal head CT after
      sustaining blunt trauma. The 16 patients who died within 24 hours and the 12
      patients who went directly to craniotomy were excluded. The remaining 100
      patients make up the study population. Abnormal head CT findings were
      subarachnoid hemorrhage (47%), intraparenchymal hemorrhage (37%), subdural
      hematoma (28%), contusion (14%), epidural hematoma (11%), intraventricular
      hemorrhage (3%), and diffuse axonal injury (2%). Overall, 32 patients (32%) had
      only the admission head CT, while 68 patients (68%) underwent 90 repeat CT scans.
      Of the repeat head CT scans, 81 (90%) were performed on a routine basis without
      neurologic change. The remaining 9 (10%) were performed for a change in Glasgow
      Coma Scale (n = 5), change in intracranial pressure (n = 1), change in Glasgow
      Coma Scale and intracranial pressure (n = 1), change in pupil size (n = 1), or
      sudden appearance of a headache (n = 1). Three patients had their care altered
      after repeat head CT: two underwent craniotomy and one was started on barbiturate
      therapy. All three patients had their repeat head CT after neurologic change
      (decrease in Glasgow Coma Scale in 2 and increase in intracranial pressure in 1).
      CONCLUSIONS: Serial head CT is common after TBI. Most repeat head CT scans are
      performed on a routine basis without neurologic change. Few patients with TBI
      have their management altered after repeat head CT, and these patients have
      neurologic deterioration before the repeat head CT. The use of routine serial
      head CT in patients without neurologic deterioration is not supported by the
      findings of this study.

PMID- 15580016
TI  - Systemic neutrophil priming by lipid mediators in post-shock mesenteric lymph
      exists across species.
AB  - BACKGROUND: Post-hemorrhagic shock mesenteric lymph (PHSML) has been linked with
      neutrophil (PMN) priming, endothelial cell (EC) activation, and acute lung injury
      (ALI) in rodent models. We have previously identified the lipid fraction of PHSML
      as containing the causative agent(s). Due to the lesson learned from the rodent
      gut bacterial translocation experience, we sought to confirm this phenomenon
      using a large animal model; hypothesizing that lymph collected from the porcine
      gut following ischemia/reperfusion (I/R) would cause PMN priming. METHODS:
      Mesenteric lymph was collected from adult pigs before, during, and for 2 hours
      after non-lethal hemorrhagic shock (mean arterial pressure = 30 mm Hg x 45
      minutes). Whole lymph and the extracted lipid fractions of the lymph were then
      added to isolated human and porcine PMNs and superoxide production was measured
      by cytochrome C reduction. RESULTS: Hemorrhagic shock profoundly affected
      mesenteric lymph flow from baseline (pre-shock) flow rates of 75.63 +/- 8.86
      mL/hr to 49.38 +/- 5.76 mL/hr during shock and increasing to 253.38 +/- 27.62
      mL/hr after 2 hours of resuscitation. Human PMNs exposed to both whole lymph
      (PHSML) and its extracted lipids (PHSML Lipid) collected 2 hours after shock
      exhibited more than a two-fold increase in superoxide release upon activation
      compared with pre-shock samples: PHSML- 6.27 +/- 0.83 versus 2.56 +/- 0.60
      nmolO2(-)/ 3.75 cells/mL/min, respectively (p = 0.007), PHSML Lipid- 4.93 +/-
      0.34 versus 2.49 +/- 0.11 nmolO2(-)/ 3.75 cells/mL/min (p < 0.001). Similarly,
      porcine PMNs exhibited close to a two-fold activation when exposed to the lymph
      and lipid fraction: PHSML- 4.51 +/- 0.42 versus 1.06 +/- 0.28 nmolO2(-)/ 3.75
      cells/mL/min (p = 0.008), PHSML Lipid-4.80 +/- 0.81 versus 1.55 +/- 0.23 nmolO2(
      )/ 3.75 cells/mL/min (p = 0.002). CONCLUSION: Mesenteric lymphatics serve as the
      conduit for inflammatory mediators elaborated by the post-ischemic gut in both
      small and large animal models. Further, the causal agent(s) exist in the lipid
      fraction of the lymph and are active on both human and animal PMNs.

PMID- 15580015
TI  - Non-helmeted motorcyclists: a burden to society? A study using the National
      Trauma Data Bank.
AB  - INTRODUCTION: Helmet laws remain controversial. Opponents believe negative
      findings are a result of biased statistical analyses that fail to account for the
      impact of alcohol and drugs. In this study, we evaluated the effect that helmet
      use had upon injury severity, outcome controlling for alcohol or drug use,
      resource utilization, and financial burden using the National Trauma Data Bank
      (NTDB). METHODS: Two groups of patients, helmeted and non-helmeted motorcyclists,
      were identified using the NTDB over an 8-year period. Group differences were
      compared using nonparametric Wilcoxon tests for continuous variables and Fisher's
      exact test for dichotomous outcomes. To evaluate the effect that alcohol or drug
      use had on mortality, logistic regression models were created. RESULTS: A total
      of 9,769 patients were identified by the NTDB of which 6756 (69.2%) were helmeted
      and 3013 (30.8%) were non-helmeted. Helmet use was associated with lower injury
      severity, mortality, and resource utilization. Non-helmeted motorcyclists accrued
      greater hospital charges and were significantly less likely to have health
      insurance. When controlling for alcohol or drug use, mortality continued to be
      significantly associated with non-helmet use. CONCLUSION: Non-helmeted
      motorcyclists have worse outcomes than their helmeted counterparts independent of
      the use of alcohol or drugs. Furthermore, they monopolize more hospital
      resources, incur higher hospital charges, and as non-helmeted motorcyclists
      frequently do not have insurance, reimbursement in this group of patients is
      poor. Thus, the burden of caring for these patients is transmitted to society as
      a whole.

PMID- 15580017
TI  - Attenuation of shock-induced acute lung injury by sphingosine kinase inhibition.
AB  - BACKGROUND: Prolonged elevations of cytosolic calcium concentrations ([Ca2+]i)
      are required for optimal neutrophil (PMN) activation responses to G-Protein
      coupled chemoattractants. We recently showed that the coupling of endosomal Ca2+
      store depletion to more prolonged entry of external Ca2+ depends on cellular
      conversion of sphingosine to sphingosine 1-phosphate (S1P) by sphingosine kinase
      (SK). We therefore hypothesized that inhibition of SK might inhibit PMN
      activation and thus ameliorate lung injury after trauma and hemorrhagic shock
      (T/HS). METHODS: Chemotaxis (CTX) of human PMN was studied using modified Boyden
      chambers in the presence or absence of the selective SK inhibitor, SKI-2. After
      determining the concentration of SKI-2 that inhibited human PMN CTX by 50% (IC50)
      we subjected rats to T/HS (laparotomy, hemorrhage to 30-40 mm Hg x 90 minutes, 3
      hours resuscitation). We then studied rat PMN CD11b expression using flow
      cytometry and lung injury using the Evans Blue dye technique in the presence of
      IC50 doses of SKI-2 or vehicle given in pretreatment at laparotomy. RESULTS:
      Human PMN CTX was suppressed slightly more than 50% by 40 micromol/L SKI-2 (233
      +/- 20 vs 103 +/- 12 x 10(3) cells/well, p < 0.001). Rat PMN expression of CD11b
      after T/HS was decreased from 352 +/- 30 to 232 +/- 7 MFU (p < 0.001) in the
      presence 30 micromol/L SKI-2. Lung permeability to Evans Blue was decreased from
      9.5 +/- 2 to 4.1 +/- 0.7% (p = 0.036.). SKI-2 did not cause hemodynamic
      instability or alter resuscitation requirements. CONCLUSION: Modulation of PMN Ca
      entry via SK inhibition inhibits PMN CTX in vitro, and inhibits CD11b expression
      in vivo without major effects on hemodynamics. These cellular changes were
      associated with amelioration of lung injury in vivo in a rat model of T/HS. These
      findings suggest that SK inhibition allows modulation of inflammation via control
      of [Ca2+]i without the cardiovascular compromise expected with Ca2+ channel
      blockade. SK inhibition therefore appears to be an important novel candidate
      therapy for inflammatory organ injury after shock.

PMID- 15580018
TI  - The rate of induction of hypothermic arrest determines the outcome in a Swine
      model of lethal hemorrhage.
AB  - BACKGROUND: Lethal injuries can be surgically repaired under asanguineous
      hypothermic condition (suspended animation) with excellent outcome. However, the
      optimal rate for the induction of hypothermic metabolic arrest following
      uncontrolled lethal hemorrhage (ULH) is unknown. METHODS: ULH was induced in 32
      female swine (80-120 lbs) by creating an iliac artery and vein injury, followed
      30 minutes later by laceration of the descending thoracic aorta. Through a left
      thoracotomy approach, total body hypothermic hyperkalemic metabolic arrest was
      induced by infusing organ preservation fluids into the aorta. Experimental groups
      were: normothermic controls (no cooling, NC), or hypothermia induced at a rate of
      0.5 degrees C/min (slow, SC), 1 degrees C/min (medium, MC), or 2 degrees C/min
      (fast, FC). Vascular injuries were repaired during the 60 minutes of profound (10
      degrees C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid
      exchange, and blood was infused for resuscitation during the re-warming (0.5
      degrees C/ minute) period. The survivors were monitored for 6 weeks. RESULTS: The
      6 week survival rates were 0% (NC), 37.5% (SC), 62.5% (MC), and 87.5% (FC)
      respectively (p < 0.05 MC&FC versus NC). All of the surviving hypothermic arrest
      animals were neurologically intact and displayed no long term organ dysfunction.
      CONCLUSION: Hypothermic metabolic arrest can be used to maintain viability of key
      organs during repair of lethal injuries. Survival is influenced by the rate of
      cooling with the best outcome following rapid induction of hypothermia.

PMID- 15580019
TI  - Interleukin-6 infusion blunts proinflammatory cytokine production without causing
      systematic toxicity in a swine model of uncontrolled hemorrhagic shock.
AB  - BACKGROUND: Serum elevations of interleukin-6 (IL-6) correlate with multiple
      organ dysfunction syndrome and mortality in critically injured trauma patients.
      Data from rodent models of controlled hemorrhage suggest that recombinant IL-6
      (rIL-6) infusion protects tissue at risk for ischemia-reperfusion injury.
      Exogenous rIL-6 administered during shock appears to abrogate inflammation,
      providing a protective rather than a deleterious influence. In an examination of
      this paradox, the current study aimed to determine whether rIL-6 decreases
      inflammation in a clinically relevant large animal model of uncontrolled
      hemorrhagic shock, (UHS), and to investigate the mechanism of protection.
      METHODS: Swine were randomized to four groups (8 animals in each): (1) sacrifice,
      (2) sham (splenectomy followed by hemodilution and cooling to 33 degrees C), (3)
      rIL-6 infusion (sham plus UHS using grade 5 liver injury with packing and
      resuscitation plus blinded infusion of rIL-6 [10 mcg/kg]), and (4) placebo (UHS
      plus blinded vehicle). After 4 hours, blood was sampled, estimated blood loss
      determined, animals sacrificed, and lung harvested for RNA isolation.
      Quantitative reverse transcriptase-polymerase chain reaction was used to assess
      granulocyte colony-stimulating factor (G-CSF), IL-6, and tumor necrosis factor
      alpha (TNFalpha) messenger ribonucleic acid (mRNA) levels. Serum levels of IL-6
      and TNFalpha were measured by enzyme-linked immunoassay (ELISA). RESULTS: As
      compared with placebo, IL-6 infusion in UHS did not increase estimated blood loss
      or white blood cell counts, nor decrease hematocrit or platelet levels. As
      compared with the sham condition, lung G-CSF mRNA production in UHS plus placebo
      increased eightfold (*p < 0.05). In contrast, rIL-6 infusion plus UHS blunted G
      CSF mRNA levels, which were not significantly higher than sham levels (p = 0.1).
      Infusion of rIL-6 did not significantly affect endogenous production of either
      lung IL-6 or mRNA. As determined by ELISA, rIL-6 infusion did not increase final
      serum levels of IL-6 or TNFalpha over those of sham and placebo conditions.
      CONCLUSIONS: Exogenous rIL-6 blunts lung mRNA levels of the proinflammatory
      cytokine G-CSF. The administration of rIL-6 does not increase the local
      expression of IL-6 nor TNFalpha mRNA in the lung. Additionally, rIL-6 infusion
      does not appear to cause systemic toxicity.

PMID- 15580020
TI  - Exogenous nitric oxide donor and related compounds protect against lung
      inflammatory response after hemorrhagic shock and resuscitation.
AB  - BACKGROUND: Resuscitation from hemorrhagic shock triggers an inflammatory
      response characterized by upregulation of cytokine and adhesion molecule
      expression, increased leukocyte activity, and accumulation of polymorphonuclear
      neutrophils in a variety of tissues. This study investigated the capability of an
      exogenous nitric oxide (NO) donor, sodium nitroprusside (NP); a NO substrate, L
      arginine; and an inducible NO synthase inhibitor, L-N6-(1-iminoethyl)lysine (L
      NIL) to reduce lung injury in an animal model of mixed controlled and
      uncontrolled hemorrhagic shock. METHODS: For this study, 72 Sprague-Dawley rats
      weighing 250 to 300 g were subjected to a model of uncontrolled hemorrhagic shock
      for 150 minutes. Six groups of animals were included in this study (12 per
      group): sham-saline, sham-NP, shock-saline, shock-NP, shock-L-arginine, and shock
      L-N6-(1-iminoethyl)lysine. After the period of hemorrhagic shock, resuscitation
      of the groups was accomplished using normal saline (groups 1 and 3), NP (0.5
      mg/kg) (groups 2 and 4), L-arginine (300 mg/kg) (group 5), or L-NIL (50 mg/kg)
      (group 6). The following indices were evaluated: fluid requirements for
      resuscitation, mean arterial pressure (MAP), arterial po2, pco2, and pH, lung wet
      to-dry weight ratio, lung histology and cytokine (interleukin [IL]-1 alpha, IL
      beta 1, tumor necrosis factor-beta [TNF beta], IL-3, IL-4, IL-5, IL-6, IL-10, TNF
      alpha, IL-2, interferon-gamma [IFN gamma]), and mRNA expression in the lung by a
      ribonuclease protection assay (RPA). RESULTS: Sodium nitroprusside significantly
      increased MAP and reduced fluid requirements during resuscitation after
      hemorrhage. There also was a significant improvement in lung function, as
      expressed by improvements in po2, pco2, and pH, and reduction of the wet-to-dry
      weight ratio. In addition, a significant reduction in acute lung injury was
      observed in the histologic studies. Furthermore, the expression of cytokines was
      reduced by NP treatment. The use of L-arginine and L-NIL offered similar
      protective results for the injured lung. CONCLUSIONS: These data suggest that
      limiting inducible NO synthase-generated NO availability with the exogenous NO
      donor, sodium nitroprusside, may reduce lung injury after severe hemorrhage,
      possibly, among other effects, by downregulating the expression of inflammatory
      cytokines. L-arginine and L-NIL also had a beneficial effect on lung function and
      structure.

PMID- 15580021
TI  - The natural history of untreated penetrating diaphragm injury: an animal model.
AB  - BACKGROUND: Surgical repair of diaphragm injuries is rather straightforward, but
      diagnosis can be difficult. The natural history of diaphragm injury is quite
      controversial. Undoubtedly, many diaphragmatic injuries are missed at the initial
      evaluation. Some theories state that diaphragm injuries do not heal, and that all
      eventually lead to herniation. Current theories regarding uniform herniation of
      all diaphragm injuries are not supported by animal models. The authors developed
      a penetrating diaphragm injury model to study the natural history of this injury.
      METHODS: This study used 48 male Sprague-Dawley rats weighing 300-425 g. During
      the study, 24 of the rats received a 16-gauge needle puncture of the left
      diaphragm mimicking a small penetrating wound, whereas 24 of the rats received an
      injury produced with a 2.7-mm aortic punch, which created a defect comparable to
      a much larger penetrating wound. Half of the animals in each group were
      euthanized at 1 month, and the other half at 10 months. This allowed short- and
      long-term follow-up of the injuries. Gross inspection of the left diaphragm was
      performed after the animals were sacrificed via a thoracoabdominal incision. All
      diaphragms then were removed for examination. RESULTS: All the rats experienced
      perioperative recovery. None of the 24 rats with a 16-gauge needle injury had an
      injury at 1 month (n = 12) or 10 months (n = 12). No patent injury was noted in
      the aortic punch injury group (n = 12) sacrificed at 1 month. At 10 months, 1 of
      12 animals had a small hepatic herniation through the aortic punch injury. All
      the injuries displayed adhesions to the underlying left hepatic lobe.
      CONCLUSIONS: The authors developed a penetrating diaphragm injury model to
      understand better the natural history of this injury. Spontaneous healing
      occurred in 98% of the animals. In this animal model, because the left lobe of
      the liver is present beneath the left diaphragm, healing without herniation
      usually occurs. A role may exist for nonoperative treatment of human right
      diaphragm injuries in clinical practice. This animal model may prove useful in
      further defining future management for these injuries.

PMID- 15580022
TI  - Uncompensated metabolic acidosis: an underrecognized risk factor for subsequent
      intubation requirement.
AB  - BACKGROUND: There are no published reports identifying an inadequate ventilatory
      response to metabolic acidosis as a predictor of impending respiratory failure.
      Metabolic acidosis should induce a respiratory alkalosis in which the partial
      pressure of carbon dioxide (Paco2) is (1.5 [HCO3-] + 8) +/- 2. This study
      examined the relation between inadequate ventilatory compensation and intubation
      among trauma patients. METHODS: A retrospective chart review was performed for
      trauma patients admitted between January 1999 and December 2000. Age, gender,
      Injury Severity Score and combined Trauma and Injury Severity Score, chest
      injury, history of cardiac or pulmonary disease, partial pressure of oxygen
      (Pao2), Paco2, Glasgow Coma Score, respiratory rate, systolic blood pressure,
      base deficit, and ability to compensate were analyzed with respect to intubation
      and need for ventilator support. RESULTS: Of 140 patients with metabolic
      acidosis, 45 ultimately were intubated. The mean Paco2 for the unintubated
      patients was 34 +/- 7 mm Hg, as compared with 41 +/- 11 mm Hg for the intubated
      patients (p < 0.001). Only injury severity and ability to compensate for
      metabolic acidosis were independent predictors of intubation. Patients with
      inadequate compensation were 4.2 times more likely to require intubation when
      control was used for the Injury Severity Score (95% confidence interval, 1.8-9.7;
      p < 0.001). CONCLUSIONS: Inability to mount an adequate hyperventilatory response
      to metabolic acidosis is associated with an increased likelihood of respiratory
      failure and a need for ventilatory support. Recognition of this relation should
      lead to closer monitoring of patients with this condition, and could help to
      avert unforeseen crisis intubations. This observation needs to be validated in a
      prospective study.

PMID- 15580023
TI  - Variability in trauma center outcomes for patients with moderate intracranial
      injury.
AB  - BACKGROUND: The variability of outcome between Trauma Centers has not been
      extensively studied as a possible avenue for performance improvement. Trauma
      Center variability in severity-adjusted survival for patients with moderate
      intracranial injury (MII) was studied in order to determine the association of
      MII-related process of care variables with outcomes. The analytic results were
      supplemented with peer review of MII patients with unexpected outcomes and
      identified potential process of care variables. METHODS: A retrospective cohort
      study was undertaken based on data submitted to a statewide trauma center
      database from July '95 through June '98. MII patients had one or more selected
      ICD-9-CM codes with an AIS-90 severity score of 3 or 4 but no higher. Severity
      adjustment was done using case matching and a logistic function based New Model
      that appropriately accounts for patients intubated on Emergency Department
      arrival. MII-related process of care variables derived from the database were
      identified and their relationship with outcome were evaluated individually and
      using multivariate methods. Trauma center personnel conducted standardized peer
      reviews. RESULTS: The study included data from 6765 patients treated at 26 trauma
      centers. Two centers (2PZW) had significantly more survivors than expected by
      both severity adjustment methods. Three had significantly fewer survivors than
      expected (3NZW). By several measures, patients treated in the 2PZW centers were
      more seriously injured and older than those in the 3NZW centers. CT of the head
      performed in the treating hospital was the only process of care variable
      associated with outcome in multivariate evaluations. Peer review also found
      little association between process of care variables and patient outcomes.
      However, peer review reported that 23.7% of unexpected deaths identified by case
      matching or the New Model were preventable or potentially preventable. Peer
      review also identified as medically unnecessary significant percentages of
      patients with unexpectedly long stays in hospital (26.4%) or in ICU (17.3%)
      identified by case matching. Nearly 45% of unexpected complications were judged
      preventable or potentially preventable. CONCLUSIONS: Two severity adjustment
      methods identified significant variability in trauma center outcomes for patients
      with MII. The difference in outcomes between the centers with better than
      expected (2PZW) and poorer than expected outcomes (3NZW) was substantial. Peer
      review identified significant opportunities for reducing unexpected deaths, stays
      in hospital and in ICU, and the occurrence of complications. Trauma registry data
      and peer reviews found little relationship between available process of care
      variables and patient outcomes. This study should stimulate discussions to
      understand reasons for outcome variability and ways to reduce it.

PMID- 15580024
TI  - Glial fibrillary acidic protein in serum after traumatic brain injury and
      multiple trauma.
AB  - BACKGROUND: This study aimed to determine whether glial fibrillary acidic protein
      (GFAP) is released after traumatic brain injury (TBI), whether GFAP is related to
      brain injury severity and outcome after TBI, and whether GFAP is released after
      multiple trauma without TBI. METHODS: This prospective study enrolled 114
      patients who had TBI with or without multiple trauma (n = 101) or multiple trauma
      without TBI (n = 13), as verified by computerized tomography. Daily GFAP
      measurement began at admission (<12 hours after trauma) and continued for the
      duration of intensive care (1-22 days). Documentation included categorization of
      computerized tomography according to Marshall classification, based on daily
      highest intracranial pressure (ICP), lowest cerebral perfusion pressure (CPP),
      lowest mean arterial pressure (MAP), and 3-month Glasgow Outcome Score (GOS).
      RESULTS: The GFAP concentration was lower for diffuse injury 2 than for diffuse
      injury 4 (p < 0.0005) or nonevacuated mass lesions larger than than 25 mL (p <
      0.005), lower for a ICP less than 25 mm Hg than for a ICP of 25 mm Hg or more,
      lower for a CPP of 60 mm Hg or more than for a CPP of 60 mm Hg or less, lower for
      a MAP of 60 mm Hg or more than for a MAP less than 60 mm Hg (all p < 0.0005), and
      lower for a GOS of 1 or 2 than for a GOS of 3, 4 (p < 0.05), or 5 (p < 0.0005).
      After TBI, GFAP was higher in nonsurvivors (n = 39) than in survivors (n = 62) (p
      < 0.005). After multiple trauma without TBI, GFAP remained normal. CONCLUSIONS:
      The findings showed that GFAP is released after TBI, that GFAP is related to
      brain injury severity and outcome after TBI, and that GFAP is not released after
      multiple trauma without brain injury.

PMID- 15580025
TI  - Comparison of cardiac outputs of major burn patients undergoing extensive early
      escharectomy: esophageal Doppler monitor versus thermodilution pulmonary artery
      catheter.
AB  - BACKGROUND: After major burn injury, severe hemodynamic fluctuations occur in a
      relatively short time, requiring invasive hemodynamic monitoring. The noninvasive
      esophageal Doppler monitor offers an alternative to the pulmonary artery
      catheter. This study compares the cardiac output of the esophageal Doppler
      monitor with that of a pulmonary artery catheter during the large volume shifts
      seen in extensive early escharectomy. METHODS: This study recruited 20 critically
      ill, major burn patients scheduled for elective early escharectomy. A
      thermodilution pulmonary artery catheter and esophageal Doppler monitor probes
      were inserted to measure cardiac output simultaneously at regular intervals. The
      results were analyzed by simple linear regression and Bland and Altman plots.
      RESULTS: The analysis included 92 data pairs from 20 patients, most of whom were
      critically ill with major burns. Escharectomy caused large intraoperative fluid
      shifts. The cardiac output of the esophageal Doppler monitor correlated
      moderately well with the cardiac output of the pulmonary artery, although it
      showed a mean of 15% less than the output of the pulmonary artery catheter. The
      mean bias was 0.77 L/minute, and the limits of agreement were +/-2.74 L/min.
      CONCLUSIONS: For major burn patients undergoing early escharectomy, the
      esophageal Doppler monitor allows changes in hemodynamics to be followed, but
      does not accurately measure the absolute values of cardiac output.

PMID- 15580026
TI  - Indocyanine-green fluorescence video angiography used clinically to evaluate
      tissue perfusion in microsurgery.
AB  - BACKGROUND: Laser-induced fluorescence angiography with indocyanine-green (ICG
      FA) is a new diagnostic approach that allows quantitative evaluation of tissue
      perfusion in microsurgery as well as an analysis of the uptake, distribution, and
      clearance of dye-marked blood. METHODS: The ICG-FA technique was evaluated for
      its sensitivity and prognostic value in comparison with clinical parameters
      (turgor, temperature, reperfusion time, bleeding after puncture) during and after
      different surgical procedures. Altogether, 91 measurements were made in cases of
      microvascular repair (n = 43) and free-flap surgery (n = 48). RESULTS: Because of
      discrepancies between ICG-FA results and clinical findings, the planned
      postoperative management was changed 43 times (47.2%). In cases of microvascular
      repair that subsequently resulted in tissue necrosis, ICG fluorescence had a
      significantly higher prognostic value than any of the clinical parameters (p =
      0.03). During free-flap surgery, intraoperative ICG-FA had better sensitivity for
      flap loss than clinical parameters, but postoperative ICG-FA did not.
      CONCLUSIONS: Fluorescence angiography with ICG is a sensitive diagnostic tool for
      detecting compromised tissue perfusion in trauma surgery and microsurgery. Its
      use may improve perioperative management and thereby lead to better clinical
      results.

PMID- 15580027
TI  - Nitrosoglutathione promotes flap survival via suppression of reperfusion injury
      induced superoxide and inducible nitric oxide synthase induction.
AB  - BACKGROUND: Evidence suggests that failure of flap reconstruction is related to
      ischemia/reperfusion (I/R)-mediated endothelial damage. Using a rat inferior
      epigastric artery flap as an I/R injury model, we investigated whether
      administration of nitrosoglutathione (GSNO), an exogenous nitric oxide (NO)
      donor, can scavenge superoxide and promote flap survival. METHODS: Thirty minutes
      before flap reperfusion, normal saline, N-acetylcysteine (75 and 150 mg/kg), or
      GSNO (0.2 and 0.6 mg/kg) was randomly injected into 10 rats. Superoxide, nuclear
      factor-kappa B (NF-kappa B) activation, NO synthase (NOS) isoforms, and 3
      nitrotyrosine expression in the pedicle vessels as well as survival areas of the
      flaps were evaluated. RESULTS: I/R injury induced superoxide production, NF-kappa
      B activation, and inducible NOS (iNOS) expression in the pedicle vessels. GSNO
      significantly inhibited superoxide production and suppressed NF-kappa B
      activation, iNOS induction, and 3-nitrotyrosine expression, but up-regulated
      endothelial NOS expression in the flap vessels. Optimal doses of both GSNO (0.6
      mg/kg) and N-acetylcysteine (150 mg/kg) effectively promoted flap survival area
      (p < 0.001), although there was no significant difference between both groups.
      CONCLUSION: Exogenous NO donation by GSNO can scavenge superoxide and suppress
      iNOS induction, resulting in better flap survival after prolonged ischemia.

PMID- 15580028
TI  - Suppression of transforming growth factor beta/smad signaling in keloid-derived
      fibroblasts by quercetin: implications for the treatment of excessive scars.
AB  - BACKGROUND: Keloids are characterized by abnormal proliferation and
      overproduction of extracellular matrix. Quercetin, a dietary compound, has strong
      antioxidant and anticancer properties. Previous studies by the authors have shown
      that quercetin inhibits fibroblast proliferation, collagen production, and
      contraction of keloid and hypertrophic scar-derived fibroblasts. Quercetin also
      blocks the signal transduction of insulin-like growth factor-1 in keloid
      fibroblasts. This study assessed the effects of quercetin on the transforming
      growth factor (TGF)-beta/Smad-signaling pathway in keloid-derived fibroblasts,
      which may be an important biologic mechanism of this proliferative scarring.
      METHODS: Keloid fibroblasts were isolated from keloid tissue specimens. Cells
      were treated with quercetin at different concentrations, then harvested, and
      subjected to immunoblotting analysis. RESULTS: Quercetin significantly inhibited
      the expression of TGF-beta receptors 1 and 2 in keloid fibroblasts at three
      concentrations (low, medium, and high). Quercetin also strongly suppressed the
      basal expression of Smad2, Smad3, and Smad4 as well as the phosphorylation of
      Smad2 and Smad3 and the formation of the Smad2-Smad3-Smad4 complex. CONCLUSIONS:
      Taken together, these data suggest that quercetin effectively blocks the TGF
      beta/Smad-signaling pathway in keloid fibroblasts. These data indicate that
      quercetin-based therapies for keloids should be investigated further.

PMID- 15580029
TI  - The use of the 3-mm K-Wire to supplement reduction of humeral supracondylar
      fractures in children.
AB  - BACKGROUND: Most children with humeral supracondylar fractures can be treated
      with simple closed reduction and cross-fixation with Kirschner (K)-wires.
      However, in a small proportion of cases, an acceptable closed reduction cannot be
      obtained, and open reduction becomes necessary. An alternative to open reduction
      is the use of a temporary 3-mm K-wire to manipulate and reduce the distal
      fragment. This report introduces the method of manipulation, as well as
      indications, and draws comparisons with complete close reduction cases. METHODS:
      Of 118 patients, 76 (64.4%) were managed with the standard closed reduction
      method and additional K-wire fixation to secure a good alignment (group 1). In
      the remaining 42 cases (35.6%), acceptable reduction could not be achieved by
      closed methods alone, and another temporary 3-mm K-wire was used to manipulate
      the distal fragment. After reduction of the fracture with the additional wire,
      standard cross K-wires were inserted to stabilize the fracture (group 2). As long
      as there was contact at the fracture site in cases of humeral supracondylar
      fracture, the traditional closed method was used easily to achieve excellent
      restoration. However, for cases in which the fracture site was totally displaced,
      and contact at the fracture site via traction was unsuccessful, a 3-mm K-wire was
      used to perform supplemental restoration treatment. All the patients, after the
      operation, were temporally immobilized with a long-arm splint for about 3 weeks.
      The fixation K-wires were removed after the radiograph had shown callus formation
      over the fracture site. Then the operation indications, operation methods and
      time, complications, and differences in range of motion were analyzed for these
      two sets of patients. RESULTS: The average group 1 surgery time was 18 minutes
      (range, 9-32 minutes), whereas the average surgery time for group 2 was 33
      minutes (range, 15-45 minutes). Three cases in group 1 were complicated with
      ulnar nerve injury caused by the fixation wire. There were no ulnar nerve
      injuries in group 2. However, the ulnar nerve injury complication rates for the
      two groups (3 in 76 for group 1; 0 in 40 for group 2) did not reach statistical
      difference (p = 0.5502, Fisher's exact test). The union times for the two groups
      were almost the same (average, 3 weeks; range, 2-5 weeks). The 3-mm K-wire
      manipulation reduction cases and the closed reduction cases seemed to yield the
      same healing results in all aspects, except for the longer surgery time in group
      2 (p < 0.0001). Both groups achieved satisfactory results. CONCLUSIONS: The
      closed reduction method should be used for children with humeral supracondylar
      fractures, whenever possible. The 3-mm K-wire manipulation method reduces the
      probability that open reduction will be required in some severe cases. This is a
      simple method without complications. The prognosis is the same as for closed
      reduction cases.

PMID- 15580030
TI  - An evaluation of two scoring systems to predict instability in fractures of the
      distal radius.
AB  - BACKGROUND: Various scoring scales have been introduced in the management of
      patients with multiple injuries and lower extremity injuries. Two scoring systems
      have been introduced to predict instability in distal radius fractures. The
      purpose of this investigation was to evaluate the accuracy of these two models in
      predicting instability. METHODS: A prospective study of 105 consecutive patients
      sustaining unilateral closed distal radius fractures was performed. Two scoring
      systems--the MacKenney formula and the Adolphson formula--were used to calculate
      the probability of fracture instability on the basis of initial presentation and
      injury films. The predicted probability of instability calculated from both
      models was then compared with actual results of instability on the basis of
      specific radiographic criteria at follow-up. RESULTS: Final follow-up information
      was available on 80 patients. There were 44 unstable fractures and 36 stable
      fractures at final follow-up. Using the MacKenney formula, of the 38 fractures
      predicted to have a low probability of instability (Pinstability < 30%), 18
      (47.4%) were found to be unstable. Using the Adolphson formula, of the 28
      fractures predicted to have a low probability of instability (Pstability > 70%),
      14 (50%) were actually unstable. CONCLUSION: Both scoring systems were found to
      underestimate the degree of fracture instability and to have a negative
      predictive value between 47 and 50% in a prospective series of patients. In
      fractures predicted to have a low probability of instability in both models, we
      found a poor correlation between predicted instability and actual instability.
      Our results demonstrate the limitations of two scoring systems in predicting
      fracture stability and in making clinical decisions on the basis of their
      results.

PMID- 15580031
TI  - Minimally invasive percutaneous plating of distal femoral fractures using the
      dynamic condylar screw.
AB  - BACKGROUND: In distal femoral fractures, conventional open reduction and internal
      fixation causes complications because of excessive soft-tissue stripping. To
      prevent this, minimally invasive percutaneous plating was performed in distal
      femoral fractures. METHODS: Sixteen supracondylar or intercondylar femoral
      fractures were treated by minimally invasive percutaneous plating with the
      dynamic condylar screw without bone graft. Five (31%) were open fractures.
      RESULTS: All fractures healed except one. The average time for fracture healing
      was 17 weeks (range, 14-22 weeks). Complications included one nonunion related to
      early full weight bearing. No patient showed malunion or deep infection. Results
      were evaluated by modified Neer rating, and all patients had excellent or good
      results. Intra-articular fractures showed less favorable range of motion and
      clinical scores than extra-articular fractures. CONCLUSION: Minimally invasive
      percutaneous plating with the dynamic condylar screw can provide favorable
      results in the treatment of distal femoral fractures.

PMID- 15580032
TI  - Exchange reamed nailing for aseptic nonunion of the tibia.
AB  - BACKGROUND: Exchange reamed nailing of the tibia is a common procedure in the
      treatment of an aseptic tibial nonunion. However, reports in the literature
      supporting this technique are limited. METHODS: Forty patients with a tibial
      nonunion after initial unreamed intramedullary nailing were retrospectively
      assessed after an exchange reamed nailing. The main outcome measurements included
      radiographic and clinical union as well as time from exchange reamed nailing to
      union. RESULTS: Thirty-eight patients achieved union of their fracture (95%). The
      average time from exchange nailing to union was 29 +/- 21 weeks. Complications
      included one deep vein thrombosis (2.5%) and two hardware failures (5%).
      CONCLUSION: Exchange reamed nailing for nonunions of the tibia results in a high
      union rate and is associated with a low complication rate. This technique is
      recommended as a standard procedure for aseptic tibial nonunions after initial
      unreamed intramedullary nailing.

PMID- 15580033
TI  - Effect of hyperbaric oxygen therapy on patellar tendinopathy in a rabbit model.
AB  - BACKGROUND: Hyperbaric oxygen therapy is a method for augmenting oxygen
      availability to tissues. This study investigated the effect of hyperbaric oxygen
      therapy on the collagenase-induced tendinopathy in the rabbit patellar tendon.
      METHODS: In this study, 13 rabbits were treated by ultrasound-guided injection of
      0.025 mL collagenase into the patellar tendon at the right knee, with the left
      knee serving as a control condition. The rabbits were randomly divided into two
      groups. After tendinopathy had been confirmed by histologic examination 3 weeks
      after treatment, hyperbaric oxygen therapy was initiated for group 1. The
      hyperbaric oxygen therapy involved 30 daily sessions of 2.5 ATA for 120 minutes
      starting 6 weeks after treatment. The rabbits in group 2 were put in normobaric
      room air. Both groups were killed 10 weeks after treatment. Histologic
      examinations as well as mechanical and biochemical tests were performed after the
      animals were killed. RESULTS: The ultimate tensile load in the tendon that had
      hyperbaric oxygen therapy was 34.8% greater than that in the control tendon 10
      weeks after treatment (p < 0.05). Hydroxyproline concentrations increased 82.2%
      simultaneously in the tendons that had hyperbaric oxygen therapy, as compared
      with the concentrations in the control tendons (p < 0.05). However, no
      statistical difference was found between the two groups in terms of pyridinoline
      concentration at the 10th week (p > 0.05). The histologic examination
      demonstrated an increase in blastlike tenocytes in group 1, with more mature
      phenotype, more organized collagen matrix, absence of myxoid degeneration, and
      increased vascularity at the 10th week, as compared with the control knee.
      CONCLUSIONS: The results validate the effectiveness of hyperbaric oxygen therapy
      in the treatment of tendinopathy. Hyperbaric oxygen therapy may increase collagen
      synthesis and collagen cross-link formation during the early healing process.

PMID- 15580034
TI  - Hospital factors associated with splenectomy for splenic injury: a national
      perspective.
AB  - BACKGROUND: The management of patients with splenic injury has shifted from
      routine splenectomy to attempts at splenic salvage. Using the Healthcare Cost and
      Utilization Project's National Inpatient Sample (HCUP-NIS), we assessed the
      patterns of care for splenic trauma. We hypothesized that the processes of care
      in urban and rural hospitals would differ. METHODS: Generalized estimating
      equations were used to identify predictor variables associated with laparotomy
      and splenectomy from a national, population-based sample of inpatients (HCUP
      NIS). Fourteen thousand nine hundred one patients with an International
      Classification of Diseases, Ninth Revision, Clinical Modification discharge
      diagnosis code of 865 were selected from the 1998 to 2000 HCUP-NIS data.
      Exclusion criteria included age greater than 80 years. Analyses were compared
      using all patients and excluding patients who died during the first 2 hospital
      days. RESULTS: Eight thousand five hundred fifty-three patients were treated in
      urban teaching hospitals. Forty percent underwent a laparotomy and 28% underwent
      a splenectomy at that time. Another 4,461 patients were cared for in urban
      nonteaching hospitals. Of these, 46% had a laparotomy and 35% underwent a
      splenectomy. The remaining 1,887 patients were seen in rural hospitals. Forty-six
      percent had a laparotomy and 36% had a splenectomy. Patients in urban teaching
      hospitals had lower risk-adjusted odds of splenectomy in multivariate models
      controlling for confounders including overall injury severity. Overall splenic
      salvage increased from 1998 to 2000, primarily because of increased salvage rates
      among urban teaching hospitals. CONCLUSION: The management of patients with
      splenic injury differs among urban teaching, urban nonteaching, and rural
      hospitals. Surgeons at urban teaching hospitals appear more willing to attempt
      splenic salvage by means of nonoperative management.

PMID- 15580035
TI  - Blunt abdominal trauma patients: can organ injury be excluded without performing
      computed tomography?
AB  - PURPOSE: The purpose of this study was to determine whether admission non
      computed tomography (CT) criteria can exclude intra-abdominal injury in stable
      patients sustaining blunt abdominal trauma. METHODS: Seven hundred fourteen
      hemodynamically stable patients with suspicion of blunt abdominal trauma were
      included in the study. Admission data for clinical examination, sonography,
      routine laboratory studies, chest/pelvic radiographic findings, and Glasgow Coma
      Scale (GCS) score were recorded. Each patient underwent helical abdominal CT.
      Injuries were considered major if they required surgery or angiographic
      intervention. At the authors' institution, angiography is routinely performed if
      there is a splenic injury of American Association for the Surgery of Trauma grade
      II or higher or a liver injury of American Association for the Surgery of Trauma
      grade III or higher. Statistical analysis was performed to determine the value of
      isolated and combined clinical, radiologic, and laboratory parameters in
      depicting an intra-abdominal injury with regard to CT results and clinical follow
      up. RESULTS: The best combination of criteria to identify a major abdominal
      injury was obtained when sonography, chest radiography, and three laboratory
      parameters (serum glutamic oxaloacetic transaminase, white blood cell count, and
      hematocrit) were normal: 22% (129 of 589) of patients without major injuries
      fulfilled these criteria. The only combination of criteria that completely
      excluded intra-abdominal injury was obtained when clinical criteria combined with
      a Glasgow Coma Scale score > 13, bedside radiologic studies, and laboratory data
      were all normal, but only 12% (68 of 578) of patients without abdominal injury
      fulfilled these criteria. CONCLUSION: After blunt abdominal trauma, admission non
      CT criteria can at best identify 12% of patients without intra-abdominal injuries
      and 22% of patients without major injuries.

PMID- 15580036
TI  - Vacuum-assisted fascial closure for patients with abdominal trauma.
AB  - BACKGROUND: Massive fluid resuscitation often is required for patients with
      intraabdominal trauma. Subsequently, fascial closure is not always possible in
      this subset of patients. Under these circumstances, an initial step can be the
      use of a temporary abdominal closure method. The authors currently use a vacuum
      assisted closure to manage the open abdomen for some of their trauma patients.
      They present their experience over the past 3 years. METHODS: From January 2000
      to December 2002, 48 trauma patients were treated with temporary abdominal
      closure using a vacuum-assisted dressing. The ultimate management of the
      abdominal defect, the serum lactate levels measured in the emergency department,
      and the fluid balance at the last attempt to accomplish fascial closure were
      reviewed. RESULTS: Delayed fascial closure was achieved in 23 (71.9%) of 32
      patients who survived to discharge (26 of 48, 54.2%). Of the 32 patients who
      survived to discharge, 9 (28.1%) required an alternative closure, most often a
      split-thickness skin graft. Of the 16 patients who died before discharge, 8 died
      within 24 hours after admission. Whereas 5 of the 16 deaths occurred after
      delayed abdominal closure, 11 patients died without abdominal closure. Emergency
      department serum lactate levels above 8 mg/dL show a positive correlation with in
      hospital mortality (6 of 16 patients; 38%; p = 0.001) and mortality within 24
      hours of admission (6 of 8 patients; 75%; p = 0.003). Admission lactate levels
      were not associated with the type of closure achieved. However, primary closure
      was associated with a significant decrease in lactate levels during the first 12
      hours. Complications included five abdominal abscesses, two enterocutaneous
      fistulas, and one split-thickness skin graft failure. CONCLUSIONS: Patients
      requiring temporary abdominal closure have a significant in-hospital mortality
      rate of 33%. Delayed primary closure with vacuum assistance was achieved for
      71.9% of the surviving patients. Maintaining a negative or total positive fluid
      balance of less than 20 L before the last attempted fascial closure improves
      successful closure rates, as seen in 19 of 22 patients (86.4%). The vacuum
      assisted closure technique also enabled successful primary closure for two
      patients with extreme delay (>8 days). Elevated serum lactate levels are
      significantly correlated with early and in-hospital mortality. A significant
      decrease in lactate level during the first 12 hours is associated with
      achievement of primary closure.

PMID- 15580037
TI  - The effects of total-body irradiation on the survival and skin wound healing of
      rats with combined radiation-wound injury.
AB  - To investigate the effects of total body irradiation on the healing of skin
      wounds, rats were irradiated with a (60)Co gamma-ray source, in which single
      doses ranged from 1 to 8 Gy. After irradiation, two whole-thickness circular skin
      wounds, 22 mm in diameter and covering 2.5% of the total body surface area, were
      made immediately on the back of each animal. The average healing time for the
      simple wound was 18.3 +/- 2.1 days, whereas when the wound was combined with 1,
      2, 3, 4, 5, and 6 Gy of radiation, the average wound healing time was delayed by
      0.3, 0.8, 1.1, 3.5, 6.2, and 9.5 days, respectively. The average healing time was
      significantly decreased with irradiation doses exceeding 4 Gy, as compared with
      the healing time for the simple wound without irradiation (p < 0.05). The
      statistical results showed that the percentage of the unclosed wound with the
      increased doses in combined radiation injury was significantly proportional to
      the recovery time kinetics.

PMID- 15580038
TI  - Kleihauer-betke testing is important in all cases of maternal trauma.
AB  - BACKGROUND: In maternal trauma, the Kleihauer-Betke (KB) test has traditionally
      been used to detect transplacental hemorrhage (TPH), so that Rh-negative women
      could receive appropriate Rh immune prophylaxis. Reasoning that the magnitude of
      TPH would reflect uterine injury, we evaluated Kleihauer-Betke testing as an
      independent predictor of preterm labor (PTL) after maternal trauma. METHODS:
      Admissions to the Shock Trauma Center, University of Maryland, from January 1996
      to January 2002, were reviewed. Of 30,362 trauma patients admitted, 166 were
      pregnant, and 93 of these underwent electronic fetal monitoring. Their records
      were abstracted for demographics, injury type, three separate trauma scores,
      documented uterine contractions, PTL (contractions with progressive cervical
      change), and serious perinatal complications. In 71 cases, transplacental
      hemorrhage was assessed by maternal KB test. RESULTS: TPH, defined as KB-positive
      for greater than 0.01 mL of fetal blood in the maternal circulation, occurred in
      46 women. Forty-four had documented contractions (25 had overt PTL) and 2 had no
      contractions. In 25 women with a negative KB test, none had uterine contractions.
      All patients with contractions or PTL had positive KB tests. By logistic
      regression, KB test result was the single risk factor associated with PTL (p <
      0.001; likelihood ratio, 20.8 for positive KB test). Compared with other sites,
      abdominal trauma was associated more often with uterine contractions (p < 0.001),
      PTL (p = 0.001), and a positive KB test (p < 0.001, chi). None of the trauma
      scoring systems predicted PTL. CONCLUSION: Kleihauer-Betke testing accurately
      predicts the risk of preterm labor after maternal trauma. Clinical assessment
      does not. With a negative KB test, posttrauma electronic fetal monitoring
      duration may be limited safely. With a positive KB test, the significant risk of
      PTL mandates detailed monitoring. KB testing has important advantages to all
      maternal trauma victims, regardless of Rh status.

PMID- 15580039
TI  - Liver trauma: management of devascularization injuries.

PMID- 15580040
TI  - Anaphylactoid reaction to oral contrast for computed tomography.

PMID- 15580041
TI  - Multilevel blunt duodenal injury.

PMID- 15580043
TI  - Traumatic subperiosteal pseudoaneurysm: a case report.

PMID- 15580042
TI  - Delayed development of infrarenal abdominal aortic pseudoaneurysm after blunt
      trauma: a case report and review of the literature.

PMID- 15580044
TI  - Delayed neurotuberculosis after closed traumatic brain injury.

PMID- 15580045
TI  - Chylous knee effusion: is it septic arthritis? A case report and review of
      literature.

PMID- 15580046
TI  - An unusual case of elbow dislocation in a child: crossover of radius and ulna.

PMID- 15580047
TI  - The impact of the 2003 blackout on a level 1 trauma center: lessons learned and
      implications for injury prevention.

PMID- 15580048
TI  - Glucose control by insulin for critically ill surgical patients.

PMID- 15580049
TI  - Cervical impalement injury in a nonagenarian.

PMID- 15580050
TI  - Retained cervical stabbing implement with associated ischemic spinal cord injury.

PMID- 15580051
TI  - Comment on "Penetrating head injury caused by bear claws: case report".

PMID- 15580053
TI  - Promoting heart health: building on the European Council conclusions from Cork.

PMID- 15580055
TI  - The cost-effectiveness of the use of clopidogrel in acute coronary syndromes in
      five countries based upon the CURE study.
AB  - BACKGROUND: The CURE study demonstrated that clopidogrel prevents a range of
      ischaemic cardiovascular events in patients with Acute Coronary Syndromes
      (unstable angina or non-ST-segment elevation MI). DESIGN: We undertook an
      economic analysis of the use of clopidogrel in the UK, USA, Sweden, France and
      Canada based on the CURE study. METHODS: The costs of hospitalization, study drug
      and other medications were calculated, based on resource utilization for all
      patients in CURE. Unit costs were obtained for all resource items for each
      country, and are reported in local currencies in 2001 prices. RESULTS: While
      hospitalization costs were lower in the clopidogrel group, when the acquisition
      cost of clopidogrel for 9 months is included, the average cost per patient is
      higher in the clopidogrel group than the placebo group in all countries
      [difference in costs (with 95% CI) 208 pounds sterling (119, 297), 451 US dollars
      (58, 845), SKr 2571 (728, 4412), 325 euros (85, 565), 161 Canadian dollars (-185,
      506)]. The absolute reduction in the number of total primary events was 2.0%,
      resulting in an incremental cost-effectiveness ratio (ICER) of 10,366 pounds
      sterling in the UK, 22,484 US dollars in the USA, SKr 127,951 in Sweden, 16,186
      euros in France, and 7973 Canadian dollars in Canada per primary event avoided
      with clopidogrel. CONCLUSIONS: Clopidogrel in CURE reduced hospitalization costs
      but the acquisition cost of clopidogrel creates an overall increase in direct
      health care costs over 9 months. Nevertheless, the cost-effectiveness is in a
      range comparable to other therapies currently utilized for acute coronary
      syndromes.

PMID- 15580057
TI  - Helicobacter pylori and hepatitis A virus infections and the cardiovascular risk
      profile in patients with diabetes mellitus: results of a population-based study.
AB  - OBJECTIVE: The objective of this study was to investigate the associations of
      sero-positivity for Helicobacter pylori (HP) and hepatitis A virus infection
      (HAV) with prevalence of cardiovascular diseases (CVD) and CVD-risk markers in a
      large population-based sample of patients with diabetes mellitus (DM), who are at
      high risk of developing CVD. BACKGROUND: Several studies have suggested that
      chronic infections are associated with the development of atherosclerosis and
      coronary heart diseases (CHD). METHODS: This analysis is based on the German
      National Health Interview and Examination Survey which was conducted in 1998. We
      identified all subjects with prevalent DM aged 40-79 years. Helicobacter pylori
      and HAV status were measured by serum immunoglobulin G antibodies. Prevalence of
      several CVD events (myocardial infarction, stroke and CHD) was recorded. In
      addition, serum levels of total triglycerides, total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a)
      were measured. RESULTS: Among the 4285 participants of the German Health Survey
      aged 40-79 years, we identified 365 patients with DM. Of these, 32.1% had at
      least one CVD and there was a clear increase of CVD with age. Sero-prevalence of
      HP or HAV and their combination was not associated with the prevalence of CVD nor
      with mean levels of blood lipids after multivariate adjustment for covariates.
      CONCLUSION: In this large group of 365 patients with diabetes mellitus no
      association of HP and HAV sero-prevalence with presence of CVDs or the level of
      serum lipids was established. Therefore it seems unlikely that HP and HAV sero
      prevalence strongly influence CVD progression in patients with diabetes.

PMID- 15580056
TI  - Declining incidence and mortality of stroke in persons aged > or = 75 years in
      Finland; the FINSTROKE study.
AB  - BACKGROUND: The average life expectancy of a person aged 75 in Finland is
      approximately 10 years. A substantial threat to the quality of life during these
      years is stroke, which is common among the elderly, may hamper independent living
      and places a substantial burden on health care resources. The aim of the present
      study was to analyse the trends in incidence, mortality and prognosis of acute
      stroke events in persons aged > or = 75 years in Finland. DESIGN: A population
      based stroke register study. METHODS: The FINSTROKE register recorded all stroke
      events in persons aged > or = 75 years (n=5493) among inhabitants of the town of
      Turku from 1982 to 1992 and again from 1996 to 1998, and in the Kuopio area from
      1990 to 1997. RESULTS: At the end of the study period, the age group > or = 75
      years constituted 3.8% of the population of study areas among men and 8.7% among
      women. This population segment contributed 35% of strokes among men and 66% among
      women. Of all strokes in this age group, 73% occurred among women. Data suggested
      that the mortality and incidence of acute stroke events were declining, but the
      28-day case fatality did not change. At day 28 after the onset of stroke, only
      26% of men and 19% of women had recovered well enough to be capable of
      independent living. CONCLUSIONS: Stroke mortality among the elderly is declining
      in Finland, which is mainly due to the decline in the incidence of stroke events.

PMID- 15580058
TI  - The paradoxical association of common polymorphisms of the renin-angiotensin
      system genes with risk of myocardial infarction.
AB  - BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting
      enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor
      (AT1R) have been extensively investigated as possible risk factors for myocardial
      infarction (MI). DESIGN AND METHODS: Genetic association, case-control study,
      specifically designed to investigate the association of the above-mentioned
      polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian
      population. The study population consisted of 1603 consecutive patients with
      acute MI who were recruited from nine clinics, located in three cities, and 699
      unrelated adults who were randomly selected from the city catalogues. RESULTS: In
      univariate analysis, the DD genotype was found to be more prevalent among
      controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age,
      gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension
      and family history of coronary artery disease, the presence of the DD genotype
      was independently and negatively associated with risk of AMI (RR=0.743, 95%
      CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly
      associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in
      multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473
      1.167, P=0.197). CONCLUSIONS: Contrary to previous reports, in this study the DD
      genotype of the ACE gene, but not the CC genotype of the AT1R gene, was
      associated with a lower risk of MI. Our results emphasize the complexity of
      genotype-phenotype interactions in the pathogenesis of ischaemic heart disease
      and question the previously hypothesized role of the DD genotype on risk of acute
      myocardial infarction.

PMID- 15580059
TI  - Lipid levels and the use of lipid-lowering agents in England and Scotland.
AB  - OBJECTIVE: Preventing cardiovascular events with lipid-lowering drugs has been
      established in several trials reported since 1994. Consequently national
      guidelines recommend statins for those with established cardiovascular disease
      (CVD) and those at high risk of developing CVD. We evaluated blood lipid levels,
      and compare treatment and control of dyslipidaemia in English and Scottish adults
      with national recommendations for lipid lowering. DESIGN AND METHODS: In 1998 the
      nationally-representative Health Survey for England and the Scottish Health
      Survey included valid cholesterol results for 9631 (England) and 6065 (Scotland)
      adults aged 16-74. Mean blood levels of total, high-density lipoproteins (HDL-),
      and total:HDL-cholesterol ratio; prevalence of elevated total cholesterol levels,
      and total:HDL-cholesterol ratios; prevalence of use of lipid-lowering agents in
      high risk subgroups; and lipid levels of those on treatment were calculated.
      RESULTS: Levels of dyslipidaemia, treatment and control were not significantly
      different between Scotland and England. Combining these data, mean total
      cholesterol levels were 5.43 and 5.48 mmol/l in men and women respectively; and
      mean HDL-cholesterol levels were 1.29 and 1.56 mmol/l. Overall 64.6% of adults
      had a total cholesterol > or =5 mmol/l, 24.6% had a total:HDL ratio > or =5 and
      2.3% reported taking lipid-lowering drugs. Treatment rates among those with a
      total cholesterol >5 mmol/l and a history of coronary heart disease or stroke,
      hypertension, or diabetes, were 27.3%, 15.4% and 17.8% respectively, and control
      rates (total cholesterol <5 mmol/l) among those treated were 45.3%, 38.5% and
      32.7%. CONCLUSIONS: Low treatment rates with lipid-lowering drugs existed
      overall, among high-risk patients suitable for primary prevention, and among
      those with established cardiovascular disease.

PMID- 15580060
TI  - Inspiratory muscle training using an incremental endurance test alleviates
      dyspnea and improves functional status in patients with chronic heart failure.
AB  - BACKGROUND: The benefits of inspiratory muscle training (IMT) in patients with
      chronic heart failure (CHF) have been inadequately studied. DESIGN AND METHODS:
      Using a prospective, age and sex-matched controlled study, we investigated 35
      patients with moderate to severe CHF (NYHA class II-III and left ventricular
      ejection fraction 24.4+/-1.3% [mean+/-SEM]). An incremental respiratory endurance
      test using a fixed respiratory workload was provided by software with an
      electronic mouth pressure manometer interfaced with a computer. The training
      group (n=20) exercised at 60% of individual sustained maximal inspiratory
      pressure (SMIP) and the control group (n=15) at 15% of SMIP. All patients
      exercised three times weekly for 10 weeks. Pulmonary function, exercise capacity,
      dyspnea and quality of life were assessed, pre- and post-training. RESULTS: The
      training group significantly increased both maximum inspiratory pressure (Pimax),
      (111+/-6.8 versus 83+/-5.7 cmH2O, P<0.001), and SMIP (527822+/-51358 versus
      367360+/-41111 cmH2O/sec x 10(-1), P<0.001). Peak VO2 increased after training
      (17.8+/-1.2 versus 15.4+/-0.9 ml/kg/min, P<0.005), as did the six-minute walking
      distance (433+/-16 versus 367+/-22 meters, P<0.001). Perceived dyspnea assessed
      using the Borg scale was reduced for both the treadmill (12.7+/-0.57 versus
      14.2+/-0.48, P<0.005) and the walking (9+/-0.48 versus 10.5+/-0.67, P<0.005)
      exercise tests and the quality of life score was also improved (21.1+/-3.5 versus
      25.2+/-4, P<0.01). Resting heart rate was significantly reduced with training
      (77+/-3.3 versus 80+/-3 beats/min, P<0.05). The control group significantly
      increased Pimax (86.6+/-6.3 versus 78.4+/-6.9 cmH2O, P<0.05), but decreased SMIP
      (274972+/-32399 versus 204661+/-37184 cmH2O/sec x 10(1), P<0.005). No other
      significant effect on exercise capacity, heart rate, dyspnea, or quality of life
      was observed in this group. CONCLUSION: Inspiratory muscle training using an
      incremental endurance test, successfully increases both inspiratory strength and
      endurance, alleviates dyspnea and improves functional status in CHF.

PMID- 15580061
TI  - Attenuation of inflammation with short-term dietary intervention is associated
      with a reduction of arterial stiffness in subjects with hypercholesterolaemia.
AB  - BACKGROUND: Increased arterial stiffness has been found in patients with chronic
      high-grade inflammatory diseases. Whether mitigation of low-grade systemic
      inflammation, through a low-cholesterol/low-saturated fat diet, may have a role
      in improving arterial stiffness is still untested. DESIGN: We investigated
      whether variations in blood lipids and plasma C-reactive protein induced by low
      cholesterol/low-saturated fat diet are associated with variations in large-artery
      stiffness in hypercholesterolaemia. METHODS: Thirty-five patients with primary
      hypercholesterolaemia and 15 normal control subjects were recruited for the
      study. Hypercholesterolaemic patients followed an 8-week low-cholesterol/low
      saturated fat diet (30% total fat, 5% saturated fat, cholesterol <200 mg/daily).
      Anthropometric characteristics, blood lipids, plasma C-reactive protein and
      arterial stiffness were measured at baseline and after the diet. RESULTS:
      Arterial stiffness and C-reactive protein levels were higher in
      hypercholesterolaemic patients than in controls. Significant reductions in body
      weight (2 kg, 3%), plasma total cholesterol (13.4 mg/dl, 5.3%), low-density
      lipoprotein cholesterol (11.2 mg/dl, 6.4%), C-reactive protein (0.7 mg/l, 39%)
      and arterial stiffness (from 8.9+/-2.0 to 8.1+/-1.9 m/s, 11%) were achieved among
      hypercholesterolaemic patients after the 8-week diet (P<0.05 for all). Bivariate
      correlations and multivariate analysis showed reduction in arterial stiffness
      after short-term diet to be associated with reduction of plasma C-reactive
      protein levels (r=0.59, beta=0.38, P<0.05 for both). CONCLUSIONS: Short-term low
      cholesterol/low-saturated fat diet in hypercholesterolaemia may be effective in
      improving large artery stiffness, likely through the mitigation of low-grade
      systemic inflammation.

PMID- 15580062
TI  - Effect of nutritional composition of meals on exercise tests in patients with
      ischaemic heart disease.
AB  - BACKGROUND: Patients with ischaemic heart disease have to perform exercise tests
      repeatedly. It is not clear if a small meal eaten before the test might influence
      it and if the meal's composition is important. DESIGN AND METHOD: We performed a
      double blind, randomised, crossover study on 20 volunteers with documented
      ischaemic heart disease known to have positive exercise tests. Each had three
      symptom limited exercise tests done one hour after a 200 ml meal, rich in either
      fat, carbohydrate or protein. Each postprandial test was compared to a fasting
      exercise test performed just before the meal. RESULTS: Postprandial blood
      pressure, time to angina and to peak exercise and double product at onset of ST
      depression were not significantly altered by any of the meals. Heart rate was
      slightly increased only after the fat meal. CONCLUSIONS: The nutritional
      composition of a small meal eaten an hour before an exercise test has no
      clinically important impact on the results of the test in patients with stable
      angina pectoris.

PMID- 15580063
TI  - Paraoxonase-1 gene Leu-Met55 and Gln-Arg192 polymorphisms are not associated with
      carotid artery atherosclerosis in a population-based cohort.
AB  - BACKGROUND: Paraoxonase-1 (PON1) is an enzyme that prevents low-density
      lipoprotein (LDL) oxidation. The role of polymorphisms of PON1 determining early
      atherosclerotic changes is currently unclear. DESIGN: Cross sectional cohort
      study. METHODS: Nine hundred and ninety-nine subjects from a population-based
      cohort were screened. Intima-media thickness (IMT) was measured by
      ultrasonography. Leu-Met55 and Gln-Arg192 polymorphism were determined. RESULTS:
      No association between PON1 genotypes and IMT was found. This finding remained
      after adjusting for confounding factors. CONCLUSIONS: The PON1 Leu-Met55 and Gln
      Arg192 polymorphisms are not major risk factors for atherosclerosis in the
      general Caucasian population.

PMID- 15580064
TI  - Nutritional counselling in primary health care: a randomized comparison of an
      intervention by general practitioner or dietician.
AB  - AIMS: To compare health effects and risk reduction in two different strategies of
      nutritional counselling in primary health care for patients at high risk of
      ischaemic heart disease. METHODS: In a cluster-randomized trial 60 general
      practitioners (GPs) in the Copenhagen County were randomized to give nutritional
      counselling or to refer patients to a dietician. Patients were included after
      opportunistically screening (n=503 patients), and received nutritional
      counselling by GP or dietician over 12 months. Health effects were measured by
      changes in weight, waist circumference and blood lipids. Risk of cardiovascular
      disease was calculated by The Copenhagen Risk Score. Data on use of medicine and
      primary health care was obtained from central registers. RESULTS: Altogether 339
      (67%) patients completed the intervention. Weight loss was larger in the
      dietician group (mean 4.5 kg vs. 2.4 kg), and increase of HDL-cholesterol was
      larger in the GP group (mean 0.13 mmol/l vs. 0.03 mmol/l). The reduction of the
      cardiovascular risk score was significantly larger in the GP group (P=0.0005).
      Other health outcomes were not significantly different. CONCLUSIONS: GPs were
      aware of substantial risk factors of cardiovascular disease and addressed these
      when counselling. The guidance from a GP was of significant importance for risk
      reduction in relation to IHD. However, a long-term lifestyle intervention by GP
      was difficult to implement. In the case of obesity it was effective to refer to
      long-term nutritional counselling by a dietician.

PMID- 15580065
TI  - Cardiovascular risk and diabetes. Are the methods of risk prediction
      satisfactory?
AB  - BACKGROUND: Methods available to predict cardiovascular disease (CVD) and
      coronary heart disease (CHD) risk include the Joint British Societies Risk Chart
      (JBSRC), the CardioRisk Manager (CRM) calculator, the PROCAM calculation and
      specific to diabetes, the UKPDS risk engine. Our aim was to examine their
      efficacy in a clinic-based population of diabetic patients. DESIGN: Patients were
      identified who attended clinic at baseline (1990-1991) and categorised by the
      presence/absence of CHD/CVD at follow-up (2000-2001). Ten-year risk was
      calculated using JBSRC, CRM, PROCAM and the UKPDS risk engine. METHODS: A total
      of 798 patients were identified under follow-up (2000-2001), with sufficient data
      for risk prediction. Risk prediction methods were assessed by: (1) the Hosmer
      Lemeshow test (calibration test); (2) the C-index, derived from the ROC curve [a
      discriminatory measure ranging from 0.5 (no discrimination) to 1.0 (perfect
      discrimination)]; and (3) Spearman correlation of the observed and predicted
      risk. RESULTS: All tests (except PROCAM) demonstrated acceptable discrimination
      with respect to CHD/CVD, however, all underestimated the risk of future events.
      With respect to CVD, the JBSRC had a C-index of 0.80, CRM: 0.76, UKPDS: 0.74 and
      PROCAM: 0.67. With respect to CHD the C-indexes were 0.77, 0.73, 0.65 and 0.76
      respectively. Risk prediction by CRM had a stronger relationship with observed
      events than UKPDS and PROCAM (r=0.97, 0.86, 0.81 respectively). CONCLUSIONS: All
      scores have reasonable discrimination, but underestimate future events. The CRM
      showed the strongest correlation between observed and predicted risk with the
      least amount of scatter from the line of best fit. The CRM, when adjusted by the
      calibration factor, provides the most accurate method of risk prediction.

PMID- 15580067
TI  - NHS is failing older people with chronic conditions.

PMID- 15580068
TI  - The proposed assisted dying bill negates end-of-life care.

PMID- 15580069
TI  - Nurses must be more vocal about public health.

PMID- 15580070
TI  - Preventing hip fracture in care homes 1: views of residents and staff.
AB  - Hip protectors have been shown to be effective in reducing the incidence of hip
      fracture among older people living in care homes (Parker et al, 2004). However,
      there are problems with compliance. This article reports findings from a survey
      of 138 staff from 23 care homes about experiences and perceptions of using hip
      protectors. The survey was complemented by qualitative case studies involving
      staff, to be linked to compliance with wearing hip protectors including comfort,
      acceptability to the resident and appearance. Few practical difficulties in using
      hip protectors were identified. Staff and residents' perceptions and experiences
      of using hip protectors vary and are likely to influence compliance.

PMID- 15580071
TI  - Supporting care homes: the older people's specialist nurse.
AB  - This article outlines the health needs of older nursing home residents and
      identifies the case for the role of an older people's specialist nurse within a
      multidisciplinary care homes support team (CHST). This model has been
      successfully introduced in the London boroughs of Lambeth, Southwark and Lewisham
      as a response to the profile of local health need among care home residents and
      changes in national policy such as the introduction of NHS-funding nursing care.
      The structure of the CHST is described, and the older people's specialist nurse
      is discussed in detail. The emergent role of the older people's specialist nurse
      as key to managing the interface between the nursing homes and primary care is
      highlighted as a key benefit of this unique role.

PMID- 15580072
TI  - Challenges for care homes: education and training of healthcare assistants.
AB  - The spotlight is increasingly on all care homes, including those catering
      specifically for older people, to deliver on quality targets in an attempt to
      drive up the standards of care provision. These targets include the education,
      training and supervision of care staff. Representing a major component of the
      care staff workforce in care homes are healthcare assistants and they play a key
      role in care provision and will continue so to do. However, pivotal to their
      effective role performance is preparation and support - the provision of which
      has been patchy to date. For care homes that provide nursing care the challenges
      of delivering on these targets by 2005 are significant, particularly as the
      majority of these homes are run as private enterprises and in the absence of any
      form of central funding. This article examines key issues to education and
      training provision. A strategic nationwide approach to education and training for
      healthcare assistants in care homes is recommended, coupled with robust
      evaluation of outcomes. Such initiatives will need to be supported by significant
      financial investment if the Government's targets are to be achieved.

PMID- 15580073
TI  - Multiprofessional follow up of patients after subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) is a life-threatening illness that affects people
      suddenly and without warning. Previous research has estimated that only 7% of SAH
      survivors suffer physical deficits (Stegan and Freckmann, 1991), whereas two
      thirds of those classed as having made a good recovery actually experience a
      range of debilitating cognitive or emotional difficulties (Bindschaedler et al,
      1997); Buchanan et al, 2000). At Hope Hospitals, a structures system was set up
      to help support the survivors of SAH through follow-up via the neurovascular team
      providing patients with information, guidance and early intervention including
      screening for potential cognitive and emotional difficulties and fast-track
      referral to neuropsychology services. Behavioural indices demonstrated that
      patients experienced a range of difficulties in everyday functioning such as
      problems that prevent a return to work and excessive fatigue, among others.
      Although this innovative system does address follow-up need, improvements could
      be made to ensure that all patients receive an equitable service.

PMID- 15580074
TI  - Professional holistic care of the person with a stoma: online learning.
AB  - Stoma care nurse specialists are valued for their diverse expertise, but it is
      essential that all practitioners who regularly care for people with stomas have
      the opportunity to develop professionally and influence this important area of
      practice. The vision of a clinical and educational team from Suffolk and south
      Norfolk led to the development of innovative web-based learning material. The aim
      is to inspire nurses to engage actively with people who have a stoma.
      'Professional care of the person with a stoma' is about caring for the whole
      person, physically and emotionally, from the period before surgery, to their
      continuing care in the community. An overview of four aspects of stoma care is
      presented here as a way of sharing with a wider audience the expert practice
      harnessed during the development of this web-based module.

PMID- 15580075
TI  - Managing a breast sinus wound in the community: a care study.
AB  - The district nursing team had to manage a breast sinus wound which produced
      copious amounts of exudate and caused further problems because of its shape and
      position. Using a hydrofibre dressing the wound successfully healed without
      causing any problems with maceration to the surrounding skin. However, the nurses
      were unsure as to what was the correct amount of dressing to pack into the wound,
      and there are no specific guidelines on how tightly to pack wounds and this can
      influence the successful outcome of wound healing. In addition, this case showed
      the impact of the patient's altered body image as a result of her mastectomy.

PMID- 15580076
TI  - An investigation to find strategies to improve student nurses' maths skills.
AB  - Being able to perform drug calculations accurately is an essential skill for
      nurses. Many studies, however, have demonstrated that nurses need to improve this
      area of their practice and in particular their mathematical skills. Several
      strategies have been implemented to develop the drug calculation skills of
      nurses, with mixed success. This article reports on a study that was carried out
      to investigate whether strategies implemented within a second-year pre
      registration course were perceived by students to be helpful in improving their
      mathematical skills for drug calculations. The results demonstrated that students
      felt their mathematics and confidence improved as a result of these strategies.
      The students' evaluation of the learning strategy that they found most helpful in
      learning drug calculation gave a mixed result, indicating that students have
      differing learning styles and needs. The study also indicates that student nurses
      were able to integrate the mathematical skills into their nursing practice by
      having different strategies that allowed them to develop conceptual, mathematical
      and practical skills concurrently. The study recommends the implementation of
      integrated strategies to address drug calculation skills in student nurses,
      although further research is still required.

PMID- 15580077
TI  - Review of recommendations for reforms to the coroner's office.
AB  - The Inquiry that was set up following the conviction of Dr Shipman for the murder
      of 15 of his patients produced three reports, the third of which considered the
      present system for death and cremation certification and the investigation of
      deaths by coroners (Shipman Inquiry, 2003b). The report makes extensive
      recommendations for reform of the coroner's office regarding the certification of
      death. This article outlines the recommendations made by the third report of the
      Shipman Inquiry and reviews the potential implications of such legislation.

PMID- 15580078
TI  - Staff nurse who had an alcohol problem and made nursing errors.

PMID- 15580079
TI  - Exploring the relationship between caring, love and intimacy in nursing.
AB  - This article uses the five distinct perspectives on caring proposed by Morse et
      al (1990) to illustrate the relationship between love, intimacy and caring. Two
      distinct types of love, namely Agape (altruism/charity) and filia (brother love)
      are utilized in nursing. Only some caring relationships with patients reach an
      intimate level, and this is determined by patient characteristics to which the
      nurse responds. It is concluded that caring as a moral imperative is the most
      relevant to discussions on caring in nursing and the perspective on which the
      other four viewpoints hinge.

PMID- 15580080
TI  - Managing faecal incontinence or leakage: the Peristeen Anal Plug.
AB  - Incontinence can be a devastating problem to many individuals. It is embarrassing
      and limiting socially, and prevents those with the problem from going about their
      day-to-day activities. People adopt coping strategies to manage the problem and
      those with urinary incontinence often look for containment products such as
      disposable pads or nappy-style products. These products have been developed using
      different absorbent materials and are accessible to sufferers in local
      supermarkets. Absorbency of the products has improved so that once wetted, they
      hold urine more easily. However, the same cannot be said for faecal incontinence
      management products and there are few that can be called upon to manage this
      devastating condition. The Peristeen Anal Plug, developed originally as the
      Conveen Anal Plug, stands alone in the search for a device to manage faecal
      incontinence or leakage.

PMID- 15580081
TI  - RCN warns that the nursing profession is in danger.

PMID- 15580082
TI  - The theory-practice gap still exists in nursing education.

PMID- 15580083
TI  - Thrombolysis for acute ischaemic stroke and the role of the nurse.
AB  - This article describes thrombolysis for acute ischaemic stroke as an emerging
      treatment modality. National clinical guidelines emphasized the need to identify
      acute stroke as a clinical priority and to develop protocols for the early
      assessment and treatment of stroke patients. Fast-track services developed in
      other clinical scenarios have proven successful and this article outlines the
      potential benefits of a fast-track service for acute stroke. The role of the
      clinical nurse specialist in stroke is central to this service; this role
      includes development and implementation of fast-track protocols in accident and
      emergency, rapid assessment for eligibility of thrombolysis and coordinating post
      thrombolysis monitoring and acute stroke care.

PMID- 15580084
TI  - The use of practice guidelines for urinary incontinence following stroke.
AB  - Incontinence is common following stroke, but there is little stroke-specific
      evidence to guide treatment and interventions for this condition. National
      clinical guidelines for stroke specify that all wards should have management
      protocols for urinary incontinence and yet, according to the recent Sentinel
      Stroke Audit result, many wards do not have this information available. This
      article describes the implementation of guidelines on a stroke unit within an NHS
      associate teaching hospital and describes the impact on patient care using
      clinical audit. The results indicate that patient care and outcome is improved
      following implementation. Recommendations are being made for information sharing
      and further research.

PMID- 15580085
TI  - Nursing management of urinary tract infections for catheterized patients.
AB  - Nosocomial urinary tract infections account for up to 40% of all hospital
      acquired infections with 80% of these associated with the use of urinary
      catheters. The most important risk factor for infection is duration of
      catheterization. Clinical practices in catheter management vary widely and
      frequently are not evidence-based. It is vital that all indwelling catheters
      should be connected to a sterile closed urinary drainage system and that the
      connection between the catheter and the urinary drainage system is not broken
      except for good clinical reasons. Catheter care is a nursing procedure the
      importance of which is sometimes overlooked and cleansing of the perineum and
      meatus should be performed twice daily using soap and water.

PMID- 15580086
TI  - Setting standards for assessment of ward patients at risk of deterioration.
AB  - Improving the care of critically ill patients is a key objective of the
      Department of Health (DoH, 2000). Research findings and anecdotal evidence
      suggest that the key indicators of developing critical illness (respiratory rate
      and fluid balance) are being missed on busy general medical and surgical wards.
      In order to address this issue, the East Somerset NHS Trust critical care
      outreach team, in collaboration with ward staff, created the Amber Project. This
      project aimed to identify clearly patients who were at risk of deterioration and
      provide qualified nurses with a clear framework and minimum standard for
      assessment and observation. The project ran from June to September 2003. Results
      indicated that on the ward using the amber system the frequency of patient
      observations increased compared to those found on two other general wards.
      Nursing staff reported feeling more confident with regard to assessment and
      prioritizing care. Junior medical staff, physiotherapy and nursing staff reported
      that multiprofessional communication had improved, resulting in identification
      and treatment of critically ill patients. The authors suggest that the Amber
      Project, which incorporates the use of a "track and trigger" warning system, has
      been an effective initiative in identifying patients at risk of developing
      critical illness on general wards. Its positive impact on the performance and
      confidence of qualified nurses working in difficult environments has resulted in
      the extension of the project to all other wards in the hospital.

PMID- 15580087
TI  - Nurse who put patients at risk by performing poor nursing practices.

PMID- 15580088
TI  - The complexities of perioperative blood transfusion in Ireland.
AB  - Issues surrounding blood and blood products are important considerations of
      patient care in Irish society. Consequently, political, socio-economic, cultural
      and ethicolegal issues, together with technological and pharmacological advances
      in new transfusion therapies, are important considerations while caring for
      clients across all areas of health care. Patient autonomy is proliferating and
      perioperative nurses have a duty of care to patients to provide information
      regarding impending surgery and available alternative treatments. This article
      will focus on issues surrounding blood and blood products in relation to
      perioperative nursing practice.

PMID- 15580089
TI  - Nutrition 2: a vital consideration in the management of skin wounds.
AB  - The first part of this review focused on the essential biological features of
      human skin, their origins and cellular relationships as a basis for understanding
      nutritional requirements in health and disease (see Vol 13 (19; Tissue Viabil
      Suppl): S22-S28). The second part will discuss the importance of a good, well
      balanced diet sufficient in proteins (amino acids), fats, carbohydrates, vitamins
      and minerals in the management of skin wounds. Evidence is drawn from clinical
      trials, case studies of patients with known genetic deficiencies affecting
      dietary metabolism and metabolic studies. Experimental studies in laboratory
      animals have provided limited information on the role of nutrient deficiencies in
      wound repair. There is still an urgent need for prospective controlled studies on
      the importance of key nutrients at principle phases in the wound-healing cascade
      and how uptake and metabolism is regulated by growth factors, cytokines and
      hormones.

PMID- 15580090
TI  - The coroner's jurisdiction 2: the current law in the UK.

PMID- 15580091
TI  - The issues for nurses involved in implementing evidence in practice.
AB  - Evidence-based practice (EBP) is currently high on political and professional
      agendas. However, there is a suggestion that despite apparent enthusiasm for EBP,
      it is not becoming a reality. A variety of reasons for evidence not being
      implemented in practice exist, including the way in which evidence is
      communicated, how staff are involved in changes in practice, the availability of
      resources, patient expectations and the priority afforded to EBP by individuals
      and organizations. These issues must be addressed if EBP is to succeed.

PMID- 15580092
TI  - A static-led approach to pressure ulcers: an evaluation after 3 years.
AB  - Pressure damage has high cost implications to the patient and care providers. The
      choice of appropriate equipment to help in the prevention of tissue damage is
      hampered by extensive choice and little guidance on the most effective product to
      use. The static-led approach was introduced into Carmarthenshire NHS Trust 3
      years ago. This approach simplified the choice of equipment, improving the
      appropriate usage and reducing expenditure. This article aims to evaluate the
      approach 3 years after its introduction to determine if the benefits to the
      patient and the organization still apply.

PMID- 15580093
TI  - Patient assessment: a key requirement of nursing care.

PMID- 15580094
TI  - From abstraction to reality: changes in primary care.

PMID- 15580095
TI  - Looking over the new primary care landscape.

PMID- 15580096
TI  - Nutritional screening in the community: developing strategies.
AB  - Malnutrition is a significant clinical and public health problem in the community
      with the wider determinants of health including poverty, social isolation and
      deprivation all exacerbating its incidence. It is frequently undetected and
      untreated. Effective nutritional screening is needed to reduce the prevalence of
      malnutrition but barriers to implementation do exist. Working with staff to
      identify barriers that prevent the effective adoption of nutritional screening is
      key to ensuring that appropriate nutritional action always occurs in a timely
      manner. Profiling the local community helps to give a clearer overview of the
      high-risk population groups and provides robust evidence which helps the process
      of identifying priorities for action.

PMID- 15580097
TI  - Tap water or normal saline for cleansing traumatic wounds?
AB  - The aim of this review was to identify whether cleansing with tap water results
      in higher rates of wound infection or delayed healing compared with other
      cleansing solutions in adults or children with acute uncomplicated traumatic soft
      tissue wounds. The review utilized a systematic search of key databases (Cochrane
      Library, Medline, Embase, Cinahl, British Nursing Index and PubMed),
      bibliographies, and internet resources. Three controlled trials were found which
      studied 1281 people. One further study reported outcomes but could not be fully
      examined as only an abstract was available. Based on the studies reviewed,
      results suggest no clinically significant increase in the risk of wound infection
      in wounds irrigated with tap water when compared to sterile normal saline in
      uncomplicated soft tissue injury. However, the available evidence lacks strength
      because of the relatively low power and poor quality of studies.

PMID- 15580098
TI  - What's on the Agenda for Change?
AB  - With the imminent roll-out of "Agenda for Change", most nurses will be busy
      checking their job profiles and ensuring they get the most out of the process. In
      this article, Yvonne Savage provides a timely overview of what all this effort
      will mean in the longer term.

PMID- 15580099
TI  - Urostomy products: an update of recent developments.
AB  - This article provides an overview of the recent developments in appliances for
      people with a urostomy. Following a short background, the products that may be
      useful for this patient group are discussed.

PMID- 15580100
TI  - Living wills, duty of care and the right to treatment.
AB  - CASE STUDY: Agnes Simon, a district nurse with 20 years' experience, has been
      caring for a man with motor neurone disease for the last 5 years. During this
      time the patient has shown remarkable tenacity but the disease has now progressed
      to the stage where artificial nutrition and hydration (ANH) is required. A
      percutaneous endoscopic gastrostomy tube has been inserted through which the
      patient receives food, water and medication. On her most recent visit the patient
      gave Agnes a signed and witnessed living will. Unusually, the living will did not
      indicate the patient's wishes regarding the limitation of treatment. Instead it
      made clear that the patient wished to continue to receive ANH up to the time of
      his death. He did not want the care team to withdraw this treatment without his
      permission, as he feared he would suffer from the indignity of slowly dying from
      thirst and starvation. Agnes has never seen a living will where a patient demands
      a right to treatment and wonders whether such a document is lawful and binding on
      her.

PMID- 15580101
TI  - Assessing for depression and mood disturbance in later life.
AB  - Depression has been identified as a common mental disorder in old age but
      frequently remains undetected. The Geriatric Depression Scale is one of the most
      heavily promoted scales for the screening of older people. Short versions of the
      scale (GDS-15 and GDS-4) are recommended for use with community patients, though
      most of the validation studies have been with people attending GP surgeries and
      outpatient departments. Changing the threshold affects the sensitivity and
      specificity of the scale and it has been recommended that the cut-off points
      should be lower when the tool is used in clinical practice and higher when used
      for research purposes.

PMID- 15580102
TI  - Converting people with type 2 diabetes to insulin.
AB  - Type 2 diabetes has commonly been viewed as more benign than type 1, partly
      because it was once rare to use insulin in its management. With the recognition
      of the importance of tight control of blood glucose, it is now the case that most
      people with type 2 diabetes will require insulin at some point. This article
      discusses the reasons why insulin treatment should be used in type 2 diabetes,
      and some of the practicalities of insulin initiation and management.

PMID- 15580103
TI  - A personal and professional drive to implement joined-up services. Interview by
      Tom Pollard.

PMID- 15580104
TI  - The Peristeen Anal Plug: a modern solution for an embarrassing problem.
AB  - Faecal incontinence is a problem that affects over 500,000 people in the UK, but
      unlike urinary incontinence is rarely spoken about or adequately addressed. The
      problem may arise from a range of causes, including obstetric trauma, surgery and
      neurological disorders. Like urinary incontinence, faecal incontinence can be
      managed. This article discusses one management option--the Peristeen Anal Plug-
      and illustrates with case histories the beneficial effect proper management of
      faecal incontinence can have on patients' lives.

PMID- 15580105
TI  - Recruiting and retaining primary care nurses.

PMID- 15580106
TI  - The existential slap--a crisis of disclosure.

PMID- 15580107
TI  - Reflections on clinical audit in palliative care following an attempt to audit
      urinary catheterization.
AB  - Audit has a high profile within palliative care quality initiatives. However,
      there are numerous potential pitfalls to auditing. We had hoped to perform a
      multicentred multiprofessional audit on urinary catheterization of hospice
      patients. Unexpectedly, the problems encountered highlighted numerous flaws in
      our approach to audit. An initial standard-setting pilot study, using a
      prospective observational methodology, generated results for 25 patients. The
      audit cycle was not pursued, as the data and the process did not appear valid.
      Conversely there were valuable lessons from reflecting on our mistakes and
      reviewing historical 'wisdom'. For example, audit's interface with research can
      easily be misunderstood and the difficulties of audit in palliative care can be
      underestimated. Particularly concerning was the potential for harm from
      insufficient rigour within audit processes, in allowing invalid data to influence
      practice. Conversely, despite risks, robust studies within audit may inform the
      limited palliative care research base.

PMID- 15580108
TI  - The use of personalized poems in palliative care: one Japanese health
      professional's experience.

PMID- 15580109
TI  - A personal reflection on sitting at the bedside of a dying loved one: the vigil.
AB  - This article presents a personal reflection of the dynamics and phenomena that
      occurred during a 3-day vigil at the bedside of a loved one. This piece reports
      on the interactions between the patient, family members and staff and refutes, in
      this instance, the notion that dying in hospital is not a family affair. This
      reflection shares the experiences of one family and highlights the importance of
      communication among family members and also between family and staff. The article
      suggests a number of lessons for practitioners.

PMID- 15580110
TI  - Group supervision to support competency development in palliative care in Norway.
AB  - AIM: to develop and evaluate a model of supervision created to provide continuous
      support throughout a 2-year postgraduate education programme. METHODS: twenty
      five students attending the first 2-year postgraduate course in palliative care
      at the University College, Buskerud, Norway took part in a prospective study. A
      questionnaire was administered on five occasions: on commencement of studies,
      after 6 months, 12 months, 18 months and at the end of the programme. Student
      statements were analysed using methods of qualitative content analysis. RESULTS:
      students' appreciation of the value of supervision increased from the first to
      the last recording. Reflection and dynamic dialogue during group supervision were
      reported to be well-suited as methods of support in the development of insight
      into palliative care, integration of theory and practice, and development of
      skills. CONCLUSION: students stated that supervision confirmed knowledge, gave
      meaning and increased self-awareness in palliative care.

PMID- 15580111
TI  - Handling spiritual questions of terminally ill patients.

PMID- 15580112
TI  - UK forum annual conference: supporting palliative care around the world.

PMID- 15580113
TI  - Consensus statement on antimicrobial treatment of odontogenic bacterial
      infections.
AB  - The infection of the oral cavity is a common public health problem and constant
      cause for antibiotic prescription, with 10% of antibiotics used to treat this
      problem. However, few studies have so far aimed to determine its incidence. Added
      to this, its relationship with certain sytemic diseases (cardiac, endocrine, etc)
      confers this pathology vital importance. In spite of the frequency and importance
      of odontogenic infection, the current dispersion in criteria regarding key
      aspects in classification, terminology and therapeutic recommendations is
      noticeable. The main objective of this document, compiled as a consensus
      statement by specialists in microbiology and odontology, is to establish useful
      recommendations for all of those involved in the clinical management of this
      pathology. Special attention has been placed on the rise in bacterial resistance
      observed over the last years, specifically the proliferation of betalactamase
      producing strains. Another important factor causing the resistance to appear is
      lack of therapeutic compliance, specially what regards dosage and treatment
      duration. Therefore, this pathology constitutes a complex problem which requires
      the instauration of broad spectrum antimicrobials, well tolerated and a
      convenient posology so that patients receive the adequate dose over the necessary
      period. High doses of amoxicillin/clavulanate (2000 mg/125 mg) have showed good
      results and power to overcome resistance. Other agents such as metronidazole and
      clindamycin, followed by de claritromycin and azithromycin have also proved to be
      active against most of microorganisms responsible for odontogenic infection.

PMID- 15580114
TI  - Oral cancer risk and molecular markers.
AB  - The clinical appearance and, especially, the degree of dysplasia that may be
      shown by pre-cancerous lesions in the oral cavity suggest a potential for
      malignisation. An increasing number of studies are seeking new, more specific
      markers that would help to determine the degree of cell alteration and enable a
      better understanding of the degree of malignant degeneration of these cells. The
      present review considers the most recent findings for these markers, grouping
      them into families: tumour growth markers; markers of tumour suppression and anti
      tumour response; angiogenesis markers; markers of tumour invasion and metastatic
      potential; cell surface markers; intracellular markers; markers derived from
      arachidonic acid; and enzymatic markers.

PMID- 15580115
TI  - Tooth agenesis: in search of mutations behind failed dental development.
AB  - Tooth agenesis are the most common craniofacial malformations. Its prevalence in
      permanent dentition reaches 20% and its expressivity ranges from only one tooth,
      usually a third molar, to the whole dentition. Genetic linkage and molecular
      biology studies have allowed, in the last decade, the identification of mutations
      responsible for some patterns of syndromic and nonsyndromic tooth agenesis. The
      mutated genes are key genes for the development of dentition, like the ones that
      encode the transcription factors MSX1, PAX9 and PITX2, the signalling protein EDA
      and its receptor EDAR. Current research would lead to the development of new
      classifications of tooth agenesis that took into account both the phenotypes and
      the genetic background. This would allow an early diagnosis of the condition,
      before the development of the somatic defect, that could eventually be repaired
      with gene therapy or tissue and organ engineering.

PMID- 15580116
TI  - Gingivitis and anti-neutrophil cytoplasmic antibodies in children and adolescents
      suffering from Leukemia.
AB  - INTRODUCTION: Systemic sickness can originate and proliferate alterations in the
      periodontium. The presence of Anti-neutrophil Cytoplasmic Antibodies (ANCA) in
      patients suffering destructive periodontal disease and systemic illness has been
      widely proven. OBJECTIVE: To determine the existent relation between gingivitis
      and ANCA in children and adolescents suffering from leukemia. These patients were
      examined at the Autonomous Services of the University Hospital in Maracaibo,
      Venezuela, and at the Hospital of Pediatrics Foundation in Zulia State,
      Venezuela. MATERIALS AND METHODS: 40 patients ranging from 6 to 16 years of age
      were included in a controlled study. 20 patients suffering from acute leukemia
      constituted an experimental group, and 20 more patients without apparent systemic
      sickness who formed a control group. All 40 patients underwent clinical
      evaluation, and periodontal tissue radiographic evaluation and assessment of ANCA
      through an enzyme-linked immunoasorbent assay (ELISA); this was done using an
      IMMCO Diagnostic commercial kit. RESULTS: No Significant differences in the
      gingivitis average index, plaque and bone loss between the experimental and the
      control group were evidenced. A significant correlation between gingivitis and
      ANCA was not evidenced either. Nevertheless, 7 out of 20 patients of the
      experimental group turned out to be ANCA positive. In contrast, no positive cases
      were reported in the control group. (p < 0.05 Fisher Test). CONCLUSION: The
      results of this study suggest that the presence of ANCA is probably related to
      ongoing immune alterations in patients suffering from leukemia but not related to
      gingivitis.

PMID- 15580117
TI  - Frequency of supernumerary teeth in Mexican population.
AB  - Supernumerary teeth (ST) are a not uncommon developmental anomaly which appears
      in 0.3 to 3.8 percent of the population. We studied the corresponding radiographs
      from 2241 patients, both sexes who seeked dental attention at the Outpatient
      Clinic of the Division de Estudios de Posgrado e Investigacion, Facultad de
      Odontologia, UNAM in Mexico City. Of them, we found 72 patients (3.2%) with 102
      ST. Of the 72 patients, 39 were males (54.2%) and 33 females (45.8%). Mesiodens
      was the most common ST (48.6%), followed by supernumerary premolars (26.4%),
      supernumerary laterals (11.1%) and fourth molars (9.7%). This series includes
      cases with one, two and three ST and one case comprising 10 ST. Our results
      suggest that frequency of ST in the population studied differs in some aspects
      with previously reported series and that frequency of ST shows different rates
      depending the population studied. As our results demonstrate, it is encouraged
      the need to have panoramic radiographs of all patients attended in dental
      offices, clinics and schools of Dentistry in order to detect and diagnose
      undiscovered pathologies.

PMID- 15580118
TI  - Oral manifestations of HIV infection in infants: a review article.
AB  - The vast majority of children with HIV infection present oral manifestations
      among the first signs of illness. These lesions are not produced directly by the
      virus, but are manifestations associated with HIV infection, and are not
      pathognomic of the infection itself. Some of these oral lesions have a prognostic
      value with regard to progression of the infection and the appearance of AIDS;
      independently of other, more commonly used markers. The essential risk factors
      that influence the development of such oral manifestations are the low number of
      CD4+ lymphocytes, xerostomia, and the lack of anti-retroviral therapy.
      Opportunist infections, such as mycoses -- including pseudomembranous oral
      candidiasis, are found with higher frequency; followed by the herpetic viral
      infections. The oral lesions that appear in infected children differ in
      prevalence from those found in seropositive adults, some, such as parotid
      hypertrophy, present more exclusively in children, others, such as periodontal
      bacterial infections and Kaposi's Sarcoma, are lesions that predominate in the
      adult HIV-infected population. Given the current impact of the pandemic caused by
      HIV, it is the responsibility of dental professionals to prevent, detect, treat
      and control the oral lesions in those patients infected with HIV. All of which
      will be reflected in a reduction in transmission, lower mortality and greater
      long-term survival for infected children.

PMID- 15580119
TI  - Lichenoid reaction associated to amalgam restoration.
AB  - Hypersensitivity to mercury associated with amalgam restorations may occur and
      present in one of two different ways. Most commonly it presents as an oral
      lichenoid reaction affecting oral mucosa in direct contact with an amalgam
      restoration and represents a delayed, type IV, cell mediated immune response to
      mercury or one of the other constituents of the dental amalgam. We report a case
      of oral lichenoid reaction associated to amalgam restoration. A 38 year-old woman
      presented a caries lesion of tooth #37. A Blacks class I preparation was
      performed and filled with amalgam. After 19 months, intra-oral examination
      revealed atrophic lesion, lightly erythematous, affecting the left buccal mucous.
      The lesion contacted directly with the amalgam restoration in the lower first
      molar. The right buccal mucosa was normal. His medical history was unremarkable,
      he was taking no medication and had no known allergies. However, the patient had
      felt certain rare sensation in that zone when eating sharp meals. Biopsy showed
      histological changes compatible with oral lichen planus. The patient decided not
      to change again the restoration, because she did not have important annoyances
      and she did not wish to be treated again. Other restorations were performed with
      composite resins, and no reaction was evidenced in the mucosa.

PMID- 15580120
TI  - Miescher's cheilitis granulomatosa. A presentation of five cases.
AB  - Miescher's cheilitis granulomatosa (CG) consists of the appearance of recurrent
      labial edema on one or both lips, which can become persistent. It has
      traditionally been considered as a monosymptomatic form of the Melkersson
      Rosenthal syndrome, described as the association of recurrent labial and/or
      recurrent facial edema, relapsing facial paralysis and fissured tongue. The aim
      of this study is to present a series of five clinically and histopathologically
      diagnosed cases of CG that came to our clinic at the Teaching Unit of Oral
      Medicine, Faculty of Medicine and Odontology, University of Murcia. A complete
      study of these patients evaluated the age, sex, family history, and location and
      course of the signs and symptoms. Various complementary examinations were carried
      out, studying the hematic characteristics (hemogram, erythrocyte sedimentation
      rate, leukocyte count), including immunological and histopathological studies.
      The treatment consisted of intralesional corticoids, combined in some cases with
      anti-leprous drugs or systemic corticoids. A good response to treatment was
      obtained in all cases.

PMID- 15580121
TI  - Lesions of the oral mucosa and periodontal disease behavior in pregnant patients.
AB  - AIMS: A study is made to contrast the prevalence and severity of periodontal
      disease, the needs for periodontal treatment, and the prevalence of lesions of
      the oral mucosa in pregnant (study group) and non-pregnant women. STUDY DESIGN:
      During the period 1991-1999, a prospective observational study was made of 7952
      women seen in the Dental School of De La Salle Bajio University (Leon, Gto.
      Mexico). The following variables were documented: age, disease antecedents,
      simplified periodontal index, and lesions of the oral mucosa. Two patient groups
      were defined: pregnant and non-pregnant women exhibiting a similar age
      distribution. The data were presented as percentages, and comparisons were made
      based on the chi-square test. RESULTS: Pregnancy was not found to be a decisive
      factor for the development of periodontal disease, no differences in the
      prevalence of gingivitis (54.54 and 50.50%) and periodontitis (31.82 and 31.75%)
      being observed between the two groups. However, the severity of periodontitis was
      significantly greater among the pregnant women (18.18% versus 9.88%; p< 0.01).
      The prevalence of oral mucosal lesions was similar in both groups (30%), 13
      lesions being identified in the study group, with a predominance of leukoedema,
      traumatic ulceration, red traumatic lesions, benign migratory glossitis
      (geographic tongue), irritative keratosis and pyogenic granuloma. The non
      pregnant women in turn exhibited 57 lesions. Pyogenic granuloma and benign
      migratory glossitis exhibited significant differences between the two groups (p<
      0.005). CONCLUSIONS: Gingivitis and periodontitis showed similar prevalences in
      pregnant and non-pregnant women, though severe periodontitis was more frequent
      among the former. Pyogenic granuloma and benign migratory glossitis were the
      lesions with the greatest prevalences during pregnancy.

PMID- 15580122
TI  - Local anesthetics in dentistry.
AB  - The purpose of the present paper is to carry out a review of the literature on
      local anesthetics (LAs), which are the most commonly used drugs in dentistry.
      Thanks to their improvement over the last few years, they have constituted an
      enormous advance in both odontological treatment -- improving the dental
      operation in a determinant manner, and the comfort of the patient during these
      procedures. Furthermore, the addition of a blood vessel constrictor to these
      local anesthetics has meant that a lower dose of anesthetic can be used, which at
      the same time acts for longer, providing better conditions for both the patient
      and dentist. In addition, a study is made of the possible drug interactions,
      contraindications etc. of the different components in the anesthetic solution,
      and likewise the possible allergic hypersensitive reactions which can take place
      and which must be taken closely into consideration when used in the oral cavity.

PMID- 15580123
TI  - Analgesic efficacy of diclofenac sodium versus ibuprofen following surgical
      extraction of impacted lower third molars.
AB  - OBJECTIVE: An evaluation is made of the analgesic efficacy of diclofenac sodium
      versus ibuprofen after impacted lower third molar surgery. STUDY DESIGN: The
      patients were randomly assigned to one of two groups (ibuprofen or diclofenac).
      The difficulty of third molar surgery, performed under local anesthesia, was
      assessed by the degree of inclusion involved. The recorded study variables were
      pain intensity and the need for rescue medication during one week. The recordings
      were made once a day at the same time, using a patient-completed questionnaire.
      RESULTS: Eighty-one patients were finally included in the study (87.1%). The
      results were similar in the first 48 postoperative hours in both groups, though
      on the third day the diclofenac group tended to show higher pain scores--the
      differences being nonsignificant, however (p<0.05). This tendency was also
      reflected by an increased need for rescue medication and the consumption of a
      larger number of tablets in the diclofenac group. CONCLUSIONS: There were no
      statistically significant differences in analgesic efficacy between diclofenac
      sodium and ibuprofen, though the former was associated with an increased need for
      supplementary medication in the first two postoperative days (p<0.05).

PMID- 15580124
TI  - Juvenile ossifying fibroma: a case study.
AB  - We present the case of an 8-year-old patient with a juvenile ossifying fibroma in
      the right mandibular angle and a radicular cyst in the left mandibular angle,
      which produced a major swelling at the level of the mandibular angles and
      prevented the correct eruption of the lower first molars. After the clinical and
      radiological (panoramic X-ray and dental scan of the mandible), the corresponding
      surgical treatment (cystectomy and remodelling) and histopathological study were
      carried out. Although juvenile ossifying fibroma is an uncommon clinical entity,
      its aggressive local behaviour and high recurrence rate mean that it is important
      to make an early diagnosis, apply the appropriate treatment and, especially,
      follow the patient up over the long term.

PMID- 15580125
TI  - Primary malt lymphoma of the tongue.
AB  - Primitive malignant lymphoma mucosa associated lymphoid tissue (MALT) on the
      tongue are rare entities. We report here a case of an old woman (80 years old)
      with a tumor in the dorsum of the tongue, which was histologically diagnosed as
      an extra-nodal marginal B cell lymphoma. An inflammatory reaction resembling
      myoepithelial sialoadenitis was observed in the minor salivary glands adjacent at
      the tumour, suggesting a possible derivation of the lymphoma from a previous
      reactive process of unknown origin.

PMID- 15580126
TI  - Fine-needle aspiration cytology in the diagnosis of cervicofacial actinomycosis:
      report of 15 cases.
AB  - OBJECTIVES: Actinomycosis is quite an infrequent bacterial infection nowadays.
      However it can be considered in cases with a persistent cervicofacial disease.
      Although it is a bacterial infection, microbiologic cultures are frequently not
      diagnoses, therefore histopathologic studies and image studies are essential. Our
      interest is to explain our experience with cervicofacial actinomycosis; the
      clinical behaviour, evolution and treatment, always assisted by their elected
      diagnostic technique: the FNAC. STUDY DESIGN: In the last 16 years, 15 patients
      have been diagnosed with cervicofacial actinomycosis by FNAC, treated by
      Maxillofacial, Internal Medicine and Paediatrics units. Clinical course,
      evolution, anatomical space situation, antibiotic treatment, and surgical
      treatment have been studied. RESULTS AND CONCLUSIONS: The fine-needle aspiration
      cytology (FNAC) is an easy, safe and rapid method, with a high effect, that has
      made the final diagnosis in 15 cases in our Hospital. All the patients have had a
      good clinical evolution, only in one case did we need a new treatment for
      recidive. In all the cases treatment has been definitive. Our interest is to
      explain our experience in the treatment of cervicofacial actinomycosis, its
      clinical presentation and evolution, together with its elected method of
      diagnosis, FNAC.

PMID- 15580127
TI  - Oral flora in the age of molecular biology.
AB  - The present work describes the fundamental aspects of the molecular methods that
      are applied to oral microbiology: probes, PCR, multiple real time PCR, 16S rDNA,
      and proteomics. Likewise, it presents the results obtained by applying these
      methods to the study of the bacterial flora encountered inside the mouth. By
      identifying 16S rDNA, up to 132 known species and 215 new, unknown phylotypes
      have been detected inside patients s periodontal pockets. We are currently using
      a commercial system based on multiple PCR (genomic amplification), followed by
      reverse hybridization to detect the five species known to cause periodontal
      disease. We also summarize the findings derived from the application of proteomic
      techniques to the study of odontologic infections pathogenesis and from the use
      of molecular methods in the study of resistance to antimicrobial agents. Finally,
      it puts forth the problems that remain unsolved with respect to oral flora and
      the treatment of odontogenic infections. Traditional culture methods continue to
      be indispensable, as they make it possible to later work with the cultured
      microorganisms.

PMID- 15580128
TI  - Necrotising periodontal diseases.
AB  - Necrotizing gingivitis (NG) or necrotising ulcerative gingivitis (NUG) is
      considered to be an acute opportunistic gingival infection caused by bacterial
      plaque. It appears more frequently in undernurished children and young adults as
      well as patients with immunodeficiency. In its pathogenesis, there are factors
      related to the oral microbiota with invasion processes on the one hand, and on
      the other hand, factors associated with the host, such as signs of capillary and
      immunological disorders as well as undernurishment. The disease is characterized
      by pain, bleeding and papillary necrosis with tendency to relapse. Diagnosis is
      made by a simple clinical examination. However, complementary tests ought to be
      performed in order to eliminate the possibility of illnesses systemic or
      immunodeficiency. Early and sustained treatment is strongly recommended. Lesions
      of the gums (craters in the interdental papillae) as an aftermath of the disease
      is a possibility, or if there is necrotizing periodontitis there will be loss of
      attachment tissue.

PMID- 15580129
TI  - Microbiological basis of oral infections and sensitivity to antibiotics.
AB  - Because oral infections are common, the physician must understand the underlying
      etiology, pathogeny, and other variables that determine how these processes
      evolve in order to choose the most appropriate antibiotic drug. The special
      characteristics of the oral cavity determine the make-up of the microflora that
      lives there. Different anaerobic species belonging to the Peptostreptococcus,
      Prevotella, Fusobacterium, Gemella, and Porphyromonas genera are of particular
      interest, as are the aerobic species Streptococcus, Staphylococcus, and
      Corynebacterium. Each of these microorganisms occupies a different microniche
      within the oral cavity, and the prevailing balance is upset when conditions
      become modified as a result of illness or due to dental interventions such as
      tooth extraction or tooth scaling and polishing. Pathogenic or opportunistic
      bacteria (Actinomyces, Prevotella intermedia species, etc.) can develop in these
      conditions, as can yeasts (Candida sp., Histoplasma capsulatum), virus (herpes
      simplex, papilomavirus), and parasites (Entamoeba gingivalis, Trichomonas tenax).
      When infection occurs, the patients s immune system reacts by means of inborn
      immunity (non-specific) and acquired immunity (specific). Empirical treatment is
      administered that should be based on etiological data and on the antimicrobial
      sensitivity of the pathogen that is causing the infection. However, oral
      microflora sensitivity to different antibiotics is currently declining and there
      is a noticeable trend towards resistances. As a consequence of all this, the
      treatment of oral infections must also aim to restore the ecological balance of
      the oral cavity and to minimize the emergence of resistance in the microorganisms
      present in the mouth. Hence, epidemiological oral pathogen sensitivity studies
      must be conducted, fostering the administration of appropriate antibiotics at
      proper doses and keeping specialists abreast of the latest trends. In recent
      decades, oral infections comprise one of the most common pathologies in the
      general population, due in large part to infectious complications associated with
      poor oral hygiene. This in turn, translates into an increased need and demand for
      dental care, while at the same time, it requires that the professional accurately
      understand the etiological factors involved, as well as the pathogeny and
      different variables that determine the specificity of these kinds of infections,
      so as to be able to choose the appropriate antimicrobial drugs for proper
      treatment.

PMID- 15580130
TI  - Third molar infections.
AB  - Pericoronitis is an infectious disease often associated with the eruption of a
      third molar. It can be either acute (serous and suppurative) or chronic. Pain is
      usually the predominant symptom in acute stages, whereas chronic forms of the
      disease may display very few symptoms. Both present exudate. The infection is
      multimicrobial, predominantly caused strictly by betalactamase-producing
      anaerobeic microorganisms. Treatment measures are symptomatic, antimicrobial and
      surgical. Antimicrobial treatment is indicated for preoperative prophylaxis when
      there is a high risk of postoperative infection and, during the acute stages of
      suppurative pericoronitis when surgery must be postponed. First-line treatment in
      this case consists of amoxicillin with associated clavulanic acid. Although
      surgical treatment of pericoronitis presenting at the third molar is indicated as
      a Grade C recommendation for extraction, it is the most common indication for
      extraction of a retained third molar, owing to the improved quality of life it
      can offer the patient.

PMID- 15580131
TI  - Maxillofacial cellulitis.
AB  - Of all infections associated to oral pathology, the most relevant ones are those
      that are related to dental pathology. Cellulitis is an infection of the cellular
      adipose tissue located in the aponeurotic spaces. It can be classified on the
      basis of location, severity and evolution. The aponeurotic compartments that
      allow odontogenic infections to spread have been categorised as: superficial
      compartment, floor of the mouth, masticator compartment, parapharyngeal space,
      parotid space and paratonsillar space. The present work describes the anatomical
      structures that comprise these spaces. The clinical forms of facial cellulitis
      are divided into acute and chronic. Potential complications consist of orbital
      infections, necrotising fascitis, thrombosis of the cavernous sinus, cerebral
      abscess and mediastinitis. Diagnosis is made on the basis of anamnesis, physical
      examination and complementary procedures (analytical tests and imaging studies).
      Treatment includes: treatment of causes (depending on the underlying cause in
      each case), incision and drainage, antibiotic therapy (chosen empirically) and
      complementary medical care. Odontogenic infections are primarily treated with
      surgery and coadjuvant antibiotic therapy.

PMID- 15580132
TI  - Odontogenic infections. Complications. Systemic manifestations.
AB  - The term, odontogenic infection refers to an infection that originates in the
      tooth proper or in the tissues that closely surround it; said infection then
      progresses along the periodontia down to the apex, involving periapical bone and
      from this area, it then spreads through the bone and periosteum towards near-by
      or more distant structures. The relevance of this type of infection lies in that
      it can cause infections that compromise more distant structures (via direct
      spread and distant spread), for example, intracraneal, retropharyngeal and
      pulmonary pleural infections. Dissemination by means of the bloodstream can lead
      to rheumatic problems and deposits on the valves of the heart (endocarditis),
      etc. The conditions or factors that influence the spread of infection are
      dependent on the balance between patient-related conditions and microorganism
      related conditions. The virulence of the affecting germs is dependent upon their
      quality and quantity and is one of the microbiological conditions that influences
      the infection. It is this virulence that promotes infectious invasion and the
      deleterious effects the microbe will have on the host. Patient-related conditions
      include certain systemic factors that determine host resistance, which may be
      impaired in situations such as immunodeficiency syndrome or in brittle diabetes,
      as well as local factors that will also exert their impact on the spread of the
      infection.

PMID- 15580133
TI  - Acquired immunodeficiency syndrome: manifestations in the oral cavity.
AB  - Human immunodeficiency virus (HIV) infection is a pandemic disease characterised
      by impairment of the immune system; the main parameter is a progressive decline
      in the number of CD4 lymphocytes. This circumstance paves the way for
      opportunistic infections and the development of neoplastic processes that can
      lead the patient to a state known as acquired immunodeficiency syndrome (AIDS)
      and ultimately, results in death. The incorporation of treatment based on a
      cocktail of different active drugs (highly active antiretroviral therapy) has
      made it possible to drastically change the panorama of the disease in developed
      nations; improving quality of life for the patient and delaying the progression
      of the disease. The oral manifestations of HIV infection have been and continue
      to be an important component of the disease from the very first descriptions and
      are indicative of progression. At some point in the course of the disease, nine
      out of every ten patients will present oral manifestations and, on occasion,
      these symptoms will be the first sign of the syndrome. It is essential that oral
      healthcare professionals recognize the hallmarks of the illness. In developed
      countries, the emergence of new therapies has made it possible to significantly
      reduce immune deficiency-related oral manifestations, both in terms of frequency,
      as well as severity. This review analyses the most important oral lesions
      associated with HIV infection and the current state of affairs in this regard.

PMID- 15580134
TI  - Treatment options in odontogenic infection.
AB  - Most infections of the oral cavity are primary, odontogenic infections, with
      dental caries, gingivitis, and periodontitis the most common. Treating these
      infections will encompass odontologic, antimicrobial, surgical or combined
      treatment. Antimicrobial treatment includes the use of betalactams, macrolydes,
      tetracyclins, metronidazole, clindamycin, or combined treatment. The most
      commonly used ones are administered orally. PK/ PD parameters predict THE
      clinical and microbiological efficacy of the antibiotic. The three indices that
      are generally used to measure clinical efficacy are: T >MIC (time during which
      the concentration is above the minimum inhibitory concentration), Cmax/ MIC
      (ratio between peak concentration and the minimum inhibitory concentration) and
      AUC/ MIC (ratio between the area under the curve and the minimum inhibitory
      concentration). Amoxicillin/ clavulanic acid is one of the antibiotics
      recommended for the treatment of odontogenic infections due to its wide spectrum,
      low incidence of resistance, pharmacokinetic profile, tolerance and dosage.

PMID- 15580135
TI  - Bacterial infections of pulp and periodontal origin.
AB  - The anatomical and structural characteristics of the pulp make this structure
      prone to altering as a result of, for instance, periodontal conditions
      (proximity), iatrogenic alterations, infections and involvement of vascular and
      nerve structures (it is surrounded by hard tissues that prevent expansion), to
      name just a few. Pulpitis is a process that courses with pain of varying
      intensity that allows us to determine the location of the lesion in clinical
      terms. Its evolution varies and may even progress to pulpar necrosis that in
      turn, produces neuritis-like pain. Diagnosis is established by means of clinical
      symptomatology and supported by X-rays, palpation of tissues at painful sites,
      application of electrical stimuli, heat, etc. Periodontitis is a bacterial
      infection originating in the apex. The most important form is the so-called acute
      apical periodontitis that arises as a result of a prior episode of pulpitis. It
      is characterized by acute pain located in the tooth, accompanied by the feeling
      of having a long-tooth. The patient refers being unable to chew on that side;
      there may be painful mobility of the tooth and an outflow of pus that alleviates
      symptoms. X-rays do not provide a lot of information, but may attest to a
      widening of the apical space. This pathology may disseminate to surrounding
      tissues, leading to conditions of considerable severity.

PMID- 15580136
TI  - Bacterial endocarditis prophylaxis.
AB  - Bacterial endocarditis (BE) is a disease resulting from the association of
      morphological alterations of the heart and bacteraemia originating from different
      sources that at times can be indiscernible (infectious endocarditis). It is
      classified on the basis of the morphological alteration involved, depending on
      the clinical manifestations and course of illness, which varies according to the
      causative microorganism and host conditions (for example, it is characteristic in
      I.V. drug users). The most common microorganisms involved are: Streptococcus
      viridans (55%), Staphylococcus aureus (30%), Enterococcus (6%) and HACEK bacteria
      (corresponding to the initials: Haemophilus, Actinobacillus, Cardiobacterium,
      Eikenella and Kingella), although on occasions it can also be caused by fungi.
      The oral microbiological flora plays a very important role in the
      aetiopathogenesis of BE, given that the condition may be of oral or dental
      origin. This paper will deal with the prevention of said bacteraemia. Prophylaxis
      will be undertaken using amoxicillin or clindamycin according to action
      protocols, with special emphasis placed on oral hygiene in patients with
      structural defects of the heart.

PMID- 15580137
TI  - Aetiology, classification and pathogenesis of pulp and periapical disease.
AB  - At present, the majority of the treatments that are performed in the clinic are
      due to disease entities involving the dental pulp and periapex. Dental pulp is a
      richly vascularized and innervated tissue, enclosed by surrounding tissues that
      are incapable of expanding, such as dentin. It has terminal blood flow and small
      gauge circulatory access the periapex. All of these characteristics severely
      constrain the defensive capacity of the pulp tissue when faced with the different
      aggressions it may be subjected to. Pulp tissue can also be affected by a
      retrograde infection, arising from the secondary canaliculi, from the periodontal
      ligament or from the apex during the course of periodontitis. Due to the fact
      that periapical disease is almost inevitably preceded by pulp disease, we shall
      begin by describing the causes of pulp disease and will then proceed to a
      discussion of the causes of periapical disease. The course of illness and
      classification of these pathological entities will depend on the aetiology
      involved. We will analyse pulp necrosis and pulp degeneration that are capable of
      triggering reversible apical periodontitis or irreversible apical periodontitis.

PMID- 15580138
TI  - Periimplantitis.
AB  - Orodental rehabilitation through the use of implants offers very high success
      rates. In this paper, we describe some of the complications involved with this
      technique, such as periimplant disease and, within this category,
      periimplantitis, an inflammatory reaction in which there is a loss of the bony
      support of the implant accompanied by inflammation. The aetiology of the disease
      is conditioned by the status of the tissue surrounding the implant, implant
      design, degree of roughness, the poor alignment of implant components, external
      morphology and excessive mechanical load. The microorganisms most commonly
      associated with implant failure are spirochetes and mobile forms of Gram-negative
      anaerobes, unless the origin is the result of simple mechanical overload.
      Diagnosis is based on changes of colour in the gum, bleeding and probing depth of
      periimplant pockets, suppuration, x-ray and gradual loss of bone height around
      the tooth. Treatment will differ depending upon whether it is a case of mucositis
      or periimplantitis. Therapeutic objectives focus on correcting technical defects
      by means of surgery and decontamination techniques (abrasion with carbon
      particles, citric acid solution, topical tetracycline application and laser
      surgery). This study also presents a microbiological study of periimplantitis
      conducted by the Barcelona School of Dentistry that determined that the
      antibiotic therapy proven to be most efficacious in the antibiogram was the
      association of amoxycillin and clavulanic acid.

PMID- 15580139
TI  - Periodontal diseases: microbiological considerations.
AB  - The location of plaque-associated gingivitis at the gingival portion of the tooth
      plays an essential role in its genesis. However, at times local and other host
      response modifying factors also have an influence. The pathogeny of periodontitis
      is more complex. The microorganisms that comprise subgingival plaque are capable
      of acting directly on periodontal tissues or of modifying the host response,
      whereas the participation of the plaque per se (normal, decreased, or increased)
      is as decisive as the action of the bacteria themselves in the emergence of the
      disease. Different types of periodontitis are associated with specific
      microorganisms. The most periodontopathogenic are A. actinomycetemcomitans, P.
      gingivalis, and T. forsythensis. Periodontitis as a whole, represent the source
      of complications such as root caries, endoperiodontal processes and periodontal
      abscesses. They are associated with various illnesses such as atherosclerosis,
      diabetes, and respiratory infections, amongst others, as well as pathological
      oral halitosis. The different modalities of PCR are particularly important in the
      microbiological diagnosis of periodontitis, although on the negative side of
      things, it must be pointed out that in vitro sensitivity studies cannot be
      performed using this technique. First line antibiotic treatment of periodontitis
      includes amoxicillin/ clavulanic acid, metronidazole (associated or not with
      amoxicillin) and clindamycin.

PMID- 15580140
TI  - Periodontal diseases as bacterial infection.
AB  - The periodontal disease is conformed by a group of illnesses affecting the gums
      and dental support structures. They are caused by certain bacteria found in the
      bacterial plaque. These bacteria are essential to the onset of illness; however,
      there are predisposing factors in both the host and the microorganisms that will
      have an effect on the pathogenesis of the illness. Periodontopathogenic bacterial
      microbiota is needed, but by itself, it is not enough to cause the illness,
      requiring the presence of a susceptible host. These diseases have been classified
      as gingivitis, when limited to the gums, and periodontitis, when they spread to
      deeper tissues. Classification of periodontal disease has varied over the years.
      The one used in this work was approved at the International Workshop for a
      Classification of Periodontal Diseases and Conditions, held in 1999. This study
      is an overview of the different periodontal disease syndromes. Later, the
      systematic use of antibiotic treatment consisting of amoxicillin, amoxicillin
      clavulanic acid, and metronidazole as first line coadjuvant treatment of these
      illnesses will be reviewed.

PMID- 15580142
TI  - Gastroesophageal reflux disease in the elderly--a prevalent and severe disease.
AB  - Gastroesophageal reflux disease (GERD) is a prevalent problem that has particular
      implications for physicians treating geriatric patients. In elderly patients,
      there are multiple physiologic changes that occur and influence both the
      manifestations and severity of GERD. Elderly patients typically have less severe
      symptoms of GERD, yet they have more severe esophagitis compared to the younger
      patient population. Physicians treating elderly patients with GERD need to
      recognize that these patients require more potent and sustained acid inhibition
      to effectively and consistently achieve optimal clinical outcomes.

PMID- 15580143
TI  - Sleep and gastroesophageal reflux disease: a wake-up call.
AB  - The medical community has mostly ignored the relationship between sleep and
      gastroesophageal reflux (GER), although recent studies have begun to explore the
      connection and suggest possible treatments. These studies have found that the
      relationship is reciprocal; reflux influences sleep and sleep influences reflux.
      It has been found that nighttime GER can result in a number of complications, and
      more generally, lower the quality of life for its sufferers, establishing sleep
      related GER as a more intolerable form of GER. Though some lifestyle
      modifications may help reduce the risk of nighttime reflux, the use of a proton
      pump inhibitor may be a valuable tool in the management of both heartburn and
      nighttime GER.

PMID- 15580144
TI  - Treatment of gastroesophageal reflux disease: defining endpoints that are
      important to patients.
AB  - Patients with gastroesophageal reflux disease (GERD) seek treatment to obtain
      relief of their symptoms. Symptoms are important to patients because they
      interfere with activities of daily living and impair quality of life. Clinical
      trials in GERD have traditionally focused on the healing of erosive esophagitis,
      and symptom endpoints have been relegated to a secondary role. In primary care,
      however, patients typically are treated empirically without definition of the
      presence or absence of esophagitis. Patient-centered endpoints such as complete
      symptom resolution, patient satisfaction, and improvement in quality of life
      therefore provide more meaningful results in the broad population of patients
      with GERD, provided they are coupled with objective data on mucosal healing. This
      article reviews the importance of patient-centered endpoints in the assessment of
      the treatment of GERD and concludes that complete resolution of symptoms is the
      most rigorous endpoint in clinical trials and provides a meaningful endpoint for
      therapy in clinical practice.

PMID- 15580145
TI  - Proton pump inhibitor co-therapy with nonsteroidal anti-inflammatory drugs--nice
      or necessary?
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti
      inflammatory, analgesic, and anti-pyretic effects, whereas low-dose aspirin (also
      an NSAID) is used for cardiovascular prophylaxis. The main concern limiting use
      of these drugs is their gastrointestinal (GI) toxicity. GI side effects include
      ulcers (found at endoscopy in 15%-30% of patients using NSAIDs regularly),
      complications such as upper GI bleeding (annual incidence of 1.0%-1.5%), and
      development of upper GI symptoms such as dyspepsia (occurring in up to 60% of
      patients taking NSAIDs). Histamine-2 receptor antagonists are not effective at
      preventing NSAID-induced gastric ulcers when used at standard doses, although
      they can decrease upper GI symptoms. Misoprostol effectively decreases NSAID
      induced ulcers and GI complications but is used infrequently in the United States
      perhaps because of issues of compliance (multiple daily doses) and side effects
      (eg, diarrhea, dyspepsia). Once-daily proton pump inhibitor (PPI) therapy also
      decreases the development of NSAID-associated ulcers and recurrent NSAID-related
      ulcer complications; it also decreases upper GI symptoms in NSAID users. In
      patients using aspirin, the addition of a cyclooxygenase-2-specific inhibitor
      appears to significantly increase GI risk to the level of a nonselective NSAID;
      aspirin plus a nonselective NSAID appears to increase GI risk still higher.
      Patients taking low-dose aspirin who have risk factors for GI complications
      (including concomitant nonselective NSAID therapy) should receive medical co
      therapy, such as a PPI.

PMID- 15580146
TI  - Effectiveness of proton pump inhibitors: beyond cost.
AB  - As a drug class, proton pump inhibitors are excellent pharmacologic agents for
      the treatment of gastroesophageal reflux disease. All 5 of the agents discussed
      here are exceptionally effective, so much so that cost has often superseded other
      outcome measures as a primary reason for the choice of agent. This article
      reviews other important outcome measures including control of intragastric pH,
      healing, symptom relief, improvement in quality of life, sleep, and increase in
      work productivity in an effort to "move beyond cost" in decision-making related
      to patient care.

PMID- 15580147
TI  - Challenges in Crohn's disease.

PMID- 15580148
TI  - Why do anti-tumor necrosis factor antibodies work in Crohn's disease?
AB  - Anti-tumor necrosis factor (TNF) antibodies are powerful therapeutic agents for
      the treatment of Crohn's disease. TNF has diverse proinflammatory effects within
      the intestinal mucosa and is a pivotal cytokine in the inflammatory cascade.
      Although anti-TNF antibodies exert a variety of anti-inflammatory effects by
      neutralizing the cytokine, these agents vary in their efficacy. Recent data
      suggest that the ability to bind transmembrane TNF is a key property necessary
      for efficacy. Transmembrane binding of TNF effects apoptosis of T cells, thereby
      alleviating a fundamental defect in Crohn's disease in the regulation of T cell
      populations.

PMID- 15580149
TI  - Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease:
      overview of randomized clinical studies.
AB  - The past decade has brought forth a series of novel biologic agents targeting
      tumor necrosis factor (TNF) for the treatment of Crohn's disease. The
      introduction of infliximab has paved the way for additional anti-TNF strategies
      that have the potential to build on that drug's efficacy and safety profile.
      However, the anti-TNF strategies might not have identical efficacy and safety
      profiles and might differ in dosing compared with therapy for rheumatoid
      arthritis. Most recently, adalimumab has been approved by the US Food and Drug
      Administration for the treatment of rheumatoid arthritis and is undergoing
      evaluation in Crohn's disease, with promising initial results. This review
      discusses the results of controlled clinical trials of anti-TNF agents for
      Crohn's disease.

PMID- 15580150
TI  - An historical overview of the treatment of Crohn's disease: why do we need
      biological therapies?
AB  - Crohn's disease is a disabling inflammatory bowel disease that may involve any
      part of the gastrointestinal tract. The disease decreases quality of life and
      leads to complications including stenoses, abscesses, and fistulae necessitating
      repeated surgeries and bowel resections. Until the late 1990s, standard therapies
      included mainly glucocorticosteroids, 5-aminosalicylic acid (5-ASA), antibiotics,
      and to a lesser extent, immunosuppression with azathioprine (AZA)/6
      mercaptopurine (6-MP) or methotrexate. These therapies, especially
      glucocorticosteroids, mainly controlled symptoms without modifying the long-term
      disease course. Glucocorticosteroids also do not induce sustained mucosal
      healing. The lack of healing capacity mirrors the absent long-term efficacy of
      these drugs. Moreover, long-term use of glucocorticosteroids is associated with
      serious and sometimes irreversible side effects. AZA/6-MP are effective disease
      modifying therapies that have been used in patients who are refractory to or
      relapse after steroids. Unfortunately, these agents have yet to have an
      established optimal benefit due to variations in genetically determined
      metabolism. With the advent of biologicals, new treatment aims have been
      advanced, including induction of remission with bowel healing both short term and
      long term, as well as reduction in the rate of complications, surgeries, and
      mortality.

PMID- 15580151
TI  - Serologic markers in inflammatory bowel disease: state of the art.
AB  - A variety of serologic tests are emerging that are relevant to the diagnosis and
      treatment of Crohn's disease and ulcerative colitis. These laboratory tests
      include: anti-neutrophil cytoplasmic antibody with perinuclear staining (pANCA);
      anti-Saccharomyces cerevisiae antibody (ASCA); outer membrane porin C (Omp C);
      and I2 antibody (novel homologue of the bacterial transcription-factor families).
      The potential roles for serologic testing for inflammatory bowel disease (IBD)
      include adjunctive diagnostic testing in patients with known IBD, screening
      testing for IBD in patients with compatible gastrointestinal symptoms, and
      serving as a marker of unique disease course or prediction of response to
      specific treatments. This article reviews the use of pANCA, ASCA, I2, and Omp C
      in patients with IBD.

PMID- 15580152
TI  - Management of ascites in patients with end-stage liver disease.
AB  - Ascites is the most common complication in patients with decompensated cirrhosis.
      Approximately 50% of patients with compensated cirrhosis will develop ascites
      over a 10-year period. This occurrence is an important milestone in the natural
      history of end-stage liver disease because only 50% of patients survive 2 to 5
      years (depending on the cause of cirrhosis) after its onset. Salt restriction and
      diuretics are the mainstays of therapy, and these measures are effective in
      approximately 90% of patients. Large-volume paracentesis or transjugular
      intrahepatic portosystemic shunt can be used in patients with refractory ascites
      as either a bridge to transplant or as palliation. Cirrhotic patients with
      ascites should be carefully monitored for the development of bacterial
      peritonitis, and those at greatest risk should receive antibiotic prophylaxis.
      When spontaneous bacterial peritonitis is suspected, prompt diagnostic
      paracentesis followed by broad-spectrum antibiotics and albumin infusion can be
      life saving. Orthotopic liver transplantation should be considered in all
      patients with decompensated liver disease with or without ascites.

PMID- 15580153
TI  - Clostridium difficile-associated diarrhea: risk factors, diagnostic methods, and
      treatment.
AB  - Clostridium difficile-associated diarrhea (CDAD) has become the most common cause
      of infectious diarrhea acquired in the hospital, with an estimated 3 million
      annual cases and an annual cost of $1 billion. Risk factors for CDAD include
      antibiotic use (especially ampicillin, clindamycin, and cephalosporins), advanced
      age, and gastrointestinal surgery. Specific diagnosis of CDAD is made with an
      enzyme immunoassay to detect toxins A and B. Metronidazole remains the initial
      treatment of choice, with a 95% success rate. Vancomycin is reserved for
      failures. Despite the high initial success rates, recurrence of CDAD remains a
      significant problem in 20% to 30% of cases, with increased cost and substantial
      morbidity. Efforts to prevent CDAD will need to be strengthened, including
      education and better compliance with isolation, use of gloves, and hand washing.

PMID- 15580154
TI  - Adalimumab: human recombinant immunoglobulin g1 anti-tumor necrosis factor
      monoclonal antibody.
AB  - Tumor necrosis factor (TNF) is a proinflammatory cytokine that is involved with
      normal inflammatory and immune responses and with the pathogenesis of chronic
      inflammatory medical conditions, such as rheumatoid arthritis, psoriatic
      arthritis, plaque psoriasis, and Crohn's disease. The newest therapies for these
      inflammatory conditions include the TNF biologic response modifiers infliximab,
      etanercept, and adalimumab. Adalimumab is a human recombinant immunoglobulin G1
      anti-TNF monoclonal antibody. As monotherapy, or in combination with methotrexate
      or other traditional disease-modifying antirheumatic drugs, adalimumab can
      produce improvements in the signs and symptoms associated with rheumatoid
      arthritis and can slow progression of the joint destruction. The adverse effect
      profile of adalimumab seems to be comparable to that of etanercept. Adalimumab
      also seems to be useful in the treatment of psoriasis, psoriatic arthritis, and
      Crohn's disease; however, none of these indications are approved by the US Food
      and Drug Administration, and the optimal dosing regimen for these indications has
      not been established.

PMID- 15580155
TI  - True culprit or guilt by association? Is sphincter of Oddi manometry the cause of
      post-ERCP pancreatitis in patients with suspected sphincter of Oddi dysfunction,
      or is it the patients' susceptibility?

PMID- 15580156
TI  - New guidelines for treatment of complicated intra-abdominal infections.

PMID- 15580157
TI  - The relationship of cigarette smoking to peripheral arterial disease.
AB  - Cigarette smoking is one of the most important risk factors for peripheral
      arterial disease (PAD). Smoking increases the risk of PAD by several fold and is
      a more influential risk factor for PAD than for coronary artery disease. Multiple
      pathophysiologic mechanisms may account for the prevalence of atherosclerosis in
      cigarette smokers. These include abnormalities of endothelial function,
      lipoprotein metabolism, coagulation, and platelet function. Smoking cessation
      decreases the risk of cardiovascular morbidity and mortality, and may improve
      functional capacity in patients with PAD. Therapies to promote smoking cessation
      include counseling, nicotine replacement, and bupropion. Healthcare providers
      must enhance their efforts and target smoking cessation as a modifiable risk
      factor in patients with PAD and other manifestations of atherosclerosis.

PMID- 15580158
TI  - Immunotherapy for atherosclerosis: an emerging paradigm.
AB  - Experimental and clinical studies have implicated the immune system in
      atherogenesis and its complications. Recent studies have identified a complex
      dual role for the immune system: some aspects of the system play a proatherogenic
      role, whereas other aspects are atheroprotective. Suppression of proatherogenic
      immune responses and activation of antiatherogenic immune responses promise to
      emerge as novel strategies for the prevention and treatment of atherosclerotic
      vascular disease.

PMID- 15580159
TI  - Current advances in the diagnosis and treatment of renal artery stenosis.
AB  - Renal artery stenosis (RAS) is a common condition associated with hypertension
      and renal insufficiency. The high prevalence of RAS patients with coronary and
      lower extremity vascular disease has been well established. Fibromuscular
      dysplasia in young females and atherosclerosis in patients over the age of 55 are
      the most common causes. Poorly controlled hypertension refractory to medical
      therapy, worsening of renal function, and flash pulmonary edema may point to
      underlying RAS. Duplex ultrasonography and magnetic resonance angiography have
      largely replaced captopril scanning for RAS screening. However, renal angiography
      still remains the gold standard to diagnose RAS. Treatment options include
      medical therapy, angioplasty, and surgery. In general, patients with a stenosis
      greater than 50%, a translesional systolic pressure gradient greater than 15 mm
      Hg, and difficult-to-control hypertension and/or worsening renal insufficiency
      are candidates for renal revascularization. Percutaneous transluminal
      revascularization has evolved to become the preferred revascularization therapy
      because it is a less invasive and more cost-effective alternative to surgery and
      is associated with high technical success, as well as a low complication rate.
      The natural history of RAS is to progress over time, leading to renal artery
      occlusion, loss of renal mass, worsening of renal function, and, ultimately, end
      stage renal disease. It is therefore important to aggressively screen, recognize,
      and treat the entity early in its course.

PMID- 15580162
TI  - Pheochromocytoma storm presenting as cardiovascular collapse at term pregnancy.
AB  - Pheochromocytomas are neuroendocrine tumors that typically present with paroxysms
      of hypertension, but occasionally can lead to marked hemodynamic instability,
      left ventricular dysfunction, and cardiovascular collapse. Although
      pheochromocytoma in pregnancy is rare, factors specific to pregnancy can
      precipitate catecholamine crisis, making diagnosis and treatment challenging. We
      present a case of acute cardiovascular collapse with transient left ventricular
      dysfunction due to catecholamine crisis in a healthy young woman at term
      pregnancy. Further clinical and genetic investigation revealed pheochromocytoma
      as part of multiple endocrine neoplasia IIa (Sipple syndrome). A discussion of
      diagnosis and treatment strategies for pheochromocytoma in pregnancy and acute
      catecholamine crisis accompanies this report.

PMID- 15580165
TI  - Reticuline exposure to invertebrate ganglia increases endogenous morphine levels.
AB  - OBJECTIVES: Given the presence of morphine, its metabolites and precursors in
      mammalian and invertebrate tissues, it became important to determine if exposing
      tissues to an opiate alkaloid precursor, reticuline, would result in increasing
      endogenous morphine levels. METHOD: Endogenous morphine levels were determined by
      high pressure liquid chromatography coupled to electrochemical detection and
      radioimmunoassay following incubation of Mytilus edulis pedal ganglia with
      reticuline. Nitric oxide (NO) release was determined in real-time via an
      amperometric probe. Mu opiate receptor affinity for opiate alkaloid precursors
      was determined by a receptor displacement assay. RESULTS: Morphine is present in
      the pedal ganglia of Mytilus edulis (1.43 +/- 0.41 ng/mg +/- SEM ganglionic wet
      weight). Ganglia incubated with 50 ng of reticuline, a morphine precursor in
      plants, for 1 hour exhibited a statistical increase in their endogenous morphine
      levels (6.7 +/- 0.7 ng/mg tissue wet weight; P<0.01). This phenomenon is
      concentration dependent. The increase in ganglionic morphine levels occurs
      gradually over the 60 min incubation period, beginning 10 minutes post reticuline
      addition. We show that reticuline (10(-6) M) does not stimulate ganglionic NO
      release in a manner resembling that of morphine (10(-6) M), which releases NO
      seconds after its exposure to the ganglia and lasts for 5 minutes. With
      reticuline, there is a 3 minute delay, which is followed by an extended release
      period. Furthermore, in binding displacement experiments both reticuline and
      salutaridine (another morphine precursor) exhibit no binding affinity for the
      pedal ganglia mu opiate receptor subtype. This finding is further substantiated
      using the positive control of human monocytes where the mu3 opiate receptor
      subtype has been cloned. CONCLUSION: Taken together, we surmise that the
      morphine's precursors are being converted to morphine. The experiments strongly
      indicate that pedal ganglia can synthesize morphine from reticuline.

PMID- 15580166
TI  - Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a
      moderator.
AB  - The etiology of most cases of Alzheimer's disease (AD) is as yet unknown.
      Epidemiological studies suggest that environmental factors may be involved beside
      genetic risk factors. Some studies have shown higher mercury concentrations in
      brains of deceased and in blood of living patients with Alzheimer's disease.
      Experimental studies have found that even smallest amounts of mercury but no
      other metals in low concentrations were able to cause all nerve cell changes,
      which are typical for Alzheimer's disease. The most important genetic risk factor
      for sporadic Alzheimer's disease is the presence of the apolipoprotein Ee4 allele
      whereas the apolipoprotein Ee2 allele reduces the risk of developing Alzheimer's
      disease. Some investigators have suggested that apolipoprotein Ee4 has a reduced
      ability to bind metals like mercury and therefore explain the higher risk for
      Alzheimer's disease. Therapeutic approaches embrace pharmaceuticals which bind
      metals in the brain of patients with Alzheimer's disease. In sum, both the
      findings from epidemiological and demographical studies, the frequency of amalgam
      application in industrialized countries, clinical studies, experimental studies
      and the dental state of AD patients in comparison to controls suggest a decisive
      role for inorganic mercury in the etiology of AD.

PMID- 15580167
TI  - The change of regional brain metabolism (18FDG PET) in panic disorder during the
      treatment with cognitive behavioral therapy or antidepressants.
AB  - BACKGROUND: The goal of our study was to identify brain structures in patients
      with panic disorder (PD) that show changes in 18FDG PET during the treatment with
      cognitive behavioral therapy (CBT) or antidepressants. METHOD: Twelve patients
      suffering from panic disorder were studied with [18F]-2-fluoro-deoxyglucose
      positron emission tomography (18FDG PET) scanning during resting state (condition
      of random episodic silent thinking, REST). After PET examination patients were
      randomly assigned to either cognitive behavioral treatment group (6 patients) or
      antidepressants treatment group (6 patients). After a 3 month period 18FDG PET
      examination was repeated in both groups. Psychopathology was assessed using the
      rating scales HAMA, CGI and Panic Disorder Severity Scale (PDSS). Data were
      analysed using software for statistical parametric mapping (SPM99). RESULTS: The
      scores of psychopathology rating scales (CGI, HAMA, PDSS) decreased in both
      groups. Changes of 18FDG uptake in the pharmacotherapy group: decreases were
      found in the a priori hypothesized regions in the right hemisphere, in the
      superior, middle, medial and inferior frontal gyrus, superior and middle temporal
      gyrus, and increases were detected in the a priori hypothesized regions, mainly
      in the left hemisphere in medial and middle frontal gyrus, superior, middle and
      transverse temporal gyrus. Changes of 18FDG uptake in the CBT group: decreases
      were found in the a priori hypothesized regions of the right hemisphere in the
      inferior temporal gyrus, superior and inferior frontal gyrus, and increases were
      detected in the a priori hypothesized region, mostly in the left hemisphere:
      inferior frontal gyrus, middle temporal gyrus and insula. We did not detect
      changes in 18FDG uptake in the limbic region (hippocampus, parahippocampal gyrus
      and amygdala). CONCLUSIONS: Changes in brain metabolism (18FDG uptake) after the
      treatment either with CBT or with antidepressants were similar in number of brain
      areas, with prominent right-left difference. This is in concordance with the
      asymmetry of brain activity noted in patients with PD according to previous PET
      (and SPECT) studies.

PMID- 15580169
TI  - Effects of long-term use Topiramate on fertility and growth parameter in adult
      male rats.
AB  - PURPOSE: A case control study was conducted to assess the effects of long-term
      ingestion of Topiramate on fertility, body and reproductive organ weight and
      level of sex hormones in Sprague-Dawley male rats. METHODS: Ten adult male rats
      were exposed to Topiramate diets at a concentration of 100 mg /kg for 60 days.
      Another ten control male rats received vehicle (distilled water). After 24 hours
      of the last dose, animals were autopsied under light anesthesia. Several
      parameters including, body and reproductive organ weight, sperm count and
      motility, serum testosterone, FSH, levels of cholesterol, triglyceride, SGOT and
      SGPT were all measured. Assessment of pregnancies in females mixed with tested
      males was also measured. The results of histological, histometrical and
      biochemical profiles were compared to that of the control group, and the
      significance of these results was measured using student's ''t'' and Chi- square
      tests. RESULTS: Long-term ingestion of Topiramate for 60 days caused a
      significant decrease in spermatogenesis in seminiferous tubules of the testes.
      Sperm motility and density were also significantly reduced in cauda epididymides
      and testes of the treated group. The body weights and weight of reproductive
      organs (testes, epididymides, ventral prostate and seminal vesicle) were
      decreased considerably. Hormonal assay also showed significant decrease in
      testosterone levels. Testicular cell population dynamics also demonstrated a
      decrease in the number of both primary and secondary spermatocytes and spermatids
      in the treatment group. The number of female rats impregnated by male rats on
      long-term Topiramate diet had decreased. The number of implantations and the
      number of viable fetuses were also notably decreased in female rats impregnated
      by male rats ingested Topiramate. Histometry of reproductive organs confirmed
      these results. CONCLUSION: these results confirm that the long-term Topiramate
      ingestion produces adverse effects on fertility and reproductive system in adult
      male rat.

PMID- 15580170
TI  - Serum levels of growth factors HGF (Hepatocyte Growth Factor), TGFbeta1
      (transforming growth factor beta1) and IGF-I (Insulin Like Growth Factor I) in
      parathyroid tumors.
AB  - INTRODUCTION: HGF (Hepatocyte Growth Factor), TGFbeta1 (Transforming Growth
      Factor beta1) and IGF-I (Insulin Like Growth Factor I) are cytokines that are
      involved in the parathyroid tumors formation and growth. We tried to determine,
      if there are changes and relationships in the production of these cytokines by
      tumor cells of parathyroid tumors. MATERIAL AND METHODS: We determined
      concentrations of HGF, TGFbeta1 and IGF-I in serum from peripheral blood of 16
      patients with parathyroid adenoma and of 8 patients with parathyroid secondary
      hyperplasia before and after parathyroidectomy. Results were compared with serum
      levels in healthy people. RESULTS: Both preoperative and postoperative HGF serum
      levels in patients with parathyroid adenoma and secondary hyperplasia are
      significantly higher than in healthy people. Preoperative and postoperative serum
      levels of TGFbeta1 in parathyroid adenoma and postoperative TGFb1 serum levels in
      parathyroid secondary hyperplasia are higher, compared with those in the healthy
      population and in parathyroid secondary hyperplasia preoperatively. There are no
      significant differences of IGF-I serum levels among the all investigated groups
      of patients. CONCLUSIONS: Changes in the growth factors production by parathyroid
      tumor cells are reflected by their concentrations in peripheral blood. The
      elevation of HGF serum levels in patients with parathyroid adenoma and
      hyperplasia can be explained by very high HGF production by tumor cells.
      Nevertheless, there is no decrease of HGF serum levels after the
      parathyroidectomy. That may be the result of the extratumoral production of this
      cytokine. Also TGFbeta1 and IGF-I serum levels indicate high possibility of the
      extratumoral production of these cytokines. Higher postoperative IGF-I serum
      levels (but not significantly) in parathyroid secondary hyperplasia are in
      accordance with its bone production.

PMID- 15580171
TI  - Intermittent hypoxia causes a suppressed pituitary growth hormone through
      somatostatin.
AB  - OBJECTIVES: The aim of this study was to investigate the response of the growth
      hormone (GH) in rat anterior pituitary to intermittent hypoxia (IH) and its
      modulation by hypothalamic somatostatin (SS). SETTING AND DESIGN: To observe the
      hypoxic response, rats were exposed to simulated altitude hypoxia (2 km or 5 km)
      in a hypobaric chamber for various days (4 h/d); to clarify SS-involvement, rats
      were pretreated with SS antagonist (cysteamine, CSH, 200 mg/kg/d, s.c.) then
      exposed to IH (5 km) for 2d. The GH mRNA and immunostaining GH in pituitary as
      well as immunostaining SS in median eminence (ME) of hypothalamus were assayed by
      RT-PCR and immuno-histochemistry, respectively. RESULTS: IH of 5 km altitude
      (IH5) markedly suppressed the body weight gain (BWG) of rats from 1d to 10d, and
      it was returned to control level henceforth, while no significant influence was
      showed in the group of IH of 2 km altitude (IH2). IH5 for 2 and 5d significantly
      decreased GH mRNA expression in the pituitary. The pituitary immunostaining GH
      was remarkably increased in groups of IH2 for 5, 10, and 15 d, and in groups of
      IH5 for 2, 5, and 10d. Immunostaining SS in ME was significantly reduced in group
      of IH2 for 5d, and in groups of IH5 for 2d and 5d. Pretreatments (s.c.) with SS
      antagonist (CSH) significantly reversed IH5-caused increase of immunostaining GH
      and reduction of mRNA levels in pituitary. CONCLUSIONS: IH may cause a short-term
      and recoverable suppression of GH release, and reduce GH mRNA expression in
      anterior pituitary, which may depend on the intensity and duration of the
      hypoxia. This suppression may be due to a modulation of hypoxia-activated SS.

PMID- 15580172
TI  - The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible
      interactions in the control of body temperature.
AB  - OBJECTIVE: Melatonin plays a role in the regulation of biological rhythms, body
      temperature presents circadian variations with lower levels during nighttime,
      when melatonin levels are very high, and thyroid hormones influence shiver
      independent thermogenesis. We have investigated on possible interactions between
      the hypothalamic-pituitary-thyroid axis and melatonin in the control of body
      temperature in humans. METHODS: Peripheral blood samples for thyrotropin
      releasing hormone (TRH), thyroid-stimulating hormone (TSH), free-thyroxine (FT4),
      melatonin levels determination and body temperature measurements were obtained
      every four hours for 24-hours starting at 0600 h in a controlled temperature and
      light-dark environment from ten healthy males, aged 38-65 (mean age +/-s.e.
      57.4+/-3.03, mean body mass index +/-s.e. 25.5+/-0.75). We calculated fractional
      variation and correlation on single time point hormone serum levels and tested
      whether the time-qualified data series showed consistent pattern of circadian
      variation. RESULTS: A statistically significant difference was evidenced for the
      fractional variation of daytime TSH serum levels (0600 h-1000 h vs. 1000 h-1400
      h, p=0.01, 1000 h-1400 h vs. 1400 h-1800 h, p=0.0001, 1400 h-1800 h vs. 1800 h
      2200 h, p=0.001) and for the fractional variation of FT4 serum levels at 1800 h
      2200 h vs. 2200 h-0200 h (p=0.02). FT4 serum levels correlated positively with
      TRH serum levels at 1000 h (r=0.67, P=0.03) and at 1400 h (r=0.63, p=0.04),
      negatively with TSH serum levels at 2200 h (r=-0.67, p=0.03), negatively with
      melatonin serum levels at 2200 h (r=-0.64, p=0.04) and at 0200 h (r=-0.73,
      p=0.01). TRH serum levels correlated positively with TSH serum levels at 0200 h
      (r=0.65, p=0.04) and at 0600 h (r=0.64, p=0.04). Body temperature correlated
      positively with FT4 serum levels at 1000 h (r=0.63, p=0.04) and negatively with
      melatonin serum levels at 0200 h (r=-0.64, p=0.04). A clear circadian rhythm was
      validated for body temperature (with acrophase in the morning) and melatonin, TRH
      and TSH secretion (with acrophase at night), while FT4 serum level changes
      presented ultradian periodicity (with acrophase in the morning). CONCLUSION:
      Changes of TSH serum levels are smaller and those of FT4 are greater at night,
      when melatonin levels are higher, so that the response of anterior pituitary to
      hypothalamic TRH and of thyroid to hypophyseal TSH may be influenced by the
      pineal hormone that may modulate the hypothalamic-pituitary-thyroid axis function
      and influence the circadian rhythm of body temperature.

PMID- 15580173
TI  - The influence of antibiotic treatment on tocolysis in threatened advanced
      pregnancy.
AB  - OBJECTIVE: The aim of this study was to determine: a) to what extent application
      of antibiotics enhances efficiency of tocolysis; b) whether the duration of
      antibiotic treatment influences its efficacy; c) what criterion is decisive for
      efficacy of tocolysis assisted by antibiotic therapy. MATERIALS AND METHODS: 223
      successive women with unifetal pregnancies, aged 17 to 42 (average age 27.3),
      admitted to the Department of Gynecology and Obstetrics of the JU Medical College
      in the period from January 1, 1999 to September 9, 2001, were enrolled in the
      study. Using clinical methods such as: assessment of contractile activity of the
      uterus, of uterine cervix and membranes, presence of bleeding and other clinical
      symptoms, these women were diagnosed with imminent preterm labour. CONCLUSIONS:
      Antibiotic treatment enhances the efficacy of tocolysis, influencing the time of
      prolonging pregnancy in imminent preterm delivery. This synergistic effect is
      clinically crucial as in this way significantly larger number of children will be
      born at term and also a number of premature neonates who survive may be
      increased.

PMID- 15580174
TI  - Investigation of the influence of training status on the relationship between the
      acute exercise and serum leptin levels in obese females.
AB  - OBJECTIVE: Recent studies have concluded that an energy expenditure by an acute
      exercise session has no immediate effect on leptin levels while some showed a
      decline in leptin levels. The purpose of this study was to investigate any
      possible effects of training status of the subjects on acute exercise-leptin
      relationship in obese patients. MATERIALS AND METHODS: Fourteen obese sedentary
      females were enrolled to the study and effects of acute incremental exercise on
      serum leptin levels were determined at rest and at maximal exercise performance.
      Then, they participated to a 12-weeks endurance aerobic training programme
      performed in the laboratory on a computer controlled cycle ergometer and their
      leptin levels were re-evaluated and the leptin-acute exercise relationships
      obtained under different training levels in the same group of subjects were
      compared. The body compositions were determined by bioelectrical impedance. Pre
      and post training blood samples were taken at rest and at the maximal exercise
      performance. Serum leptin levels were analysed in duplicate by RIA. Data were
      evaluated using, paired t and Pearson's tests. RESULTS: Leptin levels were not
      acutely affected by the incremental exercise either before (23.62+/-3.5 ng/ml and
      22.62+/-3.6 ng/ml) or after (13.13+/-3.4 ng/ml and 13.82+/-3.6 ng/ml) endurance
      training. The marked decrease in leptin levels following training was closely
      correlated with fat mass loss R= 0.899 (P= 0.0001). CONCLUSIONS: This study
      indicates that an increase in energy expenditure by acute exercise has no
      significant acute effect on leptin level regardless of the training status of the
      subjects and decrease in leptin levels after a 12-weeks endurance aerobic
      training programme are closely associated with the fat mass loss.

PMID- 15580175
TI  - Salivary cortisol in panic: are males more vulnerable?
AB  - OBJECTIVES: The underlying mechanisms of panic attacks (PA's) are still unclear.
      Theories focusing on these mechanisms differ in their description of the
      relationship between panic and fear. The main controversy concerns whether a PA
      resembles the classical flight response, or whether it is qualitatively different
      from fear. According to the first theory, a PA would result in hypothalamic
      pituitary-adrenal axis (HPA-axis) activation, whereas according to the second, it
      would not. So far, inconclusive results have been reported in studies measuring
      HPA-axis activity after laboratory evoked PA's. The present study was designed to
      assess cortisol levels following a 35% CO2 challenge in Panic Disorder (PD)
      patients compared to healthy volunteers as a measurement of HPA-axis activity.
      DESIGN: Twenty-three PD patients and 20 healthy volunteers participated in the
      study. Cortisol was determined in saliva at regular intervals before and after
      the challenge. Furthermore, attention was paid to possible gender effects.
      RESULTS: Although the 35% CO2 inhalation induced a significant increase in
      anxiety, no cortisol increase was found. Moreover, there was no difference
      between patient and control cortisol values following the 35% CO2 challenge,
      whereas the delta anxiety scores were far more pronounced in the patient group.
      Interestingly, male PD patients showed higher cortisol values. CONCLUSIONS: This
      study may be in accordance with the view that PA's are not accompanied by an
      important HPA-axis activation. There are some indications for aberrant cortisol
      secretion in male PD patients. Further research needs to confirm whether male and
      female PD patients differ in their underlying mechanisms related to HPA-axis
      activity.

PMID- 15580176
TI  - Psychological, neuroendocrine and immune measures in non spousal carers of
      disabled elderly in Italy.
AB  - OBJECTIVES: The purpose of this study was to determine whether psychological well
      being as well as metabolic, neuroendocrine and immune functions were different in
      non spousal primary caregivers of disabled elderly than in controls. SETTING AND
      DESIGN: We randomly recruited 38 primary family carers of over 65 year old
      recipients of health home care services and 37 controls stratified according to
      sex and age. METHOD: Data were collected on psychological wellbeing (including
      anxiety, depression and self-perceived quality of life), on neuroendocrine and
      immune conditions (haemanalysis and metabolic signs, plasma ACTH, cortisol,
      prolactin, intra-lymphocyte content of beta-endorphins, NK cell activity and
      number), as well as on the incidence and severity of influenza disease during
      previous winter. RESULTS: Caregivers showed greater anxiety, although mean scores
      did not reach pathological levels. Neither depression nor satisfaction on quality
      of life did differ significantly, nor differences in haemanalisis and metabolic
      signs were found, apart from leukocyte and lymphocyte number, which was
      significantly lower in carers. Plasma levels of ACTH, cortisol and prolactin, the
      intra-lymphocyte content of beta-endorphins as well as the NK cell number and
      cytotoxicity did not show significant differences. Incidence and severity of
      influenza episodes was also similar, whereas the duration of influenza disease
      showed to be significantly longer. CONCLUSIONS: Non spousal caregivers of
      disabled elderly suffer from only slight alterations of psychological, endocrine
      and immune parameters, and do not respond very differently to influenza disease.
      This does not support therefore any generic privilege for them in the allocation
      of public support or respite services.

PMID- 15580187
TI  - Sleep deprivation, residency training, and ACGME rules: practical guidelines.

PMID- 15580188
TI  - One small step for man...?

PMID- 15580189
TI  - To avoid heat loss in very preterm infants.

PMID- 15580190
TI  - Brain protection for girls and boys.

PMID- 15580191
TI  - Chronic orthostatic intolerance and the postural tachycardia syndrome (POTS).

PMID- 15580192
TI  - Inflammation, insulin, and endothelial function in overweight children and
      adolescents: the role of exercise.
AB  - OBJECTIVES: To assess subclinical inflammation, fasting insulin, and endothelial
      function before and after exercise in overweight children and adolescents. STUDY
      DESIGN: Twenty-five children (body mass index [BMI] >85th percentile) were
      assessed for brachial artery flow-mediated dilation (FMD), nitroglycerin-induced
      dilation, C-reactive protein (CRP), lipids, glucose, insulin, oral glucose
      tolerance, body composition, aerobic fitness (peak oxygen uptake [VO 2 peak]),
      and blood pressure. Twenty of these persons were equally and randomly assigned to
      either 8 weeks of stationary cycling or to a non-exercising control group.
      RESULTS: A baseline correlation was found between CRP and fasting insulin (r =
      0.62; P < .001), which remained significant after adjusting for baseline
      variables (r = 0.53; P < .05). After 8 weeks, significant improvements were
      observed in the exercise group compared with the control group for VO 2 peak
      (exercise group = 21.8 +/- 2.1 to 23.2 +/- 1.5 mL/kg/minute vs control group =
      23.4 +/- 1.6 to 20.9 +/- 2.2 mL/kg/minute; P < .05), high-density lipoprotein
      (HDL) cholesterol (exercise group = 1.02 +/- 0.03 to 1.10 +/- 0.04 mmol/L vs
      control group = 1.08 +/- 0.07 to 0.99 +/- 0.09 mmol/L; P < .05), and FMD area
      under the curve (AUC) (exercise group = 746 +/- 66 to 919 +/- 94 %*sec vs control
      group = 731 +/- 102 to 515 +/- 73 %*sec; P < .05). CONCLUSIONS: In overweight
      children and adolescents, CRP is independently associated with fasting insulin.
      Eight weeks of aerobic exercise improves fitness, HDL cholesterol, and
      endothelial function in this group.

PMID- 15580193
TI  - Relations of fatness and fitness to fasting insulin in black and white
      adolescents.
AB  - OBJECTIVE: To determine in black and white youths the degree to which fatness and
      cardiovascular fitness (CVF) explained independent proportions of the variance in
      fasting insulin concentrations. STUDY DESIGN: Youths 14 to 18 years of age (n =
      278) were studied. Insulin was measured after a 12-hour fast. Percent body fat
      (%BF) was measured with dual-energy x-ray absorptiometry. CVF was determined with
      a multistage treadmill test. RESULTS: Girls had higher %BF and lower CVF than
      boys. Whites were higher in CVF than blacks. There was a race by sex interaction
      for fasting insulin concentration, such that black girls had the highest and
      white girls had the lowest concentrations. When %BF and CVF was controlled
      statistically, this interaction was no longer significant. Multiple regression
      models that controlled for race, sex, and their interaction showed that (1) both
      higher %BF and lower CVF were significantly associated with higher insulin
      concentrations; (2) there were significant interactions with sex, such that the
      deleterious effects of low CVF and high %BF were greater in boys than in girls;
      (3) there was a significant CVF-%BF interaction, such that youths who were both
      fit and lean had especially low insulin concentrations; and (4) sex-specific
      regressions showed that both %BF and CVF explained significant independent
      proportion of the insulin variance for the boys but that only %BF did so for the
      girls. CONCLUSIONS: Interventions to prevent hyperinsulinemia in youths should be
      designed both to minimize fatness and maximize CVF.

PMID- 15580194
TI  - Growth hormone improves mobility and body composition in infants and toddlers
      with Prader-Willi syndrome.
AB  - OBJECTIVES: To determine the effect of growth hormone (GH) on body composition
      and motor development in infants and toddlers with Prader-Willi syndrome (PWS).
      STUDY DESIGN: Twenty-nine subjects with PWS (4-37 months of age) were randomized
      to GH treatment (1mg/m 2 /day) or observation for 12 months. Percent body fat,
      lean body mass, and bone mineral density were measured by dual x-ray
      absorptiometry; energy expenditure was measured by deuterium dilution; and motor
      constructs of mobility (M) and stability (S) were assessed using the Toddler
      Infant Motor Evaluation (TIME). RESULTS: GH-treated subjects, compared with
      controls, demonstrated decreased percent body fat (mean, 22.6% +/- 8.9% vs 28.5%
      +/- 7.9%; P < .001), increased lean body mass (mean, 9.82 +/- 1.9 kg vs 6.3 +/-
      1.9 kg; P < .001), and increased height velocity Z scores (mean, 5. 0 +/- 1.8 vs
      1.4 +/- 1.0; P < .001). Patients who began GH before 18 months of age showed
      higher mobility skill acquisition compared with controls within the same age
      range (mean increase in raw score, 284 +/- 105 vs 206 +/- 63; P < .05).
      CONCLUSIONS: GH treatment of infants and toddlers with PWS for 12 months
      significantly improves body composition and when begun before 18 months of age
      increases mobility skill acquisition. These results suggest that GH therapy
      instituted early in life may lessen deterioration of body composition in PWS
      while also accelerating motor development.

PMID- 15580195
TI  - Heat Loss Prevention (HeLP) in the delivery room: A randomized controlled trial
      of polyethylene occlusive skin wrapping in very preterm infants.
AB  - OBJECTIVES: To determine if polyethylene occlusive skin wrapping of very preterm
      infants prevents heat loss after delivery better than conventional drying and to
      evaluate if any benefit is sustained after wrap removal. STUDY DESIGN: This was a
      randomized controlled trial of infants <28 weeks' gestation. The experimental
      group was wrapped from the neck down. Only the head was dried. Control infants
      were dried completely. Rectal temperatures were compared on admission to the
      neonatal intensive care unit immediately after wrap removal and 1 hour later.
      RESULTS: Of 55 infants randomly assigned (28 wrap, 27 control), 2 died in the
      delivery room and 53 completed the study. Wrapped infants had a higher mean
      rectal admission temperature, 36.5 degrees C (SD, 0.8 degrees C), compared with
      35.6 degrees C (SD, 1.3 degrees C) in control infants ( P = .002). One hour
      later, mean rectal temperatures were similar in both groups (36.6 degrees C, SD,
      0.7 degrees C vs 36.4 degrees C, SD, 0.9 degrees C, P = .4). Size at birth was an
      important determinant of heat loss: Mean rectal admission temperature increased
      by 0.21 degrees C (95% CI, 0.04 to 0.4) with each 100-g increase in birth weight.
      CONCLUSIONS: Polyethylene occlusive skin wrapping prevents rather than delays
      heat loss at delivery in very preterm infants.

PMID- 15580196
TI  - Richardson score predicts short-term adverse respiratory outcomes in newborns
      >/=34 weeks gestation.
AB  - OBJECTIVES: To develop a model to predict which newborns >/=34 weeks gestation
      with respiratory distress will die or will require prolonged (>3 days) assisted
      ventilation. METHODS: Retrospective cohort study using data from Northern
      California newborns >/=34 weeks gestation who presented with respiratory
      distress. We split the cohort into derivation and validation datasets. Bivariate
      and multivariate data analyses were performed on the derivation dataset. After
      developing a simple score on the derivation dataset, we applied it to the
      original as well as to a second validation dataset from Massachusetts. RESULTS:
      Of 2276 babies who met our initial eligibility criteria, 203 (9.3%) had the
      primary study outcome (assisted ventilation >3 days or death). A simple score
      based on gestational age, the lowest PaO 2 /FIO 2 , a variable combining lowest
      pH and highest PaCO 2 , and the lowest mean arterial blood pressure had excellent
      performance, with a c-statistic of 0.85 in the derivation dataset, 0.80 in the
      validation dataset, and 0.80 in the secondary validation dataset. CONCLUSIONS: A
      simple objective score based on routinely collected physiologic predictors can
      predict respiratory outcomes in infants >/=34 weeks gestation with respiratory
      distress.

PMID- 15580197
TI  - Rapid advancement to more concentrated formula in infants after surgery for
      congenital heart disease reduces duration of hospital stay: a randomized clinical
      trial.
AB  - OBJECTIVE: To determine the impact of rapid advancement to more concentrated
      formula on weight gain and duration of hospitalization for infants after cardiac
      surgery. STUDY DESIGN: We performed a double-blinded, randomized trial of rapid
      advancement to higher achieved formula concentration for postoperative infants
      younger than 1 year of age. After transfer to the inpatient ward from the
      critical care unit, infants were randomly assigned to rapid advancement to a
      higher achieved formula concentration (2-day transition) or usual care (5-day
      transition, lower concentration target). RESULTS: The adequacy of energy intake
      (expressed as the median percentage of the estimated energy requirement) before
      discharge from the hospital was 98% in the intervention versus 78% in the usual
      care group ( P = .01). Before discharge, the median rate of weight gain was
      greater in the rapid advancement (20 g/d) versus the usual care group (loss of 35
      g/d, P < .03). The median postoperative duration of stay on the cardiology
      inpatient unit was 5 days for the intervention versus 6 days for the usual care
      group ( P < .05). CONCLUSIONS: Rapid advancement to higher achieved formula
      concentration significantly improved energy intake and weight gain and decreased
      duration of postoperative hospital stay in infants after cardiac surgery.

PMID- 15580198
TI  - Follow-up care of children identified with ADHD by primary care clinicians: A
      prospective cohort study.
AB  - OBJECTIVE: To document follow-up care received by children identified with
      attention deficit hyperactivity disorder (ADHD) by primary care clinicians
      (PCCs). STUDY DESIGN: We surveyed families of children 4 to 15 years of age who
      had been diagnosed with ADHD. At an index office visit, parents and clinicians
      completed questionnaires. Six months after the index visit, parents completed a
      questionnaire (N = 659 returned surveys, 68% return rate). The main outcome
      measure was the number of visits with the patients' PCCs or mental health
      specialists during the 6 months after the index visit. RESULTS: Children had a
      median of one visit PCC over a period of 6 months. Children who had prescriptions
      for psychotropic medications (78%) did not differ from others in the number of
      visits. Follow-up visits with the child's own doctor were more common when the
      PCC had completed mental health training. Only 26% of patients saw a mental
      health specialist. Children who were black, on Medicaid, or with higher levels of
      internalizing symptoms were more likely to see a mental health specialist.
      CONCLUSIONS: Children treated for ADHD need more follow-up visits to permit
      adjustment of medication and support continuation of patients in treatment.
      Systematic quality improvement efforts are warranted.

PMID- 15580199
TI  - Improving follow-up for children with asthma after an acute Emergency Department
      visit.
AB  - OBJECTIVE: To improve follow-up with primary care providers after acute Emergency
      Department (ED) asthma visits for children from low-income urban families. STUDY
      DESIGN: A prospective, randomized, controlled trial evaluated combined telephone
      asthma coaching and monetary incentive. The primary outcome was asthma-planning
      visits with primary care providers within 15 days of index ED visits. The
      subjects were urban parents whose children were treated for asthma in the ED and
      had Medicaid or no insurance. RESULTS: We enrolled 527 parents (264 control and
      263 intervention). There was a significant difference ( P < .0001) between the
      intervention (35.7%) and control (18.9%) groups in the proportion of children who
      had asthma-planning visits and decreased mean nights/days with asthma symptoms by
      4.36 intervention and 3.31 control at 2 weeks. The proportions of children with
      asthma-planning visits and acute asthma care visits during the 16-day to 6-month
      period were similar for both groups. CONCLUSIONS: Telephone coaching and a
      monetary incentive significantly increased the proportion of low-income urban
      parents who brought their children for asthma-planning visits, and decreased
      asthma symptoms shortly after asthma ED visits. The intervention did not increase
      subsequent asthma-planning visits or decrease ED visits or hospitalizations.

PMID- 15580200
TI  - Health-related quality of life and psychosocial adjustment in steroid-sensitive
      nephrotic syndrome.
AB  - OBJECTIVES: To evaluate quality of life (QOL) and psychosocial adjustment by
      standardized tests in well-characterized patients with steroid-sensitive
      nephrotic syndrome. STUDY DESIGN: Forty-five patients were investigated at a
      median age of 9.8 years (range, 3.4 to 19.8) and 5.9 years (range, 0.1 to 16.3)
      since diagnosis. Child- and parent-rated QOL was evaluated by the The Netherlands
      Organization for Applied Scientific Research Academical Medical Center (TNO-AZL)
      Child Quality of life Questionnaire. Psychosocial adjustment was assessed by the
      Child Behavior Checklist and the Teacher Report Form. RESULTS: In patients, only
      the QOL subscale "social functioning" was impaired compared with that in control
      subjects, whereas parents rated 4 of a total of 7 subscales as abnormal.
      Psychosocial adjustment was impaired at home and at school. Steroid dependency
      and cytotoxic treatment had a significant negative impact on QOL only, whereas
      family climate, especially maternal distress, negatively affected both QOL and
      psychosocial adjustment. CONCLUSIONS: QOL and psychosocial adjustment are
      impaired in steroid-sensitive nephrotic syndrome. Both illness-related variables
      and family climate play an important role.

PMID- 15580202
TI  - Social-psychological correlates of peer victimization in children with endocrine
      disorders.
AB  - OBJECTIVE: To examine the relation between victimization by peers and child and
      parent reports of social-psychological adjustment. STUDY DESIGN: The Social
      Experience Questionnaire, Children's Depression Inventory, Social Anxiety Scale
      for Children-Revised, and Asher Loneliness Scale were administered to 93 children
      diagnosed with various endocrine disorders. The child's parent/guardian completed
      the Child Behavior Checklist. RESULTS: For the entire sample, peer victimization
      was positively related to child-reported depression, social anxiety, loneliness,
      and parent-reported externalizing symptoms. Those children with endocrine
      disorders without observable features had a stronger relation between peer
      victimization and depression and internalizing and externalizing behavior
      problems than did those who had endocrine disorders with observable physical
      features. CONCLUSIONS: Recognition of the magnitude of the problem and means of
      evaluating for peer victimization is important for clinicians who see children
      with chronic diseases.

PMID- 15580203
TI  - Anthropometry, metabolic control, and thyroid autoimmunity in type 1 diabetes
      with celiac disease: A multicenter survey.
AB  - OBJECTIVE: To investigate the influence of celiac disease (CD) on growth and
      metabolic control in a nationwide cohort of children and adolescents with type 1
      diabetes (T1D). STUDY DESIGN: We analyzed data from 19,796 pediatric patients
      with T1D in the German pediatric multicenter DPV-database for occurrence of CD.
      RESULTS: CD-specific antibodies were present in 1326 patients (6.7%). The
      diagnosis was confirmed in 127 patients (0.6%) by small-bowel biopsy. Female
      subjects were significantly more predisposed to have T1D and CD. The CD-affected
      patients in our cohort were significantly younger at diabetes onset. Furthermore,
      they had significantly lower height-SDS at onset (-0.49 vs -0.06, P < .05), a
      difference that increased during the course of the disease (-0.80 vs -0.26 after
      9 years of diabetes, P < .05). In addition, body mass index-SDS significantly
      differed between the groups (0.22 vs 0.47, P < .05). Evidence for thyroid disease
      was more commonly observed in the T1D with CD group (6.3% vs 2.3%, P < .05).
      HbA1c values were lower in the patients with T1D and CD. CONCLUSIONS: The CD
      positive patients were characterized by earlier onset of diabetes and decreased
      growth and weight gain. These findings emphasize the clinical relevance of celiac
      disease in patients with autoimmune diabetes.

PMID- 15580204
TI  - Epigenotyping as a tool for the prediction of tumor risk and tumor type in
      patients with Beckwith-Wiedemann syndrome (BWS).
AB  - OBJECTIVES: Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5%
      to 10% of developing childhood tumors, 60% of which are Wilms' tumors. Aberrant
      methylation of two distinct clusters of imprinted genes on chromosome 11p15 is
      detected in approximately 70% of BWS cases. Our aim was to determine associations
      between the imprinting status of both imprinting clusters (BWSIC1/2) and the
      tumor incidence and type. STUDY DESIGN: Methylation patterns of H19 and KCNQ1OT1
      were collected in 114 patients with BWS with a clinical diagnosis. The patients
      were followed until 5 years of age, and tumor incidence and type were registered.
      RESULTS: A lower risk of developing childhood tumors was found among patients
      with a methylation defect limited to BWSIC2 compared with other patients with
      BWS. No Wilms' tumors were found in this group, whereas in patients with a
      methylation defect limited to BWSIC1 Wilms' tumor was the most common tumor.
      CONCLUSIONS: In addition to clinical factors indicative for a high tumor risk
      (hemihypertrophy, nephromegaly), methylation patterns discriminate between
      patients with BWS with a high and low tumor risk. It also is possible to predict
      whether they are at risk of developing a Wilms' tumor. Epigenotyping of patients
      is important to select the type of screening protocol to be proposed to these
      patients.

PMID- 15580205
TI  - Recurrence of febrile seizures in the respiratory season is associated with
      influenza A.
AB  - OBJECTIVES: To investigate the association of viral infections and febrile
      seizures (FS). STUDY DESIGN: From April 1998 to April 2002, a prospective,
      population-based study was carried out among general practitioners to assess the
      incidence of FS in their practices. Data thus obtained were compared with the
      incidence of common viral infections recorded in a national registry. Poisson
      regression analysis was performed to investigate whether the season or the type
      of infection was associated with the variation observed in FS incidence. RESULTS:
      Throughout the 4-year period, 267 of 303 (88%) of general practitioners in the
      Dutch province of Friesland participated in the study. The estimated observation
      period was approximately 160,000 patient-years. We registered 654 cases of FS in
      429 children. The estimated incidence of FS was 2.4 in 1000 patient-years.
      Poisson regression analysis revealed a positive correlation between recurrent FS
      and influenza A ( P = .01). CONCLUSIONS: Our study suggests a relation between
      recurrent FS and influenza A. Influenza vaccination should be considered in all
      children with a history of FS.

PMID- 15580206
TI  - Hematopoietic stem cell transplantation for complete IFN-gamma receptor 1
      deficiency: a multi-institutional survey.
AB  - OBJECTIVES: To evaluate the outcome of hematopoietic stem cell transplantation
      (HSCT) in a series of patients with inherited complete IFN-gamma receptor 1
      (IFNgammaR1) deficiency. STUDY DESIGN: We report 8 patients who received
      altogether 11 HSCT from family donors, including 10 HLA-identical (5 siblings and
      5 relatives) and 1 HLA-haplo-identical donors. Five grafts were T-cell depleted,
      and conditioning regimens varied in intensity. RESULTS: Four patients died within
      8 months after HSCT. Two of these deaths were due to specific complications
      related to mycobacterial infection. There was no or very low (2%) donor cell
      engraftment in 2 survivors. Only 2 patients are in full remission of
      mycobacterial disease 5 years after HSCT. These are the only patients who
      received non-T-cell-depleted grafts from an HLA-identical sibling after a fully
      myeloablative conditioning regimen. CONCLUSIONS: HSCT can lead to prolonged
      remission of mycobacterial disease in children with complete IFNgammaR1
      deficiency. However, optimal control of mycobacterial infection before HSCT and
      the use of a non-T-cell-depleted transplant from an HLA-identical sibling after a
      fully myeloablative conditioning regimen are recommended.

PMID- 15580207
TI  - Cardiopulmonary fitness and muscle strength in patients with osteogenesis
      imperfecta type I.
AB  - OBJECTIVE: To evaluate cardiopulmonary function, muscle strength, and
      cardiopulmonary fitness (VO 2 peak) in patients with osteogenesis imperfecta
      (OI). STUDY DESIGN: In 17 patients with OI type I (mean age 13.3 +/- 3.9 years)
      cardiopulmonary function was assessed at rest using spirometry, plethysmography,
      electrocardiography, and echocardiography. Exercise capacity was measured using a
      maximal exercise test on a bicycle ergometer and an expired gas analysis system.
      Muscle strength in shoulder abductors, hip flexors, ankle dorsal flexor, and grip
      strength were measured. All results were compared with reference values. RESULTS:
      Cardiopulmonary function at rest was within normal ranges, but when it was
      compared with normal height for age and sex, vital capacities were reduced. Mean
      absolute and relative VO 2 peak were respectively -1.17 (+/- 0.67) and -1.41 (+/-
      1.52) standard deviations lower compared with reference values ( P < .01). Muscle
      strength also was significantly reduced in patients with OI, ranging from -1.24
      +/- 1.40 to -2.88 +/- 2.67 standard deviations lower compared with reference
      values. CONCLUSIONS: In patients with OI type I, no pulmonary or cardiac
      abnormalities at rest were found. The exercise tolerance and muscle strength were
      significantly reduced in patients with OI, which might account for their
      increased levels of fatigue during activities of daily living.

PMID- 15580208
TI  - Clinical and behavioral features of patients with Borjeson-Forssman-Lehmann
      syndrome with mutations in PHF6.
AB  - OBJECTIVE: To describe clinical and behavioral features of 10 men from 2 families
      with Borjeson-Forssman-Lehmann syndrome (BFLS) and missense mutations in the PHF6
      zinc-finger transcription factor gene. STUDY DESIGN: BFLS behavioral features
      were compared with other age-matched men with other syndromes and similar
      intellectual functioning through the use of standardized questionnaires: the
      Child Behavior Checklist, the Vineland Adaptive Behavior Scales, and the Reiss
      Personality Profile. Participants included 10 with BFLS, 10 with Prader-Willi
      syndrome, and 23 with Klinefelter syndrome variants (13 with 48,XXYY, 4 with
      48,XXXY, and 6 with 49,XXXXY). RESULTS: Contrary to initial reports, our men with
      BFLS had no microcephaly, seizures, or short stature. They manifested deep-set
      eyes with large ears, coarse facial features, small external genitalia,
      gynecomastia, and obesity. Family A had mild to moderate mental retardation,
      whereas family B was more severely affected. On Vineland Adaptive Behavior
      Scales, men with BFLS had higher daily living and social skills than
      communicative skills. Men with BFLS also had lower internalizing and
      externalizing symptoms and appeared more social and helpful than men with Prader
      Willi syndrome or Klinefelter syndrome variant. CONCLUSIONS: Men with BFLS from 2
      families with mutations in the PHF6 gene manifested distinctive clinical features
      and a low risk for maladaptive behaviors.

PMID- 15580209
TI  - Pulmonary arteriovenous malformations in children: outcomes of transcatheter
      embolotherapy.
AB  - OBJECTIVE: To describe outcomes of transcatheter embolotherapy (TCE) in children
      with pulmonary arteriovenous malformations (PAVMs). STUDY DESIGN: Chart and
      imaging review of all children (age </=18 years) treated for PAVMs by TCE at
      three hereditary hemorrhagic telangiectasia centers. RESULTS: All 42 treated
      patients were included, with a mean age of 12 years (range, 4 to 18). Cyanosis
      was present in 25 of 42 patients (60%). Hemoptysis had occurred in 3 of 42
      patients (7%) and neurologic complications (stroke, cerebral abscess) occurred in
      8 patients (19%) before assessment. PAVMs were focal in 30 of 42 (71%) and
      diffuse in 12 of 42 (29%) patients. TCE was performed for 172 PAVMs and 35
      diffuse regions (regional TCE). Follow-up was obtained in 38 of 42 (90%) patients
      (mean, 7 years). After TCE in patients with focal PAVMs, oxygenation improved
      significantly, with no further complications from the PAVMs. Reperfusion was
      noted in 23 of 153 (15%) PAVMs. Eighteen of 23 (78 %) of these were retreated,
      with documented aneurysmal involution in 10 of 13 (77%) patients. TCE
      complications included pleuritic chest pain (24% of sessions) and deployment
      complications (device paradoxical embolization or device misplacement) (3% of
      sessions, 1% of PAVMs), with no long-term complications. CONCLUSIONS: PAVMs cause
      life-threatening complications in children; treatment with TCE is safe, with
      complication rates comparable to adult rates.

PMID- 15580211
TI  - Prevention of intraventricular hemorrhage by indomethacin in male preterm
      infants.
AB  - Our multicenter Indomethacin Intraventricular Hemorrhage (IVH) Prevention Trial
      demonstrated a reduction of IVH in preterm infants. Analysis of our cohort by sex
      showed indomethacin halved the incidence of IVH, eliminated parenchymal
      hemorrhage, and was associated with higher verbal scores at 3 to 8 years in boys.

PMID- 15580212
TI  - Randomized trial of systemic hypothermia selectively protects the cortex on MRI
      in term hypoxic-ischemic encephalopathy.
AB  - Twenty-six infants with hypoxic-ischemic encephalopathy (HIE) were randomized to
      normothermia or to systemic hypothermia. The hypothermia group had less cortical
      gray matter signal abnormality on magnetic resonance imaging (MRI) (1/12 vs 7/14
      infants in the normothermic group; P = .036), which may indicate differing
      regional benefit from systemic hypothermia.

PMID- 15580213
TI  - Circadian and seasonal variation of first febrile seizures.
AB  - Time of occurrence of 188 first febrile seizures (FS) was recorded, both by four
      6-hour periods and by hourly intervals. The frequency of events was significantly
      ( P < .001) increased from 6 to 11.59 pm with a peak between 5 and 8 pm . A
      seasonal peak was observed in January.

PMID- 15580214
TI  - 4p terminal deletion and 11p subtelomeric duplication detected by genomic
      microarray in a patient with Wolf-Hirschhorn syndrome and an atypical phenotype.
AB  - We report a de novo cryptic 11p duplication found by genomic microarray with a
      cytogenetically detected 4p deletion. Terminal 4p deletions cause Wolf-Hirschhorn
      syndrome, but the phenotype probably was modified by the paternally derived 11p
      duplication. This emphasizes the clinical utility of genomic microarray.

PMID- 15580215
TI  - Five patients with localized facial eruptions associated with Gianotti-Crosti
      syndrome caused by primary Epstein-Barr virus infection.
AB  - Five infants exhibited an exclusively facial rash associated with Gianotti-Crosti
      syndrome(GCS). On all patient cheeks, multiple erythematous papules were seen
      symmetrically. All patients tested positive for the immunoglobulin (Ig)M antibody
      against the Epstein-Barr viral capsid antigen, suggesting that a primary Epstein
      Barr virus (EBV) infection caused localized facial rash, an alternative clinical
      picture of GCS.

PMID- 15580216
TI  - Stroke after varicella vaccination.
AB  - Two children presented with acute hemiparesis 5 days and 3 weeks following
      varicella vaccination. Both showed unilateral infarction of the basal ganglia and
      internal capsule, a distribution consistent with varicella angiopathy. Both
      children had small patent foramen ovale (PFO), and one child also had severe iron
      deficiency anemia, which may have predisposed the patient to this adverse effect.

PMID- 15580217
TI  - Clinically evident venous thromboembolic events in children with brain tumors.
AB  - We evaluated the incidence and significance of central venous access device
      dysfunction and symptomatic major thrombosis in 253 pediatric patients with brain
      tumors. Central venous access device dysfunction was a common complication
      (28.4%) and was associated with major thrombosis development and a reduced
      overall survival rate. Major thrombosis was relatively uncommon (2.8%).

PMID- 15580218
TI  - Abnormal production of tumor necrosis factor (TNF) -- alpha and clinical efficacy
      of the TNF inhibitor etanercept in a patient with PAPA syndrome [corrected].
AB  - We report a family with pyogenic sterile arthritis, pyoderna and acne syndrome
      (PAPA). The proband presented several episodes of sterile pyogenic arthritis and
      became unresponsive to glucocorticoids. After treatment with the tumor necrosis
      factor inhibitor etanercept, the disease underwent rapid and sustained clinical
      remission. Production of tumor necrosis factor-alpha by mononuclear cells of the
      proband and of the affected relatives was abnormally elevated.

PMID- 15580219
TI  - Thalidomide for severe systemic onset juvenile rheumatoid arthritis: A
      multicenter study.
AB  - Thirteen children with difficult systemic onset juvenile rheumatoid arthritis
      were treated with thalidomide. At 6 months, 11 of the 13 were able to reduce
      their use of prednisone ( P < .002), with a concurrent improvement in erythrocyte
      sedimentation rate ( P < .0001) and an increase in hemoglobin level ( P < 0.005).
      Juvenile rheumatoid arthritis improvement scores >/=50% were obtained by 10 of
      the 13 children.

PMID- 15580220
TI  - A rare complication of the closed tracheal suction system.

PMID- 15580221
TI  - Ulnar hypoplasia and neurofibromatosis type I.

PMID- 15580222
TI  - Gaucher disease phenotype.

PMID- 15580223
TI  - Childhood autoimmune cytopenia, common variable immunodeficiency, and
      sarcoidosis.

PMID- 15580224
TI  - Ghrelin, obesity and anorexia nervosa.

PMID- 15580225
TI  - Active ghrelin levels during fetal life and childhood.

PMID- 15580226
TI  - Early onset of proliferative retinopathy in patients with type I diabetes of <5
      years' duration.

PMID- 15580230
TI  - Plus ca change.

PMID- 15580231
TI  - Scientists turn anxious eyes to Bush's second term.

PMID- 15580233
TI  - Scientists divided on relevance of race in medical research.

PMID- 15580234
TI  - Despite snags and skepticism, Thai vaccine trial lumbers on.

PMID- 15580235
TI  - New technologies deliver in treating neurological diseases.

PMID- 15580236
TI  - HIV vaccine research a shot in the arm for immunologists.

PMID- 15580237
TI  - Immune response to SARS sets up puzzling paradox.

PMID- 15580239
TI  - Profile: Philippa Marrack.

PMID- 15580240
TI  - The worm has turned.

PMID- 15580242
TI  - Cancer vaccines: pessimism in check.

PMID- 15580245
TI  - Regional ethics organizations for protection of human research participants.

PMID- 15580246
TI  - Creating incentives for genomic research to improve targeting of therapies.

PMID- 15580248
TI  - West Nile virus: crossing the blood-brain barrier.

PMID- 15580249
TI  - Combination stroke therapy: easy as APC?

PMID- 15580250
TI  - Micromanaging insulin secretion.

PMID- 15580251
TI  - Cancer drug discovery: the wisdom of imprecision.

PMID- 15580252
TI  - Vitamin A helps gut T cells find their way in the dark.

PMID- 15580253
TI  - Chipping away at gallstones.

PMID- 15580255
TI  - Antibody diversity: one enzyme to rule them all.

PMID- 15580257
TI  - An innately interesting decade of research in immunology.
AB  - "Nature has provided, in the white corpuscles as you call them-in the phagocytes
      as we call them-a natural means of devouring and destroying all disease germs.
      There is at bottom only one genuinely scientific treatment for all diseases, and
      that is to stimulate the phagocytes." So opined B.B. in G.B. Shaw's The Doctor's
      Dilemma in a dramatic restatement of a key portion of Ilya Metchnikoff's Nobel
      Prize address: "Whenever the organism enjoys immunity, the introduction of
      infectious microbes is followed by the accumulation of mobile cells, of white
      corpuscles of the blood in particular which absorb the microbes and destroy them.
      The white corpuscles and the other cells capable of doing this have been
      designated 'phagocytes,' (i.e., devouring cells) and the whole function that
      ensures immunity has been given the name of 'phagocytosis'". Based on these
      insights into the foundation of resistance to infectious disease, Metchnikoff was
      awarded the 1908 Nobel Prize in Physiology or Medicine together with Paul Ehrlich
      (Fig. 1). Although both were cited for discoveries in immunity, the contributions
      of the two men seem worlds apart. Ehrlich's studies did not deal with generic
      responses to infection, but rather with the highly specific nature of antibodies
      and their relationship to the cells producing them: "As the cell receptor is
      obviously preformed, and the artificially produced antitoxin only the
      consequence, i.e. secondary, one can hardly fail to assume that the antitoxin is
      nothing else but discharged components of the cell, namely receptors discharged
      in excess". But biological systems are just that-systems-and the parts need to
      work together. And so we arrive, a century later, at an appreciation for just how
      intimately related these two seemingly disparate aspects of host defense really
      are.

PMID- 15580261
TI  - Genetically modified Plasmodium parasites as a protective experimental malaria
      vaccine.
AB  - Malaria is a mosquito-borne disease that is transmitted by inoculation of the
      Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes, transform
      into liver stages, and subsequent liver-stage development ultimately results in
      release of pathogenic merozoites. Liver stages of the parasite are a prime target
      for malaria vaccines because they can be completely eliminated by sterilizing
      immune responses, thereby preventing malarial infection. Using expression
      profiling, we previously identified genes that are only expressed in the pre
      erythrocytic stages of the parasite. Here, we show by reverse genetics that one
      identified gene, UIS3 (upregulated in infective sporozoites gene 3), is essential
      for early liver-stage development. uis3-deficient sporozoites infect hepatocytes
      but are unable to establish blood-stage infections in vivo, and thus do not lead
      to disease. Immunization with uis3-deficient sporozoites confers complete
      protection against infectious sporozoite challenge in a rodent malaria model.
      This protection is sustained and stage specific. Our findings demonstrate that a
      safe and effective, genetically attenuated whole-organism malaria vaccine is
      possible.

PMID- 15580262
TI  - Protein tagging and detection with engineered self-assembling fragments of green
      fluorescent protein.
AB  - Existing protein tagging and detection methods are powerful but have drawbacks.
      Split protein tags can perturb protein solubility or may not work in living
      cells. Green fluorescent protein (GFP) fusions can misfold or exhibit altered
      processing. Fluorogenic biarsenical FLaSH or ReASH substrates overcome many of
      these limitations but require a polycysteine tag motif, a reducing environment
      and cell transfection or permeabilization. An ideal protein tag would be
      genetically encoded, would work both in vivo and in vitro, would provide a
      sensitive analytical signal and would not require external chemical reagents or
      substrates. One way to accomplish this might be with a split GFP, but the GFP
      fragments reported thus far are large and fold poorly, require chemical ligation
      or fused interacting partners to force their association, or require coexpression
      or co-refolding to produce detectable folded and fluorescent GFP. We have
      engineered soluble, self-associating fragments of GFP that can be used to tag and
      detect either soluble or insoluble proteins in living cells or cell lysates. The
      split GFP system is simple and does not change fusion protein solubility.

PMID- 15580263
TI  - A reverse genetic, nontransgenic approach to wheat crop improvement by TILLING.
AB  - We report the use of TILLING (targeting induced local lesions in genomes), a
      reverse genetic, nontransgenic method, to improve a quality trait in a polyploid
      crop plant. Waxy starches, composed mostly of amylopectin, have unique
      physiochemical properties. Wheat with only one or two functional waxy genes
      (granule-bound starch synthase I, or GBSSI) produces starch with intermediate
      levels of amylopectin. We have identified 246 alleles of the waxy genes by
      TILLING each homoeolog in 1,920 allohexaploid and allotetraploid wheat
      individuals. These alleles encode waxy enzymes ranging in activity from near wild
      type to null, and they represent more genetic diversity than had been described
      in the preceding 25 years. A line of bread wheat containing homozygous mutations
      in two waxy homoeologs created through TILLING and a preexisting deletion of the
      third waxy homoeolog displays a near-null waxy phenotype. This approach to
      creating and identifying genetic variation shows potential as a tool for crop
      improvement.

PMID- 15580264
TI  - Coupling of ER exit to microtubules through direct interaction of COPII with
      dynactin.
AB  - Transport of proteins from the endoplasmic reticulum (ER) to the Golgi is
      mediated by the sequential action of two coat complexes: COPII concentrates cargo
      for secretion at ER export sites, then COPI is subsequently recruited to nascent
      carriers and retrieves recycling proteins back to the ER. These carriers then
      move towards the Golgi along microtubules, driven by the dynein/dynactin
      complexes. Here we show that the Sec23p component of the COPII complex directly
      interacts with the dynactin complex through the carboxy-terminal cargo-binding
      domain of p150(Glued). Functional assays, including measurements of the rate of
      recycling of COPII on the ER membrane and quantitative analyses of secretion,
      indicate that this interaction underlies functional coupling of ER export to
      microtubules. Together, our data suggest a mechanism by which membranes of the
      early secretory pathway can be linked to motors and microtubules for subsequent
      organization and movement to the Golgi apparatus.

PMID- 15580265
TI  - IAPs are functionally non-equivalent and regulate effector caspases through
      distinct mechanisms.
AB  - Some members of the inhibitor of apoptosis (IAP) family suppress apoptosis by
      neutralizing caspases. The current model suggests that all caspase-regulatory
      IAPs function as direct enzyme inhibitors, blocking effector caspases by binding
      to their catalytically active pockets. Here we show that IAPs are functionally
      non-equivalent and regulate effector caspases through distinct mechanisms.
      Whereas XIAP binds directly to the active-site pockets of effector caspases, we
      find that regulation of effector caspases by Drosophila IAP1 (DIAP1) requires an
      evolutionarily conserved IAP-binding motif (IBM) at the neo-amino terminus of the
      large caspase subunit. Remarkably, unlike XIAP, DIAP1-sequestered effector
      caspases remain catalytically active, suggesting that DIAP1 does not function as
      a bona fide enzyme inhibitor. Moreover, we demonstrate that the mammalian IAP c
      IAP1 interacts with caspase-7 in an exclusively IBM-dependent, but active site
      pocket-independent, manner that is mechanistically similar to DIAP1. The
      importance of IBM-mediated regulation of effector-caspases in vivo is
      substantiated by the enhanced apoptotic potency of IBM-mutant versions of drICE,
      DCP-1 and caspase-7.

PMID- 15580266
TI  - A critical role for cyclin E in cell fate determination in the central nervous
      system of Drosophila melanogaster.
AB  - We have examined the process by which cell diversity is generated in neuroblast
      (NB) lineages in the central nervous system of Drosophila melanogaster. Thoracic
      NB6-4 (NB6-4t) generates both neurons and glial cells, whereas NB6-4a generates
      only glial cells in abdominal segments. This is attributed to an asymmetric first
      division of NB6-4t, localizing prospero (pros) and glial cell missing (gcm) only
      to the glial precursor cell, and a symmetric division of NB6-4a, where both
      daughter cells express pros and gcm. Here we show that the NB6-4t lineage
      represents the ground state, which does not require the input of any homeotic
      gene, whereas the NB6-4a lineage is specified by the homeotic genes abd-A and Abd
      B. They specify the NB6-4a lineage by down-regulating levels of the G1 cyclin,
      DmCycE (CycE). CycE, which is asymmetrically expressed after the first division
      of NB6-4t, functions upstream of pros and gcm to specify the neuronal sublineage.
      Loss of CycE function causes homeotic transformation of NB6-4t to NB6-4a, whereas
      ectopic CycE induces reverse transformations. However, other components of the
      cell cycle seem to have a minor role in this process, suggesting a critical role
      for CycE in regulating cell fate in segment-specific neural lineages.

PMID- 15580267
TI  - Akt and 14-3-3eta regulate Miz1 to control cell-cycle arrest after DNA damage.
AB  - The transcription factor Miz1 is required for DNA-damage-induced cell-cycle
      arrest. We have now identified 14-3-3eta as a gene that inhibits Miz1 function
      through interaction with its DNA binding domain. Binding of 14-3-3eta to Miz1
      depends on phosphorylation by Akt and regulates the recovery of cells from arrest
      after DNA damage. Miz1 has two functions in response to DNA damage: first, it is
      required for upregulation of a large group of genes, a function that is regulated
      by c-Myc, but not by 14-3-3eta; second, Miz1 represses the expression of many
      genes in response to DNA damage in an Akt- and 14-3-3eta-regulated manner.

PMID- 15580268
TI  - Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin
      dependent actin dynamics.
AB  - Cofilin is a key regulator of actin cytoskeletal dynamics whose activity is
      controlled by phosphorylation of a single serine residue. We report the
      biochemical isolation of chronophin (CIN), a unique cofilin-activating
      phosphatase of the haloacid dehalogenase (HAD) superfamily. CIN directly
      dephosphorylates cofilin with high specificity and colocalizes with cofilin in
      motile and dividing cells. Loss of CIN activity blocks phosphocycling of cofilin,
      stabilizes F-actin structures and causes massive cell division defects. Our
      findings identify a physiological phospho-serine protein substrate for a
      mammalian HAD-type phosphatase and demonstrate that CIN is an important novel
      regulator of cofilin-mediated actin reorganization.

PMID- 15580269
TI  - Traveling waves of activity in primary visual cortex during binocular rivalry.
AB  - When the two eyes view large, dissimilar patterns that induce binocular rivalry,
      alternating waves of visibility are experienced as one pattern sweeps the other
      out of conscious awareness. Here we combine psychophysics with functional
      magnetic resonance imaging to show tight linkage between dynamics of perceptual
      waves during rivalry and neural events in human primary visual cortex (V1).

PMID- 15580270
TI  - The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons
      transduces mechanical signals.
AB  - Transformation of mechanical energy into ionic currents is essential for touch,
      hearing and nociception. Although DEG/ENaC proteins are believed to form sensory
      mechanotransduction channels, the evidence for this role remains indirect. By
      recording from C. elegans touch receptor neurons in vivo, we found that external
      force evokes rapidly activating mechanoreceptor currents (MRCs) carried mostly by
      Na(+) and blocked by amiloride-characteristics consistent with direct mechanical
      gating of a DEG/ENaC channel. Like mammalian Pacinian corpuscles, these neurons
      depolarized with both positive and negative changes in external force but not
      with sustained force. Null mutations in the DEG/ENaC gene mec-4 and in the
      accessory ion channel subunit genes mec-2 and mec-6 eliminated MRCs. In contrast,
      the genetic elimination of touch neuron-specific microtubules reduced, but did
      not abolish, MRCs. Our findings link the application of external force to the
      activation of a molecularly defined metazoan sensory transduction channel.

PMID- 15580271
TI  - Electrical synapses coordinate activity in the suprachiasmatic nucleus.
AB  - In the suprachiasmatic nucleus (SCN), the master circadian pacemaker, neurons
      show circadian variations in firing frequency. There is also considerable
      synchrony of spiking across SCN neurons on a scale of milliseconds, but the
      mechanisms are poorly understood. Using paired whole-cell recordings, we have
      found that many neurons in the rat SCN communicate via electrical synapses.
      Spontaneous spiking was often synchronized in pairs of electrically coupled
      neurons, and the degree of this synchrony could be predicted from the magnitude
      of coupling. In wild-type mice, as in rats, the SCN contained electrical
      synapses, but electrical synapses were absent in connexin36-knockout mice. The
      knockout mice also showed dampened circadian activity rhythms and a delayed onset
      of activity during transition to constant darkness. We suggest that electrical
      synapses in the SCN help to synchronize its spiking activity, and that such
      synchrony is necessary for normal circadian behavior.

PMID- 15580272
TI  - Silencing of unsynapsed meiotic chromosomes in the mouse.
AB  - In Neurospora, DNA unpaired in meiosis both is silenced and induces silencing of
      all DNA homologous to it. This process, called meiotic silencing by unpaired DNA,
      is thought to protect the host genome from invasion by transposable elements. We
      now show that silencing of unpaired (unsynapsed) chromosome regions also takes
      place in the mouse during both male and female meiosis. The tumor suppressor
      protein BRCA1 is implicated in this silencing, mirroring its role in the meiotic
      silencing of the X and Y chromosomes in normal male meiosis. These findings
      impact on the interpretation of the relationship between synaptic errors and
      sterility in mammals and extend our understanding of the biology of Brca1.

PMID- 15580273
TI  - Locus 'decontraction' and centromeric recruitment contribute to allelic exclusion
      of the immunoglobulin heavy-chain gene.
AB  - Allelic exclusion of immunoglobulin genes ensures the expression of a single
      antibody molecule in B cells through mostly unknown mechanisms. Large-scale
      contraction of the immunoglobulin heavy-chain (Igh) locus facilitates
      rearrangements between Igh variable (V(H)) and diversity gene segments in pro-B
      cells. Here we show that these long-range interactions are mediated by 'looping'
      of individual Igh subdomains. The Igk locus also underwent contraction by looping
      in small pre-B and immature B cells, demonstrating that immunoglobulin loci are
      in a contracted state in rearranging cells. Successful Igh recombination induced
      the rapid reversal of locus contraction in response to pre-B cell receptor
      signaling, which physically separated the distal V(H) genes from the proximal Igh
      domain, thus preventing further rearrangements. In the absence of locus
      contraction, only the four most proximal V(H) genes escaped allelic exclusion in
      immature mu-transgenic B lymphocytes. Pre-B cell receptor signaling also led to
      rapid repositioning of one Igh allele to repressive centromeric domains in
      response to downregulation of interleukin 7 signaling. These data link both locus
      'decontraction' and centromeric recruitment to the establishment of allelic
      exclusion at the Igh locus.

PMID- 15580275
TI  - Enhanced spin accumulation and novel magnetotransport in nanoparticles.
AB  - Spin injection and accumulation are key phenomena supporting a variety of
      concepts for spin-electronic devices. These phenomena are expected to be enhanced
      in nanoparticles over bulk structures due to their discrete energy levels and
      large charging energies. In this article, precise magnetotransport measurements
      in the single-electron tunnelling regime are performed by preparing appropriate
      microfabricated devices containing cobalt nanoparticles. Here we provide
      experimental evidence for characteristic features of spin accumulation in
      magnetic nanoparticles, such as oscillations of the magnetoresistance with a
      periodical sign change as a function of bias voltage. Theoretical analysis of the
      magnetoresistance behaviour clearly shows that the spin-relaxation time in
      nanoparticles is highly enhanced in comparison with that in the bulk.

PMID- 15580276
TI  - Rapid spontaneous accessibility of nucleosomal DNA.
AB  - DNA wrapped in nucleosomes is sterically occluded, creating obstacles for
      proteins that must bind it. How proteins gain access to DNA buried inside
      nucleosomes is not known. Here we report measurements of the rates of spontaneous
      nucleosome conformational changes in which a stretch of DNA transiently unwraps
      off the histone surface, starting from one end of the nucleosome, and then
      rewraps. The rates are rapid. Nucleosomal DNA remains fully wrapped for only
      approximately 250 ms before spontaneously unwrapping; unwrapped DNA rewraps
      within approximately 10-50 ms. Spontaneous unwrapping of nucleosomal DNA allows
      any protein rapid access even to buried stretches of the DNA. Our results explain
      how remodeling factors can be recruited to particular nucleosomes on a
      biologically relevant timescale, and they imply that the major impediment to
      entry of RNA polymerase into a nucleosome is rewrapping of nucleosomal DNA, not
      unwrapping.

PMID- 15580277
TI  - Crystal structure of a phage Twort group I ribozyme-product complex.
AB  - Group I introns are catalytic RNAs capable of orchestrating two sequential
      phosphotransesterification reactions that result in self-splicing. To understand
      how the group I intron active site facilitates catalysis, we have solved the
      structure of an active ribozyme derived from the orf142-I2 intron from phage
      Twort bound to a four-nucleotide product RNA at a resolution of 3.6 A. In
      addition to the three conserved domains characteristic of all group I introns,
      the Twort ribozyme has peripheral insertions characteristic of phage introns.
      These elements form a ring that completely envelops the active site, where a snug
      pocket for guanosine is formed by a series of stacked base triples. The structure
      of the active site reveals three potential binding sites for catalytic metals,
      and invokes a role for the 2' hydroxyl of the guanosine substrate in organization
      of the active site for catalysis.

PMID- 15580278
TI  - What is the clinical significance of positive blood cultures with Aspergillus sp
      in hematopoietic stem cell transplant recipients? A 23 year experience.
AB  - Hematopoietic stem cell (HSC) transplantation is the most frequent underlying
      predisposing condition to invasive aspergillosis. However, the significance of
      positive blood culture with Aspergillus sp in this particular population remains
      uncertain. We retrospectively reviewed all blood cultures performed in 1453
      patients who received HSC transplant at our institution between 1980 and 2002. We
      identified 19 patients with positive blood cultures with Aspergillus sp. Only one
      of these patients had clinical, histologic or microbiologic evidence of invasive
      aspergillosis. Thus, even in a population at highest risk for invasive
      aspergillosis, positive blood cultures with Aspergillus sp remain unusual, and
      cannot be readily associated with invasive aspergillosis. A case by case
      assessment by treating physicians of the clinical and radiologic parameters
      should be systematically made to establish the significance of aspergillemia.
      Single bottle positivity, obtained with the lysis-centrifugation blood culture
      system, is a common indicator of pseudoaspergillemia.

PMID- 15580279
TI  - Patient-rated emotional and physical functioning among hematologic cancer
      patients during hospitalization for stem-cell transplantation.
AB  - In this 3-year prospective inpatient study, 220 patients received stem-cell
      transplantation (SCT) for hematologic cancer at a single institution. The
      objective of the study is to provide data on patient-rated emotional (depression
      and anxiety) and physical (overall physical status, energy level, and systemic
      symptomatology) functioning during hospitalization for SCT and to compare whether
      these differ between autologous and allogeneic SCT. Patients were assessed at
      hospital admission (T1), day of SCT (T2), and 7 days (T3) and 14 days (T4) after
      SCT, yielding a total of 852 evaluations. For the overall sample, anxiety was
      highest at T1 and decreased afterwards; a marked worsening in physical health
      status variables corresponded with a sharp increase in depression from T1 to T3,
      and was followed by an improvement in physical health and a reduction of
      depression. Compared to allogeneic SCT, a better physical outcome for autologous
      SCT was demonstrated by the significant group effect for systemic symptomatology
      and by the significant group x time interaction for overall physical status and
      energy level; there were no significant differences in depression or anxiety
      between SCT groups. These findings have implications for treatment decision
      making, coping with the transplantation process, and improving prevention and
      treatment strategies.

PMID- 15580280
TI  - Transplantation of allogeneic CD34-selected stem cells after fludarabine-based
      conditioning regimen for children with mucopolysaccharidosis 1H (M. Hurler).
AB  - Hurler syndrome (MPS1H) is a progressive inborn error of mucopolysaccharide
      metabolism leading to premature death. Allogeneic hematopoietic cell
      transplantation (HCT) can achieve stabilization and improve long-term survival.
      However, large studies have shown that preparative regimen-related toxicity (RRT)
      and graft failure rates have been relatively high. We transplanted five Hurler
      children with a fludarabine-based conditioning regimen, consisting of
      fludarabine/busulphan/ATG for matched family donor (MFD), with the addition of
      melphalan for mismatched family donor and matched unrelated donor (MUD)
      transplantations. Median age at HCT was 27 months (range 10-36). The source of
      stem cells was bone marrow in one MFD and CD34-selected PBSC in four patients.
      Median CD34+ cell dose was 25 x 10(6)/kg (range 11.5-54). No RRT > grade II was
      observed. All patients are surviving at a median of 32 months (range 14-41) and
      show sustained donor engraftment with 3/5 having full donor chimerism, and 2/5
      mixed chimerism (> 85%). We conclude that this regimen is feasible and has low
      toxicity in Hurler children. In combination with high doses of CD34+ selected
      cells (> 10 x 10(6)/kg) and donor lymphocyte infusions, stable engraftment could
      be achieved in unrelated and mismatched related transplantations.

PMID- 15580281
TI  - Can the stem cell mobilization technique influence CD34+ cell collection
      efficiency of leukapheresis procedures in patients with hematologic malignancies?
AB  - A total of 415 leukaphereses in 201 patients stimulated with growth factor (GF; n
      = 119) or chemotherapy-GF (n = 296) were studied to determine CD34+ cell
      collection efficiency (CE). The pre-apheresis leukocyte count was 1-93 x 10(9)/l
      (median 20), and peripheral blood CD34 count (PBCD34) was 1-1104/microl (median
      19). The total number of CD34+ cells collected was 4-6531 x 10(6) (median 151);
      corresponding to 0.1-111.4 x 10(6) (median 2.3) per kg. There was strong
      correlation between PBCD34 and the number of CD34+ cells collected (r = 0.9; P <
      0.0001). CE was 7-145% (median 46). On multiple regression analysis, a higher
      leukocyte count (P < 0.0001) was the most important predictor of lower CE. CE
      with leukocytes < 20 was 7-145% (median 53%) compared to 10-132% (median 40%)
      with leukocyte > or = 20 (P < 0.0001). In all, 61% of the apheresis procedures
      performed after chemotherapy-GF occurred when leukocytes were < 20 compared to
      21% of those performed after GF alone (P < 0.0001). We conclude that mobilizing
      patients with the combination of chemotherapy and GF rather than GF alone leads
      to leukapheresis being performed when the leukocyte count is low -- in a range
      that results in optimum CD34+ cell CE. Autologous stem cells should be mobilized
      with chemotherapy-GF rather than GF alone whenever possible.

PMID- 15580282
TI  - CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow
      transplantation for advanced AML using busulfan-based preparative regimens.
AB  - The role of T-cell depletion (TCD) to prevent graft-versus-host disease (GVHD)
      after matched unrelated donor allogeneic bone marrow transplant (MUD BMT) remains
      undefined. Most studies employ total body irradiation and pan TCD. Between March
      1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML)
      patients with busulfan-based preparative regimens and selective TCD. The
      preparative regimen consisted of busulfan 14 mg/kg, cyclophosphamide 120 mg/kg
      and VP-16 50 mg/kg in all but one patient who only received busulfan and
      cyclophosphamide. Donor marrow was depleted of CD8+ T cells by immunomagnetic
      bead separation. The patients were also treated with cyclosporine and
      methylprednisolone or FK-506 and mini-dose methotrexate. Four (15%) of 33
      patients developed graft failure or rejection. However, three of these patients
      were serologically mismatched at HLA-Cw. Although 67% of evaluable patients
      developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%. The
      severity of acute GVHD correlated with the degree of CD8+ TCD. Median relapse
      free survival was 5 months among 20 patients treated with active AML, and 28
      months among 13 patients treated in complete remission. Our results confirm that
      MUD BMT with CD8+ TCD for AML is a potentially curative treatment option.

PMID- 15580283
TI  - Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal
      and malignant tissues.
AB  - FATE/BJ-HCC-2 is a newly identified cancer/testis (CT) antigen, which was
      detected in tumor tissues and testis. As previous studies of FATE/BJ-HCC-2
      expression pattern were mainly based on messenger RNA (mRNA) analysis, it is
      necessary to investigate its actual protein expression pattern in tumor tissues
      for the evaluation of its application value. In this study, we produced specific
      polyclonal antibody (pAb) to the recombinant FATE/BJ-HCC-2 protein and analyzed
      the FATE/BJ-HCC-2 antigen expression in normal and malignant tissues by the
      immunohistochemical approach. The results showed that there was no detectable
      FATE/BJ-HCC-2 antigen expressed in normal tissues except testis. In
      hepatocellular carcinoma (HCC) tissues, the FATE/BJ-HCC-2 antigen was detected in
      20% (7/35) specimens. All samples that expressed the FATE/BJ-HCC-2 antigen were
      of poorly or moderately differentiated HCC. The stained antigen was located in
      the cytoplasm and the staining pattern showed heterogeneity from focal to more
      than 40% of the tumor cells. The FATE/BJ-HCC-2 antigen was also expressed in
      other tumor tissues. The results of [3H]thymidine incorporation showed that
      FATE/BJ-HCC-2 protein enhanced tumor cell proliferation after transfection of
      FATE/BJ-HCC-2 gene in HCC cell line (P<0.01). This effect could be specifically
      blocked by anti-FATE/BJ-HCC-2 pAb. Serological screening showed that the antibody
      specific to the FATE/BJ-HCC-2 antigen was detected in 7.7% (4/52) patients.
      Notably, the four positive patients bore poorly or moderately differentiated HCC.
      FATE/BJ-HCC-2 mRNA transcript was detected in the peripheral blood mononuclear
      cells (PBMCs) of 46.67% patients whose resected HCC tissue samples were positive
      for FATE/BJ-HCC-2 mRNA, which implicated tumor cell dissemination in blood
      circulation and may relate to the metastasis of HCC. Thus, FATE/BJ-HCC-2 may be a
      valuable candidate CT antigen for polyvalent vaccines in tumor immunotherapy and
      an assisting diagnostic marker for prognosis of the disease.

PMID- 15580284
TI  - Loss of heterozygosity on chromosome 22q in gastrointestinal stromal tumors
      (GISTs): a study on 50 cases.
AB  - Mutational activation of KIT or PDGFRA is considered an early step in
      pathogenesis of gastrointestinal stromal tumors (GISTs); however, other nonrandom
      genetic changes have also been identified. At least three common regions of
      deletions on chromosome 22q, which may harbor putative tumor suppressor genes,
      have been defined. However, mapping of these regions has been inconsistent. It
      has also been speculated that GI autonomous nerve tumors (GANTs), GISTs with
      ultrastructural features suggestive of autonomic nerve differentiation, are
      characterized by a specific deletion involving 22q13 cytogenetic region. This
      study was undertaken to evaluate loss of heterozygosity (LOH) on chromosome 22q
      in 50 GISTs, including 10 GANTs. Four tumors were incidental minimal lesions
      <or=10 mm in diameter. LOH was evaluated using 20 PCR-based microsatellite
      markers and capillary gel electrophoresis. In all, 15 (30%) cases showed LOH of
      more than 75% of informative markers, suggesting loss of chromosome 22q. A total
      of 24 GISTs (50%) revealed LOH of one to seven informative markers clustered in
      different loci suggesting simultaneous involvement of different regions. The
      highest frequency of LOH was seen at D22S922 and D22S425, mapped to 22q13.33 and
      22q11.22, respectively. However, LOH at other regions including IL2RB and NF2
      locus was also found. No NF2 mutations were identified in four analyzed tumors.
      LOH on chromosome 22q was more frequent among intestinal than among gastric
      GISTs; however, there was no difference between LOH pattern seen in tumors
      defined by different histologic, ultrastructural (GANT) and molecular features
      (KIT and PDGFRA mutations). Although minimal GISTs revealed LOH on chromosome
      22q, there was a higher LOH frequency in malignant than in benign tumors. An
      isolated LOH at D22S425 was equally found in both benign and malignant tumors.
      These observations may suggest that LOHs on chromosome 22q in GISTs play a role
      in early stages of tumor formation as well as in late tumor progression.

PMID- 15580285
TI  - Disruption of IFT results in both exocrine and endocrine abnormalities in the
      pancreas of Tg737(orpk) mutant mice.
AB  - While relatively ignored for years as vestigial, cilia have recently become the
      focus of intense interest as organelles that result in severe pathologies when
      disrupted. Here, we further establish a connection between cilia dysfunction and
      disease by showing that loss of polaris (Tg737), an intraflagellar transport
      (IFT) protein required for ciliogenesis, causes abnormalities in the exocrine and
      endocrine pancreas of the Tg737(orpk) mouse. Pathology is evident late in
      gestation as dilatations of the pancreatic ducts that continue to expand
      postnatally. Shortly after birth, the acini become disorganized, undergo
      apoptosis, and are largely ablated in late stage pathology. In addition, serum
      amylase levels are elevated and carboxypeptidase is abnormally activated within
      the pancreas. Ultrastructural analysis reveals that the acini undergo extensive
      vacuolization and have numerous 'halo-granules' similar to that seen in induced
      models of pancreatitis resulting from duct obstruction. Intriguingly, although
      the acini are severely affected in Tg737(orpk) mutants, cilia and Tg737
      expression are restricted to the ducts and islets and are not detected on acinar
      cells. Analysis of the endocrine pancreas in Tg737(orpk) mutants revealed normal
      differentiation and distribution of cell types in the islets. However, after
      fasting, mutant blood glucose levels are significantly lower than controls and
      when challenged in glucose tolerance tests, Tg737(orpk) mutants exhibited defects
      in glucose uptake. These findings are interesting in light of the recently
      proposed role for polaris, the protein encoded by the Tg737 gene, in the hedgehog
      pathway and hedgehog signaling in insulin production and glucose homeostasis.

PMID- 15580286
TI  - HDPR1, a novel inhibitor of the WNT/beta-catenin signaling, is frequently
      downregulated in hepatocellular carcinoma: involvement of methylation-mediated
      gene silencing.
AB  - Oncogenic activation of the WNT/beta-catenin signaling pathway is common in
      hepatocellular carcinoma (HCC). Dishevelled (Dvl), a key activator of the
      pathway, inhibits the adenomatous polyposis coli complex, and this leads to the
      accumulation of beta-catenin and promotes tumorigenesis. Recently, a novel
      inhibitor of Dishevelled, namely Dapper (Dpr), was isolated in Xenopus. To
      explore whether HDPR1, the human homologue of Dpr, has an anti-oncogenic role in
      hepatocarcinogenesis, we studied the expression of this gene in HCCs. We found
      that there were two alternatively spliced transcripts of HDPR1, designated as
      alpha and beta forms, in human liver. Downregulation of the gene expression was
      observed in 31 (43%) of the 72 human HCC samples using the primer pair that
      amplified both transcripts. Furthermore, the HDPR1alpha was downregulated in 42
      (58%) of 72 human HCCs and the downregulation significantly correlated with
      accumulation of beta-catenin. Also, downregulation of HDPR1 by RNA interference
      in HLE cells led to cytoplasmic accumulation of beta-catenin. Furthermore, a CpG
      island located at the promoter region and exon 1 of the HDPR1 gene was methylated
      in 22 (51%) of human HCCs. We showed that downregulation of HDPR1, in hepatoma
      cell lines, was associated with methylation of this CpG island using bisulfite
      sequencing and 5-aza-2'-deoxycytidine demethylation experiment. In addition to
      methylation-mediated downregulation of HDPR1, allelic loss (13-28% of informative
      cases) was detected using microsatellite markers flanking the HDPR1 locus. To
      conclude, downregulation of HDPR1 is common in HCCs, frequently involves
      hypermethylation of the promoter region, and allelic loss of the HDPR1 locus may
      also play a role.

PMID- 15580287
TI  - c-Myc activation by Theileria parasites promotes survival of infected B
      lymphocytes.
AB  - Theileria parasites infect and transform bovine lymphocytes, but host cell
      immortalization is reversible, as upon parasite death the lymphocytes rapidly die
      of apoptosis. Infection leads to a marked augmentation in the levels of
      lymphocyte c-Myc, and the parasite achieves this by inducing increased c-myc
      transcription and by prolonging the half-life of the transcription factor.
      Reduction in c-Myc turnover can be ascribed to CK2-mediated phosphorylation of
      the transcription factor. A parasite-dependent GM-CSF autocrine loop activates a
      JAK2/STAT3 signalling pathway that contributes to heightened c-myc transcription,
      and inhibition of the pathway leads to caspase 9 activation and apoptosis that
      can be directly ascribed to a reduction in c-Myc. An antiapoptotic role for c-Myc
      was clearly demonstrated by specific inhibition of c-myc expression with
      antisense oligonucleotides, and this correlates with loss of the antiapoptotic
      protein Mcl-1, and, consistently, ectopic expression of c-Myc abrogates B-cell
      death induced upon JAK2 inhibition. Thus, Theileria parasites ensure the survival
      of their host lymphocytes via specific activation of c-Myc.

PMID- 15580288
TI  - Cell cycle-dependent nucleocytoplasmic shuttling of the neurofibromatosis 2
      tumour suppressor merlin.
AB  - The neurofibromatosis 2 tumour suppressor merlin/schwannomin is structurally
      related to the ezrin-radixin-moesin family of proteins, which anchor actin
      cytoskeleton to specific membrane proteins and participate in cell signalling.
      Merlin inhibits cell growth with a yet unknown mechanism. As most tumour
      suppressors are linked to cell cycle control, we investigated merlin's behaviour
      during cell cycle. In glioma and osteosarcoma cells, endogenous merlin was
      targeted to the nucleus in a cell cycle-specific manner. Merlin accumulated
      perinuclearly at the G2/M phase, and shifted to the nucleus at early G1. During
      mitosis, merlin localized to mitotic spindles and at the contractile ring.
      Nuclear merlin was strongly reduced in confluent cells. Blocking of the
      CRM1/exportin nuclear export pathway led to accumulation of merlin in the
      nucleus. Activation of the p21-activated kinase or protein kinase A, which result
      in phosphorylation of merlin, did not affect its nuclear localization. Merlin
      regulates the activity of extracellular signal-regulated kinase 2 (ERK2) and
      nuclear localization of both proteins was induced by cell adhesion. Unlike ERK2,
      nuclear localization of merlin was not, however, dependent on intact actin
      cytoskeleton. These results link merlin to events related to cell cycle control
      and may help to resolve its tumour suppressor function.

PMID- 15580289
TI  - Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2,
      regulates cyclin D1/PRAD1 expression.
AB  - Parafibromin is the 531-amino-acid protein product encoded by HRPT2, a putative
      tumor suppressor gene recently implicated in the autosomal dominant
      hyperparathyroidism-jaw tumor familial cancer syndrome, sporadic parathyroid
      cancer, and a minority of families with isolated hyperparathyroidism.
      Parafibromin contains no identified functional domains but bears sequence
      homology to Cdc73p, a budding yeast protein component of the RNA polymerase II
      associated Paf1 complex. This study addressed the expression and functional
      properties of human parafibromin. A survey of human and mouse tissues analysed
      with polyclonal antibodies to parafibromin showed specific immunoreactivity in
      adrenal and parathyroid glands, kidney, heart, and skeletal muscle. Subcellular
      fractionation and laser confocal microscopy of normal human parathyroid gland
      demonstrated expression of parafibromin in both the cytoplasmic and nuclear
      compartments. Parafibromin was expressed in four parathyroid adenomas but was
      absent from two parathyroid carcinomas. Transient overexpression of wild-type
      parafibromin, but not its Leu64Pro missense mutant implicated in parathyroid
      cancer and familial isolated hyperparathyroidism, inhibited cell proliferation,
      and blocked expression of cyclin D1, a key cell cycle regulator previously
      implicated in parathyroid neoplasia. These results demonstrate that human
      parafibromin is a nucleocytoplasmic protein with functions consistent with its
      postulated role as a tumor suppressor protein.

PMID- 15580290
TI  - Identification of a novel centrosome/microtubule-associated coiled-coil protein
      involved in cell-cycle progression and spindle organization.
AB  - Here we describe the identification of a novel vertebrate-specific
      centrosome/spindle pole-associated protein (CSPP) involved in cell-cycle
      regulation. The protein is predicted to have a tripartite domain structure, where
      the N- and C-terminal domains are linked through a coiled-coil mid-domain.
      Experimental analysis of the identified domains revealed that spindle association
      is dependent on the N-terminal and the coiled-coil mid domain. The expression of
      CSPP at the mRNA level was detected in all tested cell lines and in testis
      tissue. Ectopic expression of CSPP in HEK293T cells blocked cell-cycle
      progression in early G1 phase and in mitosis in a dose-dependent manner.
      Interestingly, mitosis-arrested cells contained aberrant spindles and showed
      impairment of chromosome congression. Inhibition of CSPP gene expression by small
      interfering RNAs induced cell-cycle arrest/delay in S phase. This phenotype was
      characterized by elevated levels of cyclin A, decreased levels of cyclin E and
      hyperphosphorylation of the S-phase checkpoint kinase Chk1. The activation of
      Chk1 may indicate a replication stress response due to an inappropriate G1/S
      phase transition. Taken together, we demonstrate that CSPP is associated with
      centrosomes and microtubules and may play a role in the regulation of G(1)/S
      phase progression and spindle assembly.

PMID- 15580291
TI  - Regulation of cyclin D1 expression by autocrine IGF-I in human BON neuroendocrine
      tumour cells.
AB  - Constitutive expression of cyclin D1 is a frequent abnormality in human cancer
      and sustains the transformed phenotype. We have previously demonstrated that
      cyclin D1 is constitutively expressed in human BON neuroendocrine tumour cells
      due to an autocrine insulin-like growth factor-I (IGF-I) loop. Here we examine
      the regulation of cyclin D1 expression by endogenously released IGF-I in BON
      cells. Cyclin D1 expression in these cells was found to be dependent on
      phosphatidylinositol 3-kinase (PI3-K), but independent of the extracellular
      signal-regulated kinase cascade. Ras- and Rac-GTPases were found to be upstream
      activators of cyclin D1 expression, whereas protein kinase B/AKT and nuclear
      factor kappa B (NFkappaB) could be established as downstream mediators of cyclin
      D1 transcription in response to endogenously released IGF-I in these cells. In
      addition, the Ras/PI3-K/AKT/Rac/NFkappaB/cyclin D1 signaling cascade triggered by
      endogenously released IGF-I is sufficient to sustain Rb phosphorylation and cdk4
      kinase activity in BON cells. In conclusion, our data provide the first
      comprehensive map of the signaling events elicited by endogenously released IGF-I
      leading to constitutive cyclin D1 expression in human neuroendocrine tumour
      cells.

PMID- 15580292
TI  - A network of clinically and functionally relevant genes is involved in the
      reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after
      transfer of human chromosome 8.
AB  - Several investigations have supposed that tumor suppressor genes might be located
      on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into
      MDA-MB-231 breast cancer cells and generated independent hybrids with strongly
      reduced tumorigenic potential. Loss of the transferred chromosome results in
      reappearance of the malignant phenotype. Expression analysis identified a set of
      109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to
      the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are
      differentially expressed in human breast tumors. The expression pattern of CT8-ps
      was associated with prognostic factors such as tumor size and grading as well as
      loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps
      networks suggesting that these genes act cooperatively to cause reversion of
      tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and
      experimental system to identify and evaluate genes and gene networks involved in
      the development and/or progression of breast cancer.

PMID- 15580293
TI  - Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA
      translation.
AB  - Deregulated c-myc gene expression is associated with many human and animal
      cancers. Myc overexpression promotes the growth of blood and lymphatic vessels,
      which is due in part to induction of growth factors including vascular
      endothelial growth factor (VEGF). We determined that the P493-6 human B-cell line
      increases VEGF production 10-fold upon Myc overexpression. Myc overexpression in
      avian B cells similarly resulted in high level VEGF production. Real-time RT-PCR
      analyses showed that Myc did not alter the VEGF mRNA content of these cell lines,
      indicating that a post-transcriptional mechanism regulates VEGF production. VEGF
      mRNA translation was examined by RT-PCR analysis of monosome and polysome sucrose
      gradient fractions from Myc-on and Myc-off P493-6 cells. Myc increased VEGF mRNA
      translation initiation, as VEGF mRNA loading onto polysomes increased 14-fold in
      Myc-on cells, and the number of ribosomes loaded per VEGF mRNA increased
      threefold. This translational regulation is specific to VEGF mRNA, as total
      polysomes show the same sucrose gradient profile in Myc-on and Myc-off cells,
      with no change in the percent ribosomes in polysomes, or in the number of
      ribosomes per polysomal mRNA. Myc stimulates VEGF production by a rapamycin- and
      LY294002-sensitive pathway, which does not involve alteration of eIF4E activity.

PMID- 15580294
TI  - Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell
      leukemia.
AB  - Retroviral insertions that activate proto-oncogenes are a primary cause of tumors
      in certain strains of mice. The AKXD recombinant inbred mice are predisposed to a
      variety of leukemias and lymphomas as a result of viral integration. One common
      insertion site, the ecotropic viral insertion site 3 (Evi3), has been implicated
      in most B-cell tumors in the AKXD-27 strain. The Evi3 gene encodes a zinc-finger
      protein with sequence similarity to the Early B-cell Factor-Associated Zinc
      finger gene (EBFAZ). We show that the Evi3 gene is overexpressed in several
      tumors with viral insertions at Evi3, which results in the upregulation of Early
      B-cell Factor (EBF)-target gene expression, suggesting that Evi3 modulates EBF
      activity. Reconstitution of primary leukemia cells showed that these tumors
      express high densities of the B-cell surface proteins CD19 and CD38, which are
      EBF targets. Using a transactivation assay, we show that the terminal six zinc
      fingers of Evi3 are required for modification of EBF activity. This is the first
      evidence that Evi3 expression in tumors alters the level of EBF target genes, and
      the first characterization of the Evi3 protein domains required for modulation of
      EBF activity. Further, these data imply that Evi3 misexpression initiates
      tumorigenesis by perturbing B-cell development via an interaction with EBF.

PMID- 15580295
TI  - Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired
      ductal outgrowth.
AB  - The ErbB2 receptor tyrosine kinase has been implicated as a critical growth
      factor receptor in both normal development and cancer. Amplification and
      overexpression of this receptor is observed in 20-30% of all human breast cancers
      and is inversely correlated with patient survival. Studies with transgenic mice
      have established that elevated expression of erbB2 in mammary epithelium can
      directly induce mammary carcinomas. Although these studies confirmed a role for
      ErbB2 in breast cancer induction, the precise role of ErbB2 in normal mammary
      gland development remained to be elucidated due to the embryonic lethality
      associated with the null mutation. Here, we demonstrate that the mammary-specific
      ablation of erbB2 through Cre-mediated recombination leads to a striking ductal
      elongation defect. In addition to the observed elongation defect, we noted that
      branching in the adult mammary gland was also reduced. Despite these
      perturbations in virgin mammary gland morphogenesis, targeted disruption of erbB2
      had little impact on the ability of these animals to lactate. Taken together,
      these observations indicate that erbB2 plays a critical role in the initial
      stages of mammary gland morphogenesis.

PMID- 15580296
TI  - RNA interference against a glioma-derived allele of EGFR induces blockade at G2M.
AB  - Amplification and mutation of the epidermal growth factor receptor (EGFR) is
      common in astrocytoma. The most frequently occurring mutation (DeltaEGFR,
      EGFRvIII) deletes exons 2-7 from this receptor tyrosine kinase (RTK), and signals
      constitutively in the absence of ligand. DeltaEGFR is not found in normal tissue,
      and therefore represents an attractive therapeutic target. Here, we show that a
      small interfering RNA (siRNA) directed against the unique exon 1/exon 8 junction
      sequence of DeltaEGFR efficiently suppressed expression of DeltaEGFR in rodent
      fibroblasts and in two human glioblastoma cell lines. SiRNA-mediated depletion of
      DeltaEGFR led to reduction in the levels of phosphorylated Akt in glioma cells,
      was associated with increased apoptosis, and induced partial arrest at the G2M
      phase of the cell cycle. Inhibitors of PI3 kinase cooperated with siRNA
      treatment, leading to further increases in both cell cycle blockade and
      apoptosis. Importantly, cell cycle blockade could be reversed, and apoptosis
      rescued using a conditional allele of Akt, implicating Akt as a primary target of
      combination therapy. This study demonstrates the therapeutic potential of siRNA
      to impact DeltaEGFR as a glioma-specific target, and offers a mechanistic
      rationale for combining siRNA and small molecule inhibitor therapies against
      distinct components in the EGFR signaling pathway.

PMID- 15580297
TI  - Sumoylation of the net inhibitory domain (NID) is stimulated by PIAS1 and has a
      negative effect on the transcriptional activity of Net.
AB  - Net (Elk-3, Sap-2, Erp) and the related ternary complex factors Elk-1 and Sap-1
      are effectors of multiple signalling pathways at the transcriptional level and
      play a key role in the dynamic regulation of gene expression. Net is distinct
      from Elk-1 and Sap-1, in that it is a strong repressor of transcription that is
      converted to an activator by the Ras/Erk signalling pathway. Two autonomous
      repression domains of Net, the NID and the CID, mediate repression. We have
      previously shown that the co-repressor CtBP is implicated in repression by the
      CID. In this report we show that repression by the NID involves a different
      pathway, sumoylation by Ubc9 and PIAS1. PIAS1 interacts with the NID in the two
      hybrid assay and in vitro. Ubc9 and PIAS1 stimulate sumoylation in vivo of lysine
      162 in the NID. Sumoylation of lysine 162 increases repression by Net and
      decreases the positive activity of Net. These results increase our understanding
      of how one of the ternary complex factors regulates transcription, and contribute
      to the understanding of how different domains of a transcription factor
      participate in the complexity of regulation of gene expression.

PMID- 15580298
TI  - KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible
      mechanism underlying loss of KAI1 expression in cancer cells.
AB  - A molecular mechanism to explain reduced KAI1 expression in invasive and
      metastatic tumour cells remains elusive. In this report, we extend an earlier
      study in bladder cells to confirm that a 76 bp region of the KAI1 promoter
      (residues -922 to -847), with binding motifs for p53, AP1 and AP2, is required
      for high level activity of a KAI1 reporter in prostate cancer cell lines. Gel
      shift and supershift experiments supported binding of p53, junB and heterodimers
      of AP2alpha/AP2gamma or AP2beta/AP2gamma to this sequence. Introduction of
      mutations into specific motifs demonstrated an essential requirement for p53 and
      junB to reporter activity, and that functional synergy between these two factors
      enhanced activity. A further elevation of reporter activity required AP2. Roles
      of individual p53, junB and AP2 proteins, as well as functional synergy between
      p53 and junB, were confirmed in transfection experiments. Western blotting
      analysis showed that an absence of wild-type p53, and/or a loss of junB and AP2
      protein expression, correlated with downregulation of KAI1 mRNA levels in a
      series of prostate cancer cell lines. A loss of p53 function and/or expression of
      junB, combined with reduced expression of specific AP2 proteins may underly
      downregulated KAI1 expression in tumour cells.

PMID- 15580299
TI  - Chemosensitization by erythropoietin through inhibition of the NF-kappaB rescue
      pathway.
AB  - Two cell lines that exemplify erythropoietin (EPO) receptor-positive tumors,
      human renal carcinoma cell lines RCC and the myelomonocytic leukemia cell line
      U937, were investigated for the apoptosis-modulatory potential of EPO. Cells
      cultured in the presence of EPO exhibited an elevated apoptotic response to
      cancer chemotherapeutic agents such as daunorubicin (Dauno) and vinblastine
      (VBL). Chemosensitization by EPO did not involve an increase in p53 activation,
      yet correlated with enhanced Bax/Bak-dependent mitochondrial membrane
      perturbation and caspase maturation. In vitro monotherapy with Dauno or VBL
      induced the degradation of IkappaBalpha, provoked the translocation of NF-kappaB
      p65/50 to the nucleus and stimulated the expression of an NF-kappaB-activatable
      reporter gene. All these signs of NF-kappaB activation were perturbed in the
      presence of EPO. Inhibition of JAK2, one of the receptor-proximal elements of EPO
      mediated signal transduction, greatly diminished the EPO-mediated
      chemosensitization and NF-kappaB inhibition. EPO lost its death-facilitating
      effects in the presence of an NF-kappaB inhibitor, underscoring the cause-effect
      relationship between EPO-mediated chemosensitization and NF-kappaB inhibition.
      Altogether, these results suggest that, at least in a specific subset of tumors,
      EPO receptor agonists can prevent activation of the NF-kappaB pathway, thereby
      enhancing the propensity of EPO receptor-positive tumor cells to undergo
      apoptosis.

PMID- 15580300
TI  - Interferons alpha and gamma induce p53-dependent and p53-independent apoptosis,
      respectively.
AB  - Type I interferon (IFN) enhances the transcription of the tumor suppressor gene
      p53. To elucidate the molecular mechanism mediating IFN-induced apoptosis, we
      analysed programmed cell death in response to type I (IFNalpha) or type II
      (IFNgamma) treatment in relation to p53 status. In two cell lines (MCF-7, SKNSH),
      IFNalpha, but not IFNgamma, enhanced apoptosis in a p53-dependent manner.
      Furthermore, only IFNalpha upregulated p53 as well as p53 target genes (Noxa,
      Mdm2 and CD95). The apoptotic response to IFNalpha decreased in the presence of
      ZB4, an anti-CD95 antibody, suggesting that CD95 is involved in this process.
      When p53 was inactivated by the E6 viral protein or the expression of a p53
      mutant, IFNalpha-induced apoptosis and p53 target genes upregulation were
      abrogated. Altogether these results demonstrate that p53 plays a pivotal role in
      the IFNalpha-induced apoptotic response. IFNalpha-induced PML was unable to
      recruit p53 into nuclear bodies and its downregulation by siRNA did not alter
      CD95 expression. In contrast, IFNgamma-induced apoptosis is p53-independent. CD95
      and IFN-regulatory factor 1 (IRF1) are directly upregulated by this cytokine.
      Apoptotic response to IFNgamma is decreased in the presence of ZB4 and strongly
      diminished by IRF1 siRNA, implicating both CD95 and IRF1 in IFNgamma-induced
      apoptotic response. Taken together, these results show that in two different cell
      lines, IFNalpha and IFNgamma, induce p53-dependent -independent apoptosis,
      respectively.

PMID- 15580301
TI  - HOXB4 confers a constant rate of in vitro proliferation to transduced bone marrow
      cells.
AB  - HOXB4 overexpression mediates increased self-renewal of haematopoietic stem cells
      (HSCs) ex vivo. Since HOXB4-expanded HSCs retain normal differentiation potential
      and there is no leukaemia development from transduced HSCs, HOXB4 represents a
      promising tool for human HSC therapy. However, the increased proliferation
      capacity of HOXB4 overexpressing fibroblasts resulting from upregulation of JunB,
      Fra-1 and cyclin D1 protein levels may indicate a potential risk associated with
      the HOXB4 overexpression approach. This prompted us to investigate the
      proliferation rate, differentiation and expression of cell cycle regulators
      directly in bone marrow cultures overexpressing HOXB4. Here we show that in
      comparison to neo-transduced control bone marrow cultures, HOXB4-overexpressing
      cultures had a more homogenous morphology and increased numbers of haematopoietic
      progenitor cells capable to generate primitive colonies in vitro. In contrast,
      neo-transduced bone marrow cells in long-term cultures showed hallmarks of
      myeloid differentiation and a reduced secondary colony forming activity. We
      further show that multilineage repopulating activity in vivo, which was present
      only in HOXB4 long-term cultures, declined over time. HOXB4 overexpression in
      vitro did not result in an increase but in a stabilization of the proliferation
      rate (1.4-1.8 cell divisions per day), while the proliferation rate of control
      neo-transduced bone marrow cultures gradually declined. Correspondingly,
      increased HOXB4 expression was paralleled by decreased expression levels of
      cyclins, CDKs and AP-1 family members. These results suggest that the growth rate
      of HOXB4- compared to neo-transduced bone marrow cells remains constant in long
      term cultures along with a suppression of myeloid differentiation. In contrast to
      HOXB4 overexpression in fibroblasts, bone marrow cells engineered to overexpress
      HOXB4 do not upregulate AP-1 complex members or cyclins indicating that HOXB4
      acts in a cell type-specific way.

PMID- 15580302
TI  - Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis.
AB  - The tumor suppressor protein p53 regulates transcription of many genes that
      mediate cell cycle arrest, apoptosis, DNA repair and other cellular responses.
      Here we show that Ipaf, a human CED-4 homologue and an activator of caspase-1, is
      induced by p53. Overexpression of p53 by transfection in U2OS and A549 cells
      increased Ipaf mRNA levels. Treatment of p53-positive cell lines U2OS and MCF-7
      with the DNA damaging drug, doxorubicin, which increases p53 protein level,
      induced expression of Ipaf mRNA but similar treatment of MCF-7-mp53 (a clone of
      MCF-7 cells expressing mutant p53) and p53-negative K562 cells showed much less
      induction of Ipaf gene expression. Expression analysis for Ipaf mRNA in
      doxorubicin-treated human tumor cell lines suggests that p53-dependent as well as
      p53-independent mechanisms are involved in the regulation of Ipaf gene expression
      in a cell-type-specific manner. The Ipaf promoter was activated by normal p53 but
      not by His(273) mutant of p53. A functional p53-binding site was identified in
      the Ipaf promoter. A dominant-negative mutant of Ipaf inhibited p53-induced and
      doxorubicin-induced apoptosis by about 50%. Ipaf-directed small hairpin RNA
      downregulated p53-induced Ipaf gene expression and also reduced p53-induced
      apoptosis. Doxorubicin-induced apoptosis was also inhibited by Ipaf-directed
      small hairpin RNA. Our results show that p53 can directly induce Ipaf gene
      transcription, which contributes to p53-dependent apoptosis in at least some
      human cells.

PMID- 15580303
TI  - Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and
      sensitive to TGF-beta1 expression.
AB  - A parity-induced mammary population, marked by beta-galactosidase expression
      conditionally activated through cre-lox recombinase originates in WAP-Cre/Rosa
      lox-STOP-lox-LacZ (WAP-Cre/Rosa-LacZ) female mice during pregnancy, lactation and
      involution. During subsequent pregnancies, these parity-induced mammary
      epithelial cells (PI-MEC) proliferated to produce new secretory acini composed of
      secretory luminal cells and myoepithelium. In serial transplantation assays, PI
      MEC were able to self-renew over several transplant generations and to contribute
      significantly to the resulting mammary outgrowths. In limiting dilution
      transplantation, they proliferated to produce both luminal and myoepithelial
      cells, comprised both lobule-limited and duct-limited epithelial outgrowths, and
      differentiated into all the cellular subtypes recognized in murine mammary
      epithelium. TGF-beta1 expression from the whey acidic protein promoter (WAP) in
      triply transgenic females did not prevent the appearance of PI-MEC after
      pregnancy despite the absence of full lactation or their ability to proliferate
      and produce progeny with diverse cellular fates in situ upon subsequent
      pregnancies. However, in transplants from triple transgenic parous females, the
      WAP-TGF-beta1-positive PI-MEC did not contribute to the newly recapitulated
      mammary outgrowths, suggesting that they were incapable of expansive cellular
      proliferation (self-renewal). This result is consistent with our earlier
      publication that WAP-TGF-beta1 expression in mammary epithelium induces premature
      stem cell senescence in mammary transplants and decreases mammary cancer risk in
      mouse mammary tumor virus (MMTV)-infected females even after multiple
      pregnancies.

PMID- 15580304
TI  - Selectively frequent expression of CXCR5 enhances resistance to apoptosis in
      CD8(+)CD34(+) T cells from patients with T-cell-lineage acute lymphocytic
      leukemia.
AB  - We investigated CD4(+)CD34(+), CD8(+)CD34(+), CD4(+)CD34(-), and CD8(+)CD34(-) T
      cells from cord blood and from typical patients with T-cell-lineage acute
      lymphocytic leukemia and T-cell-lineage chronic lymphocytic leukemia in terms of
      expression and functions of CXCR5/CXCL13. We found that CXCR5 was selectively
      frequently expressed on T-cell-lineage acute (chronic) lymphocytic leukemia (T
      ALL) CD8(+)CD34(+) T cells, but not on T-ALL CD4(+)CD34(+), CD4(+)CD34(-), and
      CD8(+)CD34(-) T cells. CXCR5 was rarely expressed on all types of CD34(+) and
      CD34(-) CB or T-CLL T cells. CXCL13/B cells attracting chemokine 1 induced
      significant resistance to TNF-alpha-mediated apoptosis in T-ALL CD8(+)CD34(+) T
      cells, instead of induction of chemotactic and adhesive responsiveness. A
      proliferation-inducing ligand expression in T-ALL CD8(+)CD34(+) T cells was
      upregulated by CXCL13/BCA-1 (B-cell attracting chemokine 1). The CXCR5/CXCL13
      pair by means of activation of APRIL (A proliferation-inducing ligand) induced
      resistance to apoptosis in T-ALL CD8(+)CD34(+) T cells in livin-dependent manner.
      In this process, cell-cell contact in culture was necessary. Based on our
      findings, we suggested that there were differential functions of CXCR5/CXCL13 in
      distinct types of cells. Normal lymphocytes, especially naive B and T cells,
      utilized CXCR5/CXCL13 for migration, homing, maturation, and cell homeostasis, as
      well as secondary lymphoid tissue organogenesis. Meanwhile, certain malignant
      cells took advantages of CXCR5/CXCL13 for infiltration, resistance to apoptosis,
      and inappropriate proliferation.

PMID- 15580305
TI  - Induction of reactive oxygen species renders mutant and wild-type K-ras
      pancreatic carcinoma cells susceptible to Ad.mda-7-induced apoptosis.
AB  - Pancreatic cancer is exceptionally aggressive with no long-term effective
      therapy. Current interventional approaches, including surgery, radiation and/or
      chemotherapy, have done little to quell the mortality associated with this
      malignancy. Subtraction hybridization identified a cancer-specific apoptosis
      inducing cytokine gene, melanoma differentiation associated gene-7/interleukin-24
      (mda-7/IL-24), with a broad range of selective antitumor activity in diverse
      cancers both in vitro and in vivo in nude mice and recently in patients with
      advanced carcinomas and melanomas. Unlike most neoplasms, pancreatic cancers
      display innate resistance to mda-7/IL-24-induced apoptosis, which correlates with
      a diminished capacity to convert mda-7/IL-24 mRNA into protein. We presently
      demonstrate that this translational block can be reversed by treatment with
      agents that elevate reactive oxygen species (ROS). Induction of apoptosis in
      vitro and suppression of tumorigenesis in vivo in nude mice are induced in
      pancreatic cancers, irrespective of the status of their K-ras gene, only when
      tumor cells simultaneously express mda-7/IL-24 and are treated with a ROS
      inducer, such as arsenic trioxide (ARS), N-(4-hydroxyphenyl) retinamide (HPR) or
      dithiophene (NSC656240 (NSC)). In pancreatic cancer cells constitutively
      expressing mda-7/IL-24 mRNA, a single treatment with arsenic trioxide, HPR or
      NSC656240 induces apoptosis, which correlates with production of MDA-7/IL-24
      protein. The specificity of this action is documented by the ability of ROS
      inhibitors, including N-acetyl-L-cysteine and Tiron, to block this killing
      effect. Of potential clinical significance, similar treatment of normal cells
      does not elicit significant changes in growth nor does it induce apoptosis.
      Analysis of signal transduction changes in pancreatic carcinoma cells infected
      with Ad.mda-7 in combination with a ROS-inducer indicate that cell death
      correlates with modulation of discrete cassettes of multiple signaling pathways
      in a pancreatic cancer cell-specific manner, supporting global signaling
      dysregulation as a potential mediator of apoptosis induction. These findings
      suggest a promising combinatorial approach for safely promoting cell death in
      pancreatic tumors that provides a rational framework for developing a selective
      and effective therapy for this invariably fatal cancer.

PMID- 15580306
TI  - Tumor suppressive role of a 2.4 Mb 9q33-q34 critical region and DEC1 in
      esophageal squamous cell carcinoma.
AB  - The key genes involved in the development of esophageal squamous cell carcinoma
      (ESCC) remain to be elucidated. Previous studies indicate extensive genomic
      alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer
      approach, this study provides functional evidence and narrows down the critical
      region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb
      region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a
      high prevalence of allelic loss in this CR is also observed in primary ESCC
      tumors by microsatellite typing. Allelic loss is found in 30/34 (88%) tumors and
      the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low
      expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in
      esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably
      expressing DEC1 transfectants provide functional evidence for inhibition of tumor
      growth in nude mice and DEC1 expression is decreased in tumor segregants arising
      after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC
      primary tumors. This study provides the first functional evidence for the
      presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate
      TSG that may be involved in ESCC development.

PMID- 15580307
TI  - Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological marker of
      colon neoplasia.
AB  - Cancers of the colon and rectum are the second leading cause of cancer death
      among adult Americans. When detected at early stages, colon cancer is highly
      curable. Colonoscopy, an effective but invasive screening test, has been limited
      in its public acceptance. The goal of this study was to identify novel serum
      markers of colon cancers and precancerous colon adenomas as potential candidates
      for noninvasive detection of early colon neoplasms. Employing expression
      microarrays, we identified colon cancer secreted protein-2 (CCSP-2) as a novel
      transcript whose expression is generally absent in normal colon and other normal
      body tissues, but that is induced an average of 78-fold in Stage II, III, and IV
      colon cancers, as well as in colon adenomas and colon cancer cell lines. These
      findings were validated by real-time PCR analysis in an independent panel of
      colon cancer cases. Moreover, CCSP-2 was shown to encode a secreted protein that
      circulates stably and is detectable in the blood of mice bearing human cancer
      xenografts transfected with epitope-tagged CCSP-2. As a novel secreted protein
      that is markedly induced in colon adenomas and cancers, CCSP-2 is a novel
      candidate for development as a diagnostic serum marker of early stage colon
      cancer.

PMID- 15580308
TI  - Restoring mismatch repair does not stop the formation of reciprocal
      translocations in the colon cancer cell line HCA7 but further destabilizes
      chromosome number.
AB  - An important anticarcinogenic function of the mismatch repair (MMR) system is its
      role in preventing recombination between similar, but nonidentical (homeologous)
      sequences, thus preventing chromosomal rearrangements. We recently identified a
      novel chromosomal instability (CIN) phenotype in an MMR defective colon cancer
      cell line (HCA7) characterized by an ongoing tendency to multiple reciprocal
      chromosomal translocations. To analyse the relation between MMR and chromosomal
      changes more closely, the HCA7 stem clone was divided into three stocks. The
      first was stably transfected with MLH1 expression plasmid, the second was
      regularly exposed to the demethylating agent 5-azacytidin to re-express the
      hypermethylated MLH1 gene, and the third was an unmanipulated control stock. All
      stocks were propagated in vitro for 55-80 passages and, furthermore, some of the
      early passages were irradiated to induce DNA double-strand breaks. Multiplex
      fluorescent in situ hybridization (M-FISH) analysis showed that all three stocks
      acquired varying numbers of reciprocal translocations and other structural
      changes at some point. Interestingly, the control stock, which is MMR defective,
      maintained its numerical chromosomal stability, while some of the MMR-proficient
      clones showed additional numerical instability. Although the control stock was
      less sensitive to irradiation, its surviving clones showed marked stability of
      chromosome structure and number compared to the MMR-competent stocks. These
      results show that restoring MMR does not prevent the development of reciprocal
      translocations but rather predisposes cells to numerical CIN after irradiation.
      Thus, the accumulating data suggest that MMR defect may not be necessary for the
      development of reciprocal chromosomal translocations but might be permissive.

PMID- 15580310
TI  - 17beta-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro:
      potential role in cancerous progression of breast and prostate to a premetastatic
      state in vivo.
AB  - Human WWOX gene encodes a proapoptotic WW domain-containing oxidoreductase WOX1
      (also named WWOX, FOR2 or WWOXv1). Apoptotic and stress stimuli activate WOX1 via
      Tyr33 phosphorylation and nuclear translocation. WOX1 possesses a tetrad NSYK
      motif in the C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain,
      which may bind estrogen and androgen. Here, we determined that 17beta-estradiol
      (E(2)) activated WOX1, p53 and ERK in COS7 fibroblasts, primary lung epithelial
      cells, and androgen receptor (AR)-negative prostate DU145 cells, but not in
      estrogen receptor (ER)-positive breast MCF7 cells. Androgen also activated WOX1
      in the AR-negative DU145 cells. These observations suggest that sex hormone
      mediated Tyr33 phosphorylation and nuclear translocation of WOX1 is independent
      of ER and AR. Stress stimuli increase physical binding of p53 with WOX1 in vivo.
      We determined here that E(2) increased the formation of p53/WOX1 complex and
      their nuclear translocation in COS7 cells; however, nuclear translocation of this
      complex could not occur in MCF7 cells. By immunohistochemistry, we determined
      that progression of prostate from normal to hyperplasia, cancerous and metastatic
      stages positively correlate with upregulation and activation of WOX1 and WOX2
      (FOR1/WWOXv2). In contrast, breast cancer development to a premetastatic state is
      associated with upregulation and Tyr33 phosphorylation of cytosolic WOX1 and
      WOX2, followed by significant downregulation or absent expression during
      metastasis. These Tyr33-phosphorylated proteins are mostly located in the
      mitochondria without translocating to the nuclei, which is comparable to those
      findings in cultured breast cancer cells. Together, sex steroid hormone-induced
      activation of WOX1 and WOX2 is independent of ER and AR, and this activation
      positively correlates with cancerous progression of prostate and breast to a
      premetastatic state.

PMID- 15580309
TI  - Combined treatment with EGFR inhibitors and arsenite upregulated apoptosis in
      human EGFR-positive melanomas: a role of suppression of the PI3K-AKT pathway.
AB  - Epidermal growth factor receptor (EGFR) is expressed, albeit at low or
      intermediate levels, in human melanomas at the different stages of tumor
      progression. Coexpression of EGFR with its ligand TGFalpha indicates their role
      in paracrine and autocrine growth regulation of melanomas. As it was previously
      observed for several types of cancer, specific inhibitors of EGFR-mediated
      signaling may reduce antiapoptotic properties of cancer cells and sensitize them
      to cytotoxic drugs. We recently reported that arsenite, particularly in
      combination with inhibitors of the PI3K-AKT and mitogen-activated protein kinase
      (MAPK) kinase (MEK)-extracellular signal-regulated kinase (ERK) pathways, induces
      high levels of apoptosis in different melanomas. Since EGFR signaling operates
      via activation of the PI3K-AKT and MEK-ERK pathways, we suggested that the
      combination of arsenite and EGFR inhibitors might also effectively induce
      apoptosis in melanoma. Here, we demonstrate that a moderate concentration of
      arsenite (5-10 muM) indeed upregulates apoptosis induced by EGFR inhibitors in
      EGFR-positive melanomas. In contrast, induction of apoptosis in melanomas with
      negligible surface expression of EGFR or with defective EGFR signaling requires
      direct suppression of the PI3K-AKT and MAPK pathways by specific pharmacological
      inhibitors in the presence of arsenite. Under these conditions, metastatic
      melanoma cell lines undergo TNF-related apoptosis-inducing ligand (TRAIL)- and
      tumor necrosis factor alpha (TNFalpha)-mediated apoptosis. Taken together, these
      data provide additional approaches in sensitizing melanomas to the cytotoxic
      effects of specific inhibitors of survival pathways.

PMID- 15580311
TI  - The HTLV-I Tax oncoprotein targets the retinoblastoma protein for proteasomal
      degradation.
AB  - Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell
      leukemia (ATL), is estimated to affect 10-20 million people worldwide. The
      transforming ability of HTLV-I has been largely attributed to the viral protein
      Tax, which modulates the activity of several well-known cell cycle regulators. An
      important cell cycle regulator, the retinoblastoma (Rb) protein, is often
      inactivated in many cancers including virally induced cancers. Upon examination
      of Rb status, we observed a decrease in Rb protein expression in HTLV-1-infected
      cell lines as well as in ex vivo ATL patient samples. Transient transfection
      assays indicated that decreased Rb protein levels were Tax dependent. Here, we
      demonstrate for the first time that Tax directly associates with Rb. This
      interaction was localized within the B pocket of Rb and the C-terminus of Tax (aa
      245-353). Within the C-terminus of Tax, we have identified an LXCXE-like motif,
      that when mutated resulted in the loss of Tax/Rb interaction. Furthermore,
      through the use of proteasome inhibitors, such as MG-132, in vivo and proteasome
      degradation assays in vitro, we found that Tax destabilizes the hypo
      phosphorylated (active) form of Rb via the proteasome pathway. Therefore, we
      propose a model whereby Tax targets Rb to the proteasome by acting as a molecular
      bridge bringing Rb into contact with the proteasome for degradation.

PMID- 15580312
TI  - Alternative phospholipase D/mTOR survival signal in human breast cancer cells.
AB  - Cancer cells generate survival signals to suppress default apoptotic programs
      that protect from cancer. Phosphatidylinositol-3-kinase (PI3K) generates a
      survival signal that is frequently dysregulated in human cancers. Phospholipase D
      (PLD) has also been implicated in signals that promote survival. One of the
      targets of PLD signaling is mTOR (mammalian target of rapamycin), a critical
      regulator of cell cycle progression and cell growth. We report here that elevated
      PLD activity in the MDA-MB-231 human breast cancer cell line generates an mTOR
      dependent survival signal that is independent of PI3K. In contrast, MDA-MB-435S
      breast cancer cells, which have very low levels of PLD activity, are dependent on
      PI3K for survival signals. The data presented here identify an alternative
      survival signal that is dependent on PLD and mTOR and is active in a breast
      cancer cell line where the PI3K survival pathway is not active.

PMID- 15580313
TI  - High activin A-expression in human neuroblastoma: suppression of malignant
      potential and correlation with favourable clinical outcome.
AB  - Amplification of the MYCN oncogene contributes to the malignant progression of
      human neuroblastomas, but the mechanisms have remained unclear. We have
      previously demonstrated that N-Myc facilitates angiogenesis by downregulating an
      angiogenesis inhibitor identified as the inhibin betaA homodimer activin A. Here,
      we have sought to define the molecular, biological and clinical consequences of
      activin A expression in human neuroblastoma. We report that enhanced activin A
      expression suppresses proliferation and colony formation of human neuroblastoma
      cells with amplified MYCN in vitro; that it inhibits neuroblastoma growth and
      angiogenesis in vivo; that it is highly expressed in differentiated, but not
      undifferentiated human neuroblastomas; and that it correlates with favourable
      outcome of neuroblastoma patients. Our results indicate that high activin A
      expression plays an important beneficial role in human neuroblastoma.

PMID- 15580314
TI  - Differential methylation of genes that regulate cytokine signaling in lymphoid
      and hematopoietic tumors.
AB  - The perturbations of the cytokine signaling pathway play an important role in
      lymphoid/hematopoietic tumors. Aberrant promoter methylation is the major
      mechanism of gene silencing in tumors. We examined 150 lymphoid/hematopoietic
      tumors or potential premalignant specimens, 55 control specimens and 12 EBV
      transformed B lymphoblastoid cultures and 10 lymphoma/leukemia (L/L) or multiple
      myeloma (MM) cell lines for the methylation (and, in cell lines, of the
      expression status) of three genes involved in the cytokine signaling pathway. The
      genes were: SHP1, a protein tyrosine phosphatase; SYK, a protein kinase; and
      SOCS1, a suppressor of cytokine signaling. Our major findings were: (1) one or
      more of the three genes was frequently methylated in L/L and MM cell lines and
      there was good concordance (90-100%) between methylation and loss of gene
      expression; (2) treatment of L/L cell lines with a demethylating agent resulted
      in re-expression of SHP1 protein and downregulation of phosphorylated STAT3 in
      L/L cell lines; (3) all 55 control specimens and the lymphoblastoid cultures were
      negative for methylation of the three genes; (4) non-Hodgkin's lymphomas (100%),
      and leukemias (94%) had almost universal methylation of SHP1 and relatively less
      frequent (<30%) methylation of SOCS1 and SYK; (5) MM and monoclonal gammopathy of
      unknown significance (MGUS) had infrequent methylation of SHP1 (<20%), and
      occasional methylation of SOCS1 and SYK; and (6) comparable methylation
      frequencies for SOCS1 were observed in MM and MGUS, suggesting that SOCS1
      methylation is an early event in MM pathogenesis. At least one gene was
      methylated in 119 of 130 (93%) of the malignant and 12 of 20 (60%) of the MGUS
      samples. Our findings demonstrate that the perturbations of cytokine signaling
      via silencing of these three genes are almost universal in lymphoid/hematopoietic
      tumors but the patterns of gene methylated for L/L and plasma cell dyscrasias are
      different.

PMID- 15580315
TI  - [III Guidelines on the treatment of myocardial acute infarction].

PMID- 15580316
TI  - A comparative study of skills in virtual laparoscopy and endoscopy.
AB  - BACKGROUND: The present study was designed to investigate whether there is a
      correlation between manual skills in laparoscopic procedures and manual skills in
      flexible endoscopy. METHODS: In a prospective study using laparoscopy and
      endoscopy simulators (MIST-VR, and GI-Mentor II), 24 consecutive subjects
      (gastrointestinal surgeons, novice and experienced gastroenterologists, and
      untrained subjects) were asked to perform laparoscopic and endoscopic tasks.
      Their performance was assessed by the simulators' software and by observers
      blinded to the levels of subjects' experience. Performance in experienced vs
      inexperienced subjects was compared. Score pairs of three parameters--time,
      errors, and economy of movement--were also compared. RESULTS: Experienced
      subjects performed significantly better than inexperienced subjects on both tasks
      in terms of time, errors, and economy of movement (p < 0.05). All three
      performance parameters in laparoscopy and endoscopy correlated significantly (p <
      0.02). CONCLUSION: Both simulators can distinguish between experienced and
      inexperienced subjects. Observed skills in simulated laparoscopy correlate with
      skills in simulated flexible endoscopy. This finding may have an impact on the
      design of training programs involving both procedures.

PMID- 15580317
TI  - [Eptifibatide and percutaneous coronary intervention].

PMID- 15580318
TI  - [Eptifibatide in patients with percutaneous coronary intervention in clinical
      practice. Results of a prospective registry].
AB  - BACKGROUND AND PURPOSE: The use of potent platelet inhibitors has been shown to
      reduce the rate of ischemic complications in patients with percutaneous coronary
      intervention (PCI) in randomized clinical trials. Eptifibatide is a small
      molecule glycoprotein (GP) IIb/IIIa receptor inhibitor. Eptifibatide given with a
      double bolus of 180 microg/kg 10 min apart followed by an infusion of 2.0
      microg/kg/h achieves a high grade of platelet inhibition, which was associated
      with a highly significant clinical benefit in the randomized ESPRIT Study. The
      aim of the present prospective registry was to evaluate the efficacy and safety
      of eptifibatide in clinical practice. METHODS: A total of 673 patients who
      received eptifibatide during PCI were prospectively enrolled in the registry
      between January 2001 and November 2002 in 31 clinical centers. RESULTS: The
      intervention was performed for stable angina in 283 patients (42.1%), for
      unstable angina in 70 patients (10.4%), for non-ST elevation myocardial
      infarction in 120 patients (17.8%), and for acute ST elevation myocardial
      infarction in 200 patients (29.7%). Therapy with eptifibatide was predominantly
      initiated in the catheter laboratory before or during the intervention and
      maintained for a mean of 20 h. Major bleeding complications, in 50% of the
      patients at the catheter insertion site, were observed in 1.2% of the patients. A
      thrombocytopenia < 100,000/microl was not reported. The total mortality rate was
      < 1%, a myocardial infarction or reinfarction was observed in up to 3%, depending
      on the clinical indication for PCI. CONCLUSION: These data are comparable to the
      results reported in randomized clinical trials with eptifibatide and document the
      safety and efficacy of this small-molecule GP IIb/IIIa inhibitor in clinical
      practice in a wide range of patients undergoing PCI.

PMID- 15580319
TI  - Diagnosis of perioperative myocardial infarction after coronary artery bypass
      surgery.

PMID- 15580320
TI  - Comparison of cardiac troponin I versus T and creatine kinase MB after coronary
      artery bypass grafting in patients with and without perioperative myocardial
      infarction.
AB  - BACKGROUND AND PURPOSE: Cardiac troponins have shown to be specific markers of
      myocardial injury. The aim of this prospective study was to compare patterns and
      kinetics of troponin I and T after coronary artery bypass grafting (CABG) with or
      without perioperative myocardial infarction (PMI). PATIENTS AND METHODS: 119
      patients (male/female: 96/23, age 64 +/- 10 years) underwent first time elective
      CABG. Preoperative mean ejection fraction was 55.8% +/- 15.6%. The mean number of
      grafts was 3.1 +/- 1.1/patient, in 85.7% the internal mammary artery was used.
      Cardiac troponin I (cTnI) and T (cTnT) levels, total serum activities of creatine
      kinase (CK) and creatine kinase isoenzyme MB (CK-MB) were measured before
      operation, at arrival on the intensive care unit (ICU), and 6, 12, 24, 48, and
      120 h after unclamping of the aorta. Twelve lead electrocardiograms (ECGs) were
      recorded preoperatively and at days 1, 2, and 5. Perioperative data and
      postoperative cTnI and cTnT levels were correlated statistically. RESULTS: Two
      patients died due to refractory myocardial failure in the early postoperative
      period. For further evaluation, patients were divided in two groups according to
      postoperative ECG changes (group I: patients without PMI, n = 107; group II:
      patients with PMI, n = 10: six of them with Q-wave and four of them with non-Q
      wave PMI). Calculated best cutoff values for cTnI and cTnT were 8.35 microg/l and
      0.768 microg/l in ROC (receiver-operator characteristic) analysis. Serum
      concentrations of cTnI, and cTnT were in the normal range preoperatively and
      increased significantly after surgery in both groups. In both groups, cTnI
      reached its medium peak level after 24 h (group I: 2.7 microg/l, 95% confidence
      interval [CI]: [2.1,3.2]); group II: 70.5 microg/l). CTnT reached its medium peak
      level in group I without PMI after 48 h (0.298 microg/l, 95% CI: [0.254,0.354]),
      in group II with PMI not until 120 h (3.0 microg/l) postoperatively. In group II
      serum level of both troponins remained considerably high at 120 h (cTnI median =
      10.75 microg/l, cTnT median = 3 microg/l). CONCLUSION: Release patterns of cTnI
      and cTnT after CABG are different: cTnI reaches its postoperative peak value
      earlier and declines more quickly than cTnT. After uncomplicated CABG, serum
      levels of both cardiac troponins remain continuously low. Elevated concentrations
      reflect perioperative myocardial ischemia or infarction. CTnT shows a different
      release pattern in patients with or without myocardial infarction.

PMID- 15580321
TI  - European survey on circadian variation of angina pectoris (ESCVA) in treated
      patients.
AB  - BACKGROUND AND PURPOSE: Previous reports of a circadian variation of angina
      pectoris were based primarily on selected patients of clinical studies. The
      present ESCVA Study (European Survey on Circadian Variation of Angina Pectoris)
      was designed to determine the timing of angina pectoris attacks in outpatients,
      the association of wake time and possible external triggers with angina attacks,
      and the influence of cardiac medication on the circadian pattern. PATIENTS AND
      METHODS: Inclusion criteria were stable angina pectoris for at least 3 months,
      average frequency of two or more attacks per week, and treatment with on-demand
      nitrates. Standardized self-administered questionnaires were provided to all
      participating physicians to obtain medical information and to their patients to
      obtain prospective recordings of angina attacks during the 7 subsequent days.
      RESULTS: From January 1998 to March 1999, 1,333 patients (60% male, 65 +/- 10
      years, 40% female, 68 +/- 10 years) were enrolled in 243 centers of six European
      countries and reported a total of 4,293 angina pectoris attacks (range 0-48 per
      patient). The occurrence of angina pectoris demonstrated a significant circadian
      variation (p < 0.001) with a primary morning peak from 09:00 to 12:00 o'clock
      (relative risk 2.9, 95% confidence interval 2.6-3.2, compared to other times of
      day) and a secondary afternoon peak from 15:00 to 18:00 o'clock (relative risk
      1.5, 95% confidence interval 1.3-1.7). Of all angina attacks 50% occurred within
      the initial 6 h after awakening, and 74% were associated with possible external
      triggers such as physical activity or anger. CONCLUSION: The study demonstrated a
      marked wake time-related circadian variation in the occurrence of angina pectoris
      attacks. To improve preventive strategies, type, dosage and particularly timing
      of cardiac medication appear of importance, as may be behavior modification.

PMID- 15580322
TI  - Risk stratification by the "EPA+DHA level" and the "EPA/AA ratio" focus on anti
      inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty acids.
AB  - The identification of risks associated with sudden cardiac death requires further
      investigations. The question was addressed whether parameters can be established
      which not only describe an increased risk for an enhanced electrical instability
      of the heart but also of inflammatory events underlying plaque rupture. Emphasis
      is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of
      EPA and DHA are required for most of their biological effects, it appears
      essential not only to build up stores in the body for release of these fatty
      acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl
      esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters
      are taken up more slowly within 24 h. For the administration of 1 g/day highly
      purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that
      EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from
      2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10
      days. A gas chromatographic procedure was established which requires only 10
      microl of whole blood for the identification of more than 35 fatty acids.
      Evidence is summarized strengthening the concept that a low "EPA+DHA level"
      presents a risk for sudden cardiac death and that the administration of 840
      mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6%
      that is associated with a marked protection from sudden cardiac death. For
      reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is
      required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl
      esters. For assessing influences from pro-inflammatory eicosanoids and cytokines,
      the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic
      parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in
      fish dishes of the cafeteria of the Philipps University Hospital Marburg,
      Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100
      g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA
      administered in the GISSI Prevention Study in the form of ethyl ester which
      markedly reduced the risk of sudden cardiac death in postmyocardial infarction
      patients. Nonetheless, at least two preferably oily fish meals per week should be
      consumed as preventive measure by persons without coronary artery disease. With
      documented coronary heart disease, it was advised to consume approximately 1
      g/day of EPA+DHA.

PMID- 15580323
TI  - [Atrial isomerism and visceral heterotaxy].
AB  - Atrial isomerism and visceral heterotaxy describe complex pathoanatomic findings
      with defects in the determination of lateralization. Differentiation of right and
      left atrial isomerism was based on the anatomy of the atrial appendages and
      bronchial tree and often associated with asplenia in right atrial isomerism and
      polysplenia in left atrial isomerism. In these pa tients complex cardiac
      anomalies determine clinical symptoms and diagnostic procedures. At primary
      diagnosis in the neonatal period, systemic venous and pulmonary venous
      connections and intracardiac anatomy are identified using the sequential
      segmental approach. Therapeutic decisions and palliative procedures can usually
      be based on these initial echocardiographic findings. As many of the patients
      were found to have a functionally univentricular heart, surgical procedures
      following the Fontan principle (lateral tunnel or extracardiac conduit procedure)
      were introduced in patients with heterotaxy syndrome and successfully performed.
      Early survival and long-term outcome vary depending on associated cardiac and
      systemic and pulmonary venous anomalies. The therapeutic options and mid-term
      results in patients with heterotaxy syndrome undergoing the Fontan procedure are
      reported.

PMID- 15580324
TI  - [Heart transplantation and assist devices].
AB  - BACKGROUND: Although drug therapy of patients with chronic heart failure has
      improved significantly over the years, mortality still remains high. At present,
      heart transplantation is the gold standard therapy for patients with end stage
      heart disease. Due to the limited number of organs, a growing number of patients
      require the implantation of mechanical assist devices. HEART TRANSPLANTATION:
      Because of the excellent long-term survival after cardiac transplantation,
      current studies focus on long-term complications. The aim of these studies is the
      establishment of an immunosuppressive strategy that effectively prevents cardiac
      allograft vasculopathy in combination with a low incidence of negative side
      effects. Furthermore, quality of life is a major focus of current interest.
      ASSIST DEVICES: Assist device implantation has changed from an experimental to a
      routine procedure in several centers. Still, many problems have to be solved.
      Especially because of recurrent infections the long-time use of assist devices is
      limited. For final judgment, results of current studies have to be awaited.

PMID- 15580325
TI  - The challenge presented by right atrial myxoma.
AB  - BACKGROUND AND PURPOSE: Right atrial myxoma can be heralded by nonspecific
      constitutional symptoms-i. e., remittent or lasting fever; weight loss; chronic
      anemia and general arthralgia-and may escape timely diagnosis until severe
      complications develop: i. e., pulmonary hypertension due to embolism from
      fragments originating from the tumor mass, or, by blocking the right
      atrioventricular ostium, a Budd-Chiari syndrome with acute abdominal pain.
      Myocardial tamponade and infected right atrial myxomas are reported
      casuistically. META-ANALYSIS: This study, covering 1,029 patients from 32
      reports, represents the most extensive meta-analysis to date of recent
      publications on patients with intracardiac myxomas who had undergone surgery
      followed by histological confirmation. 83.0% of myxomas studied were located in
      the left and 12.7% in the right atrial cavity. Even more rarely, the tumor was
      present in the left (0.6%) or right (1.7%) ventricles; it was biatrial in 1.3%
      and multilocular in 0.8% of cases. The age of all reported individuals varied
      between 1 month and 81 years (mean value of reported mean ages: 50 years); 65% of
      the patients were female. In a subpopulation of 154 individuals, the fraction of
      familial cardiac myxomas was 4.5%. CASE STUDY: For a 68-year-old patient with
      recurrent fever of unknown origin, weight loss, exertional dyspnea, and
      tachycardia, the authors further describe epidemiology, clinical symptoms,
      prognosis, and the specific diagnostic and therapeutic challenges involved in the
      rare case of a right sided atrial myxoma.

PMID- 15580326
TI  - Successful primary correction of tetralogy of fallot with pulmonary atresia and
      aortopulmonary window in a 2,220-g neonate with a valved bovine jugular vein
      conduit.
AB  - Prenatal diagnosis of tetralogy of Fallot with pulmonary atresia (TOF/PA) was
      confirmed in a newborn with a birth weight of 2,095 g. Additionally, an
      aortopulmonary window (APW) type I was diagnosed on echocardiography. The
      operation was performed at the age of 4 weeks due to congestive heart failure.
      The APW was closed with a pericardial patch, the ventricular septal defect (VSD)
      with a Dacron patch, and the right ventricular outflow tract (RVOT) was
      reconstructed with a 12-mm bovine jugular vein valved conduit (Contegra,
      Medtronic Inc., Minneapolis, MN, USA). At 15-month follow-up, the patient is in
      excellent clinical condition without medication. On echocardiography, the conduit
      showed a mean gradient of 11 mmHg with first-degree insufficiency.

PMID- 15580327
TI  - [Left ventricular pseudoaneurysm due to traumatic papillary muscle avulsion].

PMID- 15580328
TI  - [Distal embolization: manifestations and consequences].

PMID- 15580329
TI  - [Anastomotic leakage in the gastrointestinal tract-repair and prognosis].
AB  - Anastomotic leakage is still a serious complication in surgery, resulting in
      increased morbidity and mortality. The reasons for its onset are various and due
      to two main reasons: general risk factors of the individual patient and technical
      surgical factors influencing the outcome after gastrointestinal anastomoses.
      Changes in the extracellular matrices, particularly due to collagen metabolism,
      and related disturbances are assumed to be important factors influencing wound
      healing processes. The technique chosen and the surgical skill are important with
      regard to inflammation and tissue necroses at the anastomotic line. Analysis of
      data obtained by clinical studies that concern clinical risk factors for
      anastomotic leakage reveal an inhomogeneous picture. Attempts to develop risk
      profiles or scores based on these results have failed until now. Problems
      encompass the complexity of wound healing processes, and it is questionable
      whether our current knowledge about them is complete. Therefore, profound
      understanding of anastomotic leakage requires in-depth analysis of the
      interaction of extracellular matrix components. Preliminary results indicate the
      presence of a risk population with collagen metabolism disturbances that have a
      major effect on wound healing after gastrointestinal anastomosis.

PMID- 15580330
TI  - [Iatrogenic nerve injuries. Part 1: Frequency distribution, new aspects, and
      timing of microsurgical treatment].
AB  - OBJECTIVE: The aim of this study was to analyze the number and types of
      iatrogenic nerve injuries operated on during a 13-year period at a relatively
      busy nerve center. METHOD: Retrospective analysis was done of 191 cases
      surgically treated because of iatrogenic nerve injuries. RESULTS: Most iatrogenic
      nerve injuries occurred after surgical procedures. As a rule, symptoms and signs
      appeared immediately after the procedure. Single nerves most often involved were
      the spinal accessory nerve at the neck ( n=27), most frequently after lymph node
      biopsy, and the median nerve in the carpal tunnel ( n=25), usually after carpal
      tunnel release and most frequently after endoscopic technique. Following in
      frequency are the common peroneal nerve ( n=16), superficial sensory radial nerve
      ( n=13), genitofemoral ( n=12), and superficial peroneal and tibial nerves ( n=9
      each). Clinical improvement after neurosurgical intervention appeared in 70% of
      cases. Frequently iatrogenic nerve lesions are referred with significant delay,
      that is, not during a time interval deemed appropriate for surgical intervention.
      CONCLUSION: Iatrogenic nerve lesions must be recognized in a timely manner and
      should be operated upon as early as other traumatic nerve injuries to ensure best
      chances for successful recovery.

PMID- 15580331
TI  - [A rare cause of subacute parotitis. The pathogenetic role of crystals from an
      infarcted Whartin's tumour?].
AB  - The etiology of a subacute inflammatory swelling in the area of the right parotid
      gland in a 62-years old man could not be resolved clinically. The
      histomorphological examination of the surgical specimen showed an intraglandular
      area of predominantly chronic histiocytic inflammation with foreign body reaction
      in the intimate neighbourhood of a small, subtotally infarcted Warthin's tumour.
      Not birefringent spindle-shaped crystals could be demonstrated both within the
      parotitis or intraluminally in vital parts of the Warthin's tumour. In terms of
      the possible causes of the severe intraglandular inflammation, all arguments
      favour a primary infarction of the Warthin's tumour with the release of
      intraluminal preformed crystals which secondarily induce a massive inflammation
      with foreign body reaction, corresponding to the clinical presentation of a
      subacute parotitis.

PMID- 15580332
TI  - [Endonasal removal of a large recurrent craniopharyngioma using intraoperative
      navigation].
AB  - In recent years computer-navigation systems have been commonly used in the field
      of otorhinolaryngology. Taking its limitations and possible failures into
      account, this technology is considered reasonable and helpful in routine
      paranasal sinus surgery, particularly in revision cases and complex approaches to
      the lateral skull base. We report on a patient with a large recurrent
      craniopharyngioma, and show that the use of intraoperative navigation might even
      be necessary to accomplish the desired postoperative outcome in certain cases.
      Future developments will demonstrate whether computer assisted surgery can extend
      the indications for operative procedures in complex anatomical regions.

PMID- 15580333
TI  - Outcome of severe adult thrombotic microangiopathies in the intensive care unit.
AB  - OBJECTIVE: Thrombotic microangiopathies, namely thrombotic thrombocytopenic
      purpura and hemolytic uremic syndrome, are uncommon microvascular occlusive
      diseases. Despite the dramatic improvement in the outcome by exogenous plasma
      supply, either through plasma infusion or through plasma exchange, patients
      frequently require support in the intensive care unit. In the present study, we
      evaluated the outcome of a large cohort of patients with severe thrombotic
      microangiopathies. DESIGN: A retrospective multicenter study from January 1998 to
      June 2001. SETTING: Fourteen French university hospital medical intensive care
      units. PATIENTS: Sixty three adult patients with severe thrombotic
      microangiopathies. MEASUREMENTS AND RESULTS: Of the 63 patients, 19 had a
      clinical presentation of thrombotic thrombocytopenic purpura, 18 had hemolytic
      uremic syndrome and 26 had combined neurologic and renal failures. Infections
      were the main etiology associated with thrombotic microangiopathies. The
      mortality rate was 35%. Of the survivors, all achieved complete remission.
      Whereas neurologic failure assessed through the Glasgow coma scale was an
      independent predictor of mortality [HR=0.845 (CI 95%: 0.759-0.940), P=0.002],
      renal impairment did not appear to be an adverse prognostic factor. The use of
      plasma exchange was independently associated with survival [HR=0.269 (CI 95%:
      0.104-0.691), P=0.006]. CONCLUSIONS: Thrombotic microangiopathies with severe
      organ dysfunctions leading to hospitalization in the intensive care unit are
      associated with high mortality. Neurologic impairment appears to be the main
      adverse prognostic factor correlated to mortality, and the study confirms the
      importance of plasma exchange in the treatment of high-risk patients.

PMID- 15580334
TI  - Levosimendan in septic cardiac failure.

PMID- 15580335
TI  - Value of albumin dialysis therapy in severe liver insufficiency.
AB  - A blood purification system, molecular adsorbents re-circulating system (MARS),
      is based on the removal of both protein-bound and water-soluble substances and
      toxins in the liver. We treated a total of 88 patients within 2 years. Of these
      patients, 45 had acute liver failure (ALF), 31 had acute decompensation of
      chronic liver disease, eight had graft failure and four had miscellaneous
      conditions. Of the patients with ALF, 80% survived; in 23 patients their own
      liver recovered and 13 patients underwent successful transplantation. Only 23% of
      patients with acute-on-chronic liver failure survived. Most of them were not
      considered for transplantation due to their having liver failure from alcoholism
      and from not abstaining from drinking. MARS is a promising therapy for ALF,
      allowing the patient's own liver to recover or allowing enough time to find a
      liver graft. Best results were achieved in patients who had been intoxicated with
      a lethal dose of toxin. On the other hand, we did not observe much benefit in
      patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo
      liver transplantation.

PMID- 15580336
TI  - Gemcitabine does not prevent acute rejection of the transplanted liver in rats.
AB  - Our study was designed to determine effect of gemcitabine on acute rejection of
      liver in rats. Liver transplantation was performed in rats of the Dark Agouti
      (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to
      LEW without immunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA
      to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected
      for seven consecutive days after transplantation. On day 7, blood samples and
      liver graft tissue specimens were harvested. Group A showed severe rejection
      changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in
      group C moderate rejection changes were observed (RAI 6/9). Differences were
      significant between B vs C and A vs C groups; P<0.05. Serum creatinine and urea
      levels in the gemcitabine group were significantly lower than those in the
      cyclosporine A group. We did not confirm gemcitabine ability to prevent liver
      allograft rejection.

PMID- 15580337
TI  - A novel 2-aminophenol 1,6-dioxygenase involved in the degradation of p
      chloronitrobenzene by Comamonas strain CNB-1: purification, properties, genetic
      cloning and expression in Escherichia coli.
AB  - Comamonas strain CNB-1 was isolated from a biological reactor treating wastewater
      from a p-chloronitrobenzene production factory. Strain CNB-1 used p
      chloronitrobenzene as sole source of carbon, nitrogen, and energy. A 2
      aminophenol 1,6-dioxygenase was purified from cells of strain CNB-1. The purified
      2-aminophenol 1,6-dioxygenase had a native molecular mass of 130 kDa and was
      composed of alpha- and beta-subunits of 33 and 38 kDa, respectively. This enzyme
      is different from currently known 2-aminophenol 1,6-dioxygenases in that it: (a)
      has a higher affinity for 2-amino-5-chlorophenol (K(m)=0.77 microM) than for 2
      aminophenol (K(m)=0.89 microM) and (b) utilized protocatechuate as a substrate.
      These results suggested that 2-amino-5-chlorophenol, an intermediate during p
      chloronitrobenzene degradation, is the natural substrate for this enzyme. N
      terminal amino acids of the alpha- and beta-subunits were determined to be T-V-V
      S-A-F-L-V and M-Q-G-E-I-I-A-E, respectively. A cosmid library was constructed
      from the total DNA of strain CNB-1 and three clones (BG-1, BG-2, and CG-13) with
      2-aminophenol 1,6-dioxygenase activities were obtained. DNA sequencing of clone
      BG-2 revealed a 15-kb fragment that contained two ORFs, ORF9 and ORF10, with N
      terminal amino acid sequences identical to those of the beta- and alpha-subunits,
      respectively, from the purified 2-aminophenol 1,6-dioxygenase. The enzyme was
      actively synthesized when the genes coding for the ORF9 and ORF10 were cloned
      into Escherichia coli.

PMID- 15580338
TI  - Selective subunit antagonists suggest an inhibitory relationship between NR2B and
      NR2A-subunit containing N-methyl-D: -aspartate receptors in hippocampal slices.
AB  - Glutamate receptors responding to N-methyl-D: -aspartate (NMDA) are involved in
      neural development, excitotoxicity and neuronal plasticity. Each receptor
      includes at least two NR2 subunits. Here, we have examined the effects of
      selective antagonists of NR2A and NR2B subunits (NVP-AAM07 and Ro25-6981
      respectively) on the effects of NMDA in the CA1 field of rat hippocampal slices.
      We have observed that Ro25-6981 potentiates, rather than blocks, the effects of
      NMD on field EPSPs and paired-pulse interactions (indicators of presynaptic
      effects) and on postsynaptic depolarisation in hippocampal slices. The NR2A
      subunit antagonist NVP-AAM077 blocks the effects of NMDA alone, or after
      potentiation by Ro25-6981. The potentiation of NMDA by Ro25-6981 was not
      prevented by staurosporine (protein kinase inhibitor), okadaic acid (an inhibitor
      of serine/threonine protein phosphatases) or anisomycin (protein synthesis
      inhibitor), but was prevented by cyclosporin A, which inhibits Ca2+/calmodulin
      dependent phosphatase 2B [calcineurin]. NMDA-dependent long-term potentiation
      (LTP) induced by electrical stimulation was not prevented by Ro25-6981 but was
      prevented by selective blockade of the NR2A subunit. The results suggest that, at
      both presynaptic and postsynaptic sites in the rat hippocampus, NR2B-subunit
      containing receptors limit NMDA receptor function by inhibitory restraint over
      NR2A-subunit-containing receptors, via calcineurin activation, and that LTP
      induction critically involves primarily receptors containing the NR2A subunit.
      Endogenous factors or drugs that modify this NR2B/NR2A interaction could have a
      major influence on synaptic transmission and plasticity in the brain.

PMID- 15580340
TI  - Pupillary response induced by stereoscopic stimuli.
AB  - Besides luminance change, the pupil responds to changes in spatial pattern, color
      content and target motion. Our experimental results show that transient pupillary
      constriction can also be elicited by dichoptically viewing a change in
      stereoscopic stimuli composed of dynamic random-dot stereograms from an initially
      flat surface to a stationary sinusoidal grating shown in depth. On the other
      hand, monocular viewing of these stimuli produced no obvious pupillary response.
      This indicates that the pupillary response in the dichoptic experiment was
      induced by the stereo information rather than by any change in the monocular
      stimuli. This finding presents a novel approach for the investigation of stereo
      perception that can also be applied in the clinical environment.

PMID- 15580339
TI  - Cytosolic glucocorticoid receptor expression in the rat vestibular nucleus and
      hippocampus following unilateral vestibular deafferentation.
AB  - It has been suggested that vestibular compensation, the process of behavioural
      recovery that occurs following peripheral vestibular damage, might be partially
      dependent on the release of glucocorticoids (GC) during the early stages of
      recovery from the lesion. One possibility is that glucocorticoid receptors (GRs)
      in the vestibular nucleus complex (VNC) might change following the lesion,
      altering their response to GCs. We sought to test this hypothesis by quantifying
      the expression of cytosolic GRs in the bilateral VNCs at 10 h, 58 h and 2 weeks
      following unilateral vestibular deafferentation (UVD) in rat, using western
      blotting. We also examined GR expression in the CA1, CA2/3 and dentate gyrus (DG)
      subregions of the hippocampus and measured serum corticosterone levels. Compared
      with sham surgery and anaesthetic controls, we found no significant changes in GR
      expression in the ipsilateral or contralateral VNCs at any time post-UVD.
      However, we did find a significant decrease in GR expression in the ipsilateral
      CA1 at 2 weeks post-UVD. Serum corticosterone levels were significantly lower in
      all groups at 58 h post-op. compared to 10 h and 2 weeks; however, there were no
      significant differences between the UVD and control groups at any time point.
      These results suggest that changes in GR expression in the VNC are unlikely to
      contribute to the development of vestibular compensation. However, long-term
      changes in GR expression in CA1 might be related to chronic deficits in
      hippocampal function and spatial cognition following vestibular damage.

PMID- 15580341
TI  - Intracranial involvement in extramedullary hematopoiesis: case report and review
      of the literature.
AB  - Intracranial involvement in extramedullary hematopoiesis (EMH) is rare, but it
      should be suspected in patients with myelofibrosis presenting with chronic severe
      headache. We present a 9-year-old girl with known myelofibrosis whose headaches
      were unresponsive to routine treatment. CT and MRI studies of the brain showed
      diffuse pachymeningeal thickening. CT examinations of the chest and abdomen had
      demonstrated bilateral thoracic paraspinal masses caused by EMH, suggesting the
      possibility that the intracranial involvement might also be related to EMH. The
      diagnosis was confirmed by sulfur colloid isotope scan.

PMID- 15580343
TI  - Distal femur morphometry: a gender and bilateral comparative study using magnetic
      resonance imaging.
AB  - Among the anthropometric factors to be considered, anatomic differences in the
      distal femur and intercondylar notch have been implicated as a cause of the
      different rates of anterior cruciate ligament (ACL) rupture between men and
      women; therefore, in this study our aim was to evaluate a number of morphometric
      measurements in the distal part of the femur. Two hundred knee MRI examinations
      were analyzed: 56 male right, 44 male left, 42 female right and 58 female left.
      Measurements of the intercondylar height (ICH), intercondylar width (ICW), medial
      condylar width (MCW), lateral condylar width (LCW) and epicondylar width (EW)
      were obtained. The notch shape index (NSI) was also calculated. Statistical
      analysis for comparisons was done by Student's t-test. Correlations between the
      parameters studied were calculated by Pearson correlation coefficients.
      Significant bilateral differences were not found (p > 0.05). In all measurements,
      males showed significantly greater values than females (p < 0.001). No difference
      was seen in the NSI between males and females (p > 0.05). Conversely a
      significant association was obtained between age and all parameters. We conclude
      that the results of this study may be useful for anatomic evaluation of the
      distal femur region prior to orthopaedic operations.

PMID- 15580344
TI  - Integrating applied anatomy in surgical clerkship in a problem-based learning
      curriculum.
AB  - Little attention has been given to structured teaching of applied anatomy to
      senior medical students in problem-based learning (PBL) medical schools. A course
      named "Anatomical Principles in Surgical Practice" was introduced at the Arabian
      Gulf University (AGU) in 2001 for fifth- and sixth-year medical students during
      their surgical clerkship rotation. The course aims to emphasize, update and
      integrate applied anatomical concepts that are essential for surgical practice.
      The course consists of 15 interactive sessions held weekly to ensure topics
      coincide with the surgical problem-solving sessions. A questionnaire was
      administered to students completing their surgical rotations (n = 131) seeking
      their perceptions about the new course during the academic years 2001, 2002 and
      2003. To measure learning outcome, 70 students were also given pre- and post
      tests. Positive responses were given by 85.2% of the students for course
      arrangement, by 92.0% for course content, by 88.3% for clinical correlation, by
      95.2% for level of teaching and by 87.2% for overall judgment. The students' mean
      scores in the post-test (71.7%+/-11.7) was significantly higher than their mean
      scores in the pre-test (42.3%+/-12.6, p < 0.001). Students liked the course and
      reported feeling more confident in correlating anatomy with surgery during their
      rotations. By extending anatomical teaching into the clerkship phase, a link
      between basic medical and clinical sciences has been established that further
      enhances vertical integration within a PBL curriculum in a spiral fashion.

PMID- 15580345
TI  - Morphological description of combined variation of distal attachments of
      fibulares in a foot.
AB  - An interesting case of peculiarity of the distal attachment of the three fibular
      muscles is reported in the left foot of a male adult cadaver of Indian origin.
      The fibularis brevis, just inferior to the fibular malleolus, gave off an
      additional slender tendon anteromedial to its main tendon. This was attached to
      the dorsal digital expansion of the little toe while its main tendon was inserted
      to the customary bone. The tendon of fibularis longus on the plantar aspect just
      medial to the cuboid tunnel received a prominent slip of attachment of the tendon
      of tibialis posterior. The fibularis tertius had two parallel-running tendons
      attached to the bases of the fourth metatarsal and the fourth and fifth
      metatarsals respectively. The combined variation of the three fibulares in a
      single foot has not been reported previously. The more distal attachment of the
      fibularis brevis in this case is a regression in evolution. Weakness of both the
      fibularis brevis and fibularis longus is found in pes cavovarus. The former can
      be used as a rotational graft in soft tissue loss of the leg.

PMID- 15580346
TI  - Anterior innervation of the proximal tibiofibular joint.
AB  - Mucoid cysts compressing the common peroneal nerve have been reported. Whether
      these cysts are schwannoma or are synovial in nature is the subject of
      controversy in the medical literature. To contribute to this debate, the present
      study was designed to detail the anterior innervation of the proximal
      tibiofibular joint. We dissected 10 knees of five fresh cadavers after staining
      the tibiofibular joint under fluoroscopic guidance. Through a lateral approach
      near the fibular head, the common peroneal nerve was isolated then dissected
      distally to determine whether it or its branches ramified over the proximal
      tibiofibular joint. In all 10 legs, only one collateral branch was observed on
      the common peroneal nerve proximal to its terminal division. This collateral sent
      a branch to the proximal tibiofibular joint before penetrating the tibialis
      anterior muscle. The articular branch coursed in a superior and posterior
      direction approximately 1 cm to attain the tibiofibular joint. In no specimen did
      the deep or superficial peroneal nerves send a twig to the tibiofibular joint.
      This study confirms and clarifies prior descriptions of the innervation of the
      anterior aspect of the proximal tibiofibular joint. It clarifies the mechanisms
      of compression of the common peroneal nerve by synovial cysts that originate from
      the proximal tibiofibular joint and provides anatomical landmarks that should
      facilitate complete resection of these cysts.

PMID- 15580348
TI  - Suppressive effects of hyaluronan on MMP-1 and RANTES production from
      chondrocytes.
AB  - The purpose of the study was to examine the effects of hyaluronan (HA) on human
      chondrocytes in terms of production of MMP-1 and RANTES. Chondrocytes were
      obtained from patients with osteoarthritis (OA) or femoral neck fracture
      (control). Chondrocytes in monolayer culture were treated with various molecular
      weights (1.2, 50, 800 and 1,900 kD) of HA and then stimulated with IL-1beta.
      Production and expression of MMP-1 and RANTES were quantified by ELISA and real
      time polymerase chain reaction (PCR). The response was blocked by anti-CD44
      antibody. Production of MMP-1 was significantly suppressed by both 800- and 1,900
      kD HA, while production of RANTES was suppressed by 1,900-kD HA. Expression of
      MMP-1 and RANTES mRNA was inhibited by 1,900-kD HA. Suppressive effects of HA on
      production of MMP-1 were canceled by treatment of anti-CD44 antibody. Higher CD44
      expression was found in OA chondrocytes than in those of control. High-molecular
      weight HA suppressed MMP-1 and RANTES production, mediated partly by CD44-HA
      interaction.

PMID- 15580349
TI  - Comparison of the effects of alendronate and risedronate on bone mineral density
      and bone turnover markers in postmenopausal osteoporosis.
AB  - The aim of the study was to compare the effects of once-weekly alendronate sodium
      and daily risedronate sodium treatment on bone mineral density (BMD) and bone
      turnover markers in postmenopausal osteoporotic subjects. For this purpose, 50
      patients were included in this study and randomly classified into two groups.
      Group I (n=25) received risedronate (5 mg/day) and group II (n=25) received
      alendronate Na (70 mg/week). The study duration was limited to 12 months. The
      efficacy of the treatment was evaluated by BMD measurements at spine and hip at
      6th and 12th months of the treatment, as well as by the measurement of bone
      turnover markers such as serum osteocalcin (OC), bone-specific alkaline
      phosphatase (BASP), urine deoxypyridinoline (DPD) and calcium/creatine ratio in
      24-h urine at 1st, 3rd, 6th and 12th months. The evaluation of the changes in BMD
      in all regions revealed a significant increase in BMD in both groups compared to
      baseline values except for spine (L2-L4) in alendronate group at 6th and 12th
      month and femoral neck in risedronate group at 6th month. However, the difference
      in percentage increase in BMD measurements was not statistically significant
      between the two groups at 6th and 12th months. In both groups, serum OC, BSAP and
      urine DPD were found to be significantly attenuated at 1st month of the treatment
      period, and continued to be lowered throughout the 3rd, 6th and 12th months
      (P<0.05). However, there was no statistically-significant difference between both
      groups of patients (P>0.05). In conclusion, our results suggest that both
      treatment protocols provide treatment options of similar efficiency for
      postmenopausal osteoporosis, and have almost-similar effects in enhancing the BMD
      and in slowing the bone turnover. Risedronate seems to have a more potent effect
      in the spinal region than that of alendronate, although this potency was not
      statistically significant.

PMID- 15580350
TI  - Ochronotic arthritis: case reports and review of the literature.
AB  - Alkoptunuria is an inherited autosomal recessive metabolic disorder which is
      caused by the lack of homogentisic acid-oxidase enzyme. It is associated with
      various systemic abnormalities and related to the deposition of homogentisic acid
      pigment in connective tissues. These pigmentary changes are termed "ochronosis".
      We describe two patients with ochronotic arthritis who presented with advanced
      degenerative changes in the lumbo-sacral spine, knee and hip. The literature,
      differential diagnosis and management of this rare condition are reviewed in this
      article.

PMID- 15580351
TI  - Nonspecific interstitial pneumonia pattern as pulmonary involvement of rheumatoid
      arthritis.
AB  - The pathologic patterns of lung involvement were evaluated in 16 patients with
      rheumatoid arthritis (RA). They consisted of six females and ten males, with a
      median age of 67.5 years and diagnosed according to the American Rheumatism
      Association revised criteria. High-resolution computed tomography (HRCT) of the
      lungs was performed in all patients, and honeycomb formation was apparent in
      seven. Histopathologically, seven patients were diagnosed with usual interstitial
      pneumonia (UIP) pattern, seven with nonspecific interstitial pneumonia/fibrosis
      (NSIP) pattern, and two with UIP/NSIP hybrid pattern. There were no apparent
      honeycomb formations on HRCT in patients diagnosed with NSIP pattern. In
      conclusion, the present study demonstrates that NSIP pattern is also a
      significant histologic classification of interstitial pneumonia associated with
      RA.

PMID- 15580353
TI  - Stable genetic transformation of castor (Ricinus communis L.) via Agrobacterium
      tumefaciens-mediated gene transfer using embryo axes from mature seeds.
AB  - A protocol for the transformation of castor embryo axes using the pCAMBIA vector
      1304 in disarmed Agrobacterium tumefaciens strain EHA105 is presented. Co
      cultivated explants were initially subjected to expansion and proliferation on MS
      medium with 0.5 mg l(-1) TDZ followed by three cycles of selection on medium with
      0.5 mg l(-1) BA and increasing concentrations of hygromycin (20-40-60 mg l(-1)).
      Selected shoot clusters were transferred to medium with 0.5 mg l(-1) BA for
      proliferation and 0.2 mg l(-1) BA for shoot elongation. Elongated shoots were
      rooted on half-strength MS medium with 2.0 mg l(-1) NAA. The presence and stable
      integration of the hpt gene was confirmed through PCR, RT-PCR, PCR-Southern blot,
      sequence analysis, Southern blot analysis and PCR analysis of progeny. Southern
      blot analysis of the primary transformants showed single copy integration and
      progeny analysis revealed monogenic inheritance of the introduced gene. This
      paper reports the first successful attempt at producing transgenic castor.

PMID- 15580352
TI  - The advanced glycation end product pentosidine correlates to IL-6 and other
      relevant inflammatory markers in rheumatoid arthritis.
AB  - OBJECTIVE: Oxidative stress and inflammatory processes accelerate the formation
      of advanced glycation end products (AGE), e.g. of pentosidine. The aim of this
      study was to investigate the relationships between levels of pentosidine in serum
      and synovial fluid, proinflammatory cytokines, other markers of inflammatory
      activity, and the state of radiologically visible bone destruction in patients
      with rheumatoid arthritis (RA). OBJECTIVES: One hundred thirty-three nondiabetic
      RA patients and 56 age-matched, healthy subjects were included. Serum and
      synovial fluid pentosidine, erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), and rheumatoid factor levels were determined. In 30 patients, the
      proinflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha and the
      soluble receptors sIL-2R, sIL-6R, sTNF-alpha, and RI/RII were also measured.
      RESULTS: Serum levels of pentosidine were on average significantly higher in RA
      patients than in healthy subjects and correlated significantly to ESR, CRP, and
      serum levels of IL-6. Serum and synovial fluid pentosidine did not show any
      differences. Rheumatoid factor-positive RA patients had higher pentosidine levels
      in the synovial fluid than rheumatoid factor-negative patients. Correlations
      could not be found between pentosidine and the other cytokines or cytokine
      receptors measured. CONCLUSION: The binding of AGE on cell receptors induces
      activation of nuclear factor kappa B, resulting in enhanced synthesis of
      proinflammatory cytokines. Moreover, AGE generation may also lead to the
      formation of new, immunologically relevant epitopes at synovial proteins. Both
      mechanisms could contribute to initiation and perpetuation of the inflammatory
      and destructive processes in RA.

PMID- 15580355
TI  - HYL1 gene maintains venation and polarity of leaves.
AB  - For genetic analysis of the mechanism of leaf curvature, we chose hyl1 mutant of
      Arabidopsis as a model for dissection of leaf venation pattern and
      adaxial/abaxial polarity. In leaves of hyl1 mutants that were hyponastic and
      curved upward, the complexity of the secondary veins was reduced, and the
      discontinuity of veins increased. In the lateral areas of the leaves where
      transverse curvature arises, dorsoventral polarity was lost due to the unclear
      spongy cells, and the epidermal cells became smaller on the adaxial surface than
      those of the abaxial surface, whereas the number of epidermal cells on the two
      surfaces were almost the same. In this case, less complexity of venation,
      decreased cell growth on the adaxial surface was attributed to leaf curvature. To
      depict the role of HYL1 in leaf venation and polarity, we constructed pHYL1:: GUS
      to drive the uidA (beta-glucuronidase) gene, and observed that the GUS signal
      appeared primarily in the petioles and mid-veins of rosette leaves, and were
      restricted to vascular tissues, demonstrating that HYL1 promoter directs the
      process of leaf venation by the uneven expression of the HYL1 gene in leaves. In
      situ hybridization indicates that HYL1 gene is preferentially expressed in leaf
      blades as well as vasculature. In curved leaves of hyl1 mutants, the expression
      level of adaxial identity gene REV was increased and the expression position
      restricted mainly in vasculature and on both sides of growing leaves near the
      margins while expression of the miR165 gene was remarkably reduced, suggesting
      that HYL1 maintain venation and polarity of growing leaves by altering the level
      of microRNA that direct the cleavage of REV transcripts.

PMID- 15580356
TI  - A case of hyperinsulinism/hyperammonaemia syndrome: usefulness of the oral
      protein tolerance for the evaluation of treatment.

PMID- 15580357
TI  - Mucolipidosis II presenting as severe neonatal hyperparathyroidism.
AB  - Mucolipidosis II (ML II or I-cell disease ) (OMIM 252500) is an autosomal
      recessive lysosomal enzyme targeting disorder that usually presents between 6 and
      12 months of age with a clinical phenotype resembling Hurler syndrome and a
      radiological picture of dysostosis multiplex. When ML II is severe enough to be
      detected in the newborn period, the radiological changes have been described as
      similar to hyperparathyroidism or rickets. The biological basis of these findings
      has not been explored and few biochemical measurements have been recorded. We
      describe three unrelated infants with ML II who had radiological features of
      intrauterine hyperparathyroidism and biochemical findings consistent with severe
      secondary neonatal hyperparathyroidism (marked elevation of serum parathyroid
      hormone and alkaline phosphatase levels). The vitamin D metabolites were not
      substantially different from normal and repeatedly normal calcium concentrations
      excluded vitamin D deficiency rickets and neonatal severe hyperparathyroidism
      secondary to calcium-sensing receptor gene mutations (OMIM 239200). The
      pathogenesis of severe hyperparathyroidism in the fetus and newborn with ML II is
      unexplained. We hypothesize that the enzyme targeting defect of ML II interferes
      with transplacental calcium transport leading to a calcium starved fetus and
      activation of the parathyroid response to maintain extracellular calcium
      concentrations within the normal range. CONCLUSION: Newborns with mucolipidosis
      II can present with radiological and biochemical signs of hyperparathyroidism.
      Awareness of this phenomenon may help in avoiding diagnostic pitfalls and
      establishing a proper diagnosis and therapy.

PMID- 15580358
TI  - Haemophilia A in two premature infants.
AB  - The incidence of prematurity in Germany is about 10% and premature infants with
      haemophilia A (OMIM 306700) are in fact very rare. We report two new cases, one
      born in the 28th gestational week, weighing 1200 g with a factor VIII (FVIII)
      level of 0.03 IU/ml treated with bolus injections of plasma derived FVIII
      concentrate (pdFVIII), and one born at week 30, weighing only 710 g with a factor
      level of <0.01 IU/ml and treated with recombinant FVIII concentrate (rFVIII).
      Recovery of FVIII was 96% in case 1 and 120% in case 2, FVIII half-life was 6 h
      and 8 h, respectively. During FVIII substitution, neither bleeding, thrombosis
      nor inhibitor development were noted in both infants. CONCLUSION: Immediate and
      frequent factor VIII substitution appears to be safe and effective for
      prophylaxis and treatment in premature haemophilic neonates.

PMID- 15580359
TI  - Epidermoid cyst of the spleen with elevated levels of CA125 and carcino-embryonic
      antigen.

PMID- 15580360
TI  - [Increasing importance of opioids in geriatrics].
AB  - BACKGROUND: During the previous 20 years the prescription of opioids for medical
      use has increased steadily. Patients and professionals have great reservations
      about the use of opioids in the elderly. The aim of this study was to describe
      the changes in analgesic therapy in a geriatric clinic during the previous 10
      years. METHOD: The quality and quantity of prescriptions for opioids as well as
      the costs of the analgesic therapy in a large geriatric clinic between 1994 and
      2003 were analyzed. RESULTS: The use of opioids increased steadily from 0.72 mg
      per day and patient in 1994 to 9.50 mg in 2003 (1320%). The introduction of
      sustained release tilidine/naloxone and tramadol led to a change of the
      prescribed forms but only to a slight increase in the total consumption of these
      drugs. In 1994 the average daily cost of analgesic therapy was 15 cents per
      patient compared with 46 cents in 2003. The percentage of analgesics in the
      pharmacological budget increased from 5.6 to 10.8%. CONCLUSION: Dealing with
      opioids should be a part of the training program for all members of the geriatric
      team. Analgesics have come to play an important role in the pharmacological
      budget at least in this geriatric clinic.

PMID- 15580361
TI  - Evaporation of intercepted precipitation from fruit litter of Liquidambar
      styraciflua L. (sweetgum) in a clearing as a function of meteorological
      conditions.
AB  - Interception of precipitation by fruit litter is a poorly understood component of
      the hydrologic cycle in forested ecosystems. Even less well understood is the
      effect of meteorological conditions on the evaporation of precipitation
      intercepted by forest litter. This study sought to examine the influence of
      meteorological conditions on the evaporation of intercepted precipitation by
      fruit litter from Liquidambar styraciflua L. (sweetgum) by deriving and
      calibrating a regression model to estimate evaporation from the fruit litter that
      may be of potential use to forest and watershed managers. Data on evaporative
      losses from the fruit litter used to derive and calibrate the statistical model
      were acquired through a larger field experiment conducted from mid November 2002
      through April 2003. Results from the forward stepwise least squares multiple
      regression model demonstrated that evaporative losses from the fruit litter were
      estimated with a high degree of accuracy based on the amount of water stored,
      solar radiation inputs, and vapor pressure deficit (adjusted R(2)=0.836, F=82.28,
      P<0.00001). The amount of water stored in the fruit litter explained the highest
      proportion of variance in the regression model. Storm to storm comparisons also
      highlighted the importance of solar radiation and wind speed in determining
      evaporation from the fruit litter. The regression model potentially may be used
      in conjunction with a canopy interception model to predict interception losses
      from L. styraciflua dominated forests and plantations.

PMID- 15580362
TI  - A feasibility study of psychosocial group intervention for breast cancer patients
      with first recurrence.
AB  - GOALS OF WORK: The effects of psychosocial group interventions on improving
      quality of life (QOL) for patients with recurrent breast cancer are not well
      known. The objective of this study was to assess the feasibility of a
      psychosocial group intervention in Japanese women with first recurrence of breast
      cancer. PATIENTS AND METHOD: The subjects were consecutively selected from among
      patients who were diagnosed with a first recurrence of breast cancer. We
      conducted a 6-week psychosocial group intervention. QOL was assessed using the
      Profile of Mood States (POMS), the Impact of Event Scale-Revised, the Mental
      Adjustment to Cancer (MAC) scale, and the European Organization for Research and
      the Treatment of Cancer (EORTC) Quality of Life Questionnaire-Cancer 30/Breast
      module 23 (QLQ-C30/Br23) at baseline then immediately and 3 and 6 months after
      completion of the intervention. RESULTS: Among 58 eligible patients, written
      consent was obtained from 28 (48%), and the final evaluation was conducted on 19
      subjects. The repeated measured analysis of variance (ANOVA) revealed a
      significant change in tension-anxiety, depression-dejection, anger-hostility and
      total mood disturbance on the POMS, helplessness/hopelessness on the MAC scale,
      and body image and future perspective on the QLQ-C30/Br23. Dunnett's test
      revealed a significant difference in these scores between baseline and 3 months
      after the intervention but no difference between baseline and 6 months after the
      intervention. CONCLUSION: These results suggested the possibility of a short-term
      effectiveness of the intervention; however the results were inconclusive because
      of selected small samples.

PMID- 15580363
TI  - Outcome research in palliative care: could it represent a new dimension of
      clinical research or clinical practice?
AB  - Outcome research is a new dimension of clinical research, and all fields of
      clinical medicine are involved in this kind of analysis. Overall survival and
      quality of life are the main outcomes identified in clinical oncology. The former
      must be the main outcome whenever possible; the latter has to be the main outcome
      when an improvement of overall survival cannot be expected. It follows that
      quality of life is the main outcome of palliative care, in which the patient
      instead of the disease represents the target of the clinical approach. In our
      critical paper, we review the meaning of clinical outcomes in palliative care,
      classifying the outcomes as main and surrogate outcomes, and the results of the
      trials as indexes of activity and efficacy of a treatment. We also review the
      main randomized clinical trials on the treatment of cancer cachexia, trying to
      define the role of the treatments in cachexia-related symptom control and quality
      of life improvement. Strictly related to outcome analysis is the dimension of
      pharmacoeconomic evaluation. The models of the different designs of
      pharmacoeconomic analysis are revisited in an attempt to conjugate the
      pharmacoeconomic evaluation with the particular dimension of palliative care.

PMID- 15580364
TI  - Nutritional status of cancer patients and its relationship to function in an
      inpatient rehabilitation setting.
AB  - BACKGROUND: Malnutrition is associated with prolonged hospitalization, lower
      survival rate, and various medical complications. However, little is known about
      malnutrition and its relationship with the functional status. We undertook this
      retrospective study to examine whether or not malnutrition affects rehabilitation
      outcome in patients who had undergone cancer rehabilitation. METHODS: We
      conducted a review of the charts of 30 consecutive cancer patients who had been
      admitted to the inpatient rehabilitation unit in a tertiary cancer center, from
      the beginning of March 2001 to the end of April 2001. RESULTS: The patients' mean
      rehabilitation stay was 9 days and their mean age was 58 years (range 22-86
      years). On rehabilitation admission, 15 of the patients (50%) had a below normal
      prealbumin (<18 mg/dl) level (95% confidence interval 31-69%), and on discharge
      10 of the patients (33%) had a below normal prealbumin level (95% CI 17-54%). The
      serum prealbumin concentration level correlated with motor functional
      independence measure scores on admission. After inpatient rehabilitation,
      statistically significant gains in functional independence measure scores
      (P<0.0001) were obtained in patients with below normal admission prealbumin, as
      well as in those whose prealbumin levels were within the normal range; no
      statistically significant difference was found in functional gain between these
      two groups. CONCLUSION: Our study showed that a large number of cancer
      rehabilitation patients had malnutrition. Nevertheless, functional gain was
      achieved in all patients after rehabilitation, whether or not malnutrition was
      present. We conclude that malnourished patients should still be considered
      candidates for rehabilitation.

PMID- 15580365
TI  - Prevalence and clinical characteristics of tuberculosis in rheumatoid arthritis
      patients.

PMID- 15580366
TI  - Microscopic polyangiitis sparing the kidneys in a long-term survivor after
      allogenic bone marrow transplantation and graft-versus-host disease.
AB  - We report an unusual case of microscopic polyangiitis sparing the kidneys in a
      long-term survivor of allogenic bone marrow transplantation. Clinical and
      pathologic studies revealed cutaneous leukocytoclastic vasculitis and isolated
      pulmonary capillaritis. Serological studies revealed "double positive":
      perinuclear antineutrophil cytoplasmic (p-ANCA) antibody testing with anti
      myeloperoxidase (MPO) activity and anti-glomerular basement membrane (anti-GBM)
      antibody. The vasculitis has been successfully controlled with prednisone and
      cyclophosphamide.

PMID- 15580367
TI  - Meadow voles, Microtus pennsylvanicus, can distinguish more over-marks from fewer
      over-marks.
AB  - Is it possible that voles have a sense of number? To address this question, we
      determined whether voles discriminate between two different scent-marking
      individuals and identify the individual whose scent marks was on top more often
      than the other individual. We tested whether voles show a preference for the
      individual whose scent marks was on top most often. If so, the simplest
      explanation was that voles can make a relative size judgement-such as
      distinguishing an area containing more of one individual's over-marks as compared
      to less of another individual's over-marks. We found that voles respond
      preferentially to the donor that provided a greater number of over-marks as
      compared to the donor that provided a lesser number of over-marks. Thus, we
      concluded that voles might display the capacity for relative numerousness.
      Interestingly, female voles were better able than male voles to distinguish
      between small differences in the relative number of over-marks by the two scent
      donors.

PMID- 15580368
TI  - Looking through genomics--from the editors.

PMID- 15580369
TI  - Topical application of mitomycin C prevents epineural scar formation in rats.
AB  - The role of topically applied mitomycin C in preventing postoperative perineural
      fibrosis was examined by gross anatomical dissection and histological analysis in
      rats. The sciatic nerve was exposed bilaterally in 24 Wistar adult male rats, and
      an abrasion injury was produced on the exposed surface of the biceps femoris
      muscle in all animals. In the experimental group, cotton pads soaked with
      mitomycin C (0.5 mg/ml) were placed around the nerves for 5 min, whereas cotton
      pads soaked with saline were applied to the control group. Four weeks after
      surgery, the neurolysis sites were evaluated by blinded surgical dissection.
      Perineural adhesions were graded using a numerical grading scheme. The scar
      tissue formation index was also calculated, and a grading was made according to
      the number of fibroblasts/fibrocytes counted around the epineurium in
      histological evaluation. Mitomycin C-treated nerves showed significantly less
      perineural adhesions than controls. Quantification of the dense connective tissue
      surrounding the nerves revealed a statistically significant reduction around
      nerves treated with mitomycin C, and the number of fibroblast/fibrocytes was also
      significantly reduced. Application of topical mitomycin C might be effective in
      preventing epineural scar formation after neurolysis of peripheral nerves.

PMID- 15580370
TI  - 201Tl-SPECT and 1H-MRS study of benign lateral ventricle tumors: differential
      diagnosis of subependymoma.
AB  - The introduction of computed tomography (CT) and magnetic resonance (MR) imaging
      has resulted in the detection of increasing numbers of asymptomatic
      intraventricular tumors. Establishing the correct preoperative diagnosis is
      important to prevent unnecessary surgical intervention. Our study includes nine
      cases of benign lateral ventricle tumors including two cases of central
      neurocytoma, two of subependymal giant cell astrocytoma, two of pilocytic
      astrocytoma and three of subependymoma treated surgically between 1996 and 2003.
      MR imaging, proton MR spectroscopy ((1)H-MRS) and thallium-201 single photon
      emission computed tomography ((201)Tl-SPECT) were performed in all patients. All
      three types of tumor demonstrated heterogeneous enhancement on MR imaging with
      gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and increased choline
      (Cho) peak and decreased N-acetyl aspartate (NAA) and creatine (Cre) peaks on
      (1)H-MRS. (201)Tl-SPECT showed high uptake of (201)Tl without wash out in all
      cases of central neurocytoma, subependymal giant cell astrocytoma and pilocytic
      astrocytoma, but no uptake in cases of subependymoma. Absence of (201)Tl uptake
      in contrast with enhancement on MR imaging and the (1)H-MRS features of modest
      elevation of the Cho/Cre ratio, reduction of the NAA peak and presence of
      lactate/lipid peaks are characteristic features of subependymomas and useful to
      establish a preoperative diagnosis.

PMID- 15580371
TI  - Diffusion imaging for evaluation of tumor therapies in preclinical animal models.
AB  - The increasing development of novel targeted therapies for treating solid tumors
      has necessitated the development of technology to determine their efficacy in
      preclinical animal models. One such technology that can non-invasively quantify
      early changes in tumor cellularity as a result of an efficacious therapy is
      diffusion MRI. In this overview we present some theories as to the origin of
      diffusion changes as a result of tumor therapy, a robust methodology for
      acquisition of apparent diffusion coefficient maps and some applications of
      determining therapeutic efficacy in a variety therapeutic regimens and animal
      models.

PMID- 15580372
TI  - Linear microstrip surface coil for MR imaging of the rat spinal cord at 4.7 T.
AB  - A new design of RF coil based on a quasi-transverse electromagnetic field is
      described. The coil was developed for the acquisition of MR images of the rat
      spinal cord at 4.7 T. Different materials for the construction of the coil were
      tested, and the best results were obtained with Teflon. The design of the
      microstrip coil enables the investigator to change the length of the coil in a
      longitudinal direction and yields a relatively high signal-to-noise ratio due to
      the restricted field of view. Low RF field penetration depth also helps in
      suppressing motion artifacts generated by, e.g., breathing or heartbeats.

PMID- 15580373
TI  - Evaluation of cartilage repair tissue after biomaterial implantation in rat
      patella by using T2 mapping.
AB  - To evaluate the ability of MR T2 mapping (8.5 T) to characterize ex vivo
      longitudinally, morphologically and quantitatively, alginate-based tissue
      engineering in a rat model of patellar cartilage chondral focal defect.
      Calibrated rat patellar cartilage defects (1.3 mm) were created at day 0 (D0) and
      alginate sponge with (Sp/C+) or without (Sp/C-) autologous chondrocytes were
      implanted. Animals were sacrificed sequentially at D20, D40 and D60 after surgery
      and dissected patellae underwent MRI exploration (8.5 T). T2 values were
      calculated from eight SE images by using nonlinear least-squares curve fitting on
      a pixel-by-pixel basis (constant repetition time of 1.5 s, eight different echo
      times: 5.5, 7.5, 10.5, 12.5, 15.0, 20.0, 25.0 and 30.0 ms). On the T2 map,
      acquired in a transversal plane through the repair zone, global T2 values and
      zonal variation of T2 values of repair tissue were evaluated versus control group
      and compared with macroscopic score and histological studies (toluidine blue,
      sirius red and hematoxylin-eosin). "Partial", "total" and "hypertrophic" repair
      patterns were identified. At D40 and D60, Sp/C+ group was characterized by a
      higher proportion of "total" repair in comparison to Sp/C- group. At D60, the
      proportion of "hypertrophic" repair was two fold in Sp/C- group versus Sp/C+
      group. As confirmed morphologically and histologically, the T2 map also permitted
      the distinction of three types of repair tissue: "total", "partial" and
      "hypertrophic". "Total" repair tissue was characterized by high T2 values versus
      normal cartilage (p<0.05). Zonal variation, reflecting the collagen network
      organization, appeared only at D60 for Sp/C+ group (p<0.05). "Hypertrophic"
      tissue, mainly observed at D60, presented high T2 global values without zonal
      variation with cartilage depth. These results confirm the potency of the MR T2
      map (8.5 T) to characterize macroscopically and microscopically the patterns of
      the scaffold guided-tissue repair of a focal chondral lesion in the rat patella
      ("total", "partial" and "hypertrophic"). On T2 map, three parameters (i.e. MRI
      macroscopic pattern, T2 global values and zonal variation of T2 values) permit to
      characterize chondral repair tissue, as a virtual biopsy.

PMID- 15580374
TI  - In vivo diffusion tensor mapping of the brain of squirrel monkey, rat, and mouse
      using single-shot STEAM MRI.
AB  - The purpose was to assess the potential of half Fourier diffusion-weighted single
      shot STEAM MRI for diffusion tensor mapping of animal brain in vivo. A STEAM
      sequence with image acquisition times of about 500 ms was implemented at 2.35 T
      using six gradient orientations and b values of 200, 700, and 1200 s mm(-2). The
      use of half Fourier phase-encoding increased the signal-to-noise ratio by 45%
      relative to full Fourier acquisitions. Moreover, STEAM-derived maps of the
      relative anisotropy and main diffusion direction were completely free of
      susceptibility-induced signal losses and geometric distortions. Within measuring
      times of 3 h, the achieved resolution varied from 600x700x1000 microm3 for
      squirrel monkeys to 140x280x720 microm3 for mice. While in monkeys the accessible
      white matter fiber connections were comparable to those reported for humans,
      detectable fiber structures in mice focused on the corpus callosum, anterior
      commissure, and hippocampal fimbria. In conclusion diffusion-weighted single-shot
      STEAM MRI allows for in vivo diffusion tensor mapping of the brain of squirrel
      monkeys, rats, and mice without motion artifacts and susceptibility distortions.

PMID- 15580375
TI  - Measurements of T1 and T2 relaxation times of colon cancer metastases in rat
      liver at 7 T.
AB  - The purpose of this study was to investigate the magnetic resonance imaging (MRI)
      characteristics of colon cancer metastases in rat liver at 7 T. A dedicated RF
      microstrip coil of novel design was built in order to increase the signal-to
      noise ratio and, in combination with respiratory triggering, to minimize motion
      artifacts. T1- and T2-weighted MR imaging was performed to follow tumor growth.
      T1-weighted images provided a good anatomical delineation of the liver structure,
      while the best contrast between metastases and normal liver tissue was achieved
      with T2-weighted images. Measurements of T1 and T2 relaxation times were
      performed with inversion recovery FLASH and Carr-Purcell-Meiboom-Gill and
      inversion recovery FLASH imaging sequences, respectively, for quantitative MR
      characterization of metastases. Both the T1 and T2 of the metastases were
      significantly higher than those of normal liver tissue. Further, an increase in
      the T1 relaxation time of the metastases was observed with tumor growth. These
      findings suggest that quantitative in vivo MR characterization provides
      information on tumor development and possibly response to therapy, though
      additional studies are needed to elucidate the correlation between the changes in
      relaxation times and tumor microenvironment.

PMID- 15580376
TI  - Vessel size imaging using low intravascular contrast agent concentrations.
AB  - Vessel size index (VSI) measurements have been validated on rats bearing a glioma
      with high doses of contrast agent. The aim of this study was to evaluate the
      impact of using a reduced dose of contrast agent, necessary for clinical trials.
      Experiments were performed on rats at three doses of AMI-227 and clearly show
      higher VSI values at lower doses, whatever the region of interest (contralateral,
      peritumoral and intratumoral tissue). These results are in good correlation with
      Monte-Carlo simulations on healthy brain and suggest that only relative values
      can be obtained at clinical contrast agent doses and magnetic fields.

PMID- 15580378
TI  - Role of hypermethylation on carcinogenesis in the pancreas.
AB  - Pancreatic cancer is a disease with a dismal outcome and a 5-year survival rate
      of under 5%. Recent studies have shown that pancreatic cancer consists of an
      accumulation of genetic and epigenetic alterations during tumor development as in
      other human cancers. Therefore, new diagnostic methods for early detection and
      more effective therapeutic strategies based on a better understanding of the
      molecular biology of pancreatic cancer are urgently required. Recently, promoter
      hypermethylation of cancer-related genes has emerged as an important mechanism in
      carcinogenesis. The present review summarizes an overview of the alterations of
      promoter hypermethylation in pancreatic cancer, and suggests that the further
      study of promoter hypermethylation involvement in pancreatic cancer and the
      delineation of molecular mechanisms involved may lead to an improvement in the
      outcome of this aggressive disease.

PMID- 15580377
TI  - 23Na microscopy of the mouse heart in vivo using density-weighted chemical shift
      imaging.
AB  - The mouse has become an important animal model for human cardiac disease, and the
      development of techniques for non-invasive imaging of the mouse heart in vivo is,
      therefore, of great potential interest. Previous magnetic resonance imaging
      studies have concentrated on pathologically induced changes in cardiac structure
      and dynamics by acquiring proton images. Further information can be gained by
      studying cardiac function and physiology using other nuclei, for example, sodium.
      Sodium imaging of such a small structure presents considerable technical
      challenges. In this work we show the first sodium images of the mouse heart, with
      an isotropic spatial resolution of 1 x 1 x 1 mm, acquired in a time of 1.5 h. The
      ventricles, septum and myocardium are readily distinguishable in these images,
      which were acquired through the combination of 3D density-weighted chemical shift
      imaging, optimized instrumentation, and a high magnetic field strength (17.6 T).
      Measurements of the myocardial:blood sodium concentration in the left and right
      ventricles agree well with theoretical values.

PMID- 15580379
TI  - Cystic hydatid disease: current trends in diagnosis and management.
AB  - Cystic echinococcosis is endemic in certain parts of the world. The growth of the
      cyst is often slow, and the liver and lungs are the most frequently involved
      organs. Diagnosis is based on clinical signs and symptoms and epidemiological
      data, while ultrasonography is important for the classification of hydatid cysts.
      Although certain types of hydatid cysts are successfully treated by percutaneous
      aspiration, injection, and reaspiration, surgery remains the treatment of choice.
      We reviewed the current trends in the diagnosis and management of cystic
      echinococcosis, with special emphasis on hepatic and pulmonary involvement.

PMID- 15580380
TI  - A randomized prospective study of complications between general surgery residents
      and attending surgeons in near-total thyroidectomies.
AB  - PURPOSE: Recurrent laryngeal nerve palsy and hypoparathyroidism are the most
      common and serious complications after thyroid operations. Surgeon experience has
      been defined as a significant factor in the number of complications occurring in
      thyroid surgery. There has so far been no prospective randomized study that
      compares the complication rates between residents and the attending surgeon in
      statistically similar patient groups in which all of the patients undergo the
      same type of thyroid surgery by the same surgical team. In this prospective study
      the performances of residents and attending surgeons were evaluated and compared
      according to the complication rates in near-total thyroidectomies. METHODS: One
      hundred and fifty-two patients underwent near-total thyroidectomies between April
      2001 and May 2003. The number of randomly selected patients operated on by
      residents at the level of postgraduate year two, under the direct supervision of
      an attending surgeon, and the number of patients operated on by attending
      surgeons were 78 and 74, respectively. All patients had preoperative and
      postoperative videolaryngostroboscopic examinations of the vocal cords and serum
      calcium level evaluation. RESULTS: The rates of temporary vocal cord paralysis
      with respect to the nerves at risk for residents and attending surgeons were 3.7%
      and 2.7%, respectively. The temporary hypoparathyroidism rate was 8.1% for
      attending surgeons, whereas it was found to be 6.4% for residents. Neither any
      cases of permanent vocal cord paralysis nor permanent hypoparathyroidism were
      detected. CONCLUSION: Our results indicate that the complication rates in near
      total thyroidectomies performed by residents and attending surgeons are similar.
      Thyroid surgery can therefore be safely and effectively performed by residents
      under close supervision.

PMID- 15580381
TI  - Conservative treatment of postpneumonic thoracic empyema in children.
AB  - PURPOSE: Many treatment modalities have been described for thoracic empyema in
      children but the optimal timing of appropriate treatment remains controversial.
      The aim of this study is to find out the outcome of postpneumonic empyema in
      children after a conservative approach. METHODS: The reports of patients who were
      admitted to our hospital from January 1990 to October 2002 with a diagnosis of
      postpneumonic thoracic empyema were reviewed retrospectively. The comparative
      data were age, duration of prehospital illness, complaints, blood and pleural
      fluid analyses, radiological evaluations, microbiological studies, modes of
      treatment, duration of chest tube drainage, and length of hospital stay. RESULTS:
      A total of 115 patients (65 males and 50 females), aged from 3 months to 13
      years, were evaluated. The most common symptoms were fever (96.5%), cough
      (85.2%), and dyspnea (50.4%). Chest X-rays revealed a minimal collection in 22
      (19.2%), a moderate collection in 40 (34.8%), and a massive collection in 53
      patients (46%). Staphylococcus aureus was the most common microorganism isolated
      from the bacterial cultures and Mycobacterium tuberculosis was the next most
      common. Twelve patients (10.4%) underwent surgical decortication. The mean
      duration of chest drainage was 10.1 +/- 1.39 days. The mean hospitalization
      period was 24.2 +/- 6.15 days and it was significantly shorter in patients with a
      minimal collection than in those with a massive collection (13.9 +/- 2.21 vs
      28.47 +/- 6.38 days, P < 0.01). CONCLUSIONS: The majority of postpneumonic
      thoracic empyema cases in children can be successfully treated with a
      conservative approach. Detailed investigations should also be done to rule out
      tuberculosis in these patients.

PMID- 15580382
TI  - One-lung ventilation for video-assisted thoracoscopic interruption of patent
      ductus arteriosus.
AB  - PURPOSE: Video-assisted endoscopic techniques have recently been employed in
      congenital heart surgery for patent ductus arteriosus (PDA) interruption. We
      report our preliminary experience of using a new technique of single-lung
      ventilation to perform video-assisted thoracoscopic PDA interruption (VATS-PDA)
      in small infants and children. METHODS: Sixteen infants with a mean body weight
      of 6.5 +/- 2.4 kg (range 2.6-12.8 kg) underwent VATS-PDA under selective right
      lung ventilation using a 2-F balloon catheter for arterial embolectomy. RESULTS:
      We did not need to reposition the retractor or reinflate the atelectatic lung, as
      there was no transient hypoxia or hypercarbia. The mean procedure time was 81 +/-
      27 min (range 45-145 min) and all patients, with the exception of one with a
      total anomalous pulmonary venous connection, were extubated in the operating
      room. CONCLUSION: This technique using single-lung ventilation for infants and
      small children was safe and effective in providing pediatric thoracic access and
      exposure within confined and delicate anatomic spaces.

PMID- 15580383
TI  - Postoperative renal function after elective abdominal aortic aneurysm repair
      requiring suprarenal aortic cross-clamping.
AB  - PURPOSE: To examine postoperative renal function after suprarenal aortic cross
      clamping performed without renal hypothermia in patients undergoing elective
      abdominal aortic aneurysm (AAA) surgery. METHODS: Between 1991 and 2000, 18
      patients underwent surgery for a juxtarenal AAA, which required a suprarenal
      aortic cross-clamp. All AAAs were repaired with a proximal anastomosis just below
      the renal arteries. We divided the patients into two groups according to the
      duration of the renal ischemia: <45 min (n = 12) and > or =45 min (n = 6). The
      postoperative changes in renal function were analyzed. RESULTS: There were no
      hospital deaths and none of the patients needed permanent hemodialysis. The
      postoperative peak in the serum creatinine level after suprarenal cross-clamping
      for > or =45 min was significantly higher than that after cross-clamping for <45
      min. The percentage changes in serum creatinine and blood urea nitrogen were
      correlated positively with the duration of renal ischemia, and were significantly
      greater in the group with renal ischemia of <45 min than in the group with
      prolonged renal ischemia (> or =45 min). CONCLUSIONS: Suprarenal aortic cross
      clamp without performing renal hypothermia is safe and able to be tolerated well
      by the patient during elective AAA surgery, although careful attention must be
      paid to limiting the period of renal ischemia.

PMID- 15580384
TI  - Serum interleukin-12 levels in patients with gastric cancer.
AB  - PURPOSE: To evaluate the immunological status of patients with gastric cancer
      before surgery, we investigated the relationship between serum interleukin-12 (IL
      12) levels and clinicopathological factors. METHODS: We measured serum IL-12
      levels in 127 patients with gastric cancer and 35 healthy controls, by a sandwich
      enzyme-linked immunosorbent assay using the Human IL-12 +p40 Immunoassay kit.
      RESULTS: The serum IL-12 levels in the patients with gastric cancer were
      significantly higher than those of the healthy controls (P < 0.05). There were no
      significant differences in disease stage or gross appearance among the cancer
      groups, but the serum IL-12 levels in patients with T4 disease were significantly
      lower than those in patients with T1, T2, or T3 (P < 0.01). There were no
      significant differences in serum IL-12 levels between patients with and those
      without lymph node, liver, or peritoneal metastasis. The serum IL-12 levels in
      patients with distant metastasis were significantly lower than those in patients
      without distant metastasis (P < 0.02). There were no significant differences in
      the serum IL-12 levels according to classification by histopathological findings.
      Analysis with the linear correlation coefficient showed no significant
      correlation between serum IL-12 and serum carcinoembryonic antigen, carbohydrate
      antigen (CA) 19-9, CA 72-4, alpha-fetoprotein, or immunosuppressive acidic
      protein. However, there was a significant relationship between serum IL-12 levels
      and soluble IL-2 receptor levels (r = 0.53, P < 0.01). CONCLUSION: Serum IL-12
      levels in patients with far-advanced gastric cancer were significantly lower than
      those in patients with less-advanced gastric cancer. This is because macrophages
      in patients with far-advanced cancer would be hectic and unable to produce
      sufficient IL-12.

PMID- 15580385
TI  - Laparoscopic colectomy versus open colectomy for colorectal carcinoma: a
      retrospective analysis of patients followed up for at least 4 years.
AB  - PURPOSE: To compare the long-term outcome of laparoscopic-assisted colectomy
      (LAC) with that of open colectomy (OC) for carcinoma in patients followed up for
      a minimum of 4 years. METHODS: We reviewed the medical records of 118 patients
      who underwent LAC between January 1993 and September 1999, and compared the
      results with those of 163 selected patients who underwent OC during the same
      period. RESULTS: Curative surgery was performed in 114 of the LAC patients.
      Because recurrence did not develop in any of the patients with stage I cancer, we
      analyzed the patterns of recurrence only in those with stage II or III disease;
      58 patients were analyzed in the laparoscopic group and 130 in the open colectomy
      group. In the LAC group, 7 (12.1%) patients had recurrence after a median follow
      up of 58 months and in the OC group, 19 (14.6%) patients had recurrence after a
      median follow-up of 56.5 months. The 5-year disease-free rate was similar in the
      LAC (87.8%) and OC (85.5%) groups (P = 0.75 by the log-rank test). CONCLUSIONS:
      Laparoscopic-assisted colectomy is effective and safe for the treatment of
      colorectal carcinomas under the criteria used in this study. However, further
      validation of these results is recommended.

PMID- 15580386
TI  - Improved healing of small-caliber, long-fibril expanded polytetrafluoroethylene
      vascular grafts by covalent bonding of fibronectin.
AB  - PURPOSE: To evaluate the intermediate performance of small-caliber, long-fibril
      expanded polytetrafluoroethylene (ePTFE) vascular grafts pretreated with covalent
      bonding of fibronectin in dogs. METHODS: Small-caliber (4 mm), long-fibril (60
      microm), ePTFE vascular grafts, 10 cm in length, were pretreated by covalent
      bonding of fibronectin. Bilateral iliac grafting was done in dogs using a
      fibronectin-bonded graft on one side and a nonbonded control graft on the other
      side. The grafts were retrieved 12 weeks after implantation, and subjected to
      histomorphometric analysis. RESULTS: Although the patency rates of the
      fibronectin-bonded and control grafts were the same (3/7, 43%), the fibronectin
      bonded grafts showed almost complete neointimal healing, whereas the nonbonded
      control grafts showed only partial neointimal healing, proximally and distally.
      CONCLUSIONS: Small-caliber, long-fibril ePTFE vascular grafts with covalent
      bonding of fibronectin achieved almost complete neointimal healing by the time of
      retrieval at 12 weeks. This indicates that, with further modifications, our new
      technique for covalent bonding of fibronectin has great potential in the
      development of small-caliber arterial prosthetic grafts.

PMID- 15580387
TI  - Optimal timing for surgery after adriamycin treatment in rats.
AB  - PURPOSE: To determine the optimal timing of surgery after adriamycin treatment,
      we investigated the time-related effect of adriamycin on wound healing over a
      long period. METHODS: We divided 119 female Sprague-Dawley rats into seven
      treatment groups. Group 1 was subjected to laparatomy only. All the other groups
      were given 8 mg/kg adriamycin intravenously followed by laparotomy on the same
      day (group 2), 7 days later (group 3), 14 days later (group 4), 21 days later
      (group 5), 28 days later (group 6), or 35 days later (group 7). On postoperative
      day 7, the sutures were removed, abdominal bursting pressure was measured, and
      tissue samples were taken for histopathological evaluation and analysis of
      hydroxyproline content. RESULTS: Bursting pressures were significantly lower in
      groups 3, 4, 5, and 6 than in group 1. The hydroxyproline content and
      histopathological evaluation supported these findings. CONCLUSIONS: Our results
      showed that the optimal timing for surgery after adriamycin treatment is before
      the 7th day or after the 35th day. If surgery is performed between these days,
      there is a high risk of impaired wound healing.

PMID- 15580388
TI  - The role of transforming growth factor alpha formulation on aspirin-induced ulcer
      healing and oxidant stress in the gastric mucosa.
AB  - PURPOSE: Transforming growth factor (TGF) alpha accelerates wound healing,
      especially in gastric ulcers. Transforming growth factor alpha can be affected by
      acid and pepsin in the gastric juice. Oxidative stress also plays a role in the
      formation of gastric lesions. This study was designed (1) to investigate the
      effects of microemulsion dosage form on the healing of gastric ulcers, and (2) to
      determine the relationship between oxidative mechanisms and TGF-alpha during
      ulcer healing. METHODS: Gastric ulcers were induced in Wistar rats (male, 200 +/-
      25 g), by 150 mg/kg acidified aspirin application. The animals were divided into
      five groups consisting of 7-11 animals. The rats were killed after ulcer
      induction with aspirin (acute ulcer), or 2 days after ulcer induction (chronic
      ulcer), or after the daily application of microemulsion and TGF-alpha for 2 days.
      The ulcer area was measured planimetrically. Thiobarbituric acid reactive
      substance, glutathione, and gastric mucus levels of tissues were measured by
      spectrophotometric methods. The total nitric oxide level was measured by a
      VCl3/Griess assay. Statistical comparisons were made by an analysis of variance
      and the Mann-Whitney U-test. RESULTS: The ulcer area and malondialdehyde level of
      gastric tissue both decreased and the glutathione level increased to intact
      gastric tissue levels, while the mucus and total nitric oxide levels increased
      significantly after the application of intragastric TGF-alpha. CONCLUSION: These
      findings suggest that TGF-alpha accelerates the healing process after aspirin
      induced gastric injury, and a relationship was observed between this application
      and the oxidative reactions.

PMID- 15580389
TI  - Heparin-induced thrombocytopenia after coronary artery bypass grafting with
      cardiopulmonary bypass: report of a case.
AB  - A 79-year-old man was transferred to our hospital with severe chest pain and a
      suspected diagnosis of acute myocardial infarction. Emergency cardiac
      catheterization showed triple-vessel coronary artery disease, and we performed
      coronary artery bypass grafting under cardiopulmonary bypass (CPB). Continuous
      hemodiafiltration was started for acute renal failure postoperatively, and
      heparin was given as an anticoagulanting agent. By 9 days after the initiation of
      heparin therapy, his platelet count had fallen and a deep vein thrombosis had
      formed in his left leg. We suspected heparin-induced thrombocytopenia (HIT), and
      immediately discontinued the heparin, implementing danaparoid (Orgaran) instead,
      following which the platelet count recovered. Heparin-induced thrombocytopenia,
      which causes thrombosis, is a serious side effect of heparin therapy and few
      cases of HIT associated with CPB surgery have been reported in Japan.

PMID- 15580390
TI  - Accessory splenectomy with gastroesophageal devascularization for recurrent
      hypersplenism and refractory bleeding varices in a patient with liver cirrhosis:
      report of a case.
AB  - We report a case of recurrent thrombocytopenia associated with symptomatic
      enlargement of an accessory spleen, 2 years after splenectomy, in a 36-year-old
      man with posthepatitic liver cirrhosis. The patient suffered three episodes of
      variceal bleeding, but the esophageal varices were not eradicated by two sessions
      of endoscopic injection sclerotherapy and endoscopic band ligation. Abdominal
      ultrasonography and computed tomography showed a giant accessory spleen (6 x 6 x
      5 cm), gallbladder stones, and complete postsplenectomy splenomesoportal
      thrombosis. Subsequent 99mTc scintigraphy confirmed the presence of a functioning
      residual splenic nodule. Thus, we performed gastroesophageal devascularization
      (Hassab-Paquet procedure) with accessory splenectomy and cholecystectomy, after
      which the platelet count normalized and no further variceal bleeding occurred
      during 17 months of follow-up. To our knowledge, this is the first report in the
      English medical literature of accessory splenectomy for recurrent
      thrombocytopenia in a patient with liver cirrhosis.

PMID- 15580391
TI  - Successful surgical ligation under intraoperative portal vein pressure monitoring
      of a large portosystemic shunt presenting as an intrapulmonary shunt: report of a
      case.
AB  - We report a rare case of patent ductus venosus (PDV) with collapsed intrahepatic
      portal branches and an intrapulmonary shunt. Excellent improvement of the
      intrahepatic portal vein flow was achieved by ligating the large ductus venosus
      under intraoperative portal vein pressure (PVP) monitoring. A 3-year-old boy
      being followed up for hypergalactosemia at a local hospital was found to have
      mild lip cyanosis, exertional dyspnea, clubbed fingers, and mild liver
      dysfunction with high levels of transaminase and ammonia. Cardiac catheterization
      indicated an intrapulmonary shunt with a ratio of 33%. Abdominal ultrasonography
      and computed tomography showed remarkable communication between the portal vein
      and the inferior vena cava. We performed laparotomy and successfully ligated the
      PDV under PVP monitoring. The PVP did not increase until the catheter was removed
      7 days postoperatively. The patient's liver function test results returned to
      normal within 2 weeks. His serum galactose level was 0 mg/dl after drinking milk,
      and his SpO2 in room air and exertional dyspnea also improved. He was discharged
      18 days after his operation, without any complications. We propose that ligation
      of a PDV under PVP monitoring could be a treatment of choice, bearing in mind
      that PDV is associated with collapsed intrahepatic portal branches.

PMID- 15580392
TI  - Primary peritonitis associated with streptococcal toxic shock-like syndrome:
      report of a case.
AB  - Several reports over the past 15 years describe severe group A streptococcal
      infections causing septic shock, soft-tissue necrosis, and multiple organ
      failure; a phenomenon known as streptococcal toxic shock-like syndrome (TSLS).
      However, primary peritonitis associated with TSLS is rare. We report the case of
      a 40-year-old man admitted with pain in both thighs, hypotension, and severe
      abdominal pain. His daughter had been diagnosed with streptococcal pharyngitis 3
      days earlier. We performed an emergency laparotomy for peritonitis, and culture
      of the ascites was positive for group A beta -hemolytic streptococcus (GAS).
      Further serotyping of the isolated GAS strain revealed the T-type 22 and the
      pyrogenic exotoxin gene, spe-C. The criteria for TSLS were clearly met, including
      the isolation of GAS from ascites, hypotension, liver failure, renal failure,
      coagulopathy, myositis, and a generalized erythematous macular rash with
      desquamation.

PMID- 15580393
TI  - Closed subfascial ligation of incompetent perforating veins of the lower
      extremities.
AB  - The purpose of this study was to determine the effectiveness of minimally
      invasive surgical procedures for interrupting incompetent perforating veins of
      the lower limb. A closed subfascial ligation was performed in 20 patients who had
      incompetent perforating veins in 28 limbs as diagnosed by a clinical examination
      and duplex scanning. Two small transverse incisions measuring 5-10 mm in length
      were made on both sides of the incompetent perforating vein. Using an aneurysmal
      needle, a suture (polypropylene No. 1) was placed in the subfascial plane to
      encircle the incompetent perforating vein from all directions. Next, this suture
      was tied through two incisions to ligate this perforator. The mean follow-up
      period was 26 months. The ligation of the incompetent perforators was successful
      in 27 of 28 limbs and no wound complications were observed. A closed subfascial
      ligation of incompetent perforating veins of the lower limbs is thus considered
      to be easy to perform, not overly invasive, safe, and to also have very
      encouraging results.

PMID- 15580394
TI  - Heartburn in primary care: problems below the surface.
AB  - Heartburn is a common physiological event often associated with an underlying
      occurrence of gastroesophageal reflux disease (GERD). Studies show that GERD is a
      highly prevalent and chronic condition that significantly impacts on the
      patient's quality of life (QoL) and, in the long term, increases the risk for
      developing esophageal adenocarcinoma, more commonly referred to as Barrett's
      esophagus. Data indicate that symptom severity is a poor predictor of either the
      presence of erosive mucosal lesions or the development of complications. Given
      that lifestyle modifications are often insufficient for long-term treatment of
      GERD, drugs that inhibit gastric acid production--such as the proton pump
      inhibitors (PPIs)--are now the most effective strategy. Although generally well
      tolerated, the potential of PPIs for interactions with other drugs needs to be
      considered. This review discusses the symptoms and risk factors associated with
      GERD, possible links to Helicobacter pylori infection, and effective treatment
      strategies within a primary care setting.

PMID- 15580395
TI  - Effect of single-dose administration of recombinant interferon-alpha2b on gastric
      myoelectrical activity in patients with chronic hepatitis C.
AB  - BACKGROUND: Upper abdominal complaints during interferon therapy may result from
      impaired gastric motility and/or evacuatory function. We examined the effect of
      acute administration of interferon on gastric myoelectrical activity (GMA) with
      the use of surface electrogastrography. METHODS: The study population comprised
      25 patients with chronic hepatitis C. All of them were naive to interferon. On 2
      days, after a 25-min basal GMA registration, in group A (5 men, 7 women, aged
      44.3 +/- 2.8 years) placebo or 5 million i.u. recombinant interferon alpha-2b
      (IFNA) was administered s.c. and the GMA was recorded in the interdigestive state
      for two periods (2 h and 4 h), separated by a 15-min break. In group B (7 men, 6
      women, aged 44.7 +/- 3.9 years) placebo or 5 million i.u. IFNA was injected s.c.
      after the ingestion of a semiliquid test meal of 364 kcal. Subsequently, the
      postprandial GMA was recorded for two periods (2 h and 4 h), separated by a 15
      min break. RESULTS: A typical flu-like syndrome was observed in 91.7% of patients
      in group A, and in 92.3% of patients in group B, thus providing evidence of the
      pharmacodynamic efficiency of the IFNA administration. In the fasted state, IFNA
      brought about a negligible increase in the rhythmicity and power of the gastric
      slow waves. IFNA did not elicit any statistically significant effect on gastric
      slow-wave activity postprandially. CONCLUSIONS: Acute administration of
      interferon does not involve any deterioration of GMA that could be linked to the
      previously reported upper abdominal symptoms in patients undergoing treatment
      with this drug.

PMID- 15580396
TI  - Comparison between the 13C-urea breath test and stool antigen test for the
      diagnosis of childhood Helicobacter pylori infection.
AB  - BACKGROUND: As noninvasive tests for Helicobacter pylori infection, the 13C-urea
      breath test (UBT) and stool antigen test have been widely used. In children,
      however, there are few studies reporting which test shows superior performance.
      The purpose of this study was to compare the 13C-UBT and stool antigen test for
      their accuracy in diagnosing H. pylori infection in children. METHODS: A total of
      123 Japanese children, ages 2 to 17 years (mean, 12 years) who underwent gastric
      biopsies for H. pylori infection were studied. The diagnoses included gastritis
      (n = 55), gastric ulcer (n = 5), duodenal ulcer (n = 20), iron-deficiency anemia
      (n = 7), and other conditions (n = 36). The cutoff value of the 13C-UBT was
      defined to be 3.5 per thousand. The stool antigen test was performed using the
      HpSA enzyme-linked immunosorbent assay (ELISA) (Premier Platinum HpSA). In 16
      patients who received eradication therapy, the 13C-UBT and HpSA were repeated 2
      months after treatment. RESULTS: Based on biopsy tests, 60 children were infected
      with H. pylori and 63 children were not. For the 13C-UBT, the sensitivity,
      specificity, and accuracy were 95.0% (95% confidence interval [CI], 86.1%-99.0%),
      98.4% (95% CI, 91.5%-100%), and 96.4% (95% CI, 93.6%-99.9%), respectively. For
      the HpSA, the sensitivity, specificity, and accuracy were 98.3% (95% CI, 90.8%
      100%), 98.4% (95% CI, 91.2%-100%), and 98.3% (95% CI, 96.0%-100%), respectively.
      There were no significant differences between the performance of these two tests.
      In the assessment of H. pylori eradication, the results of 13C-UBT and HpSA
      agreed with those of biopsy tests. CONCLUSIONS: The 13C-UBT and the HpSA are
      equally accurate for the diagnosis of active H. pylori infection in Japanese
      children.

PMID- 15580397
TI  - Second-line treatment for Helicobacter pylori infection in Japan: proton pump
      inhibitor-based amoxicillin and metronidazole regimen.
AB  - BACKGROUND: Recent studies have reported that proton pump inhibitor
      (PPI)/amoxicillin (A) metronidazole (M) therapy for Helicobacter pylori infection
      provides a sufficient cure rate in Japan in patients who have failed first-line
      treatment with PPI/amoxicillin and clarithromycin (AC). To validate the efficacy
      of this regimen as second-line therapy, our experience with second-line treatment
      using a PPI/AM regimen was reviewed. METHODS: We analyzed data on 151 patients
      who had been prescribed a 10-day PPI/AM re-treatment regimen after eradication
      failure of 1 to 2 weeks' first-line PPI/AC therapy. The PPI/AM regimen was given
      according to results of susceptibility testing (S+) in 31 patients. The group
      that had undergone susceptibility testing was further divided into two subgroups
      according to dosage: standard dose of omeprazole (O)/AM (n = 11) and double dose
      of lansoprazole (L)/AM (n = 20). The PPI/AM regimen was given without
      susceptibility testing (S-) to 120 patients. These patients were also divided
      into two subgroups according to whether they received omeprazole or lansoprazole:
      OAM (n = 61) and LAM (n = 59). Cure rates and adverse effects in each group were
      analyzed. RESULTS: The intention-to-treat (ITT)-based cure rate with/without
      susceptibility testing was 93.5% (95% confidence interval [CI], 79%-99%) and
      87.5% (95% CI, 80%-93%), respectively (not significant [NS]). The ITT-based cure
      rate in S+/S- for OAM and S+/S- for LAM was 90.9% (95% CI, 59%-100%)/82% (95% CI,
      70%-91%), and 95% (95% CI, 75%-100%)/93.2% (95% CI, 84%-98%), respectively (NS).
      Adverse effects were seen in 26.3% and 32.5% of patients in the OAM group and the
      LAM group, respectively (NS). CONCLUSIONS: The 10-day PPI/AM re-treatment regimen
      is safe and effective, suggesting its usefulness as second-line treatment in
      Japan in patients who have failed initial treatment with the PPI/AC regimen.

PMID- 15580398
TI  - Venous congestion induces mucosal apoptosis via tumor necrosis factor-alpha
      mediated cell death in the rat small intestine.
AB  - BACKGROUND: Tissue and organic venous congestion is a common pathophysiologic
      phenomenon. However, it is unclear whether venous congestion induces small
      intestinal mucosal apoptosis. The aim of this study was to investigate whether
      venous congestion, or congestion followed by re-outflow, induced small-intestinal
      mucosal apoptosis, and whether tumor necrosis factor-alpha is involved in this
      apoptosis. METHODS: Small-intestinal venous congestion was induced in rats by
      occlusion of the superior mesenteric vein with a micro-bulldog clamp. At the end
      of the congestive period, the clamp was released to facilitate congestion
      followed by re-outflow. The rats were injected with a neutral anti-tumor necrosis
      factor-alpha antibody (0.15 mg/kg) via the jugular vein for 30 min before venous
      congestion or congestion followed by re-outflow. Intestinal mucosal apoptosis was
      evaluated and tumor necrosis factor-alpha was assayed. The amounts of caspase-8,
      caspase-3, and cytochrome c were determined by Western blot analysis. RESULTS:
      Our results showed that venous congestion and congestion followed by re-outflow
      significantly increased mucosal apoptosis, the amount of mucosal tumor necrosis
      factor-alpha, and the levels of caspase-8 cleavage and caspase-3 activation, but
      did not induce cytochrome c release from mitochondria to the cytosol.
      Pretreatment with an anti-tumor necrosis factor-alpha antibody significantly
      reduced mucosal apoptosis after intestinal congestion or congestion followed by
      re-outflow. CONCLUSIONS: The present results support the view that venous
      congestion and congestion followed by re-outflow induce mucosal apoptosis in the
      rat small intestine, and show that the apoptosis occurs partly via tumor necrosis
      factor-alpha-mediated cell death.

PMID- 15580399
TI  - Correlation between clinical characteristics and mitochondrial D-loop DNA
      mutations in hepatocellular carcinoma.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) mutations are found in many kinds of human
      cancer. The aim of this study was to evaluate the relationship between mtDNA
      mutations in the liver and human hepatocarcinogenesis. METHODS: Direct sequencing
      of mtDNA was done in 54 hepatocellular carcinomas (HCCs) and 47 surrounding liver
      tissue samples, obtained from 54 patients with HCC, and in 5 liver samples
      without inflammation, obtained from 5 patients with metastatic liver tumors. We
      also examined p53 mutations in the 54 HCCs to examine the correlation between
      nuclear DNA mutations and mtDNA mutations. RESULTS: Mutations of mtDNA in the D
      loop region were found in both HCC and noncancerous liver tissue. In normal liver
      without chronic inflammation, no mtDNA mutation was detected. In every case, the
      number of mtDNA mutations in HCC correlated with that in noncancerous liver
      tissue. Twelve of 52 mutation sites in the D-loop region of mtDNA were specific
      for HCC. The mean number of mtDNA mutations was 1.7 in well-differentiated HCC,
      as compared with 4.5 in moderately differentiated HCC and 4.6 in poorly
      differentiated HCC. The frequency of mtDNA mutations was thus higher in less
      differentiated HCC. We detected p53 mutations in 15 (28%) of 54 HCCs. The mean
      number of mtDNA mutations was 5.3 in HCC with p53 mutations and 3.8 in HCC with
      wild-type p53 (P = 0.024). CONCLUSIONS: A higher frequency of mtDNA mutations was
      found in less differentiated HCCs, and it is also possible that mtDNA mutations
      are related to nuclear DNA mutations in HCC. The accumulation of mtDNA mutations
      is a useful predictor of hepatocarcinogenesis.

PMID- 15580400
TI  - Interferon therapy for aged patients with chronic hepatitis C: improved survival
      in patients exhibiting a biochemical response.
AB  - BACKGROUND: In Japan, generally, patients with chronic hepatitis C are aged. The
      aim of this study was to investigate the effect of interferon (IFN) therapy on
      the mortality of chronic hepatitis C patients over age 60. METHODS: Seven-hundred
      and seven patients with histologically proven chronic hepatitis C were enrolled
      in this study; 649 received IFN therapy (IFN group) and 58 did not (control
      group). The standardized mortality ratio (SMR) and Cox proportional hazard
      regression analysis were used to evaluate the effect of IFN on the survival of
      the patients. RESULTS: Mean follow-up periods in the IFN and control groups were
      5.7 and 6.7 years, respectively. During follow-up, 13 patients in the control
      group died (7 of liver-related diseases) and 42 in the IFN group died (29 of
      liver-related diseases). The SMRs of the control and IFN groups were 1.40 (95%
      confidence interval [CI], 0.76-2.45) and 0.73 (95% CI, 0.52-0.98) for overall
      death, and 10.70 (95% CI, 4.29-22.05) and 5.05 (95% CI, 3.38-7.26) for liver
      related death, respectively. Sustained and transient biochemical responders in
      the IFN group (SMR, 0.53; 95% CI, 0.01-2.97 and SMR, 3.25; 95% CI, 0.87-8.32,
      respectively) showed lower liver-related mortality compared with the control
      group. In patients with sustained virological response, liver-related mortality
      was also very low (SMR, 0.65; 95% CI, 0.01-3.61). The risk for liver-related
      death of sustained and transient biochemical responders was also low compared
      with that of the control group (adjusted risk ratios 0.10 [95% CI, 0.01-0.95] and
      0.50 [95% CI, 0.11-2.21], respectively). CONCLUSIONS: These results suggest that
      IFN treatment could reduce liver-related mortality in chronic hepatitis C
      patients over age 60, notably in patients showing a biochemical response and in
      those showing a sustained virological response.

PMID- 15580401
TI  - Efficacy of lamivudine treatment in Japanese patients with hepatitis B virus
      related cirrhosis.
AB  - BACKGROUND: Several clinical trials have suggested that lamivudine therapy is
      effective in patients with hepatitis B virus (HBV)-related cirrhosis. However,
      there are few studies of lamivudine therapy in Japanese patients with HBV
      cirrhosis. The aim of this study was to evaluate the efficacy of lamivudine
      therapy in Japanese patients with cirrhosis, and to evaluate the clinical course
      after the emergence of YMDD mutants. METHODS: Fifty-four consecutive adult
      Japanese patients with HBV-related cirrhosis were enrolled and continuously
      treated with lamivudine, daily for 6-35 months (median, 25 months). Twelve of the
      54 patients were hepatitis B envelope antigen (HBeAg)-positive. The clinical
      courses of 21 of the patients were evaluated using the Child-Pugh-Turcott (CPT)
      score. RESULTS: Lamivudine suppressed serum HBV-DNA to undetectable levels (<3.7
      LGE/ml) in 77.8% of patients at 12 months and in 61.3% at 24 months. Before the
      emergence of YMDD mutants, clinical improvement, defined as a decrease in the CPT
      score of 2 points or more, was apparent in 6 of 21 (29%) patients. No change in
      CPT score was evident in 14 of 21 patients (67%). YMDD mutants emerged in 19 of
      54 (35%) patients. The cumulative emergence rates increased each year. The
      emergence rate of YMDD mutants in patients with HBV cirrhosis was higher than
      that in patients with chronic hepatitis. After the emergence of YMDD mutants, 3
      of 12 (25%) patients with YMDD mutants showed CPT score increases of 2 points or
      more. CONCLUSIONS: Lamivudine therapy improved the clinical course in some
      cirrhotic patients. However, in patients with Child's B and C cirrhosis, the
      emergence of YMDD mutants sometimes led to deterioration of liver function.

PMID- 15580402
TI  - Earlier recurrence of esophageal varices, following therapy, in patients with
      primary biliary cirrhosis (PBC) compared with non-PBC patients.
AB  - BACKGROUND: Variceal bleeding is a common, life-threatening complication of
      primary biliary cirrhosis (PBC). Recently, several reports have suggested that
      the existence of esophageal varices in patients with PBC is a significant factor
      in the assessment of disease prognosis. However, there have been no reports on
      the recurrence of esophageal varices following treatment in patients with PBC. In
      this study, we investigated the recurrence of esophageal varices in PBC patients
      and attempted to identify predictive factors for the recurrence of esophageal
      varices. METHODS: Between April 1993 and August 2003, 138 patients with
      esophageal varices who had been treated by endoscopic variceal ligation (EVL; 96
      men and 42 women; age, 33-83 years; mean, 62.6 +/- 10.1 years), were enrolled in
      the present study. The diagnosis of esophageal varices was made by upper
      gastrointestinal endoscopy, and the varices were graded according to the criteria
      of the Japanese Research Society for Portal Hypertension. The relationship
      between the recurrence of esophageal varices and factors such as biochemical and
      hematological parameters, as well as the etiology of the liver disease, was
      analyzed using the Kaplan-Meier method and the multivariate Weibull regression
      model. RESULTS: PBC patients had an earlier recurrence of esophageal varices
      compared to non-PBC patients, and two factors, prothrombin time and etiology
      (PBC/non-PBC), were indicative of significantly earlier recurrence of esophageal
      varices. CONCLUSIONS: We should be extra careful in the follow-up of patients
      with PBC after therapy for esophageal varices.

PMID- 15580403
TI  - Adequate timing of ribavirin reduction in patients with hemolysis during
      combination therapy of interferon and ribavirin for chronic hepatitis C.
AB  - BACKGROUND: Hemolytic anemia is one of the major adverse events of the
      combination therapy of interferon and ribavirin. Because of ribavirin-related
      hemolytic anemia, dose reduction is a common event in this therapy. In this
      clinical retrospective cohort study we have examined the suitable timing of
      ribavirin reduction in patients with hemolysis during combination therapy.
      METHODS: Thirty-seven of 160 patients who had HCV-genotype 1b, had high virus
      load, and received 24-week combination therapy developed anemia with hemoglobin
      level <10 g/dl or anemia-related signs during therapy. After that, these 37
      patients were reduced one tablet of ribavirin (200 mg) per day. After reduction
      of ribavirin, 27 of 37 patients could continue combination therapy for a total of
      24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could
      not continue combination therapy because their <8.5 g/dl hemoglobin values
      decreased to or anemia-related severe side effects occurred (group B). We
      assessed the final efficacy and safety after reduction of ribavirin in groups A
      and B. RESULTS: A sustained virological response (SVR) was 29.6% (8/27) in group
      A and 10% (1/10) in group B, respectively. A 34.4% (12/27) of SVR + biological
      response in group A was higher than 10% (1/10) in group B ( P = 0.051), with
      slight significance. With respect to hemoglobin level at the time of ribavirin
      reduction, a rate of continuation of therapy in patients with > or =10 g/dl
      hemoglobin was higher than that in patients with <10 g/dl ( P = 0.036).
      CONCLUSIONS: Reduction of ribavirin at hemoglobin level > or =10 g/dl is suitable
      in terms of efficacy and side effects.

PMID- 15580404
TI  - Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a
      preliminary study.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a new palliative option in patients
      with non-resectable bile duct carcinoma (BDC). Here, we assessed the efficacy of
      adjuvant photodynamic therapy in eight patients with BDC who underwent surgical
      resection. METHODS: Five patients had extrahepatic BDC, two had intrahepatic
      cholangiocarcinoma, and one had ampullary carcinoma. Cancer cells were
      microscopically detected in the stump of the hepatic duct in six patients, and
      biliary stenosis caused by remnant tumor was observed in one patient. One patient
      had tumor recurrence with occlusion of the bile duct. At 48 h prior to PDT,
      porfimer sodium was injected intravenously. A pulse laser by an eximer dye laser
      (50-100 J/cm2) with a wavelength of 630 microm was applied through an endoscope
      to the hepatic stump or tumor lesion. RESULTS: Marked destruction of the tumor
      and ductal epithelium was observed on day 1 after PDT. After PDT, four patients
      developed mild dermatitis, but no severe morbidity or mortality was noted. In
      patients who underwent PDT for the stump, one patient showed distant metastasis
      at 31 months, and four patients did not show tumor recurrence at 17, 12, 12, and
      6 months, respectively. However, one of the eight patients died at 2 months, of
      an unrelated cause. In two patients with occlusion caused by tumor growth,
      resolution of bile duct stenosis was noted on day 7. These patients showed re
      occlusion by tumor at 20 and 8 months. CONCLUSIONS: Adjuvant PDT is a safe and
      useful option for a better survival benefit in patients with BDC undergoing
      surgical resection.

PMID- 15580405
TI  - Nonalcoholic steatohepatitis associated with psoriasis vulgaris.
AB  - A 24-year-old man was admitted to our hospital because of liver dysfunction. He
      had been diagnosed as having psoriasis vulgaris at 18 years of age. Physical
      examination demonstrated obesity, general erythema, and hepatomegaly. Laboratory
      data revealed elevated serum levels of aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, and glucose. A histological examination
      of the liver revealed macrovesicular fatty change and infiltration of
      inflammatory cells, including lymphocytes and polymorphonuclear cells, within the
      liver lobules. Pericentral fibrosis and pericellular fibrosis were also
      recognized. He was diagnosed as having nonalcoholic steatohepatitis (NASH), based
      on the fact that he had no habit of drinking alcohol, as well as psoriasis
      vulgaris and diabetes mellitus. We herein report a very rare case of NASH
      associated with psoriasis vulgaris.

PMID- 15580406
TI  - Vogt-Koyanagi-Harada disease occurring during interferon alpha therapy for
      chronic hepatitis C.
AB  - Retinal abnormalities, including retinal hemorrhage and "cotton-wool" spots,
      often occur within the first 8 weeks in the course of interferon therapy in
      patients with chronic hepatitis C. Here, we describe a case of Vogt-Koyanagi
      Harada disease occurring 4 months after the start of interferon alpha treatment,
      probably induced by the immunomodulatory effects of interferon. Therefore, we
      conclude that chronic hepatitis C patients, especially people with darkly
      pigmented skin, need to be closely monitored for ophthalmologic complications, by
      periodic check-up of the optic fundi, for a prolonged period, during interferon
      treatment.

PMID- 15580407
TI  - Obstructive jaundice caused by enteropathy-associated T-cell lymphoma in a
      patient with celiac sprue.
AB  - Patients with celiac sprue carry a considerable risk of gastrointestinal
      malignancies; in particular, non-Hodgkin's lymphoma. These malignancies represent
      the most serious complications of celiac disease. Commonly, patients present with
      deteriorating symptoms of the underlying disease, which makes an early diagnosis
      difficult. We report a patient with a 13-year history of celiac sprue presenting
      with painless jaundice and a Courvoisier gallbladder. Abdominal computed
      tomography (CT) scan showed thickening of the duodenal wall, suggesting a
      neoplastic infiltration of the papilla of Vater, causing biliary obstruction.
      Biopsies taken on endoscopy revealed enteropathy-associated T-cell lymphoma of
      the duodenum. Biliary obstruction is a rare clinical finding in enteropathy
      associated T-cell lymphoma. To our knowledge, this is the first reported case of
      this unusual manifestation in celiac disease.

PMID- 15580408
TI  - Pneumocystis carinii pneumonia in patients with ulcerative colitis.

PMID- 15580409
TI  - A pregnant patient with fulminant hepatic failure was found to carry a novel
      missense mutation in the argininosuccinate synthetase gene.

PMID- 15580410
TI  - Chronic diarrhea and protein-losing gastroenteropathy caused by Dientamoeba
      fragilis.

PMID- 15580411
TI  - The role of TNF-alpha in ischemic disease of mesenteric venous systems.

PMID- 15580412
TI  - Efficacy of interferon therapy for aged patients with chronic hepatitis C.

PMID- 15580413
TI  - How to avoid discontinuation of ribavirin in combination with interferon to
      maintain efficacy of treatment for chronic hepatitis C patients.

PMID- 15580414
TI  - Further characterization of the supine empty stress test for predicting low
      valsalva leak point pressures.
AB  - The aim of this study is to determine if the diagnostic accuracy of the supine
      empty stress test (SEST) differs depending on the volume of residual urine. We
      performed a review of all patients who were diagnosed with stress urinary
      incontinence (SUI) via multi-channel urodynamics including valsalva leak point
      determinations (VLPP). A SEST was performed and the residual urine recorded via
      catheterization. The test-specific indices of the SEST for the prediction of low
      VLPP (defined as <60 cm H(2)0) were determined for varying residual volumes.
      Ninety-nine patients were included. Regardless of residual volume, low
      sensitivities, specificities and positive predictive values were demonstrated.
      Sensitivity and positive predictive values were further reduced and negative
      predictive values were improved slightly with higher residual volume. The highest
      negative predictive value was 89% at a residual volume of greater than 10 mL.
      Residual urine volume has minimal impact on the utility of the SEST.

PMID- 15580415
TI  - Non-pregnant patients' preference for delivery route.
AB  - The objective of the study was to survey non-pregnant women regarding their
      preference for obstetric delivery route and to assess their awareness of the
      maternal and fetal risks of obstetric delivery. We wished to determine the
      percentage of non-pregnant women who would choose elective cesarean section and
      to correlate demographic factors. We compared women who elected cesarean delivery
      versus vaginal delivery. All patients presenting for routine gynecologic care
      were asked to complete an anonymous survey. Demographic variables analyzed were
      patient age, race, employment, insurance type and household income. Secondary
      data regarding knowledge of the risks and benefits of cesarean and vaginal
      delivery were assessed with a Likert Scale. Of patients surveyed, 13.3% preferred
      cesarean section. The only significant demographic factor was was race, with
      21.7% of non-whites and 7.8% of whites choosing cesarean section. Most patients
      agreed that elective cesarean sections should be performed and reimbursed by
      insurance. The majority of women answered neutral regarding the maternal and
      neonatal risks of obstetrical delivery. The unique feature of this observational
      study is the sole participation of non-pregnant patients. The percentage of women
      who would elect cesarean section has significant public health implications. The
      only difference noted between demographic groups is that non-white women had a
      stronger preference for cesarean. Without counseling, most women are unsure of
      the risks of delivery route on maternal and neonatal health.

PMID- 15580416
TI  - Infected abdominal sacrocolpopexies: diagnosis and treatment.
AB  - The abdominal sacrocolpopexy is an excellent procedure to surgically treat
      vaginal vault prolapse. A synthetic graft is often used to support the vaginal
      apex, but has the potential to become infected or erode, requiring its removal or
      revision. The purpose of this paper is to report our experience in the management
      of patients with infected synthetic grafts after abdominal sacrocolpopexy. A
      review of the patient databases from three specialty gynecology centers was
      performed from March 1996 to June 2002. Only patients with an infected graft
      after an abdominal sacrocolpopexy were included in the study; patients with
      either suture or graft erosion responding to conservative treatment were
      excluded. Twenty-two women, ages 37-73 years, developed infection of the
      synthetic graft after an abdominal sacrocolpopexy (1-60 months after their
      initial surgery, mean 8.8 months). The infected materials included
      polytetrafluoroethylene (PTFE, Goretex, n =15) and polypropylene (n=7). Nine of
      the 15 PTFE meshes and four of the seven polypropylene meshes were placed at the
      time of a contaminated case (abdominal hysterectomy [n=12], colon resection
      [n=1]). Eighteen (82%) of the infected grafts involved braided permanent suture
      to attach the graft to the vaginal wall, monofilament/non-braided permanent
      suture was used in three patients, and suture type could not be determined in
      one. All graft removals were attempted vaginally, and this was successful in 16
      cases (73%). Two patients experienced significant bleeding: the first patient
      required an emergency laparotomy and the second patient's bleeding was controlled
      with packing. A rectovaginal fistula occurred 3 weeks postoperatively in one
      patient. Synthetic graft infection should be considered as the differential
      diagnosis in a patient who has undergone an abdominal sacrocolpopexy.
      Transvaginal removal is preferred, but is fraught with potentially serious
      complications. The use of braided permanent sutures to affix the graft to the
      vagina may be associated with mesh infections.

PMID- 15580417
TI  - Is the pelvic organ prolapse quantification system (POPQ) being used? A survey of
      members of the International Continence Society (ICS) and the American
      Urogynecologic Society (AUGS).
AB  - The authors performed a web-based questionnaire survey of 667 members of the ICS
      and AUGS to determine the current use of the pelvic organ prolapse quantification
      (POPQ) system by members of the professional societies which have advocated its
      use. Three hundred and eighty (57%) gynecologists responded. This international
      survey shows that only 40.2% of ICS and AUGS members who responded routinely use
      the POPQ system in their clinical practice and provides information on the most
      common reasons for not using it. The results highlight some of the concerns
      regarding the complex nature of the system and its acceptance and use by
      specialists worldwide. It also suggests the need for a simplified version of the
      classification system that is user-friendly and can be adopted by all
      practitioners.

PMID- 15580418
TI  - Tension free vaginal tape: is the intra-operative cough test necessary?
AB  - The tension-free vaginal tape (TVT) procedure is recognised as an effective
      treatment for genuine stress incontinence. It was first described using local
      anaesthesia, with an intra-operative cough test helping to correctly position the
      tape. Many patients prefer general anaesthesia and often, patients with genuine
      stress incontinence do not leak when supine. This aim of this study was to
      compare the outcome in TVTs performed under general anaesthesia with those
      performed under spinal anaesthesia. Retrospective analysis of 105 patients, all
      of whom had urodynamically proven genuine stress incontinence and underwent TVT
      procedure, was performed: 52 under spinal anaesthesia and 53 under general
      anaesthesia. The primary and secondary outcome measures were the success or
      failure of the procedure and the complication rate, respectively. There was no
      significant difference in outcome or complication rate between the two groups.
      The type of anaesthetic used does not influence the outcome and we question the
      necessity of an intra-operative cough test.

PMID- 15580419
TI  - Urogynecology experience in Canada's obstetrics and gynecology residency
      programs.
AB  - This study aimed to evaluate the exposure of obstetrics and gynecology residents
      to urogynecologic training and to compare this to the program directors'
      expectations. A cross-sectional questionnaire study was performed surveying the
      60 final-year residents and their program directors at all 16 Canadian residency
      programs. Questions covered areas of knowledge and skills in basic and advanced
      urogynecology. Thirty-two (53%) residents and nine (56%) program directors
      responded. Twenty-six (81%) residents had a formal urogynecology rotation with
      training in incontinence, prolapse, pessary-fitting, and urodynamics. Residents
      performed a median of: 50 vaginal hysterectomies, 30 anterior repairs, 30
      posterior repairs, 35 retropubic urethropexies, and 15 cystoscopies. All other
      procedures had a median of 6 or less. Responses of residents and program
      directors correlated well. Although residents in Canada have adequate exposure to
      simple urogynecologic procedures, they perform few complex cases. Such procedures
      should be performed by physicians with additional urogynecology fellowship
      training.

PMID- 15580420
TI  - The open bladder neck: a significant finding?
AB  - Women with lower urinary tract symptoms were retrospectively studied. They were
      all investigated using a urinary symptoms questionnaire, a frequency-volume chart
      and videocystourethrography. An open bladder neck was recorded at maximum
      cystometric capacity with the patient standing in the left lateral position, if
      contrast medium entered the proximal urethra at rest in the absence of a detrusor
      contraction or an increase in intra-abdominal pressure. Women with neurological
      disorders were excluded. Of 4500 women, 2,593 (57.6%) had a single urodynamics
      diagnosis and were included in the study: 1207 (46.5%) had urodynamics diagnosis
      of urodynamic stress incontinence, 558 (21.5%) had detrusor overactivity, 118
      (4.6%) had sensory urgency, and 710 (27.4%) had a normal urodynamic study. Out of
      the 2,593 women included, 776 women (29.9%) had an open bladder neck at rest
      while 1817 (70.1%) had a closed bladder neck at rest. Only 45% (542/1207) of
      women with urodynamic stress incontinence had an open bladder neck at rest.
      Seventy percent (542/776) of women with an open bladder neck had a diagnosis of
      urodynamic stress incontinence whilst 73% of women with detrusor overactivity and
      93% of those with sensory urgency had a closed bladder neck. An open bladder neck
      at rest is not diagnostic of urethral sphincter incompetence but is associated
      with urodynamic stress incontinence. It is not associated with urgency as few
      women with sensory urgency and detrusor overactivity were found to have an open
      bladder neck. Imaging the bladder neck at rest has questionable value.

PMID- 15580421
TI  - Estrogen receptor in pelvic floor tissues in patients with stress urinary
      incontinence.
AB  - Our study is to investigate the presence of estrogen receptor (ER) and its
      possible etiological relationship with the development of stress urinary
      incontinence (SUI). Thirty-one biopsy specimens from pelvic floor tissues were
      obtained from 31 patients categorized into three groups: pelvic organ prolapse
      (POP), SUI and control groups. ER in the pelvic muscles tissues was evaluated
      quantitatively after immunohistochemical staining to visualize the ER in the
      tissue. The sampling rate of levator ani (striated) muscle was 6.7% in total
      sample from the pelvic floor tissues, with the remaining showing connective
      tissues, smooth muscles and nerve fibers. ER positive staining was found in the
      in the nuclei of connective tissue, smooth muscles and nerve fibers. The positive
      rates of ER staining in tissues were 1.4%, 4.7% and 5.7%, respectively in control
      group versus 1.1%, 2.8% and 2.7% in SUI group and 4.1%, 9.5% and 11.6% in POP
      group. The positive rates of ER staining in connective tissue, smooth muscle and
      nerve fibers in SUI group were significantly lower than that in control and POP
      group (P<0.01). Our study suggests that a decrease of ER in the pelvic floor
      tissues might be related to the occurrence of SUI and implies that hormone
      replacement therapy might not be effective in treatment for SUI.

PMID- 15580422
TI  - The clinical and urodynamic effects of the tension free bladder neck sling
      procedure.
AB  - This study evaluated the clinical and urodynamic findings before and after
      tension-free bladder neck sling (TBS) procedure with Prolene tape. We enrolled 32
      women who underwent TBS for genuine stress incontinence without intrinsic
      sphincter deficiency or severe uterovaginal prolapse. All subjects received 1-h
      pad test, Q-tip test, multichannel urodynamic testing, introital ultrasonography,
      and the Bristol Female Lower Urinary Tract Symptoms Questionnaires before and 1
      year after surgery. Of the 32 subjects 27 were cured of stress incontinence, two
      improved, and three failed. The incidence of irritative symptoms and incomplete
      bladder emptying were significantly lower after surgery. The mean urethral
      straining angle showed a significant decrease from 73.8 degrees preoperatively to
      30.1 degrees postoperatively. At rest the postsurgical position of the bladder
      neck (BN) was localized more cranially. During straining both ventral and caudal
      mobility of the BN decreased significantly following TBS, causing a more cranial
      and dorsal position of the BN. Urodynamic parameters including functional
      urethral length, maximal urethral closure pressure, and pressure transmission
      ratio showed significant increases after surgery. TBS could decrease the
      hypermobility of the BN and restore the BN support to prevent urinary leakage
      during straining, instead of urethral obstruction. The subjective and objective
      cure rate of stress incontinence is 84%, similar to those results reported after
      retropubic urethropexy and tension-free vaginal tape procedure. It is also worth
      emphasizing that no postoperative urinary retention occurred, although the
      limited number of cases makes it hard to confirm the significance of findings
      over the retention rate of tension-free vaginal tape.

PMID- 15580423
TI  - Urethral erosion of tension-free vaginal tape presenting as recurrent stress
      urinary incontinence.
AB  - The suburethral sling with tension-free vaginal tape (TVT) has become a popular
      treatment for stress urinary incontinence. Erosion of the mesh into the urethra
      is rare, usually presenting with hematuria, pain, voiding dysfunction or urge
      incontinence. A patient with stress incontinence was treated with a TVT
      suburethral sling. One month later, symptoms of recurrent stress incontinence
      developed. Cystourethroscopy revealed urethral mesh erosion. Surgical removal
      involved cystourethroscopic-assisted transurethral resection of the mesh,
      followed by vaginal dissection and periurethral withdrawal. Urethral mesh erosion
      should be considered in a patient who presents with atypical symptoms after being
      treated with a suburethral sling. It is important to obtain a detailed history
      and have a high clinical index of suspicion for erosion. Careful and
      comprehensive urethroscopy, in addition to cystoscopy, should be a mandatory part
      of the TVT procedure. Further study is needed to determine the optimal technique
      for mesh removal.

PMID- 15580424
TI  - Postoperative ureteral obstruction after confirmed ureteral patency: a case
      report.
AB  - Ureteral injury after pelvic floor surgery and anti-incontinence surgery is a
      well-known risk. It is common practice to evaluate ureteral patency immediately
      after surgery prior to leaving the operating theater to assure that the ureters
      are open and functional. In this report we discuss the case of a patient who was
      admitted 9 days after surgery with acute onset of ureteral obstruction after
      having patent ureters documented at the time of surgery. A literature search
      failed to show any documented cases.

PMID- 15580425
TI  - Vesicocervical fistula: an unusual complication of vesicovaginal [corrected]
      fistula repair.
AB  - A rare case of vesicocervical fistula following repair of a vesicovaginal fistula
      is presented. The patient complained of cyclical menouria since the first repair
      done 15 years ago and gradually worsening urinary incontinence. A laparoscopic
      assisted repair of the fistula was performed and the patient is fully continent
      at 12-months follow up.

PMID- 15580426
TI  - Transurethral resection of transvaginal tape.
AB  - Urethral erosion is an uncommon complication after tension-free vaginal tape
      (TVT) procedure. However, management is a challenge and morbidity significant
      because of the necessity to incise the urethra to gain access to the material.
      This is a report of a case of transurethral resection of such mesh. A 77-year-old
      women presented at 7 months postoperatively with complaints of incomplete
      emptying and persistent incontinence. Urodynamic testing and cystoscopy revealed
      intrinsic sphincter deficiency, an elevated post void residual and erosion of the
      TVT tape into the urethral lumen. The tape was removed without any incisions via
      an operative cystoscope and hysteroscopic scissors. All urinary symptoms
      resolved. Partial urethral transection can be managed successfully with
      transurethral resection of the material. This diagnosis should be considered in
      patients with incomplete emptying and recurrent incontinence.

PMID- 15580428
TI  - [Which points deserve special attention in the new guidelines on X-ray use
      (testing guidelines for experts and quality assurance guidelines)?].
AB  - Two important guidelines for the application of X-rays in medicine became
      effective on 1 October 2003 and 1 December 2003. These are testing guidelines for
      experts and quality assurance guidelines. Both guidelines are very extensive and
      not always easy to interpret. In the present paper the authors try to explain in
      detail some chapters important for radiology and to make the necessary technical
      background transparent. Both authors took an essential part in forming the
      guidelines.

PMID- 15580430
TI  - Necrotizing fasciitis after liposculpture.

PMID- 15580431
TI  - Complications with the use of botulinum toxin type a in facial rejuvenation:
      report of 8 cases.
AB  - The botulinum toxin A is produced by Clostridium botulinum and causes a
      reversible, selective muscle relaxation that leads to a temporary flattening of
      the mechanical component of wrinkling without the stigmata of invasive surgery.
      Since the end of the 1980s, this neurotoxin has been used to treat mimic facial
      lines with good results. Although this is considered a safe therapy, with adverse
      effects typically self-limited, more severe complications have been observed when
      it is used by nonskilled physicians or in improper dosages. This article reports
      eight patients treated with botulinum toxin A for aesthetic purposes who
      developed different complications. Treatment of the complication included the use
      of electrical stimulation, lymphatic drainage, antiinflammatory therapy,
      dipivefrine cloridrate drops, and other approaches. With specific treatment for
      each patient, the lengths of these complications seemed to be reduced.

PMID- 15580432
TI  - Nasal tip plasty using various techniques in rhinoplasty.
AB  - Rhinoplasty is one of the most common aesthetic surgical procedures in Korea
      today. However, simple augmentation rhinoplasty results often failed to satisfy
      the high expectations of patients. As a result, many procedures have been
      developed to improve the appearance of the nasal tip and nasal projection.
      However, the characteristics of Korean nasal tips including the bulbous
      appearance (attributable to the thickness of the skin), flared nostrils, and
      restriction of the nasal tip attributable to an underdeveloped medical crus of
      the alar cartilage and a short columella have made such procedures difficult.
      Currently, most plastic surgeons perform rhinoplasty simultaneously with various
      nasal tip plasty techniques to improve the surgical results. An important part of
      an aesthetically pleasing result is to ensure an adequate nasal tip positioned
      slightly higher than the proper dorsum, with the two tip defining points in close
      proximity to each other, giving the nose a triangular shape from the caudal view.
      From June 2002 to November 2003, the authors performed rhinoplasty with
      simultaneous nasal tip plasty using various techniques according to the tip
      status of 55 patients (25 deviated noses, 9 broad noses, 15 low noses, and 6
      secondary cleft lip and nose deformities). The surgery included realignment of
      alar cartilage by resection and suture, fibroareolar and subcutaneous tissue
      resection, tip graft, and columellar strut. The postoperative results over an
      average period of 10 months were entirely satisfactory. There were no patient
      complaints, nor complications resulting from the procedures. Good nasal tip
      projection, natural columellar appearance, and improvement of the nasolabial
      angle were achieved for most patients. In conclusion, rhinoplasty with
      simultaneous nasal tip plasty, achieved by a variety of techniques according to
      patients' tip status, is an effective method for improving the appearance of the
      nose and satisfying the desires of the patients.

PMID- 15580433
TI  - Midface volume replacement with a transmaxillary implant.
AB  - BACKGROUND: Volume replacement is an essential component of midface rejuvenation.
      Previously designed alloplastic implants augment bony prominences. The Maxout
      implant was configured to add height to the lowest surface, the canine fossa.
      METHODS: A random series of patients, from an office-based practice requested
      midface augmentation. Three of these patients were human immunodeficiency virus
      (HIV) positive. With the patient under local anesthetic, bilateral Maxout
      implants were inserted through either an intraoral or an intranasal incision.
      RESULTS: All the implants produced a satisfactory aesthetic improvement. In one
      HIV-positive patient, one implant placed intraorally became infected and required
      removal. It was replaced 3 months later through the transnasal approach. All the
      patients had retained their implants 1 year later. CONCLUSIONS: The Maxout
      implant is easy to insert and remove, aesthetically effective, secured by bone
      structures, and located in a neutral position. The risk of infection must be
      considered, especially for HIV-positive patients.

PMID- 15580437
TI  - Psychometric documentation of a quality-of-life questionnaire for patients
      undergoing antireflux surgery (QOLARS).
AB  - BACKGROUND: The purpose of our study was to develop a quality-of-life (QoL)
      questionnaire for patients with gastroesophageal reflux disease (GERD) who have
      undergone laparoscopic fundoplication. This questionnaire was developed to be
      more comprehensive than existing measures. METHODS: Between 1994 and 2002, 252
      patients underwent laparoscopic fundoplication for GERD in the 1st Department of
      Surgery, Semmelweis University. We undertook a retrospective analysis: each of
      252 operated patients was given a questionnaire and was requested to complete it
      and return it in an enclosed envelope. A total of 116 patients returned completed
      questionnaires. The patients included 55 men and 61 women, with a mean age of 46
      years (range 14-77). These patients were used in the psychometric evaluation. The
      questionnaire consisted of 50 questions (including the Visick score, EORTC-QLQ
      C30, and a modified GERD-HRQL). RESULTS: Internal consistency reliability was
      high (alpha value overall, 0.95, range, 0.74-0.96). Using convergent and
      divergent validity, construct validity was evaluated by examining Pearson
      correlation coefficients between items and scales. Construct validity was
      demonstrated based on observed correlations. Known groups validity was upheld
      because patients who experienced more symptoms and patients who has higher Visick
      scores reported worse QoL than those with less symptoms or lower Visick scores.
      CONCLUSIONS: Our questionnaire is a short and user-friendly instrument with
      excellent psychometric properties. It has been found to be valid and reliable.

PMID- 15580438
TI  - Acute tensile strength analysis of collagen solder for mesh fixation to the
      peritoneal surface.
AB  - BACKGROUND: In this study, we assessed the feasibility of laser-assisted tissue
      welding as a means of fixing mesh prostheses to the peritoneum. We then tested
      the initial tensile strength of the bonds. METHODS: Fresh porcine peritoneal
      coupons were lap-joint bonded with laser-activated solder. Anesthetized New
      Zealand white rabbits and Yorkshire pigs also underwent laparotomy. Vicryl mesh
      (2.0 x 1.0 cm) was attached to the peritoneum using a laser system (1.43 mu, 2.5
      W, 60 degrees C), solder formulations and configurations, and a 1 cm2 bond area.
      Control segments were affixed with 4.8-mm staples. After the animals were killed,
      the segments were excised en bloc. Tensile strength assessment was conducted by
      measuring peak force breaking strength. RESULTS: The strength of the solder bonds
      were similar in all groups (range, 261.5 +/- 170.3-465.3 +/- 288.2 g/cm2) and
      were not statistically different from the controls (215.8 +/- 117.8 g/cm2).
      CONCLUSIONS: These values are similar to the 200-500 g/cm2 acute strengths
      reported for sutured or stapled peritoneal closure. Mesh fixation by solder is
      feasible, and further development of this technology is warranted.

PMID- 15580439
TI  - The susceptibility of prosthetic biomaterials to infection.
AB  - BACKGROUND: Despite the use of a sterile technique and the administration of
      prophylactic antibiotics during surgical procedures, mesh infection continues to
      complicate the use of biomaterials. The purpose of this study was to compare the
      susceptibility to infection of prosthetic biomaterials in a live-animal model.
      METHODS: The following seven prosthetic mesh biomaterials were used in this
      study. Expanded polytetrafluoroethylene (ePTFE) with silver/chlorhexidine (DM+),
      ePTFE (DM), porcine intestinal submucosa (S), polypropylene (M),
      ePTFE/polypropylene (X), hyaluronate/carboxymethylcellulose/polypropylene (SM),
      and human acellular dermal matrix (A). Lewis rats (n = 108) underwent creation of
      a single ventral hernia; 105 of them were repaired with a different mesh (2-cm2
      piece). Twelve pieces of each mesh were inoculated at the time of hernia repair
      with 10(8) Staphylococcus aureus (n = 84). Three pieces of each mesh were placed
      without bacterial inoculation (n = 21). In three animals, no mesh was placed;
      instead, the peritoneum of the hernia defect was inoculated (n = 3). After 5
      days, the animals were killed and the mesh was explanted (peritoneum for the
      nonmesh control). The mesh was vortex-washed and incubated in tryptic soy broth.
      Bacterial counts were determined using serial dilutions and spot plates and
      quantified in colony-forming units (CFU) per square centimeter of mesh present in
      the vortex wash fluid (wash count) and the soy broth (broth count). Data are
      presented as the mean log(10), with analysis of variance (ANOVA) and Tukey's test
      used to determine significance (p < 0.05). RESULTS: The DM+ material had no
      detectable live bacteria in the wash or broth counts in 10 of 12 tested samples
      (p = 0.05). Of the samples that showed bacterial growth, the peritoneum control
      group had a lower wash count than A (p = 0.05) and the lowest broth count of all
      the materials except for DM+ (p = 0.05). In addition, SM had a significantly
      lower wash count than A (p = 0.05), with no broth count difference. In regard to
      wash and broth counts, DM, M, X, SM, S, and A were no different (p = NS).
      CONCLUSIONS: The DM+ material was the least susceptible to infection.
      Impregnation with silver/chlorhexidine killed the inoculated bacteria, preventing
      their proliferation on the mesh surface. Other than DM+, native peritoneal tissue
      appears to be the least susceptible to infection. Silver/chlorhexidine appears to
      be an effective bactericidal agent for use with mesh biomaterials.

PMID- 15580436
TI  - Obesity surgery: evidence-based guidelines of the European Association for
      Endoscopic Surgery (EAES).
AB  - BACKGROUND: The increasing prevalence of morbid obesity together with the
      development of laparoscopic approaches has led to a steep rise in the number of
      bariatric operations. These guidelines intend to define the comparative
      effectiveness and surrounding circumstances of the various types of obesity
      surgery. METHODS: A consensus panel representing the fields of general/endoscopic
      surgery, nutrition and epidemiology convened to agree on specific questions in
      obesity surgery. Databases were systematically searched for clinical trial
      results in order to produce evidence-based recommendations. Following two days of
      discussion by the experts and a plenary discussion, the final statements were
      issued. RECOMMENDATIONS: After the patient's multidisciplinary evaluation,
      obesity surgery should be considered in adults with a documented BMI greater than
      or equal to 35 and related comorbidity, or a BMI of at least 40. In addition to
      standard laboratory testing, chest radiography, electrocardiography, spirometry,
      and abdominal ultrasonography, the preoperative evaluation of obesity surgery
      patients also includes upper gastrointestinal endoscopy or radiologic evaluation
      with a barium meal. Psychiatric consultation and polysomnography can safely be
      restricted to patients with clinical symptoms on preoperative screening.
      Adjustable gastric banding (GB), vertical banded gastroplasty (VBG), Roux-en-Y
      gastric bypass (RYGB) and biliopancreatic diversion (BPD) are all effective in
      the treatment of morbid obesity, but differ in degree of weight loss and range of
      complications. The choice of procedure therefore should be tailored to the
      individual situation. There is evidence that a laparoscopic approach is
      advantageous for LAGB, VBG, and GB (and probably also for BPD). Antibiotic and
      antithromboembolic prophylaxis should be used routinely. Patients should be seen
      3 to 8 times during the first postoperative year, 1 to 4 times during the second
      year and once or twice a year thereafter. Outcome assessment after surgery should
      include weight loss and maintainance, nutritional status, comorbidities and
      quality-of-life.

PMID- 15580440
TI  - The laparoscopic repair of suprapubic ventral hernias.
AB  - BACKGROUND: The complexity of dissection and the close proximity of the hernia to
      bony, vascular, nerve, and urinary structures make the laparoscopic repair of
      suprapubic hernias (LRSPH) a formidable operation. We performed a prospective
      evaluation of the outcomes of patients undergoing LRSPH. METHODS: The study
      population comprised 36 patients undergoing LRSPH from July 1996 to January 2004.
      Patient demographics, hernia sizes, mesh types and sizes, perioperative outcomes,
      and recurrences were documented. After our early experience with this operation,
      the repair evolved to include transabdominal suture fixation to the pubic bone,
      Cooper's ligament, and above the iliopubic tract. RESULTS: There were 26 women
      and 10 men. They had a mean age of 55.9 years (range, 33-76) and a mean body mass
      index (BMI) of 31.0 kg/m2 (range, 22-67). Twenty-two (61%) of the repairs were
      for recurrent hernias, with an average of 2.3 previously failed open repairs each
      (range, 1-11). The mean hernia size was 191.4 cm2 (range, 20-768), and the
      average mesh size was 481.4 cm2 (range, 193-1,428). All repairs were performed
      with expanded polytetrafluoroethylene (ePTFE) mesh. Mean operating time was 178.7
      min (range, 95-290). Mean blood loss was 40 cc (range, 20-100). One patient
      undergoing her fifth repair required conversion due to adhesions to a
      polypropylene mesh. Hospital stay averaged 2.4 days (range, 1-7). Mean follow-up
      was 21.1 months (range, 1-70). Complications (16.6%) included deep venous
      thrombosis (n = 1), prolonged pain for >6 weeks (n = 1), trocar site cellulitis
      (n = 1), ileus (n = 1), prolonged seroma (n = 1), and Clostridium difficile
      colitis (n = 1). Hernias recurred in two of our first nine patients, for an
      overall recurrence rate of 5.5%. Since we began using the technique of applying
      multiple sutures directly to the pubis and Cooper's ligament (in the subsequent
      27 patients), no recurrences have been documented. CONCLUSIONS: Although
      technically demanding and time-consuming, the LRSPH is safe and technically
      feasible. Moreover, it results in a low recurrence rate and is applicable to
      large or multiply recurrent hernias. Transabdominal suture fixation to the bony
      and ligamentous structures produces a more durable hernia repair.

PMID- 15580441
TI  - A prospective randomized study comparing open vs laparoscopy-assisted distal
      gastrectomy in early gastric cancer: early results.
AB  - BACKGROUND: We conducted a prospective randomized trial to compare laparoscopy
      assisted distal gastrectomy (LADG) including lymphadenectomy with open distal
      gastrectomy for the management of early gastric cancer (EGC). METHODS: Forty
      seven patients who had been diagnosed endoscopically with EGC were included in a
      study that ran from November 2001 to August 2003. With the aid of random number
      table, 23 patients were assigned to the open group (group O) and 24 patients were
      assigned to the LADG group (group L). RESULTS: Estimated blood loss and
      transfusion amounts were similar in the two groups. The mean postoperative
      hospital stay and the duration of analgesic administration were shorter for group
      L but not significantly so. The mean number of harvested lymph nodes was 38.1 in
      the O group and 31.8 in the L group (p = 0.098). Postoperative pulmonary
      complications occurred more frequently in the O group (p = 0.043). At a median
      follow-up of 14 months, there has been no recurrence of disease in either group.
      CONCLUSION: In terms of resulting in fewer pulmonary complications while
      maintaining the curability of EGC, LADG has a clear advantage over its open
      counterpart.

PMID- 15580442
TI  - Prevention of lens condensation in laparoscopic surgery by lens heating with a
      thermos flask.
AB  - Condensation on the scope lens as a result of differences between room and
      intraabdominal temperatures is a disturbing problem for laparoscopic surgeons.
      Despite the use of anti-lens condensation solutions, this cannot be entirely
      avoided. The authors report a simple, cheap, and effective method for preventing
      lens condensation by lens heating using a sterilized thermos flask filled with
      hot water.

PMID- 15580443
TI  - Multimedia presentations in the age of the Health Insurance and Accountability
      Act.
AB  - The privacy rule of the Health Insurance Portability and Accountability Act
      (HIPAA) has made all physicians think more about their patients' privacy. In
      addition to safeguarding health information in routine office practice, doctors
      now are starting to consider the effects of the regulations on other professional
      activities including professional clinical multimedia presentations. This article
      explains specifically where and how multimedia (e.g., images, video) patient
      information may be used and shared. Although HIPAA itself is a lengthy and
      detailed document, a few simple rules can be extracted, which when followed,
      ensure that neither presentations nor patient privacy need to be sacrificed.

PMID- 15580444
TI  - Comparison of economic and environmental impacts between disposable and reusable
      instruments used for laparoscopic cholecystectomy.
AB  - BACKGROUND: The economic and environmental effects were compared between
      disposable and reusable instruments used for laparoscopic cholecystectomy.
      Special consideration was given to the processing of reusable instruments in the
      Miele G 7736 CD MCU washer disinfector and the resultant cost of sterilization.
      METHODS: The instruments frequently used in their disposable form were identified
      with the help of surgeons. Thus, of all the instruments used for laparoscopic
      cholecystectomy, the disposable and reusable versions of trocars, scissors, and
      Veress cannula were compared. RESULTS: For the case examined in this study, the
      performance of laparoscopic cholecystectomy with disposable instruments was 19
      times more expensive that for reusable instruments. The higher cost of using
      disposable instruments is primarily attributable to the purchase price of the
      instruments. The processing of reusable instruments has little significance in
      terms of cost, whereas the cost for disposing of disposable instruments is the
      least significant factor. The number of laparoscopic cholecystectomies performed
      per year does not substantially influence cost. In the authors' opinion,
      assessment of the environmental consequences shows that reusable instruments are
      environmentally advantageous. CONCLUSIONS: Considering the upward pressure of
      costs in hospitals, disposable instruments should be used for laparoscopic
      cholecystectomy only if they offer clear advantages over reusable instruments.

PMID- 15580445
TI  - The effect of timing of pneumoperitoneum on the inflammatory response.
AB  - BACKGROUND: We examined the effects of an identical period of pneumoperitoneum
      applied at three different time points after lipopolysaccharide (LPS) challenge.
      Two different insufflation gases were also compared. METHODS: Male rats (n = 70)
      were injected intravenously with 1 mg/kg of LPS (time 0). The time relationship
      between a 1.5-h period of insufflation and initial LPS stimulation was the
      experimental variable. All rats were killed 6 h after injection. CO2 and helium
      insufflation were investigated. Ten control rats received LPS only. Serum
      interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assay
      (ELISA). Hepatic expression of alpha2-macroglobulin, beta-fibrinogen, and
      metallothionein were measured by Northern blot analysis. Statistical analysis was
      performed using one-way analysis of variance (ANOVA). RESULTS: Expression of
      alpha2-macroglobulin mRNA was lower in CO2 groups compared to the control group
      (p < 0.05 at time 120 and 270). beta-Fibrinogen message was diminished in CO2 0
      and 120 groups compared to control. Serum levels of IL-6 and expression of
      metallothionein mRNA did not show significant differences between groups.
      CONCLUSIONS: These findings suggest that CO2 pneumoperitoneum downregulates the
      inflammatory response to LPS challenge. Start time of CO2 insufflation does not
      appear to alter hepatic expression of acute phase genes. The mechanism of alpha2
      macroglobulin downregulation does not appear to be due to IL-6.

PMID- 15580446
TI  - Laparoscopic hepaticojejunostomy for biliary strictures: the experience of 10
      patients.
AB  - Hepaticojejunostomy is performed to reestablish bilioenteric continuity. During a
      5-year period between July 1998 and July 2003, the authors attempted
      hepaticojejunostomy by a total laparoscopic approach in 10 patients with benign
      stricture disorders of the extrahepatic biliary tree. Six of these patients had
      type 1 (extrahepatic, fusiform) choledochal cyst and presented with pain, fever,
      and jaundice. Four of the patients had iatrogenic biliary strictures after
      cholecystectomy (2 patients after laparoscopic cholecystectomy and 2 patients
      after open cholecystectomy). These patients had a variable presentation 1 to 3
      weeks after the primary procedure, with peritonitis and/or cholangitis or only
      progressive jaundice. For nine of the patients (90%), the procedure was completed
      entirely laparoscopically. The mean operative time was 326.6 min for the patients
      with choledochal cysts and 268 min for the patients with iatrogenic strictures.
      One patient with stricture after open cholecystectomy underwent conversion to an
      open repair because of severe anatomic distortion and fibrosis. Four patients
      drained bile postoperatively for 5 to 7 days. One patient with iatrogenic biliary
      stricture after open cholecystectomy required open revision of the anastomosis 18
      months after laparoscopic hepaticojejunostomy because of recurrent cholangitis.
      The remaining eight patients (80%) were doing well a mean follow-up period of 3.1
      years (range, 3 months to 5 years). Total laparoscopic hepaticojejunostomy is
      feasible for a select group of patients, but requires advanced laparoscopic
      skills, including intracorporeal suturing. It must be attempted only in centers
      well versed in advanced laparoscopic surgery.

PMID- 15580447
TI  - Band slippage after laparoscopic adjustable gastric banding: etiology and
      treatment.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is a safe and effective
      procedure for the management of morbid obesity. However, band slippage is a
      common complication with variable presentation that can be rectified by a second
      laparoscopic procedure. METHODS: We studied case series of 125 consecutive
      patients who suffered from band slippage between November 1996 and May 2001 from
      a group of 1,480 laparoscopic adjustable gastric banding procedures performed
      during this time. The decision of whether to remove or replace/reposition the
      band was made prior to the operation, although the specific method used when
      replacement or repositioning was deemed suitable was determined by the operative
      findings. A laparoscopic approach was used in all but three patients. RESULTS: A
      total of 125 patients (8.4%) suffered band slippage (posterior slippage, 82.4%;
      anterior slippage, 17.6%). In 70 patients (56%), the band was removed, whereas in
      55 patients (44%) it was repositioned or replaced immediately. Of these 55
      patients, six underwent later removal, five due to recurrent slippage and one due
      to erosion. Fourteen patients suffered complications, including gastric
      perforation (n = 8), intraoperative bleeding (n = 1), postoperative fever (n =
      3), aspiration pneumonia (n = 1), upper gastrointestinal bleeding (n = 1), and
      pulmonary embolism (n = 1). CONCLUSION: Band slippage is not a rare complication
      after laparoscopic adjustable gastric banding. The decision to remove or replace
      the band or convert to another bariatric procedure should be made preoperatively,
      taking both patient preference and etiology into consideration. Short-term
      results indicate that band salvage is successful when the patient population is
      chosen correctly.

PMID- 15580448
TI  - Mini-laparoscopic appendectomy using a needle loop retractor offers optimal
      cosmetic results.
AB  - BACKGROUND: Do conventional laparoscopic appendectomy (LA) techniques provide
      truly satisfying results for patients and surgeons? We have devised a more
      advanced technique that improves cosmesis. METHODS: A 2-mm scope is inserted at
      the umbilicus, and a 12-mm working trocar is inserted through a suprapubic
      incision placed below the line of pubic hair. A needle loop retractor (NLR) is
      inserted to hold the appendix in the lower right abdomen. In this NLR, a
      stainless steel wire is placed within a needle having a diameter of 2 mm. From
      the suprapubic trocar, a bipolar coagulator is inserted to transect the
      appendiceal mesentery. A series of 30 patients underwent this procedure. RESULTS:
      There were no conversions to laparotomy and no intra- or postoperative
      complications. CONCLUSIONS: Laparoscopic appendectomy using a 2-mm scope,
      suprapubic trocar, and an NLR yields optimal cosmetic results. For surgeons, the
      NLR allows the appendix to be held more firmly than then a 5- or 2-mm grasping
      forceps is used.

PMID- 15580449
TI  - [Barrett's esophagus].
AB  - INTRODUCTION: It is widely accepted that long segments of Barrett's esophagus are
      caused by end-stage gastroesophageal reflux disease (GERD), but little is known
      about the correlation of severity of GERD and extent of metaplasia. METHODS:
      Twenty normal volunteers and 142 patients with different extent of intestinal
      metaplasia (39 with intestinal metaplasia limited to the esophagogastric
      junction, 48 with short segments of Barrett's esophagus, and 55 with long
      segments) underwent manometry and combined pH-bilirubin monitoring. RESULTS: The
      extent of intestinal metaplasia correlated to the exposition of gastric and
      duodenal juice in the esophagus and inversely with a competent lower esophageal
      sphincter. CONCLUSIONS: The extent of intestinal metaplasia is related to the
      severity of GERD.

PMID- 15580450
TI  - [Cryosurgical treatment of actinic keratoses and evidence-based review].
AB  - BACKGROUND: Actinic keratoses are focal epithelial carcinomas in situ, which are
      considered precursors of squamous cell carcinoma and must therefore be treated.
      In the USA, cryosurgery is the most frequent surgical procedure for the treatment
      of actinic keratoses and considered the treatment of choice. METHODS: Our own
      results of cryosurgical treatment of actinic keratoses were evaluated. Original
      publications and reviews on the treatment of actinic keratoses with cryosurgery
      were retrieved from MEDLINE and classified according to their evidence level.
      RESULTS: Two months after the procedure, 97.0% of the lesions (n=99) were
      considered sufficiently treated. Local pain during and shortly after treatment
      (15%) and pigmentary changes (5%) were the most frequent side effects.
      Recurrences were detected in 2.1% of the lesions during the 1st year and in 11,5%
      after 3 years. In 2 further monotherapy studies recurrences occurred in 1,2-9% of
      the lesions after one year in 30% after 3 years. Literature data suggest that
      photodynamic therapy is equally or even more effective than cryosurgery after a 3
      month follow-up. The cryosurgical results were strongly dependent on the
      attending physician. CONCLUSIONS: Cryosurgery is beneficial in the treatment of
      actinic keratoses. This method is equivalent to photodynamic therapy.

PMID- 15580451
TI  - [Venous leg ulcers: no improvement of wound healing with 685-nm low level laser
      therapy. Randomised, placebo-controlled, double-blind study].
AB  - INTRODUCTION: Venous leg ulcers (ulcera crurum venosa) are frequently seen in
      elderly patients. It has been suggested that low level laser irradiation has a
      biostimulative and wound healing effect; however, this has not yet been
      clinically verified by controlled studies. STUDY DESIGN: The difference in size
      reduction of leg ulcers with and without low level laser or placebo laser
      treatment was measured in 44 patients randomised into two treatment groups (685
      nm low level laser and placebo laser) or a control group which served to quantify
      the effect of laser application. All patients received standardized wound care.
      OBJECTIVE: The aim of the study was to compare the effectiveness of low level
      laser irradiation with that of a placebo "light source". The size of the ulcers
      was planimetrically measured at baseline (day 1), at the end of therapy (day 28)
      and 2 months later (day 90). The difference in wound size was evaluated. RESULTS:
      There were no statistically significant differences in reduction of wound size
      between the three groups, thus suggesting that low level laser light does not
      have any stimulatory effect on wound healing in ulcera crurum venosa.

PMID- 15580452
TI  - [Alefacept. Successful long-term therapy of a severe psoriasis].
AB  - Alefacept, a recombinant protein produced by fusion of human LFA(3 )and IgG(1),
      was the first biologic specially designed and approved for the treatment of
      psoriasis. Results of clinical trials reveal both an efficacy comparable to
      established systemic therapies and a high drug safety. A 62-year old male patient
      with psoriasis and incomplete response to several standard therapies was treated
      with alefacept (baseline PASI 23.1). After three courses of 15 mg alefacept i.m.
      weekly for 12 weeks, each followed by a 12 week post-dosing observation period,
      the PASI regressed to 2.0. Adverse drug reactions were not observed.

PMID- 15580453
TI  - [Successful treatment of subcorneal pustular type of IgA pemphigus].
AB  - IgA pemphigus is a rare autoimmune intraepidermal blistering disease
      characterized by in vivo bound, and circulating IgA autoantibodies that target
      cell surface components (cadherins) of epidermal keratinocytes. The average age
      of onset is approximately 50 years. Histological hallmarks of IgA pemphigus are
      epidermal acantholysis, subcorneal or intraepidermal pustulosis, and neutrophilic
      infiltration. The main clinical characteristics are erythematous skin lesions
      with vesiculopustules, erosions, crusts and desquamation, favoring the trunk,
      groins, auxiliaries, and proximal extremities. The drug of choice for treating
      IgA pemphigus is diaminodiphenylsulfone. In this case study, we describe a
      patient who suffered from IgA pemphigus and responded well to
      diaminodiphenylsulfone.

PMID- 15580454
TI  - [Acral pseudolymphomatous angiokeratoma of children (APACHE)].
AB  - Acral pseudolymphomatous angiokeratoma of children (APACHE) is a pseudolymphoma
      of posttraumatic origin which was first described in 1988. We report on a female
      patient with APACHE following a traumatic abrasion on her foot. Reddish papules
      developed that histologically were characterized by a wedge-shaped inflammatory
      infiltrate rich in capillaries. Conservative treatment was not successful.

PMID- 15580455
TI  - [Endolaryngeal swelling with dyspnoea].

PMID- 15580456
TI  - [Painful swelling of the soft tissue of the neck].

PMID- 15580457
TI  - [Determination of subjective impairment in dysphonia. A methodological
      comparison].
AB  - OBJECTIVE: The purpose of this study was to estimate the correlation between the
      voice handicap index (VHI) and the voice related quality of life (VRQOL)
      questionnaire with respect to gender and diagnosis (functional vs organic
      dysphonia). MATERIALS AND METHODS: A total of 52 German speaking patients aged
      48.8+/-22.0 years suffering from dysphonia of different benign etiologies
      (functional dysphonia: 18 women, 9 men; organic dysphonia: 13 women, 12 men)
      completed German versions of both the VHI and the VRQOL questionnaire without
      prior information on their individual diagnosis. Another 52 individuals without
      voice complaints served as age and sex matched controls. Complete data sets of
      all participants were analyzed using the Microsoft Excel and MATLAB software
      packages. RESULTS: The results of both questionnaires correlate at a significant
      level, both for total score (r=-0.9) and the subscores (r=-0.74-r=-0.84) with
      only slight differences when comparing women and men and patients with functional
      and organic voice disorders. CONCLUSIONS: Both questionnaires provide very
      similar results. Thus, for clinical purposes, it seems justified to restrict
      oneself to using only one of the questionnaires. Whenever basic information on
      the patients' self perception of a voice disorder is required, the VRQOL
      questionnaire with only ten items may be easier to handle than the VHI
      questionnaire with 30 items.

PMID- 15580458
TI  - [Pitfalls in ossicular chain reconstruction].
AB  - Today, the reconstruction of the ossicular chain is standard in middle ear
      surgery. It is performed as a one step procedure in cases of non-inflamed middle
      ears, as well as in cases of chronic ear diseases. In contrast to the past, a
      large tympanic cavity is today regularly reconstructed, which contributes to a
      normally ventilated middle ear. Reconstruction of the ossicular chain is
      necessary to keep the tympanic membrane in its normal position.However, many
      modern prostheses are available with different designs and material properties.
      This article aims to give an overview of the acusto-mechanical and surgical
      aspects of ossicular chain reconstruction. After a description of normal middle
      ear vibration, the biomechanical background of the reconstructed middle ear
      (incus reconstruction, stapes reconstruction) is discussed.

PMID- 15580459
TI  - [Metabolic syndrome: diagnosis and dietary intervention].
AB  - The metabolic syndrome is diagnosed according to criteria set by either WHO
      (obesity, high blood pressure, dyslipidemia, insulin resistance) or more recently
      by ATP III (National Cholesterol Education Program's Adult Treatment Panel III
      report). The latter emphasizes abdominal obesity, atherogenic dyslipidemia, high
      blood pressure and increased fasting glucose. Without presuming a nosologic
      entity, the metabolic syndrome is emerging as by far the most important precursor
      of an epidemic of cardiovascular disease, not only in Western countries. This
      epidemic calls for action at a time when our understanding of dietary
      intervention for maintaining weight loss remains primitive and cannot withstand
      critical scrutiny (because of a lack of long term randomised, prospective
      studies). Dietary therapy in metabolic syndrome therefore has to be aimed where
      success is most likely, i.e. at a reduction in energy intake and increase in
      output by physical activity, a prudent balance of carbohydrates, proteins and
      fats, taking into account secondary changes in lipid profiles and the glycemic
      load of nutrients. All nutritional advice must be incorporated in long term
      programs with continuous guidance, preferably in group therapy targeting all
      individual risk factors.

PMID- 15580460
TI  - [Infection-related emergencies in oncology].
AB  - Infections in immunosuppressed patients have always to be regarded as
      emergencies, as they have a high rate of complications and mortality. The most
      important risk factor is severity and duration of granulocytopenia. Risk scores
      help to identify patients who, despite their immune deficiency have a low risk of
      complications. Diagnostic measures to identify the causative microorganism and
      the source of infection is necessary. However, diagnostic investigation must not
      delay the immediate onset of antimicrobial treatment. Patients often have to be
      treated empirically as the identification of the causative microorganism or the
      source of infection are often unknown at the beginning of clinical symptoms.
      Empirical treatment has to be broad to cover possible microorganisms. Especially
      meningitis, abdominal infections, sepsis and pneumonia can be regarded as
      infectiological emergencies. Patients with these infections have to be treated
      with intensive antimicrobial treatment, taking into account the possible
      causative agents.

PMID- 15580461
TI  - [Acute renal failure].
AB  - The acute renal failure is characterized by a rapid deterioration of the renal
      function. In addition to the usual prerenal, intrinsic and postrenal causes of an
      acute renal failure distinct causes have to be considered for oncological
      patients. Factors imminent to the malignant disease, e. g. paraneoplastic
      syndromes or retroperitoneal bulks can account for an acute renal failure.
      Paraproteins as produced by a multiple myeloma are other possible causes for
      renal dysfunction. For some anticancer drugs nephrotoxicity is a potential side
      effect, in particular for cisplatin, methotrexate, ifosfamide and melphalan. A
      hemolytic uremic syndrome may be induced by mitomycin and gemcitabine. Extensive
      surgery can be associated with rhabdomyolysis and myoglobinuria and results in
      renal impairment. Treatment of a chemosensitive neoplasia with a highly effective
      regimen may result in a tumor lysis syndrome with hyperuricemia, hyperkalemia,
      hyperphosphatemia and hypocalcemia.

PMID- 15580462
TI  - [Acute central nervous symptoms in oncologic patients].
AB  - Oncologic patients may suffer from acute central nervous system disorders either
      related to the disease itself or to its therapy. These disorders may present as a
      disturbance of consciousness, as mental changes, as focal neurological signs, as
      epileptic seizures or as a combination of these. Symptoms may be caused by
      cerebral metastases, hemorrhage, ischemia or infectious complication, by
      metabolic changes or by treatment sequealae. This article will focus on clinical
      presentation, diagnostic workup and possible therapy or prophylaxis of these
      complications.

PMID- 15580463
TI  - [Vertebrobasilar ischemia as a complication of temporal arteritis. Results of a
      prospective, clinical, ultrasonographic study].
AB  - BACKGROUND: Cerebral symptoms in temporal arteritis (TA) may occur if large
      arteries are affected. To avoid progression of the disease, the immediate
      administration of adequate doses of steroids is mandatory. PURPOSE: The
      prevalence and severity of vertebrobasilar ischemia (VBI) and its relation to
      structural abnormalities of the vertebral arteries were studied. METHODS:
      Clinical and ultrasound data were analyzed in a hospital-based group of 91
      patients who received the diagnosis of TA following standard criteria. RESULTS:
      In contrast to the occurrence of neuro-ophthalmological complications (27.5%),
      the rate of VBI was low (4.4%). TIA occurred in three cases and mild stroke in
      one. Ultrasound demonstrated severe occlusive disease of the extradural parts of
      the vertebrobasilar arteries consisting of hypoechogenic, concentric, mural
      thickening. The same was found in the superficial temporal arteries. CONCLUSIONS:
      In elderly patients presenting with VBI, TA affecting the vertebral arteries
      should be considered. In experienced hands, ultrasonography allows the atraumatic
      preliminary diagnosis of TA.

PMID- 15580464
TI  - [Gamma-hydroxybutyrate--a neurotransmitter, medicine, and drug].
AB  - Gamma-hydroxybutyrate (GHB) is a short fatty acid and physiologic
      neurotransmitter. Initially, it was synthesized as a GABA agonist and used as a
      narcotic agent, because it rapidly induces sleep without major cardiovascular or
      respiratory side effects. Recently, a specific GHB receptor was identified, but
      while the clinical use of GHB as an anaesthetic was reduced due to putative pro
      convulsive effects, it now is used to treat alcohol withdrawal and sleep
      disorders. Furthermore, GHB was postulated to be a regulator of energy
      metabolism, and tissue-protective effects were demonstrated in different animal
      models. Besides its clinical use, GHB (also called "liquid ecstasy") is
      increasingly consumed in the disco scene because of its mild sedative and
      euphoric effects. Intoxication from GHB is common with GHB users. For this reason
      and because GHB is not easy to detect, it is important to be aware of the
      symptoms of GHB intoxication. Moreover, some recent case reports document the
      danger of GHB dependence.

PMID- 15580465
TI  - [Care requirements for severe mental disorders. Scientific evidence for
      integration of clinical psychiatry and community psychiatry].
AB  - In Germany it is not clear which forms of community mental health care should be
      encouraged to meet the needs particularly of the severely mentally ill. We
      performed a literature review of systematic meta-analyses and controlled trials
      and show that a set of well-evaluated and effective psychiatric care systems is
      available, of which only a few are being implemented in Germany. It becomes
      obvious that in Germany organizational requirements for an integration of
      psychiatric services are not being adequately met, particularly in the case of
      schizophrenia. Team-based assertive community treatment, crisis intervention
      teams, community mental health teams, and modern job rehabilitation programs,
      which have been established primarily in English-speaking countries, could not be
      effectively adapted for German psychiatric care. At the same time many
      psychiatric care models have been poorly evaluated. Given the available
      scientific evidence we comment on future requisites and further developments in
      German psychiatry to meet the growing need of care for people with severe mental
      illnesses.

PMID- 15580466
TI  - [Psychiatry in the journal "Der Nervenarzt" 1928-2000].
AB  - By analysing the complete edition of the German-language psychiatric journal "Der
      Nervenarzt" from 1928 to 2000 we examined basic trends in the historical and
      scientific orientation of psychiatry in this journal. All published articles
      (n=3270) were classified under formal aspects and were assigned to one of 30
      categories by content. Inter-rater reliability was determined in 3 years from
      different eras (1957, 1977, 1997). With kappa values between 0.65 and 0.81 the
      inter-rater reliability was moderate to good. The mean number of authors and the
      mean number of references in the articles has been increasing continuously,
      particularly within the last decade. The mean number of words per article has
      been relatively constant. In nearly all 5-year periods, most of the articles came
      from Heidelberg, Munich and Berlin. In addition to original articles, review
      articles were introduced in 1971 and medical education articles in 1978. Since
      1955 the "Nervenarzt" has been publishing the communications of the German
      Psychiatric and Neurological Society. Original articles with data reports and
      articles using statistics have been increasing continuously since the 1960s,
      reflecting an increasing evidence-based orientation of psychiatry. The currently
      accepted scientific standard was introduced in the early 1990s. The last decade,
      the "decade of the brain", not only yielded a high proportion of articles on
      biological issues but also indicated an increasing interest in institutions of
      psychiatric care and psychotherapy. On the other hand, links to related
      disciplines such as philosophy, sociology and psychology seem to have got lost.
      The percentage of articles from abroad has been decreasing within the last 2
      decades. In comparison, the American Journal of Psychiatry, the Archives of
      General Psychiatry and the British Journal of Psychiatry have been publishing a
      higher percentage of original articles, particularly randomised controlled
      trials.

PMID- 15580467
TI  - [Acute disseminated encephalomyelitis. Pathogenesis, diagnosis, treatment, and
      prognosis].
AB  - Acute disseminated encephalomyelitis (ADEM) is typically a monophasic,
      demyelinating disease of the CNS that predominantly affects children. Typically,
      its clinical symptoms follow an infection or vaccination. In this regard,
      numerous viral and bacterial pathogens as well as several vaccinations have been
      associated with ADEM. Studies from animal models suggest that primary and
      secondary autoimmune responses may contribute to CNS inflammation and
      demyelination in ADEM. The diagnosis of ADEM is strongly suggested by a close
      temporal relationship between a viral infection or immunization and the onset of
      neurologic symptoms, and it is supported by extensive, multifocal, subcortical
      white-matter disease on brain magnetic resonance imaging. While mild lymphocytic
      pleocytosis and elevated proteins are detectable in the CSF in ADEM, oligoclonal
      bands are not always present. Treatment of this disorder consists of anti
      inflammatory and immunosuppressive therapies, and the prognosis is generally
      considered favorable.

PMID- 15580468
TI  - [The role of the immune system in hereditary demyelinating neuropathies].
AB  - Hereditary neuropathies, e.g., Charcot-Marie-Tooth (CMT) disease, are inherited
      diseases of the peripheral nervous system causing chronic progressive motor and
      sensory dysfunction. Most neuropathies are due to mutations in myelin genes such
      as PMP22, P0, and the gap junction protein Cx32. Myelin mutant mice are regarded
      as suitable animal models for several forms of hereditary neuropathies and are
      important neurobiological tools for the evaluation of pathogenetic and
      therapeutic concepts in hereditary neuropathies. Using these animal models we
      could recently show that the immune system is involved in the pathogenesis of
      hereditary neuropathies. Due to the phenotypic similarities we also consider the
      immune system important for human inherited neuropathies, in particular since
      several case reports demonstrate a beneficial effect of immune therapies in
      patients with hereditary neuropathies. In this review we compare findings from
      animal models and human disease to elucidate the role of the immune system in
      hereditary neuropathies.

PMID- 15580469
TI  - [Neurosyphilis and neuroborreliosis. Retrospective evaluation of 22 cases].
AB  - We present laboratory data from 22 patients suspected of having neurosyphilis. In
      two cases the suspicion could not be confirmed, and in 20 cases neurosyphilis was
      detected. The sera from 17 patients were also assayed for Borrelia-specific
      antibodies. Suspicious immunoglobulin G antibody indices were detected in nine
      cases and a suspicious immunoglobulin M antibody index in one. In six of these,
      stored CSF/serum pairs were available to specify the antibodies by
      immunoblotting. This allowed for the identification of one patient apparently
      infected by both Borrelia spp. and Treponema pallidum. In all cases of newly
      suspected neurosyphilis, we recommend considering neuroborreliosis at the same
      time.

PMID- 15580471
TI  - [Dysmorphia and psychomotor retardation].

PMID- 15580470
TI  - [Diet and multiple sclerosis].
AB  - Beneficial effects from any particular diet have not been proven in multiple
      sclerosis (MS). Therefore, the general guidelines on nutrition should be
      followed. Obesity and various forms of malnutrition worsening the MS symptoms are
      frequently observed. There is some evidence from epidemiological studies that a
      high consumption of saturated animal fat is associated with an increased
      incidence of MS. The findings from such studies indicate that supplementation
      with unsaturated fatty acids, in particular omega-3 fatty acids, could positively
      influence the course of MS. However, controlled studies did not show clear
      beneficial effects from polyunsaturated fatty acids. The intake of vitamin D is
      associated with a lower incidence of MS. In contrast, the effects of therapy with
      vitamin D on the course of MS have not been ascertained. Patients with MS carry
      an enormous risk of osteoporosis, and therefore the indication for a preventive
      therapy with vitamin D and calcium should be established in every postmenopausal
      woman or after repeated steroid treatments.

PMID- 15580472
TI  - [Electrostimulation in therapy of postoperative urinary incontinence. Therapeutic
      value for quality of life].
AB  - Worldwide use of electrical stimulation for therapy of postoperative incontinence
      is based on a few prospective randomized controlled studies. We present a three
      arm prospective randomized study evaluating physiotherapeutic pelvic floor
      training alone and in combination with transanal or perineal electrical
      stimulation. The study compared specific continence training (CT) and a
      combination of CT with transanal or perineal electrostimulation. The groups
      included 60 patients each and were analyzed with regard to self-assessment,
      objective characteristics of incontinence, standard quality of life questionnaire
      (QLQ-C 30), and recorded data of the stimulation device. The patients
      participated in a specific inpatient rehabilitation program and were assessed at
      the time of admittance, upon discharge, and again after 3 months. Significant
      improvement could be achieved in every group concerning urinary incontinence and
      quality of life. Additional use of electrical stimulation was significantly
      superior to physiotherapeutic training alone. However, these results could only
      be detected in a highly compliant subgroup. Analysis of device data indicated a
      high score of errors and lack of patient compliance. Perineal electrical
      stimulation was better accepted than transanal and showed less side effects and
      better outcome in the characteristics of incontinence. Improvement in the quality
      of life was mostly achieved during the weeks of inpatient rehabilitation.
      Electrical stimulation could not improve quality of life items. Electrical
      stimulation is an efficient instrument for treatment of postoperative high-grade
      incontinence, however, only with sufficient patient compliance.

PMID- 15580473
TI  - Genetic diversity and geographic pattern in early South American cotton
      domestication.
AB  - Amplified fragment length polymorphism fingerprinting was applied to survey the
      genetic diversity of primitive South American Gossypium barbadense cotton for
      establishing a possible link to its pre-Columbian expansion. New germplasm was
      collected along coastal Peru and over an Andean transect in areas where most of
      the archaeological evidence relating to cotton domestication has been recorded.
      Gene bank material of three diploid (G. raimondii, G. arboreum, and G. herbaceum)
      and four allotetraploid cotton species (G. hirsutum, G. mustelinum, G. tomentosum
      and additional G. barbadense) was added for inter- and intra-specific comparison.
      Eight primer combinations yielded 340 polymorphic bands among the 131 accessions.
      The obtained neighbor joining and unweighted pair-group method with arithmetic
      means are in full agreement with the known cytogenetics of the tetraploid cottons
      and their diploid genome donors. The four tetraploid species are clearly distinct
      based on taxonomic classification. The genetic diversity within G. barbadense
      reveals geographic patterns. The locally maintained cottons from coastal Peru
      display a distinct genetic diversity that mirrors their primitive agro
      morphological traits. Accessions from the northernmost coast of Peru and from
      southwestern (SW) Ecuador cluster basal to the east-of-Andes accessions. The
      remaining accessions from Bolivia, Brazil, Columbia, Venezuela, and the Caribbean
      and Pacific islands cluster with the east-of-Andes accessions. Northwestern
      Peru/SW Ecuador (the area flanking the Guayaquil gulf) appears to be the center
      of the primitive domesticated G. barbadense cotton from where it spread over the
      Andes and expanded into its pre-Columbian range.

PMID- 15580474
TI  - Steroid-induced myopathy in patients intubated due to exacerbation of chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To determine incidence, risk factors and impact on various outcome
      parameters of the development of acute quadriplegic myopathy in a selected
      population of critically ill patients. SETTING: A prospective cohort study
      carried out in the intensive care unit of a tertiary-level university hospital.
      PATIENTS: All patients admitted due to acute exacerbation of chronic obstructive
      pulmonary disease who required intubation and mechanical ventilation, and
      received high doses of intravenous corticosteroids. INTERVENTIONS: A
      neurophysiological study was performed in all cases at the onset of weaning.
      Muscular biopsy was taken when the neurophysiological study revealed a myopathic
      pattern. MEASUREMENTS AND RESULTS: Twenty-six patients were enrolled in the
      study. Nine patients (34.6%) developed myopathy. Only seven patients were treated
      with muscle relaxants. Histology confirmed the diagnosis in the three patients
      who underwent muscle biopsy. APACHE II score at admission, the rate of sepsis and
      the total doses of corticosteroids were significantly higher in patients with
      myopathy compared with those patients that did not develop it. Myopathy is
      associated with an increase in the duration of mechanical ventilation [15.4 (9.2)
      versus 5.7 (3.9) days; p<0.006], the length of ICU stay [23.6 (10.7) versus 11.4
      (7.05) days; p<0.003] and hospital stay [33.3 (19.2) versus 21.2 (16.1) days;
      p<0.034)]. Myopathy was not associated with increased mortality. CONCLUSIONS: In
      the population under study, severity of illness at admission, the development of
      sepsis and the total dose of corticosteroids are factors associated with the
      occurrence of myopathy after the administration of corticosteroids. Myopathy was
      associated with prolonged mechanical ventilation and in-hospital stay.

PMID- 15580475
TI  - Endotracheal tube intraluminal diameter narrowing after mechanical ventilation:
      use of acoustic reflectometry.
AB  - OBJECTIVE: To quantify the incidence and degree of endotracheal tube intraluminal
      obstruction after mechanical ventilation and its relation to time of intubation.
      DESIGN: Prospective observational study. SETTING: A 14-bed medical-surgical
      intensive care unit at a university-affiliated teaching hospital. PATIENTS:
      Ninety-four endotracheal tubes used in 80 patients requiring mechanical
      ventilation for more than 12 h. INTERVENTIONS AND RESULTS: Acoustic reflectometry
      was performed in every endotracheal tube after patient extubation to measure its
      volume reduction. The intraluminal volumes of used endotracheal tubes in
      mechanically ventilated patients were significantly lower than those of unused
      tubes of the same size (5.52+/-0.92 ml(3) versus 6.54+/-0.79 ml(3), p<0.05). The
      mean difference in endotracheal tube segment volumes was 15.2% (range 0-66%).
      Volume reduction was above 10% in 60.8% of the tubes. In 22% of endotracheal
      tubes the remaining inner diameter was less than 7 mm. Reduction below this
      figure was less frequent (9.3%) in tubes 8 mm or more (p<0.05). The percentage of
      endotracheal tube volume reduction was not associated with the duration of
      intubation (r=-0.09, p= n.s.) Peak pressure measured before extubation did not
      predict obstruction (r=0.11, p= n.s.). CONCLUSIONS: Inadvertent endotracheal tube
      obstruction was common in patients requiring mechanical ventilation and may be
      significant as early as at 24 h. Moderate obstruction in endotracheal tube lumens
      should be suspected in cases of difficulties in weaning, even in patients who
      were ventilated for less than 1 day.

PMID- 15580479
TI  - Risk of fracture among women who lose bone density during treatment with
      alendronate. The Fracture Intervention Trial.
AB  - It is commonly believed that the response to treatment in patients on alendronate
      is proportional to the increase in bone mineral density (BMD), and that those who
      lose BMD during treatment might not respond to treatment. In the Fracture
      Intervention Trial 6,459 women were randomly assigned to treatment with
      alendronate or placebo; BMD was measured annually, and new spine fractures were
      assessed by lateral spine films, taken at baseline and end of follow-up. Among
      subjects who took at least 70% of the study drug (5,220 women), we compared
      reductions in risk of spine fractures at end of follow-up (3 or 4 years) within
      various levels of change in total hip and spine BMD after 1 and 2 years of
      treatment, after adjustment for differences in characteristics between the
      treatment and control groups. Women "losing" BMD at the lumbar spine (0% to 4%)
      while on alendronate had a reduction of 60% in vertebral fracture risk [OR = 0.40
      (0.16, 0.99)] compared to their counterparts in the placebo group. The few women
      that lost more than 4% did not have a significant benefit [OR = 0.15 (0.02,
      1.29)]. Those who "gained" BMD (0% to 4%) during treatment had a reduction in
      risk of 51% [OR = 0.49 (0.30, 0.78)]. Similarly, women who "lost" total hip BMD
      (0% to 4%) during the first year on alendronate had a 53% decreased risk of
      vertebral fracture compared to their controls taking placebo [OR = 0.47 (0.27,
      0.81)], whereas those "gaining" BMD (0% to 4%) had a comparable risk reduction
      [OR = 0.49 (0.34, 0.71)]. This was not observed for the few women who lost more
      than 4% [OR = 0.61 (0.11, 3.45)]. Patients who lost BMD at both the hip and spine
      were not protected by alendronate. Among patients who adhere to treatment with
      alendronate, even those who lose BMD benefit from a substantial reduction in risk
      of vertebral fracture. So, the reduction in bone turnover induced by alendronate
      might be more important than BMD changes. The few women who lose the most BMD
      (more than 4% per year) might not benefit from the treatment.

PMID- 15580480
TI  - A population-based study of osteoporosis testing and treatment following
      introduction of a new bone densitometry service.
AB  - Bone density measurement plays a key role in the initial diagnostic assessment of
      osteoporosis and in targeting pharmacologic therapies. The impact of access to
      dual-energy X-ray absorptiometry (DXA) on physician prescribing habits is
      unclear, however. We were able to directly evaluate the change in physician
      osteoporosis testing and prescribing following introduction of a DXA testing
      service in a geographic region that had previously had very limited access. This
      evaluation was conducted in the province of Manitoba, Canada, which has a
      provincially based bone density testing program and maintains a population-based
      bone density database that can be linked with administrative health data sources
      including drug prescriptions. The province of Manitoba was geographically
      partitioned into the urban and rural health regions serviced by the new program
      (urban(new )and rural(new)) and the remaining urban and rural health regions
      which had relatively unchanged DXA access during this period (urban(control) and
      rural(control)). Regression models of DXA testing rates and osteoporosis
      prescription rates were created for all older women in these regions. There was a
      statistically significant increase in bone density testing and BMD-guided
      osteoporosis treatment in the urban(new) and rural(new) regions following
      introduction of the DXA testing service, relative to the control regions.
      Although the overall rate of empiric postfracture and preventive osteoporosis
      treatment did not show a specific region effect, when analysis was limited to
      nonhormonal agents there was a significant reduction in preventive and empiric
      postfracture treatment in some subgroups of women. These results suggest that the
      local availability of the bone density testing service led to an increase in
      objective test-guided therapy with some reduction in the use of empiric and
      preventive strategies and had a neutral effect on overall use of these agents.

PMID- 15580483
TI  - Repeated administration of AMPA or a metabotropic glutamate receptor agonist into
      the rat ventral tegmental area augments the subsequent behavioral hyperactivity
      induced by cocaine.
AB  - RATIONALE: Glutamate receptors and their related second messengers in the ventral
      tegmental area (VTA) are known to play critical roles in the initiation of
      behavioral sensitization to cocaine. OBJECTIVES: To evaluate the hypothesis that
      repeated intra-VTA microinjections of the ionotropic glutamate agonist, AMPA, or
      the metabotropic glutamate agonist, t-ACPD, augment the behavioral hyperactivity
      induced by a subsequent challenge injection of cocaine. In addition, the
      dependency of the t-ACPD effect on activation of the calcium/calmodulin-dependent
      kinases (CaM-Ks) was assessed. METHODS: Male Sprague-Dawley rats received four
      once-daily microinjections of saline, AMPA, t-ACPD, or t-ACPD plus the CaM-KII
      inhibitor KN-93 directly into the VTA; locomotor activity was measured for 120
      min after each of the daily treatments. One week after the 4 treatment days, all
      animals received a challenge injection of cocaine (15 mg/kg, IP) and behavioral
      activity was monitored for 120 min. RESULTS: Intra-VTA administration of t-ACPD
      increased behavioral activity only on the first 2 treatment days, an effect that
      was blocked by pre-treatment with KN-93. Administration of AMPA into the VTA, in
      contrast, produced behavioral hyperactivity that sensitized over the 4 treatment
      days. Following the cocaine challenge injection, there was an augmentation of
      cocaine-induced behavioral hyperactivity in the groups pretreated with AMPA or t
      ACPD but not in the animals administered t-ACPD plus KN-93. CONCLUSIONS: These
      results indicate that repeated stimulation of AMPA or metabotropic glutamate
      receptors in the VTA mimics the initiation of behavioral sensitization to
      cocaine. The present findings also suggest that glutamate agonist-induced
      activation of CaM-KII in the VTA plays a critical role in the behavioral and
      neuronal plasticity induced by repeated cocaine injections.

PMID- 15580485
TI  - Motor control goes beyond physics: differential effects of gravity and inertia on
      finger forces during manipulation of hand-held objects.
AB  - According to basic physics, the local effects induced by gravity and acceleration
      are identical and cannot be separated by any physical experiment. In contrast-as
      this study shows-people adjust the grip forces associated with gravitational and
      inertial forces differently. In the experiment, subjects oscillated a vertically
      oriented handle loaded with five different weights (from 3.8 N to 13.8 N) at
      three different frequencies in the vertical plane: 1 Hz, 1.5 Hz and 2.0 Hz. Three
      contributions to the grip force-static, dynamic, and stato-dynamic fractions-were
      quantified. The static fraction reflects grip force related to holding a load
      statically. The stato-dynamic fraction reflects a steady change in the grip force
      when the same load is moved cyclically. The dynamic fraction is due to
      acceleration-related adjustments of the grip force during oscillation cycles. The
      slope of the relation between the grip force and the load force was steeper for
      the static fraction than for the dynamic fraction. The stato-dynamic fraction
      increased with the frequency and load. The slope of the dynamic grip force-load
      force relation decreased with frequency, and as a rule, increased with the load.
      Hence, when adjusting grip force to task requirements, the central controller
      takes into account not only the expected magnitude of the load force but also
      such factors as whether the force is gravitational or inertial and the
      contributions of the object mass and acceleration to the inertial force. As an
      auxiliary finding, a complex finger coordination pattern aimed at preserving the
      rotational equilibrium of the object during shaking movements was reported.

PMID- 15580486
TI  - Levetiracetam in the treatment of vascular chorea: a case report.

PMID- 15580487
TI  - Pharmacoepidemiology and the "impact factor".
AB  - The field of "Pharmacoepidemiology/Drug Utilization" research has been analysed
      by studying published research articles under the medical subject headings (MeSH
      terms) "Pharmacoepidemiology", "Drug Utilization" and "Drug Utilization Review".
      There were 1822 articles published, and stored in Medline, during the 32-month
      period between 1 January 2001 and 31 August 2003; these papers might represent a
      field of research, due to the similarity of MeSH terms used for coding and the
      set of journals in which the articles were published. A total of 457 articles,
      representing 25% of all articles in the field, were published in 14 different
      journals, and 50% of all articles (948) were collected in only 64 different
      journals. The two main journals publishing research in "Pharmacoepidemiology/Drug
      Utilization" are Pharmacoepidemiol Drug Saf and the Eur J Clin Pharmacol. These
      two publications are the official journals of the three main societies in the
      field and are at least partially focused on this subject, with 45.7% of all
      articles in Pharmacoepidemiol Drug Saf and 11.1% of all articles in Eur J Clin
      Pharmacol included under the studied MeSH terms; other journals only occasionally
      publish papers in this line of research. These two journals are the leaders in
      pharmacoepidemiology and drug utilization research, having impact factors (IFs)
      in 2002/2003 above (1.955/1.972 for EJCP) and a bit below (1.092/1.257 for PDS)
      the middle of the ranking of publications, according to the IF, in the
      "Pharmacology and Pharmacy" list of the Science Citation Index (SCI).

PMID- 15580488
TI  - Agranulocytosis associated with dipyrone (metamizol).
AB  - OBJECTIVES: Reported estimates of the risk of agranulocytosis associated with
      metamizol have varied by several orders of magnitude. We assessed this
      association in a large database for the surveillance of blood dyscrasias.
      METHODS: Since 1980, all laboratory units of haematology in a defined area (3.3
      4.1x10(6) inhabitants) contribute to the ascertainment of all cases of
      agranulocytosis meeting strict diagnostic criteria. These cases of patients with
      agranulocytosis and sex-, age-, hospital- and date-matched controls were
      interviewed using a structured questionnaire about previous drug exposures, and
      relative risks were calculated for several categories of exposure to metamizol.
      RESULTS: After a total follow-up of 78.73x10(6) person-years, 273 community cases
      of agranulocytosis had been found--of which 96 were excluded for various reasons
      and 177 were included in the case-control analysis--and were compared with 586
      matched controls. Thirty cases of agranulocytosis (16.9%) and nine controls
      (1.5%) had been exposed to metamizol during the week before the index day. The
      adjusted relative risk was 25.8 [95% confidence interval (CI), 8.4-79.1], and the
      attributable incidence was 0.56 (0.4-0.8) cases per million inhabitants and per
      year. The risk disappeared after more than 10 days since the last dose of
      metamizol, and it increased with duration of use. Those with agranulocytosis
      exposed to metamizol had taken the drug for longer periods than the exposed
      controls. Compared with the cases recently reported from Sweden, the duration of
      use of metamizol by our exposed cases was substantially shorter, and the use of
      concomitant medications potentially causing agranulocytosis was lower.
      DISCUSSION: In our milieu, agranulocytosis attributable to metamizol is rare.
      Geographical disparities in its risk estimate can be partly explained by
      differences in its patterns of use, in terms of dose, duration and concomitant
      medications.

PMID- 15580489
TI  - MR angiography of the intracranial vessels: technical aspects and clinical
      applications.
AB  - Evaluation of the intracranial circulation provides valuable information in the
      diagnosis and prognosis of various intracranial abnormalities and may influence
      patient management. Technical advances in magnetic resonance angiography (MRA)
      have improved the accuracy of this technique in various clinical situations, such
      as aneurysms, arterial and venous steno-occlusive diseases, vascular
      malformations, inflammatory arterial diseases, preoperative assessment of the
      patency of dural sinuses, and congenital vascular abnormalities. In many centers,
      MRA has replaced conventional digital subtraction angiography in screening for
      intracranial vascular disease, because of its non-invasive and non-ionizing
      character. Several MRA techniques have been developed for the imaging of the
      intracranial vascular system, such as time-of-flight MRA (TOF MRA), phase
      contrast MRA (PC MRA), and more recently contrast-enhanced MRA (CE MRA). In the
      evaluation of steno-occlusive disease, the three-dimensional (3D) TOF-MRA
      technique is recommended for arterial evaluation, and the 2D TOF or 2D PC-MRA
      technique for venous evaluation. For the evaluation of aneurysms and
      arteriovenous malformations (AVMs), we recommend the 3D CE-MRA technique,
      especially dynamic sequences in case of AVM. In this review, the technical
      aspects, limitations, and optimization of these MRA techniques will be discussed
      together with their indications in intracranial disease.

PMID- 15580490
TI  - Endovascular treatment of the posterior inferior cerebellar artery aneurysms.
AB  - Aneurysms may arise at various locations along the course of the posterior
      inferior cerebellar artery. Brainstem and cranial nerves manipulation make the
      surgical approach to proximal aneurysms difficult, while the occlusion of the
      parent vessel is sometimes unavoidable in peripheral aneurysms. Endovascular
      treatment can be a good alternative, but also with this approach the location of
      the aneurysm is critical. If occlusion of the parent vessel is planned,
      anatomical variations and vascular territories of the brainstem should be
      considered. We report our experience with 18 consecutive aneurysms (12 proximal,
      6 peripheral) treated by coils. Complete occlusion was achieved in 14 patients
      and subtotal in 4. In three patients the parent vessel had to be sacrificed.
      During treatment two perforations occurred; aneurysms were completely occluded
      without clinical consequences. Two small asymptomatic cerebellar infarctions were
      seen on postoperative computed tomography. Clinical outcome was good in 16
      patients.

PMID- 15580491
TI  - Randomized comparison of intra-arterial and intravenous thrombolysis in a canine
      model of acute basilar artery thrombosis.
AB  - We compared the rates of recanalization cerebral infarct and hemorrhage between
      intra-arterial (i.a.) reteplase and intravenous (i.v.) alteplase thrombolysis in
      a canine model of basilar artery thrombosis. Thrombosis was induced by injecting
      a clot in the basilar artery of 13 anesthetized dogs via superselective
      catheterization. The animals were randomized in a blinded fashion, 2 h after clot
      injection and verification of arterial occlusion, to receive i.v. alteplase 0.9
      mg/kg over 60 min and i.a. placebo, or i.a. reteplase 0.09 units/kg over 20 min,
      equivalent to one-half the alteplase dose, and i.v. placebo. Recanalization was
      studied for 6 h after treatment with serial angiography; the images were later
      graded in a blinded fashion. Blinded interpretation of postmortem MRI was
      performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h
      after initiation of treatment, partial or complete recanalization was observed in
      one of six dogs in the i.v. alteplase group and in five of seven in the i.a.
      reteplase group (P = 0.08). At 6 h, no significant difference in partial or
      complete recanalization was observed between the groups (two of six vs. five of
      seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated
      with i.v. alteplase and three of seven treated with i.a. reteplase (P = 0.4).
      Intracerebral hemorrhage was more common in the i.v. alteplase group (four of six
      vs. none of seven; P = 0.02). This study thus suggests that i.a. thrombolysis
      affords a recanalization rate similar to that of i.v. thrombolysis, but with a
      lower rate of intracerebral hemorrhage.

PMID- 15580492
TI  - Value of petrosal sinus sampling: coexisting acromegaly, empty sella and
      meningioma.
AB  - Simultaneous occurrence of an intracranial meningioma and a growth hormone (GH)
      producing pituitary adenoma is exceedingly rare, as is coexistence of an empty
      sella and acromegaly. We report all these rare entities in the same patient. We
      evaluated the role of inferior petrosal sinus sampling for lateralisation of an
      adenoma in this patient.

PMID- 15580493
TI  - The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in
      Korean population with allergic rhinitis.
AB  - The eotaxin gene family (eotaxin, eotaxin-2 and eotaxin-3) has been implicated in
      the recruitment of eosinophils, basophiles and Th2 lymphocytes that are central
      aspects of allergic diseases. To determine whether single-nucleotide
      polymorphisms (SNPs) of the eotaxin-2 and eotaxin-3 genes are associated with
      susceptibility to allergic rhinitis, we scanned 178 allergic rhinitis patients
      and 281 controls without allergic rhinitis using the direct sequencing and single
      base extension (SBE) methods. We also calculated the haplotype frequencies
      between +179T>C and +275C>T of eotaxin-2 and +2497T>G of eotaxin-3 in both
      controls and allergic rhinitis patients. The haplotype frequency between controls
      and allergic rhinitis patients was suggestively associated (P=0.0001). The
      genotype frequencies of eotaxin-3 +2497T>G in allergic rhinitis patients were
      suggestively different from those in non-allergic rhinitis controls (P=<0.0007).
      Our results strongly suggest that the SNP of eotaxin-3 might be associated with
      susceptibility to allergic rhinitis.

PMID- 15580494
TI  - Quantification of supplemental enzymes in animal feedingstuffs by radial enzyme
      diffusion.
AB  - Methods are described which facilitate quantification of supplemental cellulase,
      protease and alpha-amylase when added to animal feedingstuffs at normal
      industrial inclusion levels. The methods entail extraction of the enzymes from
      the feedingstuffs by agitation in buffer followed by quantification of extract
      activity using radial diffusion techniques. A linear relationship between the
      diameter of the zone of hydrolyzed substrate and the log of the enzyme activity
      applied is observed over a broad activity range. Assay of a feedingstuff
      supplemented with 1 kg t(-1) cellulase, protease and alpha-amylase yielded net
      supplemental activity recoveries of 104+/-11.7%, 91.3+/-6.74% and 126+/-29.5%,
      respectively. A similar assay method did not prove sufficiently sensitive to
      facilitate detection of xylanase at typical in-feed inclusion levels. The levels
      of endogenous cellulase, protease and alpha-amylase activity detected in the
      unsupplemented feedingstuffs were equivalent to 6.4+/-0.47%, 6.6+/-0.82% and
      29.0+/-14.1%, respectively, of a 1 kg t(-1) supplement. The methods are
      technically straightforward and will facilitate determination of enzyme
      stabilities during processes such as high-temperature pelleting of feedingstuffs,
      as well as allowing more rigorous quality control related to enzyme-supplemented
      animal feedingstuffs.

PMID- 15580495
TI  - Therapeutic insulins and their large-scale manufacture.
AB  - Biotechnological innovations over the past 25 years have underpinned the rapid
      development of a thriving biopharmaceutical sector. Therapeutic insulin remains
      one of the most commonly used products of pharmaceutical biotechnology and
      insulin-based products command annual global sales in excess of $4.5 billion.
      Innovations in its method of production and in particular the advent of
      engineered insulin analogues provide a fascinating insight into how scientific
      and technological advances have impacted upon the pharmaceutical biotechnology
      sector as a whole. Current insulin-based diabetes research is increasingly
      focused not on the insulin molecule per se, but upon areas such as the
      development of non-parenteral insulin delivery systems, as well as organ-/cell
      based and gene therapy-based approaches to controlling the disease.

PMID- 15580499
TI  - Spontaneous T-cell responses against peptides derived from the Taxol resistance
      associated gene-3 (TRAG-3) protein in cancer patients.
AB  - Expression of the cancer-testis antigen Taxol resistance-associated gene-3 (TRAG
      3) protein is associated with acquired paclitaxel (Taxol) resistance, and is
      expressed in various cancer types; e.g., breast cancer, leukemia, and melanoma.
      Thus, TRAG-3 represents an attractive target for immunotherapy of cancer. To
      identify HLA-A*02.01-restricted epitopes from TRAG-3, we screened cancer patients
      for spontaneous cytotoxic T-cell responses against TRAG-3-derived peptides. The
      TRAG-3 protein sequence was screened for 9mer and 10mer peptides possessing HLA
      A*02.01-binding motifs. Of 12 potential binders, 9 peptides were indeed capable
      of binding to the HLA-A*02.01 molecule, with binding affinities ranging from
      strong to weak binders. Subsequently, lymphocytes from cancer patients (9 breast
      cancer patients, 12 melanoma patients, and 13 patients with hematopoietic
      malignancies) were analyzed for spontaneous reactivity against the panel of
      peptides by ELISpot assay. Spontaneous immune responses were detected against 8
      epitope candidates in 7 of 9 breast cancer patients, 7 of 12 melanoma patients,
      and 5 of 13 patients with hematopoietic malignancies. In several cases, TRAG-3
      specific CTL responses were scattered over several epitopes. Hence, no
      immunodominance of any single peptide was observed. Furthermore, single-peptide
      responses were detected in 2 of 12 healthy HLA-A2(+) donors, but no responses
      were detectable in 9 HLA-A2(-) healthy donors or 4 HLA-A2(-) melanoma patients.
      The identified HLA-A*02.01-restricted TRAG-3-derived epitopes are targets for
      spontaneous immune responses in breast cancer, hematopoietic cancer, and melanoma
      patients. Hence, these epitopes represent potential target structures for future
      therapeutic vaccinations against cancer, possibly appropriate for strategies that
      combine vaccination and chemotherapy; i.e., paclitaxel treatment.

PMID- 15580500
TI  - Epidemiology of humeral fractures in Malawi.
AB  - We analysed and determined retrospectively the location, age, gender and side of
      the body of humeral fractures from 258 antero-posterior radiographs of all
      patients aged 3-81 years over a 5-year period. It was observed that 160 fractures
      occurred on the left side while 98 were on the right side with 156 occurring in
      males and 102 in females. Forty-eight percent of the fractures occurred at the
      lower end of the humerus while 41% occurred at the mid-shaft with only 10%
      occurring at the upper end. Furthermore, the age group of 3-12 years had the
      highest incidence of fractures (40.7%) with the age group of 30-39 years the
      lowest incidence (6.2%). Most supracondylar fractures (75.4%) occurred in
      children, with teenagers accounting for the majority of mid-shaft fractures
      (51.9%). However, middle-aged and elderly individuals had the highest incidence
      of upper humeral fractures (73.1%). There was significant relationship between
      the site of these fractures, age, gender and body side of the patients studied
      (p<0.001). These results are, however, not in agreement with some previously
      documented studies. The importance of epidemiological study of humeral fractures
      in planning, training and resource management in a given population is therefore
      stressed.

PMID- 15580501
TI  - Acute renal failure due to tumor lysis syndrome in a patient with non-Hodgkin's
      lymphoma.
AB  - Tumor lysis syndrome is characterized by multiple metabolic derangements
      resulting from the release of intracellular components into the bloodstream due
      to abrupt malignant cell death, spontaneously or following antineoplastic
      therapy. The syndrome is characterized by hyperkalemia, hyperuricemia,
      hyperphosphatemia, and hypocalcemia, while deposition of uric acid and calcium
      phosphate crystals may result in acute renal failure, which is often exacerbated
      by concomitant intravascular volume depletion. A case of tumor lysis syndrome
      complicated by acute renal failure in a patient with non-Hodgkin's lymphoma is
      reported and the pathophysiology, the clinical features, and the treatment
      options are discussed.

PMID- 15580502
TI  - Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic
      derangements associated with intravenous busulfan vs oral busulfan in adults
      conditioned with busulfan + cyclophosphamide for allogeneic bone marrow
      transplantation.
AB  - We investigated the occurrence of hepatic veno-occlusive disease (VOD) after
      allogeneic bone marrow transplantation (BMT) in 241 adults conditioned with
      busulfan + cyclophosphamide at a single institute and retrospectively compared
      186 patients who received oral busulfan (O-Bu group) with 55 patients who
      received intravenous busulfan (I-Bu group). Various hemostatic parameters were
      determined at baseline and on days 0, 7, 14, and 21. Hepatic VOD occurred in
      41.7% of the O-Bu group and in 18.5% of the I-Bu group. Multivariate analysis
      revealed that the I-Bu group had significantly decreased risk of VOD compared to
      the O-Bu group [p=0.006, odds ratio: (OR) 0.345]. Eleven patients in the O-Bu
      group and none of the I-Bu group developed severe VOD. A repeated measures
      analysis of variance (ANOVA) with a between-subjects factor revealed significant
      differences in post-transplant levels of antithrombin III, tissue plasminogen
      activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and D-dimer according
      to the occurrence of VOD. The level of antithrombin III was significantly lower,
      whereas the level of D-dimer was significantly higher, in the O-Bu group than in
      the I-Bu group. These findings show that, in adults conditioned with busulfan +
      cyclophosphamide, intravenous busulfan was associated with significantly
      decreased incidence of VOD and fewer hemostatic derangements after allogeneic BMT
      compared to oral busulfan.

PMID- 15580504
TI  - Plasma pharmacokinetics and tissue distribution of the breast cancer resistance
      protein (BCRP/ABCG2) inhibitor fumitremorgin C in SCID mice bearing T8 tumors.
AB  - Multidrug resistance (MDR) remains a major obstacle in the treatment of human
      cancers. The recently discovered breast cancer resistance protein (BCRP/ABCG2)
      has been found to be an important mediator of chemotherapeutic MDR. Fumitremorgin
      C (FTC) is a selective and potent inhibitor of BCRP that completely inhibits and
      reverses BCRP-mediated resistance at micromolar concentrations. We report a study
      of the pharmacokinetics and tissue distribution of FTC when administered
      intravenously (IV) at a dose of 25 mg/kg to female SCID mice bearing the BCRP
      overexpressing human ovarian xenograft Igrov1/T8 tumors. Plasma pharmacokinetics
      and tissue distribution of FTC in various organs and tissues were studied. In
      addition, the effect of FTC administration on the expression of BCRP in T8 tumors
      was also assessed by RT-PCR. Administration of a single FTC IV dose did not
      appear to cause any major toxicities. The resulting pharmacokinetic data were fit
      to a two-compartment model using NONMEM and the FTC clearance was determined to
      be 0.55 ml/min (25.0 ml/min/kg) with a 56% inter-animal variability. Area under
      the plasma concentration time curve was determined by Bailer's method and was
      calculated to be 1128+/-111 microg min/ml. FTC was widely distributed in all
      tissues assayed with highest concentrations found in lungs, liver and kidney in
      decreasing order, respectively. FTC did not appear to have any effect on the
      expression of BCRP in T8 tumors. Less than 2% of the administered dose was
      recovered in the urine and feces after 24 h, suggesting hepatic metabolism as a
      primary mechanism of elimination. The current study can be used as a basis for
      future animal or in vivo studies with FTC designed to further understand the
      impact of BCRP on drug resistance.

PMID- 15580505
TI  - [Solid pseudopapillary neoplasms. Enigmatic entity with female preponderance].
AB  - Solid pseudopapillary neoplasms (SPN) of the pancreas represent a special tumor
      entity, both morphologically and biologically. They form large solitary tumors
      that occur predominantly in young women. Histologically, they show solid,
      pseudopapillary, and pseudocystic patterns. The tumor cells are monomorphous and
      typically express vimentin, neuron-specific enolase, nuclear beta-catenin, and
      the progesterone receptor. Complete resection cures the tumor in about 90% of the
      cases. However, because recurrences and even metastases may occur in a small
      number of cases, SPN are classified as low-grade malignant tumors. Predicting
      malignancy histologically is not yet possible. The most important differential
      diagnosis to consider is neuroendocrine tumor of the pancreas. The etiology and
      pathogenesis of SPN are obscure.

PMID- 15580506
TI  - Hysterosalpingography with gadolinium.
AB  - We report a case of diagnostic hysterosalpingography performed using gadoteric
      acid (1,350 mOsm) in a patient with a prior severe generalized adverse reaction
      to iodinated contrast media.

PMID- 15580507
TI  - Transarterial chemoembolization alone and in combination with other therapies: a
      comparative study in an animal HCC model.
AB  - The purpose of this study is to compare transarterial chemoembolization (TACE)
      alone and in combination with other therapies in an animal model. Subcapsular
      implantation of a solid Morris hepatoma 3924A in the liver was carried out in 50
      male ACI rats (day 0). Tumor volume (V1) was measured by MRI (day 13). After
      laparotomy and retrograde placement of a catheter into the gastroduodenal artery
      (day 14), the following protocols of the interventional procedure were applied:
      TACE (mitomycin C + lipiodol) + immunotherapy (group A: TNFalpha + IL-2, group B:
      OK-432 + IL-2); TACE + antiangiogenesis therapy (group C: TNP-470, group D:
      endostatin); TACE alone in group E (control group). Tumor volume (V2) was
      assessed by MRI and the mean ratio of x (V2/V1) was calculated. Data were
      analyzed using Dunnett's t test (comparing therapeutic groups with the control
      group) and the Student-Newman-Keuls test (comparing significant therapeutic
      groups). Multivariate analysis showed a significant reduction in the tumor growth
      rate (P<0.05) in groups B (x=6.53) and C (x=4.01) compared to the mean ratio of
      the control group E (x=9.14). Significant results were observed in group C
      (P<0.05) in comparison with the other therapeutic groups. TACE combined with
      immunotherapy (OK-432) and antiangiogenesis therapy (TNP-470) retards tumor
      growth compared with TACE alone in an HCC animal model.

PMID- 15580508
TI  - Propofol attenuates reperfusion injury after testicular torsion and detorsion.
AB  - Propofol, which is widely used as an intravenous anesthetic, has been shown to
      have an antioxidant activity on several tissues. This study was designed to
      investigate the prevention of reperfusion injury with propofol after testicular
      torsion. Five groups of rats (seven in each group) were used. Animals in the
      control group (group I) did not received any treatment, while animals in the sham
      group (group II) underwent scrotal incision and testicular fixation only. After 2
      h of 720 degrees left testicular torsion in groups III, IV and V, subsequent
      detorsion was done for 2 h in groups IV and V. Propofol (50 mg/kg) was injected
      transperitoneally 30 min prior to detorsion in group V. Both testicles in all
      rats were retrieved and tissue malondialdeyhde (MDA) level, which is a measure of
      the amount of free oxygen radicals, and enzymatic activity of xanthine oxidase
      (XO), which converts hypoxanthine to xanthine and uric acid were studied. In
      addition, tissue catalase (CAT) and glutathione peroxidase (GSH-Px) activities,
      which are endogenous scavenger enzymes, protecting tissues against free radicals,
      were studied. Additionally, histological evaluations were performed after
      hematoxylin and eosin staining. Testicular MDA levels, and XO and CAT activities
      were higher in the torsion group compared to sham control group (P<0.05).
      Detorsion caused a further increase in MDA levels, contrasting with a decrease in
      the levels of XO activity, while CAT activity was not changed. Pretreatment with
      propofol prevented a further increase in MDA levels and significantly decreased
      CAT activity following detorsion. GSH-Px activities were not effected either by
      torsion/detorsion or propofol pretreatment. Histologically, torsion caused some
      separation between germinal cells in the seminiferous tubules, which became much
      more prominent in the detorsion group and attenuated with propofol pretreatment.
      There was no significant change in any of the above-mentioned enzymatic
      activities nor were there histopathological changes in the contralateral testicle
      in any groups. It is concluded that biochemically and histologically reperfusion
      injury occurs in the ipsilateral testis following detorsion up to 2 h. Preference
      of propofol for anaesthesia during the detorsion procedure may attenuate such
      reperfusion injury.

PMID- 15580511
TI  - Adaptation of skull clamp for use in image-guided surgery of children in the
      first 2 years of life.
AB  - INTRODUCTION: We describe a simple but effective modification of the skull clamp,
      aimed at stabilising the head of very young children, while avoiding the risk of
      creating a depressed skull fracture, in order to enable the utilisation of image
      guidance in such young patients. METHODS: We machined three small perspex discs 3
      cm in diameter. On the outer surface of these pads we drilled reception holes for
      the pins to prevent slippage. To avoid direct contact with the skin, we
      interfaced a thick pad of soft felt. During intraoperative positioning, the
      weight of the head was supported by a suction bean-bag placed on the operating
      table. Hence, the clamp apparatus was employed only to secure the head position,
      and not to support the weight of the head, thus requiring less clamp force. We
      employed this modification in three children (aged 9, 13 and 15 months) who
      required image-guided surgery for brain tumours. OUTCOME: In all cases the head
      remained immobile throughout the operation, making possible the accurate use of
      image guidance. At the end of the operation, some transient skin redness was
      noticed in the contact areas, which settled in a few days.

PMID- 15580509
TI  - [Blunt ocular trauma. Part II. Blunt posterior segment trauma].
AB  - This review presents typical patterns of posterior segment injuries as well as
      diagnostic and therapeutic considerations after ocular contusion or rupture of
      the globe. Vitreal prolapse is associated with retinal detachment (20%),
      iridodialysis or ciliary body cleft (43%), and contusion cataract (41%). Berlin's
      edema (35%) and retinal detachment (5-7%) are frequent after ocular contusion. In
      cases of central Berlin's edema, choroidal infarction (Hutchinson-Siegrist
      Neubauer syndrome) or choroidal rupture, macular hole or choroidal
      neovascularization should be ruled out. A central choroidal rupture is often
      associated with choroidal neovascularization (14-20%). Globe ruptures (5% of
      blunt injuries) are associated with hyphema grades III and IV (58 vs 5% in ocular
      contusions). The prognosis of globe ruptures to develop a visual function <20/200
      is 51 times more frequent than in eyes with contusion. The risk of trauma-induced
      globe ruptures is higher in eyes after cataract surgery (27 x) (in females 5 x).

PMID- 15580512
TI  - Secondary infection of intracranial hydatid cyst with Clostridium ramosum.
AB  - INTRODUCTION: Brain involvement in hydatid disease occurs in 1-2% of all
      Echinococcus granulosus infections. Secondary infection of intracranial hydatid
      cysts is extremely rare. CASE REPORT AND DISCUSSION: In this case report, we
      present a secondary infection of an intracranial hydatid cyst due to Clostridium
      ramosum, which is an extremely rare infectious pathogen in neurosurgical
      practice, and a potential pitfall in neuroradiological investigations.

PMID- 15580513
TI  - Age-related differences in intracranial pressure and cerebral perfusion pressure
      in the first 6 hours of monitoring after children's head injury: association with
      outcome.
AB  - OBJECTIVES: Severe head injury in childhood is associated with considerable
      mortality and morbidity. In this study we determined age-related differences in
      the relationship between outcome and intracranial pressure (ICP) and cerebral
      perfusion pressure (CPP) in the first 6 h of monitoring in a large cohort of head
      injured children. METHODS: Two hundred and thirty-five head-injured children
      (admitted to five UK hospitals over a 15-year period) in whom intracranial
      pressure monitoring was clinically indicated were studied. RESULTS: Patients were
      divided into three age groups (2-6, 7-10 and 11-16 years). The sensitivity of ICP
      and CPP were similar. Differences were found in the specificity of ICP and CPP
      for each group and these were more marked for CPP. For a specificity of 50% the
      pressures were 53, 63 and 66 mmHg for the three age groups. CONCLUSIONS: There
      are age-related differences in the specificity of intracranial pressure and
      cerebral perfusion pressure in relation to outcome. These differences may be
      important in the clinical management of head-injured children. Thus cerebral
      perfusion pressures of 53, 63 and 66 mmHg should be the minimum to strive for in
      these three age groups respectively.

PMID- 15580514
TI  - Hand somatosensory cortex activity following selective dorsal rhizotomy: report
      of three cases with fMRI.
AB  - INTRODUCTION: Selective dorsal rhizotomy (SDR) is an effective treatment for
      lower extremity spasticity in cerebral palsy. Cortical organization in sensory
      cortex may be abnormal in cerebral palsy, and deafferentation is known to lead to
      cortical reorganization in many situations. METHODS: We used functional magnetic
      resonance imaging (fMRI) of hand sensory stimulation to determine if the partial
      deafferentation of the lower extremity sensory system, associated with SDR, led
      to any alterations in the cortical somatosensory representation for the upper
      limbs. Three patients with spastic diplegia were studied with blood oxygen level
      dependent (BOLD)-fMRI before and after SDR. fMRI during tactile stimulation of
      the digits of the right hand was used to map hand somatosensory cortex.
      Comparison of the cortical maps devoted to the hand before and after SDR assessed
      for cortical reorganization following partial deafferentation of the lower
      extremity. RESULTS: In the one patient with upper extremity involvement, the hand
      sensory representation was markedly enhanced following SDR. In the other two
      patients, a normal pattern, but with diminished activity, was seen compared with
      preoperative findings. SDR for lower limb spastic diplegia does not lead to
      extensive reorganization of cortex dedicated to the representation of the upper
      limb. An essentially normal pattern of activation was seen both before and after
      SDR. CONCLUSION: The relief of attention demands associated with spasticity may
      explain the modulation in intensity seen after SDR in the patients who exhibited
      no upper extremity involvement despite lower limb spasticity.

PMID- 15580515
TI  - Neurocutaneous melanosis with associated Dandy-Walker complex.
AB  - CASE REPORT: The authors report the case of a child with neurocutaneous melanosis
      associated with a Dandy-Walker complex. Magnetic resonance (MR) images showed
      shortened T1-weighted images in areas involving the amygdala, mesencephalon,
      rostral brain stem, and superior cerebellar surface compatible with melanin
      deposits. There was also partial agenesis of the cerebellar vermis with an
      enlarged fourth ventricle cyst along with a high-lying torcular and ventricular
      enlargement. Endoscopic fenestration and biopsy of the cyst wall was performed
      without evidence of abnormal melanin deposits in the meninges. OUTCOME: The
      patient eventually required ventriculoperitoneal shunting and at 1-year follow-up
      did not develop evidence of primary CNS melanoma. ILLUSTRATION: Computed
      tomography and MR images consistent with neurocutaneous melanosis and the Dandy
      Walker complex are presented along with photographs of the cutaneous nevi.
      DISCUSSION: The major clinical and radiological features of this rare
      association, with only 11 previously reported cases, are discussed in detail.

PMID- 15580516
TI  - Possible spontaneous "birth" of a hydatid cyst into the lateral ventricle.
AB  - INTRODUCTION: Intraventricular hydatid cyst is an extremely rare entity. We
      report a solitary hydatid cyst in a lateral ventricle. CASE REPORT: A 7-year-old
      girl had a free floating intraventricular cyst, diagnosed by computerized
      tomography examination inside the enlarged left lateral ventricle of an
      associated Dandy Walker malformation. The patient underwent surgery and the cyst
      was removed. CONCLUSION: To our knowledge, this is the first case report in which
      the natural developmental phases of an intraventricular hydatid cyst have been
      observed.

PMID- 15580517
TI  - Progressive loss of myocardial contractile function despite unimpaired coronary
      blood flow after cardiac surgery.
AB  - OBJECTIVE: Mild to moderate transient contractile dysfunction is frequently
      observed after cardiac surgery on cardiopulmonary bypass (CPB) but may also lead
      to low-cardiac-output (LCO) failure especially in patients with unstable angina,
      and is often referred to represent myocardial stunning. Whether time course of
      contractile dysfunction after cardiac surgery is similar to that of myocardial
      stunning was investigated in pigs. METHODS: After baseline measurements of
      systemic hemodynamics (micromanometry), myocardial contractile function
      (sonomicrometry), cardiac output and coronary flow (ultrasonic probe), CPB was
      instituted. Control animals (n = 7) were weaned after 3 h from CPB. In LCO
      animals (n = 8), global ischemia was induced for 10 min by aortic crossclamping,
      followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion,
      CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4
      h and 8 h after CPB. Systemic TNFalpha-plasma concentrations were measured
      (ELISA) and left ventricular biopsies were analyzed with respect to myocardial
      TNFalpha (immunohistochemistry) and irreversible cellular damage (light/electron
      microscopy). RESULTS: Contractile function decreased in LCO (75 +/- 12%) and
      control (83 +/-17%) at 15 min compared to baseline (p < 0.05). Thereafter,
      contractile function remained unchanged in control, but progressively decreased
      in LCO (52 +/- 12% at 4 h; 36 +/- 5% at 8 h; p < 0.05). Coronary flow remained
      unchanged in both groups. Cardiac output progressively decreased to 2.8 +/- 0.9
      l/min at 8 h in the LCO group compared to baseline (5.9 +/- 1.1 l/min, p < 0.05)
      and control (5.7 +/- 1.4 l/min, p < 0.05). There was no evidence for myocardial
      infarction. TNFalpha-plasma concentrations and myocardial TNFalpha-staining were
      increased at 8 h after CPB in the LCO group compared to baseline and control (p <
      0.05). CONCLUSIONS: The progressive pattern of myocardial dysfunction apart from
      ongoing ischemia after cardiac surgery suggested underlying mechanisms at least
      partially different from those of myocardial stunning.

PMID- 15580519
TI  - Expression and subcellular localization of Spred proteins in mouse and human
      tissues.
AB  - Spred-1 and Spred-2 (Sprouty-related protein with an EVH1 domain) are recently
      described members of the EVH1 (Ena/VASP-homology domain 1) family. Both Spred-1
      and Spred-2 are membrane-associated substrates of receptor tyrosine kinases and
      they act as negative regulators of the Ras pathway upon growth factor
      stimulation. Since the Spred family members seem to exert overlapping molecular
      functions, the isotype-specific function of each member remains enigmatic. To
      date, no comprehensive expression profiling of Spred proteins has been shown.
      Therefore, we compared mRNA and protein expression patterns of Spred-1 and Spred
      2 systematically in mouse organs. Furthermore, we focused on the tissue-specific
      expression of Spred-2 in adult human tissues, the subcellular localization, and
      the potential role of Spred-2 in the organism. Our studies show that expression
      patterns of Spred-1 and Spred-2 differ markedly among various tissues and cell
      types. In mouse, Spred-1 and Spred-2 were found to be expressed predominantly in
      brain, whereas Spred-2 was found to be more widely expressed in various adult
      tissues than Spred-1. In humans, Spred-2 was found to be strongly expressed in
      glandular epithelia and, at the subcellular level, its immunoreactivity was
      associated with secretory vesicles. Using confocal microscopy we found Spred-2 to
      be strongly colocalized with Rab11 and, to a lesser extent, with Rab5a GTPase, an
      observation that was not made for Spred-1. We conclude that the two members of
      the recently discovered Spred protein family, Spred-1 and Spred-2, show a highly
      specific expression pattern in various tissues reflecting a specific
      physiological role for the individual Spred isoforms in these tissues.
      Furthermore, it becomes most likely that Spred-2 is involved in the regulation of
      secretory pathways.

PMID- 15580520
TI  - Velocity at V(.)O(2 max) and peak treadmill velocity are not influenced within or
      across the phases of the menstrual cycle.
AB  - Velocity at VO(2 max) (vV(.)O(2 max)) and peak treadmill velocity (PTV) are
      variables highly predictive of endurance performance. However, how these
      variables are affected by the menstrual cycle is unknown. The aim of this study
      was to assess the effect of the menstrual cycle on vV(.)O(2 max) and PTV. Ten,
      female runners were studied across three menstrual cycles. Training, menstrual
      history and mood states were assessed for 2 months, with daily salivary samples
      taken to detect menstrual phases. During the third menstrual cycle, participants
      completed a maximal test to determine V(.)O(2 max), vV(.)O(2 max) and PTV in the
      early follicular phase, late follicular phase, early luteal phase, late luteal
      phase and menses. Progesterone increased at the onset of the luteal phase [mean
      (SEM); 490 (73.6) pmol l(-1)] compared to the follicular phase [344.6 (59.7) pmol
      l(-1)). No significant differences in the psychological mood states between the
      phases of the menstrual cycle were found (P>0.05). No significant differences in
      vV(.)O(2 max) (P=0.611), or PTV (P=0.472) were found between the phases of the
      menstrual cycle. Thus, vV(.)O(2 max) and PTV are not affected by the monthly
      menstrual cycle in female endurance runners.

PMID- 15580521
TI  - Characterisation, asymmetry and reproducibility of on- and off-transient
      pulmonary oxygen uptake kinetics in endurance-trained runners.
AB  - The purpose of this study was three-fold: (1) to characterise both the on- and
      off-transient oxygen uptake (V(.)O(2)) kinetics in endurance runners during
      moderate-intensity treadmill running; (2) to determine the degree of symmetry
      between on- and off-transients; and (3) to determine the reproducibility of
      V(.)O(2) kinetic parameters in endurance runners. Twelve endurance-trained
      runners [mean (SD) age 25.2 (4.7) years, body mass 70.1 (9.7) kg, height 179.5
      (7.5) cm, ventilatory threshold (V(T)), 3,429 (389) ml.min(-1), maximal V(.)O(2)
      (V(.)O(2max)) 4,138 (625) ml.min(-1)] performed two multiple square-wave
      transition protocols on separate days. The protocol consisted of six (three
      transitions, 15 min rest, three transitions) square-wave transitions from walking
      at 4 km.h(-1) to running at a speed equivalent to 80% of the V(.)O(2) at the V(T)
      (80%V(T)). To determine the reproducibility, the protocol was repeated on a
      separate day (i.e. a test-retest design). Pulmonary gas-exchange was measured
      breath-by-breath. The V(.)O(2) data were modelled [from 20 s post-onset (or
      offset) of exercise] using non-linear least squares regression by a mono
      exponential model, incorporating a time delay. The on- and off-transient time
      constants (tau(on) and tau(off)), mean response times (MRT(on) and MRT(off)) and
      amplitudes (A(on) and A(off)) were obtained from the model fit. On- and off
      transient kinetics were compared using paired t-tests. The reproducibility of
      each kinetic parameter was explored using statistical (paired t-tests) and non
      statistical techniques [95% limits of agreement (LOA, including measurement error
      and systematic bias) and coefficient of variation (CV)]. It was found that the
      tau(on) [12.4 (1.9)] was significantly (P<0.001) shorter than tau(off) [24.5
      (2.3) s]. Similarly, MRT(on) [27.1 (1.9) s] was shorter than MRT(off) [33.4 (2.2)
      s]. With respect to the reproducibility of the parameters, paired t-tests did not
      reveal significant differences between test 1 and test 2 for any on- or off
      transient V(.)O(2) kinetic parameter (P>0.05). The LOA for tau(on) (1.9 s),
      tau(off) (2.3 s), MRT(on) (1.2 s), MRT(off) (3.2 s), A(on) (204 ml.min(-1)) and
      A(off) (198 ml.min(-1)) were narrow and acceptable. Furthermore, the measurement
      error (range, 4.3 to 15.1%) and CV (1.3 to 4.8%) all indicated good
      reproducibility. There was a tendency for tau(off) to be more reproducible than
      tau(on). However, MRT(on) was the most reproducible kinetic parameter. Overall,
      the results suggest that: (1) a multiple square-wave transition protocol can be
      used to characterise, reproducibly, both on- and off-transient V(.)O(2) kinetic
      parameters during treadmill running in runners; (2) the phase II time constant is
      independent of V(.)O(2) (max), and (3) asymmetry exists between on- and off
      transient V(.)O(2) kinetic parameters.

PMID- 15580522
TI  - Modeling of a bipedal robot using mutually coupled Rayleigh oscillators.
AB  - The objective of the work presented here was the modeling of a bipedal robot
      using a central pattern generator (CPG) formed by a set of mutually coupled
      Rayleigh oscillators. We analyzed a 2D model, with the three most important
      determinants of gait, that performs only motions parallel to the sagittal plane.
      Using oscillators with integer relation of frequency, we determined the transient
      motion and the stable limit cycles of the network formed by the three
      oscillators, showing the behavior of the knee angles and the hip angle. A
      comparison of the plotted graphs revealed that the system provided excellent
      results when compared to experimental analysis. Based on the results of the
      study, we come to the conclusion that the use of mutually coupled Rayleigh
      oscillators can represent an excellent method of signal generation, allowing
      their application for feedback control of a walking machine.

PMID- 15580523
TI  - Use of bone anchors in perineal hernia repair: a practical note.
AB  - BACKGROUND: Bone anchoring systems are used extensively in orthopaedic surgery
      but have scarcely been reported as useful in abdominal wall or perineal hernia
      repair. After coccygectomy or sacrectomy the development of bowel herniation is
      not uncommon. Considering repair of such a perineal hernia, adequate fixation of
      the prosthetic mesh is difficult and, therefore, recurrence is rather frequent,
      mostly due to insufficient anchoring of the mesh to the bony structures. METHODS:
      We discuss a patient in which the Mitek GII anchoring system was used to overcome
      the problem of soft-tissue-to-bone attachment in such cases. CONCLUSION: Bone
      anchoring systems seem to be an efficient method to overcome the problems of soft
      tissue-to bone attachment in both abdominal and perineal hernia repair.

PMID- 15580524
TI  - High salinity reduces the content of a highly abundant 23-kDa protein of the
      mangrove Bruguiera parviflora.
AB  - A significant decrease in the amount of a protein, whose migration in two
      dimensional gel electrophoresis corresponds to an apparent molecular mass of 23
      kDa and pI = 6.5, was observed in leaves of NaCl-treated Bruguiera parviflora
      (Roxb.) Wt. & Arn. ex Griff. seedlings. This particular salt-sensitive protein,
      designated as SSP-23, almost disappeared after 45 days of treatment in 400 mM
      NaCl as compared to untreated seedlings (0 mM NaCl) where the presence of the
      protein was significant. A polyclonal antibody raised against the 23-kDa protein
      was used to determine the subcellular localization of this protein in leaves by
      cross-reaction with proteins from isolated chloroplasts, mitochondria,
      peroxisomes and cytosol fractions on Western blots. SSP-23 was confirmed to be
      localized in the cytosol by immunoblotting. The disappearance of SSP-23 as a
      result of high NaCl treatment suggests that this protein is salt-sensitive and
      has a possible role in salt adaptation.

PMID- 15580525
TI  - FTIR imaging of wheat endosperm cell walls in situ reveals compositional and
      architectural heterogeneity related to grain hardness.
AB  - Endosperm cell walls of cultivars of wheat (Triticum aestivum L.) selected for
      their endosperm texture (two soft and two hard) were analysed in situ by Fourier
      transform infrared (FTIR) microspectroscopy. FTIR imaging coupled with
      statistical analysis was used to map the compositional and structural
      heterogeneity within transverse sections from which cell contents had been
      removed by sonication. In the majority of grains analysed, two distinct
      populations of endosperm cells could be identified by spectral features that were
      related to cell morphology and age, regardless of cultivar. The main cell-wall
      component responsible for these differences was the polysaccharide arabinoxylan.
      In a few samples, this heterogeneity was absent, for reasons that are not
      understood, but this was not correlated to endosperm texture or growth
      conditions. Within the same population of endosperm cells, cell walls of hard
      endosperm could be distinguished from those of soft endosperm by their spectral
      features. Compared to hard cultivars, the peripheral endosperm of soft cultivars
      was characterised by a higher amount of polymer, whose spectral feature was
      similar to water-extractable arabinoxylan. In contrast, no specific compound has
      been identified in the central endosperm: structural differences within the
      polysaccharides probably contribute to the distinction between hard and soft
      cultivars. In developing grain, a clear difference in the composition of the
      endosperm cell walls of hard and soft wheat cultivars was observed as early as 15
      days after anthesis.

PMID- 15580526
TI  - Enhanced thermotolerance of photosystem II in salt-adapted plants of the
      halophyte Artemisia anethifolia.
AB  - Thermotolerance of photosystem II (PSII) in leaves of salt-adapted Artemisia
      anethifolia L. plants (100-400 mM NaCl) was evaluated after exposure to heat
      stress (30-45 degrees C) for 30 min. After exposure to 30 degrees C, salt
      adaptation had no effects on the maximal efficiency of PSII photochemistry
      (F(v)/F(m)), the efficiency of excitation capture by open PSII centers
      (F(v)'/F(m)'), or the actual PSII efficiency (Phi(PSII)). After pretreatment at
      40 degrees C, there was a striking difference in the responses of F(v)/F(m),
      F(v)'/F(m)' and Phi(PSII) to heat stress in non-salt-adapted and salt-adapted
      leaves. Leaves from salt-adapted plants maintained significantly higher values of
      F(v)/F(m), F(v)'/F(m)' and Phi(PSII) than those from non-salt-adapted leaves. The
      differences in F(v)/F(m), F(v)'/F(m)' and Phi(PSII) between non-salt-adapted and
      salt-adapted plants persisted for at least 12 h following heat stress. These
      results clearly show that thermotolerance of PSII was enhanced in salt-adapted
      plants. This enhanced thermotolerance was associated with an improvement in
      thermotolerance of the PSII reaction centers, the oxygen-evolving complexes and
      the light-harvesting complex. In addition, we observed that after exposure to
      42.5 degrees C for 30 min, non-salt-adapted plants showed a significant decrease
      in CO(2) assimilation rate while in salt-adapted plants CO(2) assimilation rate
      was either maintained or even increased to some extent. Given that photosynthesis
      is considered to be the physiological process most sensitive to high-temperature
      damage and that PSII appears to be the most heat-sensitive part of the
      photosynthetic apparatus, enhanced thermotolerance of PSII may be of significance
      for A. anethifolia, a halophyte plant, which grows in the high-salinity regions
      in the north of China, where the air temperature in the summer is often as high
      as 45 degrees C.

PMID- 15580527
TI  - Magnesium deficiency in sugar beets alters sugar partitioning and phloem loading
      in young mature leaves.
AB  - Magnesium deficiency has been reported to affect plant growth and biomass
      partitioning between root and shoot. The present work aims to identify how Mg
      deficiency alters carbon partitioning in sugar beet (Beta vulgaris L.) plants.
      Fresh biomass, Mg and sugar contents were followed in diverse organs over 20 days
      under Mg-sufficient and Mg-deficient conditions. At the end of the treatment, the
      aerial biomass, but not the root biomass, of Mg-deficient plants was lower
      compared to control plants. A clear inverse relationship between Mg and sugar
      contents in leaves was found. Mg deficiency promoted a marked increase in sucrose
      and starch accumulation in the uppermost expanded leaves, which also had the
      lowest content of Mg among all the leaves of the rosette. The oldest leaves
      maintained a higher Mg content. [14C]Sucrose labelling showed that sucrose export
      from the uppermost expanded leaves was inhibited. In contrast, sucrose export
      from the oldest leaves, which are close to, and export mainly to, the roots, was
      not restricted. In response to Mg deficiency, the BvSUT1 gene encoding a
      companion cell sucrose/H+ symporter was induced in the uppermost expanded leaves,
      but without further enhancement of sucrose loading into the phloem. The observed
      increase in BvSUT1 gene expression supports the idea that sucrose loading into
      the phloem is defective, resulting in its accumulation in the leaf.

PMID- 15580528
TI  - A stress-inducible plasma membrane protein 3 (AcPMP3) in a monocotyledonous
      halophyte, Aneurolepidium chinense, regulates cellular Na(+) and K(+)
      accumulation under salt stress.
AB  - Regulation of ion homeostasis is fundamental to physiological activities in
      plants. Here, we report on the functional characterization of AcPMP3
      [Aneurolepidium chinense (a monocotyledonous halophyte) plasma membrane protein
      3] under salt stress. Expression of AcPMP3-1 and AcPMP3-2 genes was highly
      induced by various abiotic stresses, such as salt, cold and drought. Furthermore,
      abscisic acid, H(2)O(2) and salicylic acid also triggered expression of AcPMP3
      genes. In the Deltanha1 Deltapmr2 Deltapmp3 yeast mutant, which lacks the major
      Na(+) efflux systems (Na(+)/H(+) antiporter and Na(+)-ATPase), its salt-sensitive
      phenotype was restored by expressing the AcPMP3-1 gene, and the transformants
      accumulated lesser amounts of Na(+) and K(+) than mutant cells under 50 mM NaCl
      and 500 mM KCl conditions, respectively. These results suggested that AcPMP3-1
      plays a role as a regulator of both Na(+) and K(+) accumulation in the cells. In
      situ hybridization showed that the AcPMP3-1 transcript was localized in cells of
      the root cap and root epidermis, which strongly suggested that AcPMP3-1 is
      essential for regulating Na(+)/K(+) transportation between plant roots and the
      outer environment under salt stress.

PMID- 15580529
TI  - Bidirectional links in the network of multiplication facts.
AB  - In three experiments, we tested the hypothesis that activation of multiplication
      operand nodes (e.g., 3 and 8) can occur through presentation of their product
      (e.g., 24). In Experiments 1 and 2 we found activation of the operands when the
      product was presented as a cue in a number-matching task. In Experiment 3,
      activation also occurred in a parity-matching task, where the product (24) was
      not relevant to the parity matching on its operands (3 and 8). We concluded that
      bidirectional links exist among the operands and their product for multiplication
      problems and these links can be activated in a purely stimulus-driven manner. We
      suggest this may constitute the basis for the solution of simple divisions by
      mediation through the complementary multiplication facts.

PMID- 15580530
TI  - Drosophila Bys is nuclear and shows dynamic tissue-specific expression during
      development.
AB  - Although the bys-like family of genes has been conserved from yeast to humans, it
      is not apparent to what extent the function of Bys-like proteins has been
      conserved across phylogenetic groups. Human Bystin is thought to function in a
      novel cell adhesion complex involved in embryo implantation. The product of the
      yeast bys-like gene, Enp1, is nuclear and has a role in pre-ribosomal RNA (pre
      rRNA) splicing and ribosome biogenesis. To gain insight into the function of the
      Drosophila melanogaster bys-like family member, termed bys, we examined bys mRNA
      expression and the localization of Bys protein. In embryos, bys mRNA is expressed
      in a tissue-specific pattern during gastrulation. In the larval wing imaginal
      disc, bys mRNA is expressed in the ventral and dorsal regions of the wing pouch,
      regions that give rise to epithelia that adhere to one another after the wing
      disc everts. The bys mRNA expression patterns could be interpreted as being
      consistent with a role for Bys in events requiring cell-cell interactions.
      However, embryonic bys mRNA expression patterns mirror those of genes that are
      potential targets of the growth regulator Myc and encode nucleolar proteins
      implicated in cell growth. Additionally, in Schneider line 2 (S2) cells, an
      epitope-tagged Bys protein is localized to the nucleus, suggesting that
      Drosophila Bys function may be conserved with that of yeast Enp1.

PMID- 15580531
TI  - [Commentary on the current immunotherapy of chronic inflammatory demyelinating
      polyneuropathy].

PMID- 15580532
TI  - [Immunotherapy of chronic inflammatory demyelinating polyneuropathy].
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune
      mediated disease of the peripheral nervous system with an estimated prevalence of
      1-2/100,000. The clinical presentation is heterogeneous, but the most common form
      causes symmetrical progressive or relapsing weakness affecting proximal and
      distal muscles. CIDP is among the most treatable peripheral nerve disorders and
      corticosteroids, plasmapheresis and intravenous immunoglobulin have been shown to
      be effective in short-term prospective, randomized controlled trials. Data
      however indicate that approximately one-third of patients do not respond to these
      treatment modalities, nor do they provide equivalent evidence for a durable
      clinical response. There is a lack of good quality controlled trials of any other
      immunosuppressive agent, but cyclophosphamide and cyclosporin may be of value in
      patients with poor response to first-line modalities. Alternatively, the use of
      combination therapy may increase the efficacy in unresponsive patients. This
      review highlights the current status of CIDP treatment trials and discusses the
      significance of any therapeutic option in terms of efficacy, tolerability and
      cost-effects.

PMID- 15580533
TI  - [AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related
      disorders].
AB  - Actually, guidelines for treatment of substance-related disorders were written
      under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears
      within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen
      Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines
      is the description of the current scientifically proven and evidence-based
      medicine in addiction to derive recommendations to therapy. In this context, the
      guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen
      related disorders is introduced.

PMID- 15580534
TI  - [Quality of guidelines for the treatment of alcohol related disorders -- a
      systematic review and content analysis].
AB  - BACKGROUND: Alcohol related disorders (dependent, harmful or at risk drinking)
      display a high prevalence in the community. We systematically reviewed and
      assessed the quality of available guidelines in the context of developing an
      evidence-based pathway of care for the treatment of those disorders in primary
      care. METHODS: We searched the internet for guidelines published in English,
      German, Italian, French or Spanish. The search was performed using the following
      sources: Internet Search engines, guideline providing agencies via internet,
      MEDLINE, PsychInfo and Cochrane Library. In addition, national professional
      societies were contacted to provide existing guidelines. We used a standardized
      instrument to assess methodological quality in three dimensions using dichotomous
      items: methodology of guideline development (21 items), content of guideline (17
      items) and application (6 items). Each guideline was evaluated independently by
      two reviewers (MB, SH). Disagreement was documented using a disagreement protocol
      and resolved by discussion. Results were expressed as percent of total (domain)
      score. RESULTS: We included 9 published guidelines and 2 drafts. The
      methodological quality was heterogeneous. The mean quality score was below 50 %
      of the maximum score. Major flaws were lack of clear grounding in evidence-based
      medicine, too much information provided, lack of consumer involvement or
      insufficient involvement of all care providers as well as lack of implementation
      strategies. The scores of the guidelines published by professional societies for
      primary care were higher than the others. DISCUSSION: As demonstrated by the
      identified guidelines, more interdisciplinary panels and evidence-based processes
      need to be incorporated in the development process of guidelines for the
      treatment of alcohol related disorders. Our findings suggest that it might be
      advisable and effective to adapt already available valid and evidence-based
      guidelines or to collaborate with international working groups for the
      development of guidelines. There is a strong need for the scientific evaluation
      of implementation processes.

PMID- 15580535
TI  - [Acute treatment of schizophrenia].

PMID- 15580537
TI  - A case of extreme unconjugated fetal hyperbilirubinemia.
AB  - We present an unusual case of severe unconjugated hyperbilirubinemia and normal
      hemoglobin at birth in a premature newborn with Rh incompatibility. We speculate
      that the possible mechanism is due to placental dysfunction. To our knowledge,
      this is the highest reported unconjugated bilirubin level at birth.

PMID- 15580538
TI  - Large vancomycin overdose in two premature infants with minimal toxicity.
AB  - Two premature infants received 10-fold overdoses of vancomycin with resulting
      peak plasma concentrations > 300 microg/mL. Discontinuation of vancomycin and
      watchful waiting were employed, with no specific intervention to accelerate
      vancomycin clearance. Plasma vancomycin concentration < 40 microg/mL was attained
      at < 48 hours in one infant and < 72 hours in the other. Although one infant
      sustained a transient increase in serum creatinine to 1.4 mg/dL, no further
      evidence of renal, auditory, or other toxicity was detected in either infant
      acutely or long term. Contemporary preparations of vancomycin appear much less
      toxic than earlier formulations. Aggressive and invasive interventions to hasten
      clearance may be unnecessary following overdose in infants with normal or near
      normal basal renal function, although careful surveillance for clearance and
      toxic effects still appear warranted.

PMID- 15580539
TI  - The origins and outcomes of triplet and quadruplet pregnancies in Nova Scotia:
      1980 to 2001.
AB  - The objective of this study was to determine the rate, origin, maternal and
      perinatal outcomes, and the associated hospital costs of higher order multiple
      births in one Canadian province. All higher order multiple pregnancies (triplets
      and above) in Nova Scotia over a 22-year period (1980 to 2001) were reviewed, and
      the maternal and perinatal outcomes and hospital costs were compared with
      singletons and twins in the same hospital population. During the 22-year period,
      116,785 infants were delivered, including 3448 twins, 99 triplets, and 16
      quadruplets. Of the higher order multiple gestations, 51.4% were conceived
      through infertility therapy. When compared with mothers of either singletons or
      twins, mothers of higher order gestations were significantly older, had longer
      antepartum and postpartum hospital stays, were more likely to have cesarean
      delivery, preterm labor, preeclampsia, and require intensive care unit admission.
      Triplets and quadruplets had significantly higher rates of preterm delivery,
      major anomalies, neonatal intensive care, respiratory distress syndrome,
      intrauterine growth restriction, serious morbidity, 5-minute Apgar scores < or =
      3, and neonatal death than twins or singletons. The estimated hospital costs for
      this population ranged from 6,750 US dollars for a singleton pregnancy to 278,400
      US dollars for a quadruplet pregnancy. Maternal morbidity, perinatal morbidity
      and mortality, and hospital costs are significantly increased in higher order
      births compared with both twins and singletons.

PMID- 15580540
TI  - Variables associated with successful vaginal birth after one cesarean section: a
      proposed vaginal birth after cesarean section score.
AB  - The objective of this study was to define the variables associated with vaginal
      birth after cesarean section (VBAC) and to develop a scoring system for the
      prediction of successful VBAC. We searched our computerized database for
      parturients with a history of one low-transverse cesarean section (CS) who were
      delivered during the year 2000. Variables were categorized according to the time
      period in which they were obtained: (1) first prenatal visit, (2) at the onset of
      labor, and (3) during labor. Univariate and multiple stepwise logistic regression
      models were fitted to calculate odds ratios (ORs) and 95% confidence intervals
      (CIs). Of the 475 parturients with a history of one previous CS, 136 underwent
      elective CS and 339 underwent a trial of VBAC, of whom 82% were successful. Of
      the variables that can be obtained at the onset of labor, five were significantly
      associated with successful VBAC: abnormal presentation as the indication for the
      primary CS (OR, 7.4; 95% CI 2.8 to 19.2), a previous VBAC (OR, 7.2; 95% CI, 2.1
      to 24.8), cervical dilation (OR, 2.5; 95% CI, 1.3 to 4.9), gestational age < or =
      41 weeks (OR, 2.8; 95% CI, 1.1 to 7.1), and lower gestational age at the primary
      CS (OR, 1.2; 95% CI, 1.02 to 1.4). In the proposed VBAC score, each of the four
      most significant variables was assigned a score ranging between 0 and 3 based on
      the probability for VBAC. A score < or = 2 was associated with a success rate of
      42%, a score between 3 and 6 was associated with a rate of 81%, and a score
      between 7 and 10 was associated with a 98% successful VBAC rate (p < 0001). The
      proposed VBAC score may help obstetricians when counseling their patients
      regarding the individual likelihood of a successful VBAC.

PMID- 15580541
TI  - Homeostatic model assessment and risk for hypertension during pregnancy: a
      longitudinal prospective study.
AB  - The purpose of this study was to determine the association between insulin
      resistance and hypertension during pregnancy with the homeostatic model
      assessment (HOMA-IR). A longitudinal prospective study was carried out. One
      hundred sixty normotensive pregnant women were followed from the first trimester
      until delivery. HOMA-IR levels were determined each trimester. Statistical
      analysis included one-way analysis of variance and multivariate logistic
      regression. At follow-up, 134 women (83.8%) remained normotensive, 18 (11.2%)
      developed gestational hypertension, and 8 (5%) developed preeclampsia. At first
      trimester, HOMA-IR levels were higher in women who developed gestational
      hypertension (2.1 +/- 0.2) than in women who developed preeclampsia (1.2 +/-
      0.0), or remained normotensive (1.2 +/- 0.3); p < 0.01. In the logistic
      regression analysis, HOMA-IR levels at first trimester were statistically
      significant ( p = 0.03) to predict development of gestational hypertension. Our
      results support the use of the HOMA-IR as an alternative index for the assessment
      of the risk for hypertension during pregnancy.

PMID- 15580542
TI  - Choledochal cyst diagnosed and conservatively treated during pregnancy.
AB  - We report herein a rare case of choledochal cyst diagnosed at 14 weeks gestation
      and treated with percutaneous transhepatic drainage until postpartum. A 26-year
      old primigravid woman at 14 weeks gestation presented with epigastric pain,
      slight fever, and nausea of 3 days duration. Abdominal ultrasonography revealed a
      6-cm-diameter cystic mass between the porta hepatis and the pancreas head, which
      was diagnosed as a type I choledochal cyst. At 18 weeks of gestation, her upper
      abdominal pain became severe, and the size of the choledochal cyst increased to
      12 cm in diameter. Laboratory data revealed a biliary obstruction. Percutaneous
      transhepatic drainage was performed immediately. She delivered a healthy male
      baby by elective cesarean section at 37 weeks of gestation. At 6 weeks
      postpartum, the patient underwent surgical excision of the choledochal cyst,
      cholecystectomy, and formation of a Roux-en-Y hepaticojejunostomy. Although
      choledochal cysts are rare during pregnancy, obstetricians should be familiar
      with the condition to ensure prompt diagnosis and adequate definitive management,
      given that the implications of missed or delayed diagnosis may be detrimental to
      both mother and fetus.

PMID- 15580543
TI  - The risk of folate and vitamin B(12) deficiencies associated with
      hyperhomocysteinemia among pregnant women.
AB  - The purpose of this study was to compare the folate and vitamin B (12) levels in
      pregnant and nonpregnant women to evaluate the risk for hyperhomocysteinemia and
      for folate and vitamin B (12) deficiencies during pregnancy. Healthy pregnant
      women (n = 92; 24 to 28 gestational weeks; 18 to 39 years old) and nonpregnant
      women (n = 176; 18 to 39 years old) were sampled for serum levels of folate,
      vitamin B (12), and homocysteine. Pregnant women were less likely to have folate
      deficiency (8.0% versus 12.0%) but much more likely to have vitamin B (12)
      deficiency (46.1% versus 0.6%) than nonpregnant women. Those with lower dietary
      vitamin intakes were more likely to have vitamin B (12) deficiency. Serum folate
      and vitamin B (12) were negatively correlated with homocysteine among pregnant
      women. Pregnant women with folate deficiency were more likely to have
      hyperhomocysteinemia than those without folate deficiency. The vitamin B (12)
      level associated with hyperhomocysteinemia was lower in pregnant subjects than in
      nonpregnant subjects in this study, indicating that pregnant women require
      vitamin B (12) supplementation.

PMID- 15580544
TI  - Interleukin-6 and tumor necrosis factor alpha as predictors of success after
      emergent cerclage.
AB  - Serum levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)
      were measured in patients requiring an emergent cerclage to determine if they are
      predictive of successful pregnancy outcome. Women with a clinical diagnosis of
      cervical incompetence requiring an emergent cerclage between 15 and 24 weeks
      gestation were enrolled. Asymptomatic women of the same gestational age range
      were recruited as controls. IL-6 and TNF-alpha levels were measured by enzyme
      linked immunosorbent assay. Twenty-one women underwent emergent cerclage and
      participated in the study, 15 (71%) of whom delivered after 28 weeks. Twenty-one
      women served as controls. IL-6 levels were increased in women with cervical
      incompetence compared with control subjects, but there were no differences
      between cerclage success and failure groups. TNF-alpha was not increased in women
      with cervical incompetence and did not predict success of emergent cerclage. IL-6
      levels were increased in women with cervical incompetence who required an
      emergent cerclage.

PMID- 15580545
TI  - Periventricular echogenicity is related to delayed neurodevelopment of preterm
      infants.
AB  - Periventricular leukomalacia (PVL) is one of the most commonly seen
      neuropathologic lesions and is related to many neurodevelopmental handicaps in
      premature infants. Periventricular echogenicities (PVE) are considered to be at
      the milder end of the spectrum of PVL, and thus might affect the neurodevelopment
      of the preterm infants as well. In this retrospective cohort study medical
      records of 257 preterm infants who were discharged from our neonatal intensive
      care unit (NICU) during October 1996 to August 2000 were reviewed. A total of 114
      records of preterm infants fulfilling our criteria were included in the survey.
      On the basis of the craniosonographic findings and birth history, the candidates
      were divided into three subgroups: group 1 (control) included infants with normal
      craniosonographic image during the neonatal period; group 2 included infants with
      PVEs for < 2 weeks during the neonatal period; group 3 included infants with
      PVEs> or = 2 weeks during the neonatal period. Neurodevelopmental assessment
      using the Bayley Scale of Infant Development II at 6, 12, and 18 months of
      corrected age of each group was compared. There were no significant differences
      among the three groups in gestational age, birth weight, and gender prevalence.
      Infants in group 3 had lower Mental Developmental Index and Psychomotor
      Developmental Index scores as compared with those in groups 1 and 2 at 6 ( p<
      0.01), 12 ( p < 0.001), and 18 ( p < 0.01) months of corrected age, respectively.
      In conclusion, infants with PVEs that persisted for at least a 2-week period have
      significantly higher risk of delayed developmental outcomes as compared with
      infants with normal craniosonography or infants with PVEs that persisted for less
      than 2 weeks. It might be prudent to arrange therapeutic intervention for
      rehabilitation to these high-risk infants as early as possible to reduce the
      intensity of possible handicap in the future.

PMID- 15580546
TI  - Streptococcus pneumoniae: an old bug with significant maternal-newborn
      implications.
AB  - Streptococcus pneumoniae is an uncommon organism identified in neonatal
      bacteremia, but when it occurs, it has serious implications for both the infant
      and the mother. Despite the similarities in the manifestations between group B
      streptococcus and S. pneumoniae sepsis, the latter appears to be more virulent
      and of marked severity, resulting in significant neonatal mortality. In the
      absence of a routine maternal screening protocol for S. pneumoniae colonization,
      aggressive newborn management constitutes the mainstay of treatment.

PMID- 15580547
TI  - Identification of a 3.0-kb major recombination hotspot in patients with Sotos
      syndrome who carry a common 1.9-Mb microdeletion.
AB  - Sotos syndrome (SoS) is a congenital dysmorphic disorder characterized by
      overgrowth in childhood, distinctive craniofacial features, and mental
      retardation. Haploinsufficiency of the NSD1 gene owing to either intragenic
      mutations or microdeletions is known to be the major cause of SoS. The common
      approximately 2.2-Mb microdeletion encompasses the whole NSD1 gene and
      neighboring genes and is flanked by low-copy repeats (LCRs). Here, we report the
      identification of a 3.0-kb major recombination hotspot within these LCRs, in
      which we mapped deletion breakpoints in 78.7% (37/47) of patients with SoS who
      carry the common microdeletion. The deletion size was subsequently refined to 1.9
      Mb. Sequencing of breakpoint fragments from all 37 patients revealed junctions
      between a segment of the proximal LCR (PLCR-B) and the corresponding region of
      the distal LCR (DLCR-2B). PLCR-B and DLCR-2B are the only directly oriented
      regions, whereas the remaining regions of the PLCR and DLCR are in inverted
      orientation. The PLCR, with a size of 394.0 kb, and the DLCR, with a size of of
      429.8 kb, showed high overall homology (approximately 98.5%), with an increased
      sequence similarity (approximately 99.4%) within the 3.0-kb breakpoint cluster.
      Several recombination-associated motifs were identified in the hotspot and/or its
      vicinity. Interestingly, a 10-fold average increase of a translin motif, as
      compared with the normal distribution within the LCRs, was recognized.
      Furthermore, a heterozygous inversion of the interval between the LCRs was
      detected in all fathers of the children carrying a deletion in the paternally
      derived chromosome. The functional significance of these findings remains to be
      elucidated. Segmental duplications of the primate genome play a major role in
      chromosomal evolution. Evolutionary study showed that the duplication of the SoS
      LCRs occurred 23.3-47.6 million years ago, before the divergence of Old World
      monkeys.

PMID- 15580548
TI  - The R620W polymorphism of the protein tyrosine phosphatase PTPN22 is not
      associated with multiple sclerosis.

PMID- 15580549
TI  - Corrections to the parameterization of constraints on allele sharing in sibling
      pairs alter covariate-parameter estimates but not sharing-probability estimates
      or power of tests for linkage.

PMID- 15580550
TI  - Challenging conventional wisdom: the etiologic role of dopamine oxidative stress
      in Parkinson's disease.
AB  - Oxidative stress is well documented in Parkinson's disease (PD) and has been
      attributed to dopamine oxidative metabolism. However, evidence of oxidative
      stress is found in a variety of neurodegenerative disorders, suggesting that more
      general factors are responsible or that cytodestructive processes secondarily
      generate oxyradical products. Increasing evidence points away from dopamine
      metabolism as an important contributor to PD neurodegeneration. Predictions from
      the dopamine oxidative stress hypothesis of PD reveal multiple inconsistencies.
      Although the clinical and therapeutic importance of the nigrostriatal
      dopaminergic system is undeniable, PD neuropathology is much more widespread.

PMID- 15580551
TI  - HAEdb: a novel interactive, locus-specific mutation database for the C1 inhibitor
      gene.
AB  - Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder
      characterized by episodic local subcutaneous and submucosal edema and is caused
      by the deficiency of the activated C1 esterase inhibitor protein (C1-INH or
      C1INH; approved gene symbol SERPING1). Published C1-INH mutations are represented
      in large universal databases (e.g., OMIM, HGMD), but these databases update their
      data rather infrequently, they are not interactive, and they do not allow
      searches according to different criteria. The HAEdb, a C1-INH gene mutation
      database (http://hae.biomembrane.hu) was created to contribute to the following
      expectations: 1) help the comprehensive collection of information on genetic
      alterations of the C1-INH gene; 2) create a database in which data can be
      searched and compared according to several flexible criteria; and 3) provide
      additional help in new mutation identification. The website uses MySQL, an open
      source, multithreaded, relational database management system. The user-friendly
      graphical interface was written in the PHP web programming language. The website
      consists of two main parts, the freely browsable search function, and the
      password-protected data deposition function. Mutations of the C1-INH gene are
      divided in two parts: gross mutations involving DNA fragments >1 kb, and micro
      mutations encompassing all non-gross mutations. Several attributes (e.g.,
      affected exon, molecular consequence, family history) are collected for each
      mutation in a standardized form. This database may facilitate future
      comprehensive analyses of C1-INH mutations and also provide regular help for
      molecular diagnostic testing of HAE patients in different centers.

PMID- 15580552
TI  - Falls and injuries resulting from falls among patients with Parkinson's disease
      and other parkinsonian syndromes.
AB  - We sought to ascertain frequency, type, risk factors of falling, and resulting
      injuries among parkinsonian patients. A survey was mailed to all patients treated
      at our center between 1/1/2000 and 4/30/2002 (N = 1,417). Information was
      collected on falls within the past 2 years, related injuries, and use of health
      care services. A total of 1,131 responses (response rate, 79.8%) were received.
      After the exclusion of nonparkinsonian disorders, statistics for the remaining
      group (n = 1,092) and predictive statistics for those diagnosed before 1/1/2000
      (n = 1,013) were calculated. Outcomes included falls, fractures, injuries,
      surgery, and related use of health care services. Explanatory variables included
      sex, age, age at diagnosis, disease duration, atypical parkinsonism, and
      dementia. Most patients (55.9%) were men; 12.2% had atypical parkinsonism; 12.5%
      had dementia; median age was 74.7 years; median disease duration was 7 years;
      55.9% had at least one fall in the past 2 years; 65.0% of them sustained an
      injury; 33.0% sustained a fracture; 75.5% of injuries required health care
      services; 40.6% of fractures required surgery. Older age, atypical parkinsonism,
      longer disease duration, and dementia were risk factors for falling; female sex
      and older age were predictors of fractures. Need for health care services after
      an injury was higher among older patients. Further prospective studies will be
      necessary to elucidate the specific prognostic outcomes of injuries due to falls
      among parkinsonian patients, and the impact of these injuries on disease
      progression and quality of life.

PMID- 15580553
TI  - Reassessment of the TP53 mutation database in human disease by data mining with a
      library of TP53 missense mutations.
AB  - TP53 alteration is the most frequent genetic alteration found in human cancers.
      To date, more than 15,000 tumors with TP53 mutations have been published, leading
      to the description of more than 1,500 different TP53 mutants
      (http://p53.curie.fr). The frequency of these mutants is highly heterogeneous,
      with 11 hotspot mutants found more than 100 times, whereas 306 mutants have been
      reported only once. So far, little is known concerning the biological
      significance of these rare mutants, as the majority of biological studies have
      focused on classic hotspot mutants. In order to gain a deeper knowledge about the
      significance of all of these mutants, we have cross-checked each mutant of the
      TP53 mutation database for its activity, derived from a library of 2,314 TP53
      mutants representing all possible amino acid substitutions caused by a point
      mutation. The transactivation activity of all of these mutant was analyzed with
      respect to eight transcription promoters [Kato S, et al., Proc Natl Acad Sci USA
      (2003)100:8424-8429]. Although the most frequent TP53 mutants sustain a clear
      loss of transactivation activity, more than 50% of the rare TP53 mutants display
      significant activity. Analysis in specific types of cancer or in normal skin
      patches demonstrates a similar distribution of TP53 loss of activity, with the
      exception of melanoma, in which the majority of TP53 mutants display significant
      activity. Our data indicate that TP53 mutants represent a highly heterogeneous
      population with a large diversity in terms of loss of transactivation activity
      that could account for the heterogeneous tumor phenotypes and the difficulty of
      clinical studies.

PMID- 15580554
TI  - Regulation of iro3 expression in the zebrafish spinal cord.
AB  - Specification of spinal cord neurons is regulated by several different
      transcription factors. In this study, we analyze expression and regulation of the
      transcription factor iro3 in zebrafish spinal cord. In addition to its broad
      expression in the progenitor domain of intermediate spinal cord, iro3 is also
      expressed in postmitotic ventral neurons, starting at early somitogenesis stages.
      Initially, this expression is only in two primary motoneurons, CaP and VaP, but
      by 24 hr postfertilization, iro3 is expressed by all classes of zebrafish spinal
      motoneurons as well as by a ventral interneuron called VeLD. iro3 expression in
      the progenitor domain of intermediate spinal cord is regulated independently from
      its expression in ventral neurons. Hedgehog (Hh) signaling is unnecessary for
      iro3 expression in intermediate spinal cord, but it is required to repress iro3
      expression in the progenitor domain of ventral spinal cord. We also show that the
      basic helix-loop-helix transcription factor Olig2 is required for repression of
      iro3 expression in the progenitor domain of ventral spinal cord. We discuss our
      findings in the context of previous studies, suggesting that iro3 represses
      formation of motoneurons and promotes formation of interneurons.

PMID- 15580555
TI  - Turtle-chicken chimera: an experimental approach to understanding evolutionary
      innovation in the turtle.
AB  - Turtles have a body plan unique among vertebrates in that their ribs have shifted
      topographically to a superficial layer of the body and the trunk muscles are
      greatly reduced. Identifying the developmental factors that cause this pattern
      would further our understanding of the evolutionary origin of the turtles. As the
      first step in addressing this question, we replaced newly developed epithelial
      somites of the chicken at the thoracic level with those of the Chinese soft
      shelled turtle Pelodiscus sinensis (P. sinensis somites into a chicken host) and
      observed the developmental patterning of the grafted somites in the chimera. The
      P. sinensis somites differentiated normally in the chicken embryonic environment
      into sclerotomes and dermomyotomes, and the myotomes differentiated further into
      the epaxial and hypaxial muscles with histological morphology similar to that of
      normal P. sinensis embryos and not to that of the chicken. Epaxial dermis also
      arose from the graft. Skeletal components, however, did not differentiate from
      the P. sinensis sclerotome, except for small fragments of cartilage associated
      with the host centrum and neural arches. We conclude that chicken and P. sinensis
      share the developmental programs necessary for the early differentiation of
      somites and that turtle-specific traits in muscle patterning arise mainly through
      a cell-autonomous developmental process in the somites per se. However, the
      mechanism for turtle-specific cartilage patterning, including that of the ribs,
      is not supported by the chicken embryonic environment.

PMID- 15580556
TI  - Pallidal deep brain stimulation influences both reflexive and voluntary saccades
      in Huntington's disease.
AB  - Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is being
      evaluated as a potential new therapy for patients with Huntington's disease (HD).
      In addition to skeletal movement disorders, HD patients have difficulty
      initiating voluntary saccades and have difficulty in suppressing rapid saccades
      toward newly appearing stimuli. We measured several saccade parameters in an HD
      patient who had marked improvement of clinical symptoms with bilateral GPi DBS to
      determine whether oculomotor performance improved in parallel with clinical
      scores. Oculomotor performance was assessed using three testing paradigms: pro
      saccades, anti-saccades, and memory-guided saccades. The data from the HD patient
      was also compared to that of two healthy controls. Pallidal DBS decreased pro
      saccade latency, total movement time, and the number of correctly executed
      trials, as well as increasing saccade gain. Memory-saccade performance was
      negatively affected with stimulation: saccade gain decreased, latency increased,
      and the patient's ability to suppress unwanted saccades decreased with
      stimulation. Our data demonstrate a task-specific improvement of oculomotor
      deficits in this HD patient with pallidal DBS, supporting a role of GPi in
      oculomotor control.

PMID- 15580557
TI  - Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors.
AB  - HM74 (GPR109B) and the highly homologous gene, HM74A (GPR109A) code for Gi-G
      protein-coupled orphan receptors that recently have been discovered to be
      involved in the metabolic effects of niacin. The B vitamin niacin is an important
      agent used in the treatment of dyslipidemias, but its use is limited by side
      effects. The novel role of the adjacent HM74 and HM74A genes in the metabolism of
      niacin may provide new targets for drug development. Human genetic variations in
      HM74 and HM74A have been reported but have not been studied in detail. These
      variations may play a role in the response to agents targeting receptors coded by
      these genes. Here we show that many of the nonsynonymous SNPs listed in public
      databases for HM74 and HM74A are artifacts resulting from extensive homology
      between these two genes. This may be representative of a neglected phenomenon in
      reporting sequences of highly homologous genes. We provide primer sequences that
      permit selective amplification of the complete coding regions of HM74 and HM74A.
      Using these primers, we show that subsequent sequencing of HM74 and HM74A reveals
      a novel and unique variation in the HM74A gene. Haplotype analysis suggests four
      SNPs can define the five major haplotypes that lie within a single haplotype
      block encompassing these two genes.

PMID- 15580558
TI  - KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.
AB  - Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by
      severe hyperglycemia constantly requiring insulin treatment from its onset.
      Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic
      etiology is unknown in most PNDM patients. Recently, heterozygous activating
      mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP
      dependent potassium (K(ATP)) channel of the pancreatic beta-cell, were found in
      patients with PNDM. Closure of the K(ATP) channel exerts a pivotal role in
      insulin secretion by modifying the resting membrane potential that leads to
      insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM
      (onset within 3 months from birth) and in six patients with non-autoimmune,
      insulin-requiring diabetes diagnosed during the first year of life. Five
      different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A
      (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight
      patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and
      Lys170 residues are novel. Four patients also presented with motor and/or
      developmental delay as previously reported. We conclude that KCNJ11 mutations are
      a common cause of PNDM either in isolation or associated with developmental
      delay. Permanent diabetes of non autoimmune origin can present up to 6 months
      from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we
      suggest that the acronym PNDM be replaced with the more comprehensive permanent
      diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK
      PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset,
      autoimmune type 1 diabetes.

PMID- 15580559
TI  - The molecular basis of classic Ehlers-Danlos syndrome: a comprehensive study of
      biochemical and molecular findings in 48 unrelated patients.
AB  - Classic Ehlers-Danlos syndrome (EDS) is characterized by fragile and
      hyperextensible skin, atrophic scarring, and joint hypermobility. Mutations in
      the COL5A1 and the COL5A2 gene encoding the alpha1(V) and the alpha2(V) chains,
      respectively, of type V collagen have been shown to cause the disorder, but it is
      unknown what proportion of classic EDS patients carries a mutation in these
      genes. We studied fibroblast cultures from 48 patients with classic EDS by SDS
      PAGE for the presence of type V collagen defects. An abnormal collagen pattern
      was detected in only 2 out of 48 cell lines, making this a poor method for
      routine diagnostic evaluation. A total of 42 out of 48 (88%) patients were
      heterozygous for an expressed polymorphic variant in COL5A1. cDNA from 18 (43%)
      of them expressed only one COL5A1 allele. In 37 patients, the COL5A1/A2 genes
      were then analyzed by SSCP and conformation sensitive gel electrophoresis (CSGE).
      A total of 26 patients that were mutation-negative after SSCP/CSGE screening were
      reanalyzed by dHPLC. In addition, 11 other patients were analyzed by dHPLC only.
      In total, 17 mutations leading to a premature stop codon and five structural
      mutations were identified in the COL5A1 and the COL5A2 genes. In three patients
      with a positive COL5A1 null-allele test, no causal mutation was found. Overall,
      in 25 out of 48 patients (52%) with classic EDS, an abnormality in type V
      collagen was confirmed. Variability in severity of the phenotype was observed,
      but no significant genotype-phenotype correlations emerged. The relatively low
      mutation detection rate suggests that other genes are involved in classic EDS. We
      excluded the COL1A1, COL1A2, and DCN gene as major candidate genes for classic
      EDS, since no causal mutation in these genes was found in a number of patients
      who tested negative for COL5A1 and COL5A2.

PMID- 15580560
TI  - The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I
      (LGMD2I) may have occurred only once and is present in Hutterites and other
      populations.
AB  - Limb girdle muscular dystrophy (LGMD) is common in the Hutterite population of
      North America. We previously identified a mutation in the TRIM32 gene in
      chromosome region 9q32, causing LGMD2H in approximately two-thirds of the 60
      Hutterite LGMD patients studied to date. A genomewide scan was undertaken in five
      families who did not show linkage to the LGMD2H locus on chromosome 9. A second
      LGMD locus, LGMD2I, was identified in chromosome region 19q13.3, and the
      causative mutation was identified as c.826C>A (L276I), a missense mutation in the
      FKRP gene. A comparison of the clinical characteristics of the two LGMD patient
      groups in this population reveals some differences. LGMD2I patients generally
      have an earlier age at diagnosis, a more severe course, and higher serum creatine
      kinase (CK) levels. In addition, some of these patients show calf hypertrophy,
      cardiac symptoms, and severe reactions to general anesthesia. None of these
      features are present among LGMD2H patients. A single common haplotype surrounding
      the FKRP gene was identified in the Hutterite LGMD2I patients. An identical core
      haplotype was also identified in 19 other non-Hutterite LGMD2I patients from
      Europe, Canada, and Brazil. The occurrence of this mutation on a common core
      haplotype suggests that L276I is a founder mutation that is dispersed among
      populations of European origin.

PMID- 15580561
TI  - Breakpoint analysis of the pericentric inversion distinguishing human chromosome
      4 from the homologous chromosome in the chimpanzee (Pan troglodytes).
AB  - The study of breakpoints that occurred during primate evolution promises to yield
      valuable insights into the mechanisms underlying chromosome rearrangements in
      both evolution and pathology. Karyotypic differences between humans and
      chimpanzees include nine pericentric inversions, which may have potentiated the
      parapatric speciation of hominids and chimpanzees 5-6 million years ago. Detailed
      analysis of the respective chromosomal breakpoints is a prerequisite for any
      assessment of the genetic consequences of these inversions. The breakpoints of
      the inversion that distinguishes human chromosome 4 (HSA4) from its chimpanzee
      counterpart were identified by fluorescence in situ hybridization (FISH) and
      comparative sequence analysis. These breakpoints, at HSA4p14 and 4q21.3, do not
      disrupt the protein coding region of a gene, although they occur in regions with
      an abundance of LINE and LTR-elements. At 30 kb proximal to the breakpoint in
      4q21.3, we identified an as yet unannotated gene, C4orf12, that lacks an
      homologous counterpart in rodents and is expressed at a 33-fold higher level in
      human fibroblasts as compared to chimpanzee. Seven out of 11 genes that mapped to
      the breakpoint regions have been previously analyzed using oligonucleotide
      microarrays. One of these genes, WDFY3, exhibits a three-fold difference in
      expression between human and chimpanzee. To investigate whether the genomic
      architecture might have facilitated the inversion, comparative sequence analysis
      was used to identify an approximately 5-kb inverted repeat in the breakpoint
      regions. This inverted repeat is inexact and comprises six subrepeats with 78 to
      98% complementarity. (TA)-rich repeats were also noted at the breakpoints. These
      findings imply that genomic architecture, and specifically high-copy repetitive
      elements, may have made a significant contribution to hominoid karyotype
      evolution, predisposing specific genomic regions to rearrangements.

PMID- 15580562
TI  - Harmaline-induced tremor as a potential preclinical screening method for
      essential tremor medications.
AB  - No preclinical method to evaluate potential new medications for essential tremor
      (ET) is available currently. Although harmaline tremor is a well known animal
      model of ET, it has not found utility as a preclinical drug screen and has not
      been validated with anti-ET medications. We measured harmaline tremor in rats (10
      mg/kg s.c.) and mice (20 mg/kg s.c.) with a load sensor under the cage floor and
      performed spectral analysis on 20-minute epochs. The motion power over the tremor
      frequency bandwidth (8-12 Hz in rats; 10-16 Hz in mice) was divided by the motion
      power over the full motion frequency range (0-15 Hz in rats; 0-34 Hz in mice).
      The use of these measures greatly reduced data variability, permitting
      experiments with small sample sizes. Three drugs that suppress ET (propranolol,
      ethanol, and octanol) all significantly suppressed harmaline-induced tremor. We
      propose that, with this methodology, harmaline-induced tremor may be useful as a
      preclinical method to identify potential medications for ET.

PMID- 15580563
TI  - DNMT3B mutations and DNA methylation defect define two types of ICF syndrome.
AB  - ICF syndrome is a rare autosomal recessive disease characterized by variable
      immunodeficiency, centromeric instability, and facial abnormalities. Mutations in
      the catalytic domain of DNMT3B, a gene encoding a de novo DNA methyltransferase,
      have been recognized in a subset of patients. ICF syndrome is a genetic disease
      directly related to a genomic methylation defect that mainly affects classical
      satellites 2 and 3, both components of constitutive heterochromatin. The variable
      incidence of DNMT3B mutations and the differential methylation defect of alpha
      satellites allow the identification of two types of patients, both showing an
      undermethylation of classical satellite DNA. This classification illustrates the
      specificity of the methylation process and raises questions about the genetic
      heterogeneity of the ICF syndrome.

PMID- 15580564
TI  - Molecular and functional analysis of intragenic SMN1 mutations in patients with
      spinal muscular atrophy.
AB  - The autosomal recessive spinal muscular atrophy (SMA), a neuromuscular disease
      and frequent cause of early death in childhood, is caused in 96% of patients by
      homozygous absence of the survival motor neuron gene (SMN1). The severity of the
      disease is mainly determined by the copy number of SMN2, a copy gene which
      predominantly produces exon 7-skipped transcripts and only low amount of full
      length transcripts that encode for a protein identical to SMN1. Only about 4% of
      SMA patients bear one SMN1 copy with an intragenic mutation. A comprehensive
      molecular genetic analysis of 34 SMA patients who carry one SMN1 gene is
      presented, including 18 that were previously published. Haplotype analysis with
      the microsatellite markers Ag1-CA and C212 in these SMA families turned out to be
      a reliable accessory method in predicting known SMN1 mutations in SMA patients
      carrying one SMN1 copy. Five novel missense mutations were identified that are
      localized in: exon 2a c.88G>A (p.D30N) and c.131A>T (p.D44V); exon 3 c.283G>C
      (p.G95R) and c.332C>G (p.A111G); and exon 6 c.784A>G (p.S262G), respectively. The
      survival motor neuron (SMN) protein has been shown to be a component of a large
      complex (termed the SMN complex) that promotes the formation of spliceosomal U
      small nuclear ribonucleoproteins (snRNPs). Within this complex, SMN forms
      oligomers and directly interacts via its N-terminus with SMN-interacting protein
      1 (SIP1) and via its central Tudor domain with spliceosomal (Sm) proteins. We
      performed in vitro interaction studies to test whether SMA-causing missense
      mutations identified in this study interfere with the reported interactions of
      SMN. Our results show that mutations p.G95R and p.A111G reduce SMN binding to Sm
      proteins, further confirming the previous finding that the Tudor domain is the
      essential binding site of SMN to Sm-proteins. However, all mutations, including
      those in exon 2a, a region shown to be important for the binding of SMN to SIP1,
      do not disturb the interaction of SMN to SIP1.

PMID- 15580565
TI  - A T3 allele in the CFTR gene exacerbates exon 9 skipping in vas deferens and
      epididymal cell lines and is associated with Congenital Bilateral Absence of Vas
      Deferens (CBAVD).
AB  - The different alleles at the (TG)m(T)n polymorphic loci at the 3' end of the
      human CFTR intron 8 determine the efficiency by which exon 9 is spliced. We
      identified a novel TG12T3 allele in a congenital bilateral absence of vas
      deferens (CBAVD) patient who carries a [TG11T7; p.Phe508Cys; p.Met470Val]
      haplotype on the other chromosome. To better understand the complex regulation of
      exon 9 splicing, we analyzed the levels of correctly spliced CFTR transcripts in
      six CFTR-expressing epithelial cell lines derived from lung, colon, testis, vas
      deferens, and epididymis transiently transfected with four CFTR minigenes
      (pTG11T7, pTG12T7, pTG12T5, and pTG12T3). In this work, we show that a decrease
      in the Ts at the polymorphic locus in a TG12 background determines a cell-type
      dependent reduction in exon 9+ transcripts that is not related to the basal
      splicing efficiency in the cell line. These data emphasize the role of the T5
      allele in CBAVD and identify the T3 allele as a severe cystic fibrosis (CF)
      disease-causing mutation. Finally, UV cross-linking experiments demonstrated that
      tissue-specific trans-acting splicing factors do not contribute to the different
      patterns of exon 9 splicing found between the cell lines. However, we observed
      that lower numbers of Ts can alter the binding of TDP-43 (TDP43 or TARDBP) to its
      specific target ug12 in a tissue-specific manner. Our results support the idea
      that the ratio of general splicing factors plays a role in the tissue variability
      of exon 9 alternative splicing.

PMID- 15580566
TI  - Molecular and muscle pathology in a series of caveolinopathy patients.
AB  - Mutations in the caveolin-3 gene (CAV3) cause limb girdle muscular dystrophy
      (LGMD) type 1C (LGMD1C) and other muscle phenotypes. We screened 663 patients
      with various phenotypes of unknown etiology, for caveolin-3 protein deficiency,
      and we identified eight unreported caveolin-deficient patients (from seven
      families) in whom four CAV3 mutations had been detected (two are unreported).
      Following our wide screening, we estimated that caveolinopathies are 1% of both
      unclassified LGMD and other phenotypes, and demonstrated that caveolin-3 protein
      deficiency is a highly sensitive and specific marker of primary caveolinopathy.
      This is the largest series of caveolinopathy families in whom the effect of gene
      mutations has been analyzed for protein level and phenotype. We showed that the
      same mutation could lead to heterogeneous clinical phenotypes and muscle
      histopathological changes. To study the role of the Golgi complex in the
      pathological pathway of misfolded caveolin-3 oligomers, we performed a
      histopathological study on muscle biopsies from caveolinopathy patients. We
      documented normal caveolin-3 immunolabeling at the plasmalemma in some
      regenerating fibers showing a proliferation of the Golgi complex. It is likely
      that caveolin-3 overexpression occurring in regenerating fibers (compared with
      caveolin-deficient adult fibers) may lead to an accumulation of misfolded
      oligomers in the Golgi and to its consequent proliferation.

PMID- 15580567
TI  - Praying-induced oromandibular dystonia.
AB  - We report on an unusual presentation of a task-specific focal oromandibular
      dystonia in a 47-year-old man of Turkish descent. His speech was affected
      exclusively while reciting Islamic prayers in Arabic language, which he otherwise
      did not speak.

PMID- 15580568
TI  - Abnormal development of the intercostal muscles and the rib cage in Myf5-/-
      embryos leads to pulmonary hypoplasia.
AB  - The aim of our study was to investigate the importance of pulmonary distension
      and fetal breathing-like movements executed by the contractile activity of the
      intercostal respiratory muscles for proper lung growth and maturation. Lung
      development in Myf5-/- embryos, lacking the rib cage and functional intercostal
      musculature, was compared with wild-type controls at embryonic days 14.5, 16.5,
      and 18.5. Our data revealed that Myf5-/- embryos suffered from pulmonary
      hypoplasia in part due to the decreased number of proliferating lung cells and in
      part due to the increased number of terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) -positive cells. In addition, the
      proximal-to-distal expression gradient of thyroid transcription factor-1 observed
      in wild-type embryos was not maintained in Myf5-/- embryos. The number of lung
      cells expressing platelet-derived growth factor-BB, its receptor and insulin
      growth factor-I was significantly decreased in the hypoplastic lung. By contrast,
      no difference in the expression pattern of surfactant associated proteins or
      Clara cells marker was detected between wild-type and Myf5-/- embryos.
      Collectively, our data suggest that the mechanochemical signal transduction
      pathway used in vitro is also effective in vivo influencing lung growth but not
      lung cell maturation and resulting in lung hypoplasia. These data affirm the role
      of fetal breathing-like movements in lung organogenesis.

PMID- 15580569
TI  - Phenotology of disease-linked proteins.
AB  - Are there analogous sequence positions in families of related proteins where
      disease-linked mutations occur with unusually high frequency? We attempt to
      answer this question by examining sequence alignments for G-protein coupled
      receptors (GPCRs) and voltage-gated potassium channels that have a significant
      number of missense mutations linked to some form of human disease. When the
      disease-linked mutations are mapped onto the sequences for each family, there are
      a large number of aligned sites at which disease-linked mutations occur in more
      than one protein. The statistical significance of the aligned sites is judged by
      analysis of artificially-generated random datasets. There are a modest number of
      aligned sites that are statistically significant-we refer to these as
      "phenotologous" sequence positions. Phenotologous sites represent aligned
      positions at which mutations linked to disease phenotypes occur with high
      frequency within a family of proteins. The most interesting of these sites are
      those which are not conserved-such sites are apparently critical in defining
      structural or functional differences between related proteins. Phenotology may be
      used to make experimentally testable predictions regarding medical genetics, the
      molecular basis of disease, and protein structure-function relationships.

PMID- 15580570
TI  - Peripheral blood fibrocytes contribute to the formation of the avian spleen.
AB  - Chick-quail chimeric studies were made to determine the origin of the cells of
      splenic ellipsoid. The ellipsoid is formed by supporting and phagocytic cells,
      which are embedded in a well-organized extracellular matrix. Splenic and bursal
      anlage of 6- to 6.5-day-old quail embryos were transplanted into the coelomic
      cavity of 3-day-old chick embryos and further incubated for 17 days. CD45+
      chicken hemopoietic cells colonized both organs. They formed the cells of the
      ellipsoid and the periellipsoidal white pulp of the transplanted quail spleen.
      Chicken-specific collagen III was produced only in the donor quail spleen, but
      not in the bursa of Fabricius. The CD45+/collagen I+/collagen III+ cells are
      probably identical with the mammalian peripheral blood fibrocytes and contribute
      to the formation of supporting cells, whereas the CD45+/74.2+ ellipsoid
      associated macrophages are of monocytic origin. We provide, for the first time,
      experimental evidence that peripheral blood fibrocytes exist in the avian
      species; they are present in the circulation of the chicken embryo and contribute
      to the organogenesis of the spleen.

PMID- 15580571
TI  - Clearance of apoptotic cells is not impaired in mouse embryos deficient in class
      A scavenger receptor types I and II (CD204).
AB  - Elimination of apoptotic cells is an important mechanism to maintain proper
      embryonal morphogenesis. The class A scavenger receptor type I, II (CD204), one
      of the major receptors expressed on macrophages, is a receptor actively involved
      in recognition and ingestion of apoptotic cells. To clarify the role of CD204 in
      embryonic morphogenesis, we performed immunohistochemical and immunoelectron
      microscopic studies using CD204-deficient mouse embryos. In control mice, almost
      all macrophages expressed CD204 from embryonic day 9.5 (E9.5). Phagocytes
      engulfing dead cells in the E13.5 interdigit region showed strong expression of
      CD204, indicating that CD204 was actively involved in apoptotic cell clearance.
      However, CD204 is not essential for the embryonic clearance of apoptotic cells,
      because CD204-deficient embryos developed normally without any retardation in
      footplate remodeling. Up-regulation of CD36 in CD204-deficient fetal macrophages
      suggested that CD36 substitutes for CD204 function. We also found that
      mesenchymal cells frequently engulfed apoptotic cells especially in early
      embryonal stages. These data suggest that CD204 is partially but not essentially
      involved in apoptotic cell clearance in embryogenesis. During early embryonal
      development, mesenchymal cells, rather than macrophages, play a major role in
      apoptotic cell clearance.

PMID- 15580572
TI  - Protein kinase A regulates cell cycle progression of mouse fertilized eggs by
      means of MPF.
AB  - Cell cycle of one-cell stage mouse fertilized eggs was accompanied by fluctuation
      in the concentration of adenosine 3'5'-monophosphate (cAMP) and in the activity
      of free catalytic subunit of cAMP-dependent protein kinase (PKA). The
      concentration of cAMP and the activity of free catalytic subunit of PKA decreased
      at the onset of mitosis and increased at the transition between mitosis and G1
      phase. Stimulation of PKA by microinjection of cAMP into one-cell stage mouse
      embryos at G2 phase induced interphase arrest and prevented the activation of M
      phase promoting factor (MPF). Upon blockage of the activation of PKA by
      microinjecting a thermostable PKA inhibitor (PKI) into one-cell stage mouse
      embryos at G2 phase, the increase in the MPF activity occurred 30 min earlier
      than in control group. When a high dose of PKI was microinjected, a transition
      into interphase was prevented, and the activity of MPF remained high. Western
      blot analysis showed that Cdc2 remained phosphorylated in cAMP microinjected
      embryos by the time when control embryos were at metaphase and showed
      dephosphorylated Cdc2; conversely, Cdc2 dephosphorylation was accelerated in PKI
      microinjected embryos. At the same time, Cdc2 was phosphorylated at Tyr15 at G2
      phase and even at M phase when cAMP was microinjected but was dephosphorylated
      when PKI was microinjected. PKI microinjection also prevented cyclin B
      degradation and sustained MPF activity, thus delaying the transition from
      metaphase to anaphase. Our results show that PKA, by inhibiting MPF, regulates
      cell cycle progression of fertilized eggs.

PMID- 15580573
TI  - Thematic similarity and clinical outcome in obsessive-compulsive disorder group
      treatment.
AB  - Despite the existence of efficacious cognitive-behavioral group treatments for
      obsessive-compulsive disorder (OCD), no data has been presented regarding the
      potential impact of symptom or thematic similarity among group members. The
      purpose of this study was to evaluate the effect of thematic similarity among
      group members on outcome after cognitive-behavioral (CBT) or exposure/response
      prevention (ERP) treatment for OCD. Results consistently demonstrated across a
      range of measures no impact of thematic similarity, nor any interaction of
      similarity by treatment type (ERP versus CBT), on treatment outcome. These data
      suggest that OCD treatment groups can be formed based on consecutive client
      intake without negatively impacting efficacy.

PMID- 15580574
TI  - Quality of life and post trauma symptomatology in motor vehicle accident
      survivors: the mediating effects of depression and anxiety.
AB  - We examined the respective contributions of depression, anxiety, and post-trauma
      symptoms, as these factors reduce quality of life (QOL) in 111 individuals who
      had experienced a serious motor vehicle accident. Correlations and structural
      equation modeling were used to evaluate whether the severity of posttraumatic
      stress disorder symptoms influences QOL directly, and whether depression and
      anxiety mediated this relationship. Results indicated that post trauma
      symptomatology has a negative effect on QOL, which is mediated by depression and
      anxiety.

PMID- 15580575
TI  - Causes of proteolytic degradation of secreted recombinant proteins produced in
      methylotrophic yeast Pichia pastoris: case study with recombinant ovine
      interferon-tau.
AB  - It was observed that during fermentative production of recombinant ovine
      interferon-tau (r-oIFN-tau) in Pichia pastoris, a secreted recombinant protein,
      the protein was degraded increasingly after 48 h of induction and the rate of
      degradation increased towards the end of fermentation at 72 h, when the
      fermentation was stopped. Proteases, whose primary source was the vacuoles, was
      found in increasing levels in the cytoplasm and in the fermentation broth after
      48 h of induction and reached maximal values when the batch was completed at 72
      h. Protease levels at various cell fractions as well as in the culture
      supernatant were lower when glycerol was used as the carbon source instead of
      methanol. It can be concluded that methanol metabolism along with cell lysis
      towards the end of fermentation contributes to increased proteolytic activity and
      eventual degradation of recombinant protein.

PMID- 15580576
TI  - Broad-spectrum protein biosensors for class-specific detection of antibiotics.
AB  - The dramatically increasing prevalence of multi-drug-resistant human pathogenic
      bacteria and related mortality requires two key actions: (i) decisive initiatives
      for the detection of novel antibiotics and (ii) a global ban for use of
      antibiotics as growth promotants in stock farming. Both key actions entail
      technology for precise, high-sensitive detection of antibiotic substances either
      to detect and validate novel anti-infective structures or to enforce the non-use
      of clinically relevant antibiotics. We have engineered prokaryotic antibiotic
      response regulators into a molecular biosensor configuration able to detect
      tetracycline, streptogramin, and macrolide antibiotics in spiked liquids
      including milk and serum at ng/mL concentrations and up to 2 orders of magnitude
      below current Swiss and EC threshold values. This broad-spectrum, class-specific,
      biosensor-based assay has been optimized for use in a storable ready-to-use and
      high-throughput-compatible ELISA-type format. At the center of the assay is an
      antibiotic sensor protein whose interaction with specific DNA fragments is
      responsive to a particular class of antibiotics. Binding of biosensor protein to
      the cognate DNA chemically linked to a solid surface is converted into an immuno
      based colorimetric readout correlating with specific antibiotics concentrations.

PMID- 15580577
TI  - Enhanced biotransformations and product recovery in a membrane bioreactor through
      application of a direct electric current.
AB  - The simultaneous enhancement of biotransformation coupled to product recovery,
      purification and concentration is presented. The nitrilase of Rhodococcus
      rhodochrous LL100-21 catalyses the single-step hydrolytic biotransformation of
      benzonitrile to benzoic acid and ammonia. When a direct electric current is
      applied across a bioreactor containing the bacterium and benzonitrile, the
      charged product (benzoic acid) can be removed in situ across an anion exchange
      membrane and recovered in a separate compartment. Over the course of a 24-hour
      biotransformation, benzonitrile was converted to benzoic acid which was
      completely removed from the bioreactor chamber and concentrated 3-fold in a
      separate chamber. The rate of production of benzoic acid increased by 42% when
      the current was applied (0.044 mmol/min/g dry cell weight in the presence of
      current as compared to 0.03 mmol/min/g dry cell weight in its absence). The
      enhanced reaction rate was achieved irrespective of product separation and
      therefore appears to be a direct effect upon the bacterial cells. This process
      has potential for enhanced productivity from biotransformations through a
      simultaneous increase in metabolic activity and in situ product recovery.

PMID- 15580578
TI  - Engineering HlyA hypersecretion in Escherichia coli based on proteomic and
      microarray analyses.
AB  - Escherichia coli is a common host for recombinant protein production for
      biotechnology applications. Secretion to the extracellular media has the
      potential to reduce protein aggregation and to simplify downstream purification.
      However, the complexity of the mechanisms of protein secretion has confounded
      prior attempts to engineer enhanced secretion phenotypes. Here, mutagenesis was
      used to perturb E. coli W3110 cells secreting HlyA via a Type I pathway. An
      activity assay identified a mutant secreting fourfold more active alpha-hemolysin
      than the parent strain. The mutant was characterized using both high-density
      microarrays for mRNA profiling and a proteomics strategy for protein expression.
      The relative mRNA and protein expression levels of tRNA-synthetases were
      decreased in the mutant compared to the parent. A mathematical model of
      prokaryotic translation was used to design a variant of the hlyA gene that
      encodes the same amino acid sequence but uses rare codons to slow the rate of
      translation by altering five bases. Analysis of the parent strain transformed
      with a plasmid containing this variant gene resulted in the recovery of, and
      further improvement upon, the selected hypersecretion phenotype. These results
      present one of the first successful metabolic engineering attempts based on
      molecular information provided by mRNA and protein expression profiling
      approaches and resulting in a phenotype useful to the biotechnology community.

PMID- 15580579
TI  - Wild capuchin monkeys (Cebus libidinosus) use anvils and stone pounding tools.
AB  - We conducted an exploratory investigation in an area where nut-cracking by wild
      capuchin monkeys is common knowledge among local residents. In addition to
      observing male and female capuchin monkeys using stones to pound open nuts on
      stone "anvils," we surveyed the surrounding area and found physical evidence that
      monkeys cracked nuts on rock outcrops, boulders, and logs (collectively termed
      anvils). Anvils, which were identified by numerous shallow depressions on the
      upper surface, the presence of palm shells and debris, and the presence of loose
      stones of an appropriate size to pound nuts, were present even on the tops of
      mesas. The stones used to crack nuts can weigh >1 kg, and are remarkably heavy
      for monkeys that weigh <4 kg. The abundance of shell remains and depressions in
      the anvil surface at numerous anvil sites indicate that nut-cracking activity is
      common and long-enduring. Many of the stones found on anvils (presumably used to
      pound nuts) are river pebbles that are not present in the local area we surveyed
      (except on or near the anvils); therefore, we surmise that they were transported
      to the anvil sites. Ecologically and behaviorally, nut-cracking by capuchins
      appears to have strong parallels to nut-cracking by wild chimpanzees. The
      presence of abundant anvil sites, limited alternative food resources, abundance
      of palms, and the habit of the palms in this region to produce fruit at ground
      level all likely contribute to the monkeys' routine exploitation of palm nuts via
      cracking them with stones. This discovery provides a new reference point for
      discussions regarding the evolution of tool use and material culture in primates.
      Routine tool use to exploit keystone food resources is not restricted to living
      great apes and ancestral hominids.

PMID- 15580580
TI  - Use of gesture sequences in chimpanzees.
AB  - Gestural communication in a group of 19 captive chimpanzees (Pan troglodytes) was
      observed, with particular attention paid to gesture sequences (combinations). A
      complete inventory of gesture sequences is reported. The majority of these
      sequences were repetitions of the same gestures, which were often tactile
      gestures and often occurred in play contexts. Other sequences combined gestures
      within a modality (visual, auditory, or tactile) or across modalities. The
      emergence of gesture sequences was ascribed to a recipient's lack of
      responsiveness rather than a premeditated combination of gestures to increase the
      efficiency of particular gestures. In terms of audience effects, the chimpanzees
      were sensitive to the attentional state of the recipient, and therefore used
      visually-based gestures mostly when others were already attending, as opposed to
      tactile gestures, which were used regardless of whether the recipient was
      attending or not. However, the chimpanzees did not use gesture sequences in which
      the first gesture served to attract the recipient's visual attention before they
      produced a second gesture that was visually-based. Instead, they used other
      strategies, such as locomoting in front of the recipient, before they produced a
      visually-based gesture.

PMID- 15580581
TI  - Comparing maternal styles in bonobos (Pan paniscus) and chimpanzees (Pan
      troglodytes).
AB  - Studies on Cercopithecine primate maternal styles, using factor analysis on a set
      of maternal behaviors, commonly render two factors that describe separate
      dimensions of maternal behavior: protectiveness and rejection. The aims of this
      study were to 1) investigate whether this method for determining maternal styles
      in Cercopithecine species can be applied to bonobos (Pan paniscus) and
      chimpanzees (Pan troglodytes), 2) determine whether they follow the same pattern,
      and 3) assess whether species differences in maternal style are apparent. We
      performed a factor analysis on nine maternal behaviors using data on eight mother
      infant pairs of each species. This resulted in three factors: protectiveness,
      distance, and refusal. Protectiveness is positively correlated with time spent in
      ventral contact, making contact, approaching, and restraining. Distance is
      positively related with breaking contact and leaving. Refusal is positively
      correlated with rejecting and nipple-rejecting. The pattern of protectiveness
      corresponds with the pattern found in Cercopithecine species, suggesting a high
      consistency of this dimension across species and higher taxa. The retention of
      the other two factors indicates that in the Pan species, breaking contact and
      leaving represent another dimension, apart from rejecting and nipple-rejecting,
      which usually fall under one dimension in Cercopithecine species. An
      interspecific comparison of the factor scores for each dimension of maternal
      behavior reveals that, on average, bonobos and chimpanzees score equally on
      protectiveness. Scores on distance increase positively with infant age in
      chimpanzees, and negatively in bonobos, and on average bonobos have higher scores
      on refusal. These interspecies differences in maternal style are discussed in the
      light of interspecies differences in infant development, infant vulnerability to
      aggression, interbirth intervals, and female sociality.

PMID- 15580582
TI  - Demographic parameters and events in wild moustached Tamarins (Saguinus mystax).
AB  - This paper examines demographic events in the context of population structure and
      genetic relationships in groups of wild moustached tamarins (Saguinus mystax). We
      used a combination of long-term behavioral observations and genetic data from a
      total of eight groups from a population in northeastern Peruvian Amazonia. The
      mean group size was 6.0 (range = 4-9), including 2.5 adult males and 1.8 adult
      females. Within-group relatedness was generally high (r = 0.3), and most
      nonbreeding individuals were either natal or closely related to the respective
      same-sex breeder. The mean annual persistence of adults in the groups was 70% and
      68% for males and females, respectively, and the reproductive tenure of one
      breeding pair lasted for at least 6 years. Migrations predominantly occurred
      after stability-disrupting events such as the immigration of new individuals
      and/or the loss of breeding individuals, or when groups were rather large.
      Migrations of both breeding and nonbreeding males and females occurred. Our
      results show that the hypothesis of Ferrari and Lopes Ferrari [Folia
      Primatologica 52:132-147, 1989] that tamarins live in smaller and less stable
      groups with lower relatedness compared to marmosets does not generally hold true.
      In contrast, we found that tamarin groups can consist of predominantly related
      individuals, and are stable as well. It is also apparent that a single
      demographic event can produce a chain of subsequent complex demographic changes.

PMID- 15580583
TI  - Mirrors as environmental enrichment for African green monkeys.
AB  - Stainless steel circular mirrors were employed in an enrichment plan for 105
      singly housed male African green monkeys. We observed 25 randomly selected males
      to measure mirror use and to assess the mirrors' effectiveness as an enrichment
      item. We conducted additional mirror-use surveys on all 105 males using
      fingerprint accumulation as an indicator (rated on a scale of 0 to 4). Use was
      defined as either being in contact with the mirror (contact use (CU)) or looking
      directly into the mirror without contact (non-contact use (NC)). Mirror-use data
      were collected 10 months after the initial introduction of the mirrors and again
      at 16 months. The two time points were compared by paired t-tests. No significant
      difference in use was found between the two data collection points. On average,
      the monkeys used the mirrors 5.2% of the total time intervals recorded
      (approximately 3 min/hr). Results from the five fingerprint-accumulation surveys
      showed that 102 of 105 males (97%) had CU with their mirrors over the survey
      points. Based on the sustained use of the mirrors over a 6-month period, we
      concluded that the mirrors were an effective enrichment tool that the vast
      majority of our monkeys routinely used. Habituation did not appear to occur even
      a year after the mirrors were introduced.

PMID- 15580584
TI  - Hormone profiles and reproductive characteristics in wild female Japanese
      macaques (Macaca fuscata).
AB  - In this study we investigated the reproductive characteristics of wild female
      Japanese macaques (Macaca fuscata fuscata) in 2 nonconsecutive years using
      noninvasive methods to monitor physiological events. We detected ovulation dates
      and ascertained conceptions from fecal hormone profiles. First ovulations
      occurred from middle October to early November in 1997, and from middle to late
      November in 1999. Most females conceived during their first ovarian cycle. On
      average, postconception bleeding occurred 18.4 days after ovulation, and
      menstruation occurred 13.7 days after ovulation. The average gestation length was
      176.3 days. The average degree of facial redness and the percentage of females
      that copulated synchronously changed across the ovarian cycle and peaked in the
      periovulatory period. Although prolonged periods of postconception copulation
      have been reported in previous studies, they did not occur in this study, which
      suggests that such behavior may not be a species-typical characteristic. Female
      fertility varied between the 2 years. The copulation rates of females with no
      infant <1 year of age were 100% (14/14) in 1997 and 45.5% (5/11) in 1999. The
      ovulation rates of the female subjects that we chose for hormonal assays were
      100% (9/9) in 1997 and 50.0% (3/6) in 1999. Th conception rates of these selected
      females were 100% (9/9) in 1997 and 16.7% (1/6) in 1999. The birth rates (the
      number of females that delivered divided by the total number of adult females in
      the troop) were 73.3% (11/15) in 1998 and 6.7% (1/15) in 2000. The modified birth
      rates (the number of females that delivered /the number of adult females with no
      infant <1 year of age) x 100 were 78.6% (11/14) in 1998 and 9.1% (1/11) in 2000.

PMID- 15580585
TI  - Sex differences in sexual partner acquisition, retention, and harassment during
      female homosexual consortships in Japanese macaques.
AB  - Female Japanese macaques (Macaca fuscata) in certain populations are unusual in
      that they exhibit male-typical patterns of mounting behavior and sexual-partner
      preference. The goal of this study was to determine whether female Japanese
      macaques, from one such population, employ male-typical behavioral tactics to
      disrupt existing homosexual consortships, as well as to acquire and retain same
      sex sexual partners. "Harassment" of homosexual consortships occurred when a
      sexually motivated, third-party male or female interrupted a consorting female
      couple by displacing or aggressing them. Sexual harassment was a male-typical
      strategy for disrupting existing homosexual consortships, but was rarely
      performed by females. "Intrusions" occurred when a male or female competitor
      attempted to acquire exclusive access to a female engaged in a homosexual
      consortship by targeting that female as the focus of competition and her partner
      as his/her competitor. "Sexual coercion" occurred when one individual alternately
      sexually solicited and aggressed another individual as part of the same
      behavioral sequence during an intrusion. Males employed consortship intrusions
      and sexual coercion when they attempted to acquire female sexual partners that
      were already engaged in homosexual consortships, but females rarely did so.
      However, females did employ male-typical patterns of aggressive competition and
      sexual coercion to retain same-sex sexual partners when confronted with male
      competitors' attempts to usurp those partners. These results indicate that female
      sexual activity during homosexual consortships is not uniformly "masculine" in
      expression, but rather is a mixture of male- and female-typical behaviors.

PMID- 15580586
TI  - Quantifying remaining forested habitat within the historic distribution of the
      cotton-top tamarin (Saguinus oedipus) in Colombia: Implications for long-term
      conservation.
AB  - Landsat Thematic Mapper (TM) data were used to classify forested areas within the
      historic distribution of the endangered cotton-top tamarin (Saguinus oedipus) in
      Colombia. This species continues to be threatened by habitat destruction, and we
      observed a 31% decrease of the forested habitat within the tamarins' historic
      distribution in 1990-2000. It is estimated that since the establishment of some
      protected areas for cotton-top tamarins and other native Colombian wildlife
      (Parque Nacional Natural Paramillo, Santuario de Fauna y Flora Los Colorados, and
      Reserva Forestal de Montes de Maria), almost 43% of the original forested area
      has been lost. Given that the human population of Colombia increases annually by
      1.6% [Patel, 2002], it is important to target specific areas for tamarin
      protection while creating mitigation strategies to compensate for economic
      growth. The results of this study provide valuable information to assist in the
      long-term development of effective conservation strategies for this endangered
      primate.

PMID- 15580587
TI  - Continuous perfusion microfluidic cell culture array for high-throughput cell
      based assays.
AB  - We present for the first time a microfluidic cell culture array for long-term
      cellular monitoring. The 10 x 10 array could potentially assay 100 different cell
      based experiments in parallel. The device was designed to integrate the processes
      used in typical cell culture experiments on a single self-contained microfluidic
      system. Major functions include repeated cell growth/passage cycles, reagent
      introduction, and real-time optical analysis. The single unit of the array
      consists of a circular microfluidic chamber, multiple narrow perfusion channels
      surrounding the main chamber, and four ports for fluidic access. Human carcinoma
      (HeLa) cells were cultured inside the device with continuous perfusion of medium
      at 37 degrees C. The observed doubling time was 1.4 +/- 0.1 days with a peak cell
      density of approximately 2.5*10(5) cells/cm(2). Cell assay was demonstrated by
      monitoring the fluorescence localization of calcein AM from 1 min to 10 days
      after reagent introduction. Confluent cell cultures were passaged within the
      microfluidic chambers using trypsin and successfully regrown, suggesting a stable
      culture environment suitable for continuous operation. The cell culture array
      could offer a platform for a wide range of assays with applications in drug
      screening, bioinformatics, and quantitative cell biology.

PMID- 15580588
TI  - Combined radiation therapy and dendritic cell vaccine for treating solid tumors
      with liver micro-metastasis.
AB  - BACKGROUND: Tumor metastasis and relapse are major obstacles in combating human
      malignant diseases. Neither radiotherapy alone nor injection of dendritic cells
      (DCs) can successfully overcome this problem. Radiation induces tumor cell
      apoptosis and necrosis, resulting in the release of tumor antigen and danger
      signals, which are favorable for DC capturing antigens and maturation. Hence, the
      strategy of combined irradiation and DC vaccine may be a novel approach for
      treating human malignancies and early metastasis. METHODS: To develop an
      effective combined therapeutic approach, we established a novel concomitant local
      tumor and liver metastases model through subcutaneous (s.c.) and intravenous
      (i.v.) injection. We selected the optimal time for DC injection after irradiation
      and investigated the antitumor effect of combining irradiation with DC
      intratumoral injection and the related mechanism. RESULTS: Combined treatment
      with radiotherapy and DC vaccine could induce a potent antitumor immune response,
      resulting in a significant decrease in the rate of local tumor relapse and the
      numbers of liver metastases. The related mechanisms for this strong antitumor
      immunity of this combined therapy might be associated with the production of
      apoptotic and necrotic tumor antigens and heat shock proteins after irradiation,
      phagocytosis, migration and maturation of DCs, and induction of more efficient
      tumor-specific cytotoxic T lymphocyte activity through a cross-presentation
      pathway. CONCLUSIONS: Co-administration of local irradiation and intratumoral DC
      injection may be a promising strategy for treating radiosensitive tumors and
      eliminating metastasis in the clinic.

PMID- 15580589
TI  - Increased utility in the CNS of a powerful neuron-specific tetracycline
      regulatable adenoviral system developed using a post-transcriptional enhancer.
AB  - BACKGROUND: In previous studies we have found that the tetracycline (Tet)
      regulatable system functions best in recombinant adenoviral (Ad) vectors when the
      Tet transactivators and the Tet-regulatable element (TRE) are incorporated into
      separate viral vectors. However, such a dual vector system is disadvantaged by
      the need to use relatively high titres that may elicit an immune response.
      Therefore, to develop a system that could be used at low titres while mediating
      strong, tightly regulatable gene expression in the central nervous system (CNS),
      we incorporated the woodchuck hepatitis virus post-transcriptional enhancer
      (WPRE) into a neuron-specific Tet-regulatable Ad system. METHODS: The WPRE was
      incorporated into Ad vectors encoding the Tet-Off (tTA) transactivator driven by
      the synapsin-1 and CMV promoters and encoding the TRE driving EGFP expression
      (TRE)-EGFP. RESULTS: The addition of the WPRE to the neuron-specific Tet
      regulatable system mediated a greater than three-fold increase in transgene
      expression in primary hippocampal neurons with no loss of gene regulation. The
      results also showed that the addition of the WPRE enhanced transgene expression
      in the CNS without the loss of neuron specificity and without affecting the
      ability to regulate transgene expression. CONCLUSIONS: We have further developed
      a tetracycline-regulatable neuron-specific expression system such that it can now
      be used at low titres with no loss of transgene expression or ability to regulate
      transgene expression. It should therefore be of significant value to studies
      investigating neuronal gene function and to those seeking to develop effective
      neuronal gene therapy strategies.

PMID- 15580590
TI  - Experimental and computational studies of hydrogen bonding and proton transfer to
      [Cp*Fe(dppe)H].
AB  - The present contribution reports experimental and computational investigations of
      the interaction between [Cp*Fe(dppe)H] and different proton donors (HA). The
      focus is on the structure of the proton transfer intermediates and on the
      potential energy surface of the proton transfer leading to the dihydrogen complex
      [Cp*Fe(dppe)(H2)]+. With p-nitrophenol (PNP) a UV/Visible study provides evidence
      of the formation of the ion-pair stabilized by a hydrogen bond between the
      nonclassical cation [Cp*Fe(dppe)(H2)]+ and the homoconjugated anion ([AHA]-).
      With trifluoroacetic acid (TFA), the hydrogen-bonded ion pair containing the
      simple conjugate base (A-) in equilibrium with the free ions is observed by IR
      spectroscopy when using a deficit of the proton donor. An excess leads to the
      formation of the homoconjugated anion. The interaction with hexafluoroisopropanol
      (HFIP) was investigated quantitatively by IR spectroscopy and by 1H and 31P NMR
      spectroscopy at low temperatures (200-260 K) and by stopped-flow kinetics at
      about room temperature (288-308 K). The hydrogen bond formation to give
      [Cp*Fe(dppe)H]HA is characterized by DeltaH degrees =-6.5+/-0.4 kcal mol(-1) and
      DeltaS degrees = -18.6+/-1.7 cal mol(-1) K(-1). The activation barrier for the
      proton transfer step, which occurs only upon intervention of a second HFIP
      molecule, is DeltaH(not equal) = 2.6+/-0.3 kcal mol(-1) and DeltaS(not equal) = 
      44.5+/-1.1 cal mol(-1) K(-1). The computational investigation (at the DFT/B3 LYP
      level with inclusion of solvent effects by the polarizable continuum model)
      reproduces all the qualitative findings, provided the correct number of proton
      donor molecules are used in the model. The proton transfer process is, however,
      computed to be less exothermic than observed in the experiment.

PMID- 15580591
TI  - Identification and impact of outcome selection bias in meta-analysis.
AB  - The systematic review community has become increasingly aware of the importance
      of addressing the issues of heterogeneity and publication bias in meta-analyses.
      A potentially bigger threat to the validity of a meta-analysis appears relatively
      unnoticed. The within-study selective reporting of outcomes, defined as the
      selection of a subset of the original variables recorded for inclusion in
      publication of trials, can theoretically have a substantial impact on the
      results. A cohort of meta-analyses on the Cochrane Library was reviewed to
      examine how often this form of within-study publication bias was suspected and
      explained some of the evident funnel plot asymmetry. In cases where the level of
      suspicion was high, sensitivity analysis was undertaken to assess the robustness
      of the conclusion to this bias. Although within-study selection was evident or
      suspected in several trials, the impact on the conclusions of the meta-analyses
      was minimal. This paper deals with the identification of, sensitivity analysis
      for, and impact of within-study selective reporting in meta-analysis.

PMID- 15580592
TI  - A comparison of goodness of fit tests for the logistic GEE model.
AB  - Generalized estimating equations have become a popular regression method for
      analysing clustered binary data. Methods to assess the goodness of fit of the
      fitted models have recently been developed. However, evaluations and comparisons
      of these methods are limited. We discuss these methods and develop two additional
      statistics to evaluate goodness of fit. We evaluate the performance of each of
      the statistics with respect to type I error rates and power in a simulation
      study. Guidance is provided regarding appropriate use of the statistics under
      various scenarios.

PMID- 15580594
TI  - High relaxivity confined to a small molecular space: a metallostar-based,
      potential MRI contrast agent.

PMID- 15580593
TI  - Development of a semi-quantitative plate-based alpha-galactosidase gene reporter
      for Schizosaccharomyces pombe and its use to isolate a constitutively active
      Mam2.
AB  - To extend the tools available for biochemical and genetical analysis in the
      fission yeast Schizosaccharomyces pombe we have investigated the development of
      gene reporter systems using the secreted alpha-galactosidase encoded by the Sz.
      pombe ORF SPAC869.07c (CAB60017), which we propose naming Mel1p to reflect its
      structural and functional similarity to MEL1p in Saccharomyces cerevisiae. The
      alpha-galactosidase activity can be monitored in liquid assays and converted the
      colourless substrate 5-bromo-4-chloro-3-indolyl-alpha-D-galactopyranoside (X
      alpha-gal) into an insoluble blue product that was suitable for semi quantitative
      plate-based assays; colonies expressing the highest levels of alpha-galactosidase
      developed the most intense blue colour. Unlike assays based on beta
      galactosidase, the Sz. pombe colonies develop the blue colouration under normal
      growth conditions, avoiding the need to replicate colonies to fresh plates for
      analysis. It is therefore suitable for screening large numbers of colonies. To
      illustrate the use of mel1 as a reporter we linked expression to the sxa2 gene
      promoter to provide a convenient readout for signalling through the pheromone
      response pathway. The sxa2 > mel1 strain identified constitutively active Mam2
      pheromone receptors from a randomly mutagenised library. There was an approximate
      correlation between the intensity of the blue colour developed by each mutant
      colony and its level of constitutive activity and we identified a subset of
      mutants with low constitutive activity that could not have been isolated by a
      previous screen using nutritional selection. The mel1 alpha-galactosidase
      activity identified and characterised in this study can be easily adapted to
      provide a gene reporter for many biological processes and is a new addition to
      the research tools available in Sz. pombe.

PMID- 15580596
TI  - Application of DNA pooling to large studies of disease.
AB  - Large collections of individuals are required to investigate the association of
      commonly occurring genetic variation with disease. The laboratory assessment of
      one form of variation, single nucleotide polymorphisms, is costly in time and
      DNA. Robust statistical approaches are developed to allow the successful
      implementation of a recently described laboratory method for rapidly estimating
      allele frequency using pools of DNA. A substantial reduction in Type I error is
      demonstrated using simulation, through the incorporation of measurement error
      into confidence limits for a case-control study, illustrated on a case-control
      study of acute leukaemia in adults. A method for creating multiple sub-pools is
      described which will allow large studies, such as the proposed U.K. Biobank, to
      take advantage of this method. Furthermore, a set-based logistic regression is
      presented which allows the investigation of joint effects and interactions with
      other genes or environmental factors.

PMID- 15580597
TI  - Choice of time-scale in Cox's model analysis of epidemiologic cohort data: a
      simulation study.
AB  - Cox's regression model is widely used for assessing associations between
      potential risk factors and disease occurrence in epidemiologic cohort studies.
      Although age is often a strong determinant of disease risk, authors have
      frequently used time-on-study instead of age as the time-scale, as for clinical
      trials. Unless the baseline hazard is an exponential function of age, this
      approach can yield different estimates of relative hazards than using age as the
      time-scale, even when age is adjusted for. We performed a simulation study in
      order to investigate the existence and magnitude of bias for different degrees of
      association between age and the covariate of interest. Age to disease onset was
      generated from exponential, Weibull or piecewise Weibull distributions, and both
      fixed and time-dependent dichotomous covariates were considered. We observed no
      bias upon using age as the time-scale. Upon using time-on-study, we verified the
      absence of bias for exponentially distributed age to disease onset. For non
      exponential distributions, we found that bias could occur even when the covariate
      of interest was independent from age. It could be severe in case of substantial
      association with age, especially with time-dependent covariates. These findings
      were illustrated on data from a cohort of 84,329 French women followed
      prospectively for breast cancer occurrence. In view of our results, we strongly
      recommend not using time-on-study as the time-scale for analysing epidemiologic
      cohort data.

PMID- 15580598
TI  - Controversies concerning randomization and additivity in clinical trials.
AB  - 'As ye randomise so shall ye analyse', is one way of describing Fisher's defence
      of randomization. Yet, when it comes to clinical trials we nearly always
      randomize but we rarely analyse the way we randomize and Fisher himself was no
      exception. Two controversies involving Fisher in the 1930s are discussed: one
      with Neyman concerning additivity and the other with Student concerning
      randomization. Their relevance today is considered, as is whether randomization
      inference in clinical trials is dead and whether modelling rules the day, whether
      minimization is an acceptable procedure and to what extent trialists confuse
      experiments with surveys. It will be maintained that a number of different
      possible purposes of clinical trials have been confused because in the case of
      the general linear model, under strong additivity, they can all be satisfied by a
      single analysis. More generally, however, this is not the case.

PMID- 15580599
TI  - Efficiency of the cross-over design: an empirical estimation.
AB  - The aim of the present study is to estimate the relative efficiency of cross-over
      clinical trials as compared to the corresponding parallel designs. A MEDLINE
      'full text' search covering years 2000-2003 over the word 'cross-over' identified
      40 true cross-over studies with the parametric approach published in leading
      medical journals. A parallel design is expected to need, in order to achieve the
      same power, between 4 and 10 times more subjects than the corresponding cross
      over design, meaning that cost of a parallel design can be between 2 and 5 times
      higher. There is a high proportion (18/40 = 45.0 per cent) of cross-over studies
      recently published in leading medical journals that, disregarding the CONSORT
      recommendations, does not provide estimates for the effect size and its standard
      error, hence, not allowing for the posterior use of the data in a meta-analysis.

PMID- 15580601
TI  - Using generalized additive models to reduce residual confounding.
AB  - Traditionally, confounding by continuous variables is controlled by including a
      linear or categorical term in a regression model. Residual confounding occurs
      when the effect of the confounder on the outcome is mis-modelled. A continuous
      representation of a covariate was previously shown to result in a less biased
      estimate of the adjusted exposure effect than categorization provided the
      functional form of the covariate-outcome relationship is correctly specified.
      However, this is rarely known. In contrast to parametric regression, generalized
      additive models (GAM) fit a smooth dose-response curve to the data, without
      requiring a priori knowledge of the functional form. We used simulations to
      compare parametric multiple logistic regression vs its non-parametric GAM
      extension in their ability to control for a continuous confounder. We also
      investigated several issues related to the implementation of GAM in this context,
      including: (i) selecting the degrees of freedom; and (ii) alternative criteria
      for inclusion/exclusion of the potential confounder and for choosing between
      parametric and non-parametric representation of its effect. The impact of the
      shape and strength of the confounder-disease association, sample size, and the
      correlation between the confounder and exposure were investigated. Simulations
      showed that when the confounder has a non-linear association with the outcome,
      compared to a parametric representation, GAM modelling (i) reduced the mean
      squared error for the adjusted exposure effect; (ii) avoided inflation of the
      type I error for testing the exposure effect. When the true confounder-outcome
      relationship was linear, GAM performed as well as the parametric logistic
      regression. When modelling a continuous exposure non-parametrically, in the
      presence of a continuous confounder, our results suggest that assuming a linear
      effect of the confounder and focussing on the non-linearity of the exposure
      outcome relationship leads to spurious findings of non-linearity: joint non
      linear modelling is necessary. Overall, our results suggest that the use of GAM
      to reduce residual confounding offers several improvements over conventional
      parametric modelling.

PMID- 15580602
TI  - The graft-versus-leukaemia effect after allogeneic bone-marrow transplantation:
      assessment through competing risks approaches.
AB  - In failure time studies involving a chronic disease such as cancer, data often
      focus on one or more non-fatal events, in addition to survival, to describe the
      course of the disease. In the example of allogeneic bone marrow transplantation
      in leukaemic patients, acute graft-versus host disease (aGvHD), relapse and death
      were taken as the reported events, and we focused on testing the existence of
      graft-versus-leukaemia (GvL) effect, i.e. that the occurrence of aGvHD modifies
      the probability of relapse. One of the weaknesses of the standard competing risks
      models is their inability to model secondary relapses. We thus derived, from two
      competing risks models, two estimators of cumulative incidence functions of
      primary and secondary relapses, as well as statistics to test the GvL effect. The
      approach is illustrated by application to a data set from a cohort of 442
      children with acute leukaemia who received an unrelated transplant.

PMID- 15580603
TI  - The analysis of peak expiratory flow data using a three-level hierarchical model.
AB  - Peak expiratory flow (PEF) is a measure commonly used in clinical practice and
      research for respiratory diseases such as asthma. In research, PEF is usually
      recorded in a diary for a 2-week period with two or more measurements per day.
      Interest may lie in whether certain groups of individuals tend to have higher or
      lower PEF. In addition the variability of PEF may be of interest as, for example,
      asthmatics tend to have more variable airways. In this paper we develop a three
      level hierarchical model that can simultaneously model the mean level and
      variability of PEF. The variability is broken down into three components, between
      subject variability, between-day within-subject variability, and within-day
      within-subject variability. The latter two components are of specific clinical
      interest. We fit both classical and Bayesian models. The Bayesian models have the
      advantage of taking the uncertainty in the variance component estimates into
      account when estimating the standard errors of the fixed effects. In addition,
      the Bayesian models provide an intuitive and simple way to investigate the within
      subject variance components.

PMID- 15580604
TI  - Sequential tests for gene-environment interactions in matched case-control
      studies.
AB  - The sample size necessary to detect a significant gene x environment interaction
      in an observational study can be large. For reasons of cost-effectiveness and
      efficient use of available biological samples we investigated the properties of
      sequential designs in matched case-control studies to test for both non
      hierarchical and hierarchical interactions. We derived the test statistics Z and
      V and their characteristics when applied in a two-sided triangular test. Results
      of simulations show good agreement with theoretical values for V and the type I
      error. Power values were larger than their theoretical values for very large
      sample sizes. Median gain in efficiency was about 27 per cent. For a 'rare'
      phenotype gain in efficiency was larger when the alternative hypothesis was true
      than under the null hypothesis. Sequential designs lead to substantial efficiency
      gains in tests for interaction in matched case-control studies.

PMID- 15580606
TI  - Levodopa-dyskinesia incidence by age of Parkinson's disease onset.
AB  - We assessed the 5-year risk of levodopa-induced dyskinesias by age of Parkinson's
      disease (PD) onset in a population-based cohort. The medical records linkage
      system of the Rochester Epidemiology project was used to identify residents of
      Olmsted County, Minnesota, with incident PD for the period 1976 through 1990. In
      this population-based study, the 5-year dyskinesia incidence declined with age.
      With PD onset after 70 years of age, the incidence was 16%. With onset from 40 to
      59 years of age, the incidence was higher at 50%. These incidence data may
      overestimate the functional importance, because patients with minimal or
      reversible dyskinesias were counted.

PMID- 15580607
TI  - Trial of subtherapeutic pergolide in de novo Parkinson's disease.
AB  - The effect of pergolide 25 mug twice daily on levodopa initiation was assessed in
      a randomized, placebo-controlled, parallel group, double-blind multicenter trial
      in 106 untreated early Parkinson's disease patients. The primary endpoint of mean
      time until levodopa was 520 days (95% confidence interval [CI], 422-618 days) for
      pergolide versus 434 days (95% CI, 358-609 days) for placebo. However, this
      increase of 86 days for pergolide was not statistically significant. The wash-in
      effect of pergolide was significant at 6 weeks (change in mean Unified
      Parkinson's Disease Rating Scale [UPDRS] 2 and 3 was -0.1 [95% CI, -1.4 to 1.3]
      for pergolide vs. 2.2 [95% CI, 1.1-3.3] for placebo). At termination, the change
      from baseline in mean UPDRS 2 and 3 score was 11.4 (95% CI, 8.8-14) for pergolide
      and 14.6 (95% CI, 12-17.2) for placebo (P=0.08). There was no significant change
      in UPDRS 2 and 3 for the 83 patients achieving the planned 4-week washout at
      termination (pergolide 1.2 [95% CI, -0.8 to 3.2] vs. placebo 0.0 [95% CI, -1.6 to
      1.6]. Adverse events were infrequent and occurred equally for pergolide and
      placebo. The study shows no evidence of a neuroprotective effect but indicates a
      mild symptomatic benefit from pergolide at a dose normally considered
      subtherapeutic.

PMID- 15580608
TI  - Potassium transport at the plasma membrane of the food spoilage yeast
      Zygosaccharomyces bailii.
AB  - Zygosaccharomyces bailii is a commercially important spoilage yeast capable of
      growth at low pH in the presence of weak organic acid preservatives, such as
      benzoic acid. A patch-clamp electrophysiological analysis of plasma membrane K+
      transport revealed a high conductance pathway for low-affinity K+ uptake. In
      contrast to the equivalent K+ transporter in Saccharomyces cerevisiae, this
      system remained operative at low extracellular pH and may therefore facilitate K+
      uptake in K(+)-rich and acidic beverages. Benzoate inhibited growth, increased
      intracellular K+ content, yet decreased the magnitude of the K+ uptake
      conductance; specifically, the hyperpolarization-activated inwardly-rectifying
      component was reduced. It is proposed that this adaptation helps maintain a
      hyperpolarized membrane voltage to effect continued ATPase-mediated H+ extrusion
      and so combat preservative-induced cytosolic acidosis. Again in contrast to S.
      cerevisiae, the K+ conductance was relatively insensitive to increased
      extracellular Ca2+. Paradoxically (and unlike S. cerevisiae) increasing
      extracellular Ca2+ inhibited growth, suggesting a simple expedient to limit
      spoilage by Z. bailii.

PMID- 15580610
TI  - Methadone for refractory restless legs syndrome.
AB  - Most cases of restless legs syndrome (RLS) initially respond well to dopaminergic
      agonists. However, an unknown percentage of patients is intolerant of
      dopaminergic adverse events, initially or subsequently refractory, or develops
      limiting augmentation. We administered methadone 5 to 40 mg/day (final dose, 15.6
      +/- 7.7) to 29 RLS patients who failed dopaminergics. They were currently taking
      or had previously tried 5.9 +/- 1.7 (range, 3-9) different medications for RLS
      and 2.9 +/- 0.8 (range, 2-4) different dopaminergics. Of the 27 patients who met
      inclusion criteria, 17 have remained on methadone for 23 +/- 12 months (range, 4
      44 months) at a dose of 15.5 +/- 7.7 mg/day; 2 dialysis RLS patients died while
      on methadone, and 8 stopped the treatment (5 for adverse events, 2 for lack of
      efficacy, and 1 for logistical reasons). All patients who remain on methadone
      report at least a 75% reduction in symptoms, and none have developed
      augmentation. Methadone should be considered in RLS patients with an
      unsatisfactory dopaminergic response.

PMID- 15580611
TI  - Critical roles of CD146 in zebrafish vascular development.
AB  - In this report, we use zebrafish as a model system to understand the importance
      of CD146 in vascular development. Endothelial-specific expression of CD146 was
      verified by whole-mount in situ hybridization. Suppression of CD146 protein
      expression by antisense morpholino oligonucleotides (MO) resulted in poorly
      developed intersomitic vessels (ISVs). In CD146 morphants, we observed a lack of
      blood flow through the ISV region, despite that fluorescence microangiography
      showed that the ISVs were present. This finding suggests that the lumens of the
      developing ISVs may be too narrow for proper circulation. Additionally,
      remodeling of the caudal vein plexus into functional vascular tubes appeared to
      be affected. Suppression of CD146 protein expression resulted in a circulation
      shunt that caused the circulation to by-pass part of the caudal artery/vein
      system. The same vascular defects were recapitulated by using a second morpholino
      oligonucleotide. This morphant expressed a truncated CD146 protein with amino
      acids V32 to T57 at the N terminus deleted in an in-frame manner. This region,
      therefore, is likely to contain elements critical for CD146 function. This study
      provides the first in vivo functional assessment of CD146 in embryonic
      development by showing that knockdown of CD146 protein expression severely
      hinders vascular development in zebrafish.

PMID- 15580613
TI  - T-box genes and heart development: putting the "T" in heart.
AB  - Members of the T-box gene family (Tbx) are essential for normal heart
      development, and mutations in human TBX genes cause congenital cardiovascular
      malformations. T-box genes have been implicated in early cardiac lineage
      determination, chamber specification, valvuloseptal development, and
      diversification of the specialized conduction system in vertebrate embryos. These
      genes include Tbx1, Tbx2, Tbx3, Tbx5, Tbx18, and Tbx20, all of which exhibit
      complex temporal spatial regulation in developing cardiac structures. Less is
      known about T-box genes in invertebrate heart development, but multiple T-box
      genes are expressed in Drosophila cardiac lineages. The molecular hierarchies and
      developmental processes controlled by T-box genes in the heart are the focus of
      this review.

PMID- 15580614
TI  - Roles of JUMONJI in mouse embryonic development.
AB  - Cardiac development is a complex biological process requiring the integration of
      cell specification, differentiation, migration, proliferation, and morphogenesis.
      Although significant progress has been made recently in understanding the
      molecular basis of cardiac development, mechanisms of transcriptional control of
      cardiac development remain largely unknown. In search for the developmentally
      important genes, the jumonji gene (jmj) was identified by gene trap technology
      and characterized as a critical nuclear factor for mouse embryonic development.
      Jmj has been shown to play important roles in cardiovascular development, neural
      tube fusion process, hematopoiesis, and liver development in mouse embryos. The
      amino acid sequence of the JUMONJI protein (JMJ) reveals that JMJ belongs to the
      AT-rich interaction domain transcription factor family and more recently has been
      described as a member of the JMJ transcription factor family. Here, we review the
      roles of jmj in multiple organ development with a focus on cardiovascular
      development in mice.

PMID- 15580615
TI  - Bilateral subthalamic nucleus deep brain stimulation in a patient with cervical
      dystonia and essential tremor.
AB  - The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well
      established in Parkinson's disease, but experience with STN DBS in other movement
      disorders is limited. We report on a patient with medically refractory cervical
      dystonia and essential tremor resulting in dystonic head tremor and action tremor
      of the hands who obtained complete tremor suppression and near resolution of her
      cervical dystonia with bilateral STN stimulation. The results in this case
      demonstrate that STN DBS can dramatically improve dystonia and tremor in
      nonparkinsonian movement disorders.

PMID- 15580616
TI  - Ephrin signaling in vivo: look both ways.
AB  - Eph receptors and ephrins have captured the interest of the developmental biology
      community in recent years for their pleiotropic functions during embryogenesis.
      Loss-of-function studies using various animal models have demonstrated the
      involvement of Ephs and ephrins in many aspects of embryogenesis including
      segmentation, neural crest cells migration, angiogenesis, and axon guidance. An
      essential property of this signaling pathway is the ability of both Ephs and
      ephrins to behave as receptors or ligands and their consequent cell autonomous
      and nonautonomous mode of action. While many reports did not discriminate between
      Eph autonomous signaling (forward) and ephrin autonomous signaling (reverse),
      recent genetic and in vivo studies have shown that both forward and reverse
      signaling play important roles during embryogenesis.

PMID- 15580617
TI  - Preferences for different methods of communicating information regarding adjuvant
      chemotherapy for breast cancer.
AB  - Many patients play an active role in determining their cancer treatments, and the
      communication of medical information influences patient decision-making. This
      study examined participants' preferences between various methods of communicating
      quantitative risks and benefits of adjuvant chemotherapy. Using clinical
      vignettes, participants were first asked to decide whether or not to endorse
      chemotherapy and were subsequently asked about their preferences for the methods
      used to communicate the risks and benefits. Participants preferred the absolute
      survival benefit method over negatively framed methods, such as relative or
      absolute risk reduction. We also present analysis of qualitative data which
      supports the conclusions drawn from quantitative analyses. In summary, the
      absolute survival benefit was shown to be the superior method of communicating
      quantitative risks and benefits of chemotherapy. Failure to use clear and concise
      methods of communicating quantitative risk and benefit information may compromise
      efforts to obtain informed consent for treatment.

PMID- 15580618
TI  - Disparities in the recording of Parkinson's disease on death certificates.
AB  - Although little is known regarding potential socioeconomic or racial bias in the
      recording of Parkinson's disease (PD) on death certificates, studies of
      incidence, prevalence, and the etiology of PD frequently rely on this type of
      data. A national population-based survey was linked to death certificate data to
      investigate the concordance of PD reported on death certificates for persons
      reporting PD during life. Logistic regression was used to identify independent
      factors associated with differential reporting of PD at death. Among decedents
      with PD reported during life, 54.8% had PD recorded on the death certificate.
      Nearly 70% of persons in higher income categories had PD recorded at death
      compared to 35.4% for those earning $10,000 or less. Age and gender adjusted odds
      of having PD recorded at death was 2.3 (1.1-3.9), for those with an annual income
      of $35,000 or more. Income differences remain significant in multivariable models
      after controlling for age, gender, race, census region, family size, rural
      residence, and number of chronic medical conditions. In conclusion, this study
      found socioeconomic bias in the reporting of PD at death. This bias is large
      enough to confound death certificate-based investigations of incidence,
      prevalence, and risk factors that differ across socioeconomic strata.

PMID- 15580620
TI  - Altered intracellular sorting signals do not influence the efficacy of genetic
      melanoma vaccines incorporating helper determinants in mice.
AB  - BACKGROUND: A genetic melanoma vaccine consisting of cDNA encoding the model self
      antigen tyrosinase-related protein 2 (TRP2) fused in-frame to the immunogenic
      enhanced green fluorescent protein (EGFP) was able to break immune tolerance and
      stimulate CD8+ T cells in vivo. In the present study we investigated whether
      alteration of the intracellular antigen localization as a result of the linkage
      with immune-enhancing helper proteins affects the resulting immune response.
      METHODS: Expression plasmids and recombinant adenoviruses were constructed
      encoding various fusion proteins with different intracellular sorting signals
      which direct the antigen to the cytosol, the endoplasmic reticulum or the
      endosomal compartments. Genetic immunization of C57BL/6 mice was performed with
      all constructs using particle-bombardment of the skin and injection of
      recombinant adenoviruses. The resulting immune response was analyzed using
      ELISPOT and tumor rejection assays. RESULTS: Induction of TRP2-specific CD8+ T
      cells in vivo and autoimmune-mediated destruction of melanocytes in the bombarded
      area of the skin were observed with all constructs expressing fusion proteins
      between TRP2 and EGFP. Importantly, injections of the different recombinant
      adenoviruses all mediated protective immunity against transplanted B16 melanoma
      cells. CONCLUSIONS: Altered intracellular sorting signals do not significantly
      influence the efficacy of genetic melanoma vaccines incorporating helper
      determinants in our model system. These results further support the concept that
      linkage of immunogenic helper sequences can be successfully applied for antigen
      specific immunotherapy of melanoma and provide a scientific basis for the
      translation of this strategy in future clinical applications.

PMID- 15580619
TI  - Metalloprotease-disintegrin ADAM8: expression analysis and targeted deletion in
      mice.
AB  - ADAM8 (a disintegrin and metalloprotease 8, also referred to as MS2/CD156a) is a
      membrane-anchored metalloprotease that was first identified in a macrophage cell
      line and has been implicated in neurodegenerative diseases. Here, we evaluated
      the expression of ADAM8 during mouse development and generated mice lacking ADAM8
      (Adam8-/- mice). During early mouse development, ADAM8 is expressed by maternal
      cells in the decidua and by trophoblast derivatives of the embryo but not in the
      derivatives of the inner cell mass. At later stages, prominent expression of
      ADAM8 is seen in the embryo proper, in the gonadal ridge, thymus, developing
      cartilage and bone, brain and spinal cord, and in the mesenchyme in close
      proximity to the branch point between the jugular vein and developing lymphatic
      vessels. Examination of Adam8-/- mice, however, revealed no major defects in
      these or other structures during development or in adult tissues and no evident
      pathological phenotypes.

PMID- 15580621
TI  - Mph2 expression in germinal zones of the mouse brain.
AB  - The telencephalon develops from a seemingly homogeneous population of precursor
      cells that generates neurons with divergent properties and cell fates. An
      important question concerns the genetic control of cell states belonging to
      different generations. Mph2 was identified by serial analysis of gene expression
      as a differentially expressed gene during cortical development. Belonging to the
      Polycomb group, Mph2 may be involved in transcriptional repression of cell states
      from one generation to the next. Here, we use in situ hybridization to determine
      the spatial localization of Mph2 expression in the developing nervous system.
      Mph2 expression evident in proliferating precursor cell populations in the
      developing mouse brain such as the ventricular zones of the cortex and ganglionic
      eminences as well as in mature structures such as the granule cell layer of the
      adult dentate gyrus and cerebellum indicates a role for Mph2 in both the
      developing and adult brain.

PMID- 15580622
TI  - Differential expression of tyrosinated tubulin in Spisula solidissima polar
      bodies.
AB  - The C-terminus of alpha-tubulin can be reversibly modified by a specific tyrosine
      ligase to yield an isoform known as Tyr-tubulin. Tyr-tubulin is typically found
      in more dynamic microtubule arrays such as the mitotic spindle, as opposed to
      stable structures like centrioles and flagella. In developing systems, it is
      expressed in relatively undifferentiated, proliferative cell types but is
      replaced by detyrosinated (Glu-) tubulin during differentiation. We found Tyr
      tubulin highly enriched in a single polar body of Spisula solidissima embryos.
      Quantitation of DNA content by Hoechst staining indicates that polar body 1 (with
      twice the DNA content of polar body 2) is the Tyr-tubulin-positive cell. Other
      than the apoptosis marker caspase, this is, to our knowledge, the first
      distinguishing marker antigen for polar bodies, particularly for one polar body
      vs. another. This localization of Tyr-tubulin is unlikely to be a byproduct of
      the meiotic process itself, because it arises after ejection of both polar bodies
      is complete. Although polar bodies are typically thought of as a terminally
      differentiated vestige of meiosis, the localization of this more dynamic tubulin
      isoform suggests an active role in early development.

PMID- 15580623
TI  - Repression of fibroblast growth factor receptor 1 gene expression by E2F4 in
      skeletal muscle cells.
AB  - Fibroblast growth factor receptor 1 (FGFR1) gene expression is positively and
      negatively regulated during muscle differentiation. We recently reported that
      FGFR1 gene expression was up-regulated by Sp transcription factors in
      proliferating myoblasts. However, the mechanism of down-regulation of this gene
      during differentiation is unknown. We have identified the transcription factor
      E2F4 as a negative regulator of FGFR1 gene expression. Immunodetection studies
      revealed that endogenous E2F1 and E2F2 proteins were cytoplasmic in myoblasts and
      myotubes, whereas E2F4 was abundant in the nuclei of both. Upon overexpression,
      E2F4 repressed FGFR1 promoter activity in a dose-dependent manner in myoblasts
      and Drosophila SL2 cells, and mutation of the E2F4 binding site increased FGFR1
      promoter activity and reduced E2F4-mediated repression. Gel shift assays detected
      E2F4 binding to a synthetic FGFR1 E2F4 binding site and chromatin
      immunoprecipitation assays detected E2F4 binding to the endogenous FGFR1 promoter
      in proliferating myoblasts and myotubes. The results indicate that FGFR1 promoter
      activity in skeletal muscle cells is repressed by E2F4.

PMID- 15580624
TI  - Effects of genetic background on cardiovascular anomalies in the Ts16 mouse.
AB  - To investigate the genetic contribution to phenotypic variability in aneuploidy,
      we generated mice with trisomy 16 (Ts16) by mating [Rb(6.16)24Lub x
      Rb(16.17)7Bnr]F1 males with females from four inbred strains, BALB/cJ, C3H/HeJ,
      C57BL/6J, and DBA/2J. Among the four Ts16 strains that were generated, there were
      no significant differences in survival, weight, or length relative to euploid
      control littermates at either embryonic day (E) 14.5 or E17.5. All Ts16 fetuses
      at E14.5 had edema that ranged from mild to severe, increased amniotic fluid
      volume, and a thickened neck. At E17.5, Ts16 fetuses exhibited two distinct
      phenotypes, one with an edematous morphology and the other runt-like. None of
      these gross morphological abnormalities was strain-specific either in occurrence
      or frequency. At E10.5, there were pharyngeal arch artery (PAA) anomalies in all
      Ts16 embryos on the C3H/HeJ background, but none in trisomics on the other three
      backgrounds. However, at E17.5, there was in addition to ventricular and
      atrioventricular septal defects, a high frequency of aortic arch defects in Ts16
      fetuses, irrespective of genetic background. Taken together, these findings
      indicate that there are at least two mechanistic responses to the presence of
      three copies of mouse chromosome 16 in the modeling of the cardiovascular system:
      one, development of PAA defects, is strongly influenced by genetic background;
      but the second, development of aortic arch anomalies in the absence of
      preexisting PAA anomalies, is not.

PMID- 15580625
TI  - Molecular characterization and developmental expression pattern of the chicken
      apolipoprotein D gene: implications for the evolution of vertebrate lipocalins.
AB  - The insect Lazarillo and the mammalian apolipoprotein D (ApoD) are orthologous
      members of the lipocalin protein family. We report the cloning and embryonic
      expression of chicken ApoD, the first molecularly characterized nonmammalian
      ApoD. We also report the ApoD expression in mouse during postnatal development
      and some novel aspects of the expression of the paralogous lipocalin
      prostaglandin D-synthase (PGDS) and discuss these results in view of the
      lipocalin family evolution in vertebrates. ApoD is expressed in subsets of
      central nervous system (CNS) neurons and glia during late chicken embryogenesis.
      Contrary to mouse ApoD, no expression appears in neural crest-derived cephalic
      mesenchyme and blood vessel pericytes. Also, ApoD is expressed in developing
      chicken feathers. These expressions are corroborated by quantitative reverse
      transcriptase-polymerase chain reaction profiles. ApoD is expressed during mouse
      postnatal development in a subset of CNS neurons, astrocytes and
      oligodendrocytes, but also in meninges and pericytes. Chicken PGDS is expressed
      in brain meninges and perivascular cells. Our results suggest that the amniote
      last common ancestor expressed ApoD and PGDS in the brain during embryogenesis.
      ApoD appears restricted to ectodermal derivatives, whereas PGDS is expressed by
      derivatives of the three germ layers.

PMID- 15580626
TI  - Identification of a novel type II classical cadherin: rat cadherin19 is expressed
      in the cranial ganglia and Schwann cell precursors during development.
AB  - To identify a novel type II classical cadherin, we searched the genome database
      and found rat cadherin19 (cad19) with high similarity to human cadherin19. We
      also found nucleotide sequences corresponding to rat cad19 in mouse and chicken
      genomes. In situ hybridization of rat cad19 revealed that rat cad19 mRNA was
      initially expressed in cephalic neural crest cells, and then in the cranial
      ganglia, migrating trunk neural crest cells, the nascent dorsal root ganglia, and
      the sympathetic ganglia. Expression of cad19 overlapped with that of neural crest
      markers, including Sox10 and AP-2, but cad19 expression was confined to
      subpopulations of the neural crest-derived cells, those typically observed in the
      satellite glia at the periphery of the ganglia and Schwann cell precursors along
      the peripheral nerves. cad19 mRNA was not detected in cells expressing Phox2b, an
      epibranchial placode-derived neurons, nor in those expressing neuronal markers
      such as Hu protein. These observations suggest that cad19 is expressed in neural
      crest-derived, non-neuronal cells. Although the expression of cad19 mRNA
      persisted in Schwann cell precursors at E14.5, it was no longer detected in
      maturing Schwann cells at later stages. These results suggest that cad19 is an
      evolutionarily conserved cadherin and may be involved in the early development of
      Schwann cells in the peripheral nervous system.

PMID- 15580627
TI  - Sudden failure of dual channel pulse generators.
AB  - We report a series of four sudden hardware failures in dual channel pulse
      generators implanted for chronic stimulation of the subthalamic nucleus in the
      treatment of Parkinson's disease. In all cases, a sudden and severe deterioration
      of the patient's neurological condition occurred with symptoms similar to those
      present before surgery. In all cases, destructive analysis of the generator
      revealed a fracture of the wire bonds connecting the battery to the hybrid
      (electronic) part of the pulse generator. This fracture led to repeated Power On
      Resets, bringing the parameter settings back to default (factory settings). As a
      cause, we propose that relative movements between the hybrid and the battery led
      to low cycle fatigue fractures due to insufficient stiffness of the device. That
      three of four failures occurred when the implant was in the infracostal region
      makes it likely that the fractures depend on the mechanical stress applied to the
      device. The efficacy of the therapy resumed immediately after device replacement.
      As a corrective measure, the manufacturer has added epoxy between both
      components, increasing significantly the stiffness of the device.

PMID- 15580628
TI  - Cellular invasion of the chicken corneal stroma during development: regulation by
      multiple matrix metalloproteases and the lens.
AB  - Avian corneal development requires cellular invasion into the acellular matrix of
      the primary stroma. Previous results show that this invasion is preceded by the
      removal of the fibril-associated type IX collagen, which possibly stabilizes
      matrices through interfibrillar cross-bridges secured by covalent crosslinks. In
      the present study, we provide evidence for the expression of three matrix
      metalloproteinases (MMPs) in early corneas, two of which act cooperatively to
      selectively remove type IX collagen in situ. In organ cultures, MMP inhibitors
      (either TIMP-2 or a synthetic inhibitor) resulted in arrested development, in
      which collagen IX persisted, and the stroma remained compact and acellular. We
      also show that blocking covalent crosslinking of collagen allows for cellular
      invasion to occur, even when the removal of type IX collagen is prevented. Thus,
      one factor regulating corneal invasion is the physical structure of the matrix,
      which can be modified by either selective proteolysis or reducing interfibrillar
      cross-bridges. We also detected another level of regulation of cellular invasion
      involving inhibition by the underlying lens. This block, which seems to influence
      invasive behavior independently of matrix modification, is a transient event that
      is released in ovo just before invasion proceeds.

PMID- 15580629
TI  - Transcriptional tumor-selective promoter targeting of E. coli purine nucleoside
      phosphorylase for pancreatic cancer suicide gene therapy.
AB  - BACKGROUND: Pancreatic cancer remains a rapidly fatal disease. Suicide gene
      therapy has been shown to be an effective tool for pancreatic tumor cell
      destruction, but a cell-specific gene delivery is required to limit host
      toxicity. The objective of this study was both to design recombinant vectors in
      which the suicide gene E. coli purine nucleoside phosphorylase (ePNP) is under
      the control of either CEA or MUC1 promoter sequences and to investigate on
      experimental pancreatic carcinomas the selective killing effects of the
      conditional ePNP/prodrug (MePdR) system. METHODS: Transcriptional activities of
      CEA and MUC1 promoter sequences were analyzed using luciferase reporter gene
      constructions. Thereafter, recombinant vectors expressing ePNP under control of
      the most promising pCEA and pMUC1 sequences were designed and used to establish
      stable tumor cell transfectants from two human pancreatic cell lines,
      respectively tumor-marker positive (BxPc3) or negative (Panc-1), then applied for
      in vitro and in vivo experiments. RESULTS: Transient experiments indicated that
      CEA and MUC1 promoter sequences confer specificity while preserving high
      transcriptional activities. The MePdR treatment induced a high in vitro
      cytotoxicity on the sole CEA- and MUC1-producing cell lines (i.e. BxPc3-CEA and 
      MUC1/ePNP). In the same way, prodrug treatment induced a significant tumor
      regression on the sole tumor-marker-positive BxPc3 xenografts, whilst the Panc1
      CEA and -MUC1/ePNP tumors were not affected. CONCLUSIONS: These data confirm and
      extend the antitumor efficacy of the ePNP/MePdR killing system and demonstrate
      the feasibility of the transcriptional targeting strategy under tumor marker
      promoter control and thereby a preferential killing of CEA- and MUC1-producing
      pancreatic tumor cells. Thus, efficient in vivo gene delivery and transcriptional
      targeting constitute the major future clinical challenge for a selective
      pancreatic cancer suicide gene strategy.

PMID- 15580630
TI  - Phenotypic analyses of mouse embryos with ubiquitous expression of Oct4: effects
      on mid-hindbrain patterning and gene expression.
AB  - Oct4 is a transcription factor that has been associated with pluripotency and
      fate determination in the initial cell lineages of mammals. On the other hand,
      Pou2, the ortholog of Oct4 in zebrafish, serves additional later functions during
      brain development acting as a differentiation switch. In mice, Oct4 is expressed
      throughout the neural plate of embryos until embryonic day (E) 8.0. In this
      study, we produced transgenic mouse embryos that ubiquitously express Oct4 and
      analyzed the consequences during development. We show that, at E8.0, a higher
      dosage of Oct4 in the neuroectoderm is sufficient to transiently alter mid
      hindbrain patterning and produced a strong up-regulation of Pax2, indicating that
      Oct4 can regulate this gene in vivo. After E9.5, ectopic Oct4 in this region
      produced cell death and affected the development of the forebrain, suggesting
      that, at these later stages, Oct4 down-regulation is necessary for normal
      development to proceed. The phenotype of the transgenic embryos was also
      accompanied with an increase of Fgf8 expression in several of its endogenous
      domains, suggesting the possibility that Oct4 can participate in the regulation
      of expression of this ligand. Our observations support the hypothesis that Oct4,
      like zebrafish Pou2, has a conserved function during early brain patterning in
      mouse.

PMID- 15580632
TI  - Quantitative evaluation of morpholino-mediated protein knockdown of GFP, MSX1,
      and PAX7 during tail regeneration in Ambystoma mexicanum.
AB  - Vertebrate regeneration is a fascinating but poorly understood biological
      phenomena. Urodele amphibians such as Ambystoma mexicanum (the axolotl) can
      functionally regenerate complex body structures such as the limb and tail,
      including the spinal cord, throughout life. So far, molecular studies on
      regeneration have been limited due to the paucity of tools for knocking-down gene
      and protein function. In this article, we quantitatively assessed the ability of
      morpholinos to specifically down-regulate protein expression in both cultured
      urodele cells and in vivo. We focused on the down-regulation of green fluorescent
      protein and two axolotl proteins, MSX1 and PAX7. Our data show that the
      expression of these proteins can be efficiently reduced by morpholinos. MSX1 has
      been hypothesized to be involved in muscle dedifferentiation based on experiments
      using cultured myotubes. Our studies in in vivo muscle fibers so far have shown
      no influence of overexpressing or down-regulating MSX1 on the dedifferentiation
      process.

PMID- 15580633
TI  - Genome-wide identification of female-enriched genes in zebrafish.
AB  - Characteristic differences in morphology, physiology, and behavior between a male
      and female are correlated to the differential selection of sex-dependent
      transcriptomes. By using a cDNA array carrying approximately 9,000 zebrafish
      unique genes, we identified a group of genes whose expression are enriched in the
      female fish. A subset of these genes have been confirmed and further grouped as
      egg-enriched genes, as both somatic- and egg-enriched genes or as somatic
      enriched genes by means of RNA gel blot hybridization. Most importantly, a
      significant proportion of these genes are either functionally unknown or are
      novel genes. Thus, future studies of this group of genes will help us greatly to
      understand more about sex-determination and sex-related physiology and behavior.
      In addition, comparison of zebrafish female-enriched genes with that in
      Drosophila, we found that only germline genes are shared between vertebrate and
      invertebrate, suggesting that the process of oogenesis is highly conserved during
      the evolution.

PMID- 15580634
TI  - Supernumerary ring chromosome 7 mosaicism: case report, investigation of the gene
      content, and delineation of the phenotype.
AB  - We report a girl with severe retardation of expressive speech development
      carrying a small, supernumerary ring chromosome derived from the proximal region
      of the long arm of chromosome 7. The r(7) chromosome is present in 50% of
      lymphocytes. We also review the six additional cases with a supernumerary r(7)
      chromosome reported in the literature. Among these patients, a severe retardation
      of productive language capabilities is seen as a shared clinical feature,
      irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in
      these patients are minor and no shared congenital abnormalities seen. We,
      therefore, recommend chromosomal investigations in children with unexplained,
      disproportionately retarded expressive speech performance. Because speech and
      language acquisition are subject to genetic influences, we investigated whether
      there are genes on the r(7) chromosome that may affect brain development or
      function in a dosage-dependent manner. We found that both in our patient and in
      four patients described by others, the supernumerary r(7) chromosome contains the
      region from the centromere up to marker D7S613 located at 7q11.23. We speculate
      that the effects on speech acquisition are mediated by the supernumerary copies
      of the STX1A and LIMK1 genes, which are both located in this region and known to
      suppress neurite growth when overexpressed in vitro.

PMID- 15580635
TI  - Characterization of liver involvement in defects of cholesterol biosynthesis:
      long-term follow-up and review.
AB  - Inborn defects of cholesterol biosynthesis are a group of metabolic disorders
      presenting with mental retardation and multiple congenital anomalies (MCA/MR
      syndromes). Functional and structural liver involvement has been reported as a
      rare (2.5-6%) complication of the Smith-Lemli-Opitz syndrome (SLOS) and it has
      not been fully characterized. Here, we report on a long-term follow-up study of
      four patients with SLOS, and one case with lathosterolosis who presented with
      liver disease and underwent an extensive diagnostic work-up. Reports of liver
      involvement in cholesterol biosynthesis defects are reviewed. Two main different
      patterns of liver involvement emerged: progressive cholestasis, and stable
      isolated hypertransaminasemia. In our series, the first pattern was found in two
      patients with SLOS and one with lathosterolosis, and the second in two SLOS
      cases. Cholestasis was associated with early lethality and normal serum gamma
      glutamyl-transferase (GGT) levels in SLOS, while possible prolonged survival and
      high GGT levels were seen in lathosterolosis. Hepatic fibrosis was present in
      both conditions. Liver biopsy performed in one of our SLOS patients with isolated
      hypertransaminasemia, showed only mild hydropic degeneration of the hepatocytes.
      The presence of liver involvement in 16% of the SLOS patients diagnosed at our
      Center suggests that this complication might have been underestimated in
      previously reported cases, possibly overshadowed by the severity of multiple
      malformations. Fetal hepatopathy, cholestasis, and isolated hypertransaminasemia
      can occur also in other disorders of cholesterol biosynthesis, such as mevalonic
      aciduria, desmosterolosis, Conradi-Hunermann syndrome, Greenberg dysplasia, and
      Pelger-Huet homozygosity syndrome. This group of inherited disorders should be
      considered in the differential diagnosis of patients presenting with liver
      disease associated with developmental delay and/or multiple malformations.
      Periodic liver function evaluations are recommended in these patients.

PMID- 15580636
TI  - Fryns syndrome with Hirschsprung disease: support for possible neural crest
      involvement.
AB  - Fryns syndrome is an autosomal recessive multiple congenital anomaly/mental
      retardation syndrome characterized by coarse face, distal limb hypoplasia, and
      diaphragmatic anomalies. We describe a newborn girl with Fryns syndrome and
      Hirschsprung disease, an association that has been reported in five previous
      cases. These patients support the hypothesis that the neural crest plays a role
      in the pathogenesis of Fryns syndrome. Clinically asymptomatic or subtle
      anomalies that are in the spectrum of neural crest maldevelopment should be
      sought in all patients with Fryns syndrome including stillbirths, neonatal
      deaths, as well as long-term survivors. We suspect that the clinical observation
      about Hirschsprung disease and Fryns syndrome may provide insight into its
      molecular mechanisms and candidate genes.

PMID- 15580637
TI  - A patient with a ring chromosome 2 and microdeletion of 2q detected using FISH:
      Further support for "ring chromosome 2 syndrome".

PMID- 15580638
TI  - Maternal isodisomy of the telomeric end of chromosome 2 is responsible for a case
      of primary hyperoxaluria type 1.
AB  - Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of
      glyoxylate metabolism, in which excessive oxalates are formed by the liver and
      excreted by the kidneys, causing a wide spectrum of disease, ranging from renal
      failure in infancy to mere renal stones in late adulthood. This disease is caused
      by a deficiency of alanine:glyoxylate aminotransferase (AGT), which is encoded by
      a single copy gene, AGXT, located in 2q37.3. We identified an apparently
      homozygous, loss-of-function, mutation in a patient; the gene defect was present
      in the heterozygous mother but not in the patient's father. We performed a
      microsatellite repeat analysis using 13 specific chromosome 2 markers and non
      chromosome 2 minisatellites. Six specific chromosome 2 markers showed an
      apparently homozygous maternal inheritance while four showed a biparental
      transmission consistent with paternity (confirmed by minisatellite analysis).
      Quantitative PCR of AGXT exons 1 and 3 on the patient's and parents genomic DNA
      revealed the presence of two copies of the gene. This is the first case of PH1
      caused by segmental maternal isodisomy of 2q37.3.

PMID- 15580639
TI  - Towards improved clinical characterization of Leber congenital amaurosis:
      neurological and systemic findings.
AB  - Leber congenital amaurosis (LCA) is the most severe form of inherited retinal
      dystrophy that presents in infancy. LCA is both clinically and genetically
      heterogeneous. The aim of our study was to clarify the clinical aspects of LCA
      and to contribute to improved characterization of the disorder. We studied 40
      children affected by LCA (mean age at first observation: 19 months, range: 8-50
      months), who underwent a comprehensive evaluation that included:
      neurophthalmological evaluation, electroretinogram (ERG), and visual evoked
      potentials (VEPs), general and neurological examinations, developmental
      assessment using scales for visually impaired children, neuroradiological
      examinations, hepatic and renal function and metabolic investigations, brainstem
      auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known
      LCA genes are ongoing. The subjects are still being followed up at 6-/12-month
      intervals. All the subjects fulfilled De Laey's criteria for LCA. The
      neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without
      associated cerebellar signs). Cognitive development was normal in 24 cases,
      borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI
      were present in seven cases, and "molar tooth" sign in four; all the others had a
      normal neuroradiological picture. Among the subjects presenting with neurological
      signs, a subgroup (13 patients) emerged that was characterized by systemic (skin,
      kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity
      that can present as an isolated ocular manifestation, or in association with
      neurological and systemic abnormalities and support the need for a
      multidisciplinary approach to this entity and for genotype-phenotype studies.

PMID- 15580640
TI  - A clinical report of a patient with two abnormal cell lines: 46,XX,del(21)(q22.1)
      and 47,XX,+3.
AB  - Mosaicism for two chromosomally abnormal cell lines in the absence of a normal
      cell line is exceedingly rare. We report a patient with developmental and growth
      delay, mild dysmorphic features, a history of hypertension and hepatoblastoma who
      was found to be mosaic for two chromosomally abnormal cell lines. The cell lines,
      one containing a terminally deleted chromosome 21, the other trisomy 3, were
      found in her blood. Fibroblasts and hepatoblastoma tumor cells revealed only the
      presence of the deleted 21 cell line. Microsatellite marker analysis suggests a
      mosaic rather than chimeric etiology for the cell lines. This case is exceptional
      in that the presence of either of these two cell lines alone is uncommon; finding
      both of these cell lines in an individual appears to be unique.

PMID- 15580642
TI  - Developmental variability during early embryonic development of zebra fish, Danio
      rerio.
AB  - Early vertebrate embryos pass through a period of remarkable morphological
      similarity. Possible causes for such similarity of early embryos include
      modularity, developmental constraints, stabilizing selection, canalization, and
      exhausted genetic variability. Supposedly, each process creates different
      patterns of variation and covariation of embryonic traits. We study the patterns
      of variation of the embryonic phenotype to test ideas about possible evolutionary
      mechanisms shaping the early embryonic development. We use the zebra fish, Danio
      rerio, as a model organism and apply repeated measures of individual embryos to
      study temporal changes of phenotypic variability during development. In
      particular, we are looking at the embryonic development from 12 hours post
      fertilization until 27 hours post fertilization. During this time period, the
      development of individual embryos is documented at hourly intervals. We measured
      maximum diameter of the eye, length of embryo, number of somites, inclination of
      somites, and the yolk size (as a maternal effect). The coefficient of variation
      (CV) was used as a measure of variability that was independent of size. We used a
      principal component analysis for analysis of morphological integration. The
      experimental setup kept environment x genotype interactions constant. Nongenetic
      parental contributions had no significant effects on interindividual variability.
      Thus all observed phenotypic variation was based on additive genetic variance and
      error variance. The average CV declined from 14% to 7.7%. The decline of the CV
      was in particular expressed during 15-19 h post fertilization and occurred in
      association with multiple correlations among embryonic traits and a relatively
      high degree of morphological integration. We suggest that internal constraints
      determine the patterns of variability during early embryonic development of zebra
      fish.

PMID- 15580643
TI  - Developmental fate of the mandibular mesoderm in the lamprey, Lethenteron
      japonicum: Comparative morphology and development of the gnathostome jaw with
      special reference to the nature of the trabecula cranii.
AB  - The vertebrate jaw is a mandibular-arch derivative, and is regarded as the
      synapomorphy that defines the gnathostomes. Previous studies (Kuratani et al.,
      Phil. Trans. Roy. Soc. 356:15, 2001; Shigetani et al., Science 296:1319, 2002)
      have suggested that the oral apparatus of the lamprey is derived from both the
      mandibular and premandibular regions, and that the jaw has arisen as a secondary
      narrowing of the oral patterning mechanism into the mandibular-arch domain. The
      heterotopy theory of jaw evolution states that the lamprey upper lip is a
      premandibular element, leaving further questions unanswered as to the homology of
      the trabecula in the lamprey and gnathostomes, and to the morphological nature of
      the muscles in the upper lip. Using focal injection of vital dyes into the cheek
      process core of lamprey embryos, we found that the upper lip muscle and trabecula
      are both derived from mandibular mesoderm. Secondary movement of the muscle
      primordium is also evident when the expression of the early muscle marker gene,
      LjMA2, is visualized. A nerve-fiber labeling study revealed that the upper lip
      muscle-innervating neurons are located in the rostral part of the brain stem,
      where the trigeminal motor nuclei are not found in gnathostomes. We conclude that
      the lamprey upper lip is composed of premandibular ectomesenchyme and a lamprey
      specific muscle component derived from the mandibular mesoderm innervated by
      lamprey-specific motoneurons. Furthermore, the lamprey trabecula is most likely
      equivalent to a mesodermally derived neurocranial element, similar to the
      parachordal element in gnathostomes, rather than to the neural-crest-derived
      prechordal element.

PMID- 15580644
TI  - An unprecedented bridging phenoxyl radical in dicopper(II) complexes: evidence
      for an s=3/2 spin state.

PMID- 15580645
TI  - Metallophilicity versus pi-pi interactions: ligand-unsupported
      argentophilicity/cuprophilicity in oligomers-of-dimers [M2L2]n (M=CuI or AgI,
      L=tridentate ligand).
AB  - To verify whether attractive metallophilic interactions exist in the dimer-of
      dimers [Cu(2)(ophen)(2)](2) (Hophen=1H-[1,10]phenanthrolin-2-one) (1), we
      designed and synthesized a series of such [M(2)L(2)](2) structures by varying the
      d(10) metal and/or the ligand (M=Cu(I) or Ag(I), L=ophen or obpy; Hobpy=1H
      [2,2']bipyridinyl-6-one), and have successfully obtained three dimers-of-dimers:
      [Ag(2)(ophen)(2)](2).6 H(2)O (2), [Cu(2)(obpy)(2)](2) (3), and
      [Ag(2)(obpy)(2)](2).4.5 H(2)O.0.5 DMF (4). X-ray analyses of these structures
      show that interdimer M-M separations in [Ag(2)-(ophen)(2)](2) (3.199 A) are
      remarkably shorter than those in [Cu(2)(ophen)(2)](2) (3.595 A). Shorter
      interdimer M-M separations are found in the structures of [M(2)(obpy)(2)](2)
      (2.986 and 2.993 A in [Cu(2)(obpy)(2)](2), 3.037 to 3.093 A in
      [Ag(2)(obpy)(2)](2)), in which the pi systems are smaller than in the complexes
      with the ophen ligand. Detailed structural comparison of these dimers-of-dimers
      indicates that the interdimer, face-to-face pi-pi interactions repulse rather
      than support the interdimer metal-metal attractive interactions. This study also
      yields qualitative comparison of the strengths between argentophilic,
      cuprophilic, and face-to-face pi-pi interactions. DFT calculations on the four
      dimers-of-dimers further support the above deduction. The structure of a trimer
      of-dimers [Ag(2)(obpy)(2)](3) (Ag-Ag 3.171 to 3.274 A) is further evidence that
      the oligomerization of the [M(2)L(2)] molecules is favored by stronger
      metallophilic and weaker face-to-face pi-pi interactions.

PMID- 15580646
TI  - Efficient synthesis of thioesters and amides from aldehydes by using an
      intermolecular radical reaction in water.
AB  - The combination of the water-soluble radical initiator, 2,2'-azobis[2-(2
      imidazolin-2-yl)propane] dihydrochloride (VA-044) and the surfactant,
      cetyltrimethyl-ammonium bromide (CTAB), was found to be the most suitable
      condition for the effective and direct synthesis of useful active thioesters
      (pentafluorophenyl thioesters) in water. In addition, the direct amidation of
      aldehydes was achieved by the addition of the amines to the thioesterification
      reaction mixture in water.

PMID- 15580647
TI  - C5H4-BR2 bending in ferrocenylboranes: a delocalized through-space interaction
      between iron and boron.
AB  - A comparison of the molecular structures of mono-, di- and tetraborylated
      ferrocenes [Fc{B(R(1))(R(2))}] (R(1)/R(2)=Br/Br, Br/Fc, Br/Me, Me/Me, Me/OH,
      OMe/OMe), 1,1'-[fc{B(R(1))(R(2))}(2)] (R(1)/R(2)=Br/Br, Br/Me, OMe/OMe), and
      1,1',3,3'-[Fe{C(5)H(3)(BMe(2))(2)}(2)] revealed the boryl substituent(s) to be
      bent out of the Cp ring plane towards the iron center. The corresponding dip
      angle alpha* decreases with decreasing Lewis acidity of the boron atom and with
      increasing degree of borylation at the ferrocene core. This trend is well
      reproduced by DFT calculations (including [FcBH(2)], not yet accessible
      experimentally). A Bader analysis of the electron density topology of [FcBH(2)]
      (alpha*=26.5 degrees ; BP86/TZVP) clearly showed that there is no direct iron
      boron bonding in this compound. Instead, strongly delocalized orbital
      interactions have been identified that involve the boron p orbital, C(ipso) of
      the adjacent Cp ring, d orbitals at iron, and a through-space interaction with
      the second Cp ring. A second important factor is attractive electrostatic
      interactions, which are enhanced upon ligand bending. Cyclic voltammetric
      measurements on the series [FcBMe(2)], 1,1'-[fc(BMe(2))(2)], and 1,1',3,3'
      [Fe{C(5)H(3)(BMe(2))(2)}(2)] indicate a substantial anodic shift in the oxidation
      potential of the central iron atom upon introduction of BMe(2) substituents.
      Addition of 4-dimethylaminopyridine (DMAP) does not just counterbalance this
      effect, but leads to a cathodic shift of the Fe(II)/Fe(III) redox transition far
      beyond the half-wave potential of parent ferrocene. In the Mossbauer spectra, a
      continuous decrease in the quadrupole splitting (QS) is observed upon going from
      parent ferrocene to [FcBMe(2)], to 1,1'-[fc(BMe(2))(2)], and to 1,1',3,3'
      [Fe{C(5)H(3)(BMe(2))(2)}(2)]. In contrast, no significant differences are found
      between the QS values of ferrocene, [Fc(BMe(2)-DMAP)], and 1,1'-[fc(BMe(2)
      DMAP)(2)].

PMID- 15580648
TI  - Expanding the world of endohedral fullerenes--the Tm3N@C2n (39< or =n< or =43)
      clusterfullerene family.
AB  - A new family of endohedral fullerenes, based on an encaged trithulium nitride
      (Tm(3)N) cluster, was synthesised, isolated and characterised by HPLC, mass
      spectrometry, and visible-NIR and FTIR spectroscopy. Tm(3)N clusterfullerenes
      with cages as small as C(76) and as large as C(88) were prepared and six of them
      were isolated. Tm(3)N@C(78) is a small clusterfullerene. The two isomers of
      Tm(3)N@C(80) (I and II) were the most abundant structures in the fullerene soot.
      Tm(3)N@C(82), Tm(3)N@C(84), and Tm(3)N@C(86) represent a new series of higher
      clusterfullerenes. All six isolated Tm(3)N clusterfullerenes were classified as
      large energy-gap structures with optical energy gaps between approximately 1.2
      and approximately 1.75 eV. Tm(3)N@C(80) (I) and Tm(3)N@C(80) (II) were assigned
      to the C(80) cages C(80):7 (I(h)) and C(80):6 (D(5h)). For Tm(3)N@C(78), the
      analysis pointed to an elliptical carbon cage with C(78):1 (D(3)) or C(78):4
      (D(3h)) being the probable structures.

PMID- 15580649
TI  - In vivo administration of the C16:0 fatty acid isoform of sulfatide increases
      pancreatic sulfatide and enhances glucose-stimulated insulin secretion in Zucker
      fatty (fa/fa) rats.
AB  - BACKGROUND: Sulfatide is present in the secretory granules of beta cells and has
      been shown, in vitro, to be involved in insulin processing and secretion. Of
      particular interest is one of the major sulfatide isoforms in the beta cells, the
      C16:0 fatty acid isoform, which has been shown to be involved in insulin crystal
      preservation in vitro. The aim of this study was to investigate the ability of
      C16:0 fatty acid isoform of sulfatide to affect insulin secretion and/or action
      and glycaemic control in the adipogenic 'prediabetic' Zucker rat. METHODS: The
      C16:0 sulfatide was administered to Zucker rats for 10 weeks, and fasting levels
      of plasma insulin and glucose were measured as well as levels after an
      intravenous (i.v.) glucose load. In addition, the sulfatide expression, examined
      by thin-layer chromatography-enzyme-linked immunosorbent assay and mass
      spectrometry, in the pancreas of C16:0 sulfatide-treated Zucker rats was compared
      to controls. RESULTS: The in vivo treatment of Zucker rats with C16:0 sulfatide
      resulted in significantly elevated glucose-stimulated insulin secretion (60-80%
      increase, p < 0.05), without significant changes in glucose tolerance. The
      treatment was associated with an ameliorated first-phase insulin response (3-4
      fold, p = 0.009, 0.016) and a 60% increase of pancreatic sulfatide content (p =
      0.001), possible by an uptake of C16:0 sulfatide. The fasting hyperinsulinaemia
      and blood glucose levels were unchanged. CONCLUSIONS: The treatment with C16:0
      sulfatide elevates glucose-stimulated insulin secretion and enhances sulfatide
      content in the pancreas of Zucker rats.

PMID- 15580651
TI  - One-pot synthesis of sialo-containing glycosyl amino acids by use of an N
      trichloroethoxycarbonyl-beta-thiophenyl sialoside.
AB  - We describe an efficient synthesis of 2,6- and 2,3-sialyl T antigens linked to
      serine in a one-pot glycosylation. We first investigated the glycosidation of
      thiosialosides by varying the N-protecting group. Modification of the C-5 amino
      group of beta-thiosialosides into the N-9-fluorenylmethoxycarbonyl, N-2,2,2
      trichloroethoxycarbonyl (N-Troc), and N-trichloroacetyl derivatives enhanced the
      reactivity of these compounds towards glycosidation. Addition of a minimum amount
      of 3 A molecular sieves was also effective in improving the yield of alpha-linked
      sialosides. Next, we conducted one-pot syntheses of the glycosyl amino acids by
      using the N-Troc sialyl donor. The N-Troc derivative can be converted into the N
      acetyl derivative without racemization of the amino acids. Branched-type one-pot
      glycosylation, initiated by regioselective glycosylation of the 3,6-dihydroxy
      galactoside with the N-Troc-beta-thiophenyl sialoside, provided the protected 2,6
      sialyl T antigen in good yield. Linear-type one-pot glycosylation, initiated by
      chemoselective glycosylation of galactosyl fluoride with the N-Troc-beta
      thiophenyl sialoside, afforded the protected 2,3-sialyl T antigen in excellent
      yield. Both protected glycosyl amino acids were converted into the fully
      deprotected 2,6- and 2,3-sialyl T antigens linked to serine in good yields.

PMID- 15580650
TI  - Endothelin-mediated remodeling in aortas of diabetic rats.
AB  - BACKGROUND: Smooth muscle cells proliferation and extracellular matrix (ECM)
      protein deposition are key features of diabetic macroangiopathy. In the present
      study, we have studied the role of endothelin(A) (ET(A)) receptor, the
      predominant receptor on smooth muscle cells, in diabetes-induced vascular
      hypertrophy and remodeling. METHODS: Streptozotocin-induced diabetic rats were
      administrated a selective ET(A) receptor antagonist, TBC3214, for 26 weeks.
      Following treatment, aortas were harvested and subjected to gene expression and
      morphometric analyses. We quantified fibronectin (FN) and plasminogen activator
      inhibitor-1 (PAI-1) expression as indicators of increased ECM protein synthesis.
      ET-1, ET-3, transforming growth factor-beta1 (TGF-beta1) and angiotensinogen mRNA
      levels were measured to elucidate genes involved in FN expression. We have
      investigated an embryonic splice variant of FN, oncofetal FN, and nonmuscle
      myosin heavy chain (SMemb) as vascular remodeling indicators. RESULTS: Our
      results show that diabetes leads to upregulation of FN, PAI-1, ET-1, ET-3, TGF
      beta1 and angiotensinogen mRNA levels in association with increased medial
      thickness. Immunohistochemical analyses revealed concurrent protein level
      changes. Diabetes also upregulated oncofetal FN and SMemb mRNA levels. Treatment
      with TBC3214 attenuated the mRNA levels of several genes and prevented increased
      medial thickness. CONCLUSIONS: These results indicate that diabetes-induced
      vascular hypertrophy and remodeling is associated with reexpression of embryonic
      forms of FN and myosin heavy chain. Such changes are ET-dependent and may be
      mediated via TGF-beta1 and angiotensin.

PMID- 15580652
TI  - A density functional study on a biomimetic non-heme iron catalyst: insights into
      alkane hydroxylation by a formally HO-FeV=O oxidant.
AB  - The reactivity of [HO-(tpa)Fe(V)=O] (TPA=tris(2-pyridylmethyl)amine), derived
      from O-O bond heterolysis of its [H(2)O-(tpa)Fe(III)-OOH] precursor, was explored
      by means of hybrid density functional theory. The mechanism for alkane
      hydroxylation by the high-valent iron-oxo species invoked as an intermediate in
      Fe(tpa)/H(2)O(2) catalysis was investigated. Hydroxylation of methane and propane
      by HO-Fe(V)=O was studied by following the rebound mechanism associated with the
      heme center of cytochrome P450, and it is demonstrated that this species is
      capable of stereospecific alkane hydroxylation. The mechanism proposed for alkane
      hydroxylation by HO-Fe(V)=O accounts for the experimentally observed
      incorporation of solvent water into the products. An investigation of the
      possible hydroxylation of acetonitrile (i.e., the solvent used in the
      experiments) shows that the activation energy for hydrogen-atom abstraction by HO
      Fe(V)=O is rather high and, in fact, rather similar to that of methane, despite
      the similarity of the H-CH(2)CN bond strength to that of the secondary C-H bond
      in propane. This result indicates that the kinetics of hydrogen-atom abstraction
      are strongly affected by the cyano group and rationalizes the lack of
      experimental evidence for solvent hydroxylation in competition with that of
      substrates such as cyclohexane.

PMID- 15580653
TI  - CD8+ T cells from most HIV-1-infected patients, even when challenged with mature
      dendritic cells, lack functional recall memory to HIV gag but not other viruses.
AB  - Chronically HIV-1-infected patients fail to contain their viremia despite high
      frequencies of HIV-1-specific, IFN-gamma-producing CD8(+) T cells. However, these
      cells are known to exhibit both phenotypic and functional defects. We tested if
      mature dendritic cells (DC) could correct defective HIV-1 gag-specific T cell
      responses and if responses to other viral antigens were comparably affected. The
      circulating gag-specific CD8(+) T cells in fresh blood reliably produced IFN
      gamma but lacked IL-2 and high perforin levels and failed to expand significantly
      during culture with mature DC presenting HIV-1 gag peptides. In contrast, CD8(+)
      T cells from long-term nonprogressors contained gag-specific IFN-gamma and IL-2
      double producers, and the numbers of IFN-gamma producers expanded approximately
      15-fold during culture with DC. DC from chronically infected patients could
      expand IFN-gamma- and IL-2-producing cells specific for influenza,
      cytomegalovirus and Epstein Barr virus, and the expansions were comparable to
      those in healthy donors. When the proliferative capacity of CD8(+) T cells from
      progressor patients was assessed by CFSE dilution, proliferation to other viral
      antigens was more vigorous than to HIV-1 gag. Therefore, monocyte-derived DC from
      HIV patients present viral antigens effectively, but there is a selective
      inability to expand CD8(+) IFN-gamma-producing and IFN-gamma and IL-2 double
      producing T cells when challenged with HIV-1 gag.

PMID- 15580654
TI  - New insights into adenosine-receptor-mediated immunosuppression and the role of
      adenosine in causing the immunodeficiency associated with adenosine deaminase
      deficiency.
AB  - There is growing interest in manipulating adenosine (Ado) signal transduction to
      control inflammation and autoimmunity. This concept probably originated with the
      discovery of severe combined immunodeficiency disease (SCID) in infants with
      inherited deficiency of adenosine deaminase (ADA). However, the basis for
      immunosuppression by Ado has not been well defined, and effects of 2'
      deoxyadenosine (dAdo), which does not activate Ado receptors, have also been
      implicated in causing SCID. Here I discuss recent evidence that Ado, acting
      through its A2A receptor, interferes with NF-kappa B activation in antigen
      receptor-stimulated B and T lymphocytes. I also assess the relative contributions
      of Ado and dAdo to the pathogenesis of ADA-deficient SCID.

PMID- 15580655
TI  - The KIR gene family: life in the fast lane of evolution.
AB  - A hallmark of human NK cells is the expression of HLA class I-specific killer
      cell immunoglobulin-like receptors (KIR). An interesting facet of the KIR family
      is the unusual variability of the respective gene cluster, which is changing
      shape at an astonishing evolutionary pace. Not only do KIR genes come in
      different allelic variants, but the KIR locus has also gone through drastic
      contractions and expansions in recent evolutionary history, resulting in a wide
      variety of KIR haplotypes. A new study now reveals how an originally
      nonfunctional KIR pseudogene, KIR3DP1, is brought back to life in certain
      individuals via non-reciprocal recombination between two different KIR
      haplotypes. This Commentary outlines how the unique architecture of the KIR locus
      facilitates the generation of new KIR haplotypes and discusses the functional
      relevance of it.

PMID- 15580656
TI  - Adenosine and cAMP are potent inhibitors of the NF-kappa B pathway downstream of
      immunoreceptors.
AB  - Anergic B lymphocytes exert compromised signal transduction towards the
      activation of NF-kappa B in response to B cell antigen receptor (BCR) triggering,
      whereas activation of the ERK pathway appears normal. How this differential down
      regulation of the NF-kappa B pathway is regulated remains still elusive. Here, we
      demonstrate that stimuli known to enhance 3',5'-cyclic adenosine monophosphate
      (cAMP) are capable of selectively suppressing the activation both of NF-kappa B
      downstream of the BCR and Toll-like receptor 4 in splenic B lymphocytes and of
      the high-affinity receptor for IgE in BM-derived mast cells. This suppression is
      accomplished by blocking phosphorylation and subsequent degradation of the
      inhibitor of NF-kappa B. A cAMP-dependent protein kinase (PKA) inhibitor reverses
      this suppressive effect, indicating that PKA is a downstream effector of cAMP in
      this process. Importantly, not only drugs that artificially elevate intracellular
      cAMP levels, but also the nucleoside adenosine, which is known to be a mediator
      of cellular distress, inhibit the NF-kappa B pathway. This suggests that
      adenosine-mediated signals represent an important step in the molecular decision
      process controlling inflammation versus anergic immune responses.

PMID- 15580657
TI  - Transduction of naive CD4 T cells with kinase-deficient Lck-HIV-Tat fusion
      protein dampens T cell activation and provokes a switch to regulatory function.
AB  - We show here that T cell differentiation can be altered by exposing naive mouse
      CD4 T cells to altered T cell receptor signaling, achieved by transducing them
      with a fusion protein consisting of a modified Lck protein lacking the kinase
      domain and the HIV-Tat protein transduction domain. The Lck-HIV-Tat fusion
      protein is internalized into naive mouse T cells within 30 min after application
      to the medium. Activation of transduced cells in vitro resulted in strongly
      reduced intracellular calcium mobilization, alterations in cytokine profile, and
      sustained up-regulation of CD25. The cells had suppressive activity in vitro, but
      no Foxp3 expression. Our data indicate that signals encountered by a naive T cell
      during its initial activation can profoundly influence its subsequent functional
      behavior and elicit T cells, which can have regulatory activity.

PMID- 15580658
TI  - Cryptopatches and isolated lymphoid follicles: dynamic lymphoid tissues
      dispensable for the generation of intraepithelial lymphocytes.
AB  - In comparison to secondary lymphoid organs, gut-associated lymphoid tissues such
      as isolated lymphoid follicles (ILF) and cryptopatches (CP) have been less
      intensively studied. To gain a better insight into processes regulating
      organization and function of these structures, which are believed to participate
      in immune responses and extrathymic T cell development, we characterized the
      lymphoid structures of the murine small intestine in more detail. The size and
      cellular composition of small intestinal lymphoid aggregations were analyzed in
      C57BL/6 and BALB/c wild-type and lymphotoxin (LT)-deficient mice, by flow
      cytometry, histology and automated multi-color immunofluorescence microscopy
      evaluating large coherent areas of the intestine. These evaluations demonstrate
      that aggregated lymphoid structures in the small intestine vary in size and
      cellular composition, with a majority of structures not matching the current
      definitions of CP or ILF. Accordingly, significant variations depending on
      species, age and mouse strain were observed. Furthermore, small bowel
      transplantation revealed a rapid exchange of B but not T cells between host and
      grafted tissue. Moreover, LT-deficient animals lack any intestinal lymphoid
      aggregations yet possess the complete panel of intraepithelial lymphocytes (IEL).
      In summary, our observations disclose intestinal lymphoid aggregations as dynamic
      structures with a great deal of inborn plasticity and demonstrate their
      dispensability for the generation of IEL.

PMID- 15580659
TI  - The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted
      receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and
      KIR3DL1/KIR3DS1 genes are duplicated.
AB  - Killer-cell Ig-like receptors (KIR) are structurally and functionally diverse,
      and enable human NK cells to survey the expression of individual HLA class I
      molecules, often altered in infections and tumors. Multiple events of non
      reciprocal recombination have contributed to the rapid diversification of KIR. We
      show that approximately 4.5% of the individuals of a Caucasoid population bear a
      recombinant allele of KIR3DP1, officially designed KIR3DP1*004, that associates
      tightly with gene duplications of KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1. The
      KIR3DP1 gene is normally silent, but the recombinant allele carries a novel
      promoter sequence and, as a consequence, is transcribed in all tested
      individuals. Messenger RNA of KIR3DP1*004 is made up of six exons; of these,
      exons 1-5 are similar to, and spliced like, those encoding the leader peptide and
      Ig-domains of KIR3D. By contrast, exon 6 is homologous to no other human KIR
      sequence, but only to possible homologs in chimpanzees and rhesus macaques, and
      encodes a short hydrophilic tail. The putative KIR3DP1*004 product, like those of
      the related genes LAIR-2 and LILRA3/ILT6/LIR4, is predicted to be secreted to the
      extracellular medium rather than anchored to the cell membrane.

PMID- 15580660
TI  - Chemistry and biology of vitamin E.
AB  - Our understanding of the role of vitamin E in human nutrition, health, and
      disease has broadened and changed over the past two decades. Viewed initially as
      nature's most potent lipid-soluble antioxidant (and discovered for its crucial
      role in mammalian reproduction) we have now come to realize that vitamin E action
      has many more facets, depending on the physiological context. Although mainly
      acting as an antioxidant, vitamin E can also be a pro-oxidant; it can even have
      nonantioxidant functions: as a signaling molecule, as a regulator of gene
      expression, and, possibly, in the prevention of cancer and atherosclerosis. Since
      the term vitamin E encompasses a group of eight structurally related tocopherols
      and tocotrienols, individual isomers have different propensities with respect to
      these novel, nontraditional roles. The particular beneficial effects of the
      individual isomers have to be considered when dissecting the physiological impact
      of dietary vitamin E or supplements (mainly containing only the alpha-tocopherol
      isomer) in clinical trials. These considerations are also relevant for the design
      of transgenic crop plants with the goal of enhancing vitamin E content because an
      engineered biosynthetic pathway may be biased toward formation of one isomer. In
      contrast to the tremendous recent advances in knowledge of vitamin E chemistry
      and biology, there is little hard evidence from clinical and epidemiologic
      studies on the beneficial effects of supplementation with vitamin E beyond the
      essential requirement.

PMID- 15580661
TI  - Toll-like receptor 6-independent signaling by diacylated lipopeptides.
AB  - Bacterial lipopeptides are strong immune modulators that activate early host
      responses after infection as well as initiating adjuvant effects on the adaptive
      immune system. These lipopeptides induce signaling in cells of the immune system
      through Toll-like receptor 2 (TLR2)-TLR1 or TLR2-TLR6 heteromers. So far it has
      been thought that triacylated lipopeptides, such as the synthetic N-palmitoyl-S
      [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteine (Pam3)-CSK4, signal through
      TLR2-TLR1 heteromers, whereas diacylated lipopeptides, like the macrophage
      activating lipopeptide from Mycoplasma fermentans (MALP2) or S-[2,3
      bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteine (Pam2)-CGNNDESNISFKEK, induce
      signaling through TLR2-TLR6 heteromers. Using new synthetic lipopeptide
      derivatives we addressed the contribution of the lipid and, in particular, the
      peptide moieties with respect to TLR2 heteromer usage. In contrast to the current
      model of receptor usage, not only triacylated lipopeptides, but also diacylated
      lipopeptides like Pam2CSK4 and the elongated MALP2 analog Pam2CGNNDESNISFKEK-SK4
      (MALP2-SK4) induced B lymphocyte proliferation and TNF-alpha secretion in
      macrophages in a TLR6-independent manner as determined with cells from TLR6
      deficient mice. Our results indicate that both the lipid and the N-terminal
      peptides of lipoproteins contribute to the specificity of recognition by TLR2
      heteromers and are responsible for the ligand-receptor interaction on host cells.

PMID- 15580662
TI  - Exposure to nephrotoxic ochratoxin A enhances collagen secretion in human renal
      proximal tubular cells.
AB  - Ochratoxin A (OTA) is a nephrotoxic mycotoxin. There is evidence that OTA leads
      to cortical interstitial nephropathies in humans, associated with fibrosis. No
      data are available on the effect of OTA-induced collagen secretion from renal
      cortical cells. As kidney cortex mainly consists of proximal tubules, we
      investigated the effect of OTA on particular collagens (I, III, IV) in a well
      established proximal tubular cell line (opossum kidney (OK) cells) and in primary
      cultured human renal proximal tubular epithelial cells (RPTECs). In fibroblasts,
      OTA neither exerted toxic effects nor induced collagen secretion, most probably
      due to the absence of suitable uptake mechanisms. OTA exerted time- and dose
      dependent toxicity in both OK cells and human RPTECs. Moreover, OTA induced
      collagen secretion in a time- and dose-dependent manner in both cell types. In
      opposite to transforming growth factor beta1 (TGF-beta1), OTA incubation induced
      increased apical secretion of the basement membrane collagen IV. This might be
      evidence for a loss of cellular polarity after OTA incubation. We conclude that
      in proximal tubular cells, OTA is able to induce extracellular matrix deposition.
      As collagen secretion was also inducible in primary cultured human RPTECs, we
      hypothesize that OTA-induced extracellular matrix deposition by proximal tubular
      cells may be of importance in generation of renal diseases in humans which are
      under suspicion of being induced by OTA.

PMID- 15580663
TI  - Sensory evaluation of the synergism among odorants present in concentrations
      below their odor threshold in a Chinese jasmine green tea infusion.
AB  - The mechanism for the contribution of subthreshold aroma constituents to the
      overall jasmine tea odor impression was studied on the basis of a sensory
      evaluation. Binary model aqueous solutions containing the authentic odorants of a
      jasmine tea infusion, (E)-2-hexenyl hexanoate (I), (Z)-3-hexenol (II), and indole
      (III), were each prepared in a concentration below the odor threshold. Each
      solution had no aroma, but when 4-hexanolide replaced only 5% of each odorant,
      the odor intensity of each model solution was significantly strengthened. An
      astringent note and heavy note were recognized for each solution as the commonly
      perceived characteristics from the sensory evaluation. The concentration of 4
      hexanolide added was also at the subthreshold level. The results suggest mutual
      interaction between odorants I, II, or III and 4-hexanolide. The effect on the
      overall odor sensation of a jasmine tea infusion by adding 4-hexanolide at a
      concentration below its odor threshold was also studied. In this case, the
      intensity of both the sweet and astringent notes was significantly strengthened
      in comparison with the odor impression of the original jasmine tea infusion. This
      phenomenon is considered to have been a synergistic effect between subthreshold
      odor compounds in the jasmine tea infusion. The results of this study clarify for
      the first time that the subthreshold aroma constituents play an important role in
      the characteristic flavor of a jasmine tea infusion.

PMID- 15580664
TI  - Proceedings of a research meeting on anesthesia. June 19, 2004.

PMID- 15580666
TI  - Low-fat diet and a trio of lifestyle habits slash death rates.

PMID- 15580665
TI  - Revise your goals for heart health. Match your cholesterol profile and other data
      against new guidelines.

PMID- 15580667
TI  - U.S. heart attack patients outlive Canadian counterparts.

PMID- 15580668
TI  - FDA approves an over-the-counter home defibrillator.

PMID- 15580669
TI  - A warning about one statin at a high dose.

PMID- 15580670
TI  - Lessons from Clinton's bypass. Why the ex-President faced life-threatening
      arterial disease.

PMID- 15580671
TI  - Protecting the heart's "cradle". When painful symptoms can mislead patients and
      doctors.

PMID- 15580672
TI  - Overcoming the threat of anger. More than Type A behavior, hostility raises
      health risks.

PMID- 15580673
TI  - I was told that one of my heart arteries is completely blocked and that there is
      nothing doctors can do about it. Is this true?

PMID- 15580674
TI  - I've been taking aspirin daily for 25 years, and clopidogrel fro several years.
      In spite of this, I've had a number of heart attacks. You reported recently on
      people who can't benefit from aspirin, and I think I may be one of them. What
      should I do?

PMID- 15580675
TI  - My triglyceride level dropped from 76 in 2002 to 42 this year. During that
      period, I cut way back on consumption of sugary foods like cookies and candy. How
      much does this lower my risk of heart disease?

PMID- 15580676
TI  - Circulating epithelial cells in breast cancer.

PMID- 15580677
TI  - Hyperkalemia after the publication of RALES.

PMID- 15580678
TI  - Hyperkalemia after the publication of RALES.

PMID- 15580679
TI  - Hyperkalemia after the publication of RALES.

PMID- 15580680
TI  - Circulating epithelial cells in breast cancer.

PMID- 15580681
TI  - Circulating epithelial cells in breast cancer.

PMID- 15580682
TI  - Effects of diamond bur particle size on dentin bond strength.
AB  - PURPOSE: To evaluate the influence of particle size of originally designed
      diamond burs on resin adhesion to sound young human permanent dentin. METHODS:
      The buccal surfaces of 105 premolars were used. Six test groups were prepared.
      The adhesive systems and resin-based composites used for Groups 1-3 were Clearfil
      SE Bond (SE) and Clearfil AP-X, and for Groups 4-6, Single Bond (SB) and Z250.
      Flat dentin surfaces were finely ground with 25 microm particle size IW-G5
      diamond bur (IW-G5, Groups 1 and 4), 50 microm particle size IW-G4 diamond bur
      (IW-G4, Groups 2 and 5), or 600-grit SiC paper (#600, Groups 3 and 6). The
      microstructure of the prepared dentin, SE primed or SB etched dentin, and resin
      dentin interfaces of each group (3 teeth/group) were studied using SEM. Shear
      bond strengths (SBS) in MPa were tested (10 teeth/group), and the failed surfaces
      were observed using SEM. Data was statistically analyzed using ANOVA and Fisher's
      PLSD at P < 0.05. RESULTS: The dentin ground with the IW-G5 or IW-G4 bur was
      rougher than the dentin ground with the 600-grit SiC paper. The mean SBS (MPa)
      for Groups 1-6 were: 32.3 +/- 5.0, 27.6 +/- 6.4, 21.3 +/- 3.6, 5.9 +/- 2.9, 6.5
      +/- 3.1 and 5.3 +/- 2.0. The SBS of Groups 1-3 (SE groups) were significantly
      higher than those of Groups 4-6 (SB groups). The SBS of Group 1 (IW-G5, SE group)
      was significantly higher than those of Groups 2 (IW-G4, SE group) and 3 (#600, SE
      group), and the SBS of Group 2 was significantly higher than that of Group 3.
      There was no significant difference for SBS among Groups 4, 5 and 6. Fracture
      mode after SBS test mainly showed mixed fracture (adhesive and cohesive resin
      fracture) for the SE groups, and adhesive fracture for the SB groups.

PMID- 15580683
TI  - Synthesis and in vitro cytostatic activity of some new 1,3-(oxytetraethylenoxy)
      cyclotriphosphazatriene derivatives.
AB  - A series of cyclophosphazene crown ether derivatives bearing aziridinyl (ethylene
      imine) units and also 2-naphthyl or anthraquinone groups as co-substituents has
      been synthesized and their cytostatic activity against the panel of eight cancer
      cells in vitro has been studied. The substituents used exhibit different
      activities: alkylation (aziridinyl groups) and intercalation (naphtyl,
      anthraquinone groups) against DNA. These both interactions are supposed to
      enhance the efficiency of the cyclophosphazene crown ether derivatives studied as
      cytotoxic agents.

PMID- 15580684
TI  - Effect of dissolved oxygen on immune parameters of the white shrimp Litopenaeus
      vannamei.

PMID- 15580685
TI  - Re: supramalleolar osteotomy for the treatment of distal tibial angular
      deformities and arthritis of the ankle joint.

PMID- 15580686
TI  - Fourth International Workshop on Haploidentical Transplants, Naples, Italy, July
      8-10, 2004.
AB  - Many patients with high-risk hematological malignancies or with incurable inborn
      errors do not have an HLA-matched sibling and cannot find an HLA-matched donor
      for an allogeneic hematopoietic stem cell transplantation (SCT). Transplantation
      strategies using mismatched haploidentical family donors have been an important
      development. Although the procedure has saved patients from certain death, it is
      still beset by major problems like life-threatening infections--due to profound
      immunodeficiency following T-cell depletion and to disease relapse. At every
      International Workshop on Haploidentical Transplants, new data are presented,
      showing how scientists are attempting to improve the outcomes of mismatched
      transplants while reducing the severity of complications.The fourth Workshop
      continues in this tradition of presenting ground-breaking research. It opened
      with presentations of the current results with unrelated volunteer and umbilical
      cord blood transplants and proceeded to a session with the results of
      haploidentical transplants in the world with series of patients with high-risk
      acute leukemia, ranging in number from well over 100 in Perugia, Italy, and 80 in
      Haifa, Israel, to smaller groups in Europe and the United States. The session on
      graft engineering presented the latest results in the search for the optimal
      graft. The graft-vs.-leukemia effect in the haploidentical transplant was
      discussed in depth. Subsequently, attention focussed on one of the major problems
      in haploidentical transplant, that is, the delay in immunological recovery. The
      Workshop closed with presentations on tolerance induction that was followed by
      the results of ongoing registration studies being performed by the Italian GIMEMA
      group and the European Bone Marrow Transplant group.

PMID- 15580687
TI  - Enhancing autonomy and choice in selecting and directing long term care services.

PMID- 15580688
TI  - Case 24-2004: recurrent gastrointestinal bleeding in a 48-year-old man.

PMID- 15580689
TI  - Renaissance phage.

PMID- 15580690
TI  - Genomic pot pourri.

PMID- 15580691
TI  - Tuberculosis.

PMID- 15580692
TI  - Medical education and hard science.

PMID- 15580693
TI  - Most uninsured people unaware of health care safety net providers.
AB  - Less than half of uninsured Americans either typically use or are aware of a
      safety net provider in their community, according to a national study by the
      Center for Studying Health System Change (HSC). Among all uninsured people, those
      with lower-incomes, racial/ethnic minorities and people living closer to safety
      net providers are more likely to know of or use a safety net provider for medical
      care. Uninsured people identify physician offices and community health centers
      most frequently as sources of lower-cost medical care, while hospital-based
      facilities--outpatient and emergency departments--are less likely to be
      mentioned. Despite high levels of emergency department (ED) use by uninsured
      people, few identify EDs as places to get affordable medical care.

PMID- 15580694
TI  - Retraction of "Nuclear factor kappa B (NFkappaB) dependent modulation of Epstein
      Barr virus latent membrane protein 1 (LMP1) in epidermal growth factor receptor
      (EGFR) promotor activity" [Virus Research 104 (2004) 61-70].

PMID- 15580695
TI  - Paying for performance--the business case.

PMID- 15580696
TI  - Bill seeking to ban DNA discrimination isn't really necessary.

PMID- 15580697
TI  - Businesses are buying the ethics they want.

PMID- 15580698
TI  - [Proper use of antibiotics and related guidelines. Guidelines for the use of
      antibiotics and their outcome].

PMID- 15580699
TI  - [Kidney diseases--from diagnosis to transplantation. 1) Diagnosis].

PMID- 15580700
TI  - [Medical economics and quality of medical care: clinical path].

PMID- 15580701
TI  - From benign to malignant: who is watching the border?

PMID- 15580702
TI  - Toxicoproteomics: proteomics applied to toxicology and pathology.
AB  - Global measurement of proteins and their many attributes in tissues and biofluids
      defines the field of proteomics. Toxicoproteomics, as part of the larger field of
      toxicogenomics. seeks to identify critical proteins and pathways in biological
      systems that are affected by and respond to adverse chemical and environmental
      exposures using global protein expression technologies. Toxicoproteomics
      integrates 3 disciplinary areas: traditional toxicology and pathology,
      differential protein and gene expression analysis, and systems biology. Key
      topics to be reviewed are the evolution of proteomics, proteomic technology
      platforms and their capabilities with exemplary studies from biology and
      medicine, a review of over 50 recent studies applying proteomic analysis to
      toxicological research, and the recent development of databases designed to
      integrate -Omics technologies with toxicology and pathology. Proteomics is
      examined for its potential in discovery of new biomarkers and toxicity
      signatures, in mapping serum,plasma. and other biofluid proteomes, and in
      parallel proteomic and transcriptomic studies. The new field of toxicoproteomics
      is uniquely positioned toward an expanded understanding of protein expression
      during toxicity and environmental disease for the advancement of public health.

PMID- 15580703
TI  - Common vascular changes in the jugular vein of saline controls in continuous
      infusion in the beagle dog.
AB  - This review was performed to assess the nature and incidence of procedure-related
      background changes in control dogs receiving saline by continuous infusion, and
      to compare them with data from a similar review previously done in Cynomolgus
      monkeys. Data were collected from 14 dog studies performed over an 8-year period
      (i.e., 86 animals in total). The review was restricted to lesions at the
      injection site, in the lungs and at the catheter'sentry point. The most
      frequently seen changes were endothelial hyperplasia (67.4%) and intimal
      thickening at the injection site (80.2%) and interstitial pneumonitis in the
      lungs (52.6%), all seen at a higher incidence in dogs than in primates. Although
      incidences of thrombosis at the injection site were similar in both dogs (27.9%)
      and monkeys (34.1 %), the incidences of thromboemboli and secondary infarction in
      the lungs were much higher in dogs. This suggests that dogs have a greater
      propensity to thrombus formation and fragmentation at the injection site. However
      the fact that the femoral vein is used in monkeys and the jugular vein in dogs
      may explain this difference. The larger diameter of the jugular vein in the dog
      with its greater turbulence of blood flow possibly predisposes to fragmentation
      and dispersal of thrombi.

PMID- 15580704
TI  - Olfactory epithelial lesions induced by various cancer chemotherapeutic agents in
      mice.
AB  - In order to examine and compare the potential toxicity in the olfactory
      epithelium, the antitumor drug vincristine sulfate (VCR), vinblastine
      sulfate(VBL), vindesine sulfate (VDS), paclitaxel (PTX), mitomycin C (MMC), 5
      fluorouracil, (5-FU) or cisplatin (CDDP) was intravenously injected
      once(designated as day 1) at an estimated 10% lethal dose (LD(10)) to male BALB/c
      mice. The animals were necropsied on days 2, 5 and 15, and nasal tissues were
      examined by light-microscopy, counting of epithelial cells positive for terminal
      deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling
      (TUNEL), immunohistochemical staining with keratin antibody, and electron
      microscopy. Further, to delineate the drug disposition in the target organ, whole
      body radioluminography was performed 1 hour and 24 hours after treatment with the
      LD(10) of PTX or 5-FU. Of the antitumor drugs employed, only the antimicrotubule
      agents, VCR, VBL, VDS, and PTX, induced single cell death in the olfactory
      epithelium, especially sensory cells on day 2, atrophy of the olfactory
      epithelium on day 5, and myelin fragmentation in the trigeminal nerve on day 15.
      PTX induced the strongest changes among the 4 antimicrotubule agents. The cell
      death was confirmed to be apoptosis by TUNEL assay and electron microscopy,
      whereas the change in horizontal basal cells of the olfactory epithelium was
      shown not to be apoptosis by keratin staining. In quantitative
      radioluminography,radioactivity of PTX in the nasal tissues both 1 hour and 24
      hours after administration was about 4- or 5-fold higher than those of 5-FU.
      These results suggest that tubulin-targeting antitumour drugs could induce
      apoptosis in the olfactory epithelial cells of mice and that high drug
      distribution may effect the onset of the olfactory lesions.

PMID- 15580705
TI  - Progressive glomerulonephritis and histiocytic sarcoma associated with macrophage
      functional defects in CYP1B1-deficient mice.
AB  - The cytochrome P450 CYP1B1 enzyme metabolically activates polycyclic aromatic
      hydrocarbons and is a major P450 isoenzyme in human monocytes and macrophages. We
      have shown previously that mice deficient in CYP1B1 were resistant to induced
      tumors after 7,12-dimethylbenz[a]anthracene exposure. The pathology of aging
      CYP1B1 null mice on a B6; 129 background was studied in groups of 29 males and 30
      females. By 12 months, 50% of the female mice had developed a unusual progressive
      glomerulonephritis while males had similar renal lesions later in life. This
      disease followed a sequence of proliferative, membranoproliferative and sclerotic
      glomerulonephritis. Anti-DNA antibodies were found in the blood of the mice along
      with immune deposits containing immunoglobulins in subepithelial locations of the
      glomerular basement membrane. The lesions were unlike those found in aging wild
      type B6;129 mice or mice of other strains. We found that macrophages from CYP1B1
      null mice were impaired in the phagocytosis of apoptotic, necrotic, and opsonized
      cells. This suggests a generalized defect in the phagocytic activity of CYP1B1
      null mouse macrophages. Male mice also developed a high incidence (62-64%) of
      histiocytic sarcomas. Our study provides evidence that deficiency of CYP1B1 can
      play a role in the development of glomerular disease, normal processing of
      catabolic DNA and tumors of the mononuclear phagocyte system. The function of
      CYP1B1 in histiocytes and macrophages may involve both self-tolerance and tumor
      suppression.

PMID- 15580707
TI  - Current awareness of yeast.

PMID- 15580708
TI  - [Bioresonance, a study of pseudo-scientific language].

PMID- 15580706
TI  - Strain-specific of alachlor on murine olfactory mucosal responses.
AB  - Chloracetanilide herbicides are multisite carcinogens in rodents. Progression of
      alachlor-induced olfactory tumors in rats is accompanied by cytoplasmic
      accumulation and nuclear localization of beta-catenin, suggesting activation of
      Wint signaling. Female CD-1 mice were resistant to alachlor-induced olfactory
      carcinogenesis. The current studies were performed to determine whether
      Apc(Min/+) mice, which have activated Wnt signaling due to mutation of the second
      allele of Apc, would be susceptible to alachlor olfactory carcinogenesis. Female
      and male Apc(Min/+) mice, as well as Apc(+/+) littermates received alachlor in
      the diet (260 mg/kg/d) for up to 3 months. Female A/J and C57BL/6J wild-type mice
      were also treated (for 10 and 14 months, respectively), as these strains vary in
      sensitivity to many respiratory tract insults. No olfactory mucosal tumors were
      observed in any of the mice, although alachlor-treated Apc(Min/+) mice developed
      histological changes similar to those in alachlor-treated rats. Alachlor-treated
      A/J mice developed pronounced intracellular accumulation of amorphous
      eosinophilic material in the olfactory mucosa, foci of respiratory-like
      metaplasia,and hyperplasia of nasal mucus glands. A similar but less intense
      response was seen in C57BL/6J mice. Mice and rats had equivalent levels of the
      putative bioactivating enzyme (CYP2A) in olfactory mucosa. and mice had induced
      hepatic CYP3A and CYP2B enzymes with alachlor treatment, which may increase
      alachlor elimination. These studies extend previous observations by describing
      alachlor-induced olfactory mucosal changes in mice and suggest that hepatic
      metabolic enzyme induction may be responsible for resistance of mice to alachlor
      induced olfactory carcinogenesis.

PMID- 15580709
TI  - Accelerating the audit cycle: data gathering, analysis and dissemination of
      results by electronic methods. The third Yorkshire audit of genital chlamydial
      management.
AB  - An electronic database was used as an audit tool by a peripatetic audit or to
      collect data on the management of genital chlamydial infection from genitourinary
      medicine clinics. A paper proforma was used to obtain data on clinic facilities.
      The database generated pre-specified quantitative reports for comparison to
      national standards and guidelines, as well as comparison of performance between
      clinics and to a previous regional audit. Feedback and discussion took place to
      identify interventions intended to improve practice. This methodology allowed for
      rapid dissemination of the audit findings to clinics.

PMID- 15580711
TI  - Medicare for people with Alzheimer's disease.
AB  - This issue brief presents information about the types of services Medicare will
      cover for people with Alzheimer's disease.

PMID- 15580712
TI  - Do medical malpractice costs affect the delivery of health care?

PMID- 15580713
TI  - The effect of anti-fraud enforcement on Medicare costs and quality.

PMID- 15580714
TI  - Moonflower-induced anisocoria.

PMID- 15580715
TI  - Whole bowel irrigation and the capsule summary.

PMID- 15580716
TI  - A painful shoulder.

PMID- 15580717
TI  - Holes in the article on whole bowel irrigation.

PMID- 15580718
TI  - Another perspective on "Severe hypercapnia caused by acute heroin overdose".

PMID- 15580719
TI  - Individualised quality of life after pacing. Does mode matter?
AB  - AIMS: To examine the hypothesis that atrial based pacing improves Quality of Life
      (QoL) after pacing by undertaking a detailed QoL evaluation that includes an
      individualised assessment as well as disease specific evaluation. METHODS:
      Prospective study of patients randomised to VVI(R) or atrial based pacing modes
      using the Schedule for the Evaluation of Individual QoL (SEIQoL), the 36-item
      Medical Outcomes Study Short-Form General Health Survey (SF36), and a modified
      version of the Karolinska Cardiovascular Symptomatology Questionnaire (KCSQ).
      RESULTS: Seventy-three patients completed the two-year follow up of the study.
      Pacing improved SEIQoL scores, cardiovascular symptoms and the physical role
      limitation, social limitation and mental health domains of SF36 from baseline to
      one month. Pacing mode had no effect on QoL the major determinants of which were
      baseline QoL and a history of coronary artery disease. CONCLUSION: Atrial based
      pacing does not improve QoL in the two years after pacing when compared with
      VVI(R) pacing.

PMID- 15580720
TI  - The genesis of public health ethics.
AB  - As bioethics emerged in the 1960s and 1970s and began to have enormous impacts on
      the practice of medicine and research--fuelled, by broad socio-political changes
      that gave rise to the struggles of women, African Americans, gay men and
      lesbians, and the antiauthoritarianism impulse that characterised the New Left in
      democratic capitalist societies--little attention was given to the question of
      the ethics of public health. This was all the more striking since the core values
      and practices of public health, often entailing the subordination of the
      individual for the common good, seemed opposed to the ideological impulses of
      bioethics. Of what relevance is autonomy-focused bioethics for public health,
      with its mix of justifications including those that are either implicitly or
      explicitly paternalistic or that seek to impose strictures on individuals and
      communities in the name of collective welfare? To examine the deep divide between
      the central commitments of bioethics and the values that animate the practice of
      public health, we focus on a series of controversies implicating the concepts of
      privacy, liberty, and paternalism. Recognising the role of moral values in
      decision-making was a signal contribution of bioethics in its formative period.
      Over the past three decades a broad array of perspectives emerged under the
      rubric of bioethics but individualism remains central. As we commence the process
      of shaping an ethics of public health, it is clear that bioethics is the wrong
      place to start when thinking about the balances required in defence of the
      public's health.

PMID- 15580721
TI  - Toxic ethics: environmental genomics and the health of populations.
AB  - Dealing primarily with implications rather than foundations, and focusing
      downstream at the expense of upstream prevention, mainstream bioethics is at a
      toxic watershed. Through an extended analysis of the Environmental Genome Project
      (EGP), we offer new tools from the philosophy of science and from critical
      epidemiology to help bioethics to move ahead. Our aim in this paper is not to
      resolve the moral and conceptual problems we reveal, but rather to outline ways
      to prevent such problems from arising in future research.

PMID- 15580722
TI  - Vaccination and the prevention problem.
AB  - This paper seeks to critically review a traditional objection to preventive
      medicine (which I call here the 'prevention problem'). The prevention problem is
      a concern about the supposedly inequitable distribution of benefits and risks of
      harm resulting from preventive medicine's focus on population-based
      interventions. This objection is potentially applicable to preventive vaccination
      programmes and could be used to argue that such programmes are unethical. I
      explore the structure of the prevention problem by focusing upon two different
      types of vaccination (therapeutic vaccination and preventive vaccination). I
      argue that the 'prevention problem' cannot be fairly applied to the case of
      preventive vaccination because such programmes do not just focus upon benefits at
      the level of populations (as is claimed by the prevention problem). Most such
      preventive vaccination programmes explicitly seek to create and maintain herd
      protection. I argue that herd protection is an important public good which is a
      benefit shared by all individuals in the relevant population. This fact can then
      be used to block the 'prevention problem' argument in relation to preventive
      vaccination programmes. I conclude by suggesting that whilst the future
      development and use of therapeutic vaccines does raise some interesting ethical
      issues, any ethical objections to prophylactic vaccination on the basis of the
      'prevention problem' will not be overcome through the substitution of therapeutic
      vaccines for preventive vaccines; indeed, the 'prevention problem' fails on its
      own terms in relation to preventive vaccination programmes.

PMID- 15580723
TI  - Guilt, fear, stigma and knowledge gaps: ethical issues in public health
      communication interventions.
AB  - Public health communication campaigns have been credited with helping raise
      awareness of risk from chronic illness and new infectious diseases and with
      helping promote the adoption of recommended treatment regimens. Yet many aspects
      of public health communication interventions have escaped the scrutiny of ethical
      discussions. With the transference of successful commercial marketing
      communication tactics to the realm of public health, consideration of ethical
      issues becomes an essential component in the development and application of
      public health strategies. Ethical issues in public health communication are
      explored as they relate to eight topics: 'targeting' and 'tailoring' public
      health messages to particular population segments; obtaining the equivalence of
      informed consent; the use of persuasive communication tactics; messages on
      responsibility and culpability; messages that apply to harm reduction; and three
      types of unintended adverse effects associated with public health communication
      activities that may label and stigmatise, expand social gaps, and promote health
      as a value. We suggest that an ethical analysis should be applied to each phase
      of the public health communication process in order to identify ethical dilemmas
      that may appear subtle, yet reflect important concerns regarding potential
      effects of public health communication interventions on individuals and society
      as a whole.

PMID- 15580724
TI  - Correlates of parental participation during informed consent for randomized
      clinical trials in the treatment of childhood leukemia.
AB  - This study described parent participation in the informed consent conference for
      randomized clinical trials (RCTs) in childhood leukemia and documented the
      relationship of physician communication to parent participation. Parents of 140
      children with newly diagnosed leukemia who were eligible for RCTs were studied at
      six sites using comprehensive methods involving direct observation and
      transcripts of parent-physician communication based on audiotapes. Parent
      participation during the informed consent conference reflected a wide range of
      content categories. Consistent with hypotheses, Physician Rapport and Partnership
      Building related to parent participation in the informed consent conference but
      Information Giving did not. Higher parent socioeconomic status also was related
      to greater parent participation for two of the three measures of parent
      participation. Findings suggest that physician behaviors that provide support and
      facilitate communication may enhance parental participation in the informed
      consent conference for RCTs in childhood leukemia.

PMID- 15580725
TI  - Regulatory and ethical principles in research involving children and individuals
      with developmental disabilities.
AB  - Children and individuals with developmental disabilities (DD) compared to typical
      participants are disadvantaged not only by virtue of being vulnerable to risks
      inherent in research participation but also by the higher likelihood of exclusion
      from research altogether. Current regulatory and ethical guidelines although
      necessary for their protection do not sufficiently ensure fair distributive
      justice. Yet, in view of disproportionately higher burdens of co-occurring
      physical and mental disorders in individuals with DD, they are better positioned
      to benefit from research by equitable participation. Greater elucidation of this
      ethical dilemma is called for by researchers, institutional review boards, and
      funding agencies to urgently redress the imbalance. This article discusses many
      of the regulatory principles to ensure better research participation of children
      and individuals with DD: human rights, validity, distributive justice,
      beneficence/nonmaleficence, and autonomy.

PMID- 15580726
TI  - Adult immunization programs in nontraditional settings: quality standards and
      guidance for program evaluation.
AB  - This report provides a summary of the National Vaccine Advisory Committee's
      (NVAC) workshop on adult immunization programs in nontraditional settings,
      quality standards for such programs, and guidance for program evaluation.
      Throughout the United States, an increasing number of adults are receiving
      vaccine in nontraditional settings (e.g., pharmacies and churches). Immunization
      programs in nontraditional settings are often more accessible and convenient than
      a health-care provider's office or a public health clinic, especially for
      medically underserved adults (e.g., economically disadvantaged, inner city, and
      minority populations). Medically underserved adults might be at particular risk
      for undervaccination because they are often without a medical home (i.e., a
      regular point of contact where their health-care needs are met). Immunization
      programs in nontraditional settings might enhance the capacity of the health-care
      system to effectively deliver vaccine to adults by increasing the number and
      types of sites where adults can receive vaccine. NVAC has recognized that
      strategies need to be developed to make vaccines available to all adults and that
      the number of immunization programs in nontraditional settings is increasing.
      Therefore, the Committee issues the following report, including quality standards
      and guidance for program evaluation.

PMID- 15580727
TI  - Use of standing orders programs to increase adult vaccination rates.
AB  - The Advisory Committee on Immunization Practices recognizes the need for evidence
      based policy to improve the delivery and receipt of immunization services
      recommended for adults (i.e., persons aged > or = 18 years). Two recent,
      systematic reviews of the health services research literature recommended
      standing orders programs as an effective organizational intervention to improve
      vaccination coverage rates among adults. This report briefly reviews the evidence
      on the effectiveness of standing orders programs, describes standards for program
      implementation, and recommends initiating these programs to improve immunization
      coverage in several traditional and nontraditional settings.

PMID- 15580728
TI  - Poliomyelitis prevention in the United States. Updated recommendations of the
      Advisory Committee on Immunization Practices (ACIP).
AB  - These recommendations of the Advisory Committee on Immunization Practices (ACIP)
      for poliomyelitis prevention replace those issued in 1997. As of January 1, 2000,
      ACIP recommends exclusive use of inactivated poliovirus vaccine (IPV) for routine
      childhood polio vaccination in the United States. All children should receive
      four doses of IPV at ages 2, 4, and 6-18 months and 4-6 years. Oral poliovirus
      vaccine (OPV) should be used only in certain circumstances, which are detailed in
      these recommendations. Since 1979, the only indigenous cases of polio reported in
      the United States have been associated with the use of the live OPV. Until
      recently, the benefits of OPV use (i.e., intestinal immunity, secondary spread)
      outweighed the risk for vaccine-associated paralytic poliomyelitis (VAPP) (i.e.,
      one case among 2.4 million vaccine doses distributed). In 1997, to decrease the
      risk for VAPP but maintain the benefits of OPV, ACIP recommended replacing the
      all-OPV schedule with a sequential schedule of IPV followed by OPV. Since 1997,
      the global polio eradication initiative has progressed rapidly, and the
      likelihood of poliovirus importation into the United States has decreased
      substantially. In addition, the sequential schedule has been well accepted. No
      declines in childhood immunization coverage were observed, despite the need for
      additional injections. On the basis of these data, ACIP recommended on June 17,
      1999, an all-IPV schedule for routine childhood polio vaccination in the United
      States to eliminate the risk for VAPP. ACIP reaffirms its support for the global
      polio eradication initiative and the use of OPV as the only vaccine recommended
      to eradicate polio from the remaining countries where polio is endemic.

PMID- 15580729
TI  - Reducing falls and resulting hip fractures among older women.
AB  - SCOPE OF THE PROBLEM: Fall-related injuries are the leading cause of injury
      deaths and disabilities among older adults (i.e., persons aged > or = 65 years).
      The most serious fall injury is hip fracture; one half of all older adults
      hospitalized for hip fracture never regain their former level of function. In
      1996, a total of 340,000 hospitalizations for hip fracture occurred among persons
      aged > or = 65 years, and 80% of these admissions occurred among women. From 1988
      to 1996, hip fracture hospitalization rates for women aged > or = 65 years
      increased 23%. ETIOLOGIC OR RISK FACTORS: Risk factors for falls include
      increasing age, muscle weakness, functional limitations, environmental hazards,
      use of psychoactive medications, and a history of falls. Age is also a risk
      factor for hip fracture. Women aged > or = 85 years are nearly eight times more
      likely than women aged 65-74 years to be hospitalized for hip fracture. White
      women aged > or = 65 years are at higher risk for hip fracture than black women.
      Other riskfactors for hip fracture include lack of physical activity,
      osteoporosis, low body mass index, and a previous hip fracture. RECOMMENDATIONS
      FOR PREVENTION: Because approximately 95% of hip fractures result from falls,
      minimizing fall risk is a practical approach to reducing these serious injuries.
      Research demonstrates that effective fall prevention strategies require a
      multifaceted approach with both behavioral and environmental components.
      Important elements include education and skill building to increase knowledge
      about fall risk factors, exercise to improve strength and balance, home
      modifications to reduce fall hazards, and medication assessment to minimize side
      effects (e.g., dizziness and grogginess). PROGRAM AND RESEARCH NEEDS:
      Coordination needs to be improved among the diverse Federal, state, and local
      organizations that conduct fall prevention activities. The effectiveness of
      existing fall prevention programs among specific groups of women (e.g., those
      aged > or = 85 years or living with functional limitations) needs careful
      evaluation. New primary fall prevention approaches are needed (e.g.,
      characterizing footwear that promotes stability), as well as secondary prevention
      strategies (e.g., protective hip pads) that can prevent injuries when falls
      occur. Finally, efforts are needed to increase collaboration among national
      experts from various disciplines, to reach consensus regarding priority research
      areas and program issues, and to work toward long-term strategies for reducing
      falls and fall-related injuries among older adults. CONCLUSION: Persons aged > or
      = 65 years constitute the fastest-growing segment of the U.S. population. Without
      effective intervention strategies, the number of hip fractures will increase as
      the U.S. population ages. Fall prevention programs have reduced falls and fall
      related injuries among high-risk populations using multifaceted approaches that
      include education, exercise, environmental modifications, and medication review.
      These programs need to be evaluated among older adults aged > or = 65 years who
      are living independently in the community. In addition, secondary prevention
      strategies are needed to prevent hip fractures when falls occur. Effective public
      health strategies need to be implemented to promote behavioral changes, improve
      current interventions, and develop new fall prevention strategies to reduce
      future morbidity and mortality associated with hip fractures among older adults.

PMID- 15580730
TI  - Exercise-related injuries among women: strategies for prevention from civilian
      and military studies.
AB  - SCOPE OF THE PROBLEM: The numerous health benefits of physical activity have been
      well documented, resulting in public health support of regular physical activity
      and exercise. Although beneficial, exercise also has corresponding risks,
      including musculoskeletal injuries. The incidence and risk factors for exercise
      related injury have been poorly assessed in women. Many civilian exercise
      activities (e.g., jogging, walking, and erobics) have corollaries in military
      physical training; injury incidence and risk factors associated with military
      physical training have been more thoroughly studied. ETIOLOGIC FACTORS: Injury
      risks increase as the amount of training increases (increased xposure). The same
      exercise parameters that can be modified to enhance physical fitness (i.e.,
      frequency, duration, and intensity) also influence the risk for injury in a dose
      response manner. Higher levels of current physical fitness (aerobic fitness)
      protect the participant against future injury. A history of previous injury is a
      risk factor for future injury. Smoking cigarettes has been associated with
      increased risk for exercise-related injury. Studies conducted in military
      populations suggest that the most important risk factor for injuries among
      persons engaged in vigorous weight-bearing aerobic physical activity might be low
      aerobic fitness rather than female sex. RECOMMENDATIONS FOR PREVENTION: Because
      of the limited scientific research regarding women engaging in exercise, general
      recommendations are provided. Women starting exercise programs should be
      realistic about their goals and start slowly at frequency, duration, and
      intensity levels commensurate with their current physical fitness condition.
      Women should be informed about the early indicators of potential injury. Women
      who have sustained an injury should take precautions to prevent reinjury (e.g.,
      ensuring appropriate recovery and rehabilitation). RESEARCH AGENDA: In general, a
      combination of factors affects the risk for exercise-related injury in women. How
      these factors act singly and in combination to influence injury risk is not well
      understood. Additional research regarding exercise-related injury in women is
      needed to answer many of the remaining epidemiologic questions and to help
      develop exercise programs that improve health while reducing the risk for injury.
      CONCLUSION: Exercise is an important component in improving and maintaining
      health; however, injury is also an accompanying risk. A review of key military
      and civilian research studies regarding exercise-related injuries provides some
      clues to reducing these injuries in women. Greater adherence to exercise
      guidelines can help decrease these risks.

PMID- 15580731
TI  - Implementing recommendations for the early detection of breast and cervical
      cancer among low-income women.
AB  - SCOPE OF THE PROBLEM: Among U.S. women, breast cancer is the most commonly
      diagnosed cancer and remains second only to lung cancer as a cause of cancer
      related mortality. The American Cancer Society (ACS) estimates that 182,800 new
      cases of female breast cancer and 41,200 deaths from breast cancer will occur in
      2000. Since the 1950s, the incidence of invasive cervical cancer and mortality
      from this disease have decreased substantially; much of the decline is attributed
      to widespread use of the Papanicolaou (Pap) test. ACS estimates that 12,800 new
      cases of invasive cervical cancer will be diagnosed, and 4,600 deaths from this
      disease will occur in the United States in 2000. ETIOLOGIC FACTORS: The risk for
      breast cancer increases with advancing age; other risk factors include personal
      or family history of breast cancer, certain benign breast diseases, early age at
      menarche, late age at menopause, white race, nulliparity, and igher socioeconomic
      status. Risk factors for cervical cancer include certain human papilloma virus
      infections, early age at first intercourse, multiple male sex partners, a history
      of sexually transmitted diseases, and low socioeconomic status. Black, Hispanic,
      or American Indian racial/ethnic background is considered a risk factor because
      cervical cancer detection and death rates are higher among these women.
      RECOMMENDATIONS FOR PREVENTION: Because studies of the etiology of breast cancer
      have failed to identify feasible primary prevention strategies suitable for use
      in the general population, reducing mortality from breast cancer through early
      detection has become a high priority. The potential for reducing death rates from
      breast cancer is contingent on increasing mammography screening rates and
      subsequently detecting the disease at an early stage--when more treatment options
      are available and survival rates are higher. Effective control of cervical cancer
      depends primarily on early detection of precancerous lesions through use of the
      Papanicolaou test, followed by timely evaluation and treatment. Thus, the
      intended outcome of cervical cancer screening differs from that of breast cancer
      screening. In 1991, the National Breast and Cervical Cancer Early Detection
      Program (NBCCEDP) was implemented to increase breast and cervical cancer
      screening among uninsured, low-income women. RESEARCH AGENDA: To support
      recommended priority activities for NBCCEDP, CDC has developed a research agenda
      comprising six priorities. These six priorities are a) determining effective
      strategies to communicate changes in NBCCEDP policy to cancer screening providers
      and women enrolled in the program; b) identifying effective strategies to
      increase the proportion of enrolled women who complete routine breast and
      cervical cancer rescreening according to NBCCEDP policy; c) identifying effective
      strategies to increase NBCCEDP enrollment among eligible women who have never
      received breast or cervical cancerscreening; d) evaluating variations in clinical
      practice patterns among providers of NBCCEDP screening services; e) determining
      optimal models for providing case-management services to women in NBCCEDP who
      have an abnormal screening result, precancerous breast or cervical lesion, or a
      diagnosis of cancer; and f) conducting economic analyses to determine costs of
      providing screening services in NBCCEDP. CONCLUSION: The NBCCEDP, through
      federal, state, territorial, and tribal governments, in collaboration with
      national and community-based organizations, has increased access to breast and
      cervical cancer screening among low-income and uninsured women. This initiative
      enabled the United States to make substantial progress toward achieving the
      Healthy People 2000 objectives for breast and cervical cancer control among
      racial/ethnic minorities and persons who are medically underserved. A continuing
      challenge for the future is to increase national commitment to providing
      screening services for all eligible uninsured women to ultimately reduce
      morbidity and mortality from breast and cervical cancer.

PMID- 15580732
TI  - Preventing congenital toxoplasmosis.
AB  - SCOPE OF THE PROBLEM: Toxoplasmosis is caused by infection with the protozoan
      parasite Toxoplasma gondii. Acute infections in pregnant women can be transmitted
      to the fetus and cause severe illness (e.g., mental retardation, blindness, and
      epilepsy). An estimated 400-4,000 cases of congenital toxoplasmosis occur each
      year in the United States. Of the 750 deaths attributed to toxoplasmosis each
      year, 375 (50%) are believed to be caused by eating contaminated meat, making
      toxoplasmosis the third leading cause of foodborne deaths in this country.
      ETIOLOGIC FACTORS: Toxoplasma can be transmitted to humans by three principal
      routes: a) ingestion of raw or inadequately cooked infected meat; b) ingestion of
      oocysts, an environmentally resistant form of the organism that cats pass in
      their feces, with exposure of humans occurring through exposure to cat litter or
      soil (e.g., from gardening or unwashed fruits or vegetables); and c) a newly
      infected pregnant woman passing the infection to her unborn fetus.
      RECOMMENDATIONSFOR PREVENTION: Toxoplasma infection can be prevented in large
      part by a) cooking meat to a safe temperature (i.e., one sufficient to kill
      Toxoplasma); b) peeling or thoroughly washing fruits and vegetables before
      eating; c) cleaning cooking surfaces and utensils afterthey have contacted raw
      meat, poultry, seafood, or unwashed fruits or vegetables; d) pregnant women
      avoiding changing cat litter or, if no one else is available to change the cat
      litter, using gloves, then washing hands thoroughly; and e) not feeding raw or
      undercooked meat to cats and keeping cats inside to prevent acquisition of
      Toxoplasma by eating infected prey. RESEARCH AGENDA: Priorities for research were
      discussed at a national workshop sponsored by CDC in September 1998 and include
      a) improving estimates of the burden of toxoplasmosis, b) improving diagnostic
      tests to determine when a person becomes infected with Toxoplasma, and c)
      determining the applicability of national screening programs. CONCLUSION: Many
      cases of congenital toxoplasmosis can be prevented. Specific measures can be
      taken by women and their health-care providers to decrease the risk for infection
      during pregnancy and prevent severe illness in newborn infants.

PMID- 15580733
TI  - Prevention and control of influenza: recommendations of the Advisory Committee on
      Immunization Practices (ACIP).
AB  - This report updates 1999 recommendations by the Advisory Committee on
      Immunization Practices (ACIP) on the use of influenza vaccine and antiviral
      agents (MMWR 1999;48[No. RR-4]: 1-29). These recommendations include five
      principal changes: a) the age for universal vaccination has been lowered to 50
      years from 65 years; b) scheduling of large, organized vaccination campaigns
      after mid-October may be considered because the availability of vaccine in any
      location cannot be assured consistently in the early fall; c) 2000-2001 trivalent
      vaccine virus strains are A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99
      (H1N1)-like, and B/Beijing/184/93-like strains; d) information on neuraminidase
      inhibitor antiviral drugs has been added; and e) a list of other influenza
      related infection control documents for special populations has been added. This
      report and other information on influenza can be accessed at the website for the
      Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for
      Infectious Diseases, CDC at <http://www.
      cdc.gov/ncidod/diseases/flu/fluvirus.htm>.

PMID- 15580734
TI  - Using tandem mass spectrometry for metabolic disease screening among newborns. A
      report of a work group.
AB  - Increasingly, tandem mass spectrometry (MS/MS) is being used for newborn
      screening because this laboratory testing technology substantially increases the
      number of metabolic disorders that can be detected from dried blood-spot
      specimens. In June 2000, the National Newborn Screening and Genetics Resource
      Center, in collaboration with CDC and the Health Resources and Services
      Administration, convened a workshop in San Antonio, Texas. Workshop participants
      examined programmatic concerns for health providers choosing to integrate MS/MS
      technology into their newborn screening activities. Representatives from
      approximately 50 public and private health agencies and universities participated
      in the workshop. The workshop participants and work group focused on laboratory
      methodology, decision criteria, quality assurance, diagnostic protocols, patient
      case management, and program evaluation for using MS/MS to analyze dried blood
      spots routinely collected from newborns. This work group report contains
      proposals for planning, operating, and evaluating MS/MS technology in newborn
      screening and maternal and child health programs. As a supplement to these
      proposals, this report contains synopses of selected presentations made at the
      2000 workshop regarding integration of MS/MS technology into newborn screening
      programs. The proposals contained in this report should assist policymakers,
      program managers, and laboratorians in making informed decisions regarding the
      process of including MS/MS technology in their newborn screening and maternal and
      child health programs.

PMID- 15580735
TI  - Results of the surgical treatment of spondylolisthesis.

PMID- 15580736
TI  - Orthopaedic measures in the treatment of severe burns.

PMID- 15580737
TI  - Skeletal manifestations and treatment of Gaucher's disease. Review of twenty
      cases.

PMID- 15580738
TI  - Congenital metatarsus adductus: the results of treatment.

PMID- 15580739
TI  - Lumbar fracture-dislocation. A study of twenty-one cases.

PMID- 15580740
TI  - Treatment of unicameral bone cyst. A follow-up study of one hundred seventy-five
      cases.

PMID- 15580741
TI  - Dysplasia epiphysealis hemimelica. A report of fifteen cases and a review of the
      literature.

PMID- 15580742
TI  - Arthrodesis of the carpal bones in the treatment of Kienbock's disease, painful
      ununited fractures of the navicular and lunate bones with avascular necrosis, and
      old fracture-dislocations of carpal bones.

PMID- 15580743
TI  - Autogenous transplantation of an interphalangeal joint and proximal phalangeal
      epiphysis. Case report and ten-year follow-up.

PMID- 15580744
TI  - Giant-cell tumor of the thoracic spine with pathological fracture and
      paraparesis: a method of stabilization. A case report.

PMID- 15580745
TI  - Using Teflon in arthroplasty of the hip-joint.

PMID- 15580746
TI  - Who speaks for dentistry?

PMID- 15580747
TI  - Pathology case of the month (June).

PMID- 15580748
TI  - Overarching issues in the 2005 Texas legislature.

PMID- 15580749
TI  - The 2005 TDA Legislative agenda: a work in progress.

PMID- 15580750
TI  - Reloading for the next battle: DENPAC's statewide grassroots plan.

PMID- 15580751
TI  - TSBDE sets passing scores for new dental assistant exams.

PMID- 15580752
TI  - TDA works to resolve nursing home care problems.

PMID- 15580753
TI  - Rule changes approved by Texas State Board of Dental Examiners.

PMID- 15580754
TI  - Federal issues and trends affecting dentistry.

PMID- 15580755
TI  - ADPAC Washington update, summer 2004.

PMID- 15580756
TI  - Real man of genius: II.

PMID- 15580757
TI  - Dentists in rural areas of Texas.

PMID- 15580758
TI  - Texas community residential facilities for individuals with intellectual and
      developmental disabilities.

PMID- 15580759
TI  - Oral and maxillofacial pathology case of the month. Metastatic prostate carcinoma
      (osteoblastic metastasis).

PMID- 15580760
TI  - Action.

PMID- 15580761
TI  - Keeping patients happy in your waiting room.

PMID- 15580762
TI  - Cellular and molecular control of dendritic growth and development of cerebellar
      Purkinje cells.
AB  - Purkinje cells are the principal neurons of the cerebellar cortex and are
      characterized by a large and highly branched dendritic tree. For this reason,
      they have for a long time been an attractive model system to study the regulation
      of dendritic growth and differentiation. In this article, I will first review
      studies on different aspects of Purkinje cell dendritic development and then go
      on to present studies which have aimed at experimentally altering Purkinje cell
      dendritic development. Some of the cellular and molecular mechanisms which have
      been shown by these studies to be important determinants of Purkinje cell
      dendritic development will be discussed, in particular the role of the parallel
      fiber input, of hormones, and of neuronal growth factors. The organotypic slice
      culture method will be introduced as an important experimental tool to study
      Purkinje cell dendritic development under controlled conditions. Using cerebellar
      slice cultures, protein kinase C (PKC) has been identified as a major determinant
      of Purkinje cell dendritic development and the contribution of specific isoforms
      of PKC will be discussed. Finally, it will be shown that Purkinje cell dendritic
      development in slice cultures does not depend on the activation of glutamate
      receptors and appears to be independent of the presence of the neurotrophin BDNF.
      These studies indicate that the initial outgrowth of the Purkinje cell dendritic
      tree can occur in the absence of signals derived from afferent fibers, but is
      under control of PKC signaling.

PMID- 15580763
TI  - Changes in the renal handling of urea in sheep on a low protein diet exposed to
      saline drinking water.
AB  - Previous trials have demonstrated that sheep on a low protein diet and free
      access to water, and sheep dosed with boluses of NaCl intraruminally also with
      free access to water, showed decreases in urea loss via the urine compared to
      control animals. We monitored urea excretion in sheep on a relatively poor
      protein diet when they were exposed to saline drinking water, i.e. they were
      unable to vary their intake of NaCl:water. Sheep on isotonic saline drinking
      water (phase 3) excreted significantly more urea via the urine (284 mM/day)
      compared to phase 1 when they were on non-saline drinking water (urea excretion =
      230 mM/day) and phase 2 when they were on half isotonic saline drinking water
      (urea excretion = 244 mM/day). This finding was explained by the high glomerular
      filtration rate (GFR) 91.9 l/day, compared to 82.4 l/day (phase 1) and 77.9 l/day
      (phase 2), together with a significantly raised fractional excretion of urea
      (FEurea) (51.1 %) during this phase, and was in spite of the significantly lower
      plasma concentrations of urea in phase 3 compared to phase 1. The FEurea probably
      results from the osmotic diuresis caused by the salt. There were indications of a
      raised plasma antidiuretic hormone (ADH) concentration and this would have
      opposed urea loss, as ADH promotes urea reabsorption. However, this ADH effect
      was probably counteracted to some extent by a low plasma angiotensin II
      concentration, for which again there were indications, inhibiting urea
      reabsorption during the phases of salt loading. As atrial natriuretic peptide
      both increases GFR and decrease sodium reabsorption from the tubule, it was
      probably instrumental in causing the increase in GFR and the increase in the
      fractional excretion of sodium (FE(Na)).

PMID- 15580764
TI  - Parasites of South African wildlife. XVIII. Cooperia pigachei n. sp. (Nematoda:
      Cooperiidae) from the mountain reedbuck, Redunca fulvorufula (Afzelius, 1815).
AB  - A new species of Cooperia, for which the name Cooperia pigachei n. sp. is
      proposed, was recovered from a mountain reedbuck, Redunca fulvorufula, from the
      Sterkfontein Dam Nature Reserve, Free State Province, and is described and
      illustrated. It is close to Cooperia neitzi Monnig, 1932 and the South African
      race of Cooperia rotundispiculum in having more than 14 longitudinal cuticular
      ridges and in that the lateral cervical synlophe is of the closed type. The new
      species differs from all the other species of the genus in that the lateral
      branches of the dorsal ray are large and T-shaped. The spicules are robust, over
      0.3 mm long and have large, curved shoes on their tips.

PMID- 15580765
TI  - Evaluation of isometamidium levels in the serum of sheep and goats after
      prophylactic treatment against trypanosomosis.
AB  - Isometamidium chloride has been used for the control of trypanosomosis in animals
      for over 36 years, but recently there have been reports of prophylaxis failure
      under natural conditions. In this study, use of the drug for prophylactic purpose
      against trypanosomosis in small ruminants was investigated. Forty-two sheep and
      44 goats were divided into four treatment groups. Groups 1 and 2 were treated
      with isometamidium chloride (Samorin, Rhone Merieux, Lyon, France) at 3-month
      intervals while groups 3 and 4 were used as controls. All the animals were
      exposed to natural tsetse challenge and monitored for serum isometamidium levels
      and anti-trypanosome antibodies. Seven days after drug administration,
      isometamidium levels were significantly higher in goats 13.7+/-0.07 ng/ml than in
      sheep 6.2+/-0.06 ng/ml. However, the elimination half-life in the sheep was
      14.2+/-0.92 days and was significantly higher (P> 0.05) than that of the goats
      12+/-0.5 days. This study established that isometamidium metabolism differs
      between sheep and goats and this difference may have important implications in
      high tsetse challenge areas.

PMID- 15580766
TI  - A retrospective study of the prevalence and seasonal variation of Fasciola
      gigantica in cattle slaughtered in the major abattoirs of Zimbabwe between 1990
      and 1999.
AB  - A retrospective study covering a period of 10 years (1990--1999) was conducted
      using post mortem meat inspection records of the Veterinary Department
      Information Management Unit at Harare to determine the prevalence and seasonal
      variation of bovine fasciolosis in Zimbabwe. Records of monthly and annual
      returns from five major abattoirs were examined in regard to total cattle
      slaughtered and the corresponding number of livers condemned due to Fasciola
      gigantica infection. Prevalence of fasciolosis was calculated as the number of
      cattle found to be infected with F gigantica, expressed as a percentage of the
      number of cattle slaughtered. Seasonal variations in the prevalence were examined
      by pooling respective monthly condemnation data over a 10-year (1990--1999)
      period. A total of 2,474,232 cattle were slaughtered during this period and
      917,565 (37.1%) of these cattle were infected with F. gigantica. The pattern of
      distribution of F. gigantica was significantly higher in cattle originating from
      catchment areas of high rainfall than in those of relatively low rainfall, and in
      those slaughtered during the wet season than those slaughtered during the dry
      season (P< 0.05). Based on the study findings a control programme for the disease
      in Zimbabwe is suggested.

PMID- 15580767
TI  - Endemic stability for Theileria parva infections in Ankole calves of the Ankole
      ranching scheme, Uganda.
AB  - A population-based study was carried out on the Ankole ranching scheme in south
      west Uganda with the aim of determining the endemic status of Theileria parva
      infections. For this purpose, the age-related sero-prevalence of T. parva and the
      specific calf mortality associated with the parasite were assessed. Blood samples
      were collected from 931 Ankole calves of up to 12 months of age from 81 randomly
      selected herds. The relationship between rainfall pattern and whole-body
      Rhipicephalus appendiculatus counts was determined. The influence of tick control
      practices on East Coast fever-related calf mortality, and sero-positivity were
      also determined. A significant (r2 = 0.76, P = 0.000) association between R.
      appendiculatus counts and rainfall was observed. There was no significant (P >
      0.05) association between theileriosis-related calf mortality, sero-positivity
      and the different tick control practices. Antibody prevalence based on the PIM
      ELISA was above 70% among calves of 6 months of age in 96% in all the herds.
      Theileria parva-related calf mortality determined by repeated herd visits and
      farm records ranged between 0 % and 5.4 %. It was concluded that endemic
      stability for theileriosis, caused by T. parva, existed in the study area, and
      that the risk of the occurrence of economically important outbreaks of East Coast
      fever in indigenous cattle was regarded as minimal under the prevailing
      conditions.

PMID- 15580768
TI  - Ventricular dyssynchrony as a cause of structural disease in the heart of Dorper
      sheep.
AB  - Ventricular dyssynchrony is a disturbance of the normal, organized
      electromechanical coupling of the two ventricles. This condition has many causes,
      such as left bundle branch block, ventricular preexcitation, right ventricular
      pacing and right ventricular premature ventricular complexes (PVCs). Ventricular
      dyssynchrony has many adverse haemodynamic effects on the left ventricle and we
      wanted to know whether these adverse haemodynamic effects might have any
      structural consequences on the left ventricles of such hearts. Six healthy Dorper
      wethers were subjected to numerous right ventricular PVCs to induce ventricular
      dyssynchrony in order to determine whether any structural consequences will occur
      in the left ventricles of these hearts. Myocarditis in the musculature of the
      left ventricles of all six these hearts was seen.

PMID- 15580769
TI  - Comparison of three different media for freezing of epididymal sperm from the
      African buffalo (Syncerus caffer) and influence of equilibration time on the post
      thaw sperm quality.
AB  - Assisted reproductive techniques might prove themselves useful tools in producing
      buffaloes free of specific diseases (BFSD), which are in demand in South Africa.
      Freezing protocols for African buffalo semen must not only result in good post
      thaw qualities, but must also be practical. Epididymal sperm from six mature
      African buffalo bulls was collected, diluted with three different semen extenders
      and frozen. Pre-freezing equilibration times between 2 and 9 h were tested. Total
      and progressive motility, longevity and acrosomal integrity were measured and
      compared. The use of Triladyl proved to result in better post-thaw parameters
      than the other two diluents. Equilibration times of between 4 and 9 h did not
      influence post-thaw sperm qualities significantly. For some of the treatments,
      exposure to semen extenders before freezing for less than 4 h resulted in
      inferior post-thaw semen parameters.

PMID- 15580770
TI  - Cross-sectional estimation of Babesia bovis antibody prevalence in cattle in two
      contrasting dairying areas in Tanzania.
AB  - The crude prevalence of antibodies to Babesia bovis infection in cattle was
      estimated by serology using indirect ELISA during the period January to April,
      1999. Sera were obtained from 1,395 dairy cattle (of all ages, sexes and breeds)
      on smallholder farms, the majority being kept under a zero grazing regime. The
      crude prevalence of antibodies to Babesia bovis was 6 % for Tanga and 12 % for
      Iringa. The forces of infection based on the age sero-prevalence profile, were
      estimated at six for Iringa and four for Tanga per 100 cattle years-risk,
      respectively. Using random effect logistic regression as the analytical method,
      the factors (variables) of age, source of animals and geographic location were
      hypothesised to be associated with sero-positivity of Babesia bovis in the two
      regions.

PMID- 15580771
TI  - Epidemiology of gastrointestinal helminths infections in Dorper sheep in a semi
      arid area of Kenya.
AB  - A survey on the prevalence and intensity of infection with gastrointestinal
      helminths of Dorper sheep in relation to age and weather factors was carried out
      on a ranch in Kajiado district, a semi-arid area of Kenya for a period of 13
      months (May 1999 to May 2000). Faecal samples from lambs (3 months to 1 year),
      yearlings (1-2 years) and adult breeding ewes (2-4 years) were examined for
      helminth egg output and helminth genus composition at 3-week intervals. The
      results indicated that the prevalence of strongyle and tapeworms infections were
      highest for lambs, followed by the adult breeding ewes and then for the
      yearlings. In all age groups the proportions of infected animals were higher
      during the wet season than in the dry season for both nematodes and tapeworms.
      The mean strongyle egg counts were higher during the dry season for lambs, but
      were higher during the wet season for the other age groups. Mixed strongyle
      infections were detected, with Trichostrongylus (55 %), Haemonchus (28 %),
      Cooperia (10.5 %) and Oesophagostomum (6.5 %) being the most frequently
      encountered genera throughout the study period. The trends in strongyle faecal
      egg counts indicated the occurrence of hypobiosis, with resumption of development
      towards the end of the dry season and at the onset of the short rains in October
      and November. Self-cure was also observed in September and November in all age
      groups, although less frequently in lactating ewes. The prevalence and
      intensities of infection with gastrointestinal helminths in this area appeared to
      be influenced by the age of the host and weather factors.

PMID- 15580772
TI  - Protective levels of canine distemper virus antibody in an urban dog population
      using plaque reduction neutralization test.
AB  - Blood samples from 50 dogs were collected at three veterinary clinics in Ibadan
      and Abuja, Nigeria and the serum from each sample was evaluated serologically for
      neutralizing antibodies against canine distemper virus (CDV) by the highly
      sensitive plaque reduction (PRN) neutralization assay. Thirteen dogs had plaque
      reduction neutralization titres of 0-100, seven had titres of 100-1,000 while 30
      had titres ranging from 1,000-6,000. The PRN titres of vaccinated dogs were found
      to be significantly higher than unvaccinated dogs. The widespread use of the
      highly reproducible PRN test for the evaluation of antibody response to CDV may
      be very important in the generation of international CDV positive serum standards
      that should help to improve pre-and post-vaccination testing of dogs worldwide.

PMID- 15580773
TI  - Protective efficacy of isometamidium chloride and diminazene aceturate against
      natural Trypanosoma brucei, Trypanosoma congolense and Trypanosoma vivax
      infections in cattle under a suppressed tsetse population in Uganda.
AB  - The protective efficacy of isometamidium chloride (ISMM) and diminazene aceturate
      (DIM) against Trypanosoma brucei, Trypanosoma congolense and Trypanosoma vivax
      infections in cattle under a suppressed tsetse population was assessed in
      southeast Uganda. A total of 66 and 57 trypanosome-infected cattle were treated
      with ISMM and DIM, respectively together with 177 trypanosome-free animals not
      treated were followed for 12 months, checked every 4 weeks. There was no
      statistical difference in the mean time to infection with any trypanosome species
      in animals treated with ISMM or DIM. However, the mean time to trypanosome
      infection was significantly longer for treated animals than controls. The mean
      time to infection with each of the three trypanosome species differed
      significantly, with the average time to T. vivax infection the lowest, followed
      by T. congolense and then T. brucei. The protective efficacy of DIM was as good
      as that of ISMM; implying curative treatments against trypanosomosis are
      sufficient for combination with tsetse control. Isometamidium chloride or DIM had
      the highest impact on T. brucei and T. congolense infections in cattle.

PMID- 15580774
TI  - Towards the establishment and standardization of a veterinary antimicrobial
      resistance surveillance and monitoring programme in South Africa.
AB  - The objective of this study was to establish a repeatable, standardized
      laboratory procedure for monitoring the development of antimicrobial resistance
      in bacteria isolated from animals and food of animal origin in South Africa, with
      reagents prepared in-house. The emergence of resistance and the spread of
      resistant bacteria can be limited by implementing a veterinary antimicrobial drug
      policy, in which inter alia systematic monitoring and prudent use play essential
      roles. The bacteria included in this study represented three different
      categories, namely zoonotic bacteria (Salmonella), indicator bacteria
      (Escherichia coli, Enterococcus faecalis and Enterococcus faecium) and veterinary
      pathogens (Mannheimia haemolytica). Thirty isolates of each species were
      collected with the aim of standardizing the laboratory methodology for a future
      national veterinary surveillance and monitoring programme. Susceptibility to ten
      selected antimicrobial drugs was determined by means of minimum inhibitory
      concentrations (MICs) using the microdilution method. The method according to the
      National Committee for Clinical Laboratory Standards was used as the standard.
      Multi-well plates containing varying dilutions of antimicrobial drugs and
      prepared in-house for MIC determinations, yielded repeatable results. Storage of
      plates for 2 months at -70 degrees C did not influence results meaningfully.
      Within this limited sample of bacteria, MIC results did not indicate meaningful
      resistance against any of the ten selected antimicrobial drugs. The findings of
      the study will be used to establish a national veterinary antimicrobial
      resistance surveillance and monitoring programme in South Africa. To allow for
      international comparison of data, harmonisation of the surveillance and
      monitoring programme in accordance with global trends is encouraged. Ideally it
      should be combined with a programme monitoring the quantities of antimicrobial
      drugs used. The aim is to contribute to slowing down the emergence of resistance
      and the problems associated with this phenomenon by means of the rational use of
      antimicrobial drugs.

PMID- 15580775
TI  - Yolk sac utilization in ostrich (Struthio camelus) chicks.
AB  - The mass of residual yolk sac expressed as a percentage of initial mass of the
      egg from which the chick hatched decreased sharply in the first 2 days post
      hatching. A gradual reduction occurred between 3 and 10 days after which a sharp
      decline was noted between 11 and 13 days post-hatching. The highest number of
      chicks with unabsorbed yolk sac was noted on day 5 post-hatching followed by days
      6 and 7. Chick mortality followed the same pattern. The dynamics, causes and
      clinical consequences of yolk sac utilization are discussed.

PMID- 15580776
TI  - RNA interference: past, present and future.
AB  - RNA interference (RNAi) is the sequence-specific gene silencing induced by double
      stranded RNA. RNAi is mediated by 21-23 nucleotide small interfering RNAs
      (siRNAs) which are produced from long double-stranded RNAs by RNAse II-like
      enzyme Dicer. The resulting siRNAs are incorporated into a RNA-induced silencing
      complex (RISC) that targets and cleaves mRNA complementary to the siRNAs. Since
      its inception in 1998, RNAi has been demonstrated in organisms ranging from
      trypanosomes to nematodes to vertebrates. Potential uses already in progress
      include the examination of specific gene function in living systems, the
      development of anti-viral and anti-cancer therapies, and genome-wide screens. In
      this review, we discuss the landmark discoveries that established the contextual
      framework leading up to our current understanding of RNAi. We also provide an
      overview of current developments and future applications.

PMID- 15580777
TI  - What do proton motive force driven multidrug resistance transporters have in
      common?
AB  - The extensive progress of genome sequencing projects in recent years has
      demonstrated that multidrug resistance (MDR) transporters are widely spread among
      all domains of life. This indicates that they play crucial roles in the survival
      of organisms. Moreover, antibiotic and chemotherapeutic treatments have revealed
      that microorganisms and cancer cells may use MDR transporters to fight the
      cytotoxic action of drugs. Currently, several MDR extrusion systems are being
      investigated in detail. It is expected that understanding of the molecular basis
      of multidrug recognition and the transport mechanisms will allow a more rational
      design of new drugs which either will not be recognized and expelled by or will
      efficiently inhibit the activity of the MDR transporters. MDR transporters either
      utilize ATP hydrolysis or an ion motive force as an energy source to drive drugs
      out of the cell. This review summarizes the recent progress in the field of
      bacterial proton motive force driven MDR transporters.

PMID- 15580778
TI  - The genome of model malaria parasites, and comparative genomics.
AB  - The field of comparative genomics of malaria parasites has recently come of age
      with the completion of the whole genome sequences of the human malaria parasite
      Plasmodium falciparum and a rodent malaria model, Plasmodium yoelii yoelii. With
      several other genome sequencing projects of different model and human malaria
      parasite species underway, comparing genomes from multiple species has
      necessitated the development of improved informatics tools and analyses. Results
      from initial comparative analyses reveal striking conservation of gene synteny
      between malaria species within conserved chromosome cores, in contrast to reduced
      homology within subtelomeric regions, in line with previous findings on a smaller
      scale. Genes that elicit a host immune response are frequently found to be
      species-specific, although a large variant multigene family is common to many
      rodent malaria species and Plasmodium vivax. Sequence alignment of syntenic
      regions from multiple species has revealed the similarity between species in
      coding regions to be high relative to non-coding regions, and phylogenetic
      footprinting studies promise to reveal conserved motifs in the latter. Comparison
      of non-synonymous substitution rates between orthologous genes is proving a
      powerful technique for identifying genes under selection pressure, and may be
      useful for vaccine design. This is a stimulating time for comparative genomics of
      model and human malaria parasites, which promises to produce useful results for
      the development of antimalarial drugs and vaccines.

PMID- 15580779
TI  - Manipulating the Plasmodium genome.
AB  - Genome manipulation, the primary tool for assigning function to sequence, will be
      essential for understanding Plasmodium biology and malaria pathogenesis in
      molecular terms. The first success in transfecting Plasmodium was reported almost
      ten years ago. Gene-targeting studies have since flourished, as Plasmodium is
      haploid and integrates DNA only by homologous recombination. These studies have
      shed new light on the function of many proteins, including vaccine candidates and
      drug resistance factors. However, many essential proteins, including those
      involved in parasite invasion of erythrocytes, cannot be characterized in the
      absence of conditional mutagenesis. Proteins also cannot be identified on a
      functional basis as random DNA integration has not been achieved. We overview
      here the ways in which the Plasmodium genome can be manipulated. We also point to
      the tools that should be established if our goal is to address parasite
      infectivity in a systematic way and to conduct refined structure-function
      analysis of selected products.

PMID- 15580780
TI  - The apicoplast: a review of the derived plastid of apicomplexan parasites.
AB  - The apicoplast is a plastid organelle, homologous to chloroplasts of plants, that
      is found in apicomplexan parasites such as the causative agents of Malaria
      Plasmodium spp. It occurs throughout the Apicomplexa and is an ancient feature of
      this group acquired by the process of endosymbiosis. Like plant chloroplasts,
      apicoplasts are semi-autonomous with their own genome and expression machinery.
      In addition, apicoplasts import numerous proteins encoded by nuclear genes. These
      nuclear genes largely derive from the endosymbiont through a process of
      intracellular gene relocation. The exact role of a plastid in parasites is
      uncertain but early clues indicate synthesis of lipids, heme and isoprenoids as
      possibilities. The various metabolic processes of the apicoplast are potentially
      excellent targets for drug therapy.

PMID- 15580781
TI  - The surface of the Plasmodium falciparum-infected erythrocyte.
AB  - In order to navigate its complex lifecycle, the malaria parasites must
      interactwith a range of host cells. Examples of this are the invasion of
      hepatocytes by sporozoites and erythrocyte invasion by merozoites. This
      requirement for cell recognition brings with it the need to display cognate
      ligands on the parasite surface, and therefore the capacity of the host to
      develop defences against the infection. Even at a stage where the intracellular
      nature of erythrocyte development would appear to offer an opportunity for the
      parasite to be immunologically "silent", parasite-derived proteins are found on
      the surface of the infected erythrocyte. This review will discuss the proteins
      found on or associated with the surface of the infected erythrocyte and the
      resulting phenotypes.

PMID- 15580782
TI  - Responses of cariogenic streptococci to environmental stresses.
AB  - To persist in the oral cavity, bacteria must be able to tolerate rapid and
      substantial environmental fluctuations, particularly in pH and nutrient source
      and availability. Various species of Streptococcus, one of the most abundant
      genera in the mouth, are associated with oral health, as well as with dental
      caries. Cariogenic streptococci depend on a biofilm lifestyle for survival and
      persistence in the oral cavity and have developed sophisticated mechanisms to
      cope with environmental stresses. Here, we analyze the primary factors that allow
      these bacteria to emerge as significant members of tooth biofilms during adverse
      conditions. Our focus is on the molecular mechanisms of biofilm formation, stress
      tolerance and sugar metabolism by pathogenic oral streptococci, mainly
      Streptococcus mutans. Overlaps in the roles and regulation of these virulence
      attributes are highlighted and areas of research that deserve further
      investigation are proposed.

PMID- 15580783
TI  - Control of ribosome synthesis during the cell division cycles of E. coli and
      Synechococcus.
AB  - The regulation of ribosome synthesis has been investigated for nearly five
      decades. In earlier studies, the control of rRNA synthesis in bacteria was found
      to be dependent on nutrient composition of the growth media or cell growth rates,
      and these observations led to the growth rate-dependent regulation model. Also
      developed were stringent control, feedback ribosome synthesis, passive
      regulation, and antitermination models. Current evidence indicates that upstream
      (UP) element, molecular effectors, ppGpp and iNTP (initiating nucleoside
      triphosphate), and trans-acting proteins, Fis and H-NS, play important roles in
      the control of rRNA synthesis in response to changing nutritional environments.
      The mechanisms for the ribosome feedback regulation, and growth rate-dependent
      controls of rRNA synthesis remain to be determined despite numerous
      investigations. r-protein synthesis can be controlled by translational coupling,
      translation repression, or premature transcription termination. In Synechococcus,
      a photoautotroph, ribosome synthesis occurs early in the cell cycle as programmed
      events under conditions that support balanced growth. Periods of r-protein
      synthesis occur before rRNA synthesis periods, and rRNA synthesis is stimulated
      by a light-activated gene regulatory protein. These observations suggest that
      gene regulatory proteins are involved in the coordinate regulation of ribosome
      assembly in Synechococcus.

PMID- 15580784
TI  - Strategies for reducing exposure to environmental tobacco smoke, increasing
      tobacco-use cessation, and reducing initiation in communities and health-care
      systems. A report on recommendations of the Task Force on Community Preventive
      Services.
AB  - Reducing tobacco-related morbidity and death is an ongoing challenge for health
      care providers, health-care systems, and public health programs. Interventions
      are available that a) reduce exposure to environmental tobacco smoke, b) reduce
      tobacco-use initiation, and c) increase tobacco-use cessation. The Task Force on
      Community Preventive Services has conducted systematic reviews on 14 selected
      interventions, which are appropriate for communities and health-care systems, and
      has made recommendations regarding use of these interventions. This report
      summarizes the recommendations, identifies sources that offer full reviews of the
      interventions and details about applying the interventions locally, and provides
      an update of the Task Force's work.

PMID- 15580785
TI  - The epidemiology of El Nino.

PMID- 15580786
TI  - Diabetic retinopathy.

PMID- 15580787
TI  - Glycemic control in type 2 diabetes mellitus.

PMID- 15580788
TI  - Screening and treatment of diabetic renal disease.

PMID- 15580789
TI  - Coronary artery disease and cerebrovascular disease prevention in diabetes
      mellitus: early identification and aggressive modification of risk factors.
AB  - Risk factor modification for CVD is an established, effective strategy in patient
      care. Risk stratification is used to set treatment goals. Lifestyle modification
      and supplemental pharmacologic therapy are used to accomplish the goals. Patients
      with DM start with one risk factor, often have additional risk factors, and have
      higher rates of existing CVD. Vigilance is required in identifying risk factors
      and persistence in management is often necessary to successfully modify the
      important risk factors.

PMID- 15580790
TI  - Practical primary care diabetic foot screening.

PMID- 15580791
TI  - Provider guidelines for improving diabetes self-management.

PMID- 15580792
TI  - Diabetes legislation, programs and projects.

PMID- 15580793
TI  - LEAP Program (Lower Extremity Amputation Prevention).

PMID- 15580794
TI  - Diabetes case study from a primary care perspective.

PMID- 15580795
TI  - Estimates of diabetes in Rhode Island: a moving target.

PMID- 15580796
TI  - Preview: Lyme disease vaccines.
AB  - Lyme disease is a tick-borne spirochetal disease that is common in Rhode Island.
      The OSP A based vaccine against Lyme disease that has been shown effective in
      animal models has now been tested by two manufacturers in thousands of people.
      The vaccines appear to be safe and effective. When the vaccines become available
      to physicians, there should be strong demand in Rhode Island, especially in the
      southern part of the state where there is a high degree of public awareness and
      experience with Lyme disease. Studies of tick populations support surveillance
      data that show a concentration of risk in Washington County with a trend of
      expansion inland. Patients who receive the vaccine should be alerted to the
      likelihood of local reaction and the less likely systemic effects. Additional
      patient education should include awareness of other tick-borne diseases such as
      babesiosis, chrlichiosis, and Rocky Mountain Spotted Fever that are not vaccine
      preventable. Serologic testing for Lyme disease will be affected by the immune
      response to the vaccine. These vaccines have not yet been tested in children.

PMID- 15580797
TI  - Rhode Island monthly vital statistics report. Provisional occurrence data from
      the Division of Vital Records.

PMID- 15580798
TI  - Tarasoff: Duty to warn? Duty to protect?

PMID- 15580799
TI  - "Norwalk-like viruses". Public health consequences and outbreak management.
AB  - "Norwalk-like viruses" (NLVs) cause outbreaks of gastroenteritis and are spread
      frequently through contaminated food or water. Molecular diagnostics now enables
      detecting viruses in clinical and environmental specimens, linking of NLV strains
      causing outbreaks in multiple geographic locations, and tracing them to their
      sources in contaminated food or water. This report reviews recent advances in NLV
      detection and provides guidelines and recommendations for investigating NLV
      related outbreaks, including specimen collection and disease prevention and
      control. This report also updates information provided in CDC's previously
      published, Viral Agents of Gastroenteritis: Public Health Importance and Outbreak
      Management (MMWR 1990;39 [No. RR-5]: 1-24). These CDC recommendations are
      intended for public health professionals who investigate outbreaks of acute
      gastroenteritis but could be useful in academic and research settings as well.

PMID- 15580800
TI  - Are women with recent live births aware of the benefits of folic acid?
AB  - Each year, approximately 4,000 pregnancies result in spina bifida or anencephaly,
      serious and often fatal conditions for the newborn. The B vitamin folic acid can
      reduce the incidence of these conditions by 50%-70%. To examine folic acid
      awareness among women who had recently delivered a live-born infant, CDC analyzed
      Pregnancy Risk Assessment Monitoring System (PRAMS) data for 1995-1998. The
      question used to measure awareness was, "Have you ever heard or read that taking
      the vitamin folic acid can help prevent some birth defects?" During the study
      period, overall folic acid awareness increased 15%, from 64% in 1996 to 73% in
      1998, although changes varied by state. Despite this increase, differences in
      folic acid awareness were observed among different groups of women. Women who
      obtained a high school education or less; who were black, Hispanic, or from other
      racial/ethnic groups; who entered prenatal care after the first trimester; and
      whose pregnancies were unintended were less aware of folic acid. This study
      indicates that gaps persist among women in low socioeconomic groups. Overall,
      PRAMS data indicated an increase in folic acid awareness among women with recent
      deliveries. However, this awareness might be too late for the pregnancy that has
      occurred, indicating a continued need to educate all reproductive-aged women
      regarding the need to take folic acid before they become pregnant.

PMID- 15580801
TI  - Successful implementation of perinatal HIV prevention guidelines. A multistate
      surveillance evaluation.
AB  - In 1994, zidovudine (ZDV) was demonstrated to substantially reduce perinatal
      transmission of the human immunodeficiency virus (HIV). Guidelines regarding the
      use of ZDV to reduce transmission and regarding counseling and voluntary testing
      of pregnant women were issued in 1994 and 1995, respectively. Surveillance
      methods were used to evaluate the implementation of these guidelines and to
      understand reasons for continued perinatal transmission of HIV. Population-based
      enhanced perinatal surveillance was used in seven states to collect information
      regarding mother-infant pairs in 1993, 1995, and 1996. Birth registries and
      HIV/Acquired immunodeficiency virus (AIDS) registries were matched to determine
      the number of HIV-infected women with diagnosis before delivery. Supplemental
      epidemiologic information was collected for 1,321 pairs. The estimated total
      number of HIV-infected women giving birth each year was derived from the Survey
      of Childbearing Women, an anonymous serologic survey of the prevalence of HIV
      infection among women giving birth. From 1993 through 1996, the proportion of HIV
      infected women with diagnosis before delivery increased from 70% to 80%. The
      proportion of women with a diagnosis who received ZDV prenatally increased from
      27% to 83% and intrapartum, 6% to 75%; for neonates, the increase was from 8% to
      77%. Overall, 14% of women received no or only one prenatal care visit. A total
      of 36% of women who used illicit drugs during pregnancy had not had prenatal
      care. Of the children who received any ZDV, 8% were infected compared with 16% of
      those who received no ZDV. ZDV, used for treating pregnant HIV-infected women,
      has been rapidly adopted in clinical practice and has reduced the transmission of
      HIV. To achieve continued declines in perinatal transmission of HIV infection,
      continued progress is needed in the following areas: a) increases in the
      proportion of women who receive prenatal care and an HIV diagnosis; and b)
      implementation of rapid testing methods (when licensed rapid tests are available)
      or rapid turnaround of standard tests (expedited EIA tests).

PMID- 15580802
TI  - A method for classification of HIV exposure category for women without HIV risk
      information.
AB  - An increasing number of cases of human immunodeficiency virus (HIV) and acquired
      immunodeficiency syndrome (AIDS) among women is reported to state and territorial
      health departments without exposure risk information (i.e., no documented
      exposure to HIV through any of the recognized routes of HIV transmission).
      Because surveillance data are used to plan prevention and other services for HIV
      infected persons, developing methods to accurately estimate exposure risk for HIV
      and AIDS cases initially reported without risk information and assisting states
      to analyze and interpret trends in the HIV epidemic by exposure risk category is
      important. In this report, a classification model using discriminant function
      analysis is described. The purpose of the classification model is to develop a
      proportionate distribution of exposure risk category for cases among women
      reported without risk information. The distribution was estimated based on
      behavioral and demographic data obtained from interviews with HIV-infected women;
      the interviews were conducted in 12 states during 1993-1996. Variables used in
      the analysis were alcohol abuse, noninjection-drug use, and crack use; year of
      HIV/AIDS diagnosis; age; employment; and region. As a result of the
      classification procedure, nearly all cases among women with no reported risk were
      classified into an exposure risk category: 81%, heterosexual contact; and 16%,
      injection-drug use. These proportions are higher than the current redistribution
      fractions (calculated from risk reclassification patterns and weighted by
      demographic characteristics) and reflect the increasing proportion of cases among
      women attributable to heterosexual contact with an infected partner. This report
      provides one method that could be applied to HIV surveillance data at the
      national level to estimate the proportion of cases in exposure risk categories.
      However, because the study in this report is limited in sample size and
      geographic representativeness, other models are also needed for adjusting risk
      exposure data at the national, state, and local levels.

PMID- 15580803
TI  - Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on
      Immunization Practices (ACIP), 2001.
AB  - These revised recommendations regarding vaccinia (smallpox) vaccine update the
      previous Advisory Committee on Immunization Practices (ACIP) recommendations
      (MMWR 1991;40; No. RR-14:1-10) and include current information regarding the
      nonemergency use of vaccinia vaccine among laboratory and health-care workers
      occupationally exposed to vaccinia virus, recombinant vaccinia viruses, and other
      Orthopoxviruses that can infect humans. In addition, this report contains ACIP's
      recommendations for the use of vaccinia vaccine if smallpox (variola) virus were
      used as an agent of biological terrorism or if a smallpox outbreak were to occur
      for another unforeseen reason.

PMID- 15580804
TI  - Progressing toward tuberculosis elimination in low-incidence areas of the United
      States. Recommendations of the Advisory Council for the Elimination of
      Tuberculosis.
AB  - In 2000, 22 states had tuberculosis (TB) incidence rates less than or equal to
      the Advisory Council for the Elimination of Tuberculosis (ACET) year-2000 interim
      objective of 3.5 cases/100,000 population, which is defined as low incidence.
      These states reported 1,949 TB cases, 11.9% of the national total of 16,377 cases
      in 2000. Health departments in low-incidence states, and in low-incidence regions
      within states with higher rates, need distinctive strategies, based on their
      specific epidemiologic characteristics, for maintaining skills and resources for
      finding increasingly rare TB cases, containing outbreaks, and ending
      transmission. Capacity for all the essential components of a TB prevention and
      control program must be retained at local, state, and national levels; failure to
      do so increases the risk of a new TB resurgence. In low-incidence areas,
      especially important are an adequate public health infrastructure and creative
      integration of resources, some of which until now have not played a role in TB
      control. Operational research is needed for determining the most efficient
      control measures. Eventually, with continued success in eliminating TB, low
      incidence will be attainable in all states, and the nation will profit from the
      lessons learned in the current low-incidence states.

PMID- 15580805
TI  - The effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acids on
      delta4-desaturation in HepG2 cells.
AB  - The objective of this study was to determine the effects of cis-9, trans-11 and
      trans-10, cis-12 CLA on the delta4-desaturation process in HepG2 cells.
      Experiments were conducted in which HepG2 cells were incubated with 25 micromol/L
      of those fatty acids and the concentrations of (n-6) and (n-3) polyunsaturated
      fatty acids in phosphatidyl choline and phosphatidyl ethanolamine were
      determined. In the presence of eicosapentaenoic acid, cells treated with trans
      10, cis-12 CLA had a lower ratio of docosahexaenoic acid [22:6 (n-3)], the
      product of delta4-desaturation, to docosapentaenoic acid [22:5 (n-3)], the
      substrate of delta4-desaturation in both phospholipids, than control cells or
      cells treated with cis-9, trans-11 CLA (p < 0.05). This suggests that trans-10,
      cis-12 CLA suppresses the delta4-desaturation process in HepG2 cells.

PMID- 15580806
TI  - Meat and meat products consumption in Italy: contribution to trace elements, heme
      iron and selected B vitamins supply.
AB  - This study was undertaken to estimate the contribution of meat and meat products
      consumption to the daily intakes of trace elements (Fe, Zn, Cu, Se), heme iron,
      and selected B vitamins (thiamine, riboflavin, niacin) in Italy. Meat and meat
      products were selected on the basis of their consumption frequency reported by
      the most recent nationwide dietary individual survey carried out in Italy (INN-CA
      study). The daily intakes of total iron and heme iron were 1.65 and 1.13
      mg/person/day. Zinc intake was 3.65 mg/person/day. Beef made the main
      contribution to iron, heme iron, and zinc daily intakes. Copper daily intake was
      107.3 microg/person/day, with meat products provided the highest contribution (40
      microg/person/day). Daily intake of selenium (7.14 microg/person/day) was
      provided mainly by poultry consumption. Thiamine intake was 228
      microg/person/day, and meat products were the main source (110
      microg/person/day). Riboflavin intake was 136 microg/person/day, with both beef
      and meat products as the main contributors (40 microg/person/day). Niacin intake
      was 7.53 mg/person/day, and poultry was the main source (2.28 mg/person/day).
      Meat and meat products were a valuable source of micronutrients, supplying 47,
      48, and 24% of zinc, niacin, and thiamin daily requirements, respectively, and
      over 10% of iron, copper, selenium, and riboflavin daily average requirement
      values of the italian RDAs calculated for the population involved in the survey
      (INN-CA study).

PMID- 15580807
TI  - Dietary fiber suppresses elevation of uric acid and urea nitrogen concentrations
      in serum of rats with renal dysfunction induced by dietary adenine.
AB  - This study was conducted to examine the effects of several kinds of dietary fiber
      (DF) with different physical properties on the elevation of uric acid and urea
      nitrogen concentrations in serum of rats induced by dietary adenine. DF decreased
      an uptake of 14C-labeled adenine in the rat jejunum in vitro, but the reduction
      varied with the physical property of DF. Male Wistar rats (3 weeks old) were fed
      a diet with or without a 0.4% adenine and a 5% DF (cellulose, chitin, chitosan,
      or xanthan gum) for 20 days. Feeding of adenine in the fiber-free group elevated
      the concentrations of uric acid, creatinine, and urea nitrogen in serum, but
      decreased the excretions of these compounds into urine and increased the amounts
      of 2,8-dihydroxyadenine (2,8-DHA) in kidney and urine. The test DF was found to
      suppress the elevation of uric acid, creatinine, and urea nitrogen concentrations
      in serum induced by dietary adenine, and to mitigate the decreased excretions of
      these compounds into urine and the increased retention of 2,8-DHA in kidney and
      urine. This phenomenon was remarkable in the xanthan gum group. These results
      suggest that DF suppresses the elevation of uric acid and urea nitrogen
      concentrations in serum by attenuating the absorption of dietary adenine.

PMID- 15580808
TI  - Effect of nutrition education and diet modification in iron depleted preschool
      children in nurseries in Tehran: a pilot study.
AB  - In view of the high prevalence of iron deficiency in preschool children and its
      consequences, this study was carried out to examine the effect of nutrition
      education and dietary modification on 438 two- to six-year-old nursery school
      children in Tehran in 1999. Sixty-two children who were judged anemic, iron
      depleted, or having low iron stores were randomly allocated to "control,"
      "dietary modification" (consuming one additional citrus fruit after lunch), and
      "nutrition education" (teaching the mothers proper eating patterns based on the
      food pyramid) groups. Food habits were surveyed, including 24-hour dietary recall
      and food frequency, as well as timing of consumption of special items; this
      survey was carried out for each child before and after intervention. After three
      months, blood samples were taken from the subjects. The prevalence of anemia,
      iron depletion, and low iron stores was 11.4, 62.8, and 15.1% respectively, with
      no significant differences observed in hemoglobin and percent transferrin
      saturation (%TS) between the groups. Mean+/-SD serum ferritin concentrations in
      "control," "diet modification," and "nutrition education" groups were 8.9+/-3.1,
      9.5+/-3.7, and 6.9+/-2.3 microg/dL. The same figures at the end of intervention
      were 6.9+/-3.5, 11.2+/-5, and 10.7+/-5.9 microg/dL, respectively. Analysis of
      variance showed ferritin concentrations to be significantly different, in that
      there was a reduction in the control and elevation in the nutrition education
      groups. There was no significant difference in %TS before and after the
      intervention. During three months of intervention, changes in frequency of fruit
      and fruit juice intake after the meals in nutrition education and diet
      modification groups were significantly correlated to serum ferritin alteration.
      Frequency of fruit juice intake (rich in vitamin C) after meals (at least five
      times a week) can significantly increase serum ferritin within three months.
      Therefore, educating mothers of iron-deficient children while increasing the iron
      stores in children can prevent the recurrence of iron deficiency and result in
      general child well-being.

PMID- 15580809
TI  - Plasma-kinetic characteristics of purified and isolated green tea catechin
      epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy
      volunteers.
AB  - This randomized, double-blind, placebo-controlled study assessed the safety,
      tolerability, and plasma-kinetic behavior of 94% pure crystalline
      epigallocatechin gallate (EGCG) after ten days' repeated dosing in 36 healthy
      male volunteers. Each of the three treatment groups consisted of 12 subjects;
      nine of them received oral EGCG in one dose of 200, 400, or 800 mg daily, and
      three received a placebo. Blood samples for plasma-kinetic EGCG characterization
      were taken on day 1 and day 10. Kinetic parameters for rate and extent,
      elimination half-lives, and accumulation factor (R) were determined and compared
      between day 1 and day 10 for each dosage group. Orally administered EGCG is
      rapidly absorbed from the gut. Dose linearity was applied for single-dose
      application (day 1). After repeated dosing (day 10) dose linearity was applied
      between the 200 mg and 400 mg group. Dose escalation to 800 mg was more than dose
      proportional in rate and extent, and statistically different from the 200 mg and
      400 mg group. An increase in elimination half-life (t1/2.z) and in the
      accumulation factor (R) in the 800 mg dosage group indicates dose-dependent
      saturation of capacity-limited excretion routes or an increase of hepato-duodenal
      re-circulation. Ten days' repeated administration of oral doses of EGCG of up to
      800 mg per day were found to be safe and very well tolerated.

PMID- 15580810
TI  - Modulation of cytokine production by low and high retinoid diets in ovalbumin
      sensitized mice.
AB  - Retinoids modulate many physiological processes such as the differentiation and
      growth of different cell types, including cells from the immune system. We have
      previously shown that retinoids modulate IgE production in vitro and in vivo. In
      the present study we investigated the effects of retinoids in non-sensitized and
      ovalbumin-sensitized mice that were fed for 11 weeks with three different vitamin
      A (VA) diets: a) VA-deficiency diet, b) base diet, and c) base diet supplemented
      with 0.5% all-trans-retinoic acid (ATRA). Phorbol-myristate-acetate
      (PMA)/ionomycin-stimulated SMC (splenic mononuclear cells) from mice fed with
      ATRA and the vitamin A-deficient diet group showed increased interleukin-4 (IL-4)
      responses in non-sensitized mice. After ovalbumin sensitization in the VA
      deficient and the ATRA supplementation diet groups, no significant effects on IL
      4 production were observed. By contrast, gamma interferon (IFN-gamma production
      from PMA/ionomycin-stimulated SMC was enhanced in the VA-deficient diet group in
      ovalbumin-sensitized mice, and also in non-sensitized mice compared to the base
      and the ATRA-supplemented diet group. The data indicate that VA and retinoid
      content in a diet influences the cytokine response in non-sensitized and also
      ovalbumin-sensitized mice. Therefore these molecules may serve as active
      modulators of cytokine production in vivo that are responsible for the induction
      and persistence of atopic diseases.

PMID- 15580811
TI  - Cardiovascular effects of oral Supplementation of vitamin C, E and folic acid in
      young healthy males.
AB  - Numerous observational studies showed associations of antioxidants (vitamins C
      and E) and folate intake with a reduced risk of cardiovascular disease, but
      randomized controlled clinical trials have generally not supported this
      hypothesis. The objective of this study was to investigate the effects of a daily
      dosage of 1000 mg vitamin C, 800 mg vitamin E, and 10 mg folate on markers of
      vascular function in 31 young healthy male adults. Cardiovascular values after a
      12-week vitamin (14 subjects) or placebo (17 subjects) intervention were compared
      to baseline values. Cardiovascular parameters (blood pressure, stroke volume,
      heart rate, cardiac output, vascular resistance, arterial compliance) were
      measured continuously after an overnight fast under controlled circumstances with
      a Finometer device. Our main finding was a significant decrease (p = 0.03) in
      systolic blood pressure in the experimental group. No statistically significant
      changes were observed within other cardiovascular variables of the experimental
      group, but possible beneficial decreases in diastolic blood pressure and
      increases in arterial compliance after 12 weeks of vitamin supplementation were
      indicated. In conclusion, beneficial effects of antioxidants and folate were
      observed probably because the supplementation was used by young healthy subjects
      under carefully controlled conditions.

PMID- 15580812
TI  - Effect of ascorbic acid and particle size on iron absorption from ferric
      pyrophosphate in adult women.
AB  - The effects of added ascorbic acid and particle size on iron absorption from
      ferric pyrophosphate were evaluated in adult women (9-10 women/study) based on
      erythrocyte incorporation of iron stable isotopes (57Fe or 58Fe) 14 days after
      administration. Three separate studies were made with test meals of iron
      fortified infant cereal (5 mg iron/meal) and the results are presented as
      geometric means and relative bioavailability values (RBV, FeSO4 = 100%). The
      results of study 1 showed that iron absorption was significantly lower from
      ferric pyrophosphate (mean particle size 8.5 microm) than from FeSO4 in meals
      without ascorbic acid (0.9 vs. 2.6%, p < 0.0001, RBV 36%) and in the same meals
      with ascorbic acid added at a 4:1 molar ratio relative to fortification iron (2.3
      vs. 9.7%, p < 0.0001, RBV 23%). Ascorbic acid increased iron absorption from
      ferric pyrophosphate slightly less (2.6-fold) than from FeSO4 (3.7-fold) (p <
      0.05). In studies 2 and 3, RBV of ferric pyrophosphate with an average particle
      size of 6.7 microm and 12.5 pm was not significantly different at 52 and 42% (p >
      0.05), respectively. In conclusion, the addition of ascorbic acid increased
      fractional iron absorption from ferric pyrophosphate significantly, but to a
      lesser extent than from FeSO4. Decreasing the mean particle size to 6.7 microm
      did not significantly increase iron absorption from ferric pyrophosphate.

PMID- 15580813
TI  - Goiter prevalence and urinary iodine excretion in schoolchildren of Jordan.
AB  - Iodine deficiency disorders (IDD) are considered a major health problem in the
      eastern Mediterranean region. In Jordan, an IDD assessment was performed in 1993
      following which, a salt iodization and consumption program was implemented and a
      monitoring survey performed in 2000. In schoolchildren 8 to 10 years of age (2457
      in 1993 and 2601 in 2000) goiter was graded according to WHO classification.
      Urinary iodine was measured in 10% of the children in 1993 and in all of them in
      2000. Percent of iodine consumption in households was assessed by rapid kit test
      in 2000. Prevalence of goiter was 37.7 and 32.1 % and median urinary iodine was
      40 and 154 microg/L, in 1993 and 2000, respectively. Before salt iodization, the
      prevalence of goiter and severity of iodine deficiency was more pronounced in
      rural regions and in the southern part of Jordan. In 2000, all but one
      governorate had a median urinary iodine (MUI) of above 100 microg/L. The
      percentage of urinary iodine levels < 50 microg in two governorates was > 20%.
      Iodine consumption rate of households was 88.3% throughout the country, but was <
      70% in three governorates. It is concluded that moderate and severe IDD existed
      before 1993 in Jordan. Although the iodized salt program has been successful in
      optimizing MUI, the program for the control of IDD needs further improvement.

PMID- 15580814
TI  - Pensacola hospital and patients survive battering by Hurricane Ivan.

PMID- 15580815
TI  - Team approach avoids denials and saves millions.

PMID- 15580816
TI  - Get ready for emphasis on quality measures.

PMID- 15580817
TI  - Simple measures result in big quality improvements.

PMID- 15580818
TI  - New care management model cuts LOS, observation days.

PMID- 15580819
TI  - ED sees 50% reduction in time from triage to ED bed.

PMID- 15580820
TI  - How to unjam your discharge bottlenecks.

PMID- 15580821
TI  - Equine dentistry--what do we really know?

PMID- 15580822
TI  - Comparison of hand-instrumented, heated gutta-percha and engine-driven, cold
      gutta-percha endodontic techniques.
AB  - An in vitro study compared two gutta-percha obturation techniques of the
      mandibular first molar in dogs. The mandibular first molars were instrumented and
      obturated using either K-files and the SuccessFil vertical compaction technique
      or rotary instruments and the Simplifill/guttapercha master cone technique.
      Instrumentation and obturation times were recorded for each tooth. Radiographs
      were used for evaluation of overall appearance of the final fill. A modified
      apical dye leakage technique was used to evaluate the ability of each method to
      provide an adequate barrier to apical leakage. The endodontic technique utilizing
      rotary instruments and Simplifill/gutta-percha master cone required less time and
      provided a better radiographic appearance to the endodontic fill. In addition,
      there was no apical dye leakage associated with this technique compared with a
      44% leakage incidence in teeth treated with K-file instrumentation and
      SuccessFil.

PMID- 15580823
TI  - Symphysiotomy, symphysiectomy, and intermandibular arthrodesis in a cat with open
      mouth jaw locking--case report and literature review.
AB  - A Persian cat was presented with open-mouth jaw locking. It was suspected that
      abnormal extrusion of the maxillary canine teeth caused contact with the
      mandibular canine teeth on closure of the mouth, resulting in levering forces
      that may have led to increased symphyseal mobility, temporomandibular joint
      laxity, rotational movement of the left mandibular body and locking of the left
      coronoid process lateral to the zygomatic arch. Symphysiotomy, symphysiectomy,
      circumferential and interdental wiring, and intraoral resin-based splint
      application were performed to achieve intermandibular arthrodesis. Following
      removal of all devices, no further jaw locking episodes were reported during a 33
      month follow-up period.

PMID- 15580824
TI  - Treatment of an infrabony pocket in an American Eskimo dog.
AB  - This case report describes the use synthetic bone graft particulate and 24% EDTA
      gel to treat an infrabony defect adjacent to the mandibular right first molar
      tooth in an American Eskimo dog. Postoperative examination 33-months following
      surgery showed osseous integration at the infrabony defect and restoration of the
      periodontal ligament space with a small refractory periodontal pocket.

PMID- 15580825
TI  - Supernumerary molar tooth in a horse.

PMID- 15580826
TI  - Canine dental radiography.

PMID- 15580827
TI  - Pharyngostomy endotracheal tube.

PMID- 15580828
TI  - Haptic painting.

PMID- 15580829
TI  - Nanyang Technological University virtual campus.

PMID- 15580830
TI  - The top five problems that motivated my work.

PMID- 15580832
TI  - Haptic rendering--touch-enabled interfaces.

PMID- 15580831
TI  - A decade of applications.

PMID- 15580833
TI  - Synergistic visual/haptic rendering modes for scientific visualization.

PMID- 15580834
TI  - Touch-based haptics for interactive editing on point set surfaces.

PMID- 15580835
TI  - Evaluation of drawing on 3D surfaces with haptics.

PMID- 15580836
TI  - Haptic state-surface interactions.

PMID- 15580837
TI  - Physically accurate haptic rendering with dynamic effects.

PMID- 15580838
TI  - A large haptic device for aircraft engine maintainability.

PMID- 15580839
TI  - Crop art, Part 2.

PMID- 15580840
TI  - The linear accelerator mechanical and radiation isocentre assessment with an
      electronic portal imaging device (EPID).
AB  - Regular checks on the performance of radiotherapy treatment units are essential
      and a variety of protocols has been published. These protocols identify that the
      determination of isocentre must be accurate and unambiguous since both the
      localization of a radiation field on a patient and positioning aids are
      referenced to it. An EPID (BIS 710) with a combined light and radiation
      scintillation detector screen was used to assess mechanical and radiation
      isocentres for different collimator and gantry angles. Crosshair positions within
      light field images were determined from fitted Gaussian intensity profiles and
      then used to calculate the displacement of the mechanical isocentre. For
      comparison, the position of the crosshair was also recorded on a graph paper. The
      radiation field centre was first calculated from the set up geometry for given
      gantry/collimator angles and then compared with measured values to assess the
      displacement of the radiation isocentre. The radiation isocentre was also checked
      by locating a marker, positioned on the couch, on the EPID radiation images for
      different treatment couch angles. The mechanical and radiation isocentres were
      determined from the EPID light field and radiation images respectively with an
      accuracy of 0.3 mm using simple PC based programs. The study has demonstrated the
      feasibility of using the EPID to assess mechanical and radiation isocentres of a
      linear accelerator in a quick and efficient way with a higher degree of accuracy
      achieved as compared to more conventional methods, e.g. the star shot.

PMID- 15580841
TI  - Radiation protection recommendations for I-131 thyrotoxicosis, thyroid cancer and
      phaeochromocytoma patients.
AB  - Iodine-131 patients pose a radiation risk to their family members, carers and
      colleagues. Doses from thyrotoxicosis and thyroid cancer patients undergoing
      standard treatments have been well characterised in the literature. However the
      resulting precautions cannot be easily adapted to circumstances where the patient
      has an unusual affliction, or an atypical family or occupational environment. In
      this study, a model for calculating dose from an I-131 patient is derived from
      first principles. The model is combined with existing results from the literature
      to determine a distance weighting factor between patients and family members.
      This technique reduces the uncertainty in the dose calculations by removing the
      need to guess the unknown patterns of close contact, a problem common to all
      previous dose calculation techniques. Data is presented for four unusual I-131
      treatments; a child thyroid cancer patient, two thyroid cancer dialysis patients
      and a phaeochromocytoma patient. The model is used to calculate appropriate
      periods of restricted contact for these patients. The recommendations provide a
      useful guide for future unusual I-131 treatments.

PMID- 15580842
TI  - An IMRT dose distribution study using commercial verification software.
AB  - The introduction of IMRT requires users to confirm that the isodose distributions
      and relative doses calculated by their planning system match the doses delivered
      by their linear accelerators. To this end the commercially available software,
      VeriSoft (PTW-Freiburg, Germany) was trialled to determine if the tools and
      functions it offered would be of benefit to this process. The CMS XiO
      (Computerized Medical System, St. Louis, MO) treatment planning system was used
      to generate IMRT plans that were delivered with an upgraded Elekta SL15 linac.
      Kodak EDR2 film sandwiched in RW3 solid water (PTW-Freiburg, Germany) was used to
      measure the IMRT fields delivered with 6 MV photons. The isodose and profiles
      measured with the film generally agreed to within +/- 3% or +/- 3 mm with the
      planned doses, in some regions (outside the field) the match fell to within +/-
      5%. The isodose distributions of the planning system and the film could be
      compared on screen, allowing for electronic records of the comparison to be kept
      if desired. The features of this software would be of benefit to an IMRT QA
      program.

PMID- 15580843
TI  - Stereotactic radiosurgery planning with ictal SPECT images.
AB  - This paper is motivated by a clinical requirement to utilise ictal SPECT images
      for target localisation in stereotactic radiosurgery treatment planning using the
      xknife system which only supports CT and MRI images. To achieve this, the SPECT
      images were converted from raw (pixel data only) format into a part 10 compliant
      DICOM CT fileset. The minimum requirements for the recasting of a raw format
      image as DICOM CT or MRI data set are described in detail. The method can be
      applied to the importation of raw format images into any radiotherapy treatment
      planning system that supports CT or MRI import. It is demonstrated that the
      combination of the low spatial resolution SPECT images, depicting functional
      information, with high spatial resolution MRI images, which show the structural
      information, is suitable for stereotactic radiosurgery treatment planning.

PMID- 15580844
TI  - Comparison of computer display monitors for computed radiography diagnostic
      application in a radiology PACS.
AB  - A study to compare the performance of the following display monitors for
      application as PACS CR diagnostic workstations is described. 1. Diagnostic
      quality, 3 megapixel, 21 inch monochrome LCD monitors. 2. Commercial grade, 2
      megapixel, 20 inch colour LCD monitors. Two sets of fifty radiological studies
      each were presented separately to five radiologists on two occasions, using
      different displays on each occasion. The two sets of radiological studies were CR
      of the chest, querying the presence of pneumothorax, and CR of the wrist,
      querying the presence of a scaphoid fracture. Receiver Operating Characteristic
      (ROC) curves were constructed for diagnostic performance for each presentation.
      Areas under the ROC curves (AUC) for diagnosis using different monitors were
      compared for each image set and the following results obtained: Set 1: Monochrome
      AUC = 0.873 +/- 0.026; Colour AUC = 0.831 +/- 0.032; Set 2: Monochrome AUC =
      0.945 +/- 0.014; Colour AUC = 0.931 +/- 0.019; Differences in AUC were attributed
      to the different monitors. While not significant at a 95% confidence level, the
      results have supported a cautious approach to consideration of the use of
      commercial grade LCD colour monitors for diagnostic application.

PMID- 15580845
TI  - Equipotential earthing study: equipotential wiring is unnecessary.
AB  - This study was undertaken to determine the ongoing need for Equipotential (EP)
      earthing as required in AS/NZS 3003, section 4.4.2. A total of 2279 earth points
      were tested in four clinical institutions in Body Protected areas (as defined in
      AS/NZS 3003). Each earth point was tested for potentials existing in the earthing
      in order to assess whether any potentials exceeded the 100 mV requirement of
      AS/NZS 3003 for EP earthing. The voltage measured was 1.21 mV +/- 3.59 mV, (mean
      +/- standard deviation (SD)), with a of 99 % confidence interval between 1.0 mV
      and 1.4 mV. This study suggests that the requirements for EP earthing in section
      4.4.2 of AS/NZS 3003 are unnecessary. It is further suggested that Standards
      Australia review these requirements with the view of withdrawing them from the
      Standard.

PMID- 15580846
TI  - Linear accelerator output variability.
AB  - The Wellington Cancer Centre is equipped with two matched linear accelerators
      (Varian 2100CD) linear accelerators (identified as SN1027 and SN42). Each
      morning, before treatments commence, a radiation therapist carries out an output
      constancy check of the radiation output and every fortnight a physicist measures,
      in a phantom, the delivered radiation dose to check on the machine calibration.
      The daily output checks have been recorded into a database (Argus QA for
      Radiation Oncology) since August 1997 and in June 1998 the fortnightly
      calibration measurements were added. The information in the database, up to April
      2003, has been analysed to consider the quality of the daily constancy checks as
      compared with the fortnightly calibration measurements and whether the data
      contains useful information on machine performance. After allowance for the
      effects of machine recalibration the fortnightly calibration measurements had an
      average standard deviation of 0.4% and the daily constancy checks 0.8%. The daily
      constancy checks had a greater number of large deviations than would be expected
      assuming a normal distribution and were not a good predictor of the need for a
      recalibration. The fortnightly calibration measurements with a much lower spread
      give a reliable indication of the need for a recalibration allowing the adoption
      of a +/- 1% tolerance. Over the period analysed one accelerator (SN42) was
      relatively stable with the output generally drifting between +/- 1% while the
      other (SN1027) had a consistent increase in the average output of about 2.5% per
      year.

PMID- 15580847
TI  - Report on the World Congress on Medical Physics and Biomedical Engineering-
      WC2003.

PMID- 15580848
TI  - Toward a new definition of suicidality? Are we prone to Fregoli's illusion?

PMID- 15580849
TI  - Psychiatric diagnoses and suicide: revisiting the evidence.
AB  - BACKGROUND: The key role of prevention and treatment of mental disorders in the
      prevention of suicide is widely acknowledged. Which specific disorders need to be
      targeted remains to be conclusively demonstrated. AIMS: To re-examine the
      presence of psychiatric diagnosis in cases of completed suicide from a global
      perspective. METHOD: A review of studies reporting diagnoses of mental disorders
      in cases of completed suicide with or without history of admission to mental
      hospitals. RESULTS: Most cases were from Europe and North America (82.2%). The
      majority (98%) of these had a diagnosis of at least one mental disorder. Among
      all diagnoses, mood disorders accounted for 30.2%, followed by substance-use
      related disorders (17.6%), schizophrenia (14.1%), and personality disorders
      (13.0%). CONCLUSIONS: The mental health paradigm in suicide prevention covers
      just a part of the problem. Antisuicide strategies focusing exclusively on the
      identification and treatment of depression need to be reconsidered. In addition
      to this, other mental disorders should be targeted, in particular alcohol-use
      disorders and schizophrenia. More emphasis should also be placed on psychosocial
      and environmental interventions diminishing and counteracting stress.

PMID- 15580850
TI  - Intentional and unintentional injuries across health regions in Alberta, Canada:
      an implication for policy.
AB  - The growing practice of including intentional injuries (suicide and interpersonal
      violence) under the injury control umbrella has produced some controversy. The
      present study was designed to determine whether or not there might be an
      empirical basis for this initiative from an ecological point of view by examining
      the associations among unintentional and intentional injuries across 17
      geographically defined health regions. The study was set in the Province of
      Alberta, Canada, where health services were delivered to a population of 2.96
      million persons in 1999 through 17 regional health authorities. The results of a
      principal components analysis showed that nearly all causes of injury
      hospitalization loaded on a single factor. It was not possible to produce
      separate factors for intentional and unintentional injuries. The strong
      intercorrelation among all measures suggests that there is an empirical basis for
      the view that intentional and unintentional injuries belong under the same
      conceptual umbrella, at least at the ecological level.

PMID- 15580851
TI  - Newspaper reporting of suicide cases in Hong Kong.
AB  - This study addresses the concerns over newspapers' reporting of suicide cases in
      Hong Kong, SAR (Special Administrative Region), using the WHO guidelines on the
      reporting of suicide news as a reference for comparison. We compared the official
      suicide information extracted from the Coroner's Court for the year 2000 with
      newspaper reports on suicides taken from five major Chinese local newspapers,
      which accounted for about 80% of the total circulation in Hong Kong. The type of
      newspaper reporting on suicides was also examined. Newspapers tended to report on
      those suicide victims who suffered relationship problems, whereas those who had
      family problems were significantly underreported. Among the suicides reported in
      the newspapers, 6.2% were found on the front page and the majority of the reports
      were presented pictorially. The reporting of suicides was selective and the
      coverage was incomplete, with student suicides reported excessively. The method
      of reporting for Hong Kong newspapers was not in line with the recommendations of
      the WHO or international best practices on presenting suicide news. For this
      reason we recommend a partnership approach with active participation from the
      media on suicide prevention so that communication professionals can proactively
      participate in suicide prevention work more effectively.

PMID- 15580852
TI  - Recollections of bullying at school and their long-term implications for
      lesbians, gay men, and bisexuals.
AB  - This study explores the relationship between experiences of bullying at school,
      adult mental health status, and symptoms of posttraumatic stress among a sample
      of 119 UK residents who identified as lesbian, gay, or bisexual. Participants
      completed a series of questionnaires that focused upon school experiences,
      suicide ideation at school, sexual history, relationship status and negative
      affect, recent positive and negative life-events, internalized homophobia, and
      symptoms associated with posttraumatic stress. The results suggested that
      posttraumatic stress was a potential issue for 17% of participants who also
      scored significantly higher for depression, and reported having had more casual
      sexual partners than their peers. However, those who were found to exhibit
      symptoms of post-traumatic stress were also more accepting of their sexual
      orientation. A small number of participants used prescription or nonprescription
      drugs, or alcohol to help them cope with memories of bullying. It is suggested
      that posttraumatic stress may be a feature of the adult lives of men and women
      who experienced frequent and prolonged bullying at school as a result of their
      actual or perceived sexual orientation.

PMID- 15580853
TI  - Adolescent suicide myths in the United States.
AB  - In the United States, teen suicide rates tripled over several decades, but have
      declined slightly since the mid-1990s. Suicide, by its nature, is a complex
      problem. Many myths have developed about individuals who complete suicide,
      suicide risk factors, current prevention programs, and the treatment of at-risk
      youth. The purpose of this article is to address these myths, to separate fact
      from fiction, and offer recommendations for future suicide prevention programs.
      Myth #1: Suicide attempters and completers are similar Myth #2: Current
      prevention programs work. Myth #3: Teenagers have the highest suicide rate. Myth
      #4: Suicide is caused by family and social stress. Myth #5: Suicide is not
      inherited genetically. Myth #6: Teen suicide represents treatment failure.
      Psychiatric illnesses are often viewed differently from other medical problems.
      Research should precede any public health effort, so that suicide prevention
      programs can be designed, implemented, and evaluated appropriately. Too often
      suicide prevention programs do not use evidence-based research or practice
      methodologies. More funding is warranted to continue evidence-based studies. We
      propose that suicide be studied like any medical illness, and that future
      prevention efforts are evidence-based, with appropriate outcome measures.

PMID- 15580854
TI  - Deliberate self-harm patients who discharge themselves from the general hospital
      without adequate psychosocial assessment.
AB  - Deliberate self-harm patients who leave the acute hospital environment before the
      completion of psychiatric assessment have an increased risk of subsequent self
      harm. We considered the available data on 50 premature self-discharges identified
      prospectively in a general hospital with a well-developed integrated-care pathway
      for self-harm patients, and compared them to a control group. The self-discharge
      group was found to be more likely to have attempted self-poisoning without
      alcohol intoxication or other forms or combinations of self-harm, and an absence
      of identifiable previous self-harm or prior contact with local specialist
      psychiatric services. The two groups showed no difference in age, sex, or area of
      residence based on community mental health team sectors. It is proposed that
      these findings indicate hypotheses for further studies of why people leave the
      hospital without adequate assessment, and how service design could be improved in
      order to help them.

PMID- 15580855
TI  - Natural suicide rates in nations of the world.

PMID- 15580856
TI  - Suicide research based on Danish registers.

PMID- 15580857
TI  - [From genome to proteome--aim of human proteomics].

PMID- 15580858
TI  - [Microchip technology for SNPs analysis and proteomics].

PMID- 15580859
TI  - [Proteome analysis of transformed cells and transgenic animals].

PMID- 15580860
TI  - [Mass spectrometry-based protein analysis and signaling proteomics].

PMID- 15580861
TI  - [Proteomics and epigenetics learned from Down syndrome model mouse].

PMID- 15580862
TI  - [Biochemistry and structural biology in the post-genome era: search for the
      underlying mechanisms of biological molecules].

PMID- 15580863
TI  - [Two-dimensional electrophoresis and proteomics].

PMID- 15580864
TI  - [Bioinformatics].

PMID- 15580865
TI  - [From proteomics to functional glycomics: importance of functional analysis of
      sugar chains].

PMID- 15580866
TI  - [Proteomics and its role in drug discovery and development].

PMID- 15580867
TI  - [Proteomics of cancer].

PMID- 15580868
TI  - [What is impaired consciousness? Revisiting impaired consciousness as psychiatric
      concept].
AB  - For decades, psychiatrists have considered that concepts of impaired
      consciousness in the study of psychiatry were inconsistent with those applied in
      the field of neurology, in which the usefulness of the concept of consciousness
      has long been seriously doubted. Gloor concluded that the concept of
      consciousness does not further the understanding of seizure mechanisms or brain
      function, which is the current representative opinion of most epileptologists.
      Loss of consciousness tends to be reduced to aggregates of individual impairments
      of higher cognitive functions, and the concept of consciousness is preferably
      avoided by neurologists by assigning various behavioral disturbances during
      disturbed consciousness to particular neuropsychological centers. In contrast,
      psychiatrists, especially those in Europe, are more likely to include phenomena
      involving problems related to phenomenological intentionality in impaired
      consciousness. For the present study, we first divided consciousness into
      vigilance and recursive consciousness, and then attempted to determine what kind
      of impaired consciousness would be an ideal candidate to represent pure
      disturbance of recursive consciousness. Then, 4 patients, 1 each with pure
      amnestic states followed immediately by complex partial seizures, an akinetic
      mutistic state caused by absence status, and mental diplopia as a manifestation
      of postictal psychosis, as well as a patient with Alzheimer's disease who
      gracefully performed Japanese tea ceremony, were studied. Based on our findings,
      we concluded that impaired consciousness as a generic term in general medicine
      does not indicate any unitary entity corresponding to some well-demarcated
      physiological function or constitute a base from which recursive consciousness
      emerges as a superstructure. From that, we stressed that a pure form of
      impairment of recursive consciousness could occur without the impaired
      consciousness named generically in general medicine. Second, following
      observation of an additional 3 cases, descriptions of naissance of the first word
      (taken from the autobiography of Helen Keller), visual object agnosia, and
      chronic schizophrenia with schizophasia were discussed to examine the
      relationship between impairments of recursive consciousness and semantic
      generation dysfunction. Attempts to bridge semantic generation and recursive
      consciousness, performed by psychopathologists such as Bin Kimura and Hiroyuki
      Koide, were also briefly discussed. In light of these case presentations and
      related discussions, we re-examined traditional theories of impaired
      consciousness, including Mayer-Gross's Gestalt theory, later replaced by Conrad
      and Henri Ey's theory related to intentionality. Furthermore, we attempted to
      link Denett's theory of consciousness to those traditional theories as well as to
      our own postulations, and neuropsychological data such as those of implicit
      memory and blindsight. Finally, the significance of Freud's unconsciousness in
      the framework of neuroscience was discussed.

PMID- 15580869
TI  - [A case of Addison's disease presented with depression as a first symptom].
AB  - This report describes a 52-year-old male patient with idiopathic Addison's
      disease presenting depression as a first symptom. His psychomotor inhibition,
      depressive mood, sleep disturbances, general fatigue, muscular pain, and
      arthralgia were considered to be due to intense work in a stressful environment.
      Neither his physician nor his orthopedist found any physical disease. Therefore,
      he was diagnosed with endogenous depression by a psychiatric clinic, and
      antidepressants were prescribed. Antidepressants were not sufficient for
      improving his symptoms, and he was admitted to our hospital. Endocrine blood
      examination revealed primary adrenocortical insufficiency. Treatment with
      glucocorticoid induced rapid improvement in both the psychiatric and physical
      symptoms. It is well known that psychiatric symptoms occur in the progressive
      stage of Addison's disease. At present, however, the occurrence of psychiatric
      symptoms is very rare, mainly because of a decrease in the incidence of this
      disease or an increase in mild cases. In addition, Addison's disease presenting
      with psychiatric features in the early stage has the tendency to be overlooked
      and misdiagnosed. Thus, we suggest the necessity of blood work for ACTH and
      cortisol in the field of psychiatry.

PMID- 15580870
TI  - [The past and future of psychiatry and mental treatment in Japan from the
      viewpoint of dynamic psychiatry].
AB  - Many psychoanalytic papers of S. Freud have been introduced in this country since
      the 1910s. However, a majority of psychiatric professors were critical of them.
      K. Marui was an exception. H. Kosawa, as a student of Marui, had studied with R.
      Sterba and P. Federn under the direction of S. Freud in Vienna. After WWII,
      interest in psychoanalysis increased in this country. The Japan Psychoanalytical
      Society and the Japan Psychoanalytical Association were organized in 1955. Also,
      international exchanges in this area have been developing. The psychotherapeutic
      and psychoanalytical needs of individuals in Japan have been increasing in
      relation to social and cultural changes. For the further development of dynamic
      psychiatry, some tasks are considered necessary, as follows: 1) collaboration
      with biological psychiatry, 2) contribution to psychiatric diagnosis, and 3)
      utilization of the therapist-patient relationship in psychiatric treatment.

PMID- 15580871
TI  - [The past and future of psychiatry and mental treatment in Japan from the
      standpoint of biological psychiatry].
AB  - The history of academic meetings, research institutes, and governmental or
      private grants, as well as physiological, biochemical, pharmacological,
      histostructural, brain imaging, animal model, and molecular genetic studies
      related to biological psychiatry in Japan were reviewed. We expect to be able to
      elucidate individually different factors related to an attack of illness or
      relapse. In the treatment of functional mental disorders, future development
      depends on new drug creations that do not have any side effects or drug
      dependence characteristics. Special attention should be paid to new anti
      depressants or anti-anxiety drugs that have prompt euphoric effects. Instruments
      attached to a patient should be as small as possible to avoid psychological
      stress, and a telemetry feature is desirable to enable recording even during an
      acute severe stage of behavior disorder. To avoid fixation to the present
      treatment manual based on EBM (evidence-based medicine), new hypotheses should be
      investigated. I suggest my own plan in this speech.

PMID- 15580872
TI  - [The past and future of psychiatry and mental treatment in Japan from the
      standpoint of clinical psychiatry].
AB  - In the early 1950s, there was a serious shortage of hospital beds for mentally
      ill subjects in Japan, i.e., 30,000 in number as compared to 570,000 in the USA.
      Plans to supply sufficient beds achieved the goal of providing 280,000 beds in
      1975. There were, however, a number of hospitals that fell short of medical and
      ethical standards, and invited severe criticism. To reconcile the situation, new
      laws and regulations were introduced to promote many projects for treating
      patients in the community through social welfare service. Day care institutions
      and outpatient mental clinics have increased markedly in recent years.
      Therapeutic measures for mental patients have changed dramatically in the last
      half of the 20th century, since the discovery of the anti-psychotic effect of
      chlorpromazine. A great number of psychotropic drugs, some produced in Japan,
      have been used routinely in psychiatric practice. In the same period of time,
      many kinds of psychotherapies, some originating in Japan such as the Morita and
      naikan therapies, have been developed for the relief of various psychological
      distresses. The diagnosis and classification of mental illnesses have long
      suffered from uncertainty and discrepancy, even among eminent psychiatrists. The
      publication of DSM-III in 1980, followed by DSM-III-R and IV and ICD-10, provided
      professional staff with practical manuals for making diagnoses of mental
      disorders, and for classifying them using common technical terms. These
      diagnostic criteria contributed greatly to the development of clinical and basic
      research in psychiatry. However, it should be noted that no manuals can replace
      textbooks and writings made available by elaborate studies.

PMID- 15580873
TI  - [Outline of surveys for service needs for social rehabilitation of mentally
      disabled and related matters].

PMID- 15580874
TI  - [Current status and the future of psychiatric care in Japan judged by the results
      of the survey on service needs].

PMID- 15580875
TI  - [The ideal status of psychiatric bed facilities and social rehabilitation
      services projected from the results of surveys on health service needs].

PMID- 15580876
TI  - [Development of community mental health services].

PMID- 15580878
TI  - [Etiology and the development of physiopathology in mental disorders (prevention
      and treatment of the disorders)].

PMID- 15580877
TI  - [Functional stratification of the beds dedicated for psychiatric patients].

PMID- 15580879
TI  - [Objective diagnosis of schizophrenia and its biological basis].

PMID- 15580880
TI  - [Generation of physiopathology of schizophrenia--a hypothesis of temporal-frontal
      lobe 2-step development].

PMID- 15580881
TI  - [Systemic lupus erythematodes. Main symptoms: fatigue, arthralgias, butterfly
      erythemas].

PMID- 15580882
TI  - [Erythropoietin and intravenous iron to save blood in surgery].
AB  - Recombinant human erythropoietin (rHuEPO) and intravenous (i.v.) iron
      administration may be useful tools to save blood in surgery. In the perioperative
      period, rHuEPO should be used in slightly anemic patients for whom an autologous
      predonation program is not recommended (or feasible). In such cases, i.v. iron is
      only given if there is a functional or real iron deficiency state. In the post
      operative period, i.v. iron is administered in association with rHuEPO in an
      attempt to rapidly correct severe post-operative anemia. The same regimen is used
      for patients undergoing surgery for inflammatory bowel disease and rheumatoid
      arthritis. Finally, other particular categories of patients, such as those with
      reduced body weight (< 50 kg), candidates for surgery with increased blood needs
      (> 5 units), or those with a too-short period of time before surgery, also
      benefit from the administration of these two drugs.

PMID- 15580883
TI  - [Low HDL-cholesterol, high triglycerides--well known but often ignored].
AB  - A reduced HDL-Cholersterol and increased triglyzerides are an often seen
      laboratory abnormality. They are known risk factors for arteriosclerosis. However
      the small influence of a pharamcologic treatment on the two reduced the interest
      in them. We therefore want to show the relation of the triglyzerides with the HDL
      Cholesterol and the nonpharmacologic treatment of these two factors. Some
      clinical examples are illustrating the topic.

PMID- 15580884
TI  - [Informed consent and quality management in neurosurgery].

PMID- 15580885
TI  - [Dyspnea and hemoptysis in a young woman with unclear renal alterations].
AB  - We describe the clinical course and treatment of a young woman diagnosed with
      tuberous sclerosis. Classical as well as atypical clinical findings are discussed
      with regards to the differential diagnosis. The most important components of the
      pathogenesis and the criteria necessary for diagnosis are highlighted. In
      addition the similarities and differences to lymphangioleiomyomatosis are
      discussed.

PMID- 15580886
TI  - [Arm swelling and local skin reaction after Di-Te vaccination. 2 case reports].

PMID- 15580887
TI  - [Antiallergic agents from the chickweed].

PMID- 15580888
TI  - Number of geriatric patients grows: you must prepare for distinct challenges.
AB  - With the elder population steadily growing, it's time to reassess how your
      department treats patients beyond age 65. Symptoms are less obvious in
      geriatrics, so more testing often is required. Social situation and daily life
      activity skills are as important as the patient's medical condition. Expand your
      definition of "pain" to include discomfort, anxiety, and depression.

PMID- 15580889
TI  - Rapid-cycle testing cuts bed turnaround by 85%.
AB  - You can use rapid-cycle testing to try out new approaches to overcrowding much
      more frequently than with more traditional process improvement strategies.
      Improving bed turnaround notification can yield dramatic improvements. Telling
      staff they have to try a new process only for three days makes it easier to gain
      buy-in. Look for old policies that are no longer needed, yet continue to keep
      your staff bogged down.

PMID- 15580890
TI  - Care management unit has broad LOS impact.
AB  - A care management unit can dramatically increase bed availability. Consulting
      with internal medicine and the financial department can help identify key sources
      of bottlenecks. Creative use of existing beds can make space available for a new
      unit. Case managers can arrange primary care physician follow-up and track
      ongoing patient compliance after discharge.

PMID- 15580892
TI  - Incentives are a growing trend in emergency department pay, link seen to pay for
      performance.

PMID- 15580891
TI  - Focus on process slashes average cycle time by 37%.
AB  - Don't assume you know the cause of your overcrowding. Examine the data first. Six
      Sigma approach helps staff keep their eyes on the process and ultimately leads to
      the root cause of your problem. Adding more staff may not improve your
      overcrowding problems at all. Breaking down the process into smaller buckets
      makes it easier to problem solve.

PMID- 15580894
TI  - Ensure compliance with environment of care.

PMID- 15580893
TI  - Are you ready for an influx of SARS patients?
AB  - Under a new accreditation standard, EDs and all departments must be prepared to
      handle an influx, or the risk of an influx, of infectious patients. Collaborate
      with your infection control committee, disaster management committee, local board
      of health, and other providers to develop protocols and policies. Hold disaster
      drills in which you must handle infectious patients. ED staff, particularly the
      triage nurses, need training in early recognition of presenting symptoms of
      infectious diseases.

PMID- 15580895
TI  - [The importance of chronic obstructive pulmonary disease].
AB  - COPD mortality is a world-wide growing problem. COPD is the fifth leading cause
      of mortality among all diseases now and is projected to be the third one in 2020.
      In the USA died 119,000 inhabitants in 2001. The Czech republic mortality for
      COPD in the same year was: men 21.3/100,000 inhabitants, women 11.6/100,000; this
      represents total number of 1666 deaths for COPD. Prevalence of COPD is from 4.5%
      to 11% in developed countries of Europe and in the USA; prevalence in the Czech
      republic is 7.7%. Total economic cost of COPD reaches in the USA nearly the same
      value as cost of lung cancer. The cost is increasing with severity of the disease
      and with hospitalization, intensive care unit treatment especially. The average
      length of hospitalization for COPD is in the USA 6.9 days, in Italy 10.6 days, in
      the Czech republic 15.8 days. Increasing lost of life years by premature death
      and inability to work (Disability-Adjusted Life Year--DALY system) in developed
      countries moves COPD from current 12th positron to the 5th one. Quality of life
      of COPD patients is decreased mainly in domain of physical activity in subjects
      with respiratory insufficiency on home long term oxygen therapy.

PMID- 15580896
TI  - [New and old definitions and COPD terminology].
AB  - Terminology of the disease currently known as chronic obstructive pulmonary
      disease has gone through a long and non-uniform development. Various definitions
      have been gradually developed and chronic bronchitis was separated from pulmonary
      emphysema. Various umbrella names have been suggested to unite this group of
      diseases. At present a classification based on World strategy for diagnosing,
      treatment and prevention of the chronic obstructive pulmonary disease from 2000
      which has been published in our country too is used.

PMID- 15580897
TI  - [Pathogenesis of the chronic obstructive pulmonary disease (COPD)].
AB  - An inflammation in the bronchial wall is usually present already in an early
      stage of the disease. An inflammatory infiltration cause predominantly
      mononuclear cells in the mucous membrane and neutrophiles in the phlegm produced
      by airways. Also eosinophiles can participate in the inflammation. Lymphocytes
      distribution is different from asthma because there is mainly submucosa
      infiltrated in COPD. Metaplasia of goblet cells appears. Chronic bronchial
      obstruction characterizing COPD is induced by conjunction of small airways
      disease (obstructive bronchiolitis) and a destruction of pulmonary parenchyma
      (emphysema) which both contribute to an impairment and differ form person to
      person. Chronic inflammation is a cause of remodeling and narrowing of small
      airways. Destruction of pulmonary parenchyma and the inflammation cause loss of
      alveolar connection with small airways and elastic pulmonary stress decreases.
      Two theories try to explain COPD--a theory of imbalance between proteinases and
      antiproteinases and a theory of oxidation stress.

PMID- 15580898
TI  - [Diagnostics and differential diagnostics of the chronic obstructive pulmonary
      disease].
AB  - The author builds upon present definition of chronic obstructive pulmonary
      disease (COPD) and states that diagnosis of COPD is based on history of risk
      factors and on presence of bronchial obstruction which is not entirely
      reversible. The main examination method for diagnosing and confirmation of COPD
      is spirometry. Differential diagnostics is necessary for identifying other
      diseases with similar symptoms: bronchial asthma, congestive heart failure, lung
      carcinoma, bronchiectasia, pulmonary tuberculosis, bronchitis obliterans,
      interstitial pulmonary processes. The author presents a list of symptoms and
      findings which help to distinguish these diseases from COPD.

PMID- 15580899
TI  - [Implication of the lung function tests in chronic obstructive pulmonary
      disease].
AB  - The authors summarize the methods of lung function tests with play important role
      in diagnosis and monitoring the patients with chronic obstructive pulmonary
      disease.

PMID- 15580900
TI  - [Treatment of stabilized chronic obstructive pulmonary disease].
AB  - Treatment of stabilized chronic obstructive pulmonary disease (COPD) is intended
      to decrease consequences activated by causes, such as inhalation of deleterious
      particles and gases especially from polluted air and cigarette smoking. From this
      reason treatment must include an effort to eliminate the cause. Respective
      treatment includes drug administration, rehabilitation, long term oxygen therapy
      in home environment, noninvasive positive pressure ventilation (NIPPV), and
      sometimes surgical procedures. Every treatment should be accompanied with an
      education of a patient and people in his/her surrounding.

PMID- 15580901
TI  - [Treatment principle of the chronic obstructive pulmonary disease (COPD)
      exacerbation].
AB  - COPD is often accompanied with acute symptoms exacerbations. Patients in Ist
      stage: slide grade of COPD and IInd stage: middle grade of COPD suffer
      exacerbations accompanied with increased dyspnoea often together with increased
      cough and increased production of sputum. Patients in IIIrd stage (serious) and
      IVth stage (very serious) experience during exacerbations development of
      respiration insufficiency or its worsening and thus are usually treated in
      hospital. The most frequent causes of exacerbations are tracheobronchial tree
      infections and air pollution. The cause of approximately one third of serious
      exacerbations is not disclosed. Conditions which can resemble acute exacerbation
      are pneumonia, congestive heart failure, pneumothorax, pleural exudation,
      pulmonary embolism, and arrhythmia. Exacerbation treatment is symptomatic.
      Obstruction symptoms are treated with bronchodilatants and corticosteroids
      administration, hypoxemia with oxygen administration and signs of bacterial
      infection with antibiotics.

PMID- 15580902
TI  - [Erythrocytapheresis in patients with secondary polyglobulia].
AB  - Apheresis is in blood components separators used to remove abundant or
      pathological blood components or to replace them with healthy ones.
      Erythrocytapheresis is an up-to-date, efficient and selective alternative of
      venepuncture. In our country it is used especially for treatment of abundant
      erythrocytes in polycythemia vera and secondary polyglobulias where its correct
      use leads both to significant symptomatic relief and erosion of pathogenetic
      chain and to a reduction of over-production of erythrocytes.

PMID- 15580903
TI  - [Pathophysiology and classification of pulmonary hypertension].
AB  - Pulmonary hypertension is present when the mean pulmonary pressure is increased
      above 25 mm Hg in a rest or above 30 mm Hg during exercise. It is possible to
      divide it from different point of view. Well known is pathophysiologic
      classification and Venice classification suggested by WHO symposium 2003. The
      rise of arterial pulmonary pressure is caused by three essential abnormalities,
      these are elevated pulmonary vascular resistance, blood flow and pulmonary artery
      wedge pressure. Vasoconstriction, remodeling of vessels and in situ trombosis are
      pathogenetic mechanism which contribute to rise of pulmonary hypertension.

PMID- 15580904
TI  - [Present ways of diagnosing and treatment of pulmonary hypertension in the Czech
      Republic].
AB  - Pulmonary hypertension is a condition characterized by elevation of the mean
      blood pressure in pulmonary artery above 25 mm Hg at rest or above 30 mm Hg
      during exercise. Pulmonary hypertension signs are not specific. They are
      frequently camouflaged by signs of a primary disease causing pulmonary
      hypertension. That causes difficulties with diagnosing and often doesn't lead to
      recognition of pulmonary hypertension till pressure in pulmonary artery is
      difficult to manage therapeutically. Treatment of secondary pulmonary
      hypertension tries to affect primary disease. In patients with pulmonary artery
      hypertension with preserved vasoreactivity so called conventional treatment is
      still recommended (vasodilatation treatment with calcium channels blockers,
      anticoagulation, oxygentherapy, treatment of heart failure). New ways of
      pharmacotherapy represent administration of prostacyclin, antagonists of
      endothelin receptors, and phosphodiesterase inhibitors. Nonpharmacology treatment
      of pulmonary hypertension includes balloon atrial septostomy, lung
      transplantation, and in chronic thromboembolic pulmonary hypertension pulmonary
      endarterectomy. Current recommendations for pulmonary hypertension treatment
      concentrate especially on patients in functional classes NYHA III and IV. In less
      symptomatic patients there is usually lack of unambiguous clinical data needed
      for treatment. Owning to seriousness of the disease, its difficult diagnosing and
      frequently difficult treatment the global trend is to concentrate care of
      patients with pulmonary hypertension in specialised centers. This problem
      systematically addresses a center at the 2nd Clinic of Internal Medicine of the
      1st Medical Faculty of the Charles University and the General Teaching Hospital
      in Prague in close cooperation with the Clinic of Cardiovascular Surgery at the
      General Teaching Hospital in Prague, and the transplantation center at the 3rd
      Surgical Clinic of the Teaching Hospital Motol in Prague, the Czech Republic.

PMID- 15580905
TI  - [Lung transplantation for primary pulmonary hypertension].
AB  - Significant advances in the treatment of primary pulmonary hypertension (PPH)
      have been achieved in the past decade. Continuous intravenous prostacyclin and
      lung transplantation are complex and effective approaches in the therapy of PPH.
      Indication, technique, postoperative care and results of lung transplantation for
      PPH are discussed.

PMID- 15580906
TI  - [Recommendations for diagnostics and treatment of pulmonary arterial hypertension
      in the Czech Republic].

PMID- 15580907
TI  - [Recommendations for diagnostics and treatment of arterial hypertension--version
      2004. Recommendations of the Czech Society for Prevention of Hypertension].

PMID- 15580909
TI  - Herpes simplex uveitis.
AB  - BACKGROUND: Uveitis in herpes simplex virus (HSV) ocular disease is usually
      associated with corneal stromal disease. It has generally been believed that
      herpetic uveitis in the absence of corneal disease is very rare. When seen it is
      usually attributed to varicella zoster virus (VZV) infections. The diagnosis of
      uveitis caused by herpes simplex is often not diagnosed resulting in inadequate
      treatment and a poor visual result. METHODS: Seven patients from a large uveitis
      practice who presented with a clinical picture of: anterior uveitis and sectoral
      iris atrophy without keratitis, a syndrome highly suggestive of herpetic
      infection, are reported. Polymerase chain reaction (PCR) was done in the aqueous
      of four of them and was positive for HSV. One patient had bilateral disease. Most
      of the patients also had severe secondary glaucoma. RESULTS: Of the seven
      patients presented five had no history of any previous corneal disease. Two had a
      history of previous dendritic keratitis which was not active at the time of
      uveitis development. One patient with bilateral disease was immunosuppressed at
      the time when the uveitis developed. Six of the seven patients had elevated
      intraocular pressures at the time of uveitis and five required glaucoma surgery.
      Intractable glaucoma developed in two patients leading to rapid and severe visual
      loss despite aggressive management. CONCLUSION: Findings suggest that uveitis
      without corneal involvement may be a more frequent manifestation of ocular herpes
      simplex disease than previously thought. Absence of corneal involvement delays a
      correct diagnosis and may worsen visual outcome. Primary herpetic uveitis (when
      there is no history of previous corneal disease) seems to be more severe than the
      uveitis in patients with previous corneal recurrences. The associated glaucoma
      may be a devastating complication.

PMID- 15580910
TI  - Color vision in patients with the Hermansky-Pudlak syndrome.
AB  - PURPOSE: To study color vision in patients with oculocutaneous albinism (OCA)
      METHODS: We evaluated color vision in 42 patients with OCA using the HRR color
      plates. Sixty seven percent of the patients had the Hermansky-Pudlak syndrome
      (HPS), diagnosed genetically or clinically. The remaining patients had unknown
      mutations leading to OCA. RESULTS: 47.6 % of patients of OCA of all types
      included had a color vision defect. Of these, 55% were female and 45% were male
      patients. 50% of patients with the HPS (all types) had a color vision deficit.
      42.9% of patients with OCA of unknown type had color weakness. 57.1% had normal
      color vision. CONCLUSIONS: Results suggest that many patients with OCA and the
      HPS have a mild red-green color perception deficiency that is not a sex linked
      trait. The prevalence of color vision deficits in our study population increased
      with decreasing visual acuity.

PMID- 15580911
TI  - New options in the treatment of diabetic macular edema.

PMID- 15580912
TI  - Keratoconus in Puerto Rico.

PMID- 15580913
TI  - Intraoperative application of topical mitomycin C 0.05% for pterygium surgery.
AB  - BACKGROUND: Pterygium recurrence is a common problem encountered by ophthalmic
      surgeons. Several methods have been suggested to avoid these recurrences. We
      studied the recurrence rate of pterygium after administration of a single
      intraoperative dosage of topical mitomycin C 0.05%. METHODS: A retrospective
      analysis of fifty eyes in forty-nine patients who underwent pterygium excision by
      the same surgeon using intraoperative topical mitomycin C during the years 2002-
      2003. Mitomycin concentration was 0.05% applied to pterygium and adjacent areas
      after undermining and separation from sclera but prior to excision for three
      minutes. Postoperative follow up time was 12 months. RESULTS: The pterygium
      recurred in 4 (8%) eyes. Another four eyes (8%) had a cosmetically acceptable
      recurrence of < 2.0 mm. The only complication was a corneal dellen in one eye.
      CONCLUSION: Intraoperative administration of mitomycin C at 0.05% is safe and
      effective in preventing pterygium recurrences.

PMID- 15580914
TI  - Factors leading to the Computer Vision Syndrome: an issue at the contemporary
      workplace.
AB  - INTRODUCTION: Vision and eye related problems are common among computer users,
      and have been collectively called the Computer Vision Syndrome (CVS). METHODS: An
      observational study in order to identify the risk factors leading to the CVS was
      done. Twenty-eight participants answered a validated questionnaire, and had their
      workstations examined. The questionnaire evaluated personal, environmental,
      ergonomic factors, and physiologic response of computer users. The distance from
      the eye to the computers' monitor (A), the computers' monitor height (B), and
      visual axis height (C) were measured. The difference between B and C was
      calculated and labeled as D. Angles of gaze to the computer monitor were
      calculated using the formula: angle=tan(-1)(D/ A). Angles were divided into two
      groups: participants with angles of gaze ranging from 0 degrees to 13.9 degrees
      were included in Group 1; and participants gazing at angles larger than 14
      degrees were included in Group 2. Statistical analysis of the evaluated variables
      was made. RESULTS: Computer users in both groups used more tear supplements (as
      part of the syndrome) than expected. This association was statistically
      significant (p<0.10). Participants in Group 1 reported more pain than
      participants in Group 2. Associations between the CVS and other personal or
      ergonomic variables were not statistically significant. CONCLUSIONS: Our findings
      show that most important factor leading to the syndrome is the angle of gaze at
      the computer monitor. Pain in computer users is diminished when gazing downwards
      at angles of 14 degrees or more. The CVS remains an under estimated and poorly
      understood issue at the workplace. The general public, health professionals, the
      government, and private industries need to be educated about the CVS.

PMID- 15580915
TI  - [Ophthalmology in Puerto Rico---historical notes].

PMID- 15580916
TI  - [Dr. Jose Maria Vargas].

PMID- 15580917
TI  - Damage control in rheumatoid arthritis. Hard-hitting, early treatment is crucial
      to curbing joint destruction.
AB  - Right from the onset, rheumatoid arthritis is an aggressive disease that can
      quickly alter joint structure and integrity. Such rapid pathogenesis requires
      that the diagnosis be established early and aggressive therapy initiated swiftly.
      In this article, Drs Issa and Ruderman describe what is known about the cause,
      progression, and outcomes of rheumatoid arthritis. They review the steps toward
      its diagnosis and urge that treatment be started promptly--to both contain
      disease and reduce joint destruction as soon as possible.

PMID- 15580918
TI  - Treatment update on spondyloarthropathy. From NSAIDs and DMARDs to anti-TNF-alpha
      agents.
AB  - Traditionally, nonsteroidal anti-inflammatory drugs (NSAIDs) and disease
      modifying antirheumatic agents (DMARDs) have been used to control the symptoms of
      spondyloarthropathy. With the advent of anti-tumor necrosis factor alpha (anti
      TNF-alpha) agents, however, it is now possible to slow disease progression,
      improve overall function, and provide symptomatic relief of arthritis, skin
      lesions, and bowel inflammation associated with these disorders. Here, Drs
      Anandarajah and Ritchlin explore the effectiveness of conventional therapies as
      well as biologic agents that are currently available or under development.

PMID- 15580919
TI  - Raising expectations for arthritis treatment. Biologic response modifiers are
      making remission possible.

PMID- 15580920
TI  - Bilateral eye tumors of long duration. Dermolipoma.

PMID- 15580921
TI  - Skin cancer screening guidelines for older patients?

PMID- 15580922
TI  - Intravascular catheter-related infections. Strategies for combating this common
      foe.
AB  - The introduction and subsequent widespread use of intravenous catheters have
      presented physicians a double-edged sword. Although safe and stable vascular
      access has become essential to modern medical practice, bloodstream infection
      involving these catheters (particularly central venous catheters [CVCs]) is a
      major cause of morbidity and mortality in the United States. In this
      comprehensive review, the author discusses the most common sources of catheter
      related infections, current diagnostic and treatment methods, and graded evidence
      based recommendations for prevention of these infections.

PMID- 15580923
TI  - Patient notes: Chlamydia.

PMID- 15580924
TI  - Atmospheric organic aerosol production by heterogeneous acid-catalyzed reactions.
AB  - Exploratory evidence from our laboratories shows that acidic surfaces on
      atmospheric aerosols lead to very real and potentially multifold increases in
      secondary organic aerosol (SOA) mass and build-up of stabilized nonvolatile
      organic matter as particles age. One possible explanation for these heterogeneous
      processes are the acid-catalyzed (e.g., H2SO4 and HNO3) reactions of atmospheric
      multifunctional organic species (e.g., multifunctional carbonyl compounds) that
      are accommodated onto the particle phase from the gas phase. Volatile organic
      hydrocarbons (VOCs) from biogenic sources (e.g., terpenoids) and anthropogenic
      sources (aromatics) are significant precursors for multifunctional organic
      species. The sulfur content of fossil fuels, which is released into the
      atmosphere as SO2, results in the formation of secondary inorganic acidic
      aerosols or indigenous acidic soot particles (e.g., diesel soot). The
      predominance of SOAs contributing to PM2.5 (particulate matter, that is, 2.5
      microm or smaller than 2.5 microm), and the prevalence of sulfur in fossil fuels
      suggests that interactions between these sources could be considerable. This
      study outlines a systematic approach for exploring the fundamental chemistry of
      these particle-phase heterogeneous reactions. If acid-catalyzed heterogeneous
      reactions of SOA products are included in next-generation models, the predicted
      SOA formation will be much greater and have a much larger impact on climate
      forcing effects than we now predict. The combined study of both organic and
      inorganic acids will also enable greater understanding of the adverse health
      effects in biological pulmonary organs exposed to particles.

PMID- 15580925
TI  - Photochemistry of molecules relevant to the atmosphere: photodissociation of
      nitric acid in the gas phase.
AB  - This Minireview gives an account of the photochemical decay of nitric acid HNO3
      in the gas phase, which has been well investigated under bulk and molecular-beam
      conditions. Due to the importance of this molecule in atmospheric chemistry,
      attention was paid to the irradiation regions around 300 and 200 nm, where solar
      photolysis of HNO3 is expected to be particularly efficient. While the low-energy
      region is characterized by the products OH and NO2, the high-energy region gives
      rise to a variety of photochemical decay pathways, dominated by channels which
      lead to the products HONO + O in different electronic states.

PMID- 15580926
TI  - Extraction of kinetic information from single-molecule experiments.
AB  - We discuss two possible approaches for extracting kinetic information from single
      molecule experiments. The first approach is based on computing correlation
      functions from measured fluorescence signals, and the second on studying the
      statistics of on and off times of the same fluorescence signal. We show that in
      both cases it is possible to extract kinetic information about the nature of
      intramolecular fluctuations of the single molecule. We show that for single
      molecule kinetics the intramolecular fluctuations produce stochastic memory
      effects which lead to new dynamic features that do not exist in traditional
      chemical kinetics. In particular, we investigate a new type of chemical
      oscillations in correlation functions observed experimentally by Edman and Rigler
      (Proc. Natl. Acad. Sci. USA 2000, 97, 8266).

PMID- 15580927
TI  - Infrared absorption features of gaseous isopropyl carbocations.
AB  - C3H7+ ions were formed in the cell of a Fourier transform ion cyclotron resonance
      mass spectrometer and assayed by their multi-photon dissociation (MPD) behavior,
      triggered by the absorption of tunable IR radiation from a free-electron laser
      source providing a high fluence. The derived experimental IRMPD spectrum, which
      reflects the active vibrational modes of the ion, was compared with the IR
      spectra calculated for the optimized structures of the most-stable species on the
      C3H7+ potential energy surface, namely, a chiral iC3H7+ ion of C2 symmetry and an
      asymmetric corner-protonated cyclopropane, cC3H7+. The significant features in
      the IRMPD spectra of both the unlabeled and the perdeuterated ions obtained by
      ionization and fragmentation of isobutane or 2-chloro[D7]propane confirm the
      presence of the isopropyl cation, the ground-state isomer, whose IR spectroscopic
      features can thus be comparatively checked in the gas phase and in condensed
      superacid media. Details of the IRMPD features are suggested to result from the
      nearly barrierless interconversion of the two C2 enantiomers.

PMID- 15580928
TI  - Torsional barriers in aromatic molecular clusters as probe of the electronic
      properties of the chromophore.
AB  - We present a computer program that is capable of fitting n-fold torsional
      barriers Vn (n = 2-6) and torsional constants F simultaneously to high- and low
      resolution spectroscopic data of different isotopomeric internal rotors. The
      program has been utilized to fit independently barriers and torsional constants
      for both electronic states of several aromatic clusters. The constant F of the
      ammonia moiety in the phenol-ammonia cluster is shown to decrease upon electronic
      excitation, thus imaging the formation of a hydrogen-bonded complex between the
      phenoxy radical and the NH4 radical in the excited state. In contrast, for the
      naphthol-ammonia 1:1 clusters no change of F of ammonia could be found. For
      phenol-methanol cluster we found a decrease of F upon excitation which points to
      a stronger hydrogen bond between phenol and methanol in the excited state. A
      strong reduction of the torsional barrier upon excitation points to the formation
      of a methoxonium radical in a similar photoreaction as in phenol-ammonia cluster.
      For the phenol-water system we postulate the same mechanism, a photoreaction,
      which leads to a translocated hydrogen atom in the S1 state what can be deduced
      from the change of the torsional constant upon electronic excitation.

PMID- 15580929
TI  - Spectroscopic properties of trapped electrons on the surface of MgO
      nanoparticles.
AB  - To characterise electron-trapping sites on the surface of MgO nanoparticles,
      surface colour centres were generated using UV light in conjunction with selected
      hydrogen-based electron sources. Four different colour-centre species, including
      the characteristic (e-)(H+) or F(S)+(H) centre, were identified due to the
      distinct shape of the respective electron paramagnetic resonance (EPR) signals.
      The analysis of the EPR saturation behaviour down to microwave powers of 5 x 10(
      3) mW reveals an enhanced spin-relaxation probability of the (e-)(H+) centre
      compared to all other F(S)+ centres that do not exhibit significant magnetic
      interactions with hydroxylic protons. Beside the dipolar magnetic interaction in
      the (e-)(H+) centre observed by EPR, the electronic interaction between the
      unpaired electron and the proton of a closely spaced OH group produces a redshift
      of the OH stretching band by about 70 to 170 cm(-1), as observed by infrared
      spectroscopy. EPR and IR spectroscopic data obtained after the selective address
      of individual reaction channels for surface colour-centre formation point to the
      fact that (e-)(H+) centres are formed by trapping electrons from H atoms.
      Consequently, the underlying surface defect does not belong to the sites of the
      MgO surface, which chemisorb hydrogen via a heterolytic splitting process.

PMID- 15580930
TI  - Singlet excited-state interactions in naphthalene-thymine dyads.
AB  - Two thymidine-derived nucleosides 1 and 2 were prepared by attaching a chiral
      naphthalene to the positions 5' and 3' of the sugar. The resulting dyads, which
      contain key substructures present in drugs and nucleic acids, exhibit different
      spatial arrangements (transoid or cisoid) of the fluorophore relative to the
      thymine unit. Emission measurements on these compounds in the presence of ROH
      molecules revealed a remarkable intramolecular prescence quenching for dyad 1.
      The obtained results are consistent with quenching of the singlet excited state
      of 1 by hydrogen-bond donor solvents. Thus, a physical deactivation process
      (vibronically induced internal conversion) would be the pathway responsible for
      the accelerated decay of 1*, favorably competing with fluorescence and
      intersystem crossing to the triplet. This effect appears to be strongly dependent
      on the relative spatial arrangement between the naphthalene and thymine units,
      together with the hydrogen-bonding ability of the employed ROH.

PMID- 15580931
TI  - Ligand dynamics in myoglobin: calculation of infrared spectra for
      photodissociated NO.
AB  - We present molecular dynamics simulations of the photodissociated state of MbNO
      performed at 300 K using a fluctuating charge model for the nitric oxide (NO)
      ligand. After dissociation, NO is observed to remain mainly in the centre of the
      distal haem pocket, although some movement towards the primary docking site and
      the xenon-4 pocket can be seen. We calculate the NO infrared spectrum for the
      photodissociated ligand within the haem pocket and find a narrow peak in the
      range 1915-1922 cm(-1). The resulting blue shift of 1 to 8 cm(-1) compared to gas
      phase NO is much smaller than the red shifts calculated and observed for carbon
      monoxide (CO) in Mb. A small splitting, due to NO in the xenon-4 pocket, is also
      observed. At lower temperatures, the spectra and conformational space explored by
      the ligand remain largely unchanged, but the electrostatic interactions with
      residue His64 become increasingly significant in determining the details of the
      ligand orientation within the distal haem pocket. The investigation of the effect
      of the L29F mutation reveals significant differences between the behaviour of NO
      and that of CO, and suggests a coupling between the ligand and the protein
      dynamics due to the different ligand dipole moments.

PMID- 15580932
TI  - Probing ligand-protein recognition with sum-frequency generation spectroscopy:
      the avidin-biocytin case.
AB  - Infrared/visible sum-frequency generation (SFG) spectroscopy is used to study the
      recognition of a protein (avidin) by a derived vitamin (biocytin) adsorbed on a
      calcium fluoride substrate. The specificity of the process is tested by replacing
      avidin with bovine serum albumin or presaturated avidin. The SFG spectroscopy
      shows drastic modifications in the CH and NH spectral ranges only upon exposure
      of the biocytin film to avidin. The comparison of the SFG data with Fourier
      transform infrared reflection absorption spectra (FT-IRRAS) in the same spectral
      ranges illustrates the advantages of nonlinear spectroscopy for studying and
      detecting recognition between biomolecules.

PMID- 15580933
TI  - Oxygenolysis of flavonoid compounds: DFT description of the mechanism for
      quercetin.
AB  - Flavonoids are naturally occurring phenol derivatives present in substantial
      amounts in a large variety of plants, fruits and vegetables daily eaten by
      humans. Most of these compounds exhibit several interesting biological
      activities, such as antiradical and antioxidant actions. Indeed, by complexation
      with specific enzymes, flavonoids are notably liable to metabolize molecular
      dioxygen. On the basis of experimental results describing oxygenolysis of the
      flavonoid quercetin, activated by the enzyme quercetin 2,3-dioxygenase (2,3
      QD),ur attention has focused on the role of metal center in the activation of the
      substrate quercetin. Thus, in the present study, by means of DFT calculations at
      the B3LYP/ 6-31(+)G* level on model molecular systems, we describe different
      mechanisms for dioxygen metabolization by quercetin. Stationary points are
      described, and energetic and structural analyses along the reaction paths are
      reported. Our calculations show that the copper cation must act as an oxidant
      towards the substrate and that the reaction proceeds through a 1,3-cycloaddition.

PMID- 15580934
TI  - Investigation of redox properties of different PtSn/Al2O3 catalysts.
AB  - Alumina-supported Sn and PtSn particles are studied by 119Sn Mossbauer
      spectroscopy after oxidation and reduction under various conditions. The observed
      species of Sn(IV), Sn(II) and Sn(0) are grouped in several categories, each being
      characterised by distinct structural properties. Tin phases in contact with the
      support or with platinum are identified. The results are used to establish a
      model describing the phase transformations occurring in PtSn particles under
      oxidising or reducing conditions. Particular attention is paid to the
      reduction/reoxidation mechanisms governing H2/O2 double titrations. An increased
      reactivity of tin towards oxygen, induced by the contact with platinum, is
      demonstrated. It is shown that tin contributes to the oxygen uptake VO1 of a
      first titration cycle by platinum-catalysed transformation of Sn(II) into an
      oxometallic phase Pt(x)Sn(O). The oxygen titre VO2 of a second cycle is due to O2
      chemisorption on platinum only.

PMID- 15580935
TI  - Light-scattering study of the aggregation of syndiotactic poly(methyl
      methacrylate) in solution.
AB  - Syndiotactic poly(methyl methacrylate (s-PMMA) may undergo aggregation in n-butyl
      chloride (n-BuCl) at temperatures below the theta temperature. The aggregation
      behavior of the s-PMMA with weight-average molecular weight M(w) =6.06 x 10(5) g
      mol(-1) was studied by a combination of static and dynamic laser-light-scattering
      experiments. A solution of concentration 1.12 x 10(-4) g mL(-1) was quenched from
      50 degrees C (above the theta temperature in n-BuCl, 35 degrees C to 12 degrees
      C, and the aggregation process was measured over 60 h. The time dependence of
      M(w) the root-mean-square z-average radius of gyration < R(g) >, and the average
      hydrodynamic radius <R(h)> were used to monitor the growth of the aggregates,
      with the result M(w) approximately < R(g) > d(f) (where d(f) = 1.98 +/- 0.02),
      which implies the formation of a fractal aggregate. The observed fractal
      dimension, d(f), is close to that expected for a reaction-limited cluster
      aggregation for which d(f) = 2.1. In addition, atomic force microscopy was used
      to image the aggregates.

PMID- 15580936
TI  - Multiple refocusing in NMR spectroscopy: compensation of pulse imperfections by
      scalar couplings.
AB  - When applying multiple refocusing pulses to characterize the cross-correlated
      relaxation of heteronuclear multiple quantum coherence 2NxHx in biomolecules, the
      unavoidable effects of pulse imperfections are compensated by the scalar
      couplings between nitrogen atoms and protons. The experiment, which is useful as
      a tool for studying slow internal dynamics of biomolecules, greatly benefits from
      this compensation. The underlying effect is a manifestation of an interchange
      between three noncommuting components of the density operator. One perturbing
      Hamiltonian is counteracted by another, which leads to a nearly complete
      suppression of the perturbation. The effect proves to be an example of a hitherto
      unknown phenomenon in NMR spectroscopy.

PMID- 15580937
TI  - Structural and magnetic investigations of the mixed-valence Fe(II,III) two
      dimensional layer complex, [Fe2(II) Fe2(III)(HCOO)10(C6H7N)6]n.
AB  - The structure of the complex, [Fe2(II)Fe2(III)(HCOO)10(C6H7N6)n, (1) exhibits a
      neutral two-dimensional layer network of alternating iron(II) and iron(III) ions,
      bridged equatorially by formate groups. All iron atoms are octahedrally
      coordinated, with iron(III) coordinating axially to one gamma-picoline and one
      formate group, while the iron(II) centers interact axially with two gamma
      picoline groups, above and below the layer plane. The complex crystallizes in the
      triclinic space group P1 at all studied temperatures [at 120 K, the cell
      dimensions are: a = 10.228(1), b = 12.071(1), c = 12.072(1) A, alpha = 89.801(2),
      beta = 71.149(2), gamma = 73.371(2) degrees]. An intralayer antiferromagnetic
      exchange interaction of J = -2.8 cm(-1) between iron(II) and iron(III) was
      observed in the magnetic studies. Decreasing the temperature to close to 20 K
      causes a magnetic-ordering phenomenon to occur and a low-temperature phase with a
      long-range antiferromagnetic spin orientation appears. The magnetic phase
      transition was confirmed by Mossbauer spectroscopic studies at temperatures above
      and below the critical temperature. Structural information of 1 from synchrotron
      X-ray diffraction data collected at room temperature and 16 K suggests that the
      antiferromagnetic ordering is caused by an enhanced pi-pi interaction between chi
      picoline groups from adjacent layers.

PMID- 15580938
TI  - Intramolecular charge transfer in pyrromethene laser dyes: photophysical
      behaviour of PM650.
AB  - Absorption and fluorescence (steady-state and time-correlated) techniques are
      used to study the photophysical characteristics of the pyrromethene 650 (PM650)
      dye. The presence of the cyano group at the 8 position considerably shifts the
      absorption and fluorescence bands to lower energies with respect to other related
      pyrromethene dyes; this is attributed to the strong electron-acceptor character
      of the cyano group, as is theoretically confirmed by quantum mechanical methods.
      The fluorescence properties of PM650 are intensively solvent-dependent. The
      fluorescence band is shifted to lower energies in polar/protic solutions, and the
      evolution of the corresponding wavelength with the solvent is analysed by a
      multicomponent linear regression. The fluorescence quantum yield and the lifetime
      strongly decrease in polar/protic solvents, which can be ascribed to an extra
      nonradiative deactivation, via an intramolecular charge-transfer state (ICT
      state), favoured in polar media.

PMID- 15580939
TI  - Molecular complexes of organometallic molecules with noble gases: the rotational
      spectrum of dimethylsilane-argon.
AB  - The rotational spectrum of the molecular complex dimethylsilane-argon was
      investigated by free-jet absorption millimeter-wave and molecular-beam Fourier
      transform spectroscopy. The absolute energy minimum corresponds to a conformation
      in which the argon atom lies in the plane of symmetry of dimethylsilane,
      perpendicular to the C-Si-C plane. The distance of Ar atom is tilted 14 degrees
      away from the Si atom. The zero-point dissociation energy was estimated from the
      centrifugal distortion constant D(J) to be 2.2 kJ mol(-1). Small splitting, due
      to tunneling of the Ar atom and internal rotation of the two methyl groups, was
      observed, measured, and used to determine the potential energy surface for these
      motions.

PMID- 15580940
TI  - Bifurcated CH2 ... O and (C-H)2 ... F-C weak hydrogen bonds: the oxirane
      difluoromethane complex.

PMID- 15580941
TI  - Photon antibunching proves emission from a single subunit in the autofluorescent
      protein DsRed.

PMID- 15580942
TI  - Higher-excited-state photophysical pathways in multichromophoric systems revealed
      by single-molecule fluorescence spectroscopy.

PMID- 15580943
TI  - A numerical evidence for nonframework cation redistribution upon water adsorption
      in faujasite zeolite.

PMID- 15580944
TI  - Chemical derivatisation of multiwalled carbon nanotubes using diazonium salts.

PMID- 15580945
TI  - Equilibria between peroxo and hydroperoxo species in the titanosilicates: an in
      situ high-resolution XANES investigation.

PMID- 15580946
TI  - Assessment of neonatal tetanus elimination in Rwanda.

PMID- 15580947
TI  - United States life tables, 2002.
AB  - This report presents period life tables for the United States based on age
      specific death rates in 2002. Data used to prepare these life tables are 2002
      final mortality statistics; July 1, 2002, population estimates based on the 2000
      decennial census and data from the Medicare program. Presented are complete life
      tables by age, race, and sex. In 2002 the overall expectation of life at birth
      was 77.3 years, representing an increase of 0.1 years from life expectancy in
      2001. Between 2001 and 2002, life expectancy increased for both males and
      females. Life expectancy increased by 0.2 years for black males (from 68.6 to
      68.8). It increased by 0.1 year for white males (from 75.0 to 75.1), for white
      females (from 80.2 to 80.3), and for black females (from 75.5 to 75.6).

PMID- 15580948
TI  - Receiving mass casualties at sea: the capabilities of the primary casualty
      receiving facility.
AB  - Exercise Aurora (May-June 2004) off the eastern seaboard of the United States
      provided an opportunity, on several occasions, to test the ability of the PCRF to
      cope with large numbers of "casualties" arriving simultaneously. This article
      reviews the role of the PCRF, its facilities and capabilities, and how these are
      currently utilised to handle mass casualties. Some of the valuable lessons
      identified from Exercise Aurora are briefly discussed.

PMID- 15580949
TI  - The management of burns on HM ships--a review of burn care provision and special
      factors associated with burns at sea.

PMID- 15580950
TI  - Measurement of carbon dioxide levels during use of ELSA and the effect of venting
      on these levels.
AB  - DESIGN: A prospective, objective assessment of ELSA use, in order to determine
      whether venting of the ELSA influences carbon dioxide (CO2) levels. PRIMARY
      ENDPOINT: Inspired and expired CO2 levels. SETTING: On board RFA ARGUS during
      Operation TELIC. METHODS: 10 volunteers had a baseline of inspired and expired
      CO2 levels taken. These levels were measured at one minute intervals during use
      of an ELSA in 3 conditions--sitting, jogging and jogging with venting. RESULTS:
      There was no difference in expired CO2 levels between baseline and use of ELSA
      whilst sitting. Periodic venting of the ELSA made no difference to inspired and
      expired CO2 levels. CONCLUSIONS: Venting of the ELSA during use makes no
      difference to CO2 levels whether inspired or expired. Therefore, venting is
      unnecessary and potentially wastes vital time during escape from a smoke-filled
      compartment and adds additional stress to the escapee.

PMID- 15580951
TI  - The role of the maxillofacial senior house officer in trauma management.

PMID- 15580952
TI  - Lyme disease--a hazard of an appointment to the United States.
AB  - Lyme disease is just one of the many tick borne diseases to be encountered within
      the United States that can affect humans. To the visitor who confines their time
      to major conurbations the risk of contracting Lyme disease is minimal. However,
      anyone planning a hiking trip during tick season must take precautions to prevent
      being bitten and possibly infected. For those of us who live within an endemic
      area the shower after a days gardening is not just to remove sweat and dirt but
      also an opportunity to check for, and if necessary remove, any ticks that may
      have chosen a human host. Fortunately, the liberal use of insecticide around our
      house combined with one of our cat's single pawed attempt to eliminate the local
      white-footed mouse population appears to have been effective in reducing the tick
      count.

PMID- 15580953
TI  - To transfuse or not to transfuse. The pathophysiology of anaemia.

PMID- 15580955
TI  - Phomol, a new antiinflammatory metabolite from an endophyte of the medicinal
      plant Erythrina crista-galli.
AB  - Phomol (1), a novel antibiotic, was isolated from fermentations of a Phomopsis
      species in the course of a screening of endophytic fungi from the medicinal plant
      Erythrina crista-galli. For this Argentinean leguminosa antiinflammatory and
      neuroleptic activities have been described. The compound exhibits antifungal,
      antibacterial and weak cytotoxic acticity. The antiinflammatory activity was
      tested in different reporter gene assays (TNF-alpha, STAT1/STAT2 and NF-kappaB)
      and in an ear edema model in mice. In the reporter gene assays 1 exhibited no
      activity, whereas 1 showed interesting antiinflammatory activity in the mouse ear
      assay. The compound is a polyketide lactone and its structure was elucidated by
      spectroscopic methods.

PMID- 15580956
TI  - Epohelmins A and B, novel lanosterol synthase inhibitors from a fungal strain FKI
      0929.
AB  - From a fungal strain FKI-0929, two compounds designated epohelmins A and B, were
      isolated as new natural products with inhibitory activity against recombinant
      human lanosterol synthase. The crude extract from the whole broth of this strain
      was fractionated by silica gel column chromatography and HPLC to afford two
      isolated inhibitors. Detailed spectroscopic analyses led to the identification of
      their structures. They are diastereomers of 4,5-epoxy-2-(4'-oxoundec-(5'E)-enyl)
      heptamethylenamines, and their relative stereochemical configurations were
      determined as (2R, 4R, 5R) or (2S, 4S, 5S) for epohelmin A, and (2R, 4S, 5R) or
      (2S, 4R, 5S) for epohelmin B, respectively. These compounds inhibited recombinant
      human lanosterol synthase with IC50 values of 10 and 6.0 microM, respectively.

PMID- 15580957
TI  - YM-193221, a novel antifungal antibiotic produced by Pseudallescheria
      ellipsoidea.
AB  - A novel antifungal antibiotic, YM-193221, was found in the culture broth of a
      fungus, Pseudallescheria ellipsoidea. The structure of the antibiotic was
      determined through several spectroscopic experiments as 2-dimethylamino-1-(4
      hydroxyphenyl)-8,10-dimethyl-6-dodecene-3-one. YM-193221 exhibited potent
      antifungal activity against Candida albicans and also inhibited mannan synthesis
      in the yeast cell wall.

PMID- 15580958
TI  - A new nonadride derivative, dihydroepiheveadride, as characteristic antifungal
      agent against filamentous fungi, isolated from unidentified fungus IFM 52672.
AB  - In the screening of searching for new antifungal agents, a new nonaride compound,
      dihydroepiheveadride (1), was isolated from unidentified fungus IFM 52672 as the
      most potent antifungal principle from this organism. The structure of 1 was
      established on the basis of spectroscopic and chemical investigation, as well as
      detailed comparison of the spectroscopic and physico-chemical data of the
      oxidized derivative (3) from 1 with those of heveadride (2). Compound 1 showed
      strong antifungal activity against various filamentous fungi including human
      pathogens Aspergillus fumigatus, Penicillium marneffei and Trichophyton spp. It
      also showed the growth inhibition activity against certain human pathogenic
      yeasts such as Trichosporon species, while it had weak or no antifungal activity
      against Candida spp. and Cryptococcus neoformans, and no antibacterial activity
      against Bacillus subtilis nor against Escherichia coli. The antifungal potencies
      of compounds 2 and 3 were found to be weaker than that of 1.

PMID- 15580959
TI  - API-mass spectrometry of polyketides. II. Fragmentation analysis of 6
      deoxyerythronolide B analogs.
AB  - The API-MS spectra of 6-deoxyerythronolide B (6-dEB) and a number of its analogs
      have been studied to gain information into the fragmentation patterns of 6
      deoxyerythronolides under atmospheric pressure ionization conditions. The API-MS
      spectrum of 6-dEB shows five major families of fragments. The spectra of a series
      of desmethyl-6-dEBs allow assignment of these fragment families to structural
      subunits as well as provide information regarding the fragmentation mechanisms.
      The spectrum of [9-(18)O]-6-dEB is consistent with loss of the ketone oxygen
      during the first dehydration, and the spectra of other oxygen-modified analogs
      implicate the non-obligate formation of a 5,9-hemiacetal in the initial stages of
      fragmentation. These results taken together are used to propose a model for the
      fragmentation of 6-dEB and its analogs under API conditions.

PMID- 15580960
TI  - Suppressive effect of antibiotic siomycin on antibody production.
AB  - The antibiotic thiazole compound siomycin, which we have found from the culture
      broth of Actinomycetes (strain No.806097) in search of antibody production
      inhibitor, showed the in vitro immunosuppressive property against B-cells
      stimulated with T-cell independent antigen DNP-LPS (dinitrophenyl
      lipopolysaccharide) while it also showed inhibitory effect against T-cell
      proliferation. Its inhibitory mechanism was considered to be different from that
      of FK506, the representative of T-cell immunosuppressant. Moreover, siomycin
      showed inhibitory effect in both T-cell dependent and independent murine antibody
      production models and decreased the severity in murine collagen arthritis model.
      Therefore, siomycin is a unique immunosuppressant which has potential for the
      treatment of some antibody-mediated diseases.

PMID- 15580961
TI  - Two new macrolides produced by Streptomyces sp. CS.

PMID- 15580962
TI  - A new anthracycline antibiotic micromonomycin from Micromonospora sp.

PMID- 15580963
TI  - Cell cycle inhibitory activity of 4-hydroxy-3-(3'-methyl-2'-butenyl)-benzoic acid
      from Curvularia sp. KF119.

PMID- 15580964
TI  - Hybrid analogues of gramicidin S and gratisin.

PMID- 15580965
TI  - Perspectives. Tech coverage: "Show me the money" vs "Show me the value".

PMID- 15580966
TI  - Management of porous polyethylene implant exposure in patients with
      retinoblastoma following enucleation.
AB  - BACKGROUND AND OBJECTIVE: To report the features and the management of porous
      polyethylene implant exposure in patients with retinoblastoma following
      enucleation. PATIENTS AND METHODS: The medical records of 33 patients (33
      sockets) following enucleation and porous polyethylene implantation for
      retinoblastoma were reviewed. RESULTS: The mean age at enucleation was 24 months
      (range, 2 to 85 months). The exposure rate was 33% (11 cases), and the mean time
      from enucleation to exposure was 15 months (range, 7 to 29 months). One case was
      resolved only by supportive management, and the remaining 10 were successfully
      treated with a scleral patch graft and maintained well during a mean follow-up of
      15 months after surgical repair. There was no statistical evidence that age,
      gender, implant size, or chemotherapy had an effect on implant exposure.
      CONCLUSIONS: Porous polyethylene implant exposure does not seem to be resolved by
      conservative management. We recommend early surgical management, such as scleral
      patch graft, as opposed to supportive management.

PMID- 15580967
TI  - Increased intraocular pressure and corneal endothelial cell loss following
      phacoemulsification surgery.
AB  - BACKGROUND AND OBJECTIVE: To compare the influence of low-molecular-weight
      viscoelastics on postoperative intraocular pressure (IOP) and corneal endothelial
      cell loss after phacoemulsification PATIENTS AND METHODS: Sixty-nine eyes
      undergoing phacoemulsification surgery were randomized to have either Opegan
      (Santen Pharmaceuticals, Osaka, Japan) alone or the soft-shell technique using
      Viscoat (Alcon Surgical, Fort Worth, TX) during phacoemulsification. The IOP was
      measured preoperatively and at 5 and 24 hours postoperatively. Intraoperative
      factors and corneal endothelial cell loss were also examined. RESULTS: Mean IOP
      was increased at 5 hours after surgery but returned to preoperative levels at 24
      hours in the Opegan group, whereas it remained higher at 24 hours than at
      preoperative levels in the soft-shell group. When comparing groups, IOP at 5 and
      24 hours postoperatively in the Opegan group was significantly less than that in
      the soft-shell group. Corneal endothelial cell loss was approximately the same in
      the two groups. CONCLUSION: The increase in IOP following phacoemulsification
      surgery with the use of Opegan was less than that with the soft-shell technique
      using Viscoat, although endothelial injury was almost the same.

PMID- 15580968
TI  - Small-incision manual extracapsular cataract extraction using deep-topical, nerve
      block anesthesia.
AB  - BACKGROUND AND OBJECTIVE: To determine whether deep-topical anesthesia is
      suitable for small-incision manual extracapsular cataract extraction (ECCE).
      PATIENTS AND METHODS: Three hundred twenty-six eyes of 253 patients had small
      incision manual ECCE under topical anesthesia with a 4% lidocaine-soaked sponge.
      The severity of the pain, eye movements, blepharospasm, and intraoperative
      complications were recorded. Patient and surgeon satisfaction levels were
      assessed. RESULTS: Operations on 323 eyes (99%) were completed with topical
      anesthesia. Intraoperatively, topical anesthesia was converted to peribulbar
      anesthesia in 3 eyes (0.9%) because of excessive eye movements. The cauterization
      of the scleral vessels and conjunctiva and the subconjunctival injection were the
      stages causing severe pain. The most frequent intraoperative complication was
      posterior capsule rupture in 6 eyes (1.8%). The satisfaction level was 95% for
      the patients and 90% for the surgeon. CONCLUSION: Deep-topical, nerve-block
      anesthesia provides anesthesia with sufficient quality for small-incision manual
      ECCE.

PMID- 15580969
TI  - Releasable suture techniques for trabeculectomy: an illustrative review.

PMID- 15580970
TI  - Cyclosporin-augmented laser peripheral iridoplasty.
AB  - BACKGROUND AND OBJECTIVE: Almost all patients develop iritis following argon
      laser peripheral iridoplasty. Numerous adverse effects, particularly elevated
      intraocular pressure (IOP) and reduced microbial resistance, complicate therapy
      with topical corticosteroids. An immunomodulator, such as cyclosporin A (CsA),
      avoids these undesirable effects, yet may suppress ocular inflammation. MATERIALS
      AND METHODS: Argon laser peripheral iridoplasty was performed on anesthetized
      rabbits with pigmented iris epithelium. Rabbits were randomly assigned to the
      untreated control, CsA (2%), or dexamethasone (0.1%) groups. Postoperative
      inflammation was documented by digital photography, IOP, and protein in aqueous
      humor. RESULTS: Iris injection, aqueous flare, and fibrin decreased most rapidly
      in the control group, as did protein in aqueous humor. Decreases in IOP of 49% to
      58% were similar in all three groups. There were no differences in conjunctival
      congestion between the CONCLUSION: Neither treatment with antiinflammatory drugs
      that inhibit phagocytosis (e.g., topical steroids) nor treatment with anti
      inflammatory drugs that suppress T-lymphocytes (e.g., topical sA) significantly
      attenuated inflammation following iridoplasty.

PMID- 15580971
TI  - In vivo laser and white-light confocal microscopic findings of human conjunctiva.
AB  - BACKGROUND AND OBJECTIVE: To report in vivo laser and white-light confocal
      microscopic findings of human conjunctiva to investigate the potential
      application of these confocal microscopes as diagnostic devices for normal and
      pathologic conjunctiva. PATIENTS AND METHODS: Two healthy volunteers, 28- and 35
      year-old men, participated in this study. The temporal bulbar conjunctiva, which
      was approximately 5 mm away from the limbus, was examined by in vivo laser and
      white-light confocal microscopic analysis. RESULTS: Using laser confocal
      microscopy, at least two different cell types could be distinguished in both
      subjects: conjunctival superficial epithelial cells and conjunctival basal
      epithelial cells. In contrast, conjunctival epithelial cells could not be
      visualized using white-light confocal microscopy. CONCLUSIONS: These results
      indicate that laser confocal microscopy, but not white-light confocal microscopy,
      can be used to visualize in vivo human conjunctiva. Further investigations in a
      large number of normal subjects and in patients with conjunctival pathologies are
      required to fully evaluate the usefulness of this device in daily clinical
      ophthalmology.

PMID- 15580972
TI  - Retinal thickness in normal and RCD1 dogs using optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To compare retinal thickness and retinal nerve fiber
      layer (RNFL) thickness values obtained by optical coherence tomography (OCT) in
      normal dogs and dogs with rod-cone dysplasia type 1 (RCD1). MATERIALS AND
      METHODS: Eight eyes of 6 normal hound-bred dogs and 12 eyes of 6 dogs with RCD1,
      2 to 5 years of age, were examined using the Fast RNFL Thickness, Fast Macular
      Thickness, and line scan protocols of OCT. RESULTS: Retinal thickness was
      significantly higher in the tapetal fundus than in the non-tapetal fundus, in
      both normal (P = .0036) and RCD1 (P < .0001) dogs. Superotemporal, superonasal,
      and inferior retinal thickness values were significantly higher in normal dogs (P
      < .0001). Area centralis thickness was 183.5 +/- 10.66 microm in normal dogs and
      136.16 +/- 13.12 microm in RCD1 dogs (P < .0001). There was no difference in RNFL
      thickness between normal and RCD1 dogs (P > .05). CONCLUSION: OCT scanning in
      dogs is considered to be a useful method of evaluation in future retinal studies
      in this animal model.

PMID- 15580973
TI  - Anhidrotic ectodermal dysplasia with spontaneous corneal perforation and
      keratoconus.
AB  - A patient with anhidrotic ectodermal dysplasia and severe dry eyes was admitted
      with spontaneous corneal perforation in his right eye. The corneal perforation
      was sealed with cyanoacrylate glue and bandage contact lens placement. Three
      weeks later, the patient underwent penetrating keratoplasty. On follow-up
      examination, he had corneal graft abscess that was treated successfully with
      topical antibiotics and corneal erosion that was treated with a bandage contact
      lens. Corneal topography performed as a routine examination showed inferior
      corneal steepening typical of keratoconus in the left eye. This accidental
      discovery of keratoconus in the patient's left eye may suggest a possible
      association between anhidrotic ectodermal dysplasia and keratoconus.

PMID- 15580974
TI  - Late reexposure after upper eyelid tarsoconjunctival flap for exposed porous
      orbital implant.
AB  - The records of four patients with exposed porous orbital implant treated with the
      upper eyelid tarsoconjunctival Hughes flap were reviewed. The tarsoconjunctival
      Hughes flap was fashioned for two patients with recurrent orbital porous implant
      exposure and two patients with primary orbital porous implant exposure (5 to 6 mm
      at largest dimension; mean, 5.6 mm). There were two hydroxyapatite and two high
      density polyethylene implants. In all patients, reexposure (2 to 3 mm at largest
      dimension; mean, 2.5 mm) occurred 6 to 24 weeks (mean, 13 weeks) after the
      tarsoconjunctival Hughes flap procedure at the junction of the flap and the
      socket surface conjunctiva. Mean follow-up duration was 18.7 months (range, 7 to
      27 months). Linear late reexposure is the main drawback of the upper eyelid
      tarsoconjunctival Hughes flap to cover an exposed orbital porous implant.

PMID- 15580975
TI  - Socket infection due to retained gauze after evisceration.
AB  - A 64-year-old man had late-onset socket infection due to retained surgical gauze
      after evisceration. External examination showed a mass of retained surgical gauze
      with copious yellowish discharge and gas bubbles. Computed tomography scans
      showed a 3.2 x 2.4 x 2.4-cm heterogeneous mass and numerous gas bubbles. Culture
      of the discharge yielded Pseudomonas aeruginosa, Streptococcus viridans,
      Peptostreptococcus species, and Fusobacterium species. Surgical debridement and
      antibiotic therapy achieved a rapid resolution. Retained gauze after evisceration
      may lead to socket infection, and such a complication should be avoided.

PMID- 15580976
TI  - Combined cyclectomy-trabeculectomy procedure for refractory glaucoma.
AB  - A new surgical technique for cases of refractory glaucoma is described. The
      technique has been performed on 42 severely glaucomatous eyes. The technique
      consists of a partial excision of the ciliary body combined with a trabeculectomy
      to maintain an effective filtration by several passages. All excised material was
      verified as ciliary body by an ophthalmic pathologist. The follow-up period was 2
      to 5 years. Intraocular pressure decreased after the operation and remained less
      than 20 mm Hg in 39 eyes. The visual acuity increased in 8 of 42 eyes and
      remained the same in 32 eyes. Complications were similar to those seen after
      trabeculectomy. This method is efficient for severely glaucomatous eyes that are
      difficult to manage with trabeculectomy alone.

PMID- 15580977
TI  - Pseudoduplication of optic disc on optical coherence tomography.

PMID- 15580978
TI  - Classification criteria for systemic lupus erythematosus: a review.
AB  - The Systemic Lupus International Collaborating Clinics, in preparation for
      revising the ACR classification criteria for systemic lupus erythematosus,
      reviewed the current classification criteria. These critical reviews, discussed
      at the Lund, Sweden, meeting in 2003, will be useful to the clinician and to the
      researcher. This paper reviews and critiques previous classification attempts.

PMID- 15580979
TI  - Dermatology position paper on the revision of the 1982 ACR criteria for systemic
      lupus erythematosus.
AB  - The 1982 ACR classification criteria have become de facto diagnostic criteria for
      systemic lupus erythematosus (SLE), but a review of the criteria is necessary to
      include recent diagnostic tests. The criteria were not developed with the help of
      dermatologists, and assign too much weight to the skin as one expression of a
      multiorgan disease. Consequently, patients with skin diseases are classified as
      SLE based mostly on skin symptoms. We discuss specific problems with each
      dermatologic criterion, but changes must await a new study. We suggest the
      following guidelines for such a study, aimed at revision of the criteria. 1) The
      SLE patient group should be recruited in part by dermatologists. 2) The study
      should evaluate an appropriate international ethnic/racial mix, including late
      onset SLE as well as pediatric patients. 3) All patients should have current
      laboratory and clinical evaluations, as suggested in the paper, to assure the
      criteria can be up-to-date. This includes anti-SS-A and anti-SS-B antibodies and
      skin biopsies for suspected cutaneous lupus erythematosus except for nonscarring
      alopecia and oral ulcers. 4) The study should be based on a series of transparent
      power calculations. 5) The control groups should represent relevant differential
      diagnoses in numbers large enough to assess diagnostic problems that might be
      specific to these differential diagnoses. In order to demonstrate specificity of
      the criteria with a 95% confidence interval between 90 and 100%, each control
      group of the above should have at least 73 patients.

PMID- 15580980
TI  - Musculoskeletal involvement in systemic lupus erythematosus.
AB  - Involvement of the musculoskeletal system is common if not universal in the
      clinical course of systemic lupus erythematosus (SLE). Joint involvement on the
      whole does not cause major erosive disease, however, recent developments in
      musculoskeletal imaging show clearly the presence of significant bony and soft
      tissue involvement. It might well explain the frequently observed discordance
      between the clinical signs and the articular symptoms assuming that fibromyalgia
      has been excluded. The clear demonstration of tendon involvement in SLE by MRI
      would merit considering tendonitis and tenosynovitis as candidates for inclusion
      in the diagnostic criteria.

PMID- 15580981
TI  - Proposed modifications to 1982 ACR classification criteria for systemic lupus
      erythematosus: serositis criterion.
AB  - The SLICC group believed that the definition of pleuritis should be expanded to
      include new pleural thickening and pericarditis to include characteristic
      history. Furthermore, SLICC suggested the addition of abdominal serositis to the
      current serositis criterion, manifested as either diffuse abdominal pain, with
      rebound or guarding, and/or ascites or bowel wall edema in the absence of other
      causes. Abdominal serositis can be secondary to either acute or chronic lupus
      peritonitis, with the former usually presenting as acute, generalized pain, and
      the latter as painless ascites.

PMID- 15580982
TI  - Review of ACR renal criteria in systemic lupus erythematosus.
AB  - The American College of Rheumatology renal criteria require re-evaluation to
      incorporate recent advances in the classification of glomerulonephritidies. Renal
      biopsy is now common and safely performed by experienced nephrologists in
      community as well as academic settings. The optimal criterion is renal
      histopathology findings of an immune complex mediated glomerulonephritis as
      interpreted by an experienced pathologist employing accepted criteria. Renal
      biopsies should be analysed by routine histopathology, immunofluorescent and
      electron microscopy. Rating of activity and chronicity should be noted. Secondary
      criteria for patients unable to undergo renal biopsy includes a combination of
      findings. These include proteinuria, hypocomplementemia, elevated anti-dsDNA
      antibodies and an active urine sediment. Proteinuria is a nonspecific finding
      and, most importantly, can be associated with a number of comorbidities including
      diabetes, hypertension and atherosclerotic disease. Persistent proteinuria > 0.5
      g per day or a spot protein to creatine ratio of > 0.5 should be accompanied by
      an additional feature supporting active lupus such as positive serologies
      (hypocomplementemia and/or elevated anti-dsDNA antibodies) and/or active urinary
      sediment. Similarly, active urinary sediment should be accompanied by the
      additional criterion of proteinuria to meet renal criteria. Decline in renal
      function is not a reliable criterion given the numerous medications,
      comorbidities and other clinical circumstances which may result in this feature.

PMID- 15580983
TI  - ACR classification criteria for systemic lupus erythematosus: limitations and
      revisions to neuropsychiatric variables.
AB  - There are a wide variety of neurologic (N) and psychiatric (P) manifestations of
      systemic lupus erythematosus (SLE) which extend beyond those identified in the
      current American College of Rheumatology (ACR) classification criteria for SLE.
      Several attempts have been made to devise a classification of NP-SLE
      manifestations. The most recent is the ACR nomenclature and case definitions for
      19 NP lupus syndromes which currently provides the best means of a standardized
      approach to categorize NP events in SLE patients. Data from a number of studies
      has indicated a wide variability in the prevalence of the 19 NP syndromes. On the
      basis of these findings and utilizing the guidelines provided in the case
      definitions for diagnosis and exclusion of confounding variables, it is proposed
      to examine a number of NP manifestations for possible inclusion in revised
      classification and diagnostic criteria for SLE.

PMID- 15580984
TI  - Review of ACR hematologic criteria in systemic lupus erythematosus.
AB  - We have conducted a thorough literature review to evaluate the relative value of
      the hematologic criterion in making a diagnosis of systemic lupus erythematosus
      (SLE), its clinical relevance, and its prognostic significance. In the updated
      1982 ACR criteria, the presence of one or more of the four elements: 1) hemolytic
      anemia (with reticulocytosis); 2) leukopenia (<4000/microL on two or more
      occasions); 3) lymphopenia (< 1500/microL on two or more occasions); or 4)
      thrombocytopenia (< 100,000/microL in the absence of offending drugs) is now
      considered as a single hematologic disorder. The sensitivity and specificity of
      the individual elements of the hematologic criterion range from 18 to 46% and 89
      to 99%, respectively. The accuracy of the hematologic criterion requires proper
      interpretation. For example, many studies reported the presence of anemia that
      was not clearly defined and likely included anemia from etiologies other than
      hemolytic anemia, thereby causing an overestimation of the prevalence. In
      addition, medications such as corticosteroids and cytotoxic agents, and viral
      infections, can also contribute to a reduction in lymphocyte count. Despite these
      limitations, the SLICC committee recommends no change in the elements of the
      hematologic criterion when this criterion is properly interpreted and other
      causes of cytopenia are excluded.

PMID- 15580985
TI  - Antibodies and clinical features of the antiphospholipid syndrome as criteria for
      systemic lupus erythematosus.
AB  - The antiphospholipid syndrome (APS) can occur as a primary diagnosis or as a
      prominent feature of other diseases, predominantly systemic lupus erythematosus
      (SLE). The 1982 revised criteria for SLE were published prior to many of the
      studies which have illuminated current understanding of the antiphospholipid
      syndrome and several current clinical criteria for SLE, when arising from
      thrombotic damage to different organ systems, could be attributed to APS, leading
      to some confusion about where the diagnoses of these two disorders should begin
      and end. Additionally, APS is a significant generalized risk factor for
      irreversible organ damage and overall mortality in SLE patients and genetic
      linkages to HLA in APS hold up whether the disorder is primary or linked to SLE.
      It is increasingly recognized that APS itself is a complex, heterogenous
      disorder, involving a spectrum of autoantibodies to phospholipid-binding
      proteins, many of which have known coagulation-regulating functions. Although the
      combination of more than one antiphospholipid-related antibody might indicate a
      more severe phenotype, it is not suggested here that additive criteria for the
      diagnosis of SLE be accumulated with more than one of these pathologically
      related autoantibodies. Patients with multiple criteria for APS should be
      considered to have severe APS but it would be recommended to restrict APS
      attributed criteria for SLE to a maximal of two: one immunologic and one
      clinical. Thus people meeting the Sapporo criteria for APS could gain only a
      maximum of two criteria for SLE, regardless of how many autoantibodies were
      detected or how severe the clinical syndrome might be. This would allow
      manifestations of fullblown APS an appropriate impact towards the diagnosis of
      SLE without leading to a premature diagnosis of SLE for people who might better
      be considered to have moderate to severe primary APS.

PMID- 15580986
TI  - ACR classification criteria for systemic lupus erythematosus: complement
      components.
AB  - Complement is involved in the pathogenesis of systemic lupus erythematosus (SLE)
      and has also a seemingly paradoxical protective role in the development of the
      disease. Low levels of components within the classical pathway of complement
      especially C1q, C4 and C3 have a high specificity for SLE diagnosis and should be
      considered as promising for inclusion in classification criteria of SLE.

PMID- 15580987
TI  - Anti-dsDNA antibodies: still a useful criterion for patients with systemic lupus
      erythematosus?
AB  - The presence of antibodies to dsDNA has been a criterion for systemic lupus
      erythematosus (SLE) in each of three attempts to classify the disease that have
      been undertaken by the American College of Rheumatology. The generally good
      specificity of the test, the fact that it is widely available and often
      undertaken by an enzyme linked immunosorbent assay (ELISA) which is relatively
      cheap and easy to perform have encouraged its continued presence in the list of
      lupus criteria. The detection of anti-dsDNA antibodies is not, however,
      straightforward and the real significance of the presence of these antibodies,
      their true specificity (or otherwise), the question of whether they are truly
      linked to disease pathogenicity and how accurately they reflect disease activity
      are all questions that have been posed in the past 20 years.

PMID- 15580988
TI  - From sludge to resources through biosolids.
AB  - The paper gives an overview of the possibilities to achieve a more sustainable
      sludge management strategy by recovering and reusing valuable products as much as
      possible. Discussion separately deals with the recovery of products suitable for
      "material" uses and those for "energy" ones. Discussion on material recoveries
      includes organic matter, nutrients, carbon source, coagulant, bricks, pumice,
      slag, artificial lightweight aggregate (ALWA) and Portland cement. Regarding
      energy recovery, (i) conversion processes, including thermo-chemical conversion
      of dry sludge to oil, thermo-chemical liquefaction of wet sludge to oil and
      conversion/combustion processes, (ii) deep shaft wet air oxidation, and (iii)
      gasification processes, including starved air combustion, are outlined. Only
      general indications are given because the selection of an appropriate system for
      sludge management is strongly influenced by many other important factors, such as
      local economy and geography, climate, land use, regulatory constraints and public
      acceptance of the various practices. Also, the conventional and more traditional
      recycling options, like agricultural and other land uses, and incineration with
      energy recovery, are not dealt with because they are well known and extensively
      discussed elsewhere.

PMID- 15580989
TI  - Use of drainability and filterability simulations for evaluation of oxidative
      treatment and polymer conditioning of sludge.
AB  - In the traditional view of sludge structure, a two-phase system is visualized.
      The solid phase is often illustrated as consisting of uniform, spherical,
      negatively charged particles. This simplistic picture limits the understanding of
      both conditioning and dewatering. Specifically, it limits us to only two
      strategies for destabiiization: charge neutralization (using cationic coagulant
      species with either uniform or patch effects), and bridging (using polymeric
      flocculants). In fact, the situation is more complex in many respects. In this
      paper, we compared chemical conditioning of anaerobically digested biosolids
      using (1) conventional polymeric flocculation, and (2) treatment by chemical
      oxidants. Since these strategies may alter dewatering behavior by very different
      mechanisms, we report comparisons using a lab-scale simulator of belt press
      dewatering, including separate steps for the drainage and filtration processes.
      This allows greater insight into the effects of these conditioning methods and
      how they might be properly employed.

PMID- 15580990
TI  - Use of microwave pretreatment for enhanced anaerobiosis of secondary sludge.
AB  - This work elucidates the effects of pretreatment of secondary sludge by microwave
      irradiation on anaerobic digestion. The soluble chemical oxygen demand (COD)
      concentration increased up to 22% as microwave irradiation time increased, which
      indicated the sludge particles disintegrated. Three identical automated
      bioreactors with working volume of 5 l were used as anaerobic digesters at
      mesophilic temperature (35 degrees C). The reactors were separately fed with
      sludge with microwave pretreated- and control- sludge at different hydraulic
      retention times (HRT). The volatile solid (VS) reduction in the control operation
      was approximately 23.2 +/- 1.3%, while it was 25.7 +/- 0.8% for the reactors with
      the pretreated sludge. The average biogas production rate with the pretreated
      sludge at 8, 10, 12, and 15 days HRTs was 240 +/- 11, 183 +/- 9, 147 +/- 8, and
      117 +/- 7 ml/l/d respectively, while those with the control sludge were 134 +/-
      12 and 94 +/- 7 ml/l/d at 10 and 15 days HRTs. Maximum rates of COD removal and
      methane production with the pretreated sludge were 64% and 79% higher than those
      of the control system, respectively.

PMID- 15580991
TI  - Ultrasonic sludge treatment for enhanced anaerobic digestion.
AB  - Ultrasound is the term used to describe sound energy at frequencies above 20 kHz.
      High-powered ultrasound can be applied to a waste stream via purpose-designed
      tools in order to induce cavitation. This effect results in the rupture of
      cellular material and reduction of particle size in the waste stream, making the
      cells more amenable to downstream processing. sonix is a new technology utilising
      high-powered, concentrated ultrasound for conditioning sludges prior to further
      treatment. This paper presents recent results from a number of demonstration and
      full-scale plants treating thickened waste activated sludge (TWAS) prior to
      anaerobic digestion, therefore enhancing the process. The present studies have
      proved that the use of ultrasound to enhance anaerobic digestion can be achieved
      at full scale and effectively result in the TWAS (typically difficult to digest)
      behaving, after sonication, as if it were a "primary" sludge. The technology
      presents benefits in terms of increased biogas production, better solids
      reduction, improved dewatering characteristics of the digested sludge mixture and
      relatively short payback periods of two years or less subject to the site
      conditions and practices applicable at that time.

PMID- 15580992
TI  - Effect of the application of acid treated biosolids on marigold (Tagetes erecta)
      development.
AB  - The use of biosolids for land restoration and crop production is a potential
      solution to improve food production worldwide. However, the microbial content
      usually restricts its application in crops that are consumed uncooked. An
      alternative practice is their use in floriculture. In this study, the effects of
      acid treated sludge on the development of marigold (Tagetes erecta) plants were
      evaluated under green house conditions. Biosolids were applied at the agronomic
      rate (AR) based on nitrogen requirements of the marigold. In addition, higher
      rates (10 and 20xAR) were applied to study their effect on the plants. Biosolids
      were mixed with tepetate (hard volcanic indurate layers). Due to its origin,
      tepetate lacks nutrients and organic matter to adequately support plant
      development. The best treatment for marigold development was 10xAR, as plants
      reached an average height of 107 cm, with a growing speed of 1.01 cm/d, which is
      20 times more than the control. Plants that received no biosolids produced 0.25
      buds and 0.5 flowers per plant. In contrast, AR and 10xAR showed a production
      that ranged from 2 to 29 buds/plant and 4 to 15 flowers/plant, respectively.
      These results indicate the viability of reusing acid treated biosolids to improve
      marigold development.

PMID- 15580993
TI  - Co-conditioning and dewatering of alum sludge and waste activated sludge.
AB  - Co-conditioning and dewatering behaviors of alum sludge and waste activated
      sludge were investigated. Two different sludges were mixed at various ratios
      (2:1; 1:1; 1:2; 1:4) for study. Capillary suction time (CST) and specific
      resistance to filtration (SRF) were utilized to assess sludge dewaterability.
      Relatively speaking, waste activated sludge, though of higher solid content, was
      more difficult to be dewatered than alum sludge. It was found that sludge
      dewaterability and settlability became better with increasing fraction of alum
      sludge in the mixed sludge. Dosage required of the cationic polyelectrolyte (KP
      201C) for dewatering was reduced as well. It is proposed that alum sludge acts as
      skeleton builder in the mixed sludge, and renders the mixed sludge more
      incompressible which is beneficial for sludge dewatering. Implications of the
      results of the study to the sludge management plan for Taipei City that generates
      both alum sludge and waste activated sludge at significant amount are also
      discussed. The current sludge treatment and disposal plan in Metropolitan Taipei
      could be made more cost-effective.

PMID- 15580994
TI  - The role of carbohydrate and protein parts of extracellular polymeric substances
      on the dewaterability of biological sludges.
AB  - There are many factors affecting the biological sludge dewaterability such as
      particle size distribution, floc structure, extracellular polymeric substances
      (EPS), etc. In this research, the role of the protein and carbohydrate parts of
      EPS (EPS(carbohydrate), and EPS(protein)) on the dewaterability of biological
      sludges was investigated. The sludge EPS composition was altered by feeding the
      sludges of same origin, in different reactors, with synthetic media having carbon
      to nitrogen (C/N) ratios of 8, 19 and 30 (in terms of COD/NH3-N), respectively.
      EPS in sludge samples were extracted by a cation exchange resin (CER). The
      characteristics of EPS were investigated by analytical methods and by using FT-IR
      spectroscopy. The dewaterability of the sludges was determined in terms of
      filterability and compactibility. Filterability, as filterability constant (X),
      and compactibility, as cake solids concentration, of sludges were determined by
      using the capillary suction time (CST) test and the centrifugation, respectively.
      The floc structure of sludge samples was also observed microscopically.
      Filterability and compactibility of the sludge samples were improved considerably
      with the increasing carbohydrate part and the decreasing protein part of the
      sludge EPS. EPS(protein) was inversely related to the cake solids concentration,
      which might be explained by the water holding capacity of EPS(protein).
      Filterability and compactibility of sludges improved by the increase of the size
      and strength of the flocs.

PMID- 15580995
TI  - The effects of nano-materials on the behaviors of sludge mortar specimens.
AB  - In this research, nano-composites are added to sewage sludge ash to create a
      mixture, which then replaces part of cement. Nano-composites are manufactured
      from pure quartzose sand. The influences of different amounts of nano-composites
      and sludge ash on mortar are evaluated. Cement, sludge ash (0%, 10%, and 20%),
      and nano-composites (0%, 0.5%, 1%, 2%, and 3%), which defined as the percent
      weight of cement and sludge ash, are mixed together in batches to make mortar
      specimens. Results show that the flowability of sludge ash mortar reduces with
      increasing amount of cement replaced and of nano-composites added. The
      compressive strength of mortar lowers when more amounts of cement are replaced by
      sludge ash, but increases with more quantity of nano-composites added. Moreover,
      the study shows that nano-composites can fortify the compressive strength of
      mortar. With the help of efficiency of compressive strength, nano-composites
      benefit most to the mortar with replacement of 10% sludge ash, followed by the
      substitution of 20% and 0%.

PMID- 15580996
TI  - Disinfection kinetics of pathogens in physicochemical sludge treated with
      ammonia.
AB  - Ammonia is a disinfectant which can diffuse through the membrane of highly
      resistant structures like helminth ova. Thus, it can be considered an alternative
      disinfectant of wastewater sludge with high pathogenic content. In this study,
      the kinetic parameters of the Hom model were used to describe the inactivation
      with ammonia of faecal coliforms, Salmonella spp. and viable helminth ova. These
      were obtained in processes considering the addition of ammonia alone as well as
      for ammonia combined with an increase in temperature. The sludge was sampled from
      a municipal wastewater treatment plant using an APT (Advanced Primary Treatment)
      or CEP (Chemical Enhanced Primary) process. With 20% w/w of ammonia, 7 logs of
      faecal coliforms, 6 logs of Salmonella spp., and 83% of viable helminth ova were
      reduced in 2 hours contact time. To eliminate 100% of the helminth ova from
      samples having 88-132 ova/g TS it was needed to combine 20% of ammonia with 50
      degrees C. The analysis of parameters k, n and m indicate higher resistance to
      inactivation of helminth ova compared to bacteria and a better performance of the
      ammonia process than lime stabilization to inactivate microorganisms. In
      addition, ammonia increased the agricultural value of the biosolids produced.

PMID- 15580997
TI  - Dynamic of lead speciation in sewage sludge composting.
AB  - A large-scale sewage sludge composting experiment was conducted to develop an
      understanding of changes that occur to Pb chemical speciation, distribution and
      bio-availability during the course of composting. The four-stage Tessier
      sequential extraction method was employed to investigate the dynamics of heavy
      metal Pb speciation (exchangeable, bound to carbonates, bound to Fe-Mn oxides,
      bound to organic matter and sulphides, residual) during the course of sewage
      sludge composting. The concentrations of the total Pb and the five Pb fractions
      concentrations were increased during the whole stage of compost. However, the
      percentages of Pb distribution with respect to total Pb were changed in the
      following manner: exchangeable, bound to Fe-Mn oxides and bound to carbonates Pb
      with respect to total Pb were increased, while the percentages of bound to
      organic matter and sulphides, and residual Pb with respect to total Pb were
      decreased during composting. The data showed that the quantity of Pb in the less
      toxic portion, such as consisting of organic matter and sulphides bound and
      residual Pb, was increased, and that the contamination and bio-availability of
      heavy metal Pb in sewage sludge was reduced during the composting process.

PMID- 15580998
TI  - Enhanced heavy metal bioleaching efficiencies from anaerobically digested sewage
      sludge with coinoculation of Acidithiobacillus ferrooxidans ANYL-1 and
      Blastoschizomyces capitatus Y5.
AB  - Prolonged bioleaching period was required to remove heavy metals from
      anaerobically digested sewage sludge in the presence of low molecular weight
      organic acids. The purpose of the present study was therefore to enhance metal
      solubilization efficiencies through introducing organic acid-degrading
      microorganisms into this artificial bioleaching system. An acetic and propionic
      acid-degrading yeast Blastoschizomyces capitatus Y5 was successfully isolated
      from a local Yuen Long sewage sludge and it could achieve optimum growth in
      synthetic liquid media containing 2000 mg l(-1) acetic acid or 1000 mg l(-1)
      propionic acid. When it was inoculated simultaneously with Acidithiobacillus
      ferrooxidans ANYL-1 into anaerobically digested sewage sludge, which contained
      648 mg l(-1) acetic acid and 731 mg l(-1) propionic acid, both acids were
      completely decomposed within 24 hours. As a result, ferrous iron oxidation was
      greatly improved, resulting in enhanced metal solubilization. Compared with the
      8, 10 and 12 days required for maximum solubilization of Zn, Cu and Cr for the
      control sludge, the bioleaching period was significantly shortened to 4, 5 and 8
      days respectively for sludge receiving co-inoculation.

PMID- 15580999
TI  - A comparison of ultrasound treatment on primary and secondary sludges.
AB  - Ultrasound treatment of primary and secondary sludges was conducted to improve
      the qualities of sludges for the anaerobic digestion. The impacts of different
      sonication times, sonication densities and solids concentrations on
      ultrasonication efficiency were examined. The experimental results indicated that
      the significant reduction in particle size and increase in soluble organics could
      be achieved, implying that ultrasonication could offer a feasible treatment
      method to efficiently disintegrate sludge. The greater decrease in particle size
      and increase in soluble organics of sludge indicated that the secondary sludge
      has a more remarkable improvement after sonication over the primary sludge. With
      respects to the extent of disintegration and energy consumption, higher
      sonication density performed more effectively in terms of specific energy. There
      exists an optimal solids concentration range for both the sludges for optimum
      sonication. Within the optimal solids concentration range, efficient sonication
      can be effected and sludge would be disintegrated efficiently. The ultrasound
      would be attenuated by scattering and absorption if the solids concentration
      exceeds the optimal range. It appeared from the study that the mechanical shear
      forces caused by ultrasonic cavitation could be a key factor for sludge
      disintegration and collapse of cavitation bubbles could significantly alter the
      sludge characteristics.

PMID- 15581000
TI  - Acidic and hydrogen peroxide treatment of polyaluminum chloride (PACL) sludge
      from water treatment.
AB  - The water treatment sludge including coagulants cannot be easily removed by
      conventional dewatering methods. The possibility of hydrogen peroxide (H2O2)
      oxidation as a pretreatment to enhance the dewaterability of polyaluminum
      chloride (PACl) sludge from water works was investigated. H2O2 treatment alone
      was not effective but H2O2 treatment under acidic condition significantly reduced
      both the cake water content and specific resistance to filtration (SRF),
      indicating the enhancement of dewaterability and filterability. The filterability
      after acid/H2O2 treatment was comparable to polymer conditioning and even more
      dewatered cake than polymer conditioning was produced. By H202 combined with
      sulfuric acid (H2SO4), leached iron caused Fenton's reaction, which showed a
      potential to significantly reduce the amount of solids mass and to produce more
      compact cake with higher filterability.

PMID- 15581001
TI  - Anaerobic co-digestion of sewage sludge and food waste using temperature-phased
      anaerobic digestion process.
AB  - This study was performed to overcome the low efficiency of anaerobic digestion of
      sewage sludge and food waste by combining temperature-phased digestion,
      sequencing batch operation, and co-digestion technology. It was demonstrated that
      the temperature-phased anaerobic sequencing batch reactor (TPASBR) system for the
      co-digestion of sewage sludge and food waste resulted in enhanced volatile solids
      (VS) reduction and methane production rate. At the organic loading rate (OLR) of
      2.7 g VS/l/d, the TPASBR system showed the higher VS reduction (61.3%), CH4 yield
      (0.28 l/g VS(added)) and CH4 production rate (0.41 l CH4/l/d) than those (0.29 l
      CH4/l/d) of the mesophilic two-stage ASBR (MTSASBR). In the specific methanogenic
      activity (SMA) tests on thermophilic biomass of the TPASBR system, the average
      SMA of acetate (93 ml CH4/gVSS/d) was much higher than those of propionate (46 ml
      CH4/g VSS/d) and butyrate (76 ml CH4/g VSS/d). Also, higher specific hydrolytic
      activity (SHA, 217 mg COD/g VSS/d) of the biomass supported fast hydrolysis under
      thermophilic conditions. The track study revealed that the most active period of
      the 24 h cycle was between 6 and 12 h. The enhanced performance of the TPASBR
      system could be attributed to longer solids retention time, fast hydrolysis,
      higher CH4 conversion rate, and balanced nutrient condition of co-substrate. It
      was verified that this combination could be a promising and practical alternative
      for the simultaneous recycling of two types of organic fraction of municipal
      solid waste (OFMSW) with high stability.

PMID- 15581002
TI  - Reactivation and/or growth of fecal coliform bacteria during centrifugal
      dewatering of anaerobically digested biosolids.
AB  - Fecal coliform bacteria are used as indicator organisms for the presence of
      pathogens. In sludges, it has often been assumed that the counts of fecal
      coliforms after digestion (where the sludges may also be called biosolids) are
      representative of the counts when the sludge is disposed or recycled, such as by
      land application. The possibility has been raised, however, that dewatering
      processes can lead to increased counts of fecal coliforms and, by inference,
      human pathogens. This paper presents data from previous studies of this
      possibility; the results were inconsistent but showed observable increases in
      fecal coliforms at one treatment plant. Additional studies were then performed at
      another treatment facility, which showed statistically significant increases in
      fecal coliform counts after dewatering and two days of aging. The increases
      exceeded two orders of magnitude and included two centrifuge types and two
      biosolids types. Artifacts of media type and enumeration method have been
      excluded, and shearing of the material by commercial blender did not produce the
      same effects.

PMID- 15581003
TI  - Minimization of sludge production and stable operational condition of a submerged
      membrane activated sludge process.
AB  - Modification of conventional activated sludge process by adding microfiltration
      type hollow fiber membrane module offers various advantages. The membrane module
      is immersed directly in the bioreactor to separate the treated water from the
      sludge and the modified process is called submerged membrane activated sludge
      process (SMASP). Bench scale SMASP units were operated at constant flux to study
      the possibility of minimizing the excess sludge production and stable operation
      at different SRT and BOD loading. The long SRT developed high stabilized MLSS
      concentration in the bioreactor and decreased the sludge loading rate [kg-BOD/kg
      MLSS-d]. In SMASP, very low sludge yield coefficients (0.04-0.09 kg-MLSS/kg-BOD)
      were obtained at long SRT (500 d) and small BOD loading (< or =0.5 kg/(m3 x d))
      as compared to conventional activated sludge process and these coefficients
      showed considerable minimization in excess activated sludge production. At the
      same operation conditions, suction pressure was also maintained low (<25 kPa),
      and then SMASP was operated stably for long time (approximately 200 d).

PMID- 15581004
TI  - Physical characteristics of a waste activated sludge: conditioning responses and
      correlations with a synthetic surrogate.
AB  - The efficient and economic management of waste activated sludge (WAS) requires a
      proper understanding of the sludge's material properties. Though there has been
      much study of WAS, an adequate linkage between its physical and chemical
      properties has been elusive. In particular, the conditioning and dewatering of
      WAS are expensive operations, and the addition of polymer to WAS leads to even
      more complex material behavior that is difficult to optimize. This paper reports
      on an extensive characterization of WAS, both with and without polymer
      conditioning. We combined the classical "jar test" approach with less
      conventional rheometric and electrokinetic measurements. In addition to the use
      of sampled WAS, a synthetic surrogate sludge was formulated, attempting to
      duplicate properties of WAS and allow more extensive characterization of a
      reproducible surrogate to WAS. Results with both the synthetic surrogate and WAS
      indicated that the traditional, electrokinetic, and rheological properties were
      related. However, the dose optima by rheometry were somewhat higher in both
      cases.

PMID- 15581005
TI  - Development of extraction procedures for the analysis of polycyclic aromatic
      hydrocarbons and organochlorine pesticides in municipal sewage sludge.
AB  - Land application of sludge as fertilizers is a way of disposal and recycling of
      sludge. However, public concern has arisen due to the fact that organic
      contaminants in sludge may ultimately enter the food chain. Hence the need arises
      to analyse the organic contaminants such as PAHs and OCPs in sludge. In this
      study, Soxhlet was utilised as the extraction method and the extracts subjected
      to extensive cleanup via either silica columns or solid phase extraction
      cartridges prior to analysis using gas chromatography or high performance liquid
      chromatography. Sludge samples were collected from the drying beds of oxidation
      ponds in three locations in South Johore. OCPs such as heptachlor, dieldrin and
      pp-DDT were detected in low amounts (52-159 mg/kg) whereas PAHs such as
      naphthalene, phenanthrene, fluoranthene and benzo(a)pyrene were detected in the
      range of 0.2-5.5 mg/kg dry mass. Subcritical water extraction (SWE) recovery
      studies of PAHs were also performed from spiked sludge samples. Although a
      recovery range of 41-68% was obtained using the SWE method, the results indicated
      the usefulness of the technique as an alternative to Soxhlet extraction for the
      analysis of PAHs in sludge samples.

PMID- 15581006
TI  - An innovative sludge management system based on separation of primary and
      secondary sludge treatment.
AB  - An innovative sludge management system based on separation of treatment and
      disposal of primary and secondary sludge is discussed with reference to a sewage
      treatment plant of 500,000 equivalent person capacity. Secondary sludge, if
      treated separately from primary sludge, can be recovered in agriculture
      considering its relatively high content of nitrogen and phosphorus and negligible
      presence of pathogens and micropollutants. One typical outlet for primary sludge
      is still incineration which can be optimised by rendering the process auto
      thermal and significantly reducing the size of the incineration plant units
      (dryer, fluidised bed furnace, boiler and units for exhaust gas treatment) in
      comparison with those required for mixed sludge incineration. Biogas produced in
      anaerobic digestion is totally available for energy conversion when sludge
      treatment separation is performed, while in the other case a large proportion may
      be used as fuel in incineration, thus reducing the net electric energy conversion
      from 0.85-0.9 to 0.35-0.4 MW for the plant considered.

PMID- 15581007
TI  - Removal of dissolved copper(II) and zinc(II) by aerobic granular sludge.
AB  - This study investigated the adsorption kinetics of dissolved copper(II) and
      zinc(II) by aerobic granular sludge. Two series of batch experiments were
      conducted at different initial copper(II), zinc(II) concentrations (Co) and
      initial granule concentrations (Xo). Results showed that the biosorption kinetics
      of individual copper(II) and zinc(II) by aerobic granules were closely related to
      Co and Xo. The maximum biosorption capacity of individual copper(II) and zinc(II)
      by aerobic granules was 246.1 mg g(-1) and 180 mg g(-1), respectively. In order
      to theoretically interpret the results obtained, two kinetic models previously
      developed for biosorption were employed and compared in this study. It was found
      that the model proposed by Liu et al. (2003) could fit the experimental data very
      well, but the second-order model failed to fit the data in some cases. It appears
      that aerobic granules would be potential biosorbent with high efficiency for the
      removal of dissolved copper(II) and zinc(II) from wastewater.

PMID- 15581008
TI  - Direct generation of electricity from sludges and other liquid wastes.
AB  - Recently it has been shown that electrical energy can be harvested from marine
      sediments, simply by connection of an electrode (anode) in anaerobic marine
      sediments to an electrode in the aerobic zone above the sediments. We have now
      shown that similar applications are available in sludge treatment. Using a
      reactor with graphite foil electrodes in an aerated aerobic and anaerobic sludge
      zone, electrical current was generated, and enhanced when an additional organic
      substrate (acetate) was added. Electron microscopy, x-ray diffraction, and PCR
      examination of the anode surface showed no surface colonization and no increase
      in Geobacter relative to a control, indicating that microbial use of the anode as
      an electron acceptor wa indirect through the use of redox mediators. Given the
      demonstration of electricity generation from sludge, the potential for similar
      applications, using other organic waste sources, is evaluated.

PMID- 15581009
TI  - Energy and nutrient recovery from sewage sludge via pyrolysis.
AB  - Energy recovery and nutrient reuse from sewage sludge has traditionally been
      achieved via anaerobic digestion/power generation with land application of the
      biosolids. By contrast, thermal processes such as pyrolysis have typically been
      used only for energy recovery. One such technology has demonstrated at commercial
      scale that all of the energy in sludge can be beneficially recovered and reused.
      No attempt was however made to recover and reuse sludge nutrients. There are many
      potential benefits of using pyrolysis for both energy and nutrient recovery.
      Firstly, unlike digestion, the principal energy product is oil, which can readily
      be stored and used when required, ensuring that energy recovery is maximised.
      Secondly is that the sludge nutrients are recovered in the pyrolysis char.
      Laboratory soil incubation studies using char from the Subiaco demonstration
      plant were conducted over an eight-week period to confirm nutrient availability.
      Results from this study showed that the phosphorus in the char is plant available
      although the nitrogen was insoluble. Based on these results it appears that there
      is potential to use pyrolysis as an effective means to recover and reuse both the
      energy and the very valuable phosphorus present in sewage sludges.

PMID- 15581010
TI  - Thermal drying of wastewater sludge with crack formation.
AB  - We examined in this work the drying characteristics of wastewater sludge. The
      drying flux of the constant-rate period for sludge cake could be up to 40% higher
      than that from a sand bed. Owing to the considerable volume shrinkage of cake,
      cracks would form and develop on the crack surface, which yielded three
      dimensional but rather than the one-dimensional cake structure assumed in
      conventional drying theories. The crack length was fully developed in the first
      30 min of drying, while the width of crack increased linearly with time. Using
      these data the drying flux from the cracks was estimated. Enhanced drying flux
      was noticeable which depended on the crack shape and the crossflow velocity.

PMID- 15581011
TI  - Reuse of fresh water sludge in cement making.
AB  - With the increasing demand for high quality water, a large quantity of chemical
      agent must be added in the water purification process, which in turn generates
      enormous amount of fresh water sludge. Of all the options for sludge disposal,
      sludge reuse has been considered most economical and environmentally sound. This
      study evaluated the possibility of incorporating fresh water sludge in the making
      of Portland cement through the sintering process. The goal was to search for the
      optimal condition to maximize the replacement of clay with the fresh water
      sludge. Characteristics of fresh water sludge were collected and analyzed. The
      analysis showed that water source and water treatment process dominate th
      characteristics, particularly the chemical composition of the fresh water sludge.
      The fresh water sludge was mixed with the cement clay in various percentages,
      from 0% to 100%, as raw material for cement-making. The effects of its addition
      on the sintering condition and the quality of cement were evaluated. The analysis
      of the clinkers showed that the addition of the fresh water sludge did not change
      the phase form and the f-CaO content of the cement. The compressive strength of
      the masonry increased with the increasing addition of fresh water sludge. All
      cement products made from various replacement ratios met the Chinese National
      Standard of first degree Portland cement.

PMID- 15581012
TI  - Reuse of wastewater sludge with marine clay as a new resource of construction
      aggregates.
AB  - The disposal of sludge from wastewater treatment presents highly complex problems
      to any municipality. Most of the sludge disposal methods have varying degrees of
      environmental impact. Hence, it is necessary to explore potential areas of reuse
      in order to alleviate sludge disposal problems and to conserve natural resources.
      Industrial sludge and marine clay are two forms of high-volume wastes. Using
      these wastes as a resource of raw materials to produce construction aggregates
      would enable large-scale sludge reuse. The aggregates were produced at various
      sludge-clay combinations containing 0, 20, 50, 80 and 100% clay contents,
      respectively. The pelletized aggregates displayed lower particle densities ranged
      between 1.48 and 2.25 g/cm3, compared to the density of granite at 2.56 g/cm3.
      Good 28-day concrete compressive strength of 38.5 N/mm2 achieved by the 100%
      sludge aggregate was comparable to the value of 38.0 N/mm2 achieved of the
      granite control specimens. The leachate contamination levels from the aggregates
      after 150 days were found acceptable when used in concrete, indicating
      insignificant environmental contamination. The heat flow study showed increases
      in heat flow at the temperatures of 480 degrees C and between 660 degrees C and
      900 degrees C, indicating a need for the extension of heating time around these
      temperatures.

PMID- 15581013
TI  - Sludge as source of energy and revenue.
AB  - Sludge is a residue/product from wastewater treatment plants and contains most of
      the contaminants released during human activities. Some stringent environmental
      regulations on sludge treatment and disposal exist in many countries. This has
      resulted in increasing interest in sludge treatment methods that encourage sludge
      reduction and improvement in biogas production during anaerobic digestion
      processes. This work demonstrates the first exploitation of valuable energy from
      homogenised sludge at technical scale with mass reduction. The optimal
      combination of sludge homogenisation at relatively low pressures using a modified
      high-pressure homogeniser led to the success of this unique project. Results
      showed that about 30% more energy could be obtained from thickened and disrupted
      sludge than from untreated samples. The energy produced was higher than that
      invested during disruption and digestion processes. About 23% sludge reduction
      was also observed with no increase in chemical oxygen demand. This new process
      can produce extra energy for local electrification and heating the digester while
      the sludge reduction provides economic benefits. Concentration of sludge causes
      reduction in investment cost on digester as well as reduction in operational time
      for sludge dewatering.

PMID- 15581014
TI  - Processing dewatered sewage sludge using electrokinetic technology.
AB  - High content of heavy metals and presence of pathogens in the dewatered sewage
      sludge have been the main obstacles for land application of sewage sludge-made
      fertilizer. The aim of this study was to examine the effects of the innovative
      electrokinetic (EK) technology on removal of heavy metals from sewage sludge, on
      the reduction of pathogens, and on sludge chemical characteristics. The results
      showed that the removal efficiencies for Zn, Cu, Ni, Cr, As and Pb were 94.9%,
      95.4%, 89.7%, 67.8%, 31.2% and 18.7%, respectively. Acidification pretreatment of
      the dewatered sludge for 29 h decreased the content of heterotrophic bacteria
      from 1.5 x 10(8) c.f.u./g of wet sludge to 1.1 x 10(4) c.f.u./g of wet sludge.
      Although the initial content of total coliforms and fecal coliforms in sewage
      sludge were 5.8 x 10(5) c.f.u./g of wet sludge and 4.0 x 10(5) c.f.u./g of wet
      sludge, respectively, no viable cells were detected. Minor losses of K and N were
      detected, but the loss of P was found to be significant in EK treated sewage
      sludge. The treated sludge was technically considered as very stable based on the
      carbon dioxide evolution rate.

PMID- 15581015
TI  - Recovery of energy from sludge--comparison of the various options.
AB  - This paper gives a general discussion of existing sludge treatment processes and
      of innovative treatment options, especially focused on the valuable use of
      organic carbon compounds as an energy source. Attention is paid both to high and
      to low temperature processes and to combinations of these processes. Based on an
      assessment and comparison the most beneficial and sustainable options are
      identified and a rough indication is given of the possibilities for improvement
      and future developments.

PMID- 15581016
TI  - Production of hydrogen and methane from wastewater sludge using anaerobic
      fermentation.
AB  - The hydrogen and methane were produced from wastewater sludge using a Clostridium
      strain. The original sludge and the pre-treated (acidified, sterilized,
      freeze/thawed, and sonicated) sludges were tested. Some pre-treatment could
      enhance hydrogen yield, and the other tests could enhance methane yield. Hydrogen
      yield followed freeze/thawed>acidified>sterilized>original sludge>sonicated;
      while methane yield followed
      sonicated>freeze/thawed>sterilized>acidified>original sludge. The production and
      consumption of acetate correlated closely with the trends in both yields.

PMID- 15581017
TI  - Development of sludge based stable aqueous Bacillus thuringiensis formulations.
AB  - This study focuses on development of aqueous flowable (suspension) formulations
      for Bacillus thuringiensis (Bt) based biopesticides from wastewater sludge.
      Different inerts like sorbitol, sodium monophosphate, sodium metabisulphite,
      sorbic acid, propionic acid, Tween-80, Triton X-100 and glycerol were tested for
      formulations. Five different formulations for non-hydrolyzed (NH) secondary
      sludges were tried and the best combination selected on the basis of various
      physical parameters like viscosity, particle size, suspendibility,
      entomotoxicity, and microbiological purity tests. F5 formulations (for secondary
      sludge) comprising sorbitol, sodium monophosphate and sodium metabisulphite gave
      better physical and biological characteristics with a small effect on
      entomotoxicity and spore concentration after 120 days at pH 6, 6.5 and
      temperatures 40 and 50 degrees C and viscosity change at 40 and 50 degrees C. The
      formulations were more stable at pH 4.0 to 5.0 and temperatures 4 to 30 degrees C
      whereas at pH 6.0 and 6.5 and temperatures 40 and 50 degrees C, there was
      degeneration of the product. Lower proteolytic activity and physical factors like
      ionic strength and surface group changes at pH 6 and 6.5 were responsible for the
      instability of the formulation.

PMID- 15581018
TI  - Removal of polycyclic aromatic hydrocarbons (PAHs) from sewage sludge by
      anaerobic degradation.
AB  - Due to the hydrophobic nature of the polyaromatic hydrocarbons (PAHs) they are
      mostly bound to the sludge and escape aerobic treatment in a wastewater treatment
      plant. They therefore proceed directly to the anaerobic post treatment, terminate
      in the sludge, and can be released to the environment if land spreading is used.
      PAH degradation in anaerobic methanogenic systems has only recently been shown to
      occur. In this study we have assessed several factors of anaerobic PAH
      degradation by evaluating thermodynamic feasibility of degradation, assessing
      degradation at different temperatures, and investigating the enriched cultures
      using fluorescent in-situ hybridization (FISH). Thermodynamic calculations
      indicated that PAH degradation was possible under methanogenic conditions, in the
      presence of hydrogen utilizing methanogens. Removal of naphthalene and 1-methyl
      naphthalene depended both on temperature and the initial inoculum. Inocula
      sourced from contaminated land sites were the most effective. The enrichments
      were all a mixture of Bacteria, and Archaea, and the Archaea were generally
      identified as Methanobacteriales, using an order-specific probe. The bacteria
      were not specifically identified. The results indicate a syntrophic culture, with
      the bacteria oxidizing the naphthalene, and the Archaea converting the hydrogen
      produced by oxidation, to methane.

PMID- 15581019
TI  - Municipal sludge management and disposal in South Korea: status and a new
      sustainable approach.
AB  - Based on figures from 2002, 5216 ton/d of the municipal sludge is produced from
      184 large municipal wastewater treatment plants in 111 cities with total
      treatment capacity of 19,229,745 m3/d. Even though the large amount of sludge
      disposal has depended greatly on ocean disposal and landfills until recently, the
      fraction of sludge reuse has gradually increased from 2.7% to 7%, since 1991. Due
      to a need of resources recovery from the sludge, high cost requirement of
      incineration and legislative regulation, recent new research is mainly focused on
      resources recovery and its reuse from the municipal sludge, such as high
      performance acid fermenter with pathogen reduction, crystallization (struvite and
      hydroxyapatite) using waste lime, cofermentation of municipal sludge with food
      waste, aerobic composting with P crystallization, vermistabilization, lime
      treatment, etc. Current research and practical activities with some efforts for
      the new technical development as well as environmental law and regulation are
      reviewed.

PMID- 15581020
TI  - Births to 10-14 year-old mothers, 1990-2002: trends and health outcomes.
AB  - OBJECTIVES: This report presents the number and rate of U.S. births for 10-14
      year olds, for 1990-2002 by race and Hispanic origin and by State. Pregnancy risk
      factors and outcomes by selected maternal and infant characteristics are shown.
      METHODS: Tabular and graphical descriptions of births and infant deaths to 10-14
      year olds are presented based on information reported on birth and death
      certificates for the United States and each State. RESULTS: 7,315 females aged 10
      14 years delivered a live birth in 2002. The rate of births to 10-14 year olds
      was 0.7 per 1,000 in 2002, half of the rate during 1989-94. This rate peaked in
      1989 (1.4 per 1,000). For 1990-94 the rate remained at 1.4, and then began a
      steady decline to 0.7 per 1,000 in 2002. Large declines in young teenage
      childbearing were seen among all racial and ethnic subgroups, as well as almost
      all States. These young mothers were least likely to receive timely prenatal care
      compared with mothers of older age groups. Compared with infants of mothers aged
      20-39 years, infants of the youngest mothers experienced almost twice the rates
      of preterm delivery (21.3 percent) and low birthweight (12.6 percent). The infant
      mortality rate (15.4 per 1,000) was two to three times higher than that for
      infants of mothers aged 20-44 years.

PMID- 15581021
TI  - The neuropathology of melioidosis: two cases and a review of the literature.
AB  - Melioidosis is an infectious disease caused by Burkholderia pseudomallei and is
      hyperendemic in the Top End of the Northern Territory of Australia, as well as
      being widespread throughout tropical south east Asia. The infection is primarily
      acquired via the inoculation of compromised surface tissues by contaminated soils
      and water and it can cause an acute, rapidly fatal illness. Although pneumonia is
      the commonest manifestation, neurological presentations have been described, most
      notably encephalomyelitis. This paper presents the neuropathology of 2 fatal
      cases of neurological melioidosis and reviews the relevant literature.

PMID- 15581022
TI  - Isolated intracranial Rosai-Dorfman disease mimicking meningioma.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai
      Dorfman disease (RDD), is an idiopathic histiocytic proliferation affecting lymph
      nodes. It is typically characterized by painless cervical lymphadenopathy, fever
      and weight loss. Although extranodal involvement has been reported in diverse
      sites, intracranial presentation, particularly in the absence of nodal disease is
      uncommon. To the best of our knowledge, 48 patients with intracranial masses have
      been reported previously. A 31-year-old man was admitted to our clinic with a 4
      month history of progressive headache. His medical history was unremarkable
      except for occasional fever. There were not any neurological deficit and weight
      loss. No lymphadenopathy (particularly bilateral cervical) and extranodal
      involvement in diverse sites were revealed by physical and radiological
      examinations. Routine hematological and biochemical studies were normal except
      for mild leukocytosis and elevated erythrocyte sedimentation rate. The patient
      underwent magnetic resonance imaging (MRI) testing that revealed an enhancing
      mass in the left temporal lobe. Preoperative diagnosis was meningioma. The
      patient underwent a left frontotemporal craniotomy with complete resection of the
      mass. Histopathology was compatible with RDD. Extranodal RDD is rarely found
      intracranially. Prognosis is benign especially in the absence of nodal disease.
      It is clinically and radiologically difficult to distinguish from meningioma, and
      histological examination is essential for a definitive diagnosis.

PMID- 15581023
TI  - Molecular abnormalities in pediatric embryonal brain tumors--analysis of loss of
      heterozygosity on chromosomes 1, 5, 9, 10, 11, 16, 17 and 22.
AB  - Embryonal tumors, the most common group of malignant brain tumors in childhood,
      are heterogeneous and have been associated with a large number of genetic
      abnormalities. The aim of this study was to comprehensively analyze loss of
      heterozygosity (LOH) on regions harboring suppressor genes (PTCH2, PTCH1, APC,
      PTEN, DMBT1, SUFU, AXIN1, hSNF5/INI1) and to study chromosomal regions in which
      deletions have been described most frequently (1p, 1q, 11p, 16p, 17p). Twenty
      nine children (17 male and 12 female), aged from 1 year 13 years were included in
      this study. There were 24 medulloblastomas (MB) and 5 supratentorial primitive
      neuroectodermal tumors (sPNET). Tissue samples from 29 primary and 11 recurrent
      tumors were analyzed according to the LOH standard procedures, which were
      extended to include fluorescence in situ hybridization for detection of
      isochromosome 17q (i(17q)) and direct sequencing ofTP53 exon 4. LOH on 17p was
      found in 15 out of 29 tumors. FISH analysis identified the presence of i(17q) in
      16 tumors. Comparison of LOH analysis and the FISH data indicated that
      alterations of 17p were related to be the introduction of an i(17q) formation.
      LOH on 10q and 9q was observed in 4 and 2 cases, respectively, and was associated
      with alterations of chromosome 17. These results indicated a connection between
      alterations of PTCH/SHH genes and abnormalities of chromosome 17. A deleted
      region on 22q, covering the hSNF5/INI1 locus, was observed in 3 tumors.
      Progression of the molecular changes occurred in 1 case of recurrent
      medulloblastoma. LOH on 10q and 17p was found in both primary and recurrent
      tumor, while losses on 11p, 16p, and 16q occurred only in the recurrent tumor. No
      evidence of alteration in TP53 exon 4 was identified.

PMID- 15581024
TI  - Mixed cystic gliosarcoma and primitive neuroectodermal tumor: a case report.
AB  - The clinical and pathologic features of a mixed (composite) gliosarcoma and
      primitive neuroectodermal tumor occurring in a 54-year-old male are presented. A
      large cyst and the presence of Rosenthal fibers are also unusual features of this
      tumor. To our knowledge, such a morphologically variegated tumor has not
      previously been reported.

PMID- 15581025
TI  - Expression of multidrug transporters in dysembryoplastic neuroepithelial tumors
      causing intractable epilepsy.
AB  - OBJECTIVE: Dysembryoplastic neuroepithelial tumors (DNT) are relatively benign
      brain lesions that often cause medically intractable epilepsy. There is mounting
      evidence that multidrug transporters such as P-glycoprotein (P-gp) or multidrug
      resistance-associated proteins (MRP) play an important role in the development of
      resistance to antiepileptic drugs (AED). MATERIAL AND METHODS: In the present
      study, we examined the expression of several multidrug transporters in 14 cases
      of DNT. The peritumoral brain tissue as well as 9 cases of arteriovenous
      malformations (AVM) served as controls. P-gp, MRP2, MRP5 and breast cancer
      resistance protein (BCRP) expression was evaluated qualitatively and
      quantitatively using immunohistochemistry. RESULTS: All transporters were
      overexpressed quantitatively in DNT, but each revealed a different labeling
      pattern. P-gp and BCRP were predominantly located in the endothelium of brain
      vessels. MRP5 was detected primarily in endothelial cells, but notably also in
      neurons. The expression of P-gp, MRP2 and MRP5 was low in AVM, whereas BCRP
      demonstrated strong staining. Examination of MDR1 gene polymorphisms revealed no
      correlation with P-gp expression whereas the MRP2 exon 10 G1249A polymorphism was
      associated with different MRP2 labelling. CONCLUSIONS: Our results show that
      multidrug transporters are overexpressed in DNT. This finding supports the view
      that several of these transport proteins may play an important role in the
      mechanisms of drug resistance in epileptic brain tissue.

PMID- 15581026
TI  - Extraskeletal myxoid chondrosarcoma of the jugular foramen.
AB  - OBJECTIVE: To report a case of an extraskeletal myxoid chondrosarcoma (EMC)
      arising from the jugular foramen. EMCs are tumors usually seen in the deep soft
      tissues of the extremities and are rarely seen within the intracranial cavity.
      The histological differential diagnosis includes chordoma, conventional
      chondrosarcoma and chordoid meningioma, among others. A distinguishing feature of
      EMC is their characteristic reciprocal translocation t(9;22)(q22;q12). MATERIAL:
      A 63-year-old man presented with progressive hearing loss and gait imbalance.
      Magnetic resonance imaging showed a heterogeneously enhancing 2.4 cm mass in the
      cerebellopontine angle. A right far lateral transcondylar skull base approach
      with gross total removal of the tumor was performed. Intraoperative findings
      showed that the mass appeared to arise from the glossopharyngeal nerve within the
      jugular foramen. METHOD: Histology, immunohistochemistry, and fluorescence in
      situ hybridization studies were performed. RESULTS: Histological and
      immunohistochemical studies were compatible with the diagnosis of EMC.
      Fluorescence in situ hybridization studies showed disruption of the EWS gene
      locus at 22q12 and added further support to the diagnosis. CONCLUSIONS: We report
      a rare case of EMC arising from the jugular foramen, and the diagnosis of EMC can
      be supported by confirmation of disruption of the EWS gene locus.

PMID- 15581027
TI  - Algorithm for the standardized assessment of vascular patterns in glioblastoma
      specimens.
AB  - In a recent study, the existence of distinct vascular patterns with prognostic
      impact has been described in glioblastomas. The bizarre angiogenic subtype was
      associated with shorter postoperative survival times whereas the classic
      angiogenic subtype ("microvascular sprouting"; evenly distributed branching
      capillaries in major tumor parts resembling classic angiogenesis) was associated
      with a significantly more favorable outcome. Evaluation of angiogenic subtypes of
      glioblastomas may be relevant for anti-angiogenic therapy strategies. To this
      end, a method is needed for standardized evaluation of vascular patterns in
      glioblastomas. Here, we provide a simple algorithm for the standardized
      assessment of angiogenic patterns in anti-CD34-immunostained glioblastoma
      specimens, which can be used for research and in the routine diagnostic setting.

PMID- 15581028
TI  - Co-occurrence of Wilson's disease and glioblastoma multiforme--is it a chance
      association?
AB  - We report a patient with glioblastoma multiforme who was subsequently diagnosed
      to have Wilson's disease. Immunohistochemical studies of the tumor revealed high
      (> 60%) labeling index for p53 and Rb retinoblastoma protein. Whether this
      association is like the co-occurrence of retinoblastoma and Wilson's disease due
      to possible somatic mutation in chromosome 13 needs to be explored.

PMID- 15581029
TI  - Malignant peripheral nerve sheath tumor of the spine after radiation therapy for
      Hodgkin's lymphoma.
AB  - We report the development of a malignant peripheral nerve sheath tumor (MPNST) in
      2 patients after irradiation for Hodgkin's lymphoma. Clinicians should be aware
      of this uncommon, but important fatal complication of radiation therapy. The
      first case is a 37-year-old man who was diagnosed with nodular sclerosing (NS)
      Hodgkin's lymphoma and underwent successful mantle radiation. He presented to our
      neurosurgery service with a left C6 radiculopathy 6 years later. The second case
      is a 30-year-old female diagnosed with NS Hodgkin's lymphoma. She did well with
      extensive radiotherapy until 5 years later when she developed severe right arm
      and chest pain secondary to recurrent lymphoma. After aggressive radio- and
      chemotherapy, she presented to the neurosurgery service with a right Horner's
      syndrome, right C6 radiculopathy, and weakness of her right triceps and wrist
      extensors. Both patients obtained magnetic resonance imaging revealing intradural
      extramedullary cervical nerve root associated mass lesions. Two years after
      radiation therapy for his Hodgkin's lymphoma, the first patient underwent a C6
      laminectomy at an outside institution for resection of a benign neurofibroma.
      Four years later, he underwent a posterior C5-7 laminectomy with lateral mass
      plate fusion and partial excision of a recurrent mass diagnosed as a MPNST. The
      second patient underwent a C5-6 hemilaminectomy and partial resection of a tumor
      also pathologically consistent with MPNST. We present 2 case reports of patients
      who developed neurofibrosarcomatous tumors with malignant transformation after
      undergoing radiation therapy for Hodgkin's lymphoma. Despite prompt surgical
      resection, these tumors exhibited aggressive behavior. Numerous cases of soft
      tissue tumors have been described to arise in areas of prior radiation therapy;
      however, there have been rare reports of de novo MPNST after radiation therapy,
      especially in the setting of Hodgkin's lymphoma. Postirradiation MPNST should be
      considered in the differential diagnosis of a painful, enlarging mass in a
      previously irradiated area.

PMID- 15581030
TI  - [Psychodermatology: current state of the problem].
AB  - An analysis of comorbidity of psychiatric and dermatological pathology in
      historical, epidemiological and clinical aspects is presented. Psychocutaneous
      disorders (delusional parasitosis, hypochondria circumscripta, obsessive
      compulsive disorders with self-mutilations, pathomimia) play a central role in
      systematics elaborated in the present study. The authors suggest that delusional
      parasitosis is a subtype of paranoiac psychosis (paranoia, paranoiac
      schizophrenia). Psychiatric disorders triggered by dermatological pathology were
      specified as nosogenous reactions, depressive reactions with sociophobia,
      pathologic personality development (paranoiac, sensitive, hypochondriac). Atopic
      dermatitis, eczema, urticaria, psoriasis, herpes simplex, alopecia areata,
      rosacea, etc, are regarded among dermatological psychosomatic disorders with
      psychogenic manifestation/exacerbation.

PMID- 15581031
TI  - [Postural imbalance in patients with vascular brain pathology].
AB  - Using MRI survey, 163 patients with various brain pathology of vascular genesis
      were studied. Vascular dementia according to NINDS-AIREN classification was
      diagnosed in 15% of patients. Cognitive disturbances in other patients did not
      reach a level of dementia. A control group comprised 61 subjects without rough
      structural changes on MRI and cognitive dysfunction. Motor disorders were
      estimated according to classification of J. Nutt et al. (1993), quantitative
      static changes were registered using computer stabilography. The results of the
      study showed that postural instability occurs in 100% of patients with vascular
      brain pathology. A degree of its expression elevated in direct proportion to the
      expression of cognitive disturbances, reaching a maximum in patients with
      dementia.

PMID- 15581032
TI  - [Leprous neuropathies].
AB  - The damage to the peripheral nervous system (PNS) is a marker of Micobacterium
      leprae (M. leprae) infection that develops as a result of the M. leprae invasion
      to the Schwann cells. Clinical, functional (skin-deep and stimulating
      electromyography, determination of the spreading velocity of the pulsatory wave
      along the arteries of muscle type, direct and volumetric sphingmography,
      reovasography, skinning electrotermometry) and immunological (evaluation of
      antibodies to neuroantigenes by ELISA) methods were used to study 132 patients
      with leprous neuropathy. Sensory impairment (descend of superficial sensibility,
      combination of the spotted, trunk and polyneuritic types of sensory injury),
      hypertrophy of the peripheral nerves and their painfulness by palpation were
      shown to develop at the initial stage, with the following joining of motor and
      trophic disturbances, such as amyotrophy, contractures, shortening of digits,
      trophic ulcer. Skin-deep and stimulating electromyography revealed the
      subclinical manifestation of neuromuscular system injuries in clinically normal
      muscles. A neuroantigen's entrance into the bloodstream and antibody reactions to
      them were characteristic of LN. High antibody levels, as a rule, corresponded to
      the exacerbations of leprous neuropathy, activation of leprous process, relapses
      of the disease and reactions of leprous erythema nodosum type. An association
      between specific humoral response to the antigens of the M. leprae and production
      of the antibodies to neuromarkers was found.

PMID- 15581033
TI  - [Psychogenic and somatic interactions in diabetes mellitus].
AB  - As a result of 10-year follow-up study of 250 patients with diabetes mellitus,
      type I (58) and type II (192) 4 predictable psychological crises have been
      singled out: the first one was related to reaction to the diagnosis; the second-
      to the assignment of insulin therapy; the third--to the development of diabetes
      complications and the fourth--to hospitalization and a subsequent communication
      with other, more "experienced", patients. In the progress of the disease, an
      interaction of psychogenic, somatic and personality factors caused development of
      psycho-somatic cycles (psycho-somatic balancing according to H. Baruk), which is
      realized in 3 variants: predominantly psychogenic, predominantly somatic and
      psycho-somatic.

PMID- 15581034
TI  - [Neurophysiologic and neuropathological analysis of Parkinson's disease and its
      treatment with stereotaxic method].
AB  - Complete stopping of tremor or its essential reduction have been achieved in 55
      of 66 patients with Parkinson's disease. In 3 cases, there was a fatal outcome.
      The microstructural changes of nigrostriatal, thalamus and neocortex neurons are
      presented, and biopotentials led from these structures, along with clinical and
      neurophysiological effects of electrostimulation of thalamic and subthalamic
      regions, are evaluated. The results obtained in the study are used for
      explanation of tremor mechanism.

PMID- 15581035
TI  - [Transcranial micropolarizations in combined treatment of speech and general
      psychomotor development retardation in children of the senior preschool age].
AB  - Efficiency of combined therapy with the use of transcranial micropolarization
      developed by the authors was analyzed in 30 children, aged 4-6 years, with speech
      delay and general mental impairment. In 60-80% of the cases, a high therapeutic
      effect of the new method has been achieved due to accelerated development of
      communicative behavior, speech and motor functions formation, increase of
      attention stability and improvement of perceptive and productivity processes of
      cognitive activity.

PMID- 15581036
TI  - [Placebo to antidepressant effects ratio by electroencephalographic data].
AB  - An analysis of EEG spectral characteristics of placebo effect and antidepressant
      (fluoxetine, maprotiline) monotherapy in patients with mild or moderate
      depressive episodes (ICD-10) has been conducted. Depending on clinical effects of
      placebo and antidepressants, the groups of placebo- and medication-responders/non
      responders were compared. Placebo caused both particular and similar with the
      action of a single antidepressant dose changes in spectral power of EEG bands,
      which reduced during the pharmacotherapy course. The EEG changes achieved a
      significant level mostly in placebo-responders. Differences in EEG reactions
      between medication responders and non-responders were rare and emerged at the
      stage of the placebo therapy and single antidepressant dose intake. The change of
      between-hemisphere asymmetry of alpha-rhythm low band power in the frontal brain
      regions corresponding to the increase of activation of these regions in the left
      hemisphere, was found to be characteristic of thymoleptic effect of
      pharmacotherapy.

PMID- 15581037
TI  - [Genetic counseling in the Mental Health Research Center of the Russian Academy
      of Medical Sciences].
AB  - Current concepts on the role of genetic factors in the development of
      schizophrenia and on the relative risk for this disease and spectrum disorders
      are reviewed. An analysis of the results of genetic counseling of 120 subjects
      revealed that, comparing to other mental disorders, patients with schizophrenia
      or relatives, mostly those having a schizophrenic parent (40%) or spouse (25%),
      referred more frequently for a consultation. Most of the referrals (70%) had a
      high educational level. As it was found out during the counseling, up to 20% of
      the relatives met a diagnosis of psychiatric disorders, mostly personality
      disorder (9%) and depressive state (7%). Psychological testing with personality
      inventories revealed a high level of personality abnormalities (schizoid--22%,
      hyperthymic--16% and obsessive-anxiety--4%) in 43% close relatives of patients
      seeking medicogenetic advice. The genetic counseling featured by the use of the
      comprehensive approach, basing on all obtained data (psychiatric, psychological,
      neurophysiologic etc.), that increases its accuracy and may assist families in
      taking a reasonable decision in birth planning.

PMID- 15581038
TI  - [The state and perspectives of psychiatric care in the works by A.V.
      Snezhnevskii].

PMID- 15581039
TI  - [Betaserc in the treatment of vestibular disorders in vascular dystonia
      syndrome].

PMID- 15581040
TI  - [Influence of psychotropic drugs on thrombocytes aggregation in patients with
      epilepsy].

PMID- 15581041
TI  - [The peculiarities of bulimic disorders in anorexia nervosa of endogenous
      origin].

PMID- 15581042
TI  - [Convulsions of newborns--semiotics and differential diagnosis].

PMID- 15581043
TI  - [Psychosocial factors, gender and pain].

PMID- 15581044
TI  - [A modern state of the S.S. Korsakov's alcoholic polyneurotic psychosis
      doctrine].

PMID- 15581045
TI  - Paclitaxel and gemcitabine, as first-line chemotherapy, combined with trastuzumab
      in patients with advanced breast cancer: a phase II study conducted by the
      Hellenic Cooperative Oncology Group (HeCOG).
AB  - PURPOSE: Advanced breast cancer (ABC) is an incurable disease. Standard first
      line treatment for patients with HER-2/neu overexpressing tumors includes the
      combination of the humanized monoclonal antibody trastuzumab with chemotherapy,
      mainly paclitaxel. This combination is the first to demonstrate a survival
      advantage in this group of patients. To improve on these results, we investigated
      a triplet, paclitaxel-gemcitabine-trastuzumab (TGH), in a phase II study.
      PATIENTS AND METHODS: Patients with ABC were accrued to the study. Treatment
      consisted of paclitaxel 80 mg/m2/week, gemcitabine 1000 mg/m2 every 2 weeks, and
      trastuzumab 4 mg/kg loading dose and then 2 mg/kg/week. Patients were treated on
      study for a total of 12 weeks. Response evaluation was performed at the end of
      the 12 weeks. Continuation of treatment beyond the 12 weeks was left to the
      discretion of the investigator. Primary study endpoint was response. Toxicity
      assessment and survival were secondary endpoints. RESULTS: Between November 2000
      and May 2002, 40 patients were accrued and 32 patients completed all 12 weeks of
      therapy. One patient died of septic shock during therapy. Grade III and IV
      neutropenia was seen in 12.5% of cases each. Grade III anemia was seen in two
      patients, and grade III and IV thrombocytopenia in three and two patients,
      respectively. Both paclitaxel and gemcitabine were delivered at 86% of the
      planned dose intensity. Six patients achieved a complete response (CR) and 15 a
      partial response for an overall response rate of 52.5%. An additional 25%
      demonstrated stable disease and 20% progressive disease. Median duration of
      response was 14 months. All six patients who achieved CR are still in CR for 6 to
      19 months. After a median follow up of 12.2 months, 19 patients have progressed
      and 7 have died. Median time to progression is 13.7 months, whereas median
      survival has not been reached. CONCLUSION: TGH is a well-tolerated and effective
      regimen for the first-line treatment of ABC. Randomized comparison between
      paclitaxel, trastuzumab, and triplets are warranted.

PMID- 15581046
TI  - Cardiac safety of pegylated liposomal doxorubicin (Doxil/Caelyx) demonstrated by
      endomyocardial biopsy in patients with advanced malignancies.
AB  - Although conventional doxorubicin demonstrates broad activity, its clinical use
      is limited by cardiotoxicity. A more recent analysis suggests conventional
      doxorubicin-related cardiotoxicity occurs more frequently and at lower cumulative
      doses than previously reported. Pegylated liposomal doxorubicin, designed to
      maintain or improve conventional doxorubicin activity while reducing toxicities,
      has demonstrated improved cardiac safety versus conventional doxorubicin. In this
      prospective study, we evaluated endomyocardial biopsies to determine the cardiac
      effects of pegylated liposomal doxorubicin in patients with advanced malignancies
      receiving doxorubicin-equivalent doses > or = 550 mg/m2 (including pegylated
      liposomal doxorubicin) or > or = 400 mg/m2 pegylated liposomal doxorubicin alone.
      Eight patients were enrolled, and 10 biopsy scores were obtained (two patients
      had two biopsies). Median biopsy score (Billingham scale) was 0.75 (range, 0-1.5)
      after a median pegylated liposomal doxorubicin dose of 707.5 mg/m2 and median
      total anthracycline exposure of 908.5 mg/m2. These results suggest that pegylated
      liposomal doxorubicin minimizes doxorubicin-related cardiotoxicity, even at doses
      exceeding the recommended lifetime cumulative conventional dose (450-550 mg/m2).

PMID- 15581047
TI  - Trastuzumab, paclitaxel, cisplatin, and radiation for adenocarcinoma of the
      esophagus: a phase I study.
AB  - PURPOSE: To conduct a phase I study incorporating trastuzumab with paclitaxel,
      cisplatin, and radiation for adenocarcinoma of the esophagus. METHODS AND
      MATERIALS: Patients with adenocarcinoma of the esophagus without distant organ
      metastases were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel
      50 mg/m2 weekly for 6 weeks with radiation 50.4 Gy. HER-2/neu-positive patients
      (2+/3+ by immunohistochemistry) received weekly trastuzumab at dose levels of 1,
      1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg,
      respectively. HER-2/neu-negative patients received the same chemoradiation
      without trastuzumab as a control for toxicity. Dose-limiting toxicities were
      defined as grade 3 esophageal, cardiac, or pulmonary toxicity. RESULTS: Twelve of
      36 screened patients (33%) overexpressed HER-2/neu by immunohistochemistry (seven
      3+ and five 2+). Eight of 12 patients with HER-2/neu overexpression by IHC had an
      increase in the number of HER-2/neu genes, six from amplification of the HER-2/
      neu gene and two were hypderdiploid for chromosome 17. Thirty patients were
      enrolled (12 HER-2/neu-positive and 18 HER-2/neu-negative controls). No increase
      in toxicity was seen with the addition of trastuzumab. One of 12 patients in the
      trastuzumab arm and 8 of 17 in the control arm had grade 3 esophagitis (p < or =
      .026). Mean left ventricular ejection fraction for the trastuzumab group was 57%
      before treatment and 56% after treatment. CONCLUSION: HER-2/neu is overexpressed
      in approximately one-third of esophageal adenocarcinomas. Trastuzumab can be
      added at full dose to cisplatin, paclitaxel, and radiation. Future studies of
      trastuzumab in esophageal adenocarcinoma are indicated.

PMID- 15581048
TI  - Prediction of survival for advanced cancer patients by recursive partitioning
      analysis: role of Karnofsky performance status, quality of life, and symptom
      distress.
AB  - We performed an exploratory recursive partitioning analysis (RPA) in 429
      metastatic cancer patients who had completed a Functional Assessment of Cancer
      Therapy-General (FACT-G) and a Memorial Symptom Assessment Scale-Short Form (MSAS
      SF) to define survival prognostic groups. The Cox model analysis also was
      performed. Both RPA and Cox models included Karnofsky performance status (KPS),
      age, FACT-G subscales, and MSAS-SF subscales as survival predictors. Of 429
      patients, 348 patients (81.1%) had expired at time of analysis. The median age
      was 67 years (27-89), with median length of survival of 147 days. The RPA
      identified four distinct survival groups (p < .0001) with three variables: KPS,
      physical well-being, and physical symptom distress. The most significant split
      was KPS of 50%, followed by physical well-being score of 25 and physical symptom
      distress score of 0.6. The median survival time was 29 days for patients with KPS
      < 50%; 146 days for patients with KPS > or = 50% and physical well-being < 25;
      292 days for patients with KPS > 50%, physical well-being > or = 25, and physical
      symptom distress score > 0.6; and 610 days for patients with KPS > or = 50%,
      physical well-being > or = 25, and physical symptom distress score < or = 0.6.
      The Cox model found, in addition to KPS (p < .0001) and physical well-being (p =
      .08), different predictors: psychological symptom distress (p = .0007), global
      distress index (p = .02), and age (p < .0001). We concluded that the KPS, quality
      of life, and symptom distress scores can be combined to define prognostic groups.
      Such models may be helpful for clinical decision making.

PMID- 15581049
TI  - Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in
      metastatic pancreatic adenocarcinoma: a phase I and II trial.
AB  - BACKGROUND: This study evaluates the maximum tolerated dose (MTD) and activity of
      mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic
      adenocarcinoma, previously treated with gemcitabine-containing chemotherapy.
      PATIENTS AND METHODS: Patients with less than 76 years, Karnofsky performance
      status > or = 60, and adequate bone marrow, kidney, and liver function were
      eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1,
      docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks.
      Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30
      and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was
      defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4
      thrombocytopenia, nausea and vomiting, or diarrhea, grade > or = 3
      nonhematological toxicity, or failure to recover to grade < or = 1 toxicity by
      day 43, occurring during the first cycle of chemotherapy. RESULTS: Between
      September 2001 and October 2002, 15 eligible patients, three of whom had been
      previously treated with two lines of chemotherapy, received 33 cycles of MDI.
      Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue,
      diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in
      2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3
      level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen
      patients were assessable for response. No objective response was observed among
      patients treated with MTD or higher doses. Three patients had stable disease; all
      other patients had progressive disease. The median time to tumor progression and
      median survival was 1.7 and 6.1 months, respectively. CONCLUSION: The MTD was
      mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8.
      This regimen is inactive in metastatic pancreatic cancer.

PMID- 15581050
TI  - Papilloma and polyoma DNA tumor virus sequences in female genital tumors.
AB  - Human papillomaviruses (HPVs) and BKV, JCV, and SV40 polyomaviruses (PYVs) are
      oncogenic viruses associated with different human tumors. Our aim was to
      determine if PYV and HPV sequences could be detected in human genital tumors. HPV
      types 6b, 11, 16, and 18 and PYV were investigated in 22 genital tumor samples
      and the corresponding adjacent normal tissues, by PCR and filter hybridization.
      HPV and PYV sequences were also searched in six sperm fluid and four peripheral
      blood cell (PBC) samples. HPV-16 sequences were revealed in 7 of 14 cervical
      tumors and 1 of 1 vaginal adenocarcinoma, whereas 1 of 14 cervical carcinoma
      tested positive for HPV-18. Interestingly, each normal cervical tissue
      surrounding the neoplasm obtained from the same patient was positive for HPV type
      16 and -18 with the same prevalence detected in tumors. BKV sequences were found
      in 9 of 14 cervical tumors, 1 of 7 vulvar tumors, and 1 of 1 adenocarcinoma, but
      also in normal tissues from cervix (13 of 14), vulva (6 of 7), sperm fluid (5 of
      6) and PBC (3 of 4) samples. SV40 sequences were detected in 1 of 14 normal
      cervical tissue, 2 of 6 sperm fluids and 1 of 4 PBCs. None of the samples were
      JCV positive. To our knowledge, this is the first investigation reporting on the
      simultaneous association of both HPV and PYV with human genital tumors. These
      results suggest that PYV, together with HPV, may be involved as a cofactor in the
      onset/progression of human genital tumors, and raise the possibility that PYV act
      synergistically with HPV to enhance their pathogenicity in vivo. In addition, HPV
      and PYV may complement each other in infecting human genital tissues.

PMID- 15581051
TI  - Herceptin and gemcitabine for metastatic pancreatic cancers that overexpress HER
      2/neu.
AB  - PURPOSE: To determine the response rate and toxicities of Herceptin and
      gemcitabine for patients with metastatic pancreatic adenocarcinomas that
      overexpress HER-2/neu. METHODS AND MATERIALS: Patients with metastatic pancreatic
      cancer with 2+/3 + HER-2/neu expression by immunohistochemistry were eligible.
      Patients received gemcitabine, 1 g/m2/week, for 7 of 8 weeks followed by 3 of
      every 4 weeks, and Herceptin, 4 mg/kg loading dose, followed by 2 mg/kg/week.
      RESULTS: Screening logs demonstrated the rate of HER-2/neu overexpression was
      16%. Thirty-four patients were enrolled. Thirty patients (88%) had pancreatic
      cancers with 2+ overexpression and 4 patients (12%) had 3+ overexpression.
      Toxicity was similar to gemcitabine alone. Confirmed partial responses were
      observed in 2 of 32 patients (6%). Thirteen of 32 patients (41%) had either a
      partial response or a >50% reduction in CA 19-9. The median survival for all 34
      patients was 7 months, and the 1-year survival was 19%. CONCLUSION: The response
      rate of Herceptin and gemcitabine is similar to gemcitabine alone. The 7-month
      median survival in patients with metastatic pancreatic cancer suggests there may
      be a modest benefit for some patients. Infrequent HER-2/neu overexpression limits
      the role of targeting the HER-2/neu gene and prevents definitive conclusions on
      the addition of Herceptin to gemcibine for patients with pancreatic cancer.

PMID- 15581052
TI  - Capecitabine: fixed daily dose and continuous (noncyclic) dosing schedule.
AB  - BACKGROUND: Oral fluoropyrimidines are presumed to emulate a parenteral
      continuous low-dose infusion delivery of the drug and the commonly used schedule
      is a 14 day on, 7 day off cycle at a total daily dose of 2500 mg/m2 dose. There
      is a substantial incidence of diarrhea and hand/foot syndrome with this dose
      schedule. OBJECTIVE: To retrospectively analyze a clinical experience with a
      fixed-unit daily dose of capecitabine employed continuously (open ended without
      cycling) as a single agent, in combination with other agents, or combined with
      radiation to determine the drug tolerability with regard to stomatitis, diarrhea,
      and hand/foot syndrome, compared with the "standard" dose schedule. METHOD: Fifty
      patients received 58 courses of continuous fixed daily dose capecitabine as a
      single agent (19 courses), combination with weekly irinotecan (15 courses);
      combined with 24-hour 5-fluorouracil (5-FU) infusion weekly (5 courses), combined
      with radiation (3 courses), or with other chemotherapy (16 courses). A fixed
      divided daily dose of 1500 or 2000 mg was administered for an open-ended period
      of time designed to deliver 10 weeks of continuous administration. Incidence and
      time to adverse event (toxicity) was determined for each course. RESULTS:
      Capecitabine was administered continuously for 4 weeks to 8 months with a median
      of 3 months. Seven of 50 patients (14%) experienced grade 2 or 3 toxicity;
      hand/foot syndrome, 4 (8%); stomatitis plus diarrhea (grade 2), 1%; and diarrhea
      alone, 3 (6%). Four of the 7 patients developing toxicity received concomitant
      weekly 24-hour 5-FU and 3 patients received concomitant CPT 11 (1), doxil (1), or
      taxane (1). None of the patients on single-agent capecitabine (19) developed
      toxicity of any grade. The total daily dose of capecitabine was 830 to 1250
      mg/m2. The maximum dose intensity of the continuous fixed-dose schedule is 8750
      mg/m2/week compared with 11,666 mg/m2/week for the standard dose and schedule
      (2500 mg/m2/day for 14 days every 21 days). CONCLUSION: Capecitabine administered
      as a continuous daily fixed dose has a low toxicity profile and can be
      administered in conjunction with other therapies relatively easily. This schedule
      provides for convenience and simplicity, and therapeutic effects are demonstrated
      even at low doses. The dose intensity of the noncycling continuous regimen is
      approximately 20% less than the standard cycling 2 weeks on every 21-day
      schedule.

PMID- 15581053
TI  - Raloxifene rebound regression.
AB  - The first case of clinical remission of metastatic breast after the withdrawal of
      raloxifene is reported. A postmenopausal woman was treated for stage II breast
      cancer with a modified radical mastectomy and adjuvant cyclophosphamide,
      doxorubicin, and 5-flurouracil followed by tamoxifen for 5 years. One year
      following the cessation of tamoxifen, osteopenia was noted and raloxifene was
      begun. Two years following the start of raloxifene, supraclavicular adenopathy
      and lung metastases developed, which regressed after discontinuation of
      raloxifene. Although raloxifene is not frequently given to women with previous
      breast cancer, increasing use in osteopenic women may lead to cancer developing
      in these raloxifene-treated women; this despite the major reduction in the
      incidence of breast cancer in raloxifene-treated versus placebo-treated women. A
      clinically significant response to the withdrawal of a hormone, used either for
      the treatment of breast cancer or for some other reason, is not a rare event, and
      the therapeutic usefulness of observation only for a rebound regression is a
      frequently overlooked strategy in the treatment of breast cancer.

PMID- 15581055
TI  - Ovarian cancer: review of the National Institute for Clinical Excellence (NICE)
      guidance recommendations.
AB  - The National Institute for Clinical Excellence (NICE), established in 1996 as a
      special Health Authority for England and Wales, provides the United Kingdom
      medical community with robust and reliable guidance on current "best practices"
      in medicine. Based on analyses of clinical efficacy, safety, and cost
      effectiveness, clinical guideline recommendations are developed in an attempt to
      standardize treatment of various diseases and medical conditions. To date, NICE
      has issued guidance for the use of three chemotherapeutic agents in the treatment
      of ovarian cancer: paclitaxel, topotecan, and pegylated liposomal doxorubicin.
      NICE guidance recommends surgery and adjuvant chemotherapy with
      paclitaxel/platinum combination therapy or platinum therapy alone as first-line
      treatment for ovarian cancer. NICE has also issued guidance recommending the use
      of topotecan or pegylated liposomal doxorubicin as second-line agents for the
      treatment of women with relapsed or refractory disease. Accounting for all
      available data, NICE guidance supports the appropriate roles of paclitaxel,
      topotecan, and pegylated liposomal doxorubicin in the treatment of advanced
      ovarian cancer.

PMID- 15581054
TI  - Differential effects of antiangiogenic compounds in neovascularization, leukocyte
      recruitment, VEGF production, and tumor growth in mice.
AB  - Angiogenesis and inflammation play critical roles in tumor growth. Using an in
      vivo tumor model, we report that thalidomide (100 mg kg(-1)day(-1)) or
      clotrimazole (120 mg kg(-1) day(-1)), inhibit blood vessel formation (determined
      by hemoglobin content), leukocyte recruitment [myeloperoxidase (MPO) activity; N
      acetylglucosa-minidase (NAG) activity], and vascular endothelial growth factor
      production. Inhibition of angiogenesis ranged from 35% to 65%. Clotrimazole was
      the most potent antiangiogenic compound and the agent capable of inhibiting tumor
      growth. Thalidomide was able to reduce the inflammatory reaction (MPO and NAG
      activities) by 50% to 70%, but was unable to delay tumor development. These
      results suggest that for this type of solid tumor the degree of
      neovascularization, rather than inhibition of inflammatory cell recruitment, is a
      determinant factor in tumor development. As the contribution of angiogenesis and
      inflammation to cancer progression vary markedly among different tumor types, it
      may be relevant to consider these factors in cancer therapy using
      antiangiogenesis/antiinflammatory approaches.

PMID- 15581056
TI  - Cosmic radiation exposure and cancer risk among flight crew.
AB  - Nearly 20 epidemiologic or related studies of cancer incidence and mortality have
      been published during or since 2000, with several reporting increased risks of
      female breast cancer among flight attendants and melanoma among both pilots and
      cabin crew. Occasionally, excesses of other cancers have been observed, but not
      consistently. Although the real causes of these excess cancer risks are not
      known, there is concern that they may be related to occupational exposures to
      ionizing radiation of cosmic origin. It is possible that confounding risk factors
      may partially or totally explain the observed relationships, but several
      investigations are beginning to address lack of past adjustment for reproductive
      factors and sun exposure with improved study designs. With progress in aviation
      technology, planes will fly longer and at higher altitudes, and presumably the
      number of flights and passengers will increase. To respond responsibly to the
      real and perceived risks associated with flying, more extensive data are needed,
      but special efforts should be considered to ensure new projects can genuinely add
      to our current knowledge.

PMID- 15581057
TI  - Tailored chemotherapy for colorectal cancer: a new approach to therapy.
AB  - The treatment of colorectal cancer has advanced over the past several years with
      the introduction of several active agents. Determining which patients to treat
      with chemotherapy and choosing optimal treatment would allow practioners to
      maximize the benefit of chemotherapy. Several prognostic and predictive markers
      have been identified and include oncogenes, tumor suppressor genes, genes
      involved in angiogenic and apoptotic pathways and cell proliferation, and those
      encoding targets of chemotherapy. Specifically, prognostic markers include
      deletion of 18q (DCC), p27 and microsatellite instability. Predictive markers are
      those that may determine efficacy of drugs used in colorectal cancer such as
      fluropyrimidines and oxaliplatin. Alterations in gene expression, protein
      expression and polymorphic variants in genes encoding thymidylate synthase,
      dihydropyrimidine dehydrogenase, and thymidine phosphorylase and excision repair
      cross-complementing genes (ERCC1) may be useful as markers for clinical drug
      response, survival and host toxicity. The integration of these prognostic and
      predictive markers would allow individualized treatment for patients, maximizing
      therapeutic effect and minimizing exposure to toxicity.

PMID- 15581058
TI  - AIDS-related cancer in the era of highly active antiretroviral therapy (HAART): a
      model of the interplay of the immune system, virus, and cancer. "On the offensive
      -the Trojan Horse is being destroyed"--Part A: Kaposi's sarcoma.
AB  - The introduction of highly active antiretroviral therapy (HAART), aimed at
      controlling human immunodeficiency virus (HIV), has been associated with a
      dramatic decrease in the incidence of acquired immunodeficiency syndrome-Kaposi's
      sarcoma (AIDS-KS) and the clinical manifestations of KS appear to be less
      aggressive. The pathogenesis of AIDS-related KS is related to a system of
      cytokines (e.g., interleukin-6) driven by autocrine and paracrine loops. More
      recently, human herpesvirus 8 (HHV-8), was discovered to be the putative
      etiological agent of this disease. This virus encodes several unique open reading
      frames that are homologs of human cellular proteins involved in cellular
      regulations, cell proliferation, apoptosis, and immune regulation. The treatment
      of this disease depends on whether it is "limited" disease or "extensive"
      disease. For "limited" disease, local therapy or non-bone marrow suppressive
      agents should be used. For "extensive" disease, new chemotherapeutic agents, such
      as liposomal anthracycline, which are active and have little adverse reactions,
      are indicated. The control of HIV infection continues to be essential. Knowledge
      of the pathogenesis of the disease has led to the development of novel treatment
      strategies, aimed at the inflammatory or angiogenesis cytokines necessary for
      growth or at HHV-8 as the target of therapy.

PMID- 15581059
TI  - AIDS-related cancer in the era of highly active antiretroviral therapy (HAART): a
      model of the interplay of the immune system, virus, and cancer. "On the offensive
      -the Trojan Horse is being destroyed"--Part B: Malignant lymphoma.
AB  - The impact of highly active antiretroviral therapy (HAART) on the incidence of
      non-Hodgkin's lymphoma was less obvious initially, although primary central
      nervous system lymphoma (PCNSL) has dropped precipitously since the introduction
      of HAART. The pathogenesis of acquired immunodeficiency syndrome-related lymphoma
      is multifactorial. Epstein-Barr virus plays a significant role in these diseases,
      especially Burkitt lymphoma and PCNSL. Data regarding the effect of HAART on the
      natural history and treatment outcomes of these malignancies are emerging. The
      possibility of direct and indirect roles of human immunodeficiency virus in the
      carcinogenesis suggests that antiretroviral therapy may be an important component
      of the treatment for these malignancies. The simultaneous administration of HAART
      and chemotherapy does not appear to significantly alter the toxicity profile,
      although the information with respect to the interaction of HAART and
      chemotherapy is limited. The use of biological agents, for example, monoclonal
      antibody against CD-20, is being explored to improve the clinical outcome of this
      disease.

PMID- 15581060
TI  - Pain and its management in patients with cancer.

PMID- 15581061
TI  - Allocation or misallocation of limited medical resources.
AB  - Very small premature babies are now kept in neonatal intensive care units for
      many months to give them a chance at near normal life, but at a cost of up to
      dollars 1 million. Is that a proper allocation of our finite medical resources
      (personnel, equipment, supplies, and other necessities) for premies? Or is such
      action a misallocation of these resources? Both sides of the argument have
      positive and negative merit. A final philosophical statement is that each human
      created in the image of God has supreme value. It is it the obligation of fellow
      humans and society in general to preserve and dignify human life and to care for
      the total needs of individual citizens to enable them to be healthy and
      productive members of society. This general principle should help individual
      physicians make proper microallocation life and death decisions for individual
      patients and assist governmental bodies responsible for making macroallocation
      decisions concerning the short- and long-term needs and priorities of the
      population as a whole. All such decisions should be guided by the basic ethical
      principles of beneficence, nonmaleficence, autonomy, and justice. However, these
      principles may at times conflict. For example, if the autonomous rights of the
      patient conflict with the justice appeals of the community or if beneficence to
      an individual patient conflict with the needs of another patient, can we deny
      health care services? By what criteria (merit, potential, effort, achievement,
      age)? These are difficult if not impossible questions to answer, but they pertain
      to the topic of this commentary on the allocation of limited medical resources,
      which is meant to raise the sensitivity of the reader to the complexity of the
      problem and to raise ethical questions, which are not easily answered or dealt
      with.

PMID- 15581062
TI  - Editorial on a phase I study on combined modality therapy in esophageal cancer.

PMID- 15581063
TI  - NICE guidelines for ovarian cancer: recommendations versus standard care.

PMID- 15581064
TI  - Chemotherapeutic response with single agent gemcitabine in metastatic Bellini
      duct tumor.

PMID- 15581065
TI  - The biological functions of beta3 integrins.
AB  - Integrins comprise a large family of alphabeta heterodimeric cell-surface
      receptors that are found in many animal species. They are expressed on a wide
      variety of cells. There are two members in the beta3 integrin family: alphaIIb
      beta3 and alpha(v)beta3. This class of adhesion receptors mediates cell-cell and
      cell-extracellular matrix interactions. Dysregulation of the beta3 integrins is
      involved in the pathogenesis of many diseases (including cancer) and in
      transplant rejection. Integrins also play a key role in many virus infectious
      cycles. In this paper the biological functions of the beta3 family are reviewed,
      with particular interest in its role in cancer progression and metastasis.

PMID- 15581066
TI  - The frequency of alleles of the Pro12Ala polymorphism in PPARgamma2 is different
      between healthy controls and patients with type 2 diabetes.
AB  - The aim of this initial case-control study was to determine the association
      between common Pro12Ala polymorphism in the PPARgamma2 gene and type 2 diabetes
      in the Czech Republic. Furthermore, the effect of this polymorphism on phenotypic
      characteristics and on levels of lipids (total cholesterol, HDL-cholesterol, LDL
      cholesterol and triglycerides) was studied. One hundred thirty-three patients
      with type 2 diabetes and 97 control subjects were investigated. PCR and RFLP
      analysis were used for identification of individual genotypes. In the group of
      patients, three samples (2.26%) were identified as homozygous for the Ala/Ala
      genotype and 99 samples (74.44%) were homozygotes for the Pro/Pro genotype.
      Thirty-one samples (23.31%) were identified as Pro12Ala heterozygous. In the
      control group, six samples (6.19%) were homozygous for the Ala/Ala genotype and
      61 samples (62.89%) were homozygotes for the Pro/Pro genotype. Thirty samples
      (30.93%) were identified as Pro12Ala heterozygous. The allele frequency for the
      Ala allele was lower in the type 2 diabetic group than in the control group
      (13.91% vs. 21.43%, P = 0.022). There was no difference (at P < 0.05) between the
      phenotypic characteristics (BMI, sex) studied in the group of patients according
      to the Pro12Ala genotype. There was no significant effect of the Pro12Ala
      polymorphism on lipid levels.

PMID- 15581067
TI  - A Gly482Ser polymorphism of the peroxisome proliferator-activated receptor-gamma
      coactivator-1 (PGC-1) gene is associated with type 2 diabetes in Caucasians.
AB  - The PGC-1 gene has been implicated in the regulation of several genes controlling
      energy metabolism. The prevalent Gly482Ser polymorphism of the PGC-1 gene has
      been shown to be associated with type 2 diabetes in some but not all studies. The
      aim of this study was to analyse whether the Gly482Ser variant is a risk factor
      for development of type 2 diabetes in Slovene population (Caucasians). Genotyping
      of the Gly482Ser polymorphism was performed for 545 subjects: 305 patients with
      type 2 diabetes and 240 non-diabetic controls. The Gly482Ser genotype
      distribution in patients with type 2 diabetes (AA = 11.5%, AG = 42.3%, GG =
      46.2%) differed from genotype distribution in non-diabetic controls (AA = 6.3%,
      AG = 46.3%, GG = 47.5%), and the AA genotype was associated with 1.9-times
      increased risk of type 2 diabetes (95% confidence interval 1.0-3.6; P = 0.036).
      In conclusion, we suggest that the AA genotype of the Gly482Ser polymorphism of
      the PGC-1 gene should be considered as a risk factor for the development of type
      2 diabetes in Caucasians.

PMID- 15581068
TI  - Repression of the melanocyte-specific promoter of the microphthalmia-associated
      transcription factor by the adenoviral E1A 12S oncoprotein.
AB  - Melanocytes express MITF, which is crucial for the development of the melanocyte
      lineage and is overexpressed in malignant melanomas. Adenoviral E1A protein
      expressing melanocytes are unpigmented, with the expression of MITF being
      silenced. We tested here a direct repression of the melanocyte-specific MITF
      promoter by E1A and its mutants. We found that the extreme N-terminus and
      conserved region 1 are required for repression. In contrast, the motif in
      conserved region 2 (a.a. 122-126), as well as amino acids 26-35 at the N
      terminus, are not necessary. As these two later motifs mediate E1A binding to the
      retinoblastoma protein or to the transcriptional co-activator TRRAP,
      respectively, and are important for transformation by E1A in cooperation with
      other oncogenes, the results suggest that the transformation-defective E1A can
      still efficiently repress the MITF promoter. The CREB binding motif-mutated
      promoter had lower activity, but was also repressed by the same E1A mutants in
      human melanoma cells. The E1A protein is known to also exert an antitumour
      activity, which is associated with its transcription repression function and the
      ability to induce apoptosis, and is a potential antimelanoma agent. Since recent
      data suggest that MITF may be a survival factor for melanoma cells, the E1A
      mutants described here might constitute a good targeting agent for antimelanoma
      therapy.

PMID- 15581069
TI  - Non-adherent bone marrow cells are a rich source of cells forming bone in vivo.
AB  - Syngeneic, allogeneic and xenogeneic (rat) freshly isolated bone marow cells +
      stromal cell cultures maintained in vitro for 10-30 days, as well as non-adherent
      cells removed from these cultures on 3rd-4th day were injected into the kidney
      parenchyma of mice, immunosuppressed with hydrocortisone. In syngeneic grafts the
      immunosuppression was omitted. In all transplant systems bone tissue was formed
      inside the kidney with 20% to 32% variation. Bone produced by allogeneic and
      xenogeneic cells is subject to rejection when immunosuppression ceases, as the
      bone formed is of donor origin. The "floating" cells, regardless of the
      transplant system, normally discarded during media replacement, turned out to be
      efficient bone producers. This notion is of practical implication when bone
      marrow cells are used for bone healing.

PMID- 15581070
TI  - Iontophoretic enhancement of leuprolide acetate by fatty acids, limonene, and
      depilatory lotions through porcine epidermis.
AB  - The effect of chemical enhancers (e.g., fatty acids, limonene, depilatory
      lotions) and iontophoresis was investigated on the in vitro permeability of
      leuprolide acetate through porcine epidermis. Franz diffusion cells and Scepter
      iontophoretic power source were used for the percutaneous absorption studies.
      Anodal iontophoresis was performed at 0.2 mA/cm2 current density. Fatty acids
      used were palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1),
      linoleic (C18:2), and linolenic (C18:3) acids. The passive and iontophoretic flux
      were significantly (p < 0.05) greater through fatty acids-treated porcine
      epidermis in comparison to the control (untreated epidermis) for leuprolide
      acetate. The passive and iontophoretic permeability of leuprolide acetate
      increased with increasing number of cis double bonds. Among the fatty acids
      tested, linolenic acid (C18:3) exhibited the maximum permeability of leuprolide
      acetate during passive (51.42 x 10(-4) cm/hr) and iontophoretic (318.98 x 10(-4)
      cm/hr) transport. The passive and iontophoretic flux of leuprolide acetate were
      significantly (p < 0.05) greater through the limonene and depilatory lotion
      treated epidermis in comparison to their respective control. In conclusion,
      iontophoresis in combination with chemical enhancers synergistically increased (p
      < 0.05) the in vitro permeability of leuprolide acetate through porcine
      epidermis.

PMID- 15581071
TI  - Two-phase melt systems of ibuprofen for enhanced membrane permeation.
AB  - A novel method to convert S- and racemic (RS-) ibuprofen (Ibu) into an oily state
      at ambient temperature (25 degrees C) was developed. Using menthol and aqueous
      isopropanol (IPA) as melting point depressing agents, the two-phase melt systems
      (TMSs) of Ibu consisting of a homogeneous oily phase and a homogeneous aqueous
      phase were obtained. In TMS with a high S-Ibu: menthol ratio and a low IPA
      content, the oily phase primarily consisted of Ibu and menthol, whereas the
      majority of the aqueous phase was IPA and buffer. Using this method, the S-Ibu
      concentration in the oily phase reached as high as 70% (w/w). The compositional
      phase diagram was obtained using a titration method to study the relationship
      between the melting states of the solid components and system composition. S- and
      RS-Ibu showed different phase diagrams, and the maximum concentration of S-Ibu
      measured in the oily phase of TMS was much greater than that of RS-Ibu. The
      permeation study of a series of TMS and non-TMS systems showed that S-Ibu
      penetrated through shed snake skin faster than RS-Ibu, and the contents of IPA
      and menthol significantly affected the permeation rates of ibuprofen across shed
      snake skin, which may be attributed to the higher lipophilicity, and thus, higher
      solubility of S-Ibu in the skin than RS-Ibu. Such results support the use of S
      Ibu TMS for topical formulation development.

PMID- 15581072
TI  - Particle size distributions of inert spheres and pelletized pharmaceutical
      products by image analysis.
AB  - Image analysis was used to measure particle size distributions (PSDs) of
      ensembles of 425 to 1400 microm-size materials. Repeatability of a measurement,
      suitable sample sizes, and methods of sampling were assessed. Two lots of inert
      spheres were compared prior to drug layering in a Glatt GPCG-5 rotor. The
      differences in PSD in the starting materials were reflected in the rotor
      granulated products. Such detailed information was not available from sieving
      with U.S. standard wire mesh sieves. The products from the rotor process were
      polymer-coated in a Wurster process in a Glatt GPCG-3, 4-in. Wurster. The
      resolution of the technique was sufficient to measure differences in diameter
      equating to 4-microm coat thickness, which resulted from applying 2% polymer coat
      weight. The utility of the technique for monitoring commercial scale processes
      was demonstrated by measuring diameter after layering drug onto nonpareils in a
      Glatt RG-150 rotor, and by measuring the diameter after application of a polymer
      solution in a Glatt 46-in. Wurster coating process. The similarity of samples
      removed from the sample port in situ and samples from the batch suggested that
      processes in the fluid bed are intensively mixed and inherently random.

PMID- 15581073
TI  - Optimization of formulation parameters for the preparation of flutamide liposomes
      by 3(3) factorial 26-term logit model.
AB  - This study deals with the study of the optimization of the volume of organic
      phase (X1), the volume of aqueous phase (X2), and the drug:phosphotidylcholine
      (PC): cholesterol (Chol) molar ratio (X3) using 3(3) factorial 26-term logit
      model to maximize the Flutamide absorption at the target site in the treatment of
      prostatic cancer by maximizing the entrapment of Flutamide (FLT) in the
      preparation of FLT liposomes. FLT liposomes are expected to be an excellent
      carrier for FLT to the prostatic cancer site based on the use of liposomes with
      other drugs. A 3(3) factorial 26-term logit model for coded factors X1, X2, and
      X3 is used to develop a second-order response surface regression equation for
      predicting percent entrapment efficiency (%EE) for FLT. In turn, the regression
      equation is used to develop contour plots that show the %EE is maximized at the
      level of 1:15:2 of the drug: PC: Chol molar ratio with the volume of organic
      phase (chloroform: methanol) (1:2) at 5 mL and the volume of distilled water at
      1.5 mL.

PMID- 15581074
TI  - Complexation between PVP and Gantrez polymer and its effect on release and
      bioadhesive properties of the composite PVP/Gantrez films.
AB  - Complexation between poly(methyl vinyl ether-maleic anhydride) copolymer (Gantrez
      AN 169) and polyvinylpyrrolidone (PVP K-90D) in aqueous solutions were
      investigated using a viscometric method and Raman spectroscopy. The composite
      films with different weight ratios of PVP to Gantrez were prepared in the
      presence of N-methyl-2-pyrrolidone. The release profiles of diclofenac sodium
      (DS) from these films were determined and the bioadhesive properties measured. An
      interpolymer complex was formed through hydrogen bonding between the carbonyl
      groups of PVP and the hydroxyl groups of Gantrez. The formation of interpolymer
      hydrogen bonds reduced the interaction of the polymers with water molecules, thus
      resulting in a lower solubility of the complex in water and a further retarded
      release of DS from the composite films. The interpolymer complexation was also
      found to increase the bioadhesive properties of the composite films to a silicone
      elastomer substrate. The complexation of PVP and the Gantrez copolymer in the
      composite films was a critical factor affecting the release of DS from the films
      and the bioadhesive properties of the films.

PMID- 15581075
TI  - Effect of a change in crystal polymorph on the degree of adhesion between
      micronized drug particles and large homogenous carrier particles during an
      interactive mixing process.
AB  - This study reports the effect of a change in crystal form on the quality of
      interactive mixtures prepared with homogenous sugar beads and the three
      polymorphs of chloramphenicol palmitate (CAP). Six mixtures containing micronized
      CAP polymorph powder (0.5%) and sugar beads (99.5%) were mixed in a Turbula mixer
      at 27 rpm or 54 rpm for 2.5, 5, 10, or 20 min. Three of the six mixtures was
      screened to remove the unmixed drug powder. The content uniformity (CV %) of the
      three screened and three unscreened mixtures was determined by determining the
      variation in drug content of 10 randomly taken samples from each mixture.
      Comparison of the amount of drug screened and the content uniformity of the
      mixtures showed that at short mixing times and 27 rpm and longer mixing times of
      10 and 20 min at 54 rpm, the three crystal forms formed interactive mixtures with
      statistically the same content uniformity. In contrast at 54 rpm and mixing for 5
      min and shorter, form A formed less homogeneous interactive mixtures compared
      with forms B and C. Consistently at both mixing speeds a larger amount of form A,
      compared with forms B and C, was screened from the mixtures. The results showed
      that the affinity between forms B and C and the carrier sugar beads is higher
      than that between form A and the sugar beads. Therefore, changing the crystal
      form of a drug influences the affinity between the drug and a carrier when
      preparing interactive mixtures.

PMID- 15581076
TI  - Biodegradation behavior of gellan gum in simulated colonic media.
AB  - The objective of this investigation was to test the biodegradability of gellan
      gum in the presence of galactomannanase in order to explore its suitability for
      the development of colon-specific controlled delivery systems. Gellan beads
      containing azathioprine (AZA) were prepared by ionotropic gelation in the
      presence of Ca2+ ions and were coated with an enteric polymer, Eudragit S-100.
      The effects of the simulated colonic fluid (SCF, pH 7.4 phosphate buffer)
      containing 15 mg/mL of galactomannanase on the in vitro release profiles of
      uncoated and enteric-coated beads were investigated, and the morphological
      changes in the structure of uncoated beads were assessed by scanning electron
      microscopy (SEM). In addition, 1% solution of deacetylated gellan gum was
      prepared and several aliquots of the resulting solution were evaluated
      rheologically to determine the concentration- and time-dependent effects of
      galactomannanase. Based on the percent drug released at 2 h, approximately 10%
      greater amount of drug was released in the SCF containing galactomannanase when
      compared with the enzyme-free dissolution medium. Results of rheological studies
      demonstrated that effects of galactomannanase on the viscosity of gellan gum
      solution are concentration-dependent rather than time-dependent. A significant
      decrease in the viscosity was noted in the presence of galactomannanase at a
      concentration of 15 mg/ mL, indicating that the polysaccharide degraded in an
      enzymatic reaction. SEM micrographs showed a distinct disruption of the polymeric
      network in the SCF. Overall, the results suggest that gellan gum undergoes
      significant degradation in the presence of galactomannanase which in turn
      facilitates the drug release from beads in the SCF in a controlled manner, thus
      approving the suitability of gellan gum as a carrier for controlled colonic
      delivery.

PMID- 15581077
TI  - Particle formation and capture during spray drying of inhalable particles.
AB  - An investigation of the spray drying process is made in great detail regarding
      particle formation and capture efficiency with focus on the production of
      inhalable particles. Mannitol was spray dried as model substance and the spray
      dried products were characterized. The resulting products consisted of smooth
      spheres with a volume median diameter of 2.2-5.5 microm, and narrow size
      distributions. The investigation was performed in pilot scale of sufficient size
      to draw general conclusions and make some recommendations. It has been shown that
      the size of particles is decreased when the feed concentration is decreased, the
      nozzle gas/feed flow mass ratio increased, and the droplet size decreased. The
      collection efficiency of the cyclone device used in this study was shown to have
      a cut-off of 2 microm, i.e., 50% of the particles less than 2 microm are not
      captured. The data reported indicate that the majority of the single particles
      formed here, <5 microm, arise from single droplets (of about 10 microm) and are
      solid, nonporous particles.

PMID- 15581078
TI  - Effect of processing on Celecoxib and its solvates.
AB  - Pharmaceuticals mostly exist in crystalline form and exhibit the phenomenon of
      differential crystal packing and configurational arrangements of molecules,
      called polymorphism. Pharmaceutical processing by introducing significant amount
      of stress alters the molecular interactions in the system engendering polymorphic
      transformations. The energy supplied by these processing steps tends to overcome
      the energy barriers between different solid-state forms, thus yielding
      undesirable changes in the physicochemical and material characteristics of drugs
      or their dosage forms. Therefore, the role of these unit processes in solid-state
      transformations must be cautiously studied and if required appropriate controls
      should be used to monitor such events. The present study was aimed at studying
      the effect of major energy imparting pharmaceutical unit processes, like size
      reduction, wet granulation, consolidation, and compression on solid-state
      transformation of Celecoxib, a selective cyclooxygenase-II inhibitor and its N,N
      dimethyl acetamide and N,N-dimethyl formamide solvated forms. A qualitative
      estimation of crystal transformation in processed samples was performed using
      DSC, microscopy, FTIR spectroscopy, and XRPD. FTIR was also applied for the
      development of a quantification method to find the percentage of transformation
      in N,N-dimethyl acetamide solvated form during compression.

PMID- 15581079
TI  - Controlled porosity osmotic pumps of highly aqueous soluble drug containing
      hydrophilic polymers as release retardants.
AB  - Controlled porosity osmotic pumps (CPOPs) are devoid of delivery orifice to
      release core contents and essentially possess pore-forming agent(s) in coating
      composition. When the pump comes in contact with aqueous media, pore-forming
      agent(s) generate pores through which core contents are delivered. Diltiazem
      hydrochloride (DLTZ) is a freely water-soluble drug and the release rates of DLTZ
      are higher from oral osmotic pumps including CPOPs, in which the drug release is
      controlled by concentration of pore-forming agents. The effect of appropriate
      concentration of hydroxypropyl methyl cellulose and sodium carboxy methyl
      cellulose mixture on the release of DLTZ from CPOPs was studied. In vitro drug
      release profiles were compared with that of different marketed controlled release
      formulations and statistically analysed to examine the suitability of CPOP for
      twice or once daily administration. Dissolution models were applied to drug
      release data in order to establish the mechanism of drug release and kinetics.
      Drug release from the CPOPs was effectively modified with the concentration of
      pore-forming agent in membrane and concentration of hydrophilic polymers in the
      core. CPOPs showed minimum 65% of consistent DLTZ release at 16 h. Statistical
      analysis confirmed that with an increase in the amount of hydrophilic polymers
      release rate decreased. Drug release from the systems follows Hixson-Crowell cube
      root model and mechanism of release follow non-Fickian diffusion.

PMID- 15581080
TI  - Dissolution rate enhancement by adsorption of poorly soluble drugs on hydrophilic
      silica aerogels.
AB  - The aim of this work is to evaluate the feasibility of hydrophilic silica
      aerogels as drug carriers and to investigate the influence of the aerogels
      properties on the release rate of poorly water-soluble drugs. Hydrophilic silica
      aerogels of different densities were loaded with two model drugs, ketoprofen and
      griseofulvin, by adsorption from their solution in supercritical CO2. It is
      demonstrated that up to 30 wt% of ketoprofen and 5.4 wt% of griseofulvin can be
      deposited on hydrophilic aerogels through physical adsorption. The obtained drug
      aerogel formulations were characterized by IR- and UV-spectroscopy, X-ray
      diffraction and scanning electron microscopy. Release kinetics of both drugs were
      studied in vitro. The release rate of ketoprofen from the drug-aerogel
      formulation is much faster than that of the corresponding crystalline drugs. The
      release rate of ketoprofen increases in 500% and that of griseofulvin in 450%,
      respectively. The reasons for the release enhancement are the enlarged specific
      surface area of drugs by adsorption on aerogels compared to their crystalline
      form and the immediate collapse of aerogel network in aqueous media. The
      dissolution rate of poorly water soluble drugs can be significantly enhanced by
      adsorption on highly porous hydrophilic silica aerogels.

PMID- 15581081
TI  - Dissolution of anecortave acetate in a cylindrical flow cell: re-evaluation of
      convective diffusion/drug dissolution for sparingly soluble drugs.
AB  - Steady-state drug release rates were measured from a model cylindrical implant,
      comprised mainly of the sparingly soluble drug anecortave acetate, suspended as
      an obstacle in a cylindrical flow cell. Dissolution medium was delivered at a
      steady, slow flow rate (0.05-0.7 mLs/min) using an HPLC pump, and samples from
      the outflow were analyzed by direct injection onto an HPLC column. Release rates
      were determined as a function of flow rate for three different implant
      orientations--vertical, elevated to the center of the dissolution cell;
      horizontal, elevated; and horizontal, resting directly upon the flat porous inlet
      frit. Release rates were ranked as follows: horizontal, floor >> horizontal,
      elevated>vertical, elevated. The steady, laminar flow enabled use of the finite
      element method (FEM) to simulate the dissolution process using convective
      diffusion/drug dissolution theory. Simulations predicted the absolute magnitude
      of the release rate to within < 10% for all situations, and predicted the power
      law exponent of the dependence of release rate on flow rate with great accuracy.
      The current method is more general than compendial methods that provide a
      dissolving surface that is uniformly accessible to the dissolution medium, or a
      shear rate that is uniform across the entire dissolving surface. The current
      approach may be utilized to provide estimates of dissolution rates for any
      geometry and set of hydrodynamic conditions that can be numerically calculated.

PMID- 15581082
TI  - [Immunologic criteria of health changes caused by chemicals polluting environment
      in infants and pregnant women].
AB  - The authors revealed relations-hip between pregnancy disorders and changed
      humoral immunity parameters including production of anti-hapten antibodies to
      chemical pollutants (formaldehyde, nickel and lead). The authors disclosed
      reliable correlations between immune disorders in pregnancy and specific diseases
      in newborns and infants.

PMID- 15581083
TI  - [Influence of neuroendocrine complexes on metabolic processes under exposure to
      emotional stress factors].
AB  - One of the mechanisms underlying cardiac disease caused by stress is disorder of
      lipid metabolism, resulting from excessive increase of adaptive lipotropic effect
      of stress reaction.

PMID- 15581084
TI  - [Sensomotory performance with arbitrary and fixed rhythm of hand movements].
AB  - Experimental study covered females of three age groups and revealed variation
      differences in time of arbitrary rhythmichand movements (tapping-test) and of
      movents with fixed rhythm of response to light. Their difference is represented
      as additional time for associations between cortical centers in regulation of
      hand movements.

PMID- 15581085
TI  - [Occupational medicine in Azerbaijan].
AB  - The authors demonstrate contemporary state of occupational medicine in
      Azerbaigan, define primary tasks to improve medical and prophylactic help for
      workers.

PMID- 15581086
TI  - [Ageing rate in workers of mechanic workshops of machinery construction industry
      in Armenia].
AB  - Studies of biologic age formation and ageing rate in workers of mechanic
      workshops revealed that able-bodied population grew old demographically. That is
      proved by absent age group of 20-29 years and increased share of able-bodied
      workers older than 50. Young workers aged 30-39 appeared the most vulnerable for
      occupational hazards--they demonstrated increased ageing rate and maximal excess
      of biologic age over chronological age and due biologic age.

PMID- 15581087
TI  - [Ecologic threat to human health due to increased electromagnetic background of
      environment in magnetic anomaly region (review of literature)].

PMID- 15581088
TI  - [Functional disorders of vision and their prophylaxis in professionals using PC].
AB  - With ophthalmologic examination of professionals using PC, the author specified
      functional disorders of vision. A syndrome diagnosed could be assigned to
      asthenopia. Complex of preventive measures could decrease frequency of asthenopic
      signs among PC operators and managing staffers.

PMID- 15581089
TI  - [Biologic doses of sun ultraviolet in various geographic regions of Ukraine].
AB  - The values of minimal erytemal doses (MED) were determinated for solar
      ultraviolet (UV) for two geographic zones of Ukraine taking in account the
      seasons of a year. It was calculated a daily energetic loud produced by solar UV
      in summer for persons in outdoor. The idea concerning seasonal alternations of
      human individual sensitivity to solar UV was established.

PMID- 15581090
TI  - [Using Kerdo index to evaluate vegetative homeostasis].
AB  - The authors analyse efficiency of various approaches to evaluation of vegetative
      balance in submariners and fishing sailors. The article covers suggestions of
      approaches to regulate parameters of vegetative balance, considerations of some
      features forming averages of studied values in sailors. The authors recommend
      evaluation of vegetative tone through description of regulatory mechanisms
      strain.

PMID- 15581091
TI  - [Psychophysiologic features of workers underwent trauma in meat industry].
AB  - The author studied causes of industrial injuries in meat industry of Saratov
      region. Findings are that frequent causes of accidents include psychophysiologic
      features of victims and work conditions resulting in fatigue.

PMID- 15581092
TI  - [Technogenic causes of male infertility and their prevention].

PMID- 15581093
TI  - [Correction of immunologic disorders in workers exposed to oil processing
      products in experiment].

PMID- 15581094
TI  - [Forming health in physical training workers].

PMID- 15581095
TI  - [Ectoparasites are not a rarity in Germany, too. Lice and scabies alert!].

PMID- 15581096
TI  - [Endocannabinoids receptor blocker lets tumble not only money. A drug against
      metabolic syndrome?].

PMID- 15581097
TI  - [After ambulatory arthroscopy. Pulmonary embolism notwithstanding heparin
      prophylaxis].

PMID- 15581098
TI  - [Myocardial infarct: sex-specific differences in symptoms and risk factors. In
      women sugar weighs heavier].

PMID- 15581099
TI  - [The number of new infections increases. Does syphilis come back to us?].

PMID- 15581100
TI  - [Physicians' boards want to reciprocally acknowledge continuing education points.
      Great costs for partly frightening results].

PMID- 15581101
TI  - [Floating point value. It is high time for currency reform!].

PMID- 15581102
TI  - [Whether pyromaniac, kleptomaniac, pathological gambler or messy--the impulse is
      out of control].

PMID- 15581103
TI  - [Messy house syndrome].
AB  - The messy house syndrome (Diogenes syndrome) is present when, owing to a
      disordering of the personality structure, a person is unable to keep order, for
      example, in the household or his finances. Such persons are also referred to as
      "messies". Useless objects are hoarded in such quantities that the apartment can
      no longer be lived in. In many cases, the disorder is due to an underlying mental
      problem such as dementia, schizophrenia, ADHS or obsessive-compulsive disorders.
      The Prader-Willi syndrome is also associated with an unusual compulsion to hoard
      things or food. In the first instance, treatment is aimed at the underlying
      condition (neuroleptic agents, SSRI). New studies appear to suggest that the
      particular concomitant cognitive and emotional disturbances associated with
      hoarding respond to cognitive behavioral therapy.

PMID- 15581104
TI  - [Trichotillomania: clinical presentation, causes, treatment options].
AB  - Trichotillomania (compulsive pulling out of hair) is a disorder belonging in the
      group of obsessive-compulsive disorders, the frequency of which is
      underestimated. It is a complex clinical condition comprising both compulsive and
      impulsive elements, which makes it anything but easy to treat. Currently, the
      best documented treatment options are behavioral therapy and pharmacotherapy with
      selective serotonin reuptake inhibitors.

PMID- 15581105
TI  - [Onchocerciasis].
AB  - Onchocerciasis, which is caused by filarial nematodes, affects roughly 18 million
      people in tropical Africa and is a major cause of morbidity, with a serious
      sociomedical impact. Although the present onchocerciasis control strategy
      comprising antifilarial chemotherapy and vector control is successful, it is
      associated with logistic problems due to the prolonged treatment duration.
      Furthermore, fears of drug resistance are on the increase. New approaches
      involving the use of antibiotics aimed at endobacteria living in symbiosis with
      filariae appear promising. Recent trials with tetracycline indicate a significant
      impact on worm viability.

PMID- 15581106
TI  - [Acute and chronic injuries to the knee in the doctor's office].
AB  - In the diagnostic work-up of acute and chronic injuries to the knee, the
      patient's history together with the clinical findings are of decisive importance.
      Injuries to the cruciate and lateral ligaments, or to the menisci, as well as
      osteochondritis dissecans or chronic recurrent dislocation of the patella can
      usually be reliably diagnosed on the basis of information provided by the
      patient, and diagnostic manipulations. In this connection, Lachman's test,
      various drawer phenomena, the pivot shift test, and tests of the internal menisci
      described by McMurray, Payr, Steinmann, and Cabot as well as Apley's grinding
      test have all been described. The Wilson test can indicate osteochondritis
      dissicans; in chronic recurrent dislocation of the patella, Fairbank's
      apprehension test is positive.

PMID- 15581107
TI  - [Stubborn hypertension--how to break down therapy resistance].

PMID- 15581108
TI  - [New knowledge about the effectiveness of acupuncture. Soon not to be accountable
      privately anymore?].

PMID- 15581110
TI  - [Always more specific care centers. Insurance steals private patients from family
      physicians].

PMID- 15581111
TI  - [Paradigm change in reflux disease. In reflux patients listening to is often more
      important than endoscopy].

PMID- 15581112
TI  - [Attention! Cough, asthma and Co. are often caused by reflux].

PMID- 15581113
TI  - [The 10-minute consultation. With weak discharge often past the target...].

PMID- 15581114
TI  - [Look diagnosis. Until the collar burst... ].

PMID- 15581115
TI  - Estimation and interpretation of 1/falpha noise in human cognition.
AB  - Recent analyses of serial correlations in cognitive tasks have provided
      preliminary evidence of the presence of a particular form of long-range serial
      dependence known as 1/f noise. It has been argued that long-range dependence has
      been largely ignored in mainstream cognitive psychology even though it accounts
      for a substantial proportion of variability in behavior (see, e.g., Gilden, 1997,
      2001). In this article, we discuss the defining characteristics of long-range
      dependence and argue that claims about its presence need to be evaluated by
      testing against the alternative hypothesis of short-range dependence. For the
      data from three experiments, we accomplish such tests with autoregressive
      fractionally integrated moving-average time series modeling. We find that long
      range serial dependence in these experiments can be explained by any of several
      mechanisms, including mixtures of a small number of short-range processes.

PMID- 15581116
TI  - In defense of the signal detection interpretation of remember/know judgments.
AB  - Donaldson (1996) argued that remember/know judgments can be conceptualized within
      a signal detection framework by assuming that they are based on two criteria
      situated along a strength-of-memory decision axis. According to this model, items
      that exceed a high criterion receive a remember response, whereas items that only
      exceed a lower criterion receive a know response. Although a variety of findings
      have been presented in evidence against this idea, Dunn (2004) recently showed
      that detection theory is fully compatible with those findings. We present a
      variety of new results and new analyses that weigh strongly in favor of the
      detection interpretation. We further show that a dual-process account of
      recognition memory is compatible with a unidimensional detection model despite
      the common notion that such a model necessarily assumes a single process. The key
      assumption of this model is that individual recognition decisions are based on
      both recollection and familiarity (not on one process or the other).

PMID- 15581117
TI  - Reconsidering evidence for the suppression model of the octave illusion.
AB  - The octave illusion is elicited by a sequence of tones presented to each ear that
      continuously alternate in frequency by one octave, but with high and low
      frequencies always in different ears. The percept for most listeners is a high
      pitch in one ear, alternating with a low pitch in the other ear. The influential
      suppression model of the illusion proposed by Deutsch and Roll (1976) carries
      three postulates: first, that listeners perceive only the pitch of the tones
      presented to their dominant ear; second, that this pitch is heard in whichever
      ear received the higher frequency tone; and third, that this apparent
      dissociation between what and where mechanisms arises from sequential
      interactions between the tones. In the present article, we reappraise evidence
      for the suppression model and demonstrate (1) the incompatibility of the theory
      with the existing literature on pitch perception, sound localization, and ear
      dominance and (2) methodological limitations in studies that have claimed to
      provide support for the suppression model. We conclude by proposing an
      alternative theory of the octave illusion that is based on established principles
      of fusion, rather than suppression, between ears.

PMID- 15581118
TI  - Categorization influences illusory conjunctions.
AB  - Illusory conjunctions (ICs) provide evidence for a binding problem that must be
      resolved in vision. Objects that are perceptually grouped are more likely to have
      their features erroneously conjoined. We examined whether semantic grouping,
      determined by category membership (letter vs. number), also influences illusory
      conjunction rates. Participants were instructed to detect an "L" or a "7" among
      briefly presented character strings and to report its color. Despite high shape
      discrimination accuracy, participants often made color conjunction errors,
      reporting instead the color of a distractor character, "O". This distractor could
      be ambiguously interpreted as a letter or a number. The status of the "O" was
      determined by other noncolored flanker characters, which were either letters or
      numbers. When both the target and flankers were of the same category,
      participants made more ICs than when the target and flankers were of different
      categories. This finding demonstrates that alphanumeric categorization can
      precede and subsequently influence binding.

PMID- 15581119
TI  - Perceptual grouping and attention: not all groupings are equal.
AB  - We examined grouping under inattention using Driver, Davis, Russell, Turatto, &
      Freeman's (2001) method. On each trial, two successive displays were briefly
      presented, each comprising a central target square surrounded by elements. The
      task was to judge whether the two targets were the same or different. The
      organization of the background elements stayed the same or changed, independently
      of the targets. In different conditions, background elements grouped into
      columns/rows by color similarity, a shape (a triangle/arrow, a square/cross, or a
      vertical/horizontal line) by color similarity, and a shape with no other elements
      in the background. We measured the influence of the background on the target same
      different judgments. The results imply that background elements grouped into
      columns/rows by color similarity and into a shape when no segregation from other
      elements was involved and the shape was relatively "good." In contrast, no
      background grouping was observed when resolving figure-ground relations for
      segregated units was required, as in grouping into a shape by color similarity.
      These results suggest that grouping is a multiplicity of processes that vary in
      their attentional demands. Regardless of attentional demands, the products of
      grouping are not available to awareness without attention.

PMID- 15581120
TI  - Attentional set interacts with perceptual load in visual search.
AB  - In the present study, we examined the hypothesis that perceptual load is the
      primary factor that determines the efficiency of attentional selection.
      Participants performed a visual search task under conditions of high- and low
      load. In line with the perceptual load hypothesis, presenting conditions of high-
      and low-load in separate blocks of trials resulted in processing of to-be-ignored
      stimuli only in the low-load condition (Experiment 1). However when high- and low
      load conditions were randomly mixed in blocks of trials, the participants showed
      processing of to-be-ignored stimuli in both conditions, suggesting that high
      perceptual load is not necessarily sufficient to obtain perceptual selectivity
      (Experiment 2). An analysis of intertrial transition effects showed that on high
      load trials, processing of to-be-ignored stimuli occurred only when the previous
      trial was a low-load trial. The results suggest that low perceptual load can
      engender broad attentional processing. On the other hand, when a high-load trial
      was preceded by another high-load trial, little processing of task-irrelevant
      stimuli was observed. The present results are discussed in terms of the
      interaction between expectancies and bottom-up factors in the efficiency of
      attentional selection.

PMID- 15581121
TI  - Spatial S-R compatibility effects in an intentional imitation task.
AB  - The active intermodal mapping hypothesis suggests that intentional imitation is
      mediated by a highly efficient, special-purpose mechanism of actor-centered
      movement encoding. In the present study, using methods from stimulus-response (S
      R) compatibility research, we found no evidence to support this hypothesis. In
      two experiments, the performance of adult participants instructed to imitate
      actor-centered spatial properties of head, arm, and leg movements was affected by
      task-irrelevant, egocentric spatial cues. In Experiment 1, participants imitated
      using the same side of their bodies as did the model, and performance was less
      accurate when egocentric stimulus location was response incompatible than when it
      was response compatible. This effect was reversed in Experiment 2 when
      participants imitated using the opposite side of their bodies. These findings, in
      line with general process theories of imitation, imply that intentional imitation
      is mediated by the same processes that mediate responding to inanimate stimuli on
      the basis of arbitrary S-R mappings.

PMID- 15581122
TI  - Differences between Chinese morphosyllabic and German alphabetic readers in the
      Stroop interference effect.
AB  - The goal of our study was to localize the source of the stronger Stroop
      interference effect found in morphosyllabic readers as compared with alphabetic
      readers. Twenty-three Chinese and 24 German undergraduate students were tested in
      a Stroop paradigm with the following stimuli: color patches, color-neutral words
      (e.g.,friend printed in yellow), incongruent color-associated words (e.g., blood
      printed in blue), and incongruent color words (e.g., yellow printed in blue).
      Results revealed no differences in German and Chinese students' response times to
      color patches. Chinese participants, however, showed longer color naming
      latencies for neutral words as well as for color words and color-related words.
      No differences between German and Chinese participants were found when print
      color latencies for neutral words were subtracted from print color latencies for
      color words and color-related words. This result does not support theories which
      suggest that for morphosyllabic readers there is a direct route from orthography
      to the semantics of a word. We rather argue, with reference to dual route models
      of reading, that access from print to phonology is faster for morphosyllabic than
      for alphabetic readers, and therefore interference caused by conflicting
      phonologies of color name and written word will be stronger in Chinese readers
      than in German readers.

PMID- 15581123
TI  - Episodic memory reflected in printed word naming.
AB  - Although memory is typically measured by recall or recognition, it is also
      expressed by fluent or stylized task performance. In this experiment, 12
      volunteers (called speakers) completed four experimental stages over a 2-week
      period. They read printed words aloud in two sessions, before and after exposure
      to auditory training tokens. They later completed a recognition memory test,
      discriminating old from new words. Groups of perceptual judges assessed the
      speakers' vocal imitation by comparing utterances recorded before and after
      training and deciding which sounded like "better imitations" of the training
      tokens. The data showed clear evidence of postexposure imitation, with systematic
      effects that preclude strategic explanations. The contents of episodic memory
      were reflected by participants' speaking style while they were reading aloud.
      Together, the imitation and recognition data suggest that memory preserves
      detailed traces of spoken words; those traces were apparently activated when
      participants later read the same words in the same context.

PMID- 15581124
TI  - Paws + cause = pause? Memory load and memory blends in homophone recognition.
AB  - Previous research has shown that separate information sources, activated closely
      together in time, can induce errors suggestive of memory blends. In Experiment 1,
      homophones were used to induce such memory errors. In a study task, participants
      made relatedness judgments to word pairs that included homophones (e.g., PAWS
      BEAR). During this task, one group (study-similar) maintained memory loads with
      words that were orthographically similar to the presented homophones (e.g.,
      JAWS). Another group (test-similar) maintained memory loads similar to those
      obtained for the study homophone's alternate spelling (e.g., CAUSE). A third
      group maintained no memory load during the task. In a surprise recognition test,
      participants were presented both previously viewed homophones (PAWS) and non
      presented alternate spellings (PAUSE). We hypothesized that partially activated
      alternate spellings, in conjunction with the orthographically similar memory
      words, would result in the creation of blended memories. The results followed
      suit: The test-similar condition produced significantly elevated false alarms,
      relative to both the study-similar and the no-load conditions. Experiment 2
      replicated these results while including memory loads to control for potential
      orthographic confusions. The findings are discussed in terms of multiple,
      episodic memories later activated as single, blended memories.

PMID- 15581125
TI  - Differential fan effect and attentional focus.
AB  - As people study more facts about a concept, it takes longer to retrieve a
      particular fact about that concept. This fan effect (Anderson, 1974) has been
      attributed to competition among associations to a concept. Alternatively, the
      mental-model theory (Radvansky & Zacks, 1991) suggests that the fan effect
      disappears when the related concepts are organized into a single mental model. In
      the present study, attentional focus was manipulated to affect the mental model
      to be constructed. One group of participants focused on the person dimension of
      person-location pairs, whereas the other group focused on the location dimension.
      The result showed that the fan effect with the focused dimension was greater than
      the fan effect with the nonfocused dimension, which is contrary to the mental
      model theory. The number of associations with a concept is indeed crucial during
      retrieval, and the importance of the information seems to be accentuated with
      attentional focus.

PMID- 15581126
TI  - Identification of own-race and other-race faces: implications for the
      representation of race in face space.
AB  - Own-race faces are recognized more easily than faces of a different, unfamiliar
      race. According to the multidimensional space (MDS) framework, the poor
      discriminability of other-race faces is due to their being more densely clustered
      in face space than own-race faces. Multidimensional scaling analyses of
      similarity ratings (Caucasian participants, n = 22) showed that other-race
      (Chinese) faces are more densely clustered in face space. We applied a formal
      model to test whether the spatial location of face stimuli could account for
      identification accuracy of another group of Caucasian participants (n = 30). As
      expected, own-race (Caucasian) faces were identified more accurately (higher hit
      rate, lower false alarms, and higher A') than other-race faces, which were more
      densely clustered than own-race faces. A quantitative model successfully
      predicted identification performance from the spatial locations of the stimuli.
      The results are discussed in relation to the standard MDS account of race effects
      and also an alternative "race-feature" hypothesis.

PMID- 15581127
TI  - Cognitive modeling analysis of decision-making processes in cocaine abusers.
AB  - This article examines the theoretical basis of decision-making deficits exhibited
      by cocaine abusers in a laboratory decision-making task first described by
      Bechara, Damasio, Damasio, and Anderson (1994). A total of 12 male cocaine
      abusers and 14 comparison subjects performed the task, and the cocaine group
      performed significantly worse than the comparison group. A cognitive modeling
      analysis (Busemeyer & Stout, 2002) was used to estimate three parameters that
      measure importance of the cognitive, motivational, and response processes for
      determining the observed performance deficit. The results of this analysis
      indicated, for the first time, that motivational and choice consistency factors,
      but not learning/memory were mainly responsible for the decision-making deficit
      of the cocaine abusers in this task.

PMID- 15581128
TI  - The role of guessing and boundaries on date estimation biases.
AB  - This study investigates the causes of event-dating biases. Two hundred
      participants provided knowledge ratings and date estimates for 64 news events.
      Four independent groups dated the same events under different boundary
      constraints. Analysis across all responses showed that forward telescoping
      decreased with boundary age, concurring with the boundary-effects model. With
      guesses removed from the data set, backward telescoping was greatly reduced, but
      forward telescoping was unaffected by boundaries. This dissociation indicates
      that multiple factors (e.g., guessing and reconstructive strategies) are
      responsible for different dating biases and argue against a boundary explanation
      of forward telescoping.

PMID- 15581129
TI  - Analysis of group differences in processing speed: where are the models of
      processing?
AB  - Recently, Myerson, Adams, Hale, and Jenkins (2003) replied to arguments advanced
      by Ratcliff, Spieler, and McKoon (2000) about interpretations of Brinley
      functions. Myerson et al. (2003) focused on methodological and terminological
      issues, arguing that (1) Brinley functions are not quantile-quantile (QQ) plots
      of distributions of mean reaction times (RTs) across conditions; that the fact
      that the slope of a Brinley function is the ratio of the standard deviations of
      the two distributions of means has no implications for the use of slope as a
      measure of processing speed; that the ratio of slopes of RT functions for older
      and young subjects plotted against independent variables equals the Brinley
      function slope; and that speed-accuracy criterion effects do not account for
      slowing with age. We reply by showing that Brinley functions are plots of
      quantiles against quantiles; that the slope is best estimated by the ratio of
      standard deviations because there is variability in the distributions of mean RTs
      for both older and young subjects; that the interpretation of equality of the
      slopes Brinley functions and plots of RTs against independent variables in terms
      of processing speed is model dependent; and that speed-accuracy effects in some,
      but not all, experiments are solely responsible for Brinley slopes greater than
      1. We conclude by reiterating the point that was not addressed in Myerson et al.
      (2003), that the goal of research should be model-based accounts of processing
      that deal with correct and error RT distributions and accuracy.

PMID- 15581130
TI  - Second-hand smoke exposure--who's at risk?
AB  - OBJECTIVES: This article examines exposure to second-hand smoke (SHS) in 2003 in
      various settings by age and sex, and compares exposure indicators by province and
      health region. DATA SOURCE: The data are from the 2000/01 and 2003 Canadian
      Community Health Survey, conducted by Statistics Canada. ANALYTICAL TECHNIQUES:
      Rates of exposure to SHS among non-smokers are calculated by sex, age and
      location for the household population aged 12 or older. Rates of exposure at work
      are examined for employed non-smokers aged 15 or older. Smoking prevalence is
      expressed as a percentage of the household population aged 12 or older. MAIN
      RESULTS: In 2003, 33% of non-smokers reported that they were regularly exposed to
      SHS. The risk of exposure was greatest in public spaces, but regardless of
      setting, rates of exposure were higher for men than women. Exposure rates varied
      by age and peaked in young adulthood. However, at home and at work, the younger
      the non-smokers, the more likely they were to be exposed to SHS. Disparities in
      SHS exposure by province/territory and by health region were substantial.

PMID- 15581131
TI  - Shorter hospital stays for breast cancer.
AB  - OBJECTIVES: This article examines trends in and factors influencing the length of
      stay for female breast cancer patients who were hospitalized between 1981 and
      2000. DATA SOURCES: The hospital data are from the Hospital Morbidity Database
      and the Health Person-oriented Information Database, both maintained by
      Statistics Canada. Data on new cases of breast cancer are from the Canadian
      Cancer Registry and the National Cancer Incidence Reporting System. ANALYTICAL
      TECHNIQUES: Descriptive analyses present length of stayfor all hospital
      admissions with a primary diagnosis of breast cancer, by four-year period and by
      the patient's age, cancer stage, comorbid conditions and surgical procedures.
      Logistic regression is used to examine associations between these factors and
      length of stay. MAIN RESULTS: Since the early 1980s, the average length of stay
      in hospital for female breast cancer has fallen from 15.1 to 4.5 days. Declines
      occurred regardless of age group, cancer stage, procedure and comorbid
      conditions. Average stays first began to fall for less serious cases, but were
      eventually apparent for even the most serious.

PMID- 15581132
TI  - Use of hospital emergency rooms.

PMID- 15581133
TI  - Dental consultations.

PMID- 15581134
TI  - Vision problems among seniors.

PMID- 15581135
TI  - Mental health services in the courts: a program review.

PMID- 15581136
TI  - BC 2003 wildland urban interface fires: managing an integrated health system
      during a regional emergency.

PMID- 15581137
TI  - Case against Northern Ireland vet dismissed.

PMID- 15581138
TI  - Nurses or mini-vets? A struggle for identity.

PMID- 15581139
TI  - New cattle health planning standards.

PMID- 15581140
TI  - Clinical findings in 78 suspected cases of bovine spongiform encephalopathy in
      Great Britain.
AB  - The clinical findings in 59 cows with bovine spongiform encephalopathy (BSE) were
      compared with those in 19 cattle that were submitted as BSE suspects but not
      confirmed by immunohistochemistry. Both groups were also compared with a control
      group of 20 healthy cows. Abnormalities in behaviour, temperament, mental status
      and activity, neurogenic disorders of gait and hyperreactivity to touch were
      frequently observed in the cattle with BSE. Not every animal with BSE displayed
      clinical signs in all these categories, and the severity of the signs was not
      always useful for differentiating them from the BSE suspects that were not
      confirmed by pathology. The neurological examination was better than passive
      observations for the clinical diagnosis of BSE. Tests of the animals' responses
      to sudden auditory, visual and tactile stimuli were very useful for
      distinguishing cases of BSE from unconfirmed BSE suspects if the cases did not
      display signs in all the categories.

PMID- 15581141
TI  - Comparison of the analgesic effects of meloxicam and carprofen administered
      preoperatively to dogs undergoing orthopaedic surgery.
AB  - Thirty-two dogs undergoing operations to repair a torn cranial cruciate ligament
      or a fractured long bone were randomly allocated to one of two treatment groups
      in a study on postoperative pain. Sixteen of the dogs were given 4 mg/kg
      carprofen and the other 16 were given 0.2 mg/kg meloxicam subcutaneously before
      the operation. The signs of pain shown by the animals were assessed for 24 hours
      on a visual analogue scale, a discontinuous scoring system, and a score based on
      five behavioural and physiological variables. The dogs' heart and respiratory
      rates and their mean arterial blood pressures were also measured non-invasively
      at each assessment. Blood samples were taken before the surgery and 24 hours
      after it, and the concentrations of urea and creatinine were measured in plasma.
      Both drugs were effective in relieving the signs of pain for up to 24 hours in
      all the dogs. There were no significant changes in the concentrations of urea and
      creatinine, and no adverse effects were reported during the postoperative period.

PMID- 15581142
TI  - Serum activity/concentration profiles of a sustained-released formulation of
      sulphathiazole-trimethoprim (2.5:1) in calves.
AB  - Thirty-six two-week-old healthy Holstein-Friesian calves weighing between 52 and
      58 kg were divided at random into three groups of 12; group A calves were given a
      single oral bolus containing 2.5 g sulphathiazole and 1 g trimethoprim in a
      sustained-release formulation; group B received the same doses of the drugs but
      the trimethoprim was not in a sustained-release formulation; group C received a
      bolus containing 2.5 g sulphathiazole and 0.5 g conventional trimethoprim. Blood
      samples were collected at intervals for two days, the serum was separated and the
      composite antibacterial activity profiles of the mixture were analysed by an agar
      diffusion microbiological method. The mean maximum activities in the serum of the
      three groups were 23.4 microg/ml in group A, 9.25 microg/ml in group B and 8.01
      microg/ml in group C. The mean areas under the curves of the serum activity time
      curves were 838 microg/ml/hour in group A, 216 microg/ml/hour in group B and 182
      microg/ml/hour in group C.

PMID- 15581143
TI  - Hypomagnesaemic tetany in lactating Cheviot gimmers associated with pasture
      sodium deficiency.

PMID- 15581144
TI  - Osteochondrosis associated with copper deficiency in a red deer herd in Norway.

PMID- 15581145
TI  - Clinical and pathological features of a cardiac chondrosarcoma in a dog.

PMID- 15581146
TI  - Occurrence of vancomycin-resistant enterococci in ducks in Malaysia.

PMID- 15581147
TI  - Change to milk withdrawal period for LEO Yellow Milking Cow.

PMID- 15581148
TI  - Standards for international trade.

PMID- 15581149
TI  - Effect of trace element supplementation on the fertility of dairy herds.

PMID- 15581150
TI  - Enjoyable meals.

PMID- 15581151
TI  - Impact of gastrostomy tube feeding on the quality of life of carers of children
      with cerebral palsy.
AB  - The aim of this prospective cohort study was to evaluate the impact of
      gastrostomy tube feeding on the quality of life of carers of children with
      cerebral palsy (CP). Short-Form 36 version II was used to measure quality of life
      in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y
      4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy
      tube. Responses were calibrated against a normative dataset (Oxford Healthy Life
      Survey III). Six months after gastrostomy feeding was started, a substantial rise
      in mean domain scores for mental health, role limitations due to emotional
      problems, physical functioning, social functioning, and energy/vitality were
      observed. At 12 months after gastrostomy placement, carers reported significant
      improvements in social functioning, mental health, energy/vitality (mean increase
      >9.8 points;p<0.03), and in general health perception (mean increase 6.35
      points;p=0.045) compared with results at baseline. Moreover, the values obtained
      for these domains at 12 months were not significantly different from the normal
      reference standard. Carers reported a significant reduction in feeding times,
      increased ease of drug administration, and reduced concern about their child's
      nutritional status. This study has demonstrated a significant, measurable
      improvement in the quality of life of carers after insertion of a gastrostomy
      feeding tube.

PMID- 15581152
TI  - Drooling, saliva production, and swallowing in cerebral palsy.
AB  - Fourteen participants (six females, eight males) ranging in age from 7 years 11
      months to 18 years 2 months (mean 11y 7mo) with a confirmed diagnosis of spastic
      cerebral palsy (CP) were included in the study. Participants included those who
      drooled (CP+, n=14); age- and sex-matched children with spastic CP who were dry
      to mild and never to infrequent droolers (CP-, n=14) as well as typically
      developing peers (CTRL, n=14) served as controls. Frequency of swallowing was
      measured by using simultaneous cervical ausculation and videotaping of the head
      and neck. Saliva production was measured with the Saxon test, a simple gauze
      chewing procedure. In addition, Pediatric Evaluation of Disability Inventory
      (PEDI), Test of Nonverbal Intelligence-3 (TONI-3), dysarthria severity scale, and
      Gross Motor Function Classification System (GMFCS) scores were obtained for each
      participant. Both groups of participants with CP tended to swallow less
      frequently than typically developing participants and tended to produce less
      saliva than typically developing controls; however, these differences were not
      statistically significant. No correlation was found between amount of saliva
      produced and amount drooled (r=0.245). An analysis of variance (ANOVA) conducted
      on the PEDI functional skills mean scores indicated significant differences
      between the three groups (F(2,39)=23.522,p<0.0001). Likewise, an ANOVA conducted
      on the TONI-3 scores revealed statistically significant differences between the
      three groups (F(2,39)=31.761, p<0.0001). A Spearman's rho correlation indicated
      that GMFCS scores were not significantly correlated with drooling severity
      (Spearman's rho correlation=0.3951,p=0.037). Drooling severity was found to be
      positively correlated with dysarthria severity (Spearman's rho
      correlation=0.82,p<0.0001). These findings suggest that drooling in patients with
      CP is related to swallowing difficulties rather than hypersalivation.

PMID- 15581153
TI  - Efficacy of botulinum toxin A, serial casting, and combined treatment for spastic
      equinus: a retrospective analysis.
AB  - Botulinum toxin type A (BTX-A), serial casting, and combined treatment for
      spastic equinus were compared by chart review. Fifty-five patients with diplegia
      (n=21), hemiplegia (n=17), quadriplegia (n=6), and other diagnoses (n=11) were
      reviewed. Thirty-one patients had Gross Motor Function Classification System
      (GMFCS) scores of I or II, 10 had a GMFCS score of III, and eight had GMFCS
      scores of IV or V (for six there were no available data). Mean age was 7 years 1
      month (SD 4 y 8mo). The combined group showed a significantly greater increase in
      passive range of motion (ROM) of the ankle joint in comparison with BTX-A alone
      (p=0.0002), with a mean of 17 degrees (SD 11.2) versus 5 degrees (SD 6.7), and
      casting alone showed a significantly greater increase in comparison with BTX-A
      alone (p=0.0001), with a mean of 15 degrees (SD 4.5) versus 5 degrees (SD 6.7).
      With cast number controlled, change in ROM after casting with and without BTX-A
      was not significantly different (p=0.37). There was no significant difference
      between casting with or without BTX-A, and both improved ROM to a greater degree
      than BTX-A alone. Casting demonstrated a significantly more robust impact on
      range of motion than BTX-A alone.

PMID- 15581154
TI  - Is improved survival of very-low-birthweight infants in the 1980s and 1990s
      associated with increasing intellectual deficit in surviving children?
AB  - To investigate whether the decrease in mean birthweight of the smallest infants
      surviving with a very low birthweight (VLBW) in the past two decades is
      associated with an increase in intellectual deficit rates, we compared the
      results obtained in two different follow-up studies: one included a cohort of
      children of VLBW (<1500g; n=102, 52% male) born in the early 1980s; the other
      included a cohort of children of extremely low birthweight (ELBW; <1000g; n=183,
      46% male) born in the mid-1990s. Intellectual development was evaluated in both
      cohorts. McCarthy Scales of Children's Abilities were used in the cohort from the
      early 1980s; Wechsler's Preschool and Primary Scale of Intelligence--Revised was
      used in the cohort from the mid-1990s. The children were assessed at age 4-5
      years, and a control group was included for each of the two studies. Mean scores
      in the measures of intelligence found at the assessment were recalculated to
      standard deviation scores from the two control groups. We found no difference in
      the standard deviation scores between the two cohorts despite the mean
      birthweight being 353g (p<0.001) lower in the cohort from the mid-1990s, and the
      overall survival rate of infants of VLBW having increased. Our results suggest
      that the improved survival of the smallest babies in the 1980s and 1990s has been
      achieved without an increase in the intellectual deficit in the surviving
      children.

PMID- 15581155
TI  - Altered pathways for auditory discrimination and recognition memory in preterm
      infants.
AB  - Preterm infants are at increased risk for cognitive disorders, including
      impairments in recognition memory. This study evaluated the effects of extreme
      prematurity on the neural pathway for auditory recognition memory using event
      related potentials (ERPs), a neurophysiological technique widely used in
      cognitive neuroscience. ERPs were recorded at term postmenstrual age in 35
      preterm infants born at less than 32 weeks' gestation (22 males, 13 females; mean
      birthweight ([BW] 1154g, SD 374g) with normal brain ultrasounds, compared with 40
      healthy, term newborns (1 to 3 days of age; 20 males, 20 females; BW 3672g, SD
      420g). Because infants must be able to detect and discriminate sounds before
      recognizing them, two paradigms were used to assess these functions. The first
      evaluated the detection and discrimination of speech sounds. The second tested
      recognition of the mother's voice compared with a stranger's. Results showed
      significantly different patterns of speech sound discrimination in preterm
      infants compared with term infants. No evidence of maternal voice recognition was
      elicited from the preterm infants. No specific patterns of auditory detection or
      discrimination were associated with patterns of recognition memory, suggesting
      that the function of multiple neural pathways may have been altered in this group
      of preterm infants. These results provide a functional corroboration of magnetic
      resonance imaging studies showing effects of prematurity on early brain
      development, even among preterm infants with normal cranial ultrasonography.

PMID- 15581156
TI  - Lead exposure and attention regulation in children living in poverty.
AB  - This study examined the relationship between lead exposure and attention
      regulation in children from low-income families. Children with lead exposure were
      expected to have lower attention regulation abilities than children who were not
      exposed. The 57 participants (39% male, 61% female) were children aged 4 and 5
      years (mean age 4y 7mo [SD 5mo]); 24 children were lead-exposed (10-29microg/dl)
      and 33 were non-exposed comparisons (1-6microg/dl). Both groups qualified to be
      enrolled in programs for low-income families. A puzzle-matching task was
      completed in parent-child and child-alone conditions. Attention allocation and
      puzzle-matching performance were assessed in the two conditions. Children who
      were lead-exposed demonstrated less self-regulated attention than comparisons and
      had poorer puzzle performance in the child-alone condition. Attention patterns
      did not differ in the parent-child condition. This study extends previous
      knowledge concerning effects of lead exposure on preschool children from
      disadvantaged environments and suggests that lead exposure affects specific
      attention regulation abilities.

PMID- 15581157
TI  - Neurocognitive profiles in Salla disease.
AB  - Salla disease, a free sialic acid storage disorder, is one of the 36 currently
      known disorders in Finland that form the Finnish disease heritage. Salla disease
      leads to learning disability* with a wide clinical variation. Two main categories
      of the disease have been classified: a conventional subtype and a severe subtype
      with more severe defects. We present detailed neurocognitive profiles of 41
      Finnish patients with Salla disease (19 females, 22 males; age range 11mo to 63y,
      median 19y). The neurocognitive development of patients with Salla disease was
      assessed by psychological and neuropsychological testing. All patients were also
      examined by a paediatric neurologist and a speech therapist. The characteristic
      cognitive profile consisted of a lower non-verbal performance (mean developmental
      age 13mo) compared with linguistic skills (mean developmental age 17mo). In
      particular, spatial and visual-constructive impairments were typical of these
      patients. Tactile and visual discrimination of forms was poor. Tasks demanding
      hand-eye coordination, maintenance of visual attention, and those requiring short
      term visual memory and executive skills were performed better. Receptive language
      skills were notably better compared with expressive speech. The patients'
      interactive and non-verbal communication skills were quite strong. Another
      typical pattern with Salla disease was severe motor disability. After the second
      decade of life, the decline in these skills was more pronounced than patients'
      cognitive deterioration. Our results indicate that even though there is a
      considerable variation in the clinical findings of patients with Salla disease,
      the characteristic neurocognitive profile of the disease can be outlined.

PMID- 15581158
TI  - Clinical course of spontaneous spinal epidural haematoma mimicking Guillain-Barre
      syndrome in a child: a case report and literature review.
AB  - We describe a 9-year-old female with thoracic epidural haematoma. The clinical
      course simulated Guillain-Barre syndrome (GBS) so intravenous immunoglobulin
      therapy was started at the paediatric clinic. Magnetic resonance imaging (MRI) 3
      days after admission showed thoracic epidural haematoma between T2 and T8. An
      emergency laminectomy was performed and the patient's neurological symptoms began
      to improve immediately after surgery and she made a full recovery during the 2
      weeks of follow-up. Time is a very important factor in achieving reversibility of
      symptoms of compressive cord lesions, such as spinal epidural haematoma, and MRI
      is mandatory for patients with progressive paraplegia, even though the signs and
      symptoms might suggest GBS.

PMID- 15581159
TI  - Cerebral folate deficiency.
AB  - Cerebral folate deficiency (CFD) can be defined as any neurological syndrome
      associated with low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF),
      the active folate metabolite, in the presence of normal folate metabolism outside
      the nervous system. CFD could result from either disturbed folate transport or
      from increased folate turnover within the central nervous system (CNS). We report
      on a novel neurometabolic syndrome in 20 children, which we term 'idiopathic
      CFD'. Typical features became manifest from the age of 4 months, starting with
      marked unrest, irritability, and sleep disturbances followed by psychomotor
      retardation, cerebellar ataxia, spastic paraplegia, and dyskinesia; epilepsy
      developed in about one third of the children. Most children showed deceleration
      ofhead growth from the age of 4 to 6 months. Visual disturbances began to develop
      around the age of 3 years and progressive sensorineural hearing loss started from
      the age of 6 years. Neuroimaging showed atrophy of frontotemporal regions and
      periventricular demyelination in seven children, slowly progressive supra- and
      infratentorial atrophy in three children, and normal findings in the remainder.
      Because active folate transport to the CNS occurs through receptor-mediated
      folate receptor protein 1 (FR1) endocytosis, DNA sequencing of the FR1 gene was
      performed and found to be normal. However, CSF protein analysis revealed a non
      functional FR1 protein, suspected to result from either post-translational
      defects of FR1 protein N-glycosylation, the presence of folate antagonists with
      irreversible binding, or autoantibodies blocking the folate binding site of FR1.
      Oral treatment with 5-formyltetrahydrofolate (folinic acid) should be started in
      low doses at 0.5-1mg/kg/day, but in some patients higher daily doses of folinic
      acid at 2-3 mg/kg/day are required to normalize CSF 5MTHF values. This proposed
      treatment protocol resulted in a favourable clinical response in patients
      identified before the age of six years while partial recovery with poorer outcome
      was found beyond the age of 6 years. Careful clinical and EEG monitoring should
      be performed 1, 3, and 6 months after the beginning of treatment. After four to
      six months of folinic acid treatment, CSF analysis should be repeated in order to
      prevent over- or under-dosage of folinic acid. Secondary forms of CFD have been
      recognized during chronic use of antifolate and anticonvulsant drugs and in
      various known conditions such as Rett syndrome, Aicardi-Goutieres syndrome, 3
      phosphoglycerate dehydrogenase deficiency, dihydropteridine reductase deficiency,
      aromatic amino acid decarboxylase deficiency, and Kearns-Sayre syndrome. The
      pathogenic link between these underlying specific disease entities and the
      observed secondary CFD has not been resolved.

PMID- 15581160
TI  - "Supramalleolar orthoses and postural stability in children with Down syndrome-
      Banta replies".

PMID- 15581161
TI  - Morphologic characteristics of p16INK4a-positive cells in cervical cytology
      samples.
AB  - OBJECTIVE: Overexpression of p16INK4a has been proposed as a biomarker helpful
      for the identification of dysplastic cervical epithelial cells on histologic
      slides as well as in cervical smears. Since a few nontransformed cells in the
      genital tract in some instances may also express p16INK4a, we evaluated whether
      applying established morphologic criteria for cervical dysplasia allows a
      distinction of dysplastic from nondysplastic p16INK4a-stained cells in cytologic
      samples. STUDY DESIGN: Liquid-based cytology samples were obtained from a
      screening population (n=50), and from patients attending a dysplasia clinic
      (n=40). Slides prepared from these samples were stained with the conventional
      Papanicolaou stain procedure. From each specimen, a second slide was prepared in
      parallel and immunostained for p16INK4a. Cytologic diagnoses for most patients
      attending the dysplasia clinic could be compared to the reported histologic
      diagnoses on punch biopsy samples taken from the patients at the time of
      colposcopy. This allowed a comparison of the cytology and p16INK4a immunostaining
      results with subsequent hematoxylin and eosin-based histologic diagnoses.
      RESULTS: Overall, in 10% of slides obtained from patients with nonsuspicious
      smears, few p16INK4a-positive cells were found. Using established morphologic
      criteria and applying these criteria on cells showing any p16INK4a
      immunoreactivity, p16INK4a-positive normal or metaplastic cells could be
      discriminated from p16INK4a-expressing dysplastic cells. In 21 of 22 cases (95%)
      of high grade lesions (cervical intraepithelial neoplasia 2 or higher in follow
      up histology), easily recognizable p16INK4a-positive dysplastic cells could be
      detected, with the remaining case lacking dysplastic cells in the thin-layer
      slide used for p16INK4a immunostaining. CONCLUSION: Established morphologic
      criteria for cervical dysplasia can be readily applied to p16INK4a-immunostained
      cytologic specimens. Thus, p16INK4a immunostaining may help to avoid ambiguities
      in the interpretation of cervical cytology samples and facilitate more rapid
      diagnosis and possibly even automated screening of cytologic slides.

PMID- 15581162
TI  - Eliminating the diagnosis atypical squamous cells of undetermined significance:
      impact on the accuracy of the Papanicolaou test.
AB  - OBJECTIVE: To assess eliminating the diagnosis "atypical squamous cells of
      undetermined significance" (ASCUS) from the Bethesda System for Reporting
      Cervical/Vaginal Cytological Diagnoses and analyze its impact on the sensitivity
      and positive predictive value of Pap smears. STUDY DESIGN: A total of 166
      previously diagnosed ASCUS cases with follow-up biopsy results available were
      prospectively downgraded to within normal limits/benign cellular changes or
      upgraded to specific squamous intraepithelial lesions (SILs) or the malignant
      category. These review cytodiagnoses were compared with the histologic outcome.
      The impact on the sensitivity and positive predictive value of Pap smears was
      also assessed. RESULTS: Though there was a decrease in the sensitivity of the Pap
      smear from 100% to 76.3% for SIL overall and from 100% to 80% for high grade SIL
      (HSIL) alone, there was an improvement in the positive predictive value of
      diagnosing SIL from 46% to 85% and from 6% to 15% for HSIL alone. CONCLUSION: The
      ASCUS diagnosis can be minimized to a great extent, if not eliminated completely.
      The "ASCUS-favor reactive" group can be eliminated, while the diagnoses "ASCUS
      favor SIL" and "ASCUS-not otherwise specified" should be used sparingly.

PMID- 15581163
TI  - Comparison of cytology proficiency testing: glass slides vs. virtual slides.
AB  - OBJECTIVE: To compare proficiency testing in gynecologic cytology using glass
      slides vs. virtual slides. STUDY DESIGN: To compare performance, a sample of 111
      individuals (pathologists = 52, cytotechnologists = 59) from participating in
      state laboratories were administered 2 proficiency tests. The annual test of the
      Maryland Cytology Proficiency Testing Program (MCPTP) was administered to
      individuals in their laboratories following normal work practice (i.e., using
      microscopes and equipment with which they were familiar). The other test was
      CytoView II (Centers for Disease Control and Prevention, Atlanta, Georgia,
      U.S.A.), a computer-based test composed of virtual slides captured from the
      MCPTP's glass slides, which test administration personnel transported to the
      individual's laboratory and administered using 1 of 2 laptop computers. ANOVA was
      used to compare the performance on the 2 tests and the effect of various
      potential confounding variables. The slides were evaluated by comparing the
      performance average for each glass slide to that of the matching virtual slides.
      All data analysis was performed at the 95% confidence interval. RESULTS: The mean
      score of the individuals (n = 111) on the MCPTP test was 99.2% (SD = 2.2, range =
      90-100%). The mean score of the individuals (n = 111) on CytoView II was 96.8%
      (SD = 5.8, range = 70-100%). No individual scored < 90% on the glass slide test
      (pass rate = 100%). Eight individuals (pathologists = 3, cytotechnologists = 5)
      scored < 90% on the CytoView II (pass rate = 93.8%). Comparison of an
      individual's performance on the 2 tests demonstrated a significant difference.
      When virtual slides that did not attain a 90% consensus were excluded from the
      scoring, a comparison of individual pass rate for the glass slide test (100%) and
      computer-based test (99.1%) did not demonstrate significant difference.
      CONCLUSION: Each slide (glass or virtual) must be field validated by
      cytotechnologists and pathologists. If field validation and Clinical Laboratory
      Improvement Amendment referencing of virtual slides are comparable to those of
      glass slides, computer-based testing can be equivalent.

PMID- 15581164
TI  - Morphologic spectrum of papillary carcinoma of the thyroid: role of cytology in
      identifying the variants.
AB  - OBJECTIVE: To evaluate the efficacy of fine needle aspiration cytology (FNAC) in
      the diagnosis of morphologic variants of papillary carcinoma of the thyroid (PCT)
      and to determine the reasons for misdiagnosis in discrepant cases on cytology.
      STUDY DESIGN: Fine needle aspiration smears from 158 histologically proven cases
      of PCT were blindly reviewed and an attempt made to subclassify them into
      different variants on the basis of various architectural and morphologic
      features. Cytohistologic correlation was performed to assess the efficacy of
      cytology in correctly identifying these variants. RESULTS: In cases with
      satisfactory aspirates, the diagnosis of papillary carcinoma was correctly made
      in 112 of 139 (80.5%) histologically proven cases of PCT. Subclassification was
      correct in 87 of 96 (90.6%) cases of classic papillary carcinoma and in 25 of 43
      (58.1%) of the other variants of PCT with adequate aspirates. Cytohistologic
      agreement was 100% in columnar cell variant (CCV) and high grade variant (HGV).
      Although there was overlap in the morphologic features of tall cell variant (TCV)
      and Hurthle cell variant, cytology correctly identified 60% and 76.4% of these
      cases, respectively. The accuracy of cytology was limited in diagnosing
      follicular variant as only 50% of these cases could be correctly typed on
      cytology. Nodular fascitis-like stroma and diffuse sclerosis variants could not
      be diagnosed on cytology. CONCLUSION: Though FNAC is of limited value in typing
      the variants of PCT due to overlapping morphologic features, it can provide clues
      to the diagnosis in certain aggressive variants such as TCV, CCV and HGV. Early
      diagnosis in these cases can assist clinicians with management.

PMID- 15581165
TI  - Analysis of fine needle aspiration cytology of the breast: a review of 1,297
      cases and correlation with histologic diagnoses.
AB  - OBJECTIVE: To evaluate the accuracy of fine needle aspiration (FNA) cytology of
      the breast and to ascertain its usefulness. STUDY DESIGN: The authors reviewed
      1,297 cases of FNA cytology of the breast which were performed at Chonnam
      National University Hospital from 1999 to 2002. Cytologic diagnoses were compared
      with histologic diagnoses in 457 cases that underwent both cytologic and
      histologic examination. RESULTS: Of 1,297 cases, 1,201 (92.6%) were satisfactory
      and 96 (7.4%) unsatisfactory. Subsequent histologic examination was performed on
      291 cases (29.7%) out of 981 "benign" lesions, 28 (73.7%) of 38 "suspicious," 124
      (68.1%) of 182 "malignant" and 14 (14.6%) of 96 "unsatisfactory." FNA cytology
      revealed 77.7% sensitivity, 99.2% specificity, 98.4% positive predictive value
      and 88.0% negative predictive value. Diagnostic accuracy was 91.1%. Of the 291
      benign cases on cytology, 35 cases were malignancy on histology. Of the 124 cases
      reported as malignant, 2 were benign. Interpretive error was the leading cause of
      false positive diagnoses. CONCLUSION: Although FNA cytology is a useful
      diagnostic procedure for the evaluation of breast lesions, it should be combined
      with other diagnostic modalities, such as physical examination, ultrasonography
      and mammography.

PMID- 15581166
TI  - Patterns of testicular cytology in men with primary infertility: any change since
      the Gulf War?
AB  - OBJECTIVE: To evaluate the patterns of testicular cytology in men with primary
      infertility, to compare the morphologic patterns between the periods 1990-1995,
      immediately after Gulf War II, and 1997-2001 and to determine whether there is a
      correlation between hormonal profile, testicular volume and morphologic pattern.
      STUDY DESIGN: Retrospective study of men with primary infertility. History,
      complete physical examination, hormonal assay and testicular ultrasound were
      evaluated. A total of 545 patients had samples for testicular cytology obtained
      from both testes. The patient's consent was obtained in all cases. Smears were
      interpreted under light microscopy after treatment with Diff-Quik. A total of 104
      healthy, fertile subjects were used for comparison of the hormonal profile and
      testicular volume. RESULTS: The mean (+/- SD) age was 28.66 +/- 4.36 years and
      duration of marriage 4.4 +/- 4.36 years. There were 11.2% patients with normal
      cytology, 55.8% with hypospermatogenesis, 28.4% with testicular atrophy, 2.9%
      with Sertoli cells only and 1.7% with maturation arrest. A significant increase
      in hypospermatogenesis and decrease in the Sertoli cell-only pattern were noted
      in 1997-2001 when compared with 1990-1995. The mean left testicular volume was
      10.53 +/- 5.51 mL3 in the infertile group vs. 15.2 +/- 4.97 in the fertile group
      (p < 0.003); right testicular volume was 10.84 +/- 4.77 vs. 15.15 +/- 5.31 (p <
      0.003). The hormonal profile revealed higher luteinizing hormone and follicle
      stimulating hormone levels in the infertile group vs. control group (8.53 +/-
      9.03 and 16.44 +/- 19.243 vs. 6.98 +/- 4.53 and 7.37 +/- 6.63, respectively [p <
      0.001]). Free testosterone was higher in the fertile group (39.69 +/- 12.76 vs.
      20.28 +/- 8.5 [p < 0.000]). CONCLUSION: The majority of infertile males in our
      cohort had hypospermatogenesis; testicular atrophy was the next most common
      disorder. There was no major change in overall absolute numbers since the Gulf
      War. Testicular cytology by fine needle aspiration is a safe and well-tolerated
      complementary investigation for unexplained male infertility.

PMID- 15581167
TI  - Multiple sampling for increasing the diagnostic sensitivity of nipple aspirate
      fluid for atypical cytology.
AB  - OBJECTIVE: To determine if repeated collection of nipple aspirate fluid (NAF) can
      improve the diagnostic sensitivity for cytologic atypia, a marker of increased
      risk of breast cancer. STUDY DESIGN: Two hundred sixty-seven women without known
      breast disease volunteered for NAF cytology at 5 6-month intervals over 2 years.
      NAF samples were prepared on Millipore filters (Millipore Filter Corp., Bedford,
      Massachusetts, U.S.A.) and stained with a modified Papanicolaou method. Fluid
      availability and cellular abnormalities were evaluated for each collection
      attempt. Cellular findings were classified as benign, hyperplasia or atypia.
      RESULTS: NAF was obtained from 178 women (66.6%) at the first visit and from an
      additional 15, 10, 2 and 4 women at visits 2, 3, 4 and 5, respectively, for a
      cumulative total of 78.2% by visit 5. The number of women yielding NAF containing
      hyperplastic or atypical epithelial cells was determined at each visit.
      Hyperplastic cells were found in 34 (19.1%) at visit 1 and in an additional 20,
      10, 5 and 4 women at visits 2, 3, 4 and 5, respectively. Atypical epithelial
      cells were present in 12 (6.7%) women at the initial visit and in an additional
      11, 7, 5 and 1 women at visits 2, 3, 4 and 5, respectively, for a cumulative
      percent of 18.2 at visit 5. NAF could not be obtained from 58 women at any visit.
      CONCLUSION: These findings suggest that an optimum collection method for NAF
      cytology should consist of at least 3 or 4 separate fluid aspiration attempts.
      Reviewing repeated multiple samples instead of 1 increases the number of women
      who can be evaluated and the likelihood of detecting cytologic atypia.

PMID- 15581168
TI  - Telomerase activity in thyroid fine needle aspirates.
AB  - OBJECTIVE: To study the utility of telomerase activity (TA) detection in thyroid
      fine needle aspirates (FNAs). STUDY DESIGN: One hundred two thyroid nodules were
      studied: 70 in FNA samples and 32 in frozen tumors. From among FNA samples, there
      were 57 nodules of the goiter, 1 adenoma, 7 papillary carcinomas, 1 medullary
      carcinoma and 1 lymphoma. Three cases of thyroiditis were excluded. The 32 frozen
      tissue tumors consisted of 5 follicular adenomas, 4 follicular carcinomas and 23
      papillary carcinomas. TA was analyzed by Telomerase PCR ELISA (Roche Diagnostics,
      Indianapolis, Indiana, U.S.A.). RESULTS: TA was negative in the 57 nonneoplastic
      nodules and 6 follicular adenomas and positive in 3 of 4 follicular carcinomas
      and 10 of 30 papillary carcinomas. TA sensitivity was 41.4% and specificity 100%.
      Sensitivity for malignancy was higher (85.7%) in FNAs than in TA. CONCLUSION: TA
      seems highly specific for neoplasms of the thyroid. Further studies are needed to
      confirm whether TA detection could contribute to identifying neoplasms when FNAs
      are inconclusive for malignancy and in cases of scanty material.

PMID- 15581169
TI  - Use of liquid-based cytology in serous fluids: a comparison with conventional
      cytopreparatory techniques.
AB  - OBJECTIVE: To examine the performance of liquid-based cytology (LBC) on body
      cavity fluids as compared with conventional cytopreparatory techniques. STUDY
      DESIGN: Slides from a total of 592 serous fluids, effusions as well as
      intraoperative washings, were reviewed. Of these fluids, 301 were collected
      before and 291 after the introduction of the PrepStain LBC (TriPath Imaging,
      Burlington, North Carolina, U.S.A.) in our laboratory. RESULTS: PrepStain thin
      layers showed excellent morphology on a clear background, with preservation of 3
      dimensional configurations and a sufficient amount of extracellular material to
      allow an accurate diagnosis. Cytopreparation, screening and interpretation of LBC
      were less time consuming. Moreover, when the performance of the various
      cytopreparatory techniques in malignant fluids was studied, PrepStain thin layers
      excelled over conventional cytopreparatory methods in showing a significantly
      lower false negative rate (P=.0414). CONCLUSION: Our findings indicate that in
      body fluid cytology, thin layers can safely replace other types of wet-fixed
      preparations, resulting in enhanced specimen quality and diminished false
      negative rates.

PMID- 15581170
TI  - Malignant rhabdoid tumor of the kidney in a child: report of a case with
      recurrence in the contralateral kidney.
AB  - BACKGROUND: Malignant rhabdoid tumor (MRT) of the kidney is a rare and aggressive
      neoplasm with a controversial histogenesis. Although their immunohistochemistry
      may be diverse, the rhabdoid phenotype and mutations of the INI1 gene are
      consistently exhibited by MRTs regardless of their location. CASE: MRT recurred
      in the contralateral kidney in a 12-month-old child within 6 months after the
      initial histologic diagnosis, nephrectomy and autologous stem cell transplant.
      The presence of widespread metastases at the time of the recurrence precluded any
      further chemical and surgical diagnostic or therapeutic intervention. CONCLUSION:
      To the best of our knowledge, only a few cases describing the cytologic diagnosis
      of MRT of the kidney in a child have been reported. This case illustrates the
      usefulness of cytologic diagnosis in an MRT recurrence.

PMID- 15581171
TI  - Fine needle aspiration cytology of collecting duct carcinoma of the kidney:
      report of a case with distinctive features and differential diagnosis.
AB  - BACKGROUND: The relative rarity of collecting duct carcinoma (CDC) of the kidney
      in conjunction with a lack of distinctive cytologic features is a diagnostic
      challenge for any cytopathologist when dealing with such a tumor on fine needle
      aspiration cytology. In previous cytologic reports, CDC is not well
      characterized, and the features overlapped with those of high grade renal cell
      carcinoma (RCC). Because of the differences in behavior and treatment from
      conventional RCC, it is important to attempt to diagnose this tumor correctly.
      CASE: The cytologic findings of CDC in a 56-year-old woman were distinctive and
      not emphasized previously. Ductal/tubular differentiation, prominent desmoplastic
      stromal component, neutrophilic infiltration and the presence of numerous tubules
      ranging from benign to dysplastic and frankly malignant were notable features of
      this tumor. The expression of high-molecular-weight cytokeratin and Ulex
      europaeus agglutinin helped to confirm the diagnosis. CONCLUSION: The present
      case highlights several characteristic cytologic features that were useful in
      suggesting the diagnosis of CDC on fine needle aspiration cytology.
      Immunohistochemical stains, such as high-molecular-weight cytokeratin and lectin,
      helped to confirm the diagnosis.

PMID- 15581172
TI  - Cytologic findings of a pleomorphic adenoma of the breast: a case report.
AB  - BACKGROUND: Pleomorphic adenoma of the breast is a rare benign tumor. Only a few
      cases have been reported. The histologic features have been described well.
      However, the cytologic findings have been described in only a few papers. CASE: A
      47-year-old female presented with a left breast mass of several months' duration.
      The clinical and mammographic findings were highly suspicious for malignancy.
      Following an aspiration biopsy diagnosis of "positive for malignancy," the mass
      was excised. The histologic diagnosis was pleomorphic adenoma (mixed tumor of
      salivary gland type) rather than carcinoma. CONCLUSION: The cytologic
      presentation of pleomorphic adenoma of the breast can masquerade as that of a
      malignant tumor, in this case colloid carcinoma. This case delineates the
      cytomorphologicfeatures of pleomorphic adenoma, which may mimic carcinoma.

PMID- 15581173
TI  - Fine needle aspiration cytology of breast cylindroma in a woman with familial
      cylindromatosis: a case report.
AB  - BACKGROUND: That sweat gland type tumors occur occasionally in the breast is not
      surprising, as the breast and cutaneous sweat glands are embryologically related.
      Cylindromas present most commonly as solitary and sporadic dermal nodules on the
      face and scalp. Cases of multiple cylindromas are dominantly inherited, and the
      neoplasms are referred to as "turban tumors" when multiple lesions cover the
      scalp. Primary cylindroma of the breast has been reported once in the past. To
      the best of our knowledge, the fine needle aspiration cytology of primary breast
      cylindroma and its occurrence in the setting of familial cylindromatosis have not
      previously been reported. CASE: A 59-year-old woman presented with an ill-defined
      left breast mass. She had a personal and family history of dermal cylindromas on
      the head and face. Fine needle aspiration cytology demonstrated small, uniform
      cells with oval nuclei and finely granular cytoplasm, with some cells arranged
      around conspicuous cylinders of dense, acellular material. Excisional biopsy was
      recommended to exclude adenoid cystic carcinoma. Tissue biopsy revealed a benign
      cylindroma arising in breast parenchyma. CONCLUSION: Fine needle aspiration
      cytology of cylindroma very closely mimics that of adenoid cystic carcinoma.
      Although extremely rare, primary breast cylindroma is another entity to be
      included in the cytologic differential diagnosis of bland, basaloid cells
      associated with globular, extracellular material, a finding most commonly
      associated with adenoid cystic carcinoma.

PMID- 15581174
TI  - Aspiration cytology of malignant fibrous histiocytoma after radiation therapy for
      carcinoma of the uterine cervix: a case report.
AB  - BACKGROUND: Cytologic reports on malignant fibrous histiocytoma (MFH) following
      radiation therapy for carcinoma of the uterine cervix are very rare. CASE: A 59
      year-old woman presented with slowly increasing pain in the left hip joint. Eight
      years earlier, she had received radiotherapy at a dosage of 5,000 cGy to the
      whole pelvis for carcinoma of the uterine cervix. An osteolytic lesion of the
      pelvic bone was revealed on computed tomography, and a hard tumor was palpable in
      the left pelvic cavity. Fine needle aspiration (FNA) of the tumor via the left
      vaginal wall obtained 0.5 mL of yellow fluid consisting of markedly anaplastic
      and pleomorphic giant cells. Frequent multinucleation and mitoses were observed,
      although no atypical spindle cells were observed. Immunocytochemistry disclosed
      vimentin reactivity. An open biopsy of the tumor revealed the histologic and
      immunohistochemical features of MFH arising in the pelvic cavity. CONCLUSION: FNA
      of the pelvic lesion via the vaginal wall revealed an MFH in the radiation
      therapy field. This is one of the few reports dealing with FNA cytology of a
      postradiation sarcoma in the pelvic cavity.

PMID- 15581175
TI  - Fine needle aspiration cytology of pleomorphic adenoma of the breast.

PMID- 15581176
TI  - Cytologic findings in a case of metastatic sex cord tumor with annular tubules.

PMID- 15581177
TI  - Ameboma in ultrasound-guided fine needle aspiration.

PMID- 15581178
TI  - Aspergillosis of the thyroid gland diagnosed by fine needle aspiration cytology.

PMID- 15581179
TI  - Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1
      associated peripheral nerve sheath tumors. I. The role of tumor suppressor
      mutations.
AB  - Patients with neurofibromatosis type 1 (NF1), a common autosomal dominant tumor
      predisposition syndrome, develop benign cutaneous, intraneural, and plexiform
      neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs), an
      aggressive form of Schwann cell neoplasm that frequently arises from plexiform
      neurofibromas. Impressive advances have been made in defining the molecular
      mechanisms responsible for neurofibroma and MPNST tumorigenesis, including the
      identification of key tumor suppressor gene mutations, an improved understanding
      of the functions of these tumor suppressors, and the production of transgenic
      mouse models in which tumor suppressor gene mutations predispose animals to the
      development of neurofibromas and MPNSTs. It has also become apparent that
      dysregulated growth factor signaling cooperates with tumor suppressor mutations
      to promote neurofibroma and MPNST tumorigenesis. In Part I of this two-part
      review, we consider findings demonstrating that Schwann cells are the primary
      neoplastic cell type in neurofibromas and MPNSTs and that specific tumor
      suppressor gene mutations promote the development of these tumors. In Part II,
      which will be published in a later issue, we will review evidence indicating that
      inappropriate growth factor signaling contributes to this process by stimulating
      the proliferation, survival, and migration of Schwann cells whose regulatory
      mechanisms have been crippled by a loss of tumor suppressor function.

PMID- 15581180
TI  - JC virus early protein detection by immunohistochemistry in progressive
      multifocal leukoencephalopathy: a comparative study with in situ hybridization
      and polymerase chain reaction.
AB  - In situ hybridization (ISH) for JC virus (JCV) is generally applied for the
      diagnosis of progressive multifocal leukoencephalopathy (PML). To explore the
      usefulness of immunohistochemistry (IHC) for JCV early proteins, 14 paraffin
      embedded postmortem brain specimens with histologic features compatible with PML
      were tested for the presence of JCV by means of DNA-DNA ISH with a biotinylated
      probe corresponding to the entire JCV genome, for JCV early proteins IHC with
      both PAb 2003 and anti-SV40 large T antigen monoclonal antibodies, and polymerase
      chain reaction (PCR) amplification of JCV virion protein 3 (VP3) and
      transcriptional control region (TCR) sequences. ISH was positive in 13 cases and
      IHC in all 14 cases, the number of IHC-positive cells generally being far in
      excess of ISH-positive cells. Of the 2 monoclonal antibodies used, PAb 2003
      proved to be more sensitive than anti-SV40 large T antigen. Occasional neuronal
      nuclei were positive for JCV early proteins in 5 cases. As for PCR, VP3 was
      amplified in all 14 cases and TCR in 9 cases. Consequently, PAb 2003 IHC for JCV
      early proteins seems to be a powerful tool for viral demonstration in PML and may
      well become the diagnostic recourse of choice in this setting.

PMID- 15581181
TI  - Effects of exposure to chronic placental insufficiency on the postnatal brain and
      retina in sheep.
AB  - Chronic placental insufficiency (CPI) has the potential to affect fetal brain
      development and to cause brain injury. Our aim was to determine the effects of
      exposure to CPI during late gestation on brain and retinal structure and brain
      neurotrophin expression 8 weeks after birth. Six fetal sheep were exposed to CPI,
      induced by umbilico-placental embolization, from 120 days of gestation until term
      (approximately 147 days) such that fetal arterial oxygen saturation (SaO2) was
      reduced by approximately 50%. Nine untreated animals served as controls. During
      CPI, fetal arterial PO2, SaO2, pH, and growth were reduced (p < 0.05); these
      animals remained small at 8 weeks after birth. Structural abnormalities were
      present in the brains and retinae of all CPI-exposed lambs. There was a reduction
      in retinal width and in the number of retinal tyrosine hydroxylase-immunoreactive
      dopaminergic amacrine cells (p < 0.05). In the dorsal hippocampus the combined
      width of strata oriens and pyramidale was significantly reduced (p < 0.05). In
      the cerebellum there was a significant reduction (p = 0.05) in cerebellar cross
      sectional area, most notably in the inner granule cell layer, and a reduction (p
      < 0.05) in immunoreactivity for the cytoskeletal protein neurofilament-200 in the
      white matter. Gliosis was present in either the cerebral white matter or
      cerebellum in all animals and degeneration was seen around blood vessels in 4/6
      umbilico-placental embolization animals. There were reductions in brain-derived
      neurotrophic factor immunoreactivity in the hippocampus (p < 0.05) and tyrosine
      kinase B immunoreactivity in the cerebellum (p < 0.05). This study shows that
      late gestational CPI affects morphology and neurotrophin expression of the
      postnatal brain. These alterations in the brain can apparently persist from fetal
      life or become established after birth; some changes that were present in the
      fetus at term did not persist into postnatal life.

PMID- 15581182
TI  - Ganglion-specific patterns of diabetes-modulated gene expression are established
      in prevertebral and paravertebral sympathetic ganglia prior to the development of
      neuroaxonal dystrophy.
AB  - In both humans and animal models, diabetic sympathetic autonomic neuropathy is
      associated with the selective development of markedly enlarged distal axons and
      nerve terminals (neuroaxonal dystrophy, NAD). NAD occurs in the prevertebral
      superior mesenteric and celiac ganglia (SMG-CG), but not in the paravertebral
      superior cervical ganglion (SCG). To identify molecular differences between these
      ganglia that may explain their selective vulnerability to NAD, we have examined
      global gene expression patterns in control and diabetic rat sympathetic ganglia
      before and after the onset of structural evidence of NAD. As predicted, major
      differences in transcriptional profiles exist between SCG and SMG-CG in normal
      young adult animals including, but not limited to, known differences in
      neurotransmitter-related gene expression. Gene expression patterns of diabetic
      SMG-CG and SCG, prior to the development of NAD lesions, also differ from their
      age-matched non-diabetic counterparts. However, diabetes has ganglion-specific
      effects on gene expression; of approximately 110 transcripts that were
      differentially expressed between diabetic and control sympathetic ganglia, only 5
      were differentially expressed as a result of diabetes in both SCG and SMG-CG.
      Genes involving synapse and mitochondrial structure and function, oxidative
      stress, and glycolysis were highly represented in the differentially expressed
      gene set. Differences in the number of synapse-related gene alterations in
      diabetic SMG-CG (18 genes) versus SCG (2 genes) prior to the onset of NAD may
      also well explain the selective development of NAD in the SMG-CG. These results
      provide support for the specificity of diabetes-modulated gene expression for
      selected neuronal subpopulations of sympathetic noradrenergic neurons.

PMID- 15581183
TI  - Human wild-type alpha-synuclein impairs neurogenesis.
AB  - Neurodegenerative diseases classified as synucleinopathies are characterized by
      alpha-synuclein inclusions. In these disorders, alpha-synuclein accumulates
      within glial or neuronal cells in the brain including regions of adult
      neurogenesis. We hypothesized a pathophysiological role for alpha-synuclein in
      newly generated cells of the adult brain and in this study examined regions of
      neurogenesis in adult mice overexpressing human wild-type alpha-synuclein under
      the control of the platelet-derived growth factor promoter. The number of
      proliferating cells and the fate of newly generated cells were analyzed in the
      olfactory bulb system and in the hippocampal dentate gyrus. There were no effects
      on proliferation detectable; however, significantly less neurogenesis and fewer
      neurons were observed in the olfactory bulb as well as in the hippocampus of
      adult human alpha-synuclein mice compared to control littermates. This effect was
      almost exclusively due to diminished survival of neuronal precursors in the
      target regions of neurogenesis. Our data imply that the finely tuned equilibrium
      of neuronal cell birth and death in neurogenic regions may be altered in human
      alpha-synuclein-overexpressing mice. We hypothesize that reduced adult
      neurogenesis in the olfactory bulb may contribute to olfactory deficits in
      neurodegenerative disorders associated with alpha-synuclein inclusions.

PMID- 15581184
TI  - Peripheral nerve biopsy study in 19 cases with 17p11.2 deletion.
AB  - In most cases of hereditary neuropathy with liability to pressure palsy (HNPP)
      the diagnosis is now assessed by molecular detection of 17p11.2 deletion.
      However, the family history may be missing and the clinical presentation is not
      always informative. In such cases, a peripheral nerve biopsy showing the
      characteristic focal myelin sheath thickening ("tomaculae") may be helpful. We
      present a retrospective study of peripheral nerve biopsies performed in 19
      patients suffering from either a mononeuropathy or a generalized sensory-motor
      polyneuropathy, and for whom the finding of tomaculae led to a search for 17p11.2
      deletion, which was confirmed secondarily. Tomaculae and other coexisting
      neuropathological lesions such as uncompacted myelin, "onion bulb" formations,
      and axonal degeneration are described and discussed in the view of previously
      reported data. It appears that demyelinating lesions with tomaculae are strongly
      suggestive of HNPP but are not specific as they may be observed in other
      conditions. Moreover, these features may be overlooked if axonal degeneration is
      marked.

PMID- 15581185
TI  - Chronic granulomatous herpes simplex encephalitis in children.
AB  - Herpes simplex encephalitis is usually a monophasic acute illness but can cause
      chronic disease, particularly in children. Little information is available as to
      the histological substrate. We report the findings in 3 children. In 2 children,
      herpes encephalitis had occurred during the first 2 years, but both later
      developed intractable epilepsy that led to neurosurgery. The biopsies showed
      chronic granulomatous inflammation with foci of mineralization. One child made a
      good post-operative recovery. The other was found post-operatively to have herpes
      simplex virus type 1 (HSV-1) DNA and elevated titers of HSV IgM antibodies in the
      CSE He was given acyclovir but after initial improvement developed hemiparesis,
      with extensive signal change on MRI. Repeat biopsy revealed florid granulomatous
      inflammation with necrosis. The third patient was an infant who had had a
      cutaneous facial HSV-2 eruption soon after birth. This was treated with topical
      acyclovir, after which she remained well until 2 months, when she presented with
      a relatively non-specific illness, developed blisters of the right hand and foot,
      and died a few days later. Necropsy revealed severe granulomatous encephalitis,
      most extensive in the temporal lobe and insula, and associated with
      mineralization. Our findings indicate that herpes simplex encephalitis in
      children can be complicated by chronic granulomatous inflammation with
      mineralization. This pattern of disease may be an under-recognized complication
      of herpes simplex infection during the first few years of life.

PMID- 15581186
TI  - Physiology and gene expression characteristics of carcinogen-initiated and tumor
      transformed glial progenitor cells derived from the CNS of methylnitrosourea
      (MNU)-treated Sprague-Dawley rats.
AB  - Glial progenitors from the brain of normal adult Sprague-Dawley rats were
      compared to their initiated and malignant counterparts that were isolated from
      apparently normal brains of animals exposed to methylnitrosourea (MNU).
      Fibroblast growth factor-2 (FGF-2) or platelet-derived growth factor (PDGF)-A or 
      B induced differentiation of normal progenitors to a pro-astrocytic or
      oligodendrocytic morphology, respectively, whereas the combination of these
      factors resulted in their terminal differentiation to oligodendrocytes and
      senescence. In contrast, initiated progenitors did not exit the cell cycle when
      stimulated with PDGF and/or FGF-2. cDNA oligoarray analysis and RT-PCR
      verification showed an early upregulation/ induction of growth factor/receptors,
      PDGF-A, PDGFR-beta, IGFR-1, IGF-1 and -2, IL-6, MEGF-5, FRAG-1, IRS-2, HSPG, and
      FGFR-1, followed by a late increase in the expression IGFBP-6, PDGF-alpha, FGFR
      4A, c/ERB-A, and FGFR-4, 2, and 1 during the tumorigenic progression. Western
      blot analyses demonstrated that MNU exposure caused progressive reduction of p21
      protein levels, an increase of Rb phosphorylation, activation of AKT and CDK2,
      and upregulation of FGF receptors. Double immunofluorescence labeling showed
      progressive increase in nuclear colocalization of FGFR1, 2, and 4, which peaked
      in malignant lines. It is postulated that transition of normal rat glial
      progenitors to an initiated state is driven by IGF-1 and 2, IL-6, and the
      upregulation of the receptors PDGFR-beta and FGFR-1, 2, and 4. Deregulation of
      the cell cycle in this state involves reduction of p21 protein, concomitant
      upregulation of CDC2, and an increase in Rb phosphorylation that favors
      expression and nuclear translocation of FGFR-4 and FRAG-1 and 2. These events are
      associated with progressive activation of AKT and RAS. Malignant transformation
      is enhanced by near elimination of p21 and PC3, induction of AP-1 (upregulation
      of JUN-B, c-JUN, FRA-1), activation of the NF-kB pro-survival pathway, and
      inhibition of the TGF-beta pro-apoptotic pathway possibly in response to changes
      in the expression of nerve growth factor (NGF) I-A and NGFI-B. These data
      demonstrate that the events leading to malignancy in the rat brain in response to
      MNU treatment are to a great extent similar to those described for secondary
      glial malignancies in humans.

PMID- 15581187
TI  - Intranuclear rodlets in the substantia nigra: interactions with marinesco bodies,
      ubiquitin, and promyelocytic leukemia protein.
AB  - There is growing appreciation that the nucleus is organized into an array of
      discrete structural domains, each subserving a specific function. These
      functional nuclear bodies are to be distinguished from pathological intranuclear
      inclusions which have been described in a variety of neurodegenerative diseases.
      Marinesco bodies (MBs) are eosinophilic ubiquitinated intranuclear inclusions
      found in pigmented neurons of the human substantia nigra and locus coeruleus.
      Traditionally considered non-pathological entities, more recent studies have
      indicated that MBs are associated with the age-associated degenerative changes in
      the substantia nigra and striatal loss of dopaminergic terminals. In the present
      morphological study of the human substantia nigra, we demonstrate colocalization,
      contiguity, and focally shared immunoreactivity between MBs and neuronal
      intranuclear rodlets (INRs). The latter nuclear structures of uncertain function
      are markedly decreased in the cortex of Alzheimer's disease, but not dementia
      with Lewy bodies. In addition, we demonstrate an interaction between INRs and
      promyelocytic leukemia (PML) protein, the signature protein of PML nuclear
      bodies. These results suggest that structures which subserve the functional
      compartmentalization of the neuronal nucleus may be relevant to elucidating
      cellular mechanisms of age-related motor dysfunction.

PMID- 15581188
TI  - Perception of Mandarin lexical tones when F0 information is neutralized.
AB  - In tone languages, the identity of a word depends on its tone pattern as well as
      its phonetic structure. The primary cue to tone identity is the fundamental
      frequency (F0) contour. Two experiments explore spoken word recognition how
      listeners perceive Mandarin monosyllables in which all or part of the F0
      information has been neutralized. In Experiment 1, tone languages supposedly
      critical portions of the tonal pattern were neutralized with signal processing
      techniques, yet identification of the tonal pattern remained quite good. In
      Experiment 2, even more drastic removal of tonal information was tested, using
      stimuli whispered by Mandarin speakers, or signal processed to remove the pitch
      cues. Again, performance was surprisingly good, showing that listeners can use
      secondary cues when the primary cue is unavailable. Moreover, a comparison of
      tone perception of naturally whispered monosyllables and the signal processed
      ones suggests that Mandarin speakers promote the utility of secondary cues when
      they know that the primary cue will be unavailable. The flexible use of cues to
      tone in Mandarin is similar to the flexibility that has been found in the
      production and perception of cues to phonetic identity in Western languages.

PMID- 15581189
TI  - Effects of noise and proficiency on intelligibility of Chinese-accented English.
AB  - This study compared the intelligibility of native and foreign-accented
      bilingualism English speech presented in quiet and mixed with three different
      levels of background noise. Two native American English speakers and four native
      Mandarin Chinese speakers for whom English is a second language each read a list
      of 50 phonetically balanced sentences (Egan, 1948). The authors speech
      intelligibility identified two of the Mandarin-accented English speakers as high
      proficiency speakers and two as lower proficiency speakers, based on their speech
      intelligibility in quiet (about 95% and 80%, respectively). Original record
      perception ings and noise-masked versions of 48 utterances were presented to
      monolingual American English speakers. Listeners were asked to write down the
      words they heard the speakers say, and intelligibility was measured as content
      words correctly identified. While there was a modest difference between native
      and high-proficiency speech in quiet (about 7%), it was found that adding noise
      to the signal reduced the intelligibility of high-proficiency accented speech
      significantly more than it reduced the intelligibility of native speech.
      Differences between the two groups in the three added noise conditions ranged
      from about 12% to 33%. This result suggests that even high-proficiency non-native
      speech is less robust than native speech when it is presented to listeners under
      suboptimal conditions.

PMID- 15581190
TI  - Vowel production and perception: hyperarticulation without a hyperspace effect.
AB  - The ability of speakers to exaggerate speech sounds ("hyperarticulation") has led
      to the theory that the targets themselves must be hyperspace hyperarticulated.
      Johnson, Flemming, and Wright (1993) found that perceptual "best exemplar"
      choices for vowels were more speech extreme than listeners' own productions. Our
      first experiment, using their procedure, only partially replicated their results.
      Low vowels vowel perception showed a higher F1, consistent with hyperspace. Front
      vowels also showed more frontness in F2, but back vowels were less extreme
      ("hypoarticulated") on F2. Our second experiment used an identification and
      rating of each stimulus, yielding similar results of a smaller magnitude. Our
      results indicate that the perceptual space is calibrated to a particular
      (synthetic) vowel space, which is not related straightforwardly to the speakers'
      spaces. The original hyperspace hypothesis can be attributed to the methodology
      which led to extreme judgments and of the fronting of back vowels in California
      English. The present results indicate that no such hypothesis is needed. Vowel
      targets are measurable from an individual's productions, and the individual's
      perception of other speakers (even synthetic ones) is based on information about
      the vocal tract and dialect of the speaker.

PMID- 15581191
TI  - Recognition of spoken words: semantic effects in lexical access.
AB  - Until recently most models of word recognition have assumed that semantic
      auditory naming effects come into play only after the identification of the word
      in question. What little evidence exists for early semantic effects in word
      recognition lexical decision has relied primarily on priming manipulations using
      the lexical decision task, and has used visual stimulus presentation. The current
      study uses semantics auditory stimulus presentation and multiple experimental
      tasks, and does not use priming. Response latencies for 100 common nouns were
      found to speech perception depend on perceptual dimensions identified by Osgood
      (1969): Evaluation, Potency, and Activity. In addition, the two-way interactions
      between these word recognition dimensions were significant. All effects were
      above and beyond the effects of concreteness, word length, frequency, onset
      phoneme characteristics, stress, and neighborhood density. Results are discussed
      against evidence from several areas of research suggesting a role of behaviorally
      important information in perception.

PMID- 15581192
TI  - Danger in the (farm) dust.

PMID- 15581193
TI  - Report on the meeting of the Second Ad Hoc Committee on the TB epidemic:
      recommendations to Stop TB Partners, Montreux, Switzerland, 18-19 September 2003.

PMID- 15581194
TI  - High risk of adult-onset asthma and work-related wheeze in farmers despite low
      prevalence of asthma in young farmers.
AB  - OBJECTIVE: To investigate risk factors for asthma in farmers. METHODS: A
      questionnaire was sent to all farms (n = 2499) and to 2900 controls aged 19-65
      years from the general population in the county of Uppsala. Sixty per cent of the
      farms (1514 men and 248 women) and 64% of the controls (900 men, 943 women)
      responded. RESULTS: Only 13% of the male farmers had heredity for allergy
      compared to 24% of the controls, and fewer farmers were smokers. After adjusting
      for confounders, male farmers had a significantly lower prevalence of doctor
      diagnosed asthma and nocturnal breathlessness than the controls (OR 0.75, 95%CI
      0.57-0.98 and OR 0.61, 95%CI 0.44-0.84), but a significantly higher prevalence of
      work-related wheeze (OR 1.74, 95%CI 1.30-2.35). The risk for asthma increased
      with age in the farmers. Of male farmers with asthma, 70% had developed asthma
      after the age of 21, in contrast with only 30% of the asthmatic controls. The
      young female farmers had a high prevalence of asthma. CONCLUSION: Male farmers
      have an increased risk of work-related wheeze and adult-onset asthma increasing
      with age despite a lower prevalence of asthma during childhood and young age than
      in the general population.

PMID- 15581195
TI  - Low socio-economic status is a risk factor for respiratory symptoms: a comparison
      between Finland, Sweden and Estonia.
AB  - OBJECTIVE: To assess the relation of socio-economic status to respiratory
      symptoms common in asthma and chronic bronchitis, and to compare risk factors for
      these symptoms between three neighbouring countries. DESIGN: A postal survey was
      performed in 1996 as a part of comparative studies in Finland, Sweden and Estonia
      (the FinEsS studies). A random sample of 58,661 subjects aged 20-64 years were
      invited, of whom 44,483 participated. RESULTS: Respiratory symptoms were most
      prevalent among manual workers, who were at significantly increased risk for
      chronic respiratory symptoms. The same pattern of increased risk appeared when
      the analyses were made among non-smokers only: for recurrent wheeze, manual
      workers in industry yielded an OR of 1.91 (95%CI 1.62-2.24) and in the service
      sector an OR of 1.50 (95%CI 1.27-1.78). The corresponding figures for chronic
      productive cough were 1.45 (95%CI 1.22-1.71) and 1.20 (95%CI 1.02-1.42),
      respectively. Risk factor profiles for respiratory symptoms were similar in
      Finland, Sweden and Estonia, except for gender differences in Estonia.
      CONCLUSIONS: Belonging to the socio-economic group of manual workers correlated
      with an increased risk for chronic respiratory symptoms, independently of smoking
      habits, in each country. Women manual workers in industry suffered most from
      respiratory symptoms.

PMID- 15581196
TI  - Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid
      therapy.
AB  - SETTING: While exhaled nitric oxide (eNO) levels are reduced by inhaled
      corticosteroid therapy in asthma, such treatment effect is unclear in
      bronchiectasis. DESIGN: Stable non-smoking bronchiectasis patients were
      randomised to receive either fluticasone (1 mg/daily) or identical placebo via
      the Accuhaler device. RESULTS: Sixty non-smoking patients (38 women; mean age
      56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone
      and half placebo therapy. eNO was measured using a chemiluminescence analyser at
      0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels
      between fluticasone and placebo patients over the study period. There was no
      correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or
      number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA)
      infection, but not their counterparts, displayed a correlation between 0- and 52
      week eNO levels. PA infection was associated with significantly lower eNO levels
      among the patients. CONCLUSIONS: Inhaled fluticasone therapy, despite being an
      effective anti-inflammatory agent, has no significant effect on eNO production,
      either at individual time points or over the entire 52-week profile, in
      bronchiectasis. It appears that eNO might not reflect the extent of airway
      inflammation in bronchiectasis.

PMID- 15581197
TI  - Comparison of clinical outcome with oral and inhaled bronchodilators in the
      management of wheezy children aged 1-59 months in the community: a randomised
      trial in Pakistan.
AB  - BACKGROUND: Wheeze is a significant problem in children. There is a gradual trend
      of switching from oral to inhaled bronchodilator therapy. No randomised trials
      have been carried out in the community to compare the clinical outcome of two
      modes of therapy. If outcome with oral and inhaled bronchodilators is the same in
      young wheezers in developing countries, it will be easier to manage them.
      METHODS: In a randomised multicentre trial, wheezy children aged 1-59 months with
      fast breathing and/or lower chest indrawing received oral or inhaled salbutamol
      at home after responding to up to three cycles of inhaled bronchodilators. They
      were re-assessed on days 3 and 5 for clinical outcome. RESULTS: From May 2001 to
      August 2002, 780 children were enrolled; 390 each were randomised to oral and
      inhaled salbutamol. On day 5, 324 (83.1%) children in the oral and 328 (84.1%) in
      the inhaled group were completely well. There were no differences in clinical
      outcome of both modes of therapy. CONCLUSIONS: The clinical outcome of children
      aged 1-59 months with wheeze is similar when treated with oral or inhaled
      salbutamol. Acute respiratory infection control programmes in developing
      countries should continue to use oral bronchodilators for the management of
      wheeze to save both time and money.

PMID- 15581198
TI  - The impact of altitude on mortality from tuberculosis and pneumonia.
AB  - OBJECTIVE: To examine the association between altitude and mortality from
      tuberculosis (TB) and pneumonia-influenza in Mexico. DESIGN: We analysed specific
      causes of death in Mexico according to death certificates for the period 1993
      1997, totalling over 2,700,000 deaths and including nearly 23,000 attributed to
      TB and 115,000 to pneumonia and influenza. Thirty population subgroups were
      formed based on altitude of residence (six categories) and level of poverty (five
      categories). The effect of altitude on mortality was estimated through Poisson
      regression models, with adjustment for age, gender and socioeconomic status.
      RESULTS: Adjusted death rates for TB decreased with altitude and increased for
      pneumonia-influenza. Compared to people living below 500 m above sea level, those
      living between 2000 and 2499 m had a 58% mortality rate for TB and a three-fold
      increase in mortality due to pneumonia-influenza, despite adjustment for poverty,
      age and gender. CONCLUSION: The mortality rate for TB based on death certificates
      decreases with altitude of residence, whereas the opposite is observed for
      pneumonia and influenza.

PMID- 15581199
TI  - Effect of altitude on the frequency of pulmonary tuberculosis.
AB  - SETTING: Pulmonary tuberculosis (PTB) incidence greatly varies around the world,
      a phenomenon usually attributed to socio-economic factors or health service
      availability. A recent study, however, indicated that PTB was inversely related
      to altitude. OBJECTIVE: To evaluate factors associated with PTB notification
      rates in Mexico. METHODS: Annual notification rates (1998-2002) of PTB in each of
      the 32 Mexican states were analysed, and likely factors were assessed through
      correlation and multiple regression analyses. RESULTS: Most variables lacked
      association with PTB rates, including percentage of population aged > or = 65
      years, population density, percentage of population with < or = 2 minimum
      salaries, percentage of population with social security, level of education,
      diabetes incidence, percentage of immigration, percentage of rural population and
      a global marginalisation index. Only altitude above sea level correlated with
      tuberculosis incidence (r = -0.74, P < 0.0001). Likewise, in the multiple
      regression analysis only altitude reached a statistically significant
      association. CONCLUSION: Our results showed that altitude had a strong inverse
      relationship to PTB notification rates in Mexico, which might be related to the
      well known changes in alveolar oxygen pressure at different altitudes.
      Interestingly, several factors traditionally considered as predisposing
      conditions for the development of PTB did not correlate with the disease.

PMID- 15581200
TI  - Tuberculosis control and the private health sector in Bolivia: a survey of
      pharmacies.
AB  - BACKGROUND: Bolivia is a high tuberculosis (TB) incidence country with a large
      private for-profit health sector. TB drug sales in private pharmacies are not
      illegal. OBJECTIVES: To measure the availability of TB drugs in private
      pharmacies, study vendors' attitudes, and explore the potential for collaboration
      between the public health sector and pharmacies. METHODS: Simulated clients
      visited a random sample of 100 pharmacies in the city of Cochabamba, presenting
      with a prescription for four TB drugs. After the survey, contacts were made with
      the local Pharmacist's Association. RESULTS: Twenty-five pharmacies sold at least
      one drug, 23 sold rifampicin and 16 sold isoniazid. Of 99 pharmacies unable to
      fill the whole prescription, 59 referred the client to another pharmacy, and 22
      to the public services. Pharmacists said that rifampicin was often prescribed for
      non-TB indications, and that TB drug sales were of minimal contribution to their
      income. They agreed to stop selling the drugs and to refer clients seeking them
      to the public sector. CONCLUSION: This study has documented a small market for TB
      drugs sales in private pharmacies and provided the opportunity to start
      collaboration with the pharmacists. Our results suggest that the private sector
      contributes little to managing TB in Bolivia.

PMID- 15581201
TI  - The cost of medical care and people's health-seeking behaviour before being
      suspected of tuberculosis in three local health systems, Nicaragua.
AB  - OBJECTIVE: To assess the medical costs incurred by users and delay between first
      contact with a care provider and sputum test for acid-fast bacilli (AFB) in three
      areas of Nicaragua. METHODS: Directed interviews of consecutive series of
      tuberculosis (TB) suspects whose sputum had been examined for AFB. RESULTS: Of
      252 TB suspects interviewed, 52% used more than one type of care giver and 35%
      used private practitioners. As a consequence, 18%, 21% and 29% of the
      interviewees in Carazo, El Viejo and Matagalpa, respectively, spent more than 1
      month of the country's median income per inhabitant on medical care between the
      first visit to a care provider and the first sputum examination. Furthermore,
      more than 3 months elapsed on that part of the care pathway for 30%, 17% and 3%
      of interviewees in Matagalpa, El Viejo and Carazo, respectively. CONCLUSION: This
      study sheds light on the costs and delays incurred by TB suspects before reaching
      a laboratory for sputum smear examination. Both costs are lower for those
      suspects who exclusively use first-line governmental health services (FLGHS).
      This has been relatively little documented in Latin America to date and could be
      used as an argument to develop strategies to strengthen the credibility of FLGHS.

PMID- 15581202
TI  - Tuberculosis treatment default at the communicable diseases unit of Effia-Nkwanta
      Regional Hospital: a 2-year experience.
AB  - SETTING: Effia-Nkwanta Regional Hospital, located at Sekondi-Takoradi, the
      capital and third largest city of the Western Region of Ghana. OBJECTIVE: To
      examine factors associated with treatment default among tuberculosis (TB)
      patients registered for treatment in 2000-2001. DESIGN: Retrospective review of
      institutional records of TB patients. METHOD: The database for registered TB
      patients was sorted out into the six treatment outcomes. Five outcomes were
      combined into one variable named 'non-defaulters' and were compared with
      defaulters. Statistical significance was taken as P < 0.05. RESULTS: The
      defaulter rate for all categories of patients was 13.9%. Default from treatment
      was significantly associated with male sex, smear positivity and living in
      communities far from the treatment centre. Patients in the 25-44 year age group
      and those put on the retreatment regimen have higher defaulter rates, but these
      were not statistically significant when compared to non-defaulters. The mean
      defaulting moment was 3.4 months. The overall probability of a patient remaining
      on treatment 5 months after starting was 3.6%. CONCLUSION: Treatment centres
      should be sited near the patients to improve access. Further studies are needed
      to identify the barriers for patients in completing their treatment.

PMID- 15581203
TI  - Comparison of two bacteriophage tests and nucleic acid amplification for the
      diagnosis of pulmonary tuberculosis in sub-Saharan Africa.
AB  - SETTING: National reference laboratory in Zambia, a high-incidence setting with a
      high prevalence of HIV infection. OBJECTIVE: To compare the performance of a
      commercial bacteriophage kit with a nucleic acid amplification kit and an 'in
      house' bacteriophage method for rapid diagnosis of pulmonary tuberculosis (TB).
      METHODS: Sputum specimens from suspected pulmonary TB cases were examined by
      direct fluorescence microscopy and culture on Lowenstein Jensen (LJ). In a
      blinded study, remaining samples were tested by AMTD and FASTPlaqueTB or an in
      house bacteriophage assay. Two specimen decontamination protocols were
      investigated. RESULTS: Microbial contamination of 40.4% was observed when using
      the FASTPlaqueTB kit specimen preparation protocol. When compared to culture on
      LJ, the sensitivity of the FASTPlaqueTB test was 20.7%. Implementation of a
      modified Petroff's decontamination protocol reduced contamination to 5.8% and the
      FASTPlaqueTB test detected 8/25 (32%) of culture-positive specimens. The
      sensitivity of AMTD and smear microscopy for these specimens were 64% and 48%,
      respectively. In a separate experiment the sensitivity of an in-house
      bacteriophage assay was 45.3% compared to 64.2% for AMTD and 45.3% for direct
      smear microscopy. CONCLUSIONS: Additional analysis of sputum specimens by
      bacteriophage assay provided no advantage in this setting. For the rapid
      diagnosis of TB, AMTD offered improved sensitivity over direct smear microscopy.

PMID- 15581204
TI  - Effect of Mycobacterium vaccae (SRL172) immunotherapy on radiographic healing in
      tuberculosis.
AB  - OBJECTIVE: Controlled trials have failed to show an effect of Mycobacterium
      vaccae immunotherapy on treatment outcome and mortality in patients with
      tuberculosis (TB); however, several studies have suggested improvement in
      radiographic clearing and resolution of cavitary disease. METHODS: To assess the
      effect of M. vaccae immunotherapy on radiographic healing in pulmonary TB, chest
      X-rays from three randomized placebo-controlled trials of M. vaccae given as a
      single injection during the first 2 weeks of treatment were interpreted by a
      single, masked assessor using a standard scheme. Endpoints were the overall
      degree of radiographic improvement or deterioration and changes in cavitary
      disease at the end of antituberculosis treatment and follow-up. RESULTS: Of 1018
      patients (478 HIV-infected; 540 HIV-uninfected) with an end of treatment or end
      of follow-up X-ray analyzed, 496 received M. vaccae and 522 received placebo.
      There was no difference in radiographic improvement or deterioration or cavitary
      disease at the end of treatment or follow-up comparing the M. vaccae and placebo
      groups. Results were similar comparing HIV-infected and HIV-uninfected patients.
      CONCLUSION: Adjunctive immunotherapy of drug-susceptible pulmonary TB with M.
      vaccae during the first 2 weeks of treatment did not improve radiographic
      responses to treatment or resolution of cavitary disease.

PMID- 15581205
TI  - Health-seeking patterns among Chinese immigrant patients enrolled in the directly
      observed therapy program in New York City.
AB  - SETTING: Outreach services and chest clinics of the Department of Health in New
      York City. OBJECTIVE: To investigate the health-seeking behavior patterns of
      Chinese immigrant patients enrolled in the directly observed therapy (DOT)
      program in New York City, and to suggest service provision strategies. DESIGN:
      Data were collected by means of participant observation, semi-structured
      interviews, and patient narratives. These data were then analyzed statistically
      as well as qualitatively, based on grounded theory. RESULTS: Of 60 patient
      informants, 38 had sought treatment for the relief of symptoms, and 22 were
      diagnosed by physical examination. Among 125 consultations made by 38 symptomatic
      patients during the period of their illness, there were more Chinatown
      physicians, including traditional Chinese practitioners, than other types of
      health providers, but they proportionally made the fewest referrals to the DOT
      program. CONCLUSIONS: Chinatown physicians are the main health providers to whom
      Chinese immigrants with tuberculosis resort. Education and collaboration with
      Chinese doctors, practitioners of both biomedical and traditional Chinese
      medicine, in New York City's Chinatown, are essential to reduce enrolment delays
      in the DOT program. The free services of the DOT program should be made more
      widely known to the Chinese immigrant population.

PMID- 15581206
TI  - Pharmacokinetics of ethambutol in children and adults with tuberculosis.
AB  - SETTING: Five hospitals in the United States. OBJECTIVE: To describe ethambutol
      pharmacokinetics in children and adults with active tuberculosis (TB). DESIGN:
      Prospective, open-labeled study in 56 adults and 14 children with active
      tuberculosis who received ethambutol as part of their multidrug TB regimens.
      RESULTS: Most serum samples were collected up to 10 h post dose and assayed using
      a validated gas chromatography assay with mass selective detection (GC/MS).
      Concentration data were analyzed using non-compartmental and population
      pharmacokinetic methods. Drug exposure increased with dose, but less than
      proportionally at doses >3000 mg. Lower than expected maximum serum
      concentrations (Cmax <2 microg/ml) were common in adults. Very low Cmax (<1
      microg/ml) were common in children, as was delayed absorption (time to Cmax >3
      h). Many Cmax were at or below typical TB minimal inhibitory concentrations. Cmax
      values for HIV-positive patients were 20% lower than HIV-negative patients with
      daily doses, but were similar with larger twice-weekly doses. CONCLUSIONS: Adult
      TB patients often had lower than expected ethambutol serum concentrations, and
      most pediatric TB patients had very low ethambutol serum concentrations. Higher
      doses and therapeutic drug monitoring may be indicated for many of these
      patients.

PMID- 15581207
TI  - Penetration of isoniazid, rifampicin and pyrazinamide in tuberculous pleural
      effusion and psoas abscess.
AB  - SETTING: Tuberculosis Centre, University Medical Centre, Groningen, The
      Netherlands. OBJECTIVES: To study intralesional concentrations of isoniazid
      (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions
      and psoas abscesses, and to compare these to reference serum values and minimal
      inhibitory concentration (MIC). DESIGN: Intralesional concentrations were
      measured 2 h after drug administration (six pleural effusions, 10 psoas
      abscesses). RESULTS: A wide range of concentrations was found for pleural
      effusions and psoas abscesses. Concentrations were below MIC values in none of 15
      patients for INH, in two of 13 for RMP, and in eight of nine for PZA. The
      Cmax:MIC ratio was always >4 for INH, in four of 13 for RMP, and in none of nine
      for PZA. In 5/8 patients receiving all three drugs, both RMP and PZA had Cmax:MIC
      ratios <4, indicating sub-therapeutic drug levels. CONCLUSION: Penetration of INH
      was always sufficient, penetration of RMP mostly below the desired ratio, and for
      PZA on average 10 times too low. Five of eight patients on all three drugs had
      Cmax:MIC ratios <4. This indicates intralesional sub-therapeutic drug levels for
      RMP and PZA, and local monotherapy with INH. This could induce drug resistance.
      Drainage as additional therapy seems indicated.

PMID- 15581208
TI  - Unchanged acetylation of isoniazid by alcohol intake.
AB  - SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the
      pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the
      hypothesis that alcohol increases the conversion of INH by acetylation into its
      metabolite acetylisoniazid. DESIGN: In a crossover design, an oral dose of 300 mg
      INH was administered on 2 separate days, 14 days apart, with or without alcohol
      to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS:
      Neither the metabolism of INH nor that of acetylisoniazid was changed by acute
      alcohol intake. CONCLUSION: Acute alcohol intake has no impact on the conversion
      of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N
      acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH
      metabolism probably contributes little to the therapeutic failure of anti
      tuberculosis treatment among alcoholics.

PMID- 15581209
TI  - Conducting research: practical steps.
AB  - Developing a research protocol and obtaining funding for carrying out the
      research are only the first steps in doing research. Understanding the means to
      conduct the research is equally important. As research is a joint effort of a
      team, a mechanism of collaboration must be developed to engage all those with an
      interest in the research. This includes the community in which the research is to
      be undertaken, representatives of those who will participate in the research, the
      academic community who will be involved in the research, and those who will
      sponsor the research. These individuals can be formed into a 'steering committee'
      to guide the development, conduct, analysis and communication of the research.
      Careful consideration must be given to the benefits and risks of the research.
      These must be precisely spelled out in the research protocol, and all aspects of
      the research must be independently evaluated for technical competence, accuracy,
      communication and liability for injury by an ethics review committee. The
      research must follow precisely the protocol developed. Administrative procedures,
      including recruitment and management of staff, outlining standard procedures and
      quality assurance procedures must be clearly outlined and followed. Carefully
      handling the information collected in a research project is vital to ensuring the
      quality and validity of the research.

PMID- 15581210
TI  - Adverse events in the treatment of multidrug-resistant tuberculosis: results from
      the DOTS-Plus initiative.
AB  - Adverse events associated with second-line drugs have been mentioned as obstacles
      in the management of multidrug-resistant tuberculosis (MDR-TB). Data on adverse
      events were collected from five DOTS-Plus sites in Estonia, Latvia, Peru (Lima),
      the Philippines (Manila) and the Russian Federation (Tomsk Oblast). The results
      show that among 818 patients enrolled on MDR-TB treatment only 2% of patients
      stopped treatment, but 30% required removal of the suspected drug(s) from the
      regimen due to adverse events. The study shows that adverse events are manageable
      in the treatment of MDR-TB in resource-limited settings provided that standard
      management strategies are applied.

PMID- 15581211
TI  - Relationship between self reporting of past history of anti-tuberculosis
      treatment and radiographic findings in multidrug-resistant tuberculosis.
AB  - SETTING: A referral hospital for multidrug-resistant tuberculosis (MDR-TB)
      patients in KwaZulu-Natal, South Africa. OBJECTIVE: To investigate how self
      reporting of past exposure to anti-tuberculosis therapy in MDR-TB patients
      relates to their chest radiographs. RESULTS: Chest radiographs of 406 patients
      with bacteriologically confirmed MDR-TB who were admitted to a tertiary referral
      hospital during 1998-2001 were reviewed. Of 245 patients with chronic
      radiographic changes, 91% reported previous anti-tuberculosis treatment, while of
      161 patients with acute radiographic changes, 70% reported no previous history of
      TB treatment. CONCLUSION: Self-reporting by patients of previous anti
      tuberculosis treatment relates to the duration of disease assessed
      radiologically, and is much more reliable than previously postulated.

PMID- 15581212
TI  - Drug susceptibility of Mycobacterium tuberculosis in HIV-infected and -uninfected
      Ethiopians and its impact on outcome after 24 months of follow-up.
AB  - From a prospective cohort study on tuberculosis/human immunodeficiency virus
      (TB/HIV) interaction in Addis Ababa, Ethiopia, drug susceptibility results were
      available for 94 TB patients (46% HIV-infected). Resistance to one or more
      drug(s) was detected in 21 (22.3%) and multidrug resistance in five (5.3%)
      patients. Occurrence of resistance was not related to HIV status or outcome after
      24 months of follow-up. However, among HIV-infected TB patients who died during
      follow-up, survival time in those with a resistant Mycobacterium tuberculosis
      strain was significantly shorter compared to those with a sensitive strain (6 vs.
      13 months). Early detection of drug resistance and timely treatment change can
      therefore have a positive impact on survival in HIV-infected TB patients.

PMID- 15581213
TI  - Tuberculosis among physicians in training.
AB  - A total of 478 resident doctors working at our hospital were interviewed
      regarding development of tuberculosis after joining the hospital. Nine residents
      had developed tuberculosis, yielding an overall risk of 11.2 cases per 1000
      person-years of exposure. Another 231 resident doctors newly admitted to the
      residency programme over a 1-year period were prospectively followed up over the
      next year. Four residents in this group developed tuberculosis within 1 year of
      joining the hospital, yielding an overall incidence of 17.3/1000. Physicians in
      training have a high risk of developing active tuberculosis after nosocomial
      transmission.

PMID- 15581214
TI  - Cholera, 2002.

PMID- 15581215
TI  - Fourth meeting of the Steering Committee on Immunization Safety conclusions and
      recommendations.

PMID- 15581216
TI  - Global Advisory Committee on Vaccine Safety, 11-12 June 2003.

PMID- 15581217
TI  - Distribution of Salmonella in tissues following natural and experimental
      infection in pigs.
AB  - Clinical salmonellosis associated with Salmonella is increasingly reported in
      finishing swine. Since S. Typhimurium is often associated with these episodes and
      given that this serotype is among the most often reported in humans, we were
      interested to determine if various tissues and carcasses from animals coming from
      herds that were clinically affected were more likely to be contaminated by
      Salmonella compared to carcasses from animals raised in herds without any history
      of salmonellosis. Carcasses from animals from affected herds were significantly
      more contaminated by Salmonella while showing increased titers in antibodies
      directed against this bacterium. At the opposite, caecal contents and mesenteric
      lymph nodes from both groups of animals were similarly contaminated by
      Salmonella. In the second part of the study, we studied the persistence of the
      bacterium in various tissues after an experimental infection with S. Typhimurium.
      We found that, after the infection, Salmonella persisted for as many as 7 d in
      many extraintestinal tissues, while it was present in the feces of infected
      animals for all 14 d of the experiment. These findings indicated that carcasses
      from animals that experienced salmonellosis during their growth phase are more
      likely to be contaminated by this bacterium and that precautions must be taken in
      order to ensure that clinically affected animals should be kept on the farm for
      at least 7 d before being shipped for slaughter.

PMID- 15581218
TI  - Lactobacillus rhamnosus strain GG is a potential probiotic for calves.
AB  - Diarrhea is a common occurrence in neonatal calves. Several veterinary probiotics
      claiming to prevent or treat calf diarrhea are available, but have not been well
      studied. This study assessed the capability of Lactobacillus rhamnosus strain GG
      (LGG) to maintain viability in the gastrointestinal tract of calves. We also
      determined whether LGG can be administered in an oral rehydration solution (ORS)
      without compromising the efficacy of the ORS or the viability of LGG, and whether
      LGG produces D-lactate or not. To investigate the intestinal survival of LGG, 15
      calves were randomized into 3 groups and LGG was administered orally with their
      morning milk feeding on 3 consecutive days at a low (LD), medium (MD), or high
      (HD) dosage. Fecal samples were collected on days 0 (control), 1, 2, 3, 5, and 7
      and incubated for 72 h on deMan, Rogosa, Sharpe agar. Twenty-four hours after the
      1st feeding, LGG was recovered from 1 out of 5 calves in the LD group, 4 out of 5
      calves in the MD group, and 5 out of 5 calves in the HD group. To determine if
      LGG caused the glucose levels in the ORS to drop below effective levels, 1.5 L of
      the ORS was incubated with LGG for 2 h at 37 degrees C and the glucose
      concentration was measured every 20 min using a glucose meter. This ORS was then
      further incubated for 10 h and aliquots analyzed by high performance liquid
      chromatography to determine if D-lactate was produced by LGG. Glucose
      concentrations did not change over the 2 h of incubation, and no D-lactate was
      produced after 48 h. The LGG maintained viability in ORS. Therefore, this study
      demonstrated that LGG survives intestinal transit in the young calf, produces no
      D-lactate, and can be administered in an ORS.

PMID- 15581219
TI  - Comparison of commercial enzyme-linked immunosorbent assays and agar gel
      immunodiffusion tests for the serodiagnosis of equine infectious anemia.
AB  - The purpose of this study was to estimate the performance characteristics
      (accuracy, detection limit, and precision) of commercially available enzyme
      linked immunosorbent assay (ELISA) and agar gel immunodiffusion (AGID) kits in
      comparison with a reference AGID kit for the detection of equine infectious
      anemia (EIA) antibodies in horses for regulatory use in Canada. A total of 285
      positive and 315 negative samples by the reference AGID were tested blindly on 2
      other AGID and 4 ELISA kits. Commercially available AGID kits for the
      serodiagnosis of EIA were found equivalent. The 3 ELISAs directed against
      antibodies to the p26 core protein also performed relatively well in comparison
      with the reference AGID, with excellent relative accuracy and acceptable
      precision. The single ELISA directed against antibodies to the gp45 trans
      membrane viral protein yielded a lower relative sensitivity. The performance
      characteristics of the ELISAs directed against antibodies to p26 are, therefore,
      adequate to support the implementation of ELISA for regulatory purposes in
      Canada.

PMID- 15581220
TI  - Evaluation of the presence of porcine reproductive and respiratory syndrome virus
      in pig meat and experimental transmission following oral exposure.
AB  - A study was performed to evaluate the presence of porcine reproductive and
      respiratory syndrome virus (PRRSV) in pig meat collected at slaughterhouses and
      its potential transmission to pigs via pig meat. A total of 1039 blood samples
      were collected from pigs upon their arrival at the abattoir. The following day,
      meat samples (n = 1027) were collected from the carcasses of these same pigs.
      Samples originated from 2 Canadian slaughterhouses, 1 situated in the province of
      Quebec and the other situated in the province of Manitoba. Serum samples were
      tested for antibodies to PRRSV and both serum and meat samples were also tested
      for PRRSV nucleic acid by polymerase chain reaction (PCR). Seropositivity to
      PRRSV for all serum samples was 74.3%. Furthermore 45 (4.3%) of the total serum
      samples and 19 (1.9%) of the 1027 meat samples were positive for PRRSV by PCR.
      Sequence analysis of open reading frame (ORF) 5 performed on 15 of the 19 PRRSV
      strains identified in pig meat indicated that 9 were field strains and 6 were
      vaccine-like (98% to 99.7% nucleotide homology with the Ingelvac RespPRRS/Repro
      vaccine). One of these 6 strains presented an intermediate 2-6-2 restriction
      fragment length polymorphism (RFLP) cut pattern and the others showed the
      characteristic 2-5-2 RFLP pattern of the vaccine strain. All strains sequenced
      were determined to be North American strains. In only 1 of the 19 PRRSV-positive
      meat samples could PRRSV be isolated. To test the potential infectivity of meat
      samples containing residual PRRSV, 11 of the PCR-positive meat samples (weighing
      1.05 to 1.8 kg) were each used in feeding experiments of 2 PRRSV antibody
      negative specific pathogen-free pigs of 9 wk of age. Samples were cut into
      several pieces and fed to each pair of pigs on 2 consecutive days. Each pig pair
      was housed in a separate cubicle and serum samples were collected at -7, 0, 7,
      14, and 20 to 21 days post exposure. Seven pig pairs were found to be infected by
      PRRSV following ingestion of meat samples, including meat samples containing
      vaccine-like virus, as judged by the demonstration of PRRSV antibodies and/or
      PRRSV nucleic acid in the serum. In summary, the present study indicated that low
      residual quantities of PRRSV may be found in a small percentage of pig meat
      collected at slaugtherhouses. Furthermore, when this meat was fed raw to pigs in
      the experimental setting designed, pigs could be infected by PRRSV.

PMID- 15581222
TI  - Cardiopulmonary effects of romifidine/ketamine or xylazine/ketamine when used for
      short duration anesthesia in the horse.
AB  - The cardiovascular changes associated with anesthesia induced and maintained with
      romifidine/ketamine versus xylazine/ ketamine were compared using 6 horses in a
      cross over design. Anesthesia was induced and maintained with romifidine (100
      microg/kg, IV)/ketamine (2.0 mg/kg, IV) and ketamine (0.1 mg/kg/min, IV),
      respectively, in horses assigned to the romifidine/ ketamine group. Horses
      assigned to the xylazine/ketamine group had anesthesia induced and maintained
      with xylazine (1.0 mg/kg, IV)/ketamine (2.0 mg/kg, IV) and a combination of
      xylazine (0.05 mg/kg/min, IV) and ketamine (0.1 mg/kg/min, IV), respectively.
      Cardiopulmonary variables were measured at intervals up to 40 min after
      induction. All horses showed effective sedation following intravenous romifidine
      or xylazine and achieved recumbency after ketamine administration. There were no
      significant differences between groups in heart rate, arterial oxygen partial
      pressures, arterial carbon dioxide partial pressures, cardiac index, stroke
      index, oxygen delivery, oxygen utilization, systemic vascular resistance, left
      ventricular work, or any of the measured systemic arterial blood pressures.
      Cardiac index and left ventricular work fell significantly from baseline while
      systemic vascular resistance increased from baseline in both groups. The oxygen
      utilization ratio was higher in the xylazine group at 5 and 15 min after
      induction. In conclusion, the combination of romifidine/ketamine results in
      similar cardiopulmonary alterations as a xylazine/ketamine regime, and is a
      suitable alternative for clinical anesthesia of the horse from a cardiopulmonary
      viewpoint.

PMID- 15581221
TI  - Virological and immunological responses to porcine reproductive and respiratory
      syndrome virus in a large population of gilts.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes a prolonged
      active infection followed by a persistent infection in lymphoid tissues lasting
      for several months. Pigs develop both an antibody and cell-mediated immune
      response following PRRSV infection, but the specific role of each type in the
      development of protective immunity and clearance of the virus is not yet known.
      The aims of this study were to characterize the dynamics of PRRSV persistence
      from 0 to 135 d post infection (pi), characterize the kinetics of the antibody
      mediated immune response following PRRSV infection, and characterize the cell
      mediated immune responses to PRRSV infection. Eighty, 4-month-old PRRSV-free
      gilts were obtained from a source known to be negative for PRRSV. On day 0, gilts
      were infected intranasally with 10(2.4) TCID/50 MN 30-100 PRRSV. Following
      infection, animals were bled between days 0 to 135 pi. Viremia was detected up to
      day 30. Serum antibody response (by enzyme-linked immunosorbent assay [ELISA] and
      virus neutralization antibody) was detected from day 14 to 120 pi. Cell-mediated
      immune response represented by interferon gamma (IFN-gamma) was detected from day
      14 to 120 pi. Persistence of PRRSV in tissues was confirmed by reverse
      transcriptase polymerase chain reaction (RT-PCR) between days 30 to 135. These
      results indicate that serum neutralizing antibodies and IFN-gamma play an
      important role in the clearance of PRRSV. Nevertheless none of the parameters
      measured (virus neutralizing antibodies), either alone or in combination, are
      solely responsible for the clearance of the virus from the host and the
      development of sterilizing immunity.

PMID- 15581223
TI  - Luteolysis, onset of estrus, and ovulation in Holstein heifers given
      prostaglandin F2alpha concurrent with, or 24 hours prior to, removal of an
      intravaginal, progesterone-releasing device.
AB  - The objective was to determine the effects of giving prostaglandin F2alpha (PGF)
      concurrent with, or 24 h before, removal of an intravaginal, progesterone
      releasing (controlled internal drug release [CIDR]) device, on luteolysis, the
      synchrony of estrus and ovulation. Eighteen postpubertal Holstein heifers were
      given a CIDR and 100 microg gonadotropin releasing hormone (GnRH) and equally
      allocated to 3 groups. The PGF was given concurrently with CIDR removal after 7
      or 8 d (groups D7/D7 and D8/D8, respectively) or given 1-d before removal of CIDR
      after 8 d (group D7/D8). There was no difference (P > 0.75) among groups in the
      intervals (h) from CIDR removal to onset of standing estrus and to ovulation
      (49.3 h+/-6.2 h and 77.5 h+/-9.0 h, respectively; least squares means+/-standard
      error of means). We also determined if stage of the estrus cycle influenced the
      synchrony of estrus or ovulation. In heifers in metestrus at CIDR insertion
      (versus those at estrus or diestrus), intervals from CIDR removal to estrus and
      to ovulation were longer by 33.4 h (P < 0.05) and 38.5 h (P = 0.01),
      respectively. However, the interval from standing estrus to ovulation was not
      affected. Giving PGF concurrent with CIDR removal did not affect luteal
      regression, the synchrony of estrus, and ovulation; but heifers in metestrus at
      the initiation of treatment had longer intervals from CIDR removal to estrus and
      ovulation.

PMID- 15581224
TI  - Evaluation of cutaneous analgesia after non-focused extracorporeal shock wave
      application over the 3rd metacarpal bone in horses.
AB  - Extracorporeal shock wave therapy is becoming increasingly used in equine
      practice to treat musculoskeletal disorders. Although the exact effects of
      extracorporeal shock waves on tissues still need to be elucidated, transient
      cutaneous analgesia has been observed within treated areas in humans and horses.
      The purpose of this study was to determine the onset, magnitude, and duration of
      cutaneous analgesia after non-focused extracorporeal shock wave (ESW) application
      by comparing the limb withdrawal reflex latency (LWRL) in treated and untreated
      areas on the metacarpus of horses, using a focused light source. A single
      treatment with non-focused ESW was applied to 3 areas over the dorsal aspect of
      one metacarpus in 12 horses. The LWRL was measured to assess cutaneous sensation
      in treated and untreated control areas of the treated metacarpus and in an
      untreated area on the opposite metacarpus, before and at various time points
      after ESW application. Most treated and control areas revealed a significant
      decrease in LWRL over time compared with baseline values. Although the results of
      our study do not suggest cutaneous analgesia after ESW application to the equine
      metacarpus, we advise cautious use of this treatment modality for horses in
      training or before competition until further research is done.

PMID- 15581225
TI  - Cloning and characterization of a bovine genomic fragment homologous to epidermal
      growth factor genes.
AB  - Epidermal growth factor (EGF) is a potent mitogen for a variety of cell types.
      The 53-amino acid mature EGF protein is encoded by sequences in exons 20 and 21
      of a gene spanning over 110 kb. In this study, we report the cloning and
      characterization of 7.5 kb of bovine genomic sequence homologous to exon 19
      through 21 from EGF genes from other mammalian species. The cloned gene fragment
      had an unusual sequence composition in the form of an in-frame TGA codon in the
      coding sequence. The sequence was expressed at low levels in kidney tissue and
      the corresponding cDNA contained the TGA codon. The level of similarity between
      the bovine exonic sequence and the human, porcine, murine, feline, and canine
      corresponding sequences varied from 64% to 73%; however, when only sequences
      encoding the mature EGF protein were compared, the level of similarity between
      the bovine sequence and the sequence from these species was 59% to 66%. The
      sequence similarity of the deduced mature protein was lower (34% to 39%) than the
      sequence similarity of the deduced propeptide. Although the cloned sequences
      could originate from a bovine EGF pseudogene, the possibility exists that they
      originate from the functional EGF gene. An as yet unidentified mechanism to by
      pass the stop codon would allow the synthesis of a functional EGF protein.
      Alternatively, the cloned sequence could originate from an EGF-like gene.

PMID- 15581226
TI  - Immunological response to Mycobacterium avium subsp. paratuberculosis in
      chickens.
AB  - Enzyme-linked immunosorbent assay (ELISA) and culture are 2 common diagnostic
      tests for detecting Mycobacterium avium subsp. paratuberculosis (Map) in Johne's
      disease, but they are not as sensitive as polymerase chain reaction (PCR).
      However, inhibitors can coextract with the target DNA and cause interference in
      PCR. Development of an immune capture assay followed by PCR amplification can
      alleviate this problem. In this study, we were able to induce an immune response
      in chickens using heat or formalin inactivated Map. The purified immunoglobulin
      (Ig)Y has a molecular weight of 160 kDa. The titers were at 1:6400 and 1:12 800
      at weeks 5 to 6 and 8 to 9, respectively, as determined by the IDEXX modified
      ELISA kit for Johne's disease. The IgY produced from inactivated bacterial cells
      had no effect on its ability to recognize live Map cells as illustrated by
      immunofluorescence assay and immune capture PCR results.

PMID- 15581227
TI  - Development and analytical validation of a radioimmunoassay for the measurement
      of feline pancreatic lipase immunoreactivity in serum.
AB  - Pancreatitis is recognized as an important cause for morbidity and mortality in
      cats, but diagnosis remains difficult in many cases. As a first step in trying to
      identify a better diagnostic tool for feline pancreatitis the objective of this
      project was to develop and analytically validate a radioimmunoassay for the
      measurement of feline pancreatic lipase immunoreactivity (fPLI). Feline
      pancreatic lipase (fPL) was purified from pancreatic tissue and antiserum against
      fPL was raised in rabbits. Tracer was produced by iodination of fPL using the
      chloramine T method. A radioimmunoassay was established and analytically
      validated by determination of sensitivity, dilutional parallelism, spiking
      recovery, intra-assay variability, and interassay variability. A control range
      for fPLI in cat serum was established from 30 healthy cats using the central 95th
      percentile. The sensitivity of the assay was 1.2 microg/L. Observed to expected
      ratios for serial dilutions ranged from 98.8% to 164.3% for 3 different serum
      samples. Observed to expected ratios for spiking recovery ranged from 76.9% to
      147.6% for 3 different serum samples. Coefficients of variation for intra- and
      interassay variability for 4 different serum samples were 10.1%, 4.5%, 2.2%, and
      3.9% and 24.4%, 15.8%, 16.6%, and 21.3%, respectively. A reference range for fPLI
      was established as 1.2 to 3.8 microg/L. We conclude that the assay described is
      sensitive, accurate, and precise with limited linearity in the lower and limited
      reproducibility in the lower and higher end of the working range. Further studies
      to evaluate the clinical usefulness of this assay are needed and in progress.

PMID- 15581229
TI  - Accurate referential communication and its relation with private and social
      speech in a naturalistic context.
AB  - Research into human communication has been grouped under two traditions:
      referential and sociolinguistic. The study of a communication behavior
      simultaneously from both paradigms appears to be absent. Basically, this paper
      analyzes the use of private and social speech, through both a referential task
      (Word Pairs) and a naturalistic dyadic setting (Lego-set) administered to a
      sample of 64 children from grades 3 and 5. All children, of 8 and 10 years of
      age, used speech that was not adapted to the decoder, and thus ineffective for
      interpersonal communication, in both referential and sociolinguistic
      communication. Pairs of high-skill referential encoders used significantly more
      task-relevant social speech, that is, cognitively more complex, than did low
      skill dyads in the naturalistic context. High-skill referential encoder dyads
      showed a trend to produce more inaudible private speech than did low-skill ones
      during spontaneous communication. Gender did not affect the results.

PMID- 15581228
TI  - Evaluation of the cationic trypsinogen gene for potential mutations in miniature
      schnauzers with pancreatitis.
AB  - The purpose of this study was to evaluate the cationic trypsinogen gene in
      miniature schnauzers for possible mutations. Genetic mutations have been linked
      with hereditary pancreatitis in humans. Four miniature schnauzers were selected
      on the basis of a clinical history of pancreatitis. One healthy miniature
      schnauzer and 1 healthy mixed breed canine were enrolled as controls. DNA was
      extracted from these canines using a commercial kit. Primers were designed to
      amplify the entire canine cationic trypsinogen cDNA sequence. A polymerase chain
      reaction (PCR) was performed and products were purified and sequenced. All
      sequences were then compared. The healthy control canine, a healthy miniature
      schnauzer, and the 4 miniature schnauzers with pancreatitis showed identical
      sequences of the cationic trypsinogen gene to the published sequence. We conclude
      that, in contrast to humans with hereditary pancreatitis, mutations of the
      cationic trypsinogen gene do not play a major role in the genesis of pancreatitis
      in the miniature schnauzer.

PMID- 15581230
TI  - Composite and preferences Scales of Morningness: reliability and factor
      invariance in adult and university samples.
AB  - The creation and adaptation of scales or inventories assessing specific circadian
      typologies has been a predominant focus within the field of chronopsychology. The
      present study addressed the psychometric properties of two scales of morningness
      eveningness: the Morningness Composite Scale (CS; Smith, Reilly, & Midkiff, 1989)
      and the Early/Late Preferences Scale (PS; Smith, Folkard, Schmieder, Parra,
      Spelten, & Almirall, 1993). Internal consistency and factor invariance of the CS
      and PS were analyzed in two samples: a group of 203 university students (age
      range = 19-30) and a group of 125 working adults (age range = 31-65). Results
      indicated satisfactory internal consistency for both full scales with each age
      group and confirmed the factor invariance across age for the two CS factors and
      one of the PS factors. A higher tendency in morningness on both scales was noted
      in the adult sample.

PMID- 15581231
TI  - On a practitioner's need of further development of Wechsler scales. Adaptive
      Intelligence Diagnosticum (AID 2).
AB  - Wechsler's intelligence test-batteries are still popular yet suffer from
      psychometric shortcomings and lack a certain content improvement and enlargement.
      In this paper a new approach will be presented that suits traditional Wechsler
      testing. The approach in question is the Adaptive Intelligence Diagnosticum (AID
      2; Kubinger & Wurst, 2000). Due to it's "branched testing" design, AID 2 works
      out to be more economical and in this regard also offers other advantages, such
      as parallel tests and short forms. AID 2 offers a method of survey for
      identifying specific developmental disorders or learning disabilities. It
      includes an optional non-verbal instruction and a schedule for retrograde
      observation support of behavioral misfits. It also offers discriminative
      indicators for intellectual neglect vs. intellectual advancement.

PMID- 15581232
TI  - Accuracy in discriminating blood glucose levels in a sample of children with type
      1 diabetes.
AB  - The present study explores accuracy in estimating blood glucose levels (BGL) in
      children with type 1 diabetes and analyzes the kinds of symptoms and cues which
      they use to estimate their BGL. Forty two children with type 1 diabetes completed
      a SI/IC-3 scale consisting of 28 items (22 symptoms and 6 feelings), indicating
      those which they perceived at the time and their intensity. They estimated their
      BGL and gave reasons for their estimation, before having a blood glucose level
      analysis performed. The results indicated great variability in the accuracy of
      estimating BGL. They showed failures in the correct discrimination of symptoms of
      hypoglycemia as well as the presence of false beliefs regarding indicative
      symptoms of hyperglycemia, and the absence of symptoms as an indicator for
      euglycemia, beliefs which provoke different and frequent errors in the estimation
      of BGL. Correct use of external signs is shown to be related to correct
      estimations of normal BGL, as well as hypoglycemia and hyperglycemia. We discuss
      the implications these results could have on designing psychological intervention
      procedures for diabetics in the form of training programs to discriminate BGL
      accurately, taking into account these findings and previous studies completed in
      the same field.

PMID- 15581233
TI  - Collectivize social support? Elements for reconsidering the social dimension in
      the study of social support.
AB  - Psychological models of mental disorders play an important role in the
      explanation of psychological deterioration. Researchers from this area usually
      study several cognitive and behavioral variables to account for the onset and
      maintenance of depression. However, many authors have detected the need to
      include a "social dimension" in the explanation of deterioration. In this sense,
      social support has become a crucial aspect in the study of mental health, and the
      psychological literature on this topic has generated an intense debate about
      several facets of the positive impact of social networks on psychological well
      being. In this article, the author defends that this increasing centrality of the
      concept has been accompanied by a psychological reductionism that is making the
      role of "social aspects" to explain psychological well-being more problematic.
      Implications of this reductionism are discussed, and an alternative proposal is
      made to overcome some theoretical and empirical problems related to social
      support research.

PMID- 15581234
TI  - A daughter's retrospective of B. F. Skinner.
AB  - This paper describes characteristic behaviors of my father, B. F. Skinner, using
      family documents and my own recollections. Early contingencies in his upbringing
      strengthened his love of building things and his independence in discovering how
      the world works. Those skills, combined with a lack of supervision in graduate
      school, set the stage for his discovery of the operant. He did not stop with
      laboratory research. He extended his discovery of how consequences select
      behavior into education and the design of cultural practices. As well as solving
      society's problems, my father was always concerned with improving his own
      behavior. Some of the contingencies he set up to maximize his own productivity
      are described.

PMID- 15581235
TI  - The triad of science foundations, instructional technology, and organizational
      structure.
AB  - Over the centuries and across all societies educational achievement does not
      improve. The attempt to improve the instructional process has concentrated on
      instructional technology. But these attempts have overlooked the importance of
      two other factors: the science that should underlie the instructional
      technologies and the organization that must operate those technologies. A
      considerable step forward in handling the problems of instructional effectiveness
      has been the derivation of instructional technologies based on Skinnerian
      science. But the instructional technologies based on Skinner's analysis of
      behavior are promoted as if they were to operate in an organizational vacuum. The
      division of labor, and its necessary coordination and control, is taken for
      granted. But in any large scale enterprise, the organization of the division of
      labor must fit the technology through which that enterprise achieves its mission.
      Educational technology must tie directly to a pertinent science and to a proper
      organizational structure. To teach effectively requires an overhaul along three
      lines: 1) a relevant science that reflects and encapsulates an accurate
      understanding of behavior; 2) a contingency-based technology of instruction that
      directly derives its practices upon proper scientific principles; and 3) a
      suitable organization based on teaching teams that operate the new instructional
      technology.

PMID- 15581236
TI  - A note on Skinner and Pavlov's physiology.
AB  - These short notes describe the way in which Skinner considers and resolves his
      differences with Pavlov in the question of the relation between psychology and
      physiology as forms of knowledge. After establishing his viewpoint in the general
      epistemological issue, Skinner is concerned about linking his study of behavior
      to the work of Pavlov, who considered it to be of a physiological nature. Skinner
      contrasts Pavlov's empirical and theoretical work and characterizes the latter in
      terms of the notion of the "Conceptual Nervous System."

PMID- 15581237
TI  - Acquisition, learning, or development of language? Skinner's "Verbal Behavior"
      revisited.
AB  - In 1957, Skinner, in his "Verbal Behavior", proposed an explanation on how a
      language is learned. In 1959, Chomsky strongly argued the non-learnability of
      language, establishing in the field of developmental psycholinguistics the
      substitution of the term "learning" for that of "acquisition". Currently, the
      constructivist models describe language acquisition as a process of ontogenetic,
      gradual, complex, and adaptive change. This new theoretical framework has been
      especially useful for rereading Verbal Behavior because it facilitates recovering
      the Skinnerian learning mechanisms. This can be observed in the recent research
      trends that recapture reinforcement and imitation (echoic responses), although
      they are now located in the initial phases of the process and are included in a
      cognitive dynamic that, by gradually increasing its complexity, can achieve
      grammar. The new constructivist theoretical framework, by retrieving the
      functional and referential aspects of language, can also take advantage of the
      classic Skinnerian proposal about the pragmatic types of verbal behavior,
      providing it with new meaning.

PMID- 15581238
TI  - Psychopathology according to behaviorism: a radical restatement.
AB  - This article is a radical restatement of the predominant psychopathology, which
      is characterized by nosological systems and by its approach towards a
      neurobiological conception of the so-called mental disorders. The "radical" sense
      of this restatement is that of radical behaviorism itself. As readers will
      recall, "radical" applied to behaviorism means total (not ignoring anything that
      interests psychology), pragmatic (referring to the practical sense of knowledge),
      and it also derives from the Latin word for "root" (and thus implies change
      beginning at a system's roots or getting to the root of things, in this case, of
      psychological disorders). Based on this, I introduce the Aristotelian distinction
      of material and form, which, besides being behaviorist avant la lettre, is used
      here as a critical instrument to unmask the hoax of psychopathology as it is
      presented. The implications of this restatement are discussed, some of them
      already prepared for clinical practice.

PMID- 15581239
TI  - Skinner and the rise of behavior modification and behavior therapy.
AB  - Skinner is, without a doubt, one of the most predominant figures in the
      development of Behavior Modification and Behavior Therapy. Skinners' work is
      essential to the development of Behavior Modification and Behavior Therapy.
      Beginning with the social need for efficient psychotherapy, and after having
      generated a solid theoretical body of behavioral laws, Skinner indicated and also
      developed the appropriate path towards efficient interventions for unadaptive
      behavior. He developed a new theory regarding abnormal behavior
      (psychopathology), as well as a procedural model for evaluation (diagnosis) and
      intervention: "The functional analysis of behavior". His applications for this
      kind of work are pioneering and at the same time, he is the agglutinant figure of
      what we today call "Behavior Modification and/or Therapy". It is remarkable that
      a scientist could change the theories and practices of a discipline as radically
      as Skinner and his work did. His work, however, still has its limitations. The
      best way to acknowledge and pay tribute to Skinners' work is to overcome these
      limitations.

PMID- 15581240
TI  - A few simple rules for managing block time in the operating room.

PMID- 15581241
TI  - AARP shares winning policies for keeping mature employees.

PMID- 15581242
TI  - California alert follows scope lapses.

PMID- 15581243
TI  - A consensus on improving antibiotic use.

PMID- 15581244
TI  - What's the best way to adjust block time?

PMID- 15581245
TI  - OR's policies friendly to a senior staff.

PMID- 15581246
TI  - Supply cabinets: an open or closed case?

PMID- 15581247
TI  - Options for smaller ORs.

PMID- 15581248
TI  - Volunteers pitch in to help educate perioperative staff.

PMID- 15581249
TI  - Will staff be ready for no-knock surveys?

PMID- 15581250
TI  - How did the new tracer process go?

PMID- 15581251
TI  - New clues on how to inactivate prions.

PMID- 15581252
TI  - Benchmark data drives QI projects.

PMID- 15581253
TI  - Meeting JCAHO's goal on surgical fires.

PMID- 15581254
TI  - Pharmacists aid in disease management for American Indians, Alaska Natives.

PMID- 15581255
TI  - Higher spending, more care do not lead to better outcomes, studies say.

PMID- 15581256
TI  - Medicare readies chronic care initiative.

PMID- 15581257
TI  - National Cancer Institute cranks up nanotechnology research.

PMID- 15581258
TI  - Pharmacist interventions in an anticoagulation clinic.

PMID- 15581259
TI  - Monitoring for potential adverse drug reactions in patients receiving
      chemotherapy.

PMID- 15581260
TI  - Drug-resistant pneumococci: what can pharmacists do about it?

PMID- 15581261
TI  - Pharmacotherapy, pharmacogenomics, and the future of alcohol dependence
      treatment, Part 2.
AB  - PURPOSE: The neurobiological basis of alcohol dependence, established
      pharmacotherapies for alcohol dependence, pharmacotherapies under investigation,
      and obstacles to treatment are discussed. SUMMARY: Alcohol binds to hydrophobic
      pockets of proteins, changing their three-dimensional structure and their
      function. Proteins that are particularly sensitive to alcohol include ion
      channels, neurotransmitter receptors, and enzymes involved in signal
      transduction. Established pharmacologic treatments, notably disulfiram and
      naltrexone, combined with behavioral therapies, may reduce the amount of
      drinking, the risk of relapse, the number of days of drinking, and craving in
      some alcohol-dependent individuals. For many patients, however, these treatments
      are not effective. Recent advances in molecular and behavior genetics are guiding
      the development of new drugs; these efforts seek to identify pharmacologic
      pathways relevant to alcohol dependence and to more effectively match treatments
      to individuals according to their genetic characteristics. Efficacy and safety
      concerns for acamprosate have been satisfied; the drug was recently released for
      marketing in the United States. Medications such as sertraline, ondansetron,
      topiramate, and aripiprazole represent novel lines of research and are currently
      being tested for use in the treatment of alcoholism. Even with more efficacious
      medications, however, a transformation must occur in how alcoholism treatment is
      viewed, not only by the public but also by clinicians. CONCLUSION: In addition to
      existing drug treatments for alcohol dependence, many other medications are under
      investigation, particularly for specific types of alcoholism. Pharmacogenomics is
      expected to play an important role in this research effort.

PMID- 15581262
TI  - Atomoxetine: the first nonstimulant for the management of attention
      deficit/hyperactivity disorder.
AB  - PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, drug
      interactions, dosage and administration, and place in therapy of atomoxetine in
      the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed.
      SUMMARY: Atomoxetine is a methylphenoxy-benzenepropanamine derivative with
      antidepressant activity and is thought to enhance noradrenergic function via
      selective inhibition of the presynaptic norepinephrine transporter. Atomoxetine
      is rapidly absorbed from the gastrointestinal tract, reaching peak levels in 1.83
      hours in pediatric patients and 1-1.5 hours in adults. The clinical efficacy of
      atomoxetine in the treatment of ADHD has been evaluated in six published clinical
      trials of children and adolescents and two studies enrolling only adults.
      Clinical trial data indicate that atomoxetine is safe and well tolerated for the
      treatment of ADHD; however, safety data about long-term use (greater than one
      year) are unavailable. Adverse events reported in clinical trials were mainly
      mild to moderate and transient in nature. Recommended dosing of atomoxetine is
      weight based, and dosages should be adjusted to a target dosage of 1.2 mg/kg/day
      in children and adolescents weighing 70 kg or less and to 80 mg/day in children
      and adolescents weighing over 70 kg and adults. While current guidelines from the
      American Academy of Pediatrics recommend stimulants and behavior modification as
      first-line therapy for the management of ADHD, atomoxetine offers those patients
      who do not respond to or cannot tolerate one or more stimulants an alternative
      treatment option. CONCLUSION: Atomoxetine, the first non-stimulant approved for
      the management of ADHD in children, adolescents, and adults, provides patients
      who have not responded to or cannot tolerate one or more stimulants an
      alternative treatment option.

PMID- 15581263
TI  - Association between self-monitoring of blood glucose and glycemic control in
      patients with type 2 diabetes mellitus.
AB  - PURPOSE: The relationship between the self-monitoring of blood glucose (SMBG) and
      glycemic control in patients with type 2 diabetes mellitus in a Veterans Affairs
      (VA) medical center was studied. METHODS: Laboratory, inpatient, outpatient, and
      demographic data for patients with type 2 diabetes mellitus who were seen for
      three years continuously or receiving their care regularly from a single Texas VA
      facility between October 1, 1999, and September 30, 2002, were obtained. Local
      pharmacy data were used to identify patients who received blood-glucosemonitoring
      strips. Patients were assigned to one of four mutually exclusive groups: those
      who did not receive monitoring strips at all, those who received strips in fiscal
      year (FY) 2002 only, those who received strips in FYs 2001 and 2002, and those
      who received strips during all three years (FYs 2000, 2001, and 2002). Frequency
      of monitoring and case-mix scores were measured. Nonparametric statistics were
      used to compare the demographic and clinical characteristics of the four groups.
      Robust regression was used to analyze the relationships between SMBG and glycemic
      control in FY 2002. RESULTS: Of the 1185 patients who received oral hypoglycemic
      medications during all three fiscal years, 976 patients met the criteria for
      inclusion in one of the four groups. There were no significant differences among
      the four groups in baseline hemoglobin A1c (HbA1c) values, body mass index, or
      case-mix scores. The Kruskal-Wallis test found no significant difference among
      the four groups in the number of laboratory blood glucose tests conducted, but
      there were significant differences in the number of HbA1c tests conducted among
      the groups. CONCLUSION: SMBG was not associated with glycemic control in VA
      patients with type 2 diabetes mellitus managed on oral hypoglycemic medications.

PMID- 15581264
TI  - Effect of quercetin on the pharmacokinetics of oral cyclosporine.

PMID- 15581265
TI  - Intervention for decreasing excessive acetaminophen use in Pennsylvania Medicaid
      recipients.

PMID- 15581266
TI  - Compatibility of argatroban with selected cardiovascular agents.

PMID- 15581267
TI  - Implementing computerized prescriber order entry in a children's hospital.

PMID- 15581268
TI  - ASHP therapeutic position statement on strategies for identifying and preventing
      pneumococcal resistance.
AB  - The incidence of drug-resistant S. pneumoniae continues to increase, causing
      significant morbidity and mortality. Health care providers should seize the
      opportunity to promote the judicious use of antimicrobials and aggressive
      vaccination with the pneumococcal vaccines as a means to lessen this significant
      health problem.

PMID- 15581269
TI  - Effects of prenatal hydroxyurea-treatment on mouse offspring.
AB  - Hydroxyurea (HU), a ribonucleotide reductase inhibitor, induces morphological
      anomalies in the central nervous system, craniofacial tissues and limb buds in
      animals, and neonatal respiratory distress in humans. The neonates and offspring
      of pregnant mice treated with 400 or 800 mg/kg of HU on day 13 of gestation were
      examined at 0 day and 10 weeks after birth to find a clue for clarifying the
      relationship between HU-induced apoptosis in the fetal tissues and
      teratogenicity. The offspring from dams treated with HU were retarded in growth
      compared with controls. But there was no significant difference in the body
      weight gain between the 400 and 800mg/kg groups. In the teratologic changes,
      microencephaly, hydrocephalus and curved coccygeal vertebrae were observed in the
      offspring, and the incidence of these teratologic changes was similar but their
      degree was more severe in the 800 mg/kg group than in the 400 mg/kg group. Based
      on the above-mentioned previous and present studies of ours, we suggest that HU
      induced apoptosis in fetal tissues may play an important role in the development
      of anomalies in the corresponding tissues of offspring.

PMID- 15581270
TI  - Spontaneous epithelial plaques in the uterus of a non-pregnant cynomolgus monkey
      (Macaca fascicularis).
AB  - Two epithelial plaques were observed in the uterus of a 4 years 8 month old non
      pregnant cynomolgus monkey. Normally, epithelial plaques occur near the
      implantation site of primates during early pregnancy but can also be induced by
      various procedures. Both plaques consisted of clusters and nest of cells with
      large nuclei and a faintly basophilic cytoplasm. Marked cellular pleomorphism was
      seen, including cells with giant nuclei and binucleated cells. Further
      histological features were vacuolation, mitosis and PAS-positive granules in
      several cells and polymorphonuclear infiltration in the periphery of the plaque.
      This is the second description of a spontaneous epithelial plaque in a primate
      and the first in a cynomolgus monkey.

PMID- 15581271
TI  - Effects of lipopolysaccharide on the appearance of macrophage populations and
      fibrogenesis in cisplatin-induced rat renal injury.
AB  - Macrophages play an important role in renal interstitial fibrosis via production
      of transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha
      (TNF-alpha); these fibrogenic factors mediate induction of myofibroblastic cells
      capable of producing extracellular matrices. We investigated the effects of
      lipopolysaccharide (LPS), a macrophage activator, on the appearance of macrophage
      populations and subsequent fibrogenesis in cisplatin (CDDP)-induced rat renal
      lesions. In keeping with the progression of interstitial fibrosis, alpha-smooth
      muscle actin (alpha-SMA)-immunopositive myofibroblastic cell number began to
      increase on day 4 and continued gradually until day 16 after CDDP injection.
      Cells immunoreactive for ED1 (for exudate macrophages), ED2 (for resident
      macrophages) and ED3 (for activated resident macrophages) showed the highest
      number on day 4 or day 7, and thereafter, the numbers were gradually decreased up
      to day 16. On the other hand, the number of cells immunoreactive for OX6 (rat MHC
      class II-recognizing antibody) was increased on day 7 and remained elevated up to
      day 16. LPS was injected on day 7 after CDDP injection when the greatest number
      of ED1-positive macrophages were present. In CDDP/LPS-injected rats, the numbers
      of macrophages reacting to ED1, ED2, ED3, and OX6 were higher than those in CDDP
      injected rats during the observation period between days 7 and 16; ED3- and OX6
      positive cells were more prominently increased than ED1- and ED2-postive cells.
      By RT-PCR analysis, the expression of TGF-beta1 and TNF-alpha mRNAs in CDDP/LPS
      injected rats on day 7 was markedly increased in contrast to those in CDDP
      injected rats. These findings indicate that LPS treatment enhanced the macrophage
      expression of fibrogenic factors. However, there was no marked difference in the
      fibrogenesis between CDDP/LPS- and CDDP-injected rats. These findings suggest
      that the macrophage populations appearing in CDDP-induced rat renal lesions
      should be investigated further, to address the complicated pathogenesis of renal
      interstitial fibrosis.

PMID- 15581272
TI  - Primary and transplanted ENU induced rat tumors in neurooncology.
AB  - In neurooncology transplanting, tumors can be used for many purposes e.g. to
      solve questions concerning the etiology and pathogenesis of such tumors or their
      management. Experimentally induced and transplanted tumors of the nervous system
      become reproducible in their morphology and growth parameters after about 12
      subsequent intracerebral passages. During the period from the first to the 12th
      intracerebral generations, a simplification of the histology and a reduction of
      the induction times take place. Nowadays the growth behavior of such tumors can
      be followed by imaging methods such as MRI if specially adapted to small animals.
      Our results are based on the investigation of over 2350 experimentally induced
      tumors of the central and peripheral nervous system that were diagnosed according
      to the rules of human and rodent brain tumor classification and various subgroups
      of this sample, analyzed by electron microscopy, postmortal angiography and MRI.

PMID- 15581273
TI  - Clinical and histopathological progression of lesions in lupus-prone (NZB x NZW)
      F1 mice.
AB  - This study was conducted to review the progression with age of renal and other
      changes in (NZB x NZW) F1 females obtained from a commercial colony, housed under
      SPF conditions. Sixty-two mice were given food and water ad libitum and
      sacrificed at intervals up to 47 weeks of age. Routine haematology and urinalysis
      were performed at regular intervals. The serum levels of IgA, IgG, IgM and
      antinuclear antibody levels were monitored along with urinary protein. Major
      organs and tissues from all animals were preserved and examined. Special
      attention was paid to the kidneys: in addition to routine 4-microm paraffin
      sections, 1-microm resin sections were prepared and examined. Positive levels of
      urinary protein (> 1 g/L) were only found in 50% of the animals, even at 32 weeks
      of age. Histopathologically, the expected type of glomerular damage was present;
      but the incidence and severity of the change were low, with only 33% of the mice
      affected at 32 weeks of age. Most mice had fatty vacuolation in the liver. At 24
      weeks of age, 50% of the mice sacrificed had haemorrhagic degeneration of the
      liver. This was not seen at later time points. Only two mice survived until 47
      weeks of age. In summary, these findings were of the expected type, but at a much
      lower incidence and severity than formerly reported. The background of the strain
      and the experimental conditions are of great importance in the progress of these
      renal lesions. The lack of homogeneity of the renal changes would make it
      difficult to determine any influence of xenobiotics on the progress of autoimmune
      diseases.

PMID- 15581274
TI  - L-cysteine-induced brain damage in adult rats.
AB  - The time-dependent brain damage induced in adult rats by a single dose of L
      cysteine was examined morphologically. Five-week-old male Sprague-Dawley rats
      that received 1500 mg/kg of L-cysteine by intraperitoneal injection were examined
      at 12 and 24 h and 3, 7, and 14 days after administration. Pathological changes
      were seen in the cerebral and cerebellar cortex. Neuronal karyopyknosis was
      observed in the granular and molecular layers of the superficial cerebellar
      cortex at 12 h, and well-demarcated infarct-like lesions were seen with a
      widespread distribution in the cerebral cortex at 24 h. A large number of lipid
      phagocytes and glial cell proliferation were noted in the affected regions on
      days 3 to 14. The neuronal cell death observed in the cerebellar granular layer
      cells was demonstrated to be due to apoptosis by histopathological and
      ultrastructural examinations as well as by the terminal deoxyribonucleotide
      transferase-mediated dUTP nick-end labeling (TUNEL) method and agarose gel
      electrophoresis for DNA laddering. It was found that L-cysteine induced brain
      lesions mainly in the cerebral and cerebellar cortex in adult rats, in contrast
      to lesions in various regions as observed in neonatal rats. The histopathological
      findings reported here suggest that the pathogenesis of the brain damage induced
      by L-cysteine in adult rats differs from that in neonatal rats. It appears likely
      that L-cysteine-induced brain damage is secondary to impairment of blood flow or
      other unknown factors that are responsible for the subsequent development of
      brain lesions.

PMID- 15581275
TI  - Morphology of experimentally induced tumors of the sympathetic nervous system in
      rats.
AB  - Seventeen tumors of the sympathetic nervous system were discovered in offspring
      of rats exposed in utero at a single dose of 80mg/kg of N-nitrosoethylurea at the
      day 16-19 of pregnancy, and then to constant light regimen. These tumors were
      classified as follows: benign--ganglioneuroma (six cases) and malignant-
      ganglioneuroblastoma (four cases) and neuroblastoma (seven cases). The most
      frequent location was in the sympathetic trunk in the mediastinum and in the
      retroperitoneal space. Morphological features of these induced tumors represent a
      model for similar neoplasms in humans in childrens' age.

PMID- 15581276
TI  - Effects of selenium on histopathological and enzymatic changes in experimental
      liver injury of rats.
AB  - The most important antioxidant aspect of selenium is its function in the active
      site of selenoenzyme glutathione peroxidase. Glutathione peroxidase not only
      allows the removal of the toxic radicals but also permits the regeneration of
      lipid molecules through reacylation in the cellular membrane. Thus, GSHPx may
      prevent the harmful effects of free radicals and may reduce the formation of the
      reactive metabolites of carbon tetrachloride. Carbon tetrachloride is a
      hepatotoxic agent which generates haloalkane radicals during its
      biotransformation in the liver and is widely used to make the experimental model
      of hepatic damage. Therefore, the aim of the present study is to investigate the
      possible protective role of selenium on the experimental liver cirrhosis and some
      enzyme activities in blood plasma from rats. While the activities of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase
      (ALP) were significantly increased (p < 0.05, p < 0.05 and p < 0.01,
      respectively), gamma-glutamyle transferase (GGT) activity was not statistically
      affected (p < 0.05) with carbon tetrachloride-injection. The levels of AST, ALT
      and GGT in carbon tetrachloride-group decreased to nearly the enzyme values in
      control-group after the selenium-injection but the ALP was increased (p<0.01). On
      the other hand, it was noticed that selenium significantly decreased the hepatic
      injury. In conclusion, our results showed that carbon tetrachloride caused an
      increase in the activities of liver enzymes in plasma and selenium application
      decreased the hepatic injury. Plasma levels of the liver enzymes were decreased
      after selenium-injections. Based upon these results, selenium may play an
      important role in the preventive indication of hepatic cellular injury inducted
      by carbon tetrachloride.

PMID- 15581277
TI  - Pathophysiology of traumatic injury in the developing brain: an introduction and
      short update.
AB  - Current understanding about the main peculiarities in pathophysiology of immature
      brain traumatic injury involves marked developmental discrepancy of biomechanical
      properties, aspects of altered features in water and electrolyte homeostasis as
      well as maturation dependent differences in structural and functional responses
      of major transmitter systems. Based on the fact that traumatic brain injury (TBI)
      is one of the major causes of morbidity and mortality in infants and children,
      the currently available epidemiological data are reviewed in order to gain
      insights about scope and dimension of health care engagement and derive the
      requirements for reinforced pathogenetic research. To this end, the main aspects
      of peculiarities in primary and secondary TBI mechanisms in the
      immature/developing brain are discussed, including structural and functional
      conditions resulting in a markedly diminished shear resistance of the immature
      brain tissue. As such, the immature brain tissue appears to be more susceptible
      to mechanical alterations, because similar mechanical load induces a more intense
      brain tissue displacement. Furthermore, available indications for increased
      incidence of brain swelling in the immature brain after TBI are reviewed,
      focusing on the interrelationship between the age-dependent differences in
      extracellular space and aquaporin-4 expression during brain maturation. The
      developmental differences of TBI induced cerebrovascular response as well as some
      relevant aspects of altered neurotransmission following TBI of the immature brain
      in regard to the glutamatergic and dopaminergic transmitter system are assessed.
      Thus, this mini-review highlights some progress but also an increased necessity
      for expanded pathogenetic research on a clinical scale in order to develop a
      solid foundation for adequate therapeutic strategies for the different life
      threatening consequences of TBI in infancy and childhood, which mainly have
      failed up to now.

PMID- 15581278
TI  - NMDA and age dependent cerebral hemodynamics after traumatic brain injury.
AB  - Activation of N-methyl-D-aspartate (NMDA) glutamatergic receptors elicits
      cerebrovascular dilation, may couple local cerebral metabolism to blood flow but
      contribute to excitotoxic neuronal cell death. While cerebral hemodynamics
      following traumatic brain injury may correlate with neurologic status, the role
      of NMDA vascular activity is uncertain in the sequelae of brain injury. NMDA
      dilation was impaired following fluid percussion brain injury (FPI) in an age
      dependent manner in the pig and the newly described opioid nociceptin/orphanin FQ
      (NOC/ oFQ) contributes to such impairment via the cyclooxygenase dependent
      generation of superoxide. Further, hypotensive pial artery dilation (PAD) was
      blunted after FPI but partially protected by pretreatment with the NMDA
      antagonist MK801. Cerebral blood flow (CBF) was reduced during normotension by
      FPI, further reduced by hypotension, but both were partially protected by MK801
      in the newborn. In contrast, blunted hypotensive PAD was protected significantly
      less by MK801 in the juvenile pig. Similarly, MK801 had less protective effect on
      normotensive and hypotensive CBF values post FPI in the juvenile. These data
      indicate that NMDA receptor activation contributes to impaired hypotensive
      cerebral hemodynamics following FPI in an age dependent manner. Further, these
      data suggest that NMDA receptor activation, NOC/oFQ, and prostaglandins
      dynamically interact to impair cerebral hemodynamics following FPI.

PMID- 15581279
TI  - Apoptotic neurodegeneration in the context of traumatic injury to the developing
      brain.
AB  - Head trauma is the leading cause of death and disability in the pediatric
      population. Some recent studies on neuropathological and biochemical features of
      traumatic injury to the developing brain revealed interesting aspects and
      potential targets for future research. Trauma triggers both excitotoxic and
      apoptotic neurodegeneration in the developing rat brain. Apoptotic
      neurodegeneration occurs in a delayed fashion over several days and contributes
      in an age-dependent fashion to neuropathologic outcome following head trauma,
      with the immature brain being exceedingly sensitive. Biochemical studies indicate
      that both the extrinsic and the intrinsic apoptotic pathways are involved in
      pathogenesis of apoptotic cell death following trauma in the developing brain and
      that caspase inhibition ameliorates apoptotic neurodegeneration in an infant head
      trauma model. Given the major contribution of apoptotic neurodegeneration to
      neuropathologic outcome following trauma to the developing brain, interference
      with apoptotic pathways may comprise a potential therapeutic target in pediatric
      traumatic brain injury.

PMID- 15581280
TI  - Traumatic injury in the developing brain--effects of hypothermia.
AB  - Little is known about the underlying mechanisms of head trauma in the developing
      brains, despite considerable social and economic impact following such injuries.
      Age has been shown to substantially influence morbidity and mortality. Children
      younger than 4 years of age had worse cognitive, motor, and brain atrophy
      outcomes than children 6 years of age and older. Younger children tend to more
      frequently suffer from diffuse cerebral swelling compared to adults. Typical
      autoptic findings also include axonal injury and ischemic neurodegeneration.
      These differences impact not only the primary response of the brain to injury but
      the secondary response as well. The complexity of damaging mechanisms in
      traumatic brain injury contributes to the problem of determining effective
      therapy. As an alternative/ adjunct to pharmacological approaches, hypothermia
      has been shown to be cerebroprotective in traumatized adult brains. Although a
      large number of animal studies have shown protective effects of hypothermia in a
      variety of damaging mechanisms after TBI, little data exist for young, developing
      brains. The injury mechanisms of TBI in the immature, effects of hypothermia
      following resuscitation on adult and immature traumatized brains, and some
      possible mechanisms of action of hypothermia in the immature traumatized brain
      are discussed in this review.

PMID- 15581281
TI  - Potential stem cell therapy and application in neurotrauma.
AB  - Traumatic brain injury results from a sudden and external physical insult to the
      head, which is often accompanied by motor and cognitive impairment. Neurotrauma
      is characterized not only by focal abnormalities, but rather by multifocal, or
      even global structural and functional disturbances of the brain network. The
      impact initially causes necrotic cell death in the underlying tissue, followed by
      apoptotic cell death in the surrounding tissue due to multiple subsequent events,
      such as ischemia, excitotoxicity and altered gene expression. These pathological
      conditions are associated with high morbidity and mortality. Despite the high
      medical and economical relevance of neurotrauma there are currently no sufficient
      treatments. Supplementary therapeutic strategies have to be established. Many
      types of stem cells have the ability to engraft diffusely and become integral
      members of structures throughout the host CNS. Intrinsic factors appear to derive
      spontaneously from stem cells and seem to be capable of neuroprotective and/or
      neuroregenerative functions. Furthermore stem cells can be readily engineered to
      express specific genes. Such observations suggest that stem cells might
      participate in reconstructing the molecular and cellular milieu of traumatized
      brains. In this paper, the state of stem cell research is reviewed and its
      possible application in neurotrauma will be discussed.

PMID- 15581282
TI  - Traumatic brain injury in children--clinical implications.
AB  - Traumatic brain injury (TBI) is the leading cause of death in childhood; however
      only very few studies focusing on the specific pathophysiology and treatment have
      been published to date. Head trauma is more likely in young children than in
      adults given the same deceleration of the body due to their large and heavy heads
      and weak cervical ligaments and muscles. Resulting brain injury is more severe
      due to their thin, pliable skulls and the yet unfused sutures. Accordingly,
      children below the age of 4 years have lower chances of a full recovery after
      severe TBI, although in general, neurologic recovery after severe brain injury in
      children is better than in adults. The time course of brain injury can be divided
      into two steps: primary and secondary injury. Primary brain injury exclusively
      results from the initial impact. In contrast, adverse physiologic conditions
      during recovery after head trauma may account for additional brain damage, which
      is then referred to as secondary brain injury. As primary brain injury can only
      be influenced by preventive measures, all therapeutic efforts during the post
      injury period focus on the reduction of secondary injury to the traumatized
      brain. Several mechanisms have been identified to be involved in the development
      of post-traumatic secondary brain injury, which render the rationale for the key
      treatment strategies. Three evidence based measures are of critical importance to
      prevent or minimize secondary brain injury: (1) avoid hypoxemia, (2) avoid post
      traumatic arterial hypotension, and (3) refer the traumatized child to an
      experienced trauma team at a center that provides the availability of special
      equipment, e.g. for surgical procedures and airway management, for this age
      group. For several other therapeutical means, e.g. hypothermia or specific
      surgical interventions, clinical evidence to date is insufficient to allow
      recommendation as rescue treatment for children at risk of severe neurological
      sequelae following TBI. This review discusses the clinical implication of
      pathophysiologic mechanisms of TBI in the developing brain according to the
      recent literature and current guidelines. It follows the clinical approach to a
      head injured child, that can be divided into three phases, i.e. initial
      assessment and stabilization, followed by first tier, and if necessary second
      tier therapeutic interventions to assure adequate oxygenation and perfusion of
      the brain.

PMID- 15581283
TI  - [Editorial].

PMID- 15581284
TI  - [Pharmacovigilance for veterinary drugs in Switzerland].
AB  - Pharmacovigilance is a system concerned with the acquisition, evaluation and
      classification of informations about suspected adverse drug reactions (SADR).
      Such a system was developed in Switzerland under the supervision of Swissmedic
      after the introduction of the federal law on therapeutic products on January 1st
      2002. By sending declarations about SADRs, veterinary practitioners play a
      central role in this scheme. The reports are processed according to international
      standards (ABON) and provide useful hints to enhance the safety of drug usage by
      both patients and owners. The system acquired 58 reports in its first complete
      year of operation (2003). Analysis of these reveals that trends observed in
      foreign countries are also applicable to Switzerland: most of the reports
      concerned the use of antiparasitic or antibiotic drugs in small animals. The
      first year also revealed a high percentage of declarations coming from the
      pharmaceutical companies and the authors would therefore like to encourage
      practitioners to take a more active part in this scheme.

PMID- 15581285
TI  - Evaluation of a standardised radiographic technique of the equine hoof.
AB  - Radiography of the equine hoof is often used to obtain a diagnosis. Quantitative
      interpretation, especially for research purposes requires high quality and
      accuracy of radiographs. The purpose of this study was to describe and evaluate a
      radiographic technique for the lateromedial (LM) and the dorsopalmar (DP) view of
      the equine hoof. Ten radiographs for each view from one cadaver limb and from
      both front feet in a standing horse were taken in order to assess repeatability
      of the radiographic technique. The method requires easy to use adjustable and
      portable equipment and strictly defined external radio opaque markers on the hoof
      capsule. The digitalised radiographs were processed and analysed with the
      software package Metron PX, measuring 13 parameters in the LM view and 10
      parameters in the DP view, respectively. Results show that with few exceptions
      measurements of these parameters revealed a coefficient of variation that was
      smaller than 0.05. It was concluded that this easy to use standardised
      radiographic technique ensures excellent accuracy and repeatability for both the
      LM and DP view. Hence, this method provides an adequate tool for quantitative
      assessment of the equine hoof, inter- and intraindividually.

PMID- 15581286
TI  - [Surgical and conservative methods for removing mummified fetuses in cattle].
AB  - The purpose of this study was to describe the findings and therapy in 4 cows and
      1 heifer with mummified fetus. All animals were admitted at the clinic after
      several unsuccessful therapies with prostaglandin F2alpha and local uterine
      infusions. All animals were in good condition. In case 1, diagnosis of mummified
      fetus could not be confirmed after manual rectal palpation and ultrasonography
      whereas cases 2, 4, 5 all had mummified fetus. In case 3, the fetus was in
      maceration. Initial therapy consisted of administration of prostaglandin F2alpha
      and prostaglandin E2 followed by repeated administration of prostaglandin E2.
      Mummies (length from apex to rump 13-32 cm) could be taken out within 3 to 6 days
      per vias naturales in cases 2, 4, 5 and in case 3, bones (maximal length 4 cm)
      could be unhinged. The structure in the uterus of case 1 could not be mobilised
      and was consequently removed under sight control using colpotomy followed by
      hysterotomy. Animals 2, 3, 4 and 5 were pregnant on the occasion of telephone
      inquiry. On the basis of our results, we recommend the conservative medical
      therapy with PGE2 for cases of mummified fetus. Colpotomy and hysterotomy are
      reserved as therapy feasible if the use of prostaglandin E2 is not successful.

PMID- 15581287
TI  - [Paraparesis in a dwarf goat: clarification by means of magnetic resonance
      imaging].
AB  - A 4-year old pygmy goat with chronic paraparesis of the hindlimbs was referred to
      the Ruminant Clinic of the University of Berne. The causative lesion was
      localized to the thoracolumbar spinal cord after a thorough clinical examination.
      Because a radiographic examination of the spine had not been diagnostic, magnetic
      resonance imaging (MRI) was performed. A mass compressing the spinal cord in the
      region of L2-L5 was detected. The goat was euthanized and autopsied, which
      allowed for the definitive diagnosis of lymphosarcoma. In addition to the changes
      in the lumbar area, further neoplastic masses were detected in the region of the
      thoracic vertebrae, near the thoracic aperture, on the lungs and on the
      pericardium. However, these processes had not yet caused clinical signs. MRI
      investigation allowed for the ante mortem diagnosis of an infiltrative mass in
      the spinal canal of this goat.

PMID- 15581290
TI  - [Sixth Congress of the European Wildlife Disease Association in Sweden].

PMID- 15581291
TI  - [Information about veterinary drug by-law].

PMID- 15581292
TI  - How many staff is enough?

PMID- 15581293
TI  - Misrepresents the results of research into walk-in centres.

PMID- 15581294
TI  - Board's eye view. Beyond the four-hour target.

PMID- 15581295
TI  - Care for the carers.

PMID- 15581296
TI  - Listening and learning from patients.

PMID- 15581297
TI  - Shared learning around the world.

PMID- 15581298
TI  - A walk on the wild side. Progress of walk-in centres.

PMID- 15581299
TI  - Alcohol screening in emergency departments.

PMID- 15581300
TI  - Managing whiplash injury.

PMID- 15581301
TI  - Early pressure ulcer development in spinal cord injured patients.

PMID- 15581303
TI  - [Years are spent in sleep!].

PMID- 15581304
TI  - [Better understanding of schizophrenia].

PMID- 15581305
TI  - [National survey of parents in the hospital].

PMID- 15581306
TI  - [Nutritional best practices in oncology: malnutrition and nutritional
      evaluation].

PMID- 15581307
TI  - [Sleep disorders (hypersomnia, somnolence].

PMID- 15581308
TI  - [Best use of the automatic blood pressure monitor].

PMID- 15581309
TI  - [Update on rabies].

PMID- 15581311
TI  - [Health personnel dossier. Art. L. 161-36-1 and s, Social Security Code, law n.
      2004-81 of August 13, 2004 concerning health insurance].

PMID- 15581312
TI  - [Enfuvirtide. Two injections per day for HIV].

PMID- 15581314
TI  - [Patient care team to prevent professional risks in handling patients].

PMID- 15581315
TI  - [Home care services: "4508 centers installed in June 2004"].

PMID- 15581316
TI  - [A way back, everyone wins].

PMID- 15581317
TI  - Diagnosis of dorsal displacement of the soft palate by sound spectrum analysis;
      the way ahead?

PMID- 15581318
TI  - Surgical repair of rib fractures in 14 neonatal foals: case selection, surgical
      technique and results.
AB  - REASONS FOR PERFORMING STUDY: Fractured ribs are encountered quite frequently in
      newborn Thoroughbred foals, often with fatal outcome. Surgical repair of
      fractures therefore requires consideration as a means of reducing mortality.
      OBJECTIVES: To evaluate the repair of rib fractures using internal fixation
      techniques in foals at 2 different equine hospitals following similar diagnostics
      and case selection. METHODS: The records of 14 foals that underwent internal
      fixation of fracture ribs were reviewed. Subject details, clinical presentation,
      diagnosis, surgical technique, post operative care and complications were
      recorded. Follow-up information was obtained in 7 foals. RESULTS: The fractured
      ribs were reduced and stabilised using reconstruction plate(s), self-tapping
      cortical screws and cerclage wire in 12 cases, Steinmann pins and cerclage wires
      in 1 case and both techniques in 1 case. Not every rib was reduced on each case.
      Surgical reduction was performed on an average of 2 ribs, range 1-3 ribs in each
      foal. At the time of writing, 4 foals had been sold, one age 2 years was in
      training and 2 others died from unrelated causes. CONCLUSIONS: Our data support
      the use of surgical stabilisation utilising reconstruction plates, self-tapping
      cortical screws and cerclage wire for selected cases of thoracic trauma in
      neonatal foals. The use of Steinmann pins may be suboptimal due to cyclic
      failure, implant migration and the potential for iatrogenic internal thoracic
      trauma. POTENTIAL RELEVANCE: Foals with existing extensive internal thoracic
      trauma resulting from rib fracture(s), or the potential for such trauma,
      previously considered to have a guarded to poor prognosis for survival, may be
      successfully managed with internal fixation of selected fracture sites.

PMID- 15581319
TI  - Longitudinal development of equine conformation from weanling to age 3 years in
      the Thoroughbred.
AB  - REASONS FOR PERFORMING STUDY: There is little information available to define
      conformational changes with age using an objective but practical method of
      recording specific body measurements. OBJECTIVE: To analyse conformation
      objectively in a population of racing Thoroughbreds and describe the changes from
      weanling to age 3 years. METHODS: Annual photographs were taken over 4 years and
      conformation measurements made from photographs using specific reference points
      marked on the horses. RESULTS: Correlation analysis revealed highly significant,
      moderate to strong relationships between long bone lengths and wither height for
      all ages. All long bone lengths showed moderate to strong relationships with each
      other for all ages. The front and rear pastern angles were significantly
      correlated with the angle of the dorsal surface of the front and rear hooves,
      respectively, for all. Wither height, croup height and length of neck topline,
      neck bottomline, scapula, humerus, radius and femur increased significantly from
      age 0-1 year and age 1-2 years. Hoof lengths (medial and lateral, right and left)
      grew significantly between the ages of 0 and 1 and 1 and 2 years, but decreased
      in length between age 2 and 3 years. Horses became more offset in the right limb
      between weanling and age 3 years, but the offset ratios did not change with age
      on the left limb. The angle of the scapula (I), shoulder and radiometacarpus
      significantly increased between all age groups (became more upright). The angle
      of the dorsal surface of the hooves (both front and hind) decreased significantly
      from ages 0 to 1 and 1 to 2 years, but showed no significant difference between
      ages 2 and 3 years. CONCLUSIONS: A strong relationship between long bone lengths
      and wither height for all ages supports the theory that horses are proportional.
      Longitudinal bone growth in the distal limb increased only 5-7% from weanling to
      age 3 years and is presumably completed prior to the yearling year. Several
      growth measures increased from ages 0 to 1 and 1 to 2 years, but did not increase
      from age 2-3 years; indicating that growth rate either slowed or reached a
      plateau at this time. POTENTIAL RELEVANCE: This study provides objective
      information regarding conformation and skeletal growth in the Thoroughbred which
      can be utilised for selection and recognition of significant conformational
      abnormalities.

PMID- 15581320
TI  - The role of conformation in musculoskeletal problems in the racing Thoroughbred.
AB  - REASONS FOR PERFORMING STUDY: The relationship of conformation to future
      potential injury is a standard approach in practise but, at present, is largely
      based on subjective observations. OBJECTIVE: To measure conformation in 3-year
      old Thoroughbreds and objectively test its relationship with the occurrence of
      musculoskeletal problems. METHODS: Conformation measurements were taken from
      photographs using specific reference points marked on the horses and processed on
      the computer. Clinical observations were recorded for each horse on a regular
      basis. Stepwise (forward) logistic regression analysis was performed to
      investigate the relationship between the binary response of the clinical outcomes
      probability and the conformation variables by the method of maximum likelihood.
      RESULTS: Clinical outcomes significantly (P<0.05) associated with conformational
      variables included effusion of the front fetlock, effusion of the right carpus,
      effusion of the carpus, effusion of the hind fetlock, fracture of the left or
      right carpus, right front fetlock problem and hind fetlock problem. CONCLUSIONS:
      Offset knees (offset ratio) contributed to fetlock problems. Long pasterns
      increased the odds of a fracture in the front limb. An increase in the carpal
      angle as viewed from the front (carpal valgus) may serve as a protective
      mechanism, as the odds for a carpal fracture and carpal effusion decreased with
      an increase in the carpal angle. POTENTIAL RELEVANCE: This study demonstrates
      relationships between conformation and musculoskeletal disease in the racehorse.
      The information may be useful in selection and management of the racing
      Thoroughbred.

PMID- 15581321
TI  - Endoscopic scoring of mucus quantity and quality: observer and horse variance and
      relationship to inflammation, mucus viscoelasticity and volume.
AB  - REASONS FOR PERFORMING STUDY: Endoscopic scoring of airway mucus quantity and
      quality has not been critically assessed. OBJECTIVES: To evaluate mucus scores
      for 1) observer- and horse-related variance and 2) association with inflammation,
      mucus viscoelasticity and measured volume. METHODS: Variance of scoring within
      and between observers and over time within horses were determined for airway
      mucus accumulation, apparent viscosity, localisation and colour, and correlations
      of mucus accumulation scores with neutrophil ratios in secretions. The
      relationship of accumulation score to measured volumes of 'artificial mucus' was
      investigated. Correlations of mucus accumulation, apparent viscosity and colour
      scores with measured viscoelasticity were tested. Viscoelasticity was compared
      between tracheal secretion samples collected ventrally and dorsally. RESULTS:
      Mucus accumulation scoring showed excellent interobserver agreement and moderate
      horse-related variance, was related to measured volumes of 'artificial mucus',
      and correlated well with neutrophilic airway inflammation. Scores of mucus
      viscosity, colour and localisation showed high observer-related variance. Mucus
      accumulation, apparent viscosity and colour scores did not correlate with
      measured tracheal mucus viscoelasticity, but dorsally-localised mucus showed 2
      fold higher measured viscoelasticity than ventrally-localised samples.
      CONCLUSIONS: Mucus accumulation scores are a reproducible measure of mucus
      volumes in the trachea. POTENTIAL RELEVANCE: Endoscopic scoring of mucus
      accumulation is a reliable clinical and research tool. In contrast, apparent
      viscosity, localisation and colour scores should be interpreted with caution.

PMID- 15581322
TI  - Immunological response to long-term transport stress in mature horses and effects
      of adaptogenic dietary supplementation as an immunomodulator.
AB  - REASONS FOR PERFORMING STUDY: Little information exists on the immunological
      effects of transport or the use of supplements to minimise transport stress.
      OBJECTIVES: To establish baseline ranges and evaluate immunophenotypic and
      functional changes associated with transport and a nutritional 'adaptogen'
      supplement. METHODS: Horses received either supplement (n = 10) or placebos (n =
      9) during the 30 day study. After 28 days in stalls, 12 horses (6 supplement; 6
      placebo) were transported for 24 h, then unloaded and recovered. Venous blood
      samples were collected on Days 1, 14 and 28 to establish baselines, and on Days
      28, 29 and 30 to examine changes during transport and recovery. RESULTS:
      Transport prompted elevations (P<0.05) in cortisol concentration, neutrophil
      count and white blood cell counts, while lymphocyte subpopulation counts (CD3+,
      CD4+, CD8+, CD21+) decreased (P<0.05). Normal phenotypic lymphocyte profiles
      returned within 24 h of recovery. Supplement effects on immunophenotype (CD21+
      and CD8+) were observed in stabled horses (P<0.05), but not in transported
      horses. CONCLUSIONS: These results provide insights into the immunological
      mechanisms associated with long-term transport. POTENTIAL RELEVANCE: The
      existence of a small window of immunological uncertainty follows long-term
      transportation, enhancing the potential risk of infectious disease in susceptible
      individuals.

PMID- 15581323
TI  - The displaced equine soft palate as a source of abnormal respiratory noise during
      expiration.
AB  - REASONS FOR PERFORMING STUDY: To develop the technique of respiratory sound
      analysis for the diagnosis of dorsal displacement of the equine soft palate.
      OBJECTIVES: To show that 1) the displaced soft palate can spontaneously vibrate
      in the presence of expiratory airflow; 2) the observed frequency of vibration can
      be detected in respiratory sound recordings; and 3) the frequency of vibrations
      measured in cadaveric specimens are similar to those obtained from audio spectra
      in exercising horses with DDSP. METHODS: Palatal movements and respiratory sounds
      were recorded from artificially ventilated cadaveric heads. The fundamental mode
      of palate vibrations calculated from high-speed videoendoscopic recordings was
      compared with frequencies detected in the audio spectra and with data collected
      from exercising horses with DDSP. RESULTS: Palate vibrations occurred when air
      was blown through the trachea. The fundamental mode of vibrations was present in
      the audio spectra and was not significantly different from those recorded in
      vivo. CONCLUSIONS: Vibrations of the soft palate are the probable source of
      expiratory sounds recorded in horses with DDSP. POTENTIAL RELEVANCE: This study
      strengthens the case for the application of respiratory sound analysis in the
      diagnosis of DDSP in exercising horses.

PMID- 15581324
TI  - A prospective cohort study to investigate risk factors for horse falls in UK
      hurdle and steeplechase racing.
AB  - REASONS FOR PERFORMING STUDY: Equine fatalities during racing continue to be a
      major welfare concern and falls at fences are responsible for a proportion of all
      equine fatalities recorded on racecourses. OBJECTIVES: To identify and quantify
      risk factors for horse falls in National Hunt (NH) racing and to report the
      frequency of falling and falling-associated fatalities. METHODS: A prospective
      cohort study was conducted on 2879 horse starts in hurdle and steeplechase races
      on 6 UK racecourses. Any horse that suffered a fall at a steeplechase or hurdle
      fence during the race was defined as a case. Data were obtained by interview and
      observations in the parade ring and from commercial databases. Multivariable
      logistic regression models, allowing for clustering at the level of the track,
      were used to identify the relationship between variables and the risk of falling.
      RESULTS: There were 124 falling cases (32 in hurdling and 92 in steeplechasing)
      identified. The injury risk of fallers was 8.9% and fatality risk 6.5%. Duration
      of journey to the racecourse, behaviour in the parade ring and weather at the
      time of the race were associated with falling in both hurdle and steeplechase
      racing. Age, amount of rainfall and going were also associated with falling in
      steeplechase racing. CONCLUSIONS: Falls at fences are significant contributors to
      equine fatalities during NH racing. Potentially modifiable risk factors
      identified were the condition of track surfaces and journey time to the
      racecourse. POTENTIAL RELEVANCE: It is hoped that information from this study may
      be used in future interventions to improve horse and jockey safety in racing. The
      study has also identified areas requiring further research, such as equine
      behaviour and its effect on racing performance, and the effect of light
      conditions on jumping ability.

PMID- 15581325
TI  - Ultrasonographic examination of the equine sacroiliac region.
AB  - REASONS FOR PERFORMING STUDY: Little information exists about the normal
      ultrasonographic appearance of the equine sacroiliac region, but knowledge of the
      ultrasonographic anatomy is necessary to understand the possible pathological
      changes in sacroiliac diseases. OBJECTIVES: The normal ultrasonographic
      appearance of soft tissues and bony structures of the sacroiliac region in horses
      was studied in order to establish clinically relevant reference parameters.
      METHODS: Thirteen cadaver specimens were examined using a transcutaneous approach
      above the tubera sacrale to image the dorsal sacroiliac ligament and the tendon
      of the longissimus dorsi muscle. A rectal approach was used to outline the
      sacroiliac joint and its adjacent structures. Thirteen sound horses with no
      history of back pain were examined following the same protocol as for the post
      mortem examinations. RESULTS: The tendon of the longissimus dorsi muscle can
      clearly be distinguished from the dorsal sacroiliac ligament, especially in
      longitudinal images. Transrectal examination of the sacroiliac joint consists of
      evaluation of the bony surfaces of the sacrum and ilium in comparison with the
      contralateral side. CONCLUSIONS: Ultrasonographic examination of the sacroiliac
      region provided clear images of the caudomedial border of the sacroiliac joint
      and its adjacent structures and is a useful aid in the diagnosis of sacroiliac
      joint diseases and adjacent lesions. The study has shown ultrasonography to be a
      useful method for examining and differentiating the longissimus dorsi muscle and
      the dorsal sacroiliac ligament at the level of the tubera sacrale. POTENTIAL
      RELEVANCE: Diagnostic ultrasound is available to most practitioners. These
      reference ultrasound parameters may help to improve the diagnosis of sacroiliac
      diseases.

PMID- 15581326
TI  - Use of intravenous flecainide in horses with naturally-occurring atrial
      fibrillation.
AB  - REASONS FOR PERFORMING STUDY: It has been reported that i.v. flecainide has a
      high efficacy for the treatment of experimentally-induced acute atrial
      fibrillation (AF) in horses and that its use is associated with minimal toxic
      side effects. OBJECTIVES: The objectives were to study the efficacy of i.v.
      flecainide as a treatment for atrial fibrillation in horses with naturally
      occurring AF. METHODS: Ten horses with naturally-occurring AF were treated with 2
      mg/kg bwt flecainide i.v. at a rate of 0.2 mg/kg bwt/min. In 3 horses, the
      infusion was continued at 0.05-0.10 mg/kg bwt/min until a total dose of 3.0 mg/kg
      bwt had been administered. Heart rate, QRS duration and average interval between
      fibrillation waves were measured before, during and following flecainide
      infusion. If conversion to normal sinus rhythm was not achieved, horses were
      treated with quinidine sulphate per os at a dose of 22 mg/kg bwt given every 2 h.
      RESULTS: None of the horses with chronic AF (n = 9) converted to sinus rhythm
      with flecainide i.v. The only horse treated successfully had acute AF of 12 days'
      duration. The QRS duration and fibrillation cycle length increased significantly
      (P = 0.006 and 0.002, respectively) during and following flecainide infusion.
      Heart rate did not increase significantly over time however, 3 horses developed
      heart rates in excess of 100 beats/min. Two horses developed a potentially
      dangerous ventricular dysrhythmia during the first 15 mins of treatment.
      Quinidine sulphate given per os restored sinus rhythm in 8 out of 9 horses, with
      minimal adverse effects. CONCLUSIONS: Although flecainide might be efficacious in
      cases of acute AF, it was not possible to restore sinus rhythm in horses with
      naturally-occurring chronic AF at the dosages used in this study. In 2 horses,
      2.0 mg/kg bwt flecainide was associated with potentially dangerous dysrhythmias.
      POTENTIAL CLINICAL RELEVANCE: Intravenous administration of 2 mg/kg bwt
      flecainide is unlikely to convert chronic AF in horses and could induce dangerous
      dysrhythmias.

PMID- 15581327
TI  - Effects of manipulating intrauterine growth on post natal adrenocortical
      development and other parameters of maturity in neonatal foals.
AB  - REASONS FOR PERFORMING STUDY: Intrauterine growth retardation (IUGR) impairs post
      natal adaptive responses and is associated with increased adrenocortical activity
      in many species. OBJECTIVES: To determine whether a restricted or enhanced
      intrauterine environment affects neonatal adaptation and adrenocortical function
      in horses. METHODS: Embryos from large (577 kg) Thoroughbred (TB) mares were
      transferred to smaller (343 kg) pony (P) mares and vice versa, to create a
      restricted (TB-in-P, n = 11) or enhanced (P-in-TB, n = 8) intrauterine
      environment. Control groups (TB-in-TB, n = 8; P-in-P, n = 7) were also included.
      RESULTS: Thirty foals were born live at full term (range 314-348 days) and 4 (3
      TB-in-P, 1 P-in-TB) were stillborn between 275 and 335 days. TB-in-P foals were
      significantly (P<0.05) lighter than TB-in-TB, but heavier than P-in-P foals. TB
      in-P foals took longer to first stand and suck and some had fetlock
      hyperextension and low (<4 g/l) plasma immunoglobulin G concentrations. Other
      foal groups showed normal behavioural responses. Haematological parameters were
      normal in all 4 groups of foals. Plasma ACTH levels were high at birth and plasma
      cortisol concentrations increased after delivery and returned to baseline within
      6 h post partum in all but the TB-in-P foals, which had elevated levels until 48
      h post partum. Plasma cortisol concentrations increased in all groups following
      exogenous ACTH administered on Days 1 and 5 postpartum. CONCLUSIONS: The TB-in-P
      foals showed IUGR and impaired post natal adaptive responses with basal
      hypercortisolaemia. POTENTIAL RELEVANCE: Foals born following IUGR may require
      clinical assistance in the early post natal period, but appear mature with
      respect to adrenocortical function.

PMID- 15581328
TI  - Tegaserod (HTF 919) stimulates gut motility in normal horses.
AB  - REASONS FOR PERFORMING STUDY: It has been shown that the selective 5-HT4 receptor
      agonist tegaserod induces an increase in frequency and amplitude of contractions
      in isolated muscle preparations of equine ileum and pelvic flexure. OBJECTIVES:
      To investigate the effects of tegaserod on gut motility and transit of spheres in
      normal horses. METHODS: Six mature Freiberger horses were kept under standardised
      conditions. Effects of tegaserod (0.02 mg/kg bwt i.v. b.i.d. for 2 days) or
      vehicle on intestinal transit of barium-filled spheres, defaecation and gut
      sounds were studied in a cross-over design. Spheres were given via stomach tube
      prior to the first dosing of tegaserod or vehicle. Faeces were collected every 3
      h and spheres eliminated were identified radiologically in the faeces. RESULTS:
      Tegaserod significantly accelerated the gastrointestinal (GI) transit time of
      spheres and increased the frequency of defaecation and scores of gut sounds
      compared to vehicle. The compound was well tolerated; no effects on behaviour,
      body temperature, heart rate, respiratory rate and clinical laboratory data were
      observed. CONCLUSIONS: Tegaserod efficaciously stimulated motility and accelerate
      GI transit in healthy horses. POTENTIAL RELEVANCE: Tegaserod may offer
      therapeutic potential in horses suffering from impaction or paralytic ileus.

PMID- 15581329
TI  - Respiratory and metabolic effects of massive administration of isotonic saline
      solution in heaves-affected and control horses.
AB  - REASONS FOR PERFORMING STUDY: It has been suggested that rapid administration of
      isotonic saline solution relieves airway obstruction in heaves-affected horses,
      but the efficacy and tolerability of this treatment is poorly documented.
      OBJECTIVES: To determine the respiratory and metabolic effects of a rapid
      administration of isotonic saline solution in control horses and those with
      heaves. METHODS: Thirty litres isotonic saline solution were administered i.v. to
      5 control (Group C) and 9 heaves-affected horses (Group H). Pulmonary function
      testing and arterial blood gas analysis were performed prior to saline infusion,
      at 90 and 180 mins after starting the infusion, and 1, 3, 6 and 10 days later.
      PCV, plasma total solids, plasma electrolytes (Na+, Cl- and K+) and venous blood
      gas analysis were performed prior, during and after saline infusion. RESULTS:
      Rapid saline administration was shown to have no beneficial effects on lung
      function during infusion in Group H. On the contrary, they had significantly
      increased pulmonary resistance (RL) at 180 mins following the initiation of
      saline administration compared to baseline. In Group C, saline administration
      resulted in a significant increase in RL at 180 mins and a significant decrease
      in PaO2 at 90 mins. These results suggest a transient decrement in lung function
      caused by rapid saline administration. Group H had a metabolic alkalosis with
      hypochloraemia at baseline compared to control horses. This resolved following
      i.v. saline administration and returned to baseline within 6 h after treatment
      had been discontinued. CONCLUSION: The administration of saline to Group H did
      not improve airway function significantly, but resulted in mild and transient
      side effects. POTENTIAL RELEVANCE: Rapid administration of isotonic saline alone
      is not an effective therapy for heaves in horses.

PMID- 15581330
TI  - Further studies on the ability of glucosamine and chondroitin sulphate to
      regulate catabolic mediators in vitro.

PMID- 15581331
TI  - Ultrasonographic control of navicular bursa injection.

PMID- 15581332
TI  - Valuable lessons from VALUE.

PMID- 15581333
TI  - Hypertension and microalbuminuria: the new detrimental duo.
AB  - Excretion of albumin with urine (UAE) in small amounts, i.e. microalbuminuria
      (MAU), also referred to as "incipient nephropathy", has long been considered a
      marker of early nephropathy and increased cardiovascular risk in the specific
      setting of diabetes mellitus. However, numerous clinical studies found an
      association between MAU and other cardiovascular risk factors, target organ
      damage and risk of cardiovascular disease in clinical contexts different from
      diabetes and including arterial hypertension. The present article reviews the
      available evidence on the clinical value of MAU in subjects with primary
      hypertension. In these subjects, prevalence of MAU varied from about 4% to 46%
      across different studies and these differences may be explained by the huge intra
      individual variability in UAE, discrepancies in the technique of measurement and
      different definitions of MAU. A direct and continuous association between UAE and
      blood pressure (BP) has been found in many studies. A continuous association
      between UAE and left ventricular mass has also been found in most studies. In
      contrast, it is not yet clear whether the association between UAE and other
      factors including age, gender, smoking, ethnicity, insulin resistance, lipids and
      obesity is independent or mediated by confounders, particularly BP. From a
      prognostic standpoint, several longitudinal studies showed an association between
      MAU and the risk of future cardiovascular disease. Of particular note, in some of
      these studies the incidence of major cardiovascular events progressively
      increased with UAE starting below the conventional MAU thresholds. Thus, besides
      being a direct risk factor for progressive renal damage, MAU can be considered a
      marker, which integrates and reflects the long-term level of activity of several
      other detrimental factors on cardiovascular system. Antihypertensive treatment
      reduces UAE and such effect may be detected after just a few days of treatment.
      Among available antihypertensive drugs, angiotensin-converting enzyme (ACE)
      inhibitors and the angiotensin II receptor antagonists seem to be superior to
      other antihypertensive drugs in reducing UAE. The dual blockade of the renin
      angiotensin system with an ACE inhibitor and an angiotensin II receptor
      antagonist is a new and promising approach to control UAE in hypertensive
      patients. Determination of MAU is recommended in the initial work-up of subjects
      with primary hypertension.

PMID- 15581334
TI  - The two-edged sword: controlling hypertension without destroying the patient.

PMID- 15581335
TI  - Reproducibility of blood pressure variability, white-coat effect and dipping
      pattern in untreated, uncomplicated and newly diagnosed essential hypertension.
AB  - OBJECTIVE: To investigate the reproducibility of blood pressure (BP) variability,
      white-coat effect (WCE) and nocturnal dipping pattern in untreated patients with
      uncomplicated essential hypertension using 24-hour ambulatory BP monitoring
      (ABPM). METHODS: Seventy-five newly diagnosed, untreated essential hypertensive
      subjects (54 men, 21 women 47.6 +/- 9.3 years) were recruited for the study based
      on conventional measured BP from a total of 180 patients referred for ABPM. Of
      these, 65 patients underwent repeated ABPM after 4 weeks observation without
      treatment. Reproducibility of BP, nocturnal dipping pattern, WCE and BP
      variability were assessed using different methods. RESULTS: The average 24-hour
      BP (140.8 +/- 11.9/91.8 +/- 6.4 vs. 140.5 +/- 14.5/90.7 +/- 7.6 mmHg, ns) or PP
      (49.6 +/- 10.8 vs. 49.8 +/- 9.8 mmHg, ns) did not change, nor did daytime BP or
      PP. The WCE diminished significantly during the observation period (reduction in
      SBP WCE delta8.2 +/- 12.5 mmHg, p < 0.0001, in DBP WCE, delta3.3 +/- 9.2 mmHg, p
      = 0.008 and in PP WCE delta4.8 +/- 11.2 mmHg, p = 0.002). Variability in SBP, DBP
      and PP decreased consistently and significantly during the observation period.
      The nocturnal dipping pattern was unchanged in 82% of the patients. In 12% non
      dipping pattern was converted to dipping pattern after repeated measurement.
      CONCLUSION: Average ABPs are highly reproducible in patients with uncomplicated
      essential hypertension of limited duration. Similarly, nocturnal dipping pattern
      reproduced satisfactorily. These measures have important clinical applicability.
      The white-coat effect as well as variability are greatly attenuated during
      repeated measurements, and these measures may thus be of less utility in clinical
      practice.

PMID- 15581336
TI  - Is hypertensive response in treadmill testing better identified with correction
      for working capacity? A study with clinical, echocardiographic and ambulatory
      blood pressure correlates.
AB  - Hypertensive response in treadmill testing is associated with the development of
      hypertension, but it is still unclear if it is better identified by systolic or
      diastolic response, and measured directly or corrected by working capacity. We
      investigated 75 patients with normal office blood pressure through a treadmill
      testing, ambulatory blood pressure (ABP) monitoring, and two-dimensional Doppler
      echocardiogram. Characteristics associated with systolic blood pressure (SBP)
      response corrected by the estimated metabolic equivalent (MET) were identified in
      multiple linear regression models. SBP response was associated more consistently
      with age, body mass index (BMI), systolic ABP and left ventricular posterior wall
      thickness (p < 0.001) than diastolic response in the bivariate analysis,
      especially when corrected by MET. Age, BMI and nightly SBP were independently
      associated with SBP response corrected by MET in the multivariate analysis.
      Individuals from the top tertile of SBP response corrected by MET (> or =11.3
      mmHg/MET) were older and had higher BMI, ABP and left ventricular septal and
      posterior wall thickness than individuals classified in the lower tertiles. These
      differences were more pronounced than the differences observed between
      individuals with and without a peak exercise blood pressure higher than 210 mmHg.
      We concluded that individuals with a high blood pressure response in treadmill
      testing have higher BMI, left ventricular posterior wall thickness and SBP
      measured by ABP monitoring than individuals without such a response. These
      differences were stronger when the variation of blood pressure during exercise
      was corrected by the amount of work performed.

PMID- 15581337
TI  - Is the nocturnal fall in blood pressure reduced in essential hypertensive
      patients with metabolic syndrome?
AB  - OBJECTIVE: The aim of this study was to examine whether an impaired reduction in
      nocturnal blood pressure (BP), defined on the basis of two periods of ambulatory
      BP monitoring (ABPM), is present in hypertensive patients with metabolic
      syndrome, as defined by the NCEP criteria. METHODS: 460 grade 1 and 2 untreated
      essential hypertensives (mean age 45.9 +/- 11.9 years) referred for the first
      time to our outpatient hospital clinic underwent the following procedures: 1)
      medical history and physical examination; 2) repeated clinic BP measurements; 3)
      routine examinations; 4) ABPM over two 24-hour periods within 4 weeks. Metabolic
      syndrome was defined as at least three of the following alterations: increased
      waist circumference, increased triglycerides, decreased HDL-cholesterol,
      increased BP, or high fasting glucose. Nocturnal dipping was defined as a night
      time reduction in average SBP and DBP >10% compared to average daytime values.
      RESULTS: The 135 patients with metabolic syndrome (group I) were similar for age,
      gender and known duration of hypertension to the 325 patients without it (group
      II). There were no significant differences between the two groups in average 48
      hour, daytime, night-time SBP/DBP values and the percentage nocturnal SBP and DBP
      decrease (-17.7 / -15.7 vs. -18.4 / -16.2, p = ns). A reproducible nocturnal
      dipping (decrease in BP >10% from mean daytime in both ABPM periods) and non
      dipping profile (decrease in BP < or =10% in both ABPM periods) was found in 74
      (54.8%) and 29 (21.4%) in group I and in 169 (52.1%) and 73 (22.4%) in group II,
      respectively (p = ns); 32 patients (23.7%) in group I and 83 patients (25.5%) in
      group II had a variable dipping profile (p = ns). CONCLUSIONS: This study shows
      that no significant difference exists in nocturnal BP patterns, assessed by two
      ABPMs, in untreated essential hypertensive patients with metabolic syndrome
      compared to those without it.

PMID- 15581338
TI  - Associations among plasma adiponectin, hypertension, left ventricular diastolic
      function and left ventricular mass index.
AB  - OBJECTIVE: The purpose of this study was to characterize the relationships among
      plasma adiponectin, essential hypertension, left ventricular diastolic function
      and left ventricular hypertrophy. METHODS AND RESULTS: Plasma adiponectin
      concentration was assessed by radioimmunoassay, and body mass index (BMI) was
      measured in 275 patients (138 women and 137 men). Various echocardiographic
      parameters such as deceleration time (DT) and isovolumetric relaxation time
      (IVRT) were measured by using echocardiograms. The authors calculated left
      ventricular mass index (LVMI) and E/A ratio. Pulse wave velocity (PWV) was
      calculated by dividing the distance between the left subclavian artery ostium and
      the tip of the femoral sheath with the time interval between two pulse waves. The
      plasma adiponectin concentration of the hypertensive group was significantly
      lower than that of the non-hypertensive group (9.9 +/- 9.8 microg/ml vs. 12.9 +/-
      9.5 microg/ml, p = 0.019). PWV in the hypertensive group was 12.0 +/- 3.9 m/s
      compared with 9.3 +/- 2.8 m/s in the normotensive group (p < 0.001). LVMI in the
      hypertensive group was 135.1 +/- 35.4 g/m2 compared with 100.5 +/- 18.7 g/m2 in
      the normotensive group (p < 0.001). E/A ratio (0.8 +/- 0.3 vs. 1.1 +/- 0.4, p =
      0.041) was lower in the hypertensive group. DT (200.0 +/- 61.2 ms vs. 177.3 +/-
      40.8 ms, p = 0.048) and IVRT (106.9 +/- 25.4 vs. 91.3 +/- 27.6 ms, p = 0.243)
      were higher in the hypertensive group. Plasma adiponectin showed an inverse
      correlation with LVMI (r = -0.525; p < 0.001) and PWV (r = -0.557; p < 0.001),
      IVRT (r = -0.485; p = 0.008), and showed a positive correlation with E/A ratio (r
      = 0.359; p < 0.001). Multiple regression analyses showed that PWV and plasma
      adiponectin were able to explain the 73.3% of LVMI variability (r = 0.856; p <
      0.001). CONCLUSION: The results suggest that a decrease in plasma adiponectin
      concentration is associated with the progression of left ventricular hypertrophy
      with diastolic dysfunction.

PMID- 15581339
TI  - Serum leptin and myocardial infarction in hypertension.
AB  - The adipose tissue-derived hormone leptin is among the physiologic processes
      involved in cardiovascular regulation. The aim of the present study was to
      elucidate if serum leptin may predict cardiovascular risk, particularly
      myocardial infarction (MI), in hypertensive men and women. In a prospective study
      cohort of hypertensive men and women, serum leptin was compared in 171 patients
      with MI and in 342 matched controls. The mean serum concentration of leptin was
      25.1 +/- 20.0 ng/ml in the MI patients and 20.0 +/- 16.6 ng/ml in the controls (p
      = 0.007). The association between serum leptin and MI was independent of
      traditional risk factors. Leptin concentrations were higher in women than in men.
      In women, serum leptin was the most important predictor of MI. The present study
      indicates that serum leptin is associated with MI in a hypertensive population.
      Leptin concentrations may be of practical importance when estimating the risk of
      MI, especially in women, where leptin was found to be the most important
      predictor for MI.

PMID- 15581340
TI  - Ambulatory monitoring predicts development of drug-treated hypertension in
      subjects with high normal blood pressure.
AB  - BACKGROUND: High normal blood pressure (HNBP), i.e. blood pressure (BP) > or =
      130/85 mmHg and <140/90 mmHg, is an important predictor of progression to
      established hypertension. DESIGN: The purpose of this retrospective study was the
      evaluation of the predictive value of ambulatory blood pressure monitoring (ABPM)
      for the development of drug-treated hypertension in subjects with HNBP and other
      risk factors. METHODS: We studied 127 subjects (69 M, 58 F, age 50 +/- 14 years):
      59 subjects had normal BP (NBP: < 130/85 mmHg), 68 subjects had systolic and/or
      diastolic HNBP. All the subjects underwent ABPM. There were 21/68 (30.9%)
      subjects in the HNBP group vs. 1/59 (1.7%) in the NBP group with an elevated
      (>135/85 mmHg) daytime ambulatory blood pressure (ABP) (p < 0.01). RESULTS: After
      an average follow-up of 103 +/- 28 months, 27 subjects (39.7%) in the HNBP group
      and 4 subjects (6.8%) in the NBP group developed drug-treated hypertension (p <
      0.01). An elevated daytime ABP correctly predicted development of drug-treated
      hypertension in 17/21 subjects (81%) of the HNBP group and in the only subject of
      the NBP group. Development of drug-treated hypertension was associated with
      higher office and ambulatory BP (p < 0.01) and pulse pressures (p < 0.05), longer
      follow-up (p < 0.05) and higher prevalence of hypercholesterolaemia and smoking
      (p < 0.01). CONCLUSIONS: We conclude that ABPM correctly predicts development of
      drug-treated hypertension in most subjects who were identified early as having a
      daytime mean ABP >135/85 mmHg. ABPM appears to be a useful clinical tool in the
      early diagnosis of hypertension in subjects with metabolic risk factors and
      smoking.

PMID- 15581341
TI  - Effects of crossed leg on blood pressure.
AB  - It is known that many factors influence an individual's blood pressure
      measurement. However, guidelines for accurately measuring blood pressure
      inconsistently specify that the patient should keep feet flat on the floor. The
      purpose of this study was to examine the effects of a crossed leg position on
      blood pressure in a Turkish sample. A prospective study of 238 subjects with an
      unmedicated high-normal blood pressure, stage 1 or stage 2 hypertension was
      conducted. After obtaining informed consent, subjects positioned their feet flat
      on the floor while their blood pressure was being measured. After 3 min, the
      blood pressure was measured again with the subject's leg crossed at the knee.
      Mean values of blood pressure were compared by t-test between two measurements.
      Statistical significance for all analysis was taken at the 5% level. The results
      indicated that both systolic and diastolic blood pressure increased significantly
      with the crossed leg position. Crossing the leg at the knee results in a
      significant increase in blood pressure. When blood pressure is measured, subjects
      should be instructed to have feet flat on the floor to eliminate a potential
      source of error.

PMID- 15581342
TI  - Resolving the excited state equilibrium of peridinin in solution.
AB  - The carotenoid peridinin is abundant in the biosphere, as it is the main pigment
      bound by the light-harvesting complexes of dinoflagellates, where it collects
      blue and green sunlight and transfers energy to chlorophyll a with high
      efficiency. Its molecular structure is particularly complex, giving rise to an
      intricate excited state manifold, which includes a state with charge-transfer
      character. To disentangle the excited states of peridinin and understand their
      function in vivo, we applied dispersed pump-probe and pump-dump-probe
      spectroscopy. The preferential depletion of population from the intramolecular
      charge transfer state by the dump pulse demonstrates that the S(1) and this
      charge transfer state are distinct entities. The ensuing dump-induced dynamics
      illustrates the equilibration of the two states which occurs on the time scale of
      a few picoseconds. Additionally, the dump pulse populates a short-lived ground
      state intermediate, which is suggestive of a complex relaxation pathway, probably
      including structural reorientation or solvation of the ground state. These
      findings indicate that the unique intramolecular charge transfer state of
      peridinin is an efficient energy donor to chlorophyll a in the peridinin
      chlorophyll-protein complex and thus plays a significant role in global light
      harvesting.

PMID- 15581343
TI  - An intersheet packing interaction in A beta fibrils mapped by disulfide cross
      linking.
AB  - Most models for the central cross-beta folding unit in amyloid fibrils of the
      Alzheimer's plaque protein Abeta align the peptides in register in H-bonded,
      parallel beta-sheet structure. Some models require the Abeta peptide to undergo a
      chain reversal when folding into the amyloid core, while other models feature
      very long extended chains, or zigzag chains, traversing the protofilament. In
      this paper we introduce the use of disulfide bond cross-linking to probe the fold
      within the core and the packing interactions between beta-sheets. In one
      approach, amyloid fibrils grown under reducing conditions from each of three
      double cysteine mutants (17/34, 17/35, and 17/36) of the Abeta(1-40) sequence
      were subjected to oxidizing conditions. Of these three mutants, only the
      Leu17Cys/Leu34Cys peptide could be cross-linked efficiently while resident in
      fibrils. In another approach, double Cys mutants were cross-linked as monomers
      before aggregation, and the resulting fibrils were assessed for stability,
      antibody binding, dye binding, and cross-seeding efficiency. Here too, fibrils
      from the 17/34 double Cys mutant most closely resemble wild-type Abeta(1-40)
      fibrils. These data support models of the Abeta fibril in which the Leu17 and
      Leu34 side chains of the same peptide pack against each other at the beta-sheet
      interface within the amyloid core. Related cross-linking strategies may reveal
      longer range spatial relationships. The ability of the cross-linked 17/35 double
      Cys mutant Abeta to also make amyloid fibrils illustrates a remarkable plasticity
      of the amyloid structure and suggests a structural mechanism for the generation
      of conformational variants of amyloid.

PMID- 15581344
TI  - Molecular-level organization of saturated and polyunsaturated fatty acids in a
      phosphatidylcholine bilayer containing cholesterol.
AB  - Cholesterol's preference for specific fatty acid chains is investigated at the
      atomic level in a 20 ns molecular dynamics computer simulation of a lipid bilayer
      membrane consisting of cholesterol and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3
      phosphocholine (SDPC) in a 1:3 ratio. These simulations reproduce experimental
      measurements suggesting that cholesterol prefers to be solvated by saturated acyl
      chains and has a low affinity for polyunsaturated fatty acids. Analyses of the
      simulation trajectory provide a detailed picture of both the transverse and
      lateral structures of the lipid bilayer membrane, along with a description of
      lipid and cholesterol dynamics at high temporal resolution. Comparison with a
      previous simulation of a pure phospholipid bilayer allows an atomic-level
      description of the changes in membrane structure and dynamics resulting from
      incorporation of cholesterol. The observed differential cholesterol interactions
      with saturated and polyunsaturated lipids provide a mechanism for the formation
      of laterally inhomogeneous membranes; thus, the simulation provides molecular
      level insight into the formation of lipid rafts.

PMID- 15581345
TI  - Origins of helix-coil switching in a light-sensitive peptide.
AB  - Intramolecular cross-linking of peptides by the light-sensitive compound
      diiodoacetamideazobenzene has been shown to permit reversible photocontrol of the
      helix-coil transition. Cross-linking between Cys residues spaced at i and i + 7
      positions with the trans form of the linker was found to produce a decreased
      helix content compared to that of the non-cross-linked peptide.
      Photoisomerization to the cis form of the linker led to substantially higher
      helix content than in the non-cross-linked peptide. Detailed conformational
      analysis of the system leads to the conclusion that photocontrol of helix content
      does not involve specific interactions between the linker and the peptide.
      Instead, the change in peptide helix content caused by photoisomerization can be
      predicted by comparing the length ranges of the cis and trans forms of the linker
      with the expected distance distribution of the Cys attachment points in the
      intrinsic conformational ensemble of the peptide. The analysis presented here
      should help to guide the use of these and related linkers for the conformational
      control of a variety of peptide and protein systems.

PMID- 15581346
TI  - Peroxyl radical mediated oxidative DNA base damage: implications for lipid
      peroxidation induced mutagenesis.
AB  - Endogenous DNA damage induced by lipid peroxidation is believed to play a
      critical role in carcinogenesis. Lipid peroxidation generates free radical
      intermediates (primarily peroxyl radicals, ROO(*)) and electrophilic aldehydes as
      the principal genotoxicants. Although detailed information is available on the
      role of aldehyde base adducts in mutagenesis and carcinogenesis, the contribution
      of peroxyl radical mediated DNA base damage is less well understood. In the
      present study we have mapped oxidative base damage induced by peroxyl radicals in
      the supF tRNA gene and correlated this information with peroxidation-induced
      mutations in several human fibroblast cell lines. Nearly identical patterns of
      oxidative base damage were obtained from reaction of DNA with either peroxidizing
      arachidonic acid (20:4omega6) or peroxyl radicals generated by thermolysis of
      ABIP in the presence of oxygen. Oxidative base damage primarily occurred at G and
      C. Transversions at GC base pairs in the supF gene were the major base
      substitution detected in all cell lines. Peroxyl radical induced tandem mutations
      were also observed. Many mutation hot spots coincided with sites of mapped
      oxidative lesions, although in some cases hot spots occurred adjacent to the
      damaged base. Evidence is presented for the involvement of 8-oxodG in the
      oxidation of DNA by ROO(*). These results are used to interpret some key features
      of previously published mutation spectra induced by lipid peroxidation in human
      cells.

PMID- 15581347
TI  - Impact of the C1' configuration of abasic sites on DNA duplex structure.
AB  - Naturally occurring abasic sites in DNA exist as an equilibrium mixture of the
      aldehyde, the hydrated aldehyde, and the hemiacetal forms (dominant). The
      influence of the configuration of the C1' hydroxyl group of the hemiacetal form
      on duplex structure and abasic site repair has been examined using novel
      carbocyclic analogues. Both the alpha- and beta-forms of this novel abasic site
      were introduced into oligomeric DNA using the standard DMT-phosphoramidite
      approach in an automated solid-phase synthesizer. Solution structures of the
      d(CGTACXCATGC).d(GCATGAGTACG) duplex (where X is the alpha- or beta-anomer of the
      carbocyclic abasic site analogue) were determined by NMR spectroscopy and
      restrained molecular dynamics simulations. The structures were only minimally
      perturbed by the presence of either anomer of the abasic site. All residues
      adopted an anti conformation, and Watson-Crick alignments were observed on all
      base pairs of the duplexes. At the lesion site, the abasic residues and their
      partner adenines showed increased dynamic behavior but adopted intrahelical
      positions in the final refined structures. Incision of duplexes having the alpha-
      or beta-anomer of the carbocyclic abasic site by human AP endonuclease showed
      that the enzyme recognizes both configurations of the lesion and nicks the DNA
      backbone with similar efficiency. Our results challenge the suggestion that Ape1
      is stereoselective and imply a plasticity at the active site of the enzyme for
      accommodating either anomer of the lesion.

PMID- 15581348
TI  - Heterotrimeric type I collagen C-telopeptide conformation as docked to its helix
      receptor.
AB  - The amino (N-telo) and carboxyl (C-telo) telopeptides of type I collagen play
      crucial roles, in vivo and in vitro, in the assembly of collagen fibrils,
      regulating the axial alignment of the molecules within a fibril, azimuthal
      orientations of neighboring molecules, and cross-link formation. High-resolution
      structures of the telopeptides are not available from X-ray diffraction studies,
      but computational methods permitted prediction of the N-telo structure within a
      fibril. Here, using a suite of molecular modeling software, the more complex
      heterotrimeric C-telo of human type I collagen has been built from the correct
      sequences and energy minimized and the energy minimum confirmed by molecular
      dynamics. The receptor triple helix was modeled on the basis of the Protein Data
      Bank coordinates of a collagen-like sequence. Docking of the heterotrimeric C
      telopeptide to its receptor showed that hydrophobic interactions involving the
      short alpha2 C-telopeptide are crucial determinants of its azimuthal orientation
      within the docked structure. A docked C-telo can interact with only one
      neighboring helix. The two alpha1(I) C-telo chains in the alpha1(Alpha)-alpha2
      alpha1(B) chain stagger do not have identical docked conformations, and one of
      the alpha1(I) C-telo chains appears to be favored for formation of a cross-link
      between its K(16C) and a helix K87. Prior studies showed that a docked N
      telopeptide can interact with two adjacent collagen monomers, forming a tightly
      packed region. A recent X-ray analysis showed the N- and C-telo regions pack
      differently, with the C-telo region being less densely packed than N-telo
      regions. This difference between N- and C-telopeptide docked structures
      demonstrates how unique and specific packing can occur in the fibril at each
      boundary of the type I collagen gap region.

PMID- 15581349
TI  - Lysine 5 and phenylalanine 9 of the factor IX omega-loop interact with
      phosphatidylserine in a membrane-mimetic environment.
AB  - The binding of factor IX to cell membranes requires a structured N-terminal omega
      loop conformation that exposes hydrophobic residues for a highly regulated
      interaction with a phospholipid. We hypothesized that a peptide comprised of
      amino acids Gly4-Gln11 of factor IX (fIX(G4)(-)(Q11)) and constrained by an
      engineered disulfide bond would assume the native factor IX omega-loop
      conformation in the absence of Ca(2+). The small size and freedom from
      aggregation-inducing calcium interactions would make fIX(G4)(-)(Q11) suitable for
      structural studies for eliciting details about phospholipid interactions.
      fIX(G4)(-)(Q11) competes with factor IXa for binding sites on phosphatidylserine
      containing membranes with a K(i) of 11 microM and inhibits the activation of
      factor X by the factor VIIIa-IXa complex with a K(i) of 285 microM. The NMR
      structure of fIX(G4)(-)(Q11) reveals an omega-loop backbone fold and side chain
      orientation similar to those found in the calcium-bound factor IX Gla domain,
      FIX(1-47)-Ca(2+). Dicaproylphosphatidylserine (C(6)PS) induces HN, Halpha
      backbone, and Hbeta chemical shift perturbations at residues Lys5, Leu6, Phe9,
      and Val10 of fIX(G4)(-)(Q11), while selectively protecting the NHzeta side chain
      resonance of Lys5 from solvent exchange. NOEs between the aromatic ring protons
      of Phe9 and specific acyl chain protons of C(6)PS indicate that these
      phosphatidylserine protons reside 3-6 A from Phe9. Stabilization of the
      phosphoserine headgroup and glycerol backbone of C(6)PS identifies that
      phosphatidylserine is in a protected environment that is spatially juxtaposed
      with fIX(G4)(-)(Q11). Together, these data demonstrate that Lys5, Leu6, Phe9, and
      Val10 preferentially interact with C(6)PS and allow us to correlate known
      hemophilia B mutations of factor IX at Lys5 or Phe9 with impaired
      phosphatidylserine interaction.

PMID- 15581350
TI  - Analysis of human cytochrome P450 2C8 substrate specificity using a substrate
      pharmacophore and site-directed mutants.
AB  - The structural determinants of substrate specificity of human liver cytochrome
      P450 2C8 (CYP2C8) were investigated using site-directed mutants chosen on the
      basis of a preliminary substrate pharmacophore and a three-dimensional (3D)
      model. Analysis of the structural features common to CYP2C8 substrates exhibiting
      a micromolar K(m) led to a substrate pharmacophore in which the site of oxidation
      by CYP2C8 is 12.9, 8.6, 4.4, and 3.9 A from features that could establish ionic
      or hydrogen bonds, and hydrophobic interactions with protein amino acid residues.
      Comparison of this pharmacophore with a 3D model of CYP2C8 constructed using the
      X-ray structure of CYP2C5 suggested potential CYP2C8 amino acid residues that
      could be involved in substrate recognition. Twenty CYP2C8 site-directed mutants
      were constructed and expressed in yeast to compare their catalytic activities
      using five CYP2C8 substrates that exhibit different structures and sizes
      [paclitaxel, fluvastatin, retinoic acid, a sulfaphenazole derivative (DMZ), and
      diclofenac]. Mutation of arginine 241 had marked effects on the hydroxylation of
      anionic substrates of CYP2C8 such as retinoic acid and fluvastatin. Serine 100
      appears to be involved in hydrogen bonding interactions with a polar site of the
      CYP2C8 substrate pharmacophore, as shown by the 3-4-fold increase in the K(m) of
      paclitaxel and DMZ hydroxylation after the S100A mutation. Residues 114, 201, and
      205 are predicted to be in close contact with substrates, and their mutations
      lead either to favorable hydrophobic interactions or to steric clashes with
      substrates. For instance, the S114F mutant was unable to catalyze the 6alpha
      hydroxylation of paclitaxel. The S114F and F205A mutants were the best catalysts
      for retinoic acid and paclitaxel (or fluvastatin) hydroxylation, respectively,
      with k(cat)/K(m) values 5 and 2.1 (or 2.4) times higher, respectively, than those
      found for CYP2C8. Preliminary experiments of docking of the substrate into the
      experimentally determined X-ray structure of substrate-free CYP2C8, which became
      available quite recently [Schoch, G. A., et al. (2004) J. Biol. Chem. 279, 9497],
      were consistent with key roles for S100, S114, and F205 residues in substrate
      binding. The results suggest that the effects of mutation of arginine 241 on
      anionic substrate hydroxylation could be indirect and result from alterations of
      the packing of helix G with helix B'.

PMID- 15581351
TI  - Structural perturbations in human ADP ribosylation factor-1 accompanying the
      binding of phosphatidylinositides.
AB  - ADP ribosylation factors (Arfs) are members of a family of Ras-related GTPases
      that regulate a wide variety of intracellular signaling pathways, including the
      regulation of membrane traffic and organelle morphology. Arfs perform these
      functions through interactions with Arf-specific guanine nucleotide exchange
      factors (GEFs), GTPase activating proteins (GAPs), and effectors. Signaling
      phosphatidylinositides, most commonly phosphatidylinositol (4,5)-bisphosphate
      (PI(4,5)P(2)) or phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P(3)), have
      been shown previously to regulate the activities of a number of these regulators
      and effectors of Arf. The ability of Arf itself to bind these same
      phosphatidylinositides also has been reported previously, though without much
      structural detail. We investigated the ability of human Arf1.GDP (Arf1.GDP) to
      bind myo-inositol (1,4,5)-trisphosphate (I(1,4,5)P(3)), the soluble headgroup for
      PI(4,5)P(2), and a short acyl-chain soluble PI(4,5)P(2) analogue using
      heteronuclear single quantum coherence (HSQC)-based NMR techniques. A patch of
      positive electrostatic potential on the surface of Arf1.GDP is identified as
      being directly involved in ligand binding, but structural and stability changes
      extending to the N-terminal helix and nucleotide-binding site of Arf1 are also
      documented. The identified binding site and the resultant structural changes are
      discussed in terms of a possible influence of phosphatidylinositides on the
      binding of Arf1 to Arf1-GEF and subsequent nucleotide release.

PMID- 15581352
TI  - The effect of F-actin on the relay helix position of myosin II, as revealed by
      tryptophan fluorescence, and its implications for mechanochemical coupling.
AB  - The fluorescence properties of Dictyostelium discoideum (Dd) myosin II constructs
      containing a single tryptophan residue have revealed detailed information
      regarding nucleotide binding and hydrolysis steps. Here we extend these studies
      to investigate the influence of actin on nucleotide-induced fluorescence
      transients. The fluorescence from native actin tryptophan residues is not
      significantly perturbed on binding to myosin, although an apparent signal is
      detected as a consequence of a light scatter artifact. Actin has a minor effect
      on the response of W129, located at the entrance to the nucleotide-binding
      pocket, and reduces the forward rate constants for the isomerization(s)
      associated with binding of ATP, ATPgammaS, and ADP by 3-fold or less. The
      isomerization detected by W129 clearly precedes the dissociation of actin in the
      case of ADP and ATPgammaS binding. The fluorescence from the conserved W501
      residue, located at the distal end of the relay helix, is very sensitive to the
      switch 2 and/or lever arm disposition. Consequently, the observed fluorescence
      emission intensity can be used to estimate the equilibrium constant between the
      pre- and post-power stroke conformations. Actin modulates this equilibrium by no
      more than 2-fold in the presence of nucleoside triphosphate. These data have
      implications for the mechanism of product release and suggest that actin
      activates another process in the mechanism, such as switch 1 movement and Pi
      release, rather than influencing the switch 2 equilibrium and lever arm position
      directly.

PMID- 15581353
TI  - Intrasteric inhibition mediates the interaction of the I/LWEQ module proteins
      Talin1, Talin2, Hip1, and Hip12 with actin.
AB  - The I/LWEQ module superfamily is a class of actin-binding proteins that contains
      a conserved C-terminal actin-binding element known as the I/LWEQ module. I/LWEQ
      module proteins include the metazoan talins, the cellular slime mold talin
      homologues TalA and TalB, fungal Sla2p, and the metazoan Sla2 homologues Hip1 and
      Hip12 (Hip1R). These proteins possess a similar modular organization that
      includes an I/LWEQ module at their C-termini and either a FERM domain or an ENTH
      domain at their N-termini. As a result of this modular organization, I/LWEQ
      module proteins may serve as linkers between cellular compartments, such as the
      plasma membrane and the endocytic machinery, and the actin cytoskeleton. Previous
      studies have shown that I/LWEQ module proteins bind to F-actin. In this report,
      we have determined the affinity of the I/LWEQ module proteins Talin1, Talin2,
      huntingtin interacting protein-1 (Hip1), and the Hip1-related protein
      (Hip1R/Hip12) for F-actin and identified a conserved structural element that
      interferes with the actin binding capacity of these proteins. Our data support
      the hypothesis that the actin-binding determinants in native talin and other
      I/LWEQ module proteins are cryptic and indicate that the actin binding capacities
      of Talin1, Talin2, Hip1, and Hip12 are regulated by intrasteric occlusion of
      primary actin-binding determinants within the I/LWEQ module. We have also found
      that the I/LWEQ module contains a dimerization motif and stabilizes actin
      filaments against depolymerization. This activity may contribute to the function
      of talin in cell adhesion and the roles of Hip1, Hip12 (Hip1R), and Sla2p in
      endocytosis.

PMID- 15581354
TI  - Recognition of an unnatural difluorophenyl nucleotide by uracil DNA glycosylase.
AB  - The DNA repair enzyme uracil DNA glycosylase (UDG) utilizes base flipping to
      recognize and remove unwanted uracil bases from the genome but does not react
      with its structural congener, thymine, which differs by a single methyl group.
      Two factors that determine whether an enzyme flips a base from the duplex are its
      shape and hydrogen bonding properties. To probe the role of these factors in
      uracil recognition by UDG, we have synthesized a DNA duplex that contains a
      single difluorophenyl (F) nucleotide analogue that is an excellent isostere of
      uracil but possesses no hydrogen bond donor or acceptor groups. By using binding
      affinity measurements, solution (19)F NMR, and solid state (31)P[(19)F]
      rotational-echo double-resonance (REDOR) NMR measurements, we establish that UDG
      partially unstacks F from the duplex. However, due to the lack of hydrogen
      bonding groups that are required to support an open-to-closed conformational
      transition in UDG, F cannot stably dock in the UDG active site. We propose that F
      attains a metastable unstacked state that mimics a previously detected
      intermediate on the uracil-flipping pathway and suggest structural models of the
      metastable state that are consistent with the REDOR NMR measurements.

PMID- 15581355
TI  - Molecular basis of the time-dependent inhibition of cyclooxygenases by
      indomethacin.
AB  - Cyclooxygenases (COXs) are the therapeutic targets of nonsteroidal
      antiinflammatory drugs. Indomethacin (INDO) was one of the first nonsteroidal
      antiinflammatory drugs to be characterized as a time-dependent, functionally
      irreversible inhibitor, but the molecular basis of this phenomenon is uncertain.
      In the crystal structure of INDO bound to COX-2, a small hydrophobic pocket was
      identified that surrounds the 2'-methyl group of INDO. The pocket is formed by
      the residues Ala-527, Val-349, Ser-530, and Leu-531. The contribution of this
      pocket to inhibition was evaluated by altering its volume by mutagenesis of Val
      349. The V349A mutation expanded the pocket and increased the potency of INDO,
      whereas the V349L mutation reduced the size of the pocket and decreased the
      potency of INDO. Particularly striking was the reversibility of INDO inhibition
      of the V349L mutant. The 2'-des-methyl analogue of INDO (DM-INDO) was synthesized
      and tested against wild-type COX-1 and COX-2, as well as the Val-349 mutants. DM
      INDO bound to all enzymes tested, but only inhibited wt mCOX-2 and the V349I
      enzyme. Without the 2'-methyl group anchoring DM-INDO in the active site, the
      compound was readily competed off of the enzyme by arachidonic acid. The kinetics
      of inhibition were comparable to the kinetics of binding as evaluated by
      fluorescence quenching. These results highlight binding of the 2'-methyl of INDO
      in the hydrophobic pocket as an important determinant of its time-dependent
      inhibition of COX enzymes.

PMID- 15581356
TI  - Synchronized conformational fluctuations and binding site desolvation during
      molecular recognition.
AB  - Binding site desolvation is a poorly understood prerequisite to ligand binding.
      Although structural fluctuations may be expected to have an important role,
      little is known about which fluctuations are important or the mechanism by which
      they promote desolvation. This investigation examines whether and how specific
      structural fluctuations contribute to desolvation of the ligand binding site in
      glycopeptide antibiotics. Backbone peptide group rotations in vancomycin, known
      to occur by experimental observation, were examined in this work with a two
      dimensional adaptive umbrella sampling molecular dynamics simulation technique.
      Results indicate that energetic barriers to rotation are relatively small for two
      of the peptide groups intimately involved in ligand recognition. When they occur,
      these rotations strip water molecules away from key hydrogen bond donors and
      simultaneously cause significant distortions in the macrocyclic rings of the
      antibiotic that force water into and out of the binding site. Both events are
      intricately synchronized on the molecular level and have consequences that are
      clearly necessary to prepare the binding site for receiving a ligand. These
      results suggest that previously reported observations concerning structural
      dynamics and binding kinetics in these compounds are mechanistically linked, and
      they illustrate a heretofore unrecognized degree of preorganization, complexity,
      and synchronization that may be involved in specific molecular recognition. They
      also suggest that strategies for increasing antibiotic affinity through covalent
      dimerization may be counterproductive.

PMID- 15581357
TI  - Improving the sensitivity and dynamic range of reagentless fluorescent
      immunosensors by knowledge-based design.
AB  - The variable fragment (Fv) of an antibody can be transformed into a reagentless
      fluorescent biosensor by mutating a residue into a cysteine in the neighborhood
      of the paratope (antigen-binding site) and then coupling an environment-sensitive
      fluorophore, e.g., N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3
      diazole (IANBD ester), to the mutant cysteine. For some residues, named
      operational, the formation of the conjugate does not affect the affinity of the
      Fv fragment for the antigen, and the binding of the antigen generates a
      measurable variation in the fluorescence intensity of the conjugate. We tested if
      this signal variation could be increased by coupling several molecules of
      fluorophores to the same molecule of Fv. Seven operational residues have been
      previously identified in the single-chain Fv (scFv) of monoclonal antibody D1.3
      (mAbD1.3), directed against lysozyme. Ten double mutants of scFvD1.3, involving
      these residues, were constructed and coupled to the IANBD ester. The fluorescence
      of the double conjugates revealed a transfer of resonance energy between the two
      identical fluorescent groups. This homotranfer could be more important in the
      free state of the conjugate than in its antigen-bound state and increase its
      sensitivity for the detection of the antigen by up to 2.9-fold. A poorly
      sensitive conjugate could be improved by coupling a second molecule of
      fluorophore to residues located far from the paratope. Mutations altering the
      affinity of scFvD1.3 for lysozyme were introduced into one of its fluorescent
      conjugates. Using a mixture of three mutant derivatives of this unique conjugate,
      we could titrate lysozyme with precision in a concentration range encompassing 3
      orders of magnitude.

PMID- 15581358
TI  - A soluble C1b protein and its regulation of soluble type 7 adenylyl cyclase.
AB  - Adenylyl cyclase (AC) is a prototypical cell-signaling molecule expressed in
      virtually all organisms from bacteria to man. While C1b, a poorly conserved
      region within mammalian AC, has been implicated in numerous isoform-specific
      regulatory properties, no one has purified the C1b region as a functional protein
      to homogeneity in order to study its role in enzyme function. We hypothesize that
      C1b is an internal regulatory subunit. To pursue this hypothesis, we constructed
      several soluble C1b proteins from type VII AC, arriving at one, 7C1b-S, which can
      be expressed and purified from Escherichia coli. 7C1b-S is relatively stable, as
      demonstrated by limited proteolytic analysis, circular dichroism, and UV Raman
      spectroscopy. Using size-exclusion chromatography and co-immunoprecipitation we
      demonstrate that 7C1b-S interacts with a cardinal activator of AC (Gsalpha) and
      with the conserved first catalytic domain (C1a) of type VII AC. We show that 7C1b
      S inhibits Gsalpha-stimulated and Gsalpha-forskolin stimulated activity in our
      soluble ACVII model system. On the basis of these results, we suggest that 7C1b-S
      meets basic criteria to serve as a model protein for the C1b region and may be
      used as a prototype to develop other isoform C1b soluble model proteins to
      further investigate the role of this domain in isoform-specific regulation of
      adenylyl cyclase.

PMID- 15581359
TI  - YfiT from Bacillus subtilis is a probable metal-dependent hydrolase with an
      unusual four-helix bundle topology.
AB  - YfiT, a 19-kDa polypeptide from Bacillus subtilis, belongs to a small sequence
      family with members predominantly from Gram positive bacteria. We have determined
      the crystal structure of YfiT in complex with Ni(2+) to a resolution of 1.7 A.
      YfiT exists as a dimer and binds Ni(2+) in a 1:1 stoichiometry. The protein has
      an unusual four-helix bundle topology and coordinates Ni(2+) in an octahedral
      geometry with three conserved histidines and three waters. Although there is no
      similarity in their overall structures, the coordination geometry of the metal
      and the residues that constitute the putative active site in YfiT are similar to
      those of metalloproteases such as thermolysin. Our structural analyses suggest
      that YfiT might function as a metal-dependent hydrolase.

PMID- 15581360
TI  - Multiple orientations in a physiological complex: the pyruvate-ferredoxin
      oxidoreductase-ferredoxin system.
AB  - Ferredoxin I from Desulfovibrio africanus (Da FdI) is a small acidic [4Fe-4S]
      cluster protein that exchanges electrons with pyruvate-ferredoxin oxidoreductase
      (PFOR), a key enzyme in the energy metabolism of anaerobes. The thermodynamic
      properties and the electron transfer between PFOR and either native or mutated
      FdI have been investigated by microcalorimetry and steady-state kinetics,
      respectively. The association constant of the PFOR-FdI complex is 3.85 x 10(5) M(
      1), and the binding affinity has been found to be highly sensitive to ionic
      strength, suggesting the involvement of electrostatic forces in formation of the
      complex. Surprisingly, the punctual or combined neutralizations of carboxylate
      residues surrounding the [4Fe-4S] cluster slightly affect the PFOR-FdI
      interaction. Furthermore, hydrophobic residues around the cluster do not seem to
      be crucial for the PFOR-FdI system activity; however, some of them play an
      important role in the stability of the FeS cluster. NMR restrained docking
      associated with site-directed mutagenesis studies suggested the presence of
      various interacting sites on Da FdI. The modification of additional acidic
      residues at the interacting interface, generating a FdI pentamutant, evidenced at
      least two distinct FdI binding sites facing the distal [4Fe-4S] cluster of the
      PFOR. We also used a set of various small acidic partners to investigate the
      specificity of PFOR toward redox partners. The remarkable flexibility of the PFOR
      FdI system supports the idea that the specificity of the physiological complex
      has probably been "sacrificed" to improve the turnover rate and thus the
      efficiency of bacterial electron transfer.

PMID- 15581361
TI  - Requirements for pYXXM motifs in Cbl for binding to the p85 subunit of
      phosphatidylinositol 3-kinase and Crk, and activation of atypical protein kinase
      C and glucose transport during insulin action in 3T3/L1 adipocytes.
AB  - Cbl is phosphorylated by the insulin receptor and reportedly functions within the
      flotillin/CAP/Cbl/Crk/C3G/TC10 complex during insulin-stimulated glucose
      transport in 3T3/L1 adipocytes. Cbl, via pYXXM motifs at tyrosine-371 and
      tyrosine-731, also activates phosphatidylinositol (PI) 3-kinase, which is
      required to activate atypical protein kinase C (aPKC) and glucose transport
      during thiazolidinedione action in 3T3/L1 and human adipocytes [Miura et al.
      (2003) Biochemistry 42, 14335-14341]. Presently, we have examined the importance
      of Cbl in activating PI 3-kinase and aPKC during insulin action in 3T3/L1
      adipocytes by expressing Y371F and Y731F Cbl mutants, which nullify pYXXM binding
      of Cbl to SH2 domains of downstream effectors. Interestingly, these mutants
      inhibited insulin-induced increases in (a) binding of Cbl to both Crk and the p85
      subunit of PI 3-kinase, (b) activation of Cbl-dependent PI 3-kinase, (c)
      activation and translocation of aPKC to the plasma membrane, (d) translocation of
      Glut4 to the plasma membrane, (e) and glucose transport. Importantly,
      coexpression of wild-type Cbl reversed the inhibitory effects of Cbl mutants. In
      contrast to Cbl-dependent PI 3-kinase, Cbl mutants did not significantly inhibit
      the activation of PI 3-kinase by IRS-1, which is also required during insulin
      action. Our findings suggest that (a) Cbl uses pYXXM motifs to simultaneously
      activate PI 3-kinase and Crk/C3G/TC10 pathways and (b) Cbl, along with IRS-1,
      functions upstream of PI 3-kinase and aPKCs during insulin-stimulated glucose
      transport in 3T3/L1 adipocytes.

PMID- 15581362
TI  - Insulin substrates 1 and 2 are corequired for activation of atypical protein
      kinase C and Cbl-dependent phosphatidylinositol 3-kinase during insulin action in
      immortalized brown adipocytes.
AB  - Phosphatidylinositol 3-kinase (PI3K)-dependent activation of atypical protein
      kinase C (aPKC) is required for insulin-stimulated glucose transport. Although
      insulin receptor substrate-1 (IRS-1) and IRS-2, among other factors, activate
      PI3K, there is little information on the relative roles of IRS-1and IRS-2 during
      aPKC activation by insulin action in specific cell types. Presently, we have used
      immortalized brown adipocytes in which either IRS-1 or IRS-2 has been knocked out
      by recombinant methods to examine IRS-1 and IRS-2 requirements for activation of
      aPKC. We have also used these adipocytes to see if IRS-1 and IRS-2 are required
      for activation of Cbl, which is required for insulin-stimulated glucose transport
      and has been found to function upstream of both PI3K/aPKC and Crk during
      thiazolidinedione action in 3T3/L1 adipocytes [Miura et al. (2003) Biochemistry
      42, 14335]. In brown adipocytes in which either IRS-1 or IRS-2 was knocked out,
      insulin-induced increases in aPKC activity and glucose transport were markedly
      diminished. These effects of insulin on aPKC and glucose transport were fully
      restored by retroviral-mediated expression of IRS-1 or IRS-2 in their respective
      knockout cells. Knockout of IRS-1 or IRS-2 also inhibited insulin-induced
      increases in Cbl binding to the p85 subunit of PI3K, which, along with IRS-1/2,
      may be required for activation of PI3K, aPKC, and glucose transport during
      insulin action in 3T3/L1 adipocytes. These findings provide evidence that
      directly links both IRS-1 and IRS-2 to aPKC activation in immortalized brown
      adipocytes, and further suggest that IRS-1 and IRS-2 are required for the
      activation of Cbl/PI3K during insulin action in these cells.

PMID- 15581363
TI  - Phosphorylation analysis of 90 kDa heat shock protein within the cytosolic
      arylhydrocarbon receptor complex.
AB  - The arylhydrocarbon receptor (AhR) functions as a ligand-activated transcription
      factor that regulates the transcription of genes encoding xenobiotic metabolizing
      enzymes and also mediates most of the toxic effects caused by dioxins and
      polycyclic aromatic hydrocarbons. The cytosolic AhR complex exists as a
      transcriptionally cryptic complex, consisting of the 90 kDa heat shock protein
      (HSP90) and the hepatitis B virus X-associated protein 2 (XAP2). The
      posttranslational modifications, especially phosphorylation, of the cytosolic AhR
      HSP90-XAP2 complex are poorly understood, although the phosphorylation of a
      transcriptionally active heterodimer of AhR and an AhR nuclear translocator is
      critically involved in AhR function. To reveal the phosphorylation status
      involved in AhR function, we used mass spectrometry to determine the site
      specific phosphorylation of the steady-state cytosolic AhR complex, prepared from
      Chinese hamster ovary cells stably expressing mouse AhR. We identified
      phosphorylations of the HSP90 subunits within the AhR complex at Ser225 and
      Ser254 of HSP90beta and Ser230 of HSP90alpha. By site-directed mutagenesis, these
      serine residues were substituted with alanine and glutamic acid to elucidate the
      role of the HSP90beta serine phosphorylations in the AhR function.
      Immunoprecipitation assays using COS7 transfectants showed that the replacement
      of Ser225 and Ser254 by Ala, S225/254A, increased the binding affinity for AhR,
      as compared with the Glu replacement. In a ligand-induced AhR transcription
      activity assay using Hepa1 transfectants, the S255/254A mutant exhibited more
      potent transcription activity than the S225/254E mutant, which had activity
      similar to that of wild-type HSP90beta. These results suggest that the
      phosphorylations in the charged linker region of the HSP90 molecule modulate the
      formation of the functional cytosolic AhR complex.

PMID- 15581364
TI  - Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping of an
      enethiolate intermediate with a mechanism-based inactivating agent.
AB  - Phosphopantothenoylcysteine decarboxylase (PPC-DC) catalyzes the decarboxylation
      of the cysteine moiety of 4'-phosphopantothenoylcysteine (PPC) to form 4'
      phosphopantetheine (PPantSH); this reaction forms part of the biosynthesis of
      coenzyme A. The enzyme is a member of the larger family of cysteine
      decarboxylases including the lantibiotic-biosynthesizing enzymes EpiD and MrsD,
      all of which use a tightly bound flavin cofactor to oxidize the thiol moiety of
      the substrate to a thioaldehyde. The thioaldehyde serves to delocalize the charge
      that develops in the subsequent decarboxylation reaction. In the case of PPC-DC
      enzymes the resulting enethiol is reduced to a thiol giving net decarboxylation
      of cysteine, while in EpiD and MrsD it is released as the final product of the
      reaction. In this paper, we describe the characterization of the novel
      cyclopropyl-substituted product analogue 4'-phospho-N-(1-mercaptomethyl
      cyclopropyl)-pantothenamide (PPanDeltaSH) as a mechanism-based inhibitor of the
      human PPC-DC enzyme. This inhibitor alkylates the enzyme on Cys(173), resulting
      in the trapping of a covalently bound enethiolate intermediate. When Cys(173) is
      exchanged for the weaker acid serine by site-directed mutagenesis the enethiolate
      reaction intermediate also accumulates. This suggests that Cys(173) serves as an
      active site acid in the protonation of the enethiolate intermediate in PPC-DC
      enzymes. We propose that this protonation step is the key mechanistic difference
      between the oxidative decarboxylases EpiD and MrsD (which have either serine or
      threonine at the corresponding position in their active sites) and PPC-DC
      enzymes, which also reduce the intermediate in an overall simple decarboxylation
      reaction.

PMID- 15581365
TI  - Chemical mechanism of the serine acetyltransferase from Haemophilus influenzae.
AB  - The pH dependence of kinetic parameters was determined in both reaction
      directions to obtain information about the acid-base chemical mechanism of serine
      acetyltransferase from Haemophilus influenzae (HiSAT). The maximum rates in both
      reaction directions, as well as the V/K(serine) and V/K(OAS), decrease at low pH,
      exhibiting a pK of approximately 7 for a single enzyme residue that must be
      unprotonated for optimum activity. The pH-independent values of V(1)/E(t),
      V(1)/K(serine)E(t), V/K(AcCoA)E(t), V(2)/E(t), V(2)/K(OAS)E(t), and V/K(CoA)E(t)
      are 3300 +/- 180 s(-1), (9.6 +/- 0.4) x 10(5) M(-1) s(-1), 3.3 x 10(6) M(-1) s(
      1), 420 +/- 50 s(-1), (2.1 +/- 0.5) x 10(4) M(-1) s(-1), and (4.2 +/- 0.7) x
      10(5) M(-1) s(-1), respectively. The K(i) values for the competitive inhibitors
      glycine and l-cysteine are pH-independent. The solvent deuterium kinetic isotope
      effects on V and V/K in the direction of serine acetylation are 1.9 +/- 0.2 and
      2.5 +/- 0.4, respectively, and the proton inventories are linear for both
      parameters. Data are consistent with a single proton in flight in the rate
      limiting transition state. A general base catalytic mechanism is proposed for the
      serine acetyltransferase. Once acetyl-CoA and l-serine are bound, an enzymic
      general base accepts a proton from the l-serine side chain hydroxyl as it
      undergoes a nucleophilic attack on the carbonyl of acetyl-CoA. The same enzyme
      residue then functions as a general acid, donating a proton to the sulfur atom of
      CoASH as the tetrahedral intermediate collapses, generating the products OAS and
      CoASH. The rate-limiting step in the reaction at limiting l-serine levels is
      likely formation of the tetrahedral intermediate between serine and acetyl-CoA.

PMID- 15581366
TI  - Enzymatic characterization of the streptococcal endopeptidase, IdeS, reveals that
      it is a cysteine protease with strict specificity for IgG cleavage due to exosite
      binding.
AB  - Streptococcus pyogenes, an important pathogen in humans, secretes an IgG specific
      endopeptidase named IdeS. To elucidate the mechanism that is responsible for this
      specificity, we have here characterized the activity of IdeS in detail. Both
      gamma chains of human IgG or its Fc fragment were cleaved in the hinge region
      after Gly236 by IdeS, but other proteins or synthetic peptides containing
      sequences such as the P(4)-P(1) segment in the IgG cleavage site, or long
      peptides resembling the IgG hinge, were not hydrolyzed at all. This is likely due
      to a second binding site interacting with the Fc part of IgG. The lack of IdeS
      activity on peptide substrates necessitated the development of an assay with IgG
      as the substrate for kinetic studies. IdeS showed a sigmoidal velocity curve at
      physiological IgG concentrations, and a declining enzyme rate at higher IgG
      concentrations. This atypical velocity curve suggests product inhibition and/or
      allosteric control, which again indicates the presence of an exosite involved in
      substrate binding. The pseudoequilibrium constant for IdeS hydrolysis of IgG was
      90 microM. The enzyme exhibited activity in the pH range of 5.1-7.6, with an
      optimum at pH 6.6. IdeS was stable above pH 10 but not at acidic pH. It exhibited
      an activity maximum around 37 degrees C and a decreased thermal stability at 42
      degrees C. Iodoacetate and iodoacetamide inhibited IdeS, as expected for a
      cysteine protease, and biochemical evidence verified this classification. E-64
      and chicken cystatin, specific inhibitors of family C1 and C13 cysteine
      proteases, were without effect on enzyme activity, as were class specific serine,
      aspartic, and metallo protease inhibitors. No significant similarities were found
      in protein sequence comparisons with known enzyme families, suggesting that IdeS
      represents a novel family of cysteine proteases.

PMID- 15581367
TI  - Effects of the antibiotic pulvomycin on the elongation factor Tu-dependent
      reactions. Comparison with other antibiotics.
AB  - The antibiotic pulvomycin is an inhibitor of protein synthesis that prevents the
      formation of the ternary complex between elongation factor (EF-) Tu.GTP and
      aminoacyl-tRNA. In this report, novel aspects of its action on EF-Tu are
      described. Pulvomycin markedly affects the equilibrium and kinetics of the EF-Tu
      nucleotide interaction, particularly of the EF-Tu.GTP complex. The binding
      affinity of EF-Tu for GTP is increased 1000 times, mainly as the consequence of a
      dramatic decrease in the dissociation rate of this complex. In contrast, the
      affinity for GDP is decreased 10-fold due to a marked increase in the
      dissociation rate of EF-Tu.GDP (25-fold) that mimics the action of EF-Ts, the
      GDP/GTP exchange factor of EF-Tu. The effects of pulvomycin and EF-Ts can coexist
      and are simply additive, supporting the conclusion that these two ligands
      interact with different sites of EF-Tu. This is further confirmed on native PAGE
      by the ability of EF-Tu to bind the EF-Ts and the antibiotic simultaneously.
      Pulvomycin enhances the intrinsic EF-Tu GTPase activity, like kirromycin, though
      to a much more modest extent. As with kirromycin, this stimulation depends on the
      concentration and nature of the monovalent cations, Li(+) being the most
      effective one, followed by Na(+), K(+), and NH(4)(+). In the presence of
      pulvomycin (in contrast to kirromycin), aa-tRNA and/or ribosomes do not enhance
      the GTPase activity of EF-Tu. The property of pulvomycin to modify selectively
      the conformation(s) of EF-Tu is also supported by its effect on heat- and urea
      dependent denaturation, and tryptic digestion of the protein. Specific
      differences and similarities between the action of pulvomycin and the other EF-Tu
      specific antibiotics are described and discussed.

PMID- 15581368
TI  - Similar mutagenicity of photoactivated porphyrins and ultraviolet A radiation in
      mouse embryonic fibroblasts: involvement of oxidative DNA lesions in mutagenesis.
AB  - Ultraviolet A (UVA) radiation is implicated in the etiology of human skin cancer.
      However, the underlying mechanism of carcinogenicity for UVA is not fully
      delineated. A mutagenic role for UVA has been suggested, which involves
      activation of endogenous photosensitizers generating oxidative DNA damage. We
      investigated the mutagenicity of UVA alone and in combination with delta
      aminolevulinic acid (delta-ALA), a precursor of the intracellular
      photosensitizers porphyrins, in transgenic Big Blue mouse embryonic fibroblasts.
      A significant generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a
      typical promutagenic oxidative DNA lesion, was observed in cells treated with a
      combination of delta-ALA (1 mM) and UVA (0.06 J/cm(2)) as quantified by high
      pressure liquid chromatography-tandem mass spectrometry (p < 0.001; relative to
      the control). The steady-state level of 8-oxo-dG, however, remained unchanged in
      cells irradiated with UVA or treated with delta-ALA alone. Other photolesions
      including cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone
      photoproducts were not detectable in cells treated with delta-ALA and/or
      irradiated with UVA as determined by terminal transferase-dependent polymerase
      chain reaction assay. Mutation analyses of the cII transgene in cells treated
      with a combination of delta-ALA and UVA showed an approximately 3-fold increase
      in mutant frequency relative to the control (p < 0.008), as well as a unique
      induced mutation spectrum as established by DNA sequence analysis (p < 0.005; 95%
      CI, 0.002-0.009). No mutagenic effects were observed in cells irradiated with UVA
      or treated with delta-ALA alone. The spectrum of mutations produced by delta-ALA
      plus UVA was characterized by a significantly increased frequency of G --> T
      transversions (p < 0.0003; relative to the control), which are the hallmark
      mutations induced by 8-oxo-dG. Notably, the 8-oxo-dG-mediated mutagenicity of UVA
      plus delta-ALA is similar to that established previously for UVA alone at a
      mutagenic dose of 18 J/cm(2). We conclude that, in the presence of exogenous
      photosensitizers, UVA at a nonmutagenic dose induces mutations through the same
      mechanism as does a mutagenic dose of UVA per se.

PMID- 15581369
TI  - Beta-elimination coupled with tandem mass spectrometry for the identification of
      in vivo and in vitro phosphorylation sites in maize dehydrin DHN1 protein.
AB  - Dehydrins are a group of proteins that are accumulated during environmental
      stress such as drought and low temperature or during late embryogenesis. In the
      present study, we isolated dehydrin DHN1, also known as Rab17 protein, from maize
      kernel by an acid extraction method, removed the phosphoric acid groups from
      phosphorylated residues by beta-elimination via treating the protein with barium
      hydroxide, and identified the sites of phosphorylation by tandem mass
      spectrometry. Our results showed that each of the seven contiguous serine
      residues (Ser78-Ser84) in the serine tract could be phosphorylated. The beta
      elimination procedure was shown to be essential for the detection and subsequent
      site mapping of the heavily phosphorylated peptide by mass spectrometry. We also
      found that protein kinase CK2 could catalyze the phosphorylation of the DHN1
      protein in vitro and the level of phosphorylation was comparable to that of the
      DHN1 isolated from maize seeds. Moreover, the in vitro phosphorylation also
      occurred on the serine residues in the serine tract region, suggesting that CK2
      might be involved in the phosphorylation of the serine track region in maize
      kernel in vivo.

PMID- 15581370
TI  - Characterization of inward-rectifier K+ channel inhibition by antiarrhythmic
      piperazine.
AB  - Strong inward-rectifier K(+) (Kir) channels play a significant role in shaping
      the cardiac action potential: they help produce its long plateau and accelerate
      its rate of repolarization. Consequently, genetic deletion of the gene encoding
      the strongly rectifying K(+) channel IRK1 (Kir2.1) prolongs the cardiac action
      potential in mice. In principle, broadening the action potential lengthens the
      refractory period, which may in turn be antiarrhythmogenic. Interestingly,
      previous studies showed that piperazine, an inexpensive and safe anthelmintic,
      both inhibits IRK1 channels and is antiarrhythmic in some animal preparations.
      This potential pharmacological benefit motivated us to further characterize the
      energetic, kinetic, and molecular properties of IRK1 inhibition by piperazine. We
      show how its blocking characteristics, in particular, its shallow voltage
      dependence, allow piperazine to be effective even in the presence of high
      affinity polyamine blockers. We also examine the channel selectivity of
      piperazine and its molecular determinants.

PMID- 15581371
TI  - Caloric restriction results in phospholipid depletion, membrane remodeling, and
      triacylglycerol accumulation in murine myocardium.
AB  - Herein, we utilize the power of shotgun lipidomics to demonstrate that modest
      caloric restriction results in phospholipid depletion, membrane remodeling, and
      triacylglycerol (TAG) accumulation in murine myocardium. After brief periods of
      fasting (4 and 12 h), substantial decreases occurred in the choline and
      ethanolamine glycerophospholipid pools in murine myocardium (collectively, a
      decrease of 39 nmol of phospholipid per milligram of protein at 12 h representing
      approximately 25% of total phospholipid mass and approximately 20 cal of Gibbs
      free energy per gram wet weight of tissue). Remarkably, the selective loss of
      long-chain polyunsaturated molecular species was present in the major
      phospholipid classes thereby altering the physical properties of myocardial
      membranes. No decrease in TAG mass was present in myocardium during fasting, but
      rather myocardial TAG increased during 12 h of refeeding nearly 3-fold returning
      to baseline levels only after 24 h of refeeding. No alterations in other examined
      lipid classes were present during fasting. In contrast to these lipid alterations
      in myocardium, no decreases in phospholipid mass were present in skeletal muscle
      myocytes and a dramatic decrease in skeletal muscle (or skeletal muscle
      associated) TAG mass was prominent after 12 h of fasting. These results identify
      phospholipids as a rapidly mobilizable energy source during modest caloric
      deprivation in murine myocardium, while triacylglycerols are a major source of
      energy reserve in skeletal muscle. Collectively, these results demonstrate
      dramatic alterations in the membrane composition of mildly fasted mammalian
      myocardium that identify the unanticipated plasticity of myocardial phospholipids
      to adapt to modest chemical and physical perturbations.

PMID- 15581372
TI  - The intermediate chain of cytoplasmic dynein is partially disordered and gains
      structure upon binding to light-chain LC8.
AB  - The N-terminal domain of dynein intermediate chain, IC(1-289), is highly
      disordered, but upon binding to dynein light-chain LC8, it undergoes a
      significant conformational change to a more ordered structure. Using circular
      dichroism and fluorescence spectroscopy, we demonstrate that the change in
      conformation is due to an increase in the helical structure and to enhanced
      compactness in the environment of tryptophan 161. An increase in helical
      structure and compactness is also observed with trimethylamine-N-oxide (TMAO), a
      naturally occurring osmolyte used here as a probe to identify regions with a
      propensity for induced folding. Global protection of IC(1-289) from protease
      digestion upon LC8 binding was localized to a segment that includes residues
      downstream of the LC8-binding site. Several smaller constructs of IC(1-289)
      containing the LC8-binding site and one of the predicted helix or coiled-coil
      segments were made. IC(1-143) shows no increase in helical structure upon
      binding, while IC(114-260) shows an increase in helical structure similar to what
      is observed with IC(1-289). Binding of IC(114-260) to LC8 was monitored by
      fluorescence and native gel electrophoresis and shows saturation of binding, a
      stoichiometry of 1:1, and moderate binding affinity. The induced folding of IC(1
      289) upon LC8 binding suggests that LC8 could act through the intermediate chain
      to facilitate dynein assembly or regulate cargo-binding interactions.

PMID- 15581373
TI  - The early steps in the unfolding of azurin.
AB  - High-temperature molecular dynamics simulations were used to gain insight into
      the early steps in the unfolding pathway of azurin, a blue copper protein with a
      beta-barrel structure formed by two sheets arranged in a Greek key folding
      topology. The results reveal that unfolding of the beta-barrel in azurin is
      associated with dislocation of its unique alpha-helix with respect to the protein
      scaffold. Exposure of the hydrophobic core to solvent precedes complete
      disruption of secondary and tertiary structure, and modifications in the region
      around the active site are directly connected with this event. Denaturation of
      the protein initiates from the sheet coordinating the copper ion, and the other
      sheet maintains its topology. Results derived from the simulation were compared
      with experimental data obtained with different techniques, showing excellent
      agreement and providing a framework to understand the process of disruption and
      formation of the beta-barrel in azurin.

PMID- 15581374
TI  - Membrane translocation mechanism of the antimicrobial peptide buforin 2.
AB  - The antimicrobial peptide magainin 2 isolated from the skin of the African clawed
      frog Xenopus laevis crosses lipid bilayers by transiently forming a peptide-lipid
      supramolecular complex pore inducing membrane permeabilization and flip-flop of
      membrane lipids [Matsuzaki, K., Murase, O., Fujii, N., and Miyajima, K. (1996)
      Biochemistry 35, 11361-11368]. In contrast, the antimicrobial peptide buforin 2
      discovered in the stomach tissue of the Asian toad Bufo bufo gargarizans
      efficiently crosses lipid bilayers without inducing severe membrane
      permeabilization or lipid flip-flop, and the Pro(11) residue plays a key role in
      this unique property [Kobayashi, S, Takeshima, K., Park, C. B., Kim, S. C., and
      Matsuzaki, K. (2000) Biochemistry 39, 8648-8654]. To elucidate the translocation
      mechanism, the secondary structure and the orientation of the peptide in lipid
      bilayers as well as the effects of the peptide concentration, the lipid
      composition, and the cis-trans isomerization of the Pro peptide bond on
      translocation efficiency were investigated. The translocation efficiencies of
      F10W-buforin 2 (BF2), P11A-BF2, and F5W-magainin 2 (MG2) across egg yolk L-alpha
      phosphatidyl-DL-glycerol (EYPG)/egg yolk L-alpha-phosphatidylcholine (1/1)
      bilayers were dependent supralinearly on the peptide concentration, suggesting
      that the translocation mechanisms of these peptides are similar. The
      incorporation of the negative curvature-inducing lipid egg yolk L-alpha 
      phosphatidylethanolamine completely suppressed the translocation of BF2,
      indicating the induction of the positive curvature by BF2 on the membrane is
      related to the translocation process, similarly to MG2. In pure EYPG, where the
      repulsion between polycationic BF2 molecules is reduced, membrane
      permeabilization and coupling lipid flip-flop were clearly observed. Structural
      studies by use of Fourier transform infrared-polarized attenuated total
      reflection spectroscopy indicated that BF2 assumed distorted helical structures
      in EYPG/EYPC bilayers. A BF2 analogue with an alpha-methylproline, which fixed
      the peptide bond to the trans configuration, translocated similarly to the parent
      peptide, suggesting the cis-trans isomerization of the Pro peptide bond is not
      involved in the translocation process. These results indicate that BF2 crosses
      lipid bilayers via a mechanism similar to that of MG2. The presence of Pro(11)
      distorts the helix, concentrating basic amino acid residues in a limited
      amphipathic region, thus destabilizing the pore by enhanced electrostatic
      repulsion, enabling efficient translocation.

PMID- 15581375
TI  - pKa and aggregation of bilirubin: titrimetric and ultracentrifugation studies on
      water-soluble pegylated conjugates of bilirubin and fatty acids.
AB  - A water-soluble conjugate (1) with intact carboxyl groups was prepared by
      addition of poly(ethylene glycol) thiol (MPEG-SH) regiospecifically to the exo
      vinyl group of bilirubin. (1)H and (13)C NMR and absorbance spectroscopy in
      CDCl(3) and DMSO-d(6) confirmed the assigned structure and showed that pegylation
      did not disrupt the hydrogen-bonded ridge-tile conformation of the pigment
      moiety. Aqueous solutions of 1 were optically clear, but NMR signals were seen
      only from the MPEG portion and none from the tetrapyrrole, consistent with
      dissolved assemblies containing aggregated bilirubin cores within mobile
      polyether chains. On alkalinization (pH >12), signals from the pigment moiety
      reappeared. Titrimetric measurements on 1 in water showed the pK(a)'s of the two
      carboxyl groups to be similar (average 6.42). Control studies with pegylated half
      esters of succinic, suberic, brassylic, thapsic, and 1,20-eicosanedioic acid
      showed that pegylation per se has little, if any, effect on carboxyl ionization.
      However, aggregation increases the apparent pK(a) by approximately 1-2 units. The
      molecularity of bilirubin in solution was further characterized by
      ultracentrifugation. Over the pH range 8.5-10 in buffer, bilirubin formed
      multimers with aggregation numbers ranging from approximately 2-7. Bilirubin is
      monomeric in DMSO or CHCl(3) at approximately 2 x 10(-)(5) M, but aggregation
      occurred when the CHCl(3) was contaminated with trace adventitious (perhaps
      lipoidal) impurities. These observations show that aggregation increases the
      pK(a)'s of aliphatic carboxylic acids relative to their monomer values in water.
      They are consistent with earlier (13)C NMR-based estimates of approximately 4.2
      and approximately 4.9 for the aqueous pK(a)'s of bilirubin and similar studies of
      bilirubin in micellar bile-salt solutions. Together with earlier work, they
      confirm that the pK(a)'s of bilirubin are about normal for aliphatic carboxyls
      and suggest that the high (>7.5) values occasionally reported, including those
      based on CHCl(3) partitioning, are artifacts of aggregation or technique.

PMID- 15581376
TI  - Alpha-glucan recognition by a new family of carbohydrate-binding modules found
      primarily in bacterial pathogens.
AB  - TmPul13, a family 13 glycoside hydrolase from Thermotoga maritima, is a four
      module protein having pullulanase activity; the three N-terminal modules are of
      unknown function while the large C-terminal module is likely the catalytic
      module. Dissection of the functions of the three unknown modules revealed that
      the 100 amino acid module at the extreme N-terminus of TmPul13 comprises a new
      family of carbohydrate-binding modules (CBM) that a bioinformatic analysis shows
      are most frequently found in pullulanase-like sequences from bacterial pathogens.
      Detailed binding studies of this isolated CBM, here called TmCBM41, reveals a
      preference for alpha-(1,4)-linked glucans, but occasional alpha-(1,6)-linked
      glucose residues, such as those found in pullulan, are tolerated. UV difference,
      isothermal titration calorimetry, and analytical ultracentrifugation binding
      studies suggest that maltooligosaccharides longer than four glucose residues are
      able to bind two TmCBM41 molecules per oligosaccharide when sugar concentrations
      are below the CBM concentration. This is explained in terms of an equilibrium
      expression involving the formation of both a 1 to 1 sugar to CBM complex and a 1
      to 2 sugar to CBM complex (i.e., a CBM dimer ligated by an oligosaccharide). The
      presence of an alpha-(1-6) linkage in the oligosaccharide appears to prevent this
      phenomenon.

PMID- 15581378
TI  - Interferons in relapsing-remitting multiple sclerosis: are there benefits from
      long-term use?
AB  - Multiple sclerosis (MS) is one of the most common chronic neurological diseases
      in young adults in western countries. An important aspect of treatment of this
      disease is the use of interferons (IFNs). These are molecules with antiviral,
      immunomodulatory, antiproliferative and hormonal activities. IFNbeta, a class I
      IFN, has been used extensively in the therapy of MS, particularly in its
      relapsing-remitting (RRMS) phase, the most frequent clinical form of the disease.
      Although the available evidence from published clinical trials is difficult to
      evaluate because of methodological differences, an unbiased review of the data
      reveals sufficient evidence to conclude that treatment with IFNbeta in RRMS is
      both efficacious and safe, at least over the periods so far investigated (up to 4
      6 years). While there is no reason to suspect that IFNbeta should not continue to
      be efficacious and safe over the longer term, studies investigating these
      questions over longer periods and including greater numbers of patients are
      needed.

PMID- 15581379
TI  - Nitrone-related therapeutics: potential of NXY-059 for the treatment of acute
      ischaemic stroke.
AB  - At present, none of the neurodegenerative diseases such as Parkinson's disease,
      Alzheimer's disease and stroke are treatable with compounds that slow or halt
      neuronal cell death. However, the prototype nitrone radical trap alpha-phenyl
      tert-butylnitrone (PBN) has been shown to be an effective neuroprotective agent
      in various models of neurodegeneration. Some of these data are briefly reviewed
      as an introduction to an examination of the effect of the novel nitrone radical
      trapping agent disodium 2,4-disulfophenyl-N-tert-butylnitrone (NXY-059) in
      various animal models of stroke. NXY-059 has been shown to be an effective
      neuroprotective agent in both transient (reperfusion) and permanent focal
      ischaemia models in rats. In both types of model, NXY-059 has a large window of
      opportunity, providing effective neuroprotection when given up to 5 hours after
      the start of the occlusion in transient ischaemia and 4 hours after the start of
      permanent ischaemia. The compound is also effective in a marmoset permanent
      ischaemia model when administered up to 4 hours after the start of the occlusion.
      In this model it has been found to attenuate the problem of spatial neglect and
      maintain function to the paretic arm. NXY-059 administration also improves motor
      function in a rat haemorrhagic stroke model and has a neuroprotective effect in a
      rabbit thromboembolic stroke model. The compound is also well tolerated in stroke
      patients at plasma levels shown to provide a maximum neuroprotective effect in
      animal models of stroke.NXY-059, like PBN, is a nitrone with free radical
      trapping properties and this may be the basis of its neuroprotective action.
      However, experiments with PBN and NXY-059 suggest the possibility of other
      mechanisms being involved and these are also reviewed. Further experiments are
      required to fully elucidate the mechanism of action of these very effective
      neuroprotective agents.

PMID- 15581380
TI  - Remifentanil update: clinical science and utility.
AB  - The anilidopiperidine opioid remifentanil has pharmacodynamic properties similar
      to all opioids; however, its pharmacokinetic characteristics are unique.
      Favourable pharmacokinetic properties, minimally altered by extremes of age or
      renal or hepatic dysfunction, enable easy titration and rapid dissipation of
      clinical effect of this agent, even after prolonged infusion. Remifentanil is
      metabolised by esterases that are widespread throughout the plasma, red blood
      cells, and interstitial tissues, whereas other anilidopiperidine opioids (e.g.
      fentanyl, alfentanil and sufentanil) depend upon hepatic biotransformation and
      renal excretion for elimination. Consequently, remifentanil is cleared
      considerably more rapidly than other anilidopiperidine opioids. In addition, its
      pKa (the pH at which the drug is 50% ionised) is less than physiological pH;
      thus, remifentanil circulates primarily in the non-ionised moiety, which quickly
      penetrates the lipid blood-brain barrier and rapidly equilibrates across the
      plasma/effect site interface. By virtue of these distinctive pharmacokinetic
      properties, the context-sensitive half-time (i.e. the time required for the
      drug's plasma concentration to decrease by 50% after cessation of an infusion) of
      remifentanil remains consistently short (3.2 minutes), even following an infusion
      of long duration (> or =8 hours). Remifentanil, a clinically versatile opioid, is
      useful for intravenous analgesia and sedation in spontaneously breathing patients
      undergoing painful procedures. Profound analgesia may be achieved with minimal
      effect on cognitive function. Remifentanil may also provide sedation and
      analgesia during placement of regional anaesthetic blocks, and in conjunction
      with topical anaesthesia and airway nerve blocks, it may be useful for blunting
      reflex responses and facilitating 'awake' fibreoptic intubation. Compared with
      fentanyl and alfentanil in a day-surgery setting, remifentanil supplementation of
      general anaesthesia may improve intraoperative haemodynamic control. Both
      emergence time and the incidence of respiratory depression during post
      anaesthetic recovery may be reduced. However, outcomes such as home discharge
      time, post-emergence adverse effect profile, and patient and provider
      satisfaction are not significantly improved, and the incidence of intraoperative
      hypotension and bradycardia is greater. In addition, drug acquisition costs for
      remifentanil are higher and clinicians may need extra time to familiarise
      themselves with the drug's unique pharmacokinetics.Ironically, the quick
      dissipation of opioid analgesic effect following remifentanil discontinuation may
      be a significant clinical disadvantage. Unless little or no postoperative pain is
      anticipated, the clinician may wish to treat prospectively using local or
      regional anaesthesia, non-opioid analgesics, or longer-acting opioid analgesics.

PMID- 15581382
TI  - Antidepressant treatment and risk of suicide attempt by adolescents with major
      depressive disorder: a propensity-adjusted retrospective cohort study.
AB  - CONTEXT: The US FDA has issued an advisory warning of a possible link between
      antidepressant treatment for paediatric patients with major depressive disorder
      (MDD) and an increased risk of suicidal behaviour. A large database of paid
      health insurance claims for adolescents with MDD provided the opportunity to
      examine this possible relationship. OBJECTIVE: To examine the potential empirical
      link between antidepressant treatment and suicide attempts among adolescents aged
      12-18 years using a community sample of managed care enrollees across the US.
      DESIGN: A retrospective longitudinal cohort using paid insurance claims for all
      healthcare and prescription fills for adolescents who were newly diagnosed with
      MDD and had at least 6 months of follow-up data. A multivariate Cox proportional
      hazards regression analysis was used to test the hypothesis that antidepressant
      use increased the risk of suicide attempt, adjusting for propensity for
      allocation to each treatment group and for demographic and clinical
      characteristics. SETTING: Managed care plans including both commercial and
      Medicaid plans in the east, midwest, south and western regions of the US from
      January 1997 to March 2003. PARTICIPANTS: All adolescent insurance members aged
      12-18 years at first diagnosis of MDD. MAIN OUTCOME MEASURES: Suicide attempts as
      indicated by medical utilisation with International Classification of Diseases
      (9th edition) [ICD-9] or 10th edition (ICD-10) codes in any healthcare setting or
      by any covered provider. RESULTS: 24 119 adolescents met inclusion criteria (63%
      female). Crude suicide attempt rates ranged from 0.0-2.3% by index treatment
      group. Treatment with SSRIs (hazard ratio) [HR] = 1.59; CI 0.89, 2.82), other
      antidepressants (HR = 1.03; CI 0.43, 2.44), or multiple antidepressants (HR =
      1.43; CI 0.70, 2.89) after index MDD diagnosis resulted in no statistically
      increased risk of suicide attempt. Treatment with antidepressant medication for
      at least 180 days (6 months) reduced the likelihood of suicide attempt compared
      with antidepressant treatment for <55 days (8 weeks) [HR = 0.34; CI 0.21, 0.55].
      Other variables that were independently associated with greater risk of suicide
      attempts included female gender, severity of illness indicators, younger age at
      time of MDD diagnosis, and living in the midwest or west. CONCLUSIONS:
      Antidepressant medication use had no statistically significant effect on the
      likelihood of suicide attempt in a large cohort of adolescents across the US
      after propensity adjustment for treatment allocation and controlling for other
      factors. The relationship between suicidal behaviour and antidepressant
      medication use is complex and requires further investigation.

PMID- 15581383
TI  - Acute treatment of migraine with zolmitriptan 5 mg orally disintegrating tablet.
AB  - OBJECTIVE: To determine the speed of onset of headache response and duration of
      response with zolmitriptan 5 mg orally disintegrating tablet (ODT) in the acute
      treatment of migraine. BACKGROUND: Rapid pain relief is important for migraine
      sufferers. The early efficacy (30 minutes) of the 5 mg dose of the zolmitriptan
      ODT formulation was evaluated. METHODS: In this double-blind, parallel-group
      trial, 670 patients were randomised to receive either zolmitriptan 5 mg ODT
      (n=329) or matching placebo (n=341) to treat two migraine headaches of moderate
      or severe intensity. RESULTS: Zolmitriptan 5 mg ODT was significantly more
      effective than placebo in achieving a headache response (reduction in migraine
      headache intensity from moderate or severe to mild or no pain) at 30 minutes
      (16.5% vs 12.5%; p=0.048; primary endpoint), 1 hour (p <0.0001), and 2 hours (p
      <0.0001). Significantly more patients achieved a sustained headache response for
      24 hours with zolmitriptan 5 mg ODT than with placebo (42.5% vs 16.4%; p
      <0.0001). Zolmitriptan 5 mg ODT also produced a higher pain-free rate than
      placebo at all timepoints (0.5, 1 and 2 hours post-dose), with the differences
      becoming significant at 1 hour. Adverse events were reported by 37.7% of the
      patients treated with zolmitriptan 5 mg ODT and 18.1% of the patients treated
      with placebo. Those that occurred most often for the patients treated with
      zolmitriptan 5 mg ODT were tightness (7.0%), dizziness (6.7%), somnolence (6.7%)
      and paraesthesias (6.1%). CONCLUSIONS: A significant headache response as early
      as 30 minutes post-dose and good maintenance of this headache response at 24
      hours makes zolmitriptan 5 mg ODT an excellent acute treatment for migraine.
      Together with the relatively low adverse event rate, these data demonstrate that
      zolmitriptan 5 mg ODT is a valuable therapy for migraine sufferers.

PMID- 15581381
TI  - Role of the serotonergic system in the neurobiology of alcoholism: implications
      for treatment.
AB  - Preclinical studies have contributed greatly to our understanding of the
      neurochemical pathways associated with the development and maintenance of alcohol
      seeking behaviour. These studies have demonstrated the important role of
      serotonin pathways, particularly as they relate to dopaminergic function, which
      mediates alcohol-induced reward associated with its abuse liability. Naturally,
      this has led to the study of serotonergic agents as treatments for
      alcoholism.SSRIs do not appear to be effective treatment for a heterogeneous
      alcoholic group. However, they may be useful as treatment for late-onset
      alcoholics, or alcoholism complicated by comorbid major depression. Buspirone, a
      serotonin 5-HT1A partial agonist, does not appear to be an effective treatment
      for alcoholics without comorbid disease. Buspirone may, however, have some
      utility for treating alcoholics with comorbid anxiety disorder. The 5-HT2
      antagonist ritanserin, at pharmacologically relevant clinical doses, does not
      appear to be an effective treatment for alcoholism. Ondansetron, a 5-HT3
      antagonist, is an efficacious and promising medication for the treatment of early
      onset alcoholism. Preliminary evidence suggests that combining the mu antagonist
      naltrexone with the 5-HT3 antagonist ondansetron promises to be more effective
      for treating alcoholism than either alone. The differential treatment effect of
      SSRIs and ondansetron among various subtypes of alcoholic is intriguing. Future
      research is needed to understand more clearly the molecular genetic differences
      and the interactions of such differences with the environment that typify a
      particular alcoholic subtype. Such an understanding could enable us to make
      comfortable predictions as to which alcoholic subtype might respond best to a
      particular serotonergic agent, which could then be provided.

PMID- 15581384
TI  - Impact of rivastigmine use on the risk of nursing home placement in a US sample.
AB  - INTRODUCTION: Although numerous studies have evaluated predictors of nursing home
      placement (NHP), few have focused on the effects of cholinesterase inhibitor
      (ChEI) use on NHP. The objective of this study was to compare the risk of NHP
      between rivastigmine patients versus no-ChEI patients (control group), and
      secondly, between rivastigmine versus donepezil patients. METHODS: A
      retrospective analysis of a large US medical claims database was performed.
      Eligible subjects were identified from those who had continuous medical coverage
      from 1 April 2000 to 30 June 2002. Rivastigmine and donepezil subjects were new
      users, defined as having received no ChEI treatment during the initial 6 months
      of the study. Control subjects were diagnosed with Alzheimer's disease (AD) at
      some point after the initial 6-month period. All subjects were followed from
      baseline (initiation of ChEI therapy or initial AD diagnosis) to the date of NHP
      or 30 June 2002, whichever occurred first. RESULTS: In the rivastigmine (n=1181),
      donepezil (n=3864), and control (n=517) groups, 3.7%, 4.4% and 11.0% of subjects,
      respectively, had an NHP (p <0.001 for rivastigmine versus control). A Cox
      proportional hazard model, controlling for age, gender, comorbidities and
      behavioural disorders, showed that the control subjects were almost 3-fold more
      likely to have NHP than rivastigmine subjects (hazard ratio [HR]=2.71; 95% CI
      1.82, 4.03). The difference in the risk of NHP was not significant between the
      rivastigmine and donepezil groups (HR=1.23; 95% CI 0.89, 1.71). DISCUSSION: This
      study demonstrated that rivastigmine decreased the risk of NHP in a large insured
      population.

PMID- 15581385
TI  - The PROMISE study: PROphylaxis of MIgraine with SEglor (dihydroergotamine
      mesilate) in French primary care.
AB  - INTRODUCTION: Seglor capsules, a unique modified-release formulation of
      dihydroergotamine mesilate, have long been in clinical use in France for migraine
      prophylaxis. The aim of the PROMISE (PROphylaxis of MIgraine with SEglor) study
      was to establish the efficacy and tolerability of Seglor in the prevention of
      migraine in a general practice setting. METHODS: The PROMISE study was a double
      blind, placebo-controlled, parallel-group study carried out in primary care
      practice. It included 363 migraine patients treated with Seglor or placebo for 5
      months after a 1-month placebo run-in phase. RESULTS: Migraine attack frequency
      (primary efficacy criterion) decreased markedly in the two treatment groups so
      that the difference in favour of Seglor did not reach statistical significance.
      However, most secondary outcome measures (duration of single attack, total
      duration of attacks over 1 month, consumption of mild opiate analgesics,
      subjective improvement) improved to a significantly greater degree in patients
      receiving Seglor than in those receiving placebo. In the 84.5% of patients who
      had impaired quality of life at entry, the percentage of reduction in attack
      frequency and most other efficacy measures showed significant improvement with
      Seglor. The safety profile for Seglor was comparable to that of placebo.
      CONCLUSION: These results support the effectiveness of Seglor in patients with
      migraine-related quality-of-life impairment. The findings of the PROMISE study
      also suggest that patients' quality of life should be assessed systematically
      before initiating a preventive treatment for migraine.

PMID- 15581386
TI  - Zotepine for behavioural and psychological symptoms in dementia: an open-label
      study.

PMID- 15581387
TI  - Time-resolved microscopy of chromatin in vitro and in vivo.
AB  - In eukaryotic cell nuclei, double-stranded DNA is found in the form of chromatin,
      a large fiber made up of DNA complexed to histone proteins. In this article,
      recent studies using fluorescence techniques to look at the dynamics of
      chromatin, both in vivo and in vitro, are reviewed. Two-photon counterpropagating
      fluorescence recovery after patterned photobleaching is used to examine chromatin
      fluctuations on lengthscales ranging from less than 100 nm to microns. By
      combining in vivo studies with data on isolated nuclei and by measuring how these
      fluctuations depend on variables like ionic strength and photochemical cross
      linking, it is demonstrated that the relatively large-scale motions of chromatin
      observed in vivo are consistent with smaller scale modifications of the histone
      DNA interaction. This connection may provide a means to use conformational
      dynamics as an in vivo probe of the biochemical events involved in gene
      expression.

PMID- 15581388
TI  - UV exposure of elementary school children in five Japanese cities.
AB  - A 1 week UV-exposure measurement and outdoor-activity pattern survey was
      conducted for elementary school children for four seasons at five sites in Japan,
      i.e. Sapporo (43 degrees 05' N, altitude 40 m), Tsukuba (36 degrees 05' N, 20 m),
      Tokyo (35 degrees 40' N, 45 m), Miyazaki (31 degrees 60' N, 40 m) and Naha (26
      degrees 10' N, 5 m), and UV exposure was measured directly and estimated using
      outdoor-activity records. The study site with largest UV exposure was Miyazaki, a
      southern rural area. Comparing the results for boys and girls, UV exposure was
      larger in boys. UV exposure was large in spring and summer and small in winter.
      The total amount of UV exposure in spring and summer contributed 57.7-73.4% of
      total exposure for the year. As a whole, 8.1% and 1.8% of the schoolchildren were
      exposed to more than 1 minimum erythemal dose (MED) and 2 MED of solar UV in a
      day, respectively. The estimated yearly UV exposure ranged from 49 207 J/m2 in
      Miyazaki to 31 520 J/m2 in Tsukuba. The actual UV exposure correlated to
      potential UV exposure, estimated using outdoor-activity records and ambient UV
      irradiance, but the ratio differed by season and site. The yearly average of
      percent UV exposure to ambient UV on a horizontal plane ranged from 9.9% in Tokyo
      to 4.0% in Naha. In the questionnaire survey on outdoor-activity pattern, a short
      question "How long did you spend time outdoors between 0900 and 1500 h?" gives
      the best estimates of UV exposure.

PMID- 15581389
TI  - The effect of pH on the topography of porphyrins in lipid membranes.
AB  - The effect of the acidity of the environment on the topography and photophysics
      of sensitizer molecules in homogeneous solutions, and when embedded in a lipid
      microenvironment, was studied. Four hematoporphyrin (HP) analogs were studied,
      which have chemical "spacers" of varying lengths between the chromophoric
      tetrapyrrole and the carboxylate moiety. These derivatives have essentially the
      same chemical attributes and reactivity as the parent compound, HP IX, which is
      used in clinical procedures of photodynamic therapy. The binding constants of
      these HP derivatives to membrane model systems increase with the length of
      carboxylate chain in the pH range 3.0-6.6. This effect of chain length is
      attributed to an increase in the hydrophobicity of the molecule on elongation of
      the alkyl chains. A strong pH dependence of the quenching efficiency of the
      porphyrins' fluorescence by iodide ions was observed in aqueous solution and is
      attributed to a unique electrostatic interaction between the fluorophore and the
      quencher. The quenching efficiency in liposomes, relative to the quenching in
      buffer, as a function of pH, shows that porphyrins in the neutral form penetrate
      deeper inside the lipid bilayer and are less exposed to external quenching than
      when negatively charged at the carboxylic moiety. This vertical displacement in
      the membrane is also evidenced in the effect of pH on the photosensitized
      oxidation efficiency of a membrane-bound chemical target. Increasing the pH
      causes a significant decrease in the sensitization efficiency in liposomes. This
      trend is attributed to the vertical localization, and protonation of the
      carboxylic groups on lowering the pH leads to sinking of the sensitizer into the
      lipid bilayer and to a consequent generation of singlet oxygen at a deeper point.
      This increases the dwell time of singlet oxygen within the bilayer, which results
      in greater photodamage to a membrane-residing singlet oxygen target.

PMID- 15581390
TI  - Evidence-based guidelines for the management of Lyme disease.
AB  - This report, completed in November 2003, is intended to serve as a resource for
      physicians, public health officials and organizations involved in the evaluation
      and treatment of Lyme disease.

PMID- 15581392
TI  - Regulation of lymphoid cell apoptosis by Jaks and Stats.
AB  - Regulation of T- and B-lymphocyte survival and death is crucial for maintaining
      immune homeostasis. Unresponsiveness to death signals can result in
      lymphoproliferative disorders including cancer and autoimmunity, whereas
      lymphocytes hypersensitive to such signals can be manifested as
      immunodeficiencies. Often within these cells, cytokines and their receptors
      regulate the critical balance between life and death. It is becoming ever more
      apparent that within these effector cascades, Janus tyrosine kinases (Jak) and
      signal transducers and activators of transcription (Stat) act as key regulatory
      components. Invaluable knowledge about Jaks and Stats has arisen from mice made
      genetically deficient in these mqlecules, tumor models, and proteomics/genomics,
      which has begun to define their role in survival versus apoptosis. These findings
      have also suggested how Jaks and Stats might be manipulated for therapeutic
      intervention in lymphoid-derived diseases. This review seeks to focus on the role
      of Jak tyrosine kinases and Stat transcription factors in mediating the
      lymphocyte life cycle.

PMID- 15581393
TI  - Role of the IL-12/IL-23 system in the regulation of T-cell responses in central
      nervous system inflammatory demyelination.
AB  - Interleukin-12 (IL-12) has long been considered essential in T-cell-mediated
      autoimmune diseases, including multiple sclerosis (MS) and its animal model,
      experimental autoimmune encephalomyelitis (EAE). This is based on the strong
      capacity of IL-12 to induce T-cell activation and Th1 differentiation. However,
      recent data have shown that the perceived central role of IL-12 in CNS
      inflammatory demyelination is actually due to IL-23, a closely related cytokine
      sharing the p40 subunit and the beta1 receptor chain with IL-12. There appear to
      be three different aspects of IL-12 involvement in EAE: (1) disease-promoting
      effects of exogenous IL-12, particularly in relapsing-remitting EAE and adoptive
      transfer EAE; (2) lack of IL-12 requirement in EAE pathogenesis, as indicated by
      studies in knockout mice; and (3) immunoregulatory effects of IL-12. Together,
      these observations make IL-12 a less attractive target for therapeutic
      intervention in MS. IL-23 neutralization may be a better candidate for
      therapeutic intervention, and it remains to be established whether blocking IL-23
      with antibodies in adult mice will have the same effects as knocking out the IL
      23p19 gene. Current clinical trials of neutralizing anti-IL-12 antibodies in
      other immune-mediated diseases target the p40 subunit, thereby neutralizing both
      IL-12 and IL-23. Thus, new experimental data are expected to have important
      implications for therapy of human diseases.

PMID- 15581394
TI  - Measles virus infection and vaccination: potential role in chronic illness and
      associated adverse events.
AB  - Over the last decade, a number of concerns have arisen related to safety issues
      that have had an adverse effect on the public's trust, particularly among parents
      whose children are the primary recipient of the vaccine. Historically, the live
      attenuated measles virus (MV) vaccine and the combination multivalent measles,
      mumps, and rubella (MMR) vaccine have had a major impact on the health of
      children worldwide and have been extremely successful at preventing infectious
      diseases associated with three childhood viral pathogens. In this report, we
      describe MV infection, replication, pathogenesis, and immunization. MV is a viral
      pathogen that exhibits a number of complex processes that can effect its
      replication, pathogenesis, and the induction of an effective antiviral immune
      response. We describe the published literature as it relates to MV infection and
      immunization and report adverse events in an attempt to provide a balanced
      discussion and an historical perspective of the MMR vaccine and autism.

PMID- 15581395
TI  - A GABAergic cortical deficit dominates schizophrenia pathophysiology.
AB  - Several lines of evidence support the role of an epigenetic-induced GABAergic
      cortical dysfunction in schizophrenia psychopathology, which is probably
      dependent on an increase in the expression of DNA-methyltransferase-1 occurring
      selectively in GABAergic neurons. The key enzyme regulating GABA synthesis,
      termed glutamic acid decarboxylase 67 (GAD67) and the important
      neurodevelopmental protein called reelin are coexpressed in GABAergic neurons.
      Upon release, GABA and reelin bind to postsynaptic receptors located in
      dendrites, somata, or the axon initial segment of pyramidal neurons. Because
      GAD67 and reelin are downregulated in schizophrenia, it is suggested that
      schizophrenics may express GABAergic deficit-related alterations of pyramidal
      neuron function. A reduction of dendritic spines is a finding reported in the
      prefrontal cortex of schizophrenia patients. Because dendritic spines are
      innervated by glutamatergic axon terminals, very probably this reduction of
      dendritic spine expression is translated into a functional deficit of
      glutamatergic transmission. Plastic modifications of neuronal circuits are
      probably dependent on GABAergic transmitter tone, and it is likely that GABAergic
      dysfunction is at the root of synaptic plasticity deficits in schizophrenia.
      Thus, a possible avenue for the treatment of schizophrenia would be to address
      this GABAergic functional deficit using positive allosteric modulators of the
      action of GABA at GABAA receptors. Benzodiazepines (BZ) such as diazepam are
      effective in treating positive and negative symptoms of schizophrenia, but
      because they positively modulate GABAA receptors expressing alpha1 subunits,
      these BZs cause sedation and tolerance. In contrast, imidazenil, a full
      allosteric modulator of GABAA receptors expressing alpha5 subunits may reduce
      psychotic symptomatology without producing sedation. Hence, imidazenil should be
      appropriately studied as a prospective candidate for a pharmacological
      intervention in schizophrenia.

PMID- 15581396
TI  - A GABA, reelin, and the neurodevelopmental hypothesis of schizophrenia.
AB  - The GABA-reelin cortical connection (i.e., the expression and secretion of reelin
      by GABAergic cortical neurons) has been shown to function not only in the adult
      cortex but also during tangential migration of GABAergic neuroblasts. Therefore,
      it is of interest to focus on the possibility that a synergic action of these
      compounds (understood as a topobiological effect, implying place- and time
      dependent interactions) may have important implications in regulating
      developmental processes such as neuronal migration, dendritic sprouting,
      synaptogenesis, and axon pruning, as well as being involved in regulation of
      synaptic plasticity trough life. The present review summarizes the actual
      knowledge in this field and discusses the possible importance that a
      dysregulation of GABAergic and reelin systems may have as vulnerability factors
      for the etiology and pathophysiology of schizophrenia.

PMID- 15581397
TI  - Neuroanatomical and pharmacological evidence for a functional interaction between
      GABAergic and NPY-Y1 transmission in the amygdala of Y1R/LacZ transgenic mice.
AB  - Several lines of evidence indicate that GABA and neuropeptide Y (NPY) are
      functionally coupled and may interact in the regulation of fear- and anxiety
      induced behavior. Neuroanatomical studies demonstrated that GABA and NPY coexist
      in neurons of the amygdaloid complex and that NPY may directly modulate the
      activity of GABAergic neurons by stimulating Y1 receptors. By using a transgenic
      mouse model harboring a construct comprising the murine Y1 receptor gene promoter
      fused to a lacZ reporter gene (Y1R/LacZ mice), we showed that long-term treatment
      with positive (diazepam or abecarnil) or negative (FG7142) modulators of GABAA
      receptor function induced a marked increase or decrease, respectively, in Y1
      receptor gene expression in the amygdala. Furthermore, we demonstrated that a
      sustained increase in the brain concentrations of neuroactive steroids, induced
      by pharmacological treatment or by physiological conditions such as pregnancy,
      increases Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic
      mice, an effect similar to that induced by diazepam or abecarnil. These data
      provide evidence of a functional interaction between GABAergic and NPY-Y1
      mediated transmission and suggest that neuroactive steroids may play an important
      role in the regulation of the NPY transmission. Finally, our data support a role
      of Y1 receptors in the behavioral and neuroendocrine responses to stress that,
      however, appears to be independent on the activation of the GABAergic system.

PMID- 15581398
TI  - The BDNF gene: exemplifying complexity in Ca2+ -dependent gene expression.
AB  - Over the last 20 years, great effort has been made to decipher the molecular
      mechanisms used by cells to transform a cytosolic Ca2+ signal into specific,
      finely-controlled changes in gene expression. Several previous reviews addressed
      the variety of regulatory mechanisms that participate in Ca2+ -dependent gene
      expression in neurons (Carafoli et al., 2001; Mellstrom and Naranjo 2001; West et
      al., 2001). Nevertheless, recent discoveries have revealed new players and new
      interactions that tune this process. In this review, we will use the four
      promoters that regulate the expression of the brain-derived neurotrophic factor
      (BDNF) gene as a magnificent scenario in which these mechanisms intermingle to
      show the complexity of Ca2+ -dependent gene expression.

PMID- 15581399
TI  - Brain-derived neurotrophic factor activation of TrkB protects neurons from HIV
      1/gp120-induced cell death.
AB  - Patients with the human immunodeficiency virus type 1 (HIV-1) develop in the late
      phase of infection a complex of neurological signs termed Acquired Immune
      Deficiency Syndrome-Related Dementia (ADC). These patients exhibit cortical and
      subcortical atrophy. Considerable experimental data indicate that the HIV-1
      envelope glycoprotein gp120 may be one of the agents causing neuronal cell death.
      Gp120 causes neuronal cell death both in vitro and in vivo by activating a
      caspase-dependent apoptotic pathway, and in particular caspase-3. The
      neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to prevent
      gp120-mediated apoptosis of cerebellar granule cells by inhibiting caspase-3
      activation. However, the signal transduction pathway that contributes to the
      neuroprotective effects of BDNF has not been determined. BDNF binds with high
      affinity to the tyrosine kinase receptor TrkB and activates different
      intracellular signaling cascade including the extracellular signal-related
      kinases (ERK) and the phosphatidylinositol 3-kinase (PI3-K). Pharmacological
      inhibition of TrkB or ERK1/2, but not PI3-K, greatly reduced the ability of BDNF
      to block gp120-mediated apoptosis of cerebellar granule cells. These findings
      suggest that TrkB-mediated activation of ERK1/2 is the main signaling pathway
      that contributes to neuroprotection against gp120.

PMID- 15581400
TI  - Cerebellar granular cell cultures as an in vitro model for antidepressant drug
      induced neurogenesis.
AB  - Both preclinical and clinical evidence suggested that antidepressant drugs
      upregulate hippocampal cell proliferation and neurogenesis. In addition, direct
      evidence was recently published that hippocampal de novo cell proliferation is
      necessary for antidepressant action. Within this frame, we used primary cultures
      of rat cerebellar granule cells (CGC) as an in vitro model of central nervous
      system (CNS) to investigate whether a neurogenic response could be elicited also
      in the cerebellum, upon chronic treatment with selective serotonin reuptake
      inhibitors (SSRIs). Furthermore, we assayed the presence of neural precursor
      cells in CGC, possibly responsive to proliferation and differentiation stimuli.
      We found that 1 microM fluoxetine increased cell proliferation, as assayed by
      [3H]-thymidine incorporation. CGC immunocytochemical analysis with neural cell
      specific markers revealed the presence of granule neurons, glial cells, and a
      cell component that we named "round cells." Because only round cells displayed
      proliferation ability, as revealed by 5-bromo-2'-deoxyuridine (BrdU) labeling,
      they were further characterized. For this purpose, round cells were isolated and
      expanded by culturing in a serum-free medium, containing basic fibroblast growth
      factor (bFGF), before immunocytochemical analysis. We found that round cells were
      not immunoreactive for glial, neuronal, and oligodendrocyte markers, whereas they
      were immunoreactive for several immature neuronal markers. Accordingly, round
      cells could be induced to differentiate into astrocytes, neurons, and
      oligodendrocytes, either by withdrawing the mitogen bFGF or by exposing them to
      fluoxetine. These findings suggest that round cells in CGC possess the features
      and potentials of neural precursors, able to differentiate in mature neural cells
      upon a pharmacological simulum.

PMID- 15581401
TI  - Neurosteroidogenesis: relevance to neurosteroid actions in brain and modulation
      by psychotropic drugs.
AB  - Neurosteroids--i.e., steroid produced in brain ex novo or through metabolism of
      precursors--affect neuronal and brain functions through genomic and nongenomic
      mechanisms, depending on their molecular structure. Among neurosteroids, 3alpha
      hydroxylated, 5alpha-reduced metabolites of progesterone (3alpha-hydroxy,5alpha
      pregnan-20one/3alpha,5alpha-THP) and deoxycorticosterone (3alpha,21
      dihydroxy,5alpha-pregnan-20one/3alpha,5alpha-THDOC) are positive allosteric
      modulators of gamma-aminobutyric acid (GABA) action at GABAA receptors. In
      rodents, a reduction of their endogenous brain concentrations rapidly lowers the
      potency of GABA in eliciting GABAA receptor-mediated inhibitory postsynaptic
      currents. This effect is related to anxiety-like behavior, increased aggression,
      and a reduced sensitivity to the loss of righting reflex induced by GABAA
      receptor agonist or positive modulators. Conversely, enhancement of 3alpha,5alpha
      THP or 3alpha,5alpha-THDOC brain content results in anxiolysis,
      sedation/hypnosis, anticonvulsant, and anesthetic action. Different classes of
      psychotropic drugs--i.e., antidepressants, selected atypical antipsychotics,
      ethanol, gamma-hydroxybutyric acid--increase neurosteroid concentrations in
      brain, and these increases may be relevant to their pharmacological actions. Drug
      induced increases of neurosteroids in rodent brain are often associated with
      elevation of their plasma content, such that alterations of plasma steroid
      concentrations are assumed to reflect parallel changes in brain. Nevertheless,
      brain neurosteroid concentrations are uneven across various regions, and the dose
      dependence of their response to a pharmacological challenge shows brain-regional
      differences as well. These observations are consistent with the present knowledge
      on the distribution of steroidogenic enzymes in brain--they show not only a brain
      region, but also a cell-specific expression that may spatially and temporally
      determine the local concentrations of specific neurosteroids, either produced ex
      novo or through metabolism of steroid precursors that reach the brain through
      blood.

PMID- 15581402
TI  - Brain neurosteroids in gender-related aggression induced by social isolation.
AB  - Genetic, environmental, or hormonal factors and their interactions have been
      implicated in the expression of gender-related aggressive behavior in humans.
      Several independent lines of evidence support the role of hormonal and
      environmental factors in the aggressive behavior of experimental animals. Social
      isolation (SI) for 2-4 weeks in male but not in female mice results in the
      expression of aggression to a same-sex intruder. Long-term treatment (3 weeks)
      with anabolic steroids during SI in female mice induces aggressive behavior
      toward a male intruder of a severity similar to that observed in socially
      isolated (SI) male mice. The induced aggression in male and female mice is
      associated with a decrease of brain allopreg-nanolone (Allo). In SI male mice,
      aggression can be prevented by treatment with L-methionine (MET), which has also
      been shown to decrease reelin and GAD67 mRNA expression and maintain normal brain
      Allo content. The histone deacetylase inhibitor valproic acid can reverse this
      process, suggesting that histone tail acetylation may reverse the action of MET.
      We conclude that during social isolation, aggression can be controlled either by
      preventing Allo downregulation (e.g., by treatment with MET) or by direct
      administration of Allo or of agents (e.g., fluoxetine) that upregulate brain Allo
      content in SI mice.

PMID- 15581403
TI  - Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it
      be used to treat neurodegenerative diseases?
AB  - The mood stabilizing drug lithium has emerged as a robust neuroprotective agent
      in preventing apoptosis of neurons. Long-term treatment with lithium effectively
      protects primary cultures of rat brain neurons from glutamate-induced, NMDA
      receptor-mediated excitotoxicity. This neuroprotection is accompanied by an
      inhibition of NMDA-receptor-mediated calcium influx, upregulation of anti
      apoptotic Bcl-2, downregulation of pro-apoptotic p53 and Bax, and activation of
      cell survival factors. Lithium treatment antagonizes glutamate-induced activation
      of c-Jun-N-terminal kinase (JNK), p38 kinase, and AP-1 binding, which has a major
      role in cytotoxicity, and suppresses glutamate-induced loss of phosphorylated
      cAMP responsive element binding protein (CREB). Lithium also induces the
      expression of brain-derived neurotrophic factor (BDNF) and subsequent activation
      TrkB, the receptor for BDNF, in cortical neurons. The activation of BDNF/TrkB
      signaling is essential for the neuroprotective effects of this drug. In addition,
      lithium stimulates the proliferation of neuroblasts in primary cultures of CNS
      neurons. Lithium also shows neuroprotective effects in rodent models of diseases.
      In a rat model of stroke, post-insult treatment with lithium or valproate,
      another mood stabilizer, at therapeutic doses markedly reduces brain infarction
      and neurological deficits. This neuroprotection is associated with suppression of
      caspase-3 activation and induction of chaperone proteins such as heat shock
      protein 70. In a rat model of Huntington's disease (HD) in which an excitotoxin
      is unilaterally infused into the striatum, both long- and short-term pretreatment
      with lithium reduces DNA damage, caspase-3 activation, and loss of striatal
      neurons. This neuroprotection is associated with upregulation of Bcl-2. Lithium
      also induces cell proliferation near the injury site with a concomitant loss of
      proliferating cells in the subventricular zone. Some of these proliferating cells
      display neuronal or astroglial phenotypes. These results corroborate our findings
      obtained in primary neuronal cultures. The neuroprotective and neurotrophic
      actions of lithium have profound clinical implications. In addition to its
      present use in bipolar patients, lithium could be used to treat acute brain
      injuries such as stroke and chronic progressive neurodegenerative diseases.

PMID- 15581404
TI  - Protecting the brain: the search for a clinically effective neuroprotective drug
      for stroke.
AB  - The idea that it should be possible to develop a neuroprotective drug that
      protects the brain from some of the consequences of an acute ischaemic stroke has
      been in existence for some time and has developed from our increasing knowledge
      of the biochemical consequences of an acute ischaemic episode. A variety of drugs
      have been developed to interfere with these biochemical changes. However, while
      many of these compounds have been shown to be efficacious in animal models of
      stroke, none has succeeded in clinical trials and reached the market in the
      Western world. Partly as a result of these failures, guidelines have been
      published and further extended that detail criteria that should be met before a
      novel compound is progressed to clinical investigation. These guidelines are
      reviewed herein, and the author suggests the probability that none of the
      compounds that have previously failed clinically would have fulfilled the current
      selection criteria for advancement to clinical trial. It is proposed that NXY-059
      (Cerovive) is the first neuroprotective agent to reach the clinical trial phase
      that meets all the suggested guidelines for neuroprotective drug development, and
      the preclinical profile of this compound is reviewed.

PMID- 15581405
TI  - Adenosine A2A receptor antagonism and neuroprotection: mechanisms, lights, and
      shadows.
AB  - Adenosine A2A receptor antagonists are regarded as potential neuroprotective
      drugs, although the mechanisms underlying their effects remain to be elucidated.
      In this review, quinolinic acid (QA)-induced striatal toxicity was used as a tool
      to investigate the mechanisms of the neuroprotective effects of A2A receptor
      antagonists. After having examined the effects of selective A2A receptor
      antagonists toward different mechanisms of QA toxicity, we conclude that (1) the
      effect elicited by A2A receptor blockade on QA-induced glutamate outflow may be
      one of the mechanisms of the neuroprotective activity of A2A receptor
      antagonists; (2) A2A receptor antagonists have a potentially worsening influence
      on QA-dependent NMDA receptor activation; and (3) the ability of A2A receptor
      antagonists to prevent QA-induced lipid peroxidation does not correlate with the
      neuroprotective effects. These results suggest that A2A receptor antagonists may
      have either potentially beneficial or detrimental influence in models of
      neurodegeneration that are mainly due to increased glutamate levels or enhanced
      sensitivity of NMDA receptors, respectively.

PMID- 15581406
TI  - Transactivation of cell death signals by glutamate transmission in dopaminergic
      neurons.
AB  - The intrinsic susceptibility of dopaminergic neurons underlies the
      pathophysiology of Parkinson's disease and is possibly related to developmental
      injury in schizophrenia. However, the molecular substrates for this
      susceptibility are not well understood. We review the evidence of selective
      susceptibility of dopaminergic neurons to excessive glutamate receptor
      stimulation and discuss the molecular pathways that differentiate between
      physiological and pathological signaling leading to this particular form of
      neuronal death. In vitro as well as in vivo, activation of GluRAMPA causes
      concentration-dependent, severe pruning of neurites and selective death of
      dopaminergic neurons. In primary cultures of mesencephalon, this form of injury
      is mediated through release of calcium from intracellular stores (CICR), leading
      to loss of calcium homeostasis, oxidative stress, and activation of the
      transcription factor NFkappaB and the cell death protein p53. Post-translational
      modification of p53 may be an important target for neuroprotection in Parkinson's
      disease and perhaps in prevention of other neuropsychiatric disorders.

PMID- 15581407
TI  - Dopamine reuptake by norepinephrine neurons: exception or rule?
AB  - Dopamine reuptake by norepinephrine terminals can occur in brain areas such as
      the prefrontal cortex, the nucleus accumbens shell, and the bed nucleus of stria
      terminalis that are innervated, although unevenly, by both dopamine and
      norepinephrine neurons. Therefore the antidepressants that bind selectively the
      norepinephrine transporter might produce their therapeutic effect by raising the
      extracellular concentration of dopamine besides that of norepinephrine. Moreover,
      cocaine can be reinforcing even in knock-out mice for the dopamine transporter
      because it might raise synaptic dopamine in the nucleus accumbens shell by
      preventing its uptake by the norepinephrine transporter, an effect that could
      take place even in wild animals. Recently, it has also been suggested that
      dopamine can be co-released with norepinephrine by norepinephrine neurons,
      although it is not clear whether this feature might be related to a previous
      nonspecific uptake of dopamine by the norepinephrine transporter. In this review
      we discuss the potential role of the nonspecific uptake of dopamine by
      norepinephrine transporter in the mechanism of action of drugs of abuse,
      antipsychotics, and antidepressants.

PMID- 15581408
TI  - AMPA receptor blockade potentiates the stimulatory effect of L-DOPA on dopamine
      release in dopamine-deficient corticostriatal slice preparation.
AB  - The release of [3H]dopamine was measured in rat corticostriatal slice
      preparations that contained the striatum and the adjacent prefrontal cortex to
      maintained glutamatergic corticostriatal afferentation. These slices were
      prepared from either nontreated or 6-hydroxydopamine-pretreated rats. The slices
      were loaded with [3H]dopamine, submerged in a two-compartment bath so that the
      cortical region was contained in one compartment, the corpus callosum was passed
      through a silicone greased slot, and the striatal region was contained in the
      other compartment. The cortical and the striatal parts were superfused with Krebs
      bicarbonate buffer independently. The release of [3H]dopamine was determined from
      the striatal part at rest and in response to electrical stimulation of the
      cortical area. Electrical stimulation of the cortical part increased the release
      of [3H]dopamine from the striatal part of the slices, and this release was found
      to be higher after lesion of the nigrostriatal dopaminergic pathway with 6
      hydroxydopamine. Cortically evoked [3H]dopamine release was even higher in the
      presence of the dopamine precursor L-DOPA after 6-hydroxdopamine lesion.
      Perfusion of GYKI-53405, a noncompetitive AMPA receptor antagonist, in
      combination with L-DOPA further increased both basal and stimulation-evoked
      [3H]dopamine release, whereas GYKI-53405 by itself did not influence basal
      [3H]dopamine outflow from striatum. These findings indicate that, in parkinsonian
      striatum, the stimulatory effect of L-DOPA on dopamine release is potentiated by
      AMPA receptor blockade, and the antiparkinsonian effect of GYKI-53405 may be due
      to its L-DOPA sparing effect.

PMID- 15581409
TI  - Peripheral markers of glutamatergic dysfunction in neurological diseases: focus
      on ex vivo tools.
AB  - Since the proposal that excessive glutamatergic stimulation could be responsible
      for neuronal suffering and death, excitotoxicity and glutamate uptake deficits
      have been repeatedly confirmed to play a key role in the pathogenesis of
      different neurological diseases. Therefore, it is conceivable that assessing the
      glutamatergic system function directly in patients could be extremely useful for
      early diagnosis, prognostic evaluation, and optimization of the therapy. A
      possibility is offered by assessing glutamate levels in biological fluid, such as
      plasma and CSF, where increased levels of this amino acid have been reported in
      patients affected by stroke, amyotrophic lateral sclerosis (ALS), and AIDS
      dementia complex. However, the metabolic role of this amino acid acts as a
      confounding factor, and the possibility of directly assessing glutamatergic
      functional parameters, such as amino acid reuptake, would probably mirror closely
      the actual excitotoxic damage operative in each patient. Here we will describe
      our findings obtained in peripheral ex vivo cells, such as platelets and
      fibroblasts, both displaying a functional glutamate reuptake system. Consistent
      with a systemic-impairment assumption, glutamate uptake was shown to be reduced
      in peripheral cells of Alzheimer's disease, Down syndrome, Parkinson's disease,
      ALS, and stroke patients. Different systemic factors might be responsible for
      this phenomenon, including genetic predisposition, oxidative stress, and
      inflammatory response, raising new, exciting questions about the relevance of
      their possible interactions for the pathogenesis of neurological disorders.

PMID- 15581410
TI  - Cannabinoids and reward: interactions with the opioid system.
AB  - There is currently substantial evidence that Cannabis sativa derivates act on
      brain reward in a way very similar to other drugs of abuse and exert numerous
      pharmacological effects through their interaction with various neurotransmitters
      and neuromodulators. Among them, the endogenous opioids seem to play an important
      role in modulating the addictive properties of cannabinoids. Given the plethora
      of research activity on such a topic, this brief review is necessarily focused on
      cannabinoid/opioid interaction in reward-related events and restricted to the
      recent literature. Recent findings from our and other laboratories concerning
      cannabinoid reinforcing effects as revealed by behavioral animal models of
      addiction are here summarized. Evidence is then provided demonstrating a
      functional cross-talk between the cannabinoid and opioid systems in the mutual
      modulation of the addictive behavior; accordingly, very recent data from
      transgenic mice lacking either the cannabinoid CB1 or opioid receptors are also
      presented. Finally, the role of the endogenous cannabinoid system in relapse to
      opioids is investigated by means of extinction/reinstatement animal models
      following a period, even prolonged, of drug abstinence. Altogether, the reviewed
      studies provided a better understanding of the neurobiological mechanisms
      involved in cannabinoid actions and revealed a bidirectional interaction between
      the endogenous cannabinoid and opioid systems in reward that extends to central
      mechanisms underlying relapsing phenomena. Challenges for the future involve
      elucidation of the neuroanatomical substrates of cannabinoids action, even in
      light of the therapeutic potential of these compounds.

PMID- 15581411
TI  - Cannabinoid/opioid crosstalk in the central nervous system.
AB  - Promising therapeutic uses and a great variety of pharmacological effects are the
      leading forces that focus actual cannabinoid research. Cannabinoid and opioid
      systems share neuroanatomical, neurochemical, and paharmacological features. This
      fact supports the notion that actions induced by each one of these types of drugs
      involved an interaction between the endogenous opioid and endocannabinoid
      neuronal systems. Over the last decade our group and others have investigated
      cannabinoid/opioid crosstalk in the central nervous system by studying the
      mechanisms underlying pharmacological and biochemical interactions between the
      two systems in experimental paradigms of antinociception, drug reinforcement, and
      anxiety. The goal of this review is to revise the latest work done on this
      subject, with special emphasis on the research done with genetically modified
      animals. Whereas clinical progress is going ahead slowly, basic research in this
      area is progressing rapidly. Clinical applications derived from the
      cannabinoid/opioid crosstalk and based tightly on medical evidence are yet to
      come, but it is hoped that knowledge of this central messenger interaction will
      help to develop new alternatives for the treatment of some pathological states.

PMID- 15581412
TI  - Spatio-temporal regulation of neurotransmitter release by PKC; studies in adrenal
      chromaffin cells.
AB  - Activation of protein kinase C (PKC) seems to promote vesicle recruitment to the
      release-ready state prior to Ca2+ -triggered fusion in chromaffin cells. To
      understand spatio-temporal regulation of vesicle recruitment by PKC, we studied
      the effects of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), on
      the vesicle movements in living chromaffin cells by imaging with a fluorescence
      microscope-cooled CCD system. About 60 approximately 80% of the chromaffin
      vesicles showed a rapid movement, about 20% showed a moderate movement, and the
      rest showed slow/no movement in resting and post-stimulation. The vesicles with
      slow/no movement increased to 40% upon a depolarizing stimulation, and TPA
      increased this population to about 70%. TPA treatment, in addition, increased the
      number of visible chromaffin vesicles beneath the plasma membrane, suggesting
      that the potentiation of vesicle recruitment by PKC involves a substantial
      increase in the subplasmalemmal distribution of vesicles.

PMID- 15581413
TI  - 5-Lipoxygenase as a putative link between cardiovascular and psychiatric
      disorders.
AB  - There is evidence of an association between depression and anxiety and cardio-
      cerebro-vascular conditions, but the mechanisms of this association are unknown.
      Here we review a possible role for the 5-lipoxygenase (5-LOX) pathway. 5-LOX is
      an enzyme that, in association with 5-LOX-activating protein (FLAP), leads to the
      synthesis of leukotrienes from omega-6 arachidonic acid. Production of active
      leukotrienes can be reduced by dietary omega-3 fatty acids, which also are
      beneficial in cardiac and psychiatric (e.g., depression) pathologies. Human 5-LOX
      and FLAP gene polymorphisms are a risk factor in atherosclerosis and cardio
      cerebro-vascular pathologies; an overactive 5-LOX pathway is found in these
      diseases. Studies with 5-LOX-deficient transgenic mice suggest that 5-LOX
      activity may contribute to anxiety- and depression-like behaviors. Future
      research should characterize the role of the 5-LOX pathway in comorbid cardio
      cerebro-vascular and psychiatric disorders and in the therapeutic actions of
      dietary omega-3 fatty acids.

PMID- 15581414
TI  - Design of synthetic peptidic constructs for the vaccine development against viral
      infections.
AB  - The practical development of modern vaccines has been greatly advanced by the
      availability of synthetic antigens. The use of such synthetic antigens might be
      more acceptable for human therapy since synthetic peptides do not have any of the
      potential dangers associated with the induction of an infection by recombinant
      viruses. However, synthetic peptides alone are often not immunogenic enough, and
      a strong immunoadjuvant is usually employed for their elaboration. Unfortunately,
      only a few adjuvants used in experimental models are allowed for use in human
      beings. In this regard, different presentations of synthetic peptides such as
      incorporation into liposomes, modification of the lipophilic properties by means
      of a covalently coupled fatty acid moiety and the synthesis of larger constructs
      such as multiple antigenic peptides (MAP) have been demonstrated to yield
      efficient immunological reagents for the amplification in the analysis and
      induction of immune responses to a variety of infectious agents. This review
      outlines recent research on synthetic peptide immunology. The development of a
      MAP with a built-in adjuvant is highlighted as a robust method for vaccine
      design.

PMID- 15581415
TI  - Beta-Ala containing peptides: potentials in design and construction of bioactive
      peptides and protein secondary structure mimics.
AB  - In recent years, there has been increasing interest in de novo design and
      construction of novel synthetic peptides that mimic protein secondary structures,
      i.e., turns, helices and sheets. The unique structural influences exerted by
      unsubstituted, non-coded, non-chiral beta-amino acid, i.e., beta-alanine (beta
      Ala; 3- or beta- aminopropionic acid) on peptide backbone, when inserted into
      peptide chain comprised alpha-amino acids, offer an excellent opportunity to
      design and construct diverse well-defined three-dimensional structures. Our
      current understanding of folding-unfolding behavior of the beta-Ala residues
      relies primarily from an examination of conformational preferences of a large
      number of short cyclic- as well as acyclic beta-Ala containing peptides
      investigated using single crystal X-ray diffraction analysis. In addition,
      theoretical conformational energy calculations and different spectroscopic
      techniques: 1H NMR, FT-IR and CD, have also been employed although, to a lesser
      extent. The obtainable results tend to reveal overwhelming preferences of the
      beta-Ala moiety for the folded gauche (mu approximately +/-65+/-10 degrees
      conformation in cyclic- and for an extended trans (mu approximately +/-165+/-10
      degrees) as well as gauche (mu approximately +/-65+/-10 degrees) orientations in
      acyclic beta-Ala containing peptides. The results also indicate that in short
      linear beta-Ala containing peptides, the specific influence of selective
      neighboring side-chain substituents e.g. linear- or cyclic symmetrically
      C(alpha,alpha)-disubstituted glycines and other conformational constraints, may
      be significant in controlling the overall folded-unfolded topographical features
      across the two methylene units (-CbetaH2-CalphaH2-) of the beta-Ala residue.
      Taking into consideration the wide occurrence of beta-Ala moiety in animal and
      plant kingdoms and the remarkable structural versatility of the peptides
      incorporating beta-Ala residue(s), together with appreciable resistance towards
      enzymatic degradation, hold strong promise for biophysicists and biochemists not
      only to design molecules that fold to mimic protein secondary structures but also
      to develop potent peptide analogs and peptidomimetics displaying unique
      pharmaceutical properties.

PMID- 15581416
TI  - The physiology of learning and memory: role of peptides and stress.
AB  - The neuropeptides, as well as their respective receptors, are widely distributed
      throughout the mammalian central nervous system. During learning and memory
      processes, besides structural synaptic remodeling, changes are observed at
      molecular and metabolic levels with the alterations in neurotransmitter and
      neuropeptide synthesis and release. While there is consensus that brain
      cholinergic neurotransmission plays a critical role in the processes related to
      learning and memory, it is also well known that these functions are influenced by
      a tremendous number of neuropeptides and non-peptide molecules. Arginine
      vasopressin (AVP), oxytocin, angiotensin II, insulin, growth factors, serotonin
      (5-HT), melanin concentrating hormone, histamine, bombesin and gastrin-releasing
      peptide (GRP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), dopamine,
      corticotropin releasing factor (CRF) have modulatory effects on learning and
      memory. Among these peptides CCK, 5-HT and CRF play strategic roles in the
      modulation of memory processes under stressful conditions. CRF is accepted as the
      main neuropeptide involved in both physical and emotional stress, with a
      protective role during stress, possibly through the activation of the hypothalamo
      pitiuitary (HPA) axis. The peptide CCK has been proposed to facilitate memory
      processing and CCK-like immunoreactivity in the hypothalamus was observed upon
      stress exposure, suggesting that CCK may participate in the central control of
      stress response and stress-induced memory dysfunction. On the other hand, 5-HT
      appears to play a role in behaviors that involve a high cognitive demand and
      stress exposure activates serotonergic systems in a variety of brain regions. The
      physiological role and therapeutic efficacy of various neuropeptides and the
      impact of stress exposure in the acquisition and consolidation of memory will be
      reviewed thoroughly.

PMID- 15581417
TI  - Alpha-interferon and its effects on signalling pathways within cells.
AB  - Interferon-alpha (IFNalpha) is a recombinant protein widely used in the therapy
      of several neoplasms such as myeloma, renal cell carcinoma, epidermoid cervical
      and head and neck tumours and melanoma. IFNalpha, the first cytokine to be
      produced by recombinant DNA technology, has emerged as an important regulator of
      cancer cell growth and differentiation, affecting cellular communication and
      signal transduction pathways. However, the way by which tumour cell growth is
      directly suppressed by IFNalpha is not well known. Wide evidence exists on the
      possibility that cancer cells undergo apoptosis after the exposure to the
      cytokine. Here we will review the consolidate Signal transducer and activator of
      transcription (STAT)-dependent mechanism of action of IFNalpha and the supposed
      mechanism of apoptosis induction by IFNalpha. We will discuss data obtained by us
      and others on the triggering of the stress-dependent kinase pathway and on the
      modulation of protein synthesis machinery induced by IFNalpha and their
      correlations with the apoptotic process. Until today, inconsistent data have been
      obtained regarding the clinical effectiveness of IFNalpha in the therapy of solid
      tumours. In fact, the benefit of IFNalpha treatment is limited to some neoplasms
      while others are completely or partially resistant. The mechanisms of tumour
      resistance to IFNalpha have been studied in vitro. The alteration of JAK- Signal
      transducer and activator of transcription components of the IFNalpha-induced
      signalling, can be indeed a mechanism of resistance to IFN and cross talks
      between IFNalpha and survival signals has been also described. However, we have
      recently described a reactive mechanism of protection of tumour cells from the
      apoptosis induced by IFNalpha dependent on the epidermal growth factor (EGF)
      mediated Ras/extracellular signal regulated kinase (Erk) signalling. The
      involvement of the Ras->Erk pathway in the protection of tumour cells from the
      apoptosis induced by IFNalpha is further demonstrated by both Ras inactivation by
      RASN17 transfection and mitogen extracellular signal regulated kinase 1 (Mek-1)
      inhibition by exposure to PD098059. These data strongly suggest that the specific
      disruption of the latter could be a useful approach to potentiate the antitumour
      activity of IFNalpha against human tumours based on the new mechanistic insights
      achieved in the last years.

PMID- 15581418
TI  - Strategies for the construction and use of peptide and antibody libraries
      displayed on phages.
AB  - Combinatorial chemistry and biology have become popular methods for the
      identification of bio-active molecules in drug discovery. A widely used technique
      in combinatorial biology is "phage display", by which peptides, antibody
      fragments and enzymes are displayed on the surface of bacteriophages, and can be
      selected by simple procedures of biopanning. The construction of phage libraries
      of peptides or antibody fragments provides a huge source of ligands and bio
      active molecules that can be isolated from the library without laborious studies
      on antigen characteristics and prediction of ligand structure. This "irrational"
      approach for the construction of new drugs is extremely rapid and is now used by
      thousands of laboratories world-wide. The bottleneck in this procedure is the
      availability of large reliable libraries that can be used repeatedly over the
      years without loss of ligand expression and diversity. Construction of
      personalized libraries is therefore important for public and private laboratories
      engaged in the isolation of specific molecules for therapeutic or diagnostic use.
      Here we report the general strategies for constructing large phage peptide and
      antibody libraries, based on the experience of researchers who built the world's
      most widely used libraries. Particular attention is paid to advanced strategies
      for the construction, preservation and panning.

PMID- 15581419
TI  - Neuropeptides, neuropeptidases and brain asymmetry.
AB  - Brain asymmetry is understood as an anatomical, functional or neurochemical
      difference between the two hemispheres. It is not a static but rather a dynamic
      phenomenon in which both environmental and endogenous factors act as modulators.
      Aging modifies brain asymmetry, and an imbalance in specific asymmetries
      characterizes some brain disorders such as schizophrenia, depression, infantile
      autism or Alzheimer's disease. However, it is not clear whether these changes are
      a cause or a consequence of these disorders. Although this phenomenon has been
      extensively studied, its functional significance is not yet clear, and the
      neurochemical basis underlying anatomical or functional asymmetries in the brain
      is still poorly understood. In recent decades intensive research on the behaviour
      of neuropeptides has revealed asymmetries in their distribution in the brain, and
      there is evidence that the lateralized patterns of distribution are involved in
      the regulatory control of some neuropeptidase activities. Therefore, if these
      enzymatic activities are distributed asymmetrically, their endogenous substrates
      would presumably be affected in an asymmetrical way, as would the functions they
      are involved in. Here we review the most significant literature regarding human
      and animal brain asymmetry involving neuropeptides such as corticotropin
      releasing hormone, cholecystokinin, luteinizing hormone-releasing hormone,
      thyrotropin-releasing hormone and angiotensin II, as well as their
      neuropeptidases.

PMID- 15581420
TI  - The problem of amino acid complementarity and antisense peptides.
AB  - The review presents three hypotheses concerning the amino acid complementarity:
      1) the Mekler-Blalock antisense hypothesis; 2) the Root-Bernstein approach based
      on stereochemical complementarity of amino acids and anti-amino acids coded by
      anticodons read in parallel with the coding DNA strand; 3) Siemion hypothesis
      resulting from the periodicity of the genetic code. The current state of
      knowledge as well as the results of the implementations of these hypotheses are
      compared. A special attention is given to Root-Bernstein and Siemion hypotheses,
      which differ in only few points of the complementarity prediction. We describe
      methods of investigation of peptide-antipeptide pairing, including circular
      dichroism, mass spectrometry, affinity chromatography and other techniques. The
      biological applications of complementarity principle are considered, such as
      search for bioeffector-bioreceptor interaction systems, the influence of peptide
      antipeptide pairing on the activity of peptide hormones, and the application of
      antipeptides in immunochemistry. The possible role of amino acid-anti-amino acid
      interactions in the formation of the spatial structures of peptides, proteins and
      protein complexes is discussed. Such problems as the pairing preferences of
      protein-protein interfaces, the role of the pairing in the creation of disulfide
      bonds and the possible appearance of such interactions in beta-structure are also
      examined. The main intention of the paper is to bring the complementarity problem
      to the attention of the scientific community, as a possible tool in proteomics,
      molecular design and molecular recognition.

PMID- 15581421
TI  - The neuronal cytoskeleton as a potential therapeutical target in
      neurodegenerative diseases and schizophrenia.
AB  - The cytoskeleton plays a key role in maintaining the highly asymmetrical shape
      and structural polarity of neurons that are essential for neuronal physiology.
      Cytoskeletal reorganization plays a key role in neuritogenesis. In
      neurodegenerative diseases, the cytoskeleton is abnormally assembled and
      impairment of neurotransmission occurs. In Alzheimer's disease, abundant amyloid
      plaques and neurofibrillary tangles constitute the two major neuropathologic
      alterations present in the brain. Neurofibrillary tangles are formed of paired
      helical filaments consisting nearly entirely of the microtubule-associated
      protein tau. Under normal conditions tau binds to microtubules, stabilizing
      neuron structure and integrity. Hyperphosphorylation of tau is assumed to be the
      cause of formation of paired helical filaments. Another example of cytoskeletal
      abnormalities present in neurodegenerative diseases are the Lewy bodies
      considered as cytopathologic markers of Parkinson's disease. Lewy bodies are
      constituted of tubulin, MAP1, and MAP2. Neuronal shape, loss of dendrites and
      spines, as well as irregular distribution of neuronal elongations occur in
      specific brain areas of schizophrenic patients. Increase in non-phosphorylated
      MAP2 and MAP1B at hippocampus has been suggested as responsible for
      somatodendritic and cytoarchitectural abnormalities found in schizophrenia. In
      addition, neurofibrillary tangles are more frequent among schizophrenic patients
      who received pharmacologic antipsychotic treatment. Cumulative evidence suggests
      that neurodegenerative diseases and psychiatric illnesses are associated with
      cytoskeletal alterations in neurons that, in turn, loose synaptic connectivity
      and the ability to transmit incoming axonal information to the somatodendritic
      domain. We will review evidence supporting that the neuronal cytoskeleton is
      disrupted in neurodegenerative and some psychiatric diseases, and therefore could
      be a target for drug therapy. In addition, current data indicating that
      melatonin, a hormone secreted by the pineal gland, promotes neuritogenesis
      through cytoskeletal rearrangements and in addition to the potential therapeutic
      use of melatonin in neurodegenerative diseases will be discussed.

PMID- 15581422
TI  - Molecular, functional and structural properties of the prolyl oligopeptidase of
      Trypanosoma cruzi (POP Tc80), which is required for parasite entry into mammalian
      cells.
AB  - We have demonstrated that the 80 kDa POP Tc80 (prolyl oligopeptidase of
      Trypanosoma cruzi) is involved in the process of cell invasion, since specific
      inhibitors block parasite entry into non-phagocytic mammalian host cells. In
      contrast with other POPs, POP Tc80 is capable of hydrolysing large substrates,
      such as fibronectin and native collagen. In this study, we present the cloning of
      the POPTc80 gene, whose deduced amino acid sequence shares considerable identity
      with other members of the POP family, mainly within its C-terminal portion that
      forms the catalytic domain. Southern-blot analysis indicated that POPTc80 is
      present as a single copy in the genome of the parasite. These results are
      consistent with mapping of POPTc80 to a single chromosome. The active recombinant
      protein (rPOP Tc80) displayed kinetic properties comparable with those of the
      native enzyme. Novel inhibitors were assayed with rPOP Tc80, and the most
      efficient ones presented values of inhibition coefficient Ki < or = 1.52 nM.
      Infective parasites treated with these specific POP Tc80 inhibitors attached to
      the surface of mammalian host cells, but were incapable of infecting them.
      Structural modelling of POP Tc80, based on the crystallized porcine POP,
      suggested that POP Tc80 is composed of an alpha/beta-hydrolase domain containing
      the catalytic triad Ser548-Asp631-His667 and a seven-bladed beta-propeller non
      catalytic domain. Docking analysis suggests that triple-helical collagen access
      to the catalytic site of POP Tc80 occurs in the vicinity of the interface between
      the two domains.

PMID- 15581423
TI  - Chaperone-like properties of the prodomain of TNFalpha-converting enzyme (TACE)
      and the functional role of its cysteine switch.
AB  - The prodomain of TACE [TNFalpha (tumour necrosis factor alpha)-converting enzyme]
      is essential for the secretion of the functional enzyme. Previously, we showed
      that a TACE truncate was not secreted in the absence of the prodomain and that it
      was subjected to intracellular degradation. In the present study, we show that
      full-length TACE was also degraded when expressed without the prodomain. We
      demonstrate that the prodomain can rescue TACE's secretion in trans, suggesting
      an intramolecular chaperone function. We addressed the question whether a
      cysteine switch consensus motif is needed for the secretion of active TACE. The
      cysteine switch mutants [C184A (Cys184-->Ala)] of TACE resembled the wild-type
      functionally and in their sensitivity to inhibitors. Interestingly, TACE zymogen
      forms expressed in the context of the C184A mutation were susceptible to
      intracellular degradation, suggesting that the prodomain-bound TACE zymogen may
      be more accessible to intracellular proteinases when compared with mature TACE.
      Two independent findings confirmed that the catalytic domain of TACE is in a more
      open state when bound to its prodomain: (i) core tryptophan residues were exposed
      to the solvent in the procatalytic domain complex and (ii) LysC rapidly
      proteolysed the procatalytic domain complex but not mature TACE. Therefore the
      prodomain of TACE is a specific intramolecular chaperone that aids in the
      secretion of this enzyme, while keeping the catalytic domain in a relatively open
      conformation. The cysteine switch of TACE is not essential for the secretion of
      the functional enzyme, but may prevent intracellular degradation of the TACE
      zymogen.

PMID- 15581424
TI  - Personal health promotion at US medical schools: a quantitative study and
      qualitative description of deans' and students' perceptions.
AB  - BACKGROUND: Prior literature has shown that physicians with healthy personal
      habits are more likely to encourage patients to adopt similar habits. However,
      despite the possibility that promoting medical student health might therefore
      efficiently improve patient outcomes, no one has studied whether such promotion
      happens in medical school. We therefore wished to describe both typical and
      outstanding personal health promotion environments experienced by students in
      U.S. medical schools. METHODS: We collected information through four different
      modalities: a literature review, written surveys of medical school deans and
      students, student and dean focus groups, and site visits at and interviews with
      medical schools with reportedly outstanding student health promotion programs.
      RESULTS: We found strong correlations between deans' and students' perceptions of
      their schools' health promotion environments, including consistent support of the
      idea of schools' encouraging healthy student behaviors, with less consistent
      follow-through by schools on this concept. Though students seemed to have thought
      little about the relationships between their own personal and clinical health
      promotion practices, deans felt strongly that faculty members should model
      healthy behaviors. CONCLUSIONS: Deans' support of the relationship between
      physicians' personal and clinical health practices, and concern about their
      institutions' acting on this relationship augurs well for the role of student
      health promotion in the future of medical education. Deans seem to understand
      their students' health environment, and believe it could and should be improved;
      if this is acted on, it could create important positive changes in medical
      education and in disease prevention.

PMID- 15581425
TI  - Randomised, controlled trial of N-acetylcysteine for treatment of acute
      exacerbations of chronic obstructive pulmonary disease [ISRCTN21676344].
AB  - BACKGROUND: Prophylactic treatment with N-acetylcysteine (NAC) for 3 months or
      more is associated with a reduction in the frequency of exacerbations of chronic
      obstructive pulmonary disease (COPD). This raises the question of whether
      treatment with NAC during an acute exacerbation will hasten recovery from the
      exacerbation. METHODS: We have examined this in a randomised, double-blind,
      placebo controlled trial. Subjects, admitted to hospital with an acute
      exacerbation of COPD, were randomised within 24 h of admission to treatment with
      NAC 600 mg b.d. (n = 25) or matching placebo (n = 25). Treatment continued for 7
      days or until discharge (whichever occurred first). To be eligible subjects had
      to be > or = 50 years, have an FEV1 < or = 60% predicted, FEV1/VC < or = 70% and
      > or = 10 pack year smoking history. Subjects with asthma, heart failure,
      pneumonia and other respiratory diseases were excluded. All subjects received
      concurrent treatment with prednisone 40 mg/day, nebulised salbutamol 5 mg q.i.d
      and where appropriate antibiotics. FEV1, VC, SaO2 and breathlessness were
      measured 2 hours after a dose of nebulised salbutamol, at the same time each day.
      Breathlessness was measured on a seven point Likert scale. RESULTS: At baseline
      FEV1 (% predicted) was 22% in the NAC group and 24% in the control group. There
      was no difference between the groups in the rate of change of FEV1, VC, SaO2 or
      breathlessness. Nor did the groups differ in the median length of stay in
      hospital (6 days for both groups). CONCLUSIONS: Addition of NAC to treatment with
      corticosteroids and bronchodilators does not modify the outcome in acute
      exacerbations of COPD.

PMID- 15581427
TI  - Successful obstetrical management of 110-day intertwin delivery interval without
      cerclage: counseling and conservative management approach to extreme asynchronous
      twin birth.
AB  - BACKGROUND: This report describes a patient counseling approach and non-surgical
      management of a dichorionic-diamniotic twin pregnancy where delivery of the
      second twin followed the delivery of the first by 110 days. CASE PRESENTATION: An
      early transvaginal sonogram at 19 1/2 weeks suggested cervical dilation with
      protruding amniotic membranes. Tocolytic and antibiotic therapy was initiated; no
      cerclage was placed. Spontaneous rupture of membranes and cord prolapse occurred
      48 h later, resulting in delivery of a stillborn female infant. Conservative
      management was offered after counseling for possible risks associated with
      maternal sepsis, need for extended hospitalization, potential for hysterectomy
      and death. The cervix appeared closed after delivery and the umbilical cord was
      ligated, with subsequent spontaneous cord retraction in utero. Reassuring fetal
      status was observed for twin B without evidence of contractions or
      chorioamnionitis. A viable male infant (2894 g) was delivered vaginally at 35 1/2
      weeks. CONCLUSIONS: This report outlines a counseling approach useful for
      patients with premature delivery of one twin, and presents application of
      conservative obstetrical management principles for the aftercoming twin even when
      delivery interval is extreme.

PMID- 15581426
TI  - Leptin and insulin stimulation of signalling pathways in arcuate nucleus
      neurones: PI3K dependent actin reorganization and KATP channel activation.
AB  - BACKGROUND: Leptin and insulin are long-term regulators of body weight. They act
      in hypothalamic centres to modulate the function of specific neuronal subtypes,
      by altering transcriptional control of releasable peptides and by modifying
      neuronal electrical activity. A key cellular signalling intermediate, implicated
      in control of food intake by these hormones, is the enzyme phosphoinositide 3
      kinase. In this study we have explored further the linkage between this enzyme
      and other cellular mediators of leptin and insulin action on rat arcuate nucleus
      neurones and the mouse hypothalamic cell line, GT1-7. RESULTS: Leptin and insulin
      increased the levels of various phosphorylated signalling intermediates,
      associated with the JAK2-STAT3, MAPK and PI3K cascades in the arcuate nucleus.
      Inhibitors of PI3K were shown to reduce the hormone driven phosphorylation
      through the PI3K and MAPK pathways. Using isolated arcuate neurones, leptin and
      insulin were demonstrated to increase the activity of KATP channels in a PI3K
      dependent manner, and to increase levels of PtdIns(3,4,5)P3. KATP activation by
      these hormones in arcuate neurones was also sensitive to the presence of the
      actin filament stabilising toxin, jasplakinolide. Using confocal imaging of
      fluorescently labelled actin and direct analysis of G- and F-actin concentration
      in GT1-7 cells, leptin was demonstrated directly to induce a re-organization of
      cellular actin, by increasing levels of globular actin at the expense of
      filamentous actin in a PI3-kinase dependent manner. Leptin stimulated PI3-kinase
      activity in GT1-7 cells and an increase in PtdIns(3,4,5)P3 could be detected,
      which was prevented by PI3K inhibitors. CONCLUSIONS: Leptin and insulin mediated
      phosphorylation of cellular signalling intermediates and of KATP channel
      activation in arcuate neurones is sensitive to PI3K inhibition, thus
      strengthening further the likely importance of this enzyme in leptin and insulin
      mediated energy homeostasis control. The sensitivity of leptin and insulin
      stimulation of KATP channel opening in arcuate neurones to jasplakinolide
      indicates that cytoskeletal remodelling may be an important contributor to the
      cellular signalling mechanisms of these hormones in hypothalamic neurones. This
      hypothesis is reinforced by the finding that leptin induces actin filament
      depolymerization, in a PI3K dependent manner in a mouse hypothalamic cell line.

PMID- 15581428
TI  - Transthoracic coronary flow reserve and dobutamine derived myocardial function: a
      6-month evaluation after successful coronary angioplasty.
AB  - After percutaneous transluminal coronary angioplasty (PTCA), stress
      echocardiography and gated single photon emission computerized tomography (g
      SPECT) are usually performed but both tools have technical limitations. The
      present study evaluated results of PTCA of left anterior descending artery (LAD)
      six months after PTCA, by combining transthoracic Doppler coronary flow reserve
      (CFR) and color Tissue Doppler (C-TD) dobutamine stress. Six months after PTCA of
      LAD, 24 men, free of angiographic evidence of restenosis, underwent standard
      Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal
      diastolic coronary flow ratio) and C-TD at rest and during dobutamine stress to
      quantify myocardial systolic (Sm) and diastolic (Em and Am, Em/Am ratio) peak
      velocities in middle posterior septum. Patients with myocardial infarction,
      coronary stenosis of non-LAD territory and heart failure were excluded. According
      to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion
      defects. The 2 groups were comparable for age, wall motion score index (WMSI) and
      C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 +/-
      0.4 versus 2.87 +/- 0.6, p < 0.002) and septal Sm at high-dose dobutamine (p <
      0.01), with higher WMSI (p < 0.05) and stress-echo positivity of LAD territory in
      5/11 patients. In the overall population, CFR was related negatively to high
      dobutamine WMSI (r = -0.50, p < 0.01) and positively to high-dobutamine Sm of
      middle septum (r = 0.55, p < 0.005). In conclusion, even in absence of epicardial
      coronary restenosis, stress perfusion imaging reflects a physiologic impairment
      in coronary microcirculation function whose magnitude is associated with the
      degree of regional functional impairment detectable by C-TD.

PMID- 15581429
TI  - Population genetic structure of Anopheles gambiae mosquitoes on Lake Victoria
      islands, west Kenya.
AB  - BACKGROUND: Understanding the genetic structure of island Anopheles gambiae
      populations is important for the current tactics in mosquito control and for the
      proposed strategy using genetically-modified mosquitoes (GMM). Genetically
      isolated mosquito populations on islands are a potential site for testing GMM.
      The objective of this study was to determine the genetic structure of A. gambiae
      populations on the islands in Lake Victoria, western Kenya. METHODS: The genetic
      diversity and the population genetic structures of 13 A. gambiae populations from
      five islands on Lake Victoria and six villages from the surrounding mainland area
      in the Suba District were examined using six microsatellite markers. The distance
      range of sampling sites varied between 2.5 and 35.1 km. RESULTS: A similar level
      of genetic diversity between island mosquito populations and adjacent mainland
      populations was found. The average number of alleles per locus was 7.3 for the
      island populations and 6.8 for the mainland populations. The average observed
      heterozygosity was 0.32 and 0.28 for the island and mainland populations,
      respectively. A low but statistically significant genetic structure was detected
      among the island populations (FST = 0.019) and between the island and mainland
      populations (FST = 0.003). A total of 12 private alleles were found, and nine of
      them were from the island populations. CONCLUSION: A level of genetic
      differentiation between the island and mainland populations was found. Large
      extent of gene flow between the island and mainland mosquito populations may
      result from wind- or human-assisted dispersal. Should the islands on Lake
      Victoria be used as a trial site for the release program of GMM, mosquito
      dispersal between the islands and between the island and the mainland should be
      vigorously monitored.

PMID- 15581430
TI  - Interaction among general practitioners age and patient load in the prediction of
      job strain, decision latitude and perception of job demands. A cross-sectional
      study.
AB  - BACKGROUND: It is widely recognized and accepted that job strain adversely
      impacts the workforce. Individual responses to stressful situations can vary
      greatly and it has been shown that certain people are more likely to experience
      high levels of stress in their job than others. Studies highlighted that there
      can be age differences in job strain perception. METHODS: Cross-sectional postal
      survey of 300 Lithuanian general practitioners. Psychosocial stress was
      investigated with a questionnaire based on the Reeder scale. Job demands were
      investigated with the Karasek scale. The analysis included descriptive
      statistics; logistic regression beta coefficients to find out predictors and
      interactions between characteristics and predictors. RESULTS: Response rate was
      66% (N = 197). Logistic regression as significant predictors for job strain
      assigned - duration of work in primary care; for job demands- age and duration of
      working in primary care; for decision latitude- age and patient load.The
      interactions with regard to job strain showed that GP's age and job strain are
      negatively associated to a low patient load. Lower decision latitude for older GP
      age is strongly related to higher patient load. Job demands and GP age are
      slightly positively related at low patient load. CONCLUSIONS: Lithuanian GP's
      have high patient load and are at risk of stress, they have high job demands and
      low decision latitude. Older GP's perceive less strain, lower job demands and
      higher decision latitude in case of low patient load. Young GP's decision
      latitude has week association to patient load. Regarding to the changes in
      patient load younger GP's perceive it more sensitively as changes in job demands.

PMID- 15581431
TI  - DEDB: a database of Drosophila melanogaster exons in splicing graph form.
AB  - BACKGROUND: A wealth of quality genomic and mRNA/EST sequences in recent years
      has provided the data required for large-scale genome-wide analysis of
      alternative splicing. We have capitalized on this by constructing a database that
      contains alternative splicing information organized as splicing graphs, where all
      transcripts arising from a single gene are collected, organized and classified.
      The splicing graph then serves as the basis for the classification of the various
      types of alternative splicing events. DESCRIPTION: DEDB
      http://proline.bic.nus.edu.sg/dedb/index.html is a database of Drosophila
      melanogaster exons obtained from FlyBase arranged in a splicing graph form that
      permits the creation of simple rules allowing for the classification of
      alternative splicing events. Pfam domains were also mapped onto the protein
      sequences allowing users to access the impact of alternative splicing events on
      domain organization. CONCLUSIONS: DEDB's catalogue of splicing graphs facilitates
      genome-wide classification of alternative splicing events for genome analysis.
      The splicing graph viewer brings together genome, transcript, protein and domain
      information to facilitate biologists in understanding the implications of
      alternative splicing.

PMID- 15581438
TI  - Pulmonary arterial hypertension: new treatments are improving outcomes.

PMID- 15581439
TI  - Acting on synergies between clinic and community strategies to improve preventive
      medicine.

PMID- 15581440
TI  - Does continuity of care improve patient outcomes?
AB  - OBJECTIVE: Continuity of care is a cornerstone of primary care that has been
      promoted by recent trends in medical education and in the way health care
      delivery is organized. We sought to determine the effect of sustained continuity
      of care (SCOC) on the quality of patient care. DATA SOURCES: We conducted a
      systematic review of all articles in Medline (January 1966 to January 2002),
      Educational Resources Information Center (ERIC), and PSYCH INFO using the terms
      "continuity of care" or "continuity of patient care." We identified additional
      titles of candidate articles by reviewing the bibliographies of articles from our
      original MEDLINE search, contacting experts in primary care, health care
      management, and health services research, and by reviewing bibliographies of
      textbooks of primary care and public health. STUDY SELECTION AND DATA EXTRACTION:
      Two investigators (MDC, SHJ) independently reviewed the full text to exclude
      articles that did not fulfill search criteria. Articles excluded were those that
      focused on physicians-in-training, on SCOC in a non-primary care setting, such as
      an inpatient ward, or on transitions from inpatient to the outpatient setting. We
      also excluded articles that did not correlate SCOC to a quality of care measure.
      DATA SYNTHESIS: From 5070 candidate titles, we examined the full text of 260
      articles and found 18 (12 cross-sectional studies, 5 cohort studies and 1
      randomized controlled trial) that fulfilled our criteria. Five studies focused on
      patients with chronic illness (eg, asthma, diabetes). RESULTS: No studies
      documented negative effects of increased SCOC on quality of care. SCOC is
      associated with patient satisfaction (4 studies), decreased hospitalizations and
      emergency department visits (7 studies), and improved receipt of preventive
      services (5 studies). CONCLUSIONS: SCOC improves quality of care, and this
      association is consistently documented for patients with chronic conditions.
      Programs to promote SCOC may best maximize impact by focusing on populations with
      chronic conditions.

PMID- 15581442
TI  - Prescribing herbal medications appropriately.

PMID- 15581441
TI  - Rupturing bullae not responding to antibiotics.

PMID- 15581443
TI  - Clinical inquiries. Are antibiotics effective in preventing pneumonia for nursing
      home patients?

PMID- 15581444
TI  - Clinical inquiries. What is the best way to evaluate and manage diarrhea in the
      febrile infant?

PMID- 15581445
TI  - Clinical inquiries. Is antibiotic prophylaxis effective for recurrent acute
      otitis media?

PMID- 15581446
TI  - Clinical inquiries. What is the diagnostic approach to a 1-year-old with chronic
      cough?

PMID- 15581447
TI  - Clinical inquiries. Can transvaginal ultrasound detect endometrial disease among
      asymptomatic postmenopausal patients?

PMID- 15581448
TI  - Clinical inquiries. How useful is ultrasound to evaluate patients with
      postmenopausal bleeding?

PMID- 15581449
TI  - Forest plots: data summaries at a glance.

PMID- 15581450
TI  - [Inserm-FRSQ: it's forty already!].

PMID- 15581451
TI  - [Susceptibility].

PMID- 15581452
TI  - [Hepatic stem cells: it's quite an undertaking!].

PMID- 15581453
TI  - [Understanding glutamatergic neurons in mammalians: "menage a trois"].

PMID- 15581454
TI  - [Leber congenital amaurosis: retinol dehydrogenases are the culprit].

PMID- 15581455
TI  - [PCSK9: a new gene involved in familial hypercholesteremia].

PMID- 15581456
TI  - [Molecular bases of acrodermatitis enteropathica].

PMID- 15581457
TI  - [Neuropathies and small heat shock proteins].

PMID- 15581458
TI  - [When Staphylococcus needs iron, it prefers heme's].

PMID- 15581459
TI  - [Extinction of large carnivorous canides: when the strongest's reason is not
      always the best!].

PMID- 15581460
TI  - [Redeployment of the Six genes in evolution].
AB  - It has become clear that during evolution, efficient molecular mechanisms are
      used over and over again to achieve various patterning tasks. The Six gene story
      illustrates a new aspect of the molecular conservation during embryogenesis.
      Members of the Six gene family have been identified on the basis of sequence
      homology with Drosophila sine oculis gene, which acts within a network of genes
      including eyeless (Pax family), eyes absent (Eya family) and dachshund (Dach
      family) to trigger compound eye organogenesis. Some aspects of the regulatory
      complex operating in Drosophila appear to be conserved during vertebrate eye
      patterning, but also for other differentiation processes. In this regard, Six1 is
      required nonetheless during myogenesis, but also for kidney, thymus, inner ear,
      nose, lacrimal and salivary gland organogenesis. These phenotypes are reminiscent
      of those previously described for Eya and Pax mutants, suggesting a functional
      link between these factors during mammalian organogenesis.

PMID- 15581461
TI  - [Ontogenesis of primordial germ cells].
AB  - In sexually reproducing animals all gametes of either sex arise from primordial
      germ cells (PGC). PGC represent a small cell population, appearing early during
      embryo development. They represent a key cell population responsible for the
      survival and the evolution of a species. Indeed, the production of gametes will
      assure fertilisation and therefore the establishment of the next generation.
      Until recently only few laboratories were working on PGC biology. A new interest
      emerged since these cells have the ability to function as pluripotent stem cells
      when established as cell lines. Indeed, like embryonic stem cells (ESC),
      embryonic germ cells (EGC) are able to differentiate in a wide variety of
      tissues. In vivo, EGC are able, after injection into a host blastocyst cavity to
      colonise the inner cell mass and to participate in embryonic development. In
      vitro studies in human and mouse have also shown their capacity to differentiate
      into a large variety of cell types allowing the study of processes involved in
      cardiomyocyte, haematopoietic, neuronal and myogenic differentiation pathways. We
      present here the last updates of PGC ontogeny focusing mainly on the murine
      model.

PMID- 15581462
TI  - [Biliary function and its regulation].
AB  - Biliary function is essential for intestinal absorption of fat, homeostasis of
      cholesterol and elimination of diverse metabolic end-products. Bile is elaborated
      in hepatocyte canaliculi and modified by cholangiocytes through both secretion
      and absorption processes. The main determinant of bile formation is an osmotic
      filtration process resulting from active transport of bile acids and other
      osmotic solutes. Most of the membrane transporters ensuring bile formation have
      now been identified. The expression of these membrane transporters is regulated
      in particular through transcriptional mechanisms under the control of nuclear
      receptors activated by ligands, such as bile acids, which act as endogenous
      steroids synthesized from cholesterol in hepatocytes. Monogenic cholestatic
      diseases illustrate the key role of membrane transporters in biliary function.
      Bile acids are potent modulators of transporters and thus trigger an adaptative
      response to cholestasis. The extent of this adaptative response could explain the
      compelling phenotypic variability of cholestatic diseases in childhood and
      adults. The firstline medical treatment is currently ursodeoxycholic acid. In
      case of failure of this medical treatment, liver transplantation is required.
      Recent progress in the molecular pathogenesis of bile formation and cholestatic
      liver diseases is expected to provide the design for drugs targeted to the
      molecular abnormalities responsible of cholestatic diseases.

PMID- 15581463
TI  - [Vascular risk factors and renal failure].
AB  - Patients with chronic kidney disease (CKD) have a substantially increased risk of
      cardiovascular disease (CVD) compared with the general population. The high
      prevalence of established traditional risk factors for atherosclerosis (diabetes,
      hypertension, dyslipidemia) in these patients undoubtedly contributes to the
      accelerated rate of vascular disease. In addition, several hypotheses have
      emerged to explain the high prevalence of CVD in patients with chronic renal
      failure. Growing evidence has been gathered over the last 15 years regarding the
      role of uremia-related risk factors such as inflammation and oxidant stress in
      the pathogenesis of atherosclerosis in subjects with renal failure. This paper
      will review current knowledge regarding the potential role of these non
      traditional or uremia-related risk factors for atherosclerosis with special
      emphasis on prevalence, cardiac risk, and management in patients with CKD.

PMID- 15581464
TI  - [Thrombolysis and acute cerebral infarction].
AB  - Thrombolytic therapy are the most important advance in the management of acute
      ischemic stroke and has been evaluated in several randomised trials. Thrombolysis
      with recombinant tissue plasminogen activator (rt-Pa) is effective within 3 h of
      onset of ischemic stroke and this efficacy is similar between different stroke
      subtypes. New trials will determine if extension of this time-window can be
      substantiated. Therapy beyond the 3-hour window, with intra-arterial
      thrombolysis, appears to improve outcome but are applicable to selected group of
      patients. Thrombolytic drugs can also carry an important risk (5 % to 10 %) of
      brain hemorrhage and edema that can prove fatal. The risk of symptomatic
      intracranial hemorrhage is directly proportional to stroke severity and inversely
      proportional to time to treatment. There is a growing interest in the use of MRI
      in acute ischemic stroke. It helps identify location of early cerebral ischemia
      and provides valuable information not only of the penumbra but also of vessel
      occlusion. Its use might help in selecting patients who will benefit most from
      treatment such as thrombolysis. In spite of these results, community use of
      thrombolytic therapy remains dismally low. Many physicians and medical centers
      are not presently equipped or willing to give thrombolytic drugs for stroke
      treatment. Increasing stroke awareness in the community, creating stroke unit and
      physicians education are necessary to extend the effective use of acute treatment
      in cerebral infarct to a larger group of patients.

PMID- 15581465
TI  - [Cerebral tolerance: a promising choice towards new treatments for neurologic
      diseases].
AB  - Ischemia and seizures are common diseases that result in neuronal death. To-date,
      there are no available treatments to block or reverse neuronal death pathways in
      patients who suffer from these diseases. All drugs that have been shown to be
      neuroprotective in animal models have failed in human trials. Therefore, the
      potential of preventative strategies for therapy is increasingly explored.
      Experimental studies have demonstrated that a brief cerebral ischemic insult,
      that is not harmful by itself, results in a temporary protective adaptation in
      the brain against a subsequent ischemic episode that would otherwise be lethal.
      This process, termed ischemic preconditioning, has been confirmed in different
      models of cerebral ischemia. A similar phenomenon observed after a mild epileptic
      insult conferred a transitory tolerance to a subsequent epileptic episode. This
      process is termed epileptic tolerance. Other stresses, like hyperthermia or
      spreading depression, also enhanced brain resistance to detrimental effects of
      ischemic or epileptic injury. Recently, a cross tolerance between ischemia and
      epilepsy has been reported. Also, some retrospective studies in humans suggest
      that endogenous ischemic preconditioning exists in the brain. Altogether these
      insights of brain tolerance point to the future discovery of potentially useful
      targets for acute neuroprotection as well as preventive therapy.

PMID- 15581466
TI  - [Myocardial dysfunction and septic shock].
AB  - Myocardial dysfunction frequently accompanies severe sepsis and septic shock. It
      is now clear that such a myocardial depression, as evidenced by biventricular
      alteration, is present during the early phase of sepsis in most patients.
      Myocardial depression exists despite a fluid loading-dependent hyperdynamic state
      and usually recovers within 7 to 10 days in survivors. Myocardial dysfunction
      does not appear to be due to irreversible structural abnormalities nor to
      myocardial hypoperfusion, but rather linked to many circulating mediators
      including cytokines. At a cellular level, reduced myocardial contractility could
      be related in part to apoptosis and induced by both nitric oxide-dependent and
      nitric oxide-independent mechanisms. However, whatever the mechanism involved, it
      leads to calcium homeostasis abnormality. The present review describes both the
      diagnosis procedure and the molecular and cellular pathways of sepsis-induced
      myocardial depression.

PMID- 15581467
TI  - [Protagonists of innate immunity during in Salmonella infections].
AB  - Salmonella are facultative intracellular Gram-negative bacteria that are found
      ubiquitously in nature and have the ability to infect a wide range of hosts
      including humans, domesticated, wild mammals, and birds. The principal clinical
      manifestations associated with Salmonella infection in humans are enteric fever
      (typhoid and paratyphoid) and a self-limiting gastroenteritis (salmonellosis).
      Additionally, silent carriage of this bacterium is frequent and contributes to
      disease dissemination. Typhoid fever still represents a major public health
      problem in many developing countries. On the other hand, industrialized countries
      experience an increased incidence of nontyphoidal Salmonella infections with most
      cases tracing back to food contamination. Studies using mouse model of infection
      with a highly virulent Salmonella typhimurium serotype have provided important
      insight into the complexity of the innate immune response to infection. The
      players are numerous but emphasis was placed on the genes that were discovered
      using genetic approaches and in vivo assay with live pathogen and include
      positional cloning of mouse mutations and manipulation of genes in the context of
      whole animal either by transgenesis or knockout technologies. Some of the
      critical genes include those known to play a role in the detection of the
      bacteria (Cd14, Lbp, Tlr4 and Tlr5) and in microbicidal activity (Slc11a1, Nos2,
      NADPH oxidase and cryptdins). These discoveries have already initiated the search
      for the contribution of particular genetic pathways in the innate immune response
      of humans to infection with Salmonella and other intracellular microorganisms.

PMID- 15581468
TI  - [Origin of resistance to Imatinib mesylate: lessons learned from this
      experience].
AB  - For drug development and pharmaceutical research, targeting the molecular
      abnormalities is considered as a new challenge. A number of diseases including
      cancer are linked to perturbation of tyrosine kinase (TK). Imatinib (Glivec or
      Gleevec, Novartis), the most potent inhibitor of c-abl TK, was recently
      developed. This molecule has been approved in the treatment of chronic myeloid
      leukemia (CML). However, emergence of clinical resistance regarding a low rate of
      CML patients leads to intensive research. In the current article, we discuss the
      data and the mechanism of the resistance phenomenon. This review illustrates the
      important requirement to transfer back the information from patient to laboratory
      in order to improve future drug design.

PMID- 15581469
TI  - [Alcohol dependence and polymorphisms of serotonin-related genes].
AB  - Genetic factors have a non-specific but significant impact on the risk of alcohol
      dependence. Molecular genetic analyses are now less devoted to the genes involved
      in the metabolism of ethanol, focusing on core concepts of addiction, such as
      arousal, pleasure, reward, craving, and impulsivity. Indeed, the neuro-cognitive
      functions, temperament traits and psycho-behavioral specificities of patients
      with alcohol abuse or dependence led to select new sets of candidate genes. One
      of them are related to serotonin transmission, as serotonin modulates
      dopaminergic pathways, and is also stimulated by many addictive susbtances. The
      genetic analyses of serotonin in alcohol-dependence are mainly focused on the
      serotonin transporter gene (5-HTT), as one polymorphism within the promoter has a
      functional impact. From the 16 case-control association studies yet performed,
      many are positive, and one family-based study showed a large excess of
      transmission of the short allele. We performed a meta-analysis of the case
      control studies showing that the S allele could be a risk factor for a phenotype
      related to alcohol-dependence (OR=1.31), with still unknown boundaries. Other
      genes coding for serotonin receptors were analysed with mainly negative results,
      for example the 5-HT2A, 5-HT2C, 5-HT5A and 5-HT7 receptors. The 5-HT1B could be
      more interesting as being located in a locus linked to alcohol preference in
      rodents, and associated with antisocial alcoholism in two human studies. Genetics
      may thus provide new insights about the different mechanisms which explain why
      some subjects are more at risk for the development of alcohol abuse or
      dependence. Genes involved in the transmission, reuptake and metabolism of
      serotonin constitute a set of candidate genes that could be involved in core
      aspects of alcoholism, such as the tendency to prefer immediate reward, despite
      negative consequences.

PMID- 15581470
TI  - [Alcohol dependence, temper and personality].
AB  - This review focuses on classical and recent research work in the field of alcohol
      dependence. Data from psychopathological studies trying to determine a "pre
      addictive" personality are exposed. More recent studies assess personality
      disorders and dimensions of temperament associated to alcohol dependence.
      Sensation seeking, antisocial personality and novelty seeking appear as the main
      psychological parameters involved in dependence. Sensation seeking is a dimension
      of personality often associated to behavioral dependence. Sensation seeking is
      assessed with a five-component scale including general factor, thrill and
      adventure seeking, experience-seeking, disinhibition, and boredom susceptibility.
      Patients presenting alcohol dependence have a higher level of sensation seeking.
      Neurophysiological and genetic studies try to correlate these personality
      features to biological parameters. Preliminary results of these works are
      presented and discussed.

PMID- 15581471
TI  - [Free anonymous screening consultation and clinical management of HIV infection].
AB  - In France, since 1988, anonymous and free consultations (called CDAG) have been
      settled in the country to facilitate an individual and volunteer approach for HIV
      screening. At the time, there are more than 380 CDAG with newly defined
      objectives. CDAG are supposed to encourage early screening, facilitate access to
      precarious persons and persons at risk for sexually transmitted diseases, and
      reinforce prevention, helping consultants to define a personal preventive
      strategy. CDAG are also supposed to play a role in prevention of both hepatitis B
      and C, and syphilis. They may help to link screening and healthcare. Their
      activity is increasing and the rate of positive test is twice that of private
      laboratories. Patients consulting those facilities are younger and more at risk
      than general population. Between 1000 and 2000 HIV positive tests are detected in
      CDAG each year (11 % of positive tests in the country). The real impact on
      prevention and screening at the national level is unknown, in part because of
      anonymity. To improve the characterization of consultants, data collection will
      be modified in 2004, and a network of selected and volunteer centres will collect
      continuously more accurate data.

PMID- 15581472
TI  - [Zoom on the excellence of biomedical research in France].
AB  - Among the key benchmarks in assessing research excellence is the production and
      recognition of scientific discoveries for innovation. Despite the growing use of
      bibliometric indicators for policy-making purposes, there is still no consensus
      concerning the appropriate measures of research excellence. In this study, we
      examine the performance of France in biomedical sciences using several ISI-based
      indicators. We focus on the results provided by these two selective indicators:
      the absolute numbers and proportion of papers published in the very high-impact
      journals (above 20) and in the 1 % of the most highly cited papers. Furthermore,
      we present the detailed analysis of the Top 1 % French biomedical articles. On
      this basis we identify the crucial fields, the most active centres per speciality
      and the networks and the degree of international collaboration resulting from
      different types of research. These results provide an objective demonstration
      that the French biomedical research meets with high international standards and
      contributes to the world core research.

PMID- 15581473
TI  - [Death-tag].

PMID- 15581474
TI  - [Back from the States General of Research conference in Grenoble].

PMID- 15581475
TI  - [A miraculous cave].

PMID- 15581476
TI  - [An opening in Duchenne muscular dystrophy: persistent therapeutic rescue of
      dystrophin by vectorized antisense mediated exon skipping in mdx mice].

PMID- 15581478
TI  - New apoptosis cascade mediated by lysosomal enzyme and its protection by epigallo
      catechin gallate.
AB  - We found a novel procaspase-3 activating cascade mediated by lysosomal enzyme.
      The activating enzyme of procaspase-3, named lysoapoptase having the molecular
      weight of 78kDa was determined to be a lactoferrin located in the lysosome.
      Recombinant lactoferrin accelerated the processing of procaspase-3 to form active
      caspase-3 in vitro. D-Galactosamine is a well-known inducer of hepatocyte
      apoptosis. The caspase-3 which plays a common central role in the final step of
      various apoptosis cascades, was dramatically increased in the cytoplasm by the d
      galactosamine administration in vivo. When D-galactosamine was administrated as a
      death signal in vivo, the lysosomal lactoferrin was released into the cytoplasm
      and procaspase-3 located in the cytoplasm was processed to form active caspase-3.
      The cotreatment of epigallo-catechin gallate resulted in the complete protection
      of the hepatocyte apoptosis suppressing the increases of caspase-3 in the
      cytoplasm. The caspase-3 activity was also inhibited directly by the epigallo
      catechin gallate. Therefore, all apoptosis cascades mediated by caspase-3 should
      be suppressed by epigallo-catechin gallate. The caspase-3 activity was not only
      directly inhibited by epigallo-catechin gallate in vitro, but the release of
      lactoferrin from the lysosomes into the cytoplasm was also suppressed by epigallo
      catechin gallate treatment in vivo. Therefore, the apoptosis induction was
      suppressed at the two successive steps by cotreatment of epigallo-catechin
      gallate in vivo.

PMID- 15581479
TI  - Gemcitabine-induced apoptosis in a drug-resistant mouse leukemia L1210 cell line
      that does not express p53.

PMID- 15581480
TI  - Significance of enzyme degradation rate and enzyme inhibition in targeted
      chemotherapy.

PMID- 15581481
TI  - Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a
      genetic screen and effects on catalysis by the recombinant proteins.

PMID- 15581482
TI  - Significance of subnuclear localization of key players of inositol lipid cycle.

PMID- 15581483
TI  - Regulation of enzyme activity in vivo is determined by its cellular localization.

PMID- 15581484
TI  - The prolyl hydroxylase enzymes that act as oxygen sensors regulating destruction
      of hypoxia-inducible factor alpha.

PMID- 15581485
TI  - Hypoxia in tumors: molecular targets for anti-cancer therapeutics.

PMID- 15581486
TI  - Mechanisms responsible for regulation of pyruvate dehydrogenase kinase 4 gene
      expression.

PMID- 15581487
TI  - Regulation of the regulatory enzyme, 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase.

PMID- 15581488
TI  - New roles for lamins, nuclear envelope proteins and actin in the nucleus.

PMID- 15581489
TI  - Phosphatidylcholine biosynthesis inside the nucleus: is it involved in regulating
      cell proliferation?

PMID- 15581490
TI  - Functional implications of the diacylglycerol kinase family.

PMID- 15581491
TI  - Phosphatidylinositol transfer protein function in the mouse.

PMID- 15581492
TI  - Cross-talks between nucleotide receptor-induced signaling pathways in serum
      deprived and non-starved glioma C6 cells.

PMID- 15581493
TI  - Integration of protein kinase signaling pathways in cardiac myocytes: signaling
      to and from the extracellular signal-regulated kinases.

PMID- 15581494
TI  - Regulation of phospholipase D2 by GTP-dependent interaction with dynamin.

PMID- 15581495
TI  - Cell signaling by a physiologically reversible inositol phosphate
      kinase/phosphatase.

PMID- 15581496
TI  - The role of phosphoinositides and phosphorylation in regulation of NADPH oxidase.

PMID- 15581497
TI  - Phosphoinositide 3-kinase gamma mediates Jun kinase activation via its lipid
      kinase activity.

PMID- 15581498
TI  - Critical role of cathepsin-inhibitors for autoantigen processing and
      autoimmunity.

PMID- 15581499
TI  - Methylation demand and homocysteine metabolism.

PMID- 15581500
TI  - Protection against electrophile and oxidative stress by induction of phase 2
      genes: the quest for the elusive sensor that responds to inducers.

PMID- 15581501
TI  - The variability in the interval between estrus and ovulation in cattle and its
      determinants.
AB  - Fertility of Holstein cows has been decreasing for years and, to a lesser extent,
      the fertility of heifers too but more recently. A hypothesis to explain this
      phenomenon may be that the chronology of events leading to ovulation is different
      for those animals bred nowadays when compared to what was reported previously;
      this would result in an inappropriate time of insemination. Therefore, two
      experiments were designed to investigate the relationships among estrus behavior,
      follicular growth, hormonal events and time of ovulation in Holstein cows and
      heifers. In the first experiment, the onset of estrus, follicular growth,
      patterns of estradiol-17beta, progesterone and LH, and the time of ovulation were
      studied in 12 cyclic Holstein heifers that had their estrus synchronized using
      the Crestar method; this was done twice, 3 weeks apart. The intervals between
      estrus and ovulation, estrus and the LH peak, and between the LH peak and
      ovulation were, respectively, 38.5 h +/-3.0, 9.1 +/- 2.0 and 29.4 h +/-1.5
      (mean+/- S.E.M). The variation in the interval between estrus and the LH peak
      explained 80.6% of the variation in the interval between estrus and ovulation.
      The intervals between estrus and the LH peak, and estrus and ovulation were
      correlated with estradiol-17beta peak value (r=-0.423, P <0.04 and r=-0.467,
      P<0.02, respectively). Positive correlation coefficients for the number of
      follicle larger than 5 mm, and negative correlation coefficients for the size of
      the preovulatory follicle with the intervals between estrus and LH peak, LH peak
      and ovulation, and estrus and ovulation suggest an ovarian control of these
      intervals. In respect to its role to explain the variation in the interval
      between estrus and ovulation, the variation in the interval between estrus and
      the LH peak was evaluated further in a second set of experiments utilizing 12
      pubertal Holstein heifers and 35 Holstein cows. The duration of the interval
      between the beginning of estrus and the LH peak was longer in heifers than in
      cows (4.15 h versus -1.0 h; P <0.002); the variation for this interval was higher
      in cows than in heifers (S.E.M.= 1.2 h versus 0.8 h; P=0.01). According to the
      results of these studies it can be proposed that estradiol and other product(s)
      of ovarian origin regulate not only the duration of intervals between the onset
      of estrus and the LH surge but also between the LH surge and ovulation. From the
      results obtained in the first experiment, it may be postulated that differences
      observed between cows and heifers for the duration of the interval between onset
      of estrus and the LH surge as well as for the variation of this interval would be
      observed also for the interval between the onset of estrus and ovulation.
      Therefore, on a practical point of view, the long interval between the onset of
      estrus and ovulation and the high variation of this interval, especially in cows,
      may be a source of low fertility and should be considered when analysing
      reproductive disorders.

PMID- 15581502
TI  - Use of RAPD markers for identifying Nelore bulls with early reproductive
      maturation onset.
AB  - Random amplified polymorphic DNA (RAPD) markers were used for identifying animals
      with early (precocious) or late (non-precocious) reproductive maturation onset.
      Animals (n=34) were phenotyped according to spermatozoa appearance in ejaculates
      (group A, 20 animals) or to the expected progeny difference (EPD) values for
      scrotal circumference (group B, 14 animals). The RAPD markers were initially
      detected by amplifying two pooled samples of equimolar amounts of DNA from the
      eight precocious 12 and non-precocious animals of group A. Only 38 out of 320
      random primers used for screening group A pooled samples detected polymorphisms.
      These polymorphic primers generated 443 distinguishable and reproducible bands,
      from which 174 were polymorphic and 269, monomorphic. These polymorphic primers
      were then used in RAPD reactions to amplify individual DNA samples from animals
      belonging to both groups, A and B. The dendrograms generated from RAPD patterns
      allowed phenotypic class differentiation in both cases. Therefore, RAPD markers
      can be used as a tool for identifying genotypes favoring early sexual maturation
      in Nelore breeding programs.

PMID- 15581503
TI  - A case of freemartin with atresia recti and ani in Japanese Black calf.
AB  - A female Japanese Black calf was born on 25 March 2003 at Hiroshima University
      Farm as a co-twin to a male Japanese Black calf. The male calf showed no external
      urogenital abnormalities. The absence of anal opening and external features of
      freemartinism were observed in the female. A small opening to the vulva (about
      1.5 cm in length) with fused lips and a prominent clitoris were seen. The hair
      around the vulva was 3.5 cm in length and was heavy and dense. The distance from
      the vulva to the atretic anus was 9.0 cm. There were no other detectable
      abnormalities on physical examination. The PCR-based DNA test showed male
      specific sequences confirming the calf to be freemartin. At autopsy 1 day after
      the calf birth, the gonads were found to be small and hard and the left uterine
      horn showed segmental aplasia near its proximal end. Two seminal glands (remnants
      of mesonephric duct) were located on both sides of the uterine body. A cervix was
      absent. The vagina was underdeveloped and looked like a tubual structure. The
      rectal end was closed, while the distance from the end of the atretic rectum to
      the absent anal opening was about 4.0 cm. On histological examination, the gonads
      exhibited extensive morphologic alteration; there was no cortex with the absence
      of ovarian structures. The seminal glands consisted of hypoplastic glandular
      tissue surrounded by extensive fibrous connective tissue. In conclusion, this is
      a case report of a freemartin with atresia recti and ani.

PMID- 15581504
TI  - Implementation of flow cytometry for quality control in four Danish bull studs.
AB  - A flow cytometric method for simultaneous determination of sperm concentration
      and viability has recently been developed. In 2001, four Danish bull studs
      purchased flow cytometers and eight technicians were trained for routine analysis
      of raw and frozen-thawed semen. After initial training of the technicians, an
      experiment was carried out to document the precision of the system. The aim was
      also to assess if flow cytometric determination of sperm concentration could
      result in a more uniform production of semen doses. Results of this experiment
      showed high precision in the determination of sperm concentration and
      coefficients of variation were 3.5 and 2.4% for raw and frozen-thawed semen,
      respectively. Sperm viability was also assessed with high precision and
      coefficients of variation were 0.9% for raw semen and 1.7% for frozen-thawed
      semen. Furthermore, the experiment showed that package of semen doses after flow
      cytometric determination of sperm concentration in the raw semen results in a
      significantly smaller variation in the number of sperm per dose. In the second
      experiment, frozen semen was exchanged between the participating studs and were
      analysed by flow cytometry as well as by microscopic assessments by the eight
      technicians. Results show that the average correlation between technicians were
      0.38 for motility assessments while flow cytometric agreement between technicians
      was significantly higher (average correlation was 0.86 for sperm viability and
      0.92 for sperm concentration). The experiment also showed very high agreements
      between assessments within lab technician (correlations r=0.98 (sperm
      concentration) and r=0.99 (sperm viability)). Experiment 3 revealed that straws
      from the same batch varies in both concentration and viability. It is concluded
      that flow cytometric determination of sperm concentration and viability can be
      used to improve semen assessment by AI studs and result in a better quality
      control.

PMID- 15581505
TI  - Fertility response of yearling beef heifers after prebreeding energy
      manipulation, estrous synchronization and timed artificial insemination.
AB  - The effect of dietary energy and weight class on the fertility of yearling beef
      heifers (Angus, Hereford, and Angus x Hereford) was investigated over 2 years. In
      year 1, heifers (n=58) were classed as heavy (HW; > or =340 kg) or light weight
      (LW; <340kg) and then assigned to receive either a low (LE; 0.23 kg/day) or high
      energy (HE; 0.68 kg/day) diet. In year 2, heifers (n=60) were also classified as
      heavy (> or =335kg) or light weight (<335 kg), but the energy content of the diet
      was raised so that heifers on the LE and HE were targeted to gain 0.46 and 0.79
      kg/day, respectively. Heifers in the four groups, LELW (n=14 and 12), LEHW (n=16
      and 17), HELW (n=13 and 15), and HEHW (n=15 and 16) received restricted amounts
      of concentrate (HE > LE) and free choice hay over 47 or 42 days (year 1 and year
      2, respectively). To synchronize estrus, heifers were fed capsules containing MGA
      (0.5 mg/animal each day) beginning 11 days before the end of the feeding trial
      (day 0), PGF(2alpha) (25mg i.m.) and estradiol benzoate (Ebeta; 400 microg i.m.)
      was given on days 8 and 10, respectively. Estrous behavior was observed (days 10
      and 11) and all heifers were inseminated on day 11. Following AI, heifers were re
      grouped and a bull was introduced (days 27-39) for the second service in both
      years. Pregnancy diagnosis for the first (days 41-42) and second services (days
      69-97) was performed by transrectal ultrasonography. Transrectal ultrasonic
      observations of ovarian follicle number and size were completed for a subset of
      heifers (n=5-8) from each experimental group at the end of the feeding trial. The
      effect of year was not significant for any of the reproductive performance
      variables measured. The mean ADG was (0.72 +/- 0.04 kg/day) and was greater in LW
      than HW heifers and in heifers in the HE than LE treatment groups (P <0.05). In
      heifers receiving the LE diet, ADG was lower in HW than LW heifers (weight x
      diet; P=0.02; 0.54 +/- 0.04 and 0.62 +/- 0.03 kg/day for HW and LW heifers,
      respectively). The diameter of the largest follicle was greater in heifers
      receiving the HE diet (P < 0.05; 11.3 +/- 0.4 mm) than those on the LE diet (10.3
      +/- 0.3), and in LW (P <0.05) compared to HW heifers. The HE diet increased the
      size of the largest follicle in LW but not HW heifers (diet x weight, P <0.05).
      The percentage of pubertal heifers at the end of the feeding period (59.3%),
      estrous response (56.4%), conception rate (47.7%), ovulation rate (88.9%), and
      first service pregnancy rate (36.2%) were not significantly affected by initial
      weight or diet. There was a tendency for first service pregnancy rates to be
      greater in LW than HW heifers consuming the LE diet (diet x weight, P <0.1; 54.2
      +/- 15 and 30.3 +/- 10% for LELW and LEHW heifers, respectively). Pregnancy rate
      after two services was greater (P=0.01) in LW (82 +/- 10%) than in HW (64.5 +/-
      10%). The LE diet achieved moderate rates of gain and allowed high level of
      reproductive performance in LW but not HW heifers.

PMID- 15581506
TI  - Observations on the reproductive effects of once or twice weekly injections for 6
      weeks of the GnRH agonist deslorelin in the cow.
AB  - This study investigated the reproductive effects in Holstein-Friesian cows of
      once or twice weekly intramuscular injection for 6 weeks of 100 microg of the
      GnRH agonist deslorelin at intervals. Oestrus was synchronized in non-lactating
      Holstein-Friesian cows before they were allocated randomly to receive either 100
      microg deslorelin once weekly (D1; N=10) or twice weekly (D2; N=8) or acted as
      untreated controls (CON; N=8). The first injection was given on day 6 post
      oestrus and the last injection on day 48 post-oestrus. Blood samples were
      collected twice weekly from each cow until day 76 after the synchronized oestrus
      to profile plasma P4. A single injection of prostaglandin was administered to all
      cows on day 20 post-oestrus to ensure luteolysis occurred. Ovaries were examined
      twice weekly by transrectal ultrasonography and then subsequently at weekly
      intervals to monitor ovarian structures. Progesterone profiles observed over two
      complete cycles for CON cows were typical of those expected for cows displaying
      regular oestrous cycles. Injection of deslorelin on day 6 post-oestrus induced
      ovulation in 100% (18/18; D1 and D2) of deslorelin-treated cows. Three categories
      of responses based on plasma P4 profiles were defined amongst the deslorelin
      treated cows. Complete anoestrus was observed in 20% (2/10) of D1 and 63% (5/8)
      of D2 cows. A partial response characterised by intermittently low concentrations
      of P4 was observed in 50% (5/10) of D1 and 25% (2/8) of D2. A complete lack of
      response to deslorelin, with P4 profiles indistinguishable from CON cows, was
      seen in 30% (3/10) of D1 and 13% (1/8) of D2 cows. When results from D1 and D2
      were pooled, a greater proportion of deslorelin-treated cows had abnormal ovarian
      cycles during the treatment period (56% versus 0%; D1 and D2 versus CON, P
      <0.001). In conclusion, the repeated injection of deslorelin either once or twice
      weekly for 6 weeks significantly altered the ovarian cycles of some cows;
      individual cow responses observed varied widely and ranged from complete
      anoestrus to a cycle indistinguishable from normal.

PMID- 15581507
TI  - Nitric oxide-induced capacitation of cryopreserved bull spermatozoa and
      assessment of participating regulatory pathways.
AB  - The effect of nitric oxide (NO*) on the capacitation rates of cryopreserved bull
      spermatozoa and the participation of protein kinases in the capacitation process
      were evaluated. A pool of spermatozoa from four bulls were incubated in TALP
      medium in the presence of heparin (10 IU/ml) or sodium nitroprusside (SNP, 0.05
      100 microM), a NO* donor. The participation of NO* was confirmed by the use of
      scavengers, i.e. methylene blue (50,100 microM) and hemoglobin (20-40 microg/ml).
      The role of nitric oxide synthase in heparin-induced capacitation was evaluated
      using enzyme inhibitors Nomega-nitro-L-arginine methyl ester (L-NAME) and Nomega
      nitro-L-arginine (L-NA) in concentrations ranging from 1 to 500 microM. The
      effects of protein kinase A (PKA), protein kinase C (PKC) and protein tyrosine
      kinase (PTK), on NO*-induced capacitation were evaluated by incubation with
      specific inhibitors of these enzymes (H-89, 50 microM; bisindolylmaleimide I, 0.1
      microM and genistein, 3 microM). The role of hydrogen peroxide or superoxide
      anion in NO*-induced capacitation was evaluated by incubation with catalase (20
      100 microg/ml) or superoxide dismutase (SOD, 0.05-0.5 mg/ml), respectively.
      Capacitation percentages were determined by the fluorescence technique with
      chlortetracycline (CTC). SNP concentrations employed had no effect on progressive
      motility or sperm viability. Capacitation values of the 0.05 microM SNP treatment
      (31 +/- 5.15%) were similar to those of heparin treated samples (33 +/- 4.27%).
      Inhibitors of nitric oxide synthase (NOS) diminished capacitation percentages in
      a dose-dependent manner as did the addition of NO*- scavengers (P <0.05). The
      presence of PKA, PKC and PTK inhibitors likewise decreased capacitation
      percentages (6.25 +/- 0.71, 12.75 +/- 1.41, 9.00 +/- 1.41%, respectively). The
      presence of catalase or SOD in the incubation medium had no effect on
      capacitation percentages. These results indicate that NO* may be generated by a
      sperm NOS during heparin-induced capacitation and that exogenous NO* acts as a
      capacitation inducer and involves the participation of PKA, PKC and PTK as part
      of the intracellular mechanisms that lead to capacitation in cryopreserved bull
      spermatozoa.

PMID- 15581508
TI  - Effects of steroidal glycoalkaloids from potatoes (Solanum tuberosum) on in vitro
      bovine embryo development.
AB  - alpha-Solanine and alpha-chaconine are two naturally occurring steroidal
      glycoalkaloids in potatoes (Solanum tuberosum), and solanidine-N-oxide is a
      corresponding steroidal aglycone. The objective of this research was to screen
      potential cyto-toxicity of these potato glycoalkaloids using bovine oocyte
      maturation, in vitro fertilization techniques and subsequent embryonic
      development as the in vitro model. A randomized complete block design with four
      in vitro oocyte maturation (IVM) treatments (Experiment 1) and four in vitro
      embryo culture (IVC) treatments (Experiment 2) was used. In Experiment 1, bovine
      oocytes (n=2506) were matured in vitro in medium supplemented with 6 microM of
      alpha-solanine, alpha-chaconine, solanidine-N-oxide or IVM medium only. The in
      vitro matured oocytes were then subject to routine IVF and IVC procedures.
      Results indicated that exposure of bovine oocytes to the steroidal glycoalkaloids
      during in vitro maturation inhibited subsequent pre-implantation embryo
      development. Potency of the embryo-toxicity varied between these steroidal
      glycoalkaloids. In Experiment 2, IVM/IVF derived bovine embryos (n=2370) were
      cultured in vitro in medium supplemented with 6 microM of alpha-solanine, alpha
      chaconine, solanidine-N-oxide or IVC medium only. The results showed that the pre
      implantation embryo development is inhibited by exposure to these glycoalkaloids.
      This effect is significant during the later pre-implantation embryo development
      period as indicated by fewer numbers of expanded and hatched blastocysts produced
      in the media containing these alkaloids. Therefore, we conclude that in vitro
      exposure of oocytes and fertilized ova to the steroidal glycoalkaloids from
      potatoes inhibits pre-implantation embryo development. Furthermore, we suggest
      that ingestion of Solanum species containing toxic amounts of glycoalkaloids may
      have negative effects on pre-implantation embryonic survival.

PMID- 15581509
TI  - Influence of age on the relationship between annual changes in horn growth rate
      and prolactin secretion in the European mouflon (Ovis gmelini musimon).
AB  - Annual variations in the growth of horns, and their correlation with seasonal
      changes of testicular size, and prolactin (PRL) and melatonin secretion were
      monitored in six pubertal mouflon rams living in their original latitude (40
      degrees N). Mouflons born and maintained under captive conditions were classified
      in two age classes: sub-adult (2 years; n=3) and adult (> or =3 years; n=3). The
      rate of horn growth was greater (P <0.001) in sub-adult than in adult mouflon
      rams. Horn growth was influenced by season in both adult and sub-adult mouflons
      (P <0.05) with largest monthly growth occurring in spring and summer. Seasonal
      variations of plasma PRL concentrations were correlated with horn growth in
      adult, but not in sub-adult mouflon rams. The rate of horn growth was inversely
      correlated with testicular size (r=-0.5, P=0.07). Seasonal changes in the
      amplitude of the daily melatonin rhythm in solstices and equinoxes were observed,
      which were not correlated with variations in the rate of horn growth. These
      results provide support for a possible role of PRL in the control of growth of
      horns in the adult mouflon.

PMID- 15581510
TI  - Morphometry of ovarian structures by transrectal ultrasonography in Serrana
      goats.
AB  - The accuracy of transrectal real-time ultrasonography (RTU) scanning technique to
      detect ovarian structures (follicles and corpus luteum) of Serrana goats was
      compared to the data obtained by observation of ovarian sequential slices. This
      slicing technique (SLI) was considered as reference method. The laparoscopy and
      laparotomy techniques were also used for corpora lutea identification. For this
      purpose the ovaries of 14 females were observed, 7-8 days after ovulation, by
      transrectal ultrasonography followed by laparoscopic examination. Then ovaries
      were removed and studied by slicing. In the sliced sections of each ovary (n=28),
      follicles and corpus luteum (CL) were identified and counted. CL and follicular
      diameters were measured using a millimetre scale. The total number of follicles,
      counted by RTU, was significantly lower than that observed by SLI (P <0.01). This
      difference was mainly due to the under estimation of <2 mm follicles category.
      The correlation coefficient between category data obtained by RTU and SLI methods
      for the number of follicles > or =3 mm was high (r2=0.95, P <0.001), which
      highlights the use of UTR as a potential methodology to study the follicular
      dynamic of goats. There were no significant differences (P >0.05) between the
      average number (mean +/- S.D.) of corpus luteum identified per ovary by RTU (0.71
      +/- 0.75), laparoscopy (0.58 +/- 0.71), laparotomy (0.67 +/- 0.76) or SLI (0.83
      +/- 0.76) methods. The accuracy for the identification of ovulation, validated by
      CL detection on D7-D8 by SLI (100%), was 91.7%, 87.5% and 83.3% by RTU,
      laparotomy and laparoscopy, respectively. The negative predictive value of RTU,
      laparotomy and laparoscopy to verify the absence of a CL in the ovary was 81.8%,
      75.0% and 69.2%, respectively. The specificity of all three methods for the CL
      identification was 100%. No significant differences (P >0.05) were found in the
      probability to detect the exact number of CL (0, 1 or 2) counted in each ovary
      between the RTU (87.5%), laparotomy (83.3%) and laparoscopy (75.0%) methods when
      compared with the reference method. The diameter of spherical CL could be
      estimated with reliability (r2=0.86; P <0.001). The real-time ultrasonographic
      scanning proved to be a highly accurate method for detection and measurement of
      several categories of follicles and CL size in Serrana goats. The results of the
      present study show that laparoscopy and RTU are similarly reliable techniques for
      CL detection. However, the RTU represents a non-traumatic technique with
      advantages to animal welfare both in experimental and reproductive evaluation of
      the size of ovarian structures.

PMID- 15581511
TI  - Piglets born after non-surgical deep intrauterine transfer of vitrified
      blastocysts in gilts.
AB  - The aims of this study were: (1) to evaluate the effect of the number of previous
      estrus of recipient gilts on effectiveness of intrauterine insertion of a
      flexible catheter designed for non-surgical deep intrauterine catheterization
      during diestrus in pigs; and (2) to determine the farrowing rate and the litter
      size after non-surgical deep intrauterine embryo transfer (ET) of porcine
      blastocysts vitrified by the open pulled straw (OPS) method. In experiment 1, 27
      large white hyperprolific gilts (LWh) with 2-6 previous estrus were used.
      Intrauterine insertions of the flexible catheter were carried out at day 5.5-6 of
      the estrous cycle (D0=onset of estrus). During insertions, no or only moderate
      reactions were observed in 88.9% of gilts and was not related (P >0.05) to the
      number of estrus prior to the insertion periods. The number of the estrus had a
      significant effect (P <0.05) on the difficulties found during the procedure. In
      the 100% of gilts with two estrus (N=6) it was not possible to insert the
      flexible catheter through the cervix. In gilts with three or more estrus, it was
      possible to pass the cervix and to progress along a uterine horn in 80.9% of the
      cases. In 86.7% of the gilts, the tip of the flexible catheter achieved the
      second or third quarter of the uterine horn. In experiment 2, following non
      surgical deep intrauterine transfer of 20 vitrified/warmed blastocysts, 9 Meishan
      recipients (42.9%) farrowed an average of 5.4 +/- 0.8 piglets (range 3-9) of
      which 0.6 +/- 0.3 piglets (range 0-2) were born dead. In conclusion, this study
      shows that it is possible to obtain birth of piglets following non-surgical deep
      intrauterine embryo transfer (ET) of vitrified/warmed blastocysts. Non-surgical
      deep intrauterine ET and OPS vitrification methods are promising procedures to be
      used together for the introduction of new genetic material in a farm.

PMID- 15581512
TI  - Effect of oviductal and cumulus cells on zona pellucida and cortical granules of
      porcine oocytes fertilized in vitro with epididymal spermatozoa.
AB  - The objective of this study was to evaluate the effects of porcine oviductal
      epithelial cell (POEC) monolayers and cumulus cells on the zona pellucida (ZP)
      and cortical granules (CG) of in vitro matured porcine oocytes. Denuded and
      cumulus-enclosed oocytes were exposed to POEC before or during in vitro
      fertilization (IVF). The functional effects of the co-culture system were the
      tested on the ZP resistance, measured by the time necessary to dissolve the ZP
      with 0.1% pronase, and the distribution and density of the cortical granules. CG
      density in the equator and cortex of each oocyte was evaluated by confocal
      microscopy after staining with fluorescein isothiocyanate-labelled peanut
      agglutinin (FITC-PNA). Both variables were assessed immediately after an in vitro
      maturation period (IVM group), 3 and 6h after culture with or without (Control)
      oviductal cells (Experiment 1) and 3h after insemination with frozen-thawed
      epididymal spermatozoa in the presence or absence (Control) of oviductal cells
      (Experiment 2). The time to dissolve the ZP of oocytes from IVM group was 440.4
      +/- 61.7 s and no difference was observed among groups in Experiment 1. In
      contrast, the density of CG was affected; oocytes pre-incubated for 6h had a
      higher density than those pre-incubated for 3 h (P <0.001). Oocytes fertilized in
      vitro in the presence of POEC (Experiment 2) had a similar ZP digestion time as
      control oocytes 3 h after insemination. The presence of POEC during IVF as well
      as the presence of cumulus cells had no effect on the density and distribution of
      CG. However, a significant decrease in the density of CG was observed in the
      fertilized oocytes compared to in vitro matured oocytes (P <0.001). It is
      concluded that under the conditions employed the oviductal and cumulus cells in
      the perifertilization period had no effect on ZP hardening and CG density.
      However, an increase in CG density was observed when oocytes were maintained in
      culture. In addition, no hardening of ZP was observed after IVF, and denuded and
      cumulus-enclosed oocytes showed similar cortical reactions after insemination
      with epididymal spermatozoa regardless of the presence of POEC.

PMID- 15581513
TI  - Embryonic and fetal development in a commercial dam-line genotype.
AB  - During depopulation of a breeding unit within Swine Graphics Enterprises,
      extensive data were collected and used to examine relationships among ovulation
      rate, the pattern of prenatal loss, and placental and fetal development. Groups
      of Large White x Landrace females (n=447) were slaughtered between day 20-30, 50
      55 or 85-90 of gestation, with approximately equal numbers of animals
      representing gilts and parity 1 (G/P1), parity 2-3 (P2/3), and parity >4 (P4+).
      Ovulation rate and embryo number were recorded for all animals. With the
      exception of the G/P1 animals, embryonic and placental weight were recorded for
      four conceptuses per sow on day 20-30; on day 85-90 two conceptuses per sow were
      dissected to determine placental and fetal development. Ovulation rate (22.7 +/-
      0.2 overall) was higher (P <0.05) in P2/3 (23.6 +/- 0.4) and P4+ (24.7 +/- 0.4)
      than in G/P1 (20.2 +/- 0.5). Embryonic/fetal survival was 61.8 +/- 2.1% at day 20
      30, 50.2 +/- 2.2% at day 50-55 and 48.7 +/- 1.9% at day 85-90 and the number of
      surviving conceptuses was higher (P <0.05) in the P2/3 sows than in other parity
      groups. There was no relationship between ovulation rate and number of live
      embryos at day 20-30 or 85-90. At day 20-30 and 85-90, embryo weight was
      positively correlated with placental weight, but neither placental weight nor
      embryonic/fetal weight was correlated with number of viable embryos. A parity by
      gestation day interaction existed; placental weight for P4+ (3.42 +/- 0.43 g) was
      less than for P2/3 (7.55 +/- 0.40 g) at day 20-30 (P <0.0001), whereas at day 85
      90, placental weight of P2/3 (209.5 +/- 8.5 g) was less (P=0.05) than both G/P1
      (235.7 +/- 7.3g) and P4+ (235.4 +/- 7.1 g). At day 85-90, fetal brain weight,
      relative to body weight (R2=0.61, P <0.0001), and fetal brain:liver weight ratio
      (R2=0.35; P <0.0001) were negatively related to mean fetal weight, and
      brain:liver weight ratio showed a trend towards a relationship with number of
      viable fetuses (P=0.08). Parity also affected brain:liver weight ratio (P=0.01).
      Clearly, high ovulation rates in the higher parity sows have the potential to
      cause excessive in utero crowding of conceptuses in the post-implantation period.
      Even with moderate crowding, increased brain:liver weight ratios in smaller
      fetuses in late gestation indicate that uterine capacity impacts fetal
      development as well as the number of surviving fetuses.

PMID- 15581514
TI  - Improvement of stored turkey semen quality as a result of He-Ne laser
      irradiation.
AB  - Two experiments were carried out to evaluate the effects of He-Ne laser
      irradiation at various energy doses on the quality of stored turkey semen. Four
      semen pools were used in Experiment 1. Each pool was divided into 10 aliquots,
      nine of which were irradiated with energy doses ranging from 0.144 to 10.8 J/cm2
      while the tenth one was not irradiated (control). Each sample was evaluated for
      motility immediately after irradiation, 24 and 48 h later. Energy doses ranging
      from 3.24 to 5.4 J/cm2 had higher (P <0.01) sperm motility index (SMI) value
      compared to the control and samples irradiated with lower and higher laser doses.
      The energy dose of 3.96 J/cm2 was selected for Experiment 2 to obtain further
      insight on its effects on turkey sperm preservation for up to 60 h. Each pool of
      four semen was divided into two aliquots: one represented the control and the
      other one was irradiated with He-Ne laser at an energy dose of 3.96 J/cm2. Each
      sample was evaluated for motility and viability immediately after irradiation and
      then at 12 h intervals up to 60 h. The cell energy charge was also measured by
      HPLC. Exposure to 3.96 J/cm2 increased the SMI and viability of turkey semen
      stored for 60 h compared to the control (P <0.05). The cell energy charge of
      irradiated samples was 200% higher than in the control. Laser irradiation
      increased the longevity of stored turkey spermatozoa, and might be a useful
      technique to enhance semen quality in long-term storage.

PMID- 15581515
TI  - Reproductive behaviour of captive Sumatran rhinoceros (Dicerorhinus sumatrensis).
AB  - The Sumatran rhinoceros (Dicerorhinus sumatrensis) is on the verge of extinction
      in Malaysia. At the Sumatran rhinoceros Conservation Centre in Sungai Dusun, the
      reproductive behaviour of two female and two male rhinoceroses were studied for 8
      10 months during attempts to breed them in captivity. Due to the paucity of
      scientific information on the reproductive biology of the Sumatran rhinoceros,
      this study was conducted to obtain information on the reproductive behaviour of
      this species. The male rhino was introduced to a female rhino in the morning for
      1-2 h daily in order to observe for behavioural oestrus. Observations were made
      on the signs of oestrus and mating behaviour. Oestrus was determined by
      receptivity towards the male and lasted about 24 h. Common signs of oestrus were
      an increase in frequency of urine spraying, tail raising or swinging, anogenital
      and other contacts. Although the males exhibited mounting, the inability of the
      male to achieve intromission was poor. The study demonstrated that the pattern of
      courtship and copulation of the captive Sumatran rhinos were comparable with
      those of other rhino species, reported previously by other scientists and flehmen
      reflex was also exhibited by the male Sumatran rhinos. In a captive breeding
      programme, it is recommended that only an oestral female is introduced into a
      male enclosure due to the male solitary behaviour and to avoid serious injuries
      inflicted onto the females.

PMID- 15581516
TI  - Evaluation of gross anatomical features of cervix of tropical sheep using
      cervical silicone moulds.
AB  - The lambing rate obtained following cervical artificial insemination (AI) with
      frozen semen in sheep is low mainly due to the inability of frozen-thawed sperm
      to traverse the tortuous nature of the cervical canal. Although acceptable
      fertility has been attained by circumventing the cervical barrier through
      laparoscope aided intrauterine AI, the emphasis is currently given on the
      development of alternate non-invasive transcervical AI procedures. The complex
      anatomy of the cervix does not facilitate easy transcervical passage for an
      insemination catheter. The aim of the present study was: (i) to examine the gross
      anatomy of the cervix in slaughtered ewe lambs and adult ewes of the native
      Malpura and Kheri breeds raised under semi-arid tropical environment; and (ii) to
      cast silicone moulds of the reproductive tracts for measuring the dimensions of
      the cervix. Eighty reproductive tracts were excised immediately from carcass of
      Malpura and Kheri ewes and the external os of each one was classified depending
      on their appearance as duckbill, spiral, rosette or flap. The cervical canal of
      each tract was filled with a silicone sealant for casting the mould. Fifty
      complete silicone moulds were obtained representing 25 from ewe lambs and 25 from
      adult ewes. The mean lengths of the cervical mould of ewe lambs and adult ewes
      were 3.8+/-0.12 and 5.3+/-0.15 cm, respectively. The average number of funnel
      shaped folds in the cervical mould of ewe lambs and adult ewes were 3.2+/-0.19
      and 3.4+/-0.22. However, the second and third-folds from the os were observed to
      be accentric in both ewe lambs and adult ewes. The information generated in this
      study would be useful for increasing the success rate of penetration in ewes
      exhibiting estrus in order to improve the lambing rate of tropical ewes following
      transcervical AI.

PMID- 15581517
TI  - Contraceptive use in teens: a threat to bone health?

PMID- 15581518
TI  - Changes in sexual behaviors among high school students.

PMID- 15581520
TI  - The missing psychotic disorders.

PMID- 15581522
TI  - Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density
      in a cohort of adolescent girls.
AB  - PURPOSE: To conduct a longitudinal comparison of bone mineral density (BMD) in
      370 adolescent girls, aged 12-18, who self-selected depot medroxyprogesterone
      acetate (DMPA) or an oral contraceptive (OC) containing 20 microg ethinyl
      estradiol/100 microg levonorgestrel with that in girls who received no hormonal
      treatment (control group). METHODS: Lumbar spine and femoral neck BMD
      measurements were obtained by dual energy x-ray absorptiometry at baseline and 12
      months. Data were analyzed with repeated measures analysis of covariance methods.
      RESULTS: Over 12 months, lumbar spine BMD decreased in the DMPA group (n = 29),
      with a mean percent change of -1.4% (95% confidence interval [CI] -2.73, -0.10),
      and increased by a mean of 3.8% (95% CI 3.11, 4.57) in the control group [n = 107
      (p < .001)]. The increase in mean percent change in lumbar spine BMD in the OC
      group (n = 79), 2.3% (95% CI 1.49, 3.18), was significantly smaller than in the
      control group (p = .03). Over 12 months, the mean percent change in femoral neck
      BMD was -2.2% (95% CI -3.95, -0.39) in the DMPA group, but increased 2.3% (95% CI
      1.29, 3.27) in the control group (p < .001). The increase in mean percent change
      at the femoral neck in the OC group, 0.3% (95% CI -0.87, 1.41), was significantly
      lower than in the control group (p = .03). CONCLUSIONS: Our study contributes to
      an increasing body of knowledge indicating a negative impact of DMPA on bone
      health in young women. Additional findings suggest a potential adverse effect of
      an OC containing 20 microg ethinyl estradiol/100 microg levonorgestrel on bone
      health in adolescents.

PMID- 15581523
TI  - The "Safer Choices" intervention: its impact on the sexual behaviors of different
      subgroups of high school students.
AB  - PURPOSE: To measure the relative impact of a school-based human immunodeficiency
      virus (HIV)-, sexually transmitted disease (STD)-, and pregnancy-prevention
      intervention on sexual risk-taking behaviors of different subgroups of students.
      METHODS: Twenty schools were randomly assigned to receive Safer Choices or a
      standard knowledge-based HIV-education program. Safer Choices was designed to
      reduce unprotected sex by delaying initiation of sex, reducing its frequency, or
      increasing condom use. Its five components included: school organization, an
      intensive curriculum with staff development, peer resources and school
      environment, parent education, and school-community linkages. A total of 3869 9th
      grade students were tracked for 31 months. Results are presented for initiation
      of sex, frequency of unprotected sex, number of unprotected sexual partners,
      condom use, and contraceptive use. These results are presented separately by
      gender, race/ethnicity, prior sexual experience, and prior sexual risk-taking.
      Statistical analyses included multilevel, repeated measures logistic and Poisson
      regression models. RESULTS: Safer Choices had one or more positive behavioral
      effects on all subgroups. On four outcomes that could be affected by condom use,
      it had a greater impact on males than on females. It had greater effects on
      Hispanics, including a delay in sexual activity, than on other racial/ethnic
      groups. Its greatest overall effect was an increase in condom use among students
      who had engaged in unprotected sex before the intervention. CONCLUSIONS: Safer
      Choices reduced one or more measures of sexual risk taking over 31 months among
      all groups of youth, and was especially effective with males, Hispanics, and
      youth who engaged in unprotected sex and thus were at higher risk for HIV, other
      STD infections and pregnancy.

PMID- 15581524
TI  - Adolescent pregnancy intentions and pregnancy outcomes: a longitudinal
      examination.
AB  - PURPOSE: (a) To examine different methods of assessing pregnancy intention; (b)
      to identify psychosocial differences between those who indicate pregnancy
      intentions and those who do not; and (c) to examine the relationship between
      pregnancy intentions and subsequent pregnancy at 6-month follow-up in nonpregnant
      (at baseline), sexually experienced adolescent females. METHODS: Longitudinal
      cohort study of 354 sexually experienced female adolescents attending either a
      STD clinic or HMO adolescent medicine clinic in northern California. Student's t
      tests and regressions examined psychosocial differences between females who
      reported "any" and "no" pregnancy intentions. ANOVAs examined differences among
      different combinations of pregnancy plans/likelihood. Chi-square analyses
      assessed associations between baseline pregnancy intentions and subsequent
      pregnancy. RESULTS: Adolescents' reports of their pregnancy plans and their
      assessments of pregnancy likelihood differed from one another (chi2 = 50.39, df =
      1, p < .001). Pregnancy attitudes and baseline contraceptive use differentiated
      those with inconsistent pregnancy intentions (Not Planning, but Likely) from
      those with clear pregnancy intentions (Planning and Likely, and Not Planning and
      Not Likely) (Pregnancy Attitudes: F [2,338] = 68.96, p < .0001; Contraceptive
      Use: F [2,308] = 14.87, p < .0001). Suspected pregnancies and positive pregnancy
      test results were associated with baseline pregnancy intentions (Suspected: chi2
      = 19.08, df = 2, p < .01; Positive Results: chi2 = 8.84, df = 2, p = .015).
      CONCLUSIONS: To reduce adolescent childbearing we must assess pregnancy
      intentions in multiple ways. Information/education might benefit those female
      adolescents with inconsistent reports of pregnancy intentions.

PMID- 15581525
TI  - Home STI testing: the adolescent female's opinion.
AB  - PURPOSE: To assess sexually active adolescent females' attitudes of home tests
      for sexually transmitted infections. METHODS: This study represents a follow-up
      to a study on adolescent attitudes toward different sampling methods for STI
      testing. In the initial study participants completed a pre-examination health
      survey, provided first void urine (FVU) and self-collected vaginal swab samples
      followed by a pelvic examination with STI screening by endocervical swabs.
      Participants' attitudes about the three collection techniques were assessed at
      the end of the visit. For the current study, this same group of ethnically
      diverse adolescents (13-20-years-old) was contacted by telephone 9 months after
      their initial clinic visit to re-assess their attitudes about the three specimen
      collection techniques and to evaluate their attitudes regarding the use of home
      STI testing. Friedman tests of mean ranks evaluated teens' rankings of STI
      sampling methods and multivariate regression analysis was used to identify
      predictors of home test preference. RESULTS: Home urine testing was the first
      choice for STI screening followed by the FVU, self-obtained vaginal swab and
      endocervical swab collected in a clinical setting. FVU was preferred to self
      collected vaginal swabs (p = .01). Adolescents who worried about having an STI
      were more likely to favor home urine testing (OR 5.5, p = .01). Only 22% would
      seek any STI screening if asymptomatic. CONCLUSIONS: Because young women
      preferred home STI testing, this may be an additional option, as the foundation
      for such testing kits has progressed. Adolescent preferences may be heavily
      influenced by the pelvic examination experience. Because of the largely
      asymptomatic nature of CT infections, multiple screening options (clinical and
      home-based) need to be available to increase access to care.

PMID- 15581526
TI  - Trajectories of depressive symptoms among high risk African-American adolescents.
AB  - PURPOSE: To examine the trajectories of depressive symptoms among African
      American youth and the psychosocial factors associated with these trajectories.
      METHODS: The sample included 579 African-American adolescents who were at risk of
      dropping out of school, interviewed annually starting from ninth grade for 4
      years. The measures included depressive symptoms, anxiety symptoms, self-esteem,
      stress, and active coping; all self-reported. We used cluster analysis to develop
      longitudinal trajectories of depression in our sample. RESULTS: Four different
      trajectories of depressive symptoms were found that represented the changes in
      depressive symptoms among the participants. These trajectories are: consistently
      high (15.9%), consistently low (21.1%), decreasing (41.8%), and increasing
      (21.2%) depressive symptoms. The results from the comparisons of the trajectories
      indicated that adolescents who presented consistently high levels of depressive
      symptoms were more likely to be female, reported more anxiety symptoms, lower
      self-esteem, higher stress, and lower grade point average (GPA) compared with
      adolescent members of the other trajectories. DISCUSSION: Depressive symptoms may
      be manifested in different ways according to the patterns of change. Different
      correlates are associated with these trajectories of depressive symptoms and
      provide insights about the antecedents and consequences of the patterns of change
      in depressive symptoms.

PMID- 15581527
TI  - A predictive model of hopefulness for adolescents.
AB  - PURPOSE: To develop a predictive model of hopefulness using the variables of age,
      gender, and self-esteem among a sample of adolescents with cancer and a sample of
      healthy adolescents. METHODS: Forty-five healthy adolescents were individually
      matched with 45 adolescents with cancer on the basis of gender and age. Of the 90
      subjects included in this study, 48 were male and 42 were female; half of the
      males (n = 24) and half of the females (n = 21) had cancer. Perceived level of
      self-esteem was measured using the Coppersmith Self-Esteem Inventory (SEI), and
      their degree of hopefulness was measured with the Hopefulness Scale for
      Adolescents (HSA). Data were analyzed using the Statistical Analysis System (SAS)
      Version 8. RESULTS: Adolescents' perceived level of self-esteem and hopefulness
      did not differ by gender or disease status. Patients with cancer had a
      significantly higher mean hopefulness score than healthy subjects (p = .031), and
      those adolescents with cancer did not have a lower perceived sense of self-esteem
      than healthy adolescents. The correlation coefficients between SEI and HSA were
      statistically significant for females with cancer, r = 0.723 (p < .001) and for
      healthy females, r = 0.676 (p < .001). In contrast, the correlations between SEI
      and HSA for males were not statistically significant. A model was constructed to
      predict a subject's hopefulness score that included the variables of self-esteem
      (p < .001), gender (p = .001), disease status (p = .005), and the interaction
      between self-esteem and gender (p = .002). CONCLUSIONS: The findings of this
      study demonstrate that hopefulness is a coping strategy used by female
      adolescents, both healthy and ill, that is closely related to their perceived
      sense of self-esteem.

PMID- 15581528
TI  - What influences university students' intentions to practice safe sun exposure
      behaviors?
AB  - PURPOSE: To apply Protection Motivation Theory to examine adolescents' intentions
      to perform safe sun exposure behaviors. METHODS: A total of 239 students (aged 18
      to 22 years) from two British universities were recruited to the study. The
      majority of participants were white (68%), 29% were classified as Asian, and the
      remaining 3% were Afro-Caribbean. Participants completed a questionnaire
      comprising items examining the components of Protection Motivation Theory.
      Intention to perform safe sun exposure behaviors was examined by asking
      participants to indicate their agreement with five statements about future sun
      exposure behaviors. RESULTS: Hierarchical multiple regression analysis revealed
      that the threat appraisal components of Protection Motivation Theory were
      stronger predictors of intention to perform safe sun exposure behaviors
      (accounting for 15% of the variance) than the coping appraisal components
      (accounting for 3% of the variance). However, previous performance of similar
      behaviors emerged as the strongest overall predictor of intention to perform safe
      sun exposure behaviors (beta = -.514, p < .01), followed by perceived
      vulnerability to developing skin cancer (beta = .232, p < .01) and practicing
      skin and naevi self examination behaviors (beta = -.172, p < .01). CONCLUSIONS:
      The results suggest that a strategic sun protection education campaign is
      necessary with the aim of encouraging adaptive sun behaviors by emphasizing the
      risk of skin cancer associated with sunburn.

PMID- 15581529
TI  - Reducing risk, increasing protective factors: findings from the Caribbean Youth
      Health Survey.
AB  - PURPOSE: To identify the prevalence of health-compromising behaviors, and the
      risk and protective factors associated with them among youth in the Caribbean,
      and to predict the likelihood of these outcomes given the presence or absence of
      the risk and protective factors. METHODS: Analyses were done on the results of a
      1997-98 survey of over 15,500 young people in nine countries of the Caribbean
      Community. The four health-compromising behaviors studied included violence
      involvement, sexual intercourse, tobacco use, and alcohol use. Logistic
      regression was used to identify the strongest risk and protective factors, and
      also to create models for predicting the outcomes given combinations of the risk
      and protective factors. RESULTS: Rage was the strongest risk factor for every
      health-compromising behavior for both genders, and across all age groups, and
      school connectedness was the strongest protective factor. For many of the
      outcomes studied, increased protective factors were associated with as much or
      more reduction of involvement in health-compromising behaviors than a decrease in
      risk factors. CONCLUSION: This research suggests the importance of strengthening
      the protective factors in the lives of vulnerable youth not just reducing risk.

PMID- 15581530
TI  - Prevalence and correlates of illicit methylphenidate use among 8th, 10th, and
      12th grade students in the United States, 2001.
AB  - The prevalence and correlates of illicit methylphenidate use were examined within
      a nationally representative U.S. sample of 8th, 10th, and 12th graders. The
      annual prevalence of illicit methylphenidate use was 4%. Race, grade level,
      geographical region, grade point average, and substance use were all
      significantly associated with illicit methylphenidate use.

PMID- 15581531
TI  - Seroprevalence of hepatitis C among a juvenile detention population.
AB  - The seroprevalence and determinants of hepatitis C virus (HCV) infection among
      adolescents in juvenile detention centers in Riverside County was assessed. Among
      728 participants, 16 (2.2%, 95% CI 1.1%, 3.3%) demonstrated serologic evidence of
      HCV infection. Adolescents with a history of injection drug use (adjusted OR =
      10.8, 95% CI 2.6, 45.3, P < .001) were more likely to be HCV seropositive,
      however the frequency of reported injection drug use was just 4%, and only 12% of
      HCV infection could be attributable to injecting drugs in this population.
      Additional information is needed on risk factors for HCV infection in adolescent
      populations. The relatively low level of HCV infection observed in this juvenile
      detention population underscores the opportunity for implementation of targeted
      intervention efforts.

PMID- 15581532
TI  - Adolescent mothers: support needs, resources, and support-education
      interventions.
AB  - Adolescent mothers are prone to live in poor conditions, lack adequate financial
      resources, suffer high stress, encounter family instability, and have limited
      educational opportunities. These factors contribute to inadequate parent-child
      interactions and diminished infant development. Social support can promote
      successful adaptation for adolescent mothers and their children. This review
      article describes the support needs and challenges faced by adolescent parents
      and their children, the support resources available to and accessed by adolescent
      parents, and existing support-education intervention studies, to provide
      directions for future research. Relevant research published between January 1982
      and February 2003 was obtained from online database indices and retrieved article
      bibliographies. Frequently encountered problems included small sample sizes and
      attrition, lack of suitable comparison groups, and measurement inconsistencies.
      When planning support-education interventions, content, duration, intensity,
      mode, level, intervention agents, and targets should be considered. Future
      research can address these challenges.

PMID- 15581533
TI  - Sociodemographic and symptom correlates of fatigue in an adolescent primary care
      sample.
AB  - PURPOSE: To describe the prevalence of prolonged fatigue, chronic fatigue
      syndrome (CFS)-like illness, and associated symptom patterns in adolescents
      attending primary care. METHODS: The design was cross-sectional. A questionnaire
      designed by the authors assessing fatigue and associated symptoms was
      administered to 901 adolescents (aged 11-18 years) attending 12 primary care
      clinics in the Chicago area. Prevalence rates for prolonged fatigue and CFS-like
      illness were calculated. Univariate comparisons involving sociodemographic data
      and fatigue severity were made between adolescents with and without prolonged
      fatigue, and sociodemographic and symptom predictors of prolonged fatigue were
      identified using logistic regression analysis. RESULTS: Prolonged fatigue (> or =
      1 month) occurred at a rate of 8.0% and CFS-like illness occurred at a rate of
      4.4%. Adolescents with prolonged fatigue were significantly older and also
      reported greater fatigue severity than those without fatigue. Findings from
      logistic regression indicated that, in addition to increasing age, headaches,
      muscle pains, fever, and fatigue made worse by exercise were significantly
      associated with prolonged fatigue. CONCLUSIONS: Abnormal fatigue is a disabling
      and prevalent condition in adolescents in primary care. It is associated with a
      number of additional symptoms, many of which may have viral origins.

PMID- 15581534
TI  - Sexual possibility situations and sexual behaviors among young adolescents: the
      moderating role of protective factors.
AB  - PURPOSE: To examine sexual possibility situations (SPS) and protective practices
      associated with involvement in intimate sexual behaviors and the initiation of
      sexual intercourse among young adolescents and to determine if protective factors
      moderate the relationship between SPS and sexual behaviors. METHODS: Data for
      these analyses were obtained from the baseline assessment for adolescents
      conducted as part of an HIV prevention study called "Keepin' it R.E.A.L.!" The
      study was conducted with a community-based organization (CBO) in an urban area
      serving a predominantly African-American population. In addition to items
      assessing SPS, intimate sexual behaviors, and initiation of sexual intercourse,
      adolescents provided information on the following protective factors: educational
      goals, self-concept, future time perspective, orientation to health, self
      efficacy, outcome expectations, parenting, communication, values, and prosocial
      activities. Background personal information, including age and gender, was also
      collected. The analyses were conducted on data from 491 predominantly African
      American adolescents, 61% of whom were boys. Variables were combined to form SPS
      and protective indices that were used in the first set of regression analyses. In
      a second set of analyses, the indices were unbundled and individual variables
      were entered into regression analyses. RESULTS: Both SPS and protective indices
      explained significant portions of variance in intimate sexual behaviors, and the
      SPS index explained a significant portion of variance in the initiation of sexual
      intercourse. The regression analysis using the unbundled SPS and protective
      factors revealed the following statistically significant predictors for intimate
      sexual behaviors: age, gender, time alone with groups of peers, time alone with a
      member of the opposite sex, behavior self-concept, popularity self-concept, self
      efficacy for abstinence, outcome expectations for abstinence, parental control,
      personal values, and parental values. A similar regression analysis revealed that
      age, time alone with a member of the opposite sex, and personal values were
      significant predictors of initiation of sexual intercourse. CONCLUSIONS: These
      results provide evidence for the important role of protective factors in
      explaining early involvement in sexual behaviors and show that protective factors
      extend beyond personal characteristics to include both familial and peer factors.

PMID- 15581535
TI  - Maternal/female caregiver influences on adolescent indoor tanning.
AB  - PURPOSE: To identify aspects of maternal/female caregiver (MFC) influences on
      adolescents' indoor tanning, including modeling, cognitions (MFC knowledge and
      attitudes about indoor tanning), and gatekeeping/monitoring (MFC permissiveness
      and concern) of indoor tanning. METHODS: A telephone survey of adolescents aged
      14-17 years and their female parent/caregiver in Minnesota and Massachusetts was
      conducted in 2000-2001 (n = 1284 matched pairs). Logistic regression was used to
      obtain odds ratios for relationships between measures of MFC influence and teens'
      indoor tanning practices, adjusting for demographic and sun sensitivity
      differences. RESULTS: Separately, each of the five MFC influence variables was
      significantly associated with adolescents' indoor tanning practices. In a
      multivariate model, significant independent contributors were parents' behavior,
      parents' concern about their children's indoor tanning practices, and MFC
      permissiveness of teen indoor tanning. Using a combined summed scale of the 5
      influence factors, there was a monotonically increasing likelihood of tanning
      with each incremental scale increase: (in comparison to none, 1 factor aOR = 4.1,
      95% CI: 1.3, 12.8; any 2 factors aOR = 8.3, 95% CI: 2.8, 24.6; any 3 factors aOR
      = 14.3, 95% CI = 4.9, 41.8; any 4 factors aOR = 30.5, 95% CI: 10.3, 90.3; all 5
      factors aOR = 66.0, 95% CI: 20.0, 217.6). CONCLUSIONS: Mothers/female caregivers
      may be a powerful influence on their teenagers' indoor tanning use, and are an
      important target for future health promotion efforts to discourage youth indoor
      tanning.

PMID- 15581536
TI  - Adolescent alcohol initiation: a review of psychosocial risk factors.
AB  - Longitudinal research studies focused on alcohol use initiation in adolescence
      were reviewed to determine which variables function as antecedent predictors or
      risk factors. Only studies that focused on time-1 abstainers were included.
      Classes of risk factors examined include sociodemographic, family, peer,
      personality, and behavioral variables. The most consistent antecedent risk
      factors for starting to drink in adolescence were parental and peer approval and
      models for drinking and drug use as well as adolescents' own prior involvement in
      delinquent behavior. There was little evidence for gender differences in risk
      factors for alcohol use initiation. Secondary analyses of existing longitudinal
      data sets are encouraged to examine whether there are ethnic/racial differences
      in the risk factors for starting to drink and to establish those factors that
      serve a protective or buffering function, delaying onset of alcohol use in
      adolescence.

PMID- 15581538
TI  - Will new agreement bring globalisation closer?

PMID- 15581537
TI  - What do adolescents want? An exploratory study regarding end-of-life decision
      making.
AB  - PURPOSE: To explore whether differences exist between chronically ill and healthy
      adolescents with regard to their attitudes about end-of-life (EOL) issues.
      METHODS: A convenience sample of 25 adolescents without and 25 with a chronic
      illness, aged 13 to 21 years, were surveyed in hospital clinics, using a 25-item
      instrument; 60% were female and 76% were African-American. Items were developed
      based on previous research, interviews with health care providers, and a focus
      group with patients. Data were analyzed using the Fisher's exact test for 2
      tailed p values. RESULTS: Ninety-six percent of chronically ill and 88% of
      healthy teens want to share decision-making if they are very ill; 76% prefer to
      discuss their wishes earlier in the course of a life-threatening illness. There
      was a trend for chronically ill adolescents to prefer to wait until later in the
      course of their illness (32% at diagnosis, 32% when first ill, 20% first
      hospitalization, or 16% if dying), when compared with their healthy peers (68% at
      diagnosis, 20% first ill, 4% first hospitalization, 8% if dying) (p = .074).
      Chronically ill adolescents were significantly more likely to prefer to wait to
      have these discussions, if the data were collapsed for time (first hospitalized
      and/or dying) (Fisher's p = .037). Half of all adolescents believed that they
      would be allowed to change their minds once they had made a decision. Eighty
      percent of chronically ill and 68% of healthy teens believed that their doctor
      would respect their wishes, while many were uncertain. CONCLUSIONS: Even
      teenagers without chronic illness have thoughts about end-of-life issues and have
      opinions remarkably similar to those of chronically ill teens. Those who are
      chronically ill are less likely to wish to discuss EOL issues early in their
      illness.

PMID- 15581539
TI  - Cure, palliation, and cost in cancer care.

PMID- 15581540
TI  - Italian "Triangle of death".

PMID- 15581541
TI  - B-cell purging in autologous stem-cell transplantation for non-Hodgkin lymphoma.
AB  - Autologous stem-cell transplantation is a common therapy for B-cell non-Hodgkin
      lymphoma. However, a concern with the procedure is the potential of malignant
      cells to reinfuse with the stem-cell graft. Thus attempts have been made to
      purge, or eliminate, malignant cells from the graft. The oldest, and most well
      studied, method for prevention of reinfusion is in vitro use of antibodies
      against B cells that bind or lyse malignant B cells and healthy cells, while
      leaving T cells and stem cells to be reinfused. In the past 5 years,
      investigators have used rituximab, an antibody against CD20, to purge malignant
      cells in vivo without any manipulation in vitro. Both conventional and new
      techniques have shown promise, but their exact role remains to be defined. We
      analysed data on the purging of B cells by use of antibodies in the setting of
      autologous transplantation, with emphasis on the emerging technique of in vivo
      purging.

PMID- 15581542
TI  - Laparoscopic adrenalectomy for malignant disease.
AB  - Malignant tumours of the adrenal gland are uncommon but are associated with
      substantial mortality. For most tumours resection is the only opportunity for
      cure. Advances in diagnostic and surgical techniques have improved the detection
      and treatment of these tumours. Further advances need new ways to make decisions
      about the use of laparoscopic resection for malignant, or potentially malignant,
      adrenal tumours. We review studies on the outcome of laparoscopic adrenalectomy
      for primary adrenal cancer as well as studies on metastatic disease to the
      adrenal glands. There are few prospective data because of the rarity of this
      condition. Careful individual judgment by the surgeon remains the cornerstone of
      safe and complete resection for adrenal malignant disease.

PMID- 15581543
TI  - Late renal metastasis from sigmoid adenocarcinoma.

PMID- 15581544
TI  - Part II: Vaccines for haematological malignant disorders.
AB  - The search for new therapeutic approaches to haematological malignant disease
      involves exploitation of the antitumour potential of adaptive immunity-the most
      specific killing system against cancer currently known. Here, we summarise
      immunological strategies behind active specific immunotherapy, and describe the
      clinical and immunological results from trials published to date. Available data
      in humans support the hypothesis that various vaccination regimens can polarise
      adaptive immunity towards effective control of cancer-cell growth. However, the
      exploratory nature of clinical studies done thus far does not allow any cancer
      vaccine to be used as standard treatment for haematological malignant disorders.
      Because the cause of disease recurrence is the presence of minimal residual
      disease after conventional treatments, the adjuvant setting might be the most
      appropriate therapeutic strategy for active specific immunotherapy, when the
      immunosuppressive effects of bulky disease are virtually absent and when the
      effector-target ratio is favourable. In the near future, completion of randomised
      phase III trials as well as clinical implementation of the most recent insights
      into tumour immunology that aim to overcome immune tolerance towards malignant
      cells should allow investigators to define the actual role of vaccines in the
      management of haematological tumours.

PMID- 15581545
TI  - Is endemic Burkitt's lymphoma an alliance between three infections and a tumour
      promoter?
AB  - Malaria and Epstein-Barr virus (EBV), recognised cofactors for endemic Burkitt's
      lymphoma, are ubiquitous within the lymphoma belt of Africa, and, unless other
      cofactors are involved, the tumour should be much more common than it is. Malaria
      and EBV alone cannot account for the occasional shifting foci and space-time case
      clusters of endemic Burkitt's lymphoma. Arboviruses and plant tumour promoters
      are other possible local cofactors that could explain such characteristics. The
      geographical and age distributions of endemic Burkitt's lymphoma parallel those
      of potentially oncogenic, mosquito-borne arboviruses. Arboviruses seem to be
      associated with case clusters of endemic Burkitt's lymphoma, and symptoms
      compatible with arbovirus infection have been seen immediately before the onset
      of the tumour. RNA and DNA viruses, including EBV, are promoted by extracts of a
      commonly used plant, Euphorbia tirucalli, the distribution of which coincides
      with the boundaries of the lymphoma belt. Extracts of E tirucalli are tumour
      promoters and can induce the characteristic 8;14 translocation of endemic
      Burkitt's lymphoma in EBV-infected cell-lines. They also activate latent EBV in
      infected cells, enhance EBV-mediated cell transformation, and modulate EBV
      specific immunity.

PMID- 15581546
TI  - Aggressive mixed epithelial-stromal tumour of the kidney treated with
      chemotherapy and radiotherapy.

PMID- 15581547
TI  - Dendritic-cell therapy after non-myeloablative stem-cell transplantation for
      renal-cell carcinoma.

PMID- 15581548
TI  - Genomic instability in histologically normal breast tissues: implications for
      carcinogenesis.
AB  - Breast cancer is an important contributor to morbidity and mortality in society,
      but factors that affect the cause of the disease are poorly defined. Genomic
      instability drives tumorigenic processes in invasive carcinomas and premalignant
      breast lesions, and might promote the accumulation of genetic alterations in
      apparently normal tissues before histological abnormalities are detectable.
      Evidence suggests that genomic changes in breast parenchyma affect the behaviour
      of epithelial cells, and ultimately might affect tumour growth and progression.
      Inherent instability in genes that maintain genomic integrity, as well as
      exogenous chemicals and environmental pollutants, have been implicated in breast
      cancer development. Although molecular mechanisms of tumorigenesis are unclear at
      present, carcinogenic agents could contribute to fields of genomic instability
      localised to specific areas of the breast. Understanding the functional
      importance of genomic instability in early carcinogenesis has important
      implications for improvement of diagnostic and treatment strategies.

PMID- 15581549
TI  - Clinical trial design in oncology: protocol design.

PMID- 15581550
TI  - The values of medicine.

PMID- 15581551
TI  - Dispersions of polymer ionomers: I.
AB  - The principal subject discussed in the current paper is the effect of ionic
      functional groups in polymers on the formation of nontraditional polymer
      materials, polymer blends or polymer dispersions. Ionomers are polymers that have
      a small amount of ionic groups distributed along a nonionic hydrocarbon chain.
      Specific interactions between components in a polymer blend can induce
      miscibility of two or more otherwise immiscible polymers. Such interactions
      include hydrogen bonding, ion-dipole interactions, acid-base interactions or
      transition metal complexation. Ion-containing polymers provide a means of
      modifying properties of polymer dispersions by controlling molecular structure
      through the utilization of ionic interactions. Ionomers having a relatively small
      number of ionic groups distributed usually along nonionic organic backbone chains
      can agglomerate into the following structures: (1) multiplets, consisting of a
      small number of tightly packed ion pairs; and (2) ionic clusters, larger
      aggregates than multiplets. Ionomers exhibit unique solid-state properties as a
      result of strong associations among ionic groups attached to the polymer chains.
      An important potential application of ionomers is in the area of thermoplastic
      elastomers, where the associations constitute thermally reversible cross-links.
      The ionic (anionic, cationic or polar) groups are spaced more or less randomly
      along the polymer chain. Because in this type of ionomer an anionic group falls
      along the interior of the chain, it trails two hydrocarbon chain segments, and
      these must be accommodated sterically within any domain structure into which the
      ionic group enters. The primary effects of ionic functionalization of a polymer
      are to increase the glass transition temperature, the melt viscosity and the
      characteristic relaxation times. The polymer microstructure is also affected, and
      it is generally agreed that in most ionomers, microphase-separated, ion-rich
      aggregates form as a result of strong ion-dipole attractions. As a consequence of
      this new phase, additional relaxation processes are often observed in the
      viscoelastic behavior of ionomers. Light functionalization of polymers can
      increase the glass transition temperature and gives rise to two new features in
      viscoelastic behavior: (1) a rubbery plateau above T(g) and (2) a second loss
      process at elevated temperatures. The rubbery plateau was due to the formation of
      a physical network. The major effect of the ionic aggregate was to increase the
      longer time relaxation processes. This in turn increases the melt viscosity and
      is responsible for the network-like behavior of ionomers above the glass
      transition temperature. Ionomers rich in polar groups can fulfill the criteria
      for the self-assembly formation. The reported phenomenon of surface micelle
      formation has been found to be very general for these materials.

PMID- 15581552
TI  - Interpretation of negative values of the interaction parameter in the adsorption
      equation through the effects of surface layer heterogeneity.
AB  - The problem of the negative values of the interaction parameter in the equation
      of Frumkin has been analyzed with respect to the adsorption of nonionic molecules
      on energetically homogeneous surface. For this purpose, the adsorption states of
      a homologue series of ethoxylated nonionic surfactants on air/water interface
      have been determined using four different models and literature data (surface
      tension isotherms). The results obtained with the Frumkin adsorption isotherm
      imply repulsion between the adsorbed species (corresponding to negative values of
      the interaction parameter), while the classical lattice theory for energetically
      homogeneous surface (e.g., water/air) admits attraction alone. It appears that
      this serious contradiction can be overcome by assuming heterogeneity in the
      adsorption layer, that is, effects of partial condensation (formation of
      aggregates) on the surface. Such a phenomenon is suggested in the Fainerman
      Lucassen-Reynders-Miller (FLM) "Aggregation model". Despite the limitations of
      the latter model (e.g., monodispersity of the aggregates), we have been able to
      estimate the sign and the order of magnitude of Frumkin's interaction parameter
      and the range of the aggregation numbers of the surface species.

PMID- 15581553
TI  - The bridging force between two plates by polyelectrolyte chains.
AB  - The interaction between particles in a colloidal system can be significantly
      affected by their bridging by polyelectrolyte chains. In this paper, the bridging
      is investigated by using a self-consistent field approach which takes into
      account the van der Waals interactions between the segments of the
      polyelectrolyte molecules and the plates, as well as the electrostatic and volume
      exclusion interactions. A positive contribution to the force between two plates
      is generated by the van der Waals interactions between the segments and the
      plates. This positive (repulsive) contribution plays an important role in the
      force when the distances between the plates are small. With increasing van der
      Waals interaction strength between segments and plates, the force between the
      plates becomes more repulsive at small distances and more attractive at large
      distances. When the surfaces of the plates have a constant surface electrical
      potential and a charge sign opposite to that of the polyelectrolyte chains, the
      force between the two plates becomes less attractive as the bulk polyelectrolyte
      concentration increases. This behavior is due to a higher bulk counterion
      concentration dissociated from the polyelectrolyte molecules. At short distances,
      the force between plates is more repulsive for stiffer chains. A comparison
      between theoretical and experimental results regarding the contraction of the
      interlayer separation between the platelets of vermiculite clays against the
      concentration of poly(vinyl methyl ether) was made.

PMID- 15581554
TI  - Prediction of three-dimensional fractal dimensions using the two-dimensional
      properties of fractal aggregates.
AB  - Fractal dimension analysis using an optical imaging analysis technique is a
      powerful tool in obtaining morphological information of particulate aggregates
      formed in coagulation processes. However, as image analysis uses two-dimensional
      projected images of the aggregates, it is only applicable to one and two
      dimensional fractal analyses. In this study, three-dimensional fractal dimensions
      are estimated from image analysis by characterizing relationships between three
      dimensional fractal dimensions (D(3)) and one (D(1)) and two-dimensional fractal
      dimensions (D(2) and D(pf)). The characterization of these fractal dimensions
      were achieved by creating populations of aggregates based on the pre-defined
      radius of gyration while varying the number of primary particles in an aggregate
      and three-dimensional fractal dimensions. Approximately 2000 simulated aggregates
      were grouped into 33 populations based on the radius of gyration of each
      aggregate class. Each population included from 15 to 115 aggregates and the
      number of primary particles in an aggregate varied from 10 to 1000.
      Characterization of the fractal dimensions demonstrated that the one-dimensional
      fractal dimensions could not be used to estimate two- and three-dimensional
      fractal dimensions. However, two-dimensional fractal dimensions obtained
      statistically, well-characterized relationships with aggregates of a three
      dimensional fractal characterization. Three-dimensional fractal dimensions
      obtained in this study were compared with previously published experimental
      values where both two-dimensional fractal and three-dimensional fractal data were
      given. In the case of inorganic aggregates, when experimentally obtained three
      dimensional fractal dimensions were 1.75, 1.86, 1.83+/-0.07, 2.24+/-0.22, and
      1.72+/-0.13, computed three-dimensional fractal dimensions using two-dimensional
      fractal dimensions were 1.75, 1.76, 1.77+/-0.04, 2.11+/-0.09, and 1.76+/-0.03,
      respectively. However, when primary particles were biological colloids,
      experimentally obtained three-dimensional fractal dimensions were 1.99+/-0.08 and
      2.14+/-0.04, and computed values were both 1.79+/-0.08. Analysis of the three
      dimensional fractal dimensions with the imaging analysis technique was comparable
      to the conventional methods of both light scattering and electrical sensing when
      primary particles are inorganic colloids.

PMID- 15581555
TI  - Electrokinetics of heterogeneous interfaces.
AB  - The influence of surface heterogeneity of various types on electrokinetic
      parameters is reviewed. The scope of the paper covers classical electrokinetic
      phenomena characterized by linear dependence of electrokinetic parameters vs.
      related driving forces. Neither non-linear effects nor the effects of non
      equilibrium electric double layer are considered. A historical description of
      hydrodynamic aspect of electrokinetic phenomena exploiting the slip plane idea is
      briefly outlined. Attempts to estimate the slip plane location by comparing the
      diffuse layer and zeta potential values for some model systems are presented. The
      surface heterogeneity was divided into three categories. Heterogeneity of the
      first type was related to geometrical morphology of an interfacial region
      characterized by a considerable surface development producing a three-dimensional
      interfacial region. The effects of solid roughness, hairy surface, dense polymer
      layers and gel-like layers are discussed here. The very high surface conductivity
      detected for such interfaces seems to be a good indicator of the presence of
      structured layers of this type. Heterogeneous interfaces of the second class
      cover systems exhibiting non-uniform distribution of surface charge. The non
      uniform surface charge distribution can be either of a molecular (discrete
      charges) or of a microscale (two-dimensional micropatches or three-dimensional
      structures formed by polyelectrolyte multilayers). The last class of systems
      examined includes interfaces composed of charged substrate covered by charged
      bulky objects (particles). In comparison to the homogeneous surfaces, adsorbed
      charged particles modify both hydrodynamic flow and the electrostatic field
      significantly altering the electrokinetic parameters. The new description of
      electrokinetics of composed interfaces presented here takes into account both
      hydrodynamic and electric field modification and is free of the previously
      assumed slip plane shift caused by adsorbed objects. This theoretical approach
      verified by experiments performed on well defined model systems can be
      successfully applied to the interpretation of experimental data obtained for
      surfaces covered by objects difficult to detect.

PMID- 15581556
TI  - High ionic strength electrokinetics.
AB  - The electrokinetic potentials at high ionic strengths can be measured by means of
      electroacoustic method. The reported values are surprisingly high: up to 25 mV in
      1 mol dm(-3) 1:1 electrolyte solution. The IEP of metal oxides in concentrated
      solutions of 1:1 electrolytes shifts to substantially higher pH values with
      respect to the pristine value, although these electrolytes are inert at low
      concentration. The shift in the IEP is salt-specific, and it is correlated with
      the hard-soft character of the anion and of the cation.

PMID- 15581557
TI  - The polarization model for hydration/double layer interactions: the role of the
      electrolyte ions.
AB  - The interactions between hydrophilic surfaces in water cannot be always explained
      on the basis of the traditional Derjaguin-Landau-Verwey-Overbeek (DLVO) theory,
      and an additional repulsion, the "hydration force" is required to accommodate the
      experimental data. While this force is in general associated with the
      organization of water in the vicinity of the surface, different models for the
      hydration were typically required to explain different experiments. In this
      article, it is shown that the polarization-model for the double layer/hydration
      proposed by the authors can explain both (i) the repulsion between neutral lipid
      bilayers, with a short decay length ( approximately 2 A), which is almost
      independent of the electrolyte concentration, and, at the same time, (ii) the
      repulsion between weakly charged mica surfaces, with a longer decay length (
      approximately 10 A), exhibiting not only a dependence on the ionic strength, but
      also strong ion-specific effects. The model, which was previously employed to
      explain the restabilization of protein-covered latex particles at high ionic
      strengths and the existence of a long-range repulsion between the apoferritin
      molecules at moderate ionic strengths, is extended to account for the additional
      interactions between ions and surfaces, not included in the mean field electrical
      potential. The effect of the disorder in the water structure on the dipole
      correlation length is examined and the conditions under which the results of the
      polarization model are qualitatively similar to those obtained by the traditional
      theory via parameter fitting are emphasized. However, there are conditions under
      which the polarization model predicts results that cannot be recovered by the
      traditional theory via parameter fitting.

PMID- 15581558
TI  - Interparticle interactions in concentrate water-oil emulsions.
AB  - The present investigation is based on the description of electrostatic
      interaction in concentrated disperse systems proposed 45 years ago by Albers and
      Overbeek. Starting from their model, we developed a stability theory of
      concentrated Brownian W/O emulsions in which nondeformed droplets undergo
      electrostatic and Van der Waals interactions. While the droplets in dilute
      emulsion may be described by pair interaction, in dense emulsions, every droplet
      is closely surrounded by other droplets, and when two of them come together, not
      only the energy of their pair interaction, but also their interaction with
      surrounding droplets change. Unlike in dilute emulsion, for which the reference
      energy of the pair is the energy at infinity (taken equal to zero), in
      concentrate emulsion, the reference energy is not zero but is the energy of
      interaction with averaged ensemble of nearest droplets. The larger the volume
      fraction, the higher the reference energy and, thus, the lower the energy barrier
      between two coagulating droplets, which enhances the coagulation. In dense
      packing of drops, the energy of interaction and the reference energy coincide,
      therefore, the height of energy barrier vanishes. In contrast with dense
      emulsion, at medium volume fraction, when two coagulating droplets interact only
      with a few nearest neighbors, our analysis shows that the energy barrier may also
      increase, which extends thus the domain of stability. Because in W/O emulsion,
      the thickness of the electric double layer is of the same order or larger than
      the size of droplets, the electrostatic energy was calculated with a correction
      factor beta that accounts for the deviation of double layers from sphericity. A
      more complete van der Waals interaction with account of screening of interaction
      by electrolyte has been used. Both factors promote the decrease of energy barrier
      between coagulating droplets and enhance the coagulation. Our model introduces
      two critical volume fractions. The first one, phi(c1), is the volume fraction
      depending on the characteristics of system (size of drops, thickness of double
      layer, surface potential, dielectric permittivity of medium) that limits the
      validity of the pair interaction model. The second one, phi(c2), is a volume
      fraction that limits the applicability of the simplified model of interaction of
      three or more double layers. By comparing the energies of barrier height and of
      Brownian motion, a critical volume fraction phi(c3) is defined, which determines
      the starting point of rapid coagulation. Finally, the influence of drop
      interaction on gravitational coagulation is also briefly presented. It is shown
      that the probability of coagulation between fixed in space and sedimenting
      droplets is larger than with only Brownian coagulation. Unlike at free
      sedimentation of two identical drops, the gravitation cannot accelerate their
      aggregation. The surface potential, which leads to the equilibration of surface
      forces, gravitational and Archimedes forces for a given volume fraction, is then
      obtained.

PMID- 15581559
TI  - Brownian Dynamics, Molecular Dynamics, and Monte Carlo modeling of colloidal
      systems.
AB  - This paper serves as an introductory review of Brownian Dynamics (BD), Molecular
      Dynamics (MD), and Monte Carlo (MC) modeling techniques. These three simulation
      methods have proven to be exceptional investigative solutions for probing
      discrete molecular, ionic, and colloidal motions at their basic microscopic
      levels. The review offers a general study of the classical theories and
      algorithms that are foundational to Brownian Dynamics, Molecular Dynamics, and
      Monte Carlo simulations. Important topics of interest include fundamental
      theories that govern Brownian motion, the Langevin equation, the Verlet
      algorithm, and the Metropolis method. Brownian Dynamics demonstrates advantages
      over Molecular Dynamics as pertaining to the issue of time-scale separation.
      Monte Carlo methods exhibit strengths in terms of ease of implementation. Hybrid
      techniques that combine these methods and draw from these efficacies are also
      presented. With their rigorous microscopic approach, Brownian Dynamics, Molecular
      Dynamics, and Monte Carlo methods prove to be especially viable modeling methods
      for problems with challenging complexities such as high-level particle
      concentration and multiple particle interactions. These methods hold promising
      potential for effective modeling of transport in colloidal systems.

PMID- 15581561
TI  - The use of isotope effects to determine enzyme mechanisms.
AB  - Isotope effects are one of the most powerful kinetic tools for determining enzyme
      mechanisms. There are three methods of measurement. First, one can compare
      reciprocal plots with labeled and unlabeled substrates. The ratio of the slopes
      is the isotope effect on V/K, and the ratio of the vertical intercepts is the
      isotope effect on V(max). This is the only way to determine V(max) isotope
      effects, but is limited to isotope effects of 5% or greater. The second method is
      internal competition, where the labeled and unlabeled substrates are present at
      the same time and the change in their ratio in residual substrate or in product
      is used to calculate an isotope effect, which is that on V/K of the labeled
      reactant. This is the method used for tritium or (14)C, or with the natural
      abundances of (13)C, (15)N, or (18)O. The third method involves perturbations
      from equilibrium when a labeled substrate and corresponding unlabeled product are
      present at chemical equilibrium. This also gives just an isotope effect on V/K
      for the labeled reactant. The chemistry is typically not fully rate limiting, so
      that the isotope effect on V/K is given by:
      (x)(V/K)=((x)k+c(f)+c(r)(x)K(eq))/(1+c(f)+c(r)) where x defines the isotope (D,
      T, 13, 15, 18 for deuterium, tritium, (13)C, (15)N, or (18)O), and (x)(V/K),
      (x)k, and (x)K(eq) are the observed isotope effect, the intrinsic one on the
      chemical step, and the isotope effect on the equilibrium constant, respectively.
      The constants c(f) and c(r) are commitments in forward and reverse directions,
      and are the ratio of the rate constant for the chemical reaction and the net rate
      constant for release from the enzyme of the varied substrate (direct comparison)
      or labeled substrate (internal competition and equilibrium perturbation) for
      c(f), or the first product released or the one involved in the perturbation for
      c(r). The intrinsic isotope effect, (x)k, can be estimated by comparing deuterium
      and tritium isotope effects on V/K, or by comparing the deuterium isotope effect
      with (13)C ones with deuterated and undeuterated substrates. Adding a secondary
      deuterium isotope effect and its effect on the (13)C one can give an exact
      solution for all intrinsic isotope effects and commitments. The effect of
      deuteration on a (13)C isotope effect allows one to tell if the two isotope
      effects are on the same or different steps. Applications of these methods to
      several enzyme systems will be presented.

PMID- 15581562
TI  - Enzymatic transition states: thermodynamics, dynamics and analogue design.
AB  - Kinetic isotope effects and computational chemistry have defined the transition
      state structures for several members of the N-ribosyltransferase family.
      Transition state analogues designed to mimic their cognate transition state
      structures are among the most powerful enzyme inhibitors. In complexes of N
      ribosyltransferases with their transition state analogues, the dynamic nature of
      the transition state is converted to an ordered, thermodynamic structure closely
      related to the transition state. This phenomenon is documented by peptide bond
      H/D exchange, crystallography and computational chemistry. Complexes with
      substrate, transition state and product analogues reveal reaction coordinate
      motion and catalytic interactions. Isotope-edited spectroscopic analysis and
      binding specificity of these complexes provides information about specific enzyme
      transition state contacts. In combination with protein dynamic QM/MM models, it
      is proposed that the transition state is reached by stochastic dynamic excursions
      of the protein groups near the substrates in the closed conformation. Examples
      from fully dissociated (D(N) *A(N)), hybrid (D(N)A(N)) and symmetric nucleophilic
      displacement (A(N)D(N)) transition states are found in the N-ribosyltransferases.
      The success of transition state analogue inhibitor design based on kinetic
      isotope effects validates this approach to understanding enzymatic transition
      states.

PMID- 15581563
TI  - Quantifying energetic contributions to ground state destabilization.
AB  - Vibrational spectroscopy has identified that in many cases, substrate association
      with enzyme active sites results in significant bond polarization. This bond
      polarization can be attributed to a combination of desolvation, conformational
      restriction, and true polarization by the local electric field. Quantum chemical
      calculations permit the extent of polarization to be quantified both in terms of
      partial charge and energy. The changes in vibrational frequency that occur during
      the binding process necessarily result in equilibrium isotope effects. The
      equilibrium isotope effect on association is one feature that differentiates
      isotope effects on k(cat) and k(cat)/K(m). An improved chemical understanding of
      the changes that occur on substrate binding will help elucidate the role of
      substrate activation in enzyme catalysis.

PMID- 15581564
TI  - Insights into enzyme structure and dynamics elucidated by amide H/D exchange mass
      spectrometry.
AB  - Conformational changes and protein dynamics play an important role in the
      catalytic efficiency of enzymes. Amide H/D exchange mass spectrometry (H/D
      exchange MS) is emerging as an efficient technique to study the local and global
      changes in protein structure and dynamics due to ligand binding, protein
      activation-inactivation by modification, and protein-protein interactions. By
      monitoring the selective exchange of hydrogen for deuterium along a peptide
      backbone, this sensitive technique probes protein motions and structural elements
      that may be relevant to allostery and function. In this report, several
      applications of H/D exchange MS are presented which demonstrate the unique
      capability of amide hydrogen/deuterium exchange mass spectrometry for examining
      dynamic and structural changes associated with enzyme catalysis.

PMID- 15581565
TI  - Detection of novel enzyme intermediates in PEP-utilizing enzymes.
AB  - This review will focus on established and newly emerging strategies for
      identifying and characterizing enzyme intermediates using a rapid transient
      kinetic approach. The merits of this methodology as well as the basics of
      experimental design are described. Several illustrative examples of PEP-utilizing
      enzymes have been chosen as they all perform unique, novel chemistries involving
      enzyme intermediates and have proven to be exciting pharmaceutical targets for
      antibiotics and herbicides. A novel application of this approach using time
      resolved electrospray mass spectrometry to detect chemically labile enzyme
      intermediates is also discussed.

PMID- 15581566
TI  - Divergent evolution in the enolase superfamily: the interplay of mechanism and
      specificity.
AB  - The members of the mechanistically diverse enolase superfamily catalyze different
      overall reactions. Each shares a partial reaction in which an active site base
      abstracts the alpha-proton of the carboxylate substrate to generate an enolate
      anion intermediate that is stabilized by coordination to the essential Mg(2+)
      ion; the intermediates are then directed to different products in the different
      active sites. In this minireview, our current understanding of structure/function
      relationships in the divergent members of the superfamily is reviewed, and the
      use of this knowledge for our future studies is proposed.

PMID- 15581567
TI  - Zinc hydrolases: the mechanisms of zinc-dependent deacetylases.
AB  - A class of metalloenzymes, known as zinc hydrolases, catalyze a variety of
      hydrolytic reactions on many different substrates in important metabolic
      pathways. Deacetylation is an example of one of the types of reactions catalyzed
      by zinc hydrolases. The biological importance of the reactions catalyzed by many
      zinc hydrolases, including zinc-dependent deacetylases, has made these enzymes
      pharmaceutical targets for the development of inhibitors and, therefore, a clear
      understanding of the mechanisms of these enzymes is warranted. This review
      focuses on the current understanding of the mechanisms catalyzed by various zinc
      dependent deacetylases and, in particular, the reaction mechanism catalyzed by
      the enzyme UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase, also
      known as LpxC. In general, the zinc-water functions as the nucleophile with zinc
      stabilization of the tetrahedral intermediate and general-acid-base catalysis
      (GABC) provided by enzyme residue(s). Two types of GABC mechanisms have been
      identified, one that uses a single bifunctional GABC and another that uses a GABC
      pair.

PMID- 15581568
TI  - The serine acetyltransferase reaction: acetyl transfer from an acylpantothenyl
      donor to an alcohol.
AB  - Serine acetyltransferase is a member of the left-handed parallel beta-helix
      family of enzymes that catalyzes the committed step in the de novo synthesis of l
      cysteine in bacteria and plants. The enzyme has an ordered kinetic mechanism with
      acetyl CoA bound prior to l-serine and O-acetyl-l-serine released prior to CoA.
      The rate-limiting step along the reaction pathway is the nucleophilic attack of
      the serine hydroxyl on the thioester of acetyl CoA. Product release contributes
      to rate-limitation at saturating concentrations of reactants. The reaction is
      catalyzed by an active site general base with a pK of 7, which accepts a proton
      from the serine hydroxyl as a tetrahedral intermediate is formed between the
      reactants, and donates it to the thiol of CoA as the intermediate collapses to
      give products. This mechanism is likely the same for all O-acyltransferases that
      catalyze their reaction by direct attack of the alcohol on the acyl donor, using
      an active-site histidine as the general base. Serine acetyltransferase is
      regulated by feedback inhibition by the end product l-cysteine, which acts by
      binding to the serine site in the active site and inducing a conformational
      change that prevents reactant binding. The enzyme also associates with O
      acetylserine sulfhydrylase, the final enzyme in the biosynthetic pathway, which
      contributes to stabilizing the acetyltransferase.

PMID- 15581569
TI  - Structure, function and interfacial allosterism in phospholipase A2: insight from
      the anion-assisted dimer.
AB  - Enzymes that function on membrane surfaces offer many challenges to understanding
      structural and functional details due to the difficulties of obtaining relevant
      information of the protein in a physiological environment. Focusing on this
      aspect of structural biology, it is important to develop conditions that mimic
      the interaction of membrane proteins with their binding surface and ultimately
      the mechanisms of action. This approach has been used to characterize the
      allosteric nature of secreted phospholipase A2 (PLA2) to its substrate interface.
      The breakthrough here was to crystallize the pancreatic group-IB PLA2 in an anion
      assisted dimer with five coplanar phosphate anions bound. In the anion-assisted
      dimer structure one molecule of a tetrahedral mimic inhibitor and five anions are
      shared between the two subunits of the dimer. The sn-2-phosphate of the
      inhibitor, which mimics the tetrahedral intermediate of the esterolysis reaction,
      is bound in the active site of one subunit, and the alkyl chain extends into the
      active site slot of the second subunit across the subunit-subunit interface. This
      interface-bound structural mimic provided insight into the active site
      environment and specific anionic interactions to the i-face of the protein. The
      presence or absence of a single critical active site water, corresponds to the
      difference between the activated or inactivated form of the enzyme. The anion
      assisted dimer structure supports a calcium coordinated nucleophilic water
      mechanism, with its pK(a) modulated by this assisting water. This working model
      has been further strengthened with an enzyme-product complex structure solved
      with the hydrolysis products of the substrate PAF also bound to the anion
      assisted dimer form of PLA2. Additional confirmation of the assisting-water
      mechanism comes from a structure of the inactive zymogen proPLA2 also
      crystallized in an anion-assisted dimer. Remarkably, the assisting water present
      in the activated complex is absent in this proPLA2 structure.

PMID- 15581570
TI  - Molybdenum-containing hydroxylases.
AB  - Unlike monooxygenases, molybdenum-containing hydroxylases catalyze the
      hydroxylation of carbon centers using oxygen derived ultimately from water,
      rather than O(2), as the source of the oxygen atom incorporated into the product,
      and do not require an external source of reducing equivalents. The mechanism by
      which this interesting chemistry takes place has been the subject of
      investigation for some time, and in the last several years the chemical course of
      the reaction has become increasingly well understood. The present minireview
      summarizes recent mechanistic and structure/function studies of members of this
      large and growing family of enzymes.

PMID- 15581571
TI  - 4-Hydroxyphenylpyruvate dioxygenase.
AB  - 4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an Fe(II)-dependent, non-heme
      oxygenase that catalyzes the conversion of 4-hydroxyphenylpyruvate to
      homogentisate. This reaction involves decarboxylation, substituent migration and
      aromatic oxygenation in a single catalytic cycle. HPPD is a member of the alpha
      keto acid dependent oxygenases that typically require an alpha-keto acid (almost
      exclusively alpha-ketoglutarate) and molecular oxygen to either oxygenate or
      oxidize a third molecule. As an exception in this class of enzymes HPPD has only
      two substrates, does not use alpha-ketoglutarate, and incorporates both atoms of
      dioxygen into the aromatic product, homogentisate. The tertiary structure of the
      enzyme would suggest that its mechanism converged with that of other alpha-keto
      acid enzymes from an extradiol dioxygenase progenitor. The transformation
      catalyzed by HPPD has both agricultural and therapeutic significance. HPPD
      catalyzes the second step in the pathway for the catabolism of tyrosine, that is
      common to essentially all aerobic forms of life. In plants this pathway has an
      anabolic branch from homogentisate that forms essential isoprenoid redox
      cofactors such as plastoquinone and tocopherol. Naturally occurring multi-ketone
      molecules act as allelopathic agents by inhibiting HPPD and preventing the
      production of homogentisate and hence required redox cofactors. This has been the
      basis for the development of a range of very effective herbicides that are
      currently used commercially. In humans, deficiencies of specific enzymes of the
      tyrosine catabolism pathway give rise to a number of severe metabolic disorders.
      Interestingly, HPPD inhibitor/herbicide molecules act also as therapeutic agents
      for a number of debilitating and lethal inborn defects in tyrosine catabolism by
      preventing the accumulation of toxic metabolites.

PMID- 15581572
TI  - Structures and mechanisms of Nudix hydrolases.
AB  - Nudix hydrolases catalyze the hydrolysis of nucleoside diphosphates linked to
      other moieties, X, and contain the sequence motif or Nudix box,
      GX(5)EX(7)REUXEEXGU. The mechanisms of Nudix hydrolases are highly diverse in the
      position on the substrate at which nucleophilic substitution occurs, and in the
      number of required divalent cations. While most proceed by associative
      nucleophilic substitutions by water at specific internal phosphorus atoms of a
      diphosphate or polyphosphate chain, members of the GDP-mannose hydrolase sub
      family catalyze dissociative nucleophilic substitutions, by water, at carbon. The
      site of substitution is likely determined by the positions of the general base
      and the entering water. The rate accelerations or catalytic powers of Nudix
      hydrolases range from 10(9)- to 10(12)-fold. The reactions are accelerated 10(3)
      10(5)-fold by general base catalysis by a glutamate residue within, or beyond the
      Nudix box, or by a histidine beyond the Nudix box. Lewis acid catalysis, which
      contributes 10(3)-10(5)-fold to the rate acceleration, is provided by one, two,
      or three divalent cations. One divalent cation is coordinated by two or three
      conserved residues of the Nudix box, the initial glycine and one or two glutamate
      residues, together with a remote glutamate or glutamine ligand from beyond the
      Nudix box. Some Nudix enzymes require one (MutT) or two additional divalent
      cations (Ap(4)AP), to neutralize the charge of the polyphosphate chain, to help
      orient the attacking hydroxide or oxide nucleophile, and/or to facilitate the
      departure of the anionic leaving group. Additional catalysis (10-10(3)-fold) is
      provided by the cationic side chains of lysine and arginine residues and by H
      bond donation by tyrosine residues, to orient the general base, or to promote the
      departure of the leaving group. The overall rate accelerations can be explained
      by both independent and cooperative effects of these catalytic components.

PMID- 15581573
TI  - Redox regulation and reaction mechanism of human cystathionine-beta-synthase: a
      PLP-dependent hemesensor protein.
AB  - Cystathionine beta-synthase in mammals lies at a pivotal crossroad in methionine
      metabolism directing flux toward cysteine synthesis and catabolism. The enzyme
      exhibits a modular organization and complex regulation. It catalyzes the beta
      replacement of the hydroxyl group of serine with the thiolate of homocysteine and
      is unique in being the only known pyridoxal phosphate-dependent enzyme that also
      contains heme b as a cofactor. The heme functions as a sensor and modulates
      enzyme activity in response to redox change and to CO binding. Mutations in this
      enzyme are the single most common cause of hereditary hyperhomocysteinemia.
      Elucidation of the crystal structure of a truncated and highly active form of the
      human enzyme containing the heme- and pyridoxal phosphate binding domains has
      afforded a structural perspective on mechanistic and mutation analysis studies.
      The C-terminal regulatory domain containing two CBS motifs exerts intrasteric
      regulation and binds the allosteric activator, S-adenosylmethionine. Studies with
      mammalian cells in culture as well as with animal models have unraveled multiple
      layers of regulation of cystathionine beta-synthase in response to redox
      perturbations and reveal the important role of this enzyme in glutathione
      dependent redox homestasis. This review discusses the recent advances in our
      understanding of the structure, mechanism, and regulation of cystathionine beta
      synthase from the perspective of its physiological function, focusing on the
      clinically relevant human enzyme.

PMID- 15581574
TI  - Nitroalkane oxidase, a carbanion-forming flavoprotein homologous to acyl-CoA
      dehydrogenase.
AB  - While several flavoproteins will oxidize nitroalkanes in addition to their
      physiological substrates, nitroalkane oxidase (NAO) is the only one which does
      not require the anionic nitroalkane. This, in addition to the induction of NAO by
      nitroethane seen in Fusarium oxysporum, suggests that oxidation of a
      nitroaliphatic species is the physiological role of the enzyme. Mechanistic
      studies of the reaction with nitroethane as substrate have established many of
      the details of the enzymatic reaction. The enzyme is unique in being the only
      flavoprotein to date for which a carbanion is definitively established as an
      intermediate in catalysis. Recent structural analyses show that NAO is homologous
      to the acyl-CoA dehydrogenase and acyl-CoA oxidase families of enzymes. In NAO,
      the glutamate which acts as the active site base in the latter enzymes is
      replaced by an aspartate.

PMID- 15581575
TI  - The enzymology of cystathionine biosynthesis: strategies for the control of
      substrate and reaction specificity.
AB  - The ability of enzymes to catalyze specific reactions, while excluding others, is
      central to cellular metabolism. Control of reaction specificity is of particular
      importance for enzymes that employ catalytically versatile cofactors, of which
      pyridoxal 5'-phosphate is a prime example. Cystathionine gamma-synthase and
      cystathionine beta-synthase are the first enzymes in the transsulfuration and
      reverse transsulfuration pathways, respectively. Each of them occupies branch
      point positions in amino acid metabolism and as such are subject to
      transcriptional and post-translational regulation. Both enzymes catalyze the
      pyridoxal 5'-phosphate-dependent formation of l-cystathionine; however, their
      substrate and reaction specificities are distinct. The mechanisms whereby these
      enzymes control the chemistry of the cofactor are the subject of this review.

PMID- 15581576
TI  - The enzymes of oxalate metabolism: unexpected structures and mechanisms.
AB  - Oxalate degrading enzymes have a number of potential applications, including
      medical diagnosis and treatments for hyperoxaluria and other oxalate-related
      diseases, the production of transgenic plants for human consumption, and
      bioremediation of the environment. This review seeks to provide a brief overview
      of current knowledge regarding the major classes of enzymes and related proteins
      that are employed in plants, fungi, and bacteria to convert oxalate into CO(2)
      and/or formate. Not only do these enzymes employ intriguing chemical strategies
      for cleaving the chemically unreactive C-C bond in oxalate, but they also offer
      the prospect of providing new insights into the molecular processes that underpin
      the evolution of biological catalysts.

PMID- 15581577
TI  - Structure--function studies on the iron-sulfur flavoenzyme glutamate synthase: an
      unexpectedly complex self-regulated enzyme.
AB  - Glutamate synthase (GltS) is, with glutamine synthetase, the key enzyme of
      ammonia assimilation in bacteria, microorganisms and plants. GltS isoforms result
      from the assembly and co-evolution of conserved functional domains. They share a
      common mechanism of reductive glutamine-dependent glutamate synthesis from 2
      oxoglutarate, which takes place within the alpha subunit ( approximately 150 kDa)
      of the NADPH-dependent bacterial enzyme and the corresponding polypeptides of
      other GltS forms, and involves: (i) an Ntn-type amidotransferase domain and (ii)
      a flavin mononucleotide-containing (beta/alpha)(8) barrel synthase domain
      connected by (iii) a approximately 30 A-long intramolecular ammonia tunnel. The
      synthase domain harbors the [3Fe/4S](0,+1) cluster of the enzyme, which
      participates in the electron transfer process from the physiological reductant:
      reduced ferredoxin in the plant-type enzyme or NAD(P)H in the bacterial and the
      non-photosynthetic eukaryotic form. The NAD(P)H-dependent GltS requires a tightly
      bound flavin adenine dinucleotide-dependent reductase (beta subunit,
      approximately 50 kDa), also determining the presence of two low-potential [4Fe
      4S](+1,+2) clusters. Structural, functional and computational data available on
      GltS and related enzymes show how the enzyme may control and coordinate the
      reactions taking place at the glutaminase and synthase sites by sensing substrate
      binding and cofactor redox state.

PMID- 15581578
TI  - Structure and functions of the GNAT superfamily of acetyltransferases.
AB  - The Gcn5-related N-acetyltransferases are an enormous superfamily of enzymes that
      are universally distributed in nature and that use acyl-CoAs to acylate their
      cognate substrates. In this review, we will examine those members of this
      superfamily that have been both structurally and mechanistically characterized.
      These include aminoglycoside N-acetyltransferases, serotonin N-acetyltransferase,
      glucosamine-6-phosphate N-acetyltransferase, the histone acetyltransferases,
      mycothiol synthase, protein N-myristoyltransferase, and the Fem family of amino
      acyl transferases.

PMID- 15581579
TI  - The radical chemistry of galactose oxidase.
AB  - Galactose oxidase is a free radical metalloenzyme containing a novel
      metalloradical complex, comprised of a protein radical coordinated to a copper
      ion in the active site. The unusually stable protein radical is formed from the
      redox-active side chain of a cross-linked tyrosine residue (Tyr-Cys). Biochemical
      studies on galactose oxidase have revealed a new class of oxidation mechanisms
      based on this free radical coupled-copper catalytic motif, defining an emerging
      family of enzymes, the radical-copper oxidases. Isotope kinetics and substrate
      reaction profiling have provided insight into the elementary steps of substrate
      oxidation in these enzymes, complementing structural studies on their active
      site. Galactose oxidase is remarkable in the extent to which free radicals are
      involved in all aspects of the enzyme function: serving as a key feature of the
      active site structure, defining the characteristic reactivity of the complex, and
      directing the biogenesis of the Tyr-Cys cofactor during protein maturation.

PMID- 15581580
TI  - Bacterial defenses against oxidants: mechanistic features of cysteine-based
      peroxidases and their flavoprotein reductases.
AB  - Antioxidant defenses include a group of ubiquitous, non-heme peroxidases,
      designated the peroxiredoxins, which rely on an activated cysteine residue at
      their active site to catalyze the reduction of hydrogen peroxide, organic
      hydroperoxides, and peroxynitrite. In the typical 2-Cys peroxiredoxins, a second
      cysteinyl residue, termed the resolving cysteine, is also involved in
      intersubunit disulfide bond formation during the course of catalysis by these
      enzymes. Many bacteria also express a flavoprotein, AhpF, which acts as a
      dedicated disulfide reductase to recycle the bacterial peroxiredoxin, AhpC,
      during catalysis. Mechanistic and structural studies of these bacterial proteins
      have shed light on the linkage between redox state, oligomeric state, and
      peroxidase activity for the peroxiredoxins, and on the conformational changes
      accompanying catalysis by both proteins. In addition, these studies have
      highlighted the dual roles that the oxidized cysteinyl species, cysteine sulfenic
      acid, can play in eukaryotic peroxiredoxins, acting as a catalytic intermediate
      in the peroxidase activity, and as a redox sensor in regulating hydrogen peroxide
      mediated cell signaling.

PMID- 15581581
TI  - Mechanism of post-translational quinone formation in copper amine oxidases and
      its relationship to the catalytic turnover.
AB  - Copper amine oxidases (CAOs) post-translationally construct a redox-active
      quinone from an amino acid side chain in their polypeptide chain. As such, these
      enzymes illustrate how nature is able to expand upon naturally-occurring side
      chains to create new, catalytically powerful functionalities. The active sites of
      the CAOs are highly unusual in their ability to catalyze two very different
      reactions: single-turnover, oxygen-dependent quinone formation, followed by
      catalytic oxidation (formally dehydrogenation) of amines. This review summarizes
      our current understanding of the pathway whereby the 2,4,5-trihydroxyphenylalanyl
      quinone (TPQ) cofactor is generated from the phenolic side chain of tyrosine.
      This reaction occurs spontaneously intermediates in the presence of O(2) and
      active site bound Cu(II), without the assistance of other proteins or cofactors.
      Ongoing work has focused on uncovering the details of the TPQ formation
      mechanism. A larger goal is to understand how a single active site is capable of
      supporting both quinone formation and subsequent catalytic turnover.

PMID- 15581582
TI  - A twisted base? The role of arginine in enzyme-catalyzed proton abstractions.
AB  - Arginine residues are generally considered poor candidates for the role of
      general bases because they are predominantly protonated at physiological pH.
      Nonetheless, Arg residues have recently emerged as general bases in several
      enzymes: IMP dehydrogenase, pectate/pectin lyases, fumarate reductase, and l
      aspartate oxidase. The experimental evidence suggesting this mechanistic function
      is reviewed. Although these enzymes have several different folds and distinct
      evolutionary origins, a common structural motif is found where the critical Arg
      residue is solvent accessible and adjacent to carboxylate groups. The chemistry
      of the guanidine group suggests unique strategies to lower the pK(a) of Arg.
      Lastly, the presumption that general bases must be predominantly deprotonated is
      revisited.

PMID- 15581583
TI  - Reaction specificity in pyridoxal phosphate enzymes.
AB  - Pyridoxal phosphate enzymes catalyze a wide variety of reaction types on amines
      and amino acids, generally by stabilizing carbanionic intermediates. This makes
      them very useful in cellular metabolism, but it also creates problems in
      controlling the reaction pathway that a given enzyme follows, i.e., in
      controlling reaction specificity. Stereoelectronic effects have been proposed to
      play a major role in determining the bond to Calpha that gets broken in the
      external aldimine intermediate that is common to all PLP enzymes. Here, we
      discuss our work on dialkylglycine decarboxylase aimed at providing direct
      evidence for stereoelectronic control of external aldimine reactivity. Once a
      bond to Calpha has been broken to form the carbanionic intermediate, enzymes must
      also carefully control the fate of this reactive species. Our studies with
      alanine racemase suggest that the enzyme selectively destabilizes the carbanionic
      quinonoid intermediate to promote higher racemization specificity by avoiding
      transamination side reactions.

PMID- 15581584
TI  - Pyruvate formate-lyase activating enzyme: elucidation of a novel mechanism for
      glycyl radical formation.
AB  - Pyruvate formate lyase activating enzyme is a member of a novel superfamily of
      enzymes that utilize S-adenosylmethionine to initiate radical catalysis. This
      enzyme has been isolated with several different iron-sulfur clusters, but single
      turnover monitored by EPR has identified the [4Fe-4S](1+) cluster as the
      catalytically active cluster; this cluster is believed to be oxidized to the [4Fe
      4S](2+) state during turnover. The [4Fe-4S] cluster is coordinated by a three
      cysteine motif common to the radical/S-adenosylmethionine superfamily, suggesting
      the presence of a unique iron in the cluster. The unique iron site has been
      confirmed by Mossbauer and ENDOR spectroscopy experiments, which also provided
      the first evidence for direct coordination of S-adenosylmethionine to an iron
      sulfur cluster, in this case the unique iron of the [4Fe-4S] cluster.
      Coordination to the unique iron anchors the S-adenosylmethionine in the active
      site, and allows for a close association between the sulfonium of S
      adenosylmethionine and the cluster as observed by ENDOR spectroscopy. The
      evidence to date leads to a mechanistic proposal involving inner-sphere electron
      transfer from the cluster to the sulfonium of S-adenosylmethionine, followed by
      or concomitant with C-S bond homolysis to produce a 5'-deoxyadenosyl radical;
      this transient radical abstracts a hydrogen atom from G734 to activate pyruvate
      formate lyase.

PMID- 15581585
TI  - Protein dynamics and electrostatics in the function of p-hydroxybenzoate
      hydroxylase.
AB  - para-Hydroxybenzoate hydroxylase is a flavoprotein monooxygenase that catalyzes a
      reaction in two parts: reduction of the enzyme cofactor, FAD, by NADPH in
      response to binding p-hydroxybenzoate to the enzyme, then oxidation of reduced
      FAD by oxygen to form a hydroperoxide, which oxygenates p-hydroxybenzoate to form
      3,4-dihydroxybenzoate. These diverse reactions all occur within a single
      polypeptide and are achieved through conformational rearrangements of the
      isoalloxazine ring and protein residues within the protein structure. In this
      review, we examine the complex dynamic behavior of the protein that enables
      regulated fast and specific catalysis to occur. Original research papers
      (principally from the past 15 years) provide the information that is used to
      develop a comprehensive overview of the catalytic process. Much of this
      information has come from detailed analysis of many specific mutants of the
      enzyme using rapid reaction technology, biophysical measurements, and high
      resolution structures obtained by X-ray crystallography. We describe how three
      conformations of the enzyme provide a foundation for the catalytic cycle. One
      conformation has a closed active site for the conduct of the oxygen reactions,
      which must occur in the absence of solvent. The second conformation has a partly
      open active site for exchange of substrate and product, and the third
      conformation has a closed protein structure with the isoalloxazine ring rotated
      out to the surface for reaction with NADPH, which binds in a surface cleft. A
      fundamental feature of the enzyme is a H-bond network that connects the phenolic
      group of the substrate in the buried active site to the surface of the protein.
      This network serves to protonate and deprotonate the substrate and product in the
      active site to promote catalysis and regulate the coordination of conformational
      states for efficient catalysis.

PMID- 15581586
TI  - The novel structure and chemistry of iron-sulfur clusters in the
      adenosylmethionine-dependent radical enzyme biotin synthase.
AB  - Biotin synthase is an adenosylmethionine-dependent radical enzyme that catalyzes
      the substitution of sulfur for hydrogen at the saturated C6 and C9 positions in
      dethiobiotin. The structure of the biotin synthase monomer is an (alpha/beta)(8)
      barrel that contains one [4Fe-4S](2+) cluster and one [2Fe-2S](2+) cluster that
      encapsulate the substrates AdoMet and dethiobiotin. The air-sensitive [4Fe
      4S](2+) cluster and the reductant-sensitive [2Fe-2S](2+) cluster have unique
      coordination environments that include close proximity to AdoMet and DTB,
      respectively. The relative positioning of these components, as well as several
      conserved protein residues, suggests at least two potential catalytic mechanisms
      that incorporate sulfur from either the [2Fe-2S](2+) cluster or a cysteine
      persulfide into the biotin thiophane ring. This review summarizes an accumulating
      consensus regarding the physical and spectroscopic properties of each FeS
      cluster, and discusses possible roles for the [4Fe-4S](2+) cluster in radical
      generation and the [2Fe-2S](2+) cluster in sulfur incorporation.

PMID- 15581587
TI  - The roles of the essential Asp-48 and highly conserved His-43 elucidated by the
      pH dependence of the pseudouridine synthase TruB.
AB  - All known pseudouridine synthases have a conserved aspartic acid residue that is
      essential for catalysis, Asp-48 in Escherichia coli TruB. To probe the role of
      this residue, inactive D48C TruB was oxidized to generate the sulfinic acid
      cognate of aspartic acid. The oxidation restored significant but reduced
      catalytic activity, consistent with the proposed roles of Asp-48 as a nucleophile
      and general base. The family of pseudouridine synthases including TruB also has a
      nearly invariant histidine residue, His-43 in the E. coli enzyme. To examine the
      role of this conserved residue, site-directed mutagenesis was used to generate
      H43Q, H43N, H43A, H43G, and H43F TruB. Except for phenylalanine, the
      substitutions seriously impaired the enzyme, but all of the altered TruB retained
      significant activity. To examine the roles of Asp-48 and His-43 more fully, the
      pH dependences of wild-type, oxidized D48C, and H43A TruB were determined. The
      wild-type enzyme displays a typical bell-shaped profile. With oxidized D48C TruB,
      logk(cat) varies linearly with pH, suggesting the participation of specific
      rather than general base catalysis. Substitution of His-43 perturbs the pH
      profile, but it remains bell-shaped. The ascending limb of the pH profile is
      assigned to Asp-48, and the descending limb is tentatively ascribed to an active
      site tyrosine residue, the bound substrate uridine, or the bound product
      pseudouridine.

PMID- 15581588
TI  - Effects of pressure on deuterium isotope effects of yeast alcohol dehydrogenase
      using alternative substrates.
AB  - Hydrostatic pressure causes biphasic effects on the oxidation of alcohols by
      yeast alcohol dehydrogenase as expressed on the kinetic parameter V/K which
      measures substrate capture. Moderate pressure increases capture by activating
      hydride transfer, whose transition-state must therefore have a smaller volume
      than the free alcohol plus the capturing form of enzyme, with DeltaV(double
      dagger)=-30 mL mol(-1) for isopropanol. A comparison of these effects with those
      on the oxidation of deutero-isopropanol generates a monophasic decrease in the
      intrinsic isotope effect; therefore, the volume of activation for the transition
      state of deuteride transfer must be even more negative, by 7.6 mL mol(-1). The
      pressure data extrapolate and factor the kinetic isotope effect into a semi
      classical reactant-state component, with a null value of k(H)/k(D)=1, and a
      transition-state component of Q(H)/Q(D)=4, suggestive of hydrogen tunneling.
      Pressures above 1.5 kbar decrease capture by favoring a minor conformation of
      enzyme which binds nicotinamide adenine dinucleotide (NAD(+)) less tightly. This
      inactive conformation has a smaller volume than active E-NAD(+), with a
      difference of 74 mL mol(-1) and an equilibrium constant of 93 between them, at
      one atmosphere of pressure. These results are virtually identical to those
      obtained with benzyl alcohol and give credence to this method of analysis.
      Moreover, qualitatively similar results with greater pressure sensitivity but
      less precision are obtained using ethanol as a substrate, only with pressure
      driving the value of the isotope effect to a value less than (D)k=1.03 directly,
      without extrapolation. The ethanol data verify the most surprising finding of
      these studies, namely that the entire kinetic isotope effect arises from a
      transition-state phenomenon.

PMID- 15581589
TI  - Proceedings of the 15th International Symposium on Microsomes and Drug
      Oxidations. July 4-9, 2004. Mainz, Germany.

PMID- 15581590
TI  - Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1
      mediated degradation of the protein by proteasome.
AB  - Under homeostatic conditions, Nrf2 activity is constitutively repressed. This
      process is dependent on Keap1, to which Nrf2 binds through the Neh2 domain. Since
      the N-terminal subdomain of Neh2 (Neh2-NT) contains evolutionarily conserved
      motifs, we examined the roles they play in the degradation of Nrf2. In Neh2-NT,
      we defined a novel motif that is distinct from the previously characterized
      DIDLID motif and designated it DLG motif. Deletion of Neh2-NT or mutation of the
      DLG motif largely abolished the Keap1-mediated degradation of Nrf2. These
      mutations were found to enfeeble the binding affinity of Nrf2 to Keap1. The Neh2
      NT subdomain directed DLG-dependent, Keap1-independent, degradation of a reporter
      protein in the nucleus. By contrast, mutation of DLG did not affect the half-life
      of native Nrf2 protein in the nucleus under oxidative stress conditions. These
      results thus demonstrate that DLG motif plays essential roles in the Keap1
      mediated proteasomal degradation of Nrf2 in the cytoplasm.

PMID- 15581591
TI  - Modelling atypical CYP3A4 kinetics: principles and pragmatism.
AB  - The Michaelis-Menten model, and the existence of a single active site for the
      interaction of substrate with drug metabolizing enzyme, adequately describes a
      substantial number of in vitro metabolite kinetic data sets for both clearance
      and inhibition determination. However, in an increasing number of cases
      (involving most notably, but not exclusively, CYP3A4), atypical kinetic features
      are observed, e.g., auto- and heteroactivation; partial, cooperative, and
      substrate inhibition; concentration-dependent effector responses
      (activation/inhibition); limited substrate substitution and inhibitory
      reciprocity necessitating sub-group classification. The phenomena listed above
      cannot be readily interpreted using single active site models and the literature
      indicates that three types of approaches have been adopted. First the 'nai ve'
      approach of using the Michaelis-Menten model regardless of the kinetic behaviour,
      second the 'empirical' approach (e.g., employing the Hill or uncompetitive
      inhibition equations to model homotropic phenomena of sigmoidicity and substrate
      inhibition, respectively) and finally, the 'mechanistic' approach. The later
      includes multisite kinetic models derived using the same rapid equilibrium/steady
      state assumptions as the single-site model. These models indicate that 2 or 3
      binding sites exist for a given CYP3A4 substrate and/or effector. Multisite
      kinetic models share common features, depending on the substrate kinetics and the
      nature of the effector response observed in vitro, which allow a generic model to
      be proposed. Thus although more complex than the other two approaches, they show
      more utility and can be comprehensively applied in relatively simple versions
      that can be readily generated from generic model. Multisite kinetic features,
      observed in isolated hepatocytes as well as in microsomes from hepatic tissue and
      heterologous expression systems, may be evident in substrate depletion-time
      profiles as well as in metabolite formation rates. Failure to adequately account
      for multisite kinetic phenomena will compromise any attempts to predict human
      drug clearance and drug-drug interaction potential from in vitro data.

PMID- 15581592
TI  - Progress in cytochrome P450 active site modeling.
AB  - Models capable of predicting the possible involvement of cytochromes P450 in the
      metabolism of drugs or drug candidates are important tools in drug discovery and
      development. Ideally, functional information would be obtained from crystal
      structures of all the cytochromes P450 of interest. Initially, only crystal
      structures of distantly related bacterial cytochromes P450 were available
      comparative modeling techniques were used to bridge the gap and produce
      structural models of human cytochromes P450, and thereby obtain some useful
      functional information. A significant step forward in the reliability of these
      models came four years ago with the first crystal structure of a mammalian
      cytochrome P450, rabbit CYP2C5, followed by the structures of two human enzymes,
      CYP2C8 and CYP2C9, and a second rabbit enzyme, CYP2B4. The evolution of a CYP2D6
      model, leading to the validation of the model as an in silico tool for predicting
      binding and metabolism, is presented as a case study.

PMID- 15581593
TI  - Principles of covalent binding of reactive metabolites and examples of activation
      of bis-electrophiles by conjugation.
AB  - Mechanisms of toxicity continue to be important in developing rational strategies
      to deal with chemicals present in the environment. Understanding and predicting
      toxicity have also become a critical step in the process of drug development.
      Covalent binding of chemicals to macromolecules is one aspect of toxicity, and
      the principles and outcomes of the process are considered. Two examples of
      chemicals for which several aspects of metabolism and reactions are understood
      are aflatoxin B(1) and polyhalogenated olefins. Ethylene dibromide is a compound
      that is activated to genotoxic half-mustards by conjugation with glutathione or
      the DNA repair protein O(6)-alkylguanine DNA alkyltransferase (AGT). The AGT
      reaction is unusual, in that crosslinking of the protein to DNA increases
      mutagenicity. One of the involved mechanisms is formation of N(7)-guanyl
      crosslinks and depurination to produce G-->T transversions; other reactions
      appear to yield the additional mutagenic events. The phenomenon of thiol
      conjugation to increase mutagenicity is widespread among bis-electrophiles.

PMID- 15581594
TI  - Role of coactivators in transcriptional activation by the aryl hydrocarbon
      receptor.
AB  - The aryl hydrocarbon receptor (AHR) mediates the carcinogenic and other toxic
      effects of a variety of environmental pollutants, including 2,37,8
      tetrachlorodibenzo-p-dioxin (TCDD), and some polycyclic aromatic hydrocarbons
      (PAHs). In most if not all cases, these deleterious effects depend upon
      modulation of gene transcription effected by the ligand-bound AHR. The responsive
      genes required for toxicity of TCDD have yet to be defined. However, induction of
      Cyp1a1 is known to represent a significant event in the toxicity of PAHs.
      Furthermore, the Cyp1a1 gene provides a model system for studying the mechanism
      of gene transcription by AHR. This review discusses the roles of transcriptional
      coactivator proteins in induction of Cyp1a1 by AHR ligands. Coactivators
      physically associate with the gene upon induction, and provide a bridge between
      AHR molecules, located at 5'enhancer elements, and general transcription factors,
      located at the promoter of the gene. Studies on the endogenous Cyp1a1 gene in its
      natural chromosomal setting are emphasized. The recent development of several new
      experimental techniques including the chromatin immunoprecipitation (ChIP) assay,
      RNA interference, and real-time PCR has provided a major boost to such studies.
      Future directions for research are also discussed. Since variations in
      coactivator expression or activity may result in inter-individual differences in
      response to AHR ligands, and may also underlie tissue-specific differences in
      sensitivity to such ligands during development, and in adulthood, the role of
      coactivators in transcriptional activation by AHR constitutes a very important
      area of research.

PMID- 15581595
TI  - Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR,
      and FXR.
AB  - Cloning and characterization of the orphan nuclear receptors constitutive
      androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) led to
      major breakthroughs in studying drug-mediated transcriptional induction of drug
      metabolizing cytochromes P450 (CYPs). More recently, additional roles for CAR and
      PXR have been discovered. As examples, these xenosensors are involved in the
      homeostasis of cholesterol, bile acids, bilirubin, and other endogenous
      hydrophobic molecules in the liver: CAR and PXR thus form an intricate regulatory
      network with other members of the nuclear receptor superfamily, foremost the
      cholesterol-sensing liver X receptor (LXR, NR1H2/3) and the bile-acid-activated
      farnesoid X receptor (FXR, NR1H4). In this review, functional interactions
      between these nuclear receptors as well as the consequences on physiology and
      pathophysiology of the liver are discussed.

PMID- 15581596
TI  - Coordinate transcriptional regulation of bile acid homeostasis and drug
      metabolism.
AB  - Drugs and bile acids are taken up into hepatocytes by specialized transport
      proteins localized at the basolateral membrane, e.g., organic anion transporting
      polypeptides . Following intracellular metabolism by cytochrome P450 (CYP)
      enzymes, drug metabolites are excreted into bile or urine via ATP-dependent
      multidrug resistance proteins (MDR1 and MRPs). Bile acids are excreted mainly via
      the bile salt export pump (BSEP, ABCB11). The genes coding for drug and bile acid
      transporters and CYP enzymes are regulated by a complex network of
      transcriptional cascades, notably by the ligand-activated nuclear receptors FXR,
      PXR, and CAR and by the ligand-independent nuclear receptor HNF-4alpha. The bile
      acid synthesizing enzymes CYP7A1, CYP8B1, and CYP27A1 are subject to negative
      feedback regulation by bile acids, which is partly mediated through the
      transcriptional repressor SHP. The role of transcriptional cofactors, such as SRC
      1 and PGC-1, in mediating the gene-specific effects of individual nuclear
      receptors is becoming increasingly evident.

PMID- 15581597
TI  - Vascular protective effects of cytochrome p450 epoxygenase-derived eicosanoids.
AB  - Cytochrome P450 epoxygenases metabolize arachidonic acid to biologically active
      eicosanoids. Primary epoxidation products are four regioisomers of cis
      epoxyeicosatrienoic acid (EET), 5,6-, 8,9-, 11,12-, and 14,15-EET. One of the
      predominant epoxygenase isoforms involved in EET formation belongs to the CYP2
      gene family. In humans, the P450 epoxygenase, CYP2J2, is expressed in the
      cardiovascular system, namely the endothelium, vascular smooth muscle, and
      cardiomyocyte. CYP2J2 possesses vascular protective effects, which include but
      are not limited to, protection against ischemia-reperfusion injury, suppression
      of reactive oxygen species following hypoxia-reoxygenation, inhibition of the pro
      inflammatory transcription factor, nuclear factor-kappaB (NF-kappaB), attenuation
      of vascular smooth muscle migration, and enhancement of a fibrinolytic pathway.
      Although regioisomers of EET elicit these effects to varying degrees, 11,12-EET
      appears to be the most potent with respect to anti-inflammatory, anti-migratory,
      and pro-fibrinolytic effects. Thus, CYP2J2 and its derived arachidonic acid
      metabolites may play important roles in regulating vascular function under normal
      and pathophysiological conditions.

PMID- 15581598
TI  - Comparison between daidzein and genistein antioxidant activity in primary and
      cancer lymphocytes.
AB  - The main objective of this study was to compare the protective effect of daidzein
      and genistein against induced oxidative damage in Jurkat T-cell line and in
      peripheral blood lymphocytes of healthy subjects. After supplementation of cells
      with isoflavones (from 2.5 to 20micromol/L in Jurkat T-cell and from 0.01 to
      2.5micromol/L in primary lymphocytes, 24h), we determined DNA damage induced by
      hydrogen peroxide using the comet assay and lipid peroxidation evaluating
      malondialdehyde (MDA) production after ferrous ion treatment. Supplementation of
      Jurkat cells and primary lymphocytes with both isoflavones significantly
      increased DNA protection from oxidative damage at concentrations between 0.1 and
      5micromol/L (P<0.05), and with just daidzein, at concentrations higher than
      2.5micromol/L, there was a decrease in the production of MDA (P<0.05). Our
      results seem to support that daidzein is just as effective as genistein in
      protecting cells against oxidative damage especially with respect to DNA.
      Moreover, since the protective effect was found at concentrations reachable in
      plasma after soy consumption (less than 2micromol/L), it can be assumed that the
      antioxidant activity of isoflavones could really contribute to the healthy
      properties of soy.

PMID- 15581599
TI  - Metabolic O-demethylation does not alter the influence of isoflavones on the
      biophysical properties of membranes and MRP1-like protein transport activity.
AB  - Multidrug resistance transporter MRP1 could be effectively inhibited by some
      flavonoids. The influence of the two pairs of isoflavones: formononetin/daidzein
      and biochanin A/genistein on the efflux of fluorescent substrate of MRP1-like
      protein from erythrocytes and biophysical properties of lipid membranes has been
      compared. Compounds in each pair differ by the substituent in position 4' of B
      ring of isoflavone molecule. In the process of O-demethylation, CH(3) group
      (present in formonetin and biochanin A) is replaced by hydrogen (daidzein,
      genistein). Inhibition of MRP1-like protein transport activity by methylated and
      demethylated isoflavones was very similar. Their influence on lipid thermotropic
      properties and fluidity of lipid bilayer was not also significantly different.

PMID- 15581600
TI  - Role of mitochondrial cardiolipin peroxidation in apoptotic photokilling of 5
      aminolevulinate-treated tumor cells.
AB  - In 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), ALA taken up by
      tumor cells is metabolized to protoporphyrin IX (PpIX), which sensitizes
      photodamage leading to apoptotic or necrotic cell death. Since lipophilic PpIX
      originates in mitochondria, we postulated that photoperoxidation of highly
      unsaturated cardiolipin (CL), which anchors cytochrome c (cyt c) to the inner
      membrane, is an early proapoptotic event. As initial evidence, PpIX-sensitized
      photooxidation of liposomal CL to hydroperoxide (CLOOH) species precluded cyt c
      binding, but this could be reinstated by GSH/selenoperoxidase (GPX4) treatment.
      Further support derived from site-specific effects observed using (i) a
      mitochondrial GPX4-overexpressing clone (7G4) of COH-BR1 tumor cells, and (ii) an
      ALA treatment protocol in which most cellular PpIX is either inside (Pr-1) or
      outside (Pr-2) mitochondria. Sensitized cells were exposed to a lethal light
      dose, and then analyzed for death mechanism and lipid hydroperoxide (LOOH)
      levels. Irradiated Pr-1 vector control (VC) cells died apoptotically following
      cyt c release and caspase-3 activation, whereas 7G4 cells were highly resistant.
      Irradiated Pr-2 VC and 7G4 cells showed negligible cyt c release or caspase-3
      activation, and both types died via necrosis. CLOOH (detected long before cyt c
      release) accumulated approximately 70% slower in Pr-1 7G4 cells than in Pr-1 VC,
      and this slowdown exceeded that of all other LOOHs. These and related findings
      support the hypothesis that CL is a key upstream target in mitochondria-dependent
      ALA-PDT-induced apoptosis.

PMID- 15581601
TI  - Key NAD+-binding residues in human 15-hydroxyprostaglandin dehydrogenase.
AB  - NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a member of the
      short-chain dehydrogenase/reductase (SDR) family, catalyzes the first step in the
      catabolic pathways of prostaglandins and lipoxins, and is believed to be the key
      enzyme responsible for the biological inactivation of these biologically potent
      eicosanoids. The enzyme utilizes NAD(+) specifically as a coenzyme. Potential
      amino acid residues involved in binding NAD(+) and facilitating enzyme catalysis
      have been partially identified. In this report, we propose that three more
      residues in 15-PGDH, Ile-17, Asn-91, and Val-186, are also involved in the
      interaction with NAD(+). Site-directed mutagenesis was used to examine their
      roles in binding NAD(+). Several mutants (I17A, I17V, I17L, I17E, I17K, N91A,
      N91D, N91K, V186A, V186I, V186D, and V186K) were prepared, expressed as
      glutathione S-transferase (GST) fusion enzymes in Escherichia coli, and purified
      by GSH-agarose affinity chromatography. Mutants I17E, I17K, N91L, N91K, and V186D
      were found to be inactive. Mutants N91A, N91D, V186A, and V186K exhibited
      comparable activities to the wild type enzyme. However, mutants I17A, I17V, I17L,
      and V186I had higher activity than the wild type. Especially, the activities of
      I17L and V186I were increased nearly 4- and 5-fold, respectively. The k(cat)/K(m)
      ratios of all active mutants for PGE(2) were similar to that of the wild type
      enzyme. However, the k(cat)/K(m) ratios of mutants I17A and N91A for NAD(+) were
      decreased 5- and 10-fold, respectively, whereas the k(cat)/K(m) ratios of mutants
      I17V, N91D, V186I, and V186K for NAD(+) were comparable to that of the wild type
      enzyme. The k(cat)/K(m) ratios of mutants I17L and V186A for NAD(+) were
      increased over nearly 2-fold. These results suggest that Ile-17, Asn-91, and Val
      186 are involved in the interaction with NAD(+) and contribute to the full
      catalytic activity of 15-PGDH.

PMID- 15581602
TI  - Relevance of Frank's solvent classification as typically aqueous and typically
      non-aqueous to activities of firefly luciferase, alcohol dehydrogenase, and alpha
      chymotrypsin in aqueous binaries.
AB  - Effects of cosolvent concentration on activity of fire fly luciferase, alpha
      chymotrypsin, and alcohol dehydrogenase from baker's yeast (Saccharomyces
      cerevisiae) have been studied for several solvents with varying hydrophobicities
      (logP from +1.0 to -1.65) and polarities (dielectric constant from 7.4 to 109).
      The inhibitory effect of the cosolvent is examined in light of Frank's
      classification of solvents into 'typically aqueous (TA)' and 'typically non
      aqueous (TNA).' The solvent concentration at which the enzyme activity decreases
      to half, the C(50) values, for TA solvents such as 1-cyclohexyl-2-pyrrolidinone,
      2-butoxyethanol, 1-methyl-2-pyrrolidinone, tetrahydrofuran, t-butanol, and
      ethanol correlate quite well with their critical hydrophobic interaction
      concentration, rather than logP, while those for TNA solvents such as
      acetonitrile, dimethyl formamide, formamide, and dimethyl sulfoxide correlate
      well with logP. The interactions of TA solvents with proteins appear to be
      governed mainly by hydrophobic interactions while both hydrophobic and
      hydrophilic interactions play important role in case of TNA solvents.

PMID- 15581603
TI  - 1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through
      indirect gene activation and receptor stabilization.
AB  - Expression of the vitamin D receptor (VDR) in the kidney and intestine plays a
      major role in calcium homeostasis and the metabolism of 1,25-dihydroxyvitamin
      D(3) (1,25(OH)(2)D(3)). Calcium and 1,25(OH)(2)D(3)-mediated regulation of renal
      and duodenal VDR expression has been analyzed in vivo and the mechanisms
      responsible for the renal regulation have been studied in mouse kidney TCMK-1
      cells. Vitamin D-deficient mice were maintained on diets containing either 0.02
      or 0.47% calcium, with or without 50ng of 1,25(OH)(2)D(3) per day. Renal VDR
      levels were significantly higher in the vitamin D-deficient mice fed the 0.47%
      calcium diet vs. the calcium-restricted diet, and were increased 5-fold by
      1,25(OH)(2)D(3) when dietary calcium was present. The renal VDR transcript was
      expressed at a basal level in the absence of calcium or 1,25(OH)(2)D(3); 50ng of
      1,25(OH)(2)D(3) elevated renal VDR mRNA levels approximately 10-fold in the
      presence of calcium. Neither calcium nor 1,25(OH)(2)D(3) had any significant
      effect on duodenal VDR or VDR mRNA expression. In TCMK-1 cells, 1,25(OH)(2)D(3)
      increased receptor and VDR mRNA content in both low and adequate calcium medium.
      The 1,25(OH)(2)D(3)-mediated increase in VDR mRNA did not result from increased
      stability of the transcript. Further, the increase in mRNA was blocked by
      cycloheximide, indicating a requirement for protein synthesis and an indirect
      regulation of VDR transcription. Thus, both dietary serum calcium and 1,25
      (OH)(2)D(3) are required for VDR expression in kidney but not in intestine where
      neither is required. The 1,25-(OH)(2)D(3) requirement can also be shown in TCMK-1
      cells in vitro, while the calcium requirement was not found.

PMID- 15581604
TI  - Supernatant protein factor stimulates HMG-CoA reductase in cell culture and in
      vitro.
AB  - Supernatant protein factor (SPF) is a 46-kDa cytosolic protein that stimulates
      squalene monooxygenase in vitro and, unexpectedly, cholesterol synthesis in cell
      culture. Because squalene monooxygenase is not thought to be rate-limiting with
      regard to cholesterol synthesis, we investigated the possibility that SPF might
      stimulate other enzymes in the cholesterol biosynthetic pathway. Substitution of
      [(14)C]mevalonate for [(14)C]acetate in McARH7777 hepatoma cells expressing SPF
      reduced the 1.8-fold increase in cholesterol synthesis by half, suggesting that
      SPF acted on or prior to mevalonate synthesis. This conclusion was supported by
      the finding that substitution with [(14)C]mevalonate completely blocked an SPF
      induced increase in squalene synthesis. Evaluation of 2,3-oxidosqualene synthesis
      from [(14)C]mevalonate demonstrated that SPF also stimulated squalene
      monooxygenase (1.3-fold) in hepatoma cells. Immunoblot analysis showed that SPF
      did not increase HMG-CoA reductase or squalene monooxygenase enzyme levels,
      indicating a direct effect on enzyme activity. Addition of purified recombinant
      SPF to rat liver microsomes stimulated HMG-CoA reductase by about 1.5-fold, and
      the SPF-concentration/activation curve paralleled that for the SPF-mediated
      stimulation of squalene monooxygenase. These results reveal that SPF directly
      stimulates HMG-CoA reductase, the rate-limiting step of the cholesterol
      biosynthetic pathway, as well as squalene monooxygenase, and suggest a new means
      by which cholesterol synthesis can be rapidly modulated in response to hormonal
      and environmental signals.

PMID- 15581605
TI  - Epigenetic regulation of the binding activity of translation inhibitory proteins
      that bind the 3' untranslated region of beta-F1-ATPase mRNA by adenine
      nucleotides and the redox state.
AB  - Here, we describe the binding affinities and the regulation of the binding
      activities of the fetal liver proteins that interact with the 3' untranslated
      region of beta-F1-ATPase mRNA (beta-mRNA). These proteins (3'beta FBPs), which
      are involved in the repression of beta-mRNA translation during fetal development,
      have poly(A)-binding activity. Reducing agents do not affect the RNA-binding
      activity of 3'beta FBPs. In contrast, oxidizing and alkylating reagents abolished
      the binding activity of 3'beta FBPs to its target RNA element, an effect that is
      partially prevented by the presence of reducing agents. Interestingly, the
      availability of adenine nucleotides regulates in a concentration-dependent manner
      the binding activities of 3'beta FBPs. The results suggest that epigenetic
      changes that occur at the time of birth affecting both the redox and energy state
      of the liver play a relevant role in the regulation of the binding activities of
      3'beta FBPs and therefore in the translation of beta-mRNA.

PMID- 15581606
TI  - The double life of HOXB4.
AB  - HOXB4 is a homeodomain-containing transcription factor with diverse roles in
      embryonic development and the regulation of adult stem cells. Intriguingly, this
      gene can act in opposite ways when expressed by different cells, promoting the
      proliferation of stem cells whilst activating the apoptotic pathway in some
      embryonic structures. This review considers the basis for these differences in
      terms of the molecular biology of HOXB4 and the cells that express it.

PMID- 15581607
TI  - A model of a transmembrane drug-efflux pump from Gram-negative bacteria.
AB  - In Gram-negative bacteria, drug resistance is due in part to the activity of
      transmembrane efflux-pumps, which are composed of three types of proteins. A
      representative pump from Escherichia coli is an assembly of the trimeric outer
      membrane protein TolC, which is an allosteric channel, the trimeric inner
      membrane proton-antiporter AcrB, and the periplasmic protein, AcrA. The pump
      displaces drugs vectorially from the bacterium using proton electrochemical
      force. Crystal structures are available for TolC and AcrB from E. coli, and for
      the AcrA homologue MexA from Pseudomonas aeruginosa. Based on homology modelling
      and molecular docking, we show how AcrA, AcrB and TolC might assemble to form a
      tripartite pump, and how allostery may occur during transport.

PMID- 15581608
TI  - Molecular signature associated with plasticity of bone marrow cell under
      persistent liver damage by self-organizing-map-based gene expression.
AB  - The mechanism that regulates the plasticity of bone marrow cells (BMCs) into
      hepatocytes is poorly understood. We developed a green fluorescent protein/carbon
      tetrachloride model to find that BMC transplantation recovered liver damage.
      Serum albumin level and liver fibrosis were recovered by BMC transplantation. To
      understand the mechanism, we used DNA-chip technology to profile the change of
      transient gene expression before and after BMC transplantation. On the basis of
      gene expression with self-organizing map using specific equation, genes were
      classified into 153 clusters. The information is useful to understand the
      dramatic gene activation during the process of the plasticity of BMC.

PMID- 15581609
TI  - FIGC, a novel FGF-induced ubiquitin-protein ligase in gastric cancers.
AB  - We have previously shown that fibroblast growth factor receptor 2 (FGFR2) plays
      an important role in gastric carcinogenesis. In this study, we have used a
      differential display approach to identify basic fibroblast growth factor (bFGF)
      inducible genes in gastric cancer cells. Here, we report that one of these genes
      is predicted to encode a RING finger protein, designated FIGC. The FIGC gene was
      found to encode a polypeptide of 381 amino acids with a novel RING finger module
      at the NH2-terminus and the COOH-terminal proline-rich region. Using an in vitro
      ubiquitination assay with recombinant protein, we demonstrate that FIGC has
      intrinsic E3 ubiquitin ligase activity and promotes ubiquitination. Our data
      indicate that FIGC upregulation in response to bFGF in gastric cancer might be
      implicated in carcinogenesis through dysregulation of growth modulator.

PMID- 15581610
TI  - Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria.
AB  - Transgenic Escherichia coli expressing pyrroloquinoline-quinone (PQQ) synthase
      gene from Deinococcus radiodurans showed superior survival during Rose Bengal
      induced oxidative stress. Such cells showed significantly low levels of protein
      carbonylation as compared to non-transgenic control. In vitro, PQQ reacted with
      reactive oxygen species with rate constants comparable to other well known
      antioxidants, producing non-reactive molecular products. PQQ also protected
      plasmid DNA and proteins from the oxidative damage caused by gamma-irradiation in
      solution. The data suggest that radioprotective/oxidative stress protective
      ability of PQQ in bacteria may be consequent to scavenging of reactive oxygen
      species per se and induction of other free radical scavenging mechanism.

PMID- 15581611
TI  - Suppression of human Mnk1 by small interfering RNA increases the eukaryotic
      initiation factor 4F activity in HEK293T cells.
AB  - Short-interfering RNAs (siRNAs) have proved to be a useful tool in studying gene
      function in plants, invertebrates and mammalian systems. Herein, we report the
      use of siRNAs for targeting the human MAP kinase-interacting kinase Mnk1 gene.
      This study demonstrates the efficacy of the designed siRNA in silencing Mnk1 in
      the human cell line HEK293T and shows that Mnk1 suppression decreases eukaryotic
      initiation factor 4E phosphorylation without causing any change in global protein
      synthesis rate and cell proliferation. Interestingly, suppression of Mnk1 results
      in a significant increase in eukaryotic initiation factor 4F complex formation
      after 72 h of transfection.

PMID- 15581612
TI  - A new NF-kappaB inhibitor attenuates a TH1 type immune response in a murine
      model.
AB  - Nuclear factor kappa B (NF-kappaB) plays a wide variety of pathophysiological
      roles and modulation of its pathway can be a good novel drug target. Here, we
      found that our recently synthesized NF-kappaB inhibitor attenuated an ovalbumin
      specific delayed-type hypersensitivity response in vivo and suppressed production
      of IL-12 by dendritic cells and TH1 cytokines by T cells in vitro. These findings
      suggest that the activation of NF-kappaB mounts TH1 type immune responses, and
      that this new NF-kappaB inhibitor has a therapeutic potential in this context.

PMID- 15581613
TI  - Impact of pH on Bax alpha conformation, oligomerisation and mitochondrial
      integration.
AB  - The change in the conformation of Bax at the onset of apoptosis is a determinant
      for the execution of this cell death programme. However, very few models can
      account for this modification and the factors involved in this process remain
      elusive. We have analysed the modifications in the conformation induced by a
      variation in pH using a cell-free assay. We show that a moderate basic or acidic
      pH can induce apoptotic-like changes in the conformation of Bax, such as the
      exposure of the N-terminal or the BH3 domain. These changes in the conformation
      are associated with the binding of Bax to mitochondria and an enhanced Bax homo-
      and oligomerisation. Our results suggest that variations in the pH, in a range
      consistent with that often observed during apoptosis, are sufficient to trigger
      Bax translocation to mitochondria and the subsequent release of apoptogenic
      factors from this organelle.

PMID- 15581614
TI  - NMDA receptor-mediated calcium influx plays an essential role in myoblast fusion.
AB  - Ca2+ influx is known to be prerequisite for myoblast fusion during skeletal
      muscle differentiation. Here, we show that the N-methyl-D-aspartate (NMDA)
      receptor is involved in the Ca2+ influx of C2C12 myoblasts. NMDA receptor (NR) 1
      and NR2D were expressed in the myoblasts during muscle differentiation. Using
      Ca2+ imaging analysis, Ca2+ influx through NRs was directly measured at a single
      cell level. l-Glutamate increased myoblast fusion as well as intracellular Ca2+
      levels, and both effects were completely blocked by MK801, a selective antagonist
      of NRs. Furthermore, treatment with the Ca2+ ionophore A23187 recovered MK801
      mediated inhibition of myoblast fusion. These results suggest that the NRs may
      play an important role in myoblast fusion by mediating Ca2+ influx.

PMID- 15581615
TI  - Biological validation of coenzyme Q redox state by HPLC-EC measurement:
      relationship between coenzyme Q redox state and coenzyme Q content in rat
      tissues.
AB  - The properties of coenzymes Q (CoQ9 and CoQ10) are closely linked to their redox
      state (CoQox/total CoQ) x 100. In this work, CoQ redox state was biologically
      validated by high performance liquid chromatography-electrochemical measurement
      after modulation of mitochondrial electron flow of cultured cells by molecules
      increasing (rotenone, carbonyl cyanide chlorophenylhydrazone) or decreasing
      (antimycin) CoQ oxidation. The tissue specificity of CoQ redox state and content
      were investigated in control and hypoxic rats. In control rats, there was a
      strong negative linear regression between tissular CoQ redox state and CoQ
      content. Hypoxia increased CoQ9 redox state and decreased CoQ9 content in a
      negative linear relationship in the different tissues, except the heart and lung.
      This result demonstrates that, under conditions of mitochondrial impairment, CoQ
      redox control is tissue-specific.

PMID- 15581616
TI  - The Ppz protein phosphatases regulate Trk-independent potassium influx in yeast.
AB  - The Ppz protein phosphatases have been recently shown to negatively regulate the
      major potassium transport system in the yeast Saccharomyces cerevisiae, encoded
      by the TRK1 and TRK2 genes. We have found that, in the absence of the Trk system,
      Ppz mutants require abnormally high concentrations of potassium to proliferate.
      This can be explained by the observation that trk1 trk2 ppz1 or trk1 trk2 ppz1
      ppz2 strains display a very poor rubidium uptake, with markedly increased Km
      values. These cells are very sensitive to the presence of several toxic cations
      in the medium, such as hygromicyn B or spermine, but not to lithium or sodium
      cations. At limiting potassium concentrations, addition of EGTA to the medium
      improves growth of these mutants. Therefore, our results indicate that, in
      addition to their role in regulating Trk potassium transporters, Ppz phosphatases
      (essentially Ppz1), positively affect the residual low affinity potassium
      transport mechanisms in yeast. These findings may provide a new way to elucidate
      the molecular nature of the low affinity potassium uptake system in yeast as well
      as a useful model to analyze the function of plant or mammalian potassium
      channels through heterologous expression in yeast.

PMID- 15581617
TI  - Hepatocyte nuclear factors 1alpha and 4alpha control expression of proline
      oxidase in adult liver.
AB  - Adult liver functions are regulated by several hepatocyte nuclear factors (HNFs).
      HNF4alpha and HNF1alpha are involved in metabolic functions in the liver. The
      expression of proline oxidase (PO) and proline dehydrogenase was downregulated in
      the HNF4alpha liver-specific null mice. In addition, the expression of PO was
      also diminished in the liver derived from HNF1alpha-null mice. The -160 bp
      proximal promoter region of the PO gene has two HNF4alpha- and HNF1alpha-binding
      consensus sites. Transactivation, electrophoretic mobility shift and chromatin
      immunoprecipitation studies revealed that these regions are important for PO
      promoter activity. These results suggested that HNF4alpha and HNF1alpha regulate
      proline metabolism in adult liver.

PMID- 15581618
TI  - The DNA methylation events in normal and cloned rabbit embryos.
AB  - To study the DNA methylation events in normal and cloned rabbit embryos, we
      investigated the methylation status of a satellite sequence and the promoter
      region of a single-copy gene using bisulfite-sequencing technology. During normal
      rabbit embryo development, both sequences maintained hypermethylation status
      until the 8- to 16-cell stage when progressive demethylation took place. In
      cloned embryos, the single-copy gene promoter sequence was rapidly demethylated
      and precociously de novo methylated, while the satellite sequence maintained the
      donor-type methylation status in all examined stages. Our results indicate that
      unique sequences as well as satellite sequences may have aberrant methylation
      patterns in cloned embryos.

PMID- 15581619
TI  - Uncoupling of GPCR and RhoA-induced Ca2+-sensitization of chicken amnion smooth
      muscle lacking CPI-17.
AB  - Ca2+-sensitization of smooth muscle occurs through inhibition of myosin light
      chain phosphatase (MLCP) leading to an increase in the MLCK:MLCP activity ratio.
      MLCP is inhibited through phosphorylation of its regulatory subunit (MYPT-1)
      following activation of the RhoA/Rho kinase (ROK) pathway or through
      phosphorylation of the PP1c inhibitory protein, CPI-17, by PKC delta or ROK.
      Here, we explore the crosstalk between these two modes of MLCP inhibition in a
      smooth muscle of a natural CPI-17 knockout, chicken amnion. GTPgammaS elicited
      Ca2+-sensitized force which was relaxed by GDI or Y-27632, however, U46619,
      carbachol and phorbol ester failed to induce Ca2+-sensitized force, but were
      rescued by recombinant CPI-17, and were sensitive to Y-27632 inhibition. In the
      presence, but not absence, of CPI-17, U46619 also significantly increased
      GTP.RhoA. There was no affect on MYPT-1 phosphorylation at T695, however, T850
      phosphorylation increased in response to GTPgammaS stimulation. Together, these
      data suggest a role for CPI-17 upstream of RhoA activation possibly through
      activation of another PP1 family member targeted by CPI-17.

PMID- 15581620
TI  - Glutamate-evoked redox state alterations are involved in tissue transglutaminase
      upregulation in primary astrocyte cultures.
AB  - The aim of this study was to evaluate the involvement of oxidative stress in
      glutamate-evoked transglutaminase (TGase) upregulation in astrocyte cultures (14
      DIV). A 24 h exposure to glutamate caused a dose-dependent depletion of
      glutathione intracellular content and increased the ROS production in cell
      cultures. These effects were receptor-mediated, as demonstrated by inhibition
      with GYKI 52466. The pre-incubation with glutathione ethyl ester or cysteamine
      recovered oxidative status and was effective in significantly reducing glutamate
      increased tissue TGase. These data suggest that tissue TGase upregulation may be
      part of a biochemical response to oxidative stress induced by a prolonged
      exposure of astrocyte cultures to glutamate.

PMID- 15581621
TI  - Depolarisation of the plasma membrane in the arsenic trioxide (As2O3)-and anti
      CD95-induced apoptosis in myeloid cells.
AB  - Depolarisation of the plasma membrane has been shown to be actively regulated
      during lymphocyte-apoptosis. Here, we present data about anti-Fas and As2O3
      induced depolarisation of myeloid U-937 cells. Anti-Fas but not As2O3-induced
      depolarisation was significantly dependent on caspase-activation. Na+-fluxes
      contributed to the depolarisation in early stages of As2O3-induced apoptosis,
      whereas the membrane potential in late stages depended on Cl- -fluxes. Cl- 
      channels also played an important role in the induction of cell shrinkage in
      As2O3-induced apoptosis. However, none of these ions contributed significantly to
      anti-Fas induced depolarisation. This indicates the existence of different
      mechanisms for apoptotic plasma membrane depolarisation within one cell type.

PMID- 15581622
TI  - Protein kinase Akt/PKB phosphorylates heme oxygenase-1 in vitro and in vivo.
AB  - Heme oxygenase-1 (HO-1) is a stress response protein that protects cells against
      diverse noxious stimuli. Although regulation of HO-1 occurs mainly at the
      transcriptional level, its posttranslational modifications remain unexplored. We
      have identified a putative consensus sequence for phosphorylation by Akt/PKB of
      HO-1 at Ser188. Recombinant human and rat HO-1, but not mutant HO-1(S188A), are
      phosphorylated in vitro by Akt/PKB. Isotopic 32P-labeling of HEK293T cells
      confirmed that HO-1 is a phosphoprotein and that the basal HO-1 phosphorylation
      is increased by Akt1 activation. HO-1(S188D), a single point mutant equivalent to
      the phosphorylated protein, exhibited over 1.6-fold higher activity than wild
      type HO-1. Fluorescence resonance energy transfer (FRET) studies indicated that
      HO-1(S188D) bound to cytochrome P450 reductase (CPR) and biliverdin reductase
      (BVR) with a slightly lower Kd than wild-type HO-1. Although the changes in
      activity are small, this study provides the first evidence for a role of the
      survival kinase Akt in the regulation of HO-1.

PMID- 15581623
TI  - Specific association of annexin 1 with plasma membrane-resident and internalized
      EGF receptors mediated through the protein core domain.
AB  - Phosphorylation of the Ca2+ and membrane-binding protein annexin 1 by epidermal
      growth factor (EGF) receptor tyrosine kinase has been thought to be involved in
      regulation of the EGF receptor trafficking. To elucidate the interaction of
      annexin 1 during EGF receptor internalization, we followed the distribution of
      annexin 1-GFP fusion proteins at sites of internalizing EGF receptors. The
      observed association of annexin 1 with EGF receptors was confirmed by
      immunoprecipitation. We found that this interaction was independent of a
      functional phosphorylation site in the annexin 1 N-terminal domain but mediated
      through the Ca2+ binding core domain.

PMID- 15581624
TI  - All-trans retinoic acid inhibits proliferation of intestinal epithelial cells by
      inhibiting expression of the gene encoding Kruppel-like factor 5.
AB  - Retinoids are known inhibitors of epithelial cell proliferation. Previous studies
      indicate that Kruppel-like factor 5 (KLF5) is a pro-proliferative transcription
      factor. Here, we examined the effect of all-trans retinoid acid (ATRA) on
      proliferation of the intestinal epithelial cell line, IEC6. Treatment of IEC6
      cells with ATRA inhibited their proliferation due to G1 cell cycle arrest. This
      inhibition was correlated with a decrease in the levels of KLF5 mRNA and promoter
      activity. In contrast, constitutive expression of KLF5 in stably transfected IEC6
      cells with a KLF5-expressing plasmid driven by a viral promoter abrogated the
      growth inhibitory effect of ATRA. Moreover, ATRA inhibited proliferation of
      several human colon cancer cell lines with high levels of KLF5 expression but not
      those with low levels of KLF5 expression. Our results indicate that KLF5 is a
      potential mediator for the inhibitory effect of ATRA on intestinal epithelial
      cell proliferation.

PMID- 15581625
TI  - Asp177 in C4 domain of mouse sphingosine kinase 1a is important for the
      sphingosine recognition.
AB  - Sphingosine kinase (SK) is the enzyme that catalyzes the formation of sphingosine
      1-phosphate (S1P). Although diverse biological functions have been reported for
      SK, its recognition site for its substrate sphingosine (Sph) is still unclear. We
      constructed various mutants of mouse sphingosine kinase 1a (mSK1a), carrying
      mutations in the C4 domain, which we had expected to encompass the Sph-binding
      site. We analyzed the influence of these mutations on the SK activity and
      substrate kinetics. One mutation, Asp177-->Asn177, caused a dramatic decrease in
      SK activity (to approximately 6% of wild type) and an increase in the Km value
      for Sph (10.1-->108 microM), with no change in the affinity for ATP. This result
      suggests that the C4 domain, especially the Asp177, is involved in the specific
      recognition of Sph. In this report, we are able, for the first time, to provide
      an account of the Sph-binding site of SK.

PMID- 15581626
TI  - NF-kappaB activation prevents apoptotic oxidative stress via an increase of both
      thioredoxin and MnSOD levels in TNFalpha-treated Ewing sarcoma cells.
AB  - Repression of activation of c-Jun N-terminal kinase (JNK) participates in the
      anti-apoptotic effect of nuclear factor-kappaB (NF-kappaB) in TNFalpha-treated
      Ewing sarcoma cells. As oxidative stress is one of the most prominent activators
      of JNK, we investigated the relationship between TNFalpha-induced NF-kappaB
      activation and the control of oxidative stress. Inhibition of NF-kappaB
      activation resulted in an increase in TNFalpha-induced ROS production, lipid
      peroxidation and protein oxidation. Those ROS and lipid peroxides were both
      involved in TNFalpha-induced apoptosis, whereas only ROS elevation triggered
      sustained JNK activation. TNFalpha increased the level of two antioxidant
      enzymes, thioredoxin and manganese superoxide dismutase by an NF-kappaB-dependent
      mechanism. Inhibition of expression or activity of these enzymes sensitized cells
      to TNFalpha-induced apoptosis, indicating their functional role in protection
      from cell death. Thus, agents that inhibit activities of these enzymes may prove
      helpful in the treatment of Ewing tumors.

PMID- 15581627
TI  - Organs from mice deleted for NRH:quinone oxidoreductase 2 are deprived of the
      melatonin binding site MT3.
AB  - Two melatonin receptors (MT1 and MT2) have been cloned. A third melatonin binding
      site, MT3, is known with remarkable and distinct pharmacological properties. We
      previously reported the purification of MT3 and identified it as the enzyme
      dihydronicotinamide riboside:quinone reductase 2 (NQO2). To investigate the
      relationship between NQO2 and MT3, we generated a NQO2-/- mouse strain. These
      mice no longer present MT3 binding sites as measured with 2-[125I]-iodo, 5
      methoxycarbonylamino-N-acetyltryptamine, the specific MT3 radioligand. These data
      establish NQO2 as part of the MT3 binding sites in vivo and resolve the matter of
      the nature of the third melatonin binding site.

PMID- 15581628
TI  - Modulation of botulinum neurotoxin A catalytic domain stability by tyrosine
      phosphorylation.
AB  - Botulinum neurotoxin A (BoNT A) is a substrate of the Src family of tyrosine
      kinases. Here, we report that the BoNT A light chain (LC) is phosphorylated in
      the tyrosine-71 located at N-terminus. Covalent modification of this residue
      notably increases the thermal stability of the endopeptidase activity, without
      affecting its catalytic efficacy. Similarly, mutation of this residue
      specifically affected the protein stability but not its endopeptidase function.
      Fusion of the Tat-translocating domain to the N-terminus of the enzyme produced a
      cell permeable, functional enzyme, as evidenced by immunocytochemistry and by the
      cleavage of cytosolic SNAP25 in intact PC12 cells. Noteworthy, truncation of
      cellular SNAP25 was reduced in cells when the Src kinase activity was inhibited
      with a specific antagonist, implying that tyrosine phosphorylation of BoNT A LC
      modulates the in vivo proteolytic activity of the neurotoxin. Taken together,
      these findings substantiate the tenet that tyrosine phosphorylation of BoNT A LC
      could be an important modulatory strategy of the neurotoxin stability and suggest
      that the phosphorylated neurotoxin may be a relevant molecule in vivo.

PMID- 15581629
TI  - Enhancing the first enzymatic step in the histidine biosynthesis pathway
      increases the free histidine pool and nickel tolerance in Arabidopsis thaliana.
AB  - Naturally selected nickel (Ni) tolerance in Alyssum lesbiacum has been proposed
      to involve constitutively high levels of endogenous free histidine. Transgenic
      Arabidopsis thaliana expressing a Salmonella typhimurium ATP phosphoribosyl
      transferase enzyme (StHisG) resistant to feedback inhibition by histidine
      contained approximately 2-fold higher histidine concentrations than wild type
      plants. Under exposure to a toxic Ni concentration, biomass production in StHisG
      expressing lines was between 14- and 40-fold higher than in wild-type plants.
      This suggested that enhancing the first step in the histidine biosynthesis
      pathway is sufficient to increase the endogenous free histidine pool and Ni
      tolerance in A. thaliana.

PMID- 15581630
TI  - Reduction of mitochondrial tRNALeu(UUR) aminoacylation by some MELAS-associated
      mutations.
AB  - The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA.
      Five single nucleotide substitutions within the human mitochondrial tRNALeu(UUR)
      gene have been reported to be associated with MELAS. Here, we provide in vitro
      evidence that the aminoacylation capacities of these five hmtRNALeu(UUR)
      transcripts are reduced to different extents relative to the wild-type
      hmtRNALeu(UUR) transcript. A thermal denaturation experiment showed that the
      A3243G and T3291C mutants, which were the least charged by LeuRS, have fragile
      structures. In addition, the T3291C mutant can inhibit aminoacylation of the wild
      type hmtRNALeu(UUR), indicating that it may act as an inhibitor in the
      mitochondrial heteroplasmic environment.

PMID- 15581631
TI  - Volatile anesthetic modulation of oligomerization equilibria in a hexameric model
      peptide.
AB  - To determine if occupancy of interfacial pockets in oligomeric proteins by
      volatile anesthetic molecules can allosterically regulate oligomerization
      equilibria, variants of a three-helix bundle peptide able to form higher
      oligomers were studied with analytical ultracentrifugation, hydrogen exchange and
      modeling. Halothane shifted the oligomerization equilibria towards the oligomer
      only in a mutation predicted to create sufficient volume in the hexameric pocket.
      Other mutations at this residue, predicted to create a too small or too polar
      pocket, were unaffected by halothane. Inhaled anesthetic modulation of
      oligomerization interactions is a novel and potentially generalizable biophysical
      basis for some anesthetic actions.

PMID- 15581632
TI  - Mistargeted MRPdeltaF728 mutant is rescued by intracellular GSH.
AB  - The most common cystic fibrosis-causing mutation is the deletion of the widely
      conserved phenylalanine 508 (DeltaF508) of CFTR. The mutant is unable to fold
      correctly and to transit to the plasma membrane. MRP1 belongs to the same
      subfamily of ABC proteins as CFTR and confers resistance to a wide range of
      chemotherapeutic drugs. By analogy, phenylalanine 728 was deleted in MRP1. Our
      results shown that MRPDeltaF728 is correctly targeted to the plasma membrane,
      actively transports doxorubicin (DOX) and vincristine (VCR) and shares a
      structure identical to MRP1. Intracellular GSH depletion however results in a
      mistargeted mutant that is retained into the cytoplasm, while in the same
      conditions wild-type MRP1 is correctly routed to the plasma membrane. The GSH
      protein complex could adopt a stable conformation protected against proteolytic
      degradation and correctly targeted to the plasma membrane.

PMID- 15581633
TI  - Decreased cellular permeability to H2O2 protects Saccharomyces cerevisiae cells
      in stationary phase against oxidative stress.
AB  - The higher resistance of stationary-phase Saccharomyces cerevisiae to H2O2 when
      compared with exponential phase is well characterized, but the molecular
      mechanisms underlying it remain mostly unknown. By applying the steady-state H2O2
      delivery model, we show that (a) cellular permeability to H2O2 is five times
      lower in stationary--than in exponential phase; (b) cell survival to H2O2
      correlates with H2O2 cellular gradients for a variety of cells; and, (c) cells in
      stationary phase are predicted to be more susceptible to intracellular H2O2 than
      in exponential phase. In conclusion, limiting H2O2 diffusion into cells is a key
      protective mechanism against extracellular H2O2.

PMID- 15581634
TI  - A novel first exon of the Patched1 gene is upregulated by Hedgehog signaling
      resulting in a protein with pathway inhibitory functions.
AB  - Patched homolog 1 (PTCH1) is a key component of the Hedgehog (HH) signaling
      pathway with three alternative first exons, but only exon 1B transcription
      depending on HH activation. Here, we show that in both human and mouse a novel
      PTCH1 first exon (1C) is expressed. Exon 1C transcription is upregulated by HH
      signaling, but the resulting PTCH1-1C protein has a lower capacity for pathway
      inhibition than PTCH1-1B.

PMID- 15581635
TI  - Functional properties of the alternative NADH:ubiquinone oxidoreductase from E.
      coli through comparative 3-D modelling.
AB  - The alternative NADH:ubiquinone oxidoreductase (NDH-2) from Escherichia coli is a
      membrane protein playing a prominent role in respiration by linking the reduction
      of NADH to the quinone pool. Remote sequence similarity reveals an evolutionary
      relation between alternative NADH:quinone oxidoreductases and the SCOP-family
      "FAD/NAD-linked reductases". We have created a structural model for NDH-2 from E.
      coli through comparative modelling onto a template from this family. Combined
      analysis of our model and sequence conservation allowed us to include the
      cofactor FAD and the substrate NADH in atomic detail. Furthermore, we propose the
      most plausible orientation of NDH-2 relative to the membrane and specify a region
      of the protein potentially involved in ubiquinone binding.

PMID- 15581636
TI  - Oxidized LDL triggers phosphatidylserine exposure in human monocyte cell lines by
      both caspase-dependent and -independent mechanisms.
AB  - Monocytic cell lines have been extensively used to characterize and model various
      features of the atherogenic process. We found striking differences in the
      apoptotic pathways of U937 cells and THP-1 cells exposed to copper-oxidized LDL.
      While phosphatidylserine exposure occurred in both lines, caspase activation was
      only apparent in the THP-1 cells. OxLDL caused caspase activity to decrease below
      that seen in untreated U937 cells, and this corresponded with a loss in
      intracellular thiols. In conclusion, exposure of U937 cells to oxLDL did not
      trigger a conventional apoptosis response, but still resulted in
      phosphatidylserine externalization.

PMID- 15581637
TI  - The b1 isoform of protocadherin-gamma (Pcdhgamma) interacts with the microtubule
      destabilizing protein SCG10.
AB  - Due to their structural characteristics and their diversity, the 22 members of
      the protocadherin-gamma (Pcdhgamma) family have been suggested to contribute to
      the establishment of specific connections in the nervous system. Here, we focus
      on a single isoform, Pcdhgamma-b1. Its expression is found in different brain
      regions and in developing spinal cord it is restricted to scattered cells,
      whereas all cells are labeled using an antibody that recognizes all Pcdhgamma
      isoforms. As a first step to understanding the signaling mechanisms downstream of
      Pcdhgamma, we identify the microtubule-destabilizing protein SCG10 as a
      cytoplasmic interactor for Pcdhgamma-b1 and other isoforms of the Pcdhgamma-b
      subfamily, and show that SCG10 and Pcdhgamma-b1 are found together in certain
      neuronal growth cones.

PMID- 15581638
TI  - Post-transcriptional effects of phorbol 12-myristate 13-acetate on transcriptome
      of U937 cells.
AB  - To identify post-transcriptionally modulated genes at the translational level by
      phorbol 12-myristate 13-acetate (PMA), we investigated mRNA profiles in the
      polysomal and the cytoplasmic fractions of U937 cells before and after PMA
      stimulation using microarrays with 15017 oligonucleotide probes. Global
      comparison of the profiles showed that the cytoplasmic distribution of mRNAs was
      considerably modulated upon PMA stimulation. The results also indicate that PMA
      post-transcriptionally regulated at least 0.7% of detectable genes in U937 cells.
      Thus, besides transcriptional modulation by PMA, changes in the translational
      state of transcripts seem to play a critical role in PMA-induced differentiation
      of U937 cells.

PMID- 15581639
TI  - Redox behaviour of the haem domain of flavocytochrome c3 from Shewanella
      frigidimarina probed by NMR.
AB  - Flavocytochrome c3 from Shewanella frigidimarina (fcc3) is a tetrahaem
      periplasmic protein of 64 kDa with fumarate reductase activity. This work reports
      the first example of NMR techniques applied to the assignment of the
      thermodynamic order of oxidation of the four individual haems for such large
      protein, expanding its applicability to a wide range of proteins. NMR data from
      partially and fully oxidised samples of fcc3 and a mutated protein with an axial
      ligand of haem IV replaced by alanine were compared with calculated chemical
      shifts, allowing the structural assignment of the signals and the unequivocal
      determination of the order of oxidation of the haems. As oxidation progresses the
      fcc3 haem domain is polarised, with haems I and II much more oxidised than haems
      III and IV, haem IV being the most reduced. Thus, during catalysis as an electron
      is taken by the flavin adenosine dinucleotide from haem IV, haem III is eager to
      re-reduce haem IV, allowing the transfer of two electrons to the active site.

PMID- 15581640
TI  - Identification of a cysteine residue important for the ATPase activity of C.
      elegans fidgetin homologue.
AB  - Based on the amino acid alignment, Caenorhabditis elegans F32D1.1 was identified
      to be a homologue of the mammalian fidgetin. We produced and purified the F32D1.1
      protein by using a baculovirus-expression system. F32D1.1 has an ATPase activity,
      which is sensitive to N-ethylmaleimide. Km and Vmax for the ATPase activity of
      F32D1.1 were estimated to be 0.44 mM and 225 nmol/mg/min, respectively. When the
      cysteine at the position of 368 was mutated to alanine, the ATPase activity was
      greatly decreased; Vmax was decreased to one-sixth, while Km remained similar.
      These results suggest that the unique position of cysteine 368, located
      immediately downstream of the Walker A motif, plays an important role in the ATP
      hydrolysis process of C. elegans F32D1.1 protein.

PMID- 15581641
TI  - Identification of a putative p53 binding sequence within the human mitochondrial
      genome.
AB  - A small fraction of the total cellular amount of nuclear transcription factor p53
      seems to be located at and within mitochondria. Transcription factors of the
      steroid receptor superfamily that, like p53, lack a classical mitochondrial
      leader sequence are nonetheless imported into mitochondria where they regulate
      mtDNA transcription through binding to specific recognition sequences. Here, we
      examined seven candidate sequences from the human mitochondrial genome with
      similarity to the consensus p53 binding motif. Two imperfect half-sites at
      coordinate 1553 with homology to the nuclear IGF-BP3 box A binding sequence are
      demonstrated to confer responsivity to p53 and the p53 relatives p73alpha and
      beta in the context of the cell nucleus. Mitochondrial p53 may thus bind directly
      to mtDNA and, perhaps, be involved in the regulation of mitochondrial
      transcription/replication.

PMID- 15581642
TI  - Stress, fibromyalgia, and sleep.

PMID- 15581643
TI  - Work stress and incidence of newly diagnosed fibromyalgia: prospective cohort
      study.
AB  - OBJECTIVES: We examined the prospective association between occupational stress
      and incidence of newly diagnosed fibromyalgia. METHODS: Cohort study with
      questionnaire surveys in 1998 and 2000 completed by 4791 hospital employees (4250
      women and 541 men). Stress, as indicated by high workload, low decision latitude,
      and being a victim of workplace bullying, was assessed in the first survey.
      Incident cases (n=47) were employees reporting physician-diagnosed fibromyalgia
      in 2000 but not in 1998. Covariates were sex, age, income, obesity, and smoking.
      RESULTS: After adjustment for covariates, the odds ratio of incident diagnosed
      fibromyalgia for workplace bullying was 4.1 (95% CI 2.0-9.6). The corresponding
      odds ratios for high workload and low decision latitude were 2.1 (1.2-3.9) and
      2.1 (1.1-4.0), respectively. CONCLUSION: Stress seems to be a contributing factor
      in the development of fibromyalgia, but further research is needed to examine
      whether stress perceptions are affected by undiagnosed fibromyalgia.

PMID- 15581644
TI  - Stress and fibromyalgia--what is the link?

PMID- 15581645
TI  - Mental fatigue, work and sleep.
AB  - OBJECTIVE: The study examined the multivariate relationship between mental
      fatigue and different work-related (work load, work hours) and background/life
      style factors, as well as disturbed sleep. METHODS: A total of 5720 healthy
      employed men and women living in the greater Stockholm area participated in a
      questionnaire study on cardiovascular risk factors. The data were analysed using
      a multiple logistic regression analysis with self-rated fatigue as the dependent
      variable. RESULTS: Fatigue was predicted by disturbed sleep (4.31; 3.50-5.45,
      high immersion in work (4.17; 2.93-5.94), high work demands (2.39; 1.54-3.69),
      social support, being a female, being a supervisor and high age. Shift work, work
      hours (including overtime) and influence at work did not become significant
      predictors. With control for work demands a high number of work hours was
      associated with lower fatigue. CONCLUSION: Disturbed sleep is an important
      predictor of fatigue, apparently stronger than previously well-established
      predictors such as work load, female gender, lack of exercise, etc.

PMID- 15581646
TI  - Evaluation of four highly cited energy and fatigue mood measures.
AB  - This paper evaluates four highly cited measures of energy and fatigue moods.
      Substantial experimental and correlational evidence supports the conclusion that
      scores from the vitality scale of the SF-36 Health Survey can provide a valid
      measure of the recalled frequency of month-long feelings of energy and fatigue.
      Substantial experimental and correlational evidence supports the conclusion that
      scores from the fatigue and vigor scales of the Profile of Mood States (POMS) can
      provide reliable and valid measures the intensity of both week-long and "right
      now" fatigue and energy mood states, respectively. A smaller body of evidence
      supports the conclusion that scores from the energy scale of the Activation
      Deactivation Adjective Checklist (AD-ACL) can provide a valid measure of the
      "right now" mood of energy; however, the energy scale of the AD-ACL has several
      limitations compared to the POMS vigor scale. All the measures lacked integration
      within a compelling theory of the mood of energy-fatigue. It is concluded that
      progress in understanding of energy and fatigue mood states will be aided by
      advances in both the psychobiological conceptualization of fatigue and energy
      mood states and their measurement.

PMID- 15581647
TI  - Predictors of outcome in fatigued employees on sick leave: results from a
      randomised trial.
AB  - OBJECTIVE: The main objective of this study was to identify predictors of fatigue
      caseness, work resumption and chronic fatigue syndrome (CFS)-like caseness in a
      sample of fatigued employees on sick leave. METHODS: For 12 months, 151 fatigued
      employees on sick leave, 44% of whom met research criteria for CFS at baseline,
      were followed. Measures included fatigue, health aspects, psychological problems,
      burnout, causal attributions and self-efficacy. Logistic regression analysis was
      used to determine associations between predictor variables at baseline and
      outcome at follow-up. RESULTS: After 12 months, 43% of the patients were no
      longer fatigue cases, and 62% had resumed work. Recovery from fatigue caseness
      was predicted by stronger psychological attributions and other perception-related
      factors, whereas work resumption was predicted by lower age, male sex, CFS-like
      caseness and less cognitive difficulties. Lower physical functioning scores were
      predictive of (the development of) CFS-like caseness. CONCLUSION: Recovering from
      persistent fatigue and work resumption seem to result from different underlying
      processes and do not necessarily fall together. As many factors associated with
      outcome in fatigue reflect illness perception, the prevention of persistent
      fatigue and CFS may partly be achieved by the modification of perception.

PMID- 15581648
TI  - Menstrual cycle influences on pain and emotion in women with fibromyalgia.
AB  - OBJECTIVE: This study examined the influence of the menstrual cycle on pain and
      emotion in women with fibromyalgia (FM) as compared with women with rheumatoid
      arthritis (RA) and to healthy controls. METHODS: One hundred and twenty-five
      premenopausal women (21-45 years old) participated in this study (57 with FM, 20
      with RA, and 48 controls). Pain and emotion assessments were conducted during the
      follicular and the luteal phases of the menstrual cycle. RESULTS: Women with FM
      experienced more pain, menstrual symptoms, and negative affect than did women
      with RA and the controls. All women reported less positive affect during the
      luteal phase, although this pattern was more pronounced in women with FM and RA
      than in controls. CONCLUSION: Although FM pain did not vary across the menstrual
      cycle, these results point to the importance of considering the lower level and
      cyclical nature of positive affect when studying women with chronic pain.

PMID- 15581649
TI  - Sleep disturbances among HIV-positive adults: the role of pain, stress, and
      social support.
AB  - OBJECTIVE: Investigate the relationships between pain, stress, social support,
      and sleep disturbance among a diverse sample of HIV-positive adults. METHOD:
      Participants (N = 146) completed self-report measures on pain, stress, social
      support, and sleep disturbance. CD4 T-cell count was obtained from medical
      records. RESULTS: Greater pain and stress were associated with greater sleep
      disturbance. Greater assistance from friends was associated with greater sleep
      disturbance, whereas greater understanding from friends regarding participants'
      HIV-related stress was associated with less sleep disturbance. CONCLUSION: As
      expected, pain was significantly associated with sleep disturbance. Additionally,
      psychosocial variables were strongly associated with sleep. The type of support
      from friends differentiated whether the support was positively or negatively
      associated with sleep problems. Social support, depending on the type, may not
      always be helpful for adults living with HIV/AIDS. Future studies need to examine
      factors that may mediate the relationship between psychosocial constructs and
      healthy sleep.

PMID- 15581650
TI  - Perceived stress, stress attributions and psychological distress in psoriasis.
AB  - OBJECTIVE: The objective of this study was to measure causal beliefs in
      individuals with psoriasis and to explore their relationship with perceived
      stress, quality of life, psychological well-being and psoriasis severity.
      METHODS: This study was cross-sectional in design, and patients were required to
      complete validated questionnaires assessing perceptions of illness, quality of
      life, psoriasis severity, perceived stress and psychological mood. A total of 141
      individuals were recruited from two settings: an outpatient skin clinic at King's
      College Hospital and the Psoriasis Association. RESULTS: A strong belief in
      stress/psychological attributes as a causal factor was found in 61% of the
      sample. This belief was significantly associated with higher levels of anxiety,
      depression and perceived stress (r > or = .38; P < or = .0001). Perceived stress
      in this sample was significantly associated with a poorer level of quality of
      life, higher levels of anxiety and depression (r > or = .27; P < or = .002) but
      not with psoriasis severity. CONCLUSIONS: The belief that stress is causal was
      associated with lower levels of psychological well-being. However, there was no
      association between perceived stress and more objective measures of psoriasis
      severity.

PMID- 15581651
TI  - Maternal posttraumatic stress response after the birth of a very low-birth-weight
      infant.
AB  - OBJECTIVE: For parents, the premature birth of a child represents a traumatic
      event for which they are poorly prepared. To date, the focus of scientific
      interest has been on maternal psychological stress responses, such as anxiety and
      depression, or on appropriate coping mechanisms, whereas only scant attention has
      been paid to the traumatic aspect of the maternal experience after very low-birth
      weight (VLBW) birth. The present study is the first to investigate the
      posttraumatic stress response of mothers after the birth of a VLBW infant in a
      prospective longitudinal study. METHODS: Fifty mothers of VLBW infants were
      examined at four measuring time points (1-3 days pp, 14 days pp and 6 and 14
      months pp) with respect to posttraumatic symptoms [Impact of Event Scale (IES
      R)], psychiatric diagnosis (SKID I for DSM-IV) and the extent of depression [Beck
      Depression Inventory (BDI) and Montgomery Asberg Depression Scale (MADRS)] and
      anxiety [State-Trait Anxiety Inventory (STAI) and Hamilton Anxiety Scale (HAMA)].
      The control group comprised a group of 30 mothers after the uncomplicated
      spontaneous birth of a healthy child. RESULTS: At all four measuring timepoints
      (except 6 months pp), the mothers of the premature infants recorded significantly
      higher values for traumatic experience and depressive symptoms and anxiety
      compared with the controls. In contrast to the mothers in the control group, the
      mothers of the premature infants displayed no significant reduction in
      posttraumatic symptoms (IES-total), even 14 months after birth. CONCLUSION: The
      results indicate that the situation of a mother who has given birth to a VLBW
      infant is a complex, with long-term traumatic event necessitating ongoing
      emotional support extending beyond the period immediately after the birth.

PMID- 15581652
TI  - The measurement of coping responses: validity of the Billings and Moos Coping
      Checklist.
AB  - OBJECTIVE: The primary aim of the study was to investigate the factor structure
      and psychometric properties of the modified Coping Checklist. METHODS: Self
      report questionnaires asking about coping responses and mental health were
      administered to 515 undergraduate university students and to 119 patients
      awaiting elective coronary artery bypass graft surgery. Confirmatory (CFA) and
      exploratory factor analyses (PCA) were used to summarize and describe coping
      responses. RESULTS: CFA indicated that the subscale structure originally proposed
      for the Coping Checklist did not adequately fit the data. Subsequent PCA resulted
      in four factors: (1) Positive reappraisal; (2) Seeking support; (3) Avoidance;
      and (4) Information seeking. Internal consistencies ranged between .41 and .62
      and 12-week test-retest reliability ranged between .59 and .71. Evidence for the
      concurrent validity of the solution generated by PCA was demonstrated by low to
      moderate correlations between the four factors identified and demographic and
      psychosocial measures. CONCLUSION: Even with modifications to the Coping
      Checklist, it is recommended that researchers investigate alternative methods of
      assessing coping responses in health psychology settings.

PMID- 15581653
TI  - The associations between childhood dance participation and adult disordered
      eating and related psychopathology.
AB  - OBJECTIVE: To examine the relationship between childhood dance participation and
      adult eating behavior and psychological health. METHODS: A total of 546
      undergraduate females at a large Midwestern university completed questionnaires
      regarding eating behavior and associated features, depression, self-esteem, and
      body image. RESULTS: Women who participated in childhood dance are more likely to
      score higher on measures of bulimic behaviors than nondancers. In addition,
      childhood dancers indicated greater drive for thinness and poorer impulse control
      compared to nondancers. Furthermore, there was a statistical trend for childhood
      dancers to report greater perfectionism and a smaller ideal body mass than
      nondancers. There were no significant differences between dance groups on
      measures of depression and self-esteem. CONCLUSION: These findings suggest that
      participating in dance as a child may influence one's eating behavior as an
      adult, including associated factors such as drive for thinness and impulse
      control and potentially perfectionism and preferred body size.

PMID- 15581654
TI  - Hostility differentially predicts cardiovascular risk factors in African American
      and White young adults.
AB  - OBJECTIVE: Hostility may influence racial disparities in cardiovascular disease
      through differential associations with cardiovascular risk factors. This study
      explored racial variations in relations between hostility and selected
      cardiovascular risk factors. METHODS: Cook-Medley Hostility (Ho) scores and 11
      risk factors were examined among 66 healthy, White and African American young
      adults. RESULTS: Controlling for age, gender, and body mass index, the
      interaction of hostility and race yielded significant (or marginal) associations
      with resting systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI;
      i.e. cardiac output adjusted for body size), total peripheral resistance (TPR),
      insulin (INS), triglycerides (TG) and percent body fat (PBF). Contributing
      substantial variance, hostility was positively associated with SBP, DBP, TPR, TG
      and INS, and negatively associated with CI among African Americans. Conversely,
      hostility was negatively associated with TPR and PBF among Whites. CONCLUSION:
      Hostility may confer greater cardiovascular risk among young African Americans
      than Whites.

PMID- 15581655
TI  - The question of quality of life in fibromyalgia patients.

PMID- 15581656
TI  - A randomised, controlled, triple-blind trial of the efficacy of homeopathic
      treatment for chronic fatigue syndrome.

PMID- 15581658
TI  - Acute heat stress induces jumping escape behavior in mice.
AB  - A new heat escape behavior was revealed in mice (ddY mice) under acute heat
      stress conditions. Mice in a fully covered cage were exposed to 24, 34, 37 and
      38.5 degrees C for 60 min. Rectal temperature increased in conditions above 34
      degrees C. Furthermore, serum osmolality and body weight loss also increased in
      conditions above 37 degrees C. At above 37 degrees C, a large number of mice
      attempted to escape from the partially covered cage, and so exhibited jumping
      behavior during a period of 60 min. However, mice exposed to 24 and 34 degrees C
      did not exhibit such behavior. These results indicated that acute heat stress
      above 37 degrees C induced evaporative water loss and jumping escape behavior in
      mice.

PMID- 15581659
TI  - Effects of chronic ICV leptin infusion on motor-activating effects of D
      amphetamine in food-restricted and ad libitum fed rats.
AB  - Recently, attention has turned to the possibility that endocrine adiposity
      hormones, such as leptin, may regulate appetitively motivated behavior by
      modulating brain dopamine function. By extension, it has been hypothesized that
      the increased behavioral sensitivity of food-restricted, underweight rats to
      psychostimulant challenge may be triggered by the accompanying hypoleptinemia.
      The purpose of the present study was to determine whether two weeks of continuous
      intracerebroventricular (ICV) infusion of leptin alters the motor-activating
      effect of D-amphetamine (0.75 mg/kg, IP) in food-restricted rats. Lateral
      ventricular infusion of leptin, using a regimen that decreases food intake and
      body weight in ad libitum fed rats (12 microg/day), had no effect on the
      locomotor response to D-amphetamine in food-restricted rats that were maintained
      at 80% of prerestriction body weight. This result may indicate that
      hypoleptinemia is not involved in the induction/maintenance of neuroadaptations
      that mediate enhanced behavioral sensitivity to psychostimulant challenge.
      Interestingly, ad libitum fed rats treated with leptin displayed an increased
      locomotor response to D-amphetamine that was most prominent 3-5 days after
      termination of the infusion. Body weights and D-amphetamine sensitivity of these
      subjects returned to control values by 8-10 days postinfusion. The enhanced
      behavioral sensitivity to D-amphetamine in leptin-treated ad libitum fed rats may
      be a by-product of adipose depletion and, if so, would further support
      involvement of a peripheral signal other than hypoleptinemia in the modulation of
      central sensitivity to psychostimulant challenge.

PMID- 15581660
TI  - Cognitive and emotional alterations in periadolescent mice exposed to 2 g
      hypergravity field.
AB  - The development of the nervous system is a dynamic process where epigenetic
      factors play a fundamental role. Both ground-based and space research indicate
      that exposure to an altered gravitational environment affects rodent
      neurobehavioral profile and stage of development as well as duration of exposure
      appear to be critical for the observed effects. The behavioral profile of
      adolescent (28-day-old) male and female CD-1 mice upon acute 2 g exposure was
      characterized and emotional/anxiety responses (plus-maze), as well as spatial
      learning performance (Morris water-maze), were assessed respectively 24 and 48 h
      after hypergravity exposure. Behavioral observation indicated a transient mild
      sickness associated with hypergravity, with a decrease in spontaneous activity.
      Rotation per se induced an increase in emotional/anxious responses and a
      deterioration of spatial learning acquisition, while hypergravity specifically
      improved flexibility of spatial orientation.

PMID- 15581661
TI  - Mitochondrial complex I inhibition depletes plasma testosterone in the rotenone
      model of Parkinson's disease.
AB  - Age-related depletion of testosterone may increase the brain's vulnerability to
      parkinsonian- or Alzheimer's-like neurodegenerative disorders. In rats, rotenone,
      a mitochondrial complex I inhibitor, causes specific nigral dopaminergic
      neurodegeneration producing parkinsonian symptoms. In this study, rotenone was
      administered on a daily basis (2 mg/kg i.p.) to two groups of rats, over a period
      of 30 and 60 days, respectively. In order to contribute towards the validation of
      the rotenone rat model, the changing level of the peripheral sex steroid hormone,
      testosterone, which would also mimic those found in Parkinson's disease (PD)
      patients, was evaluated. Parallel to this, prolactin, luteinizing hormone (LH),
      the nonsexual steroid thyroid-stimulating hormone, and the corticosterone hormone
      levels in the peripheral blood plasma were measured to show whether other
      hormones have also been affected by complex I inhibition. The rotenone treatment
      caused a decrease of testosterone level in the peripheral blood plasma. There
      were no differences in the thyroid hormone and prolactin but increases in
      leutinizing hormone and corticosterone were observed. Data from this study
      indicate that rotenone depleted the sex steroid hormone which is preferentially
      produced in the periphery, e.g., adrenal gland and testis. In conclusion, because
      a decrease in testosterone levels is also one of the comorbidities which are
      found in male PD patients, our results indicate that the rotenone model mimics PD
      symptoms not only on a neuronal and behavioral level, but also on the
      testosterone levels.

PMID- 15581662
TI  - Long-lasting, selective, anxiogenic effects of feline predator stress in mice.
AB  - Lasting increases in anxiety-like behavior (ALB) are produced by brief exposure
      of rats to a cat [Adamec RE, Shallow T, Lasting effects on rodent anxiety of a
      single exposure to a cat, Physiol. Behav., 54 (1993) 101-109.]. Mice also respond
      defensively to natural predator stimuli. Moreover, chronic exposure of mice to
      rat odor has immediate anxiogenic effects in plus maze and lasting (7 days) and
      effects on acoustic startle. The present study examined the lasting (7 days)
      after effects on ALB of a brief unprotected exposure of male CFW mice to a cat.
      Lasting effects on ALB of exposure to the cat exposure room were also assessed.
      Effects on behavior were studied in the hole board and elevated plus-maze (EPM).
      An ethological analysis of behavior revealed that risk assessment in the EPM was
      increased the most in predator-stressed mice. Mice exposed to the cat exposure
      room showed increased risk assessment falling between controls and cat exposed
      mice. Behavior in the hole board was unaffected, as were most other behaviors in
      the plus maze. Factor analysis revealed independence of risk assessment from
      other measures of ALB, activity and exploration, consistent with findings in
      rats. Aspects of the stress experience were highly predictive of later response
      to the cat. Cat biting and pawing, mouse fleeing and mouse weight measured at the
      time of cat exposure together accounted for 71% of the variance of risk
      assessment in cat exposed mice. The significance of these findings for
      vulnerability to cat predator stress of mice and for the use of predator stress
      in mice as a model of aspects of posttraumatic stress disorder (PTSD) are
      discussed.

PMID- 15581663
TI  - Effects of acute stressors on nociception, adrenocortical responses and behavior
      of dairy cows.
AB  - Effects of acute stressors on behavioral, adrenocortical and nociceptive
      responses were examined in 24 dairy cows kept in tie stalls, using 15 min of
      social isolation in novel surroundings (ISOL), fixation by the head in the home
      stall (FIX) and the provision of novel neighbors/stall (NEIGH) as acute stressors
      as well as a control treatment (CON). Each cow was exposed to one treatment daily
      in a balanced order. All stressors led to signs of hypoalgesia as indicated by
      slower (P=0.01) and reduced responses (P<0.10) toward nociceptive laser
      stimulation after exposure to the acute stressors. ISOL, however, had stronger
      effects than FIX or NEIGH. ISOL or FIX led to increased plasma concentration of
      cortisol (P<0.001), whereas NEIGH or CON did not. The behavioral responses were
      affected by treatments as well, as shown by decreased rumination for all
      stressors (P<0.001) and a gradual increase in active avoidance from CON to NEIGH
      to FIX (P<0.001). Furthermore, exposure to NEIGH led to increased exploration
      (P<0.001), aggression (P<0.10) and self-grooming behavior (P<0.10) compared with
      the CON treatment. The results suggest that nociceptive changes are part of
      responses toward acute stress in dairy cows. The nociceptive changes, however,
      were not direct reflections of the adrenocortical or behavioral responses toward
      the acute stressors. Therefore, quantification of nociceptive changes, in
      combination with behavioral and physiological registrations, can be one way to
      broaden the range of biological systems, considered for the study of animals
      under stress, and thereby extend the understanding of responses toward acute
      stress in dairy cows.

PMID- 15581664
TI  - Sweet and sour preferences in young children and adults: role of repeated
      exposure.
AB  - We investigated the influence of repeated exposure to orangeades with added
      sucrose and different concentrations of citric acid, on the taste preferences of
      6- to-11-year-old children and young adults. During an intervention study of 8
      days, 59 children (9.2+/-0.9 years) and 46 young adults (22+/-2.0 years)
      received, each day, either an orangeade with a sweet taste, a sour taste, or no
      orangeade (control). Before (baseline) and after the intervention, preferences
      for a series of orangeades and yoghurt, which varied in balance of sweet and sour
      tastes, were measured by means of a rank-ordering procedure. The variation in
      balance of sweet and sour taste was established by adding different amounts of
      citric acid (orangeade: 0.009, 0.013, 0.020, 0.029, 0.043, and 0.065 M added
      citric acid; yoghurt: 0.027, 0.038, 0.056, 0.081, 0.12, and 0.17 M added citric
      acid) to a stock orangeade and yoghurt with 0.42 M sucrose. The sweet and sour
      tasting orangeade that were consumed during the intervention were equally
      preferred at baseline. After an 8-day exposure to the sweet orangeade, children's
      preferences for this orangeade (0.42 M sucrose) significantly increased (p<0.05).
      A similar trend was observed for the yoghurt with 0.42 M sucrose (p=0.09). An 8
      day exposure to the sour orangeade did not have a significant effect on
      children's preference for this orangeade. The taste preferences of adults did not
      change after the intervention. The control group of children and adults did not
      show any change in preferences for sweet and sour tastes. Future research is
      needed to investigate whether the changed preferences for sweet taste are stable
      over time and how these changed taste preferences are related to a change in the
      consumption of sugar rich foods.

PMID- 15581665
TI  - Swallowing threshold and masticatory performance in dentate adults.
AB  - A variety of both natural and artificial foods are commonly used for the
      evaluation of masticatory function. We compared swallowing thresholds of three
      natural foods (peanuts, cheese and carrots) to those of a standardized artificial
      test food (Optocal Plus) and examined the relationship between masticatory
      performance and the swallowing threshold. Eighty-seven healthy dentate subjects
      participated (25 men and 62 women, aged 42.0+/-12.1 years). We evaluated the
      dental state, registered the number of chewing strokes used before swallowing,
      analyzed the chewed particles and determined median particle sizes (X50) for
      Optocal Plus after 15 chewing strokes and at the moment of swallowing. The
      results show that the number of strokes used before swallowing each natural food
      linearly increased with volume (P<0.001), and that carrots required more strokes
      than peanuts and cheese (P<0.001). The number of chewing strokes used before
      swallowing Optocal Plus was comparable to the number used for carrots.
      Masticatory performance was significantly influenced by dental state, but not by
      age or gender. Significant correlations were observed for: (1) the number of
      chewing strokes used before swallowing natural foods and Optocal Plus; (2) the
      median particle sizes after 15 strokes and before swallowing; (3) the number of
      chewing strokes before swallowing and the corresponding median particle size.
      However, median particle sizes as obtained after 15 strokes did not correlate
      with the number of strokes used before swallowing (r=0.02). Thus, bad chewers did
      not necessarily chew longer before swallowing than good chewers. As a consequence
      bad chewers would, on average, swallow larger food particles.

PMID- 15581666
TI  - Intensity of aggressive interactions modulates testosterone in male marmosets.
AB  - Androgen is associated with the expression of male-typical behavior, including
      aggressive behavior, but high levels of androgen may be incompatible with other
      behavioral systems, such as paternal care. In a variety of species of birds that
      display paternal care, testosterone (T) levels in males are maintained at low
      levels, and these levels rise only in response to direct agonistic challenges.
      This idea has not been thoroughly studied in mammals with biparental care, and we
      exposed male marmosets (Callithrix kuhlii), a monogamous and biparental primate
      to aggressive interactions with unfamiliar intruders. Urinary levels of T and
      cortisol (CORT) were monitored prior to and following these interactions.
      Baseline T was not correlated with variation in aggression in either residents or
      intruders, and CORT was not affected by the encounters. However, males responded
      to an encounter with male intruders with changes in T that correlated with the
      level of aggression displayed by the resident male during the trial. Encounters
      with male intruders that elicited high frequencies of aggressive displays by the
      male resident were associated with increased T 2-6 h and 24 h following the
      encounter, and encounters that had few aggressive displays resulted in no change
      or a decrease in T concentrations. Intruders did not demonstrate a significant
      relationship between T and aggression. Thus, the magnitude of the hormonal
      response is dependent on the intensity of aggression during a male-male
      encounter, suggesting that elevated androgens are likely to be a consequence,
      rather than a cause, of aggressive interactions in marmosets.

PMID- 15581667
TI  - Housing conditions influence the expression of food-anticipatory activity in
      mice.
AB  - If food is presented for a limited duration once every 24 h, rats will gradually
      develop increased activity in the hours preceding mealtime, even if this is
      during a time of day when they are normally inactive. This food-anticipatory
      activity (FAA) is mediated by the entrainment of an endogenous self-sustaining
      circadian pacemaker. Mice are increasingly being used for the molecular analysis
      of behavior because of the large number of genetically manipulated mouse models
      available, but little is known about food entrainment in this species. This study
      assessed the impact of different housing conditions on the expression of FAA in a
      temporally restricted feeding paradigm. Wheel-running activity rhythms were
      recorded from mice (Mus musculus) undergoing food restriction while housed under
      one of two conditions. The results demonstrated that mice housed on open shelves
      showed robust FAA while those housed in isolation boxes did not. These results
      indicate that differences in susceptibility to food entrainment among mice (e.g.,
      those with different genotypes) should be interpreted cautiously, since at least
      one strain is strongly affected by a relatively minor procedural difference that
      was not anticipated to have a significant impact.

PMID- 15581668
TI  - Activity-induced GLP-1 release in lean and obese subjects.
AB  - The aim of the study was to determine whether physical activity stimulates GLP-1
      release on the short-term in normal weight and in obese subjects compared to rest
      and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity
      in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22.9+/-1.4; age 35+/
      12.7), as well as obese subjects (n=27; 21 males, 6 females; BMI 30.9+/-2.7; age
      47.1+/-11.86) were tested in a resting and a physical activity condition. Obese
      subjects were matched over two groups for a weight loss period of 3 months. After
      weight loss, the tests were repeated. The area under the curve (AUC pmol/lxmin)
      for GLP-1 concentrations was significantly increased in the physical activity
      condition compared to rest in lean subjects (P=0.05) as well as in the obese
      subjects after weight loss (P<0.05), but not in the obese subjects before weight
      loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after
      a weight loss period supports the idea of a neuroendocrine loop in addition to
      distal-intestinal stimulation of GLP-1 release. Modest weight loss might be
      effective for increasing GLP-1 sensitivity to acute stimulation.

PMID- 15581669
TI  - Modulation of physiological brain hyperthermia by environmental temperature and
      impaired blood outflow in rats.
AB  - To study the role of ambient temperature and brain blood outflow in modulating
      physiological brain hyperthermia, temperatures in two brain structures (nucleus
      accumbens or NAcc and hippocampus or Hippo) and a non-locomotor head muscle
      (musculus temporalis) were monitored in rats exposed to three arousing stimuli
      (placement in the cage or environmental change, 3-min social interaction with a
      female rat, 3-min innocuous tail-pinch) under three conditions (intact animals at
      23 degrees C or control, intact animals at 29 degrees C, animals with chronically
      occluded jugular veins at 23 degrees C). While each stimulus in each condition
      induced hyperthermia, with more rapid and stronger changes in brain structures
      than muscle, there were significant differences between conditions. At 29 degrees
      C, animal placement in the cage resulted in stronger temperature increase and
      larger brain-muscle differentials, while basal temperatures in Hippo and muscle
      (but not in NAcc) were higher than control. At 29 degrees C, hyperthermia during
      social interaction was smaller but more prolonged, while the response to tail
      pinch was similar to that seen at normal environmental temperatures. Animals with
      chronically occluded jugular veins had similar basal temperatures but showed much
      weaker hyperthermia than intact animals during each stimulus presentation;
      temperature increases in brain structures, however, were much stronger than in
      the muscle. Our data suggest that the brain is able to decrease neural activation
      induced by environmental challenges under conditions of impaired blood outflow
      and restricted heat dissipation to the external environment.

PMID- 15581670
TI  - Prolyl-leucyl-glycinamide shares some effects with oxytocin but decreases
      oxytocin levels.
AB  - Oxytocin treatment in rats induces long-lasting antistress and growth promoting
      effects. This study investigated whether prolyl-leucyl-glycinamide (PLG) (the c
      terminal tripeptide of oxytocin) or tocinoic acid (the ring structure of
      oxytocin) could induce some of these effects in male rats. For this purpose, PLG
      (2 or 10 mg/kg, s.c.) or tocinoic acid (1 mg/kg, s.c.) was administered to rats
      once a day for 3 or 5 days. Blood pressure, heart rate, spontaneous motor
      activity, nociceptive thresholds, and the survival of ischaemic musculocutaneous
      flaps were measured. In addition, endogenous oxytocin levels and plasma levels of
      some hormones known to be influenced by oxytocin were determined. PLG (2 mg/kg,
      s.c., but not 10 mg/kg, s.c.) decreased diastolic blood pressure (p<0.05) and
      locomotor activity (p<0.05). PLG (10 mg/kg, s.c.) decreased gastrin (p<0.05) and
      endogenous oxytocin levels in plasma (p<0.01). Tocinoic acid decreased locomotor
      activity (p<0.05), but did not affect any of the other parameters measured. In
      conclusion, this study showed that both PLG and tocinoic acid decrease locomotor
      activity. In addition, PLG also induced some other effects similar to those
      induced by oxytocin treatment but when administered in high doses it decreased
      oxytocin levels.

PMID- 15581671
TI  - Preserved LTP and water maze learning in hyperglycaemic-hyperinsulinemic ZDF
      rats.
AB  - Previous investigations have demonstrated that cognitive deficits as well as
      hippocampal dysfunctions are generated in animals presenting manifestations of
      Type 1 diabetes (T1D) mellitus. The present study examined whether such deficits
      can also be reproduced in the Zucker Diabetic Fatty (ZDF) rats after they
      developed symptoms of Type 2 diabetes (T2D). Learning and memory assessments were
      performed using the Morris water maze 5 weeks after the animals presented
      symptoms of Type 1 diabetes for Experiment 1 (Exp 1) and after 8 weeks for
      Experiment 2 (Exp 2). Testing in the water maze revealed that ZDF rats learned
      the task normally, although control rats were found to swim significantly faster
      after 5 or 8 weeks of untreated diabetes. From an electrophysiological
      perspective, we observed that the integrity of synaptic function was also
      preserved in ZDF rats as no alterations in long-term potentiation (LTP) were
      observed in the area CA1 of hippocampal slices. It is concluded that
      hyperglycaemia is not the only factor influencing water maze learning and LTP in
      this animal model of Type 2 diabetes (T2D). The experiments suggest that the
      resistance of ZDF rats to cognitive and electrophysiological dysfunctions might
      be related to the protective action of hyperinsulinemia. Indeed, measurements of
      the plasma insulin level at the end of testing were significantly superior in ZDF
      rats in comparison to control rats.

PMID- 15581672
TI  - A profile of the immediate endocrine, metabolic and behavioural responses
      following a dual exposure to endotoxin in early life.
AB  - Dual exposure to endotoxin on postnatal days (PNDs) 3 and 5 is increasingly being
      used to model the impact of bacterial challenge, in early life, on long-term
      health outcomes. Currently, however, little is known about how exposure to
      endotoxin using this model disrupts systems known to program physiological
      alterations in later life. The aim of the current study was to define, in Fischer
      344 rat pups, a framework of the immediate endocrine, metabolic, and behavioural
      consequences following challenge with 0.05 mg/kg of endotoxin (Salmonella
      enteritidis) on PNDs 3 and 5. Circulating corticosterone in endotoxin challenged
      neonates was significantly elevated at all time points assessed on PND 3
      (P<0.05), however, by PND 5 this response was attenuated showing a significant
      elevation only at 4-h post-injection. In these same pups, glucose levels were
      significantly reduced by 8-h post-injection on PND 3 and remained significantly
      lower until 8-h post-injection on PND 5 (P<0.05). Finally, the dams of endotoxin
      challenged pups, exhibited significantly less arched back nursing (P<0.05) but
      increased levels of off-nest time across the challenge period (P<0.05). These
      findings demonstrate that postnatal endotoxin exposure impacts on both endocrine
      and metabolic activity and that alterations in these two systems may in part be
      mediated by the impact of endotoxin exposure on maternal behaviour.

PMID- 15581673
TI  - Ovarian hormone withdrawal-induced "depression" in female rats.
AB  - Approximately 15% of child-bearing women develop postpartum depression (PPD), and
      many women with PPD experience anxious symptoms. It has been proposed that PPD is
      precipitated by the dramatic decline in reproductive hormones that occurs just
      after childbirth. To examine this hypothesis, ovariectomized female Sprague
      Dawley rats underwent a hormone-simulated pregnancy (HSP) regimen; during the
      subsequent hormone withdrawal period, rats were tested in the forced swim test or
      elevated plus-maze, animal models of depression and anxiety, respectively. The
      HSP regimen consisted of injections with progesterone and escalating doses of
      estradiol benzoate for 22 days; control rats received daily vehicle injections.
      One, two, four or seven days after the last hormone injection, separate groups of
      rats were tested once on either the forced swim test or the elevated plus-maze.
      To examine any hormone withdrawal-induced changes in activity levels, spontaneous
      locomotor activity was measured at the same time points. At 2 and 4 days after
      the last hormone injection, HSP-treated females displayed significant increases
      in immobility relative to vehicle-treated females in the forced swim test.
      Behavior on the elevated plus-maze did not differ between the HSP and control
      groups at any of the withdrawal time points. There were also no differences in
      spontaneous locomotor activity between the HSP and control females at any of the
      withdrawal time points. The results of this study suggest that postpartum hormone
      withdrawal may contribute to depressive symptoms experienced after giving birth,
      and that the HSP-hormone withdrawal protocol may provide a useful animal model of
      PPD.

PMID- 15581675
TI  - An inexpensive food cup for use in a commercially available food monitoring
      system.
AB  - The microstructure of feeding in rats can be probed using a variety of protocols
      that employ videotape-based ratings, pellet feeders, and/or laboratory balances.
      A recent commercial product (BioDAQ, Research Diets, New Brunswick, NJ) uses a
      metal food hopper placed on a load cell to monitor daily food pellet consumption.
      In this system, movements of the hopper during eating and the cessation of hopper
      movements after eating are combined with momentary hopper weights for subsequent
      analyses of daily meal patterns. Our laboratory has devised an improved food cup
      for the BioDAQ system that is easily balanced, minimizes spillage, and is
      compatible with either powdered chow diets or nonpelleted soft diets (e.g., a
      high-fat diet). In the present paper, we describe the methods used to fabricate
      this food cup and present data illustrating its use in meal pattern analyses for
      rats fed either a ground laboratory chow or a 33% high-fat diet.

PMID- 15581674
TI  - Opioid-mediated pain sensitivity in mice bred for high voluntary wheel running.
AB  - We tested the hypothesis that thermal tail-flick latency, a common measure of
      pain sensitivity in rodents, would be altered in lines of mice that had been
      selectively bred for high voluntary wheel-running behavior. Specifically, we
      predicted that the selected (High-Runner) lines would show decreased pain
      sensitivity relative to their control (C; randombred) lines, and would respond
      differently to drugs that block opioid receptors. We first compared tail-flick
      latency between High-Runner and C female mice during the day (no wheel access)
      and at night (with wheel access). Second, we compared effects of the opioid
      antagonist naloxone (10 mg/kg, i.p.) on tail-flick latency during the day (no
      wheel access). Third, we compared effects of naloxone (5 and 10 mg/kg, i.p.) and
      naltrexone, a longer-lasting opioid antagonist (0.1, 1, 5, 10, 50, and 100 mg/kg,
      i.p.), on voluntary wheel running. Tail-flick latencies were longer at night
      (when mice were active on wheels), but mice from High-Runner and C lines did not
      differ during the day or night. Administration of naloxone (10 mg/kg, i.p.)
      decreased tail-flick latency measured during the day, equally in High-Runner and
      C mice. Naloxone (5 and 10 mg/kg, i.p.) and high doses of naltrexone (50 and 100
      mg/kg, i.p.) decreased wheel running equally in High-Runner and C mice. Further
      studies will be required to determine whether other types of pain sensitivity
      have also failed to evolve in association with increased voluntary wheel running.

PMID- 15581676
TI  - Age- and sex-related disturbance in a battery of sensorimotor and cognitive tasks
      in Kunming mice.
AB  - A battery of tasks, i.e. beam walking, open field, tightrope, radial six-arm
      water maze (RAWM), novel-object recognition and olfactory discrimination, was
      used to determine whether there was age- and sex-related memory deterioration in
      Kunming (KM) mice, and whether these tasks are independent or correlated with
      each other. Two age groups of KM mice were used: a younger group (7-8 months old,
      12 males and 11 females) and an older group (17-18 months old, 12 males and 12
      females). The results showed that the spatial learning ability and memory in the
      RAWM were lower in older female KM mice relative to younger female mice and older
      male mice. Consistent with this, in the novel-object recognition task, a non
      spatial cognitive task, older female mice but not older male mice had impairment
      of short-term memory. In olfactory discrimination, another non-spatial task, the
      older mice retained this ability. Interestingly, female mice performed better
      than males, especially in the younger group. The older females exhibited
      sensorimotor impairment in the tightrope task and low locomotor activity in the
      open-field task. Moreover, older mice spent a longer time in the peripheral
      squares of the open-field than younger ones. The non-spatial cognitive
      performance in the novel-object recognition and olfactory discrimination tasks
      was related to performance in the open-field, whereas the spatial cognitive
      performance in the RAWM was not related to performance in any of the three
      sensorimotor tasks. These results suggest that disturbance of spatial learning
      and memory, as well as selective impairment of non-spatial learning and memory,
      existed in older female KM mice.

PMID- 15581677
TI  - Molecular diversity and accelerated evolution of C-type lectin-like proteins from
      snake venom.
AB  - A number of C-type lectin-like proteins that affect thrombosis and hemostasis by
      inhibiting or activating specific platelet membrane receptors or blood
      coagulation factors have been isolated from the venom of various snake species
      and characterized and more than 80 have been sequenced. Recent data on the
      primary sequences and 3D structures of C-type lectins and C-type lectin-like
      proteins from snake venoms have enabled us to analyze their molecular evolution.
      Statistical analysis of their cDNA sequences shows that C-type lectin-like
      proteins, with some exceptions, have evolved in an accelerated manner to acquire
      their diverse functions. Phylogenetic analysis shows that the A and B chains of C
      type lectin-like proteins are clearly separated from C-type lectins and that the
      A and B chains are further divided into a group of platelet receptor-binding
      proteins and a group of coagulation factor-binding proteins. Elucidation of the
      tertiary structures of several C-type lectin-like proteins led to the discovery
      of a unique domain-swapping interaction between heterodimeric subunits, which
      creates a concave surface for ligand binding.

PMID- 15581678
TI  - Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N
      type calcium channel blocker, in the formalin test in conscious rats.
AB  - The present study was undertaken to elucidate the antinociceptive effect of
      intrathecal administration of huwentoxin-I (HWTX-I), a N-type calcium channel
      blocker from the venom of the Chinese bird spider Ornithoctonus huwena (Wang)
      [=Selenocosmia huwena wang], by comparison with omega-Conotoxin-MVIIA (omega-CTX
      MVIIA) and morphine hydrochloride in the formalin test in conscious rats. Similar
      to omega-CTX-MVIIA and morphine, intrathecal pre-treatment with HWTX-I resulted
      in suppression of nociceptive behavior in a dose-dependent manner. The ED50
      values of HWTX-I and omega-CTX-MVIIA were 0.28 and 0.19 microg/kg, respectively.
      It was also found that, at lower doses (0.1 and 0.5 microg/kg), the
      antinociceptive effect of HWTX-I was identical to that of omega-CTX-MVIIA, while
      omega-CTX-MVIIA acted more remarkably than HWTX-I at higher dose (1.0 microg/kg).
      However, the antinociception induced by omega-CTX-MVIIA were companied with motor
      dysfunction, and these side-effects became more evident with the doses of omega
      CTX-MVIIA increasing. In contrast, HWTX-I did not show these side-effects at the
      doses of 0.5-1.0 microg/kg. Compared with HWTX-I and omega-CTX-MVIIA, the
      analgesic effect of intrathecal morphine hydrochloride was initiated faster, but
      lasted for a shorter time (about 2-3 h at 1.0 microg/kg) than that of HWTX-I and
      omega-CTX-MVIIA (about 4- 5 h at 1.0 microg/kg). Therefore, the present results
      show that, like omega-CTX-MVIIA, the intrathecal administration of HWTX-I is
      effective in antinociception in the rat model of the formalin test.

PMID- 15581679
TI  - Purification and characterization of Taiwan cobra venom proteins with weak
      toxicity.
AB  - Two proteins G2a and G2b with molecular masses of approximately 24 kDa were
      isolated from Naja naja atra (Taiwan cobra) venom using sequential chromatography
      on gel filtration, ion-exchanger and reverse phase columns. The results of Edman
      degradation and mass analysis revealed that G2a is a cysteine-rich protein
      reported previously, and G2b is a novel polypeptide. CD spectra showed that the
      gross conformation of G2a and G2b notably differed. G2a exhibited an activity
      higher than that noted with G2b on inhibiting carbachol-induced muscle
      contraction. However, the two proteins weakly blocked muscle contraction evoked
      by K+. The observations that the two proteins exhibit the toxic activity in the
      concentration of micromolar range suggest that they are inherently weak toxins as
      other snake venom cysteine-rich proteins.

PMID- 15581680
TI  - Pediatric electrocardiograph abnormalities following Centruroides limpidus
      tecomanus scorpion envenomation.
AB  - Scorpionism is an endemic public health problem in Mexico [Hoffmann, C.C., 1936.
      La distribucion geografica de los alacranes peligrosos en la Republica Mexicana.
      Bol. Inst. Hygiene Mex. 2, 321; Hoffmann, C.C., Nieto, D.R., 1939. Segunda
      contribucion al conocimiento de los alacranes mexicanos. Anal. Inst. Biol. 10, 83
      92; Mazzoti, L., Bravo-Becherelle, M.A., 1963. Scorpionism in the Mexican
      Republic. In: Keegan, H.L., McFarlane, W.V. (Eds.), Venomous and Poissonous
      Animals and Noxious Plants of the Pacific Area. Pergamon Press, London, pp. 119
      131; Monroy-Velasco, J., 1961. Alacranes venenosos de Mexico. Rev. Mex. Cien.
      Med. Biol., Mex. 1, 1-23; Diaz-Najera, A., 1975. Listas y datos de distribucion
      geografica de los alacranes de Mexico. Rev. Inv. Salud. Publica. (Mex.) 35, 1;
      Velasco-Castrejon, O., Lara-Aguilera, R., Alatorre, H., 1976. Aspectos
      epidemiologicos y clinicos de la picadura de alacran en una area hiperendemica.
      Rev. Inv. Salud Publica. (Mex.) 36, 93-103; Dehesa-Davila, M., Possani, L.D.,
      1994. Scorpionism and serotherapy in Mexico. Toxicon 32 (9), 1015-1018]. In this
      prospective study, we assess cardiovascular disorders in children via
      electrocardiographic (ECG) recordings following envenomation by scorpion species
      Centruroides limpidus tecomanus found in the state of Colima, Mexico. We analyzed
      113 cases between the ages of 5 and 14 years. Among the most frequent symptoms
      presented included local pain (99.1%) and paresthesia (75.2%), pruritus (36.3%),
      sialorrhoea (35.4%), and nystagmus (24.8%). Cardiovascular disorders were
      observed in 39.8% of cases, 71% of which were rhythm abnormalities. We find a
      significant association between the frequency of ECG alterations and age, whereby
      8-9-year-old children are more likely to experience ECG alterations when compared
      with other tested age groups.

PMID- 15581681
TI  - Isolation and molecular cloning of novel peptide toxins from the sea anemone
      Antheopsis maculata.
AB  - Three peptide toxins (Am I-III) with crab toxicity were isolated from the sea
      anemone Anthopleura maculata by gel filtration and reverse-phase HPLC. Am I was
      weakly lethal to crabs (LD50 830 microg/kg) and Am III was potently lethal (LD50
      70 microg/kg), while Am II was only paralytic (ED50 420 microg/kg). The complete
      amino acid sequences of the three toxins were determined by cDNA cloning based on
      3'-Race and 5'-Race. Although Am III (47 residues) is an analogue of the well
      known type 1 sea anemone sodium channel toxins, both Am I (27 residues) and II
      (46 residues) are structurally novel peptide toxins. Am I is a new toxin having
      no sequence homologies with any toxins. Am II shares 28-39% identity with the
      recently characterized sea anemone toxins inhibiting specialized ion channels,
      BDS-I and II from Anemonia sulcata and APETx1 and 2 from Anthopleura
      elegantissima. The precursor proteins of the three toxins are commonly composed
      of a signal peptide, a propart with a pair of basic residues (Lys-Arg) at the end
      and the remaining portion. Very interestingly, the Am I precursor protein
      contains as many as six copies of Am I.

PMID- 15581682
TI  - Monoamine oxidase inhibitory activities of the scorpion Mesobuthus gibbosus
      (Buthidae) venom peptides.
AB  - In the present study, crude venom of Mesobuthus gibbosus (Buthidae), a scorpion
      distributed all over Anatolia was isolated and purified by the Sephadex G-50 gel
      filtration and high pressure liquid chromatographic (HPLC) separation. Two of the
      five fractions (fractions 4 and 5) obtained from the Sephadex G-50 filtration and
      detected as lethal on mice and Musca domestica larvae in in vivo toxicity tests,
      were independently subjected to the HPLC separation. Only one of seven fractions
      (fraction 5.5*) obtained from the HPLC separation of the fraction 5 was found to
      be extremely lethal. Sodium dodecylsulfate polyacrylamide gel electrophoretic
      (SDS-PAGE) analysis of the crude venom and its chromatographic fractions
      demonstrated that crude venom consisted of peptides with molecular weights of
      6500-210,000 Da. The neurotoxic fraction 5.5* appeared as a single band of 28,000
      Da and two bands of 6200 and 22,000 Da in SDS-PAGE under non-reducing and
      reducing conditions, respectively, suggesting that it might consist of two chains
      attached by a disulfide bridge. Fractions 5 and 5.5* inhibited monoamine oxidase
      A (MAO-A) of rat liver reversibly and non-competitively, in a concentration
      dependent manner. Fraction 5.5* appeared as a potent and specific MAO-A inhibitor
      with a Ki value of 0.12 mg venom proteinml(-1). The inhibitory effect of venom
      peptide 5.5* on MAO-A was found to be dependent on the preincubation time
      suggesting that the peptide binds to some site other than the substrate-binding
      site. Results of the present study demonstrated that M. gibbosus venom contains a
      peptide with specific MAO-A inhibitory activity which may be responsible for the
      anxiogenic effects of the scorpion venoms on animals and humans.

PMID- 15581683
TI  - The long-term effect of toosendanin on current through nifedipine-sensitive Ca2+
      channels in NG108-15 cells.
AB  - Toosendanin is a triterpenoid derivative extracted from Melia toosendan Sieb et
      Zucc. Previous studies demonstrated that toosendanin could block
      neurotransmission and stimulate PC12 cell into differentiation and apoptosis.
      These actions of toosendanin were suggested to result from a continuous increase
      in Ca2+ influx, which led to intracellular Ca2+ overload. Here, we observed the
      long-term effect of toosendanin on Ca2+ channels in NG108-15 cells by whole-cell
      patch-clamp recording. Obtained data showed that a prolonged exposure to
      toosendanin induced a continuous increase in the Ca2+ influx in a concentration
      and time-dependent manner while a brief treatment induced an irreversible
      increase in Ca2+ influx in differentiated NG108-15 cells. The nifedipine
      sensitive L-type currents were significantly increased after exposure to TSN
      while the nifedipine-resistant or omega-conotoxin MVIIC-sensitive currents were
      not affected.

PMID- 15581684
TI  - Polyhydroxylated amide analogs of yessotoxin from Protoceratium reticulatum.
AB  - Two analogs of yessotoxin were isolated from extracts of a culture of
      Protoceratium reticulatum. The structures of the analogs were identified as
      trihydroxylated amides of 41a-homoyessotoxin (1) and 9-methyl-41a-homoyessotoxin
      (2) by one- and two-dimensional 1H and 13C NMR spectroscopy and LC-MS3 analyses.
      Structures were further confirmed by micro-scale chemical conversions combined
      with LC-MS3 analyses. No toxic effects were recorded in mice injected
      intraperitoneally with 2 at a dose of 5000 microg/kg.

PMID- 15581685
TI  - Further report of the occurrence of tetrodotoxin and new analogues in the Anuran
      family Brachycephalidae.
AB  - Tetrodotoxin (TTX) is one of the most potent toxin already isolated, which occurs
      in a wide range of marine as well as terrestrial animals such as in newts and
      anurans. In this work, the occurrence of TTX and analogues was examined in three
      brachycephalid species: Brachycephalus ephippium, B. nodoterga and B. pernix
      using LC-FLD and LC-MS/MS. In toxicity assay (intra-peritonial injection in mice)
      B. nodoterga extracts were non-toxic, while B. pernix extract exhibit the highest
      toxicity among the studied species. Skin showed the highest toxic, followed by
      the liver. Retention time data in the LC-FLD system indicated the presence of
      TTX, 4-epiTTX, 4,9-anhydroTTX and TDA, SIM data confirmed the presence of these
      compounds and revealed other analogs such as 11-norTTX-6(S)-ol, 5-deoxyTTX, 11
      deoxyTTX, 11-oxoTTX, 6-epiTTX. Two new components were also identified by mass
      spectrometry (348 and 330Da). These unknown compounds have daughter ions similar
      to TTX, suggesting new putative TTX analogues.

PMID- 15581686
TI  - Microarray analysis of gene expression in chondrosarcoma cells treated with bee
      venom.
AB  - Bee venom (BV) has a broad array of clinical applications in Korean medicine,
      including treatment of inflammatory conditions such as arthritis. The final
      common pathway of many arthropathies is the destruction of articular cartilage
      and consequent loss of articular function. Chondrocyte dysfunction plays a key
      role in the pathogenesis of such disorders. To explore the global gene expression
      profiles in a human chondrocyte-like cell line treated with BV, microarray
      analysis was performed. The HTB-94 human chondrosarcoma cells were treated with
      BV, lipopolysaccharide (LPS), or both. Of the 344 genes profiled in this study,
      with a cut-off level of 4-fold change in the expression, (1) 35 were
      downregulated following BV treatment, (2) 16 were upregulated and 7 downregulated
      following LPS treatment, and (3) 32 were downregulated following co-stimulation
      of BV and LPS. The results of the present study shows that treatment of BV
      reversed the LPS-induced upregulation of such genes as interleukin-6 (IL-6)
      receptor, matrix metalloproteinase 15 (MMP-15), tumor necrosis factor (ligand)
      superfamily-10, caspase-6 and tissue inhibitor of metalloproteinase-1 (TIMP-1).
      It is thought that microarrays will play an ever-growing role in the advance of
      our understanding of the pharmacologic actions of BV in the treatment of
      arthritis.

PMID- 15581687
TI  - Weak neurotoxin from Naja kaouthia cobra venom affects haemodynamic regulation by
      acting on acetylcholine receptors.
AB  - Recent in vitro studies of weak neurotoxins from snake venoms have demonstrated
      their ability to interact with both muscle-type and neuronal alpha7 nicotinic
      acetylcholine receptors (nAChR). However, the biological activity in vivo of weak
      neurotoxins remains largely unknown. We have studied the influence of weak
      neurotoxin (WTX) from the venom of cobra Naja kaouthia on arterial blood pressure
      (BP) and heart rate (HR) in rats and mice. It was found that intravenous
      injection of WTX induced a dose-dependent decrease in BP and an increase in HR in
      both species, the rats being more sensitive to WTX. Application of WTX following
      blockade of nAChRs or muscarinic acetylcholine receptors (mAChR) by hexamethonium
      or atropine, respectively, showed that both nAChRs and mAChRs are involved in the
      haemodynamic effects of WTX. Blockade of either nAChRs or mAChRs affected WTX
      action differently in rats and mice, thus reflecting interspecies differences in
      haemodynamic regulation.

PMID- 15581688
TI  - Structural and biological characterization of three novel mastoparan peptides
      from the venom of the neotropical social wasp Protopolybia exigua (Saussure).
AB  - The venom of the Neotropical social wasp Protopolybia exigua(Saussure) was
      fractionated by RP-HPLC resulting in the elution of 20 fractions. The homogeneity
      of the preparations were checked out by using ESI-MS analysis and the fractions
      15, 17 and 19 (eluted at the most hydrophobic conditions) were enough pure to be
      sequenced by Edman degradation chemistry, resulting in the following sequences:
      Protopolybia MPI I-N-W-L-K-L-G-K-K-V-S-A-I-L-NH2 Protopolybia-MP II I-N-W-K-A-I-I
      E-A-A-K-Q-A-L-NH2 Protopolybia-MP III I-N-W-L-K-L-G-K-A-V-I-D-A-L-NH2 All the
      peptides were manually synthesized on-solid phase and functionally characterized.
      Protopolybia-MP I is a hemolytic mastoparan, probably acting on mast cells by
      assembling in plasma membrane, resulting in pore formation; meanwhile, the
      peptides Protopolybia-MP II and -MP III were characterized as a non-hemolytic
      mast cell degranulator toxins, which apparently act by virtue of their binding to
      G-protein receptor, activating the mast cell degranulation.

PMID- 15581689
TI  - Toxicity and mAChRs binding activity of Cassiopea xamachana venom from Puerto
      Rican coasts.
AB  - A separation of toxic components from the upside down jellyfish Cassiopea
      xamachana (Cx) was carried out to study their cytotoxic effects and examine
      whether these effects are combined with a binding activity to cell membrane
      receptors. Nematocysts containing toxins were isolated from the autolysed
      tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from
      the pellets by ultracentrifugation. For identifying its bioactive components,
      CxTX was fractionated by gel filtration chromatography into six fractions (named
      fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however,
      the hemolytic activity was tested on saline washed human erythrocytes. The LD50
      of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were
      0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal
      at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2)
      activities of most fractions were well correlated with their mice toxicity.
      However, fraction VI, which contains the low molecular mass protein components (<
      or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest
      hemolytic activity, and bound significantly to the acetylcholine muscarinic
      receptors (mAChRs) isolated from rat brain. The results suggested that fraction
      VI contains proteinaceous components contributing to most of cytolysis as well as
      membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may
      contribute to the venom lethality and paralytic effects.

PMID- 15581690
TI  - Mass spectrometric and high performance liquid chromatography profiling of the
      venom of the Brazilian vermivorous mollusk Conus regius: feeding behavior and
      identification of one novel conotoxin.
AB  - Carnivorous mollusks belonging to the genus Conus paralyze their prey by
      injecting a rich mixture of biologically active peptides. Conus regius is a
      vermivorous member of this genus that inhabits Brazilian tropical waters. Inter-,
      intra-species and individual variations of cone snail venom have been previously
      reported. In order to investigate intra-specific differences in C. regius venom,
      its feeding behavior and the correlation between these two factors, animals were
      pooled according to gender, size and season of collection, and their venom
      composition was compared by high performance liquid chromatography (HPLC). Both
      the whole venom and one specific peak were monitored by HPLC. Chromatographic
      profiles revealed no significant differences in their peak areas, indicating that
      the venom composition, based solely in the presence or absence of the major
      peaks, is stable regardless of season, gender and size. Therefore, analysis of
      one given toxin, eluting in one of the major peaks, is representative among the
      population. Moreover, this work presents the identification of one novel
      conotoxin (rg11a), which amino acid sequence was deduced by mass spectrometry.

PMID- 15581691
TI  - Anticomplementary activity of equine whole IgG antivenoms: comparison of three
      fractionation protocols.
AB  - Early adverse reactions occur in a number of patients treated with heterologous
      antivenoms and have been associated with anticomplementary activity (ACA). In
      order to reduce the ACA of equine whole IgG antivenoms produced by caprylic acid
      fractionation, three different fractionation protocols were compared: (a) routine
      caprylic acid fractionation; (b) caprylic acid fractionation followed by beta
      propiolactone treatment; and (c) caprylic acid fractionation followed by ion
      exchange chromatography using a quaternary ammonium membrane. The three protocols
      yielded products with similar physicochemical characteristics and anti-Bothrops
      asper venom antibody titers, except that ion-exchange purified antivenom had a
      lower protein concentration. Antivenoms fractionated by using beta-propiolactone
      or filtration through quaternary ammonium membrane had a significantly reduced in
      vitro ACA. A preparation of caprylic acid-fractionated antivenom was heated in
      order to induce the formation of protein aggregates; however, its ACA was similar
      to non-heated antivenom. None of the antivenoms affected the hemolytic activity
      of serum complement in rabbits after a bolus intravenous administration. It is
      concluded that (a) beta-propiolactone and quaternary ammonium membranes
      significantly reduce in vitro ACA of caprylic acid-fractionated equine antivenom,
      and (b) the validity of in vitro ACA as a predictor of EAR needs to be reexamined
      in clinical and experimental studies, since it may not adequately predict in vivo
      complement activation by antivenoms.

PMID- 15581692
TI  - Development, dynamics and pathology of neuronal networks: from molecules to
      functional circuits. Proceedings of the 23rd International Summer School of Brain
      Research. August 25-29, 2003. Amsterdam, The Netherlands.

PMID- 15581693
TI  - Neuronal network formation in human cerebral cortex.
AB  - Knowledge of the development of structural and functional connectivity in the
      human brain is of great fundamental and practical importance, but is largely
      lacking. In this review qualitative and quantitative data are presented on the
      formation of dendrites, axons and synapses in different regions of the human
      cerebral cortex from prenatal life until adulthood. This information is compiled
      to provide baseline information for comparison of similar data derived from
      postmortem brains of persons with developmental brain disorders. In addition,
      some data are provided on the influence of the sensory environment on cortical
      network formation in animals.

PMID- 15581694
TI  - Regulation of dendritic growth by calcium and neurotrophin signaling.
AB  - The development of cortical dendrites is regulated by both activity-dependent and
      activity-independent signaling. Activity-dependent dendritic growth involves
      calcium-dependent gene expression. Both CREB and CREST are transactivators that
      contribute to calcium-dependent dendritic growth. Dendritic development is also
      regulated by extracellular factors such as neurotrophins. Neurotrophin-dependent
      dendritic growth is mediated by the MAP kinase and PI 3-kinase pathways.
      Selective responsiveness to activity cues and neurotrophins may contribute to
      morphological diversity in the nervous system.

PMID- 15581695
TI  - Dynamics and pathology of dendritic spines.
AB  - Dendritic spines are key players in information processing in the brain. Changes
      in spine shape and wholesale spine turnover provide mechanisms for modifying
      existing synaptic connections and altering neuronal connectivity. Although
      neuronal cell death in acute and chronic neurodegenerative diseases is clearly an
      important factor in decline of cognitive or motor function, loss of dendritic
      spines, in the absence of cell death, may also contribute to impaired brain
      function in these diseases, as well as in psychiatric disorders and aging.
      Because spines can function in neuroprotection in vitro, advances toward a
      molecular understanding of spine maintenance might one day aid in the design of
      therapies to minimize neurological damage following excitotoxic injury. In
      addition, progress in defining the biochemical basis of spine development and
      stabilization may yield insights into mental retardation and psychiatric
      disorders.

PMID- 15581696
TI  - Introduction to the sixteenth C.U. Ariens Kappers lecture.

PMID- 15581697
TI  - Mechanisms of retinotopic map development: Ephs, ephrins, and spontaneous
      correlated retinal activity.
AB  - This chapter summarizes mechanisms that control the development of retinotopic
      maps in the brain, focusing on work from our laboratory using as models the
      projection of retinal ganglion cells (RGCs) to the chick optic tectum (OT) or
      rodent superior colliculus (SC). The formation of a retinotopic map involves the
      establishment of an initial, very coarse map that subsequently undergoes large
      scale remodeling to generate a refined map. All arbors are formed by interstitial
      branches that form in a topographically biased manner along RGC axons that
      overshoot their correct termination zone (TZ) along the anterior-posterior (A-P)
      axis of the OT/SC. The interstitial branches exhibit directed growth along the
      lateral-medial (L-M) axis of the OT/SC to position the branch at the
      topographically correct location, where it arborizes to form the TZ. EphA
      receptors and ephrin-A ligands control in part RGC axon mapping along the A-P
      axis by inhibiting branching and arborization posterior to the correct TZ. Ephrin
      B1 acts bifunctionally through EphB forward signaling to direct branches along
      the L-M axis of the OT/SC to their topographically correct site. Computational
      modeling indicates that multiple graded activities are required along each axis
      to generate a retinotopic map, and makes several predictions, including: the
      progressive addition of ephrin-As within the OT/SC, due to its expression on RGC
      axon branches and arbors, is required to increase topographic specificity in
      branching and arborization as well as eliminate the initial axon overshoot, and
      that interactions amongst RGC axons that resemble correlated neural activity are
      required to drive retinotopic refinement. Analyses of mutant mice that lack early
      spontaneous retinal waves that correlate activity amongst neighboring RGCs,
      confirm this modeling prediction and show that correlated activity during an
      early brief critical period is required to drive the large-scale remodeling of
      the initially topographically coarse projection into a refined one. In summary,
      multiple graded guidance molecules, retinal waves and correlated spontaneous RGC
      activity cooperate to generate retinotopic maps.

PMID- 15581698
TI  - Biologically plausible models of neurite outgrowth.

PMID- 15581699
TI  - Competition in neurite outgrowth and the development of nerve connections.
AB  - During the development of the nervous system, neurons form their characteristic
      morphologies and become assembled into synaptically connected networks. In both
      neuronal morphogenesis and the development of nerve connections, competition
      plays an important role. Although the notion of competition is commonly used in
      neurobiology, there is little understanding of the nature of the competitive
      process and the underlying molecular and cellular mechanisms. In this chapter, we
      review a model of competition between outgrowing neurites, as well as various
      models of competition that have been proposed for the refinement of connections
      that takes place in the development of the neuromuscular and visual systems. We
      describe in detail a model that links competition in the development of nerve
      connections with the underlying actions and biochemistry of neurotrophic factors.

PMID- 15581700
TI  - Molecular substrates of plasticity in the developing visual cortex.
AB  - Ocular dominance plasticity may be the paradigmatic in vivo model of activity
      dependent plasticity. More than four decades of intense research has delineated
      the network-level rules that govern synaptic change in this model. The recent
      characterization of a murine model for ocular dominance plasticity has
      facilitated rapid progress on a new front, extending our understanding of the
      molecular mechanisms underlying ocular dominance plasticity. In this review, we
      highlight recent advances in this research effort, focusing in particular on
      signaling pathways mediating shifts in ocular dominance, and mechanisms
      underlying the timing of the critical period.

PMID- 15581701
TI  - Excitatory-inhibitory balance and critical period plasticity in developing visual
      cortex.

PMID- 15581702
TI  - Structural plasticity in the developing visual system.
AB  - The visual system has been used extensively to study cortical plasticity during
      development. Seminal experiments by Hubel and Wiesel (Wiesel, T.N. and Hubel,
      D.H. (1963) Single cell responses in striate cortex of kittens deprived of vision
      in one eye. J. Neurophysiol., 26: 1003-1017.) identified the visual cortex as a
      very attractive model for studying structural and functional plasticity regulated
      by experience. It was discovered that the thalamic projections to the visual
      cortex, and neuronal connectivity in the visual cortex itself, were organized in
      alternating columns dominated by input from the left or the right eye. This
      organization was shown to be strongly influenced by manipulating binocular input
      during a specific time point of postnatal development known as the critical
      period. Two chapters in this volume review the molecular and functional aspects
      of this form of plasticity. This chapter reviews the structural changes that
      occur during ocular dominance (OD) plasticity and their possible functional
      relevance, and discusses developments in the methods that allow the analysis of
      the molecular and cellular mechanisms that regulate them.

PMID- 15581703
TI  - Mechanisms controlling the formation of retinal mosaics.
AB  - Most regions of the nervous system derive their power of processing from a
      modular architecture. The retina is an outstanding example of modular circuit
      design. Retinal neurons are stacked in layers and within each layer neurons of
      the same type commonly form orderly arrays, or mosaics. Here we review current
      knowledge on the mechanisms of retinal mosaic formation, and discuss the
      hypothesis that retinal mosaics are the building blocks in the assembly of
      retinal circuitry.

PMID- 15581704
TI  - Laminar circuit formation in the vertebrate retina.
AB  - Neuronal function depends on the accurate wiring between pre- and postsynaptic
      cells. Determining the mechanisms underlying precision in neuronal connectivity
      is challenging because of the complexity of the nervous system. In diverse parts
      of the nervous system, regions of synaptic contact are organized into distinct
      parallel layers, or laminae, that are correlated with distinct functions. Such an
      arrangement enables the development of synapse specificity to be more readily
      investigated. Here, we present an overview of the developmental mechanisms that
      are thought to underlie the formation of synaptic layers in the vertebrate
      retina, a highly laminated CNS structure. We will contrast the roles of activity
      dependent and activity-independent mechanisms in establishing functionally
      discrete sublaminae in the inner retina, where circuits involving many subtypes
      of retinal neurons are assembled precisely. In addition, we will discuss new
      optical imaging approaches for elucidating how retinal synaptic lamination occurs
      in vivo.

PMID- 15581705
TI  - Dynamics and plasticity in developing neuronal networks in vitro.
AB  - When dissociated cortical tissue is brought into culture, neurons readily grow
      out by forming axonal and dendritic arborizations and synaptic connections. These
      developing neuronal networks in vitro display spontaneous firing activity from
      about the end of the first week in vitro. When cultured on multielectrode arrays
      firing activity can be recorded from many neurons simultaneously over long
      periods of time. These experimental approaches provide valuable data for studying
      firing dynamics in neuronal networks in relation to an ongoing development of
      neurons and synaptic connectivity in the network. This chapter summarizes recent
      findings on the characteristics and developmental changes in the spontaneous
      firing dynamics. These changes include long-lasting transient periods of
      increased firing at individual sites on a time scale of days to weeks, and an age
      specific repetitive pattern of synchronous network firing (network bursts) on a
      time scale of seconds. Especially the spatio-temporal organization of firing
      within network bursts showed great stability over many hours. In addition, a
      progressive day-to-day evolution was observed, with an initial broadening of the
      burst firing rate profile during the 3rd week in vitro (WIV) and a pattern of
      abrupt onset and precise spike timing from the 5th WIV onwards. These
      developmental changes are discussed in the light of structural changes in the
      network and activity-dependent plasticity mechanisms. Preliminary findings are
      presented on the pattern of spike sequences within network burst, as well as the
      effect of external stimulation on the spatio-temporal organization within network
      bursts.

PMID- 15581706
TI  - Learning in ex-vivo developing networks of cortical neurons.
AB  - This contribution describes the use of multi-site interaction with large cortical
      networks in the study of learning. The general physiological properties of the
      network are described, and the concept of learning is mapped to the experimental
      network preparation. Learning is then analyzed in terms of exploration (defined
      as changes in the configuration of associations within the biological network)
      and recognition (the stabilization of "worthy" associations).

PMID- 15581707
TI  - Role of synaptic inhibition in spatiotemporal patterning of cortical activity.
AB  - Developmental upregulation of the GABAA receptor alpha1 subunit causes a faster
      decay of GABAergic inhibitory postsynaptic currents (IPSCs) in the visual cortex
      around the time of eye opening. In alpha1 deficient mice, a juvenile type of
      GABAA receptors is retained during maturation. As a result the decay time of the
      IPSCs is longer in alpha1-/- mice than in WT mice during the whole life span of
      the mice. Hence they form a valuable mouse model for studies on cellular aspects
      of neuronal network functioning. Using voltage sensitive dye imaging methods, we
      monitored the spatiotemporal excitation patterning in visual cortex slices upon
      local stimulation of the network. We found that in the alpha1-/- mice, the
      ability of the network to fire synchronously at gamma-frequencies (20-50 Hz) is
      diminished. This finding indicates that early onset of GABA synapse maturation is
      required for the normal neuronal network function in the maturating visual
      cortex.

PMID- 15581708
TI  - Synaptic mechanisms that shape visual signaling at the inner retina.
AB  - The retina is a layered structure that processes information in two stages. The
      outer plexiform layer (OPL) comprises the first stage and is where
      photoreceptors, bipolar cells, and horizontal cells interact synaptically. This
      is the synaptic layer where ON and OFF responses to light are formed, as well as
      the site where receptive field center and surround organization is first thought
      to occur. The inner plexiform layer (IPL) is where the second stage of synaptic
      interactions occurs. This synaptic layer is where subsequent visual processing
      occurs that may contribute to the formation of transient responses, which may
      underlie motion and direction sensitivity. In addition, synaptic interactions in
      the IPL may also contribute to the classical ganglion cell receptive field
      properties. This chapter will focus on the synapse and network properties at the
      IPL that sculpt light-evoked ganglion cell responses. These include synaptic
      mechanisms that may shape ganglion cell responses like desensitizing glutamate
      receptors and transporters, which remove glutamate from the synapse. Recent work
      suggests that inhibitory signaling at the IPL contributes to the surround
      receptive field organization of ganglion cells. A component of this amacrine cell
      inhibitory signaling is mediated by GABAC receptors, which are found on bipolar
      cell axon terminals in the IPL. Pharmacological experiments show that a component
      of the ganglion cell surround signal is mediated by these receptors, indicating
      that the ganglion cell center and surround receptive field organization is not
      formed entirely in the outer plexiform layer, as earlier thought.

PMID- 15581709
TI  - The involvement of glutamate-gated channels in negative feedback from horizontal
      cells to cones.
AB  - Photoreceptors are the light sensitive cells in the retina. They project to
      horizontal cells and bipolar cells via a glutamatergic feed forward pathway.
      Horizontal cells are strongly electrically coupled and integrate in that way the
      input from the photoreceptors. Horizontal cells feedback to cones negatively. The
      combined signal from the photoreceptors and the horizontal cells is sent to the
      bipolar cells. The feedback pathway from horizontal cells to cones is thought to
      form the basis for the center/surround organization of bipolar cells. The nature
      of the feedback pathway is an issue of intense debate. It was thought for a long
      time that this feedback pathway was GABAergic, because cones have GABA-receptors
      and horizontal cells release GABA via a GABA-transporter working in the reversed
      direction. However, recently we showed in goldfish that horizontal cells feed
      back to cones via an alternative mechanism. In goldfish, negative feedback from
      horizontal cells to cones shifts the calcium current of the cone to more negative
      potentials. This feedback pathway is independent of GABA, since feedback cannot
      be blocked by either saturating concentrations of PTX, the GABA-transporter
      blocker SKF89976A, or application of GABA. The mechanism of negative feedback
      from horizontal cells to cones involves hemichannels located at the tips of the
      invaginating horizontal cells, just opposite to the calcium channels of the
      cones. Current flowing through these hemichannels changes the extracellular
      potential deep in the synaptic cleft and in that way modulates the calcium
      current of the cones. Such a modulation of the extracellular potential is called
      ephaptic. If negative feedback from horizontal cells to cones is indeed ephaptic,
      other channels present in the synapse should also be able to act as a current
      source, i.e., should also be able to change the output of the cone. We showed
      that glutamate-gated channels present at the tips of the horizontal cell
      dendrites can also mediate feedback responses. Surprisingly, although the
      glutamate-gated conductance of the horizontal cells is eight times the
      hemichannel conductance, glutamate-gated channels are not the major current
      source in negative feedback from horizontal cells to cones. In this chapter we
      present evidence that this is due to the more focal localization of the
      hemichannels, compared to a diffuse and extrasynaptic localization of the
      glutamate-gated channels.

PMID- 15581710
TI  - Compensatory physiological responses to chronic blockade of amino acid receptors
      during early development in spontaneously active organotypic cerebral cortex
      explants cultured in vitro.
AB  - Paired organotypic explants from rat occipital cortex were cultured for up to
      three weeks in the presence of selective blockers of amino acid receptor
      blockers, during which period spontaneous action potential generation was
      monitored electrophysiologically. In contrast to isolated explants (Corner, M.A.,
      van Pelt, J., Wolters, P.S., Baker, R.E.and Nuytinck, R.H. (2002) Physiological
      e.ects of sustained blockade of excitatory synaptic transmission on spontaneously
      active developing neuronal networks--an inquiry into the reciprocal linkage
      between intrinsic biorhythms and neuroplasticity in early ontogeny. Neurosci.
      Biobehav. Rev., 26: 127-185), which upregulated their initially depressed
      spontaneous bursting activity only under conditions of N-methyl D-aspartate
      (NMDA) receptor blockade, cross-innervated co-cultures showed a large degree of
      functional recovery even when combined NMDA and AMPA receptor blockade was
      carried out. This compensatory activity could be eliminated by acute addition of
      a selective kainate receptor blocker to the medium. When kainate along with AMPA
      and NMDA receptor mediated activity was chronically suppressed, however,
      considerable functional recovery--in the form of recurrent burst discharges--took
      place gradually over a period of three weeks in vitro. These spontaneous bursts
      disappeared rapidly upon treatment with the muscarinic receptor blocker,
      atropine, but continuous low-level firing emerged at the same time. Similar
      "tonic" background activity was induced in control cultures as well, but without
      any noticeable reduction in burst discharges. Co-cultured neocortex explants, in
      which cyto-morphological maturation proceeds to a far greater degree than in
      isolated explants (Baker, R.E.and van Pelt, J. (1997) Co-cultured but not
      isolated cortical explants display normal dendritic development: a longterm
      quantitative study. Dev. Brain Res., 98: 21-27) are evidently capable of an
      astonishing degree of functional compensation for loss of excitatory synaptic
      drive during development. It could be shown, furthermore, that such homeostatic
      responses are not mediated largely by a weakening of inhibitory mechanisms in the
      absence of spontaneous firing. Chronic inhibitory synaptic blockade, on the other
      hand, led to intensified bursting activity which gradually normalized over a 3
      week culture period. The cellular basis for this reversal of the disinhibited
      state, as well as for the residual neuronal firing even after cholinergic
      mechanisms have been largely eliminated, is at present unknown. The degree to
      which immature cortical networks attempt to compensate for altered levels of
      physiological activity, as documented in the present report, is another
      indication of how important such activity can be for normal development (see
      Corner, M.A., van Pelt, J., Wolters, P.S., Baker, R.E. and Nuytinck, R.H. (2002)
      Physiological e.ects of sustained blockade of excitatory synaptic transmission on
      spontaneously active developing neuronal networks-an inquiry into the reciprocal
      linkage between intrinsic biorhythms and neuroplasticity in early ontogeny.
      Neurosci. Biobehav. Rev., 26: 127-185).. At the same time, the large variations
      in overall firing levels and "macro-scale" temporal patterns from culture to
      culture within a given series, despite all attempts at identical preparation of
      the explants, can only mean that the "set-points" for such regulation are
      themselves subject to unknown ontogenetic factors which, apparently, are
      nonuniformly distributed even within a restricted region of the neocortex. On the
      other hand, it was striking to note that, regardless of age or treatment, an
      unexpected degree of consistency in temporal patterning existed at "mini-" and
      "micro-" time-scales (viz., EEG delta and beta frequency ranges, respectively)
      even when network bursting tendencies became greatly reduced in favor of tonic
      firing.

PMID- 15581711
TI  - A visual salience map in the primate frontal eye field.
AB  - Models of attention and saccade target selection propose that within the brain
      there is a topographic map of visual salience that combines bottom-up and top
      down influences to identify locations for further processing. The results of a
      series of experiments with monkeys performing visual search tasks have identified
      a population of frontal eye field (FEF) visually responsive neurons that exhibit
      all of the characteristics of a visual salience map. The activity of these FEF
      neurons is not sensitive to specific features of visual stimuli; but instead,
      their activity evolves over time to select the target of the search array. This
      selective activation reflects both the bottom-up intrinsic conspicuousness of the
      stimuli and the top-down knowledge and goals of the viewer. The peak response
      within FEF specifies the target for the overt gaze shift. However, the selective
      activity in FEF is not in itself a motor command because the magnitude of
      activation reflects the relative behavioral significance of the different stimuli
      in the visual scene and occurs even when no saccade is made. Identifying a visual
      salience map in FEF validates the theoretical concept of a salience map in many
      models of attention. In addition, it strengthens the emerging view that FEF is
      not only involved in producing overt gaze shifts, but is also important for
      directing covert spatial attention.

PMID- 15581712
TI  - Chronic multiunit recordings in behaving animals: advantages and limitations.
AB  - By simultaneous recording from neural responses at many different loci at the
      same time, we can understand the interaction between neurons, and thereby gain
      insight into the network properties of neural processing, instead of the
      functioning of individual neurons. Here we will discuss a method for recording in
      behaving animals that uses chronically implanted micro-electrodes that allow one
      to track neural responses over a long period of time. In a majority of cases,
      multiunit activity, which is the aggregate spiking activity of a number of
      neurons in the vicinity of an electrode tip, is recorded through these
      electrodes, and occasionally single neurons can be isolated. Here we compare the
      properties of multiunit responses to the responses of single neurons in the
      primary visual cortex. We also discuss the advantages and disadvantages of the
      multiunit signal as opposed to a signal of single neurons. We demonstrate that
      multiunit recording provides a reliable and useful technique in cases where the
      neurons at the electrodes have similar response properties. Multiunit recording
      is therefore especially valuable when task variables have an effect that is
      consistent across the population of neurons. In the primary visual cortex, this
      is the case for figure-ground segregation and visual attention. Multiunit
      recording also has clear advantages for cross-correlation analysis. We show that
      the cross-correlation function between multiunit signals gives a reliable
      estimate of the average single-unit cross-correlation function. By the use of
      multiunit recording, it becomes much easier to detect relatively weak
      interactions between neurons at different cortical locations.

PMID- 15581713
TI  - Physiological studies of information processing in the normal and Parkinsonian
      basal ganglia: pallidal activity in Go/No-Go task and following MPTP treatment.
AB  - Understanding the role of the basal ganglia in day to day behavior is critical
      for a better understanding of the role of these structures in pathological states
      -such as Parkinson's disease. To elucidate this connection, we studied pallidal
      activity in a monkey performing a delayed release Go/No-Go task and in monkeys
      treated with the dopaminergic neurotoxin--MPTP. We compared the results with the
      predictions of the action selection and reinforcement driven dimensionality
      reduction models of the basal ganglia. The fraction of responding pallidal
      neurons, as well as the ratio of positive to negative responses, were equal in
      the Go and the No-Go modes. The fraction of pallidal neurons with significant
      responses following the trigger signal (19/26) was higher than that following the
      visual cue (11/26); however, the fraction of negative responses was significantly
      higher following the cue signal (47%) than that following the trigger signal
      (22%). Most (80%) of the cue responses were sensitive to the laterality of the
      cue, whereas only 25% of the responses following the trigger signal were
      sensitive to the cue or movement direction. Finally, pallidal spiking activity
      was not correlated in the normal behaving monkey, and became highly synchronized
      following MPTP treatment. We conclude that pallidal activity in the normal monkey
      is consistent with the model of action selection, assuming that action is
      selected following the visual cue. However, the reinforcement driven
      dimensionality reduction model is consistent with both the Go/No-Go responses and
      the normal/MPTP correlation studies.

PMID- 15581714
TI  - Rho proteins, mental retardation and the neurobiological basis of intelligence.
AB  - For several decades it has been known that mental retardation is associated with
      abnormalities in dendrites and dendritic spines. The recent cloning of eight
      genes which cause nonspecific mental retardation when mutated, provides an
      important insight into the cellular mechanisms that result in the dendritic
      abnormalities underlying mental retardation. Three of the encoded proteins,
      oligophrenin1, PAK3 and alphaPix, interact directly with Rho GTPases. Rho GTPases
      are key signaling proteins which integrate extracellular and intracellular
      signals to orchestrate coordinated changes in the actin cytoskeleton, essential
      for directed neurite outgrowth and the generation/rearrangement of synaptic
      connectivity. Although many details of the cell biology of Rho signaling in the
      CNS are as yet unclear, a picture is unfolding showing how mutations that cause
      abnormal Rho signaling result in abnormal neuronal connectivity which gives rise
      to deficient cognitive functioning in humans.

PMID- 15581715
TI  - Neurodevelopment, neuroplasticity, and new genes for schizophrenia.
AB  - Schizophrenia is a complex, debilitating neuropsychiatric disorder.
      Epidemiological, clinical, neuropsychological, and neurophysiological studies
      have provided substantial evidence that abnormalities in brain development and
      ongoing neuroplasticity play important roles in the pathogenesis of the disorder.
      Complementing these clinical studies, a range of cytoarchitectural, morphometric,
      ultrastructural, immunochemical, and gene expression methods have been applied in
      investigations of postmortem brain tissues to characterize the cellular and
      molecular profile of putative developmental and plastic abnormalities in
      schizophrenia. While findings have been diverse and many are in need of
      replication, investigations focusing on higher cortical and limbic brain regions
      are increasingly demonstrating abnormalities in the structural and molecular
      integrity of the synaptic complex as well as glutamate-related receptors and
      signal transduction pathways that play critical roles in brain development,
      synaptogenesis, and synaptic plasticity. Most exciting have been recent
      associations of schizophrenia with specific genes, such as neuregulin-1,
      dysbindin-1, and AKT-1, which are vital to synaptic development,
      neurotransmission, and plasticity.

PMID- 15581716
TI  - The impact of seizures on developing hippocampal networks.

PMID- 15581717
TI  - Alzheimer's disease as a disorder of dynamic brain self-organization.
AB  - Mental function is based on the dynamic organization of neuronal networks. In
      particular, phylogenetically young brain areas (e.g., cortical associative
      circuits), involved in the realization of "higher brain functions" such as
      learning, memory, perception, self-awareness, and consciousness, are continuously
      re-adjusted even after development is completed. By this life-long self
      optimization process, epigenetic information remodels the cognitive, behavioral
      and emotional reactivity of an individual to meet the environmental demands. To
      organize brain structures of increasing complexity during evolution, the process
      of selective dynamic stabilization and destabilization of synaptic connections
      becomes more and more important. The mechanisms of structural stabilization and
      labilization underlying a lifelong synaptic remodeling according to experience,
      are accompanied, however, by an increasing inherent potential of failure and may,
      thus, not only allow for the evolutionary acquisition of "higher brain function"
      but at the same time may provide the basis for selective neuronal vulnerability.
      The mechanisms of synaptic plasticity, i.e., of modifiable interneuronal
      connectivity, are largely based on external morphoregulatory cues and internal
      signaling pathways that nonneuronal cells have phylogenetically acquired to sense
      their relationship to the local neighborhood and to control proliferation and
      differentiation in the process of tissue repair and regeneration after
      development is completed. Differentiated neurons that have withdrawn from the
      cell cycle use these molecular machinery alternatively to control synaptic
      plasticity. The existence of these alternative effector pathways within a neuron
      puts it on the risk to erroneously convert signals derived from plastic synaptic
      changes into positional cues that will activate the cell cycle. This cell cycle
      activation potentially links synaptic plasticity to cell death. Preventing cell
      cycle activation by locking neurons in a differentiated but still highly plastic
      phenotype will, thus, be crucial to prevent neurodegeneration.

PMID- 15581718
TI  - [Concerning the anaesthesia record].

PMID- 15581719
TI  - [Quality assurance program for pain management after obstetrical perineal
      injury].
AB  - INTRODUCTION: A quality insurance program has been set up in order to improve the
      relief of pain in patients with perineal injury after childbirth. PATIENTS AND
      METHODS: The program has been developed according to the French standards of
      accreditation. After elaboration of a referential, a first study (103 patients)
      allowed to evaluate the ongoing practices and to appreciate the pain intensities.
      After analysis of the results, an action strategy has been elaborated, with a
      brand new therapeutic standard and a pain-monitoring program for nurses. Six
      months later, a second study (105 patients) measured the efficiency of the
      accomplished actions. The statistic analysis used chi2 and Kruskal-Wallis tests
      and a multivariate analyse (p <0.05). RESULTS: Several indicators led to conclude
      to the success of this program: analgesics prescribed systematically and earlier,
      best observance, larger utilisation of the NSAI, decrease of the analgesics
      requests, improvement of the satisfaction referred to the relief of pain. The
      multivariate analyse showed a risk twice as little as in the second study to have
      a 36th hour VAS score superior to four (p =0.03). CONCLUSION: The apply of this
      quality insurance program allowed to improve the analgesia after obstetric
      perineal injuries. A few adaptations are needed, and also more formations of the
      medical and paramedical staff. The durability of the accomplished actions shall
      be evaluated in the future.

PMID- 15581720
TI  - [Perioperative administration of betablockers: a practice survey].
AB  - OBJECTIVES: To evaluate the anaesthesiologists' attitude concerning the
      perioperative administration of betablockers (BB), especially prophylactic BB, in
      order to prevent postoperative cardiac complications. METHODS: A questionnaire
      including 20 items was sent to 700 anaesthesiologists of 4 French departments
      (Ain, Isere, Loire et Rhone). RESULTS: The response rate was 30%. Eighty-eight
      percent of respondents prescribed the BB with the premedication, on the day of
      the surgery in patients who were on regular BB. Before major surgery, 37% percent
      of respondents always or usually introduced prophylactic BB in patients with high
      cardiac risk. Atenolol was the drug of choice for 68% of perioperative BB users.
      Seventy-one percent of anaesthesiologists using prophylactic BB asked for a
      cardiologic opinion before starting BB therapy. CONCLUSION: In practice,
      anaesthesiologists continued BB during the perioperative period in patients who
      were on chronic treatment with BB. However, prophylactic perioperative
      administration of BB in patients with high cardiac risk is still inadequate and
      dependent on a cardiologic opinion.

PMID- 15581721
TI  - [What can be expected from off-pump coronary artery surgery?].
AB  - Coronary artery bypass surgery with beating heart (off-pump) has become more
      common in the last ten years allowing seven randomized studies with at least 60
      patients, comparing off-pump and on-pump coronary bypass. Anaesthesia, monitoring
      and haemodynamic complications are described. Randomized studies concluded to
      less elevation of biochemical markers of myocardial and renal injury, less hydric
      inflation, less cerebral microemboli, reduction of homologous blood transfusions,
      of hospital stay and global costs. However in low risk patients no reduction in
      myocardial infarction, atrial fibrillation, stroke, acute renal failure, early
      reoperation, surgical site infection and mortality were observed. Non-randomized
      studies suggest a benefit in stroke and mortality in elderly patients but the
      possibility of incomplete revascularization remains.

PMID- 15581722
TI  - [Morphine overdose due to cumulative errors leading to ACP pump dysfunction].
AB  - We report the case of a 67-year-female patient treated with a postoperative
      patient controlled analgesia using an Abbott Gemstar pump for after nephrectomy.
      In the postanaesthesia care unit, fifteen minutes after connecting with of the
      pump (which bag contained 100 mg of morphine) to the patient, respiratory arrest
      occurred. A morphine overdose was caused by uncontrolled delivery of the entire
      bag contents by free flowing due only to gravity. The patient was resuscitated
      immediately, and had uneventful recovery. This incident was the result of
      multiple misuse: one misconnection of the tubing between morphine bag and the
      patient thus shunting the antisiphon valve, and two an improper secured PCA
      cassette in an open position not detected by the pump. The tubing of these pumps
      and the software were subsequently modified by Abbott, which should reduce the
      risk of recurring incident. This accident points out that vigilance must remain
      rigorous in spite of widespread routine use of PCA.

PMID- 15581723
TI  - [Contribution of the brain natriuretic peptide in neurogenic pulmonary oedema
      following subarachnoid haemorrhage].
AB  - We report two cases of neurogenic pulmonary oedema following subarachnoid
      haemorrhage. A 58-year-old woman became increasingly dyspneic and needed oxygen
      support during a few days. A 53-year-old woman rapidly developed clinical and
      laboratory signs of respiratory failure, recovering in 48 hours. In both cases,
      chest radiography showed bilateral diffuse infiltrates, electrocardiogram
      revealed ST abnormalities, and cardiac troponin I level was elevated. In both
      patients, pro brain natriuretic peptide level was increased whereas global
      cardiac function was normal. The factors initiating its secretion are discussed.

PMID- 15581724
TI  - [Acute rhabdomyolysis due to butane inhalation. Report of two cases].
AB  - Prolonged inhalation of gas butane induced mostly neurological and cardiovascular
      symptoms. We reported two very rare cases of acute rhabdomyolysis caused by
      accidental prolonged inhalation of butane. The early diagnosis and the
      symptomatic treatment were associated with favourable evolution in the two cases.
      The mechanism of this complication is discussed and compared with the literature.

PMID- 15581725
TI  - [Recombinant activated factor VII as a life-saving therapy for severe postpartum
      haemorrhage unresponsive to conservative traditional management].
AB  - Postpartum haemorrhage remains the main cause of maternal morbidity and
      mortality. Treatment aims at maintaining hemodynamic circulation and preventing
      shock by stopping blood loss both medically and surgically. We report two cases
      of major postpartum haemorrhage due to uterine atony. Patients developed
      haemorrhagic shock and severe coagulation disorders (nadir values of PTT were
      <10% and fibrinogen was <0.1 g/l). Well-codified medical (ocytocin, sulprostone)
      and surgical management (ligation of both hypogastic arteries in the two cases
      completed by staged uterine ligation in one case) failed to stop bleeding.
      Recently, several case reports described successful use of recombinant activated
      factor VII (rFVIIa) in scheduled surgery, trauma and major postpartum
      haemorrhage. Thus, after transfusion of more than one blood mass and failure of
      surgical haemostasis to stop bleeding, rFVIIa (60 microg/kg) was given. A single
      iv bolus injection stopped ongoing diffuse haemorrhage in the two cases. No
      further transfusion was required afterwards in both patients. RFVIIa might thus
      be a strong complementary agent in the management of major postpartum
      haemorrhage. Optimal dose, timing and safety characteristics of rVIIa
      administration remain to be determined. One patient developed four weeks later
      thrombosis of both ovarian veins, a complication that can be related to either
      rFVIIa or to the staged uterine ligations performed during surgery.

PMID- 15581726
TI  - [Cervical post-traumatic pneumomyelogram: do not ignore this entity].
AB  - We report the case of a post-traumatic pneumomyelogram in a 51-year-old woman.
      The pneumomyelogram associated with a skull base fracture was revealed by
      systematic total body scan. The discovery of a traumatic pneumomyelogram will be
      probably more frequently discovered with the largest use of modern helical CT
      scan in traumatized patients. We discuss the etiologies and the implications for
      the anesthesiologist and the intensivist of this entity.

PMID- 15581727
TI  - [Laparoscopy under local anaesthesia and hypnoanaesthesia about 35
      cholecystectomies and 15 inguinal hernia repair].
AB  - OBJECTIVE: To present hypnosedation and the feasibility of this technique
      performed for laparoscopic procedure. STUDY DESIGN: Retrospective and descriptive
      study of feasibility. PATIENTS AND METHODS: Hypnosis can significantly reduce
      intraoperative requirements of intravenous sedation for surgery under local
      anaesthesia. Modifications of surgical procedure: laparoscopic surgery under
      local anaesthesia and hypnosis is performed using a subcutaneous lifting of
      anterior abdominal wall. Insufflation is only use to push out smoke. If patient
      or surgical uncomfort happens, moral contract with patient includes convert to
      general anaesthesia. RESULTS: We performed 35 cholecystectomies; 13 needed
      convert to general anaesthesia, mainly for peritoneal pain induced by CO(2)
      insufflation; 22 procedures were completed with patients' satisfaction. Upon 15
      hernia repairs, only one patient needed convert to general anaesthesia, for
      dissection difficulty. CONCLUSION: Probably hypnosis can't be extent to
      intraperitoneal laparoscopic procedures. On the other hand interest of hypnosis
      performed for extraperitoneal laparoscopic hernia repair must be explore.

PMID- 15581728
TI  - [Evolution of transfusion risks over a 15-year period (1987-2002)].
AB  - The majority of countries considered the consequences of post-transfusion
      infections to refer to HIV. However, the organisations and transfusion systems
      have been revised. The author's objective is now to measure the efficiency of
      these decisions with regards to risk prevention. The first step was to first draw
      up a list of these risks so as to obtain a definition which would be accepted
      throughout Europe. Having looked at the major tendencies between 1993 and 2002,
      the author made predictions for the following ten years. The ratios benefit-risk
      and cost-efficiency were also looked at.

PMID- 15581729
TI  - "Once a tetralogy of Fallot patient--always a tetralogy of Fallot patient (?)":
      time for reconsideration?

PMID- 15581730
TI  - "We are the world (of anaesthesia)": reflections on (and lessons learned at) the
      World Congress of Anaesthesiologists 2004.

PMID- 15581731
TI  - [Locoregional anesthesia in otorhinolaryngology: facial blocks].

PMID- 15581732
TI  - Stress-associated immune dysregulation and its importance for human health: a
      personal history of psychoneuroimmunology.
AB  - Historically, clinicians have suspected that both major and minor stressful
      events can have health implications. Observations and case reports link severely
      stressful life events with a sudden onset or worsening of a variety of illnesses.
      The immune system was quickly implicated as a means to help explain how stressful
      life events could produce this relationship. The field of psychoneuroimmunology
      (PNI) is a field of research that deals with the complex interactions between the
      central nervous system, endocrine and immune systems, and how behavior/stress can
      modify these interactions. In this review, I have selected some of our papers
      that represent our efforts to study the effects of stress on the immune response
      and also include selected papers that describe how our PNI program at The Ohio
      State University Medical Center has evolved; virtually all of this research has
      been performed in collaboration with Janice Kiecolt-Glaser and others in our
      research group.

PMID- 15581733
TI  - Role of the immune system in the maintenance of mouse facial motoneuron viability
      after nerve injury.
AB  - In the field of neuroimmunology, an emerging area of research involves the role
      that the immune system plays in neural injury and repair. Such immune:neural
      interactions may involve both neuroprotective and neurodestruction actions. To
      begin to address the compelling, and clinically relevant, issue of how the immune
      system impacts neural reparative processes, we combined the well described facial
      nerve injury paradigm, a simple neural injury model, with various immunodeficient
      mouse models, in order to delineate the contributing immune cells/factors
      involved in neural injury and repair. We have discovered a role for the CD4+ T
      cell in mediating facial motoneuron survival after facial nerve injury in the
      mouse. In this review, we present an overview of our work to date in this field
      and discuss future directions relevant to understanding key elements in the
      crosstalk between the immune:neural systems that develops subsequent to injury
      and/or trauma.

PMID- 15581734
TI  - Hepatitis C, depressive symptoms, viral load, and therapy: interactions and
      reactions.

PMID- 15581735
TI  - Depressive symptoms and viral clearance in patients receiving interferon-alpha
      and ribavirin for hepatitis C.
AB  - Interferon (IFN)-alpha plus ribavirin is an effective treatment for hepatitis C
      virus (HCV) infection, but is associated with a high rate of depression.
      Depression has been linked to a worse outcome in multiple medical disorders
      including viral illnesses. We examined whether increased symptoms of depression
      during IFN-alpha/ribavirin therapy were associated with a reduced treatment
      response as assessed by clearance of HCV. Depressive symptoms were evaluated in
      102 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of
      pegylated IFN-alpha-2b plus ribavirin therapy using the Zung self-rating
      depression scale (SDS). Viral clearance was determined at 24 weeks by polymerase
      chain reaction (PCR). Only 34% of subjects (10 out of 29) with a 20-point or
      greater increase in SDS Index score were HCV PCR negative at 24 weeks, compared
      to 59% (24 out of 41) of patients with a 10-19 point increase in SDS Index and
      69% (22 out of 32) of patients with a less than 10 point increase (chi2=7.6,
      df=2, p <0.05). In addition, a 20-point or greater increase in SDS Index score
      during IFN-alpha/ribavirin therapy significantly predicted failure to clear virus
      when considered alone [crude odds ratio (OR), 3.2; 95% confidence interval (CI),
      1.3-8.0; p <0.01] or when controlling for other factors that affected IFN-alpha
      treatment response (adjusted OR, 3.6; 95% CI, 1.3-9.5; p=0.01). These preliminary
      findings suggest that individuals who experience significant increases in
      depressive symptoms during IFN-alpha/ribavirin therapy may be less likely to
      clear virus, highlighting the importance of identifying and treating depressive
      symptoms in this patient population.

PMID- 15581736
TI  - Sleep-wake behavior and responses of interleukin-6-deficient mice to sleep
      deprivation.
AB  - Interleukin (IL)-1 and tumor necrosis factor (TNF) are involved in the regulation
      of non-rapid eye movements sleep (NREMS). Accumulating evidence suggests IL-6
      modulates sleep under some pathophysiologic conditions. We used mice lacking a
      functional IL-6 gene to investigate further a potential role for IL-6 in the
      regulation of sleep. IL-6 knockout mice (B6.129S6-Il6tm1Kopf; n=10) and C57BL/6J
      mice (n=10) were purchased from the Jackson Laboratory (Bar Harbor, ME). Twenty
      four-hour baseline recordings were obtained from mice in the absence of any
      experimental manipulation. Mice were then subjected to 6-h sleep deprivation
      beginning at light onset. Recordings were obtained during the deprivation period
      and for 18 h thereafter. During baseline conditions there were no differences
      between mouse strains with respect to the duration, timing or intensity of NREMS.
      However, across the 24-h recording period IL-6 knockout mice spent approximately
      30% more time in rapid eye movements sleep (REMS) than did C57BL/6J mice.
      Relative to C57BL/6J mice, core body temperatures of IL-6 knockout mice were
      higher during the light period of the light:dark cycle. Both strains responded to
      sleep deprivation by spending more time in NREMS and REMS. Although the total
      increase in the amount of NREMS after sleep deprivation was the same in both
      strains, IL-6 knockout mice took 6h longer to accumulate this additional sleep.
      Under the conditions of this study, IL-6 does not appear necessary for the full
      manifestation of NREMS, although this cytokine may influence the dynamics of
      responses to sleep deprivation. That mice lacking IL-6 spend more time in REMS
      suggests that interactions between IL-6 and REMS regulatory mechanisms may differ
      from those of IL-1 and/or TNF.

PMID- 15581737
TI  - Diurnal variation of lipopolysaccharide-induced alterations in sleep and body
      temperature of interleukin-6-deficient mice.
AB  - Infectious challenge triggers a broad array of coordinated changes within the
      host organism, including alterations in sleep-wake behavior and body temperature.
      Pro-inflammatory cytokines orchestrate many of the behavioral, metabolic, and
      endocrine responses to immune challenge. Although interleukin (IL)-6 mediates
      several aspects of sickness behavior, a role for this cytokine as a mediator of
      alterations in sleep in response to immune challenge has not been established. We
      evaluated sleep-wake behavior and core body temperature of IL-6-deficient (IL-6
      KO; B6.129S6-Il6tm1Kopf) mice and C57BL/6J control mice after intraperitoneal
      (IP) administration of 10 microg lipopolysaccharide (LPS). Because feedback
      mechanisms that regulate responses to immune challenge exhibit circadian rhythms,
      we evaluated responses to LPS administered at the beginning of both the light and
      dark portions of the light:dark cycle. LPS-induced increases in non-rapid eye
      movements sleep (NREMS) of both mouse strains, but this increase was less
      pronounced in IL-6 KO mice than in C57BL/6J mice. Strain differences in LPS
      induced increases in NREMS were greatest after light-onset administration. During
      the 12 h light period, NREMS of C57BL/6J mice increased from 53.0+/-1.7% of
      recording time after vehicle to 65.4+/-1.4% of recording time after LPS. During
      this same time period, NREMS of IL-6 KO mice increased from 50.5+/-1.8% after
      vehicle to only 52.4+/-1.8% of recording time after LPS. REMS of both mouse
      strains was suppressed to the same extent after LPS, irrespective of timing of
      administration. LPS-induced fever in C57BL/6J mice, with peak magnitude of 1.4+/
      0.3 degrees C and 1.8+/-0.2 degrees C after dark onset and light onset
      administration, respectively. In contrast, this dose of LPS-induced profound
      hypothermia in IL-6 KO mice, with nadirs of hypothermia reaching 4.9+/-1.0
      degrees C after injection at dark onset and 2.2+/-0.5 degrees C after
      administration at light onset. These results indicate that IL-6 mediates some of
      the effects of LPS on NREMS and body temperature of mice, and that the magnitude
      and duration of these effects differ as a function of the time at which the
      challenge is given.

PMID- 15581738
TI  - Avoidance behavior and neural correlates of allergen exposure in a murine model
      of asthma.
AB  - Allergic asthma is characterized by intermittent airway obstruction,
      inflammation, airway hyperreactivity, and increased production of IgE. The
      pathophysiology of asthma is well understood but little is known about its
      influences on brain activity and behavior. We recently described the neural
      correlates of food allergy and its associated modulation of behavior using an
      experimental model that also generates a T helper type 2 (Th2)-skewed response,
      with high levels of IgE. Here we show that mice allergic to ovalbumin (OVA) have
      an increase in the activity of the paraventricular nucleus of the hypothalamus
      (PVN) and in the central nucleus of the amygdala (CeA) following a single nasal
      OVA challenge. Moreover, we adapted a classical passive avoidance test using an
      OVA aerosol as the aversive stimulus. We found that allergic mice avoid entering
      the dark compartment of the apparatus that had been previously associated with
      nebulization of the allergen, while their non-immunized controls still move into
      the dark side of the test box. Thus, allergic mice have increased activity in
      areas of the CNS commonly associated with emotionality-related behavioral
      responses, such as the avoidance of a context previously associated with an
      unpleasant or harmful situation. Moreover, our findings on the avoidance test
      illustrate that previous experience with an airborne allergen can modify
      behavior.

PMID- 15581739
TI  - Social structure influences effects of pair-housing on wound healing.
AB  - Chronic stress or noxious stimuli delay wound healing in humans and rodents. The
      effects of stress on wound healing appear to be mediated by the hypothalamic
      pituitary-adrenal (HPA) axis and, in particular, increases in corticosteroids. As
      previously shown, positive social interaction faciltiates wound healing through
      suppression of corticosteroids. In the present study, we investigated the effects
      of pair-housing on wound healing and corticosteroid concentrations in three mouse
      species, the monogamous Peromyscus californicus, the facultative-monogamous
      Peromyscus eremicus, and the polygynous Peromyscus leucopus. Pair-housed P.
      californicus and P. eremicus had significantly smaller wounds than socially
      isolated cohorts. However, wound healing in P. leucopus was not affected by
      housing condition. P. californicus and P. eremicus mice that were pair-housed for
      2 weeks, then separated from their partners 48h prior to wounding also had wounds
      comparable to socially isolated mice. The benefits of social housing diminished
      when P. californicus and P. eremicus pairs were prevented from interacting
      physically via a double screen barrier. Two hours of daily restraint did not
      affect basal corticosterone concentrations or wound healing in either P.
      californicus or P. eremicus. In contrast, restraint facilitated wound healing in
      P. leucopus. Taken together, these data suggest that social contact facilitates
      wound healing in two monogamous, but not a polygynous, mouse species.

PMID- 15581741
TI  - The impact of early repeated pain experiences on stress responsiveness and
      emotionality at maturity in rats.
AB  - The intensive care necessary for premature newborns is characterized by multiple
      procedures, many of which are painful. Given emerging evidence that such early
      pain during this time of high brain plasticity may affect long-term
      neurodevelopmental and social-emotional functioning, this study explored the
      impact of early repeated pain on emotionality and stress responsivity at
      maturity. From birth through postnatal day 7, Fischer 344 pups underwent either
      paw needle prick every day versus every other day or daily paw touch, or were
      left unperturbed. Each paw received the designated perturbation once per day. At
      maturity, some animals underwent emotionality testing: either a 4-day series of
      open field exposures or a single elevated plus-maze (EPM) exposure. The paw prick
      groups exhibited less open field habituation and occupied the EPM open arms more.
      Two weeks later, all animals were either subjected to forced swim or not. At 1h
      post-swim, animals underwent either blood withdrawal for plasma corticosterone
      (CS) levels and ex vivo natural killer cell activity (NKCA) or were injected
      intravenously with radiolabeled NK-sensitive syngeneic MADB106 tumor cells and
      assessed for lung tumor retention. Sex was a major factor in the manifestation of
      perturbation-related differences in the biologic outcomes. Whereas postnatal pain
      differentially affected baseline tumor retention between males and females, only
      males exhibited perturbation-related differences in swim stress-induced increases
      in tumor retention and CS. Finally, male-female differences were evident in CS,
      NKCA, and tumor responses to swim stress. These findings suggest that early pain
      affects neurodevelopmental function in the mature organism; however, these
      relationships are complicated by sex differences, the postnatal pain schedule,
      and the outcome measured.

PMID- 15581740
TI  - Effects of amphetamine on NK-related cytotoxicity in rats differing in locomotor
      reactivity and social position.
AB  - The effect of i.p. administration of 1mg/kg of amphetamine (AMPH) on natural
      killer cells cytotoxicity (NKCC) and number of large granular lymphocytes (LGL
      NK) together with plasma corticosterone (CORT) level and WBC was evaluated in
      male Wistar rats differing in two behavioral features: locomotor reactivity to
      novelty (high, HR and low, LR responders) and social position (dominants, D and
      subordinates, S). In the majority of animals AMPH evoked (30 min after
      administration) an increase in NKCC and LGL (NK) number accompanied by
      lymphopenia, neutrocytosis, monocytosis, and an increase in CORT level. Changes
      in NKCC (LU20) showed substantial individual variability: in HR group
      approximately 513Delta%, p <0.01 (relative to the control); LR group
      approximately 56Delta%, p >.05; D group approximately 441Delta%, p >0.001; S
      group approximately 216Delta%, p >0.05; HR/D group approximately 643Delta%, p
      <.001; HR/S group approximately 414Delta%, p <.001; LR/D group approximately
      191Delta%, p >.05; and LR/S group approximately -19Delta%, p .05. The increase in
      CORT level, lymphopenia, and neutrocytosis indicated a stress-like reaction to
      AMPH. No significant correlation between NKCC and CORT level was found. The
      results obtained indicate that AMPH can evoke an increase in NK-related cytotoxic
      activity quantitatively related to high behavioral reactivity to novelty and
      social dominance, however NKCC is not related to the AMPH-induced CORT changes.

PMID- 15581742
TI  - Nesidioblastosis associated with hyperinsulinemic hypoglycemia in adults: review
      of the literature.
AB  - Nesidioblastosis is a term that was first introduced by Laidlaw in 1938 to define
      the diffuse proliferation of pancreatic islet cells budding from ductal
      epithelium. First described in neonates, it is widely recognized to be the
      primary cause of persistent hyperinsulinemic hypoglycemia in infants. In adults,
      insulinoma accounts for most cases of hyperinsulinemic hypoglycemia. Adult-onset
      nesidioblastosis associated with hyperinsulinemic hypoglycemia is a very rare
      entity, representing 0.5-5% of cases of organic hyperinsulinemia. Since 1981,
      when Harness et al. reported the first series of adult nesidioblastosis causing
      hypoglycemia, only 71 cases have been published. This article provides a guide
      for the diagnosis of organic hyperinsulinism and indicates when nesidioblastosis
      should be suspected. New diagnostic methods and treatment options for this rare
      disease are proposed. We also present a review of all reported cases of adult
      nesidioblastosis in the last 22 years.

PMID- 15581743
TI  - Gallbladder mucin plays a role in gallstone formation.
AB  - Mucin is a high-molecular-weight glycoprotein that is synthesized, stored, and
      secreted by epithelial mucosal cells, especially goblet cells. Mucin proteins are
      derived from many different genes, termed MUC genes. Several lines of evidence
      point to a biological role for mucin in cholesterol gallstone formation. Mucin
      serves as a pronucleating agent in experimental and human gallstone disease, and
      the hydrophobic binding sites in the polypeptide core of mucin may provide a
      favorable environment for nucleation of cholesterol monohydrate from
      supersaturated bile. Mucin hypersecretion is prominent in many animal models of
      gallstone formation, thus contributing by its pronucleating quality to gallstone
      formation. According to some research, mucin hypersecretion may also contribute
      to the formation of brown pigment stones. This may be explained in part by the
      findings that lipopolysaccharides derived from certain bacteria are effective
      stimulants of mucin secretion. Aspirin and nonsteroidal anti-inflammatory drugs
      inhibit gallbladder mucin secretion and prevent gallstone formation in animal
      models. Expanding our knowledge on mucin research may improve our understanding
      of the natural history of gallstone formation and enable the development of new
      treatment strategies.

PMID- 15581744
TI  - Determining the need for coronary revascularization by an exercise test
      assessment computer program (ETAP).
AB  - The rate at which coronary artery revascularization procedures are performed
      remains inconsistent, and their risks may be greater and long-term benefits less
      than imagined by the general public and open to considerable inter-individual
      variation. However, these risks and benefits can be explicitly estimated for an
      individual patient from a brief medical history and the results of a standard
      exercise test by a computer program that uses conventional medical decision
      making techniques. The program first estimates the prior and post-exercise test
      probability of coronary artery disease and then employs a decision analysis model
      to define the risks and benefits associated with different treatment options.
      These results are provided in a printed report that can become part of the
      clinical record to be reviewed with the patient. In contrast with traditional
      clinical intuition, the program consistently and explicitly defines the risks and
      benefits of coronary artery disease treatments. The program forces physicians and
      their patients to appraise critically the information and beliefs upon which they
      base their clinical decisions.

PMID- 15581745
TI  - Human T-lymphotropic virus type I/II infections in volunteer blood donors from
      Northern and Western Greece: increased prevalence in one blood bank unit.
AB  - BACKGROUND: Blood donors are routinely screened for antibodies to human T-cell
      lymphotropic viruses type I and II (HTLV-I and HTLV-II) in the United States,
      Canada, Japan, and some European countries. Previous reports from our group in
      relatively small numbers of donors have shown a zero prevalence of HTLV-I/II
      markers in our region. In this study, seven blood banks in the north and west of
      Greece participated in order to determine whether mandatory screening of blood
      donations for HTLV-I/II infection should be established. METHODS: Sera from
      51,714 consecutive donors were investigated for anti-HTLV-I/II using two
      commercially available enzyme immunoassays (EIAs). Reactive samples in one or
      both EIAs were repeatedly evaluated further by Western blot, which is specific
      for both confirmation and differentiation of HTLV-I and HTLV-II seroreactivities.
      Investigation for HTLV DNA was also done in all EIA-reactive donors, irrespective
      of the WB result, using a combination assay based on the polymerase chain
      reaction (PCR) and a DNA EIA. RESULTS: A total of 115 donors (0.222%; 95% CI
      0.018-0.26%) were initially considered reactive for anti-HTLV-I/II by EIAs.
      However, only 7 of the 115 were confirmed as positive by WB (five HTLV-I and two
      HTLV-I/II). Thus, the prevalence of anti-HTLV-I/II in donors from northern and
      western Greece was 0.013% (95% CI 0.003-0.023%). Interestingly, the majority of
      WB-confirmed anti-HTLV-positive individuals were detected in the blood bank of
      Corfu (5/7, all anti-HTLV-I). This prevalence (5/15383; 0.032%; 95% CI 0.004
      0.061%) was six times the prevalence found at the other blood banks combined
      (2/36331; 0.0055%; 95% CI 0-0.013%), but it was not statistically significant.
      None of the EIA-reactive donors had detectable HTLV DNA. CONCLUSIONS: The very
      low prevalence of confirmed anti-HTLV-I/II infection markers in northern and
      western Greek blood donors, together with the negative PCR results in EIA
      reactive subjects, indicates that anti-HTLV-I/I routine screening is not really
      justified in this area of our country. However, the increased prevalence of WB
      confirmed anti-HTLV-I-positive donors in the Corfu blood bank calls for further
      prospective and careful investigation in order to address whether this finding
      represents a real cluster phenomenon of HTLV infection.

PMID- 15581746
TI  - Vitamin C treatment reduces transcapillary escape rate of albumin in type 1
      diabetes.
AB  - BACKGROUND: Latent tissue scurvy in clinical and experimental ascorbic acid (AA)
      deficiency resembles diabetic microangiopathy as reflected in capillary
      hyperperfusion and increased transcapillary escape rate (TER), von Willebrand
      factor (vWf), and capillary fragility (CF). We aimed to investigate the possible
      clinical impact of the low plasma AA level observed in type 1 diabetes mellitus.
      METHODS: Twenty normoalbuminuric patients with retinopathy were included in a
      randomized, double-blinded, placebo-controlled 6-month study with AA (6 g/day;
      n=10, mean age+/-S.D. 35.3+/-8.5 years, diabetes duration 17.2+/-3.3 years) or
      placebo (n=10; mean age 37.8+/-6.6 years, diabetes duration 18.4+/-1.7 years).
      RESULTS: An inverse correlation between log plasma AA (HPLC method) and TER of
      (125)I-labelled albumin was found (r=-0.66, p=0.002). TER decreased in the AA
      treated group from 6.8+/-1.0 to 5.4+/-1.5%/h compared to the unchanged placebo
      group (from 5.6+/-1.5 to 5.9+/-1.1%/h; p=0.031). The CF (capillary resistance
      test) decreased in the AA group compared to the placebo group (p=0.028), while
      vWf, fibrinogen and fibronectin levels, and glomerular filtration rate (clearance
      of (125)I-iothalamate) remained unchanged. CONCLUSIONS: The results suggest that
      a low plasma AA level might be associated (pathogenetic?) with development of
      microangiopathy in type 1 diabetes mellitus and points to a possible treatment
      modality.

PMID- 15581747
TI  - The pattern and significance of abnormal liver function tests in community
      acquired pneumonia.
AB  - BACKGROUND: The pattern of liver function tests (LFTs) in community-acquired
      pneumonia has not been investigated in detail. Although abnormal tests are
      thought to be more frequent in patients with atypical pneumonia, the prognostic
      value of LFTs have not been clearly established. METHODS: We assessed 96
      consecutive patients admitted to one hospital with a chest infection over a
      period of 6 weeks. The infection was classified as bronchitis or lobar pneumonia
      on clinical and radiological criteria. The site and severity of the infection
      were assessed and correlated with LFTs and standard British Thoracic Society
      prognostic criteria. Mortality and length of stay in survivors were used as major
      outcome measures. RESULTS: There were 17 deaths (18%) overall and patients with
      abnormal LFTs were significantly more likely to die than those with normal tests
      (25% vs. 5%; p=0.026). Length of stay was significantly longer in survivors with
      abnormal liver function than in those with normal tests (9.7 vs. 5.8 days;
      p=0.006). A low albumin was the most useful predictor of poor outcome and carried
      a relative risk of dying of 1.8, comparable to the predictive value of
      tachypnoea. ALT was increased threefold in those succumbing to their disease, but
      alkaline phosphatase levels were not predictive of outcome and an increase in
      gamma GT appeared to be protective. CONCLUSIONS: Abnormal LFTs are common in
      community-acquired pneumonia and are of prognostic value. Patients with a low
      albumin or raised ALT are significantly more likely to die from their disease or
      to stay in hospital for a prolonged period. However, other LFTs are of less value
      in predicting prognosis.

PMID- 15581748
TI  - Adverse drug reactions due to prolonged antibiotic therapy for malignant external
      otitis.
AB  - BACKGROUND: Malignant external otitis (MEO) is a life-threatening infection
      requiring prolonged antibiotic therapy. Adverse drug reactions (ADR) occur
      frequently in patients treated with long-term antibiotics, often limiting
      treatment effectiveness. We attempted to identify and categorize the frequency
      and type of ADR in patients undergoing treatment for MEO in an attempt to improve
      overall treatment of individuals with this disorder. METHODS: Twenty-one patients
      with MEO who were treated during a 10-year period at our institution were
      identified retrospectively. Records were reviewed to determine demographic and
      clinical information as well as laboratory data. RESULTS: Overall, ADR occurred
      in six individuals (26.8%). Of the 15 patients who received ciprofloxacin
      therapy, none experienced ADR. In contrast, six of the nine patients who were
      treated with beta-lactam antibiotics experienced ADR including urticaria,
      elevated serum transaminase levels and neutropenia. CONCLUSIONS: Prolonged
      antibiotic therapy for MEO with beta-lactam antibiotics is more likely to be
      complicated by ADR and requires careful monitoring.

PMID- 15581749
TI  - Determinants of severity for superficial cellutitis (erysipelas) of the leg: a
      retrospective study.
AB  - BACKGROUND: Superficial cellulitis (erysipelas) of the leg is a frequent
      infectious disease with a favorable outcome, whereas some patients present a
      serious disease. The determinants of severity for superficial cellulitis
      (erysipelas) of the leg have not yet been clearly established. In order to
      determine the characteristics of patients presenting with severe superficial
      cellulitis of the leg, we analyzed patients with favorable and unfavorable
      outcome. METHODS: The records of 167 patients referred to Rouen University
      Hospital for non-superficial cellulitis of the leg were analyzed. Two severity
      groups of patients were retrospectively defined. Patients in the severe group
      either died secondary to infection during hospital stay or were hospitalized for
      a duration at least equal to the 90th percentile (i.e., >21 days of
      hospitalization). The remaining patients were considered as presenting with non
      severe cellulitis. Potential determinants of severity were analyzed by univariate
      and multivariate analysis based on logistic regression. RESULTS: From univariate
      analysis, the following general factors were positively associated with severity:
      advanced age, arterial hypertension, diabetes mellitus, elevated leukocytosis,
      and elevated neutrophilia. The local factors associated with severity were ulcer
      of the leg and arteriosclerosis obliterans of the leg. From multivariate
      analysis, only age (P=0.004), diabetes mellitus (P=0.01), and leukocytosis
      (P=0.04) appeared to be independently associated with severity. A close to
      significant association was also found with arteriosclerosis obliterans of the
      leg (P=0.07). Whereas general complications occurred more frequently in the
      severe group, no such difference was observed for local complications.
      CONCLUSIONS: Determinants of severity for superficial cellulitis of the leg
      include high age and associated medical conditions. Aged patients and patients
      with diabetes mellitus, elevated leukocytosis, or possibly arteriosclerosis
      obliterans of the leg should preferably be hospitalized for specific care of
      associated conditions to avoid the occurrence of general complications.

PMID- 15581750
TI  - Antineutrophil cytoplasmic antibody-associated neutropenia.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) can be associated with
      various disorders. However, their association with neutropenia has never been
      reported. METHODS: Nine patients with chronic unexplained neutropenia and ANCA
      were studied. Clinical charts were extensively analyzed and all patients
      underwent hematological and immunological investigations. RESULTS: All patients
      (6 women and 3 men) were Caucasian and had a mean age of 49 years (range 16-67
      years). All presented with a neutropenia below 1.5x10(9)/L for more than 6
      months. The neutropenia was <0.5x10(9)/L in six cases and moderate in three.
      There was no evidence of toxic- or drug-related neutropenia or of a hematological
      malignancy. Autoimmune anemia and/or thrombocytopenia were present in five
      patients. ANCA, with various specificities, were present in all patients. ANCA
      were associated with various other autoantibodies in eight patients, including
      antisurface-neutrophil antibodies in three cases. Four of the six patients with
      severe neutropenia experienced infections. Five patients were treated with
      hematopoietic growth factors, steroids, intravenous immunoglobulins, splenectomy,
      methotrexate and/or cyclophosphamide, allowing the neutrophil count to be
      restored transiently or permanently. CONCLUSIONS: A subset of patients with
      neutropenia of possible autoimmune origin may develop ANCA. Their detection would
      provide strong evidence of an autoimmune mechanism. Neutropenia should be added
      to the list of ANCA-associated diseases.

PMID- 15581751
TI  - Congenital spherocytosis with hereditary hemochromatosis without pathogenic
      mutations in the HFE gene.
AB  - We report a case of an 80-year-old woman with congenital spherocytosis who
      presented with massive iron overload. Iatrogenic iron overload could be ruled
      out. Familial history was suggestive of hereditary hemochromatosis; however,
      molecular genetic testing for the most common HFE mutations remained negative.
      The patient was treated successfully with phlebotomies. The hypothesis that this
      patient suffered from hereditary hemochromatosis is discussed on the basis of a
      brief review of the literature.

PMID- 15581752
TI  - SIADH consecutive to ciprofloxacin intake.
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is often
      drug-induced. We describe the first case, to our knowledge, of SIADH consecutive
      to ciprofloxacin administration. On two occasions, a 70-year-old patient, known
      for post-actinic bladder with repeated episodes of hematuria, was given
      ciprofloxacin and developed severe hyponatremia with seizures. On both occasions,
      the patient's condition improved rapidly after withdrawal of the drug. As all
      organic diseases likely to cause SIADH were excluded, and because the drug
      rechallenge was positive, we suggest that ciprofloxacin be added to the list of
      drugs prone to induce SIADH.

PMID- 15581753
TI  - Primary synovial sarcoma of the pleura: beware of misdiagnosis.
AB  - Primary synovial sarcoma of the pleura is an uncommon entity in the present
      medical literature. However, the paucity of documented cases may be due to
      misdiagnoses as a malignant mesothelioma in the past. Early diagnosis with new
      molecular techniques may improve the outcome of this tumour, which is believed to
      have a grave prognosis at present.

PMID- 15581754
TI  - A case of multiorgan Langerhans' cell histiocytosis presented with pneumothorax.
AB  - Pulmonary Langerhans' cell histiocytosis (LCH) represents an uncommon clinical
      disorder with unpredictable clinical presentation and outcome. Lung involvement
      may occur either in isolation or as part of a multiorgan disease. A 43-year-old
      woman was admitted to our hospital with acute left chest pain and shortness of
      breath. Spontaneous left pneumothorax was detected. All laboratory tests,
      including pulmonary function studies, were normal. Radiological findings posed
      high suspicion for LCH and lung biopsy confirmed this diagnosis. Further studies
      identified small cystic lesions in the scalp and liver. The diagnosis of multiple
      organ LCH involvement was made. Spontaneous pneumothorax might be the presenting
      clinical symptom of LCH. The present case emphasizes the capricious nature of LCH
      and the importance of an individualized therapeutic approach.

PMID- 15581755
TI  - Bilateral pulmonary infiltrates in a patient with ulcerative colitis receiving
      mesalazine.
AB  - A 36-year-old woman presented with a 2-month history of dry cough, bilateral pain
      in the upper chest, and low-grade fever. She had a 1-year history of ulcerative
      colitis (UC), which was treated with mesalazine. Cultures of sputum and
      bronchoalveolar lavage (BAL) fluid were negative. Chest radiograph and a computed
      tomography (CT) scan showed dense bilateral subpleural infiltrates in both upper
      lobes. A c-ANCA test was positive in a 1:1280 titer, and further specification
      showed antibodies against proteinase-3 antigen. Due to the possibility of
      mesalazine toxicity, this medication was stopped. Within 2 weeks, the patient's
      symptoms markedly improved, together with the chest roentgenogram.

PMID- 15581756
TI  - Acanthosis nigricans associated with acute myeloid leukaemia.

PMID- 15581757
TI  - Macrolide-induced Churg-Strauss syndrome.

PMID- 15581759
TI  - Methodology and reporting of randomised controlled trials.
AB  - A systematic review of the literature will fail to provide information needed for
      evidence-based medicine (EBM) if the design, execution and reporting of
      individual trials do not adhere to strict guidelines. Experience gained while
      conducting systematic literature reviews have revealed serious shortcomings in
      current literature. These limitations pertain to randomisation, blinding, outcome
      assessments and data reporting. The principles related to these issues are
      discussed with solutions and improvements provided.

PMID- 15581760
TI  - Anterior cruciate reconstruction combined with valgus upper tibial osteotomy: 12
      years follow-up.
AB  - A retrospective review of 29 patients (30 knees) was carried out who had
      previously undergone a single-stage combined ACL reconstruction with valgus upper
      tibial osteotomy for chronic ACL rupture coupled with early medial tibio-femoral
      arthritis. Of the 30 knees, 19 (63%) had had a previous medial meniscectomy.
      Major complications occurred in two knees resulting in stiffness. At a mean of 12
      years follow-up (6-16 years) only five knees (17%) had progressed one arthritis
      grade. Fourteen patients (47%) returned to intensive sports, and a further 11
      (37%) played moderate sports. The mean difference in anterior tibial translation
      with the opposite normal knee was 3 mm at review. It was concluded that the
      combined operation has a low morbidity, controls anterior laxity, allows many
      patients to return to sports, and does not result in a rapid progression of
      osteoarthritis.

PMID- 15581761
TI  - Fifteen to twenty-eight years' follow-up results of high tibial valgus osteotomy
      for osteoarthritic knee.
AB  - A long-term follow-up study was performed on 75 knees of 53 patients after high
      tibial valgus osteotomy. The earlier results have previously been reported. There
      were 15 knees in 11 men and 60 knees in 42 women. The follow-up period ranged
      from 15 to 28 years with a mean of 19 +/- 3 years. The age at osteotomy ranged
      from 46 to 73 years with a mean of 59.6 +/- 6.7 years. The diagnosis was medial
      compartmental osteoarthritis (OA) in 68 knees (46 patients) and spontaneous
      osteonecrosis of the medial femoral condyle in 7 knees (7 patients). Valgus
      osteotomy was performed above the tibial tuberosity, with removal of a laterally
      based wedge in all cases, aiming for anatomical valgus angulation of 10 degrees .
      The American Knee Society Score showed a Knee Score of 37 +/- 20 and a Function
      Score of 38 +/- 16 preoperatively and 87 +/- 13 and 80 +/- 19 at the final 15 to
      28 years' follow-up. The femoro-tibial angle in standing was 186 +/- 6.5 degrees
      (6 degrees of anatomical varus angulation) before and 171 +/- 7.5 degrees (9
      degrees of anatomical valgus angulation) at final follow-up (p < 0.0001), with no
      apparent loss of limb alignment.

PMID- 15581762
TI  - Femoral shaft osteotomy for malunited femoral fractures presenting with varus OA
      of the knee.
AB  - Seven patients presenting between 1992 and 1999 with osteoarthritic knee symptoms
      in consequence of old malunited femoral shaft fractures, were treated by open
      femoral shaft osteotomy. The osteotomies were sited at the apex of the deformity
      and were fixed by locked intramedullary nailing. The patients were followed up
      until osteotomy union and reviewed clinically and radiologically with particular
      emphasis on symptoms and function. The mean age at presentation was 48 years and
      the mean time from fracture was 28 years. The mean time to osteotomy union was 28
      months. Five of the seven patients reported excellent pain relief and functional
      improvement. These patients presented a difficult management problem at an age
      that would be worryingly young for total knee replacement. Arthroplasty has been
      avoided in all but one of this cohort, and is still far from imminent in the
      remainder, after a mean follow-up period of 5 years.

PMID- 15581763
TI  - Tricalcium phosphate granules or rigid wedge preforms in open wedge high tibial
      osteotomy: a radiological study with a new evaluation system.
AB  - The capacity of two forms of porous beta-tricalcium phosphate bone substitutes
      (TCP) to promote bone healing in open wedge high tibial osteotomy (OWHTO) was
      studied. We reviewed the X-rays of 27 osteotomies, with either TCP wedges or TCP
      granules as filling material, to compare the bone healing rates and bone
      remodelling, at specific postoperative intervals. A new radiologic rating system
      for OWHTO was created and tested for clinical applicability. All osteotomies
      healed uneventfully and complete resorption of TCP was demonstrated at 1 year
      postoperative in 85% (n = 23) of the procedures. In 44% (n = 10) of these 23
      procedures, the osteotomy site was no longer visible. No difference in bone
      healing rate and bone remodelling was found when comparing the use of granules to
      a wedge, and no adverse effects of TCP were observed. The good inter- (k = 0.7)
      and intraobserver (k = 0.6) reliability of the new radiologic rating system
      enables clinical use. Good bone healing was found in OWHTO with both wedges and
      granules of TCP.

PMID- 15581764
TI  - Distal tuberosity osteotomy in open wedge high tibial osteotomy can prevent
      patella infera: a new technique.
AB  - To prevent patella infera in open wedge high tibial osteotomy, a new operation
      technique was developed. Instead of a proximal tibial tuberosity osteotomy, a
      distal osteotomy was performed and the tuberosity was fixed with one screw to the
      tibia. Initial experience in 17 patients was evaluated and compared with results
      of 20 patients with open wedge high tibial osteotomy with proximal tuberosity
      osteotomy. Distal tuberosity osteotomy in open wedge high tibial osteotomy
      appears effective in preventing patella infera.

PMID- 15581765
TI  - A review of wound healing following Maquet osteotomy.
AB  - Maquet osteotomy can be associated with an unacceptably high incidence of wound
      complications that may be as high as 37%. A consecutive series of 42 Maquet
      osteotomies has been performed between 1990 and 2002 by a single surgeon without
      a single wound problem or infection and this series is the subject of this
      report. The use of an anterolateral incision reduces the damage to the major
      lymphatics minimising the risk of wound oedema. Identification and preservation
      of the feeding musculocutaneous vessels on the lateral and medial sides
      facilitates extensive but safe mobilisation of the skin flaps permitting an easy
      closure over a substantially elevated tibial tubercle. The use of an
      anterolateral incision with knowledge of the blood supply of the leg has
      eliminated the wound complications associated with the standard anteromedial
      incision reported previously in the literature. This approach, preserving the
      blood supply and lymphatic drainage, avoids skin necrosis and wound dehiscence,
      obviates any requirement for plastic surgical procedures such as releasing
      incisions or skin grafts and minimises the risk of infection and osteomyelitis.

PMID- 15581766
TI  - Salvage revision total knee replacement using the Endo-Model rotating hinge
      prosthesis.
AB  - Inability to balance a knee in complex revision total knee replacement has led to
      the use of rotating hinged knee devices in these cases as a salvage procedure. We
      conducted a retrospective study of 50 patients receiving 51 Endo-Model rotating
      hinge prosthesis with an average follow-up of 4 years (range 2-6 years). Clinical
      and radiological results were reviewed at latest follow-up. Five patients died
      from unrelated causes. Reasons for revision were infection (23), aseptic
      loosening (23), implant failure (3), stiffness (1) and peri-prosthetic fracture
      (1). The average number of previous surgery from and including the primary
      arthroplasty was three (ranges 1-14). Seven patients required plastic surgery for
      soft tissue cover. There was notable improvement in the pain, stability, range of
      motion and mobility of the patients with an improvement in the Hospital for
      Special Surgery Score (35.9 to 72.17). Postoperatively, 11 (22%) had an excellent
      HSS grade, 22 (44%) good grade, 10 (19%) fair grade and 8 (15%) poor grade. A
      significant number of our patients had an extremely low preoperative HSS score,
      and for these patients, an improvement to a fair grade HSS score was a
      satisfactory and realistic outcome. Forty-four (86%) patients were satisfied with
      the outcome of the revision surgery, 3 (6%) noncommittal and 4 (8%) disappointed.
      Comparing revision for infection vs. aseptic loosening, 22 (95%) patients out of
      23 were satisfied in the aseptic loosening group vs. 17 (74%) out of 23 were
      satisfied in the infected group. In selected complex cases, salvage revision
      surgery shows encouraging results in the short to medium term using the Endo
      Model rotating hinge prosthesis. A knee score such as the Hospital for Special
      Surgery score (objective outcome) should be used in conjunction with a patient
      satisfaction questionnaire (subjective outcome) in assessing the clinical outcome
      of complex, salvage revision knee surgery. Revision for infected total knee
      replacement is less likely to produce a satisfactory outcome as compared to
      revision for aseptic loosening.

PMID- 15581767
TI  - Customised hinged knee replacements as a salvage procedure for failed total knee
      arthroplasty.
AB  - BACKGROUND: Failure of knee arthroplasty can lead to significant pain and
      functional disability. In a small number of patients with fracture, sepsis or
      massive bone loss they are considered for arthrodesis or above knee amputation.
      The purpose of this study was to investigate the results and complications of
      using customised hinged knee replacements in their place. METHODS: Since 1993, 30
      of the 280 (10.7%) revision knee replacements in the Avon Orthopaedic Centre,
      Bristol have used Endo customised hinged knee prostheses (21 rotating, nine
      fixed) for salvage of limb threatening situations in elderly patients. Surgical
      indications were 22 low periprosthetic fractures (with or without aseptic
      loosening), five massive aseptic osteolyses, and three deep infections. RESULTS:
      The mean length of post-operative hospital stay was just 14.6 days and all
      patients were discharged walking with aids. At follow up (mean 3.0 years, range
      0.5-9.3 years) nine patients had died with their prostheses in situ and
      functioning. Six patients developed deep sepsis, two of which underwent above
      knee amputation, and two had received further surgery for septic problems. Two
      patients required further surgery for prosthetic disarticulation and one patient
      had successful on table vascular repair. Twenty-five patients had mid- or long-
      term follow up. Their mean American Knee scores (AKS) were 69.8 for knee and 35.6
      for function (maximum 100), with mean total knee flexion 83 degrees. Mean Oxford
      knee scores (OKS) and WOMAC scores (both scored between 12 and 60 with low score
      indicating less difficulties) were 34.0 and 30.5, respectively. CONCLUSIONS:
      Customised hinge revision knee replacements gave rapid rehabilitation and
      hospital discharge. Complications were high but at mid- and long-term review, no
      prostheses had failed from an aseptic cause and most of the knees of this
      challenging group were providing both stability and flexion.

PMID- 15581768
TI  - Total knee arthroplasty in a patellectomised posterior cruciate ligament
      deficient knee: a new technique of patellar tendon bone grafting.
AB  - Total knee arthroplasty in patients with previous patellectomy are less
      successful because of anteroposterior instability, residual pain and the loss of
      the mechanical advantage of the patella. To restore the moment arm of the
      quadriceps, the senior author (C.W.) described the technique of bone grafting the
      patellar tendon in a patient using the tibial plateau obtained from the routine
      tibial cut during total knee arthroplasty. The tibial eminence was used as the
      interfacetal ridge of the 'created' patella. At follow-up, the results were
      excellent with a postoperative knee society score of 90 and a postoperative
      patient functional score of 92. Radiological investigations showed a well
      incorporated graft in the patellar tendon.

PMID- 15581769
TI  - Total knee replacement in patients with multiple sclerosis.
AB  - Total knee replacement was performed on two patients with Multiple sclerosis.
      Severe hamstring spasticity was encountered in both patients in the immediate
      post-operative period requiring further surgery. Both patients remain ambulatory
      at follow-up. The disease, and its implications in patients warranting total
      joint replacement are discussed.

PMID- 15581770
TI  - Treatment of proximal fibular tumors with en bloc resection.
AB  - Proximal fibular tumor resection has always been a challenge to an orthopedic
      surgeon due to the proximity of two major structures; the peroneal nerve and
      anterior tibial artery. Extra-articular resection of the proximal tibiofibular
      joint, sacrificing of peroneal nerve and split resection of lateral tibial wall
      are major points of debate. Malawer described two types of resection for
      aggressive benign and malignant tumors of the proximal fibula, type I for benign
      and type II for malignant tumors. Between 1992 and 2002, nine male patients with
      proximal fibula tumors were treated by en-bloc resection as described either by
      Malawer and or by one of two new resection techniques. Of the nine tumors, six
      were diagnosed as giant cell tumor (one of them recurrent), two as osteosarcoma
      and one as benign fibrous histiocytoma. The mean age of the patients was 23.6 (20
      48) years. The mean follow up period was 42.8 months (15-117). There were no
      complications leading to a secondary surgical procedure+no local recurrence.
      Tumor volume was over 250 ml in two GCT cases, so the deep peroneal nerve was
      sacrificed to provide a wide margin. Iatrogenic peroneal nerve palsy developed in
      two patients. Late tendon transfers were performed for the management of drop
      foot. Our results indicate that if tumor is recurrent or has a large volume, wide
      resection (including deep peroneal nerve) should be done. Despite satisfactory
      tumor management, functional outcomes turned out to be variable, therefore
      precise ligament and muscle reconstruction is recommended.

PMID- 15581771
TI  - Popliteal artery entrapment syndrome: an unusual presentation of a fibular
      osteochondroma.
AB  - This report describes a fibular neck osteochondroma presenting as popliteal
      artery entrapment syndrome.

PMID- 15581772
TI  - An unusual complication of knee arthroscopy: portal site synovial cyst.
AB  - We describe a previously un-reported case of a large synovial cyst developing in
      the portal site 10 years post knee arthroscopy. The pathology, indications and
      method of treatment are discussed.

PMID- 15581773
TI  - Response to Editorial Review: UKR-Time for caution? (vol 11, 2004, p. 337-339).

PMID- 15581775
TI  - Guidelines for screening and treatment of cervical disease in the adolescent.
AB  - BACKGROUND: The last decade has seen a significant increase in our knowledge of
      HPV infection and its natural history. The advent of liquid-based cytology and
      HPV testing has changed the way we approach patients with abnormal Pap tests. The
      objective is to summarize some of the key evidence that lead to the American
      Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for the
      management of abnormal cytology and histology and the American Cancer Society
      (ACS) cervical cancer screening guideline as they pertain to adolescents.
      METHODS: The critical publications responsible for the recent ASCCP guidelines as
      well as the ACS recommendations for cervical cancer screening were reviewed.
      RESULTS: Sexually active adolescents are frequently infected by HPV. The natural
      history of these infections is one with a high rate of resolution. The typical
      HPV infection will resolve in approximately one year. The ACS has recommended
      that Pap test screening begin at 21, or 3 years after the onset of sexual
      activity. The ASCCP guidelines for the management of CIN 1 conclude that
      observation is the preferred therapy. These recommendations reflect our improved
      understanding of the natural history of HPV infection. CONCLUSIONS: Adolescents
      frequently experience transient HPV infections. As our understanding of the
      natural history of these infections has improved major national organizations
      have changed the recommendations for the screening of cervical disease and
      treatment of low-grade cervical abnormalities. The health care community
      servicing adolescents should incorporate these recommendations into daily
      practice.

PMID- 15581776
TI  - Characteristics of adolescent street youth with a history of pregnancy.
AB  - This study examines characteristics of adolescent street youth with histories of
      pregnancy and documents important factors that merit consideration when providing
      global sexual health care. STUDY OBJECTIVE: To determine social and behavioral
      factors associated with a history of pregnancy among adolescent street youth.
      DESIGN, SETTING, PARTICIPANTS: In a prospective cohort study, female adolescent
      street youth (14-19 years) ever pregnant (AEP) were compared with adolescents
      never pregnant (ANP) using data from baseline questionnaires. RESULTS: Among the
      225 participants, 41.8% were ever pregnant. Both groups were similar with respect
      to age (mean 17.8 years) and other socio-economic characteristics. However, AEP
      were more likely to have been kicked out of home (62.8% vs. 47.3%, P=0.022) and
      to have run away (78.7% vs. 64.9%, P=0.025) and were homeless younger (mean age:
      13.9 vs. 14.7 years, P=0.011) and since a longer period (mean: 4.0 vs. 3.0 years,
      P=0.001). Both groups had problematic alcohol and drug use: 31.3% had a CAGE
      score >2; 72.2% had a DAST score >6. Almost half (44.0%) had ever injected drugs
      and AEP were younger at initiation into drug injection (15.2 years vs. 16.0
      years, P=0.049). More AEP had experienced intra-familial or extra-familial sexual
      abuse (71.3% vs. 56.5%, P=0.024), and had had more than one abuser (71.6% vs.
      50.0%, P=0.009). Among those abused by family members, abuse occurred at an
      earlier age for AEP (mean age: 7.4 vs. 8.9 years, P=0.090) and more AEP reported
      severe abuse: vaginal penetration (62.2% vs. 26.7%, P=0.004) and anal penetration
      (29.7% vs. 3.3%, P=0.005). CONCLUSIONS: Histories of severe sexual abuse and
      early injection drug use are extremely frequent in ever pregnant street
      adolescents. These factors need to be addressed when planning global health care
      and sexual health education.

PMID- 15581777
TI  - Adolescence and abortion in Greece: women's profile and perceptions.
AB  - PURPOSE: To investigate the individual and social profile of the adolescents
      seeking abortion in Greece. PROCEDURES: Questionnaires were distributed from the
      obstetricians practicing in the capital and two major cities in Greece to
      adolescent pregnant women who were seeking for abortion and collected
      anonymously. MAIN FINDINGS: From 150 consecutive pregnant adolescents, 38 refused
      to participate and from 112 who accepted to participate only 74 (66%) replied.
      Most of the respondents lived in a city (65%), were unmarried (73%), 62% had sex
      first time after the age of 15, and the educational status of their parents was
      rarely at higher degree (father: 20%, mother: 16%). Among them, 74% declared that
      they had received information on contraception (64% from friends, 47% from
      doctors, 36% from the media). Overall, withdrawal (49%) and male condom (28.5%)
      were the popular contraceptive precautions. Abortion was adolescents' decision in
      65%, while the partner's influence in the case of a shared decision was as high
      as 73%. Most adolescents (91%) knew about the potential risks of abortion mainly
      by their doctor (87%) and socio-economical reasons (89%) were mostly claimed.
      Their parents were rarely aware about their pregnancy (28%) and decision for
      abortion (28%). In most cases it was the first abortion (78%) and adolescents
      declared that were aware about the Greek Church's opposition (89%) and the
      existence of an abortion law (86%). PRINCIPAL CONCLUSION: In Greece, the poor
      education on the issue of contraception still remains a major problem among
      teenagers contributing to the increased prevalence of undesired pregnancies and
      abortions.

PMID- 15581778
TI  - Effects of a surgical treatment of congenital cervicovaginal agenesia.
AB  - OBJECTIVE: Congenital agenesis of the uterine cervix and vagina is one of the
      rarest congenital defects. The objective of this manuscript is to present our
      experience and effects of a surgical treatment in five girls with inborn agenesis
      of the uterine cervix and vagina, who were operated in our clinic. METHOD: The
      vagina is reconstructed in four stages: (1) formation of vaginal recess; (2)
      phantomization of vagina; (3) joining of the reconstructed vagina with the
      uterus; (4) revision and correction of the junction. GnRH analogs were
      administered to avoid menstrual blood flow into the peritoneal cavity during
      phantomization. RESULTS: Patency of the uterovaginal junction was maintained with
      a #6 intubation tube. Normal menstruation was restored in all patients. Atresion
      of the canal at the uterovaginal junction was disclosed after 3-8 months in three
      of the patients. Patency was restored with surgical hysteroscope and the canal
      was mechanically distended. Clinical and ultrasonographic followup in the
      patients will continue.

PMID- 15581779
TI  - Comparison of nucleic acid amplification tests and culture techniques in the
      detection of Neisseria gonorrhoeae and Chlamydia trachomatis in victims of
      suspected child sexual abuse.
AB  - STUDY OBJECTIVES: (1) To identify factors predictive for gonorrhea and chlamydia
      positivity by LCR testing based on history and physical findings encountered
      during the sexual abuse evaluations. (2) To compare Ligase Chain Reaction (LCR),
      Polymerase Chain Reaction (PCR), and culture methods in the detection of
      chlamydia and gonorrhea infection among prepubertal and adolescent girls referred
      for sexual abuse evaluations. DESIGN: Prevalence odds ratios and logistic
      regression analysis were used to identify factors among patients' physical
      symptoms and signs, history of sexual activity, and abuse characteristics that
      were associated with positive test results for gonorrhea and chlamydia. The Kappa
      statistic was used to perform pairwise comparisons of LCR, PCR, and culture
      identification of gonorrhea and chlamydia infection. SETTING: A specialized
      sexual abuse clinic in San Antonio, Texas. PARTICIPANTS: A consecutive sample of
      229 girls between the ages of 6 and 20 who reported, or had indicators of,
      abusive genital-genital or genital-anal contact. MAIN OUTCOME MEASURES: Patients'
      history and physical findings predicting positive test results for gonorrhea and
      chlamydia infection; and relative sensitivity of testing sites (vaginal swab and
      urine) and methodologies (LCR, PCR, and culture) in identifying gonorrhea and
      chlamydia infection. RESULTS: (1) Gonorrhea infection: 3.2% of subjects were
      positive for gonorrhea by LCR at one or more sites; 2.4% had positive gonorrhea
      cultures. There was excellent agreement between vaginal swab LCR and PCR;
      agreement between urine samples was limited by the small number of positive
      tests. The sole factor that predicted gonorrhea positivity was increased number
      of white blood cells seen on wet mount. (2) Chlamydia infection: 11.1% of
      subjects were positive for chlamydia by at least one LCR test; only 0.8% had
      positive chlamydia cultures. Both urine and vaginal swab testing showed good
      agreement between PCR and LCR but not between culture and either of the newer
      methodologies. Factors that predicted chlamydia positivity were: patient history
      of consensual sexual contact, patient history of vaginal discharge, and the
      presence of concerning or definitive findings of genital trauma. CONCLUSIONS:
      While LCR, PCR, and culture techniques appeared comparable for detecting
      gonorrhea, LCR techniques detected significantly more patients with chlamydia
      infection when compared with the culture technique. PCR was comparable to LCR in
      detecting chlamydia infection. The LCR vaginal swab detected more patients with
      chlamydia and gonorrhea than the LCR urine sample. Risk factors for chlamydia and
      gonorrhea infection were present in most, but not all, of the children with
      positive LCR findings. LCR and PCR appear to detect more chlamydial and
      gonorrheal infections than do cultures.

PMID- 15581780
TI  - The Electronic Report on Adolescent Pregnancy (ERAP).
AB  - PURPOSE: To create a data management system that: (1) standardizes antecedent,
      program, and outcome variables relevant to the shared goals of adolescent
      oriented maternity programs while allowing users to add variables pertaining to
      unique aspects of their work; (2) cues providers to physiologic and psychosocial
      characteristics that predispose teenagers to adverse pregnancy and parenting
      outcomes, (3) standardizes patient care by guiding providers through adolescent
      oriented prenatal, postpartum, and well baby visits, and (4) establishes the
      infrastructure to collect data from a nationally representative sample of
      pregnant and parenting teens. METHOD: We adapted a powerful, state-of-the-art
      relational database framework (Microsoft Access 2000) to create an easy-to-use
      data management system-The Electronic Report on Adolescent Pregnancy (ERAP)-that
      requires minimal training to use on a personal computer. RESULTS: ERAP is
      designed to meet the administrative and analytic needs of adolescent-oriented
      maternity programs. It consists of six linked core data tables (teen, pregnancy,
      prenatal visits, child, interconception interval, and interconception interval
      visits), that allow users to analyze data from these multiple views while
      preserving the family structure. In addition, the database standardizes methods
      for collecting and storing the information and automatically computing the
      variables needed to monitor and evaluate an adolescent-oriented maternity
      program. Since by adding variables and appending supplementary tables, users can
      modify the core database to accommodate unique aspects of their programs and/or
      research, ERAP is also an ideal conduit for translating research findings into
      clinical practice. Similarly, because ERAP actually structures the care patients
      receive, the database provides the infrastructure needed to develop and implement
      best practice guidelines for treating teen-headed families. Finally, the
      confidentiality of all subject data is assured because ERAP is password-protected
      and automatically prepares files for batched external analyses by removing
      personal identifiers. CONCLUSIONS: ERAP provides the infrastructure needed to
      create a teen-pregnancy databank at the national level and an efficient patient
      monitoring system at the program level. By standardizing variable definitions and
      data collection techniques, serving as a repository for data collected at
      multiple sites, and tracking the multidisciplinary aspects of the care patients
      receive, ERAP has the potential to facilitate collaboration between adolescent
      oriented maternity programs, increase the scientific rigor of teen pregnancy
      research, and improve the quality of care individual teen-headed families receive
      by prompting compliance with best practice guidelines.

PMID- 15581781
TI  - Hematocolpos associated with a remote history of chronic vaginitis and a
      diagnostic vaginal biopsy: a case report.
AB  - Bacterial vaginitis is commonly seen in the pediatric population. Severe or
      recurrent cases may be associated with ulcerative lesions. We report a case of
      vaginal biopsies of ulcerative lesions in a 9-year-old which led to severe
      vaginal adhesions, stenosis, and hematocolpos. A vaginoscopy and resection from
      below were not successful and an exploratory laparotomy with uterine perforation
      and sounding into the upper vagina were required to reopen the lower vaginal
      canal. We recommend the limited use of vaginal biopsies in the face of a typical
      vaginitis presentation, and aggressive treatment to promote mucosa healing when
      biopsies are required.

PMID- 15581782
TI  - Tubo-ovarian abscess mimicking ovarian tumor in a sexually inactive girl.
AB  - Tubo-ovarian abscess is a serious complication of pelvic inflammatory disease
      rarely seen in sexually inactive girls. Early diagnosis and treatment are
      essential to prevent further sequela including infertility, ectopic pregnancy,
      and chronic pelvic pain. We present a case of 19-year-old sexually inactive girl
      who presented with abdominal pain and pelvic mass resembling ovarian tumor.
      Unilateral tubo-ovarian abscess with extensive bowel adhesions was determined at
      laparotomy. Drainage of the abscess and postoperative antibiotic therapy cured
      the patient.

PMID- 15581783
TI  - Management Quandary. Vulvar nevi in children.

PMID- 15581784
TI  - Help the adolescent patient quit smoking.

PMID- 15581785
TI  - The female athlete triad.

PMID- 15581786
TI  - De-mystifying what's up down there.

PMID- 15581787
TI  - Nutrient sensing and metabolic decisions.
AB  - Cells have several sensory systems that detect energy and metabolic status and
      adjust flux through metabolic pathways accordingly. Many of these sensors and
      signaling pathways are conserved from yeast to mammals. In this review, we bring
      together information about five different nutrient-sensing pathways (AMP kinase,
      mTOR, PAS kinase, hexosamine biosynthesis and Sir2), highlighting their
      similarities, differences and roles in disease.

PMID- 15581788
TI  - Anticipatory regulation and avoidance of catastrophe during exercise-induced
      hyperthermia.
AB  - Although evidence exists that a critical limiting temperature during exercise
      leads to premature fatigue secondary to a reduced central nervous system (CNS)
      drive to skeletal muscle, other thermoregulatory models may provide alternative
      explanations for limitations to exercise and heat stress in humans. This paper
      considers a number of mammalian species and their thermoregulatory strategies
      which deal with physical work and survival in hot environments. The critical
      limiting temperature hypothesis as the cause of premature fatigue is discussed in
      relation to the evidence for a CNS down-regulation of skeletal muscle drive.
      However, recent studies suggest that exercise duration or the point of fatigue is
      determined by a mechanism of anticipatory regulation for the avoidance of
      catastrophe. Evidence is offered that premature fatigue in the heat is not
      limited by a critical limiting temperature per se, but rather the rate at which
      core temperature rises so that the organism can anticipate the point of
      termination and avoid a catastrophic outcome.

PMID- 15581789
TI  - Characteristics of arylsulfatase in Russian sturgeon (Acipenser gueldenstaedti)
      semen.
AB  - Spermatozoa of sturgeons (Acipenseriformes), unlike teleosts, possess an
      acrosome. This paper provides data concerning biochemical characteristics of
      arylsulfatase (AS), an acrosomal enzyme, found in Russian sturgeon spermatozoa
      and seminal plasma. The enzymes were purified by a four-step procedure, using n
      butanol extraction, ion-exchange chromatography repeated twice and gel
      filtration. High purity of our enzymes was confirmed by silver staining
      electrophoresis and an immunological experiment. Kinetic parameters indicated
      that the purified enzymes belong to arylsulfatase type A. Similarity of the
      seminal plasma arylsulfatase to the spermatozoan enzyme showed us that
      arylsulfatase from seminal plasma might originate from damaged spermatozoa. The
      possible physiological consequences of the presence of arylsulfatase in Russian
      sturgeon semen are discussed.

PMID- 15581790
TI  - Seasonal variations in polyhydroxysteroids and related glycosides from digestive
      tissues of the starfish Patiria (=Asterina) pectinifera.
AB  - Seasonal variations in the concentrations of individual polyhydroxysteroids and
      related low molecular weight glycosides in pyloric caeca and stomach of the
      starfish Patiria (=Asterina) pectinifera collected at one location near
      Vladivostok have been studied. HPLC analysis on the fractions containing these
      substances showed a fairly constant composition of steroids in digestive tissues
      of P. pectinifera in spite of small seasonal variations in the relative
      concentrations of individual compounds.

PMID- 15581791
TI  - Chemical characterization of sialyl oligosaccharides in milk of the Japanese
      black bear, Ursus thibetanus japonicus.
AB  - Sialyl oligosaccharides were separated from two samples of Japanese black bear
      milk by extraction with chloroform/methanol, gel filtration on Bio Gel P-2, ion
      exchange chromatography on DEAE-Sephadex A-50 and high-performance liquid
      chromatography (HPLC) on a TSK gel Amido-80 column. They were characterized by
      (1)H-NMR spectroscopy. The structures of four sialyl oligosaccharides separated
      from the milk were the following: Neu5Ac(alpha2-3)Gal(beta1-4)Glc. Neu5Ac(alpha2
      6)Gal(beta1-4)GlcNAc(beta1-3)[Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1
      3)]GlcNAc(beta1-6)]Gal(beta1-4)Glc. Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1
      3)[Gal(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1
      6)]Gal(beta1-4)Glc. Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)[Neu5Ac(alpha2
      6)Gal(beta1-4)GlcNAc(beta1-6)Gal(beta1-4)Glc.

PMID- 15581792
TI  - Retinal is the essential form of retinoid for storage and transport in the adult
      of the ascidian Halocynthia roretzi.
AB  - Retinoids in the organs (gonad [GND], body wall muscle [BWM], hepatopancreas
      [HP], gill, hemolymph cells and hemolymph plasma) of the adult ascidian
      Halocynthia roretzi were analyzed by high performance liquid chromatography.
      Retinal (RAL) occurred in every organ examined, and most of RAL (>/=99%) was
      localized in the GND and BWM. None of the organs contained significant amounts of
      retinol (ROL) or retinyl ester (RE). Lipid droplets, which are characteristic of
      stellate cells (RE-storing cells of vertebrates), could not be found in the GND,
      BWM and HP by microscopic observations. These results indicate that this ascidian
      lacks the RE-storing mechanism, which is ubiquitous in adult vertebrates. The
      amount and localization of RAL showed the annual change in relation to the
      reproductive cycle. During summer, the growing season, RAL was present in both
      GND and BWM at a ratio of about 3:2. From summer to winter, RAL in the GND
      gradually increased, concomitant with the decrease of RAL in the BWM. In winter,
      the spawning season, most of RAL was present in the GND (ca. 98%). RAL appears to
      be accumulated first in the BWM and transported to oocytes accompanying yolk
      accumulation. ROL and RE were not implicated in the storage and transport of
      retinoids. The results in the present research strongly suggest that retinoic
      acid (RA) is produced by the two-step enzymatic reaction: carotenoid cleavage to
      RAL followed by RAL oxidation to RA and that the prevertebrate chordate lacks ROL
      metabolizing systems.

PMID- 15581793
TI  - Anti-adhesive glycoproteins in echinoderm mucus secretions.
AB  - Marine invertebrates produce a large variety of mucus secretions which are rich
      in glycoproteins. As part of our studies of natural antifouling mechanisms, mucus
      secretions from the starfish Marthasterias glacialis and Porania pulvillus and
      the brittlestar Ophiocomina nigra have been used to characterise the structure
      and function of some of the glycoproteins present in these secretions. Mucus was
      collected from all three species and fractionated by size exclusion
      chromatography. A high molecular weight glycoprotein fraction was collected from
      each species. Monosaccharide analysis and FTIR demonstrated a composition
      consistent with a mucin-type glycoprotein. The mucin from M. glacialis and O.
      nigra inhibited in vitro bacterial adhesion in a dose-dependent manner. In
      contrast, the mucin from P. pulvillus promoted bacterial adhesion in a dose
      dependent manner. All of the mucins inhibited the adhesion of human neutrophils
      to cultured human vascular endothelial cells (HUVECs) and had no anticoagulant
      activity. The mucins described here have adhesion-regulating functions that may
      have a role in the antifouling or feeding mechanisms of the organisms that
      produce them. These mucins may also be of therapeutic value through their ability
      to regulate human neutrophil adhesion or bacterial adhesion.

PMID- 15581794
TI  - Assessment of lipid and essential fatty acids requirements of black seabream
      (Spondyliosoma cantharus) by comparison of lipid composition in muscle and liver
      of wild and captive adult fish.
AB  - The primary aim of the present study was to compare the contents of total lipid,
      lipid classes and their associated fatty acids in muscle and liver of wild and
      one-year captive black seabream (Spondyliosoma cantharus) adults, in order to
      elucidate the lipid and fatty acids requirements of this fish species of
      potential interest for aquaculture. The total lipid contents (TL) of muscle and
      liver of the captive fish were 2.5-fold greater than those of the wild fish. In
      consequence, contents of triacylglycerols were much higher in tissues of the
      captive fish. Distribution of fatty acids in total lipids and lipid classes of
      muscle and liver was also different between both groups of fish. For instance,
      percentages of 20:4n-6, 20:5n-6 and 22:6n-3 were considerably higher in the wild
      fish, whereas 18:1, 20:1, and 22:1n-9 as well as 18:2n-6 and 20:5n-3 were more
      abundant in the captive fish. These results suggest that the lipid composition of
      the commercial diet supplied to the captive black seabream differed greatly from
      that of the diet consumed by the fish in the wild, which hypothetically contains
      the desirable composition for the lipid nutrition of this fish species. Despite
      the good growth and survival achieved by the black seabream after one year in
      captivity, the significant accumulation of lipids and the imbalance of essential
      fatty acids in their muscle and livers, together with the absence of spawning,
      suggest that future research on the lipid requirements of this omnivorous species
      is necessary in order to establish whether the administration of currently
      available aquaculture formulated feeds is adequate for good black seabream
      performance and reproduction.

PMID- 15581795
TI  - Sulfated glycosaminoglycans in two hematophagous arthropod vectors of Chagas
      disease, Triatoma brasiliensis and Rhodnius prolixus (Hemiptera: Reduviidae).
AB  - The characterization of sulfated glycosaminoglycans (GAGs) in hematophagous
      arthropod vectors in general has been limited, with the exception of the studies
      in the triatomine Rhodnius prolixus. Heparan sulfate (HS) and chondroitin sulfate
      (CS) were previously identified and structurally characterized in extracts of
      whole bodies of fourth instar larvae of R. prolixus. Recently, we showed the
      expression of these two sulfated GAGs in specific body tissues of adult males and
      females and in embryos of R. prolixus. In the present work, we identified and
      compared the sulfated GAG composition in specific tissues of adult insects and in
      embryos of another triatomine species, Triatoma brasiliensis. Sulfated GAGs were
      isolated from the fat body, intestinal tract, and the reproductive tracts of
      adult insects and from embryos. Only HS and CS were found in the tissues
      analyzed. The present results extend the initial observations on the sulfated GAG
      composition in R. prolixus by showing that these molecules are widely distributed
      among internal organs of triatomines. These observations may be useful for future
      investigations aiming to evaluate the possible implication of these compounds in
      physiological events that take place in a specific organ(s) in these insects.

PMID- 15581796
TI  - A novel serine protease complexed with alpha2-macroglobulin from skeletal muscle
      of lizard fish (Saurida undosquamis).
AB  - A novel fish muscle serine protease named muscle soluble serine protease (MSSP)
      was purified from the soluble fraction of lizard fish (Saurida undosquamis:
      Synodontidae) muscle by ammonium sulfate fractionation followed by four steps of
      column chromatographies. In native-PAGE, the purified enzyme appeared as a single
      band with an estimated mol. mass of approximately 380 kDa by gel filtration. In
      SDS-PAGE under reducing conditions, the purified enzyme migrated as two protein
      bands at 110 and 100 kDa, named subunits A and B, respectively. The 20 residues
      of N-terminal amino acid sequence of subunit B showed 70% of homology to beta
      chain of carp alpha(2)-macroglobulin-1. Moreover, both subunits A and B showed
      immunoreactivity with anti carp alpha(2)-macroglobulin antibody. Purified MSSP
      was inactivated by Pefabloc SC, aprotinin, benzamidine and TLCK, but not by
      alpha(1)-antitrypsin. After acid treatment (pH 2, 24 h), however, the enzyme
      activity eluted at 14 kDa from Sephacryl S-200 carried out under acidic
      conditions was inhibited by alpha(1)-antitrypsin. Lizard fish MSSP most rapidly
      hydrolyzed Boc-Val-Pro-Arg-MCA and Boc-Gln-Arg-Arg-MCA, but did not hydrolyzed
      Suc-Leu-Leu-Val-Tyr-MCA and Suc-Ala-Ala-Pro-Phe-MCA, and was not suppressed
      either by E-64, pepstatin A and ethylenediaminetetraacetic acid (EDTA). These
      results indicate that the purified MSSP is a serine protease complexed with
      alpha(2)-macroglobulin, and the entrapped protease was dissociated by the acid
      treatment. Purified and free MSSPs were most active at pH 10.0 and 9.0,
      respectively. Purified MSSP degraded myofibrillar proteins and casein but time
      courses of degradation of these substrates by the enzyme differed.

PMID- 15581797
TI  - Temperature-dependent expression patterns of grass carp fast skeletal myosin
      heavy chain genes.
AB  - Three types of myosin heavy chain cDNA clone named 10 degrees C, intermediate and
      30 degrees C types were isolated from fast skeletal muscles of thermally
      acclimated grass carp Ctenopharyngodon idellus. Three clones encompassing parts
      of 3'-translated and entire 3'-untranslated regions showed high heterogeneities
      in their nucleotide sequences in the 3'-untranslated region. The comparison in
      the deduced amino acid sequence of the 10 degrees C-type clone with those of the
      intermediate- and 30 degrees C-type clones showed 88% and 89% identities,
      respectively. By contrast, the deduced amino acid sequence of the intermediate
      type clone shared much higher identity of 97% with its 30 degrees C-type
      counterpart. Northern blot analysis demonstrated that the 10 degrees C- and 30
      degrees C-type clones were predominantly expressed in grass carp acclimated to 10
      and 30 degrees C, respectively. The intermediate type was expressed both in grass
      carp acclimated to 20 and 30 degrees C. Furthermore, expression patterns of the
      three myosin heavy chain genes were altered in accompaniment with seasonal
      temperature fluctuation. In autumn and winter grass carp expressed the 10 degrees
      C-type gene almost exclusively, whereas it was completely replaced by the
      intermediate- and 30 degrees C-type genes in spring and summer. These results
      suggest that tetraploid grass carp also undergo an adaptation to fluctuating
      environmental temperatures by selectively expressing fast skeletal myosin heavy
      chain isoforms as do diploid common carp previously reported.

PMID- 15581798
TI  - Effects of 3-thia fatty acids on feed intake, growth, tissue fatty acid
      composition, beta-oxidation and Na+,K+-ATPase activity in Atlantic salmon.
AB  - Atlantic salmon (Salmo salar) with an initial mass of 86 g were reared in 12
      degrees C seawater for 8 weeks to a final average mass of 250 g. The fish were
      fed fish meal and fish oil-based diet supplemented with either 0%, 0.3% or 0.6%
      of tetradecylthioacetic acid (TTA), a 3-thia fatty acid. The specific growth rate
      (SGR) decreased with increasing dietary dose of TTA. The SGR of the group fed 0%
      of TTA (Control) was 1.8; that of the group fed 0.3% of TTA (TTA-L) was 1.7, and
      that of the group fed 0.6% of TTA (TTA-H) was 1.5. The mortality increased with
      increased dietary dose of TTA. The mitochondrial beta-oxidation capacity in the
      liver of fish fed the TTA diets was 1.5 to 2 times higher than that of the
      Control fish. TTA supplementation caused substantial changes in the fatty acid
      compositions of the phospholipids (PL), triacylglycerols (TAG) and free fatty
      acids (FFA) of gills, heart and liver. The percentages of n-3 fatty acids,
      particularly 22:6 n-3, increased in fish fed diets containing TTA, while the
      percentage of the saturated FAs 14:0 and 16:0 in the PL fractions of the gills
      and heart decreased. The sum of monounsaturated FAs in the PL and TAG fractions
      from liver was significantly higher in fish fed diets containing TTA. TTA itself
      was primarily incorporated into PL. Two catabolic products of TTA (sulphoxides of
      TTA) were identified, and these products were particularly abundant in the
      kidney. TTA supplementation had no significant effect on the activity of the
      membrane-bound enzyme Na(+),K(+)-ATPase.

PMID- 15581799
TI  - Cloning and characterization of an mRNA encoding a novel G protein alpha-subunit
      abundant in mantle and gill of pearl oyster Pinctada fucata.
AB  - Nacre formation is an ideal model to study biomineralization processes. Although
      much has been done about biomineralization mechanism of nacre, little is known as
      to how cellular signaling regulates this process. We are interested in whether G
      protein signaling plays a role in mineralization. Degenerate primers against
      conserved amino acid regions of G proteins were employed to amplify cDNA from the
      pearl oyster Pinctada fucata. As a result, the cDNA encoding a novel G(s)alpha
      (pfG(s)alpha) from the pearl oyster was isolated. The G(s)alpha cDNA encodes a
      polypeptide of 377 amino acid residues, which shares high similarity to the
      octopus (Octopus vulgaris) G(s)alpha. The well-conserved A, C, G (switch I),
      switch II functional domains and the carboxyl terminus that is a critical site
      for interaction with receptors are completely identical to those from other
      mollusks. However, pfG(s)alpha has a unique amino acid sequence, which encodes
      switch III and interaction sites of adenylyl cyclase respectively. In situ
      hybridization and Northern blotting analysis revealed that the oyster G(s)alpha
      mRNA is widely expressed in a variety of tissues, with highest levels in the
      outer fold of mantle and epithelia of gill, the regions essential for
      biomineralization. We also show that overexpression of the pfG(s)alpha in
      mammalian MC3T3-E1 cells resulted in increased cAMP levels. Mutant pfG(s)alpha
      that has impaired CTX substrate diminished its ability to induce cAMP production.
      Furthermore, the alkaline phosphatase (ALP) activity, an indicator for
      mineralization, is induced by the G(s)alpha in MC3T3-E1 cells. These results
      indicated that G(s)alpha may be involved in regulation of physiological function,
      particularly in biological biomineralization.

PMID- 15581800
TI  - Molecular cloning and expression analysis of phospholipase Cdelta from mud loach,
      Misgurnus mizolepis.
AB  - A gene encoding phosphoinositide-specific phospholipase C (PLC), designated ML
      PLCdelta, was cloned from mud loach (Misgurnus mizolepis) liver. A complete cDNA
      encoding ML-PLCdelta was isolated by screening the cDNA library of mud loach
      liver and using the 5'-rapid amplification of cDNA ends (RACE) method. The full
      length ML-PLCdelta gene contains an open reading frame of 2325 base pairs
      encoding a 774 amino acid protein with a molecular mass of 88,072 Da; this
      corresponds to the size of the protein expressed in Escherichia coli BL21 (DE3)
      using pET28a vector. It contains all of the characteristic domains found in
      mammalian PLCdelta isozymes (PH domain, EF-hands, X-Y catalytic region, and a C2
      domain). A homology search revealed that ML-PLCdelta shares relatively high
      sequence identity with mammalian PLCdelta1 (51-52%) and catfish PLCdelta (64%).
      The recombinant ML-PLCdelta protein expressed as a histidine-tagged fusion
      protein in E. coli was purified to apparent homogeneity by Ni(2+)-NTA affinity
      chromatography. The recombinant ML-PLCdelta showed a concentration-dependent PLC
      activity to phosphatidylinositol 4,5-bis-phosphate (PIP(2)) and its activity was
      Ca(2+)-dependent, which was similar to mammalian PLCdelta isozymes.

PMID- 15581801
TI  - Microvascular and biochemical compensation during ventricular hypertrophy in male
      rainbow trout.
AB  - We investigated whether there are compensatory changes in the coronary
      microvasculature, cardiac lipid metabolism, and myocyte ultrastructure associated
      with ventricular enlargement in male rainbow trout. Epicardial tissue was sampled
      at different stages of sexual maturation, and we estimated arterial capillary
      density, intercapillary diffusion distance, and applied a diffusion model to
      predict PO(2) at different workloads. We also measured biochemical indices of
      lipid metabolism and estimated fractional volumes of mitochondria and myofibrils
      in myocytes. Immature fish with nonenlarged ventricles had the highest capillary
      length densities (1620+/-158 mm mm(-3)). Maturing trout with moderate ventricular
      hypertrophy had lower capillary length densities (1103+/-58 mm mm(-3)) and
      similar diffusion distances (13.9+/-0.7 microm) compared with immature fish
      (11.7+/-0.9 microm). The largest ventricles had intermediate capillary length
      densities (1457+/-288 mm mm(-3)) and diffusion distances (12.8+/-0.8 microm).
      Modelling predicted that enlarged ventricles would not become anoxic even at
      maximal workloads. Biochemical markers of fatty acid metabolism and aerobic
      capacity were unchanged with hypertrophy. Volume densities of mitochondria and
      myofibrils were also not influenced by cardiac growth. In summary, ventricle
      hypertrophy results in expansion of the coronary capillary bed and the
      maintenance of the epicardial capacities for fat and oxidative metabolism.

PMID- 15581802
TI  - Fatty acid composition of aquatic insect larvae Stictochironomus pictulus
      (Diptera: Chironomidae): evidence of feeding upon methanotrophic bacteria.
AB  - Larvae of the chironomid Stictochironomus pictulus were collected from Lake Biwa,
      central Japan. Both the fatty acid composition of the total lipid fraction and
      the carbon stable isotope ratios of whole larvae were determined. Larvae showed
      delta(13)C values of -57.4 per thousand to -62.4 per thousand, similar to the
      values of methane recorded from the lake sediments. A high level of
      monounsaturated fatty acids (MUFAs; approximately 50% of total fatty acids) and
      an extremely low level of n-3 series polyunsaturated fatty acids (PUFAs) in the
      total lipids of S. pictulus indicated a predominantly bacterial nutrition for
      this species. Moreover, chironomid tissues contained large amounts of the Type I
      methanotroph group-specific fatty acid, 16:1(n-8) (approximately 8% of total
      fatty acids). This is the first time such a fatty acid biomarker has been
      described from freshwater invertebrates. The data suggest that S. pictulus larvae
      directly feed upon methanotrophic bacteria.

PMID- 15581803
TI  - ATP and ADP hydrolysis in the kidney and liver of fish, chickens and rats.
AB  - We investigated NTPDase-like activity [ecto-nucleoside triphosphate
      diphosphohydrolases (E-NTPDases)] in liver and kidney membrane from silver
      catfish (Rhamdia quelen), chicken (Gallus gallus) and rat (Rattus norvegicus)
      under different conditions and in the presence of several inhibitors. The cation
      concentration required for maximal activity was 0.5, 1.5 and 2.0 mM for fish,
      chicken and rat liver, respectively (with ATP and ADP as substrates). The maximal
      activity in the kidney was observed at calcium concentrations of 0.5, 2.0, 1.5 mM
      (ATP) and 0.5, 1.5, 1.0 (ADP) for fish, chickens and rats, respectively. The
      results showed that the pH optimum for all animals and for the two tissues was
      close to 8.0. The temperature chosen was 25 degrees C for fish and 36 degrees C
      for chicken and rat preparations. Ouabain had no effect on the NTPDase-like
      activity of fish, chickens or rats. NTPDase activity was decreased in the
      presence of lanthanum in the chicken (ADP) and rat (ATP and ADP) liver. In the
      kidney, lanthanum inhibited fish ATP and rat ATP and ADP (0.2 mM) hydrolysis. N
      ethylmaleimide (NEM) had an inhibitory effect on the kidney of all species at the
      concentration of 3.0 mM (ADP). Orthovanadate only inhibited fish membrane
      NTPDase; azide only inhibited the preparation at high concentrations (10 mM) and
      fluoride inhibited it at 10 mM (fish and chicken) and 5 mM (rat). Trifluoperazine
      (0.05-0.2 mM) and suramin (0.03-0.3 mM) inhibited NTPDase at all concentrations
      tested. These results suggest that NTPDase-like activity shows a different
      behavior among the vertebrate species and tissues studied. Additionally, we
      propose that NTPDase1 is the main enzyme present in this preparation.

PMID- 15581804
TI  - Differential susceptibility to oxidative stress of two scleractinian corals:
      antioxidant functioning of mycosporine-glycine.
AB  - This study examined the importance of mycosporine-glycine (Myc-Gly) as a
      functional antioxidant in the thermal-stress susceptibility of two scleractinian
      corals, Platygyra ryukyuensis and Stylophora pistillata. Photochemical efficiency
      of PSII (F(v)/F(m)), activity of antioxidant enzymes, superoxide dismutase (SOD)
      and catalase (CAT), and composition and abundance of mycosporine-like amino acids
      (MAAs) in the coral tissue and in symbiotic zooxanthellae were analyzed during 12
      h exposure to high temperature (33 degrees C). After 6- and 12-h exposures at 33
      degrees C, S. pistillata showed a significantly more pronounced decline in
      F(v)/F(m) compared to P. ryukyuensis. A 6-h exposure at 33 degrees C induced a
      significant increase in the activities of SOD and CAT in both host and
      zooxanthellae components of S. pistillata while in P. ryukyuensis a significant
      increase was observed only in the CAT activity of zooxanthellae. After 12-h
      exposure, the SOD activity of P. ryukyuensis was unaffected in the coral tissue
      but slightly increased in zooxanthellae, whereas the CAT activity in the coral
      tissue showed a 2.5-fold increase. The total activity of antioxidant enzymes was
      significantly higher in S. pistillata than in P. ryukyuensis, suggesting that P.
      ryukyuensis is less sensitive to oxidative stress than S. pistillata. This
      differential susceptibility of the corals is consistent with a 20-fold higher
      initial concentration of Myc-Gly in P. ryukyuensis compared to S. pistillata. In
      the coral tissue and zooxanthellae of both species investigated, the first 6 h of
      exposure to thermal stress induced a pronounced reduction in the abundance of Myc
      Gly but not in other MAAs. When exposure was prolonged to 12 h, the Myc-Gly pool
      continued to decrease in P. ryukyuensis and was completely depleted in S.
      pistillata. The delay in the onset of oxidative stress in P. ryukyuensis and the
      dramatic increase in the activities of the antioxidant enzymes in S. pistillata,
      which contains low concentrations of Myc-Gly suggest that Myc-Gly provides rapid
      protection against oxidative stress before the antioxidant enzymes are induced.
      These findings strongly suggest that Myc-Gly is functioning as a biological
      antioxidant in the coral tissue and zooxanthellae and demonstrate its importance
      in the survival of reef-building corals under thermal stress.

PMID- 15581805
TI  - Phospholipase A2 in cnidaria.
AB  - Phospholipase A2 (PLA2) is an enzyme present in snake and other venoms and body
      fluids. We measured PLA2 catalytic activity in tissue homogenates of 22 species
      representing the classes Anthozoa, Hydrozoa, Scyphozoa and Cubozoa of the phylum
      Cnidaria. High PLA2 levels were found in the hydrozoan fire coral Millepora sp.
      (median 735 U/g protein) and the stony coral Pocillopora damicornis (693 U/g)
      that cause skin irritation upon contact. High levels of PLA2 activity were also
      found in the acontia of the sea anemone Adamsia carciniopados (293 U/g). Acontia
      are long threads containing nematocysts and are used in defense and aggression by
      the animal. Tentacles of scyphozoan and cubozoan species had high PLA2 activity
      levels: those of the multitentacled box jellyfish Chironex fleckeri contained 184
      U/g PLA2 activity. The functions of cnidarian PLA2 may include roles in the
      capture and digestion of prey and defense of the animal. The current observations
      support the idea that cnidarian PLA2 may participate in the sting site irritation
      and systemic envenomation syndrome resulting from contact with cnidarians.

PMID- 15581806
TI  - Oxidative stress induced by corticosterone administration in broiler chickens
      (Gallus gallus domesticus) 1. Chronic exposure.
AB  - The effects of long-term dietary administration of corticosterone (CORT) on the
      induction of oxidative injury in broiler chickens (Gallus gallus domesticus) were
      evaluated. The experimental broiler chickens were fed with a diet supplemented
      with 30 mg CORT/kg diet for 2 weeks from 14 days of age onwards, while control
      chickens continued to consume the control diet. The growth performance parameters
      were recorded weekly, and a blood sample was obtained from eight birds of both
      groups before CORT administration and at 3, 7 and 14 days after treatment. The
      results showed that chronic CORT administration resulted in enhanced proteolysis
      and gluconeogenesis. Furthermore, CORT administration may initially induce the
      formation of reactive oxygen species (ROS) as indirectly reflected by an increase
      in lipid peroxidation. However, the significantly increased plasma uric acid (UA)
      and ceruloplasmin (CP) levels after 3 days of treatment indicates an enhancement
      of the nonenzymatic antioxidant capacity during stress, and in this way, the
      development of a more severe oxidative injury is alleviated. Broiler chickens
      seem to adapt to high circulating CORT levels in terms of their redox homeostasis
      after 3 days of treatment under the present experimental conditions.

PMID- 15581807
TI  - Oxidative stress induced by corticosterone administration in broiler chickens
      (Gallus gallus domesticus) 2. Short-term effect.
AB  - Two trials were conducted to evaluate the effects of short-term administration of
      corticosterone (CORT) on the induction of oxidative injury in broiler chickens
      (Gallus gallus domesticus). Twelve broiler chickens of 30 and of 40 days of age
      were respectively employed in Trial 1 and 2. Half of the chickens were
      administered subcutaneously with CORT (4 mg/kg body weight [BW] in corn oil),
      while another half served as controls (corn oil) in each trail. In Trial 1, a
      blood sample was obtained from each chicken immediately before administration and
      at 1 and 3 h after injection. In Trial 2, the liver and heart were obtained after
      3 h of CORT exposure. Short-term administration of CORT resulted in enhanced
      proteolysis and gluconeogenesis. There were no obvious changes in lipid
      peroxidation status of the heart and liver, whereas a decrease in lipid
      peroxidation in the plasma was observed after acute CORT exposure. The
      significantly increased plasma nonenzymatic antioxidants (uric acid [UA] and
      total antioxidant capacity) in concert with the enhanced enzymatic antioxidant
      activity (SOD in heart) during short-term CORT administration indicate preventive
      changes to counteract the oxidative injury, and these may be tissue specific.

PMID- 15581808
TI  - Hormonal control of a metamorphosis-specific transcriptional factor Broad-Complex
      in silkworm.
AB  - Insect metamorphosis is induced by the steroid 20-hydroxyecdysone (20E) in the
      absence of sesquiterpenoid juvenile hormone (JH). In Drosophila melanogaster, the
      Broad-Complex (BR-C) transcriptional factor plays critical roles during
      metamorphosis. We isolated cDNAs encoding BR-C in the silkworm Bombyx mori and
      examined their mRNA expression. cDNAs for three BR-C isoforms with zinc finger
      pairs (Z1, Z2 and Z4) and four isoforms lacking them were cloned. Their mRNAs
      were expressed in multiple tissues at the larval-pupal metamorphosis. In the
      anterior silk gland, BR-C mRNAs were expressed at the end of the last larval
      instar but not expressed during the penultimate instar. 20E administration
      induced BR-C mRNA expression and JH suppressed 20E-induced BR-C expression in
      this tissue both in vivo and in vitro. Thus, BR-C mRNAs are inducible by 20E only
      in the absence of JH, a finding that explains their metamorphosis-specific
      expression.

PMID- 15581809
TI  - An approach for contour detection of human kidneys from ultrasound images using
      Markov random fields and active contours.
AB  - In this paper, a novel method for the boundary detection of human kidneys from
      three dimensional (3D) ultrasound (US) is proposed. The inherent difficulty of
      interpretation of such images, even by a trained expert, makes the problem
      unsuitable for classical methods. The method here proposed finds the kidney
      contours in each slice. It is a probabilistic Bayesian method. The prior defines
      a Markov field of deformations and imposes the restriction of contour smoothness.
      The likelihood function imposes a probabilistic behavior to the data, conditioned
      to the contour position. This second function, which is also Markov, uses an
      empirical model of distribution of the echographical data and a function of the
      gradient of the data. The model finally includes, as a volumetric extension of
      the prior, a term that forces smoothness along the depth coordinate. The
      experiments that have been carried out on echographies from real patients
      validate the model here proposed. A sensitivity analysis of the model parameters
      has also been carried out.

PMID- 15581810
TI  - Confhusius: a robust and fully automatic calibration method for 3D freehand
      ultrasound.
AB  - This paper describes a new robust and fully automatic method for calibration of
      three-dimensional (3D) freehand ultrasound called Confhusius (CalibratiON for
      FreeHand UltraSound Imaging USage). 3D Freehand ultrasound consists in mounting a
      position sensor on a standard probe. The echographic B-scans can be localized in
      3D and compounded into a volume. However, especially for quantitative use, this
      process dramatically requires a calibration procedure that determines its
      accuracy and usefulness. Calibration aims at determining the transformation
      (translations, rotations, scaling) between the coordinates system of the
      echographic images and the coordinate system of the localization system. To
      calibrate, we acquire images of a phantom whose 3D geometrical properties are
      known. We propose a robust and fully automatic calibration method based on the
      Hough transform and robust estimators. Experiments have been done with synthetic
      and real sequences, and this calibration method is shown to be easy to perform,
      accurate, automatic and fast enough for clinical use.

PMID- 15581811
TI  - Analyzing attributes of vessel populations.
AB  - Almost all diseases affect blood vessel attributes (vessel number, radius,
      tortuosity, and branching pattern). Quantitative measurement of vessel attributes
      over relevant vessel populations could thus provide an important means of
      diagnosing and staging disease. Unfortunately, little is known about the
      statistical properties of vessel attributes. In particular, it is unclear whether
      vessel attributes fit a Gaussian distribution, how dependent these values are
      upon anatomical location, and how best to represent the attribute values of the
      multiple vessels comprising a population of interest in a single patient. The
      purpose of this report is to explore the distributions of several vessel
      attributes over vessel populations located in different parts of the head. In 13
      healthy subjects, we extract vessels from MRA data, define vessel trees
      comprising the anterior cerebral, right and left middle cerebral, and posterior
      cerebral circulations, and, for each of these four populations, analyze the
      vessel number, average radius, branching frequency, and tortuosity. For the
      parameters analyzed, we conclude that statistical methods employing summary
      measures for each attribute within each region of interest for each patient are
      preferable to methods that deal with individual vessels, that the distributions
      of the summary measures are indeed Gaussian, and that attribute values may differ
      by anatomical location. These results should be useful in designing studies that
      compare patients with suspected disease to a database of healthy subjects and are
      relevant to groups interested in atlas formation and in the statistics of tubular
      objects.

PMID- 15581812
TI  - Spatiotemporal clustering of fMRI time series in the spectral domain.
AB  - We propose a new method for the analysis of functional magnetic resonance images
      (fMRI). The decision that a voxel v0 is activated is based not solely on the
      value of the fMRI signal at v0, but rather on the comparison of all time series
      s(v)(t) in a small neighborhood Nv0 around v0. Our approach explicitly takes into
      account the intrinsic spatiotemporal correlations that exist in the data. We
      focus on experimental designs with periodic stimuli, and therefore we can capture
      most of the features of the BOLD signal with a low dimensional subspace in the
      frequency domain. The presence of activated time series can be detected by
      partitioning the time series in this low dimensional space. Experiments with
      simulated data, and experimental fMRI data, demonstrate that our approach can
      outperform standard methods of analysis, such as the t-test.

PMID- 15581813
TI  - Detection and analysis of statistical differences in anatomical shape.
AB  - We present a computational framework for image-based analysis and interpretation
      of statistical differences in anatomical shape between populations. Applications
      of such analysis include understanding developmental and anatomical aspects of
      disorders when comparing patients versus normal controls, studying morphological
      changes caused by aging, or even differences in normal anatomy, for example,
      differences between genders. Once a quantitative description of organ shape is
      extracted from input images, the problem of identifying differences between the
      two groups can be reduced to one of the classical questions in machine learning
      of constructing a classifier function for assigning new examples to one of the
      two groups while making as few misclassifications as possible. The resulting
      classifier must be interpreted in terms of shape differences between the two
      groups back in the image domain. We demonstrate a novel approach to such
      interpretation that allows us to argue about the identified shape differences in
      anatomically meaningful terms of organ deformation. Given a classifier function
      in the feature space, we derive a deformation that corresponds to the differences
      between the two classes while ignoring shape variability within each class. Based
      on this approach, we present a system for statistical shape analysis using
      distance transforms for shape representation and the support vector machines
      learning algorithm for the optimal classifier estimation and demonstrate it on
      artificially generated data sets, as well as real medical studies.

PMID- 15581814
TI  - 4D deformable models with temporal constraints: application to 4D cardiac image
      segmentation.
AB  - Segmentation of time series of 3D cardiac images is clinically used for the
      assessment of the mechanical function of the left ventricle. To take into account
      the 4D (3D+T) nature of those images, we propose to extend the deformable surface
      framework by introducing time-dependent constraints. Thus, in addition to
      computing an internal force for enforcing the regularity of the deformable model,
      prior motion knowledge is introduced in the deformation process through either
      temporal smoothing or trajectory constraints. In this paper, deformable surfaces
      are represented as simplex meshes owing to their generality and their ability to
      compute mean curvature at each vertex. The segmentation accuracy of this 4D
      deformable model is estimated on synthetic SPECT image sequences for which a
      ground truth about the LV volume is known. Segmentation of non-synthetic SPECT
      and other modalities 4D images is also discussed.

PMID- 15581815
TI  - [Taylor method: antiquity or reality].

PMID- 15581816
TI  - [Endocrine tumors of the gastro-intestinal tract (Carcinoid tumors)].
AB  - Surgical management of gastro-intestinal endocrine tumors has to be adapted to
      tumor localization and disease extension (local and general). The aim of this
      literature review was to define surgical management of these unfrequent tumors.

PMID- 15581817
TI  - [Morbidity after stapled haemorrhoidectomy: long-term results about 140 patients
      and review of the literature].
AB  - AIM: The aim of this study was to determine the results and the complications of
      the treatment of hemorrhoids with circular stapler with a follow-up of 18 months,
      and to review the complications in the literature. METHODS: From April 1998 to
      August 1999, 140 patients (83 males and 57 females) with an average age of 43.8
      years (range: 19-83 years) underwent haemorrhoidectomy using a circular stapler
      in three university hospital centers. The degree of hemorrhoids has been
      classified: three cases of degree II, 97 cases of degree III, and 40 cases of
      degree IV. All the patients were prospectively evaluated at two weeks, two and 18
      months after surgery. RESULTS: The average length of the operation was 18 minutes
      (range: 8-60 minutes). Mean hospital stay was 36 hours (range: 8-72 hours). There
      was no intraoperative complication. There was no mortality. The postoperative
      complication rate was 7.8% (N = 11): there were five cases of bleeding that two
      complicated by a submucosal hematoma (one was infected and needed a rectotomy on
      day 21), two cases of urinary retention, and two cases of external hemorrhoid
      thrombosis. The bleeding occurred in the 12 hours after surgery except for one
      patient with antivitamin K whith presented a secondary bleeding on day 16. At 18
      months, five patients presented a moderate asymptomatic stricture dilated on
      digital examination. Two patients complained of persistent skin tags. Neither
      functional trouble nor incontinence to gas, liquids, or solids was presented.
      With a mean follow-up of 40 months, 90% (N = 112) of the patients were fully
      satisfied. CONCLUSIONS: Treatment of hemorrhoids with circular stapler appears to
      be effective with 96% of patients fully satisfied at 18 months. The morbidity
      rate was low, and no higher than the diathermy excision hemorrhoidectomy. The
      results are directly dependent on the practice that required a learning, and not
      on the technique itself.

PMID- 15581818
TI  - [Non operative treatment for perforated peptic ulcer: results of a prospective
      study].
AB  - BACKGROUND: The conservative management of perforated peptic ulcer has not gained
      widespread acceptance despite introduction of proton-pomp inhibitors because
      surgical procedures can achieve immediate closure by eventually using a
      laparoscopic approach. The aim of this prospective study was to evaluate the
      results of Taylor's method and to identify predictive factors of failure of
      medical treatment in patients presenting with perforated peptic ulcer. METHOD:
      Between 1990 and 2000, 82 consecutive patients, with diagnosis of perforated
      peptic ulcer were prospectively included in this study. They were initially
      treated with non-operative procedure (nasogastric suction and intravenous
      administration of H2-blockers or proton-pomp inhibitors). No clinical improvement
      after 24 hours required a surgical treatment. Predictive factors of failure of
      non-operative treatment were tested in univariate or multivariate analysis.
      RESULTS: Clinical improvement was obtained with non-operative treatment in 54% of
      the patients (44/82). The overall mortality rate was 1%. In univariate analysis,
      significant predictive factors of failure of non-operative treatment were: size
      of pneumoperitoneum, heart beat >94 bpm, abdominal meteorism, pain at digital
      rectal exam, and age >59 years. In multivariate analysis, the significant factors
      were the size of pneumoperitoneum, heart beat, and abdominal meteorism. The
      association of these criteria: size of pneumoperitoneum >size of the first lumbar
      vertebra, heart beat >94 bpm, pain at digital rectal exam and age > 59 years ,
      led to surgical treatment in all cases. CONCLUSION: These results suggest that
      more than 50% of patients with perforated peptic ulcer respond to conservative
      treatment without surgery and that the association of few criteria (size of
      pneumoperitoneum, heart beat, pain at digital rectal exam and age) require
      emergency surgery.

PMID- 15581819
TI  - [Results of surgical resection of squamous cells carcinoma of the oesophagus with
      or without preoperative radiochemotherapy: comparative and retrospective study].
AB  - AIM OF THE STUDY: The aim of the study was to assess preoperative radio
      chemotherapy for squamous cell carcinoma of the esophagus. MATERIAL AND METHODS:
      This study was a retrospective comparison between radio-chemotherapy followed by
      surgical resection (RCPO) and surgery alone. The RCPO group included patients
      with tumor located in the middle or lower third of the esophagus, staged T2 or T3
      tumors without distant metastases by pretherapeutic assessment. These patients
      were matched with patients who underwent immediate surgery, who constituted the
      surgical group (CHIR). Both groups were matched for gender, age, tumor
      localization (middle or lower third), T stage, and surgical procedure. Each group
      included 77 men and 9 women, 50 tumors of the middle third and 36 of the lower
      third of the oesophagus, and 19 tumors T2 and 67 T3 ones. RESULTS: Morbidity of
      both groups was not significantly different. The mortality was 4% in the group
      CHIR and 12% in the group RCPO (P =0.07). The rate of radical resection (R0) was
      significantly higher in the RCPO group (74% vs. 51%; P =0.001). The overall 5
      year survival rate was 38% after R0 surgery and 11% after R1 or R2 surgery (P
      <0.0001). After R0 surgery, the 5-year survival rate was 47% in the CHIR group
      and 32% in the RCPO group (P =0.06). CONCLUSION: Preoperative radiochemotherapy
      increases the rate of radical surgical resection without significant increase in
      postoperative morbidity and mortality.

PMID- 15581820
TI  - [Surgical treatment of pulmonary metastases of colorectal cancer. Do the
      indications evolved?].
AB  - AIM OF THE STUDY: The aim of this study was to evaluate a single-institution
      experience in the surgical treatment of lung metastases from colorectal cancer.
      PATIENTS AND METHODS: During a 16 years period, 42 patients underwent lung
      metastasectomy at the University Hospital of Nice for a total of 57 surgical
      interventions. Data were retrospectively collected and analysed in term of
      prognostic factors and long-term survival. RESULTS: The mean age was 64.5 years
      and there were 26 males and 16 females. In 36 cases lung metastasis were
      metachronous and the disease-free mean interval was 28.7 months. Eighteen
      patients had bilateral disease. In ten patients hepatic metastasectomy was done
      before lung resection. Forty-seven operations were performed for the 1(st)
      episode of lung metastasis (1 bilobectomy, 21 lobectomy, 4 segmentectomy and 38
      wedge resections). Mediastinal metastatic disease was present in six patients. No
      patient died and the postoperative morbidity was 6.25%. Six patients needed
      operation for recurrent disease. Two patients died after completion
      pneumonectomy. Overall five and ten-year survival were 29.5 respectively 26.2%.
      The log-rank test identified two significant prognostic factors: radicality of
      metastasectomy (P =0.0066) and a disease-free interval longer than two years (P=
      0.0021). CONCLUSION: Our study suggests that local control of lung metastasis can
      improve survival only when a radical resection can be achieved. Selection
      criteria need to be improved in order to avoid unnecessary lung resection in
      patients with high risk of recurrences. The Pet-scan should probably have a
      certain interest in selecting these patients.

PMID- 15581821
TI  - [Should patients with acute severe pancreatitis be given antibiotic
      prophylaxis?].

PMID- 15581822
TI  - [Crohn's disease with anoperineal lesions: use of MRI].
AB  - The authors report a case of perineal Crohn disease with three anal fissures.
      Because of a persistant fever without any clinical aspect of abscess they
      practiced MRI examination that discovered an abscess of the recto-vaginal wall.
      The patient was operated under general anaesthesia. This clinical case shows the
      interest of radiologic exams, particularly pelvic MRI for the precise lesional
      diagnosis of anoperineal lesions of Crohn's disease, that is still complex and
      difficult to treat.

PMID- 15581823
TI  - [Transhepatic percutaneous embolisation of a post-traumatic pseudoaneurysm of
      hepatic artery].
AB  - Pseudoaneurysm of the hepatic artery is a rare complication of blunt abdominal
      trauma. We report a case of post-traumatic pseudoaneurysm diagnosed several
      months after the initial traumatism in a 18-year-old man who presented recurrent
      abdominal pain. This pseudoaneurysm was successfully treated by association of
      both classical endovascular treatment and transhepatic percutaneous embolization.

PMID- 15581824
TI  - [Carcinoid tumor from the small bowel].
AB  - Carcinoid tumors are non-pancreatic digestive neuroendocrine tumors well
      differentiated. Most of time they are developed from enterochromaffin cells of
      the digestive tract. Most of them are localized in ileum, rectum, stomach and
      appendix. Only bronchi are a frequent extra-digestive localization (20 to 25%).
      Most of these tumors are asymptomatic and discovered incidentally during a
      laparotomy or secondary to the exploration of a carcinoid syndrome. From a case
      report and a recent review of literature, diagnosis, histology and treatment of
      small bowel carcinoid tumors are summarized.

PMID- 15581825
TI  - [Conventional surgical treatment of anal fistulas].
AB  - Conventional treatment of anal fistulas depends from anatomical relationships of
      the fistula with striated sphincter complex. Location of primary opening is
      crucial, blind fistula does not exist. Low fistulas can be treated in a single
      procedure without remarkable consequence on continence. Anterior fistulas in
      female, multiparas and multioperated patients with impaired continence must be
      treated with caution with at least two stages. High anal fistulas will always be
      treated in several stages: first stage is drainage with a loose seton during two
      or three months followed by fistulotomy or cutting seton.

PMID- 15581826
TI  - [Renew of general surgery teaching in Kampuchea. Unique experiment or model?].

PMID- 15581827
TI  - [Digest of articles published in the ANZ J. Surg. 2003, volume 73].

PMID- 15581828
TI  - [The epic story of Dominique Larrey (1766-1842). Military Surgeon - Baron of
      First Empire].

PMID- 15581829
TI  - Prevalence of C282Y and H63D mutations in the haemochromatosis (HFE) gene in
      Tunisian population.
AB  - The studies of the HFE mutations: H63D and C282Y in North African populations
      have revealed the extreme rarity or even the absence of the C282Y mutation. We
      have examined 1140 chromosomes (570 Tunisian people) for the presence of the two
      HFE mutations by PCR-RFLP analysis. We have found that the allele frequencies
      are, respectively, 15.17% (+/-2.1%) for the H63D and 0.09% (+/-0.17%) for the
      C282Y. These results are consistent with the worldwide spread of the H63D
      mutation and the north European restriction of the C282Y. This study will be
      completed by determining whether homozygote trait for H63D and associated risk
      factors (beta thalassemia) can lead to iron overload in Tunisia.

PMID- 15581830
TI  - Y chromosome micro-deletions in idiopathic infertility from Northern India.
AB  - Azoospermia factor locus (AZF) is assumed to contain the genes responsible for
      spermatogenesis. Deletions in these genes are thought to be pathologically
      involved in some cases of male infertility associated with azoospermia or
      oligozoospermia. An attempt was made to establish the prevalence of micro
      deletions on the Y chromosome in 79 infertile North Indians with azoospermia and
      oligozoospermia. Detail clinical examinations as well as endocrinological
      parameters were also done. Polymerase chain reaction (PCR) micro-deletion
      analysis was done in 79 infertile men. For this, genomic DNA was extracted from
      the peripheral blood. Seven sets of primers were used encompassing AZFa, AZFb and
      AZFc regions. Micro-deletions in five of the 79 cases (6.3%) showed deletions of
      at least one of the STS markers. Deletions were detected with known and unknown
      aetiology and at least in one of the infertile male with varicocele. AZF micro
      deletions seen in idiopathic infertile males suggest the need for molecular
      screening in non-idiopathic cases.

PMID- 15581831
TI  - DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a
      Mexican ethnic group.
AB  - Type 2 diabetes mellitus is a complex metabolic disorder resulting from the
      action and interaction of many genetic and environmental factors. It has been
      reported that polymorphisms in genes involved in the metabolism of glucose are
      associated with the susceptibility to develop type 2 diabetes mellitus. Although
      the risk of developing type 2 diabetes mellitus increases with age, as well as
      with obesity and hypertension, its prevalence and incidence are different among
      geographical regions and ethnic groups. In Mexico, a higher prevalence and
      incidence has been described in the south of the country, and differences between
      urban and rural communities have been observed. We studied 73 individuals from
      Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This
      population has shown a high prevalence of type 2 diabetes mellitus, and the aim
      of this study was to analyze the relationship between the Pst I (insulin gene),
      Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene)
      polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this
      population. Clinical evaluation consisted of BMI and blood pressure measurements,
      and biochemical assays consisted of determination of fasting plasma insulin and
      glucose levels. PCR and restriction enzyme digestion analysis were applied to
      genomic DNA to identify the three polymorphisms. From statistical analysis
      carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were
      not associated with the type 2 diabetes, obese or hypertensive phenotypes in this
      population. Nevertheless, there was an association between the Nsi I and Pst I
      polymorphisms and increased serum insulin levels.

PMID- 15581832
TI  - The peptide nucleic acids (PNAs): a new generation of probes for genetic and
      cytogenetic analyses.
AB  - Peptide nucleic acids (PNAs) are synthetic homologs of nucleic acids in which the
      phosphate-sugar polynucleotide backbone is replaced by a flexible pseudo-peptide
      polymer to which the nucleobases are linked. This structure gives PNAs the
      capacity to hybridize with high affinity and specificity to complementary
      sequences of DNA and RNA, and also confers remarkable resistance to DNAses and
      proteinases. The unique physico-chemical characteristics of PNAs have led to the
      development of a wide range of biological assays. Several exciting new
      applications of PNA technology have been published recently in genetics and
      cytogenetics. Also, PNA-based hybridization technology is developing rapidly
      within the field of in situ fluorescence hybridization, pointing out the great
      potential of PNA probes for chromosomal investigations.

PMID- 15581833
TI  - Genotypic analysis of the TGF beta-509 allele in patients with systemic lupus
      erythematosus and Sjogren's syndrome.
AB  - Transforming growth factor beta (TGFbeta) is a secreted protein present in the
      circulation and is a critical regulator of the body's immune system. TGFbeta is
      believed to control several components of the immune system and inhibit
      autoimmune reactions. Systemic lupus erythematosus (SLE) and Sjogren's syndrome
      (SS) are prototypical human autoimmune diseases characterized by the circulating
      autoantibodies directed against nuclear antigens and immune complex deposition in
      various tissues leading to target organ inflammation and damage. Although the
      etiology of SLE is unknown, it has been observed that patients with SLE have
      lower levels of circulating TGFbeta than healthy individuals. In addition, mice
      lacking the TGFbeta1 gene develop a severe autoimmune disease that has features
      of both SS and SLE. Polymorphisms in the TGFbeta1 gene may alter the mRNA
      expression levels and influence the plasma protein concentration. Of the known
      TGFbeta 1 polymorphisms, only the C-509T polymorphism in the promoter region has
      been shown to be significantly associated with the plasma concentrations of
      TGFbeta 1. In this study, we have conducted a blinded study to determine if the 
      509 TGFbeta1 gene polymorphism is associated with SS or SLE. Genomic PCR and RFLP
      analysis of a 441 bp sequence encompassing the -509 polymorphism of the TGFbeta
      gene indicated that there were no statistically significant clinical
      correlations.

PMID- 15581834
TI  - Cryptic translocations involving chromosome 20 in polycythemia vera.
AB  - A systematic cytogenetic study was performed in 49 patients with polycythemia
      vera (PV) in order to investigate the occurrence of subtelomeric rearrangements
      of chromosome 20, the most frequently rearranged chromosome in this
      myeloproliferative disorder. Partial deletion of the long arm of chromosome 20
      was observed in two patients and two cryptic translocations, t(1;20)(p36;q13) and
      t(18;20)(p11;q13) in two others, all previously treated. The localization of the
      breakpoints of the translocated 20 chromosomes was different in the two
      translocations, as shown by fluorescence in situ hybridization (FISH) to
      metaphase chromosomes using BAC clones. Although infrequent (2/49), cryptic
      translocations of chromosome 20 deserve to be detected as preliminary to
      identification of molecular defects in PV.

PMID- 15581835
TI  - Contribution of ultrasonographic examination to the prenatal detection of trisomy
      21: experience from 19 European registers.
AB  - The objective of this study was to evaluate the contribution of ultrasound
      scanning to the prenatal detection of trisomy 21 in a large unselected European
      population. Data from 19 congenital malformation registers in 11 European
      countries were included. The prenatal ultrasound screening programs in the
      countries ranged from no routine screening to three ultrasound investigations per
      patient. Routine serum screening was offered in four of the 11 countries and
      routine screening on the basis of maternal age amniocentesis in all. The results
      show that overall 53% of cases of trisomy 21 were detected prenatally with a
      range from 3% in Lithuania to 88% in Paris. Ninety-eight percent of women whose
      babies were diagnosed before 24 weeks gestation chose to terminate the pregnancy.
      Centres/countries that offer serum screening do not have a significantly higher
      detection rate of trisomy 21 when compared to those that offer maternal age
      amniocentesis and anomaly scanning only. Fifty percent of trisomy 21 cases were
      born to women aged 35 years or more. In conclusions, second trimester ultrasound
      plays an important role in the prenatal diagnosis of trisomy 21. Of those cases
      prenatally diagnosed, 64% of cases in women <35 years and 36% of those in women
      >or=35 years were detected because of an ultrasound finding. Ultrasound soft
      markers accounted for 84% of the scan diagnoses. There is evidence of increasing
      maternal age across Europe with 50% of cases of trisomy 21 born to women aged 35
      years or more.

PMID- 15581836
TI  - Isolated congenital anonychia cases with coincident chromosomal fragility.
AB  - Isolated anonychia without any associated phenotypical disturbances is one of the
      rarest anomalies of congenital nail disorders. Some or all fingers of the hands
      or feet could be affected. Anonychia can be encountered in dermatologic disorders
      like pemphigus, lichen planus, epidermolysis bullosa; it can also be seen as a
      component of some syndromes like Nail-Patella and Cooks syndromes. We present a
      sister couple in whom all fingernails and toenails were lacking without any
      additional physical sign. A fragile chromosomal site was also encountered in
      peripheral chromosome analysis in the long arm of the chromosome 10 in both of
      the cases.

PMID- 15581837
TI  - Non-lethal Hallermann-Streiff syndrome with bone fracture: report of a case.
AB  - The Hallermann-Streiff syndrome is characterized by bird-like face,
      micropthalmia, cataracts, micrognathia, beaked nose, abnormal dentition,
      hypotrichosis, cutaneous atrophy and proportional small stature. We present a 35
      day-old patient with the classical signs except cutaneous atrophy, additionally
      he had a healing fracture at the proximal part of the left radius.

PMID- 15581838
TI  - Partial trisomy 18q11.2-->qter due to de novo unbalanced translocation of
      chromosomes 15 and 18 analyzed by fluorescence in situ hybridization.
AB  - This report presents a case with partial trisomy 18q resulting from de novo
      unbalanced translocation of chromosomes 15 and 18 displaying the features of pure
      trisomy. This is the first reported case with partial trisomy 18q due to
      unbalanced translocation between chromosomes 15 and 18. Clinical findings of our
      case have been compared with the reported cases' had partial trisomy 18q and the
      importance to recognize the cases with chromosome abnormalities to give genetic
      counseling and prenatal diagnosis for subsequent pregnancies has emphasized.

PMID- 15581839
TI  - Partial trisomy 8q and partial monosomy 18p: a case report.
AB  - We report clinical observations and cytogenetic studies of an inherited partial
      trisomy 8q and partial monosomy 18p. A full trisomy 8 syndrome (Warkany syndrome)
      is a clinically recognized syndrome. Partial trisomy 8q has been reported
      sporadically in the literature with variable phenotypes. Partial monosomy 18p,
      deletion of the short arm of chromosome 18, is also a well-recognized syndrome.
      This is the first report to the best of our knowledge of partial trisomy for
      distal 8q and partial monosomy for distal 18p occurring together in a patient.

PMID- 15581840
TI  - A submicroscopic unbalanced subtelomeric translocation t(2p;10q) identified by
      fluorescence in situ hybridization: fetus with increased nuchal translucency and
      normal standard karyotype with later growth and developmental delay,
      rhombencephalosynapsis (RES).
AB  - Reaching an accurate diagnosis in children with mental retardation associated or
      not with dysmorphic signs is important to make precise diagnosis of a syndrome
      and for genetic counseling. A female case with severe growth and development
      delay, dysmorphic features and feeding disorder is presented. Antenataly, the
      fetus was observed to have increased nuchal translucency and a slight hypoplastic
      cerebellum. A standard karyotype was normal. RES and a submicroscopic unbalanced
      subtelomeric translocation t(2p; 10q) were demonstrated after birth. We show that
      within the framework of a collaborative approach, a concerted research of
      submicroscopic subtelomeric rearrangements should be performed in case of mental
      retardation associated with facial dysmorphic features, and when other etiologies
      or non-genetic factors (iatrogenic, toxic, infectious, metabolic...) have been
      ruled out.

PMID- 15581841
TI  - Large duplication 4q25-q34 with mild clinical effect.
AB  - We report on a 5-year-old Tunisian boy with particular dysmorphic features and
      mild mental retardation limited in delayed and poor language acquisition.
      Cytogenetic analysis using RHG banding and FISH using whole chromosome four
      painting probe showed a partial duplication in the long arm of chromosome four.
      Locus specific probes and CGH confirmed the presence of a ''pure'' partial
      trisomy 4q due to de novo direct tandem dup(4)(q25q34). Comparative analysis of
      our case with those published previously, suggests that region 4q31-q33 may be
      involved in the development of the 4q characteristic dysmorphic features and the
      distal band 4q35 may be involved in the development of microcephaly and severe
      mental and growth retardation.

PMID- 15581842
TI  - Trisomy 4 associated with double minute chromosomes and MYC amplification in
      acute myeloblastic leukemia.
AB  - A case of de novo acute myeloblastic leukemia (AML) M2, with trisomy 4 and double
      minute (dmin) chromosomes is reported. Amplification of the MYC gene ascertained
      by FISH was associated with dmin. A review of the literature of trisomy 4-dmin
      associated AML shows that this entity preferentially occurs in elderly women and
      is not always associated with previously identified exposition to mutagens.

PMID- 15581843
TI  - Intranuclear arrangement of human chromosome 12 is reflected in metaphase
      chromosomes as non-random bending.
AB  - We have found a high correlation of non-random bending of human metaphase
      chromosome 12 with the intranuclear arrangement deduced by Nogami et al.
      (Chromosoma 108 (2000) 514), providing further evidence of the relation of non
      random bending and the interphase organization of the nucleus.

PMID- 15581844
TI  - Effect of 5637 conditioned medium (CM) on the mitotic index in the cytogenetic
      evaluation of myeloproliferative disorders.

PMID- 15581845
TI  - Ca2+ binding to sarcoplasmic reticulum ATPase phosphorylated by Pi reveals four
      thapsigargin-sensitive Ca2+ sites in the presence of ADP.
AB  - Sarcoplasmic reticulum (SR) Ca2+-ATPase was phosphorylated by Pi at pH 8.0 in the
      presence of dimethyl sulfoxide (Me2SO). Under these conditions, it was possible
      to measure transient 45Ca2+ binding to the phosphoenzyme. Binding reached 1.2
      Ca2+ per phosphoenzyme (E-PCax) within 10 min in 30% Me2SO, 20 mM MgCl2 and 0.1
      mM Pi and the phosphoenzyme only decreased by 23% during this period. This Ca2+
      binding was abolished by thapsigargin, showing that it is associated with
      functional sites of the Ca2+-ATPase. At 40% Me2SO, simultaneous addition of Ca2+
      and ADP increased Ca2+ binding up to almost four Ca2+ per phosphoenzyme (ADPE
      PCay), revealing a species bearing simultaneously four Ca2+ sites. Both E-PCax
      and ADPE-PCay were further identified as distinct species by (2',3'-O-2(2,4,6
      trinitrophenyl)adenosine 5'-triphosphate) fluorescence, which revealed long-range
      modifications in the Ca2+-transport sites induced by ADP binding to E-P. In
      addition, E-PCax was shown to be a functional intermediate of the cycle leading
      to ATP synthesis provided that Me2SO was diluted. These findings indicate that
      more than two functional Ca2+-sites exist on the functional Ca2+-ATPase unit, and
      that the additional sites become accessible upon ADP addition. This is compatible
      with a four-site model of the SR Ca2+-ATPase allowing simultaneous binding of
      Ca2+ at lumenal and cytosolic sites. The stoichiometries for Ca2+ binding found
      here could either be interpreted as binding of four Ca2+ on a Ca2+-ATPase monomer
      considered as the functional unit or as binding of two Ca2+ per monomer of a
      functional dimer.

PMID- 15581846
TI  - Effects of angiotensin II on NaPi-IIa co-transporter expression and activity in
      rat renal cortex.
AB  - The kidney plays a major role in reabsorption of phosphate with the majority
      occurring in the proximal tubule (PT). The type IIa sodium-phosphate co
      transporter (NaPi-IIa) is the main player in PT. The purpose of current study was
      to determine the effect of angiotensin II (A-II) on membrane expression of NaPi
      IIa in the rat renal cortex. A-II (500 ng/kg/min) was chronically infused into
      the Sprague-Dawley rats by miniosmotic pump for 7 days. The arterial pressure and
      circulating plasma A-II level along with urine output were markedly increased in
      A-II rats. There was diuresis but no natriuresis. The phosphate excretion
      increased sevenfold on day 4 and 5.7-fold on day 7. There was no change in Na
      dependent Pi uptake in brush-border membrane (BBM) vesicles between A-II-treated
      group and control on day 4, however, there was a 43% increase on day 7. Western
      blot analysis of NaPi-IIa protein abundance showed a parallel pattern: no change
      after 4 days of treatment and a 48% increase after 7 days of treatment. However,
      Northern blot analysis of cortical RNA showed no change in NaPi-IIa mRNA
      abundance on day 7. A-II stimulation of Na/Pi co-transport activity is a result
      of increases in the expression of BBM NaPi-IIa protein level and that stimulation
      is most likely mediated by posttranscriptional mechanisms.

PMID- 15581847
TI  - Reconstitution into liposomes of the glutamine/amino acid transporter from renal
      cell plasma membrane: functional characterization, kinetics and activation by
      nucleotides.
AB  - The glutamine/amino acid transporter was solubilized from rat renal apical plasma
      membrane (brush-border membrane) with C12E8 and reconstituted into liposomes by
      removing the detergent from mixed micelles by hydrophobic chromatography on
      Amberlite XAD-4. The reconstitution was optimised with respect to the protein
      concentration, the detergent/phospholipid ratio and the number of passages
      through a single Amberlite column. The reconstituted glutamine/amino acid
      transporter catalysed a first-order antiport reaction stimulated by external, not
      internal, Na+. Optimal activity was found at pH 7.0. The sulfhydryl reagents
      HgCl2, mersalyl and p-hydroxymercuribenzoate and the amino acids alanine, serine,
      threonine, cysteine, asparagine, methionine and valine strongly inhibited the
      transport, whereas the amino acid analogue methylaminoisobutyrate had no effect.
      Glutamine, alanine, serine, asparagine, threonine were efficiently translocated
      from outside to inside and from inside to outside the proteoliposomes as well.
      Cysteine and valine were translocated preferentially from outside to inside. The
      Km for glutamine on the external and internal side of the transporter was 0.47
      and 11 mM, respectively; the values were not influenced by the type of the
      counter substrate. The transporter is functionally asymmetrical and it is
      unidirectionally inserted into the proteoliposomal membrane with an orientation
      corresponding to that of the native membrane. By a bisubstrate kinetic analysis
      of the glutamine antiport, a random simultaneous mechanism was found. The
      glutamine antiport was strongly stimulated by internal nucleoside triphosphates
      and, to a lower extent, by pyrophoshate. The reconstituted glutamine/amino acid
      transporter functionally corresponds to the ASCT2 protein.

PMID- 15581848
TI  - Differential effect of imipramine and related compounds on Mg2+ efflux from rat
      erythrocytes.
AB  - The effect of imipramine on Mg2+ efflux in NaCl medium (Na+/Mg2+ antiport), on
      Mg2+ efflux in choline.Cl medium (choline/Mg2+ antiport) and on Mg2+ efflux in
      sucrose medium (Cl- -coupled Mg2+ efflux) was investigated in rat erythrocytes.
      In non-Mg2+-loaded rat erythrocytes, imipramine stimulated Na+/Mg2+ antiport but
      inhibited choline/Mg2+ antiport and Cl- -coupled Mg2+ efflux. The same effect
      could be obtained by several other compounds structurally related to imipramine.
      These drugs contain a cyclic hydrophobic ring structure to which a four-membered
      secondary or tertiary amine side chain is attached. At a physiological pH, the
      amine side chain expresses a cationic choline-like structure. The inhibitory
      effect on choline/Mg2+ antiport is lost when the amine side chain is modified or
      abandoned, pointing to competition of the choline-like side chain with choline or
      another cation at the unspecific choline antiporter or at the Cl- -coupled Mg2+
      efflux. Other related drugs either stimulated Na+/Mg2+ antiport and choline/Mg2+
      antiport, or they were ineffective. For stimulation of Na+/Mg2+ antiport and
      choline/Mg2+ antiport, there is no specific common structural motif of the drugs
      tested. The effects of imipramine on Na+/Mg2+ antiport and choline/Mg2+ antiport
      are not mediated by PKCalpha but are caused by a direct reaction of imipramine
      with these transporters. By increasing the intracellular Mg2+ concentration, the
      stimulation of Na+/Mg2+ antiport at a physiological intracellular Mg2+
      concentration changed to an inhibition of Na+/Mg2+ antiport. This effect can be
      explained by the hypothesis that Mg2+ loading induced an allosteric transition of
      the Mg2+/Mg2+ exchanger with low Na+/Mg2+ antiport capacity to the Na+/Mg2+
      antiporter with high Na+/Mg2+ antiport capacity. Both forms of the Mg2+ exchanger
      may be differently affected by imipramine.

PMID- 15581849
TI  - On the mechanism of non-endosomial peptide-mediated cellular delivery of nucleic
      acids.
AB  - Recently, we described a new strategy for the delivery of nucleic acids into
      mammalian cells, based on an amphipathic peptide of 27 residues called MPG, which
      was designed on the basis of a hydrophobic domain derived from a fusion sequence
      associated with a nuclear localization sequence and separated by a linker. This
      peptide carrier constitutes a powerful tool for the delivery of nucleic acids in
      cultured cells, without requiring any covalent coupling. We have examined the
      conformational states of MPG in its free form and complexed with a cargo, as well
      as its ability to interact with phospholipids, and have investigated the
      structural consequences of these interactions. In spite of its similarity to the
      similarly designed cell-penetrating peptide Pep-1, MPG behaves significantly
      differently from the conformational point of view. Circular dichroism (CD)
      analysis reveals a transition from a nonstructured to a beta-sheet conformation
      upon interaction with phospholipids. We propose that the membrane crossing
      process involves formation of a transient transmembrane pore-like structure.
      Partial conformational change of MPG is associated with formation of a complex
      with its cargo, and an increase in sheet content occurs upon association with the
      cell membrane.

PMID- 15581850
TI  - Antibacterial activity and pore-forming properties of ceratotoxins: a mechanism
      of action based on the barrel stave model.
AB  - Ceratotoxins are alpha-helical cationic peptides isolated from the medfly
      Ceratitis capitata. These amphipathic peptides were found to display strong
      antibacterial activity and weak hemolytic activity. When reconstituted into
      planar lipid bilayers, ceratotoxins developed highly asymmetric I/V curves under
      voltage ramps and formed, in single-channel experiments, well-defined voltage
      dependent ion channels according to the barrel stave model. The antibacterial
      activity and pore-forming properties of these molecules were well correlated.
      Similar experiments performed with synthesized truncated fragments showed that
      the C-terminal domain of ceratotoxins is strongly implicated in the formation of
      helical bundles in the membrane whereas the largely cationic N-terminal region is
      likely to anchor ceratotoxins on the lipid surface.

PMID- 15581851
TI  - The synthesis of SNAT2 transporters is required for the hypertonic stimulation of
      system A transport activity.
AB  - In cultured human fibroblasts incubated under hypertonic conditions, the
      stimulation of system A for neutral amino acid transport, associated to the
      increased expression of the mRNA for SNAT2 transporter, leads to an expanded
      intracellular amino acid pool and to the recovery of cell volume. A protein of
      nearly 60 kDa, recognized by an antiserum against SNAT2, is increased both in the
      pool of biotinylated membrane proteins and in the total cell lysate of
      hypertonically stressed cells. The increased level of SNAT2 transporters in
      hypertonically stressed cells is confirmed by immunocytochemistry. DRB, an
      inhibitor of transcription, substantially inhibits the increase of SNAT2 proteins
      on the plasma membrane, completely suppresses the stimulation of system A
      transport activity, and markedly delays the cell volume recovery observed during
      the hypertonic treatment. On the contrary, if the transport activity of system A
      is adaptively increased by amino acid starvation in the presence of DRB, the
      increase of SNAT2 transporters on the plasma membrane is still clearly detectable
      and the transport change only partially inhibited. It is concluded that the
      synthesis of new SNAT2 transporters is essential for the hypertonic stimulation
      of transport system A, but accounts only in part for the adaptive increase of the
      system.

PMID- 15581852
TI  - PcMtr, an aromatic and neutral aliphatic amino acid permease of Penicillium
      chrysogenum.
AB  - The gene encoding an aromatic and neutral aliphatic amino acid permease of
      Penicillium chrysogenum was cloned, functionally expressed and characterized in
      Saccharomyces cerevisiae M4276. The permease, designated PcMtr, is structurally
      and functionally homologous to Mtr of Neurospora crassa, and unrelated to the
      Amino Acid Permease (AAP) family which includes most amino acid permeases in
      fungi. Database searches of completed fungal genome sequences reveal that Mtr
      type permeases are not widely distributed among fungi, suggesting a specialized
      function.

PMID- 15581853
TI  - Transport of ions across peritoneal membrane.
AB  - The electrical conductance of ions across the peritoneal membrane of young
      buffalo (approximately 18-24 months old) has been recorded. Aqueous solutions of
      NaF, NaNO3, NaCl, Na2SO4, KF, KNO3, KCl, K2SO4, MgCl2, CaCl2, CrCl3, MnCl2,
      FeCl3, CoCl2, and CuCl2 were used. The conductance values have been found to
      increase with increase in concentration as well as with temperature (15 to 35
      degrees C) in these cases. The slope of plots of specific conductance, kappa,
      versus concentration exhibits a decrease in its values at relatively higher
      concentrations compared to those in extremely dilute solutions. Also, such slopes
      keep on increasing with increase in temperature. In addition, the conductance
      also attains a maximum limiting value at higher concentrations in the said cases.
      This may be attributed to a progressive accumulation of ionic species within the
      membrane. The kappa values of electrolytes follow the sequence for the anions:
      SO4(2-)>Cl->NO3->F- while that for the cations:
      K+>Na+>Ca2+>Mn2+>Co2+>Cu2+>Mg2+>Cr3+>Fe3+. In addition, the diffusion of ions
      depends upon the charge on the membrane and its porosity. The membrane porosity
      in relation to the size of the hydrated species diffusing through the membrane
      appears to determine the above sequence. As the diffusional paths in the membrane
      become more difficult in aqueous solutions, the mobility of large hydrated ions
      gets impeded by the membrane framework and the interaction with the fixed charge
      groups on the membrane matrix. Consequently, the membrane pores reduce the
      conductance of small ions, which are much hydrated. An increase in conductance
      with increase in temperature may be due to the state of hydration, which implies
      that the energy of activation for the ionic transport across the membrane follows
      the sequence of crystallographic radii of ions accordingly. The Eyring's
      equation, kappa=(RT/Nh)exp[-DeltaH*/RT]exp[DeltaS*/R], has been found suitable
      for explaining the temperature dependence of conductance in the said cases. This
      is apparent from the linear plots of log[kappaNh/RT] versus 1/T. The results
      indicate that the permeation of ions through the membrane giving negative values
      of DeltaS* suggest that there may be formation of either covalent linkage between
      the penetrating ions and the membrane material or else the permeation may not be
      the rate-determining step. On the one hand, a high DeltaS* value associated with
      the high value of energy of activation, Ea, for diffusion may suggest the
      existence of either a large zone of activation or loosening of more chain
      segments of the membrane. On the other hand, low value of DeltaS* implies that
      converse is true in such cases, i.e., either a small zone of activation or no
      loosening of the membrane structure upon permeation.

PMID- 15581854
TI  - Miscibility of acyl-chain defined phosphatidylcholines with N-palmitoyl
      sphingomyelin in bilayer membranes.
AB  - In this study we have used differential scanning calorimetry (DSC) to study the
      miscibility of different saturated phosphatidylcholines (PCs) with D-erythro-N
      palmitoyl-sphingomyelin (16:0-SM). Information about the miscibility was obtained
      by observing the thermotropic phase behavior of binary mixtures of saturated PCs
      and 16:0-SM. The results obtained showed that PC miscibility in 16:0-SM was
      markedly affected by the PC acyl-chain composition. According to phase diagrams
      prepared from DSC data and the mid-transition temperatures of the main phase
      transition, the PC which formed the most ideal mixture with 16:0-SM was di-14:0
      PC. However, the cooperativity of the main transition in PC/16:0-SM bilayers
      increased until the average acyl-chain length in the PC reached 15 carbons. Based
      on the criteria of the most ideal miscibility or the highest cooperativity of the
      main transition, we conclude that di-14:0-PC, 15:0/15:0-PC, and 14:0/16:0-PC
      interacted most favorably with 16:0-SM in bilayer membranes. Di-16:0-PC, to which
      16:0-SM is often compared in biophysical studies, showed much less ideal
      miscibility.

PMID- 15581855
TI  - Description and role in proliferation of iberiotoxin-sensitive currents in
      different human mammary epithelial normal and cancerous cells.
AB  - Several studies suggested that potassium channels are involved in the
      proliferation of cancer cells but the involvement of the large conductance Ca2+
      activated K+ channels (BKCa) in the cancerous phenomenon is still controversial.
      In the present study, we used iberiotoxin, a specific blocker of BKCa, and report
      the activity of an iberiotoxin-sensitive current in various human breast cancer
      cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and MDA-MB-435s) as well as in normal
      mammary epithelial cells (HME). Iberiotoxin and NS1619, an activator of BKCa, did
      not interfere with either cell proliferation or with the invasive properties of
      the cells, under normal culture conditions. However, extracellular pulses of ATP,
      which induced transient increases in intracellular Ca2+ concentration, revealed a
      significant reduction effect of iberiotoxin on cell proliferation. We conclude
      that the iberiotoxin-sensitive current is not involved in cell proliferation in
      basal conditions but participates when the intracellular Ca2+ concentration is
      increased. These experiments also suggest that BKCa channels are not involved in
      the cancerous transformation and are probably a relic from normal cells.

PMID- 15581856
TI  - Interactions of lipid monolayers with the natural biopolymer hyaluronic acid.
AB  - The interaction of the natural mucopolysaccharide hyaluronic acid with different
      lipids, present in the natural membranes, was studied at the lipid/water
      interface using thermodynamic methods and X-ray diffraction. The results show
      that this biopolymer modifies the properties and the structure of the lipid
      monolayer. The two-dimensional crystalline lattice and domain structure of the
      charged octadecylamine monolayer are strongly disturbed by the hyaluronic acid,
      the monolayer compressibility increases and the monolayer collapse pressure drops
      down. In addition, the presence of charged lipid interfaces influences the
      structural organisation of the hyaluronic acid at the membrane/water interfaces.
      The impacts of these results on the structural organisation at the membrane
      interface are discussed.

PMID- 15581857
TI  - The role of beta2-glycoprotein I in liposome-hepatocyte interaction.
AB  - Adsorption of serum proteins to the liposomal surface plays a critical role in
      liposome clearance from the blood. The aim of this study was to investigate the
      role of liposome-adsorbed serum proteins in the interaction of liposomes with
      hepatocytes. We analyzed the serum proteins adsorbing to the surface of
      differently composed small unilamellar liposomes during incubation with human or
      rat serum, and found that one protein, with a molecular weight of around 55 kDa,
      adsorbed in a large amount to negatively charged liposomes containing
      phosphatidylserine (PS) or phosphatidylglycerol (PG). The binding was dependent
      on the liposomal charge density. The approximately 55-kDa protein was identified
      as beta2-glycoprotein I (beta2GPI) by Western blotting. Despite the high affinity
      of beta2GPI for strongly negatively charged liposomes, in vitro uptake and
      binding experiments with isolated rat hepatocytes, Kupffer cells or liver
      endothelial cells, and with HepG2 cells showed no enhancing effect of this
      protein on the association of negatively charged liposomes with any of these
      cells. On the contrary, an inhibitory effect was observed. We conclude that
      despite abundant adsorption to negatively charged liposomes, beta2GP1 inhibits,
      rather than enhances, liposome uptake by liver cells.

PMID- 15581858
TI  - The effect of merulinic acid on biomembranes.
AB  - Merulinic acid (heptadecenylresorcinolic acid, resorcinolic acid) is one of the
      members of resorcinolic lipids, the natural amphiphilic long-chain homologues of
      orcinol (1,3-dihydroksy-5-methylbenzene). In the present study, membrane
      properties of merulinic acid were investigated. Merulinic acid exhibits strong
      haemolytic activity against sheep erythrocytes (EH50 of 5+/-2 microM) regardless
      of the form of its application-direct injection into the erythrocyte suspension
      or injection as merulinic acid-enriched liposomes. The lysis of erythrocytes
      induced by merulinic acid was inhibited by the presence of divalent cations. The
      effectivity of the protection of erythrocytes was highest for Zn2+ and weakest
      for Mn2+. Merulinic acid at low concentrations also exhibits the ability for
      protection of cells against their lysis in hypoosmotic solutions. This protective
      effect is significant as, at 10 microM concentration of merulinic acid, the
      extent of osmotically induced cell lysis is reduced by approximately 40%.
      Merulinic acid induces increased permeability of liposomal vesicles. This effect
      was shown to be dependent on the composition of liposomal bilayer and it was
      stronger when lipid bilayer contained glycolipids (MGDG and DGDG) and
      sphingomyelin. Changes of TMA-DPH and NBD-PE fluorescence polarization show that
      the degree of merulinic acid incorporation into liposomal membrane is not very
      high. The polar "heads" of the molecules of investigated compounds are localized
      on the level of fatty acid's ester bonds in phospholipid molecules. Merulinic
      acid caused the increased fluorescence of the membrane potential fragile probe.
      This indicated an alteration of the surface charge and a decrease of the local pH
      at the membrane surface. This effect was visible in both low- and high-ionic
      strength environment. Merulinic acid causes also a decrease in activity of the
      membrane-bound enzyme acetylcholinesterase.

PMID- 15581859
TI  - Uptake of cell-penetrating peptides is dependent on peptide-to-cell ratio rather
      than on peptide concentration.
AB  - The influence of the peptide-to-cell ratio and energy depletion on uptake and
      degradation of the cell-penetrating peptides (CPPs) MAP (model amphipathic
      peptide) was investigated. The intracellular concentration of the CPPs, MAP and
      penetratin was monitored while varying the number of cells at fixed peptide
      concentration and incubation volume, or changing the concentration and incubation
      volume at fixed cell number. The uptake of CPPs was shown to be dependent on the
      peptide/cell ratio. At given peptide concentration and incubation volume, the
      intracellular concentration of peptide increased with lower cell number. At given
      cell number, doubling of the incubation volume increased intracellular peptide
      concentration to a similar extent as the doubling in incubation concentration.
      From a practical view, this means that the peptide/cell ratio has at least the
      same importance for the uptake of CPPs as the used peptide concentration. No
      influence of the peptide/cell ratio was found for the cellular uptake of peptide
      nucleic acid (PNA), or a non-amphipathic MAP analogue, investigated in parallel
      for comparison purposes. Energy depletion resulted in significantly reduced
      quantities of intracellular fluorescence label. Moreover, we show that this
      difference is mainly due to a membrane-impermeable fluorescent-labelled
      degradation product, which is lacking in energy-depleted cells. The mechanism of
      its generation is not likely to be endosomal degradation of endocytosed material,
      as it is not chloroquine- or brefeldin-sensitive.

PMID- 15581860
TI  - Activity regulation of the betaine transporter BetP of Corynebacterium glutamicum
      in response to osmotic compensation.
AB  - As a response to hyperosmotic stress bacterial cells accumulate compatible
      solutes by synthesis or by uptake. Beside the instant activation of uptake
      systems after an osmotic upshift, transport systems show also a second, equally
      important type of regulation. In order to adapt the pool size of compatible
      solutes in the cytoplasm to the actual extent of osmotic stress, cells down
      regulate solute uptake when the initial osmotic stress is compensated. Here we
      describe the role of the betaine transporter BetP, the major uptake carrier for
      compatible solutes in Corynebacterium glutamicum, in this adaptation process. For
      this purpose, betP was expressed in cells (C. glutamicum and Escherichia coli),
      which lack all known uptake systems for compatible solutes. Betaine uptake
      mediated by BetP as well as by a truncated form of BetP, which is deregulated in
      its response to hyperosmotic stress, was dissected into the individual substrate
      fluxes of unidirectional uptake, unidirectional efflux and net uptake. We
      determined a strong decrease of unidirectional betaine uptake by BetP in the
      adaptation phase. The observed decrease in net uptake was thus mainly due to a
      decrease of Vmax of BetP and not a consequence of the presence of separate efflux
      system(s). These results indicate that adaptation of BetP to osmotic compensation
      is different from activation by osmotic stress and also different from previously
      described adaptation mechanisms in other organisms. Cytoplasmic K+, which was
      shown to be responsible for activation of BetP upon osmotic stress, as well as a
      number of other factors was ruled out as triggers for the adaptation process. Our
      results thus indicate the presence of a second type of signal input in the
      adaptive regulation of osmoregulated carrier proteins.

PMID- 15581861
TI  - Membrane cholesterol content modulates activation of BK channels in colonic
      epithelia.
AB  - Changes in the level of membrane cholesterol regulate a variety of signaling
      processes including those mediated by acylated signaling molecules that localize
      to lipid rafts. Recently several types of ion channels have been shown to have
      cholesterol-dependent activity and to localize to lipid rafts. In this study, we
      have investigated the role of cholesterol in the regulation of ion transport in
      colonic epithelial cells. We observed that methyl-beta-cyclodextrin (MbetaCD), a
      cholesterol-sequestering molecule, activated transepithelial short circuit
      current (Isc), but only from the basolateral side. Similar results were obtained
      with a cholesterol-binding agent, filipin, and with the sphingomyelin-degrading
      enzyme, sphingomyelinase. Experiments with DeltaF508CFTR mutant mice indicated
      that raft disruption affected CFTR-mediated anion secretion, while
      pharmacological studies showed that this effect was due to activation of
      basolateral large conductance Ca2+-activated K+ (BK) channels. Sucrose density
      gradient centrifugation studies demonstrated that BK channels were normally
      present in the high-density fraction containing the detergent-insoluble
      cytoskeleton, and that following treatment with MbetaCD, BK channels
      redistributed into detergent-soluble fractions. Our evidence therefore implicates
      novel high-density cholesterol-enriched plasma membrane microdomains in the
      modulation of BK channel activation and anion secretion in colonic epithelia.

PMID- 15581862
TI  - Embryogenesis and blastocyst development after somatic cell nuclear transfer in
      nonhuman primates: overcoming defects caused by meiotic spindle extraction.
AB  - Therapeutic cloning or nuclear transfer for stem cells (NTSC) seeks to overcome
      immune rejection through the development of embryonic stem cells (ES cells)
      derived from cloned blastocysts. The successful derivation of a human embryonic
      stem cell (hESC) line from blastocysts generated by somatic cell nuclear transfer
      (SCNT) provides proof-of-principle for "therapeutic cloning," though immune
      matching of the differentiated NT-hES remains to be established. Here, in
      nonhuman primates (NHPs; rhesus and cynomologus macaques), the strategies used
      with human SCNT improve NHP-SCNT development significantly. Protocol improvements
      include the following: enucleation just prior to metaphase-II arrest; extrusion
      rather than extraction of the meiotic spindle-chromosome complex (SCC); nuclear
      transfer by electrofusion with simultaneous cytoplast activation; and sequential
      media. Embryo transfers (ET) of 135 SCNT-NHP into 25 staged surrogates did not
      result in convincing evidence of pregnancies after 30 days post-ET. These results
      demonstrate that (i) protocols optimized in humans generate preimplantation
      embryos in nonhuman primates; (ii) some, though perhaps not yet all, hurdles in
      deriving NT-nhpES cells from cloned macaque embryos (therapeutic cloning) have
      been overcome; (iii) reproductive cloning with SCNT-NHP embryos appears
      significantly less efficient than with fertilized embryos; (iv) therapeutic
      cloning with matured metaphase-II oocytes, aged oocytes, or "fertilization
      failures" might remain difficult since enucleation is optimally performed prior
      to metaphase-II arrest; and (v) challenges remain for producing reproductive
      successes since NT embryos appear inferior to fertilized ones due to spindle
      defects resulting from centrosome and motor deficiencies that produce aneuploid
      preimplantation embryos, among other anomalies including genomic imprinting,
      mitochondrial and cytoplasmic heterogeneities, cell cycle asynchronies, and
      improper nuclear reprogramming.

PMID- 15581863
TI  - WAVE1 intranuclear trafficking is essential for genomic and cytoskeletal dynamics
      during fertilization: cell-cycle-dependent shuttling between M-phase and
      interphase nuclei.
AB  - A-kinase-anchoring proteins (AKAP) help regulate the intracellular organization
      of cyclic AMP-dependent kinase (PKA) and actin within somatic cells. Elevated
      levels of cAMP also help maintain meiotic arrest in immature oocytes, with AKAPs
      implicated as critical mediators but poorly understood during this process. Here
      we test the hypothesis that the AKAP WAVE1 is required during mammalian
      fertilization, and identify a nuclear localization of WAVE1 that is independent
      of actin and actin-related proteins (Arp). Immunofluorescence and
      immunoprecipitation experiments show a redistribution of WAVE1 from the cortex in
      germinal vesicle (GV) oocytes to cytoplasmic foci in oocytes arrested in second
      meiosis (Met II). Following sperm entry, WAVE1 relocalizes to the developing male
      and female pronuclei. Association of WAVE1 with a regulatory subunit of PKA is
      detected in both Met II oocytes and pronucleate zygotes, but interaction with Arp
      2/3 is observed only in Met II oocytes. WAVE1 redistributes to the cytoplasm upon
      nuclear envelope breakdown at mitosis, and concentrates at the cleavage furrow
      during embryonic cell division. Blocking nuclear pore formation with
      microinjected wheat germ agglutinin does not inhibit the nuclear localization of
      WAVE1, suggesting that this event precedes nuclear envelope formation. Neither
      depolymerization nor stabilization of actin affects WAVE1 distribution.
      Microtubule stabilization with Taxol, however, redistributes WAVE1 to the
      centrosome, and anti-WAVE1 antibodies prevent both the nuclear distribution of
      WAVE1 and the migration and apposition of pronuclei. These findings show that
      WAVE1 sequestration to the nucleus is required during fertilization, and is an
      actin-independent event that relies on dynamic microtubules but not nuclear
      pores.

PMID- 15581864
TI  - Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development.
AB  - In the developing limb, Bmp4 is expressed in the apical ectodermal ridge (AER)
      and underlying mesoderm. Insight into the function of Bmp4 in limb development
      has been hampered by the early embryonic lethality of Bmp4 null embryos. We
      directly investigated Bmp4 using a conditional null allele of Bmp4 and the
      Prx1(cre) transgene to inactivate Bmp4 in limb bud mesoderm. The limb bud
      mesoderm of Prx1(cre);Bmp4 mutants was defective in production of Bmp4 but still
      competent to respond to Bmp signaling. Prx1(cre);Bmp4 mutant embryos had
      defective digit patterning including hindlimb preaxial polydactyly with posterior
      digit transformations. The Prx1(cre);Bmp4 mutants also had postaxial polydactyly
      with digit five duplications. Bmp4 mutant limbs had delayed induction and
      maturation of the AER that resulted in expanded Shh signaling. Moreover, the AER
      persisted longer in the Bmp4 mutant limb buds exposing the forming digits to
      prolonged Fgf8 signaling. Our data show that Bmp4 in limb mesoderm regulates AER
      induction and maturation and implicate signaling from the AER in regulation of
      digit number and identity.

PMID- 15581865
TI  - Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste
      papilla development.
AB  - Taste papillae are ectodermal specializations that serve to house and distribute
      the taste buds and their renewing cell populations in specific locations on the
      tongue. We previously showed that Sonic hedgehog (Shh) has a major role in
      regulating the number and spatial pattern of fungiform taste papillae on
      embryonic rat tongue, during a specific period of papilla formation from the
      prepapilla placode. Now we have immunolocalized the Shh protein and the Patched
      receptor protein (Ptc), and have tested potential roles for Shh in formation of
      the tongue, emergence of papilla placodes, development of papilla number and
      size, and maintenance of papillae after morphogenesis is advanced. Cultures of
      entire embryonic mandible or tongues from gestational days 12 to 18 [gestational
      or embryonic days (E)12-E18] were used, in which tongues and papillae develop
      with native spatial, temporal, and molecular characteristics. The Shh signaling
      pathway was disrupted with addition of cyclopamine, jervine, or the 5E1 blocking
      antibody. Shh and Ptc proteins are diffuse in prelingual tissue and early tongue
      swellings, and are progressively restricted to papilla placodes and then to
      regions of developing papillae. Ptc encircles the dense Shh immunoproduct in
      papillae at various stages. When the Shh signal is disrupted in cultures of E12
      mandible, tongue formation is completely prevented. At later stages of tongue
      culture initiation, Shh signal disruption alters development of tongue shape
      (E13) and results in a repatterned fungiform papilla distribution that does not
      respect normally papilla-free tongue regions (E13-E14). Only a few hours of Shh
      signal disruption can irreversibly alter number and location of fungiform
      papillae on anterior tongue and elicit papilla formation on the intermolar
      eminence. However, once papillae are well formed (E16-E18), Shh apparently does
      not have a clear role in papilla maintenance, nor does the tongue retain
      competency to add fungiform papillae in atypical locations. Our data not only
      provide evidence for inductive and morphogenetic roles for Shh in tongue and
      fungiform papilla formation, but also suggest that Shh functions to maintain the
      interpapilla space and papilla-free lingual regions. We propose a model for Shh
      function at high concentration to form and maintain papillae and, at low
      concentration, to activate between-papilla genes that maintain a papilla-free
      epithelium.

PMID- 15581866
TI  - Abnormalities of caudal pharyngeal pouch development in Pbx1 knockout mice mimic
      loss of Hox3 paralogs.
AB  - Pbx1 is a TALE-class homeodomain protein that functions in part as a cofactor for
      Hox class homeodomain proteins. Previous analysis of the in vivo functions of
      Pbx1 by targeted mutagenesis in mice has revealed roles for this gene in skeletal
      patterning and development and in the organogenesis of multiple systems. Both RNA
      expression and protein localization studies have suggested a possible role for
      Pbx1 in pharyngeal region development. As several Hox mutants have distinct
      phenotypes in this region, we investigated the potential requirement for Pbx1 in
      the development of the pharyngeal arches and pouches and their organ derivatives.
      Pbx1 homozygous mutants exhibited delayed or absent formation of the caudal
      pharyngeal pouches, and disorganized patterning of the third pharyngeal pouch.
      Formation of the third pouch-derived thymus/parathyroid primordia was also
      affected, with absent or hypoplastic primordia, delayed expression of organ
      specific differentiation markers, and reduced proliferation of thymic epithelium.
      The fourth pouch and the fourth pouch-derived ultimobranchial bodies were usually
      absent. These phenotypes are similar to those previously reported in Hoxa3(-/-)
      single mutants and Hoxa1(-/-);Hoxb1(-/-) or Hoxa3(+/-);Hoxb3(-/-);Hoxd3(-/-)
      compound mutants, suggesting that Pbx1 acts together with multiple Hox proteins
      in the development of the caudal pharyngeal region. However, some aspects of the
      Pbx1 mutant phenotype included specific defects that were less severe than those
      found in known Hox mutant mice, suggesting that some functions of Hox proteins in
      this region are Pbx1-independent.

PMID- 15581867
TI  - Control of retinoic acid synthesis and FGF expression in the nasal pit is
      required to pattern the craniofacial skeleton.
AB  - Endogenous retinoids are important for patterning many aspects of the embryo
      including the branchial arches and frontonasal region of the embryonic face. The
      nasal placodes express retinaldehyde dehydrogenase-3 (RALDH3) and thus retinoids
      from the placode are a potential patterning influence on the developing face. We
      have carried out experiments that have used Citral, a RALDH antagonist, to
      address the function of retinoid signaling from the nasal pit in a whole embryo
      model. When Citral-soaked beads were implanted into the nasal pit of stage 20
      chicken embryos, the result was a specific loss of derivatives from the lateral
      nasal prominences. Providing exogenous retinoic acid residue development of the
      beak demonstrating that most Citral-induced defects were produced by the specific
      blocking of RA synthesis. The mechanism of Citral effects was a specific increase
      in programmed cell death on the lateral (lateral nasal prominence) but not the
      medial side (frontonasal mass) of the nasal pit. Gene expression studies were
      focused on the Bone Morphogenetic Protein (BMP) pathway, which has a well
      established role in programmed cell death. Unexpectedly, blocking RA synthesis
      decreased rather than increased Msx1, Msx2, and Bmp4 expression. We also examined
      cell survival genes, the most relevant of which was Fgf8, which is expressed
      around the nasal pit and in the frontonasal mass. We found that Fgf8 was not
      initially expressed along the lateral side of the nasal pit at the start of our
      experiments, whereas it was expressed on the medial side. Citral prevented
      upregulation of Fgf8 along the lateral edge and this may have contributed to the
      specific increase in programmed cell death in the lateral nasal prominence.
      Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue
      most of the morphological defects and was able to prevent a decrease in retinoic
      acid receptorbeta (Rarbeta) expression caused by Citral. Together, our results
      demonstrate that endogenous retinoids act upstream of FGF8 and the balance of
      these two factors is critical for regulating programmed cell death and
      morphogenesis in the face. In addition, our data suggest a novel role for
      endogenous retinoids from the nasal pit in controlling the precise downregulation
      of FGF in the center of the frontonasal mass observed during normal vertebrate
      development.

PMID- 15581868
TI  - PDK1 is required for the hormonal signaling pathway leading to meiotic resumption
      in starfish oocytes.
AB  - Meiotic resumption is generally under the control of an extracellular maturation
      inducing hormone. It is equivalent to the G2-M phase transition in somatic cell
      mitosis and is regulated by cyclin B-Cdc2 kinase. However, the complete signaling
      pathway from the hormone to cyclin B-Cdc2 is yet unclear in any organism. A model
      system to analyze meiotic resumption is the starfish oocyte, in which Akt/protein
      kinase B (PKB) plays a key mediator in hormonal signaling that leads to cyclin B
      Cdc2 activation. Here we show in starfish oocytes that when PDK1 activity is
      inhibited by a neutralizing antibody, maturation-inducing hormone fails to induce
      cyclin B-Cdc2 activation at the meiotic G2-M phase transition, even though PDK2
      activity becomes detectable. These observations assign a novel role to PDK1 for a
      hormonal signaling intermediate toward meiotic resumption. They further support
      that PDK2 is a molecule distinct from PDK1 and Akt, and that PDK2 activity is not
      sufficient for the full activation of Akt in the absence of PDK1 activity.

PMID- 15581869
TI  - Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse
      development.
AB  - Histone methylation acts as an epigenetic regulator of chromatin activity through
      the modification of arginine and lysine residues on histones H3 and H4. In the
      case of lysine, this includes the formation of mono-, di-, or trimethyl groups,
      each of which is presumed to represent a distinct functional state at the
      cellular level. To examine the potential developmental roles of these
      modifications, we determined the global patterns of lysine methylation involving
      K9 on histone H3 and K20 on histone H4 in midgestation mouse embryos. For each
      lysine target site, we observed distinct subnuclear distributions of the mono-
      and trimethyl versions in 10T1/2 cells that were conserved within primary
      cultures and within the 3D-tissue architecture of the embryo. Interestingly,
      three of these modifications, histone H3 trimethyl K9, histone H4 monomethyl K20,
      and histone H4 trimethyl K20 exhibited marked differences in their distribution
      within the neuroepithelium. Specifically, both histone H3 trimethyl K9 and H4
      monomethyl K20 were elevated in proliferating cells of the neural tube, which in
      the case of the K9 modification was limited to mitotic cells on the luminal
      surface. In contrast, histone H4 trimethyl K20 was progressively lost from these
      medial regions and became enriched in differentiating neurons in the
      ventrolateral neural tube. The inverse relationship of histone H4 K20 methyl
      derivatives is even more striking during skeletal and cardiac myogenesis where
      the accumulation of the trimethyl modification in pericentromeric heterochromatin
      suggests a role in gene silencing in postmitotic muscle cells. Importantly, our
      results establish that histone lysine methylation occurs in a highly dynamic
      manner that is consistent with their function in an epigenetic program for cell
      division and differentiation.

PMID- 15581870
TI  - C. elegans peb-1 mutants exhibit pleiotropic defects in molting, feeding, and
      morphology.
AB  - Caenorhabditis elegans PEB-1 is a novel DNA-binding protein expressed in most
      pharyngeal cell types and outside the pharynx in the hypodermis, hindgut, and
      vulva. Previous RNAi analyses indicated that PEB-1 is required for normal
      morphology of these tissues and growth; however, the peb-1 null phenotype was
      unknown. Here we describe the deletion mutant peb-1(cu9) that not only exhibits
      the morphological defects observed in peb-1(RNAi) animals, but also results in
      penetrant larval lethality characterized by defects in pharyngeal function and
      molting. Consistent with a function in molting, we found that PEB-1 was
      detectable in all hypodermal and hindgut cells underlying the cuticle. Comparison
      to molting-defective lrp-1(ku156) mutants revealed that the peb-1(cu9) mutants
      were particularly defective in shedding the pharyngeal cuticle, and this defect
      likely contributed to feeding defects and lethality. Most markers of pharyngeal
      cell differentiation examined were expressed normally in peb-1(cu9) mutants;
      however, g1 gland cell expression of a kel-1Colon, two colonsgfp reporter was
      reduced. As g1 gland cells have prominent functions during molting, we suggest
      defective gland cell differentiation contributes to peb-1(cu9) molting defects.
      In comparison, other peb-1 mutant phenotypes, including hindgut abnormalities,
      appeared independent of the molting defect. Similar phenotypes resulted from late
      loss of pha-4 function, suggesting that PEB-1 and PHA-4 have common functions in
      some tissues where they are co-expressed.

PMID- 15581871
TI  - Mother-daughter precursor cell fate transformation after Cdc2 down-regulation in
      the Drosophila bristle lineage.
AB  - The Drosophila bristle lineage is an excellent system in which to study how cell
      cycle and fate determination are synchronized in invariant cell lineages. In this
      model, five different cells arise from a single precursor cell, pI, after four
      asymmetric cell divisions. Cell diversity is achieved by the asymmetric
      segregation of cell determinants, such as Numb and Neuralized (Neur), resulting
      in differential activation of the Notch (N) pathway. We show that down-regulation
      of Cdc2, by over-expressing Tribbles, Dwee1, and Dmyt1 (three negative regulators
      of Cdc2) or by using thermo-sensitive Cdc2 mutant flies, delayed pI mitosis, and
      altered the polarity and the number of subsequent cell divisions. These
      modifications were associated with a mother-daughter cell fate transformation as
      the pI cell acquired the identity of the secondary precursor cell, pIIb. This
      type of change in cell identity only occurred when the N signaling pathway was
      inactive since ectopic N signaling transformed pI to pIIa-progeny fate. These
      transformations in cell identity suggest that, although synchronized, cell cycle
      and fate determination are independent phenomena in the bristle lineage.

PMID- 15581872
TI  - dPak is required for integrity of the leading edge cytoskeleton during Drosophila
      dorsal closure but does not signal through the JNK cascade.
AB  - The Pak kinases are effectors for the small GTPases Rac and Cdc42 and are divided
      into two subfamilies. Group I Paks possess an autoinhibitory domain that can
      suppress their kinase activity in trans. In Drosophila, two Group I kinases have
      been identified, dPak and Pak3. Rac and Cdc42 participate in dorsal closure of
      the embryo, a process in which a hole in the dorsal epidermis is sealed through
      migration of the epidermal flanks over a tissue called the amnioserosa. Dorsal
      closure is driven in part by an actomyosin contractile apparatus at the leading
      edge of the epidermis, and is regulated by a Jun amino terminal kinase (JNK)
      cascade. Impairment of dPak function using either loss-of-function mutations or
      expression of a transgene encoding the autoinhibitory domain of dPak led to
      disruption of the leading edge cytoskeleton and defects in dorsal closure but did
      not affect the JNK cascade. Group I Pak kinase activity in the amnioserosa is
      required for correct morphogenesis of the epidermis, and may be a component of
      the signaling known to occur between these two tissues. We conclude that dorsal
      closure requires Group I Pak function in both the amnioserosa and the epidermis.

PMID- 15581873
TI  - Otopetrin 1 is required for otolith formation in the zebrafish Danio rerio.
AB  - Orientation with respect to gravity is essential for the survival of complex
      organisms. The gravity receptor is one of the phylogenetically oldest sensory
      systems, and special adaptations that enhance sensitivity to gravity are highly
      conserved. The fish inner ear contains three large extracellular biomineral
      particles, otoliths, which have evolved to transduce the force of gravity into
      neuronal signals. Mammalian ears contain thousands of small particles called
      otoconia that serve a similar function. Loss or displacement of these structures
      can be lethal for fish and is responsible for benign paroxysmal positional
      vertigo (BPPV) in humans. The distinct morphologies of otoconial particles and
      otoliths suggest divergent developmental mechanisms. Mutations in a novel gene
      Otopetrin 1 (Otop1), encoding multi-transmembrane domain protein, result in
      nonsyndromic otoconial agenesis and a severe balance disorder in mice. Here we
      show that the zebrafish, Danio rerio, contains a highly conserved gene, otop1,
      that is essential for otolith formation. Morpholino-mediated knockdown of
      zebrafish Otop1 leads to otolith agenesis without affecting the sensory
      epithelium or other structures within the inner ear. Despite lack of otoliths in
      early development, otolith formation partially recovers in some fish after 2
      days. However, the otoliths are malformed, misplaced, lack an organic matrix, and
      often consist of inorganic calcite crystals. These studies demonstrate that Otop1
      has an essential and conserved role in the timing of formation and the size and
      shape of the developing otolith.

PMID- 15581874
TI  - Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud.
AB  - Fibroblast growth receptors (FGFRs) consist of four signaling family members.
      Mice with deletions of fgfr1 or fgfr2 are embryonic lethal prior to the onset of
      kidney development. To determine roles of FGFR1 and FGFR2 in the ureteric bud, we
      used a conditional targeting approach. First, we generated transgenic mice using
      the Hoxb7 promoter to drive cre recombinase and green fluorescent protein
      expression throughout ureteric bud tissue. We crossed Hoxb7creEGFP mice with mice
      carrying lox-p sites flanking critical regions of fgfr1 and/or fgfr2. Absence of
      fgfr1 from the ureteric bud (fgfr1(UB-/-)) results in no apparent renal
      abnormalities. In contrast, fgfr2(UB-/-) mice have very aberrant ureteric bud
      branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2(UB-/-)
      ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced
      proliferation. The nephrogenic mesenchymal lineage in fgfr2(UB-/-) mice develops
      normal-appearing glomeruli and tubules, and only slightly fewer nephrons than
      controls. In contrast, fgfr2(UB-/-) kidneys have abnormally thickened subcapsular
      cortical stromal mesenchyme. Ultimately, fgfr2(UB-/-) adult kidneys are small and
      abnormally shaped or are hydronephrotic. Finally, there are no additional
      abnormalities in the fgfr1/2(UB-/-) kidneys versus the fgfr2(UB-/-) kidneys. In
      conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching
      morphogenesis and stromal mesenchyme patterning.

PMID- 15581875
TI  - Integrin alpha4beta1 function is required for cell survival in developing retina.
AB  - In the retina, integrins in the beta1 family have been shown to be important in
      many phases of neuronal development, particularly neuroblast migration and axon
      outgrowth. However, the functions of specific integrin heterodimers are not well
      defined. In this study, we investigated the functions of beta1 integrins in
      developing chicken retina by expression of a dominant-negative beta1A construct
      using a replication-competent retrovirus. Inhibition of integrins using this
      approach resulted in alteration of cell morphology and increased apoptosis, but
      did not preclude migration and axon elongation. In an attempt to identify which
      specific beta1 heterodimer was important, expression and function of the
      alpha4beta1 heterodimer were also investigated. At early developmental stages,
      alpha4 protein and mRNA were detected in undifferentiated neuroblasts throughout
      the retina. At later stages, expression was confined to retinal ganglion cells
      (RGCs) and amacrine cells. A small molecule antagonist of alpha4 integrins was
      shown to inhibit neurite outgrowth on recombinant soluble vascular cell adhesion
      molecule-1 (VCAM-1), a known ligand of alpha4beta1. Introduction of alpha4
      antagonist in vivo gave rise to increased apoptosis and led to a thinning of the
      retina and reduced numbers of retinal ganglion cells (RGCs). We conclude that the
      integrin alpha4beta1 is important for survival of developing retinal neurons,
      including RGCs.

PMID- 15581876
TI  - Wnt4 is required for proper male as well as female sexual development.
AB  - Genes previously implicated in mammalian sexual development have either a male-
      or female-specific role. The signaling molecule WNT4 has been shown to be
      important in female sexual development. Lack of Wnt4 gives rise to
      masculinization of the XX gonad and we showed previously that the role of WNT4
      was to inhibit endothelial and steroidogenic cell migration into the developing
      ovary. Here we show that Wnt4 also has a function in the male gonad. We find that
      Sertoli cell differentiation is compromised in Wnt4 mutant testes and that this
      defect occurs downstream of the testis-determining gene Sry but upstream of Sox9
      and Dhh, two early Sertoli cell markers. Genetic analysis shows that this
      phenotype is primarily due to the action of WNT4 within the early genital ridge.
      Analysis of different markers identifies the most striking difference in the
      genital ridge at early stages of its development between wild-type and Wnt4
      mutant embryos to be a significant increase of steroidogenic cells in the Wnt4 -/
      gonad. These results identify WNT4 as a new factor involved in the mammalian
      testis determination pathway and show that genes can have a specific but distinct
      role in both male and female gonad development.

PMID- 15581877
TI  - A mutation in serca underlies motility dysfunction in accordion zebrafish.
AB  - Zebrafish acquire the ability for fast swimming early in development. The
      motility mutant accordion (acc) undergoes exaggerated and prolonged contractions
      on both sides of the body, interfering with the acquisition of patterned swimming
      responses. Our whole cell recordings from muscle indicate that the defect is not
      manifested in neuromuscular transmission. However, imaging of skeletal muscle of
      larval acc reveals greatly prolonged calcium transients and associated
      contractions in response to depolarization. Positional cloning of acc identified
      a serca mutation as the cause of the acc phenotype. SERCA is a sarcoplasmic
      reticulum transmembrane protein in skeletal muscle that mediates calcium re
      uptake from the myoplasm. The mutation in SERCA, a serine to phenylalanine
      substitution, is likely to result in compromised protein function that accounts
      for the observed phenotype. Indeed, direct evidence that mutant SERCA causes the
      motility dysfunction was provided by the finding that wild type fish injected
      with an antisense morpholino directed against serca, exhibited accordion-like
      contractions and impaired swimming. We conclude that the motility dysfunction in
      embryonic and larval accordion zebrafish stems directly from defective calcium
      transport in skeletal muscle rather than defective CNS drive.

PMID- 15581878
TI  - Activation of multidrug efflux transporter activity at fertilization in sea
      urchin embryos (Strongylocentrotus purpuratus).
AB  - This study presents functional and molecular evidence for acquisition of
      multidrug transporter-mediated efflux activity as a consequence of fertilization
      in the sea urchin. Sea urchin eggs and embryos express low levels of efflux
      transporter genes with homology to the multidrug resistance associated protein
      (mrp) and permeability glycoprotein (p-gp) families of ABC transporters. The
      corresponding efflux activity is low in unfertilized eggs but is dramatically
      upregulated within 25 min of fertilization; the expression of this activity does
      not involve de novo gene expression and is insensitive to inhibitors of
      transcription and translation indicating activation of pre-existing transporter
      protein. Our study, using specific inhibitors of efflux transporters, indicates
      that the major activity is from one or more mrp-like transporters. The expression
      of activity at fertilization requires microfilaments, suggesting that the
      transporters are in vesicles and moved to the surface after fertilization.
      Pharmacological inhibition of mrp-mediated efflux activity with MK571 sensitizes
      embryos to the toxic compound vinblastine, confirming that one role for the
      efflux transport activity is embryo protection from xenobiotics. In addition,
      inhibition of mrp activity with MK571 alone retards mitosis indicating that mrp
      like activity may also be required for early cell divisions.

PMID- 15581879
TI  - An integrated regulatory network controlling survival and migration in thyroid
      organogenesis.
AB  - The thyroid gland originates from the ventral floor of the foregut as a
      thickening of the endodermal cell layer. The molecular mechanisms underlying the
      early steps of thyroid morphogenesis are not known. Gene targeting experiments
      have contributed to the identification of several transcription factors, in
      general playing a role in the proliferation, survival, and migration of the
      thyroid cell precursors. The experiments reported here analyze the expression of
      the transcription factors Titf1, Hhex, Pax8, and Foxe1 in the thyroid primordium
      of null mutants of each of them. We found that most of these transcription
      factors are linked in an integrated regulatory network, each of them controlling
      the presence of other members of the network. The expression of Foxe1 is
      regulated in an intriguing fashion as it is strongly dependent on the presence of
      Pax8 in thyroid precursor cells, while the expression of the same gene in the
      pharyngeal endoderm surrounding the primordium is dependent on Sonic hedgehog
      (Shh)-derived signaling. Moreover, by the generation of mouse mutants expressing
      Foxe1 exclusively in the thyroid primordium, we provide a better understanding of
      the role of Foxe1 in these cells in order to acquire the competence to migrate
      into the underlying mesenchyme. In conclusion, we provide the first evidence of
      gene expression programs, controlled by a hierarchy of transcription factors
      expressed in the thyroid presumptive gut domain and directing the progression of
      thyroid morphogenesis.

PMID- 15581880
TI  - Dissection of cis-regulatory elements in the C. elegans Hox gene egl-5 promoter.
AB  - Hox genes are highly conserved segmental identity genes well known for their
      complex expression patterns and divergent targets. Here we present an analysis of
      cis-regulatory elements in the Caenorhabditis elegans Hox gene egl-5, which is
      expressed in multiple tissues in the posterior region of the nematode. We have
      utilized phylogenetic footprinting to efficiently identify cis-regulatory
      elements and have characterized these with gfp reporters and tissue-specific
      rescue experiments. We have found that the complex expression pattern of egl-5 is
      the cumulative result of the activities of multiple tissue or local region
      specific activator sequences that are conserved both in sequence and near-perfect
      order in the related nematode Caenorhabditis briggsae. Two conserved regulatory
      blocks analyzed in detail contain multiple sites for both positively and
      negatively acting factors. One of these regions may promote activation of egl-5
      in certain cells via the Wnt pathway. Positively acting regions are repressed in
      inappropriate tissues by additional negative pathways acting at other sites
      within the promoter. Our analysis has allowed us to implicate several new
      regulatory factors significant to the control of egl-5 expression.

PMID- 15581881
TI  - Identification of lineage-specific zygotic transcripts in early Caenorhabditis
      elegans embryos.
AB  - During Caenorhabditis elegans embryogenesis, a maternally supplied transcription
      factor, SKN-1, is required for the specification of the mesendodermal precursor,
      EMS, in the 4-cell stage embryo. When EMS divides, it gives rise to a mesoderm
      restricted precursor, MS, and an endoderm-restricted precursor, E. To
      systematically identify genes that function as key regulators of MS and/or E
      derived tissues, we identified, by microarray analyses, genes that are newly
      transcribed within a short developmental window (approximately 30 min)
      encompassing the generation and fate specification of the MS and E blastomeres.
      By comparing total cDNAs generated from individual, carefully staged embryos, we
      identified 275 genes up-regulated in 12-cell embryos compared to 4-cell embryos.
      Fifty of these 275 genes are down-regulated in 12-cell skn-1 mutant embryos and
      are designated skn-1-dependent zygotic (sdz) genes. The spatial and temporal
      expression patterns in C. elegans embryos of 10 randomly selected sdz genes were
      analyzed by a nuclear GFP reporter driven by the endogenous 5' regulatory
      sequence of each gene. GFP expression, although absent at the 4-cell stage, was
      detected at the 12- to 16-cell stage for all 10 genes and was restricted to EMS
      derived lineages for 7 of the 10. Among the seven lineage-specific genes, three
      genes are expressed equally in both MS and E lineages, two are expressed
      exclusively or predominantly in the MS lineage, and two are expressed exclusively
      in the E lineage. Depletion of skn-1 by RNAi abolishes the expression of all
      seven reporter transgenes in vivo, confirming that these genes are indeed skn-1
      dependent. These results demonstrate the successful combination of single-staged
      embryo cDNAs, genetic mutants, and whole transcriptome microarray analysis to
      identify stage- and lineage-specific transcripts in early C. elegans embryos.

PMID- 15581882
TI  - Zebrafish gcm2 is required for gill filament budding from pharyngeal ectoderm.
AB  - The pharyngeal arches give rise to multiple organs critical for diverse
      processes, including the thymus, thyroid and parathyroids. Several molecular
      regulators of thymus and thyroid organogenesis are strikingly conserved between
      mammals and zebrafish. However, land animals have parathyroids whereas fish have
      gills. The murine transcription factor Glial cells missing 2 (Gcm2) is expressed
      specifically in the parathyroid primordium in the endodermal epithelium of the
      third pharyngeal pouch, and in both mice and humans is required for normal
      development of parathyroid glands. The molecular regulation of fish gill
      organogenesis remains to be described. We report the expression of gcm2 in the
      zebrafish pharyngeal epithelium and a requirement for Hox group 3 paralogs for
      gcm2 expression. Strikingly, zebrafish gcm2 is expressed in the ectodermal
      portion of the pharyngeal epithelium and is required for the development of the
      gill filament buds, precursors of fish-specific gill filaments. This study
      identifies yet another role for a GCM gene in embryonic development and indicates
      a role for gcm2 during the evolution of divergent pharyngeal morphologies.

PMID- 15581883
TI  - dlx3b and dlx4b function in the development of Rohon-Beard sensory neurons and
      trigeminal placode in the zebrafish neurula.
AB  - Rohon-Beard sensory neurons, neural crest cells, and sensory placodes can be
      distinguished at the boundary of the embryonic epidermis (skin) and the neural
      plate. The inductive signals at the neural plate border region are likely to
      involve a gradient of bone morphogenic protein (BMP) in conjunction with FGF and
      Wnts and other signals. However, how these signals are transduced to produce the
      final cell fate remains to be determined. Recent evidence from Xenopus and chick
      suggest that Dlx genes are required for the generation of cell fates at the
      neural plate border (McLarren, K.W., Litsiou, A., Streit, A., 2003. DLX5
      positions the neural crest and preplacode region at the border of the neural
      plate. Dev. Biol. 259, 34-47; Woda, J.M., Pastagia, J., Mercola, M., Artinger,
      K.B., 2003. Dlx proteins position the neural plate border and determine adjacent
      cell fates. Development 130, 331-342). In the present study, we extend these
      findings to zebrafish, where we unequivocally demonstrate that dlx3b and dlx4b
      function in a dose-dependent manner to specify cell fates such as Rohon-Beard
      sensory neurons and trigeminal sensory placodes. dlx function was examined by
      inhibiting: (1) protein levels with antisense morpholino oligonucleotides (MOs),
      and (2) activity by repressing the ability of dlx-homeodomain to bind to
      downstream targets (EnR-dlx3bhd mRNA; dlx3b homeodomain fused to Engrailed
      transcriptional repressor domain). Inhibition of dlx3b and dlx4b protein and
      activity resulted in the reduction or complete loss of Rohon-Beard (RB) sensory
      neurons and trigeminal (TG) sensory placodes. These data suggest that dlx3b and
      dlx4b function in the specification of RB neurons and trigeminal sensory placodes
      in zebrafish. Further, we have shown that dlx3b and dlx4b function in a non-cell
      autonomous manner for RB neuron development; dlx3b and dlx4b act to regulate
      bmp2b expression at the non-neural ectodermal border. These data suggest that the
      contribution of dlx3b and dlx4b to neural plate border formation is partially non
      cell-autonomous acting via BMP activity.

PMID- 15581884
TI  - Groucho-dependent repression by sloppy-paired 1 differentially positions anterior
      pair-rule stripes in the Drosophila embryo.
AB  - The Drosophila body plan is composed of a linear array of cephalic, thoracic, and
      abdominal segments along the anterior posterior axis. The number and positions of
      individual segments are established by a transcriptional network comprised of
      maternal effect, gap, pair-rule, and segment polarity genes. The sloppy-paired
      (slp) locus contains two genes (slp1 and slp2) that are expressed in overlapping
      striped patterns in the presumptive thorax and abdomen. Previous studies suggest
      that these genes function at the pair-rule and segment polarity levels to
      establish the spacing and polarity of thoracic and abdominal segments. One of
      these genes (slp1) is also expressed in a broad anterior domain that appears
      before the striped patterns. There are severe cephalic defects in slp1 mutants,
      including the complete loss of the mandibular segment, but the molecular roles
      played by Slp1 in anterior patterning are not clear. Here, we present evidence
      that the anterior Slp1 domain acts as a gradient to differentially repress the
      anteriormost stripes of several different pair-rule genes. This repressive
      gradient contributes to the precise spatial arrangement of anterior pair-rule
      stripe borders required for expression of the first engrailed stripe and the
      formation of the mandibular segment. These results suggest that Slp1 functions as
      a gap gene-like repressor, in addition to its roles at the pair-rule and segment
      polarity levels of the hierarchy. The Slp1 protein contains a protein motif (EH1)
      which mediates binding to the transcriptional corepressor Groucho (Gro). We show
      that this domain is required for Slp1-mediated repression in vivo.

PMID- 15581885
TI  - Regulation of hhex expression in the yolk syncytial layer, the potential
      Nieuwkoop center homolog in zebrafish.
AB  - The Nieuwkoop center is the earliest signaling center during dorsal-ventral
      pattern formation in amphibian embryos and has been implied to function in
      induction of the Spemann-Mangold organizer. In zebrafish, Nieuwkoop-center-like
      activity resides in the dorsal yolk syncytial layer (YSL) at the interface of the
      vegetal yolk cell and the blastoderm. hex homologs are expressed in the anterior
      endomesoderm in frogs (Xhex), the anterior visceral endoderm in mice, and the
      dorsal YSL in zebrafish (hhex). Here, we investigate the control of hhex
      expression in the YSL. We demonstrate that bozozok (boz) is absolutely required
      for early hhex expression, while overexpression of boz causes ectopic hhex
      expression. Activation of Wnt/beta-catenin signaling by LiCl induces hhex
      expression in wild-type YSL but not in boz mutant embryos, revealing that boz
      activity is required downstream of Wnt/beta-catenin signaling for hhex
      expression. Further, we show that the boz-mediated induction of hhex is
      independent of the Boz-mediated repression of bmp2b. Our data reveal that
      repressive effects of both Vega1 and Vega2 may be responsible for the exclusion
      of hhex expression from the ventral and lateral parts of the YSL. In summary,
      zebrafish hhex appears to be activated by Wnt/beta-catenin in the dorsal YSL,
      where Boz acts in a permissive way to limit repression of hhex by Vega1 and
      Vega2.

PMID- 15581886
TI  - Computational discovery of DNA motifs associated with cell type-specific gene
      expression in Ciona.
AB  - Temporally and spatially co-expressed genes are expected to be regulated by
      common transcription factors and therefore to share cis-regulatory elements. In
      the ascidian Ciona intestinalis, the whole-genome sequences and genome-scale gene
      expression profiles allow the use of computational techniques to investigate cis
      elements that control transcription. We collected 5' flanking sequences of 50
      tissue-specific genes from genome databases of C. intestinalis and a closely
      related species Ciona savignyi. We searched for DNA motifs over-represented in
      upstream regions of a group of co-expressed genes. Several motifs were
      distributed predominantly in upstream regions of photoreceptor, pan-neuronal, or
      muscle-specific gene groups. One muscle-specific motif, M2, was distributed
      preferentially in regions from -200 to -100 bp relative to the translational
      start sites. Promoters of muscle-specific genes of C. intestinalis were isolated,
      connected with a green fluorescent protein gene (GFP), and introduced into C.
      intestinalis embryos. In muscle cells, these promoters specifically drove GFP
      expression, which mutations of the M2 sites greatly reduced. When M2 sites were
      located upstream of a basal promoter, the reporter GFP was specifically expressed
      in muscle cells. These results suggest the validity of our computational
      prediction of cis-regulatory elements. Thus, bioinformatics can help identify cis
      regulatory elements involved in chordate development.

PMID- 15581887
TI  - Structure of Ca2+ release channel at 14 A resolution.
AB  - The 14 A resolution structure of the 2.3 MDa Ca2+ release channel (also known as
      RyR1) was determined by electron cryomicroscopy and single particle
      reconstruction. This structure was produced using collected data used for our
      previous published structures at 22-30 A resolution, but now taking advantage of
      recent algorithmic improvements in the EMAN software suite. This improved map
      clearly exhibits more structural detail and allows better defined docking of
      computationally predicted structural domain folds. Using sequence-based fold
      recognition, the N-terminal region of RyR1, residues 216-572, was predicted to
      have significant structural similarity with the IP3-binding core region of the
      type 1 IP3R. This putative structure was computationally localized to the clamp
      shaped region of RyR1, which has been implicated to have a regulatory role in the
      channel activity.

PMID- 15581888
TI  - Supramolecular assemblies of human frataxin are formed via subunit-subunit
      interactions mediated by a non-conserved amino-terminal region.
AB  - The mitochondrial protein frataxin is emerging as a novel mechanism to promote
      iron metabolism while also providing anti-oxidant protection. Recombinant
      frataxin proteins from different species are able to form large molecular
      assemblies that store Fe(III) as a stable mineral in vitro. Furthermore,
      monomeric and assembled forms of frataxin donate Fe(II) to the Fe-S cluster
      scaffold protein IscU, [3Fe-4S]1+ aconitase, and ferrochelatase in vitro.
      However, little is known about the speciation of frataxin in vivo, and the
      physiologically relevant form(s) of the protein remains undefined. Here, we
      report that human heart mitochondria contain frataxin species of increasing
      negative surface charge and molecular mass, ranging from monomer to polymers of
      >1 MDa. Moreover, we show that the main partner protein of frataxin, IscU, binds
      in a stable manner to frataxin oligomers. These results suggest that assembly is
      a physiologic property of frataxin. Biochemical analyses further reveal that,
      unlike the prokaryotic and yeast frataxin homologues, which require iron-protein
      interactions for assembly, human frataxin uses stable subunit-subunit
      interactions involving a non-conserved amino-terminal region. We propose that
      human frataxin is a modular protein that depends on self-assembly to accomplish
      its diverse functions.

PMID- 15581889
TI  - Fixed conformation nucleoside analogs effectively inhibit excision-proficient HIV
      1 reverse transcriptases.
AB  - An important mechanism of resistance to nucleoside analogs is the enhanced
      excision of the analog after it has been incorporated. Excision requires that the
      analog be located at the 3' terminus of the primer. We have developed nucleoside
      analogs that do not block DNA synthesis at the point of incorporation, but only
      after additional normal dNTPs have been added to the DNA. Such "delayed chain
      terminators" should be relatively resistant to excision and therefore effective
      against drug-resistant HIV-1 reverse transcriptases (RTs) that are proficient at
      excision. We tested a class of nucleoside analogs in which a pseudosugar ring is
      locked in either the North or the South conformation. These analogs have a 3' OH
      present on the pseudosugar ring, which allows extension of the primer strand
      after the analog is incorporated. We asked whether these analogs would inhibit
      polymerization by HIV-1 RT in assays using purified HIV-1 RT and in cell-based
      assays. HIV-1 RT did not effectively incorporate the analogs in which the
      pseudosugar is in the South conformation. The North conformation analogs are
      readily incorporated into the primer; the primer can be extended for two or three
      additional nucleotides before extension is inhibited. This block to
      polymerization is not complete; larger extension products are detectable at
      longer incubation times. Experiments with purified excision-proficient HIV-1 RT
      mutants suggest that the North conformation analogs are relatively resistant to
      excision. These analogs can also block the replication of viruses containing
      excision-proficient RTs. Although the fixed-conformation nucleotides are probably
      not suitable for development as drugs, other nucleoside analogs that cause
      delayed chain termination may complement the nucleoside analogs already approved
      for HIV-1 therapy.

PMID- 15581890
TI  - Monitoring sequence space as a test for the target of selection in viruses.
AB  - An essential feature of viral quasispecies, predicted from quasispecies theory,
      is that the target of selection is the mutant distribution as a whole. To test
      molecularly the mutant composition selected from a viral quasispecies we
      reconstructed a mutant distribution using 19 antigenic variants of foot-and-mouth
      disease virus (FMDV). Each variant was marked by a specific amino acid
      replacement at a major antigenic site of the virus that conferred resistance to a
      monoclonal antibody (mAb). The variants were introduced in the mutant spectrum of
      a biological FMDV clone, at a frequency commonly found in FMDV quasispecies. The
      reconstructed quasispecies (and a number of control populations) were allowed to
      replicate in the presence or absence of the mAb. The mutant distribution that
      became dominant as a result of antibody selection included at least ten of the 19
      mutants initially used to reconstruct the quasispecies. No such biased mutant
      repertoire was found in control populations. The results show that a mutant
      distribution was selected, and are incompatible with selection of an individual
      genome, which then generated multiple mutants upon further replication. An ample
      representation of variants immediately following a selection event should
      contribute to subsequent adaptability of the virus.

PMID- 15581891
TI  - Putative autocleavage of reovirus mu1 protein in concert with outer-capsid
      disassembly and activation for membrane permeabilization.
AB  - Capsid proteins of several different families of non-enveloped animal viruses
      with single-stranded RNA genomes undergo autocatalytic cleavage (autocleavage) as
      a maturation step in assembly. Similarly, the 76 kDa major outer-capsid protein
      mu1 of mammalian orthoreoviruses (reoviruses), which are non-enveloped and have
      double-stranded RNA genomes, undergoes putative autocleavage between residues 42
      and 43, yielding N-terminal N-myristoylated fragment mu1N and C-terminal fragment
      mu1C. Cleavage at this site allows release of mu1N, which is thought to be
      critical for penetration of the host-cell membrane during cell entry. Most
      previous studies have suggested that cleavage at the mu1N/mu1C junction precedes
      addition to the outer capsid during virion assembly, such that only a small
      number of the mu1 subunits in mature virions remain uncleaved at that site
      (approximately 5%). In this study, we varied the conditions for disruption of
      virions before running the proteins on denaturing gels and in several
      circumstances recovered much higher levels of uncleaved mu1 (up to approximately
      60%). Elements of the disruption conditions that allowed greater recovery of
      uncleaved protein were increased pH, absence of reducing agent, and decreased
      temperature. These same elements allowed comparably higher levels of the mu1delta
      protein, in which cleavage at the mu1N/delta junction has not occurred, to be
      recovered from particle uncoating intermediates in which mu1 had been previously
      cleaved by chymotrypsin in a distinct protease-sensitive region near residue 580.
      The capacity to recover higher levels of mu1delta following disruption of these
      particles for electrophoresis was lost, however, in concert with a series of
      structural changes that activate the particles for membrane permeabilization,
      suggesting that the putative autocleavage is itself one of these changes.

PMID- 15581892
TI  - Non-equivalent interactions between amino-terminal domains of neighboring lambda
      integrase protomers direct Holliday junction resolution.
AB  - The bacteriophage lambda site-specific recombinase (Int), in contrast to other
      family members such as Cre and Flp, has an amino-terminal domain that binds "arm
      type" DNA sequences different and distant from those involved in strand exchange.
      This defining feature of the heterobivalent recombinases confers a directionality
      and regulation that is unique among all recombination pathways. We show that the
      amino-terminal domain is not a simple "accessory" element, as originally thought,
      but rather is incorporated into the core of the recombination mechanism, where it
      is well positioned to exert its profound effects. The results reveal an
      unexpected pattern of intermolecular interactions between the amino-terminal
      domain of one protomer and the linker region of its neighbor within the
      tetrameric Int complex and provide insights into those features distinguishing an
      "active" from an "inactive" pair of Ints during Holliday junction resolution.

PMID- 15581893
TI  - Acyl-CoA oxidase 1 from Arabidopsis thaliana. Structure of a key enzyme in plant
      lipid metabolism.
AB  - The peroxisomal acyl-CoA oxidase family plays an essential role in lipid
      metabolism by catalyzing the conversion of acyl-CoA into trans-2-enoyl-CoA during
      fatty acid beta-oxidation. Here, we report the X-ray structure of the FAD
      containing Arabidopsis thaliana acyl-CoA oxidase 1 (ACX1), the first three
      dimensional structure of a plant acyl-CoA oxidase. Like other acyl-CoA oxidases,
      the enzyme is a dimer and it has a fold resembling that of mammalian acyl-CoA
      oxidase. A comparative analysis including mammalian acyl-CoA oxidase and the
      related tetrameric mitochondrial acyl-CoA dehydrogenases reveals a substrate
      binding architecture that explains the observed preference for long-chained, mono
      unsaturated substrates in ACX1. Two anions are found at the ACX1 dimer interface
      and for the first time the presence of a disulfide bridge in a peroxisomal
      protein has been observed. The functional differences between the peroxisomal
      acyl-CoA oxidases and the mitochondrial acyl-CoA dehydrogenases are attributed to
      structural differences in the FAD environments.

PMID- 15581894
TI  - Role of the N terminus in enzyme activity, stability and specificity in
      thermophilic esterases belonging to the HSL family.
AB  - A superposition between the structures of Alicyclobacillus acidocaldarius
      esterase 2 (EST2) and Burkholderia cepacia lipase, the latter complexed with a
      phosphonate inhibitor, allowed us to hypothesize for the EST2 N terminus a role
      in restricting the access to the active site and therefore in modulating
      substrate specificity. In order to test this hypothesis we generated by site
      directed mutagenesis some truncated versions of EST2 and its double mutant
      M211S/R215L (S/L) at the N terminus. In parallel, an analysis of the Sulfolobus
      solfataricus P2 genome allowed us to identify a gene coding for a putative
      esterase of the HSL family having a natural deletion of the corresponding region.
      The product of this gene and the above-mentioned EST2 mutants were expressed in
      Escherichia coli, purified and characterised. These studies support the notion
      that the N terminus affects substrate specificity other than several other enzyme
      parameters. Although the deletions afforded a tenfold and 550-fold decrease in
      catalytic efficiency towards the best substrate pNP-hexanoate at 50 degrees C for
      EST2 and S/L, respectively, the analysis of the specific activities with
      different triacylglycerols with respect to pNP-hexanoate showed that their ratios
      were higher for deleted versus non-deleted enzymes, on all tested substrates. In
      particular, the above ratios for glyceryl tridecanoate were 30-fold and 14-fold
      higher in S/L and EST2 deleted forms, respectively, compared with their full
      length versions. This behaviour was confirmed by the analysis of the
      S.solfataricus esterase, which showed similar specific activities on pNP
      hexanoate and triacylglycerols; in addition, higher activities on the latter
      substrates were observed in comparison with EST2, S/L and their deleted forms.
      Finally, a dramatic effect on thermophilicity and thermostability in the EST2
      deleted forms was observed. This is the first report highlighting the importance
      of the "cap" domain in the HSL family, since the N terminus partly contributes to
      the building up of this structure.

PMID- 15581895
TI  - ATP synthase from Saccharomyces cerevisiae: location of subunit h in the
      peripheral stalk region.
AB  - Subunit h is a component of the peripheral stalk region of ATP synthase from
      Saccharomyces cerevisiae. It is weakly homologous to subunit F6 in the bovine
      enzyme, and F6 can replace the function of subunit h in a yeast strain from which
      the gene for subunit h has been deleted. The removal of subunit h (or F6)
      uncouples ATP synthesis from the proton motive force. A biotinylation signal has
      been introduced following the C terminus of subunit h. It becomes biotinylated in
      vivo, and allows avidin to be bound quantitatively to the purified enzyme complex
      in vitro. By electron microscopy of the ATP synthase-avidin complex in negative
      stain and by subsequent image analysis, the C terminus of subunit h has been
      located in a region of the peripheral stalk that is close to the Fo membrane
      domain of ATP synthase. Models of the peripheral stalk are proposed that are
      consistent with this location and with reconstitution experiments conducted with
      isolated peripheral stalk subunits.

PMID- 15581896
TI  - Crystal structures of complexes between the R61 DD-peptidase and peptidoglycan
      mimetic beta-lactams: a non-covalent complex with a "perfect penicillin".
AB  - The bacterial D-alanyl-D-alanine transpeptidases (DD-peptidases) are the killing
      targets of beta-lactams, the most important clinical defense against bacterial
      infections. However, due to the constant development of antibiotic-resistance
      mechanisms by bacteria, there is an ever-present need for new, more effective
      antimicrobial drugs. While enormous numbers of beta-lactam compounds have been
      tested for antibiotic activity in over 50 years of research, the success of a
      beta-lactam structure in terms of antibiotic activity remains unpredictable.
      Tipper and Strominger suggested long ago that beta-lactams inhibit DD-peptidases
      because they mimic the D-alanyl-D-alanine motif of the peptidoglycan substrate of
      these enzymes. They also predicted that beta-lactams having a peptidoglycan
      mimetic side-chain might be better antibiotics than their non-specific
      counterparts, but decades of research have not provided any evidence for this. We
      have recently described two such novel beta-lactams. The first is a penicillin
      having the glycyl-L-alpha-amino-epsilon-pimelyl side-chain of Streptomyces strain
      R61 peptidoglycan, making it the "perfect penicillin" for this organism. The
      other is a cephalosporin with the same side-chain. Here, we describe the X-ray
      crystal structures of the perfect penicillin in non-covalent and covalent
      complexes with the Streptomyces R61 DD-peptidase. The structure of the non
      covalent enzyme-inhibitor complex is the first such complex to be trapped
      crystallographically with a DD-peptidase. In addition, the covalent complex of
      the peptidyl-cephalosporin with the R61 DD-peptidase is described. Finally, two
      covalent complexes with the traditional beta-lactams benzylpenicillin and
      cephalosporin C were determined for comparison with the peptidyl beta-lactams.
      These structures, together with relevant kinetics data, support Tipper and
      Strominger's assertion that peptidoglycan-mimetic side-chains should improve beta
      lactams as inhibitors of DD-peptidases.

PMID- 15581897
TI  - Structure and function of the antibiotic resistance-mediating methyltransferase
      AviRb from Streptomyces viridochromogenes.
AB  - The emergence of antibiotic-resistant bacterial strains is a widespread problem
      in medical practice and drug design, and each case requires the elucidation of
      the underlying mechanism. AviRb from Streptomyces viridochromogenes methylates
      the 2'-O atom of U2479 of the 23S ribosomal RNA in Gram-positive bacteria and
      thus mediates resistance to the oligosaccharide (orthosomycin) antibiotic
      avilamycin. The structure of AviRb with and without bound cofactor S-adenosyl-L
      methionine (AdoMet) was determined, showing that it is a homodimer belonging to
      the SpoU family within the SPOUT class of methyltransferases. The relationships
      within this class were analyzed in detail and, in addition, a novel fourth SpoU
      sequence fingerprint is proposed. Each subunit of AviRb consists of two domains.
      The N-terminal domain, being related to the ribosomal proteins L30 and L7Ae, is
      likely to bind RNA. The C-terminal domain is related to all SPOUT
      methyltransferases, and is responsible for AdoMet-binding, catalysis and
      dimerization. The cofactor binds at the characteristic knot of the polypeptide in
      an unusually bent conformation. The transferred methyl group points to a broad
      cleft formed with the L30-type domain of the other subunit. Measurements of
      mutant activity revealed four important residues responsible for catalysis and
      allowed the modeling of a complex between AviRb and the RNA target. The model
      includes a specificity pocket for uracil but does not contain a base for
      deprotonating the 2'-O atom of U2479 on methylation.

PMID- 15581898
TI  - APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles.
AB  - APOBEC3G is a cytidine deaminase that limits the replication of many
      retroviruses. This antiviral host factor is packaged into retrovirus particles,
      where it targets single-stranded DNA generated during reverse transcription and
      induces up to 2% of G-to-A mutations, which are lethal for the HIV-1 provirus.
      Vif protein counteracts this antiviral factor by decreasing its packaging into
      lentivirus particles. Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin
      ligase, interacts with APOBEC3G, through its WW2 and WW3 domains. As a result of
      this interaction, APOBEC3G undergoes post-translational modification by addition
      of ubiquitin moieties. Accordingly, we demonstrate that the dominant negative
      Nedd4-1 C/S form prevents APOBEC3G ubiquitination. Moreover, the packaging of
      APOBEC3G into Pr55 Gag virus-like particles and into HIV-1 virions is reduced
      when Nedd4-1 C/S is expressed. During HIV-1 viral production in the presence of
      APOBEC3G, Nedd4-1 C/S restores partially the infectivity of Deltavif HIV-1. We
      conclude that the ubiquitination of APOBEC3G by Nedd4-1 favors its targeting to
      the virus assembly site where APOBEC3G interacts with Gag and is packaged into
      HIV-1 particles in the absence of Vif.

PMID- 15581899
TI  - Isocitrate dehydrogenase from the hyperthermophile Aeropyrum pernix: X-ray
      structure analysis of a ternary enzyme-substrate complex and thermal stability.
AB  - Isocitrate dehydrogenase from Aeropyrum pernix (ApIDH) is a homodimeric enzyme
      that belongs to the beta-decarboxylating dehydrogenase family and is the most
      thermostable IDH identified. It catalyzes the NADP+ and metal-dependent oxidative
      decarboxylation of isocitrate to alpha-ketoglutarate. We have solved the crystal
      structures of a native ApIDH at 2.2 A, a pseudo-native ApIDH at 2.1 A, and of
      ApIDH in complex with NADP+, Ca2+ and d-isocitrate at 2.3 A. The pseudo-native
      ApIDH is in complex with etheno-NADP+ which was located at the surface instead of
      in the active site revealing a novel adenine-nucleotide binding site in ApIDH.
      The native and the pseudo-native ApIDHs were found in an open conformation,
      whereas one of the subunits of the ternary complex was closed upon substrate
      binding. The closed subunit showed a domain rotation of 19 degrees compared to
      the open subunit. The binding of isocitrate in the closed subunit was identical
      with that of the binary complex of porcine mitochondrial IDH, whereas the binding
      of NADP+ was similar to that of the ternary complex of IDH from Escherichiacoli.
      The reaction mechanism is likely to be conserved in the different IDHs. A proton
      relay chain involving at least five solvent molecules, the 5'-phosphate group of
      the nicotinamide-ribose and a coupled lysine-tyrosine pair in the active site, is
      postulated as essential in both the initial and the final steps of the catalytic
      reaction of IDH. ApIDH was found to be highly homologous to the mesophilic IDHs
      and was subjected to a comparative analysis in order to find differences that
      could explain the large difference in thermostability. Mutational studies
      revealed that a disulfide bond at the N terminus and a seven-membered inter
      domain ionic network at the surface are major determinants for the higher
      thermostability of ApIDH compared to EcIDH. Furthermore, the total number of ion
      pairs was dramatically higher in ApIDH compared to the mesophilic IDHs if a
      cutoff of 4.2 A was used. A calculated net charge of only +1 compared to -19 and 
      25 in EcIDH and BsIDH, respectively, suggested a high degree of electrostatic
      optimization, which is known to be an important determinant for increased
      thermostability.

PMID- 15581900
TI  - Drosophila alcohol dehydrogenase: acetate-enzyme interactions and novel insights
      into the effects of electrostatics on catalysis.
AB  - Drosophila alcohol dehydrogenase (DADH) is an NAD+-dependent enzyme that
      catalyzes the oxidation of alcohols to aldehydes/ketones and that is also able to
      further oxidize aldehydes to their corresponding carboxylic acids. The structure
      of the ternary enzyme-NADH-acetate complex of the slow alleloform of Drosophila
      melanogaster ADH (DmADH-S) was solved at 1.6 A resolution by X-ray
      crystallography. The coenzyme stereochemistry of the aldehyde dismutation
      reaction showed that the obtained enzyme-NADH-acetate complex reflects a
      productive ternary complex although no enzymatic reaction occurs. The
      stereochemistry of the acetate binding in the bifurcated substrate-binding site,
      along with previous stereochemical studies of aldehyde reduction and alcohol
      oxidation shows that the methyl group of the aldehyde in the reduction reaction
      binds to the R1 and in the oxidation reaction to the R2 sub-site. NMR studies
      along with previous kinetic studies show that the formed acetaldehyde
      intermediate in the oxidation of ethanol to acetate leaves the substrate site
      prior to the reduced coenzyme, and then binds to the newly formed enzyme-NAD+
      complex. Here, we compare the three-dimensional structure of D.melanogaster ADH-S
      and a previous theoretically built model, evaluate the differences with the
      crystal structures of five Drosophila lebanonensis ADHs in numerous complexed
      forms that explain the substrate specificity as well as subtle kinetic
      differences between these two enzymes based on their crystal structures. We also
      re-examine the electrostatic influence of charged residues on the surface of the
      protein on the catalytic efficiency of the enzyme.

PMID- 15581901
TI  - Relation of enzyme activity to local/global stability of murine adenosine
      deaminase: 19F NMR studies.
AB  - Adenosine deaminase (ADA, EC 3.5.4.4) is a ubiquitous (beta/alpha)8-barrel enzyme
      crucial for purine metabolism and normal immune competence. In this study, it was
      observed that loss of enzyme activity of murine ADA (mADA) precedes the global
      secondary and tertiary structure transition when the protein is exposed to
      denaturant. The structural mechanism for this phenomenon was probed using site
      specific 19F NMR spectroscopy in combination with [6-19F]tryptophan labeling and
      inhibitor binding. There are four tryptophan residues in mADA and all are located
      more than 12 A from the catalytic site. The 19F NMR spectra of [6-19F]Trp
      labelled mADA show that the urea-induced chemical shift change of 19F resonance
      of W161, one of the four tryptophan 19F nuclei, correlates with the loss of
      enzyme activity. The urea-induced chemical shift change of another 19F resonance
      of W117 correlates with the change of the apparent rate constant for the binding
      of transition-state analogue inhibitor deoxycoformycin to the enzyme. On the
      other hand, the chemical environment of the local region around W264 does not
      change significantly, as a consequence of perturbation by low concentrations of
      urea or substrate analog. The results indicate that different regions of mADA
      have different local stability, which controls the activity and stability of the
      enzyme. The results provide new insights into the relationship between the
      function of a protein and its conformational flexibility as well as its global
      stability. This study illustrates the advantage of 19F NMR spectroscopy in
      probing site-related conformational change information in ligand binding,
      enzymatic activity and protein folding.

PMID- 15581902
TI  - Novel CalphaNN structural motif for protein recognition of phosphate ions.
AB  - Phosphate is one of the most frequently exploited chemical moieties in nature,
      present in a wide range of naturally occurring and critically important small
      molecules. Several phosphate group recognition motifs have been found for a few
      narrow groups of proteins, but for many protein families and folds the mode of
      phosphate recognition remains unclear. Here, we have analyzed the structures of
      all fold-representative protein-ligand complexes listed in the FSSP database,
      regardless of whether the bound ligand included a phosphate group. Based on a
      phosphate-binding motif that we identified in pyridoxal phosphate binding
      proteins, we have identified a new anion-binding structural motif, CalphaNN,
      common to 104 fold-representative protein structures that belong to 62 different
      folds, of which 86% of the fold-representative structures (51 folds) bind
      phosphate or lone sulfate ions. This motif leads to a precise mode for phosphate
      group recognition forming a structure where atoms of the phosphate group occupy
      the most favorable stabilizing positions. The anion-binding CalphaNN motif is
      based only on main-chain atoms from three adjacent residues, has a conservative
      betaalphaalpha or betaalphabeta geometry, and recognizes the free phosphate
      (sulfate) ion as well as one or more phosphate groups in nucleotides and in a
      variety of cofactors. Moreover, the CalphaNN motif is positioned in functionally
      important regions of protein structures and often residues of the motif directly
      participate in the function of the protein.

PMID- 15581903
TI  - Self-association of a small heat shock protein.
AB  - Human Hsp27 oligomerizes in vivo in a phosphorylation-dependent manner that
      regulates the functional activity of the protein. We have studied the self
      association of wild-type Hsp27 by both sedimentation velocity and sedimentation
      equilibrium analysis and established that the protein forms an equilibrium
      mixture of monomers/dimers, tetramers, 12-mers and 16-mers (20 mM Tris-HCl (pH
      8.4), 100 mM NaCl, 20 degrees C). Corresponding analysis of the S15D/S78D/S82D
      triple variant, which is believed to mimic the behavior of phosphorylated Hsp27,
      establishes that this form of the protein forms primarily monomers and dimers but
      also forms a small fraction of very large oligomers. Variants in which critical N
      terminal sequences have been deleted exhibit oligomerization behavior that is
      intermediate between that of the triple variant and the wild-type protein. On the
      other hand a C-terminal sequence deletion variant forms larger oligomers than
      does the wild-type protein, but also exhibits a greater fraction of smaller
      oligomers. Notably, the presence of an N-terminal His6-tag induces formation of
      much larger oligomers than observed for any other form of the protein. The
      results of this work establish that the wild-type protein forms smaller oligomers
      than previously believed, define the roles played by various structural domains
      in Hsp27 oligomerization, and provide improved molecular probes with better
      defined properties for the design of future experiments.

PMID- 15581904
TI  - Advanced glycation and endothelial functions: a link towards vascular
      complications in diabetes.
AB  - The formation of advanced glycation end-products (AGEs), also called the Maillard
      reaction, occurs ubiquitously and irreversibly in patients with diabetes
      mellitus, and its consequences are especially relevant to vascular dysfunctions.
      The interaction of AGEs with their receptors (RAGE) has been implicated in the
      development of vascular complications. This interaction elicits remarkable
      vascular cell changes analogous to those observed in diabetes mellitus, including
      angiogenic and thrombogenic responses of endothelial cells, increased oxidative
      stress, and functional alterations in vascular tone control. This review focuses
      on AGEs formation, the interaction with their specific receptors and how the
      triggered intracellular events determine functional alterations of vascular
      endothelium. Finally, some potential pharmacological approaches undertaken to
      circumvent the deleterious effects of AGEs are also discussed.

PMID- 15581905
TI  - Unliganded RXR acts as an inhibitory factor on troglitazone-induced activation.
AB  - Troglitazone (TZ), a thiazolidinedione derivative, is a specific ligand for the
      peroxisome proliferator-activated receptor (PPAR) gamma and improves insulin
      sensitivity. PPARgamma regulates the expression of genes by binding to PPAR
      response element in promoter regions of regulator genes as heterodimers with a
      retinoid X receptor (RXR). We report here that PPARgamma activation by TZ depends
      on the expression levels of RXR. A transient transfection study in CV-1 cells
      revealed that the activation by TZ was suppressed by increasing amounts of
      expression of RXR, but not PPARgamma. Northern blot analysis revealed that
      PPARgamma and RXR were not expressed in CV-1 cells, and TZ did not induce
      PPARgamma or RXR mRNA in CV-1 cells indicating that RXR suppression is not
      related to these endogenous receptor expressions. Electrophoretic mobility shift
      assay revealed that the increasing amount of RXR did not compete with the DNA
      binding of the PPARgamma/RXR heterodimer in the presence or absence of TZ.
      Transfected co-activators enhanced the TZ-dependent gene transcription, and this
      activation was inhibited by excessive amounts of RXR, indicating that unliganded
      RXR may recruit the specific coactivators from the PPARgamma/RXR heterodimer.

PMID- 15581906
TI  - Production of matrix metalloproteinases in specific subpopulations of human
      patient breast cancer invading in three dimensional culture system.
AB  - This article aims at investigating the effect of production of matrix
      metalloproteinases (MMP) in human breast cancer tissues by means of three
      dimensional culture system. Thirty-nine tumour samples were taken from breast
      cancer patients. The tumour blocks were cultured on sponge gel using the three
      dimensional culture system. Breast cancer cells began shedding into the culture
      medium after 24 hours of culture. The cells were stained with trypan blue dye to
      assess viability on days 2, 4, 6 and 8. The culture medium was collected at these
      time points and tested for matrix metalloproteinases (MMP) 1,2,3 and 9
      activities. There was a progressive increase in migration of cancer cells into
      the gel and culture medium from day 2 to day 8 and the interval difference was
      statistically significant (F ratio=4.06; p=0.008). The levels of all the MMPs
      tested were also significantly raised (P<0.05 for all the MMPs tested). When the
      levels of MMPs were correlated with the metabolic activities in the gel, medium
      and tumour block, cells in block show no correlation whereas cells in gel
      correlated significantly with MMP-1 and MMP-3. Cancer cells in the culture medium
      correlated with MMP-9. In conclusion, there is a progressive migration of cancer
      cells outside the tumour block. The migration into the gel and culture medium is
      associated with progressive and differential production of MMPs. It is likely
      that the three dimensional culture model assists in the selection of different
      subpopulations of cancer cells with different invasion properties as exemplified
      by the differential production of MMP.

PMID- 15581907
TI  - Neophobia and cortical and subcortical binding of the dopamine D2 receptor
      antagonist [3H]-raclopride.
AB  - The potential role of dopamine system in response to novelty was analysed using
      the selective dopamine D2 receptor antagonist, raclopride, in behavioral and
      biochemical assays, in rats (the open field test, and specific binding of [3H]
      raclopride, within different brain structures measured with autoradiography). It
      was found that raclopride at a low dose (50 microg/kg, IP) caused anxiolytic-like
      effect (increased the anti-thigmotactic index), whereas at a higher dose (500
      microg/kg, IP) produced general inhibitory influence, and decreased the anti
      thigmotactic index. Analysis of the behavioral and biochemical results of the
      experiment revealed a significant negative correlation between the ligand binding
      in the substantia nigra pars reticulata (SNR), and the number of entries into the
      central sector of the open field (r=-0.48, p<0.05), as well as the positive
      correlation between time spent in the central sector of the open field and [3H]
      raclopride binding within nucleus accumbens septi (r=0.57, p<0.05). Factor
      analysis revealed a Factor 1 (eigenvalue=3.361) grouping parameters of central
      entries into the open field and [3H]-raclopride binding in the SNR (factor
      loadings are 0.814 and 0.703 respectively), indicating that both phenomena are
      under control of a similar central process. The above data are discussed in
      relation to the structure dependent dopamine D2 receptor mechanisms in a rat
      response to novelty.

PMID- 15581908
TI  - Endurance treadmill training in rats alters CRH activity in the hypothalamic
      paraventricular nucleus at rest and during acute running according to its period.
AB  - Running training on the treadmill increases the resting hypothalamic
      corticotropin-releasing hormone (CRH) content in rats, though is still unknown
      whether and how it occurs in the parvocellular region of the hypothalamic
      paraventricular nucleus (PVN) where is a predominant region of pituitary-adrenal
      activity and where CRH and arginine vasopressin (AVP) are colocalized. We thus
      aimed at examining whether treadmill training would alter the CRH and AVP mRNA
      levels in the PVN at rest and during acute running with different lengths of a
      training regime. Male Wistar rats were subjected to treadmill running
      (approximately 25 m/min, 60 minutes/day, 5 times/week) for training regimes of 0,
      1, 2 or 4 weeks. All training regimes induced an adrenal hypertrophy. Plasma
      corticosterone levels before acute running increased with lengthening the
      training period. Four weeks of training produced a significant increase in the
      resting CRH, but not AVP, mRNA levels in the PVN though relatively shorter
      training regimes did not. Acute responses of lactate and ACTH release were
      reduced after 2 and 4 weeks of training, respectively. The responsive PVN CRH
      mRNA level to acute running decreased with 4 weeks of training but increased with
      relatively shorter training regimes. These results indicate that running training
      changes the PVN CRH biosynthetic activity with the regime lasting for 4 weeks,
      which follows adaptive changes in adrenal functions. Thus, running training
      induced changes in hypothalamic CRH activity would originate from the PVN and be
      induced according to the training period.

PMID- 15581909
TI  - Artichoke juice improves endothelial function in hyperlipemia.
AB  - Artichoke extracts have been shown to produce various pharmacological effects,
      such as the inhibition of cholesterol biosynthesis and of LDL oxidation.
      Endothelial dysfunction represents the first stage of atherosclerotic disease; it
      is usually evaluated in humans by a noninvasive ultrasound method as brachial
      flow-mediated vasodilation (FMV) and by the determination of several humoral
      markers such as vascular cell adhesion molecule-1 (VCAM-1), intercellular
      adhesion molecule-1 (ICAM-1), and E-selectin. Aim of the study was to investigate
      the effects of dietary supplementation with artichoke juice on brachial FMV of
      hyperlipemics. We studied 18 moderately hyperlipemic patients (LDL cholesterol >
      130 <200 mg/dl and/or triglycerides >150 <250 mg/dl) of both genders and 10
      hyperlipemic patients, matched for age, sex and lipid parameters. All subjects
      were under isocaloric hypolipidic diet. A basal determination of serum lipids,
      soluble VCAM-1, ICAM-1, E-selectin and brachial FMV was performed. Thereafter
      patients were given 20 ml/die of frozen artichoke juice. The same parameters were
      repeated after 6 weeks. After artichoke treatment there was an increase of
      triglycerides (156 +/- 54 vs 165 +/- 76 mg/dL, p <0.05) and a reduction of total
      cholesterol (261 +/- 37 vs 244 +/- 38 mg/dL, p <0.05) and LDL cholesterol (174 +/
      31 vs 160 +/- 34 mg/dL, p <0.05). Controls showed a significant decrease in
      total and LDL cholesterol (respectively: 267 +/- 22 vs 249 +/- 20 mg/dL and 180
      +/- 24 vs 164 +/- 23 mg/dL, both p <0.001). After artichoke there was a decrease
      in VCAM-1(1633 +/- 1293 vs 1139 +/- 883 ng/mL, p <0.05) and ICAM-1(477 +/- 123 vs
      397 +/- 102 ng/mL, p <0.05), brachial FMV increased (3.3 +/- 2.7 vs 4.5 +/- 2.4%,
      p <0.01), while controls did not exhibit significant changes in VCAM-1, ICAM-1, E
      selectin and brachial FMV. Univariate analysis showed that, in artichoke
      patients, changes of VCAM-1 and ICAM-1 were significantly related to changes in
      brachial FMV (respectively: r=-0.66 and r=-0.62; both p <0.05). In conclusion,
      artichoke dietary supplementation seems to positively modulate endothelial
      function in hypercholesterolemia.

PMID- 15581910
TI  - Scratching of their skin by NC/Nga mice leads to development of dermatitis.
AB  - Effects of scratching behavior on dermatitis, transepidermal water loss (TEWL)
      and serum IgE concentrations were examined in NC/Nga (NC) mice with toenails
      (WIT) and without toenails (WOT). The first study was a preventive treatment done
      to cut off hind toenails before dermatitis induction and the second study was a
      therapeutic treatment by cutting off hind toenails of NC mice with severe
      dermatitis. In the preventive study, scratching behavior significantly increased
      in both WIT and WOT after dermatitis induction. Skin severity score, TEWL, number
      of mast cells and serum IgE concentration statistically increased in WIT but not
      in WOT after dermatitis induction. Histological changes coincided with the skin
      severity score in WIT, while no changes were observed in WOT. In the therapeutic
      study, skin severity score in WOT but not in WIT statistically decreased after
      cutting off the hind toenails. TEWL and numbers of mast cells in WOT were
      statistically lower compared with findings in WIT. Thus scratching up the skin
      with toenails seemed to be the most important factor leading to dermatitis in NC
      mice.

PMID- 15581911
TI  - Effects of thymulin and GnRH on the release of gonadotropins by in vitro
      pituitary cells obtained from rats in each day of estrous cycle.
AB  - The effects of thymulin and GnRH on FSH and LH release were studied in suspension
      cultures of anterior pituitary cells from female adult rats sacrificed on each
      day of the estrous cycle. The spontaneous release of gonadotropins by
      pituitaries, as well as their response to GnRH or thymulin addition, fluctuated
      during the estrous cycle. Adding thymulin to pituitary cells from rats in
      diestrus 1 increased the concentration of FSH; while in cells from rats in
      estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal
      concentration of LH during most days of the estrous cycle. Adding GnRH increased
      FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and
      resulted in higher LH levels in cells obtained from rats in all days of the
      estrous cycle. Compared to the GnRH treatment, the simultaneous addition of
      thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus
      resulted in lower FSH concentrations. Similar results were observed in the LH
      release by cells from rats in diestrus 1, while in cells from rats in proestrus
      or estrus, LH concentrations increased. A directly proportional relation between
      progesterone serum levels and the effects of thymulin on FSH release was
      observed. These data suggest that thymulin plays a dual role in the release of
      gonadotropins, and that its effects depend on the hormonal status of the donor's
      pituitary.

PMID- 15581912
TI  - Increased cerebrospinal fluid levels of S100B protein in rat model of mania
      induced by ouabain.
AB  - Bipolar disorder is a chronic and severe mental disorder. Recently, new animal
      models have emerged to further investigate underlying mechanisms of bipolar
      disorder such as ouabain-induced hyperactivity in rats. In this study, we
      investigated the cerebrospinal fluid levels of S100B protein as a putative marker
      of astrocytic activity in bipolar mania induced by intracerebroventricular
      administration of ouabain in rats. Ouabain induced a two-fold increase in
      crossing responses in the open field test and increased 30% the cerebrospinal
      fluid concentration of S100B, as compared to vehicle group. Our findings
      reinforce the role of astroglial cells in the pathogenesis of bipolar disorder
      and S100B protein as a marker of bipolar mania.

PMID- 15581913
TI  - Saikosaponin C induces endothelial cells growth, migration and capillary tube
      formation.
AB  - Saikosaponin C is one of the saikosaponins that are consisted in a Chinese herb,
      Radix Bupleuri. Recently, saikosaponins have been reported to have properties of
      cell growth inhibition, inducing cancer cells differentiation and apoptosis.
      However, saikosaponin C had no correlation with cell growth inhibition. In this
      study, we investigated the role of saikosaponin C on the growth of endothelial
      cells and angiogenesis. We found that saikosaponin C yielded a potent effect on
      inducing human umbilical vein endothelial cells (HUVECs) viability and growth. In
      addition to inducing endothelial cells growth, saikosaponin C also induced
      endothelial cells migration and capillary tube formation. The gene expression or
      activation of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth
      factor (VEGF) and the p42/p44 mitogen-activated protein kinase (MAPK, ERK) that
      correlated with endothelial cells growth, migration and angiogenesis were also
      induced by saikosaponin C. From these results, we suggest that saikosaponin C may
      have the potential for therapeutic angiogenesis but is not suitable for cancer
      therapy.

PMID- 15581914
TI  - Arimidex inhibition on proliferation of human breast solid tumors measured by ATP
      bioluminescence.
AB  - To determine the degree of Arimidex (Anastrozole) inhibition on proliferation of
      human breast solid tumors in vitro by ATP bioluminescence assay. Breast cancer
      solid tumors with different hormone receptors and grading were collected from 38
      Chinese women with invasive breast cancers. Tumors were treated with three
      concentrations of Arimidex (1.5 mM, 15 mM and 150 mM). ATP bioluminescence assay
      was used to measure the metabolic rate in order to determine the degree of
      inhibition of Arimidex on the breast cancer tumors by comparing to the untreated
      tumors. 15 mM Arimidex shows greatest inhibitory effect on the proliferation of
      solid tumors with ER-postive/PR-positive. It can also inhibit the growth of
      metastatic tumors and tumors with HER-2/neu expression. It shows greater
      inhibitory effect in lower grading of tumors then higher. Arimidex may
      effectively inhibit the growth of breast tumors in in vitro system by inhibiting
      aromatase and block estrogen dependent tumor growth.

PMID- 15581915
TI  - Effects of the intravitreal administration of dopaminergic ligands on the b-wave
      amplitude of the rabbit electroretinogram.
AB  - In the retina of mammals, dopamine (DA) is generally released by amacrine cells
      and is known to alter the physiology of most retinal cells. It is well known that
      DA reduces the amplitude of the b-wave of the electroretinogram (ERG) in rabbit.
      However, the specific receptor subtypes that mediate this action have not yet
      been elucidated. To do this, we recorded flash ERGs before and after the
      intravitreal injection of D1-like DA receptor agonists (SKF38393, A77693) and
      antagonist (SCH23390), and of D2-like agonist (R(-)-propylnorapomorphine
      hydrochloride; NPA) and antagonist ((S)-(-)-sulpiride). Contralateral control
      eyes were injected with the vehicle only. Both D1 agonists provoked a reduction
      of the ERG b-wave amplitude (34.0% and 59.2% of the pre-injection level,
      respectively). The D2-like agonist NPA had no significant effects on ERG
      components. Unexpectedly, both D1- and D2-like antagonists also reduced the b
      wave amplitude (28.9% and 59.8%). Overall, these data suggest that the previously
      described effect of DA on the rabbit ERG b-wave came from activation of D1-like
      receptors. On the basis of the effects observed with D2-like antagonist, a subtle
      contribution of D2-like presynaptic receptors cannot be ruled out.

PMID- 15581916
TI  - Two realms of dark adaptation.
AB  - The recovery of rod responsiveness after saturating flashes is greatly retarded
      above a certain critical level of rhodopsin bleaching (approximately 0.1%). A
      mathematical description of the process of turn-off of the phototransduction
      cascade allows attributing different phases of the recovery to specific products
      of rhodopsin photolysis. The fast phase is determined by quenching of
      metarhodopsin II and activated transducin. The slow phase is controlled by decay
      of partially inactivated (phosphorylated and arrestin-bound) metarhodopsins, and
      by regeneration of rhodopsin. The transition between the two regimes of
      adaptation is rather abrupt, occurring within a few-fold range of stimulus
      intensity. This marks the border between reversal of light adaptation and dark
      adaptation, as it is commonly defined.

PMID- 15581917
TI  - Parafoveal-on-foveal effects in normal reading.
AB  - A corpus of eye movement data derived from 10 English and 10 French participants,
      each reading about 50,000 words, was examined for evidence that properties of a
      word in parafoveal vision have an immediate effect on foveal inspection time.
      When inspecting a short word, there is evidence that the lexical frequency of an
      adjacent word affects processing time. When inspecting a long word, there are
      small effects of lexical frequency, but larger effects of initial-letter
      constraint and orthographic familiarity. Interactions of this kind are
      incompatible with models of reading which appeal to the operation of a serial
      attention switch.

PMID- 15581918
TI  - Effects of elevated intraocular pressure on mouse retinal ganglion cells.
AB  - We developed and characterized a mouse model of elevated intraocular pressure
      (IOP) to investigate the underlying cellular and genetic mechanisms of retinal
      ganglion cell (RGC) death. IOP was unilaterally increased in C57BL/6J mice by
      photocoagulation of the episcleral and limbal veins. IOP was measured using an
      indentation tonometer. RGC survival was measured by retrograde labeling using DiI
      applied to the superior colliculous. The mechanism of RGC death was investigated
      using TUNEL staining, immunostaining for cleaved caspase-3, and Western blot for
      Bcl-2 and Bax expression. RT-PCR was used to measure changes in Bcl-2, Bax, Bad,
      Bak, P53, ICE and Fas. Mean IOP was increased in the treated eyes from 13+/-1.8
      to 20.0+/-2.8 mmHg at four weeks and 17+/-2.2 mmHg at eight weeks. RGC loss was
      15.6+/-3.4% at two weeks and 27.3+/-4.5% at four weeks after laser
      photocoagulation. TUNEL staining and caspase-3 positive cells were increased in
      the ganglion cell layer (GCL) in the treated eyes and seldom found in the control
      eyes. Bcl-2 expression in control group was higher than in the experimental
      group, while Bax expression in the control group was less than in experimental
      group. This mouse model resulted in a consistent, sustained increase in IOP with
      a reduction in the number of RGCs in the treated eye. The RGCs in eyes with
      elevated IOP were TUNEL-positive, with increased caspase-3 and decreased Bcl-2,
      consistent with apoptosis as the mechanism of neuronal cell death.

PMID- 15581919
TI  - Dynamics of accommodative fatigue in rhesus monkeys and humans.
AB  - Changes in accommodative dynamics with repeated accommodation were studied in
      three anesthetized rhesus monkeys and two conscious humans. Maximum accommodation
      was centrally stimulated via the Edinger-Westphal nucleus in monkeys with a 4 s
      on, 4 s off paradigm (4 x 4) for 17 min, 4 x 1.5 for 27 min and 2 x 1 for 16 min.
      Humans accommodated repeatedly to visual targets (5 x 5; 5D and 2 x 2; 6D) for 30
      min. In all cases, accommodation was sustained throughout. The anesthetized
      monkeys showed inter-individual variability in the extent of changes in
      accommodative dynamics over time while no systematic changes were detected in the
      human accommodative responses. Little accommodative fatigue was found compared to
      previous studies which have reported a complete loss of accommodation after 5 min
      of repeated stimulation in monkeys.

PMID- 15581920
TI  - A psychoanatomical investigation of the blanking phenomenon.
AB  - One cannot detect a white disk located at least 15 degrees from fixation in an
      intersection of gray alleys that define a grid of black squares. A psychophysical
      examination of the anatomical locus of this "blanking phenomenon" is reported
      here. Stimuli were presented dichoptically; disk threshold was measured with
      fixed-step staircases. Three dichoptic experiments were developed employing
      different stimuli. Simple dichoptic presentations implied both pre- and post
      fusion contributions. One follow-up experiment verified pre-fusion contributions,
      while another implicated post-fusion mechanisms. These results indicate that the
      blanking phenomenon has contributions from multiple sites in the visual system.

PMID- 15581921
TI  - Modeling the influence of task on attention.
AB  - We propose a computational model for the task-specific guidance of visual
      attention in real-world scenes. Our model emphasizes four aspects that are
      important in biological vision: determining task-relevance of an entity, biasing
      attention for the low-level visual features of desired targets, recognizing these
      targets using the same low-level features, and incrementally building a visual
      map of task-relevance at every scene location. Given a task definition in the
      form of keywords, the model first determines and stores the task-relevant
      entities in working memory, using prior knowledge stored in long-term memory. It
      attempts to detect the most relevant entity by biasing its visual attention
      system with the entity's learned low-level features. It attends to the most
      salient location in the scene, and attempts to recognize the attended object
      through hierarchical matching against object representations stored in long-term
      memory. It updates its working memory with the task-relevance of the recognized
      entity and updates a topographic task-relevance map with the location and
      relevance of the recognized entity. The model is tested on three types of tasks:
      single-target detection in 343 natural and synthetic images, where biasing for
      the target accelerates target detection over twofold on average; sequential
      multiple-target detection in 28 natural images, where biasing, recognition,
      working memory and long term memory contribute to rapidly finding all targets;
      and learning a map of likely locations of cars from a video clip filmed while
      driving on a highway. The model's performance on search for single features and
      feature conjunctions is consistent with existing psychophysical data. These
      results of our biologically-motivated architecture suggest that the model may
      provide a reasonable approximation to many brain processes involved in complex
      task-driven visual behaviors.

PMID- 15581922
TI  - Accommodative state of young adults using reading spectacles.
AB  - We examined the accommodative state of young adults wearing +2D and +3D reading
      spectacles under normal conditions and with the elimination of accommodative
      cues. Subjects' refractions were measured with an infrared PowerRefractor. Power
      of the vertical meridian was recorded for subjects viewing far and near targets
      in free space and through a Badal lens apparatus with and without reading
      spectacles. Additionally, refractive measurements were taken after subjects wore
      +2D reading spectacles for 30 min (post-adaptation). In free viewing and viewing
      through the Badal lens, subjects uniformly over-accommodated relative to the
      target while wearing reading spectacles (i.e., with the spectacles, they focused
      at a plane in front of the target). Subjects in the first post-adaptation test
      showed no significant difference in accommodation between viewing a near target
      with and without +2D spectacles after having read with them for 30 min, though
      they had without post-adaptation. Subjects in the second post-adaptation test
      were not significantly differently accommodated before and after reading when
      binocularly viewing a near target with +2D reading spectacles. The results imply
      that no adaptation of the subjects' accommodative postures while viewing visual
      targets occurred as a result of a 1/2 h near work task with the spectacles. The
      over-accommodation of subjects using reading spectacles while they are performing
      visual tasks shows the necessity of measurement if their true accommodative
      posture is to be determined.

PMID- 15581923
TI  - Visual grouping on binocular rivalry in a split-brain observer.
AB  - We studied the effects of visual grouping on binocular rivalry in the left and
      right hemispheres of a split-brain observer, JW. In Experiments 1 and 2, we
      compared responses to traditional rivalry stimuli (e.g., a red vertical grating
      presented to the left eye and a green horizontal grating presented to the right
      eye) with responses to Diaz-Caneja stimuli (i.e., half of each grating was
      presented to one eye and the other half to the other eye). As found for intact
      brain observers, JW reported episodes of exclusive visibility of coherent stimuli
      (e.g., of a red vertical grating alternating with a green horizontal grating)
      with Diaz-Caneja stimuli that were fewer and briefer than with traditional
      stimuli. This occurred in both hemispheres, demonstrating that during binocular
      rivalry, contours from one eye can be grouped with those of the opposite eye to
      create a coherent percept, even in the isolated hemispheres of the split-brain
      observer. In Experiment 3, we studied the tendency of rivalry in adjacent patches
      to synchronize. When both patches were in one of JW's hemifields, rivalry
      synchronized for similarly oriented stimuli, the same as happened for intact
      brain observers. When the patches were in JW's opposite hemifields, there was no
      synchronizing of rivalry, unlike what happened for intact-brain observers. This
      suggests that rivalry processed in JW's two hemispheres is independent. We
      conclude that rivalry is processed fully within each hemisphere.

PMID- 15581924
TI  - Temporal properties of retinal ganglion cell responses to local transretinal
      current stimuli in the frog retina.
AB  - Extracellular current stimuli have been used in both electrophysiological and
      clinical studies. The present study elucidates the temporal properties of the
      frog retinal ganglion cell response induced by local transretinal current
      stimuli. Two classes of spike response were recorded from the ganglion cell. One
      had a constant latency ranging from 1.5 to 4.5 ms after the onset of the stimulus
      regardless of differences in stimulus parameters. Another class had a latency
      that varied from trial to trial between 3.5 and 71.5 ms at the threshold even
      when stimulus parameters were identical. The latency became shorter and the
      number of spike responses increased as the charge applied via the stimulus pulse
      was increased by increasing the amplitude (from 50 to 200 microA) or the pulse
      duration (from 100 to 1000 micros). In both classes, the current stimuli with the
      same amount of charge induced responses of a similar latency for amplitudes
      between 50 and 200 microA and for pulse durations between 100 and 1000 micros.

PMID- 15581925
TI  - Correlation of PCDD/F and PCB concentrations in soil samples from the Swiss soil
      monitoring network (NABO) to specific parameters of the observation sites.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F)
      and polychlorinated biphenyls (PCB) were determined in 23 soil samples collected
      at reference sites of the Swiss national soil monitoring network (NABO). Total
      PCDD/F and PCB concentrations are well correlated and proportional (R2=0.720).
      The total PCDD/F levels were between 72 and 703 ng/kg corresponding to 1.1-11 ng
      I-TEQ/kg, total PCB concentrations (sum of seven congeners IUPAC no. 28, 52, 101,
      118, 138, 153, and 180) were from 1.1 to 12 microg/kg. In all samples, the PCDD/F
      and PCB concentrations were in the range of background levels for these
      contaminants in Central Europe. Ninteen samples revealed PCDD/F levels below the
      guide value of 5 ng I-TEQ/kg set by the Swiss ordinance relating to impacts on
      the soil (OIS); concentrations for the remaining four samples were below the
      trigger value (20 ng I-TEQ/kg). All PCB concentrations were below the guide value
      of 100 microg/kg. The elevated PCDD/F and PCB levels in some of the samples
      originating from forested sites could be attributed to the scavenging effect of
      forest canopies for semivolatile organic compounds. This interpretation could be
      substantiated by the observed distortion of the congener and homolog patterns of
      PCDD/F and PCB which is characteristic for forested sites.

PMID- 15581926
TI  - Congener-specific concentrations and carbon stable isotope ratios (delta13C) of
      two technical toxaphene products (Toxaphene and Melipax).
AB  - In this study we compared the contribution of individual congeners and the ratios
      of stable carbon isotopes of two technical toxaphene products. The former US
      American product Toxaphene was from 1978 and the East-German product Melipax from
      1979. Both technical products showed the known complexity in GC/ECD measurements.
      Contributions of 24 peaks to each of the technical products were determined by
      gas chromatography in combination high resolution electron capture negative ion
      mass spectrometry (GC/ECNI-HRMS). The percentages of the compounds studied in the
      technical mixtures ranged from approximately 0.05% to approximately 2.5% but
      showed some individual differences. 2,2,5,5,8,9,9,10,10-nonachlorobornane (B9
      1025 or P-62) was identified as a major congener in both mixtures. 2-Endo,3-exo,5
      endo,6-exo,8,8,10,10-octachlorobornane (B8-1413 or P26) and 2-endo,3-exo,5-endo,6
      exo,8,8,9,10,10-nonachlorobornane (B9-1679 or P-50) were found at similar
      concentration in both technical products. Identical amounts of Melipax or
      Toxaphene were combusted to CO2 in an element analyzer and their delta13C values
      were determined relative to the international standard Vienna PeeDee belemnite
      (VPDB). The mean delta13C values of both products varied by 2.8% (determined at
      two different locations) which is roughly one order of magnitude more than the
      precision obtained in repetitive analyses of the individual products. Thus, both
      investigated products could be unequivocally distinguished by stable isotope
      ratio mass spectrometry (IRMS). IRMS analyses may thus be a suitable tool for
      tracing back toxaphene residues in environmental and food samples to the one or
      both of the products.

PMID- 15581927
TI  - Kinetics of OH radical reactions with dibenzo-p-dioxin and selected chlorinated
      dibenzo-p-dioxins.
AB  - The pulsed laser photolysis/pulsed laser-induced fluorescence (PLP/PLIF)
      technique has been applied to obtain rate coefficients for OH + dioxin (DD) (k1),
      OH + 2-chlorodibenzo-p-dioxin (2-CDD) (k2), OH + 2,3-dichlorodibenzo-p-dioxin
      (2,3-DCDD) (k3), OH + 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD) (k4), OH + 2,8
      dichlorodibenzo-p-dioxin (2,8-DCDD) (k5), OH + 1,2,3,4-tetrachlorodibenzo-p
      dioxin (1,2,3,4-TCDD) (k6), and OH + octachlorodibenzo-p-dioxin (OCDD) (k7) over
      an extended range of temperature. The atmospheric pressure (740 +/- 10 Torr) rate
      measurements are characterized by the following Arrhenius parameters (in units of
      cm3 molecule(-1) s(-1), error limits are 1 omega): k1(326-907 K) = (1.70+/-0.22)
      x 10(-12)exp(979+/-55)/T, k2(346-905 K) = (2.79+/-0.27) x 10(-12)exp(784+/-54)/T,
      k3(400-927 K) = 10(-12)exp(742+/-67)/T, k4(390-769 K) = (1.10+/-0.10) x 10(
      12)exp(569+/-53)/T, k5(379-931 K) = (1.02+/-0.10) x 10(-12)exp(580+/-68)/T,
      k6(409-936 K) = (1.66+/-0.38) x 10(-12)exp(713+/-114)/T, k7(514-928 K) = (3.18+/
      0.54) x 10(-12)exp(-667+/-115)/T. The overall uncertainty in the measurements,
      taking into account systematic errors dominated by uncertainty in the substrate
      reactor concentration, range from a factor of 2 for DD, 2-CDD, 2,3-DCDD, 2,7
      DCDD, and 2,8-DCDD to +/- a factor of 4 for 1,2,3,4-TCDD and OCDD. Negative
      activation energies characteristic of an OH addition mechanism were observed for
      k1-k6. k7 exhibited a positive activation energy. Cl substitution was found to
      reduce OH reactivity, as observed in prior studies at lower temperatures. At
      elevated temperatures (500 K < T < 500 K), there was no experimental evidence for
      a change in reaction mechanism from OH addition to H abstraction. Theoretical
      calculations suggest that H abstraction will dominate OH reactivity for most if
      not all dioxins (excluding OCDD) at combustion temperatures (>1000 K). For OCDD,
      the dominant reaction mechanism at all temperatures is OH addition followed by Cl
      elimination.

PMID- 15581928
TI  - Analysis of short chain chlorinated paraffins in sediment samples from the Czech
      Republic by short-column GC/ECNI-MS.
AB  - Top layer sediment samples from the Czech Republic were analyzed to obtain the
      preliminary information about contamination of the region by chlorinated
      paraffins. Sediment samples from three locations with different industrial
      discharges were taken over the period of 2 years. The analysis was performed by
      short-column gas chromatography-electron capture negative ion mass spectrometry
      (SCGC/ECNI-MS). Short chain chlorinated paraffin sediment concentrations varied
      between 24.00 and 45.78 ng g(-1) (dry weight, d.w.) in the Kosetice area, 16.30
      180.75 ng g(-1) (dry weight) in the Zlin area and 4.58-21.57 ng g(-1) dry weight
      in the Beroun area. Highly chlorinated undecanes prevailed in the samples. On the
      basis of these results, more detailed studies should be conducted to determine
      the magnitude and extent of chlorinated paraffin contamination in these regions.

PMID- 15581929
TI  - Enhanced bioavailability of sorbed 2,4,6-trinitrotoluene (TNT) by a bacterial
      consortium.
AB  - Large quantities of trinitrotoluene (TNT) have been associated with past and
      present military activities worldwide. Because this contaminant is highly toxic
      and strongly sorbs to soil particles, bacteria that are able to transform it have
      had very little success, if any. This study was conducted to evaluate the
      bioavailability of 14C-labeled TNT in soil for microbial mineralization. Sorption
      desorption experiments indicated that a Kendaia loam soil effectively adsorbs
      this explosive compound, with approximately 30-45% of the added TNT remaining
      sorbed to the soil after a total of 10 washings. A bacterial consortium isolated
      from explosive-contaminated sites was prepared in liquid medium and then tested
      in a TNT-spiked Kendaia loam soil. The concentration of TNT in the soil that was
      inoculated with the bacterial consortium was reduced by more than 30% of the
      initial concentration compared to the soil that did not contain the bacterial
      consortium within a period of 20 weeks. Nearly half of the TNT was mineralized as
      determined by the percentage of 14CO2 produced. Only one member of the consortium
      (i.e., Enterobacter sp.) significantly mineralized 25% of TNT although the extent
      of mineralization was significantly enhanced to 35% in the presence of the other
      two members of the consortium. The data suggest that some of the strongly
      adsorbed TNT may be accessible for metabolism if conditions for the right
      combination of microorganisms with specialized capabilities are optimized. The
      remaining sorbed fraction of substrate is presumably sequestered and thus
      unavailable to the microorganisms.

PMID- 15581930
TI  - Organochlorine pollutants in soils and mosses from Victoria Land (Antarctica).
AB  - The major organochlorine (OC) pollutants, i.e. pentachlorobenzene (PCBz),
      hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), polychlorobiphenyls
      (PCBs) and DDTs have been analyzed in soils and mosses from coastal areas of
      Victoria Land (70-80 degrees S, 160-170 degrees E). PCBs (23-34 ng g(-1) dry wt.)
      and PCBz (0.38-1.3 ng g(-1) dry wt.) were the dominant OCs in mosses and soils,
      respectively. In general, the concentrations of OC in soils, i.e. HCB (0.034-0.17
      ng g(-1) dry wt.), PCBs (0.36-0.59 ng g(-1) dry wt.) and 4,4'-DDE (0.053-0.086 ng
      g(-1) dry wt.), range among the lowest reported in remote regions. These
      concentrations exhibited high correlation coefficients when represented vs. total
      organic carbon (TOC) which is consistent with the general correlation between OC
      and TOC in soils from remote areas recently observed (Meijer, S.N., Ockenden,
      W.A., Seetman, A., Breivik, K., Grimalt, J.O., Jones, K.C., 2003. Global
      distribution and budget of PCBs and HCB in background surface soils: implications
      for sources and environmental processes. Environ. Sci. Technol. 37, 667-672).
      Statistically significant dependences between reciprocal of temperature and log
      transformed concentrations of HCB and 4,4'-DDE in mosses and alpha-HCH in soils
      have been found. These observations provide further data illustrating that
      temperature is a major factor determining the planetary scale distribution and
      accumulation of OCs giving additional ground to the general validity of the
      global distillation effect for description of planetary OC distribution.

PMID- 15581931
TI  - The changing state of contamination in the Lagoon of Venice. Part 1: organic
      pollutants.
AB  - The Lagoon of Venice is a transitional environment suffering from industrial,
      urban and agricultural impact. Recently the mechanical clam fishing, preventing a
      regular deposition of sediments has made sampling of cores suitable for
      radiodating very problematic. Therefore, in this study, in order to assess
      temporal and spatial trends of contamination, the same sampling scheme was
      repeated three times over a 12-year period. The concentrations of PCBs, PAHs and
      organochlorine pesticides were measured in the uppermost 5 cm of sediments
      collected in 25 sites in the central portion of the lagoon during three campaigns
      conducted in 1987, 1993 and 1998. Analytical results, validated statistically,
      indicated that, while PCB and pesticide concentrations tend to decrease during
      the considered period of time, PAH do not, showing that the input rate of these
      compounds to the lagoon environment is still important. A spatial trend of
      pollution was also found in the lagoon for PCBs and pesticides, which decrease
      from the sources, namely the industrial zone and the mouths of rivers, to areas
      closer to the sea: a reduction up to 80% and 90%, respectively, was monitored.
      PAH contamination, originating chiefly from incomplete combustion of fossil
      fuels, as inferred from ratios of congeners, was mainly located around the
      historical center of Venice, where most of the boat traffic is concentrated and
      has an increasing trend.

PMID- 15581932
TI  - Dissolution and removal of PAHs from a contaminated soil using sunflower oil.
AB  - This study reports on the feasibility of remediation of polycyclic aromatic
      hydrocarbon (PAH) contaminated soils using sunflower oil, an environmentally
      friendly solvent. Batch experiments were performed to test the influence of
      oil/soil ratio on the remediation of PAH contaminated soil, and to test the mass
      transfer behaviors of PAHs from soil to oil. An empirical model was employed to
      describe the kinetics of PAH dissolution and to predict equilibrium
      concentrations of PAHs in oil. PAH containing oil was regenerated using active
      carbon. Results show that dissolution of PAHs from a Manufactured Gas Plant (MGP)
      soil at oil/soil ratios of one or two were almost the same. Nearly all PAHs (81
      100%) could be removed by sunflower oil dissolution. Mass transfer coefficients
      for low molecular PAHs namely fluoranthene, phenanthrene and anthracene were one
      or two orders of magnitude higher than those for high molecular PAHs with 4-6
      rings. Ninety milliliters of PAH containing oil could be regenerated by 10 g
      active carbon in a batch reactor. Such a remediation procedure indicates that
      sunflower oil is a promising agent for the removal of PAHs from MGP soils.
      However, further research is required before the method can be used for in situ
      remediation of contaminated sites.

PMID- 15581933
TI  - Carbon/electron source dependence of polychlorinated biphenyl dechlorination
      pathways for anaerobic granules.
AB  - The effect of acclimating anaerobic granules from commercial bioreactors with
      different carbon/electron sources on their ability to reductively dechlorinate a
      tri-(2,3,4-CB) and heptachlorobiphenyl (2,2',3,3',4,5,6-CB) was studied. The
      anaerobic granules were first grown in upflow anaerobic sludge blanket (UASB)
      reactors fed with two different mixtures of carbon/electron sources, i.e.,
      propionate/butyrate/methanol and formate/methanol. Differences in dechlorination
      patterns for 2,2',3,3',4,5,6-CB were observed in batch experiments inoculated
      with granules from these two sets of UASB reactors. Variation of the
      carbon/electron source, during the dechlorination process, had no effect on the
      dechlorination pathway, but the extents and rates of dechlorination were highest
      for ethanol and formate and lowest for pyruvate fed batches. Pre-acclimation of
      different anaerobic sludges to polychlorinated biphenyls (PCBs) shortened the lag
      period, but did not influence the PCB dechlorination pathway. This is the first
      time that similar acclimation conditions for several anaerobic microbial
      communities prior to inoculation were reported to yield similar substrate
      specificities for the reductive dechlorination of specific PCB congeners. This
      research demonstrates a successful strategy for the development of biocatalysts
      to serve as the inoculum of partially decontaminated sites in order to provide
      microorganisms with specificities complementary to those of naturally occurring
      dechlorinators.

PMID- 15581934
TI  - Sorbent-assisted liquid-liquid extraction (Chem-Elut) of polychlorinated
      biphenyls, dibenzo-p-dioxins and dibenzofurans in the lipid fraction of human
      blood plasma.
AB  - This work compares two lipid extraction methods for determining 24
      polychlorinated biphenyls (PCBs), seven dibenzo-p-dioxins (PCDDs) and ten
      dibenzofurans (PCDFs) in human blood plasma. The first method was based on
      conventional liquid-liquid partitioning with chloroform-methanol and the other
      made use of a sorbent (Chem-Elut) to facilitate the partitioning of lipids into a
      mixture of hexane and 2-propanol. A multi-layer-silica column including acid- and
      base-impregnated silica gel was used to reduce the amounts of lipid present in
      the samples before a basic alumina clean-up step and activated carbon
      fractionation of planar analytes (PCDD/Fs and non-ortho-PCBs) and non-planar
      analytes (including ortho-chlorinated PCBs). Gas chromatography coupled to high
      resolution mass spectrometry was used to identify and quantify the analytes in
      the two fractions. The wet weight based concentrations obtained by the two
      methods were in agreement but both methods suffer from large organic solvent
      consumption. The toxic equivalencies derived for PCBs and PCDD/Fs using the two
      methods were also in agreement. However, the chloroform-methanol method gave
      slightly higher lipid recoveries, although with greater variation, than the
      sorbent-assisted method. Nevertheless, despite giving lower lipid recoveries, the
      sorbent-assisted method has advantages in ease of use and applicability to whole
      blood samples. The formation of emulsions was avoided with the Chem-Elut method,
      which probably explains the lower variability in the lipid determinations.

PMID- 15581935
TI  - Influence of pre-treatment step on PAHs analyses in contaminated soils.
AB  - There is no specific standardization for the pre-treatment of a soil sample for
      PAHs analyses. The ISO/FDIS 14507 method for soil quality gives a guidance for
      sample pre-treatment before measurement of organic contaminants in soil. It
      refers to cryogenic crushing which is not so easy to carry out. So, analysts lead
      to develop in house methods which can be very different from a laboratory to
      another and can involve deviations in the pollution quantification. This study
      has explored different ways of drying, grinding and sieving in order to determine
      the influence of the soil sample handling on the measured pollutant
      concentration. It appears that the influence of pre-treatment depends on the soil
      nature and on the PAHs distribution. As a conclusion, it is advised "light"
      drying ways like air drying or drying at 40 degrees C in a drying oven instead of
      more "drastic" ways (freeze-drying, cryogenic crushing) which can induce some
      losses. Crushing and sieving are also recommended for more reproducible measures.

PMID- 15581936
TI  - Concentrations of dioxins and related compounds in the blood of Fukuoka
      residents.
AB  - Blood samples of 152 residents (male 75 and female 77) aged 20-60 years in
      Fukuoka, Japan, were analyzed for dioxin toxic compounds of polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho
      polychlorinated biphenyls (non-ortho PCBs) and mono-ortho polychlorinated
      biphenyls (mono-ortho PCBs) as well as 35 PCB congeners and 12 chlorinated
      pesticides by high-resolution gas chromatography/high-resolution mass
      spectrometry. Average concentrations of dioxin toxic equivalents (TEQ) from
      PCDDs, PCDFs, non-ortho PCBs, mono-ortho PCBs and their total in the blood of 152
      residents were 10.28, 5.56, 7.75, 4.57 and 28.15 ppt in lipid, respectively.
      These total TEQ levels were comparable to the blood TEQ levels of normal Japanese
      (n=735). Lipid basis total TEQ levels progressively increased in the males from
      17.1 ppt at age 20s to 47.5 ppt at age 50s and in the females from 19.5 ppt at
      age 20s to 54.5 ppt at age 50s. Dioxin toxic contribution of PCBs to total TEQ
      was increased from 31% at age 20s to 55% at age 50s. Average concentrations of
      total 35 PCBs and total 12 pesticides in the blood of 151 residents were 386 and
      1079 ppb in lipid, respectively. Average concentrations (ppb in lipid) of total
      PCBs and total pesticides also progressively increased in the males from 213 and
      444 at age 20s to 868 and 2140 at age 50s, respectively, and in the females from
      199 and 588 at age 20s to 550 and 1977 at age 50s, respectively. The levels of
      TEQ, PCBs, hexachlorobenzene, beta-hexachlorocyclohexane, dieldrin, p,p'
      dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyltrichloroethane, trans
      nonachlor and cis-nonachlor were positively correlated with each other in most of
      the combinations, and the highest correlations (r>0.8) were observed between
      total TEQ and PCBs in both sexes.

PMID- 15581937
TI  - Polybrominated diphenyl ethers and selected organochlorine chemicals in grey
      seals (Halichoerus grypus) in the North Sea.
AB  - Blubber samples from grey seal (Halichoerus grypus) pups were collected in 1998
      through to 2000. Twenty four newly weaned pups were sampled in November 1998, 13
      of which were re-sampled during their first year of life, between March and
      December 1999, and an additional 48 and 25 samples (new cohorts) were obtained in
      1999 (November-December) and 2000 (May-September) respectively. SimgaPBDE
      concentrations (sum of Di-HxBDEs) ranged from 45 to 1500 ng/g lipid, with a
      geometric mean of 290 ng/g lipid. BDE 47 dominated the congener profile, followed
      by BDEs 100, 99, 153 and 154. SimgaPCB concentrations (sum of 41 congeners)
      ranged from 100 to 93000 ng/g lipid, with a geometric mean of 4600 ng/g lipid,
      with CB congeners 153, 138 and 180 making up 84% of the total PCB concentrations.
      The predominant OC pesticides were p,p'-DDE (geometric mean=860 ng/g lipid,
      range=160-3800 ng/g lipid) and p,p'-DDT (geometric mean=120 ng/g lipid, range=30
      670 ng/g lipid). No significant differences were found between males and females,
      probably due to the young age of the animals. Significant decreases (P<0.01 for
      PBDEs and P<0.05 for PCBs/OCs) were observed between newly weaned seals in 1998
      and 1999, but not for the majority of juveniles in 1999 and 2000. Significant
      differences (P<0.01) were also found between the different seasons in 1999 newly
      weaned and juvenile seals, reflecting changes in blubber mass.

PMID- 15581938
TI  - Airborne PCB as a contamination risk on freeze-drying of sediment.
AB  - In a study of polychlorinated biphenyls (PCB) in freeze-dried sediments from
      Swedish lakes, the samples were found to contain unexpectedly high concentrations
      of PCBs. In one of the lakes (Bjorken), e.g. the concentration of PCB-28 was
      found to be 189 ng/g dw after freeze-drying compared to 7 ng/g dw after air
      drying of the sediment and therefore our hypothesis was that the contamination
      had occurred during the freeze-drying procedure. Hence, a dry reference sediment
      (RS) was used in order to identify potential sources of PCB contamination. The
      investigation included freeze-drying of the dry RS in five different
      laboratories, exposure to the air in the freeze-drying room, storage at room
      temperature and air-drying in a certain fume hood and in a laminar flow clean
      bench. The pattern and concentrations of PCBs detected in the exposed RS were
      strongly influenced by low chlorinated PCB congeners under all of these
      conditions with exception for air-drying in the fume hood. Storage in the
      laboratory air resulted in a slight elevation in the concentrations of low
      chlorinated PCB congeners, whereas higher concentrations of all PCB congeners
      were observed after freeze-drying. In all experiments the contamination appeared
      to be due to adsorption of PCB from the laboratory air. On the basis of these
      findings we recommend that reference material be subjected to the entire
      procedure, including sample preparation, in order to monitor contamination and
      that a procedure involving solvent extraction of wet sediment samples is used,
      whenever possible, instead of procedures involving dry samples.

PMID- 15581939
TI  - In-field measurements of PCDD/F emissions from domestic heating appliances for
      solid fuels.
AB  - Within this project the emissions into the atmosphere of polychlorinated dibenzo
      p-dioxins and -furans (PCDD/F) of 30 domestic heating appliances in Austrian
      households were tested. The appliances were single stoves (kitchen stove,
      continuous burning stove and tiled stove) and central heating boilers for solid
      fuels up to a nominal heat input of 50 kW. A main objective of this survey was to
      determine the PCDD/F emissions of domestic heating units under routine
      conditions. Therefore, the habitual combustion conditions used by the operators
      were not influenced. The original fuels and lightning supports were used and the
      operation of the units was carried out by the householders according to their
      usual practice. The data obtained were used to calculate in-field PCDD/F-emission
      factors. Most of the appliances have shown PCDD/F emissions within a
      concentration range of 0.01-0.3 ng TEQ/MJ. Modern fan-assisted wood heating
      boilers with afterburning and units for continuously burning of wood chips and
      wood pellets had the lowest emissions. High emissions were caused by unsuitable
      heating habits such as combustion of wastes and inappropriate operation of the
      appliances. There were only small differences between single stoves and central
      heating boilers or between wood and coal-fired appliances. The emission factors
      calculated are higher than those cited in literature, which are mainly derived
      from trials on test stands under laboratory conditions.

PMID- 15581940
TI  - Enhanced degradation of chlorinated ethylenes in groundwater from a paint
      contaminated site by two-stage fluidized-bed reactor.
AB  - Groundwater, used in this study, contaminated predominantly with aromatic
      compounds, was biologically treated in a fluidized-bed reactor (FBR) with
      immobilized cells. The aromatics were completely decomposed, while cis-1,2
      dichloroethylene (cis-DCE) and trichloroethylene (TCE) were decomposed only
      approximately 20% and 5%, respectively. In these studies a significant
      improvement of the decomposition efficiency for chlorinated ethylenes was
      achieved by utilizing cometabolism. Methanol (MeOH) and toluene were used as the
      substrate in the case of one-stage reactor (Single Reactor). MeOH (187 mg l(-1))
      increased the decomposition efficiency up to 40% and 60% for cis-DCE and TCE,
      respectively, while toluene (20 mg l(-1)) increased the decomposition efficiency
      of cis-DCE to 92% and the decomposition efficiency of TCE to 76%. In the case of
      two-stage reactor system (Reactor 1 and Reactor 2), MeOH and methane (CH4) were
      used as the substrate. In this system, cells grown on MeOH or CH4 in the Reactor
      1 were continuously fed into Reactor 2 and groundwater was fed into Reactor 2
      only. When MeOH (384 mg l(-1) d(-1)) was used as substrate the decomposition
      efficiency of cis-DCE and TCE were 60% and 70%, respectively. Similar
      decomposition efficiency was observed for a small amount of CH4 (19.3 mg l(-1) d(
      1)).

PMID- 15581941
TI  - The role of repeat uterine evacuation in the management of persistent gestational
      trophoblastic disease.

PMID- 15581942
TI  - The role of repeat uterine evacuation in the management of persistent gestational
      trophoblastic disease.
AB  - OBJECTIVE: To evaluate the role of second (and third) uterine evacuation in the
      management of persistent gestational trophoblastic disease (GTD). METHODS: This
      was an observational study of all cases registered over a 10-year period at the
      Trophoblastic Disease Centre at Weston Park Hospital, Sheffield. Five hundred and
      forty-four of 4050 women registered during 1991-2000 underwent a second uterine
      evacuation following a presumptive diagnosis of persistent GTD. The reason for
      evacuation, hCG level prior to the procedure, histological appearances of
      evacuated products and the clinical outcome (in terms of the need for
      chemotherapy) were determined. RESULTS: After a second uterine evacuation 368
      patients (68%) completed the follow-up programme without further evidence of
      persistent disease or need for chemotherapy. If the diagnosis of persistent GTD
      was confirmed solely on the basis of elevated hCG levels then 171 of 282 (60%)
      patients did not require chemotherapy. Chemotherapy was more likely where there
      was histological evidence of persistent trophoblastic disease and where the
      urinary hCG was >1500 IU/L at the time of the repeat evacuation. Twenty-eight of
      60 patients (46%) undergoing a third evacuation required chemotherapy.
      CONCLUSION: Second uterine evacuation can be a useful therapeutic option for
      patients with presumed persistent trophoblastic disease not mandating immediate
      chemotherapy, particularly where the hCG level is <1500 IU/L. Patients with
      documented persistent trophoblastic disease on histological examination of the
      second evacuation sample are more likely to require chemotherapy. Third
      evacuation is not now recommended.

PMID- 15581943
TI  - No differences in p53 mutation frequencies between BRCA1-associated and sporadic
      ovarian cancers.
AB  - OBJECTIVE: Mutation of the BRCA1 gene, which has incomplete penetrance, is
      involved in ovarian cancer development. Cell cycle check point inactivation via
      acquired somatic mutations in the check point regulatory genes, particularly p53,
      may be required for BRCA1-linked ovarian tumorigenesis. In the few studies
      directly comparing p53 mutations in BRCA1-linked and sporadic ovarian cancers,
      data have been contradictory. This study aimed to clarify the role of p53
      mutation in BRCA1-associated and sporadic ovarian cancer by comparing two, large,
      matched cohorts from two different populations who developed BRCA1-linked or
      sporadic ovarian cancers. METHODS: Forty-eight BRCA1-associated ovarian tumor
      samples (22 from Australia and 26 from Norway) were collected and matched with 48
      sporadic ovarian cancers for tumor stage, grade, histological subtype, and
      patient age. Expression of p53 protein was measured by immunohistochemistry
      (IHC). RESULTS: Consistent with the presence of a mutated p53 protein, the
      majority of BRCA1-associated (79%) and sporadic (73%) ovarian carcinomas from
      Australia and Norway overexpressed p53 protein. There was no significant
      difference between BRCA1-linked ovarian cancers and their sporadic counterparts
      with regard to p53 protein expression (P = 0.5). CONCLUSION: Our results suggest
      that p53 inactivation is associated with both BRCA1-associated and sporadic
      ovarian tumorigenesis, and that BRCA1-linked and sporadic ovarian cancers may
      develop through a similar carcinogenic pathway.

PMID- 15581944
TI  - Correlation of tumor- and stromal-derived MT1-MMP expression with progression of
      human ovarian tumors in SCID mice.
AB  - OBJECTIVE: Human ovarian carcinoma samples were orthotopically implanted into
      SCID mice to investigate the contribution of matrix metalloproteases (MMPs) to
      the spread of ovarian tumors. METHODS: Mice were inoculated with patient tumor
      samples, and developed ovarian tumors over a 16-week period with metastasis
      occurring in some mice. Species-specific quantitative RT-PCR was used to identify
      the source of tumor-associated MMPs. RESULTS: Membrane-type (MT)1-MMP mRNA was
      significantly increased in high-grade tumors, tumors with evidence of serosal
      involvement, and tumors in which distant metastases were detected. The increase
      in MT1-MMP expression was predominantly from the human tumor cells, with a minor
      contribution from the mouse ovarian stroma. Neither human nor mouse MT2-MMP were
      correlated with tumor progression and MT3-MMP levels were negligible. While tumor
      cells did not produce significant amounts of MMP-2 or MMP-9, the presence of
      tumor was associated with increased levels of MMP-2 expression by mouse ovarian
      stroma. Stromal-derived MT1-MMP was greater in large tumors and was associated
      with stromal MMP-2 expression but neither was significantly linked with
      metastasis. CONCLUSIONS: These studies indicate that tumor-derived MT1-MMP, more
      so than other gelatinolytic MMPs, is strongly linked to aggressive tumor
      behavior. This orthotopic model of human ovarian carcinoma is appropriate for
      studying ovarian tumor progression, and will be valuable in the further
      investigation of the metastatic process.

PMID- 15581945
TI  - Altered expression and loss of heterozygosity of the LOT1 gene in ovarian cancer.
AB  - OBJECTIVES: Previously, we demonstrated that the LOT1 (PLAGL1/ZAC1) gene encodes
      a zinc-finger transcription factor and has growth suppressive effects in
      carcinoma cell lines. The gene is localized on chromosome 6q24-25, a common site
      for loss of heterozygosity (LOH) in many solid tumors including ovarian cancer.
      In this study, we evaluated the LOT1 gene expression and allelic deletion in the
      tumor tissues in order to provide additional evidence to support the gene's
      potential role in cancer. METHODS: The LOT1 gene expression was analyzed in
      malignant ovarian epithelium obtained from frozen human ovarian tumor tissues
      using laser capture microdissection (LCM) and real-time PCR techniques. Highly
      frequent single nucleotide polymorphic (SNP) sites within the LOT1 gene were
      identified and used for PCR and direct sequencing to determine the occurrence of
      allelic imbalance in a series of surgically resected ovarian and breast
      carcinomas. RESULTS: The analysis revealed that LOT1 mRNA expression was not
      detectable in 12 of 31 (39%) cases of ovarian cancer and was variable between the
      remaining 19 tumor specimens. These findings are consistent with the previous
      data that showed altered expression of LOT1 in different human ovarian carcinoma
      cell lines. In addition, we analyzed the occurrence of LOT1 allelic deletion in
      different ovarian tumor genomic DNA samples that included papillary serous
      (majority), mucinous, and primary peritoneal adenocarcinomas of low- to high
      grade and the corresponding normal lymphocytes. The informative samples showed 12
      out of 33 or about 36.4% LOH of this gene based on allelic loss of one or more
      polymorphic sites within the LOT1 genomic sequences. Similarly, primary breast
      carcinomas, which included invasive ductal (majority), spindle cell, mucinous,
      giant cell, and atypical medullary carcinomas, were examined on genomic DNA from
      patients for the allelic loss of LOT1. The informative cases showed 4 out of 10
      samples or 40% LOH of this candidate tumor suppressor gene locus in breast
      cancer. CONCLUSIONS: The altered expression and LOH of the LOT1 locus support the
      gene's potential role, at least in part, in the pathogenesis of ovarian cancer
      and possibly in other types of cancer.

PMID- 15581946
TI  - The value of transvaginal ultrasonography in the prediction of endometrial
      pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated
      patients.
AB  - OBJECTIVE: There is no established ultrasonographic endometrial cutoff value for
      the diagnosis of endometrial pathologies in asymptomatic postmenopausal tamoxifen
      (TAM)-treated patients. We attempted to seek the most accurate cutoff value.
      MATERIALS AND METHODS: Multiple ultrasonographic cutoff points were evaluated by
      logistic regression analysis based on 279 patients who had transvaginal
      ultrasonographic examinations followed by endometrial histopathological analysis.
      Performance characteristics were calculated with correlation to the endometrial
      histological findings. We also calculated how many endometrial pathologies could
      have been left undiagnosed and the number of endometrial samplings, with
      different cutoff values, which could have been avoided. RESULTS: There was a
      gradual increase in specificity and a gradual decrease in sensitivity of the
      ultrasonographic studies with the increase of endometrial thickness. More overall
      and more various endometrial pathologies were identified with the increase in
      cutoff values. The best cutoff value appeared to be 15 mm (sensitivity 37.9%,
      specificity 87.2%, positive predictive value 63.0%, and negative predictive value
      70.2%). However, by avoiding performance endometrial sampling up to this cutoff
      value, 62.2% endometrial pathologies including 48 endometrial polyps, one case of
      endometrial hyperplasia with atypia, and one case of endometrial cancer may have
      been left undiagnosed. At the same time, endometrial sampling in 78.5% of cases
      may have been avoided. CONCLUSION: In asymptomatic postmenopausal breast cancer
      tamoxifen-treated patients, the use of wider ultrasonographic endometrial cutoff
      values could be associated not only with the performance of fewer endometrial
      samplings, but also with a higher possibility of endometrial pathologies,
      including endometrial cancers, being left undiagnosed.

PMID- 15581947
TI  - Predictors of final histology in patients with endometrial cancer.
AB  - OBJECTIVE: To assess the usefulness of preoperative tumor grade and
      intraoperative assessment of gross depth of myometrial invasion as "predictors"
      of final grade, final depth of myometrial invasion and surgical stage in patients
      with "low-risk" endometrial cancer. METHODS: We retrospectively compared
      preoperative histology and intraoperative gross depth of invasion with final
      pathologic evaluation on hysterectomy specimens. For patients traditionally
      considered intraoperatively to be "low-risk" for lymph node metastasis (grade 1
      or 2 adenocarcinoma with less than 50% myometrial invasion), "predictors"
      combining preoperative histology and intraoperative gross depth of myometrial
      invasion were established; that is, a preoperative biopsy of grade 1
      adenocarcinoma with an intraoperative gross depth of myometrial invasion of 30%
      was assigned the predictor IbG1 (Stage Ib, grade 1). These predictors were then
      compared to final grade and surgical stage. Sensitivity, specificity, and
      positive predictive value were then calculated. RESULTS: A total of 153 patients
      had both a preoperative biopsy and intraoperative assessment of gross depth of
      invasion. Twenty-four patients had the IaG1 predictor; eight had stage IaG1 on
      final pathologic evaluation (sensitivity, 0.50; specificity, 0.88; positive
      predictive value, 0.33). Eight patients had the IaG2 predictor; none had stage
      IaG2 on final pathologic evaluation (sensitivity, 0; specificity, 0.95; positive
      predictive value, 0). Eighty-nine patients had the IbG1 predictor; forty-six had
      stage IbG1 on final pathologic evaluation (sensitivity, 0.72; specificity, 0.52;
      positive predictive value, 0.52). Thirty-two patients had the IbG2 predictor; 11
      had stage IbG2 on final pathologic evaluation (sensitivity, 0.46; specificity,
      0.84; positive predictive value, 0.34). CONCLUSION: A clinically significant
      number of patients will have more advanced disease than predicted by preoperative
      or intraoperative prognostic factors. These predictors should not be relied on in
      the staging of endometrial cancer.

PMID- 15581948
TI  - Patients with uterine papillary serous cancers may benefit from adjuvant platinum
      based chemoradiation.
AB  - OBJECTIVE: The coexistence of minimal uterine disease and extrauterine metastases
      is common in patients with uterine papillary serous carcinoma (UPSC). Only
      complete surgical staging accurately depicts the extent of this disease. The
      purpose of this study was to evaluate different therapeutic options in surgically
      staged patients. METHODS: We retrospectively reviewed all patients with UPSC
      histologically limited in the uterus to the endometrium treated at our
      institution between 1987 and 2002. RESULTS: Twenty-three (45%) cases were
      International Federation of Gynecology and Obstetrics (FIGO) stage IA, seven
      (15%) were stage IIIA, one (2%) was stage IIIC, and nine (18%) stage IV.
      Additionally, 11 of these 51 patients (21%) were diagnosed with two cancers: a
      stage IA UPSC and concomitant advanced stage serous cancer of the ovary,
      fallopian tube, or peritoneum. Stage IA patients with no cancer in the
      hysterectomy specimen (defined as no residual uterine disease) had no recurrences
      (n = 10) regardless of treatment. There was a trend toward increased survival in
      stage IA patients with residual uterine disease who were treated with
      chemoradiation (concomitant vaginal brachytherapy and platinum-based
      chemotherapy). There were no recurrences in patients with locoregional disease
      (stages IA-IIIA) who received chemoradiation. All patients with advanced stage
      UPSC (stage IIIC or IV or two primary cancers) did poorly regardless of
      treatment. CONCLUSION: Our findings suggest that stage IA patients with no
      residual uterine disease may be observed. Stage IA patients with residual uterine
      disease may benefit from chemoradiation. More effective treatment needs to be
      identified for advanced stage UPSC.

PMID- 15581949
TI  - Localization of the VEGF and angiopoietin genes in uterine carcinosarcoma.
AB  - OBJECTIVE: Carcinosarcoma of the uterus is a highly aggressive tumor. However,
      the angiogenesis in this tumor remains unclear. This is the first study to
      examine the characteristics of angiogenesis in this tumor at the molecular level
      while also comparing the findings with those of high-grade endometrial carcinoma.
      METHODS: The expression of vascular endothelial growth factors (VEGF) and
      angiopoietins (Ang) genes were examined in 35 primary uterine carcinosarcomas as
      well as in 12 high-grade endometrial carcinomas by in situ hybridization.
      RESULTS: A strong expression of VEGF-A mRNA was significantly seen in
      carcinosarcomas compared to high-grade endometrial carcinomas. Interestingly, in
      uterine carcinosarcoma, VEGF-A mRNA was more strongly expressed in the carcinoma
      cells than in the sarcoma cells. In addition, a decrease in the VEGF-A mRNA
      expression was found in the transitional areas between carcinomatous and
      sarcomatous elements in most carcinosarcomas evaluated. Moreover, the Ang-2 mRNA
      expression was significantly seen in the vasculature adjacent to the periphery of
      the carcinoma cells in most carcinosarcomas, in comparison to that of endometrial
      carcinomas. CONCLUSIONS: A high angiogenic activity in uterine carcinosarcoma was
      shown, in comparison to that of endometrial carcinoma. Tumor angiogenesis in
      uterine carcinosarcoma might be chiefly influenced by VEGF-A in the carcinoma
      cells, in cooperation with Ang-2 in the surrounding microvessels, however, this
      is not fully usually the case in sarcoma cells.

PMID- 15581950
TI  - DNA aneuploidy is associated with increased mortality for stage I endometrial
      cancer.
AB  - OBJECTIVE: The current study was undertaken to determine if DNA ploidy is a
      useful prognostic variable for predicting recurrence in stage I endometrial
      cancer. For cancer of the endometrium, survival following recurrence may depend
      on a number of factors, including the pattern of recurrence and the response to
      second line treatment. Previous studies have demonstrated a worse survival for
      patients with DNA aneuploid tumors. It remains unclear, however, whether this is
      necessarily due to a higher risk of recurrence. This study was undertaken to
      assess DNA ploidy and risk of recurrence in patients with stage I endometrial
      cancer. METHODS: This is a retrospective study of surgically treated patients
      with stages IB and IC endometrial cancer treated from 1992 to 2000. All patients
      underwent definitive surgery, including staging lymphadenectomy. None of the
      patients received postoperative treatment. DNA ploidy was determined using flow
      cytometry and image analysis. Grade, lymph-vascular space invasion, stage (stage
      IB versus IC), and DNA ploidy were analyzed with regard to recurrence and
      survival. RESULTS: There were 100 patients with stages IB and IC endometrial
      cancer in this analysis. There were 17 recurrences (17%) and 10 patients that
      died of cancer (10%). Grade 3 and the presence of lymph-vascular space invasion
      were associated with increased risk of recurrence; DNA aneuploidy and stage were
      not. Grade, lymph-vascular space invasion, and DNA ploidy were associated with
      survival. These findings indicate that DNA aneuploidy does not increase the risk
      of disease recurrence but is associated with overall survival. CONCLUSION:
      Although the recurrence risk is not higher for patients with surgical stage I
      endometrial cancer and aneuploid tumors, overall mortality remains higher.

PMID- 15581951
TI  - Upregulation of FasL by LPA on ovarian cancer cell surface leads to apoptosis of
      activated lymphocytes.
AB  - OBJECTIVE: Constitutive expression and upregulation of FasL by malignant
      epithelial cells counterattack infiltrating natural killer (NK) cells and
      cytotoxic T lymphocytes (CTLs) and induce apoptosis of normal cells within the
      tumor, which may induce metastasis. As little is known about the mechanisms that
      regulate expression of Fas ligand and the subsequent release of FasL in
      epithelial ovarian cancer cells (EOC), we investigated the effects of
      lysophosphatidic acid (LPA) on FasL expression and associated signaling pathways.
      METHODS: We used established EOC cell lines that were incubated with or without
      LPA and FasL expression was detected by flow cytometry. Cells were additionally
      lysed and detected for total protein expression. Activated CD4+ T cells, after
      coculture with or without EOC, were collected for apoptosis staining and analysis
      by flow cytometry. RESULTS: Flow cytometry showed that LPA strongly upregulated
      FasL expression on the OVCAR3 cell surface (P < 0.01), yet in Dov13 cells, LPA
      significantly upregulated FasL expression only in the presence of the general
      matrix metalloproteinase (MMP) inhibitors GM6001 and MMP inhibitor II (P < 0.01).
      The MEK/ERK1/2 kinase cascade is required for FasL upregulation, since the MEK
      inhibitor PD98059 significantly inhibited FasL upregulation induced by LPA (P <
      0.01). Type II secretory phospholipase A2 (sPLA2-II), which promotes protein
      exocytosis from secretory vesicles and gelatinase granules, affects FasL
      translocation from intracellular to the cell surface. Pretreatment of Dov13 cells
      with LPA increased activated T cell apoptosis in cocultures. CONCLUSIONS: These
      data suggest that upregulation of FasL by LPA provides EOC immune-privilege and
      leads to apoptosis of activated T lymphocytes.

PMID- 15581952
TI  - Adjuvant therapy of completely resected dysgerminoma with carboplatin and
      etoposide: a trial of the Gynecologic Oncology Group.
AB  - OBJECTIVE: This study was designed to evaluate the effect of adjuvant
      chemotherapy with carboplatin and etoposide in patients with completely resected
      stage IB-III dysgerminoma. METHODS: Eligible patients were treated with three
      courses of carboplatin 400 mg/m(2) on day 1 plus etoposide 120 mg/m(2) on days 1,
      2, and 3 every 4 weeks for three courses. RESULTS: Forty-two patients were
      entered on this trial, of whom 39 were eligible. No patient suffered a recurrence
      of dysgerminoma, but one patient ultimately died of lung adenocarcinoma. One
      patient was excluded on pathology review (elements of endodermal sinus tumor were
      present) developed recurrent tumor and died despite further therapy. As expected,
      the regimen was well tolerated. Median follow-up of surviving patients is 7.8
      years (range: 2.86 months to 10.92 years). CONCLUSION: The regimen used in this
      study is an alternative to cisplatin, etoposide, and bleomycin (BEP) for selected
      patients for whom minimizing toxicity (particularly neuropathy) is critical or
      for whom reduction in the number of treatment days is important.

PMID- 15581953
TI  - Apoptosis-related proteins and cervical intraepithelial neoplasia in human
      immunodeficiency virus-seropositive women.
AB  - OBJECTIVE: To evaluate the expression of bcl-2, p-53, Ki-67, and apoptosis as
      evidenced by nuclear DNA fragmentation in cervical biopsies obtained from human
      immunodeficiency virus (HIV)-seropositive and HIV-seronegative women with a
      history of intravenous drug abuse. METHODS: We investigated 109 consecutive
      cervical biopsies (73 from HIV seropositive and 36 from HIV seronegative
      patients), including 86 cervical intraepithelial neoplasia (CIN) lesions and 23
      normal cervical epithelium. The markers of apoptosis and proliferation were
      detected using immunostaining methods on paraffin sections. The associations
      between HIV status and the intensities of immunostaining were tested by
      univariate and multivariable methods. RESULTS: The severity of CIN correlated
      directly with the intensities of p-53 (Spearman Rho = 0.19; P = 0.05) and Ki-67
      immunostaining (Spearman Rho = 0.46, P < 0.001) and with apoptosis and Bcl-2
      expression (chi-square for trend = 10.6 and 3.91 , P < 0.001 and P = 0.048,
      respectively).After adjustment, by logistic regression analysis, for the
      potential confounding effect of severity of CIN and Human Papillomavirus (HPV)
      infection, apoptosis was five times more common in cervical biopsies of HIV
      seropositive compared to HIV seronegative patients (27 out of 73 as compared to 4
      out of 36, adjusted Odds Ratio = 5.0; 95% confidence intervals = 1.56-16.33, P =
      0.007). The adjusted odds ratio of increasing p53 immunodetection was
      significantly higher in biopsies obtained from HIV-seropositive patients compared
      to HIV seronegative controls (OR = 8.7; 95% confidence intervals = 2.97-25.3, P <
      0.0001). CONCLUSION: Markers of apoptosis such as nuclear DNA fragmentation and p
      53 immunoreactivity are more intensely expressed in cervical biopsies of normal
      and dysplastic epithelium of HIV-seropositive compared to HIV-seronegative women.

PMID- 15581954
TI  - Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology
      Group study.
AB  - OBJECTIVES: To assess the activity of vinorelbine in women with recurrent or
      resistant epithelial ovarian cancer following treatment with platinum and
      paclitaxel in terms of survival rate at 6 months, objective response rate (in the
      subset of patients with bidimensionally measurable disease), and health-related
      quality of life. METHODS: Seventy-nine evaluable patients with progressive
      ovarian cancer following platinum and taxane therapy received vinorelbine 30
      mg/m(2) days 1 and 8 of a 21-day treatment cycle. RESULTS: Six-month survival
      rate for the entire group was 65% (95% CI: 54-75%) and median survival was 10.1
      months (95% CI: 7.7-13.6 months). In the 71 women with measurable disease, 0
      complete and 2 partial responses were observed (RR = 3%) (95% CI: 0.3-10%).
      Patients reported substantial symptom-related distress at baseline, which
      persisted, but did not worsen, during treatment. Patients also had impaired
      physical functioning at baseline and this continued to decline during treatment.
      CONCLUSIONS: The 6-month survival rate achieved with salvage vinorelbine is
      comparable to the results obtained with other salvage therapies in patients with
      relapsed ovarian cancer. During the initial 10 weeks of treatment, vinorelbine
      did not appear to be effective in alleviating the symptom-related distress or
      progressive impairment of physical functioning associated with this disease.

PMID- 15581955
TI  - The use of colorectal stents for palliation of large-bowel obstruction due to
      recurrent gynecologic cancer.
AB  - OBJECTIVE: Acute large-bowel obstruction (LBO) is considered a surgical
      emergency. In gynecologic oncology patients with LBO due to recurrent tumor,
      surgery has been the standard treatment. However, operative intervention has
      significant associated morbidity and mortality. Recent reports have addressed the
      use of colorectal stents for the treatment of colonic malignancies. We are
      reporting our experience with colorectal stents in gynecologic oncology patients.
      METHODS: We reviewed the records of all patients who underwent colorectal stent
      placement for palliation of LBO due to recurrent gynecologic malignancy from
      August 2001 to January 2003. RESULTS: Six patients were identified; five patients
      had recurrent ovarian cancer and one had recurrent endometrial cancer. The mean
      age of the six patients at the time of stent placement was 51.5 years (range, 22
      83 years). The length of LBO ranged from 2 to 10 cm. Two patients had a lumen of
      1 to 2 mm before stent placement, while the other four had a complete obstruction
      and needed balloon dilatation before the deployment of the stent. Four (67%) of
      six patients had immediate relief, with passage of stool and flatus noted at the
      time of the colorectal stent placement. Stent placement failed to relieve the LBO
      in two patients (33%); these patients went on to receive colostomies. Of the four
      patients who had successful stent placement, the mean survival after stent
      placement was 120 days. One patient had a contained sigmoid bowel perforation
      noted 12 days after stent placement, which resolved with conservative measures.
      CONCLUSION: Colonic stents appear to be a useful option in the management of
      patients with LBO due to recurrent gynecologic malignancy.

PMID- 15581956
TI  - The relationship between expression of Ku70 and survival in irradiated patients
      with endometrial carcinoma.
AB  - OBJECTIVE: To investigate the prognostic value of Ku70 protein expression in
      patients with endometrial cancer and to examine the correlation between Ku70
      expression and established prognostic factors. METHODS: Ku70 immunoreactivity was
      determined by an immunohistochemical technique in a series of 81 patients with
      stages I-III primary endometrial carcinoma. The prognostic value of Ku70
      expression was also studied in 74 patients who had been followed for at least 1
      year or until death. RESULTS: The median percentage of Ku70 expression was 80%.
      The established clinicopathological prognostic factors for endometrial carcinoma
      were not associated with Ku70 expression. Although disease-free survival was
      significantly higher in patients with lower levels than median value of Ku70 (P <
      0.05), overall survival was not different. In the univariate analysis, Ku70
      expression did not show significant prognostic value for overall survival. The
      multivariate analysis also showed that Ku70 expression was not related to
      patient's outcome (P = 0.51, relative risk = 0.27, 95% confidence interval = 0.10
      1.92). CONCLUSIONS: Our results suggest that Ku70 expression may not be a
      prognostic marker in endometrial carcinoma patients. However, disease-free
      survival was significantly higher in patients with low percentage of Ku70
      positive tumor cells. More studies are needed to evaluate the correlation between
      Ku70 and survival in patients with endometrial cancer.

PMID- 15581957
TI  - Expression of cyclooxygenase-2 in adenocarcinomas of the uterine cervix and its
      relation to angiogenesis and tumor growth.
AB  - OBJECTIVE: The purpose of this study was to evaluate cyclooxygenase (COX)-2
      expression in adenocarcinomas of the uterine cervix and its correlation with
      clinicopathologic features, angiogenesis, and tumor growth. METHODS: Thirty-nine
      cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were
      examined by immunohistochemical studies with anti-COX-2. Microvessels were
      immunohistochemically labeled with an antibody to CD34. Computerized image
      analysis was used to evaluate microvessel density (MVD). The apoptotic cells were
      visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end
      labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67
      antibody. RESULTS: Twenty-eight tumors (71.8%) were classified as COX-2 positive.
      COX-2 expression correlated with FIGO stage (P < 0.01). Tumors expressing COX-2
      had a significantly higher MVD and Ki-67 index than those that did not express
      COX-2 (P < 0.05). However, COX-2 expression did not correlate with the apoptotic
      index. In univariate long-rank analysis, COX-2 expression, MVD, and FIGO stage
      were associated with shortened survival. However, FIGO stage and MVD were the
      only independent prognostic factors by multivariate analysis. CONCLUSIONS: Our
      results suggest that COX-2 expression in cervical adenocarcinomas may contribute
      to tumor progression by increasing angiogenesis and cell proliferation.

PMID- 15581958
TI  - Ovarian tumor expression of an oviductal protein in the hen: a model for human
      serous ovarian adenocarcinoma.
AB  - OBJECTIVE: We hypothesized that ovarian tumors without oviductal involvement
      would not express the oviductal protein ovalbumin, the major protein found in the
      magnum of the hen's oviduct. METHODS: On the basis of gross visual examination,
      tissues samples were removed from hens determined to have ovarian tumors and were
      processed, embedded in paraffin, sectioned, mounted on glass slides, and stained
      with hematoxylin and eosin. Ovarian tumors and other peritoneal lesions were
      evaluated histologically. Paraffin sections of ovarian and oviductal tissue were
      deparaffinized and evaluated for the protein expression of ovalbumin,
      proliferating cell nuclear antigen (PCNA), and progesterone receptor (PR).
      RESULTS: Hens with ovarian adenocarcinoma without (n = 10) or with (n = 6)
      oviductal involvement were positive for ovalbumin in the ovary. Ovary sections
      from normal hens (n = 9) were negative, and oviductal sections from normal hens
      (n = 3) were positive for ovalbumin. Expression of PCNA protein was abundant in
      all ovarian tumors (16 of 16). Oviductal epithelial cells strongly expressed PCNA
      protein. Expression of PR was observed in 9 of 14 ovarian tumors. CONCLUSION: The
      presence of ovalbumin in ovarian tumors in the absence of any oviductal
      involvement suggests that ovarian tumors dedifferentiate during the disease
      process and thereby resemble serous-type ovarian tumors in women.

PMID- 15581959
TI  - A fertility-sparing alternative to radical hysterectomy: how many patients may be
      eligible?
AB  - OBJECTIVE: To determine the percentage of patients with early-stage cervical
      cancer who may be eligible for fertility preservation with laparoscopic radical
      vaginal trachelectomy (LRVT). METHODS: We retrospectively reviewed the records of
      patients who underwent a radical hysterectomy for invasive cervical cancer at our
      institution from 12/85 to 8/01, before our use of LRVT at Memorial Sloan
      Kettering Cancer Center. Institutional eligibility criteria for LRVT were
      applied. Patients > or =40 years of age were considered ineligible. RESULTS: We
      identified 435 patients who had undergone radical hysterectomy for cervical
      cancer; 186 were age < 40 at surgery and constituted our study population. Eighty
      nine (48%) patients may have been eligible by our pathologic criteria. In 12
      patients, LRVT may have been aborted or altered because of unexpected disease
      spread. CONCLUSION: A significant number of patients < 40 with early-stage
      cervical cancer may be pathologically eligible for LRVT and should be counseled
      on this preoperatively.

PMID- 15581960
TI  - Response of combination platinum and gemcitabine chemotherapy for recurrent
      epithelial ovarian carcinoma.
AB  - OBJECTIVE: It has been postulated that gemcitabine inhibits DNA repair, and
      platinum resistance is due to increased DNA repair activity. The addition of
      gemcitabine to platinum-based agents may have synergistic tumoricidal activity.
      METHODS: Retrospective chart review of all patients with recurrent, persistent,
      or progressive fallopian tube or ovarian carcinoma treated with a platinum-based
      compound and gemcitabine from 2001 to present was performed. RESULTS: Twenty-nine
      patients on second to eight line chemotherapy met inclusion criteria. The median
      age was 53 years. Twenty-two patients received cisplatin and gemcitabine, and 7
      patients received carboplatin and gemcitabine based on results of chemoresistance
      assays or prior chemorelated toxicities. The intent to treat was with six cycles
      of gemcitabine (1000 mg/m(2)) and either cisplatin (75 mg/m(2)) or carboplatin
      (AUC 5) day 1 and gemcitabine only on day 8 of a 21-day cycle. The median number
      of cycles administered was six. There were 20 grade 3 and 4 toxicities and 63% of
      patients by cycle 6 needed erythropoietin marrow support and 19% needed GCSF
      support by cycle 4. Twenty-one patients required discontinuation of day 8 that
      most commonly occurred at cycle 4. Eleven (38%) had CR, 5 (17%) had PR, 6 (21%)
      had SD, and 7 (24%) had PD, which is a 55% overall response. Nineteen of 29
      patients (66%) showed platinum resistance to initial therapy. Of those, four
      (21%) had CR, four (21%) had PR, six (32%) had SD, and five (26%) with PD, which
      demonstrates a 42% overall response rate for this particular subset of patients.
      CONCLUSIONS: Adjuvant combination platinum-based agent with gemcitabine is a very
      effective and well-tolerated treatment for recurrent fallopian tube or ovarian
      carcinoma; even in those who exhibit initial platinum resistance.

PMID- 15581961
TI  - Prospective evaluation of FDG-PET for detecting pelvic and para-aortic lymph node
      metastasis in uterine corpus cancer.
AB  - OBJECTIVES: To estimate the sensitivity and specificity of positron emission
      tomography (PET) with 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) for detecting
      pelvic and para-aortic lymph node metastasis in patients with uterine corpus
      carcinoma before surgical staging. METHODS: Patients with newly diagnosed FIGO
      grade 2 or 3 endometrioid, papillary serous, or clear cell adenocarcinoma or
      uterine corpus sarcoma scheduled for surgical staging, including bilateral pelvic
      and para-aortic lymphadenectomy, were eligible. PET was performed within 30 days
      of surgery and interpreted independently by two nuclear medicine physicians. The
      imaging, operative, and pathologic findings for each patient and each nodal site
      were compared, and the sensitivity and specificity of FDG-PET in predicting nodal
      metastasis were determined. RESULTS: Twenty patients underwent FDG-PET before
      surgical staging. One patient found to have ovarian carcinoma on final pathology
      was excluded. Of the 19 primary intrauterine tumors, 16 (84%) exhibited increased
      FDG uptake. One patient did not undergo lymphadenectomy; her chest CT was
      suspicious for metastatic disease and FDG-PET showed uptake in multiple nodal and
      pulmonary foci. Metastatic disease was confirmed by percutaneous nodal biopsy. A
      total of three pathologically positive nodes were found in 2 of the 18 patients
      (11%). FDG-PET predicted that 3 patients would have positive lymph nodes (2 true
      positive and 1 false positive). Analyzed by lymph node regions, FDG-PET had 60%
      sensitivity and 98% specificity. The sensitivity and specificity by individual
      patient were 67% and 94%, respectively. CONCLUSIONS: FDG-PET is only moderately
      sensitive in predicting lymph node metastasis pre-operatively in patients with
      endometrial cancer. This imaging modality should not replace lymphadenectomy, but
      may be helpful for patients in whom lymphadenectomy cannot be, or was not,
      performed.

PMID- 15581962
TI  - The use of transrectal ultrasound to biopsy pelvic masses in women.
AB  - OBJECTIVES: The goal of this study was to review our experience with transrectal
      ultrasound (TRUS)-guided biopsies in women with a pelvic mass, with respect to
      obtaining an adequate sample, the influence of biopsy results on patient
      management, and patient tolerance. STUDY METHODS: We conducted a chart review of
      all women at the Princess Margaret Hospital (PMH) that had been clinically
      referred for TRUS-guided biopsies of a pelvic mass. Data collected included
      patient age, previous type of malignancy, size and location of lesion being
      biopsied, postbiopsy diagnosis, and subsequent management. Statistics were purely
      descriptive. RESULTS: Eight women have had this procedure at PMH. The smallest
      size of lesion biopsied was 1.7 x 1.4 x 2.3 cm. In all eight women, the tissue
      obtained was adequate for the determination of a histological diagnosis and
      subsequently influenced patient management. The procedure was well tolerated and
      there were no complications. CONCLUSION: TRUS-guided biopsy of a pelvic mass is a
      feasible method of establishing a pathological diagnosis. In this small series of
      patients, it was found to be accurate, well tolerated, and useful in guiding
      patient management. In selected patients, the TRUS biopsy provides a useful
      alternative to transabdominal and transvaginal biopsy.

PMID- 15581963
TI  - The effect of methylenetetrahydrofolate reductase polymorphism C677T on cervical
      cancer in Korean women.
AB  - OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) gene is associated with
      DNA hypomethylation, an established hallmark of human cancer cells. The aim of
      this study was to examine the effect of MTHFR polymorphism C677T on cervical
      carcinogenesis in the context of other environmental factors, such as smoking,
      parity, and age at the first intercourse. METHODS: The study subjects were
      patients who were pathologically diagnosed with cervical neoplasia and who had a
      positive result for human papillomavirus (N = 462), and they were compared to
      normal healthy women as normal controls (N = 454). Genotypes of the patients and
      control samples were assayed by single base primer extension assay using SNapShot
      assay kit. RESULTS: Compared with MTHFR C/C, the odds ratio (95% confidence
      interval) for MTHFR T/T was 1.4 (0.9-2.3) for invasive cervical cancer and 1.3
      (0.8-2.3) for cervical intraepithelial neoplasia (CIN) II or III. The risks for
      invasive cervical cancer were higher with less than 40 years old at diagnosis
      (2.1, 1.0-4.3), than with over 40 years old at diagnosis (1.2, 0.7-2.2). Current
      smoking women with early onset with MTHFR T/T had a 4.7 (0.6-36.2) times higher
      risk of cervical cancer. The risks of MTHFR T/T or C/T also increased for women
      with an early age of first intercourse or for women with two or more children, as
      compared with MTHFR C/C. CONCLUSION: Polymorphisms of MTHFR are associated with a
      higher risk of developing cervical cancer, and in particular for an early onset
      of cervical carcinogenesis.

PMID- 15581964
TI  - Retrospective analysis of weekly topotecan as salvage therapy in relapsed ovarian
      cancer.
AB  - OBJECTIVE: To retrospectively investigate the safety and efficacy of weekly
      topotecan in heavily pretreated patients with ovarian cancer. METHODS: Data were
      collected by retrospective review of patient records. Eligible patients had
      received > or =2 prior regimens for ovarian cancer before treatment with weekly
      topotecan. Efficacy was determined by measurable disease or CA 125 levels.
      Adverse event and growth factor support data were also collected. RESULTS: Fifty
      patients (median age, 61 years) were evaluable for safety and received a total of
      244 4-week cycles of therapy (median, 3; range, 1-21 cycles). Most patients (84%)
      had measurable disease, and 30% had performance status of > or =2. Patients had
      received two to six prior treatments for ovarian cancer. Median weekly dose per
      patient was topotecan 3.7 mg/m(2). Grade 4 hematologic toxicities (generally
      manageable) occurred in 4% of patients. One patient had febrile neutropenia.
      Grade 3/4 nonhematologic toxicities were fatigue in two (4%) patients. Forty-two
      patients were evaluable for response. Of 35 evaluable patients with measurable
      disease, 11 (31%) had a partial response (median duration, 3 months), and 15
      (43%) patients had stable disease (median duration, 3.5 months). Of 41 evaluable
      patients with elevated CA 125 (median, 154 U/l; range, 47-7200 U/l), 11 (27%) had
      > or =50% decreases or normalization of CA 125 levels. Median time to progression
      in all patients with stable disease has not been reached (follow-up range, 1.5
      17.3 months). CONCLUSIONS: Weekly topotecan is active and well tolerated in
      heavily pretreated patients with relapsed ovarian cancer. Prospective studies of
      this regimen are warranted.

PMID- 15581965
TI  - Her-2/neu expression and amplification in early stage ovarian surface epithelial
      neoplasms.
AB  - OBJECTIVE: The aim of this study is to examine Her-2/neu gene amplification and
      protein overexpression in a spectrum of ovarian neoplasms using both
      immunohistochemical (IHC) and fluorescence in situ hybridization (FISH)
      techniques that are FDA approved. This study is focused on early stage tumors
      including both carcinomas and borderline tumors. METHODS: FDA-approved IHC and
      FISH for Her-2/neu were performed on formalin-fixed, paraffin-embedded tissue
      from 79 ovarian neoplasms representing a broad spectrum of tumor types as well as
      four normal ovaries. All tumors were either stage I or stage II. Tumor and normal
      tissue were studied collectively using a tissue microarray (TMA). HercepTest
      (DAKO) and PathVysion Her-2/neu probe kit (Vysis Inc.) were used for IHC and FISH
      analysis. RESULTS: FISH analysis of serous carcinomas demonstrated Her-2/neu gene
      amplification in 3 (18%) of 17 cases. Two of three cases showing Her-2/neu gene
      amplification were scored 1+ using IHC, while the remaining case was scored as 0.
      Analysis of endometrioid carcinomas demonstrated Her-2/neu amplification using
      FISH in 1 of 10 (10%) cases. IHC in this case was scored 2+ (positive). None of
      the remaining 44 tumors, including clear cell carcinoma (n = 12), transitional
      cell carcinoma (n = 1), mixed epithelial carcinoma (n = 7), carcinoma not
      otherwise specified (n = 1), and 31 borderline tumors (mucinous, n = 17;
      endometrioid, n = 7; serous, n = 7), showed Her-2/neu gene amplification or
      protein overexpression. Normal ovaries were negative as well. CONCLUSIONS:
      Amplification of Her-2/neu in early stage ovarian neoplasms is infrequent, 6.7%
      overall. Due to the limited number of informative cases, we were unable to
      determine the clinical significance of Her-2/neu amplification in this study. Her
      2/neu amplification was restricted to carcinomas and was not encountered in
      ovarian borderline tumors.

PMID- 15581966
TI  - Neoadjuvant high-dose intraarterial infusion chemotherapy under percutaneous
      pelvic perfusion with extracorporeal chemofiltration in patients with stages IIIa
      IVa cervical cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the response rate and
      survival of patients with locally advanced uterine cervical cancer who were
      treated with intraarterial infusion chemotherapy under percutaneous pelvic
      perfusion with extracorporeal chemofiltration (PPPEC). METHODS: Twenty-three
      untreated patients with stages IIIa-IVa cervical cancer were enrolled in the
      study. PPPEC was administered twice at 2 weeks interval using high-dose cisplatin
      alone (140-250 mg/m(2)) or high-dose cisplatin plus mitomycin C (7 mg/m(2)),
      pepleomycin (7 mg/m(2)) and 5-fluorouracil (700 mg/m(2)). Eighteen patients in
      whom the tumor downstaging was confirmed underwent radical surgery following
      PPPEC, whereas in the remaining five patients, radiotherapy was administered.
      RESULTS: Two weeks after the second PPPEC, the median volumetric tumor reduction
      and tumor response were 76% and 87%, respectively. Histologic response was 96%,
      while the tumor downstaging reached 83%. The curative surgery rate achieved was
      89%. Five-year progression-free survival was 47% and 5-year survival rate was
      74%. CONCLUSION: High-dose intraarterial infusion chemotherapy under PPPEC
      effectively achieved tumor downstaging and resulted in the favorable performance
      of the subsequent radical surgery and improved the 5-year survival rate of
      patients with locally advanced uterine cervical cancer.

PMID- 15581967
TI  - ERBB-2 gene overexpression and amplification in uterine sarcomas.
AB  - BACKGROUND: The aim of this study was to determine ERBB-2 (HER-2/neu) gene
      alterations in different subtypes of uterine sarcomas. METHODS: After central
      review, representative biopsies were immunohistochemically stained and
      semiquantitatively scored as negative, weakly (1+), moderately (2+), or strongly
      (3+) positive. Subsequently, fluorescence in situ hybridization (FISH) was
      performed on cases with 2+ and 3+ expression. RESULTS: Seventy tumors (52
      primaries and 18 recurrent) were evaluated. All 10 adenosarcomas, 21 endometrial
      stromal sarcomas, and 10 leiomyosarcomas were negative both in the primary and
      recurrent setting. Twenty-two primary carcinosarcomas were scored. The epithelial
      component was negative/1+ in 16 (73%), 2+/3+ in five (22.5%) tumors, and could
      not be evaluated in one case (4.5%), whereas the sarcoma component stained
      negative/1+ in 21 cases (95.5%) and 3+ (4.5%) in one case. In two recurrent
      carcinosarcomas, the epithelial component stained 3+ in both cases, whereas the
      sarcoma component scored negative and 1+. Amplification of the ERBB-2 gene as
      determined by FISH was observed in 3/7 (43%) carcinosarcomas with 2+ or 3+
      overexpression, resulting in an overall 3/22 (14%) amplification rate. One out of
      four undifferentiated uterine sarcomas stained 2+. ERBB-2 immunopositivity (3+)
      and ERBB-2 amplification by FISH were confirmed in the recurrent tumor, resulting
      in a gene amplification rate of 1/4 in undifferentiated uterine sarcomas.
      CONCLUSION: The current results suggest absence of ERBB-2 overexpression in
      uterine leiomyosarcoma, uterine adenosarcoma, and endometrial stromal sarcoma,
      whereas the ERBB-2 gene might have a biologic role in uterine carcinosarcoma and
      undifferentiated uterine sarcomas.

PMID- 15581968
TI  - Morbid obesity and endometrial cancer: surgical, clinical, and pathologic
      outcomes in surgically managed patients.
AB  - OBJECTIVE: To evaluate surgical, clinical, and pathologic outcomes of patients
      with endometrial cancer managed with primary surgery when stratified by body mass
      index (BMI). METHODS: A review of 356 consecutive patients undergoing primary
      surgical management of endometrial carcinoma by a single gynecologic oncology
      service from 1997 to 2003 was undertaken. Patients were divided into three groups
      based on preoperative BMI. Data regarding surgical and pathologic outcomes were
      compared. RESULTS: Twenty-two percent of patients had a BMI >40, 38% were 30-40,
      and 40% were <30. Overall, 90% underwent some surgical staging, including 93%,
      92%, and 81% of those with a BMI <30, 30-40, and >40, respectively. In fully
      staged patients, a median 23 lymph nodes were removed in all groups, without a
      significant difference in the number of aortic nodes recovered between the
      heaviest and lightest groups. Aortic lymphadenectomy was performed in 48%
      patients with BMI >40 compared with 74% of patients with BMI <30. Intraoperative
      and postoperative complications were rare and similar between groups. Patients
      with BMI >40 were more commonly diagnosed with grade 1 tumor than patients with
      BMI <30. Rates of nodal metastasis were similar between groups and occurred in
      11% of patients overall. In those with a BMI >40, extrauterine disease was
      encountered in 12% of patients. CONCLUSIONS: While surgical staging of morbidly
      obese patients is difficult, adequate lymphadenectomy can be performed safely;
      although aortic nodes are less commonly resected in this population. Staging
      remains important in obese women, as the risk of extrauterine disease, including
      lymph node metastasis, is similar to that in women with ideal body weight.

PMID- 15581969
TI  - Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the
      endometrium.
AB  - OBJECTIVE: The purpose of this study was to evaluate patients with uterine
      papillary serous carcinoma (UPSC), clear cell (CC), and grade 3 endometrioid (G3)
      surgically stage I endometrial cancer. METHODS: The 25th Annual Report (AR) of
      FIGO was used to identify patients with endometrial cancers who were surgically
      staged. For comparison, all cancers reported were evaluated with particular
      interest in patients with stage I UPSC, CC, and G3. Incidence, substage, post
      surgical treatment, and survival were identified. RESULTS: Of 5694 endometrial
      cancer patients reported to the AR, 3996 (70%) were surgically stage I. There
      were 148 UPSC, 59 CC, and 325 with G3 lesions. UPSC and CC represent 5.2% of all
      stage I cancers while 8.1% are G3. Although there were greater number of UPSC,
      CC, and G3 with extrauterine disease, about 50% of UPSC and CC were stage I. This
      compares to 81% for G1, 68% for G2, and only 42% for G3. There were more IA
      cancers with UPSC and CC than G3 (22%, 33%, and 17%, respectively). Survival (5
      years) for UPSC and CC was 72% and 81%, respectively, compared to 76% for G3
      lesions. Postoperative radiation improved survival somewhat (6-8%) but the
      difference was not significant. CONCLUSION: UPSC and CC histotypes when diagnosed
      as stage I have a better survival than commonly perceived and equal to G3
      endometrioid cancers. Postoperative radiation improves survival but not
      significantly so. The role of chemotherapy has not been defined.

PMID- 15581970
TI  - Metabolic monitoring of advanced uterine cervical cancer neoadjuvant chemotherapy
      by using [F-18]-Fluorodeoxyglucose positron emission tomography: preliminary
      results in three patients.
AB  - OBJECTIVE: The aim of this report is to describe the potential clinical utility
      of tracer [F-18]-Fluorodeoxyglucose (FDG) uptake, quantitated as a standardized
      uptake value (SUV) by positron emission tomography (PET), to evaluate treatment
      response to neoadjuvant chemotherapy (NAC) in advanced uterine cervical cancer.
      METHODS: We briefly describe the clinical courses of three women with advanced
      cervical cancer who were treated with neoadjuvant chemotherapy (NAC) prior to
      radical hysterectomy and who were analyzed for correlation with the decrease in
      tumor volume by magnetic resonance imaging (MRI), in SUV by FDG-PET, and by
      histologic response. RESULTS: In these individuals, tumor volume and SUV were
      decreased by NAC. The decrease in SUV by FDG-PET was better correlated to
      histologic response for NAC than MRI was in advanced cervical cancer.
      CONCLUSIONS: Measurement of SUV by FDG-PET has clinical utility in evaluating
      treatment response for NAC in advanced cervical cancer. Although work in this
      field is still in the early stages, this report demonstrates that SUV by FDG-PET
      has the potential to become the new standard for monitoring the treatment
      response of NAC in cervical cancer. This monitoring approach must be proven in a
      larger number of patients for both primary and secondary lesions and should be
      further explored in another gynecologic cancer.

PMID- 15581971
TI  - Expression status and mutational analysis of the ras and B-raf genes in ovarian
      granulosa cell and epithelial tumors.
AB  - OBJECTIVES: The molecular pathogenesis of granulosa cell tumors of the ovary
      (GCT) is not understood. Activating mutations in the K-, N-, and H-ras
      protooncogenes have been identified in a wide range of human cancers, including
      ovarian epithelial tumors. Furthermore, an apparent association has recently been
      reported between the presence of ras and B-raf mutations in the same cancer
      types. Activation of the ras/raf pathway would be predicted to be tumorigenic in
      granulosa cells. METHODS: Gene expression patterns of the three ras and B-raf
      genes were determined in a panel of GCT and ovarian epithelial tumors, and in
      normal premenopausal ovaries. Expression was determined by RT-PCR using gene
      specific primers combined with Southern blot analysis of the PCR products using
      gene-specific (32)P-labeled probes. Direct sequence analysis was used to screen
      for known activating mutations. RESULTS: Widespread expression of the four genes
      was observed in all tumor types examined. Compared to the normal ovaries, none of
      the genes was expressed at significantly higher levels in any of the tumor types
      examined. A heterozygous point mutation in codon 12 of the K-ras gene was found
      in five of the 10 mucinous tumors. No B-raf mutations were detected in the
      mucinous tumors. No mutations were detected in any of the genes in the cohort of
      GCT. CONCLUSION: These results suggest that neither overexpression nor activating
      mutations of the ras or B-raf genes are associated with the development of GCT.

PMID- 15581972
TI  - Comparison of gene expression in squamous cell carcinoma and adenocarcinoma of
      the uterine cervix.
AB  - OBJECTIVES: Microarray expression analysis of cervical tumors has revealed
      differential expression of genes that may be useful as markers or targets for
      treatment. We question the application of array findings across the major
      categories of cervical cancer. We sought to identify differences between normal
      squamous epithelium (NSQ) and glandular epithelium (NGL) of the uterine cervix
      and their malignant variants: squamous cell cancer (SCC) and adenocarcinoma
      (ACA). METHODS: Eight genes were selected: 12-lipoxygenase (12-LOX), keratin 4,
      trypsinogen 2 (TRY2), Rh glycoprotein C (RhGC), collagen type V alpha 2, integrin
      alpha 5, integrin alpha 6, and c-myc. Ten cases each of SCC and ACA of the cervix
      were selected from our tumor bank. NSQ and NGL epithelia were obtained from
      consecutive patients undergoing surgery for benign disease. RNA extraction, cDNA
      synthesis, and DNA amplification of all samples were performed according to an
      established protocol. Electrophoresis of the multiplexed polymerase chain
      reaction (PCR) products was performed under standard conditions, followed by
      digital image capture. A ratio of target to control gene (beta-actin) was
      obtained for each sample. Analysis of variance was applied to the mean ratios for
      each tissue to establish significant differences. Individual pairwise comparisons
      were made by Student t tests and verified with the Tukey-Kramer test. RESULTS:
      Clinically valid comparisons are NSQ to NGL, NSQ to SCC, NGL to ACA, and SCC to
      ACA. Various expression patterns were observed between the epithelia and their
      malignant phenotypes. Significant differences in gene expression were observed
      between benign squamous and glandular epithelium in four of the eight genes and
      between malignant squamous and glandular epithelium in three of the eight genes.
      Significant differences in gene expression between benign and malignant tissues
      were demonstrated in four of the eight genes. CONCLUSIONS: We have defined
      significant differential expression changes between the two principal cervical
      tumor types. Differences in genes are demonstrated and must be considered if
      array technology is applied to the study of the biologic behavior of these tumors
      as well as their screening and management. The observed differential expression
      should be a compelling argument to perform type-specific expression analysis for
      other tumors with histological variants.

PMID- 15581973
TI  - Human papillomavirus DNA detection and histological findings in women referred
      for atypical glandular cells or adenocarcinoma in situ in their Pap smears.
AB  - OBJECTIVE: To evaluate the association between high-risk human papillomavirus
      (HPV) DNA detection and histological diagnosis in women referred for atypical
      glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In
      this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade
      squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA
      using Hybrid Capture II (HC II). All women underwent colposcopic examination, and
      cervical biopsy was performed for 95 patients. Fifty-one women referred due to
      AGC with normal colposcopy and normal second Pap smear were scheduled for control
      visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV
      DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of
      women with AIS Pap smear, being significantly higher when compared with the
      prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically
      significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected
      in only 16% of the women without significant abnormalities in biopsy, in contrast
      to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five
      percent of women with invasive cervical carcinoma (squamous or adenocarcinoma)
      tested positive for HPV DNA. HPV DNA detection was significantly associated with
      histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI
      14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the
      severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in
      their Pap smear. These data implicate the use of HPV testing in triage of women
      with AGC Pap smears.

PMID- 15581974
TI  - A phase II trial of weekly docetaxel in patients with platinum-resistant
      epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer.
AB  - OBJECTIVE: To determine the activity and tolerability of weekly docetaxel in
      patients with platinum-resistant mullerian origin tumors. METHODS: Patients with
      persistent disease, or those recurring less than 6 months after receiving
      platinum-containing therapy, were eligible for this phase II study. Docetaxel was
      initially administered at a dose of 40 mg/m(2) on days 1, 8, and 15, with a cycle
      length of 28 days. This starting dose was subsequently reduced to 30 mg/m(2) due
      to toxicity. Dexamethasone prophylaxis was administered at a dose of 4 mg PO
      every 12 hours for 3 doses, starting 12 hours before each dose of docetaxel.
      RESULTS: Thirty-two patients were enrolled, with a median age of 59 years. The
      majority of patients received a median of 3 prior regimens, with 45% of the study
      group having received 4 or more prior regimens. The overall response rate in 29
      evaluable patients was 6.9%, with no complete responses. Seventeen percent of
      patients experienced stable disease. Dose reduction or delay was required in 10
      of the first 22 patients enrolled, prompting a reduction in the starting dose to
      30 mg/m(2). Hematologic toxicity was generally tolerable, and no patient
      experienced febrile neutropenia. Non-hematologic toxicity was generally grade 1
      in nature, although a combination of multiple low grade toxicities occurring in
      an individual patient oftentimes mandated dose reduction. CONCLUSIONS: Weekly
      docetaxel demonstrated modest activity in a heavily pre-treated, platinum
      resistant population. A starting docetaxel dose of 30 mg/m(2) would be reasonable
      for future studies exploring the utility of weekly dosing in less heavily pre
      treated patients.

PMID- 15581975
TI  - Treatment and recurrence patterns in endometrial stromal sarcomas and the
      relation to c-kit expression.
AB  - INTRODUCTION: Endometrial stromal sarcomas (ESS) are a rare gynecologic
      malignancy. The optimal management of this cancer remains unclear, although
      previous reports have failed to demonstrate a clear benefit to adjuvant
      chemotherapy or radiation. With the successful application of directed biological
      therapy in other sarcomas, a review of the behavior and biology of this disease
      is warranted. OBJECTIVES: To review outcomes and patterns of failure in patients
      with endometrial stromal sarcoma diagnosed over 31 years at our institution and
      the relationship to protooncogene c-kit expression. MATERIALS AND METHODS:
      Hospital records and pathology were reviewed for 28 patients with endometrial
      stromal sarcomas [19 low-grade (LGESS) and 9 high-grade (HGESS)] treated between
      1972 and 2003. Archival tissue samples from 16 patients were available and
      stained with CD 117 (c-kit) antibody (1:25 dilution). Staining intensity was
      graded 1+ to 3+ and distribution of the cellular staining as focal (10-30% of the
      cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells).
      Positive tumors had more than 10% of cells comprising the neoplasm display
      immunoreactivity. RESULTS.: We found a significant difference in 5-year overall
      survival between LGESS and HGESS (P = 0.001). There was no significant difference
      in overall survival for patients with local versus advanced disease (P = 0.53) or
      in overall survival for those who underwent lymphadenectomy and those who did not
      (P = 0.92). 50% of patients received postoperative radiation with no difference
      in disease-free or overall survival (P = 0.68 and P = 0.53). Ten patients
      relapsed (36%, four HGESS and six LGESS). Seven of sixteen (43.8%) tumor samples
      expressed detectable c-kit. Five of seven (71%) were HGESS, and the other two
      (22%) were LGESS tumors. The median survival of patients with c-kit-positive
      versus c-kit-negative tumors was 12 and 47 months, respectively. CONCLUSIONS:
      This study confirms the superior overall prognosis of LGESS relative to HGESS,
      despite the similar rates of relapse. Although hard to assess, due to population
      heterogeneity and small numbers, adjuvant chemotherapy and radiation appear to be
      of limited benefit. Expression of c-kit was common, especially in high-grade
      lesions and may represent a potential therapeutic target.

PMID- 15581976
TI  - Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line
      Ishikawa: inhibition of growth and angiogenic factors.
AB  - BACKGROUND: A high level of estrogen receptor-alpha (ER-alpha) is believed to be
      favorable in the prognosis and treatment of endometrial, ovarian, and breast
      cancer. High levels of ER-alpha have been shown to inhibit the growth and
      invasive, metastatic potential of breast cancer cell lines. To bring about these
      inhibitory effects, ER-alpha probably acts through other cellular factors
      involved in the regulation of cell growth. OBJECTIVE: To investigate the role of
      high levels ER-alpha in growth inhibition of endometrial cancer cells. METHODS: A
      human ER-alpha cDNA was stably overexpressed in an endometrial cancer cell line,
      namely, Ishikawa. ER-alpha-overexpressing, parent, and control Ishikawa cells
      were grown in vitro and their growth rates were compared by cell count. ER-alpha
      overexpressing and parent Ishikawa cells were also grown in vitro as tumors in a
      chicken chorioallantoic membrane (CAM) model, and tumor growth and angiogenesis
      was measured. Finally, levels of angiogenesis-modulating factors, nitric oxide
      synthase (NOS), and vascular endothelial growth factor (VEGF) were examined in
      relation to ER overexpression. RESULTS: The growth of Ishikawa cells was found
      inhibited in culture as well as in the CAM model. Angiogenesis of CAM tumors was
      also found inhibited in ER-overexpressing cells. Angiogenic factor VEGF was
      inhibited whereas the activity of NOS was found elevated following ER
      overexpression. CONCLUSION: Our work on the Ishikawa cell line indicates that
      high levels of ER-alpha in endometrial cancer may inhibit cancer growth by
      modulating angiogenic factors, thereby limiting the blood supply to the growing
      tumor. Our results support the earlier data from other groups that have shown a
      positive correlation between high ER content and better prognosis of endometrial
      cancers.

PMID- 15581977
TI  - Expression of p53, Ki-67, and CD31 in the vaginal margins of radical hysterectomy
      in patients with stage IB carcinoma of the cervix.
AB  - OBJECTIVES: This study was undertaken to evaluate the expression of p53, Ki-67,
      and CD31 both in the tumor and in the vaginal margins of radical hysterectomy in
      patients with stage IB squamous cell carcinoma of the cervix, as an attempt to
      use these proteins as possible markers for residual tumor in cervical cancer.
      METHODS: Thirty patients with stage IB squamous cell carcinoma of the cervix were
      submitted to radical hysterectomy (study group), and thirty patients with uterine
      myoma were submitted to vaginal hysterectomy (control group) and were
      prospectively studied from November 2001 to September 2002. Tissue samples were
      taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior
      vaginal margin (PVM) and were immunohistochemically evaluated by monoclonal
      antibodies for p53, Ki-67, and CD31. Vaginal samples in which the histological
      examination showed tumor involvement were excluded from the study. RESULTS:
      Patient's mean age was 48.7 +/- 10.4 years (27-73 years). The clinical stage was
      IB1 in 22 patients (73.3%) and IB2 in eight patients (26.7%). The expressions of
      p53, Ki-67, and CD31 were significantly higher in the tumor than in the benign
      cervix (P < 0.001). Higher expressions of these markers were noted in the vaginal
      margins of radical hysterectomy in patients with cervical carcinoma compared to
      the vaginal margins of control patients. This association was demonstrated for
      p53 in the AVM proximal (P = 0.045), for Ki-67 in AVM proximal (P < 0.001), AVM
      distal (P < 0.001), PVM proximal (P = 0.009), and PVM distal (P < 0.001), and for
      CD31 in AVM proximal (P = 0.003) and AVM distal (P = 0.018). There was no
      difference in p53, Ki-67, and CD31 expression between the proximal and distal
      regions of the vaginal margins in patients with carcinoma of the cervix.
      CONCLUSION: The expressions of p53, Ki-67, and CD31 were significantly higher in
      both the histologically positive (cervical tumor) and negative (vaginal margins)
      tissues of patients who had undergone radical hysterectomy for cervical cancer
      compared to the benign control tissues.

PMID- 15581978
TI  - Laparoscopically assisted radical vaginal hysterectomy vs. radical abdominal
      hysterectomy for cervical cancer: a match controlled study.
AB  - OBJECTIVES: The technical feasibility of laparoscopically assisted radical
      vaginal hysterectomy has been well described, but its advantages over the open
      technique remain largely unproven. We reviewed and compared our experiences with
      both approaches. METHODS: All patients undergoing laparoscopically assisted
      radical vaginal hysterectomy (LARVH) between 1996 and 2003 were identified and
      matched for age, FIGO stage, histological subtype and nodal metastases using a
      control group of women who underwent radical abdominal hysterectomy (RAH) during
      the same time period. RESULTS: Fifty-seven women were listed for LARVH, resulting
      in five conversions. Fifty cases were matched successfully using the criteria
      above. The majority of cases were FIGO stage 1B1. Statistically significant
      differences (P < 0.05) were present when the following were compared for LARVH
      vs. RAH: duration of surgery (median 180 vs. 120 min), blood loss (median 350 vs.
      875 ml), hospital stay (median 5 days vs. 8 days) and duration of continuous
      bladder catheterisation (median 3 days vs. 7 days). There were no statistically
      significant differences with regard to nodal yield, completeness of surgical
      margins or perioperative complication rate. Four major complications (8%, three
      cystotomies and one enterotomy) occurred in the LARVH group and three in the RAH
      group (6%, one pulmonary embolism, one ureteric injury and one major
      haemorrhage). Three women in LARVH group had seen a specialist regarding
      postoperative bladder dysfunction, versus 12 in the RAH group (P = 0.04). No
      patients in the LARVH group reported constipation requiring regular laxatives,
      versus six in the RAH group (P = 0.03). Median follow-up was 52 months for LARVH
      and 49 months for RAH. There was no significant difference between recurrence
      rates or overall survival (94% for LARVH vs. 96% for RAH). CONCLUSIONS: Despite
      the inherent limitations of LARVH and its associated learning curve, the
      procedure conveys many advantages over the open technique in terms of blood loss,
      transfusion requirement and hospital stay. In addition, the incidence of
      postoperative bladder and bowel dysfunction appears low-suggesting improved
      quality of life-without compromising survival.

PMID- 15581979
TI  - Allelic imbalances in endometrial stromal neoplasms: frequent genetic alterations
      in the nontumorous normal-appearing endometrial and myometrial tissues.
AB  - OBJECTIVES: Endometrial stromal sarcoma (ESS) is among the rarest primary
      malignant tumors of the uterus. The aim of this study was to examine the
      possibility of loss of heterozygosity (LOH) and microsatellite instability (MIS)
      in different tissue components of ESS. METHODS AND MATERIALS: Using PCR, we
      examined DNA extracts from microdissected tissues of 27 uterus samples containing
      malignant stromal cells of ESS (20 low grade and 3 high grade sarcomas), benign
      tumor cells of endometrial stromal nodules (ESN, 4 cases) as well as tumor-free
      myometrial and endometrial tissues close to and distant from the tumors. Normal
      cervical tissues (epithelial cells, stroma cells) were also microdissected and
      analyzed. Fifteen polymorphic DNA markers (chromosomes 2p, 3p, 5q, 10q, 11q, 13q,
      and 17p) were tested to identify possible genetic alterations. Samples from 10
      women with prolapsed uteri without any histopathologic abnormalities were also
      selected as controls. RESULTS: While no genetic alterations could be identified
      in 12 (44.5%) ESS cases, 15 (55.5%) revealed LOH with at least one polymorphic
      DNA marker. LOH were found in 3 (100%) high-grade sarcomas, 10 (50%) low-grade
      ESS, and 2 (50%) benign ESN. Although LOH was found more often in the neoplastic
      stromal cells, several cases showed concurrent and independent LOH in the tumor
      free myometrial or endometrial tissues either close to or distant from the
      tumors. The most common genetic abnormality (LOH) was observed at PTEN, a tumor
      suppressor gene located on chromosome 10q. No tumor was associated with
      microsatellite instability (MSI). The control group without any histologic
      abnormalities did not show LOH or MSI. CONCLUSIONS: The frequent occurrence of
      LOH and the lack of MSI suggest that loss of function(s) of tumor suppressor
      genes and not mismatch repair deficiency plays a key role in the pathogenesis of
      endometrial stromal neoplasms. The concurrent and independent occurrence of LOH
      in the stromal tumor cells and the tumor-free and normal-appearing myometrial and
      endometrial tissues strongly support the concept of genetic alterations in
      microenvironmental tissues and the interaction(s) between different tissue
      components in the development and progression of endometrial stromal neoplasms.

PMID- 15581980
TI  - Polymorphisms of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, and IL-18 and
      the risk of ovarian cancer.
AB  - OBJECTIVE: Recent studies of ovarian cancer have suggested a role for
      inflammation in carcinogenesis. Data from a population-based case-control study
      in Hawaii were examined to assess the relation between polymorphisms in cytokines
      involved with the inflammatory response, specifically members of the interleukin
      (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The
      analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the
      polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL
      18. Genotype data were obtained from blood samples collected in participants'
      homes, and reproductive, demographic, and lifestyle histories were collected
      during interview. RESULTS: There were no significant odds ratios (ORs) for
      ovarian cancer by allelic variants in any of the IL genes after adjusting for
      age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of
      tubal ligation. Although there was a significantly reduced risk of ovarian cancer
      risk among women with an IL-1alpha (-4845) T allele compared to women with two G
      alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age
      and ethnicity, the trend was not significant (p = 0.10). Further examination of
      the data suggested that women with at least one IL-18 variant allele (a G to C
      transition at position -137) were at significantly decreased risk of advanced
      ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women
      with the IL-18 GG genotype. There was a significant difference in the risk of
      ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04
      for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely
      to be diagnosed at regional/distant stages. Analysis of the data within ethnic
      subgroups revealed a significant positive association of the heterozygous IL-18
      GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95%
      CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native
      Hawaiian women homozygous for the IL-18 C allele, but only one case and control
      had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an
      association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms
      with the risk for ovarian cancer. However, the IL-18 G137C variant may be a
      marker for ovarian cancer progression or metastasis.

PMID- 15581981
TI  - Phase II study of carboplatin and whole body hyperthermia (WBH) in recurrent and
      metastatic cervical cancer.
AB  - OBJECTIVE: Hyperthermia enhances carboplatin cytotoxicity preclinically, and
      clinical studies have shown radiant heat Whole Body Hyperthermia (WBH) to be
      safe. In this study, the efficacy and toxicity of the combination of 41.8 degrees
      C WBH and carboplatin in recurrent and/or metastatic cervical cancer were
      explored. METHODS: Recurrent and/or metastatic cervical cancer patients were
      treated with 41.8 degrees C WBH and concurrent carboplatin, cycled every 28 days
      (max. 6 cycles). RESULTS: Twenty-one of 25 participants were evaluable for
      response: one complete remission, six partial responses, stable disease in nine
      patients and progression in five, leading to a response rate of 33%. Three of
      four evaluable chemotherapy pre-treated patients progressed, while this was seen
      in only 2 of 17 chemotherapy-naive patients. The median survival is 7.8 months
      (range 1.3 to 43+) and no patients were lost to follow up. Grades 3/4 toxicities
      were common: leukopenia in 35%, thrombopenia in 61% and anemia in 22% of all
      treatments. Excessive, partly reversible renal toxicity was seen in two patients
      (grades 3 and 4). CONCLUSION: The efficacy of WBH and carboplatin in recurrent
      and/or metastatic cervical cancer seems comparable to that of other palliative
      chemotherapy regimens in this disease. The considerable toxicity, though largely
      manageable, includes unexpected and severe unacceptable renal toxicity. This
      regimen seems less suitable for palliative care.

PMID- 15581982
TI  - Phase II study of weekly topotecan in patients with recurrent or persistent
      epithelial ovarian cancer.
AB  - OBJECTIVE: To assess the toxicity and effectiveness of once-weekly administration
      of topotecan (Hycamtin; GlaxoSmithKline) for relapsed ovarian and primary
      peritoneal cancer. METHODS: Twenty-three patients with recurrent or persistent
      epithelial ovarian cancer (EOC) and primary peritoneal carcinoma (PPC) previously
      exposed to at least one line of platinum-based chemotherapy were treated with IV
      weekly topotecan as a 30-min bolus at a starting dose of 4 mg/m(2) administered
      weekly for 3 weeks in a 28-day cycle. RESULTS: The patients' median age was 62
      years (42-83). Thirteen women (56.5%) were defined as having platinum-sensitive
      and 10 (43.5%) as having platinum-resistant disease. Altogether, 88 cycles were
      administered for a total of 264 weekly treatments, with a median of four courses
      (range 2-6). There were no treatment delays. The main bone marrow toxicity was
      grade II and III thrombocytopenia, necessitating dose reduction in four patients
      (17.4%) and treatment cessation in one patient. The most frequent nonhematologic
      toxicity was fatigue (nine patients, 39.1%). There were four complete responses
      (17.4%, three in the platinum-sensitive and one in the platinum-resistant
      patients) and seven (30.4%) partial responses, for an overall response rate of
      47.8%. The ORR was similar in platinum-sensitive and platinum-resistant patients
      (47.8% and 52.2%, respectively). The median progression-free survival was 4.9
      months with a mean survival time of 11.59 months. Two women sustained complete
      response lasting >6 months. CONCLUSION: Topotecan given as a weekly bolus is a
      highly active and well-tolerated treatment regimen for relapsed ovarian and
      primary peritoneal cancer and thus deserves further evaluation.

PMID- 15581983
TI  - Acetowhite epithelium.
AB  - OBJECTIVE: The study was undertaken to provide further understanding of the
      phenomenon of "acetowhite epithelium". METHODS: Solutions of acetic and similar
      acids were applied to the atypical transformation zone to demonstrate (or not)
      acetowhite epithelium. RESULTS: Acetowhite epithelium is not unique to acetic
      acid, but can be mimicked by other water soluble carboxylic acids. CONCLUSIONS:
      Acetowhite epithelium is probably due to the reflection of light from the
      superficial layers of epithelium when they become opaque following the rapid
      penetration of these non-coagulant fixatives and their effect on nucleoprotein.

PMID- 15581984
TI  - Treatment of ovarian germ cell tumors with a 3-day bleomycin, etoposide, and
      cisplatin regimen: a prospective multicenter study.
AB  - BACKGROUND: Ovarian germ cell tumors (OGCT) are highly curable when treated with
      cytoreductive surgery and platinum-based chemotherapy. We evaluated the safety
      and activity of a 3-day modified bleomycin, etoposide, and cisplatinum (mBEP)
      regimen in patients with OGCT. PATIENTS AND METHODS: Patients with FIGO stages I
      IV OGCT were treated with three (stages I-III complete resection) or four cycles
      (incomplete resection or stage IV) of bleomycin 15 mg iv, etoposide 120 mg/m(2)
      iv, and cisplatin 40 mg/m(2) iv for 3 days every 3 weeks. RESULTS: Forty-eight
      patients (14 with dysgerminoma and 34 with non-dysgerminomatous tumors) were
      included in our study. Most patients had stage I disease (65%) and complete
      resection of their tumor (67%). Twenty percent of patients developed grade 3 or 4
      neutropenia with 4 episodes of neutropenic fever. During follow-up (median: 5
      years), two patients developed progressive disease including one patient who
      died. All patients with stage I or II disease and all patients with dysgerminoma
      remain free of disease. However, 20% of patients with non-dysgerminomatous tumors
      stage III or IV experienced progressive disease. CONCLUSION: The modified 3-day
      BEP regimen was safe and effective in patients with OGCT. Further improvements
      are needed for patients with advanced, suboptimally debulked non-dysgerminomatous
      tumors.

PMID- 15581985
TI  - Patterns of recurrence and disease-free survival in advanced squamous cell
      carcinoma of the vulva.
AB  - OBJECTIVE: To compare patterns of recurrence and disease-free survival (DFS) of
      node-positive and node-negative patients with advanced vulval squamous cell
      carcinoma (SCC). METHODS: Fifty-five patients with FIGO stage III/IVA vulval SCC
      who had surgery at the Queensland Centre for Gynaecological Cancer from 1989 to
      1999 were included. Patients were grouped as follows: Group A, pT3 N0; Group B,
      pT3 N1; Group C, pT4 N2. Treatment included surgery +/- postoperative
      radiotherapy. Multivariate Cox models were calculated to identify independent
      prognostic factors. RESULTS: After a median follow-up of 96 months, 25 patients
      (45.5%) experienced recurrence at the vulva (n = 2), pelvis (n = 8), or distant
      sites (n = 15). Recurrence in the pelvis and at distant sites was more likely for
      patients in groups B and C (P 0.003). At 5 years the probability of DFS was
      66.6%, 35.3%, and 39.8% for patients in groups A, B, and C, respectively (P
      0.085). Patients with negative nodes (n = 15), one microscopic positive node (n =
      11), and two or more positive nodes (n = 29) had a probability of DFS of 66.6%,
      67.3%, and 26.1% at 5 years, respectively (P 0.005). CONCLUSION: Patients with >
      or =2 positive groin nodes are at risk for distant failure. The DFS of patients
      with negative groin nodes and those with only one microscopic positive node is
      very similar. The prognosis of patients with > or =2 positive unilateral or
      bilateral groin nodes is similar. The current FIGO staging system inaccurately
      reflects prognosis for patients with advanced vulval cancer. Clinical trials are
      warranted to investigate the benefit of systemic treatment.

PMID- 15581986
TI  - Adipose tissue concentrations of p,p'-DDE and the risk for endometrial cancer.
AB  - OBJECTIVE: To evaluate in a case-control study possible risk of endometrial
      cancer associated with environmental endocrine disruptors. METHODS: We analyzed
      the adipose tissue concentrations of polychlorinated biphenyls, hexachlorobenzene
      (HCB), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), chlordanes, and
      polybrominated biphenyls in 76 cases with endometrial cancer and 39 controls with
      benign endometrial hyperplasia. RESULTS: For the different chemicals, odds ratios
      (ORs) and 95% confidence intervals (CI) were close to unity taking the median
      concentration among the controls as cutoff value. However, for p,p'-DDE OR = 1.9,
      95% CI = 0.8-4.8 was obtained. Additional estrogen replacement therapy yielded in
      this category OR = 2.3, 95% CI = 0.6-8.6. CONCLUSION: The results suggest an
      interaction between p,p'-DDE and estrogen replacement drugs in the etiology of
      endometrial cancer, although no significant associations were found.

PMID- 15581987
TI  - Malignant mesenchymoma arising from a uterine leiomyoma in the menopause.
AB  - BACKGROUND: Malignant mesenchymoma is a rare tumor and location in the uterus is
      even rarer. We describe the first case of malignant mesenchymoma arising from a
      uterine fibroid in the menopause. CASE REPORT: A 64-year-old woman presented with
      abdominal pain and underwent surgery for a large "uterine fibroid" with
      suspicious features on ultrasound scan. The mass had developed after the
      menopause. Histology showed benign leiomyomatous tissue with malignant areas
      consistent with malignant mesenchymoma. CONCLUSION: We report the first case of
      malignant mesenchymoma arising from the uterus in menopause. Certain radiological
      features may be associated with this tumor. Due to its rarity, information on
      management of uterine malignant mesenchymoma is lacking and management options of
      uterine leiomyosarcomas are reviewed as a surrogate.

PMID- 15581988
TI  - Small cell carcinoma of the ovary with hypercalcemia causes severe pancreatitis
      and altered mental status.
AB  - BACKGROUND: Small cell carcinoma of the ovary is a rare, highly malignant tumor
      that often exhibits a paraneoplastic hypercalcemia. CASE: A 27-year-old female
      presented with pancreatitis and altered mental status with hypercalcemia. Further
      investigation revealed a left ovarian mass and a small cell carcinoma of the
      ovary, hypercalcemic type was found. Hysterectomy with bilateral salpingo
      oophorectomy was performed, and the patient underwent chemotherapy with
      carboplatin and paclitaxel. Hypercalcemia resolved after tumor resection. The
      patient has retroperitoneal lymph node recurrence at 16 months. CONCLUSION:
      Paraneoplastic hypercalcemia may result in pancreatitis and delirium. Small cell
      carcinoma of the ovary should be considered under these circumstances.

PMID- 15581989
TI  - Epstein-Barr virus positivity in primary vaginal lymphoma.
AB  - BACKGROUND: Primary non-Hodgkin lymphoma (NHL) of the vagina is a rare location.
      Its association with the Epstein-Barr virus (EBV) has been only reported in
      another case. We present a new case, emphasizing the oncogenetic relevance of
      EBV. CASE REPORT: A 45-year-old woman with a pelvic pain revealed in her vaginal
      inspection a thick and hard vaginal plug with a "paving stone" appearance. The
      biopsy reported a vaginal non-Hodgkin lymphoma type B of intermediate cell, with
      positive result for EBV. After treatment, a complete remission was obtained.
      CONCLUSION: The EBV is the main responsible for the non-Hodgkin lymphoma;
      classified as a group I carcinogen, it has been associated with a variety of
      neoplastic tumors, although it is unusual with extranodal type B diffuse
      lymphoma.

PMID- 15581990
TI  - Squamous cell carcinoma of the bladder presenting as vulvitis and cliteromegaly.
AB  - INTRODUCTION: Clitoral metastases are exceptionally rare. We present a case of a
      squamous cell carcinoma of the bladder presenting with a clitoral metastasis.
      CASE REPORT: We report the case of an 84-year-old lady with frequency, dysuria
      and a clitoral mass, which was found to be a poorly differentiated carcinoma on
      fine needle aspiration cytology. Cystoscopy revealed a moderate to poorly
      differentiated squamous cell carcinoma of the bladder. CONCLUSION: This is the
      first reported case of a squamous cell carcinoma of the bladder with clitoral
      metastasis. Clitoral metastases are exceptionally rare, with only seven previous
      cases reported in the literature. Although the commonest cause of cliteromegaly
      is hormonal, a metastatic carcinoma should be considered as part of the
      differential diagnosis in the elderly female.

PMID- 15581991
TI  - Aggressive angiomyxoma of the vulva.
AB  - BACKGROUND: Aggressive angiomyxoma is a rare soft tissue tumour that carries a
      high risk of local relapse. It is a slowly growing and locally infiltrating
      tumour. CASE: We describe the case of an aggressive pelvic-perineal angiomyxoma
      arising in a 36-year-old woman. The patient had a mass that grew before, during
      and after her pregnancy. Transperineal surgery was performed. The resection
      margins were free of disease. CONCLUSION: Our case confirms what has previously
      been published concerning the possible hormone-dependence of this neoplasm. Given
      the positive estrogen and progesterone receptor status of this tumour, we will
      consider hormonal treatments in the case of a future relapse.

PMID- 15581992
TI  - Endometrial carcinoma in one horn of a bicornuate uterus.
AB  - BACKGROUND: Tamoxifen therapy is related to endometrial adenocarcinoma.
      Bicornuate uteri are more common than assumed. There are a few reports of
      endometrioid carcinoma arising in a bicornuate uterus, but none of these discuss
      a serous papillary component or an association with tamoxifen therapy. CASE: This
      is a case of a mixed endometrioid and serous papillary endometrial carcinoma
      arising in one horn of a bicornuate uterus. Multiple benign polyps were also
      present. CONCLUSION: Adequate tissue sampling of both horns is critical to
      arriving at a timely and accurate diagnosis of malignancy in patients with a
      bicornuate uterus.

PMID- 15581993
TI  - Bilateral primary ovarian leiomyoma in a young woman: case report and literature
      review.
AB  - BACKGROUND: Primary ovarian leiomyoma is a very rare tumor and usually it is
      small, unilateral-, and concomitantly seen with uterine leiomyomata in middle
      aged to postmenopausal women. CASE: We describe a case of huge, bilateral ovarian
      leiomyoma that was not associated with uterine tumor in a 17-year-old woman. The
      authors of this study documented the smooth muscle origin of the tumor with
      immunohistochemical studies, the available literature was reviewed and the
      possible histogenesis was discussed. CONCLUSION: We herein report a case of a
      rare primary bilateral ovarian leiomyoma in a young woman.

PMID- 15581994
TI  - Bilateral peripheral T-cell lymphoma of the fallopian tubes.
AB  - BACKGROUND: Lymphoma of the female genital tract is rare, and usually involves
      the ovaries or the uterus. Most cases of fallopian tube lymphoma reflect disease
      arising in the ovaries. All previously reported cases of primary lymphoma of the
      fallopian tube were of B cell lineage. CASE: A 51-year-old woman presented with
      systemic upset and a pelvic mass. At laparotomy, both fallopian tubes were
      inflamed and histological examination revealed peripheral T-cell lymphoma. At
      staging, she had IIB(E) disease, and she was treated with six cycles of CHOP-M
      chemotherapy. CONCLUSION: Our case is unusual in that this is the first described
      case of peripheral T-cell lymphoma arising in the fallopian tubes and is moreover
      unusual because of the involvement of both fallopian tubes without involvement of
      other gynaecological organs. The clinical course was favourable with complete
      remission maintained for more than 5 years.

PMID- 15581995
TI  - Management of upper gastrointestinal obstruction in advanced ovarian cancer with
      intraluminal stents.
AB  - BACKGROUND: The course of many patients with end-stage gynecologic malignancy
      will be complicated by malignant bowel obstruction. Intraluminal stents are a
      novel alternative to standard surgical intervention which can involve
      considerable patient risk. CASES: Two cases are presented of patients with upper
      gastrointestinal obstruction due to recurrent ovarian cancer. In the first case,
      a stent was utilised to provide relief from nocturnal vomiting secondary to
      duodenal obstruction. In the second case, stent insertion for subtotal gastric
      outlet obstruction provided initial relief from vomiting. However, recurrence of
      symptoms occurred due to stent occlusion from tumour ingrowth. CONCLUSIONS: In
      patients with upper gastrointestinal obstruction due to recurrent gynecologic
      malignancy, intraluminal stents can provide useful palliation.

PMID- 15581996
TI  - Leiomyomatosis peritonealis disseminata with malignant change in a post
      menopausal woman.
AB  - BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition
      characterized by multiple subperitoneal nodules of benign smooth muscle. The
      lesion usually occurs in women of childbearing age. CASE: A 55-year-old woman
      with a history of panhysterectomy 8 years ago presented with an abdominal lump.
      Ultrasonographic and peroperative finding of multiple omental nodules led to a
      clinical impression of disseminated malignancy. Only the largest nodule was
      excised, histopathology of which revealed a cellular leiomyoma. Seven months
      later, she developed an omental leiomyosarcoma. An omentectomy was done and the
      multiple smaller nodules were all confirmed to be composed of benign
      leiomyocytes. CONCLUSION: Malignant transformation in LPD in post-menopausal
      patients is an exceptional event that has been documented only twice previously
      in English literature.

PMID- 15581997
TI  - Recurrent immature teratoma of the ovary: a case report of radical secondary
      cytoreduction with replacement of the aortic bifurcation.
AB  - BACKGROUND: Composing of less than 1% of all ovarian cancers, immature teratoma
      is a malignancy that mainly affects the young. Although standard treatment
      protocol for primary disease has improved over the past decades, the role of
      secondary cytoreduction in the setting of recurrence remains controversial. CASE:
      A 20-year-old Chinese female presented with recurrent immature teratoma at the
      level of the aortic bifurcation. Patient was status post a right salpingo
      oophorectomy at time of her initial diagnosis 8 years ago, and subsequent
      exploratory laparotomies and chemotherapy when recurrence that developed at the
      before-mentioned site. She ultimately underwent a radical cytoreduction with en
      block excision of the aortic mass and simultaneous artificial aortic bifurcation
      graft. CONCLUSION: There may be a beneficial role of radical secondary
      cytoreduction in the setting of recurrent immature teratoma.

PMID- 15581998
TI  - Non-Hodgkin malignant lymphoma revealed by an ovarian tumor case report and
      review of the literature.
AB  - BACKGROUND: The initial manifestation of a lymphoma as an ovarian mass is
      unusual, with a reportedly poor prognosis. An exploratory laparotomy is often
      performed as the ovarian tumor can mimic an advanced epithelial carcinoma. The
      criteria of lymphoma used in the selection of a nonsurgical approach, that is,
      chemotherapy possibly associated with radiation, are rarely defined. CASE: We
      report the case of a 36-year-old woman who presented with an ovarian tumor
      suggestive of advanced carcinoma. After an initial approach including optimal
      surgery, the diagnosis of large B-cell CD30+ non-Hodgkin malignant lymphoma was
      established. Complete remission was obtained after a chemotherapy regimen,
      appropriate to the specific histologic type of the lymphoma. CONCLUSION: The
      choice treatment of ovarian non-Hodgkin lymphoma (NHL) is chemotherapy. In the
      presence of an ovarian tumor, the possibility of ovarian NHL must be considered,
      and its clinical, biological, and/or radiological signs must be actively sought.
      Controlled biopsies must also be included to avoid mutilating surgery.

PMID- 15581999
TI  - Microinvasive Paget's disease.
AB  - BACKGROUND: Microinvasive squamous cell carcinoma of the vulva is defined as
      stromal invasion < or =1 mm and is treated by wide local resection. Whether
      criteria for microinvasive squamous cell carcinoma can be applied to Paget's
      disease of the vulva is unknown because of the rarity of that disease. CASES: We
      initially evaluated three cases of microinvasive Paget's disease by using
      sentinel lymph node (SLN) analysis. The SLNs in two patients were negative; and
      these patients had no recurrence of invasive or metastatic Paget's disease. The
      other patient had a positive SLN (the only positive lymph node) and subsequently
      received complete lymph node dissection of the groin bilaterally. CONCLUSION:
      Evaluation of SLNs may be valid for evaluating microinvasive Paget's disease.

PMID- 15582000
TI  - Primary vaginal adenosarcoma with sarcomatous overgrowth.
AB  - BACKGROUND: Primary vaginal adenosarcomas are extremely rare, and typical
      adenosarcomas are of low malignancy. However, aggressive forms with sarcomatous
      overgrowth have been reported, those appear to have a poor prognosis. CASE: A 52
      year-old woman who had undergone prior surgery for uterine leiomyoma and an
      ovarian cyst (total abdominal hysterectomy and left salpingo-oophorectomy)
      presented 10 years later with a rapidly enlarging tumor arising from the vaginal
      cuff. Repetitive biopsy samples revealed a mixture of benign epithelial gland and
      malignant stromal components with periglandular stromal hypercellularity and
      sarcomatous overgrowth. A histological diagnosis of mullerian adenocarcinoma was
      made. The patient died from recurrent disease 9 months after surgery. CONCLUSION:
      Regardless of primary focus, adenosarcoma with sarcomatous overgrowth is
      associated with postoperative recurrence and a fatal outcome.

PMID- 15582001
TI  - Levonorgestrel-releasing intrauterine system (LNG-IUS) as a therapy for
      endometrial carcinoma.
AB  - BACKGROUND: Primary treatment of endometrial cancer with progestogens is reserved
      for adjuvant or palliative treatment, although with unproven efficacy. CASE: We
      present a case of early endometrial cancer where a combination of oral
      progestogens and levonorgestrel releasing intrauterine system (Mirena) was used
      as a primary treatment, as the standard surgical treatment was deemed to carry an
      unacceptable mortality risk. CONCLUSION: Our treatment has resulted in reversion
      of the cancerous endometrial histological changes. This is encouraging, but
      obviously more cases and lengthier follow-up time are required in order to obtain
      more valid conclusions.

PMID- 15582002
TI  - Interest of F-18 fluorodeoxyglucose positron emission tomography in the
      evaluation of vaginal malignant melanoma.
AB  - BACKGROUND: This is the first report of FDG-PET findings in a case of vaginal
      melanoma. CASE: The tumor arose from the anterior wall of the vaginal canal. As
      the tumor was limited to the vaginal wall and as there was no evidence of distant
      metastases, the disease was staged as IIC (AJCC 2002). PET-CT images showed two
      mediastinal foci localized to the left highest mediastinal and subcarinal nodes
      on fusion PET/CT images. As it was metastatic, the disease was staged IV (AJCC
      2002). CONCLUSION: In comparison to conventional imaging, FDG-PET provides a more
      accurate assessment of the extent of disease spread in patients with vaginal
      melanoma as with cutaneous melanoma. Significant alterations in the surgical
      management and treatment were made based on PET results.

PMID- 15582003
TI  - Low-grade endometrial stromal sarcoma treated with the aromatase inhibitor
      letrozole.
AB  - BACKGROUND: Low-grade endometrial stromal sarcoma is an indolent steroid
      responsive tumor. Successful hormonal treatment, most commonly with megestrol
      acetate, has been reported. CASE: A 76-year-old woman underwent a total abdominal
      hysterectomy with bilateral salpingo-oophorectomy 25 years earlier allegedly for
      a benign condition. She presented to us with postrenal kidney failure and a huge
      pelvic mass compressing both ureters. After transvaginal trough-cut biopsy of the
      mass, the diagnosis of low-grade endometrial stromal sarcoma with a high
      expression of alpha-estrogen receptor was made. The patient was treated with
      letrozole only with a spectacular response. CONCLUSION: To the best of our
      knowledge, this is the first case for which letrozole was used on long-term basis
      as first-line hormonal treatment for a recurrent low-grade stromal sarcoma.

PMID- 15582004
TI  - Endometrial adenocarcinoma: an apostasy from early views.

PMID- 15582005
TI  - Comment on "Malignant mixed Mullerian tumor of the ovary: an argument for BRCA3
      or a coincidental cluster of unconnected cancer".

PMID- 15582006
TI  - Survival following the documentation of platinum and taxane resistance in ovarian
      cancer.

PMID- 15582010
TI  - Comment on "The impact of complete surgical staging on adjuvant treatment
      decisions in endometrial cancer".

PMID- 15582011
TI  - Effect of 5-HT1B/D receptor agonist and antagonist administration on motor
      function in haloperidol and MPTP-treated common marmosets.
AB  - An interaction between brain serotonergic and dopaminergic systems involving 5
      HT(1B) receptors may contribute to motor complications arising from the drug
      treatment of neurological and psychiatric disorders. This study assessed the
      effects of treatment with a non-selective 5-HT(1B/D) receptor agonist and a
      selective 5-HT(1B) receptor antagonist on akinesia induced in marmosets by long
      term treatment with haloperidol and on motor disability and l-3, 4
      dihydroxyphenylalanine (L-DOPA)-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-treated marmosets. In marmosets treated chronically
      with haloperidol, the 5-HT(1B) agonist SKF-99101-H reduced locomotor activity and
      induced motor disability, whereas the 5-HT(1B) antagonist SB-224289-A had no
      effect on motor behaviour. Haloperidol administration induced a suppression of
      locomotor activity which was not reversed by co-administration of either SKF
      99101-H or SB-224289-A. In MPTP-treated common marmosets, neither SKF-99101-H nor
      SB-224289-A induced any significant change in motor function. However, SKF-99101
      H inhibited L-DOPA-induced dyskinesia and the reversal of motor deficits whereas
      SB-224289-A was without effect. The results of this study indicate that the 5
      HT(1B) receptor appears not to be an appropriate target for the treatment of
      Parkinson's disease (PD) or for the control of drug-induced motor complications
      developed as a tong-term consequence of neuroleptic or L-DOPA treatment.

PMID- 15582012
TI  - Improved cognitive performance in human volunteers following administration of
      guarana (Paullinia cupana) extract: comparison and interaction with Panax
      ginseng.
AB  - Extracts from the plant guarana (Paullinia cupana) feature as putatively
      stimulating ingredients in a number of foods, drinks and dietary/herbal
      supplements. To date, little research in humans has examined the potential
      psychoactive effects of these extracts. Extracts of Panax ginseng, which are
      often sold in combination with guarana, contain similar potentially active
      components, and have been shown to modulate cognitive performance. In this double
      blind, counterbalanced, placebo-controlled study, the cognitive and mood effects
      of separate single doses of: 75 mg of a dried ethanolic extract of guarana
      (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75
      mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day
      of the study (separated by a 7-day washout), cognitive performance and subjective
      mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the
      Cognitive Drug Research computerised assessment battery, Serial subtraction tasks
      and Bond-Lader mood scales. In comparison to placebo, all three treatments
      resulted in improved task performance throughout the day. In the case of guarana,
      improvements were seen across 'attention' tasks (but with some evidence of
      reduced accuracy), and on a sentence verification task. While also increasing the
      speed of attention task performance, both ginseng and the ginseng/guarana
      combination also enhanced the speed of memory task performance, with little
      evidence of modulated accuracy. Guarana and the combination, and to a lesser
      extent ginseng, also led to significant improvements in serial subtraction task
      performance. These results provide the first demonstration in humans of the
      psychoactive effects of guarana, and confirmation of the psychoactive properties
      of ginseng. Given the low caffeine content (9 mg) of this dose of guarana
      extract, the effects are unlikely to be attributable to its caffeine content.

PMID- 15582013
TI  - Recovery of experimental Parkinson's disease with the melatonin analogues ML-23
      and S-20928 in a chronic, bilateral 6-OHDA model: a new mechanism involving
      antagonism of the melatonin receptor.
AB  - Over the past 10 years, there has been a resurgence of interest in examining the
      role of melatonin in health and disease. While the brunt of research in this area
      has portrayed melatonin in a favorable light, there is a growing body of evidence
      suggesting that melatonin may possess adverse effects contributing to the
      development of various neuropsychiatric disease states. In preclinical models of
      Parkinson's disease (PD), melatonin has been shown to enhance the severity of
      this condition while its antagonism, using constant light or pinealectomy,
      facilitates recovery. To test this hypothesis further, the present study employed
      the melatonin analogues ML-23 and S-20928 in a post-6-OHDA injection regime to
      determine whether they may have a favorable effect on the symptoms of this more
      chronic model of PD. When ML-23 was injected I.P. in a dose of 3 mg/kg twice
      daily for 3.5 days after 6-OHDA, significant improvement in motor function and
      regulatory deficits was observed. Similarly, the injection of S-20928 in a 1
      mg/kg dose (I.P.), in the same regimen, facilitated modest improvement in motor
      function and regulatory deficits while the larger dose enhanced the severity of
      behavioural deficits and produced severe side effects causing deterioration in
      condition during the course of drug administration. ML-23 administration totally
      abolished the 6-OHDA-induced mortality, which accompanies dopamine (DA)
      degeneration, while S-20928 had no effect on this parameter. These results
      suggest that some melatonin analogues can aid in recovery from DA depleting
      lesions after DA degeneration has commenced and the recovery is not attributable
      to the antioxidative properties of this hormone. While the exact mechanism by
      which ML-23 and S-20928 are exerting their therapeutic effect is unclear, it is
      possible that antagonism of melatonin receptors may play some role and this
      should be considered when assessing the potential of melatonin analogues for
      treatment of human neuropsychiatric disorders.

PMID- 15582014
TI  - Increasing the selectivity of the discriminative stimulus effects of delta 9
      tetrahydrocannabinol: complete substitution with methanandamide.
AB  - In an attempt to increase the selectivity of the discriminative stimulus effects
      of Delta9-tetrahydrocannabinol (THC), rats were trained to discriminate 3.2 mg/kg
      of this compound from a group of "other" drugs consisting of morphine (3.2
      mg/kg), PCP (2.5 mg/kg), and vehicle. Acquisition of the Delta9-THC-other
      discrimination was rapid (38 days) and did not differ significantly from that of
      a group of "control" animals trained to discriminate Delta9-THC (3.2 mg/kg) from
      its vehicle (33 days). In substitution (generalization) tests, a high dose of
      anandamide, which also severely decreased response rate, substituted partially in
      both the control and the Delta9-THC-other group; (R)-methanandamide, an analog of
      anandamide which is metabolized more slowly, substituted completely for Delta9
      THC in the control, and partially in the Delta9-THC-other group; neither
      pentobarbital nor diazepam substituted completely for Delta9-THC under any
      experimental condition. Regardless of the level of Delta9-THC lever responding,
      all drugs except diazepam substituted less in the Delta9-THC-other than in the
      control group. For this reason, the Delta9-THC-other training procedure might be
      described as being more selective than the commonly used drug-no drug procedure.

PMID- 15582015
TI  - Recent advances in animal models of alcohol craving and relapse.
AB  - Animal models designed to examine different facets of alcohol-related behaviors
      have been developed to study genetic and neurobiological factors underlying
      alcoholism and alcohol abuse. One goal has been to develop valid, congruent,
      complementary animal models of alcohol craving and relapse, with the ultimate
      objective of assessing the effectiveness of pharmacological agents with these
      models. Animal models of alcohol craving include drug-induced responding (drug
      reinstatement), cue-induced responding, Pavlovian Spontaneous Recovery (PSR), and
      appetitive/consummatory responding. A primary experimental approach to study
      alcohol relapse has been through expression of the Alcohol Deprivation Effect
      (ADE) following a single deprivation or multiple deprivations. To date, five
      selectively bred lines of rats have been developed to study alcohol-drinking
      behavior. These are the ALKO/Alcohol (AA), alcohol-preferring (P), high alcohol
      drinking (HAD-1 and HAD-2 replicates), and the Sardinian alcohol-preferring (sP)
      lines of rats. Findings thus far indicate that only the P line of rats meets all
      the criteria established for a valid animal model of alcoholism, with progress
      having been made in characterizing the AA, HAD and sP lines of rats. The focus of
      the current review will be to analyze the various models of alcohol craving,
      emphasizing the use of the Indiana University selected rat lines (P and HADs).
      Overall, the findings indicate substantial progress has been made in developing
      animal models of alcohol abuse, relapse and craving using these selectively bred
      rat lines, as well as outbred rats.

PMID- 15582016
TI  - Chronic cocaine pretreatment facilitates Pavlovian sexual conditioning in male
      Japanese quail.
AB  - Repeated drug exposure that results in behavioral sensitization has been shown to
      enhance sex-seeking behaviors in rats as well as facilitate Pavlovian excitatory
      and inhibitory conditioning. In the present experiment, male Japanese quail were
      given repeated presentations of cocaine (10 mg/kg, i.p.) that resulted in
      increased locomotor activity relative to saline. After a 10-day withdrawal
      period, subjects received sexual conditioning trials that consisted of
      presentation of an object conditioned stimulus (CS) followed by sexual
      reinforcement. Results showed that birds that previously received chronic cocaine
      demonstrated more conditioned approach behavior to the CS object, a shorter
      latency to copulate with a female, and made more cloacal contacts (copulatory
      behavior) during sexual reinforcement than saline-treated birds. The findings
      suggest that chronic cocaine later facilitates Pavlovian conditioning in a sexual
      behavior paradigm. This may be the result of cocaine facilitating learning via
      the dopaminergic system. The findings are discussed in the context of the
      incentive sensitization theory and possible neuronal mechanisms.

PMID- 15582017
TI  - Effects of MDMA administration on scopolamine-induced disruptions of learning and
      performance in rats.
AB  - Functional deficits following short-course high-dose administration of 3,4
      methylenedioxymethamphetamine (MDMA) have been difficult to characterize despite
      evidence indicating that MDMA is neurotoxic in several species. Therefore, the
      present research used rats trained to respond under a complex behavioral
      procedure (i.e., a multiple schedule of repeated acquisition and performance of
      response chains), pharmacological challenge with scopolamine and neurotransmitter
      assays to examine the effects of MDMA neurotoxicity on learning. Prior to MDMA
      administration, 0.032-0.32 mg/kg of scopolamine produced dose-dependent rate
      decreasing and error-increasing effects in both components of the multiple
      schedule. Administration of 10 mg/kg of MDMA twice per day for 4 days also
      produced rate-decreasing and error-increasing effects on these days, but
      responding returned to baseline levels several days after the final injection. In
      contrast to the recovery of responding, this regimen of MDMA in untrained rats
      significantly reduced levels of both serotonin and its major metabolite, 5
      hydroxyindoleacetic acid (5-HIAA), for 13-14 days. Furthermore, the rate
      decreasing and error-increasing effects of scopolamine were significantly
      attenuated after MDMA treatment. These results indicate that certain complex
      operant behaviors rapidly recover from the effects of short-course high-dose MDMA
      administration, despite the reduced levels of serotonin in the central nervous
      system (CNS), and that this MDMA-induced loss of serotonin may affect cholinergic
      transmission.

PMID- 15582018
TI  - Mechanisms of the anti-inflammatory activity of the leaf extracts of Culcasia
      scandens P. Beauv (Araceae).
AB  - The mechanisms of the anti-inflammatory activity of the leaf extracts of Culcasia
      scandens P. Beauv were evaluated. The methanol leaf extract (CE) of C. scandens
      was subjected to bioactivity-guided separation to obtain fraction C as the most
      active anti-inflammatory fraction. Further activity-guided fractionation of
      fraction C led to the isolation of an anti-inflammatory principle, CS-1,
      identified as sitosterol. Phytochemical analysis of CE indicated the presence of
      carbohydrates, glycosides, alkaloids, saponins, flavonoids, tannins, sterols and
      terpenoids. Fraction C tested positive for flavonoids, sterols and terpenoids
      while CS-1 tested positive for sterols. Acute toxicity test on CE in mice
      established an intraperitoneal (i.p.) and oral (p.o.) LD50 of >5 g/kg. The
      isolated compound, CS-1, inhibited topical edema in the mouse ear while CE and
      fraction C were devoid of any such activity. The methanol extract (CE), fraction
      C and CS-1 suppressed paw edema in rats with inhibitory order of magnitude: CS
      1>fraction C>CE. The methanol extract (CE), fraction C and CS-1 caused
      gastrointestinal irritation in rats to varying extents and reduced neutrophil and
      lymphocyte counts while CE and fraction C reduced total leukocyte count (TLC).
      The methanol extract (CE) was effective in inhibiting heat-induced hemolysis of
      human red blood cells (RBCs) but exhibited no inhibitory effect on hypotonicity
      induced hemolysis. However, fraction C and CS-1 inhibited both heat- and
      hypotonicity-induced hemolysis. These results suggest that the leaf extract of C.
      scandens has a good anti-inflammatory profile, indicating a nonspecific mechanism
      of action.

PMID- 15582019
TI  - Effects of morphine on brain-stimulation reward thresholds in young and aged
      rats.
AB  - Mesolimbic opioid systems are altered with aging; however, the effects of these
      changes on the rewarding actions of opioids have not been examined. The present
      experiment assessed differences in the responsiveness of brain reward pathways in
      young and aged rats to the effects of morphine using the brain-stimulation reward
      (BSR) model. Aged (24 months) and young (5 months) male F344/BNF1 rats were
      stereotaxically implanted with a bipolar stainless steel electrode into the
      lateral hypothalamic (LH) region of the medial forebrain bundle. Thresholds were
      determined using the rate-independent psychophysical method. Each animal was
      tested after the administration of saline or morphine at 0.5, 1, 2.5, 5 and 10
      mg/kg doses. A significant difference in the mean baseline threshold between aged
      (99.8+/-6 microA) and young rats (149.1+/-14 microA) was observed. Although in
      both groups morphine lowered the BSR threshold, there were no significant
      differences between the groups except at the 10-mg/kg dose, the difference did
      approach significance. This study indicates that there are baseline differences
      in the rewarding threshold in the two groups, that morphine lowers the threshold
      in young and aged animals and that the hedonic effects produced by morphine, for
      the most, part remain preserved in aged animals.

PMID- 15582020
TI  - Increased sensitization to morphine-induced oral stereotypy in aged rats.
AB  - Sensitization develops to the stereotypic biting behavior that appears with the
      repeated administration of high dose morphine to rats. Because there is evidence
      that this behavior is dopamine-mediated and that there are age-related changes in
      dopamine systems, we compared the development and expression of morphine-induced
      biting behavior in aged (24 months) and young rats (5 months). Animals were
      treated with four sensitizing 10 mg/kg doses of morphine or saline, followed by
      three weekly challenges with 4 mg/kg doses of morphine or saline. By the fourth
      sensitizing morphine dose and after the administration of each low dose
      challenge, the biting time was significantly greater for aged than for young
      morphine pre-treated rats. After the first weekly low dose challenge, the aged
      but not young animals expressed more biting than when they did after the last 10
      mg/kg dose. These results indicate that sensitization to morphine-induced oral
      stereotypy is significantly greater in aged as compared to young rats. Age
      related enhanced sensitivity to morphine-induced oral stereotypy might be related
      to age-induced increases in vulnerability to opioid-induced insults to the basal
      ganglia, and may be a model for certain diseases of this pathway.

PMID- 15582021
TI  - The effect of venlafaxine on behaviour, body weight and striatal monoamine levels
      on sleep-deprived female rats.
AB  - Partial sleep deprivation is clinically associated with fatigue, depressive
      symptoms and reduced memory. Previously, it has been demonstrated that
      venlafaxine, an atypical antidepressant, increases the levels of noradrenaline
      and serotonin in rat hippocampus. The aim of this study was to evaluate the
      effects of venlafaxine on depression, anxiety, locomotor activity and memory in a
      model of REM sleep (REMs) deprivation in rats. We have also studied the influence
      of venlafaxine on monoamine levels in the striatum. Six groups of animals (N=20
      each) were treated with saline or venlafaxine (1 or 10 mg/kg) during 10 days,
      submitted or not to REMs deprivation and studied with the forced swimming test of
      Porsolt (STP), plus-maze, passive avoidance and open-field tests right after
      sleep deprivation. Animals were also studied for passive avoidance 24 h later
      (rebound period). Brain samples for monoamine measurements were collected either
      immediately after REMs deprivation or after 24 h. Both REMs deprivation and
      venlafaxine showed an antidepressant effect. An anxiolytic effect was also
      observed after REMs deprivation. Previous treatment with venlafaxine blocked the
      antidepressant and anxiolytic effects of REMs deprivation. REMs deprivation alone
      and treatment with venlafaxine 10 mg/kg increased locomotor activity, and this
      effect was inhibited by venlafaxine in REMs deprived rats. Both venlafaxine
      treatment and REMs deprivation induced weight loss. Venlafaxine treatment, but
      not REMs deprivation, induced an increase in striatal dopamine (DA) levels. The
      combination of REMs deprivation and venlafaxine treatment was associated with an
      increase in serotonin turnover 24 h after rebound sleep. In this study,
      venlafaxine treatment hindered most behavioral effects of REMs deprivation and
      was associated with an interference on dopamine and serotonin systems in the
      striatum.

PMID- 15582022
TI  - Reinstatement of nicotine self-administration in rats by presentation of nicotine
      paired stimuli, but not nicotine priming.
AB  - The objective of the present study was to determine the relative efficacy of
      nicotine priming and nicotine-paired stimuli in reinstating extinguished NSA in
      rats. The relative efficacy of different stimulus conditions in reinstating NSA
      was also determined. Rats were trained to self-administer nicotine (0.03
      mg/kg/inf) under an FR 5 schedule. Onset of a light above the active lever was
      correlated with nicotine availability, while offset of the light was paired with
      each nicotine infusion. In Experiment 1, saline extinction was arranged in the
      presence of these light stimuli. After extinction criteria were met, the effects
      of priming doses of nicotine (0.01, 0.03. and 0.06 mg/kg/inf, i.v.) on active
      lever pressing were determined. In Experiment 2, extinction of NSA was arranged
      in the absence of the light stimuli. After extinction criteria were met,
      reinstatement sessions were arranged involving either (1) a priming infusion of
      nicotine (0.03 mg/kg), (2) presentation of the same light stimuli as during NSA
      training, (3) constant illumination of the cue light, or (4) a combination of a
      nicotine priming infusion with one of the stimulus-light conditions. In
      Experiment 1, nicotine generally failed to reinstate NSA at any priming dose. In
      Experiment 2, both stimulus conditions reinstated NSA, with the stimulus
      condition identical to training producing a greater effect. Nicotine priming
      alone failed to significantly reinstate NSA. Nicotine priming combined with
      either stimulus condition was no more effective than each stimulus condition
      alone in reinstating NSA. These findings suggest that nicotine-paired cues are
      more effective than nicotine alone in reinstating extinguished NSA and are
      consistent with other studies showing that nicotine-paired stimuli play an
      important role in the reacquisition of NSA.

PMID- 15582023
TI  - Effects of morphine or naloxone on cocaine-induced genital reflexes in
      paradoxical sleep-deprived rats.
AB  - The involvement of opioidergic neurotransmission in the modulation of genital
      reflexes induced by paradoxical sleep deprivation (PSD) and cocaine in rats was
      the aim of the present study. Morphine (0, 1, 5 and 10 mg/kg) and naloxone (0,
      0.3, 3 and 30 mg/kg) were administered prior to saline or cocaine to rats that
      had been deprived of sleep and the incidence of penile erections (PE) and
      ejaculations (EJ) was measured. PSD alone induced PE in 50% and EJ in 20% of the
      rats, but these behaviors were not influenced by morphine or naloxone. Cocaine
      potentiated the incidence of genital reflexes in PSD rats to 90% (PE) and 70%
      (EJ). Morphine and not naloxone significantly reduced the percentage of rats
      displaying this response at the highest doses. Morphine also significantly
      reduced PE and EJ frequencies at 10 mg/kg. Furthermore, this inhibitory effect of
      morphine on genital reflexes was prevented by the prior injection of naloxone.
      Although a number of factors are involved in such a complex phenomenon as PE and
      EJ, our data show that activation of the opioidergic systems by the agonist
      morphine reduces genital reflexes-induced by cocaine in PSD males while the
      antagonist, naloxone, did not have any significant effect. The findings suggest
      that the stimulating effects of cocaine in potentiating genital reflexes in PSD
      rats can be unidirectionally modified by opioidergic systems.

PMID- 15582024
TI  - Evidence for zolpidem-induced hyperphagia, but not anxiolysis, in a successive
      negative contrast paradigm.
AB  - Zolpidem is an imidazopyridine which binds to certain benzodiazepine receptor
      types with varying degrees of affinity. The effect of zolpidem on successive
      negative contrast was investigated in three experiments. In each experiment, a
      contrast group was given brief access to 32% sucrose for 10 days, then shifted to
      4% sucrose for 2 days; a procedure that elicits anxiety primarily on the second
      postshift day. One control group was given only 4% sucrose. Experiments 2 and 3
      included a 2% sucrose group as an intake rate-dependent control. In Experiment 1,
      zolpidem (4.0 and 0.5 mg/kg) dose-dependently reduced contrast on the two
      postshift days. Contrast occurred during the first postshift consummatory burst.
      Zolpidem prolonged the first postshift burst equally in both shifted and
      unshifted groups, suggesting a general facilitation of intake masked by a ceiling
      effect in controls. In Experiment 2, zolpidem's (4.0 mg/kg) anti-contrast action
      was equivalent to its hyperphagic effect in the 2% control group. Zolpidem
      prolonged the first postshift burst equally in all three groups, again consistent
      with general intake facilitation. In Experiment 3, 8.0 mg/kg zolpidem produced an
      anti-contrast effect not present in 2% controls on both postshift days. This does
      not appear attributable to anxiolysis, however, as the effect was equivalent
      during stressful and non-stressful phases of the postshift period, and zolpidem
      extended the duration of the first postshift burst equally in all three sucrose
      groups. Thus, unlike benzodiazepines, zolpidem is not anxiolytic in this
      paradigm.

PMID- 15582025
TI  - Behavioral changes after acetylcholinesterase inhibition with physostigmine in
      mice.
AB  - The effect of the central and peripheral acetylcholinesterase (AChE) inhibitor,
      physostigmine (PHY), was examined on spatial memory using a water maze, motor
      activity as well as acoustic startle response (ASR) and prepulse inhibition (PPI)
      in C57BL/6J mice. PHY was administered intraperitoneally (IP) at doses of 0.0,
      0.01, 0.03, 0.1 and 0.3 mg/kg and the mice were tested 30 min after injection.
      Administration of PHY reduced motor activity in the open field in a dose
      dependent fashion, with notable decreases in activity observed at 0.1 and 0.3
      mg/kg. The results also showed that animals receiving 0.1 mg/kg spent more total
      time in the peripheral zone than in the central zone. The water maze data showed
      impairment of acquisition and performance of the task, accompanied by a reduced
      swimming time and enhanced thigmotaxis at a dose of 0.1 mg/kg. We also found that
      the ASR was significantly decreased after 0.03 and 0.1 mg/kg with no change in
      PPI. These results indicate that central plus peripheral cholinesterase
      inhibition (ChEI) decreased ASR, which is contrary to our previous experiments
      with the peripheral ChEI pyridostigmine bromide (PB), suggesting different
      involvement of cholinergic systems in modulating ASR in mice.

PMID- 15582026
TI  - Role of glutamate ionotropic receptors in the dorsomedial hypothalamic nucleus on
      anxiety and locomotor behavior.
AB  - The medial hypothalamus is proposed to play an important role in the modulation
      of defensive responses. Administration of a NMDA receptor antagonist (AP7) into
      the dorsomedial hypothalamic nucleus (DMH) of rats reduced exploratory behavior
      in the open field and elevated plus-maze (EPM), but failed to produce anxiolytic
      effects in the latter test. The objectives of the present work were to test the
      hypotheses that (i) AP7 injections into the DMH would also fail to induce
      anxiolytic effects in another model of anxiety, the Vogel's punished licking
      test; (ii) injection into the DMH of other glutamate ionotropic antagonists would
      also decreased exploratory behavior; and (iii) the decrease in exploratory
      activity found after AP7 administration into the DMH does not involve any gross
      locomotor impairment. Male Wistar rats (n=5-16/group) with cannulas aimed at the
      DMH were submitted to the following behavioral tests: EPM, Vogel, catalepsy and
      rota-rod. Diazepam (3 mg/kg) and haloperidol (2.5 mg/kg) were used as positive
      controls in the Vogel, rota-rod and catalepsy tests. AP7 failed to modify the
      number of punished licks in the Vogel test. It also did not induce any change on
      the rota-rod and catalepsy tests. Diazepam increased the number of punished licks
      and reduced the latency to fall in the rota-rod. Both 7-chlorokynurenic acid (4-8
      nmol), an antagonist of the glycine competitive site in the NMDA receptor and 2,3
      dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]-quinoxaline-7-sulphonamide (NBQX, 1-10
      nmol), a non-NMDA receptor antagonist, decreased the total distance moved in the
      EPM. The former compound also decreased open arm exploration at the dose of 4
      nmol. The results suggest that the antagonism of ionotropic glutamate receptors
      in the DMH does not induce anxiolytic effects in the EPM or Vogel tests, but
      decreases exploratory behavior in a new environment.

PMID- 15582027
TI  - Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model
      of juvenile absence epilepsy.
AB  - The succinic semialdehyde dehydrogenase (SSADH) null mouse represents a viable
      animal model for human SSADH deficiency and is characterized by markedly elevated
      levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA)
      in brain, blood, and urine. GHB is known to induce absence-like seizures and
      absence seizures have been reported to occur in children with SSADH deficiency.
      We tested the hypothesis that the phenotype of the SSADH(-/-) mouse shows absence
      like seizures because of the inordinately high levels of GHB in the brain of this
      mutant animal. Sequential electrocorticographic (ECoG) and prolonged video ECoG
      recordings from chronically implanted electrodes were done on SSADH(-/-),
      SSADH(+/-), and SSADH(+/+) mice from postnatal day (P) 10 to (P) 21. Spontaneous,
      recurrent absence-like seizures appeared in the SSADH(-/-) during the second week
      of life and evolved into generalized convulsive seizures late in the third week
      of life that were associated with an explosive onset of status epilepticus which
      was lethal. The seizures in SSADH null mice were consistent with typical absence
      seizures in rodent with 7 Hz spike-and-wave discharge (SWD) recorded from
      thalamocortical circuitry, the onset/offset of which was time-locked with ictal
      behavior characterized by facial myoclonus, vibrissal twitching and frozen
      immobility. The absence seizures became progressively more severe from P14 to 18
      at which time they evolved into myoclonic and generalized convulsive seizures
      that progressed into a lethal status epilepticus. The absence seizures in SSADH(
      /-) were abolished by ethosuximide (ETX) and the GABA(B)R antagonist CGP 35348.
      The seizure phenotype in the SSADH(-/-) recapitulates that observed in human
      SSADH deficiency. Hence, SSADH(-/-) may be used to investigate the molecular
      mechanisms that underpin the pathogenesis of absence and generalized tonic-clonic
      seizures associated with SSADH deficiency. As well, the SSADH(-/-) may represent
      a unique animal model of the transition from absence to myoclonic and generalized
      convulsive seizures that is observed in up to 80% of patients with juvenile
      absence epilepsy.

PMID- 15582028
TI  - Metoclopramide attenuates iminodipropionitrile-induced oxidative stress and
      neurobehavioral toxicity in rats.
AB  - Metoclopramide (MET) has long been used as a neuroleptic and antiemetic drug in
      clinical practice. Motor impairment and dyskinesia have been reported in some
      patients following chronic treatment with MET. Occasionally, the adverse symptoms
      may appear even after acute exposure to MET in more susceptible population (such
      as elderly individual) or due to concomitant exposure to MET and certain
      neurotoxins. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been
      shown to produce dyskinetic syndrome in rodents. This study reports the effect of
      concomitant exposure of rats to MET and IDPN on behavioral abnormalities in rats
      namely excitation, circling and chorea (ECC) syndrome. Four groups of female
      Wistar rats (aged 3 months) were given MET (0, 10, 40 and 80 mg/kg, i.p., for 11
      days) 30 min before IDPN (100 mg/kg, i.p. for 8 days). Two additional groups of
      rats were treated with either saline (control group) or 80 mg/kg of MET (drug
      alone group). The animals were observed for neurobehavioral abnormalities
      including dyskinetic head movement, circling, tail hanging, air righting reflex
      and contact inhibition of righting reflex. Horizontal and vertical locomotor
      activities and fore limbs grip strength were also measured. On day 12, the
      animals were sacrificed and brains were collected for biochemical analysis. MET
      significantly and dose-dependently protected the animals against IDPN-induced ECC
      syndrome, motor impairment and deficiency in grip strength. MET also protected
      the animals against IDPN-induced oxidative stress.

PMID- 15582029
TI  - Sex differences in mouse behavior following pyrilamine treatment: role of
      histamine 1 receptors in arousal.
AB  - Arousal, the activation of brain and behavior, is a fundamental component of
      behavior. While sex differences in behavior are pervasive, it is unknown whether
      they could be due to an underlying dimorphism in arousal mechanisms. Because
      histamine (HA) acting through histamine 1 (H1) receptors is one essential
      component of arousal neural circuitry, the aim of the current experiment was to
      measure sex differences in behavioral arousal following treatment with the H1
      receptor antagonist, pyrilamine (PYRL). Castrated male and ovariectomized female
      Swiss-Webster mice were treated subcutaneously with either 15 or 35 mg/kg of
      PYRL. The effect of drug treatment was determined in an array of behaviors:
      sensory responsiveness, running wheel activity, and fearfulness. Surprisingly,
      the lower dose of PYRL increased some aspects of arousal, sensory responsiveness,
      and anxiety-like behavior, while the higher dose of PYRL resulted in decreases in
      arousal across tests, indicating that antagonism of histamine receptors does not
      have a linear relationship with arousal. Females were more sensitive to the
      arousal-reducing effects of PYRL than males in sensory and running wheel tasks
      but not in tests of emotion. In conclusion, antagonism of H1 receptors can alter
      arousal in a sex-dependent manner, independent of circulating gonadal steroids,
      in mice.

PMID- 15582030
TI  - Estrogen protects against brain lipid peroxidation in ethanol-withdrawn rats.
AB  - This study examined whether 17beta-estradiol (E2) administration protects against
      ethanol withdrawal (EW)-associated oxidative insults by assessing oxidative
      markers thiobarbituric-acid-reacting-substances (TBARS). Ovariectomized rats
      implanted with E2 (EW/E2) or oil pellets (EW/Oil) received chronic ethanol (7.5%
      wt./vol., 5 weeks) or control dextrin diet (Dextrin/Oil). At 24 or 48 h of EW,
      rats were tested for overt EW signs and the cerebellum, hippocampus, and cortex
      were prepared for TBARS assessment in the presence and absence of FeCl3. For
      control experiments, we assessed E2 effects on blood ethanol concentrations and
      TBARS levels during ethanol exposure prior to EW. The EW/Oil group showed
      enhanced endogenous- and FeCl3-stimulated membrane TBARS levels in the cerebellum
      and hippocampus in a manner inhibited by E2 treatment. There was a relationship
      between the severity of EW and elevation of TBARS levels, particularly in the
      cerebellum. The enhanced TBARS levels at 24 h of EW appeared to diminish at 48 h
      in the hippocampus, but persisted in the cerebellum. E2 treatment did not alter
      blood ethanol concentrations and ethanol exposure alone did not enhance TBARS
      levels. These data suggest that EW rather than ethanol enhances brain lipid
      peroxidation that is transient and brain-region specific. Estrogens protect
      against the brain lipid peroxidation in a manner independent of blood ethanol
      concentrations.

PMID- 15582031
TI  - Effects of intralaminar thalamic stimulation on language functions.
AB  - Fifteen neurosurgical subjects, who were undergoing thalamic chronic electrode
      implants as a treatment for dyskinesia and chronic pain, were evaluated on a
      series of neurolinguistic functions to determine if the stimulation of the
      centromedianum nucleus of the thalamus affected language and cognitive
      processing. Analysis of the data revealed that the stimulation of the left
      centromedianum nucleus had resulted in a notable facilitatory influence on the
      processing of language functions; this facilitatory effect was measured in terms
      of the number of errors produced and the patients' response latency time. The
      facilitatory effect was also noted to have extended to other language functions.
      The nature of the facilitation from the stimulation of the left centromedianum
      nucleus, an extension of the brainstem reticular formation, on language functions
      is discussed.

PMID- 15582032
TI  - Characteristics of auditory agnosia in a child with severe traumatic brain
      injury: a case report.
AB  - We present a case that is unusual in many respects from other documented
      incidences of auditory agnosia, including the mechanism of injury, age of the
      individual, and location of neurological insult. The clinical presentation is one
      of disturbance in the perception of spoken language, music, pitch, emotional
      prosody, and temporal auditory processing in the absence of significant deficits
      in the comprehension of written language, expressive language production, or
      peripheral auditory function. Furthermore, the patient demonstrates relatively
      preserved function in other aspects of audition such as sound localization, voice
      recognition, and perception of animal noises and environmental sounds. This case
      study demonstrates that auditory agnosia is possible following traumatic brain
      injury in a child, and illustrates the necessity of assessment with a wide
      variety of auditory stimuli to fully characterize auditory agnosia in a single
      individual.

PMID- 15582033
TI  - Speech-sound duration processing in a second language is specific to phonetic
      categories.
AB  - The mismatch negativity (MMN) component of the auditory event-related potential
      was used to determine the effect of native language, Russian, on the processing
      of speech-sound duration in a second language, Finnish, that uses duration as a
      cue for phonological distinction. The native-language effect was compared with
      Finnish vowels that either can or cannot be categorized using the Russian
      phonological system. The results showed that the duration-change MMN for the
      Finnish sounds that could be categorized through Russian was reduced in
      comparison with that for the Finnish sounds having no Russian equivalent. In the
      Finnish sounds that can be mapped through the Russian phonological system, the
      facilitation of the duration processing may be inhibited by the native Russian
      language. However, for the sounds that have no Russian equivalent, new vowel
      categories independent of the native Russian language have apparently been
      established, enabling a native-like duration processing of Finnish.

PMID- 15582034
TI  - Finiteness and verb-second in German agrammatism.
AB  - This study presents results from sentence-completion and grammaticality-judgement
      tasks with seven German-speaking agrammatic aphasics and seven age-matched
      control subjects examining verb finiteness marking and verb-second (V2)
      placement. The patients were found to be selectively impaired in tense marking in
      the face of preserved mood and agreement marking. Moreover, our results revealed
      that V2 scores varied across our patients, with some showing impaired and others
      preserved V2 performance. These findings will be discussed in the light of
      different syntactic accounts of agrammatism.

PMID- 15582035
TI  - Rapid serial naming: relations between different stimuli and neuropsychological
      factors.
AB  - We report two studies on rapid serial naming (RSN). Study 1 addressed the
      relations among RSN tasks comprising different stimuli. Separate components for
      RSN of alphanumeric and non-alphanumeric stimuli, as well as for tasks in which
      the stimuli alternated between categories were identified. In Study 2,
      phonological skills, processing speed, motor dexterity, and verbal fluency were
      found to explain RSN performance. The studies indicate: (1) that RSN tasks vary
      in their properties according to the stimuli used and according to the way the
      tasks are arranged, and (2) that RSN tasks are multi-componented.

PMID- 15582036
TI  - Production of graphic symbol sentences by individuals with aphasia: efficacy of a
      computer-based augmentative and alternative communication intervention.
AB  - The study employed a single-subject multiple baseline design to examine the
      ability of 9 individuals with severe Broca's aphasia or global aphasia to produce
      graphic symbol sentences of varying syntactical complexity using a software
      program that turns a computer into a speech output communication device. The
      sentences ranged in complexity from simple two-word phrases to those with
      morphological inflections, transformations, and relative clauses. Overall,
      results indicated that individuals with aphasia are able to access, manipulate,
      and combine graphic symbols to produce phrases and sentences of varying degrees
      of syntactical complexity. The findings are discussed in terms of the clinical
      and public policy implications.

PMID- 15582037
TI  - Reversing spoken items--mind twisting not tongue twisting.
AB  - Using 12 participants we conducted an fMRI study involving two tasks, word
      reversal and rhyme judgment, based on pairs of natural speech stimuli, to study
      the neural correlates of manipulating auditory imagery under taxing conditions.
      Both tasks engaged the left anterior superior temporal gyrus, reflecting
      previously established perceptual mechanisms. Engagement of the left inferior
      frontal gyrus in both tasks relative to baseline could only be revealed by
      applying small volume corrections to the region of interest, suggesting that
      phonological segmentation played only a minor role and providing further support
      for factorial dissociation of rhyming and segmentation in phonological awareness.
      Most importantly, subtraction of rhyme judgment from word reversal revealed
      activation of the parietal lobes bilaterally and the right inferior frontal
      cortex, suggesting that the dynamic manipulation of auditory imagery involved in
      mental reversal of words seems to engage mechanisms similar to those involved in
      visuospatial working memory and mental rotation. This suggests that reversing
      spoken items is a matter of mind twisting rather than tongue twisting and
      provides support for a link between language processing and manipulation of
      mental imagery.

PMID- 15582038
TI  - A mapping theory of agrammatic comprehension deficits.
AB  - This paper offers evidence for the Isomorphic Mapping Hypothesis, which holds
      that individuals with agrammatic aphasia tend to have difficulty comprehending
      sentences in which the order of NPs is not aligned with the structure of the
      corresponding event. We begin by identifying a set of constructions in English
      and Korean for which the IMH makes predictions distinct from those of canonical
      order and trace-based theories of agrammatic comprehension. Then, drawing on data
      involving the interpretation of those patterns by English-speaking and Korean
      speaking agrammatics, we argue for the conceptual and empirical superiority of
      the isomorphic mapping account.

PMID- 15582039
TI  - Thinking beyond deworming.

PMID- 15582040
TI  - Politics, spin, and science.

PMID- 15582041
TI  - Vioxx, the implosion of Merck, and aftershocks at the FDA.

PMID- 15582042
TI  - Buying health in Honduras.

PMID- 15582043
TI  - Rosuvastatin and the statin wars--the way to peace.

PMID- 15582044
TI  - Intramuscular versus oral methylprednisolone in asthma.

PMID- 15582045
TI  - Lighting up cancer cells with "dots".

PMID- 15582046
TI  - Less is more: artificial intelligence and gene-expression arrays.

PMID- 15582048
TI  - Women are catching up, fast--perhaps.

PMID- 15582047
TI  - Climate change, health, and development goals.

PMID- 15582050
TI  - Management of patients with COPD.

PMID- 15582051
TI  - Management of patients with COPD.

PMID- 15582052
TI  - MYSS: should we alter clinical practice?

PMID- 15582053
TI  - Management of patients with COPD.

PMID- 15582055
TI  - Necrotic arachnidism: dispelling fact with fiction.

PMID- 15582056
TI  - Risk factors for and types of oesophageal cancer.

PMID- 15582057
TI  - Restoring high neonatal autopsy rates.

PMID- 15582058
TI  - Why are 4 million newborn babies dying every year?

PMID- 15582059
TI  - Risk of cardiovascular events and rofecoxib: cumulative meta-analysis.
AB  - BACKGROUND: The cyclo-oxygenase 2 inhibitor rofecoxib was recently withdrawn
      because of cardiovascular adverse effects. An increased risk of myocardial
      infarction had been observed in 2000 in the Vioxx Gastrointestinal Outcomes
      Research study (VIGOR), but was attributed to cardioprotection of naproxen rather
      than a cardiotoxic effect of rofecoxib. We used standard and cumulative random
      effects meta-analyses of randomised controlled trials and observational studies
      to establish whether robust evidence on the adverse effects of rofecoxib was
      available before September, 2004. METHODS: We searched bibliographic databases
      and relevant files of the US Food and Drug Administration. We included all
      randomised controlled trials in patients with chronic musculoskeletal disorders
      that compared rofecoxib with other non-steroidal anti-inflammatory drugs (NSAIDs)
      or placebo, and cohort and case-control studies of cardiovascular risk and
      naproxen. Myocardial infarction was the primary endpoint. FINDINGS: We identified
      18 randomised controlled trials and 11 observational studies. By the end of 2000
      (52 myocardial infarctions, 20742 patients) the relative risk from randomised
      controlled trials was 2.30 (95% CI 1.22-4.33, p=0.010), and 1 year later (64
      events, 21432 patients) it was 2.24 (1.24-4.02, p=0.007). There was little
      evidence that the relative risk differed depending on the control group (placebo,
      non-naproxen NSAID, or naproxen; p=0.41) or trial duration (p=0.82). In
      observational studies, the cardioprotective effect of naproxen was small
      (combined estimate 0.86 [95% CI 0.75-0.99]) and could not have explained the
      findings of the VIGOR trial. INTERPRETATION: Our findings indicate that rofecoxib
      should have been withdrawn several years earlier. The reasons why manufacturer
      and drug licensing authorities did not continuously monitor and summarise the
      accumulating evidence need to be clarified.

PMID- 15582060
TI  - Monetary incentives in primary health care and effects on use and coverage of
      preventive health care interventions in rural Honduras: cluster randomised trial.
AB  - BACKGROUND: Scaling-up of effective preventive interventions in child and
      maternal health is constrained in many developing countries by lack of demand. In
      Latin America, some governments have been trying to increase demand for health
      interventions by making direct payments to poor households contingent on them
      keeping up-to-date with preventive health services. We undertook a public health
      programme effectiveness trial in Honduras to assess this approach, contrasting it
      with a direct transfer of resources to local health teams. METHODS: 70
      municipalities were selected because they had the country's highest prevalence of
      malnutrition. They were allocated at random to four groups: money to households;
      resources to local health teams combined with a community-based nutrition
      intervention; both packages; and neither. Evaluation surveys of about 5600
      households were undertaken at baseline and roughly 2 years later. Pregnant women
      and mothers of children younger than 3 years old were asked about use of health
      services (primary outcome) and coverage of interventions such as immunisation and
      growth monitoring (secondary outcome). Reports were supplemented with data from
      children's health cards and government service utilisation data. Analysis was by
      mixed effects regression, accounting for the municipality-level randomisation.
      FINDINGS: The household-level intervention had a large impact (15-20 percentage
      points; p<0.01) on the reported coverage of antenatal care and well-child check
      ups. Childhood immunisation series could thus be started more opportunely, and
      the coverage of growth monitoring was markedly increased (15-21 percentage
      points; p<0.01. Measles and tetanus toxoid immunisation were not affected. The
      transfer of resources to local health teams could not be implemented properly
      because of legal complications. INTERPRETATION: Conditional payments to
      households increase the use and coverage of preventive health care interventions.

PMID- 15582061
TI  - Effects of repeated prenatal ultrasound examinations on childhood outcome up to 8
      years of age: follow-up of a randomised controlled trial.
AB  - BACKGROUND: Despite the widespread use of prenatal ultrasound studies, there are
      no published data from randomised controlled trials describing childhood outcomes
      that might be influenced by repeated ultrasound exposures. We previously
      undertook a randomised controlled trial to assess the effects of multiple studies
      on pregnancy and childhood outcomes and reported that those pregnancies allocated
      to receive multiple examinations had an unexplained and significant increase in
      the proportion of growth restricted newborns. Our aim was to investigate the
      possible effects of multiple prenatal ultrasound scans on growth and development
      in childhood. Here, we provide follow-up data of the childrens' development.
      METHODS: Physical and developmental assessments were done on children whose
      pregnant mothers had been allocated at random to a protocol of five studies of
      ultrasound imaging and umbilical artery Doppler flow velocity waveform between 18
      and 38 weeks' gestation (intensive group n=1490) or a single imaging study at 18
      weeks' gestation (regular group n=1477). We used generalised logistic and linear
      regression models to assess the group differences in developmental and growth
      outcomes over time. Primary data analysis was done by intention-to-treat.
      FINDINGS: Examinations were done at 1, 2, 3, 5, and 8 years of age on children
      born without congenital abnormalities and from singleton pregnancies (intensive
      group n=1362, regular group n=1352). The follow-up rate at 1 year was 85%
      (2310/2714) and at 8 years was 75% (2042/2714). By 1 year of age and thereafter,
      physical sizes were similar in the two groups. There were no significant
      differences indicating deleterious effects of multiple ultrasound studies at any
      age as measured by standard tests of childhood speech, language, behaviour, and
      neurological development. INTERPRETATION: Exposure to multiple prenatal
      ultrasound examinations from 18 weeks' gestation onwards might be associated with
      a small effect on fetal growth but is followed in childhood by growth and
      measures of developmental outcome similar to those in children who had received a
      single prenatal scan.

PMID- 15582062
TI  - The eye in neurological disease.
AB  - Neurological disease can involve the eye in many ways. Every structure--the
      conjunctiva, cornea, anterior chamber, iris, lens, vitreous humour, retina,
      choroid, and optic nerve--can be affected. In many cases, ocular involvement is
      the first manifestation of the underlying disease. In such cases, the ability of
      the physician to recognise the nature and significance of the ocular abnormality
      can lead to early diagnosis and successful treatment of the underlying condition.
      In other cases, recognition of the ocular abnormality can prevent permanent
      visual dysfunction.

PMID- 15582063
TI  - Microscopic colitis: a missed diagnosis?
AB  - CONTEXT: Collagenous colitis and lymphocytic colitis, collectively designated
      microscopic colitis, have until recently been considered as rare gastrointestinal
      disorders. New data suggest, however, that these disorders are relatively common,
      and to reach the correct diagnosis both the gastroenterologist and the
      pathologist must be aware of these diagnoses when evaluating patients with
      persistent watery non-bloody diarrhoea. STARTING POINT: In an epidemiological
      study of a well-defined Swedish population, Martin Olesen and colleagues show
      that microscopic colitis needs to be considered as a common gastrointestinal
      disorder (Gut 2004; 53: 346-50). In colonic biopsy specimens from 1018 patients
      who had a colonoscopy because of non-bloody diarrhoea in 1993-98, 97 patients
      (9.5%) were found to have microscopic colitis. In about a third of these cases,
      the diagnosis was missed in the primary histological evaluation. Median age at
      diagnosis was 64 years for collagenous colitis and 59 years for lymphocytic
      colitis. The annual incidence of the diseases was higher than previously
      considered and matched the incidence of Crohn's disease, and in combination they
      approached the incidence of ulcerative colitis. WHERE NEXT: The high regional
      incidence of microscopic colitis means that both clinicians and pathologists need
      to be more aware of the diagnosis, especially in the elderly female population
      with a clinical picture of watery non-bloody diarrhoea. Because of the
      potentially disabling symptoms, clinicians need to develop and evaluate new
      therapies.

PMID- 15582064
TI  - Mental health in complex emergencies.
AB  - Mental health is becoming a central issue for public health complex emergencies.
      In this review we present a culturally valid mental health action plan based on
      scientific evidence that is capable of addressing the mental health effects of
      complex emergencies. A mental health system of primary care providers,
      traditional healers, and relief workers, if properly trained and supported, can
      provide cost-effective, good mental health care. This plan emphasises the need
      for standardised approaches to the assessment, monitoring, and outcome of all
      related activities. Crucial to the improvement of outcomes during crises and the
      availability to future emergencies of lessons learned from earlier crises is the
      regular dissemination of the results achieved with the action plan. A research
      agenda is included that should, in time, fill knowledge gaps and reduce the
      negative mental health effects of complex emergencies.

PMID- 15582065
TI  - CJD--a case of mistaken identity.

PMID- 15582066
TI  - Sebaceous carcinoma of the eyelids.

PMID- 15582067
TI  - Sebaceous carcinoma of the eyelids: personal experience with 60 cases.
AB  - OBJECTIVE: To describe clinical features, management, and prognosis of sebaceous
      carcinoma of the eyelid and adjacent structures. DESIGN: Single-center
      retrospective interventional case series. PARTICIPANTS: Sixty consecutive
      patients with sebaceous carcinoma of the eyelid and adjacent structures. METHODS:
      Retrospective chart review and literature review. MAIN OUTCOME MEASURES:
      Presenting features, sites of origin, location, growth patterns, management,
      histopathologic findings, incidence of recurrence, metastasis, and mortality.
      RESULTS: The median age at referral was 72 years, with 73% female. Four patients
      had prior irradiation to the area where the sebaceous carcinoma developed.
      Initial clinical diagnoses elsewhere were sebaceous carcinoma (32%),
      blepharoconjunctivitis (25%), chalazion (20%), basal cell carcinoma (13%), and
      squamous cell carcinoma (10%). Initial histopathologic diagnoses elsewhere were
      sebaceous carcinoma (50%), squamous cell carcinoma (18%), basal cell carcinoma
      (8%), and others or not available (24%). Initial anatomic sites were upper eyelid
      (75%), lower eyelid (22%), caruncle (2%), and bulbar conjunctiva (2% [1 case]).
      Orbital exenteration was necessary in 13%. Recently introduced techniques of
      posterior lamellar resection of the eyelids with reconstruction (7%) hopefully
      will decrease this incidence in the future. Pathologically, 47% showed
      intraepithelial (pagetoid) involvement, 27% of sebaceous carcinomas arose from
      the meibomian glands, and 18% arose from both meibomian and Zeis glands. Local
      recurrence developed in 18%, metastasis in 8%, and death from metastasis in 6%.
      CONCLUSIONS: Despite the fact that the clinical features of sebaceous carcinoma
      have been widely reported, the diagnosis was suspected initially in only 32% of
      patients at first examination elsewhere and in only 50% at histopathologic
      examination elsewhere. Orbital exenteration was necessary in 13%, mostly patients
      seen in the earlier years of the study. With more recently employed treatment
      methods, there is a tendency to avoid exenteration and to use more conservative
      methods of treatment. It is hoped that these modern therapeutic approaches will
      result in fewer cases of recurrence and metastasis.

PMID- 15582068
TI  - Efficacy and efficiency of a small-incision, minimal dissection procedure versus
      a traditional approach for correcting aponeurotic ptosis.
AB  - OBJECTIVE: To compare the efficacy and efficiency of a new small anterior
      incision, minimal dissection ptosis procedure with that of a traditional anterior
      aponeurotic approach for the correction of aponeurotic ptosis. DESIGN:
      Retrospective, comparative, interventional case series. PARTICIPANTS: Seventy-two
      patients with aponeurotic ptosis who had undergone ptosis correction surgery by 1
      surgeon: 36 patients (49 ptotic eyelids) who had ptosis correction by a small
      incision, minimal dissection procedure and 36 patients (49 ptotic eyelids) who
      had ptosis correction by a traditional aponeurotic approach. METHODS: Charts and
      available photographs were reviewed for each patient. MAIN OUTCOME MEASURES:
      Postoperative upper eyelid height relative to the center of the pupil and
      relative to the opposite upper eyelid and the postoperative eyelid contour.
      RESULTS: Successful correction of the eyelid height and the rate of recommended
      reoperation were not significantly different for the 49 lids corrected in each
      arm of the study. The incidence of attaining good eyelid contour was
      significantly better in the small incision group, in which 41 of 42 lids (97.6%)
      evaluated by photographs had good contour compared with 29 of 37 lids (78.4%) in
      the traditional group. Operating time per lid was significantly less for the
      small-incision, minimal dissection group, 25.3+/-13.0 minutes (range, 13-68
      minutes) compared with 55.4+/-16.6 minutes (range, 35-119) for the traditional
      group. CONCLUSIONS: The small-incision, minimal dissection technique for ptosis
      correction is equally effective in correcting eyelid height, superior in
      producing desirable eyelid contour, and much quicker to perform than the
      traditional aponeurotic approach.

PMID- 15582069
TI  - Modified Hughes flap: division at 7 days.
AB  - PURPOSE: To report the outcome of early division of the tarsoconjunctival pedicle
      of a modified Hughes flap at 1 week after the primary operation. DESIGN:
      Noncomparative, interventional, prospective case series. PARTICIPANTS: Twenty
      nine eyelids of 29 consecutive patients operated using the modified Hughes flap
      and full-thickness skin graft for lower eyelid reconstruction after Mohs
      micrographic surgery, over a 4-year period. INTERVENTION: In all patients, the
      pedicle of the Hughes flap was divided 1 week after the primary operation. MAIN
      OUTCOME MEASURES: Postoperative lower eyelid flap viability and lower eyelid
      contour complications. RESULTS: Twenty-nine eyelids of 29 patients (mean age:
      69+/-11 years) were operated using the modified Hughes flap. The mean follow-up
      period was 14+/-6 months (range: 6-23). There were no cases of lower eyelid
      retraction, flap ischemia, or necrosis after division. Postoperative
      complications included lower eyelid margin erythema in 2 patients (6.9%), upper
      eyelid lash ptosis in 3 patients (10.3%), and upper eyelid lateral retraction in
      1 patient (3.4%). CONCLUSION: Early division of the tarsoconjunctival pedicle of
      a modified Hughes flap at 1 week does not compromise the viability of the
      reconstructed lower eyelid and results in a good functional and cosmetic outcome.

PMID- 15582070
TI  - Undercorrected refractive error in Singaporean Chinese adults: the Tanjong Pagar
      survey.
AB  - OBJECTIVE: To study the prevalence of undercorrected refractive error and
      associated sociodemographic factors among Singaporean Chinese adults. DESIGN:
      Cross-sectional, population-based survey. PARTICIPANTS: Singaporean Chinese
      adults aged 40 to 79 years (n = 1152). METHODS: The Singapore electoral register
      of Tanjong Pagar was used as a sampling frame, and disproportionate, stratified,
      clustered, random sampling was performed. There were 1717 eligible adults and
      1232 (71.8%) participated. Analysis was performed among 1152 adults with complete
      habitual and best-corrected visual acuity data. MAIN OUTCOME MEASURE:
      Undercorrected refractive error was defined as improvement of better eye visual
      acuity of at least 2 lines or more with best possible refractive correction.
      RESULTS: The age- and gender-adjusted rate of undercorrected refractive error
      standardized directly by age and gender was 17.3% (95% confidence interval, 15.0,
      19.5). Undercorrected refractive error rates were more common in older adults who
      had completed fewer years of education and in those who had cataract. People who
      did not wear spectacles tended to have poorer vision. CONCLUSIONS: The
      undercorrected refractive error rate among Singaporean Chinese is relatively
      common compared with data from other populations.

PMID- 15582071
TI  - Wavefront-guided LASIK with the Zyoptix 3.1 system for the correction of myopia
      and compound myopic astigmatism with 1-year follow-up: clinical outcome and
      change in higher order aberrations.
AB  - OBJECTIVE: To assess safety, efficacy, predictability, stability, and change in
      aberrations after wavefront-guided LASIK for myopia and myopic astigmatism.
      DESIGN: Prospective, nonrandomized, self-controlled trial. PARTICIPANTS:
      Wavefront-guided LASIK was performed in 97 eyes in a 1-year trial. Treated eyes
      had a mean subjective manifest spherical equivalent (SE) of -5.22+/-2.07 diopters
      (D), with a range of -0.25 to -9.00 D of myopia and 0 to -3.25 D of astigmatism.
      INTERVENTION: After a microkeratome cut, a wavefront-based excimer ablation
      (Zyoptix 3.1) was performed. The full treatment to achieve emmetropia of an early
      nomogram provided by the system manufacturer was used in all procedures. MAIN
      OUTCOME MEASURES: Safety, efficacy, predictability, and stability were evaluated
      at 1, 3, and 12 months postoperatively. Wavefront changes of higher order
      aberrations (HOAs) at 1 year were determined for pupil sizes of 3.5 and 6 mm.
      RESULTS: At 1 year postoperatively, uncorrected visual acuity (VA) was 20/20 or
      better in 83% of the eyes, and 20/40 or better in 98%. The mean subjective
      manifest SE at 1 year was -0.25+/-0.43 D; it was within 0.50 D in 77% and within
      1.0 D in 95%. No eye lost > or =2 lines of best spectacle-corrected VA (BSCVA) at
      1 year postoperatively; 40 eyes gained 1 line of BSCVA, and 5 eyes gained 2
      lines. The total HOA root mean square (RMS) increased on average by a factor of
      1.23+/-0.57 with a 3.5-mm pupil; for the 6 mm pupil, the increase factor was
      1.52+/-0.36. No change or reduction in the total HOA RMS was observed in 45.5% of
      the eyes for a 3.5-mm pupil and in 20.6% for a 6-mm pupil. There was a
      significant increase of primary spherical aberration (Z 4,0) by a factor of
      4.11+/-10.17 for 3.5-mm pupils and 4.31+/-6.76 for 6-mm pupils. CONCLUSIONS:
      Wavefront-guided LASIK using Zyoptix 3.1 is an effective and safe procedure for
      the treatment of myopia and myopic astigmatism. Although in close to half of the
      eyes HOAs could be reduced, there was still undercorrection and induction of HOAs
      with the algorithm employed.

PMID- 15582072
TI  - Conjunctival epithelial cell expression of interleukins and inflammatory markers
      in glaucoma patients treated over the long term.
AB  - PURPOSE: To compare the conjunctival epithelial cell expressions of inflammatory
      cytokines in normal subjects and in glaucoma patients treated over the long term.
      DESIGN: Case-control study. PARTICIPANTS: A total of 69 glaucoma patients treated
      over the long term and 15 normal subjects with no ocular abnormality or topical
      treatment. METHODS: Amongst the 69 glaucoma patients, 27 were treated with
      preserved beta-blockers, 24 with unpreserved 0.5% timolol, and the other 18
      patients with an association of > or =2 preserved drugs. All patients were
      treated for more than 1 year with the same treatment, with no significant
      differences between groups for mean ages and durations of treatment at the time
      of the study. Impression cytology specimens were taken and processed for
      immunofluorescence techniques. Conjunctival cell expressions of HLA DR, as a
      standard for inflammatory level, and the interleukins IL-6, IL-8, and IL-10 were
      obtained and quantified using flow cytometry. MAIN OUTCOME MEASURES: Immune
      markers and proinflammatory cytokines in impression cytology specimens. RESULTS:
      We found a significantly increased expression of all immunoinflammatory markers
      and mediators in the conjunctival epithelium of glaucoma patients compared with
      normal eyes. Human leukocyte antigen DR was significantly higher in the 2 groups
      receiving preserved drugs than in the unpreserved timolol group. The 3
      interleukins were similarly overexpressed in all glaucoma groups, with no
      significant between-groups differences except for the expression level of IL-8,
      which was significantly higher in the multitreatment group than in the
      preservative-free one. CONCLUSIONS: The present study confirms the increased
      expression of immunoinflammatory markers by the conjunctival epithelium of
      glaucoma patients treated over the long term. The development of nontoxic
      preservatives or preservative-free solutions is therefore of great interest.

PMID- 15582073
TI  - Detection of the free acid of bimatoprost in aqueous humor samples from human
      eyes treated with bimatoprost before cataract surgery.
AB  - PURPOSE: To determine whether bimatoprost is hydrolyzed to its free acid after
      topical application in humans in vivo. DESIGN: Prospective, masked, and vehicle
      controlled. PARTICIPANTS: Thirty-one eyes of 31 patients with cataracts. METHODS:
      Beginning 7 days before scheduled cataract surgery, one eye of each patient was
      treated with bimatoprost 0.03% or vehicle once daily, with the last drop
      administered 2 to 12 hours before anterior chamber paracentesis before cataract
      surgery. In a masked fashion, aqueous humor specimens were assayed for
      bimatoprost and its free acid by high-pressure liquid chromatography and mass
      spectrometry. MAIN OUTCOME MEASURE: Detection of the free acid of bimatoprost in
      aqueous humor. RESULTS: Aqueous humor concentrations of the free acid of
      bimatoprost were 22.0+/-7.0 nmol/l (mean +/- standard error of the mean, n = 12)
      and 7.0+/-4.6 nmol/l (n = 8) at 2 and 12 hours, respectively, and below the limit
      of detection after vehicle (n = 10). Concentrations of bimatoprost (amide) were
      5.7+/-1.4 and 1.1+/-0.4 nmol/l at 2 and 12 hours, respectively, and undetectable
      after vehicle. CONCLUSION: After topical application of bimatoprost in humans, a
      sufficient concentration of its free acid, a potent FPprostanoid receptor
      agonist, is found in the aqueous humor to account for its ability to reduce
      intraocular pressure.

PMID- 15582074
TI  - Scanning laser polarimetry of the retinal nerve fiber layer in perimetrically
      unaffected eyes of glaucoma patients.
AB  - PURPOSE: To compare scanning laser polarimetry (SLP) measurements of retinal
      nerve fiber layer (RNFL) thickness in perimetrically unaffected eyes of glaucoma
      patients with those in their fellow eyes with field loss and eyes of healthy
      subjects. DESIGN: Observational case-control study. PARTICIPANTS AND CONTROLS:
      Twenty-three glaucoma patients with a reproducible visual field (VF) defect in
      one eye (mean mean deviation [MD], -5.71 decibels [dB]) and a normal VF in the
      other one (i.e., < or =1 VF test point below the 5% probability level [mean MD, 
      0.01 dB]) and 73 control eyes of as many age-matched healthy subjects (mean MD,
      0.39 dB). The MDs and pattern standard deviations of the glaucoma patients' eyes
      with normal VFs and the control eyes did not statistically significantly differ
      (independent samples t test, P = 0.15 and P = 0.61, respectively). METHODS: All
      subjects were measured in both eyes with the GDxVCC, a commercially available
      instrument featuring SLP with automated variable corneal compensation. Standard
      automated perimetry was assessed by means of the Humphrey Field Analyzer (24-2
      Full Threshold or Swedish interactive threshold algorithm Standard achromatic
      test program). MAIN OUTCOME MEASURES: The standard GDxVCC parameters TSNIT
      (temporal, superior, nasal, inferior, temporal) Average, Superior Average,
      Inferior Average, TSNIT Std. Dev., and Nerve Fiber Indicator (NFI) were
      determined. We also assessed the thickness values in 6 parapapillary sectors. In
      addition, we calculated the proportion of eyes per group with an NFI of > or =40.
      RESULTS: GDxVCC measurements showed more RNFL thinning in the perimetrically
      unaffected eyes of glaucoma patients than in the healthy control eyes. The RNFL
      in the perimetrically unaffected eyes of glaucoma patients was thicker than that
      in their fellow eyes with field loss. The NFI had a value of > or =40 in 11 of 23
      (47.8%) perimetrically unaffected eyes of glaucoma patients, 19 of 23 (82.6%)
      eyes with VF loss of glaucoma patients, and 3 of 73 (4.1%) healthy control eyes.
      CONCLUSION: With the GDxVCC, thinning of the RNFL may be detected in
      perimetrically unaffected eyes of glaucoma patients with field loss in their
      fellow eyes.

PMID- 15582075
TI  - Baerveldt glaucoma implant in the management of refractory childhood glaucomas.
AB  - PURPOSE: To evaluate the effectiveness and safety of the Baerveldt glaucoma
      drainage implant (GDI) in the management of pediatric glaucomas. DESIGN:
      Retrospective noncomparative case series. PARTICIPANTS: Sixty-two children
      younger than 18 years who underwent Baerveldt GDI surgery. MAIN OUTCOME MEASURES:
      Intraocular pressure (IOP), intraoperative and postoperative complications,
      number of glaucoma medications, and VA. Success was defined as IOP of <22 mmHg
      and > or =5 mmHg with or without medications, no loss of light perception, and no
      further surgical intervention for glaucoma. Outcomes were compared for patients
      with primary and secondary glaucomas. RESULTS: Sixty-two eyes of 62 patients were
      identified. The mean patient age (+/- standard deviation) at time of Baerveldt
      glaucoma implant surgery was 6.5+/-5.6 years (range, 6 weeks-17 years). With an
      average follow-up of 23.4+/-21.7 months (range, 1-106), IOP was reduced from a
      mean of 35.0+/-8.7 mmHg (range, 17-54) preoperatively to 17.6+/-8.4 mmHg (range,
      5-45) at last follow-up visit (P<0.001). Kaplan-Meier survival analysis showed a
      cumulative success of 85% at 6 months, 80% at 12 months, 67% at 24 months, and
      60% in months 28 through 106. There was no difference between primary (N = 23)
      and secondary glaucoma (N = 39) patients in terms of length of follow-up, final
      IOP, number of medications, or cumulative success (P = 0.21). CONCLUSION:
      Baerveldt glaucoma implant surgery seems to be an effective treatment for primary
      and secondary refractory glaucomas in children. There is a risk of retinal
      detachment that may be related to the implant or other ocular conditions.

PMID- 15582076
TI  - Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African
      Americans, and Japanese in a glaucoma clinic.
AB  - OBJECTIVE: To characterize the central corneal thickness (CCT) of Asian (Chinese,
      Japanese, and Filipino), Caucasian, Hispanic, and African American patients in a
      multiethnic glaucoma practice. DESIGN: Retrospective study (chart review).
      PARTICIPANTS: Glaucomatous (n = 600) and nonglaucomatous (n = 201) eyes of 801
      patients examined in a San Francisco glaucoma clinic from June 2002 to April 2004
      who met inclusion criteria were included in the study. The 6 racial (ethnic)
      groups represented in the study were Caucasian (n = 186, 23.2%), Chinese (n =
      157, 19.6%), Japanese (n = 121, 15.1%), Hispanic (n = 116, 14.5%), Filipino (n =
      114, 14.2%), and African American (n = 107, 13.4%). METHODS: Central corneal
      thickness was measured by means of ultrasound pachymetry in Asian (Chinese,
      Japanese, and Filipino), Caucasian, Hispanic, and African American participants
      with glaucomatous and normal eyes. The relationship between CCT and race was
      investigated using multivariate regression analyses, controlling for confounders.
      One eye of each of 801 participants was included for analysis. MAIN OUTCOME
      MEASURES: Correlation of mean CCT with race, glaucoma diagnosis, age, spherical
      equivalent, gender, and history of ocular surgery. RESULTS: The mean CCT of all
      participants was 542.9 mum. Central corneal thicknesses of Chinese (555.6
      microm), Caucasian (550.4 microm), Filipino (550.6 microm), and Hispanic (548.1
      microm) participants did not significantly differ. The CCT of Japanese
      participants (531.7 microm) was significantly less than that of Caucasians,
      Chinese, Filipinos, and Hispanics (all, P< or =0.001) and greater than that of
      African Americans (P = 0.03). African Americans had a CCT (521.0.0 microm) less
      than that of all races (P< or =0.05). Glaucoma suspects and patients with normal
      tension glaucoma (NTG), primary open-angle glaucoma (POAG), pseudoexfoliation
      glaucoma (PEX), and chronic angle-closure glaucoma (CACG) had corneas
      significantly thinner than those of normal participants (P< or =0.004), whereas
      ocular hypertensives had significantly thicker corneas (P<0.0001). Among all
      participants, decreasing values of CCT were significantly related to older age
      (P<0.01). Less negative or more positive refractive errors, gender, and history
      of ocular surgery were not associated with changes in CCT (P = 0.38, P = 0.50,
      and P = 0.97, respectively). CONCLUSIONS: Studies examining individual Asian
      subpopulations in isolation suggest that differences in CCT may exist among
      different Asian groups. The results of this study indicate that CCT does, in
      fact, vary among Asian subpopulations; Japanese have thinner corneas than Chinese
      and Filipinos. Caucasians, Chinese, Hispanics, and Filipinos have comparable CCT
      measurements, whereas the corneas of African Americans are significantly thinner.
      Additionally, older individuals; glaucoma suspects; and participants with NTG,
      POAG, PEX, and CACG have thinner corneas. Ocular hypertensives, however, have
      thicker corneas.

PMID- 15582077
TI  - Central corneal thickness and its relationship to intraocular pressure in
      children.
AB  - OBJECTIVE: Central corneal thickness (CCT) has emerged as an important predictive
      factor for the development of glaucomatous damage. Although a child's cornea
      reaches adult thickness by the age of 3, little has been reported about normal
      CCT measurements in eyes of children. We wished to test the hypotheses that (1)
      there is a correlation between increasing CCT and increasing intraocular pressure
      (IOP) in the eyes of children, (2) the CCT in the eyes of children with ocular
      hypertension is greater than that in eyes of normal pediatric subjects, and (3)
      the average CCT of black children is less than that of white children. METHODS:
      We performed a retrospective chart review of 69 pediatric patients seen in the
      office of one ophthalmologist between January 1997 and December 2001 in whom CCT
      was measured by ultrasound pachymetry. We categorized the subjects into
      diagnostic groups of controls, glaucoma, glaucoma suspects, and ocular
      hypertension based on IOP, cup-to-disc ratio, and visual field parameters.
      RESULTS: The average CCT for the control patients was 555+/-37 microm; for
      patients with glaucoma, it was 563+/-33 microm; for glaucoma suspects, 559+/-39
      microm; and for those with ocular hypertension, 595+/-39 microm. The difference
      between the control and ocular hypertensive groups was significant (P<0.02). The
      difference in CCT between the black control subjects and the white ones (537+/-36
      microm vs. 564+/-28 microm) was not statistically significant (P = 0.125).
      CONCLUSIONS: Central corneal thickness is greater in children with ocular
      hypertension than in control subjects or those with glaucoma, and the values for
      CCT in these children correlate closely with values reported for adults. Corneas
      of black children may be thinner than the corneas of white children.

PMID- 15582078
TI  - Course of cytomegalovirus retinitis in the era of highly active antiretroviral
      therapy: 1. Retinitis progression.
AB  - PURPOSE: To describe the course of cytomegalovirus (CMV) retinitis in patients
      with AIDS in the era of highly active antiretroviral therapy (HAART). DESIGN:
      Multicenter, prospective, observational study. PARTICIPANTS: Two hundred seventy
      one patients with AIDS and CMV retinitis. METHODS: Follow-up every 3 months with
      medical history, ophthalmologic examination, laboratory testing, and fundus
      photographs. Photographs were evaluated for relapse of the retinitis
      (progression) by graders at a centralized reading center. MAIN OUTCOME MEASURE:
      Retinitis progression (movement of the border of a CMV lesion > or =750 microm
      over a > or =750-microm front or occurrence of a new lesion one-quarter disc area
      or more in size). RESULTS: The overall rate of retinitis progression was
      0.10/person-year (PY); among those with CD4+ T-cell counts of <50/microl, it was
      0.58/PY, compared to 0.02/PY among those with CD4+ T-cell counts of > or
      =200/microl (P<0.0001). In the multivariate analysis, significant risk factors
      for retinitis progression included a low CD4+ T-cell count, positive CMV load,
      longer time from AIDS diagnosis, and low Karnofsky score. CONCLUSIONS: Compared
      with the rate of retinitis progression (approximately 3.0/PY) reported in the pre
      HAART era, the rate of retinitis progression was reduced among patients in the
      HAART era, even among those with low CD4+ T-cell counts, who might be expected to
      behave most like patients from the pre-HAART era. However, these events also
      occurred among patients with high CD4+ T-cell counts and presumed immune
      recovery. Continued ophthalmologic follow-up of patients with immune recovery is
      recommended to detect early retinitis progression.

PMID- 15582079
TI  - Course of cytomegalovirus retinitis in the era of highly active antiretroviral
      therapy: 2. Second eye involvement and retinal detachment.
AB  - PURPOSE: To describe the course of cytomegalovirus (CMV) retinitis in patients
      with AIDS in the era of highly active antiretroviral therapy (HAART). DESIGN:
      Multicenter, prospective, observational study. PARTICIPANTS: Two hundred seventy
      one patients with AIDS and CMV retinitis. METHODS: Follow-up every 3 months with
      medical history, ophthalmologic examination, laboratory testing, and fundus
      photographs. MAIN OUTCOME MEASURE: Second (contralateral) eye involvement among
      patients with unilateral disease and retinal detachment (RD). RESULTS: The
      overall rate of second eye involvement among patients with unilateral CMV
      retinitis was 0.07 per person-year (PY); among those with CD4+ T-cell counts of
      <50/microl it was 0.34/PY, compared with 0.02/PY among those with CD4+ T-cell
      counts of > or =200/microl (P<0.0001). Risk factors for contralateral eye
      involvement included low CD4+ T-cell count and detectable CMV load. The overall
      rate of RD was 0.06/PY; among those with CD4+ T-cell counts of <50/microl it was
      0.30/PY, compared with 0.02/PY among those with CD4+ T-cell counts of > or
      =200/microl (P<0.0001). Risk factors for RD included a low CD4+ T-cell count and
      larger area of CMV retinitis. CONCLUSIONS: Compared with the rates reported in
      the pre-HAART era of second eye involvement (approximately 0.40/PY) and RD
      (approximately 0.50/PY), the rates of these events were reduced among patients in
      the HAART era. However, among patients with CD4+ T-cell counts of <50/microl, the
      rates were more similar to those from the pre-HAART era.

PMID- 15582080
TI  - A randomized controlled trial of combined 5-fluorouracil and low-molecular-weight
      heparin in management of established proliferative vitreoretinopathy.
AB  - OBJECTIVE: To determine the efficacy of a combination of 5-fluorouracil and low
      molecular-weight heparin (LMWH) to improve the outcome of surgery for established
      proliferative vitreoretinopathy (PVR). DESIGN: Double-masked, prospective,
      randomized, placebo-controlled clinical trial. SETTING: Three tertiary-referral
      teaching hospital vitreoretinal surgical units. PATIENTS: One hundred fifty-seven
      patients with established PVR (grade C, anterior or posterior) undergoing
      vitrectomy surgery. INTERVENTION: All patients underwent vitreoretinal surgery
      and silicone oil exchange with or without membrane peeling and/or retinectomy.
      Patients were randomly allocated to perioperative infusion with or without 5
      fluorouracil (200 microg/ml) and LMWH (5 IU/ml) in Hartmann's solution for 1
      hour. OUTCOME MEASURES: The primary outcome measure was defined as posterior
      retinal reattachment after removal of silicone oil without any reoperations at 6
      months. Secondary outcome measures recorded were posterior retinal reattachment,
      localized/tractional retinal detachment, visual acuity, macular pucker, hypotony,
      glaucoma, keratopathy, and cataract. Removal of silicone oil and reoperations
      were also recorded. RESULTS: Overall, at 6 months 84% of patients had full
      retinal reattachment and 94% had stable posterior retinal reattachment. There was
      no significant difference in success in the primary outcome measure (56%,
      treatment group; 51%, placebo group; P = 0.59) or in secondary outcome measures
      or rates of complications. Secondary macular pucker occurred less often in the
      treatment group (6% vs. 17% at 6 months, P = 0.068). CONCLUSIONS: A perioperative
      infusion of combined 5-fluorouracil and LMWH does not significantly increase the
      success rate of vitreoretinal surgery for established PVR.

PMID- 15582081
TI  - Long-term follow-up of indocyanine green-assisted peeling of the retinal internal
      limiting membrane during vitrectomy surgery for idiopathic macular hole repair.
AB  - OBJECTIVE: To determine the long-term efficacy of indocyanine green (ICG)
      assisted retinal internal limiting membrane (ILM) peeling during macular hole
      repair. DESIGN: Retrospective, interventional, noncomparative case series.
      PARTICIPANTS: One hundred twenty-one eyes of 114 patients with stage 2, 3, or 4
      idiopathic macular holes that underwent ICG-assisted macular hole repair during
      the period of August 1999 to January 2003. INTERVENTION: All eyes underwent a
      pars plana vitrectomy, including peeling of the posterior cortical hyaloid when
      necessary. Indocyanine green dye (0.5%) was instilled over the macula, and after
      removal of the ICG, the retinal ILM was peeled. Medium- to long-acting gas
      tamponade was used in all cases, and all patients were asked to position
      themselves facedown for 1 to 2 weeks. MAIN OUTCOME MEASURES: Long-term
      postoperative anatomic results, visual acuity (VA), and complications. RESULTS:
      Patients were observed postoperatively for an average of 26 months (range, 12
      53). Anatomic closure of the macular hole was achieved in 118 eyes (98%) with a
      single surgery. Reoperation was successful at closing 2 of the 3 macular holes
      that did not close initially. One macular hole reopened 16 months after the
      original surgery, and the patient has not yet undergone further surgery. Visual
      acuity improved by > or =2 lines in 116 eyes (96%). Mean visual improvement after
      surgery was 6 lines (range, 0-14), and 96 eyes (79%) achieved a final VA of 20/50
      or better. There were no intraoperative or postoperative complications attributed
      to the use of ICG. CONCLUSIONS: Long-term follow-up of patients who underwent ICG
      assisted ILM peeling for idiopathic macular hole repair demonstrates excellent
      anatomic and visual results.

PMID- 15582082
TI  - Geographic disparities in diagnostic screening for metastatic uveal melanoma.
AB  - PURPOSE: To evaluate current practice patterns in diagnostic screening for
      asymptomatic metastatic uveal melanoma. DESIGN: Survey. PARTICIPANTS: Ocular
      oncologists practicing in North America (United States, Canada) and Europe.
      METHODS: Questionnaire sent to specialists participating in the Collaborative
      Ocular Melanoma Study (COMS) or listed in the Ophthalmic Oncology Task Force of
      the European Organization for Research and Treatment of Cancer. MAIN OUTCOME
      MEASURES: Methods used to screen patients with uveal melanoma for asymptomatic
      metastasis at initial presentation and follow-up. RESULTS: Thirty-six of 43 (84%)
      North American (COMS) specialists and 57 of 103 (55%) European specialists
      responded to the survey. At presentation, 6 of 36 (17%) North American
      specialists, versus 54 of 57 (95%) European specialists, performed at least one
      type of liver imaging study (computed tomography, magnetic resonance imaging,
      ultrasonography, or nuclear medicine) (P<0.0001). On follow-up, only 1 of 36 (3%)
      North American specialists, versus 45 of 57 (79%) European specialists, obtained
      a liver imaging study (P<0.0001). Thirty-six of 36 (100%) North American
      specialists, versus 49 of 57 (86%) European specialists, ordered chest x-rays at
      presentation (P<0.02). This disparity was greater at the time of follow-up, when
      28 of 36 (78%) North American specialists, versus 28 of 57 (49%) European
      specialists, ordered chest x-rays (P<0.01). Similar proportions of specialists in
      North America and Europe obtained a physical examination and liver function tests
      at the time of presentation and on subsequent follow-up examination. CONCLUSIONS:
      Significant differences exist between ocular oncologists in North America and
      Europe in the use of techniques to screen for metastatic uveal melanoma. North
      American COMS centers rely primarily upon liver function tests and chest x-rays.
      The majority of European centers use liver ultrasonography at initial diagnosis
      and continue to do so every 6 months. Cost-effective screening protocols for
      patients with uveal melanoma should be designed and implemented uniformly among
      ocular oncologists.

PMID- 15582083
TI  - Depression and the 25-item National Eye Institute Visual Function Questionnaire
      in older adults.
AB  - PURPOSE: To examine the impact of depression in older adults on responses to the
      25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25)
      independent of demographics, vision, and general health. DESIGN: Cross-sectional.
      PARTICIPANTS: We took the opportunity of an ongoing study on older drivers to
      address the specific aim stated above. The recruitment population consisted of
      6342 older adults (> or =60 years) who were licensed drivers residing in
      Birmingham, Alabama; who had been involved in a crash in the prior year, as
      identified by Alabama Department of Public Safety records; and whose phone
      numbers could be located. Additional eligibility criteria were visual acuity
      impairment, slowed visual processing speed, or both, and a Mini-Mental State
      Examination score of > or =23. Persons in the recruitment population who met
      these eligibility criteria and agreed to enroll in a study on driver safety
      (purpose of the main study) numbered 403. METHODS: The following questionnaires
      were interviewer administered in person and scored per standard procedures: the
      NEI VFQ-25, the Center for Epidemiological Studies Depression Scale (CES-D), a
      general health questionnaire, and a review of demographic information. Depressed
      persons were defined as those with CES-D scores of > or =16. There were complete
      data on 397 persons. MAIN OUTCOME MEASURE: Reduced score on the NEI VFQ-25
      (defined by a score of <87.5) on the total questionnaire and 12 subscales.
      RESULTS: After adjusting for demographics, vision, mental status, and general
      health, depression was significantly associated with a reduced NEI VFQ-25 score
      for total score and the subscales of distance vision, peripheral vision, role
      difficulties, dependencies, and mental health. Odds ratio point estimates in
      these adjusted associations ranged from 2.9 to 4.6. CONCLUSIONS: The results
      imply that older persons who are depressed may have reduced scores on the NEI VFQ
      25 independent of the impact of vision problems. Depression in the elderly could
      be influencing their self-perception of the burden of eye disease and treatment
      effectiveness in clinical and epidemiologic studies.

PMID- 15582084
TI  - Fixation stability using central and pericentral fixation targets in patients
      with age-related macular degeneration.
AB  - PURPOSE: To determine fixation stability for central and pericentral fixation
      targets in patients with age-related macular degeneration (AMD). DESIGN:
      Comparative study. PARTICIPANTS: Twelve patients having late-stage AMD involving
      the fovea and 10 age-matched controls having no other eye diseases and visual
      acuity better than 20/25. METHODS: Six different fixation targets (1 degrees
      cross; 1 degrees filled circle; 1 degrees letter x; small 4-point diamond; large
      4-point diamond using dimensions as in a field analyzer; large-crossover whole
      image diagonal with open 1 degrees center) were presented on a high-resolution
      monitor. Before examination, subjects were given verbal instructions to move
      their eye to see the center of the target best. Fixation stability was measured
      for the preferred eye, with the fellow eye occluded, using a gaze tracker.
      Fixation stability was quantified by calculating the bivariate contour ellipse
      area (BCEA) over 30 seconds for each target. For statistical analysis, BCEA
      values (minutes of arc2) were converted into their logarithms. The absolute
      retinal scotoma for the study eye was determined using a scanning laser
      ophthalmoscope. MAIN OUTCOME MEASURE: Bivariate contour ellipse area. RESULTS:
      Visual acuity in patients (age range, 57-87 years) ranged from 20/32 to 20/600.
      The lowest BCEA values were found for the 1 degrees letter x in patients (mean,
      12052.2%+/-254.0%) and for the 1 degrees cross in normal subjects (mean,
      1286.9%+/-47.8%); the highest BCEA values were found for the small 4-point
      diamond in patients (mean, 23109.5%+/-298.3%) and for the large 4-point diamond
      in normals (age range, 62-79 years) (mean, 3229.2%+/-105.4%). The difference
      between the targets was significant for normal subjects (analysis of variance
      [ANOVA], P<0.01) but not for patients (ANOVA, P>0.05). In normals, BCEA values
      were significantly lower for central fixation targets than for pericentral
      fixation targets (P<0.01). CONCLUSION: Fixation is significantly less stable for
      pericentral fixation targets in normal subjects, indicating an advantage for
      central fixation targets. These results are particularly significant for any
      clinical and experimental testing method that requires the patient to maintain
      stable fixation.

PMID- 15582085
TI  - Visual outcomes after lens-sparing vitrectomy for stage 4A retinopathy of
      prematurity.
AB  - PURPOSE: To assess the visual outcomes of patients with stage 4A retinal
      detachments (RDs) from retinopathy of prematurity (ROP). DESIGN: Retrospective
      review of a consecutive case series of children referred to the pediatric retina
      service of Associated Retinal Consultants, Royal Oak, Michigan. PARTICIPANTS:
      Forty-five eyes of 39 children. METHODS: The stage of RD for each patient was
      determined during an examination under anesthesia. All patients underwent a lens
      sparing pars plana vitrectomy (PPV) with membrane peeling. Postoperative anatomic
      status was determined by ophthalmoscopy either during an office examination or
      during an examination under anesthesia. Visual outcomes were ascertained by
      consulting pediatric ophthalmologists using either Teller or Allen acuities. MAIN
      OUTCOME MEASURES: Anatomic and visual outcomes. RESULTS: Formalized visual acuity
      (VA) measurement was performed in 23 eyes of 20 children, and was not performed
      in 22 eyes of 19 children. All 23 eyes that were formally tested had successful
      retinal reattachment. The macula appeared to be normal and without distortion in
      19 of 23 eyes (83%) during the follow-up period. Average logarithm of the minimum
      angle of resolution VA was 20/58. Three eyes had acuities of 20/200, and 4 had
      acuities of 20/100. All other eyes were 20/80 or better. Average age at time of
      VA was 3.51 years. CONCLUSIONS: Patients with ROP and stage 4A RDs can be treated
      successfully with respect to anatomic and visual outcome utilizing lens-sparing
      PPV.

PMID- 15582086
TI  - Lens-sparing vitrectomy for stage 4 retinopathy of prematurity.
AB  - PURPOSE: To investigate the anatomic results of lens-sparing vitrectomy for
      tractional stage 4 retinopathy of prematurity (ROP). DESIGN: Retrospective,
      noncomparative consecutive case series. PARTICIPANTS: Thirty-seven eyes (24
      patients) with tractional stage 4 ROP. INTERVENTION: Lens-sparing vitrectomy.
      MAIN OUTCOME MEASURE: Anatomic status of the retina. RESULTS: Twenty-five eyes
      had stage 4A ROP, and 12 eyes had stage 4B ROP. With a median follow-up of 13
      months (range, 6-27), 32 of 37 eyes (86%) had complete reattachment of the
      retina. Among eyes with 4A ROP, 21 of 25 eyes (84%) had complete retinal
      reattachment. Among eyes with 4B ROP, 11 of 12 eyes (92%) had complete retinal
      reattachment. At last follow-up, 29 of 37 eyes (78%) were able to fix and follow.
      CONCLUSIONS: These results indicate that lens-sparing vitrectomy is effective for
      achieving retinal reattachment in tractional stage 4 ROP. This article contains
      additional online-only material available at .

PMID- 15582087
TI  - Optical coherence tomography detects characteristic retinal nerve fiber layer
      thickness corresponding to band atrophy of the optic discs.
AB  - OBJECTIVES: To analyze retinal nerve fiber layer (RNFL) thickness in eyes with
      band atrophy by use of optical coherence tomography (OCT) and to evaluate the
      ability of OCT to detect this characteristic pattern of RNFL loss. DESIGN: Cross
      sectional, retrospective study. PARTICIPANTS: Thirty-four eyes of 18 patients
      with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors
      were studied. All eyes were divided into 3 groups according to visual field loss
      grading after Goldmann perimetry. INTERVENTIONS: Retinal nerve fiber layer
      thickness measurements with OCT. MAIN OUTCOME MEASURES: Retinal nerve fiber layer
      thickness around the optic disc was measured by OCT (3.4-mm diameter circle).
      Calculation of the changes in OCT parameters, including the horizontal (nasal +
      temporal quadrant RNFL thickness) and vertical values (superior + inferior
      quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison
      between the 3 visual field grading groups was done with the analysis of variance
      test. The receiver operating characteristic (ROC) curve for the horizontal and
      vertical value were calculated, and the areas under the curve (AUC) were
      compared. RESULTS: Retinal nerve fiber layer thickness in eyes with band atrophy
      decreased in all OCT parameters. The reduction rate in average and temporal RNFL
      thickness and horizontal value was correlated with visual field grading. The AUC
      of horizontal value was 0.970+/-0.011, which was significantly different from AUC
      of vertical value (0.903+/-0.022). CONCLUSIONS: The degree of RNFL thickness
      reduction correlated with that of visual field defects. Optical coherence
      tomography was able to identify the characteristic pattern of RNFL loss in these
      eyes.

PMID- 15582088
TI  - Percutaneous carotid artery angioplasty and stenting for ocular ischemic
      syndrome.
AB  - PURPOSE: To describe percutaneous carotid angioplasty and stenting to treat
      ocular ischemic syndrome resulting from severe intracranial carotid artery
      stenosis. DESIGN: Retrospective case series of 3 patients with ocular ischemic
      syndrome and intracranial carotid artery stenosis. INTERVENTION: All patients
      underwent carotid artery evaluation, including ultrasound, transcranial Doppler,
      magnetic resonance imaging or magnetic resonance angiography,and angiography.
      Carotid angioplasty and stenting was performed in all patients. MAIN OUTCOME
      MEASURES: Carotid angiography, fluorescein angiography, and transcranial Doppler
      imaging were used to evaluate cerebral and ocular perfusion. RESULTS: Cerebral
      perfusion improved in all patients. Fluorescein angiography arteriovenous transit
      times improved in 2 patients. One patient had a correction in the reversal of
      flow through the ophthalmic artery. Visual acuity remained stable or improved in
      all patients. There were no complications associated with the procedure.
      CONCLUSIONS: Intracranial carotid artery stenosis is a rare cause of ocular
      ischemic syndrome. With the advent of carotid angioplasty and stenting, stenotic
      lesions previously not amenable to carotid endarterectomy are now treatable with
      stenting. A complete work-up of the carotid artery is necessary in all cases of
      ocular ischemic syndrome to ensure evaluation of the entire carotid artery
      system. Early diagnosis of intracranial carotid stenosis is important for
      preservation of visual function and reducing risk of cerebral vascular event.

PMID- 15582089
TI  - A nationwide Danish study of 1027 cases of congenital/infantile cataracts:
      etiological and clinical classifications.
AB  - OBJECTIVE: To study the distribution of congenital/infantile cataract in the
      entire population of Denmark according to etiological and clinical
      classifications. DESIGN: Population-based cohort study with retrospective chart
      review. PARTICIPANTS: All children (0 to 17 years old) who were born between 1959
      and 2001 and registered with congenital/infantile cataract in Denmark during the
      period 1977 to 2001. Cases were ascertained from the mandatory Danish National
      Register of Patients, and all medical records were reviewed. METHODS: Etiological
      and clinical classifications of the cataract cases were based on information from
      the medical records. MAIN OUTCOME MEASURES: Classification of
      congenital/infantile cataract according to presumed etiology; gender; clinical
      appearance, including laterality and morphology; and the time trends according to
      etiology and laterality. RESULTS: A total of 1027 children with
      congenital/infantile cataract, 529 boys and 498 girls, were included, of whom 64%
      were bilateral. Males predominated with bilateral cataract, whereas females
      predominated with unilateral cases. Isolated cataract was the most frequent
      clinical presentation (71% of all cases), followed by an even proportion of
      cataract associated with additional ocular dysmorphology and cataract associated
      with systemic anomalies. Almost two thirds of all cases had an unknown etiology
      (idiopathic). Idiopathic cases showed a higher proportion of unilateral cataract
      and of additional ocular dysmorphology compared with cases of known etiology. The
      etiology was unknown in 87% of unilateral cases and in 50% of bilateral cases.
      The distribution by presumed etiology was stable during the study period, except
      for cataract caused by maternal infections, which decreased mainly due to the
      elimination of congenital rubella. CONCLUSIONS: With the exception of the decline
      of congenital rubella, the proportion of congenital/infantile cataract cases of
      unknown, genetic, and infectious origins has been stable since the late 1970s.
      The causes of 87% of unilateral cataracts and 50% of bilateral
      congenital/infantile cataracts remain unknown, making the prevention of the
      disease a continuing challenge.

PMID- 15582090
TI  - Ocular complications of pediatric uveitis.
AB  - PURPOSE: To determine the cumulative proportion and the visual significance of
      ocular complications of pediatric uveitis. DESIGN: Cohort study. PARTICIPANTS:
      Patients with onset of endogenous or infectious uveitis before or at age 16
      years. METHODS: Retrospective review of existing records at a university-based
      uveitis clinic. MAIN OUTCOME MEASURES: Type and prevalence of complications
      related to uveitis, time to development of complications, and vision loss after
      initial diagnosis. RESULTS: There were 148 patients, 71 males and 77 females,
      with a mean age of 10.4+/-4.9 years (median, 10.3 years) for an estimated
      prevalence of pediatric uveitis of 13.8%. Noninfectious uveitis was present in
      112 patients (75.7%); 105 (71%) patients had bilateral disease. Anterior uveitis
      accounted for 30.4%, intermediate uveitis for 27.7%, posterior uveitis for 23.7%,
      and panuveitis for 18.2% of patients. Patients were followed for a mean of 71.7
      months (range, 0 months-44 years) after diagnosis. Approximately 34% of all
      patients had 1 or more complications at the time of first diagnosis of uveitis by
      an ophthalmologist, increasing to 61.6% by 3 months, 69.4% by 6 months, 75.2% by
      1 year, and 86.3% by 3 years after diagnosis. There were a total of 617
      complications of all types. Anterior and intermediate uveitis had a higher risk
      of band keratopathy (P = 0.005). Posterior and intermediate uveitis had a lower
      risk of cataract (P = 0.009) or posterior synechiae (P<0.001). Intermediate
      uveitis had a higher risk of cystoid macular edema compared with anterior or
      posterior uveitis (P = 0.002). The cumulative percentages (standard error) of
      patients with first loss to 20/200 or worse after diagnosis in the affected eyes
      of unilateral cases or in either eye of the bilateral cases were: 31.3% (3.9) at
      1 month; 40.5% (4.1) at 6 months; 56.0% (4.3) at 24 months; and 69.6% (4.5) at 60
      months. Fifty-four patients (48.2%) received systemic antiinflammatory or
      immunomodulatory therapy. Sixty-eight patients (45.9%) had ocular surgery, and 38
      of these had ocular surgery in both eyes. CONCLUSIONS: Childhood uveitis is
      significant for numerous complications, many of which are vision threatening.
      Complications increase with duration of disease.

PMID- 15582091
TI  - Visual impairment in children born at full term from 1972 through 1989 in
      Finland.
AB  - OBJECTIVE: To investigate the incidence, prevalence, and causes of visual
      impairment in children born at full term and to determine conditions and factors
      associated with visual impairment. DESIGN: Retrospective, cross-sectional,
      population-based study. PARTICIPANTS: All visually impaired individuals from 0 to
      17 years of age who were born at full term from 1972 through 1989 in Finland and
      recorded in the Finnish Register of Visual Impairment (n = 556) were eligible for
      this study. METHODS: Data in the Finnish Register of Visual Impairment relating
      to 556 subjects were supplemented with data from hospital records and other
      national registers (Register of Births, Register of Congenital Malformations,
      Finnish Care Register, and Finnish Cancer Register). Data relating to the
      children born at full term were compared with Finnish perinatal and vital
      statistics and with data concerning children born prematurely. The chi-square
      test (Mantel-Haenszel) and stepwise logistic regression analysis were used in
      statistical analysis of the data. MAIN OUTCOME MEASURES: Visual acuity, time of
      onset of visual impairment, ophthalmic diagnosis of visual impairment, systemic
      disease, multiple handicap, 5-minute Apgar score, prenatal disorders, perinatal
      disorders, disorders arising during infancy and childhood, and treatment.
      RESULTS: Four hundred thirty-one of the 556 individuals with visual impairment
      (78%) had been born at full term. Visual impairment was predominantly associated
      with genetic (53%) and prenatal (34%) factors. Ocular malformations (34%),
      retinal diseases (31%), and neuro-ophthalmologic disorders (26%) were the main
      ophthalmic diagnoses. Optic nerve atrophy (20%) and congenital cataract (13%)
      were the most common single diagnoses. The occurrence of blindness, systemic
      disease, and multiple handicap was 40%, 43%, and 45%, respectively. CONCLUSIONS:
      The incidence of visual impairment in children born at full term did not decline
      during the 2 decades covered by this study. The findings reflected the lack of
      treatment for genetic eye diseases. The results also confirmed an obvious need
      for further understanding of mechanisms underlying congenital anomalies of the
      human visual system.

PMID- 15582092
TI  - Vision in Preschoolers Study.

PMID- 15582094
TI  - Vision in Preschoolers Study.

PMID- 15582097
TI  - Uniocular drug trials.

PMID- 15582099
TI  - Anecortave acetate.

PMID- 15582101
TI  - Disseminated conjunctival melanoma.

PMID- 15582102
TI  - Further evidence for mirror-reversed laterality in lines of fish selected for
      leftward or rightward turning when facing a predator model.
AB  - In the teleost fish Girardinus falcatus eye preferences for inspecting a
      potential predator is highly heritable and this consented to select lines with
      opposed laterality. In previous studies individuals from a RD line (rightward
      turning when facing a dummy predator) and those from a LD line (leftward turning)
      were subjected to several other laterality tests (most of which, possibly all,
      were visually based). Since they obtained opposite scores in all tests, it was
      suggested that LD and RD fish have complete mirror-reversed organizations of the
      brain. Here, we studied fish from selected lines in a new set of laterality tests
      including some non-visual tests. They included measures of (1) rotational
      preference in the home tank (2) direction of spontaneous swimming in the dark (3)
      escape trajectories after delivery of an auditory stimulus (4) escape turning
      direction to a fast approaching visual stimulus. The results of the first three
      tests are congruent with the finding of previous studies in that fishes of the
      two lines showed opposite direction of lateralisation. When tested for laterality
      in the escape response to a fast approaching stimulus, fish of the LD and RD
      lines showed no differences and both were biased toward leftward escape. Overall
      these results suggest the existence in G. falcatus of a single mechanism
      controlling a co-ordinate placement of the great majority of lateralised
      functions. Yet the results of the fourth test suggest that a few lateralized
      functions are controlled by different mechanisms that were unaffected by
      artificial selection.

PMID- 15582103
TI  - Dopamine agonists suppress cholinomimetic-induced tremulous jaw movements in an
      animal model of Parkinsonism: tremorolytic effects of pergolide, ropinirole and
      CY 208-243.
AB  - Considerable evidence indicates that cholinomimetic-induced tremulous jaw
      movements in rats share many characteristics with human Parkinsonian tremor, and
      several antiparkinsonian drugs suppress cholinomimetic-induced tremulous jaw
      movements. The present study investigated three different types of dopamine
      agonists, which have known antiparkinsonian characteristics, for their ability to
      suppress the tremulous jaw movements induced by tacrine (5.0 mg/kg). The non
      selective dopamine agonist pergolide, a widely used antiparkinsonian drug, was
      highly potent at suppressing tacrine-induced jaw movements (e.g. 0.125-1.0
      mg/kg). The selective D2 agonist ropinirole, which also is used clinically as an
      antiparkinsonian drug, suppressed jaw movements in the dose range of 2.5-20.0
      mg/kg. The D1 agonist CY 208-243, which has been reported to suppress tremor,
      also reduced jaw movement activity (4.0 mg/kg). Across several studies, the rank
      order of potency for suppressing cholinomimetic-induced jaw movements in rats is
      related to the potency for producing antiparkinsonian effects in humans. Together
      with previous studies, the present results suggest that cholinomimetic-induced
      jaw movements in rats can be used to characterize dopaminergic antiparkinsonian
      agents and to investigate the basal ganglia circuits involved in the generation
      of tremulous movements.

PMID- 15582104
TI  - Behavioural sensitisation following repeated intermittent oral administration of
      Catha edulis in rats.
AB  - A prolonged use of psychostimulants has been suggested to induce long-lasting
      behavioural sensitisation which plays a role in the acquisition and maintenance
      of addictive behaviour. A study was conducted to evaluate the effect of repeated
      oral administration of Catha edulis in rats. Male Sprague-Dawley rats divided
      into five groups received: saline, S-(-)-cathinone (1.5 mg/kg), D-(+)-amphetamine
      (1.5 mg/kg) and standardized C. edulis extract (50 or 200 mg/kg) once daily for
      nine consecutive days and later challenged with the same psychostimulants after
      five abstinence days. Then, 2 weeks later, rats were decapitated and the level of
      neurotransmitters were assessed. Behavioural activities were monitored using
      activity and sniffing boxes. The results demonstrated that the three
      psychostimulants induced strong behavioural sensitisation in rats. Whereas,
      neurotransmitters analyses showed no significant changes in the basal level of
      dopamine in most of the regions except that C. edulis extract (200 mg/kg)
      significantly reduced the level of DA, DOPAC and HVA in the anterior caudate
      putamen (P < 0.05). The capacity of C. edulis to elicit a long-lasting
      behavioural sensitisation support the anecdotal literatures about psychiatric
      problems associated with C. edulis chewing.

PMID- 15582105
TI  - The role of dopamine in cognitive sequence learning: evidence from Parkinson's
      disease.
AB  - Electrophysiological and computational studies suggest that nigro-striatal
      dopamine may play an important role in learning about sequences of
      environmentally important stimuli, particularly when this learning is based upon
      step-by-step associations between stimuli, such as in second-order conditioning.
      If so, one would predict that disruption of the midbrain dopamine system--such as
      occurs in Parkinson's disease--may lead to deficits on tasks that rely upon such
      learning processes. This hypothesis was tested using a "chaining" task, in which
      each additional link in a sequence of stimuli leading to reward is trained step
      by-step, until a full sequence is learned. We further examined how medication (L
      dopa) affects this type of learning. As predicted, we found that Parkinson's
      patients tested 'off' L-dopa performed as well as controls during the first phase
      of this task, when required to learn a simple stimulus-response association, but
      were impaired at learning the full sequence of stimuli. In contrast, we found
      that Parkinson's patients tested 'on' L-dopa performed better than those tested
      'off', and no worse than controls, on all phases of the task. These findings
      suggest that the loss of dopamine that occurs in Parkinson's disease can lead to
      specific learning impairments that are predicted by electrophysiological and
      computational studies, and that enhancing dopamine levels with L-dopa alleviates
      this deficit. This last result raises questions regarding the mechanisms by which
      midbrain dopamine modulates learning in Parkinson's disease, and how L-dopa
      affects these processes.

PMID- 15582106
TI  - An intermittent, controlled-rate, slow progressive degeneration model of
      Parkinson's disease: antiparkinson effects of Sinemet and protective effects of
      methylphenidate.
AB  - The causes of nigrostriatal neuron degeneration in Parkinson's disease (PD) are
      not known, but it has been suggested that exogenous or endogenous factors or
      neurotoxins may play a role. The degree of vulnerability to neurotoxins or other
      potential mediators of nigral dopamine cell death is thought to be important in
      understanding Parkinson's disease. In most animal models, the rate of terminal
      degeneration and corresponding functional impairment is too rapid to investigate
      effectively either cell vulnerability or the potential benefits of some
      neuroprotective treatments. In the present study, a new model of Parkinson's
      disease is described that might help in addressing the issue of nigral cell
      vulnerability and to evaluate interventions with clinical potential. 6
      Hydroxydopamine (6-OHDA) was infused in escalating, intrastriatal doses over
      several weeks. Control animals received multiple infusions of vehicle at the same
      volume. Behavioral testing was carried out between each infusion, including
      forelimb-use and somatosensory function. A symptomatic threshold was established
      for each animal, indicating the amount of neurotoxin required to induce a stable
      deficit. Oral administration of L-DOPA (Sinemet) ameliorated limb-use asymmetries
      acutely. An immunocytochemical assay for tyrosine hydroxylase, a dopamine cell
      marker, revealed a partial loss of immunoreactive cells in the substantia nigra.
      Animals that were co-administered methylphenidate (MPH), a dopamine transport
      inhibitor, along with the 6-OHDA were spared from the behavioral and
      neurochemical effects of 6-OHDA, despite receiving more than twice as much
      neurotoxin as controls. These data suggest that establishing a symptomatic
      threshold preclinically may help researchers evaluate potential treatments and
      model individual and group resistance to nigrostriatal insults.

PMID- 15582107
TI  - Effects of ibotenic acid lesions of the mediodorsal thalamus on memory:
      relationship with emotional processes in mice.
AB  - The effects of ibotenic acid lesions of the mediodorsal nucleus of the thalamus
      (MD) on memory and fear reactivity in mice were studied. In the first experiment,
      MD subjects were submitted to a behavioral design allowing to study the
      relationship between memory and anxiety [Krazem A, Borde N, Beracochea D. Effects
      of diazepam and beta-CCM on working memory in mice: relationship with emotional
      reactivity. Pharmacol Biochem Behav 2001;68:235-44; Beracochea D, Krazem A,
      Jaffard R. Methyl beta carboline-3-carboxylate reverses the working memory
      deficits induced either by chronic alcohol consumption or mammillary body lesions
      in mice. Psychobiology 1995;23:52-8]. In a second experiment, MD-lesioned
      subjects were submitted to a GO/NOGO temporal alternation task involving two
      intertrial intervals (ITIs: 0 and 30 s). Lesioned subjects exhibited large
      bilateral mediodorsal thalamic lesions with small damage into the centromedial
      thalamic nucleus. In the first experiment, MD-lesioned animals performed normally
      a sequential alternation task involving fixed ITIs over seven successive trials
      (5 or 30 s); in contrast, MD-lesioned subjects exhibited deficits in the
      sequential task involving the same but mixed ITIs (30-5 s versus 5-30 s) the
      deficit being observed for the last trials of the series, regardless the ITIs
      used. MD lesions increased fear reactivity in an elevated-plus maze, and scores
      of anxiety were negatively correlated with performance in the mixed alternation
      schedule. The second experiment involving non spatial information extended
      results of the first experiment in showing that the deficit of MD-lesioned
      animals was not dependent on the ITIs separating trials. Overall, our data show
      that MD-lesioned subjects exhibit a cognitive impairment characterized by a
      difficulty to maintain an alternation rule in situations involving procedural
      variance, and this deficit could stem primarily from an increase of fear
      reactivity.

PMID- 15582108
TI  - Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice
      as a model of Alzheimer's disease.
AB  - Transgenic mouse models of Alzheimer's disease (AD) have been recently advanced.
      Tg2576 mice have been shown to develop progressive beta-amyloid (Abeta) neuritic
      plaques and exhibit impairment of cognitive function. The aim of this study was a
      better characterization of different aspects of spatial memory performance of
      transgenic mice, observed at a time when levels of soluble Abeta are elevated and
      Abeta neuritc plaques start to appear. A general elevation of basal locomotory
      activity in the home cage was found in Tg2576 mice, which also exhibited an
      impairment of spontaneous alternation in the Y-maze test. Tg2576 mice were not
      flexible upon changes in the schedule and failed to codify spatially the testing
      environment. Consistently, a deficit of spatial memory was also observed when
      mice were assessed for levels of reactivity to spatial change in the modified
      open-field test with objects. Compared to controls, Tg2576 mice also exhibited an
      increased number of explorative approaches to the different objects, and failed
      to discriminate the displacement of the object. Consistently with the hypothesis
      of increased disinhibition, a differential behavioural response to the plus-maze
      paradigm was exhibited by Tg2576 mice. Results clearly indicate that Tg2576 mice
      are characterized by a number of specific behavioral cognitive alterations,
      compatible with Alzheimer's disease (AD), which make them a suitable animal model
      for testing of novel anti-AD drugs.

PMID- 15582109
TI  - Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding
      effects of morphine, methamphetamine and cocaine in mice.
AB  - There is a body of evidence implying the involvement of the glutamatergic system
      in the conditioned rewarding effects of drugs of abuse. It is recognized that the
      release of extracellular glutamate from nerve terminals is counterbalanced by the
      functions of neuronal and glial glutamate transporters. In the present study, we
      investigated the effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153),
      a glutamate transporter activator, on the induction of the conditioned place
      preference to morphine, methamphetamine and cocaine in mice. In the conditioned
      place preference paradigm, mice were conditioned with repeated subcutaneous
      injections of morphine (5 mg/kg), methamphetamine (2 mg/kg) or cocaine (8 mg/kg)
      in combination with or without MS-153 (3 and 10 mg/kg). Co-administration of MS
      153 at a dose of 10 mg/kg, but not 3 mg/kg, significantly attenuated the
      induction of conditioned place preference to morphine, methamphetamine and
      cocaine. However, MS-153 itself produced neither conditioned place preference nor
      aversion. On the other hand, co-administration of MS-153 (10 mg/kg) did not alter
      the acute locomotor activation elicited by a single injection of morphine,
      methamphetamine and cocaine. These results suggest that MS-153, a glutamate
      transporter activator, has an inhibitory effect on the conditioned rewarding
      effects of morphine, methamphetamine and cocaine without affecting their acute
      locomotor responses.

PMID- 15582110
TI  - Hippocampal lesions, species-typical behaviours and anxiety in mice.
AB  - The hippocampus is believed to play an important role in spatial cognition and
      anxiety. Much of the supporting evidence is derived from rat studies. Recent
      reports on hippocampal lesioned mice also showed impairments in spatial function,
      but anxiety was not uniformly diminished. There were, however, striking
      impairments in several "species typical" behaviours; lesioned mice made poorer
      nests, and hoarded and burrowed less. In the present experiments, mice with
      excitotoxic hippocampal lesions were tested in a well-established anxiety
      paradigm, the light-dark box. As in previous anxiety tests, the results were
      mixed; some measures (reduced dark time) suggested lesioned mice were less
      anxious; others (fewer light-dark transits) suggested greater anxiety. However,
      lesioned mice only made fewer transits when the door was small. This suggested
      that the tendency to enter small holes, so characteristic of small rodents, was
      reduced; subsequent tests showed lesioned mice preferred to explore in an alley
      rather than enter its attached tunnels. Further tests of "species typical"
      behaviours revealed that lesioned mice spent less time digging and climbing, and
      made less use of cardboard shelters in their cages. This was not due to
      inactivity; lesions did not reduce grooming or locomotion. Finally, tests of
      hyponeophagia showed hippocampal lesions reduced this measure of anxiety, so long
      as the control baseline was sufficiently high. Overall, the results suggest that
      the hippocampus is important in many species-typical behaviours, potentially
      influencing performance in a range of behavioural tests. However, species-typical
      behaviours offer easy and economical ways to test for hippocampal dysfunction,
      for example, in genetically modified mice.

PMID- 15582111
TI  - Prenatal exposure to a repeated variable stress paradigm elicits behavioral and
      neuroendocrinological changes in the adult offspring: potential relevance to
      schizophrenia.
AB  - Exposure to stress during gestation induces marked changes in the behavior of the
      affected offspring. Examining the consequences of prenatal stress may prove
      useful in understanding more about the origins of schizophrenia because a number
      of clinical investigations have suggested that developmental insults are
      associated with an increased incidence of schizophrenia. The purpose of these
      studies is to investigate the effects of stress during gestation on the behaviors
      of the adult male rat offspring with an emphasis on developing a heuristic animal
      model of schizophrenia. Pregnant female Sprague-Dawley rats were exposed to a
      novel variable stress paradigm during either the second or third week of
      gestation. Behavioral and neuroendocrinological consequences of prenatal stress
      exposure were evaluated in the male offspring on postnatal day 35 or 56. Prenatal
      stress exposure during the third week of pregnancy caused adult male rats to
      exhibit prolonged elevation in plasma glucocorticoid levels following acute
      exposure to restraint stress indicative of diminished glucocorticoid negative
      feedback. Similarly, exposure to stress during the third week of pregnancy
      elicited an enhanced locomotor response to the psychomotor stimulant amphetamine
      on postnatal day 56 but not on postnatal day 35. In addition, prepulse inhibition
      of the acoustic startle response was diminished across a range of prepulse
      stimulus intensities in prenatally stressed adult male rats. Similarly,
      prenatally stressed rats showed evidence of a disruption in auditory sensory
      gating as measured by the N40 response. Taken together, these findings suggest
      that prenatal stress exposure significantly changed many facets of adult rat
      behavior. Interestingly, the behaviors that are altered have been used to
      validate animal models of schizophrenia and therefore, suggest that this
      preparation may be useful to learn more about some aspects of the pathophysiology
      of schizophrenia.

PMID- 15582112
TI  - The effect of intrahippocampal injection of testosterone enanthate (an androgen
      receptor agonist) and anisomycin (protein synthesis inhibitor) on spatial
      learning and memory in adult, male rats.
AB  - In most mammals, the hippocampus has a well-documented role in spatial memory
      acquisition. High concentration of androgen receptors in fundamental centers of
      learning and memory in brain such as hippocampus shows that there may be some
      relationships between androgen receptors and cognitive aspects of brain. Previous
      studies, which have shown sex-dependent differences in hippocampal morphology and
      physiology, suggest a modulatory role for sex steroids in hippocampal function.
      Androgens have been shown to modulate some hippocampal-mediated behaviors
      including learning and memory. To study the mechanism of action of androgens in
      processes underlying learning and memory, anisomycin, a protein synthesis
      inhibitor was used to prevent the genomic effects of testosterone. Therefore, the
      effects of anisomycin and testosterone together were assessed on rat's
      performance in MWM. Rats received anisomycin (2.5 microg/0.5 microl),
      testosterone (80 microg/0.5 microl) or both anisomycin (2.5 microg/0.5 microl)
      and testosterone (80 microg/0.5 microl) through the connulas in the CA1 region.
      Anisomycin was injected 20 min and testosterone was injected 35 min before
      training each day. The results showed that anisomycin (2.5 microg/0.5 microl) and
      testosterone (80 microg/0.5 microl) increased latencies to find the invisible
      platform. But the group that received testosterone and anisomycin together was
      decrease in latency and traveled distance to find the invisible platform.

PMID- 15582113
TI  - Spatial discrimination deficits by excitotoxic lesions in the Morris water escape
      task.
AB  - The effects of the cholinesterase inhibitors (ChEI) metrifonate and donepezil
      were assessed on spatial performance of rats with bilateral lesions of the
      entorhinal cortex (EC), which is thought to model early changes in the brains of
      patients suffering from Alzheimer's disease. In the present study, we found that
      spatial discrimination deficits in rats, induced by bilateral ibotenic acid (IBO)
      lesions of the EC region can partially be antagonised by treatment with the
      cholinesterase inhibitors metrifonate (30 mg kg(-1)) and donepezil (0.3 and 3 mg
      kg(-1)). Performance was improved in the spatial discrimination task compared
      with that of the EC-lesioned control group. It is concluded that the rat with
      bilateral EC lesions is a suitable deficit model for the assessment of effects of
      putative Alzheimer therapeutics.

PMID- 15582114
TI  - Disruption of learned irrelevance in acute schizophrenia in a novel continuous
      within-subject paradigm suitable for fMRI.
AB  - Learned irrelevance (LIrr) is closely related to latent inhibition (LI). In LI a
      to-be-conditioned stimulus (CS) is prexposed alone prior to the opportunity to
      learn an association between the CS and an unconditioned stimulus (UCS). In LIrr
      preexposure consists of intermixed presentations of both CS and UCS in a random
      relationship to each other. In both paradigms preexposure leads in normal
      subjects to reduced or retarded learning of the CS-UCS association. Acute
      schizophrenics fail to show LI. LI is usually demonstrated as a one-off, between
      groups difference in trials to learning, so posing problems for neuroimaging. We
      have developed a novel, continuous, within-subject paradigm in which normal
      subjects show robust and repeated LIrr. We show that this paradigm is suitable
      for functional magnetic resonance imaging (fMRI) and gives rise, in normal
      subjects, to activation in the hippocampal formation, consistent with data from
      animal experiments on LI. We also report, consistent with previous studies of LI,
      loss (indeed, significant reversal) of LIrr in acute (first 2 weeks of current
      psychotic episode) schizophrenics. Chronic schizophrenics failed to demonstrate
      learning, precluding measurement in this group of LIrr. These findings establish
      the likely value of the new paradigm for neuroimaging studies of attentional
      dysfunction in acute schizophrenia.

PMID- 15582115
TI  - Isolation stress during the third postnatal week alters radial arm maze
      performance and corticosterone levels in adulthood.
AB  - Stressful experiences during development cause long-lasting changes in
      neuroendocrine systems as well as lasting changes in behavior. The present study
      examines the long-term consequences of daily periods of social isolation during
      the third postnatal week on radial arm maze performance in adulthood. Male rat
      pups were either isolated for 6 h per day between postnatal days 15-21 or
      remained in the home cage. This manipulation caused a significant increase in
      plasma corticosterone during the isolation period. As adults, these animals were
      tested on a 12-arm radial arm maze. Rats that experienced social isolation during
      development made more working memory errors during initial acquisition but
      reached an asymptotic level of performance comparable to controls. The pattern of
      reference memory errors across testing was comparable to the pattern of working
      memory errors, though the difference between isolated and control animals was not
      significant. Blood samples taken in adulthood revealed that social isolation
      during development results in an long-term elevation in plasma corticosterone
      levels. These findings indicate that isolation stress during the third week of
      life leads to lasting impairments in cognition and HPA axis activity and suggest
      a potential alteration in hippocampal function.

PMID- 15582116
TI  - Early deprivation under specific conditions leads to reduced interest in reward
      in adulthood in Wistar rats.
AB  - Early life adversity can lead to increased vulnerability to psychiatric disease
      including depression, with symptoms of depressed mood, impaired coping with
      negative events, anhedonia, reduced appetite, and elevated stress hormone
      activity. In rats, postnatal manipulation studies have focused on behavioural and
      endocrine anxiety effects, and have demonstrated that mild pup stimulation in the
      form of early handling (EH) is chronically anxiolytic relative to no stimulation
      in the form of non-handling (NH). Furthermore, apparently severe manipulations in
      the form of 3-4 h daily litter-dam separation (maternal separation) or pup-litter
      dam separation (early deprivation, ED) are either without effect or even EH-like,
      relative to NH. In this Wistar rat study, we investigated the effects of ED under
      different circadian and thermal conditions on adulthood behavioural and endocrine
      responsiveness to environmental challenge, relative to NH. ED was performed on
      days 1-14, during either the Light or Dark phase and at either 21 degrees C
      (cold) or 32 degrees C (warm). Dark-cold ED adults exhibited reduced motivation
      to obtain sucrose in a progressive ratio schedule, tended to be less mobile in a
      forced swim test, but did not exhibit an escape deficit in a foot-shock pre
      exposure/shuttle box test, or altered basal or stress endocrine activity. Light
      ED was completely without effect on adult phenotype. Even relative to stringent
      NH comparison, dark-cold ED leads to a long-term trait of mild gustatory
      anhedonia in Wistar rats.

PMID- 15582117
TI  - Early social and physical deprivation leads to reduced social motivation in
      adulthood in Wistar rats.
AB  - Behavioural abnormalities in adulthood may have their origin in a disturbed
      interaction with the environment during postnatal development. We tested the
      consequences for adult social motivation of early deprivation (ED) of rat pups
      from mothers and littermates relative to nonhandled (NH) pups. Early deprivation
      was performed at room or warm ambient temperatures, cold-ED and warm-ED,
      respectively, and during either the dark or light phase of the daily cycle. In
      adulthood, rats that were unrelated and unfamiliar but of the same treatment
      group were introduced in pairs to an open field for a 30-min test. Social
      behaviour in home base and exploration modes was assessed using algorithmic
      analysis of the XY locations of the two rats. Findings revealed that Cold-ED
      induced a preference for a separate home base, which limited significantly the
      episodes of social interactions, in comparison to NH. Warm-ED had no comparable
      effect on the rats' social behaviour. These findings indicate that ED under
      ambient conditions that constitute severe thermal stress for rat pups leads to
      development of reduced social motivation in adulthood.

PMID- 15582118
TI  - Angiotensinase activity is asymmetrically distributed in the amygdala,
      hippocampus and prefrontal cortex of the rat.
AB  - There are important asymmetries in brain functions such as emotional processing
      and stress response in humans and animals. Knowledge of the bilateral
      distribution of brain neurotransmitters is important to appropriately understand
      its functions. Some peptides such as those included in the renin-angiotensin
      system (RAS) and cholecystokinin (CCK) are related to modulation of behavior and
      stress. However, although angiotensin AT1 and CCK type 2 receptors were found in
      adult rat brain, there are no studies of their bilateral distribution in stress
      related areas. The function of angiotensin peptides is depending on the action of
      several aminopeptidases (AP) called angiotensinases, some of them being also
      involved in the metabolism of CCK. We have studied the bilateral distribution of
      soluble (SOL) and membrane-bound (MEM) alanyl- (AlaAP), cystinyl- (CysAP),
      glutamyl- (GluAP) and aspartyl- (AspAP) AP activities in stress-related areas
      such as amygdala, hippocampus and medial prefrontal cortex of adult male rats in
      resting conditions. These enzymes are involved in the metabolism of angiotensins
      (AlaAP, CysAP, GluAP, AspAP) and CCK (GluAP, AspAP). In the amygdala, all the
      activities studied showed a right predominance with a significant difference
      ranging from 30% for SOL CysAP to 125% for SOL GluAP. In the hippocampus, there
      was a left predominance for SOL AlaAP, SOL and MEM CysAP and MEM AspAP activities
      (100, 80, 300 and 100% higher, respectively). In contrast, GluAP predominated
      remarkably in the right hippocampus (eight-fold for SOL and three-fold for MEM).
      In the prefrontal cortex, SOL and MEM CysAP and SOL AspAP predominated in the
      left hemisphere (40, 100 and 40% higher, respectively). These results
      demonstrated a heterogeneous bilateral pattern of angiotensinase activities in
      motivation and stress-related areas. This may reflect an uneven asymmetrical
      distribution of their endogenous substrates depending on the brain location and
      consequently, it would be also a reflect of the asymmetries in the functions they
      are involved in.

PMID- 15582119
TI  - Goodbye from Barcelona!

PMID- 15582121
TI  - Place of the liver biopsy in liver transplantation.

PMID- 15582122
TI  - The start of a new era in bile physiology.

PMID- 15582123
TI  - Processing of protein glycation, oxidation and nitrosation adducts in the liver
      and the effect of cirrhosis.
AB  - BACKGROUND/AIMS: Plasma proteins are modified non-enzymatically in vivo by
      glycation, oxidation and nitrosation processes. Hepatic extraction of albumin
      glycated in vitro was reported but it is not clear if plasma proteins glycated in
      vivo also undergo hepatic extraction. We investigated the hepatic extraction of
      glycated, oxidised and nitrosated proteins in vivo. METHODS: Protein glycation,
      oxidation and nitrosation marker residues and free adducts were determined in
      portal, hepatic and peripheral venous blood plasma of cirrhotic patients and
      hepatic and peripheral venous blood plasma (as a surrogate of portal venous
      blood) of control subjects by liquid chromatography-mass spectrometry. RESULTS:
      There was no evidence for extraction of glycated, oxidised or nitrosated proteins
      or related free adducts by the liver in control subjects. There was limited
      extraction of methylglyoxal-modified proteins in cirrhotic patients and twofold
      increases in the concentrations of fructosyl-lysine and advanced glycation
      endproduct residues of plasma protein, with respect to controls. Remarkably,
      glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as
      a consequence of hepatic lipid peroxidation. CONCLUSIONS: We found no evidence
      for hepatic extraction of glycated, oxidised and nitrosated proteins or related
      free adducts in subjects with normal liver function and limited extraction of
      methylglyoxal-modified protein in cirrhotic subjects.

PMID- 15582124
TI  - Epidemiology of liver disease in cystic fibrosis: a longitudinal study.
AB  - BACKGROUND/AIMS: To describe the prevalence of liver disease in a cohort of 241
      cystic fibrosis (CF) patients. METHODS: 241 CF patients were followed-up every 3
      months with clinical and biological assessment, and every year with
      ultrasonography of the liver. The presence of liver disease was studied using a
      multivariate Cox's regression analysis including variables such as history of
      meconium ileus, pulmonary function, pancreatic insufficiency and CFTR gene
      mutations. RESULTS: The prevalence of liver disease was 18, 29, and 41% after 2,
      5 and 12 years, respectively, and did not increase thereafter. In multivariate
      analysis, the probability of liver disease was independently associated with
      history of meconium ileus (P = 0.001) and pancreatic insufficiency (P = 0.004).
      CFTR mutations and severity of pulmonary disease were not associated with liver
      disease. Cirrhosis occurred in 19 (7.8%) patients at a median age of 10 years,
      and liver transplantation was required in five patients. CONCLUSIONS: This study
      shows that CF related-liver disease occurs mainly in the first decade of life
      with a prevalence of 41% of patients at 12 years of age. A history of meconium
      ileus and pancreatic insufficiency are predictive of liver disease. Preventive
      treatment with ursodesoxycholic acid could be considered in patients with
      meconium ileus.

PMID- 15582125
TI  - Curcumin inhibits NF-kappaB activation and reduces the severity of experimental
      steatohepatitis in mice.
AB  - BACKGROUND/AIMS: While oxidative stress is a feature of non-alcoholic
      steatohepatitis, the causal link between oxidative stress and inflammatory
      recruitment has yet to be demonstrated. We analysed the role of NF-kappaB redox
      sensitive signalling pathway of inflammatory recruitment in experimental
      steatohepatitis. METHODS: Mice were fed the methionine and choline deficient
      (MCD) or the control diet, with or without curcumin, an NF-kappaB inhibitor, for
      up to 4 weeks. Histopathology, lipoperoxides, NF-kappaB/DNA binding and
      expression of NF-kappaB-regulated genes were assessed. RESULTS: MCD-fed mice
      developed steatohepatitis accompanied by dramatic accumulation of hepatic
      lipoperoxides, activation of NF-kappaB and induction of pro-inflammatory ICAM-1,
      COX-2, MCP-1 and CINC mRNA. Curcumin significantly reduced MCD-induced
      inflammation but had no effect on steatosis or on the level of hepatic lipid
      peroxides. Curcumin prevented the MCD-induced activation of NF-kappaB and
      decreased downstream induction of ICAM-1, COX-2 and MCP-1. However, it failed to
      reduce activation of AP-1, MAPK pathways or CINC expression. CONCLUSIONS:
      Curcumin alleviates the severity of hepatic inflammation in experimental
      steatohepatitis induced by the MCD diet, an effect likely to be mediated via
      inhibition of NF-kB activation and dependent pro-inflammatory genes. The NF
      kappaB pathway is one among several possible signalling pathways by which
      inflammation is recruited in experimental steatohepatitis.

PMID- 15582126
TI  - Evaluation of a panel of non-invasive serum markers to differentiate mild from
      moderate-to-advanced liver fibrosis in chronic hepatitis C patients.
AB  - BACKGROUND/AIMS: In chronic hepatitis C (CHC) infection, a liver biopsy provides
      important information that guides treatment decisions, but is invasive, expensive
      and associated with possible complications. Extracellular matrix remodeling
      proteins may be useful non-invasive markers of fibrosis. The aim of this study
      was to evaluate the diagnostic accuracy of a panel of these markers in CHC
      patients, develop a predictive algorithm that differentiates no/mild (METAVIR F0
      F1) from moderate/severe (F2-F4) fibrosis, and validate the model in external
      cohorts. METHODS: A combination of matrix markers were initially evaluated and
      optimized in 294 CHC patients from a single center, and validated in an external
      cohort of 402 patients. RESULTS: Hyaluronic acid, TIMP-1 and alpha2-macroglobulin
      were selected as having the best predictive accuracy for F2-F4 fibrosis (combined
      AUROC = 0.831). At an index cut-off >0.36 and prevalence for F2-F4 of 52%,
      results in all 696 patients indicated positive and negative predictive values of
      74.3 and 75.8% with an accuracy of 75%. CONCLUSIONS: The three-marker panel may
      reliably differentiate CHC patients with moderate/severe fibrosis from those with
      no/mild fibrosis, although accurate delineation between stages was not possible.
      Prospective studies are required to determine the potential utility of the marker
      panel in guiding treatment decisions and following disease progression.

PMID- 15582127
TI  - Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver
      disease.
AB  - BACKGROUND/AIMS: Data from animal models of fibrosis and fatty liver suggest that
      leptin may mediate the profibrogenic responses in the liver, but the association
      of leptin and liver fibrosis in human nonalcoholic fatty liver disease (NAFLD)
      remains undefined. We aimed at determining the relation between leptin and liver
      fibrosis in human NAFLD. METHODS: Human plasma leptin and several indicators of
      insulin resistance were measured in 88 NAFLD patients and matched controls.
      RESULTS: Leptin levels were significantly greater in patients with more advanced
      fibrosis (P = 0.005). By multivariate analysis, the significant association
      between leptin and fibrosis was abolished (adjusted P = 0.3) when controlling for
      confounders including age, gender, BMI, diabetes and insulin resistance. Only age
      (adjusted P = 0.006) and insulin sensitivity (adjusted P = 0.04) correlated
      significantly with fibrosis stage. A second liver biopsy was performed in 39 out
      of the 88 patients at 27.9 +/- 16 months. Leptin levels were not significantly
      different between patients who had fibrosis progression (n = 10) and those who
      did not (n = 29). CONCLUSIONS: In human NAFLD, no relationship between leptin
      levels and fibrosis stage was demonstrated. The correlation of leptin and
      fibrosis severity seems to be an indicator of the factors that determine leptin
      production.

PMID- 15582128
TI  - Development of a scaled up liver device incorporating cryo-preserved pig liver
      micro-organs.
AB  - BACKGROUND/AIMS: Currently there is no effective therapy for most patients with
      fulminant or end stage liver disease. METHODS: Pig liver micro-organs (LMOs),
      which preserve liver micro-architecture and ensure a maximal 150-200mum distance
      from a source of nutrients and gases have been prepared and a method to cryo
      preserve them has been developed. A new scaled-up extra-corporeal liver device
      termed aLIVE-H in which LMOs are exposed to liver-like hemodynamic conditions has
      also been developed. The purpose of this work is to test the safety and function
      of cryo-preserved LMOs and how the hemodynamic properties of the scaled up aLIVE
      device affect their function. RESULTS: Pig LMOs in aLIVE-H, transcribe albumin
      and Factor V at similar levels, irrespective of their position within the
      bioreactor, indicating that the hemodynamic features of the aLIVE-H device allow
      for homogeneous plasma distribution and proper function at different locations.
      Cryo-preserved LMOs transcribe albumin and Factor V at levels comparable to those
      transcribed by a normal pig liver. Connecting the aLIVE-H bioreactor to normal
      pigs did not affect key blood components and biochemical parameters. CONCLUSIONS:
      An extra-corporeal liver device aLIVE-H which imitates the hemodynamic and
      functional properties of the normal liver and incorporates cryo-preserved LMOs
      has been developed and characterized. aLIVE-H was found to perform key synthetic
      liver functions.

PMID- 15582129
TI  - Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury
      in hepatocytes through upregulation of Mn-SOD.
AB  - BACKGROUND/AIMS: Hypoxia/reoxygenation (H/R) causes oxidative stress to the cell
      and induces apoptotic cell death. Signal transducer and activator of
      transcription-3 (Stat3) is one of the most important molecules involved in the
      initiation of liver development and regeneration, and has recently been shown to
      protect cells against various pathogens. In order to investigate the
      hepatoprotective effects of Stat3, we examined whether it protects against H/R
      induced injury in primary hepatocytes. METHODS: Primary cultured hepatocytes were
      prepared from SD rats. Adenoviruses and cytokines were added 2 days and 1h prior
      to the H/R insult, respectively. Hepatocytes and culture media were harvested for
      the assays before and after H/R insult. RESULTS: Interleukin-6 and cardiotropin
      1, which may function mainly through Stat3 activation, protected cells from H/R
      induced apoptosis. Adenoviral overexpression of the constitutively activated form
      of Stat3 (Stat3-C) reduced H/R-induced apoptosis as well as generation of
      reactive oxygen species (ROS) in hepatocytes. Interestingly, Stat3-C induced Mn
      SOD, but not Cu/Zn-SOD, both at the protein and mRNA levels. Overexpression of Mn
      SOD significantly reduced H/R-induced ROS and apoptosis by inhibiting redox
      sensitive activation of caspase-3 activity. CONCLUSIONS: Stat3 protects
      hepatocytes from H/R-induced cell injury at least partly by upregulating Mn-SOD
      and inactivating caspase-3.

PMID- 15582130
TI  - Involvement of natural killer cells in PolyI:C-induced liver injury.
AB  - BACKGROUND/AIMS: The roles of T cells, natural killer T cells (NKT) and
      macrophages in autoimmune hepatitis have been well documented. However, the roles
      of natural killer (NK) cells in liver injury remain obscure. Here we examined the
      effect of Polyinosinic: polycytidylic acid (PolyI:C)-activated NK cells on liver
      injury. METHODS: Mice were intraperitoneally injected with PolyI:C at a dose of
      20mug/g body wt. The percentage and absolute number of NK cells in the liver were
      analyzed with flow cytometry. Serum alanine transaminase (ALT) and aspartate
      aminotransferase (AST) assay and H-E staining were used to evaluate the liver
      injury. RESULTS: Following PolyI:C injection, NK cells accumulation and
      activation occurred in the liver. Meanwhile, slight elevation of ALT/AST in the
      serum, mild inflammation and focal necrosis in the liver were also observed.
      Depletion of NK cells markedly attenuated PolyI:C-induced liver injury.
      Neutralization of endogenous Interleukin-12 produced by Kupffer cells abrogated
      the accumulation of NK cells in the liver and subsequent liver injury. The liver
      injury was also alleviated by neutralization of vascular cell adhesive molecule
      1. CONCLUSIONS: These findings suggest that PolyI:C preferentially recruits and
      activates hepatic NK cells, which may be responsible for the mild hepatitis.

PMID- 15582131
TI  - Suppression of transforming growth factor-beta results in upregulation of
      transcription of regeneration factors after chronic liver injury.
AB  - BACKGROUND/AIMS: To determine the effects of dominant-negative TGF-beta receptor
      expression during liver regeneration in rats with dimethylnitrosamine (DMN)
      induced liver injury. METHODS: Rats were first treated with DMN for 3 weeks, and
      then intravenously injected once with AdTbeta-TR, AdLacZ, or saline. Serial
      changes in hepatocyte proliferation and apoptosis were evaluated by
      immunohistochemistry using anti-Ki67 antibody, and TUNEL staining, respectively.
      The mRNA expression of regeneration factors (HGF, TGF-alpha, EGF, and IGF-I) and
      IL-6 were evaluated by real-time PCR and northern blotting. RESULTS: Anti-TGF
      beta molecular intervention up-regulated hepatocyte proliferation and inhibited
      apoptosis. In the AdTbeta-TR-treated rats, EGF and IGF-I mRNA expression levels
      were significantly increased at day 1 and remained high for 3 days after gene
      transfer; TGF-alpha mRNA expression levels were significantly increased at 2 to 5
      days after gene transfer; HGF mRNA expression levels were significantly up
      regulated at day 2 only after gene transfer; while IL-6 mRNA expression level
      tended to increase at day 1, but decreased thereafter. CONCLUSIONS: In rats with
      DMN-induced liver injury, anti-TGF-beta molecular intervention therapy stimulates
      proliferation and reduces apoptosis of hepatocytes, and also up-regulates the
      transcription of various growth factors.

PMID- 15582132
TI  - Progenitor cell expansion: an important source of hepatocyte regeneration in
      chronic hepatitis.
AB  - BACKGROUND/AIMS: Progenitor cell activation with subsequent maturation to
      hepatocytes and cells of the biliary lineage has been demonstrated in a variety
      of chronic liver diseases but the kinetics and magnitude of the progenitor cell
      response has not been adequately studied in detail in chronic hepatitis. We
      undertook this study to evaluate factors responsible for the progenitor
      cell/ductular response and further dissect the role of disease grade and stage as
      determinants of hepatocellular differentiation of bipotential progenitor cells in
      chronic hepatitis. METHODS: Cytokeratin 7 (and 19) stained biopsies from patients
      with chronic hepatitis C (n = 47), hepatitis B (n = 20), and autoimmune hepatitis
      (n = 20) were studied. Ploidy analysis and proliferation indices were evaluated
      in a subset of cases. RESULTS: Ductular reactions were present in the majority of
      cases (97%), appeared early in disease, and correlated with disease activity,
      while progenitor cell derived hepatocyes appeared later in disease and their
      extent correlated with disease stage. Proliferation indices of all cell types
      correlated with disease activity. CONCLUSIONS: Progenitor cell derived
      hepatocytes accrue in chronic hepatitis, possibly related to native
      hepatocellular dysfunction. However, the fate of these hepatocytes is unclear.

PMID- 15582133
TI  - Unique hypervascular nodules in alcoholic liver cirrhosis: identical to focal
      nodular hyperplasia-like nodules?
AB  - BACKGROUND/AIMS: Currently, focal nodular hyperplasia (FNH)-like nodules in
      cirrhotic liver is spotlighted. Unique hypervascular nodules mimicking FNH-like
      nodule in alcoholic liver cirrhosis were clinicopathologically clarified.
      METHODS: Six resected and six biopsy cases of small hypervascular nodules found
      in alcoholic cirrhosis were studied clinicopathologically. RESULTS: All cases
      were male and consumed 90-150 g/day of ethanol for longer than 20 years, and
      hepatitis virus markers were negative. The nodules, 9-21 mm in diameter, were
      detected by ultrasonography during follow-up of alcoholic cirrhosis, and showed
      hypervascularity on angiography. Six patients were diagnosed as hepatocellular
      carcinoma and six were as hyperplastic nodule by biopsy, and the former six cases
      received partial hepatectomy. All of the resected nodules were completely or
      incompletely encapsulated. Histologically, all resected and biopsy nodules showed
      moderate increase of cell-density with an irregular trabecular pattern, and scar
      like fibrosis with anomalous blood vessels, and unpaired arteries. All nodules
      showed marked or mild iron deposits in hepatocytes and/or kupffer cells, and a
      diffuse capillarization of the sinusoids. CONCLUSIONS: The nodules in the present
      series seem to fall in the same category as FNH-like nodules in cirrhotic liver,
      and should be taken account in screening programs including patients with
      alcoholic cirrhosis.

PMID- 15582134
TI  - Immunoregulation of dendritic and T cells by alpha-fetoprotein in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Novel immunotherapeutic and other strategies are being explored
      for the treatment of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) may
      be a target antigen for immunotherapy. Little is known, however, about the
      immunobiology of AFP. Therefore, the impact of AFP on dendritic cells (DC), CD4+
      and CD8+ T cells was studied in detail. METHODS: Immune cells from peripheral
      blood of 27 HCC patients were studied using FACS, ELISPOT, and proliferation
      assays. RESULTS: The in vitro generation, maturation, and T cell stimulatory
      capacity of DCs were not altered by AFP up to concentrations of 20 microg/ml.
      Higher AFP concentrations (> 20 microg/ml) resulted in phenotypic changes on DCs
      without impairing their capacity to stimulate CD4+ T cells. Frequencies and
      function of DCs and AFP specific T cells were not reduced in HCC patients
      independent on serum AFP levels. Finally, T lymphocytic infiltrations in the
      liver were not dependent on AFP serum levels. CONCLUSIONS: These studies clearly
      demonstrate that (i) DC-based immunotherapeutic approaches are a promising
      approach for HCC treatment and (ii) AFP-reactive T cell clones have not been
      deleted from the human T cell repertoire establishing AFP as a potential target
      for T cell based immunotherapy of HCC.

PMID- 15582135
TI  - Targeting the epidermal growth factor receptor by gefitinib for treatment of
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancer
      related causes of death worldwide. Due to very poor 5-year-survival new
      therapeutic approaches are mandatory. Gefitinib, an inhibitor of epidermal growth
      factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of
      various tumors, but its effect on HCC remains unexplored. We therefore studied
      the antineoplastic potency of gefitinib in human HCC cells. RESULTS: Gefitinib
      induced a time- and dose-dependent growth inhibition of the human HCC cell lines
      Huh-7 and HepG2. Gefitinib-treatment induced both mitochondria-dependent and 
      independent apoptosis. Changes in mitochondrial membrane potential and caspase-8
      activation, followed by caspase-3 activation and nuclear degradation, were
      detected. Moreover, gefitinib induced cell cycle arrest at the G1/S checkpoint
      and decreased the phosphorylation of mitogen-activated protein kinase ERK1/2.
      Finally, gefitinib suppressed the expression of antiapoptotic Bcl-2 and Bcl-X(L),
      further rendering HCC cells prone to apoptosis. CONCLUSIONS: Our data demonstrate
      that the inhibition of EGFR-TK by gefitinib induced growth inhibition, apoptosis
      and cell cycle arrest in human HCC cells. Thus, EGFR-TK inhibition appears to be
      a promising novel approach for future treatment strategies of HCC.

PMID- 15582137
TI  - Referral of chronic hepatitis B patients from primary to specialist care: making
      a simple guideline work.
AB  - BACKGROUND/AIMS: To evaluate a guideline selecting patients at the primary care
      level for referral to a specialist, to identify bottlenecks and subsequently
      implement and evaluate improvements. METHODS: Retrospective patient files
      analysis and a prospective cohort study. The study was conducted in Municipal
      Public Health Service (PHS), University Medical Center. Patients diagnosed with
      chronic hepatitis B virus (HBV) infection were referred to the PHS. Improvement
      of bottlenecks were identified in the referral chain, based on the guideline.
      Number of patients receiving correct advice, number of patients reaching the
      hospital for specialist care, time between notification of the PHS and final
      arrival in the hospital. RESULTS: The guideline for the referral of chronic HBV
      patients appeared to be appropriate, although one-third of the selected patients
      was not seen by the specialist. After the intervention more HBV patients (76
      versus 61%) received correct advice from the PHS, and the number of HBV patients
      seen by the specialist increased by 18%. CONCLUSIONS: The referral guideline
      works, yet we could improve the efficiency of the guideline increasing the
      proportion of eligible patients reaching specialist care. In countries where
      mandatory reporting of HBV infections exists this guideline can be adapted to
      local health systems.

PMID- 15582136
TI  - Rapid increase of bile salt secretion is associated with bile duct injury after
      human liver transplantation.
AB  - BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver
      transplantation. We have studied the role of altered bile composition as a
      mechanism of bile duct injury after human liver transplantation. METHODS: In 28
      liver transplant recipients, bile samples were collected daily
      posttransplantation for determination of bile composition. Hepatic expression of
      bile transporters was studied before and after transplantation. Histopathological
      criteria as well as biliary concentrations of alkaline phosphatase (ALP) and
      gamma-glutamyltransferase (gamma-GT) were used to quantify bile duct injury.
      RESULTS: Early after transplantation, bile salt secretion increased more rapidly
      than phospholipid secretion, resulting in high biliary bile salt/phospholipid
      ratio (BA/PL). In parallel with this, mRNA levels of the bile salt transporters
      NTCP and BSEP increased significantly after transplantation, whereas phospholipid
      translocator MDR3 mRNA levels remained unchanged. Bile duct injury correlated
      significantly with bile salt secretion and was associated with a high biliary
      BA/PL ratio. CONCLUSIONS: Bile salt secretion after human liver transplantation
      recovers more rapidly than phospholipid secretion. This results in cytotoxic bile
      formation and correlates with bile duct injury. These findings suggest that
      endogenous bile salts have a role in the pathogenesis of bile duct injury after
      liver transplantation.

PMID- 15582138
TI  - Predominance of type 1 (Th1) cytokine production in the liver of patients with
      HCV-associated mixed cryoglobulinemia vasculitis.
AB  - BACKGROUND/AIMS: Patients with hepatitis C virus (HCV) mixed cryoglobulinemia
      (MC) vasculitis have a higher mortality rate and more frequent incidence of
      cirrhosis than their cryoglobulin-negative counterparts. To compare the cytokine
      profile of liver-infiltrating T cells in HCV-infected patients with or without MC
      vasculitis. METHODS: Hepatic biopsy specimens were obtained from HCV infected
      patients with and without MC vasculitis. Using intracellular staining and flow
      cytometry, we assessed the ability of freshly isolated liver T cells from these
      biopsies to produce IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 in response to
      stimulation with PMA and ionomycin. RESULTS: HCV-MC vasculitis patients compared
      to HCV-MC negative controls have an enhanced hepatic T cells production of Th1
      type cytokines [i.e. TNF-alpha(30.3 +/- 13% vs. 15.5 +/- 5%, P = 0.01), IL-2
      (20.2 +/- 9% vs. 10 +/- 4%, P = 0.01) and IFN-gamma (22.2 +/- 11% vs. 9.4 +/- 4%,
      P = 0.008)], whereas IL-10, a representative Th2-type cytokine, was significantly
      lower (7.2 +/- 4% vs. 17 +/- 7%, P = 0.01). CONCLUSIONS: T cell from the liver of
      HCV-MC vasculitis patients display a significantly augmented liver Th1 profile
      compared to MC-negative controls. This enhanced production of type-1 cytokines
      may account for a more severe course of liver disease.

PMID- 15582139
TI  - Hepatic clearance of advanced glycation end products (AGEs)--myth or truth?

PMID- 15582140
TI  - Liver involvement in cystic fibrosis: primary organ damage or innocent bystander?

PMID- 15582141
TI  - Enhanced TH1 cytokine production in hepatitis C virus-infected patients with
      mixed cryoglobulinemia: understanding the pathological issues.

PMID- 15582142
TI  - Strategies for liver support: from stem cells to xenotransplantation.

PMID- 15582143
TI  - An intraluminal lesion in the mid-common bile duct and right hepatic duct causing
      right portal vein obstruction.

PMID- 15582144
TI  - Acute hepatitis of cholestatic type possibly associated with the use of
      glucomannan (amorphophalus konjac).

PMID- 15582145
TI  - Severe hepatotoxicity associated with the use of weight loss diet supplements
      containing ma huang or usnic acid.

PMID- 15582146
TI  - Combined interferon plus lamivudine treatment in young patients with dual HBV
      (HBeAg positive) and HCV chronic infection.

PMID- 15582147
TI  - Bronchobiliary fistula secondary to ruptured hepatocellular carcinoma into the
      bile duct.

PMID- 15582148
TI  - Unedited inhibition of HBV replication by APOBEC3G.

PMID- 15582150
TI  - The molecular genetics of the 22q11-associated schizophrenia.
AB  - Schizophrenia has a strong genetic component but the mode of inheritance of the
      disease is complex and in all likelihood involves interaction among multiple
      genes and also possibly environmental or stochastic factors. A number of studies
      have shown that the 22q11 deletion syndrome (22q11DS) is a true genetic subtype
      of schizophrenia and as such may play an extremely important role in deciphering
      the genetic basis of schizophrenia. Microdeletions of the 22q11 locus are
      associated with a staggering increased risk to develop schizophrenia. The same
      locus has also been implicated by some linkage studies. Systematic examination of
      individual genes from the 1.5 Mb critical region has identified so far the PRODH
      and ZDHHC8 as strong candidate schizophrenia susceptibility genes from this
      locus. Discovery of these genes implicates neuromodulatory aminoacids and protein
      palmitoylation as important for disease development. Other genes, including the
      gene encoding for COMT, have been implicated by candidate gene approaches. It
      therefore appears that the 22q11-associated schizophrenia may have the
      characteristics of a contiguous gene syndrome, where deficiency in more than one
      gene contributes to the strikingly increased disease risk. Mouse models for
      individual candidate genes will provide the investigators with the opportunity to
      start understanding the function of these genes and how they may impact on
      schizophrenia. Mouse models that carry long-range deletions will likely capture
      the interactions among the culprit genes and help explain the genetic
      contribution of this locus to the high risk for schizophrenia. In-depth human and
      animal model studies of 22q11DS promise to answer critical questions relating to
      the devastating illness of schizophrenia, whose causes remain largely unknown.

PMID- 15582151
TI  - Large-scale mutagenesis of the mouse to understand the genetic bases of nervous
      system structure and function.
AB  - N-ethyl-N-nitrosourea (ENU) mutagenesis is presented as a powerful approach to
      developing models for human disease. The efforts of three NIH Mutagenesis Centers
      established for the detection of neuroscience-related phenotypes are described.
      Each center has developed an extensive panel of phenotype screens that assess
      nervous system structure and function. In particular, these screens focus on
      complex behavioral traits from drug and alcohol responses to circadian rhythms to
      epilepsy. Each of these centers has developed a bioinformatics infrastructure to
      track the extensive number of transactions that are inherent in these large-scale
      projects. Over 100 new mouse mutant lines have been defined through the efforts
      of these three mutagenesis centers and are presented to the research community
      via the centralized Web presence of the Neuromice.org consortium
      (http://www.neuromice.org). This community resource provides visitors with the
      ability to search for specific mutant phenotypes, to view the genetic and
      phenotypic details of mutant mouse lines, and to order these mice for use in
      their own research program.

PMID- 15582152
TI  - A neurogenomics approach to gene expression analysis in the developing brain.
AB  - Secreted and transmembrane proteins provide critical functions in the signaling
      networks essential for neurogenesis. We used a genetic signal sequence gene trap
      approach to isolate 189 genes expressed during development in e16.5 whole head,
      e16.5 hippocampus and e14.5 cerebellum. Gene ontology programs were used to
      classify the genes into respective biological processes. Four major classes of
      biological processes known to be important during development were identified:
      cell communication, cell physiology processes, metabolism and morphogenesis. We
      used in situ hybridization to determine the temporal and spatial patterns of gene
      expression in the developing brain using this set of probes. The results
      demonstrate that gene expression patterns can highlight potential gene functions
      in specific brain regions. We propose that combining bioinformatics with the gene
      expression pattern is an effective strategy to identify genes that may play
      critical roles during brain development.

PMID- 15582153
TI  - Identification of candidate Purkinje cell-specific markers by gene expression
      profiling in wild-type and pcd(3J) mice.
AB  - The identification of mRNAs that have restricted expression patterns in the brain
      represents powerful tools with which to characterize and manipulate the nervous
      system. Here, we describe a strategy using microarray technology (Affymetrix
      Mouse Genome 430 2.0 Arrays) to identify mRNA transcripts that are candidate
      markers of cerebellar Purkinje neurons. Initially, gene expression profiles were
      compared between cerebella of 4-month-old Purkinje cell degeneration (pcd(3J))
      mice, in which most Purkinje cells had already degenerated and wild-type
      littermates with a normal complement of Purkinje neurons. Of 14,563 probe sets
      expressed in wild-type cerebellum, 797 showed a significant (p<0.0001) reduction
      in pcd(3J) mice. These probes could represent transcripts with varying levels of
      specificity for Purkinje cells as well as transcripts in other cell types that
      decline as a secondary consequence of Purkinje cell loss. Ranking of the probe
      signals revealed that well-known Purkinje cell-specific transcripts such as
      calbindin and L7/pcp2 clustered in a group that was <33% of wild-type levels.
      Therefore, to identify potentially new Purkinje cell-specific transcripts that
      cluster with the known markers, more stringent selection criteria were applied
      (<33% of wild-type signal and p<0.0001). With these criteria, 55 independent
      transcripts were identified of which 33 were annotated genes and 22 were ESTs and
      RIKEN cDNAs. A literature search revealed that 25 of the 33 annotated genes were
      expressed in Purkinje cells, with no data being available on the other 8. Thus,
      the additional 8 annotated and 22 un-annotated genes are clustered with many
      genes expressed in Purkinje cells making them candidate markers. To confirm the
      microarray data, eight representative annotated genes were selected including
      five reported to be in Purkinje neurons and three for which no data was
      available. Semi-quantitative RT-PCR demonstrated reduced expression of all eight
      transcripts in cerebella from pcd(3J) mice. The promoters of genes expressed
      selectively in subsets of neurons can be used to direct heterologous gene
      expression in transgenic mice and the more restricted the expression pattern the
      greater their utility. Therefore, microarray analysis was used to assess
      expression levels of all 55 transcripts in cerebral cortex, striatum, substantia
      nigra and ventral tegmental area. This permitted the identification of a set of
      genes whose promoters might have utility for selectively targeting gene
      expression to cerebellar Purkinje cells.

PMID- 15582154
TI  - DeltaFosB: a molecular switch for long-term adaptation in the brain.
AB  - DeltaFosB is a unique transcription factor that plays an essential role in long
      term adaptive changes in the brain associated with diverse conditions, such as
      drug addiction, Parkinson's disease, depression, and antidepressant treatment. It
      is induced in brain, in a region- and cell-type-specific manner by many types of
      chronic perturbations. Once induced, it persists for long periods of time due to
      its unusual stability. The transcriptional effects of DeltaFosB are complex,
      because the protein can function as both a transcriptional activator and
      repressor. Progress has been made in identifying specific target genes for
      DeltaFosB and in relating some of these genes to DeltaFosB's cellular and
      behavioral actions. Future studies will help us to better understand the
      biochemical basis of DeltaFosB's unique stability, as well as the precise
      molecular pathways through which this transcription factor produces its complex
      effects on neuronal plasticity and complex behavior.

PMID- 15582155
TI  - Human blood genomics: distinct profiles for gender, age and neurofibromatosis
      type 1.
AB  - Application of gene expression profiling to human diseases will be limited by
      availability of tissue samples. It was postulated that germline genetic defects
      affect blood cells to produce unique expression patterns. This hypothesis was
      addressed by using a test neurological disease-neurofibromatosis type 1 (NF1), an
      autosomal dominant genetic disease caused by mutations of the NF1 gene at
      chromosome 17q11.2. Oligonucleotide arrays were used to survey the blood gene
      expression pattern of 12 NF1 patients compared to 96 controls. A group of genes
      related to tissue remodeling, bone development and tumor suppression were down
      regulated in NF1 blood samples. In addition, there were blood genomic patterns
      for gender and age: Y chromosome genes showing higher expression in males,
      indicating a gene-dosage effect; and genes related to lymphocyte functions
      showing higher expression in children. The results suggest that genetic mutations
      can be manifested at the transcriptional level in peripheral blood cells and
      blood gene expression profiling may be useful for studying phenotypic differences
      of human genetic diseases and possibly providing diagnostic and prognostic
      markers.

PMID- 15582156
TI  - Time-dependent changes in transcriptional profiles within five rat brain regions
      in response to nicotine treatment.
AB  - Many years of behavioral and neurobiology studies have demonstrated broad
      physiological and pharmacological effects of nicotine on the central nervous
      system (CNS). However, the gene expression profiles associated with these effects
      are largely unknown. In this study, we characterized gene expression profiles in
      the prefrontal cortex, striatum, hypothalamus, amygdala and ventral tegmental
      area of the rat brain in response to subacute and chronic systemic nicotine
      administration using a pathway-focused microarray developed in this laboratory
      that contains 638 sequence-verified genes representing broad, yet targeted,
      biological functions. By comparing the regional effects of nicotine treatment on
      gene expression levels, we derived the expression profiles of targeted genes and
      gene families responding to the new environment created by nicotine throughout
      the complex connections of the CNS. While the expression of many genes was
      modulated by nicotine in several regions, only a few were co-modulated in
      multiple brain regions, suggesting region-specific transcriptional responses.
      Cluster analysis of significantly altered genes within each brain region over the
      course of nicotine treatment indicated the genes could be grouped into clusters.
      Subsequent ANOVA analysis demonstrated these clusters within each brain region to
      be significantly different at most time points. The clusters were comprised of
      broad functional groups, such as signaling, neurotransmission and protein
      modifications, demonstrating unique expression patterns within each region. Using
      a systematic approach to compare the different regional responses to nicotine
      administration will eventually provide a better understanding of how the
      different brain regions responding to this drug.

PMID- 15582157
TI  - Nicotine coregulates multiple pathways involved in protein
      modification/degradation in rat brain.
AB  - Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol
      and MAP kinase signaling pathways are regulated by nicotine in different rat
      brain regions. In the present report, we show that, after exposure to nicotine
      for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal
      subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are
      upregulated in rat prefrontal cortex (PFC) while being downregulated in the
      medial basal hypothalamus (MBH). In particular, relative to saline controls,
      ubiquitins B and C were upregulated by 33% and 47% (P<0.01), respectively, in the
      PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were
      upregulated in the PFC by 95% and 119% (P<0.001), respectively. In addition to
      the protein degradation pathway of the ubiquitin-proteasome complexes, we
      observed in the PFC an increase in the expression of small, ubiquitin-related
      modifiers (SUMO) 1 and 2 by 80% and 33%, respectively (P<0.001), and in 3 of 6
      CCT subunits by up to 150% (P<0.0001). To a lesser extent, a change in the
      opposite direction was obtained in the expression of the same gene families in
      the MBH. Quantitative real-time RT-PCR was used to validate the microarray
      results obtained with some representative genes involved in these pathways. Taken
      together, our results suggest that, in response to systemic nicotine
      administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide
      an intricate control mechanism to maintain cellular homeostasis, possibly by
      regulating the composition and signaling of target neurons in a region-specific
      manner.

PMID- 15582158
TI  - Targeting hearing genes in mice.
AB  - The rate of identification of genes for hearing has clearly outpaced the rate of
      determination of the functions of these genes' products. The use of transgenic
      and knock-out mouse models is a powerful approach to the elucidation of gene
      function in the ear. A large number of gene-targeted mice with auditory defects
      have recently been created and characterized, and nine independent mouse lines in
      which Cre recombinase activity begins to be expressed during early embryonic
      development of the ear or is specifically expressed in hair cells during
      postnatal development will be useful for ear-specific gene manipulation when
      combined with mouse lines that have loxP sites flanking the genes of interest.
      Existing gene-trapped embryonic stem (ES) cells and existing targeting constructs
      are readily available; new targeting constructs can easily be created by
      modifying bacterial artificial chromosomes and using them to directly transfect
      and screen ES cells; and N-ethyl-N-nitrosourea mutagenesis of ES cells can create
      point mutations in specific genes. To minimize variation in hearing phenotypes
      and avoid undesired hearing defects, mutant mice in the common gene-targeting
      background strains (129 and C57BL/6) should be transferred into congenic CBA/CaJ,
      a strain with "gold standard" normal hearing. Valuable mutant strains can be
      maintained, distributed, and cryopreserved in one of four NIH-sponsored Mutant
      Mouse Regional Resource Centers. Targeting hearing genes in mice will provide
      unprecedented opportunities for collaboration and new directions in the hearing
      research community.

PMID- 15582159
TI  - Retinal degeneration in Aipl1-deficient mice: a new genetic model of Leber
      congenital amaurosis.
AB  - Leber congenital amaurosis (LCA) is the most severe inherited retinopathy, with
      the earliest age of onset. Because this currently incurable disease is present
      from birth and is a relatively rare disorder, the development of animal models
      that closely resemble the phenotype in patients is especially important. Our
      previous genetic analyses of LCA patients identified mutations in the aryl
      hydrocarbon interacting protein-like 1 (AIPL1) gene. Here we present development
      of an animal model of AIPL1-associated LCA, the Aipl1-deficient mouse. Aipl1 is
      expressed at low levels throughout human and mouse retinal development and is
      rapidly upregulated as photoreceptors differentiate. The mouse displays rapid
      retinal degeneration and massive Muler cell gliosis, resembling the phenotype of
      the rd mouse, which is caused by a mutation in the gene for the beta-subunit of
      the rod-specific phosphodiesterase. We confirm that this phenotype is consistent
      with the human disease using electroretinograms, and document the disease
      pathogenesis by analyzing the development of all retinal cell types and
      synaptogenesis during retinal histogenesis. Ectopic expression of AIPL1 led to
      deregulated retinal progenitor cell proliferation and alterations in cell fate
      specification; however, no gross abnormalities of proliferation during retinal
      development were detected. Data from analysis of proliferation and cell fate
      specification during retinal development of Aipl1-deficient mice suggests that
      there may be redundancy or compensation for Aipl1 loss by other related proteins.
      Because this mouse model closely mimics the human retinopathy caused by
      homozygous mutations in this gene, it provides a preclinical model for testing
      therapies to rescue the vision of children whose blindness is caused by AIPL1
      mutations.

PMID- 15582160
TI  - Expression of Bcl-2 extends the survival of olfactory receptor neurons in the
      absence of an olfactory bulb.
AB  - In the olfactory neuroepithelium, the number of olfactory receptor neurons (ORNs)
      is maintained at a relatively constant level by a precise balance between the
      elimination of mature receptors and proliferation of their precursors. However,
      little is known of the mechanisms that couple alterations in receptor death rates
      to changes in precursor proliferation. To investigate this relationship, we
      generated a line of mice expressing Bcl-2, a protein with anti-apoptotic
      properties, in mature olfactory receptor neurons using the Olfactory Marker
      Protein (OMP) promoter. OMP-bcl-2 transgenic mice showed selective expression of
      Bcl-2 in mature sensory neurons of the olfactory neuroepithelium (ONE) and
      vomeronasal organ. Olfactory bulbectomy (OBX) resulted in the death of mature
      receptor neurons followed by the sustained proliferation of their precursors in
      wild-type and OMP-bcl-2 transgenic mice. The persistently enhanced proliferation
      of olfactory neuroblasts that followed bulbectomy was indistinguishable between
      transgenic and non-transgenic mice. However, receptor neurons that were
      subsequently born in the absence of the bulb had longer life spans in OMP-bcl-2
      mice. The increased proliferation of neuroblasts and extended life spans combined
      to restore near normal numbers of olfactory receptors in bulbectomized OMP-bcl-2
      mice. A model is proposed to explain the dissociation of death and proliferation
      in OMP-bcl-2 transgenic mice.

PMID- 15582161
TI  - Expression of axotomy-inducible and apoptosis-related genes in sensory nerves of
      rats with experimental diabetes.
AB  - In diabetes, peripheral nerves suffer deficient neurotrophic support-a situation
      which resembles axotomy. This raises the question: does inappropriate
      establishment of an axotomised neuronal phenotype contribute to diabetic
      neuropathy, and in extremis, does this provoke apoptosis? We hybridized reverse
      transcribed RNA, from the dorsal root ganglia (DRG) of 8-week streptozotocin
      (STZ)-induced diabetic rats, to Affymetrix Rat Genome U34A chips and scanned the
      array for expression of (a) genes that are upregulated by axotomy, (b)
      proapoptotic and (c) anti-apoptotic genes. Expression of the axotomy-responsive
      genes coding for growth-associated protein 43 (GAP-43), galanin, neuropeptide Y
      (NPY), pre-pro-vasoactive intestinal polypeptide (pre-pro-VIP), neuronal nitric
      oxide synthase (nNOS), protease nexin 1, heat-shock protein 27 (HSP 27) and
      myosin light chain kinase II (MLCK II) was unaffected in ganglia from diabetic
      rats compared to controls; thus, no axotomised phenotype was established. The
      expression of the majority of proapoptotic genes in the DRG was also unaltered
      (bax, bad, bid, bok, c-Jun, p38, TNFR1, caspase 3 and NOS2). Similarly there was
      no change in expression of the majority of antiapoptotic genes (bcl2, bcl-xL, bcl
      w, NfkappaB). These alterations in gene expression make it clear that neither
      axotomy nor apoptotic phenotypes are established in neurones in this model of
      diabetes.

PMID- 15582162
TI  - Early dysregulation of hippocampal proteins in transgenic rats with Alzheimer's
      disease-linked mutations in amyloid precursor protein and presenilin 1.
AB  - The response of the hippocampal proteome to expression of mutant proteins present
      in familial forms of Alzheimer's disease (AD) was studied using transgenic rats.
      These animals carry both the amyloid precursor protein Swedish and 717 mutation
      (APP(SW+717)) as well as the presenilin 1 Finnish mutation (PS1(FINN)). This
      transgenic rat model displays intracellular amyloid beta (Abeta) in neurons of
      the neocortex and the hippocampus (CA2 and CA3). The hippocampus was selected as
      it is one of the first brain regions affected in AD and is involved in the
      processing of short-term memory and spatial memory. Applying a proteomic
      approach, we demonstrate that the expression of APP(SW+717) and PS1(FINN)
      transgenes causes changes in expression of hippocampal proteins, some of which
      have been previously linked to learning and memory formation. The protein
      alterations documented here occur in the absence of plaque formation and prior to
      the onset of cognitive deficits later observed in these transgenic rats. This
      indicates that molecular changes take place in the hippocampal neurons in
      response to expression of mutant proteins APP(SW+717) and PS1(FINN), which
      precede the occurrence of overt extracellular accumulation of extracellular
      amyloid. The implications of these findings on our understanding of the early
      stages of AD are discussed.

PMID- 15582163
TI  - RNA interference in neuroscience.
AB  - One of the most exciting findings in recent years has been the discovery of RNA
      interference (RNAi). RNAi is an important system that allows sequence-specific
      gene silencing through targeted degradation of mRNA by cognate double-stranded
      RNA (dsRNA). RNAi plays a role in endogenous cellular processes, such as
      developmental control and heterochromatin formation, and serves as an antiviral
      defense mechanism. Recent findings suggest that RNAi and related pathways are
      involved in protecting the genome against instabilities caused by transposons and
      repetitive sequences. Several rapidly developing RNAi methodologies provide a new
      approach for elucidation of gene functions. RNAi technology is also currently
      being evaluated as a potentially useful method to develop highly specific dsRNA
      based gene-silencing therapeutics. In this paper, we review the use of RNAi in
      neuroscience research and as a possible therapeutic tool for treatment of
      neurological diseases.

PMID- 15582164
TI  - [What goals for plasma glucose level in elderly diabetic patients? Is there any
      consensus?].

PMID- 15582165
TI  - [Cold agglutinins, clinical presentation and significance; retrospective analysis
      of 58 patients].
AB  - PURPOSE: To describe clinical, biological characteristics and associated diseases
      of cold agglutinins in adults. METHODS: Retrospective study in a single
      department of internal medicine from 1997 to 2002. The inclusion criteria were a
      positive direct Coombs test and a positive research for cold-reactive
      autoantibodies. We recorded for each patient: clinical presentation at onset and
      during follow-up, biological parameters of haemolysis, biological characteristics
      of the cold agglutinin and associated diseases. RESULTS: Fifty-eight patients (34
      females, 24 males), with medium age of 58.8 were included in the study. Clinical
      presentation was highly variable between acute life-threatening haemolysis and
      absence of symptoms. Results of direct antiglobulin test were C3 (74%), IgG + C3
      (22.4%), IgG (3.4%). Titer, thermal amplitude, strength and specificity of Coombs
      test were correlated, in all cases except 6, with cold agglutinin haemolytic
      activity. In 77.6% of cases cold agglutinin was secondary; related to: autoimmune
      disorders (n = 19), lymphoproliferative disorders (n = 11) and infections (n =
      10). CONCLUSION: Clinical presentation of cold agglutinin is highly variable and
      not always related to the biological characteristics of the bound antibody
      (titer, thermal amplitude, specificity). In our single center study, diseases
      associated with cold agglutinin were various with the highest frequency of auto
      immune disorders. Our study underlined also the high frequency of
      lymphoproliferative disorders and justifies a close follow-up of these patients.
      Finally, we reported a high frequency of hepatitis C virus infection among the
      infectious aetiologies.

PMID- 15582166
TI  - [Prognosis of post-irradiation soft-tissue sarcoma: case-control study].
AB  - PURPOSE: We describe clinical and pathological aspects and survival of 12 recent
      of radio-induced soft tissue sarcoma. METHOD: We performed a single center case
      control study, with 23 control matched by grade (according to Federation
      nationale des centres de lutte contre le cancer Grading) and by location.
      Survival comparison used Log Rank test. RESULTS: The development of these 12
      cases was a result of 12 previous cancer treatment (including 4 breast cancers
      and 2 cervix cancers) with radiotherapy (median dose of 58 Grays). The median
      latency period was 10 years. There were nine women and three men. The median age
      was 68.5 years. The main location was chest wall (5 cases). The two main
      histologic subtypes were malignant histiocytofibromas (6 cases) and angiosarcomas
      (3 cases). Five cases were high grade. Treatments were performed with curative
      intent in 9 cases, including complete resection in six cases. Clinical and
      pathological aspects and treatments of controls were similar, but postoperative
      radiotherapy was most frequent and malignant histiocytofibroma was less common.
      Median overall survival (47 months vs. 30 months, P = 0.6), median metastatic
      disease-free survival (37 vs. 15 m., P = 0.6) and median locoregional disease
      free survival (14 vs. 24 m., P = 0.07) were similar for cases and control.
      CONCLUSION: This study suggests that prognosis of radio-induced soft-tissue
      sarcomas is similar as other soft tissue sarcoma of same grade and same location.

PMID- 15582167
TI  - [Vitamin C deficiency].
AB  - BACKGROUND: Hypovitaminosis C is frequent in populations at risk (men who live
      alone, old people, homelessness, patients with psychiatric diseases,
      foodfaddists,...) and is underestimated in the general population. STRONG POINTS:
      Scurvy occurs after 3 months without consumption of ascorbic acid, and is due to
      lack of consumption fresh fruits and vegetables. Clinical manifestations are
      weakness, myalgia and arthralgia, vascular purpura and hemorrhagic syndrome, and
      later the stomatologic manifestations: gingivorragia and loss of teeth.
      Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia.
      Clinical suspicion must be confirmed by a low level of ascorbic acid (<2.5 mg/l),
      but this value needs to be interpretated according to the presence of an acute
      phase response. Leucocyte ascorbic acid level reflects total body store and is
      more reliable, but not available in practice. Treatment consists in
      administration of 1 g vitamin C per day during 15 days. PERSPECTIVES: Vitamin C
      depletion (serum ascorbic acid level between 2 and 5 mg/l) may occur long-term
      complications such as increase cardiovascular and neoplasic risks or cataract.
      The new recommended dietary allowance of vitamin C (110 mg per day for an adult)
      takes into account of these risks.

PMID- 15582168
TI  - [Retinal vascular occlusions: diagnosis and management].
AB  - PURPOSE: The diagnosis of retinal venous and arterial occlusions is usually
      easily evoked on visual symptoms and ophthalmoscopic features. However, their
      management (etiologic explorations and treatment) has not been formally
      established and remains controversial. CURRENT KNOWLEDGE AND KEY POINTS: Some
      retinal vascular occlusions may result of loco-regional ocular causes. They more
      often occur in patients with cardiovascular pathologies or risk factors, or
      sometimes other systemic diseases that need to be recognized for a proper
      treatment. Therefore, a comprehensive management of patients with retinal
      vascular occlusions is necessary to correct associated diseases or predisposing
      abnormalities that could lead to local recurrences or systemic events.
      CONCLUSION: Along with a review of the literature, we suggest a practical
      approach for the management of retinal vascular occlusions, which requires a
      collaboration between the ophthalmologist and other physicians: general
      practitioner, cardiologist, internist... as appropriate according to each case.

PMID- 15582169
TI  - [2000 classification of idiopathic interstitial lung diseases].
AB  - OBJECTIVES: Diagnosis of interstitial lung diseases was recently improved by the
      use of diagnostic tools, such as high-resolution Computed Tomography, and by new
      insights in their pathogenesis and histology. This led the American Thoracic
      Society and the European Respiratory Society to propose a new classification of
      these diseases, in the aim to facilitate early diagnosis and specific care.
      CURRENT KNOWLEDGE AND KEY POINTS: Standard radiography gives the first suspicion
      of chronic diffuse infiltrative lung disease, and anamnesis and physical
      examination are essential steps of etiological diagnosis. High-Resolution
      computed tomography confirms the diagnosis of diffuse infiltrative lung disease.
      Longitudinal lung function tests are essential to assess the consequences of the
      lung disease. Lung biopsies are often, but not systematically, a useful tool. The
      2000 classification consists of seven entities of idiopathic interstitial
      diseases which are defined on clinical, radiological and pathological criteria:
      idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, cryptogenic
      organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis
      associated interstitial lung disease, desquamative interstitial pneumonia and
      lymphoid interstitial pneumonia. The most frequent is Idiopathic Pulmonary
      Fibrosis, which has a poor prognosis. FUTURE PROSPECT AND PROJECTS: This new
      classification results from a multidisciplinary confrontation with chest
      physicians, radiologists and pathologists. A better characterization of
      anatomoclinical entities should lead to a better pronostic evaluation, more
      informative comparisons of published studies, and therefore to rational
      therapeutic approach.

PMID- 15582170
TI  - [Venous tromboembolic treatment in patients with cancer].
AB  - PURPOSE: Venous tromboembolic treatment in patients with cancer can be a clinical
      dilemma. Comorbid conditions, significant risk of recurrence of bleeding
      associated with warfarin, difficult venous access, are some of the factors that
      often complicate anticoagulants therapy in patients with cancer. EXEGESIS: Low
      molecular weight heparin has replaced unfractionated heparin as the first line
      treatment in the majority of patients with venous thromboembolism and cancer, in
      hospital or safely at home. Recent trial demonstrated that long-term low
      molecular weight heparin administrated over a 6-month period reduced the rate of
      recurrence venous thromboembolism with non increase in bleeding compared with
      oral anticoagulant therapy. Placement of an inferior vena caval filter should be
      reserved for patients with active or very high risk of bleeding, but oncologist
      should consider these sobering results in such patients. Whether anticoagulants
      might also improve cancer survival rates independent of their effect on
      thromboembolism deserves further investigation. PERSPECTIVE: In future, new
      antithrombotic agents such as oral direct thrombin or long-acting synthetic
      factor Xa inhibitor may be useful in these patients.

PMID- 15582171
TI  - [Liver abscesses secondary to sigmoid diverticulitis: report of four cases].
AB  - INTRODUCTION: Pyogenic liver abscess often revealed by right sided abdominal pain
      and fever is a serious and life-threatening pathology. Biliary tract disease is
      the origin of the abscess in most cases but sometimes remains unidentified. A
      sigmoid septic source sometimes paucisymptomatic or hidden by an
      immunosuppressive treatment must be looked for. EXEGESIS: Here are four
      observations of liver abscesses, which are secondary to unknown sigmoiditis. The
      etiologic diagnosis was made either by abdomino-pelvic computed tomography or by
      enema with water-soluble products completed by a coloscopy. Each patient's liver
      abscesses were emptied by aspiration or catheter drainage in conjunction with
      antibiotics. Surgical treatment of sigmoiditis was performed either at the same
      time or later. CONCLUSION: Any liver abscess of unknown origin must lead to a
      search for unknown or disguised septic sigmoid pathology. Most of the time,
      injected abdomino-pelvic computed tomography makes the diagnosis possible, but
      enema associated with coloscopy is sometimes necessary.

PMID- 15582172
TI  - [Cerebral thrombophlebitis revealing hyperthyroidism: two cases report and
      literature review].
AB  - INTRODUCTION: Two cases of hyperthyroidism revealed by a cerebral venous
      thrombosis are reported. EXEGESIS: Clinical symptomatology consisted of intra
      cranial hypertension and convulsive crisis associated to thyrotoxicosis.
      Evolution was favorable with etiologic and symptomatic therapy. CONCLUSION: The
      cerebral venous thrombosis risk on hyperthyroidism is discussed.

PMID- 15582173
TI  - [Non-histaminic angiodema management: diagnostic and therapeutic interest of
      tranexamic acid].
AB  - INTRODUCTION: The diagnosis of chronic angioedema (localised and reversible
      oedema) is sometimes very difficult when there is no efficiency of anti
      histaminics and corticosteroids. In these cases, bradykinin angioedema must be
      mentioned. Tranexamic acid is efficient and must be proposed. STUDY: We reported
      seven patients who have a non-histaminergic angioedema since an average of 8
      years. Corticosteroids and histamine-1 blockers were not efficient. Daily
      tranexamic acid treatment (1 g x 3 per day) controlled the disease. Three
      patients had no more attack. The C1Inh antigen and function levels were normal.
      No secondary effect was described and all patients are still being treated
      (average of 20 months). CONCLUSION: When a non-histaminergic angioedema is
      suspected, tranexamic acid must be proposed as attack's treatment and as
      prophylactic treatment.

PMID- 15582174
TI  - [Muscular haematoma in Henoch-Schonlein purpura].
AB  - INTRODUCTION: Henoch-Schonlein purpura is one of the most frequent systemic
      vasculitis in children. In adults, muscle involvement is extremely rare and not
      very well characterized. We report a case of Henoch-Schonlein purpura with severe
      skin and renal involvement in witch multiple intramuscular haematoma leaded to
      severe anaemia. Histological examination confirms the muscle localization of the
      disease. EXEGESIS: A 68 years old man treated by oral anticoagulation for
      multiple venous thrombosis, was admitted with necrotic vasculitis of the skin,
      abdominal pain and segmental IgA glomerulopathy. The diagnosis of Henoch
      Schonlein purpura was rapidly made and intensive steroid therapy started. After
      rapid improvement, a haemorrhagic shock due to voluminous intramuscular haematoma
      was diagnosed by MRI. Histological examination of the muscle, confirms the
      localization of the disease. CONCLUSION: Intramuscular haematomas are very
      uncommon in Henoch-Schonlein purpura. There are usually a consequence of muscular
      immune complex vasculitis. In our patient, high dose corticosteroid was not
      unable to control the disease.

PMID- 15582175
TI  - [A group fever: safari's fever].
AB  - INTRODUCTION: Acute schistosomiasis, called safari's fever in Africa and Katayama
      fever in Japan, is an immunoallergic reaction due to transcutaneous penetration
      of infective cercaria. We report the collective case of seven young adults
      spending holidays in Mali. EXEGESIS: An eighteen years-old girl presents fever,
      headache, diarrhoea and abdominal pains at return from Dogon country (south of
      Mali). After turned down malaria and with the notion of bathing in fresh water
      followed by pruritus, we think to safari's fever. So we alarm all other members
      of the group. All can be treated to avoid chronic schistosomiasis. CONCLUSION:
      These observations recall that acute schistosomiasis is a real danger for
      tourists when bathing in fresh water in endemic areas of Africa. Education of
      travellers is necessary. Occurrence of safari's fever should alert physicians to
      prevent chronic schistosomiasis.

PMID- 15582177
TI  - [Porcelain gallbladder].

PMID- 15582176
TI  - [Scurvy].

PMID- 15582178
TI  - [Adult onset Still's disease associated with bronchiolitis obliterans organizing
      pneumonia].

PMID- 15582179
TI  - [Cellulitis due to penicillin-resistant Streptococcus pneumoniae].

PMID- 15582181
TI  - [Editorial].

PMID- 15582180
TI  - [Toxocariasis and cutaneous vasculitis].

PMID- 15582182
TI  - [The brain and diabetes].

PMID- 15582183
TI  - [The heart and diabetes].

PMID- 15582184
TI  - [Arteriopathies of the lower limbs in diabetes].

PMID- 15582185
TI  - [The kidney and diabetes].

PMID- 15582186
TI  - [Vaccination in geriatrics].

PMID- 15582187
TI  - [Nutritional strategies in geriatrics].

PMID- 15582188
TI  - [Hypertension in the aged].

PMID- 15582189
TI  - [Rights of the aged sick dependents].

PMID- 15582190
TI  - [Techniques of and indications for subcutaneous injections in geriatrics].

PMID- 15582191
TI  - Effect of ethanol on the tumorigenicity of urethane (ethyl carbamate) in B6C3F1
      mice.
AB  - Urethane is a carcinogen to which there is widespread exposure through the
      consumption of fermented foods and alcoholic beverages. In this study, we have
      assessed the carcinogenicity of urethane in combination with ethanol. Male and
      female B6C3F(1) mice (48 mice per sex per group) were exposed to 0, 10, 30, or 90
      ppm urethane in the presence of 0%, 2.5%, or 5% ethanol in drinking water ad
      libitum for two years, at which time the extent of tumorigenesis was assessed.
      Additional mice (four per sex per group) received the same doses for four weeks
      to assess serum levels of urethane and ethanol, DNA adduct formation, and the
      induction of microsomal cytochromes P450, cell proliferation, and apoptosis.
      Urethane decreased cell replication in the livers of female, but not male, mice,
      decreased cell replication in the lungs of both sexes, and induced cytochrome
      P450 2E1 in the livers of female mice. Hepatic levels of the DNA adduct 1,N(6)
      ethenodeoxyadenosine were increased by exposure to urethane and decreased by
      treatment with ethanol. Animal weights and survival were not affected by ethanol;
      in contrast, urethane administration decreased body weights and survival.
      Urethane caused dose-dependent increases in liver, lung, and harderian gland
      adenoma or carcinoma and hemangiosarcoma of the liver and heart in both sexes,
      mammary gland and ovarian tumors in females, and squamous cell papilloma or
      carcinoma of the skin and forestomach in males. The increase in hepatocellular
      tumors occurred in a relatively linear manner and was attributed to the formation
      of 1,N(6)-ethenodeoxyadenosine in hepatic DNA coupled with an increase in cell
      replication. Hemangiosarcomas were observed only at the 90 ppm urethane dose and
      were probably a result of high-dose urethane-induced toxicity. Lung
      alveolar/bronchiolar and harderian gland adenoma or carcinoma increased in a
      relatively linear manner, suggestive of a genotoxic mechanism for tumor
      induction. Ethanol induced a dose-dependent trend in hepatocellular adenoma or
      carcinoma in male mice, with the incidence being marginally increased at the
      highest dose. In female mice administered 10 ppm and 90 ppm urethane, ethanol
      caused dose-related increases in alveolar/bronchiolar adenoma or carcinoma and
      hemangiosarcoma of the heart, respectively. This may be due to ethanol decreasing
      the first-pass clearance of urethane, thus, increasing systemic distribution. In
      male mice a different relationship was observed: ethanol caused a dose-related
      decrease in alveolar/bronchiolar and harderian gland adenoma or carcinoma in mice
      administered 30 ppm urethane.

PMID- 15582192
TI  - Absence of toxic effects in F344/N rats and B6C3F1 mice following subchronic
      administration of chromium picolinate monohydrate.
AB  - Chromium picolinate monohydrate (CPM) is a synthetic compound heavily marketed to
      consumers in the United States for use as a dietary supplement for muscle
      building and weight loss. The National Toxicology Program (NTP) tested the
      toxicity of this compound based on the potential for widespread consumer exposure
      and lack of information about its toxicity. Groups of 10 male and 10 female
      F344/N rats and B6C3F(1) mice were exposed to 0, 80, 240, 2000, 10,000, or 50,000
      ppm CPM in feed for 13 weeks. CPM administration produced no effect on body
      weight gain or survival of rats or mice. Organ weights and organ/body weight
      ratios in exposed animals were generally unaffected by CPM. No compound-related
      changes in hematology and clinical chemistry parameters were observed. There were
      no histopathological lesions attributed to CPM in rats or mice.

PMID- 15582193
TI  - Applicability of an in vitro digestion model in assessing the bioaccessibility of
      mycotoxins from food.
AB  - Food is considered a major route of exposure to many contaminants. Only the
      fraction of the contaminant that is released from the food (bioaccessibility) and
      is bioavailable can exert toxic effects. Insufficient knowledge on the
      bioavailability may hamper an accurate risk assessment of ingested contaminants
      in humans. This paper describes the applicability of an in vitro digestion model
      allowing for measurement of the bioaccessibility of ingested mycotoxins from food
      as an indicator of oral bioavailability. Bioaccessibility of aflatoxin B(1) from
      peanut slurry and ochratoxin A from buckwheat was high, 94% and 100%,
      respectively, and could be determined reproducibly. With the in vitro digestion
      model, the bioaccessibilities of aflatoxin B(1) and ochratoxin A in the presence
      of four different absorption modulators were in five out of six situations in
      accordance with the in vivo effects in humans and animals. By determining the
      effect of chlorophyllin on the transport of aflatoxin B(1) across the intestinal
      Caco-2 cells, also the sixth combination was in agreement with data in humans.
      Hence, the in vitro digestion model, combined with Caco-2 cells, is a powerful
      experimental tool, which can aid to a more accurate risk assessment of ingested
      contaminants.

PMID- 15582194
TI  - Concentrations and health risk of polycyclic aromatic hydrocarbons in tea.
AB  - Sixteen polycyclic aromatic hydrocarbons (PAHs) were simultaneously measured in 8
      brands of tea and in infusions of one brand of black tea. It was observed that
      the total contents of the 16 PAHs (summation PAHs) in the tea samples ranged from
      323 to 8800 microg/kg with the highest summation PAHs found in a black tea. PAHs
      (3-4 rings) were dominant in all tea samples, with a contribution of 77.7-98.7%
      of the summation PAHs. Infusion times from 10 to 120 min were studied during
      which 3.03-7.69% of the total PAHs contained in the black tea was released into
      the liquor. The percentages of PAHs released (RR) from the tea into the liquor
      were inversely proportional to the lgK(ow) of the PAHs with a mean formula of
      RR=261.7/lgK(ow)-41.32 and R=0.899. To analyze the potential health risk,
      sanitary standards of the 16 PAHs for tea leaves were calculated to be 0.1-110
      mg/kg and the daily PAHs intake from the black tea was calculated to be 6.36
      microg per person.

PMID- 15582195
TI  - Mutagenicity evaluation of the commercial product CI Disperse Blue 291 using
      different protocols of the Salmonella assay.
AB  - Textile dyes can enter the water ecosystem through wastewater discharges
      potentially exposing humans through the consumption of water and food. The
      commercial disperse dye product CI Disperse Blue 291 containing the
      aminoazobenzene 2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)-4
      methoxyacetanilide (CAS registry no. 56548-64-2) was tested for mutagenic
      activity in the Salmonella assay. We used strains with different levels of
      nitroreductase and O-acetyltransferase (i.e., TA98DNP6, YG1024, and YG1041) that
      are relevant enzymes in the activation of nitrocompounds by the intestinal
      microflora. The commercial product tested also was mutagenic for TA1537, TA1538,
      TA98 and TA100. Presence of the pKM101 plasmid and the addition of S9 enhanced
      the mutagenic response. Specialized strains showed that both nitroreductase and O
      acetyltransferase are important in activation of the product. The highest potency
      obtained was 240 revertants per microgram for YG1041 in the presence of S9.
      Besides being able to cause frameshift mutations (hisd3052), the dye was able to
      cause all types of base pair substitution with a preference for TA to AT; CG to
      TA and CG to AT changes. With these results clearly showing that the bacterial
      nitroreductase and O-acetyltransferase metabolites of this compound are
      mutagenic, there is a need to test this dye using in vivo systems to verify
      possible adverse effects of this product in mammalian tissues.

PMID- 15582196
TI  - Biochemical study on the hypoglycemic effects of onion and garlic in alloxan
      induced diabetic rats.
AB  - The present study was carried out to investigate the effects of onion (Allium
      cepa Linn) and garlic (Allium sativum Linn) juices on biochemical parameters,
      enzyme activities and lipid peroxidation in alloxan-induced diabetic rats.
      Alloxan was administered as a single dose (120 mg/kg BW) to induce diabetes. A
      dose of 1 ml of either onion or garlic juices/100 g body weight (equivalent to
      0.4 g/100 g BW) was orally administered daily to alloxan-diabetic rats for four
      weeks. The levels of glucose, urea, creatinine and bilirubin were significantly
      (p<0.05) increased in plasma of alloxan-diabetic rats compared to the control
      group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate
      dehydrogenase (LDH), and alkaline and acid phosphatases (AlP, AcP) activities
      were significantly (p<0.05) increased in plasma and testes of alloxan-diabetic
      rats, while these activities were decreased in liver compared with the control
      group. Brain LDH was significantly (p<0.05) increased. The concentration of
      thiobarbituric acid reactive substances and the activity of glutathione S
      transferase in plasma, liver, testes, brain, and kidney were increased in alloxan
      diabetic rats. Treatment of the diabetic rats with repeated doses of either
      garlic or onion juices could restore the changes of the above parameters to their
      normal levels. The present results showed that garlic and onion juices exerted
      antioxidant and antihyperglycemic effects and consequently may alleviate liver
      and renal damage caused by alloxan-induced diabetes.

PMID- 15582197
TI  - A comparative study of the sensitivity of the 3-induction and 9-induction Buehler
      test procedures for assessing skin sensitisation potential.
AB  - Assessment of skin sensitization potential is a mandatory requirement for the
      registration or notification of most types of chemicals and products. Until
      recently, two methods using the guinea pig as test model were the most widely
      accepted; the guinea pig maximisation test and the Buehler test. In the case of
      agrochemical formulations, which constitute the final end use product in contact
      with operators, industry and also some regulatory authorities consider the
      Buehler method more appropriate as the methodology is more relevant to likely
      exposure in the field. However, certain European regulatory authorities have
      become concerned about the sensitivity of the Buehler test for this purpose and
      have requested that a modified method is used in which additional applications of
      test materials are used during the induction phase of the protocol (a total of 9
      rather than the normal 3). This study was designed to assess whether this
      modification was justified. Six reference substances (formaldehyde, alpha
      hexylcinnamaldehyde, fragrance mix, thimerosal, mercaptobenzothiazole and
      phthalic anhydride); all mild to moderate skin sensitizing chemicals, were
      assessed in a study, which compared the use of 3 and 9 induction applications.
      The results of this study demonstrated that, although most of these sensitisers
      were detected by both protocols, the modified method (9 induction applications)
      was no more sensitive than the standard method (3 induction applications). As the
      modified protocol is also potentially more stressful to the animals, it is
      concluded that the use of additional induction applications in the Buehler test
      cannot be justified from either a scientific or an animal welfare perspective.

PMID- 15582198
TI  - Subchronic mercury treatment of rats in different phases of ontogenesis:
      functional effects on the central and peripheral nervous system.
AB  - Electrophysiological changes caused by inorganic mercury administration during
      the pre- and/or postnatal development were studied. Pregnant female Wistar rats
      were treated, by gavage, with 0.4, 0.8 or 1.6 mg/kg mercury (HgCl2 diluted in
      distilled water): 1/ from day 5 to 15 during pregnancy (P protocol); 2/ from day
      5 to 15 of pregnancy+for 4 weeks of lactation (P+L protocol); 3/ from day 5 to 15
      of pregnancy+for 4 weeks of lactation, and the offspring were further treated for
      8 weeks post-weaning (P+L+P protocol). Electrophysiological parameters
      (electrocorticogram, cortical evoked potentials, conduction velocity and
      refractory periods of peripheral nerve) of the male offspring from dams in the
      groups treated according to the above protocols were investigated at the age of
      12 weeks. The rats' spontaneous and evoked electrophysiological activity
      underwent dose- and treatment-dependent changes following the treatment
      (increased frequency of spontaneous activity, lengthened latencies and duration
      of evoked potentials, lower conduction velocity of the peripheral nerve, etc.).
      In the same rats, however, the treatment failed to cause major signs of general
      intoxication. The results emphasize the functional neurotoxic risk arising from
      the continuous presence of inorganic mercury in the human environment, and point
      to possible use of early functional changes for monitoring the effects of
      mercury.

PMID- 15582199
TI  - Bile acid induced gene expression in LT97 colonic adenoma cells.
AB  - LT97 human colonic adenoma cells reflecting early premalignant genotype and
      growth characteristics have been posed to tumor promoting bile acids in order to
      identify marker genes that permit identification of tumor promoters in vitro.
      Physiologically relevant concentrations of desoxycholate (DOC) and
      chenodesoxycholate (CDC) upregulated expression of c-fos and COX-2 in a
      concentration- and time-dependent manner. Transient induction of c-fos was seen
      with the non-promoting taurodesoxycholate (TDOC) as well as DOC, however extended
      induction at 3 h was only achieved by DOC and CDC reaching 3-6-fold as compared
      to the control. Stimulation of COX-2 expression was completely specific for the
      tumor promoting analogs DOC and CDC. It was about 4-fold in the 80 microM DOC and
      CDC groups after 3 h and increased to 12- and 7-fold respectively after 6 h.
      Expression of VEGF was stimulated 4-5-fold in the tumor promoter (DOC and CDC)
      groups and about 2-fold in the non-promoting controls TDOC and GCDC. At later
      times the tumor promoter specific difference was lost. Our results show that all
      three genes are modulated in a tumor promoter dependent way and that their
      upregulation in LT97 adenoma cells can be used for in vitro testing of colon
      tumor promoters and chemopreventive compounds.

PMID- 15582200
TI  - Evaluation of the anti-genotoxicity of leaf extract of Ashwagandha.
AB  - We have undertaken the studies to investigate the presence of various activities
      of the leaf extract of Ashwagandha (Lash), a commonly used shrub in Indian
      traditional medicine, Ayurveda. In the present study, we studied the effect of
      Lash against MNNG-induced genotoxicity in onion root tip cells. We report that
      Lash offered substantial protection against the mutagenic effects of MNNG.

PMID- 15582201
TI  - Ameliorative effects of black tea extract on aflatoxin-induced lipid peroxidation
      in the liver of mice.
AB  - We have evaluated the ameliorative effect of black tea extract on aflatoxin
      induced lipid peroxidation in the liver of mice. Adult male albino mice were
      orally administered with 25 and 50 microg of aflatoxin in 0.2 ml olive
      oil/animal/day for 30 days. Results revealed dose-dependent and significantly
      (p<0.05) higher lipid peroxidation in the liver of aflatoxin-treated mice than
      that of vehicle control. As compared with vehicle control, the levels of non
      enzymatic antioxidants such as glutathione and ascorbic acid, as well as the
      enzymatic antioxidants such as superoxide dismutase, glutathione peroxidase and
      catalase were significantly (p<0.05) lowered in the liver of aflatoxin-treated
      mice. Oral administration of two percent aqueous black tea extract along with
      aflatoxin for 30 days (groups 6 and 7) caused significant (p<0.05) amelioration
      in aflatoxin-induced lipid peroxidation by increasing significantly (p<0.05) the
      activities of enzymatic (superoxide dismutase, glutathione peroxidase, catalase)
      and contents of non-enzymatic (glutathione and ascorbic acid) antioxidants in the
      liver of mice as compared with those given aflatoxin alone (groups 4 and 5).
      Thus, oral administration of black tea along with aflatoxin significantly
      (p<0.05) ameliorates aflatoxin-induced lipid peroxidation in the liver of mice.

PMID- 15582202
TI  - Assessment of dietary intake of flavouring substances within the procedure for
      their safety evaluation: advantages and limitations of estimates obtained by
      means of a per capita method.
AB  - The procedure for the safety evaluation of flavourings adopted by the European
      Commission in order to establish a positive list of these substances is a
      stepwise approach which was developed by the Joint FAO/WHO Expert Committee on
      Food Additives (JECFA) and amended by the Scientific Committee on Food. Within
      this procedure, a per capita amount based on industrial poundage data of
      flavourings, is calculated to estimate the dietary intake by means of the
      maximised survey-derived daily intake (MSDI) method. This paper reviews the MSDI
      method in order to check if it can provide conservative intake estimates as
      needed at the first steps of a stepwise procedure. Scientific papers and opinions
      dealing with the MSDI method were reviewed. Concentration levels reported by the
      industry were compared with estimates obtained with the MSDI method. It appeared
      that, in some cases, these estimates could be orders of magnitude (up to 5) lower
      than those calculated considering concentration levels provided by the industry
      and regular consumption of flavoured foods and beverages. A critical review of
      two studies which had been used to support the statement that MSDI is a
      conservative method for assessing exposure to flavourings among high consumers
      was performed. Special attention was given to the factors that affect exposure at
      high percentiles, such as brand loyalty and portion sizes. It is concluded that
      these studies may not be suitable to validate the MSDI method used to assess
      intakes of flavours by European consumers due to shortcomings in the assumptions
      made and in the data used. Exposure assessment is an essential component of risk
      assessment. The present paper suggests that the MSDI method is not sufficiently
      conservative. There is therefore a clear need for either using an alternative
      method to estimate exposure to flavourings in the procedure or for limiting
      intakes to the levels at which the safety was assessed.

PMID- 15582203
TI  - Xanthorrhizol has a potential to attenuate the high dose cisplatin-induced
      nephrotoxicity in mice.
AB  - Cisplatin is a widely used anticancer drug, but it can produce undesirable side
      effects such as nephrotoxicity. The present study investigated the effect of
      xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) on
      cisplatin-induced nephrotoxicity in mice. A single dose of cisplatin (45 mg/kg,
      i.p.) significantly elevated the levels of blood urea nitrogen, serum creatinine,
      and the kidney to body weight ratio, but the pretreatment of xanthorrhizol (200
      mg/kg/day, per os) for 4 days significantly attenuated the cisplatin-induced
      nephrotoxicity. The preventive effect of xanthorrhizol was more efficacious than
      that of curcumin with the same amount (200 mg/kg). However, this effect seemed
      not to be related with the ability of xanthorrhizol to regulate the DNA-binding
      activities of transcription factors such as nuclear factor-kappaB (NF-kappaB) and
      activator protein 1 (AP-1). This is first time the preventive effect of
      xanthorrhizol on cisplatin-induced nephrotoxicity has been demonstrated, and
      these data suggest that the administration of xanthorrhizol is a promising
      approach in the treatment of nephrotoxicity caused by cisplatin.

PMID- 15582204
TI  - Inhibition of sphingolipid biosynthesis decreases phosphorylated ERK2 in LLC-PK1
      cells.
AB  - Fumonisin B(1) (FB(1)) is a fungal toxin produced by Fusarium verticillioides
      that inhibits ceramide synthase (CS), a key enzyme in the de novo sphingolipid
      biosynthesis pathway. In LLC-PK(1) cells, FB(1) inhibits cell proliferation and
      induces apoptosis, which can be prevented by inhibitors of serine
      palmitoyltransferase (SPT). Inhibition of SPT prevents the FB(1)-induced
      accumulation of free sphinganine, a precursor of ceramide biosynthesis. However,
      not all of the effects of FB(1) in LLC-PK(1) cells can be explained solely by the
      increase in free sphingoid bases. The downstream signaling pathways that are
      affected by FB(1)-induced disruption of sphingolipid biosynthesis are not well
      understood. This study determined, in LLC-PK(1) cells, changes in p42 MAP kinase
      (phosphorylated ERK2 [pERK2]) phosphorylation in response to various inhibitors
      of key enzymes of the de novo sphingolipid biosynthesis pathway (CS, SPT, and
      glucosylceramide synthase [GlcCer synthase]). The results show that inhibition of
      any of the three enzymes caused a similar decrease in the extent of
      phosphorylation of ERK2 with no reduction in total ERK2. The co-treatment of
      FB(1) (CS inhibitor) with SPT inhibitors or the GlcCer synthase inhibitor had no
      effect on the FB(1)-induced reduction in pERK2 phosphorylation, indicating that
      FB(1)-mediated changes in phosphorylation of pERK2 was independent of increases
      in free sphinganine or its metabolites or a reduction in ceramide. Nonetheless,
      the decrease in pERK2 phosphorylation was dependent on inhibition of de novo
      sphingolipid biosynthesis. Decreased pERK2 activity could contribute to the
      physiological effects of FB(1) in LLC-PK(1) cells that are not due to alteration
      in pathways modulated by free sphingoid bases and their metabolites but are
      sensitive to inhibition of glycosphingolipid biosynthesis.

PMID- 15582205
TI  - Increased plasma creatine kinase activities triggered by edible wild mushrooms.
AB  - The consumption of wild mushrooms is mostly based on tradition and not scientific
      evidence. Recently the widely consumed Tricholoma flavovirens caused delayed
      rhabdomyolysis in humans. In this study, 42 mice and 4 humans consumed T.
      flavovirens mixed with regular food items. In mice, the plasma creatine kinase
      activity increased at 9 g kg(-1)day(-1). However, the same was observed with the
      well-known and commercially important Boletus edulis. The observed effect is
      probably not species-specific but represents an unspecific response and requires
      individual sensitivity and a great amount of ingested mushroom to manifest
      itself. A screening program of wild mushrooms is recommended to clarify how
      widespread this effect is.

PMID- 15582206
TI  - Induction of apoptosis by fatty acid ethyl esters in HepG2 cells.
AB  - Fatty acid ethyl esters (FAEEs) are esterification products of ethanol and fatty
      acids which have been found particularly in the organ damaged by ethanol abuse.
      To evaluate any effect of FAEEs on HepG2 cells, we added FAEEs to cell culture
      medium. Electrophoresis of DNA from HepG2 cells exposed to 18.5 microM ethyl
      palmitate (EP) and 10.6 microM ethyl stearate (ES) for 24 h revealed a smear
      which is typical of non-specific degradation by DNA ladder assay. Apoptosis was
      characterized by electron microscopy, flow cytometry revealed that the cell cycle
      of HepG2 cells was perturbed by exposure to FAEEs. In the present study we
      demonstrate that treatment of HepG2 cells with EP and ES induces apoptosis, as
      well as perturbing the cell cycle as the number of cells in the G(2)/M and S
      phases decreased.

PMID- 15582207
TI  - In vivo DNA damaging potential of sanguinarine alkaloid, isolated from argemone
      oil, using alkaline Comet assay in mice.
AB  - Consumption of mustard oil contaminated with argemone oil is well known to cause
      clinical manifestation referred to as "Epidemic Dropsy". Our prior studies have
      shown that argemone oil produces genotoxic effects in mice [Ansari, K.M., et al.,
      2004. Int. J. Cancer 112, 890]. Since, sanguinarine alkaloid is the major
      component of argemone oil, the in vivo DNA damaging potential of the isolated
      alkaloid was investigated in blood and bone marrow cells of mice using alkaline
      Comet assay. Swiss albino male mice were given single intraperitoneal
      administration of 1.35, 2.70, 5.40, 10.80 and 21.60 mg sanguinarine alkaloid/kg b
      wt., while controls were treated with saline in the same manner. The results
      revealed a dose dependent increase in DNA damage in blood and bone marrow cells
      following 24 h treatment of sanguinarine alkaloid. All the three parameters of
      Comet assay including olive tail moment (OTM), tail length and tail DNA showed
      significant (p<0.05) increases in blood and bone marrow cells at respective doses
      of 10.80 and 5.40 mg alkaloid/kg b wt. However, some of the parameters were
      significantly increased even at lower doses of sanguinarine alkaloid (2.70 mg/kg
      b wt.). The frequency of cells exhibiting greater DNA damage were found to be
      increased by sanguinarine alkaloid in a concentration dependent manner. These
      results indicate that single exposure of sanguinarine alkaloid causes DNA damage
      in blood and bone marrow cells of mice, which could be responsible for the
      genotoxicity of argemone oil.

PMID- 15582208
TI  - Eye irritation of low-irritant cosmetic formulations: correlation of in vitro
      results with clinical data and product composition.
AB  - Alternative methods to the Draize eye irritation test, such as the hen's egg test
      chorioallantoic membrane (HET-CAM) or the bovine corneal opacity and permeability
      (BCOP) tests, are currently used to evaluate the irritant potential of cosmetic
      or consumer products. Although, for strong irritants, the results of these tests
      correlate well with those of the Draize test, they appear to be less suited to
      identify mild irritants. In order to improve the sensitivity of alternative eye
      irritation tests, we developed a novel method that uses a human corneal
      epithelial cell line (CEPI), and the endpoints of cytotoxicity and IL-8 release.
      Twelve make-up removers were assessed by the HET-CAM, BCOP and CEPI tests, as
      well as in a clinical in-use test under ophthalmological control after their
      application to the external eye lid. In addition, we investigated the impact of
      osmolality and raw material composition on in vitro and clinical results and
      compared the in vitro results with those of clinical studies. Overall, although
      HET-CAM results were unrelated to eye discomfort and adverse clinical signs, they
      correlated mainly with the presence and concentration of surfactants in the test
      articles. BCOP scores were unrelated to clinical signs, but related mainly to
      glycol and sodium lactate content and concentration in the test articles.
      Cytotoxicity in CEPI mainly correlated with presence and concentrations of
      surfactants, and IL-8 release to clinical signs and/or glycol and sodium lactate
      concentrations. Overall, IL-8 release appeared to be the most sensitive and
      reliable endpoint to predict human eye tolerance to mildly irritant products.
      Although our results suggest that the IL-8 assay appears to be a promising screen
      for borderline-irritant formulations, further experiments are required to confirm
      and validate these preliminary results.

PMID- 15582209
TI  - Effects of subcutaneous administration of daidzein on blastocyst implantation in
      rats.
AB  - The study was conducted to investigate the effects of phytoestrogen daidzein on
      blastocyst implantation in rats. Following successful mating, female rats were
      given daidzein by subcutaneous administration at the dose of 0 (vehicle control,
      n=15), 50 mg/kg body weight (n=15) and 150 mg/kg body weight (n=15) daily on day
      1-7 of pregnancy and were sacrificed on day 8 of gestation. The results revealed
      that high-dose treatment (150 mg/kg body weight) significantly diminished the
      rate of blastocyst implantation and serum levels of gonadotropin-releasing
      hormone (GnRH), progesterone, and gonadotropins (FSH and LH), meanwhile the serum
      level of beta endorphin increased significantly. These effects were not observed
      in the low-dose treatment group (50 mg/kg body weight). The results of this study
      suggested that the anti-implantation effects of daidzein are probably caused by
      the interference of the hypothalamus-pituitary-gonadal axis which is involved in
      the implantation process.

PMID- 15582210
TI  - CYP superfamily perturbation by diflubenzuron or acephate in different tissues of
      CD1 mice.
AB  - This work aimed to investigate whether the insecticide acephate (125 or 250 mg/kg
      b.w.) or diflubenzuron (752 or 1075 mg/kg b.w.), two of the most widely used
      pesticides worldwide, impairs CYP-linked murine metabolism in liver, kidney and
      lung microsomes after repeated (daily, for three consecutive days) i.p.
      administration. The regio- and stereo-selective hydroxylation of testosterone was
      used as multibiomarker of different CYP isoforms. Both gender and tissue specific
      effects were observed. Lung was the most responsive tissue to induction by lower
      diflubenzuron dose, as exemplified by the marked increase of testosterone 7alpha
      hydroxylation (CYP2A) (up to 13-fold) in males. Higher dose produced a
      generalized inactivation. At the lower dose acephate induced 6beta- (CYP3A1/2,
      liver) as well as 2beta- (CYP2B1/2, kidney) hydroxylase activities (
      approximately 5 and approximately 4-fold increase, respectively) in males. In
      females, a marked suppression of the various hydroxylations was observed. At 250
      mg/kg of acephate, animals did not survive. Induction of the most affected
      isoforms was sustained by immunoblotting analysis. Corresponding human CYP
      modulations might disrupt normal physiological functions related to these
      enzymes. Furthermore, the co-mutagenic and promoting potential of these
      pesticides, phenomena linked to CYP upregulation (e.g. increased bioactivation of
      ubiquitous pollutants and generation of oxygen free radicals) are of concern for
      a more complete definition of their overall toxicological potential.

PMID- 15582211
TI  - [SOFCEP editorial].

PMID- 15582212
TI  - [Face lifts complications].

PMID- 15582213
TI  - [Rhytidectomy and Raynaud's phenomenon: about two cases].
AB  - Raynaud's phenomenon is a currently vascular syndrome (8 to 10% of women and 3 to
      5% of men). It was defined as episodic ischaemia of the fingers, toes, nose, ears
      and nipples, which presents clinically as pallor, cyanosis, and often rubor of
      the skins, in response to cold, emotional stimuli and vasoconstriction agents.
      The phenomenon is caused by a vasoconstriction of arterials skin. In severe forms
      of the phenomenon, we can see ulcerations and necrosis. We report here two cases
      of rhytidectomy flap necrosis in Raynaud's Phenomenon. After review of
      literature, we explain the elements of physiopathology whose can explain these
      complications and we try to establish recommendations to these complications.

PMID- 15582214
TI  - [Aesthetic blepharoplasties, complications and treatment].

PMID- 15582215
TI  - [Unfavorable rhinoplasty results].

PMID- 15582216
TI  - [Abdominoplastic complications].

PMID- 15582217
TI  - [Bodylift complications].

PMID- 15582218
TI  - [Internal faces lifting legs complications].

PMID- 15582219
TI  - [Liposuction's complications].

PMID- 15582220
TI  - [Complications of autografting].

PMID- 15582221
TI  - [The legal management of cosmetic surgery complications].

PMID- 15582222
TI  - Protein quality control in Alzheimer's disease by the ubiquitin proteasome
      system.
AB  - The ubiquitin proteasome system (UPS) is the major protein quality control system
      in eukaryotic cells. Many neurodegenerative diseases are characterized by
      aggregates and inclusions of aberrant proteins, implying a sub-optimal
      functioning or defective UPS. The last few years have seen increasing evidence
      for the involvement of the UPS in neurodegenerative disorders, including
      Alzheimer's disease (AD). Notably, decreases in proteasome activity were detected
      in several cortical areas in AD patients. In addition, proteins that accumulate
      in the classical hallmarks of AD were linked to UPS function. This review
      specifically discusses the involvement of the UPS in AD pathogenesis. First, a
      detailed overview of the UPS is presented, after which AD pathology and its
      relation to the UPS is discussed.

PMID- 15582223
TI  - Metabotropic glutamate receptors and striatal synaptic plasticity: implications
      for neurological diseases.
AB  - Long- and short-term changes in the efficacy of synaptic transmission are known
      as synaptic plasticity. Phenomena such as long-term depression (LTD) and long
      term potentiation (LTP) are two classical forms of synaptic plasticity that are
      expressed in several brain areas, including the striatum. Bi-directional changes
      in corticostriatal synaptic transmission, i.e. LTD and LTP, have been proposed to
      represent the cellular mechanisms underlying the physiological processes of motor
      learning and behavior. In parallel, other forms of synaptic plasticity induced by
      different experimental pathological conditions have been described in the
      striatum; these changes are presumed to represent the cellular processes
      underlying several neurological disorders, including Parkinson's disease and
      Huntington's chorea. A considerable number of receptor and post-receptor systems
      participate in the mechanisms of synaptic plasticity in the striatum, where
      glutamate plays a primary role through its ionotropic and metabotropic receptors
      (mGluRs). These latter constitute a group of recently characterized molecules,
      which have been shown to modulate synaptic transmission by acting on cellular
      excitability, ionic conductances and neurotransmitter release. These receptors
      have also been involved in several neuronal pathophysiological processes. The
      role of mGluRs in synaptic transmission and synaptic plasticity has been recently
      deeply studied and characterized in the striatum, in both physiological and
      pathological conditions. These findings open new and interesting perspectives in
      the study of basal ganglia function, and introduce new possible pharmacological
      approaches for the treatment of neurological disorders in which mGluRs have been
      experimentally involved.

PMID- 15582224
TI  - Mesolimbic dopaminergic pathways in fear conditioning.
AB  - One of the most common paradigms used to study the biological basis of emotion,
      as well as of learning and memory, is Pavlovian fear conditioning. In the
      acquisition phase of a fear conditioning experiment, an emotionally neutral
      conditioned stimulus (CS)--which can either be a discrete stimulus, such as a
      tone, or a contextual stimulus, such as a specific environment--is paired with an
      aversive unconditioned stimulus (US), for example a foot shock. As a result, the
      CS elicits conditioned fear responses when subsequently presented alone during
      the expression phase of the experiment. While considerable work has been done in
      relating specific circuits of the brain to fear conditioning, less is known about
      its regulation by neuromodulators; the understanding of which would be of
      therapeutic relevance for fear related diseases such as phobia, panic attacks,
      post traumatic stress disorder, obsessive compulsive disorder, or generalized
      anxiety disorder. Dopamine is one of the neuromodulators most potently acting on
      the mechanisms underlying states of fear and anxiety. Recently, a growing body of
      evidence has suggested that dopaminergic mechanisms are significant for different
      aspects of affective memory, namely its formation, expression, retrieval, and
      extinction. The aim of this review is to clarify the complex actions of dopamine
      in fear conditioning with respect to the wide-spread distribution of dopaminergic
      innervation over structures constituting the fear related circuitry. A particular
      effort is made to understand how dopamine in the amygdala, medial prefrontal
      cortex and nucleus accumbens--target structures of the mesolimbic dopamine system
      originating from the ventral tegmental area--could relate to different aspects of
      fear conditioning.

PMID- 15582225
TI  - Cell size relations for sonolysis.
AB  - The occurrence of cell lysis following exposure to ultrasound (US) has been well
      documented; the specifics of the mechanistic process(es) involved have proven to
      be difficult to characterize. There appear to be two major mechanisms of US
      induced cell lysis in vitro, acoustic cavitation and bubble transport. Both
      involve shear forces. Earlier research showed that the size of oil droplets was a
      crucial factor in their rupture by shear forces; the greater the size the greater
      the rupture per unit shear force. Here we find further support (Miller et al.
      2000, 2001a, 2003a; Miller and Battaglia 2003; Abramwocz et al. 2003) that, under
      a number of experimental US conditions causing hemolysis in vitro, cell volume
      (i.e., size) is an apparently critical factor.

PMID- 15582226
TI  - An experimental characterization of elastographic spatial resolution: analysis of
      the trade-offs between spatial resolution and contrast-to-noise ratio.
AB  - An experimental study of the spatial resolution in elastography was conducted.
      Models that involved two cylindrical inclusions arranged as a wedge were used to
      characterize the axial and lateral resolution of the axial strain elastograms. A
      study of the dependence of the spatial resolution on several factors such as the
      algorithmic parameters, the applied strain and the modulus contrast was
      performed. The axial resolution was found to show a linear dependence with
      respect to the algorithmic parameters, namely the window length and the window
      shift used for strain estimation. The lateral resolution showed a weak dependence
      on the algorithmic parameters. A weak dependence of the spatial resolution on
      factors such as the modulus contrast and the applied strain was found. The trade
      offs between the spatial resolution and the elastographic contrast-to-noise ratio
      (CNR(e)) were then analyzed. A nonlinear trade-off between the CNR(e) and the
      axial and lateral resolution was shown for conventional strain estimation
      techniques, with the CNR(e) improving at a more than linear rate with respect to
      a linear degradation in the resolution. This study provided an experimental
      framework for characterizing the spatial resolution in elastography and
      facilitating a comparison of the CNR(e) with spatial resolution.

PMID- 15582227
TI  - Effect of shell type on the in vivo backscatter from polymer-encapsulated
      microbubbles.
AB  - This study compared in vivo enhancement from four different polymer-encapsulated
      ultrasound (US) contrast agents. The agents were produced with a rigid shell
      composed of the biodegradable block copolymer poly[D,L-lactide-co-glycolide]
      (PLGA) with the lactic and glycolic acid ratios 50:50, 75:25, 85:15 and 100:0
      (i.e., increasingly hydrophobic shell compositions). Approximately the same
      bubble diameter (1.2 microm) and concentration (0.4 g/mL) were obtained for each
      agent. In four rabbits, audio Doppler signals were acquired from a 10 MHz cuff
      transducer placed around a surgically exposed vessel (contrast dose: 0.0125 to
      0.15 mL/kg). In vivo dose responses were calculated off-line (in dB). Nine rabbit
      kidneys were imaged during contrast administration (0.1 mL/kg) in power Doppler
      and grey-scale pulse inversion harmonic (PIHI) modes using an HDI 5000 scanner
      (Philips Medical Systems, Bothell, WA). Time-intensity curves were produced and
      the time-to-peak, peak intensity, slope, area under the curve (AUC) and total
      duration of enhancement for each agent were compared. All agents produced marked
      Doppler enhancement with increasing duration from the 50:50 agent (48 +/- 10 s)
      to the 75:25 agent (166 +/- 46 s), the 85:15 agent (403 +/- 83 s) and with the
      100:0 agent (603 +/- 93 s) lasting longest (p < 0.02). No other parameters
      changed significantly, except the AUC of the 85:15 agent, which was greater than
      that of the 50:50 agent (190.75 vs. 61.58; p = 0.02). The in vivo dose-response
      curves were similar for all agents, with mean enhancement up to 20.6 +/- 1.11 dB
      (p = 0.17). In conclusion, contrast duration increases by an order of magnitude
      as the lactic acid component in the polymer-encapsulated bubbles increases and
      the shell, thus, becomes increasingly hydrophobic.

PMID- 15582228
TI  - Excess risk thresholds in ultrasound safety studies: statistical methods for data
      on occurrence and size of lesions.
AB  - Concerns about the safe use of clinical ultrasound (US) at diagnostic pressure
      levels (below a mechanical index, or MI, = 1.9) have stimulated considerable
      research in US risk assessment. The objective of the present study was to develop
      probability-based risk thresholds for US safety studies, to present statistical
      methods for estimating the thresholds and their standard errors and to compare
      these methods with the analysis based on a piecewise linear ("hockey stick")
      model. The excess risk at exposure level x > 0 was defined as the relative
      increase in the probability of a lesion at that level compared with the
      background probability of a lesion at exposure x = 0. The risk threshold was then
      defined as the exposure level at which the excess risk exceeded a specified level
      (e.g. 5% or 50%). Thus, given pressure-dependent estimates of the excess risk,
      the thresholds were estimated by solving the risk equation to obtain the pressure
      at which the target level of excess risk occurs. Threshold estimates of this type
      have been developed extensively in the literature for incidence (presence or
      absence) data. Only recently, however, have excess risk threshold estimates been
      derived for data in which lesion size (depth, surface area) is measured if
      present and a zero is recorded if the lesion is absent. Tobit regression was used
      to estimate pressure-dependent percentiles of the size distribution, and the
      excess risks were estimated from the tobit probability of a positive-valued
      response. The tobit model provides a well-established approach to modeling data
      constrained to be nonnegative. Solving the risk equation for the tobit model
      leads to risk threshold estimates that incorporate the information on size of
      observed lesions. Results using these probability-based risk estimates were
      compared with results for a piecewise linear ("hockey stick") model, which has
      also been used in the US safety literature, although it does not explicitly
      address the nonnegativity constraint in the sampling model. The comparisons were
      carried out for data from two previously published studies, from different
      laboratories, on US-induced lung hemorrhage. The thresholds derived from logistic
      regression of lesion occurrence and tobit regression of lesion size were quite
      consistent with each other and within sampling error. The hockey stick
      thresholds, defined as the exposure level at which the piecewise linear model for
      the probability of the expected size of a lesion bends upward, corresponded to
      quite different excess risk values for incidence (lesion occurrence) compared
      with size (lesion surface area or depth), although these methods have been
      developed previously for both types of data. The use of probability-based excess
      risk thresholds is recommended to obtain consistent incidence vs. size thresholds
      and to ensure that the thresholds are well-defined and interpretable independent
      of the details of the statistical model.

PMID- 15582229
TI  - Simulation study of effects of speed of sound and attenuation on ultrasound
      lateral resolution.
AB  - Experiments have shown that the lateral profile of a point target measured with a
      clinical ultrasound scanner is wider when the target is embedded in a urethane
      phantom than when it is in a traditional gel phantom. The behavior has been
      attributed to the low speed of sound in the urethane material, with the
      possibility that some of the broadening is caused by increased attenuation in
      this material. In this paper we apply a computer simulation model to study this
      behavior. Lateral beam profiles modeled for targets within a medium having a
      speed of sound and an attenuation matching that of urethane are compared with
      profiles for targets in a water-based gel. Simulations yield results that agree
      qualitatively with published experimental results. The lateral profile broadening
      in urethane is caused by the 6 % mismatch between speed of sound in this material
      and the speed of sound assumed in the receive focusing and beam forming.
      Attenuation plays a lesser role than the mismatch of the speed of sound.

PMID- 15582230
TI  - Developmental changes in integrated ultrasound backscatter from embryonic blood
      in vivo in mice at high US frequency.
AB  - Mouse blood imaged using high-frequency ultrasound (US) is more echogenic in
      embryos than in adults. Studying changes in blood echogenicity in embryos may be
      of fundamental interest in studies on the genetic regulation of normal and
      abnormal blood development in mutant mice. Embryonic red blood cells (RBCs) are
      large and nucleated in midgestation but decrease in size and become enucleated as
      they mature. We therefore hypothesised that these structural alterations are
      responsible for variations in echogenicity of embryonic blood with gestational
      age and development. The objective of the current study was to quantify these
      structural changes in echogenicity (echo brightness) and apparent integrated
      backscatter (AIB) from embryonic blood at high US frequencies in vivo in mice.
      Results from anaesthetised pregnant mice studied using transcutaneous US showed
      that echogenicity of embryonic blood in the heart, aorta and umbilical cord and
      AIB within the heart chambers peaked at embryonic day (ED) 13.5 and then
      decreased progressively toward term. Between EDs 13.5 and 17.5 (near term), RBC
      mean cell volume decreased from 133 to 109 fL, haematocrit increased from 12 to
      34%, and the percentage of nucleated RBCs decreased from 59 to 2%. Relative to
      younger ages, RBC nuclei at ED 13.5 were small and dense (pyknotic) which may
      have contributed to the peak in echogenicity and AIB at this age. To calculate
      the AIB, radiofrequency (RF) signals with centre frequencies of 28 MHz and 35 MHz
      were integrated over the 16- to 35-MHz and 21- to 42-MHz frequency range,
      respectively. At 28 MHz, mean apparent integrated backscatter of blood in the
      embryonic heart increased significantly from 0.0023 +/- 0.0004 Sr.cm(-1) (mean +/
      SEM) at ED 12.5 to peak at 0.0037 +/- 0.0005 Sr.cm(-1) at ED 13.5. The mean AIB
      then decreased progressively with advancing gestation to 0.0002 +/- 0.0001 Sr.cm(
      1) at ED 17.5. At 35 MHz, the mean AIB changed similarly with gestational age,
      except that values were lower than at 28 MHz at all ages. Higher attenuation of
      US at 35 MHz than at 28 MHz in tissue likely accounted for the lower AIB of blood
      insonified at 35 MHz. We speculate that developmental changes in red cell
      morphology are responsible for the observed changes in echogenicity and AIB of
      embryonic blood with gestational age in mice.

PMID- 15582231
TI  - Feasibility study of ultrasonic fatty liver biopsy: texture vs. attenuation and
      backscatter.
AB  - The objective of this study was to compare textural to attenuation/backscatter
      indices of fatty liver correlated to histology to suggest the better approach for
      an objective noninvasive ultrasonic "biopsy". Forty-four patients with severe
      steatosis by histopathology were selected for this study. Ten patients had "pure"
      fatty liver and 34 had in addition fibrosis and/or inflammation. Ultrasonic
      images were acquired before needle insertion. The ROI used for biopsy was marked
      on the ultrasonic image and characterized by three attenuation/backscatter and 18
      textural related indices. Statistical analysis was performed using logistic
      regression. Twenty-one healthy subjects served as control. The
      attenuation/backscatter indices were superior to textural indices in
      differentiating between the categories studied. Pure fatty livers could be
      reliably identified (AUC = 1, SE = 0). Among the 18 textural indices, "co
      occurrences sum entropy" and "co-occurrences entropy" presented the best results.
      Attenuation/backscatter based indices appear to have better potential than the
      textural based indices.

PMID- 15582232
TI  - Correlations among critical closing pressure, pulsatility index and
      cerebrovascular resistance.
AB  - We attempted to explore the relationships among critical closing pressure (CrCP),
      resistance-area product (RAP) and traditional resistance indices of cerebral
      hemodynamics. Twenty healthy volunteers were studied. Blood pressure was obtained
      with servo-controlled plethysmography. Cerebral blood flow velocity (CBFV) was
      monitored by transcranial Doppler. Hemodynamic changes were induced by
      hyperventilation and by 5% CO(2) inhalation. Beat-to-beat CrCP and RAP values
      were extracted by linear regression analysis of instantaneous arterial blood
      pressure (ABP) and CBFV tracings. Gosling's pulsatility index (PI) and
      cerebrovascular resistance (CVR) were calculated. RAP correlated well with CVR at
      rest and during provocative tests (p = 0.006 approximately <0.001). There was no
      correlation among CrCP, CVR and PI. The changes in CVR correlated with those in
      RAP (p = 0.008 for the 5% CO(2) test and p = 0.014 for the hyperventilation
      test). The changes in PI and CrCP showed significant correlation (p = 0.004 for
      the 5% CO(2) test and p = 0.003 for the hyperventilation test). RAP reliably
      reflected cerebrovascular resistance. The changes in CrCP were valuable in
      assessing cerebrovascular regulation. Estimating changes in CrCP and RAP provided
      better understanding of the nature of cerebrovascular regulation.

PMID- 15582233
TI  - Ultrasound-induced microbubble coalescence.
AB  - We studied the interaction of ultrasound contrast agent bubbles coated with a
      layer of lipids, driven by 0.5 MHz ultrasound. High-speed photography on the
      submicrosecond timescale reveals that some bubbles bounce off each other, while
      others show very fast coalescence during bubble expansion. This fast coalescence
      cannot be explained by dissipation-limited film drainage rates. We conclude that
      the lipid shell ruptures upon expansion, exposing clean free bubble interfaces
      that support plug flow profiles in the film and inertia-limited drainage whose
      time scales match those of the observed coalescence.

PMID- 15582234
TI  - The effect of transducer characteristics on the estimation of Nakagami paramater
      as a function of scatterer concentration.
AB  - The effect of transducer characteristics on the sensitivity of the Nakagami
      parameter to detect the variation of scatterer concentrations was studied. The
      rationale for this study stems from our pilot results which showed that the
      Nakagami parameters, estimated using a nonfocused transducer were not as
      sensitive as those of measurements using a commercial ultrasonic scanner in
      previous reports. This discrepancy may be attributed to the effects of transducer
      characteristics relative to the size of the resolution cell as verified by
      measurements of phantoms and 2-D computer simulations. The Nakagami parameter as
      a function of scatterer concentration was calculated using backscattered signals
      acquired from the scattering medium of different scatterer concentrations ranging
      from 2 to 32 scatterers/mm(3) using both 5 MHz nonfocused and focused
      transducers. Experimental and simulation results obtained from the nonfocused
      transducer represent that their respective Nakagami parameters increased from
      1.17 to 1.31 and from 0.82 to 1.01 corresponding to the increase of scatterer
      concentrations. For the results obtained from the focused transducer, their
      average Nakagami parameters increased from 0.27 to 0.72 and from 0.33 to 0.81.
      These consistent results demonstrated that Nakagami parameter estimated using a
      focused transducer tends to be more sensitive than that by a nonfocused
      transducer to detect the variation of low scatterer concentration. This
      difference is fully due to the effect of transducer characteristics associated
      with the effective number of scatterers in the resolution cell.

PMID- 15582235
TI  - Quantification of perfusion of liver tissue and metastases using a multivessel
      model for replenishment kinetics of ultrasound contrast agents.
AB  - Low-MI (mechanical index) ultrasound allows real-time observation of
      replenishment kinetics after destruction ("flash") of ultrasound contrast agents
      (USCA). We developed an examination protocol and a mathematical model to quantify
      perfusion of liver tissue and hepatic metastases. Using a modified multivessel
      model, we attempted a consistent, physiological description of microbubble
      replenishment in liver tissue. Perfusion parameters were calculated, separately
      for the arterial and portal venous phase of liver perfusion, using an i.v. bolus
      injection of 2 x 2.4 mL SonoVue. The model was evaluated for 10 examinations of
      liver metastases using flash/low-MI imaging. In contrast to the established,
      exponential model, the new model consistently describes the sigmoid replenishment
      of USCA measured in vivo, using flash/low-MI imaging. Parameters for blood
      volume, blood velocity and blood flow in liver tissue and metastases can be
      calculated during the arterial and the portal venous phase after a CA bolus
      injection. The median arterial perfusion in the examined liver metastases was
      more than 2.5 times higher than in normal liver tissue, whereas the median
      perfusion during the portal venous phase was more than five times higher in the
      liver tissue than that in metastases. Microbubble replenishment measured with
      flash/low-MI US techniques can be consistently analyzed using the multivessel
      model, even after a bolus injection of USCA. This allows for the quantification
      of perfusion of liver tissue and hepatic metastases and provides promising
      parameters of tissue viability and tumor characterization.

PMID- 15582236
TI  - Feasibility study: real-time 3-D ultrasound imaging of the brain.
AB  - We tested the feasibility of real-time, 3-D ultrasound (US) imaging in the brain.
      The 3-D scanner uses a matrix phased-array transducer of 512 transmit channels
      and 256 receive channels operating at 2.5 MHz with a 15-mm diameter footprint.
      The real-time system scans a 65 degrees pyramid, producing up to 30 volumetric
      scans per second, and features up to five image planes as well as 3-D rendering,
      3-D pulsed-wave and color Doppler. In a human subject, the real-time 3-D scans
      produced simultaneous transcranial horizontal (axial), coronal and sagittal image
      planes and real-time volume-rendered images of the gross anatomy of the brain. In
      a transcranial sheep model, we obtained real-time 3-D color flow Doppler scans
      and perfusion images using bolus injection of contrast agents into the internal
      carotid artery.

PMID- 15582237
TI  - Quantitative ultrasound at the hand phalanges in pregnancy: a longitudinal study.
AB  - In the prospective study, 48 females in normal pregnancy were evaluated to
      determine if the presence of disturbances of maternal bone and mineral status is
      related to fetal and newborn growth. The aim of the study was to estimate mean
      and individual changes in maternal skeletal and laboratory variables during
      pregnancy and their correlations with fetal and newborn sizes. Maternal bone and
      mineral status was assessed in first, second and third trimester by quantitative
      ultrasound (US), or QUS, at the hand phalanges (Ad-SoS [m/s]) performed by DBM
      Sonic 1200 (IGEA, Carpi, Italy) and laboratory investigations were collected
      (serum total calcium, total alkaline phosphatase and phosphate). The hypothesis
      that fetus growth and sizes of the newborn may have an influence on bone and
      mineral status in pregnancy was tested by the correlation of ultrasonographic
      fetal measurements and newborn sizes with changes in maternal QUS and biochemical
      data. Ad-SoS decreased significantly (p < 0.00001) and alkaline phosphatase
      increased significantly in second and third trimester of pregnancy (p < 0.01). A
      decrease in Ad-SoS greater than least significant change (LSC) was observed in 22
      females (46%) during pregnancy. Changes in alkaline phosphatase correlated
      significantly with changes in Ad-SoS (r = -0.31, p < 0.05). Fetal
      ultrasonographic measurements (femur length and biparietal diameter) correlated
      significantly with changes in alkaline phosphatase (r ranged 0.31 to 0.56, p <
      0.05). No significant correlations were observed between fetal ultrasonographic
      measurements (femur length and biparietal diameter) and newborn size with changes
      in Ad-SoS. In conclusion, the study revealed considerable changes in maternal
      bone and mineral status in normal pregnancy.

PMID- 15582238
TI  - Power Doppler ultrasound imaging for quantification of urinary bladder neck blood
      flow changes.
AB  - This study was designed to evaluate power Doppler imaging for assessment of
      urinary bladder neck blood flow in comparison with laser Doppler flowmetry (LDF)
      in an animal model. Transrectal power Doppler ultrasound (US) and LDF of the
      urinary bladder neck were performed in three anesthetized pigs during comparative
      cystometry. Normal saline (NaCl) was used for the first run, followed by a second
      run with 0.2 mol/L potassium chloride (KCl). Standardized sonographic equipment
      settings (Acuson Sequoia 512); MountainView, CA) were used for power Doppler
      imaging. Computer-assisted calculation of color pixel density (CPD) of power
      Doppler images was performed using Scion Image) software image analysis. Tissue
      perfusion units (TPU) were measured using a BLF21 laser Doppler flowmeter
      (Transonic Systems Inc., Ithaca, NY, USA). The power Doppler results were
      compared with the findings obtained by LDF. NaCl filling resulted in a mean CPD
      increase at the bladder neck from 18.65 (+/- 1.78) at empty bladder to 37.8 (+/-
      1.84) at 100 mL and to 88.32 (+/- 1.35) at full bladder capacity (C(max)) of 270
      mL, respectively. With KCl filling, a mean CPD increase from 18.65 (+/- 1.78) to
      59.63 (+/- 0.5) at 100 mL and 110.82 (+/- 2.98) at full bladder capacity (270 mL)
      was observed. The CPD increase was significantly higher for KCl than with NaCl (p
      < 0.001). With NaCl filling, bladder neck blood flow increased from 22 TPU
      (empty) to 46 TPU (100 mL) and 62.5 TPU at C(max), compared to 22 TPU, 50 TPU and
      102.5 TPU with KCl. CPD and TPU measurements showed a strong correlation at p =
      0.01. In conclusion, transrectal power Doppler US image quantification is a
      feasible and accurate method for assessing blood flow changes in the urinary
      bladder neck.

PMID- 15582239
TI  - Staging deep venous thrombosis using ultrasound elasticity imaging: animal model.
AB  - Deep venous thrombi undergo progressive hardening with age. However, the
      evolution rate remains poorly characterized by both invasive and noninvasive
      techniques. In a previous study (Emelianov et al. 2002), we demonstrated the
      potential of ultrasound elasticity imaging to noninvasively detect and age
      thrombus using a rat-based model. Knowing that thrombi harden over time is
      useful, but the value of the technique relies on whether the age of a thrombus
      can be predicted from strain estimates, and how accurate these predictions are.
      The objective of the present study is to answer these two questions. In the
      previous study, thrombus elasticity changes were monitored only on day 3, 6 and 9
      after surgically induced formation of thrombosis in rat inferior vena cavas. In
      this study, ultrasound elasticity imaging was performed on two independent groups
      of rats (16 in total) starting from day 3 through day 10 with more temporal
      samples through the thrombus maturation process. For each rat, thrombus hardness
      was quantified at each scan interval by measures of normalized strains and
      reconstructed relative Young's moduli. In both groups, strain magnitudes exhibit
      progressive decrease as clots age. The relationship between the normalized strain
      and the clot age was developed from the first group and evaluated by the second
      group. Statistical analysis showed that the age estimation accuracy is within 0.8
      day. If further research can successfully transfer the animal clot-hardening
      model to human patients, we believe that elasticity imaging will become a key
      component of venous compression ultrasound for effective diagnosis and treatment
      of deep venous thrombosis.

PMID- 15582240
TI  - Breast tissue characterization using FARMA modeling of ultrasonic RF echo.
AB  - A number of empirical and analytical studies demonstrated that the ultrasound RF
      echo reflected from tissue exhibits 1/f characteristics. In this paper, we
      propose to model 1/f characteristics of the ultrasonic RF echo by a novel
      parsimonious model, namely the fractional differencing auto regressive moving
      average (FARMA) process, and evaluated diagnostic value of model parameters for
      breast cancer malignancy differentiation. FARMA model captures the fractal and
      long term correlated nature of the backscattered speckle texture and facilitates
      robust efficient estimation of fractal parameters. In our study, in addition to
      the computer generated FARMA model parameters, we included patient age and
      radiologist's prebiopsy level of suspicion (LOS) as potential indicators of
      malignant and benign masses. We evaluated the performance of the proposed set of
      features using various classifiers and training methods using 120 in vivo breast
      images. Our study shows that the area under the receiver operating
      characteristics (ROC) curve of FARMA model parameters alone is superior to the
      area under the ROC curve of the radiologist's prebiopsy LOS. The area under the
      ROC curve of the three sets of features yields a value of 0.87, with a confidence
      interval of [0.85, 0.89], at a significance level of 0.05. Our results suggest
      that the proposed method of ultrasound RF echo model leads to parameters that can
      differentiate breast tumors with a relatively high precision. This set of RF echo
      features can be incorporated into a comprehensive computer-aided diagnostic
      system to aid physicians in breast cancer diagnosis.

PMID- 15582241
TI  - Sample volume shape for pulsed-flow velocity estimation using a linear array.
AB  - Various definitions of the sample volume (SV) shape have been proposed, but they
      are mostly based on transducers with axisymmetrical geometry. We have defined the
      SV as that spatial region in which scatterers contribute a component to the total
      gated received-signal energy above a defined threshold. This definition is
      consistent with modern pulsed transducer arrays and accounts for the need to
      impose a signal/noise threshold. Based on this definition, SVs for a typical
      linear phased-array transducer were simulated using custom-designed software. The
      effects of different transmit pulses, receive gates, apertures, SV depths and
      lateral foci were studied using a one-dimensional (1-D) beam-forming array, with
      a fixed lens in the elevation direction. Based on a simplified method of
      analysis, the features of the beam-steered SV are qualitatively similar to those
      of the nonsteered SV, when compared at the same beam-flow angle. These studies
      have helped provide a clearer understanding of the manner in which the SV energy
      distribution is affected by various parameters. The results can have potentially
      significant implications in the use of ultrasound (US) for blood velocity
      estimation, specifically with respect to locating the SV within the blood vessel
      and the origin of the velocity spectrum.

PMID- 15582242
TI  - Polyacrylamide gel containing egg white as new model for irradiation experiments
      using focused ultrasound.
AB  - A polyacrylamide (PAA) gel containing egg white as a new model for irradiation
      experiments in high-intensity focused ultrasound HIFU is introduced. The gel is
      transparent except in thermally necrosed regions which are white. The model is
      similar to, and has the same benefits as, gels containing bovine serum albumin
      (BSA) protein, but egg is less expensive than BSA. The acoustic properties of the
      gel are very favorable, similar to those of soft tissues; density 1.0 g/cm(3),
      sound speed 1540 m/s and acoustic attenuation 0.4 dB/cm at 2 MHz. We illustrate
      the usefulness of the gel in visualizing HIFU lesions and introduce a new model
      of gastric submucosal tumor in a rabbit stomach, showing that this gel can be
      formed into any desired shape. Our PAA gel containing egg white is an attractive
      candidate for a disposable acoustic material suitable for experimental
      applications of HIFU.

PMID- 15582243
TI  - EAU guidelines on urological trauma.
AB  - PURPOSE: To determine the optimal evaluation and management of genitourinary
      (renal, ureteral, bladder, urethral and genital) injuries by review of the
      world's literature on the subject. METHODS: A consensus committee convened by the
      Health Care Office of the European Association of Urology (EAU) to summarize the
      literature concerning the diagnosis and treatment of genitourinary trauma.
      RESULTS: Findings of 350 citations are reviewed. CONCLUSIONS: The genitourinary
      trauma literature still relies heavily on expert opinion and single-institution
      retrospective series. Future prospective trials of the most significant issues,
      when possible, might improve the quality of evidence that dictates practitioner
      behavior.

PMID- 15582244
TI  - Active surveillance with selective delayed intervention using PSA doubling time
      for good risk prostate cancer.
AB  - Good risk prostate cancer, defined as patients with a Gleason score of 6 or less,
      PSA<10-15, and T1c-T2a, now constitutes 50% of newly diagnosed prostate cancer.
      For most of these patients, the disease is indolent and slow growing. There is
      substantial evidence that it does not pose a threat during the lifetime of most
      patients. The challenge is to identify those patients who are not likely to
      experience significant progression while offering radical therapy to those who
      are at risk. To date, molecular markers have failed to provide sufficiently
      reliable predictive information to influence decision making. The approach to
      favorable risk prostate cancer described in this article uses estimation of PSA
      doubling time (PSA DT) to stratify patients according to the risk of progression.
      Patients who select this approach are managed initially with active surveillance.
      those who have a PSA DT of 3 years or less (based on a minimum of 3
      determinations over 6 months) are offered radical intervention. The remainder are
      closely monitored with serial PSA and periodic prostate re-biopsies (at 2, 5, and
      10 years). In this series of 299 patients, the median doubling time was 7.0
      years. 42% had a PSA DT>10 years, and 20% had a PSA DT>100 years. The majority of
      patients in this study remain on surveillance. The approach of active
      surveillance with selective delayed intervention based on PSA DT represents a
      practical compromise between radical therapy for all (which results in
      overtreatment for patients with indolent disease), and watchful waiting with
      palliative therapy only (which results in undertreatment for those with
      aggressive disease).

PMID- 15582245
TI  - Percutaneous nephrolithotomy and its legacy.
AB  - OBJECTIVE: We review the indications of Percutaneous Nephrolithotomy (PNL), its
      safety and efficacy when applied to various patient groups as well as the
      different points of technique, giving emphasis on new tips and ongoing debates.
      METHODS: A literature search was performed using MEDLINE database on PNL between
      1980 and 2004. RESULTS: Percutaneous nephrolithotomy (PNL) has been successfully
      and safely used to treat patients with renal stones for more than a quarter of a
      century. Still, the use of PNL in treating renal stones in different patient
      groups, such as children, obese patients, patients with renal congenital
      anomalies, patients who had previous open renal surgery and patients who have
      undergone renal transplantation are always of high interest. Simultaneous
      bilateral percutaneous nephrolithotomy seems to have a certain role in treating
      bilateral renal stones, especially when proficiency is achieved for unilateral
      PNL. Various aspects of the procedure such as patient positioning, renal access,
      the ideal dilating method, the type of nephrostomy tube used, as well as the
      actual need for drainage, have been debated. CONCLUSION: PNL is currently the
      procedure of choice for removal of large renal calculi. The need for well
      designed prospective randomized trials comparing PNL with alternative treatment
      modalities arises through the literature review.

PMID- 15582246
TI  - Non-invasive detection of prostate cancer by electromagnetic interaction.
AB  - OBJECTIVES: Malignant and normal tissues are known to have different
      electromagnetic properties, and various attempts have been made to use these
      information for diagnostic purposes. A nonlinear tuneable oscillator (Trimprob)
      generating extremely low energy multiple electromagnetic fields has been
      developed for non-invasive analysis of electromagnetic anisotropy in humans.
      Objective of this study was to evaluate the feasibility of prostate cancer
      detection using the TRIMprob and to evaluate its diagnostic accuracy. METHODS:
      757 men were evaluated with the TRIMprob between July 2002 and May 2003 in a
      prostate unit. The TRIMprob was moved over the surface of the patient's perineum
      while standing, normally dressed, in front of the system receiver. A single
      operator, blinded to the patient status, conducted the tests. Nonlinear resonance
      was analysed at 465, 930 and 1395 MHz. RESULTS: Analysis of resonance values at
      465 MHz showed a significant difference between controls, patients with benign
      prostatic hyperplasia and patients with prostate cancer. In our study population,
      a sensitivity of 95.5% and specificity of 42.7% for the diagnosis of prostate
      cancer with a positive and negative predictive value of 63.6% and 89.8% was
      found. CONCLUSIONS: The results of this study confirm the possibility of
      electromagnetic detection of cancer. An extracorporeal scan by the TRIMprob can
      identify patients at risk for prostate cancer, and recognise those in whom the
      risk is extremely low. The results of the present study represent a proof-of
      concept, which may open a new field of medicine.

PMID- 15582247
TI  - Are repeat biopsies required in men with PSA levels < or =4 ng/ml? A
      Multiinstitutional Prospective European Study.
AB  - OBJECTIVES: Pathological and biochemical features of prostate cancers detected on
      repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were
      evaluated and compared to those cancers detected on first biopsy. METHODS: 315
      men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound
      guided sextant biopsy and two additional transition zone biopsies (Octant
      Biopsy). All subjects whose biopsy samples were negative for prostate cancer
      underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers
      were offered surgery or radiation therapy. Pathological and clinical features of
      patients diagnosed with prostate cancer on initial and repeat biopsy were
      compared. RESULTS: Cancer detection rates on first and second biopsy were 24%
      (75/315) and 13% (29/224), respectively. Overall, of patients with clinically
      localized disease (83% of cancers detected), 87% underwent radical prostatectomy,
      11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found
      in the first biopsy group were more multifocal (p = 0.01) while cancers found on
      second biopsy were more located in the apical-dorsal region (p = 0.003). No
      significant differences were noted with respect to extracapsular extension,
      seminal vesical invasion, positive margins, final pathological stage, Gleason
      score, percentage Gleason grade 4/5, serum PSA and patient age between first and
      second biopsy. CONCLUSIONS: With an octant biopsy regime, biochemical and
      pathological features of cancers detected on initial and repeat biopsy in the PSA
      range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer
      volume suggesting identical cancer characteristics, thus advocating for a repeat
      prostate biopsy in case of a negative finding on initial biopsy.

PMID- 15582248
TI  - Is there a need for pelvic lymph node dissection in low risk prostate cancer
      patients prior to definitive local therapy?
AB  - OBJECTIVES: In men with low risk prostate cancer the need for pelvic lymph node
      dissection is controversial. Therefore, we examined how many men with favorable
      preoperative risk factors had positive lymph nodes. METHODS: 235 men with
      preoperative PSA < or =10 ng/ml, Gleason score < or =6 and positive biopsies in
      only one lobe, had radio-guided pelvic sentinel lymph node (SLN) dissection and
      radical retropubic prostatectomy (RRP) or-in case of no positive lymph nodes
      detected-a transperineal I(125) seed implantation. Eighty-four men with positive
      biopsies in both lobes and identical PSA and Gleason score had SLN dissection and
      RRP. RESULTS: In 187 men with positive biopsies in one lobe RRP was performed.
      Sixteen patients had positive lymph nodes. Median 6 SLN (mean 6.8) and 6 non
      sentinel lymph nodes (NSLN) (mean 7.3) were dissected. All men with positive
      lymph nodes also had positive SLN. Eighty-four men with positive biopsies in both
      lobes had RRP. Nine men had positive lymph nodes (10.7%). A median of 6 SLN (mean
      6.6) and 5 NSLN (mean 7.5) were dissected. All men with positive nodes had a
      single positive SLN. CONCLUSIONS: In patients with PSA < or =10 ng/ml and biopsy
      Gleason score < or =6, positive lymph nodes were identified by radio-guided
      surgery in 6.8% (positive biopsies in one lobe) and 10.7% (positive biopsies in
      both lobes). Up to 4 positive SLN were found. Therefore, we suggest not to
      dispense with an operative lymph node staging, even in low risk disease.

PMID- 15582249
TI  - 1,25 Dihydroxyvitamin D(3) receptor expression in superficial transitional cell
      carcinoma of the bladder: a possible prognostic factor?
AB  - OBJECTIVE: Vitamin D receptors (VDR) have been detected in normal tissues and in
      a number of cancer types. This study was undertaken to determine the VDR
      expression status and to elucidate the prognostic significance of VDRs in
      superficial transitional cell carcinoma (TCC) of the human bladder. METHODS: VDR
      expression was investigated in the tumour tissue blocks which were obtained by
      transurethral resection from 105 patients with superficial TCC without
      concomitant carcinoma in situ and in 30 control subjects. Median follow-up of the
      patients was 40 months. The expression of nuclear VDR was evaluated
      immunohistochemically using avidin-biotin-peroxidase method and a monoclonal VDR
      antibody. VDR staining intensity in samples were assessed semi-quantitatively and
      graded as [-] if VDR was lacking, [+] if <33% of cells were stained, [++] if 33
      66% of cells and [+++] if >66% were stained. Staining characteristics were
      compared with the clinico-pathologic results. RESULTS: VDRs were detected in
      85.7% of the patients with superficial TCC and in 66.6% of the controls (p =
      0.02). No correlation was found between VDR expression and pathological stage and
      grade (p = 0.05 and p = 0.09, respectively). Progression in pathologic stage was
      significantly higher in VDR[+++] tumours (p = 0.001). Also, disease-free survival
      was significantly lower and tumour size was significantly greater in VDR [+++]
      tumours than [-], [+] and [++] ones (p = 0.02, p = 0.008 and 0.007,
      respectively). No significant difference was found between patient age, sex,
      tumour multiplicity in terms of VDR expression. Survival was not affected by VDR
      expression. In multivariate analysis VDR expression was not found to be an
      independent prognostic factor. CONCLUSION: Superficial TCC of the bladder express
      VDRs. The association of increased VDR expression and higher disease progression
      may be useful in discriminating less differentiated superficial TCCs with poor
      outcome.

PMID- 15582250
TI  - Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients
      with bladder cancer.
AB  - OBJECTIVES: Multifocality and frequent recurrence of urothelial carcinoma of the
      urinary bladder indicate a disease of the entire "urothelial field", but little
      is known about chromosomal alterations in histologically normal urothelium.
      Histopathologically normal urothelium from patients with and without concurrent
      urothelial carcinoma was analyzed for loss of heterozygosity (LOH) on chromosomes
      8p, 9 and 17p, regions that are known to play an important role in urothelial
      carcinogenesis. MATERIALS AND METHODS: Histologically inconspicuous urothelial
      mucosa samples (n = 160) from cystectomy specimens of patients with urothelial
      carcinoma (n = 15, max. diagnosis: CIS, pT1-4; all tumors grade 3) were studied.
      Control samples (n = 50) were obtained from patients with benign prostatic
      hyperplasia (n = 30) and from cystectomies performed for invasive non-urothelial
      carcinoma (n = 20). Tissue samples were laser-microdissected and DNA was isolated
      using standard protocols. LOH analyses were performed using 16 polymorphic
      markers on chromosomes 8p, 9p/q and 17p. RESULTS: All investigated samples were
      informative for at least one microsatellite marker on each chromosome/chromosomal
      arm. Deletions were found on chromosome 9 and/or 8p in 15/160 (9.4%) of normal
      urothelial samples from urothelial cancer patients. These alterations were only
      found in 5/15 patients with urothelial carcinoma. There were no deletions on
      chromosome 17p. The marker D9S1113 on chromosome 9q33-34 was most frequently
      affected (11/15 samples, 73%). No chromosomal deletions were found in any of the
      50 urothelial control samples. CONCLUSION: Specific genetic alterations
      frequently associated with bladder cancer are detectable in histologically normal
      urothelium of patients with bladder cancer, supporting the field effect
      hypothesis in urothelial carcinogenesis. However, intramucosal spread of tumor
      cells that escape light microscopic detection remains a possibility, since normal
      urothelium and concurrent carcinomas showed matching deletions. Chromosomal
      deletions in normal bladder mucosa are not a common finding and argue against a
      frequent genomic alteration of the entire urothelial field in bladder
      carcinogenesis.

PMID- 15582251
TI  - Repeat retroperitoneal lymphadenectomy in advanced testicular cancer.
AB  - OBJECTIVES: Repeat retroperitoneal lymph node dissection (RPLND) for the
      treatment of metastatic testicular cancer is an uncommonly performed procedure.
      We evaluated the location, pathohistological results, postoperative complications
      and therapeutic outcome in 17 patients being referred for repeat RPLND after
      failure of the primary retroperitoneal approach. PATIENTS AND METHODS: 18
      patients underwent repeat RPLND after failed primary RPLND or residual tumour
      resection. We retrospectively analyzed preoperative patient characteristics,
      operative and pathohistological data from primary and repeat RPLND, morbidity and
      oncological outcome after surgery. RESULTS: All patients had nonseminomatous
      primaries with metastatic retroperitoneal lymph nodes; 4 and 14 patients had
      undergone primary RPLND and residual tumor resection (RTR), respectively, for
      metastatic testicular cancer. Prior to repeat RPLND all patients had undergone 4
      cycles of salvage chemotherapy for locoregional recurrences only with negative
      tumour markers at time of surgery. All patients demonstrated residual masses
      requiring repeat RPLND. Retroperitoneal recurrences were located at multiple
      sites: retrocaval area with infiltration of the vena cava, interaortocaval and
      paraaortic region, retrocrural space, suprahilar region, outfield metastases in
      the iliac region. Two cases required resection of the vena cava due to
      infiltration, in one case an aortic graft and an iliac graft was necessary due to
      tumour infiltration of the adventitial layer of the vessels; nephrectomy and
      resection of the sigmoid was required in another 2 patients. The most significant
      complication was chylous ascites 1 and prolonged paralytic ileus in 1 patient.
      Pathohistological examination of the resected specimen revealed viable germ cell
      tumour elements in 4 patients (22.2%), necrosis/fibrosis in 8 patients (44.4%)
      and mature teratoma in 6 patients (33.3%). At a mean follow-up of 22 (1-45)
      months, the disease specific survival rate was 89% with significant differences
      between patients with necrosis (100%), mature teratoma (85%) and viable cancer
      (50%). CONCLUSION: Recurrences after RPLND usually reflect inadequate primary
      surgery especially in the retrocaval and suprahilar region. Repeat RPLND is safe
      and effective in the majority of patients; however, it requires careful
      preoperative planning with regard to potential involvement of adjacent vascular
      and visceral structures making close interdisciplinary collaboration necessary in
      many cases. Repeat RPLND is a mandatory surgery to be performed at centres of
      expertise.

PMID- 15582252
TI  - Combination therapy with rofecoxib and finasteride in the treatment of men with
      lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).
AB  - PURPOSE: Cyclooxygenase-2 (COX-2) is expressed in human BPH tissue and displays
      either a pro-inflammatory effect or a proliferative effect on prostate cells. The
      aim of this study is to analyze whether combination therapy with rofecoxib, a COX
      2 inhibitor, and finasteride offers an advantage compared to finasteride
      monotherapy in patients with BPH. MATERIALS AND METHODS: This is a single centre
      unblinded trial. Forty-six consecutive men with LUTS and BPH were entered into
      the study and were randomized to receive rofecoxib 25mg/day plus finasteride
      5mg/day (group B) versus finasteride 5mg/day alone (group A) for 24 weeks.
      Inclusion criteria included also a prostate size greater than 40 cc. The efficacy
      and safety of treatments were assessed at baseline and at week 4, 12 and 24.
      RESULTS: In our population, both treatments (groups A and B) produced
      statistically significant improvements in total IPSS and Q(max) from baseline
      during follow-up, although they were very low in particular for the finasteride
      alone group at 4 weeks. We found that finasteride monotherapy produces very
      little improvement at the 1 month interval. In comparing group A with group B, a
      significantly higher improvement in IPSS (p=0.0001) and Q(max) (p=0.03) was
      obtained in group B at 4 weeks interval (% cases with IPSS reduction >4 points:
      group B=34.7, group A=0; % cases with Q(max) improvement >3 ml/s: group B=8.7,
      group A=0), whereas at week 24, the differences between the two treatments were
      not significant (p>0.05). CONCLUSIONS: In our population, the advantage of the
      combination therapy compared to finasteride alone is significant in a short-term
      interval (4 weeks). It can be hypothesized that the association of rofecoxib with
      finasteride induces a more rapid improvement in clinical results until the effect
      of finasteride becomes predominant.

PMID- 15582253
TI  - Prevalence and risk factors for erectile dysfunction in 2869 men using a
      validated questionnaire.
AB  - PURPOSE: To assess prevalence and risk factors for erectile dysfunction (ED) by
      using the International Index of Erectile Function- 5 (IIEF-5) in men undergoing
      a health investigation. METHODS: Men aged 20-80 years participating in a health
      screening project in the area of Vienna completed the IIEF-5 for evaluation of
      ED. In parallel, all men underwent a detailed health examination including
      physical assessment, evaluation of various life-style factors, medical history
      and a blood analysis. RESULTS: A total of 2869 men were analysed. According to
      the IIEF-5 score, 32.2% reported on any degree of ED (IIEF-5 score <22), 23.7%
      had mild ED (IIEF-5 score 17-21), 5.0% mild to moderate ED (IIEF-5 score 12-16),
      2.2% moderate ED (IIEF-5 score 8-11) and 1.3% severe ED (IIEF-5 score 5-7). The
      proportion of men with ED remained stable from 20 to 50 years (26-29%) and
      increased thereafter to 37.5% (51-60 years) and to 71.2% in those 71-80 years of
      age. Severe ED (IIEF-5 score 5-7) increased from 0.4% (20-30 years) to 0.5% (41
      50 years), 1.3% (51-60 years) and to 9.6% in those aged 71-80 years. Risk factors
      for ED were age, diabetes (OR: 3.0; 95%CI: 1.53-5.87), hyperlipidemia (OR: 2.29;
      95%CI: 1.42-3.7), lower urinary tract symptoms (OR: 2.2; 95%CI: 1.76-2.76),
      hypertension (OR: 2.05; 95%CI: 1.61-2.6), psychological stress (OR: 1.68; 95%CI:
      1.43-1.98) and low physical activity (OR: 1.35; 95%CI: 1.15-1.6) (all, p < 0.05).
      CONCLUSION: Overall, 32.2% of men in our study had ED according to the IIEF-5.
      Apart from age, most important risk factors for ED were diabetes, hyperlipidemia,
      lower urinary tract symptoms, hypertension and psychological stress.

PMID- 15582254
TI  - Chronic sildenafil improves erectile function and endothelium-dependent
      cavernosal relaxations in rats: lack of tachyphylaxis.
AB  - OBJECTIVES: Sildenafil is a widely-prescribed effective on-demand treatment of
      erectile dysfunction (ED). Chronic treatment with sildenafil could help patients
      with ED. METHODS: The effects of an 8-week long treatment with sildenafil (60
      mg/kg/d sc) in male Sprague Dawley rats were evaluated on electrically-elicited
      erectile responses in vivo before and after an acute injection of sildenafil
      (0.3mg/kg iv). In addition, endothelium-dependent and -independent relaxations of
      strips of corpus cavernosum in vitro were examined. All experiments were
      performed 36 hours after the last injection of sildenafil. RESULTS: Endothelium
      dependent relaxations of cavernosal strips to acetylcholine were enhanced after
      chronic treatment with sildenafil while relaxations to A23187 or sodium
      nitroprusside were unchanged. Frequency-dependent erectile responses elicited by
      cavernous nerve stimulation were significantly improved. Moreover, the erectile
      responses to acute sildenafil were greater in chronically-treated rats with
      sildenafil. CONCLUSIONS: This is the first report providing experimental support
      for chronic dosing with sildenafil which could be of use for patients that are
      poor responders to on-demand treatment. Chronic sildenafil may regulate the
      transduction pathway leading to the activation of eNOS but has no effect on NO
      bioavailability or on the cGMP pathway, thereby eliminating a possible concern
      for tachyphylaxis.

PMID- 15582255
TI  - Laparoscopic nephron-sparing surgery: preoperative assessment with three
      dimensional computed tomography.
AB  - OBJECTIVE: For retroperitoneal laparoscopic nephron-sparing surgery using a
      microwave tissue coagulator, it is helpful to know the relationship between the
      tumour, collecting system and vessels to prevent urinary leakage and vascular
      damage. We assessed the efficacy of multiplanar reformation and three-dimensional
      (3D) CT with the renal collecting system filled with contrast medium. METHODS:
      Fifteen patients with small renal tumours of less than 3 cm in diameter underwent
      dynamic CT examination ten minutes after injection of contrast medium of 30 ml.
      Multiplanar reformation, volume-rendered and maximum intensity projection images
      were created for determining operative approaches and for planning the operation.
      RESULTS: In all cases, the distance between the tumour and collecting system was
      measured on the multiplanar reformation. Accordingly, five cases were indicated
      for retroperitoneal laparoscopic nephron-sparing surgery using a microwave tissue
      coagulator. The remaining ten cases, due to the short distance (less than 10mm),
      were not considered good candidates for this procedure. The relationship between
      the tumour, collecting system and vessels was well shown on the volume-rendered
      and maximum intensity projection images. CONCLUSIONS: Multiplanar reformation and
      3D-CT are able to give us an understanding of the surrounding structures. They
      are helpful in defining the indications for retroperitoneal laparoscopic nephron
      sparing surgery using a microwave tissue coagulator and preoperative planning of
      nephron-sparing surgery.

PMID- 15582256
TI  - Clamping of the renal artery in laparoscopic partial nephrectomy: an old device
      for a new technique.
AB  - OBJECTIVE: We describe our experience with the transient clamping of the renal
      artery during laparoscopic partial nephrectomy for renal cancer with a double
      loop clamping device, inspired by the Rumel tourniquet. The silastic rubber loop
      is positioned around the renal artery and clinched, thus achieving arterial
      occlusion. METHODS: From November 2002 until July 2004, fourteen consecutive
      patients (mean age of 58 +/- 11.6 years) underwent laparoscopic transperitoneal
      partial nephrectomy using the silastic rubber clamping device, eight of them on
      the right side and six on the left side. Hemorrhage of the renal defect was
      controlled with bipolar electrocoagulation, argon beam coagulation, laparoscopic
      sutures, surgical and fibrin glue. RESULTS: : The mean surgical time was 198.92
      +/- 39.95 min for a mean tumour size of 2.9 +/- 2.32 cm and a mean blood loss of
      104.57 +/- 77.69 ml. The clamping device was easily and successfully positioned
      around the renal artery in 2.05 +/- 0.45 min and the mean warm ischemic time was
      25.21 +/- 6.07 min. CONCLUSIONS: The clamping device procures successful
      atraumatic occlusion of the renal artery during laparoscopic partial nephrectomy
      without the need for an additional port. As such, it could be considered as an
      alternative for the laparoscopic bulldog and Satinsky clamp.

PMID- 15582257
TI  - Sub-urethral tape treatment of female urinary incontinence--morbidity assessment
      of the trans-obturator route and a new tape (I-STOP): a multi-centre experiment
      involving 604 cases.
AB  - PURPOSE: To make an assessment of the morbidity related to using the trans
      obturator route (TOT); findings after one year for the 140 first cases and
      preliminary results of short term morbidity after 604 implants. PATIENTS AND
      METHOD: This retrospective, multi-centre study involves the 604 first procedures
      with a 1-3 month follow-up. The mean patient age was 57 years. 92% of the
      patients underwent an isolated urinary incontinence cure and 8% had associated
      surgery. 47.3% of the cases had pure stress urinary incontinence and 52.7% had
      mixed incontinence. A 12-month minimum follow-up period was applied to the first
      140 cases operated between September 2002 and January 2003. Patient assessment
      was made by a clinical examination in the first three months and their
      satisfaction rate expressed after 1 year. RESULTS: Operative complications were
      very few: 0.5% vesical perforations, 0.3% vaginal perforations, no urethral
      wounds, 0.8% 200-300 ml haemorrhages, two perineal haematomas (0.33%). The post
      operative period was marked by: 1.5% transient retentions, 2.3% transient pain,
      2.5% urinary infections, 1.3% transient dysuria. The 1-3 month follow-up of 572
      patients shows a 5.2% rate of de novo symptoms. Patient assessment of 131
      subjects after one year revealed an encouraging satisfaction rate of 85.5% with a
      1.5% rate of de novo dysuria and urgency. To date there have been no serious or
      specific complications attributable to the surgical route adopted. The morbidity
      is not affected by associated surgery. CONCLUSION: The trans-obturator route
      combines low morbidity with a low rate of de novo symptoms on a large series.
      These results will have to be corroborated by further studies.

PMID- 15582258
TI  - Perineal cellulitis following trans-obturator sub-urethral tape Uratape.
AB  - OBJECTIVE: We report two cases of perineal cellulitis due to the surgical
      treatment of female stress urinary incontinence with a trans-obturator sub
      urethral tape of Uratape (Porges). METHODS: Treatment and follow up of their
      complication were performed at the CHRU of Lille. RESULTS: In both cases, this
      complication is related to prolonged vaginal exposition of the tape. Vaginal
      erosion always occurs next to the silicon coated section of the tape. CONCLUSION:
      Such a complication has never been described yet. It shows a lack of data
      concerning human tissue tolerance of sub-urethral tapes constituents. Such
      examples should call for caution against new materials, all the more so as they
      have not yet been validated by large scale studies.

PMID- 15582259
TI  - Expression analysis and potential functional role of the CXCR4 chemokine receptor
      in bladder cancer.
AB  - OBJECTIVE: Recent analysis gave evidence for the fact that the chemokine receptor
      CXCR4 is of functional significance in the multistep procedure of metastasis
      directing tumor cells to their metastatic target organs. In our study we
      investigated the expression of the CXCR4 receptor on bladder cancer cells and the
      functional activation of the CXCR4 receptor in bladder cancer cell lines
      regarding signal transduction pathways, which are involved in metastasis.
      METHODS: Receptor transcript expression was analysed and quantified by reverse
      transcription PCR with RNA extracted from different samples of native human
      bladder cancer tissue, normal urothelium and the bladder cancer cell lines J82
      and T24. Measurement of intracellular [Ca(++)](i) and analysis of intracellular
      stress fiber formation, chemotaxis, Matrigel invasion and proliferation were
      performed in the bladder cancer cell lines J82 and T24 upon stimulation with the
      specific agonist SDF-1. RESULTS: Specific CXCR4 receptor transcripts were
      detected in normal urothelium, the bladder cancer cell lines J82 and T24 and in
      all bladder carcinoma specimens. We did not observe a quantitative correlation of
      transcript expression and tumor stage. While SDF-1 did not evoke increases in
      [Ca(++)](i) in bladder cancer cell lines, we observed a distinct rise in
      intracellular stress fiber formation, chemotactic activity, invasion through
      Matrigel coated membranes and cell growth upon stimulation with SDF-1, which was
      blocked in the presence of a specific CXCR4 receptor antibody. CONCLUSION: Our
      results support that the chemokine receptor CXCR4 is an interesting candidate for
      the future investigation of metastasis of bladder cancer in vivo.

PMID- 15582260
TI  - Identification of androgen receptors in the motoneurons of the external urethral
      sphincter in the spinal cord of female rats.
AB  - OBJECTIVES: In women, aging is associated with profound hormonal changes.
      Menopause has been implicated in the etiology of urinary tract complaints
      including incontinence, urgency and recurrent urinary tract infections. However,
      the use of hormone replacement therapy for these conditions has given conflicting
      and disappointing results. The role of androgen changes on urinary continence in
      perimenopausal women has not been studied. We studied the presence of androgen
      receptors in pudendal motoneurons controlling the external urethral sphincter of
      female rats. MATERIALS AND METHODS: A combination of retrograde labeling of
      pudendal motoneurons from the external urethral sphincter and
      immunohistochemistry for the N-terminal portion of androgen receptors on spinal
      cord sections was performed in adult female rats. RESULTS: Androgen receptors
      were identified in the nuclei of the ventral horn of the L5-L6 spinal cord.
      Pudendal motoneurons, retrogradely labeled from the external urethral sphincter,
      were identified in the dorsolateral nucleus of the ventral horn at the same
      levels. Confocal microscopy demonstrated the presence of nuclear and cytoplasmic
      androgen receptors in the cell bodies of these retrogradely labeled pudendal
      motoneurons. CONCLUSION: Our study demonstrated the presence of androgen
      receptors in the cell bodies of retrogradely labeled pudendal motoneurons
      controlling the urethral sphincter of female rats suggesting a role of androgens
      in the neuromodulation of urethral sphincter function at the spinal level.

PMID- 15582261
TI  - Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation
      driven carcinogenesis.
AB  - During chronic inflammatory processes an excess of free radicals and DNA-reactive
      aldehydes from lipid peroxidation (LPO) are produced, which deregulate cellular
      homeostasis and can drive normal cells to malignancy. Etheno (epsilon)-modified
      DNA bases are generated by reactions of DNA with a major LPO product, trans-4
      hydroxy-2-nonenal. We investigated steady state levels of epsilon-DNA adducts in
      organs, blood or urine from patients with cancer prone diseases, especially when
      related to persistent inflammatory processes. We have developed sensitive and
      specific methods for adduct detection in vivo. Hepatic etheno-adduct levels were
      significantly elevated in patients with Wilson's disease and primary
      hemochromatosis. Excess storage of copper/iron causing oxidative stress and LPO
      derived DNA-damage, are implicated in disease pathogenesis as confirmed by
      studies in LEC-rats, a model for Wilson's disease. When patients with alcohol
      related hepatitis, fatty liver, fibrosis and cirrhosis were compared with
      asymptomatic livers, excess hepatic DNA-damage was seen in all patients, except
      those with hepatitis. Etheno-deoxyadenosine excreted in urine was measured in HBV
      infected patients diagnosed with chronic hepatitis, cirrhosis and hepatocellular
      carcinoma: as compared to controls, patients had 20-90-fold increased urinary
      levels. IN CONCLUSION: epsilon-DNA adducts may serve as potential markers for
      assessing progression of inflammatory cancer-prone diseases. Also the efficacy of
      human chemopreventive interventions could be verified by using our non-invasive
      urine assay. Mechanisms and host-factors that influence the steady-state levels
      of epsilon-DNA adducts in cancer prone tissues are under investigation.

PMID- 15582262
TI  - Helicobacter pylori and gastric cancer prevention is possible.
AB  - Epidemiological data gathered during the past few years have shown an association
      between Helicobacter pylori infection and gastric carcinoma. This association is
      considered to be causal because of its biological plausibility and the existence
      of an animal model, even though the positive consequences of eradication on
      cancer prevention have not yet been definitely proven. The limited proportion of
      H. pylori infected subjects who develop a gastric cancer can be explained by host
      factors (certain alleles of IL-1beta) and bacterial factors (cag positive
      strains), and to a lesser extent by environmental factors (diet). Arguments in
      favor of the prevention of gastric carcinoma by eradicating H. pylori are now
      stronger than before, given the availability of simple and accurate diagnostic
      tests (serology) and treatment follow-up (urea breath test), as well as a 7-day
      treatment which is usually sufficient for eradication.

PMID- 15582263
TI  - Psychological stress and the risk of breast cancer: a case-control study.
AB  - OBJECTIVE: To determine whether psychological stress, in the form of past life
      events and stress at work, was associated with the development of breast cancer.
      METHODS: The study was based on a case-control study of 257 women with breast
      cancer operated during 1993-1998 in Szczecin (Poland) hospitals and 565 controls,
      free of any cancer diagnosis. The subjects were sent a detailed questionnaire
      including questions on sociodemographic data; lifestyle (lifetime recreational
      and sport activities, occupational physical activity, diet); reproductive
      history; experience of psychological stress. The subjects reported major
      stressful life events, stress of daily activity and experience of stress at work.
      Logistic regression analyses were used to estimate the odds ratios (ORs) with 95%
      confidence intervals (CIs). RESULTS: After adjustment for age and other potential
      confounders, we found that women with major life events, stress of daily
      activity, and depression had 3.7 times higher risk for breast cancer, compared to
      those which did not experience such stress (OR = 3.70; 95% CI, 2.61-5.26). Women
      who reported experience of stress at work had a nonsignificant 16% higher risk
      for breast cancer compared with those who reported no stress (OR = 1.16; 95% CI,
      0.82-1.64). A higher proportion of cases (89.1%) than controls (71.1%) reported
      that their job was stressful, very fretful or very responsible or experienced a
      major life event (OR = 4.29; 95% CI, 2.66-6.92). CONCLUSION: These findings
      suggest an association between major life events and breast cancer.

PMID- 15582264
TI  - The relationship between perceived risk, affect, and health behaviors.
AB  - In this study, we examined the relationship between affect and health behaviors.
      The study participants were women (n = 1366), aged 18-74 years, who had not been
      previously diagnosed with breast cancer, who had a working telephone number and
      address, who spoke English, who planned to be in their present residence for at
      least 1 year, and who were willing to complete the survey requirements. General
      anxiety was a significant predictor of eating a low-fat diet, in a quadratic
      manner (p < .05). General anxiety and breast cancer worry were significant
      predictors of breast self-examination, in a quadratic fashion (p < .05). None of
      four independent variables, perceived risk, cancer worry, general anxiety, and
      general depression scores, were significantly related to mammography use,
      physical activity, or fruit and vegetable consumption. We must look beyond risk
      perceptions and family history to understand motivations for health behaviors.

PMID- 15582265
TI  - Induction of P815 tumor immunity by DNA-based recombinant Semliki Forest virus or
      replicon DNA expressing the P1A gene.
AB  - AIM: To compare the prophylactic and therapeutic effects of alphaviruses in the
      same tumor model, we used a DNA-based approach to generate a replicon DNA and
      recombinant Semliki Forest virus (rSFV) particles expressing P1A, the P815
      mastocytoma tumor associated antigen, and compared the immune effect of each
      vaccine. METHODS: Six to eight-week-old female DBA/2 mice were inoculated with
      P1A plasmid or viral vaccines. Spleen cells were assayed for antigen-specific
      cytotoxic T cell activity. Tumor growth or survival rate was observed in
      preventive and therapeutic experiments, respectively. RESULTS: We found that the
      rSFV particles prevented tumor growth when delivered prior to innoculation of
      mice with P815 cells, and more importantly, improved survival when delivered
      after the initiation of tumor growth. Naked P1A replicon DNA also functioned as a
      protective and therapeutic vaccine, although with less potency than rSFV
      particles. Virus particles also elicited a stronger cellular immune response as
      measured by target cell lysis. CONCLUSION: rSFV particles have stronger specific
      prophylactic and therapeutic immune effects in mice than replicon DNA-based DNA
      vaccines, though the latter is more effective than traditional plasmid vectors
      (e.g. pCI-neo vector).

PMID- 15582266
TI  - Biomedical properties of saffron and its potential use in cancer therapy and
      chemoprevention trials.
AB  - INTRODUCTION: Chemoprevention strategies are very attractive and have earned
      serious consideration as potential means of controlling the incidence of cancer.
      An important element of anticancer drug development using plants is the
      accumulation and analysis of pertinent experimental data and purported
      ethnomedical (folkloric) uses for plants. The aim of this review is to provide an
      updated overview of experimental in vitro and in vivo investigations focused on
      the anticancer activity of saffron (Crocus sativus L.) and its principal
      ingredients. Potential use of these natural agents in cancer therapy and
      chemopreventive trials are also discussed. METHODS: A computerized search of
      published articles was performed using the MEDLINE database from 1990 to 2004.
      Search terms utilized including saffron, carotenoids, chemoprevention, and
      cancer. All articles were obtained as reprints from their original authors.
      Additional sources were identified through cross-referencing. RESULTS: Studies in
      animal models and with cultured human malignant cell lines have demonstrated
      antitumor and cancer preventive activities of saffron and its main ingredients,
      possible mechanisms for these activities are discussed. More direct evidence of
      anticancer effectiveness of saffron as chemopreventive agent may come from trials
      that use actual reduction of cancer incidence as the primary endpoint
      CONCLUSIONS: This work suggests that future research be warranted that will
      define the possible use of saffron as effective anticancer and chemopreventive
      agent in clinical trials.

PMID- 15582267
TI  - 2-Chlorodeoxyadenosine alone and in combination with cyclophosphamide and
      mitoxantrone induce apoptosis in B chronic lymphocytic leukemia cells in vivo.
AB  - The purpose of the study was to determine some apoptotic events in mononuclear
      cells obtained from peripheral blood of patients with B-cell chronic lymphocytic
      leukemia (B-CLL) during and after therapy with 2-chlorodeoxyadenosine (2-CdA; C),
      and the combination of 2-CdA with cyclophosphamide (CC), or 2-CdA with
      mitoxantrone and cyclophosphamide (CMC). Western blot technique was performed to
      estimate expression/proteolytic degradation of generally accepted apoptotic
      markers, i.e., Bcl-2 protein, lamin B, PARP-1, and caspase-3 in leukemic cells
      isolated from blood samples of patients before treatment and subjected to drug(s)
      administration. The decrease of antiapoptotic protein Bcl-2 expression and
      proteolytic cleavage of nuclear proteins--lamin B and PARP-1 were observed in
      leukemic cells of patients treated according to the above therapy protocols,
      however, each to a different level among the studied groups. The obtained results
      indicated also that procaspase-3 was cleaved and activated in leukemic cells of
      three drug(s) treated groups. However, the cleavage of procaspase-3 and the
      generation of fragments with mol. mass of 17/20 kDa occurred especially
      effectively among patients treated according to CMC regimen. The changes in
      expression/proteolytic degradation of the above selected apoptotic markers, are
      accompanied by the appearance of apoptotic morphology in leukemic cells
      originated from blood of patients treated with the above drug(s) in comparison to
      untreated ones.

PMID- 15582268
TI  - Resveratrol-induced cell growth inhibition and apoptosis is associated with
      modulation of phosphoglycerate mutase B in human prostate cancer cells: two
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass
      spectrometry evaluation.
AB  - Several studies provide evidence for the anti-carcinogenic activity of
      resveratrol, a phytoalexin present in grapes and berries, but the precise
      mechanisms involved in the modulation of prostate carcinogenesis by resveratrol
      remain to be elucidated. The inhibitory effects induced by resveratrol in human
      prostate cancer cells impact diverse cellular mechanisms associated with tumor
      initiation, promotion, and progression. In our earlier studies with prostate
      cancer cells using cDNA microarray analysis, we indicated the importance of p53
      mediated molecular targets of resveratrol. The present study based on two
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2D-SDS
      PAGE) followed by mass spectrometry analysis of human prostate cells that have
      been treated with resveratrol clearly identifies the role of phosphoglycerate
      mutase B. For the first time, we report on phosphoglycerate mutase B in the
      resveratrol-treated prostate cancer cells LNCaP, DU145, and PC-3 at the
      transcription level. Our observations raise the possibility of its effect on
      metabolic enzymes in cancer cells without affecting the normal cells.

PMID- 15582269
TI  - Simulation modeling of change to breast cancer detection age eligibility
      recommendations in Ontario, 2002-2021.
AB  - PURPOSE: The purpose of this project was to demonstrate the development and use
      of a decision support tool based on simulation modeling of breast cancer
      screening to evaluate the implications for the provision of health services and
      the economic impact of extending routine radiographic screening for breast cancer
      to women in the 40-49 age group between 2002 and 2021. METHODS: The main method
      was computer simulation with a Markov model that used published estimates of
      population size by age group, breast cancer prevalence and incidence, screening
      program participation rate, sensitivity and specificity of the screening test and
      diagnostic test, stage transition probabilities, directed diagnosis rates and
      costs. FINDINGS: The model predicted that changes to age eligibility requirements
      would result in the detection of an additional 6610 women with breast cancer in
      Ontario requiring treatment, at an additional cost of 795 Canadian per case.
      These costs include those related to screening, diagnosis and initial treatment
      and apply to the 20-year period. CONCLUSIONS: The model provided a useful
      decision support tool for those planning and implementing breast cancer screening
      programs.

PMID- 15582270
TI  - Increasing trends of cervical adenocarcinoma incidence in Central Italy despite
      Extensive Screening Programme, 1985-2000.
AB  - Incidence rates of adenocarcinoma of the uterine cervix have been reported to be
      increasing in several countries, but not in Italy. The aim of the present study
      was to analyse trends in cervical cancer incidence by histological type in two
      districts of Central Italy (Florence and Prato), covered by the Tuscany Cancer
      Registry (RTT), where cytological screening had been available since the 1970s.
      Incident cervical cancers during 1985-2000 were 1012. Estimated Annual Percent
      Change (EAPC) by age-groups and histological type were computed. Incidence
      increased for adenocarcinoma (EAPC = +5.7%; 95% confidence interval (CI)+2.8;
      +8.6); whereas, it decreased for squamous cancer (EAPC = -1.9%; 95% CI-3.8; 0)
      and for other or not specified types (EAPC = -4.4%; 95% CI-10.0; +1.5).
      Adenocarcinoma increased significantly among younger women (<55 years) but not
      among older ones, whereas squamous cell cancer decreased among older women only.
      The burden of cervical cancers might increase in the future if no specific
      preventive strategies for adenocarcinoma are implemented.

PMID- 15582271
TI  - Proceedings of the seventh international symposium on the neurobiology and
      neuroendocrinology of aging, Bregenz, Austria, July 18-23, 2004.

PMID- 15582272
TI  - Estrogen and the brain: beyond ER-alpha and ER-beta.
AB  - 17beta-Estradiol is a greatly under-appreciated neural growth and trophic factor
      for the mammalian brain of all ages. Like other growth factors, such as the
      neurotrophins, 17beta-estradiol influences neurogenesis, neuronal
      differentiation, and neuronal survival of its targets throughout life. Estrogen
      elicits developmentally regulated differentiative effects, which are not normally
      seen in the adult brain. However, re-expression of this developmental response
      occurs in the adult, following loss of trophic support, whether induced by
      estrogen deprivation or brain injury. In addition to the classical intranuclear
      estrogen receptors (ER) ER-alpha and ER-beta, we have recently identified a
      novel, plasma membrane-associated, putative ER that is neither ER-alpha nor ER
      beta, which we have designated 'ER-X'. ER-X is a developmentally regulated
      estrogen-binding protein, present in wild-type, ER-alpha gene-disrupted
      (alphaERKO) and ER-alpha null mice, which is re-expressed following ischemic
      brain injury. The preferred ligand of ER-X is 17alpha-estradiol. Although ER-X
      shares some homology with the C-terminus of ER-alpha, it is not an alternative
      splicing variant and may be a new gene. While ER-X appears to mediate 17alpha-
      and 17beta-estradiol activation of the MAPK cascade, ER-alpha, in contrast, is
      inhibitory to its activation. Estradiol activation of MAPK/ERK may be
      particularly relevant for neuroprotection during aging and Alzheimer's disease.

PMID- 15582273
TI  - Dementia-free centenarians.
AB  - BACKGROUND: A small percentage of centenarians, about 15-25%, are functionally
      cognitively intact. Among those who are not cognitively intact at 100,
      approximately 90% delayed the onset of clinically evident impairment at least
      until the average age of 92 yr. OBJECTIVE: To review current and past findings
      related to the prevalence and incidence of dementia amongst the exceptionally
      long-lived. METHODS: Findings from the various centenarian studies, world-wide,
      are reviewed. RESULTS: Neuropsychological and neuropathological correlations thus
      far suggest that there are centenarians who demonstrate no evidence of
      neurodegenerative disease. There also appear to be centenarians who despite the
      substantial presence of neuropathological markers of Alzheimer's disease did not
      meet clinical criteria for having dementia, thus suggesting the existence of
      cognitive reserve. Epigenic studies suggest a significant familial component to
      these survival advantages. CONCLUSION: Centenarians are of scientific interest as
      a human model of relative resistance to dementia.

PMID- 15582274
TI  - Association analysis between longevity in the Japanese population and polymorphic
      variants of genes involved in insulin and insulin-like growth factor 1 signaling
      pathways.
AB  - Recent studies have demonstrated a significant association between mutations in
      genes involved in the insulin/IGF1 signaling pathway and extension of the life
      span of model organisms. In this study which compared 122 Japanese
      semisupercentenarians (older than 105) with 122 healthy younger controls, we
      examined polymorphic variations of six genes which are involved in insulin/IGF1
      signaling. These genes were FOXO1A, INSR, IRS1, PIK3CB, PIK3CG, and PPARGC1A. We
      investigated the possible association of each gene locus and longevity by
      haplotype-based association analyses using 18 SNPs from public databases and the
      published literature. One INSR haplotype, which was comprised of 2 SNPs in
      linkage disequilibrium, was more frequent in semisupercentenarians than in
      younger controls.

PMID- 15582275
TI  - Poly(ADP-ribosyl)ation and aging.
AB  - Poly(ADP-ribosyl)ation is a DNA strand break-driven post-translational
      modification of proteins catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1),
      with NAD+ serving as substrate. Poly(ADP-ribosyl)ation is triggered by DNA strand
      breaks, is functionally associated with DNA repair pathways and is a survival
      factor for cells under low to moderate levels of genotoxic stress. We have
      previously described a positive correlation between poly(ADP-ribosyl)ation
      capacity of mononuclear blood cells with longevity of mammalian species. Our
      comparison of purified recombinant human and rat PARP-1 revealed that this
      correlation might be explained in part by evolutionary sequence divergence. We
      have also developed molecular genetic approaches to modulate the poly(ADP
      ribosyl)ation status in living cells. Our results revealed that PARP-1 acts as a
      negative regulator of DNA damage-induced genomic instability, the latter being
      known as an important driving force for carcinogenesis. Our recent data obtained
      in transgenic mice with selective expression of a dominant negative version of
      PARP-1 in basal skin keratinocytes indicate that PARP-1 activity suppresses skin
      papilloma formation in a two-stage skin carcinogenesis protocol. It is tempting
      to speculate that increased poly(ADP-ribosyl)ation capacity in long-lived species
      might help retard the accumulation of DNA damage and of mutations and thus slow
      down the rate of aging and of carcinogenesis more efficiently as compared with
      short-lived animals.

PMID- 15582276
TI  - Polymorphisms in androgen and estrogen receptor genes: effects on male aging.
AB  - Besides lifestyle and environmental factors, the life-long exposure to the
      endocrine milieu of gonadal steroids is a determining factor to gender specific
      features of aging. In contrast to women, men do not experience a sudden cessation
      of gonadal function comparable to menopause. However, cross-sectional and
      longitudinal population studies demonstrate that the hormones with anabolic
      actions (e.g. testosterone [T], growth hormone, insulin-like growth factor [IGF]
      1, dehydroepiandrosterone) do decrease progressively with aging in healthy men,
      and chronic systemic illnesses accelerate this process. In addition, estrogen has
      recently been established to be essential for normal physiology of the male. The
      slow progressive decline of the hypothalamic-pituitary-gonadal (HPG) function is
      thought to be responsible for many common signs and symptoms of aging men, such
      as general weakness, sexual dysfunction, and increased fat mass. There is a large
      inter-individual variation in sex hormone levels cross-sectionally within given
      age groups as well as longitudinally with aging. A contributing factor to this
      variability are the numerous functionally significant polymorphisms that have
      been detected in the receptors for androgen and estrogen. In this review, we
      summarize the recent information on some common polymorphisms in androgen and
      estrogen receptor genes and their effect on gender specific and aging-related
      symptoms and diseases of men.

PMID- 15582277
TI  - Transcriptional mechanisms of hippocampal aging.
AB  - Aging related cognitive decline is an increasing health problem but affects only
      a subset of elderly humans. This research uses outbred young (Y) and aged rats.
      Behavioral characterization distinguishes aged rats with impaired spatial
      learning (AI) and aged rats with unimpaired learning ability (AU), mimicking the
      varied susceptibility of the human population to age-associated learning
      impairment. Studies are testing a hypothesis that hippocampal transcriptional
      mechanisms and gene expression profiles linked to activator protein-1 (AP-1) and
      glucocorticoid receptor (GR), mineralocorticoid receptor (MR) or cyclic AMP
      response element binding protein (CREB) families of transcription factors
      distinguish successful or unsuccessful aging and cognition. Results from mRNA
      assays, in situ hybridization, electromobility shift assays and western
      immunoblot indicate changes in GR and CREB in AI rats. State of the art future
      approaches to define downstream transcription targets are described.

PMID- 15582278
TI  - Sex hormones and brain aging.
AB  - Sex steroids exert pleiotropic effects in the nervous system, preserving neural
      function and promoting neuronal survival. Therefore, the age-related decrease in
      sex steroids may have a negative impact on neural function. Progesterone,
      testosterone and estradiol prevent neuronal loss in the central nervous system in
      different experimental animal models of neurodegeneration. Furthermore,
      progesterone and its reduced derivatives dihydroprogesterone and
      tetrahydroprogesterone reduce aging-associated morphological abnormalities of
      myelin and aging-associated myelin fiber loss in rat peripheral nerves. However,
      the results from hormone replacement studies in humans are thus far inconclusive.
      A possible alternative to hormonal replacement therapy is to increase local
      steroidogenesis by neural tissues, which express enzymes for steroid synthesis
      and metabolism. Proteins involved in the intramitochondrial trafficking of
      cholesterol, the first step in steroidogenesis, such as the peripheral-type
      benzodiazepine receptor and the steroidogenic acute regulatory protein, are up
      regulated in the nervous system after injury. Furthermore, steroidogenic acute
      regulatory protein expression is increased in the brain of 24-month-old rats
      compared with young adult rats. This suggests that brain steroidogenesis may be
      modified in adaptation to neurodegenerative conditions and to the brain aging
      process. Furthermore, recent studies have shown that local formation of estradiol
      in the brain, by the enzyme aromatase, is neuroprotective. Therefore,
      steroidogenic acute regulatory protein, peripheral-type benzodiazepine receptor
      and aromatase are attractive pharmacological targets to promote neuroprotection
      in the aged brain.

PMID- 15582279
TI  - Low free testosterone is an independent risk factor for Alzheimer's disease.
AB  - The purpose of this study was to assess pituitary gonadotropins and free
      testosterone levels in a larger cohort of men with Alzheimer's disease (AD,
      n=112) and age-matched controls (n=98) from the Oxford Project to Investigate
      Memory and Ageing (OPTIMA). We measured gonadotropins (follicle stimulating
      hormone, FSH, and luteinizing hormone, LH), sex hormone binding globulin (SHBG,
      which determines the amount of free testosterone) and total testosterone (TT)
      using enzyme immunoassays. AD cases had significantly higher LH and FSH and lower
      free testosterone levels. LH, FSH and SHBG all increased with age, while free
      testosterone decreased. Low free testosterone was an independent predictor for
      AD. Its variance was overall explained by high SHBG, low TT, high LH, an older
      age and low body mass index (BMI). In controls, low thyroid stimulating hormone
      levels were also associated with low free testosterone. Elderly AD cases had
      raised levels of gonadotropins. This response may be an attempt to normalize low
      free testosterone levels. In non-demented participants, subclinical hyperthyroid
      disease (a risk factor for AD) which can result in higher SHBG levels, was
      associated with low free testosterone. Lowering SHBG and/or screening for
      subclinical thyroid disease may prevent cognitive decline and/or wasting in men
      at risk for AD.

PMID- 15582280
TI  - Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer's
      amyloidogenesis.
AB  - A growing body of evidence indicates that dysregulation of cerebral biometals
      (Fe, Cu, Zn) and their interactions with APP and Abeta amyloid may contribute to
      the Alzheimer's amyloid pathology, and thus metal chelation could be a rational
      therapeutic approach for interdicting AD pathogenesis. However, poor target
      specificity and consequential clinical safety of current metal-complexing agents
      have limited their widespread clinical use. To develop the next generation of
      metal chelators, we have designed and synthesized a new bifunctional molecule
      XH1, based on a novel 'pharmacophore conjugation' concept. This lipophilic
      molecule has both amyloid-binding and metal-chelating moieties covalently
      connected by amide bonds. It achieved a putative binding geometry with Abeta1-40
      peptide by the computational chemistry modeling and reduced Zn(II)-induced Abeta1
      40 aggregation in vitro as determined by turbidometry. Moreover, our pilot data
      indicated that XH1 has no significant neurotoxicity at low micromolar
      concentrations and acute animal toxicity. XH1 specifically reduced APP protein
      expression in human SH-SY5Y neuroblastoma cells and attenuated cerebral Abeta
      amyloid pathology in PS1/APP transgenic mice without inducing apparent toxicity
      and behavior disturbances. Collectively, these preliminary findings carry
      implication for XH1 being a BBB-permeable lead compound for AD therapeutics
      targeting Alzheimer's amyloidogenesis, although further studies are needed.

PMID- 15582281
TI  - Neurotropic action of androgens: principles, mechanisms and novel targets.
AB  - The importance of androgen signaling is well recognized for numerous aspects of
      central nervous system (CNS) function, ranging from sex-specific organization of
      neuroendocrine and behavioral circuits to adaptive capacity, resistance and
      repair. Nonetheless, concepts for the therapeutic use of androgens in
      neurological and mental disorders are far from being established. This review
      outlines some critical issues which interfere with decisions on the suitability
      of androgens as therapeutic agents for CNS conditions. Among these, sex-specific
      organization of neural substrates and resulting differential responsiveness to
      endogenous gonadal steroids, convergence of steroid hormone actions on common
      molecular targets, co-presence of different sex steroid receptors in target
      neuronal populations, and in situ biotransformation of natural androgens
      apparently pose the principal obstacles for the characterization of specific
      neurotropic effects of androgens. Additional important, albeit less explored
      aspects consist in insufficient knowledge about molecular targets in the CNS
      which are under exclusive or predominant androgen control. Own experimental data
      illustrate the variability of pharmacological effects of natural and synthetic
      androgens on CNS functions of adaptive relevance, such as sexual behavior,
      anxiety and endocrine responsiveness to stress. Finally, we present results from
      an analysis of the consequences of aging for the rat brain transcriptome and
      examination of the influence of androgens on differentially expressed genes with
      presumable significance in neuropathology.

PMID- 15582282
TI  - Mechanisms of the inhibitory effects of amyloid beta-protein on synaptic
      plasticity.
AB  - Alzheimer's disease can be considered a protein misfolding disease. In
      particular, inappropriate processing of a proteolytic fragment of amyloid
      precursor protein, amyloid beta-protein (Abeta), in early stages of Alzheimer's
      disease may lead to stabilization of small oligomers that are highly mobile and
      have a potential to be extremely toxic assemblies. Recently, the importance of
      such soluble species of Abeta in triggering synaptic dysfunction, long before
      neuronal loss occurs, has become apparent. Animal models have revealed that
      plasticity of hippocampal excitatory synaptic transmission is relatively
      selectively vulnerable to Abeta both in vitro and in vivo. This review focuses on
      the mechanisms of Abeta inhibition of long-term potentiation at synapses in the
      rodent hippocampus from two complimentary perspectives. Firstly, we examine
      evidence that the synaptic activity of this peptide resides primarily in
      oligomeric rather than monomeric or fibrillar Abeta species. Secondly, the
      importance of different oxidative/nitrosative stress-linked cascades including
      JNK, p38 MAPK and NADPH oxidase/iNOS-generated reactive oxygen/nitrogen free
      radicals in mediating the inhibition of LTP by Abeta is emphasised. These
      mechanistic studies provide a plausible explanation for the sensitivity of
      hippocampus-dependent memory to impairment in the early preclinical stages of
      Alzheimer's disease.

PMID- 15582283
TI  - Perspectives on reproductive senescence and biological aging: studies in
      genetically altered follitropin receptor knockout [FORKO] mice.
AB  - Increased life expectancy leads to increased age-associated health issues in both
      sexes. For menopausal women the most important of these appear to result from the
      severe estrogen deficiency caused by ovarian dysfunction. The consequences among
      others include hot flashes, osteoporosis, obesity, impaired memory, higher
      incidence of Alzheimer's disease and cardiovascular disease. Ovarian function and
      steroidogenesis are influenced by pituitary gonadotropins, including follicle
      stimulating hormone (FSH), whose actions are mediated through ovarian receptors.
      This article highlights our recent data pertinent to aging as derived from a
      novel genetically modified animal model [the FORKO mouse (FOllitropin Receptor
      KnockOut) lacking the FSH receptor. FORKO female mice experience a chronic
      depletion of estrogen (E2) from early development, and have phenotypes similar to
      aging women, with ovarian failure, obesity, skeletal changes, and ovarian tumors.
      A variety of findings support the conclusion that E2 deficiency in FORKO mice is
      responsible for their neural impairments associated with glial cell hypertrophy,
      region-specific brain cells loss, and abnormal behavior. Findings from mice with
      FSH receptor haploinsufficiency mice ('menopausal mice') are also shedding light
      on the molecular basis of menopausal conditions that include degeneration of the
      hippocampus. Many phenotypes noted in the null condition also occur in +/-
      females but in an age related manner. Thus, the FORKO mouse becomes an excellent
      model to investigate mechanisms underlying age-related changes especially when
      these events are accelerated, as in menopausal women. Opportunities abound to
      assess the potential benefits/adverse effects of hormone replacement regimen on
      various targets.

PMID- 15582284
TI  - The Japanese quail: a model for studying reproductive aging of hypothalamic
      systems.
AB  - During aging, the decline of neuroendocrine, endocrine, and behavioral components
      of reproduction ultimately leads to reproductive failure. These studies
      considered both neuroendocrine and behavioral aspects of reproductive aging in
      Japanese quail, using chronological age and reproductive status to separate
      animals into experimental groups. In Study I, age-related changes in the
      gonadotropin releasing hormone (GnRH-I) system were investigated and a sharp
      decrease was observed in GnRH-I concentration in the median eminence of aging
      animals of both sexes, whereas preoptic-lateral septal region GnRH-I
      concentrations declined only in aging males. Immunohistochemistry confirmed these
      findings since aging females retained, whereas males lost GnRH-I cells.
      Functional changes were assessed by in vitro incubation of parasaggittal
      hypothalamic slices collected from young and old inactive males and females.
      Results showed reduced baseline GnRH-I release and diminished response to
      norepinephrine (NE). Deteriorating fertility also correlated with decreased male
      sexual behavior and loss of aromatase immunoreactive (AROM-ir) neurons in the
      medial, but not lateral preoptic nucleus (POA). Sexual behavior and AROM-ir were
      restored with exogenous testosterone, which was associated with increased cell
      size in the medial POA. Comparison of cell size and number of AROM-ir cells
      showed that aged sexually active males had fewer, larger AROM-ir cells when
      compared to young males, suggesting neuroplasticity of specific neural systems
      and a critical role of estradiol in maintaining reproductive function.

PMID- 15582285
TI  - New insights into the role of neuroactive steroids in cognitive aging.
AB  - The aim of this article is to describe neuroactive steroid research that has been
      focused on their physiological role in cognitive aging, an attractive new field
      in experimental gerontology. Neuroactive steroids have been recently proposed as
      biomarkers of cognitive aging, however, their specific functions have not yet
      been fully established. For instance, data emerging from human and animal studies
      suggest a complex relationship between neuroactive steroids and/or metabolites
      and cognitive processes during aging. Thus, a better knowledge of neuroactive
      steroid brain distribution and function could broaden our understanding of their
      physiological roles and lead to novel and more effective treatments for the
      management of age-related brain disorders. To this end, newly developed
      sensitive, specific, and accurate mass spectrometry assays may allow the
      quantification of neuroactive steroids in discrete brain regions and greatly
      contribute to unravel their role in age-related cognitive deficits.

PMID- 15582286
TI  - Molecular pathophysiology and gene therapy of aging-related erectile dysfunction.
AB  - Erectile dysfunction (ED) is a major public health problem that seriously affects
      the quality of life of patients and their partners. ED is mainly associated with
      vascular disease, diabetes, smoking, and radical prostatectomy, and its
      prevalence increases significantly with aging. Vasculogenic ED, specifically
      corporal veno-occlusive dysfunction (CVOD), is caused by the impairment of the
      relaxation of the smooth muscle in the penile corpora cavernosa and occurs in 2/3
      of cases, whereas the less common neurogenic ED is due to a defective nitrergic
      neurotransmission triggered by the sexual stimulus, either at the central
      hypothalamic and spinal levels or at the penile nerves. Based on animal and cell
      studies, neurogenic ED is assumed to be caused mainly by: (a) an insufficient
      synthesis of nitric oxide (NO) due to a decrease in the levels of the penile
      neuronal nitric oxide synthase (PnNOS) or the impairment of its regulation by
      protein effectors (NMDA receptor, protein inhibitor of nNOS: PIN), occurring in
      the neuronal bodies or nerve terminals, or (b) a loss of the cells themselves by
      apoptosis caused by the induction of inducible NOS (iNOS) and the production of
      peroxynitrite. In contrast vasculogenic ED, although may involve endothelial
      damage and down-regulation of endothelial NOS (eNOS), appears to be mainly caused
      by the relative loss of smooth muscle cells and replacement by collagen fibers
      (fibrosis) that impairs tissue compliance. In this case, iNOS induction may not
      be deleterious, but a defense mechanism preventing excessive collagen deposition.
      Gene therapy to the penile corpora cavernosa of cDNAs expressing PnNOS or eNOS,
      or counteracting PIN, has been effective in ameliorating ED in the aging rat
      model that exhibits both neurogenic ED and CVOD. cDNA constructs for other genes
      involved in the control of penile erection have also been successfully tested.
      Gene transfer into the penis may soon translate to the clinic as a therapy aimed
      to cure the underlying conditions in ED, including fibrosis, as opposed to the
      facilitation of erection on demand offered by the current oral therapies.

PMID- 15582287
TI  - Differential regulation of apoptotic cell death in senescent human cells.
AB  - Aging of human cells can be reproduced in monolayer cultures, revealing the
      phenotype of replicative senescence. It was shown that diploid human fibroblasts
      enter a stable growth arrest phenotype at the end of their lifespan and, in
      particular, these cells are resistant to various apoptotic stimuli. In contrast,
      human endothelial cells from the umbilical vein (HUVEC) acquire a proapoptotic
      phenotype when reaching senescence and this probably results from reactive oxygen
      species (ROS) induced damage and associated signaling. Ceramides were shown to
      accumulate in senescent fibroblasts and are also known as potent regulators of
      apoptotic cell death. To further study age-associated changes in proneness to
      apoptosis between fibroblasts and endothelial cells, both cell types were
      challenged by administration of exogenous ceramide and apoptotic cell death was
      determined. While ceramide can efficiently induce apoptosis in both young and
      senescent cells of either histotype, quantitative evaluation of the data show
      that senescent fibroblasts are more resistant to apoptosis induction when
      compared to their young counterparts, whereas in the case of endothelial cells
      proneness for apoptosis is increased in senescent cells. Together, these data
      suggest significant differences in the regulation of apoptosis associated with
      senescence in fibroblasts and endothelial cells.

PMID- 15582288
TI  - Melatonin, human aging, and age-related diseases.
AB  - The worldwide prolongation of the mean life expectancy has resulted in a rapid
      increase of the size of the elderly population (over the age of 60), both in
      numbers and as a proportion of the whole. As a consequence, increasing the number
      of potential beneficiaries of health and pension funds, mainly those aged 65 and
      over raises many social and economic problems since they are supported by a
      relatively smaller number of potential contributors, i.e. those in the
      economically active ages between 18 and 64. Therefore, there is a search for any
      therapeutic agent improving quality of life in the elderly. A role for melatonin
      as such a compound was recently suggested. In this survey, data on the possible
      role of melatonin in human aging and age-related diseases are briefly presented.
      Undoubtedly the aging process is multi-factorial, and no single factor has been
      identified which satisfactorily explains the phenomenon. Although many theories
      relating the pineal gland and its secretory product melatonin to aging have been
      proposed, the role of this agent in the aging process is still unclear. However,
      for several reasons it seems reasonable to postulate a role for melatonin in this
      process. Melatonin levels decline gradually over the life-span and may be related
      to lowered sleep efficacy, very often associated with advancing age, as well as
      to deterioration of many circadian rhythms. Melatonin exhibits immunomodulatory
      properties, and a remodeling of immune system function is an integral part of
      aging. Finally, because melatonin is a potent free radical scavenger, its
      deficiency may result in reduced antioxidant protection in the elderly which may
      have significance not only for aging per se but also may contribute to the
      incidence or severity of some age-related diseases. Presently available data do
      not allow us to conclude that melatonin may have a role in extending normal
      longevity. However, although melatonin cannot be recognized as 'rejuvenating'
      agent, some of its actions may be beneficial for the aging process.
      Administration of melatonin may improve temporal organization in advanced age.
      Moreover, it has beneficial effects on sleep as well as age-related diseases.
      Although recommendations of melatonin supplementation in elderly should be
      considered, there is a need for extensive studies on the use of melatonin in
      order to improve the quality of life in advanced age.

PMID- 15582289
TI  - Drug therapy in the elderly.
AB  - Drug dosage in the elderly requires an understanding of the age-dependent changes
      in drug disposition and sensitivity. The most important pharmacokinetic
      alteration is a decline in renal function, the elderly should therefore be
      treated as renally insufficient patients. Metabolic clearance is primarily
      reduced with drugs that display high hepatic extraction, whereas the metabolism
      of drugs with low hepatic extraction usually is not diminished. The reduction of
      metabolic clearance is especially pronounced in malnourished or frail patients.
      The water content of the aging body decreases, the fat content rises. Hence the
      distribution volume of hydrophilic drugs may be reduced in the elderly, resulting
      in increased plasma concentrations. In contrast, the distribution volume of
      liphophilic drugs is increased, their plasma concentrations may decrease.
      Intestinal absorption of most drugs is not altered in the elderly. Aside of these
      pharmacokinetic changes, one of the characteristics of old age is a progressive
      decline in counterregulatory (homeostatic) mechanisms. Therefore, drug effects
      are attenuated less, the responses are usually stronger than in younger subjects,
      the rate and intensity of adverse effects are higher. Examples of drug actions
      augmented is this manner are postural hypotension with agents that lower blood
      pressure, dehydration and electrolyte disturbances in response to diuretics,
      bleeding complications with oral anticoagulants, hypoglycemia with antidiabetics,
      and gastrointestinal irritation with non-steroidal anti-inflammatory drugs. The
      brain is an especially sensitive drug target in old age. Psychotropic drugs,
      anticonvulsants, and centrally acting antihypertensives may impede intellectual
      function and motor coordination. Hence drugs should be used restrictively in
      geriatric patients.

PMID- 15582290
TI  - Age impairments in sleep, metabolic and immune functions.
AB  - Age-related sleep impairments are chronic and common, occurring even in the
      absence of diagnosable disorders. Additional loss of sleep occurs with clinical
      sleep disorders, many of which can be ameliorated. This literature, reviewed
      below, raises the question of the possible biological consequences of age
      related, chronic sleep loss, an area that is poorly understood at present. Some
      of the more age-relevant theories about sleep loss will be explored in a review
      of current research on sleep deprivation arising from normal aging, experimental
      induction and pathology. The biological consequences of sleep deprivation in
      young adults include metabolic, systemic inflammatory and immune changes that are
      similar to those of aging and age-related disorders. The possibility that chronic
      sleep impairment contributes to age changes in metabolism, systemic inflammation
      and immunocompetence is explored.

PMID- 15582291
TI  - The neuroendocrine regulation of Drosophila aging.
AB  - The rate of aging is regulated by hormones in insects and, most likely, in
      mammals. Mutations of the insulin-signaling pathway extend lifespan in the fruit
      fly and influence the level of other hormones, specifically juvenile hormone and
      the sterol ecdysone, each of which may directly influence senescence. With new
      genetic and genomic tools in Drosophila biology we are now exploring how the
      neuroendocrine system responds to environmental conditions to modify insulin
      action, how these signals control secondary hormones, and how these messages
      together modulate animal aging.

PMID- 15582292
TI  - Ink4a/Arf links senescence and aging.
AB  - The mammalian INK4a/ARF locus encodes two linked tumor suppressor proteins,
      p16INK4a and ARF, which respectively regulate the retinoblastoma (RB) and p53
      pathways. Genetic data have firmly established that both proteins possess
      significant in vivo tumor suppressor activity. In addition to their non
      overlapping roles in preventing cancer, one or both proteins are induced under
      certain circumstances in most cultured murine and human cell types, and thereby
      are critical effectors of senescence. Likewise, data from murine models have
      suggested that this anti-cancer growth inhibitory activity of the locus can
      similarly affect permanent growth arrest in vivo. When such in vivo senescence
      occurs in a cell possessing self-renewal potential (e.g. a tissue stem cell),
      there is an attendant decline in the regenerative capabilities of the organ
      maintained by that stem cell. In turn, the concomitant decline of this stem cell
      reserve is a cardinal feature of mammalian aging. Expression of the INK4a/ARF
      locus, therefore, appears not only to be a major suppressor of cancer, but also
      an effector of mammalian aging.

PMID- 15582294
TI  - The inoculum effect: fact or artifact?

PMID- 15582293
TI  - IGF-1 signaling and aging.
AB  - We briefly compare calorie restriction, GHRH-R and Pit-1 mutants with knockout
      phenotypes of GH receptor, IGF-1 receptor and p66Shc, to make some general
      conclusions. Growth, fertility and longevity phenotypes may dissociate in some of
      these mutants, and we try to interpret this. Follows a short discussion on the
      importance of genetic background for aging studies in mice. We then evoke studies
      in C. elegans showing that lifespan may be regulated in a non-cell-autonomous
      fashion, and that the nervous system could play a central role therein. Recent
      findings on DILP-2 regulation in Drosophila transpose this hypothesis of
      endocrine lifespan regulation to insects. Work in mice shows that inactivation of
      the insulin receptor specifically in the adipose tissue is sufficient to increase
      the mouse lifespan. In summary, exciting findings obtained in very different
      model organisms are rapidly converging and suggest that animal lifespan may be
      subject to endocrine regulation. Interestingly, the hypothalamus centralizes many
      age related hormonal regulations and at the same time participates in the
      integration of numerous nutritional signals, such that one could ask whether the
      hypothalamus may be at the crossroads of metabolic and endocrine lifespan
      regulation.

PMID- 15582295
TI  - Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a
      high-molecular-weight constituent of cranberry.
AB  - The sensitivity of a large number of antibiotic-resistant and nonresistant
      Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass,
      nondialysable constituent of cranberry juice was tested. Confluent monolayers of
      gastric cell line in microtiter plate wells were exposed to bacterial suspensions
      prepared from 83 H. pylori isolates from antibiotic-treated and untreated
      patients in the presence and absence of the cranberry constituent. Urease assay
      was used to calculate the percentage of adhesion inhibition. In two thirds of the
      isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the
      nondialysable material. There was no relationship between the antiadhesion effect
      of the cranberry material and metronidazole resistance in isolates from either
      treated or untreated patients (N=35). Only 13 isolates (16%) were resistant to
      both the nondialysable material and metronidazole, and 30 (36%) were resistant to
      the nondialysable material alone. There was no cross-resistance to the
      nondialysable material and metronidazole. These data suggest that a combination
      of antibiotics and a cranberry preparation may improve H. pylori eradication.

PMID- 15582296
TI  - In vitro alterations of intestinal bacterial microbiota in fecal samples during
      storage.
AB  - The human gastrointestinal tract harbors an extremely diverse and complex
      microbial ecosystem. Most of the existent data about the enteric microflora have
      been generated using stool samples, but the collection and storage of fecal
      samples are often problematic. The influence of the storage of stool samples on
      the bacterial diversity and the degradation of bacterial DNA was analysed in this
      study. Stool samples from 5 healthy volunteers were exposed to different storage
      temperatures and durations. The bacterial diversity and the amount of intact
      bacterial DNA were analysed by single-stranded conformation polymorphism analysis
      (SSCP) and real-time polymerase chain reaction (PCR), both using a 16S rDNA
      approach. Additionally, biopsy specimens were taken from 3 of the 5 individuals
      to compare fecal and mucosal flora. The bacterial diversity of the fecal flora
      and the total number of bacteria were significantly reduced after 8 and 24 hours
      at both room temperature and 4 degrees C. The mucosa-associated bacterial
      microflora showed substantial differences compared with the fecal flora. The
      observed alterations of fecal flora during storage point to the difficulty of the
      molecular analysis of the bacterial diversity and the enumeration of bacterial
      cells in fecal samples.

PMID- 15582297
TI  - Interaction of granulocyte colony-stimulating factor and high doses of liposomal
      amphotericin B in the treatment of systemic murine scedosporiosis.
AB  - Because human infections by Scedosporium prolificans are difficult to treat and
      show a very poor outcome, new therapeutic strategies are needed. Liposomal
      amphotericin B (LAMB) (40 mg/kg/day) increased significantly the mean survival
      time in immunosuppressed mice compared with a control group (22.6 vs. 8.8 days).
      Amphotericin B deoxycholate (1.5 mg/kg/day) and granulocyte colony-stimulating
      factor (G-CSF) (300 microg/kg/day) were ineffective. The combination of LAMB (40
      mg/kg/day) and G-CSF (150 or 300 microg/kg/day) did not improve the results
      obtained with LAMB alone.

PMID- 15582298
TI  - Improved diagnosis of pulmonary tuberculosis by detection of free and immune
      complex-bound anti-30 kDa antibodies.
AB  - The 30 kDa secreted antigen of Mycobacterium tuberculosis was purified to
      homogeneity by serial chromatography, and enzyme linked immunosorbent assay
      (ELISA) was used to evaluate its diagnostic value in patients with pulmonary
      tuberculosis. The immunoglobulin (Ig) antibodies G, A, and M were estimated in
      the two groups: patients who were smear- and culture-positive (S+C+) for
      pulmonary tuberculosis and normal healthy subjects (NHS). Sensitivity of 67.4%,
      14.8%, and 14.3%, with the specificity of 99%, 96.7%, and 92% were obtained for
      the 3 isotypes respectively. Combination of the results of IgG and IgA increased
      the sensitivity to 71%, with 97% specificity. Polyethylene glycol precipitation
      of the circulating immune complexes (CIC) in sera was carried out. The CIC bound
      antibodies offered a sensitivity of 92.5%, 85.4%, and 68.7%, respectively for the
      S+C+, S-C+, and S-C- patients, while the specificity was 96.6%. Thus CIC-bound
      antibodies promise to be a better diagnostic tool in the detection of
      tuberculosis.

PMID- 15582299
TI  - Release of daptomycin from polymethylmethacrylate beads in a continuous flow
      chamber.
AB  - Because daptomycin is active against Gram-positive cocci, it may be useful in the
      treatment and prevention of bone and joint infections when incorporated into
      polymethylmethacrylate (PMMA). The release kinetics of daptomycin from PMMA were
      studied in a continuous flow chamber designed to simulate in vivo conditions.
      Three-millimeter beads containing 2.5%, 7.5%, and 15.0% daptomycin (weight
      daptomycin per weight PMMA) were individually placed in a chamber with 1 mL Krebs
      Ringer buffer flowing at 1 mL/hour. The majority of daptomycin was released in
      the first 24 hours. The mean peak concentrations were 13.4, 62.3, and 146.7
      microg/mL; the mean AUC0-infinity were 30, 272, and 1204 h x microg/mL; and the
      mean percentages of daptomycin released were 6%, 18%, and 42% for the beads
      containing 2.5%, 7.5%, and 15.0% daptomycin, respectively. Daptomycin is released
      from PMMA in a continuous flow chamber at a rate similar to that previously
      determined by our laboratory for vancomycin.

PMID- 15582300
TI  - In vitro activities of tigecycline against clinical isolates from Shanghai,
      China.
AB  - To evaluate the in vitro activity of tigecycline, the minimum inhibitory
      concentrations (MICs) of tigecycline against 1,201 strains of recent clinical
      isolates from 10 hospitals in Shanghai, China were determined and compared with
      selected comparators. Results showed that tigecycline had broad-spectrum
      antimicrobial activity. It was highly active against Gram-positive cocci,
      including methicillin-resistant Staphylococcus spp., penicillin-intermediate
      Streptococcus pneumoniae, Enterococcus faecalis and E. faecium. Tigecycline also
      had good activity against most strains of Enterobacteriaceae, Haemophilus
      influenzae, Neisseria gonorrhoeae, and Moraxella catarrhalis. However, it was
      poorly active against Acinetobacter baumannii and Pseudomonas aeruginosa.
      Tigecycline was highly active against anaerobic Gram-positive cocci such as
      Peptococcus spp. The in vitro activity of tigecycline was significantly better
      than that of minocycline and tetracycline. It was as active as or slightly more
      active than vancomycin and teicoplanin in the activity against resistant aerobic
      Gram-positive cocci. Tigecycline was bactericidal against all Gram-positive cocci
      tested except Enterococcus spp. Inoculum size but not pH of medium or
      concentration of human serum in broth had significant effect on the in vitro
      activity of tigecycline. Aged media (48-72 hours after preparation) used in the
      test and specific resistance problem in China may have some effects on MIC values
      of tigecycline.

PMID- 15582301
TI  - Epidural abscess and osteomyelitis due to Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans is a microaerophilic, fastidious Gram
      negative rod that most commonly causes periodontitis and odontogenic infections.
      We report the first case of an epidural abscess and osteomyelitis due to this
      organism resulting from self-extraction of carious teeth. The patient responded
      to surgical debridement and prolonged antimicrobial therapy with intravenous
      ceftriaxone.

PMID- 15582302
TI  - Vibrio cholerae (non-O1, non-O139) sepsis in a child with Fanconi anemia.
AB  - A 9-year-old female child who was a known case of Fanconi anemia was admitted to
      hospital because of fever and gastrointestinal symptoms. Blood culture at the
      time of admission yielded growth of Gram-negative curved rod that was identified
      as Vibrio cholerae (non-O1, non-O139), whereas repeated fecal cultures were
      negative for enteropathogens. To our knowledge, this is the first case of V.
      cholerae (non-O1, non-O139) septicemia associated with Fanconi anemia.

PMID- 15582303
TI  - Susceptibility of meropenem and comparators tested against 30,634
      Enterobacteriaceae isolated in the MYSTIC Programme (1997-2003).
AB  - A total of 30,634 global Enterobacteriaceae isolates collected from the MYSTIC
      (Meropenem Yearly Surveillance Test Information Collection) Programme were tested
      using a reference methodology against meropenem and seven other broad-spectrum
      agents commonly used in the hospital setting (1997-2003). The most active
      compound was meropenem (99.6% susceptible), followed by imipenem (98.4%),
      cefepime (94.0%), gentamicin (86.8%), piperacillin/tazobactam (85.8%),
      ceftazidime (85.0%), ciprofloxacin (84.6%), and tobramycin (84.5%). Continued
      surveillance of antimicrobial compounds' in vitro activity is necessary to
      recommend regimens that are likely to be effective in clinical practice.

PMID- 15582304
TI  - MIC quality control guidelines for doxycycline when testing gram-positive control
      strains by the reference methods.
AB  - With emerging resistance to fluoroquinolones, there arises a need to establish
      quality control (QC) guidelines for doxycycline, an effective alternative for
      treating various community-acquired respiratory tract infections. This
      multicenter study was performed to establish QC guidelines for susceptibility
      testing those Gram-positive QC organisms against doxycycline. The proposed three
      or four log2 dilution MIC ranges included 100.0% of the doxycycline MIC values
      reported.

PMID- 15582305
TI  - The year in atherothrombosis.

PMID- 15582306
TI  - Meeting highlights of the 15th annual Scientific Sessions of the American Society
      of Echocardiography: June 26 to 30, 2004.
AB  - "Echocardiography is the heart of clinical cardiology" was an appropriate theme
      for the 15th Scientific Sessions of the American Society of Echocardiography.
      Care of the cardiovascular patient is constantly changing, and this meeting
      showcased how echocardiographic and Doppler methods continue to be critically
      important to detect and quantify disease, determine response to therapy, and
      guide clinical decision making in contemporary medicine. This highly successful
      five-day educational event attracted a record number of attendees and focused on
      disease-based clinical applications of the latest technological advances in
      cardiac ultrasound, including advances in diagnosis and treatment of heart
      failure, valvular disease, coronary disease, and congenital disease.

PMID- 15582307
TI  - Drug-induced atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained rhythm disorder observed in
      clinical practice and predominantly associated with cardiovascular disorders such
      as coronary heart disease and hypertension. However, several classes of drugs may
      induce AF in patients without apparent heart disease or may precipitate the onset
      of AF in patients with preexisting heart disease. We reviewed the literature on
      drug-induced AF, using the PubMed/Medline and Micromedex databases and lateral
      references. Successively, we discuss the potential role in the onset of AF of
      cardiovascular drugs, respiratory system drugs, cytostatics, central nervous
      system drugs, genitourinary system drugs, and some miscellaneous agents. Drug
      induced AF may play a role in only a minority of the patients presenting with AF.
      Nevertheless, it is important to recognize drugs or other agents as a potential
      cause, especially in the elderly, because increasing age is associated with
      multiple drug use and a high incidence of AF. This may contribute to timely
      diagnosis and management of drug-induced AF.

PMID- 15582308
TI  - Proposal for contemporary screening strategies in families with hypertrophic
      cardiomyopathy.
AB  - Screening families with hypertrophic cardiomyopathy (HCM) presents a common
      clinical problem to practicing cardiologists, internists, and pediatricians. The
      traditional recommended strategy for screening relatives in most HCM families
      calls for such evaluations with echocardiography (and electrocardiogram [ECG]) on
      a 12- to 18-month basis, usually beginning at about age 12 years. If such tests
      show no evidence of left ventricular hypertrophy, i.e., without one or more
      segments of abnormally increased wall thickness by the time full growth and
      maturation is achieved (at the age of about 18 to 21 years), it has been
      customary practice to conclude that HCM is probably absent and reassure family
      members accordingly that further echocardiographic testing is unnecessary.
      However, novel developments in the definition of the genetic causes of HCM have
      defined both substantial molecular diversity and heterogeneity of the disease
      expression including (in some relatives) incomplete phenotypic penetrance and
      delayed, late-onset left ventricular hypertrophy well into adulthood. These
      observations have unavoidably reshaped the customary practice of genetic
      counseling and established a new proposed paradigm for clinical family screening
      of HCM families. Therefore, in the absence of genetic testing, strong
      consideration should be given to extending diagnostic serial echocardiography
      past adolescence and into mid-life for those family members with a normal
      echocardiogram and ECG. Of note, recent developments in laboratory DNA-based
      diagnosis for HCM could potentially avoid the necessity for serial
      echocardiography in many such relatives.

PMID- 15582309
TI  - Influence of treatment duration with a 600-mg dose of clopidogrel before
      percutaneous coronary revascularization.
AB  - OBJECTIVES: We examined clinical outcomes in the Intracoronary Stenting and
      Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT)
      trial based on the duration of pretreatment with a 600-mg loading dose of
      clopidogrel. BACKGROUND: The influence of the treatment duration with a 600-mg
      dose of clopidogrel before percutaneous coronary revascularization on early
      outcomes remains uncertain. METHODS: Among 2,159 patients with coronary disease
      who underwent percutaneous coronary intervention (PCI) in the ISAR-REACT trial,
      we examined clinical outcomes relative to the duration of pretreatment with a 600
      mg dose of clopidogrel: (2 to 3 h, 3 to 6 h, 6 to 12 h, or >12 h). Patients were
      randomly assigned to adjunctive therapy with abciximab or placebo at the
      beginning of the study. The primary end point was a composite of death,
      myocardial infarction, or urgent revascularization within 30 days after
      randomization. RESULTS: No significant differences were observed between patient
      groups regarding the duration of pretreatment, irrespective of assignment to
      abciximab or placebo (p = 0.27 for interaction among abciximab/clopidogrel and
      placebo/clopidogrel treatment at each time interval). Occurrence of major
      bleeding also did not differ according to time of initial clopidogrel dosing.
      CONCLUSIONS: For low-to-intermediate risk patients treated with a 600-mg loading
      dose of clopidogrel before PCI, incremental clinical benefit within the first 30
      days from durations of pretreatment >2 to 3 h was not evident.

PMID- 15582310
TI  - Noninvasive identification of patients with early coronary atherosclerosis by
      assessment of digital reactive hyperemia.
AB  - OBJECTIVES: We investigated the value of reactive hyperemia peripheral arterial
      tonometry (RH-PAT) as a noninvasive tool to identify individuals with coronary
      microvascular endothelial dysfunction. BACKGROUND: Coronary endothelial
      dysfunction, a systemic disorder, represents an early stage of atherosclerosis;
      RH-PAT is a technique to assess peripheral microvascular endothelial function.
      METHODS: Using RH-PAT, digital pulse volume changes during reactive hyperemia
      were assessed in 94 patients without obstructive coronary artery disease and
      either normal (n = 39) or abnormal (n = 55) coronary microvascular endothelial
      function; RH-PAT index, a measure of reactive hyperemia, was calculated as the
      ratio of the digital pulse volume during reactive hyperemia divided by that at
      baseline. RESULTS: Average RH-PAT index was lower in patients with coronary
      endothelial dysfunction compared with those with normal coronary endothelial
      function (1.27 +/- 0.05 vs. 1.78 +/- 0.08: p < 0.001). An RH-PAT index <1.35 was
      found to have a sensitivity of 80% and a specificity of 85% to identify patients
      with coronary endothelial dysfunction. CONCLUSIONS: Digital hyperemic response,
      as measured by RH-PAT, is attenuated in patients with coronary microvascular
      endothelial dysfunction, suggesting a role for RH-PAT as a noninvasive test to
      identify patients with this disorder.

PMID- 15582311
TI  - Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor
      of increased risk for cardiac events independent of albuminuria.
AB  - OBJECTIVES: This study aimed to investigate the prevalence of a reduced
      glomerular filtration rate (GFR) with and without albuminuria and its ability to
      predict cardiac events in asymptomatic diabetic patients undergoing stress-rest
      thallium-201 myocardial perfusion single-photon emission computed tomography.
      BACKGROUND: Diabetic patients have a higher prevalence of asymptomatic coronary
      heart disease. Therefore, identifying predictors of cardiac events in
      asymptomatic diabetic patients is needed. METHODS: In 269 asymptomatic patients,
      baseline evaluation included diabetes-related complications, including creatinine
      clearance (CrCl) and albuminuria. During follow-up (mean 2.3 +/- 1.0 years), all
      cardiac events were recorded. RESULTS: Seventy-seven patients (29%) had a reduced
      GFR defined by CrCl <60 ml/min/1.73 m(2). Compared with the 177 patients with
      CrCl >/=60 ml/min/1.73 m(2), the reduced GFR group was older (p < 0.0001), had a
      longer duration of diabetes (p = 0.002), and had a higher prevalence of
      albuminuria (p = 0.04). Nevertheless, 35% of the reduced GFR group had
      normoalbuminuria. Patients with reduced GFR had a significant two-fold increase
      in total cardiac events (unstable angina, nonfatal myocardial infarction, and
      cardiac procedures) (25% vs. 13%, p = 0.019), and multivariate analysis found
      that reduced GFR was an independent predictor of cardiac events (odds ratio [OR]
      2.2, 95% confidence interval [CI] 1.1 to 4.46). Other independent predictors of
      cardiac events included stress-induced abnormal myocardial perfusion imaging (OR
      3.1, 95% CI 1.3 to 7.5), an electrocardiographic ischemic response (OR 2.7, 95%
      CI 1.01 to 7.14), and peripheral artery disease (OR 2.1, 95% CI 1.05 to 4.23);
      however, albuminuria was not. CONCLUSIONS: A reduced GFR was common in our group
      of asymptomatic diabetic patients and was associated with a two-fold increase in
      cardiac events. Multivariate analysis found that reduced GFR independent of
      albuminuria was a significant predictor of cardiac events.

PMID- 15582312
TI  - Long-term patency of saphenous vein and left internal mammary artery grafts after
      coronary artery bypass surgery: results from a Department of Veterans Affairs
      Cooperative Study.
AB  - OBJECTIVES: This study defined long-term patency of saphenous vein grafts (SVG)
      and internal mammary artery (IMA) grafts. BACKGROUND: This VA Cooperative Studies
      Trial defined 10-year SVG patency in 1,074 patients and left IMA patency in 457
      patients undergoing coronary artery bypass grafting (CABG). METHODS: Patients
      underwent cardiac catheterizations at 1 week and 1, 3, 6, and 10 years after
      CABG. RESULTS: Patency at 10 years was 61% for SVGs compared with 85% for IMA
      grafts (p < 0.001). If a SVG or IMA graft was patent at 1 week, that graft had a
      68% and 88% chance, respectively, of being patent at 10 years. The SVG patency to
      the left anterior descending artery (LAD) (69%) was better (p < 0.001) than to
      the right coronary artery (56%), or circumflex (58%). Recipient vessel size was a
      significant predictor of graft patency, in vessels >2.0 mm in diameter SVG
      patency was 88% versus 55% in vessels </=2.0 mm (p < 0.001). Other positive
      significant predictors of graft patency were use of aspirin after bypass, older
      age, lower serum cholesterol, and lowest Canadian Functional Class (p < 0.001 to
      0.058). CONCLUSIONS: The 10-year patency of IMA grafts is better than SVGs. The
      10-year patency for SVGs is better and the 10-year patency for IMA grafts is
      worse than expected. The 10-year patency of SVGs to the LAD is better than that
      to the right or circumflex. The best long-term predictors of SVG graft patency
      are grafting into the LAD and grafting into a vessel that is >2.0 mm in diameter.

PMID- 15582313
TI  - Echocardiographic parameters of ventricular dyssynchrony validation in patients
      with heart failure using sequential biventricular pacing.
AB  - OBJECTIVES: We sought to evaluate the relationship between hemodynamic and
      ventricular dyssynchrony parameters in patients undergoing simultaneous and
      sequential biventricular pacing (BVP). BACKGROUND: Various echocardiographic
      parameters of ventricular dyssynchrony have been proposed to screen and optimize
      BVP therapy. METHODS: Forty-one patients with heart failure undergoing BVP
      implantation were studied. Echocardiography coupled with tissue tracking and
      pulsed Doppler tissue imaging (DTI) was performed before and after BVP
      implantation and after three months of optimized BVP. Indexes of inter- or
      intraventricular dyssynchrony were correlated with hemodynamic changes during
      simultaneous and sequential BVP (10 intervals of right ventricular [RV] or left
      ventricular [LV] pre-excitation). RESULTS: Variations in intra-LV delay(peak),
      intra-LV delay(onset), and index of LV dyssynchrony measured by pulsed DTI were
      highly correlated with those of cardiac output (r = -0.67, r = -0.64, and r = 
      0.67, respectively; p < 0.001) and mitral regurgitation (r = 0.68, r = 0.63, and
      r = 0.68, respectively; p < 0.001), whereas variations in the extent of
      myocardium displaying delayed longitudinal contraction (r = -0.48 and r = 0.51,
      respectively; p < 0.05) and the variations in septal-to-posterior wall motion
      delay (r = -0.41, p < 0.05 and r = 0.24, p = NS, respectively) were less
      correlated. The changes in interventricular dyssynchrony were not significantly
      correlated (p = NS). Compared with simultaneous BVP, individually optimized
      sequential BVP significantly increased cardiac output (p < 0.01), decreased
      mitral regurgitation (p < 0.05), and improved all parameters of intra-LV
      dyssynchrony (p < 0.01). At three months, a significant reverse mechanical LV
      remodeling was observed with significantly decreased LV volumes (p < 0.01)
      associated with an increased LV ejection fraction (p = 0.035). CONCLUSIONS:
      Specific echocardiographic measurements of ventricular dyssynchrony are highly
      correlated with hemodynamic changes and may be a useful adjunct in the selection
      and optimization of BVP. Individually optimized sequential BVP provided a
      significant early hemodynamic improvement compared with simultaneous BVP.

PMID- 15582314
TI  - Prophylactic implantable cardioverter-defibrillator therapy in patients with left
      ventricular systolic dysfunction: a pooled analysis of 10 primary prevention
      trials.
AB  - Strategies to decrease sudden cardiac death in patients with left ventricular
      systolic dysfunction are evolving. Recent clinical trials have evaluated the role
      of prophylactic implantable cardioverter-defibrillators (ICDs) in patients with
      and without additional risk stratifiers. We pooled studies comparing treatment
      with and without ICDs from published data and presented abstracts, irrespective
      of QRS duration and etiology of systolic dysfunction. On the basis of the
      available clinical trials, implantation of an ICD for primary prevention of death
      provides a 7.9% absolute mortality reduction (p = 0.003) in patients with left
      ventricular (LV) systolic dysfunction who were receiving optimized medical
      therapy. This finding was not sensitive to the exclusion of any individual trial.
      The ICD is an effective primary preventative measure in patients who are at risk
      for death; however, the application of this therapy needs to be individualized
      for the patient, similar to drug therapies in LV systolic dysfunction. In health
      care settings without unlimited resources, optimal use of this therapy will
      require better risk stratification methods or lowering of the initial device
      cost.

PMID- 15582315
TI  - Assessment of non-ST-segment elevation acute coronary syndromes with cardiac
      magnetic resonance imaging.
AB  - OBJECTIVES: The goal of this study was to determine: 1) if the presence of
      significant coronary stenosis in patients presenting with non-ST-segment
      elevation acute coronary syndromes (NSTE-ACS) can be predicted by cardiac
      magnetic resonance (CMR) imaging; and 2) if the analysis of several CMR methods
      improves its diagnostic yield compared with analysis of individual methods.
      BACKGROUND: With modern acquisition techniques, several CMR methods for the
      assessment of coronary artery disease (CAD) can be combined in a single
      noninvasive scanning session. Such a multicomponent CMR examination has not
      previously been applied to a large patient population, in particular those with a
      high prevalence of CAD in an acute situation. METHODS: Sixty-eight patients
      presenting with NSTE-ACS underwent CMR imaging of myocardial function, perfusion
      (rest and adenosine-stress), viability (by late contrast enhancement), and
      coronary artery anatomy. Visual analysis of CMR was carried out. First, all CMR
      data were reviewed in combination ("comprehensive analysis"). In further separate
      analyses, each CMR method was analyzed individually. The ability of CMR to detect
      coronary stenosis >/=70% on X-ray angiography was determined. RESULTS:
      Comprehensive CMR analysis yielded a sensitivity of 96% and a specificity of 83%
      to predict the presence of significant coronary stenosis and was more accurate
      than analysis of any individual CMR method; CMR was significantly more sensitive
      and accurate than the Thrombolysis In Myocardial Infarction risk score (p <
      0.001). CONCLUSIONS: Cardiac magnetic resonance imaging accurately predicts the
      presence of significant CAD in patients with NSTE-ACS. In this study, a
      comprehensive analysis of several CMR methods improved the accuracy of the test.

PMID- 15582316
TI  - The comprehensive approach to ischemic heart disease by cardiovascular magnetic
      resonance imaging: are we there yet?

PMID- 15582317
TI  - Comparative accuracy of real-time myocardial contrast perfusion imaging and wall
      motion analysis during dobutamine stress echocardiography for the diagnosis of
      coronary artery disease.
AB  - OBJECTIVE: This study sought to compare the accuracy of myocardial contrast
      echocardiography (MCE) and wall motion analysis (WMA) during submaximal and peak
      dobutamine stress echocardiography (DSE) for the diagnosis of coronary artery
      disease (CAD). BACKGROUND: The relative merits of MCE and WMA for the detection
      of CAD during DSE have not been studied in a large number of patients. METHODS:
      We studied 170 patients who underwent dobutamine (up to 50 microg/kg/min)
      atropine stress testing and coronary angiography. The WMA and MCE (using repeated
      boluses of Optison [Mallinckrodt, St. Louis, Missouri] or Definity [Bristol-Myers
      Squibb, New York, New York]) were performed at rest, at intermediate stress (65%
      to 75% of maximal heart rate), and at peak stress. The diagnosis of CAD (>/=50%
      stenosis in >/=1 coronary artery) was based on reversible wall motion and
      perfusion abnormalities. RESULTS: Coronary artery disease was detected in 127
      (75%) patients. Sensitivity of MCE was higher than that of WMA at maximal stress
      (91% vs. 70%; p = 0.001) and at intermediate stress (84% vs. 20%; p = 0.0001).
      Specificity was lower for MCE compared with WMA (51% vs. 74%; p = 0.01). Overall
      accuracy was higher for MCE than for WMA (81% vs. 71%; p = 0.01). Sensitivity for
      detection of CAD based on abnormalities in >/=2 vascular regions was higher for
      MCE than for WMA (67% vs. 28%; p < 0.01). CONCLUSIONS: The majority of inducible
      perfusion abnormalities occur at an intermediate phase of the stress test,
      without wall motion abnormalities. Myocardial contrast echocardiography provides
      better sensitivity than WMA, particularly in patients with submaximal stress and
      in identifying patients with multivessel CAD.

PMID- 15582319
TI  - Integration of cardiac magnetic resonance imaging with three-dimensional
      electroanatomic mapping to guide left ventricular catheter manipulation:
      feasibility in a porcine model of healed myocardial infarction.
AB  - OBJECTIVES: In a series of in vitro and in vivo experiments, we evaluated the
      feasibility of integrating three-dimensional (3D) magnetic resonance imaging
      (MRI) and electroanatomic mapping (EAM) data to guide real-time left ventricular
      (LV) catheter manipulation. BACKGROUND: Substrate-based catheter ablation of post
      myocardial infarction ventricular tachycardia requires delineation of the scarred
      myocardium, typically using an EAM system. Cardiac MRI might facilitate this
      procedure by localizing this myocardial scar. METHODS: A custom program was
      employed to integrate 3D MRI datasets with real-time EAM. Initially, a plastic
      model of the LV was used to determine the optimal alignment/registration
      strategy. To determine the in vivo accuracy of the registration process, ablation
      lesions were directed at iatrogenic MRI-visible "targets" (iron oxide injections)
      within normal porcine LVs (n = 5). Finally, this image integration strategy was
      assessed in a porcine infarction model (n = 6) by targeting ablation lesions to
      the scar border. RESULTS: The in vitro experiments revealed that registration of
      the LV alone results in inaccurate alignment due primarily to rotation along the
      chamber's long axis. Inclusion of the aorta in the registration process rectified
      this error. In the iron oxide injection experiments, the ablation lesions were
      1.8 +/- 0.5 mm from the targets. In the porcine infarct model, the catheter could
      be reliably navigated to the mitral valve annulus, and the ablation lesions were
      uniformly situated at the scar borders. CONCLUSIONS: These data suggest that
      registration of pre-acquired magnetic resonance images with real-time mapping is
      sufficiently accurate to guide LV catheter manipulation in a reliable and
      clinically relevant manner.

PMID- 15582318
TI  - Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
AB  - OBJECTIVES: We sought to explore the relationship between a Tcap gene (TCAP)
      abnormality and cardiomyopathy. BACKGROUND: Hypertrophic cardiomyopathy (HCM) and
      dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent
      genetic investigations have revealed that mutations of genes encoding Z-disc
      components, including titin and muscle LIM protein (MLP), are the primary cause
      of both HCM and DCM. The Z-disc plays a role in establishing the mechanical
      coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP
      complex serving as a mechanical stretch sensor. Tcap interacts with the
      calsarcin, which tethers the calcineurin to the Z-disc. METHODS: The TCAP was
      analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136
      patients with DCM (34 familial and 102 sporadic cases). Two different in vitro
      qualitative assays-yeast two-hybrid and glutathion S-transferase pull-down
      competition-were performed in order to investigate functional changes in Tcap's
      interaction with MLP, titin, and calsarcin-1 caused by the identified mutations
      and a reported DCM-associated mutation, R87Q. RESULTS: Two TCAP mutations, T137I
      and R153H, were found in patients with HCM, and another TCAP mutation, E132Q, was
      identified in a patient with DCM. It was demonstrated by the qualitative assays
      that the HCM-associated mutations augment the ability of Tcap to interact with
      titin and calsarcin-1, whereas the DCM-associated mutations impair the
      interaction of Tcap with MLP, titin, and calsarcin-1. CONCLUSIONS: These
      observations suggest that the difference in clinical phenotype (HCM or DCM) may
      be correlated with the property of altered binding among the Z-disc components.

PMID- 15582320
TI  - Cardiopulmonary resuscitation with a novel chest compression device in a porcine
      model of cardiac arrest: improved hemodynamics and mechanisms.
AB  - OBJECTIVES: The goal of this study was to determine the magnitude and mechanisms
      of hemodynamic improvement of an automated, load-distributing band device
      (AutoPulse, Revivant Corp., Sunnyvale, California) compared with conventional
      cardiopulmonary resuscitation (C-CPR). BACKGROUND: Improved blood flow during
      cardiopulmonary resuscitation (CPR) enhances survival from cardiac arrest.
      METHODS: AutoPulse CPR (A-CPR) and C-CPR were performed on 30 pigs (16 +/- 4 kg)
      1 min after induction of ventricular fibrillation. Aortic and right atrial
      pressures were measured with micromanometers. Regional flows were measured with
      microspheres; A-CPR and C-CPR were performed with 20% anterior-posterior chest
      compression, with (n = 10) and without (n = 10) epinephrine. A pressure
      transducer was advanced down the airways during chest compressions (n = 10), and
      magnetic resonance imaging (MRI) was performed. RESULTS: AutoPulse CPR improved
      coronary perfusion pressure (CPP) (aortic - right atrial pressure) without
      epinephrine (A-CPR 21 +/- 8 mm Hg vs. C-CPR 14 +/- 6 mm Hg, mean +/- SD, p <
      0.0001) and with epinephrine (A-CPR 45 +/- 11 mm Hg vs. C-CPR 17 +/- 6 mm Hg, p <
      0.0001). AutoPulse CPR improved myocardial flow without epinephrine and cerebral
      and myocardial flow with epinephrine (p < 0.05). AutoPulse CPR also produced
      greater myocardial flow at every CPP (p < 0.01). With A-CPR, high airway pressure
      was noted distal to the carina, which corresponded to an area of airway collapse
      on MRI, and which was not present with C-CPR. CONCLUSIONS: AutoPulse CPR improved
      hemodynamics over C-CPR in this pig model. AutoPulse CPR with epinephrine can
      produce pre-arrest levels of myocardial and cerebral flow. The improved
      hemodynamics with A-CPR appear to be mediated through airway collapse, which
      likely impedes airflow and helps maintain higher levels of intrathoracic
      pressure.

PMID- 15582321
TI  - Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy
      mutation cardiac troponin T-Q92 in switch on-switch off bigenic mice.
AB  - OBJECTIVES: The aim of this study was to establish reversibility of cardiac
      phenotypes in hypertrophic cardiomyopathy (HCM) by generating bigenic mice in
      which expression of the mutant transgene could be turned on and off as needed.
      BACKGROUND: Advances in molecular therapeutics could ultimately lead to therapies
      aimed at correcting the causal mutations. However, whether cardiac phenotypes,
      once established, are permanent, or could be reversed, if expression of the
      mutant protein is turned off, is unknown. METHODS: We generated ligand-inducible
      bigenic mice, turned on and off expression of cardiac troponin T-Q92 (cTnT-Q92),
      responsible for human HCM, and characterized molecular, histologic, and
      functional phenotypes. RESULTS: We established six lines and in dose-titration
      studies showed that treatment with 1,000 mug/kg of mifepristone consistently
      switched on cTnT-Q92 expression in the heart. Short-term (16 days) induced
      expression enhanced myocardial systolic function without changing myocardial
      cyclic adenosine monophosphate levels. Levels of PTEN, a regulator of cardiac
      function, phospho-protein kinase C-Zetalambda-Thr538 and phosphor-protein kinase
      D-Ser744-748 were reduced, whereas messenger ribonucleic acid (mRNA) levels of
      NPPA, NPPB, and sarcoplasmic reticulum calcium adenine triphosphatase 2 (ATP2A2)
      (hypertrophic markers) and procollagen COL1A1, COL1A2, and COL3A1 were unchanged.
      Long-term (70 days) induced expression increased COL1A1 and COL1A3 mRNAs levels
      and collagen volume fraction and reduced levels of NPPA and NPPB. Switching off
      expression of the cTnT-Q92 reversed functional, molecular, and histologic
      phenotypes completely. CONCLUSIONS: The initial phenotype induced by cTnT-Q92 is
      enhanced myocardial systolic function followed by changes in signaling kinases
      and interstitial fibrosis. Established phenotypes in HCM reverse upon turning off
      expression of the mutant protein. These findings provoke pursuing specific
      therapies directed at correcting the underlying the genetic defect in HCM.

PMID- 15582322
TI  - Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes:
      implications for herceptin-induced cardiomyopathy.
AB  - OBJECTIVES: We investigated the effects of erbB2 inhibition by anti-erbB2
      antibody on cardiomyocyte survival and mitochondrial function. BACKGROUND: ErbB2
      is an important signal integrator for the epidermal growth factor family of
      receptor tyrosine kinases. Herceptin, an inhibitory antibody to the erbB2
      receptor, is a potent chemotherapeutic but causes cardiac toxicity. METHODS:
      Primary cultures of neonatal rat ventricular myocytes were exposed to anti-erbB2
      antibody (Ab) (7.5 mug/ml) for up to 24 h. Cell viability, mitochondrial
      function, and apoptosis were measured using multiple complementary techniques.
      RESULTS: ErbB2 inhibition was associated with a dramatic increase in expression
      of the pro-apoptotic Bcl-2 family protein Bcl-xS and decreased levels of anti
      apoptotic Bcl-xL. There was a time-dependent increase in mitochondrial
      translocation and oligomerization of bcl-associated protein (BAX), as indicated
      by 1,6-bismaleimidohexane crosslinking. The BAX oligomerization was associated
      with cytochrome c release and caspase activation. These alterations induced
      mitochondrial dysfunction, a loss of mitochondrial membrane potential (psi) (76.9
      +/- 2.4 vs. 51.7 +/- 0.1; p < 0.05; n = 4), a 35% decline in adenosine
      triphosphate levels (p < 0.05), and a loss of redox capacity (0.72 +/- 0.04 vs.
      0.64 +/- 0.02; p< 0.01). Restoration of Bcl-xL levels through transactivating
      regulatory protein-mediated protein transduction prevented the decline in psi
      mitochondrial reductase activity and cytosolic adenosine triphosphate.
      CONCLUSIONS: Anti-erbB2 activates the mitochondrial apoptosis pathway through a
      previously undescribed modulation of Bcl-xL and -xS, causing impairment of
      mitochondrial function and integrity and disruption of cellular energetics.

PMID- 15582323
TI  - Mechanical unloading improves intracellular Ca2+ regulation in rats with
      doxorubicin-induced cardiomyopathy.
AB  - OBJECTIVES: We sought to assess whether mechanical unloading has beneficial
      effects on cardiomyocytes from doxorubicin-induced cardiomyopathy in rats.
      BACKGROUND: Mechanical unloading by a left ventricular assist device (LVAD)
      improves the cardiac function of terminal heart failure in humans. However,
      previous animal studies have failed to demonstrate beneficial effects of
      mechanical unloading in the myocardium. METHODS: The effects of mechanical
      unloading by heterotopic abdominal heart transplantation were evaluated in the
      myocardium from doxorubicin-treated rats by analyzing the intracellular free
      calcium level ([Ca(2+)](i)) and the levels of intracellular Ca(2+)-regulatory
      proteins. RESULTS: In doxorubicin-treated rats, the duration of cell shortening
      and [Ca(2+)](i) transients in cardiomyocytes was prolonged (432 +/- 28.2% of
      control in 50% relaxation time; 184 +/- 10.5% of control in [Ca(2+)](i) 50% decay
      time). Such prolonged time courses significantly recovered after mechanical
      unloading (114 +/- 10.4% of control in 50% relaxation time; 114 +/- 5.8% of
      control in 50% decay time). These effects were accompanied by an increase in
      sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) protein levels (0.97 +/- 0.05 in
      unloaded hearts vs. 0.41+/- 0.09 in non-unloaded hearts). The levels of other
      intracellular Ca(2+)-regulatory proteins (phospholamban and ryanodine receptor)
      were not altered after mechanical unloading in doxorubicin-treated hearts. These
      parameters in unloaded hearts without doxorubicin treatment were similar to
      normal hearts. CONCLUSIONS: Mechanical unloading increases functional
      sarcoplasmic reticulum Ca(2+) ATPase and improves [Ca(2+)](i) handling and
      contractility in rats with doxorubicin-induced cardiomyopathy. These beneficial
      effects of mechanical unloading were not observed in normal hearts.

PMID- 15582324
TI  - Magnetic resonance imaging-guided transcatheter implantation of a prosthetic
      valve in aortic valve position: Feasibility study in swine.

PMID- 15582325
TI  - Feasibility of adjusting paced left ventricular activation by manipulating
      stimulus strength.

PMID- 15582326
TI  - Torasemide inhibits transcardiac extraction of aldosterone in patients with
      congestive heart failure.

PMID- 15582327
TI  - Depression and heart failure.

PMID- 15582328
TI  - Influence of age, gender, and race on depression in heart failure patients.

PMID- 15582329
TI  - Depression in older adults with heart failure.

PMID- 15582332
TI  - Clinical efficacy of sildenafil in primary pulmonary hypertension.

PMID- 15582333
TI  - True uncomplicated obesity is not related to increased left ventricular mass and
      systolic dysfunction.

PMID- 15582335
TI  - ACCF/AHA/HRS/SCAI clinical competence statement on physician knowledge to
      optimize patient safety and image quality in fluoroscopically guided invasive
      cardiovascular procedures. A report of the American College of Cardiology
      Foundation/American Heart Association/American College of Physicians Task Force
      on Clinical Competence and Training.

PMID- 15582336
TI  - Educating and counseling children about physical health.

PMID- 15582337
TI  - Models and theories in studies on educating and counseling children about
      physical health: a systematic review.
AB  - The aim of this review is to gain a comprehensive view on the theories and models
      referred to in studies on educating and counseling children about physical
      health. A computer search was conducted using PubMed Medline, and Silverplatter
      Webspirs Psycinfo. Original studies, reviews, and theoretical papers published
      between 1992-2003 were included. The review presents the results of the 35
      studies in which the majority of the subjects were between 0 and 12 years of age.
      A classification system is proposed that helped grouping the models, and the
      interrelationship between this classification and the characteristics of the
      reviewed studies is explored. The classification could function as an
      introductory guide and help to select appropriate theories and models when
      defining future research agenda's. The results of this review may attribute to
      the refinement of the theoretical underpinning of child education and counseling
      in physical health.

PMID- 15582338
TI  - Counseling children with chronic physical illness.
AB  - We examine the needs of children with chronic physical illness and discuss how
      their needs may be met by counseling. Initially counseling is defined and
      boundaries with other activities established. Issues involved in counseling
      children with chronic illness are outlined and children's special needs regarding
      psychosocial issues discussed, with examples relating to asthma, cystic fibrosis,
      diabetes and epilepsy presented. Finally recommendations are made regarding
      counseling services.

PMID- 15582339
TI  - The role of effective communication with children and their families in fostering
      adherence to pediatric regimens.
AB  - Adherence to pediatric health enhancement, disease prevention, and medical
      treatment, particularly for chronic disease, can be challenging because of
      demanding regimens, children's progressing developmental stages, and varying
      family perspectives and relationships. This review examines adherence in the
      context of communication among providers, pediatric patients, and their families.
      The focus is on: the delivery of prevention and treatment information; trust in
      the therapeutic relationship; beliefs and attitudes in shaping acceptance of
      health care messages; social and cultural norms; building patient and family
      commitment to behavior change; family habits; barriers and pressures faced by
      patients and their families; the role of social networks and social support in
      fostering adherence, and the effects of family cohesiveness and family conflict.
      The unique challenges of fostering preventive health care and treatment for
      chronic disease in the context of transition to adolescence are also considered,
      and effective clinical solutions are reviewed.

PMID- 15582340
TI  - Unplanned smoking initiation: new insights and implications for interventions.
AB  - Despite intensive efforts, most smoking prevention interventions have had
      disappointing results. In the present paper, the assumption underlying these
      efforts that smoking initiation is the result of a rational decision or plan, is
      questioned. The process of adolescent smoking initiation is described, based on a
      recently conducted series of studies. It is argued that smoking initiation among
      adolescents is unplanned behaviour. Therefore, interventions regarding smoking
      initiation should not only include a focus on smoking-specific cognitions. Models
      that incorporate both conscious and unconscious processes need to be used in
      mapping smoking prevention efforts. Further, programmes that help adolescents to
      quit smoking need more attention. Finally, it is argued that smoking prevention
      interventions should aim at influencing the image of nonsmoking by using mass
      media interventions and restrictive policies.

PMID- 15582341
TI  - Psychosocial characteristics of obese children/youngsters and their families:
      implications for preventive and curative interventions.
AB  - A profile will be given of the psychosocial characteristics of obese children and
      youngsters, as well as those of their families. Then several attempts of
      (particularly) preventive interventions will be sketched. Differences found
      between clinical and non-clinical groups of obese children and youngsters do not
      permit generalized statements regarding specific psychosocial characteristics.
      Just as little as there exist a simple and unequivocal image of family
      functioning with these children. There are great differences between the
      psychological assumptions and the biological concepts about obesity. Whereas,
      biological concepts are relevant for the whole obese population, psychosocial
      characteristics seems to hold mainly for the clinical group of obese persons. The
      gap between clinical versus non-clinical as well as curative versus preventive
      approaches will be explained. There are remarkable differences between curative
      versus preventive intervention goals in terms of the extent to which they focus
      on life style habits or psychosocial (dys)functioning. Where prevention
      strategies focus more on enhancing physical activities, curative interventions
      focus more on changing eating behavior patterns and (depending on chronicity and
      seriousness of obesity) modifying psychosocial dysfunctioning.

PMID- 15582342
TI  - Illness through the eyes of the child: the development of children's
      understanding of the causes of illness.
AB  - In this study 158 children, 80 children with diabetes mellitus and 78 healthy
      classmates, were interviewed about their concept of different types of illness (a
      cold, diabetes, infection, the most and least serious disease) and illness
      related concepts (pain, becoming ill and going to the doctor or hospital).
      Special attention was given to the relationship between development of thinking
      and the variables anxiety, locus of control and family- and school functioning.
      The results show that the ideas of the children about the causes of illness
      follow a sequence of developmental stages, described as 'Through the Eyes of the
      Child' (TEC) model. Perception seems to be the child's central auto regulative
      system of cognitive development. The findings suggest that thinking about illness
      develops relatively independently of other influences. The practical relevance of
      knowing how children's thinking about illness develops is elaborated in terms of
      their implications for health education. Immature thoughts of children about
      illness can be detected and accepted and not dismissed as irrational. With the
      help of this model, health education of the child can be facilitated.

PMID- 15582343
TI  - Do pictograms improve children's understanding of medicine leaflet information?
AB  - There is a growing need for balanced drug information customized for special
      target groups such as children [Food and Drug Administration. Prescription Drug
      Product Labeling; Medication Guide Requirements; Proposed Rule. Part VII.
      Department of Health and Human Services, 21 CRF Part 201, et al. Federal Register
      1995;60:44182-252; Dickinson D, Raynor DK, Duman M. Patient information leaflets
      for medicines: using consumer testing to determine the most effective design.
      Patient Educ Couns 2001;43:147-59]. Pictograms are one aid that may be used to
      make information easier to read and understand. The aim of this study was to test
      whether children understand pictograms developed by the United States
      Pharmacopeia (USP) [The United States Pharmacopeial Convention Inc. USP
      Pictograms. Retrieved 11 March 2002 from http://www.usp.org/], and especially, if
      the pictograms improve children's understanding of medicine leaflet information.
      Finnish elementary school children aged 7 years (n=28), 11 years (n=31) and 13
      years (n=31) were interviewed and asked what they thought 15 USP pictograms mean.
      The two older age groups were also asked to read an "easy-to-read" leaflet for
      penicillin-V. Every second child was given a leaflet with a plain text and the
      others received the same text accompanied by pictograms. After reading the
      leaflet, the children were asked seven questions related to the text. Most of the
      children understood the meanings of the selected 15 pictograms correctly, the
      proportion of the correct explanations varying from 30 to 99% according to the
      pictogram. Even well-understood pictograms did not help the children understand
      the leaflet information, although they reduced the need for probing. This study
      shows that the context in which pictograms are tested makes a difference in the
      results. Testing plain pictograms without incorporating them in their real
      context, e.g., in the patient information leaflet may exaggerate their usefulness
      in leaflet information.

PMID- 15582344
TI  - Health promotion for survivors of childhood cancer: a minimal intervention.
AB  - We report the evaluation of an information booklet aimed to explain the purpose
      of follow-up to survivors of childhood cancer. Evaluations drew on theoretical
      concepts in the elaboration likelihood and stages of change models. We predicted
      that survivors who adopt central rather than peripheral processing would show
      greater understanding and increased readiness to change health behaviour. Forty
      eight survivors were shown an example page of the booklet in the clinic and then
      completed questionnaires about attitude to clinic, readiness to change behaviour,
      and the importance and scariness of the information. They were then given the
      whole booklet and asked to complete a second questionnaire at home. After reading
      the booklet, survivors reported a more positive attitude to clinic. Survivors
      using central processing rated information as more important and were more ready
      to change health behaviour than peripheral processors. We recommend that methods
      to encourage central processing should be routinely included when providing
      children with health information.

PMID- 15582345
TI  - The participation roles of children and adolescents in the dietary counseling of
      diabetics.
AB  - This paper analyses the production and reception roles of 7- to 9-year-old
      children and 13- to 15-year-old adolescents in two-party, three-party and multi
      party encounters in the dietary counseling of diabetics. In the two-party
      encounters, the adolescents had an active patient role, even though their
      engagement withered if they had to go through a long examination or if they were
      asked about a 'delicate issue'. In the three-party encounters, despite their good
      interactional competence, they often turned into withdrawn bystanders when the
      parent spoke on their behalf, complemented or corrected their talk. The 7- to 9
      year-old children were mostly silent and the mother spoke for them. However, they
      were ready to answer the questions that were clearly addressed to them.
      Furthermore, they had their own interaction patterns. Firstly, even when absorbed
      in their play, they sharply intervened in the adults' talk in order to correct an
      inaccurate detail. Secondly, they participated in the interaction in their
      playing. In the multi-party encounters with four or five participants, the more
      adult participants there were, the more marginalised role the child patient had.

PMID- 15582346
TI  - Asthma education: the adolescent experience.
AB  - Recent studies show that prevalence of asthma is higher among adolescents than
      children. Adolescents have poor asthma self-management skills resulting in a
      significant increase in the severity of asthma exacerbations and a reduction in
      their quality of life. Despite this, few self-management programs have been
      developed for adolescents. Adolescents experience developmental transitions that
      both hinder and facilitate asthma self-management. In this paper we discuss
      developmental transitions in cognition, knowledge, autonomy, identity
      development, and peer relations in terms of their influence on adolescents'
      management of asthma. Next, we describe the Asthma Self-Management for
      Adolescents (ASMA) program that incorporates developmental characteristics into
      an age-appropriate school-based asthma education program. Preliminary data is
      presented indicating that the program is successful in enrolling and engaging the
      interest of adolescents with persistent asthma.

PMID- 15582347
TI  - Changes in physical activity and psychosocial determinants of physical activity
      in children and adolescents treated for obesity.
AB  - The purpose of this study was to describe changes in physical activity and
      determinants in youngsters treated for obesity. Self-reported physical activity
      and determinants were assessed at start, during and after an intervention in 24
      obese patients (mean age 13.5+/-2.1 years). Participation in activities of
      moderate to high intensity increased during treatment, but 6-months after
      treatment this decreased again to pre-treatment levels. Participation in
      activities of low intensity and television watching decreased during treatment
      and increased following treatment. Very little change was found in perceived
      benefits, barriers or self-efficacy scores. Modelling of siblings decreased after
      treatment, whereas there was no evolution in modelling of parents. Social support
      by family members increased during treatment, but decreased following treatment.
      We can conclude that the intervention was successful in activating obese
      youngsters to move at the desirable exercise intensity and frequency; however,
      maintenance of the exercise habit after treatment was not successful.

PMID- 15582348
TI  - Poor adherence to self-medication instructions in children with asthma and their
      parents.
AB  - This study describes a self-treatment program for parents of children with
      asthma. The aim was to prevent asthma exacerbations by learning to recognise
      prodromal signs and acting upon them by increasing inhaled corticosteroids (ICS).
      The study questions were: (1) can we teach parents and children to recognise
      prodromal signs? (2) are instructions to increase inhalation medication followed?
      (3) will frequency and severity of asthma attacks diminish subsequently? Due to
      physicians' changed attitude towards prescription of ICS, fewer children could be
      recruited who were "ICS-naive" than expected. Twenty-nine children of the age of
      4-11 years with moderate asthma, participated in a one year prospective
      randomised study. Structured information was given to all patients on asthma,
      symptoms and medication. The experimental group received additional information
      on recognising prodromal signs and doubling ICS during one week. Only in 25% of
      the patients who recognised prodromal signs the dose of ICS was doubled (as
      prescribed), in 75% inadequately or not at all. Recognition of prodromal signs
      was poor as well as compliance to increase as-needed medication. No significant
      decrease of asthma symptoms occurred in the experimental group. Clinical
      implications are important for self-treatment instructions: an individually
      tailored and multi-component program should be offered by health care providers
      in order to help the patient to recognise early alarm symptoms, comply to self
      treatment instructions and to make adaptations for continuous self-regulation.

PMID- 15582349
TI  - Counseling children and parents about epilepsy.
AB  - In spite of remarkable progress in drug therapy, childhood and adolescent
      epilepsy is often a distressing condition lasting several years before possible
      recovery. Adaptation problems to the disease, and also to health recovery, are
      likely to occur. Stigma and discrimination may persist also after recovery.
      Learning problems involve a high number of patients. Neuropsychological problems
      related to localization of the epileptic focus may be present; intellectual
      deterioration in more severe cases and in some specific syndromes may occur.
      These problems are not unknown, but therapeutic effort is often directed only
      towards seizure control. The importance of counseling children and parents is
      stressed by the authors, and practical advice is given on planning doctor-patient
      dialogues, in order to prevent non-justified restrictions in day life, fears and
      negative reactions, and to ameliorate intrafamilial relation, integration in the
      school milieu and compliance towards drug intake. The role of neuropsychological
      evaluation and pedagogic advice is also emphasized. Children and adolescents with
      epilepsy and their families need more than medical therapeutic support to get an
      acceptable quality of life.

PMID- 15582350
TI  - Nitrofen induces a redox-dependent apoptosis associated with increased p38
      activity in P19 teratocarcinoma cells.
AB  - Nitrofen is a diphenyl ether herbicide that produces a spectrum of fetal
      abnormalities in rodents. To characterize the molecular mechanisms of nitrofen
      mediated birth defects at the cellular level, we explored its effects on
      undifferentiated P19 teratocarcinoma cells. Nitrofen induces a time-dependent
      cell death of P19 cells that is associated with increases in TUNEL-positivity and
      caspase-3 cleavage suggesting that nitrofen induces P19 cell apoptosis. In
      addition, the increase in TUNEL-positive cells was inhibited with zVAD-fmk,
      suggesting that nitrofen induces a caspase-dependent apoptosis. Nitrofen
      treatment was associated with increased p38 MAP kinase activity, though
      pretreatment of cells with multiple p38 inhibitors did not affect nitrofen
      mediated caspase-3 cleavage, suggesting caspase-3 cleavage is p38-independent.
      Nitrofen induced a dose-dependent increase in reactive oxygen species (ROS),
      which was accompanied by a decrease in the ratio of reduced/oxidized glutathione,
      indicating that nitrofen alters the cellular redox state of these cells.
      Furthermore, pretreatment of cells with N-acetyl cysteine gave a dose- and time
      dependent reduction of caspase-3 cleavage, supporting the observations that
      caspase-3 cleavage is cell-redox-dependent. Therefore, nitrofen induces P19 cell
      apoptosis that is cell-redox-dependent and is associated with increases in p38
      activity and ROS and may play a role in nitrofen-mediated birth defects.

PMID- 15582351
TI  - Analysis of oxidative stress in SK-N-MC neurons exposed to styrene-7,8-oxide.
AB  - Styrene-7,8-oxide (SO) is the main metabolite of styrene, a neurotoxic volatile
      organic compound used industrially. Here we report the novel observation that
      several markers of oxidative stress were affected in SK-N-MC cells exposed for 16
      h to concentrations of SO that induce apoptotic cell death. The production of
      Thiobarbituric Acid Reactive Substances (TBARS), rose from 69.1 +/- 15.7 nmol/g
      protein (control) to 119.3 +/- 39.2 and 102.0 +/- 17.3 nmol/g protein after
      exposure to 0.3 and 1 mM SO, respectively. Carbonyl group levels were
      significantly enhanced by SO at both concentrations. The lower dose also
      decreased sulphydryl groups. SO caused a marked oxidative DNA damage, as shown by
      a fivefold increase in 8-hydroxy-2(')-deoxyguanosine (8-OHdG). In addition, SO
      exposure resulted in alterations of scavenging abilities, given the reduction of
      both glutathione (GSH) and glutathione-S-transferase (GST) activity. Induction of
      expression of the oxidative stress response gene heme-oxygenase-1 (HO-1) and an
      increased HO-1 activity were also observed. These data provide compelling
      evidence that oxidative stress significantly contributes to SO toxicity in
      neuronal cells.

PMID- 15582352
TI  - Effects of TCDD and estradiol-17beta on the proliferation and Na+/glucose
      cotransporter in renal proximal tubule cells.
AB  - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental
      toxicant that alters cell proliferation and function. Estrogens are noted for
      their ability to stimulate cell proliferation in various tissues. However, little
      is known about any interaction between TCDD and estradiol-17beta (E(2)) that
      affects renal proximal tubule cell proliferation and Na(+)/glucose
      cotransporters' activity. Thus, the effects of TCDD and E(2) on [(3)H]-thymidine
      incorporation and on alpha-methyl-d-glucopyranoside (alpha-MG) uptake were
      investigated in the primary rabbit kidney proximal tubule cells (PTCs). TCDD
      (>10(-10) M >1 h) inhibited [(3)H]-thymidine incorporation and c-fos transcripts
      in real-time RT-PCR, whereas E(2) (>10(-9) M, 24 h) stimulated them. Aryl
      hydrocarbon receptor (AhR) agonists, beta-naphthoflavone (beta-NF) and
      polychlorinated biphenyls (PCBs) (10(-6) M) synergistically increased the TCDD
      induced inhibition of [(3)H]-thymidine incorporation. However, the AhR
      antagonist, alpha-naphthoflavone (alpha-NF) as well as E(2) blocked TCDD-induced
      inhibition of [(3)H]-thymidine incorporation. TCDD (10(-8) M, 48 h) specifically
      inhibited alpha-MG uptake and its effect was due to V(max) value but not K(m)
      value. Indeed, TCDD decreased Na(+)/glucose cotransporter 1, 2 (SGLT1, 2) protein
      level compared with control. In addition, TCDD-induced inhibition of alpha-MG
      uptake was blocked by alpha-NF or E(2). In conclusion, TCDD inhibited [(3)H]
      thymidine incorporation and alpha-MG uptake, and E(2) blocked TCDDs effects in
      primary cultured renal proximal tubule cells.

PMID- 15582353
TI  - Heme oxygenase-1-mediated partial cytoprotective effect by NO on cadmium-induced
      cytotoxicity in C6 rat glioma cells.
AB  - Heme oxygenase-1 (HO-1) is a 32-kDa stress induced enzyme that degrades heme to
      carbon monoxide (CO) and biliverdin. By employing RT-PCR and Western blotting
      techniques, we have examined the HO-1 induction in C6 glioma cells that were
      treated with cadmium chloride (CdCl(2)) or spermine NONOate (SPER/NO). By
      employing a cell viability assay, we have also examined the cytoprotective effect
      of HO-1 induction against the cytotoxicity caused by toxic dose of CdCl(2). In C6
      glioma cells exposed to CdCl(2), expression of HO-1 (mRNA and protein) was
      increased in a dose- and time-dependent manner. Nitric oxide (NO) generated from
      SPER/NO very rapidly increased HO-1 mRNA expression in the C6 glioma cells. The
      induction of HO-1 by SPER/NO protected the cells from toxic dose of CdCl(2). The
      up-regulation of HO-1 mRNA expression by CdCl(2) was inhibited by a pre
      incubation of the cells with actinomycin D, a potent inhibitor of mRNA
      transcription. Upon the inhibition of elevated HO-1 mRNA expression by the use of
      zinc protoporphyrin IX (ZnPP), an inhibitor of HO activity, the change of HO-1
      mRNA expression by ZnPP was not observed. Thus, the glial cell may respond to
      CdCl(2) toxicity by enhancing the HO-1 expression in its effort to minimize the
      CdCl(2)-derived oxidative damage, and to survive. In the glioma cells, when the
      HO-1 expression was elevated by a prior incubation with SPER/NO, the cell
      viability against the cytotoxicity of CdCl(2) was significantly increased. When
      the results of our experiment are taken together, we discovered that NO provided
      a rapid enhancement of HO-1 expression, and it provided a protective effect
      against CdCl(2)-derived oxidative injury in the C6 rat glioma cells.

PMID- 15582354
TI  - Pyrrolizidine alkaloid clivorine induces apoptosis in human normal liver L-02
      cells and reduces the expression of p53 protein.
AB  - Clivorine, a pyrrolizidine alkaloid, is a potent toxic compound extracted from a
      Chinese medicinal plant Ligularia hodgsonii Hook. We have previously shown that
      clivorine inhibited human normal liver L-02 cells proliferation and induced p38
      mitogen-activated protein kinase phosphorylation. The aim of this study is to
      further observe the mechanism of clivorine-inhibited L-02 cells growth. In this
      paper we show here that clivorine can induce apoptosis in L-02 cells, reduce the
      expression of p53 protein but has no effect on the expression of Bcl-2 protein,
      and clivorine also induces the cleavage of the poly(ADP-ribose) polymerase in L
      02 cells. Our results suggest that the anti-proliferative function of clivorine
      in L-02 cells may be due to its inducing cell apoptosis, and clivorine-induced
      cell apoptosis is independent of p53 protein.

PMID- 15582355
TI  - In vitro metabolism and toxicity assessment of toxin T-514 (Peroxisomicine A1) of
      Karwinskia humboldtiana in microsomes and primary cultured hepatocytes.
AB  - T-514 (Peroxisomicine A(1)) from Karwinskia humboldtiana is a dimeric
      hydroxyanthracenone with a highly selective cytotoxic effect on tumor cells. We
      evaluated the metabolism of this compound in two in vitro systems (liver
      microsomes and hepatocytes) and assessed the cytotoxicity of its metabolites on
      normal and tumor cells. Microsomes (12.5, 125 and 250 microg of protein/ml) and
      hepatocytes (1 x 10(6) cells/ml) were incubated with the toxin (25 microM) for
      0.5, 1, 3, 6, 9, 12 and 24 h and the samples were examined using chromatographic
      analysis and UV spectra. Two metabolites (M1 and M2) were detected in the rat
      microsomes and one (M1) in the monkey microsomes. The retention times and UV
      spectra of the peaks were very similar to those of the toxin T-514. M1 was
      isolated and identified as a mixture of two isomers. The cytotoxicity of the
      metabolites was evaluated in Chang liver and Hep G2 cells but they did not show
      the selective cytotoxic effect on tumor cells seen in the original compound.

PMID- 15582356
TI  - Effects of ozone on isolated peripheral blood mononuclear cells.
AB  - We have investigated the release of cytokines from isolated peripheral human
      blood mononuclear cells (PBMC) exposed to various ozone concentrations for 10 min
      and the release of both proinflammatory and immunosuppressive cytokine after 24,
      48 and 76 h incubation. Ozonation was performed by exposing for 10 min equal cell
      numbers and volumes of cell suspension to equal volumes of a gas mixture (1:1
      ratio) composed of oxygen-ozone with precise ozone concentrations ranging from
      1.0 up to 80 microg/ml (0.02 up to 1.68 mM). Markers of oxidative stress showed a
      significant relationship between ozone doses and both lipid peroxidation and
      protein thiol groups content. With the exception of the lowest ozone
      concentration, the cytokine production of PBMC was depressed particularly at
      concentrations from 40 mug/ml upwards. There was no significant effect on IL-6
      production between exposed or unexposed cells, up to 72 h of incubation. IL-4
      production was markedly affected by ozone exposure, showing a marked decrease
      even at the lowest ozone concentration (2.5 microg/ml) already after 24 h
      incubation. On the other hand, production of IFN-gamma and TNF-alpha was slightly
      stimulated by the lowest ozone dose either at all times or only after 72 h
      incubation, respectively. Analysis of the proliferation index (PI) is consistent
      with these results showing that, while the lowest concentration stimulates it,
      progressively increasing O(3) concentrations inhibit the PI. These data show that
      there is a significant relationship between cytokine production and ozone
      concentrations and that PBMC are very sensitive to oxidation particularly in
      presence of serum with low antioxidant capacity.

PMID- 15582357
TI  - Genotoxic potential of cyproterone acetate: a possible role of reactive oxygen
      species.
AB  - The genotoxicity of cyproterone acetate was studied in human lymphocytes using
      chromosomal aberrations (CAs), mitotic index (MI) and sister chromatid exchanges
      (SCEs) as a parameter. Cyproterone acetate was found to be genotoxic at 20 and 30
      microM. To study the possible mechanism of the genotoxicity of cyproterone
      acetate, superoxide dismutase (SOD) and catalase (CAT) were used separately and
      in combination along with the 30 microM of cyproterone acetate at different
      doses. SOD treatment increases CAs, SCEs and decreases MI as compared to
      treatment with 30 microM CPA alone, at both of the tested doses. CAT treatment
      decreases the frequencies of CAs and SCEs and increases MI in both, as compared
      to treatment with 30 microM CPA alone, separately and in combination with SOD,
      suggesting a possible role of reactive oxygen species for the genotoxic damage.

PMID- 15582358
TI  - Comparative studies on the effects of water, ethanol and water/ethanol mixtures
      on chemical partitioning into porcine stratum corneum and silastic membrane.
AB  - The effects of water and ethanol vehicles on stratum corneum and silastic
      membrane partitioning of 11 industrial and agricultural compounds were studied to
      aid in characterizing and assessing risk from skin exposure. Zero percent, 50%
      and 100% aqueous ethanol solutions were used as solvents for (14)C labeled
      phenol, 4-nitrophenol, pentachlorophenol, dimethyl parathion, parathion,
      chloropyrifos, fenthion, triazine, atrazine, simazine and propazine. Compound
      partitioning between the solvents and porcine stratum corneum/silastic membrane
      were estimated. Stratum corneum was exposed to aqueous ethanol ranging from 0% to
      100% v/v ethanol in 20% increments and Fourier transform infrared spectroscopy
      (FT-IR) was used to obtain an index of lipid disorder. Gravimetry and FT-IR were
      used to demonstrate lipid extraction in aqueous ethanol solutions. Partitioning
      patterns in silastic membranes resembled those in stratum corneum and were
      correlated with octanol/water partitioning. Partitioning was highest in water and
      was higher from 50% ethanol than from 100% ethanol, except for parathion, 4
      nitrophenol, atrazine and propazine. Correlation existed between molecular weight
      and partitioning in water, but not in ethanol and ethanol/water mixtures. Lipid
      order, as reflected in FT-IR spectra, was not altered. These studies suggest that
      stratum corneum partitioning of the compounds tested is primarily determined by
      relative compound solubility between the stratum corneum lipids and the donor
      solvent. Linear relationships existed between octanol/water partitioning and
      stratum corneum partitioning. Partitioning was also correlated with molecular
      weight in water solvent systems, but not in ethanol and ethanol/water mixtures.
      Ethanol and ethanol/water mixtures altered the stratum corneum through lipid
      extraction, rather than through disruption of lipid order.

PMID- 15582359
TI  - Refinement of the Slug Mucosal Irritation test as an alternative screening test
      for eye irritation.
AB  - The objective of this study was to limit the test procedure time of the Slug
      Mucosal Irritation test to one day and to determine whether it is a relevant and
      reliable method to predict the eye irritation potential of chemicals. The
      irritation potential of several eye reference chemicals can be estimated by the
      amount of mucus produced when tested at a 1% concentration (60 min). Since some
      in vivo irritating chemicals did not influence this endpoint the effect of
      increasing concentrations on membrane damage was investigated. This study
      revealed that when tested at a 3.5% concentration (60 min) the underestimated
      chemicals induced an increased protein and/or enzyme release. A two-step
      classification prediction model was developed that classified the chemicals first
      by the amount of mucus produced (1%, 60 min). Chemicals that did not affect this
      endpoint were classified based on the membrane damage induced by a second
      treatment (3.5%, 60 min). The results were compared with the corresponding EU
      classification (NI, R36 and R41) and 71% of the chemicals were correctly
      classified with a specificity and sensitivity of 75% and 94%, respectively.
      Repeated testing of the chemicals revealed a good intra-laboratory
      reproducibility. The test seems to be a promising method for screening the eye
      irritating potential of chemicals.

PMID- 15582360
TI  - The amoebicidal aqueous extract from Castela texana possesses antigenotoxic and
      antimutagenic properties.
AB  - Due to long-term treatment toxicity and clinical resistance to drugs commonly
      used against E. histolytica, new drugs against amoebiasis are urgently needed.
      Castela texana ("chaparro amargo") is a shrub taken traditionally in teas and
      capsules of dry plant to treat intestinal amoebic infections. An aqueous extract
      was prepared and its mutagenic, genotoxic and cytotoxicity properties were
      evaluated in prokaryotic and eukaryotic systems. This extract was neither
      mutagenic when evaluated with the Ames test in Salmonella typhimurium strains
      TA98, TA100 and TA102, nor genotoxic in unscheduled DNA synthesis in hepatocyte
      cultures, even at the highest concentrations tested. In fact, C. texana extract
      showed antimutagenic activity on S. typhimurium strains TA98 and TA100 in the
      Ames test. Furthermore, it was capable of protecting liver cell cultures against
      unscheduled DNA synthesis induced by 2-acetylaminofluorene at a concentration of
      6.77 microg/ml. A free-radical scavenging test was used in order to explore the
      antioxidant capacity of C. texana extract with S. typhimurium strain TA102
      pretreated with norfloxacin, a free radical producer. This extract showed a free
      radical withdrawal effect. The effective chemoprotective activity of this extract
      could be due to the antioxidant capacity of the C. texana extract components. In
      this paper it is shown that the antiamoebic natural product, C. texana, is also
      antimutagenic and protects against induction of preneoplastic lesions in rat
      liver. These results justify further studies to extend it use to human beings.

PMID- 15582361
TI  - A new approach for the assessment of acrylamide toxicity using a green
      paramecium.
AB  - Exposure to acrylamide induces neurotoxic effects in humans. In addition, it
      induces genotoxic, reproductive and carcinogenic effects in laboratory animals.
      However, no convenient bioassay system for assessing acrylamide toxicity to
      animal and plant cells has been proposed to date. The present study aims to
      evaluate acrylamide toxicity to a green paramecium, Paramecium bursaria, bearing
      many endosymbiotic algae, because some chemicals are highly toxic to paramecia or
      microalgae, and some protozoa are already used for evaluation of environmental
      contaminations. Results showed that high acrylamide concentrations (> or = 1500
      mg/l) have a lethal effect on P. bursaria. Although low acrylamide concentrations
      (< or = 150 mg/l) induced less change on the paramecium growth, the number of
      endosymbiotically growing algal cells drastically decreased. The acrylamide
      concentration required to induce a 50% decrease in the cell number (IC(50)) was
      determined to be 7.8 mg/l for endosymbiotic algae, indicating that the algal
      sensitivity to acrylamide was 7 and 15 times higher than that of Syrian hamster
      embryo (SHE) cells and the host cells, respectively. Here, we propose the use of
      P. bursaria being a convenient and sensitive bioindicator as a new approach for
      the assessment of acrylamide toxicity.

PMID- 15582362
TI  - The use of human nasal in vitro cell systems during drug discovery and
      development.
AB  - The nasal route is widely used for the administration of drugs for both topical
      and systemic action. At an early stage in drug discovery and during the
      development process, it is essential to gain a thorough insight of the nasal
      absorption potential, metabolism and toxicity of the active compound and the
      components of the drug formulation. Human nasal epithelial cell cultures may
      provide a reliable screening tool for pharmaco-toxicological assessment of
      potential nasal drug formulations. The aim of this review is to give an overview
      of the information relevant for the development of a human nasal epithelial cell
      culture model useful during drug discovery and development. A primary goal in the
      development of in vitro cell culture systems is to maintain differentiated
      morphology and biochemical features, resembling the original tissue as closely as
      possible. The potential and limitations of the existing in vitro human nasal
      models are summarized. The following topics related to cell culture methodology
      are discussed: (i) primary cultures versus cell lines; (ii) cell-support
      substrate; (iii) medium and medium supplements; and (iv) the air-liquid interface
      model versus liquid-liquid. Several considerations with respect to the use of in
      vitro systems for pharmaceutical applications (transport, metabolism, assessment
      of ciliary toxicity) are also discussed.

PMID- 15582363
TI  - Characterization of phagolysosomal simulant fluid for study of beryllium aerosol
      particle dissolution.
AB  - A simulant of phagolysosomal fluid is needed for beryllium particle dissolution
      research because intraphagolysosomal dissolution is believed to be a necessary
      step in the cellular immune response associated with development of chronic
      beryllium disease. Thus, we refined and characterized a potassium hydrogen
      phthalate (KHP) buffered solution with pH 4.55, termed phagolysosomal simulant
      fluid (PSF), for use in a static dissolution technique. To characterize the
      simulant, beryllium dissolution in PSF was compared to dissolution in the J774A.1
      murine cell line. The effects of ionic composition, buffer strength, and the
      presence of the antifungal agent alkylbenzyldimethylammonium chloride (ABDC) on
      beryllium dissolution in PSF were evaluated. Beryllium dissolution in PSF was not
      different from dissolution in the J774A.1 murine cell line (p = 0.78) or from
      dissolution in another simulant having the same pH but different ionic
      composition (p = 0.73). A buffer concentration of 0.01-M KHP did not appear
      adequate to maintain pH under all conditions. There was no difference between
      dissolution in PSF with 0.01-M KHP and 0.02-M KHP (p = 0.12). At 0.04-M KHP,
      beryllium dissolution was increased relative to 0.02-M KHP (p = 0.02). Use of a
      0.02-M KHP buffer concentration in the standard formulation for PSF provided
      stability in pH without alteration of the dissolution rate. The presence of ABDC
      did not influence beryllium dissolution in PSF (p = 0.35). PSF appears to be a
      useful and appropriate model of in vitro beryllium dissolution when using a
      static dissolution technique. In addition, the critical approach used to evaluate
      and adjust the composition of PSF may serve as a framework for characterizing PSF
      to study dissolution of other metal and oxide particles.

PMID- 15582364
TI  - A rapid screening method to test apoptotic synergisms of ochratoxin A with other
      nephrotoxic substances.
AB  - The body may be exposed simultaneously to more than one nephrotoxic substance and
      to measure the effects of the great number of possible combinations of
      nephrotoxins will rapidly become a great challenge when using the traditional
      methods. Therefore, we developed a rapid and cost-efficient method to screen the
      apoptotic potential of combinations of known cell- or nephrotoxic substances as
      ochratoxin A (OTA), cisplatin, cadmium, H(2)O(2), and amphotericin B on renal
      epithelial cell lines. The cells were seeded in 96-well plates and the apoptotic
      and necrotic potential of different combinations of nephrotoxins was determined.
      We found different results for the combinations used: depending on the
      concentrations of the various substances, antagonistic, additive, or potentiating
      effects on caspase-3 activity were found after co-exposure to OTA. We conclude
      that the co-exposure of renal cells to OTA with other substances can enhance or
      reduce the apoptotic potential of one substance alone depending on the substance,
      the concentration and on the cell line investigated. A "harmless" substance can
      thus convert to a potent cell toxic substance when combined with OTA or vice
      versa. The underlying mechanisms of the synergistic effects remain unknown.

PMID- 15582365
TI  - Tooth slice organ culture and established cell line culture models for
      cytotoxicity assessment of dental materials.
AB  - The aim was to compare the use of different cell-material contact test methods
      with two different biological systems (cell line and tooth slice cultures) for
      cytotoxicity assessment of dental materials. Cytotoxicity of composites
      polymerized with two halogen-based and two light-emitting diode (LED) light
      curing units (LCUs) served as the basis for comparison. Disk shaped specimens (7
      x 2 mm) were fabricated using the four light sources. Composites were tested
      using L-929 cell line using direct/indirect/extract tests in accordance to
      standard protocols. Cytotoxicity was assessed using neutral red uptake. Tooth
      slice organ cultures were also employed to test the dental materials using
      direct/indirect test methods. Histomorphometric cell counting of intact
      odontoblasts and pulp fibroblasts and the use of tetrazolium salt 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were applied
      for cytotoxicity evaluation. Discrepancy in result presentation was observed in
      the different tests used with L-929. Sensitivity levels of the L-929 tests ranked
      as follows: extract test < direct contact test < indirect contact test. Tooth
      slice tests confirmed that L-929 direct contact test proved to be the most
      reliable test among the three. In conclusion, this study highlights the risk
      involved when relying on a single test method for cytotoxicity assessment. It
      would be advisable to test different culture models and then proceed using more
      clinically relevant biological system that stimulate the in vivo situation for
      confirmation.

PMID- 15582367
TI  - Pacemaker neurons and neuronal networks: an integrative view.
AB  - Rhythmically active neuronal networks give rise to rhythmic motor activities but
      also to seemingly non-rhythmic behaviors such as sleep, arousal, addiction,
      memory and cognition. Many of these networks contain pacemaker neurons. The
      ability of these neurons to generate bursts of activity intrinsically lies in
      voltage- and time-dependent ion fluxes resulting from a dynamic interplay among
      ion channels, second messenger pathways and intracellular Ca2+ concentrations,
      and is influenced by neuromodulators and synaptic inputs. This complex intrinsic
      and extrinsic modulation of pacemaker activity exerts a dynamic effect on network
      activity. The nonlinearity of bursting activity might enable pacemaker neurons to
      facilitate the onset of excitatory states or to synchronize neuronal ensembles-
      an interactive process that is intimately regulated by synaptic and modulatory
      processes.

PMID- 15582368
TI  - Persistent neural activity: prevalence and mechanisms.
AB  - Persistent neural activity refers to a sustained change in action potential
      discharge that long outlasts a stimulus. It is found in a diverse set of brain
      regions and organisms and several in vitro systems, suggesting that it can be
      considered a universal form of circuit dynamics that can be used as a mechanism
      for short-term storage and accumulation of sensory or motor information. Both
      single cell and network mechanisms are likely to co-operate in generating
      persistent activity in many brain areas.

PMID- 15582369
TI  - Functional diversity and specificity of neostriatal interneurons.
AB  - The firing of neostriatal spiny neurons in response to an excitatory input is
      modulated and sculpted by a variety of factors. Neostriatal interneurons are
      phenotypically diverse and have properties that enable them to specifically, but
      differentially, influence the activity of spiny neurons. Each of the three types
      of GABAergic interneurons produces a strong inhibitory postsynaptic potential in
      spiny neurons, the function of which is probably to influence the precise timing
      of action potential firing in either individual or ensembles of spiny neurons. By
      contrast, the role of cholinergic interneurons is to modulate the sub- and supra
      threshold responses of spiny neurons to cortical and/or thalamic excitation,
      particularly in reward-related activities. Both classes of interneurons are
      important sites of action of neuromodulators in neostriatum, and act in different
      but complementary ways to modify the activity of the spiny projection neurons.

PMID- 15582370
TI  - Learning in sensorimotor circuits.
AB  - The study of plasticity in the central nervous system is a major and very dynamic
      neuroscience research field with enormous clinical potential. Considerable
      advances in this field have been made during the past 10 years. It now appears
      that most circuits in the brain and spinal cord show plasticity and that they can
      be modified by experience. Knowledge of the mechanisms of plasticity in the
      nervous system is therefore essential for the understanding of how the nervous
      system is wired during development and how it adapts in response to changes in
      the body and environment. Recent findings indicate that functional sensorimotor
      modules probe the sensory signals from the body that are generated as a
      consequence of module specific activity and use this sensory feedback to
      calibrate the strength in its input-output connections. This experience-dependent
      signal adapts the circuitry in the sensorimotor module to the body anatomy and
      biomechanics.

PMID- 15582371
TI  - Sensory signals during active versus passive movement.
AB  - Our sensory systems are simultaneously activated as the result of our own actions
      and changes in the external world. The ability to distinguish self-generated
      sensory events from those that arise externally is thus essential for perceptual
      stability and accurate motor control. Recently, progress has been made towards
      understanding how this distinction is made. It has been proposed that an internal
      prediction of the consequences of our actions is compared to the actual sensory
      input to cancel the resultant self-generated activation. Evidence in support of
      this hypothesis has been obtained for early stages of sensory processing in the
      vestibular, visual and somatosensory systems. These findings have implications
      for the sensory-motor transformations that are needed to guide behavior.

PMID- 15582372
TI  - Genes and photons: new avenues into the neuronal basis of behavior.
AB  - A convergence of advances in optical methods and a better understanding of the
      genetics of development promise to revolutionize the study of neuronal circuits
      and their links to behavior. One of the great challenges in systems neurobiology
      has been to monitor and perturb activity in populations of identified neurons in
      vivo. Recent work has begun to achieve this goal through a combination of modern
      imaging methods with genetic labeling and perturbation.

PMID- 15582373
TI  - Contributions of functional imaging to understanding parkinsonian symptoms.
AB  - Brain imaging experiments identify plausible circuits involved in the genesis of
      the cardinal symptoms of Parkinson's disease. Akinesia is linked to
      hypoactivation of the supplementary motor area secondary to insufficient
      thalamocortical facilitation. Overactivation in other areas such as the lateral
      premotor and parietal cortex probably represents a compensatory mechanism.
      Bradykinesia is associated with abnormal functioning within intrinsic basal
      ganglia circuitry for scaling movements to appropriate magnitude. Parkinson's
      disease tremor is localized to pontine- and mesencephalic-cerebellar-thalamic
      circuits, with abnormalities of both dopamine and serotonin neurotransmission.
      There is a need to understand the anatomic intersections where information is
      shared across these circuits.

PMID- 15582374
TI  - Selecting the signals for a brain-machine interface.
AB  - Brain-machine interfaces are being developed to assist paralyzed patients by
      enabling them to operate machines with recordings of their own neural activity.
      Recent studies show that motor parameters, such as hand trajectory, and cognitive
      parameters, such as the goal and predicted value of an action, can be decoded
      from the recorded activity to provide control signals. Neural prosthetics that
      use simultaneously a variety of cognitive and motor signals can maximize the
      ability of patients to communicate and interact with the outside world. Although
      most studies have recorded electroencephalograms or spike activity, recent
      research shows that local field potentials (LFPs) offer a promising additional
      signal. The decode performances of LFPs and spike signals are comparable and,
      because LFP recordings are more long lasting, they might help to increase the
      lifetime of the prosthetics.

PMID- 15582376
TI  - Closing the loop between neurobiology and flight behavior in Drosophila.
AB  - Fruit flies alter flight direction by generating rapid stereotyped turns called
      saccades. Using a combination of tethered and free-flight methods, both the
      aerodynamic mechanisms and the sensory triggers for saccades have been
      investigated. The results indicate that saccades are elicited by visual
      expansion, and are brought about by remarkably subtle changes in wing motion.
      Mechanosensory feedback from the fly's 'gyroscope' complements visual cues to
      terminate saccades, as well as to stabilize forward flight. Olfactory stimuli
      elicit tonic increases in wingbeat amplitude and frequency but do not alter the
      time course or magnitude of visual reflexes.

PMID- 15582377
TI  - An engram found? Evaluating the evidence from fruit flies.
AB  - Is it possible to localize a memory trace to a subset of cells in the brain? If
      so, it should be possible to show: first, that neuronal plasticity occurs in
      these cells. Second, that neuronal plasticity in these cells is sufficient for
      memory. Third, that neuronal plasticity in these cells is necessary for memory.
      Fourth, that memory is abolished if these cells cannot provide output during
      testing. And fifth, that memory is abolished if these cells cannot receive input
      during training. With regard to olfactory learning in flies, we argue that the
      notion of the olfactory memory trace being localized to the Kenyon cells of the
      mushroom bodies is a reasonable working hypothesis.

PMID- 15582378
TI  - Unconventional sex: fresh approaches to courtship learning.
AB  - Understanding the complex array of genes, proteins and cells involved in learning
      and memory is a major challenge for neuroscientists. Using the genetically
      powerful model system, Drosophila melanogaster, and its well-studied courtship
      behavior, investigators have begun to delineate essential elements of associative
      and nonassociative behavioral plasticity. Advances in transgenic tools and
      developments in behavioral assays have increased the power of studying courtship
      learning in the fruit fly.

PMID- 15582379
TI  - Vocal communication in frogs.
AB  - The robust nature of vocal communication in frogs has long attracted the
      attention of natural philosophers and their biologically inclined successors.
      Each frog species produces distinctive calls that facilitate pre-mating
      reproductive isolation and thus speciation. In many terrestrial species, a chorus
      of simultaneously calling males attracts females to breeding sites; reproductive
      females then choose and locate one male, using distinctive acoustic cues. Males
      compete with each other vocally and sometimes physically as well. Anuran acoustic
      signaling systems are thus subject to the strong pressures of sexual selection.
      We are beginning to understand the ways in which vocal signals are produced and
      decoded by the nervous system and the roles of neurally active hormones in both
      processes.

PMID- 15582380
TI  - Signal acquisition and analysis for cortical control of neuroprosthetics.
AB  - Work in cortically controlled neuroprosthetic systems has concentrated on
      decoding natural behaviors from neural activity, with the idea that if the
      behavior could be fully decoded it could be duplicated using an artificial
      system. Initial estimates from this approach suggested that a high-fidelity
      signal comprised of many hundreds of neurons would be required to control a
      neuroprosthetic system successfully. However, recent studies are showing hints
      that these systems can be controlled effectively using only a few tens of
      neurons. Attempting to decode the pre-existing relationship between neural
      activity and natural behavior is not nearly as important as choosing a decoding
      scheme that can be more readily deployed and trained to generate the desired
      actions of the artificial system. These artificial systems need not resemble or
      behave similarly to any natural biological system. Effective matching of discrete
      and continuous neural command signals to appropriately configured device
      functions will enable effective control of both natural and abstract artificial
      systems using compatible thought processes.

PMID- 15582381
TI  - Functional microcircuitry in the accumbens underlying drug addiction: insights
      from real-time signaling during behavior.
AB  - An understanding of the neurobiological basis of drug addiction requires
      examination of real-time (subsecond) cellular and chemical responses in the brain
      reward system during drug-seeking and drug-taking behavior. Electrophysiological
      and electrochemical studies in the rodent nucleus accumbens have examined changes
      in cell firing and rapid dopamine signaling during crucial periods of behavioral
      responding for drugs, and show the associative nature of those signals. These
      findings are considered with respect to the functional microcircuitry in the
      nucleus accumbens that underlies goal-directed behavior and the role of this
      circuit in drug addiction.

PMID- 15582382
TI  - Reward representations and reward-related learning in the human brain: insights
      from neuroimaging.
AB  - This review outlines recent findings from human neuroimaging concerning the role
      of a highly interconnected network of brain areas including orbital and medial
      prefrontal cortex, amygdala, striatum and dopaminergic mid-brain in reward
      processing. Distinct reward-related functions can be attributed to different
      components of this network. Orbitofrontal cortex is involved in coding stimulus
      reward value and in concert with the amygdala and ventral striatum is implicated
      in representing predicted future reward. Such representations can be used to
      guide action selection for reward, a process that depends, at least in part, on
      orbital and medial prefrontal cortex as well as dorsal striatum.

PMID- 15582383
TI  - Vasopressin, oxytocin and social behaviour.
AB  - Understanding the neurobiology of social behaviour in mammals has been
      considerably advanced by the findings from two species of vole, one of which is
      monogamous and pair bonds whereas the other species is promiscuous and fails to
      form any long-lasting social relationships. The combination of neurobehavioural
      studies and molecular genetics has determined behavioural differences between the
      two species linked to the neural distribution of vasopressin 1A receptor in the
      male brain. More importantly, vasopressin 1A receptor gene transfer including the
      upstream regulatory sequence has enhanced male social affiliation in a non
      monogamous species. Male affiliative bonding depends upon release of both
      vasopressin and dopamine in the ventral striatum enhancing the reward value of
      odour cues that signal identity.

PMID- 15582384
TI  - Human altruism: economic, neural, and evolutionary perspectives.
AB  - Human cooperation represents a spectacular outlier in the animal world. Unlike
      other creatures, humans frequently cooperate with genetically unrelated
      strangers, often in large groups, with people they will never meet again, and
      when reputation gains are small or absent. Experimental evidence and evolutionary
      models suggest that strong reciprocity, the behavioral propensity for altruistic
      punishment and altruistic rewarding, is of key importance for human cooperation.
      Here, we review both evidence documenting altruistic punishment and altruistic
      cooperation and recent brain imaging studies that combine the powerful tools of
      behavioral game theory with neuroimaging techniques. These studies show that
      mutual cooperation and the punishment of defectors activate reward related neural
      circuits, suggesting that evolution has endowed humans with proximate mechanisms
      that render altruistic behavior psychologically rewarding.

PMID- 15582386
TI  - Electrical circuitry in biology: emerging principles from protein structure.
AB  - The rate of electron transfer by tunnelling decreases exponentially with
      distance, but is generally not rate limiting for distances up to 14A, enabling
      the robust design of redox systems. Fast transfer over distances greater than 14A
      is accomplished using diffusible electron carriers, an array of closely spaced
      redox centres or large-scale motion of a redox-active domain. Recent advances
      indicate that all three mechanisms are used in interprotein electron transfer.
      The classic stratagem, diffusible electron carriers, may be extended with either
      of the other designs. The use of an array of solvent-exposed, closely spaced
      redox centres can maximise productive collisions. Also, the use of conformational
      sampling via domain motion within the electron transfer complex optimises
      tunnelling probability.

PMID- 15582387
TI  - Structural bases of hydrogen tunneling in enzymes: progress and puzzles.
AB  - Accumulating experimental evidence suggests that the occurrence of hydrogen
      tunneling is likely to be widespread in enzyme-catalyzed reactions. The
      realization that hydrogen can transfer via tunneling mechanisms has far-reaching
      implications for our understanding of enzyme catalysis involving proton, hydride
      or hydrogen atom transfer reactions. The current status of the field is
      highlighted by three enzyme systems that have been under intensive study in
      recent years, including soybean lipoxygenase-1, thermophilic alcohol
      dehydrogenase and dihydrofolate reductase. Particular attention has been devoted
      to the issues of whether protein dynamics modulate hydrogen tunneling probability
      and whether the tunneling process contributes to the catalytic power of enzymes.

PMID- 15582388
TI  - Microspectrophotometry for structural enzymology.
AB  - For several decades, single-crystal microspectrophotometry has contributed to
      structural enzymology as a very useful complement to X-ray crystallography. In
      its most recent applications, it is the ideal tool to track chemistry as
      structure evolves in the course of time-resolved experiments, to identify freeze
      trapped catalytic intermediates and to assess radiation-induced effects on enzyme
      crystals. To these goals, instruments have been developed to record optical
      spectra 'on-line' in the course of X-ray data collection, whereas more rigorous
      polarized absorption studies 'off-line' play an essential role in describing what
      protein function is retained in the crystalline state and correlating it with the
      observed structures.

PMID- 15582389
TI  - Molecular mechanisms for multitasking: recent crystal structures of moonlighting
      proteins.
AB  - Recently determined X-ray crystal structures of moonlighting proteins are helping
      to elucidate how a protein can evolve two different functions and, in some cases,
      switch between its two functions in response to cellular conditions. X-ray
      crystal structures of the I-AniI homing endonuclease/maturase and the PutA
      proline dehydrogenase/transcription factor have provided evidence that these
      proteins utilize separate protein surfaces for their multiple functions. Also,
      the structure of the DegP (HtrA) protease/chaperone has revealed information
      about the mechanism of its chaperone activity and suggests how the protein
      regulates its protease activity. Comparing the structure of eta
      crystallin/retinal dehydrogenase with structures of its single-function enzyme
      homologs provides clues to changes in the protein structure that may have
      improved its ability to serve as a crystallin, but at the same time may have
      adversely affected its catalytic activity.

PMID- 15582390
TI  - The sema domain.
AB  - The sema domain was first defined from sequence by Kolodkin and colleagues in the
      early 1990s, and constitutes the distinctive structural and functional element of
      semaphorins, their plexin receptors and the receptor tyrosine kinases MET and
      RON, three protein families with major roles in development, tissue regeneration
      and cancer. Recently determined crystal structures of two semaphorins (SEMA3A and
      SEMA4D) and the MET receptor have shown that the sema domain consists of a highly
      conserved variant form of the seven-blade beta-propeller fold. The structures,
      however, also suggest differences between these families with respect to the mode
      of dimerisation and the regions of the domain involved in ligand-receptor
      interactions. This reflects the considerable plasticity and adaptation of the
      sema domain in order to meet different binding requirements, properties that may
      underlie the vast array of ligand-receptor specificities and functions of the
      semaphorin superfamily.

PMID- 15582391
TI  - The role of cysteine residues as redox-sensitive regulatory switches.
AB  - Redox-sensitive cysteine residues sense and transduce changes in cellular redox
      status caused by the generation of reactive oxygen species and the presence of
      oxidised thiols. Oxidation of such cysteines is converted into signals that
      control cell regulatory pathways and induction of gene expression. A variety of
      proteins, including transcription factors, molecular chaperones and protein
      tyrosine phosphatases, are regulated via redox processes. Common mechanisms
      underlie the sensitivity of cysteines to redox, such as proximity to polar and
      charged groups, and signal transduction is exerted via conformational changes
      that are conferred by the formation of disulfide and cyclic sulfenamide covalent
      bonds, and sulfenic and sulfonic acids.

PMID- 15582393
TI  - Rewiring cell signaling: the logic and plasticity of eukaryotic protein
      circuitry.
AB  - Living cells rival computers in their ability to process external information and
      make complex behavioral decisions. Many of these decisions are made by networks
      of interacting signaling proteins. Ongoing structural, biochemical and cell-based
      studies have begun to reveal several common principles by which protein
      components are used to specifically transmit and process information. Recent
      engineering studies demonstrate that these relatively simple principles can be
      used to rewire signaling behavior in a process that mimics the evolution of new
      phenotypic responses.

PMID- 15582394
TI  - Novel protein kinases and molecular mechanisms of autoinhibition.
AB  - During the past year, crystal structures of the PDK-1, ITK, Aurora-A, c-KIT and
      FLT-3 protein kinases in complex with several ATP-competitive inhibitors have
      been determined. Some structures have crystallized in catalytically active
      conformations, whereas others appear to be in inactive or native conformations.
      The differences between these two classes of structures provide further
      understanding of how kinase activity may be self-regulated in the cellular
      environment and how phosphorylation can modulate signalling at a molecular level.
      All of these structures provide a basis for designing selective protein kinase
      inhibitors of use in the treatment of cancer and autoimmune disease.

PMID- 15582395
TI  - Searching for new allosteric sites in enzymes.
AB  - The discovery of new allosteric sites generates opportunities for the
      identification of novel pharmaceuticals and increases our understanding of basic
      biological processes. Increasingly, allosteric sites are being discovered in
      various families of proteins by several methods, paving the way for the
      development of entirely new classes of drugs with a wide range of chemotypes. New
      allosteric sites in enzymes have been discovered both incidentally and by
      directed means, and the mechanisms by which allosteric activation and inhibition
      occur at these sites have been investigated. By exploring recent structurally
      well-characterized examples, trends begin to emerge for both the modes of binding
      and mechanisms of inhibition.

PMID- 15582396
TI  - Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1
      reverse transcriptases.
AB  - HIV undergoes rapid genetic variation; this variation is caused primarily by the
      enormous number of viruses produced daily in an infected individual. Because of
      this variation, HIV presents a moving target for drug and vaccine development.
      The variation within individuals has led to the generation of diverse HIV-1
      subtypes, which further complicates the development of effective drugs and
      vaccines. In general, it is more difficult to hit a moving target than a
      stationary target. Two broad strategies for hitting a moving target (in this
      case, HIV replication) are to understand the movement and to aim at the portions
      that move the least. In the case of anti-HIV drug development, the first option
      can be addressed by understanding the mechanism(s) of drug resistance and
      developing drugs that effectively inhibit mutant viruses. The second can be
      addressed by designing drugs that interact with portions of the viral machinery
      that are evolutionarily conserved, such as enzyme active sites.

PMID- 15582397
TI  - Structural insights into bacterial modulation of the host cytoskeleton.
AB  - Many bacterial pathogens manipulate the host cell cytoskeleton during infection.
      Such cytoskeletal modulation can occur at several points of contact between the
      pathogen and the host, and involves extracellular receptors, intracellular signal
      transduction and cytoskeletal proteins themselves. The field of bacterial
      pathogenesis has progressed dramatically over the past decade, such that
      structural knowledge is both timely and essential for a full appreciation of the
      biology at the pathogen-host interface. Several recent examples involving
      bacterial proteins that target actin, Rho family GTPases and extracellular
      receptors have contributed to a structural understanding of eukaryotic
      cytoskeletal modulation by pathogens.

PMID- 15582398
TI  - Three's company: component structures bring a closer view of tripartite drug
      efflux pumps.
AB  - Bacterial multidrug resistance is a serious clinical problem and is commonly
      conferred by tripartite efflux 'pumps' in the prokaryotic cell envelope. Crystal
      structures of the three components of a drug efflux pump have now been solved:
      the outer membrane TolC exit duct in the year 2000, the inner membrane AcrB
      antiporter in 2002 and the periplasmic adaptor MexA in 2004. These structures
      have enhanced our understanding of the principles underlying pump assembly and
      operation, and present pumps as new drug targets.

PMID- 15582399
TI  - Structural aspects of non-ribosomal peptide biosynthesis.
AB  - Small peptides have powerful biological activities ranging from antibiotic to
      immune suppression. These peptides are synthesized by non-ribosomal peptide
      synthetases (NRPS). Structural understanding of NRPS took a huge leap forward in
      2002; this information has led to several detailed biochemical studies and
      further structural studies. NRPS are complex molecular machines composed of
      multiple modules and each module contains several autonomously folded catalytic
      domains. Structural studies have largely focused on individual domains, isolated
      from the context of the multienzyme. Biochemical studies have looked at
      individual domains, isolated whole modules and intact NRPS, and the combined data
      begin to allow us to visualize the process of peptide assembly by NRPS.

PMID- 15582400
TI  - The polynucleotide ligase and RNA capping enzyme superfamily of covalent
      nucleotidyltransferases.
AB  - ATP- and NAD(+)-dependent DNA ligases, ATP-dependent RNA ligases and GTP
      dependent mRNA capping enzymes comprise a superfamily of proteins that catalyze
      nucleotidyl transfer to polynucleotide 5' ends via covalent enzyme-(lysyl-N)-NMP
      intermediates. The superfamily is defined by five peptide motifs that line the
      nucleotide-binding pocket and contribute amino acid sidechains essential for
      catalysis. Early crystal structures revealed a shared core tertiary structure for
      DNA ligases and capping enzymes, which are composed minimally of a
      nucleotidyltransferase domain fused to a distal OB-fold domain. Recent structures
      of viral and bacterial DNA ligases, and a fungal mRNA capping enzyme underscore
      how the substrate-binding and chemical steps of the ligation and capping pathways
      are coordinated with large rearrangements of the component protein domains and
      with remodeling of the atomic contacts between the enzyme and the nucleotide at
      the active site. The first crystal structure of an RNA ligase suggests that
      contemporary DNA ligases, RNA ligases and RNA capping enzymes evolved by fusion
      of ancillary effector domains to an ancestral catalytic module involved in RNA
      repair.

PMID- 15582401
TI  - Structural insights into protein-metal ion partnerships.
AB  - New metalloprotein structures continue to provide discoveries regarding protein
      metal ion partnerships. Many recent structures reveal metal ion sites that
      control or are controlled by protein conformational change, including modulation
      by alternative splice variants and striking conformational changes. Only a few
      novel catalytic metal centers have been revealed recently, such as the surprising
      Ni-hook superoxide dismutase catalytic site and the cubane-like Mn(3)CaO(4)
      photosynthetic oxygen-evolving center. However, important new variations on old
      heme themes, breakthroughs in the fields of metal ion regulation and
      metallochaperones, and captivating insights into partnerships between proteins
      and minerals have also been described. Very high resolution metal site structures
      and metalloprotein design will be increasingly important in order to leverage the
      wealth of native metalloprotein structures into a deep understanding of metal ion
      site specificity and activity.

PMID- 15582402
TI  - Structure-based design of cycloamide-urethane-derived novel inhibitors of human
      brain memapsin 2 (beta-secretase).
AB  - A series of novel macrocyclic amide-urethanes was designed and synthesized based
      upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight
      residues) bound to memapsin 2. Ring size and substituent effects have been
      investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited
      low nanomolar inhibitory potencies against human brain memapsin 2 (beta
      secretase).

PMID- 15582403
TI  - A new strategy to combat Alzheimer's disease. Combining radical-scavenging
      potential with metal-protein-attenuating ability in one molecule.
AB  - Oxidative stress and excessive redox metals have been implicated in the
      pathogenesis of Alzheimer's disease (AD), which leads to the tentative employment
      of radical scavengers and metal chelators in clinical therapy of AD. The
      preliminary successes of both therapy strategies inspire us to propose that
      better clinical effects can be expected for a compound combining radical
      scavenging potential with metal-protein-attenuating ability. Based on theoretical
      investigation, we indicate that two novel metal chelators (1-(benzimidazole-2
      ylmethyl)-1,4,7-triazacyclononane and 1,4-bis(benzimidazole-2-ylmethyl)-1,4,7
      triazacyclonone), especially the latter, are promising to fulfill this new
      strategy.

PMID- 15582404
TI  - Modulators of the human CCR5 receptor. Part 1: Discovery and initial SAR of 1
      (3,3-diphenylpropyl)-piperidinyl amides and ureas.
AB  - Investigation of weak screening hits led to the identification of N-alkyl-N-[1
      (3,3-diphenylpropyl)piperidin-4-yl]-2-phenylacetamides and N-alkyl-N-[1-(3,3
      diphenylpropyl)piperidin-4-yl]-N'-benzylureas as potent, selective ligands for
      the human CCR5 chemokine receptor.

PMID- 15582405
TI  - 5-Amidinobenzo[b]thiophenes as dual inhibitors of factors IXa and Xa.
AB  - Syntheses and SAR studies of 5-amidinobenzo[b]thiophene analogs provided
      compounds with low submicromolar factor IXa activity and equal or slightly better
      selectivity relative to factor Xa.

PMID- 15582406
TI  - Anti-coxsackievirus B3 activity of 2-amino-3-nitropyrazolo[1,5-a]pyrimidines and
      their analogs.
AB  - A novel class of 2-amino-4-nitropyrazolo[1,5-a]pyrimidines has been identified as
      potent inhibitors of coxsackievirus B3 replication. The synthesis of these
      compounds is based on the regioselective reaction of 3,5-diamino-5-nitropyrazole
      with unsymmetrical beta-diketones at catalysis by hydrochloric acid leading to 2
      amino-4-nitropyrazolo[1,5-a]pyrimidines as key steps.

PMID- 15582407
TI  - Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral
      active VLA-4 antagonist.
AB  - An investigation into the structure-activity relationship of a lead compound,
      prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4
      piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid
      derivatives as potent VLA-4 antagonists with low nanomolar IC(50) values. A
      representative compound morpholinyl-4-piperidinylacetic acid derivative (13d:
      IC(50)=4.4 nM) showed efficacy in the Ascaris-antigen sensitized murine airway
      inflammation model by oral administration.

PMID- 15582408
TI  - Syntheses of 2,4,6-trisubstituted pyrimidine derivatives as a new class of
      antifilarial topoisomerase II inhibitors.
AB  - A series of 21 compounds of trisubstituted pyrimidine derivatives have been
      synthesized and evaluated for their in vitro topoisomerase II inhibitory activity
      against filarial parasite Setaria cervi. Out of these, seven compounds (8, 11-14,
      25 and 28) have shown 60-80% inhibition at 40 and 20 microg/mL concentration.
      Five compounds (12, 13, 14, 25 and 28) exhibited 70-80% inhibition at 10
      microg/mL concentration and three compounds (13, 14 and 28) have shown 40-60%
      inhibition at 5 microg/mL concentration. All the above mentioned compounds have
      shown better topo II inhibitory activity than standard antifilarial drug (DEC)
      and enzyme topo II inhibitors (Novobiocin, Nalidixic acid).

PMID- 15582409
TI  - 2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the
      incorporation of phenoxy substituents.
AB  - Herein we describe a series of potent and selective PPARgamma agonists with
      moderate PPARalpha affinity and little to no affinity for other nuclear
      receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these
      compounds are efficacious at low doses in glucose normalization and plasma
      triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies
      to be advanced to clinical evaluation for the treatment of type II diabetes.

PMID- 15582410
TI  - 2,3-Ethylene- and 2,3-trimethylene-bridged analogues of the group III
      metabotropic glutamate receptor ligand 2-amino-4-phosphonobutanoic acid.
AB  - The racemic trans- and cis-isomers of 1-amino-2-phosphonomethyl
      cyclobutanecarboxylic acid (5 and 6) and 1-amino-2-phosphonomethyl
      cyclopentanecarboxylic acid (7 and 8) were synthesized as extensions of the
      mGluR4 agonists trans- and cis-1-amino-2-phosphonomethyl-cyclopropanecarboxylic
      acid (3 and 4). Although the methylene bridge in 3 and 4 allows for retention of
      affinity toward the mGluR4 receptor, increasing the bridging unit to the ethylene
      group as in 5 and 6 or to the trimethylene group as in 7 and 8 introduces
      sufficient steric hindrance to eliminate affinity for the mGluR4 receptor.

PMID- 15582411
TI  - Synthesis of the naphthalene-derived inhibitors against Cdc25A dual-specificity
      protein phosphatase and their biological activity.
AB  - The novel naphthalene-type analogues 14 and 18 and the naphthoquinone-type
      analogues, 8, 9, 15, 16, 19, 21, 22, and 23-28 have been synthesized, and their
      in vitro Cdc25A phosphatase-inhibitory activity was examined. In assessment of
      the inhibitory activity, it was revealed that the naphthoquinone core is
      contributed to the activity, rather than the alkyl side chain.

PMID- 15582412
TI  - Possible role of hydroxyl radicals in the oxidative degradation of folic acid.
AB  - Hydroxyl radicals have been found to cause oxidative N-dealkylation of amines
      including folic acid via a hydrogen atom transfer mechanism.

PMID- 15582413
TI  - Design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8
      chloropyrimido-[4,5-b]quinolines as novel antimalarials.
AB  - Novel 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines were
      designed based on a pharmacophore developed for potent antimalarial activity
      using Chem-X and MOE softwares. The designed molecules were synthesized by
      following a novel route and were evaluated by Rane's test for blood
      schizonticidal activity in mice infected by Plasmodium berghei. Based on the Mean
      Survival Time (MST) data, of the nine compounds evaluated, three had curative
      potential when compared with chloroquine.

PMID- 15582414
TI  - A new synthetic analogue of thymidine, 7-(3-bromo-phenoxy)-thymidine, inhibits
      the proliferation of tumor cells.
AB  - Modified thymidine analogues have been highlighted as useful agents for the
      treatment of cancer and viral diseases due to their potent biological activities.
      In the present study, we synthesized a new thymidine analogue, 7-(3-bromo
      phenoxy)-thymidine (4a), as a potential lead for anti-tumor agent. Compound 4a
      potently inhibits HeLa cell proliferation with an IC(50) of 15 microM.

PMID- 15582415
TI  - Optimization of pyrrolidinone based HIV protease inhibitors.
AB  - Optimization of P1-substituted pyrrolidinone based HIV protease inhibitors has
      yielded analogs with very potent antiviral activity.

PMID- 15582416
TI  - Synthesis and biological evaluation of novel steroidal pyrazoles as substrates
      for bile acid transporters.
AB  - A series of novel steroidal pyrazoles was synthesized as substrates for bile acid
      transporters to explore their potential as drug carriers. The selected pyrazole
      fused bile acids were further conjugated with drugs and drug surrogates. Their in
      vitro transport activities were evaluated in human ileal bile acid transporter
      (hIBAT) and human liver bile acid transporter (hLBAT) expressing Chinese hamster
      ovary (CHO)-cells and Xenopus laevis oocytes. The results of synthetic efforts
      and transporter assays studies are described herein.

PMID- 15582417
TI  - Characterization of L-glutamine:2-deoxy-scyllo-inosose aminotransferase (tbmB)
      from Streptomyces tenebrarius.
AB  - 2-Deoxystreptamine (DOS)-containing aminoglycoside-aminocyclitol (AmAc)
      antibiotics represent the majority of clinically important AmAcs. Biosynthetic
      investigations of formation of DOS in actinomycetes are limited to the
      characterization of 2-deoxy-scyllo-inosose synthase, the first step enzyme of the
      DOS biosynthetic pathway. A gene encoding L-glutamine:2-deoxy-scyllo-inosose
      aminotransferase (tbmB) from the tobramycin producer Streptomyces tenebrarius was
      expressed heterologously in Escherichia coli. The conversions of 2-deoxy-scyllo
      inosose to 2-deoxy-scyllo-inosamine and scyllo-inosose to scyllo-inosamine with
      the activity of TbmB were determined in vitro. The results indicate that tbmB
      catalyzes the second step of the DOS biosynthetic pathway during the biosynthesis
      of 2-deoxystreptamine, a subunit of tobramycin, in S. tenebrarius.

PMID- 15582418
TI  - Naphthamidine urokinase plasminogen activator inhibitors with improved
      pharmacokinetic properties.
AB  - A series of non-amide-linked 6-substituted-2-naphthamidine urokinase plasminogen
      activator (uPA) inhibitors are described. These compounds possess excellent
      binding activities and selectivities with significantly improved pharmacokinetic
      profiles versus previously described amide-linked inhibitors.

PMID- 15582419
TI  - Amide derivatives of 9,11-seco-estra-1,3,5(10)-trien-11-oic acid as modified
      orally active estrogen agonists with moderate antagonistic activity.
AB  - Synthesis of amide derivatives of 9,11-seco-estra-1,3,5(10)-trien-11-oic acid
      containing alkyl and aromatic amine residues has been carried out with an aim to
      prepare orally active estrogen antagonists. Modification of the estradiol
      molecule in the form of C-seco-amide derivatives has led to their high oral
      absorption. Compounds 7 an n-propyl amide, 8 an n-butyl amide, and 16 a p
      anisidyl amide of C-seco-estrane showed significant estrogen antagonistic
      activity (>20%), while, the majority of compounds possessed high estrogen
      agonistic activity on oral administration at 10mg/kg dose in rats.

PMID- 15582420
TI  - Heterocyclic sulfoxide and sulfone inhibitors of fatty acid amide hydrolase.
AB  - A novel series of heterocyclic sulfoxides and sulfones was prepared and examined
      as potential inhibitors of fatty acid amide hydrolase (FAAH), the enzyme
      responsible for inactivation of neuromodulating fatty acid amides including
      anandamide and oleamide.

PMID- 15582421
TI  - Estrogen receptor ligands. Part 9: Dihydrobenzoxathiin SERAMs with alkyl
      substituted pyrrolidine side chains and linkers.
AB  - A series of dihydrobenzoxathiin SERAMs with alkylated pyrrolidine side chains or
      alkylated linkers was prepared. Minor modifications in the side chain or linker
      resulted in significant effects on biological activity, especially in uterine
      tissue.

PMID- 15582422
TI  - Aminothiazole inhibitors of HCV RNA polymerase.
AB  - Aminothiazole-based inhibitors designed for HCV polymerase display low micromolar
      potencies in biochemical assays. These compounds show a stringent preference for
      a cyclohexyl hydrophobe at the 2-amino position. The composition of these
      compounds suggests that they may be interacting at a recently discovered
      allosteric site on the polymerase.

PMID- 15582423
TI  - Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain.
AB  - Herein we report the synthesis and evaluation of a series of thiosemicarbazones
      as potential inhibitors of cysteine proteases relevant to parasitic diseases.
      Derivatives of thiosemicarbazone 1 were discovered to be potent inhibitors of
      cruzain and rhodesain, crucial proteases in the life cycles of Trypanosoma cruzi
      and T. brucei rhodesiense, the organisms causing Chagas' disease and sleeping
      sickness. However, the entire series had only modest potency against falcipain-2,
      an essential protease for Plasmodium falciparum, the organism causing malaria.
      Among the active inhibitors, several potently inhibited proliferation of cultures
      of T. brucei. However, only modest activity was observed in inhibition of
      proliferation of T. cruzi or P. falciparum.

PMID- 15582424
TI  - Design, synthesis, and structural analysis of inhibitors of influenza
      neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid
      core.
AB  - (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3
      methoxycarbonyl]tetrahydrofuran-5-carboxylic acid (9) and (+/-)-(2R,3R,5R)-[2-(1'
      S-acetamido-3'-methyl)butyl-3-(4'-imidazolyl)]tetrahydrofuran 5-carboxylic acid
      (14) were synthesized as inhibitors of influenza neuraminidase (NA). Both
      compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and
      NA B with an IC(50) of 1.0 microM.

PMID- 15582425
TI  - A comparative binding study of BIV Tat peptide against its TAR RNA duplex, RNA
      DNA heteroduplex and DNA duplex.
AB  - Association between RNA and DNA strands to form RNA-DNA heteroduplex is important
      in many biological processes such as transcription, DNA replication and reverse
      transcription. Herein, binding affinities of a 17-mer BIV Tat peptide is compared
      with TAR DNA duplex, TAR RNA-DNA heteroduplex and TAR RNA duplex. It was observed
      that binding affinities of Tat peptide is comparable against DNA-RNA heteroduplex
      and RNA duplex, whereas DNA duplex binding is decidedly poor.

PMID- 15582426
TI  - New 2-bromomethyl-8-substituted-benzo[c]chromen-6-ones. Synthesis and biological
      properties.
AB  - New 2-bromomethyl-8-substituted-benzo[c]chromen-6-ones have been synthesized and
      their bioactive properties have been evaluated on different enzymatic models:
      serine proteases (trypsin and alpha-chymotrypsin), HIV aspartyl protease, nitric
      oxide synthase and a panel of protein kinases. These new derivatives can provide
      upon chemical or enzymatic attack, very reactive quinonimine methide
      intermediates, which could be utilized for the design of enzyme inhibitors. We
      found that some of these new derivatives exhibit modest inhibitory activities on
      the studied enzyme models, but it could be improved after structure optimization.

PMID- 15582427
TI  - Enzymatic syntheses and selective hydrolysis of O-beta-D-galactopyranosides using
      a marine mollusc beta-galactosidase.
AB  - The use of crude extract of the hepatopancreas of Aplysia fasciata, a large
      mollusc belonging to the order Anaspidea containing a beta-galactosidase
      activity, was reported for the synthesis of different galactosides. Good yields
      with polar acceptors and the uncommon beta-1-3 selectivity in the
      transgalactosylation reactions with most of the acceptors were observed. A beta-1
      2 selectivity in the hydrolytic conditions was also observed and discussed.

PMID- 15582428
TI  - Synthesis and activity of 8-substituted benzo[c]quinolizin-3-ones as dual
      inhibitors of human 5alpha-reductases 1 and 2.
AB  - Some potent dual inhibitors of 5alpha-reductases 1 and 2, based on the
      benzo[c]quinolizin-3-one structure and with IC(50) values ranging between 93 and
      166nM for both isozymes, were found. The presence of the F atom on the ester
      moiety at the position 8 was crucial. This result can help in the design of other
      potent, dual inhibitors to be developed as drugs in the treatment of 5alpha
      reductase related diseases.

PMID- 15582429
TI  - 5'-Homoaristeromycin. Synthesis and antiviral activity against orthopox viruses.
AB  - An efficient synthesis of 5'-homoaristeromycin has been developed. This permitted
      an extensive antiviral analysis, which found potent activity toward vaccinia,
      cowpox, and monkeypox viruses. For comparative purposes, 5'-homoadenosine was
      made available by a newly designed route and found to be inactive.

PMID- 15582430
TI  - Design and synthesis of o-trifluoromethylbiphenyl substituted 2-amino
      nicotinonitriles as inhibitors of farnesyltransferase.
AB  - A non-methionine FT inhibitor lead structure (1) was designed through computer
      modeling of the peptidomimetic FT inhibitor ABT839. Optimization of this lead
      resulted in compounds 2e and 2g, with FT IC(50) values of 1.3 and 1.8 nM, GGT
      IC(50) of 1400 nM, and EC(50) (Ras processing) values of 13 and 11 nM,
      respectively.

PMID- 15582431
TI  - Synthesis of digalactosyl diacylglycerols and their structure-inhibitory activity
      on human lanosterol synthase.
AB  - Digalactosyl and monogalactocyl diacylglycerols (DGDG and MGDG), which were
      identified as anti-hyperlipemia active components in Colocasia esculenta (Taro),
      were synthesized. The inhibitory activity of DGDG, MGDG and related compounds on
      human lanosterol synthase was evaluated as anti-hyperlipemic activity. DGDG with
      two myristoyl groups at both sn-1 and sn-2 positions and with an oleoyl group at
      the sn-1 position showed the most potent activity.

PMID- 15582432
TI  - Cytotoxic neolignans: an SAR study.
AB  - The neolignans, magnolol 1 and honokiol 2 have been reported to inhibit the
      growth of several tumor cell lines in vitro and in vivo. The chemical structure
      of magnolol and honokiol consists of biphenyl skeleton with phenolic and allylic
      functionalities. Analogs of 1 and 2 containing different substitution have been
      studies for their effect on the growth of Hep-G2 and their structure-activity
      relationships were reported in this work.

PMID- 15582433
TI  - Efficient cleavage of RNA, enhanced cellular uptake, and controlled intracellular
      localization of conjugate DNAzymes.
AB  - Conjugate DNAzymes with polyamines and peptides were successfully prepared by
      solid phase fragment condensation (SPFC) and showed up to 4.2 times higher
      catalytic efficiency (k(cat)/K(m)) and enhanced tolerance against DNase
      1digestion. To be pointed out, intracellular localization of DNAzymes could be
      controlled by conjugated with naturally occurring signal peptides responsible for
      nuclear cytoplasmic transport of proteins.

PMID- 15582434
TI  - Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]
      1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2
      piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4
      receptor agonist.
AB  - We report the discovery and optimization of substituted 2-piperazinecarboxamides
      as potent and selective agonists of the melanocortin subtype-4 receptor. Further
      in vivo development of lead agonist, MB243, is disclosed.

PMID- 15582435
TI  - Design, synthesis, and biological evaluation of achiral analogs of duocarmycin
      SA.
AB  - The design, synthesis, as well as biochemical and biological evaluation of two
      novel achiral analogs of duocarmycin SA (DUMSA), 1 and 2, are described. Like CC
      1065 and adozelesin, compounds 1 and 2 covalently reacted with adenine-N3 in AT
      rich sequences and led to the formation of DNA strand breaks upon heating. The
      cytotoxicity of compounds 1 and 2 against human cancer cells (K562, LS174T) was
      determined using a MTT assay giving IC(50) values in the low nanomolar. Further
      cytotoxicity screening of compound 2 conducted by the NCI against a panel of 60
      different human cancer cell lines indicated that it was particularly active
      against several solid tumor cells lines derived from the lung, colon, CNS, skin,
      and breast.

PMID- 15582436
TI  - N-hydroxy-2-(naphthalene-2-ylsulfanyl)-acetamide, a novel hydroxamic acid-based
      inhibitor of aminopeptidase N and its anti-angiogenic activity.
AB  - In the course of our screening, N-hydroxy-2-(naphthalene-2-ylsulfanyl)-acetamide
      (1), which contains a metal-chelating hydroxamate group, has been identified as a
      potent inhibitor of aminopeptidase N (APN, EC 3.4.11.2). Compound 1 potently
      inhibited APN activity with a K(i) value of 3.5 microM. It also inhibited the
      basic fibroblast growth-factor-induced invasion of bovine aortic endothelial
      cells at low micromolar concentrations.

PMID- 15582437
TI  - Discovery of novel tetrahydroisoquinoline derivatives as potent and selective
      factor Xa inhibitors.
AB  - A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were
      designed and synthesized. Among these derivatives, compounds 1 and 2 (JTV-803)
      exhibited potent inhibitory activity against FXa and good selectivity with
      respect to other serine proteases (thrombin, plasmin, and trypsin). In addition,
      compound 2 exhibited potent anti-FXa activity after intravenous and oral
      administration to cynomolgus monkey, and showed a dose-dependent antithrombotic
      effect in a rat model of venous thrombosis.

PMID- 15582438
TI  - Himeic acid A: a new ubiquitin-activating enzyme inhibitor isolated from a marine
      derived fungus, Aspergillus sp.
AB  - A new ubiquitin-activating enzyme (E1) inhibitor, himeic acid A, was isolated
      from a culture of marine-derived fungus, Aspergillus sp. The structure was
      determined by spectroscopic analysis. The formation of an E1-ubiquitin (Ub)
      intermediate was 65% inhibited by himeic acid A at the concentration of 50
      microM, while two new related compounds, himeic acids B and C, showed little
      inhibitory activity even at 100 microM.

PMID- 15582439
TI  - Amino-substituted heterocycles as isosteres of trans-cinnamides: design and
      synthesis of heterocyclic biaryl sulfides as potent antagonists of LFA-1/ICAM-1
      binding.
AB  - 2-Amino-4-phenyl pyridine and, to a lesser extent, 4-amino-6-phenyl pyrimidine,
      were established as isosteres of trans-cinnamide moiety. Applying this isosterism
      to previously reported p-arylthio cinnamides resulted in the identification of 4
      amino-6-(p-arylthio)phenyl-pyrimidines and 2-amino-4-(p-arylthio)phenyl-pyridines
      as potent antagonists of LFA-1/ICAM-1 binding.

PMID- 15582440
TI  - QSAR study on pK(a) vis-a-vis physiological activity of sulfonamides: a
      dominating role of surface tension (inverse steric parameter).
AB  - The paper describes the dominating role of surface tension (ST) on the modeling,
      monitoring, and estimating pK(a) for a large series of 43 substituted
      sulfonamides. Because of the direct correlation of ST with parachor (Pc) vis-a
      vis molecular volume (MV), ST is considered as a steric parameter. Single as well
      as multi-parametric regressions have indicated that ST has a dominating role in
      QSAR of the set of sulfonamides used and that excellent results are obtained in
      multi-parametric regression analysis. The results are discussed critically on the
      basis of statistical parameters.

PMID- 15582441
TI  - Design and synthesis of highly active Alzheimer's beta-secretase (BACE1)
      inhibitors, KMI-420 and KMI-429, with enhanced chemical stability.
AB  - Recently, we reported potent and small-sized BACE1 inhibitors KMI-358 and KMI-370
      in which the Glu residue is replaced by a beta-N-oxalyl-DAP (l-alpha,beta
      diaminopropionyl) residue at the P(4) position. The beta-N-oxalyl-DAP group is
      important for enhancing BACE1 inhibitory activity, but these inhibitors
      isomerized to alpha-N-oxalyl-DAP derivatives in solvents. Hence, we used a
      tetrazole moiety as a bioisostere of the free carboxylic acid of the oxalyl
      group. KMI-420 and KMI-429, containing a tetrazole ring, showed improved
      stability and potent enzyme inhibitory activity.

PMID- 15582442
TI  - 2,3-Diphenylpropionic acids as potent VLA-4 antagonists.
AB  - The discovery and SAR of 2,3-diphenylpropionic acid derivatives as highly potent
      VLA-4 antagonists are described. One representative compound, 9cc has inhibited
      intercellular adhesion by a VCAM-1/VLA-4 interaction with an IC(50) of 1.7 nM,
      and has good pharmacokinetics and oral bioavailability.

PMID- 15582443
TI  - Synthesis and in vitro study of novel Mannich bases as antibacterial agents.
AB  - A series of novel Mannich bases derived from 5-chloro-2-methoxybenzamide and
      sulfonamides/amines have been synthesised and the antibacterial activities were
      evaluated against various Gram positive and Gram negative strains of bacteria.
      Some of the synthesized compounds showed superior in vitro activities as compared
      to their parent sulfonamides.

PMID- 15582444
TI  - A new class of androgen receptor antagonists bearing carborane in place of a
      steroidal skeleton.
AB  - A new class of androgen receptor antagonists containing dicarba-closo
      dodecaborane (carborane) as a hydrophobic skeletal structure is described. The
      designed molecules bear the characteristic polar components of endogenous
      agonists, but have a hydrophobic carborane cage instead of the steroidal
      skeleton. These compounds bind to androgen receptor and show anti-androgenic
      activity towards androgen-dependent SC-3 cells with almost the same potency as
      the known anti-androgen hydroxyflutamide.

PMID- 15582445
TI  - Novel 1beta-methylcarbapenems with isoxazoloethenyl moieties containing
      carboxylic acid sodium salt.
AB  - The synthesis of novel 1beta-methylcarbapenems 1a,b having sodium 5-(3- and 5
      carboxylic acid)isoxazoloethenyl moieties at C-5 position of pyrrolidine ring and
      their biological evaluation are described. Both compounds showed potent and well
      balanced antibacterial activity as well as high stability to DHP-I. The selected
      sodium 3-carboxylic acid derivative 1a possessed excellent DHP-I stability and
      advanced pharmacokinetic parameters in comparison with 2 and meropenem.

PMID- 15582446
TI  - Antitumor agents. Part 236: Synthesis of water-soluble colchicine derivatives.
AB  - Water-soluble colchicine derivatives were synthesized from 2-demethylcolchicine
      and 2-demethylthiocolchicine and evaluated in vitro against human tumor cell
      replication and for inhibition of tubulin polymerization. The glycinate esters
      (4, 5) and their tartaric acid salts (4a, 5a) showed potent cytotoxic activity in
      three different tumor cell lines with IC(50) values ranging from 0.02 to 0.88
      microg/mL. The thiocolchicine analogs (5, 5a) were more potent than the
      colchicine analogs (4, 4a) in the tubulin polymerization assay. In particular,
      the water-soluble salt 5a merits preclinical development as an antitumor agent.

PMID- 15582447
TI  - beta-Peptides as inhibitors of protein-protein interactions.
AB  - We became interested several years ago in exploring whether 14-helical beta
      peptide foldamers could bind protein surfaces and inhibit protein-protein
      interactions, and if so, whether their affinities and specificities would compare
      favorably with those of natural or miniature proteins. This exploration was
      complicated initially by the absence of a suitable beta-peptide scaffold, one
      that possessed a well-defined 14-helical structure in water and tolerated the
      diverse sequence variation required to generate high-affinity protein surface
      ligands. In this perspective, we describe our approach to the design of adaptable
      beta-peptide scaffolds with high levels of 14-helix structure in water, track the
      subsequent development of 14-helical beta-peptide protein-protein interaction
      inhibitors, and examine the potential of this strategy for targeting other
      therapeutically important proteins.

PMID- 15582448
TI  - Natural and synthetic cage compounds incorporating the 2,9,10
      trioxatricyclo[4.3.1.03,8]decane type moiety.
AB  - The 2,9,10-trioxatricyclo[4.3.1.0(3,8)]decane moiety is a tetracyclic cage-like
      orthoester incorporated in the structure of a series of daphnane derivatives such
      as resiniferatoxin (RTX), kirkinine, synaptolepis factors, huratoxin etc.,
      exhibiting various biological activities. The approaches to the preparation of
      cage-like orthoesters starting from partially acylated or unmodified 1,2,4
      trihydroxycyclohexane moieties built onto natural as well as synthetic compounds
      are discussed. Orthoester derivatives of RTX analogs, Ceverathrum alkaloids,
      myoinositol and pyranoses are included. Stereochemical requirements to the
      formation of the orthoester unit are discussed. The biological activity of
      different compounds containing the cage-like orthoester structural fragment is
      given. The literature is reviewed till 2004.

PMID- 15582449
TI  - Pore formation in and enlargement of phospholipid liposomes by synthetic models
      of ceramides and sphingomyelin.
AB  - A family of compounds having twin octadecyl anchor chains and various polar
      headgroups were designed to be ceramide mimics. The compounds prepared increase
      the apparent permeability of phospholipid vesicles to chloride and
      carboxyfluorescein anions. In addition, significantly larger vesicles are
      observed after exposure to these compounds suggesting the possibility of
      vesicular fusion.

PMID- 15582450
TI  - Synthesis and photodynamic activity of zinc(II) phthalocyanine derivatives
      bearing methoxy and trifluoromethylbenzyloxy substituents in homogeneous and
      biological media.
AB  - Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or
      trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two
      step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence
      spectroscopic studies were analyzed in different media. These compounds are
      essentially non-aggregated in the organic solvent. Fluorescence quantum yields
      (phi(F)) of 0.26 for ZnPc 3 and 0.25 for ZnPc 4 were calculated in
      tetrahydrofuran (THF). The photodynamic activity of these compounds was compared
      in both THF containing photooxidizable substrates and in vitro on Hep-2 human
      larynx-carcinoma cell line. The production of singlet molecular oxygen,
      O(2)((1)Delta(g)), was determined using 9,10-dimethylanthracene yielding values
      of approximately 0.56 for both sensitizers. Under these conditions, the addition
      of beta-carotene (Car) suppresses the O(2)((1)Delta(g))-mediated photooxidation.
      In biological medium, no dark cytotoxicity was found for cells incubated with 0.1
      microM of phthalocyanines 3 and 4 for 24 h. However, under similar conditions 0.5
      microM of ZnPc 4 was toxic (70% cell survival). The uptake into Hep-2 cells was
      evaluated using 0.1muM of sensitizer, reaching values of approximately 0.05
      nmol/10(6) cells after 3h of incubation at 37 degrees C. The cell survival after
      irradiation of the cultures with visible light was dependent upon both light
      exposure level and intracellular sensitizer concentration. A higher
      photocytotoxic effect was found for ZnPc 3 with respect to 4 (32%/70% cell
      survival after 15 min of irradiation). Also, these studies were performed
      treating the cells with 0.5 microM of ZnPc 3. In this case, an increase in the
      uptake (approximately 0.28 nmol/10(6) cells) was observed, which is accompanied
      by a higher photocytotoxic activity (20% cell survival). These results show that
      even though both sensitizer present similar photophysical properties in
      homogeneous medium, the photodynamic behavior in cellular media can significantly
      be changed.

PMID- 15582451
TI  - Photocontrol of nitric oxide production in cell culture using a caged isoform
      selective inhibitor.
AB  - Over the past decade, multiphoton microscopy has progressed from a photonic
      novelty to a technique whose application is currently experiencing exponential
      growth in the biological sciences. A novel application of this technology with
      significant therapeutic potential is the control of drug activity by multiphoton
      photolysis of caged therapeutics. As an initial case study, the potent isoform
      selective inhibitor N-(3-(aminomethyl)benzyl) acetamidine (1400W) of inducible
      nitric oxide synthase (iNOS) has been conjugated to a caging molecule 6-bromo-7
      hydroxy-4-hydroxyquinoline-2-ylmethyl acetyl ester (Bhc). Here we present the
      first report of a bulk therapeutic effect, inhibition of nitric oxide production,
      in mammalian cell culture by multiphoton photolysis of a caged drug, Bhc-1400W.
      Mouse macrophage RAW 264.7 cells induced with bacterial lipopolysaccharides to
      express iNOS were used to assess the therapeutic value of the conjugated
      inhibitor. Both 1400W and Bhc-1400W are stable in metabolically active cells and
      an optimal time interval for the photorelease of the inhibitor was determined.
      The ratios of the IC(50) values of Bhc-1400W over 1400W calculated in the
      presence of iNOS enzyme and in RAW 264.7 cell culture are 19 and 100,
      respectively, indicating that a broad therapeutic range exists in cell culture.
      Multiphoton uncaging protocols and therapeutic doses of inhibitors were not
      cytotoxic. Photocontrol of LPS induced nitric oxide production was achieved in
      mammalian cell culture using a single laser focal volume. This technology has the
      potential to control active drug concentrations in vivo, a lack of which is one
      of the main problems currently associated with systemic drug administration.

PMID- 15582452
TI  - The discovery and preparation of disubstituted novel amino-aryl-piperidine-based
      renin inhibitors.
AB  - Recently, trans-disubstituted oxo-aryl-piperidines have been identified as small
      molecule nonpeptide renin inhibitors for the modulation of hypertension. Herein,
      we report on the discovery and preparation of a new class of novel cis
      disubstituted amino-aryl-piperidines as a mixture of enantiomers that are potent
      in vitro renin inhibitors and also, possess in vivo antihypertensive activity in
      a double transgenic mouse model.

PMID- 15582453
TI  - Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate
      analogs.
AB  - Three nonhydrolyzable aspartyl adenylate analogs have been prepared and tested as
      inhibitors of E. coli aspartyl-tRNA synthetase. 5'-O-[N-(L
      Aspartyl)sulfamoyl]adenosine is a potent competitive inhibitor (K(i) = 15 nM)
      whereas L-aspartol adenylate is a weaker inhibitor (K(i) = 45 microM) with
      respect to aspartic acid. The corresponding ketomethylphosphonate (a novel
      isosteric replacement) is also a strong inhibitor (K(i) = 123 nM).

PMID- 15582454
TI  - Synthesis and in vitro binding of N-phenyl piperazine analogs as potential
      dopamine D3 receptor ligands.
AB  - A series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine
      analogs were prepared and their affinities for dopamine D(2), D(3), and D(4)
      receptors were measured in vitro. Binding studies were also conducted to
      determine if the compounds bound to sigma (sigma(1) and sigma(2)) and serotonin
      (5-HT(1A), 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(3), 5-HT(4), 5-HT(5), 5-HT(6), and
      5-HT(7)) receptors. The results of the current study revealed a number of
      compounds (12b, 12c, 12e, and 12g) having a high affinity for D(3) (K(i) at D(3)
      receptors ranging from 0.3 to 0.9 nM) versus D(2) (K(i) at D(2) receptors ranging
      from 40 to 53 nM) receptors and a log P value indicating that they should readily
      cross the blood brain barrier (log P = 2.6-3.5). All of the compounds evaluated
      in this study had a high affinity for serotonin 5-HT(1A) receptors. These
      compounds may be useful as probes for studying the behavioral pharmacology of the
      dopamine D(3) receptor, as well as lead compounds for the development of
      radiotracers for studying D(3) receptor regulation in vivo with the functional
      imaging technique, positron emission tomography.

PMID- 15582455
TI  - Structure-activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the
      cannabinoid CB(1) and CB(2) receptors: steric and electronic effects of naphthoyl
      substituents. New highly selective CB(2) receptor agonists.
AB  - In an effort to improve indole-based CB(2) cannabinoid receptor ligands and also
      to develop SAR for both the CB(1) and CB(2) receptors, 47 indole derivatives were
      prepared and their CB(1) and CB(2) receptor affinities were determined. The
      indole derivatives include 1-propyl- and 1-pentyl-3-(1-naphthoyl)indoles both
      with and without a 2-methyl substituent. Naphthoyl substituents include 4- and 7
      alkyl groups as well as 2-, 4-, 6-, 7-methoxy and 4-ethoxy groups. The effects of
      these substituents on receptor affinities are discussed and structure-activity
      relationships are presented. In the course of this work three new highly
      selective CB(2) receptor agonists were identified, 1-propyl-3-(4-methyl-1
      naphthoylindole (JWH-120), 1-propyl-2-methyl-3-(6-methoxy-1-naphthoylindole (JWH
      151), and 1-pentyl-3-(2-methoxy-1-naphthoylindole (JWH-267). GTPgammaS assays
      indicated that JWH-151 is a full agonist at CB(2), while JWH-120 and JWH-267 are
      partial agonists. Molecular modeling and receptor docking studies were carried
      out on a set of 3-(4-propyl-1-naphthoyl)indoles, a set of 3-(6-methoxy-1
      naphthoyl)indoles and the pair of N-pentyl-3-(2-methoxy-1-naphthoyl)indoles.
      Docking studies indicated that the CB(1) receptor affinities of these compounds
      were consistent with their aromatic stacking interactions in the aromatic
      microdomain of the CB(1) receptor.

PMID- 15582456
TI  - Boronic acid fluorescent sensors for monosaccharide signaling based on the 6
      methoxyquinolinium heterocyclic nucleus: progress toward noninvasive and
      continuous glucose monitoring.
AB  - The synthesis, characterization, and spectral properties of strategically
      designed boronic acid containing fluorescent sensors, o-, m-, p-BMOQBA, for the
      potential detection of tear glucose concentrations when immobilized in plastic
      disposable contact lenses is described. The new probes, BMOQBAs, consist of the 6
      methoxyquinolinium nucleus as a fluorescent indicator, and the boronic acid
      moiety as a glucose chelating group. A control compound BMOQ, which has no
      boronic acid group and therefore does not bind monosaccharides has also been
      prepared. In this paper, we show that structural design considerations of the new
      probes have afforded for their compatibility within the lenses, with reduced
      probe sugar-bound pK(a) favorable with the mildly acidic lens environment. In
      addition, the new probes are readily water soluble, have high quantum yields, and
      can be prepared by a simple one-step synthetic procedure.

PMID- 15582457
TI  - Facile synthesis of the heptasaccharide repeating unit of O-deacetylated GXM of
      C. neoformans serotype B.
AB  - A heptasaccharide, beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]
      alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp,
      the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar
      B, was synthesized as its methyl glycoside. Thus 2,3,4-tri-O-benzoyl-beta-D
      xylopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-d-mannopyranosyl
      trichloroacetimidate (7) and allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-
      >2)-4,6-di-O-benzoyl-alpha-D-mannopyranoside (8), readily obtained from the
      corresponding monosaccharide derivatives via simple transformation, were coupled
      to give a (1-->3)-linked tetrasaccharide 9. Deallylation of 9 followed by
      trichloroacetimidate formation produced the tetrasaccharide donor 11.
      Condensation of methyl 2,3,4-tri-O-benzoyl-beta-d-xylopyranosyl-(1-->4)-2-O
      acetyl-6-O-benzoyl-alpha-D-mannopyranoside (18) with 11 followed by selective
      deacetylation yielded hexasaccharide acceptor 20. Coupling of 20 with methyl
      2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate bromide (21) and subsequent
      deprotection furnished the target heptaoside. A hexasaccharide fragment, alpha-D
      Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-
      >2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, was also similarly synthesized as its
      methyl glycoside.

PMID- 15582458
TI  - The novel pyrimidine and purine derivatives of l-ascorbic acid: synthesis, one-
      and two-dimensional 1H and 13C NMR study, cytostatic and antiviral evaluation.
AB  - The syntheses of the novel C-5 substituted pyrimidine derivatives of l-ascorbic
      acid containing free hydroxy groups at C-2' (6-10) or C-2' and C-3' (11-15)
      positions of the lactone ring are described. Debenzylation of the 6-chloro- and 6
      (N-pyrrolyl)purine derivatives of 2,3-O,O-dibenzyl-l-ascorbic acid (16 and 17)
      gave the new compounds containing hydroxy groups at C-2' (18) and C-2' and C-3'
      (19 and 20). Z- and E-configuration of the C4'C5' double bond and position of the
      lactone ring of the compounds 6-9 were deduced from their one- and two
      dimensional (1)H and (13)C NMR spectra and connectivities in NOESY and HMBC
      spectra. Compounds 15 and 18 showed the best inhibitory activities of all
      evaluated compounds in the series. The compound 15 containing 5
      (trifluoromethyl)uracil showed marked inhibitory activity against all human
      malignant cell lines (IC(50): 5.6-12.8 microM) except on human T-lymphocytes.
      Besides, this compound influenced the cell cycle by increasing the cell
      population in G2/M phase and induced apoptosis in SW 620 and MiaPaCa-2 cells. The
      compound 18 containing 6-chloropurine ring expressed the most pronounced
      inhibitory activities against HeLa (IC(50): 6.8 microM) and MiaPaCa-2 cells
      (IC(50): 6.5 microM). The compound 20 with 6-(N-pyrrolyl)purine moiety showed the
      best differential inhibitory effect against MCF-7 cells (IC(50): 35.9 microM).

PMID- 15582459
TI  - Synthesis and pharmacological evaluation of 4H-1,4-benzothiazine-2-carbonitrile
      1,1-dioxide and N-(2-cyanomethylsulfonylphenyl)acylamide derivatives as potential
      activators of ATP sensitive potassium channels.
AB  - 1,2,4-Thiadiazine derivatives, like 3-methyl-7-chlorobenzo-4H-1,2,4-thiadiazine
      1,1-dioxide, diazoxide and 7-chloro-3-isopropylamino-4H-benzo-1,2,4-thiadiazine
      1,1-dioxide, BPDZ 73, are potent openers of Kir6.2/SUR1 K(ATP) channels. To
      explore the structure-activity relationship of this series of K(ATP) openers, 4H
      1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2
      cyanomethylsulfonylphenyl)acylamide derivatives were synthesized from 2
      acetylamino-5-chloro-benzenesulfonic acid pyridinium salt or 2
      aminobenzenethiols. The 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide
      derivatives (e.g., 7-chloro-3-isopropylamino-4H-1,4-benzothiazine-2-carbonitrile
      1,1-dioxide, 3f) were found to activate K(ATP) channels as indicated by their
      ability to hyperpolarize beta cell membrane potential, to inhibit glucose
      stimulated insulin release in vitro and to increase ion currents through
      Kir6.2/SUR1 channel as measured by patch clamp. The potency and efficacy of, for
      example, 3f is however significantly reduced compared to the corresponding 4H
      1,2,4-benzothiadiazine 1,1-dioxide derivatives. Opening of the 4H-1,2,4
      thiadiazine ring to get (e.g., 2-cyanomethylsulfonyl-4-fluorophenyl) carbamic
      acid isopropyl ester (4c) gives rise to compounds, which are able to open K(ATP)
      channels but with considerable reduced potency compared to, for example,
      diazoxide. Compound 3a, 7-chloro-3-methyl-4H-1,4-benzothiazine-2-carbonitrile 1,1
      dioxide, which inhibits insulin release in vitro from beta cells and rat islets,
      reduces plasma insulin levels and blood pressure in anaesthetized rats upon
      intravenous administration.

PMID- 15582460
TI  - New antiestrogens from a library screen of homoallylic amides, allylic amides,
      and C-cyclopropylalkylamides.
AB  - A new structural scaffold for antiestrogens was identified from the cell-based
      screening of transcriptional regulation properties of a 67-member library of
      homoallylic amides, allylic amides, and C-cyclopropylalkylamides. C
      Cyclopropylalkylamide 3a (O-ethyl-N-{2-[(1S*,2R*)-2-{(R*)
      [(diphenylphosphinoyl)amino](phenyl)methyl}cyclopropyl]ethyl}-N-[(4
      methylphenyl)sulfonyl]carbamate) had antagonistic activity similar to that of
      tamoxifen and was further evaluated. Compound 3a inhibited estradiol-induced
      proliferation of the ER-positive MCF-7 cells but had no effect on ER-negative MDA
      MB231 human breast cancer cells. Furthermore, high micromolar concentrations of
      3a exhibited minimal cytotoxicity to the ER-negative line. The biological
      activities of the enantiomers of 3a did not differ from one another nor from that
      of racemic 3a.

PMID- 15582461
TI  - Berberine, a strong polyriboadenylic acid binding plant alkaloid: spectroscopic,
      viscometric, and thermodynamic study.
AB  - The interaction of berberine with single stranded poly(rA) structure was
      investigated using a combination of spectrophotometric, spectrofluorimetric,
      circular dichroic, viscometric, and thermodynamic studies. The interaction
      process was characterized by typical hypochromic and bathochromic effects in the
      absorption spectrum of berberine, enhancement of fluorescence intensity of
      berberine, increase of viscosity, and perturbation of circular dichroic spectrum
      of single stranded poly(rA). Scatchard plot obtained from spectrophotometric
      analysis showed that berberine bound strongly to single stranded poly(rA) in a
      non-cooperative manner. In contrast, berberine does not show any significant
      effect (i) in its absorbance and fluorescence spectra on binding to double
      stranded poly(rA), (ii) alter the circular dichroic spectrum of double stranded
      poly(rA), or (iii) increase of viscosity of double stranded poly(rA) indicating
      that it does not bind at all to double stranded poly(rA) structure. Thermodynamic
      parameters indicated that the binding of the alkaloid to single stranded poly(rA)
      is an endothermic process and entropy driven. All these findings, taken together
      clearly support that berberine binds strongly to single stranded poly(rA)
      structure by a mechanism of partial intercalation leading to its use in gene
      regulation in eukaryotic cells.

PMID- 15582462
TI  - Cytotoxic and antitumoral properties in a series of new, ring D modified,
      olivacine analogues.
AB  - The present study describes the synthesis and pharmacological profiles of new
      olivacine related compounds, possessing a modified D ring. The impact of this
      modification has been evaluated with respect to the cytotoxic and in vivo
      antitumoral effects of these molecules and in comparison with parent S 16020-2
      previously prepared and investigated in our laboratory. The D ring size and
      number of nitrogen atoms as well as the position of the aminoalkyl substituent
      have a profound impact on the cytotoxic and antitumoral profiles. Thus out of the
      prepared pyrazinocarbazole compounds, 2 is devoid of any substantial cytotoxic
      and antitumoral activities while the pyrimidocarbazole 3 has a similar profile
      compared to 1 (S 16020-2). L1210 and P388 in vivo antitumoral effects are lost
      for both imidazocarbazoles 4 and 5, but the former conserves an in vivo
      antitumoral effect on B16 melanoma, this effect being the largest in the series.
      Structural similarities and differences amongst the studied compounds could be
      evidenced by calculation of global properties such as molecular electrostatic
      potentials (MEP maps) and partition coefficients (logP), thus adding information
      on the impact of chemical changes on these two parameters known to influence
      biological behavior.

PMID- 15582463
TI  - Fancy bioisosteres: synthesis and dopaminergic properties of the endiyne FAUC 88
      as a novel non-aromatic D3 agonist.
AB  - Enlargement of the pi-electronic system of the non-aromatic D3 agonist FAUC 73
      led to dopaminergic endiynes of type 1 being synthesized via the bromovinyl
      triflate 7a as a key intermediate when palladium catalyzed coupling reactions
      were exploited for the introduction of the (aza)alkyne substituents. As the first
      neuroreceptor active endiyne, FAUC 88 (1c) displayed high and selective dopamine
      D3 receptor affinity (K(ihigh) = 3.2 nM) and substantial ligand efficacy (72%,
      EC(50) = 2.5 nM). Similarities between molecular electrostatic potentials induced
      by the catechol subunit of the genuine neurotransmitter and those of its non
      aromatic endiyne bioisostere are discussed.

PMID- 15582464
TI  - Molluscicidal activity of synthetic lapachol amino and hydrogenated derivatives.
AB  - A series of new amino derivatives and a new partially hydrogenated derivative of
      the natural naphthoquinone lapachol were assayed for molluscicidal activity
      against Biomphalaria glabrata. These derivatives showed low to medium LC(50)
      values, and a 3.1 microg/mL value for the most potent derivative of the series.
      The toxicity is in agreement with the decrease of polar character of the tested
      compounds.

PMID- 15582465
TI  - Synthesis and receptor assay of aromatic-ethynyl-aromatic derivatives with potent
      mGluR5 antagonist activity.
AB  - Noncompetitive antagonists of the human metabotropic glutamate receptor subtype 5
      (mGluR5) have been implicated as potential therapeutics for the treatment of a
      variety of nervous system disorders, including pain, anxiety, and drug addiction.
      To discover novel noncompetitive antagonists to the mGluR5, we initiated an SAR
      study around the known lead compounds MPEP and M-MPEP. Our results pointed out
      the critical role of the para position of the two aromatic rings, which leads to
      inactive products and permitted the discovery of potent mGluR5 antagonists (e.g.,
      16, 25, 28, 34 IC(50) = 13.5, 11.9, 21, 15 nM, respectively).

PMID- 15582466
TI  - Structure-activity relationships for inhibition of human cholinesterases by alkyl
      amide phenothiazine derivatives.
AB  - Several lines of evidence indicate that inhibition of butyrylcholinesterase
      (BuChE) is important in the treatment of certain dementias. Further testing of
      this concept requires inhibitors that are both BuChE-selective and robust. N
      alkyl derivatives (2, 3, 4) of phenothiazine (1) have previously been found to
      inhibit only BuChE in a mechanism involving pi-pi interaction between the
      phenothiazine tricyclic ring system and aromatic residues in the active site
      gorge. To explore features of phenothiazines that affect the selectivity and
      potency of BuChE inhibition, a series of N-carbonyl derivatives (5-25) was
      synthesized and examined for the ability to inhibit cholinesterases. Some of the
      synthesized derivatives also inhibited AChE through a different mechanism
      involving carbonyl interaction within the active site gorge. Binding of these
      derivatives takes place within the gorge, since this inhibition disappears when
      the molecular volume of the derivative exceeds the estimated active site gorge
      volume of this enzyme. In contrast, BuChE, with a much larger active site gorge,
      exhibited inhibition that increased directly with the molecular volumes of the
      derivatives. This study describes two distinct mechanisms for binding
      phenothiazine amide derivatives to BuChE and AChE. Molecular volume was found to
      be an important parameter for BuChE-specific inhibition.

PMID- 15582467
TI  - alpha-Cycloalkyl-substituted omega-keto-dicarboxylic acids as lipid regulating
      agents.
AB  - A series of cycloalkyl-substituted oxo-alkanedicarboxylic acids have been
      prepared by the TosMIC methodology departing from haloalkyl-substituted
      cycloalkylcarboxylic esters. cyclopropyl derivatives showed IC(50) activity in
      the 0.3-1.0 microM range on the de novo incorporation of radiolabeled acetate
      into lipids in primary cultures of rat hepatocytes, and they showed lipid
      regulating properties when tested in vivo in female obese Zucker fatty rats.

PMID- 15582468
TI  - On the role of polarizability in QSAR.
AB  - The polarizability of a molecule, an important physical property, is currently
      attracting our attention particularly in the area of QSAR for chemical-biological
      interactions. In this report, the polarizability effects on ligand-substrate
      interactions has been discussed in terms of NVE (number of valence electrons)
      using additive values for valence electrons and the formulation of a total number
      of 51 QSAR. The QSAR model can be illustrated by Eq. I. log 1/C = a(NVE) +/-
      constant

PMID- 15582469
TI  - Identification and characterization of nonsubstrate based inhibitors of the
      essential dengue and West Nile virus proteases.
AB  - The 72 known members of the flavivirus genus include lethal human pathogens such
      as Yellow Fever, West Nile, and Dengue viruses. There is at present no known
      chemotherapy for any flavivirus and no effective vaccines for most. A common
      genomic organization and molecular mechanisms of replication in hosts are shared
      by flaviviruses with a viral serine protease playing a pivotal role in processing
      the viral polyprotein into component polypeptides, an obligatory step in viral
      replication. Using the structure of the dengue serine protease complexed with a
      protein inhibitor as a template, we have identified five compounds, which inhibit
      the enzyme. We also describe parallel inhibitory activity of these compounds
      against the West Nile virus Protease. A few of the compounds appear to provide a
      template for design of more potent and specific inhibitors of the dengue and West
      Nile virus proteases. Sequence similarities among flaviviral proteases suggests
      that such compounds might also possibly inhibit other flaviviral proteases.

PMID- 15582470
TI  - Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3
      carboxylic acid derivatives as antimitotic agents.
AB  - As part of a continuing search for potential anticancer drug candidates in the 2
      phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic
      acid derivatives and their salts were synthesized and evaluated. Preliminary
      screening showed that carboxylic acid analogs containing a m-fluoro substituted 2
      phenyl group displayed the highest in vitro anticancer activity. Activity
      decreased significantly if a chlorine or methoxy group replaced the fluorine
      atom. 3'-Fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (68) had the
      highest in vitro cytotoxic activity among all tested carboxylic acid derivatives
      and their salts. The mechanism of action may be similar, but not identical, to
      that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits
      further investigation as a novel hydrophilic antimitotic agent.

PMID- 15582471
TI  - Synthesis of 2',3'-dideoxy-2'-monofluoromethyl azanucleosides.
AB  - (2S,4S)-Methyl-N-tert-butoxycarbonyl-4-monofluoromethylpyroglutamate 6 was
      synthesized via a key dehydrofluorination followed by hydrogenation. Compound 6
      was converted to (5S,3S)-N-benzyloxycarbonyl-5-tert-butyldimethylsilyloxymethyl-3
      monofluoromethyl-2-pyrrolidone 12 over four steps in 62% yield, which was used as
      a precursor for the synthesis of 2',3'-dideoxy-2'-monofluoromethyl azanucleosides
      17-18.

PMID- 15582472
TI  - Energy-filtered TEM imaging and EELS study of ODS particles and argon-filled
      cavities in ferritic-martensitic steels.
AB  - Oxide-dispersion-strengthened (ODS) ferritic-martensitic steels with yttrium
      oxide (Y(2)O(3)) have been produced by mechanical alloying and hot isostatic
      pressing for use as advanced material in fusion power reactors. Argon gas,
      usually widely used as inert gas during mechanical alloying, was surprisingly
      detected in the nanodispersion-strengthened materials. Energy-filtered
      transmission electron microscopy (EFTEM) and electron energy loss spectroscopy
      (EELS) led to the following results: (i) chemical composition of ODS particles,
      (ii) voids with typical diameters of 1-6 nm are formed in the matrix, (iii) these
      voids are filled with Ar gas, and (iv) the high-density nanosized ODS particles
      serve as trapping centers for the Ar bubbles. The Ar L(3,2) energy loss edge at
      245 eV as well as the absorption features of the ODS particle elements were
      identified in the EELS spectrum. The energy resolution in the EEL spectrum of
      about 1.0 eV allows to identify the electronic structure of the ODS particles.

PMID- 15582473
TI  - In situ TEM observation of the nucleation and growth of silver oxide
      nanoparticles.
AB  - The nucleation, growth, and coalescence of silver oxide nanoparticles have been
      investigated dynamically and at high spatial resolution by using the electron
      beam of a transmission electron microscope to stimulate and to observe the
      processes. Under the assumption the particles are hemispherical, the growth rate
      was found to be proportional to the square root of the electron irradiation time.
      This result suggests that the rate-limiting step is the attachment of atoms to
      the nanoparticles. Growth of the nanoparticles occurred by the addition of
      columns of atoms on {111} planes. Particle impingement resulted in
      interpenetration of the particles and, ultimately, the formation of a grain
      boundary.

PMID- 15582474
TI  - Some morphological aspects of Wuchereria bancrofti uterus after treatment with
      diethylcarbamazine.
AB  - Confocal and EM analyses revealed that some female Wuchereria bancrofti, obtained
      from volunteers that received recommended diethylcarbamazine dose regimens,
      showed few or no embryos. Furthermore, inside the gravid uterus of female W.
      bancrofti treated with DEC we observed a finely granular, electron-dense material
      organised as strings of pearls, approximately 70 nm in maximal length surrounding
      intra-uterine microfilariae and apparently secreted by the embryo. Over the
      eggshells a similar material was also observed, possibly secreted by the uterine
      wall. The surface of intra-uterine microfilariae presented a material with
      identical electron-density to the scattered structures observed inside the egg.
      Similarly, the sheath of blood microfilariae of W. bancrofti also showed electron
      dense projections, with shape and size similar to that observed inside the
      uterus.

PMID- 15582475
TI  - Iterative reconstruction of in-line electron holograms.
AB  - In low energy electron point source (LEEPS) microscopy, electrons emerge from a
      point source, propagate as spherical waves, and arrive at a screen. Some
      electrons scatter off an object, i.e. a cluster of atoms, placed between the
      source and the screen; others arrive at the screen without scattering. The
      interference pattern on the screen, an electron hologram, is used to reconstruct
      the object by calculating and analyzing a function K(r) in the region occupied by
      the object. We present an iterative method that uses the original reconstruction
      K(o)(r) to determine the atomic configuration of the object. No knowledge of the
      object, except for the vicinity in which the object is located, is used in the
      iterative scheme. In particular, no knowledge of the atomic structure is used.
      The method uses K(o)(r) to make a test object that in turn gives another
      reconstruction K(1)(r); K(1)(r) and K(o)(r) are used to modify the test object
      and obtain K(2)(r). The iteration is repeated until it converges on a final
      object that gives a reconstruction K(f)(r) that is very similar to K(o)(r). The
      final object gives an atomic structure that is close to the atomic structure of
      the original object. Results for several idealized objects are presented and
      discussed.

PMID- 15582476
TI  - Tomographic reconstruction of multiple in-line electron holograms of realistic
      objects.
AB  - In theoretical low energy electron point source microscopy, simulated holograms
      are made and used to reconstruct atomic clusters. In previous investigations,
      simple test clusters were used for convenience. In this paper we explore more
      realistic structures composed of a single type of atom such as diamond, graphite
      and Buckminsterfullerene--all of which consist of carbon atoms. We also examine
      clusters with two or more distinct atom types, including TiO(2), CuO, Pt(3)O(4),
      Ga(3)Pt(5), WC, MgCO(3), and MgO. Reconstructions from a single hologram do not
      give atomic resolution, and consist instead of 'spurious peaks' that are not
      located at atomic sites, as well as 'atomic peaks' close to atomic sites. Here we
      apply methods we developed previously to remove all spurious peaks. We show final
      reconstructions that consist only of atomic peaks located very close to atomic
      sites.

PMID- 15582477
TI  - New findings in phase transitions of spinel Li1.07Mn1.93O4-delta studied by
      transmission electron microscopy.
AB  - Phase transitions and the related phase identifications at different temperatures
      for spinel Li(1.07)Mn(1.93)O(4-delta) crystals have been studied by transmission
      electron microscopy. The preliminary results clearly show the existence of at
      least two types of low-temperature phase: monoclinic and orthorhombic. Oxygen
      deficiency may raise the phase-transition temperature for the high-temperature
      (HT) cubic to low-temperature (LT) tetragonal, monoclinic, or orthorhombic
      phases. When the oxygen deficiency delta is very close to zero, the transition
      temperature is below room temperature (RT). Therefore, only the HT cubic spinel
      is observed at RT. When delta=0.182, the transition temperature is higher than
      RT, so the structures of the LT phases can be studied at RT. This study reveals
      the structural relationships between the LT phase and the HT phase. These
      relationships can be summarized as follows: (1) Two orthogonal cubic
      [440](Cubic)(*) and [440](Cubic)(*) reciprocal vectors are divided into two parts
      by {220} and {220} super reflections, respectively. This situation resembles the
      structures caused by correlated tilting and/or distortion of the octahedra in
      perovskites. (2) One of the cubic <440>Cubic(*) reciprocal vectors is divided
      into three parts by weak super-reflections. This situation resembles the
      modulated structure caused by the charge- and orbital-ordering in the perovskite
      La(1/3)Ca(2/3)MnO(3) of the space group Pnma. (3) One of the cubic
      <440>(Cubic)(*) reciprocal vectors, e.g. [440](Cubic)(*), is divided into three
      parts by stronger super-reflections, at the same time some strong reflections of
      the cubic spinel, e.g. (111)(Cubic)=(320)(Ortho)/2 disappear, indicating that
      there is a phase transition containing atomic movement. Items (2) and (3) are new
      findings in the present work.

PMID- 15582478
TI  - Large-scale fabrication and characterization of Cd-doped ZnO nanocantilever
      arrays.
AB  - We demonstrate bulk synthesis of highly crystalline Cd-doped ZnO nanocantilever
      arrays (CZNAs) using Cd and Zn powders at 600 degrees C, which is characterized
      via scanning electron microscopy, powder X-ray diffraction, X-ray photoelectron
      spectroscopy, transmission electron microscopy (TEM), energy dispersive X-ray
      spectroscopy, selected area electron diffraction, and high resolution TEM. The
      results show that the as-prepared CZNAs have diameters of about 15-50 nm, and
      lengths up to 400 nm and the corresponding process of growth is suggested for
      conventional vapor solid mechanism.

PMID- 15582479
TI  - Structural aspects of the Eberth-Katschenko layer of Bufo ictericus integument:
      histochemical characterization and biochemical analysis of the cutaneous calcium
      (Amphibian, Bufonidae).
AB  - Anuran, such as Brazilian toad Bufo ictericus Spix, 1824, possess a calcified
      dermal layer called the Eberth-Katschenko (EK) layer located between the stratum
      spongiosum and the stratum compactum. It has been regarded as a protective
      barrier against desiccation or involved in storage and mobilization of calcium,
      or a barrier for the interchange of substances between the animal's internal and
      external environment. The B. ictericus integument was removed from the ventral
      and dorsal regions and examined by light microscopy, using histochemical
      techniques, and also submitted to biochemical calcium analysis. The intermediate
      layer is strongly basophilic and metachromatic. In the EK layer Alcian blue at
      different critical electrolytic concentration revealed hyaluronic acid, which
      coexists with the dermal calcium. We conclude that the EK layer of B. ictericus
      is a discontinuous layer and is formed of hyaluronic acid and a sulfated GAG
      different from chondroitin sulfate, heparin and heparan sulfate or keratan
      sulfate. The amount of cutaneous calcium is independent of region and sex. GAGs
      may play an important role in dermal hydric balance, protecting the animal
      against desiccation, and hyaluronic acid is probably able to anchor dermal
      calcium. Thus, all compounds of the EK layer are essential for integument
      integrity and functionality.

PMID- 15582480
TI  - The ultrastructure of infective larvae (L3) of Wuchereria bancrofti after
      treatment with diethylcarbamazine.
AB  - Although the large use of diethylcarbamazine (DEC), as the major anti-filaricide
      drug, its mechanism of action remains a matter of controversy. Several authors
      defend the hypothesis that DEC has no direct effect on nematodes. This study
      demonstrated that infective larvae (L3) of Wuchereria bancrofti treated in vitro
      with DEC presented several behaviour and morphological changes. The first
      alteration produced by treatment for 2 h with 3, 5, 10 microg/ml of DEC was the
      reduction of motility. Larvae treated with 5, 10 microg/ml DEC showed severely
      affected organelles, formation of several vacuoles, mainly in neurocytes and in
      the muscle cells, and dissolution of cytoplasm. Some larvae showed extreme
      cellular disorganization with abundance of large and dense mitochondria and
      numerous large vacuoles containing residual organelles. Lamellar bodies, probably
      related to an assembly of hipodermal membranes, were also observed in some
      damaged larvae. Thus, undoubtedly in vitro treatment with concentrations of DEC
      similar to therapeutic conditions, which are 1-5 microg/ml (Hawking, 1979), had a
      direct effect on infective larvae of W. bancrofti by causing, primarily
      neuromuscular alterations with subsequent damage to organelles.

PMID- 15582481
TI  - Ultrastructural analysis of Vitis vinifera leaf tissues showing atypical symptoms
      of Plasmopara viticola.
AB  - In an abandoned farm in Tuscany a year by year regression of downy mildew disease
      on grapevines was observed and a decrease in virulence as well as vigor and
      fertility of the causal fungus, Plasmopara viticola. Anomalous spots of the
      fungus (i.e. atypical coloration of leaves or mosaic) on leaf tissues of a
      sensitive Vitis vinifera grapevine were observed. The anomalous symptoms were
      often associated with the typical 'oil spots' and were present under
      environmental conditions favourable for a normal development of the disease. An
      ultrastructural study was carried out on leaf tissues of grapevine plants aimed
      at clarifying the cause of this phenomenon and detecting whether there were
      alterations in P. viticola mycelium and endophytes present. ELISA was also
      performed to check the presence of grapevine viruses in the plants. TEM results
      demonstrated that characteristic P. viticola was present in leaf samples showing
      oil spots, while, both the fungus and the host tissues showed cytological
      alterations in leaves with mosaic symptoms. Finally, hyphae were absent in leaf
      tissues without downy mildew spots, but showing severe ultrastructural
      modifications. Several plant virus infections were found in these grapevines.
      Literature reports that the development and sporulation of some phytopathogenic
      fungi inside their hosts can be limited by virus infections. Further experimental
      approaches are required to determine if resistance to P. viticola can be induced
      by viral infections in grapevines.

PMID- 15582482
TI  - TEM and HREM of diamond crystals grown on Si tips: structure and results of ion
      beam-treatment.
AB  - Diamond single crystals were grown on the silicon whiskers by a hot filament
      chemical vapor deposition technique at the filament temperature about 2100
      degrees C and the temperature of support 800 degrees C. Specimens were examined
      by SEM, TEM, HRTEM and SAED. When the filament temperature was about 1900 degrees
      C globular polycrystalline diamond particles were grown. At a support temperature
      more then 800 degrees C SiC nanoparticles were formed. To investigate the ion
      etching process of the silicon tip/diamond system, tips were treated with an
      Ar(+) beam with energy up to 30 kV. The results depend on fluence: at 4 x
      10(18)ion/cm(2) diamonds and partially Si tips were destroyed, amorphous layer
      was formed (sometimes with nanometric size fragments of diamond); at 1 x
      10(18)ion/cm(2) sharpened diamonds (radius of curvature about 20 nm) covered with
      amorphous layer (radius about 80 nm) probably with nanoclusters of diamond were
      observed; at 4.4 x 10(17) ion/cm(2) there was no visible tip sharpening but
      formation of amorphous thick layer occurred. The emission characteristics of Si
      tips covered with diamond were improved due to ion treatment. Since such tips in
      our case were covered with amorphous layer containing nanometric size fragments
      of diamond, we suppose this layer is responsible for electron emission
      improvement.

PMID- 15582483
TI  - Structural aspects of an unusual choroidal polarized hyaline cartilage in the
      eyeball of Bufo ictericus and Rana catesbeiana (Amphibia, Anura): morphological
      and physiological significance.
AB  - Amphibian eyes play an important role in vision and in several physiological
      processes, such as food capture and breathing. To maintain the integrity of the
      eyeball there is a unique cuplike hyaline cartilage as a supporting tissue. In
      Bufo ictericus and Rana catesbeiana the cartilage layer is located between the
      retina and the choroids, being designated as choroidal cartilage, important to
      visual performance. On the retinal surface, there is no perichondrium, and the
      pigmented epithelium exhibits an intimate relationship to the cartilage layer.

PMID- 15582484
TI  - Spatial organization in immune cell signaling.

PMID- 15582485
TI  - Single-molecule tracking of membrane molecules: plasma membrane
      compartmentalization and dynamic assembly of raft-philic signaling molecules.
AB  - Tracking single molecules in the plasma membrane in live cells is becoming a
      useful technique for studying the spatial-temporal control of membrane molecular
      processes, such as signal transduction and the formation of large molecular
      complexes. In this review, three topics largely based on recent single-molecule
      observations are described, with a special emphasis on the results that are
      considered to be difficult to obtain using conventional methods monitoring the
      ensemble-averaged behavior of molecules. First, we describe the high-speed single
      molecule tracking data, mostly obtained by our group that necessitated the
      paradigm shift of the plasma membrane structure, from the two-dimensional
      continuum fluid model to the compartmentalized fluid model. Second, we try to
      present a synthetic view of the cell membrane, which contains raft and other
      microdomains as well as being partitioned into small compartments. Furthermore,
      we present our working hypothesis, based on the literature, how large, stabilized
      rafts may be formed, after ligation or crosslinking, from small/unstable
      "reserve" rafts present in the steady-state cells. Finally, we explain our
      initial application of single-molecule fluorescence imaging for studies of the
      creation of T-cell receptor signaling complexes (immunological synapses or
      SMACS), by observing the recruitment of single Lck molecules as an initial
      approach. This revealed that the assembly of Lck at the T-cell receptor cluster
      site, observed by conventional fluorescence microscopy, actually represents
      dynamic concentrations of Lck molecules, entering and exiting the cluster domain
      rapidly, with the aid of the raft domains.

PMID- 15582486
TI  - Lipid rafts and the initiation of T cell receptor signaling.
AB  - The role of lipid rafts in T cell signalling has recently been extensively
      studied and hotly debated. In this review we wish to present recent advances in
      the study of lipid rafts with regards to the initiation of TCR signal
      transduction. We also wish to clarify some common misconceptions regarding
      certain models and experimental methods reported in the literature. Based on the
      relevant data supporting the functional importance of lipid rafts in early TCR
      mediated signalling events, we propose a model for TCR signal initiation
      involving a "TCR signalosome" organized in a specific raft subset, which is
      highly dynamic and evolving upon TCR activation.

PMID- 15582487
TI  - Right time, right place: the organization of membrane proximal signaling.
AB  - The basic mechanisms of lymphocyte activation are well established, with
      stimulation via the antigen receptor inducing a rapid wave of tyrosine
      phosphorylation that requires the coordinated action of multiple protein tyrosine
      kinase families. This in turn leads to the generation of second messengers like
      Ca(2+), diacylglycerol (DAG) and inositoltrisphosphate (IP(3)) as well as the
      activation of effector molecules like Ras and the mitogen-activated protein
      kinases (MAPKs) and ultimately in activation of the transcription factors NFAT,
      AP-1, and NF-kappaB, resulting in gene transcription. Researchers, hoping to
      interconnect these events, have identified a multitude of proteins, among which
      is a relatively new group, the transmembrane adaptor proteins (TRAPs). TRAPs are
      unique in that they lack extracellular ligands and possess neither enzymatic nor
      transcriptional activity, but rather serve as scaffolds providing docking sites
      for other proteins and thereby serving to coordinate signals proximal to the
      membrane. Our study of these novel molecules is shedding new insights into the
      positive and negative regulatory mechanisms which fine tune antigen receptor
      signaling.

PMID- 15582488
TI  - Multi-chain immune recognition receptors: spatial organization and signal
      transduction.
AB  - Multi-chain immune recognition receptors (MIRRs) on T cells, B cells, mast cells
      and basophils function to transduce signals leading to a variety of biologic
      responses. These receptors are complexes formed by the association of
      immunoglobulin-like recognition subunits and signal-transducing subunits. How
      extracellular ligand binding initiates intracellular signal transduction
      processes is not clear, and little structural or biochemical information is
      available for the spatiotemporal organization of this key event in immune cell
      activation. Here, the current progress in studying this important aspect of
      cellular signaling is reviewed.

PMID- 15582489
TI  - T cell synapse assembly: proteins, motors and the underlying cell biology.
AB  - A tantalizing feature of the 'immunological synapse' is the segregation of
      transmembrane proteins into activating clusters and their underlying
      signalosomes. The mechanisms by which transmembrane proteins are initially
      recruited to and then stably segregated at the synapse remains an outstanding
      question in the field; and one likely to reveal key modes of signaling
      regulation. Ongoing real-time imaging approaches and a refocusing of efforts upon
      understanding the basic cell biology of T cells have all contributed to a
      developing model of T cell behavior; elementary TCR-derived signaling quickly
      feeds back into the basic cellular programs controlling cell shape, adhesiveness,
      motility, as well as some poorly understood aspects of membrane fluidity and
      segregation. It is increasingly clear that the mechanisms for control at this
      level are shared between T cells and other cell types and may not be revealed in
      differential genomic screening. To this end, imaging-based genetic screens are
      now coming online to aid in identifying the ubiquitous proteins that function at
      polarized signaling surfaces.

PMID- 15582490
TI  - Mastering time and space: immune cell polarization and chemotaxis.
AB  - Many immune cells can detect the direction and intensity of an extracellular
      chemical gradient, and migrate toward the source of stimulus. This process,
      called chemotaxis, is essential for immune system function and homeostasis, and
      its deregulation is associated with serious diseases. Chemotaxis is initiated by
      chemoattractant binding to heterotrimeric G protein-coupled receptors, which
      translate the gradients into accurate directional migration. A necessary step in
      this process is cell polarization, the acquisition of functional and spatial
      asymmetry. The use of new imaging technologies enables analysis of spatial and
      temporal changes in the activity of proteins and membrane domains involved in
      polarization and chemotaxis. We discuss the sometimes contradictory evidence
      available and the emerging molecular model for immune cell polarity and
      chemotaxis.

PMID- 15582491
TI  - CTL secretory lysosomes: biogenesis and secretion of a harmful organelle.
AB  - Cytotoxic T cells (CTL) clear virally infected cells and tumorigenic cells. CTL
      kill their targets by releasing very potent cytotoxic proteins stored in
      preformed secretory organelles termed secretory lysosomes. The accurate killing
      is assured by a vectorial movement of secretory lysosomes along microtubules and
      focused secretion within the immunological synapse. Some of the proteins
      controlling these secretion steps have been identified studying CTL from patients
      affected by severe immunodeficiency. Here we present an over view of how these
      key regulators such as AP-3 adaptor protein, RabGGTase enzyme, Rab27a small GTP
      binding protein, Lyst and Munc13-4 act in a very orchestrated way to deliver the
      "kiss of the death".

PMID- 15582492
TI  - Thymopoiesis in 4 dimensions.
AB  - Developing T cells undergo long-range migrations in the thymus that are tightly
      linked to their developmental program. In this review, we discuss the anatomical
      positioning of developing T cells in the thymus, review what we know about how
      cells move in the thymus, and point out unresolved questions. We also discuss new
      imaging technologies and interdisciplinary approaches and discuss how the promise
      they offer to addressing these questions.

PMID- 15582493
TI  - Stretching the surface epithelium.

PMID- 15582494
TI  - Ontogeny of vascular growth factors in perinatal sheep myocardium.
AB  - OBJECTIVE: To examine developmental changes in myocardial gene expression of
      previously identified regulators of vascular growth. METHODS: Ovine left (LV) and
      right ventricle (RV) samples were obtained at four time points: 95 days' and 140
      days' gestation (term = 145 days) and 7 days and 8 weeks postnatally. mRNA and
      protein levels of vascular endothelial growth factor (VEGF), its respective
      receptors (Flk-1 and Flt-1), basic fibroblast growth factor (bFGF), transforming
      growth factor-beta1 (TGF-beta1), and endothelial nitric oxide synthase (eNOS)
      were measured at these different time points. RESULTS: RV but not LV VEGF mRNA
      levels decreased postnatally, although VEGF protein expression remained unchanged
      after birth. Flt-1 mRNA expression was divergent between ventricles, although the
      protein expression pattern was similar in RV and LV, decreasing with maturation.
      RV and LV Flk-1 mRNA decreased between 95 days and 140 days, remaining stable
      thereafter, while protein levels only decreased after birth. bFGF protein levels
      were highest in the LV at 140 days, and decreased after birth but remained
      unchanged in the RV throughout the period examined. TGF-beta1 and eNOS levels
      were highest early in gestation, decreasing with maturation in both ventricles.
      CONCLUSION: Developmentally regulated ventricle-specific expression of VEGF, Flt
      1, Flk-1, TGF-beta1, bFGF, and eNOS was demonstrated in the ovine myocardium.
      These findings suggest these proteins may participate in coronary vascular
      remodeling during the perinatal period and underscore the importance of studying
      the relationships among transcription factors, target genes, and
      anatomic/physiologic changes in the whole animal.

PMID- 15582495
TI  - Chronic hypoxia inhibits contraction of fetal arteries by increased endothelium
      derived nitric oxide and prostaglandin synthesis.
AB  - OBJECTIVE: Chronic hypoxia causes redistribution of fetal cardiac output by
      mechanisms poorly understood. We tested the hypothesis that chronic hypoxia
      alters vascular reactivity of arteries from near-term fetal guinea pigs. METHODS:
      Pregnant guinea pigs (50 days, term = 65 days) were exposed to either normoxia
      (room air) or hypoxia (12% O2) for 14 days. Carotid artery ring segments from
      anesthetized fetuses were mounted onto myographs for measurement of force.
      Contractile responses to cumulative addition of prostaglandin F2alpha (PGF2alpha,
      10(-9) M to 10(-5) M), U46619, a thromboxane mimetic (10(-12) M to 12(-6) M), and
      KCl (10 to 120 mM) were measured in the presence and absence of INDO (INDO, 10(
      5) M) alone and INDO plus nitro-L-arginine (LNA, 10(-4) M), or INDO plus N6
      iminoethyl-L-lysine (LNIL, 5 x 10(-5) M, a selective iNOS inhibitor), and
      measured in endothelium-intact and denuded arteries. Nitric oxide synthase (NOS)
      activity was measured in isolated arteries by 14C-L-arginine to 14C-L-citrulline
      conversion. RESULTS: Hypoxia decreased contractile responses to both PGF2alpha
      and U46619 under control conditions. Maximal contraction to both agonists was
      increased in hypoxemic arteries after INDO alone and INDO + LNA compared to
      normoxic controls. Endothelium-denudation abolished the differences between the
      groups. KCl contraction was unaffected by hypoxia. LNIL potentiated maximal
      PGF(2alpha) contraction but was similar between groups. Hypoxia increased (P <
      .05) total and Ca(2+)-dependent NOS activities by 1.7- and 2.1-fold,
      respectively, but had no effect on Ca(2+)-independent activity. CONCLUSION:
      Chronic hypoxia alters vascular reactivity of fetal carotid arteries by
      increasing the contribution of both vasodilator prostaglandins and nitric oxide
      and suggests that changes in local vascular mechanisms may be altered by chronic
      hypoxia.

PMID- 15582496
TI  - Morphologic alterations in ovine placenta and fetal liver following induced
      severe placental insufficiency.
AB  - OBJECTIVES: Umbilical-placental embolization with microspheres has been used as a
      model of placental insufficiency and intrauterine growth restriction (IUGR).
      However, the effects of embolization on placental structure and organ morphology
      of the resulting IUGR fetus are relatively unexplored. In this study using ovine
      fetuses, we determined the location and distribution of microspheres within the
      placenta and explored the extent of placental and fetal organ morphologic changes
      induced by placental embolization. We hypothesized that microspheres administered
      into the umbilical circulation over 4 days would cause placental damage without
      significant morphologic alterations in fetal kidney or liver. METHODS: Eleven
      pregnant sheep at 118 +/- 1 (SE) days' gestation were studied. In six fetuses,
      embolization was induced by injections of 15-microm diameter microspheres on 4
      successive days into the fetal descending aorta proximal to the umbilical
      arteries. Five fetuses served as time controls. RESULTS: In embolized fetuses,
      microspheres were detected in the placenta embedded in the fetal
      cytotrophoblastic layer or maternal parenchyma adjacent to villous
      cytotrophoblasts. Fetal cytotrophoblasts appeared normal except for loss of
      distinct separation between fetal and maternal cell layers. Microspheres were
      also detected in the fetal membranes within capillaries. The body weights of
      embolized fetuses were lower than controls, as were the body weight-normalized
      liver but not kidney weights. In the liver of the embolized fetuses, the number
      of hematopoietic cell clusters was markedly reduced, whereas the fetal kidneys
      appeared normal. CONCLUSIONS: We conclude that after 4 days of umbilical
      placental embolization, microspheres were concentrated at the fetal villi
      proximal to the apical maternal-fetal interface and in the fetal membranes. There
      were noticeable morphologic changes in the embolized placentas, with no apparent
      gross damage to the placenta. The reduction in fetal liver weight and liver
      extramedullary hematopoietic cell abundance associated with embolization may
      predispose the fetus to alterations in liver function that could persist after
      birth.

PMID- 15582497
TI  - Estrogen receptor-alpha agonists promote angiogenesis in human myometrial
      microvascular endothelial cells.
AB  - OBJECTIVE: The relative role of the two estrogen receptors, ERalpha and ERbeta,
      in mediating angiogenic responses in adult human endothelium is unknown. The aim
      of this study was to determine whether novel ERalpha-selective agonists, propyl
      pyrazole triol (PPT) and the tetrahydrochrysene (R,R-THC), up-regulate the
      expression of vascular endothelial growth factor receptor-2 (VEGFR-2), and
      promote VEGF-stimulated endothelial cell proliferation in primary cultures of
      adult female microvascular endothelial cells co-expressing endogenous ERalpha and
      ERbeta. METHODS: Confluent primary cultures of microvascular endothelial cells
      isolated from human myometrium were incubated with 17beta-estradiol (1 and 10
      nM), PPT (10 nM to 3 microM), or R,R-THC (10 nM to 3 microM) for 18 hours and
      VEGFR-2 expression measured by biotin-VEGF165 binding and flow cytometry.
      Endothelial cell proliferation was assessed in microvascular endothelial cells
      after incubation with 17beta-estradiol (10 nM), PPT (100 nM), and R,R-THC (100
      nM) for 6 days using a tetrazolium-based bioassay. RESULTS: Both PPT and R,R-THC
      increased VEGFR-2 expression on myometrial microvascular endothelial cells in a
      dose-dependent manner, reaching a maximum at 1 microM. Approximately 40% of
      myometrial microvascular endothelial cell isolates only express ERbeta and do not
      express ERalpha, and in these neither PPT, R,R-THC, nor 17beta-estradiol
      increased VEGF binding. PPT- or R,R-THC-stimulated increase in VEGF binding was
      significantly different between ERalpha+ and ERalpha- microvascular endothelial
      cell samples (P < .001 and P < .05, respectively). PPT, R,R-THC, and 17beta
      estradiol significantly augmented VEGF-stimulated microvascular endothelial cell
      proliferation in ERalpha+ (P < .05), but not in ERalpha- samples. CONCLUSIONS:
      This angiogenic effect of 17beta-estradiol on adult female microvascular
      endothelial cells is mediated by ERalpha, rather than ERbeta.

PMID- 15582498
TI  - Effects of polyamines on human umbilical artery tone in vitro.
AB  - OBJECTIVE: Polyamines act as endogenous modulators of cell function and
      excitability. There are no data in relation to their effects on the human
      fetoplacental circulation. The aim of this study was to investigate the effects
      of the polyamines, spermine, and spermidine on human umbilical artery resistance
      in vitro. METHODS: Isometric tension recordings were performed under physiologic
      conditions on human umbilical arterial rings (n = 12). The in vitro effects of
      spermine and spermidine (at concentrations ranging between 10(-9) M to 10(-3) M)
      were measured, and compared with those measured in vehicle control experiments.
      The maximal inhibition (MMI) at the highest concentration and the pD2 (-log EC50)
      values for each compound were calculated and compared. RESULTS: Spermine and
      spermidine exerted a potent relaxant effect on human umbilical arterial tone in
      comparison to vehicle control experiments. The MMI +/- SEM for spermine was 18.41
      +/- 1.437% (n = 6; P <.001) and for spermidine was 38.31 +/- 3.572% (n = 6; P
      <.001). There was no difference observed between the pD2 +/- SEM values for
      spermine (5.78 +/- 1.54; n = 6) and spermidine (6.27 +/-0.85; n = 6) (P = .517).
      CONCLUSION: The polyamines spermine and spermidine exert a potent relaxant effect
      on human umbilical artery tone suggestive of an endogenous role for these
      compounds in vasomotor regulation of the fetoplacental circulation.

PMID- 15582499
TI  - Low-activity haplotype of the microsomal epoxide hydrolase gene is protective
      against placental abruption.
AB  - OBJECTIVE: We wanted to determine whether genetic variability in the gene
      encoding microsomal epoxide hydrolase (EPHX) contributes to individual
      differences in susceptibility to the occurrence of placental abruption. METHODS:
      The study involved 117 women with placental abruption and 115 healthy control
      pregnant women who were genotyped for two single nucleotide polymorphisms (SNPs),
      T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene.
      Chi-square analysis was used to assess genotype and allele frequency differences
      between the women with placental abruption and the control group. In addition,
      single-point analysis was expanded to pair of loci haplotype analysis to examine
      the estimated haplotype frequencies of the two SNPs, of unknown phase, among the
      women with placental abruption and the control group. Estimated haplotype
      frequencies were assessed using the maximum-likelihood method, employing an
      expectation-maximization algorithm. RESULTS: Single-point allele and genotype
      distributions in exons 3 and 4 of the EPHX gene were not statistically different
      between the groups. However, in the haplotype estimation analysis we observed a
      significantly decreased frequency of haplotype C-A (His113-His139) among the
      placental abruption group compared with the control group (P = .007). The odds
      ratio for placental abruption associated with the low-activity haplotype C-A
      (His113-His139) was 0.552 (95% confidence interval, 0.358 to 0.851). CONCLUSIONS:
      The use of two intragenic SNPs jointly in haplotype analysis of association
      demonstrated that the genetically determined low-activity haplotype C-A (His113
      His139) was significantly less frequent in women with placental abruption.

PMID- 15582500
TI  - An image analysis technique for the investigation of variations in placental
      morphology in pregnancies complicated by preeclampsia with and without
      intrauterine growth restriction.
AB  - OBJECTIVE: The purpose of this study was to use visual image analysis to observe
      changes in the morphology and composition of placental villi in pregnancies
      complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR).
      METHODS: Placental biopsies from nine normal pregnancies, five cases of PE, five
      cases of IUGR, and five cases of PE with IUGR (PE x IUGR) were randomly sampled.
      Formalin-fixed, wax-embedded sections were stained with hematoxylin and eosin
      (H&E) and subjected to image analysis. The placental areas occupied by villi,
      syncytiotrophoblast, and syncytial cytoplasm and nuclei were quantified. RESULTS:
      Significantly smaller placentas were obtained from growth-restricted pregnancies.
      PE, with and without IUGR, had no effect on the total area occupied by villi or
      intervillous space. IUGR alone showed a real and consistent reduction in villous
      area (56.0 +/- 2.4% vs 43.6 +/- 3.3%, P <.03). While the ratio of syncytial to
      villous areas were noticeably reduced in all cases of PE (0.38 +/- 0.03 vs 0.24
      +/- 0.07, P <.05), this ratio remained unchanging in IUGR. Birth weight was
      positively correlated to both placental size and total villous area occupied.
      Moreover, increasingly positive relationships were recorded between both
      syncytiotrophoblast area and syncytiotrophoblast cytoplasm and birth weight (P
      <.01 and P <.001, respectively). CONCLUSION: These measurements point to
      impoverished villus development in idiopathic IUGR. The observed changes in PE
      with IUGR were more akin to PE without growth restriction than IUGR alone. This
      suggests that idiopathic IUGR and IUGR in PE have a separate etiology, idiopathic
      IUGR arising through a reduction in villous area alone, and IUGR in PE caused by
      changes in syncytiotrophoblast quantity, more specifically the amount of
      syncytiotrophoblast cytoplasm.

PMID- 15582501
TI  - Telomerase prolongs the lifespan of normal human ovarian surface epithelial cells
      without inducing neoplastic phenotype.
AB  - OBJECTIVE: The aim of this study was to determine the effects of exogenous
      expression of the catalytic subunit of telomerase (hTERT) on the lifespan, growth
      characteristics, and tumorigenicity of normal human ovarian surface epithelial
      (OSE) cells. METHODS: Low-passage primary cultures of normal human OSE cells were
      transfected with hTERT and the resulting cell lines were characterized. RESULTS:
      The ectopic expression of hTERT stabilized the telomeres of the OSE cultures
      above 8 kb. The hTERT-transfected OSE cell lines grew beyond the normal lifespan
      seen in OSE cells and propagated in culture for more than 40 passages before
      senescing. Moreover, the hTERT-transfected cells demonstrated extensive
      proliferative capacity as evidenced by their ability to continuously grow even
      when seeded at low dilutions. The morphologic features and normal differentiation
      patterns seen in normal OSE cells were likewise retained by the hTERT-transfected
      cells. In addition, the cultures remained responsive to physiologic
      concentrations of epidermal growth factor and transforming growth factor-beta.
      Changes associated with neoplastic transformation like anchorage-independent
      growth, tumorigencity and karyotypic instability were not observed. CONCLUSIONS:
      We were able to show that the ectopic expression of hTERT in normal human OSE: 1)
      resulted in cultures with greater growth potential and longer lifespan and 2) did
      not induce a transformed phenotype previously seen in viral oncogene-transfected
      OSE cells. The established cell lines would not only provide sufficient material
      for comprehensive studies to investigate the normal physiology of OSE cells, but
      could also help in the understanding of the early steps of ovarian
      carcinogenesis.

PMID- 15582502
TI  - Society of Gynecologic Investigation: what gets published?
AB  - OBJECTIVE: To compare publication rates of the plenary slide presentations
      (plenary), concurrent slide presentations (concurrent), and poster presentations
      (poster) at Society for Gynecologic Investigation (SGI) meetings for the interval
      1990 to 1999. METHODS: The SGI program and abstract books for years 1990-1999
      were examined, with all plenary and twice the number of randomly selected
      concurrent and poster abstracts identified. For each abstract, PUBMED was used to
      search for authors and subject topics, if needed. Rates of publication in various
      journals were compared: group 1: weekly general journals (New England Journal of
      Medicine [NEJM], Journal of the American Medical Association [JAMA], Nature);
      group 2: monthly obstetrics/gynecology journals (American Journal of Obstetrics
      and Gynecology, Obstetrics and Gynecology); and group 3: other journals
      (Placenta, Journal of Maternal Fetal Medicine, Fertility and Sterility, etc).
      Factors predicting ultimate publication were assessed by multivariable analysis.
      RESULTS: Over the 10-year period, 75% of the plenary, 75% of the concurrent, and
      66% of the poster abstract presentations were published (P = not significant
      [NS]), with the majority being published in group 3 journals. Multivariable
      analysis did not find any factor predictive of publication in plenary,
      concurrent, or poster groups. Sixty-five percent of all presentations were basic
      science-related and this did not change over time. CONCLUSIONS: SGI presentations
      have an overall publication rate of 68%, which is higher than that reported in
      the literature for other societies (29-45%). Furthermore, the plenary and
      concurrent publication rates were not different from the poster publication rate.
      This suggests that all types of presentations are of quality as measured by
      publication rate. The SGI continues to publish predominantly basic science
      research, which is one of its missions.

PMID- 15582503
TI  - Soluble Fas concentrations in the follicular fluid and oocyte-cumulus complex
      culture medium from women undergoing in vitro fertilization: association with
      oocyte maturity, fertilization, and embryo quality.
AB  - OBJECTIVE: Because soluble Fas (sFas) inhibits Fas-mediated apoptosis by
      preventing death signal transduction, we determined sFas concentrations in the
      follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) from women
      undergoing in vitro fertilization (IVF) in order to associate its concentrations
      with oocyte maturity, fertilization, and embryo quality. METHODS: We studied 82
      follicles from 11 healthy women (mean age, 35.4 +/- 3.8 years) using a long
      protocol for IVF treatment. Individual FF and matched CM samples were immediately
      centrifuged at 4C and sFas concentrations were determined by sandwich enzyme
      linked immunosorbent assays. RESULTS: sFas concentrations were significantly
      higher in FF than in CM (P <.0001) and when oocytes were mature rather than
      immature (P <.002). Of 70 mature and 12 immature oocytes, 56 (80%) and two
      (16.6%), respectively, were fertilized. sFas concentrations in CM were
      significantly lower when mature oocytes were fertilized versus nonfertilized (P
      <.005). sFas concentrations in FF and CM were significantly related in an inverse
      manner to embryo quality (P = .004 and P = .0002, respectively). CONCLUSION: FF
      and CM from women undergoing IVF contain sFas. The latter has anti-apoptotic
      properties and levels are higher: in FF when oocytes are mature and in CM when
      oocytes are nonfertilized. Furthermore, FF and CM sFas concentrations are
      negatively correlated with embryo quality.

PMID- 15582504
TI  - Identification and characterization of an interspersed repetitive DNA fragment in
      Plasmodium vivax with potential use for specific parasite detection.
AB  - We cloned and characterized a Plasmodium vivax repeat element of 7872bp named
      PvRE7.8. Several internal tandem repeats were found along the sequence. The
      repetitive nature of the PvRE7.8 element was confirmed by hybridization of a P.
      vivax YAC library. Based on the data bank analysis and the presence of two
      contiguous putative genes that may encode proteins related to DNA metabolism,
      PvRE7.8 could be considered an inactivated transposon-LINE element. By using Pv79
      as probe or primers derived from Pv79-flanking sequences, P. vivax DNA Could be
      detected from whole blood and mosquito samples. We consider that the repeat
      element described here has potential for P. vivax malaria diagnosis and for
      epidemiological analysis of P. vivax transmission areas.

PMID- 15582505
TI  - Entamoeba histolytica: correlation of assessment methods to measure erythrocyte
      digestion, and effect of cysteine proteinases inhibitors in HM-1:IMSS and HK
      9:NIH strains.
AB  - Entamoeba histolytica trophozoites are able to degrade human erythrocytes; the
      loss of erythrocyte cellular matrix and degradation of plasma membrane were
      observed, along with the decrease in the average size of digestive vacuoles.
      Ninety-six percent of hemoglobin ingested was hydrolyzed by trophozoites within
      3h, as evidenced by electrophoresis. Accordingly, X-ray spectroscopy revealed the
      presence of iron inside vacuoles after erythrophagocytosis, the concentration of
      which decreased to control levels in a similar period. Quantification of
      erythrocyte digestion at the early and late periods was determined by a
      spectrophotometric procedure, with t(1/2)=1.67 h and 35-min for HM-1:IMSS and HK
      9:NIH trophozoites, respectively. In the latter, activity was due to the combined
      action of intracellular enzymatic activity and exocytosis. E-64c and leupeptin
      totally inhibited erythrocyte digestion within a 3-h period, thereafter
      hydrolysis took place at lower rate. Our results suggest that erythrocyte
      digestion in E. histolytica proceeds in different ways in these two amebic
      strains, and can be blocked by proteinase inhibitors.

PMID- 15582506
TI  - Trichinella spiralis: stimulation of mast cells by TSL-1 antigens trigger
      cytokine mRNA expression and release of IL-4 and TNF through an Ig-independent
      pathway.
AB  - Previous in vitro studies have demonstrated that mast cells (MC) can be directly
      activated by Trichinella spiralis larvae 1 (TSL-1) antigens. To characterize even
      more this activation of MC and their possible role on induction and regulation of
      the Type 2 response generated against T. spiralis infection, we studied the
      interaction between a hybrid rat MC line (HRMC), murine bone marrow MC (mBMMC),
      and TSL-1 antigens. Immunofluorescence staining and flow cytometry analysis
      showed that TSL-1 antigens bound to the surface of HRMC cells, resulting in the
      transcriptional induction and in the release of TNF and IL-4. Besides, an
      increase of IL-4 intracellular expression was also observed in mBMMC. This
      suggests that MC may play an important role in the early immune response against
      T. spiralis and may be a source of cytokines, that regulate the final onset of
      the immune mechanisms which determine the course of the infection.

PMID- 15582507
TI  - Specificity of modified Drosophila mariner transposons in the identification of
      Leishmania genes.
AB  - Genetic manipulation of the protozoan Leishmania has led to a better
      understanding of the survival and development of these pathogens within their
      hosts. The association of the Leishmania genome sequencing information with the
      ability of transposons to introduce or destroy phenotypes allows a global
      perspective on the role and importance of genes in cellular pathways. Herein we
      report the construction and testing of mariner transposable elements carrying the
      neomycin phosphotransferase, green fluorescent protein, or beta-glucuronidase
      genes as reporters for translational fusion events. We demonstrate that the
      expression of the reporter genes will occur only when the genes are inserted in
      frame within predicted genes. Our results not only add to the mariner toolkit for
      gene manipulation but also strengthen the evidence that the mariner system is a
      reliable means for the study of gene expression in Leishmania.

PMID- 15582508
TI  - Plasmodium falciparum: sequence diversity and antibody recognition of the
      Merozoite surface protein-2 (MSP-2) in Brazilian Amazonia.
AB  - The merozoite surface protein-2 (MSP-2) of Plasmodium falciparum comprises
      repeats flanked by dimorphic domains defining the allelic families FC27 and IC1.
      Here, we examined sequence diversity at the msp-2 locus in Brazil and its impact
      on MSP-2 antibody recognition by local patients. Only 25 unique partial sequences
      of msp-2 were found in 61 isolates examined. The finding of identical msp-2
      sequences in unrelated parasites, collected 6-13 years apart, suggests that no
      major directional selection is exerted by variant-specific immunity in this
      malaria-endemic area. To examine antibody cross-reactivity, recombinant
      polypeptides derived from locally prevalent and foreign MSP-2 variants were used
      in ELISA. Foreign IC1-type variants, such as 3D7 (currently tested for human
      vaccination), were less frequently recognized than FC27-type and local IC1-type
      variants. Antibodies discriminated between local and foreign IC1-type variants,
      but cross-recognized structurally different local IC1-type variants. The use of
      evolutionary models of MSP-2 is suggested to design vaccines that minimize
      differences between local parasites and vaccine antigens.

PMID- 15582509
TI  - Trypanosomatid flagellum biogenesis: ARL-3A is involved in several species.
AB  - Overexpression in Leishmania amazonensis promastigotes of the GTPase-deficient
      small G protein LdARL-3A-Q70L specifically provokes the loss of the flagella
      without affecting cell viability and body size. However, motility is lost and,
      remarkably, cells do not survive in the insect vector Lutzomyia longipalpis gut,
      leading to interruption of parasite transmission. We report here that
      overexpression of the same protein in Leishmania major, Leishmania donovani, and
      Crithidia fasciculata also led to significant alterations of the flagella.
      Surprisingly, ablation of TbARL-3A expression by RNAi in Trypanosoma brucei
      brucei also provoked flagella shortening, revealing that overexpression of the
      GTPase-deficient protein seems functionally equivalent to a drastic reduction in
      its native counterpart abundance. This renders possible complementary studies of
      an essential pathway in related organisms. Potential significance for the protein
      function is discussed as well as future strategies for stopping the transmission
      of several neglected parasitic diseases.

PMID- 15582510
TI  - Comparison of pathology in susceptible A/J and resistant C57BL/6J mice after
      infection with different sub-strains of Plasmodium chabaudi.
AB  - Susceptible A/J and more resistant C57BL/6J mice were infected with Plasmodium
      chabaudi chabaudi 54X, P.c. chabaudi AS and Plasmodium chabaudi adami 408XZ. As
      expected, most C57BL/6J mice survived the infections with the different isolates.
      But in contrast to previous observations, not all A/J mice succumbed to
      infection: just over 50% of A/J mice survived infections with P.c. chabaudi 54X,
      while 80% survived P.c. chabaudi AS. The more virulent parasite, P.c. adami
      408XZ, was able to kill all A/J mice and 20% of C57BL/6J mice after an
      intravenous infection with 10(5) pRBC. A detailed study of four parameters of
      pathology (body weight, body temperature, blood glucose and RBC counts) in both
      mouse strains after a P.c. adami 408XZ infection showed similar patterns to those
      previously reported after infection with P.c. chabaudi AS. These data suggest
      that environmental factors as well as parasite polymorphisms might influence the
      severity of malaria between susceptible and resistant mice.

PMID- 15582511
TI  - Intestinal DNases of 36 and 38.5kDa from the parasitic nematode Haemonchus
      contortus have non-classic DNase characteristics and produce DNA fragments with
      3'-hydroxyls.
AB  - Treatment with the anthelmintic fenbendazole induces fragmentation of genomic DNA
      in intestinal cells of Haemonchus contortus. This effect is characterized by DNA
      fragments with 3'-hydroxyls (OH). Investigation into DNases responsible
      identified intestinal DNase activities that produce DNA fragments with 3'-OH.
      However, this interpretation was complicated by a mixture of activities in the
      intestinal fractions evaluated. In addition, intestinal activities displayed non
      classic characteristics. Here it is shown that heparin sulfate (HS) fractionation
      enriched for intestinal DNases that produce 3'-OH. The 2.0M NaCl fraction of HS
      contained DNase activity that produced 3'-OH with minimal contamination by
      activity that produced 3'-phosphates (P). 3'-OH were produced under acidic (pH
      5.0) or neutral (pH 7.0) conditions by DNases in this fraction. These DNases were
      sensitive to EDTA under each condition. Furthermore, EDTA-sensitive DNase
      activity in this fraction digested H. contortus intestinal cell nuclear DNA in
      histological sections, producing 3'-OH under acidic and neutral conditions.
      DNases at 36 and 38.5kDa in this fraction each produced 3'-OH at pH 5.0 when gel
      eluted, and each activity was sensitive to EDTA. Hence, the 36 and 38.5kDa DNases
      in the 2.0M NaCl HS intestinal fraction have characteristics expected for
      candidate DNases that mediate DF in H. contortus intestinal cell nuclei induced
      by fenbendazole. DNase activity that produces 3'-OH under acidic condition with
      sensitivity to EDTA is unconventional for classic acidic or neutral DNases and is
      a unique finding for nematodes. Excretory/secretory products from the worm and
      whole worm lysates were also explored as sources to fractionate intestinal DNases
      identified. HS fractionation of those worm samples did not clearly resolve the
      intestinal DNases of interest, although DNases with distinct characteristics were
      identified in each source.

PMID- 15582512
TI  - The caudal complex of Giardia lamblia and its relation to motility.
AB  - This paper presents a detailed study of the caudal complex of Giardia lamblia and
      its relation to movements observed in this region. The caudal complex of Giardia,
      composed of axonemes from the caudal flagella plus associated microtubular
      sheets, was investigated by light, electron microscopy, and 3D reconstruction
      tools. By the use of video-microscopy and digital image processing techniques, we
      were able to visualize in detail the caudal movements. A non-ionic detergent,
      Triton X-100, was used to isolate the complex that was afterwards analyzed by
      video-microscopy and transmission electron microscopy (TEM). We showed for the
      first time, using video-microscopy, that the intracellular portion of the caudal
      flagella axonemes presented motility, even after the disrupture of the cell
      membrane, contrasting with the caudal flagella themselves, that do not show
      active beating pattern. To check if actin filaments play a role in the above
      described movements, as previously supposed, we incubated the cells with
      jasplakinolide, a drug that induces the disruption of actin filaments in living
      cells. The experiments demonstrated that the drug did not affect the caudal
      motility. The analysis of the caudal complex by transmission electron microscopy
      (TEM) revealed that, even after the exposure to higher detergent concentrations,
      the connections between their components remained intact. The information
      obtained by TEM and 3D reconstruction tools showed that the region between both
      nuclei marks the intracellular end of the caudal complex, which proceeds toward
      the caudal portion of the cell following its longitudinal axis, where the
      axonemes emerge as the caudal flagella. The results obtained from video
      microscopy assays of the isolated beating complex together with the 3D
      reconstruction data indicated that the internal portion of the caudal flagella is
      the force-generator of the movements in this region.

PMID- 15582513
TI  - In vitro inhibition of beta-haematin formation, DNA interactions, antiplasmodial
      activity, and cytotoxicity of synthetic neocryptolepine derivatives.
AB  - Neocryptolepine, a minor alkaloid of Cryptolepis sanguinolenta, was investigated
      as a lead for new antiplasmodial agents, because of its lower cytotoxicity than
      cryptolepine, the major alkaloid. Synthetic 2- or 3-substituted neocryptolepine
      derivatives were evaluated for their biological activity. In addition to the
      antiplasmodial activity (Plasmodium falciparum chloroquine-sensitive and 
      resistant) also the cytotoxicity (MRC-5 cells) was determined. Several compounds
      such as 2-bromoneocryptolepine showing higher and more selective antiplasmodial
      activity than neocryptolepine were obtained. Several functional assays and in
      vitro tests were used to obtain additional information on the mechanism of
      action, i.e., the beta-haematin formation inhibitory assay (detoxification of
      haem) and the DNA-methylgreen displacement assay (interaction with DNA). It could
      be demonstrated that the 2- or 3-substituted neocryptolepine derivatives
      investigated here have about the same potency to inhibit the beta-haematin
      formation as chloroquine, indicating that inhibition of haemozoin formation makes
      at least an important contribution to their antiplasmodial activity, although
      their in vitro antiplasmodial activity is still less than chloroquine.

PMID- 15582514
TI  - Mesocestoides corti: a LIM-homeobox gene upregulated during strobilar
      development.
AB  - To understand the molecular processes regulating morphological changes during
      cestode life histories we focused on homeodomain (HD) proteins, a family of
      transcription factors essential for pattern formation during development. In this
      study we report the isolation of the partial sequence of MvLim, a LIM-HD gene of
      Mesocestoides corti. Other members of this gene family, characterized in
      Drosophila melanogaster, Caenorhabditis elegans and vertebrates contribute to
      cell fate determination of various neuronal subtypes. Phylogenetic analyses
      showed that MvLim clusters with members of the LIN-11 group and that
      platyhelminths have at least two different LIM-HD genes. By real time PCR we
      determined that MvLim expression is 20-fold greater in segmented worms than in
      tetrathyridia. The enhancement of MvLim expression during strobilation could be
      associated to changes in the innervation pattern occurring in proglottids
      development.

PMID- 15582515
TI  - Trypanosoma cruzi: productive infection is not allowed by chorionic villous
      explant from normal human placenta in vitro.
AB  - We hypothesize that a sustained infection of Trypanosoma cruzi into placental
      tissue might be diminished. Human placental chorionic villi and VERO cells as
      controls were co-cultured with T. cruzi. Parasites occupied 0.0137% at 3h,
      0.0224% (24h), and 0.0572% (72 h) of the total chorionic villi area analyzed and
      some few placental samples were negative to parasite DNA, whereas 52% of VERO
      cells were infected at 3h and parasites occupied 0.57%, at 24h the parasite area
      was of 2.78% and at 72 h was of 3.32%. There were no live parasites in placenta
      T. cruzi culture media at 72 h of co-culture. There were significantly increased
      dead parasites when T. cruzi was treated with unheated culture media coming from
      placental explants and fewer dead parasites when pre-heated culture media were
      employed. CONCLUSION: Low productive infection by T. cruzi into placental tissue
      associated with no viable parasites in the culture media partially due to
      placental thermo labile substances.

PMID- 15582516
TI  - Dirofilaria immitis: identification of a novel ligand-gated ion channel-related
      polypeptide.
AB  - We have isolated a cDNA from Dirofilaria immitis that encodes a predicted ion
      channel subunit, Di-LGR-1. Secondary structure predictions and database searches
      reveal that Di-LGR-1 is distantly related to ligand-gated anion channels, such as
      the GABA(A) receptors, though there are marked differences in the sequences of
      the putative channel forming regions. Di-LGR-1 has 52% sequence identity to the
      Caenorhabditis elegans predicted polypeptide, T27A1.4: neighbour-joining trees
      show that these two polypeptides are the most divergent members of the nematode
      ligand-gated anion channel family. No close homologues are present in
      vertebrates, suggesting that their function may be specific to nematodes. RNAi
      experiments using a fragment of T27A1.4 with C. elegans failed to reveal any
      obvious phenotype, so the function of these channels remains unknown.

PMID- 15582517
TI  - The alanine-rich heptad repeats are intact in the processed form of Plasmodium
      falciparum MSP3.
AB  - The potential of Plasmodium falciparum merozoite surface protein 3 as a component
      of an asexual-stage malaria vaccine is currently being assessed. The precursor
      form of MSP3 undergoes cleavage during schizogony to generate a mature processed
      form. It is unknown if this cleavage event is necessary for MSP3 function, but it
      may be an important consideration for assessing and developing MSP3 as an asexual
      stage vaccine candidate. We have therefore determined the cleavage site in MSP3
      by sequencing the N-terminus of the processed form of MSP3, which was isolated
      from parasite material. The position of the cleavage site indicates that the
      processed form of MSP3 retains the three blocks of alanine-rich heptad repeats,
      which are predicted to provide the structural framework for an intramolecular
      coiled-coil. The cleavage-site motif has many features in common with the
      published cleavage sites of MSP1(30), MSP6(36), and MSP7(22), which are all
      located on the merozoite surface and are implicated in the erythrocyte invasion
      process. The common cellular location and similar cleavage-site motifs suggest
      that these merozoite proteins may be cleaved by the same or related proteases.

PMID- 15582518
TI  - Malaria: A Grand Challenge. Proceedings of a Johns Hopkins Research Institute
      Meeting. 25-26 March 2004, Baltimore, Maryland, USA.

PMID- 15582519
TI  - Parasite ligand-host receptor interactions during invasion of erythrocytes by
      Plasmodium merozoites.
AB  - Malaria parasites must recognise and invade different cells during their life
      cycle. The efficiency with which Plasmodium falciparum invades erythrocytes of
      all ages is an important virulence factor, since the ability of the parasite to
      reach high levels of parasitemia is often associated with severe pathology and
      morbidity. The merozoite invasion of erythrocytes is a highly complex, multi-step
      process that is dependent on a cascade of specific molecular interactions.
      Although many proteins are known to play an important role in invasion, their
      functional characteristics remain unclear. Therefore, a complete understanding of
      the molecular interactions that are the basis of the invasion process is
      absolutely crucial, not only in improving our knowledge about the basic biology
      of the malarial parasite, but also for the development of intervention strategies
      to counter the disease. Here we review the current state of knowledge about the
      receptor-ligand interactions that mediate merozoite invasion of erythrocytes.

PMID- 15582520
TI  - Gene expression in Plasmodium: from gametocytes to sporozoites.
AB  - Completion of the complex developmental program of Plasmodium in the mosquito is
      essential for parasite transmission, yet this part of its life cycle is still
      poorly understood. In recent years, considerable progress has been made in the
      identification and characterization of genes expressed during parasite
      development in the mosquito. This line of investigation was greatly facilitated
      by the availability of the genome sequence of several Plasmodium, and by the
      application of approaches such as proteomics, microarrays, gene disruption by
      homologous recombination (gene knockout) and by use of subtraction libraries.
      Here, we review what is presently known about genes expressed in gametocytes and
      during the Plasmodium life cycle in the mosquito.

PMID- 15582521
TI  - A proteomic analysis of malaria biology: integration of old literature and new
      technologies.
AB  - The genomic revolution has brought a new vitality into research on Plasmodium,
      its insect and vertebrate hosts. At the cellular level nowhere is the impact
      greater than in the analysis of protein expression and the 'assembly' of the
      supramolecular machines that together comprise the functional cell. The
      repetitive phases of invasion and replication that typify the malaria life cycle,
      together with the unique phase of sexual differentiation provide a powerful
      platform on which to investigate the 'molecular machines' that underpin parasite
      strategy and stage-specific functions. This approach is illustrated here in an
      analysis of the ookinete of Plasmodium berghei. Such analyses are useful only if
      conducted with a secure understanding of parasite biology. The importance of
      carefully searching the older literature to reach this understanding cannot be
      over-emphasised. When viewed together, the old and new data can give rapid and
      penetrating insights into what some might now term the 'Systems-Biology' of
      Plasmodium.

PMID- 15582522
TI  - Molecular complexity of sexual development and gene regulation in Plasmodium
      falciparum.
AB  - The malaria parasite, Plasmodium falciparum, has a complex life cycle which
      alternates between the vertebrate host and the invertebrate vector. Various
      morphological changes as well as stage-specific transcripts and gene expression
      profiles that accompany parasite's asexual and sexual life cycle suggest that
      gene regulation is crucial for the parasite's continual adaptations to survive
      the changing environments as well as for pathogenesis. Development of sexual
      stages is crucial for malaria transmission and relatively little is known about
      the role of specific gene products during asexual to sexual differentiation and
      further development. Therefore, in order to have a full understanding of the
      biology of the malaria parasite, gene regulation on a genome-wide global level
      must be understood, an area remaining to be elucidated in P. falciparum. Parasite
      features, such as A-T bias, difficulties in cloning, labor-intensive culture and
      purification of specific stages of the parasite, all contribute to the
      difficulties to investigate many aspects of parasite biology. However, despite
      these challenges, limited studies have revealed a number of parallelisms with
      eukaryotic transcription. For example, the parasite's genes are organised in a
      similar fashion, contain promoter elements and upstream activation sequences, as
      shown by structural searches and functional assays, and some of the basal
      machinery and general transcription factors have been found in Plasmodium. The
      completion of the full genome sequence of P. falciparum and other species of
      Plasmodium has resulted in the search for specific transcription factors through
      genome mining. Although genome mining may identify some of the factors, search
      for these factors solely by primary sequence homology would result in a non
      comprehensive list for transcription factors present in the genome. Here, we
      present further discussion on putative transcription factors like activities
      detected in the asexual and sexual stages of P. falciparum.

PMID- 15582523
TI  - The role of programmed cell death in Plasmodium-mosquito interactions.
AB  - Many host-parasite interactions are regulated in part by the programmed cell
      death of host cells or the parasite. Here we review evidence suggesting that
      programmed cell death occurs during the early stages of the development of the
      malaria parasite in its vector. Zygotes and ookinetes of Plasmodium berghei have
      been shown to die by programmed cell death (apoptosis) in the midgut lumen of the
      vector Anopheles stephensi, or whilst developing in vitro. Several morphological
      markers, indicative of apoptosis, are described and evidence for the involvement
      of a biochemical pathway involving cysteine proteases discussed in relationship
      to other protozoan parasites. Malaria infection induces apoptosis in the cells of
      two mosquito tissues, the midgut and the follicular epithelium. Observations on
      cell death in both these tissues are reviewed including the role of caspases as
      effector molecules and the rescue of resorbing follicles resulting from
      inhibition of caspases. Putative signal molecules that might induce parasite and
      vector apoptosis are suggested including nitric oxide, reactive nitrogen
      intermediates, oxygen radicals and endocrine balances. Finally, we suggest that
      programmed cell death may play a critical role in regulation of infection by the
      parasite and the host, and contribute to the success or not of parasite
      establishment and host survival.

PMID- 15582524
TI  - The Plasmodium parasite--a 'new' challenge for insect innate immunity.
AB  - Though lacking adaptive immunity, insects possess a powerful innate immune
      system, a genome-encoded defence machinery used to confront infections. Studies
      in the fruit fly Drosophila melanogaster revealed a remarkable capacity of the
      innate immune system to differentiate between and subsequently respond to
      different bacteria and fungi. However, hematophagous compared to non
      hematophagous insects encounter additional blood-borne infectious agents, such as
      parasites and viruses, during their lifetime. Anopheles mosquitoes become
      infected with the malaria parasite Plasmodium during feeding on infected human
      hosts and may then transmit the parasite to new hosts during subsequent bites.
      Whether Anopheles has developed mechanisms to confront these infections is the
      subject of this review. Initially, we review our current understanding of innate
      immune reactions and give an overview of the Anopheles immune system as revealed
      through comparative genomic analyses. Then, we examine and discuss the capacity
      of mosquitoes to recognize and respond to infections, especially to Plasmodium,
      and finally, we explore approaches to investigate and potentially utilize the
      vector immune competence to prevent pathogen transmission. Such approaches
      constitute a new challenge for insect immunity research, a challenge for global
      health.

PMID- 15582525
TI  - Plasmodium falciparum transmission rate and selection for drug resistance: a
      vexed association or a key to successful control?
AB  - While malaria eradication campaigns once adopted a combination of vector control
      and chemotherapy to overcome the disease, today's opinion on the matter is
      equivocal. So what has changed? This paper reviews some of the confusing
      hypotheses on the relationship between Plasmodium falciparum transmission and
      levels of drug resistance. New field evidence showing variations of in vivo
      chloroquine resistance in relation to indoor residual spraying and natural
      endemicity patterns, is considered with a view to how these phenomena implicate
      on control.

PMID- 15582526
TI  - Cysteine proteases of malaria parasites.
AB  - A number of cysteine proteases of malaria parasites have been described, and many
      more putative cysteine proteases are suggested by analysis of the Plasmodium
      falciparum genome sequence. Studies with protease inhibitors have suggested roles
      for cysteine proteases in hemoglobin hydrolysis, erythrocyte rupture, and
      erythrocyte invasion by erythrocytic malaria parasites. The best characterised
      Plasmodium cysteine proteases are the falcipains, a family of papain-family (clan
      CA) enzymes. Falcipain-2 and falcipain-3 are hemoglobinases that appear to
      hydrolyse host erythrocyte hemoglobin in the parasite food vacuole. This function
      was recently confirmed for falcipain-2, with the demonstration that disruption of
      the falcipain-2 gene led to a transient block in hemoglobin hydrolysis. A role
      for falcipain-1 in erythrocyte invasion was recently suggested, but disruption of
      the falcipain-1 gene did not alter parasite development. Other papain-family
      proteases predicted by the genome sequence include dipeptidyl peptidases, a
      calpain homolog, and serine-repeat antigens. The serine-repeat antigens have
      cysteine protease motifs, but in some the active site Cys is replaced by a Ser.
      One of these proteins, SERA-5, was recently shown to have serine protease
      activity. As SERA-5 and some other serine-repeat antigens localise to the
      parasitophorous vacuole in mature parasites, they may play a role in erythrocyte
      rupture. The P. falciparum genome sequence also predicts more distantly related
      (clan CD and CE) cysteine proteases, but biochemical characterisation of these
      proteins has not been done. New drugs for malaria are greatly needed, and
      cysteine proteases may provide useful new drug targets. Cysteine protease
      inhibitors have demonstrated potent antimalarial effects, and the optimisation
      and testing of falcipain inhibitor antimalarials is underway.

PMID- 15582527
TI  - Malarial anaemia: mechanisms and implications of insufficient erythropoiesis
      during blood-stage malaria.
AB  - It has been proposed that the basis of severe malarial anaemia, a major cause of
      morbidity and mortality in endemic areas, is multifactorial. Inappropriately low
      reticulocytosis is observed in malaria patients suggesting that insufficient
      erythropoiesis is a major factor. Clinical studies provide conflicting data
      concerning the production of adequate levels of erythropoietin (EPO) during
      malaria. Plasmodium chabaudi AS causes non-lethal infection in resistant C57BL/6
      mice, and lethal infection in susceptible A/J mice. In P. chabaudi AS infected
      C57BL/6 and A/J mice, which experience varying degrees of severity of anaemia,
      kidney EPO production is appropriate to the severity of anaemia and is regulated
      by haematocrit level. Neutralisation of endogenous EPO during infection leads to
      lethal anaemia while timely administration of exogenous EPO rescues mice although
      reticulocytosis is suppressed in proportion to the parasitemia level.
      Characterisation of alterations in splenic erythroid compartments in naive and P.
      chabaudi AS infected A/J mice revealed that infection, with or without EPO
      treatment, leads to sub-optimal increases in TER119+ erythroblasts compared to
      EPO-treated naive mice. A lower percentage of TER119+ erythroblasts in infected
      mice undergo terminal differentiation to become mature haemoglobin-producing
      cells. Furthermore, there is a shift in transferrin receptor (CD71) expression
      from TER119+ cells to a non-erythroid population. Deficiencies in the number and
      maturation of TER119+ erythroblasts during infection coincide with blunted
      proliferation to EPO stimulation in vitro by splenocytes, although a high
      frequency express EPO receptor (EPOR). Together, these data suggest that during
      malaria, EPO-induced proliferation of early EPOR+ erythroid progenitors is
      suppressed, leading to sub-optimal generation of TER119+ erythroblasts. Moreover,
      a shift in CD71 expression may result in impaired terminal maturation of
      erythroblasts. Thus, suppressed proliferation, differentiation, and maturation of
      erythroid precursors in association with inadequate reticulocytosis may be the
      basis of insufficient erythropoiesis during malaria.

PMID- 15582528
TI  - Natural killer cells and innate immunity to protozoan pathogens.
AB  - Natural killer (NK) cells are lymphoid cells that mediate significant cytotoxic
      activity and produce high levels of pro-inflammatory cytokines in response to
      infection. During viral infection, NK cell cytotoxicity and cytokine production
      is induced principally by monocyte-macrophage- and dendritic cell-derived
      cytokines but virally encoded ligands for NK cells are also beginning to be
      described. NK derived interferon-gamma (IFN-gamma) production is also essential
      for control of several protozoal infections including toxoplasmosis,
      trypanosomiasis, leishmaniasis and malaria. The activation of NK cells by
      protozoan pathogens is also believed to be cytokine-mediated although some recent
      studies suggest that direct recognition of parasites by NK cells also occurs.
      Both indirect signalling via accessory cell-derived cytokines and direct
      signalling, presumably through NK receptors, are needed in order for human
      malaria parasites (Plasmodium falciparum) to optimally stimulate NK activity.

PMID- 15582529
TI  - Regulation of the CD8+ T cell responses against Plasmodium liver stages in mice.
AB  - CD8+ T cells induced by immunization with Plasmodium sporozoites play a major
      role in protective immunity against parasite infection, inhibiting the
      development of liver stages. The activation of these T cells is initiated just a
      few hours after exposure to parasites and progresses rapidly through a tightly
      regulated program. Effector functions in CD8+ T are detectable as early as 24 h
      after immunization and this event is followed 24-48 h later by an accelerated
      expansion of the CD8+ T cell numbers which reaches a peak 4-5 days after priming.
      Concomitantly with the development of anti-parasite activity, CD8+ T cells
      acquire a self-regulatory role limiting the magnitude of the CD8+ T cell
      response. Once activated, CD8+ T cells strongly inhibit the priming of additional
      naive CD8+ T cells by competing for antigen presenting cells. On days 6-8 after
      immunization, a sudden contraction of this T cell response occurs due to
      programmed cell death of 70-80% of the activated cells. After this contraction
      phase, 15-20 days after priming, activated cells establish memory populations.
      The development and maintenance of these memory populations strictly depends on
      the presence of CD4+ T cells and IL-4, and probably also IL-7, IL-15 and IL-2.
      These cytokines, some of which are produced by CD4+ T cells, provide signals to
      prevents apoptosis and also induce the differentiation of memory sub-populations,
      most of which acquire definitive phenotypes 20-30 days after immunization.

PMID- 15582530
TI  - Use of long synthetic peptides to study the antigenicity and immunogenicity of
      the Plasmodium vivax circumsporozoite protein.
AB  - Three long synthetic peptides corresponding to amino (N), repeat (R) and carboxyl
      (C) regions of the Plasmodium vivax circumsporozoite (CS) protein were
      synthesised and used to assess their potential as vaccine candidates.
      Antigenicity studies were carried out using human blood samples from residents of
      a malaria-endemic area of Colombia, and immunogenicity was tested in Aotus
      monkeys. The N and C peptides spanned the total native amino and carboxyl
      flanking regions, whereas the R peptide corresponded to a construct based on the
      first central nona-peptide repeated in tandem three times and colinearly linked
      to a universal T-cell epitope (ptt-30) derived from tetanus toxin. All three
      peptides had been shown previously to contain several B-, T-helper (Th) and
      Cytotoxic T Lymphocytes (CTL) epitopes. Sixty-one percent of the human sera
      reacted with the R region, whereas 35 and 39% of the samples had antibodies
      against the N and C peptides, respectively. Human Peripheral Blood Mononuclear
      Cells (PBMC) showed higher levels of IFN-gamma than IL-4 when stimulated with
      peptides containing Th epitopes. Aotus monkeys immunised with the peptides
      formulated in either Montanide ISA720 or Freund's adjuvants produced strong
      antibody responses that recognised the peptide immunogens and the native
      circumsporozoite protein on sporozoites. Additionally, high IFN-gamma production
      was induced when Aotus lymphocytes were stimulated in vitro with each of the
      three peptides. We observed boosting of antibody responses and IFN-gamma
      production by exposure to live sporozoites. These results confirm the high
      antigenicity and immunogenicity of such synthetic polypeptides and underline
      their vaccine potential.

PMID- 15582531
TI  - Variant genes and the spleen in Plasmodium vivax malaria.
AB  - It is generally accepted that Plasmodium vivax, the most widely distributed human
      malaria, does not cytoadhere in the deep capillaries of inner organs and thus
      this malaria parasite must have evolved splenic evasion mechanism in addition to
      sequestration. The spleen is a uniquely adapted lymphoid organ whose central
      function is the selective clearance of cell and other particles from the blood,
      and microbes including malaria. Splenomegaly is a hallmark of malaria and no
      other disease seems to exacerbate this organ as this disease does. Besides this
      major selective clearance function however, the spleen is also an erythropoietic
      organ which, under stress conditions, can be responsible for close to 40% of the
      RBC populations. Data obtained in experimental infections of human patients with
      P. vivax showed that anaemia is associated with acute and chronic infections and
      it has been postulated that the continued parasitemia might have been sufficient
      to infect and destroy most circulating reticulocytes. We review here the basis of
      our current knowledge of variant genes in P. vivax and the structure and function
      of the spleen during malaria. Based on this data, we propose that P. vivax
      specifically adhere to barrier cells in the human spleen allowing the parasite to
      escape spleen-clearance while favouring the release of merozoites in an
      environment where reticulocytes, the predominant, if not exclusive, host cell of
      P. vivax, are stored before their release into circulation to compensate for the
      anaemia associated with vivax malaria.

PMID- 15582532
TI  - Treatment with 17-beta-estradiol reduces superoxide production in aorta of
      ovariectomized rats.
AB  - OBJECTIVE: Oxidant stress contributes to vascular injury and atherosclerosis. We
      hypothesized that estrogen treatment of ovariectomized rats decreases O(2)(-) by
      decreasing the activity of NAD(P)H oxidase and this reduction in O(2)(-) could
      have a vasculoprotective effect. METHODS AND RESULTS: Ovariectomized rats were
      treated with 17-beta-estradiol E2 (0.25mg) or oil placebo for 21 days. Aorta were
      removed for contractility studies and O(2)(-) production was measured by
      lucigenin enhanced chemiluminescence (230 and 5microM). E2 treatment decreased
      basal O(2)(-) production but did not alter NADH or NADPH stimulated O(2)(-)
      production. Total p47phox and p47phox in membrane fractions of cardiac tissue
      were decreased, which suggests less activation of NAD(P)H oxidase in E2 treated
      rats. E2 did not change expression of other components of NAD(P)H oxidase in
      heart, lung, spleen and diaphragm. Expression of eNOS was also lower in E2
      treated rats. E2 did not affect the contractile response to phenylepherine,
      dilation with acetylcholine, dilation with superoxide dismutase or constriction
      with l-NAME. This argues against changes in bioavailable NO. CONCLUSIONS: E2
      decreases activation of p47phox and O(2)(-) production by NAD(P)H oxidase. This
      did not affect contractile properties of the vessel, but could still potentially
      alter cell signaling from oxidant increasing stresses.

PMID- 15582533
TI  - Clemmensen reduction of diosgenin and kryptogenin: synthesis of
      [16,16,22,22,23,23-(2)H(6)]-(25R)-26-hydroxycholesterol.
AB  - A new experimental protocol has been established for the Clemmensen reduction of
      diosgenin and kryptogenin with the aim to prepare deuterated isotopomers of (25R)
      26-hydroxycholesterol. Uncontrolled deuteration has been achieved from diosgenin,
      whereas [16,16,22,22,23,23-(2)H(6)]-(25R)-26-hydroxycholesterol (1) can be
      synthesized from kryptogenin.

PMID- 15582534
TI  - Characterization of a monoclonal antibody for human aldo-keto reductase AKR1C3
      (type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid
      dehydrogenase); immunohistochemical detection in breast and prostate.
AB  - Human aldo-keto reductase AKR1C3 (type 2 3alpha-hydroxysteroid dehydrogenase/type
      5 17beta-hydroxysteroid dehydrogenase) catalyzes the reduction of Delta(4)
      androstene-3,17-dione to yield testosterone, the reduction of 5alpha
      dihydrotestosterone to yield 3alpha- and 3beta-androstanediol, and the reduction
      of estrone to yield 17beta-estradiol. Relatively, high mRNA expression of AKR1C3
      was found in human prostate and mammary gland where it is implicated in
      regulating ligand access to the androgen and estrogen receptor, respectively.
      AKR1C3 shares high sequence identity >86% with related plastic human 20alpha
      hydroxysteroid dehydrogenases (AKR1C1), type 3 3alpha-hydroxysteroid
      dehydrogenase (AKR1C2) and type 1 3alpha-hydroxysteroid dehydrogenase (AKR1C4),
      and reagents are urgently needed to discriminate between these enzymes at the
      mRNA, protein and functional level. We describe the characterization of a high
      titer isoform specific monoclonal antibody (Ab) for AKR1C3. It does not cross
      react with human AKR1C1, AKR1C2 or AKR1C4, human aldehyde reductase AKR1A1 or rat
      3alpha-hydroxysteroid dehydrogenase (AKR1C9) on immunoblot analysis. The
      monoclonal Ab can be used to detect AKR1C3 expression by immunohistochemistry in
      sections of paraffin-embedded mammary gland and prostate. In the breast enzyme
      staining was detected in ductal carcinoma in situ where the cancerous cells were
      strongly immunoreactive. In normal prostate immunoreactivity was limited to
      stromal cells with only faint staining in the epithelial cells. In adenocarcinoma
      of the prostate elevated staining was observed in the endothelial cells and
      carcinoma cells. The reagent thus has utility to access the localized expression
      of AKR1C3 in hormonal dependent malignancies of the breast and prostate.

PMID- 15582535
TI  - Synthesis of polyhydroxysterols (V): efficient and stereospecific synthesis of 24
      methylene-cholest-5-ene-3beta,7alpha-diol and its C-7 epimer.
AB  - This paper describes the efficient and stereospecific synthesis of cytotoxic
      dihydroxylated sterols, 24-methylene-cholest-5-ene-3beta,7alpha-diol 1, and its C
      7 epimer, 24-methylene-cholest-5-ene-3beta,7beta-diol 2. The crux of the
      synthesis is that the selective allylic oxidation of 24-methylene-cholesteryl
      acetate proceeds to 24-methylene-7-keto-cholesteryl acetate without extensive
      byproduct formation from reaction at the Delta24(28) double bond. This
      methodology may be useful for the preparation of other oxysterols with non
      standard side chains.

PMID- 15582536
TI  - Phytoecdysteroids and glycoceramides from Eriophyton wallchii.
AB  - Two new compounds, 28-epi-cyasterone and eriophytonoide, along with 11 known
      compounds, cyasterone, ajuforrestins A and B, 20-hydroxyecdysone, polypodin B,
      ajugalactone, 8-O-acetylharpagid, apigenin, N-[2hydroxy-(nonadecanoyl
      tricosanoyl)]-4-hydroxy-trans-8-sphingenine, beta-sitosterol, and daucosterol,
      were isolated from the aqueous ethanolic extract of the whole herb of Eriophyton
      wallchii Benth. The structures of 28-epi-cyasterone and eriophytonoide were
      elucidated as (22R,24S,25S,28S)-5beta-stigmast-7-en-26-oic acid,
      2beta,3beta,14,20,22,28-hexa hydroxy-6-oxo-gamma-lactone, and 1-O-beta-d
      glucopyranosyl-(2S,3S,4R,8E)-2-[(2R)-2-hydroxyhexadecanoylamino]-1,3,4
      octadecanetriol-8-ene, respectively, on the basis of spectral and chemical
      evidence.

PMID- 15582537
TI  - Simultaneous determination of dehydroepiandrosterone and its 7-oxygenated
      metabolites in human serum by high-resolution gas chromatography--mass
      spectrometry.
AB  - A highly sensitive and specific method has been developed for the simultaneous
      measurement of free (unconjugated) or sulfate-conjugated forms of
      dehydroepiandrosterone (DHEA), 7alpha-hydroxy-DHEA (7alpha-OH-DHEA), 7beta
      hydroxy-DHEA (7beta-OH-DHEA), and 7-oxo-DHEA (7-oxo-DHEA) in human serum. This
      method is based upon a stable isotope-dilution technique by gas chromatography
      selected-ion monitoring mass spectrometry. Free steroids were extracted from
      serum with an organic solvent and the sulfate-conjugated steroids remained in
      aqueous phase. Free steroids were purified by solid-phase extraction, while
      sulfate-conjugated steroids were hydrolyzed by sulfatase and deconjugated
      steroids were purified by solid-phase extractions. The extracts were treated with
      O-methylhydroxylamine hydrochloride and were subsequently
      dimethylisopropylsilylated. The resulting methyloxime-dimethylisopropylsilyl (MO
      DMIPS) ether derivatives were quantified by gas chromatography-selected-ion
      monitoring mass spectrometry in a high-resolution mode. The detection limits of
      MO-DMIPS ether derivatives of DHEA, 7alpha-OH-DHEA, 7beta-OH-DHEA and 7-oxo-DHEA
      were 1.0, 0.5, 0.5 and 2.0pg, respectively. Coefficients of variation between
      samples ranged from 10.6 to 22.9% for free 7-oxygenated DHEA to less than 10% for
      DHEA and sulfate-conjugated 7-oxygenated DHEA. The concentrations of these
      steroids were measured in 18 sera samples from healthy volunteers (9 males and 9
      females; aged 23-78 years). Free DHEA, 7alpha-OH-DHEA, 7beta-OH-DHEA and 7-oxo
      DHEA levels ranged between 0.21-3.55, 0.001-0.194, 0.003-0.481, and 0.000
      0.077ng/ml, respectively, and the sulfate-conjugated steroid levels of these
      metabolites ranged between 253-4681, 0.082-3.001, 0.008-0.903, and 0.107
      0.803ng/ml, respectively. The free DHEA-related steroid concentrations were much
      lower than those previously measured by RIA and low-resolution GC-MS. The present
      method made it possible to determine simultaneously serum DHEA-related steroid
      levels with sufficient sensitivity and accuracy.

PMID- 15582538
TI  - Cholesterol modulates maculosin's orientation in model systems of biological
      membranes. Relevance towards putative molecular recognition.
AB  - Fluorescence techniques were used to study (1) the extent of insertion of the
      bioactive cyclic dipeptide cyclo(l-tyrosyl-l-prolyl), maculosin, in model systems
      of membranes of 1, 2-palmitoyl-sn-glycero-3-phosphatidyl choline (DPPC) or 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl choline (POPC), (2) its in-depth
      location in those lipidic membranes, and (3) the influence of cholesterol on the
      dipeptides's location and orientation. Partition into lipidic bilayers is
      extensive, mainly for liquid crystalline phase membranes (K(p)=1.3x10(4)).
      Maculosin locates at the lipid head groups level regardless of the membrane
      system. Nevertheless, its orientation is lipid phase dependent. When maculosin
      was inserted in liquid crystalline phase bilayers, its phenolic ring was
      perpendicular to the membrane surface, whereas it changed orientation when
      inserted in gel phase membranes. Cholesterol was able to reverse the lipid phase
      influence on maculosin's orientation.

PMID- 15582539
TI  - Steroid epimers studied by different mass spectrometric methods.
AB  - The combined use of different mass spectrometric ionization methods and MS/MS
      techniques provide the possibility to differentiate between stereoisomers or
      epimers. In this paper the mass spectral decomposition of 11alpha- and 11beta
      substituted estrans was studied. Distinctive stereochemical effects have been
      observed in their fast atom bombardment product ion spectra. In the electron
      ionisation (EI) mode, the 5alpha- and 5beta-hydroxylated compounds showed
      significant differences in the abundance of water elimination. Mass spectrometry
      has proved to be an effective tool when stereoisomer steroids are compared.

PMID- 15582541
TI  - History and perspective of stem cell research.
AB  - Several types of stem cell have been discovered from germ cells, the embryo,
      fetus and adult. Each of these has promised to revolutionize the future of
      regenerative medicine through the provision of cell-replacement therapies to
      treat a variety of debilitating diseases. Stem cell research is politically
      charged, receives considerable media coverage, raises many ethical and religious
      debates and generates a great deal of public interest. The tremendous versatility
      of embryonic stem cells versus the unprecedented reports describing adult stem
      cell plasticity have ignited debates as to the choice of one cell type over
      another for future application. However, the biology of these mysterious cells
      have yet to be understood and a lot more basic research is needed before new
      therapies using stem-cell-differentiated derivatives can be applied. Stem cell
      research opens-up the new field of 'cell-based therapies' and, as such, several
      safety measures have also to be evaluated.

PMID- 15582542
TI  - The promise of human embryonic stem cells.
AB  - Pluripotency refers to the ability of a cell to give rise to cells that originate
      from all three germ layers. Among the available human pluripotent cells, human
      embryonic stem cells (hESCs) are considered to have the greatest probability for
      practical clinical application because of their simple propagation and stability
      in culture. Since their first derivation, issues concerning hESC maintenance and
      self-renewal have been widely addressed. The first part of this review presents
      the accumulated knowledge concerning the self-renewal of hESCs and discusses
      recent genetic profile data, which seem to shed light on hESC self-renewal and
      pluripotency mechanism. The second part deals with the regenerative potential of
      hESCs. Available lineage-specific differentiations of hESCs are presented, with
      detailed data on the ability of hESCs to differentiate into trophoblast cells, an
      observation that might broaden the definition of their developmental potential.
      Specific focus is given to vascular cell differentiation, including endothelial
      and smooth muscle cells. Transplantation limitations as well as current steps
      taken toward resolution conclude the review.

PMID- 15582543
TI  - Fetal stem cells.
AB  - Fetal stem cells can be isolated from fetal blood and bone marrow as well as from
      other fetal tissues, including liver and kidney. Fetal blood is a rich source of
      haemopoietic stem cells (HSC), which proliferate more rapidly than those in cord
      blood or adult bone marrow. First trimester fetal blood also contains a
      population of non-haemopoietic mesenchymal stem cells (MSC), which support
      haemopoiesis and can differentiate along multiple lineages. In terms of eventual
      downstream application, both fetal HSC and MSC have advantages over their adult
      counterparts, including better intrinsic homing and engraftment, greater
      multipotentiality and lower immunogenicity. Fetal stem cells are less ethically
      contentious than embryonic stem cells and their differentiation potential appears
      greater than adult stem cells. Fetal stem cells represent powerful tools for
      exploring many aspects of cell biology and hold considerable promise as
      therapeutic tools for cell transplantation and ex vivo gene therapy.

PMID- 15582544
TI  - Amniotic fluid and placental stem cells.
AB  - The amniotic fluid and the placenta are unique sources of different populations
      of stem cells--mesenchymal, hematopoietic, trophoblastic--and, possibly, of more
      primitive stem cells. Although much of the amniotic cavity/fluid and the placenta
      share a common embryonic origin, the specific origins of the stem cells found in
      these two compartments remain to be determined. Accordingly, it is not yet known
      whether all or part of these two stem-cell subsets are actually the same. The
      multilineage potential of the different stem cell populations from these two
      sources has begun to be described but still much remains to be learned. Thus, it
      is not surprising that clinical applications related to the use of these cells
      have yet to be reported. Nevertheless, fertile experimental work from many
      different groups has introduced a number of promising novel therapeutic concepts
      utilizing these cells, such as in tissue engineering, cell transplantation, and
      gene therapy.

PMID- 15582545
TI  - Umbilical cord blood stem cells.
AB  - The umbilical cord contains a rich source of haematopoietic stem cells that can
      be used to reconstitute the blood system and can easily be extracted and
      cryopreserved, thus allowing for the establishment of HLA-typed stem cell banks.
      Recently, it has been demonstrated that umbilical cord stem cells have the
      potential to give rise to non-haematopoietic cells, such as bone, neural and
      endothelial cells. It is not clear whether these multipotential cells are
      mesenchymal-like cells or blood cells. Currently, the number of these specialized
      cells capable of undergoing the differentiation process into non-haematopoietic
      cells is low and remains a block to the clinical development of umbilical cord
      stem cells for non-haematopoietic cell therapy. Further research will allow us to
      overcome these hurdles. This expanded potential for umbilical cord stem cells
      might replace embryonic stem cells and other fetal cells for some cell and tissue
      therapies.

PMID- 15582546
TI  - Therapeutic applications of embryonic stem cells.
AB  - Embryonic stem (ES) cells have the potential to proliferate indefinitely in
      culture and can differentiate into any cell type. The emergence of ES cell lines
      from human embryos in the past 5 years has attracted profound public and
      scientific interest, given the far-reaching potential applications of these cells
      in regenerative medicine. In the future, it is possible that human ES (hES) cells
      might serve as an unlimited source of cells for transplantation therapy under
      conditions that result from cell degeneration or malfunction, and that
      genetically manipulated hES cells might serve as vectors to carry and express
      genes in target organs following transplantation in the course of gene therapy.
      This chapter reviews the properties of hES cells and their potential advantages
      and limitations for cell-based therapies. We also describe various approaches
      that might be utilized with hES cells to avoid potential immune rejection after
      allogeneic transplantation and hence circumvent the need for systemic immune
      suppression. Up-to-date research in establishing committed tissue-specific
      progenitors from ES cells and evidence of their function after transplantation in
      various animal disease models is also reviewed. The chapter concludes that hES
      cells show great promise for regenerative medicine although significant
      developments are still required to exploit their potential for cell and gene
      therapy.

PMID- 15582547
TI  - Human embryonic stem cells as a model for early human development.
AB  - Although, the study of human development--from fertilized egg to mature embryo-
      is extremely important, the early differentiation of human tissues remains an
      enigma. Moreover, the relatively high percentage of unexplained pregnancy loss--a
      major concern of human embryologists and gynaecologists--emphasizes the need for
      an appropriate model for studying early human development. The availability of
      human pluripotent stem cells might allow us to study previously inaccessible
      basic processes that occur during human embryogenesis, such as gastrulation and
      organogenesis.

PMID- 15582548
TI  - In utero stem cell transplantation.
AB  - In utero haematopoietic cell transplantation (IUHCT) is a promising approach for
      the treatment of a variety of genetic disorders. The rationale is to take
      advantage of normal events during haematopoietic and immunological ontogeny to
      facilitate allogeneic haematopoietic engraftment. Strategies that will be
      discussed include the direct achievement of therapeutic levels of donor cell
      engraftment by IUHCT, the achievement of adequate levels of engraftment to donor
      specific tolerance by IUHCT, followed by postnatal non-myeloablative regimens to
      enhance levels of donor cell engraftment into the therapeutic range. Although in
      utero haematopoietic cell transplantation has been clinically successful in
      severe combined immunodeficiency disease (SCID), it has been unsuccessful in
      target disorders where there is not a selective advantage for donor cells. This
      chapter presents the recognized barriers to engraftment in the fetus and
      discusses promising experimental strategies to overcome these barriers.

PMID- 15582549
TI  - Fetomaternal cell traffic, pregnancy-associated progenitor cells, and autoimmune
      disease.
AB  - Fetal cells in maternal blood are a potential source of fetal genetic material
      that can be obtained non-invasively. Efforts to isolate these cells from maternal
      peripheral blood are limited by their low circulating numbers (approximately 1
      per ml of maternal blood in euploid pregnancies). Expansion of these cells by
      culture would provide more cells for diagnosis and give an opportunity to study
      fetal metaphase chromosomes. Despite extensive optimization of culture
      conditions, many groups have failed reproducibly to grow fetal cells from pre
      procedural maternal samples. An unexpected benefit of this research has been the
      discovery of a novel population of fetal cells, the pregnancy-associated
      progenitor cell (PAPC), which remains in maternal blood and tissue for decades
      following delivery. These cells might play a role in some autoimmune diseases,
      such as scleroderma. PAPCs appear to have stem cell characteristics, such as the
      ability to proliferate and differentiate. Recently developed animal models will
      help to ascertain whether these cells cause disease, respond to disease, or have
      therapeutic applications.

PMID- 15582550
TI  - Perinatal applications of neural stem cells.
AB  - The brain, unlike many tissues, has a limited capacity for self-repair and so
      there has been great interest in the possibility of transplanting neural cells to
      replace those lost through injury or disease. Encouraging research in humans is
      already underway examining the possibility of neural cell replacement in adult
      neurodegenerative conditions such as Parkinson's disease and Huntington disease.
      In addition, experiments exploring neural stem cell replacement in rodent models
      of acute stroke, demyelination and spinal cord injury have demonstrated
      functional improvements in treated animals. When considering perinatal neural
      stem cell therapy, it should not be overlooked that the immature, developing
      brain might provide a more favourable environment for stem cell integration.
      However, considerable advances need to be made both in understanding the basic
      biology of neural stem cells, including the instructive signals that determine
      their proliferation and differentiation, and in characterising their responses
      when transplanted in a damaged or diseased area of the brain.

PMID- 15582551
TI  - Cord blood banking.
AB  - Cord blood (CB) is a unique product, rich in haemopoietic stem cells (HSC), that
      is currently used in the transplantation setting to restore haemopoiesis. It
      restores haemopoietic stem cell function in patients suffering from malignancies,
      bone marrow (BM) failure disorders and inherited metabolic and immunological
      disorders. Related and unrelated CB donations have been successfully transplanted
      in both the paediatric and adult settings. CB, previously considered a waste
      product, can be collected from both vaginal deliveries and caesarean sections,
      either in utero or ex utero, at no risk to the donor, processed to remove excess
      plasma and red cells, cryopreserved, tested, HLA-typed and stored to provide an
      'off-the-shelf' product. CB has a lower risk of some important viral infections
      and a lower incidence and severity of acute and chronic graft versus host disease
      (GvHD) than BM. CB transplantation is under innovative development and
      international collaborative studies are investigating ways to improve transplant
      outcomes. Other uses for CB remain speculative and it is premature to speculate
      whether non-haemopoietic stem cells are present in cord blood in sufficient
      numbers for use against degenerative conditions, as is currently postulated by
      some commercial organisations. Cord blood banking in EU member countries is now
      regulated by an EU Directive, which provides a statutory basis for regulation
      safety to ensure efficacy. Compliance is required by 2006. It requires that all
      banking establishments are inspected and accredited by a Competent Authority.
      This includes public altruistic banking as well as directed banking activities.

PMID- 15582552
TI  - Following in vitro activation of mitogen-activated protein kinases by mass
      spectrometry and tryptic peptide analysis: purifying fully activated p38 mitogen
      activated protein kinase alpha.
AB  - p38 mitogen-activated protein kinase alpha (MAPKalpha) belongs to the MAPK
      subfamily, which plays a pivotal role in cell signal transduction, where it
      mediates responses to cell stresses and, to a lesser extent, growth factors.
      Although its cellular function has been under intense scrutiny since its initial
      discovery, little progress has been made in understanding its kinetic mechanism.
      A contributory factor has been the lack of a fast and rigorous method for the
      purification of activated p38 MAPKalpha in sufficient quantity and purity for
      biophysical studies. Here we present a method for the preparation of milligram
      quantities of activated p38 MAPKalpha, specifically phosphorylated on Thr180 and
      Tyr182. Purification of the inactive (unphosphorylated) p38 MAPKalpha is
      facilitated by an N-terminal hexahistidine tag. Removal of this tag from His6-p38
      MAPKalpha, prior to its activation, is essential to ensure preparation of high
      yields of homogeneous, dually phosphorylated enzyme. Activation is achieved on
      incubation with a glutathione S-transferase (GST) fusion of the constitutively
      active mutant of the upstream activator, MKK6b (GST-MKK6b S207E T211E), in the
      presence of MgATP2-. Notably, we show that specific formation of activated p38
      MAPKalpha can be quantified by following the formation of the bis-phosphorylated
      tryptic peptide, 173-HTDDEMT*GY*VATR-186, using [gamma-32P]adenosine triphosphate
      (ATP) as the phosphate source and reverse-phase high-performance liquid
      chromatography (HPLC) to separate the phosphopeptides. This approach offers the
      only means to specifically determine both stoichiometry and specificity of p38
      MAPKalpha phosphorylation.

PMID- 15582553
TI  - A live-cell high-throughput screening assay for identification of fatty acid
      uptake inhibitors.
AB  - We developed a live-cell high-throughput assay system using the baker's yeast
      Saccharomyces cerevisiae to screen for chemical compounds that will inhibit fatty
      acid uptake. The target for the inhibitors is a mammalian fatty acid transport
      protein (mmFATP2), which is involved in the fatty acid transport and activation
      pathway. The mmFATP2 was expressed in a S. cerevisiae mutant strain deficient in
      Fat1p-dependent fatty acid uptake and reduced in long-chain fatty acid
      activation, fat1Deltafaa1Delta. To detect fatty acid import, a fluorescent fatty
      acid analog, 4,4-difluoro-5-methyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoic
      acid (C1-BODIPY-C12), was incubated with cells expressing FATP2 in a 96-well
      plate. The mmFATP2-dependent C1-BODIPY-C12 uptake was monitored by measuring
      intracellular C1-BODIPY-C12 fluorescence on a microtiter plate reader, whereas
      extracellular fluorescence was quenched by a cell viability dye, trypan blue.
      Using this high-throughput screening method, we demonstrate that the uptake of
      the fluorescent fatty acid ligand was effectively competed by the natural fatty
      acid oleate. Inhibition of uptake was also demonstrated to occur when cells were
      pretreated with sodium azide or Triacsin C. This yeast live-cell-based assay is
      rapid to execute, inexpensive to implement, and has adequate sensitivity for high
      throughput screening. The assay basis and limitations are discussed.

PMID- 15582554
TI  - A comparison of different strategies for the construction of amperometric enzyme
      biosensors using gold nanoparticle-modified electrodes.
AB  - A comparison of the analytical performances of several enzyme biosensor designs,
      based on the use of different tailored gold nanoparticle-modified electrode
      surfaces, is discussed. Glucose oxidase (GOx) and the redox mediator
      tetrathiafulvalene were coimmobilized in all cases by crosslinking with
      glutaraldehyde. The biosensor designs tested were based on the use of (i)
      colloidal gold (Au(coll)) bound on cysteamine (Cyst) monolayers self-assembled on
      a gold disk electrode (AuE) and (ii) glassy carbon electrodes (GCEs) modified
      with electrodeposited gold nanoparticles (nAu). The results obtained with these
      designs were compared with those provided by a GOx/Cyst-AuE and a GOx/MPA-AuE. In
      the second case (ii), configurations based on direct immobilization of GOx on nAu
      (GOx/nAu-GCE) or on Cyst or MPA self-assembled monolayers (SAMs) previously bound
      on gold nanoparticles (GOx/Cyst-nAu-GCE or GOx/MPA-nAu-GCE, respectively) were
      compared. The analytical characteristics of glucose calibration plots and the
      kinetic parameters of the enzyme reaction were compared for all of the biosensors
      tested. The GOx/Au(coll)-Cyst-AuE design showed a sensitivity for glucose
      determination higher than that achieved with GOx/Cyst-AuE and GOx/Au(coll)
      Cyst/Cyst-AuE and similar to that achieved with GOx/MPA-AuE. Moreover, the useful
      lifetime of one single GOx/Au(coll)-Cyst-AuE was 28 days, remarkably longer than
      that of the other GOx biosensor designs.

PMID- 15582555
TI  - Measurement of the carbohydrate-binding specificity of lectins by a multiplexed
      bead-based flow cytometric assay.
AB  - Carbohydrate binding underlies many cell recognition events. Here, we describe a
      multiplexed glyco-bead array method for determining the carbohydrate-binding
      specificities of plant lectins using a bead-based flow cytometric analysis. N
      glycans including high mannose, hybrid, and complex types and O-glycans from
      glycoproteins were immobilized on multiplexed beads, and the specificities of 13
      kinds of sugar chains were monitored within 2 h in a single reaction. This
      strategy is easy, rapid, reproducible, and suitable for small samples and allows
      the reliable and simultaneous elucidation of sugar-binding properties under
      identical conditions.

PMID- 15582556
TI  - The combination effects of phenolic compounds and fluconazole on the formation of
      ergosterol in Candida albicans determined by high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - A liquid chromatography/tandem mass spectrometry (LC/MS) with atmospheric
      pressure chemical ionization (APCI) for the quantification of ergosterol,
      lanosterol, and squalene was developed to evaluate the combination effects of
      phenolic compounds with fluconazole on ergosterol biosynthesis in Candida
      albicans. The three analytes were separated by a column of C18 and were
      quantified without interference with each other using positive mode tandem mass
      spectrometry (MS/MS). Molecular ions of ergosterol and lanosterol were detected
      as the [M+H-H2O]+ ion species at m/z 380 and 410, whereas squalene appeared as
      the [M+H]+ ion species at m/z 412. On fragmentation of ergosterol, lanosterol,
      and squalene, the product ions at m/z 69, 149, and 109, respectively, were
      present as major fragments. These product ions were used for the quantification
      of them in multiple reaction monitoring acquisition mode. The relationship
      between signal intensity and the analytes' concentration was linear over the
      concentration range of 0.05-10 microg/ml. Following the treatment of C. albicans
      with fluconazole in combination with albicanyl caffeate, resveratrol, and 3,4'
      difluorostilbene, respectively, the content of ergosterol in both the sensitive
      and resistant C. albicans showed depletion, whereas the squalene showed
      accumulation especially in the sensitive isolates determined with the method
      developed.

PMID- 15582557
TI  - Denaturing RNA electrophoresis in TAE agarose gels.
AB  - Current methods of analytical RNA electrophoresis are based on the utilization of
      either complicated laboratory instrumentation or toxic, carcinogenic, or
      expensive chemicals. We suggest here the use of classical Tris-acetate
      ethylenediamine tetraacetic acid (TAE) agarose gels combined with prior
      denaturation of RNA samples in hot formamide for the electrophoretic separation
      of RNA species. We present a brief comparison of the proposed TAE/formamide
      method with the most common 3-(N-morpholino)propanesulfonic acid/formaldehyde
      agarose gel protocol and show that both methods produce comparable results for
      size determination of RNA molecules and subsequent Northern blotting of gels. In
      addition to purified RNA samples, the robustness of the TAE/formamide protocol is
      demonstrated by its suitability for the analysis of RNA quality in crude yeast
      cell lysates containing large amounts of proteins, DNA, and other contaminating
      molecules. We therefore propose the TAE/formamide agarose electrophoresis as a
      rapid, simple, and cheaper alternative to current methods of RNA electrophoresis.
      Additionally, another benefit is the reduced exposure of laboratory personnel to
      hazardous chemicals.

PMID- 15582558
TI  - Simultaneous determination of farnesyl and geranylgeranyl pyrophosphate levels in
      cultured cells.
AB  - A sensitive, nonradioactive analytical method has been developed to
      simultaneously determine the concentrations of farnesyl pyrophosphate (FPP) and
      geranylgeranyl pyrophosphate (GGPP) in cultured cells. Following extraction,
      enzyme assays involving recombinant farnesyl protein transferase or
      geranylgeranyl protein transferase I are performed to conjugate FPP or GGPP to
      dansylated peptides. The reaction products are then separated and quantified by
      high-performance liquid chromatography coupled to a fluorescence detector at the
      excitation wavelength 335 nm and the emission wavelength 528 nm. The retention
      times for farnesyl-peptide and geranylgeranyl-peptide are 8.4 and 16.9 min,
      respectively. The lower limit of detection is 5 pg of FPP or GGPP ( approximately
      0.01 pmol). A linear response has been established over a range of 5-1000 pg (
      approximately 0.01-2 pmol) with good reproducibility. The method has been used to
      determine the levels of FPP (0.125+/-0.010 pmol/10(6)cells) and GGPP (0.145+/
      0.008 pmol/10(6)cells) in NIH3T3 cells. Furthermore, changes in FPP and GGPP
      levels following treatment of cells with isoprenoid biosynthetic pathway
      inhibitors were measured. This method is suitable for the determination of the
      concentrations of FPP and GGPP in any cell type or tissue.

PMID- 15582559
TI  - Determination of coenzyme Q biosynthesis in cultured cells without the necessity
      for lipid extraction.
AB  - Ubiquinone (coenzyme Q; CoQ) is the only lipophilic antioxidant that is
      endogenously synthesized by all organisms. CoQ biosynthesis is determined in
      vitro by supplying a radiolabeled precursor and, after lipid extraction and CoQ
      separation by thin-layer chromatography or high-performance liquid
      chromatography, the radioactivity present in the sample is quantified. In the
      rapid and simple method described here, we avoid the use of organic solvents by
      supplying 4-hydroxy-[U-14C]benzoate as radiolabeled precursor and precipitating
      CoQ with trichloroacetic acid (TCA). After TCA precipitation, all radioactivity
      was present in the precipitate and CoQ was the only radiolabeled molecule
      detected. The radioactive material was then solubilized with NaOH and quantified
      in a scintillation counter.

PMID- 15582560
TI  - Evaluation of two lanthanide complexes for qualitative and quantitative analysis
      of target proteins via partial least squares analysis.
AB  - Two lanthanide complexes, namely 5-aminosalicylic acid
      ethylenediaminetetraacetate europium(III) (5As-EDTA-Eu3+) and 4-aminosalicylic
      acid ethylenediaminetetraacetate terbium(III), were evaluated for the analysis of
      carbonic anhydrase, human serum albumin (HSA), and gamma-globulin. Quantitative
      analysis is based on their luminescence enhancement upon protein binding and
      qualitative analysis on their lifetime capability to recognize the binding
      protein. Analytical figures of merit are presented for the three proteins. The
      limits of detection with 5As-EDTA-Eu3+ are at the parts per billion level.
      Partial least square regression analysis is used to determine HSA and gamma
      globulin in binary mixtures without previous separation at the concentration
      ranges typically found in clinical tests of human blood serum.

PMID- 15582561
TI  - Fluorescence anisotropy assay for proteolysis of specifically labeled fusion
      proteins.
AB  - A cloning method and plasmid vectors that permit fluorescence-anisotropy-based
      measurement of proteolysis are reported. The recombinant protein substrates
      produced by this method contain a tetracysteine motif that can be site
      specifically labeled with bis-arsenical fluorophore [Science 281 (1998) 269]. Six
      protein substrates with an N-terminal fusion of the tetracysteine motif and
      different protease recognition sites were created and tested for reaction with
      commercial proteases commonly used to process recombinant fusion proteins. In
      each case, proteolysis of a single susceptible peptide bond could be monitored in
      real time and with sufficient data quality to allow numerical analysis of
      proteolysis reaction kinetics. Measurement of proteolysis extent using
      fluorescence anisotropy is shown to be comparable to densitometry measurements
      made on denaturing polyacrylamide gels but with the added advantages implicit in
      a time-resolved measurement, quantification by a spectroscopic measurement, and
      facile extensibility to high-throughput formats. The assay was also demonstrated
      as a general tool for monitoring proteolysis of multidomain fusion proteins
      containing an internal protease site such as are being created in structural
      genomics studies worldwide.

PMID- 15582562
TI  - Analysis of the carbohydrate binding specificity of the mushroom Pleurotus
      ostreatus lectin by surface plasmon resonance.
AB  - The sugar binding specificity of the mushroom Pleurotus ostreatus lectin (POL)
      was analyzed by surface plasmon resonance. The lectin was immobilized to a sensor
      chip, and asialo-bovine submaxillary mucin (asialo-BSM), one of the most potent
      inhibitors in the hemagglutination inhibition assay, tightly bound to the lectin.
      The binding specificity of various mono- or oligosaccharides to the lectin was
      evaluated by the coinjection method. The dissociation of asialo-BSM was promoted
      by injection of some haptenic saccharides. For the most part, the order of
      acceleration ability of the sugars to the dissociation in the coinjection
      experiment agreed with that of the inhibitory potency of each sugar evaluated by
      the hemagglutination inhibition assay. In conclusion, POL recognized a galactosyl
      residue, and the specificity was increased by substitution at the C-2 position of
      the galactosyl residue with a fucosyl or acetylamino group. This method using the
      coinjection method proved useful in analysis of carbohydrate-lectin binding
      specificity.

PMID- 15582563
TI  - Applications of capillary isoelectric focusing with liquid-core waveguide laser
      induced fluorescence whole-column imaging detection.
AB  - Capillary isoelectric focusing (CIEF) with liquid-core waveguide (LCW) laser
      induced fluorescence (LIF) whole-column imaging detection (WCID) is a recently
      developed high-resolution, high-sensitivity, and high-speed analytical tool for
      protein analysis. Several potential applications of this system were demonstrated
      in this study. First, this system was employed to separate naturally fluorescent
      phycobiliproteins. Second, denaturing CIEF was suggested to study the
      conformational and chemical microheterogeneity and to characterize proteins with
      identical pI values. Third, a modified noncovalent fluorescent labeling procedure
      was presented, which allows the simple and effective labeling of proteins,
      antibodies, and viruses with reduced multiple labeling and preserved activity.
      Finally, extracellular proteins were suggested as signaling biomarkers for
      evaluation of cell viability. The separation of cyanobacteria and their
      extracellular phycoerythrins was demonstrated. The effectiveness of CIEF-LCW-LIF
      WCID for the analysis of proteins, antibodies, viruses, and cells has been
      illustrated.

PMID- 15582564
TI  - Homogeneous enzyme immunoassay modified for application to luminescence-based
      biosensors.
AB  - Application of immunoassay to biosensors for use in the point-of-care setting
      ideally requires immunoassay without separation steps and with small volumes of
      both sample and reagents. The suitability of cloned enzyme donor immunoassay
      (CEDIA), one of a few homogeneous immunoassays available, was investigated for
      application to biosensors. This method is based on the bacterial enzyme beta
      galactosidase, which has been genetically engineered by others into two inactive
      fragments, enzyme donor (ED) and enzyme acceptor (EA). Association of the ED and
      EA fragments in the assay results in formation of active enzyme, which acts on
      substrate to generate a detectable signal. Sensitivity of commercially available
      CEDIA kits were compared, with respect to the sample and reagent volumes, using
      three different signal generation processes. The CEDIA kit for valproic acid and
      three substrates, a colorimetric (chlorophenol red-beta-D-galactopyranoside), a
      chemiluminescent (Lumi-Gal 530), and a bioluminescent (Beta-Glo Assay System),
      were employed in the study. Our results indicate that the high sensitivity of the
      bioluminogenic substrate, D-luciferin-O-beta-galactopyranoside, with short assay
      time and small volumes of sample and reagents required for the assay, simple
      handling, and relatively low expense, make this substrate, together with CEDIA,
      suitable for application to biosensors intended for drug and metabolite
      monitoring in the point-of-care setting.

PMID- 15582565
TI  - Stereoselective histidine sensor based on molecularly imprinted sol-gel films.
AB  - A piezoelectric sensor coated with a thin molecularly imprinted sol-gel film has
      been developed for the determination of L-histidine in the liquid phase. Without
      preprotection, L-histidine was imprinted directly into silica sol-gel films that
      consisted of a hybrid mixture of functionalized organosilicon precursors
      (phenyltrimethoxysilane and methyltrimethoxysolane). The viscoelasticity of the
      film in the air and in buffer solution has been studied by the piezoelectric
      quartz crystal impedance technique. The binding of L-histidine to the imprinted
      film in the liquid phase was investigated by the piezoelectric microgravimetry
      and electrochemical impedance technique. Scatchard analysis showed that the
      maximum binding site (Qmax) of the L-histidine imprinted sol-gel film is about
      23.7 micromol/g. A linear range from 5.0x10(-8) to 1.0x10(-4) M for a detection
      of L-histidine has been observed with a detection limit of 2.5x10(-8) M for
      S/N=3. The proposed imprinted sol-gel sensor exhibits good stability, high
      specificity, and excellent stereoselectivity.

PMID- 15582566
TI  - A colorimetric determination for glycosidic and bile salt-based detergents:
      applications in membrane protein research.
AB  - Detergents are crucial to the isolation of integral membrane proteins. During
      membrane protein purification, it is useful to accurately quantify detergent,
      especially if concentration steps have been used. Previously, this has been
      difficult and time-consuming. We present a simple, rapid, and sensitive procedure
      for the quantification of glycosidic and bile salt-based detergents such as
      dodecylmaltoside, octylglucoside, and CHAPS. The method directly quantifies sugar
      or cholate moieties via colorimetric reactions with phenol and sulfuric acid. A
      number of detergents have been screened, and the assay has been validated in the
      presence of commonly used reagents. In addition to determining the overall
      detergent concentration in solution, the procedure allows accurate quantification
      of specific binding of glycosidic or bile salt-based detergents to purified
      membrane proteins. Both the colorimetric method and the radiometric 14C method
      were used to determine detergent binding to two integral membrane proteins: the
      cytochrome cbb3 oxidase from Pseudomonas stutzeri and the turkey beta-adrenergic
      receptor. Both methods gave similar results. After separating monomeric
      glycosidic detergent from micellar solutions by ultrafiltration, we used the
      colorimetric method to determine the concentration of monomeric detergent
      present. We observed that values obtained are in close agreement with previously
      determined critical micelle concentrations.

PMID- 15582567
TI  - A fluorescence-based assay for 2-oxoglutarate-dependent oxygenases.
AB  - A widely used generic assay for 2-oxoglutarate-dependent oxygenases relies upon
      monitoring the release of 14CO2 from labeled [1-14C]-2-oxoglutarate. We report an
      alternative assay in which depletion of 2-oxoglutarate is monitored by its
      postincubation derivatization with o-phenylenediamine to form a product amenable
      to fluorescence analysis. The utility of the procedure is demonstrated by assays
      with hypoxia-inducible factor hydroxylases where it was shown to give results
      similar to those reported with the radioactive assay, but it is more efficient
      and readily adapted to a multiwell format. The process should be amenable to the
      assay of other 2-oxoglutarate-consuming enzymes and to the discovery of
      inhibitors.

PMID- 15582568
TI  - 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide interference with Lowry method.
AB  - 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) was tested for interference
      with the Lowry method of protein determination. The EDC interference was nearly
      additive at both 660 and 750 nm. Blue-colored complex developed in the case of
      EDC and showed maximum absorbance at 750 nm, similar to the bovine serum albumin
      (BSA) estimation. In time response analysis, blue-colored complex was developed
      after 30 min of incubation in both cases (EDC and BSA); therefore, it followed
      the same kinetic pattern of color development as that of BSA. Interference is
      believed to be caused by the reduction of the folin-ciocalteu reagent by EDC,
      resulting in increased blue-colored complex and apparently causing increased
      protein content of the sample.

PMID- 15582569
TI  - Green fluorescent protein as a reporter in translational assays.

PMID- 15582570
TI  - Production of research-grade antibody by in vivo electroporation of DNA-encoding
      target protein.

PMID- 15582571
TI  - Chemiluminescence detection of arginine-containing peptides separated with
      monolithic high-performance liquid chromatography.

PMID- 15582572
TI  - GnRH pre-mRNA splicing: solving the mystery of a nature's knockout, hpg mouse.
AB  - The hypogonadal (hpg) mouse represents a unique animal model for hypogonadism. In
      this mutant the truncation of the gene encoding gonadotropin-releasing hormone
      (GnRH) leads to drastically lowered gonadotropin levels and prepubertal gonads.
      The deletional mutation encompasses only the distal half of the gene leaving the
      region encoding GnRH decapeptide intact. The partially deleted gene is
      transcriptionally active, but translationally inactive. Even though several
      aspects have been considered to account for the phenomenon, there is no
      satisfactory explanation so far. Recent reports showed that excision of the GnRH
      first intron is delicately regulated in a cell type- and developmental stage
      specific manner mediated by putative-specific splicing factors acting on cis
      acting elements located in exon 3 and 4, and is significantly decreased in hpg
      mouse whose exonic splicing enhancers are absent. Furthermore, the suppressing
      effect of intron A retention on the translational activity of downstream open
      reading frame was reported, giving an insight into the understanding the mystery
      of hpg mice.

PMID- 15582573
TI  - BRE enhances in vivo growth of tumor cells.
AB  - Human BRE, a death receptor-associating intracellular protein, attenuates
      apoptotic response of human and mouse tumor cell lines to death receptor stimuli
      in vitro. In this report, we addressed whether the in vitro antiapoptotic effect
      of BRE could impact on tumor growth in vivo. We have shown that the mouse Lewis
      lung carcinoma D122 stable transfectants of human BRE expression vector developed
      into local tumor significantly faster than the stable transfectants of empty
      vector and parental D122, in both the syngeneic C57BL/6 host and nude mice. In
      vitro growth of the BRE stable transfectants was, however, not accelerated. No
      significant difference in metastasis between the transfectants and the parental
      D122 was detected. Thus, overexpression of BRE promotes local tumor growth but
      not metastasis. We conclude that the enhanced tumor growth is more likely due to
      the antiapoptotic activity of BRE than any direct effect of the protein on cell
      proliferation.

PMID- 15582574
TI  - Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric
      cancer cells.
AB  - Our previous study has shown that matrix metalloproteinase 11 (MMP11) is highly
      expressed in tumor cell lines and primary tumor of gastric cancer (GC). In order
      to reveal the correlation between expression of MMP11 and biological features of
      GC cell, we have constructed the recombinant plasmids producing hairpin small
      interfering RNA (siRNA) to target MMP11 mRNA using a vector-based RNA
      interference technology. Stable transfection of recombinants into GC cell line
      BGC823 specifically depleted the mRNA and protein of MMP11 as demonstrated by RT
      PCR and Western blotting analysis. The siRNA-treated cells exhibited
      significantly decreased growth ability compared with mock transfectants and
      parental BGC823 cells. Furthermore, colony formation of MMP11 deficient cells was
      dramatically inhibited in soft agar and tumorigenicity was reduced in nude mice,
      respectively. These results provide new insights into the function of MMP11 and
      suggest that MMP11 may play an important role in the control of cell
      proliferation and tumor development in GC.

PMID- 15582575
TI  - Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer
      cells by signaling via the mitochondrial pathway.
AB  - Alpha-tocopheryl succinate (alpha-TOS) is a redox-silent vitamin E (VE) analog
      with high pro-apoptotic and anti-neoplastic activity. Here we investigated
      whether alpha-TOS and several novel VE analogs kill breast cancer cells over
      expressing the anti-apoptotic receptor protein HER2/erbB2. The agents induced
      apoptosis at comparable levels in both erbB2-low and -high cells. Generation of
      reactive oxygen species (ROS) preceded mitochondrial destabilization and
      execution of apoptosis, as evidenced by the anti-apoptotic effects of exogenous
      superoxide dismutase and mitochondrially targeted coenzyme Q. Dissipation of
      DeltaPsi(m) was followed by cytochrome c and Smac/Diablo re-localization and
      caspase-dependent cleavage of death substrate. A resistance to apoptosis for the
      corresponding rho(0) counterparts confirmed a critical dependency for
      mitochondria during the induction of apoptosis in breast cancer cells mediated by
      VE analogs and linked apoptosis to generation of radicals as judged by the
      delayed accumulation of ROS in the cybrid cell types. We conclude that alpha-TOS
      causes efficient apoptosis in breast cancer cells independent of their erbB2
      status. Since erbB2 is frequently over-expressed in breast cancers and renders
      the neoplastic disease resistant to established treatment, our findings are of
      clinical interest.

PMID- 15582576
TI  - Mutational study of the bacterial hemoglobin distal heme pocket.
AB  - Ligand binding experiments on three mutants in the distal heme pocket of
      Vitreoscilla hemoglobin (GlnE7His, ProE8Ala, and GlnE7His,ProE8Ala) were used to
      probe the role of GlnE7 and ProE8 in the pocket's unusual structure. The oxygen
      dissociation constants for the wild type, E8Ala mutant, and E7His mutant proteins
      were 4.5, 4.7, and 1.7microM, respectively; the K(d) for the double mutant was
      not determinable by our technique. Visible-Soret spectra of the carbonyl and
      cyanyl forms and FT-IR of the carbonyl form of the E8 mutant were similar to
      those of the wild type; the opposite was true for the GlnE7His and
      GlnE7His,ProE8Ala mutants, which also differed from wild type in the visible
      Soret spectra of their oxidized forms. Models of the effects of the mutations on
      distal pocket structure were consistent with the experimental findings,
      particularly the larger effects of the GlnE7His change.

PMID- 15582577
TI  - Nanoscale orientation and lateral organization of chimeric metal-binding green
      fluorescent protein on lipid membrane determined by epifluorescence and atomic
      force microscopy.
AB  - Epifluorescence microscopy as well as atomic force microscopy was successfully
      applied to explore the orientation and lateral organization of a group of
      chimeric green fluorescent proteins (GFPs) on lipid membrane. Incorporation of
      the chimeric GFP carrying Cd-binding region (His6CdBP4GFP) to the fluid phase of
      DPPC monolayer resulted in a strong fluorescence intensity at the air-water
      interface. Meanwhile, non-specific adsorption of the GFP having hexahistidine
      (His6GFP) led to the perturbation of the protein structure in which very low
      fluorescence was observed. Specific binding of both of the chimeric GFPs to
      immobilized zinc ions underneath the metal-chelating lipid membrane was revealed.
      This specific binding could be reversibly controlled by addition of metal ions or
      metal chelator. Binding of the chimeric GFPs to the metal-chelating lipid
      membrane was proven to be the end-on orientation while the side-on adsorption was
      contrarily noted in the absence of metal ions. Increase of lateral mobility owing
      to the fluidization effect on the chelating lipid membrane subsequently
      facilitated crystal formation. All these findings have opened up a potential
      approach for a specific orientation of immobilization of protein at the membrane
      interface. This could have accounted for a better opportunity of sensor
      development.

PMID- 15582578
TI  - Long-term in vivo and in vitro AAV-2-mediated RNA interference in rat retinal
      ganglion cells and cultured primary neurons.
AB  - Viral vector-based expression of small interfering RNAs is a promising tool for
      gene regulation, both in cultured cells and in animal models. In this study, we
      analysed the ability of adeno-associated virus-2 to function as an RNAi vector in
      cultured primary hippocampal neurons in vitro and in retinal ganglion cells in
      vivo. We demonstrate a long-lasting, highly efficient, and specific down
      regulation of gene expression in vivo and in vitro by the use of bicistronic
      vectors. This is the first evidence of a cell type-specific long-term (more than
      three-month-long) RNAi in the eye. Furthermore, our results constitute the
      prerequisite for the use of this technique in models of neurodegeneration and
      neuroregeneration in vivo and in vitro.

PMID- 15582579
TI  - Pivotal participation of nitrogen dioxide in L-arginine induced acute necrotizing
      pancreatitis: protective role of superoxide scavenger 4-OH-TEMPO.
AB  - For the first time, a direct sensitive method of *NO(2) detection and measurement
      in biological material has been established. It is based on the interaction of
      this radical with the coordination compound of Cr(III) with aminodeoxysugar as
      biosensor. Our new method makes it possible to precisely assess *NO(2) level in
      experimental acute necrotizing pancreatitis induced by L-arginine, where
      oxidative and nitrosative stresses are supposed to play a key role in the
      pathomechanism of the disease. As much as 20 nmol of *NO(2)/mg protein was
      detected which correlated with severe deterioration of pancreatic acinar cell
      ultrastructure. Protective effect of superoxide radical scavenger 4-OH-TEMPO
      expressed as *NO(2) level decrease confirmed by preserved acinar cell
      ultrastructure and decreased pancreatic amylase release to blood serum is
      demonstrated. This study reveals a possible pathomechanism of L-arginine induced
      acute pancreatitis.

PMID- 15582580
TI  - Proteomic analysis of nicotine-associated protein expression in the striatum of
      repeated nicotine-treated rats.
AB  - Through the proteomic analysis using 2-dimensional electrophoresis, the nicotine
      addiction-associated proteins were extensively screened in the striatum of rat
      brains. The nicotine addiction was developed by repeated nicotine injection
      (0.4mg/kg s.c.), twice daily for 7 days, followed by one challenge injection
      after a 3 day withdrawal period, and then confirmed by observing a 2.3-fold
      increase in locomoter activity. The 3 up- and 4 down-regulated proteins were
      selected and identified to be zinc-finger binding protein-89 (ZBP-89), 2'3'
      cyclic nucleotide 3'-phosphodiesterase 1, deoxyribonuclease 1-like 3 (DNase1l3),
      tandem pore domain halothane inhibited K(+) channel (THIK-2), brain-specific
      hyaluronan-binding protein (BRAL-1), death effector domain-containing DNA binding
      protein (DEDD), and brain-derived neurotrophic factor (BDNF) by mass
      spectrophotometric fingerprinting. Among them, the expression patterns of ZEB-89,
      DNase1l3, THIK-2, DEDD, and BDNF mRNAs were found to be coincident with those of
      cognate proteins, by using RT-PCR analysis. These proteins could be suggested as
      drug targets to develop a new therapy for nicotine-associated diseases, as well
      as the clues to understand the mechanism of nicotine.

PMID- 15582581
TI  - ATP-stimulated interleukin-6 synthesis through P2Y receptors on human
      osteoblasts.
AB  - We investigated the effect of extracellular adenosine triphosphate (ATP) on the
      production of interleukin (IL)-6, whose molecules are capable of stimulating the
      development of osteoclasts from their hematopoietic precursors as well as are
      involved in signal transduction systems in human osteoblastic SaM-1 cells. These
      human osteoblasts constitutively expressed P2X4, P2X5, P2X6, P2Y2, P2Y5, and P2Y6
      purinergic receptors. ATP increased gene- and protein-expression of IL-6 in SaM-1
      cells. The expression of the IL-6 mRNA was maximal at 1h, and the increase in IL
      6 synthesis in response to ATP (10-100 microM) occurred in a concentration
      dependent manner. Over the same concentration range of the nucleotide that was
      effective for IL-6 synthesis, ATP caused an increase in the intracellular Ca(2+)
      concentration ([Ca(2+)](i)), which increase was inhibited by pretreatment with
      suramin, a P2Y receptor antagonist, or 2-aminoethoxydiphenyl borate (2-APB), an
      inositol 1,4,5-trisphosphate receptor blocker, but not by the extracellular
      Ca(2+)-chelating agent EGTA. The pretreatment of SaM-1 cells with suramin or 2
      APB also inhibited the increase in IL-6 synthesis in response to ATP. These
      findings suggest that extracellular ATP-induced IL-6 synthesis occurs through P2Y
      receptors and mobilization of Ca(2+) from internal stores in human osteoblastic
      cells.

PMID- 15582582
TI  - Crystal structure of human PNP complexed with hypoxanthine and sulfate ion.
AB  - Purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme, which plays a key
      role in the purine salvage pathway, and PNP deficiency in humans leads to an
      impairment of T-cell function, usually with no apparent effects on B-cell
      function. Human PNP has been submitted to intensive structure-based design of
      inhibitors, most of them using low-resolution structures of human PNP. Here we
      report the crystal structure of human PNP in complex with hypoxanthine, refined
      to 2.6A resolution. The intermolecular interaction between ligand and PNP is
      discussed.

PMID- 15582583
TI  - Breakage of PrP aggregates is essential for efficient autocatalytic propagation
      of misfolded prion protein.
AB  - The conversion of cellular prion protein (PrP(C)) to the disease-associated
      misfolded isoform (PrP(Sc)) is an essential process for prion replication. This
      structural conversion can be modelled in protein misfolding cyclic amplification
      (PMCA) reactions in which PrP(Sc) is inoculated into healthy hamster brain
      homogenate, followed by cycles of incubation and sonication. In serial
      transmission PMCA experiments it has recently been shown that the protease
      resistant PrP obtained in vitro (PrPres) is generated by an autocatalytic
      mechanism. Here, serial transmission PMCA experiments were compared with serial
      transmission reactions lacking the sonication steps. We achieved approximately
      200,000-fold PrPres amplification by PMCA. In contrast, although initial
      amplification was comparable to PMCA reactions, PrPres levels quickly dropped
      below detection limit when samples were not subjected to ultrasound. These
      results indicate that aggregate breakage is essential for efficient autocatalytic
      amplification of misfolded prion protein and suggest an important role of
      aggregate breakage in prion propagation.

PMID- 15582584
TI  - Age-dependent suppression of SERCA2a mRNA in pediatric atrial myocardium.
AB  - Differential expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and
      phospholamban (PLB) has been shown in heart failure and atrial arrhythmias. We
      investigated the influence of volume overload and age on their expression in
      pediatric atrial myocardium. Right atrial specimens from 18 children with volume
      overloaded right atrium (VO) and 12 patients without overload were studied. Each
      group was further divided into patients less than and older than 12 months of
      age. Only in the younger patients SERCA2a was significantly reduced in the VO
      group. In younger patients PLB mRNA level tended to be lower in VO. The PLB:SERCA
      protein ratio was significantly reduced in the VO group. Age itself did not
      influence the SERCA2a and PLB expression, if the hemodynamic overload was not
      taken into account. This study is the first to show a combined influence of
      volume overload and age on atrial SERCA2a expression.

PMID- 15582585
TI  - Melanocortin receptors form constitutive homo- and heterodimers.
AB  - A significant number of G protein-coupled receptors are shown to form homo- or
      heterodimers/oligomers, and oligomerization of GPCRs may be a quite general
      phenomenon. We have here explored the possibility that the two closely related
      human melanocortin receptor 1 (MC(1)R) and melanocortin receptor 3 (MC(3)R) form
      dimers. Using bioluminescence resonance energy transfer (BRET(2)) we demonstrate
      that MC(1) and MC(3)Rs form homo- and heterodimers, when expressed in Cos-7
      cells. Treatment with agonist, partial agonist or antagonists did not modify the
      BRET(2) signal for any of the receptor pairs studied, suggesting that the
      dimerization is not regulated by ligand binding. Rather our results indicate that
      melanocortin receptors exist as constitutively pre-formed dimers.

PMID- 15582586
TI  - Functional preservation of duplicated pair for RSVS III gene in the REST locus of
      rat 3q42.
AB  - Among the major proteins in the rat seminal vesicle secretion, transglutaminase
      catalyzed the cross-links among RSVS I-III. Six peptide sequences determined from
      the trypsin digests of RSVS III were confirmed in the protein sequence derived
      from two paralogs, RSVS III(alpha) and RSVS III(beta) gene, in rat 3q42. Their
      transcription units are organized with the first exon encoding a signal peptide,
      and the second a secreted protein, whereas the third encompasses a 3'-non
      translated nucleotide that shares common features of rapidly evolving substrates
      of transglutaminase (REST) gene family. These two genes have 99% identity in
      their coding region and both express in adult rats with the same transglutaminase
      cross-linking site, manifesting functional preservation. All of REST genes
      reported thus far for human and Muridae were mapped in a chromosomal locus
      between KCNS1 and SLPI suggesting the locus as an active evolving region. The
      molecular evolution of this gene family is discussed.

PMID- 15582587
TI  - KC chemokine expression by TGF-beta in C3H10T1/2 cells induced towards
      osteoblasts.
AB  - The effects of TGF-beta on expression of the platelet-derived growth factor
      induced KC protein were explored in mouse mesenchymal C3H10T1/2 and pre
      osteoblastic MC3T3-E1 cells to identify a potential role for TGF-beta in
      expression of angiogenic cytokines during osteogenic differentiation. KC is a
      member of the CXC chemokine family with homology to human IL-8, a potent
      neutrophilic chemotactic cytokine. TGF-beta treatment results in increased KC
      mRNA and protein secretion in C3H10T1/2 induced towards the osteoblastic lineage
      with all-trans-retinoic acid. This is due to up-regulated transcription rather
      than enhanced mRNA stability. No induction of KC expression was seen in untreated
      C3H10T1/2 or MC3T3-E1 upon TGF-beta stimulation. Use of the translational
      inhibitor cycloheximide results in mRNA "superinduction" suggesting other factors
      are involved that normally function to down-regulate KC expression. TGF-beta
      stimulated conditioned media were a potent chemostimulant for human microvascular
      endothelial cells (HMEC-1). This activity could be inhibited by pre-incubation
      with anti-KC neutralizing antibodies.

PMID- 15582588
TI  - Coordinate regulation of glutathione metabolism in astrocytes by Nrf2.
AB  - The tripeptide glutathione (GSH) represents the major brain thiol and is
      essential for prevention of oxidative stress. Using monochlorobimane to label
      intracellular GSH in a glutathione S-transferase catalyzed reaction we have
      examined the kinetics of GSH metabolism including its rate of conjugation, total
      GSH content, synthesis, and efflux in astrocyte cultures under basal conditions
      and after induction of antioxidant response element (ARE)-mediated gene
      expression by the transcription factor Nrf2. In the presence of a cerebral spinal
      fluid-like salt solution astrocytes could not synthesize detectable levels of
      GSH. Addition of GSH precursors, cystine, glutamate, and glycine, rapidly
      restored GSH synthesis. Astrocytes were able to use either glutamate or glutamine
      as precursors equally for GSH synthesis. Using the small molecule chemical
      inducer tert-butylhydroqunione (tBHQ) we report that induction of ARE-mediated
      gene expression is associated with a coordinated increase in GSH content and
      synthesis rate with little effect on the rate of GSH conjugation or efflux.
      Consistent with the effect of the inducer, adenovirus-mediated overexpression of
      the transcription factor Nrf2 that mediates tBHQ's effects also increased GSH
      content, confirming that GSH metabolism can be regulated by the Nrf2 pathway.

PMID- 15582589
TI  - Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids
      act as potent and reversible inhibitors.
AB  - Monoamine oxidase (MAO) is a mitochondrial outer-membrane flavoenzyme involved in
      brain and peripheral oxidative catabolism of neurotransmitters and xenobiotic
      amines, including neurotoxic amines, and a well-known target for antidepressant
      and neuroprotective drugs. Recently, positron emission tomography imaging has
      shown that smokers have a much lower activity of peripheral and brain MAO-A (30%)
      and -B (40%) isozymes compared to non-smokers. This MAO inhibition results from a
      pharmacological effect of smoke, but little is known about its mechanism. Working
      with mainstream smoke collected from commercial cigarettes we confirmed that
      cigarette smoke is a potent inhibitor of human MAO-A and -B isozymes. MAO
      inhibition was partly reversible, competitive for MAO-A, and a mixed-type
      inhibition for MAO-B. Two beta-carboline alkaloids, norharman (beta-carboline)
      and harman (1-methyl-beta-carboline), were identified by GC-MS, quantified, and
      isolated from the mainstream smoke by solid phase extraction and HPLC. Kinetics
      analysis revealed that beta-carbolines from cigarette smoke were competitive,
      reversible, and potent inhibitors of MAO enzymes. Norharman was an inhibitor of
      MAO-A (K(i)=1.2+/-0.18 microM) and MAO-B (K(i)=1.12+/-0.19 microM), and harman of
      MAO-A (K(i)=55.54+/-5.3nM). Beta-carboline alkaloids are psychopharmacologically
      active compounds that may occur endogenously in human tissues, including the
      brain. These results suggest that beta-carboline alkaloids from cigarette smoke
      acting as potent reversible inhibitors of MAO enzymes may contribute to the MAO
      reduced activity produced by tobacco smoke in smokers. The presence of MAO
      inhibitors in smoke like beta-carbolines and others may help us to understand
      some of the purported neuropharmacological effects associated with smoking.

PMID- 15582590
TI  - Expression of angiogenesis factors in human umbilical vein endothelial cells and
      their regulation by PEDF.
AB  - The VEGFs and FGF-2 stimulate angiogenesis. Pigment epithelium-derived factor
      (PEDF) and thrombospondin-1 (TSP-1) strongly inhibit angiogenesis. Human
      umbilical vein endothelial cells (HUVECs) expressed VEGF-A, -B, -C, the VEGF
      receptors R1, R2, and R3, PEDF, FGF-2, and TSP-1, but VEGF-D transcripts were
      barely detectable. Hypoxia reduced the transcript levels of VEGF-C and its
      cognate receptor, VEGF-R3. PEDF blocked the effect of CoCl(2) on these two
      factors. The expression of VEGF-A and -B as well as VEGF-R1 and VEGF-R2 remained
      unchanged after exposure to hypoxia, PEDF, or both. There was a marked reduction
      in TSP-1 transcripts in CoCl(2) treated cultures and PEDF blocked this reduction.
      PEDF induced a small increase in FGF-2 transcripts in HUVECs, but there was no
      change in FGF-2 expression in HUVECs exposed to hypoxia or hypoxia plus PEDF.
      PEDF may control neovascularization, in part, by restoring the negative effects
      of hypoxia on the expression of a potent angiogenesis inhibitor, TSP-1. PEDF may
      also modulate vascular leakage by maintaining the transcriptional levels of the
      vascular homeostasis factors, VEGF-C and VEGF-R3 in hypoxic conditions.

PMID- 15582591
TI  - Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene
      expression.
AB  - In a model of human neuroblastoma (NB) cell lines persistently infected with
      human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection
      is associated with an increased malignant phenotype, enhanced drug resistance,
      and invasive properties. To gain insights into the mechanisms of increased
      malignancy we analyzed the global changes in cellular gene expression induced by
      persistent HCMV infection of human neuroblastoma cells by use of high-density
      oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene
      expression of different NB cell lines with persistently infected cell sub-lines
      revealed 11 host cell genes regulated in a similar manner throughout all infected
      samples. Nine of these 11 genes may contribute to the previously observed changes
      in malignant phenotype of persistently HCMV infected NB cells by influencing
      invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work
      provides the basis for further functional studies.

PMID- 15582592
TI  - Constitutively active PDX1 induced efficient insulin production in adult murine
      liver.
AB  - To generate insulin-producing cells in the liver, recombinant adenovirus
      containing a constitutively active mutant of PDX1 (PDX1-VP16), designed to
      activate target genes without the need for protein partners, was prepared and
      administered intravenously to streptozotocin (STZ)-treated diabetic mice. The
      effects were compared with those of administering wild-type PDX1 (wt-PDX1)
      adenovirus. Administration of these adenoviruses at 2x10(8)pfu induced similar
      levels of PDX1 protein expression in the liver. While wt-PDX1 expression exerted
      small effects on blood glucose levels, treatment with PDX1-VP16 adenovirus
      efficiently induced insulin production in hepatocytes, resulting in reversal of
      STZ-induced hyperglycemia. The effects were sustained through day 40 when
      exogenous PDX1-VP16 protein expression was undetectable in the liver. Endogenous
      PDX1 protein came to be expressed in the liver, which is likely to be the
      mechanism underlying the sustained effects. On the other hand, albumin and
      transferrin expressions were observed in insulin-producing cells in the liver,
      suggesting preservation of hepatocytic functions. Thus, transient expression of
      an active mutant of PDX1 in the liver induced sustained PDX1 and insulin
      expressions without loss of hepatocytic function.

PMID- 15582593
TI  - Induction of expression of inducible nitric oxide synthase by Taxol in murine
      macrophage cells.
AB  - Paclitaxel (Taxol), a microtubule stabilizer with antitumor activity, mimics
      certain effects of lipopolysaccharide (LPS) in murine macrophages. We examined
      the mechanism by which Taxol regulates the expression of inducible nitric oxide
      synthase (iNOS) in a murine macrophage cell line. Taxol alone induced iNOS mRNA
      and promoter activity, but no iNOS protein or NO production. The stability of the
      iNOS mRNA formed in response to Taxol was lower than that formed in response to
      IFN-gamma or LPS, and this may have been responsible for the lack of induction of
      iNOS protein and NO. However, IFN-gamma synergized with Taxol by increasing iNOS
      mRNA stability, and upregulating levels of iNOS mRNA and protein, promoter
      activity, and NO production. Transfection experiments with 5'-serial deletions
      and site-directed mutants of the iNOS promoter revealed that the pair of upstream
      and downstream NF-kappaB sites was crucial for promoter activity in response to
      Taxol, as in the case of LPS. Electrophoretic mobility shift assays showed that
      both Taxol and LPS rapidly activated identical NF-kappaB complexes that could
      bind to the iNOS promoter. These results suggest that Taxol shares a signaling
      pathway for transcriptional activation of iNOS with LPS, but that the stability
      of the iNOS mRNA induced by Taxol is different from that induced by LPS.

PMID- 15582594
TI  - Biochemical and growth regulatory activities of the HIN-200 family member and
      putative tumor suppressor protein, AIM2.
AB  - The human HIN-200 family member AIM2 was originally identified in a screen for
      suppressors of melanoma tumorigenicity following introduction of chromosome 6
      into the UACC903 human melanoma cell line. Although the AIM2 protein contained
      many of the conserved structural motifs common to other HIN-200 proteins, the
      biochemical characteristics of AIM2 and the ability of overexpressed AIM2 to
      phenocopy the effect of introduction of chromosome 6 in the UACC903 cells had not
      been assessed. Herein we demonstrated that AIM2 was localised within the nucleus
      of transfected or interferon-treated human cells. In addition, AIM2 could
      homodimerise via the amino-terminal (PAAD/DAPIN) region and heterodimerise with
      the related IFI 16 protein. However, overexpressed AIM2 did not significantly
      affect the growth or survival of UACC903 cells or another human melanoma cell
      line. These data indicate that AIM2 has many of the biochemical and structural
      characteristics of HIN-200 proteins, however, its expression is not sufficient to
      induce a tumor-suppressor-like phenotype.

PMID- 15582595
TI  - Isolation and characterization of neural stem cells from human fetal striatum.
AB  - This paper described that neural stem cells (hsNSCs) were isolated and expanded
      rapidly from human fetal striatum in adherent culture. The population was serum-
      and growth factor-dependent and expressed neural stem cell markers. They were
      capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes.
      When plated in the dopaminergic neuron inducing medium, human striatum neural
      stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs
      were morphologically homogeneous and possessed high proliferation ability. The
      population doubled every 44.28h and until now it has divided for more than 82
      generations in vitro. Normal human diploid karyotype was unchanged throughout the
      in vitro culture period. Together, this study has exploited a method for
      continuous and rapid expansion of human neural stem cells as pure population,
      which maintained the capacity to generate almost fifty percent neurons. The
      availability of such cells may hold great interest for basic and applied
      neuroscience.

PMID- 15582596
TI  - Cloning and expression of a new member of prolactin-related protein in bovine
      placenta: bovine prolactin-related protein-VII.
AB  - This study reports the identification and sequence of a full-length cDNA for a
      new member of bovine prolactin-related protein (bPRP-VII) and its quantitative
      and localized expression in the placenta. A full-length bPRP-VII cDNA was cloned
      with a 929-nucleotide open-reading-frame corresponding to a protein of 238 amino
      acids. The predicted amino acid sequence shares 63% homology with bPRP-I and 70%
      with bPRP-VI. bPRP-VII has eight cysteine residues with four disulfide bonds,
      which is more abundant than that of other bPRPs. RT-PCR detected bPRP-VII only in
      the placenta. In the placenta, mRNA was expressed in the cotyledon and
      intercotyledonary tissues throughout gestation. Quantitative real-time RT-PCR
      analysis exhibited a high expression of bPRP-VII mRNA in the fetal membrane at
      Day 27 of gestation. In the placentome on Day 60 of gestation, in situ
      hybridization analysis evidenced bPRP-VII mRNA in binucleate cells. bPRP-VII gene
      produced a mature protein in mammalian cell expression system. Approximately
      29kDa protein was confirmed in this by the Western blot analysis with FLAG
      epitope tag. Expression profiles and localization were similar to those of bPRP
      I. Although the functional data remain to be examined, a new member of the bPRP
      VII gene was cloned. In addition to bPRP-I, bPRP-VII may take on an important
      functional role in implantation.

PMID- 15582597
TI  - An investigation into the role of Bcl-2 in neuroendocrine differentiation.
AB  - INTRODUCTION: In addition to its role in apoptosis suppression, Bcl-2 has been
      reported to be co-expressed with neuroendocrine markers in several tissues,
      leading to speculation that this oncoprotein may promote neuroendocrine
      differentiation. AIM: This study investigated whether Bcl-2 modulated
      neuroendocrine biopeptide expression. METHODS: Levels of chromogranin A, neurone
      specific enolase, protein gene peptide 9.5, pancreatic polypeptide, and the
      chromogranin-derived peptides, intervening peptide and vasostatin-1 were examined
      by immunocytochemistry in rat phaeochromocytoma (PC12) cell lines genetically
      engineered to over-express Bcl-2 and their mock-transfected controls. Intensity
      of fluorescence was graded using a semi-quantitative scale from (-) indicating
      negative expression to (+++) indicating intense positivity. RESULTS: Mann-Whitney
      U analysis indicated that no significant differences in expression existed
      between control and Bcl2 over-expressing cell lines for any of the six peptides
      examined. CONCLUSIONS: The results of this study do not support the hypothesis
      that Bcl-2 promotes the acquisition of a neuroendocrine phenotype.

PMID- 15582598
TI  - Influence of polymorphism of glutathione S-transferase M1 on systolic blood
      pressure of normotensive individuals.
AB  - Studies have indicated that systolic (SBP) and diastolic (DBP) blood pressure are
      multi-factorial traits and significantly heritable. The aims of the present study
      are to assess whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1)
      genotypes are associated with SBP and DBP of normotensive subjects and to
      ascertain whether the level of SBP and DBP given exposure to cigarette smoking is
      modified by the specific genetic polymorphisms of GSTM1 and GSTT1. This cross
      sectional study was conducted on 140 subjects (49 females and 91 males) (mean
      age+/-SD: 38.7+/-14.7). The genotypes were determined using a polymerase chain
      reaction based method. Individuals were stratified according to the mean values
      of DBP and SBP, lower than or maximally same as the mean value defines as group I
      and higher than the mean value defines as group II. The logistic regression
      analyses were used. The best models fitted by logistic regression analysis for
      variables were associated with SBP and DBP. For analysis the combination of
      genotypes, sex, and smoking behavior was used as qualitative variables, and age,
      body mass index (BMI), and heart rate were used as covariates. Combination of
      "present-GSTT1, null-GSTM1" genotype (OR=0.001, 95% CI=0.00-0.439, P=0.025),
      heart rate (OR=1.065, 95% CI=1.018-1.114, P=0.006), and interaction between BMI
      and combination of "present-GSTT1, null-GSTM1" (OR=1.319, 95% CI=1.058-1.644,
      P=0.014) was associated with SBP. There was no association between either
      combination genotypes of GSTs or interaction of genotypes and smoking behavior on
      DBP. The present results suggest that the GSTM1 gene is one of the candidate
      genes that alter the baseline of SBP in normotensive individuals.

PMID- 15582599
TI  - ErbB2 overexpression in mammary cells upregulates VEGF through the core promoter.
AB  - The angiogenic molecule, vascular endothelial growth factor (VEGF), is a critical
      regulator of normal and pathologic angiogenesis. ErbB2, an epidermal growth
      factor receptor family member whose overexpression in mammary tumors is
      correlated with poor patient prognosis, has been implicated as a positive
      modulator of VEGF expression. Mammary tumor cells overexpressing ErbB2 (NAFA
      cells) and a normal mouse mammary cell line (HC11) transfected with ErbB2
      expression vectors were used to study the effects of ErbB2 overexpression on VEGF
      regulation. We found that ErbB2 overexpression led to an increase in endogenous
      VEGF mRNA as well as ErbB3 protein levels in HC11 cells. Additionally, we
      determined that ErbB2 overexpression-mediated upregulation of VEGF involves at
      least two distinct promoter elements, one previously identified as the hypoxia
      responsive element and the other the core promoter region (-161 to -51bp), which
      is specifically controlled via two adjacent SP1 binding sites (-80 to -60bp).

PMID- 15582600
TI  - Light-dependent regulation of chlorophyll b biosynthesis in chlorophyllide a
      oxygenase overexpressing tobacco plants.
AB  - Chlorophyllide a oxygenase (CAO) that converts chlorophyllide a to chlorophyllide
      b was overexpressed in tobacco to increase chlorophyll (Chl) b biosynthesis and
      alter the Chl a/b ratio. Transgenic plants along with their wild-type cultivars
      were grown in low and high light intensities. In low light there was 20% increase
      in chlorophyll b contents in transgenic plants, which resulted in 16% reduction
      in the Chl a/b ratio. In high light, total Chl contents were 31% higher in
      transgenic plants than those of wild type. The increase in Chl a was 19% and that
      of Chl b was 72% leading to 31% decline of Chl a/b ratio. The increase in Chl b
      contents was accompanied by enhanced CAO expression that was highly pronounced in
      low light. As compared to low light, in high light Lhcb1 and Chl a/b transcripts
      abundance was significantly increased in transgenic plants suggesting a close
      relationship between Chl b synthesis and cab gene expression. However, there was
      a small increase in expression of LHCII proteins, which did not correspond to 72%
      increase in Chl b content in transgenic line, implying that LHCPII has the
      ability to bind more Chl b molecules.

PMID- 15582601
TI  - Curcumin for malaria therapy.
AB  - Malaria remains a major global health concern. New, inexpensive, and effective
      antimalarial agents are urgently needed. Here we show that curcumin, a
      polyphenolic organic molecule derived from turmeric, inhibits chloroquine
      resistant Plasmodium falciparum growth in culture in a dose dependent manner with
      an IC(50) of approximately 5 microM. Additionally, oral administration of
      curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces
      blood parasitemia by 80-90% and enhances their survival significantly. Thus,
      curcumin may represent a novel treatment for malarial infection.

PMID- 15582602
TI  - Prediction of mutation trend in hemagglutinins and neuraminidases from influenza
      A viruses by means of cross-impact analysis.
AB  - In this study, we use the cross-impact analysis to define the relationship among
      impact, mutation, and outbreak of bird flu. Then we use the distribution rank,
      which is developed by us over last several years, to quantify the mutations from
      amino acid sequences of 134 hemagglutinins and 97 neuraminidases. With the help
      of Bayesian equation, we calculate the probability of occurring of mutation in
      H5, H6, and H9 hemagglutinins, and N1 and N2 neuraminidases. Finally, we estimate
      the probability of occurring of mutation with different intensities of an impact.
      Although we have no means to predict an impact, which is severe enough to lead to
      the mutations in hemagglutinins and neuraminidases resulting in the outbreak of
      bird flu, we can in principle monitor the changes in distribution rank along the
      time course, and predict the trend of mutations, even to predict the degree of
      outbreak of bird flu.

PMID- 15582603
TI  - Inhibition of murine N1-acetylated polyamine oxidase by an acetylenic amine and
      the allenic amine, MDL 72527.
AB  - Murine N(1)-acetylated polyamine oxidase (mPAO) was treated with N,N'-bis-(prop-2
      ynyl)-1,4-diaminobutane, a poor substrate and inhibitor for the enzyme, with K(m)
      and K(i) values in the millimolar range. Apparently, its oxidation produces prop
      2-ynal, which reacts with amino acyl nucleophiles. Using a steady-state kinetic
      assay, four phases were identified, the first being the oxidation of the compound
      via Michealis-Menten-type kinetics. As prop-2-ynal accumulates, there is a
      biphasic reduction in the rate. This process leads to an mPAO form that is nearly
      inactive (fourth phase), but displays classical Michealis-Menten-type kinetics.
      The enzyme-bound flavin is not modified in this process. In contrast, micromolar
      concentrations of the MDL 72527 (N,N'-bis-[buta-2,3-dienyl]-1,4-diaminobutane)
      inhibited mPAO rapidly and completely. It inhibits by first binding tightly and
      apparently irreversibly, and then slowly converts to a species where the
      inhibitor is covalently bound to the N5-position of the flavin's isoalloxazine
      ring. The covalent adduct was identified as a flavocyanine.

PMID- 15582604
TI  - Subcellular localization and dynamics of MysPDZ (Myo18A) in live mammalian cells.
AB  - MysPDZ is an unconventional myosin belonging to the class XVIII myosin containing
      a KE (lysine and glutamine)-rich domain and a PDZ domain, which codistributes
      with actin fibers partially without any canonical actin binding sequence in its
      myosin head domain. Recently, we reported the identification of a novel isoform
      of MysPDZ lacking these domains and exhibiting subcellular localization and
      expression profile different from the original form of MysPDZ. In order to
      delineate domains directing the subcellular localization of MysPDZ, we performed
      co-immunoprecipitation experiments and image analyses using mutants of MysPDZ
      fused with enhanced yellow fluorescent protein. Co-immunoprecipitation analyses
      showed that MysPDZ can self-associate through its C-terminus coiled-coil domain
      and the KE-rich domain mediates the interaction with actin. We observed by image
      analyses that the codistribution with actin fibers and the localization in inner
      surface of cell membrane of MysPDZ are controlled by the KE-rich domain and the
      PDZ domain, respectively. Time lapse video microscopy showed that MysPDZ in the
      cytoplasm moves randomly and rapidly within short range and is allocated to a
      subcellular compartment without ATP hydrolysis by MysPDZ. This suggests that
      MysPDZ is a protein which is unlike most unconventional myosins. Our study
      uncovers a novel role of the KE-rich and PDZ domains in directing subcellular
      localization and also contributes to a better understanding of functional
      differences in MysPDZ isoforms.

PMID- 15582605
TI  - Negative regulation of adipogenesis from human mesenchymal stem cells by Jun N
      terminal kinase.
AB  - Human mesenchymal stem cells (hMSCs) are capable of differentiating into several
      cell types including adipocytes, osteoblasts, and chondrocytes, under appropriate
      culture conditions. We found that SP600125, an inhibitor of Jun N-terminal kinase
      (JNK), promoted adipogenesis whereas it repressed osteogenesis from hMSCs.
      SP600125 increased the expression of adipogenic transcription factors,
      CCAAT/enhancer-binding proteins alpha and beta as well as peroxisome proliferator
      activated receptor gamma2, which suggested that the chemical acted on the early
      steps of transcriptional regulatory cascade in adipogenesis. A gene reporter
      assay showed that SP600125 and a dominant negative JNK promoted a transcriptional
      activity dependent on the cAMP-response element (CRE). Thus, JNK represses
      adipogenesis from hMSCs probably by, at least in part, inhibiting the
      transactivating function of CRE-binding protein. Another action of JNK,
      phosphorylation at Ser(307) of insulin receptor substrate-1, was also predicted
      to contribute to the repression of adipogenesis.

PMID- 15582606
TI  - Cloning and characterization of mouse mTERF encoding a mitochondrial
      transcriptional termination factor.
AB  - We report here the identification and characterization of mouse mTERF encoding a
      mitochondrial transcription termination factor. A full-length mTERF cDNA has been
      isolated and the genomic organization of mTERF has been elucidated. The mouse
      mTERF gene containing two exons encodes a 380 residue protein with a strong
      homology to the mTERF-like proteins of human and other organisms, related to
      mitochondrial transcription termination. Northern blot analysis detected both 1.4
      and 5.4kb transcripts. The mouse mTERF 1.4kb transcript agreeing with the size of
      cDNA is predominately expressed in heart and liver, but at extremely low level in
      other tissues. In addition, a approximately 5.4kb transcript likely resulting
      from the retention of intron appears to express abundantly in heart and skeletal
      muscle, but at very low level in other tissues. Furthermore, immunofluorescence
      analysis of NIH3T3 cells expressing mTERF-GFP fusion protein demonstrated that
      the mouse mTERF localizes in mitochondrion. These observations suggest that the
      mouse mTERF is an evolutionarily conserved mitochondrial transcription
      termination factor, thereby promoting the termination of transcription in
      mitochondrial RNA.

PMID- 15582607
TI  - Genistein directly inhibits GLUT4-mediated glucose uptake in 3T3-L1 adipocytes.
AB  - The isoflavone-derivative genistein is commonly applied as an inhibitor of
      tyrosine kinases. In this report we analyze the effect of genistein on insulin
      stimulated glucose uptake in 3T3-L1 adipocytes. In these cells insulin-induced
      glucose uptake is primarily mediated by the GLUT4 glucose transporter. We
      observed that pre-treatment with genistein did not affect insulin-induced
      tyrosine kinase activity of the insulin receptor or activation of protein kinase
      B. On the other hand, genistein acted as a direct inhibitor of insulin-induced
      glucose uptake in 3T3-L1 adipocytes with an IC(50) of 20 microM. We conclude that
      apart from acting as a general tyrosine kinase inhibitor, genistein also affects
      the function of other proteins such as the GLUT4 transporter. These data suggest
      that caution must be applied when interpreting data on the involvement of
      tyrosine kinase activity in glucose uptake in 3T3-L1 adipocytes.

PMID- 15582608
TI  - Synthesis of N-unsubstituted, mono- and disubstituted carbohydrate-1-O-carbamates
      and their behaviour in glycoside syntheses.
AB  - The syntheses of 44 1-carbamates from six different 1-O-unprotected carbohydrate
      derivatives (compounds 1-6), representing typical protecting pattern in glycoside
      synthesis, are described. The carbamate function is N-unsubstituted (compounds 1b
      6b), mono- (compounds a: N-trichloroacetyl, c: N-monochloroacetyl, d: N-acetyl,
      e: N-ethyl, f: N-allyl, g: N-phenyl) or disubstituted (compounds h: imidazolyl,
      i: N-diethyl, j: N-diphenyl). Additionally, three N-chlorosulfonyl carbamates are
      synthesized and used as intermediates for the synthesis of N-unsubstituted
      compounds b. The accessibility of these compounds is described and compared. Some
      of the carbamates (1, 4, 5a-j) are used as model compounds for systematic
      investigations in glycoside syntheses. Selected experimental data (reaction
      conditions, anomeric ratios, rotation values, selected NMR data) are tabulated.

PMID- 15582609
TI  - Synthesis of aryl sialosides using Mitsunobu conditions.
AB  - Mitsunobu conditions for the efficient synthesis of aryl alpha/beta-sialosides
      were developed. An oxidative work-up procedure was employed to avoid a cumbersome
      chromatographic separation from the 2,3-dehydro derivative of sialic acid, which
      is formed as a side-product.

PMID- 15582610
TI  - A selective Sc(OTf)3-catalyzed trialkylsilyl ether to acetyl ester exchange
      reaction with beta-l-idopyranoside and 3,4-O-isopropylidene-beta-D
      galactopyranoside derivatives.
AB  - The selective silylation of monosaccharide building blocks is useful for
      preparing complex oligosaccharides. We now report that the diol, methyl
      (dimethylthexylsilyl 3-O-pivaloyl-beta-L-idopyranosyl)uronate, can be selectively
      silylated at the O-2 position by trialkylsilyl triflates. After protection of O
      4, the O-2 silyl group can be selectively replaced by acetate by taking advantage
      of a trialkylsilyl-acetate exchange reaction catalyzed by Sc(OTf)3 in the
      presence of acetic anhydride. The high O-2 selectivity is shown for triethylsilyl
      (TES), tert-butyldimethylsilyl (TBS), and triisopropylsilyl (TIPS). The selective
      cleavage reaction only worked well for TES and TBS derivatives. A selection of
      silyl triflates and silyl chlorides were used as silylating reagents with ethyl
      3,4-O-isopropylidene-1-thio-beta-D-galactopyranoside. In most cases, silylation
      afforded 2,6-di-O-silylated products in high yields. Studies on the cleavage
      reaction showed that only the primary silylated protecting groups were replaced
      by acetyl groups. This reaction worked with a variety of silyl protecting groups
      but not the tert-butyldiphenylsilyl (TBDPS) protecting group. Unfortunately, the
      1-thioethyl group was also sensitive to the Sc(OTf)3, leading in these conditions
      to alpha/beta mixtures of the 1-acetates, which compromised the synthetic utility
      of this reaction for these compounds. The sequence presented here is a useful
      synthetic route to differentially protected L-iduronic acid building blocks.

PMID- 15582611
TI  - Kinetics of substrate transglycosylation by glycoside hydrolase family 3 glucan
      (1-->3)-beta-glucosidase from the white-rot fungus Phanerochaete chrysosporium.
AB  - To elucidate the interaction between substrate inhibition and substrate
      transglycosylation of retaining glycoside hydrolases (GHs), a steady-state
      kinetic study was performed for the GH family 3 glucan (1-->3)-beta-glucosidase
      from the white-rot fungus Phanerochaete chrysosporium, using
      laminarioligosaccharides as substrates. When laminaribiose was incubated with the
      enzyme, a transglycosylation product was detected by thin-layer chromatography.
      The product was purified by size-exclusion chromatography, and was identified as
      a 6-O-glucosyl-laminaribiose (beta-D-Glcp-(1-->6)-beta-D-Glcp-(1-->3)-D-Glc) by
      1H NMR spectroscopy and electrospray ionization mass spectrometry analysis. In
      steady-state kinetic studies, an apparent decrease of laminaribiose hydrolysis
      was observed at high concentrations of the substrate, and the plots of glucose
      production versus substrate concentration were thus fitted to a modified
      Michaelis-Menten equation including hydrolytic and transglycosylation parameters
      (K(m), K(m2), k(cat), k(cat2)). The rate of 6-O-glucosyl-laminaribiose production
      estimated by high-performance anion-exchange chromatography coincided with the
      theoretical rate calculated using these parameters, clearly indicating that
      substrate inhibition of this enzyme is fully explained by substrate
      transglycosylation. Moreover, when K(m), k(cat), and affinity for glucosyl-enzyme
      intermediates (K(m2)) were estimated for laminarioligosaccharides (DP=3-5), the
      K(m) value of laminaribiose was approximately 5-9 times higher than those of the
      other oligosaccharides (DP=3-5), whereas the K(m2) values were independent of the
      DP of the substrates. The kinetics of transglycosylation by the enzyme could be
      well interpreted in terms of the subsite affinities estimated from the hydrolytic
      parameters (K(m) and k(cat)), and a possible mechanism of transglycosylation is
      proposed.

PMID- 15582612
TI  - Glycoconjugates for the recognition of Bacillus spores.
AB  - Carbohydrates act as ligands in many biological processes, including the folding
      and secretion of proteins, cell-cell recognition, adhesion, and sporulation in
      the Bacillus genus. Fluorescent-labeled disaccharide glycoconjugates have been
      applied to evaluate binding to bacterial spores assuming that the spore surface
      is covered with carbohydrates. This study has shown that specific recognition of
      bacterial spores is based on interactions between disaccharide glycoconjugates
      acting as ligands and monosaccharide units expressed on the exterior of bacterial
      spores. Using fluorophore-assisted carbohydrate electrophoresis (FACE),
      carbohydrates that are expressed on the exterior of the spores were enumerated.
      The findings have an impact on how to improve ligand selection, essential for
      sensor development. In addition, the findings provide new information for
      inhibition of bacterial spores, and in general, demonstrate how carbohydrates
      function as recognition signals in nature.

PMID- 15582613
TI  - Structure elucidation by NMR spectroscopy of a new acetylated saponin from
      Centratherum anthelminticum.
AB  - A new glycosylated triterpene has been isolated from the seeds of Centratherum
      anthelminticum, a medicinally important plant. The structural analysis of its
      acetylated derivative was performed by 1H, 13C NMR, 1H-1H COSY, HMQC, HMBC and
      DEPT spectroscopy. The saponin was shown to contain hederagenin and six sugar
      residues forming two glycosyl chains. The complete structure of the saponin was
      established as 3-O-[beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)
      alpha-L-arabinopyranosyl]-28-O-[beta-D-glucuronopyranosyl-(1-->4)-alpha-L
      rhamnopyranosyl-(1-->3)-beta-D-glucopyranosyl]-hederagenin.

PMID- 15582614
TI  - Isolation and characterization of two positional isomers of novel heterogeneous
      branched cyclomaltohexaoses (alpha-cyclodextrins) having a D-galactobiosyl
      residue on the side chain.
AB  - Transgalactosylated products, 2-O-alpha-D-galactobiosyl-cyclomaltohexaoses (alpha
      cyclodextrins, alphaCDs), were synthesized by alpha-galactosidase from coffee
      bean using melibiose and alphaCD as a donor substrate and an acceptor,
      respectively. Two positional isomers of 2-O-alpha-galactobiosyl-alphaCDs were
      isolated and purified by HPLC, and their structures were elucidated by FABMS and
      NMR spectroscopies, as well as by an enzymatic degradation method. The
      chromatographic behavior of these novel galactosylated alphaCDs was compared on
      three HPLC columns with different separation modes.

PMID- 15582615
TI  - Effect of carbohydrates on fructosyltransferase expression and distribution in
      Streptococcus mutans GS-5 biofilms.
AB  - Streptococcus mutans produces a fructosyltransferase (FTF) enzyme, which
      synthesizes fructan polymers from sucrose. Fructans contribute to the virulence
      of the biofilm by acting as binding sites for S. mutans adhesion and as
      extracellular nutrition reservoir for the oral bacteria. Antibodies raised
      against a recombinant S. mutans FTF were used to test the effect of glucose,
      fructose, and sucrose on FTF expression in S. mutans GS-5 biofilms. Biofilms
      formed in the presence of fructose and glucose showed a higher ratio of FTF
      compared to biofilms formed in the presence of sucrose. Confocal laser scanning
      microscopy images of S. mutans biofilms indicated a carbohydrate-dependent FTF
      distribution. The layer adjacent to the surface and those at the liquid interface
      displayed high amounts cell-free FTF with limited amount of bacteria while the in
      between layers demonstrated both cell-free FTF and cells expressing cell-surface
      FTF. Biofilm of S. mutans grown on hydroxyapatite surfaces expressed several FTF
      bands with molecular masses of 160, 125, 120, 100, and 50 kDa, as detected by
      using FTF specific antibodies. The results show that FTF expression and
      distribution in S. mutans GS-5 biofilms is carbohydrate regulated.

PMID- 15582616
TI  - Variations in the fibre repeat between samples of cellulose I from different
      sources.
AB  - A powder X-ray diffractometer was used to measure the fibre repeat in cellulose I
      with sufficient precision to detect variations between samples from different
      sources. The variations were correlated with the lateral dimensions of the
      crystallites and were attributed to different minimum-energy fibre repeats for
      chains in the interiors and on the surfaces of crystallites. Results were
      interpreted in terms of a model for internal mechanical stress in which the
      interior chains were under compression and the surface chains under tension to
      ensure identical fibre repeats for all chains. The model was used to extrapolate
      the fibre repeat to a value of 1.043 nm for a hypothetical, infinitely large
      crystal, and to 1.029 nm for a crystallite so narrow that all chains were exposed
      on surfaces.

PMID- 15582617
TI  - An efficient route to thioglycosides with the 2,3-anhydro-D-ribo stereochemistry.
AB  - An improved route for the synthesis of p-tolyl 2,3-anhydro-5-O-benzoyl-1-thio
      beta-D-ribofuranoside and its alpha anomer, which are important intermediates in
      the synthesis of alpha- and beta-D-arabinofuranosides, has been developed. The
      products are obtained in six steps from D-xylose in 39% overall yield.

PMID- 15582618
TI  - The structure of the core region of the lipopolysaccharide from Geobacter
      sulfurreducens.
AB  - The structure of the core part of the LPS from Geobacter sulfurreducens was
      analysed. The LPS contained no O-specific polysaccharide (O-side chain) and upon
      mild hydrolysis gave a core oligosaccharide, which was isolated by gel
      chromatography. It was studied by chemical methods, NMR and mass spectrometry,
      and the following structure was proposed. [carbohydrate structure: see text]
      where Q = 3-O-Me-alpha-L-QuiNAc-(1-->or H (approximately 3:2).

PMID- 15582619
TI  - Are consonant intervals music to their ears? Spontaneous acoustic preferences in
      a nonhuman primate.
AB  - Humans find some sounds more pleasing than others; such preferences may underlie
      our enjoyment of music. To gain insight into the evolutionary origins of these
      preferences, we explored whether they are present in other animals. We designed a
      novel method to measure the spontaneous sound preferences of cotton-top tamarins,
      a species that has been extensively tested for other perceptual abilities.
      Animals were placed in a V-shaped maze, and their position within the maze
      controlled their auditory environment. One sound was played when they were in one
      branch of the maze, and a different sound for the opposite branch; no food was
      delivered during testing. We used the proportion of time spent in each branch as
      a measure of preference. The first two experiments were designed as tests of our
      method. In Experiment 1, we used loud and soft white noise as stimuli; all
      animals spent most of their time on the side with soft noise. In Experiment 2,
      tamarins spent more time on the side playing species-specific feeding chirps than
      on the side playing species-specific distress calls. Together, these two
      experiments suggest that the method is effective, providing a spontaneous measure
      of preference. In Experiment 3, however, subjects showed no preference for
      consonant over dissonant intervals. Finally, tamarins showed no preference in
      Experiment 4 for a screeching sound (comparable to fingernails on a blackboard)
      over amplitude-matched white noise. In contrast, humans showed clear preferences
      for the consonant intervals of Experiment 3 and the white noise of Experiment 4
      using the same stimuli and a similar method. We conclude that tamarins'
      preferences differ qualitatively from those of humans. The preferences that
      support our capacity for music may, therefore, be unique among the primates, and
      could be music-specific adaptations.

PMID- 15582620
TI  - Central inhibition ability modulates attention-induced motion blindness.
AB  - Impaired motion perception can be induced in normal observers in a rapid serial
      visual presentation task. Essential for this effect is the presence of motion
      distractors prior to the motion target, and we proposed that this attention
      induced motion blindness results from high-level inhibition produced by the
      distractors. To investigate this, we compared the extent of the attention-induced
      motion blindness effect with performance on central inhibition tasks: Stroop
      colour naming and negative priming. A negative correlation between Stroop
      interference and motion performance reflected that low Stroop scores, indicative
      of strong inhibition ability, was associated with more severe impairments in
      motion perception. This association could not be explained by individual
      differences in fluid intelligence, task switching or response speed. Negative
      priming was not specifically associated with attention-induced motion blindness.
      The results confirm that attention can modulate motion perception and suggest
      that the processes involved may be shared with high-level cognitive abilities.

PMID- 15582621
TI  - Lateralization of object-shape information in semantic processing.
AB  - An experiment was conducted to examine whether perceptual information,
      specifically the shape of objects, is activated during semantic processing.
      Subjects judged whether a target word was related to a prime word. Prime-target
      pairs that were not associated, but whose referents had similar shapes (e.g.
      LADDER-RAILROAD) yielded longer "no" responses than unassociated prime-target
      pairs, suggesting that shape information had been activated. A visual-field
      manipulation showed that, in right-handed subjects, this effect was localized in
      the left hemisphere. This finding is consistent with behavioral, brain imaging,
      and lesion data, which suggest that object shape at the category level is
      represented in the left hemisphere.

PMID- 15582622
TI  - Listen to your mother! The role of talker familiarity in infant streaming.
AB  - Little is known about the acoustic cues infants might use to selectively attend
      to one talker in the presence of background noise. This study examined the role
      of talker familiarity as a possible cue. Infants either heard their own mothers
      (maternal-voice condition) or a different infant's mother (novel-voice condition)
      repeating isolated words while a female distracter voice spoke fluently in the
      background. Subsequently, infants heard passages produced by the target voice
      containing either the familiarized, target words or novel words. Infants in the
      maternal-voice condition listened significantly longer to the passages containing
      familiar words; infants in the novel-voice condition showed no preference. These
      results suggest that infants are able to separate the simultaneous speech of two
      women when one of the voices is highly familiar to them. However, infants seem to
      find separating the simultaneous speech of two unfamiliar women extremely
      difficult.

PMID- 15582623
TI  - The role of discourse context in the processing of a flexible word-order
      language.
AB  - On-line comprehension studies of flexible word-order languages find that
      noncanonical ('scrambled') structures induce more difficulty than canonical
      structures [e.g., Hyona & Hujanen, Q. J. Exp. Psychol. 50A (1997) 841-858], with
      this difference being attributed to the structural complexity/infrequency of
      these forms. However, by presenting sentences in isolation, most existing studies
      have not examined the extent to which processing patterns can be explained by
      discourse factors. In Finnish, an articleless flexible word-order language with
      canonical SVO order, word order can be used to encode the given/new distinctions:
      OVS marks the object as given and the subject as new; SVO is more flexible, being
      used in multiple contexts. Thus, the observed dispreference for noncanonical
      orders in previous work may arise from additional presuppositions needed to
      understand them out of context [cf. Crain & Steedman, Natural Language Parsing,
      (1985), 320-358]. Two experiments were conducted to examine these issues in
      Finnish. Experiment 1 used a self-paced reading task to show that the usual
      difficulty associated with noncanonical constructions is partially alleviated in
      the presence of appropriate discourse contexts. In Experiment 2, the eye gaze of
      listeners was tracked as they heard spoken descriptions of scenes, so as to test
      whether specific on-line referential processes are involved in SVO/OVS
      comprehension: Upon hearing an OV... sequence, Finnish listeners should expect
      the upcoming noun to be discourse-new, whereas an SV... sequence makes no such
      prediction. The results confirmed these predictions. As compared to SVO, OVS
      sentences showed anticipatory eye movements to a discourse-new referent at the
      second noun onset, even before participants had enough acoustic information to
      recognize this word. Our findings illustrate that in a flexible word-order
      language, a noncanonical order can result in anticipatory processes regarding the
      discourse status of a yet-to-be-heard constituent.

PMID- 15582624
TI  - Orientational manoeuvres in the dark: dissociating allocentric and egocentric
      influences on spatial memory.
AB  - Subjects in a darkroom saw an array of five phosphorescent objects on a circular
      table and, after a short delay, indicated which object had been moved. During the
      delay the subject, the table or a phosphorescent landmark external to the array
      was moved (a rotation about the centre of the table) either alone or together.
      The subject then had to indicate which one of the five objects had been moved. A
      fully factorial design was used to detect the use of three types of
      representations of object location: (i) visual snapshots; (ii) egocentric
      representations updated by self-motion; and (iii) representations relative to the
      external cue. Improved performance was seen whenever the test array was oriented
      consistently with any of these stored representations. The influence of
      representations (i) and (ii) replicates previous work. The influence of
      representation (iii) is a novel finding which implies that allocentric
      representations play a role in spatial memory, even over short distances and
      times. The effect of the external cue was greater when initially experienced as
      stable. Females out-performed males except when the array was consistent with
      self-motion but not visual snapshots. These results enable a simple egocentric
      model of spatial memory to be extended to address large-scale navigation,
      including the effects of allocentric knowledge, landmark stability and gender.

PMID- 15582625
TI  - Grammatical language impairment and the specificity of cognitive domains:
      relations between auditory and language abilities.
AB  - Grammatical-specific language impairment (G-SLI) in children, arguably, provides
      evidence for the existence of a specialised grammatical sub-system in the brain,
      necessary for normal language development. Some researchers challenge this,
      claiming that domain-general, low-level auditory deficits, particular to rapid
      processing, cause phonological deficits and thereby SLI. We investigate this
      possibility by testing the auditory discrimination abilities of G-SLI children
      for speech and non-speech sounds, at varying presentation rates, and controlling
      for the effects of age and language on performance. For non-speech formant
      transitions, 69% of the G-SLI children showed normal auditory processing, whereas
      for the same acoustic information in speech, only 31% did so. For rapidly
      presented tones, 46% of the G-SLI children performed normally. Auditory
      performance with speech and non-speech sounds differentiated the G-SLI children
      from their age-matched controls, whereas speed of processing did not. The G-SLI
      children evinced no relationship between their auditory and
      phonological/grammatical abilities. We found no consistent evidence that a
      deficit in processing rapid acoustic information causes or maintains G-SLI. The
      findings, from at least those G-SLI children who do not exhibit any auditory
      deficits, provide further evidence supporting the existence of a primary domain
      specific deficit underlying G-SLI.

PMID- 15582626
TI  - Action, verbal response and spatial reasoning.
AB  - Studies have shown that perception of distance, orientation and size can be
      dissociated from action tasks. The action system seems to possess more veridical,
      unbiased information than the perceptual/verbal system. The current study
      examines the nature of the distinction between action and verbal responses in a
      spatial reasoning task. Participants imagined themselves facing different
      orientations and either pointed to where other objects would be, or verbally
      reported their egocentric directions (e.g., "50 degrees to my left"). When using
      pointing responses, RT and error increased as a function of the angular disparity
      between the imagined heading and their actual heading. However, when using verbal
      responses, performance was not affected by angular disparity, suggesting that
      participants knew the direction of the targets from the imagined perspective but
      could not point to them directly. The verbal and action systems have
      fundamentally different information or processes rather than quantitatively
      different ones.

PMID- 15582627
TI  - Standardization for image characteristics in telemammography using genetic and
      nonlinear algorithms.
AB  - As the soft copy reading and computer assisted diagnosis (CAD) in mammography
      become more and more important, the standardization of digital images becomes
      paramount. Telemammography and telemedicine requires the standardization for
      image characteristics, such as image resolution, bit-depth and intensity
      response. Soft copy reading and CAD in mammography are both dependent on the
      characteristics of the source of the digital data, either direct digital
      mammography or digitized screen-film mammography. An algorithm developed on
      images from one database may not perform well as on images from another database
      (with a different digitization). In this paper, we describe two methods based on
      a genetic algorithm and a nonlinear algorithm for standardization of digitized
      and digital mammography. The proposed standardization techniques are based on
      geometric and intensity transformations that are discovered using a set of
      calibration images. A set of transformation algorithm is used to search for the
      best standardization.

PMID- 15582628
TI  - Quantification of the dynamic behavior over time of narrow-band components
      present in heart rate variability by means of the instantaneous amplitude and
      frequency.
AB  - The statistical properties of the time- and frequency-domain characteristics of
      heart rate variability are known to vary over time. A method is presented to
      compute the time-varying spectral contents of the characteristic narrow-band
      frequency components of heart rate variability by means of the instantaneous
      amplitude and frequency at an optimal time resolution. The instantaneous
      frequency may show oscillatory, but also irregular periods in time. An index of
      the instantaneous bandwidth is computed to discriminate between oscillatory and
      irregular periods and to correct the instantaneous amplitude and frequency for
      irregular periods.

PMID- 15582629
TI  - Simulation of pulmonary ventilation and its control by negative feedback.
AB  - The equivalent electronic circuit developed to simulate pulmonary ventilation is
      upgraded to incorporate homeostasis, i.e. a negative feedback loop. The latter
      can be made either inactive or active. In the former condition, only the
      immediate consequence of a disturbance shows up. In the latter condition,
      however, full homeostatic--sometimes very complex--response can be studied. The
      effects of three types of disturbances are studied in both conditions (i.e. open
      loop, closed loop): increased CO2 production, temporary apnoea, and of
      bronchoconstriction (in the whole lung or only in part of the lung). The effect
      of increased CO2 production is increase in pulmonary ventilation and increase in
      pCO2. The latter strongly depends on the feedback response. Temporary apnoea
      results in a transient increase in pCO2. However, if the time constant of the
      feedback loop is large enough, this type of disturbance results in a maintained
      periodic, Cheyne-Stokes-type breathing. Bronchoconstriction in 100% of the lung
      results in a decrease in tidal volume. If homeostasis is active this decrease is
      compensated by an increase in the inspiratory effort. However, if
      bronchoconstriction occurs only in 50% of the lung, inspiratory effort is greatly
      changed through inter-alveolar elastic interactions, giving rise to the so-called
      pendelluft.

PMID- 15582630
TI  - Hierarchical morphological design of immunoassay technology.
AB  - The paper describes a hierarchical design approach to an immunoassay. A
      morphology for an immunoassay technology is considered as a basis to generate
      system versions. A 5-stage technology is analyzed. The problem is: Find the best
      composite version for each stage while taking into account requirements
      (criteria) at each stage and compatibility between selected design alternatives
      at different stages. Hierarchical solving procedure consists of two parts: (a)
      multicriteria ranking of alternative versions at each stage (e.g., selection of
      Pareto-effective local decisions), (b) composition of the selected versions into
      a parallel-series composite system (technology). A realistic numerical example
      illustrates the approach.

PMID- 15582631
TI  - Automatic noise robust registration of radiographs for subtraction using
      strategic local correlation: an application to radiographs of dental implants.
AB  - Most of digital subtraction methods in dental radiography are based on
      registration using manual landmarks. We have developed an automatic registration
      method without using the manual selection of landmarks. By restricting a
      geometrical matching of images to a region of interest (ROI), we compare the
      cross-correlation coefficient only between the ROIs. The affine or perspective
      transform parameters satisfying maximum of cross-correlation between the local
      regions are searched iteratively by a fast searching strategy. The parameters are
      searched on the 14 scale image coarsely and then, the fine registration is
      performed on the original scale image. The developed method can match the images
      corrupted by Gaussian noise with the same accuracy for the images without any
      transform simulation. The registration accuracy of the perspective method shows a
      17% improvement over the manual method. The application of the developed method
      to radiographs of dental implants provides an automatic noise robust registration
      with high accuracy in almost real time.

PMID- 15582632
TI  - A fusion-based clinical decision support for disease diagnosis from endoscopic
      images.
AB  - This paper presents an intelligent decision support system designed on a decision
      fusion framework coupled with a priori knowledge base for abnormality detection
      from endoscopic images. Sub-decisions are made based on associated component
      feature sets derived from the endoscopic images and predefined algorithms, and
      subsequently fused to classify the patient state. Bayesian probability
      computations are employed to evaluate the accuracies of sub-decisions, which are
      utilized in estimating the probability of the fused decision. The overall
      detectability of abnormalities by using the proposed fusion approach is improved
      in terms of detection of true positive and true negative conditions when compared
      with corresponding results from individual methods.

PMID- 15582634
TI  - Cues for the identification of pain in nursing home residents.
AB  - The aim of this section of a larger study was to identify the range of cues from
      which pain was inferred for a sample of residents with various levels of
      cognitive impairment in 15 UK nursing homes. Sixty-five nursing home staff and 36
      informal carers of the 113 residents were interviewed. There was extensive use of
      body movements, facial expressions, and verbal and vocal cues and a considerable
      degree of interpretation of cues was used. There was little difference between
      the types of cue used by formal and informal carers, although informal carers
      tended to identify more of all types. There were differences in cues identified
      according to level of cognitive impairment, in particular, the interpretation of
      body movements. A simple model of the interaction between cognitive deficit, cue
      type and level of cue interpretation was proposed.

PMID- 15582635
TI  - Hand dermatitis among nurses in a newly developing region of Mainland China.
AB  - Although hand dermatitis (HD) is a common occupational problem for nurses
      worldwide; few, if any, epidemiological studies of this disease have been
      conducted in Mainland China. Therefore, we administered a previously validated
      questionnaire to 306 nurses from a large teaching hospital in Shijiazhuang city,
      Hebei province. A total of 282 replies were received (92.2%). The 12-month period
      prevalence of HD across hospital departments ranged from 14.3% to 23.8%, with an
      overall rate of 17.7%. Nurses with pre-existing atopic dermatitis were 5.3 times
      more likely to suffer from HD when compared to nurses without this condition (OR
      5.3, 95% CI 2.0-14.2, P = 0.0009). Overall, our study suggests that HD is less
      common among Chinese hospital nurses when compared to their counterparts around
      the world. The identification of atopic dermatitis as a significant HD risk
      factor was, however, consistent with previous research.

PMID- 15582636
TI  - Emotional adjustment and concerns of Korean mothers of premature infants.
AB  - This study describes the emotional adjustment and concerns of 50 Korean mothers
      of premature infants from hospitalization through six weeks after discharge. Five
      themes emerged: self-blame, concern about the infant, reluctance to express
      negatives, fear of stigmatizing responses to the infant by others, and delayed
      joy in mothering. Three Korean cultural beliefs influenced mothers' responses to
      premature birth: maternal responsibility for infant outcomes, negative thoughts
      can lead to negative consequences, and stigmatization of prematurity. Results
      identify specific ways caregivers in Korea and other countries can provide
      culturally appropriate support for Korean mothers experiencing a premature birth.

PMID- 15582637
TI  - The effects of reminiscence in promoting mental health of Taiwanese elderly.
AB  - This study examined the effects of reminiscence on four selected mental health
      indicators, including depressive symptoms, mood status, self-esteem, and self
      health perception of elderly people residing in community care facilities and at
      home. A longitudinal quasi-experimental design was conducted, using two
      equivalent groups for pre-post test and purposive sampling with random
      assignment. Each subject was administered pre- and post- tests at a 4 month
      interval but subjects in the experimental group underwent weekly intervention.
      Ninety-four subjects completed the study, with 48 in the control group and 46 in
      the experimental group. In the experimental group, a statistically significant
      difference (p = 0.041) was found between the pre-post tests on the dependent
      variable, depressive symptoms. However, no statistical significance was found in
      subjects' level of mood status, self-esteem, and self-health perception after the
      intervention in the experimental group, but slightly improvement was found.
      Reminiscence not only supports depression of the elderly but also empower nurses
      to become proactive in their daily nursing care activities.

PMID- 15582638
TI  - The effect of various combinations of turning and pressure reducing devices on
      the incidence of pressure ulcers.
AB  - BACKGROUND: Turning is considered to be an effective way of preventing pressure
      ulcers, however almost no research has been undertaken on this method. AIM: The
      aim of the study was to investigate the effect of four different preventative
      regimes involving either frequent turning (2, 3 hourly) or the use of a pressure
      reducing mattress in combination with less frequent turning (4, 6 hourly).
      SUBJECTS: 838 geriatric nursing home patients participated in the study. METHODS:
      During 28 days, four different turning schemes were used: turning every 2 h on a
      standard institutional (SI) mattress (n = 65), turning every 3 h on a SI mattress
      (n = 65), turning every 4 h on a viscoelastic foam (VE) mattress (n = 67), and
      turning every 6h on a VE mattress (n = 65). The remaining patients (n = 576)
      received standard preventive care. MAIN RESULTS: The incidence of non-blanchable
      erythema (34.8-38.1%) was not different between the groups. The incidence of
      grade II and higher pressure ulcers in the 4h interval group was 3.0%, compared
      with incidence figures in the other groups varying between 14.3% and 24.1%.
      CONCLUSIONS: Turning every 4 h on a VE mattress resulted in a significant
      reduction in the number of pressure ulcer lesions and makes turning a feasible
      preventive method in terms of effort and cost.

PMID- 15582639
TI  - An evaluation of the first year of family health nursing practice in Scotland.
AB  - Scotland has led enactment of the new World Health Organisation (Europe) Family
      Health Nurse (FHN) concept. This paper presents research which evaluated the
      initial operation and impact of the role in remote and rural regions of Scotland.
      Through use of a multiplex research design informed by ideas from realistic
      evaluation, fourth generation evaluation and case study research, an initial
      typology of practice was constructed. The new FHN role typically supplemented,
      rather than supplanted, pre-existing community nursing services. Implications
      arising from key findings are discussed in relation to Scottish, UK and European
      nursing and primary care perspectives.

PMID- 15582640
TI  - Staff experiences in implementing guidelines for Kangaroo Mother Care--a
      qualitative study.
AB  - The aim of this study was to investigate staff experiences in implementing
      guidelines for Kangaroo Mother Care in neonatal care. The study was part of a
      randomized controlled trial, the overall goal of which was to assess the impact
      of external facilitation. A total of eight focus group interviews were held at
      two intervention and two control units. The establishment of a change team to
      implement the guideline resulted in activities that impacted staff behaviour,
      which in turn was perceived to influence patients' well-being. The guideline and
      contextual factors, such as leadership and staff colleagues' attitudes, were of
      significant importance in that process. The study intervention--facilitation-
      promoted implementation activities and was highly appreciated by the change
      teams. However, reviewing the development of events at one of the control units,
      the provided facilitation appeared to be no more effective than an improvement
      focused organizational culture in which the nurse manager was actively involved
      in the change process. Overall, learning and behaviour change seemed to be a
      social phenomenon, something that greatly benefited from people's interaction
      with one another.

PMID- 15582641
TI  - Relationships between patient dependency, nursing workload and quality.
AB  - The nature and value of dependency-acuity-quality (DAQ) demand-side nursing
      workforce planning methods are set in the context of nursing workforce planning
      and development. Extensive DAQ data from one of the largest UK nursing workforce
      studies (347 wards) involving 64 high-quality and 62 low-quality hospital wards,
      are reconsidered in a workload and quality context. Results generate new
      insights; for example, poor quality care is more likely to be a feature of larger
      wards with fluctuating workloads than smaller wards with consistently high
      workloads owing to inflexible nurse staffing. Nursing activity and staffing
      differences between high- and low-quality wards are highlighted. Recommendations
      are made to improve nursing management and practice as well as the next phase of
      DAQ studies.

PMID- 15582642
TI  - The experience of a good day: a phenomenological study to explain a good day as
      experienced by a newly qualified RN.
AB  - The main aim of this study was to provide an explanation of the newly qualified
      nurse's experience and description of a good day. Secondly it sought to provide
      an explanation of how a good day made them feel about nursing. By identifying the
      main components of a good day and what positively effects the experience of a
      working day for a newly qualified nurse, it may be possible to move towards an
      increase in the occurrence of the components and emulation of a good day. While
      there is evidence to suggest that positive experiences within nursing increase
      job satisfaction and aid retention to the profession, the experience of a good
      day and what constitutes a good day for a newly qualified nurse has not been
      explored. The main components of a good day have not been identified and no work
      has been carried out to ascertain how these days make nurses feel about their
      chosen career. The aims of the study lent themselves to a phenomenological
      descriptive approach to research, the objective of which is identification of the
      essence of behaviour. Eight newly qualified nurses agreed to take part in the
      research. Each participant was interviewed twice, and in addition one group
      interview was arranged to clarify themes. The interviews, which were audio taped,
      were informal allowing the participants to answer in an open and unstructured
      manner. Once completed, all the tapes were transcribed and immersion and analysis
      of the data led to 5 themes naturally emerging as the components of a good day.
      The identified themes were, doing something well, good relationships with
      patients, feeling that you've achieved something, getting the work done and you
      need team work. In addition, although not a theme of a good day but of great
      importance was the description of 'that wonderful feeling at the end of a good
      day'. These themes contributed to feelings of job satisfaction and the pleasure
      of nursing. More specifically the concept of knowing the patient both from a
      personal level and knowing about their care and condition has been identified as
      a main component of a good day. This knowing the patient had a knock on effect in
      that when this was part of the day it was easier to prioritise and get the work
      done. These nurses were striving to develop a level of care and competency and,
      unlike expert nurses, did not have vast experience and knowledge to underpin
      their actions. They need to ensure that all levels of knowledge are addressed
      before they can carry out care. Additionally the team dynamics and the way the
      team work together had a significant effect on the day.

PMID- 15582643
TI  - Illuminating continuing professional education: unpacking the black box.
AB  - This paper reports on a longitudinal study of continuing professional education
      (CPE) in nursing using a case study approach operationalised within an
      illuminative evaluation model. Using a short focussed programme as an
      instrumental case study, the project gathered data from three major groups of
      stakeholders over an 18 month period in order to explore the context within which
      CPE operates, and to highlight those factors which appear to influence the
      outcomes of CPE over time. Data were collected using documentary analysis and in
      depth semi-structured interviews with educators, students on the programme (the
      ENB 941), and their managers. The latter two groups were interviewed at four
      points in time (prior to the course, immediately post course, 6 and 12 months
      post course). Data analysis revealed that a complex set of factors interact to
      influence the outcomes of CPE, including the nature of the selection process,
      students' expectations of the programme, the nature of the educational
      experience, and the receptivity of the practice environment to change. This paper
      identifies those factors that shape the outcomes of CPE and considers their
      implications for policy and practice.

PMID- 15582644
TI  - Post-acute intermediate care in nursing-led units: a systematic review of
      effectiveness.
AB  - OBJECTIVE: In order to determine whether post-acute intermediate care in nursing
      led inpatient units (NLUs) is effective in preparing patients for discharge from
      hospital we conducted a systematic review of the evidence. REVIEW METHODS: The
      Cochrane Library, Effective Practice and Organisation of Care specialist
      register, Medline, Cinahl, Embase, British Nursing Index and the HMIC databases
      were searched for all available dates up to mid-2003. The science and social
      science citation indices were searched for papers that cited key works. Authors
      of papers were asked to identify additional research. Randomised controlled
      trials, controlled clinical trials, controlled before and after studies and
      interrupted time-series designs that compared the NLU to usual post-acute
      inpatient care for adults were included in the review. Studies were assessed for
      quality. Statistical meta-analysis on the results of controlled trials was
      performed. Sensitivity analyses were conducted to determine the impact of
      methodological quality on conclusions. OUTCOMES: Outcomes considered were
      mortality, institutionalisation after discharge, functional status early
      readmission, length of inpatient stay and cost. RESULTS: Nine random or quasi
      random controlled trials involving 1669 patients were reviewed. Quality was
      variable. The mean age of patients in all studies was over 70 years. There was no
      statistically significant difference in inpatient mortality between NLU and usual
      inpatient care (OR 1.10, 95% CI 0.56-2.16). The NLU was associated with reduced
      odds of discharge to institutional care (OR 0.44 95% CI 0.22-0.89), better
      functional status at discharge (SMD 0.37, 95% CI 0.20-0.54) and reduced odds of
      early readmission (OR 0.52 95% CI 0.34-0.80). Length of stay until discharge home
      was increased by 5.13 days (WMD) (95% CI-0.5-10.76 days). At longest follow up (3
      6 months) there was no statistically significant difference in the proportion of
      patients in institutional care (OR 0.97, 95% CI 0.60-1.58). The results were not
      generally sensitive to study quality. CONCLUSIONS: The NLU successfully functions
      as a form of intermediate care, so far there is no evidence of adverse outcome
      from the lower level of routine medical care. However, more research is required
      to confirm safety. Patients discharged from NLUs have higher levels of function
      although it is unclear if the benefit is simply a product of an increased stay.
      There is no evidence of benefit over the longer term.

PMID- 15582645
TI  - Dose-dependent transitions in mechanisms of toxicity.
AB  - Scientists and decision makers from all sectors agree that risk assessments
      should be based on the best available science. Several years ago, the Health and
      Environmental Sciences Institute (HESI), a global branch of the International
      Life Sciences Institute (ILSI), identified the need for better scientific
      understanding of dose-dependent transitions in mechanisms of toxicity as one
      avenue by which the best and latest science can be integrated into the decision
      making process. In July 2001, the HESI Project Committee on Dose-Dependent
      Transitions in Mechanisms of Toxicity established a group of academic,
      government, and industry scientists to engage in active technical discourse on
      the issue of dose-dependent transitions in mechanisms of toxicity. Over the next
      18 months, case studies were examined. These case studies included acetaminophen,
      butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, the
      peroxisome proliferator-activated receptor, progesterone/hydroxyflutamide,
      propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc
      (Slikker, W., Jr., Andersen, M.E., Bogdanffy, M.S., Bus, J.S., Cohen, S.D.,
      Conolly, R.B., David, R.M., Doerrer, N.G., Dorman, D.C., Gaylor, D.W., Hattis,
      D., Rogers, J.M., Setzer, R.W., Swenberg, J.A., Wallace, K., 2004. Dose-dependent
      transitions in mechanisms of toxicity: case studies. Toxicol. Appl. Pharmacol.
      201(3), 226-294 (this issue)). The HESI Project Committee sponsored two technical
      workshops in 2003. The first of these workshops took place on February 12-13,
      2003, and was co-sponsored by the Agency for Toxic Substances and Disease
      Registry, the American Chemistry Council, the National Institute of Environmental
      Health Sciences, the Society of Toxicology, and the U.S. Environmental Protection
      Agency. Additional support was provided by Health Canada. Invited experts from
      government, academia, and industry provided scientific perspectives and
      recommendations at the workshop. The purpose of the workshop was to examine
      approaches to dose-response analysis, learn from the case study examples, and
      gather feedback from invited participants on the impact of dose-dependent
      transitions on the risk assessment process. The second forum consisted of a
      workshop in March 2003 at the Society of Toxicology Annual Meeting in Salt Lake
      City, UT. This paper addresses the issues discussed at both workshops, and
      presents the consensus conclusions drawn by expert participants.

PMID- 15582646
TI  - Dose-dependent transitions in mechanisms of toxicity: case studies.
AB  - Experience with dose response and mechanisms of toxicity has shown that multiple
      mechanisms may exist for a single agent along the continuum of the full dose
      response curve. It is highly likely that critical, limiting steps in any given
      mechanistic pathway may become overwhelmed with increasing exposures, signaling
      the emergence of new modalities of toxic tissue injury at these higher doses.
      Therefore, dose-dependent transitions in principal mechanisms of toxicity may
      occur, and could have significant impact on the interpretation of reference data
      sets for risk assessment. To illustrate the existence of dose-dependent
      transitions in mechanisms of toxicity, a group of academic, government, and
      industry scientists, formed under the leadership of the ILSI Health and
      Environmental Sciences Institute (HESI), developed a series of case studies.
      These case studies included acetaminophen, butadiene, ethylene glycol,
      formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated
      receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate,
      vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis
      for technical discourse at two scientific workshops in 2003.

PMID- 15582647
TI  - Determination of murine fetal Cyp1a1 and 1b1 expression by real-time fluorescence
      reverse transcription-polymerase chain reaction.
AB  - We describe the application of quantitative RT-PCR methodology to study
      expression of Cyp1a1 and 1b1 in murine fetal tissue. We applied real-time PCR
      using the fluorescent dye, SYBR Green, to establish a very reliable, sensitive,
      specific, inexpensive, and rapid assay that was linear over a wide dynamic range
      of starting target gene copy number. The main point of this paper is to provide a
      detailed description of how to optimize real-time reverse transcription
      polymerase chain reaction (RT-PCR) assays and, most importantly, to provide
      solutions for some of the commonly observed problems encountered when employing
      quantitative RT-PCR methods. We establish that use of SYBR Green for detection of
      PCR products was a powerful and reliable tool in our investigation of Cyp gene
      expression in murine fetal tissues, and demonstrate the kinetics of induction of
      Cyp1a1 and 1b1 in crosses between C57BL/6 and Balb/c mice. In addition, we
      demonstrate for the first time the induction of Cyp1b1 RNA expression in fetal
      lung and liver tissues following in utero exposure to 3-methylcholanthrene (MC),
      a polycyclic aromatic hydrocarbon. This assay for Cyp1a1 and 1b1 expression could
      be utilized equally well to detect other genes of interest in a variety of
      toxicological investigations.

PMID- 15582648
TI  - Antioxidant and antimutagenic activity of N-(2-carboxyethyl)chitosan.
AB  - The antioxidant and antimutagenic activities of the novel carboxyethyl
      derivatives of chitosan with three different degrees of substitution have been
      assayed in vitro in the unicellular flagellate Euglena gracilis subjected to the
      action of genotoxic agents acridine orange and ofloxacin. It has been
      demonstrated that chitosan derivatives exhibit concentration-dependent protective
      antigenotoxic activity against both mutagens. It is suggested that different
      mechanisms may be involved in its protective action--antioxidant activity in case
      of ofloxacin-induced DNA damage, as well as possible interaction with the cell
      membrane that prevents acridine orange from reaching the genetic compartments and
      subsequent damaging DNA through intercalative binding. Direct adsorption of
      acridine orange on chitosan derivatives was ruled out as a possible mechanism of
      protection on the basis of spectrophotometric measurements. Dependence of the
      antimutagenic properties of the studied chitosan derivatives on the degree of
      substitution was reversed in experiments involving acridine orange and ofloxacin,
      which also indicated different mechanisms of protection involved in these two
      cases.

PMID- 15582649
TI  - Functional comparison of the transposition core machineries of phage Mu and
      Haemophilus influenzae Mu-like prophage Hin-Mu reveals interchangeable
      components.
AB  - Bacteriophage Mu uses DNA transposition for propagation and is a model for
      transposition studies in general. Recent identification of Mu-like prophages
      within bacterial genomes offers new material for evolutionary and comparative
      functional studies. One such prophage, Hin-Mu of Haemophilus influenzae Rd, was
      studied for its transpositional properties. The components of its transposition
      core machinery, the encoded transposase (MuA(Hin)) and the transposase binding
      sites, were evaluated for functional properties by sequence comparisons and DNase
      I footprinting. Transpositional activity of Hin-Mu was examined by in vitro
      assays directly assessing the assembly and catalytic function of the
      transposition core machinery. The Hin-Mu components readily assembled
      catalytically competent protein-DNA complexes, transpososomes. Thus, Hin-Mu
      encodes a functional transposase and contains critical transposase binding sites.
      Despite marked sequence differences, components of the Hin-Mu and Mu
      transposition core machineries are partially interchangeable, reflecting both
      conservation and flexibility in the functionally important regions within the
      transpososome structure.

PMID- 15582650
TI  - Modified HIV envelope proteins with enhanced binding to neutralizing monoclonal
      antibodies.
AB  - The target for neutralizing antibodies against human immunodeficiency virus (HIV)
      is the trimeric Env protein on the native virion. Conserved neutralizing epitopes
      of receptor binding sites are located in the recessed core of the Env protein,
      partially masked by glycosylations and variable loops. In this study, we have
      investigated the effects of modifications of the HIV Env protein by glycosylation
      site mutations, deletions of variable loops, or combinations of both types of
      mutations on their protein functions and reactivities with neutralizing
      antibodies. Modified Env proteins were expressed in insect or mammalian cells,
      and their reactivity with epitope-specific broadly neutralizing monoclonal
      antibodies (Mabs) was determined by flow cytometry. A unique mutant designated 3G
      with mutations in three glycosylation motifs within the V3/C3 domains surrounding
      the CD4 binding site showed higher levels of binding to most broadly neutralizing
      Mabs (b12 and 2F5) in both insect and mammalian expression systems. Mutants with
      a deletion of both V1 and V2 loop domains or with a unique combination of both
      types of mutations also bound to most neutralizing Mabs at higher levels compared
      to the wild-type control. Most mutants maintained the ability to bind CD4 and to
      induce syncytium formation at similar or higher levels as compared to that of the
      wild-type Env protein, except for a mutant with a combination of variable loop
      deletions and deglycosylation mutations. Our study suggests that modified HIV Env
      proteins with reduced glycosylation in domains surrounding the CD4 binding site
      or variable loop-deleted mutants expose important neutralizing epitopes at higher
      levels than wild type and may provide novel vaccine immunogens.

PMID- 15582651
TI  - Analysis of the neutralizing antibody response elicited in rabbits by repeated
      inoculation with trimeric HIV-1 envelope glycoproteins.
AB  - The elicitation of broadly neutralizing antibodies directed against the human
      immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, gp120 and gp41,
      remains a major challenge. Attempts to utilize monomeric gp120 as an immunogen to
      elicit high titers of neutralizing antibodies have been disappointing. Envelope
      glycoprotein constructs that better reflect the trimeric structure of the
      functional envelope spike have exhibited improved immunogenicity compared with
      monomeric gp120. We have described soluble gp140 ectodomain constructs with a
      heterologous trimerization motif; these have previously been shown to elicit
      antibodies in mice that were able to neutralize a number of HIV-1 isolates, among
      them primary isolate viruses. Recently, solid-phase proteoliposomes retaining the
      envelope glycoproteins as trimeric spikes in a physiologic membrane setting have
      been described. Here, we compare the immunogenic properties of these two trimeric
      envelope glycoprotein formulations and monomeric gp120 in rabbits. Both trimeric
      envelope glycoprotein preparations generated neutralizing antibodies more
      effectively than gp120. In contrast to monomeric gp120, the trimeric envelope
      glycoproteins elicited neutralizing antibodies with some breadth of
      neutralization. Furthermore, repeated boosting with the soluble trimeric
      formulations resulted in an increase in potency that allowed neutralization of a
      subset of neutralization-resistant HIV-1 primary isolates. We demonstrate that
      the neutralization is concentration-dependent, is mediated by serum IgG and that
      the major portion of the neutralizing activity is not directed against the gp120
      V3 loop. Thus, mimics of the trimeric envelope glycoprotein spike described here
      elicit HIV-1-neutralizing antibodies that could contribute to a protective immune
      response and provide platforms for further modifications to improve the
      efficiency of this process.

PMID- 15582652
TI  - A DNA-launched reverse genetics system for porcine reproductive and respiratory
      syndrome virus reveals that homodimerization of the nucleocapsid protein is
      essential for virus infectivity.
AB  - Reverse genetic systems were developed for a highly virulent 'atypical' porcine
      reproductive and respiratory syndrome virus (PRRSV). The full-length genome of
      15395 nucleotides was assembled as a single cDNA clone and placed under either
      the prokaryotic T7 or eukaryotic CMV promoter. Transfection of cells with the RNA
      transcripts or the DNA clone induced cytopathic effects and produced infectious
      progeny. The reconstituted virus was stable and grew to the titer of the parental
      virus in cells. Upon infection, pigs produced clinical signs and lung pathology
      typical for PRRSV and induced viremia and specific antibodies. Previously, we
      showed that the PRRSV nucleocapsid (N) protein forms homodimers via both
      noncovalent and covalent interactions and that cysteine at position 23 is
      responsible for the covalent interaction. The functional significance of
      cysteines of N for PRRSV infectivity was assessed using the infectious cDNA
      clone. Each cysteine of N at positions 23, 75, and 90 was replaced with serine
      and the individual mutation was incorporated into the cDNA clone such that three
      independent cysteine mutants were constructed. When transfected, the wild type
      and C75S clones induced cytopathic effects and produced infectious virus with
      indistinguishable plaque morphology. In contrast, the C23S mutation completely
      abolished infectivity of the clone, indicating that C23-mediated N protein
      homodimerization plays a critical role in PRRSV infectivity. Unexpectedly, the
      C90S mutation also appeared to be lethal for virus infectivity. Genome
      replication and mRNA transcription were both positive for the replication
      defective C23S and C90S mutants. The data suggest that, in addition to
      homodimerization, the PRRSV N protein may also undergo heterodimerization with
      another structural protein using cysteine 90 and that the N protein
      heterodimerization is essential for PRRSV infectivity.

PMID- 15582653
TI  - Thogoto virus ML protein suppresses IRF3 function.
AB  - The Thogoto virus (THOV) is a member of the family Orthomyxoviridae. It prevents
      induction of alpha/beta interferons (IFN) in cell culture and in vivo via the
      action of the viral ML protein. Phenotypically, the effect of THOV ML resembles
      that of the NS1 protein of influenza A virus (FLUAV) in that it blocks the
      expression of IFN genes. IFN expression depends on IFN regulatory factor 3
      (IRF3). Upon activation, IRF3 forms homodimers and accumulates in the nucleus
      where it binds the transcriptional coactivator CREB-binding protein (CBP). Here,
      we show that expression of ML blocked the transcriptional activity of IRF3 after
      stimulation by virus infection. Further biochemical analysis revealed that ML
      acts by blocking IRF3 dimerization and association with CBP. Surprisingly,
      however, ML did not interfere with the nuclear transport of IRF3. Thus, the
      action of ML differs strikingly from that of FLUAV NS1 that prevents IFN
      induction by retaining IRF3 in the cytoplasm.

PMID- 15582654
TI  - Cooperativity of actin and microtubule elements during replication of respiratory
      syncytial virus.
AB  - Many paramyxoviruses appear to require cytoskeletal elements for particular steps
      in the virus life cycle. Measles virus and Sendai virus exhibit a requirement for
      microtubules in replication in vitro, whereas parainfluenza virus type 3 and RSV
      require actin for replication. To further elucidate the role of cytoskeletal
      function and rearrangement in the viral life cycle of RSV, we investigated the
      efficiency of virus entry, transcription, replication, and budding in the
      presence of a variety of pharmacological agents that stabilize or depolymerize
      actin or microtubules. We found that alteration of microtubule or actin function
      resulted in blocks at entry, formation of cell-associated virus, virus release,
      local cell-to-cell spread, and syncytium formation. Actin and microtubules act in
      cooperation to facilitate replication of RSV, although microtubules play a
      dominant role in the formation of cell-associated virus while actin plays a more
      prominent role in virus release.

PMID- 15582655
TI  - Strong cellular and humoral anti-HIV Env immune responses induced by a
      heterologous rhabdoviral prime-boost approach.
AB  - Recombinant rhabdovirus vectors expressing human immunodeficiency virus (HIV)
      and/or simian immunodeficiency virus (SIV) proteins have been shown to induce
      strong immune responses in mice and rhesus macaques. However, the finding that
      such responses protect rhesus macaques from AIDS-like disease but not from
      infection indicates that further improvements for these vectors are needed. Here,
      we designed a prime-boost schedule consisting of a rabies virus (RV) vaccine
      strain and a recombinant vesicular stomatitis virus (VSV) both expressing HIV
      Envelope (Env). Mice were primed and boosted with the two vaccine vehicles by
      different routes and in different combinations. Mucosal and systemic humoral
      responses were assessed using enzyme linked immunosorbent assay (ELISA) while the
      cellular immune response was determined by an IFN-gamma ELISPOT assay. We found
      that an immunization combination of RV and VSV elicited the highest titers of
      anti-Env antibodies and the greatest amount of Env-specific IFN-gamma secreting
      cells pre- and post-challenge with a recombinant vaccinia virus expressing
      HIV(89.6) Env. Furthermore, intramuscular immunization did not induce antigen
      specific mucosal antibodies while intranasal inoculation stimulated vector
      specific IgA antibodies in vaginal washings and serum. Our results show that it
      is feasible to elicit robust cellular and humoral anti-HIV responses using two
      different live attenuated Rhabdovirus vectors to sequentially prime and boost.

PMID- 15582656
TI  - Evidence for a direct interaction between HSV-1 ICP27 and ICP8 proteins.
AB  - Herpes simplex virus 1 (HSV-1) ICP27 and ICP8 proteins have both been implicated
      in the transcription of late genes and regulation of viral gene expression. We
      showed previously that ICP27 and ICP8 associate with the RNAP II holoenzyme (Zhou
      and Knipe, J. Virol. 76, 5893-5904). Here, we demonstrate that ICP27 and ICP8
      coprecipitate from lysates of HSV-1-infected HEp2 cells and from lysates of
      insect cells expressing ICP27 and ICP8, the latter being in the absence of other
      HSV-1 proteins. By expressing and purifying hexahistidine-tagged ICP8 (His-ICP8)
      and maltose binding protein (MBP)-tagged ICP27 (MBP-27) proteins and performing
      in vitro immunoprecipitation and pull-down assays, we also demonstrate that ICP27
      and ICP8 coprecipitate in the absence of other viral or cellular proteins. Taken
      together, these data provide evidence that ICP27 and ICP8 interact directly in
      vitro and in infected cells. We hypothesize that the ICP27-ICP8 interaction plays
      a role in the stimulation of late gene transcription.

PMID- 15582657
TI  - Amphotericin-B-mediated reactivation of latent HIV-1 infection.
AB  - To date, attempts to eliminate HIV-1 infection from its latent reservoirs, a
      prerequisite for the development of a curative treatment strategy for HIV-1
      infection, have been unsuccessful. We demonstrate that the FDA approved
      antifungal agent amphotericin B efficiently reactivates HIV-1 infection in
      THP89GFP cells, a model of HIV-1 latency in macrophages. Although amphotericin B
      does not directly reactivate latent HIV-1 infection in T cells (e.g., J89GFP),
      amphotericin-B-stimulated macrophages (THP89GFP cells or primary macrophages)
      when cocultured with J89GFP cells can induce HIV-1 reactivation in these cells in
      trans. Because of the close proximity of antigen presenting macrophages and T
      cells in the primary lymphoid organs, such interaction between antigen presenting
      macrophages and T cells are frequent, and it seems reasonable to assume that
      trans-reactivation strategies hold promise to also reactivate latent HIV-1
      infection in vivo.

PMID- 15582658
TI  - A map of the diversity of RNA3 recombinants appearing in plants infected with
      Cucumber mosaic virus and Tomato aspermy virus.
AB  - In order to better understand the role of recombination in creating the diversity
      of viral genomes that is acted on by selection, we have studied in detail the
      population of recombinant RNA3 molecules occurring in tobacco plants coinfected
      with wild-type strains of cucumber mosaic virus (CMV) and tomato aspermy virus
      (TAV) under conditions of minimal selection pressure. Recombinant RNA3s were
      observed in 9.6% of the samples. Precise homologous recombination predominated
      since it was observed at 28 different sites, primarily in six hot spots.
      Imprecise homologous recombination was observed at two sites, particularly within
      a GU repeat in the 5' noncoding region. Seven of the eight aberrant homologous
      recombination sites observed were clustered in the 3' noncoding region. These
      results have implications on the role of recombination in host adaptation and
      virus evolution. They also provide essential baseline information for
      understanding the potential epidemiological impact of recombination in transgenic
      plants expressing viral sequences.

PMID- 15582659
TI  - Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA
      vaccine.
AB  - The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein
      for the formation of the helical nucleocapsid during virion assembly. This
      protein is believed to be more conserved than other proteins of the virus, such
      as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was
      expressed in Escherichia coli DH5alpha and identified with pooled sera from
      patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full
      length N gene of SARS-CoV, was constructed. Expression of the N protein was
      observed in COS1 cells following transfection with pCI-N. The immune responses
      induced by intramuscular immunization with pCI-N were evaluated in a murine
      model. Serum anti-N immunoglobulins and splenocytes proliferative responses
      against N protein were observed in immunized BALB/c mice. The major
      immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and
      stimulated splenocytes secreted high levels of gamma interferon and IL-2 in
      response to N protein. More importantly, the immunized mice produced strong
      delayed-type hypersensitivity (DTH) and CD8(+) CTL responses to N protein. The
      study shows that N protein of SARS-CoV not only is an important B cell immunogen,
      but also can elicit broad-based cellular immune responses. The results indicate
      that the N protein may be of potential value in vaccine development for specific
      prophylaxis and treatment against SARS.

PMID- 15582660
TI  - Prediction of functional class of novel viral proteins by a statistical learning
      method irrespective of sequence similarity.
AB  - The function of a substantial percentage of the putative protein-coding open
      reading frames (ORFs) in viral genomes is unknown. As their sequence is not
      similar to that of proteins of known function, the function of these ORFs cannot
      be assigned on the basis of sequence similarity. Methods complement or in
      combination with sequence similarity-based approaches are being explored. The web
      based software SVMProt (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi) to some
      extent assigns protein functional family irrespective of sequence similarity and
      has been found to be useful for studying distantly related proteins [Cai, C.Z.,
      Han, L.Y., Ji, Z.L., Chen, X., Chen, Y.Z., 2003. SVM-Prot: web-based support
      vector machine software for functional classification of a protein from its
      primary sequence. Nucleic Acids Res. 31(13): 3692-3697]. Here 25 novel viral
      proteins are selected to test the capability of SVMProt for functional family
      assignment of viral proteins whose function cannot be confidently predicted on by
      sequence similarity methods at present. These proteins are without a sequence
      homolog in the Swissprot database, with its precise function provided in the
      literature, and not included in the training sets of SVMProt. The predicted
      functional classes of 72% of these proteins match the literature-described
      function, which is compared to the overall accuracy of 87% for SVMProt functional
      class assignment of 34582 proteins. This suggests that SVMProt to some extent is
      capable of functional class assignment irrespective of sequence similarity and it
      is potentially useful for facilitating functional study of novel viral proteins.

PMID- 15582661
TI  - The pseudorabies virus US3 protein kinase possesses anti-apoptotic activity that
      protects cells from apoptosis during infection and after treatment with sorbitol
      or staurosporine.
AB  - Most large DNA viruses, like herpesviruses, encode anti-apoptotic proteins to
      interfere with the apoptotic cellular response to infection. Previous studies
      have shown that the US3 protein kinase of herpes simplex virus, in contrast to
      US3 of bovine herpes virus 1, is very potent in protecting cells from apoptosis
      induced by the virus itself or by a broad range of exogenous apoptotic stimuli.
      Here, we demonstrate that US3 of the swine alphaherpesvirus pseudorabies virus
      (PRV) suppresses PRV-induced apoptosis in swine-testicle (ST) cells at late
      stages in infection, and that it protects ST cells from apoptosis induced by
      either sorbitol or staurosporine. Interestingly, PRV US3 encodes a short and a
      long isoform, the latter of which contains a functional mitochondrial
      localization sequence. Transient transfections showed that the PRV US3 long
      isoform is more efficient in protecting ST cells from PRV- or staurosporine
      induced apoptosis, suggesting a potential advantage for the mitochondrial
      localization of PRV US3 in implementing its anti-apoptotic function.

PMID- 15582662
TI  - Rescue of memory CD8+ T cell reactivity in peptide/TLR9 ligand immunization by
      codelivery of cytokines or CD40 ligation.
AB  - The capability of cellular immune components to rapidly recall upon challenge in
      most situations decides the efficacy of a vaccine. Here, we show that
      immunization of mice with SSIEFARL peptide (immunodominant epitope in
      glycoprotein B of herpes simplex virus type 1, aa498-505) combined with TLR9
      ligand in the absence of helper CD4(+) T cell activation generates a functionally
      impaired CD8(+) T cell memory response. Codelivery of IL-12, IL-15, or anti-CD40
      together with MHC class-I-restricted peptide combined with TLR9 ligand at
      inception of immunization resulted in generation of memory CD8(+) T cells that
      were several fold less compromised than immunization with peptide alone.
      Furthermore, administration of either plasmid DNA encoding IL-15 or anti-CD40 mAb
      but not rIL-12 during the memory phase restored the reactivity of memory CD8(+) T
      cells. Moreover, the rescued CD8(+) T cells preserved their cytotoxic capability
      and were able to clear a recombinant vaccinia virus encoding glycoprotein B of
      HSV. Our results indicate that good memory CD8(+) T cell response to peptide
      immunization can be achieved by using costimulatory procedures at the time of
      priming or recall immunization.

PMID- 15582663
TI  - Selective alterations of the host cell architecture upon infection with
      parvovirus minute virus of mice.
AB  - During a productive infection, the prototype strain of parvovirus minute virus of
      mice (MVMp) induces dramatic morphological alterations to the fibroblast host
      cell A9, resulting in cell lysis and progeny virus release. In order to
      understand the mechanisms underlying these changes, we characterized the fate of
      various cytoskeletal filaments and investigated the nuclear/cytoplasmic
      compartmentalization of infected cells. While most pronounced effects could be
      seen on micro- and intermediate filaments, manifest in dramatic rearrangements
      and degradation of filamentous (F-)actin and vimentin structures, only little
      impact could be seen on microtubules or the nuclear envelope during the entire
      monitored time of infection. To further analyze the disruption of the
      cytoskeletal structures, we investigated the viral impact on selective regulatory
      pathways. Thereby, we found a correlation between microtubule stability and MVM
      induced phosphorylation of alpha/beta tubulin. In contrast, disassembly of actin
      filaments late in infection could be traced back to the disregulation of two F
      actin associated proteins gelsolin and Wiscott-Aldrich Syndrome Protein (WASP).
      Thereby, an increase in the amount of gelsolin, an F-actin severing protein was
      observed during infection, accounting for the disruption of stress fibers upon
      infection. Concomitantly, the actin polymerization activity also diminished due
      to a loss of WASP, the activator protein of the actin polymerization machinery
      the Arp2/3 complex. No effects could be seen in amount and distribution of other
      F-actin regulatory factors such as cortactin, cofilin, and profilin. In summary,
      the selective attack of MVM towards distinct host cell cytoskeletal structures
      argues for a regulatory feature during infection, rather than a collapse of the
      host cell as a mere side effect of virus production.

PMID- 15582664
TI  - Characterization of the replication of a baculovirus mutant lacking the DNA
      polymerase gene.
AB  - In a previous study, the DNA polymerase gene (dnapol) of Autographa californica
      multiple nucleopolyhedrovirus (AcMNPV) was identified as one of six genes
      required for plasmid replication in a transient replication assay (M. Kool, C.
      Ahrens, R.W. Goldbach, G.F. Rohrmann, J.M. Vlak, Identification of genes involved
      in DNA replication of the Autographa californica, Proc. Natl. Acad. Sci. U.S.A.
      91, (1994) 11212-11216); however, another study based on a similar approach
      reported that the virally encoded polymerase was only stimulatory (A. Lu, L.K.
      Miller, The roles of 18 baculovirus late expression factor genes in transcription
      and DNA replication, J. Virol. 69, (1995) 975-982). To reconcile the conflicting
      data and determine if the AcMNPV DNA polymerase is required for viral DNA
      replication during the course of an infection, a dnapol-null virus was generated
      using bacmid technology. To detect viral DNA replication, a highly sensitive
      assay was designed based on real-time PCR and SYBR green chemistry. Our results
      indicate that a bacmid in which the dnapol ORF was deleted is unable to replicate
      its DNA when transfected into Spodoptera frugiperda (Sf-9) cells, although when
      the dnapol ORF was introduced into the polyhedrin (polh) locus, this repaired
      virus could propagate at levels similar to the control virus. These results
      confirm that the AcMNPV-encoded DNA polymerase is required for viral DNA
      replication and the host DNA polymerases cannot substitute for the viral enzyme
      in this process.

PMID- 15582665
TI  - HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine
      threonine kinases.
AB  - Mammalian genomes encode two related serine-threonine kinases, nuclear Dbf2
      related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae
      Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1
      retrotransposition. Since several virion-incorporated kinases regulate the
      infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that
      the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here
      we show that the NDR1 and NDR2 kinases were incorporated into HIV-1 particles.
      Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR), both within
      virions and within producer cells. Truncation at the PR cleavage site altered
      NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity.
      These studies identify two new virion-associated host cell enzymes and suggest a
      novel mechanism by which HIV-1 alters the intracellular environment of human
      cells.

PMID- 15582667
TI  - Self-injurious behaviour: a comparison of caffeine and pemoline models in rats.
AB  - Self-injurious behaviour (SIB) is a debilitating behaviour disorder that can have
      life-threatening consequences. It is often exhibited in intellectually
      handicapped and autistic populations, and it has been modeled with
      pharmacological manipulations in animals. We have characterized the induction of
      SIB using high doses of caffeine and pemoline in rats. Caffeine only produced
      very mild SIB in a small proportion of the rats, when administered repeatedly at
      very high doses (140-185 mg/kg/day). All the caffeine-treated rats showed
      profound signs of caffeine-toxicity at these doses, and lower doses did not
      induce any self-injury. On the other hand, pemoline was effective across a range
      of doses (100-300 mg/kg/day), including doses that did not produce overt signs of
      toxicity (100-200 mg/kg/day). The topography of the tissue injury sites (tail vs.
      paws and ventrum) differed between caffeine and pemoline treatments, and across
      doses of pemoline. The speed of onset, the incidence, and the severity of SIB
      occurred in a dose-orderly manner across the pemoline doses, and there was
      substantial individual variability in the induction of SIB when a moderately high
      dose (200 mg/kg/day) was used. These individual differences in vulnerability to
      self-injure are reminiscent of the fact that some humans with specific
      neurobiological disorders express SIB and some individuals with those same
      disorders do not. Accordingly, the pemoline model of SIB may be useful to
      investigate the neurobiological basis of factors that contribute to etiology of
      SIB.

PMID- 15582666
TI  - Proteins of the PIAS family enhance the sumoylation of the papillomavirus E1
      protein.
AB  - Sumoylation of the papillomavirus (PV) origin binding helicase E1 protein is
      critical for its function. Consequently, factors modulating the sumoylation of E1
      could ultimately alter the outcome of a papillomavirus infection. We investigated
      the role played by phosphorylation and two known SUMO E3 ligases, RanBP2 and PIAS
      proteins, on the sumoylation of E1. E1 sumoylation was unaffected by
      phosphorylation as both wild-type and pseudo-phosphorylation mutants of BPV E1
      exhibited similar sumoylation profiles. RanBP2 bound to BPV E1, but not to HPV11
      E1, and lacked sumoylation enhancing activity for either E1. In contrast,
      proteins of the PIAS family (except PIASy) bound to both BPV and HPV11 E1 and
      stimulated their sumoylation. The structural integrity of the RING finger domain
      of the PIAS proteins was required for their E3 SUMO ligase activity on PV E1
      sumoylation but was dispensable for their PV E1 binding activity. Miz1, the PIAS
      protein exerting the strongest E1 sumoylation enhancing activity, favored SUMO1
      versus SUMO2 as the modifier and was shown to be transcribed in a keratinocyte
      cell line. This study indicates PIAS proteins as possible modulators of PV E1
      sumoylation during papillomavirus infections.

PMID- 15582668
TI  - In alcohol-treated rats, naloxone decreases extracellular dopamine and increases
      acetylcholine in the nucleus accumbens: evidence of opioid withdrawal.
AB  - Withdrawal from ethanol is aversive. The question is why. As with the withdrawal
      from morphine, nicotine, diazepam and sugar, the ethanol withdrawal state may
      involve an increase in nucleus accumbens (NAc) acetylcholine (ACh) causing an
      alteration of the dopamine (DA)-ACh balance in favor of ACh. Therefore the
      effects of acute and chronic alcohol (1 gm/kg/day i.p.) treatment on
      extracellular concentrations of NAc ACh and DA were determined before and after
      naloxone-precipitated withdrawal. Ethanol initially increased DA to 119% of
      baseline as measured by microdialysis. This was still the case on the 21st day of
      ethanol injection when DA increased to 126%. There was no effect of ethanol on
      ACh. However, naloxone (3 mg/kg s.c.) injected the next day decreased
      extracellular DA to 83% of baseline and caused a significant rise in ACh to 119%.
      This state of high ACh combined with low DA may contribute to the aversive
      aspects of alcohol withdrawal.

PMID- 15582669
TI  - Chronic lithium decreases Nurr1 expression in the rat brain and impairs spatial
      discrimination.
AB  - Lithium (Li+) is a drug used for the treatment of neuropsychiatric disorders,
      whereas Nuclear receptor-related factor 1 (Nurr1) has been implicated in normal
      and aberrant cognitive processes. Li+'s effects on cognition and Nurr1 expression
      were examined. Rats were exposed to Li+ in their diet for 4 weeks and only those
      reaching Li+ blood concentrations within the established clinically therapeutic
      range were used. Li+ decreased rearing activity in rats, but did not affect
      horizontal locomotion nor object recognition memory. In contrast, Li+ treated
      animals were significantly impaired in the initial, but not late, stages of
      acquisition of a hippocampal-dependent spatial discrimination task. In agreement
      with the behavioral results, chronic Li+ caused a significant downregulation of
      basal Nurr1 expression in several brain regions. In particular, a significant
      negative correlation between Li+ blood levels and Nurr1 expression was identified
      in the CA1 hippocampal subregion, but not in CA3, perirhinal cortex or the dorsal
      endopiriform nucleus. Upregulation of hippocampal Nurr1 levels to those of
      controls were observed in Li+ treated rats following training in the spatial
      task. Overall, the results suggest that the effects of Li+ on the brain may be
      particularly relevant to hippocampal-dependent cognitive processes involving
      Nurr1 expression.

PMID- 15582670
TI  - Ethanol preexposure increases ethanol self-administration in C57BL/6J and DBA/2J
      mice.
AB  - Genetic variables are thought to interact with environmental factors, such as
      alcohol exposure history, to produce individual differences in alcohol abuse and
      alcoholism. The objective of this study was to test the potential interaction
      between genetic predisposition to consume alcohol and alcohol pretreatment on
      subsequent self-administration. To accomplish this goal, four groups of mice from
      the ethanol-avoiding DBA/2J (D2) and ethanol-preferring C57BL/6J (B6) inbred
      strains were exposed to saline, acute ethanol (2 g/kg), or chronic intermittent
      ethanol (1 or 2 g/kg) intraperitoneal (i.p.) injections. Locomotor activity was
      monitored after each injection. After preexposure, animals were given a two
      bottle choice test with various concentrations of ethanol/sucrose vs. sucrose or
      ethanol vs. water for 4 days at each concentration. Then, all animals were
      challenged with a 2.0 g/kg ethanol i.p. injection and locomotor activity was
      assessed. Acute and chronic ethanol pretreatment increased locomotor activity in
      response to a challenge dose of ethanol (2 g/kg) in D2 mice but had no effect on
      B6 mice. Prior exposure to ethanol altered the amount of ethanol consumed in a
      mouse strain-dependent manner. D2 mice showed a positive relationship between
      ethanol intake and dose or duration of ethanol preexposure. B6 mice preexposed to
      ethanol consumed more ethanol than naive animals, independent of dose or duration
      of exposure. During the last phase of self-administration testing, D2 mice
      exposed to chronic ethanol (2 g/kg) consumed as much ethanol as B6 from the same
      pretreatment condition. After a history of ethanol self-administration, saline
      control mice from the D2 strain showed equal locomotor activation as compared to
      D2 mice that were pretreated with ethanol injections. B6 mice showed no change in
      locomotor activity after ethanol self-administration or injection. These results
      demonstrate that genetic predisposition to avoid alcohol (D2 mice) can be
      modified by a history of preexposure and that a predisposition to prefer alcohol
      (B6 mice) may be also amenable to influence by drug history. In general, the
      results of this study suggest that genetic factors may interact with previous
      exposure to ethanol to modify ethanol self-administration.

PMID- 15582671
TI  - Fear conditioning is associated with altered integration of PLC and ERK signaling
      in the hippocampus.
AB  - The extracellular signal-regulated protein kinases (ERKs) are proline-directed,
      serine/threonine kinases that regulate a variety of cellular functions, including
      proliferation, differentiation, and plasticity. In the present report, we provide
      evidence that ERK2 and phosphatidylinositol-specific phospholipase C (PLC)-beta
      and -gamma isozymes interact in the rat hippocampal formation. We found that anti
      PLC-beta1a, -beta2, -beta4, -gamma1 and -gamma2, but not -beta3, immune complexes
      isolated from rat hippocampal formation postnuclear fractions contain anti-ERK2
      immunoreactivity. Further, we show that PLC catalytic activity is associated with
      anti-ERK2 immunoprecipitates isolated from the hippocampal formation, and that
      the amount of enzyme activity is significantly increased following fear
      conditioned learning. The observed interactions may be mediated by consensus
      sequences conforming to an ERK2 docking site, termed a D-domain, that we
      identified in PLC-beta1a, -beta2, -beta4 -gamma1 and -gamma2. Based on these
      results, we propose that PLC-beta and PLC-gamma isozymes form signaling complexes
      with ERK2 in rat brain, and these complexes play critical roles in learning and
      memory, as well as a variety of other neuronal functions.

PMID- 15582672
TI  - Behavioral reactivity to a noradrenergic challenge after chronic oral
      methylphenidate (ritalin) in rats.
AB  - Methylphenidate (Ritalin) is routinely used for the treatment of attention
      deficit/hyperactivity disorder (ADHD). It is a psychomotor stimulant with
      pharmacodynamics similar to those established for cocaine and amphetamine with
      primary activation of the noradrenergic and dopaminergic systems. Long-term
      exposure to psychostimulants including methylphenidate (MPD) is believed to
      result in enduring functional changes along both these pathways and various
      behaviors mediated by these systems may be affected. In the present experiment,
      the effects of intermittent oral administration of methylphenidate (10 mg/kg) to
      rats over a 4-week period were subsequently (after a drug washout interval)
      assessed in three animal models sensitive to noradrenergic manipulation: the
      elevated plus-maze, predator odor avoidance, and social interaction tests. The
      behaviors of methylphenidate-experienced animals were compared with untreated
      controls. Thirty minutes prior to testing, half the animals with each of these
      histories received an injection of yohimbine hydrochloride (2.0 mg/kg), an alpha2
      adrenoreceptor blocker intended to evoke noradrenergic system activation, while
      the remainder received a saline injection. Yohimbine was expected to reduce both
      exploration of novel stimuli and interaction with conspecifics, and it was
      predicted that methylphenidate would potentiate these effects. Relative to saline
      tested controls, rats that received both the methylphenidate treatment and the
      yohimbine challenge exhibited the least exploration in the predator odor test and
      the lowest duration of interaction with an unfamiliar conspecific partner in the
      social interaction test. The behavior patterns observed in this group of rats
      suggest heightened emotionality and defensiveness that are typically seen when
      rats are administered drugs known to be anxiogenic in human subjects. In the plus
      maze, exploratory locomotor activities remained unaltered by either drug while
      yohimbine decreased risk-assessment behaviors, an effect that remained
      uninfluenced by methylphenidate pretreatment.

PMID- 15582673
TI  - Protective effect of chronic ethyl docosahexaenoate administration on brain
      injury in ischemic gerbils.
AB  - There is evidence that the excessive generation of reactive oxygen free radicals
      contributes to the brain injury associated with cerebral ischemia. In the present
      study, the protective effect of chronic administration of ethyl docosahexaenoate
      (E-DHA) against oxidative brain injury was evaluated in the gerbil model of
      transient cerebral ischemia. Weanling male gerbils were orally pretreated with
      either E-DHA (200 mg/kg) or vehicle, once a day, for 10 weeks and subjected to
      bilateral occlusion of common carotid arteries for 10 min. At the different
      reperfusion times, E-DHA pretreatment significantly inhibited the increases in
      the production of brain salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA)
      and content of brain malonildialdehyde (MDA). The superoxide dismutase (SOD)
      activity was not modified; however, pretreatment with E-DHA significantly
      prevented the level of brain-reduced glutathione (GSH) and activities of brain
      glutathione peroxidase (GSH-P(X)) and catalase (CAT) from declines caused by
      cerebral ischemia. Moreover, ischemia and reperfusion-induced delayed neuronal
      loss in the hippocampus CA1 sector and locomotor hyperactivity were also
      significantly attenuated by pretreatment with E-DHA. These results suggested that
      the neuroprotective effect of E-DHA might be due to its antioxidant property.

PMID- 15582674
TI  - Continuous administration of opioids produces locomotor sensitization.
AB  - Sensitization, a behavioral phenomenon characterized by an escalating pattern of
      drug response following repeated administration, is thought to be involved in the
      development of addiction. Research on certain drugs of abuse, most notably the
      psychomotor stimulants amphetamine and cocaine, suggests that two factors are
      important to the development of sensitization: (1) drugs must be administered
      intermittently, rather than continuously, and (2) drugs must be administered in
      association with specific environmental cues. The present studies were performed
      to determine if the same requirements exist for opioid sensitization. If
      sensitization occurs following continuous infusion of the drugs, then neither
      intermittent administration nor specific environmental cues can be critical.
      Morphine was administered continuously with pellets (2 x 75 mg) or osmotic pumps
      (20 mg/kg/day), and fentanyl was administered continuously with osmotic pumps
      (0.2 mg/kg/day) to male Sprague-Dawley rats. Continuous infusion of either
      morphine or fentanyl led to an escalating pattern of activity that is
      characteristic of sensitization to the locomotor effects of the drugs. The
      escalation of activity was evident across different measures of activity, and
      persisted beyond continuous administration. The results suggest that, unlike
      sensitization to cocaine or amphetamine, intermittent administration and
      environmental specificity are not critical to opioid sensitization. These
      findings may have implications for the treatment of pain and addiction.

PMID- 15582675
TI  - Allostasis and dysregulation of corticotropin-releasing factor and neuropeptide Y
      systems: implications for the development of alcoholism.
AB  - Alcoholism is a chronic relapsing disorder, accompanied by alterations in
      psychological and physiological functioning, which reaches an addictive state
      where an individual demonstrates uncontrollable compulsive alcohol drinking and
      impairment in social and occupational functioning. Withdrawal is one of the
      defining characteristics of dependence, characterized by impaired physiological
      function and enhanced negative affect, and is thought to be a major contributing
      factor to relapse. The negative emotional aspects of withdrawal appear to be more
      involved in continued alcohol craving because physical withdrawal symptoms are
      not highly correlated with relapse in alcoholics. Allostasis describes
      maintaining stability outside the homeostatic range by varying the internal
      milieu to match environmental demands. This concept has been applied to
      neurobiological models of drug addiction and is thought to contribute to the
      vulnerability of drug addicts to relapse, as addicts continue to use drugs in
      order to maintain their psychological state within a homeostatic range. With
      regard to alcohol, two neuropeptides appear to be involved in the regulation of
      alcohol-related stress, corticotropin-releasing factor (CRF), which is associated
      with an increased stress response and negative affect, and neuropeptide Y (NPY),
      a neuropeptide with anxiolytic properties. The hypothesis to be developed in the
      present review is that a dysregulation of the CRF and NPY systems significantly
      contributes to the motivational basis of continued alcohol-seeking behavior
      during alcohol dependence. It appears that increases in CRF contribute to the
      negative affective state that is strongly associated with alcohol withdrawal, and
      NPY provides a motivational basis to consume alcohol because the anxiolytic
      effects of alcohol, which are strongly associated with relapse, appear to be
      regulated in part by this neuropeptide.

PMID- 15582676
TI  - Phosphodiesterase inhibition by sildenafil citrate attenuates the learning
      impairment induced by blockade of cholinergic muscarinic receptors in rats.
AB  - We examined whether treatment with sildenafil citrate (the active compound of
      Viagra), a cyclic nucleotide phosphodiesterase type 5 inhibitor (PDE5), would
      reverse the learning impairment induced by cholinergic muscarinic (mACh) receptor
      blockade [0.75 mg/kg scopolamine HCl, intraperitoneal (i.p.) injections]. Rats
      were pretrained in a one-way active avoidance of foot shock in a straight runway
      and the next day received 15 training trials in a 14-unit T-maze. Performance in
      this maze paradigm requires accurate responding to avoid mild foot shock and has
      been shown to be sensitive to aging and to impairment in central cholinergic
      systems. Intraperitoneal (i.p.) injections of scopolamine or saline and
      sildenafil or vehicle were given 30 and 15 min before training, respectively. The
      combined treatment conditions were as follows: saline+vehicle (control),
      scopolamine (0.75 mg/kg)+vehicle, and scopolamine (0.75 mg/kg)+sildenafil (1.5,
      3.0, or 4.5 mg/kg). Behavioral measures of performance included deviations from
      the correct pathway (errors), run time from start to goal, shock frequency, and
      duration. Statistical analysis revealed that scopolamine impaired maze
      performance and that sildenafil (3.0 mg/kg) significantly attenuated this
      impairment in a dose-dependent manner. These results suggest that sildenafil
      citrate may serve as a cognitive enhancer for therapeutic treatment of
      cholinergic dysfunction in age-related cognitive decline and Alzheimer's dementia
      (AD).

PMID- 15582677
TI  - Adolescent gamma-hydroxybutyric acid exposure decreases cortical N-methyl-D
      aspartate receptor and impairs spatial learning.
AB  - gamma-hydroxybutyric acid (GHB), which belongs to the class of substances
      referred to as "club drugs", is abused for its euphoric, sedative and anabolic
      effects. GHB use and abuse is most prevalent among adolescents and young adults.
      In almost all cases of GHB abuse, subjects report of amnesia. Behavioral effects
      of GHB in animals, particularly on learning and memory are not known. In this
      study, effects of GHB exposure on spatial learning and memory in adolescent rats
      were tested using the Morris water maze (MWM). Adolescent male rats were treated
      with a single daily injection of one of three doses of GHB for 5 days; control
      rats received equivalent volumes of saline. GHB-treated rats took longer and swam
      greater distances to find the hidden platform than control rats. Swim speed in
      GHB-treated rats was no different from that in vehicle-treated rats. In the probe
      trial, adolescent rats exposed to GHB spent less time in the target quadrant than
      control rats. In the visual task, drug-treated rats did not perform any
      differently than control rats. Brain regions from GHB-exposed and saline-treated
      rats were examined for N-methyl-D-aspartate (NMDA) receptor changes using [3H]MK
      801 binding as a biochemical marker for NMDA channel function. [3H]MK-801 binding
      in the frontal cortex was significantly reduced compared to saline-treated
      controls. Together, these data indicate that GHB exposure in adolescent rats
      negatively impacts spatial learning and this is associated with altered
      regulation of cortical NMDA receptor.

PMID- 15582678
TI  - Thirst changes in offspring of hyperreninemic rat dams.
AB  - The aim of this study was to investigate the changes in thirst dependence on the
      renin-angiotensin system (RAS), in offspring of hyperreninemic, hyperdipsic, and
      natriophilic rat dams. Female rats underwent a partial aortic ligature between
      the renal arteries (PAL) or were sham-operated (SHAM). At 6 days of age,
      offspring of PAL (O-PAL) and SHAM (O-SHAM) dams were injected with isoproterenol
      (subcutaneously, 500 microg/kg body weight) or vehicle. Pretreatment with
      captopril (intraperitoneally, 50 mg/kg) on isoproterenol-induced thirst was also
      studied. Plasma renin activity in dams and hematocrit and osmolality in pups were
      measured. O-PAL had a greater water intake than O-SHAM. However, they responded
      similarly to isoproterenol or isoproterenol with captopril pretreatment. Only
      minor differences in hematocrit and osmolality were found between O-SHAM and O
      PAL rats after isoproterenol or vehicle treatment. Beta-adrenergic or
      angiotensinergic responsivity seems not to be altered in offspring of
      hyperrenimic, hyperdipsic, and natriophilic dams. Nevertheless, other thirst
      responses of offspring may be critically dependent upon uterine conditions.

PMID- 15582679
TI  - Scopolamine during the paradoxical sleep window impairs radial arm maze learning
      in rats.
AB  - It has been proposed that there are paradoxical sleep windows (PSW) during which
      REM sleep is required for effective learning. Thus, rats deprived of REM sleep
      during 0-4 (but not 5-8) h after training show impaired learning of a radial maze
      task. As cholinergic (ACh) systems are active during REM sleep and may be
      involved in learning, this experiment investigated the effects on learning of
      pharmacological manipulation of the cholinergic system during the period
      identified as the PSW. Sprague-Dawley rats were randomly assigned to groups that
      were physically deprived of REM for 4 h either immediately after training or
      beginning 4 h after training or treated with the ACh receptor antagonist
      scopolamine (0-0.4 mg/kg at 0 and 2 h after training or 0.006 mg/kg at 4 and 6 h
      after training) on each of 9 days of radial maze training. Post-training REM
      deprivation (0-4 h but not 5-8 h after training) and scopolamine dose-dependently
      impaired learning. Results suggest that REM sleep and intact ACh
      neurotransmission are required during the PSW for rats to learn the radial maze
      task.

PMID- 15582680
TI  - Memory deficit and reduced anxiety in young adult rats given repeated
      intermittent MDMA treatment during the periadolescent period.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational
      drug among adolescents that is often taken primarily on weekends. The goals of
      this study were to develop a model of the typical intermittent pattern of human
      MDMA use in periadolescent rats and to determine the behavioral consequences of
      MDMA exposure in this model. Male Sprague-Dawley rats received s.c. injections of
      10 mg/kg of MDMA or saline twice daily with an interdose interval of 4 h.
      Treatments were given every fifth day from postnatal day (PD) 35 to PD 60.
      Beginning at PD 65, the animals were tested for open-field activity, object
      recognition memory, and anxiety-related behaviors in the elevated plus-maze.
      Brain tissues were collected at PD 70 for determination of radiolabeled
      paroxetine binding to the serotonin transporter (SERT) in the neocortex and
      hippocampus. Repeated MDMA administration led to a reduced rate of weight gain
      that was evident by PD 50. There was no treatment effect on ambulatory behavior
      in the open-field. However, the MDMA group displayed an impairment of object
      recognition memory and reduced anxiety as indicated by a twofold increase in open
      arm duration in the elevated plus-maze. Only modest decreases in SERT binding
      were observed, although there was a significant negative correlation between
      hippocampal SERT levels and open-arm duration within the MDMA group. These
      findings demonstrate that intermittent MDMA exposure during the adolescent period
      of development can influence subsequent cognitive and affective functioning in
      the absence of severe serotonergic damage.

PMID- 15582681
TI  - Melatonin inhibits the development of tolerance to U-50,488H analgesia via
      benzodiazepine-GABAAergic mechanisms.
AB  - Melatonin, a primary secretory product of pineal gland, is known to produce many
      of its pharmacological actions via benzodiazepine-gamma-aminobutyric acidA
      (GABAA)ergic mechanisms. Recently, we showed that benzodiazepine-GABAAergic
      mechanisms play an important role in U-50,488H (U50) analgesia and its tolerance.
      Hence, in the present study, the effect of melatonin on U50 analgesia and its
      tolerance was investigated. Furthermore, the possible role of benzodiazepine
      GABAAergic mechanisms in the actions of melatonin on U50 analgesia was
      investigated. All experiments were performed using the radiant tail-flick test
      for mice. Melatonin [0.2, 1 and 5 mg/kg, intraperitoneal (i.p.)] neither produced
      analgesia nor affected the acute U50 (40 mg/kg, i.p.) analgesia. Tolerance to U50
      analgesia was induced by administering U50 (40 mg/kg, i.p.) twice daily over 6
      days. Treatment with melatonin (1 and 5 mg/kg, i.p) 15 min prior to each dose of
      U50 inhibited the development of tolerance, whereas a low dose of melatonin (0.2
      mg/kg, i.p.) did not. The inhibition of U50 tolerance by melatonin was reversed
      by the chronic treatment with flumazenil (0.1 mg/kg), a benzodiazepine receptor
      antagonist and picrotoxin (1 mg/kg), a GABAA-gated chloride channel blocker.
      Flumazenil and picrotoxin neither affected tail-flick latencies nor altered acute
      U50 analgesia and its tolerance. Interestingly, chronic 6-day melatonin treatment
      in a vehicle (U50-naive) group did not alter U50 analgesia measured on day 7.
      Together, these findings suggest that melatonin interferes with the neural
      mechanisms involved in the development of tolerance to U50 analgesia. The
      inhibition of U50 tolerance by melatonin was reversed by flumazenil and
      picrotoxin treatment, suggesting that benzodiazepine-GABAAergic mechanisms play
      an important role in the development of tolerance to U50 analgesia and that
      melatonin inhibits the development of U50 tolerance via benzodiazepine-GABAAergic
      mechanisms.

PMID- 15582682
TI  - Handling blocks expression of conditioned place aversion but not conditioned
      place preference produced by ethanol in mice.
AB  - Previous findings implicate opioid receptors in the expression of the conditioned
      rewarding and aversive properties of ethanol. We have recently reported that the
      conditioned rewarding effect of ethanol is mediated by opioid receptors in the
      ventral tegmental area (VTA). We attempted to determine whether VTA opioid
      receptors also mediate the expression of the conditioned aversive properties of
      ethanol. However, the magnitude of conditioned place aversion (CPA) was not
      consistent with our previous findings and prevented us from making definitive
      conclusions. We hypothesized that the handling required to make intracranial
      infusions in mice alters the expression of CPA, but not conditioned place
      preference (CPP). Therefore, non-operated animals underwent a Pavlovian
      conditioning procedure for either ethanol CPA or CPP. Just before testing, half
      of the animals were held by the scruff of the neck to mimic intracranial infusion
      handling. Animals conditioned for CPA did not express CPA if they were handled.
      However, animals conditioned for CPP exhibited robust CPP, regardless of
      handling. These findings provide additional evidence that the conditioned
      rewarding and aversive effects of ethanol are mediated by different neural
      mechanisms.

PMID- 15582683
TI  - Antiparkinsonian-like effects of Plumbago scandens on tremorine-induced tremors
      methodology.
AB  - Tremorine-induced tremors model is used to evaluate antiparkinsonian drugs
      because rest tremor is a sign that distinguishes Parkinson's disease (PD) from
      other diseases. The effects of crude ethanolic extract (CEE) and total acetate
      fraction (TAF) of Plumbago scandens were investigated at several doses. These
      extracts at doses of 125 and 250 mg/kg i.p. failed to reduce tremors in tremorine
      treated mice. TAF showed significant effects only at a dose of 500 mg/kg. Both
      CEE and TAF at doses of 1000 and 2000 mg/kg i.p. suppressed the tremors in a dose
      dependent fashion for 60 min. Biperiden, an anticholinergic drug, was used as
      standard at a dose of 3 mg/kg i.p. This study suggests that P. scandens is a
      plant with possible therapeutic value for PD.

PMID- 15582684
TI  - (+)-Methamphetamine-induced spontaneous behavior in rats depends on route of
      (+)METH administration.
AB  - These studies examined the role of (+)-methamphetamine ((+)METH) administration
      route on spontaneous behavioral activity vs. time relationships, and
      pharmacokinetic mechanisms for differences in effects. Male Sprague-Dawley rats
      (n=6 per administration route) received saline and three doses (0.3, 1.0 and 3.0
      mg/kg) of (+)METH in a mixed-sequence design by intravenous (iv), subcutaneous
      (sc) or intraperitoneal (ip) administration. Locomotion and stereotypy were
      quantified by video-tracking analysis. The effects of (+)METH on spontaneous
      behavior were dose- and route-dependent. In particular, total locomotor activity
      was greatest following 3.0 mg/kg intraperitoneally (P<0.05) and stereotypy
      ratings were greatest following 3.0 mg/kg subcutaneously (P<0.05). In addition,
      the duration of locomotor effects was greatest after 3.0 mg/kg subcutaneously
      (P<0.05). Serum pharmacokinetic parameters were determined in separate rats given
      3.0 mg/kg by subcutaneous and intraperitoneal administration (n=4 per
      administration route). The (+)METH elimination half-life was not different
      between the routes, but the (+)METH AUC was greater (P<0.05), and the (+)METH and
      (+)-amphetamine (AMP) maximum concentrations occurred later following
      subcutaneous than after intraperitoneal dosing (P<0.05), increasing and
      prolonging drug exposure. In conclusion, the overall pattern of (+)METH effects
      on locomotor activity depend on dose and the route of administration, which
      affects serum concentration and the time course of behavioral effects.

PMID- 15582685
TI  - Evidence for bidirectional cues as a function of time following treatment with
      amphetamine: implications for understanding tolerance and withdrawal.
AB  - RATIONALE: Previous drug-discrimination studies have focused on characterizing
      the cue properties associated with amphetamine's (AMPH) primary effect. Results
      from recent experiments indicate that equally prominent cues are associated with
      AMPH withdrawal. OBJECTIVES: The purpose of the present study was to investigate
      the extent to which AMPH-induced withdrawal cues, opposite to those associated
      with AMPH's primary effect are observed. METHODS: Since dopamine (DA) has been
      implicated in mediating the AMPH cue, rats were trained to discriminate between
      0.25 mg/kg AMPH, an indirect DA agonist, and 0.033 mg/kg haloperidol (HAL), a DA
      antagonist at the D2 receptor site. Training doses were chosen so that rats
      responded about equally on both levers when tested on saline (SAL) providing a
      behavioral baseline sensitive to assessing AMPH-related bidirectional changes in
      cue state. Following acquisition of the discrimination, rats were tested for
      choice of responding on the AMPH and HAL levers at intervals from 6 to 72 h
      following treatment with a single dose of 3.0 mg/AMPH. Also, in order to
      investigate the relationship between withdrawal and tolerance to AMPH's cue
      properties, AMPH dose-response curves were determined 24 h following treatment
      with SAL, 1.5 and 3.0 mg/kg AMPH. RESULTS: At short intervals after treatment
      with 3.0 mg/kg AMPH, rats responded primarily on the AMPH lever followed by a
      shift to predominant responding on the HAL lever 16-30 h post-treatment, before
      returning to predrug levels. Treatment with 1.5 and 3.0 mg/kg AMPH produced
      parallel dose-response curve shifts to the right. CONCLUSIONS: Following a single
      dose of AMPH, robust cues associated with AMPH withdrawal were observed that
      lasted approximately three times longer than the cues associated with the drug's
      primary effects. Furthermore, results from the tolerance tests indicate that
      tolerance reflects a baseline shift rather than a loss in drug efficacy.

PMID- 15582686
TI  - The effect of recombinant swine interleukin-4 on swine immune cells and on pro
      inflammatory cytokine productions in pigs.
AB  - The in vitro effect and the in vivo influence of recombinant swine IL-4 (rSwIL-4)
      were characterized in various swine cells and in nursery pigs on LPS-induced
      endotoxic shock and pro-inflammatory cytokine productions. In in vitro
      experiment, the rSwIL-4 induced a proliferation of CD4 positive T cells in
      mitogen-prestimulated peripheral blood mononuclear cell (PBMC). In addition, the
      rSwIL-4, which was produced from insect cells, promoted the differentiation of
      monocytes into immature dendritic cells in combination with granulocyte
      macrophage-colony stimulating factor (GM-CSF). Furthermore, the rSwIL-4
      successfully suppressed the LPS-induced secretion of TNF-alpha, IL-1alpha, IL-6,
      IL-8, and IL-18 from swine alveolar macrophages when rSwIL-4 was treated at the
      same time with LPS. In in vivo experiment in nursery pigs, subcutaneous
      pretreatment of rSwIL-4, which was produced from baculovirus expression system,
      enhanced the severity of respiratory failure with endotoxic shock, and increased
      the production of TNF-alpha and IL-18 in response to inoculation with LPS. These
      results indicate that the rSwIL-4 is biologically active in both in vitro and in
      vivo treatments. Depending on the administration time, pro-inflammatory cytokine
      productions by IL-4 can cause either inhibitory or stimulatory regulation.

PMID- 15582687
TI  - Expression and characterization of the recombinant swine interleukin-6.
AB  - The swine interleukin-6 (SwIL-6) cDNA was cloned by RT-PCR and each expression
      system of recombinant SwIL-6 in Escherichia coli, insect cells, and mammalian
      cells was developed. Recombinant SwIL-6 produced in bacteria was applied for
      generation of the polyclonal antibodies. The rSwIL-6 was purified from
      supernatant of insect cells with a Q-sepharose or anti-SwIL-6 monoclonal antibody
      based immunoaffinity column. The antibodies showed that the molecular weight of
      rSwIL-6 was approximately 26kDa in E. coli, 25, 26, 30kDa in insect cells, and 26
      and 30kDa in mammalian cells. These variations of molecular weight were probably
      due to the different modifications of glycosylation. All these recombinant
      proteins retained the antigenicity and biological activity on 7TD1 mouse cells.

PMID- 15582688
TI  - Establishment of swine interleukin-6 sandwich ELISA.
AB  - We established a sandwich enzyme-linked immunosorbent assay (ELISA) for swine
      interleukin-6 (SwIL-6), which was applied for detection of SwIL-6 in vitro and in
      vivo. Anti-SwIL-6 rabbit- and goat-polyclonal antibodies, and monoclonal antibody
      (mAb) were prepared, conforming that all of the antibodies were reactive with
      recombinant SwIL-6 by Western blotting and indirect ELISA. A sandwich ELISA was
      developed using the mAb as a capture antibody and biotinylated goat-polyclonal
      antibody as a detection antibody. The detection limit of the sandwich ELISA for
      rSwIL-6 was 49pg/ml and did not show cross-reactivity with swine IL-1b, IL-4, IL
      8, IL-18, IL-12, and IFN-g. Using the ELISA, SwIL-6 was detected in culture
      medium of the monocytes stimulated with PHA-P and PMA, and the plasma or the
      bronchoalveolar lavage fluid (BALF) of pigs experimentally infected with
      Actinobacillus pleuropneumoniae or Mycoplasma hyopneumoniae. This ELISA for SwIL
      6 may be useful for understanding the role of this cytokine in various swine
      diseases.

PMID- 15582689
TI  - Molecular detection of Yersinia pestis isolates of Indian origin by using Pla
      specific monoclonal antibodies.
AB  - Monoclonal antibodies (MAbs) were generated against the recombinant plasminogen
      activator (Pla) protein of Yersinia pestis. These MAbs detected Pla in all the 18
      isolates of Y. pestis obtained from the sputum of pneumonic plague patients and
      from the liver and spleen of rodents from plague-affected areas of India during
      1994-1995 as well as in seven of the eight isolates obtained from rodents in the
      surveillance regions of Hosur and Palmner in India during 1998 by simple dot
      ELISA. In immunoblotting, the MAbs reacted with the Pla antigen only in Y. pestis
      isolates at 37 and 35kDa region. These monoclonal antibodies, being strictly
      specific, can be used for detecting Y. pestis isolates that are Fraction 1
      antigen-negative. Also, the radiolabelled pla fragment hybridized specifically to
      the representative DNA samples of Y. pestis isolates.

PMID- 15582690
TI  - Nonspecific immune response of peripheral blood neutrophils in two horse breeds
      (Anglo-Arabian and Spanish-Arabian): response to exercise.
AB  - The aim of the present paper was: (1) to find out if there were any differences
      in the nonspecific immunological pattern of peripheral blood neutrophil between
      two breeds of horses (AA and SA); (2) to evaluate the effects of an exercise in
      the aerobic-anaerobic threshold. This has been observed in a group of 11
      untrained horses (6 SA and 5 AA) of 2.5 years old. No statistically significant
      differences were found in the different stages of immune response between the
      rest and immediately after physical exercise to two breeds. However, the
      chemotaxis was significant higher at rest in the AA than SA breed. A positive
      correlation was found at rest between the phagocytic and oxidative metabolism
      activity for AA breed and a negative correlation too between the adherence and
      chemotaxis with phagocytic capacity, immediately after exercise test, for the
      same breed.

PMID- 15582691
TI  - A combined bovine herpesvirus 1 gB-gD DNA vaccine induces immune response in
      mice.
AB  - Although DNA vaccines have several advantages over conventional vaccines,
      antibody production and protection are often not adequate, particularly in single
      plasmid vaccine formulations. Here we assessed the potential for a combined
      vaccine based on plasmids encoding the membrane-anchored or secreted forms of
      bovine herpesvirus type 1 (BHV-1) glycoprotein B and D (gB and gD) to induce
      neutralizing and cell mediated immune responses in mice. Animals were injected by
      intramuscular, subcutaneous and intranasal routes. Mice immunized with the
      combined vaccine containing the secreted forms of BHV-1 glycoproteins developed
      higher titers of anti-BHV-1 neutralizing antibodies, compared to wild type gB/gD
      combined plasmids and to single plasmid injected groups. Cellular immunity was
      also developed in mice immunized with combined vaccines, whereas low or no
      response were observed in single plasmid injected animals. The data suggest the
      potential use of this combined vaccine in in vivo trials of calves, in order to
      evaluate its protective efficacy.

PMID- 15582692
TI  - Real-time RT-PCR for norovirus screening in shellfish.
AB  - Real-time RT-PCR, combining amplification and detection of virus-specific
      amplicons, is a promising tool for norovirus detection in environmental or food
      samples such as shellfish. We developed a real-time RT-PCR assay based on one
      step detection using single primer sets and probes for norovirus genogroups I and
      II. Seventy and seven RT-PCR units of genogroup I and II reference norovirus
      strains, respectively, were detected in artificially contaminated oysters.
      Validation of the new method on 150 archived naturally contaminated shellfish
      confirmed the utility of the genogroup II primer set to detect a large range of
      different strains circulating in France since 1995, but genogroup I strains were
      detected infrequently.

PMID- 15582693
TI  - Identification of a monoclonal antibody from Peromyscus maniculatus (deer mouse)
      cytomegalovirus (PCMV) which binds to a protein with homology to the human CMV
      matrix protein HCMV pp71.
AB  - In this study we identified and characterized a monoclonal antibody against the
      matrix protein of a cytomegalovirus isolated from the common deer mouse
      (Peromyscus maniculatus) (PCMV). The monoclonal antibody was isolated using
      previously described technology which could be applied to the production of
      monoclonal antibodies against zoonotic disease. The antibody was found to react
      with a protein homologous to the human cytomegalovirus (HCMV) matrix protein
      (pp71), the product of the UL82 open reading frame (ORF). mAbs were generated
      from heterologous fusion of spleen cells from PCMV-positive mice and Balb/C P3X63
      Ag8.653 myeloma cells. Using this approach, four monoclonal antibodies: B8C4,
      C12E8, G6A2 and P4E5 were generated. Antibody G6A2 reacted strongly with PCMV
      infected cells as well as purified virions on ELISA and immunofluorescence.
      Western blot analysis, using sucrose gradient-purified virions, demonstrated that
      this mAb reacted specifically to a single protein with an apparent molecular
      weight of 71 kDa. The protein band was excised from the gel, purified and
      subjected to trypsin digestion followed by mass spectrometry. The protein
      sequences obtained were found to have identity to HCMV UL82 gene product.
      Sequence analysis indicated that it is the putative HCMV pp71 protein homolog of
      PCMV. G6A2 mAb did not cross-react with either human or murine recombinant pp71
      proteins expressed in mammalian cells.

PMID- 15582694
TI  - Construction and characterization of deltaretrovirus indicator cell lines.
AB  - The deltaretroviruses, which include bovine leukemia virus (BLV) and human T-cell
      leukemia virus types 1 and 2 (HTLV-1 and HTLV-2), replicate poorly in culture and
      the molecular details of their life cycles are limited. To facilitate the
      analysis of virus replication, mammalian cell lines were created with the long
      terminal repeats (LTRs) of each virus driving expression of the enhanced green
      fluorescent protein gene (egfp). The BLGFP, H1GFP and H2GFP cell lines detect
      virus infection by the expression of GFP via the transactivation of the LTR via
      the Tax protein of BLV, HTLV-1 or HTLV-2, respectively. GFP expression was
      measured by flow cytometry, yielding sensitive and rapid detection of virus
      infectivity. Interestingly, we observed that the Tax proteins of HTLV-1 and HTLV
      2 could transactivate the BLV LTR at levels that were comparable to that of BLV
      Tax. In contrast, the BLV Tax showed low levels of transactivation in H1GFP and
      H2GFP cells. HTLV-1 and HTLV-2 Tax proteins efficiently transactivated both the
      HTLV-1 and HTLV-2 LTRs. Finally, spinoculation of BLV resulted in only a two-fold
      increase in viral titer.

PMID- 15582695
TI  - A genotypic resistance assay for the detection of drug resistance in the human
      immunodeficiency virus type 1 envelope gene.
AB  - Since it is not clear yet whether enfuvirtide resistance is restricted to gp41,
      it was decided to develop a genotypic assay for the detection of drug resistance
      in the entire human immunodeficiency virus type 1 (HIV-1) env gene. Given the
      increasing prevalence of HIV-1 non-B subtypes in Europe, it is important to
      evaluate the performance of the assay on a panel of genetically divergent
      samples. A panel of 1 laboratory and 10 clinical isolates from 10 patients was
      tested, all enfuvirtide naive and chosen according to the subtype as determined
      in the pol region (A, B, C, H, CRF01-AE, CRF02-AG, CRF05-DF, CRF11-cpx and U),
      while their env sequences belonged to subtypes A, B, C, H, A/G recombinant, B/H
      recombinant, CRF01-AE, CRF02-AG, CRF05-DF and CRF11-cpx. The detection limits of
      the gp120 and the gp41 PCRs ranged between 500 and 5000 RNA copies/ml plasma. The
      highest sensitivity was obtained for the laboratory strain, whereas the detection
      limit for all patient samples, except for the subtype C sample, was 1000 RNA
      copies/ml. The numerous insertions and deletions in the gp120 gene, that were
      often present as quasi-species, necessitated the sequencing of cloned PCR
      products. The gp41 gene displayed less diversity and less insertions/deletions.
      Especially, the heptad repeat 1 was highly conserved and none of the enfuvirtide
      naive samples contained any of the already known enfuvirtide resistance mutations
      at amino acid positions 36-45. This study demonstrates that the assay is able to
      genotype genetically diverse HIV-1 strains with a good sensitivity.

PMID- 15582696
TI  - Expression and characterization of Gag protein of HIV-1(CN) in Pichia pastoris.
AB  - To express the core protein of HIV-1 of Chinese prevalent strain (HIV-1(CN)) in
      Pichia pastoris, the full-length gag gene was inserted into the secretory
      expression vector pHILS1. Linearized recombinant plasmid pHILGAG by SalI was
      electrotransformed into the yeast strain GS115, and the yeast transformants were
      identified by PCR. To induce the interest protein to be expressed, the PCR
      positive transformants were inoculated in the medium of BMGY and BMMY, mRNA of
      the strain was detected by RT-PCR, and the expressed protein was analyzed by SDS
      PAGE, Western blotting and thin layer scanning. mRNA (1.3kb) was amplified by RT
      PCR. SDS-PAGE and Western blotting analysis showed that the molecular mass of the
      expressed protein was 55kDa, which was similar to the expected value, and the
      expressed protein could react with McAb to HIV-1 p24. Thin layer scanning
      analysis demonstrated that the whole amount of the expressed protein was
      approximately 13% of the soluble protein in the supernatant. The recombinant
      yeast had good genetic stability. The optimal expression conditions of the
      engineering yeast were as follows: BMMY medium, 80-90% of dissolved oxygen, 1%
      methanol, and 3-day-cultivation course. Gag proteins were expressed under the
      optimal expression condition and purified via gel filtration chromatography. The
      purity of the interest protein was up to 85%. After the purified proteins were
      inoculated into BALB/c mice, the anti-HIV-1 antibodies in the immunized mice
      could be detected by Western blotting.

PMID- 15582697
TI  - A novel cell-based binding assay system reconstituting interaction between SARS
      CoV S protein and its cellular receptor.
AB  - Severe acute respiratory syndrome (SARS), a life-threatening disease, is caused
      by the newly identified virus SARS coronavirus (SARS-CoV). In order to study the
      spike (S) protein of this highly contagious virus, we established a clonal cell
      line, CHO-SG, from the Chinese hamster ovary cells that stably expresses C
      terminally EGFP-tagged SARS-CoV S protein (S-EGFP). The ectodomain of the S
      glycoprotein is localized on the surface of CHO-SG cells with N-acetyl
      glucosamine-terminated carbohydrate structure. CHO-SG cells associated tightly
      with Vero E6 cells, a SARS-CoV receptor (ACE2) expressing cell-line, and the
      interaction remained stable under highly stringent condition (1M NaCl). This
      interaction could be blocked by either the serum from a SARS convalescent patient
      or a goat anti-ACE2 antibody, indicating that the interaction is specific. A
      binding epitope with lesser degree of glycosylation and native conformation was
      localized by using rabbit anti-sera raised against five denatured recombinant S
      protein fragments expressed in Escherichia coli. One of the sera obtained from
      the fragment encompassing amino acids 48-358 significantly blocked the
      interaction between CHO-SG and Vero E6 cells. The region is useful for studying
      neutralizing antibodies in future vaccine development. This paper describes an
      easy and safe cell-based assay suitable for studying the binding between SARS-CoV
      S protein and its receptor.

PMID- 15582698
TI  - Serum hepatitis B DNA: stability in relation to multiple freeze-thaw procedures.
AB  - Quantitation of hepatitis B virus (HBV) DNA is often performed in specimens that
      have been frozen and thawed more than once. It is important to establish whether
      viral load measurements are affected by repeated freeze-thaw cycles. The effect
      of multiple freeze-thaw cycles on HBV DNA quantitation was carried out by testing
      serum specimens subjected to 1 (baseline) to 10 cycles with the appropriate
      Digene Hybrid Capture System. Five HBV DNA-positive samples were selected at
      random from sera with concentrations ranging from 7 pg/ml to 3529 pg/ml and they
      were frozen and thawed up to 10 cycles and then tested for changes in HBV DNA
      levels. Negative control and positive standards were tested in triplicate; and
      all specimens were tested in duplicate. The stability of HBV DNA in serum was
      evaluated by scattergram analysis by determining the number of samples showing a
      > or =20% change in HBV DNA levels after freeze-thaw cycles. With the exception
      of one sample (7 pg/ml) 10 cycles of freezing and thawing did not change
      significantly the HBV DNA quantity in any of the samples tested. The results
      showed that the quantity of HBV DNA in four of five serum specimens subjected up
      to 10 freeze-thaw cycles was stable.

PMID- 15582699
TI  - Absolute quantitation of Marek's disease virus genome copy number in chicken
      feather and lymphocyte samples using real-time PCR.
AB  - A real-time PCR method was developed, optimised and validated, to enable
      quantitation of Marek's disease virus genomes as copy number per million host
      cells. The duplex PCR measured the virus meq gene and host ovotransferrin gene in
      a single reaction enabling correction for differences in amount of sample DNA
      added. A bacterial artificial chromosome (BAC) clone of the virus genome, and a
      plasmid (pGEM-T-ovo) bearing a fragment of the chicken ovotransferrin gene, were
      used to quantify virus and host genomes respectively. This sensitive and
      reproducible assay was established initially using chicken lymphocyte DNA, then
      adapted for feather tip DNA by inclusion of bovine serum albumin in the reaction
      to overcome inhibition by melanin. The principal advantages are: (1)
      determination of absolute virus genome copy number enabling meaningful comparison
      between samples; (2) expression of copy number per million cells, allowing direct
      correlation with plaque assays; (3) using BAC-cloned whole virus genome as a
      standard potentially enables any virus gene to be used as the PCR target. This is
      the first report of quantitation of MDV genomes in feather tips, and application
      of this assay could significantly further our understanding of pathogenesis,
      spread, diagnosis, genetic resistance and vaccinal control of Marek's disease.

PMID- 15582700
TI  - Gene transfer into hepatocytes mediated by herpes simplex virus-Epstein-Barr
      virus hybrid amplicons.
AB  - Gene transfer into hepatocytes is highly desirable for the long-term goal of
      replacing deficient proteins and correcting metabolic disorders. Vectors based on
      herpes simplex virus type-1 (HSV-1) have been demonstrated to mediate efficient
      gene transfer into hepatocytes both in vitro and in vivo. Large transgene
      capacity and extrachromosomal persistence make HSV-1/EBV hybrid amplicon vectors
      an attractive candidate for hepatic gene replacement therapy. To assess liver
      directed gene transfer, we constructed (i) a conventional HSV-1 amplicon vector
      encoding a secreted reporter protein (secreted alkaline phosphatase, SEAP) under
      the control of the HSV-1 immediate-early 4/5 promoter; (ii) a HSV-1 amplicon
      encoding SEAP under the control of the artificial CAG promoter (the chicken beta
      actin promoter and cytomegalovirus (CMV) immediate-early enhancer); and (iii) a
      HSV-1/EBV hybrid amplicon, also encoding SEAP under the control of the CAG
      promoter. While all three vector constructs yielded high SEAP concentrations in
      vitro and in vivo, use of HSV-1/EBV hybrid amplicon vectors significantly
      prolonged the duration of gene expression. Using conventional amplicon vectors in
      cultured hepatocytes, SEAP was detected for two weeks, whereas SEAP was detected
      for at least six weeks when HSV-1/EBV amplicons were used. Intraparenchymal
      injection into the liver of SICD mice yielded high (up to 77 ng of SEAP per
      milliliter serum) and sustained (greater than three weeks) expression of SEAP.
      Serum transaminases (ALT/AST) were measured at different time points to monitor
      for hepatocellular damage. While initially elevated four times above baseline,
      the transaminase levels returned to normal after three to seven days. These
      results demonstrate the usefulness of HSV-1-based amplicons and SEAP for the
      evaluation of gene replacement strategies in the liver.

PMID- 15582701
TI  - The use of real-time RT-PCR (TaqMan) and post-ELISA virus release for the
      detection of Beet necrotic yellow vein virus types containing RNA 5 and its
      comparison with conventional RT-PCR.
AB  - Real-time RT-PCR (TaqMan) assays were developed for the specific detection of
      Beet necrotic yellow vein virus (BNYVV). The two assays designed were a broad
      spectrum one that detected RNA 2 from all types and a second designed to detect
      types containing RNA 5. The assays were validated against a range of different
      isolates from Europe and the Far East. These real-time assays were compared to a
      conventional RT-PCR assay for the detection of RNA 5. Sensitivity comparisons
      showed that for the detection of RNA 5, TaqMan was 10,000 times more sensitive
      than the conventional RT-PCR assay. Further improvements were made to the test
      procedure by using post-ELISA virus release (VR), as an alternative to RNA
      extraction. This significantly increased the speed of processing samples and
      reduced the staff input required, allowing the TaqMan assay to be used routinely
      as part of an annual survey of UK field samples.

PMID- 15582702
TI  - Consensus-degenerate hybrid oligonucleotide primers (CODEHOP) for the detection
      of novel papillomaviruses and their application to esophageal and tonsillar
      carcinomas.
AB  - Human papillomaviruses (HPVs) have been identified in 99% of cervical tumors.
      Considerable speculation exists about the role of HPV in cancer at other sites,
      such as skin, esophagus, and lung. One barrier to the study of HPV in
      extragenital tumors may be the inability to detect novel HPV types. Our objective
      was to design broad-range primers for detecting papillomaviruses from any group
      in the HPV Sequence Database. Complete L1 protein sequences were aligned and 11
      blocks of conserved protein sequences were identified. Primers were designed in
      the corresponding nucleotide regions of five blocks. One pair of primers, ME and
      MH, derived from blocks E and H, appeared promising when compared with
      established consensus primers. To improve the sensitivity for detection of
      multiple papillomavirus types, ME/MH primers were split into several primers with
      the 5' regions matched to individual papillomavirus supergroups. Compared with
      the commonly used MY09/11 primer set, our primer sets were broader in range and
      more sensitive against most papillomavirus types tested. Application of these
      primers to esophageal and tonsillar carcinomas identified no novel HPV types but
      confirmed a high level of sensitivity for detecting HPV from these clinical
      samples. These primers should facilitate the search for novel papillomaviruses.

PMID- 15582703
TI  - Biolistic inoculation of gladiolus with cucumber mosaic cucumovirus.
AB  - A new method of inoculation of gladiolus with cucumber mosaic virus (CMV) was
      developed using the Bio-Rad Helios Gene Gun System. This method circumvents the
      traditional use of aphids to transmit CMV, a virus that is mechanically
      transmissible to many plant species but only with difficulty to gladiolus.
      Cartridges containing virus-coated gold microcarriers were prepared and the virus
      shot into Nicotianabenthamiana leaves and gladiolus corms and cormels. The
      biolistic procedure successfully transmitted three CMV isolates, two from
      serogroup I and one from serogroup II. Survival rates of two cultivars of
      gladiolus cormels and corms in sterile and non-sterile environments were
      compared. Infection rates of 100% were obtained when as little as 2 microg of
      virus was used in cartridge preparation. CMV remained viable after the cartridges
      were stored for many months at 4 degrees C.

PMID- 15582704
TI  - On the TATA box and transcriptional start site of gE gene of pseudorabies virus:
      a comparison of three methods.
AB  - Using the upstream region of glycoprotein E gene of pseudorabies virus (PRV) as a
      model, a method based on reverse transcriptase-polymerase chain reaction (RT-PCR)
      for the determination of transcriptional start site was developed. The
      conventional primer extension method was used to determine the start site.
      Comparing the results obtained by these two methods, a good agreement on the
      location of start site was achieved. In addition, a computer program was used to
      predict the transcriptional start site, and the predicted site was found to be
      close to the two sites obtained by experiments. Based on the transcriptional
      start site data and on the general knowledge of the eukaryotic gene, the TATA box
      of gE gene was assigned at approximately 33 bp upstream to the start site.

PMID- 15582705
TI  - Differentiation of Cucumber mosaic virus isolates by hybridization to
      oligonucleotides in a microarray format.
AB  - A system for microarrays was developed to detect and differentiate Cucumber
      mosaic virus (CMV) serogroups and subgroups. The coat protein genes of 14
      different isolates were amplified using cy3-labelled generic but species-specific
      primers. These amplicons were hybridized against a set of five different serotype
      and subgroup specific 24-mer oligonucleotides bound to an aldehyde-coated glass
      slide via an aminolinker. The results of the hybridization revealed that the
      method allowed a clear differentiation of the 14 different CMV isolates into the
      serogroupes 1 and 2, and in addition was able to assign 9 out of 10 different
      serogroup 1 isolates correctly into subgroups 1a and 1b. This differentiation was
      not possible by RFLP analysis with the restriction enzyme MspI. The use of
      amplicons larger than 700 base pairs and their successful differentiation by
      hybridization to specific oligonucleotides opens avenues to highly parallel, yet
      sensitive assays for plant viruses.

PMID- 15582706
TI  - Development of a reverse transcription-PCR assay to detect porcine circovirus
      type 2 transcription as a measure of replication.
AB  - Porcine circovirus type 2 (PCV2) is a non-enveloped, single-stranded, circular
      DNA virus. In situ hybridization and PCR assays have detected PCV2 DNA in
      multiple organs and cell types from infected pigs; however, it is not clear if
      this represents replicating virus or virion DNA. We describe the development of a
      single-tube RT-PCR assay to differentiate PCV2 replication products and virus
      DNA. Primers targeted to the open-reading frame 2 (ORF2) of PCV2 were designed to
      amplify both virus DNA (984 bp) and the spliced Cap mRNA (594 bp). The 984 bp
      fragment, but not the 594 bp fragment, was amplified from PCV2 stock, confirming
      that the spliced Cap mRNA was not present in the PCV2 stock. The 594 bp fragment
      was amplified from DNase-treated RNA extracted from PCV2-infected PK-15 cells,
      and was detected as early as 14 h post-infection. No products were amplified from
      either the PCV1 stock or PCV1-infected PK-15 cells, or from cells infected with
      UV-inactivated PCV2. Therefore, the presence of the 594 bp fragment is specific
      for PCV2 replication. This assay will be useful in assessing cell populations
      that support PCV2 replication in vivo or in vitro and advance the understanding
      of PCV2 replication and pathogenesis.

PMID- 15582707
TI  - Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid
      mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment.
AB  - A concentration gradient of stromal-cell-derived factor-1alpha (SDF-1alpha) is
      the major mechanism for homing of haematopoietic stem cells (HSCs) in bone
      marrow. We tested the hypothesis that a gene therapy using SDF-1alpha can enhance
      HSCs recruiting to the heart upon myocardial infarction (MI). Adult mice with
      surgically induced myocardial ischemia were injected intramyocardially with
      either saline (n=12) or SDF-1alpha plasmid (n=12) in 50 microl volume in the
      ischemic border zone of the infarcted heart 2 weeks after myocardial infarction.
      Donor Lin-c-kit+ HSCs from isogenic BalB/c mice were harvested, sorted through
      magnetic cell sorting (MACS) and labeled with PKH26 Red. Three days after plasmid
      or saline injection, 1x10(5) labeled cells were injected intravenously (i.v.)
      into saline mice (n=4) and SDF-1alpha plasmid mice (n=4). The hearts and other
      tissue were removed for Western blot assay 2 weeks after plasmid or saline
      treatment. The labeled Lin-c-kit+ cells were identified with immunofluoresent
      staining and endogenous c-kit+ cells were identified by immunohistochemical
      staining. In mice killed at 1 month postinfarct, Western blot showed higher
      levels of SDF-1alpha expression in SDF-1alpha-treated mouse ischemic hearts
      compared to saline-treated hearts and other tissues. In the SDF-1alpha plasmid
      treated hearts, SDF-1alpha is overexpressed in the periinfarct zone. The labeled
      stem cells engrafted to the SDF-1alpha positive site in the myocardium. There was
      also evidence for endogenous stem cell recruiting. The density of c-kit+ cells in
      border zone, an index of endogenous stem cell mobilization, was significantly
      higher in the SDF-1alpha-treated group than in the saline group (14.63+/-1.068
      cells/hpf vs. 11.31+/-0.65 cells/hpf, P=0.013) at 2 weeks after SDF-1alpha or
      saline treatment. Following myocardial infarction, treatment with SDF-1alpha
      recruits stem cells to damaged heart where they may have a role in repairing and
      regeneration. The gene therapy with an SDF-1alpha vector offers a promising
      therapeutic strategy for mobilizing stem cells to the ischemic myocardium.

PMID- 15582708
TI  - Neuropeptide Y induces cardiomyocyte hypertrophy via calcineurin signaling in
      rats.
AB  - Neuropeptide Y (NPY) has been shown to participate in cardiac hypertrophy.
      However, the mechanisms by which NPY induces cardiomyocyte hypertrophy are poorly
      understood. This study tested the hypothesis that NPY induces cardiomyocyte
      hypertrophy through Ca2+/CaM-dependent calcineurin (CaN) pathway in cultured
      neonatal rat cardiomyocytes. After 24-h treatment, NPY (100 nM) significantly
      increased 3H-leucine incorporation and c-Jun mRNA expression, concomitant with
      augment of CaN activity and protein level in cardiomyocytes compared to those
      cells without NPY treatment. The enhancement of 3H-leucine incorporation and c
      Jun mRNA expression in cardiomyocytes treated with NPY were markedly inhibited by
      cyclosporine A (CsA), a selective inhibitor of CaN. We also investigated the
      effect of NPY on intracellular Ca2+ level in cardiomyocytes. There were no
      obvious changes in intracellular Ca2+ level of cytoplasm and nucleus in
      cardiomyocytes treated with NPY (100 nM) for 10 min. However, NPY significantly
      increased intracellular Ca2+ level of cytoplasm and nucleus in cardiomyocytes
      after 24-h treatment. The result suggested that NPY could induce hypertrophy of
      cardiomyocytes via Ca2+/CaM-dependent CaN signal pathway. The enhancement of
      [Ca2+]i caused by NPY may activate CaN signal pathways to mediate cardiac
      hypertrophy.

PMID- 15582709
TI  - PTH-related protein enhances LoVo colon cancer cell proliferation, adhesion, and
      integrin expression.
AB  - Parathyroid hormone-related protein (PTHrP) has been localized in human colon
      cancer tissue and cell lines. Tumor cell adhesion to extracellular matrix (ECM)
      proteins plays a major role in the invasion and metastasis of tumor cells, and is
      mediated via integrin subunits. The LoVo human colon cancer cell line was used as
      a model system to study the effects of PTHrP on cell proliferation and adhesion
      to ECM proteins found in normal liver. Clones of LoVo cells engineered to
      overexpress PTHrP by stable transfection with a PTHrP cDNA showed enhanced cell
      proliferation vs. control (empty vector-transfected) cells. PTHrP-overexpressing
      cells also showed significantly higher adhesion to collagen type I, fibronectin,
      and laminin, and enhanced expression of the [symbol: see text] integrin subunits.
      These results indicate that PTHrP may play a role in colon cancer invasion and
      metastasis by increasing cell proliferation and adhesion to the ECM via
      upregulation of proinvasive integrin expression.

PMID- 15582710
TI  - Chronic infusion of angiotensin-(1-7) reduces heart angiotensin II levels in
      rats.
AB  - We tested the hypothesis that the actions of Angiotensin (Ang)-(1-7) in the heart
      could involve changes in tissue levels of Ang II. This possibility was addressed
      by determining the effect of chronic infusion of Ang-(1-7) on plasma and tissue
      angiotensins. Ang-(1-7) was infused subcutaneously (osmotic minipumps) in Wistar
      rats. Angiotensins were determined by radioimmunoassay (RIA) in plasma, heart,
      and kidney. Tissue and plasma angiotensin-converting enzyme (ACE) activity and
      plasma renin activity (PRA) were also measured. Cardiac and renal ACE2 mRNA
      levels and cardiac angiotensinogen mRNA levels were assessed by semi-quantitative
      polymerase chain reaction (PCR). AT1 receptor number was evaluated by
      autoradiograph. Chronic infusion of Ang-(1-7) (2 microg/h, 6 days) produced a
      marked decrease of Ang II levels in the heart. A less pronounced but significant
      decrease of Ang-(1-7) was also observed. No significant changes were observed for
      Ang I. Ang II was not altered in the kidney. In this tissue, a significant
      increase of Ang-(1-7) and Ang I concentration was observed. A significant
      increase of plasma Ang-(1-7) and Ang II was also observed. Ang-(1-7) infusion did
      not change ACE activity or PRA. A selective slight significant increase in ACE2
      expression in the heart was observed. Heart angiotensinogen mRNA as well as the
      number of Ang II binding sites did not change. These results suggest that AT1
      receptors-independent changes in heart Ang II concentration might contribute for
      the beneficial effects of Ang-(1-7) in the heart. Moreover, these results
      reinforce the hypothesis that this angiotensin plays an important site-specific
      role within the renin-angiotensin system.

PMID- 15582711
TI  - A proline-rich polypeptide complex and its nonapeptide fragment inhibit nitric
      oxide production induced in mice.
AB  - A proline-rich polypeptide complex (PRP) isolated from ovine colostrum shows
      immunoregulatory and procognitive activities. It shows beneficial effects in
      Alzheimer's disease (AD) patients when orally administered in the form of tablets
      called Colostrinin. The mechanism of action of PRP/Colostrinin in AD has not been
      yet clarified. It is known that oxidative stress and overproduction of NO may
      enhance neurodegenerative processes. PRP regulates the secretion of cytokines,
      inhibits NO and O2- release in cell cultures. Since the results on isolated cells
      or cell lines frequently do not reflect the events in vivo, the effect of PRP and
      its nonapeptide fragment (NP) on the level of NO2- in sera of mice untreated or
      intraperitoneally treated with LPS was studied. PRP and NP did not induce
      production of NO. However, when applicated 6 h after LPS, they inhibited the
      release of NO induced by LPS in about 30-50%. The results in vivo presented in
      this paper confirm the results obtained in cell cultures and indicate that the
      beneficial effects of PRP/Colostrinin observed in AD patients may be, among
      others, due to an inhibition of overproduction of NO.

PMID- 15582712
TI  - eNOS, nNOS, cGMP and protein kinase G mediate the inhibitory effect of
      pancreastatin, a chromogranin A-derived peptide, on growth and proliferation of
      hepatoma cells.
AB  - Pancreastatin (PST), a chromogranin A-derived peptide, has an anti-insulin
      metabolic effect and inhibits growth and proliferation by producing nitric oxide
      (NO) in HTC rat hepatoma cells. When NO production is blocked, a proliferative
      effect prevails due to the activation a Galphaq/11-phospholipase C-beta (PLC
      beta) pathway, which leads to an increase in [Ca2+]i, protein kinase C (PKC) and
      mitogen-activated protein kinase (MAPK) activation. The aim of the present study
      was to investigate the NO synthase (NOS) isoform that mediates these effects of
      PST on HTC hepatoma cells and the possible roles of cyclic GMP (cGMP) and cGMP
      dependent protein kinase. DNA and protein synthesis in response to PST were
      measured as [3H]-thymidine and [3H]-leucine incorporation in the presence of
      various pharmacological inhibitors: N-monomethyl-L-arginine (NMLA, nonspecific
      NOS inhibitor), L-NIO (endothelial nitric oxide synthase (eNOS) inhibitor),
      espermidine (neuronal nitric oxide synthase (nNOS) inhibitor), LY83583 (guanylyl
      cyclase inhibitor), and KT5823 (protein kinase G inhibitor, (PKG)). L-NIO,
      similarly to NMLA, reverted the inhibitory effect of PST on hepatoma cell into a
      stimulatory effect on growth and proliferation. Nevertheless, espermidine also
      prevented the inhibitory effect of PST, but there was no stimulation of growth
      and proliferation. When guanylyl cyclase activity was blocked, there was again a
      reversion of the inhibitory effect into a stimulatory action, suggesting that the
      effect of NO was mediated by the production of cGMP. PKG inhibition prevented the
      inhibitory effect of PST, but there was no stimulatory effect. Therefore, the
      inhibitory effect of PST on growth and proliferation of hepatoma cells may be
      mainly mediated by eNOS activation. In turn, the effect of NO may be mediated by
      cGMP, whereas other pathways in addition to PKG activation seem to mediate the
      inhibition of DNA and protein synthesis by PST in HTC hepatoma cells.

PMID- 15582713
TI  - Glucocorticoid responses to stress in castrate and testosterone-replaced rams.
AB  - Stress is an important contributor to cardiovascular disease and to reduced
      immunity and fertility. As the role of androgens in stress is uncertain, we
      investigated the effects of testosterone (T) on hormonal responses to stress in
      conscious Romney Marsh wethers. Six T-treated sheep and six control sheep were
      stressed by exposure to a psychological and a metabolic stimulus. Baseline
      glucose levels were significantly lower in the treated animals compared with
      controls (p=0.002). T treatment significantly attenuated ACTH (p<0.01) and
      cortisol (p<0.05) responses to metabolic stress. Following psychological stress,
      ACTH responses were significantly lower in treated sheep compared with controls
      (p<0.05), but differences in mean cortisol responses did not reach significance.
      There were no significant differences in epinephrine or norepinephrine responses
      following either stressor. We conclude that T replacement in wethers lowers
      glucose and attenuates responses to metabolic and psychological stress. While the
      implications of these results for human physiology require further studies, they
      suggest that male hypogonadism may play a role in determining the risk of
      cardiovascular disease and diabetes.

PMID- 15582714
TI  - Central and peripheral cardiovascular actions of apelin in conscious rats.
AB  - APJ was cloned as an orphan G protein-coupled receptor and shares a close
      identity with angiotensin II type 1 receptor (AT1R). Apelin is a peptide that has
      recently been identified as an endogenous ligand of the APJ. Apelin and APJ mRNA
      are expressed in peripheral tissue and the central nervous system. However,
      little is known about the effects of apelin in cardiovascular regulation. To
      examine the central and peripheral role of apelin, we injected the active
      fragment of apelin [(Pyr1)apelin-13] intracerebroventricularly (ICV, 5 and 20
      nmol, n=6) or intravenously (IV, 20 and 50 nmol, n=4 or 5) in conscious rats. ICV
      injection of (Pyr1)apelin-13 dose-dependently increased mean arterial pressure
      (MAP) and heart rate (HR) (19+/-3 mm Hg and 162+/-26 bpm at 20 nmol).
      Pretreatment with ICV injection of the AT1R antagonist (CV-11974, 20 nmol) did
      not alter the apelin-induced increase in MAP and HR. IV injection of (Pyr1)apelin
      13 also dose-dependently increased MAP and HR (13+/-2 mm Hg and 103+/-18 bpm at
      50 nmol); however, the peripheral effects of apelin were relatively weak compared
      to its central effects. Expression of c-fos in the paraventricular nucleus (PVN)
      of hypothalamus was increased in the rat that received ICV injection of
      (Pyr1)apelin-13 but not in the rat that received IV injection of (Pyr1)apelin-13.
      These results suggest that apelin plays a role in both central and peripheral
      cardiovascular regulation in conscious rats, and that the cardiovascular effects
      of apelin are not mediated by the AT1R.

PMID- 15582715
TI  - Proteinase-activated receptors (PARs)--the PAR3 Neo-N-terminal peptide TFRGAP
      interacts with PAR1.
AB  - Thrombin activates proteinase-activated receptor (PAR)1, PAR3 and PAR4 by a
      unique mechanism that involves cleavage of the receptor and exposure of a new N
      terminal domain acting as a tethered ligand. Synthetic peptides based on the
      proteolytically revealed receptor sequence can selectively activate PAR1 or PAR4
      independently of receptor cleavage. However, corresponding peptides for PAR3 have
      not been identified thus far. Here, we demonstrate that the synthetic peptide
      TFRGAP representing the 1st six residues of the new amino terminus of PAR3
      induced ERK activation in human A-498 carcinoma cells endogeneously expressing
      PAR1 and PAR3. This effect was completely abolished by single alanine
      substitution at positions 3, 4 and 6 in the peptide. Since the specific PAR1
      antagonist RWJ 56110 completely abolished TFRGAP-induced ERK activation in A-498
      cells we speculate that TFRGAP does signal MAPK via interaction with PAR1. This
      was underlined by experiments on PAR1-/- mouse lung fibroblasts (KOLF cells) that
      stably overexpress human PAR1 and PAR3, respectively. While TFRGAP was without
      effect on ERK activation in PAR3+ KOLF cells, it induced MAPK activation in KOLF
      cells transfected with PAR1. These studies provide evidence that analogues of the
      PAR3 tethered ligand can mediate cell signaling by interaction with PAR1-type
      thrombin receptors.

PMID- 15582716
TI  - Behavioural characterisation of young adult transgenic mice overexpressing
      galanin under the PDGF-B promoter.
AB  - The behavioural phenotype of transgenic mice (3- to 5-months old) overexpressing
      galanin (GalOE) under the platelet-derived growth factor B (PDGF-B) promoter was
      evaluated in a battery of tests, including open field, locomotor cages, light
      dark exploration test, elevated plus-maze and the Porsolt forced swim test.
      Learning and memory were assessed in the passive avoidance and the Morris water
      maze tasks. No difference between genotypes was found in exploratory activity in
      the open field. GalOE mice showed a slight increase in spontaneous locomotor
      activity assessed in the locomotor cages, but the amphetamine-induced increase in
      locomotor activity was somewhat lower in GalOE mice. Anxiety-like behaviour in
      the three different tests including open field, light-dark exploration and
      elevated plus-maze did not differ between genotypes. In the Porsolt forced swim
      test, GalOE mice displayed an increased time of immobility, indicative of
      increased learned helplessness possibly reflecting increased stress
      susceptibility and/or depression-like behaviour. GalOE mice showed normal
      learning and memory retention in the passive avoidance and the Morris water maze
      tasks. These data support the hypothesis that galanin may have a role in
      functions related to mood states including affective disorders.

PMID- 15582717
TI  - Neuropeptide Y Y5 receptors inhibit kindling acquisition in rats.
AB  - Neuropeptide Y inhibits neuronal excitability and seizures in various
      experimental models. This peptide delays kindling epileptogenesis but the
      receptors involved in this action are unknown. We have studied the role of Y5
      receptors in kindling using the selective antagonist GW438014A (IC50=210 nM), a
      small heterocycle molecule that crosses the blood-brain barrier, and the
      selective peptide agonist Ala31Aib34 NPY (IC50=6.0 nM). Intraperitoneal injection
      of GW438014A (10 mg/kg), 30 min before the beginning of a rapid-kindling
      protocol, significantly accelerated the rate of kindling acquisition as compared
      to vehicle-injected rats. Thus, the number of electrical stimuli required to
      reach stages 3 and 4-5 of kindling were reduced by 50% and 25%, respectively. The
      average afterdischarge duration in the stimulated hippocampus was prolonged by 2
      fold. Conversely, kindling rate was delayed by intracerebroventricular
      administration of 24 nmol Ala31Aib32 NPY. Thus, the number of stimuli necessary
      to reach stages 2 and 3 of kindling was increased by 3- and 4-fold, respectively.
      During the stimulation protocol (40 stimuli) none of the rats treated with the Y5
      agonist showed stages 4-5 seizures. Twenty-four hours after the last kindling
      stimulation, thus during the re-test session, Y5 agonist- or antagonist-treated
      rats had stages 4-5 seizures as their controls. In rats treated with both the
      antagonist and the agonist, kindling rate was similar to vehicle-injected rats.
      These data indicate that Y5 receptors mediate inhibitory effects of NPY in
      kindling and display anticonvulsant rather then antiepileptogenic effects upon
      agonist stimulation.

PMID- 15582718
TI  - The somatostatin subtype-2 receptor antagonist, BIM-23627, improves the catabolic
      effects induced by long-term glucocorticoid treatment in the rat.
AB  - BIM-23627 is a synthetic peptide with "in vitro" and "in vivo" properties
      consistent with a pure sst2 antagonist. The aim of the present study was to
      evaluate the effects of long-term administration of BIM-23627 and the combined
      effects of BIM-23627 and dexamethasone (DEX) on the somatotropic axis, including
      growth, epididymal fat accumulation, glucose homeostasis and insulin activity, in
      young male rats. Beginning on day 23 of age, 16 animals were treated daily with
      saline or DEX (40 microg/kg/daily). Each group was subdivided into two paired
      groups and treated with either vehicle or BIM-23627 (0.5 mg/kg, t.i.d.). The
      treatment period lasted 31 days. The animals were killed by decapitation; trunk
      blood and pituitaries were collected for the determination of hormone
      concentrations and GH mRNA expression, respectively. Based on plasma GH and IGF-I
      concentrations and GH mRNA expression in the pituitary, BIM-23627 was able to
      counteract the inhibitory effects of DEX on the somatotropic axis; however, only
      a partial reversal of somatic growth inhibition was observed. DEX-treated rats
      remained euglycemic, but their insulin levels were significantly increased,
      indicating an incipient insulin resistance. Although BIM-23627 itself tended to
      increase insulin concentration in saline-treated rats, its administration to DEX
      treated rats reduced insulin levels (saline: 25+/-3; DEX: 55+/-16*; DEX+BIM
      23627: 34+/-5; BIM-23627: 38+/-7 microIU/ml; *P<0.05 vs. saline), apparently
      improving the degree of insulin sensitivity. DEX administration significantly
      reduced circulating ghrelin, whereas the sst2 antagonist had no significant
      effect. An inverse correlation was found between ghrelin concentrations and
      plasma insulin levels. Both rats receiving DEX and rats receiving BIM-23627 had
      decreased plasma concentration of total testosterone (P<0.05); however, the
      effects of DEX and BIM-23627 were not additive. In conclusion, BIM-23627 may
      represent a new pharmacological agent to reduce the suppression of the GH-IGF-I
      axis in long-term GC treated patients and enhance insulin sensitivity. Further
      studies are required in order to fully optimize the SSTR-2 antagonist-induced
      reversal of DEX-induced somatic growth inhibition.

PMID- 15582719
TI  - Involvement of CGRP in the inhibitory effect of rutaecarpine on vasoconstriction
      induced by anaphylaxis in guinea pig.
AB  - Previous investigations have indicated that calcitonin gene-related peptide
      (CGRP), a principal transmitter in capsaicin-sensitive sensory nerves, could
      alleviate cardiac anaphylaxis injury. Rutaecarpine relaxes vascular smooth by
      stimulation of CGRP release via activation of vanilloid receptor subtype 1 (VR1).
      In the present study, we examined the role of capsaicin-sensitive sensory nerves
      in anaphylactic vessels and the effect of rutaecarpine on antigen-challenged
      constriction in the guinea pig isolated thoracic aorta. The aortas were
      challenged with 0.01 mg/ml bovine serum albumin, and the tension of aorta rings
      was continuously monitored. The amount of CGRP released from thoracic aortas was
      determined in the absence or presence of rutaecarpine. Antigen challenge caused a
      vasoconstrictor response concomitantly with an increase in the release of CGRP
      from the isolated thoracic aorta, and the vasoconstrictor responses were
      potentiated by CGRP8-37 (10 microM) or capsaicin (1 microM). Pretreatment with
      diphenhydramine (1 microM) markedly decreased antigen-challenged
      vasoconstriction. Acute application of capsaicin (0.03 or 0.1 microM)
      significantly inhibited vasoconstrictor responses. Pretreatment with rutaecarpine
      (10 or 30 microM) significantly increased CGRP release concomitantly with
      decrease in antigen-challenged vasoconstriction, which was abolished by CGRP8-37
      (10 microM) or capsazepine (10 microM). The present results suggest that an
      increase in the release of CGRP during vascular anaphylaxis may be a beneficial
      compensatory response, and that rutaecarpine inhibits antigen-challenged
      vasoconstriction, which is related to stimulation of endogenous CGRP release via
      activation of VR1.

PMID- 15582720
TI  - Calcitonin gene-related peptide does not interact with sympathetic activity in
      myocardial ischemia.
AB  - The aim of the present study was to assess whether calcitonin gene-related
      peptide (CGRP) modulates exocytotic norepinephrine release in ischemic
      myocardium. In isolated rat hearts subjected to 30 min of low flow ischemia, CGRP
      release increased 2.8-fold whereas stimulation-induced norepinephrine release
      decreased 4.1-fold. Pretreatment of rats with capsaicin almost completely
      depleted cardiac CGRP stores; however, suppression of norepinephrine release by
      30 min of low flow ischemia was not affected. At normal flow, exogenous CGRP (5
      micromol l-1) had no effect on norepinephrine release. These findings suggest
      that CGRP release from sensory neurons does not interact with the cardiac
      sympathetic system during myocardial ischemia.

PMID- 15582721
TI  - Overexpression of a dominant negative GIP receptor in transgenic mice results in
      disturbed postnatal pancreatic islet and beta-cell development.
AB  - The expression of a dominant negative glucose-dependent insulinotropic
      polypeptide receptor (GIPRdn) under the control of the rat pro-insulin gene
      promoter induces severe diabetes mellitus in transgenic mice. This study aims to
      gain further insight into the effect of the expression of a dominant negative
      GIPR on glucose homeostasis and postnatal development of the endocrine pancreas.
      The diabetic phenotype of GIPRdn transgenic animals was first observed between 14
      and 21 days of age (urine glucose>1000 mg/dl). After onset of diabetes, serum
      glucose was significantly higher and insulin values were significantly lower in
      GIPRdn transgenic mice vs. non-transgenic littermate controls. Morphometric
      studies of pancreatic islets and their endocrine cell types were carried out at
      10, 30 and 90 days of age. The total islet and total beta-cell volume of
      transgenic mice was severely reduced as compared to control mice, irrespective of
      the age at sampling (p<0.05). The total volume of isolated insulin positive cells
      that were not contained within established islets was significantly reduced in
      transgenic mice, indicating disturbed islet neogenesis. These findings
      demonstrate in vivo evidence that intact signaling of G-protein coupled receptors
      is involved in postnatal islet and beta-cell development and neogenesis of the
      pancreatic islets.

PMID- 15582722
TI  - Protective effect of central thyrotropin-releasing hormone analog on cerulein
      induced acute pancreatitis in rats.
AB  - Central neuropeptides play a role in many physiological functions through the
      autonomic nervous system. We have recently demonstrated that central injection of
      a thyrotropin-releasing hormone (TRH) analog increases pancreatic blood flow
      through vagal and nitric oxide-dependent pathways. In this study, the central
      effect of a TRH analog on experimental acute pancreatitis was investigated in
      rats. Acute pancreatitis was induced by two intraperitoneal injections of
      cerulein (40 microg/kg) at 1-h interval. Either stable TRH analog, RX 77368 (5
      100 ng), or saline was injected intracisternally 15 min before the first cerulein
      injection under ether anesthesia. Serum amylase level was measured before and 5 h
      after the first cerulein injection. Pancreatic wet/dry weight ratio and
      histological changes were also evaluated. Intracisternal TRH analog inhibited
      cerulean-induced elevation of serum amylase level, increase in pancreatic wet/dry
      weight ratio and pancreatic histological changes, such as interstitial edema,
      inflammation and vacuolization. The pancreatic cytoprotection induced by central
      TRH analog was abolished by subdiaphragmatic vagotomy and N(G)-nitro-L-arginine
      methyl ester (L-NAME), but not by 6-hydroxydopamine (6-OHDA). Intravenous
      administration of the TRH analog did not influence cerulein-induced acute
      pancreatitis. These results indicate that the TRH analog acts in the central
      nervous system to protect against acute pancreatitis through vagal and nitric
      oxide-dependent pathways.

PMID- 15582723
TI  - Coexpression of preprotachykinin A and B transcripts in the bovine corpus luteum
      and evidence for functional neurokinin receptor activity in luteal endothelial
      cells and ovarian macrophages.
AB  - Nonneuronal cell sources of tachykinins, such as substance P (SP) and neurokinin
      B (NKB), have been demonstrated in leukocytes, endothelial cells and endocrine
      cells, and may play a role in corpus luteum (CL) development. For this reason, we
      analyzed mRNA presence for the two tachykinin precursors together with the
      neurokinin-1 receptor and the neurokinin-3 receptor (NK-1R and NK-3R, preferred
      by SP and NKB, respectively) in bovine CL at various stages in the luteal phase.
      Using the RT-PCR technique, we detected coexpression for the preprotachykinin A
      gene (PPT-A), which encodes SP and neurokinin A (NKA), and the preprotachykinin B
      gene (PPT-B) for NKB in the CL at the development, secretion and regression
      stages. Coexpression was also noted for NK-1R and NK-3R gene transcripts.
      Cultures of endothelial cells (ECs) derived from bovine CL expressed NK-1R and NK
      3R mRNA, as did ovarian macrophages. Agonist treatment induced a stronger
      intracellular calcium ([Ca2+]i) increase after activation of NK-1R compared to NK
      3R, a result that we verified by calcium imaging. This is the first evidence for
      functional tachykinin receptor activity in luteal ECs and ovarian macrophages
      from bovine CL.

PMID- 15582724
TI  - Leptin ameliorates burn-induced multiple organ damage and modulates postburn
      immune response in rats.
AB  - The present study was designed to determine whether exogenous leptin reduces
      remote organ injury in the rats with thermal burn trauma. Leptin (10 microg/kg)
      or saline was administered intraperitoneally after burn injury, and the rats were
      decapitated at either 6 or 24 h. Plasma samples of 24-h burn group were assayed
      for the determination of monocyte and neutrophil apoptosis. Thermal injury
      increased tissue-associated myeloperoxidase (MPO) activity and microscopic damage
      scores in the lung, liver, stomach, colon and kidney of both 6- and 24-h burn
      groups. In the 6-h burn group, leptin reduced microscopic damage score in the
      liver and kidney only, while damage scores in the 24-h burn group were reduced in
      all the tissues except the lung. Also, in both burn groups, leptin reduced
      elevated MPO activity in all tissues except the lung. The percentage of
      mononuclear cells was significantly reduced at the 24 h of burn injury, while the
      granulocyte percentage was increased. Leptin treatment, however, had no
      significant effect on burn-induced reversal of white blood cell ratios. On the
      other hand, burn-induced increase in the death of mononuclear cells and
      granulocytes was significantly reduced in leptin-treated rats. The results of the
      present study suggest that leptin may provide a therapeutic benefit in
      diminishing burn-induced inflammation and associated multiple organ failure.

PMID- 15582725
TI  - The effect of agouti-related protein on growth hormone secretion in adult male
      rats.
AB  - Agouti-related protein (AGRP) and neuropeptide Y (NPY) are synthesized in the
      same neurons in the hypothalamic arcuate nucleus. We have previously shown that
      NPY/AGRP neurons contain growth hormone (GH) receptor mRNA, and are activated
      following systemic GH administration. We also reported that NPY inhibits GH
      secretion when administered centrally. In this study, we have examined the effect
      of AGRP on GH secretion. Central administration of AGRP (83-132) as a single
      injection of 1 or 10 microg/rat, or chronic treatment of 1 microg/rat, every 12 h
      for 7 days, did not alter the GH secretory pattern of adult male rats. AGRP (83
      132) at doses of 1-100 nM (4 h) did not alter baseline- and GHRH-induced GH
      secretion from the rat pituitary cell cultures. These results suggest that AGRP
      does not play a significant role in the feedback regulation of the GH secretion.

PMID- 15582726
TI  - Augmentation of cocaine hyperactivity in rats by systemic ghrelin.
AB  - The feeding-relevant pathway by which food deprivation (FD) augments cocaine
      action is unknown. Systemic administration of the 28 amino acid acylated peptide
      ghrelin (1-10 nmol) increases food intake in rats and circulating levels of rat
      ghrelin are up-regulated by FD. The present experiment examined the impact of
      ghrelin or vehicle pretreatment on the locomotion and stereotypy induced by
      systemic cocaine hydrochloride. Male Sprague-Dawley rats were pretreated at -60
      min with 0 or 5 nmol rat ghrelin (IP) and then injected (IP) at time 0 with 0,
      2.5, 5.0, or 10.0 mg/kg cocaine. Locomotor activity was monitored over a 45-min
      post-cocaine period. Rats received the same ghrelin dose, but a different cocaine
      dose (in random order) on each of the four drug trials, with each drug trial
      separated by at least 2 days. Administration of 5 nmol ghrelin-0 mg/kg cocaine
      slightly increased locomotion relative to that of 0 nmol ghrelin-0 mg/kg cocaine.
      Cocaine increased locomotion as a function of dose in the 0 nmol ghrelin group,
      but the effect of cocaine was even greater when preceded by 5 nmol ghrelin. These
      results indicate that acute injection of ghrelin, at a feeding-relevant dose,
      augments the acute effects of cocaine on locomotion in rats.

PMID- 15582727
TI  - Hypotensive effect of novel chimeric peptides of met-enkephalin and FMRFa.
AB  - Endogenous opioid peptides like endomorphins, met-enkephalin and NPFF/FMRFamide
      family of neuropeptides, besides playing a role in modulation of antinociception,
      also affect cardiovascular system. Based on MERF, which consists of overlapping
      sequences of FMRFa and met-enkephalin, two chimeric peptides YGGFMKKKFMRFamide
      (YFa) and [D-Ala2] YAGFMKKKFMRFamide ([D-Ala2] YFa) were designed and
      synthesized. In this study, effect of YFa and [D-Ala2] YFa on arterial blood
      pressure and heart rate was evaluated in anaesthetized rats. Both YFa and [D
      Ala2] YFa showed a dose-dependent fall in mean arterial pressure in dose-range of
      13-78 micromol/kg. After naloxone treatment (5 mg/kg), vasodepressor effect of [D
      Ala2] YFa and YFa was only partially blocked as compared to met-enkephalin.
      Partial blockade of vasodepressive effect of YFa and [D-Ala2] YFa by naloxone may
      be attributed to interaction of these chimeric peptides with receptors other than
      naloxone-sensitive receptors such as anti-opioid receptors, adrenergic receptors
      and D-analogue receptors.

PMID- 15582728
TI  - Differential expression of Y receptors and signaling pathways in intestinal
      circular and longitudinal smooth muscle.
AB  - The expression and mechanisms of action of Y receptors were examined in dispersed
      intestinal smooth muscle cells of the rabbit. The mixed Y1/Y2 agonists, NPY and
      PYY, and the Y2 agonist, NPY13-36, elicited concentration-dependent contraction
      of circular muscle cells that was inhibited by the selective Y2 antagonist, BIIE
      0246. The Y4 agonist, PP, elicited similar, though weaker, contraction that was
      insensitive to Y1 and Y2 antagonists. The Y1 agonist, [Leu31, Pro34]NPY, did not
      elicit contraction of circular muscle cells. All Y receptor agonists inhibited
      cAMP formation in a PTx-sensitive fashion. In contrast, none of the agonists
      caused contraction of longitudinal muscle cells, and only the mixed Y1/Y2
      agonists, NPY and PYY, and the Y1 agonist, [Leu31, Pro34]NPY, inhibited cAMP
      formation and VIP-induced muscle cell relaxation. 125I-PYY binding in
      longitudinal muscle cells was inhibited by NPY, PYY, [Leu31, Pro34]NPY and the Y1
      antagonist, BIBP 3226. Contraction of circular but not longitudinal muscle cells
      by Y2 and Y4 agonists was observed also in cells isolated from human jejunum. The
      results indicate that Y2 and Y4 receptors are present only in intestinal circular
      muscle cells where they mediate contraction that is insensitive to PTx or Ca2+
      channel blockers. Y1 receptors, negatively coupled to adenylyl cyclase, are
      present in cells from both layers.

PMID- 15582729
TI  - Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium
      independent mechanism.
AB  - A lot of interest has engendered in glucagon-like peptide-1 (GLP-1) as an
      emerging new drug in the treatment of type 2 diabetes. GLP-1 exerts several
      effects that reduce glycemia in type 2 diabetes patients. We recently also
      demonstrated that GLP-1 ameliorates endothelial dysfunction in type 2 diabetes
      mellitus patients with established coronary heart disease, suggesting a new
      important cardioprotective role for GLP-1. Because hypertension is
      overrepresented in diabetes and is adversely influencing survival, we have now
      investigated direct GLP-1 effects on vascular beds in a rat organ bath model. It
      was found that GLP-1 relaxed femoral artery rings in a dose-response manner. The
      relaxant effect from GLP-1 was completely inhibited by the specific GLP-1
      receptor antagonist, exendin(9-39). Neither the specific nitric oxide (NO)
      synthase inhibitor, N-nitro-L-arginine, nor removing of endothelium, affected the
      GLP-1 relaxant effect. In conclusion, we now report a direct vascular action of
      GLP-1, relaxing conduit vessels independently of NO and the endothelium.

PMID- 15582730
TI  - Inhibition of phospholipase C-independent exocytotic responses in rat peritoneal
      mast cells by U73122.
AB  - The aminosteroid U73122 has been established as potent, selective, and cell
      permeable inhibitor C-type phosphatidylinositol-specific phospholipases (PI
      PLCs), and has been used to define a contribution of PI-PLCs as part of
      exocytotic signalling pathways in rat peritoneal mast cells (RPMCs). However,
      doubts have been raised regarding its PI-PLC selectivity of action. Therefore, in
      the present study, U73122 was tested in RPMCs under experimental conditions
      allowing to elicit exocytosis PI-PLC independently (streptolysin O [SLO]
      permeabilised cells; stimulated by GTPgammaS; in the presence of low
      concentrations of free Ca2+). The release of [3H]5-hydroxytryptamine ([3H]5-HT)
      from [3H]5-HT-loaded RPMCs served as measure of secretion. U73122 potently
      inhibited the exocytotic response induced by 10 microM GTPgammaS (Ca2+: 10(-6) M)
      in permeabilised cells (IC50: 0.6 microM, n=5) in an insurmountable manner. In
      intact RPMCs, with a nearly equal potency (IC50: 4 microM, n=4), U73122 also
      inhibited the PI-PLC-dependent exocytotic response induced by concomitant
      application of nerve growth factor and lyso-phosphatidylserine (NGF/lyso-PS).
      CONCLUSION: U73122 exerts potent PI-PLC-independent secretostatic effects,
      limiting its use to define PI-PLC function within exocytotic processes.

PMID- 15582731
TI  - Effects of vasoactive intestinal peptide and galanin on survival of cultured
      porcine myenteric neurons.
AB  - Enteric neuronal plasticity is probably fundamental in order to withstand injury
      or changes in intestinal activity. The role of the neuropeptides in
      neuroprotection is still enigmatic. The expression of galanin and vasoactive
      intestinal peptide (VIP) and the effects of the two peptides on survival of small
      intestinal porcine myenteric neurons cultured for 6 days were studied.
      Immunocytochemistry and cell counting were used to evaluate the numbers of
      surviving neurons and their expression of galanin and VIP. To reflect the in vivo
      situation, cryostat sections of porcine mid-jejunum were used. A concentration
      dependent and marked increase in neuronal survival was noted when neurons were
      grown in the presence of VIP (10(-8)-10(-6) M), whereas addition of galanin (10(
      8)-10(-6) M) slightly decreased neuronal survival. A dramatic increase in the
      proportions of myenteric neurons containing VIP or galanin immunoreactivity
      occurred during culturing. The presence of VIP further increased the number of
      galanin-expressing neurons. A majority of the galanin-immunoreactive neurons
      lacked VIP, while all VIP-immunoreactive neurons contained galanin. In
      conclusion, culturing porcine myenteric neurons in the presence of VIP increases,
      while the presence of galanin reduces, survival. Culturing significantly
      increased the proportion of neurons expressing VIP and/or galanin; the presence
      of VIP further increased the number of galanin-expressing neurons.

PMID- 15582732
TI  - A panel of 13 region-specific radioimmunoassays for measurements of human
      chromogranin B.
AB  - INTRODUCTION: The primary structure of human chromogranin B (CgB) contains 15
      pairs of basic amino acids, which are potential cleavage sites for specific
      endogenous proteases, but also other sites in the molecule can be subjected to
      cleavage. Several CgB-related peptides have been identified in tissue extracts.
      MATERIALS AND METHODS: Peptides homologous to defined parts of the human CgB
      molecule were selected and synthesized. Antibodies were raised and 13 specific
      radioimmunoassays were developed. Plasma samples from 19 patients with
      neuroendocrine tumors were collected and measured in all assays. RESULTS: All
      region-specific assays measured circulating levels of CgB-related peptides. Only
      five of the assays measured high concentrations of circulating CgB and two of
      them correlated with that of intact chromogranin A (CgA). CONCLUSION: The assays
      presented allow measurements of defined regions of CgB and will thus become
      important tools for further studies of the processing of CgB. One of the assays
      merit further investigations as a new marker for neuroendocrine tumors.

PMID- 15582733
TI  - Inhibitory effect of ghrelin on food intake is mediated by the corticotropin
      releasing factor system in neonatal chicks.
AB  - It is known that, in rats, central and peripheral ghrelin increases food intake
      mainly through activation of neuropeptide Y (NPY) neurons. In contrast,
      intracerebroventricular (ICV) injection of ghrelin inhibits food intake in
      neonatal chicks. We examined the mechanism governing this inhibitory effect in
      chicks. The ICV injection of ghrelin or corticotropin-releasing factor (CRF),
      which also inhibits feeding and causes hyperactivity in chicks. Thus, we examined
      the interaction of ghrelin with CRF and the hypothalamo-pituitary-adrenal (HPA)
      axis. The ICV injection of ghrelin increased plasma corticosterone levels in a
      dose-dependent or a time-dependent manner. Co-injection of a CRF receptor
      antagonist, astressin, attenuated ghrelin-induced plasma corticosterone increase
      and anorexia. In addition, we also investigated the effect of ghrelin on NPY
      induced food intake and on expression of hypothalamic NPY mRNA. Co-injection of
      ghrelin with NPY inhibited NPY-induced increase in food intake, and the ICV
      injection of ghrelin did not change NPY mRNA expression. These results indicate
      that central ghrelin does not interact with NPY as seen in rodents, but instead
      inhibits food intake by interacting with the endogenous CRF and its receptor.

PMID- 15582734
TI  - Antibacterial activity of N-alkylated disaccharide chitosan derivatives.
AB  - Antibacterial activity of the water-soluble N-alkylated disaccharide chitosan
      derivatives against Escherichia coli and Staphylococcus aureus was investigated.
      It was found that the antibacterial activity of chitosan derivatives was affected
      by the degree of substitution (DS) with disaccharide and the kind of disaccharide
      present in the molecule. Regardless the kind of disaccharide linked to the
      chitosan molecule, a DS of 30-40%, in general, exhibited the most pronounced
      antibacterial activity against both test organisms. E. coli and S. aureus were
      most susceptible to cellobiose chitosan derivative DS 30-40% and maltose chitosan
      derivative DS 30-40%, respectively, among the various chitosan derivatives
      examined. Although the disaccharide chitosan derivatives showed less
      antibacterial activity than the native chitosan at pH 6.0, the derivatives
      exhibited a higher activity than native chitosan at pH 7.0. Antibacterial
      activity of the chitosan derivatives (DS 30-40%) against E. coli increased as the
      pH increased from 5.0 and reached a maximum around the pH of 7.0-7.5. The effect
      of pH on the antibacterial activity of chitosan derivatives against S. aureus was
      not as pronounced as that observed with E. coli. Population reduction of E. coli
      or S. aureus in nutrient broth increased markedly upon increasing the
      concentration of chitosan derivatives from 0 to 500 ppm. No marked increase in
      population reduction was noted with further increase in the concentration of
      chitosan derivatives even up to 2000 ppm.

PMID- 15582735
TI  - Use of an electronic tongue and HPLC with electrochemical detection to
      differentiate molds in culture media.
AB  - A study was conducted to further evaluate an electronic tongue, using high
      performance liquid chromatography (HPLC) with electrochemical (EC) and UV
      detection as a reference method. The electronic tongue consisted of four working
      electrodes made of different metals and arranged in a standard three-electrode
      configuration. Pulses of voltage were applied to the metals, and the current
      responses were sampled and collected in a data matrix. The objectives of the
      present investigation were to examine the ability of the electronic tongue to
      distinguish between two mold species growing in three different media, and to
      obtain support for the hypothesis that the device actually discriminates between
      different redox-active metabolites produced by the molds. Peak areas in EC and UV
      HPLC chromatograms were collected in a data matrix. The electronic tongue data
      and the EC and UV data were then subjected to principal component analysis (PCA).
      A number of peaks in the HPLC-EC chromatograms indicated that the growth media
      contained redox-active metabolites. Moreover, PCA of peak areas in EC
      chromatograms revealed differences between the distribution of redox-active
      metabolites produced by the two species and between the three culture media. The
      same pattern was apparent in a PCA score plot of electronic tongue data. The
      peaks in the UV and EC chromatograms differed, and these were also shown by the
      PCA score plots.

PMID- 15582736
TI  - Sequencing of an internal transcribed spacer region of 16S-23S rRNA gene and
      designing of PCR primers for the detection of Salmonella spp. in food.
AB  - DNA sequences of an internal transcribed spacer (ITS) region for 40 Salmonella
      serovars were determined and compared with ITS sequences of Salmonella spp., and
      non-Salmonella spp. already available on the GenBank database. From such
      comparison, two Salmonella-specific ITS based PCR primers, ITSF and ITSR, were
      designed. When Salmonella strains with various serotypes were PCR assayed with
      primers ITSF/ITSR, all generated PCR products with molecular weight bands equal
      to 312 bp. On the other hand, 48 non-Salmonella isolates, including strains of
      Enterobacteriaceae and other food pathogens generated negative results. Detection
      limits of this PCR method was 1-9 CFU per assay. These PCR primers were used for
      the detection of Salmonella cells in artificially contaminated foods, including
      chicken meat and whole milk. The detection limit was 1-9 x 10(3) CFU per assay.
      With an 8-h enrichment step performed prior to the PCR assay, however, the
      detection limit became 1-9 CFU per gram of the food sample.

PMID- 15582737
TI  - Enterococcus species dominating in fresh modified-atmosphere-packaged, marinated
      broiler legs are overgrown by Carnobacterium and Lactobacillus species during
      storage at 6 degrees C.
AB  - In order to show which of the initial lactic acid bacteria (LAB) contaminants are
      also causing spoilage of a modified-atmosphere-packaged (MAP), marinated broiler
      leg product at 6 degrees C, LAB were enumerated and identified on the 2nd and
      17th days following manufacture. A total of 8 fresh and 13 spoiled packages were
      studied for LAB levels. In addition, aerobic mesophilic bacteria and
      Enterobacteriaceae were determined. The average CFU/g values in the 8 fresh
      packages were 1.3 x 10(3), 9.8 x 10(3) and 2.6 x 10(2) on de Man Rogosa Sharpe
      agar (MRS), Plate Count Agar (PCA) and Violet Red Bile Glucose agar (VRBG),
      respectively. The commercial shelf life for the product had been set as 12 days,
      and all packages analyzed on the 17th day were deemed unfit for human consumption
      by sensory analysis. The corresponding CFU/g averages in the spoiled product were
      1.4 x 10(9), 1.1 x 10(9) and 3.9 x 10(7) on MRS, PCA and VRBG agar, respectively.
      For characterization of LAB population, 104 colonies originating from the fresh
      packages and 144 colonies from the spoiled packages were randomly picked,
      cultured pure and identified to species level using a 16 and 23S rDNA HindIII
      RFLP (ribotyping) database. The results showed that enterococci (35.7% of the LAB
      population) were dominating in the fresh product, whereas carnobacteria (59.7%)
      dominated among the spoilage LAB. Enterococcus faecalis, Carnobacterium piscicola
      and Carnobacterium divergens were the main species detected. In general, when the
      initial LAB population is compared to the spoilage LAB, a shift from
      homofermentative cocci towards carnobacteria, Lactobacillus sakei/curvatus and
      heterofermentative rods is seen in this marinated product.

PMID- 15582738
TI  - Ecology and characterization by molecular methods of Staphylococcus species
      isolated from fresh sausages.
AB  - Staphylococcus spp. ecology in fresh sausages stored at 4 degrees C for a period
      of 10 days was investigated. Microbiological analyses to assess the quality and
      safety of the products studied were carried out, and strains on MSA agar were
      isolated. A total of 85 strains were identified, by traditional methods, as
      Staphylococcus spp. and a PCR-DGGE method, together with a S. xylosus-specific
      PCR, were used to determine the species of the strains isolated. Almost 50% of
      them were recognized as S. xylosus, but strains of S. pasteuri, S. warneri, S.
      equorum and S. succinus, were also found. Interesting population dynamics were
      observed, characterized by a succession of S. pasteuri and S. warneri at 0 day,
      with S. xylosus at 3 days and S. equorum at 6 and 10 days. Molecular
      characterization of S. xylosus strains and cluster analysis highlighted the
      presence of six main populations in the fresh sausages studied. However, the
      clusters were formed by strains isolated at different days of storage, implying a
      homogeneous distribution of the six subpopulations throughout the period in the
      products followed.

PMID- 15582739
TI  - Characterization and identification of lactic acid bacteria in "morcilla de
      Burgos".
AB  - A total of 176 lactic acid bacteria (LAB) isolated from a typical Spanish blood
      sausage called "morcilla de Burgos" were identified by means of phenotypic
      characteristics and 16S rDNA RFLP (ribotyping). LAB were isolated from "morcilla"
      of different producers and in different storage periods, which includes
      unpackaged, vacuum and modified atmosphere packaged "morcilla" and vacuum packed
      and pasteurised "morcilla". The knowledge of specific spoilage bacteria of
      "morcilla de Burgos" will be useful to design new preservation methods to extend
      the shelf-life of this product. Identification made according to phenotypic and
      biochemical characteristics shows the majority of the isolates were
      heterofermentative LAB (93.2%) and eight different bacterial groups could be
      distinguished (A-G). Weisella viridescens was the main species detected (42%). In
      addition, Leuconostoc spp. (23.9%), Weissella confusa (11.4%) and Lactobacillus
      fructosus (5.7%) species were found. Few strains were phenotypically
      misidentified as Lactobacillus sanfrancisco, Pediococcus spp., Lactobacillus
      sakei/curvatus and Carnobacterium spp. and 11 strains remained unknown. Most of
      the leuconostocs were identified as Leuconostoc mesenteroides and Leuconostoc
      carnosum species. Ribotyping shows a quite good correlation with phenotypic
      methods, although it has been possible to identify 15 different clusters. W.
      viridescens and leuconostocs were also the predominant LAB. Strains identified as
      W. confusa by phenotypic characteristics were resolved in W. confusa and
      Weissella cibaria by ribotyping. Neither Carnobacterium piscicola nor Lb.
      sanfrancisco were identified by means of genotypic method. All Lb. fructosus
      strains and some more included in different phenotypic groups (17 strains in
      total) could not be associated with any reference strain (cluster VII).

PMID- 15582740
TI  - Antimicrobial resistance in Salmonella enteritidis strains isolated from broiler
      carcasses, food, human and poultry-related samples.
AB  - Antimicrobial resistance was investigated in 91 Salmonella enteritidis isolates
      from broiler carcasses, food, human and poultry-related samples originated from
      South of Brazil. A great proportion of resistant strains was found, 90.1% showing
      resistance to at least one antimicrobial drug. There was a high resistance to
      sulfonamides (75.8%) and nitrofurantoin (52.8%). Lower levels of resistance were
      found for tetracycline (15.4%), streptomycin (7.7%), nalidixic acid (7.7%),
      gentamicin (5.5%), norfloxacin (3.3%), trimethoprim (3.3%), cefalotin (2.2%),
      ampicillin (1.1%), and chloramphenicol (1.1%). Resistance to ciprofloxacin was
      not detected. A total of 51.6% of S. enteritidis strains were multiresistant
      (resistance to two or more antimicrobial agents) and 18 resistance patterns were
      found. The highest resistance was found in strains isolated from poultry-related
      samples, where all strains were resistant to at least one antimicrobial agent. No
      predominant resistance pattern was related to phage type in our isolates. The
      high number of antimicrobial resistant S. enteritidis found in Southern Brazil
      indicates the need for the prudent drugs uses to diminish the development and
      spread of antimicrobial resistance.

PMID- 15582741
TI  - Water activity affects heat resistance of microorganisms in food powders.
AB  - To study the factors and mechanisms involved in microorganisms' death or
      resistance to temperature in low-water-activity environments, a previous work
      dealt with the viability of dried microorganisms immobilized in thin-layer on
      glass beads. This work is intended to check the efficiency of a rapid heating
      cooling treatment to destroy microorganisms that were dried after mixing with
      wheat flour or skim milk. The thermoresistance of the yeast Saccharomyces
      cerevisiae and the bacterium Lactobacillus plantarum were studied. Heat stress
      was applied at two temperatures (150 or 200 degrees C) for treatments of one of
      four durations (5, 10, 20, or 30 s) and at seven levels of initial water activity
      (a(w)) in the range 0.10 to 0.70. This new treatment achieved a microbial
      destruction of eight log reductions. A specific initial water activity was
      defined for each strain at which it was most resistant to heat treatments. On
      wheat flour, this initial a(w) value was in the range 0.30-0.50, with maximal
      viability value at a(w)=0.35 for L. plantarum, whatever the temperature studied,
      and 0.40 for S. cerevisiae. For skim milk, a variation in microbial viability was
      observed, with optimal resistance in the range 0.30-0.50 for S. cerevisiae and
      0.20-0.50 for L. plantarum, with minimal destruction at a(w)=0.30 whatever the
      heating temperature is.

PMID- 15582742
TI  - Survey of Fusarium toxins in foodstuffs of plant origin marketed in Germany.
AB  - A total of 219 samples of foodstuffs of plant origin, consisting of grain-based
      food, pseudocereals and gluten-free food as well as vegetables, fruits, oilseeds
      and nuts, were randomly collected during 2000 and 2001 in food and health food
      stores. A spectra of 13 trichothecene toxins including diacetoxyscirpenol (DAS),
      15-monoacetoxyscirpenol (MAS), scirpentriol (SCIRP), T-2 and HT-2 toxins (T-2, HT
      2), T-2 triol, T-2 tetraol, neosolaniol (NEO) of the A-type as well as
      deoxynivalenol (DON), 3- and 15-acetyl-DON (3-, 15-ADON), nivalenol (NIV), and
      fusarenon-X (FUS-X) of the B-type were determined by gas chromatography/mass
      spectrometry. Analysis of zearalenone (ZEA), alpha- and beta-zearalenol (alpha-
      and beta-ZOL) was made by high-performance liquid chromatography with
      fluorescence and UV-detection. Detection limits ranged between 1 and 19
      microg/kg. Out of 84 samples of cereal-based including gluten-free foods, 60
      samples were positive for at least one of the toxins DON, 15-ADON, 3-ADON, NIV, T
      2, HT-2, T-2 tetraol and ZEA, with incidences at 57%, 13%, 1%, 10%, 12%, 37%, 4%
      and 38%, respectively, whereas SCIRP and its derivatives MAS and DAS, T-2 triol,
      Fus-X as well as alpha- and beta-ZOL were not detected in any sample of this
      subgroup. Contents of DON ranged between 8 and 389 microg/kg, for all other
      toxins determined concentrations were below 100 microg/kg. The pseudocereals
      amaranth, quinoa and buckwheat were free of the toxins investigated. Ten of 85
      samples of vegetables and fruits were toxin positive. ZEA and the type A
      trichothecenes MAS, SCIRP, DAS, HT-2 were detected in 7, 3, 2, 1 and 1 samples,
      respectively. Out of 35 samples of oilseeds and nuts, 7 samples were toxin
      positive. HT-2, T-2 and ZEA were detected in 4, 3 and 4 samples, respectively. In
      vegetables and fruits as well as in oilseeds and nuts, toxin levels were below 50
      microg/kg. None of the B-type trichothecenes analysed was found for both
      subgroups.

PMID- 15582743
TI  - Metabiotic associations of molds and Salmonella Poona on intact and wounded
      cantaloupe rind.
AB  - Salmonella Poona, a serotype rarely implicated in human infections, has recently
      caused several cantaloupe-associated outbreaks of salmonellosis. Metabiotic
      associations of molds and foodborne pathogens on produce have been reported. We
      tested proteolytic activity and measured changes in the pH of cantaloupe rind
      caused by growth of Alternaria alternata, Cladosporium cladosporioides, Epicoccum
      nigrum, Geotrichum candidum, and Penicillium expansum. Survival and growth
      characteristics of Salmonella Poona co-infected with each mold on the surface
      rind and in wounded rind tissue as affected by temperature were determined. C.
      cladosporioides, G. candidum, and P. expansum, but not A. alternata and E.
      nigrum, showed proteolytic activity on agar media containing gelatin and/or
      casein, with concurrent increases in pH, thus favoring survival and growth of
      salmonellae. Intact and mechanically wounded tissue of cantaloupe rinds were
      inoculated with a five-strain mixture of S. Poona and/or test mold. Five
      inoculation schemes were used: mold only, S. Poona only, mold and S. Poona
      simultaneously, mold then S. Poona 3 days later, and S. Poona then mold 3 days
      later. The pH of cantaloupe rinds inoculated with molds and stored at 20 degrees
      C for 14 days was significantly higher (P < or =0.05) than on day 0. Only the pH
      of rinds inoculated with C. cladosporioides or G. candidum was significantly
      higher (P < or =0.05) on day 21 than on day 0, when cantaloupes were stored at 4
      degrees C. An initial population of S. Poona increased from 3.3 log(10)
      cfu/sample (ca. 7 cm(2)) of cantaloupe rind to populations as high as 9.5 log(10)
      cfu/sample during storage at 20 degrees C for up 14 days, regardless of co
      inoculation with molds. Populations of S. Poona decreased or remained constant at
      4 degrees C for up to 21 days. Results demonstrate that persistence and growth of
      S. Poona on intact, wounded, and decaying cantaloupe rind are not markedly
      affected by the presence of molds.

PMID- 15582744
TI  - Molecular misreading: the frequency of dinucleotide deletions in neuronal mRNAs
      for beta-amyloid precursor protein and ubiquitin B.
AB  - Human neuronal cells contain mutant beta-amyloid precursor protein (APP) and
      ubiquitin B (UBB) mRNAs, in which dinucleotide deletions ('Delta') are generated
      in/around GAGAG-motifs by an unknown mechanism referred to as 'Molecular
      Misreading.' The encoded frameshifted (+1) proteins accumulate in the
      neuropathological hallmarks of Alzheimer's disease (AD) and in other
      neurodegenerative and age-related diseases. To measure the concentration of Delta
      mRNAs, we developed a highly sensitive and specific assay, utilizing peptide
      nucleic acid-mediated PCR clamping, followed by cloning and colony hybridization
      with sequence-specific oligonucleotide probes. We found only a few molecules of
      Delta mRNA/microg of cellular RNA, at levels <10(-5) to 10(-6) x the
      concentration of WT mRNA, in RNA extracted from: (i) cultured human neuroblastoma
      cells grown under a variety of conditions, (ii) the frontal half of brains from
      wild type and XPA(-/-) DNA repair-deficient mice, and (iii) post-mortem temporal
      cortices from humans. Importantly, in RNA from the temporal cortices of AD and
      Down Syndrome patients that contain betaAPP+1 and UBB+1 immunoreactive cells, we
      found the same low levels of Delta mRNA. We infer that the accumulation of +1
      proteins in neurons of these patients is not caused by an increase in the
      concentration of Delta mRNAs.

PMID- 15582745
TI  - Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of
      Aging.
AB  - OBJECTIVE: To investigate the association between use of calcium channel blockers
      (CCB), dihydropyridine (DHP) or nondihydropyridine (nonDHP) type CCB and risk of
      developing Alzheimer's Disease (AD) or mortality. There is evidence suggesting
      that calcium plays a key role in changes in the brain leading to AD. Previous
      reports suggest a possible role for CCB in the treatment of AD. However, there
      are some indications that CCB increase mortality in patients with cardiac
      disease. METHODS: Subjects were 1092 participants in the Baltimore Longitudinal
      Study of Aging (BLSA) older than 60 years of age. Data on CCB use was collected
      prospectively for up to 19 years. Cox proportional hazards regression was used to
      estimate relative risks (RR) and confidence intervals (CI) of AD and mortality
      associated with use of CCB or use of only DHP or nonDHP-CCB. Analyses were
      adjusted for gender, education, smoking, blood pressure and history of heart
      problems. RESULTS: Use of DHP-CCB was not associated with a significantly reduced
      risk of AD compared to non-users, although the estimate of the RR was low with
      DHP-CCB (RR = 0.30, 95% CI = 0.07-1.25, P = 0.10). Use of nonDHP-CCB was not
      associated with reduced risk of AD and the estimate of the RR risk was close to
      one (RR = 0.82, 95% CI = 0.37-1.83, P = 0.63). In addition, there was no increase
      in mortality among users of DHP-CCB (RR = 0.64, 95% CI = 0.32-1.29, P = 0.21) or
      nonDHP-CCB (RR = 1.10, 95% CI = 0.65-1.87, P = 0.72). CONCLUSION: Users of DHP
      CCB and nonDHP-CCB in this study did not have a significantly reduced risk of AD.

PMID- 15582746
TI  - Decreased EEG synchronization in Alzheimer's disease and mild cognitive
      impairment.
AB  - The hypothesis of a functional disconnection of neuro-cognitive networks in
      patients with mild cognitive impairment (MCI) and Alzheimer Dementia was
      investigated using baseline resting EEG data. EEG databases from New York (264
      subjects) and Stockholm (155 subjects), including healthy controls and patients
      with varying degrees of cognitive decline or Alzheimer Dementia were analyzed
      using Global Field Synchronization (GFS), a novel measure of global EEG
      synchronization. GFS reflects the global amount of phase-locked activity at a
      given frequency by a single number; it is independent of the recording reference
      and of implicit source models. Patients showed decreased GFS values in Alpha,
      Beta, and Gamma frequency bands, and increased GFS values in the Delta band,
      confirming the hypothesized disconnection syndrome. The results are discussed
      within the framework of current knowledge about the functional significance of
      the affected frequency bands.

PMID- 15582747
TI  - Diminished aromatase immunoreactivity in the hypothalamus, but not in the basal
      forebrain nuclei in Alzheimer's disease.
AB  - In previous studies we have shown in Alzheimer's disease (AD) an enhanced nuclear
      estrogen receptor (ER) alpha expression in the cholinergic basal forebrain
      nuclei, i.e. the vertical limb of the diagonal band of Broca (VDB) and the
      nucleus basalis of Meynert (NBM), and in a number of hypothalamic nuclei, i.e.
      the supraoptic nucleus (SON), the infundibular nucleus (INF), the medial
      mamillary nucleus (MMN). We aimed at determining whether the increase in nuclear
      ERalpha seen in AD patients was related to a rise in local production of
      estrogens by aromatase (P-450arom), which is a key enzyme that catalyzes the
      biosynthesis of estrogens from precursor aromatizable androgens. We confirmed for
      the first time the presence of aromatase mRNA in neurons and glial cells in the
      human NBM and the tuberomamillary nucleus by RT-QPCR using laser microdissection.
      Enhanced aromatase immunoreactivity (ir) was indeed observed in the NBM in AD.
      However, in contrast a decreased aromatase-ir was found in the SON, INF and MMN
      of AD patients. In addition, P-450arom-ir was clearly diminished in ependymal and
      choroid plexus cells in AD. While an increase in aromatase-ir was found in the
      NBM and SON during normal aging, a decrease in staining was observed in the MMN.
      No sex differences in young control, elderly control or AD patients were present
      in any of the nuclei studied. In conclusion, brain P-450arom-ir and the
      relationship of its regulation with plasma sex steroid levels, estrogen and
      androgen receptors in the human hypothalamus and basal forebrain are region
      specific.

PMID- 15582748
TI  - The apoE receptor apoER2 is involved in the maintenance of efficient synaptic
      plasticity.
AB  - ApoER2 is one of the major receptors for ApoE in the brain, and has been shown to
      be involved not only in lipoprotein endocytosis, as other members of the LDL
      receptor family of receptors, but also in various cellular functions such as
      signalling and cellular guidance. By using a model of synaptic plasticity in mice
      lacking none, one or two alleles of the apoER2 gene, we investigated the
      implication of such a receptor deficiency on the remodelling process. Our results
      indicate that animals lacking apoER2 express higher levels of brain APP, as well
      as both key amyloid peptides, while apoE levels are slightly lower. Following
      entorhinal cortex lesioning, apoE levels increase in the deafferented
      hippocampus, while a delay in the increase of APP was observed. Hippocampal
      amyloid levels are also increased in response to the lesion, and highly
      potentiated by the complete absence of apoER2 gene. The results suggest a
      significant role for apoER2 in signalling various proteins in response to massive
      deafferentation and may participate in maintaining efficient synaptic plasticity
      and dendritic remodelling.

PMID- 15582749
TI  - Quantitative proteomic analysis of age-related changes in human cerebrospinal
      fluid.
AB  - Identification of cerebrospinal fluid (CSF) biomarkers of the common age-related
      neurodegenerative diseases would be of great value to clinicians because of the
      difficulties in differential diagnoses of these diseases in clinical practice.
      Proteins are one class of potential biomarkers currently under investigation in
      the hope that different ensembles of proteins will aid in the diagnosis of these
      diseases, as well as in the assessment of progression and response to therapy.
      However, before undertaking a rational approach to CSF protein biomarkers of age
      related neurodegeneration, we must first systematically identify CSF proteins and
      determine whether their levels change with normal aging. In this study, we used a
      powerful shotgun proteomic method, two-dimensional microcapillary liquid
      chromatography electrospray ionization tandem mass spectrometry, to identify
      proteins in human CSF. Additionally, using pooled CSF samples, we quantitatively
      compared the CSF proteome of younger adults with that of older adults using
      isotope-coded affinity tags (ICAT). From these studies we identified more than
      300 proteins in CSF and found that there were 30 proteins with >20% change in
      concentrations between older and younger individuals. Finally, we validated
      changes in concentration for two of these proteins using Western blots in CSF
      from a separate set of individuals. These data not only expand substantially our
      current knowledge regarding human CSF proteins, but also supply the necessary
      information to appropriately interpret protein biomarkers of age-related
      neurodegenerative diseases.

PMID- 15582750
TI  - Estrogen use and brain metabolic change in postmenopausal women.
AB  - OBJECTIVE: We used positron emission tomography to evaluate cerebral glucose
      metabolic change in postmenopausal women in a naturalistic observational study.
      METHOD: Women estrogen users (n = 11) and non-users (n = 9) were studied at
      baseline and 2 years later. Analyses focused on glucose metabolism in regions
      previously reported to decline in older persons at risk for Alzheimer's disease
      (AD) (posterior cingulate and lateral temporal cortex). RESULTS: Region of
      interest (ROI) analysis at baseline showed no regional differences between women
      estrogen users and non users. ROI follow-up analysis revealed that women non
      users declined significantly in the posterior cingulate cortex (P= 0.04).
      Statistical parametric mapping (SPM) analysis confirmed a significant decrease in
      metabolism of the posterior cingulate cortex among non-users at 2-year follow-up
      (P = 0.004). In contrast, women estrogen users did not exhibit significant
      metabolic change in the posterior cingulate. CONCLUSIONS: Estrogen use may
      preserve regional cerebral metabolism and protect against metabolic decline in
      postmenopausal women, especially in posterior cingulate cortex, the region of the
      brain found to decline in the earliest stages of AD.

PMID- 15582751
TI  - Brain activation during encoding and recognition of verbal and figural
      information in older adults.
AB  - Positron emission tomography (PET) patterns of cerebral blood flow associated
      with verbal and figural memory are described in relation to their value as
      functional probes for studying longitudinal changes that occur in the aging
      brain. Relative to a matching control task, verbal and figural encoding increase
      blood flow in prefrontal cortex (PFC), anterior cingulate, insular, lateral and
      medial temporal, occipital cortex and the cerebellum. Additionally, medial
      temporal regions exhibited greater activity during figural encoding relative to
      verbal encoding. During recognition, blood flow increases in prefrontal,
      cingulate, insular, and lateral temporal and Broca's areas. Analysis of
      hemispheric asymmetry reveals that the prefrontal cortex exhibits regionally
      dependent results. Prefrontal region BA 10 demonstrates more bilateral activation
      during encoding and retrieval, whereas BA 46 shows right greater than left
      activation during both encoding and retrieval. Overall, the two tasks activate
      diverse regions within the frontal, temporal and occipital lobes of the brain,
      including areas that show age-related structural changes, proving their
      usefulness in the longitudinal assessment of brain function in the elderly.

PMID- 15582752
TI  - Contribution of the MTHFR gene to the causal pathway for depression, anxiety and
      cognitive impairment in later life.
AB  - Homocysteine (Hcy) is harmful to neurons and blood vessels, including the
      cerebral microvasculature. It is possible that such effects contribute to the
      cascade of events that leads to cognitive decline, dementia, and depression in
      later life. Hcy is produced during the metabolism of the essential amino-acid
      methionine, which also involves a methyl group transfer derived from folate and
      choline metabolism. Its plasma level can be influenced by factors such as age,
      vitamin deficiency, renal function, and a common mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene, where cytosine is replaced by
      thymidine (C-->T) at nucleotide position 677. Subjects with the TT genotype have
      higher homocysteine levels and may be particularly prone to experiencing
      depression as a result of high plasma Hcy and dysfunction of methylation
      metabolic pathways critical to the synthesis of noradrenaline and serotonin. We
      designed the present study to investigate whether older women with the TT
      genotype would have higher depression and lower cognitive scores than women with
      CT and CC genotypes. A total of 240 community-dwelling women aged 70 years or
      over volunteered to take part in the study - 29 carried the TT genotype, 113 the
      CT and 98 the CC genotype. The Beck Depression Inventory (BDI) score for subjects
      with the TT genotype was statistically similar to the other groups (P = 0.609).
      Plasma Hcy showed a modest and significant correlation with BDI scores (r = 0.21)
      that was independent from age, B12 and folate levels. There was no association
      between beck anxiety inventory (BAI) scores and MTHFR genotype or homocysteine
      levels. The cognitive assessment of participants included measures of verbal
      memory, memory for faces, verbal fluency, visuo-spatial abilities and the
      cognitive section of the Cambridge Examination For Mental Disorders Of The
      Elderly (CAMCOG)-MTHFR genotype had no clear association with cognitive scores.
      These results indicate that, in isolation, the MTHFR C677T gene variation does
      not play an important role in the modulation of mood and cognitive performance in
      later life.

PMID- 15582753
TI  - The nitric oxide donor molsidomine antagonizes age-related memory deficits in the
      rat.
AB  - The effects of the nitric oxide (NO) donor molsidomine on aged rats' cognition
      were evaluated in two different behavioral tasks: the step-through passive
      avoidance paradigm and the object recognition test. Post-training injection of
      molsidomine (at 4 but not at 2 mg/kg) significantly counteracted the performance
      deficits displayed by old rats in both the behavioral paradigms. These results
      support and extend prior findings about the implication of NO in learning and
      memory mechanisms. In addition, for the first time, a NO donor was found to
      antagonize age-related memory impairments, suggesting that the integrity of the
      NO-ergic system may be important in brain aging processes.

PMID- 15582754
TI  - Sleep wake profile and EEG spectral power in young or old senescence accelerated
      mice.
AB  - Changes occurring with age in cortical EEG and sleep-wake states architecture
      were examined in senescence accelerated prone (SAMP8) or senescence resistant
      (SAMR1) mice (age: 2 and 12 months) under baseline conditions or after a 4 h
      sleep deprivation (SD). In baseline conditions, an increase in slow wave sleep
      (SWS) amount (21-24%) occurs at the expense of the wakefulness (W) in old SAMP8
      and SAMR1 mice versus young animals. In these conditions, SWS latency is reduced
      (67-72%). Moreover, in SAMP8 and SAMR1 mice, aging deteriorates paradoxical sleep
      (PS) architecture with more pronounced changes in SAMP8 (amount: -63%; episode
      duration: -44%; latency: +286%; circadian component loss; and EEG theta (theta)
      peak frequency (TPF): -1 Hz). During the 4 h recovery subsequent to a 4 h sleep
      deprivation, old SAMP8 mice exhibit an enhanced sensitivity resulting in SWS
      (+62%) and PS (+120%) rebounds, a characteristic of this inbred strain. Results
      obtained are discussed in line with the age-related learning and memory
      impairments existing in SAMP8 animals. In particular, the reduced cognitive
      performances described in old SAMP8 might be linked to the TPF deterioration
      during PS.

PMID- 15582755
TI  - Effect of aging on neuroglobin expression in rodent brain.
AB  - Neuroglobin (Ngb), a recently discovered O2-binding heme protein related to
      hemoglobin and myoglobin, protects neurons from hypoxic-ischemic injury in vitro
      and in vivo. In immunostained mouse brain sections, we found widespread
      expression of Ngb protein in neurons, but not astrocytes, of several brain
      regions that are prominently involved in age-related neurodegenerative disorders.
      Western blots from young adult (3 month), middle-aged (12 month), and aged (24
      month) rats showed an age-related decline in Ngb expression in cerebral
      neocortex, hippocampus, caudate-putamen, and cerebellum. Loss of this
      neuroprotective protein may have a role in increasing susceptibility to age
      related neurological disorders.

PMID- 15582757
TI  - Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and
      simplification of the Utstein templates for resuscitation registries. A statement
      for healthcare professionals from a task force of the international liaison
      committee on resuscitation (American Heart Association, European Resuscitation
      Council, Australian Resuscitation Council, New Zealand Resuscitation Council,
      Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation,
      Resuscitation Council of Southern Africa).
AB  - Outcome following cardiac arrest and cardiopulmonary resuscitation is dependent
      on critical interventions, particularly early defibrillation, effective chest
      compressions, and advanced life support. Utstein-style definitions and reporting
      templates have been used extensively in published studies of cardiac arrest,
      which has led to greater understanding of the elements of resuscitation practice
      and progress toward international consensus on science and resuscitation
      guidelines. Despite the development of Utstein templates to standardize research
      reports of cardiac arrest, international registries have yet to be developed. In
      April 2002 a task force of ILCOR met in Melbourne, Australia, to review worldwide
      experience with the Utstein definitions and reporting templates. The task force
      revised the core reporting template and definitions by consensus. Care was taken
      to build on previous definitions, changing data elements and operational
      definitions only on the basis of published data and experience derived from those
      registries that have used Utstein-style reporting. Attention was focused on
      decreasing the complexity of the existing templates and addressing logistical
      difficulties in collecting specific core and supplementary (i.e., essential and
      desirable) data elements recommended by previous Utstein consensus conference.
      Inconsistencies in terminology between in-hospital and out-of-hospital Utstein
      templates were also addressed. The task force produced a reporting tool for
      essential data that can be used for both quality improvement (registries) and
      research reports and that should be applicable to both adults and children. The
      revised and simplified template includes practical and succinct operational
      definitions. It is anticipated that the revised template will enable better and
      more accurate completion of all reports of cardiac arrest and resuscitation
      attempts. Problems with data definition, collection, linkage, confidentiality,
      management, and registry implementation are acknowledged and potential solutions
      offered. Uniform collection and tracking of registry data should enable better
      continuous quality improvement within every hospital, EMS system, and community.

PMID- 15582758
TI  - Karl Landsteiner, the discoverer of blood groups.

PMID- 15582759
TI  - International EMS systems: Greece.
AB  - Emergency Medical Services (EMS) in Greece have been created to offer first aid,
      primary medical treatment if required, stabilisation and safe and rapid transfer
      to the closest appropriate hospital. To achieve these objectives, organised
      systems have been established with trained personnel and physicians, suitable
      equipment, communication centres and protocols. We present the Greek EMS system
      and explain its history, structure, training, cooperation with Emergency
      Departments (ED) and an outlook on the future.

PMID- 15582760
TI  - Drowning: a review of epidemiology, pathophysiology, treatment and prevention.
AB  - Although often preventable, drowning remains a leading cause of accidental death,
      especially in children. New definitions classify drowning as the process of
      experiencing respiratory impairment from submersion or immersion in a liquid. The
      key pathophysiological feature in drowning is hypoxia. Accurate neurological
      prognosis cannot be predicted from the initial clinical presentation, laboratory,
      radiological, or electrophysiological examinations. Prompt and aggressive
      resuscitation attempts are crucial for optimal survival. This article reviews the
      epidemiology, pathophysiology, treatment, and prevention of drowning.

PMID- 15582761
TI  - Improved prediction of defibrillation success for out-of-hospital VF cardiac
      arrest using wavelet transform methods.
AB  - We report an improved method for the estimation of shock outcome prediction based
      on novel wavelet transform-based time-frequency methods. Wavelet-based peak
      frequency, energy, mean frequency, spectral flatness and a new entropy measure
      were studied to predict shock outcome. Of these, the entropy measure provided
      optimal results with 60 +/- 6% specificity at 91 +/- 2% sensitivity achieved for
      the prediction of return of spontaneous circulation (ROSC). These results
      represent a major improvement in shock prediction in human ventricular
      fibrillation.

PMID- 15582762
TI  - Vasopressin administered with epinephrine is associated with a return of a pulse
      in out-of-hospital cardiac arrest.
AB  - OBJECTIVE: Recent data suggest that using vasopressin in combination with
      epinephrine (adrenaline) may improve treatment of out-of-hospital cardiac arrest.
      This study examined local experience with the combination of epinephrine and
      vasopressin administration. METHODS: Data were obtained from an urban, municipal
      emergency medical service that does not include vasopressin in its formulary. A
      physician is dispatched to the scene of all cardiac arrest patients treated by
      this system. Vasopressin could be administered in addition to epinephrine to
      subjects with out-of-hospital cardiac arrest by the on-scene physician.
      Demographic information, drug administration and return of pulses were abstracted
      from patient care records for a 1-year interval. Multivariate logistic regression
      was used to assess the relationship between vasopressin use and outcomes.
      RESULTS: During the study period, data were available for 298 subjects receiving
      epinephrine-only (n=231, 78%), a combination of 40 IU vasopressin and epinephrine
      (n=37, 12%) or no vasopressor drugs (n=30, 10%). Among patients receiving
      vasopressor drugs, pulse was restored for 74 subjects (28%), and 56 subjects
      (21%) had a pulse on arrival at the hospital. Return of pulses was associated
      with witnessed collapse, bystander CPR, and an initial ECG rhythm of ventricular
      fibrillation or tachycardia. Subjects receiving vasopressin and epinephrine were
      more likely to have a return of pulses during the resuscitation (LR: 2.73; 95%
      CI: 1.24, 6.03) and at hospital arrival (3.85; 1.71, 8.65) than subjects treated
      with epinephrine alone. CONCLUSIONS: There is an association between using
      vasopressin in combination with epinephrine and restoration of circulation after
      out-of-hospital cardiac arrest.

PMID- 15582763
TI  - External defibrillation in the left lateral position--a comparison of manual
      paddles with self-adhesive pads.
AB  - INTRODUCTION: Firm paddle force during defibrillation lowers transthoracic
      impedance (TTI) and increases transmyocardial current, increasing the chances of
      successful cardioversion. Current protocols recommend that if defibrillation
      using the anterior-apical (AA) paddle position fails, the anterior-posterior (AP)
      position should be used. This generally requires the patient to be placed in the
      left lateral position with the operator leaning over the patient. Avoiding
      physical contact with the patient during defibrillation subjectively makes
      application of firm paddle force difficult in the AP position. We compared TTI
      between the AA and AP positions and between manual paddles and self-adhesive pads
      to establish if the AP position precludes firm paddle force and to compare TTI
      between paddles and self-adhesive pads. METHODS: Twenty-one consecutive patients
      undergoing elective cardioversion (age 39-82) were studied. TTI was measured
      between pairs of manually held paddles and self-adhesive pads using AA placement
      with the patient supine, and AP placement with the patient left lateral position.
      RESULTS: Mean TTI using the AP electrode position was lower using manual paddles
      (66.5 Omega; 95% CI 60.2-72.9 Omega) than that using self-adhesive pads (92.1
      Omega; 95% CI 81.5-102.7 Omega; 95% CI between the mean =15.8-35.5 Omega; P
      <0.0001). TTI was significantly less using the manual paddles compared with self
      adhesive pads in both AA and AP positions (P <0.0001). CONCLUSION: Despite the
      subjective difficulties of defibrillating patients in the AP position whilst
      leaning over them, use of manual paddles achieves a lower TTI than that achieved
      with self-adhesive pads.

PMID- 15582764
TI  - Outcome of out-of-hospital cardiac arrest--why do physicians withhold
      resuscitation attempts?
AB  - OBJECTIVE: To describe the outcome of out-of-hospital cardiac arrest (OHCA) with
      a focus on why physicians withhold resuscitation attempts. METHODS: Prospective
      collection of data during 12 months by the anaesthesiologists from the Advanced
      Life Support unit (ALS) of the Emergency Medical Service (EMS) according to the
      Utstein template. RESULTS: In total, 499 OHCA were analysed and 266 patients
      received cardiopulmonary resuscitation (CPR) by the ALS unit. Initial rhythm was
      ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT) in 35%,
      asystole in 38%, and other rhythm in 27%. Of the 266 treated patients, 83 (31%)
      patients had a spontaneous circulation on admission to hospital. Survival to
      discharge from hospital was 6.2% for all cases of OHCA, 11.7% for all 266 treated
      patients, and 20.5% for patients with witnessed cardiac arrest and presumed
      cardiac aetiology in VF. On arrival, the physician decided in 233 cases to
      withhold or discontinue CPR. The explanation for this was prolonged anoxia (74%),
      terminal cancer (8%), and severe trauma (7%). The most common incident locations
      were the patient's home and nursing homes. These locations were more common in
      the group where resuscitation was not attempted and these patients were older and
      the proportions of females and asystole were significantly higher. Bystander CPR
      was provided in 82 (16%) overall, but only in 8 (3%) in the group where
      resuscitation was not attempted. CONCLUSION: Survival to discharge from hospital
      in all cases of OHCA was 6.2% but 20.5% in witnessed, presumed cardiac aetiology
      in VF. The decision to withhold resuscitation was based upon presumed prolonged
      anoxia in the majority of cases.

PMID- 15582765
TI  - CPR courses and semi-automatic defibrillators--life saving in cardiac arrest?
AB  - OBJECTIVES: The aim was to assess the knowledge of life-supporting first-aid in
      both cardiac arrest survivors and relatives, and their willingness to have a semi
      automatic external defibrillator in their homes and use it in an emergency.
      MATERIAL AND METHODS: Cardiac arrest survivors, their families, friends,
      neighbours and co-workers were interviewed by medical students using prepared
      questionnaires. Their knowledge and self-assessment of life-supporting first-aid,
      their willingness to have a semi-automatic defibrillator in their homes and their
      willingness to use it in an emergency before and after a course in
      cardiopulmonary resuscitation (CPR) with a semi-automatic external defibrillator
      was evaluated. Courses were taught by medical students who had received special
      training in basic and advanced life support. RESULTS: Both patients and
      relatives, after a course of 2-3 h, were no longer afraid of making mistakes by
      providing life-supporting first-aid. The automated external defibrillator (AED)
      was generally accepted and considered easy to handle. CONCLUSION: We consider
      equipping high-risk patients and their families with AEDs as a viable method of
      increasing their survival in case of a recurring cardiac arrest. This, of course,
      should be corroborated by further studies.

PMID- 15582766
TI  - Teaching public access defibrillation to lay volunteers--a professional health
      care provider is not a more effective instructor than a trained lay person.
AB  - BACKGROUND: Survival improves in witnessed out-of-hospital cardiac arrest if the
      victim receives bystander-initiated cardiopulmonary resuscitation and rapid
      defibrillation (BLS/AED). The European Resuscitation Council has a simple
      programme to teach these life-saving skills that require no previous experience
      of automated external defibrillators (AEDs). To be able to implement the use of
      AEDs widely, many instructors are needed, and therefore, lay persons may also be
      used as trainers. The purpose of this randomized study was to compare lay
      volunteers trained by a lay person with those trained by a health care
      professional using the Objective Structured Clinical Examination (OSCE). METHODS:
      Eight instructors, including four lay persons and four health care professionals,
      were given a basic course and an instructor course in CPR-D by the same
      instructor. All newly trained instructors trained 38 lay volunteers (19 pairs)
      who had no previous training in the use of a defibrillator. The lay volunteers
      performed the OSCE 2-3 weeks after the course. The OSCE comprised two scenarios
      with a manikin: the first, a patient in cardiac arrest with ventricular
      fibrillation, and the second, an imminent cardiac arrest with asystole as the
      initial rhythm. The same OSCE was performed by a group of lay first aiders
      practicing every 2 weeks who served as the control group. RESULTS: No statistical
      difference was present between the two groups of lay volunteers in the OSCE. All
      were able to use the AED and follow instructions. They identified patients with
      ventricular fibrillation and cardiac arrest, but had difficulties identifying
      cases with imminent cardiac arrest. The control group of trained first aiders
      performed significantly more effectively than the newly trained lay persons.
      CONCLUSIONS: No significant benefit exists in the trainer being a health care
      professional, but thorough training and subsequent rehearsing of the skills
      learned are crucial.

PMID- 15582767
TI  - Characteristics and outcome of cardiorespiratory arrest in children.
AB  - OBJECTIVE: To analyse the present day characteristics and outcome of cardio
      respiratory arrest in children in Spain. DESIGN: An 18-month prospective,
      multicentre study analysing out-of-hospital and in-hospital cardio-respiratory
      arrest in children. PATIENTS AND METHODS: Two hundred and eighty-three children
      between 7 days and 17 years of age with cardio-respiratory arrest. Data were
      recorded according to the Utstein style. The outcome variables were the sustained
      return of spontaneous circulation (initial survival), and survival at 1 year
      (final survival). Three hundred and eleven cardio-respiratory arrest episodes,
      composed of 70 respiratory arrests and 241 cardiac arrests in 283 children were
      studied. Accidents were the most frequent cause of out-of-hospital arrest (40%),
      and cardiac disease was the leading cause (31%) of in-hospital arrest. Initial
      survival was 60.2% and 1 year survival was 33.2%. The final survival was higher
      in patients with respiratory arrest (70%) than in patients with cardiac arrest
      (21.1%) (P <0.0001). Although many individual factors correlated with mortality,
      multivariate logistic regression revealed that the best indicator of mortality
      was a duration of cardiopulmonary resuscitation of over 20 min (odds ratio:
      10.35; 95% CI 4.59-23.32). CONCLUSIONS: In Spain, the present mortality from
      cardio-respiratory arrest in children remains high. Survival after respiratory
      arrest is significantly higher than after cardiac arrest. The duration of
      cardiopulmonary resuscitation attempt is the best indicator of mortality of
      cardio-respiratory arrest in children.

PMID- 15582768
TI  - Ambulance alerting of paediatric emergencies to a general hospital.
AB  - BACKGROUND: There are at present only a small number of dedicated paediatric
      emergency departments in the UK. Severely ill and injured children are often
      taken by ambulance to the nearest general hospital. Efforts have been made to
      provide better care for these sickest children pending the establishment of
      dedicated paediatric emergency services within general emergency departments by
      2004 [Royal College of Paediatrics and Child Health; Accident and Emergency
      Services for Children-Report of a Multidisciplinary Working Party, June 1999]. To
      learn more of the staffing implications for the establishment of dedicated
      paediatric emergency units within the general hospital, 30 months of paediatric
      alert call data are presented. METHODS: A prospective review of paediatric alert
      calls over 30 months, (from January 1999 until June 2001). All alert calls from
      the ambulance service to a large urban emergency department were recorded on a
      specific form. Data from these forms is presented. RESULTS: There were 1754 alert
      calls of all types during this 30-month period, of which 153 (9%) were for
      patients under the age of 16 (mean 1.2 each week). Of these, 102 (66%) were for
      medical conditions and 51 (34%) were for trauma. The mean estimated time of
      arrival from the time of the alert call was 6 min. The majority of both medical
      and trauma paediatric alert calls occur in the afternoon and progress well into
      the night. The 51.6% of paediatric medical alert calls and 64.4% of paediatric
      trauma alert calls occur 'out of normal hours'. There was little reduction in the
      frequency of alert calls at the weekend. There were no paediatric trauma alert
      calls between 2 a.m. and 10 a.m., although medical paediatric alert calls
      continued throughout the night. CONCLUSIONS: Resident senior trauma personnel to
      manage injured children should be provided until at least midnight. Hospitals
      that maintain a facility for the reception of sick children must be able to
      provide a rapid response to paediatric medical emergencies on a 24 h basis.
      Guidelines for alert calls for ambulance crews are required.

PMID- 15582769
TI  - Skeletal chest injuries secondary to cardiopulmonary resuscitation.
AB  - OBJECTIVE: To review the evidence on the incidence of rib and sternal fractures
      after conventional closed-chest compression in the treatment of cardiac arrest in
      adults and children, and after active compression-decompression cardiopulmonary
      resuscitation (ACD-CPR). METHODS: Medline search and additional review of the
      cited literature in the articles found. RESULTS: Reports on conventional CPR in
      adults suggest an incidence of rib fractures ranging from 13 to 97%, and of
      sternal fractures from 1 to 43%. Reports on CPR in children suggest an incidence
      of rib fractures of 0-2%, and no sternal fractures. ACD-CPR has been reported as
      causing rib fractures in 4-87%, and sternal fractures in 0-93% of cases.
      CONCLUSIONS: Sound methodological studies on thoracic fractures due to chest
      compression do not exist and the available studies cannot be compared one with
      another. In infants and toddlers, manual CPR rarely causes skeletal chest
      injuries. In adults, sternal fractures occur in at least one-fifth and rib
      fractures as well as rib and/or sternal fractures in at least one-third of the
      patients during conventional CPR. There is no compelling evidence to show that an
      increased complication rate is associated with ACD-CPR. Rib or sternal fractures
      are unlikely to increase mortality, as they rarely cause severe internal organ
      damage. Further prospective studies are desirable to assess complications by post
      mortem examinations that explicitly address them. In particular, clinical
      evaluation of mechanical CPR devices should be accompanied by a thorough
      assessment of the associated complications because data specific to this modality
      are not available.

PMID- 15582770
TI  - Chest wall injuries following cardiopulmonary resuscitation.
AB  - The forensic records were reviewed of 1823 deaths referred to Edinburgh City
      Mortuary for autopsy over a 15-month period, 2000-2001; 499 cases (343 males, 156
      females) that received CPR prior to death were studied. Rib fractures were found
      in 29%, sternal fracture in 14%, and 11% of cases showed external chest wall
      bruising or abrasion. More females sustained rib fractures than males (37% versus
      26%; P <0.05). There was no significant gender difference for sternal fracture
      (females 17%, males 12%; P=0.051). The incidence of rib fractures increased with
      age (P <0.001). There was no significant difference in the number of left or
      right ribs fractured (P=0.631). This study incorporates all cases of in and out
      of-hospital CPR and does not discriminate for the CPR provider or technique
      employed, therefore, providing a current and representative overview of the
      incidence of rib and sternal fractures in non-survivors of CPR.

PMID- 15582771
TI  - Thyroid storm concealing diabetic ketoacidosis leading to cardiac arrest.

PMID- 15582772
TI  - Emergency call confusion.

PMID- 15582773
TI  - Diazepam for treatment of massive chloroquine intoxication.

PMID- 15582774
TI  - Left-right asymmetry in embryonic development: a comprehensive review.
AB  - Embryonic morphogenesis occurs along three orthogonal axes. While the patterning
      of the anterior-posterior and dorsal-ventral axes has been increasingly well
      characterized, the left-right (LR) axis has only recently begun to be understood
      at the molecular level. The mechanisms which ensure invariant LR asymmetry of the
      heart, viscera, and brain represent a thread connecting biomolecular chirality to
      human cognition, along the way involving fundamental aspects of cell biology,
      biophysics, and evolutionary biology. An understanding of LR asymmetry is
      important not only for basic science, but also for the biomedicine of a wide
      range of birth defects and human genetic syndromes. This review summarizes the
      current knowledge regarding LR patterning in a number of vertebrate and
      invertebrate species, discusses several poorly understood but important
      phenomena, and highlights some important open questions about the evolutionary
      origin and conservation of mechanisms underlying embryonic asymmetry.

PMID- 15582775
TI  - Glial cell-line derived neurotrophic factor-dependent fusimotor neuron survival
      during development.
AB  - Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor
      for motor neurons. Previous studies have shown that some motor neurons depend
      upon GDNF during development but this GDNF-dependent motor neuron subpopulation
      has not been characterized. We examined GDNF expression patterns in muscle and
      the impact of altered GDNF expression on the development of subtypes of motor
      neurons. In GDNF hemizygous mice, motor neuron innervation to muscle spindle
      stretch receptors (fusimotor neuron innervation) was decreased, whereas in
      transgenic mice that overexpress GDNF in muscle, fusimotor innervation to muscle
      spindles was increased. Facial motor neurons, which do not contain fusimotor
      neurons, were not changed in number when GDNF was over expressed by facial
      muscles during their development. Taken together, these data indicate that
      fusimotor neurons depend upon GDNF for survival during development. Since the
      fraction of cervical and lumbar motor neurons lost in GDNF-deficient mice at
      birth closely approximates the size of the fusimotor neuron pool, these data
      suggest that motor neuron loss in GDNF-deficient mice may be primarily of
      fusimotor neuron origin.

PMID- 15582776
TI  - Hedgehog and retinoid signalling confines nkx2.2b expression to the lateral floor
      plate of the zebrafish trunk.
AB  - The ventral neural tube of vertebrates consists of distinct neural progenitor
      domains positioned along the dorsoventral (DV) axis that develop different types
      of moto- and interneurons. Several signalling molecules, most notably Sonic
      Hedgehog (Shh), retinoic acid (RA) and fibroblast growth factor (FGF) have been
      implicated in the generation of these domains. Shh is secreted from the floor
      plate, the ventral most neural tube structure that consists of the medial (MFP)
      and the lateral floor plate (LFP). While the MFP is well characterized,
      organization and function of the LFP remains unclear. Here, we describe the novel
      homeobox gene nkx2.2b that is strongly expressed in the trunk LFP of zebrafish
      and thus represents a unique marker for the characterization of LFP formation and
      the identification of LFP deficient mutants. nkx2.2b and its paralog nkx2.2a
      (formerly known as nk2.2 and nkx2.2) arose by gene duplication in zebrafish. Both
      duplicates show significant differences in their expression patterns. For
      example, while prominent nkx2.2a expression has been described in the ventral
      brain [Barth, K.A., Wilson, S.W., 1995. Expression of zebrafish nk2.2 is
      influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of
      neuronal differentiation in the embryonic forebrain. Development 121, 1755-1768],
      hardly any expression can be found in the trunk LFP, which is in contrast to
      nkx2.2b. Overexpression, mutant and inhibitor analyses show that nkx2.2b
      expression in the LFP is up-regulated by Shh, but repressed by retinoids and
      ectopic islet-1 (isl1) expression. In contrast to previously described zebrafish
      trunk LFP markers, like e.g. tal2 or foxa2, nkx2.2b is exclusively expressed in
      the LFP. Thus, it represents a unique tool to analyse the mechanisms of ventral
      neural tube patterning in zebrafish.

PMID- 15582777
TI  - Convergent proliferative response and divergent morphogenic pathways induced by
      epicardial and endocardial signaling in fetal heart development.
AB  - Heart development requires cardiomyocyte proliferation, coupled with morphogenic
      differentiation of the inner trabecular myocardium and the outer compact zone
      myocardium. In mouse embryos lacking the retinoic acid receptor RXRalpha,
      proliferation and morphogenesis of the compact zone fails. We demonstrated
      previously that epicardial cells, in response to retinoic acid, secrete an
      activity that promotes cell proliferation. In this study, we have investigated
      downstream signaling pathways that are elicited in response to this factor. We
      find that cells treated in culture activate PI3 kinase and Erk pathways, and that
      these are required for a proliferative response. In vivo, phosphorylation of Akt
      and GSK3beta (PI3K pathway) and of Erk1/2 and p90rsk (Erk pathway) is
      substantially reduced in RXRalpha-deficient heart tissue. Neuregulin, a mitogen
      secreted from the endocardium which promotes cardiomyocyte proliferation and
      trabecular differentiation, also activates proliferation via PI3K and Erk
      pathways. However, the epicardial factor is not neuregulin, and does not function
      via the neuregulin receptor. Gene markers known to be selectively expressed in
      trabecular or compact myocardium in vivo are differentially activated in cell
      culture by treatment with neuregulin or epicardial factor, and are misexpressed
      in RXRalpha(-/-) heart tissue. We therefore conclude that epicardial and
      endocardial signals converge on common proliferative components, but diverge in
      downstream pathways that lead to compact vs. trabecular morphogenic
      differentiation.

PMID- 15582778
TI  - Pluripotential competence of cells associated with Nanog activity.
AB  - Nanog is a novel pluripotential cell-specific gene that plays a crucial role in
      maintaining the undifferentiated state of early postimplantation embryos and
      embryonic stem (ES) cells. We have explored the expression pattern and function
      of Nanog and a Nanog-homologue, Nanog-ps1.Nanog-ps1 was mapped on Chromosome 7
      and shown to be a pseudogene. Immunocytochemical analysis in vivo showed that the
      NANOG protein was absent in unfertilized oocytes, and was detected in cells of
      morula-stage embryos, the inner cell mass of blastocysts and the epiblast of E6.5
      and E7.5 embryos, but not in primordial germ cells of early postimplantation
      embryos. In monkey and human ES cells, NANOG expression was restricted to
      undifferentiated cells. Furthermore, reactivation of the somatic cell-derived
      Nanog was tightly linked with nuclear reprogramming induced by cell hybridization
      with ES cells and by nuclear transplantation into enucleated oocytes. Notably,
      mouse Nanog (+/-) ES cells, which produced approximately half the amount of NANOG
      produced by wild-type ES cells, readily differentiated to multi-lineage cells in
      culture medium including LIF. The labile undifferentiated state was fully rescued
      by constitutive expression of exogenous Nanog. Thus, the activity of Nanog is
      tightly correlated with an undifferentiated state of cells even in nuclear
      reprogrammed somatic cells. Nanog may function as a key regulator for sustaining
      pluripotency in a dose-dependent manner.

PMID- 15582779
TI  - The relative role of the T-domain and flanking sequences for developmental
      control and transcriptional regulation in protein chimeras of Drosophila OMB and
      ORG-1.
AB  - optomotor-blind (omb) and optomotor-blind related-1 (org-1) encode T-domain DNA
      binding proteins in Drosophila. Members of this family of transcription factors
      play widely varying roles during early development and organogenesis in both
      vertebrates and invertebrates. Functional specificity differs in spite of similar
      DNA binding preferences of all family members. Using a series of domain swap
      chimeras, in which different parts of OMB and ORG-1 were mutually exchanged, we
      investigated the relevance of individual domains in vitro and in vivo. In cell
      culture transfection assays, ORG-1 was a strong transcriptional activator,
      whereas OMB appeared neutral. The main transcriptional activation function was
      identified in the C-terminal part of ORG-1. Also in vivo, OMB and ORG-1 showed
      qualitative differences when the proteins were ectopically expressed during
      development. Gain-of-function expression of OMB is known to counteract eye
      formation and resulted in the loss of the arista, whereas ORG-1 had little effect
      on eye development but caused antenna-to-leg transformations and shortened legs
      in the corresponding gain-of-function situations. The functional properties of
      OMB/ORG-1 chimeras in several developmental contexts was dominated by the origin
      of the C-terminal region, suggesting that the transcriptional activation
      potential can be one major determinant of developmental specificity. In late eye
      development, we observed, however, a strong influence of the T-domain on
      ommatidial differentiation. The specificity of chimeric omb/org-1transgenes,
      thus, depended on the cellular context in which they were expressed. This
      suggests that both transcriptional activation/repression properties as well as
      intrinsic DNA binding specificity can contribute to the functional
      characteristics of T-domain factors.

PMID- 15582780
TI  - The Ste20-like kinase misshapen functions together with Bicaudal-D and dynein in
      driving nuclear migration in the developing drosophila eye.
AB  - Nuclear translocation, driven by the motility apparatus consisting of the
      cytoplasmic dynein motor and microtubules, is essential for cell migration during
      embryonic development. Bicaudal-D (Bic-D), an evolutionarily conserved dynein
      interacting protein, is required for developmental control of nuclear migration
      in Drosophila. Nothing is known about the signaling events that coordinate the
      function of Bic-D and dynein during development. Here, we show that Misshapen
      (Msn), the fly homolog of the vertebrate Nck-interacting kinase is a component of
      a novel signaling pathway that regulates photoreceptor (R-cell) nuclear migration
      in the developing Drosophila compound eye. Msn, like Bic-D, is required for the
      apical migration of differentiating R-cell precursor nuclei. msn displays strong
      genetic interaction with Bic-D. Biochemical studies demonstrate that Msn
      increases the phosphorylation of Bic-D, which appears to be necessary for the
      apical accumulation of both Bic-D and dynein in developing R-cell precursor
      cells. We propose that Msn functions together with Bic-D to regulate the apical
      localization of dynein in generating directed nuclear migration within
      differentiating R-cell precursor cells.

PMID- 15582781
TI  - Motility of endodermal epithelial cells plays a major role in reorganizing the
      two epithelial layers in Hydra.
AB  - Cell-cell interactions and cell rearrangements play important roles during
      development. Aggregates of Hydra cells reorganize into the two epithelial layers
      and subsequently form a normal animal. Examination of the formation of the two
      layers under various situations, indicates that the motility of endodermal
      epithelial cells, but not the differential adhesive forces of the two types of
      epithelial cells, plays the critical role in setting up the two epithelial
      layers. (1) When aggregates of ectodermal cells and of endodermal cells were
      placed in direct contact, the endodermal cells migrated into the interior of the
      ectodermal aggregate. This process was completely inhibited by cytochalasin B
      although initial firm attachment between the two aggregates was not blocked. (2)
      A single endodermal epithelial cell placed in contact with an ectodermal
      aggregate, actively extended pseudopod-like structures and migrated toward the
      center of the ectodermal aggregate. In contrast, an ectodermal epithelial cell
      remained in contact with an endodermal aggregate and never exhibited migratory
      behavior. Cytochalasin treatment of only endodermal epithelial cells abolished
      the migration. (3) One to 4 endodermal epithelial cells and/or ectodermal
      epithelial cells were placed in contact with one another forming up to 4-cell
      aggregates. Endodermal epithelial cells exhibited high motility that can be
      attributed to the migratory movement described above. Finally, formation of actin
      bundles, as visualized with rhodamine-phalloidin, was always correlated with
      pseudopod formation in endodermal epithelial cells during early and mid stages of
      aggregate formation.

PMID- 15582782
TI  - Complexity and the future of the patient-doctor relationship.

PMID- 15582783
TI  - Doctors' responses to medical errors.
AB  - Medical error has become a topic of much concern in recent years. Doctors'
      responses to their own or others' medical errors are important because openness
      or secrecy has an impact on efforts to reduce iatrogenic injury, on malpractice
      litigation, and on patient and doctor satisfaction with care. This article
      reviews doctor's responses to error within the context of contemporary medical
      care and considers themes that emerge from this review.

PMID- 15582784
TI  - Evolution of truth-telling attitudes and practices in Italy.
AB  - The debate on truth telling is at the core of contemporary biomedical ethics.
      Differences in truth telling arise from the delicate interplay between autonomy
      and beneficence in medicine, under the influence of cultural variables. Recently,
      a trend toward evolution of truth-telling practices has been noticed in countries
      previously known for non-disclosure. Italy is among them. This article analyzes
      in detail the different factors that have been influential in the Italian
      context, focusing on cancer patients. Medical profession, public discourse,
      medical deontology and legislators played an important role in Italy's shift
      toward the western autonomy predicament. A review of the scanty published data on
      informed consent and truth telling in Italy, however, consistently shows that
      partial or non-disclosure are still present. This seems to represent a general
      trend in nations traditionally centered on family and community values. The
      article explores these issues to achieve a better understanding of the specific
      Italian cultural context, while avoiding common stereotyping. The subject treated
      contributes to the growing debate on cultural diversity in medicine and in
      oncology.

PMID- 15582785
TI  - Pharmacokinetic studies in children with cancer.
AB  - We reviewed the current status of our knowledge of pharmacokinetics and
      pharmacodynamics of some anti-neoplastic drugs, used in the treatment of
      childhood cancer. Extrapolation of data from pharmacokinetic studies in adults to
      the paediatric population is often not feasible. Specific studies in children are
      needed. Of all reviewed anti-neoplastic drugs methotrexate appears to be most
      extensively studied. Methotrexate pharmacokinetics is correlated with toxicity
      and response to therapy, and it has been shown that individualized adaptive
      dosing of methotrexate is correlated with a better response to therapy without
      increasing toxicity in children with ALL and osteosarcoma. Of most of the other
      reviewed anti-neoplastic drugs it is demonstrated that pharmacokinetics is
      correlated with toxicity, and of some drugs a relationship of pharmacokinetics
      with response to therapy is demonstrated as well. In case of cytarabine,
      etoposide, and teniposide, individualized dosing also appears to be feasible.
      However, there is no evidence that this strategy improves response to therapy.
      Specifically data on pharmacokinetic and pharmacodynamic correlations and effect
      of pharmacokinetically guided, individualized dosing are important for the design
      of optimal cancer chemotherapy for individual patients. Unfortunately for a
      considerable number of anti-neoplastic drugs these specific data are lacking in
      children and future research is needed.

PMID- 15582786
TI  - The pathogenesis and treatment of brain metastases: a comprehensive review.
AB  - Brain metastases are the most common intracranial tumors and their incidence is
      increasing. Untreated brain metastases are associated with a poor prognosis and a
      poor performance status. The role of surgery in the management of multiple brain
      metastases is still controversial. As more than 70% of patients have multiple
      metastases at the time of diagnosis, whole brain radiotherapy is the treatment of
      choice in most cases. Brain metastases are an ideal target for stereotactic
      radiosurgery, as they are better circumscribed than primary brain tumors.
      Currently, chemotherapy has a limited role in the treatment of most brain
      metastases. Several new therapies, with a good penetration through the blood
      brain barrier, such as temozolomide, have been used in brain metastases with
      different results depending on the histology of the primary tumor. A better
      understanding of the complex processes underlying the development of brain
      metastasis will enable us to develop more satisfactory targeted treatments.

PMID- 15582787
TI  - When Pasteur went to China.

PMID- 15582788
TI  - Prenatal diagnosis for Joubert syndrome?

PMID- 15582789
TI  - Sugar directly triggers fat formation.

PMID- 15582790
TI  - Exploiting toll-like receptors for designed multiple ligands.

PMID- 15582791
TI  - All systems go?

PMID- 15582792
TI  - Molecular targets and cancer therapeutics.

PMID- 15582793
TI  - Therapeutic scope of modulation of non-voltage-gated cation channels.
AB  - Although widely regarded as attractive drug targets, less than a tenth of known
      ion channels are currently commercially exploited as therapeutic targets.
      Historically, drug discovery efforts on ion channel targets have been encumbered
      by a lack of molecular and structural information, sub-optimal screening
      technologies and a paucity of discriminating pharmacological tools. Although
      challenges remain, recent scientific and technological advances in the area of
      ion channel research and screening offer the exciting prospect of a new, more
      predictive era of ion channel drug discovery. In this article, focusing primarily
      on non-voltage-gated cation channels, we describe the continuing evolution of
      approaches to ion channel drug discovery, highlight recent developments in the
      ion channel field and consider their potential impact on discovering and
      ascribing function to ion channel targets. We discuss the renaissance of known
      ion channel targets, such as nicotinic acetylcholine receptors and calcium
      activated potassium channels, as well as the emergence of the transient receptor
      potential (TRP) channels as a gene family of cation channels with broad
      therapeutic potential.

PMID- 15582794
TI  - Improving the decision-making process in structural modification of drug
      candidates: reducing toxicity.
AB  - The rule of three, relating to activity-exposure-toxicity, presents the single
      most difficult challenge in the design and advancement of drug candidates to the
      development stage. Absorption, distribution, metabolism and excretion (ADME)
      studies are widely used in drug discovery to optimize this balance of properties
      necessary to convert lead compounds into drugs that are both safe and effective
      for human patients. Idiosyncratic drug reactions (IDRs; referred to as type B
      reactions, which are mainly caused by reactive metabolites) are one type of
      adverse drug reaction that is important to human health and safety. This review
      highlights the strategies for the decision-making process involving substructures
      that, when found in drugs, can form reactive metabolites and are involved in
      toxicities in humans; the tools used to reduce IDRs are also discussed. Several
      examples are included to show how toxicity studies have influenced and guided
      drug design. Investigations of reactive intermediate formation in subcellular
      fractions with the use of radiolabeled reagents are also discussed.

PMID- 15582795
TI  - Quantum dots and other nanoparticles: what can they offer to drug discovery?
AB  - Nanocrystals (quantum dots) and other nanoparticles (gold colloids, magnetic
      bars, nanobars, dendrimers and nanoshells) have been receiving a lot of attention
      recently with their unique properties for potential use in drug discovery,
      bioengineering and therapeutics. In this review, structural, optical and
      biological assets of nanocrystals are summarized and their applications to drug
      discovery studies are discussed. Unique properties of these nanoparticles can
      offer new advancements in drug discovery.

PMID- 15582796
TI  - High-throughput multiplexed capillary electrophoresis in drug discovery.
AB  - The demand for high-throughput analytical tools to support drug discovery
      applications has led to the development of multiplexed capillary electrophoresis
      and multichannel microfluidic devices to characterize libraries of compounds and
      alleviate backlogs in the discovery process. The capability to analyze multiple
      samples in parallel, and the diverse separation conditions that are permissible,
      facilitates rapid turnaround times. Examples of high-throughput applications of
      multiplexed electrophoresis in drug discovery include: physicochemical profiling,
      enzyme analysis, chiral separations and protein/metabolite analysis. Many single
      capillary electrophoresis methods can be potentially adapted to a multiplexed
      format, therefore, we anticipate the development of other high-throughput
      applications in the near future, which should facilitate decreases in sample
      analysis time and help improve laboratory efficiency.

PMID- 15582801
TI  - Determination of nucleic acids at nanogram level using resonance light scattering
      technique with Congo Red.
AB  - Based on the enhancement of the resonance light scattering (RLS) of Congo Red
      (CR) by nucleic acid, a new quantitative method for nucleic acid is developed. In
      the Tris-HCl buffer (pH 10.5), the weak light scattering of CR is greatly
      enhanced by addition of nucleic acid and CTMAB, the maximum peak is at 560 nm and
      the enhanced intensity of RLS is in proportion to the concentration of nucleic
      acid. The linear range is 1.0 x 10(-9) to 1.0 x 10(-6) g ml(-1), 7.5 x 10(-8) to
      1.0 x 10(-6) g ml(-1) and 7.5 x 10(-8) to 2.5 x 10(-6) g ml(-1) for herring sperm
      DNA, calf thymus DNA and yeast RNA, and the detection limits are 0.019, 0.89 and
      1.2 ng ml(-1) (S/N = 3), respectively. Actual biological samples were
      satisfactorily determined.

PMID- 15582802
TI  - Near-infrared spectroscopy of autunites.
AB  - NIR spectroscopy has been applied to the study water in the interlayer of the
      autunite minerals. The spectra of autunites and metaautunites in the first HOH
      fundamental overtone are different and the spectra of autunites of different
      origins in the 6000-7500 cm(-1) region are considerably different. A number of
      conclusions are made based upon the NIR spectra: (a) The spectra of different
      autunites are different in the NIR spectral region; (b) the spectra of
      metaautunites show similarity; (c) the spectra of metaautunites are different
      from that of autunites. NIR spectroscopy provides a method of determination of
      the structure of water in the interlayer of natural autunites. The implication
      from the variation in the NIR spectra is that the structural arrangement of water
      for different autunites is different and is sample dependent. NIR spectroscopy
      has a wide potential for the study of the autunite minerals.

PMID- 15582803
TI  - Theoretical study of structure, stability and infrared spectra of CH3X-SO3 (X =
      F, Cl, Br) complexes.
AB  - Ab initio computational study of the electronic structure and infrared spectra of
      donor-acceptor complexes formed between SO3 and CH3X (X = F, Cl, Br) molecules
      was carried out at the MP2(full)/6-31G(d) level of theory. The calculated
      complexation energy at G2MP2 level shows that stability of complexes decrease, as
      CH3Cl-SO3 > CH3Br-SO3 > CH3F-SO3. The NBO partitioning scheme show that the
      lengthening of the C-F, C-Cl, and C-Br bond lengths, upon complexation, is due to
      an decreasing "s" character in these bonds.

PMID- 15582804
TI  - FT-Raman and FTIR spectra, assignments and ab initio calculations of 2
      aminobenzyl alcohol.
AB  - The Fourier transform Raman and Fourier transform infrared spectra of 2
      aminobenzyl alcohol (2ABA) were recorded in the solid phase. Geometry
      optimizations were done with out any constraint and harmonic vibrational wave
      numbers and several thermodynamic parameters were calculated for the minimum
      energy conformer at ab initio and DFT levels invoking 6-31g** and 6-311+g(2d, p)
      basis sets and the results were compared with the experimental values. With the
      help of three specific scaling procedures, the observed vibrational wavenumbers
      in FTIR and FT-Raman spectra were analyzed and assigned to different normal modes
      of the molecule. Most of the modes have wavenumbers in the expected range and the
      error obtained was in general very low. The appropriate theoretical spectrograms
      for the Raman and IR spectra of 2ABA were also constructed.

PMID- 15582805
TI  - Structural and vibrational study of a new organic hydrogen sulfate.
AB  - This paper presents a structural and vibrational study of a new compound, namely,
      monohydrate 1,5-pentanediammonium hydrogen sulfate (NH3(CH2)5NH3(HSO4)2.H2O). The
      X-ray crystal structure shows that this compound crystallizes in the monoclinic
      system, space group P2(1)/c, with the lattice parameters a=9.2250(2)A,
      b=7.7540(4)A, c=20.8520(1)A, beta=116.23(3) degrees, V=1337.97(10)A3, and Z=4.
      From the structural investigations, it is found that the studied compound is
      built by infinite anionic ribbons parallel to the "a" axis. These ribbons form
      tunnels in which organic cations are inserted. Infrared (IR) spectrum of the
      compound in the 300-4000 cm(-1) spectral region is reported. A tentative
      assignment of the observed bands, supported by a molecular orbital semi-empirical
      calculation, is given.

PMID- 15582806
TI  - Partitioning of quencher ions in the micellar microenvironment of polyoxyethylene
      nonyl phenol.
AB  - This paper has explored the quenching of fluorescence of the dye safranine T (ST)
      by the inorganic cations viz Cu2+, Co2+, Ni2+ and Mn2+ in micellar solutions of
      the surfactant dioxyethylene nonyl phenol (Igepal CO-210), pentaoxyethylene nonyl
      phenol (Igepal CO-520) and dodecaoxyethylene nonyl phenol (Igepal CO-720). The
      quenching results have been calculated in light of stern volmer equation (SV) to
      evaluate the extent of interaction between the fluorophore (ST) and quencher. The
      average concentration of the quencher ions in the micelle have been determined.
      The quenching efficiency of ST by inorganic ions in micellar medium is lower than
      that in aqueous medium. The results show that the ions get partitioned in the
      micellar medium. The values of the partition coefficient of the ions decrease
      with increase in HLB value and number of oxyethylene groups in Igepal.

PMID- 15582807
TI  - Spectroscopic studies on the cation-anion, cation-solvent and anion-solvent
      interactions in the LiCF3SO3/acetamide complex system.
AB  - A molten salt electrolyte composed of lithium triflate (LiCF3SO3) and acetamide
      (CH3CONH2) has been prepared and characterized by Raman, IR spectroscopy and ac
      impedance. It is found that acetamide molecule not only complexes with the Li+
      cation but also interacts with the CF3SO3- anion via hydrogen bonding due to its
      two polar groups (C=O group and NH2 group) capable of coordinating with cations
      and anions, respectively. Cation-anion interaction is strengthened while cation
      solvent and anion-solvent interactions are weakened with the increases of salt
      concentration and temperature in the LiCF3SO3/acetamide complex. The ionic
      conductivities of the LiCF3SO3/acetamide complex with different molar ratios
      depend strongly on the ionic association in the complex system.

PMID- 15582808
TI  - Comparative study on the inclusion behavior between meso-tetrakis(4-N
      ethylpyridiniurmyl)porphyrin and beta-cyclodextrin derivatives.
AB  - 5,10,15,20-Tetrakis(4-N-ethylpyridiniurmyl)porphyrin (TEPyP) formed 1:1
      stoichiometry inclusion complexes with beta-cyclodextrin (beta-CD) and its
      derivatives including hydroxypropyl-beta-cyclodextrin (HP-beta-CD),
      sulfobutylether-beta-cyclodextrin (SBE-beta-CD) in basic aqueous solution. The
      supramolecular system was investigated by the methods of fluorescence, UV-vis
      absorption spectroscopy, nuclear magnetic resonance (NMR) technique. The
      inclusion ability of cyclodextrins exhibited remarkable difference for beta-CD,
      HP-beta-CD and SBE-beta-CD. Association constants as high as K=1.1 x 10(4) M(-1)
      in the case of HP-beta-CD/TEPyP and 2.0 x 10(5) M(-1) in the case of SBE-beta
      CD/TEPyP complexes were determined, whereas a lower value (K=550 M(-1)) was given
      in the case of beta-CD/TEPyP. The results showed that hydrogen bonding and charge
      attraction play important roles in the processes of host-guest interaction. The
      interaction mechanism of inclusion processes could be explained by the analysis
      of NMR spectroscopy. The supramolecular assembly was formed. beta-CD and HP-beta
      CD approached from the primary face of cavities of CDs.

PMID- 15582809
TI  - [Theoretical and experimental vibrational spectroscopy study of K3Ln(PO4)2
      phosphates].
AB  - The monoclinic phosphates with K3Ln(PO4)2 (Ln=rare earth) formula were
      synthesized. Their infrared and Raman spectra have been reported and analysed.
      The results of a force field calculation for K3Nd(PO4)2 are presented.

PMID- 15582810
TI  - Optical properties of Dy3+ doped in oxyfluoroborate glass.
AB  - Optical absorption, fluorescence and photoacoustic spectra of Dy3+ doped in
      oxyfluoroborate glass has been studied. Lifetime of 4F(9/2) level has been
      measured for different concentration of Dy3+. Effect of concentration quenching
      on the lifetime and the fluorescence yield has been observed and the mechanism of
      energy transfer discussed. The energy transfer from Pr3+ to Dy3+ has been
      observed and explained in a codoped glass containing Pr3+ + Dy3+.

PMID- 15582811
TI  - Electronic, cyclic voltammetry, IR and EPR spectral studies of copper(II)
      complexes with 12-membered N4, N2O2 and N2S2 donor macrocyclic ligands.
AB  - A new series of copper(II) complexes have been synthesized with macrocyclic
      ligands having three different donating atoms in the macrocyclic ring. It has
      been shown that the stereochemistry of complexes is dependent on the coordinated
      anions. These complexes are characterized by various physicochemical techniques,
      viz. elemental analysis, molar conductance, magnetic susceptibility measurements,
      IR, electronic, 1H NMR and EPR spectral studies. Cyclic voltammetric behavior of
      the complexes has also been discussed. The observed anisotropic g-values indicate
      that the chloro and acetato complexes are six-coordinate tetragonal. Whereas the
      sulfato and nitrato complexes are found to have five-coordinate square-pyramidal
      and four-coordinate square-planar geometry, respectively.

PMID- 15582812
TI  - Application of light-absorption ratio variation approach as an optimum
      spectrophotometry to determination of Mn(II) in ng ml(-1) level using a
      competitive replacement complexation.
AB  - The light-absorption ratio variation approach (LARVA) which produces an
      outstandingly increasing of analytical sensitivity was applied to the
      quantitative detection of ultramicro amounts of Mn(II) by light-absorption
      spectrometry using the competitive replacement complexation among 1,5-di(2
      hydroxy-5-sulfophenyl)-3-cyanoformazan (DSPCF), Zn(II) and Mn(II) in the presence
      of o-phenanthroline (OPTL). Not only masks OPTL foreign metal ions but also
      seriously sensitize the competitive complexation. All the binary and ternary
      complexes were characterized by the break point approach. Results have shown that
      the limit of detection (3delta) of Mn(II) is only 0.7 ng ml(-1). This method has
      been applied to analysis of water quality with satisfactory results.

PMID- 15582813
TI  - Infrared intensities of some SiH-containing compounds in the gas-phase.
AB  - Infrared intensities measured in the gas-phase are reported for CH3SiH3, CH3SiD3,
      (CH3)2SiH2, (CH3)2SiD2, (SiH3)2CH2, (SiD3)2CH2, Si2H6, SiH2Cl2 and (SiH3)2O.
      These are compared with theoretical estimates from HF, MP2 and B3LYP calculations
      with the 6-311G** basis set. Literature values of nuCH intensities per bond from
      18 compounds correlate linearly with the values calculated at MP2 and B3LYP
      levels: the corresponding HF plot is slightly curved. The new HC(Si) data fit
      these correlations adequately. In similar plots for SiH stretching intensity, the
      point for SiH2Cl2 is displaced, especially at the HF level. The lack of relation
      of nuCH or nuSiH intensity to Mulliken atomic charge points to the effect of
      varying atomic charge flux in the parameter thetamu/thetar. Anomalies associated
      with nuSiH intensities influenced by chlorine or OR substitution and previously
      explained by d(pi)-p(pi) bonding are attributed instead to charge flux variation.
      For silyl groups, deformation band intensities are roughly additive according to
      the number of such groups. However, this is not the case for the methyl symmetric
      deformation bands in methyl and dimethyl silanes.

PMID- 15582814
TI  - Detection of the site of phosphorylation in a peptide using Raman spectroscopy
      and partial least squares discriminant analysis.
AB  - Normal (non-enhanced) Raman spectroscopy is used to determine the site of
      phosphorylation on a 13-residue peptide whose sequence derives from the cellular
      protein pp60(c-src) (protein tyrosine kinase). Raman spectra of serine, threonine
      and tyrosine amino acids and their phosphorylated derivatives are used to aid in
      the interpretation of peptide spectra. The purity of the synthetic peptides are
      confirmed by mass spectroscopy. Peptide Raman measurements are performed using
      the recently reported drop-coating deposition Raman (DCDR) method, followed by
      Savistky-Golay second derivative (SGSD) pre-processing and multivariate spectral
      classification using partial least squares (PLS) discriminant analysis. Leave-one
      out training/testing results are displayed using a PLS psuedo-probability score
      plot and shown to facilitate error-free spectral determination of the site of
      phosphorylation.

PMID- 15582815
TI  - Vibrational analysis of hydroxyacetone.
AB  - In order to be able to fully understand the vibrational dynamics of
      monosaccharide sugars, we started with hydroxyacetone CH2OHCOCH3, and
      glycolaldehyde CH2OHCOH, which are among the smallest molecules that contain
      hydroxyl and carbonyl group on neighboring carbon atoms. This sterical
      configuration is characteristic for saccharides and determines their biochemical
      activity. In this work vibrational analysis of hydroxyacetone was undertaken by
      performing the normal coordinate analysis for glycolaldehyde first, and
      transferring these force constants to hydroxyacetone. The observed Raman and
      infrared bands for 90 wt.% solution of hydroxyacetone in water (acetol) were used
      as a first approximation for the bands of free hydroxyacetone. The number of
      observed Raman and infrared bands for acetol exceeds the number of calculated
      values for the most stable hydroxyacetone conformer with Cs symmetry, which
      suggests more than one conformer of hydroxyacetone in water solution. In
      particular, there are two bands both in infrared (1083 and 1057 cm(-1)) and in
      Raman spectrum (1086.5 and 1053 cm(-1)) that are assigned to the CO stretching
      mode and this is one of the indicators of several hydroxyacetone conformers in
      the solution. Additional information was obtained from low temperature Raman
      spectra: at 240 K a broad asymmetric band centered around 280 cm(-1) appears,
      suggesting a disorder in the orientation of hydroxyl groups. Glassy state forms
      at approximately 150K. The broad band at 80 cm(-1) is assigned to frozen torsions
      of hydroxymethyl groups.

PMID- 15582816
TI  - Fluctuations in absorbance observed for photoexcited ferrocene-doped poly(methyl
      methacrylate) thin films containing chloroform molecules as impurities.
AB  - The time-dependent changes in absorbance in the case of ferrocene-doped
      poly(methyl methacrylate) thin films containing chloroform molecules have been
      investigated after photoexcitation in nitrogen atmosphere. Photoexcitations have
      been made by the monochromatic light (using Xe-source and a monochromator) in the
      UV range. An increase in absorbance associated with spectacular fluctuations in
      its value, has been noticed. The nature of the variation in the fluctuations has
      been studied as a function of time (duration) of photoexcitation, photoexcitation
      wavelength and concentration of ferrocene in the film. The observed results have
      been discussed considering the role of secondary reaction after photoexcitation
      as well as the diffusion of small chemical species in the polymer matrix.

PMID- 15582817
TI  - A theoretical study of nonlinearity in heterocyclic hydrogen-bonded complexes.
AB  - Ab initio calculations are performed at the MP2/6-311++G(d,p) and DFT/B3LYP/6
      311++G(d,p) theoretical levels to obtain geometries, H-bond energies and harmonic
      infrared vibrational properties for the Cs symmetry structures of heterocyclic
      hydrogen-bonded complexes, CnHmY-HX. The H-bond lengths in DFT/B3LYP calculation
      level are in better agreement with the experimental values than the MP2 results.
      The geometry optimization are interpreted in terms of hydrogen bond nonlinearity
      represented by theta; and phi angles, once the hydrogen bond is formed among n
      electrons pairs of the heteroatom in heterocyclic and the hydrogen atom in HX.
      The hydrogen bond energy after of the zero-point vibrational energy (ZPE) and
      basis set superposition error (BSSE) corrections are overestimated at DFT/B3LYP,
      whereas the MP2 BSSE corrections are very large than corresponding DFT/B3LYP. For
      example, the BSSE corrections for the C2H4S-HNC complex are 7.60 and 0.09 kJ mol(
      1) in MP2 and DFT/B3LYP calculations levels, respectively. The new vibrational
      modes in infrared harmonic spectrum arising from complexation show several
      interesting features, especially the intermolecular stretching mode.

PMID- 15582818
TI  - Resonance Raman spectra of n-pi* singlet-triplet transition of p-benzoquinone at
      low concentrations.
AB  - A weak visible absorption spectrum of p-benzoquinone (p-BQ) in CS2 due to n-pi*
      singlet-triplet transition was measured. Using the resonance Raman (RR) effect in
      liquid-core optical fiber (LCOF), we have obtained the 514.5 nm excited RR
      spectra of p-benzoquinone near 1445 cm(-1) and have demonstrated that the new
      characteristic RR band is attributed to the symmetric C=O stretch (nu(C=O)) of n
      pi* singlet-triplet transition of p-BQ. The effect of solution concentration on
      the RR band was investigated at very low concentrations. The RR peak spreads
      toward short wavelength side with decreasing solution concentration ranging from
      10(-7) to 10(-11) mol L(-1), whereas the blue-shift isn't obvious when the
      concentration is, at single molecule level, lower than 10(-11) mol L(-1). Our
      result is useful for single molecule detection to some extent.

PMID- 15582819
TI  - Crystal growth and vibrational spectroscopic studies of the semiorganic non
      linear optical crystal--bisthiourea zinc chloride.
AB  - The semiorganic non-linear optical crystal bisthiourea zinc chloride (BTZC) was
      grown by mixed solvent slow evaporation technique. The solubilities under various
      solvents in different proportions have been studied. Vibrational spectra were
      recorded to determine the symmetries of molecular vibrations. The observed Raman
      and infrared bands were also assigned and discussed. The optical transmission
      spectral study was also carried out. The property of second harmonic generation
      of BTZC was also verified.

PMID- 15582820
TI  - Vibrational and surface-enhanced vibrational spectra of 6-nitrochrysene.
AB  - The infrared and Raman spectra of solids and thin solid films of 6-nitrochrysene,
      its electronic spectra, and resonance Raman scattering (RRS) obtained with UV
      laser excitation at 325 nm are reported. The vibrational assignment is supported
      by ab initio computations at the B3LYP/6-311G(d, p) level of theory. The
      molecular organization in nanometric films evaporated onto smooth metal surfaces
      of silver and copper was probed using reflection-absorption infrared spectroscopy
      (RAIRS). The results of the surface-enhanced Raman scattering (SERS) and surface
      enhanced infrared absorption (SEIRA) obtained from nanometric films evaporated
      onto silver island films are also discussed. It was found that the molecule
      efficiently interacts with silver island film surfaces, and that the interaction
      leads to extensive photochemical reaction at the metal surface under laser
      illumination.

PMID- 15582821
TI  - Infrared spectroscopy of organoclays synthesized with the surfactant
      octadecyltrimethylammonium bromide.
AB  - Infrared (IR) spectroscopy using a smart endurance single bounce diamond
      attenuated total reflection (ATR) cell has been used to study the changes in the
      spectra of the surfactant octadecyltrimethylammonium (ODTMA) bromide upon
      intercalation into a sodium montmorillonite. The wavenumbers of bands attributed
      to CH-stretching and CH-bending vibrations, in general, decrease as the
      concentration of the surfactant measured in terms of the cation exchange capacity
      (CEC) up to 1.0 CEC. After this point, the bands increase approaching a value the
      same as that of the surfactant. Significant changes occur in the HCH deformation
      modes of the methyl groups of the surfactant. These changes are attributed to the
      methyl groups locking into the siloxane (SiO) surface of the montmorillonite.
      Such a concept is supported by changes in the SiO-stretching bands of the
      montmorillonite siloxane surface.

PMID- 15582822
TI  - Spectroscopic studies of the interaction between crown ethers and organic
      nitriles.
AB  - The interaction of 18-crown-6 (18C6), diaza-18-crown-6 (DA18C6), and dithia-18
      crown-6 (DT18C6) with acetonitrile and malononitrile was investigated using
      infrared spectroscopy, 1H and 13C NMR spectroscopy, and molecular modeling. The
      interaction between 18C6 and the nitriles involves hydrogen bonding between the
      CH3/CH2 protons of the nitriles and the ether oxygens of the crown. In contrast,
      the interaction between the organic nitriles and DA18C6 involves the nitrogen of
      the nitrile group and the N-H groups of the crown. Due to the bulkiness of the
      sulfur atoms of DT18C6, no interaction was observed to occur between acetonitrile
      and the crown.

PMID- 15582823
TI  - Absorption spectroscopic investigations involving 4f-4f transitions to explore
      the kinetics of complexation of Zn(II) with Pr(III)-glutathione complex.
AB  - The kinetics of complexation of Zn(II) with Pr2(GSH)2.(H2O)4 1 (GSH-glutathione)
      to form Pr2(GSH)2Zn(H2O)6 complex 2 has been investigated at 30 degrees C by
      following the changes in the intensity (absorbance, molar absorptivity) and
      intensity (oscillator strength P and Judd-Ofelt-T(lambda) intensity) parameters
      in equimolar DMF-Water. In order to support kinetics data, the complex 1 and 2
      have been synthesized and characterized by elemental analysis, IR and 1H NMR
      spectral analysis. Molecular weights of 1 and 2 determined by ebullioscopic and
      cryoscopic methods and preliminary molecular modeling experiments have helped in
      proposing most probable structures for 1 and 2. Kinetics showed first order
      dependence, in terms of concentration of Zn(II) and complex 1, on the rate of
      formation of complex 2. Generally, hypersensitive transitions (the transitions
      obeying /DeltaJ/ selection rules) were used in spectra-structure correlation
      studies. We have used the four 4f-4f transitions of Pr(III), which do not obey
      selection rules, yet are substantially sensitive to coordination changes, for
      kinetic study. The rate constants evaluated from individual 4f-4f bands are quite
      close hence supporting our observations on ligand mediated
      pseudohypersensitivity.

PMID- 15582826
TI  - Phenobarbital: a drug for the 21st century?

PMID- 15582827
TI  - Neuropsychological outcome following focal cortical removal for intractable
      epilepsy in children.
AB  - In children, surgery for epilepsy has been recognized as a viable treatment
      option since publication of S. Davidson and M.A. Falconer's outcome study in 1975
      [Lancet North Am Ed 5:1260-3], which demonstrated that medical outcome of
      children who underwent anterior temporal lobectomy paralleled that of adults.
      Pediatric surgical programs and the literature on medical outcome have grown
      considerably since that time, with surgery being offered to children with
      temporal but also extratemporal epilepsy foci. Comparatively little work has been
      conducted in the area of neuropsychological outcome. This article outlines
      differences in adult and pediatric outcome studies, reviews the literature on the
      intellectual and memory outcome in children, and discusses shortcomings of the
      pediatric outcome research conducted to date.

PMID- 15582828
TI  - Traumatic events and posttraumatic stress disorder in patients with psychogenic
      nonepileptic seizures: a critical review.
AB  - Although video-EEG monitoring has revolutionized the diagnosis of psychogenic
      nonepileptic seizure (PNES), the etiology of this condition remains poorly
      understood. This article is a critical review of studies on the prevalence of
      traumatic events, abuse, and/or posttraumatic stress disorder (PTSD) in patients
      with PNES. Searches carried out on MEDLINE (1966-2004) and Web of Science (1945
      2004) identified 17 relevant studies. PNES samples showed very high rates of
      trauma (44-100%) and abuse (23-77%), which were 15-40% higher than those found in
      control groups. This suggests that traumatic experiences may be a potential risk
      factor for PNES. PNES samples also showed a higher prevalence of PTSD than
      control groups, raising the possibility that PNES may arise as a clinical
      expression of a hypothetical PTSD subtype the core symptoms of which are
      dissociative. Methodological limitations do not permit the confirmation of these
      hypotheses. Stronger research designs are needed, such as prospective and case
      control studies in both hospital and community settings.

PMID- 15582829
TI  - The interictal dysphoric disorder: recognition, pathogenesis, and treatment of
      the major psychiatric disorder of epilepsy.
AB  - The unawareness of psychiatrists about the importance of epilepsy dates back half
      a century, when epilepsy became considered an ordinary neurologic disorder.
      Epileptic seizures, however, can be provoked in every human being. Epilepsy is an
      extraordinary disorder that, beyond its well-known neurologic complexities, tends
      to become complicated with a wide range of specific psychiatric changes; they
      occur on the establishment of a temporal-limbic focus of intermittent excessive
      neuronal excitatory activity that produces increasingly inhibitory responses.
      These changes are distinct from those related to the two major psychiatric
      spheres for which a genetic basis is established, i.e., the manic-depressive and
      schizophrenic disorders, and represent a genetic sphere of its own. Apart from
      more subtle personality changes and the serious late complications of interictal
      psychoses and suicidal episodes, the key psychiatric syndrome associated with
      epilepsy consists of the interictal dysphoric disorder, with its characteristic
      intermittent and pleomorphic symptomatology. This disorder was clearly identified
      about a century ago by Kraepelin, when he established a comprehensive basis for
      the modern classification of the psychiatric disorders, at a time when epilepsy
      represented an area of major interest to psychiatrists. A practical method of
      recognizing the dysphoric disorder is reported. The disorder tends to be very
      treatable by combining psychotropic (chiefly antidepressant) with antiepileptic
      medication. The variations in treatment approach required are discussed and
      illustrated by representative case studies. Psychiatrists must become familiar
      with the psychiatric aspects of epilepsy to be able to assist the neurologists
      who focus on the neural complexities of the illness. They also must become able
      to recognize, among their own patients, the presence of a subictal dysphoric
      disorder that requires the same treatment as the interictal dysphoric disorder;
      combined treatment with antidepressant and antiepileptic medication is likewise
      indicated for the premenstrual dysphoric disorder, a condition that appears to
      belong to the spectrum of epilepsy-related psychiatric disorders. Furthermore,
      they must learn how an ignored population in their care, epilepsy patients
      confined to state hospitals, can be properly treated. Of particular importance is
      the need for psychiatrists to become familiar with the role of the paroxysmal
      affects in the general human condition, with their basic conflict to be
      intermittently angry and irascible yet otherwise good-natured, helpful, and
      religious--a conflict that tends to be particularly accentuated among patients
      with the "Sacred Disease."

PMID- 15582830
TI  - Assessment of adverse events and quality of life in epilepsy: design of a new
      community-based trial.
AB  - Improving health-related quality of life (HRQOL) has become recognized as an
      essential component of treating patients with epilepsy. In recent years, several
      rating scales have been developed that focus on both common adverse effects and
      various aspects of HRQOL that are more relevant to this patient population.
      Increasingly, such assessments are being incorporated into clinical trials, as it
      becomes clear that improvements in overall quality of life are an important
      feature of drug therapy. Here we present the design of a large, community-based
      trial evaluating the effects of switching from immediate-release carbamazepine to
      twice-daily, beaded, extended-release carbamazepine (Carbatrol). As this trial
      involves switching formulations of the same compound, we expect to find only
      small differences in efficacy but significant differences in tolerability and
      quality-of-life measures. To identify appropriate instruments that could measure
      these factors, here we review several epilepsy-specific scales used to monitor
      adverse events and HRQOL and discuss their potential utility in the context of
      the proposed trial.

PMID- 15582831
TI  - Acute effect of an extract of Ambrosia paniculata (Willd.) O. E. Schultz
      (mugwort) in several models of experimental epilepsy.
AB  - The acute effect of Ambrosia paniculata was studied in several animal models of
      epilepsy. Intraperitoneal injections (0.01 mL/g body wt) of a decoction of the
      dry leaves significantly enhanced the latency to the first convulsion and
      survival time in mice injected with picrotoxin (7 mg/kg) or isoniazid (210
      mg/kg). Epileptic spikes were induced by topical application of penicillin
      through a glass electrode filled with a penicillin-agar-saline mixture and
      recorded in sensorimotor and occipital cortices, in rats immobilized with d
      tubocurarine. The plant decoction reduced significantly the spike amplitude in
      both sites. The mentioned effects were elicited at doses that also reduced
      general motor activity (Irwin test) and exploratory behavior. The decoctions were
      not effective against electroshock-induced convulsions in mice. The convulsions
      induced by isoniazid, picrotoxin, and penicillin differed from those induced by
      electroshock implicating selective disruption of GABAergic neurotransmission. The
      results suggest that A. paniculata, like several conventional antiepileptic
      drugs, might act by enhancing GABAergic neurotransmission, a hypothesis that
      requires further demonstration. These results explain and justify the traditional
      use of the plant in epilepsy.

PMID- 15582832
TI  - Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced
      seizures and mortality.
AB  - Cocaine abuse may lead to overdose (related to seizures and/or status
      epilepticus) and to diseases (schizophrenia, depression, and anxiety). This work
      was designed to study the influence of drugs used to treat psychopathologies
      associated with cocaine abuse on cocaine-induced seizures and mortality in mice.
      Fluoxetine (10, 20, 40 mg/kg), imipramine and buspirone (5, 10 mg/kg), pimozide
      (10, 20 mg/kg), lithium (56.3, 112.5 mg/kg), and naltrexone (25, 50 mg/kg) were
      administered intraperitoneally, 30 minutes prior to cocaine (90 mg/kg, ip). The
      animals were observed (30 minutes) to determine: latency to first seizure, number
      of seizures, and number of deaths after cocaine overdose. Fluoxetine, imipramine,
      buspirone, and pimozide had pro- or anticonvulsant effects depending on the dose.
      Smaller doses protected and higher doses increased cocaine-induced seizures
      and/or mortality. Naltrexone worsened and lithium protected against seizures.
      Thus, these results suggest that caution should be taken in the selection of
      pharmacotherapy and dosages for patients with cocaine addiction because of the
      possibility of potentiating cocaine toxicity.

PMID- 15582833
TI  - Effects of antiepileptic drugs on working memory as assessed by spatial
      alternation performance in rats.
AB  - Patients with epilepsy can have impaired cognitive abilities. Many factors
      contribute to this impairment, including the adverse effects of antiepileptic
      drugs (AEDs). However, there are few systematic data on the effects of AEDs on
      specific cognitive domains, such as working memory. The purpose of the present
      study was to evaluate the effects of AEDs on working memory as measured by
      delayed spatial alternation behavior in nonepileptic rats. The GABA-related AEDs
      triazolam and phenobarbital significantly disrupted performance, whereas
      tiagabine, valproate, and gabapentin did not. The sodium channel blockers
      carbamazepine and topiramate produced modest but significant disruption of
      performance, whereas the effects of lamotrigine were not significant and
      phenytoin produced a modest but significant improvement in performance but at
      doses that abolished responding in some animals. Levetiracetam had no effect on
      working memory. In contrast, ethosuximide significantly disrupted working memory.
      The disruptions produced by triazolam and phenobarbital were similar in magnitude
      to the effects of the muscarinic antagonist scopolamine. The present results
      indicate that AEDs can disrupt working memory, but there are differences among
      AEDs in the magnitude of the disruption that do not appear to be correlated with
      mechanism of action.

PMID- 15582834
TI  - Correlation analysis between anticonvulsant ED50 values of antiepileptic drugs in
      mice and rats and their therapeutic doses and plasma levels.
AB  - OBJECTIVE: Although there are several animal models of epilepsy, the
      extrapolation of antiepileptic drug (AEDs) performance to epileptic patients from
      anticonvulsant activity results in animals is not straightforward. Consequently,
      the aim of this work was to perform a correlation analysis between therapeutic
      daily doses (D) and average steady-state plasma concentrations (Css,av) of AEDs
      and their activity in common anticonvulsant animal models. METHODS: AED activity
      in anticonvulsant animal models was expressed as maximal electroshock seizure
      (MES) test ED50 values in mice and rats and ED50 values in audiogenic seizure
      susceptible mice (AGS ED50). Data were examined, by use of linear and logarithmic
      approaches, for an association between Css,av (mg/L or micromol/L) and D (mg or
      mmol) for each AED in epileptic patients as the dependent variable (Y) and its
      MES ED50 in mice and rats and AGS ED50 in mice (mg/kg or micromol/kg) as the
      independent variable (X). RESULTS: Linear correlation analyses between Css,av
      (mg/L) and ED50 (mg/kg) for 11 AEDs gave the following correlation coefficients
      (R2): 0.68 (mice, MES); 0.73 (rat, MES); 0.64 (AGS). Switching the units from
      milligrams to micromoles improved the correlation significantly and gave the
      following R2 values: 0.88 (mice, MES); 0.90 (rat, MES); 0.76 (AGS). The linear
      correlation between Css,av and ED50 was better than that between D and ED50.
      CONCLUSIONS: The results of this analysis suggest that the relationship between
      Css,av and ED50 is useful in predicting target concentration ranges in humans.
      The Y intercepts of the Css,av-versus-ED50 and D-versus- ED50 plots were similar
      in all three animal models and ranged between 12 and 17 mg/L and between 570 and
      890 mg, respectively, indicating that for all AEDs analyzed except valproic acid
      and ethosuximide, the therapeutic plasma concentration is in the range 10-20
      mg/L.

PMID- 15582835
TI  - Cognitive impairment following status epilepticus and recurrent seizures during
      early development: support for the "two-hit hypothesis".
AB  - Prolonged seizures in immature rats result in minimal behavioral consequences
      when the animals are studied later in life. Likewise, early-onset seizures are
      associated with minimal morphological changes. However, it is known that seizures
      early in life result in changes in the brain that make it more vulnerable to
      subsequent seizure-induced injury (the so-called two-hit hypothesis). Whether
      this heightened vulnerability occurs immediately after the first seizure is not
      known. In this study, immature rats were exposed to status epilepticus (SE)
      followed by a series of 25 flurothyl-induced seizures, SE alone, 25 flurothyl
      induced seizures alone, or no seizures. Rats exposed to SE and flurothyl seizures
      performed significantly poorer in the water maze 2 weeks following the last
      seizure compared with the other groups. No histological lesions were seen in any
      of the four groups. This study suggests that SE renders the immature brain
      vulnerable to further seizure-induced injury and this enhanced vulnerability
      occurs very quickly after the SE.

PMID- 15582836
TI  - Levetiracetam for people with mental retardation and refractory epilepsy.
AB  - Levetiracetam (LEV) is a novel antiepileptic drug (AED) with efficacy against a
      wide range of seizures types. The aim of this observational study was to assess
      its effectiveness in patients with mental retardation and refractory epilepsy.
      Sixty-four patients were started on adjunctive LEV after a 3-month baseline. LEV
      was initially dosed at 250 mg daily and increased by 250 mg every 2 weeks
      thereafter according to clinical response. Caregivers rated the patient's sleep,
      appetite, alertness, and behavior as poor (1), reasonable (2), or good (3) at
      each clinic visit. Patients were reviewed until one of four endpoints was
      reached: seizure freedom for at least 6 months, > or = 50% reduction in seizure
      frequency (responder) over a 6-month period, <50% reduction in seizure frequency
      (marginal effect) over a 6-month period, or LEV withdrawal due to lack of
      efficacy, adverse effects, or both. Twenty-four (38%) patients became seizure
      free, 10 of whom were controlled on LEV 250 mg twice daily. An additional 18
      (28%) patients were classified as responders, and 8 (12%) reported only marginal
      benefit from adjunctive LEV. Fourteen (22%) patients discontinued LEV (6
      worsening seizures, 1 lack of efficacy, 7 adverse effects). Caregivers rated
      combined sleep, appetite, alertness, and behavior scores as "improved" at the end
      of follow-up (P<0.001). LEV improved seizure control in the majority of patients
      with mental retardation and may also have enhanced their quality of life.

PMID- 15582837
TI  - Epilepsy and insurance in the UK: an exploratory survey of the experiences of
      people with epilepsy.
AB  - We investigated problems in obtaining insurance as reported by people with
      epilepsy who were members of a major United Kingdom patient organisation.
      Information was collected via questionnaires mailed to a random sample of the
      membership, 347 of whom replied. Overall, 62% of respondents reported
      experiencing a problem obtaining insurance coverage (increased premiums,
      restricted coverage, or outright refusal). Thirty-six percent of respondents
      reported having been refused one or more types of insurance on the grounds of
      their epilepsy. Although the low response rate to the study represents an
      important source of bias, extrapolation from our figures suggests a problem
      prevalence rate of at least 10%. Adoption of an evidence-based and standardised
      approach to informing assessments of risk is vital if insurance companies are to
      provide fair and reasonable terms for insurance coverage to their clients with
      epilepsy.

PMID- 15582838
TI  - Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy
      volunteers.
AB  - We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin
      (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy
      volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and
      cognitive testing were performed at baseline and after 12 weeks of treatment. For
      each subject and measure, test-retest Z scores were calculated from regression
      equations derived from 73 healthy controls. Twenty-six subjects completed the
      study. Both the OXC and PHT groups had significant slowing of the EEG peak
      frequency and increased relative theta and delta power. Differences between AEDs
      (antiepileptic drugs) were not significant. Significant cognitive effects were
      seen on 5 of 20 measures, primarily measures of motor speed and reaction time.
      Again, there were no significant differences between AEDs. The only significant
      difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small
      sample size may have contributed to the lack of significant differences between
      AEDs.

PMID- 15582839
TI  - Development of cognitive functions in children with rolandic epilepsy.
AB  - An initial investigation of cognitive functions in 32 children, aged 7 to 15
      years, with rolandic epilepsy (RE), using an extensive test battery, was followed
      2.5 to 3 years later by a second assessment of 26 of these children, using the
      same technique. The initial investigation reported cognitive deficits in memory
      and learning of auditory-verbal material together with executive functions
      compared with controls. At the second assessment, the ability for immediate
      memory, memory and learning of visuospatial as well as auditory-verbal material
      and delayed recall was the same in the RE group as in the control group. On one
      of the tests measuring executive functions, Verbal Fluency, the RE group scored
      significantly lower than controls. With respect to reading and writing ability,
      the children with RE had some difficulty with word comprehension. Nonverbal
      reasoning was the same in the two groups, as was general IQ. In conclusion, the
      children with RE did not present any major cognitive difficulties when a mean of
      approximately 5 years had passed since onset of the typical syndrome, and at a
      time when most of them were seizure-free. Maturational factors apparently are of
      importance to the course of RE.

PMID- 15582840
TI  - Personality testing and epilepsy: comparison of two MMPI-2 correction procedures.
AB  - The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is widely used for
      assessing psychopathology. However, its reliability in people with neurologic
      disease has been questioned. This concern is especially true for epilepsy, a
      disease with symptoms, i.e., seizures, that frequently include experiences likely
      to suggest psychopathology. Correction procedures, in which select items are
      removed and the test is rescored, may improve MMPI-2 specificity. The MMPI-2 was
      administered to 27 subjects with epilepsy, and the results were compared before
      and after application of three correction procedures: rational, statistical, and
      combined. The statistical correction resulted in clinically significant T-score
      changes (> or = 5 points) in two MMPI-2 clinical scales, while a combined
      correction procedure produced clinically significant changes in three scales. In
      the subgroup of patients with intractable epilepsy, two noncorrected scale T
      scores > or = 65 fell to the normal range with both the statistical and combined
      procedures. These results suggest cautious interpretation of standard MMPI-2
      scores in patients with epilepsy.

PMID- 15582841
TI  - Relationship between information processing speed in temporal lobe epilepsy and
      white matter volume.
AB  - Abnormalities in white matter have been linked to processing speed impairment in
      clinical populations (e.g., multiple sclerosis, closed head injury). Recent
      studies indicate the presence of significant reduction in cerebral white matter
      volume in some patients with chronic temporal lobe epilepsy (TLE). The objective
      of this study was to examine the relationship between white matter volume and
      processing speed and performance efficiency on the Sternberg Memory Scanning Test
      (SMST). The study groups included TLE subjects with white matter volume reduction
      (n=13), TLE subjects with normal white matter volume (n=14), and healthy controls
      (n=18). The groups did not differ in total cerebral gray matter volume. Compared
      with the controls, the reduced white matter volume TLE group exhibited a
      significantly steeper slope on the SMST. This was characterized by a
      disproportionate increase in reaction time with increased processing demands (set
      size), particularly for negative probe trials. In contrast, no significant
      differences on the SMST were evident between controls and the normal white matter
      volume TLE group. These findings suggest the presence of information processing
      speed and efficiency impairment in TLE and its relationship with white matter
      volume integrity.

PMID- 15582842
TI  - Learning disability: occurrence and long-term consequences in childhood-onset
      epilepsy.
AB  - This study analyzed the occurrence of learning disability (LD) in adults with
      childhood-onset epilepsy and the impact of LD on medical and social outcome. Any
      LD occurred in 76%: in 57% of mentally normal (IQ>85), in 67% of mentally near
      normal (IQ=71-85), and, self-evidently, in all mentally retarded (IQ<71) adults.
      Half of the patients (51%) with LD had mental retardation. In multivariate
      analysis, mental retardation and subsequent LD were predicted by occurrence of
      cerebral palsy (odds ratio [OR]=3.83; 95% confidence interval [CI]=1.77-8.28,
      P=0.0006), onset of epilepsy before the age of 6 years (OR=3.63, 95% CI=1.57
      8.42, P=0.0026), and poor early effect of drug therapy (OR=2.78, 95% CI=1.43
      5.39, P=0.0025). Among mentally normal or near-normal subjects, a symptomatic
      etiology of epilepsy was the only predictor (OR=7.72, 95% CI=3.02-19.76). The
      degree of LD significantly affected medical, social, and educational long-term
      outcomes.

PMID- 15582843
TI  - Do patients with epilepsy believe they need specific dietary restrictions?
AB  - PURPOSE: Almost 1000 years ago, Avicenna, the great Iranian scientist,
      recommended that patients with epilepsy should avoid some foods. In the present
      study we attempted to identify beliefs and experiences of families with epileptic
      children with respect to the need for specific dietary restrictions in these
      patients. METHODS: A cross-sectional study was carried out using a questionnaire
      at the outpatient clinic of Motahary in Shiraz, Iran, in 2004. Patients with
      unprovoked seizures and abnormal electroencephalograms who were under follow-up
      for at least 2 months were included in the study. RESULTS: In total 125 families
      participated. Of these, 55.2% believed there was a relationship between specific
      foods and the occurrence of seizures. Personal experience with seizures after
      consumption of specific foods was reported by 31.2% of the families. Dairy
      products, sour foods, fruits, and vegetables were the most common foods reported
      to be responsible. CONCLUSION: It was clearly observed that parents desire to
      know if their children with epilepsy require dietary restrictions and, hence, try
      to collect information from different and sometimes unreliable sources. It would
      be invaluable to consider the experience of families caring for epileptic
      children when evaluating the relationship between consumption of specific foods
      and seizures in future studies. This relationship may be due to a food-disease or
      food-drug interaction.

PMID- 15582844
TI  - Neuropsychological change following gamma knife surgery in patients with left
      temporal lobe epilepsy: a review of three cases.
AB  - Gamma knife surgery (GKS) is a radiation procedure recently used in the treatment
      of temporal lobe epilepsy (TLE). Preliminary studies have shown significant
      seizure reductions in patients 8-26 months postprocedure; however, little is
      known about the effect of GKS on cognitive functioning in TLE. We report
      neuropsychological data on three patients with left TLE and MRI evidence of
      hippocampal sclerosis who underwent GKS. Two models for assessing cognitive
      change, reliable change indices and regression-based norms for change, were used
      to measure preoperative versus 13- to 27-month postoperative cognitive change.
      Results revealed a significantly long delayed verbal memory decline on one
      measure following GKS. No patient declined on measures of IQ, visual memory, or
      language. Radiation-induced edema was present at the time of testing in all three
      patients, which may have affected verbal memory performance. While preliminary,
      these data suggest that GKS offers a less invasive option to anterior temporal
      lobectomy, but may produce neuropsychological changes similar to those produced
      by left anterior temperol lobectomy up to 2 years post-GKS treatment.

PMID- 15582845
TI  - Anxiety and depression in children with epilepsy and their mothers.
AB  - OBJECTIVE: Children with epilepsy have high rates of depression and anxiety. The
      majority of studies concentrate on the children with epilepsy, but the emotional
      impact of epilepsy on family members is of clinical concern. In this cross
      sectional study we aimed to examine the association between epilepsy in childhood
      and adolescence, and anxiety and depression in these patients and their mothers.
      METHODS: We studied 35 children and adolescents with seizures (age range, 7-19
      years), 35 gender-matched healthy controls (age range, 8-17) who did not have any
      chronic medical illness, and mothers of these individuals (n=70) in a cross
      sectional analysis. We administered the Kovac Child Depression Inventory (CDI)
      and State-Trait Anxiety Inventory for Children (STAIc) to the children. We
      administered the Beck Depression Inventory (BDI) and State-Trait Anxiety
      Inventory (STAI) to the mothers of these children. Pearson correlations were used
      to analyze dependence between variables, and Student's t test was used to compare
      mean values between test scores. RESULTS: Patients with epilepsy had higher CDI
      scores (mean+/-SD, 12.48+/-6.35) than controls (9.31+/-5.11) (P<0.05), whereas
      the STAIc scores did not differ between cases (34.03+/-8.29) and controls
      (35.20+/-6.23) (P<0.05). Mothers of children with epilepsy did not have more
      depression or anxiety symptoms than mothers of children without epilepsy as
      measured by BDI and STAI scores (P>0.05). There was no correlation between
      mothers' scores and patients' or controls' scores. CONCLUSIONS: These results
      support findings from previous studies that children and adolescents with
      epilepsy have a higher frequency of depressive but not anxiety symptoms than the
      general population of healthy children and that this is independent of their
      mothers' symptoms.

PMID- 15582846
TI  - Developing a measure to assess attitudes toward epilepsy in the US population.
AB  - The aim of this study was to develop an instrument to measure the US public's
      attitudes toward people with epilepsy and to assess the initial reliability and
      validity of the instrument. A 46-item attitudinal instrument was developed and
      tested using a proportional, stratified, national, random-digit dial household
      telephone survey of adults aged > or = 18 (n=758). Exploratory factor analyses
      revealed four underlying constructs that accounted for 34.4% of the variance in
      the factor analysis: negative stereotypes (alpha=0.73); risk and safety concerns
      (alpha=0.85); work and role expectations (alpha=0.76); and personal fear and
      social avoidance (alpha=0.79). Knowledge was also assessed; participants with
      less knowledge about epilepsy had more negative attitudes. The results of these
      analyses provided evidence for reliability and construct validity of the
      instrument. Additional tests of the reliability, validity, and factor structure
      of the scales are necessary to refine the instrument.

PMID- 15582847
TI  - Determinants of quality of life in epilepsy.
AB  - Although depression is associated with diminished quality of life (QOL) in
      epilepsy patients, the relative contributions of epilepsy-specific concerns, as
      well as clinical and cognitive variables of QOL, have not been simultaneously
      investigated. A comprehensive neuropsychological test battery including the Beck
      Depression Inventory (BDI), Epilepsy Foundation of America's (EFA) Concerns
      Index, MMPI-2, QOLIE-89, WAIS-III, and Selective Reminding was administered to
      115 epilepsy surgery candidates with normal Full Scale IQs. Linear regression
      analyses were performed to identify significant predictor combinations of QOLIE
      89 total score. Regression analysis demonstrated that depressive symptomatology,
      whether reflected by the BDI (R2=0.45) or Depression scale of the MMPI-2
      (R2=0.36), was a robust individual QOL predictor. Seizure Worry from the EFA
      Concerns Index was nearly as effective as the BDI in predicting QOLIE-89
      (R2=0.42). When the BDI and EFA Concerns Index were combined into the same
      regression, both factors continued to contribute significantly to the QOLIE-89
      total score, with both variables accounting for 61% of the variance. Although
      patients who developed their seizures at an older age had poorer QOL and patients
      with higher educational levels reported higher QOL, neither factor was related to
      QOL after accounting for the effects of psychological variables and epilepsy
      related concerns. Although quality of life has multiple determinants, symptoms of
      depression and seizure worry are the most important factors affecting QOL in
      patients with intractable epilepsy.

PMID- 15582848
TI  - Evidence of memory impairment in asymptomatic individuals with hippocampal
      atrophy.
AB  - Our objective was to investigate if MRI-determined hippocampal atrophy (HA) is
      associated with memory deficits independent of seizure frequency. We studied
      three groups of individuals: (1) 10 asymptomatic first-degree relatives of
      patients with familial mesial temporal lobe epilepsy (FMTLE), all of them with
      HA; (2) 14 patients with benign FMTLE, 9 with HA, and 5 with normal hippocampal
      volumes; and (3) 16 patients with refractory FMTLE, all but one with HA. HA was
      associated with lower scores on general memory (P=0.015), verbal memory
      (P=0.020), and delayed recall (P=0.028), even in those with no or few seizures in
      life. General linear model analyses showed that the interaction between seizure
      outcome and HA was associated with worse verbal memory (P=0.029), visual memory
      (P=0.022), and delayed recall (P=0.039) as compared with each of these factors
      independently. Our findings suggest that seizures and HA are independently
      associated with memory impairment.

PMID- 15582849
TI  - Which factors may play a pivotal role on determining the type of psychiatric
      disorder in children and adolescents with epilepsy?
AB  - Physicians have become aware of the high prevalence of psychiatric disorders
      (PDs) in children and adolescents with epilepsy; however, there are many
      controversies as to which factors may have an important role in the different
      types of PD. This study was designed to assess the main PD; verify the age of
      onset compared with the age of diagnosis of the PD; and determine which factors
      may be correlated with the type of PD described. For this purpose, a
      multidisciplinary team evaluated children and adolescents (4-18 years) with
      epilepsy and analyzed patient-related factors such as age (grouped according to
      Piaget's cognitive scale: <6 years, 7-13 years, >13 years), sex, family history
      of PDs, and cognitive status. With respect to epilepsy features, we considered
      age of onset, duration, seizure control at the time of psychiatric evaluation,
      refractoriness, antiepileptic drugs (mono- vs polytherapy), seizure type
      (generalized vs focal), and epilepsy type (idiopathic vs symptomatic/probably
      symptomatic). Depression occurred in 36.4% and attention-deficit hyperactivity
      disorder (ADHD) in 29.1%, these being the most frequent PDs in this series. Focal
      epilepsy was significantly more frequent in children and adolescents with PDs. As
      to the type of PD, age was an important factor, with a predominance of ADHD in
      children and depression in adolescents (P<0.0001). Family history was
      contributory for depression, but not for others PDs (P<0.0001). Depression
      remained underdiagnosed and untreated for a longer period. Impact of early
      diagnosis and treatment remains unknown.

PMID- 15582850
TI  - Therapeutic equivalency of generic antiepileptic drugs: results of a survey.
AB  - Controversy persists whether generic antiepileptic drugs (AEDs) are
      interchangeable with brand name drugs with respect to efficacy and adverse
      events. Three hundred and one neurologists responded to a survey regarding
      generic AEDs mailed to 6420 neurologists, for an overall response rate of 4.7%.
      One hundred and ninety-six (67.8%) neurologists reported breakthrough seizures
      after a switch from a brand name to generic AED; 93 (32.2%) did not. One hundred
      and sixty-three neurologists (56%) reported increased side effects in their
      patients after a switch from a brand name to generic AED; 128 (44%) did not.
      Fifty-two (18.4%) neurologists agreed that the Food and Drug Administration
      standards for AED bioavailability are sufficiently narrow; 231 (81.6%) did not.

PMID- 15582851
TI  - Attitudes of Brazilian psychiatrists toward people with epilepsy.
AB  - The purpose of this survey was to evaluate the experience of Brazilian
      psychiatrists in treatment, formal training, attitudes, and knowledge with
      respect to epilepsy (and associated mental disorders). One hundred fifty-seven
      Brazilian psychiatrists completed a specially developed questionnaire. Most (95%)
      had previously treated patients with epilepsy and mental disorders. About one
      third (35%) admitted a lack of any formal training in epilepsy, and only 46%
      confirmed having received some formal training in mental disorders related to
      epilepsy. Eighty percent were dissatisfied with their knowledge. Three knowledge
      based questions were answered correctly by only 10%. Almost half (48%) admitted
      that among psychiatrists, prejudice exists toward patients with epilepsy.
      Difficulties with treatment (50%) and lack of knowledge of epilepsy (50%) were
      considered the main causes of such prejudice. These data indicate an urgent need
      for improvement in education on epilepsy and associated mental disorders, as well
      as inclusion of formal epilepsy training in psychiatry residency programs.

PMID- 15582852
TI  - Nonepileptic seizures following general anesthetics: a report of five cases.
AB  - Five patients who developed seizures following a general anesthetic are
      described. It is not possible to determine retrospectively whether or not the
      initial attacks were definitely epileptic, but these patients all subsequently
      received a diagnosis of psychological nonepileptic convulsions/seizures (also
      known as pseudoseizures, psychogenic nonepileptic seizures, and nonepileptic
      attack disorder) established by video/EEG telemetry or ictal EEG recordings. In
      two cases there was evidence of concurrent epilepsy. We suggest that nonepileptic
      seizures may develop following postanesthetic seizures and that a psychogenic
      basis for seizures occurring after general anesthetics needs to be considered.

PMID- 15582853
TI  - Lesion lateralization in patients with epilepsy and precocious destructive
      insults.
AB  - Destructive brain lesions that occur early in development are often unilateral or
      asymmetric. We analyzed the lateralization of lesions among a previously reported
      series of 51 patients with three kinds of destructive lesions based on their
      topography: specific arterial territory (AT), arterial borderzone territory
      (Bdz), hemispheric (H). Five patients (all from group Bdz) had bilateral
      nonlateralizing lesions. The distributions of left- and right-sided lesions were
      distinct among the groups (P=0.014): in group H, all patients except one
      presented with right-sided lesions (89%); in group Bdz, left-sided lesions (53%)
      were more frequent than right-sided lesions (17.7%); in group AT, left- and right
      sided lesions were more equally distributed (56 and 44%). Our study suggests that
      there is a trend toward lesion lateralization among patients with different
      patterns of precocious destructive lesions. Differences in cerebral maturation
      and vulnerability between the hemispheres is a possible factor explaining lesion
      lateralization in early life insults.

PMID- 15582854
TI  - Monotherapy treatment of bipolar disorder with levetiracetam.
AB  - Bipolar patients with early-onset, comorbid substance abuse, rapid cycling, and
      mixed episodes are difficult to treat and frequently require rational
      polypharmacy. When polypharmacy is unsuccessful, the clinician must consider the
      off-label use of newer psychotropics. Levetiracetam is a novel anticonvulsant
      with antikindling, inhibitory, and neuroprotective properties that is effective
      in an animal model of mania. This case report describes a patient with treatment
      resistant rapid cycling bipolar disorder who failed 15 psychotropics,
      individually or in various combinations (maximum of 6), but ultimately responded
      to levetiracetam monotherapy and remained without bipolar features during 1 year
      of maintenance treatment, excluding 1 week during which the patient was medicine
      noncompliant. Further, methylphenidate used to treat comorbid attention deficit
      disorder did not precipitate manic features. Levetiracetam should be further
      studied for its potential use in the treatment of bipolar disorders.

PMID- 15582855
TI  - New-onset mesial temporal lobe epilepsy in a 90-year-old: clinical and EEG
      features.
AB  - Although there is a peak in the incidence of epilepsy in the elderly compared
      with the general population, complex partial seizures represent less than 15% of
      the seizure types reported. We report on a 92-year-old woman with a 2-year
      history of daily complex partial seizures. Prolonged video/EEG recording showed
      bilateral anterior mesial temporal interictal spikes, which predominated on the
      left, and two typical seizures arising from the left temporal area. Cranial MRI
      scanning showed multiple lacunar infarcts without temporal lobe involvement or
      mesial temporal atrophy. Our case appears to be oldest patient in the literature
      with newly diagnosed mesial temporal lobe epilepsy confirmed by video/EEG
      recording.

PMID- 15582856
TI  - Effects of zonisamide on the electroencephalogram of a patient with juvenile
      myoclonic epilepsy.
AB  - Zonisamide, a newer antiepileptic drug (AED) with multiple mechanisms of action,
      has been increasingly used in patients with generalized epilepsies. This case
      study focuses on the effects of zonisamide on the EEG of a patient with juvenile
      myoclonic epilepsy. The patient had complete resolution of myoclonic jerks and
      absence and generalized seizures on introduction and titration of therapy with
      zonisamide; his EEG showed almost complete resolution of generalized spike and
      wave discharges and electrographic absence seizures. This case report suggests
      that zonisamide may be effective in the treatment of medication-resistant
      idiopathic generalized epilepsy and that it may lead to a significant improvement
      of the EEG.

PMID- 15582857
TI  - Bias and accuracy in close relationships: an integrative review.
AB  - Intimates typically are positively biased in their relationship evaluations.
      Given this fact, how can intimates regulate their esteem needs about their
      relationships and still function effectively, without risking later regret and
      disappointment? We address this issue by first reviewing work showing that
      because bias and accuracy are independent, they can co-exist. We next show how
      bias and accuracy are subject to different evaluative motives, relationship
      evaluations, and situations. It is argued that the pursuit of important goals is
      a time when people are motivated to feel good about their relationships. This is
      a time when relationship judgments are positively biased and relatively
      inaccurate. However, important choice points in the relationship are times when
      people are motivated to both accurately understand their relationships and to
      feel good about their relationships. These dual needs can be simultaneously met
      by becoming more accurate in epistemic-related relationship judgments while being
      more positively biased in esteem-related relationship judgments.

PMID- 15582858
TI  - Sexual economics: sex as female resource for social exchange in heterosexual
      interactions.
AB  - A heterosexual community can be analyzed as a marketplace in which men seek to
      acquire sex from women by offering other resources in exchange. Societies will
      therefore define gender roles as if women are sellers and men buyers of sex.
      Societies will endow female sexuality, but not male sexuality, with value (as in
      virginity, fidelity, chastity). The sexual activities of different couples are
      loosely interrelated by a marketplace, instead of being fully separate or
      private, and each couple's decisions may be influenced by market conditions.
      Economic principles suggest that the price of sex will depend on supply and
      demand, competition among sellers, variations in product, collusion among
      sellers, and other factors. Research findings show gender asymmetries (reflecting
      the complementary economic roles) in prostitution, courtship, infidelity and
      divorce, female competition, the sexual revolution and changing norms, unequal
      status between partners, cultural suppression of female sexuality, abusive
      relationships, rape, and sexual attitudes.

PMID- 15582859
TI  - Processing fluency and aesthetic pleasure: is beauty in the perceiver's
      processing experience?
AB  - We propose that aesthetic pleasure is a function of the perceiver's processing
      dynamics: The more fluently perceivers can process an object, the more positive
      their aesthetic response. We review variables known to influence aesthetic
      judgments, such as figural goodness, figure-ground contrast, stimulus repetition,
      symmetry, and prototypicality, and trace their effects to changes in processing
      fluency. Other variables that influence processing fluency, like visual or
      semantic priming, similarly increase judgments of aesthetic pleasure. Our
      proposal provides an integrative framework for the study of aesthetic pleasure
      and sheds light on the interplay between early preferences versus cultural
      influences on taste, preferences for both prototypical and abstracted forms, and
      the relation between beauty and truth. In contrast to theories that trace
      aesthetic pleasure to objective stimulus features per se, we propose that beauty
      is grounded in the processing experiences of the perceiver, which are in part a
      function of stimulus properties.

PMID- 15582860
TI  - Perspectives on racial phenotypicality bias.
AB  - This article reviews research examining racial phenotypicality bias--within
      category stereotypes, prejudice, and discrimination based on race-related
      phenotypic characteristics of the face. A literature review of research examining
      skin tone bias, drawing largely from work examining perceptions of Blacks in the
      United States, reveals that individuals with features typical of members of their
      racial category are perceived and treated more negatively by social perceivers.
      Furthermore, this treatment has broad implications for social status and health.
      Despite this evidence, the tendency to attend to and use within-race variation in
      phenotypic appearance has been overlooked in social psychological models of
      impression formation. However, several theoretical frameworks have recently been
      proposed to explain the role of phenotype-based expectancies in social
      representation and judgment. Drawing on the strengths of each perspective, a
      rudimentary model of racial phenotypicality bias is proposed. This analysis
      suggests that future examinations guided by the current framework (or similar
      others) can complement existing evidence toward a greater understanding of the
      role of phenotypic variation in social perception.

PMID- 15582861
TI  - On traits, situations, and their integration: a developmental perspective.
AB  - The question of whether the person or the situation is largely responsible for
      behavior has plagued psychology intermittently for the last half century. Studies
      of the heritability, stability, and consensual validity of traits have clearly
      demonstrated the existence of traits. However, there is continuing controversy
      about the role of traits and situations in the enterprise of personality
      psychology. The goal of this article is to describe how insights yielded from
      adopting a developmental approach can foster the successful integration of the
      person and the situation across the life span. Five key lessons are described:
      (a) age matters--studying different age groups can lead to biases for and against
      traits and situations; (b), if age matters, time matters more--longitudinal and
      within-participant designs demonstrate that traits and situations are
      reciprocally related; (c) examine multiple types of change--focusing on one type,
      such as mean-level change, can lead to inappropriate conclusions about the merits
      of persons or situations; (d) be sensitive to levels of analysis--the relative
      breadth of persons and situations may determine the relative influence of the
      two; (e) pay attention to process--process models lead inextricably to
      transactional explanations.

PMID- 15582865
TI  - Low attendance by basic science educators at medical education meetings.
AB  - BACKGROUND: Recently, concern has been expressed about the perception that few
      basic science educators (BSE) attend national and regional medical education
      meetings. PURPOSE: This study was designed to analyze the issues affecting BSE
      decisions about whether to attend medical education meetings. METHOD: An online
      survey was created and submitted to basic science course directors at the 128
      U.S. allopathic medical schools. RESULTS: Responses from 486 BSE suggest that
      because of the pressure to obtain research funding and achieve academic
      promotion, participation in medical education meetings is not a high priority
      with most BSE. CONCLUSIONS: BSE attendance at medical education meetings can be
      improved, but it will require joint efforts by the BSE home institution and
      medical education organizations.

PMID- 15582866
TI  - Student observations and ratings of preceptor's interactions with patients: the
      hidden curriculum.
AB  - BACKGROUND: Professional values and behavior are conveyed to students through
      both formal and informal curricular activities. PURPOSE: This study examined 1st
      year students' observations of community-based physicians' behaviors during a
      community-based clinical experience. METHODS: First-year students completed a 14
      item instrument regarding their community-based physicians' behavior with
      patients. Responses were on a 5-point scale (1 = never, 5 = all of the time).
      Descriptive statistics were computed. RESULTS: 119 students completed the
      instrument (87% response rate). Students rated aspects of physicians' demeanor
      with patients highest (mean ranges 4.7-4.57). The lowest rated item was the
      physician's view of his or her professional role (M = 3.39), eliciting patients'
      ideas about illness and treatment (M = 3.55), and modeling interviewing
      techniques learned in class (M = 3.71). CONCLUSIONS: Community-based physicians
      reinforce many professional values associated with positive role-modeling aspects
      of the physician-patient interaction.

PMID- 15582867
TI  - The role of attribution to clerk factors and contextual factors in supervisors'
      perceptions of clerks' behaviors.
AB  - BACKGROUND: Novice clinical clerks are expected to integrate smoothly into a
      medical team, often with little guidance. PURPOSE: To explore medical residents'
      and attendings' perceptions of clerk behaviors that may aid or hinder this
      integration. METHODS: Three resident focus groups and 5 attending staff
      interviews were conducted. Transcripts were analyzed using grounded theory.
      RESULTS: One hundred thirty-seven instances of clerk behaviors were identified.
      Many similar behaviors were alternately perceived as positive or negative,
      depending critically on 2 dimensions the clerk (speculated motives or personality
      traits) or the context (timing of behavior or clerk's stage of training). Motives
      and traits were mentioned nearly 3 times as often as contextual factors, possibly
      reflecting the fundamental attribution error, as described in social psychology.
      Supervisors' perceptions of why or when a behavior was enacted were an important
      factor in their perceptions. CONCLUSIONS: With explicit discussion of this
      phenomenon, supervisors' judgments might suffer from fewer biases, and students'
      integration into the team and profession might occur with less ambiguity and
      stress.

PMID- 15582868
TI  - Comparison of scholarly productivity of general and subspecialty clinician
      educators in internal medicine.
AB  - BACKGROUND: Peer-reviewed publications and extramural reputation are criteria
      used to evaluate clinician-educators for promotion. There is concern that these
      criteria may be disadvantageous to clinician-educators in generalist fields
      relative to their specialist counterparts. PURPOSE: To determine whether medicine
      subspecialists had more peer-reviewed publications and academic activities
      outside their home institution than general internal medicine (GIM) faculty, and
      to explore possible explanations for observed differences. METHOD: Cross
      sectional survey of all clinician-educators in a department of medicine at a
      leading public U.S. medical school. The survey assessed clinical duties,
      publications, and professional activities. RESULTS: Seventy-one percent (42/59)
      of clinician-educator faculty responded. GIM clinician-educators spent fewer
      months on inpatient services (p = 0.01), but more time in clinic (p = 0.05).
      Specialist clinician-educators had more peer-reviewed publications (p = 0.003),
      but total publications since entering a clinician-educator track was similar (p >
      0.2). After multiple linear regression, only academic rank (p = 0.001) and
      subspecialty membership (p = 0.005) remained significant predictors of peer
      reviewed publication. GIM faculty reported spending more scholarly time on
      "activities unlikely to result in publication" (p < 0.01). A greater proportion
      of specialists served on extramural committees (72% vs. 41%, p = 0.05) and
      lectured outside their home institution in the preceding year (92% vs. 59%, p =
      0.02). CONCLUSIONS: In this single-institution survey, specialist clinician
      educators reported more peer-reviewed publications and greater participation in
      other reputation-enhancing activities than did GIM clinician-educators.

PMID- 15582869
TI  - Is a faculty developed pretest equivalent to pre-third year GPA or USMLE step 1
      as a predictor of third-year internal medicine clerkship outcomes?
AB  - BACKGROUND: Preclinical grade point average (GPA), and United States Medical
      Licensing Examination (USMLE) Step 1 are well-known preclerkship methods of
      identifying students at risk of poor performance. These measures are not
      available at all medical schools and may be considered prejudicial. PURPOSE: Does
      an examination on the first day of a clerkship (pretest) correlate with grade
      point average (GPA) or USMLE Step 1 scores, and does it provide equivalent
      insight in predicting clerkship outcomes? METHODS: At this medical school,
      students take a faculty-developed pretest on the first day of the internal
      medicine clerkship. At the end of the clerkship, teachers recommend "clinical
      points," and students take the National Board of Medical Examiners (NBME) subject
      test. Between 1997 and 2001, data from 585 students (88%) were available.
      RESULTS: Correlations between the faculty-developed pretest, GPA, and USMLE Step
      1 scores were good, r = 0.57 to 0.66; disattenuated, r = 0.70 to 0.85. All
      variables were similar significant predictors of NBME subject test and clinical
      point outcomes. CONCLUSIONS: A faculty-developed pretest given on the 1st day of
      the internal medicine clerkship can identify students at risk of poor performance
      and may offer advantages over USMLE Step 1 and preclinical GPA.

PMID- 15582870
TI  - Effect of year in school on medical students' perceptions evaluated with the
      Cognitive Behavior Survey, Attitudes Toward Social Issues in Medicine Survey, and
      Learning Environment Questionnaire.
AB  - BACKGROUND: We administered selected scales from the Cognitive Behavior Survey,
      Attitudes Toward Social Issues in Medicine survey, and Learning Environment
      Questionnaire. We gathered data from other medical schools to put our results
      into context. PURPOSE: To present results on these scales from our own and other
      medical schools to identify the effects of "year in school" on the results.
      METHODS: We searched for articles that had cited the articles that originally
      presented the scales we used. We organized the results by type of curriculum and
      presented data from multiple points in each course. RESULTS: With a few
      exceptions, the data suggest that students' perceptions of their cognitive
      behaviors, their attitudes to social issues in medicine, and their impressions of
      the medical school learning environment deteriorate as they proceed through the
      course. In the case of PBL and hybrid curricula, this may represent a reversal of
      gains conferred by these curricula during the early phases of the course.
      CONCLUSIONS: These data provide a starting point for further study of some of the
      influences on students' perceptions of medical curricula as they proceed through
      the course.

PMID- 15582871
TI  - Effects of a disability awareness and skills training workshop on senior medical
      students as assessed with self ratings and performance on a standardized patient
      case.
AB  - BACKGROUND: People with disabilities compose one of the largest and fastest
      growing subgroups of the U.S. population. Disability and rehabilitation issues
      are not well covered in most North American medical school curricula. This
      article describes the development and assessment of a 3-hr workshop for medical
      students on disability skills and awareness. DESCRIPTION: Fourth-year medical
      students on a required clerkship participated in the workshop on alternate
      months. The efficacy of the intervention was measured by a comparison between the
      participant and control students using a pretest and posttest self-efficacy
      questionnaire and a one-station Standardized Patient (SP) Clinical Case depicting
      a hemiplegic patient and a caregiver. EVALUATION: Factor analysis of the survey
      yielded 4 subscales: Attitude, Advocacy, Interaction, Obtaining Services. There
      was a significant difference between the treatment and control group on the
      advocacy scale and on the SP communication and interstation exercises.
      CONCLUSION: A targeted educational intervention can have a positive effect on
      medical students' knowledge, skills, and attitudes toward patients with
      disabilities.

PMID- 15582872
TI  - Effect of race on ratings of hypothetical candidates for a research
      scholarship/research assistant position.
AB  - BACKGROUND: Study of the racial-ethnic biases of medical students is necessary to
      further understand health disparities. The objectives of this study were to (a)
      determine if medical students exhibit racial biases, (b) assess whether there are
      differences in racial biases among medical students who have and have not
      received a curriculum in cultural sensitivity, and (c) determine if these
      findings vary by student race-ethnicity. DESCRIPTION: We evaluated medical
      students' preferences in hiring hypothetical candidates for a research
      scholarship and a research assistant position. Each student received a packet
      containing four curricula vitae (CVs) with attached photographs. Three CVs and
      photographs were identical. The fourth CV was identical, but in half the packets
      the photograph was of an African American man and in the other half of a White
      man. Students were asked to provide ratings of suitability. EVALUATION: The
      African American candidate received better ratings than the White candidate.
      There were no differences in the ratings by student curriculum receipt or race
      ethnicity. CONCLUSION: We found no evidence that an African American candidate
      was discriminated against by medical students.

PMID- 15582873
TI  - Incorporating the fourth year of medical school into an internal medicine
      residency: effect of an accelerated program on performance outcomes and career
      choice.
AB  - BACKGROUND: To counter declining student interest in general internal medicine,
      New York Medical College and Saint Vincent's Catholic Medical Centers of New York
      implemented an experimental accelerated internal medicine curriculum that was
      provisionally approved by the American Board of Internal Medicine. DESCRIPTION:
      This accelerated program allowed selected 4th-year medical students to obtain
      credit for their 1st year of an internal medicine residency while completing
      requirements for the MD degree. EVALUATION: Career and performance outcomes for
      trainees in the accelerated and traditional internal medicine residency programs
      were compared for 6 classes of graduates. There were no statistically significant
      differences between the 2 groups in mean scores on the Intern Clinical Evaluation
      Exercise, standardized in-service exam, monthly attending evaluations, or in
      Board pass rates. However, graduates of the accelerated program were more likely
      to be in general internal medicine practice on completion of residency.
      CONCLUSIONS: The accelerated program successfully increased the number of
      trainees entering generalist practice a year earlier, and maintained academic
      standards.

PMID- 15582874
TI  - A session of multiple choice questions in the orientation process to the
      adolescent medicine rotation.
AB  - BACKGROUND: Although adolescent health care training curricula for resident
      physicians have been developed during the past 2 decades, little is known about
      the orientation process to the adolescent medicine rotation. DESCRIPTION: Since
      1996, we have incorporated a session consisting of 40 multiple-choice questions
      (MCQ) in the orientation process to our hospital-based adolescent medicine
      rotation. In this study, we evaluated residents' opinions about the MCQ format.
      EVALUATION: An anonymous questionnaire was distributed in 2002 to 123 resident
      physicians who had gone through an adolescent medicine rotation between 1996 and
      2002. A total of 68 physicians responded (55% response rate). Almost all
      respondents (99%) stated that the MCQ session was a good format to use during
      orientation to adolescent medicine. Most (85%) said that it previewed issues that
      they had to face during the rotation, 74% said that it allowed them to think
      about issues in adolescent medicine, and 65% said that it directed them to
      subjects they needed to read about for this rotation. About 45% of respondents
      stated that the MCQ session increased their level of comfort with seeing
      adolescent patients on the first few days of the rotation. The majority of
      respondents (71%) stated that an attending needed to personally review the
      answers with the residents. Of these, all said that the attending could expand
      and explore the issues, and 71% said that the attending could show locations and
      use of certain instruments (orchidometer, scoliometer, etc.) related to
      questions. Almost a fifth (18%) preferred to receive a printed answer sheet that
      they could review privately. Of these, 58% feared that review with an attending
      might prejudice the attending against them if they had errors, and 25% stated
      that it would be too stressful for them to have the attending check their answers
      on the 1st day of the rotation. Most respondents (87%) recommended that the MCQ
      format be used as part of the orientation process to other rotations as well.
      CONCLUSIONS: Resident physicians viewed the MCQ session as a good format to use
      in the orientation process to the adolescent medicine rotation. A review of the
      answers with an attending was preferred over receiving a printed answer sheet.

PMID- 15582875
TI  - A faculty development program evaluation: from needs assessment to long-term
      effects, of the teaching skills improvement program.
AB  - BACKGROUND: We evaluated whether the faculty development program, the Teaching
      Skills Improvement Program, met medical educators' needs at Hacettepe University
      Faculty of Medicine, Turkey. In a 1997 needs assessment survey, large proportions
      of 178 medical educators assessed their knowledge of educational issues and
      teaching skills as good or excellent. Nonetheless, 86% of the respondents stated
      they would like to participate in a future training program focused on the
      content indicated in the survey. DESCRIPTION AND EVALUATION: In 1998, 83 faculty
      members took part in the program and expressed a high degree of satisfaction with
      its content and organization, as well as the course trainers' teaching. Most of
      the participants got high scores on a test of knowledge related to the course
      content and performed proficiently in a microteaching session. CONCLUSION: Six
      months to a year later, large proportions of the participants reported using many
      of the training techniques in their teaching program.

PMID- 15582876
TI  - Cross-cultural faculty development: initial report of an American/Russian
      experience.
AB  - BACKGROUND: Faculty development programs can improve the teaching skills of
      medical teachers. We pilot-tested the transportability of an American-based
      faculty development seminar program to a Russian academic medical center.
      DESCRIPTION: Four seminars, based on the 7 categories of the Stanford Faculty
      Development Program model, were presented to 14 teachers at Kazan State Medical
      University. The seminars included minilectures and reviews of actual videotaped
      teaching scenario reenactments. Evaluation was performed through participants'
      self-reported ratings of teaching ability based on a validated pretest-posttest
      questionnaire. Measurements at both 1 month and 12 months postintervention were
      completed. EVALUATION: All 14 participants completed the evaluation. At both
      measured times, statistically significant improvements in the ratings of global
      teaching performance and specific teaching behaviors were reported. CONCLUSIONS:
      Our faculty development intervention was successfully transported across medical
      systems and demonstrated a positive, lasting affect on the teaching skills of a
      small number of Russian medical teachers.

PMID- 15582877
TI  - Evaluating competence using a portfolio: a literature review and web-based
      application to the ACGME competencies.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education is shifting
      its focus from a structure and process system of graduate medical education to
      one that is outcomes based, requiring all residents in training to achieve
      competence in six broad domains and presenting educators with the challenge of
      evaluation. SUMMARY: We searched the literature and reviewed all articles
      relating to portfolio assessment in medicine. In addition, we reviewed articles
      that addressed standard tools currently in use for resident performance
      assessment. The use of a portfolio allows one to incorporate a variety of
      assessment tools needed to evaluate the diverse domains of competence and also
      fosters reflective learning, which is key to professional development. From
      lessons learned through this review, we developed a Web-based evaluation
      portfolio for residency training that we describe here in the hope of
      facilitating this process for others. CONCLUSIONS: Web-based portfolio assessment
      provides an ideal venue for the evaluation of competence and has the ability to
      provide educators with a research infrastructure to practice evidence-based
      education.

PMID- 15582883
TI  - [Management of recurrences of solid tumors: Where does it stand in 2004?].

PMID- 15582884
TI  - [Local recurrence after breast conserving treatment: place of surgery].
AB  - Since the end of the sixties, conservative radiosurgical treatment is the
      standard for unifocal breast cancers < 3 cm. Retrospective and randomised trials
      confirmed identical survival, but an increased second failure's rate. Impact of
      this local failure on survival is controversy. Different prognostic factors were
      identified by the authors. Local extension of the local failure and inflammatory
      signs, the delay of its apparition and its site (witch could difference true
      local failure and new tumour) the histologic type of the local failure, the phase
      S cells rate, the N status, and characteristics of the initial tumour such as the
      N status, the tumour's size. The surgical treatment of the local failure is
      classically the salvage mastectomy associated with immediate breast
      reconstruction, often by cutaneous-muscular flaps. A second conservative
      treatment could eventually be proposed only if breast size and radiotherapy
      sequels would permit a second carcinologic and cosmetic surgical treatment: wide
      local excision and re-irradiation, unifocal tumour < 1 cm preferentially
      intraductal, well differentiated without lymphovascular embole, without extensive
      intraductal, second new cancer (in other quadrant than the initial tumor after a
      long enough delay), efficient and long time survey. RMN with identification of
      the prognostic criteria would contribute to identify the local failure witch
      could benefit of an iterative conservative treatment.

PMID- 15582885
TI  - [Locoregional recurrence of ovarian cancer: the place of surgery].
AB  - Standard therapy for advanced ovarian cancer includes cytoreductive surgery
      associated with platin based chemotherapy. Secondary surgery for recurrent
      ovarian cancer remains controversial. Actually there is not randomized trial
      based on this question. Furthermore literature shows that patients with recurrent
      disease may derive a significant survival benefit from optimal debulking. The
      datas availables indicate that prolonged disease free interval and feasibility of
      complete surgical resection are the main prognosis criteria. Proper selection of
      patients with recurrent ovarian cancer is essential to improve the therapeutic
      benefit of secondary surgery. There is a large place for trials and evaluation of
      innovatives techniques as hyperthermic intraperitoneal chemotherapy or
      intraperitoneal radio-immunotherapy.

PMID- 15582886
TI  - [Locoregional recurrent rectal cancer: the place of radiotherapy].
AB  - Currently, locoregional recurrence of rectal cancer is rare due to the
      therapeutic progress of total mesorectal excision and pre-operative radiotherapy.
      Nevertheless, a curative treatment could be proposed provided that surgical
      removal is possible and complete. Here, we will discuss the position of both
      external and intra-operative radiotherapy, and concomitant chemotherapy.
      Actually, multimodal therapy provides the best results for local control and
      overall survival. Exclusive external radiotherapy is indicated for palliative
      treatment of unresectable cases of recurrence.

PMID- 15582887
TI  - [Salvage surgery for anal canal carcinomas].
AB  - The standard treatment of epidermoid carcinoma of the anal canal consists of
      radiotherapy or chemoradiotherapy. The recommended salvage treatment for local
      failures relies on abdominoperineal resection and permits a 5-year overall
      survival rate around 50%. However, the morbidity associated with this surgery is
      important with regard to delayed perineal wound healing. New techniques for
      perineal reconstruction offer interesting solutions to limit this morbidity.
      Musculocutaneous flaps permit to fill the perineal wound left after the resection
      and in some cases to reconstruct the posterior vaginal wall. Although less
      popular, the construction of a pseudocontinent perineal colostomy enables some
      patients to avoid a permanent iliac colostomy. The surgical excision of
      metastatic inguinal nodes, followed by radiotherapy, is an alternative to
      radiotherapy alone. Surgery can also be performed after failure of radiotherapy,
      at the cost of an increased morbidity.

PMID- 15582888
TI  - [Management of recurrent soft tissue sarcoma of the retroperitoneum].
AB  - Local recurrence is the determinant of tumor-related mortality in retroperitoneal
      sarcomas because death often occurs as a result of local progression mostly
      without synchronous metastasis. Complete resection of the lesion and surgical
      margins status are the only therapeutic factors significantly associated with
      local control. Further outcome improvements need multimodal therapy since
      prognosis of these recurrences is poor with lower rates of complete resection and
      higher grade of malignancy than primary. Complete resection of the recurrence
      often requires removal of adjacent organs to achieve negative margins. External
      beam radiotherapy (EBRT), eventually associated with a boost of intra-operative
      electron beam radiotherapy (IORT) could improve the outcome in these patients.
      Preoperative timing could limit its toxicity. Chemotherapy protocols may enhance
      local and systemic outcome and can reduce the volume of high grade tumors and
      therefore allow a higher rate of complete resection. Isolated pelvic perfusion
      with local high doses chemotherapy is under investigation. Surgical excision of
      lung metastases should remain the treatment of choice, if preoperative evaluation
      indicates that complete clearance of the metastases is possible. Intra-operative
      chemotherapy after cyto-reductive surgery for the treatment of sarcomatosis is
      disappointing and complete surgery remains the cornerstone of the treatment with
      best results for low grade sarcomatosis. Adequate management at the time of
      primary presentation is likely to afford the best chance for long-term survival.

PMID- 15582889
TI  - [Surgery of recurrent soft tissue sarcoma of the extremities and the trunk wall:
      a comparison to primary sarcoma].
AB  - PURPOSE: To evaluate the place of conservative surgery in locally recurrent soft
      tissue sarcoma of the extremities and the trunk wall. METHODS: Retrospective data
      base analysis. Comparison between 32 patients with recurrent sarcoma of the
      extremities and the trunk wall to 105 comparable patients with primary sarcoma
      treated from 1996 to 1999. Tumor characteristics, quality of surgery and outcome
      are analyzed. Mean follow-up are respectively 63 and 61 months. RESULTS: Rates of
      resections R0 are 56% vs 68%, amputations 13% vs 1%, local recurrences 29% vs 9%
      (p < 0.01) in recurrent and primary sarcoma, respectively. Two prognostic sub
      groups are identified within patients with recurrent sarcoma: good (n = 25) and
      bad prognosis (n = 7) with resections R0 in 64% vs 29% of patients, five year
      survival of 76% vs 29%, respectively. The differences are due to tumor biology,
      anterior treatment, especially radiotherapy, and recurrence-free interval. A
      decision tree is developed, taking into account precedent radiotherapy and
      prognosis. CONCLUSION: In recurrent sarcoma, conservative treatment remains
      possible in a selected group of patients, combined to new means of treatment.

PMID- 15582890
TI  - [Locoregional recurrence of ORL cancer: the place of surgery].
AB  - Surgery of locoregional failures is mainly represented by salvage surgery after
      radiotherapy. Due to progress of radiotherapy, especially modification of
      fractionation and association with chemotherapy, the problem of salvage surgery
      is nowadays emphasized. Despite the reduction of postoperative mortality and
      morbidity by the use of myocutaneous flaps the complications are still frequent
      and the rehabilitation long and difficult. Oncologic results are disappointing
      too, especially in salvage surgery for oropharyngeal and hypopharyngeal tumors
      with less than a half of patients being candidates for salvage surgery and 5 year
      survival rates inferior to 30% in these patients. Laryngeal tumors are more
      favorable for salvage surgery but in the majority of the cases recurrences after
      radiotherapy require a total laryngectomy. The poor postoperative, functional and
      oncologic results after salvage surgery, especially in pharyngeal tumors must be
      taken into account for the decision of primary treatment. Regarding the important
      locoregional aggressivity of squamous cell carcinomas of the upper aerodigestive
      tract, these results must be kept in mind when preservation protocols are in
      question.

PMID- 15582891
TI  - [Locoregional recurrences of HNSCC: place of re-irradiations].
AB  - Unresectable forms of HNSCC relapses occurring in a previously irradiated area
      are relatively common and may be difficult to manage from a therapeutic point of
      view. Full dose re-irradiation with concomitant chemotherapy constitutes an
      alternative to palliative chemotherapy. Indeed, the feasibility of this approach
      has been shown, and may be associated with a curative potential in a relatively
      low proportion of these relapses.

PMID- 15582892
TI  - [The surgical management of recurrent urological malignancies after primary
      ablative therapy].
AB  - This literature review highlights the surgical management of recurrent urological
      malignancies after primary ablative therapy. In particular, recurrent
      nonseminomatous germ cell tumours (NSGCT) post-chemotherapy, recurrent bladder
      cancer post-cystectomy, loco-regional recurrence of prostate cancer after
      radiotherapy, and loco-regional recurrence of renal cell carcinoma after radical
      nephrectomy. The indications, operative technique, complications and outcomes of
      each malignancy are discussed.

PMID- 15582893
TI  - [Role of radiotherapy in recurrent gliomas].
AB  - Intracranial gliomas account for less than 2% of primary solid tumors in adults,
      but are among the most frequent causes of death from cancer in children. Their
      increasing incidence and the weak impact of treatments on the prognosis justify
      all the efforts expended to improve results. Surgery, radiation therapy (RT) and
      chemotherapy are proposed as first-line therapy, according to indications and
      modalities that remain controversial. In this palliative setting, the only
      consensus is to search for an optimal efficacy/toxicity ratio. Finally, after a
      very variable duration of local control depending on the histologic type,
      recurrence is virtually inevitable, with mainly local progression. The prognosis
      is then generally dismal, with a median survival of less than 6 months. Although
      re-operation is efficient for the rapid relief of symptoms, it is often rejected.
      After or in the absence of surgery, different chemotherapy schedules are proposed
      according to the histologic type and the patient's general status and objective
      response rates are very limited, except in the case of oligodendrogliomas. Re
      irradiation has a rather bad reputation: even as first-line therapy, total doses
      never exceed 60 Gy in 30 fractions of 2 Gy over six weeks (conventional
      fractionation). The main reasons are concerns about increasing unacceptable late
      neurologic complications and the absence of a demonstrated dose-effect beyond
      this threshold. However, some arguments have led clinicians to consider lifting
      the ban on re-irradiation. Among adult patients receiving focal RT for low-grade
      gliomas, late neurologic toxicity was recently evaluated prospectively using a
      battery of neurocognitive tests. Compared with the initial status, no significant
      deleterious effects were observed with a follow-up of at least 3 years. In
      addition, studies on primates demonstrated that the spinal cord was capable of
      repairing, at least partially, RT-induced injury. There appears to be room for
      further irradiation: the results of re-irradiation in more than 300 patients have
      been documented. The techniques used, patient selection and re-irradiation
      modalities reported were varied: interstitial brachytherapy or intraoperative-RT
      within the surgical bed, conformal 3D RT, stereotactic-RT delivered in one or
      several fractions. Treatment efficacy and toxicity endpoints were very
      heterogeneous. Nevertheless, with a clearly defined prospective assessment, re
      irradiation seems possible without any unacceptable clinical neurotoxicity under
      the following conditions: a good general status (WHO 0-1); at least a one-year
      disease-free interval; an initial WHO grade 2 or 3 histology with a maximal tumor
      diameter not exceeding 3 cm. In this very selective setting, re-irradiation is
      possible at a dose of 30 to 40 Gy, if possible in stereotactic mode, with a
      hypofractionated schedule (less than 4 Gy/fraction). Median survival exceeding
      one year is expected, the main endpoint being the control of symptoms and quality
      of life.

PMID- 15582894
TI  - [46th meeting of the American Society for Therapeutic Radiology and Oncology
      (Astro) Atlanta, 3-7 Octobre 2004].

PMID- 15582895
TI  - 4-years results of weekly trastuzumab and paclitaxel in the treatment of women
      with HER2/neu overexpressing advanced breast cancer: single institution
      prospective study.
AB  - Background. - Trastuzumab is known as an active agent in HER2/neu overexpressing
      advanced breast cancer. In the prospective study we investigated efficacy, safety
      and toxicity of trastuzumab and paclitaxel in advanced breast cancer progressing
      on previous therapy. Patients and methods. - Seventeen patients with
      histologically confirmed disease were accrued. Inclusion criteria were as
      follows: Karnofsky performance status >/= 60 %, age < 75, pretreatment with at
      least two regimens; HER2/neu by immunohistochemistry 3+ or 2+, adequate organ
      function. Trastuzumab was given 4 mg/kg i.v. as a loading dose followed by 2mg/kg
      i.v. weekly. Paclitaxel was given 80 mg/m2 i.v. weekly. Both drugs were given
      until disease progression or unacceptable toxicity. We assessed the response rate
      (RR), the time to progression (TTP), the overall survival (OS) and toxicity.
      Results. RR in the intent to treat population was 59 % (10 out of 17), including
      2 complete responses. In the median follow up of 4,3 years median TTP was 9 month
      and median OS 23 month. In total 710 cycles including 528 full dose cycles of
      trastuzumab and paclitaxel were administered. One patient developed
      hypersensitivity reaction after the first trastuzumab infusion and discontinued
      from study. Trastuzumab infusion related pyretic reaction was observed in 6
      patients. Left ventricular ejection fraction decline occurred in 2 patients
      (grade 2 and grade 3). Five patients experienced grade 3 neuropathy.
      Hematological toxicity was very modest: 1 episode of grade 4 neutropenia and
      grade 3 anemia. Other grade 3/4 toxicity: 4 episodes of grade 3 infection without
      neutropenia, grade 3 elevation of liver function tests in 1 patient, 1 episode of
      grade 3 hyperglycemia, and 1 episode of grade 3 weight gain. Other grade 3 or 4
      toxicity was not detected. Conclusion. - Trastuzumab and paclitaxel have shown
      activity and good tolerability in HER-2/neu overexpressing advanced breast cancer
      patients.

PMID- 15582897
TI  - Optimization of the schedule of gemcitabine-cisplatin combination as induction
      regimen for patients with biopsy-proven stage IIIa N2 - stage IIIb non-small-cell
      lung cancer: a prospective phase-II study.
AB  - Aim of this study was to define the optimal schedule of gemcitabine
      (GCB)?cisplatin (CDDP) combination as induction chemotherapy (CHT) in patients
      with stage IIIa pN2-IIIb non - small-cell lung cancer (NSCLC). Fifty patients
      with mediastinoscopically-proven stage-IIIa pN2 -IIIb NSCLC were treated with 3
      cycles of induction CHT followed by surgery (if staged IIIa) and three-time-daily
      accelerated radiotherapy. Chemotherapy initially consisted of 3 courses of CDDP
      100 mg?m(2) d1 plus GCB 1000 mg?m(2) dd 1,8,15 repeated every 4 weeks, than was
      modified in CDDP 80 mg?m(2) d1 plus GCB 1250 mg?m(2) dd 1,8 repeated every 3
      weeks. Twenty-nine four-week scheduled treatment cycles were firstly administered
      to 10 patients (pts): treatment-related toxicity, mainly hematological, caused a
      dose-reduction or treatment omission on day 15 in 65% of cycles. After the
      protocol was amended, 119 three-week scheduled treatment cycles were administered
      to 40 pts. Treatment-related toxicity of the new schedule caused a dose-reduction
      or treatment omission in only 10% of cycles, no patients requiring chemotherapy
      discontinuation. Thirty-seven out of fifty patients (74%, 95% CI: 60-85%)
      achieved a partial response, 7 had stable disease and 6 had disease progression.
      Similar activity was seen with both schedules. One nodal pathological complete
      remission was observed among the 24 pts who underwent surgery. At present, with a
      median follow-up of 13 months (mos), 2-year (y) survival of all the 50 pts and of
      the 24 pts staged IIIa who underwent surgery is estimated as 37% (95% CI: 24-58%)
      and 47% (95%CI: 27-80%), respectively. When given as induction chemotherapy, a
      three-week schedule of CDDP plus GCB combination appeared to be effective, with
      lower toxicity and better compliance than a four-week schedule.

PMID- 15582898
TI  - Gefitinib (Iressa, ZD1839): a novel targeted approach for the treatment of solid
      tumors.
AB  - Recent advances in cancer therapy have resulted in the development of drugs that
      target mechanisms involved in neoplastic change and angiogenesis. One example is
      gefitinib ('Iressa', ZD1839), an orally-active epidermal growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI) that blocks EGFR signaling in vitro, thereby
      inhibiting the growth, proliferation and survival of many solid tumors. Clinical
      trial data show that gefitinib monotherapy is generally well tolerated in
      patients with a wide range of tumor types (including lung, head and neck, colon,
      breast, and prostate cancers). The most common adverse events (AEs) were mild and
      reversible skin and gastrointestinal disorders (National Cancer Institute common
      toxicity criteria grade 1/2). Few drug-related grade 3/4 skin and
      gastrointestinal disorders were observed, and drug-related hematologic AEs were
      uncommon. The clinical benefit of gefitinib in non-small-cell lung cancer
      (NSCLC), head and neck, colon, breast, and prostate cancer is being investigated,
      as antitumor activity has been observed in a range of solid tumors, including
      NSCLC. In two large phase II NSCLC trials (IDEAL ['Iressa' Dose Evaluation in
      Advanced Lung Cancer] 1 and 2) objective tumor responses of 18.4% and 11.8%, and
      disease control rates (complete and partial responses plus stable disease) of
      54.4% and 42.2%, respectively, were seen in patients given 250 mg/day gefitinib.
      Additionally, disease-related symptoms improved in 40.3% and 43.1% of patients,
      and improved quality of life was experienced by 23.9% and 34.3% patients in IDEAL
      1 and 2, respectively. Furthermore, the majority of patients who had an objective
      response also experienced symptom improvement. Gefitinib has been approved for
      the treatment of advanced NSCLC in Japan, the USA, and other countries. This
      review discusses the potential of gefitinib in a wide range of solid tumors.
      'Iressa' is a trademark of the AstraZeneca group of companies.

PMID- 15582899
TI  - Analysis of the tomato fruit growth response to temperature and plant fruit load
      in relation to cell division, cell expansion and DNA endoreduplication.
AB  - BACKGROUND AND AIMS: To better understand the regulation of fruit growth in
      response to environmental factors, the effects of temperature and plant fruit
      load on cell number, cell size and DNA endoreduplication were analysed. METHODS:
      Plants were grown at 20/20 degrees C, 25/25 degrees C and 25/20 degrees C
      day/night temperatures, and inflorescences were pruned to two ('2F') or five
      ('5F') flowers. KEY RESULTS AND CONCLUSIONS: Despite a lower fruit growth rate at
      20/20 degrees C, temperature did not affect final fruit size because of the
      compensation between cell number and size. The higher cell number at 20/20
      degrees C (9.0 x 10(6) against 7.9 x 10(6) at 25/25 degrees C and 7.7 x 10(6) at
      25/20 degrees C) resulted from an extended period of cell division, and the
      smaller cell size was due to a shorter period of expansion rather than a lower
      expansion rate. By contrast, the lower fruit growth rate and size of 5F fruits
      compared with 2F fruits resulted from the slow down of cell expansion, whereas
      the number of cells was hardly affected in the proximal fruit. However, within
      the inflorescence the decreasing gradient of fruit size from proximal to distal
      fruits was due to a decrease in cell number with similar cell size. Fruit size
      variations within each treatment were always positively correlated to variations
      in cell number, but not in cell size. Negative correlations between cell size and
      cell number suggested that cells of tomato pericarp can be seen as a population
      of competing sinks. Mean ploidy was slightly delayed and reduced in 5F fruits
      compared with 2F fruits. It was highest at 25/25 degrees C and lowest at 25/20
      degrees C. Treatments did not affect ploidy and cell size in similar ways, but
      within each treatment, positive correlations existed between mean ploidy and cell
      size, though significant only in the 2F-25/20 treatment.

PMID- 15582911
TI  - Conflict of interest is not just about advising pharmaceutical companies.

PMID- 15582912
TI  - Alcohol, wine and mental health: focus on dementia and stroke.
AB  - The relative risks of coronary heart disease (CHD) and overall mortality are
      reduced by moderate consumption of alcoholic beverages, particularly wine, which
      has major implications for public health. It appears likely that this beneficial
      effect of alcohol will soon be extended to some mental disorders. Although data
      on psychosis and mood and anxiety disorders are currently lacking, it appears
      that the relative risks of developing ischaemic stroke and Alzheimer's or
      vascular dementia are also lowered by moderate alcohol consumption. Such findings
      are still tentative because of the inherent methodological problems involved in
      population-based epidemiological studies, and it is unclear whether the benefit
      can be ascribed to alcohol itself or to other constituents specific to wine such
      as polyphenols. Plausible biological mechanisms have been advanced for the
      protective effect of alcohol and wine against CHD, many of which will also play
      roles in their protective actions against cerebrovascular disease and dementia.
      The specific antioxidant properties of wine polyphenols may be particularly
      important in preventing Alzheimer's disease. Because of the substantially
      unpredictable risk of progression to problem drinking and alcohol abuse, the most
      sensible advice to the general public is that heavy drinkers should drink less or
      not at all, that abstainers should not be indiscriminately encouraged to begin
      drinking for health reasons, and that light to moderate drinkers need not change
      their drinking habits for health reasons, except in exceptional circumstances.

PMID- 15582914
TI  - Moderate differences in circulating corticosterone alter receptor-mediated
      regulation of 5-hydroxytryptamine neuronal activity.
AB  - Circulating glucocorticoid levels vary with stress and psychiatric illness and
      play a potentially important role in regulating transmitter systems that regulate
      mood. To determine whether chronic variation in corticosterone levels within the
      normal diurnal range altered the control of 5-hydroxytryptamine (5-HT) neuronal
      activity, male rats were adrenalectomized and implanted with either a 2% or 70%
      corticosterone/cholesterol pellet (100 mg). Two weeks later, the regulation of 5
      HT neuronal activity in the dorsal raphe nucleus was studied by in vitro
      electrophysiology. At this time, serum corticosterone levels approximated the low
      point (2%) and mid-point (70%) of the diurnal range. The excitatory response of 5
      HT neurones to the alpha1-adrenoceptor agonist phenylephrine (1-11 microM) was
      significantly greater in the 2% group compared to the 70% group. By contrast, the
      inhibitory response to 5-HT (10-50 microM) was significantly lower in the 2%
      group compared to the 70% group. Thus, chronic variation in circulating
      corticosterone over a narrow part of the normal diurnal range causes a shift in
      the balance of positive and negative regulation of 5-HT neurones, with increased
      alpha 1-adrenoceptor-mediated excitation and reduced 5-HT-mediated autoinhibition
      at lower corticosterone levels. This shift would have a major impact on control
      of 5-HT neuronal activity.

PMID- 15582915
TI  - Effect of chronic lithium treatment on glucocorticoid and 5-HT1A receptor
      messenger RNA in hippocampal and dorsal raphe nucleus regions of the rat brain.
AB  - The therapeutic mechanism of action of lithium in the treatment of bipolar
      disorder is not well understood. Dysfunction of both 5-HT(1A) receptor mediated
      neurotransmission and the glucocorticoid receptor is associated with mood
      disorders, and preclinical studies suggest that lithium treatment can modulate
      these receptor subtypes. In this study, we investigated the effect of chronic
      lithium treatment on 5-HT(1A) receptors and glucocorticoid receptors in the rat
      brain. Male Sprague-Dawley rats were treated with lithium (3 mmol/kg/day) or
      saline for 28 days via subcutaneous implanted mini-osmotic pumps. After 28 days
      of treatment, the expression of mRNA for 5-HT(1A) receptors and glucocorticoid
      receptors in the rat hippocampus and dorsal raphe nucleus was determined by in
      situ hybridization histochemistry. Chronic administration of lithium decreased
      mRNA coding for post-synaptic 5-HT(1A) receptors in hippocampal subregions but
      not for somatodentritic 5-HT(1A) receptors in the dorsal raphe nucleus. Chronic
      administration of lithium did not affect mRNA coding for glucocorticoid receptors
      in hippocampal subregions or in the dorsal raphe nucleus. Mean plasma lithium
      levels in the lithium-treated group were 0.50 +/- 0.03 mmol/l; all animals
      appeared healthy and maintained a normal increase in body weight. Given recent
      reports implicating hypersensitive post-synaptic 5-HT(1A) receptors in bipolar
      manic patients, the present study suggests that down-regulation of this receptor
      population may be important in the therapeutic mechanism of action of lithium.

PMID- 15582916
TI  - Chronic cannabinoid exposure produces lasting memory impairment and increased
      anxiety in adolescent but not adult rats.
AB  - Although many studies have examined the acute behavioural effects of cannabinoids
      in rodents, few have examined the lasting effects of cannabinoids at different
      developmental ages. This study compared lasting effects of cannabinoid exposure
      occurring in adolescence to that occurring in early adulthood. Forty, 30-day old
      (adolescent) and 18, 56-day old (adult) female albino Wistar rats were injected
      with vehicle or incremental doses of the cannabinoid receptor agonist (-)-cis-3
      [2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol
      (CP 55,940) once per day for 21 consecutive days (150, 200 and 300 microg/kg i.p.
      for 3, 8 and 10 days, respectively). Following a 21-day drug-free period, working
      memory was assessed using an object recognition task. Locomotor activity was also
      measured in the object recognition apparatus via a ceiling-mounted passive
      infrared sensor. Three days later, anxiety was assessed using a social
      interaction test. In the object recognition task, significantly poorer working
      memory was observed in the adolescent but not adult CP 55,940-treated rats.
      Adolescent, but not adult CP 55,940-treated rats, also exhibited a significant
      decrease in social interaction with a novel conspecific. These results suggest
      that chronic exposure to a cannabinoid receptor agonist well after the immediate
      postnatal period, but before reaching sexual maturity, can lead to increased
      anxiety and a lasting impairment of working memory.

PMID- 15582913
TI  - Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric
      disorders.
AB  - Cigarette smoking rates in the American population are approximately 23%, whereas
      rates of smoking in clinical and population studies of individuals with
      neuropsychiatric disorders are typically two- to four-fold higher. Studies
      conducted in a variety of neuropsychiatric populations [e.g. attention-deficit
      hyperactivity disorder (ADHD), Alzheimer's disease, schizophrenia] have
      collectively suggested that nicotine may be efficacious in remediating selected
      cognitive deficits associated with these disorders, thus providing a framework
      for understanding the specific vulnerability of these patients to smoking
      initiation and maintenance. However, the specific gain in cognitive performance
      produced by nicotine administration in healthy subjects with normal cognitive
      function is less clear. This article reviews our current understanding of central
      nicotinic acetylcholine receptor (nAChRs) systems in normal and neuropsychiatric
      disease states and, specifically, their role with respect to cognitive
      dysfunction and clinical symptoms in several specific neuropsychiatric
      populations, including ADHD, Alzheimer's disease, Parkinson's disease, Tourette's
      Disorder, schizophrenia and affective disorders. The potential benefits of
      nicotinic agents for therapeutic use in neuropsychiatric disorders is discussed,
      as well as directions for further research in this area.

PMID- 15582917
TI  - P-glycoprotein is a factor in the uptake of dextromethorphan, but not of
      melperone, into the mouse brain: evidence for an overlap in substrate specificity
      between P-gp and CYP2D6.
AB  - In this study, the role of P-glycoprotein (P-gp) for the pharmacokinetics of
      dextromethorphan, a CYP2D6 substrate, and of melperone, a CYP2D6 inhibitor, was
      investigated. The substances were administered subcutaneously near the nape of
      the neck of wild-type mice and of abcb1ab (-/-) mice. One hour after injection,
      concentrations of the two drugs in cerebrum, plasma and in different organs were
      measured by high-performance liquid chromatography. No significant differences
      between wild-type mice and abcb1ab (-/-) mice were observed for melperone,
      suggesting that P-gp is not involved in the uptake of melperone into the brain or
      other organs of mice. The concentration of dextromethorphan in the brain was more
      than twice as high in abcb1ab (-/-) mice compared to wild-type mice. Therefore, P
      gp appears to be a factor in the uptake of dextromethorphan into the mouse brain,
      and abcb1-polymorphisms need to be considered for CYP2D6 phenotyping experiments
      with this drug. There is an overlap in substrate specificity between P-gp and
      CYP2D6. P-gp is a factor in the uptake of dextromethorphan, but not of melperone.

PMID- 15582918
TI  - Amphetamine decreases the expression and acquisition of appetitive conditioning
      but increases the acquisition of anticipatory responding over a trace interval.
AB  - The effects of amphetamine on selective learning were tested in a trace
      conditioning procedure, in which the informativeness of the conditioned stimulus
      (CS) (noise) was manipulated through the introduction of a time interval before
      the delivery of the unconditioned stimulus (UCS) (food). The results showed that
      d-amphetamine (0.5 and 1.5 mg/kg) impaired both the expression (Experiment 1b)
      and acquisition (Experiment 2) of appetitive conditioning. This was true for both
      trace and contiguously conditioned groups. The effects of the 0.5 mg/kg dose of d
      amphetamine were not attributable to general motor (measured pre-CS) or
      motivational (measured post-UCS) effects of the drug. Moreover, the same pattern
      of effects (impaired appetitive conditioning, irrespective of the trace interval
      between CS and UCS) was confirmed in drug-free extinction tests. By contrast to
      the general depression in the acquisition and expression of associative learning
      observed under amphetamine, the 0.5 mg/kg dose promoted the acquisition of
      anticipatory responses made later in the trace interval (in Experiment 2 but,
      again, not the expression of previous conditioning in Experiment 1b). This
      suggests a dissociable effect of low-dose d-amphetamine on learning about the
      temporal relationship between CS and UCS.

PMID- 15582919
TI  - A pictorial Stroop paradigm reveals an alcohol attentional bias in heavier
      compared to lighter social drinkers.
AB  - The findings obtained with the textual Stroop paradigm, testing for an
      attentional bias towards alcohol stimuli in heavier compared to lighter social
      drinkers, are limited in number and inconsistent in outcome. Using a pictorial
      rather than textual Stroop paradigm for the first time in alcohol research, a
      significant alcohol attentional bias is reported in heavier social drinkers
      compared to lighter social drinking controls. According to Cohen's scheme, the
      signifant effect size is classified as 'large'. The presence of an alcohol
      attentional bias helps to explain the perpetuation of abusive/dependent
      consumption and the frequency of post-treatment relapse. In a similar vein, these
      results add to the evidence that a differential alcohol attentional bias might
      also be present between two levels of social drinking and, in heavier social
      drinkers, has the potential to impact on the contents of awareness and the flow
      of thought towards alcohol. In this respect, it extends the small group of other
      perceptual-cognitive effects measured in social drinkers (alcohol cue reactions,
      alcohol associations and alcohol expectancies) that can influence the initiation
      of consumption in some social drinkers.

PMID- 15582920
TI  - Reinforcing, subject-rated, performance and physiological effects of
      methylphenidate and d-amphetamine in stimulant abusing humans.
AB  - Methylphenidate has potential for abuse because it produces behavioural effects
      similar to those observed with other abused stimulants, such as d-amphetamine and
      cocaine. The aim of this study was to further characterize the abuse potential of
      oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers
      were recruited to participate in this study, which consisted of seven dose
      conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg)
      and placebo. The reinforcing effects of these drugs were assessed during a self
      administration session (preceded by a sampling session for each condition) with a
      modified progressive-ratio procedure. Subject-rated, performance and
      physiological effects were assessed concurrently during both the sampling and
      self-administration sessions. The intermediate dose of methylphenidate and d
      amphetamine increased responding significantly above placebo levels. Both
      methylphenidate and d-amphetamine produced dose-dependent increases in stimulant
      like subject ratings (e.g. Active, Alert, or Energetic and High), but the effects
      of these drugs were not isomorphic. These findings are consistent with
      epidemiological data and previous findings from laboratory studies that suggest
      methylphenidate has at least some abuse potential.

PMID- 15582921
TI  - Two new neurophysiological indices of cocaine craving: evoked brain potentials
      and cue modulated startle reflex.
AB  - Craving for cocaine is one of the hallmarks of cocaine dependence. One of the
      problems with craving is its measurement. Traditional psychophysiological indices
      such as skin conductance and heart rate have yielded contradictory results. These
      measures of craving were found to correlate only moderately with self-reported
      craving. In the present study, event-related brain potentials (ERPs) and the cue
      modulated startle response (CMSR) are evaluated as indices for cocaine craving.
      Twenty-one abstinent cocaine-dependent subjects were divided into high and low
      cravers group based on the median split of self-reported craving scores. ERPs and
      CMSR were measured when subjects watched neutral, pleasant, unpleasant and
      cocaine-related pictures. Overall, it was found that cocaine-dependent subjects
      showed augmented slow-positive waves (SPWs) of the ERP on the cocaine pictures
      compared to neutral pictures. Only high cravers showed larger SPWs on the cocaine
      cues, suggesting an association between cue-elicited SPWs and self-reported
      cocaine craving. By contrast to the ERP measures, CMSR did not differentiate
      between cocaine pictures and neutral pictures. In addition, no differences
      between the low- and high cravers on the CMSR measure were found. The present
      results show that the evoked-potentials paradigm provides promising results to
      index cue-elicited craving. The use of startle modulation deserves further
      investigation.

PMID- 15582922
TI  - The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic
      disorder.
AB  - Antidepressants that inhibit the reuptake of serotonin (5-HT) are particularly
      effective in the treatment of panic disorder. Evidence suggests that increased 5
      HT availability is important for the anti-panic effect of serotonergic drugs and
      in maintaining the response to selective serotonin reuptake inhibitors (SSRIs).
      Tianeptine is an antidepressant with 5-HT reuptake enhancing properties (i.e. the
      opposite pharmacological profile to that of SSRIs). Therefore, no effect would be
      expected in panic disorder. The aim of the present study was to compare the
      effect of tianeptine with that of paroxetine, a selective 5-HT reuptake inhibitor
      with demonstrated efficacy in panic disorder, on the vulnerability to a
      laboratory panic challenge in panic disorder patients. Twenty panic disorder
      patients were treated with either tianeptine or paroxetine for a period of 6
      weeks, in a randomized, double-blind, separate group design. The reaction to a
      35% CO(2) panic challenge was assessed at baseline and after treatment.
      Improvement on several clinical scales was also monitored. Tianeptine, as well as
      paroxetine, showed a significant reduction in vulnerability to the 35% CO(2)
      panic challenge. In spite of their opposite influence on 5-HT uptake, both
      tianeptine and paroxetine appeared to reduce the reaction to the panic challenge.
      These results raise questions about the necessity of 5-HT uptake for the
      therapeutic efficacy of anti-panic drugs.

PMID- 15582923
TI  - Combination therapy with venlafaxine and carbamazepine in depressive patients not
      responding to venlafaxine: pharmacokinetic and clinical aspects.
AB  - The chiral antidepressant venlafaxine (VEN) is both a serotonin and a
      norepinephrine uptake inhibitor. CYP2D6 and CYP3A4 contribute to its metabolism,
      which has been shown to be stereoselective. Ten CYP2D6 genotyped and depressive
      (F32x and F33x, ICD-10) patients participated in an open study on the
      pharmacokinetic and pharmacodynamic consequences of a carbamazepine augmentation
      in VEN non-responders. After an initial 4-week treatment with VEN (195 +/- 52
      mg/day), the only poor metabolizer out of 10 depressive patients had the highest
      plasma concentrations of S-VEN and R-VEN, respectively, whereas those of R-O
      demethyl-VEN were lowest. Five non-responders completed the second 4-week study
      period, during which they were submitted to a combined VEN-carbamazepine
      treatment. In the only non-responder to this combined treatment, there was a
      dramatic decrease of both enantiomers of VEN, O-demethylvenlafaxine, N
      desmethylvenlafaxine and N, O-didesmethylvenlafaxine in plasma, which suggests
      non-compliance, although metabolic induction by carbamazepine cannot entirely be
      excluded. The administration of carbamazepine [mean +/- SD, range: 360 +/- 89
      (200-400) mg/day] over 4 weeks did not result in a significant modification of
      the plasma concentrations of the enantiomers of VEN and its O- and N-demethylated
      metabolites in the other patients. In conclusion, these preliminary observations
      suggest that the combination of VEN and carbamazepine represents an interesting
      augmentation strategy by its efficacy, tolerance and absence of pharmacokinetic
      modifications. However, these findings should be verified in a more comprehensive
      study.

PMID- 15582924
TI  - The MTHFR C677T polymorphism is associated with depressive episodes in patients
      from Northern Ireland.
AB  - Low plasma folate and its derivatives have been linked with depressive disorders
      in studies dating back over 30 years. A thermolabile variant (677C>T) of the
      enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low
      serum folate. The present study aimed to explore whether the thermolabile variant
      of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T
      genotype frequencies in a cohort of patients (mean age 48 years) with depressive
      disorder (n = 100) were compared with those in age- and sex-matched controls.
      Serum levels of folate, homocysteine and vitamin B(12) were also compared between
      groups. The thermolabile variant of MTHFR was significantly more common in the
      group with a history of depressive disorder (P= 0.03). Serum levels of folate,
      homocysteine and vitamin B(12) did not differ significantly between groups. A
      MTHFR C677T genotype is associated with increased risk of depressive episodes in
      this homogenous patient population.

PMID- 15582925
TI  - Ecstasy/MDMA and cannabis: the complexities of their interactive
      neuropsychobiological effects.

PMID- 15582926
TI  - State transitions: an example of acclimation to low-light stress.
AB  - State 1-State 2 transitions ('state transitions') are a rapid physiological
      adaptation mechanism that adjusts the way absorbed light energy is distributed
      between photosystem I and photosystem II. They occur in both green plants and
      cyanobacteria, although the light-harvesting complexes involved are very
      different. Which aspects of the mechanism are conserved in green plants and
      cyanobacteria and which may be different, are discussed. It is shown that
      phycobilisome mobility is necessary for state transitions in cyanobacteria. A
      conserved cyanobacterial gene (rpaC) that plays a very specific role in state
      transitions has been identified. There is still debate about the physiological
      role of state transitions. Comparison of the growth properties of the rpaC
      deletion mutant with the wild-type gives us a way of directly addressing the
      question. It was found that state transitions are physiologically important only
      at very low light intensities: they play no role in protection from
      photoinhibition. Thus state transitions are a way to maximize the efficiency of
      light-harvesting at low light intensities.

PMID- 15582927
TI  - Changes in intracellular and apoplastic peroxidase activity, ascorbate redox
      status, and root elongation induced by enhanced ascorbate content in Allium cepa
      L.
AB  - Onions (Allium cepa L.) treated with external ascorbic acid or with the immediate
      precursor of its synthesis L-galactono-gamma-lactone show a stimulated elongation
      rate of the roots and an increase in the number of new radicles appearing at the
      bulb base. Treatment with both molecules resulted in an enhanced accumulation of
      ascorbate and dehydroascorbate along the root axis, but the distribution of these
      redox forms was not uniform along the root, as detected in intracellular
      (symplastic) and extracellular (apoplastic) compartments. Thus, those radicular
      zones metabolically more active, such as the meristem and the elongation zone,
      accumulated the highest amount of both redox forms of ascorbate. On the other
      hand, ascorbate and L-galactono-gamma-lactone also stimulated cytosolic glucose-6
      phosphate dehydrogenase activity and inhibited peroxidase activity as deduced
      from in vivo and in vitro experiments. Differences were also found when comparing
      apoplastic and symplastic activities. These results are compatible with the idea
      of an ascorbate-mediated stimulation of root growth by inhibiting cell wall
      stiffening and increasing root metabolism.

PMID- 15582928
TI  - The dependence of leaf hydraulic conductance on irradiance during HPFM
      measurements: any role for stomatal response?
AB  - This paper examines the dependence of whole leaf hydraulic conductance to liquid
      water (K(L)) on irradiance when measured with a high pressure flowmeter (HPFM).
      During HPFM measurements, water is perfused into leaves faster than it evaporates
      hence water infiltrates leaf air spaces and must pass through stomates in the
      liquid state. Since stomates open and close under high versus low irradiance,
      respectively, the possibility exists that K(L) might change with irradiance if
      stomates close tightly enough to restrict water movement. However, the dependence
      of K(L) on irradiance could be due to a direct effect of irradiance on the
      hydraulic properties of other tissues in the leaf. In the present study, K(L)
      increased with irradiance for 6 of the 11 species tested. Whole leaf conductance
      to water vapour, g(L), was used as a proxy for stomatal aperture and the time
      course of changes in K(L) and g(L) was studied during the transition from low to
      high irradiance and from high to low irradiance. Experiments showed that in some
      species K(L) changes were not paralleled by g(L) changes. Measurements were also
      done after perfusion of leaves with ABA which inhibited the g(L) response to
      irradiance. These leaves showed the same K(L) response to irradiance as control
      leaves. These experimental results and theoretical calculations suggest that the
      irradiance dependence of K(L) is more consistent with an effect on extravascular
      (and/or vascular) tissues rather than stomatal aperture. Irradiance-mediated
      stimulation of aquaporins or hydrogel effects in leaf tracheids may be involved.

PMID- 15582929
TI  - A red beet (Beta vulgaris) UDP-glucosyltransferase gene induced by wounding,
      bacterial infiltration and oxidative stress.
AB  - Mechanical wounding, infiltration with P. syringae or A. tumefaciens, and
      exposure to an H(2)O(2)-generating system (Glc/Glc oxidase) induce betacyanin
      synthesis in red beet (Beta vulgaris) leaves. These conditions also induced the
      expression of BvGT, a gene encoding a glucosyltransferase (GT) from Beta
      vulgaris. BvGT has a high similarity to Dorotheanthus bellidiformis betanidin-5
      GT involved in betacyanin synthesis. Furthermore, the transient expression of a
      BvGT antisense construct resulted in the reduction of BvGT transcript
      accumulation and betanin synthesis, suggesting a role for this gene product in
      betacyanin glucosylation. In addition, the NADPH oxidase inhibitor, diphenylene
      iodonium (DPI), inhibited the accumulation of the BvGT transcript in response to
      infiltration with Agrobacterium tumefaciens. Hence, this result suggests that ROS
      produced by a plasma membrane NADPH oxidase may act as a signal to induce BvGT
      expression, necessary for betanin synthesis after wounding and bacterial
      infiltration.

PMID- 15582930
TI  - Tight regulation of expression of two Arabidopsis cytosolic Hsp90 genes during
      embryo development.
AB  - The spatial and temporal distribution of expression of two cytosolic members of
      the AtHsp90 gene family was assessed during early development. In stressed
      transgenic plants bearing the AtHsp90-3 promoter, beta-glucuronidase (GUS)
      activity was strong in meristematic tissues. Expression was also detected in
      vascular tissues, leaf veins, siliques, and in pollen sacs. The promoter induced
      gene expression after heat shock in a time-course dependent manner. AtHsp90-1
      promoter activity was low throughout the early stages of embryo development but
      high just before embryo maturation, with expression most prominent in cotyledons.
      AtHsp90-3 promoter activity was almost constant and restricted to the root and
      the cotyledon tips of the embryo. This highly specific spatial distribution of
      GUS activity changed when the tissues were heat-stressed. Both promoters were
      also active in unstressed mature pollen grains and during pollen germination. The
      results shown here indicate that different regulatory and developmental
      mechanisms control and differentiate the expression of the two cytosolic members
      of the Arabidopsis AtHsp90 gene family under normal conditions. The developmental
      and restricted pattern of expression of the AtHsp90-1 and -3 gene promoters in
      unstressed transgenic plants suggest prominent and distinctive roles of these two
      genes during different developmental processes.

PMID- 15582931
TI  - Suzuki segregation in a binary Cu-Si alloy.
AB  - Suzuki segregation to stacking faults and coherent twin boundaries has been
      investigated in a Cu-7.15 at.% Si alloy, heat-treated at temperatures of 275, 400
      and 550 degrees C, using field-emission gun transmission electron microscopy.
      Silicon enrichment was observed at the stacking fault plane and decreased
      monotonically with increasing annealing temperature. This increase in the
      concentration of solute at the fault is due to the stacking fault energy being
      lowered at higher values of the electron-to-atom ratio of the alloy. From a
      McLean isotherm, the binding energy for segregation was calculated to be -0.021
      +/- 0.019 eV atom(-1). Hardly any segregation was observed to coherent twin
      boundaries in the same alloy. This is because a twin has a lower interfacial
      energy than a stacking fault, so that the driving force for segregation is
      diminished.

PMID- 15582932
TI  - Behaviors of surfactant atoms on Si(001) surface.
AB  - The behaviors of surfactant atoms for thin film growth on the Si(001) surface
      formed by molecular beam epitaxy were observed. At first, heterointerfaces on
      Si/Ge and Ge/Si without surfactant effect were investigated and are discussed on
      the basis of thermodynamics of surfaces and surface diffusion. The mechanism of
      island formation as a later stage of Stranski-Krastanov growth mode is also
      discussed. Surfactant effects of Bi atoms on the heteroepitaxial structures were
      investigated experimentally. Behavior of Sb as a surfactant was also observed and
      compared with the results of Bi. Mechanisms for improvements in the abruptness at
      heterointerfaces of Si/Ge/Si as well as suppression of island formation are
      discussed. The formation of atomic-scale wires of Bi was observed. The structure
      of Bi wires at high temperatures is described.

PMID- 15582933
TI  - Application of valence electron energy-loss spectroscopy and plasmon energy
      mapping for determining material properties at the nanoscale.
AB  - Measuring material properties at the nanoscale is critical to understanding the
      behavior of nanostructured materials. In this paper, we demonstrate a novel
      technique that allows direct determination and imaging of physical properties of
      individual nanoprecipitates and nanoparticles using energyfiltering transmission
      electron microscopy combined with valence electron energy-loss spectroscopy
      (VEELS). We show that strong scaling correlations exist between the plasmon
      energy and elastic properties, hardness, valence electron density and cohesive
      energy. We apply these scaling relationships to characterize the elastic
      properties of metastable nanoprecipitates in a Ti-based structural alloy and the
      hardness of diesel-engine soot particles. We also discuss additional factors that
      need to be considered when using plasmons as a quantitative tool for nanoscale
      property measurement. The results show that VEELS has the potential to determine
      multiple solid-state properties of materials at the nanoscale, establishing a new
      capability for analytical electron microscopy.

PMID- 15582934
TI  - HVEM characterization of crack tip dislocations in silicon crystals.
AB  - Crack tip dislocations in silicon crystals have been studied using high voltage
      electron microscopy (HVEM). The dislocation images have been investigated by
      comparing the observed images to those that were simulated. Dislocation images
      were computed in the conditions g x b = 0, 1 or 2 (g: diffraction vector, b:
      Burgers vector). The characteristics of 60 degrees dislocations were examined in
      detail since these dislocations are not characterized only by the condition g x b
      = 0 criterion. The computed images were in good agreement with those observed by
      HVEM. Residual contrasts of 60 degrees dislocations under the condition g x b = 0
      exhibited characteristic black-and-white contrasts, which can contribute to the
      characterization of the dislocations. Such characterization of dislocations is
      essential in order to clarify the dislocation mechanism which controls the
      fracture toughness of materials.

PMID- 15582935
TI  - Bandgap mapping for III-V quantum well by electron spectroscopy imaging.
AB  - The concept of 'bandgap mapping' was proposed originally to map the inhomogeneity
      of band energy in III-V semiconductors with a spatial resolution of a few
      nanometres in a scanning transmission electron microscope with the focus beam
      mode. In this paper, several techniques were developed to demonstrate the
      possibility to map the distribution of bandgap energies for GaN/AlN quantum-well
      structures using electron spectroscopy imaging (ESI). The phase correlation
      function was used to register different energy-loss images among ESI series with
      an accuracy of 1 pixel. The energy dispersion of ESI series was improved by a
      fast Fourier transform interpolation method. An iterative multivariable least
      square algorithm was derived to refine the fitting of the single scattering
      distribution to an analytic form of the density of states function a(E -
      E(g))(0.5). The inhomogeneity of the band energy of the quantum well can be
      revealed from the band-energy map. A threshold filter method is applied to
      estimate the average value and SD of the bandgap energy from barrier and well
      regions in the energy map. The average bandgap energy of AlN and GaN is
      determined to be 5.62 +/- 0.35 and 3.87 +/- 0.36 eV, respectively. The effect of
      delocalization on the accuracy of band-energy determination is discussed. The
      2sigma(E(g)) accuracy of this analysis is comparable to half of the energy
      resolution of the ESI experiment.

PMID- 15582936
TI  - Voltage refinement by deficit HOLZ line geometry.
AB  - A method of refining electron beam voltage from deficit line intersections, using
      a quasi-kinematic scattering approximation, is described and applied to a silicon
      standard. It is shown that dynamical corrections are necessary for higher-index
      zone axes, such as 310 and 411, where a single deficit line associated with one
      dominant Bloch state is visible. This leads to a substantial difference in the
      refined voltage compared with that obtained from a purely kinematic
      approximation. Neglect of this dynamical correction term effectively invokes a
      systematic error that may lead to high precision but poor accuracy in higher
      order Laue zone measurements of beam voltage or lattice parameters. Although
      relatively small, differences in the dynamical correction necessary for these two
      zones are confirmed experimentally for 100-300 keV electrons.

PMID- 15582937
TI  - In situ ESEM observation of melting silver and Inconel on an Al(2)O(3) powder
      bed.
AB  - A hot stage in an environmental scanning electron microscope (ESEM) was used for
      in situ infiltration experiments. Pressureless infiltration of a porous Ti
      activated Al(2)O(3) preform has been investigated at temperatures up to 1530
      degrees C under two atmospheres (He and H(2)O((g))). A brief description of the
      operating and the experimental set-up is given. Silver and Inconel (Ni
      superalloy) infiltration experiments demonstrate the in situ potential of the
      ESEM at temperatures up to 1500 degrees C.

PMID- 15582938
TI  - High-resolution transmission electron microscopy study of Ca(3)Co(4)O(9).
AB  - The crystal structure of Ca(3)Co(4)O(9) was investigated using high-resolution
      transmission electron microscopy (HRTEM) and the image-simulation method. The
      c(*) was 10.8A and the b parameters were 4.56A for the Ca(2)CoO(3) block and
      2.82A for the CoO(2) sheet. The [110] zone axis HRTEM images confirmed that
      Ca(3)Co(4)O(9) has a modulated layered structure with modulation. For the first
      time, the atomic positions of the Ca and Co atoms in the Ca(2)CoO(3) block were
      identified, corresponding to three rows of dark spots in the [110] direction. The
      observed HRTEM images for Ca(2)CoO(3) agreed well with the calculated images
      based on the structural model obtained by the Rietveld refinement method.

PMID- 15582939
TI  - Separation of linear and non-linear imaging components in high-resolution
      transmission electron microscope images.
AB  - Linear and non-linear image components in high-resolution transmission electron
      microscope images were successfully separated by applying a bandpass filter to
      the three-dimensional Fourier spectrum of its through-focus series of images. In
      the observed lattice image of a wedgeshaped Si [110] crystal, we determined the
      magnitude of the contribution of the non-linear imaging components to the total
      image intensity distribution. The contribution was proved to become sometimes
      larger than that of the linear imaging component, even at a thickness of 13 nm.

PMID- 15582940
TI  - Influence of plasma and inflammatory proteins on the ultrastructure of exogenous
      surfactant.
AB  - We tested the hypothesis that albumin, fibrinogen and eosinophilic cationic
      protein (ECP) alter not only the function but also the ultrastructural
      composition of natural bovine surfactant (Alveofact). Therefore, natural bovine
      surfactant was mixed with equimolar concentrations of these proteins for 2 h and
      prepared for electron microscopical examination. Volume fractions, the volume to
      surface ratio and the volume-weighted mean volume were determined by using
      various stereological methods. Alveofact surface activity was tested with the
      capillary surfactometer. Native Alveofact-suspension contained mainly
      multilamellar bodies (numerous concentric predominantly fused compact
      phospholipid lamellae) and small fractions of multilamellar vesicles (several
      concentrically arranged lamellae with a less dense order) and unilamellar
      vesicles (one to two concentrically arranged phospholipid lamellae), but no
      tubular myelin. Addition of proteins to Alveofact led to a protein-dependent
      alteration in the distribution patterns of surfactant subtypes. The significant
      highest decrease in the volume fraction of multilamellar bodies was found in
      Alveofact-fibrinogen preparations and the lowest decrease was in Alveofact
      albumin preparations. Interaction of Alveofact with ECP resulted in a significant
      decrease in the size of multilamellar bodies and a significant increase in the
      volume fraction of very small unilamellar and electron-dense vesicles. Alveofact
      with ECP kept test capillaries open for the shortest time, while Alveofact with
      albumin had little inhibitory effect. There was a significant correlation between
      percentage of capillary openness and the volume fraction quotient of inactive to
      active surfactant subtypes. Thus, equimolar concentrations of different proteins
      in Alveofact induce a conversion of multilamellar bodies combined with a decrease
      in surface activity. The most impressive structural alterations were found after
      mixture with ECP.

PMID- 15582941
TI  - Immunohistochemical detection of haem oxygenase in AA amyloidogenesis.
AB  - Haem oxygenase (HO)-1, a rate-limiting enzyme in the degradation of haem, is
      increased in Alzheimer's disease and in inflammations such as AA amyloidosis.
      However, the specific association of HO-1 is poorly understood in AA amyloidosis.
      In this study, we designed the experiment to reveal the contribution and
      association of HO-1 in the spleen during experimental murine AA amyloidosis.
      Experimental murine AA amyloidosis was induced with injection of an emulsion
      consisting of Freund's complete adjuvant and Mycobacterium butyricum. The serum
      amyloid A level was highest on day 3. The distribution of cells containing iron,
      indicating an increase of HO-1 in the red pulp, was detected with Berlin blue
      staining. AA amyloid formation was immunohistochemically detected as a marker by
      chondroitin sulphate proteoglycan (CSPG), one of the components of AA amyloid
      fibrils. Immunolocalizations of HO-1 and CSPG indicated a conspicuous increase
      and scattering of positive cells in the red pulp of the spleen. Double positive
      cells were not detected. On day 7, amyloid deposition was detected with Congo red
      staining in the extracellular spaces in the marginal zone of the white pulp in
      the spleen and HO-1-positive cells accumulated near the amyloid deposition area.
      CSPG was detected within the cells and also localized in the amyloid deposition
      area. CSPG was still not localized in the HO-1-positive cells. Double positive
      cells of HO-1 and CSPG were localized in the red pulp and in the amyloid
      deposition area on day 14. X-ray microanalysis indicated the existence of iron in
      the electron-dense bodies of fibroblasts in the amyloid deposition areas. The
      fibroblasts extended amyloid fibrils into the extracellular spaces of the
      marginal zone. These results suggest that HO-1-positive fibroblasts, but not HO-1
      positive macrophages, are associated with the late stage of amyloid fibril
      formation.

PMID- 15582942
TI  - Appearance of electron-dense segments: indication of possible conformational
      changes of pre-mineralizing collagen fibrils in the osteoid of rat bones.
AB  - To elucidate precise mechanisms of appositional mineralization of bone,
      structural features of mineralizing collagen fibrils of the osteoid in normal and
      hypocalcaemic rats were examined in detail by transmission electron microscopy.
      Ultrathin sections of the osteoid of various types of bones of the rats fed with
      regular or normal calcium diet often displayed electrondense segments in the
      specific regions of the collagen fibrils located immediately adjacent to the
      mineralization front or to the mineralization nodules. Such dense segments
      appeared only after Ur-Pb staining and were more distinct in undecalcified
      specimens. Dense segments were undetectable in ultrathin sections picked up on
      ethylene glycol instead of water in the trough, even after Ur-Pb staining.
      Collagen fibrils in the widened osteoid of hypocalcaemic rats fed with calcium
      free diet failed to show electron-dense segments. A careful comparison between
      the hydrously or anhydrously processed adjacent sections of a normal rat bone
      indicated a drastic dissolution of electron-dense material from the bone matrix
      near the mineralization front in hydrously processed sections and, thus,
      implicated the presence of labile mineral-matrix complexes in the recently
      mineralized bone matrix. Such labile sediments were readily dissociated within
      the ultrathin sections while the sections were floating on water and immediately
      adsorbed onto the pre-mineralizing collagen fibrils, where some conformational
      changes might have occurred. These data indicate that highly electron-dense
      segments appearing in the osteoidal collagen fibrils are a type of process
      induced product, which indirectly represent possible structural alterations in
      the segmental portions of pre-mineralizing collagen fibrils in the osteoid of rat
      bones.

PMID- 15582943
TI  - Cytochemical detection of endogenous peroxidase in the intralobular ducts of
      hamster major salivary glands.
AB  - Light and electron microscopic cytochemical investigation of endogenous
      peroxidase activity in the intralobular ducts of hamster major salivary glands
      was carried out using the diaminobenzidine-hydrogen peroxidase method. The
      peroxidase reaction product was localized in the nuclear envelope, the cisternae
      of the endoplasmic reticulum, the Golgi apparatus and secretory granules in both
      the intercalated duct cells and the striated duct light cells of all glands.
      These results suggest the ability of the intralobular duct cells to secrete
      peroxidase the same as that of acinar cells in hamster salivary glands.

PMID- 15582945
TI  - Improvements in performance of focused ion beam cross-sectioning: aspects of ion
      sample interaction.
AB  - A gallium (Ga) focused ion beam (FIB) has been applied increasingly to 'site
      specific' preparation of cross-sectional samples for transmission electron
      microscopy (TEM), scanning TEM, scanning electron microscopy and scanning ion
      microscopy. It is absolutely required for FIB cross-sectioning to prepare higher
      quality samples in a shorter time without sacrificing the site specificity. The
      present paper clarifies the parameters that impose limitation on the following
      performances of the FIB cross-sectioning: milling rate, cross-sectioning at a
      right angle with respect to the sample surface, curtain structures formed on the
      cross sections, ion implantation and ion damage. All of these are discussed from
      the viewpoint of ion-sample interaction. Improvements for these performances
      achieved by diminishing their limiting origins or by correcting the resultants
      are described. Especially, the FIB scanning speed is significantly utilizable to
      improve the milling rate. A microsampling method, which allows the FIB incidence
      in a sidewards or upwards direction as well as downwards with respect to the
      microsample surface, is very effective to minimize the curtain structures.

PMID- 15582946
TI  - Reducing focused ion beam damage to transmission electron microscopy samples.
AB  - One of the most important applications of focused ion beam (FIB) systems is
      sample preparation for transmission electron microscopy (TEM). However, the use
      of the FIB inherently involves changing and damaging the sample, and thereby
      degrades the TEM resolution. This paper addresses the beam-induced damage and
      artifacts, particularly in applications involving silicon semiconductors. The
      damage appears in the form of amorphization on the surface of the TEM foil. The
      characteristics of this amorphous damage were studied by making TEM observations
      of cross sections of the affected foil. The damage is typically 20 to 30 nm thick
      for a 30 keV FIB, which is generally overly thick for modern silicon devices with
      feature sizes less than 250 nm. This paper reviews the reported damage depths of
      FIB-prepared samples, which are determined by experiments and calculations.
      Several damage reduction techniques, such as the use of gas-assisted etching, low
      energy FIB, cleaning the FIBfabricated cross section by wet or dry etching and
      cleaning by broad ion beam (BIB) milling have also been reviewed, with emphasis
      on applicability to silicon devices. We conclude that the use of low energy FIB
      and cleaning by argon BIB are particularly efficient techniques.

PMID- 15582947
TI  - Evaluation of TEM samples of an Mg-Al alloy prepared using FIB milling at the
      operating voltages of 10 kV and 40 kV.
AB  - Transmission electron microscopy (TEM) samples of an Mg-Al alloy has been
      prepared using a Ga-focused ion beam (FIB) milling at two different operating
      voltages of 10 kV and 40 kV to investigate the influence of the FIB energy on the
      sample quality. The fine structures of the samples have been studied using a high
      resolution TEM, and the concentration of the implanted Ga was analysed using an
      energy dispersive X-ray (EDX) analysis. The result of the TEM observation
      revealed that point defects were introduced to the sample finally milled at 40 kV
      but not at 10 kV. However, crystal lattice images and electron diffraction
      patterns were clearly observed on both the samples. The typical influence of the
      FIB energy was indicated in the elemental analysis. The relative Ga concentration
      in the thin sample finally milled at 10 kV was 1.0-2.0 at% that is less than half
      of 4.0-6.0 at% of the Ga concentration in the sample finally milled at 40 kV. A
      comparison between the experimental results of the Ga concentration measurement
      with simulation was also discussed.

PMID- 15582948
TI  - Application of focused ion beam techniques and transmission electron microscopy
      to thin-film transistor failure analysis.
AB  - The locations of process-induced defects in hydrogenated amorphous silicon thin
      film transistors (a-Si:H TFTs), which are used as elements of active-matrix
      liquid crystal displays, were investigated by combining focused ion beam
      techniques with cross-sectional transmission electron microscopy (X-TEM). The FIB
      technique is applied to TFT failure analysis problems, which require considerable
      localised etching without inducing mechanical stress or damage at fragile failure
      locations. We demonstrate the manner in which these techniques are used to
      characterise TFT defects such as pinholes and portions of the multilayer damaged
      by mechanical stress. A dramatic improvement brought about by the FIB technique
      is the increase in temporal efficiency of sample preparations. X-TEM observations
      also lead to identification of the fault and analysis of its cause, which in turn
      lead to a marked yield improvement.

PMID- 15582949
TI  - A study of the damage on FIB-prepared TEM samples of AlxGa1-xAs.
AB  - The damage produced by focused ion beam (FIB) milling on a TEM sample of AlGaAs
      crystals has been studied. The damage observed on the sidewall of an AlGaAs
      transmission electron microscopy (TEM) sample was an amorphous layer. The
      thickness of the amorphous layer linearly increased with an increase in FIB
      accelerating voltage from 5 to 30 kV. The thickness of the amorphous layer of
      Al(x)Ga(1-x)As was constant at 3 nm and was independent of the Al concentration x
      when the accelerating voltage was below 5 kV. The thickness of the amorphous
      layer of Al(x)Ga(1-x)As decreased with an increase in Al concentration x when the
      accelerating voltage was above 5 kV. FIB milling at 5 kV effectively minimizes
      the thickness of the amorphous layer and also provides flat sidewalls on
      multilayer samples of Al(x)Ga(1-x)As that are prepared for TEM and scanning
      electron microscopy (SEM).

PMID- 15582950
TI  - A new FIB fabrication method for micropillar specimens for three-dimensional
      observation using scanning transmission electron microscopy.
AB  - A new method to prepare micropillar specimens with a high aspect ratio that is
      suitable for three-dimensional scanning transmission electron microscopy (3D
      STEM) was developed. The key features of the micropillar fabrication are: first,
      microsampling to extract a small piece including the structure of interest in an
      IC chip, and second, an ion-beam with an incident direction of 60 degrees to the
      pillar's axis that enables the parallel sidewalls of the pillar to be produced
      with a high aspect ratio. A memory-cell structure (length: 6 microm; width: 300 x
      500 nm) was fabricated in the micropillar and observed from various directions
      with a 3D-STEM. A planiform capacitor covered with granular surfaces and a solid
      crossing gate and metal lines was successfully observed threedimensionally at a
      resolution of approximately 5 nm.

PMID- 15582951
TI  - Transmission electron microscopy on thin film of high density magnetic composite
      prepared by FIB method.
AB  - A thin specimen of a high density magnetic composite (HDMC), which is a type of
      powder magnetic cores was prepared for transmission electron microscopy (TEM)
      using a focused ion beam (FIB) method. A homogeneous thin film containing an
      insulator boundary between the constituent Fe powders was obtained successfully.
      Using this thin film, detailed flow of magnetic flux was visualized by electron
      holography, and the magnetic flux density was estimated to be 1.73 +/- 0.09 T
      being consistent with that of a bulk HDMC (1.70 T). Moreover, through Lorentz
      microscopy, the characteristic magnetization process of HDMC was observed by
      applying the magnetic field up to approximately 8 kA/m.

PMID- 15582952
TI  - Side-milling technique of preparing device cross-sections for electron holography
      based on a focused ion beam micro-sampling system.
AB  - A new milling technique based on a focused ion beam (FIB) microsampling system is
      proposed to avoid the curtaining effect, commonly occurring in other FIB milling
      methods, in order to obtain a crosssectional device specimen with uniform
      thickness can be obtained for electron holographic observation.

PMID- 15582953
TI  - Post-thinning technique for a lifted-out membrane.
AB  - A novel technique for post-thinning of lifted-out membranes already mounted on a
      mesh was developed using a Ga(+) ion beam at an accelerating voltage of 5 kV. It
      was applied to the preparation of transmission electron microscopy specimens from
      a selected cell of a silicon dynamic random-access memory.

PMID- 15582954
TI  - Specimen preparation for high-resolution transmission electron microscopy using
      focused ion beam and Ar ion milling.
AB  - We have developed a focused ion beam (FIB)-Ar ion-milling technique for high
      resolution transmission electron microscopy. A micrometresized specimen was
      mounted on a cross section of metal foil of a few micrometres thick, using FIB
      microsampling. Following this, a 2 degrees wedgeshaped part was made in the
      specimen using FIB. Finally, the specimen was milled using an Ar ion beam to
      remove the FIB-damaged layers. We applied the FIB-Ar ion milling technique to a
      CeO(2)/Gd(2)Zr(2)O(7) multilayer specimen, resulting in the crystal lattice
      fringes of both layers being clearly observable in comparison to a specimen
      finished using a Ga ion beam at an accelerating voltage of 10 kV.

PMID- 15582955
TI  - A new method for preparing plan-view TEM specimen of multilayered films using
      focused ion beam.
AB  - A new method is proposed for preparing plan-view specimens of a
      CeO(2)/Gd(2)Zr(2)O(7) multilayer on a metal substrate using focused ion beam
      milling. In the plan-view specimen, a membrane from the surface region of the
      CeO(2) to the Gd(2)Zr(2)O(7) layer was thinned to electron transparence so that
      the entire span of the multilayer can be observed in a single sample. The in
      plane alignments of the CeO(2) layer and the Gd(2)Zr(2)O(7) layer were analysed
      using selected-area diffraction patterns (SADPs). The boundaries between the
      CeO(2) grains were also examined using SADPs.

PMID- 15582956
TI  - HVEM study of crack-tip dislocations in Si crystals prepared by FIB and twin
      blade cutting method.
AB  - Crack-tip dislocations in silicon crystals have been examined by using high
      voltage electron microscopy. Cracks were introduced by the Vickers indentation
      method at room temperature and the indented specimens were annealed at high
      temperatures to induce dislocations around crack tips under the presence of
      residual stress due to the indentation. A selected area around a crack tip was
      thinned by a focused ion beam (FIB) technique. Specimens were thinned in advance
      by a twin-blade cutting (TBC) method, which is a simple cutting process for
      saving FIB machine time. A combination of FIB and TBC can be a useful thinning
      procedure for the efficient preparation of transmission electron microscopy
      specimens. Characteristic dislocation structures were observed around the tip of
      a crack, aiding the elucidation of dislocation processes, which is essential to
      increase the fracture toughness of materials.

PMID- 15582957
TI  - 3D analysis of cracking behaviour under indentation in ion-irradiated beta-SiC.
AB  - To provide a microstructural basis for evaluating fracture toughness by an
      indentation test, a new method to analyse three-dimensional (3D) cracking
      behaviour in beta-SiC is developed. As an example, the effect of ion irradiation
      on crack propagation was studied. The sequential cutting-out of thinned sections
      by focused ion beam (FIB) processing around an indentation impression enabled the
      reconstruction of the 3D behaviour of cracking near the indentation impression.
      The FIB processing has an advantage in making finely polished thin sections for
      scanning electron microscopy (SEM)/transmission electron microscopy without
      damaging the structure near cracks. In the present work, the procedure of cross
      sectioning and the results of crack propagation analysis in beta-SiC by SEM
      inspection are described.

PMID- 15582958
TI  - Microstructural analysis of the deformation range under nano-indentation in beta
      SiC.
AB  - As a powerful tool to analyse microstructural evolution under irradiation and the
      interaction of moving dislocations with radiation-induced defects, a focused ion
      beam (FIB) method was applied to ion-irradiated SiC followed by the nano
      indentation test. An FIB method has excellent capability to prepare thin foils
      from the area of interest with a high accuracy of location and wide flexibility
      in the sampling direction. These advantages are demonstrated in the application
      to Si ion-irradiated SiC by transmission electron microscope observation.

PMID- 15582959
TI  - Application of FIB with micro pick-up to microstructural study of irradiated
      SiC/SiC composites.
AB  - The combination of focused ion beam (FIB) micro-processing and the lift-out
      technique using the micro pick-up system was applied to the preparation of TEM
      specimens of irradiated SiC/SiC composites. The deformation caused by
      microstructural evolution was observed in the pyrolitic carbon interphase, and
      several helium bubbles and cavities were detected in the CVI matrix.

PMID- 15582960
TI  - Focused ion beam fabrication of field-ion microscope specimens from mechanically
      milled pearlitic steel powder.
AB  - Sharp needle-like specimens for atom-probe field-ion microscope (APFIM) analysis
      have been prepared successfully from mechanically milled pearlitic steel powders.
      Mechanically milled powders were packed in a stainless steel tube with carbonyl
      steel powders and then consolidated by sheath cold-rolling to obtain a bulk
      composite. A small square rod was cut out from the bulk and electropolished to a
      blunt needle. It was then fabricated to a nanometre-sized needle by a focused ion
      beam technique using an annular gallium ion beam. The tip radius of the specimen
      was <50 nm, which is suitable for use in APFIM.

PMID- 15582961
TI  - A review of focused ion beam technology and its applications in transmission
      electron microscopy.
AB  - The role of focused ion beam (FIB) fabrication in the development of sample
      preparation techniques for transmission electron microscopy (TEM) has been
      described in this paper. Since the repeatability of FIB sampling and TEM
      observations has become important, the microsampling and in situ lift-out methods
      are currently in wide use. Furthermore, artifacts induced during FIB milling and
      the consequent difficulties with energy dispersive X-ray spectroscopy are
      detailed. The remarkably increased capability of scanning ion microscopy and its
      applications are also discussed.

PMID- 15582962
TI  - Application of FIB microsampling technique to long-period ordered TiAl single
      crystal with composition gradient.
AB  - Metastable long-period superstructures in an L10-TiAl single crystal with a
      composition gradient were observed successfully by transmission electron
      microscopy with a focused ion beam (FIB) microsampling technique. The composition
      gradient from 54.7 to 75 at.% Al with approximately 6 microm width was detected
      by electron probe microanalysis and foil specimens containing the composition
      gradient area were fabricated by the FIB microsampling method. The foil specimens
      clearly exhibit sequential changes in long-period superstructure depending on the
      Al concentration.

PMID- 15582963
TI  - FIB and TEM observations of defects in hot-dip zinc coatings.
AB  - The characteristic ability of FIB (focused ion beam) fabrication to remove
      materials from a very small and/or precisely located slab using an accelerated Ga
      ion beam were employed to prepare cross-sectional thin films of zinc-coated steel
      sheets composed of Fe-Zn intermetallic compounds. A few defects observed
      frequently on the galvannealed (GA) coating surface were analyzed. Streaky marks
      indicated the rich concentration of oxides at the interface between the
      galvannealed coating and the steel substrate. The annealing experiment indicated
      the existence of Mn and Si oxides on the steel substrate. The grain size of
      ferrite in the extreme surface of the substrate was smaller as compared with
      conventional IF (Interstitial Free) steels. Furthermore, some superlattice spots
      were observed at the fine ferrite grain. Defects that are termed 'wavy pattern'
      and 'dross' were also analyzed by the combination of the FIB and TEM
      (Transmission Electron Microscope) techniques.

PMID- 15582964
TI  - Plan-view and cross-sectional characterization of thiourea-treated phosphorus
      added steel surface.
AB  - The galvanizing reaction is retarded when phosphorus-added steel is used as a
      substrate. We have found that both the galvanizing and the galvannealing
      reactions are highly promoted when thiourea solution is coated on the cold-rolled
      steel surface before the annealing process. Both a plan-view and cross-sectional
      characterization of thiourea-coated steel was performed using low-voltage
      scanning electron microscopy and a focused ion beam. A fine grain structure is
      formed in the surface region of approximately 1 microm in thickness. In this
      region, (Mn, Fe)S particles are formed by the reaction between sulphur from
      thiourea and manganese from steel. These (Mn, Fe)S particles have a pinning
      effect on the cold-rolled steel grains and greatly retard recrystallization when
      the steel is annealed. It is concluded that the promotion of the galvannealing
      reaction is due to the increased diffusion paths of zinc and iron materialized by
      the fine grain structure of the thiourea-coated steel.

PMID- 15582965
TI  - Microstructures of galvannealing coats plated on an iron substrate deformed by
      indentation.
AB  - Two different galvannealed (GA) steels with different formability performances
      were deformed at room temperature with a micro-Vickers indenter. Cross-sectional
      specimens for transmission electron microscopy were prepared from the indented
      areas using a focused ion beam technique. Direct evidence of plastic deformation
      of the GA coats was obtained. Cracks were observed to nucleate at triple points
      of two neighbouring Gamma and substrate Fe. The GA coat with better formability
      has finer grains than the GA coat, with worse formability.

PMID- 15582966
TI  - Application of a FIB-STEM system for 3D observation of a resin-embedded yeast
      cell.
AB  - The combination of a focused ion beam (FIB) system and a scanning transmission
      electron microscope (STEM) has been applied to the three-dimensional (3D)
      observation of a resin-embedded yeast cell. Using a FIB microsampling technique,
      a sample with a thickness of tens of micrometres was extracted from a resin
      embedded block sample. The extracted sample was transferred to a FIB-STEM
      compatible specimen rotation holder and trimmed by FIB milling for 3D STEM
      observation. Although the FIB milling was carried out at an operating voltage of
      40 KV, the sample was cross sectioned without forming a harmful damage layer on
      its surface. Cell structures, such as cell wall, cell membrane, mitochondria,
      peroxisomes, endoplasmic reticulum and vacuoles, were observed clearly in a
      pillar-shaped sample of 20 microm long, 4 microm wide and 3 microm deep.

PMID- 15582967
TI  - Microsampling technique for EBSP inspection on the cross-sections of copper
      trench lines in ULSIs.
AB  - The crystal microstructure of copper interconnects in ultra large scale
      integrations (ULSIs), depends on factors such as the trench line width and
      patterns. Therefore, inner crystal characterisation of the desired trench lines
      composed of copper is required. Electron backscatter diffraction pattern (EBSP)
      inspection has become a powerful technique for analysing the crystal
      characterisation of interconnects. However, EBSP inspection is sensitive to
      surface conditions such as contamination and strain. In this study, we applied
      the focused ion beam (FIB) technology, particularly, the microsampling technique
      to the preparation of samples for EBSP inspection on the cross-sections of the
      copper trench lines. As a result, we demonstrate that a damaged layer composed of
      a crystalline substance is formed on the plane of the copper as revealed by the
      30 kV Ga(+) FIB milling, but an EBSP signal is detectable. In conclusion, the
      cross-sectional sample preparation technique employing microsampling is found to
      be very powerful for analysing the inner crystal characteristics of the desired
      copper trench lines by EBSP inspection.

PMID- 15582968
TI  - Crystallographic orientation contrast associated with Ga+ ion channelling for Fe
      and Cu in focused ion beam method.
AB  - In this study, Cu and Fe single crystals are used to examine the change in
      secondary electron intensity associated with Ga(+) ion channelling in a focused
      ion beam (FIB) system. The single crystals having three different orientations
      are tilted with respect to the beam incidence and the resulting variation in the
      secondary electron intensity is measured through the variation in brightness of
      the crystals. It is shown that intensity minima appear at the beam directions
      normal to the lower indices of the crystal orientations. The appearance of the
      intensity minima including the magnitude of the minima is consistent with the
      prediction based on the event of ion channelling in the crystal and is affected
      by the crystal structure. The effect of background on the intensity minima is
      discussed in this study. It is suggested that the presence of the intensity
      minima may be used to identify a crystal orientation including a crystal
      structure.

PMID- 15582969
TI  - Direct observation of electrostatic microfields by four-electron-wave
      interference using two electron biprisms.
AB  - A new method has been developed for directly visualizing electromagnetic
      microfields in real time by the interference of four-electron waves obtained
      using a transmission electron microscope equipped with a field-emission gun and
      two electron biprisms. When one object wave and three reference waves interfere,
      equal-phase lines of the object wave are displayed as the intensity modulation of
      the interference fringes, in the manner same as in the three-electron-wave
      interference. The advantage of the four-electron-wave interference is that equal
      phase lines are observed without precisely adjusting the angle between the two
      biprisms or rigorously controlling the fringe spacings of the two biprisms.

PMID- 15582970
TI  - A method for multidirectional TEM observation of a specific site at atomic
      resolution.
AB  - A new technique has been developed for the three-dimensional structure
      characterisation of a specific site at atomic resolution. In this technique, a
      focused ion beam (FIB) system is used to extract a specimen from a desired site
      as well as to fabricate the electron transparent specimen. A specimen holder with
      a specimen stage rotation mechanism has also been developed for use with both an
      FIB system and a high-resolution transmission electron microscope (TEM). The
      specimen holder allows both the FIB milling of a specimen and its observation in
      TEM without remounting the specimen from the specimen holder. A specimen for the
      three-dimensional TEM observation is extracted using the FIB micro-sampling
      technique and shaped into a pillar to mount on a tip of a needle stub enabling a
      multidirectional observation. The technique was applied to the multidirectional
      observation of the crystal structure of an Si single crystal at atomic
      resolution. The crystal lattice fringes of the two Si(111) planes with distances
      of 0.31 nm as well as the lattice fringes of the Si(200) with distances of 0.19
      nm were clearly observed.

PMID- 15582971
TI  - High energy-resolution electron energy-loss spectroscopy study of the electronic
      structures of Li- and Mg-doped alpha-rhombohedral boron.
AB  - Electron-doped alpha-rhombohedral boron (alpha-r-B) crystals were synthesized by
      Li- and Mg-dopings. The doped alpha-r-B particles showed a shiny metallic colour,
      though non-doped alpha-r-B crystals showed a dark red colour (red boron). The
      electronic structures of doped alpha-r-B single crystals were examined by a high
      energy-resolution electron energy-loss spectroscopy microscope. Boron 1s electron
      excitation spectra, which show the density of states of the conduction bands, of
      Li-doped alpha-r-B showed a chemical shift toward a smaller binding-energy side,
      indicating a charge transfer from the doped atoms to alpha-r-B. These spectra
      also showed a sharp intensity increase at the onset with a width of an energy
      resolution of the experiment. The sharp intensity increase may be assigned to a
      Fermi edge produced by the electron doping. The spectra of Mg-doped alpha-r-B
      showed a chemical shift indicating an electron doping, but did not show the
      presence of a Fermi edge.

PMID- 15582972
TI  - Lattice parameter determination of a composition controlled Si1-x Gex layer on a
      Si (001) substrate using convergent-beam electron diffraction.
AB  - The six lattice parameters (a, b, c, alpha, beta and gamma) of Si(1-x)Ge(x),
      which was grown epitaxially on a Si (001) substrate with a varying Ge
      concentration, were determined by convergent-beam electron diffraction (CBED)
      without any assumption of crystal lattice symmetry. It was revealed that the
      lattice parameter c of Si(1-x)Ge(x) varies linearly with the Ge concentration and
      that the lattice symmetry is lowered from cubic to tetragonal, excluding an
      artifact due to the thinning of the specimen. The effect of strain relaxation
      that is caused by thinning specimens is discussed. Ge concentrations of examined
      specimen areas are evaluated using the obtained lattice parameters.

PMID- 15582973
TI  - Practical considerations on the determination of the accuracy of the lattice
      parameters measurements from digital recorded diffractograms.
AB  - The influence of magnification and defocus on the precision Delta d/d of lattice
      parameter measurements have been studied by evaluating the diffraction vector
      length and the signal-to-noise ratio (SNR) of the diffraction peaks in
      diffractograms calculated by fast Fourier transformation (FFT) of digitally
      recorded images. Examples are perfect crystals (Si and SiC) and defective
      crystals (two- and three-dimensional defects within SiC). It is shown that the
      precision is independent of the diffuseness of the FFT reflections caused by
      defocus changes or by two-dimensional defects. For the case of a perfect and/or a
      defective but unstrained crystal, the precision Delta d/d is linearly dependent
      on the diffraction vector length. For optimal conditions, the highest precision
      is 0.002. For a defective crystal containing precipitates (nanocrystals), it was
      found for both the matrix and the nanocrystals that the precision of the
      measurement is determined by the contribution of strain value (Delta d/d)(strain)
      of the defective crystal and accuracy Delta d/d for the perfect matrix crystal.

PMID- 15582974
TI  - HAADF-STEM study on the early stage of precipitation in aged Al-Ag alloys.
AB  - We report on the structure of Ag precipitates in aged Al-Ag alloys using
      transmission electron microscopy and high-angle annular detector darkfield
      scanning transmission electron microscopy (HAADF-STEM). Irregularly shaped small
      Ag particles of 1-2 nm dominate the alloy annealed at 140 degrees C for 10 h.
      These particles are present also within large precipitates (10-50 nm), which are
      often characterized by their {100} and {110} facets. In addition, atomic
      resolution HAADF-STEM images revealed that Ag atoms tend to form {111} planar
      clusters, which criss-cross a colony of the irregularly shaped small Ag
      precipitates.

PMID- 15582975
TI  - Influence of the image quality deterioration of a tilted thick specimen on
      electron tomography.
AB  - In electron tomography (ET) based on a transmission electron microscope, the
      effective thickness of a specimen increases with the tilt angle and, therefore,
      the projection quality may deteriorate because of electron scattering. The
      information-missing region, however, can be reduced by broadening the specimen
      tilt range. To clarify the general influence of these effects on ET, the
      projection quality varying with the tilt angle was quantitatively evaluated for a
      5-microm thick specimen observed with a 3 MV ultrahigh-voltage electron
      microscope. Simulations of three-dimensional reconstruction were then performed
      for different specimen thicknesses and tilt ranges. As a result, the ET accuracy
      was shown to decrease as the specimen thickness increased. However, an optimum
      specimen-tilt range, at which ET could reach its highest accuracy, was found to
      exist and become small with the increase of the specimen thickness. The presented
      results are helpful for determining the specimen thickness limitation on the ET
      resolution and improving the ET fidelity of thick specimens.

PMID- 15582976
TI  - Hornet flight is generated by solar energy: UV irradiation counteracts
      anaesthetic effects.
AB  - The Oriental hornet Vespa orientalis (Hymenoptera, Vespinae) flies outside its
      nest only in the daytime and never in the dark. Oriental hornets can be
      anaesthetized by means of diethyl ether, following which they awake spontaneously
      within about > or =1 h. However, when the anaesthetized hornets are exposed to
      direct irradiation they awake much faster and immediately fly out and this is
      within the temperature range for their normal activities (20-40 degrees C). Light
      exerts an effect not only on intact hornets, but also on their main body parts,
      be they the head, thorax or gaster, or a torso without a head or without a
      gaster. These body parts also 'awake' from ether anaesthesia when illuminated,
      especially by ultraviolet (UV) B or shorter light wavelengths, but a body without
      a gaster awakes much later than normal. As for flight activity, headless hornets
      do not fly at all, while hornets devoid of a gaster flutter their wings when
      illuminated but are incapable of rising in the air. When vespan cuticular regions
      are coated with paint that blocks the passage of light, such as UVB blockers, or
      with white Tipp-Ex, the awakening from anaesthesia is delayed. The vespan cuticle
      evinces photovoltaic activity, even in dead specimens, so that upon exposure to
      light it is possible to record levels of 30-180 mV, both in a wakeful hornet and
      in one that has undergone anaesthesia. We conjecture that in the awake hornet the
      voltage that its cuticle generates under the influence of light is transported
      within the cuticular interlamellar membranes to be utilized as flight energy by
      the muscles attached to them; however, in the narcotized hornet, the diethyl
      ether apparently decreases or disrupts membranal order, blocking any ionic
      channel activity and thereby inducing the anaesthesia. Presumably, this state of
      phase transition is remedied spontaneously, albeit in a lengthy process, or else
      the light energy in UV speeds up restoration of the ionic channel activity and
      the synaptic transmission and thereby contributes to a more rapid awakening. In
      this regard, the hornet gaster is an extensive region for absorbing light, which
      explains why its absence considerably delays the awakening from anaesthesia.

PMID- 15582977
TI  - Modification of physicochemical properties of actin filaments suppresses cell
      fragmentation in the execution phase of staurosporine-induced apoptotic
      processes.
AB  - Effects of jasplakinolide (JSP), a stabilizer of F-actin, and latrunculin A
      (LTA), a destabilizer of F-actin, on a series of events occurring in the
      execution phase of staurosporine (STS)-induced apoptotic processes were studied
      using human osteosarcoma 143B cells. Time-dependent apparent increases of the
      population of cells with collapsed membrane potential of mitochondria (Delta
      Psi(m)) caused by STS treatment were not due to actual decreases in the Delta
      Psi(m) per cell, but due to the fragmentation of cells resulting in decreases in
      the number of active mitochondria per cell. Decreases in the Delta Psi(m) in
      fragmented cells occurred late in the execution phase. Both JSP and LAT failed to
      prevent STS-induced release of cytochrome c from mitochondria followed by the
      activation of caspases 3 and 9, the cleavage of poly (ADP-ribose) polymerase
      (PARP) and apoptotic nuclear fragmentation. However, both drugs prevented STS
      induced apoptotic cell fragmentation and decreases in the Delta Psi(m). These
      results indicate that physicochemical states of actin filaments play a certain
      role in the execution phase of STS-induced apoptotic processes.

PMID- 15582978
TI  - Yellow pigment granules in hornets: their origin and development.
AB  - The present article discusses the yellow pigment in the cuticle of the Oriental
      hornet Vespa orientalis (Vespinae, Hymenoptera). This insect possesses, both in
      its gaster region and its head plates, yellow pigment granules that are located
      underneath the upper layers of the cuticle. All other regions of its body are
      endowed with a colour ranging from brown to black. As for the yellow granules,
      some occur within cells while others bud off from the cells inside tubular
      extensions that interpenetrate the cuticular layers and create accumulations of
      pigment. Whichever the case, the yellow granules invariably are approximately 0.5
      microm in diameter and arranged in three longitudinally extending concentric
      cylinders, with the innermost cylinder comprising a string that interconnects
      between the various granules. Our paper discusses the physical properties of
      these yellow granules and their possible role in everyday hornet life.

PMID- 15582979
TI  - Changes in physicochemical properties of microtubules lead to the formation of a
      single spherical structure of mitochondrial assembly enveloping nuclear
      chromatins.
AB  - Treatment of 143B cells with microtubule-active drugs (MADs) including taxol,
      nocodazole and colchicine induced distinct structural changes, such as rounding
      of the cells with perinuclear clustering of mitochondria, when the cells were
      treated for up to 10 h. When the incubation time with MADs was longer than 10 h,
      multinuclear cells appeared, and their population increased with time. In this
      study perinuclear clustering of mitochondria i.e. mitochondria encircling the
      aggregated chromatin of the nucleus that had lost the nuclear membrane was
      detected. This observation was distinct from that reported in the literature.
      Mitochondria were aligned in a few lines; the occurrence of mitochondria in even
      a single line is an extreme case, resulting in one plane of section for electron
      microscopy. Three-dimensional reconstructions of confocal microscopic images of
      mitochondria revealed that they were assembled as a spherical structure. The
      majority of the cells with perinuclear clustering of mitochondria remained intact
      for up to 24 h. Mitochondria were observed to be clustered around the nucleus in
      the orthodox configuration or in some cases they were moderately condensed, as
      observed electron microscopically. Annexin V and PI double staining of cells
      showed that more than 90% of cells were viable. In the case of treatment with
      taxol, membrane potential of mitochondria per cell was well maintained although
      it was moderately lowered in the case of treatment with nocodazole. Taking into
      consideration the previous data reported from our laboratory, the present results
      may assist in elucidation of the behaviour of mitochondria during the dividing
      processes of mammalian cells, which is yet to be clarified.

PMID- 15582980
TI  - The position and morphology of honeycombs in normal skeletal muscle fibres of the
      healthy frog.
AB  - Honeycombs are regularly arranged networks of tubules in continuity with the T
      system of the skeletal muscle fibre. Their occurrence is usually described in
      pathologically modified or cultivated muscle fibres. Here we describe the
      occurrence of honeycombs in macroscopic normal muscle fibres of healthy frogs. We
      characterize their light- and electronmicroscopic features and represent their
      relationships to motor end plates, fibre nuclei and myofibrils. In these normal
      muscle fibres of healthy frogs, the honeycombs are connected to subsynaptic folds
      and the T-system. Their regional occurrence is discussed with respect to regional
      differences in the regulation of the membrane metabolism. Since we can
      demonstrate them in healthy animals, we do not see any basis why their occurrence
      should be related to pathological modifications of the muscle fibre.

PMID- 15582981
TI  - Simple plunge freezing applied to plant tissues for capturing the ultrastructure
      close to the living state.
AB  - In order to observe the ultrastructure close to the living state, simple plunge
      freezing in liquid propane was applied to plant tissues. The method yielded a
      well-preserved ultrastructure to a depth of up to 40 microm from the surface of
      the young pea leaves, which were used as the specimen. Within the well-frozen
      area all membranes appeared smooth and the ultrastructural details of each
      organelle were similar to those obtained by high-pressure freezing. Several
      physical connections between the membranes were visualized. The relative
      simplicity and the satisfactory freezing performance of the method render it
      suitable for capturing the features of actively functioning cells in routine
      ultrastructural studies.

PMID- 15582982
TI  - Mammalian defensins: structures and mechanism of antibiotic activity.
AB  - Antibiotic peptides are important effector molecules in host-parasite
      interactions throughout the living world. In vertebrates, they function in first
      line host defense by antagonizing a wide range of microbes including bacteria,
      fungi, and enveloped viruses. The antibiotic activity is thought to be based on
      their cationic, amphipathic nature, which enables the peptides to impair vital
      membrane functions. Molecular details for such activities have been elaborated
      with model membranes; however, there is increasing evidence that these models may
      not reflect the complex processes involved in the killing of microbes. For
      example, the overall killing activity of the bacterial peptide antibiotic nisin
      is composed of independent activities such as the formation of target-mediated
      pores, inhibition of cell-wall biosynthesis, formation of nontargeted pores, and
      induction of autolysis. We studied the molecular modes of action of human defense
      peptides and tried to determine whether they impair membrane functions primarily
      and whether additional antibiotic activities may be found. We compared killing
      kinetics, solute efflux kinetics, membrane-depolarization assays, and
      macromolecular biosynthesis assays and used several strains of Gram-positive
      cocci as test strains. We found that membrane depolarization contributes to rapid
      killing of a significant fraction of target cells within a bacterial culture.
      However, substantial subpopulations appear to survive the primary effects on the
      membrane. Depending on individual strains and species and peptide concentrations,
      such subpopulations may resume growth or be killed through additional activities
      of the peptides. Such activities can include the activation of cell-wall lytic
      enzymes, which appears of particular importance for killing of staphylococcal
      strains.

PMID- 15582983
TI  - Neutrophils and keratinocytes in innate immunity--cooperative actions to provide
      antimicrobial defense at the right time and place.
AB  - The human neutrophil is a professional phagocyte of fundamental importance for
      defense against microorganisms, as witnessed by the life-threatening infections
      occurring in patients with neutropenia or with defects that result in decreased
      microbicidal activity of the neutrophil. Likewise, the skin and mucosal surfaces
      provide important barriers against infections. Traditionally, these major defense
      systems, the epithelial cells and the neutrophils, have been viewed as limited in
      their armory: The epithelial cells provide defense by constituting a physical
      barrier, and the neutrophils provide instant delivery of preformed antimicrobial
      substances or on-the-spot assembly of the multicomponent reduced nicotinamide
      adenine dinucleotide phosphate oxidase from stored components for the generation
      of reactive oxygen metabolites. Recent research has shown that epithelial cells
      are highly dynamic and able to generate antimicrobial peptides in response not
      only to microbial infection itself but more importantly, to the growth factors
      that are called into play when the physical barrier is broken, and the risk of
      microbial infection is imminent. Likewise, the neutrophil changes its profile of
      actively transcribed genes when it diapedeses into wounded skin. This results in
      generation of signaling molecules, some of which support the growth and
      antimicrobial potential of keratinocytes and epithelial cells. This paper will
      highlight some recent advances in this field.

PMID- 15582984
TI  - Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic
      lymphocytic leukemia cells.
AB  - Immunostimulatory oligodeoxynucleotides (IS ODN) can mediate a number of
      immunologic effects. We previously demonstrated that treatment of B cell chronic
      lymphocytic leukemia (B-CLL) cells with one class of IS ODN, CpG ODN, alters
      their phenotype and increases their immunogenicity. Here, we demonstrate that in
      contrast to the classic understanding of CpG ODN as inhibitors of B cell
      apoptosis, IS ODN including CpG ODN induce apoptosis in B-CLL cells. It is
      important that these changes are seen not only with CpG ODN but with ODN that
      lack the classical CpG motif. B-CLL cells from 20 subjects were treated in vitro
      with IS ODN for up to 7 days. IS ODN treatment resulted in increased numbers of
      apoptotic cells in 13 out of 20 B-CLL samples. IS ODN enhanced apoptosis in
      samples with 13q deletion as a single aberration and had a heterogeneous effect
      on apoptosis in samples with other aberrations including 17p deletion, 11q
      deletion, or trisomy 12. Induction of apoptosis did not correlate with expression
      of the CpG ODN receptor Toll-like receptor 9. Apoptosis was dependent on the
      activation of caspases and was accompanied by up-regulation of CD95/Fas and its
      ligand. We conclude that IS ODN including CpG ODN can induce apoptosis of most B
      CLL samples. The ability of IS ODN to induce apoptosis differs based on
      cytogenetic status. Up-regulation of CD95/Fas may play a role in IS ODN-induced
      apoptosis of B-CLL.

PMID- 15582985
TI  - Alcohol consumption and midlife cognitive change in the British 1946 birth cohort
      study.
AB  - AIMS: Cross-sectional studies suggest that alcohol consumption benefits cognitive
      function. However, more longitudinal studies are required to confirm that alcohol
      has an effect on cognitive change and to rule out the possibility that those of
      higher ability engage in a lifestyle that protects against cognitive decline.
      METHODS: We investigated the association between self-reported alcohol
      consumption and change in memory, speed and concentration in midlife, in 903 men
      and 861 women enrolled in the MRC National Survey of Health and Development (the
      British 1946 birth cohort). RESULTS: After controlling for educational
      attainment, occupational social class and general cognitive ability, it was found
      that alcohol consumption was associated with a slower memory decline from 43 to
      53 years in men, but a more rapid decline in visual search speed for the same
      interval in women. These effects were not explained by a further control for
      health status (body water weight, smoking, exercise, cardio-respiratory disease
      and affective state). CONCLUSIONS: Our data suggest that alcohol consumption is
      associated with a slower memory decline. However, the negative association
      between alcohol and psychomotor function in women is a potential cause for
      concern.

PMID- 15582986
TI  - Drinking patterns and perspectives on alcohol policy: results from two Ontario
      surveys.
AB  - AIMS: Previous research has shown that heavier drinkers, in comparison to light
      drinkers or abstainers, are more likely to favour increased access to alcohol and
      relaxation of control policies. Often, studies have not examined whether
      attitudes to alcohol policies vary according to a respondent's pattern of
      drinking. This study examined the association between drinking variables and
      views on policy, using six drinking variables and six topics on alcohol policy.
      METHODS: Data were available from two Ontario surveys conducted in 2000 and 2002,
      which took representative samples of adults, aged 18 and older, selected by
      random digit dialling, who participated in interviews over the telephone (n =
      1294 and 1206, respectively). Drinking variables include drinking status,
      drinking frequency, usual number of drinks, typical weekly volume, frequency of
      5+ drinks per occasion and Alcohol Use Disorders Identification Test (AUDIT)
      scores. Six policy items were examined: alcohol taxes, warning labels, density of
      retail alcohol outlets, privatization of government liquor stores, alcohol
      advertising and consultation with health experts on decisions on alcohol policy.
      Logistic regression analyses included five demographic variables: gender, age,
      marital status, education and income. RESULTS: Among males, there was strong
      support for increased access to alcohol and fewer controls over alcohol policies.
      This relationship, although not as strong, also emerged for frequent consumers,
      high volume drinkers and those with a higher AUDIT score. CONCLUSION: Whether it
      is intentional or not, government policies that tend to make alcohol more
      available cater to young, heavy-drinking males who possibly experience problems
      in connection with their drinking behaviour.

PMID- 15582987
TI  - Developing a willingness to change: treatment-seeking processes for people with
      alcohol problems.
AB  - AIMS: The study explores treatment-seeking processes in men and women with
      alcohol problems, focusing on promoting and hindering factors. METHODS: Open
      interviews were held with five women and seven men within a month of their first
      voluntary treatment for alcohol problems. The interview protocols were analysed
      consecutively in accordance with grounded theory methodology. RESULTS: Developing
      a willingness to change was found to be the basic psychosocial process that lead
      to treatment-seeking. Categories that constituted sub-processes and supported
      willingness to change were: (i) actuating inner forces; (ii) dealing with
      conflicting feelings and thoughts; and (iii) hoping to turn the situation around.
      These processes were continuously assisted by demanding and caring support from
      partners, friends or professionals. CONCLUSIONS: The processes that precede
      treatment-seeking were highly complex, and both internal and external factors
      promoted and hindered treatment entry. The social significance of alcohol and the
      grief related to thoughts of abstaining were the most striking hindering factors.
      Such feelings need to be considered when motivating people to seek treatment for
      alcohol problems.

PMID- 15582988
TI  - Suppressing effect of the cannabinoid CB1 receptor antagonist, SR147778, on
      alcohol intake and motivational properties of alcohol in alcohol-preferring sP
      rats.
AB  - AIMS: The present study investigated the effect of the newly synthesized
      cannabinoid CB(1) receptor antagonist, SR147778, on alcohol intake and the
      motivational properties of alcohol in selectively bred Sardinian alcohol
      preferring (sP) rats. METHODS AND RESULTS: In Experiment 1, the repeated
      administration of SR147778 (0.3-3 mg/kg twice daily, i.p.) specifically
      suppressed the acquisition of alcohol drinking behaviour in alcohol-naive rats
      exposed to the two-bottle "alcohol vs water" choice regimen for 24 h/day. In
      Experiment 2, an acute administration of SR147778 (2.5-10 mg/kg, i.p.)
      specifically reduced alcohol intake in alcohol-experienced rats that were given
      alcohol and water under the two-bottle choice regimen in daily sessions of 4 h.
      In Experiment 3, an acute administration of SR147778 (0.3-3 mg/kg, i.p.)
      suppressed the "alcohol deprivation effect", i.e. the extra-intake of alcohol
      occurring after a period of alcohol abstinence. In Experiment 4, an acute
      administration of SR147778 (0.3-3 mg/kg, i.p.) specifically suppressed the
      extinction responding for alcohol, i.e. the maximal number of lever responses
      reached in the absence of alcohol in rats trained to lever-press for alcohol
      (measure of the motivational properties of alcohol). In Experiment 5, the
      combination of 3 mg/kg of SR147778 (i.p.) and 0.5 g/kg of alcohol (i.p.), a dose
      comparable with those usually consumed by sP rats in each drinking binge, failed
      to induce any conditioned taste aversion. CONCLUSION: Taken together, these
      results extend to SR147778 the anti-alcohol profile of the prototype cannabinoid
      CB(1) receptor antagonist, rimonabant (SR141716), and strengthen the hypothesis
      that the cannabinoid CB(1) receptor is part of the neural substrate mediating
      alcohol intake and the motivational properties of alcohol.

PMID- 15582989
TI  - Vacuolar ATPase regulates zymogen activation in pancreatic acini.
AB  - Supramaximal concentrations of cholecystokinin or its analogue caerulein have
      been shown to stimulate the proteolytic activation of zymogens within the
      pancreatic acinar cell and initiate acute pancreatitis. Previous studies suggest
      that a low pH compartment might be required for activation. To test this
      hypothesis, the effects of agents that modulate intracellular pH on caerulein
      induced trypsin and chymotrypsin activation were studied. Pretreatment of
      pancreatic acini with the proto-ionophore monensin (10 microM) and the weak base
      chloroquine (40 microM) inhibited activation. Pre-incubation with the vacuolar
      ATPase (V-ATPase) inhibitors bafilomycin A(1) and concanamycin A also decreased
      activation in a concentration-dependent manner with 50% inhibition at
      approximately 50 and 25 nM, respectively. Caerulein stimulation caused a time-
      and concentration-dependent translocation of soluble V-ATPase V(1) subunits to a
      membrane fraction, a marker of V-ATPase activation. Carbachol also stimulated
      translocation at supramaximal concentrations. Elevation of cytosolic Ca(2+) by
      thapsigargin was sufficient to induce translocation. Thus, stimulation of V
      ATPase activity appears to be required for agonist-induced zymogen activation in
      the pancreatic acinar cell.

PMID- 15582990
TI  - Thrombomodulin changes the molecular surface of interaction and the rate of
      complex formation between thrombin and protein C.
AB  - The interaction of thrombin with protein C triggers a key down-regulatory process
      of the coagulation cascade. Using a panel of 77 Ala mutants, we have mapped the
      epitope of thrombin recognizing protein C in the absence or presence of the
      cofactor thrombomodulin. Residues around the Na(+) site (Thr-172, Lys-224, Tyr
      225, and Gly-226), the aryl binding site (Tyr-60a), the primary specificity
      pocket (Asp-189), and the oxyanion hole (Gly-193) hold most of the favorable
      contributions to protein C recognition by thrombin, whereas a patch of residues
      in the 30-loop (Arg-35 and Pro-37) and 60-loop (Phe-60h) regions produces
      unfavorable contributions to binding. The shape of the epitope changes
      drastically in the presence of thrombomodulin. The unfavorable contributions to
      binding disappear and the number of residues promoting the thrombin-protein C
      interaction is reduced to Tyr-60a and Asp-189. Kinetic studies of protein C
      activation as a function of temperature reveal that thrombomodulin increases
      >1,000-fold the rate of diffusion of protein C into the thrombin active site and
      lowers the activation barrier for this process by 4 kcal/mol. We propose that the
      mechanism of thrombomodulin action is to kinetically facilitate the productive
      encounter of thrombin and protein C and to allosterically change the conformation
      of the activation peptide of protein C for optimal presentation to the thrombin
      active site.

PMID- 15582991
TI  - Glycosaminoglycans modulate activation, activity, and stability of tripeptidyl
      peptidase I in vitro and in vivo.
AB  - Tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal exopeptidase that
      sequentially removes tripeptides from the N termini of polypeptides and shows a
      minor endoprotease activity. Mutations in TPP I lead to classic late-infantile
      neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease.
      TPP I proenzyme is converted in lysosomes into a mature enzyme with the
      assistance of another protease and is able to autoactivate in acidic pH in vitro
      via a unimolecular mechanism. Because autoactivation in vitro at the pH values
      reported for lysosomes generated inactive enzyme, we intended to determine
      whether physiologically relevant factors can modify this process to also make it
      plausible in vivo. Here, we report that high ionic strength and
      glycosaminoglycans (GAGs) increase yields (ionic strength) or yields and rates
      (GAGs) of activation, enhance degradation of liberated TPP I prosegment
      fragments, and switch effective autoactivation of TPP I proenzyme toward less
      acidic pH values (up to pH 6.0). Although ionic strength and GAGs also inhibited
      TPP I activity in vitro and in living cells, the degree of inhibition (from 20 to
      60%) appears to be of rather limited functional significance. Importantly,
      binding to GAGs improved thermal stability of TPP I and protected the enzyme
      against alkaline pH-induced denaturation in vitro (t((1/2)) of mature enzyme at
      pH 7.4 increased by approximately 8-fold in the presence of heparin) and in vivo
      ( approximately 2-fold higher loss of TPP I in cells deficient in GAGs than in
      control cells after bafilomycin A1 treatment). These findings elucidate a potent
      physiologically relevant mechanism of TPP I regulation by GAGs and suggest that
      generation of the active enzyme via autoactivation can be accomplished not only
      in vitro but in vivo as well.

PMID- 15582992
TI  - Involvement of a flavosemiquinone in the enzymatic oxidation of nitroalkanes
      catalyzed by 2-nitropropane dioxygenase.
AB  - 2-Nitropropane dioxygenase (EC 1.13.11.32) catalyzes the oxidation of
      nitroalkanes into their corresponding carbonyl compounds and nitrite. In this
      study, the ncd-2 gene encoding for the enzyme in Neurospora crassa was cloned,
      expressed in Escherichia coli, and the resulting enzyme was purified. Size
      exclusion chromatography, heat denaturation, and mass spectroscopic analyses
      showed that 2-nitropropane dioxygenase is a homodimer of 80 kDa, containing a
      mole of non-covalently bound FMN per mole of subunit, and is devoid of iron. With
      neutral nitroalkanes and anionic nitronates other than propyl-1- and propyl-2
      nitronate, for which a non-enzymatic free radical reaction involving superoxide
      was established using superoxide dismutase, substrate oxidation occurs within the
      enzyme active site. The enzyme was more specific for nitronates than
      nitroalkanes, as suggested by the second order rate constant k(cat)/K(m)
      determined with 2-nitropropane and primary nitroalkanes with alkyl chain lengths
      between 2 and 6 carbons. The steady state kinetic mechanism with 2-nitropropane,
      nitroethane, nitrobutane, and nitrohexane, in either the neutral or anionic form,
      was determined to be sequential, consistent with oxygen reacting with a reduced
      form of enzyme before release of the carbonyl product. Enzyme-monitored turnover
      with ethyl nitronate as substrate indicated that the catalytically relevant
      reduced form of enzyme is an anionic flavin semiquinone, whose formation requires
      the substrate, but not molecular oxygen, as suggested by anaerobic substrate
      reduction with nitroethane or ethyl nitronate. Substrate deuterium kinetic
      isotope effects with 1,2-[(2)H(4)]nitroethane and 1,1,2-[(2)H(3) ethyl nitronate
      at pH 8 yielded normal and inverse effects on the k(cat)/K(m) value,
      respectively, and were negligible on the k(cat) value. The k(cat)/K(m) and k(cat)
      pH profiles with anionic nitronates showed the requirement of an acid, whereas
      those for neutral nitroalkanes were consistent with the involvement of both an
      acid and a base in catalysis. The kinetic data reported herein are consistent
      with an oxidasestyle catalytic mechanism for 2-nitropropane dioxygenase, in which
      the flavin-mediated oxidation of the anionic nitronates or neutral nitroalkanes
      and the subsequent oxidation of the enzyme-bound flavin occur in two independent
      steps.

PMID- 15582993
TI  - Voltage-dependent changes of TRPV6-mediated Ca2+ currents.
AB  - The physiological role and activation mechanism for most proteins of the
      transient receptor potential (TRP) family are unknown. This is also the case for
      the highly Ca(2+) selective transient receptor potential vanilloid type 6 (TRPV6)
      channel. Patch clamp experiments were performed on transiently transfected human
      embryonic kidney (HEK) cells to address this issue. Currents were recorded under
      various conditions of intracellular Ca(2+) buffering and monitored at the same
      voltage throughout. No TRPV6-mediated Ca(2+) entry was detected under in vivo
      Ca(2+) buffering conditions at a slightly negative holding potential; however,
      moderate depolarization resulted in current activation. Very similar results were
      obtained with different Ca(2+) chelators, either EGTA or BAPTA dialyzing the
      cell. TRPV6 channel activity showed a negative correlation with the intracellular
      free Ca(2+) concentration ([Ca(2+)](i)) and was modulated by the membrane
      potential: Hyperpolarization decreases and depolarization increases TRPV6
      mediated currents. Monovalent ions permeated TRPV6 channels in the absence of
      extracellular divalent cations. These currents were resistant to changes in the
      holding potential while the negative correlation to the [Ca(2+)](i) was
      conserved, indicating that the voltage-dependent current changes depend on
      blocking and unblocking the charge carrier Ca(2+) within the pore. In summary,
      these results suggest that the voltage dependence of TRPV6-mediated Ca(2+) influx
      is of physiological importance since it occurs at cytosolic Ca(2+) buffering and
      takes place within a physiologically relevant membrane potential range.

PMID- 15582994
TI  - Calcium/calmodulin-dependent protein kinase II (CaMKII) localization acts in
      concert with substrate targeting to create spatial restriction for
      phosphorylation.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) acts in diverse cell types
      by phosphorylating proteins with key calcium-dependent functions such as synaptic
      plasticity, electrical excitability, and neurotransmitter synthesis. CaMKII
      displays calcium-dependent binding to proteins in vitro and translocation to
      synaptic sites after glutamatergic activity in neurons. We therefore hypothesized
      that subcellular targeting of CaMKII can direct its substrate specificity in an
      activity-dependent fashion. Here, we examined whether activity-dependent
      colocalization of CaMKII and its substrates could result in regulation of
      substrate phosphorylation in cells. We find that substrates localized at cellular
      membranes required CaMKII translocation to these compartments to achieve
      effective phosphorylation. Spatial barriers to phosphorylation could be overcome
      by translocation and anchoring to the substrate itself or to nearby target
      proteins within the membrane compartment. In contrast, phosphorylation of a
      cytoplasmic counterpart of the substrate does not require CaMKII translocation or
      stable protein-protein binding. Cytosolic phosphorylation is more permissive,
      exhibiting partial calcium-independence. Localization-dependent substrate
      specificity can also show more graded levels of regulation within signaling
      microdomains. We find that colocalization of translocated CaMKII and its
      substrate to lipid rafts in the plasma membrane can modulate the magnitude of
      phosphorylation. Thus, dynamic regulation of both substrate and kinase
      localization provides a powerful and nuanced way to regulate CaMKII signal
      specificity.

PMID- 15582995
TI  - Des-gamma-carboxy prothrombin is a potential autologous growth factor for
      hepatocellular carcinoma.
AB  - Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for
      hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has
      a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of
      Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with
      cell surface receptor Met causing Met autophosphorylation and also to activate
      STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis
      showed that DCP induced STAT3-related transcription. Small interfering RNAs
      against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not
      affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or
      phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that
      DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1
      STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell
      proliferation.

PMID- 15582996
TI  - Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl-
      channel activity.
AB  - Compounds that enhance either the function or biosynthetic processing of the
      cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel may be
      of value in developing new treatments for cystic fibrosis (CF). Previous studies
      suggested that the herbal extract curcumin might affect the processing of a
      common CF mutant, CFTR-DeltaF508. Here, we tested the hypothesis that curcumin
      influences channel function. Curcumin increased CFTR channel activity in excised,
      inside-out membrane patches by reducing channel closed time and prolonging the
      time channels remained open. Stimulation was dose-dependent, reversible, and
      greater than that observed with genistein, another compound that stimulates CFTR.
      Curcumin-dependent stimulation required phosphorylated channels and the presence
      of ATP. We found that curcumin increased the activity of both wild-type and
      DeltaF508 channels. Adding curcumin also increased Cl(-) transport in
      differentiated non-CF airway epithelia but not in CF epithelia. These results
      suggest that curcumin may directly stimulate CFTR Cl(-) channels.

PMID- 15582997
TI  - Multiple signals are required for alpha2,6-sialyltransferase (ST6Gal I)
      oligomerization and Golgi localization.
AB  - A single amino acid difference in the catalytic domain of two isoforms of the
      alpha2,6-sialyltransferase (ST6Gal I) leads to differences in their trafficking,
      processing, and oligomerization. The STtyr isoform is transiently localized in
      the Golgi and is ultimately cleaved and secreted, whereas the STcys isoform is
      stably localized in the Golgi and is not cleaved and secreted. The stable
      localization of STcys is correlated with its enhanced ability to oligomerize. To
      test the hypothesis that multiple signals can mediate Golgi localization and
      further evaluate the role of oligomerization in the localization process, we
      evaluated the effects of individually and simultaneously altering the cytosolic
      tail and transmembrane region of the STcys isoform. We found that the
      localization, processing, and oligomerization of STcys were not substantially
      changed when either the core amino acids of the cytosolic tail were deleted or
      the sequence and length of the transmembrane region were altered. In contrast,
      when these changes were made simultaneously, the STcys isoform was converted into
      a form that was processed, secreted, and weakly oligomerized like STtyr. We
      propose that STcys oligomerization is a secondary event resulting from its
      concentration in the Golgi via mechanisms independently mediated by its cytosolic
      tail and transmembrane region.

PMID- 15582998
TI  - p14ARF induces G2 cell cycle arrest in p53- and p21-deficient cells by down
      regulating p34cdc2 kinase activity.
AB  - The human INK4a gene locus encodes two structurally unrelated tumor suppressor
      proteins, p16(INK4a) and p14(ARF). Although primarily proposed to require a
      functional p53.Mdm-2 signaling axis, recently p14(ARF) has been implicated in p53
      independent cell cycle regulation. Here we show that p14(ARF) preferentially
      induces a G(2) arrest in tumor cells lacking functional p53 and/or p21.
      Expression of p14(ARF) impaired mitotic entry and enforced a primarily
      cytoplasmic localization of p34(cdc2) that was associated with a decrease in
      p34(cdc2) kinase activity and reduced p34(cdc2) protein expression. A direct
      physical interaction between p14(ARF) and p34(cdc2) was, nevertheless, ruled out
      by lack of co-immunoprecipitation. The p14(ARF)-induced depletion of p34(cdc2)
      was associated with impaired cdc25C phosphatase expression and a prominent shift
      to inhibitory Tyr-15-phosphorylation in G(2)-arrested cells lacking either p53,
      p21, or both. Finally, reconstitution of p34(cdc2) using a constitutively active,
      phosphorylation-deficient p34(cdc2AF) mutant alleviated this p14(ARF)-induced
      G(2) arrest, thereby allowing cell cycle progression. Taken together, these data
      indicate that p14(ARF) arrests cells lacking functional p53/p21 in the G(2) phase
      of the cell cycle by targeting p34(cdc2) kinase. This may represent an important
      fail-safe mechanism by which p14(ARF) protects p53/p21-deficient cells from
      unrestrained proliferation.

PMID- 15582999
TI  - A cis-spreading nucleoprotein filament is responsible for the gene silencing
      activity found in the promoter relay mechanism.
AB  - Transcription-generated DNA supercoiling plays a decisive role in a promoter
      relay mechanism for the coordinated expression of genes in the Salmonella
      typhimurium ilvIH-leuO-leuABCD gene cluster. A similar mechanism also operates to
      control expression of the genes in the Escherichia coli ilvIH-leuO-leuABCD gene
      cluster. However, the mechanism underlying the DNA supercoiling effect remained
      elusive. A bacterial gene silencer AT8 was found to be important for the
      repression state of the leuO gene as part of the promoter relay mechanism. In
      this communication, we demonstrated that the gene silencer AT8 is a nucleation
      site for recruiting histone-like nucleoid structuring protein to form a cis
      spreading nucleoprotein filament that is responsible for silencing of the leuO
      gene. With a DNA geometric similarity rather than a DNA sequence specificity, the
      E. coli gene silencer EAT6 was capable of replacing the histone-like nucleoid
      structuring protein nucleation function of the S. typhimurium gene silencer AT8
      for the leuO gene silencing. The interchangeability between DNA geometrical
      elements for supporting the silencing activity in the region is consistent with a
      previous finding that a neighboring transcription activity determines the outcome
      of the gene silencing activity. The geometric requirement, which was revealed for
      this silencing activity, explains the decisive role of transcription-generated
      DNA supercoiling found in the promoter relay mechanism.

PMID- 15583000
TI  - Two-step mechanism of binding of apolipoprotein E to heparin: implications for
      the kinetics of apolipoprotein E-heparan sulfate proteoglycan complex formation
      on cell surfaces.
AB  - The interaction of apolipoprotein E (apoE) with cell-surface heparan sulfate
      proteoglycans is an important step in the uptake of lipoprotein remnants by the
      liver. ApoE interacts predominantly with heparin through the N-terminal binding
      site spanning the residues around 136-150. In this work, surface plasmon
      resonance analysis was employed to investigate how amphipathic alpha-helix
      properties and basic residue organization in this region modulate binding of apoE
      to heparin. The apoE/heparin interaction involves a two-step process; apoE
      initially binds to heparin with fast association and dissociation rates, followed
      by a step exhibiting much slower kinetics. Circular dichroism and surface plasmon
      resonance experiments using a disulfide-linked mutant, in which opening of the N
      terminal helix bundle was prevented, demonstrated that there is no major
      secondary or tertiary structural change in apoE upon heparin binding. Mutations
      of Lys-146, a key residue for the heparin interaction, greatly reduced the
      favorable free energy of binding of the first step without affecting the second
      step, suggesting that electrostatic interaction is involved in the first binding
      step. Although lipid-free apoE2 tended to bind less than apoE3 and apoE4, there
      were no significant differences in rate and equilibrium constants of binding
      among the apoE isoforms in the lipidated state. Discoidal apoE3-phospholipid
      complexes using a substitution mutant (K143R/K146R) showed similar binding
      affinity to wild type apoE3, indicating that basic residue specificity is not
      required for the effective binding of apoE to heparin, unlike its binding to the
      low density lipoprotein receptor. In addition, disruption of the alpha-helix
      structure in the apoE heparin binding region led to an increased favorable free
      energy of binding in the second step, suggesting that hydrophobic interactions
      contribute to the second binding step. Based on these results, it seems that cell
      surface heparan sulfate proteoglycan localizes apoE-enriched remnant lipoproteins
      to the vicinity of receptors by fast association and dissociation.

PMID- 15583001
TI  - Ligand binding is a critical requirement for plasma membrane expression of
      heteromeric kainate receptors.
AB  - Intracellular trafficking of ionotropic glutamate receptors is controlled by
      multiple discrete determinants in receptor subunits. Most such determinants have
      been localized to the cytoplasmic carboxyl-terminal domain, but other domains in
      the subunit proteins can play roles in modulating receptor surface expression.
      Here we demonstrate that formation of an intact glutamate binding site also acts
      as an additional quality-control check for surface expression of homomeric and
      heteromeric kainate receptors. A key ligand-binding residue in the KA2 subunit,
      threonine 675, was mutated to either alanine or glutamate, which eliminated
      affinity for the receptor ligands kainate and glutamate. We found that plasma
      membrane expression of heteromeric GluR6/KA2(T675A) or GluR6/KA2(T675E) kainate
      receptors was markedly reduced compared with wild-type GluR6/KA2 receptors in
      transfected HEK 293 and COS-7 cells and in cultured neurons. Surface expression
      of homomeric KA2 receptors lacking a retention/retrieval determinant (KA2-R/A)
      was also reduced upon mutation of Thr-675 and elimination of the ligand binding
      site. KA2 Thr-675 mutant subunits were able to co-assemble with GluR5 and GluR6
      subunits and were degraded at the same rate as wild-type KA2 subunit protein.
      These results suggest that glutamate binding and associated conformational
      changes are prerequisites for forward trafficking of intracellular kainate
      receptors following multimeric assembly.

PMID- 15583002
TI  - Spatio-temporal dynamics of protein kinase B/Akt signaling revealed by a
      genetically encoded fluorescent reporter.
AB  - The serine/threonine kinase protein kinase B (PKB)/Akt is a critical regulator of
      insulin signaling, cell survival, and oncogenesis. The activation mechanisms of
      this key kinase are well characterized. In contrast, inactivation of PKB
      signaling by phosphatases is less well understood. To study the dynamics of PKB
      signaling in live cells, we generated a genetically encoded fluorescent reporter
      for PKB activity that reversibly responds to stimuli activating
      phosphatidylinositol 3-kinase. Specifically, phosphorylation of the reporter
      expressed in mammalian cells causes changes in fluorescence resonance energy
      transfer, allowing real-time imaging of phosphorylation catalyzed by PKB. Because
      of its reversibility, the reporter also allows termination of PKB signaling by
      phosphatases to be monitored. We found that PKB signaling in the cytosol was more
      rapid and more transient compared with that in the nucleus, suggesting the
      presence of differentially regulated phosphatase activity in these two
      compartments. Furthermore, targeting of the reporter to the plasma membrane,
      where PKB is activated, resulted in accelerated and prolonged response compared
      with the response in the cytosol, suggesting that release of PKB or its
      substrates from the membrane is required for desensitization of PKB signaling.
      These data reveal spatio-temporal gradients of both signal propagation and signal
      termination in PKB signaling.

PMID- 15583003
TI  - autoregulatory role of endothelium-derived nitric oxide (NO) on
      Lipopolysaccharide-induced vascular inducible NO synthase expression and
      function.
AB  - Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is
      responsible for sepsis-induced hypotension and plays a major contributory role in
      the ensuing multiorgan failure. The present study aimed to elucidate the role of
      endothelial NO in lipopolysaccharide (LPS)-induced iNOS expression, in isolated
      rat aortic rings. Exposure to LPS (1 mug/ml, 5 h) resulted in a reversal of
      phenylephrine precontracted tone in aortic rings (70.7 +/- 3.2%). This relaxation
      was associated with iNOS expression and NF-kappaB activation. Positive
      immunoreactivity for iNOS protein was localized in medial and adventitial layers
      of LPS-treated aortic rings. Removal of the endothelium rendered aortic rings
      resistant to LPS-induced relaxation (8.9 +/- 4.5%). Western blotting of these
      rings demonstrated an absence of iNOS expression. However, treatment of
      endothelium-denuded rings with the NO donor, diethylamine-NONOate (0.1 mum),
      restored LPS-induced relaxation (61.6 +/- 6.6%) and iNOS expression to levels
      comparable with arteries with intact endothelium. Blockade of endothelial NOS
      (eNOS) activation using geldanamycin and radicicol, inhibitors of heat shock
      protein 90, in endothelium-intact arteries suppressed both LPS-induced relaxation
      and LPS-induced iNOS expression (9.0 +/- 8.0% and 2.0 +/- 6.2%, respectively).
      Moreover, LPS treatment (12.5 mg/kg, intravenous, 15 h) of wild-type mice
      resulted in profound elevation of plasma [NO(x)] measurements that were reduced
      by approximately 50% in eNOS knock-out animals. Furthermore, LPS-induced changes
      in vascular reactivity and iNOS expression evident in wild-type tissues were
      profoundly suppressed in tissues taken from eNOS knockout animals. Together,
      these data suggest that eNOS-derived NO, in part via activation of NF-kappaB,
      regulates iNOS-induction by LPS. This study provides the first demonstration of a
      proinflammatory role of vascular eNOS in sepsis.

PMID- 15583004
TI  - Sites on calmodulin that interact with the C-terminal tail of Cav1.2 channel.
AB  - Two fragments of the C-terminal tail of the alpha(1) subunit (CT1, amino acids
      1538-1692 and CT2, amino acids 1596-1692) of human cardiac L-type calcium channel
      (Ca(V)1.2) have been expressed, refolded, and purified. A single Ca(2+)
      calmodulin binds to each fragment, and this interaction with Ca(2+)-calmodulin is
      required for proper folding of the fragment. Ca(2+)-calmodulin, bound to these
      fragments, is in a more extended conformation than calmodulin bound to a
      synthetic peptide representing the IQ motif, suggesting that either the
      conformation of the IQ sequence is different in the context of the longer
      fragment, or other sequences within CT2 contribute to the binding of calmodulin.
      NMR amide chemical shift perturbation mapping shows the backbone conformation of
      calmodulin is nearly identical when bound to CT1 and CT2, suggesting that amino
      acids 1538-1595 do not contribute to or alter calmodulin binding to amino acids
      1596-1692 of Ca(V)1.2. The interaction with CT2 produces the greatest changes in
      the backbone amides of hydrophobic residues in the N-lobe and hydrophilic
      residues in the C-lobe of calmodulin and has a greater effect on residues located
      in Ca(2+) binding loops I and II in the N-lobe relative to loops III and IV in
      the C-lobe. In conclusion, Ca(2+)-calmodulin assumes a novel conformation when
      part of a complex with the C-terminal tail of the Ca(V)1.2 alpha(1) subunit that
      is not duplicated by synthetic peptides corresponding to the putative binding
      motifs.

PMID- 15583005
TI  - Tandemly duplicated acyl carrier proteins, which increase polyketide antibiotic
      production, can apparently function either in parallel or in series.
AB  - Polyketide biosynthesis involves the addition of subunits commonly derived from
      malonate or methylmalonate to a starter unit such as acetate. Type I polyketide
      synthases are multifunctional polypeptides that contain one or more modules, each
      of which normally contains all the enzymatic domains for a single round of
      extension and modification of the polyketide backbone. Acyl carrier proteins
      (ACP(s)) hold the extender unit to which the starter or growing chain is added.
      Normally there is one ACP for each ketosynthase module. However, there are an
      increasing number of known examples of tandemly repeated ACP domains, whose
      function is as yet unknown. For the doublet and triplet ACP domains in the
      biosynthetic pathway for the antibiotic mupirocin from Pseudomonas fluorescens
      NCIMB10586 we have inactivated ACP domains by inframe deletion and amino acid
      substitution of the active site serine. By deletion analysis each individual ACP
      from a cluster can provide a basic but reduced activity for the pathway. In the
      doublet cluster, substitution analysis indicates that the pathway may follow two
      parallel routes, one via each of the ACPs, thus increasing overall pathway flow.
      In the triplet cluster, substitution in ACP5 blocked the pathway. Thus ACP5
      appears to be arranged "in series" to ACP6 and ACP7. Thus although both the
      doublet and triplet clusters increase antibiotic production, the mechanisms by
      which they do this appear to be different and depend specifically on the
      biosynthetic stage involved. The function of some ACPs may be determined by their
      location in the protein rather than absolute enzymic activity.

PMID- 15583006
TI  - Functional interaction of protein kinase Calpha with the tyrosine kinases Syk and
      Src in human platelets.
AB  - There is a high degree of cross-talk between tyrosine phosphorylation and the
      serine/threonine phosphorylation signaling pathways. Here we show a physical and
      functional interaction between the classical protein kinase C isoform (cPKC),
      PKCalpha, and two major nonreceptor tyrosine kinases in platelets, Syk and Src.
      In the presence of the cPKC-selective inhibitor Go6976, platelet 5
      hydroxytryptamine release was abolished in response to co-activation of
      glycoproteins VI and Ib-IX-V by the snake venom alboaggregin A, whereas platelet
      aggregation was substantially inhibited. Of the two platelet cPKCs, PKCalpha but
      not PKCbeta was activated, occurring in an Syk- and phospholipase C-dependent
      manner. Syk and PKCalpha associate in a stimulation-dependent manner, requiring
      Syk but not PKC activity. PKCalpha and Syk also co-translocate from the cytosol
      to the plasma membrane upon platelet activation, in a manner dependent upon the
      activities of both kinases. Although PKCalpha is phosphorylated on tyrosine
      downstream of Syk, we provide evidence against phosphorylation of Syk by
      PKCalpha, consistent with a lack of effect of PKCalpha inhibition on Syk
      activity. PKCalpha also associates with Src; although in contrast to interaction
      with Syk, PKCalpha activity is required for the association of these kinases but
      not the stimulation-induced translocation of Src to the cell membrane. Finally,
      the activity of Src is negatively regulated by PKC, as shown by potentiation of
      Src activity in the presence of the PKC inhibitors GF109203X or Go6976.
      Therefore, there is a complex interplay between PKCalpha, Syk, and Src involving
      physical interaction, phosphorylation, translocation within the cell, and
      functional activity regulation.

PMID- 15583007
TI  - HNF-4-dependent induction of apolipoprotein A-IV gene transcription by an apical
      supply of lipid micelles in intestinal cells.
AB  - Apolipoprotein (apo) A-IV, a component of triglyceride-rich lipoproteins secreted
      by the small intestine, has been shown to play an important role in the control
      of lipid homeostasis. Numerous studies have described the induction of apoA-IV
      gene expression by lipids, but the molecular mechanisms involved in this process
      remain unknown. In this study, we have demonstrated that a lipid bolus induced
      transcription of the apoA-IV gene in transgenic mice and that the regulatory
      region of the apoA-IV gene, composed of the apoC-III enhancer and the apoA-IV
      promoter (eC3-A4), was responsible for this induction. In enterocyte Caco-2/TC7
      cells, a permanent supply of lipids at the basal pole induced expression of the
      apoA-IV gene both at the transcriptional level and through mRNA stabilization.
      ApoA-IV gene transcription and protein secretion were further induced by an
      apical supply of complex lipid micelles mimicking the composition of duodenal
      micelles, and this effect was not reproduced by apical delivery of different
      combinations of micelle components. Only induction of the apoA-IV gene by lipid
      micelles involved the participation of hepatic nuclear factor (HNF)-4, as
      demonstrated using a dominant negative form of this transcription factor.
      Accordingly, lipid micelles increased the DNA binding activity of HNF-4 on the
      eC3-A4 region. These results emphasize the importance of physiological delivery
      of dietary lipids on apoA-IV gene expression and the implication of HNF-4 in this
      regulation.

PMID- 15583008
TI  - Residues contributing to the Ca2+ and K+ binding pocket of the NCKX2 Na+/Ca2+-K+
      exchanger.
AB  - The Na(+)/Ca(2+)-K(+) exchanger (NCKX) extrudes Ca(2+) from cells utilizing both
      the inward Na(+) gradient and the outward K(+) gradient. NCKX is thought to
      operate by a consecutive mechanism in which a cation binding pocket accommodates
      both Ca(2+) and K(+) and alternates between inward and outward facing
      conformations. Here we developed a simple fluorometric method to analyze changes
      in K(+) and Ca(2+) dependences of mutant NCKX2 proteins in which candidate
      residues within membrane-spanning domains were substituted. The largest shifts in
      both K(+) and Ca(2+) dependences compared with wild-type NCKX2 were observed for
      the charge-conservative substitutions of Glu(188) and Asp(548), whereas the size
      conservative substitutions resulted in nonfunctional proteins. Substitution of
      several other residues including two proline residues (Pro(187) and Pro(547)),
      three additional acidic residues (Asp(258), Glu(265), Glu(533)), and two hydroxyl
      containing residues (Ser(185) and Ser(545)) showed smaller shifts, but shifts in
      Ca(2+) dependence were invariably accompanied by shifts in K(+) dependence. We
      conclude that Glu(188) and Asp(548) are the central residues of a single cation
      binding pocket that can accommodate both K(+) and Ca(2+). Furthermore, a single
      set of residues lines a transport pathway for both K(+) and Ca(2+).

PMID- 15583009
TI  - Alteration of lithium pharmacology through manipulation of phosphoadenosine
      phosphate metabolism.
AB  - Bisphosphate 3'-nucleotidase (BPNT1 in mammals and Met22/Hal2 in yeast) is one of
      five members of a family of signaling phosphatases united through a common
      tertiary structure and inhibition by subtherapeutic doses of the antibipolar drug
      lithium. Here we report a role for 3'-nucleotidase and its substrate, 3'
      phosphoadenosine 5'-phosphate (PAP), in mediating the cellular effects of
      lithium. Lithium-induced inhibition of growth in yeast cells may be overcome by
      dose-dependent heterologous expression of human BPNT1. Disruption of the yeast 3'
      nucleotidase gene or treatment of cells with lithium results in a >80-fold
      accumulation of PAP and leads to potent growth inhibition. These data indicate
      that the accumulation of a 3'-nucleotidase substrate, such as PAP, mediates the
      toxicity of lithium. To further probe this model we examined the growth
      inhibitory effects of lithium under conditions in which PAP biosynthetic
      machinery was concomitantly down-regulated. Disruption of met3 or met14 genes
      (ATP sulfurylase or phosphosulfate kinase), transcriptional down-regulation of
      MET3 through methionine addition, or administration of chlorate, a widely used
      cell-permeable sulfurylase inhibitor, function to reduce lithium-induced
      intracellular PAP accumulation and lithium toxicity; all of these effects were
      reversed by heterologous expression of human sulfurylase and kinase.
      Collectively, our data support a role for 3'-nucleotidase activity and PAP
      metabolism in aspects of lithium's mechanism of action and provide a platform for
      development of novel pharmacological modulators aimed at improving therapies for
      the treatment of bipolar disorder.

PMID- 15583010
TI  - Cluster formation of inositol 1,4,5-trisphosphate receptor requires its
      transition to open state.
AB  - The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) Ca(2+) channel plays
      pivotal roles in many aspects of physiological and pathological events. It was
      previously reported that IP(3)R forms clusters on the endoplasmic reticulum when
      cytosolic Ca(2+) concentration ([Ca(2+)](C)) is elevated. However, the molecular
      mechanism of IP(3)R clustering remains largely unknown, and thus its
      physiological significance is far from clear. In this study we found that the
      time course of clustering of green fluorescent protein-tagged IP(3)R type 1 (GFP
      IP(3)R1), evoked by IP(3)-generating agonists, did not correlate with [Ca(2+)](C)
      but seemed compatible with cytoplasmic IP(3) concentration. IP(3) production
      alone induced GFP-IP(3)R1 clustering in the absence of a significant increase in
      [Ca(2+)](C) but elevated [Ca(2+)](C) without IP(3) production did not. Moreover
      IP(3)R1 mutants that do not undergo an IP(3)-induced conformational change failed
      to form clusters. Thus, IP(3)R clustering is induced by its IP(3)-induced
      conformational change to the open state. We also found that GFP-IP(3)R1 clusters
      colocalized with ERp44, a luminal protein of endoplasmic reticulum that inhibits
      its channel activity. This is the first example of ligand-induced clustering of a
      ligand-gated channel protein.

PMID- 15583011
TI  - Apoptotic cells with oxidation-specific epitopes are immunogenic and
      proinflammatory.
AB  - Oxidation of low density lipoprotein (LDL) generates a variety of oxidatively
      modified lipids and lipid-protein adducts that are immunogenic and
      proinflammatory, which in turn contribute to atherogenesis. Cells undergoing
      apoptosis also display oxidized moieties on their surface membranes, as
      determined by binding of oxidation-specific monoclonal antibodies. In the present
      paper, we demonstrated by mass spectrometry that in comparison with viable cells,
      membranes of cells undergoing apoptosis contain increased levels of biologically
      active oxidized phospholipids (OxPLs). Indeed, immunization of mice with
      syngeneic apoptotic cells induced high autoantibody titers to various oxidation
      specific epitopes of oxidized LDL, including OxPLs containing phosphorylcholine,
      whereas immunization with viable thymocytes, primary necrotic thymocytes, or
      phosphate-buffered saline did not. Reciprocally, these antisera specifically
      bound to apoptotic cells through the recognition of oxidation-specific epitopes.
      Moreover, splenocyte cultures from mice immunized with apoptotic cells
      spontaneously released significant levels of T helper cell (Th) 1 and Th2
      cytokines, whereas splenocytes from controls yielded only low levels. Finally, we
      demonstrated that the OxPLs of apoptotic cells activated endothelial cells to
      induce monocyte adhesion, a proinflammatory response that was abrogated by an
      antibody specific to oxidized phosphatidylcholine. These results suggest that
      apoptotic cell death generates oxidatively modified moieties, which can induce
      autoimmune responses and a local inflammatory response by recruiting monocytes
      via monocyte-endothelial cell interaction.

PMID- 15583012
TI  - SIGN-R1 contributes to protection against lethal pneumococcal infection in mice.
AB  - Rapid clearance of pathogens is essential for successful control of pyogenic
      bacterial infection. Previous experiments have shown that antibody to specific
      intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1 inhibits uptake of
      capsular polysaccharide by marginal zone macrophages, suggesting a role for SIGN
      R1 in this process. We now demonstrate that mice lacking SIGN-R1 (a mouse
      homologue of human dendritic cell-SIGN receptor) are significantly more
      susceptible to Streptococcus pneumoniae infection and fail to clear S. pneumoniae
      from the circulation. Marginal zone and peritoneal macrophages show impaired
      bacterial recognition associated with an inability to bind T-independent type 2
      antigens such as dextran. Our work represents the first evidence for a protective
      in vivo role for a SIGN family molecule.

PMID- 15583013
TI  - Crucial role for ecto-5'-nucleotidase (CD73) in vascular leakage during hypoxia.
AB  - Extracellular adenosine has been widely implicated in adaptive responses to
      hypoxia. The generation of extracellular adenosine involves phosphohydrolysis of
      adenine nucleotide intermediates, and is regulated by the terminal enzymatic step
      catalyzed by ecto-5'-nucleotidase (CD73). Guided by previous work indicating that
      hypoxia-induced vascular leakage is, at least in part, controlled by adenosine,
      we generated mice with a targeted disruption of the third coding exon of Cd73 to
      test the hypothesis that CD73-generated extracellular adenosine functions in an
      innate protective pathway for hypoxia-induced vascular leakage. Cd73(-/-) mice
      bred and gained weight normally, and appeared to have an intact immune system.
      However, vascular leakage was significantly increased in multiple organs, and
      after subjection to normobaric hypoxia (8% O(2)), Cd73(-/-) mice manifested
      fulminant vascular leakage, particularly prevalent in the lung. Histological
      examination of lungs from hypoxic Cd73(-/-) mice revealed perivascular
      interstitial edema associated with inflammatory infiltrates surrounding larger
      pulmonary vessels. Vascular leakage secondary to hypoxia was reversed in part by
      adenosine receptor agonists or reconstitution with soluble 5'-nucleotidase.
      Together, our studies identify CD73 as a critical mediator of vascular leakage in
      vivo.

PMID- 15583014
TI  - CD27 expression promotes long-term survival of functional effector-memory CD8+
      cytotoxic T lymphocytes in HIV-infected patients.
AB  - Human immunodeficiency virus (HIV)-specific CD8(+) T cells persist in high
      frequencies in HIV-infected patients despite impaired CD4(+) T helper response to
      the virus, but, unlike other differentiated effector cytotoxic T lymphocytes,
      most continue to express the tumor necrosis factor receptor family member CD27.
      Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts,
      we examined the nature of expression and potential functional consequences of
      CD27 expression on HIV-specific CD8(+) T cells. Analysis of CD27(+) and CD27(-) T
      cells derived from the same HIV-specific clone revealed that retention of CD27
      did not interfere with acquisition of effector functions, and that after T cell
      receptor stimulation, CD27(+) cells that concurrently were triggered via CD27
      exhibited more resistance to apoptosis, interleukin 2 production, and
      proliferation than CD27(-) T cells. After transfer back into an HIV-infected
      patient, autologous HIV-specific CD27(-) T cells rapidly disappeared, but CD27(+)
      T cells derived from the same clone persisted at high frequency. Our findings
      suggest that the CD27-CD70 interaction in HIV infection may provide CD27(+)
      CD8(+) T cells with a survival advantage and compensate for limiting or absent
      CD4(+) T help to maintain the CD8 response.

PMID- 15583015
TI  - Dynamic repositioning of CD4 and CD8 genes during T cell development.
AB  - Although stable repression of CD4 and CD8 genes is a central feature of T cell
      lineage commitment, we lack detailed information about the timing and mechanism
      of this repression. Stable gene repression has been linked to the position of
      genes within the nucleus. Therefore, information about the nuclear position of
      CD4 and CD8 genes during T cell development could provide insights into both the
      mechanism of regulation of CD4 and CD8 genes, and the process of lineage
      commitment. Here, we report that lineage-specific repression of CD4 and CD8 genes
      is associated with the repositioning of alleles close to heterochromatin. We also
      provide evidence that the relocalization of CD4 and CD8 genes to heterochromatin
      can occur as an early response to positive selection signals. We discuss our
      results in terms of our current knowledge of CD4 and CD8 gene regulation and CD4
      versus CD8 lineage commitment.

PMID- 15583016
TI  - Centromeric repositioning of coreceptor loci predicts their stable silencing and
      the CD4/CD8 lineage choice.
AB  - The differentiation of CD4(+) CD8(+) double positive (DP) thymocytes requires the
      irreversible choice between two alternative lineages, distinguished by the
      mutually exclusive expression of either CD4 or CD8. Differentiating DP cells
      transiently down-regulate both CD4 and CD8, and this has complicated the debate
      whether the mechanism of CD4/CD8 lineage choice is instructive,
      stochastic/selective, or more complex in nature. Using fluorescence in situ
      hybridization, we show that the stable silencing of coreceptor loci, and
      ultimately lineage choice, is predicted by the spatial repositioning of
      coreceptor alleles to centromeric heterochromatin domains. These data provide
      evidence that lineage-specific developmental programs are established early
      during the transition from the DP to the single positive stage.

PMID- 15583017
TI  - T cell cross-reactivity and conformational changes during TCR engagement.
AB  - All thymically selected T cells are inherently cross-reactive, yet many data
      indicate a fine specificity in antigen recognition, which enables virus escape
      from immune control by mutation in infections such as the human immunodeficiency
      virus (HIV). To address this paradox, we analyzed the fine specificity of T cells
      recognizing a human histocompatibility leukocyte antigen (HLA)-A2-restricted,
      strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority of 171 variant
      peptides tested bound HLA-A2, but only one third were recognized. Surprisingly,
      one recognized variant (SLYNTVATL) showed marked differences in structure when
      bound to HLA-A2. T cell receptor (TCR) recognition of variants of these two
      peptides implied that they adopted the same conformation in the TCR-peptide-major
      histocompatibility complex (MHC) complex. However, the on-rate kinetics of TCR
      binding were identical, implying that conformational changes at the TCR-peptide
      MHC binding interface occur after an initial permissive antigen contact. These
      findings have implications for the rational design of vaccines targeting viruses
      with unstable genomes.

PMID- 15583018
TI  - Evidence for selective transformation of autoreactive immature plasma cells in
      mice deficient in Fasl.
AB  - Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia and
      systemic autoimmunity and also greatly increase the risk of B cell neoplasms. B
      lymphomas occurring in Fasl mutant (gld) mice usually are immunoglobulin (Ig)
      isotype switched, secrete Ig, and are plasmacytoid in appearance but lack Myc
      translocations characteristic of other plasma cell (PC) neoplasms. Here, we
      explore the relationship between B cell autoreactivity and transformation and use
      gene expression profiling to further classify gld plasmacytoid lymphomas (PLs)
      and to identify genes of potential importance in transformation. We found that
      the majority of PLs derive from antigen-experienced autoreactive B cells
      producing antinuclear antibody or rheumatoid factor and exhibit the skewed Ig V
      gene repertoire and Ig gene rearrangement patterns associated with these
      specificities. Gene expression profiling revealed that both primary and
      transplanted PLs share a transcriptional profile that places them at an early
      stage in PC differentiation and distinguishes them from other B cell neoplasms.
      In addition, genes were identified whose altered expression might be relevant in
      lymphomagenesis. Our findings provide a strong case for targeted transformation
      of autoreactive B cells in gld mice and establish a valuable model for
      understanding the relationship between systemic autoimmunity and B cell
      neoplasia.

PMID- 15583019
TI  - The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM
      1+ endothelial cells in splenic marginal sinus organization.
AB  - Marginal zones (MZs) are microdomains in the spleen that contain various types of
      immune cells, including MZ B cells, MOMA1(+) metallophilic macrophages, and
      mucosal addressin cell adhesion molecule 1 (MAdCAM-1)(+) endothelial cells.
      MAdCAM-1(+) and MOMA1(+) cells line the sinus, that separates MZs from splenic
      follicles. Here we show that a receptor for the lysophospholipid sphingosine-1
      phosphate (S1P), S1P(3), is required for normal numbers of splenic immature and
      MZ B cells, and for S1P-induced chemotaxis of MZ B cells. S1P(3) is also
      essential for proper alignment of MOMA1(+) macrophages and MAdCAM-1(+)
      endothelial cells along the marginal sinus. The lack of cohesion of the marginal
      sinus in S1P(3)(-/-) mice affects MZ B cell functions, as wild-type (WT) MZ B
      cells migrate more into S1P(3)(-/-) follicles than into WT follicles after
      treatment with lipopolysaccharide. Additionally, short-term homing experiments
      demonstrate that WT MZ B cells home to the S1P(3)(-/-) spleen in increased
      numbers, suggesting a role for the marginal sinus in regulating MZ B cells
      numbers. Moreover, S1P(3)(-/-) mice are defective in mounting immune responses to
      thymus-independent antigen type 2 due to defects in radiation-resistant cells in
      the spleen. These data identify lysophospholipids and the S1P(3) receptor as
      essential regulators of the MZ sinus and its role as a barrier to the follicle.

PMID- 15583020
TI  - The ETS transcription factor Spi-B is required for human plasmacytoid dendritic
      cell development.
AB  - A number of transcription factors that act as molecular switches for
      hematopoietic lineage decisions have been identified. We recently described the
      ETS transcription factor Spi-B to be exclusively expressed in plasmacytoid
      dendritic cells (pDCs), but not in myeloid DCs. To assess whether Spi-B is
      required for pDC development we used an RNA interference knock down approach to
      specifically silence Spi-B protein synthesis in CD34(+) precursor cells. We
      observed that a knock down of Spi-B mRNA strongly inhibited the ability of
      CD34(+) precursor cells to develop into pDCs in both in vitro assays as well as
      in vivo upon injection into recombination activating gene 2(-/-) gamma common(-/
      ) mice. The observed effects were restricted to the pDC lineage as the
      differentiation of pro-B cells and CD14(+) myeloid cells was not inhibited but
      slightly elevated by Spi-B knock down. Knock down of the related ETS factor PU.1
      also inhibited in vitro development of CD34(+) cells into pDCs. However, in
      contrast to Spi-B, PU.1 knock down inhibited B cell and myeloid cell development
      as well. These results identify Spi-B as a key regulator of human pDC
      development.

PMID- 15583021
TI  - Estrogen receptor mutations in human disease.
AB  - As early as the 1800s, the actions of estrogen have been implicated in the
      development and progression of breast cancer. The estrogen receptor (ER) was
      identified in the late 1950s and purified a few years later. However, it was not
      until the 1980s that the first ER was molecularly cloned, and in the mid 1990s, a
      second ER was cloned. These two related receptors are now called ERalpha and
      ERbeta, respectively. Since their discovery, much research has focused on
      identifying alterations within the coding sequence of these receptors in clinical
      samples. As a result, a large number of naturally occurring splice variants of
      both ERalpha and ERbeta have been identified in normal epithelium and diseased or
      cancerous tissues. In contrast, only a few point mutations have been identified
      in human patient samples from a variety of disease states, including breast
      cancer, endometrial cancer, and psychiatric diseases. To elucidate the mechanism
      of action for these variant isoforms or mutant receptors, experimental
      mutagenesis has been used to analyze the function of distinct amino acid residues
      in the ERs. This review will focus on ERalpha and ERbeta alterations in breast
      cancer.

PMID- 15583022
TI  - Peroxisome proliferator-activated receptor-gamma calls for activation in
      moderation: lessons from genetics and pharmacology.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      prototypical member of the nuclear receptor superfamily and integrates the
      control of energy, lipid, and glucose homeostasis. PPARgamma can bind a variety
      of small lipophilic compounds derived from metabolism and nutrition. These
      ligands, in turn, determine cofactor recruitment to PPARgamma, regulating the
      transcription of genes in a variety of metabolic pathways. PPARgamma is the main
      target of the thiazolidinedione class of insulin-sensitizing drugs, which are
      currently a mainstay of therapy for type 2 diabetes. However, this therapy has a
      number of side effects. Here, we review the clinical consequences of PPARgamma
      polymorphisms in humans, as well as several studies in mice using general or
      tissue-specific knockout techniques. We also discuss the recent pharmacological
      literature describing a variety of new PPARgamma partial agonists and
      antagonists, as well as pan-PPAR agonists. The results of these studies have
      added to the understanding of PPARgamma function, allowing us to hypothesize a
      general mechanism of PPARgamma action and speculate on future trends in the use
      of PPARgamma as a target in the treatment of type II diabetes.

PMID- 15583023
TI  - Pancreas transplantation: indications and consequences.
AB  - Pancreas transplantation continues to evolve as a strategy in the management of
      diabetes mellitus. The first combined pancreas-kidney transplant was reported in
      1967, but pancreas transplant now represents a number of procedures, each with
      different indications, risks, benefits, and outcomes. This review will summarize
      these procedures, including their risks and outcomes in comparison to kidney
      transplantation alone, and how or if they affect the consequences of diabetes:
      hyperglycemia, hypoglycemia, and microvascular and macrovascular complications.
      In addition, the new risks introduced by immunosuppression will be reviewed,
      including infections, cancer, osteoporosis, reproductive function, and the impact
      of immunosuppression medications on blood pressure, lipids, and glucose
      tolerance. It is imperative that an endocrinologist remain involved in the care
      of the pancreas transplant recipient, even when glucose is normal, because of the
      myriad of issues encountered post transplant, including ongoing management of
      diabetic complications, prevention of bone loss, and screening for failure of the
      pancreas graft with reinstitution of treatment when indicated. Although long-term
      patient and graft survival have improved greatly after pancreas transplant, a
      multidisciplinary team is needed to maximize long-term quality, as well as
      quantity, of life for the pancreas transplant recipient.

PMID- 15583024
TI  - Overview of steroidogenic enzymes in the pathway from cholesterol to active
      steroid hormones.
AB  - Significant advances have taken place in our knowledge of the enzymes involved in
      steroid hormone biosynthesis since the last comprehensive review in 1988. Major
      developments include the cloning, identification, and characterization of
      multiple isoforms of 3beta-hydroxysteroid dehydrogenase, which play a critical
      role in the biosynthesis of all steroid hormones and 17beta-hydroxysteroid
      dehydrogenase where specific isoforms are essential for the final step in active
      steroid hormone biosynthesis. Advances have taken place in our understanding of
      the unique manner that determines tissue-specific expression of P450aromatase
      through the utilization of alternative promoters. In recent years, evidence has
      been obtained for the expression of steroidogenic enzymes in the nervous system
      and in cardiac tissue, indicating that these tissues may be involved in the
      biosynthesis of steroid hormones acting in an autocrine or paracrine manner. This
      review presents a detailed description of the enzymes involved in the
      biosynthesis of active steroid hormones, with emphasis on the human and mouse
      enzymes and their expression in gonads, adrenal glands, and placenta.

PMID- 15583025
TI  - From hyperglycemia to diabetic kidney disease: the role of metabolic,
      hemodynamic, intracellular factors and growth factors/cytokines.
AB  - At present, diabetic kidney disease affects about 15-25% of type 1 and 30-40% of
      type 2 diabetic patients. Several decades of extensive research has elucidated
      various pathways to be implicated in the development of diabetic kidney disease.
      This review focuses on the metabolic factors beyond blood glucose that are
      involved in the pathogenesis of diabetic kidney disease, i.e., advanced glycation
      end-products and the aldose reductase system. Furthermore, the contribution of
      hemodynamic factors, the renin-angiotensin system, the endothelin system, and the
      nitric oxide system, as well as the prominent role of the intracellular signaling
      molecule protein kinase C are discussed. Finally, the respective roles of TGF
      beta, GH and IGFs, vascular endothelial growth factor, and platelet-derived
      growth factor are covered. The complex interplay between these different pathways
      will be highlighted. A brief introduction to each system and description of its
      expression in the normal kidney is followed by in vitro, experimental, and
      clinical evidence addressing the role of the system in diabetic kidney disease.
      Finally, well-known and potential therapeutic strategies targeting each system
      are discussed, ending with an overall conclusion.

PMID- 15583026
TI  - A lipid boundary separates APP and secretases and limits amyloid beta-peptide
      generation.
AB  - Millions of patients suffer from Alzheimer's disease, and intensive efforts to
      find a cure for this devastating disorder center on the proteases, which release
      the deadly amyloid beta-peptide from its precursor. The cutting procedure is
      thought to be cholesterol dependent and strategies to lower cholesterol as
      therapeutic treatment are under intensive investigation. Recent findings suggest
      that the complete proteolytic machinery required for amyloid beta-peptide
      generation is located within lipid rafts. Data by Dotti and colleagues (Abad
      Rodriguez et al., 2004), in this issue, suggest that rafts isolate the cutting
      machinery away from its deadly substrate. These findings describe a novel
      mechanism for controlling proteolytic activity by building a lipid boundary
      between proteases and their substrates.

PMID- 15583027
TI  - The kinesin Eg5 drives poleward microtubule flux in Xenopus laevis egg extract
      spindles.
AB  - Although mitotic and meiotic spindles maintain a steady-state length during
      metaphase, their antiparallel microtubules slide toward spindle poles at a
      constant rate. This "poleward flux" of microtubules occurs in many organisms and
      may provide part of the force for chromosome segregation. We use quantitative
      image analysis to examine the role of the kinesin Eg5 in poleward flux in
      metaphase Xenopus laevis egg extract spindles. Pharmacological inhibition of Eg5
      results in a dose-responsive slowing of flux, and biochemical depletion of Eg5
      significantly decreases the flux rate. Our results suggest that ensembles of
      nonprocessive Eg5 motors drive flux in metaphase Xenopus extract spindles.

PMID- 15583028
TI  - Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone
      microtubules.
AB  - We identified and characterized a human orthologue of Rif1 protein, which in
      budding yeast interacts in vivo with the major duplex telomeric DNA binding
      protein Rap1p and negatively regulates telomere length. Depletion of hRif1 by RNA
      interference in human cancer cells impaired cell growth but had no detectable
      effect on telomere length, although hRif1 overexpression in S. cerevisiae
      interfered with telomere length control, in a manner specifically dependent on
      the presence of yeast Rif1p. No localization of hRif1 on normal human telomeres,
      or interaction with the human telomeric proteins TRF1, TRF2, or hRap1, was
      detectable. However, hRif1 efficiently translocated to telomerically located DNA
      damage foci in response to the synthesis of aberrant telomeres directed by mutant
      template telomerase RNA. The hRif1 level rose during late S/G2 but hRif1 was not
      visible on chromosomes in metaphase and anaphase; however, notably, specifically
      during early anaphase, hRif1 aligned along a subset of the midzone microtubules
      between the separating chromosomes. In telophase, hRif1 localized to chromosomes,
      and in interphase, it was intranuclear. These results define a novel subcellular
      localization behavior for hRif1 during the cell cycle.

PMID- 15583029
TI  - DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7.
AB  - G2/M checkpoints prevent mitotic entry upon DNA damage or replication inhibition
      by targeting the Cdc2 regulators Cdc25 and Wee1. Although Wee1 protein stability
      is regulated by DNA-responsive checkpoints, the vertebrate pathways controlling
      Wee1 degradation have not been elucidated. In budding yeast, stability of the
      Wee1 homologue, Swe1, is controlled by a regulatory module consisting of the
      proteins Hsl1 and Hsl7 (histone synthetic lethal 1 and 7), which are targeted by
      the morphogenesis checkpoint to prevent Swe1 degradation when budding is
      inhibited. We report here the identification of Xenopus Hsl7 as a positive
      regulator of mitosis that is controlled, instead, by an entirely distinct
      checkpoint, the DNA replication checkpoint. Although inhibiting Hsl7 delayed
      mitosis, Hsl7 overexpression overrode the replication checkpoint, accelerating
      Wee1 destruction. Replication checkpoint activation disrupted Hsl7-Wee1
      interactions, but binding was restored by active polo-like kinase. These data
      establish Hsl7 as a component of the replication checkpoint and reveal that
      similar cell cycle control modules can be co-opted for use by distinct
      checkpoints in different organisms.

PMID- 15583030
TI  - Functional specialization within a vesicle tethering complex: bypass of a subset
      of exocyst deletion mutants by Sec1p or Sec4p.
AB  - The exocyst is an octameric protein complex required to tether secretory vesicles
      to exocytic sites and to retain ER tubules at the apical tip of budded cells.
      Unlike the other five exocyst genes, SEC3, SEC5, and EXO70 are not essential for
      growth or secretion when either the upstream activator rab, Sec4p, or the
      downstream SNARE-binding component, Sec1p, are overproduced. Analysis of the
      suppressed sec3Delta, sec5Delta, and exo70Delta strains demonstrates that the
      corresponding proteins confer differential effects on vesicle targeting and ER
      inheritance. Sec3p and Sec5p are more critical than Exo70p for ER inheritance.
      Although nonessential under these conditions, Sec3p, Sec5p, and Exo70p are still
      important for tethering, as in their absence the exocyst is only partially
      assembled. Sec1p overproduction results in increased SNARE complex levels,
      indicating a role in assembly or stabilization of SNARE complexes. Furthermore, a
      fraction of Sec1p can be coprecipitated with the exoycst. Our results suggest
      that Sec1p couples exocyst-mediated vesicle tethering with SNARE-mediated docking
      and fusion.

PMID- 15583031
TI  - Vesicles carry most exocyst subunits to exocytic sites marked by the remaining
      two subunits, Sec3p and Exo70p.
AB  - Exocytosis in the budding yeast Saccharomyces cerevisiae occurs at discrete
      domains of the plasma membrane. The protein complex that tethers incoming
      vesicles to sites of secretion is known as the exocyst. We have used
      photobleaching recovery experiments to characterize the dynamic behavior of the
      eight subunits that make up the exocyst. One subset (Sec5p, Sec6p, Sec8p, Sec10p,
      Sec15p, and Exo84p) exhibits mobility similar to that of the vesicle-bound Rab
      family protein Sec4p, whereas Sec3p and Exo70p exhibit substantially more
      stability. Disruption of actin assembly abolishes the ability of the first subset
      of subunits to recover after photobleaching, whereas Sec3p and Exo70p are
      resistant. Immunogold electron microscopy and epifluorescence video microscopy
      indicate that all exocyst subunits, except for Sec3p, are associated with
      secretory vesicles as they arrive at exocytic sites. Assembly of the exocyst
      occurs when the first subset of subunits, delivered on vesicles, joins Sec3p and
      Exo70p on the plasma membrane. Exocyst assembly serves to both target and tether
      vesicles to sites of exocytosis.

PMID- 15583032
TI  - Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted
      in osteosarcoma.
AB  - The molecular basis for the inverse relationship between differentiation and
      tumorigenesis is unknown. The function of runx2, a master regulator of osteoblast
      differentiation belonging to the runt family of tumor suppressor genes, is
      consistently disrupted in osteosarcoma cell lines. Ectopic expression of runx2
      induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and
      leading to the dephosphorylation of the retinoblastoma tumor suppressor protein
      (pRb) and a G1 cell cycle arrest. Runx2 physically interacts with the
      hypophosphorylated form of pRb, a known coactivator of runx2, thereby completing
      a feed-forward loop in which progressive cell cycle exit promotes increased
      expression of the osteoblast phenotype. Loss of p27KIP1 perturbs transient and
      terminal cell cycle exit in osteoblasts. Consistent with the incompatibility of
      malignant transformation and permanent cell cycle exit, loss of p27KIP1
      expression correlates with dedifferentiation in high-grade human osteosarcomas.
      Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is
      mediated through runx2 and p27KIP1, and these processes are disrupted in
      osteosarcoma.

PMID- 15583033
TI  - Neuronal membrane cholesterol loss enhances amyloid peptide generation.
AB  - Recent experimental and clinical retrospective studies support the view that
      reduction of brain cholesterol protects against Alzheimer's disease (AD).
      However, genetic and pharmacological evidence indicates that low brain
      cholesterol leads to neurodegeneration. This apparent contradiction prompted us
      to analyze the role of neuronal cholesterol in amyloid peptide generation in
      experimental systems that closely resemble physiological and pathological
      situations. We show that, in the hippocampus of control human and transgenic
      mice, only a small pool of endogenous APP and its beta-secretase, BACE 1, are
      found in the same membrane environment. Much higher levels of BACE 1-APP
      colocalization is found in hippocampal membranes from AD patients or in rodent
      hippocampal neurons with a moderate reduction of membrane cholesterol. Their
      increased colocalization is associated with elevated production of amyloid
      peptide. These results suggest that loss of neuronal membrane cholesterol
      contributes to excessive amyloidogenesis in AD and pave the way for the
      identification of the cause of cholesterol loss and for the development of
      specific therapeutic strategies.

PMID- 15583034
TI  - Ameloblastin is a cell adhesion molecule required for maintaining the
      differentiation state of ameloblasts.
AB  - Tooth morphogenesis results from reciprocal interactions between oral epithelium
      and ectomesenchyme culminating in the formation of mineralized tissues, enamel,
      and dentin. During this process, epithelial cells differentiate into enamel
      secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by
      differentiating ameloblasts. Here, we report the creation of ameloblastin-null
      mice, which developed severe enamel hypoplasia. In mutant tooth, the dental
      epithelium differentiated into enamel-secreting ameloblasts, but the cells were
      detached from the matrix and subsequently lost cell polarity, resumed
      proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were
      deregulated in mutant ameloblasts, the phenotypes of which were reversed to
      undifferentiated epithelium. We found that recombinant ameloblastin adhered
      specifically to ameloblasts and inhibited cell proliferation. The mutant mice
      developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is
      a cell adhesion molecule essential for amelogenesis, and it plays a role in
      maintaining the differentiation state of secretory stage ameloblasts by binding
      to ameloblasts and inhibiting proliferation.

PMID- 15583035
TI  - A maternal blood-borne factor promotes survival of the developing thalamus.
AB  - In this report, we describe the identification of a polypeptide survival
      promoting factor that is produced by maternal and early postnatal peripheral
      blood mononuclear cells (PBMCs) of the immune system in Long-Evans rats and
      humans. The factor, termed Y-P30, most likely arises from proteolytic processing
      of a larger precursor protein and accumulates mainly in pyramidal neurons of the
      developing cortex and hippocampus but not in astrocytes. It was released from
      neurons grown in culture and substantially promotes survival of cells in explant
      monocultures of perinatal thalamus from the offspring. Y-P30 mRNA was not
      detectable in infant or adult brain and was present only in blood cells of
      pregnant rats and humans but not in nonpregnant controls. However, Y-P30
      transcription could be induced in PBMCs of adult animals by a central nervous
      system lesion (i.e., optic nerve crush), which points to a potential role of the
      factor not only in neuronal development but also in neuroinflammation after white
      matter injury.

PMID- 15583036
TI  - Gene expression profiling of muscle tissue in Brahman steers during nutritional
      restriction.
AB  - Expression profiling using microarrays allows for the detailed characterization
      of the gene networks that regulate an animal's response to environmental
      stresses. During nutritional restriction, processes such as protein turnover,
      connective tissue remodeling, and muscle atrophy take place in the skeletal
      muscle of the animal. These processes and their regulation are of interest in the
      context of managing livestock for optimal production efficiency and product
      quality. Here we expand on recent research applying complementary DNA (cDNA)
      microarray technology to the study of the effect of nutritional restriction on
      bovine skeletal muscle. Using a custom cDNA microarray of 9,274 probes from
      cattle muscle and s.c. fat libraries, we examined the differential gene
      expression profile of the LM from 10 Brahman steers under three different dietary
      treatments. The statistical approach was based on mixed-model ANOVA and model
      based clustering of the BLUP solutions for the gene x diet interaction effect.
      From the results, we defined a transcript profile of 156 differentially expressed
      array elements between the weight loss and weight gain diet substrates. After
      sequence and annotation analyses, the 57 upregulated elements represented 29
      unique genes, and the 99 downregulated elements represented 28 unique genes. Most
      of these co-regulated genes cluster into groups with distinct biological function
      related to protein turnover and cytoskeletal metabolism and contribute to our
      mechanistic understanding of the processes associated with remodeling of muscle
      tissue in response to nutritional stress.

PMID- 15583037
TI  - Assessment of single nucleotide polymorphisms in genes residing on chromosomes 14
      and 29 for association with carcass composition traits in Bos indicus cattle.
AB  - Objective of this study was to assess the association of SNP in the
      diacylglycerol O-acyltransferase 1 (DGAT1), thyroglobulin (TG), and micromolar
      calcium-activated neutral protease (CAPN1) genes with carcass composition and
      meat quality traits in Bos indicus cattle. A population of Brahman calves (n =
      479) was developed in central Florida from 1996 to 2000. Traits analyzed were
      ADG, hip height, slaughter weight, fat thickness, HCW, marbling score, LM area,
      estimated KPH fat, yield grade, retail yield, sensory panel tenderness score,
      carcass hump height, and cooked meat tenderness measured as Warner-Bratzler shear
      force at 7, 14, and 21 d postmortem. Single nucleotide polymorphisms previously
      reported in the TG and DGAT1 genes were used as markers on chromosome 14. Two
      previously reported and two new SNP in the CAPN1 gene were used as markers on
      chromosome 29. One SNP in CAPN1 was uninformative, and another one was associated
      with tenderness score (P < 0.05), suggesting the presence of variation affecting
      meat tenderness. All three informative SNP at the CAPN1 gene were associated with
      hump height (P < 0.02). The TG marker was associated with fat thickness and LMA
      (P < 0.05), but not with marbling score. No significant associations of the SNP
      in the DGAT1 gene were observed for any trait. Allele frequencies of the SNP in
      TG and CAPN1 were different in this Brahman population than in reported allele
      frequencies in Bos taurus populations. The results suggest that the use of
      molecular marker information developed in Bos taurus populations to Bos indicus
      populations may require development of appropriate additional markers.

PMID- 15583038
TI  - Polymorphisms in the bovine leptin promoter associated with serum leptin
      concentration, growth, feed intake, feeding behavior, and measures of carcass
      merit.
AB  - Leptin is the hormone product of the obese gene synthesized and secreted
      predominantly by white adipocytes. It functions as a lipostatic signal regulating
      BW, food intake, energy expenditure, reproduction, and certain immune system
      functions. Although previous studies have identified polymorphisms in the coding
      regions of the leptin gene in cattle that show considerable associations with
      feed intake, milk quality and quantity, and carcass fatness, no such associations
      have been reported for the leptin promoter. The current study reports
      associations between SNP in the 5' untranslated promoter region of the bovine
      leptin gene with serum leptin concentration, growth, BW, feed intake, feeding
      behavior, and carcass merit in hybrid cattle (n = 150). The study showed that
      animals with the TT genotype of a less frequent cytosine/thymine (C/ T)
      substitution (UASMS2; frequency of thymine allele equals 0.21) detected at
      position 528 in the bovine leptin promoter (GenBank Accession No. AB070368) show
      48 and 39% increases in serum leptin concentration (P < 0.001), 39 and 31%
      increases in backfat thickness (P < 0.001), and 13 and 9% increase in marbling
      score (P = 0.01), compared with CC or CT genotypes, respectively. Animals with
      the TT genotype also show significantly higher feed intake (P < 0.001), growth
      rate, metabolic BW (P < 0.05), and live weight at slaughter (P < 0.10). Animals
      with the GG genotype of a more frequent cytosine/guanine (C/G) substitution
      (UASMS3; frequency of G allele equals 0.59) at position 1759 in the bovine leptin
      promoter (GenBank Accession No. AB070368) also show higher feed intake (P =
      0.001), growth rate (P < 0.10), and BW (P < 0.01). The thymine allele of UASMS2
      and the guanine allele of UASMS3 were separately associated with higher feeding
      duration (P < 0.05). The two SNP show significant linkage disequilibrium and
      could also be relevant in predicting other characteristics, such as milk yield
      and quality in cattle. These results, however, represent the initial associations
      of the polymorphisms with these traits, and further efforts are required to
      validate these findings in other populations.

PMID- 15583039
TI  - A practical longitudinal model for evaluating growth in Gelbvieh cattle.
AB  - Genetic evaluation of growth in Gelbvieh beef cattle was examined by multiple
      trait (MTM) and random regression (RRM) analysis. The data set comprised 541,108
      animals with 1,120,086 records. Approximately 15% of the animals in the data set
      had at least one record measured outside of the accepted MTM age ranges for
      weaning weight (Wwt) and yearling weight (Ywt). Fourteen percent of Wwt records
      and 19% of Ywt records were measured outside the accepted ranges for MTM
      analysis, and thus were excluded from MTM evaluations. Two RRM evaluations were
      performed using cubic Legendre polynomials (RRML) and linear splines (RRMS) with
      three knots at 1, 205, and 365 d of age. Data Set 1 (d1) utilized all available
      records, whereas Data Set 2 (d2) included only records measured within MTM ranges
      (1 d, 160 to 250 d, and 320 to 410 d). The RRML models did not reach convergence
      until diagonalization was imposed. After diagonalization, it was found that all
      longitudinal models required fewer iterations to converge than the MTM.
      Correlations between the MTM, RRML-d2, and RRMS-d2 evaluations were >or=0.99 for
      all three traits, indicating that these models were equivalent when predicting
      breeding values from data within the MTM age ranges. Correlations between MTM,
      RRML-d1, and RRMS-d1 were >0.99 for Bwt and >0.95 for Wwt and Ywt. The lower
      correlations for Wwt and Ywt indicate that the added information does affect
      breeding value prediction. The RRM has the capability to incorporate records
      measured at all ages into genetic evaluations at a computing cost similar to the
      MTM.

PMID- 15583040
TI  - Incidence of splayleg pigs in Nebraska litter size selection lines.
AB  - Genetic parameters for the splayleg (SL) condition were estimated from 37,673
      records of pigs from six lines derived from a Large White-Land-race base
      population. Random selection for 22 generations was practiced in Lines C1 and C2.
      Line C2 was derived from C1 at Generation 8. Selection lines were as follows: 1)
      Line I, selected 11 generations for an index of ovulation rate and embryonic
      survival followed by 11 generations of selection for litter size; 2) Line IOL,
      derived from Line I at Generation 8 and which underwent eight generations of two
      stage selection for ovulation rate and number of fully formed pigs per litter
      followed by four generations of litter size selection; 3) Line COL, derived from
      Line C1 at Generation 8 and selected eight generations in two stages for
      ovulation rate and number of fully formed pigs followed by four generations of
      litter size selection; and 4) Line T, selected 12 generations for increased
      testis size. From logistic models, it was found that boars were 224% more likely
      to have SL than gilts (P < 0.01). Decreases in birth weight, dam age at puberty,
      dam nipple number, and dam embryonic survival, and increases in dam litter size
      and inbreeding increased the odds of SL (P < 0.05). Direct and maternal
      heritabilities of SL were 0.07 and 0.16, respectively, and the correlation
      between direct and maternal effects was -0.24. Correlations between direct
      genetic effects for SL and number born alive, nipple number, birth weight, age at
      puberty, and embryonic survival were -0.19, -0.36, 0.23, -0.19, and -0.32,
      respectively. Except for the correlation of 0.32 between maternal effects for SL
      and direct effects for number of live pigs, correlations of SL maternal genetic
      effects with direct genetic effects of other traits were less than 0.11. Annual
      direct genetic trends (%) for SL in I, IOL, COL, T, C1, and C2 were -0.003 +/-
      0.003, 0.121 +/- 0.012, -0.273 +/-0.009, 0.243 +/-0.014, -0.274 +/-0.004, and
      0.086 +/-0.008, respectively; annual maternal genetic trends (%) were 0.106 +/
      0.004, 0.508 +/-0.019, 0.383 +/-0.015, 0.527 +/-0.024, 0.188 +/-0.005, and 0.113
      +/-0.012, respectively. Annual genetic maternal trend in Line I after Generation
      12 was 0.339 +/-0.014. Maternal breeding value for SL is expected to increase as
      a correlated response to selection for increased litter size and increased size
      of testes.

PMID- 15583041
TI  - Genetic analysis of age at first service, return rate, litter size, and weaning
      to-first service interval of gilts and sows.
AB  - The aim of this study was to estimate genetic parameters of seven traits related
      to sow reproductive performance. Data on all Norwegian Landrace pigs (NL) born in
      nucleus herds and raised in nucleus or multiplying herds from 1990 to 2000 were
      extracted from the Norwegian national recording scheme. Reproductive traits
      investigated were age at first service (AFS), return rate in gilts (RRg), age at
      first farrowing (AFF), live-born piglets in the first litter (NBA1), interval
      from weaning to first service after first litter (WTS1), return rate after first
      litter (RR1), live-born piglets in the second litter (NBA2), and interval from
      weaning to first service after second litter (WTS2). After editing, the data set
      comprised 12,583 to 56,042 records, depending on the trait. A mixed linear and a
      joint linear threshold animal model were used to estimate (co)variance
      components. A full Bayesian approach via Gibbs sampling was adopted. The
      statistical model used for analysis included contemporary groups of herd-year (
      season), purebred or crossbred litter, single or double insemination, mating
      type, parity in which the animal was born, a regression on lactation length, and
      an additive genetic effect. Neither the estimated heritabilities nor the genetic
      correlations differed much between the two approaches, but there was a tendency
      for higher genetic correlations using the joint linear threshold model approach.
      Average heritabilities were as follows: AFS = 0.31; RRg = 0.03; RR1 = 0.02; NBA1
      = 0.12; NBA2 = 0.14; WTS1 = 0.08; and WTS2 = 0.03. The highest genetic
      correlations were estimated between NBA1 and NBA2 (r(g) = 0.95), RR1 and WTS1
      (r(g) = 0.93), and between WTS1 and WTS2 (r(g) = 0.78). The estimated genetic
      correlation between NBA and WTS were close to zero. Selection for increased NBA
      will slightly increase AFS and reduce the probability of a return. Selection for
      decreased AFS will have a favorable effect on WTS intervals; however, selection
      for decreased AFS seems to have an unfavorable effect on return rate both on
      gilts and sows. Conversely, selection for decreased WTS intervals will reduce the
      probability of a return. Potential selection candidates to include in a
      multivariate fertility index are AFS, NBA, and WTS1. Due to the low heritability
      and low, but favorable, genetic correlations to NBA and WTS, RR is not
      recommended as a selection candidate.

PMID- 15583042
TI  - Effects of genotype x environment interaction on genetic gain in breeding
      programs.
AB  - Genotype x environment interaction (G x E) is increasingly important, because
      breeding programs tend to be more internationally oriented. The aim of this
      theoretical study was to investigate the effects of G x E on genetic gain in sib
      testing and progeny-testing schemes. Loss of genetic gain due to G x E was
      predicted for different values of heritability, number of progeny per dam, number
      of progeny per sire, proportion of selected sires, and population size in the
      selection environment. Two environments were considered: a selection environment
      (SLE) and a production environment (PDE). The breeding goal was only for
      performance in PDE. A pseudo-BLUP selection index was used to predict genetic
      gain. Recording of half-sibs or progeny in PDE limited the loss in genetic gain
      in PDE due to G x E between SLE and PDE. Progeny-testing schemes had less loss in
      genetic gain than sib-testing schemes. Higher heritability increased the loss in
      genetic gain, whereas increasing the number of progeny per sire in PDE decreased
      the loss in genetic gain. The number of progeny per sire required to minimize
      loss in genetic gain due to G x E was greater for sib-testing schemes than for
      progeny-testing schemes. More progeny per dam slightly increased the loss in
      genetic gain. Genetic gains for sex-limited and carcass traits were less affected
      by G x E than traits measured on both sexes. Loss in genetic gain was due to
      decreased accuracy of selection in most situations, but it was due to decreased
      selection intensity in situations with small population size and a low proportion
      of selected sires. It was concluded that recording performance of relatives in
      PDE minimizes loss in genetic gain due to G x E, and that progeny-testing schemes
      rather than sib-testing schemes are preferable in situations with low to moderate
      heritability (h(2) <or= 0.3), relatively short generation interval of progeny
      tested sires (L(prog)/L(sib) <or= 1.7), and moderate to severe G x E interaction
      (r(g) <or= 0.8).

PMID- 15583043
TI  - Studies on multiple trait and random regression models for genetic evaluation of
      beef cattle for growth.
AB  - A simulation study examined issues important for genetic evaluation of growth in
      beef cattle by random regression models with cubic Legendre polynomials (RRML)
      and linear splines with three knots (RRMS) compared with multiple-trait models
      (MTM). Parameters for RRML were obtained by conversion from covariance functions.
      Parameters for MTM and RRMS were extracted from RRML at 1, 205, and 365 d;
      parameters for RRMS were the same as MTM for all effects except the permanent
      environment and the residual. Four data sets were generated assuming RRML
      included records at 1, 205, and 365 d; at 1, 160 to 250, and 320 to 410 d; at 1,
      100, 205, 300, and 365 d; and at 1, 55 to 145, 160 to 250, 275 to 325, and 320 to
      410 d. Accuracies were computed as correlations between the true (simulated) and
      predicted breeding values. With the first data set, excellent agreement in
      accuracy was obtained for all models. With the second data set, the accuracy of
      MTM dropped by up to 1.5% compared with the first data set, but accuracy was
      unchanged for both RRML and RRMS. With the third (fourth) data set, accuracies of
      RRML were up to 2.4% (2.5%) higher than with the first (second) data set. Small
      differences in accuracy between RRML and RRMS were found with the third and
      fourth data sets, which were traced to inflated correlations especially between 1
      and 205 d in RRMS; inflation could be decreased by adding one extra knot at 100 d
      to RRMS. Diagonalization of random coefficients was crucial for RRML but not for
      RRMS, resulting in approximately six (two) times faster convergence with RRML
      (RRMS). Reduction of dimensionality in RRML associated with small eigenvalues
      caused a less accurate evaluation for birth weight. Genetic evaluation of growth
      by RRM requires careful implementation. The RRMS is simpler to implement than the
      RRML.

PMID- 15583044
TI  - Unexpected estimates of variance components with a true model containing genetic
      competition effects.
AB  - Simulation of a model containing genetic competition effects was initiated to
      determine how well REML could untangle variances due to direct and competition
      genetic effects and pen effects. A two-generation data set was generated with six
      unrelated males that were each mated to five unrelated females to produce 300
      progeny, from which 30 females (one per mating in previous generation) were mated
      to six unrelated males to produce 300 more progeny. Progeny were randomly
      assigned, six per pen, to 50 pens per generation. Parameters were V(g), V(c),
      C(gc), V(p), and V(e), representing direct and competition genetic variance with
      covariance, and pen and residual variance. Eight statistical models were used to
      analyze each of 400 replicates of 16 sets of parameters. Both V(g) and V(e) were
      fixed at 16.0. Values of C(gc) were -2.0, -1.0, 0.1, 1.0, and 2.0. Values of V(c)
      were 1.0 and 4.0, and values of V(p) were 0.1, 1.0, and 10.0. With the full
      model, average estimates resembled true parameters, except that V(p) was
      consistently overestimated when small (0.1 and 1.0), which in turn slightly
      changed other estimates. The most unexpected result was overestimation of V(p)
      when V(c) and Cgc were ignored. Overestimation depended on V(c) and the number of
      competitors in common between records in a pen. Upward bias was somewhat greater
      when Cg(c) was positive than when it was negative. For example, with C(gc) = 2,
      V(c) = 4, and V(p) = 0.1, the mean estimate of V(p) was 20.4 when C(gc) and V(c)
      were dropped from the model and 15.3 when C(gc) = -2.0. When V(p) was ignored,
      estimates of both C(gc) and V(c) increased in proportion with V(p). Also V(g)
      increased more with greater V(p). Another unexpected result occurred when pen was
      considered fixed. Empirical sampling standard errors of estimates of C(gc) and
      V(c) were decreased generally by factors of 2 to 30. Based on these results, we
      conclude a high estimate of pen variance may indicate genetic competition effects
      are important, and ignoring either the pen or competition effects will bias
      estimates of other components.

PMID- 15583045
TI  - Effects of dietary supplementation with L-carnitine and fat on blood acid-base
      responses to handling in slaughter weight pigs.
AB  - Blood acid-base responses to handling were evaluated in slaughter weight pigs fed
      diets supplemented with l-carnitine and fat. The study was carried out as a
      randomized block design with a 2 x 2 factorial arrangement of treatments: 1)
      dietary L-carnitine supplementation (0 vs. 150 ppm, as-fed basis); and 2) dietary
      fat supplementation (0 vs. 5%, as-fed basis). Sixty pigs (91.1 +/- 5.14 kg BW)
      were housed in mixed-gender groups of five and had ad libitum access to test
      diets (0.68% true ileal digestible lysine, 3,340 kcal of ME/kg, as-fed basis) for
      3 wk. At the end of the feeding period (110.3 +/- 7.52 kg BW), pigs were
      subjected to a standard handling procedure, which consisted of moving individual
      animals through a facility (12.2 m long x 0.91 m wide) for eight laps (up and
      down the facility), using electric prods (two times per lap). There was no
      interaction between dietary L-carnitine and fat supplementation for any
      measurement. Pigs fed 150 ppm of supplemental L-carnitine had lower baseline
      blood glucose (P < 0.05) and higher baseline blood lactate (P < 0.05)
      concentrations than the nonsupplemented pigs. After handling, pigs fed L
      carnitine-supplemented diets had a higher (P < 0.05) blood pH and showed a
      smaller (P < 0.05) decrease in blood pH and base excess than those fed the
      nonsupplemental diets. Baseline plasma FFA concentrations were higher (P < 0.01)
      in pigs fed the 5% fat diet. After the handling procedure, blood glucose,
      lactate, and plasma FFA were higher (P < 0.05) in pigs fed the 5 vs. 0% fat
      diets, but blood pH, bicarbonate, and base excess were not affected by dietary
      fat. The handling procedure decreased (P < 0.01) blood pH, bicarbonate, base
      excess, and total carbon dioxide and increased (P < 0.01) blood lactate, partial
      pressure of oxygen, and glucose, and also increased (P < 0.01) rectal
      temperature. Free fatty acid concentrations were increased by handling in pigs
      fed both 0 and 5% fat and 150 ppm L-carnitine. In conclusion, dietary L-carnitine
      supplementation at the level and for the feeding period evaluated in the current
      study had a relatively small but positive effect on decreasing blood pH changes
      in finishing pigs submitted to handling stress; however, dietary fat
      supplementation had little effect on blood acid-base balance.

PMID- 15583046
TI  - Effects of dietary quillaja saponin and curcumin on the performance and immune
      status of weaned piglets.
AB  - The objective of this study was to determine whether dietary quillaja saponin and
      curcumin (extract of turmeric) can modify piglet immune status and performance
      immediately after weaning. Piglets (n = 192) were weaned at 29 +/- 0.1 d and
      allocated to treatment (six replicates of eight pig per treatment) accounting for
      weight, litter, and gender, using a 2 x 2 factorial arrangement. Factors were
      diets with or without (as-fed basis) quillaja saponin (750 mg/kg during wk 1, 300
      mg/kg during wk 2 to 3) and with or without dietary curcumin (200 mg/kg). Diets
      were fed ad libitum for 20 d after weaning. Feed intake was measured daily.
      Piglets were weighed at weaning, d 7, 14, and 20 after weaning. On each of d 6
      and 20 after weaning, eight pigs per treatment were sacrificed for blood and
      tissue collection. Treatment had no effect on piglet growth. The ADFI and G:F
      were similar for all treatments between d 0 and 14 of the trial. Between d 15 and
      20, ADFI and G:F were lower in quillaja-supplemented piglets (ADFI = 621 vs. 572
      g/d; G:F = 0.75 vs. 0.85; P < 0.05). Serum immunoglobulin (Ig) G, IgA, interferon
      gamma, and C-reactive protein (CRP) did not differ among treatments on d 6 after
      weaning. On d 20, IgG and CRP were greater (P < 0.05) in saponin-supplemented
      pigs (IgG = 17.5 vs. 11.4 mg/mL; CRP = 26.98 vs. 12.5 mg/mL). Small intestine
      villus and crypt measurements did not differ among treatments on either d 6 or
      20. Saponin supplementation during the postweaning period seemed to potentiate an
      immune response in the weaned piglet but had a detrimental effect on the
      utilization of feed. Dietary curcumin had no influence on any measured aspect of
      pig performance or immune status.

PMID- 15583047
TI  - Butyrate-induced apoptosis and cell cycle arrest in bovine kidney epithelial
      cells: involvement of caspase and proteasome pathways.
AB  - Beyond their nutritional effect, short-chain fatty acids, especially butyrate,
      modulate cell differentiation, proliferation, motility, and in particular, they
      induce cell cycle arrest and apoptosis. A bovine kidney epithelial cell line
      (Madin-Darby bovine kidney; MDBK) was used to investigate the cell cycle
      regulatory and apoptotic effects of butyrate. Butyrate not only induced apoptosis
      but also induced cell cycle arrest at the G1/S boundary and M/G2 in MDBK cells (P
      < 0.01). The cell responses were concentration-dependent (r(2) = 0.9482, P
      <0.001). In examining possible mechanisms for the apoptosis and cell cycle arrest
      induced by butyrate, the results showed that butyrate treatment activates caspase
      3 activities and induces accumulation of acetylated histone. At least two
      proteins, cdc6 and cdk1, become targeted for destruction on butyrate treatment.
      These two proteins are downregulated (P < 0.01 and P < 0.05, respectively) by
      proteolytic pathways. Moreover, the proteasome inhibitor MG-132 (carbobenzoxy-L
      leucyl-L-leucyl-L-leucinal) reverses the cell cycle arrest induced by butyrate,
      indicating a multiprotein crosstalk wherein the ubiquitination/ proteasome
      pathway interacted with the caspase-signaling pathway. Because the proteasome
      inhibitor MG-132 blocked activation of caspase-3, these results functionally
      locate the proteasome pathway upstream of the caspase pathway. All these results
      indicate that butyrate functions as both a nutrient and signaling molecule
      regulating cell growth and proliferation.

PMID- 15583048
TI  - Regulation of differentiating pig preadipocytes by retinoic acid.
AB  - All-trans retinoic acid (ATRA) potently inhibits the differentiation of porcine
      preadipocytes in primary culture; however, the mechanism by which ATRA exerts
      this effect in pigs is poorly understood. The objective of this study was to use
      retinoid receptor-specific ligands to investigate the mechanism underlying the
      antiadipogenic action of retinoids in cultured pig preadipocytes by identifying
      the retinoid receptor mediating this action and examining the effect of retinoids
      on the expression of key adipogenic transcription factors. Stromal-vascular cells
      were harvested from porcine adipose tissue and cultured in serum-free medium.
      Glycerol-3-phoshphate dehydrogenase (GPDH) activity, a late marker of
      preadipocyte differentiation, was decreased (P < 0.01) by the addition of 0 to 10
      microM of either ATRA, a nonspecific agonist for both the retinoic acid receptor
      (RAR) and the retinoid X receptor (RXR) or the selective RAR agonist, 4-(E-2
      [5,6,7,8-tet-rahydro-5,5,8,8-tetramethyl-2-naphthalenyl]-1-propenyl) benzoic acid
      (TTNPB). Addition of increasing amounts of Ro-61, a RAR-specific antagonist (0 to
      10 microM) prevented ATRA and TTNBP from decreasing GPDH activity. Addition of
      methoprene acid, an RXR-specific agonist, increased (P < 0.01) GPDH activity.
      Preadipocytes were then continuously treated with 10 nM of TTNPB in the presence
      or absence of 1 microM Ro-61, and mRNA was isolated on d 2 and 8. Addition of
      TTNPB decreased (P < 0.001) the expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma), sterol regulatory element-binding protein-1c (SREBP
      1c), retinoid X receptor alpha (RXRalpha), and adipocyte fatty acid binding
      protein (aP2) mRNA transcripts, whereas these effects were prevented by the
      presence of Ro-61. Interestingly, TTNBP increased (P < 0.001) the mRNA abundance
      of the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription
      factor 1 (COUP-TF1), whereas Ro-61 prevented this increase. These changes were
      independent of alterations in the mRNA abundances of the retinoic acid receptor
      alpha, and CCAAT/enhancer binding protein alpha and beta (C/EBPbeta; C/EBPalpha)
      genes. These results indicate that retinoic acid inhibits porcine preadipocyte
      differentiation by a mechanism that involves activation of the RAR and
      downregulation of PPARgamma, RXRalpha, and SREBP-1C mRNA. This mechanism is
      independent of changes in C/EBPbeta and C/EBPalpha mRNA abundance and may involve
      COUP-TF.

PMID- 15583049
TI  - The effect of stage of growth and implant exposure on performance and carcass
      composition in steers.
AB  - Angus and Angus x Limousin cross steers (n = 182; initial BW = 309 +/- 27.8 kg)
      were used to evaluate the influence of an estradiol-trenbolone acetate implant
      (containing 24 mg of estradiol and 125 mg of trenbolone acetate) on production
      efficiency and carcass traits when administered at specific stages of growth.
      Treatments were 1) control, no implant (NI); 2) early implant (EI) on d 1 (BW =
      309 kg); or 3) delayed implant (DI) on d 57 (BW = 385 kg). Comparisons were also
      made between the NI and implanted treatments (I; EI + DI). Steers were procured
      at weaning and were backgrounded (47 d) before the initiation of the experiment.
      Initial predicted carcass composition was 14.9% protein, 13.3% fat, 54.6%
      moisture, and 17.2% bone. Days on feed were constant across treatment. After 56
      d, ADG and G:F were improved (P < 0.01) by implants, NI vs. EI (1.68 vs. 1.90 kg
      and 0.227 vs. 0.257). At d 57, predicted carcass composition did not differ among
      treatments. From 57 to 112 d, DI caused higher ADG than NI or EI (NI = 1.65, EI =
      1.57, and DI = 1.78 kg; P < 0.05) and higher G:F (NI = 0.155, EI = 0.150, and DI
      = 0.173; P < 0.01). Cumulative ADG and G:F were improved by implants (1.65 vs.
      1.73 kg; P < 0.05) and (0.175 vs. 0.186; P < 0.01) for NI vs. I, respectively,
      with no differences between treatments that involved implants. Cumulative DMI was
      similar for all treatments. Implanting increased dressing percentage (63.5 vs.
      64.1%; P < 0.05) and increased (P < 0.01) hot carcass weight (341 vs. 353 kg) and
      LM area (76.5 vs. 81.4 cm(2)) for NI vs. I, respectively. Rib fat and kidney,
      pelvic, and heart fat were not affected by treatment, and treatment had no effect
      on the whole carcass proportions of fat, protein, or water. Implants advanced
      maturity scores (NI = A(51) vs. EI + DI = A(59); P < 0.01). Marbling scores were
      decreased (P < 0.05) by EI but not by DI (NI = Small(65), EI = Small(20), DI =
      Small(36)). The percentage of i.m. fat content of the LM was decreased (P < 0.10)
      by EI and was not affected by DI (NI = 5.1, EI = 4.0, DI = 4.8%). Treatment
      affected (P < 0.10) the proportion of carcasses with marbling scores greater than
      Modest(0) (NI = 23.6, EI = 7.8, DI = 22.6%). The results of this study suggest
      that growth of i.m. fat is sensitive to anabolic growth promotants administered
      during early periods of growth.

PMID- 15583050
TI  - Nutrient restriction differentially modulates the mammalian target of rapamycin
      signaling and the ubiquitin-proteasome system in skeletal muscle of cows and
      their fetuses.
AB  - The mammalian target of rapamycin (mTOR) signaling controls nutrient-stimulated
      protein synthesis in skeletal muscle, whereas ubiquitin-proteasome systems
      control the degradation of myofibrillar proteins. The objective of this study was
      to elucidate the effect of nutrient restriction on the mTOR signaling and
      ubiquitin-proteasome system in the skeletal muscle of cows and their fetuses.
      Beginning 30 d after conception, 20 cows were fed either a control diet that
      provided 100% nutrient requirements or a nutrient-restricted diet at 68.1% of
      NE(m) and 86.7% of metabolizable protein requirement. Cows were slaughtered on
      125 d of gestation, and the LM of both cows and fetuses was sampled for the
      measurement of mTOR, ribosomal protein S6, adenosine 5'-monophosphate-activated
      protein kinase (AMPK), and protein ubiquitylation. When comparing the muscle
      samples from nutrient-restricted and control cows and their fetuses, no
      difference was observed for the content of mTOR and ribosomal protein S6, but the
      phosphorylation of mTOR at Ser(2448) and ribosomal protein S6 at Ser(235/336)
      were greater (P < 0.05) in control muscle than in muscle from nutrient-restricted
      animals. Because the phosphorylation of mTOR and ribosomal protein S6 upregulates
      translation, these results showed that nutrient restriction inhibits protein
      synthesis in muscle. The activity of AMPK in the muscle of nutrient-restricted
      cows was significantly lower (P = 0.05) than that of control cows. The protein
      ubiquitylation, however, was greater (P < 0.05) in the muscle from nutrient
      restricted cows, showing accelerated protein degradation. No difference in the
      protein ubiquitylation was detected for fetal muscle. Data suggested that the
      decreased protein synthesis and promoted protein degradation resulted in muscle
      atrophy of pregnant cows, but not in fetal muscle. Results of this study show
      that in response to nutrient restriction, protein degradation was differentially
      regulated between cow and fetal muscle. The atrophy of cow muscle during nutrient
      deficiency may involve the enhanced degradation of muscle proteins.

PMID- 15583051
TI  - Preorbital gland opening in red deer (Cervus elaphus) calves: signal of hunger?
AB  - The opening of the preorbital gland in red deer (Cervus elaphus) calves has been
      hypothesized to be a signal to the mother that her calf is hungry. Closing of the
      gland should indicate that the calf has received a sufficient amount of milk, and
      thus the mother should stop the suckling. We tested the hypothesis that the calf
      signals hunger when its preorbital gland is open and signals satiation when the
      gland is closed. To test this, the behavior of eight bottle-reared calves was
      monitored for 6 mo. For each meal during this time period, opening of the
      preorbital gland was recorded before calves were offered the meal and after they
      ate. Satiation of the calf was estimated (not begging for more food after the
      meal = satiated; begging = not satiated). The data set contained 3,116 records of
      paired measurements of preorbital gland opening (before and after the meal).
      Calves were satiated after feeding for 90.15% of the meals. The opening of the
      preorbital gland was associated with feeding and achieving satiety. In most cases
      (77%), calves opened their preorbital glands before their meal. Eighty-five
      percent of hungry calves still had preorbital glands open after the meal, whereas
      preorbital gland opening was decreased (P < 0.03) up to 46.6% in satiated calves.
      Despite this, we found a large range in individual responses in preorbital gland
      opening before and after the meal, and also according to whether the calf reached
      satiety. The heavier calves in this study tended to have their preorbital glands
      open more frequently than the lighter ones, which may indicate the need for an
      increased amount of milk intake. There was no clear trend in the frequency of
      preorbital gland opening with age. In conclusion, preorbital opening is likely to
      be a signal of calf satiety, as suggested earlier. Nevertheless, preorbital
      glands were not always open when the calves were hungry and did not vanish during
      the feeding in all cases.

PMID- 15583052
TI  - Follicular development and maturation in gilts selected for an index of high
      ovulation rate and high prenatal survival.
AB  - Seventy-one 10th-generation gilts from White Line-1 (WL-1 = randomly selected
      control line) and White Line-2 (WL-2 = selected for an index of ovulation rate
      and prenatal survival rate) were used to compare the pattern of follicular
      development and atresia during the follicular phase of the estrous cycle. Gilts
      were treated with PGF(2alpha)on d 13 of the estrous cycle (d 0 of induced
      follicular development) to induce luteolysis and assigned randomly within line
      and sire for ovary recovery on d 0, 2, 3, 4, 5, and the day after estrus. Ovaries
      were evaluated for numbers of corpora albicantia and small (2 to 2.9 mm), medium
      (M1 = 3 to 4.9 mm; M2 = 5 to 6.9 mm), and large (>or=7 mm) follicles. The
      concentration of estradiol-17beta in follicular fluid was used to classify
      individual M2 and large follicles as estrogen-active (>or=100 ng of estradiol
      17beta/mL) or inactive (<100 ng of estradiol-17beta/mL). The WL-2 gilts had a
      greater ovulation rate than WL-1 gilts at their pre-treatment estrus (20.4 vs.
      13.8 corpora albicantia; P < 0.001). The small and M1 follicle populations
      decreased rapidly in both lines over time (P < 0.001). The M2 follicle population
      increased in both lines between d 0 to 4 and then decreased. Mean estradiol
      concentration of M2 follicles increased in both genetic lines over time (P <
      0.02). All large follicles were estrogen-active in both lines; the number of
      large follicles increased with day (P < 0.001) and was similar in both lines. The
      number of estrogen-active M2 follicles was similar in both lines, increasing to d
      3 and 4 and then decreasing (P < 0.01) thereafter. However, the total number of
      estrogen-active follicles (sum of estrogen-active M2 and large follicles) was
      greater in WL-2 than in WL-1 gilts (P < 0.04), increasing to the ovulatory
      potential by d 3 in WL-1 gilts, but continuing to increase through d 4 in WL-2
      gilts. Selection of an additional six ovulatory follicles from the estrogen
      active M2 follicle pool after d 5 was required in both lines to achieve the
      projected ovulation rate, and after estrus, the number of large follicles
      remained insufficient to attain the ovulatory potential of each line.

PMID- 15583053
TI  - A comparison of progestin-based protocols to synchronize ovulation and facilitate
      fixed-time artificial insemination in postpartum beef cows.
AB  - The experimental objective was to compare pregnancy rates after fixed-time AI in
      postpartum suckled beef cows following administration of two progestin-based
      protocols to synchronize ovulation. Cows (n = 424) at three locations (n = 208,
      122, and 92 per location) were stratified by age, BCS, and days postpartum (DPP)
      and assigned randomly to one of the two treatment protocols. The MGA Select
      treated cows (MGA Select; n = 213) were fed melengestrol acetate (MGA, 0.5 mg x
      cow(-1) x d(-1)) for 14 d and carrier for 8 d, and then GnRH (100 microg i.m.
      Cystorelin; d 26) was injected 12 d after MGA withdrawal, and PG (25 mg i.m.
      Lutalyse) was administered 7 d after GnRH. Cows assigned to the 7-11 Synch
      protocol (7-11 Synch; n = 209) were fed carrier for 15 d and MGA for 7 d, and
      then injected with PG on d 22 (d 7 of MGA), GnRH on d 26, and PG again on d 33.
      Artificial insemination was performed at fixed times for cows in both treatments
      at 60 or 72 h after d 33 PG for 7-11 Synch and MGA Select groups, respectively.
      All cows were injected with GnRH (100 microg of i.m. Cystorelin) at AI. There was
      no treatment x location interaction for age (P = 0.90), BCS (P = 0.64), or DPP (P
      = 0.93), and the results were therefore pooled for the respective treatments (age
      [7-11 Synch, 5.5 +/- 0.2; MGA Select, 5.5 +/- 0.2], BCS [7-11 Synch, 5.7 +/- 0.1;
      MGA Select, 5.6 +/- 0.1], and DPP [7-11 Synch, 41.1 +/- 1.1; MGA Select, 42.1 +/-
      1.1]). Blood samples were collected 8 and 1 d before MGA or carrier to determine
      pretreatment estrous cyclicity (progesterone >or=1 ng/mL; 7-11 Synch, 59/209
      [28%]; MGA Select, 54/213 [25%]; P = 0.50) and again on d 33 PG to evaluate
      treatment response as a percentage of cows with progesterone concentrations in
      serum >or=1ng/mL (7-11 Synch, 184/209 [88%]; MGA Select, 177/213 [83%]; P =
      0.15). Pregnancy rates resulting from fixed-time AI did not differ (P = 0.25)
      between treatments (7-11 Synch, 128/209 [61%]; MGA Select, 142/213 [67%]), nor
      did pregnancy rates (P = 0.77) at the end of the breeding season (7-11 Synch,
      198/208 [95%]; MGA Select, 204/213 [96%]). These data indicate that pregnancy
      rates were comparable after fixed-time AI, following administration of the 7-11
      Synch and MGA Select protocols. Both protocols provide opportunities for beef
      producers to use AI and eliminate the need to detect estrus.

PMID- 15583054
TI  - Preweaning piglet mortality in relation to placental efficiency.
AB  - The relationship between placental efficiency (PLEFF, i.e., the ratio of birth
      weight [BWB] to placental weight [PLW]) and neonatal pig vitality as measured by
      the probability of preweaning death of live born piglets was examined for 1,036
      live born piglets of 118 litters. The data were first analyzed to establish
      whether the relationships between PLEFF, PLW, and BWB were affected by parity
      (first vs. higher). Furthermore, the data collected were used to establish
      whether PLEFF is a better predictor of the risk of neonatal pig mortality before
      weaning than BWB and PLW. The relationships of BWB to PLW and PLEFF to PLW
      differed (P <0.01 and P <0.05, respectively) between piglets from gilts and sows.
      This difference appeared to be due mainly to an additional population of piglets
      with very large placentas in sows that were not present in gilts. Despite being
      significant, the courses of the relationships were essentially similar for
      piglets in gilts and in sows. For the curvilinear relationship of BWB to PLW, up
      to a certain threshold value, an increase of PLW resulted in an increase in BWB,
      and thereafter BWB did not change. A consequence of this is that PLEFF at
      relatively high PLW does not give the same information as PLEFF at relatively low
      PLW. For the second-order relationship of PLEFF to BWB, PLEFF increased with an
      increase in BWB, until BWB = 1,657 g, and decreased thereafter. The PLEFF
      decreased linearly with PLW. A change in PLW had a much larger impact on the
      value of PLEFF than a change in BWB. Although BWB and PLW were negatively
      associated with the chance of dying before weaning (P <0.001 and P <0.01,
      respectively), only PLEFF tended to be negatively associated with the chance of
      dying only before weaning (P = 0.08). Its underlying trait, BWB, played a greater
      role on the effect of PLEFF on the chance of preweaning death than PLW. In
      conclusion, PLEFF in swine is a complicated trait that should be treated with
      care. It is merely a mathematical derivative of BWB and PLW, whereby the extent
      to which BWB depends on PLW depends on the value of PLW. Placental functioning
      and fetal growth capacity, however, also have their effects on the value of BWB.
      It is concluded that, of the three traits (BWB, PLW, and PLEFF), the best
      predictor for the chance of preweaning mortality, which also happens to be
      easiest to measure, remains BWB.

PMID- 15583055
TI  - Luteinizing hormone-releasing hormone fusion protein vaccines block estrous cycle
      activity in beef heifers.
AB  - Two LHRH fusion proteins, thioredoxin and ovalbumin, each containing seven LHRH
      inserts were tested for their ability to inhibit estrous cycle activity. The
      objective was to evaluate immune and biological responses from alternating the
      two fusion proteins in an immunization schedule. One hundred ten heifers were
      divided equally into 11 groups. Two control groups consisted of either spayed or
      intact, untreated heifers. Heifers in the other nine groups were immunized on wk
      0, 4, and 9. Treatments were immunizations of the same protein throughout or
      alternating the proteins in different booster sequences. Blood was collected
      weekly for 22 wk, and serum was assayed for concentrations of progesterone and
      titers of anti-LHRH. At slaughter, reproductive tracts were removed from each
      heifer and weighed. Heifers with >or=1 ng/mL of progesterone were considered to
      have a functional corpus luteum and thus to have estrous cycle activity. All LHRH
      immunized groups of heifers had a smaller (P < 0.05) proportion of heifers
      showing estrous cycle activity after 6 wk than the intact, untreated control
      group. There was no difference in number of heifers cycling between the immunized
      groups and the spayed heifers during wk 9 to 22. Anti-LHRH did not differ among
      immunized groups during wk 1 to 9. Starting at wk 10 and continuing through the
      conclusion of the study, there was an overall difference among treatment groups
      for anti-LHRH (P < 0.05). Uterine weights differed among treatments (P < 0.05),
      with intact control animals having heavier uteri than all other groups (P <
      0.05). Uterine weights were negatively correlated with maximum LHRH antibody
      binding (r = -0.44). In summary, the LHRH fusion proteins were as effective as
      surgical spaying in suppression of estrous cycle activity, but alternating the
      two proteins in an immunization schedule did not enhance the immunological or
      biological effectiveness of the vaccine.

PMID- 15583056
TI  - Corn hybrid affects in vitro and in vivo measures of nutrient digestibility in
      dogs.
AB  - Corn is a commonly used ingredient in dry pet foods because there is a stable
      supply and it is a relatively inexpensive source of nutrients. Corn hybrids are
      available that are higher in CP and amylose and lower in phytate concentration
      than conventional hybrids. Approximately 500 mg of high-protein (HP), high
      protein, low-phytate (HPLP), and high-amylose (HA) corn were compared with
      conventional (CONV) corn and amylomaize starch (AM) in triplicate and exposed to
      pepsin/hydrochloric acid and pancreatin to simulate hydrolytic digestion.
      Substrate remaining after this was used to determine in vitro colonic
      fermentation. Organic matter disappearances as a result of hydrolytic digestion
      were >80% for CONV, HP, and HPLP, whereas HA (60.7%) and AM (43.7%) were lower (P
      < 0.05). Total digestion (TD) values after hydrolytic digestion and 8 h of
      fermentation using canine fecal inoculum were greater (P < 0.05) for CONV, HP,
      and HPLP vs. HA and AM. The residue left after hydrolytic digestion of all
      substrates was poorly fermented. Five ileal-cannulated dogs were fed each corn
      hybrid at approximately 31% of the diet in a 5 x5 Latin square design. Dogs fed
      diets containing HP corn had higher (P < 0.05) ileal OM digestibility (70.3%) and
      tended (P < 0.10) to have higher DM digestibility (64.6%). Ileal starch
      digestibilities were lower (P < 0.05) for dogs fed HA (64.0%) and AM (63.0%).
      Ileal digestibilities of essential (71.2%), nonessential (67.4%), and total
      (69.0%) AA tended to be higher (P < 0.10) for HP diets compared with CONV (66.4,
      62.4, and 64.0%, respectively). Total-tract DM, OM, CP, and GE digestibilities
      (77, 82, 77, and 84%, on average, respectively) were higher (P < 0.05) for dogs
      fed CONV, HP, and HPLP than for those fed AM (66.9, 71.6, 72.6, and 76.5%) and HA
      (60.6, 65.7, 69.7, and 71.5%). Total-tract fat digestibilities were lower (P <
      0.05) for dogs fed HA diets (86.6%) than for all other treatments (91.0%, on
      average). Total-tract starch digestibilities were higher (P < 0.05) for dogs fed
      CONV, HP, and HPLP (98%, on average) compared with HA (72.8%) and AM (76.5%). No
      differences were detected among treatments in fecal bifidobacteria, lactobacilli,
      or Clostridium perfringens concentrations. The experiments demonstrated that HP
      and HPLP corn had hydrolytic digestion and fermentation characteristics similar
      to those of CONV corn, whereas HA resulted in similar responses to AM, a well
      established resistant starch ingredient.

PMID- 15583057
TI  - Functional characterization of a cloned pig intestinal peptide transporter
      (pPepT1).
AB  - Absorption of dietary protein can be mediated through the uptake of AA as free AA
      or small peptides. A H(+)-coupled, peptide transport protein, PepT1, is
      responsible for the absorption of small peptides arising from digestion of
      dietary proteins in the small intestine. The magnitude of peptide absorption and
      the nutritional significance of PepT1 are unknown for many food-producing
      animals; thus, the objective of this study was to clone and determine the
      functional characteristics of the pig PepT1 (pPepT1). Two cDNA-encoding pPepT1
      were isolated, which contain alternative polyadenylation sites. The predicted
      pPepT1 is a 708-AA protein, which shows 82.8, 85.7, and 64.7% AA identity to
      human, sheep, and chicken PepT1, respectively. On northern blots, two pPepT1 mRNA
      of approximately 2.9 and 3.5 kb were detected in the duodenum, jejunum, and ileum
      of the small intestine and are presumed to result from alternative
      polyadenylation. Uptake of [(3)H]-Gly-Sar was measured in Chinese hamster ovary
      cells transiently transfected with a pPepT1 expression vector to study the
      functional expression of pPepT1. Peptide transport was H(+)-dependent, with an
      optimal pH of 6.0 to 6.5. The ability of pPepT1 to transport various peptides was
      assayed by calculating the concentration of unlabeled peptide that inhibited 50%
      of [(3)H]-Gly-Sar uptake (IC(50)) in transfected cells. Eleven dipeptides and two
      tripeptides had IC(50) values that ranged from 0.004 to 0.53 mM. Three peptides,
      Lys-Lys, Arg-Lys, and Lys-Trp-Lys, had IC(50) values greater than 1. 38 mM and
      seem to be poor substrates for pPepT1. For all three tetrapeptides examined,
      uptake of Gly-Sar was too small to measure, even at a concentration of 10 mM
      tetrapeptide; therefore, IC(50) values could not be calculated. These results
      demonstrate that pPepT1 can transport a variety of dipeptides and tripeptides but
      not tetrapeptides.

PMID- 15583058
TI  - The effect of a condensed tannin-containing forage on methane emission by goats.
AB  - The objective of this study was to compare methane emission by goats consuming
      the condensed tannin-containing forage sericea lespedeza (Les-pedeza cuneata) or
      a mixture of crabgrass (Digitaria ischaemum) and Kentucky 31 tall fescue (Festuca
      arundinacea). Two groups of 12 Angora does (initial average BW = 41.5 +/- 2.7 kg)
      that previously grazed a pasture of sericea lespedeza or crabgrass/tall fescue
      for approximately 4 mo were used. After 1 wk of adaptation to metabolism cages,
      gas exchange was measured for 24 h in an open-circuit respiration calorimetry
      system with four head boxes. Forage harvested daily from the previously grazed
      pastures was consumed ad libitum. Crude protein concentration was 10.3 and 13.0%,
      IVDMD was 64.5 and 75.3%, and the level of condensed tannins was 17.7 and 0.5%
      for sericea lespedeza and crabgrass/tall fescue, respectively. Dry matter intake
      (1.11 vs. 0.67 kg/d) and digestible DMI (estimated from IVDMD; 0.71 vs. 0.51
      kg/d) were greater (P < 0.01) for sericea lespedeza than for crabgrass/tall
      fescue. Ruminal ammonia N (3.7 and 9.9 mg/dL; P < 0.001) and plasma urea-N
      concentrations (16.7 and 20.9 mg/dL; P = 0.07) were lower for sericea lespedeza
      than for crabgrass/tall fescue. Concentrations of individual and total VFA and
      the acetate-to-propionate ratio in ruminal fluid did not differ between
      treatments (P > 0.19). Despite higher DMI by goats fed sericea lespedeza, daily
      energy expenditure (409 vs. 431 kJ/kg BW(0.75)), heart rate (70 vs. 73
      beats/min), and the ratio of energy expenditure to heart rate (5.82 vs. 5.94) did
      not differ between sericea lespedeza and crabgrass/tall fescue, respectively (P >
      0.13). Methane emission expressed as both quantity per day or relative to DMI was
      lower (P <0.001) for sericea lespedeza than for crabgrass/tall fescue (7.4 vs.
      10.6 g/d and 6.9 vs. 16.2 g/kg DMI). Substantial differences between the forages
      in condensed tannins concentration and methane emission by Angora goats suggest
      that condensed tannins decreased methane emission.

PMID- 15583059
TI  - Efficacy of using a combination of rendered protein products as an undegradable
      intake protein supplement for lactating, winter-calving, beef cows fed bromegrass
      hay.
AB  - Seventy-two (36 in each of two consecutive years) lactating, British-crossbred
      cows (609 +/- 19 kg) were used to evaluate effects of feeding a feather meal
      blood meal combination on performance by beef cows fed grass hay. Bromegrass hay
      (9.6% CP, DM basis) was offered ad libitum and intake was measured daily in
      individual Calan electronic headgates. Acclimation to Calan gates began
      approximately 20 d after parturition, and treatments were initiated 21 d later.
      Cows were assigned randomly to one of four treatments (DM basis) for 60 d: 1)
      nonsupplemented control (CON), 2) energy control (ENG; 790 g/d; 100% beet pulp),
      3) degradable intake protein (DIP; 870 g/d; 22% beet pulp and 78% sunflower
      meal), or 4) undegradable intake protein (UIP; 800 g/d; 62.5% sunflower meal, 30%
      hydrolyzed feather meal, and 7.5% blood meal). Net energy concentrations of
      supplements were formulated to provide similar NE(m) intakes (1.36 Mcal/d). The
      DIP and UIP supplements were calculated to supply similar amounts of DIP (168
      g/d) and to supply 64 and 224 g/d of UIP, respectively. Forage DMI (kg/d)
      decreased in supplemented vs. nonsupplemented (P = 0.03) and DIP vs. UIP (P =
      0.001); however, when expressed as a percentage of BW, forage DMI was not
      different (P = 0.23). Supplemented cows tended (P = 0.17) to lose less BW than
      CON. Body condition change was not affected (P = 0.60) by postpartum
      supplementation. No differences were noted in milk production (P = 0.29) or in
      calf gain during the supplementation period (P = 0.74). Circulating insulin
      concentrations were not affected by treatment (P = 0.42). In addition,
      supplementation did not affect circulating concentrations of NEFA (P = 0.18) or
      plasma urea nitrogen (P = 0.38). Results of the current study indicate that
      supplementation had little effect on BW, BCS, milk production, or calf BW when a
      moderate-quality forage (9.6% CP) was fed to postpartum, winter-calving cows in
      optimal body condition (BCS > 5). Supplemental UIP did not enhance cow
      performance during lactation. Forage UIP and microbial protein supply were
      adequate to meet the metabolizable protein requirements of lactating beef cows
      under the conditions of this study.

PMID- 15583060
TI  - Characterization of biological types of cattle (Cycle VII): Carcass, yield, and
      longissimus palatability traits.
AB  - The objective of this experiment was to provide a current evaluation of the seven
      most prominent beef breeds in the United States and to determine the relative
      changes that have occurred in these breeds since they were evaluated with samples
      of sires born 25 to 30 yr earlier. Carcass (n = 649), yield (n = 569), and
      longissimus thoracis palatability (n = 569) traits from F(1) steers obtained from
      mating Hereford, Angus, and MARC III cows to Hereford (H), Angus (A), Red Angus
      (RA), Charolais (C), Limousin (L), Simmental (S), or Gelbvieh (G) sires were
      compared. Data were adjusted to constant age (445 d), carcass weight (363 kg),
      fat thickness (1.1 cm), fat trim percent (25%), and marbling (Small(35))
      endpoints. For Warner-Bratzler shear force and trained sensory panel traits, data
      were obtained on LM from steaks stored at 2 degrees C for 14 d postmortem. The
      following comparisons were from the age-constant endpoint. Carcasses from L-, G-,
      and H-sired steers (361, 363, and 364 kg, respectively) were lighter (P < 0.05)
      than carcasses from steers from all other sire breeds. Adjusted fat thickness for
      carcasses from A-, RA-, and H-sired steers (1.5, 1.4, and 1.3 cm, respectively)
      was higher (P < 0.05) than for carcasses from steers from all other sire breeds
      (0.9 cm). Longissimus muscle areas were largest (P < 0.05) for carcasses from L-,
      C-, S-, and G-sired steers (89.9, 88.7, 87.6, and 86.5 cm(2), respectively) and
      smallest for carcasses from H- and RA-sired steers (79.5 and 78.4 cm(2)). A
      greater (P < 0.05) percentage of carcasses from RA- and A-sired steers graded
      USDA Choice (90 and 88%, respectively) than from carcasses from other sire breeds
      (57 to 66%). Carcass yield of boneless, totally trimmed retail product was least
      (P < 0.05) for RA- and A-sired steers (59.1 and 59.2%, respectively) and greatest
      (P < 0.05) for G, L-, C-, and S-sired steers (63.0 to 63.8%). Longissimus muscle
      from carcasses of A-sired steers (4.0 kg) had lower (P < 0.05) Warner-Bratzler
      shear force values than LM from carcasses of G- and C-sired steers (4.5 to 4.3
      kg, respectively). Trained sensory panel tenderness and beef flavor intensity
      ratings for LM did not differ (P < 0.05) among the sire breeds. Continental
      European breeds (C, L, S, and G) were still leaner, more heavily muscled, and had
      higher-yielding carcasses than did British breeds (H, A, and RA), with less
      marbling than A or RA, although British breeds have caught up in growth rate.

PMID- 15583061
TI  - Hepatic corticosteroid-binding globulin (CBG) messenger RNA expression and plasma
      CBG concentrations in young pigs in response to heat and social stress.
AB  - Plasma cortisol, porcine corticosteroid-binding globulin (pCBG), hepatic CBG
      expression, and other physiological and behavioral measures of stress were
      studied in pigs in response to elevated temperature in conjunction with
      establishing a social hierarchy. Twenty-four crossbred pigs were weaned at 25 d
      of age (three or six pigs from six sows) and housed in littermate groups at 23 +/
      2 degrees C. At 57 d of age (d 0), animals were weighed and placed under general
      anesthesia for collection of blood (10 mL) and liver (approximately 100 mg)
      samples. On d 1, three unacquainted pigs of similar BW (23 +/- 1 kg) from
      different litters were allotted to each of eight nursery pens within two
      environmentally controlled rooms (12 pigs per room). From d 1 to 7, one room was
      maintained at 23 +/- 2 degrees C (CON) and the other at 33 +/- 2 degrees C
      (HEAT). Both rooms were kept at 23 +/- 2 degrees C from d 8 to 14. Animals were
      videotaped for 72 h beginning on d 1 and 8 to document behavioral changes in
      response to room temperature. The social hierarchy of pigs within each pen was
      based on fight activity recorded on d 1 to 3. Blood and liver tissue were
      collected again on d 7 and 14. The ADG for HEAT pigs increased (P < 0.05) over d
      8 to 14 compared with d 1 to 7. In contrast to CON pigs, HEAT pigs displayed
      increased (P < 0.01) drinking but decreased feeding and lying in contact with
      other pigs from d 1 to 3, and similar drinking and feeding but increased (P <
      0.01) lying with contact behaviors from d 8 to 10. With the exception of
      subordinate pigs exhibiting less (P < 0.05) frequent standing/walking behavior
      than the dominant or intermediate pigs on d 1 to 3, frequency of behaviors for
      both recorded time periods did not differ among pigs due to social status,
      regardless of treatment. The concentration of plasma haptoglobin in HEAT pigs on
      d 7 compared with d 0 increased (467 vs. 763 mg/L; P < 0.05), whereas cortisol
      and pCBG decreased (274 vs. 235 nmol/L and 11.4 vs. 9.9 mg/L, respectively; P <
      0.05) as a result of treatment. The free cortisol index (total cortisol/pCBG) was
      greater (P < 0.05) in HEAT pigs on d 14 than on d 0 or 7. Hepatic CBG mRNA level
      was not affected by treatment. On d 14, HEAT pigs had plasma cortisol, pCBG, and
      haptoglobin concentrations similar to those of CON pigs. These results indicate
      that measured behavioral and physiological responses were not related to social
      status, and decreased circulating levels of cortisol and pCBG in pigs following a
      7-d exposure to elevated temperature may not be determined by hepatic CBG mRNA
      expression.

PMID- 15583062
TI  - Effects of castration, tooth resection, or tail docking on plasma metabolites and
      stress hormones in young pigs.
AB  - Changes in the activity of the sympathetic nervous system or in the hypothalamo
      pituitary-adrenal axis have been extensively used to evaluate pain induced by
      castration or tail docking in numerous species. Such data are missing in pigs.
      Therefore, three experiments were conducted to determine the effects of
      castration, tail docking, or tooth resection on stress hormones. Glucose and
      lactate also were measured because catecholamines stimulate mobilization of
      glycogen, which results in glucose and lactate release. In Exp.1, 18 male pigs
      from seven litters (two or three pigs per litter) were catheterized surgically
      into one jugular vein, under general anesthesia, at 5 or 6 d of age. Two days
      later, they were submitted either to bilateral castration, control handling, or
      no handling (n = 6 per group). Blood samples were collected before (- 15 and -2
      min) and after (5, 15, 30, 60, 90, 180 min) the experimental treatment. In Exp.
      2, 27 female pigs from 12 litters (one to four pigs per litter) were submitted
      either to tooth clipping with pliers, tooth resection with a grinder apparatus,
      control handling, or no handling (n = 6 or 7 per group) at 1 d of age. In Exp. 3,
      17 female pigs from nine litters (one to three pigs per litter) were submitted to
      one of the following treatments: 1) tail docking with an electric-heated scissor
      docking iron, 2) control handling, and 3) no handling (n = 5 or 6 per group) at 1
      d of age. Castration induced significant (P < 0.05) increases in
      adrenocorticotropin hormone (ACTH; from 5 to 60 min), cortisol (from 15 to 90
      min), and lactate (from 5 to 30 min). These variations are indicative of stress
      and tissue damage following castration. In contrast, neither tail docking nor
      tooth resection had marked effects on plasma cortisol, ACTH, glucose, and
      lactate. Measurements of plasma cortisol, lactate, and ACTH could be useful for
      validating treatments designed to relieve the distress reaction induced by
      castration in pigs.

PMID- 15583063
TI  - Effects of different cereal grains and ractopamine hydrochloride on performance,
      carcass characteristics, and fat quality in late-finishing pigs.
AB  - Forty-eight barrows and forty-eight gilts (PIC 337 sires x PIC C22 dams) were
      evaluated to determine the effects of feeding ractopamine hydrochloride (RAC) and
      different cereal grains on the carcass and fat quality in late finishing pigs.
      The study was carried out using four replicates with 24 animals in each replicate
      (four pigs per pen, six pens per replicate, two replicates per slaughter date, 12
      pens per slaughter date). Treatments for the experiment included corn, wheat, and
      barley (early finisher period); and corn, corn + RAC, wheat, wheat + RAC, barley,
      and barley + RAC for the late finisher period. Ractopamine was fed at the level
      of 10 mg/kg (as-fed basis) of feed. Pigs were allotted to early finisher period
      treatments at approximately 45 kg BW. Pigs were then given late finisher period
      treatments at approximately 80 kg BW and fed for 28 d. The dietary digestible
      lysine level for all diets was maintained at 2.7 g/Mcal of ME. Pigs fed the wheat
      and corn diets during the late finisher period had a greater (P <0.05) G:F than
      those fed the barley diets. Pigs fed diets with RAC had lower (P <0.05) leaf fat
      weights, 10th-rib fat, last-rib fat, and belly firmness and had improved (P
      <0.05) dressing percents and loin muscle areas compared with those not receiving
      RAC. Pigs fed the wheat diets had a greater (P <0.05) dressing percent than those
      receiving the barley diets, but pigs fed the barley diets had a higher (P <0.05)
      Minolta L* for fat color than pigs fed wheat. Pigs fed diets containing RAC
      produced pork that was less tender (P <0.05) compared with pigs that did not
      receive RAC. Linoleic acid percent values were higher (P <0.05) for pigs fed
      diets with RAC than in those that did not. Feeding RAC improved G:F and lowered
      feed intake of pigs during the late finisher period (P <0.05). Feeding diets
      equal in lysine (2.7 g/Mcal of ME) but varying in ME, whether based on corn,
      wheat, or barley with or without RAC, had little to no effect on carcass, meat,
      or fat quality attributes.

PMID- 15583064
TI  - A beef herd model for simulating feed intake, animal performance, and manure
      excretion in farm systems.
AB  - A beef herd submodel was created for integration with other farm components to
      form a whole-farm model capable of simulating a wide range of beef production
      systems. This herd submodel determined the best available feed or feed mix to
      meet the fiber, energy, and protein requirements for each of up to six animal
      groups on the farm. The groups comprised any combination of cows, nursing calves,
      young heifers, yearling heifers, stockers, and finishing cattle. Protein, energy,
      and mineral requirements were determined for each group using the Cornell Net
      Carbohydrate and Protein System, Level 1. Diets were formulated to meet these
      requirements with available feeds, and the resulting feed intake, growth, and
      manure DM and nutrient (N, P, and K) excretions were predicted. Required feed
      characteristics included CP, ruminally degradable protein, acid detergent
      insoluble protein, NDF, P, and K concentrations. Feed intake was predicted by
      considering energy intake, potentially limited by fill, and exceeding a minimum
      roughage requirement. Fill and roughage limits were functions of feed NDF
      concentrations adjusted to consider particle size distribution and the relative
      rate of ruminal digestibility or the physical effectiveness of the fiber. The
      herd submodel was verified to predict feed intakes, nutrient requirements, diets,
      and manure excretions similar to those recommended or measured for beef animals.
      Incorporation of the beef herd submodel with other farm components, including
      crop growth (alfalfa, grass, corn, small grain, and soybean), harvest, storage,
      feeding, grazing, and manure handling, provided the Integrated Farm System Model.
      This comprehensive farm-simulation model is a useful research and teaching tool
      for evaluating and comparing the long-term performance, economics, and
      environmental impact of beef, dairy, and crop production systems.

PMID- 15583065
TI  - Diet modifications to improve finishing pig growth performance and pork quality
      attributes during periods of heat stress.
AB  - A total of 196 barrows (88 kg) were used in a 2 x 2 factorial arrangement of
      treatments and housed in a facility (seven pigs per pen) where temperatures
      cycled between 27 and 35 degrees C. Treatments consisted of (as-fed basis) two CP
      levels (13.6 or 11.3%) and two levels of added fat (1 or 8%). Diets were
      formulated to the same true digestible lysine:ME ratio (1.68 g of lysine/Mcal of
      ME). Diets were fed and growth variables were measured until pigs reached 114 kg
      of BW. Ham and LM (loin) 24-h pH (PH24), and light reflectance (CIE L*, and a*,
      and b*, and hue angle) were taken after slaughter. Additionally, loins were
      removed and measured for i.m. fat, moisture, glycolytic potential, and subjected
      to a 7-d retail display evaluation that measured pH, light reflectance, and
      subjective color and odor score. The remaining boneless lumbar loin segment was
      vacuum-sealed for 14 d and subsequently measured for pH, light reflectance, and
      color. Pigs fed the high-CP, low-fat diet had a lower ADG than all other
      treatments (P = 0.06). High-fat feeding resulted in improved ADG (CP x Fat; P =
      0.06) and G:F (Fat effect; P < 0.01). Higher fat and lower protein levels both
      increased final BF (P = 0.07). Pigs fed the low-CP diets had lower ham PH24 (P <
      0.01). Loin PH24 was higher with high fat feeding (P = 0.10). Additionally, pigs
      fed high fat diets had lower L* values on the ham face and cut loin 24 h after
      slaughter (Fat effect; P <or= 0.02). These loin color differences were maintained
      through the 7-d retail display and 14-d storage period. There were no differences
      in loin i.m. fat or moisture content; however, high-fat feeding tended to
      decrease loin glycolytic potential (P = 0.11). These results suggest that in a
      hot environment, decreased CP content improved finishing pig ADG when dietary fat
      supplementation was low. High dietary fat inclusion during heat stress improved
      ADG and G:F, especially when CP level was elevated. High-fat diets fed in a hot
      environment increased pork color intensity by decreasing the glycolytic potential
      at slaughter and elevating muscle pH.

PMID- 15583066
TI  - Effect of sow parity and weight at service on target maternal weight and energy
      for gain in gestation.
AB  - The objective of this study was to evaluate targeted maternal weight gains in
      sows by parity group during gestation. Weight and backfat gains during gestation
      by parity, weight, and backfat groups also were analyzed. The data evaluated were
      a subset (374 sows) of a larger experiment that compared three methods of feeding
      sows during gestation on weight and backfat gains and subsequent reproductive
      performance. Feed allowances were based on modeled calculations of energy and
      nutrient requirements to achieve target sow maternal weight and backfat gains.
      Actual backfat gain for gilts and sows was regressed on maternal weight gain and
      estimated energy available for gain. The regression equations were then used to
      predict maternal weight gains for target backfat gains for three parity groups
      (gilts, Parity 1 and 2 sows, and Parity 3 and older sows). For gilts and Parity 1
      and 2 sows, much greater target maternal weight gains are required to achieve 6
      and 9 mm of backfat gain, whereas Parity 3 and older sows require maternal weight
      gains similar to those targeted to achieve the desired backfat gain. Given
      similar energy intake levels above maintenance, gilts gained more weight than
      multiparous sows, as gain was based more on protein and less on fat and thus was
      more efficient. Gilts required more maternal weight gain than sows to achieve
      similar backfat gains due to the higher protein and low fat contents of gain in
      younger, lighter sows compared with older parity sows. Low-backfat sows that
      needed to gain large amounts of backfat failed to achieve these large gains. We
      speculate this failure may be due to lower tissue insulation levels with the low
      backfat levels and higher activity levels of these sows compared with high
      backfat sows. It seems that both parity and weight are individually important
      factors that influence energy and nutrient requirements for gestation in the
      modern sow.

PMID- 15583067
TI  - Dry matter intake and digestion of alfalfa harvested at sunset and sunrise.
AB  - The preference exhibited by animals in selecting one feed over another is
      important only if the preferred diet is consumed daily in larger quantities,
      digested to a greater extent, or both. Six alfalfa (Medicago sativa L.) hays were
      harvested in pairs at sunset (PM) and sunrise (AM) on consecutive days at three
      harvest dates. A previous study of these hays demonstrated differences in
      ruminant preference favoring PM harvests. This study evaluated the effects of
      time of cutting and harvest date on voluntary DMI and nutrient digestibility. The
      hays were field-cured, baled, and chopped before evaluation for intake and
      digestibility. Studies were conducted for sheep (Ovis aries), goats (Capra
      hircus), and cattle (Bos taurus). Goats, but not steers or sheep, demonstrated
      differences in nutrient digestibility between PM- and AM-cut hays. Goats consumed
      more PM than AM hay (2.97 vs. 2.83 kg/100 kg of BW; P = 0.07) and digested it to
      a greater extent (0.710 vs. 0.696; P = 0.03), resulting in greater digestible DMI
      (2.11 vs. 1.97 kg/100 kg of BW; P = 0.03). Sheep consumed (mean = 2.52 kg/100 kg
      of BW; P = 0.59) and digested (mean = 0.681; P = 0.25) PM- and AM-cut hays
      similarly. Steers consumed larger quantities of PM-than AM-cut hay (2.90 vs. 2.62
      kg/100 kg of BW; P = 0.11), but digestion did not differ with cutting time (mean
      = 0.660; P = 0.75). Difference values (composition of fed hay minus composition
      of orts) indicated that sheep and goats selected from the feed offered similarly,
      whereas steers selected differently. Difference values for CP averaged 94 and 101
      g/kg for goats and sheep and 32 g/kg for steers (P < 0.01), and difference values
      for NDF averaged 185 and 196 g/kg for goats and sheep and 73 g/kg for steers (P
      <or= 0.01). Steer DMI and digestible DMI were associated with preference (r =
      +0.83, P <or= 0.05; and r = +0.89, P <or= 0.05) and with coordinates for
      preference criteria (dimension 1; r = +0.90, P <or= 0.05; and r = +0.89, P <or=
      0.05) from a previous preference trial. Intake and digestion responses for goats
      and sheep showed no relationship with the previous preference trial measurements.
      For cattle and goats, the management strategy of mowing in the afternoon seems to
      take advantage of small, but influential diurnal changes in the soluble
      carbohydrate fraction and offers the potential to improve forage quality.

PMID- 15583069
TI  - Angiotensin II-mediated vascular inflammation: the balance between vascular
      endothelial growth factor and angiopoietins.

PMID- 15583070
TI  - Sex steroids, cardiovascular disease, and hypertension: unanswered questions and
      some speculations.

PMID- 15583072
TI  - Critical value of the electrocardiogram in LVH: from predictive index to
      therapeutic reassessment.

PMID- 15583073
TI  - White-coat hypertension and risk of stroke: do the data really tell us what we
      need to know?

PMID- 15583074
TI  - Comparing the roles of physical activity and fitness in arterial stiffness: how
      important is exposure measurement error?

PMID- 15583075
TI  - Obesity-associated hypertension: new insights into mechanisms.
AB  - Obesity is strongly associated with hypertension and cardiovascular disease.
      Several central and peripheral abnormalities that can explain the development or
      maintenance of high arterial pressure in obesity have been identified. These
      include activation of the sympathetic nervous system and the renin-angiotensin
      aldosterone system. Obesity is also associated with endothelial dysfunction and
      renal functional abnormalities that may play a role in the development of
      hypertension. The continuing discovery of mechanisms regulating appetite and
      metabolism is likely to lead to new therapies for obesity-induced hypertension.
      Better understanding of leptin signaling in the hypothalamus and the mechanisms
      of leptin resistance should facilitate therapeutic approaches to reverse the
      phenomenon of selective leptin resistance. Other hunger and satiety signals such
      as ghrelin and peptide YY are potentially attractive therapeutic strategies for
      treatment of obesity and its complications. These recent discoveries should lead
      to novel strategies for treatment of obesity and hypertension.

PMID- 15583076
TI  - Stroke reduction in hypertensive adults with cardiac hypertrophy randomized to
      losartan versus atenolol: the Losartan Intervention For Endpoint reduction in
      hypertension study.
AB  - The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study
      showed that treatment with the angiotensin II type-1 receptor antagonist losartan
      reduces overall stroke risk compared with conventional therapy with the beta
      blocker atenolol. We conducted secondary analyses in LIFE to determine the extent
      to which the cerebrovascular benefits of losartan apply to different clinical
      subgroups and stroke subtypes and to assess the dependence of these benefits on
      baseline and time-varying covariates. Among 9193 hypertensive patients with
      electrocardiographic evidence of left ventricular hypertrophy, random allocation
      to losartan-based treatment lowered the risk of fatal (hazard ratio [HR], 0.65;
      95% confidence interval [CI], 0.43 to 0.96; P=0.032) and atherothrombotic stroke
      (HR, 0.72; 95% CI, 0.59 to 0.88; P=0.001) compared with atenolol-based therapy.
      Although comparable risk reductions occurred for hemorrhagic and embolic stroke,
      these were not statistically significant. The number of neurological deficits per
      stroke was similar, but there were fewer strokes in the losartan group for nearly
      every level of stroke severity. Effects were consistent in all clinical subgroups
      except for those defined by age and ethnicity. The benefits of losartan on all
      strokes were independent of baseline and time-varying risk factors, including
      blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54
      for the average participant, declining to 25, 24, and 9 for patients with
      cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation,
      respectively. In conclusion, substantial cerebrovascular benefit could be
      realized with the institution of losartan-based therapy over conventional therapy
      among hypertensive patients with left ventricular hypertrophy across the spectrum
      of cardiovascular risk.

PMID- 15583077
TI  - Selective angiotensin-converting enzyme C-domain inhibition is sufficient to
      prevent angiotensin I-induced vasoconstriction.
AB  - Somatic angiotensin-converting enzyme (ACE) contains 2 domains (C-domain and N
      domain) capable of hydrolyzing angiotensin I (Ang I) and bradykinin. Here we
      investigated the effect of the selective C-domain and N-domain inhibitors RXPA380
      and RXP407 on Ang I-induced vasoconstriction of porcine femoral arteries (PFAs)
      and bradykinin-induced vasodilation of preconstricted porcine coronary
      microarteries (PCMAs). Ang I concentration-dependently constricted PFAs. RXPA380,
      at concentrations >1 mumol/L, shifted the Ang I concentration-response curve
      (CRC) 10-fold to the right. This was comparable to the maximal shift observed
      with the ACE inhibitors (ACEi) quinaprilat and captopril. RXP407 did not affect
      Ang I at concentrations < or =0.1 mmol/L. Bradykinin concentration-dependently
      relaxed PCMAs. RXPA380 (10 micromol/L) and RXP407 (0.1 mmol/L) potentiated
      bradykinin, both inducing a leftward shift of the bradykinin CRC that equaled
      approximately 50% of the maximal shift observed with quinaprilat. Ang I added to
      blood plasma disappeared with a half life (t(1/2)) of 42+/-3 minutes. Quinaprilat
      increased the t(1/2) approximately 4-fold, indicating that 71+/-6% of Ang I
      metabolism was attributable to ACE. RXPA380 (10 micromol/L) and RXP407 (0.1
      mmol/L) increased the t(1/2) approximately 2-fold, thereby suggesting that both
      domains contribute to conversion in plasma. In conclusion, tissue Ang I-II
      conversion depends exclusively on the ACE C-domain, whereas both domains
      contribute to conversion by soluble ACE and to bradykinin degradation at tissue
      sites. Because tissue ACE (and not plasma ACE) determines the hypertensive
      effects of Ang I, these data not only explain why N-domain inhibition does not
      affect Ang I-induced vasoconstriction in vivo but also why ACEi exert blood
      pressure-independent effects at low (C-domain-blocking) doses.

PMID- 15583078
TI  - Calcitonin gene-related peptide protects against hypertension-induced heart and
      kidney damage.
AB  - Calcitonin gene-related peptide is a potent vasodilator neuropeptide that is
      localized in perivascular sensory nerves. To determine whether alpha-calcitonin
      gene-related peptide possesses protective activity against hypertension-induced
      end organ damage, hypertension was induced in alpha-calcitonin gene
      related/calcitonin peptide knockout and wild-type mice by uninephrectomy,
      deoxycorticosteroid administration, and 0.9% saline drinking water. These mice
      were instrumented previously for long-term telemetric blood pressure recording.
      Control groups were sham-operated and given tap water. Mean arterial pressures
      were determined, and 3 weeks after initiation of each protocol, tissues were
      taken for histopathologic studies. The deoxycorticosteroid-salt protocol produced
      a significant 35% mean arterial pressure increase in both mouse strains. No
      pathological changes were observed in sections of aortas and femoral arteries
      from any of the groups studied. Likewise, heart and kidney sections from the
      hypertensive wild-type mice showed no pathological changes compared with their
      normotensive counterparts. In contrast, marked vasculitis was seen in the heart
      sections from the deoxycorticosteroid-salt-treated alpha-calcitonin gene-related
      peptide knockout mice with thickening and inflammation of the vessel walls. In
      addition, myocarditis and focal epicarditis with areas of myocardial necrosis
      were present. Kidneys of these mice exhibited prominent glomerular changes
      including congestion of the capillary loops, focal mesangial and crescent
      proliferation, and focal histocytic infiltration. Urinary microalbumin was
      significantly higher in the hypertensive alpha-calcitonin gene-related peptide
      knockout compared with hypertensive wild-type mice. These data suggest that
      deletion of the alpha-calcitonin gene-related peptide gene makes the heart and
      kidneys more vulnerable to hypertension-induced end organ damage.

PMID- 15583079
TI  - Long-term clinical course of patients after termination of ventricular
      tachyarrhythmia by an implanted defibrillator.
AB  - BACKGROUND: The implanted cardioverter defibrillator (ICD) improves survival in
      high-risk cardiac patients. This analysis from the MADIT-II trial database
      examines the long-term clinical course and subsequent mortality risk of patients
      after termination of life-threatening ventricular tachyarrhythmias by an ICD.
      METHODS AND RESULTS: Life-table survival analysis was performed, and proportional
      hazards regression analysis was used to evaluate the contribution of baseline
      clinical factors and time-dependent defibrillator therapy to mortality during
      long-term follow-up. Of 720 patients with an ICD (average follow-up 21 months),
      169 patients received 701 antiarrhythmic device therapies for ventricular
      tachyarrhythmias. Few baseline characteristics distinguished patients who
      received appropriate ICD therapy for their first ventricular tachyarrhythmic
      episode. The probability of survival for at least 1 year after first therapy for
      ventricular tachycardia (VT) or ventricular fibrillation (VF) was 80%. The hazard
      ratios for the risk of death due to any cause in those who survived appropriate
      therapy for termination of VT and VF were 3.4 (P<0.001) and 3.3 (P=0.01),
      respectively, compared with those who survived without receiving ICD therapy,
      with a high frequency of heart failure and late nonsudden cardiac death after
      first successful ICD therapy for VF. CONCLUSIONS: Successful appropriate therapy
      by an ICD for VT or VF is associated with 80% survival at 1 year after arrhythmia
      termination. These patients are at increased risk for heart failure and nonsudden
      cardiac death after device termination of VT or VF and should receive special
      attention for the prevention and management of progressive left ventricular
      dysfunction during long-term follow-up.

PMID- 15583080
TI  - Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive
      left ventricular hypertrophy on the basis of strain rate imaging by tissue
      Doppler ultrasonography.
AB  - BACKGROUND: The differentiation of hypertrophic cardiomyopathy (HCM) from
      hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological
      information obtained by conventional echocardiography is occasionally
      problematic. We investigated whether strain rate (SR) imaging derived from tissue
      Doppler imaging (TDI) is able to discriminate HCM from H-LVH. METHODS AND
      RESULTS: Conventional echocardiography and TDI were performed with 34 patients
      with LVH and 16 reference subjects. Mean values of systolic strain
      (epsilon(sys)), peak systolic SR, and early diastolic SR obtained from 8 left
      ventricular (LV) segments were calculated. LV pressures were recorded
      simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH
      (n=14) on the basis of conventional echocardiography and endomyocardial biopsy
      findings. Multivariate analysis revealed that septum/posterior wall thickness
      ratio (P=0.00013) and epsilon(sys) (P<0.0001) were each able to discriminate HCM
      from H-LVH. A epsilon(sys) cutoff value of -10.6% discriminated between HCM and H
      LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy
      of 91.2%. The combination of the septum/posterior wall thickness ratio and
      epsilon(sys) discriminated HCM from H-LVH with a predictive accuracy of 96.1%.
      The epsilon(sys) parameter was significantly correlated with pulmonary arterial
      wedge pressure, LV end-diastolic pressure, the peak positive first derivative of
      LV pressure, and the time constant of LV pressure decay. CONCLUSIONS: SR imaging
      is able to discriminate HCM from H-LVH, with epsilon(sys) reflecting myocardial
      contractile and lusitropic properties.

PMID- 15583081
TI  - Detection of cardiac allograft rejection and response to immunosuppressive
      therapy with peripheral blood gene expression.
AB  - BACKGROUND: Assessment of gene expression in peripheral blood may provide a
      noninvasive screening test for allograft rejection. We hypothesized that changes
      in peripheral blood expression profiles would correlate with biopsy-proven
      rejection and would resolve after treatment of rejection episodes. METHODS AND
      RESULTS: We performed a case-control study nested within a cohort of 189 cardiac
      transplant patients who had blood samples obtained during endomyocardial biopsy
      (EMB). Using Affymetrix HU133A microarrays, we analyzed whole-blood expression
      profiles from 3 groups: (1) control samples with negative EMB (n=7); (2) samples
      obtained during rejection (at least International Society for Heart and Lung
      Transplantation grade 3A; n=7); and (3) samples obtained after rejection, after
      treatment and normalization of the EMB (n=7). We identified 91 transcripts
      differentially expressed in rejection compared with control (false discovery rate
      <0.10). In postrejection samples, 98% of transcripts returned toward control
      levels, displaying an intermediate expression profile for patients with treated
      rejection (P<0.0001). Cluster analysis of the 40 transcripts with >25% change in
      expression levels during rejection demonstrated good discrimination between
      control and rejection samples and verified the intermediate expression profile of
      postrejection samples. Quantitative real-time polymerase chain reaction confirmed
      significant differential expression for the predictive markers CFLAR and SOD2
      (UniGene ID No. 355724 and No. 384944). CONCLUSIONS: These data demonstrate that
      peripheral blood expression profiles correlate with biopsy-proven allograft
      rejection. Intermediate expression profiles of treated rejection suggest
      persistent immune activation despite normalization of the EMB. If validated in
      larger studies, expression profiling may prove to be a more sensitive screening
      test for allograft rejection than EMB.

PMID- 15583082
TI  - Anti-transforming growth factor antibody at low but not high doses limits
      cyclosporine-mediated nephrotoxicity without altering rat cardiac allograft
      survival: potential of therapeutic applications.
AB  - BACKGROUND: Long-term treatment of cardiac transplant recipients with
      cyclosporine results in a progressive decline in kidney function in a large
      number of patients. This complication is one of the most important prognostic
      parameters that determine the outcome of cardiac transplantation. Transforming
      growth factor-beta (TGF-beta) is one of the most potent mediators of the
      fibrogenic effects of cyclosporine. METHODS AND RESULTS: With the use of an
      experimental rodent model, heterotopic heart transplantation was performed,
      creating histocompatibility-disparate allografts. Because TGF-beta in part
      mediates both the immunosuppressive and nephrotoxic effects of cyclosporine,
      recipients were treated with cyclosporine with and without anti-TGF-beta antibody
      to determine whether anti-TGF-beta antibody could reduce the nephrotoxic effects
      of cyclosporine. Intrarenal expression of TGF-beta, collagen, fibronectin, matrix
      metalloproteinase-2, and tissue inhibitor of metalloproteinase-2 was studied with
      the use of reverse transcription-polymerase chain reaction. Intrarenal expression
      of TGF-beta protein was studied by immunohistochemistry and with the use of ELISA
      to quantify circulating levels of TGF-beta protein in plasma. Cyclosporine
      induced graft survival (immunosuppressive effect) was abrogated with a higher
      concentration (2.5 mg/kg) of anti-TGF-beta antibody, whereas a lower
      concentration (1 mg/kg) inhibited both cyclosporine-induced expression of
      fibrogenic molecules and renal toxicity. CONCLUSIONS: These results provide
      credence to the pivotal role of TGF-beta in immunosuppression-associated renal
      toxicity in recipients of cardiac transplantation. Furthermore, these findings
      support a potentially significant therapeutic use of optimal concentration of
      anti-TGF-beta antibody to ameliorate cyclosporine-associated nephrotoxicity in
      cardiac transplant recipients.

PMID- 15583083
TI  - Detrimental ventricular remodeling in patients with congenital complete heart
      block and chronic right ventricular apical pacing.
AB  - BACKGROUND: Although dual-chamber pacing improves cardiac function in patients
      with complete congenital atrioventricular block (CCAVB) by restoring
      physiological heart rate and atrioventricular synchronization, the long-term
      detrimental effect of asynchronous electromechanical activation induced by apical
      right ventricular pacing (RVP) has not been well clarified. METHODS AND RESULTS:
      Twenty-three CCAVB adults (24+/-3 years) with a DDD transvenous pacemaker
      underwent conventional echocardiography before implantation and, after at least 5
      years of RVP, an exercise test and echocardiography coupled with tissue Doppler
      imaging and tissue tracking. They were compared with 30 matched healthy control
      subjects. After 10+/-3 years of RVP, CCAVB adults had significantly higher values
      versus controls in terms of intra-left ventricular (LV) asynchrony (respectively,
      59+/-18 versus 19+/-9 ms, P<0.001), extent of LV myocardium displaying delayed
      longitudinal contraction (39+/-15% versus 10+/-7%, P<0.01), and septal-to
      posterior wall-motion delay (84+/-26 versus 18+/-9 ms, P<0.01). The ratio of late
      activated posterior to early-activated septal wall thickness was higher after
      long-term RVP than before (1.3+/-0.2 vs 1+/-0.1, P=0.05) and was higher than in
      controls (1+/-0.1, P<0.05). The percentage of patients with increased LV end
      diastolic diameter was higher after long-term RVP than before implantation and
      was higher than in controls (57% versus 13%, P<0.05, and 57% versus 0%, P<0.01,
      respectively). CCAVB patients with long-term RVP had a lower cardiac output than
      controls (3.8+/-0.6 versus 4.9+/-0.8 L/min, P<0.05) and lower exercise
      performance (123+/-24 versus 185+/-39 W, P<0.001). CONCLUSIONS: Prolonged
      ventricular dyssynchrony induced by long-term endovenous RVP is associated with
      deleterious LV remodeling, LV dilatation, LV asymmetrical hypertrophy, and low
      exercise capacity. These new data highlight the importance of the ventricular
      activation sequence in all patients with chronic ventricular pacing.

PMID- 15583084
TI  - Clinical decision making for endovascular repair of abdominal aortic aneurysm.

PMID- 15583085
TI  - Images in cardiovascular medicine. Rare form of right ventricular outflow tract
      obstruction.

PMID- 15583086
TI  - Images in cardiovascular medicine. Endocardial implantation of a cardioverter
      defibrillator in a 13-month-old child affected by long-QT syndrome and
      syndactyly.

PMID- 15583087
TI  - Coronary calcium screening and the American Heart Association news embargo.

PMID- 15583088
TI  - Heart failure disease management programs: not a class effect.

PMID- 15583089
TI  - Atherosclerosis imaging and the future of lipid management.

PMID- 15583092
TI  - Second guessing the second opinion.

PMID- 15583090
TI  - Lessons learned from a clinical trial.

PMID- 15583093
TI  - Ensuring preparedness for potential poliomyelitis outbreaks: Recommendations for
      the US poliovirus vaccine stockpile from the National Vaccine Advisory Committee
      (NVAC) and the Advisory Committee on Immunization Practices (ACIP).
AB  - Paralytic poliomyelitis was once endemic in the United States; however, because
      of high vaccination levels, the last case of wild disease occurred in 1979.
      Although worldwide polio eradication may be achieved in the near future, the
      presence of undervaccinated children in urban areas and among groups who refuse
      vaccination creates an outbreak risk, should importation of wild virus occur. In
      1999, the Advisory Committee on Immunization Practices (ACIP) recommended that
      inactivated poliovirus vaccine (IPV) be used for routine immunization of the US
      population and that oral poliovirus vaccine (OPV) be reserved for "mass
      vaccination campaigns to control outbreaks of paralytic polio." Subsequently, the
      sole US manufacturer of OPV withdrew from the market. In 2003, a joint National
      Vaccine Advisory Committee (NVAC)/ACIP working group was charged with reporting
      to its parent bodies concerning the need for a poliovirus vaccine stockpile.
      Based on that working group's report, the NVAC and ACIP have concluded that
      stockpiles of both IPV and OPV should be maintained. In the event of an outbreak
      in which OPV continues not to be available, IPV should be used for control, and a
      stockpile of 8 million doses seems to be sufficient. Should IPV be manufactured
      only in combination with other vaccines, appropriate procurement actions should
      be taken to ensure that uncombined IPV continues to be stockpiled. Under
      circumstances of diminished population immunity, OPV may offer outbreak control
      advantages. The NVAC and ACIP recommend that the United States collaborate with
      international agencies to provide guaranteed and rapid access to at least 8
      million doses of trivalent OPV or 8 million doses of each of the 3 types of
      monovalent OPV. The regulatory and practical obstacles to implementation of this
      recommendation will require assertive facilitation at high levels of the federal
      government and careful planning at the state and local levels.

PMID- 15583094
TI  - Iron deficiency in children with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Iron deficiency causes abnormal dopaminergic neurotransmission and
      may contribute to the physiopathology of attention-deficit/hyperactivity disorder
      (ADHD). OBJECTIVE: To evaluate iron deficiency in children with ADHD vs iron
      deficiency in an age- and sex-matched control group. DESIGN: Controlled group
      comparison study. SETTING: Child and Adolescent Psychopathology Department in
      European Pediatric Hospital, Paris, France. PATIENTS: Fifty-three children with
      ADHD aged 4 to 14 years (mean +/- SD, 9.2 +/- 2.2 years) and 27 controls (mean +/
      SD, 9.5 +/- 2.8 years). MAIN OUTCOME MEASURES: Serum ferritin levels evaluating
      iron stores and Conners' Parent Rating Scale scores measuring severity of ADHD
      symptoms have been obtained. RESULTS: The mean serum ferritin levels were lower
      in the children with ADHD (mean +/- SD, 23 +/- 13 ng/mL) than in the controls
      (mean +/- SD, 44 +/- 22 ng/mL; P < .001). Serum ferritin levels were abnormal
      (<30 ng/mL) in 84% of children with ADHD and 18% of controls (P < .001). In
      addition, low serum ferritin levels were correlated with more severe general ADHD
      symptoms measured with Conners' Parent Rating Scale (Pearson correlation
      coefficient, r = -0.34; P < .02) and greater cognitive deficits (r = -0.38; P <
      .01). CONCLUSIONS: These results suggest that low iron stores contribute to ADHD
      and that ADHD children may benefit from iron supplementation.

PMID- 15583095
TI  - Trends in state-specific prevalence of overweight and underweight in 2- through 4
      year-old children from low-income families from 1989 through 2000.
AB  - OBJECTIVES: To document overweight and underweight state-specific prevalence and
      examine trends among 2- through 4-year-old children from low-income families.
      METHODS: State-specific and overall overweight and underweight prevalence for
      1989, 1994, and 2000 and trend analyses during the study period are documented.
      Overweight was defined as a sex-specific body mass index (BMI) for age in the
      95th percentile or higher and underweight as a sex-specific BMI for age in less
      than the fifth percentile on the 2000 Centers for Disease Control and Prevention
      (CDC) growth charts. These analyses are based on one randomly selected record per
      child per year for 30 states consistently participating in the CDC Pediatric
      Nutrition Surveillance System in 1989, 1994, and 2000. Prevalence in 1989 and
      1994 is adjusted to state-specific age and race/ethnicity distribution of the
      population in 2000. Overweight and underweight prevalence were categorized as 5%
      or less, more than 5% to 10%, more than 10% to 15%, more than 15% to 20%, and
      more than 20%. RESULTS: The number of states that reported overweight prevalence
      of more than 10% increased from 11 in 1989 to 28 in 2000. Underweight decreased
      during the study period: 9 states in 1989 and 23 states in 2000 had a prevalence
      of 5% or less. No geographic predominance was apparent. Trend analyses showed
      significant increases in overweight in 30 states (P < .01) and decreases in
      underweight in 26 states (P < .05). CONCLUSIONS: Overweight is increasing and
      underweight is decreasing in our study population. We need to expand prevention
      and intervention efforts to reverse the rising trend of overweight in the United
      States.

PMID- 15583096
TI  - Relationships between maternal and child cardiovascular risk factors: ethnic
      differences and lack of influence of physical activity.
AB  - OBJECTIVES: To obtain information about the relationship between cardiovascular
      and diabetic risk factors of mothers and their children and to determine whether
      these relationships differ by physical activity or ethnicity. DESIGN: Prospective
      study. SETTING: The Texas site of the Studies of Child Activity and Nutrition
      Program. PATIENTS: A 1986 to 1989 triethnic sample (European American, African
      American, and Hispanic) of 133 mothers and their 6- to 7-year-old children. MAIN
      OUTCOME MEASURES: Maternal and child fasting insulin levels; total, high-density
      lipoprotein, and low-density lipoprotein cholesterol levels; triglyceride levels;
      waist circumference; systolic and diastolic blood pressures; height; weight; and
      body mass index. Maternal physical activity was assessed by means of a 7-day
      recall. Child physical activity was assessed by heart rate monitoring.
      Correlational methods were used to describe the relationships among metabolic
      risk factors and physical activity; chi2 tests of independence were used to
      examine the relationships between ethnic groups. RESULTS: Body mass index and
      waist circumference were significantly (P<.05) associated among Hispanic mothers
      and their children, but not in other ethnic groups. Insulin, high-density
      lipoprotein, and low-density lipoprotein levels were significantly associated
      among African American mothers and their children, but not in other ethnic
      groups. Maternal and child physical activity were not significantly associated
      with any of the risk variables or each other. CONCLUSION: The relationships
      between the risk factors of mothers and children differed by ethnicity, but not
      by physical activity.

PMID- 15583097
TI  - Rates and risk factors for sexual violence among an ethnically diverse sample of
      adolescents.
AB  - OBJECTIVES: To investigate the occurrence of rape/attempted rape and verbal
      sexual coercion among an ethnically diverse adolescent population and to evaluate
      whether unique risk factors existed for victims of either type of forced sexual
      experience. DESIGN: Cross-sectional survey assessing sexual violence within the
      past 12 months, behaviors that occurred on each subject's most recent date, and
      the occurrence of unwanted sexual experiences on any dates in the past year and
      details about that date. Subjects identified as experiencing either
      rape/attempted rape or verbal sexual coercion were compared with nonvictims using
      bivariate and multivariate analyses. SETTING: Urban adolescent health care
      facility. PARTICIPANTS: Female adolescents and young adults (n = 689) between the
      ages of 14 and 23 years who presented for care and met the eligibility criteria.
      RESULTS: Approximately 30% of young women reported having an unwanted sexual
      experience in the past year. The risk of rape/attempted rape was increased by
      past mild to moderate (adjusted odds ratio [AOR] = 4.27) or severe (AOR = 15.24)
      physical aggression by the dating partner; date-specific behaviors, including
      decreased level of romantic involvement (AOR = 0.63 per point decline) and going
      to the perpetrator's house to be alone (AOR = 3.01); past sexual victimization as
      an adolescent (AOR = 4.70); and lower levels of self-reported ethnic identity
      (AOR = 1.07 per point decline). More important, alcohol use by the victim or
      perpetrator was unrelated to an increased risk of rape/attempted rape. The risk
      of verbal sexual coercion was increased by past mild to moderate (AOR = 4.38) or
      severe (AOR = 13.79) verbal aggression from the dating partner; date-specific
      behaviors, including decreased level of romantic involvement (AOR = 0.70 per
      point decline) and greater number of past dates (AOR = 7.53); going to the
      perpetrator's house to be alone (AOR = 3.52); past sexual victimization as an
      adolescent (AOR = 9.83); pressures to use alcohol (AOR = 9.49); the victim not
      drinking alcohol during the date (AOR = 14.38); and increasing age discrepancy
      between victim and perpetrator (AOR = 1.23 per year increase). CONCLUSIONS:
      Approximately 1 in 4 urban young women reported having experienced verbal sexual
      coercion or rape/attempted rape by a date or acquaintance in the past year.
      Distinct risk profiles for rape/attempted rape and verbal sexual coercion were
      identified when compared with those who did not report any victimization.

PMID- 15583098
TI  - Projected economic costs due to health consequences of teenagers' loss of
      confidentiality in obtaining reproductive health care services in Texas.
AB  - BACKGROUND: We wanted to focus on the potential consequences of recently enacted
      legislation in Texas that limits adolescents' ability to obtain confidential
      reproductive health care services. OBJECTIVE: To assess the potential economic
      costs that result when adolescents do not seek reproductive health care services
      because their confidentiality is compromised. DESIGN: We developed a cost model
      to estimate the projected costs of parental consent and law enforcement reporting
      requirements based on data from the literature, the Texas Department of Health,
      and publicly funded family planning clinics in Texas. Univariate and multivariate
      sensitivity analyses explored different scenarios. SETTING: The state of Texas.
      PARTICIPANTS: Projected costs were estimated for all girls younger than 18 years
      using publicly funded reproductive health care services in Texas. MAIN OUTCOME
      MEASURES: We determined the projected number of additional pregnancies, births,
      abortions, and untreated sexually transmitted infections and resulting pelvic
      inflammatory disease and calculated the associated economic costs of these
      projected outcomes. RESULTS: The potential costs of parental consent and law
      enforcement reporting requirements in Texas were estimated at 43.6 million
      dollars (range, 11.8 million dollars to 56.6 million dollars) for girls younger
      than 18 years currently using publicly funded services. CONCLUSIONS: As
      policymakers throughout the United States search for ways to curtail adolescent
      sexual activity and its adverse consequences, this analysis suggests that the
      limiting of medical confidentiality and the resulting restricted use of
      reproductive health care services potentially have serious health and economic
      consequences.

PMID- 15583099
TI  - Mortality in childhood-onset epilepsy.
AB  - OBJECTIVES: To evaluate mortality in children with newly diagnosed epilepsy, to
      determine the risk of death, and to identify predictors of death from the point
      of diagnosis. DESIGN: Prospective community-based cohort of 613 children with
      newly diagnosed epilepsy. The outcome measure was death. Chi2 Tests were used for
      bivariate analyses and the Cox proportional hazards model for multivariable
      analyses. Standardized mortality ratios were used to quantify the excess
      mortality in the cohort relative to the population. RESULTS: Thirteen deaths
      occurred during 4733 person-years of follow-up, for a crude death rate of 2.7 per
      1000 person-years (0.52 per 1000 person-years in those with nonsymptomatic
      epilepsy and 12.6 per 1000 person-years in those with symptomatic epilepsy). Ten
      deaths were associated with the underlying cause of the seizures, 2 were
      associated with the occurrence or probable occurrence of seizures, and 1 was
      unrelated to seizures or the underlying disorder. On multivariable analysis,
      symptomatic etiology (rate ratio, 10.2; 95% confidence interval [CI], 2.1-49.6)
      and epileptic encephalopathy (rate ratio, 13.3; 95% CI, 3.4-51.7) were
      independently associated with mortality. The overall standardized mortality ratio
      for the cohort was 7.54 (95% CI, 4.38-12.99). In children with symptomatic
      epilepsy, the standardized mortality ratio was 33.46 (95% CI, 18.53-60.43), and
      in those with nonsymptomatic epilepsy, it was 1.43 (95% CI, 0.36-5.73).
      CONCLUSIONS: Children with epilepsy have an increased risk of death. Most deaths
      occur in children with severe underlying conditions and are not directly related
      to the occurrence of seizures.

PMID- 15583100
TI  - Visiting less than every day: a marker for later behavioral problems in Finnish
      preterm infants.
AB  - OBJECTIVE: To investigate the effect of parental visits during neonatal intensive
      care on the behavioral and emotional development of the child at school age.
      DESIGN: All premature infants born in Tampere University Hospital in Tampere,
      Finland, in 1989 who were admitted to the neonatal intensive care unit and who
      lived in the Tampere region (N = 67; 31 boys and 36 girls) formed the study
      group. Data on parental visits were collected from the hospital records. Child
      behavior was evaluated according to the Achenbach Child Behavior Checklist at the
      age of 7 to 8 years. A total of 48 (72%) of the mothers returned the
      questionnaires. RESULTS: The median number of visiting days per week was 6.2 for
      the mothers and 4.7 for the fathers. The children whose mothers visited daily had
      fewer behavioral and emotional problems at school age than those who had had
      fewer visits from their mothers (P = .04). The visiting frequency of the fathers
      was not significantly associated with later behavioral and emotional problems of
      the child. In this study, infrequent visits by the mother were a stronger risk
      factor for later psychological development than the medical risks of the preterm
      infant. CONCLUSIONS: Infrequent visits by mothers to the neonatal intensive care
      unit seem to be a marker for their children's later behavioral and emotional
      problems. This emphasizes the significance of early parent-infant contact and the
      vulnerability in early interaction. Less frequent visits may also indicate
      factors influencing the parent-child relationship in a way that leads to
      subsequent behavioral problems.

PMID- 15583101
TI  - Too many, too few, too concentrated? A review of the pediatric subspecialty
      workforce literature.
AB  - OBJECTIVES: To summarize recent pediatric subspecialty workforce analyses and to
      highlight similarities and differences across studies. DESIGN: By using MEDLINE,
      we conducted a systematic search of the literature published from January 1,
      1992, through December 31, 2002. We included research articles and task force
      reports, and abstracted author, year of publication, specialty, sample size,
      analytic perspective (eg, physician or academic department), inclusion of data on
      nonclinical activities, inclusion of an objective measure of demand, and
      workforce-related conclusions. RESULTS: We identified 41 relevant articles.
      Physician surveys provided data for most (n = 24) of these studies. Only 8
      studies attempted to make future workforce projections; of these 8 studies, 1
      explicitly accounted for nonclinical activities in its projections. An additional
      16 studies presented data on involvement in nonclinical activities. While some
      studies suggest that additional pediatric subspecialists are not needed, these
      studies did not include objective assessments of demand in geographic areas where
      pediatric subspecialty physicians are not available. Of those studies that took a
      market perspective and attempted to account for demand, workforce recommendations
      varied considerably across specialties. CONCLUSIONS: We know little about the
      distribution of the pediatric subspecialty workforce relative to the demand for
      their services. Given concerns about the adequacy of the pediatric subspecialty
      workforce, future research should assess the availability of these physicians
      relative to need for their services and account for nonclinical activities in
      workforce projections.

PMID- 15583102
TI  - Clinical features of patients with Kawasaki disease whose parents had the same
      disease.
AB  - OBJECTIVE: To observe the clinical characteristics of patients with Kawasaki
      disease whose parent also had the same disorder. DESIGN: Cross-sectional study
      using the data from nationwide surveys of Kawasaki disease in Japan. SETTING: All
      hospitals with a bed capacity of 100 or more and pediatric departments in Japan.
      PATIENTS: All patients described on the 16th and 17th surveys covering the 4-year
      period from January 1, 1999, through December 31, 2002. MAIN OUTCOME MEASURES: We
      compared clinical details, including sibling case, recurrence, diagnosis,
      administration of intravenous immunoglobulin, and coronary abnormalities, between
      patients whose parents had Kawasaki disease and patients with no parental history
      of Kawasaki disease. We also observed age at onset and sex of affected parent
      offspring pairs with Kawasaki disease confirmed by using the data of previous
      nationwide surveys. RESULTS: The odds for having sibling cases were significantly
      increased among patients whose parents also had Kawasaki disease (odds ratio,
      6.94; 95% confidence interval, 2.77-17.38). Patients with parental Kawasaki
      disease were more likely to experience recurrent Kawasaki disease, receive
      additional administration of intravenous immunoglobulin, and experience coronary
      abnormalities at 1 month after onset. Among confirmed parent-offspring pairs with
      Kawasaki disease, the mean age at onset of offspring was younger than that of
      their parents (25.6 vs 41.8 months), despite the lack of statistical
      significance. CONCLUSIONS: Some cases of Kawasaki disease show familial
      susceptibility to the disorder. Family history, especially parental history of
      Kawasaki disease, may be an indicator of disease severity.

PMID- 15583103
TI  - High-altitude pulmonary edema in children with underlying cardiopulmonary
      disorders and pulmonary hypertension living at altitude.
AB  - BACKGROUND: Pulmonary hypertension has not been described as a predisposing risk
      factor for high-altitude pulmonary edema (HAPE) in children. Previous studies
      have shown an association of HAPE with abnormally increased pulmonary
      vasoreactivity to hypoxia but generally normal pulmonary artery pressure (PAP)
      after recovery. OBJECTIVE: To describe HAPE of relatively rapid onset and its
      management in a series of children residing at moderate to high altitudes, all of
      whom had underlying pulmonary hypertension. METHODS AND RESULTS: From 1997 to
      2003, 30 children came to our center with high-altitude illness. Of these, 10
      children (aged 4-18 years; male-female ratio, 8:2) living at moderate to high
      altitudes (1610-3050 m) underwent cardiac catheterization after recovery from
      HAPE, and all were found to have chronic pulmonary hypertension (mean PAP, 38 +/-
      9 mm Hg; pulmonary vascular resistance, 8.6 +/- 2.8 U x m2). Increases in PAP and
      pulmonary vascular resistance to hypoxia (16% oxygen) suggest that these children
      have a reactive pulmonary pressor response and hence are susceptible to HAPE. Six
      of the 10 patients had predisposing cardiopulmonary abnormalities, and 5 of these
      6 patients did not receive a diagnosis prior to the onset of HAPE. Long-term
      treatment with calcium channel blockers, bosentan, sildenafil citrate, and/or
      oxygen lowered PAP, improved symptoms, and prevented the recurrence of HAPE.
      CONCLUSION: Children living at altitude who develop HAPE should undergo screening
      for diagnosis of underlying cardiopulmonary abnormalities including pulmonary
      hypertension.

PMID- 15583104
TI  - Long-term lower extremity prosthetic costs in children with traumatic lawnmower
      amputations.
AB  - OBJECTIVES: To evaluate prosthetic costs of pediatric lawnmower amputations; to
      see if reducing the incidence of pediatric lawnmower amputations could result in
      significant cost savings; and to consider if a cost analysis could be useful to
      implement more safety features (voluntarily or legislatively). DESIGN: Pediatric
      lawnmower amputees from 1980 to 2000 were reviewed to determine age at time of
      injury, level of amputation, number of prostheses, and lifetime per prosthesis. A
      standard prosthetic program beginning at amputation and ending at age 18 years
      was constructed. An aggregate cost was calculated according to the proportion of
      amputation levels. The cost burden for prosthetic care was estimated from the
      statistics of US pediatric lawnmower injuries. SETTING: Referral pediatric
      orthopedic center. PATIENTS: Fifty-three lower extremity amputees with 58 lower
      extremity amputations at a mean +/- SD age of 4.7 +/- 2.5 years were reviewed.
      RESULTS: The percentage of amputee children injured by riding lawnmowers was 80%;
      the percentage injured by riding lawnmowers engaged in reverse was 39%.
      Prosthetic costs from the time of injury to the age of 18 years range from 73,140
      dollars to 116,040 dollars per single lower extremity amputation. With 600 to 650
      new childhood amputations per year due to lawnmowers, the new annual burden for
      prosthetic costs thus ranges from 43.88 to 75.42 million dollars, or (600)(73,140
      dollars) to (650)(116,040 dollars). CONCLUSIONS: Further encouragement of
      lawnmower manufacturers to install improved safety devices (such as those to
      disengage power while in reverse mode of operation), new research on improved
      safety measures, and continued promotion of educational campaigns regarding the
      dangers of children being around and/or operating riding lawnmowers and garden
      tractors should be pursued. This will result in significant cost savings as well
      as incalculable health savings.

PMID- 15583105
TI  - Measuring public costs associated with loss of confidentiality for adolescents
      seeking confidential reproductive health care: How high the costs? How heavy the
      burden?

PMID- 15583106
TI  - Studies of the pediatric subspecialty workforce: overexposed and underexposed
      snapshots in time.

PMID- 15583107
TI  - Sex differences in morbidity and mortality among children with perinatally
      acquired human immunodeficiency virus infection in new york city.

PMID- 15583109
TI  - The cure of folly.

PMID- 15583110
TI  - Using survey results to improve the validity of the standard psychiatric
      nomenclature.
AB  - Measuring the validity of psychiatric diagnoses is still an unsolved problem.
      Yet, revisions of the Diagnostic and Statistical Manual of Mental Disorders and
      of chapter V of the International Classification of Diseases are now under way,
      with the hope of improving the validity of the current systems. This article
      suggests data that could be used to assist in this goal. This article has 3
      objectives. (1) To show that although the validity of the interview protocols
      used in collecting epidemiologic survey data has not itself been proven, the data
      banks they have collected are well suited to raising questions about the validity
      of the existing diagnostic nomenclature. This is the case because they faithfully
      operationalize the current nomenclature in large interview studies of diverse
      general populations. (2) To show the kinds of changes that appropriate analysis
      of these data may suggest as ways to improve the validity of the nomenclature.
      (3) To show how suggested changes that emerge from such analyses should be tested
      to learn whether they actually improve validity before they are implemented. The
      data sets from large epidemiologic studies have hardly been tapped for testing
      the validity of the current nomenclature. It is feasible to use them for this
      purpose because they are in the public domain and because they assess the
      presence or absence of each of the criteria in the manuals before applying the
      manuals' algorithms for combining them to make a diagnosis. Thus, these data
      banks allow exploration of the effects of combining and splitting diagnoses, of
      omitting criteria or reweighting them, and of choosing altered algorithms with
      respect to age at onset, number of symptoms, and duration of episodes. Assessing
      the consequences of these alterations can be tested by applying some of the
      criteria of Robins and Guze and Kendell.

PMID- 15583111
TI  - Challenges in operationalizing the DSM-IV clinical significance criterion.
AB  - BACKGROUND: An explicit clinical significance (CS) criterion was added to many
      DSM-IV diagnoses in an attempt to more closely approximate the clinical
      diagnostic process and reduce the proportion of false positives in
      epidemiological studies. The American Indian Service Utilization, Psychiatric
      Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP) offered a unique
      opportunity to examine the success of this effort. OBJECTIVE: To determine the
      impact of distress, impairment, and help-seeking reported in a lay structured
      interview on concordance with a clinical reappraisal. Further, to test the
      efficacy of 5 operationalizations of CS on the concordance and prevalence of DSM
      IV lifetime disorders. DESIGN: Completed between 1997 and 2000, a cross-sectional
      probability sample survey with clinical reappraisal of approximately 10% of
      participants. SETTING: General community. PARTICIPANTS: A population-based sample
      of 3084 members of 2 American Indian tribal groups, who were between the ages of
      15 and 54 years and resided on or near their home reservations, were randomly
      sampled from the tribal rolls and participated in structured psychiatric
      interviews. Clinical reappraisals were conducted with approximately 10% of the
      lay-interview participants. The response rate for the lay interview was 75%, and
      for the clinical reappraisal it was 72%. MAIN OUTCOMES MEASURES: The AI-SUPERPFP
      Composite International Diagnostic Interview (CIDI), a culturally adapted version
      of the CIDI, University of Michigan version. Adapted to assess DSM-IV diagnoses,
      questions assessing the CS criterion were inserted in all diagnostic modules. The
      Structured Clinical Interview for DSM-III-R (SCID) was used in the clinical
      reappraisal. RESULTS: Most participants who qualified as having AI-SUPERPFP CIDI
      lifetime disorders reported at least moderate levels of distress or impairment.
      Evidence of increased concordance between the CIDI and the SCID was lacking when
      more restrictive operationalizations of CS were used; indeed, the CIDI was very
      likely to underdiagnose disorders compared with the SCID (false negatives).
      Concomitantly, the CS operationalizations affected prevalence rates dramatically.
      CONCLUSION: The CS criterion, at least as operationalized to date, demonstrates
      little effectiveness in increasing the validity of diagnoses using lay
      administered structured interviews.

PMID- 15583112
TI  - The efficacy of short-term psychodynamic psychotherapy in specific psychiatric
      disorders: a meta-analysis.
AB  - BACKGROUND: The efficacy of psychodynamic therapy is controversial. Previous meta
      analyses have reported discrepant results. OBJECTIVE: To test the efficacy of
      short-term psychodynamic psychotherapy (STPP) in specific psychiatric disorders
      by performing a meta-analysis of more recent studies. We assessed outcomes in
      target problems, general psychiatric symptoms, and social functioning. DESIGN: We
      identified studies of STPP published between January 1, 1970, and September 30,
      2004, by means of a computerized search using MEDLINE, PsychINFO, and Current
      Contents. Rigorous inclusion criteria, included randomized controlled trials, use
      of treatment manuals and insurance of treatment integrity, therapists experienced
      or specifically trained in STPP, treatment of patients with specific psychiatric
      disorders, reliable and valid diagnostic measures, and data necessary to
      calculate effect sizes. Studies of interpersonal therapy were excluded. Seventeen
      studies fulfilled the inclusion criteria. The information was extracted by 3
      raters. Effect sizes were calculated for target problems, general psychiatric
      symptoms, and social functioning using the data published in the original
      studies. To examine the stability of outcome, we assessed effect sizes separately
      for end of therapy and follow-up assessment. The effect sizes of STPP were
      compared with those of waiting-list control patients, treatments as usual, and
      other forms of psychotherapy. RESULTS: Short-term psychodynamic psychotherapy
      yielded significant and large pretreatment-posttreatment effect sizes for target
      problems (1.39), general psychiatric symptoms (0.90), and social functioning
      (0.80). These effect sizes were stable and tended to increase at follow-up (1.57,
      0.95, and 1.19, respectively). The effect sizes of STPP significantly exceeded
      those of waiting-list controls and treatments as usual. No differences were found
      between STPP and other forms of psychotherapy. CONCLUSIONS: Short-term
      psychodynamic psychotherapy proved to be an effective treatment in psychiatric
      disorders. However, further research of STPP in specific psychiatric disorders is
      needed, including a study of the active ingredients of STPP. Effectiveness
      studies should be included.

PMID- 15583113
TI  - Contextual predictors of mental health service use among children open to child
      welfare.
AB  - BACKGROUND: Children involved with child welfare systems are at high risk for
      emotional and behavioral problems. Many children with identified mental health
      problems do not receive care, especially ethnic/minority children. OBJECTIVE: To
      examine how patterns of specialty mental health service use among children
      involved with child welfare vary as a function of the degree of coordination
      between local child welfare and mental health agencies. DESIGN: Specialty mental
      health service use for 1 year after contact with child welfare was examined in a
      nationally representative cohort of children aged 2 to 14 years. Predictors of
      service use were modeled at the child/family and agency/county levels. Child- and
      agency-level data were collected between October 15, 1999, and April 30, 2001.
      SETTING: Ninety-seven US counties. PARTICIPANTS: A total of 2823 child welfare
      cases (multiple informants) from the National Survey of Child and Adolescent Well
      being and agency-level key informants from the participating counties. MAIN
      OUTCOME MEASURES: Specialty mental health service use during the year after
      contact with the child welfare system. RESULTS: Only 28.3% of children received
      specialty mental health services during the year, although 42.4% had clinical
      level Child Behavior Checklist scores. Out-of-home placement, age, and
      race/ethnicity were strong predictors of service use rates, even after
      controlling for Child Behavior Checklist scores. Increased coordination between
      local child welfare and mental health agencies was associated with stronger
      relationships between Child Behavior Checklist scores and service use and
      decreased differences in rates of service use between white and African American
      children. CONCLUSIONS: Younger children and those remaining in their homes could
      benefit from increased specialty mental health services. They have
      disproportionately low rates of service use, despite high levels of need.
      Increases in interagency coordination may lead to more efficient allocation of
      service resources to children with the greatest need and to decreased
      racial/ethnic disparities.

PMID- 15583114
TI  - Immigration and lifetime prevalence of DSM-IV psychiatric disorders among Mexican
      Americans and non-Hispanic whites in the United States: results from the National
      Epidemiologic Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: There exist no national prevalence data on specific DSM-IV Axis I
      psychiatric disorders among foreign-born and US-born Mexican Americans and non
      Hispanic whites. OBJECTIVE: To present nationally representative data on the
      prevalence of DSM-IV lifetime psychiatric disorders among foreign-born and US
      born Mexican Americans and non-Hispanic whites. DESIGN: Face-to-face survey
      conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related
      Conditions. SETTING: The United States and District of Columbia, including Alaska
      and Hawaii. PARTICIPANTS: Household and group-quarters residents, aged 18 years
      and older (n = 43 093). MAIN OUTCOME MEASURES: Prevalence of DSM-IV substance use
      disorders and mood and anxiety disorders. RESULTS: With few exceptions, foreign
      born Mexican Americans and foreign-born non-Hispanic whites were at significantly
      lower risk (P<.05) of DSM-IV substance use and mood and anxiety disorders
      compared with their US-born counterparts. Although the risk of specific
      psychiatric disorders was similar between foreign-born Mexican Americans and
      foreign-born non-Hispanic whites, US-born Mexican Americans were at significantly
      lower risk (P<.05) of psychiatric morbidity than US-born non-Hispanic whites.
      CONCLUSIONS: Data favoring foreign-born Mexican Americans with respect to mental
      health may extend to foreign-born non-Hispanic whites. Future research among
      foreign-born and US-born Mexican Americans and the foreign-born and US-born of
      other origins and descents is needed to understand what appears to be the
      protective effects of culture and the deleterious effects of acculturation on
      psychiatric morbidity in the United States.

PMID- 15583115
TI  - Metyrapone as additive treatment in major depression: a double-blind and placebo
      controlled trial.
AB  - BACKGROUND: Inhibitors of steroid synthesis have been reported to exert
      antidepressive effects, according to preliminary findings. OBJECTIVE: To test
      whether the addition of metyrapone to standard antidepressants induces a more
      rapid, more efficacious, and sustained treatment response in patients with major
      depression. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING:
      Hospitalized care. PATIENTS: Sixty-three inpatients with a DSM-IV diagnosis of
      major depression and a baseline score 18 points or higher on the Hamilton Rating
      Scale for Depression. INTERVENTIONS: Random allocation to 2 treatment groups
      receiving either placebo or metyrapone (1 g/d) for the first 3 weeks during a 5
      week treatment with standard serotonergic antidepressants (nefazodone or
      fluvoxamine). MAIN OUTCOME MEASURES: Primary outcome criteria were the number of
      responders and the time to onset of action. Responder rates were considered twice
      after 3 and 5 weeks with a definition of treatment response as 30% and 50%
      reduction, respectively, of baseline Hamilton Rating Scale for Depression scores.
      Onset of action was defined as the time point at which at least a 20% reduction
      of baseline Hamilton Rating Scale for Depression scores occurred. RESULTS: Using
      intention-to-treat analysis, we found that a higher proportion of patients
      receiving metyrapone showed a positive treatment response at day 21 (23 of 33
      patients) and at day 35 (19 of 33 patients) compared with placebo patients (day
      21: 13 of 30 patients; Fisher exact P = .031; day 35: 10 of 30 patients; Fisher
      exact P = .047). The clinical course of patients treated with metyrapone showed
      an earlier onset of action (Kaplan-Meier analysis; log-rank test P<.006)
      beginning in the first week. The plasma concentrations of corticotropin and
      deoxycortisol were significantly higher during metyrapone treatment (multivariate
      analysis of covariance, P<.05), whereas cortisol remained largely unchanged.
      Metyrapone treatment was well tolerated without serious adverse effects.
      CONCLUSIONS: Metyrapone is an effective adjunct in the treatment of major
      depression, accelerating the onset of antidepressant action. A better treatment
      outcome compared with standard treatment and a sustained antidepressive effect
      were observed.

PMID- 15583116
TI  - A family study of alcohol dependence: coaggregation of multiple disorders in
      relatives of alcohol-dependent probands.
AB  - BACKGROUND: Alcohol dependence tends to aggregate within families. We analyzed
      data from the family collection of the Collaborative Study on the Genetics of
      Alcoholism to quantify familial aggregation using several different criterion
      sets. We also assessed the aggregation of other psychiatric disorders in the same
      sample to identify areas of possible shared genetic vulnerability. DESIGN: Age
      corrected lifetime morbid risk was estimated in adult first-degree relatives of
      affected probands and control subjects for selected disorders. Diagnostic data
      were gathered by semistructured interview (the Semi-Structured Assessment for the
      Genetics of Alcoholism), family history, and medical records. Rates of illness
      were corrected by validating interview and family history reports against senior
      clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity,
      cohort effects, and site of ascertainment were also taken into account. RESULTS:
      Including data from 8296 relatives of alcoholic probands and 1654 controls, we
      report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in
      relatives of probands and controls, respectively; respective rates were 37.0% and
      20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any
      DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and
      5.2% for antisocial personality disorder. Rates of specific substance dependence
      were markedly increased in relatives of alcohol-dependent probands for cocaine,
      marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen
      for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder,
      and major depression. CONCLUSIONS: The risk of alcohol dependence in relatives of
      probands compared with controls is increased about 2-fold. The aggregation of
      antisocial personality disorder, drug dependence, anxiety disorders, and mood
      disorders suggests common mechanisms for these disorders and alcohol dependence
      within some families. These data suggest new phenotypes for molecular genetic
      studies and alternative strategies for studying the heterogeneity of alcohol
      dependence.

PMID- 15583117
TI  - Habit learning in Tourette syndrome: a translational neuroscience approach to a
      developmental psychopathology.
AB  - BACKGROUND: The etiology of Tourette syndrome (TS) involves disturbances in the
      structure and function of the basal ganglia. The basal ganglia mediate habit
      learning. OBJECTIVE: To study habit learning in persons with TS. DESIGN: Patients
      with TS were compared with normal controls in performance on a probabilistic
      classification, or habit-learning task (weather prediction). SETTING: University
      research institute. PARTICIPANTS: One hundred twenty-three children and adults,
      56 with a diagnosis of TS and 67 healthy control subjects. MAIN OUTCOME MEASURES:
      Habit learning was assessed by the extent of improvement in accuracy of
      predictions and reaction times over trial blocks during performance of the
      weather prediction task. Declarative learning was assessed by performance on 3
      tasks that required intact declarative memory functioning. RESULTS: Children with
      TS were impaired at habit learning relative to normal controls (P = .01). This
      finding was replicated in the independent sample of adults with TS (P = .01). The
      rate of learning correlated inversely with the severity of tic symptoms across
      both samples (r = -0.34; P = .01). Thus, impaired learning accompanied more
      severe symptoms. Measures of declarative memory functioning, in contrast, were
      normal in the TS groups. CONCLUSIONS: Striatal learning systems are uniquely
      dysfunctional in both children and adults with TS. The correlation of habit
      learning with symptom severity suggests that the number and severity of tics are
      a function of the degree to which the system for habit learning is dysfunctional.
      Thus, both the deficits in habit learning and the tic symptoms of TS are likely
      to be consequences of the previously reported anatomical and functional
      disturbances of the striatum in children and adults who have TS. The existence of
      a well-developed animal model for this learning system, which permits study of
      the neural and molecular bases of habit learning, has important implications for
      the neurobiological study of TS and for the development of new or improved
      therapeutics for this condition.

PMID- 15583118
TI  - Brain serotonin transporter binding potential measured with carbon 11-labeled
      DASB positron emission tomography: effects of major depressive episodes and
      severity of dysfunctional attitudes.
AB  - BACKGROUND: Although brain serotonin transporter (5-HTT) density has been
      investigated in subjects with a history of major depressive episodes (MDE), there
      has never been an investigation of brain 5-HTT during a current MDE. Brain 5-HTT
      binding potential (BP) may have an important role during MDE due to major
      depressive disorder, because the 5-HTT regulates extracellular 5-HT. The BP is an
      index of receptor density. Carbon 11-labeled 3-amino-4-(2-dimethylaminomethyl
      phenylsulfanyl)-benzonitrile (DASB) positron emission tomography (PET) is the
      first brain imaging technique that can measure the 5-HTT BP in cortical and
      subcortical brain regions in vivo. The purposes of this study were to investigate
      5-HTT BP during MDE and to determine the relationship between 5-HTT BP and
      negativistic dysfunctional attitudes during MDE. Dysfunctional attitudes are
      negatively biased assumptions and beliefs regarding oneself, the world, and the
      future. Our recent publication of increased serotonin2 BP in MDE with severely
      negativistic dysfunctional attitudes suggests that this subgroup of MDE subjects
      has very low levels of extracellular serotonin. METHODS: Regional 5-HTT BP was
      measured in 20 nonsmoking medication-free (> or =3 months) depressed subjects and
      20 age-matched nonsmoking, medication-free, healthy subjects using [11C]DASB PET.
      Dysfunctional attitudes were measured using the Dysfunctional Attitudes Scale.
      RESULTS: No difference in regional 5-HTT BP was found between MDE and healthy
      subjects; however, the subgroup of MDE subjects with highly negativistic
      dysfunctional attitudes had significantly higher 5-HTT BP compared with healthy
      subjects in brain regions mainly sampling serotonergic nerve terminals
      (prefrontal cortex, anterior cingulate, thalamus, bilateral caudate, and
      bilateral putamen; average, 21% greater; F(1,26), 5.6-12.2 [P values, .03-.002]).
      In the MDE subjects, increased 5-HTT BP was strongly associated with more
      negativistic dysfunctional attitudes in brain regions primarily sampling
      serotonergic nerve terminals (prefrontal cortex, anterior cingulate, thalamus,
      caudate, and putamen; r = 0.64-0.74 [P values, .003 to <.001]). CONCLUSIONS:
      Serotonin transporters play an important role during depression. The magnitude of
      regional 5-HTT BP can provide a vulnerability to low levels of extracellular
      serotonin and symptoms of extremely negativistic dysfunctional attitudes.

PMID- 15583120
TI  - Biography of J. Clark Lagarias.

PMID- 15583121
TI  - Inhaling to mitigate exhaled bioaerosols.
AB  - Humans commonly exhale aerosols comprised of small droplets of airway-lining
      fluid during normal breathing. These "exhaled bioaerosols" may carry airborne
      pathogens and thereby magnify the spread of certain infectious diseases, such as
      influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize
      that, by altering lung airway surface properties through an inhaled nontoxic
      aerosol, we might substantially diminish the number of exhaled bioaerosol
      droplets and thereby provide a simple means to potentially mitigate the spread of
      airborne infectious disease independently of the identity of the airborne
      pathogen or the nature of any specific therapy. We find that some normal human
      subjects expire many more bioaerosol particles than other individuals during
      quiet breathing and therefore bear the burden of production of exhaled
      bioaerosols. Administering nebulized isotonic saline to these "high-producer"
      individuals diminishes the number of exhaled bioaerosol particles expired by
      72.10 +/- 8.19% for up to 6 h. In vitro and in vivo experiments with saline and
      surfactants suggest that the mechanism of action of the nebulized saline relates
      to modification of the physical properties of the airway-lining fluid, notably
      surface tension.

PMID- 15583122
TI  - Fragile X syndrome: (What's) lost in translation?

PMID- 15583123
TI  - A multiple-levels-of-analysis approach to the study of developmental processes in
      maltreated children.

PMID- 15583124
TI  - Heterogeneous evolutionary processes affect R gene diversity in natural
      populations of Solanum pimpinellifolium.
AB  - Resistance (R) genes of plants are responsible for pathogen recognition and
      encode proteins that trigger a cascade of responses when a pathogen invades a
      plant. R genes are assumed to be under strong selection, but there is limited
      knowledge of the processes affecting R gene diversity in the wild. In this study,
      DNA sequence variation of Cf-2 homologs was surveyed in populations of Solanum
      pimpinellifolium, a wild relative of the cultivated tomato. The Cf-2 locus is
      involved in resistance to strains of the fungus Cladosporium fulvum. At least 26
      different Cf-2 homologs were detected in natural populations of S.
      pimpinellifolium. These homologs differ by single base pair substitutions as well
      as indels in regions coding for leucine-rich repeats. Molecular population
      genetic analyses suggest that natural selection has acted heterogeneously on Cf-2
      homologs, with selection against amino acid substitutions occurring in the 5'
      portion of the genes, and possible restricted positive selection in the 3' end.
      Balancing selection may have maintained haplotypes at the 5' end of the genes.
      Limited sequence exchange between genes has also contributed to sequence
      variation. S. pimpinellifolium individuals differ in the number of Cf-2 homologs
      they contain, obscuring the relationships of orthology and paralogy. This survey
      of Cf-2 variation in S. pimpinellifolium illustrates the wealth of R gene
      diversity that exists in wild plant populations, as well as the complexity of
      interacting genetic and evolutionary processes that generate such diversity.

PMID- 15583125
TI  - Phi value versus psi analysis.

PMID- 15583126
TI  - Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal
      diabetes plus neurological features.
AB  - Inwardly rectifying potassium channels (Kir channels) control cell membrane K(+)
      fluxes and electrical signaling in diverse cell types. Heterozygous mutations in
      the human Kir6.2 gene (KCNJ11), the pore-forming subunit of the ATP-sensitive
      (K(ATP)) channel, cause permanent neonatal diabetes mellitus (PNDM). For some
      mutations, PNDM is accompanied by marked developmental delay, muscle weakness,
      and epilepsy (severe disease). To determine the molecular basis of these
      different phenotypes, we expressed wild-type or mutant (R201C, Q52R, or V59G)
      Kir6.2/sulfonylurea receptor 1 channels in Xenopus oocytes. All mutations
      increased resting whole-cell K(ATP) currents by reducing channel inhibition by
      ATP, but, in the simulated heterozygous state, mutations causing PNDM alone
      (R201C) produced smaller K(ATP) currents and less change in ATP sensitivity than
      mutations associated with severe disease (Q52R and V59G). This finding suggests
      that increased K(ATP) currents hyperpolarize pancreatic beta cells and impair
      insulin secretion, whereas larger K(ATP) currents are required to influence
      extrapancreatic cell function. We found that mutations causing PNDM alone impair
      ATP sensitivity directly (at the binding site), whereas those associated with
      severe disease act indirectly by biasing the channel conformation toward the open
      state. The effect of the mutation on ATP sensitivity in the heterozygous state
      reflects the different contributions of a single subunit in the Kir6.2 tetramer
      to ATP inhibition and to the energy of the open state. Our results also show that
      mutations in the slide helix of Kir6.2 (V59G) influence the channel kinetics,
      providing evidence that this domain is involved in Kir channel gating, and
      suggest that the efficacy of sulfonylurea therapy in PNDM may vary with genotype.

PMID- 15583127
TI  - Common scale-invariant patterns of sleep-wake transitions across mammalian
      species.
AB  - Although mammals of different species have different sleep patterns, brief sleep
      wake transitions commonly are observed across species and appear to occur
      randomly throughout the sleeping period. The dynamical patterns and functions of
      these brief awakenings from sleep are not well understood, and they often are
      viewed as disruptions (random or pathologic) of the sleep process. In this
      article, we hypothesize that brief awakenings from sleep may reflect aspects of
      the endogenous sleep control mechanism and thus may exhibit certain robust
      dynamical patterns across species. We analyze sleep recordings from mice, rats,
      cats, and humans, and we compare the distributions of sleep and wake episode
      durations. For all four species, we find that durations of brief wake episodes
      during the sleep period exhibit a scale-free power-law behavior with an exponent
      alpha that remains the same for all species (alpha approximately equal to 2.2).
      In contrast, sleep episode durations for all four species follow exponential
      distributions with characteristic time scales, which change across species in
      relation to body mass and metabolic rate. Our findings suggest common dynamical
      features of brief awakenings and sleep durations across species and may provide
      insights into the dynamics of the neural circuits controlling sleep.

PMID- 15583128
TI  - In silico study of amyloid beta-protein folding and oligomerization.
AB  - Experimental findings suggest that oligomeric forms of the amyloid beta protein
      (Abeta) play a critical role in Alzheimer's disease. Thus, elucidating their
      structure and the mechanisms of their formation is critical for developing
      therapeutic agents. We use discrete molecular dynamics simulations and a four
      bead protein model to study oligomerization of two predominant alloforms, Abeta40
      and Abeta42, at the atomic level. The four-bead model incorporates backbone
      hydrogen-bond interactions and amino acid-specific interactions mediated through
      hydrophobic and hydrophilic elements of the side chains. During the simulations
      we observe monomer folding and aggregation of monomers into oligomers of variable
      sizes. Abeta40 forms significantly more dimers than Abeta42, whereas pentamers
      are significantly more abundant in Abeta42 relative to Abeta40. Structure
      analysis reveals a turn centered at Gly-37-Gly-38 that is present in a folded
      Abeta42 monomer but not in a folded Abeta40 monomer and is associated with the
      first contacts that form during monomer folding. Our results suggest that this
      turn plays an important role in Abeta42 pentamer formation. Abeta pentamers have
      a globular structure comprising hydrophobic residues within the pentamer's core
      and hydrophilic N-terminal residues at the surface of the pentamer. The N termini
      of Abeta40 pentamers are more spatially restricted than Abeta42 pentamers.
      Abeta40 pentamers form a beta-strand structure involving Ala-2-Phe-4, which is
      absent in Abeta42 pentamers. These structural differences imply a different
      degree of hydrophobic core exposure between pentamers of the two alloforms, with
      the hydrophobic core of the Abeta42 pentamer being more exposed and thus more
      prone to form larger oligomers.

PMID- 15583129
TI  - Catalysis of protein folding by chaperones in pathogenic bacteria.
AB  - Molecular chaperones are thought to inhibit off-pathway interactions such as
      aggregation from occurring without influencing the on-pathway formation of native
      structure. Here, we present a mechanism whereby the family of PapD-like
      chaperones, which are involved in the formation of adhesive pili in pathogenic
      bacteria, function by suppressing aggregation while simultaneously catalyzing the
      folding of subunits that make up the pilus. We also show that the Arg-8 residue,
      invariant in the cleft of all known PapD-like chaperones, makes up part of the
      active site of the chaperone. The data argue for a temporal mechanism of
      catalyzed folding. The terminal carboxylate group of a pilus subunit anchors to
      the active site of the chaperone by hydrogen bonding. This bonding spatially
      fixes the COOH terminus of the subunit in the correct context for beta-sheet
      formation, using the edge of the NH(2)-terminal domain of the chaperone as a
      nucleation site.

PMID- 15583130
TI  - Reversed voltage-dependent gating of a bacterial sodium channel with proline
      substitutions in the S6 transmembrane segment.
AB  - Members of the voltage-gated-like ion channel superfamily have a conserved pore
      structure. Transmembrane helices that line the pore (M2 or S6) are thought to
      gate it at the cytoplasmic end by bending at a hinge glycine residue. Proline
      residues favor bending of alpha-helices, and substitution of proline for this
      glycine (G219) dramatically stabilizes the open state of a bacterial Na(+)
      channel NaChBac. Here we have probed S6 pore-lining residues of NaChBac by
      proline mutagenesis. Five of 15 proline-substitution mutants yielded
      depolarization-activated Na(+) channels, but only G219P channels have strongly
      negatively shifted voltage dependence of activation, demonstrating specificity
      for bending at G219 for depolarization-activated gating. Remarkably, three
      proline-substitution mutations on the same face of S6 as G219 yielded channels
      that activated upon hyperpolarization and inactivated very slowly. Studies of
      L226P showed that hyperpolarization to -147 mV gives half-maximal activation, 123
      mV more negative than WT. Analysis of combination mutations and studies of block
      by the local anesthetic etidocaine favored the conclusion that hyperpolarization
      activated gating results from opening of the cytoplasmic gate formed by S6
      helices. Substitution of multiple amino acids for L226 indicated that
      hyperpolarization-activated gating was correlated with a high propensity for
      bending, whereas depolarization-activated gating was favored by a low propensity
      for bending. Our results further define the dominant role of bending of S6 in
      determining not only the voltage dependence but also the polarity of voltage
      dependent gating. Native hyperpolarization-activated gating of hyperpolarization-
      and cyclic nucleotide-gated (HCN) channels in animals and KAT channels in plants
      may involve bending at analogous S6 amino acid residues.

PMID- 15583131
TI  - The kidney-specific WNK1 isoform is induced by aldosterone and stimulates
      epithelial sodium channel-mediated Na+ transport.
AB  - WNK1 belongs to a unique family of Ser/Thr kinases that have been implicated in
      the control of blood pressure. Intronic deletions in the WNK1 gene result in its
      overexpression and lead to pseudohypoaldosteronism type II, a disease with salt
      sensitive hypertension and hyperkalemia. How overexpression of WNK1 leads to
      Na(+) retention and hypertension is not entirely clear. Similarly, there is no
      information on the hormonal regulation of expression of WNK kinases. There are
      two main WNK1 transcripts expressed in the kidney: the originally described
      "long" WNK1 and a shorter transcript that is specifically expressed in the kidney
      (KS-WNK1). The goal of this study was to determine the effect of aldosterone, the
      main hormonal regulator of Na(+) homeostasis, on the transcription of WNK1
      isoforms in renal target cells, by using an unique mouse cortical collecting duct
      cell line that stably expresses functional mineralocorticoid receptors. Our
      results demonstrate that aldosterone, at physiological concentrations, rapidly
      induces the expression of the KS-WNK1 but not that of the long-WNK1 in these
      cells. Importantly, stable overexpression of KS-WNK1 significantly increases
      transepithelial Na(+) transport in cortical collecting duct cells. Similarly,
      coexpression of KS-WNK1 and the epithelial Na(+) channel in Fischer rat thyroid
      epithelial cells also stimulates Na(+) current, suggesting that KS-WNK1 affects
      the subcellular location or activity but not the expression of epithelial Na(+)
      channel. These observations suggest that stimulation of KS-WNK1 expression might
      be an important element of aldosterone-induced Na(+) retention and hypertension.

PMID- 15583132
TI  - Toward an evolutionary perspective on conceptual representation: species-specific
      calls activate visual and affective processing systems in the macaque.
AB  - Non-human primates produce a diverse repertoire of species-specific calls and
      have rich conceptual systems. Some of their calls are designed to convey
      information about concepts such as predators, food, and social relationships, as
      well as the affective state of the caller. Little is known about the neural
      architecture of these calls, and much of what we do know is based on single-cell
      physiology from anesthetized subjects. By using positron emission tomography in
      awake rhesus macaques, we found that conspecific vocalizations elicited activity
      in higher-order visual areas, including regions in the temporal lobe associated
      with the visual perception of object form (TE/TEO) and motion (superior temporal
      sulcus) and storing visual object information into long-term memory (TE), as well
      as in limbic (the amygdala and hippocampus) and paralimbic regions (ventromedial
      prefrontal cortex) associated with the interpretation and memory-encoding of
      highly salient and affective material. This neural circuitry strongly corresponds
      to the network shown to support representation of conspecifics and affective
      information in humans. These findings shed light on the evolutionary precursors
      of conceptual representation in humans, suggesting that monkeys and humans have a
      common neural substrate for representing object concepts.

PMID- 15583133
TI  - Cell-surface expression of a mutated Epstein-Barr virus glycoprotein B allows
      fusion independent of other viral proteins.
AB  - Epstein-Barr virus (EBV) infects human B lymphocytes and epithelial cells. We
      have compared the requirements for EBV glycoprotein-induced cell fusion between
      Chinese hamster ovary effecter cells and human B lymphoblasts or epithelial cells
      by using a virus-free cell fusion assay. EBV-encoded gB, gH, gL, and gp42
      glycoproteins were required for efficient B cell fusion, whereas EBV gB, gH, and
      gL glycoproteins were required for Chinese hamster ovary effecter cell fusion
      with epithelial cell lines (AGS and SCC68) or the human embryonic kidney cell
      line 293-P. Fusion with human embryonic kidney 293-P cells was greater than
      fusion observed with B cells, indicative of an important role for cell contact.
      An antibody directed against the gH and gL complex inhibited epithelial cell
      fusion. Increased surface expression of gB alone as a result of truncations or
      point mutants in the carboxyl-terminal tail allowed gB-mediated fusion with
      epithelial cells, albeit at a lower level than with coexpression of gB, gH, and
      gL. Overall, gB appears to be the critical component for EBV glycoprotein
      mediated cell fusion.

PMID- 15583134
TI  - The Saccharomyces cerevisiae aquaporin Aqy1 is involved in sporulation.
AB  - Aquaporins mediate rapid selective water transport across biological membranes.
      Elucidation of their precise physiological roles promises important insight into
      cellular and organismal osmoregulation. The genome of the yeast Saccharomyces
      cerevisiae encodes two similar but differentially regulated aquaporins. Here, we
      show that expression of AQY1 is stimulated during sporulation and that the Aqy1
      protein is detectable exclusively in spore membranes. When spores are rapidly
      frozen, those that lack Aqy1 survive better, providing for a functional test of
      active spore water channels. Under ambient conditions, lack of Aqy1 reduces spore
      fitness. Because this reduction is independent from germination conditions, Aqy1
      may be important during spore formation rather than subsequent maintenance or
      germination. Indeed, it seems that Aqy1 is degraded after spores have been formed
      and during germination. Taken together, Aqy1 is developmentally controlled and
      may play a role in spore maturation, probably by allowing water outflow. Taken
      together, we demonstrate a functional role of an aquaporin in gametogenesis, as
      well as in the formation of durable structures such as spores, a role that may
      have wider biological and medical implications.

PMID- 15583135
TI  - Use of herpes simplex virus and pseudorabies virus chimeric glycoprotein D
      molecules to identify regions critical for membrane fusion.
AB  - Membrane fusion induced by herpes simplex virus (HSV) requires the action of four
      viral membrane glycoproteins (gB, gD, gH, and gL) and the binding of gD to one of
      its receptors, such as the herpesvirus entry mediator or nectin-1. The related
      animal herpesvirus, pseudorabies virus (PRV), encodes a homologous set of
      glycoproteins and its gD can also use nectin-1 as an entry receptor. We show here
      that PRV gD, when coexpressed with HSV gB, gH, and gL, cannot substitute for HSV
      gD in inducing fusion with target cells expressing nectin-1. Chimeric gD
      molecules composed of HSV and PRV sequences can substitute, provided the first
      285 aa are from HSV gD. Because the first 261 aa were sufficient for receptor
      binding, this suggested that amino acids 262-285 contain a region required for
      cell fusion but not for receptor binding. Deletions from amino acids 250-299
      failed to identify a specific subregion critical for cell fusion, except possibly
      for amino acids 250-255, which also influenced receptor binding. Instead,
      presence of a flexible stalk between the membrane and receptor-binding domain
      appears to be required, perhaps to enable conformational changes in gD on
      receptor binding and subsequent interactions of undefined regions of gD with the
      other glycoproteins required for membrane fusion.

PMID- 15583136
TI  - Evidence that injury-induced changes in hippocampal neuronal calcium dynamics
      during epileptogenesis cause acquired epilepsy.
AB  - Alterations in hippocampal neuronal Ca(2+) and Ca(2+)-dependent systems have been
      implicated in mediating some of the long-term neuroplasticity changes associated
      with acquired epilepsy (AE). However, there are no studies in an animal model of
      AE that directly evaluate alterations in intracellular calcium concentration
      ([Ca(2+)](i)) and Ca(2+) homeostatic mechanisms (Ca(2+) dynamics) during the
      development of AE. In this study, Ca(2+) dynamics were evaluated in acutely
      isolated rat CA1 hippocampal, frontal, and occipital neurons in the pilocarpine
      model by using [Ca(2+)](i) imaging fluorescence microscopy during the injury
      (acute), epileptogenesis (latency), and chronic-epilepsy phases of the
      development of AE. Immediately after status epilepticus (SE), hippocampal
      neurons, but not frontal and occipital neurons, had significantly elevated
      [Ca(2+)](i) compared with saline-injected control animals. Hippocampal neuronal
      [Ca(2+)](i) remained markedly elevated during epileptogenesis and was still
      elevated indefinitely in the chronic-epilepsy phase but was not elevated in SE
      animals that did not develop AE. Inhibiting the increase in [Ca(2+)](i) during SE
      with the NMDA channel inhibitor MK801 was associated in all three phases of AE
      with inhibition of the changes in Ca(2+) dynamics and the development of AE.
      Ca(2+) homeostatic mechanisms in hippocampal neurons also were altered in the
      brain-injury, epileptogenesis, and chronic-epilepsy phases of AE. These results
      provide evidence that [Ca(2+)](i) and Ca(2+)-homeostatic mechanisms are
      significantly altered during the development of AE and suggest that altered
      Ca(2+) dynamics may play a role in the induction and maintenance of AE and
      underlie some of the neuroplasticity changes associated with the epileptic
      phenotype.

PMID- 15583137
TI  - Transport of Drosophila fragile X mental retardation protein-containing
      ribonucleoprotein granules by kinesin-1 and cytoplasmic dynein.
AB  - Transport and translation of mRNA are tightly coupled to ensure strict temporal
      and spatial expression of nascent proteins. Fragile X mental retardation protein
      (FMRP) has been shown to be involved in translational regulation and is found in
      ribonucleoprotein (RNP) granules that travel along dendrites of neurons. In this
      study, GFP-tagged Drosophila homologue of FMRP (dFMR) was used to visualize RNP
      granule movement in Drosophila S2 cells. GFP-dFMR form granules that contain both
      endogenous dFMR and mRNA. Live fluorescence microscopy revealed that dFMR
      containing RNP granules move bidirectionally in thin processes formed by S2 cells
      in the presence of cytochalasin D. Knocking down the heavy chains of either
      kinesin-1 (kinesin heavy chain) or cytoplasmic dynein (dynein heavy chain) by RNA
      interference blocks the movement of the dFMR granules. In contrast, knockdown of
      kinesin light chain (KLC), which is typically necessary for movement of membrane
      organelles by kinesin-1, had no effect on the dFMR granule translocation. In
      immunoprecipitation assays, dFMR associates with both kinesin heavy chain and
      dynein heavy chain, but not KLC. Based on these findings, we conclude that dFMR
      containing RNP granules are moved by both kinesin-1 and cytoplasmic dynein and
      that KLC is not essential and is likely missing from RNP-transporting kinesin-1.

PMID- 15583138
TI  - Molecular and genetic analysis of disseminated neoplastic cells in
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a multisystem disorder of women, characterized
      by cystic degeneration of the lungs, renal angiomyolipomas (AML), and lymphatic
      abnormalities. LAM lesions result from the proliferation of benign-appearing,
      smooth muscle-like LAM cells, which are characterized by loss of heterozygosity
      (LOH) of one of the tuberous sclerosis complex (TSC) genes. LAM cells are
      believed to migrate among the involved organs. Because of the apparently
      metastatic behavior of LAM, we tried to isolate LAM cells from body fluids. A
      cell fraction separated by density gradient centrifugation from blood had TSC2
      LOH in 33 of 60 (55%) LAM patients. Cells with TSC2 LOH were also found in urine
      from 11 of 14 (79%) patients with AML and in chylous fluid from 1 of 3 (33%)
      patients. Identification of LAM cells with TSC2 LOH in body fluids was not
      correlated with severity of lung disease or extrapulmonary involvement and was
      found in one patient after double lung transplantation. These studies are
      compatible with a multisite origin for LAM cells. They establish the existence of
      disseminated, potentially metastatic LAM cells through a relatively simple,
      noninvasive procedure that should be valuable for molecular and genetic studies
      of somatic mutations in LAM and perhaps other metastatic diseases.

PMID- 15583139
TI  - Structure of the complex between the cytosolic chaperonin CCT and phosducin-like
      protein.
AB  - The three-dimensional structure of the complex formed between the cytosolic
      chaperonin CCT (chaperonin containing TCP-1) and phosducin (Pdc)-like protein
      (PhLP), a regulator of CCT activity, has been solved by cryoelectron microscopy.
      Binding of PhLP to CCT occurs through only one of the chaperonin rings, and the
      protein does not occupy the central folding cavity but rather sits above it
      through interactions with two regions on opposite sides of the ring. This causes
      the apical domains of the CCT subunits to close in, thus excluding access to the
      folding cavity. The atomic model of PhLP generated from several atomic structures
      of the homologous Pdc fits very well with the mass of the complex attributable to
      PhLP and predicts the involvement of several sequences of PhLP in CCT binding.
      Binding experiments performed with PhLP/Pdc chimeric proteins, taking advantage
      of the fact that Pdc does not interact with CCT, confirm that both the N- and C
      terminal domains of PhLP are involved in CCT binding and that several regions
      suggested by the docking experiment are indeed critical in the interaction with
      the cytosolic chaperonin.

PMID- 15583141
TI  - Genome update: correlation of bacterial genomic properties.

PMID- 15583140
TI  - RNA interference acts as a natural antiviral response to O'nyong-nyong virus
      (Alphavirus; Togaviridae) infection of Anopheles gambiae.
AB  - RNA interference (RNAi) is triggered in eukaryotic organisms by double-stranded
      RNA (dsRNA), and it destroys any mRNA that has sequence identity with the dsRNA
      trigger. The RNAi pathway in Anopheles gambiae can be silenced by transfecting
      cells with dsRNA derived from exon sequence of the A. gambiae Argonaute2 (AgAgo2)
      gene. We hypothesized that RNAi may also act as an antagonist to alphavirus
      replication in A. gambiae because RNA viruses form dsRNA during replication.
      Silencing AgAgo2 expression would make A. gambiae mosquitoes more permissive to
      virus infection. To determine whether RNAi conditions the vector competence of A.
      gambiae for O'nyong-nyong virus (ONNV), we engineered a genetically modified ONNV
      that expresses enhanced GFP (eGFP) as a marker. After intrathoracic injection,
      ONNV-eGFP slowly spread to other A. gambiae tissues over a 9-day incubation
      period. Mosquitoes were then coinjected with virus and either control beta
      galactosidase dsRNA (dsbetagal; note that "ds" is used as a prefix to indicate
      the dsRNA derived from a given gene throughout) or ONNV dsnsP3. Treatment with
      dsnsP3 inhibited virus spread significantly, as determined by eGFP expression
      patterns. ONNV-eGFP titers from mosquitoes coinjected with dsnsP3 were
      significantly lower at 3 and 6 days after injection than in mosquitoes coinjected
      with dsbetagal. Mosquitoes were then coinjected with ONNV-eGFP and dsAgAgo2.
      Mosquitoes coinjected with virus and AgAgo2 dsRNA displayed widespread eGFP
      expression and virus titers 16-fold higher than dsbetagal controls after 3 or 6
      days after injection. These observations provide direct evidence that RNAi is an
      antagonist of ONNV replication in A. gambiae, and they suggest that the innate
      immune response conditions vector competence.

PMID- 15583142
TI  - Polymerization of C-terminally truncated Mycobacterium tuberculosis FtsZ is
      unlikely to be physiologically relevant.

PMID- 15583143
TI  - The C-terminally truncated MtFtsZ-DeltaC169 mutant of Mycobacterium tuberculosis
      FtsZ shows GTPase and GTP-induced, GTP-specific polymerization activities in
      vitro.

PMID- 15583144
TI  - The difficulty of annotating genes: the case of putrescine carbamoyltransferase.

PMID- 15583145
TI  - Helicobacter pylori heat-shock protein 60 induces inflammatory responses through
      the Toll-like receptor-triggered pathway in cultured human gastric epithelial
      cells.
AB  - Contact between Helicobacter pylori and gastric epithelial cells results in
      activation of NF-kappaB followed by secretion of interleukin (IL)-8. However,
      host-cell receptor(s) and their ligands involved in H. pylori-related IL-8
      production have yet to be fully defined. In this study, the interaction between
      Toll-like receptors (TLRs), which are host receptors for pathogens involved in
      the innate immune response, and heat-shock protein (HSP) 60, an immune-potent
      antigen of H. pylori, was examined during H. pylori-induced IL-8 secretion in
      vitro. Recombinant H. pylori HSP60 (rHpHSP60) was prepared and added to cultured
      KATO III human gastric epithelial cells with or without pre-incubation with mouse
      monoclonal anti-TLR2 or anti-TLR4 antibodies. IL-8 mRNA expression and IL-8
      protein release were analysed by Northern blotting and immunoassay. Involvement
      of NF-kappaB activation was analysed immunocytochemically by anti-NF-kappaB p65
      antibody and ammonium pyrrolidinedithiocarbamate (PDTC), an inhibitor of NF
      kappaB-mediated transcriptional activation. rHpHSP60 induced IL-8 mRNA expression
      and IL-8 secretion in a dose-dependent manner in KATO III cells. Anti-TLR2
      antibody inhibited rHpHSP60-induced IL-8 secretion by 75 %, and anti-TLR4
      antibody inhibited it by 30 %. rHpHSP60 induced nuclear translocation of NF
      kappaB p65, which was inhibited by pretreatment with anti-TLR2 antibody.
      Treatment with PDTC significantly decreased the secretion of IL-8 induced by
      rHpHSP60. These findings suggest that H. pylori HSP60 activates NF-kappaB and
      induces IL-8 production through TLR-triggered pathways in gastric epithelial
      cells. Thus, it is possible that H. pylori HSP60 and TLR interaction in host
      cells contributes to the development of gastric inflammation caused by H. pylori
      infection.

PMID- 15583146
TI  - Identification of a haem-utilization protein (Hup) in Haemophilus influenzae.
AB  - Haemophilus influenzae has an absolute growth requirement for a porphyrin source.
      This growth requirement can be satisfied in vitro by haem, haemoglobin or the
      haemoglobin-haptoglobin, haem-haemopexin and haem-albumin complexes. A family of
      proteins, termed the Hgp proteins, which are essential for utilization of the
      haemoglobin-haptoglobin complex, has previously been identified. A strain lacking
      the Hgp proteins also has a residual ability to utilize haemoglobin, indicating
      that additional moieties contribute to haemoglobin utilization. Using a
      haemoglobin affinity method an approximately 105 kDa protein was isolated.
      Mutation of the identified gene in an Hgp null background reduced the ability of
      the mutant strain to utilize haemoglobin in vitro. The mutation also resulted in
      a reduced ability to utilize haem, haem-haemopexin, haem-albumin and haemoglobin
      haptoglobin, thus identifying a general haem-utilization protein (Hup) in
      Haemophilus influenzae.

PMID- 15583147
TI  - Production and characterization of murine monoclonal antibodies against
      Haemophilus parasuis and study of their protective role in mice.
AB  - Monoclonal antibodies (MAbs) against Haemophilus parasuis were obtained by the
      fusion of SP2/0-Ag14 murine myeloma cells and spleen cells from BALB/c mice
      immunized with a whole-bacterial-cell suspension (WC) of H. parasuis strain SW124
      (serotype 4). Two MAbs showing strong reactivity in ELISA were further
      characterized using SDS-PAGE and Western-blot assays. Different treatments of the
      WC indicated that MAbs 4D5 and 4G9 identified epitopes of proteinic and
      polysaccharidic nature, respectively. Electron microscopic examination revealed
      that, unlike the proteinic epitopes, the lipopolysaccharidic epitopes were
      exposed on the surface of the cell. Using coagglutination, Western-blot and dot
      blot assays it was found that both MAbs recognized common epitopes of all the
      reference strains and field isolates of H. parasuis. None of the other bacteria
      tested reacted with the MAbs. These results indicated that both the proteinic and
      polysaccharidic antigens carried species-specific epitopes. It is suggested that
      these MAbs may potentially be useful for identification of H. parasuis isolates
      as well as for developing serological diagnostic tools. MAbs 4D5 and 4G9 were
      unable to kill H. parasuis in vitro in the presence of complement. However, an
      enhanced bacterial clearance from blood was observed in mice inoculated with
      either of the MAbs. Highly significant protection was observed in mice using MAb
      4G9. This is believed to be the first report of MAbs capable of identifying
      common species-specific antigens of H. parasuis and of their implication in
      protection against challenge infection in mice.

PMID- 15583148
TI  - The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is
      upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is
      not required for virulence.
AB  - The Yersinia pseudotuberculosis chromosome contains a seven-gene polycistronic
      unit (the pmrF operon) whose products share extensive homologies with their pmrF
      counterparts in Salmonella enterica serovar Typhimurium (S. typhimurium), another
      Gram-negative bacterial enteropathogen. This gene cluster is essential for
      addition of 4-aminoarabinose to the lipid moiety of LPS, as demonstrated by MALDI
      TOF mass spectrometry of lipid A from both wild-type and pmrF-mutated strains. As
      in S. typhimurium, 4-aminoarabinose substitution of lipid A contributes to in
      vitro resistance of Y. pseudotuberculosis to the antimicrobial peptide polymyxin
      B. Whereas pmrF expression in S. typhimurium is mediated by both the PhoP-PhoQ
      and PmrA-PmrB two-component regulatory systems, it appears to be PmrA-PmrB
      independent in Y. pseudotuberculosis, with the response regulator PhoP
      interacting directly with the pmrF operon promoter region. This result reveals
      that the ubiquitous PmrA-PmrB regulatory system controls different regulons in
      distinct bacterial species. In addition, pmrF inactivation in Y.
      pseudotuberculosis has no effect on bacterial virulence in the mouse, again in
      contrast to the situation in S. typhimurium. The marked differences in pmrF
      operon regulation in these two phylogenetically close bacterial species may be
      related to their dissimilar lifestyles.

PMID- 15583149
TI  - Characterization of the Bacillus cereus Nhe enterotoxin.
AB  - The non-haemolytic enterotoxin (Nhe) is one of two three-component enterotoxins
      responsible for the diarrhoeal food-poisoning syndrome caused by Bacillus cereus.
      Nhe is composed of NheA, NheB and NheC. The three genes encoding the Nhe
      components constitute an operon, and the transcriptional start site is located 61
      bp upstream of the nheA translational start site. The nhe genes were cloned
      separately, and expressed in either Bacillus subtilis or Escherichia coli.
      Separate expression showed that all three components were required for biological
      activity. In addition, NheA and NheB were purified from B. cereus culture
      supernatants. As NheC seems to be expressed in only small amounts by B. cereus,
      NheC was expressed and purified as a histidine-tagged fusion protein. The maximum
      cytotoxic activity was obtained when the molar ratio between NheA : NheB : His6
      NheC was 10 : 10 : 1, and it was shown that NheB was the binding component of the
      enterotoxin complex.

PMID- 15583150
TI  - Identification of residues in the Pseudomonas aeruginosa elastase propeptide
      required for chaperone and secretion activities.
AB  - An important virulence factor of the opportunistic human pathogen Pseudomonas
      aeruginosa is elastase, a secreted thermolysin-like neutral zinc-metalloprotease
      (TNP). Elastase is synthesized as a larger precursor with an amino-terminal 18
      kDa propeptide, and was the first TNP shown to require its propeptide as an
      intramolecular chaperone (IMC) for activity and secretion. This paper reports the
      analysis of the elastase propeptide to identify residues conserved among other
      TNP precursors that may be critical for its IMC function. The prosequences of TNP
      precursors from both Gram-negative (Vibrio species and Legionella species) and
      Gram-positive (Bacillus species) bacteria were found to show homology to the
      elastase propeptide. Two regions of conserved residues were observed: a
      hydrophilic region (ProM) found in the middle of the elastase propeptide and a
      more hydrophobic region (ProC) located proximal to the propeptide-processing
      site. To test whether such conserved motifs were important to function, single
      residue substitutions at eight conserved amino acids were introduced within the
      full-length pre-proelastase precursor by site-specific mutagenesis of lasB, the
      gene encoding elastase. Mutant lasB alleles were expressed from plasmids within a
      lasB-deleted P. aeruginosa strain, FRD740, and the effects of these propeptide
      alterations on elastase enzyme activity, processing, stability and accumulation
      inside and outside of the cell were examined. Within the ProM region,
      substitution at Arg74 resulted in a dramatic accumulation of proelastase in the
      cell, suggesting a secretion defect, and a dramatic reduction in supernatant
      elastolytic activity. Substitution at Asn68 adversely affected the amount of
      elastase in the culture supernatant, apparently as a result of the reduced
      stability of the mutated proelastase in the cell. Within the ProC region,
      mutations at Ile181 and Ala183 abolished the accumulation of a stable elastase
      molecule in the supernatant. Most mutations produced a phenotype consistent with
      a defect in protein folding and stability. Overall, the data from this
      preliminary study show that conserved residues within the elastase propeptide are
      essential for its function and begin to define the mechanisms of action of IMCs
      in the TNP family.

PMID- 15583151
TI  - Siderophore and haem iron use by Tritrichomonas foetus.
AB  - The ability of the parasitic flagellate Tritrichomonas foetus to use various iron
      sources for its physiological requirements was studied. The siderophores
      ferrioxamine B, ferrichrome, triacetylfusarinine, coprogen, enterobactin and
      pyoverdine sustained growth of the cells under iron-limited conditions, and
      siderophore iron was incorporated into the major iron protein of T. foetus,
      ferredoxin. The kinetics of siderophore uptake by the cells indicated that a non
      saturable transport is involved, unlike the uptake of a ferrous salt. Siderophore
      uptake by the cells did not involve extracellular reductive dissociation of the
      ferric chelates, although T. foetus cells had some ferrireductase activity on
      ferric citrate. Fluorescent analogues of siderophores were used to show that the
      siderophores taken up by the cells were in small intracellular vesicles. The
      fluorescence emission maximum of pyoverdine in these intracellular vesicles
      shifted from 460 nm to 530 nm, indicating a very acidic environment. The results
      suggest that a wide range of chemically unrelated siderophores can be taken up
      non-specifically and efficiently used by T. foetus; the mechanism involved may be
      pinocytosis and removal of the iron from the siderophores in acidic intracellular
      vesicles. Haemin also sustained the growth of T. foetus cells under iron-limited
      conditions. The use of haemin iron by the cells probably involves haem oxygenase,
      since traces of biliverdin were found in the medium when haemin was the iron
      source. The iron uptake and ferrireductase activities of the cells do not seem to
      be regulated by the amounts of iron and copper in the growth medium.

PMID- 15583152
TI  - Cross-complementation between the products of the genes P1 and ORF6 of Mycoplasma
      pneumoniae subtypes 1 and 2.
AB  - The genes P1 (MPN141) and ORF6 (MPN142) are essential for the successful
      colonization of the human respiratory tract by Mycoplasma pneumoniae. Both genes
      are located in the P1 operon, which consists of three genes. The P1 gene is the
      second gene in the operon, followed by the ORF6 gene. The P1 gene contains two
      (RepMP2/3, RepMP4) and the ORF6 gene one (RepMP5) specific repetitive DNA
      sequence, of which seven to nine similar but not identical copies are dispersed
      on the genome. Despite this large potential pool for genetic variation, M.
      pneumoniae isolates from patients contain only one of two distinct combinations
      of the genes P1 and ORF6. To analyse the functions of the repetitive DNA
      sequences, two 'new' combinations of the genes P1 and ORF6 were constructed,
      keeping the P1 gene constant but exchanging RepMP5 copies of the ORF6 gene. M.
      pneumoniae was transformed with these constructs and the transformants were
      tested for their ability to grow and survive under in vitro conditions and in
      guinea pigs. The two transformants colonized the respiratory tract of guinea pigs
      and showed no obvious differences in their growth behaviour compared to M.
      pneumoniae isolates from patients. The results indicate that the subtype-specific
      combinations of the repetitive elements in the P1 and ORF6 genes are not
      essential for the successful adherence of M. pneumoniae to host cells and the
      colonization of the respiratory tract of guinea pigs.

PMID- 15583153
TI  - Cell surface differentiation of Mycoplasma mobile visualized by surface protein
      localization.
AB  - Mycoplasma mobile has a flask-shaped cell morphology and glides toward its
      tapered end at a rate of 3-7 cell lengths per s (2.0-4.5 microm s(-1)) by an
      unknown mechanism. Gliding requires that the surface of the cell is in contact
      with a solid substrate, such as glass or plastic. In order to characterize the
      nature of the outer surface of M. mobile, monoclonal antibodies were raised
      against intact cells and screened for their ability to recognize surface
      proteins. Four antibodies were identified and their protein targets were
      determined. One antibody recognized the Gli349 protein, which is known to be
      involved in glass binding and gliding. This antibody was also able to displace
      attached M. mobile cells from glass, suggesting that Gli349 is the major adhesion
      protein in M. mobile. The other three antibodies recognized members of the Mvsp
      family of proteins, which are presumably the major surface antigens of M. mobile.
      Immunofluorescence studies were performed to localize these proteins on the
      surface of M. mobile cells. Gli349 localized to the proximal region of the
      tapered part of the cell (the 'neck'), while the various Mvsp family members
      showed several distinct patterns of subcellular localization. MvspN and MvspO
      localized to the distal end of the tapered part of the cell (the 'head'), MvspK
      localized to the main part of the cell (the 'body'), and MvspI localized to both
      the head and body but not the neck. This analysis shows that M. mobile
      surprisingly expresses multiple versions of its major surface antigen at once but
      differentiates its surface by differential localization of the various
      paralogues.

PMID- 15583154
TI  - Variability of a glucose phosphotransferase system permease in Mycoplasma
      mycoides subsp. mycoides Small Colony.
AB  - Intraclonal antigenic variation in pathogenic mycoplasma species is considered an
      important feature of host-pathogen interaction. Such intraclonal protein
      variation was observed for the interaction of Mycoplasma mycoides subsp. mycoides
      Small Colony, the agent of contagious bovine pleuropneumonia, with mAb 3F3.
      Colony immunostaining allows the definition of 3F3 ON- and 3F3 OFF-type variants,
      which revert at low frequency. Targets of mAb 3F3 were shown to be surface
      located, and resided on multiple polypeptides in the 58-68 kDa size range. Phage
      display and a genomic database were combined to determine the gene encoding the
      proteins recognized by mAb 3F3. A gene encoding the putative permease of the
      glucose phosphotransferase system was identified. Genome sequence analysis of
      strain PG1 revealed two highly similar copies of this gene, resulting from
      duplication of the chromosomal region carrying the gene. Southern blot analysis
      demonstrated the presence of this duplication in almost every African strain
      tested, but not in European strains. DNA analysis revealed that ON/OFF switching
      is governed by a base substitution occurring upstream of the coding region for
      the 3F3 epitope. This event generates a stop codon that results in the premature
      termination of the PtsG protein.

PMID- 15583155
TI  - New endophytic isolates of Muscodor albus, a volatile-antibiotic-producing
      fungus.
AB  - Muscodor albus, an endophytic fungus originally isolated from Cinnamomum
      zeylanicum, produces a mixture of volatile organic compounds (VOCs) in culture
      and its spectrum of antimicrobial activity is broad. Using the original isolate
      of M. albus as a selection tool, it has been possible to find other culturally
      and biochemically unique wild-type isolates of this organism existing as
      endophytes in a variety of other plant species, including Grevillea pterifolia
      (fern-leafed grevillea), Kennedia nigriscans (snake vine) and Terminalia
      prostrata (nanka bakarra) growing in the northern reaches of the Northern
      Territory of Australia. Interestingly, none of the new isolates had a culture
      morphology that was identical to the original isolate, nevertheless each
      possessed hyphal characteristics that resembled that isolate. Furthermore, their
      ITS-5.8S rDNA sequences were 96-99 % identical to that of M. albus and the
      isolates were considered M. albus on the basis of the DNA sequence data. However,
      the VOCs produced by these new isolates greatly differed in quality from the
      original strain by virtue of the production of naphthalene, naphthalene, 1,1'
      oxybis-, and one or more other compounds. In bioassays with a range of test micro
      organisms, including fungi and bacteria, each isolate possessed biological
      activity but the range of activity was great. Artificial mixtures of some of the
      VOCs mimicked the effects of the VOCs of the fungus. The value of these
      observations to the biology and practical uses of M. albus in agriculture and
      other applications is discussed.

PMID- 15583156
TI  - Microarray analysis of Cryphonectria parasitica Galpha- and Gbetagamma-signalling
      pathways reveals extensive modulation by hypovirus infection.
AB  - Using an established spotted cDNA microarray platform, the nature of changes in
      the transcriptional profiles of 2200 unique genes from the chestnut blight fungus
      Cryphonectria parasitica in response to the absence of either the Galpha subunit
      CPG-1 or the Gbeta subunit CPGB-1 has been explored. It is reported that 216
      transcripts were altered in accumulation in the Deltacpg-1 strain and 163 in the
      Deltacpgb-1 strain, with a considerable overlap (100 genes) that were changed in
      both cases. Of note, these commonly altered transcripts were changed in the same
      direction in every instance, thus suggesting a considerable redundancy in pathway
      control or extensive crosstalk. To further knowledge of the potential impact on G
      protein-signalling of infection by hypovirus CHV1-EP713, the accumulation of CPG
      1 and CPGB-1 was also investigated by Western analysis. It was demonstrated that
      both signalling components were reduced in abundance to approximately 25 % of
      wild-type levels, while their transcripts were slightly elevated. Comparison of a
      list of genes with altered expression in the presence of CHV1-EP713 to the data
      obtained in the absence of either G-protein subunit showed that more than one
      half of all the transcripts changed by hypovirus infection were also changed in
      at least one G-protein mutant strain, with one-third being changed in both.
      Significantly, 95 % of the co-changed genes were altered in the same direction.
      These data provide the first evidence for modulation of Gbeta protein levels as
      well as the Gbetagamma-signalling pathways by hypovirus infection, and support
      the hypothesis that modification of G-protein-signalling via both Galpha and
      Gbetagamma provides for a significant contribution to hypovirus-mediated
      phenotype.

PMID- 15583157
TI  - Distribution and characterization of staphylococcal interspersed repeat units
      (SIRUs) and potential use for strain differentiation.
AB  - Variable-number tandem repeats (VNTRs) have been shown to be a powerful tool in
      the determination of evolutionary relationships and population genetics of
      bacteria. The sequencing of a number of Staphylococcus aureus genomes has allowed
      the identification of novel VNTR sequences in S. aureus, which are similar to
      those used in the study of the evolution of Mycobacterium tuberculosis clades.
      Seven VNTRs, termed staphylococcal interspersed repeat units (SIRUs), distributed
      around the genome are described, occurring in both unique and multiple sites, and
      varying in length from 48 to 159 bp. Variations in copy numbers were observed in
      all loci, within both the sequenced genomes and the UK epidemic methicillin
      resistant S. aureus (EMRSA) isolates. Clonally related UK EMRSA isolates were
      clustered using SIRUs, which provided a greater degree of discrimination than
      multi-locus sequence typing, indicating that VNTRs may be a more appropriate
      evolutionary marker for studying transmission events and the geographical spread
      of S. aureus clades.

PMID- 15583158
TI  - The Vibrio seventh pandemic island-II is a 26.9 kb genomic island present in
      Vibrio cholerae El Tor and O139 serogroup isolates that shows homology to a 43.4
      kb genomic island in V. vulnificus.
AB  - Vibrio cholerae is the aetiological agent of the deadly diarrhoeal disease
      cholera. In this study the 7.5 kb Vibrio seventh pandemic island-II (VSP-II) that
      is unique to V. cholerae El Tor and O139 serogroups was analysed and it was found
      to be part of a novel 26.9 kb genomic island (GEI) encompassing VC0490-VC0516.
      The low-GC-content VSP-II encompassed 24 predicted ORFs, including DNA repair and
      methyl-accepting chemotaxis proteins, a group of hypothetical proteins and a
      bacteriophage-like integrase adjacent to a tRNA gene. Interestingly, V. cholerae
      ORFs VC0493-VC0498, VC0504-VC0510 and VC0516, which encodes an integrase, were
      homologous to Vibrio vulnificus strain YJ016 ORFs VV0510-VV0516, VV0518-VV0525
      and VV0560, which also encodes an integrase, respectively. Some ORFs showed amino
      acid identities greater than 90 % between the two species in these regions. In V.
      vulnificus strain YJ016, a 43.4 kb low-GC-content (43 %) GEI encompassing ORFs
      VV0509-VV0560 was identified and named V. vulnificus island-I (VVI-I). The 52
      ORFs of VVI-I included a phosphotransferase system gene cluster, genes required
      for sugar metabolism and transposase genes. There was synteny and homology
      between the 5' region of V. cholerae VSP-II and the 5' region of V. vulnificus
      VVI-I; however, VVI-I contained an additional 31.5 kb of DNA between VV0526 and
      VV0560 in strain YJ016. A second V. vulnificus strain, CMCP6, did not contain the
      43.4 kb VVI-I; in this strain two ORFs were found between the 5' and 3' flanking
      genes VV10636 and VV10632, showing 100 % identity to VV0508 and VV0561,
      respectively, which flank VVI-I.

PMID- 15583159
TI  - Evidence that the Rhizobium regulatory protein RirA binds to cis-acting iron
      responsive operators (IROs) at promoters of some Fe-regulated genes.
AB  - Mutations in rirA of Rhizobium have been shown to deregulate expression of
      several genes that are normally repressed by iron. A conserved sequence, the iron
      responsive operator (IRO), was identified near promoters of vbsC (involved in the
      synthesis of the siderophore vicibactin), rpoI (specifies an ECF sigma factor
      needed for vicibactin synthesis) and the two fhuA genes (encoding vicibactin
      receptor). Removal of these IRO sequences abolished Fe-responsive repression.
      Most of these genes were constitutively expressed in the heterologous host,
      Paracoccus denitrificans, but introduction of the cloned rirA gene repressed
      expression of these Rhizobium genes in this heterologous host if the
      corresponding IRO sequences were also intact. These observations are the first to
      examine the mechanisms of RirA, which has no sequence similarity to well-known
      iron-responsive regulators such as Fur or DtxR. They provide strong
      circumstantial evidence that RirA is a transcriptional regulator that binds to
      cis-acting regulatory sequences near the promoters of at least some of the genes
      whose expression it controls in response to Fe availability.

PMID- 15583160
TI  - Physical and genetic map of the Weissella paramesenteroides DSMZ 20288T
      chromosome and characterization of different rrn operons by ITS analysis.
AB  - The Weissella paramesenteroides DSMZ 20288T chromosome was analysed by pulsed
      field gel electrophoresis, enabling the construction of a physical and genetic
      map. A total of 21 recognition sites of the restriction enzymes AscI, I-CeuI,
      NotI and SfiI were mapped on the chromosome, which was found to be circular with
      an estimated size of 2026 kb. This is believed to constitute the first study into
      the genomic organization of a strain of this genus, addressing the localization
      of important chromosomal regions such as oriC and terC. A total of 23 genetic
      markers were mapped, including eight rrn operons that were precisely assigned in
      37 % of the W. paramesenteroides chromosome. The transcription direction of rrn
      loci was determined and three different rrn clusters were recognized regarding
      the presence/absence of tRNA genes in ITS regions.

PMID- 15583161
TI  - Characterization of a Myxococcus xanthus mutant that is defective for adventurous
      motility and social motility.
AB  - Myxococcus xanthus is a gliding bacterium that possesses two motility systems,
      the adventurous (A-motility) and social (S-motility) systems. A-motility is used
      for individual cell gliding, while S-motility is used for gliding in
      multicellular groups. Video microscopy studies showed that nla24 cells are non
      motile on agar surfaces, suggesting that the nla24 gene product is absolutely
      required for both A-motility and S-motility under these assay conditions. S
      motility requires functional type IV pili, wild-type LPS O-antigen, and an
      extracellular matrix of exopolysaccharide (EPS) and protein called fibrils. The
      results of expression studies and tethering assays indicate that the nla24 mutant
      has functional type IV pili. The nla24 mutant also produces wild-type LPS.
      However, several lines of evidence suggest that the nla24 mutant is defective for
      production of the EPS portion of the fibril matrix. The nla24 mutant is also
      defective for transcription of two genes (aglU and cglB) known to be required for
      A-motility, which is consistent with the idea that nla24 cells are defective for
      A-motility. Based on these findings, it is proposed that the putative
      transcriptional activator Nla24 regulates a subset of genes that are important
      for A-motility and S-motility in M. xanthus.

PMID- 15583162
TI  - Wzx proteins involved in biosynthesis of O antigen function in association with
      the first sugar of the O-specific lipopolysaccharide subunit.
AB  - One of the most common pathways for the export of O-specific lipopolysaccharide
      (LPS) across the plasma membrane requires the participation of the Wzx protein.
      Wzx belongs to a family of integral membrane proteins that share little
      conservation in their primary amino acid sequence, making it difficult to
      delineate functional domains. This paper reports the cloning and expression in
      Escherichia coli K-12 of various Wzx homologues from different bacteria as FLAG
      epitope-tagged protein fusions. A reconstitution system for O16 LPS synthesis was
      used to assess the ability of each Wzx protein to complement an E. coli K-12
      Deltawzx mutant. The results demonstrate that Wzx proteins from O-antigen systems
      that use N-acetylglucosamine or N-acetylgalactosamine for the initiation of the
      biosynthesis of the O repeat can fully complement the formation of O16 LPS.
      Partial complementation was seen with Wzx from Pseudomonas aeruginosa, a system
      that uses N-acetylfucosamine in the initiation reaction. In contrast, there was
      negligible complementation with the Wzx protein from Salmonella enterica, a
      system in which galactose is the initiating sugar. These results support a model
      whereby the first sugar of the O repeat can be recognized by the O-antigen
      translocation machinery.

PMID- 15583163
TI  - Denitrification and ammonia oxidation by Nitrosomonas europaea wild-type, and
      NirK- and NorB-deficient mutants.
AB  - The phenotypes of three different Nitrosomonas europaea strains--wild-type,
      nitrite reductase (NirK)-deficient and nitric oxide reductase (NorB)-deficient
      strains--were characterized in chemostat cell cultures, and the effect of nitric
      oxide (NO) on metabolic activities was evaluated. All strains revealed similar
      aerobic ammonia oxidation activities, but the growth rates and yields of the
      knock-out mutants were significantly reduced. Dinitrogen (N2) was the main
      gaseous product of the wild-type, produced via its denitrification activity. The
      mutants were unable to reduce nitrite to N2, but excreted more hydroxylamine
      leading to the formation of almost equal amounts of NO, nitrous oxide (N2O) and
      N2 by chemical auto-oxidation and chemodenitrification of hydroxylamine. Under
      anoxic conditions Nsm. europaea wild-type gains energy for growth via nitrogen
      dioxide (NO2)-dependent ammonia oxidation or hydrogen-dependent denitrification
      using nitrite as electron acceptor. The mutant strains were restricted to NO
      and/or N2O as electron acceptor and consequently their growth rates and yields
      were much lower compared with the wild-type. When cells were transferred from
      anoxic (denitrification) to oxic conditions, the wild-type strain endogenously
      produced NO and recovered ammonia oxidation within 8 h. In contrast, the mutant
      strains remained inactive. For recovery of ammonia oxidation activity the NO
      concentration had to be adjusted to about 10 p.p.m. in the aeration gas.

PMID- 15583164
TI  - Characterization of Bacillus subtilis gamma-glutamyltransferase and its
      involvement in the degradation of capsule poly-gamma-glutamate.
AB  - During early stationary phase, Bacillus subtilis NAFM5 produces capsular
      poly(gamma-glutamic acid) (gammaPGA, 2x10(6) Da), which contains D- and L
      glutamate, and then degrades it during late stationary phase. The gamma
      glutamyltransferase (EC 2.3.2.2; GGT) of this strain successively hydrolysed
      gammaPGA from the amino-terminal end, to yield both D- and L-glutamate. This
      enzyme was specifically synthesized during the stationary phase through
      transcriptional activation of the corresponding ggt gene by the ComQXPA quorum
      sensing system. A ggt knockout mutant degraded gammaPGA into 1x10(5) Da
      fragments, but not any further, indicating that the capsule gammaPGA is first
      internally degraded by an endo-type of gammaPGA hydrolase into 1x10(5) Da
      intermediates, then externally into glutamates via GGT. Due to its inability to
      generate the glutamates from the capsule, the ggt mutant sporulated more
      frequently than the wild-type strain. The results show that B. subtilis GGT has a
      powerful exo-gamma-glutamyl hydrolase activity that participates in capsule
      gammaPGA degradation to supply stationary-phase cells with constituent
      glutamates.

PMID- 15583165
TI  - Associations between Bacillus subtilis sigmaB regulators in cell extracts.
AB  - The general stress regulon of Bacillus subtilis is induced by the activation of
      the sigma(B) transcription factor. Activation of sigma(B) occurs as a consequence
      of the dephosphorylation of its positive regulator RsbV by one of two
      phosphatases that respond to either physical or nutritional stress. The physical
      stress phosphatase (RsbU) requires a second protein (RsbT) for activity. Stress
      is thought to initiate a process that triggers the release of RsbT from a large
      inhibitory complex composed of multiple copies of two protein species, RsbR
      (and/or its paralogues) and RsbS. The stress-derived signal driving RsbT release
      is unknown, but it fails to develop in B. subtilis lacking either ribosome
      protein L11 or the ribosome-associated protein Obg. RsbR, RsbS, RsbT, Obg and
      ribosomes elute in common high-molecular-mass fractions during gel-filtration
      chromatography of crude B. subtilis extracts. This paper reports the
      investigation of the basis of this coelution by the examining of associations
      between these proteins in extracts prepared from wild-type and mutant B.
      subtilis, and Escherichia coli engineered to express RsbR, RsbS and RsbT. Large
      RsbR/RsbS complexes, distinct from ribosomes, were detected in extracts of both
      B. subtilis and E. coli. In E. coli, high-molecular-mass forms of RsbS were less
      abundant when RsbR was absent, but in B. subtilis, only when both RsbR and its
      principal paralogues were missing from the extract was this form less abundant.
      This finding is consistent with the notion that the RsbR paralogues, present in
      B. subtilis but not E. coli, can substitute for RsbR in such complexes. RsbT was
      not bound to RsbR/RsbS in any extract that was examined, including one prepared
      from a B. subtilis strain with an RsbS variant (RsbS59SA) that is believed to
      continuously associate with RsbT. The high-molecular-mass forms of RsbT were
      found to be Triton-sensitive and independent of any other B. subtilis protein for
      their formation. These probably represent RsbT aggregates. The data suggest that
      the contribution of ribosomes/Obg to sigma(B) activation does not involve
      formation of a stable association between these proteins and the Rsb complex. In
      addition, the binding of RsbT to RsbS/RsbR appears to be more labile than the
      binding between the previously analysed Rsb proteins which form inhibitory
      complexes. This, and the apparent proclivity of RsbT to aggregate, suggests an
      inherent instability in RsbT which may play a role in its regulation.

PMID- 15583166
TI  - Transcriptional and translational analysis of the ccaR gene from Streptomyces
      clavuligerus.
AB  - CcaR is a positive-acting transcriptional regulator involved in cephamycin C and
      clavulanic acid biosynthesis in Streptomyces clavuligerus. Previous sequence
      analyses of the ccaR gene revealed two possible start codons, an ATG, and a GTG
      located in-frame 18 bp downstream of the ATG. To determine the true start codon,
      ccaR was expressed, either from the GTG or ATG codon, in Escherichia coli. A
      protein product was only obtained from the ATG construct. Similarly, ccaR
      constructs originating from ATG or GTG and designed for expression from a
      glycerol-regulated promoter in Streptomyces species were prepared and used to
      complement a S. clavuligerus ccaR mutant. Bioassays showed that only the ATG
      construct could complement the ccaR mutant to restore cephamycin C production,
      and Western analysis confirmed the presence of CcaR in the mutant complemented
      with the ATG construct only. To ensure that expression of ccaR from its native
      promoter also initiated at the ATG rather than GTG, a conservative point mutation
      was introduced into ccaR, converting the GTG to GTC. The GTC construct still
      fully complemented a ccaR mutant, confirming that ATG is the true start codon.
      Inspection of the region upstream of ccaR by S1 nuclease protection and primer
      extension analyses indicated the presence of two transcript start points that
      mapped to residues located 74 and 173 bp upstream of the ATG codon.

PMID- 15583167
TI  - Phycobilisome rod mutants in Synechocystis sp. strain PCC6803.
AB  - The phycobilisome is a large pigment-protein assembly that harvests light energy
      for photosynthesis. This supramolecular complex is composed of two main
      structures: a core substructure and peripheral rods. Linker polypeptides assemble
      phycobiliproteins within these structures and optimize light absorption and
      energy transfer. Mutations have been constructed in three rod-linker-coding genes
      located in the cpc operon of Synechocystis sp. strain PCC6803. The cpcC1 gene
      encoding the 33 kDa linker is found to be epistatic to cpcC2 encoding the 30 kDa
      linker, indicating a specific role for each of these two linkers in rod growth.
      This corroborates studies on the sequential degradation of phycobilisomes upon
      nitrogen starvation. Three allelic mutants affecting cpcC2 revealed a polar
      effect of commonly used cassettes (aphI, aadA) on the operon steady-state
      transcripts and an effect of rod linker availability on the amount of phycocyanin
      incorporated in the phycobilisome. This led to the proposal that regulation of
      rod length could occur through processing of transcripts upstream of the cpcC2
      gene.

PMID- 15583168
TI  - PST1 and ECM33 encode two yeast cell surface GPI proteins important for cell wall
      integrity.
AB  - Pst1p was previously identified as a protein secreted by yeast regenerating
      protoplasts, which suggests a role in cell wall construction. ECM33 encodes a
      protein homologous to Pst1p, and both of them display typical features of GPI
      anchored proteins and a characteristic receptor L-domain. Pst1p and Ecm33p are
      both localized to the cell surface, Pst1p being at the cell membrane and possibly
      also in the periplasmic space. Here, the characterization of pst1Delta,
      ecm33Delta and pst1Delta ecm33Delta mutants is described. Deletion of ECM33 leads
      to a weakened cell wall, and this defect is further aggravated by simultaneous
      deletion of PST1. As a result, the ecm33Delta mutant displays increased levels of
      activated Slt2p, the MAP kinase of the cell integrity pathway, and relies on a
      functional Slt2-mediated cell integrity pathway to ensure viability. Analyses of
      model glycosylated proteins show glycosylation defects in the ecm33Delta mutant.
      Ecm33p is also important for proper cell wall ultrastructure organization and,
      furthermore, for the correct assembly of the mannoprotein outer layer of the cell
      wall. Pst1p seems to act in the compensatory mechanism activated upon cell wall
      damage and, in these conditions, may partially substitute for Ecm33p.

PMID- 15583169
TI  - Characterization of a temperature-sensitive DNA ligase from Escherichia coli.
AB  - DNA ligases are essential enzymes in cells due to their ability to join DNA
      strand breaks formed during DNA replication. Several temperature-sensitive mutant
      strains of Escherichia coli, including strain GR501, have been described which
      can be complemented by functional DNA ligases. Here, it is shown that the ligA251
      mutation in E. coli GR501 strain is a cytosine to thymine transition at base 43,
      which results in a substitution of leucine by phenylalanine at residue 15. The
      protein product of this gene (LigA251) is accumulated to a similar level at
      permissive and non-permissive temperatures. Compared to wild-type LigA, at 20
      degrees C purified LigA251 has 20-fold lower ligation activity in vitro, and its
      activity is reduced further at 42 degrees C, resulting in 60-fold lower ligation
      activity than wild-type LigA. It is proposed that the mutation in LigA251 affects
      the structure of the N-terminal region of LigA. The resulting decrease in DNA
      ligase activity at the non-permissive temperature is likely to occur as the
      result of a conformational change that reduces the rate of adenylation of the
      ligase.

PMID- 15583170
TI  - Difference in kinetic behaviour of catechol 2,3-dioxygenase variants from a
      polluted environment.
AB  - In a previous environmental survey of a polluted area, the authors identified two
      catechol 2,3-dioxygenase (C23O) sequences predominant in environmental bacterial
      isolates mineralizing benzene and/or toluene and also in soil DNA extracts. In
      the present study, using information of stable operon arrangement and conserved
      gene sequences, the complete C23O ORFs of these two variants were cloned,
      sequenced and overexpressed. The variants differ in six nucleotide positions, and
      the putative protein sequences differ only by a single amino acid, Tyr or His, at
      position 218. Even though the three-dimensional model does not suggest a
      significant influence of such an amino acid substitution on enzyme function, the
      Tyr218 variant differed significantly from the His218 variant in lower turnover
      number and in lower apparent K(m) for catecholic substrates. These results are
      evidence of the importance for enzyme function of amino acids not directly
      influencing active site structure and prove the utility of recovering
      polymorphisms evolved and selected for special functions in natural ecosystems.

PMID- 15583171
TI  - Evolution of the PPM-family protein phosphatases in Streptomyces: duplication of
      catalytic domain and lateral recruitment of additional sensory domains.
AB  - Originally identified from eukaryotes, the Mg2+- or Mn2+-dependent protein
      phosphatases (PPMs) are a diverse group of enzymes whose members include
      eukaryotic PP2C and some prokaryotic serine/threonine phosphatases. In a previous
      study, unexpectedly large numbers of PPMs were identified in two Streptomyces
      genomes. In this work, a phylogenetic analysis was performed with all the PPMs
      available from a wide variety of microbial sources to determine the evolutionary
      origin of the Streptomyces PPM proteins. Consistent with earlier hypotheses, the
      results suggested that the microbial PPMs were relatively recent additions from
      eukaryotic sources. Results also indicated that the Streptomyces PPMs were
      divided into two major subfamilies at an early stage of their emergence in
      Streptomyces genomes. The first subfamily, which contains only six Streptomyces
      PPMs, possesses a catalytic domain whose sequence and architecture are similar to
      that of eukaryotic PPMs; the second subfamily contains 89 Streptomyces PPMs that
      lack the 5a and 5b catalytic domain motifs, similar to the PPMs SpoIIE and RsbU
      of Bacillus subtilis. Significant gene duplication was observed for the PPMs in
      the second subfamily. In addition, more than half (54 %) of the Streptomyces PPMs
      from the second subfamily were found to have at least one additional sensory
      domain, most commonly the PAS or the GAF domain. Phylogenetic analysis showed
      that these domains tended to be clustered according to the putative physiological
      functions rather than taxonomic relationship, implying that they might have
      arisen as a result of domain recruitment in a late evolutionary stage. This study
      provides an insight into how Streptomyces spp. may have expanded their PPM-based
      signal transduction networks to enable them to respond to a greater range of
      environmental changes.

PMID- 15583172
TI  - Genetic diversity among Pasteurella multocida strains of avian, bovine, ovine and
      porcine origin from England and Wales by comparative sequence analysis of the 16S
      rRNA gene.
AB  - Genetic diversity among 86 Pasteurella multocida isolates was investigated by
      comparative sequence analysis of a 1468 bp fragment of the 16S rRNA gene. The
      strains included 79 field isolates recovered from birds (poultry) (22), cattle
      (21), pigs (26) and sheep (10) within England and Wales, four Asian isolates
      associated with bovine haemorrhagic septicaemia, and the type strains of the
      three subspecies of P. multocida. Dulcitol and sorbitol fermentation patterns
      were also determined to establish correlations between subspecies status and
      phylogenetic relatedness. Nineteen 16S rRNA types were identified, but these were
      clustered into two distinct phylogenetic lineages, A and B. Sequences within
      lineages A and B had a mean number of nucleotide differences of 21.12+/-3.90.
      Isolates within lineage A were associated with birds, cattle, pigs and sheep,
      whereas those belonging to lineage B were recovered from birds and a cat. Eighty
      seven per cent of the isolates were classified as P. multocida subsp. multocida
      by dulcitol and sorbitol fermentation patterns, but these have diverse 16S rRNA
      gene sequences that were represented in both lineages A and B. Avian P. multocida
      subsp. septica isolates were associated exclusively with lineage B, but bovine P.
      multocida subsp. septica isolates were present in lineage A. P. multocida subsp.
      gallicida isolates of avian, bovine and porcine origin represent a homogeneous
      group within lineage A, but they have the same 16S rRNA type as certain P.
      multocida subsp. multocida isolates. These findings provide strong support for
      the view that dulcitol and sorbitol fermentation patterns are inaccurate
      indicators of genetic relatedness among P. multocida strains. Avian capsular type
      B isolates and capsular type B and E isolates associated with haemorrhagic
      septicaemia of cattle and water buffaloes are closely related and form a distinct
      cluster within lineage A. The current subspecies nomenclature of P. multocida
      neither accurately reflects the 16S rRNA-based phylogenetic relationships among
      isolates nor does it adequately encompass the full range of diversity within the
      species. The study provides a 16S rRNA-based evolutionary framework that will
      form the basis of further studies into the genetic diversity of P. multocida and
      will also help in the reclassification of the species.

PMID- 15583173
TI  - Protein FOG--a streptococcal inhibitor of neutrophil function.
AB  - Several strains of group G streptococci (GGS) form aggregates when grown in
      vitro. Aggregating strains interact with fibrinogen, and this study reports the
      isolation of a novel self-associating and fibrinogen-binding protein of GGS,
      denoted protein FOG. Sequencing of the fog gene revealed structural similarity
      with M proteins of both GGS and group A streptococci (GAS). Analogous to GAS, GGS
      were found to multiply in human blood. All strains of GGS express protein G, a
      protein known to interact with the constant region of immunoglobulin G and
      albumin. Surprisingly, a clinical isolate expressing protein G, but lacking
      protein FOG, was killed in human whole blood; however, the addition of intact
      soluble protein FOG restored the ability of the bacteria to survive and multiply
      in human blood. This is believed to be the first report of a soluble M-like
      protein salvaging an M-negative strain from being killed. The antibactericidal
      property of protein FOG is dependent on its fibrinogen-binding activity. Thus, in
      plasma, FOG precipitates fibrinogen, and when added to whole blood, protein FOG
      triggers the formation of visible aggregates comprising fibrinogen and
      neutrophils that are disabled in their killing of the bacteria. Moreover, the
      results emphasize the importance of an intact FOG molecule, as presented on the
      bacterial surface, for full protective effect.

PMID- 15583175
TI  - Acquired growth hormone deficiency and hypogonadotropic hypogonadism in a subject
      with repeated head trauma, or Tintin goes to the neurologist.

PMID- 15583176
TI  - Oh Christmas tree, oh Christmas tree ...

PMID- 15583177
TI  - Outbreak of neurologic syndrome and sequelae in 17 states and 2 provinces.

PMID- 15583178
TI  - A missed diagnosis.

PMID- 15583179
TI  - Referral request for S. Claus.

PMID- 15583180
TI  - Incidence of and risk factors for nodding off at scientific sessions.
AB  - We conducted a surreptitious, prospective, cohort study to explore how often
      physicians nod off during scientific meetings and to examine risk factors for
      nodding off. After counting the number of heads falling forward during 2 days of
      lectures, we calculated the incidence density curves for nodding-off episodes per
      lecture (NOELs) and assessed risk factors using logistic regression analysis. In
      this article we report our eye-opening results and suggest ways speakers can try
      to avoid losing their audience.

PMID- 15583181
TI  - The long and the short of it.

PMID- 15583182
TI  - Confronting the Christmas of our health care discontent.

PMID- 15583183
TI  - Excess in the pharmaceutical industry.

PMID- 15583184
TI  - How to read clinical journals: XII. How you too can profit from pharmaceutical
      advertisements.

PMID- 15583185
TI  - A view from the Internet age: let's build a health system that meets the needs of
      the next generation.

PMID- 15583186
TI  - Eating disorders and childhood obesity: who are the real gluttons?

PMID- 15583187
TI  - A survey of entertainment extremes among medical students in Croatia.

PMID- 15583188
TI  - The human genome project will not replace the physician.

PMID- 15583189
TI  - Wisdom from a medical elder.

PMID- 15583190
TI  - Darwinian pursuits with interruptions by Huxley: a brief pontification on medical
      education.

PMID- 15583191
TI  - Medical House blues.

PMID- 15583192
TI  - Tunnelling to 50: an exploratory medical memoir.

PMID- 15583193
TI  - House calls.

PMID- 15583194
TI  - Therapy in the gray zone: psychiatry recalled.

PMID- 15583196
TI  - The gift.

PMID- 15583197
TI  - How I got over the Christmas flu.

PMID- 15583198
TI  - References please.

PMID- 15583199
TI  - History's lessons.

PMID- 15583200
TI  - The discovery, elucidation, philosophical testing and formal proof of various
      exceptions to medical sayings and rules.

PMID- 15583201
TI  - Medical scientists and intimate relationships: translating the language of love.

PMID- 15583202
TI  - Cinderology: the Cinderella of academic medicine.

PMID- 15583203
TI  - Just a minute: incredible numbers at play at the macro and micro level.

PMID- 15583204
TI  - Impact of long-term political conflict on population health in Nepal.

PMID- 15583206
TI  - Skewed news 2004.

PMID- 15583207
TI  - MDs 'R' Us: gifts for your favourite specialist.

PMID- 15583209
TI  - Location, location, location! Ultrasound imaging in regional anaesthesia.

PMID- 15583210
TI  - Opioids and the neuroimmune axis.

PMID- 15583211
TI  - Difficulty in using ultrasonography for central venous cannulation in children:
      'a case of old dogs and new tricks'?

PMID- 15583212
TI  - Anaesthesia for spinal surgery in adults.

PMID- 15583214
TI  - Between Galen, Geddes, and the Gael: Arthur Brock, modernity, and medical
      humanism in early-twentieth-century Scotland.
AB  - Arthur Brock (1879-1947) is generally remembered as the physician who treated
      poet Wilfred Owen for shell shock and as the translator of Galen and other
      ancient physicians. He was also a key figure in the early-twentieth-century
      humanist revival within medicine. Brock's interest in humanism, I argue, was
      inspired by a broader concern about modernity and by a desire to return medicine
      and society to the more harmonious, organic existence that he believed was
      characteristic of ancient Greece and could still be found among "primitive"
      peoples, such as the Scottish Gaels. This article explores Brock's anxieties
      about modernity and its relations to his interests in ancient and "primitive"
      peoples; to his medical thought and practice; to his interests in history,
      sociology, language, and translation; and to his involvement in the social and
      political life of Edinburgh and North Queensferry, where he moved in 1925.
      Crucially, it shows how all these interests and activities were influenced by
      Brock's mentor, Edinburgh polymath Patrick Geddes. The article concludes with a
      discussion of Brock's place in early-twentieth-century medical humanism.

PMID- 15583215
TI  - Sewers in the city: a case study of individual-level mortality and public health
      initiatives in Northampton, Massachusetts, at the turn of the century.
AB  - Emerging industrial communities of nineteenth-century New England experienced
      both rapid population growth and lagging development of public health
      infrastructures. In turn, high mortality in these newly urban cities contributed
      to a delay in the regional mortality transition of the late nineteenth century.
      Analyzing death records and a file of linked cause-specific death and manuscript
      census records for the industrializing community of Northampton, Massachusetts,
      we show that early in the city's development, mortality clustered near industrial
      activities and open sewers. When industrial areas were sewered, clustering of
      mortality abated, and differences between industrial and commercial areas of the
      town were no longer significant. These findings illustrate Szreter's emphasis on
      considering both the benefits and costs of development. (1) Initial development
      contributed to high mortality in newly emergent urban-industrial centers like
      Northampton and was abated only when lagging public health infrastructures caught
      up with rapid growth and development near the turn of the century.

PMID- 15583216
TI  - The role of morbidity in the mortality decline of the nineteenth century:
      evidence from the military population at Gibraltar 1818-1899.
AB  - The causes of the nineteenth-century decline of mortality, characterized by lower
      mortality rates and increased longevity, have been the subject of debate among
      researchers for the past half-century. Because of a paucity of reliable data,
      little is understood about the role of morbidity, or illness episodes, in the
      mortality decline. This article introduces the results of a study that looks at
      the relationship of morbidity in the mortality decline during this portion of the
      epidemiological transition. The data are comprised of hospital admissions and
      deaths collected by the British army on the soldiers of the Gibraltar garrison
      from 1819 to 1899. Morbidity dropped during this period, but at a slower rate
      than mortality, and all categories of disease did not fall in concert; in some
      categories, morbidity rose as mortality dropped. Statistical modeling is used to
      analyze the categories of diseases that were most influential in the decline of
      mortality in this group. This research shows that there are discernible
      relationships between morbidity and mortality and that the two parameters are
      responding to different driving forces. Because changes within the military
      medical system may have had an effect on the relationship of the morbidity and
      mortality rates of the soldiers, surviving medical reports are used to
      reconstruct the medical care of the troops during the study period.

PMID- 15583217
TI  - Mechanism of hypertensive nephropathy in the Dahl/Rapp rat: a primary disorder of
      vascular smooth muscle.
AB  - The Dahl/Rapp salt-sensitive (S) rat is a model of salt-sensitive hypertension
      and hypertensive renal disease. This study explored the role of vascular
      remodeling in the development of renal failure in S rats. Groups of S and Sprague
      Dawley rats were given 0.3 and 8.0% NaCl diets for up to 21 days and evidence of
      smooth muscle proliferation identified using immunohistochemistry that showed
      nuclear accumulation of proliferating cell nuclear antigen and 5-bromo-2'-deoxy
      uridine. Compared with the other three groups, S rats on 8.0% NaCl diet showed
      increased nuclear labeling of cells of the aorta and arteries and arterioles of
      the kidney by the end of the first week of study. Progressive luminal narrowing
      of the interlobular arteries and preglomerular arterioles occurred in S rats over
      the 3 wk on the 8.0% NaCl diet. Accumulation of pimonidazole adducts and nuclear
      accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) were used as markers
      of tissue hypoxia. By the end of the second week of study, pimonidazole levels
      increased in S rats on 8.0% NaCl diet and deposition was apparent in tubular
      cells in the cortex and medulla. At the completion of the experiment, HIF-1alpha
      levels were increased in nuclear extracts from the cortex and medulla of S rats
      on this diet, compared with the other three groups of rats. The data demonstrated
      a disorder of the vascular remodeling process with proliferation of vascular
      smooth muscle cells temporally followed by development of tissue hypoxia in the
      hypertensive nephropathy of S rats on 8.0% NaCl diet.

PMID- 15583218
TI  - Hepatocyte growth factor induces an endothelin-mediated decline in glomerular
      filtration rate.
AB  - Hepatocyte growth factor (HGF) is a multifunctional cytokine that plays a crucial
      role in renal development, injury, and repair. HGF also serves a protective role
      in chronic renal disease by preventing tissue fibrosis. Endothelin-1 (ET-1),
      produced primarily by endothelial cells, is a potent vasoconstrictor that also
      acts as a proinflammatory peptide, promoting vascular injury and renal damage. In
      addition to mediating a variety of epithelial cell responses, HGF also induces
      hemodynamic changes that are poorly understood. The aim of the present study was
      to study the acute and chronic effects of HGF on ET-1 production in the kidney.
      We hypothesized that hemodynamic changes upon HGF treatment are likely mediated
      by immediate ET-1 release, whereas protection from renal fibrosis in rats
      chronically treated with HGF is likely due to suppression of ET-1 production.
      Acute HGF infusion into rats caused a decline in blood pressure that was enhanced
      by pretreatment with bosentan (an endothelin A and B receptor antagonist). HGF
      infusion also resulted in a decline in glomerular filtration rate (GFR) that
      could be entirely prevented by bosentan, suggesting that HGF acutely increases
      production and/or release of ET-1, which then mediates the observed decline in
      GFR. In cultured glomerular endothelial cells, HGF induced ET-1 production in a
      dose-dependent manner. Moreover, although there was an initial increase in ET-1
      production upon HGF treatment, longer administration suppressed ET-1 production.
      This finding was consistent with the observation in vivo of a decrease in ET-1
      production in renal parenchyma of rats chronically treated with HGF. Our data
      suggest both a hemodynamic and biological role for HGF-mediated ET-1 regulation.

PMID- 15583219
TI  - Summaries for patients. Sudden death in military recruits.

PMID- 15583220
TI  - Summaries for patients. Implantable cardioverter defibrillators and end-of-life
      care.

PMID- 15583221
TI  - Summaries for patients. Diagnosis of suspected recurrent deep venous thrombosis
      using D-dimer and compression ultrasonography.

PMID- 15583222
TI  - Summaries for patients. Sleep duration and levels of hormones that influence
      hunger.

PMID- 15583223
TI  - Sudden death in young adults: a 25-year review of autopsies in military recruits.
AB  - BACKGROUND: Sudden death among military recruits is a rare but devastating
      occurrence. Because extensive medical data are available on this cross-sectional
      and diverse population, identification of the underlying causes of sudden death
      may promote health care policy to reduce the incidence of sudden death.
      OBJECTIVE: To determine the causes of nontraumatic sudden death among a cohort of
      military recruits. DESIGN: Retrospective cohort study using demographic and
      autopsy data from the Department of Defense Recruit Mortality Registry. SETTING:
      Basic military training. PATIENTS: All nontraumatic sudden deaths from a
      monitored 6.3 million men and women age 18 to 35 years. MEASUREMENTS: Descriptive
      analysis, crude mortality rates of causes of sudden death, and frequency of
      events as a function of cause of death. RESULTS: Of 126 nontraumatic sudden
      deaths (rate, 13.0/100,000 recruit-years), 108 (86%) were related to exercise.
      The most common cause of sudden death was an identifiable cardiac abnormality (64
      of 126 recruits [51%]); however, a substantial number of deaths remained
      unexplained (44 of 126 recruits [35%]). The predominant structural cardiac
      abnormalities were coronary artery abnormalities (39 of 64 recruits [61%]),
      myocarditis (13 of 64 recruits [20%]), and hypertrophic cardiomyopathy (8 of 64
      recruits [13%]). An anomalous coronary artery accounted for one third (21 of 64
      recruits) of the cases in this cohort, and, in each, the left coronary artery
      arose from the right (anterior) sinus of Valsalva, coursing between the pulmonary
      artery and aorta. LIMITATIONS: This cohort underwent a preenlistment screening
      program that included history and physical examination; this may have altered
      outcomes. CONCLUSIONS: Cardiac abnormalities are the leading identifiable cause
      of sudden death among military recruits; however, more than one third of sudden
      deaths remain unexplained after detailed medical investigation.

PMID- 15583224
TI  - Management of implantable cardioverter defibrillators in end-of-life care.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICDs) can prevent premature
      death from an arrhythmia but may also prolong the dying process and make it more
      distressing. OBJECTIVE: To describe the frequency, timing, and correlates of
      discussions about deactivating ICDs. DESIGN: Retrospective cohort study. SETTING:
      Telephone survey. PARTICIPANTS: Next of kin of patients with ICDs who died of any
      cause. Of 136 next of kin contacted, 100 (74%) participated. MEASUREMENTS:
      Incidence of discussions about deactivating ICDs and timing of last shock from
      ICD. RESULTS: Next of kin reported that clinicians discussed deactivating the ICD
      in only 27 of the 100 cases. Most discussions occurred in the last few days of
      life. Family members reported that 8 patients received a shock from their ICD in
      the minutes before death. LIMITATIONS: This retrospective survey relied on the
      reports of next of kin. CONCLUSIONS: Next of kin reported that clinicians
      discussed deactivating ICDs with few patients. Individuals who choose to receive
      this device should have the opportunity to choose to discontinue it as death
      approaches.

PMID- 15583225
TI  - Negative D-dimer result to exclude recurrent deep venous thrombosis: a management
      trial.
AB  - BACKGROUND: All of the available diagnostic tests for deep venous thrombosis
      (DVT) have limitations for excluding acute recurrent DVT. Measurement of plasma d
      dimer by using an automated quantitative assay may be useful as a rapid exclusion
      test in patients with suspected recurrent DVT. OBJECTIVE: To test the safety of
      withholding additional diagnostic testing and heparin treatment in patients who
      have a negative d-dimer result at presentation (using the automated quantitative
      assay STA-Liatest D-di), regardless of their symptoms. DESIGN: Prospective cohort
      study. SETTING: Academic medical center in the United States. PATIENTS: 300
      consecutive patients with suspected recurrent DVT. INTERVENTION: Patients
      underwent d-dimer testing at presentation. In patients with negative D-dimer
      results, heparin therapy was withheld, and no further diagnostic testing for DVT
      was done as part of the initial evaluation. Patients with positive D-dimer
      results underwent compression ultrasonography. MEASUREMENTS: The primary outcome
      measure was a diagnosis of new symptomatic venous thromboembolism confirmed by
      diagnostic testing during the 3-month follow-up period. RESULTS: Of the 300 study
      patients, the d-dimer result was negative at presentation in 134 patients (45%;
      negative cohort) and positive at presentation in 166 patients. Of the 166
      patients, compression ultrasonography documented new DVT in 54 patients.
      Compression ultrasonography findings were normal in 79 patients and were
      inconclusive in 33 patients. After 3 months of follow-up, 1 of 134 patients in
      the negative cohort had confirmed venous thromboembolism (0.75% [95% CI, 0.02% to
      4.09%]). Venous thromboembolism on follow-up could not be definitively excluded
      in 5 patients with recurrent leg symptoms and in 1 patient who died. If these
      patients are considered to have venous thromboembolism, the incidence during the
      3-month follow-up period would be 6.0% (CI, 2.6% to 11.4%) (8 of 134 patients).
      LIMITATIONS: There is no accepted diagnostic reference standard for recurrent
      DVT. The precision of the estimate of the incidence of venous thromboembolism on
      follow-up and the generalizability to settings other than an academic health
      center should be evaluated. CONCLUSIONS: Measurement of plasma d-dimer by using
      the automated quantitative assay STA-Liatest D-di seems to provide a simple
      method for excluding acute recurrent DVT in symptomatic patients.

PMID- 15583226
TI  - Brief communication: Sleep curtailment in healthy young men is associated with
      decreased leptin levels, elevated ghrelin levels, and increased hunger and
      appetite.
AB  - BACKGROUND: Total sleep deprivation in rodents and in humans has been associated
      with hyperphagia. Over the past 40 years, self-reported sleep duration in the
      United States has decreased by almost 2 hours. OBJECTIVE: To determine whether
      partial sleep curtailment, an increasingly prevalent behavior, alters appetite
      regulation. DESIGN: Randomized, 2-period, 2-condition crossover clinical study.
      SETTING: Clinical Research Center, University of Chicago, Chicago, Illinois.
      PATIENTS: 12 healthy men (mean age [+/-SD], 22 +/- 2 years; mean body mass index
      [+/-SD], 23.6 +/- 2.0 kg/m2). MEASUREMENTS: Daytime profiles of plasma leptin and
      ghrelin levels and subjective ratings of hunger and appetite. INTERVENTION: 2
      days of sleep restriction and 2 days of sleep extension under controlled
      conditions of caloric intake and physical activity. RESULTS: Sleep restriction
      was associated with average reductions in the anorexigenic hormone leptin
      (decrease, 18%; P = 0.04), elevations in the orexigenic factor ghrelin (increase,
      28%; P < 0.04), and increased hunger (increase, 24%; P < 0.01) and appetite
      (increase, 23%; P = 0.01), especially for calorie-dense foods with high
      carbohydrate content (increase, 33% to 45%; P = 0.02). LIMITATIONS: The study
      included only 12 young men and did not measure energy expenditure. CONCLUSIONS:
      Short sleep duration in young, healthy men is associated with decreased leptin
      levels, increased ghrelin levels, and increased hunger and appetite.

PMID- 15583227
TI  - Systematic review: effects of resident work hours on patient safety.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      mandated new work hours rules for all residency programs in July 2003. PURPOSE:
      To critically evaluate the evidence that adhering to the ACGME standards will
      improve patient safety. DATA SOURCES: Searches of electronic databases (MEDLINE,
      EMBASE, PREMEDLINE, and Current Contents) and other methods to identify the
      English-language literature for studies on resident work hours for the years 1966
      to 2004. STUDY SELECTION: Studies that assessed a system change designed to
      counteract the effects of work hours, fatigue, or sleep deprivation and that
      included an outcome related to patient safety were included. Seven studies met
      these criteria. DATA EXTRACTION: Two investigators abstracted data from all
      included studies by using a standard data abstraction form; each study was rated
      according to established criteria to assess study design quality. DATA SYNTHESIS:
      Interventions used were float systems, other cross-coverage systems, or
      unspecified schedule changes. Outcomes included mortality, adverse events, and
      medication errors. The results suggest that introducing such interventions has an
      unclear effect on selected patient safety indicators. Specifically, some
      indicators (such as mortality) may not change after interventions, while other
      indicators may improve or worsen. LIMITATIONS: This analysis is limited by the
      study designs of the included studies, the diversity of interventions in the
      studies, and the possibility of publication bias favoring studies that
      demonstrated statistically significant differences. CONCLUSION: Evidence on
      patient safety is insufficient to inform the process of reducing resident work
      hours.

PMID- 15583228
TI  - Systematic review: transient left ventricular apical ballooning: a syndrome that
      mimics ST-segment elevation myocardial infarction.
AB  - The transient left ventricular apical ballooning syndrome, also known as
      takotsubo cardiomyopathy, is characterized by transient wall-motion abnormalities
      involving the left ventricular apex and mid-ventricle in the absence of
      obstructive epicardial coronary disease. In this paper, we review case series
      that report on patients with the transient left ventricular apical ballooning
      syndrome to better characterize patients presenting with the syndrome. We
      identified 7 case series that reported on at least 5 consecutive patients with
      the transient left ventricular apical ballooning syndrome. The syndrome more
      often affects postmenopausal women (82% to 100%) (mean age, 62 to 75 years).
      Patients commonly present with ST-segment elevation in the precordial leads,
      chest pain, relatively minor elevation of cardiac enzyme and biomarker levels,
      and transient apical systolic left ventricular dysfunction despite the absence of
      obstructive epicardial coronary disease. An episode of emotional or physiologic
      stress frequently precedes presentation with the syndrome. The in-hospital
      mortality rate seems to be low, as does the risk for recurrence.

PMID- 15583229
TI  - Meta-analysis: outcomes in patients with suspected pulmonary embolism managed
      with computed tomographic pulmonary angiography.
AB  - BACKGROUND: Spiral computed tomographic pulmonary angiography (CTPA) is
      increasingly being used in the evaluation of patients with clinically suspected
      pulmonary embolism (PE). However, CTPA as a definitive diagnostic test may be
      limited by inadequate sensitivity, especially in instances of isolated
      subsegmental emboli. PURPOSE: To assess the safety of withholding anticoagulation
      in patients with suspected PE and negative results on CTPA. DATA SOURCES: All
      relevant studies identified in MEDLINE (1966 to March 2004) and EMBASE (1974 to
      2004) and in bibliographies of key articles. The search was not limited to the
      English language. STUDY SELECTION: The authors selected all published studies
      that used CTPA to evaluate suspected PE and reported at least 3 months of follow
      up in patients not receiving anticoagulation on the basis of a negative CTPA
      result. DATA EXTRACTION: Two reviewers independently rated study quality on the
      basis of predetermined criteria. Data were extracted on participants, CTPA
      technique, diagnostic studies performed, prevalence of PE, number of patients
      with negative or indeterminate CTPA results who were followed, and subsequent
      rates of venous thromboembolism and fatal PE. DATA SYNTHESIS: Twenty-three
      studies reported on 4657 patients with negative CTPA results who did not receive
      anticoagulation. The 3-month rate of subsequent venous thromboembolic events was
      1.4% (95% CI, 1.1% to 1.8%), and the 3-month rate of fatal PE was 0.51% (CI,
      0.33% to 0.76%). LIMITATIONS: The CTPA technology used varied across studies and
      was not applied uniformly in the same step of diagnostic algorithms. Only 1 study
      used CTPA as the sole diagnostic test. CONCLUSION: The rate of subsequent venous
      thromboembolism after negative results on CTPA is similar to that seen after
      negative results on conventional pulmonary angiography. It appears to be safe to
      withhold anticoagulation after negative CTPA results.

PMID- 15583230
TI  - Update in infectious diseases.

PMID- 15583231
TI  - Sudden cardiac death in young military recruits: guarding the heart of a soldier.

PMID- 15583232
TI  - A good night's sleep: future antidote to the obesity epidemic?

PMID- 15583233
TI  - A rose for Dr. Martin.

PMID- 15583234
TI  - Single complete compression ultrasonography for suspected deep venous thrombosis:
      ideal in routine clinical practice?

PMID- 15583235
TI  - Obstetricians still wanted: mothers should read the fine print.

PMID- 15583236
TI  - Aerobic physical exercise and atherosclerosis in men.

PMID- 15583237
TI  - Foreign medicine.

PMID- 15583238
TI  - Exercise and atherosclerosis.

PMID- 15583239
TI  - Dose effects of steroids on survival in sepsis.

PMID- 15583240
TI  - Dose effects of steroids on survival in sepsis.

PMID- 15583241
TI  - Management of the acute radiation syndrome.

PMID- 15583242
TI  - Ginseng and warfarin interactions.

PMID- 15583243
TI  - Angiotensin-converting enzyme inhibitors and diuretics: optimal combination
      therapy.

PMID- 15583244
TI  - B-type natriuretic peptide is effective therapy before care.

PMID- 15583245
TI  - Multiple pseudotumors in IgG4-associated multifocal systemic fibrosis.

PMID- 15583246
TI  - The Health Insurance Portability and Accountability Act and the informed consent
      process.

PMID- 15583247
TI  - Gastrointestinal beriberi: a previously unrecognized syndrome.

PMID- 15583248
TI  - Injury control in South America: the art and science of disentanglement.

PMID- 15583249
TI  - Evidence based advocacy.

PMID- 15583251
TI  - Injury questions on household surveys from around the world.

PMID- 15583252
TI  - Reflections on the highway safety field.

PMID- 15583253
TI  - Cochrane injuries group.

PMID- 15583254
TI  - Child and family safety device affordability by country income level: an 18
      country comparison.
AB  - OBJECTIVE: To compare availability, urban price, and affordability of
      child/family safety devices between 18 economically diverse countries. DESIGN:
      Descriptive: urban price surveys by local safety organisations or shoppers.
      SETTING: Retail stores and internet vendors. MAIN OUTCOME MEASURES: Prices
      expressed in US dollars, and affordability measured by hours of factory work
      needed to buy a child safety seat, a belt-positioning booster seat, a child
      bicycle helmet, and a smoke alarm. RESULTS: Prices of child and family safety
      devices varied widely between countries but the variation for child safety seats
      and bicycle helmets did not relate strongly to country income. Safety devices
      were expensive, often prohibitively so, in lower income countries. Far more hours
      of factory work were required to earn a child safety device in lower income than
      middle income, and middle income than higher income, countries. A bicycle helmet,
      for example, cost 10 hours of factory work in lower income countries but less
      than an hour in higher income countries. Smoke alarms and booster seats were not
      available in many lower income countries. CONCLUSIONS: Bicycles and two-axle
      motor vehicles were numerous in lower and middle income countries, but
      corresponding child safety devices were often unaffordable and sometimes not
      readily available. The apparent market distortions and their causes merit
      investigation. Advocacy, social marketing, local device production, lowering of
      tariffs, and mandatory use legislation might stimulate market growth. Arguably, a
      moral obligation exists to offer subsidies that give all children a fair chance
      of surviving to adulthood.

PMID- 15583255
TI  - Compliance with external hip protectors in nursing homes in Norway.
AB  - OBJECTIVES: To investigate compliance with hip protector use. DESIGN:
      Observational prospective study. SETTING: 19 nursing homes (1040 beds). SUBJECTS:
      All residents during an 18 month period were included in this study.
      INTERVENTION: Hip protectors were introduced as a regular part of health care
      service for all residents. Residents at high risk were encouraged to use hip
      protectors regularly. Each nursing home had a contact person. MAIN OUTCOME
      MEASURES: The percentage of residents accepting the hip protector offer,
      probability of continued use, reasons for terminating use, and percentage of
      falls with hip protector were evaluated. RESULTS: Fifty five percent of the
      residents accepted the hip protector offer. The percentage increased by age, but
      showed no significant dependence on gender, profession of the contact person, or
      size of nursing home. The probability of continued use showed no significant
      dependence on age and gender. Nursing homes with a nurse as contact person showed
      51% higher risk of residents terminating regular hip protector use than nursing
      homes with a physiotherapist as contact person (relative risk (RR) 1.51, 95%
      confidence interval (CI) 1.11 to 2.05, p = 0.008). The corresponding result for
      large (75-92 beds) compared with small (24-68 beds) nursing homes was RR = 1.44
      (95% CI 1.02 to 2.02, p = 0.036). Seventy six percent of 2323 falls occurred
      while using hip protectors. CONCLUSION: The contact person and size of the
      nursing home seemed to be important factors for continued use of hip protectors
      while age and gender seemed to be less important.

PMID- 15583256
TI  - Evaluation of the North American Guidelines for Children's Agricultural Tasks
      using a case series of injuries.
AB  - OBJECTIVE: To evaluate the potential for the North American Guidelines for
      Children's Agricultural Tasks (NAGCAT) to prevent the occurrence of pediatric
      farm injuries. This evaluation focuses upon farm injuries experienced when
      children were engaged in farm work. DESIGN: Novel outcome evaluation involving
      primary review of three retrospective case series. SETTING: Fatal, hospitalized,
      and restricted activity injuries from the United States and Canada. SUBJECTS:
      Nine hundred and thirty four pediatric farm injury cases. METHODS: The
      applicability of NAGCAT to each case was rated. For injuries where NAGCAT were
      applicable, recurrent injury patterns were described and the potential for NAGCAT
      to prevent their occurrence was assessed. RESULTS: A total of 283 (30.3%) cases
      involved children engaged in farm work. There was an applicable NAGCAT guideline
      in 64.9% of the work related cases. Leading individual guidelines applicable to
      the injury events were: (1) working with large animals; (2) driving a farm
      tractor; and (3) farm work with an all-terrain vehicle. In the judgment of the
      research team, 59.6% of these injuries were totally preventable if the principles
      espoused by NAGCAT had been applied. CONCLUSIONS: NAGCAT are a set of consensus
      guidelines aimed at the prevention of pediatric farm injuries. The findings
      suggest that NAGCAT, if applied, would be efficacious in preventing many of the
      most serious injuries experienced by children engaged in farm work. However, work
      related injuries represent only a modest portion of pediatric farm injuries. This
      new information assists in the refinement of NAGCAT as an injury control resource
      and puts its potential efficacy into context.

PMID- 15583257
TI  - Prevalence and diffusion of helmet use at ski areas in Western North America in
      2001-02.
AB  - OBJECTIVE: The purpose of this study was to examine diffusion of and predictors
      of helmet use among skiers and snowboarders in the Western United States and
      Canada. DESIGN: 6400 skiers and snowboarders at 29 ski resorts in the Western
      United States and Canada were interviewed on chair lifts and observed for helmet
      use during two consecutive ski seasons (winters 2001 and 2002). SETTING: Skiers
      and snowboarders were observed and interviewed at 29 ski resorts in Alaska,
      California, Colorado, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, and
      British Columbia as part of a sun protection project. SUBJECTS: Participants
      completing the survey consisted of 3525 adult skiers and snowboarders in the 2002
      season and 2978 adult skiers and snowboarders in the 2001 season. MAIN OUTCOME
      MEASURE: The outcome measure for all analyses was prevalence of helmet use by
      skiers and snowboarders. RESULTS: Helmet use by skiers and snowboarders is
      increasing and is most prevalent among snowboarders, experts, and more frequent
      skiers/snowboarders. No evidence was found for the hypothesis that helmet use is
      diffusing more rapidly among earlier adopters of helmets than later adopters.
      CONCLUSIONS: Although controversy remains, helmets are rapidly diffusing as a
      safety device at western North American ski resorts. Expert and more frequent
      skiers and snowboarders are more likely to wear helmets, which may indicate that
      helmets are recognized as a safety device.

PMID- 15583258
TI  - Risk of injury for occupants of motor vehicle collisions from unbelted occupants.
AB  - OBJECTIVE: Unbelted occupants may increase the risk of injury for other occupants
      in a motor vehicle collision (MVC). This study evaluated the association between
      occupant restraint use and the risk of injury (including death) to other vehicle
      occupants. DESIGN: A population based cohort study. SETTING: United States.
      SUBJECTS: MVC occupants (n = 152 191 unweighted, n = 18 426 684 weighted) seated
      between a belted or unbelted occupant and the line of the principal direction of
      force in frontal, lateral, and rear MVCs were sampled from the 1991-2002 National
      Automotive Sampling System General Estimates System. Offset MVCs were not
      included in the study. MAIN OUTCOME MEASURE: Risk ratios and 95% confidence
      intervals for injury (including death) for occupants seated contiguous to
      unbelted occupants compared to occupants seated contiguous to belted occupants.
      Risk ratios were adjusted for at risk occupant's sex, age, seating position,
      vehicle type, collision type, travel speed, crash severity, and at risk
      occupants' own seat belt use. RESULTS: Exposure to unbelted occupants was
      associated with a 40% increased risk of any injury. Belted at risk occupants were
      at a 90% increased risk of injury but unbelted occupants were not at increased
      risk. Risks were similar for non-incapacitating and capacitating injuries. There
      was a 4.8-fold increased risk of death for exposed belted occupants but no
      increased risk of death for unbelted occupants. CONCLUSIONS: Belted occupants are
      at an increased risk of injury and death in the event of a MVC from unbelted
      occupants.

PMID- 15583259
TI  - Epidemiology of lower limb fractures in general practice in the United Kingdom.
AB  - STUDY OBJECTIVE: To estimate the incidence of lower limb fractures in the United
      Kingdom and assess the relative importance of various risk factors for lower limb
      fractures. DESIGN: Cohort analysis and matched case-control study. SETTING:
      General practices contributing information to the General Practice Research
      Database. SUBJECTS: Individuals registered with these general practices who were
      at risk for a first time lower limb fracture from 1 January 1990 to 31 December
      2001. MAIN OUTCOME MEASURES: Age, sex, and fracture site specific incidence
      rates; relative risks and population attributable risks for various medical risk
      factors. RESULTS: Overall, the risk of lower limb fracture was 17% higher in
      women then in men. Within age groups, men and women had generally similar
      proportions of fractures at specific sites in the lower limb. Among the risk
      factors evaluated, road collisions were associated with the highest relative risk
      for lower limb fracture, but only accounted for 3.1% or less of the population
      attributable risk for specific fracture types in any age group. The relative risk
      for lower limb fracture associated with a diagnosis of dementia was 2.3 (95%
      confidence interval 2.0 to 2.6), while relative risk estimates for other medical
      diagnoses were less than 2. Fracture risk was increased among current users of
      corticosteroids, antipsychotics, antidepressants, and hypnotic/sedatives, but the
      population attributable risks for each of these drug classes within fracture and
      age specific strata were only 3.0% or less. CONCLUSIONS: Many risk factors for
      lower limb fracture have been identified, but population attributable risk
      estimates for various risk factors are small. These findings suggest that
      multifactorial prevention programs are needed to decrease the incidence of lower
      limb fractures in the general population.

PMID- 15583260
TI  - Engagement in safety practices to prevent home injuries in preschool children
      among white and non-white ethnic minority families.
AB  - OBJECTIVE: To examine engagement in home safety practices to prevent injuries in
      preschool children among white and non-white ethnic minority families. DESIGN: A
      self completion postal questionnaire assessed sociodemographic characteristics
      and engagement in home safety practices. SETTING: Deprived areas in the city of
      Nottingham, United Kingdom. SUBJECTS: 3906 caregivers of children aged under 5
      years. MAIN OUTCOME MEASURES: Use of fireguards, stair gates, smoke alarms,
      window locks and safe storage of medicines, sharp objects, and cleaning products.
      RESULTS: Of the 3906 families, 3805 gave their ethnic origin of which 16.5%
      classed themselves as from a non-white ethnic minority. The safety practices most
      commonly adopted by respondents were safe storage of medicines (87.9%) and use of
      smoke alarms (72.3%). Respondents from non-white ethnic minorities were
      significantly less likely to adopt all safety practices except they were less
      likely than whites to store sharp objects unsafely (odds ratio (OR) 0.68, 95%
      confidence interval (CI) 0.56 to 0.84). Those from non-white ethnic minorities
      were significantly more likely to indicate that they "did not know they could
      get" fireguards (adjusted OR 6.01, 95% CI 2.64 to 13.65), stair gates (adjusted
      OR 4.47, 95% CI 1.53 to 13.05), and cupboard locks (adjusted OR 3.96, 95% CI 2.77
      to 5.66) than whites. They were also significantly more likely to say they would
      need help fitting fireguards (adjusted OR 1.98, 95% CI 1.03 to 3.81), stair gates
      (adjusted OR 3.61, 95% CI 2.11 to 6.17), and cupboard locks (adjusted OR 1.88,
      95% CI 1.39 to 2.54). CONCLUSIONS: Our results support the hypothesis that
      families from non-white ethnic minorities are less likely to engage in some
      safety practices and illustrate inequalities in access to information regarding
      the availability and fitting of safety equipment. Further work is required to
      examine the association between adoption of safety practices and injury rates in
      children from non-white ethnic minorities.

PMID- 15583261
TI  - Diagnosis based injury severity scaling: investigation of a method using
      Australian and New Zealand hospitalisations.
AB  - OBJECTIVE: To assess the performance of the International Classification of
      Diseases (ICD) based injury severity score, ICISS, when applied to two versions
      of the 10th edition of ICD, ICD-10 and ICD-10-AM. DESIGN: ICISS was assessed on
      its ability to predict threat to life using logistic regression modelling. Models
      used ICISS and age as predictors and survival as the outcome. SETTING: Australia
      and New Zealand. Patients or SUBJECTS: Hospitalisations with an ICD-10-AM
      principal diagnosis in the range S00-T89 from 1 July 1999 to 30 June 2001
      (Australia) or 1 July 1999 to 31 December 2001 (New Zealand). INTERVENTIONS:
      None. MAIN OUTCOME MEASURES: The models were assessed in terms of their
      discrimination, measured by the concordance score, and calibration, measured
      using calibration curves and the Hosmer-Lemeshow statistic. RESULTS: 523 633
      Australian and 124 767 New Zealand hospitalisations were selected, including 7230
      and 1565 deaths respectively. Discrimination was high in all the fitted models
      with concordance scores of 0.885 to 0.910. Calibration results were also
      promising with all calibration curves being close to linear, though ICISS
      appeared to underestimate mortality somewhat for cases with an ICISS score less
      than 0.6. Overall ICISS performed better when applied to the Australian than the
      New Zealand hospitalisations. Australian and New Zealand hospitalisations were
      very similar. ICISS was also only a little more successful when ICD-10-AM rather
      than mapped ICD-10 was used. CONCLUSIONS: ICISS appears to be a reasonable way to
      estimate severity for databases using ICD-10 or ICD-10-AM. It is also likely to
      work well for other clinical variants of ICD-10.

PMID- 15583262
TI  - Genetic bases of the rifampin resistance phenotype in Brucella spp.
AB  - Rifampin is one of the most potent and broad-spectrum antibiotics against
      bacterial pathogens. Its bactericidal activity is due to its ability to bind to
      the beta subunit of the DNA-dependent RNA polymerase encoded by the rpoB gene.
      Mutations of the rpoB gene have been characterized in rifampin-resistant (Rif(r))
      strains of Escherichia coli and Mycobacterium tuberculosis. The genetic bases of
      Rif(r) in Brucella spp. are still unknown. In the present study, the nucleotide
      sequences of the rpoB gene of the Rif(r) vaccine strain Brucella abortus RB51 and
      of 20 Rif(r) clones derived in our laboratory from two Brucella melitensis
      isolates were determined. These sequences were then compared to those of the
      respective rifampin-susceptible (Rif(s)) parental strains and to the published B.
      melitensis strain 16M. All Rif(r) strains carried one or more missense mutations
      mapping in two regions of the rpoB gene. These two "hot" regions were
      investigated in eight additional Rif(r) Brucella laboratory mutants and in 20
      reference Rif(s) Brucella strains. rpoB mutations were found in all Rif(r)
      mutants. In contrast, no missense mutations were found in any analyzed Rif(s)
      strains. Our results represent the first from a study of the molecular
      characterization of rpoB mutations in resistant Brucella strains and provide an
      additional proof of the association of specific rpoB mutations with the
      development of the Rif(r) phenotype in prokaryotes. In addition, because of the
      relationship between Rif(r) and the attenuation of virulence in Brucella spp.,
      studies of virulence in these mutants may provide useful information about the
      genetic basis of pathogenesis in Brucella.

PMID- 15583263
TI  - Heterogeneity among virulence and antimicrobial resistance gene profiles of
      extraintestinal Escherichia coli isolates of animal and human origin.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) isolates collected from
      different infected animals and from human patients with extraintestinal
      infections in 2001 were characterized for their phenotypic and genotypic
      antimicrobial resistance profiles, genotypes, and key virulence factors. Among
      the 10 antimicrobial agents tested, resistance to ampicillin, tetracycline, and
      sulfonamides was most frequent. Multiresistant strains were found in both the
      animal and the human groups of isolates. Resistance gene distribution was
      assessed by colony hybridization. Similar antibiotic resistance patterns could be
      observed in the animal and the human isolates. Although some resistance genes,
      such as bla(TEM), sulI, and sulII, were equally represented in the animal and
      human ExPEC isolates, differences in the distributions of tetracycline [tet(D)],
      chloramphenicol (catI, catIII, and floR), and trimethoprim (dhfrI, dhfrV,
      dhfrVII, and dhfrXIII) resistance genes were observed between the animal and the
      human isolates. Approximately one-third of the ExPEC isolates possessed a class 1
      integron. The four major different variable regions of the class 1 integron
      contained aminoglycoside (aadA1, aadA2, aadA5, and aadA6) and/or trimethoprim
      (dhfrIb, dhfrXII, and dhfrXVII) resistance genes. The ExPEC strains belonged to
      different phylogenetic groups, depending on their host origin. Strains isolated
      from animal tissues belonged to either a commensal group (group A or B1) or a
      virulent group (group B2 or D), while the majority of the human isolates belonged
      to a virulent group (group B2 or D). Although the limited number of isolates
      evaluated in the present study prevents firm epidemiological conclusions from
      being made, on a more global scale, these data demonstrate that extraintestinal
      isolates of E. coli can possess relatively distinct intra- and intergroup
      resistance gene profiles, with animal isolates presenting a more heterogeneous
      group than human isolates.

PMID- 15583264
TI  - Antigenic divergence suggested by correlation between antigenic variation and
      pulsed-field gel electrophoresis profiles of Bordetella pertussis isolates in
      Japan.
AB  - Antigenic divergence has been found between Bordetella pertussis vaccine strains
      and circulating strains in several countries. In the present study, we analyzed
      B. pertussis isolates collected in Japan from 1988 to 2001 using pulsed-field gel
      electrophoresis (PFGE) and sequencing of two virulence-associated proteins. The
      107 isolates were classified into three major groups by PFGE analysis; 87 (81%)
      were type A, 19 (18%) were type B, and 1 (1%) was type C. Sequence analysis of
      the S1 subunit of pertussis toxin (ptxS1) and adhesion pertactin (prn) genes
      revealed the presence of two (ptxS1A and ptxS1B) and three (prn1, prn2, and prn3)
      variants, respectively, in the isolates. Among those isolates, 82 (95%) of the 87
      type A strains and the type C strain had the same combination of ptxS1B and prn1
      alleles (ptxS1B/prn1) as the Japanese vaccine strain. On the other hand, 17 (90%)
      of 19 type B strains had an allele (ptxS1A/prn2) distinct from that of the
      vaccine strain. A correlation was found between the antigenic variation and the
      PFGE profile in the isolates. In addition, the frequency of the type B strain was
      0, 27, 0, 42, and 37% of the isolates in the periods 1988 to 1993, 1994 to 1995,
      1996 to 1997, 1998 to 1999, and 2000 to 2001, respectively. In contrast, the
      number of reported pertussis-like and pertussis cases decreased gradually from
      1991 on, suggesting that the antigenic divergence did not affect the efficacy of
      pertussis vaccination in Japan.

PMID- 15583265
TI  - Diagnosis of schistosomiasis by reagent strip test for detection of circulating
      cathodic antigen.
AB  - A newly developed reagent strip assay for the diagnosis of schistosomiasis based
      on parasite antigen detection in urine of infected individuals was evaluated. The
      test uses the principle of lateral flow through a nitrocellulose strip of the
      sample mixed with a colloidal carbon conjugate of a monoclonal antibody specific
      for Schistosoma circulating cathodic antigen (CCA). The strip assay to diagnose a
      group of highly infected schoolchildren in Mwanza, Tanzania, demonstrated a high
      sensitivity and association with the intensity of infection as measured both by
      egg counts, and by circulating anodic antigen and CCA levels determined by enzyme
      linked immunosorbent assay. A specificity of ca. 90% was shown in a group of
      schistosome-negative schoolchildren from Tarime, Tanzania, an area where
      schistosomiasis is not endemic. The test is easy to perform and requires no
      technical equipment or special training. The stability of the strips and the
      conjugate in the dry format lasts for at least 3 months at ambient temperature in
      sealed packages, making it suitable for transport and use in areas where
      schistosomiasis is endemic. This assay can easily be developed to an end-user
      format.

PMID- 15583266
TI  - Development of a rapid PCR method using the insertion sequence IS1203 for
      genotyping Shiga toxin-producing Escherichia coli O157.
AB  - We developed a rapid PCR method utilizing the diversity of the insertion site
      IS1203 for genotyping Shiga toxin-producing Escherichia coli (STEC) O157 (IS1203
      PCR typing). DNA fragments digested by PvuII, which cut IS1203 at one site, were
      ligated with themselves and detected by PCR with outward-facing primer pairs for
      IS1203. To minimize nonspecific bands, nested PCR was also performed. Two
      fingerprinting patterns produced from the upstream or downstream regions of
      IS1203 were obtained within 1 or 2 days. By combining the two patterns, 79 STEC
      O157 isolates were classified into 39 types, which were then classified into 36
      subtypes by pulsed-field gel electrophoresis (PFGE). The discriminatory power of
      IS1203 PCR typing (D = 0.974) is similar to that of PFGE (D = 0.981). This method
      can be used for rapid and simplified genotyping.

PMID- 15583267
TI  - Analysis of Trichosporon isolates obtained from the houses of patients with
      summer-type hypersensitivity pneumonitis.
AB  - Summer-type hypersensitivity pneumonitis (SHP) is type III or IV allergies
      developed by repeated inhalation of arthroconidia of Trichosporon species. We
      identified 105 strains obtained from the homes of 36 SHP patients by analysis of
      the intergenic spacer (IGS) 1 region, which is located between the 26S and 5S
      rRNA genes; in addition, we analyzed the IGS genotypes of the strains.
      Serologically, Trichosporon species are classified as serotype I, II, III, or I
      III. Of the 105 strains, 43 (41.1%), 53 (50.5%), and 9 (8.6%) strains were
      isolated as serotypes I, II, and III, respectively. Serotype I, II, and III
      strains were recovered from 19 (52.8%), 29 (80.6%), and 4 (11.1%) of the 36
      houses of SHP patients, respectively. No serotype I-III strains were isolated
      from the houses. Of 43 serotype I strains, 42 (97.7%) were identified as
      Trichosporon dermatis, and the remaining one was T. terricola. Of 53 serotype II
      strains, 37 (69.8%) were identified as T. asahii, and the remaining serotype II
      isolates were T. aquatile (1.9%), T. coremiiforme (7.5%), T. faecale (1.9%), T.
      japonicum (15.1%), and T. ovoides (3.8%). There were nine serotype III strains
      comprised of T. montevideense (77.8%) and T. domesticum (22.2%). Intraspecies
      diversity was found only in T. asahii. This microorganism also causes
      opportunistic infections (trichosporonosis); seven genotypes of its IGS 1 region
      have been identified. While the strains of T. asahii obtained from Japanese
      patients with trichosporonosis were genotype I, the strains from the houses of
      SHP patients were genotype III. Based on our analysis, we conclude that the
      strains that play the most significant roles in the development of SHP are T.
      dermatis, T. asahii genotype 3, and T. montevideense, representing serotypes I,
      II, and III, respectively.

PMID- 15583268
TI  - Sequencing needs for viral diagnostics.
AB  - We built a system to guide decisions regarding the amount of genomic sequencing
      required to develop diagnostic DNA signatures, which are short sequences that are
      sufficient to uniquely identify a viral species. We used our existing DNA
      diagnostic signature prediction pipeline, which selects regions of a target
      species genome that are conserved among strains of the target (for reliability,
      to prevent false negatives) and unique relative to other species (for
      specificity, to avoid false positives). We performed simulations, based on
      existing sequence data, to assess the number of genome sequences of a target
      species and of close phylogenetic relatives (near neighbors) that are required to
      predict diagnostic signature regions that are conserved among strains of the
      target species and unique relative to other bacterial and viral species. For DNA
      viruses such as variola (smallpox), three target genomes provide sufficient
      guidance for selecting species-wide signatures. Three near-neighbor genomes are
      critical for species specificity. In contrast, most RNA viruses require four
      target genomes and no near-neighbor genomes, since lack of conservation among
      strains is more limiting than uniqueness. Severe acute respiratory syndrome and
      Ebola Zaire are exceptional, as additional target genomes currently do not
      improve predictions, but near-neighbor sequences are urgently needed. Our results
      also indicate that double-stranded DNA viruses are more conserved among strains
      than are RNA viruses, since in most cases there was at least one conserved
      signature candidate for the DNA viruses and zero conserved signature candidates
      for the RNA viruses.

PMID- 15583269
TI  - Isolates of Burkholderia pseudomallei from Northern Australia are distinct by
      multilocus sequence typing, but strain types do not correlate with clinical
      presentation.
AB  - Melioidosis is the disease caused by the saprophytic organism Burkholderia
      pseudomallei. Previous studies have suggested some strain tropism and
      differential virulence. In this study, we defined strains by multilocus sequence
      typing (MLST) of isolates taken from the Top End of Australia's Northern
      Territory and compared the results with those of other strains typed worldwide.
      We specifically sought clinical and geographical correlates of strain types.
      Among 87 Australian isolates, 48 sequence types were defined. None of the
      sequence types in this study has been found elsewhere in the world. Strains were
      distributed widely throughout the region, and the different presentations of
      disease, including neurological and prostatic infection, were associated with
      many different strains. There was excellent congruence between pulsed-field gel
      electrophoresis and MLST, and the two typing methods had a similar level of
      strain discrimination. The work suggests that host and environmental factors may
      be more important in determining disease presentation than infecting strain type.
      It is possible that the distinct but diverse strain types found in this study
      reflect Australia's geographical isolation over many millions of years.

PMID- 15583270
TI  - Impact of proficiency testing on results of the microscopic agglutination test
      for diagnosis of leptospirosis.
AB  - A proficiency testing scheme for the leptospirosis microscopic agglutination test
      was provided to 37 laboratories in 23 countries in 2002 (round 1) and to 60
      laboratories in 34 countries in 2003 (round 2). Thirty-four laboratories
      participated in both rounds. Each panel consisted of five rabbit serum samples,
      four of which were antisera raised against pathogenic serovars of Leptospira. One
      of these samples was a mixture of two different antisera. The rates of false
      negative results, calculated on the basis of the assumption that serovars within
      a serogroup will cross-react, were 11% for round 1 and 14% for round 2. There
      were regional differences in the rates of false-negative results. The titers
      reported by laboratories testing for the same sample with the same serovar varied
      widely. Laboratories that had previously participated in round 1 reported fewer
      false-negative results in round 2 than new participants (10 and 21%, respectively
      [P = 0.002]) and reported 0.56 false-negative results per participant, whereas
      new participants reported 1.23 false-negative results per participant (P =
      0.041). Laboratories that had previously participated also reported fewer false
      negative results in round 2 than in round 1 when samples common to both rounds
      were tested (5 and 15%, respectively [P = 0.028]). The titers reported by the new
      participants were, on average, lower than those reported by the laboratories that
      had participated previously (P = 0.019) and were significantly more variable (P =
      0.001). Analysis of these results suggests a positive impact of proficiency
      testing on the testing performance of the participating laboratories.

PMID- 15583271
TI  - Evaluation of a bedside immunochromatographic test for detection of adenovirus in
      respiratory samples, by comparison to virus isolation, PCR, and real-time PCR.
AB  - An immunochromatography (IC) kit for human adenovirus (HAdV) was evaluated with
      138 patient nasopharyngeal samples. The samples were collected at a sentinel
      clinic in Japan from January through June 2003. Patients were diagnosed by
      clinical manifestation of pharyngoconjunctival fever (n = 38) or exudative
      tonsillitis (n = 100). The IC kit was positive for 84% (116 of 138) of patients
      diagnosed at bedside. The remaining extract solution of the IC kit test was
      transferred into maintenance medium and tested via laboratory diagnoses. The IC
      kit had 95% sensitivity (116 of 122 patients) with HAdV isolation (isolation) as
      the standard and 91% sensitivity (116 of 128 patients) with PCR as the standard.
      All of the IC kit-positive samples were isolation and PCR positive. Similarly,
      all the isolation-positive samples were PCR positive. Twenty-two IC kit-negative
      samples were evaluated by real-time PCR. Six samples were IC kit negative and
      isolation positive and contained 3.8 x 10(7) to 2.5 x 10(9) copies of the HAdV
      genome/ml. Five samples that were only PCR positive contained 3.0 x 10(4) to 3.8
      x 10(5) copies of the HAdV genome/ml, but one sample was real-time PCR negative.
      We conclude that the IC kit is a useful bedside diagnostic tool for HAdV
      infections because it has 95% sensitivity (compared to isolation), but a negative
      result does not always rule out HAdV infection.

PMID- 15583272
TI  - Amoebal coculture of "Mycobacterium massiliense" sp. nov. from the sputum of a
      patient with hemoptoic pneumonia.
AB  - A nonphotochromogenic, rapidly growing Mycobacterium strain was isolated in pure
      culture from the sputum and the bronchoalveolar fluid of a patient with hemoptoic
      pneumonia by using axenic media and an amoebal coculture system. Both isolates
      grew in less than 7 days at 24 to 37 degrees C with an optimal growth temperature
      of 30 degrees C. The isolates exhibited biochemical and antimicrobial
      susceptibility profiles overlapping those of Mycobacterium abscessus,
      Mycobacterium chelonae, and Mycobacterium immunogenum, indicating that they
      belonged to M. chelonae-M. abscessus group. They differed from M. abscessus in
      beta-galactosidase, beta-N-acetyl-beta-glucosaminidase, and beta-glucuronidase
      activities and by the lack of nitrate reductase and indole production activities,
      as well as in their in vitro susceptibilities to minocycline and doxycycline.
      These isolates and M. abscessus differed from M. chelonae and M. immunogenum by
      exhibiting gelatinase and tryptophane desaminase activities. Their 16S rRNA genes
      had complete sequence identity with that of M. abscessus and >99.6% similarity
      with those of M. chelonae and M. immunogenum. Further molecular investigations
      showed that partial hsp65 and sodA gene sequences differed from that of M.
      abscessus by five and three positions over 441 bp, respectively. Partial rpoB and
      recA gene sequence analyses showed 96 and 98% similarities with M. abscessus,
      respectively. Similarly, 16S-23S rRNA internal transcribed spacer sequence of the
      isolates differed from that of M. abscessus by a A-->G substitution at position
      60 and a C insertion at position 102. Phenotypic and genotypic features of these
      two isolates indicated that they were representative of a new mycobacterial
      species within the M. chelonae-M. abscessus group. Phylogenetic analysis
      suggested that these isolates were perhaps recently derived from M. abscessus. We
      propose the name of "Mycobacterium massiliense" for this new species. The type
      strain has been deposited in the Collection Institut Pasteur as CIP 108297(T) and
      in Culture Collection of the University of Goteborg, Goteborg, Sweden, as CCUG
      48898(T).

PMID- 15583273
TI  - Exploration of biases that affect the interpretation of restriction fragment
      patterns produced by pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) has been used extensively in
      epidemiological investigations of bacteria, especially during food-borne
      outbreaks or nosocomial infections. The relationship between similarities in PFGE
      patterns and true genetic relatedness is poorly understood. In this study,
      computer-simulated populations of Escherichia coli isolates were created by
      mutating the sequence of E. coli K-12 strain MG1655. The simulated populations of
      isolates were then digested, again through simulation, with different restriction
      enzymes and were analyzed for their relatedness by different techniques. Errors
      associated with band determination and band matching were incorporated into the
      analyses, as both of these error types have been shown to affect PFGE
      interpretations. These errors increased the apparent similarities of the
      isolates. The use of multiple enzymes improved the fidelity between the results
      of PFGE analyses and the true sequence similarities. These findings, when they
      are combined with results from laboratory studies, emphasize the need for the
      inclusion of multiple enzymes and additional epidemiological data in order to
      make more accurate interpretations.

PMID- 15583274
TI  - Rapid detection of rifampin resistance in Mycobacterium tuberculosis isolates
      from India and Mexico by a molecular beacon assay.
AB  - We assessed the performance of a rapid, single-well, real-time PCR assay for the
      detection of rifampin-resistant Mycobacterium tuberculosis by using clinical
      isolates from north India and Mexico, regions with a high incidence of
      tuberculosis. The assay uses five differently colored molecular beacons to
      determine if a short region of the M. tuberculosis rpoB gene contains mutations
      that predict rifampin resistance in most isolates. Until now, the assay had not
      been sufficiently tested on samples from countries with a high incidence of
      tuberculosis. In the present study, the assay detected mutations in 16 out of 16
      rifampin-resistant isolates from north India (100%) and in 55 of 64 rifampin
      resistant isolates from Mexico (86%) compared to results with standard
      susceptibility testing. The assay did not detect mutations (a finding predictive
      of rifampin susceptibility) in 37 out of 37 rifampin-susceptible isolates from
      India (100%) and 125 out of 126 rifampin-susceptible isolates from Mexico (99%).
      DNA sequencing revealed that none of the nine rifampin-resistant isolates from
      Mexico, which were misidentified as rifampin susceptible by the molecular beacon
      assay, contained a mutation in the region targeted by the molecular beacons. The
      one rifampin-susceptible isolate from Mexico that appeared to be rifampin
      resistant by the molecular beacon assay contained an S531W mutation, which is
      usually associated with rifampin resistance. Of the rifampin-resistant isolates
      that were correctly identified in the molecular beacon assay, one contained a
      novel L530A mutation and another contained a novel deletion between codons 511
      and 514. Overall, the molecular beacon assay appears to have sufficient
      sensitivity (89%) and specificity (99%) for use in countries with a high
      prevalence of tuberculosis.

PMID- 15583275
TI  - Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis
      of invasive aspergillosis with bronchoalveolar lavage fluid.
AB  - Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in
      hematopoietic stem cell transplant patients. Diagnosis requires microbiological
      or histopathologic demonstration of the organism in tissues; however, cultivation
      of Aspergillus species from respiratory secretions has low diagnostic
      sensitivity. Assays to detect Aspergillus antigen or DNA in bronchoalveolar
      lavage (BAL) fluid could facilitate earlier diagnosis, thereby guiding optimal
      therapy and obviating the need for additional costly and potentially morbid
      diagnostic evaluation. We evaluated the performance of a galactomannan enzyme
      immunoassay (GM EIA; Bio-Rad) by using a range of index cutoffs to define
      positivity and a quantitative PCR (qPCR) assay for the detection of Aspergillus
      species from BAL samples of patients with proven and probable IPA (case patients;
      n = 49) and without IPA (control patients; n = 50). The sensitivity of the GM EIA
      was 61% with an index cutoff of 1.0 and 76% with an index cutoff of 0.5; the
      corresponding specificities were 98 and 94%, respectively. The sensitivity and
      specificity of qPCR assay were 67 and 100%, respectively. The sensitivity with 22
      culture-negative BAL specimens from patients with IPA was 41% for GM EIA with an
      index cutoff of 1.0, 59% for GM EIA with an index cutoff of 0.5, and 36% for qPCR
      assay. GM EIA indices and DNA quantities corresponded to BAL fungal burdens, with
      culture-positive samples having larger amounts of antigen and DNA compared to
      culture-negative samples. GM EIA and qPCR assay add to the sensitivity of BAL for
      diagnosing IPA in high-risk patients, with excellent specificity. Adjunctive use
      of these tests may reduce dependence on invasive diagnostic procedures.

PMID- 15583276
TI  - Culture-independent identification of periodontitis-associated Porphyromonas and
      Tannerella populations by targeted molecular analysis.
AB  - Periodontitis is the commonest bacterial disease of humans and is the major cause
      of adult tooth loss. About half of the oral microflora is unculturable; and 16S
      rRNA PCR, cloning, and sequencing techniques have demonstrated the high level of
      species richness of the oral microflora. In the present study, a PCR primer set
      specific for the genera Porphyromonas and Tannerella was designed and used to
      analyze the bacterial populations in subgingival plaque samples from inflamed
      shallow and deep sites in subjects with periodontitis and shallow sites in age-
      and sex-matched controls. A total of 308 clones were sequenced and found to
      belong to one of six Porphyromonas or Tannerella species or phylotypes, one of
      which, Porphyromonas P3, was novel. Tannerella forsythensis was found in
      significantly higher proportions in patients than in controls. Porphyromonas
      catoniae and Tannerella phylotype BU063 appeared to be associated with shallow
      sites. Targeted culture-independent molecular ecology studies have a valuable
      role to play in the identification of bacterial targets for further
      investigations of the pathogenesis of bacterial infections.

PMID- 15583277
TI  - Genotypic and phenotypic heterogeneity among Mycobacterium tuberculosis isolates
      from pulmonary tuberculosis patients.
AB  - Although the heterogeneity of Mycobacterium tuberculosis populations and the
      existence of mixed infections are now generally accepted, systematic studies on
      their relative importance are rare. In the present study, 10 individual colonies
      of each M. tuberculosis isolate (primary isolate) from 97 tuberculosis patients
      in a primarily human immunodeficiency virus-negative population were screened for
      heterogeneity and detectable mixed infections by spoligotyping, IS6110-based
      restriction fragment length polymorphism analysis, and mycobacterial interspersed
      repetitive unit-variable number of tandem repeat typing. The MICs of
      antituberculosis drugs for colonies with divergent fingerprints were determined.
      Infections with different bacterial subpopulations were detected in the samples
      from eight patients (8.2%), and the frequency of detectable mixed infections in
      the study population was estimated to be 2.1%. Genotypic variations were found to
      be independent of the drug susceptibilities, and the various molecular markers
      evolved independently in most cases. The predominant strains and the primary
      isolates always had concordant drug susceptibility and MIC testing results. These
      findings have implications on the interpretation of molecular epidemiology
      results for patient follow-up and in transmission studies.

PMID- 15583278
TI  - Burkholderia cepacia is associated with pulmonary hypertension and increased
      mortality among cystic fibrosis patients.
AB  - The aim of the study was to evaluate the impact of Burkholderia cepacia on
      cardiovascular status and mortality in cystic fibrosis. Seven patients infected
      with B. cepacia were matched with 31 patients not infected with this organism for
      gender, age, height, weight, genotype, and percent predicted forced expiratory
      volume in one second, partial arterial oxygen pressure, and pancreatic
      sufficiency status. The pulmonary artery systolic pressure, as assessed by
      transthoracic echocardiography, was significantly higher in patients infected
      with B. cepacia (61.3 +/- 17.2 mm Hg) than in controls (37.3 +/- 13.9 mm Hg; P =
      0.02), and the mean acceleration time was significantly lower (77 +/- 33 ms
      versus 108 +/- 25 ms; P = 0.02). The 6-month mortality was significantly higher
      in patients infected with B. cepacia (57% versus 16%; P = 0.02). Six of the seven
      patients infected with B. cepacia harbored the same ribotype (genomovar II, B.
      multivorans). Pulmonary hypertension was significantly more frequent in patients
      infected by B. cepacia and could contribute to the increased mortality rate.

PMID- 15583279
TI  - Nicoletella semolina gen. nov., sp. nov., a new member of Pasteurellaceae
      isolated from horses with airway disease.
AB  - Gram-negative, nonmotile bacteria that are catalase, oxidase, and urease positive
      are regularly isolated from the airways of horses with clinical signs of
      respiratory disease. On the basis of the findings by a polyphasic approach, we
      propose that these strains be classified as Nicoletella semolina gen. nov, sp.
      nov., a new member of the family Pasteurellaceae. N. semolina reduces nitrate to
      nitrite but is otherwise biochemically inert; this includes the lack of an
      ability to ferment glucose and other sugars. Growth is fastidious, and the
      isolates have a distinctive colony morphology, with the colonies being dry and
      waxy and looking like a semolina particle that can be moved around on an agar
      plate without losing their shape. DNA-DNA hybridization data and multilocus
      phylogenetic analysis, including 16S rRNA gene (rDNA), rpoB, and infB sequencing,
      clearly placed N. semolina as a new genus in the family Pasteurellaceae. In all
      the phylogenetic trees constructed, N. semolina is on a distinct branch
      displaying approximately 5% 16S rDNA, approximately 16% rpoB, and approximately
      20% infB sequence divergence from its nearest relative within the family
      Pasteurellaceae. High degrees of conservation of the 16S rDNA (99.8%), rpoB
      (99.6%), and infB (99.7%) sequences exist within the species, indicating that N.
      semolina isolates not only are phenotypically homogeneous but also are
      genetically homogeneous. The type strain of N. semolina is CCUG43639(T)
      (DSM16380(T)).

PMID- 15583280
TI  - Differentiation of Campylobacter coli, Campylobacter jejuni, Campylobacter lari,
      and Campylobacter upsaliensis by a multiplex PCR developed from the nucleotide
      sequence of the lipid A gene lpxA.
AB  - We describe a multiplex PCR assay to identify and discriminate between isolates
      of Campylobacter coli, Campylobacter jejuni, Campylobacter lari, and
      Campylobacter upsaliensis. The C. jejuni isolate F38011 lpxA gene, encoding a UDP
      N-acetylglucosamine acyltransferase, was identified by sequence analysis of an
      expression plasmid that restored wild-type lipopolysaccharide levels in
      Escherichia coli strain SM105 [lpxA(Ts)]. With oligonucleotide primers developed
      to the C. jejuni lpxA gene, nearly full-length lpxA amplicons were amplified from
      an additional 11 isolates of C. jejuni, 20 isolates of C. coli, 16 isolates of C.
      lari, and five isolates of C. upsaliensis. The nucleotide sequence of each
      amplicon was determined, and sequence alignment revealed a high level of species
      discrimination. Oligonucleotide primers were constructed to exploit species
      differences, and a multiplex PCR assay was developed to positively identify
      isolates of C. coli, C. jejuni, C. lari, and C. upsaliensis. We characterized an
      additional set of 41 thermotolerant isolates by partial nucleotide sequence
      analysis to further demonstrate the uniqueness of each species-specific region.
      The multiplex PCR assay was validated with 105 genetically defined isolates of C.
      coli, C. jejuni, C. lari, and C. upsaliensis, 34 strains representing 12
      additional Campylobacter species, and 24 strains representing 19 non
      Campylobacter species. Application of the multiplex PCR method to whole-cell
      lysates obtained from 108 clinical and environmental thermotolerant Campylobacter
      isolates resulted in 100% correlation with biochemical typing methods.

PMID- 15583281
TI  - Shedding of ovine herpesvirus 2 in sheep nasal secretions: the predominant mode
      for transmission.
AB  - Ovine herpesvirus 2 (OvHV-2), the major causative agent of malignant catarrhal
      fever in ruminant species worldwide, has never been propagated in vitro. Using
      real-time PCR, a striking, short-lived, peak of viral DNA, ranging from 10(5) to
      over 10(8) copies/2 microg of DNA, was detected in nasal secretions from over
      60.7% of adolescent sheep (n = 56) at some point during the period from 6 to 9
      months of age. In contrast, only about 18% of adult sheep (n = 33) experienced a
      shedding episode during the study period. The general pattern of the appearance
      of viral DNA in nasal secretions was a dramatic rise and subsequent fall within
      24 to 36 h, implying a single cycle of viral replication. These episodes occurred
      sporadically and infrequently, but over the 3-month period most of the 56 lambs
      (33, or 60.7%) experienced at least one episode. No corresponding fluctuations in
      DNA levels were found in either peripheral blood leukocytes or plasma. In a DNase
      protection assay, complete, enveloped OvHV-2 virions were demonstrated in the
      nasal secretions of all sheep examined during the time when they were
      experiencing an intense shedding episode. OvHV-2 infectivity in nasal secretions
      was also demonstrated by aerosolization of the secretions into OvHV-2-negative
      sheep. The data herein show that nasal shedding is the major mode of OvHV-2
      transmission among domestic sheep and that adolescents represent the highest risk
      group for transmission.

PMID- 15583282
TI  - "Bacteroides nordii" sp. nov. and "Bacteroides salyersae" sp. nov. isolated from
      clinical specimens of human intestinal origin.
AB  - Two groups of unknown bacteria, which phenotypically resemble members of the
      Bacteroides fragilis group but phylogenetically display >5% 16S rRNA gene
      sequence divergence from their nearest validly described species, Bacteroides
      thetaiotaomicron, were characterized by phenotypic and molecular taxonomic
      methods. Phylogenetically and phenotypically, the unidentified bacteria displayed
      a relatively close association with each other. However, a 16S rRNA gene sequence
      divergence of approximately 4% between the two unknown bacteria, as well as
      distinguishable biochemical characteristics, demonstrates that these organisms
      are genotypically and phenotypically distinct, and each group may represent a
      previously unknown subline within the Bacteroides phylogenetic cluster.
      Subsequent DNA-DNA hybridization studies confirmed that the two novel organisms
      were indeed distinct from each other. The previously described species closest to
      both of them is B. thetaiotaomicron (approximately 94% sequence similarity), but
      they can be differentiated easily from B. thetaiotaomicron by virtue of not
      utilizing trehalose. DNA-DNA pairing studies also documented the separateness of
      the unknown species and B. thetaiotaomicron. Based on the phenotypic and
      phylogenetic findings, two new species, "Bacteroides nordii" sp. nov. and
      "Bacteroides salyersae" sp. nov, are proposed. The G+C content of the DNA is 41.4
      mol% for Bacteroides nordii and 42.0 mol% for Bacteroides salyersae. The type
      strains of Bacteroides nordii and Bacteroides salyersae are WAL 11050 (ATCC BAA
      998 or CCUG 48943) and WAL 10018 (ATCC BAA-997 or CCUG 48945), respectively.

PMID- 15583283
TI  - Trends in antimicrobial resistance in 1,968 invasive Streptococcus pneumoniae
      strains isolated in Spanish hospitals (2001 to 2003): decreasing penicillin
      resistance in children's isolates.
AB  - To address the public health problem of antibiotic resistance, the European Union
      (EU) founded the European Antimicrobial Resistance Surveillance System. A network
      of 40 hospitals that serve approximately 30% of the Spanish population (about 12
      million) participated. Each laboratory reported data on antimicrobial
      susceptibility testing using standard laboratory procedures that were evaluated
      by an external quality control program. The antibiotic consumption data were
      obtained from the National Health System. We compared the antibiotic
      susceptibility of Spanish isolates of invasive Streptococcus pneumoniae (2001 to
      2003) with antibiotic consumption. Invasive S. pneumoniae was isolated from 1,968
      patients, 20% of whom were children at or below the age of 14 years. Of non
      penicillin-susceptible strains (35.6%; 95% confidence interval, 34 to 37.2),
      26.4% were considered intermediate and 9.2% were considered resistant. Between
      2001 and 2003, penicillin resistance decreased from 39.5 to 33% overall and from
      60.4 to 41.2% in children at or below the age of 14 years (P = 0.002). Resistance
      to erythromycin was at 26.6%, and coresistance with penicillin was at 19.1%. Of
      total isolates, the ciprofloxacin MIC was >2 mug/ml for 2.1%, with numbers
      increasing from 0.4% (2001) to 3.9% (2003). Total antibiotic use decreased from
      21.66 to 19.71 defined daily doses/1,000 inhabitants/day between 1998 and 2002.
      While consumption of broad-spectrum penicillins, cephalosporins, and erythromycin
      declined, use of amoxicillin-clavulanate and quinolones increased by 17.5 and
      27%, respectively. The frequency of antibiotic resistance in invasive S.
      pneumoniae in Spain was among the highest in the EU. However, a significant
      decrease in penicillin resistance was observed in children. This decrease
      coincided with the introduction of a heptavalent conjugate pneumoccocal vaccine
      (June 2001) and with a global reduction in antibiotic consumption levels.

PMID- 15583284
TI  - Detection of methicillin-resistant Staphylococcus aureus directly from nasal swab
      specimens by a real-time PCR assay.
AB  - Screening for colonization with methicillin-resistant Staphylococcus aureus
      (MRSA) is a key aspect of infection control to limit the nosocomial spread of
      this organism. Current methods for the detection of MRSA in clinical microbiology
      laboratories, including molecularly based techniques, require a culture step and
      the isolation of pure colonies that result in a minimum of 20 to 24 h until a
      result is known. We describe a qualitative in vitro diagnostic test for the rapid
      detection of MRSA directly from nasal swab specimens (IDI-MRSA; Infectio
      Diagnostic, Inc., Sainte-Foy, Quebec, Canada), based upon a real-time PCR and
      direct detection of MRSA via amplicon hybridization with a fluorogenic target
      specific molecular beacon probe. Samples from 288 patients were analyzed for the
      presence of MRSA with the IDI-MRSA assay, compared to detection by either direct
      plating or enrichment broth selective culture methods. The diagnostic values for
      this MRSA screening method were 91.7% sensitivity, 93.5% specificity, 82.5%
      positive predictive value, and 97.1% negative predictive value when compared to
      culture-based methods. The time from the start of processing of specimen to
      result was approximately 1.5 h. In our hands, the IDI-MRSA assay is a sensitive
      and specific test for detection of nasal colonization with MRSA and providing for
      same-day results, allowing more efficient and effective use of infection control
      resources to control MRSA in health care facilities.

PMID- 15583285
TI  - Pulsed-field gel electrophoresis study of Mycobacterium abscessus isolates
      previously affected by DNA degradation.
AB  - DNA degradation (which results in a smear pattern) occurs with almost 50% of
      Mycobacterium abscessus strains during pulsed-field gel electrophoresis (PFGE).
      We assessed the potential benefit of using thiourea-containing buffer with M.
      abscessus by studying 69 isolates not previously typeable by PFGE (i.e., those
      with a smear pattern). Random (epidemiologically unrelated) isolates that were
      typeable (no smear pattern) were included as controls. Genomic DNA was digested
      with DraI, XbaI, and AseI. PFGE gels were run in regular gel buffer with and
      without 100 muM thiourea. All 69 isolates that generated smear patterns had clear
      band profiles when the thiourea buffer was used. These isolates were divided into
      only 30 patterns with DraI, 20 patterns with XbaI, and 20 patterns with AseI. The
      molecular profiles were all closely or possibly related, and the differences
      between the isolates ranged from zero to six bands. By multilocus enzyme
      electrophoresis (MEE), 45 of 53 smear isolates (85%) belonged to two closely
      related electrophoretic types. These isolates contained at least one enzyme
      allele seen almost exclusively in this group. Isolates without smear patterns
      were unaffected by thiourea and produced unrelated PFGE profiles, as well as
      multiple MEE types. The hsp65 and 16S rRNA gene sequences of the isolates with
      smear patterns were identical to those of M. abscessus type strain ATCC 19977,
      which had a nonsmear pattern, suggesting that this clone is a subgroup within M.
      abscessus. This demonstrates that the inability to type M. abscessus by PFGE is
      associated with a single clone of organisms.

PMID- 15583286
TI  - Phenotypic profiles of enterotoxigenic Escherichia coli associated with early
      childhood diarrhea in rural Egypt.
AB  - Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity
      and mortality in young children in countries with limited resources. We
      determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from
      Egyptian children under 3 years of age who participated in a 3-year population
      based study. For each strain, we ascertained enterotoxin and colonization factor
      (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one
      percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed
      heat-labile enterotoxin (LT) alone, and 12% expressed both toxins. The most
      common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli
      surface antigen 6 (CS6) (9%), CS14 (6%), and CS1 plus CS3 (4%). Fifty-nine
      percent of the strains did not express any of the 12 CFs included in our test
      panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim
      sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to
      quinolone antibiotics was rarely detected. As for the distribution of observed
      serotypes, there was an unusually wide diversity of O antigens and H types
      represented among the 915 ETEC strains. The most commonly recognized composite
      ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST
      CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal
      episodes associated with ETEC strains bearing common composite phenotypes were
      consistent with discrete community outbreaks either within a single or over
      successive warm seasons. These data suggest that a proportion of the disease that
      is endemic to young children in rural Egypt represents the confluence of small
      epidemics by clonally related ETEC strains that are transiently introduced or
      that persist in a community reservoir.

PMID- 15583287
TI  - Practical implementation of a multiplex PCR for acute respiratory tract
      infections in children.
AB  - Molecular testing for acute respiratory infections (ARIs) has documented value
      but limited implementation due to questions that typically slow the acceptance of
      new tests. This study sought to address these questions and achieve
      implementation. Rhinovirus was added to a nested multiplex PCR (M-PCR),
      increasing its diagnostic yield. Over one winter, three hospital pediatric
      departments used the M-PCR to complement their direct fluorescent-antibody assay
      (DFA) for respiratory syncytial virus (RSV). Clinicians recorded "pretest
      probability estimates" (using continuous scales for various pathogen groups) for
      comparison with test results; treatments and test turnaround times were also
      recorded. Transnasal and throat swabs, with or without nasopharyngeal aspirate
      (NPA), were M-PCR tested. NPA-containing sample sets found to be RSV positive by
      DFA were not further tested. Single PCR for human metapneumovirus (hMPV) was
      performed retrospectively. Of 178 ARI episodes representing 172 patients, NPA was
      included in 97 sample sets; 54 (56%) were determined to be RSV positive. The
      other NPA-containing sample sets (n = 43) yielded 27 findings (63%), and the swab
      only sets (n = 81) yielded 47 findings (58%); rhinovirus was found most often.
      Testing for hMPV yielded seven positive results. M-PCR median turnaround times
      were 4 days in swab-only samples and 5 days with NPA. Antibiotics were prescribed
      in 50 episodes, at rates similar for RSV and rhinovirus. Pretest probability
      estimates of a viral cause were lower in episodes caused by rhinovirus than in
      episodes caused by RSV. The hospitals continued to use M-PCR for NPA-containing
      samples found to be RSV negative by DFA. Test implementation is more likely with
      higher diagnostic yield and a protocol that reflects day-to-day clinical and
      laboratory operations.

PMID- 15583288
TI  - Genetic profile of an Oka varicella vaccine virus variant isolated from an infant
      with zoster.
AB  - Varicella virus vaccine strain Oka (V-Oka) has in rare cases caused zoster in
      vaccinated people. Despite broad usage of V-Oka, little is known about varicella
      zoster virus genomic sequence variation of strains in vaccine and isolates from
      patients with vaccine adverse events. Direct sequencing of 20 regions of V-Oka
      GSK was compared to the sequences of the original V-Oka-Biken, GlaxoSmithKline
      Oka vaccine (V-Oka-GSK), and Oka-parental (P-Oka) strains. We analyzed single
      nucleotide polymorphisms (SNP) differentiating the Oka parental and Oka vaccine
      strains identified in open reading frames (ORFs) 6, 9A, 10, 21, 31, 39, 50, 51,
      52, 54, 55, and 59 and eight base substitutions within ORF 62. Sixteen of these
      SNP impose an amino acid change in the corresponding gene product. The genotypic
      analysis revealed that (i) both V-Oka-GSK and V-Oka-Biken comprise mixtures of
      strains represented in variable proportion from lot to lot; (ii) V-Oka-GSK/zoster
      isolated from the zoster patient had six wild-type SNP in ORF 9A, 10, 21, 52, 55,
      and 62 (mutation 108838); (iii) none of the six revertant SNP would reliably
      discriminate Oka vaccine from the wild type; and (iv) the genomic variation found
      in V-Oka/zoster might be associated with changes in the biological behavior of
      the virus. Further studies will be needed to identify potential virulence factors
      in variant vaccine strains.

PMID- 15583289
TI  - Direct identification of gram-positive cocci from routine blood cultures by using
      AccuProbe tests.
AB  - Rapid and reliable identification of bacteria directly from blood cultures is
      important in clinical practice to guide appropriate antibiotic therapy. In this
      study, the performance of the AccuProbe (Gen-Probe, Inc., San Diego, Calif.) in
      direct identification of Staphylococcus aureus, Streptococcus pneumoniae,
      enterococci, and group A and B streptococci from positive blood culture bottles
      was evaluated by using 6-year routine clinical laboratory blood culture material
      from Paijat-Hame Central Hospital, Lahti, Finland. With the enterococcal and
      group A and B streptococcal probes, the diagnostic performance of the test was
      excellent at a cutoff value of 50,000 relative light units (RLU) as recommended
      by the manufacturer. However, with the S. aureus probe, although the specificity
      was very high (99.8%), the sensitivity was low (72.4%). To improve the clinical
      usability of the direct AccuProbe identification, optimal cutoff values for the
      individual AccuProbe tests were defined by using receiver-operating
      characteristic analysis. Consequently, cutoff values for S. aureus and S.
      pneumoniae tests were adjusted to 30,000 RLU and for enterococci and to 55,000
      RLU for group A and B streptococci. With these adjustments, the performance of
      the AccuProbe tests, especially that for S. aureus, was significantly improved.

PMID- 15583290
TI  - Detection of virulence-associated genes not useful for discriminating between
      invasive and commensal Staphylococcus epidermidis strains from a bone marrow
      transplant unit.
AB  - Because of their biofilm-forming capacity, invasive Staphylococcus epidermidis
      isolates, which cause the majority of nosocomial catheter-related bloodstream
      infections (BSIs), are thought to be selected at the time of catheter insertion
      from a population of less virulent commensal strains. This fact allows the
      prediction that invasive and contaminating strains can be differentiated via
      detection of virulence-associated genes. However, the hospital environment may
      pave the way for catheter-related infections by promoting a shift in the
      commensal bacterial population toward strains with enhanced virulence. The
      distribution of virulence-associated genes (icaADBC, aap, atlE, bhp, fbe, embp,
      mecA, IS256, and IS257), polysaccharide intercellular adhesin synthesis, and
      biofilm formation were investigated in S. epidermidis strains from independent
      episodes of catheter-related BSIs in individuals who have received bone marrow
      transplantation (BMT). The results were compared with those obtained for
      commensal S. epidermidis isolates from hospitalized patients after BMT and from
      healthy individuals, respectively. The clonal relationships of the strains were
      investigated by pulsed-field gel electrophoresis. icaADBC, mecA, and IS256 were
      significantly more prevalent in BSI isolates than in commensal isolates from
      healthy individuals. However, the prevalence of any of the genes in clonally
      independent, endogenous commensal strains from BMT patients did not differ from
      that in invasive BSI strains. icaADBC and methicillin resistance, factors
      important for the establishment of catheter-related infections, already ensure
      survival of the organisms in their physiological habitat in the hospital
      environment, resulting in a higher probability of contamination of indwelling
      medical devices with virulent S. epidermidis strains. The dynamics of S.
      epidermidis populations reveal that detection of icaADBC and mecA is not suitable
      for discriminating invasive from contaminating S. epidermidis strains.

PMID- 15583291
TI  - Prevalence and mechanisms of erythromycin resistance in group A and group B
      Streptococcus: implications for reporting susceptibility results.
AB  - Increased rates of erythromycin resistance among group B Streptococcus (GBS) and
      group A Streptococcus (GAS) have been reported. Cross-resistance to clindamycin
      may be present, depending on the mechanism of resistance. We determined the
      prevalence of macrolide-resistant determinants in GBS and GAS isolates to guide
      the laboratory reporting of erythromycin and clindamycin susceptibility.
      Susceptibilities were determined by the disk diffusion and broth microdilution
      methods. Inducible and constitutive resistance to clindamycin was determined by
      the double-disk diffusion method. The presence of the ermTR, ermB, and mefA genes
      was confirmed by PCR. Of the 338 GBS isolates, 55 (17%) were resistant to
      erythromycin, whereas 26 (8%) were resistant to clindamycin. The erm methylase
      gene was identified in 48 isolates, 22 of which had inducible resistance to
      clindamycin and 26 of which had constitutive resistance to clindamycin. The
      remaining seven resistant isolates had mefA. Of the 593 GAS isolates, 49 (8%) and
      6 (1%) isolates were resistant to erythromycin and clindamycin, respectively.
      Erythromycin resistance was due to mefA in 33 isolates, whereas 14 isolates had
      erm-mediated resistance (9 isolates had inducible resistance and 5 isolates had
      constitutive resistance). In our population, erythromycin resistance in GAS was
      predominantly mediated by mefA and erythromycin resistance in GBS was
      predominantly mediated by erm. Regional differences in mechanisms of resistance
      need to be taken into consideration when deciding whether to report clindamycin
      susceptibility results on the basis of in vitro test results. Testing by the
      double-disk diffusion method would be an approach that could be used to address
      this issue, especially for GAS.

PMID- 15583292
TI  - Phylogeny and evolution of medical species of Candida and related taxa: a
      multigenic analysis.
AB  - Hemiascomycetes are species of yeasts within the order Saccharomycetales. The
      order encompasses disparate genera with a variety of life styles, including
      opportunistic human pathogens (e.g., Candida albicans), plant pathogens (e.g.,
      Eremothecium gossypii), and cosmopolitan yeasts associated with water and
      decaying vegetation. To analyze the phylogeny of medically important species of
      yeasts, we selected 38 human pathogenic and related strains in the order
      Saccharomycetales. The DNA sequences of six nuclear genes were analyzed by
      maximum likelihood and Bayesian phylogenetic methods. The maximum likelihood
      analysis of the combined data for all six genes resolved three major lineages
      with significant support according to Bayesian posterior probability. One clade
      was mostly comprised of pathogenic species of Candida. Another major group
      contained members of the family Metschnikowiaceae as a monophyletic group, three
      species of Debaryomyces, and strains of Candida guilliermondii. The third clade
      consisted exclusively of species of the family Saccharomycetaceae. Analysis of
      the evolution of key characters indicated that both codon reassignment and
      coenzyme Q(9) likely had single origins with multiple losses. Tests of correlated
      character evolution revealed that these two traits evolved independently.

PMID- 15583293
TI  - Detection of four Plasmodium species in blood from humans by 18S rRNA gene
      subunit-based and species-specific real-time PCR assays.
AB  - There have been reports of increasing numbers of cases of malaria among migrants
      and travelers. Although microscopic examination of blood smears remains the "gold
      standard" in diagnosis, this method suffers from insufficient sensitivity and
      requires considerable expertise. To improve diagnosis, a multiplex real-time PCR
      was developed. One set of generic primers targeting a highly conserved region of
      the 18S rRNA gene of the genus Plasmodium was designed; the primer set was
      polymorphic enough internally to design four species-specific probes for P.
      falciparum, P. vivax, P. malarie, and P. ovale. Real-time PCR with species
      specific probes detected one plasmid copy of P. falciparum, P. vivax, P.
      malariae, and P. ovale specifically. The same sensitivity was achieved for all
      species with real-time PCR with the 18S screening probe. Ninety-seven blood
      samples were investigated. For 66 of them (60 patients), microscopy and real-time
      PCR results were compared and had a crude agreement of 86% for the detection of
      plasmodia. Discordant results were reevaluated with clinical, molecular, and
      sequencing data to resolve them. All nine discordances between 18S screening PCR
      and microscopy were resolved in favor of the molecular method, as were eight of
      nine discordances at the species level for the species-specific PCR among the 31
      samples positive by both methods. The other 31 blood samples were tested to
      monitor the antimalaria treatment in seven patients. The number of parasites
      measured by real-time PCR fell rapidly for six out of seven patients in parallel
      to parasitemia determined microscopically. This suggests a role of quantitative
      PCR for the monitoring of patients receiving antimalaria therapy.

PMID- 15583294
TI  - Development of a multilocus sequence typing scheme for the opportunistic pathogen
      Pseudomonas aeruginosa.
AB  - A multilocus sequence typing (MLST) scheme has been developed for Pseudomonas
      aeruginosa which provides molecular typing data that are highly discriminatory
      and electronically portable between laboratories. MLST data confirm the data from
      previous studies that suggest that P. aeruginosa is best described as nonclonal
      but as having an epidemic population. The index of association was 0.17,
      indicating a freely recombining population; however, there was evidence of
      clusters of closely related strains or clonal complexes among the members of this
      population. It is apparent that the sequence types (STs) from single isolates,
      representing each of the present epidemic clones in the United Kingdom from
      Liverpool, Manchester, and the West Midlands, are not closely related to each
      other. This suggests distinct evolutionary origins for each of these epidemic
      clones in the United Kingdom. Furthermore, these clones are distinct from
      European clone C. Comparison of the results of MLST with those of toxA typing and
      serotyping revealed that strains with identical STs may possess different toxA
      types and diverse serotypes. Given that recombination is important in the
      population of P. aeruginosa, the lack of a linkage between toxA type and serotype
      is not surprising and reveals the strength of the MLST approach for obtaining a
      better understanding of the epidemiology of P. aeruginosa.

PMID- 15583295
TI  - Epidemiology and typing of Staphylococcus aureus strains isolated from
      bloodstream infections.
AB  - We carried out an epidemiological study covering 2,365,067 patient days of
      hospitalization between 2000 and 2003. During this time, 413 Staphylococcus
      aureus bloodstream infections occurred. This corresponds to 15% of the 2,676
      bloodstream infections observed during this period in the 31 hospitals in our
      region of France, which has 2.5 million inhabitants. The incidence of nosocomial
      S. aureus bloodstream infections was 0.11 per 1,000 days of hospitalization. The
      prevalence of methicillin-resistant S. aureus (MRSA) strains, of which 13% were
      nonmultiresistant MRSA (NORSA), was 33%, and this percentage was stable over the
      4 years. In contrast, the prevalence of S. aureus strains susceptible to
      methicillin but resistant to quinolones or susceptible to methicillin but
      multiresistant to antibiotics (EMSSA strains) increased from 4% in 2000 to 23% in
      2003. As previously reported, MRSA strains were mostly recovered from nosocomial
      bloodstream infections, whereas NORSA strains-generally considered to be
      responsible for community-acquired infections-were always isolated from
      nosocomial bloodstream infections. Pulsed-field gel electrophoresis (PFGE)
      analysis of 109 MRSA strains and 15 EMSSA strains demonstrated clonal diffusion
      of the three major French MRSA clones and revealed considerable genetic
      heterogeneity among EMSSA strains. Although no epidemiologically related NORSA
      strains clustered in particular PFGE groups, the distribution of MRSA strains
      isolated from bloodstream infections according to the portal of entry (vascular
      devices, pulmonary, and urinary) was not random for the major PFGE clones,
      suggesting that each MRSA lineage displays particular virulence features.

PMID- 15583296
TI  - Novel 180- and 480-base-pair insertions in African and African-American strains
      of Helicobacter pylori.
AB  - Helicobacter pylori is a genetically diverse bacterial species that chronically
      infects human stomachs and sometimes causes severe gastroduodenal disease.
      Studies of polymorphic DNA sequences can suggest geographic origins of individual
      strains. Here, we describe a 180-bp insertion (ins180), which is just after the
      translation stop of a gene of unknown function, near the promoter of jhp0152
      jhp0151 two-component signal transduction genes in strain J99, and absent from
      this site in strain 26695. This ins180 insertion was found in 9 of 9 Gambian
      (West African), 9 of 20 (45%) South African, and 9 of 40 (23%) Spanish strains
      but in only 2 of 20 (10%) North American strains and none of 20 Lithuanian, 20
      Indian, and 20 Japanese strains. Four South African isolates that lacked ins180
      and that belonged to an unusual outlier group contained a 480-bp insertion at
      this site (ins480), whereas none of 181 other strains screened contained ins480.
      In further tests 56% (10 of 18) of strains from African Americans but only 17% (3
      of 18) of strains from Caucasian Americans carried ins180 (P < 0.05). Thus, the
      H. pylori strains of modern African Americans seem to retain traces of African
      roots, despite the multiple generations since their ancestors were taken from
      West Africa. Fragmentary ins180-like sequences were found at numerous sites in H.
      pylori genomes, always between genes. Such sequences might affect regulation of
      transcription and could facilitate genome rearrangement by homologous
      recombination. Apparent differences between African-American and Caucasian
      American H. pylori gene pools may bear on our understanding of H. pylori
      transmission and disease outcome.

PMID- 15583297
TI  - High prevalence of natural Chlamydophila species infection in calves.
AB  - We investigated the acquisition and prevalence of Chlamydophila sp. infection in
      calves. Specimens were collected at weekly intervals from birth to week 12
      postpartum from 40 female Holstein calf-dam pairs in a dairy herd. Real-time PCR
      detected, quantified, and differentiated Chlamydophila 23S rRNA gene DNA from
      vaginal cytobrush swabs and milk samples. Chemiluminescence enzyme-linked
      immunosorbent assay with lysed Chlamydophila abortus or Chlamydophila pecorum
      elementary body antigens quantified antibodies against Chlamydophila spp. in
      sera. Chlamydophila sp. DNA was found in 61% of calves and 20% of dams in at
      least one positive quantitative PCR. In calves, clinically inapparent C. pecorum
      infection with low organism loads was fivefold more prevalent than C. abortus
      infection and was most frequently detected by vaginal swabs compared to rectal or
      nasal swabs. In dams, C. abortus dominated in milk and C. pecorum dominated in
      the vagina. The group size of calves correlated positively (P < 0.01) with
      Chlamydophila infection in quadratic, but not linear, regression. Thus, a
      doubling of the group size was associated with a fourfold increase in frequency
      and intensity of Chlamydophila infection. For groups of 14 or 28 calves,
      respectively, logistic regression predicted a 9 or 52% probability of infection
      of an individual calf and a 52 or 99.99% probability of infection of the group.
      Anti-Chlamydophila immunoglobulin M antibodies in Chlamydophila PCR-positive
      calves and dams and in dams that gave birth to calves that later became positive
      were significantly higher than in PCR-negative animals (P </= 0.02).
      Collectively, crowding strongly enhances the frequency and intensity of highly
      prevalent Chlamydophila infections in cattle.

PMID- 15583298
TI  - Emergence and spread of community-associated methicillin-resistant Staphylococcus
      aureus in rural Wisconsin, 1989 to 1999.
AB  - We investigated the emergence and spread of community-associated strains of
      methicillin-resistant Staphylococcus aureus (CA-MRSA) in central and northern
      Wisconsin by determining the temporal and clonal relationships and geographic
      expansion among 581 of 956 clinical isolates of MRSA collected between 1989 and
      1999. Based on EcoRI plasmid profiles (PP), two types, PP-11 and PP-13, were
      highly stable over time and were consistently associated with multidrug-sensitive
      strains recovered from outpatients treated at Native American community clinics.
      Pulsed-field gel electrophoresis (PFGE) yielded six major clonal groups (MCGs)
      and 19 minor clonal groups. The six MCGs represented 82% of the isolates. All
      strains with either PP-11 or -13 were present in MCG-2. Eighty-nine percent of
      the isolates in MCG-2 originated from Native American clinics, and 90% belonged
      to two PFGE types (19 and 20), the types associated with an outbreak of MRSA in a
      Native American community in 1992. MCG-2 isolates were multidrug sensitive,
      harbored type IVa staphylococcal cassette chromosome mec, and were very closely
      related by PFGE to the Midwestern CA-MRSA strain MW2. MCG-2 strains were mostly
      obtained from skin infections and affected patients with a mean age of 24 (+/
      18.0) years. MCG-2 strains spread to four additional Native American communities
      and 20 other communities. Our findings suggest that CA-MRSA in Wisconsin likely
      originated in Native American communities in the early 1990s and since has become
      widespread throughout the state. Two early CA-MRSA strains (WI-33 and WI-34) in
      Wisconsin represent progenitors of the MW2 strain, based on their almost
      indistinguishable genotypic characteristics.

PMID- 15583299
TI  - Genetic analysis of diverse disease-causing pneumococci indicates high levels of
      diversity within serotypes and capsule switching.
AB  - We have used multilocus sequence typing (MLST) and serotyping to build a
      phylogenetic framework for pneumococcal disease isolates in Scotland that
      provides a snapshot of the relationships between capsular type and genotype. The
      results show that while the MLST type correlates with the serotype, isolates
      within a serotype can belong to a number of individual clonal complexes or
      sequence types (STs). We also show that isolates of the same ST can express
      different capsular polysaccharides, i.e., display capsular switching, and that
      this phenomenon is observed both for capsular types commonly isolated from
      patients with invasive disease and for serogroups less commonly isolated from
      patients with invasive disease but which may commonly be carried asymptomatically
      in the human nasopharynx.

PMID- 15583300
TI  - Clinical and laboratory features of Mycobacterium porcinum.
AB  - Recent molecular studies have shown Mycobacterium porcinum, recovered from cases
      of lymphadenitis in swine, to have complete 16S rDNA sequence identity and >70%
      DNA-DNA homology with human isolates within the M. fortuitum third biovariant
      complex. We identified 67 clinical and two environmental isolates of the M.
      fortuitum third biovariant sorbitol-negative group, of which 48 (70%) had the
      same PCR restriction enzyme analysis (PRA) profile as the hsp65 gene of M.
      porcinum (ATCC 33776(T)) and were studied in more detail. Most U.S. patient
      isolates were from Texas (44%), Florida (19%), or other southern coastal states
      (15%). Clinical infections included wound infections (62%), central catheter
      infections and/or bacteremia (16%), and possible pneumonitis (18%). Sequencing of
      the 16S rRNA gene (1,463 bp) showed 100% identity with M. porcinum ATCC 33776(T).
      Sequencing of 441 bp of the hsp65 gene showed four sequevars that differed by 2
      to 3 bp from the porcine strains. Clinical isolates were positive for
      arylsulfatase activity at 3 days, nitrate, iron uptake, D-mannitol, i-myo
      inositol, and catalase at 68 degrees C. They were negative for L-rhamnose and D
      glucitol (sorbitol). Clinical isolates were susceptible to ciprofloxacin,
      sulfamethoxazole, and linezolid and susceptible or intermediate to cefoxitin,
      clarithromycin, imipenem, and amikacin. M. porcinum ATCC 33776(T) gave similar
      results except for being nitrate negative. These studies showed almost complete
      phenotypic and molecular identity between clinical isolates of the M. fortuitum
      third biovariant D-sorbitol-negative group and porcine strains of M. porcinum and
      confirmed that they belong to the same species. Identification of M. porcinum
      presently requires hsp65 gene PRA or 16S rRNA or hsp65 gene sequencing.

PMID- 15583301
TI  - Varicella seroprevalence and molecular epidemiology of varicella-zoster virus in
      Argentina, 2002.
AB  - There is limited data on immunity against varicella-zoster virus (VZV) in adults
      in different parts of Argentina, and it is not known which VZV strains are
      circulating in Argentina. The objectives of this study were as follows: (i) to
      evaluate seroprevalence of varicella among adults, assessing the accuracy of
      clinical history and determining the sociodemographic factors associated with
      seropositivity; and (ii) to determine the VZV strains circulating in Argentina. A
      cross-sectional serological survey enrolling 2,807 women aged 15 to 49 years
      attending public health-care settings in four cities in Argentina (i.e., Buenos
      Aires, Salta, Mendoza, and Rosario) and one rural area was conducted from August
      to November 2002. Specimens for identification of VZV strains were obtained from
      vesicular lesions from 13 pediatric patients with varicella from different areas
      of the country. PCR amplification was used for genotyping. The overall
      seroprevalence of varicella antibodies was 98.5% (95% confidence interval, 98.0
      to 98.9), ranging from 97.2% in central Buenos Aires to 99.3% in southern Buenos
      Aires and Salta. Varicella seroprevalence increased with age. Crowding and length
      of residence in the same place were associated with seropositivity. The positive
      predictive value of varicella history for immunity to varicella was 99.4%;
      however, the negative predictive value was 2.5%. The European genotype was
      identified in all viral specimens. In Argentina, seroprevalence in women more
      than 15 years old was high regardless of the area of residence. Negative or
      uncertain varicella history was not a good predictor of immunity. VZV genotype
      was stable in all areas of the country.

PMID- 15583302
TI  - Detection of immunoglobulin M antibodies specific for Toxoplasma gondii with
      increased selectivity for recently acquired infections.
AB  - Toxoplasma gondii infections can cause serious complications in pregnant women,
      leading to miscarriage, stillbirth, and birth defects. Definitive diagnosis of T.
      gondii acute infection is therefore critical for the clinical management of a
      mother and her fetus. Positive immunoglobulin M (IgM) results are not sufficient
      as evidence of recent infection, as these antibodies are often present for many
      months. Further, IgG avidity and differential agglutination tests, two tests used
      by reference laboratories to distinguish between recent and past infections, are
      not always in agreement, and both methods yield a significant number of
      indeterminate results. We report the development of a new toxoplasma IgM
      immunoassay that is performed by using a bead-based immunoassay on an automated
      analyzer (BioPlex 2200). Initial validation included 204 samples from pregnant
      women and 198 samples from asymptomatic healthy adults. An overall specificity of
      99% was observed. Further, 100% sensitivity for acute infections was observed for
      10 well-characterized seroconversion panels. We then examined 50 samples from
      pregnant women, all of which were IgM positive by ELISA, which had been fully
      evaluated in a reference laboratory. Of the 50 samples, 34 (68%) tested positive
      in the BioPlex 2200 toxoplasma IgM assay, of which 32 of 34 (94%) exhibited an
      acute or equivocal pattern by differential agglutination. Of the 16 negative
      samples, 15 (94%) showed high-IgG-avidity antibodies. Collectively, these results
      suggest that this new toxoplasma assay shows a preferential response to IgM
      antibodies produced by recent infections, reducing the number of positive results
      for pregnant women that will require extensive additional clinical evaluation.

PMID- 15583303
TI  - Multiplex PCR targeting tpi (triose phosphate isomerase), tcdA (Toxin A), and
      tcdB (Toxin B) genes for toxigenic culture of Clostridium difficile.
AB  - A multiplex PCR toxigenic culture approach was designed for simultaneous
      identification and toxigenic type characterization of Clostridium difficile
      isolates. Three pairs of primers were designed for the amplification of (i) a
      species-specific internal fragment of the tpi (triose phosphate isomerase) gene,
      (ii) an internal fragment of the tcdB (toxin B) gene, and (iii) an internal
      fragment of the tcdA (toxin A) gene allowing distinction between toxin A
      positive, toxin B-positive (A+B+) strains and toxin A-negative, toxin B-positive
      (A-B+) variant strains. The reliability of the multiplex PCR was established by
      using a panel of 72 C. difficile strains including A+B+, A-B-, and A-B+ toxigenic
      types and 11 other Clostridium species type strains. The multiplex PCR assay was
      then included in a toxigenic culture approach for the detection, identification,
      and toxigenic type characterization of C. difficile in 1,343 consecutive human
      and animal stool samples. Overall, 111 (15.4%) of 721 human samples were positive
      for C. difficile; 67 (60.4%) of these samples contained A+B+ toxigenic isolates,
      and none of them contained A-B+ variant strains. Fifty (8%) of 622 animal samples
      contained C. difficile strains, which were toxigenic in 27 (54%) cases, including
      1 A-B+ variant isolate. Eighty of the 721 human stool samples (37 positive and 43
      negative for C. difficile culture) were comparatively tested by Premier Toxins
      A&B (Meridian Bioscience) and Triage C. difficile Panel (Biosite) immunoassays,
      the results of which were found concordant with toxigenic culture for 82.5 and
      92.5% of the samples, respectively. The multiplex PCR toxigenic culture scheme
      described here allows combined diagnosis and toxigenic type characterization for
      human and animal C. difficile intestinal infections.

PMID- 15583304
TI  - Phenotypic and molecular detection of CTX-M-beta-lactamases produced by
      Escherichia coli and Klebsiella spp.
AB  - Organisms producing CTX-M-beta-lactamases are emerging around the world as a
      source of resistance to oxyiminocephalosporins such as cefotaxime (CTX). However,
      the laboratory detection of these strains is not well defined. In this study, a
      molecular detection assay for the identification of CTX-M-beta-lactamase genes
      was developed and used to investigate the prevalence of these enzymes among
      clinical isolates of Escherichia coli and Klebsiella species in the Calgary
      Health Region during 2000 to 2002. In addition, National Committee for Clinical
      Laboratory Standards (NCCLS) recommendations were evaluated for the ability to
      detect isolates with CTX-M extended-spectrum beta-lactamases (ESBLs). The PCR
      assay consisted of four primer sets and demonstrated 100% specificity and
      sensitivity for detecting different groups of CTX-M-beta-lactamases in control
      strains producing well-characterized ESBLs. Using these primer sets, 175 clinical
      strains producing ESBLs were examined for the presence of CTX-M enzymes; 24 (14%)
      were positive for bla(CTX-M-1-like) genes, 95 (54%) were positive for bla(CTX-M
      14-like) genes, and the remaining 56 (32%) were negative for bla(CTX-M) genes.
      Following the NCCLS recommendations for ESBL testing, all of the control and
      clinical strains were detected when screened with cefpodoxime and when both
      cefotaxime and ceftazidime with clavulanate were used as confirmation tests.

PMID- 15583305
TI  - Variable number of tandem repeats in Salmonella enterica subsp. enterica for
      typing purposes.
AB  - The genomic sequences of Salmonella enterica subsp. enterica strains CT18, Ty2
      (serovar Typhi), and LT2 (serovar Typhimurium) were analyzed for potential
      variable number tandem repeats (VNTRs). A multiple-locus VNTR analysis (MLVA) of
      99 strains of S. enterica supsp. enterica based on 10 VNTRs distinguished 52
      genotypes and placed them into four groups. All strains tested were independent
      human isolates from France and did not reflect isolates from outbreak episodes.
      Of these 10 VNTRs, 7 showed variability within serovar Typhi, whereas 1 showed
      variability within serovar Typhimurium. Four VNTRs showed high Nei's diversity
      indices (DIs) of 0.81 to 0.87 within serovar Typhi (n = 27). Additionally, three
      of these more variable VNTRs showed DIs of 0.18 to 0.58 within serovar Paratyphi
      A (n = 10). The VNTR polymorphic site within multidrug-resistant (MDR) serovar
      Typhimurium isolates (n = 39; resistance to ampicillin, chloramphenicol,
      spectinomycin, sulfonamides, and tetracycline) showed a DI of 0.81. Cluster
      analysis not only identified three genetically distinct groups consistent with
      the present serovar classification of salmonellae (serovars Typhi, Paratyphi A,
      and Typhimurium) but also discriminated 25 subtypes (93%) within serovar Typhi
      isolates. The analysis discriminated only eight subtypes within serovar
      Typhimurium isolates resistant to ampicillin, chloramphenicol, spectinomycin,
      sulfonamides, and tetracycline, possibly reflecting the emergence in the mid
      1990s of the DT104 phage type, which often displays such an MDR spectrum. Coupled
      with the ongoing improvements in automated procedures offered by capillary
      electrophoresis, use of these markers is proposed in further investigations of
      the potential of MLVA in outbreaks of salmonellosis, especially outbreaks of
      typhoid fever.

PMID- 15583306
TI  - Phylogenetic analysis and PCR-restriction fragment length polymorphism
      identification of Campylobacter species based on partial groEL gene sequences.
AB  - The phylogeny of 12 Campylobacter species and reference strains of Arcobacter
      butzleri and Helicobacter pylori was studied based on partial 593-bp groEL gene
      sequences. The topology of the phylogenetic neighbor-joining tree based on the
      groEL gene was similar to that of the tree based on the 16S rRNA gene. However,
      groEL was found to provide a better resolution for Campylobacter species, with
      lower interspecies sequence similarities (range, 65 to 94%) compared with those
      for the 16S rRNA gene (range, 90 to 99%) and high intraspecies sequence
      similarities (range, 95 to 100%; average, 99%). A new universal reverse primer
      that amplifies a 517-bp fragment of the groEL gene was developed and used for PCR
      restriction fragment length polymorphism (PCR-RFLP) analysis of 68 strains
      representing 11 Campylobacter species as well as reference strains of A.
      butzlerii and H. pylori. Digestion with the AluI enzyme discriminated all
      Campylobacter species included in the study but showed more intraspecies
      diversity than digestion with the ApoI enzyme. A hippurate-negative variant of
      Campylobacter jejuni with a high level of groEL sequence similarity to both C.
      jejuni (96%) and C. coli (94%) gave a unique AluI profile and an ApoI profile
      identical to those of other C. jejuni strains. In conclusion, groEL gene
      sequencing and PCR-RFLP analysis are recommended as valuable tools for the
      identification of Campylobacter species.

PMID- 15583307
TI  - Simultaneous detection of Staphylococcus aureus and coagulase-negative
      staphylococci in positive blood cultures by real-time PCR with two fluorescence
      resonance energy transfer probe sets.
AB  - A real-time PCR assay that uses two fluorescence resonance energy transfer probe
      sets and targets the tuf gene of staphylococci is described here. One probe set
      detects the Staphylococcus genus, whereas the other probe set is specific for
      Staphylococcus aureus. One hundred thirty-eight cultured isolates, which
      contained 41 isolates of staphylococci representing at least nine species, and
      100 positive blood cultures that contained gram-positive cocci in clusters were
      tested. This assay was 100% sensitive and 100% specific for the detection of the
      Staphylococcus genus and of S. aureus.

PMID- 15583308
TI  - Diarrhea caused by rotavirus in children less than 5 years of age in Hanoi,
      Vietnam.
AB  - Group A rotaviruses are the major cause of diarrhea in young children worldwide.
      From March 2001 to April 2002, 836 children less than 5 years of age were
      investigated in Hanoi, Vietnam. This included 587 children with diarrhea and 249
      age-matched controls. Group A rotavirus was identified in 46.7% of the children
      with diarrhea and 3.6% of the controls, which was a significant difference.
      Within the diarrhea group, the highest prevalence was seen in children from 13 to
      24 months of age, and the prevalence was higher in males than in females. The
      symptoms of acute diarrhea caused by rotavirus were watery diarrhea, vomiting,
      fever, and dehydration. A higher prevalence of rotavirus detection was obtained
      for children who had all of these symptoms, followed by those who had diarrhea
      with vomiting-dehydration, fever-dehydration, and dehydration. The high rates
      occurred from September to December, although the infection was encountered all
      year round. In 58 patients (21.2% of the rotavirus-infected children), rotavirus
      infection was detected in association with either diarrheagenic Escherichia coli
      or Shigella spp. The most frequent combinations were rotavirus-enteroaggregative
      E. coli and rotavirus-enteropathogenic E. coli. At least one enteropathogen was
      identified from about 64% percent of the samples. The bacterial infection may not
      have given rise to clinical symptoms of such severity. The present study
      demonstrates the burden of rotavirus diarrhea in Hanoi, Vietnam. Continuous
      surveillance of diarrhea caused by rotavirus in young children would play an
      important role in diagnosis, treatment, and prophylaxis in order to improve the
      health of children in Vietnam.

PMID- 15583309
TI  - Direct comparison of the BD ProbeTec ET system with in-house LightCycler PCR
      assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae from
      clinical specimens.
AB  - The commercial BD ProbeTec ET (BDPT) system for the detection of Neisseria
      gonorrhoeae and Chlamydia trachomatis from clinical specimens was compared with
      our in-house LightCycler real-time PCR (LC-PCR) assays. Specimens initially
      positive by the BDPT system were retested by our LC-PCR assays. Our results for
      C. trachomatis testing indicate a 91.2% agreement when the results of 114
      clinical specimens, initially positive by BDPT over a wide range of method-other
      than-acceleration (MOTA) scores, were retested by our LC-PCR assay. The agreement
      between the two systems improved to 96% when only MOTA scores of >30,000 were
      retested by the LC-PCR assay. The overall agreement between the two systems for
      Neisseria gonorrhoeae detection from 155 clinical specimens was only 77.4%, with
      agreement particularly low (24.1%) for MOTA scores ranging from 2,000 to 19,999.
      Repeat testing of specimens with the BDPT only closely correlated with that seen
      by others demonstrating that reproducibility of the BDPT system for specimens
      initially within the MOTA score range from 2,000 to 9,999 is problematic,
      especially for Neisseria gonorrhoeae testing. With our study, we proposed an
      algorithm for C. trachomatis and N. gonorrhoeae testing which involves screening
      with the BDPT system followed by selective use of our in-house LC-PCR assays.

PMID- 15583310
TI  - Use of highly variable intergenic spacer sequences for multispacer typing of
      Rickettsia conorii strains.
AB  - By use of the nearly perfectly colinear genomes of Rickettsia conorii and
      Rickettsia prowazekii, we compared the usefulness of three types of sequences for
      typing of R. conorii isolates: (i) 5 variable coding genes comprising the 16S
      ribosomal DNA, gltA, ompB, and sca4 (gene D) genes, which are present in both
      genomes, and the ompA gene, which is degraded in R. prowazekii; (ii) 28 genes
      degraded in R. conorii but intact in R. prowazekii, including 23 split and 5
      remnant genes; and (iii) 27 conserved and 25 variable intergenic spacers. The 4
      conserved and 23 split genes as well as the 27 conserved intergenic spacers each
      had identical sequences in 34 human and 5 tick isolates of R. conorii. Analysis
      of the ompA sequences identified three genotypes of R. conorii. The variable
      intergenic spacers were significantly more variable than conserved genes, split
      genes, remnant genes, and conserved spacers (P < 10(-2) in all cases). Four of
      the variable intergenic spacers (dksA-xerC, mppA-purC, rpmE-tRNA(fMet), and
      tRNA(Gly)-tRNA(Tyr)) had highly variable sequences; when they were combined for
      typing, multispacer typing (MST) identified 27 different genotypes in the 39 R.
      conorii isolates. Two batches from the same R. conorii strain, Malish (Seven),
      with different culture passage histories were found to exhibit the same MST type.
      MST was more discriminatory for strain genotyping than multiple gene sequencing
      (P < 10(-2)). Phylogenetic analysis based on MST sequences was concordant with
      the geographic origins of R. conorii isolates. Our study supports the usefulness
      of MST for strain genotyping. This tool may be useful for tracing a strain and
      identifying its source during outbreaks, including those resulting from
      bioterrorism.

PMID- 15583311
TI  - Emergence of extended-spectrum-beta-lactamase (CTX-M-9)-producing multiresistant
      strains of Salmonella enterica serotype Virchow in poultry and humans in France.
AB  - During 2002 to 2003, eight Salmonella enterica serotype Virchow poultry and
      poultry product isolates from various sources (chicken farms, poultry
      slaughterhouse, or retail store) and one S. enterica rough strain isolated from
      human feces were found to produce extended-spectrum beta-lactamase CTX-M-9.
      Poultry and poultry product isolates were recovered from different locations in
      the southwest of France. The human rough isolate had sequences of flagellin genes
      (fliC and fljB) typical of serotype Virchow and ribotyping and pulsed-field gel
      electrophoresis (PFGE) patterns closely similar to those of serotype Virchow
      strains. PFGE confirmed the clonal relationship between the poultry isolates,
      while the human isolate displayed a pattern with 94% homology. The bla(CTX-M-9)
      gene was located on a conjugative plasmid and was shown to be linked to orf513.
      Plasmid profiling found a very similar EcoRI restriction pattern in six
      transconjugants studied, including transconjugants obtained from the human
      isolate. A single hatchery, supplying chicks to the six farms, was identified.
      Emergence of extended-spectrum beta-lactamase-producing S. enterica strains in
      food animals is a major concern, as such strains could disseminate on a large
      scale and lead to antibiotic therapy difficulties.

PMID- 15583312
TI  - Clonal expansion of a globally disseminated lineage of Mycobacterium tuberculosis
      with low IS6110 copy numbers.
AB  - Knowledge of the clonal expansion of Mycobacterium tuberculosis and accurate
      identification of predominant evolutionary lineages in this species remain
      limited, especially with regard to low-IS6110-copy-number strains. In this study,
      170 M. tuberculosis isolates with </=6 IS6110 insertions identified in Cape Town,
      South Africa, were characterized by principal genetic grouping, restriction
      fragment length polymorphism analysis, spoligotyping, IS6110 insertion site
      mapping, and variable-number tandem repeat (VNTR) typing. These analyses
      indicated that all but one of the isolates analyzed were members of principal
      genetic group 2 and of the same low-IS6110-copy-number lineage. The remaining
      isolate was a member of principal genetic group 1 and a different low-IS6110-copy
      number lineage. Phylogenetic reconstruction suggests clonal expansion through
      sequential acquisition of additional IS6110 copies, expansion and contraction of
      VNTR sequences, and the deletion of specific direct-variable-repeat sequences.
      Furthermore, comparison of the genotypic data of 91 representative low-IS6110
      copy-number isolates from Cape Town, other southern African regions, Europe, and
      the United States suggests that certain low-IS6110-copy-number strain
      spoligotypes and IS6110 fingerprints were acquired in the distant past. These
      clones have subsequently become widely disseminated and now play an important
      role in the global tuberculosis epidemic.

PMID- 15583313
TI  - Genome diversity of Pseudomonas aeruginosa isolates from cystic fibrosis patients
      and the hospital environment.
AB  - Pseudomonas aeruginosa is a gram-negative rod that is ubiquitous in nature. P.
      aeruginosa is also the quintessential opportunistic pathogen, causing a wide
      variety of infections in compromised hosts. In cystic fibrosis patients, P.
      aeruginosa is the leading cause of death. In this study, the evolutionary genetic
      relationships among 17 P. aeruginosa isolates were examined by comparative
      sequence analysis of the housekeeping gene encoding malate dehydrogenase and the
      chaperone groEL. The P. aeruginosa isolates examined included the sequenced
      strain PAO1, 11 strains recovered from cystic fibrosis patients in Ireland, 4
      environmental isolates recovered from a hospital environment, and 1 isolate
      recovered from a plant rhizosphere. Phylogenetically, clinical and environmental
      isolates clustered together with one another on the mdh gene tree. At the groEL
      locus, among the 17 isolates examined, only two polymorphic sites were observed,
      highlighting the close genetic relationship between isolates from these different
      environments. Phenotypic analysis of 12 traits among our isolates, however, found
      that only clinical isolates produced phenazines and elastase. Furthermore,
      molecular analysis of the distribution of 15 regions associated with virulence
      showed that two of the environmental isolates examined lacked the majority of
      regions. Among the clinical isolates examined, the 15 virulence regions were
      variably present. The distribution of two prophages (Bacto1, Pf1) was also
      determined, with most isolates encoding both these regions. Of the four genomic
      islands (the flagellum island and PAGI-1, -2, and -3) examined, only two isolates
      contained the flagellum island, and PAGI-1, -2, and -3 were absent from all
      isolates tested. Our data demonstrate the significant role horizontal gene
      transfer and recombination, together with gene loss, play in the evolution of
      this important human pathogen.

PMID- 15583314
TI  - Mapping of genomic segments of influenza B virus strains by an oligonucleotide
      microarray method.
AB  - Similar to other segmented RNA viruses, influenza viruses can exchange genome
      segments and form a wide variety of reassortant strains upon coreplication within
      a host cell. Therefore, the mapping of genome segments of influenza viruses is
      essential for understanding their phenotypes. In this work, we have developed an
      oligonucleotide microarray hybridization method for simultaneous genotyping of
      all genomic segments of two highly homologous strains of influenza B virus. A few
      strain-specific oligonucleotide probes matching each of the eight segments of the
      viral genomes of the B/Beijing/184/93 and B/Shangdong/7/97 strains were
      hybridized with PCR-amplified fluorescently labeled single-stranded DNA. Even
      though there were a few mismatches among the genomes of the studied virus
      strains, microarray hybridization showed highly significant and reproducible
      discrimination ability and allowed us to determine the origins of individual
      genomic segments in a series of reassortant strains prepared as vaccine
      candidates. Additionally, we were able to detect the presence of at least 5% of
      mixed genotypes in virus stocks even when conventional sequencing methods failed,
      for example, for the NS segment. Thus, the proposed microarray method can be used
      for (i) rapid and reliable genome mapping of highly homologous influenza B
      viruses and (ii) extensive monitoring of influenza B virus reassortants and the
      mixed genotypes. The array can be expanded by adding new oligoprobes and using
      more quantitative assays to determine the origin of individual genomic segments
      in series of reassortant strains prepared as vaccine candidates or in mixed virus
      populations.

PMID- 15583315
TI  - Surface immunoglobulin-deficient Epstein-Barr virus-infected B cells in the
      peripheral blood of pediatric solid-organ transplant recipients.
AB  - Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, normally causes an
      asymptomatic latent infection with very low levels of circulating virus in the
      peripheral blood of infected individuals. However, EBV does have pathogenic
      potential and has been linked to several diseases, including posttransplant
      lymphoproliferative disease (PTLD), which involves very high circulating viral
      loads. As a consequence of immunosuppression associated with transplantation,
      children in particular are at risk for PTLD. Even in the absence of symptoms of
      PTLD, very high viral loads are often observed in these patients. EBV-infected B
      cells in the circulations of 16 asymptomatic pediatric solid-organ transplant
      recipients from Children's Hospital of Pittsburgh were simultaneously
      characterized for their surface immunoglobulin (sIg) isotypes and EBV genome copy
      numbers. Patients were characterized as having high and low viral loads on the
      basis of their stable levels of circulating virus. Patients with high viral loads
      had both high- and low-copy-number cells. Cells with a high numbers of viral
      episomes (>20/cell) were predominantly Ig null, and cells with low numbers of
      episomes were predominantly sIgM positive. Patients with low viral loads carried
      the vast majority of their viral load in low-copy-number cells, which were
      predominantly IgM positive. The very rare high-copy-number cells detected in
      carriers with low viral loads were also predominantly Ig-null cells. This
      suggests that two distinct types of B-lineage cells contribute to the viral load
      in transplant recipients, with cells bearing high genome copy numbers having an
      aberrant Ig-null cellular phenotype.

PMID- 15583316
TI  - DNA microarrays for virus detection in cases of central nervous system infection.
AB  - A low-density, high-resolution diagnostic DNA microarray comprising 38 gene
      targets for 13 viral causes of meningitis and encephalitis was constructed. The
      array has been used for the detection of multiplex PCR-amplified viruses in
      cerebrospinal fluid (CSF) and non-CSF specimens. A total of 41 clinical specimens
      were positive for echoviruses (23 samples), herpes simplex virus type 2 (4
      samples), varicella-zoster virus (4 samples), human herpesvirus 7 (1 sample),
      human herpesvirus 6A (1 sample) and 6B (2 samples), Epstein-Barr virus (three
      samples), polyomavirus JC (1 sample), and cytomegalovirus (2 samples). Probes for
      herpes simplex virus type 1, polyomavirus BK, and mumps and measles viruses were
      also included on the array. Three samples were false negative by the microarray
      assay due to discordant results between the multiplex PCR for all 13 viruses
      simultaneously and the virus-specific PCR alone. Fifteen CSF specimens were true
      negative. The clinical sensitivity, specificity, and negative and positive
      predictive values of the assay were 93, 100, 100, and 83%, respectively, when the
      results were compared to those of the single-virus PCR, which was used as the
      "gold standard." The microarray-based virus detection assay is qualitative and
      provides a single-format diagnostic tool for the detection of panviral CNS
      infections.

PMID- 15583317
TI  - Detection of gyrA and parC mutations associated with ciprofloxacin resistance in
      Neisseria gonorrhoeae by use of oligonucleotide biochip technology.
AB  - An oligonucleotide biochip that specifically detects point mutations in the gyrA
      and parC genes of Neisseria gonorrhoeae was designed and subsequently evaluated
      with 87 untreated clinical specimens. The susceptibilities of the N. gonorrhoeae
      strains were tested to determine the prevalence of ciprofloxacin-resistant
      strains in Anhui Province, People's Republic of China. Conventional DNA
      sequencing was also performed to identify mutations in gyrA and parC and to
      confirm the biochip data. The study demonstrates that all of the point mutations
      in the gyrA and parC genes of N. gonorrhoeae were easily discriminated by use of
      the oligonucleotide biochip. Fifteen different alteration patterns involved in
      the formation of ciprofloxacin resistance were identified by the biochip assay.
      Double mutations in both Ser91 and Asp95 of the GyrA protein were seen in all
      nonsensitive isolates. Double mutations in Ser91 and Asp95 of GyrA plus mutation
      of Glu91 or Ser87 of the ParC protein lead to significant high-level resistance
      to ciprofloxacin in N. gonorrhoeae isolates. The results obtained by use of the
      oligonucleotide biochip were identical to those obtained by use of DNA
      sequencing. In conclusion, the oligonucleotide biochip technology has potential
      utility for the rapid and reliable identification of point mutations in the drug
      resistance genes of N. gonorrhoeae.

PMID- 15583318
TI  - Real-time PCR assay for a unique chromosomal sequence of Bacillus anthracis.
AB  - Real-time PCR has become an important method for the rapid identification of
      Bacillus anthracis since the 2001 anthrax mailings. Most real-time PCR assays for
      B. anthracis have been developed to detect virulence genes located on the pXO1
      and pXO2 plasmids. In contrast, only two published chromosomal targets exist, the
      rpoB gene and the gyrA gene. In the present study, subtraction-hybridization with
      a plasmid-cured B. anthracis tester strain and a Bacillus cereus driver was used
      to find a unique chromosomal sequence. By targeting this region, a real-time
      assay was developed with the Ruggedized Advanced Pathogen Identification Device.
      Further testing has revealed that the assay has 100% sensitivity and 100%
      specificity, with a limit of detection of 50 fg of DNA. The results of a search
      for sequences with homology with the BLAST program demonstrated significant
      alignment to the recently published B. anthracis Ames strain, while an inquiry
      for protein sequence similarities indicated homology with an abhydrolase from B.
      anthracis strain A2012. The importance of this chromosomal assay will be to
      verify the presence of B. anthracis independently of plasmid occurrence.

PMID- 15583319
TI  - Construction strategy for an internal amplification control for real-time
      diagnostic assays using nucleic Acid sequence-based amplification: development
      and clinical application.
AB  - An important analytical control in molecular amplification-based methods is an
      internal amplification control (IAC), which should be included in each reaction
      mixture. An IAC is a nontarget nucleic acid sequence which is coamplified
      simultaneously with the target sequence. With negative results for the target
      nucleic acid, the absence of an IAC signal indicates that amplification has
      failed. A general strategy for the construction of an IAC for inclusion in
      molecular beacon-based real-time nucleic acid sequence-based amplification
      (NASBA) assays is presented. Construction proceeds in two phases. In the first
      phase, a double-stranded DNA molecule that contains nontarget sequences flanked
      by target sequences complementary to the NASBA primers is produced. At the 5' end
      of this DNA molecule is a T7 RNA polymerase binding sequence. In the second phase
      of construction, RNA transcripts are produced from the DNA by T7 RNA polymerase.
      This RNA is the IAC; it is amplified by the target NASBA primers and is detected
      by a molecular beacon probe complementary to the internal nontarget sequences. As
      a practical example, an IAC for use in an assay for the detection of
      Mycobacterium avium subsp. paratuberculosis is described, its incorporation and
      optimization within the assay are detailed, and its application to spiked and
      natural clinical samples is shown to illustrate the correct interpretation of the
      diagnostic results.

PMID- 15583320
TI  - Clinical and serological variation between patients infected with different
      Hepatitis B virus genotypes.
AB  - Hepatitis B virus (HBV) has eight genotypes which have distinct geographical
      distributions. Studies comparing differences in the clinical outcomes of
      infections caused by strains with genotype-related variations in the HBV genome
      have largely compared genotypes B and C and genotypes A and D but not all four
      genotypes. The present study included 196 HBV-infected patients attending an
      infectious diseases outpatient clinic in Sweden. The age and geographic origin,
      liver function, HBeAg and anti-HBe status, and the presence or absence of HBV DNA
      were analyzed for each patient. HBV DNA was detected in 144 patients, and the HBV
      genotype and the core promoter and precore sequences were determined for the
      isolates from 101 of these patients. Among the patients who might be considered
      most likely to be nonviremic, namely, anti-HBe-positive HBV carriers with normal
      alanine aminotransferase (ALT) levels, 65% had detectable HBV DNA and were thus
      viremic. Among the viremic patients, HBeAg-positive patients were more likely to
      have elevated ALT levels than anti-HBe-positive patients. HBV genotypes A to F
      were represented in the study, and their distributions coincided accurately with
      the origin of the patient. A significantly higher number of genotype D-infected
      patients were anti-HBe positive and had elevated ALT levels (42% of genotype D
      infected patients but 0% of patients infected with genotypes B and C). Genotype D
      strains with mutations in the core promoter and precore regions were
      significantly correlated with elevated ALT levels in the patients. The
      differences were not age related. Therefore, in this large-scale cross-sectional
      study, genotype D appears to be associated with more active disease.

PMID- 15583321
TI  - Azithromycin retards Pseudomonas aeruginosa biofilm formation.
AB  - Using a flow cell biofilm model, we showed that a sub-MIC of azithromycin (AZM)
      can delay but not inhibit Pseudomonas aeruginosa biofilm formation and results in
      the development of a stable AZM resistance phenotype. Furthermore, mature
      biofilms were not affected by AZM.

PMID- 15583322
TI  - Comparison of antifungal susceptibilities to fluconazole and voriconazole of oral
      Candida glabrata isolates from head and neck radiation patients.
AB  - The antifungal susceptibilities of 79 oral Candida glabrata isolates to
      fluconazole and voriconazole were compared. The MICs at which 90% of the isolates
      tested were inhibited were 1 microg of voriconazole/ml and 32 microg of
      fluconazole/ml. Oral C. glabrata isolates for which the fluconazole MICs are
      elevated are commonly those for which the voriconazole MICs are elevated, but
      these increases may be transient for voriconazole, as they are for fluconazole.

PMID- 15583323
TI  - Evaluation of multiplex PCRs for diagnosis of infection with diarrheagenic
      Escherichia coli and Shigella spp.
AB  - We have developed two multiplex PCR assays that detect typical and atypical
      enteropathogenic Escherichia coli (EPEC) isolates, enteroaggregative E. coli
      (EAEC) isolates, enterotoxigenic E. coli (ETEC) isolates, enteroinvasive E. coli
      (EIEC) isolates, Shiga toxin-producing E. coli (STEC) isolates, and Shigella spp.
      The targets selected for each group were eae and bfpA for EPEC isolates, the
      target of probe CVD432 for EAEC isolates, the genes encoding heat-labile and heat
      stable toxins for ETEC isolates, stx(1) and stx(2) for STEC isolates, and ipaH
      for EIEC isolates and Shigella spp. These PCRs were specific and sensitive for
      rapid detection of target isolates in stools. Among 150 stool specimens from the
      acute diarrhea tested, 9 samples (6%) had atypical EPEC, 9 (6%) had typical EPEC,
      7 (4.7%) had EAEC, 3 (2%) had EIEC, 3 (2%) had Shigella spp., and 1 (0.7%) had an
      O26 STEC strain; we also detected mixed infections, 2 (1.3%) with EAEC and
      Shigella spp., 1 (0.7%) with atypical and typical EPEC strains, and another with
      atypical EPEC and EAEC strains. One of the multiplex PCRs directly applied to 36
      stool specimens correctly identified 100% of EPEC and EAEC isolates.

PMID- 15583324
TI  - Diverse CTX phages among toxigenic Vibrio cholerae O1 and O139 strains isolated
      between 1994 and 2002 in an area where cholera is endemic in Bangladesh.
AB  - PCR surveillance of the rstR genes of CTX phages in Vibrio cholerae O1 and O139
      showed no relationship between the incidence of disease and changes in the rstR
      but showed variations in their presence in O1 and O139 strains and the occurrence
      of multiple types in a few strains.

PMID- 15583325
TI  - Detection of the van alphabet and identification of enterococci and staphylococci
      at the species level by multiplex PCR.
AB  - A multiplex PCR assay was developed for detection of the six types of
      glycopeptide resistance characterized in enterococci and for identification of
      Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, and
      Staphylococcus epidermidis at the species level. Primers targeting the genes
      vanA, vanB, vanC, vanD, vanE, vanG, and ddl of E. faecium and E. faecalis and nuc
      of S. aureus and a chromosomal portion specific to S. epidermidis were designed
      to allow amplification of fragments with various sizes. This specific and
      sensitive technique allows detection of glycopeptide-resistant strains, in
      particular methicillin-resistant S. aureus, that may escape phenotype-based
      automated rapid methods.

PMID- 15583326
TI  - High permissivity of human HepG2 hepatoma cells for influenza viruses.
AB  - Human HepG2 hepatoma cells are highly permissive for influenza virus type A and
      type B, even without the addition of trypsin, and they exhibit a marked
      cytopathic effect. This property greatly facilitates the primary isolation of
      influenza viruses. Virus replication was significantly reduced by the
      plasmin(ogen)-specific inhibitor tranexamic acid, and this suggests a potential
      role played by the plasminogen/tissue plasminogen activator complex at the
      surface of HepG2 cells. This might represent a new approach for study of the
      interrelations of this complex with influenza viruses.

PMID- 15583327
TI  - Rapid discrimination between human immunodeficiency virus type 2 groups A and B
      by real-time PCR.
AB  - We studied the feasibility of genotyping human immunodeficiency virus (HIV) type
      2 groups A and B by real-time PCR. Two group-specific PCRs were developed. Real
      time genotyping of 22 samples of genotype A, 10 samples of genotype B, and the
      isolate of new group H were compared to genotyping by sequencing and phylogeny.
      The group-specific PCRs specifically identified 84.3% of group A or B samples;
      isolate H was not detected. This method allowed rapid and specific discrimination
      between HIV-2 groups A and B and could be a useful tool for molecular
      epidemiological studies.

PMID- 15583328
TI  - Identification and discrimination of Burkholderia pseudomallei, B. mallei, and B.
      thailandensis by real-time PCR targeting type III secretion system genes.
AB  - Burkholderia pseudomallei and B. mallei are two highly pathogenic bacteria,
      responsible for melioidosis and glanders, respectively. The two are closely
      related and can also be mistaken for B. thailandensis, a nonpathogenic species.
      To improve their differential identification, we describe a hydrolysis probe
      based real-time PCR method using the uneven distribution of type III secretion
      system genes among these three species.

PMID- 15583329
TI  - Evaluation of decontamination methods and growth media for primary isolation of
      Mycobacterium ulcerans from surgical specimens.
AB  - We evaluated four decontamination methods and one nondecontamination procedure in
      combination with four egg-based media for the primary isolation of Mycobacterium
      ulcerans from tissue specimens. With mycobacterial recovery and contamination
      rates of 75.6 and 2.4%, respectively, the combination of the oxalic acid
      decontamination method with Lowenstein-Jensen medium supplemented with glycerol
      yielded the best results.

PMID- 15583330
TI  - Broth microdilution susceptibility testing of Francisella tularensis: quality
      control limits for nine antimicrobial agents and three standard quality control
      strains.
AB  - For broth microdilution susceptibility tests of Francisella tularensis, Mueller
      Hinton broth with 2% Isovitalex is recommended. Using that medium, we studied
      three standard control strains tested with nine antimicrobial agents potentially
      efficacious for treating tularemia. An eight-laboratory collaborative study
      generated the data needed to propose appropriate MIC control limits.

PMID- 15583331
TI  - Clinical isolates of Staphylococcus intermedius masquerading as methicillin
      resistant Staphylococcus aureus.
AB  - Staphylococcus intermedius is a zoonotic organism that can be associated with
      human disease. We report two separate cases of S. intermedius infection in which
      a false-positive rapid penicillin binding protein 2a latex test in conjunction
      with the phenotypic properties of beta-hemolysis and coagulase positivity allowed
      the clinical isolates to masquerade as methicillin-resistant Staphylococcus
      aureus. 16S rRNA gene sequencing and the absence of mecA revealed the strains to
      be methicillin-susceptible S. intermedius.

PMID- 15583332
TI  - False-positive results in a recombinant severe acute respiratory syndrome
      associated coronavirus (SARS-CoV) nucleocapsid enzyme-linked immunosorbent assay
      due to HCoV-OC43 and HCoV-229E rectified by Western blotting with recombinant
      SARS-CoV spike polypeptide.
AB  - Using paired serum samples obtained from patients with illness associated with
      increases in anti-human coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E
      antibodies, we examined the possibility of false-positive results detected in a
      recombinant severe acute respiratory syndrome (SARS)-associated coronavirus (SARS
      CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay
      (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from
      persons with increases in antibodies against HCoV-OC43 and HCoV-229E,
      respectively, tested positive by the recombinant SARS-CoV nucleocapsid protein
      based ELISA. None of these samples were found to contain a specific antibody in
      the recombinant SARS-CoV spike polypeptide-based Western blot assay.

PMID- 15583333
TI  - Comparison of PCR- and HinfI restriction endonuclease-based methods for typing of
      Candida krusei isolates.
AB  - We compared HinfI restriction endonuclease-based analysis of genomic DNA with a
      PCR-based method for molecular typing of 90 Candida krusei isolates from 17
      geographically related patients. Strain groupings by these methods were the same
      for 89 of 90 isolates. Ten of 17 patients were infected with related strains of
      C. krusei.

PMID- 15583334
TI  - Use of species-directed 16S rRNA gene PCR primers for detection of Atopobium
      vaginae in patients with bacterial vaginosis.
AB  - Recent studies suggest that the association between a metronidazole-resistant
      anaerobe, Atopobium vaginae, and bacterial vaginosis (BV) warrants further
      investigation. In the present study, specific primers enhanced detection of A.
      vaginae and provided additional evidence that this bacterium is prevalent among
      patients with BV but absent among patients with normal vaginal flora.

PMID- 15583335
TI  - Vancomycin resistance, esp, and strain relatedness: a 1-year study of
      enterococcal bacteremia.
AB  - The prevalence of esp, a gene associated with infection-derived and outbreak
      strains, in enterococcal blood isolates from 2002 was determined. Fifty-five of
      137 (40.1%) Enterococcus faecalis isolates, 30 of 58 (51.7%) E. faecium isolates,
      1 of 1 E. raffinosus isolate, 0 of 4 E. gallinarum isolates, and 0 of 1 E.
      casseliflavus isolate were positive. esp wasn't associated with vancomycin
      resistance (VR) or clinical service. VR E. faecium isolates were less genetically
      diverse than vancomycin-susceptible strains. A large cluster of VR isolates,
      belonging to esp-positive E. faecium, was revealed. These data support the
      hypothesis that esp and VR may contribute to dissemination of particular clones.

PMID- 15583336
TI  - Study of molecular epidemiology of candidiasis in portugal by PCR fingerprinting
      of Candida clinical isolates.
AB  - PCR fingerprinting was used to type 177 yeast isolates obtained from two medical
      institutions. Candida albicans was the predominant species found, followed by C.
      tropicalis, C. glabrata, C. parapsilosis, C. guilliermondii, and C. krusei, which
      accounted for over 20% of the strains isolated. This survey represents the first
      study of molecular epidemiology of candidiasis in Portugal.

PMID- 15583337
TI  - Characterization of hemolytic Escherichia coli strains in ferrets: recognition of
      candidate virulence factor CNF1.
AB  - Diseases associated with Escherichia coli infection are the subject of renewed
      interest due to emerging conditions such as hemolytic uremia syndrome. A
      collection of 15 strains of beta-hemolytic E. coli was isolated from diarrheic
      feces and diseased tissues of ferrets. All 15 strains were positive in specific
      PCR assays for the presence of hlyA, pap1, and cnf1. Seven of the cnf1-positive
      isolates were tested and shown to have a cytopathic effect on HeLa cell
      monolayers. The pathogenesis of these strains warrants future study.

PMID- 15583338
TI  - Identification of a novel mycoplasma species from an Oriental white-backed
      vulture (Gyps bengalensis).
AB  - An intracellular organism was isolated from the tissues of an Oriental white
      backed vulture (Gyps bengalensis) in chicken embryo fibroblast cell cultures.
      Biochemical and physical properties, ultrastructural features, and 16S ribosomal
      DNA sequencing classified this organism as a new taxon of mycoplasma, for which
      the name "Mycoplasma vulturii" is proposed.

PMID- 15583339
TI  - Comparison of five methods for extraction of Legionella pneumophila from
      respiratory specimens.
AB  - The efficiencies of five commercially available nucleic acid extraction methods
      were evaluated for the recovery of a standardized inoculum of Legionella
      pneumophila in respiratory specimens (sputum and bronchoalveolar lavage [BAL]
      specimens). The concentrations of Legionella DNA recovered from sputa with the
      automated MagNA Pure (526,200 CFU/ml) and NucliSens (171,800 CFU/ml) extractors
      were greater than those recovered with the manual methods (i.e., Roche High Pure
      kit [133,900 CFU/ml], QIAamp DNA Mini kit [46,380 CFU/ml], and ViralXpress kit
      [13,635 CFU/ml]). The rank order was the same for extracts from BAL specimens,
      except that for this specimen type the QIAamp DNA Mini kit recovered more than
      the Roche High Pure kit.

PMID- 15583340
TI  - Molecular epidemiological analysis of Escherichia coli isolates producing
      extended-spectrum beta-lactamases for identification of nosocomial outbreaks in
      Stockholm, Sweden.
AB  - From June to October of 2002, a cluster of Escherichia coli isolates producing
      extended-spectrum beta-lactamases (ESBLs) was detected in Stockholm. The isolates
      were grouped into two clones, one of which had already circulated in the same
      area before the outbreak. CTX-M-type ESBLs and coresistance to ciprofloxacin were
      identified in the strains.

PMID- 15583341
TI  - Clinical evaluation of the gen-probe amplified mycobacterium tuberculosis direct
      test for rapid diagnosis of tuberculosis lymphadenitis.
AB  - This prospective study evaluated the performance of the Amplified Mycobacterium
      Tuberculosis Direct Test (MTD) for the diagnosis of lymph node tuberculosis in
      Djibouti, Republic of Djibouti. Of 197 specimens sampled from 153 patients, 123
      were from 95 tuberculous patients. The sensitivity and specificity of MTD were 93
      and 100%, respectively. The sensitivity of culture was 89%.

PMID- 15583342
TI  - Histidine decarboxylase in Enterobacteriaceae revisited.
AB  - With a modification of Taylor's decarboxylation broth, histidine decarboxylase
      was detected in Enterobacter aerogenes, Morganella morganii, Raoultella
      ornithinolytica, and some strains of Citrobacter youngae and Raoultella
      planticola. This method provides a useful confirmatory test for identification of
      E. aerogenes strains.

PMID- 15583343
TI  - Differential recovery of Candida species from subgingival sites in human
      immunodeficiency virus-positive and healthy children from Rio de Janeiro, Brazil.
AB  - The prevalence of subgingival Candida species was studied in 52 human
      immunodeficiency virus (HIV)-positive and 42 HIV-negative children. Candida was
      cultured from 22 (42.3%) and 3 (7.1%) HIV-infected and control children,
      respectively. C. albicans was the most common Candida species isolated from HIV
      infected children, followed by C. dubliniensis, C. glabrata, and C. tropicalis.
      In the HIV-positive group, the prevalence of Candida isolation was significantly
      higher in children who presented with low CD4(+)-T-lymphocyte counts, elevated
      viral loads, and gingivitis.

PMID- 15583344
TI  - Detection of resistance to gatifloxacin and moxifloxacin in Streptococcus
      pneumoniae with the VITEK 2 instrument.
AB  - A group of 72 pneumococcal isolates resistant or intermediate to levofloxacin and
      124 pneumococcal isolates susceptible to fluoroquinolones were tested by the
      VITEK 2 instrument using investigational test cards and by a broth microdilution
      reference method. The VITEK 2 instrument performed well, detecting 52 of 60
      (86.7%) gatifloxacin-resistant isolates and 22 of 23 moxifloxacin-resistant
      isolates, and did not falsely classify any susceptible isolates as resistant.

PMID- 15583345
TI  - Conventional and molecular epidemiology of tuberculosis in homeless patients in
      Budapest, Hungary.
AB  - In Hungary the incidence of tuberculosis among the homeless population was 676
      per 100,000 in 2002. Sixty-nine percent (140 patients) of all homeless
      tuberculosis patients were notified in Budapest (the capital). Therefore, a
      retrospective study that included 66 homeless tuberculosis patients notified in
      Budapest in 2002 was conducted to determine the rate of recent transmission of
      the disease and medical risk factors and to identify transmission pathways by
      means of conventional and molecular epidemiologic methods. IS6110 DNA
      fingerprinting revealed that 71.2% of the isolates could be clustered. Thirty
      four (51.5%) patients belonged to five major clusters (size, from 4 to 11
      individuals), and 13 (19.7%) belonged to six smaller clusters. Additional
      analysis of patient records found that 2 (18%) of the 11 patients in cluster A, 3
      (37.5%) of the 8 patients in cluster B, and 2 (33%) of the 6 patients in cluster
      C were residents of the same three homeless shelters during the diagnosis of
      tuberculosis. Review of the database of the National Tuberculosis Surveillance
      Center (NTSC) revealed that 21.2% of the cases have not been reported to the
      NTSC. These findings indicate that the screening and treatment of tuberculosis
      among the homeless need to be strengthened and also warrant the review of
      environmental control steps in public shelters. Improvement of adherence of
      clinicians to surveillance reporting regulations is also necessary.

PMID- 15583346
TI  - Development and evaluation of fluorogenic TaqMan reverse transcriptase PCR assays
      for detection of dengue virus types 1 to 4.
AB  - The fluorogenic TaqMan reverse transcriptase PCR (RT-PCR) assay was developed for
      detecting each of the dengue virus (DV) types 1 to 4. DV genome was detected in
      all the 35 serum samples from confirmed dengue cases by the TaqMan RT-PCR,
      although it was not detected in 13 and 21% by conventional type-specific and
      cross-reactive RT-PCR, respectively.

PMID- 15583347
TI  - Molecular characterization of fluconazole resistance in a case of Candida
      albicans ocular infection.
AB  - Ocular yeast infections in diabetics are a therapeutic challenge. Drug resistance
      and reduced azole susceptibility are major concerns. The case we describe
      characterizes a Candida albicans strain from a vitrectomy specimen that was
      susceptible to fluconazole by in vitro testing but recalcitrant to therapy.
      Molecular studies revealed transient overexpression of CDR1 and ERG11 mRNA in the
      presence of fluconazole that may have contributed to poor clinical response in
      this patient.

PMID- 15583348
TI  - Peripartum bacteremias due to Leptotrichia amnionii and Sneathia sanguinegens,
      rare causes of fever during and after delivery.
AB  - We report three cases of delivery and postpartum bacteremia due to unusual
      anaerobic bacteria in healthy young women. Leptotrichia amnionii bacteremia
      occurred during delivery in two mothers and was associated with fetal distress
      during labor. Conversely, Sneathia sanguinegens bacteremia occurred postpartum, 2
      days after delivery, without consequence for the neonate.

PMID- 15583349
TI  - Early reinfection with human metapneumovirus in an infant.
AB  - Human metapneumovirus (hMPV) is one of the major pathogens of respiratory
      illness. Reinfection with hMPV occurs frequently throughout life. We describe an
      infant who was infected with two different hMPV strains during a period of only 1
      month.

PMID- 15583350
TI  - Bacteremia due to Clostridium hathewayi in a patient with acute appendicitis.
AB  - Clostridium hathewayi is a newly described Clostridium species isolated from the
      feces of healthy human individuals, but its clinical significance is not known.
      We describe a case of human infection associated with C. hathewayi. The bacterium
      (strain HKU18) was isolated from the blood culture of a 39-year-old patient with
      acute gangrenous appendicitis complicated by septic shock. The cells were
      strictly anaerobic, nonmotile rods that stained gram negative. Conventional
      phenotypic tests and commercial identification systems failed to identify HKU18
      to the species level. 16S rRNA gene analysis showed 1.4% nucleotide difference
      between the sequence of HKU18 and that of C. hathewayi, indicating that HKU18 was
      a strain of C. hathewayi. The patient responded to appendectomy and antibiotic
      treatment. 16S rRNA gene sequencing would be useful in further characterizing the
      clinical disease spectrum of C. hathewayi.

PMID- 15583351
TI  - Refractory candidal meningitis in an immunocompromised patient cured by
      caspofungin.
AB  - Candidal meningitis is a rare infectious disease that usually leads to
      substantial morbidity and mortality. We present a case of candidal meningitis
      refractory to systemic antifungal therapy (amphotericin B and fluconazole). A 63
      year-old female with lymphoblastic lymphoma and myelodysplasia with leukemia
      transformation developed prolonged fever and headache on the seventh day
      following intrathecal prophylactic chemotherapy. A lumbar puncture showed
      neutrophilic pleocytosis, and a cerebrospinal fluid culture yielded Candida
      albicans. The clinical course was complicated by brain edema, subarachnoid
      hemorrhage, and hydrocephalus. Parenteral therapy with amphotericin B alone or
      amphotericin B in combination with fluconazole or intrathecal administration of
      amphotericin B failed to eradicate C. albicans in the cerebrospinal fluid. After
      7 days of caspofungin therapy, however, the cerebrospinal fluid became sterile
      and the patient gradually regained consciousness. She was discharged 1 month
      after completing 4 weeks of caspofungin therapy. There were two critical issues
      we thought to be relevant to the favorable outcome of this case. First, isolation
      of C. albicans was achieved by inoculating enriched liquid medium with
      cerebrospinal fluid. Second, there is a potential therapeutic benefit of
      caspofungin in treating a fungal infection of the central nervous system.

PMID- 15583352
TI  - Usefulness of PCR analysis for diagnosis of alveolar echinococcosis with unusual
      localizations: two case studies.
AB  - The report presents two cases where diagnosis of alveolar echinococcosis was
      confirmed by Echinococcus multilocularis and Echinococcus granulosus PCR. The
      extrahepatic osseous involvement and the absence of initial hepatic involvement
      are unusual in both cases. Due to limitations of serological interpretation, PCR
      was useful to diagnose atypical echinococcosis.

PMID- 15583353
TI  - Streptomyces albus isolated from a human actinomycetoma and characterized by
      molecular techniques.
AB  - A Streptomyces albus forearm actinomycetoma that could not be identified by
      culture was properly identified at the species level by study of an internal
      fragment of the heat shock protein gene, comparative sequence analysis of 16S
      ribosomal DNA (rDNA), and the hypervariable gamma-region of the 16S rDNA.

PMID- 15583354
TI  - First detection of human metapneumovirus in children with acute respiratory
      infection in India: a preliminary report.

PMID- 15583355
TI  - Impact of clinical practice guidelines on the clinical microbiology laboratory
      when using automated blood culture systems for bacterial contamination screening
      of apheresis platelet products.

PMID- 15583356
TI  - Finding reviewers electronically.

PMID- 15583357
TI  - Dentate gyrus neurogenesis after cerebral ischemia and behavioral training.
AB  - Neurogenesis in the mammalian brain continues throughout adulthood. Several
      factors have been shown to influence neurogenesis, including experience in a
      complex environment (EC), exercise (EX), and ischemic insult. The authors
      investigated the effects of behavioral rehabilitation training following
      transient global cerebral ischemia on the number of new cells in the dentate
      gyrus that incorporated bromodeoxyuridine (BrdU), a thymidine analog that labels
      cells undergoing DNA replication. Seventy-two animals were included in the study,
      and 4-vessel occlusion was used to induce cerebral ischemia while control animals
      were subjected to anesthesia and sham surgery alone. Within 3 days of surgery,
      rats were randomly assigned to either EC, EX, or control (paired housing in
      standard laboratory conditions) groups. All animals were sacrificed 2 weeks after
      behavioral training. Immunohistochemistry results showed an increased number of
      BrdU-labeled cells in the subgranular zone of the dentate gyrus in all ischemic
      groups and in the EC and EX sham groups, although no significant group
      differences were seen. Examination of cell phenotype showed that almost all BrdU
      positive cells colabeled with TuJ1, an immature neuron marker, in all animals
      whereas only a few BrdU-positive cells colabeled with NeuN, a mature neuron
      marker. BrdU/NeuN-labeled cells were seen only in the sham and ischemia EC
      groups. No new cells showed glial fibrillary acidic protein, astrocyte marker,
      colabeling. These results suggest that the adult brain has an inherent
      regenerative capacity after insult and that behavioral training following injury
      does not have an additive effect on neurogenesis. Finally, the enhanced
      maturation of BrdU-positive cells seen in the EC rats is probably modulated by
      environmental cues.

PMID- 15583358
TI  - Comparison of a visual to a computer-assisted technique for detecting apoptosis.
AB  - In many studies, fluorescent dyes (ethidium bromide [EB] and acridine orange
      [AO]) are used to stain DNA to determine if nuclei are apoptotic. However, there
      are numerous visual methods for counting these stained DNA that may lead to
      inaccuracies Measuring apoptosis by the visual counting method may be imprecise
      because of the variability of individuals' perception of color. Therefore, the
      authors compared a visual method of counting chromatin for apoptosis with a
      method relying on a computer program. They began counting chromatin using the
      visual method, in which individuals identify the stained DNA using their own
      visual perception. For comparison, they used a software-based counting method
      (analySIS software) to determine the color (hue) of the stained DNA. Using the
      numeric hue values from the software eliminates the variations in human color
      perception. Intra and interrater reliability of the visual and computer-assisted
      counting methods were evaluated with Spearman's. The authors found statistical
      significance in the intrarater reliability (r = 1.0, P = 0.0001 for all chromatin
      categories) and interrater reliability (r = 0.975, P = 0.005 for both readings)
      when using the software program. No statistical significance was found for the
      visual counting method, indicating inaccuracy between and within raters. Thus,
      the computer-assisted counting method of identifying the damaged DNA is more
      accurate and precise than the individual's visual perception of color. Based on
      these data, apoptosis measurements using color staining with EB and AO should be
      determined using hue values generated by a computer program and not by a
      researcher's visual assessment.

PMID- 15583359
TI  - Oxidative changes in cerebral spinal fluid phosphatidylcholine during treatment
      for acute lymphoblastic leukemia.
AB  - Central nervous system (CNS) treatment contributes to improved long-term disease
      free survival from childhood acute lymphoblastic leukemia (ALL) by significantly
      decreasing the rate of disease relapse. Methotrexate (MTX), a drug commonly used
      for CNS treatment, has been associated with cognitive and academic problems,
      white-matter changes, perfusion defects, and brain atrophy. This study
      investigated oxidative stress as a possible mechanism of chemotherapy induced CNS
      injury. Unoxidized and oxidized components of phosphatidylcholine (PC), the most
      prevalent phospholipid in CNS cellular membranes, were measured in cerebral
      spinal fluid (CSF) samples obtained from 21 children diagnosed with low (n = 7),
      standard (n= 7), or high (n= 7) risk ALL. Children with high-risk ALL received
      the most MTX, especially during the most intensive phase of treatment
      (consolidation). Phospholipids were extracted from CSF samples obtained at
      diagnosis and during the induction, consolidation, and continuation treatment
      phases. Unoxidized and oxidized PC were measured by normal phase high-performance
      liquid chromatography at 2 ultraviolet wavelengths (206 and 234 nm,
      respectively). Data were analyzed by 2-way repeated-measures analysis of
      variance. Results support the hypotheses that the highest levels of oxidized PC
      would be observed during the most intensive phase of ALL therapy and in the high
      risk ALL group. Findings provide preliminary evidence for chemotherapy-induced
      oxidative stress in CNS membrane phospholipids.

PMID- 15583360
TI  - Neural-immune interactions: implications for pain management in patients with low
      back pain and sciatica.
AB  - Bidirectional communication between the immune system and the brain and the
      implications of this communication are emerging concepts in pain research.
      Although representing a small portion of the disc degeneration syndromes, lumbar
      herniated discs can cause significant symptoms that may persist even after
      surgical interventions. Evolving evidence demonstrates that proinflammatory
      cytokines are a key mediator in the process of disc degeneration as well as in
      the pain experienced by those afflicted with lumbar herniated discs. Activated
      immune cells release proinflammatory cytokines, which signal the brain through
      humoral and neural routes. The brain responds by altering neural activity and
      promoting further production of proinflammatory cytokines within the brain and
      spinal cord. Increased local cytokine production by disc tissue irritates spinal
      nerve roots, resulting in pain and functional changes in neural activity. This
      review of the current literature explores the importance of cytokine production
      within the context of lumbar disc degeneration and lumbar spine pain.
      Furthermore, the significance of the neural-immune interaction will be examined
      as it relates to pain management and to patient treatment.

PMID- 15583361
TI  - Promoting health in type 2 diabetes: nurse-physician collaboration in primary
      care.
AB  - The purpose of this study is to examine effects of a nurse-physician
      collaborative approach to care of patients with type 2 diabetes and to determine
      possible effect sizes for use in computing sample sizes for a larger study. Forty
      patients from a family practice clinic with type 2 diabetes were randomly
      assigned to control or experimental groups. The control group received standard
      care, whereas the experimental group received standard care plus home visits from
      a nurse, as well as consultation with an exercise specialist and/or nutritionist.
      Follow-up continued for 3 months. Clinical end points included standard measures
      of diabetes activity as well as quality-of-life indicators. Focus group
      interviews were used to explore patients' responses to the program. Although
      findings were not statistically significant, a trend toward small to moderate
      positive effect sizes was found in glycosylated hemoglobin and blood pressure.
      Quality of life measures also showed a trend toward small to moderate, but
      nonsignificant, improvements in physical functioning, bodily pain, vitality,
      social and global functioning, energy, impact of diabetes, and health distress.
      Focus group interviews indicated a very positive response from patients, who
      expressed feelings of empowerment. In this study, patients treated with nurse
      physician collaboration demonstrated small, but nonsignificant, improvements in
      blood chemistry after only 3 months. Physical and social functioning, energy, and
      bodily pain also showed a small improvement. Changes in awareness of effects of
      diabetes on health and an expressed sense of self-efficacy suggest that effects
      could be sustainable over the longer term.

PMID- 15583362
TI  - Exploration of the contribution of biobehavioral variables to the energy
      expenditure of preterm infants.
AB  - Variation in energy expended by preterm infants may be due to infant maturity and
      history of resolved acute lung disease (respiratory distress syndrome [RDS]) as
      well as growth, caloric intake, and activity. Indirect calorimetry was used in
      this exploratory, short-term longitudinal study to estimate energy expenditure
      (EE) from measures of inspired and expired O2 and CO2. The sample included 35
      assessments for 10 preterm infants (5 with and 5 without RDS history). Lung
      disease history (resolved RDS, no RDS diagnosis), weight gain (g/d) from the day
      on which birth weight had been regained to the study day, mean activity level,
      the number of the assessment (1-6), and the interaction of lung disease history
      and time were included in a linear mixed model for repeated measures. Time was an
      index of postconceptional and postnatal age; all 3 were highly correlated.
      Because of high correlation with weight gain, caloric intake was not included in
      the analytic model. Lung disease history, mean activity level, and time were
      significant contributors to EE. A more precise measure of medical status than
      absence or presence of lung disease history, evenly spaced repetitions of EE
      assessment, and exploration of contexts in which the infants exhibit a higher
      activity level are needed in a replication study with a larger sample.

PMID- 15583363
TI  - A review of the role of proinflammatory cytokines in labor and noninfectious
      preterm labor.
AB  - The prevention of preterm labor has the potential to reduce newborn morbidity and
      mortality by decreasing the incidence of preterm birth. Half of all preterm
      births occur in women with no known clinical risk factors. Labor onset and
      progress is multifactorial, and we are just beginning to understand the role of
      cytokines in uterine activity. The purpose of this article is to review the role
      of cytokines in labor and preterm labor not associated with infection and to
      provide implications for research and practice.

PMID- 15583364
TI  - Trends in the sensitivity, positive predictive value, false-positive rate, and
      comparability ratio of hospital discharge diagnosis codes for acute myocardial
      infarction in four US communities, 1987-2000.
AB  - Variations in the validity of hospital discharge diagnoses can complicate the
      assessment of trends in incidence of acute myocardial infarction (AMI). To
      clarify trends in the validity of discharge codes, the authors compared event
      classification based on published Atherosclerosis Risk in Communities (ARIC)
      Study criteria with the presence or absence of an International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge
      code for AMI (code 410). Between 1987 and 2000, 154,836 coronary heart disease
      events involving hospitalization in the four ARIC communities had ICD-9-CM codes
      screened for AMI. The sensitivity of ICD-9-CM code 410 for classifying AMI in men
      (sensitivity = 0.65, 95% confidence interval (CI): 0.63, 0.66) was statistically
      significantly greater than that found for women (sensitivity = 0.60, 95% CI:
      0.58, 0.62) and was greater in Whites (sensitivity = 0.67, 95% CI: 0.65, 0.68)
      than in Blacks (sensitivity = 0.50, 95% CI: 0.47, 0.53). The ethnic difference
      was related to a greater frequency of hypertensive heart disease and congestive
      heart failure codes encompassing AMI among Blacks as compared with Whites. The
      authors found that although the validity of ICD-9-CM code 410 to identify AMI was
      generally stable from 1987 through 2000, differences between Blacks and Whites
      and across geographic locations support investment in validation efforts in
      ongoing surveillance studies.

PMID- 15583365
TI  - Invited commentary: Will heart attacks be "gone with the century"?

PMID- 15583367
TI  - Comparison of self-report, hospital discharge codes, and adjudication of
      cardiovascular events in the Women's Health Initiative.
AB  - Limited information is available from large clinical investigations about the
      agreement among sources of diagnoses for endpoints. The authors used data from
      the Women's Health Initiative clinical trials and observational study from
      January 1994 to November 2000 to evaluate the agreement among self-report,
      hospital discharge codes, and two different levels of physician review of medical
      records for cardiovascular endpoints. For myocardial infarction, stroke,
      pulmonary embolism, and venous thrombosis, the agreement of hospital discharge
      codes or self-report with review by study physicians at clinical centers was
      substantial (kappa = 0.64-0.84). For coronary revascularization, agreement among
      these sources of information was substantial to almost perfect (kappa = 0.79
      0.92), but for angina, congestive heart failure, and peripheral vascular disease,
      concordance was only fair to moderate (kappa = 0.37-0.56), indicating that these
      endpoints remain difficult to classify reliably. Agreement between physician
      adjudicators at clinical centers and central physician adjudicators was
      substantial to almost perfect (kappa = 0.67-0.94). The findings also suggest
      that, for the endpoint of myocardial infarction, physician review of events with
      hospital discharge codes for angina and congestive heart failure is an important
      source of validated events, and for stroke, review of all events with
      cerebrovascular codes is important.

PMID- 15583368
TI  - Relation of height, body mass, energy intake, and physical activity to risk of
      renal cell carcinoma: results from the Netherlands Cohort Study.
AB  - Data from the Netherlands Cohort Study on Diet and Cancer were used to
      investigate the association between anthropometry, energy intake, and physical
      activity and risk of renal cell carcinoma (RCC). The Netherlands Cohort Study on
      Diet and Cancer consists of 120,852 men and women aged 55-69 years who completed
      a self-administered questionnaire at baseline (1986). A case-cohort approach was
      used. After 9.3 years of follow-up, 275 microscopically confirmed incident cases
      were available for analysis. Incidence rate ratios for RCC were estimated using
      Cox proportional hazards models. Height was associated with RCC risk only in
      women (per 5-cm increment, rate ratio (RR) = 1.23, 95% confidence interval (CI):
      1.03, 1.46). Body mass index (weight (kg)/height (m)(2)) was associated with
      increased risk of RCC (per 1-kg/m(2 )increment, RR = 1.07, 95% CI: 1.02, 1.12)
      for men and women, as was gain in body mass index from age 20 years to baseline
      (per 1-kg/m(2 )increment, RR = 1.06, 95% CI: 1.01, 1.10). Energy intake was not
      related to RCC risk, while a possible protective effect was observed for physical
      activity in men. These results suggest that body mass index and gain in body mass
      index since age 20 are associated with increased risk of RCC.

PMID- 15583369
TI  - Relation of height and body mass index to renal cell carcinoma in two million
      Norwegian men and women.
AB  - A positive association between body mass index (BMI) and renal cell carcinoma
      (RCC) has been observed. The association between height and RCC has been less
      clear. The authors explored these relations in a very 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, 6,453 cases of RCC were registered in
      the national cancer database. Measurements were also performed in 227,000
      adolescents aged 14-19 years, and 154 cases of RCC were registered. Relative
      risks for RCC were estimated using Cox proportional hazards regression. The risk
      of RCC increased with increasing BMI among both adults and adolescents. Among
      adults, the relative risk associated with a one-unit increase in BMI was 1.05
      (95% confidence interval (CI): 1.04, 1.06) in both sexes. The relative risk
      associated with a 10-cm increase in height was 1.19 (95% CI: 1.13, 1.26) in men
      and 1.17 (95% CI: 1.09, 1.26) in women. In a subgroup analysis, the relation
      between BMI and RCC was most pronounced in men and women who were never smokers,
      and the relation between height and RCC was confined to ever smokers. The authors
      conclude that elevated BMIs are associated with RCC risk in both males and
      females across a wide age range.

PMID- 15583370
TI  - Serum polychlorinated biphenyls, cytochrome P-450 1A1 polymorphisms, and risk of
      breast cancer in Connecticut women.
AB  - Recent epidemiologic studies have suggested that genetic polymorphisms in the
      cytochrome P-450 1A1 gene (CYP1A1) may affect the relation between environmental
      exposure to polychlorinated biphenyls (PCBs) and breast cancer risk. The authors
      report results from a case-control study evaluating the potential effect of gene
      environment interaction between CYP1A1 and serum PCB levels on breast cancer risk
      among Caucasian women in Connecticut. The study included 374 case women with
      histologically confirmed breast cancer and 406 noncancerous controls with
      information on both serum PCB level and CYP1A1 genotype (1999-2002). Compared
      with women who had the homozygous wild-type CYP1A1 m2 genotype, significantly
      increased risks of breast cancer were found for women with the CYP1A1 m2 variant
      genotype (odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.1, 3.9),
      especially postmenopausal women (OR = 2.4, 95% CI: 1.1, 5.0). Risks associated
      with the CYP1A1 m2 variant genotype were highest for all women (OR = 3.6, 95% CI:
      1.5, 8.2) and postmenopausal women (OR = 4.3, 95% CI: 1.6, 12.0) with higher
      serum PCB levels (611-2,600 ng/g). The CYP1A1 m1 and m4 genotypes were not
      associated with breast cancer risk independently or in combination with PCB
      exposure. In summary, the CYP1A1 m2 genetic polymorphism was associated with
      increased risk of female breast cancer and may modify the relation between PCB
      exposure and breast cancer risk.

PMID- 15583371
TI  - Cumulative lead exposure and prospective change in cognition among elderly men:
      the VA Normative Aging Study.
AB  - Lead exposure has been found to affect cognitive function in several different
      populations. Whether chronic low-level environmental exposure to lead results in
      cognitive decline among adults has not been examined. The authors assessed the
      relation between biomarkers of lead exposure and change in Mini-Mental State
      Examination (MMSE) scores in the Normative Aging Study, a cohort of elderly US
      men. Bone lead was measured with K-shell x-ray fluorescence. A total of 466 men
      aged 67.4 (standard deviation, 6.6) years took the MMSE on two occasions that
      were an average of 3.5 (standard deviation, 1.1) years apart during the period
      1993-2001 and had bone lead concentrations measured during the period 1991-2002.
      A one-interquartile range (20 microg/g of bone mineral) higher patella bone lead
      concentration was associated with a change in MMSE score of -0.24 (95% confidence
      interval: -0.44, -0.05) after adjustment for age, education, smoking, alcohol
      intake, and time between MMSE tests. This effect is approximately equivalent to
      that of aging 5 years in relation to the baseline MMSE score in study data. The
      association with tibia lead was weaker and that with blood lead was absent. The
      data suggest that higher patella bone lead levels, a marker of mobilizable
      accumulated lead burden, are associated with a steeper decline over time in
      performance on the MMSE test among nonoccupationally exposed elderly men.

PMID- 15583372
TI  - Pesticide use and menstrual cycle characteristics among premenopausal women in
      the Agricultural Health Study.
AB  - Menstrual cycle characteristics may have implications for women's fecundability
      and risk of hormonally related diseases. Certain pesticides disrupt the estrous
      cycle in animals. The authors investigated the cross-sectional association
      between pesticide use and menstrual function among 3,103 women living on farms in
      Iowa and North Carolina. Women were aged 21-40 years, premenopausal, not pregnant
      or breastfeeding, and not taking oral contraceptives. At study enrollment (1993
      1997), women completed two self-administered questionnaires on pesticide use and
      reproductive health. Exposures of interest were lifetime use of any pesticide and
      hormonally active pesticides. Menstrual cycle characteristics of interest
      included cycle length, missed periods, and intermenstrual bleeding. The authors
      used generalized estimating equations to assess the association between pesticide
      use and menstrual cycle characteristics, controlling for age, body mass index,
      and current smoking status. Women who used pesticides experienced longer
      menstrual cycles and increased odds of missed periods (odds ratio = 1.5, 95%
      confidence interval: 1.2, 1.9) compared with women who never used pesticides.
      Women who used probable hormonally active pesticides had a 60-100% increased odds
      of experiencing long cycles, missed periods, and intermenstrual bleeding compared
      with women who had never used pesticides. Associations remained after control for
      occupational physical activity.

PMID- 15583373
TI  - Glucose tolerance and risk of gestational diabetes mellitus in nulliparous women
      who smoke during pregnancy.
AB  - Gestational diabetes mellitus has been associated with adverse maternal and
      infant outcomes, including preeclampsia and fetal macrosomia. Although cigarette
      smoking has been associated with increased insulin resistance, its effect on
      gestational diabetes mellitus risk is uncertain. The authors evaluated the
      effects of smoking on glucose tolerance in a cohort of pregnant women who
      participated in the Calcium for Preeclampsia Prevention trial, a randomized study
      of nulliparous women conducted in five US medical centers from 1992 to 1995.
      Results of screening and diagnostic testing for gestational diabetes mellitus
      were analyzed. For 3,774 of the 4,589 women enrolled, plasma glucose
      concentration 1 hour after a 50-g oral glucose challenge and complete information
      on pregnancy outcome were available; for 3,602 of the women, gestational diabetes
      mellitus status was known. Adjusted mean 1-hour plasma glucose concentration
      (mg/dl) was elevated in women who smoked at study enrollment (112.6, 95%
      confidence interval: 110.0, 115.3) compared with women who had never smoked
      (108.3, 95% confidence interval: 106.7, 109.8; p < 0.01). Women who smoked were
      at increased risk of gestational diabetes mellitus when criteria proposed by the
      National Diabetes Data Group were used (adjusted odds ratio = 1.9, 95% confidence
      interval: 1.0, 3.6). These findings support an association between smoking and
      gestational diabetes mellitus.

PMID- 15583374
TI  - Advanced paternal age and risk of fetal death: a cohort study.
AB  - A possible detrimental paternal age effect on offspring health due to mutations
      of paternal origin should be reflected in an association between paternal age and
      fetal loss. The authors used data from a prospective study of 23,821 pregnant
      women recruited consecutively to the Danish National Birth Cohort from 1997 to
      1999 to assess the association between paternal age and fetal death. Fathers of
      the pregnancies were identified by record linkage to population registers. The
      paternal age-related risks of fetal death and its components, early and late
      fetal loss, were estimated using survival analysis. Pregnancies fathered by a man
      aged 50 or more years (n = 124) had almost twice the risk of ending in a fetal
      loss compared with pregnancies with younger fathers (hazard ratio = 1.88, 95%
      confidence interval: 0.93, 3.82), after adjustment for maternal age, reproductive
      history, and maternal lifestyle during pregnancy. Various approaches to
      adjustment for potential residual confounding of the relation by maternal age did
      not affect the relative risk estimates. The paternal age-related risk of late
      fetal death was higher than the risk of early fetal death and started to increase
      from the age of 45 years. It should, however, be interpreted cautiously because
      of the restricted number of fetal deaths.

PMID- 15583375
TI  - Fruit, vegetable, and antioxidant intake and all-cause, cancer, and
      cardiovascular disease mortality in a community-dwelling population in Washington
      County, Maryland.
AB  - Higher intake of fruits, vegetables, and antioxidants may help protect against
      oxidative damage, thus lowering cancer and cardiovascular disease risk. This
      Washington County, Maryland, prospective study examined the association of fruit,
      vegetable, and antioxidant intake with all-cause, cancer, and cardiovascular
      disease death. CLUE participants who donated a blood sample in 1974 and 1989 and
      completed a food frequency questionnaire in 1989 (N = 6,151) were included in the
      analysis. Participants were followed to date of death or January 1, 2002.
      Compared with those in the bottom fifth, participants in the highest fifth of
      fruit and vegetable intake had a lower risk of all-cause (cases = 910; hazard
      ratio (HR) = 0.63, 95% confidence interval (CI): 0.51, 0.78; p-trend = 0.0004),
      cancer (cases = 307; HR = 0.65, 95% CI: 0.45, 0.93; p-trend = 0.08), and
      cardiovascular disease (cases = 225; HR = 0.76, 95% CI: 0.54, 1.06; p-trend =
      0.15) mortality. Higher intake of cruciferous vegetables was associated with
      lower risk of all-cause mortality (HR = 0.74, 95% CI: 0.60, 0.91; p-trend =
      0.04). No statistically significant associations were observed between dietary
      vitamin C, vitamin E, and beta-carotene intake and mortality. Overall, greater
      intake of fruits and vegetables was associated with lower risk of all-cause,
      cancer, and cardiovascular disease death. These findings support the general
      health recommendation to consume multiple servings of fruits and vegetables (5
      9/day).

PMID- 15583376
TI  - What happens to your manuscript: characteristics of papers published in volume
      160.

PMID- 15583377
TI  - Structure of a novel ribosome-inactivating protein from a hemi-parasitic plant
      inhabiting the northwestern Himalayas.
AB  - This is the first report of the structural studies of a novel ribosome
      inactivating protein (RIP) obtained from the Himalayan mistletoe (Viscum album)
      (HmRip). HmRip is a type II heterodimeric protein consisting of a toxic enzyme (A
      chain) with an active site for ribosome inactivation and a lectin subunit (B
      chain) with well defined sugar-binding sites. The crystal structure of HmRip has
      been determined at 3.8 A resolution and refined to a crystallographic R factor of
      0.228 (R(free) = 0.271). A comparison of this structure with other type II RIPs
      reveals the presence of distinct structural features in the active site of the A
      chain and in the 2gamma sugar-binding site of the B-chain. The conformation of
      the side chain of Tyr110, which is a conserved active-site residue in the A
      subunit, is strikingly different from those observed in other mistletoe RIPs,
      indicating its unique substrate-binding preference. The deletion of two important
      residues from the kink region after Ala231 in the 2gamma subdomain of the B-chain
      results in a significantly different conformation of the sugar-binding pocket. A
      ribosome-recognition site has also been identified in HmRip. The site is a
      shallow cavity, with the conserved residues Arg51, Asp70, Thr72 and Asn73
      involved in the binding. The conformations of the antigenic epitopes of residues
      1-20, 85-103 and 206-223 differ from those observed in other type II RIPs,
      resulting in the distinct antigenicity and pharmacological properties of HmRip.

PMID- 15583378
TI  - Structure of photoactive yellow protein (PYP) E46Q mutant at 1.2 A resolution
      suggests how Glu46 controls the spectroscopic and kinetic characteristics of PYP.
AB  - Photoactive yellow protein from Ectothiorhodospira halophila is a photoreceptor
      protein involved in the negative phototaxis of this bacterium. Its chromophore (p
      coumaric acid) is deprotonated in the ground state, which is stabilized by a
      hydrogen-bond network between Tyr42, Glu46 and Thr50. Glu46 is a key residue as
      it has been suggested that the proton at Glu46 is transferred to the chromophore
      during its photoconversion from the dark state to the signalling state. The
      structure of E46Q mutant protein was determined at 1.2 A resolution, revealing
      that the phenolic O atom of p-coumaric acid is hydrogen bonded to NH(2) of Gln46
      in E46Q with a longer distance (2.86 +/- 0.02 A) than its distance (2.51 A) to
      Glu46 OH in the wild type. This and the decreased thermal stability of E46Q
      relative to the wild type show that this hydrogen bond is weakened in the E46Q
      mutant compared with the corresponding bond in the wild type. Several
      characteristic features of E46Q such as an alkali shift in the pK(a) and the
      rapid photocycle can be explained by this weakened hydrogen bond. Furthermore,
      the red shift in the absorption maximum in E46Q can be explained by the
      delocalization of the electron on the phenolic oxygen of p-coumaric acid owing to
      the weakening of this hydrogen bond.

PMID- 15583379
TI  - Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding
      of shikimic acid.
AB  - Tuberculosis made a resurgence in the mid-1980s and now kills approximately 3
      million people a year. The re-emergence of tuberculosis as a public health
      threat, the high susceptibility of HIV-infected persons and the proliferation of
      multi-drug-resistant strains have created a need to develop new drugs. Shikimate
      kinase and other enzymes in the shikimate pathway are attractive targets for
      development of non-toxic antimicrobial agents, herbicides and anti-parasitic
      drugs, because the pathway is essential in these species whereas it is absent
      from mammals. The crystal structure of shikimate kinase from Mycobacterium
      tuberculosis (MtSK) complexed with MgADP and shikimic acid (shikimate) has been
      determined at 2.3 A resolution, clearly revealing the amino-acid residues
      involved in shikimate binding. This is the first three-dimensional structure of
      shikimate kinase complexed with shikimate. In MtSK, the Glu61 residue that is
      strictly conserved in shikimate kinases forms a hydrogen bond and salt bridge
      with Arg58 and assists in positioning the guanidinium group of Arg58 for
      shikimate binding. The carboxyl group of shikimate interacts with Arg58, Gly81
      and Arg136 and the hydroxyl groups interact with Asp34 and Gly80. The crystal
      structure of MtSK-MgADP-shikimate will provide crucial information for the
      elucidation of the mechanism of the shikimate kinase-catalyzed reaction and for
      the development of a new generation of drugs against tuberculosis.

PMID- 15583380
TI  - Structural basis for discrimination between oxyanion substrates or inhibitors in
      aspartate-beta-semialdehyde dehydrogenase.
AB  - The reversible dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta
      semialdehyde (ASA) in the aspartate biosynthetic pathway is catalyzed by
      aspartate-beta-semialdehyde dehydrogenase (ASADH). The phosphate that is present
      to activate the aspartate carboxyl group is held in a separate and distinct
      binding site once removed and prior to its release from the enzyme. This site had
      been shown to be selective for tetrahedral oxyanions, with several competitive
      inhibitors and alternative substrates previously identified for the reverse
      reaction. Structural studies have now shown that the most potent oxyanion
      inhibitor (periodate) and a good alternative substrate (arsenate) each occupy the
      same catalytic phosphate-binding site. However, a rotation of a threonine side
      chain (Thr137) in the periodate complex disrupts an important hydrogen-bonding
      interaction with an active-site glutamate (Glu243) that participates in substrate
      orientation. This subtle change appears to be the difference between a substrate
      and an inhibitor of this enzyme.

PMID- 15583381
TI  - Purification, crystallization and preliminary X-ray analysis of the N-terminal
      domain of NO38, a nucleolar protein from Xenopus laevis.
AB  - NO38 is a multidomain protein that belongs to the nucleoplasmin (Np) family.
      Previous studies have suggested that acidic chaperones such as Np may function as
      histone-storage platforms. Here, the purification and crystallization of the N
      terminal domain of NO38 in two crystal forms is reported. The C2 crystal form
      diffracts to 1.9 A and contains two pentamers in the asymmetric unit, while the
      P1 crystals diffract to 1.7 A and contain a non-crystallographic decamer with 522
      symmetry. By analogy with Np, the NO38 decamer may represent the active form of
      this chaperone.

PMID- 15583382
TI  - Crystallization and preliminary X-ray diffraction analysis of ferredoxin-NADP(H)
      reductase from Rhodobacter capsulatus.
AB  - Ferredoxin-NADP(H) reductase (272 amino acids) from Rhodobacter capsulatus (FPR)
      has recently been postulated to be involved in the antioxidant response and to
      facilitate the provision of reduced flavodoxin for the reduction of nitrogenase.
      Crystallization trials of recombinant FPR were carried out at 291 K by the
      hanging-drop vapour-diffusion method. Orthorhombic crystals (unit-cell parameters
      a = 69.3, b = 93.6, c = 103.5 A) were obtained. However, their diffraction
      pattern was not satisfactory and an extensive detergent screening was carried out
      over the initial crystallization conditions. The introduction of n-heptyl-beta-D
      thioglucoside produced new trigonal crystals (space group P3(1)21; unit-cell
      parameters a = b = 120.5, c = 51.1 A) that diffracted to 1.8 A resolution at
      beamline BM16 at the ESRF. Preliminary structural analysis indicated that
      detergent molecules could increase the quality of diffraction of FPR crystals by
      stabilizing the disordered regions of the protein and by increasing the number of
      contacts in the crystal packing.

PMID- 15583383
TI  - Crystallization and preliminary X-ray analysis of the coiled-coil domain of
      dystrophia myotonica kinase.
AB  - The coiled-coil domain of dystrophia myotonica protein kinase (DMPK) has been
      cloned, overexpressed, purified and crystallized. Two crystal forms have been
      obtained that belong to space groups P3 and P2(1)2(1)2(1) and diffract to 2.4 and
      1.6 A resolution, respectively. Experimental phases were obtained by MAD from an
      SeMet derivative. The location of selenium sites used molecular-replacement
      phases obtained from search models lacking sequence similarity with the coiled
      coil under study. Both crystal forms contain three polypeptide chains in the
      asymmetric unit.

PMID- 15583384
TI  - Crystallization and preliminary crystallographic analysis of the 2'-aminobiphenyl
      2,3-diol 1,2-dioxygenase from the carbazole-degrader Pseudomonas resinovorans
      strain CA10.
AB  - CarBaBb, the class III extradiol dioxygenase involved in carbazole degradation by
      Pseudomonas resinovorans CA10, was crystallized at 278 K by the hanging-drop
      vapour-diffusion method using PEG MME 550 as a precipitant. The crystals had a
      transparent thin square-pillar shape and belonged to space group P2(1)2(1)2, with
      unit-cell parameters a = 122.8, b = 144.6, c = 49.2 A, alpha = beta = gamma = 90
      degrees . The crystals diffracted to a maximum resolution of 1.9 A and gave a
      data set with an overall R(merge) of 5.7% and a completeness of 98.6%. The V(M)
      value was 2.52 A(3) Da(-1), which indicated a solvent content of 51.2%.

PMID- 15583385
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      hydroxycinnamoyl-coenzyme A hydratase-lyase (HCHL), a crotonase homologue active
      in phenylpropanoid metabolism.
AB  - 4-Hydroxycinnamoyl-coenzyme A hydratase-lyase (HCHL), also called feruloyl-CoA
      hydratase-lyase (FCHL), from Pseudomonas fluorescens strain AN103 is an enzyme of
      the crotonase superfamily that catalyses the one-step conversion of the CoA
      thioesters of 4-coumaric acid, caffeic acid and ferulic acid to the aromatic
      aldehydes 4-hydroxybenzaldehyde, protocatechuic aldehyde and vanillin,
      respectively. The reaction occurs via a hydration followed by a carbon-carbon
      bond-cleavage reaction. HCHL has been crystallized by the hanging-drop method of
      vapour diffusion using polyethylene glycol 20 000 Da as the precipitant. The
      crystals belong to the orthorhombic system, with proposed space group P2(1)2(1)2
      and unit-cell parameters a = 154.2, b = 167.5, c = 130.8 A. The V(M) suggests
      that the asymmetric unit contains four trimers. Single-wavelength data collection
      has been undertaken and structure determination is under way by molecular
      replacement using data collected to 1.8 A resolution. Determination of the
      structure of HCHL will provide insight into the catalytic mechanism of an unusual
      enzymatic reaction with relevance to the applications of the enzyme in metabolic
      engineering.

PMID- 15583386
TI  - Crystallization and initial crystallographic analysis of the Kelch domain from
      human Keap1.
AB  - The human Keap1 protein is a substrate adaptor for an E3 ubiquitin ligase complex
      that specifically targets the transcription factor Nrf2 for degradation. Keap1
      functions as a sensor of oxidative stress, such that the inhibition of Keap1
      dependent degradation of Nrf2 activates a genetic program that protects cells
      from reactive chemicals and maintains cellular redox homeostasis. Keap1 interacts
      with Nrf2 through its C-terminal Kelch-repeat domain. Kelch-repeat domains are
      found in a large number of proteins and are predicted to assemble into a beta
      propeller structure. Only a single Kelch-repeat domain, that from the fungal
      enzyme galactose oxidase, has had its structure determined. Here, the
      crystallization of the Kelch domain of human Keap1 protein by hanging-drop vapor
      diffusion is reported in space group P6(5)22. Crystals diffract to 1.85 A
      resolution under cryocooling conditions. A selenomethionine-substituted version
      of the Kelch domain has also been purified and crystallizes isomorphously with
      the native protein. Structure determination by MAD phasing is under way. The role
      of Keap1 in oxidative stress and cytoprevention suggests that the Kelch domain
      will be an attractive target for therapeutic drug design.

PMID- 15583387
TI  - Crystallization and preliminary crystallographic studies of MOMP (major outer
      membrane protein) from Campylobacter jejuni.
AB  - Campylobacter jejuni is the leading bacterial cause of human enteritis linked to
      ingestion of contaminated food or water. MOMP, the major outer membrane protein
      from these Gram-negative bacteria, belongs to the porin family. In order to
      determine the three-dimensional structure of this protein and to elucidate the
      underlying molecular mechanisms, the MOMP from C. jejuni strain 85H has been
      purified and crystallized by vapour diffusion. Two crystal forms were
      characterized for this membrane protein. X-ray diffraction data were collected to
      a resolution of 3.1 A using a synchrotron-radiation source from the orthorhombic
      crystal form, which belonged to space group P2(1)2(1)2 with unit-cell parameters
      a = 170.1, b = 101.9, c = 104.9 A. With a trimer in the asymmetric unit, the
      solvent content is 64% (V(M) = 3.4 A Da(-1)). The other form exhibits trigonal
      symmetry (space group R3) with hexagonal unit-cell parameters a = b = 94.2, c =
      161.2 A, but diffracts X-rays poorly to about 4 A with significant anisotropy.

PMID- 15583388
TI  - Expression, crystallization and preliminary X-ray crystallographic studies of
      Klebsiella pneumoniae maltohexaose-producing alpha-amylase.
AB  - A recombinant form of Klebsiella pneumoniae maltohexaose-producing alpha-amylase
      has been overexpressed in Escherichia coli and purified to homogeneity. Crystals
      were obtained at 293 K by the microbatch technique using 80 mM sodium/potassium
      phosphate buffer pH 6.2 containing 8% polyethylene glycol 3000, 4% polyethylene
      glycol 3350 and 40 mM sodium thiocyanate. Crystals of the overexpressed
      recombinant enzyme diffracted to better than 2.5 A resolution at 95 K using a
      synchrotron-radiation source. The crystals belong to the primitive monoclinic
      space group P2(1), with unit-cell parameters a = 74.8, b = 107.6, c = 82.2 A,
      beta = 96.2 degrees. Assuming the presence of two molecules per asymmetric unit,
      the V(M) value for the crystal was 2.3 A(3) Da(-1), indicating a solvent content
      of 47%.

PMID- 15583389
TI  - Crystallization of parasporin-2, a Bacillus thuringiensis crystal protein with
      selective cytocidal activity against human cells.
AB  - Bacillus thuringiensis is a valuable source of protein toxins that are
      specifically effective against certain insects and worms but harmless to mammals.
      In contrast, a protein toxin obtained from B. thuringiensis strain A1547,
      designated parasporin-2, is not insecticidal but has a strong cytocidal activity
      against human cells with markedly divergent target specificity. The 37 kDa
      inactive protein is proteolytically activated to a 30 kDa active form. The active
      form of the recombinant protein toxin was crystallized in the presence of
      ethylene glycol and polyethylene glycol 8000 at neutral pH. The crystals belong
      to the hexagonal space group P6(1) or P6(5), with unit-cell parameters a = b =
      134.37, c = 121.24 A. Diffraction data from a native crystal were collected to
      2.75 A resolution using a synchrotron-radiation source.

PMID- 15583390
TI  - Expression, purification and preliminary crystallographic characterization of a
      novel segment from the neurofibromatosis type 1 protein.
AB  - Neurofibromin (MW 320 kDa) is the protein responsible for the pathogenesis of
      neurofibromatosis type 1 (NF1), one of the most common genetic diseases
      worldwide. The neurofibromin GAP-related domain (GRD, MW 38 kDa) possess a Ras
      specific GTPase-activating protein property, which is at present its only clear
      biochemical function. This article describes the study of the bacterial
      production and preliminary X-ray crystallographic analysis of a neurofibromin
      fragment located at the C-terminal end of the GRD, which contains a region
      reported to be homologous to the yeast Sec14p lipid exchange protein. Of the
      three crystal variants obtained, a tetragonal form diffracted to a resolution of
      at least 2.3 A.

PMID- 15583391
TI  - Crystallization and preliminary X-ray diffraction analysis of bacteriophage
      varphi12 packaging factor P7.
AB  - Bacteriophage varphi12 protein P7 is a structural component of the polymerase
      complex and ensures stable packaging of the genomic RNA. varphi12 P7 has been
      cloned, purified and crystallized. Crystals belong to space group P3(2)21, with
      unit-cell parameters a = 75.7, b = 75.7, c = 45.2 A, alpha = 90, beta = 90, gamma
      = 120 degrees , and diffract beyond 2.0 A. Multiple anomalous dispersion data
      have been collected from crystals of selenomethionylated P7. Mass spectroscopy
      showed proteolysis of the crystallized protein and a truncated form, P7DeltaC,
      gave crystals of similar morphology. Cross-linking experiments implicated the N
      terminal domain of P7 as being essential for dimerization.

PMID- 15583392
TI  - Preliminary crystallographic characterization of BSAP, an extracellular
      aminopeptidase from Bacillus subtilis.
AB  - The extracellular aminopeptidase from Bacillus subtilis (BSAP) has recently been
      cloned, overexpressed and purified from Escherichia coli. It is a monomer with a
      molecular weight of 46 425 Da, consisting of 425 amino-acid residues and a double
      zinc catalytic centre. The recombinant enzyme was found to be stable for 20 min
      at 353 K, to function optimally in the pH range 8-9 and to prefer basic and large
      hydrophobic N-terminal amino acids in peptide and protein substrates. As such,
      this enzyme can be used as a representative model for structural, functional and
      mechanistic studies of monomeric double-zinc aminopeptidases, many of which have
      been found to be involved in medically important biological activities. In this
      report, the crystallization and preliminary crystallographic characterization of
      wild-type BSAP are described. Two different crystal forms are reported, of which
      the hexagonal form H2 is the more suitable for structural study, with average
      unit-cell dimensions a = b = 226.5, c = 42.8 A. A full diffraction data set has
      been collected from such a crystal of the native enzyme (2.2 A resolution, 91.2%
      completeness, R(merge) = 7.1%). A multiwavelength anomalous diffraction (MAD)
      data set was collected on native (zinc-containing) BSAP at three wavelengths
      around the zinc absorption edge (peak data set at 2.5 A resolution, 98.8%
      completeness, R(merge) = 5.3%). These diffraction data were collected at 95-100 K
      using a synchrotron X-ray source and a CCD area detector. The data are currently
      being used to obtain crystallographic phasing and to determine the detailed three
      dimensional structure of the enzyme.

PMID- 15583393
TI  - Crystallization and preliminary crystallographic analysis of the heptad-repeat
      complex of SARS coronavirus spike protein.
AB  - The aetiological agent of an emergent outbreak of atypical pneumonia, severe
      acute respiratory syndrome (SARS), is a positive-stranded RNA virus (SARS-CoV)
      belonging to the Coronaviridae family with a genome that differs substantially
      from those of other known coronaviruses. Highly conserved heptad-repeat (HR1 and
      HR2) regions in class I viral fusion proteins, including spike protein from SARS
      coronavirus, interact with each other to form a six-helix bundle, which is called
      a fusion core. The crystal structure of the fusion core is expected to greatly
      facilitate drug design. Crystals of the fusion core of SARS-CoV spike protein
      have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern
      of the crystal extends to 2.8 A resolution at 100 K in-house. The crystals have
      unit-cell parameters a = 121.2, b = 66.3, c = 70.0 A, alpha = gamma = 90, beta =
      107.4 degrees and belong to space group C2. Assuming the presence of six
      molecules per asymmetric unit, the solvent content is estimated to be about 28%.

PMID- 15583394
TI  - Crystallization and preliminary X-ray diffraction analysis of the unliganded
      human growth hormone receptor.
AB  - The crystal structure of the extracellular domain of growth hormone receptor
      complexed to its ligand, growth hormone, has been known since 1992. However, no
      information exists for the unliganded form of the receptor. The human growth
      hormone receptor's extracellular ligand-binding domain, encompassing amino-acid
      residues 1-238, has been expressed in Escherichia coli, purified by anion ion
      exchange chromatography and crystallized in its unliganded state by the hanging
      drop vapour-diffusion method in 100 mM HEPES pH 7.0 containing 27.5%(w/v) PEG
      5000 monomethyl ether and 200 mM ammonium sulfate as the co-precipitants. The
      crystals belong to the othorhombic space group C222(1), have unit-cell parameters
      a = 99.7, b = 112.2, c = 93.2 A and diffract to 2.5 A resolution using
      synchrotron radiation. The crystal structure will shed light on the nature of any
      conformation changes that occur upon ligand binding and will provide information
      to develop potential low-molecular-weight agonists/antagonists to treat clinical
      diseases in which the growth hormone receptor is implicated.

PMID- 15583395
TI  - Crystallization and preliminary X-ray crystallographic studies of dissimilatory
      nitrite reductase isolated from Hyphomicrobium denitrificans A3151.
AB  - Dissimilatory nitrite reductase isolated from Hyphomicrobium denitrificans A3151
      (HdNIR) is a novel copper-containing nitrite reductase (CuNIR) composed of six
      identical subunits. One plastocyanin-like domain and one green CuNIR-like domain
      are connected to each other, suggesting that the HdNIR subunit structure
      resembles a complex of green CuNIR and pseudoazurin (or azurin). Recombinant
      HdNIR protein was crystallized using the hanging-drop vapour-diffusion method
      with PEG 4000 as the precipitant at pH 8.9. X-ray diffraction data were collected
      to 2.35 A resolution. The HdNIR crystal belonged to the tetragonal space group
      P4(1) (or P4(3)), with unit-cell parameters a = b = 221.9, c = 165.2 A, giving 12
      molecules (two hexamers) per asymmetric unit and a solvent content of 64%. A
      mutant form of HdNIR, C260A, which lacks the type I copper ion in the CuNIR-like
      domain, was prepared and crystallized under wild-type HdNIR conditions. The C260A
      mutant crystal belonged to the cubic space group P4(3)32 (or P4(1)32), with unit
      cell parameters a = b = c = 153.7 A, giving one molecule per asymmetric unit and
      a solvent content of 59%. X-ray diffraction data were collected to 3.5 A
      resolution. To solve the crystal structure of HdNIR, the multiwavelength
      anomalous dispersion (MAD) method and the molecular-replacement method are
      currently being used.

PMID- 15583396
TI  - Crystallization and preliminary crystallographic studies of human coactosin-like
      protein (CLP).
AB  - The human coactosin-like protein (CLP) belongs to the actin-depolymerizing factor
      (ADF) family of actin-binding proteins. CLP interacts with 5-lipoxygenase (5LO)
      and filamentous actin (F-actin) via different binding sites. The full-length CLP
      comprising of 142 amino acids has been overexpressed in Escherichia coli.
      Crystals of CLP were obtained using the hanging-drop vapour-diffusion technique
      with ammonium sulfate as precipitant at pH 8.5. Diffraction data to 1.9 A
      resolution were collected from a crystal belonging to space group P2(1), with
      unit-cell parameters a = 25.6, b = 55.2, c = 37.4 A, beta = 96.0 degrees. There
      is one molecule per asymmetric unit.

PMID- 15583397
TI  - Escherichia coli stress protein YciF: expression, crystallization and preliminary
      crystallographic analysis.
AB  - The Escherichia coli stress protein YciF was overexpressed and purified by three
      chromatographic steps. Crystals were obtained using ammonium sulfate as a
      precipitant. The YciF protein crystals diffracted beyond 2.25 A resolution using
      a rotating-anode X-ray source. The lattice type is rhombohedral, with unit-cell
      parameters a = b = 80.0, c = 131.03 A, alpha = beta = 90.0, gamma = 120.0
      degrees. The crystal belongs to space group R32.

PMID- 15583398
TI  - Crystallization and preliminary X-ray crystallographic analysis of a non-specific
      lipid-transfer protein with antipathogenic activity from Phaseolus mungo.
AB  - A 9 kDa non-specific lipid-transfer protein (nsLTP) from mung bean (Phaseolus
      mungo) seeds, displaying antifungal activity, antibacterial activity and lipid
      transfer activity, was crystallized at 297 K using ammonium sulfate as a
      precipitant by means of the hanging-drop vapour-diffusion method. Native X-ray
      diffraction data were collected to a resolution of 2.4 A. The crystals are
      rhombohedral, belonging to space group P2(1)2(1)2(1), with unit-cell parameters a
      = 38.671, b = 51.785, c = 55.925 A. Assuming the presence of one molecule in the
      crystallographic asymmetric unit results in a Matthews coefficient (V(M)) of
      approximately 3.0 A(3) Da(-1), corresponding to a solvent content of about 58%.

PMID- 15583399
TI  - Crystallization, X-ray diffraction and oligomeric characterization of arginine
      decarboxylase from Yersinia pestis, a key polyamine biosynthetic enzyme.
AB  - Arginine decarboxylase (ADC) is a 70 kDa pyridoxal-5'-phosphate (PLP) dependent
      enzyme that controls an alternative step in the biosynthesis of polyamines in
      some bacteria and plants. Crystals of ADC were flash-cooled and diffracted to 3.0
      A resolution using a synchrotron-radiation source. Crystals of ADC are
      monoclinic, with four monomers in the asymmetric unit. Light-scattering data
      reveals that the enzyme forms dimers in solution. The rotation function suggests
      the presence of two dimers in the asymmetric unit. Heavy-atom searches have
      identified PCMBS as forming a mercury derivative.

PMID- 15583400
TI  - Crystallography of the integral membrane protein EmrE from Escherichia coli.
AB  - Crystals of the EmrE membrane-protein imposed several technical challenges for X
      ray crystallography, including high mosaicity, poor diffraction and a relatively
      large number of heavy atoms. Consequently, the heavy-atom substructure solution
      was difficult to obtain. By removing the histidine tag for protein purification,
      the mosaicity and the diffraction quality were greatly improved. The direct
      methods Shake-and-Bake program SnB was successful in locating the heavy-atom
      sites from a mutant of EmrE which lacks a cysteine and therefore has a reduction
      in the number of heavy-atom sites. The substructure solution was solved from data
      with anomalous difference at a resolution of 5.5 A and the structure was
      determined to 3.8 A.

PMID- 15583401
TI  - SAD at home: solving the structure of oxalate decarboxylase with the anomalous
      signal from manganese using X-ray data collected on a home source.
AB  - Oxalate decarboxylase (OxdC) from Bacillus subtilis is a hexamer containing two
      manganese ions per 43.6 kDa subunit. A single highly redundant data set collected
      at a medium resolution of 2 A on an in-house X-ray source was sufficient to solve
      the structure by the single-wavelength anomalous diffraction (SAD) method using
      the anomalous signal from the manganese ions. The experimentally phased electron
      density map was of high quality, enabling 96% of the amino-acid sequence to be
      automatically traced using ARP/wARP. Further analysis showed that only half of
      the original raw data were required for successful structure solution. Manganese
      currently occurs in approximately 2% of PDB entries. A brief survey suggests that
      several of these structures could also have been determined using manganese SAD.
      Moreover, the ability of manganese to substitute for other more commonly
      occurring divalent metal ions may indicate that the use of Mn SAD could have much
      wider application.

PMID- 15583402
TI  - [Sugar transport, metabolism, accumulation and their regulation in fruits].
AB  - Photosynthates transported into fruits are mainly in the form of sucrose in most
      fruit tree species; but sorbitol takes the place of sucrose in woody Rosaceae
      plants. The transport of sugars across the plasma membrane from apoplastic space
      into cells is mediated by sugar transporters. The fact that gene expression of
      sugar transporters is upregulated just before and during sugar accumulation
      suggests the participation of sugar transporters in sugar accumulation of fruit.
      The sucrose-metabolizing enzymes participate in four futile cycles that involve
      sugar transport between cytosol, vacuole, amyloplast and apoplast. The increase
      in SS (sucrose synthase) and SPS (sucrose phosphate synthase) activities and mRNA
      levels during maturation parallels the increase in sugar accumulation indicates
      that the sucrose-metabolizing enzymes have important roles on sugar accumulation
      in fruits. The prerequisite for rapid accumulation of sugar in fruit is
      restriction of hexose catabolism and promotion of its synthesis. In woody
      Rosaceae plants, the fact that sucrose metabolism is also quite active in fruit
      suggests that sorbitol and sucrose probably play similar roles in fruit
      development. Sugars as signal molecules regulate the expression of genes involved
      in sugar transport and metabolism. Sugar transport, metabolism and accumulation
      are also regulated by natural environmental factors and cultural practices. The
      increase in sugar content of tomato fruit in acid invertase gene antisense
      inhibited plants provides promising prospect of genetic engineering as a
      potential effective technique in regulation of sugar accumulation in fruits.
      Thus, the sugar content of fruit is determined by both intrinsic and extrinsic
      factors. The future research works will be focused on elucidating the mechanism
      of sugar signal and other intrinsic signals as well as extrinsic signals
      including nutrients, plant hormones and physical factors on sugar transport,
      metabolism and accumulation and the interrelationship among them.

PMID- 15583403
TI  - [Plant volatiles and their metabolic engineering].
AB  - Plant volatiles mainly include terpenoid, benzenoid/phenylpropanoid and fatty
      acid derivatives, and they play diverse roles in plant-plant and plant-insect
      communications. In recent years, great progress has been made in biochemical and
      molecular characterization of the formation and release of these volatiles, and
      this make it possible to dissect their biological functions. More than 30 kinds
      of genes related with biosynthesis of these volatiles have been cloned. The
      pathways leading to synthesis of these metabolites can be controlled by enzyme
      activity and the substrates available as well as gene architecture. Plant
      volatiles can serve as attractants for specific pollinators, important cellular
      regulators in developmental processes and protection against environmental
      stress, whereas those released after herbivory or pathogen attacks can induce the
      expression a set of defensive genes or attraction of predators of the herbivores.
      An attractive prospect in this area is to design scent spectrum of plant with
      genetic and molecular technology. Two alternative approaches are used to
      genetically engineer these plant volatiles. One is based on the introduction of
      foreign genes encoding enzymes with activities that are missing in target plant,
      while the other is focused on modulating the expression of native genes.

PMID- 15583404
TI  - [Changes in antioxidative system and cell ultrastructure in the fruit peels of
      apple during sunburn development].
AB  - Fruits from 6-year-old apple trees (Malus domestica Borkh cv. Fuji) were used as
      materials to test the changes of antioxidative system and cell ultrastructure of
      fruit peels during sunburn development. Fruit sunburn appeared in mid July, 2002.
      The process of apple fruit sunburn was divided into three phases (0 degrees :
      control): 1 degrees : bleaching, 2 degrees : brownness, and 3 degrees : necrosis.
      Fuji apple fruits in different sunburn state were picked. Phenolic compounds,
      membrane protective enzymes (SOD, POD, PPO, CAT), cell membrane lipid
      peroxidation and cell ultrastructure in fruit peel were studied. The result
      showed that the degree of cell membrane lipid peroxidation enhanced along with
      development of sunburn. The activity of membrane protective enzymes also
      increased remarkably. However, the cell structure kept its integrity, except some
      organelles which partly disassembled, and cytoplasm and vacuoles became enriched
      with electron-dense substances while fruit peels became pale. As peel became
      brown, chlorogenic acid, quercetin, rutin and myricetin accumulated, and cells of
      outer layers of the epidermis collapsed correspondingly, cell wall became
      thicker. It is suggested that changes in both cell ultrastructure and
      antioxidative system confirm that physiological state of fruit peels becomes
      disordered during sunburn development.

PMID- 15583405
TI  - [Phenotype analysis of ethylene response in tomato Epinastics mutant].
AB  - The characteristics in seedling development, vegetative growth and fruit ripening
      of Epinastics (Epi) mutant overproducing ethylene and its wild type VFN8 tomato
      (Lycopersicon esculentum Mill.) were systematically investigated. Epi
      overproduced ethylene during vegetative growth and fruit development. Incomplete
      triple response in etiolated seedling, strong petiole episnasty in adult plant,
      and accelerated abscission and fruit ripening displayed enhanced ethylene
      response, consistent with the known mode of ethylene response. Significant apical
      dominance and compact vegetative shape in Epi suggested an important role of
      ethylene in the regulation of apical dominance. The characteristics such as
      inhibited apical hook formation in etiolated seedling and delayed senescence of
      leaves and petals in Epi, which were not typical of symptoms induced by ethylene,
      suggest that different growth and developmental characteristics are possibly
      regulated through different signal transduction pathways.

PMID- 15583406
TI  - [Accumulation of coat protein of Turnip mosaic virus in host chloroplasts and its
      effect on PS II activity].
AB  - Intact chloroplasts were isolated from Chinese cabbage (Brassica chinensis L. cv.
      Suzhou) and mustard (B. juncea L. cv. Wenzhou) leaves inoculated with Turnip
      mosaic virus (TuMV). The proteins attached to the surface of chloroplasts were
      digested, then the total proteins of chloroplasts were extracted. By analysis of
      the SDS-PAGE pattern, one extra protein band with the same mobility and molecular
      weight as TuMV-coat protein was found in the chloroplasts of infected leaves.
      Results of Western blotting showed that this band was highly reactive to the
      antiserum against TuMV-CP. The detection of immunogold-particles also showed the
      presence of TuMV-CP in chloroplasts of both host plant species as compared with
      the healthy control plant. Electron microscopic photograph showed some virus
      particles and cylindrical inclusions in the cytoplasm of host plants. Some
      chloroplasts showed abnormalities, including inhibited lamellar development,
      swollen and rounded, membrane vesiculation and disintegration. On the tenth day
      after TuMV inoculation, F(v) /F(o), F(v)/ F(m), Phi(PS II) and q(P) values all
      became lower, but the q(N) values were higher, as compared with the healthy
      control plants. The results provided the evidence for the presence of TuMV-CP in
      the diseased chloroplasts. It suggests that the accumulation of TuMV-CP inside
      chloroplasts affect photosynthesis in virus-infected plants by inhibiting the PS
      II activity.

PMID- 15583407
TI  - [Changes in ultraweak luminescence, ATP and active oxygen contents during apricot
      florescence].
AB  - Badan Shuixing apricot (Amenia cavulgaris Lam.) was used to study the changes in
      UWL intensity and its relationship to ATP content, respiration rate and active
      oxygen production rate during florescence of apricot. The results indicated that
      the production rate of active oxygen was smooth before the peak season of
      blossom, the UWL intensity and ATP content were both rise and the respiration
      rate also showed the trend of rise mainly at the same time. After the peak season
      of blossom, the respiration rate and ATP content declined rapidly while the UWL
      intensity went down slowly, but the active oxygen production rate increased
      rapidly. The protein content increased at first and then decreased during the
      florescence of apricot. The change in MDA content was similar to the change in
      active oxygen production rate, which rose rapidly after the peak season of
      blossom. It was concluded that the UWL was closely related to the energy level
      symbolized by ATP content and was affected by active oxygen metabolism in the
      apricot flower. The ATP content was the main factor to lead to the rise of UWL
      before the full bloom stage while the action of active oxygen on UWL appeared
      just after the peak season of blossom.

PMID- 15583408
TI  - Tonoplast H+-ATPase activity in barley roots is regulated by ATP and
      pyrophosphate contents under NaCl stress.
AB  - The changes in ATP and PPi contents in roots under NaCl stress, and the effect of
      PPi on tonoplast H(+)-ATPase activity were studied with two barley cultivars
      differing in salt tolerance. The results showed that tonoplast H(+)-ATPase
      activity in salt-tolerant barley cultivar "Tanyin 2" roots increased obviously
      under NaCl 200 mmol/L (containing half-strength Hoagland solution) for 2 d, and
      decreased gradually. Tonoplast H(+)-PPase activity always decreased under NaCl
      stress. For salt-sensitive barley cultivar "Kepin 7", both tonoplast H(+)-ATPase
      and H(+)-PPase activities decreased during NaCl stress, as compared with
      control(grown in half-strength Hoagland solution), ATP content of "Tanyin 2"
      roots increased under NaCl stress for 2 d, and decreased on 4 d after NaCl
      stress, as compared with control. In "Kepin 7" roots, ATP accumulation was
      inhibited during NaCl stress. Pyrophosphate (PPi) content increased slightly both
      in "Tanyin 2" and "Kepin 7" roots under NaCl stress. Tonoplast H(+)-ATPase
      activity was inhibited competitively by PPi. These results indicated that the
      increase in rate of ATP accumulation might be essential for the stimulation of
      tonoplast H(+)-ATPase activity induced by NaCl. The decrease in ATP content and
      the inhibition of PPi might result in the decrease of tonoplast H(+)-ATPase
      activity in barley roots under NaCl stress.

PMID- 15583409
TI  - [Stomatal and nonstomatal limitations of photosynthesis in mung bean leaves under
      the combination of enhanced UV-B radiation and NaCl stress].
AB  - Stomatal and nonstomatal limitations of photosynthesis in mung bean (Phaseolus
      radiatus L.) leaves under the combination of 0.35 W/m(2) UV-B radiation and 0.4%
      NaCl stress were studied. Separated or combined treatments of enhanced UV-B
      radiation and NaCl stress all resulted in a decrease in net photosynthetic rate,
      stomatal conductance, photosynthetic ability, efficiency of CO(2) carboxylation
      and Rubisco content, and the extent of those decreases enhanced obviously with
      the increase of treatment days. Intercellular CO(2)concentration tended to
      decrease in short period, followed by a gradual increase and to be higher than
      the control on the seventh day after treatment under NaCl stress alone, while a
      tendency of gradual increase was observed under enhanced UV-B radiation alone or
      two stresses combined and the concentration was higher than the control after
      three day of treatments. By contrast, the tendency of stomatal limitation value
      was just reverse to the intercellular CO(2) concentration, but the stomatal
      limitation value was always higher than control under all stress conditions (did
      not include that on the fifth day under the combined stresses). As compared with
      an individual stress the effect of combined stress on the above parameters was
      more serious. These results indicate that under all stress conditions the
      inhibition of photosynthesis in mung bean leaves is the results of both stomatal
      and nonstomatal limitations. And the stomatal limitation is dominant in short
      period, nonstomatal limitation becomes the dominant one in longer period. The
      decrease in Rubisco content leads to nonstomatal limitation of photosynthesis
      under all stresses.

PMID- 15583410
TI  - The role of calcium and calmodulin in freezing-induced freezing resistance of
      Populus tomentosa cuttings.
AB  - To explore the role of calcium-calmodulin messenger system in the transduction of
      low temperature signal in woody plants, Populus tomentosa cuttings after being
      treated with CaCl(2) (10 mmol/L), Ca(2+) chelator EGTA (3 mmol/L), Ca(2+) channel
      inhibitor LaCl(3) (100 mmol/L) or CaM antagonist CPZ (50 mmol/L) were used for
      freezing acclimation at -3 degrees C. The changes in the calmodulin (CaM) and
      malonaldehyde (MDA) contents, the activities of superoxide dismutase (SOD),
      peroxidase (POD) and Ca(2+)-dependent adenosinetriphosphatase (Ca(2+)-ATPase) of
      mitochondrial membrane as well as freezing resistance (expressed as LT(50)) of
      cuttings were investigated to elucidate the physiological mechanisms by which
      trees adapt to freezing. The results showed that freezing acclimation increased
      the CaM content, the activities of SOD, POD and Ca(2+)-ATPase of mitochondrial
      membrane as well as freezing resistance of cuttings, and decreased the MDA
      content as compared with control cuttings. Treatment with CaCl(2) at the time of
      freezing acclimation enhanced the effect of freezing acclimation on the above
      mentioned indexes, but this enhancement was abolished by Ca(2+)chelator EGTA,
      Ca(2+) channel inhibitor LaCl(3) or CaM antagonist CPZ, indicating that the
      calcium-calmodulin messenger system was involved in the course of freezing
      resistance development. The presence of CaCl(2) at the same time of freezing
      acclimation also reduced the degree of decline in CaM content, and in SOD, POD
      and Ca(2+)-ATPase activities caused by freezing stress at -14 degrees C, and
      enhanced the level of increase in CaM content, and in SOD, POD and Ca(2+)-ATPase
      activity in the recovery periods at 25 degrees C . The change in CaM content was
      found to be closely correlated to the levels of SOD, POD and Ca(2+)-ATPase, and
      to the degree of freezing resistance of cuttings during freezing acclimation
      either with or without CaCl(2) treatment. It was suggested that the increase of
      CaM content induced by CaCl(2) treatment promote the formation of Ca(2+)-CaM
      complexes, which effectively activates the activities of SOD, POD and
      mitochondrial Ca(2+)-ATPase and then further result in the adaptive changes
      associated with the development and enhancement of freezing resistance. Thus, It
      could be concluded that Ca(2+)-calmodulin may be involved in the regulation of
      the increase in SOD, POD and Ca(2+)-ATPase activities, and the induction of
      freezing resistance of cuttings.

PMID- 15583411
TI  - [Effects of exogenous spermidine on resistance of Nymphoides peltatum to Hg2+
      stress].
AB  - Effects of different exogenous spermidine concentrations on the activities of
      some enzymes (SOD, CAT, POD, APX), O(-)(2) generation rate, the MDA, chlorophyll,
      soluble protein and polyamine contents in leaves of Nymphoides peltatum without
      Hg(2+) stress or under Hg(2+) stress were studied. The results showed that: (1)
      The spermidine (Spd) and spermine (Spm) content dropped significantly under
      Hg(2+) (3 mg/L) stress 4 d, while that of putrescine (Put) was increased
      markedly. Exogenous Spd could increase the Spd and Spm content in leaves, while
      that of Put lowered at first and rose later. (2) Hg(2+) 3 mg/L decreased
      drastically the activities of SOD, CAT and APX, increased the O(-)(2) generation
      rate, led to the accumulation of a large amount of MDA and loss of chlorophyll
      and soluble protein. Exogenous Spd could enhance the activities of SOD, CAT and
      APX, decrease O(-)(2) generation rate and reduce the MDA content. In addition,
      Spd could also decrease the loss of chlorophyll and soluble protein content
      induced by Hg(2+) stress, enhance the ability of Nymphoides peltatum to resist
      Hg(2+) stress. The most suitable concentration of Spd was in the range 0.1-0.5
      mmol/L.

PMID- 15583412
TI  - [Genetic analysis of a heading-delayed mutant by T-DNA insertion in rice (Oryza
      sativa L.)].
AB  - Transposon tagging was used to isolate genes in higher plant. In this study, a
      delayed heading mutant caused by T-DNA insertion in rice was identified. Genetic
      analysis of the mutant showed that the three types of phenotype, normal heading,
      delayed heading and overly delayed heading in the segregating populations derived
      from the T-DNA heterozygotes fit the ratio of 1:2:1. Test for Basta resistance
      showed the delayed heading plants were all resistant while the normal heading
      plants were susceptible, and the ratio of resistant and susceptible plants was
      3:1, which indicated that the delayed heading mutant was co-segregated with Basta
      resistance. The delayed heading mutant caused by T-DNA insertion was confirmed by
      T-DNA detection using PCR method. This delayed heading mutant will be used for
      isolation of the tagged gene in rice.

PMID- 15583413
TI  - [Expression of OsBP-73 gene requires involvement of its intron in rice].
AB  - It has been demonstrated in our previous work that rice OsBP-73 gene contains two
      exons interrupted by a 2471 bp intron. Here it was reported that the 5' flanking
      region of the ATG translation start codon in the first exon of OsBP-73 gene (from
      -1818 to +215) can not direct GUS gene expression in resistant rice calli or
      transgenic rice. When the complete OsBP-73 intron and its flanking region (from 
      1818 to +2844) are constructed in frame with GUS coding region, GUS activity can
      be detected in the resistant rice calli and transgenic rice. Experimental data
      also show that the complete OsBP-73 intron itself has no promoter activity. These
      results suggest that the OsBP-73 intron sequence is involved in directing the GUS
      gene expression. Another experiment demonstrates that the complete intron
      sequence can enhance the activity of OsEBP-89 gene promoter.

PMID- 15583414
TI  - [Inducible expression of OsEBP-89 gene in rice].
AB  - OsEBP-89 gene was an EREBP (ethylene responsive elements binding protein)
      transcription factor from rice (Oryza sativa). Northern blot analysis revealed
      that the expression of OsEBP-89 gene can be induced by ACC, 2,4-D, ABA, BR, JA,
      GA, 6-BA and salt. We found an ethylene responsive element-like ERE (ethylene
      responsive element), named IVC box, in the promoter region (-552 to -510) of
      OsEBP-89 gene. EMSA results showed the IVC box could specifically bind with
      nuclear proteins extracted from immature rice seeds. When the rice suspension
      cell harboring IVC/35S mini-promoter (-46)/GUS chimeric construct (pIVC/GUS) was
      treated by ACC, GUS activity could be induced. However, two plasmids with OsEBP
      89 promoter/GUS (pPSG) and IVC box-deleted OsEBP-89 promoter/GUS (pSphSG) were
      transformed to rice, when both transgenic suspension cell treated with ACC the
      GUS expression was also inducible. This result indicated that there are more than
      one ethylene-responsive elements located in the promoter region of the OsEBP-89
      gene.

PMID- 15583415
TI  - [Effect of NaCl stress on ion compartmentation, photosynthesis and growth of
      Salicornia bigelovii Torr].
AB  - Seedlings of Salicornia bigelovii Torr. were treated with different
      concentrations of NaCl (0, 100, 300, 600 mmol/L). Ion contents, Na(+) subcelluar
      localization, photosynthetic rate, ultrastructure of chloroplast and other
      parameters were measured. The data showed both fresh and dry weight of whole
      plant of Salicornia bigelovii Torr. under salinity were higher than the control.
      When NaCl concentration is about 300 mmol/L Salicornia bigelovii Torr. grow
      strongest. The contents of Na(+) and Cl(-) and c(Na)/c(K) in shoots increased
      with the salinity. Both Na(+) and Cl(-) were mainly transported to shoots. Ion X
      ray microanalysis indicated Na(+) was mainly compartmentalized into vacuoles.
      Photosynthetic rate increased with the salinity under NaCl 100-300 mmol/L, but
      declined under NaCl 600 mmol/L. Ultrastructure of chloroplast was destroyed by
      NaCl 600 mmol/L.

PMID- 15583416
TI  - [Changes in solute content of different tomato genotypes under salt stress].
AB  - Two wild tomato species Lycopersicon peruvianum LA111, Lycopersicon pennellii
      LA716 and two cultivars "Xianfeng 98-7", "Jiaonong No.1" with different salt
      tolerance were treated with NaCl 150 mmol/L, and to measure the inorganic ions
      Na(+), K(+), Ca(2+) contents and the organic compounds free proline, soluble
      sugar contents. The results indicated that under salt stress, the wild species
      accumulated much Na(+) in young leaves, while cultivated species produced and
      accumulated much free proline and soluble sugar in young leaves, and Na(+) was
      mostly distributed to old leaves. So it can be seen that there are marked
      differences between wild species and cultivars in producing and accumulating
      these solutes under salt treatment. They adapt to salt stress through different
      salt tolerance mechanisms.

PMID- 15583417
TI  - [The structural, transcriptional and homology analysis of two frr genes in rice].
AB  - Two rice (Oryza sativa subsp. japonica cv. Nipponbare) ribosome recycling factor
      genes--OsfrrA and OsfrrB had been identified and characterized in this study. The
      gene OsfrrA is located on chromosome 4 while OsfrrB on chromosome 7. No other
      homologue is found in rice organelle genomes. Both genes are unique in rice
      genome and constitutively expressed. The N-terminal character of their encoded
      protein products suggests that the proteins are transferred to mitochondrion and
      chloroplast respectively and carry out their functions. The sequence conservation
      and the constitutive expression profile of the two genes strongly imply their
      indispensable role in plant growth. In addition, these sequences share
      phylogenetic homology to some extent with other prokaryotic and eukaryotic RRFs,
      providing further evidence for the endosymbiotic theory, and implying the
      potential value of RRFs in molecular evolution research.

PMID- 15583418
TI  - [Synthesis and degradation of the peanut storage proteins during seed development
      and germination].
AB  - Three polypeptides, 41 kD and 38.5 kD subunits of arachin and 60.5 kD subunit of
      conarachin in peanut (Arachis hypogaea L. Shanyou 523) seeds were purified by gel
      filtration and SDS-PAGE. Polyclonal antibodies against these subunits were raised
      in mice. Western blot showed that the subunits appeared in axes and cotyledons at
      the tissue differentiation stage. The 60.5 kD subunit was firstly synthesized and
      accumulated in considerable quantity in axes and cotyledons, and then the 41 kD
      and 38.5 kD subunits increased during the development of peanut embryos. The
      degradation patterns of these three subunits were different during the
      germination of peanut seeds. The 41 kD and 38.5 kD subunits in the axes and
      cotyledons were degraded earlier than the 60.5 kD subunit.

PMID- 15583419
TI  - Craniodental variation in the African macaque, with reference to various Asian
      species.
AB  - Based on twenty-seven craniodental measurements and ratios derived from them, the
      relationship between the African macaque (M. sylvanus) and the others in Asia
      were examined with principal components analyses (PCA) and Euclidean distance
      analysis based upon prior discriminant function analyses (DFA). Results based on
      analyses of raw measurements indicate that the variation between species lies in
      the first axis of PCA; the species are dispersed according to their differences
      in size. The variation between sexes (sexual dimorphism) lies in the second axis.
      In the analyses of ratio variables, though these two patterns of separation
      remain orthogonal, they lie at approximately forty-five degrees to each axis.
      Variables relating to anterior teeth were found to play an important role in
      variation analysis, and this may be related to the special food preferences of
      these monkeys: more frequent usage of the incisor teeth for processing
      frugivorous diets than in other primates that are mainly folivorous. The results
      from Euclidean distance analyses indicate that the average distance of species
      within the Asian group is shorter than that between Asian and African groups
      regardless of sex and variable type. In addition the variation between African
      and Asian groups is larger than that within Asian group. Thus, it is reasonable
      to suggest that the African macaque has a range of measurements and ratios quite
      distinct from the species found in Asia (though the greatest separations result
      from the analyses of ratio data). These results therefore support the view that
      M. sylvanus may be regarded as an independent species group in the genus Macaca
      as proposed by Delson [1980].

PMID- 15583420
TI  - Predation by Eulemur fulvus fulvus on eggs of Ploceus sakalava sakalava (Aves:
      Ploceidae) in Ankarafantsika, Madagascar.

PMID- 15583421
TI  - Inter-group encounters in Western lowland gorillas at a forest clearing.

PMID- 15583422
TI  - Analysis of candidate genes for prostate cancer.
AB  - Considerable evidence demonstrates that genetic factors are important in the
      development and aggressiveness of prostate cancer. To identify genetic variants
      that predispose to prostate cancer we tested candidate SNPs from genomic regions
      that show linkage to prostate cancer susceptibility and/or aggressiveness, as
      well as genes that show a significant difference in mRNA expression level between
      tumor and normal tissue. Cases had histologically verified prostate cancer.
      Controls were at least 65 years old, never registered a PSA above 2.5 ng/ml,
      always had digital rectal examinations that were not suspicious for cancer, and
      have no known family history of prostate cancer. Thirty-nine coding SNPs and nine
      non-coding SNPs were tested in up to 590 cases and 556 controls resulting in over
      40,000 SNP genotypes. Significant differences in allele frequencies between cases
      and controls were observed for ID3 (inhibitor of DNA binding), p = 0.05, HPN
      (hepsin), p = 0.009, BCAS1 (breast carcinoma amplified sequence 1), p = 0.007,
      CAV2 (caveolin 2), p = 0.007, EMP3 (epithelial membrane protein 3), p < 0.0001,
      and MLH1 (mutL homolog 1), p < 0.0001. SNPs in three of these genes (BCAS1, EMP3
      and MLH1) remained significant in an age-matched subsample.

PMID- 15583423
TI  - Approaches to familial aggregation: hypothesis testing and estimation when
      families are selected through parent probands under a variant of single
      ascertainment.
AB  - Epidemiologic approaches to testing and estimating familial aggregation of a
      disease consist of comparing rates of disease in relatives of individuals with
      the disease (known as case probands) with rates of disease in relatives of
      individuals without the disease (known as control probands). Gold et al. (J Am
      Stat Ass 1967;62: 409-420) derived an explicit mathematical model and sampling
      methods, under which this approach is equivalent to testing the null hypotheses
      that the disease risk in families is homogenous. A basic assumption of this model
      is that every family member has the same risk of disease and that disease status
      is independent among family members, although the disease risk may vary between
      families. When the disease is suspected of having a genetic component, rather
      than being purely environmental, this model has been shown to be appropriate for
      detecting disease aggregation in siblings, when relatives are siblings of
      probands. This model however is unrealistic for use in nuclear families when the
      affected status of offspring is not independent of the affected status of
      parents, and these families are selected through an affected or an unaffected
      parent, so that a parent is the proband and relatives are offspring of probands.
      We extend the Gold et al. model to allow for the disease risk in offspring to
      vary with the affected status of the parent. We assume that families are selected
      through affected and unaffected parents, under a variation of single
      ascertainment. Under this study design, we show that the usual test of
      association between affected status of probands and relatives, performed by
      comparing sample proportions of affected relatives of affected and unaffected
      probands, respectively, is no longer equivalent to a test of homogeneity of
      disease risk in offspring. Instead, it is equivalent to testing that the disease
      risk in offspring is independent of the number of affected parents. This test
      reduces to a test of homogeneity if and only if one assumes that the variation in
      disease risk in offspring, between families, is solely due to the variation in
      the number of affected parents. As a result, we show that under this study
      design, the standard chi2 test must be modified in order to obtain a valid test
      of familial aggregation. In addition the sample proportions of affected relatives
      of case and control probands, respectively, are shown to provide unbiased
      estimates of the expected risk of disease in an offspring given an
      affected/unaffected parent. We apply these results to methods of sample selection
      and discuss the practical implications of these findings.

PMID- 15583424
TI  - Reanalysis of a genome scan for schizophrenia Loci using multigenic methods.

PMID- 15583425
TI  - DFNB44, a novel autosomal recessive non-syndromic hearing impairment locus, maps
      to chromosome 7p14.1-q11.22.
AB  - The genetic etiology for many forms of hearing impairment (HI) is very diverse.
      Non-syndromic HI (NSHI) is one of the most heterogeneous traits known. Autosomal
      recessive forms of prelingual HI account for approximately 75% of hereditary
      cases. A novel autosomal recessive NSHI locus, DFNB44, was mapped to a 20.9 cM
      genetic interval on chromosome 7p14.1-q11.22, according to the Marshfield genetic
      map, in a consanguineous Pakistani family. Multipoint linkage analysis resulted
      in a maximum LOD score of 5.0 at marker D7S1818. The 3-unit support interval
      ranged from marker D7S2209 to marker D7S2435, spanning a 30.1 Mb region on the
      sequence-based physical map.

PMID- 15583426
TI  - A note on inference of trait associations with SNP haplotypes and other
      attributes in generalized linear models.
AB  - Recently, Lake et al. [Human Heredity 2003;55:56-65] have proposed an approach
      based on the EM algorithm for maximum-likelihood inference of trait associations
      with haplotypes and environmental cofactors in generalized linear models. In this
      short report, we describe an extension to accommodate missing SNP genotype
      information. We also discuss differences in the calculation of standard errors
      between their implementation and our own. Finally, we present results indicating
      that inference is robust to low levels of dependence between haplotypes and
      nongenetic factors, but that biased inference can result when there is moderate
      to strong dependence. Overall, the method is found to perform well in the models
      we considered.

PMID- 15583427
TI  - On computation of p-values in parametric linkage analysis.
AB  - Parametric linkage analysis is usually used to find chromosomal regions linked to
      a disease (phenotype) that is described with a specific genetic model. This is
      done by investigating the relations between the disease and genetic markers, that
      is, well-characterized loci of known position with a clear Mendelian mode of
      inheritance. Assume we have found an interesting region on a chromosome that we
      suspect is linked to the disease. Then we want to test the hypothesis of no
      linkage versus the alternative one of linkage. As a measure we use the maximal
      lod score Z(max). It is well known that the maximal lod score has asymptotically
      a (2 ln 10)(-1) x (1/2 chi2(0) + 1/2 chi2(1)) distribution under the null
      hypothesis of no linkage when only one point (one marker) on the chromosome is
      studied. In this paper, we show, both by simulations and theoretical arguments,
      that the null hypothesis distribution of Zmax has no simple form when more than
      one marker is used (multipoint analysis). In fact, the distribution of Zmax
      depends on the number of families, their structure, the assumed genetic model,
      marker denseness, and marker informativity. This means that a constant critical
      limit of Zmax leads to tests associated with different significance levels.
      Because of the above-mentioned problems, from the statistical point of view the
      maximal lod score should be supplemented by a p-value when results are reported.

PMID- 15583428
TI  - Linkage analysis using single nucleotide polymorphisms.
AB  - We performed multipoint linkage analysis using 83 markers from the SNP Consortium
      (TSC) SNP linkage map in 3 regions covering 190 cM previously scanned with
      microsatellite markers and found to be linked to type 2 diabetes. Since the
      average linkage disequilibrium present in the TSC SNP marker clusters is
      relatively low, we assumed the intracluster genetic distances were a reasonable
      small nonzero distance (0.03 cM) and performed linkage analysis using GENEHUNTER
      PLUS and ASM linkage analysis software. We found that for the pedigree structures
      and missing data patterns in our samples the average information content in all
      three regions and the LOD score curves in two regions obtained from the TSC SNP
      markers were similar to results obtained from microsatellite marker maps with 10
      cM average spacing. We also give an algorithm which extends the Lander-Green
      algorithm to permit multipoint linkage analysis of clusters of tightly linked
      markers with arbitrarily high levels of intracluster linkage disequilibrium.

PMID- 15583429
TI  - Pathomechanisms of cystoid macular edema.
AB  - Cystoid macular edema (CME) is a well-known endpoint of various ocular diseases,
      but the relative pathogenic impact of extra- and intracellular fluid accumulation
      within the retinal tissue still remains uncertain. While most authors favor an
      extracellular fluid accumulation as the main causative factor of cyst formation,
      there are indications that Muller cell swelling may also contribute to CME
      development (particularly in cases without significant angiographic vascular
      leakage). Vascular leakage occurs after a breakdown of the blood-retinal barrier
      during traumatic, vascular, and inflammatory ocular diseases, and allows the
      serum to get into the retinal interstitium. Since intraretinal fluid distribution
      is restricted by two diffusion barriers, the inner and outer plexiform layers,
      serum leakage from intraretinal vessels causes cysts mainly in the inner nuclear
      layer while leakage from choroid/pigment epithelium generates (in addition to
      subretinal fluid accumulation) cyst formation in the Henle fiber layer. In the
      normal healthy retina, the transretinal water fluxes are mediated by glial and
      pigment epithelial cells. These water fluxes are inevitably coupled to fluxes of
      osmolytes; in the case of glial (Muller) cells, to K(+) clearance currents. For
      this purpose, the cells express a complex, microtopographically optimized pattern
      of transporters and channels for osmolytes and water in their plasma membrane.
      Ischemic/hypoxic alterations of the retinal microvasculature result in gliotic
      responses which involve down-regulation of K(+) channels in the perivascular
      Muller cell end-feet. This means a closure of the main pathway which normally
      generates the osmotic drive for the redistribution of water from the inner retina
      into the blood. The result is an intracellular K(+) accumulation which, then,
      osmotically drives water from the blood into the glial cells (i.e., in the
      opposite direction) and causes glial cell swelling, edema, and cyst formation.
      While the underlying mechanisms await further research, it is expected that their
      improved knowledge will stimulate the development of novel therapeutic approaches
      to resolve edema in retinal tissue.

PMID- 15583430
TI  - Comparison of intraocular pressure measurements with the digital tonometer TGDc
      01 'PRA' and the Goldmann applanation tonometer.
AB  - BACKGROUND: To compare intraocular pressure (IOP) measurements obtained with the
      digital tonometer TGDc-01 'PRA' with those from a Goldmann applanation tonometer
      (GAT). METHODS: The IOP in 176 eyes of 88 healthy volunteers was measured
      prospectively in a sitting position. One single measurement, generated by the
      TGDc-01 PRA, was compared with a single reading from the GAT. RESULTS: Mean IOP
      values were 13.0 +/- 3.7 mm Hg for the TGDc-01 PRA (range, 4-22 mm Hg) and 14.9
      +/- 3.2 mm Hg for the GAT (range, 8-27 mm Hg). The mean difference was 1.9 mm Hg
      with a standard deviation of 2.77 mm Hg, and this was statistically significant
      (p < 0.001, paired t test). CONCLUSIONS: In comparison to the GAT, the TGDc-01
      PRA underestimated IOP on an average of 1.9 mm Hg. Only 50.6% of all measurements
      were within the +/-2 mm Hg difference range. Thus, the TGDc-01 PRA has no high
      coincidence degree with the GAT. Both methods were not equivalent.

PMID- 15583431
TI  - Investigation of the use of positron emission tomography for neuroreceptor
      imaging in rabbit eyes.
AB  - To determine whether positron emission tomography (PET) can be used for imaging
      of neuroreceptors in eyes of rabbits. PET imaging of dopamine D(2) receptor,
      dopamine transporter, serotonin(1A) receptor and sigma(1) receptor in the eyes
      and brain was performed using corresponding positron-emitting ligands in
      baseline, pretreatment and displacement conditions. The 4 radioligands outlined
      the eyes and brain in the baseline. Pretreatment resulted in a slight reduction
      (26-28%) in the uptake in the anterior segments of eyes. The binding of each
      radioligand in the iris-ciliary body and retina was confirmed by ex vivo
      autoradiography. However, the PET signal in the eyes was unexpectedly higher than
      the autoradiography signal. The identification of radioligand-neuroreceptor
      binding by PET in the rabbit eyes is not specific enough.

PMID- 15583432
TI  - Vitamin E can protect against ultraviolet radiation-induced cataract in albino
      rats.
AB  - PURPOSE: To investigate if vitamin E protects against ultraviolet B radiation
      (UVB)-induced cataract. METHODS: Albino Sprague-Dawley rats were divided into two
      groups: one group was fed vitamin E, while the other group was used as a control.
      Both groups were exposed to UVB. The rats were sacrificed, lenses extracted,
      forward light scattering was measured, and vitamin E and glutathione (GSH)
      contents were determined. RESULTS: Lenses in the vitamin E group developed slight
      opacities, while lenses in the control group developed nuclear cataracts. Forward
      light scattering in lenses of the control group was higher than in lenses in the
      vitamin-E-supplemented group. Vitamin E and GSH concentrations were higher in
      lenses treated with vitamin E than in the untreated group. CONCLUSIONS: Vitamin E
      protects the lens against UVB-induced cataract. Vitamin E protects directly as an
      antioxidant and/or indirectly through increased levels of GSH.

PMID- 15583433
TI  - Corneal cell density measurement in vivo by scanning slit confocal microscopy:
      method and validation.
AB  - PURPOSE: Method and validation of a technique to quantify cell density in vivo in
      6 corneal layers with a scanning slit confocal microscope (SSCM). METHOD: A
      confocal image of a small volume in a corneal layer is registered on videotape.
      Cells or nuclei according to a layer classification are counted manually using an
      unbiased frame. Surface cell density is calculated from an image on the screen,
      and volumetric density is obtained using stereological methods. RESULTS: Image
      distortion on the screen is less than 3%. The classification of a cell layer is
      verified by determining the position of the measurement volume in the cornea.
      Validation of density measurements is performed by comparing confocal results
      with those obtained by histology. The difference between the two methods varies
      from -24.1% (posterior stroma) to +16.4% (basal layer). Intersession and
      intrasession repeatability are 8.3 and 5.8%, respectively. The cell density (mean
      +/- SD) in 20 healthy controls in the superficial, basal and endothelial layers
      was 759 +/- 162, 5,817 +/- 632 and 2,743 +/- 285 cells.mm(-2) (surface), and in
      the anterior, mid and posterior stroma 28,616 +/- 3,081, 19,578 +/- 4,421 and
      26,073 +/- 5,962 cells.mm(-3) (volumetric). These results are in accordance with
      those of other investigators. CONCLUSIONS: The SSCM can produce repeatable
      quantitative measurements of corneal cell density in conscious humans.

PMID- 15583434
TI  - Ultraviolet B-induced corneal and lens damage in guinea pigs on low-ascorbic acid
      diet.
AB  - To evaluate ocular morphological response to ultraviolet B (UV-B) exposure in
      guinea pigs fed with normal and low-ascorbic acid (ASA) diets, 24 guinea pigs
      were randomly divided into UVR (normal diet + UV-B), LVC (low-ASA diet + UV-B)
      and CTL (normal diet, without UV-B) groups. The irradiated animals were exposed
      to 8.2 J/cm(2) of UV-B over 29 weeks. Changes in the cornea and lens were
      examined using a Scheimpflug camera, specular microscope and histological
      studies. ASA contents in the plasma, aqueous humor and lens sections were
      measured by high-performance liquid chromatography. The results showed low
      contents of ASA in the plasma, aqueous humor and lens sections in LVC. Both
      irradiated groups displayed corneal epithelial edema, neovascularization in
      stroma, increase in corneal thickness, decrease in endothelial density, and lens
      epithelial damage. No significant morphological differences in cornea and lens
      were found between guinea pigs fed with low-ASA or normal diet.

PMID- 15583435
TI  - Why promote an educational process for separating level II into level IIA and
      level IIB in neck dissection?

PMID- 15583436
TI  - Genotyping of Streptococcus pneumoniae and Haemophilus influenzae isolated from
      paired middle ear fluid and nasopharynx by pulsed-field gel electrophoresis.
AB  - Twenty-eight isolates of Streptococcus pneumoniae and 30 isolates of Haemophilus
      influenzae from paired nasopharynx and middle ear fluids of 21 children with
      acute otitis media (AOM) were evaluated to determine genotypes by polymerase
      chain reaction and pulsed-field gel electrophoresis (PFGE). Among the 28 isolates
      of S. pneumonaie, 21 isolates (75.0%) possessed mutations in the pbp1a,pbp2x, and
      pbp2b genes, and 7 isolates (25%) had mutations in the pbp2x gene. Nineteen
      isolates (67.9%) expressed the mefE gene, and 5 isolates (17.9%) possessed the
      ermB gene. Among the 30 isolates of H. influenzae, 5 isolates (16.7%) had
      mutations in pbp3 genes, 3 isolates (10.0%) produced beta-lactamase, and 2 (6.7%)
      isolates possessed mutations both in the pbp3 gene and the beta-lactamase gene.
      Ten out of the 14 pairs (71.4%) of the restriction fragment patterns of S.
      pneumoniae from paired nasopharynx and middle ear fluids were indistinguishable
      following PFGE analysis. The same patterns were identified among 5 children of
      unrelated families. The restriction fragment patterns of H. influenzae isolated
      by PFGE were also indistinguishable in 13 out of the 15 pairs (86.7%) of
      nasopharynx and middle ear fluids. The genetic similarity between nasopharyngeal
      and middle ear isolates suggests that the causative bacteria migrate from the
      nasopharynx into the middle ear cavity via the Eustachian tube. Some resistant
      strains might be prevalent. In children with AOM, the nasopharynx could have been
      colonized by a virulent strain of bacteria that replaced the benign, commensal
      bacteria and then progressed to the middle ear, where they caused AOM.

PMID- 15583437
TI  - Head and neck cancer susceptibility: a genetic marker in the
      methylenetetrahydrofolate reductase gene.
AB  - Progress in the elucidation of molecular genetic changes that lead to the
      development of tumors should soon bring novel diagnostic and therapeutic
      procedures into clinical practice. In this respect, methylenetetrahydrofolate
      reductase (MTHFR) plays a central role in folate metabolism that affects DNA
      methylation and synthesis. DNA methylation is an epigenetic feature that
      influences cellular development and function. Germ line mutation C>T at
      nucleotide 677 of the MTHFR gene, which results in increased thermolability and
      diminished enzyme activity, is oncogenic, i.e. should be a contributor to
      molecular changes leading to cancerous phenotypes (it has also been shown
      independently to be implicated in cardiovascular disease phenotypes).
      Interestingly, it has been shown that MTHFR T677 allele homozygosity confers a
      sixfold increased risk for esophageal squamous cell carcinoma in Northern China.
      The purpose of this study was twofold: (1) to evaluate the putative association
      of MTHFR C677T and epithelial squamous cell carcinoma (ESCC) in Pakistan, and (2)
      to investigate whether de novo MTHFR C677T mutations are involved in the
      determination of ESCC phenotypes. We recruited 50 ESCC patients referred to the
      Otolaryngology Clinic of the Aga Khan University Hospital, and 54 age- and gender
      matched control (disease-free) subjects. Our results show that T allele
      frequencies were 0.18 +/- 0.05 in cases vs. 0.24 +/- 0.05 in controls (as
      compared with 0.63 vs. 0.41 in the report from China). Although the association
      is not statistically significant, T alleles are actually more common amongst
      controls in the Pakistani population, which is the opposite of what would be
      expected and what has been reported amongst Chinese. Yet the frequency of
      deleterious T alleles is lower in Pakistan (range 0.18-0.24) than in other parts
      of the world. Our results indicate that MTHFR C677T cannot form the basis for a
      genetic test aimed at evaluating an individual's genetic susceptibility to ESCC
      in Pakistan. As the conversion of precancerous submucous fibrosis into overt
      cancer is a frequent occurrence in Pakistan, we proceeded to extract DNA samples
      in all ESCC patients, from whole blood, cancerous tissues and neighboring normal
      tissues. We sought to determine whether C677T genotypes were different in the
      three tissue samples from each ESCC patient. In all patients, identical genotypes
      (and therefore allele frequencies) were systematically observed in all three
      samples. This indicates that de novo MTHFR 677TC>T mutations are not part of the
      molecular etiology of ESCC. In conclusion, we can rule out a major involvement of
      the MTHFR gene in the determination of ESCC in Pakistan.

PMID- 15583438
TI  - The characteristic features of muscle tension dysphonia before and after surgery
      in benign lesions of the vocal fold.
AB  - Muscular tension dysphonia (MTD) is often concomitant in patients with underlying
      glottic insufficiency. It remains unclear, however, whether the characteristic
      features of MTD appear independently or as a consequence of dysphonia. We report
      here on a retrospective study of the prevalence of the four prominent
      characteristic features of MTD, as described by the Morrison-Rammage
      classification, in patients with benign lesions of the vocal fold. Two
      otorhinolaryngologists, independent of one another, rated the preoperative and
      postoperative videolaryngostroboscopic results of 260 patients to assess the
      presence or absence of MTD. Of the 260, 185 had vocal nodules, 49 had vocal
      polyp, and 26 had vocal cyst. Postoperative follow-up examinations were conducted
      for a period ranging from 4.5 to 35 months (mean = 18.5 months). Patient ages
      ranged from 18 to 76 years (mean = 47.3 years). Nearly 90% of the preoperative
      patients in our study cohort exhibited at least one of the MTD characteristic
      features. Approximately 74% of postoperative 'asymptomatic' patients in our study
      cohort exhibited at least one characteristic feature. As the characteristic
      features of MTD were found in both preoperative dysphonic patients and those
      patients who were successfully treated, MTD etiology may be causal (type I),
      concomitant (type IIa, IIb, III) or psychogenic (type IIa, IIb). Therefore
      characteristic features of MTD cannot be adequately resolved through surgery, and
      treatment should be supplemented by speech therapy to achieve the greatest effect
      in causal type I MTD.

PMID- 15583439
TI  - Mandarin speech perception in nucleus CI 24 implantees using MAPs based on neural
      response telemetry.
AB  - The purpose of this study is to compare speech perception performance in Mandarin
      speaking Nucleus CI24 implantee using standard behavior MAPs and NRT-based MAPs.
      Eight Nucleus CI24 users (5 years and older) participated in the study. They all
      fulfilled the following criteria: (1) behavioral MAP and NRT thresholds can be
      reliably obtained; (2) had more than 18 functioning electrodes; (3) had at least
      6 months experience using CI. All subjects received speech evaluation under three
      different MAPs: a traditional behavioral MAP, a MAP predicted from the NRT
      thresholds of the E22 (electrode 22), E19, E15, E11, E8, E5, E1 and a combined
      MAP based on the information of NRT thresholds and behavioral
      threshold/comfortable levels of the E11. The speech evaluation package included
      word recognition test in quiet, in noise, and a Mandarin sentence test in quiet.
      Results showed that three MAPs are similar in some subjects, but different in
      other subjects. Compared to the NRT MAPs, the combined MAPs are more similar to
      the behavioral MAPs. There was no significant difference in the mean score of the
      word recognition test in quiet, in noise and sentence test under these three MAP
      conditions. In conclusion, although the behavioral MAPs and the NRT-based MAPs
      are not identical, the speech performance of Mandarin-speaking CI24 implantee
      using MAPs predicted from NRT thresholds appeared to be no worse than the
      traditional behavioral MAPs. Therefore, in certain cases that behavioral MAPs are
      difficult to obtain (such as in very young or multiple handicapped children), NRT
      based MAPs may serve reliably as an initial estimation.

PMID- 15583440
TI  - Use of cross-sectional imaging in predicting facial nerve sacrifice during
      surgery for parotid neoplasms.
AB  - BACKGROUND: Neoplasms of the parotid gland are difficult management issues
      because of the wide variation in their biological behavior and the potential for
      sacrifice of the facial nerve during resection. Because of the significant
      associated morbidity, prediction of facial nerve sacrifice is critically
      important for planning surgical procedures and preoperative counseling of
      patients. We hypothesize that along with the knowledge of the tumor type we would
      be able to accurately predict the likelihood of facial nerve sacrifice using
      cross-sectional imaging. METHODS: All patients included in this study were
      previously untreated patients with parotid neoplasms operated on between January
      1997 and July 2002. Only those patients with an available preoperative imaging
      were included and this resulted in 44 patients for review. Nine patients with
      preoperative deficits in facial nerve function were excluded from this study
      since these patients would require facial nerve sacrifice regardless of the
      radiological prediction. The prediction of facial nerve sacrifice was determined
      using a prediction of tumor location and an algorithm. The predicted results were
      compared to the operative record. RESULTS: For all lesions, cross-sectional
      imaging predicted the need for sacrifice of the facial nerve with a sensitivity
      of 0.83 (95% CI, 0.36-0.99), specificity of 0.90 (95% CI, 0.72-0.97), PPV of 0.63
      (95% CI, 0.26-0.90), and NPV of 0.96 (95% CI, 0.79-0.99). For malignant lesions
      only, prediction of sacrifice of the facial nerve had a sensitivity of 0.83 (95%
      CI, 0.36-0.99), specificity of 0.80 (95% CI, 0.51-0.95), PPV of 0.63 (95% CI,
      0.26-0.90), and NPV of 0.92 (95% CI, 0.62-0.99). CONCLUSION: Cross-sectional
      imaging and application of our algorithm is a sensitive method for identifying
      patients with parotid neoplasms who require facial nerve sacrifice. CT and MRI
      have a high negative predictive value for facial nerve sacrifice.

PMID- 15583441
TI  - Electronic videoendoscopic laryngostroboscopy.
AB  - Color images obtained using electronic videoendoscopic laryngostroboscopy (EVLS)
      were presented and the utility of this technique for the diagnosis of dysphonia
      was discussed in this paper. Stroboscopic evaluations of laryngeal lesions were
      performed using a rhinolaryngeal electronic videoendoscope system employing a
      single-plate simultaneous color charge-coupled device (CCD) chip method. Twenty
      patients underwent electronic videoendoscopic laryngostroboscopy. A Karl Storz
      laryngostroboscope Pulsar was connected to this system and laryngeal lesions were
      assessed. The potentialities of laryngostroboscopy using this system were
      evaluated. Clear stroboscopic images were obtained in all patients. Multiple
      still images during vocal fold vibration were acquired using an optional
      function. The laryngostroboscope is not compatible with conventional systems
      employing a single-plate red, green, and blue (RGB) surface scanning method.
      However, the system used was successfully connected to a laryngostroboscope. EVLS
      appears to be a powerful new tool for the diagnosis of dysphonia.

PMID- 15583442
TI  - Mycobacterial cervical lymphadenitis.
AB  - Cervical lymphadenitis is the most common head and neck manifestation of
      mycobacterial infections. The incidence of mycobacterial cervical lymphadenitis
      has increased. It may be the manifestation of a systemic tuberculous disease or a
      unique clinical entity localized to neck. It remains a diagnostic and therapeutic
      challenge because it mimics other pathologic processes and yields inconsistent
      physical and laboratory findings. A high index of suspicion is needed for the
      diagnosis of mycobacterial cervical lymphadenitis. A unilateral single or
      multiple painless lump, mostly located in posterior cervical or supraclavicular
      region can occur. A thorough history and physical examination, tuberculin test,
      staining for acid-fast bacilli, radiologic examination, fine-needle aspiration
      and PCR will be instrumental in arriving at an early diagnosis early institution
      of treatment before a final diagnosis can be made by biopsy and culture. It is
      important to differentiate tuberculous from nontuberculous mycobacterial cervical
      lymphadenitis because their treatment protocols are different. Tuberculous
      adenitis is best treated as a systemic disease with antituberculosis medication.
      Atypical infections can be addressed as local infections and are amenable to
      surgical therapy.

PMID- 15583443
TI  - Progressive bilateral sensorineural hearing loss induced by an antithyroid drug.
AB  - We report a patient with antithyroid drug-induced progressive bilateral
      sensorineural hearing loss associated with myeloperoxidase-antineutrophil
      cytoplasmic antibodies (MPO-ANCA). While antithyroid drugs have been linked to
      MPO-ANCA-associated small-vessel vasculitis, sensorineural hearing loss rarely
      was noted. A 36-year-old man treated for hyperthyroidism with propylthiouracil
      (PTU) developed progressive bilateral sensorineural hearing loss accompanied by
      fever and arthritis. MPO-ANCA were demonstrated in serum. Distortion product
      otoacoustic emissions test results suggested dysfunction of outer hair cells of
      the organ of Corti. Inner ear blood flow impairment from ANCA-associated small
      vessel vasculitis presumably caused cochlear dysfunction. PTU withdrawal and high
      dose methylprednisolone administration greatly improved hearing on both sides.

PMID- 15583444
TI  - Transglottic acinic cell carcinoma. Case report and literature review.
AB  - Acinic cell carcinoma (ACC) is a rare tumor generally involving the parotid gland
      and infrequently the minor salivary glands with the potential for both local
      recurrence and metastatic spread when tracked for decades. The biological
      behavior of ACC cannot be predicted on the basis of histological features, and
      surgical stage is still the best predictor of clinical outcome. Only 5 cases of
      ACC of the larynx have been reported in the English literature. The authors
      present a case of a rare transglottic ACC in a 74-year-old woman. At admission, a
      submucosal mass involving the left arytenoid and adjacent aryepiglottic fold was
      noted. A CT scan of the head and neck region showed a mass of the left hemilarynx
      involving the paraglottic space and extending from the aryepiglottic fold to the
      sinus piriformis. Definitive histopathological examination showed an ACC with a
      large amount of clear cells. The patient was treated by radiotherapy alone (66 Gy
      in 7 weeks) with complete remission.

PMID- 15583445
TI  - Inner ear dysplasia in Levy-hollister syndrome.

PMID- 15583446
TI  - The ecarin clotting time, a universal method to quantify direct thrombin
      inhibitors.
AB  - The ecarin clotting time (ECT) is a meizothrombin generation test that allows for
      precise quantification of direct thrombin inhibitors. The ECT has demonstrated
      its usefulness for more than 10 years in biochemical-pharmacological
      investigations as well as in clinical research and in the clinical routine. It
      has proved valuable especially as a drug-monitoring method in r-hirudin therapy.
      This test has been adjusted to clinical requirements by numerous modifications.
      Following the description of the biochemical background and the measuring
      principle of the ECT, this article gives a short survey of several modifications
      of the ECT for both preclinical and clinical use, e.g., for biochemical
      investigations, as a point-of-care method and for cardiac surgery. Advantages and
      disadvantages of these methods are discussed.

PMID- 15583447
TI  - Ecarin chromogenic assay--a new method for quantitative determination of direct
      thrombin inhibitors like hirudin.
AB  - A new sensitive and precise method for quantitative determination of direct
      thrombin inhibitors is described, the ecarin chromogenic assay (ECA). Ecarin is
      used as the specific prothrombin-activating principle. The cleavage of a
      chromogenic substrate by meizothrombin is inhibited in a concentration-dependent
      fashion by direct thrombin inhibitors. For the ECA, the linear measuring range is
      about 0.1-3.0 microg hirudin/ml plasma. Coefficients of variations between 2.3
      and 4% over the whole concentration range were achieved. The ECA has proved to be
      more sensitive than the compared tests (ecarin clotting time and a thrombin-based
      chromogenic assay); a detection limit of 0.011 microg hirudin/ml and a
      quantitation limit of 0.032 microg hirudin/ml were calculated. The ECA is
      independent of the variations of the coagulation variables fibrinogen and
      prothrombin. Neither heparin nor oral anticoagulants interfere with the ECA.

PMID- 15583448
TI  - Acquired and inherited thrombophilic factors and the risk for residual venous
      thrombosis.
AB  - Acquired and inherited thrombophilic factors increase the risk for (recurrent)
      venous thrombotic disease. However, little is known about the pathophysiological
      mechanisms causing these recurrences, or the persistence of thrombosis despite
      adequate treatment. Because residual thrombosis has been associated with a worse
      prognostic outcome, we performed an explorative study in order to investigate the
      prevalence of residual thrombotic lesions after anticoagulant treatment in
      patients with deep venous thrombosis. Thrombotic parameters as assessed by
      ultrasonography after a 12-week course of anticoagulants were used. Both
      thrombophilia in general and acquired thrombophilia in particular were found to
      be associated with the extent of residual thrombosis. Of the individual
      thrombophilic factors, protein C deficiency, prothrombin 20210A mutation, active
      malignant disease and lupus anticoagulant were associated with an increased risk
      of residual thrombotic mass. Patients with inherited thrombophilia did not differ
      from patients without any thrombophilic abnormality with regard to residual
      thrombotic mass [relative risk (RR) 1.3, 95% confidence interval (CI) 0.9-1.8],
      while acquired thrombophilic disorders increased the risk for residual thrombotic
      mass as compared to patients without any defect (RR 1.7, 95% CI 1.2-2.2).
      Although these results should be confirmed in a larger study, they might help us
      form hypotheses concerning why patients with thrombophilia are more prone to
      recurrent venous thromboembolic disease.

PMID- 15583449
TI  - Low-molecular-weight heparin and cancer survival: review of the literature and
      pooled analysis of 1,726 patients treated for at least three months.
AB  - BACKGROUND: Heparin has been the main subject of intensive investigation and
      clinical use because of its therapeutic anticoagulant properties. It also
      exhibits many other biological activities, and it was claimed that it shows a
      beneficial effect on cancer spreading. Searching for papers investigating the
      effect of low-molecular-weight heparin (LMWH) on cancer mortality we found
      clinical trials and meta-analyses which showed a reduction in the mortality rate
      in cancer patients. However, the biological rationale of this effect for a short
      treatment with LMWH remains unclear. We wanted to check if similar results were
      achieved in cancer patients treated with LMWH for a longer period of time. AIM:
      To evaluate the effect on cancer mortality of a 3-month treatment with LMWH by
      performing a meta-analysis of published studies comparing LMWH and oral
      anticoagulants (OA) in the prevention of recurrent venous thromboembolism (VTE).
      MATERIALS AND METHODS: Computerized searches of Medline and Embase were
      performed; clinical trials were also located through colleagues and hand scanning
      of meeting proceedings. Eligibility of the studies and extraction of data were
      performed by two authors using a standard form. The meta-analysis was performed
      assuming a fixed-effect model. RESULTS: Eight studies were identified that
      fulfilled our predefined criteria for a total of 1,726 patients. After a mean of
      8.6 months of follow-up, 327 patients had died of cancer, 160 in the LMWH group
      and 167 in the OA control group (OR 0.95, 95% CI 0.73-1.23; z = 0.42; p = 0.67).
      Considering cancer mortality in 948 cancer patients the figures were 160/472 in
      the LMWH group and 167/476 in the OA control group (OR 0.96, 95% CI 0.73-1.25; z
      = 0.33; p = 0.74). CONCLUSIONS: In 1,726 patients randomized to receive a long
      term course of at least 3 months of LMWH or OA for the treatment of VTE, no
      effect on cancer mortality was found.

PMID- 15583450
TI  - Normal functional protein S activity does not exclude protein S deficiency.
AB  - Protein S (PS) deficiency appears to increase the risk of venous thrombosis. PS
      deficiency is classified into three phenotypes using antigenic levels and
      functional activity. By definition, all three phenotypes of PS deficiency should
      result in low activated protein C cofactor activity. We compared the results of
      functional PS activity testing to free antigenic PS testing in order to determine
      if a normal functional PS activity assay result could eliminate the need for free
      antigenic PS testing. The sensitivity of the functional assay is 45.5% (95%
      confidence interval, CI, 36-55%), specificity 95.3% (95% CI 93-97%), negative
      predictive value 88.6% (95% CI 86-91%) with a positive predictive value of 68.5%
      (95% CI 57-79%). In conclusion, a normal functional PS activity result does not
      exclude free antigenic PS deficiency. Functional PS activity testing should not
      be used as a screening test to eliminate free antigenic PS testing for the
      laboratory diagnosis of PS deficiency.

PMID- 15583451
TI  - Lack of plasminogen activator inhibitor-1 enhances the preventive effect of DX
      9065a, a selective factor Xa inhibitor, on venous thrombus and acute pulmonary
      embolism in mice.
AB  - We have studied the physiological effects of DX-9065a, a selective factor Xa
      (FXa) inhibitor, and heparin in experimental venous thrombus and acute pulmonary
      embolism. Moreover, the effects of these compounds were also evaluated under the
      condition of plasminogen activator inhibitor-1 (PAI-1) deficiency. A thrombus was
      induced in the murine femoral vein. The compounds prolonged the time to occlusion
      in a dose-dependent manner. Pulmonary embolism was induced by continuous
      induction of venous thrombi in the left jugular vein. The mortality of mice
      increased time-dependently. Histological evidence of thromboembolism in the lung
      was obtained in all mice. Treatment with DX-9065a, but not heparin, reduced the
      mortality at 6 h after initiation of venous thrombi. In separate experiments,
      pulmonary thromboembolism was induced in PAI-1 knockout mice. The mortality in
      PAI-1 knockout mice was reduced compared with that of wild-type mice. Moreover,
      when DX- 9065a was administered to PAI-1 knockout mice with pulmonary
      thromboembolism, mice survived well without marked bleeding. These findings
      indicate that the dual inhibition of coagulation FXa and PAI-1 could be
      beneficial in the treatment of acute pulmonary embolism.

PMID- 15583452
TI  - Alterations of the global haemostatic function test 'resonance thrombography' in
      spontaneously traumatised dogs.
AB  - Samples taken from 30 dogs with spontaneously acute trauma were investigated with
      two different resonance thrombographs (instrument 2: 28 dogs), a global method
      for examination of the haemostatic system. Reaction time of the resonance
      thrombogram (RTG-r), fibrin generation time (RTG-f), fibrin amplitude (RTG-F) and
      parameters of platelet function [amplitude of the platelet leg (RTG-P) and
      descending time of the platelet leg (RTG-p)] were evaluated statistically and
      compared with a normal control as well as with the results of individual
      components of the haemostatic system and other screening tests. Comparison of the
      results of the RTG of dogs suffering from trauma with the normal control revealed
      differences only for RTG-r, which was longer when measured with instrument 1 and
      lower RTG-F values measured with both instruments. Depending on the RTG parameter
      and instrument, only 1-6 samples showed values outside the reference ranges. Only
      4 out of 26 cases (resonance thrombograph 2: 2 out of 24 cases) with mild to
      moderate deficiency in individual coagulation factor activity showed a
      prolongation of RTG-r which was significantly less sensitive than activated
      partial thromboplastin time (p < 0.001). Of the 26 samples having mainly mildly
      to moderately increased fibrin(ogen) degradation product (FDP) levels (median: 39
      microg/ml, range: 2-90 microg/ml, reference values: <18 microg/ml) only between 1
      and 5 showed abnormalities of the parameters RTG-f and/or RTG-F. The results of
      this study show in particular the limited sensitivity of the method for detecting
      individual coagulation factor deficiencies and minimal to moderate increases of
      FDP concentrations. Remarkable alterations of fibrin generation as measured by
      the resonance thrombograph are a rare condition in dogs with acute accidental
      trauma.

PMID- 15583453
TI  - Relationship between hemostatic markers and circulating biochemical markers of
      collagen metabolism in patients with aortic aneurysm.
AB  - Our objective was to determine the relationship between plasma levels of
      hemostatic molecular markers--D-dimer and thrombin-antithrombin III complex (TAT)
      -and circulating biochemical markers of collagen metabolism--aminoterminal
      propeptide of type III procollagen (PIIIP) and carboxyterminal propeptide of type
      I procollagen (PICP)--in patients with aortic aneurysm. The subjects were 43
      patients with aortic aneurysm (AA; mean age 71 years) and 26 age-matched controls
      (mean age 75 years). The mean D-dimer, TAT and PIIIP levels were higher in the
      patients than in the controls (p < 0.0001, 0.0001 and 0.012, respectively), while
      the mean PICP level was similar to that in the controls. Increased D-dimer had a
      significant correlation with PIIIP (r = 0.412, p = 0.006) and PICP (r = 0.342, p
      = 0.0246), while TAT correlated with PIIIP (r = 0.3194, p = 0.0374), but not with
      PICP. There was also a significant correlation (r = 0.306, p = 0.0463) between
      PIIIP and PICP. As shown by the significant positive correlations among D-dimer,
      TAT and PIIIP, accelerated fibrinolysis and thrombogenesis induce an increase of
      collagen degradation and procollagen synthesis in atherosclerotic lesions. These
      findings show that D-dimer and TAT, especially the former, may be useful markers
      to monitor the progression and predict the prognosis of AA.

PMID- 15583454
TI  - Complications of hydroxyethyl starch in acute ischemic stroke and other brain
      injuries.
AB  - Serious complications of hydroxyethyl starch (HES) administration have been
      repeatedly demonstrated in clinical trials of acute ischemic stroke and other
      brain injuries. Such complications have prompted the premature termination of
      several randomized trials. Coagulopathy and bleeding have been the most
      frequently documented complications in the brain injury setting and have occurred
      after exposure to HES solutions of widely varying molecular weight and
      substitutions. Severe, protracted, refractory pruritus is another HES
      complication. Claims of safety for HES solutions have often been made on the
      basis of small trials with inadequate statistical power. Additionally, the safety
      has been typically assessed in highly selected low-risk patient populations
      receiving relatively small HES doses, so that the results cannot be generalized
      to routine clinical practice. The preponderance of available evidence suggests
      that HES solutions should be avoided in acute ischemic stroke and other brain
      injuries.

PMID- 15583456
TI  - T-cell receptor-mediated cross-allergenicity.
AB  - BACKGROUND: Profilins are conserved and ubiquitous plant and animal proteins. We
      wanted to discover whether the T-cell response to conserved epitopes on birch and
      grass profilins could account for cross-allergenicity in subjects allergic to
      these two pollens. METHODS: Thirty-one patients allergic to grass and birch were
      recruited for the study. Grass and birch reactive T lymphocytes were studied by
      measuring proliferation to birch and grass allergen, respectively, followed by
      Vbeta T-cell receptor family-specific polymerase chain reaction and heteroduplex
      analysis. T-cell clones were derived from patients with cross-proliferating T
      cells. RESULTS: In 25 of 31 subjects the T-cell response to grass was quite
      distinct from that to birch. In contrast, in 6 of 31 individuals grass T cells
      cross-proliferated to birch and this was reproduced in 4 patients by birch
      profilin. CD4 Th2 cell clones were derived which promiscuously recognized
      homologously conserved regions on birch and grass profilins. CONCLUSION: We
      conclude that a functionally relevant T-cell response to conserved regions of
      panallergens underlie cross-allergenicity in a subset of allergic patients. These
      results suggest that a reciprocal modulation of the response to one sensitizing
      allergen can occur following natural exposure to or immunotherapy with another
      allergen. These results have relevance in the management of patients with
      multiple allergies.

PMID- 15583457
TI  - Transition from a botanical to a molecular classification in tree pollen allergy:
      implications for diagnosis and therapy.
AB  - Tree pollens are among the most important allergen sources. Allergic cross
      reactivity to pollens of trees from various plant orders has so far been
      classified according to botanical relationships. In this context, cross
      reactivities to pollens of trees of the Fagales order (birch, alder, hazel,
      hornbeam, oak, chestnut), fruits and vegetables, between pollens of the
      Scrophulariales (olive, ash, plantain, privet, lilac) and pollens of the
      Coniferales (cedar, cypress, pine) are well established. The application of
      molecular biology methods for allergen characterization has revealed the
      molecular nature of many important tree pollen allergens. We review the spectrum
      of tree pollen allergens and propose a classification of tree pollen and related
      allergies based on major allergen molecules instead of botanical relationships
      among the allergenic sources. This molecular classification suggests the major
      birch pollen allergen, Bet v 1 as a marker for Fagales pollen and related plant
      food allergies, the major olive pollen allergen, Ole e 1, as a possible marker
      for Scrophulariales pollen allergy and the cedar allergens, Cry j 1 and Cry j 2,
      as potential markers for allergy to Coniferales pollens. We exemplify for Fagales
      pollen allergy and Bet v 1 that major marker allergens are diagnostic tools to
      determine the disease-eliciting allergen source. Information obtained by
      diagnostic testing with marker allergens will be important for the appropriate
      selection of patients for allergen-specific forms of therapy.

PMID- 15583458
TI  - The clinical syndrome associated with lumbar spinal stenosis.
AB  - Lumbar spinal stenosis is well defined in patho-anatomical terms but its clinical
      features are heterogeneous. We carried out a comprehensive retrospective review
      of the clinical features, radiological changes and outcome of 75 patients with
      radiologically diagnosed lumbar spinal stenosis in order to define its clinical
      spectrum. The presenting complaints were of weakness, numbness/tingling,
      radicular pain and neurogenic claudication in almost equal proportions. The
      commonest symptom was numbness or tingling of the legs. Neurogenic claudication
      eventually occurred in only 61%. Ninety-three per cent showed abnormalities on
      neurological examination, but these were generally mild with reduced ankle jerks
      being commonest. Imaging of the lumbar spine showed that moderate to severe
      central spinal stenosis correlated with complaints of weakness and abnormal motor
      power on clinical examination. Patients were reviewed at a mean of 4 years after
      diagnosis and 65% had undergone surgical decompression; this was not a
      prospective comparison of different treatment modalities. Overall, a third of
      patients felt that their symptoms had improved while a quarter felt that they had
      worsened. More than half had satisfactory neurological function at the time of
      review. Thirty-nine per cent of those treated surgically, and 25% of those
      managed conservatively, reported improved symptoms. A poorer functional status at
      review correlated with complaints of motor weakness and associated comorbid
      disease. Degenerative lumbar stenosis is a clinically heterogeneous neurological
      disorder of the lower limbs in the elderly with variable longer-term outcome. A
      high index of suspicion is required and neuroimaging should be obtained to
      confirm the diagnosis.

PMID- 15583459
TI  - Stent grafting resolved brachial plexus neuropathy due to cervical arteriovenous
      fistula.

PMID- 15583460
TI  - Object use impairment associated with left anterior thalamic infarction.

PMID- 15583461
TI  - Isolated abducens nerve palsy due to anterolateral pontine infarction.

PMID- 15583462
TI  - Sensory polyneuropathy as initial manifestation of endemic leprosy in Spain.

PMID- 15583463
TI  - Clinicopathological features influencing pelvic lymph node metastasis and vaginal
      and parametrial involvement in patients with carcinoma of the cervix.
AB  - PURPOSE: This study was undertaken to evaluate clinical and pathologic findings
      that predicted pelvic lymph node metastasis and parametrial and vaginal
      involvement in patients with stage IB carcinoma of the cervix. METHODS: 71
      patients with diagnosis of stage IB (FIGO) cervical cancer were prospectively
      studied from December 1997 to August 2002. The patient's age, clinical stage (IB1
      or IB2), histological classification, grade of differentiation, tumor volume, and
      lymphatic vascular space invasion (LVSI) were evaluated. Statistical methods
      included chi2 test and Fisher's exact test to evaluate significant differences
      between the groups. The level of significance was set at p < 0.05. RESULTS: The
      clinical stage was IB1 in 51 patients (71.8%) and IB2 in 20 patients (28.2%). The
      histological classification identified squamous cell carcinoma in 60 patients
      (84.5%) and adenocarcinoma in 11 patients (15.5%). The average tumoral volume was
      22.8 +/- 24.3 cm3 (0.3-140.0 cm3). The tumor was well differentiated (G1) in 8
      (11.3%), moderately differentiated (G2) in 40 (56.3%) and poorly differentiated
      in 23 (32.4%) of the cases. The presence of LVSI was detected in 14 patients
      (19.7%) and was associated with pelvic lymph node metastasis and vaginal and
      parametrial involvement (p = 0.002, p = 0.001 and p < 0.001; respectively). The
      average number of positive pelvic lymph nodes was significantly higher in the
      patients with LVSI compared with patients without LVSI (2.47 +/- 2.8 vs. 0.33 +/-
      0.74; p = 0.001). There was no association of age, clinical stage, histological
      classification, grade of differentiation or tumor volume with pelvic lymph node
      metastasis and vaginal and parametrial involvement. CONCLUSION: The presence of
      LVSI is significantly associated with pelvic lymph node metastasis and vaginal
      and parametrial involvement in patients with stage IB cervical carcinoma.

PMID- 15583464
TI  - Neurovascular decompression in trigeminal neuralgia: role of intraoperative
      neurophysiological monitoring in the learning period.
AB  - This paper deals with the first 45 consecutive patients undergoing microvascular
      decompression (MVD) surgery for trigeminal neuralgia, studied with perioperative
      brainstem auditory evoked potentials (BAEPs) and electromyography (EMG). We
      observed a good correlation between the intraoperative BAEP modifications and
      postoperative hearing function. BAEP monitoring was useful in identifying the
      manoeuvres that may compromise cochlear nerve function. This improved the
      surgical technique in the subsequent cases and reduced the incidence of
      iatrogenic hearing deficits after the learning period. There were no correlations
      between the entity of the intraoperative EMG discharges and the postoperative
      facial and trigeminal function. Intraoperative EMG monitoring can be useful
      during the period of learning as a means of identifying the different nerves in
      the cisternal tract.

PMID- 15583465
TI  - Recovery of pain control by intensive reprogramming after loss of benefit from
      motor cortex stimulation for neuropathic pain.
AB  - INTRODUCTION: Motor cortex stimulation (MCS) may serve as an adjunct in managing
      neuropathic pain after other conservative and interventional methods have failed.
      However, the magnitude and duration of the benefit are highly variable, with a
      significant percentage of patients losing pain relief over time. We investigated
      whether intensive reprogramming could recapture the beneficial effects of MCS.
      METHODS: Six patients who had previously undergone MCS implantation for
      neuropathic pain but had lost benefit were brought back for 1-5 days of intensive
      reprogramming. Four patients were evaluated as inpatients while the others were
      seen as outpatients during multiple visits over several days. Several hours a day
      were spent with each patient. Patients completed visual analog scale (VAS)
      ratings at intervals throughout the reprogramming period to judge effectiveness
      of stimulation. Pre- and postadjustment VAS were compared using a paired t test.
      RESULTS: The patients' average age was 50 years (range 26-71). The diagnoses were
      trigeminal neuropathic pain (2 patients), complex regional pain syndrome I (2),
      phantom limb pain (1) and poststroke pain (1). The mean duration of pain was 6
      years. The MCS benefit had initially lasted for a mean of 7.16 months (range 2-18
      months). After reprogramming, 5 of 6 patients experienced improvement in pain.
      Average VAS scores decreased from 7.44 to 2.28 (p < 0.001) in those patients who
      responded to reprogramming. The average stimulation parameters in these patients
      were 5 V amplitude (range 1.7-10), 313 micros pulse width (range 240-390) and
      frequency of 84 Hz (range 55-130). Three patients experienced seizures during
      reprogramming. The mean seizure threshold was 8.9 V. No patient experienced
      seizures at their therapeutic settings. Pain control has been maintained after
      discharge. CONCLUSION: Intensive reprogramming can recapture the benefit of MCS
      in patients who have lost pain control. The use of broad dipoles using two
      contacts rather than one contact of the 1 x 4 electrode array improved the
      ability to recapture beneficial stimulation. There is a significant risk of
      seizures during aggressive reprogramming.

PMID- 15583466
TI  - Is serum ferritin an additional cardiovascular risk factor for all postmenopausal
      women?
AB  - BACKGROUND: Most of the studies on cardiovascular disease (CVD) risk factors in
      menopause have focused on serum lipid(lipoprotein) abnormalities and were
      conducted in populations which were not well controlled for several important
      influential factors. METHODS: Two homogenous groups of 30 apparently healthy
      Caucasian premenopausal women and 3-5 years postmenopausal women who were
      nonobese, nonsmoking and not using estrogen were compared in a well-controlled
      cross-sectional design. Fasting serum ferritin and plasma total homocysteine
      (tHcy) were evaluated concomitantly to classical serum lipid(lipoprotein) risk
      factors. Relationships between risk factors and the influence of other
      contributing variables such as diet and body weight were also examined. RESULTS:
      Serum total cholesterol (p < 0.01), low-density lipoproteins (LDL; p < 0.05) and
      triglycerides (p < 0.05) of postmenopausal women were greater than that of their
      menstruating counterparts, even though they ate a CVD-preventive diet, had
      similar body weight and body fat distribution. Their serum ferritin was almost 3
      fold greater (p < 0.0001) but was still within normal limits, except for the
      38.5% of postmenopausal women who exhibited values above the 80 mug/l limit that
      has been associated with sharp increases in the rate of heart disease in either
      gender. Serum ferritin was low in one third of the postmenopausal group (as low
      as in the premenopausal control group, whose dietary iron intake was slightly
      below the nutritional recommendation). The mean plasma tHcy of the postmenopausal
      group was almost twice as elevated (p < 0.0001). Both ferritin and tHcy were
      found to be linked to serum cholesterol. The correlation between tHcy and
      triglycerides was also significant. CONCLUSION: Early menopause is not associated
      with blood iron overload and CVD risk factor in an important proportion of women.

PMID- 15583467
TI  - Vegetable, fruit, and cereal intake and risk of idiopathic pulmonary fibrosis in
      Japan.
AB  - AIMS: There has been little interest in the role of nutrition in prevention of
      idiopathic pulmonary fibrosis (IPF). We investigated the relationship between
      dietary intake of vegetables, fruit, cereals, antioxidants, and fiber and the
      risk of IPF in Japan. METHODS: Included were 104 cases aged 40 years or over who
      were within 2 years of the diagnosis in accordance with the most recent criteria.
      Controls aged 40 years or over comprised 56 hospitalized patients diagnosed as
      having acute bacterial pneumonia and 4 outpatients with common cold. Information
      on dietary factors was collected using a validated self-administered diet history
      questionnaire. Adjustment was made for age, sex, region, pack-years of smoking,
      employment status, occupational exposure, saturated fatty acid intake, and body
      mass index. RESULTS: Consumption of fruit in the second and third quartiles was
      associated with a statistically significant reduced risk of IPF. Although not
      statistically significant, a beneficial association between soluble fiber intake
      and IPF was found. No statistically significant dose-response relationship was
      observed between intake of green and yellow vegetables, other vegetables,
      cereals, beta-carotene, vitamins C and E, or insoluble fiber and the risk of IPF.
      CONCLUSION: Our findings suggest that fruit intake may confer protection against
      the development of IPF.

PMID- 15583468
TI  - Regulatory effect of sense line diet on cholesterol and body weight in mice fed a
      high-fat diet.
AB  - BACKGROUND/AIMS: Sense line diet (SLD) is a newly developed dietary functional
      food that is composed of a lot of herbs. The function of SLD is to help control
      weight. Although it is reported that each herb has effects on lipid metabolism
      and obesity, these effects are not the same as SLD. The aim of this study was
      therefore to investigate whether SLD combined with high fat (HF) diet can
      influence body weight and fat accumulation. METHODS: An experiment was conducted
      with 40 C57BL/6J mice with an initial body weight of about 16 g. Body weight was
      recorded every week, plasma levels of triglyceride, low-density lipoprotein (LDL)
      cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed at the
      end of the study. RESULTS: Weight increases in the 10 or 20% SLD group were
      significantly less than in the HF diet group (p < 0.05). Plasma triglyceride and
      LDL cholesterol levels were decreased by 52.1 and 34.2% in the 10% SLD group and
      15.4 and 15.4% in the 20% SLD group, respectively, compared to the high-fat diet
      group. HDL cholesterol level was increased by 7.8% in the 10% SLD and by 54.9% in
      the 20% SLD group. CONCLUSIONS: Our findings indicate that SLD may be beneficial
      in the regulation of high-fat-diet-induced blood circulatory disorders as well as
      overweight.

PMID- 15583469
TI  - Metabolic and hematological effects of dietary supplementation with arginine on
      rats bearing ascitic Walker 256 tumor.
AB  - The notion of using supplementary quantities of arginine for nutritional support
      in patients with cancer has been evaluated not only as supplement intake of
      nitrogen substrate but also for its immunopharmacological effects capable of
      improving the patient's prognosis. The aim of the present study is to evaluate
      the effects of dietary supplementation with arginine on metastatic dissemination,
      amino acid metabolism, hematological functions of rats with Walker 256 ascitic
      tumor. Animals were inoculated intraperitoneally with approximately 4 million
      cells. Nutritional solutions containing 4 or 6% arginine or just a control diet
      without added arginine, were administered to the animals via esophagic gavages.
      The rate of metastasis was lower in animals supplemented with arginine at 4 and
      6%. Amino acid metabolism was stimulated in tumor-bearing animals after receiving
      4 or 6% arginine, demonstrated by significant increase of arginine, ornithine,
      citrulline, proline and histidine levels in the blood (p < or = 0.001) when
      compared to the control diet group. Anemia was less severe in tumor-bearing
      animals that received arginine supplementation. The findings suggest that
      arginine supplementation at 6% may have a beneficial effect on to the host,
      besides its pharmacological action.

PMID- 15583470
TI  - Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 as diagnostic
      markers of growth hormone deficiency in infancy.
AB  - BACKGROUND: The diagnosis of growth hormone deficiency (GHD) in infancy is
      difficult, and no specific cutoff value during GH provocative testing is
      recommended in early life. METHODS: Serum insulin-like growth factor I (IGF-I)
      and serum IGF-binding protein 3 (IGFBP-3) levels were evaluated as diagnostic
      markers of GHD. Measurements of IGF-I and IGFBP-3 during the 1st year of life
      were analyzed in 11 patients clinically suspected of having GHD (neonatal
      hypoglycemia, micropenis, or evidence of other pituitary hormone deficiencies),
      in whom the diagnosis was later verified. A prospective cohort of 51 healthy
      infants served as controls. RESULTS: The sensitivity of IGF-I as a diagnostic
      marker of GHD was 90% (10 out of 11 patients) with a cutoff value of -2 standard
      deviations (SD), and the sensitivity of IGFBP-3 measurements was 81% (9 out of 11
      patients) with a cutoff value below -2 SD. One patient had serial measurements
      before initiation of GH treatment where the IGF-I was fluctuating (3 of 6
      slightly above -2 SD), whereas all IGFBP-3 measurements were below -2 SD.
      CONCLUSIONS: The IGF-I had a high sensitivity in detecting infants with GHD. The
      combination of IGF-I and IGFBP-3 increased the diagnostic sensitivity. We
      speculate that assessment of IGF-I and IGFBP-3 may add diagnostic value in
      infants suspected of having GHD and furthermore that values below -2 SD are
      highly suggestive of GHD.

PMID- 15583471
TI  - Effect of estrogen on melanocortin-3 receptor mRNA expression in mouse pituitary
      glands in vivo and in vitro.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) stimulates prolactin (PRL)
      release and mammotrope proliferation in mouse anterior pituitary glands. The
      present study investigated the regulation of melanocortin-3 receptor (MC3-R) mRNA
      levels in mice using semi-quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis. Relative MC3-R mRNA levels in the anterior lobes of
      female mice increased between 20 and 45 days of age, and a significant difference
      in MC3-R mRNA expression between sexes was seen at 45 days. Ovariectomy decreased
      MC3-R mRNA expression in the female anterior lobes, and estradiol-17beta (E(2))
      treatment increased MC3-R mRNA levels in ovariectomized mouse anterior lobes and
      cultured anterior pituitary cells. E(2) treatment increased proopiomelanocortin
      (POMC) mRNA levels in ovariectomized mouse neurointermediate lobes and cultured
      neurointermediate pituitary cells. On the other hand, E(2) treatment did not
      affect POMC mRNA expression in mouse anterior lobes or cultured anterior
      pituitary cells. These results suggest that alpha-MSH directly stimulates PRL
      release and mammotrope proliferation through MC3-Rs expressed in mammotropes,
      while estrogen stimulates MC3-R gene transcription in the anterior pituitary
      cells and POMC gene transcription in the intermediate lobes. In lactating mice,
      POMC mRNA levels in the neurointermediate lobes were elevated compared with in
      non-lactating mice. The present study suggests that alpha-MSH is involved in
      augmented PRL secretion by estrogen and during lactation.

PMID- 15583472
TI  - Changes in gamma-aminobutyric acid tone and extracellular serotonin in the dorsal
      raphe nucleus over the rat estrous cycle.
AB  - Gender differences in serotonin (5-HT) metabolism, synthesis, and release suggest
      that the gonadal steroids estrogen (E) and progesterone (P) influence 5-HT
      neurotransmission. Based on the effects of ovarian steroids in forebrain sites,
      this might involve changes in the strength of GABA afferent tone in the dorsal
      raphe nucleus (DRN). To test this hypothesis, the present study used in vivo
      microdialysis to measure basal extracellular 5-HT in the rat DRN across the
      estrous cycle and changes in 5-HT in response to the GABA(A) receptor antagonists
      bicuculline (50 microM) and picrotoxin (50 microM). During proestrus and estrus,
      baseline 5-HT levels were significantly higher compared to ovariectomized (OVX)
      rats. Mean baseline levels across experiments were 8.4 +/- 1.3 pg/ 30 microl in
      proestrus, 5.2 +/- 0.8 pg/30 mul in estrus, and 3.1 +/- 0.5 pg/30 microl in the
      DRN of OVX rats. Bicuculline and picrotoxin produced significantly greater
      increases in 5-HT during proestrus compared to estrus. Moreover, in the DRN of
      OVX rats, bicuculline and picrotoxin produced negligible increases in 5-HT. These
      data provide evidence of decreased 5-HT efflux and GABA tone in the rat DRN
      associated with low circulating E and P.

PMID- 15583473
TI  - Isolation and characterization of the follicle-stimulating hormone beta subunit
      gene and 5' flanking region of the Chinook salmon.
AB  - In this study we have isolated the follicle-stimulating hormone beta subunit gene
      from the Chinook salmon (csFSHbeta). This gene encodes for a protein that is
      highly similar to those isolated from other salmonids and shares all of the
      structural constraints seen in mammalian gonadotropins, including twelve
      conserved cysteines and a putative N-linked glycosylation site. The organization
      of the gene follows the conserved pattern regarding the numbers and positions of
      the introns, although the csFSHbeta gene contains a particularly large 6.2-kb
      first intron due to the inclusion of several transposon-like elements. Isolation
      of 1.2 kb of the 5' flanking region of the csFSHbeta gene and subsequent analysis
      in silico have revealed a number of putative elements which appear highly
      conserved in teleost FSHbeta gene promoters and are thus likely involved in basal
      and hormone-induced transcriptional regulation. The functionality of this 1.2-kb
      fragment in driving expression of a reporter gene and its response to GnRH was
      shown in gonadotropes, while the overexpression of AP-1 factors, Sf-1, estrogen
      receptor or Smad1 revealed that the promoter is responsive to these transcription
      factors. Our current study has opened the way for future analysis to verify the
      role of these factors in mediating hormonally induced transcription of this gene.

PMID- 15583474
TI  - Decreased hypothalamic and adrenal angiotensin II receptor expression and
      adrenomedullary catecholamines in transgenic mice with impaired glucocorticoid
      receptor function.
AB  - In transgenic mice expressing an antisense mRNA against the glucocorticoid
      receptor (GR), which partially blocks GR expression, impaired glucocorticoid
      feedback efficacy is accompanied by reduced hypothalamic corticotropin-releasing
      hormone (CRH) and vasopressin (AVP) activity and reduced peripheral sympathetic
      tone, indications of a shift in the balance of hypothalamic CRH and sympathetic
      regulation. As angiotensin II (Ang II) regulates CRH, AVP and sympathetic
      activity, we studied the expression of Ang II receptors in the hypothalamus and
      adrenal gland of GR transgenic and wild-type mice, adrenal catecholamines and
      mRNA for their rate-limiting enzyme, tyrosine hydroxylase (TH). We found that
      transgenic mice expressed significantly less numbers of Ang II AT(1) receptors in
      the hypothalamic paraventricular nucleus and median eminence, lower numbers of
      AT(2) receptors in supraoptic and paraventricular nuclei and lower numbers of
      AT(2) receptors in the adrenal medulla when compared with wild-type controls. The
      expression of TH mRNA and the concentration of adrenomedullary epinephrine and
      norepinephrine were also lower in transgenic mice when compared with wild-type
      controls. Decreased hypothalamic and adrenal Ang II receptor stimulation as a
      result of decreased GR expression may explain the decreased hypothalamic CRH and
      AVP and decreased adrenomedullary and sympathetic activities in this model.

PMID- 15583475
TI  - Hypothalamo-pituitary-adrenal axis-regulated stress response and negative
      feedback sensitivity is altered by prenatal morphine exposure in adult female
      rats.
AB  - It has been shown that adult female rats react to stressors more intensely than
      adult male rats. Our previous work demonstrated that the adrenocorticotropic
      hormone (ACTH) but not corticosterone (CORT) response to stress is altered by
      prenatal morphine exposure in adult male rats. Response of the hypothalamo
      pituitary-adrenal (HPA) axis to stress is known to be sex specific and dependent
      on the hormonal fluctuation of the estrous cycle. Therefore, the present study
      examined the effect of prenatal morphine exposure on the levels of ACTH and CORT
      before and after restraint stress in adult female rats. Experiment 1 tested ACTH
      and CORT plasma levels before and after restraint stress in prenatally morphine-
      and saline-exposed, adult diestrus and proestrus female rats. Prenatal morphine
      exposure suppressed the restraint stress-induced ACTH levels in both diestrus and
      proestrus females, but did not have any effects on the basal or stress-induced
      CORT levels. Experiment 2 examined the sensitivity of negative feedback using the
      dexamethasone (DEX) (0.001, 0.01, 0.1 and 1.0 mg/kg) suppression test in adult,
      prenatally morphine- and saline-exposed female rats. In saline-exposed, proestrus
      but not diestrus females, all doses of DEX were effective in suppressing the
      restraint stress-induced increase in CORT levels. In both diestrus and proestrus,
      morphine-exposed females, only the two highest doses of DEX (0.1 and 1.0 mg/kg)
      were successfully suppressing the stress-induced CORT levels. The stress-induced
      increase in the ACTH level was suppressed only by the highest dose of DEX (1.0
      mg/kg) in both saline- and morphine-exposed, diestrus and proestrus females.
      Thus, the present study demonstrates that prenatal morphine exposure alters the
      HPA axis-regulated stress response and the sensitivity of negative feedback that
      are affected by the fluctuation of ovarian hormones.

PMID- 15583476
TI  - Expression analysis of the SG-SSPN complex in smooth muscle and endothelial cells
      of human umbilical cord vessels.
AB  - Recently, participation of the sarcoglycan (SG)-sarcospan (SSPN) complex in the
      development of cardiomyopathy in patients with limb-girdle muscular dystrophy has
      been shown, and presence of the complex in smooth muscle may be important for the
      contraction/dilation process of vessels. However, there are few studies
      determining the SG-SSPN complex in vascular smooth muscle and endothelial cells
      of vessels. In this study, we analyzed by reverse transcriptase-polymerase chain
      reaction and immunofluorescence the expression of different components of the
      complex in vein/artery smooth muscle and endothelial cells of the human umbilical
      cord. By RNA analysis, we observed expression of alpha-, beta-, gamma-, delta-,
      epsilon-SG, and SSPN in smooth muscle cells. In endothelial cells, RNA expression
      was restricted to beta-, delta-, epsilon-SG, and SSPN. At protein level, we
      observed in smooth muscle the presence of beta-, delta-, epsilon-SG, and SSPN. In
      endothelial cells, immunostaining only evidenced the presence of epsilon-SG and
      SSPN. However, colocalization of SGs and SSPN with dystrophin and utrophin was
      noted. These results, interestingly, suggest that the SG-SSPN complex may either
      form with dystrophin or utrophin in smooth muscle cells, and with utrophin in
      endothelial cells. Additionally, we also observed in some smooth muscle regions
      the colocalization of the SG-SSPN complex with caveolin, with colocalization
      being more pronounced between epsilon-SG-SSPN and caveolin in endothelial cells.

PMID- 15583477
TI  - Alteration of redox state of human serum albumin before and after hemodialysis.
AB  - BACKGROUND: Persistent hypoalbuminemia is a predictor of death in long-term
      maintenance hemodialysis patients, although cardiovascular diseases remain the
      leading cause of death. A decreased serum antioxidant activity in maintenance
      hemodialysis patients may contribute to increased oxidative damage, and may be
      associated with accelerated atherosclerotic changes. METHODS: The aim of this
      study was to examine the redox state of human serum albumin in maintenance
      hemodialysis patients by high-performance liquid chromatography (HPLC) using a
      fluorescence detector. RESULTS: HPLC of human serum albumin on a Shodex-Asahipak
      ES-502N column at pH 4.85 showed a clear resolution of human mercaptalbumin (HMA)
      and nonmercaptalbumin (HNA), which are the reduced and oxidized forms of human
      serum albumin, respectively. The mean +/- SD percentage of the HMA fraction of
      human serum albumin was significantly lower in maintenance hemodialysis patients
      than in age-matched normal subjects. The percentage of HMA increased 3-5 h after
      starting the hemodialysis and then decreased to subnormal levels. CONCLUSION:
      This suggests that serum albumin may be a major extracellular antioxidant in
      maintenance hemodialysis patients, and that hemodialysis may rescue serum albumin
      reduction by inducing intermolecular sulfhydryl-disulfide exchange reaction.

PMID- 15583478
TI  - Cytokine adsorptive property of various adsorbents in immunoadsorption columns
      and a newly developed adsorbent: an in vitro study.
AB  - BACKGROUND/AIMS: Cytokines play important roles in the pathophysiology of
      systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, some
      effective measures to remove cytokines from the bloodstream could be effective in
      the treatment of SIRS and sepsis. The aim of this study was to evaluate the
      cytokine adsorptive property of various adsorbents for the purpose of the
      development of new selective cytokine adsorption columns. METHODS: The cytokine
      adsorptive property of adsorbent in a CF-X column, which consists of cellulose
      beads cross-linked with hexamethylene-di-isocyanate, was compared with those of
      various adsorbents in currently available immunoadsorption columns, such as
      Immusorba TR, Immusorba PH, Selesorb, and Lixelle, in vitro batchwise test using
      patients' plasma. A newly developed adsorbent, MPCF-X, which was modified by
      coating the surface of the adsorbent in CF-X with 2-methacryloyloxyethyl
      phosphorylcholine (MPC), was also tested for its cytokine adsorptive property.
      RESULTS: The adsorbent in CF-X showed a significantly higher adsorption rate for
      TNF-alpha, interleukin (IL)-6 and IL-10 compared with other adsorbents (p <
      0.05). Adsorbent in Lixelle showed good affinity to TNF-alpha and IL-8.
      Especially, the adsorbent in CF-X almost completely removed TNF-alpha, whereas it
      also had considerable affinity to normal IgG. MPCF-X showed decreased affinity to
      IgG with considerable adsorptive properties to cytokines. CONCLUSION: Selective
      cytokine adsorption columns could be developed with improvement of currently
      available adsorbents. Such a new selective cytokine adsorption column could be
      clinically applied for the treatment of SIRS/sepsis.

PMID- 15583479
TI  - Sudden death in Prader-Willi syndrome during growth hormone therapy.
AB  - We describe a child with Prader-Willi syndrome (PWS) aged 3 years and 11 months
      who suddenly died 7 months after the initiation of GH therapy. The child never
      showed respiratory problems, but suffered from severe obesity. This case raises
      the question about the association between sudden death in children with PWS
      (with or without respiratory problems) and GH therapy, as already suspected in
      the recent past. We suggest that further epidemiological studies are required in
      order to determine more accurately the frequency of this causal connection and
      better understand its pathogenesis.

PMID- 15583481
TI  - Editorial - Beyond PBL.

PMID- 15583480
TI  - Effects of HMG-CoA reductase inhibition on hepatic expression of key cholesterol
      regulatory enzymes and receptors in nephrotic syndrome.
AB  - BACKGROUND: Hypercholesterolemia is one of the major manifestations of nephrotic
      syndrome. We have previously shown that nephrotic hypercholesterolemia is
      associated with and, in part, due to dysregulation of hepatic HMG-CoA reductase,
      acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol 7alpha-hydroxylase,
      as well as lecithin:cholesterol acyltransferase (LCAT), low-density lipoprotein
      (LDL) receptor and high-density lipoprotein (HDL) receptor deficiencies. This
      study was carried out to discern the effect of inhibition of HMG-CoA reductase on
      expression of the key enzymes and receptors involved in cholesterol metabolism in
      the liver. METHODS: Rats with puromycin-induced nephrotic syndrome were treated
      with either a statin (rosuvastatin 20 mg/kg/day) or placebo for 2 weeks. Placebo
      treated normal rats served as controls. Gene expression, protein abundance and/or
      activities of relevant receptors and enzymes were quantified. RESULTS: The
      untreated nephrotic rats showed heavy proteinuria, hypoalbuminemia,
      hypercholesterolemia, elevated total cholesterol:HDL cholesterol ratio and normal
      creatinine clearance. This was associated with severe reductions in hepatic LDL
      receptor, hepatic HDL receptor and plasma LCAT concentration, marked upregulation
      of hepatic ACAT, and unchanged cholesterol 7alpha-hydroxylase (rate-limiting step
      in cholesterol catabolism). Statin administration for 2 weeks ameliorated hepatic
      LDL receptor and HDL receptor deficiencies and significantly lowered plasma
      cholesterol, LDL cholesterol, total cholesterol:HDL cholesterol ratio and
      proteinuria. CONCLUSIONS: HMG-CoA reductase inhibition improved hepatic LDL and
      HDL receptor deficiencies, and ameliorated the associated hyperlipidemia in the
      nephrotic rats.

PMID- 15583482
TI  - Requesting organ donation: the case of self-efficacy--effects of the European
      Donor Hospital Education Programme (EDHEP).
AB  - One of the major reasons for the shortage of donor organs is the high number of
      refusals by relatives. Studies have shown that the quality of communication with
      bereaved relatives influences whether to object or agree to organ and/or tissue
      donation. Breaking news of brain stem death, approaching relatives for permission
      to donate organs while also appropriately managing emotional reactions of
      relatives are complex tasks, which require knowledge of the domains as well as
      adequate skills to communicate information and understanding. In this study the
      effect of the European Donor Hospital Education Programme (EDHEP) on the self
      efficacy of Intensive Care staff is evaluated. Self-efficacy scores significantly
      improved after attending EDHEP; an effect that was maintained at six month follow
      up. EDHEP participants with high baseline scores on self-efficacy, maintained the
      increase at follow-up. EDHEP participants with low baseline scores on self
      efficacy showed the greatest increase at the post-test. Increases in self
      efficacy were significantly related to decreases in the perceived difficulty of
      requesting. Experience had a significant effect on both self-efficacy beliefs and
      perceived difficulty of requesting donation. As self-efficacy beliefs are
      perceived as better predictors for future behaviour than prior attainments, the
      results call for further research in this domain. The data indicate that training
      programmes should be tailored not only to working circumstances of participants,
      but should also take levels of experience and self-efficacy into account. Further
      study is necessary and the best way to proceed is to relate the outcomes of this
      study to behavioural outcomes.

PMID- 15583483
TI  - Sources of measurement error in an ECG examination: implications for performance
      based assessments.
AB  - OBJECTIVE: To assess the sources of measurement error in an electrocardiogram
      (ECG) interpretation examination given in a third-year internal medicine
      clerkship. DESIGN: Three successive generalizability studies were conducted. (1)
      Multiple faculty rated student responses to a previously administered exam. (2)
      The rating criteria were revised and study 1 was repeated. (3) The examination
      was converted into an extended matching format including multiple cases with the
      same underlying cardiac problem. RESULTS: The discrepancies among raters (main
      effects and interactions) were dwarfed by the error associated with case
      specificity. The largest source of the differences among raters was in rating
      student errors of commission rather than student errors of omission. Revisions in
      the rating criteria may have helped increase inter-rater reliability slightly
      however, due to case specificity, it had little impact on the overall reliability
      of the exam. The third study indicated the majority of the variability in student
      performance across cases was in performance across cases within the same type of
      cardiac problem rather than between different types of cardiac problems.
      CONCLUSIONS: Case specificity was the overwhelming source of measurement error.
      The variation among cases came mainly from discrepancies in performance between
      examples of the same cardiac problem rather than from differences in performance
      across different types of cardiac problems. This suggests it is necessary to
      include a large number of cases even if the goal is to assess performance on only
      a few types of cardiac problems.

PMID- 15583484
TI  - Student USMLE step 1 preparation and performance.
AB  - OBJECTIVES: Many medical students take commercial preparation courses to prepare
      for the USMLE Step 1. This investigation examined the relationships among Step 1
      performance, preparation method, and academic achievement in medical school.
      METHOD: A survey was conducted on 148 junior students at a medical school in July
      2000 regarding their preparation methods for Step 1. Additional data was
      collected on student Step 1 scores, attendance record on preparation courses, and
      course grades in medical school. RESULTS: One hundred students (68%) responded to
      the survey including 32 preparation course participants. Course participants had
      significantly lower Step 1 scores and second-year GPAs than those of the non
      participants (p < 0.05). However, the effect of preparation method was not
      significant by using ANCOVA when the second-year GPA was used as a covariate (p =
      0.71). CONCLUSION: Performance on Step 1 is related to academic performance in
      medical school and not the type of preparation methods.

PMID- 15583485
TI  - Students' assessment of problems in a problem-based learning pharmacology course.
AB  - Problem-based learning has been widely employed in Medical Education. One of its
      main components is that students construct their knowledge working with problems.
      Therefore, in literature special attention has been given to the design of
      problems, while assessment has not received the same emphasis. To assess problems
      implies determining to which extent the resulting work fulfills the purposes that
      the designers of problems had planned, based on theoretical rationale. This study
      was developed to determine: if working with the problems allowed the students to
      carry out the expected learning activities; if the conditions in which they
      worked were suitable and if the problems were correctly structured. Participants
      were second-year medical students, enrolled in a problem-based learning
      pharmacology course. They were asked to assess each problem they used, by means
      of a questionnaire. The results suggest that when students worked with the
      problems they carried out activities related to elaboration of knowledge and
      activation of prior knowledge. They reported to have doubts after working with
      problems; this can probably be attributed to deficiencies in the students' prior
      knowledge. Furthermore, the type of problem in which students had low preference
      were those where they have to analyze tables and charts taken from
      pharmacological experiment reports; neither the time available to gather the
      information and to prepare the study issues was sufficient, nor was to study for
      other subjects. The information produced by assessment is useful for the
      designers of problems and as feedback to the educational process. The students'
      participation in the evaluation phase is a way to keep the congruence with a
      student-centered approach.

PMID- 15583486
TI  - Demonstration of portfolios to assess competency of residents.
AB  - Residency educators are identifying approaches to measure resident competence.
      Portfolios are well suited since they require work already completed as part of
      patient care where competency must be demonstrated. This paper describes
      assessment of the reliability and validity of portfolios in a psychiatry
      residency program. This was a cross-sectional study across 4years of residency
      education. Using guidelines, 18 residents assembled portfolios containing five
      entries chosen from 13 skills. Trained raters scored the portfolios. Residents
      and faculty were interviewed about their perceptions. Generalizability results
      indicated five entries and two raters were sufficient for relative decisions. Six
      entries or a third rater would be sufficient for absolute decisions. Portfolio
      scores tended to improve with years of training and correlated with psychiatric
      knowledge but not clinical performance. Residents and faculty identified benefits
      to assembling a portfolio. Portfolios incorporate tasks embedded in the residency
      to provide evidence of resident competency. The results support that the score is
      reliable and valid.

PMID- 15583487
TI  - Hilliard Jason, MD, EdD: a medical student turned educator.

PMID- 15583500
TI  - Systematic comparison of subjective and objective measures of quality of life at
      4-year follow-up subsequent to a first episode of psychosis.
AB  - There is enduring debate about the validity of subjective measures of quality of
      life derived from people with psychiatric disorders and particularly from those
      with psychosis. We evaluated patients with established psychosis 4 years after
      their first episode. We compared subjective and objective measures of quality of
      life and evaluated the influence of insight on the individual's interpretation of
      their quality of life. Subjective measures of quality of life were derived using
      the World Health Organization Quality of Life Scale-Brief Version, and objective
      measures of quality of life were derived using the Quality of Life Scale by
      Heinrichs et al. We measured Insight using the Insight Scale. There were robust
      correlations between subjective and objective assessments of quality of life.
      This was most marked for psychological symptoms. Self-report measures are valid
      and should form part of the overall assessment of quality of life among patients
      with psychotic disorders.

PMID- 15583501
TI  - A qualitative approach to identifying psychosocial issues faced by bipolar
      patients.
AB  - Many studies have examined factors influencing or associated with the outcome of
      bipolar disorder. However, little is known about bipolar patients' subjective
      experiences of their illness and the issues that are of significance to them. The
      use of a client-focused approach in identifying these issues is important for
      planning treatment and clinical medical management to address patients' specific
      needs. Focus group discussions and individual interviews were conducted with 18
      bipolar patients and transcribed verbatim. The data were then analyzed and
      interpreted according to the phenomenological approach to qualitative research.
      The data were interpreted in terms of how patients view themselves, their lives
      and community, and their future. Implications for treatment and future research
      are discussed.

PMID- 15583502
TI  - The association between spiritual and religious involvement and depressive
      symptoms in a Canadian population.
AB  - Data from a large epidemiologic survey were examined to determine the
      relationship of religious practice (worship service attendance), spiritual and
      religious self-perception, and importance (salience) to depressive symptoms. Data
      were obtained from 70,884 respondents older than 15 years from the Canadian
      National Population Health Survey (Wave II, 1996-1997). Logistic regression was
      used to examine the relationship of the religious/spiritual variables to
      depressive symptoms while controlling for demographic, social, and health
      variables. More frequent worship service attendees had significantly fewer
      depressive symptoms. In contrast, those who stated spiritual values or faith were
      important or perceived themselves to be spiritual/religious had higher levels of
      depressive symptoms, even after controlling for potential mediating and
      confounding factors. It is evident that spirituality/religion has an important
      effect on depressive symptoms, but this study underscores the complexity of this
      relationship. Longitudinal studies are needed to help elucidate mechanisms and
      the order and direction of effects.

PMID- 15583503
TI  - The course of PTSD, major depression, substance abuse, and somatization after a
      natural disaster.
AB  - Flood research has used a variety of methods, yielding inconsistent findings.
      Universal definitions of illness are paramount to the science of psychiatric
      epidemiology of disasters. St. Louis area survivors (N = 162) of the Great
      Midwestern Floods of 1993 received a structured diagnostic assessment at 4 and 16
      months postdisaster, with 88% follow-up. The purpose of the assessment was to
      examine predisaster and postdisaster rates of disorders and symptoms. Flood
      related posttraumatic stress disorder was diagnosed in 22% and 16% at index and
      follow-up, respectively. Comorbidity with major depression determined whether the
      posttraumatic stress disorder would have remitted by 1 year later. Nearly one
      half of the men in the sample had a pre-existing alcohol use disorder. Virtually
      no new substance abuse followed the floods, and hence, substance abuse did not
      develop in response to the disaster or as part of coping with its aftermath.
      Somatization disorder was not observed; new somatoform symptoms represented a
      fraction of postflood somatic complaints. Findings are inconsistent with causal
      attribution of floods in the etiology of alcohol abuse and somatization.
      Methodological differences may account for much of the apparent discrepancy of
      these findings, with recent reports of increased alcohol use and somatic symptoms
      observed after other disasters.

PMID- 15583504
TI  - Adolescent psychiatric inpatients' self-reported reasons for cutting themselves.
AB  - To ascertain (1) whether male and female adolescent (13-17 years old) psychiatric
      inpatients endorse comparable reasons for cutting themselves and (2) whether
      these reasons are correlated with selected psychosocial characteristics of the
      adolescents, self-reported depression, and hopelessness, the Self-Injury
      Motivation Scale II (SIMS-II), the Beck Depression Inventory-II, and the Beck
      Hopelessness Scale were administered to 19 (38%) male and 31 (62%) female
      adolescents who had cut themselves. Independent t tests found that none of the
      SIMS-II subscale scores was differentiated by sex, but the Beck Depression
      Inventory-II total score was significantly correlated with the SIMS-II total,
      Affect Modulation, Desolation, and Punitive Duality subscale scores. The results
      are discussed as indicating that male and female adolescent inpatients endorse
      comparable reasons for cutting themselves and that self-reported depression is
      positively associated with the number and intensity of different motivations for
      cutting oneself.

PMID- 15583505
TI  - Suicidal behavior and self-disclosure in adolescent psychiatric inpatients.
AB  - The inability to communicate feelings and thoughts to people close to oneself may
      be an important risk factor for suicidal behavior. This inability has been
      operationalized in the concept of self-disclosure. The purpose of this article
      was to evaluate the correlation of self-disclosure with suicidal behavior in
      adolescents. Eighty consecutive admissions to an adolescent psychiatric inpatient
      unit were evaluated. Thirty-four were suicide attempters, 18 were suicidal
      ideators, and 18 were nonsuicidal. Assessment measures included the Child Suicide
      Potential Scale, the Suicide Intent Scale, the Suicide Ideation Scale, and the
      Self-Disclosure Scale. The results show that low self-disclosure levels are
      associated with suicidal thinking, suicide attempts, and suicidal attitudes.
      Thus, low self-disclosure may well be a risk factor worthy of further evaluation
      in the attempt to understand adolescent suicidal behavior.

PMID- 15583506
TI  - Impact of a long asylum procedure on the prevalence of psychiatric disorders in
      Iraqi asylum seekers in The Netherlands.
AB  - Clinically, a long asylum procedure seems to be associated with psychiatric
      disorders. However, data on this issue are lacking. In a national community-based
      study, using random sampling, we compared two groups of Iraqi asylum seekers, who
      had resided less than 6 months (N = 143) and more than 2 years (N= 151),
      respectively, in The Netherlands. Respondents were interviewed with fully
      structured, culturally validated, translated questionnaires. Psychiatric (DSM-IV)
      disorders were measured with the Composite International Diagnostic Interview 2.1
      and evaluated in relation with premigration and postmigration adverse life
      events. Overall prevalence of psychiatric disorders was 42% in the first group
      and 66.2% in the second. The prevalence rates of anxiety, depressive, and
      somatoform disorders were significantly higher in the second group. Posttraumatic
      stress disorder was high in both groups but did not differ (p > .05). On logistic
      regression of all relevant risk factors, a long asylum procedure showed an odds
      ratio of 2.16 (confidence interval = 1.15-4.08) for psychopathology. The
      conclusion is that, indeed, the duration of the asylum procedure is an important
      risk factor for psychiatric problems. Both politicians and mental health workers
      should take note of this finding.

PMID- 15583507
TI  - Premigration exposure to political violence among independent immigrants and its
      association with emotional distress.
AB  - Although the distinction between independent immigrants and refugees has an
      impact on policy, services, and public opinion because it implies differences in
      resettlement needs, few recent studies have documented the validity of this
      assumption. In this population-based survey of recent migrants in Quebec (N =
      1871), immigration status (refugee, independent, or sponsored immigrant) is
      examined in relation to premigration exposure to political violence and refugees'
      emotional distress, assessed with the SCL-25. A higher percentage of refugees
      reported exposure to political violence in their homeland, but the percentages of
      exposed independent (48%) and sponsored (42%) immigrants were unexpectedly high.
      Emotional distress was significantly higher among Chinese respondents who had
      witnessed acts of violence and in subjects from Arab countries who reported
      persecution. These results suggest that service providers and policy makers
      should not assume that independent immigrants have not been exposed to political
      violence before their migration.

PMID- 15583508
TI  - Attachment styles and violence within couples.
AB  - This study examined whether an individual's attachment style and/or a couple's
      combination of attachment styles predicted violence within the marriage and
      explored whether other variables moderated the risk of violence. Measures of
      attachment style were administered to 41 discordant couples who presented to four
      different clinics. The couples' presenting complaints were not violence, and
      those who did report violence on questioning did not manifest severe violence,
      i.e., requiring shelters or legal intervention. Self-report measures of violence
      and marital satisfaction, including problem-solving communication, were also
      given. Using analysis of covariance and logistic regression, the relative
      contributions to strength of predicting being a victim of conjugal violence were
      calculated. An anxious attachment style was a significant predictor of females
      being victims of violence and of men not being victims. A dismissive style in men
      was predictive of men being victims when entered into the model with problem
      solving communication. The combination of anxiously attached females and
      dismissive males was a potent predictor of violence, and longer duration of
      marriage and poor problem-solving communication added power to the prediction.
      Marital interaction, which is influenced by couples' attachment styles and
      problem-solving communication, is a significant factor in marital partners
      experiencing physical violence. For couples with milder levels of violence, a
      more nuanced approach (compared with the legally based approach used for severe
      violence) seems indicated.

PMID- 15583509
TI  - A factor analysis of the Strauss and Carpenter revised outcome criteria scale: a
      validation of the French translation.
AB  - This article seeks to validate the French translation of the Strauss and
      Carpenter revised outcome criteria scale (SCOCS-R) through the study of its
      interrater reliability, its convergent validity, and its factor structure. Using
      a sample of 113 DSM-IV schizophrenic subjects, we assessed the interrater
      reliability of the SCOCS-R and its convergent validity with an already validated
      scale (Social and Occupational Functioning Assessment Scale). The factor
      structure of the SCOCS-R was assessed using a principal components analysis.
      Interrater reliability was excellent (ri > or = 0.88 for each of the individual
      items), and the convergent validity with the Social and Occupational Functioning
      Assessment Scale proved to be highly satisfactory (r = 0.89; p < .0001). Factor
      analyses yielded two factors corresponding to social functioning and professional
      functioning. These factors accounted for 78% of the variance of outcome. These
      results demonstrate the reliability and the validity of the French translation of
      the SCOCS-R. Moreover, the two dimensions yielded by our factor analysis add to
      the evidence of the multidimensional structure of outcome. This article supports
      the relevance of the SCOCS-R to assess the dimensions of outcome in schizophrenic
      subjects.

PMID- 15583510
TI  - Adjustment outcomes in Chinese patients following one-month recovery from severe
      acute respiratory syndrome in Hong Kong.
AB  - This study aimed to examine the short-term adjustment outcomes including
      distress, self-esteem, and quality of life among Chinese patients after 1-month
      recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to
      investigate the predictive abilities of a set of selected variables on the
      outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and
      184 community subjects completed self-administered questionnaires. In the General
      Health Questionnaire-28, 61% of the SARS survivors were identified as distressed
      cases under a conservative cutoff score of 6. Compared with the community sample,
      SARS survivors had significantly more distress and poor quality of life. Being a
      healthcare worker, severity of SARS symptoms, steroid dosage, and social support
      accounted for a portion of variances of different measures. Early psychiatric
      screening and intervention may be beneficial for the adjustment of SARS survivors
      after short-term recovery. Future research on the long-term impact of SARS is
      recommended.

PMID- 15583511
TI  - Psychiatric morbidity and quality of life in children with malignancies and their
      parents.
AB  - Recent improvements in prognosis necessitate considering the emotional responses
      of children with malignant diseases and of their parents. This prospective study
      assessed 20 children and adolescents and their 36 parents within 2 weeks of
      diagnosis and after 1 and 6 months. Fifty-three percent exhibited moderate to
      severe posttraumatic symptoms right after diagnosis that decreased significantly
      after 1 month. Children with high-risk disease reported the most severe symptoms.
      Unexpectedly, children with low-risk disease exhibited more severe symptoms than
      those with moderate risk. Depressive symptoms decreased significantly during the
      period, but anxiety symptoms did not. Moreover, quality of life did not change.
      Twenty percent of parents exhibited posttraumatic symptoms on initial evaluation.
      Mothers' symptoms did not change, but fathers' symptoms decreased with those of
      their children. Several procedures and experiences were identified as causes of
      traumatic stress responses.

PMID- 15583512
TI  - PTSD reactions and coping responses of East Coast and West Coast American
      Airlines flight attendants after September 11: a possible psychological contagion
      effect?
AB  - Psychological reactions and functional coping of East Coast and West Coast-based
      flight attendants were compared after the attacks on September 11. Demographics
      and standardized questionnaires were sent in June 2002 to approximately 26,000
      flight attendants. The 2,050 returned surveys were separated into East Coast
      based flight crews (513 from Boston, New York, and Washington, DC) and West Coast
      based flight crews (353 from Los Angeles and San Francisco). Despite demographic
      differences between the flight crews, most notably that the East Coast members
      were more than twice as likely to know someone who perished in the wake of
      September 11, there was no difference between them regarding probable PTSD (19.1%
      and 18.3%, respectively) or life functioning. We suggest that a psychological
      contagion effect occurred in this at-risk group of workers in the war on
      terrorism. Public health implications, including multicomponent treatment
      interventions, are suggested.

PMID- 15583513
TI  - Activation symptoms and discharge in elderly chronic schizophrenic inpatients.
AB  - Three hundred thirty-three elderly schizophrenic inpatients were rated on the
      Positive and Negative Syndrome Scale (PANSS), and those remaining in the hospital
      after 1 year (N = 267) were rated and followed for an additional year. Based on
      previous studies showing that aggressive episodes and hostile behavior predicted
      inability to discharge schizophrenics, we hypothesized that low discharge rates
      would be correlated with high baseline ratings on the activation factor of the
      PANSS (PANSS-AF), obtained by summing six items (hostility, poor impulse control,
      excitement, uncooperativeness, poor rapport, and tension). Baseline PANSS-AF
      scores were found to be inversely correlated with discharge rates, independent of
      ratings on other symptom dimensions. PANSS-AF scores were a better predictor of
      outcome than any individual PANSS item (e.g., hostility), and individual item
      scores did not add significantly to prediction of discharge. Attention to and
      development of treatments for activation symptoms, highly prevalent in
      schizophrenia but not included in our present diagnostic systems, may increase
      the chances of elderly inpatients with schizophrenia of moving to community
      settings.

PMID- 15583515
TI  - Ethical issues in psychiatric genetics.
AB  - As knowledge grows regarding the genetic bases of psychiatric disorders, a
      variety of ethical issues will need to be confronted. Current evidence suggests
      that the etiology of most psychiatric disorders rests on a combination of
      multiple genes and environmental factors. As tests for the genes involved become
      more easily available, pressures will arise to use them for prenatal testing,
      screening of children and adults, selection of potential adoptees, and pre
      marital screening. Common problems that will need to be addressed include popular
      misunderstanding of the consequences of possessing an affected allele, impact of
      knowledge of one's genetic make-up on one's sense of self, and the discriminatory
      use of genetic information to deny persons access to insurance and employment.
      Although most states have some legislation aimed at preventing discrimination,
      the laws' coverage is spotty and federal rules are lacking. Physicians may find
      that newly available genetic information creates new duties for them, including
      warning third parties who may share the patient's genetic endowment. And genetics
      research itself has raised questions about when to disclose information to
      subjects and their family members about the genes that are being studied, and how
      to define the subjects of the research when information is collected about family
      members other than the proband. Knowledge of these dilemmas is a first step to
      resolving them, something that the medical profession will need to attend to in
      the near-term. Neglect will lead others to set the rules that will control
      medical practice, including the practice of psychiatry, in the new world of
      genetic medicine.

PMID- 15583516
TI  - Psychiatry, moral worry, and the moral emotions.
AB  - There has been increased philosophical, psychological, and, more recently,
      psychiatric interest in the moral emotions, most specifically the emotions of
      guilt, shame, regret, and remorse. Interest in these emotions has not been in
      their role as symptoms of a particular mental illness, but in their presence in
      everyday life and in their importance in defining our character and our very
      humanity. Moral emotions are those emotions that arise in the context of life
      experiences and daily choices that bear upon our perceptions of the rightness or
      wrongness of particular actions or inactions. Human beings have a moral scanner
      that constantly provides both a cognitive judgment and a feeling tone of ease or
      unease in the moral evaluation of life's moment-to-moment activities. This paper
      discusses the intersection of psychiatry and the moral emotions, providing case
      examples and a review of empirical studies to illustrate the relevance of
      patients' concerns about their moral choices to psychiatric evaluation and
      practice.

PMID- 15583517
TI  - Ziprasidone: first year experience in a hospital setting.
AB  - BACKGROUND: The antipsychotic drug ziprasidone, FDA-approved and introduced in
      the United States in February 2001 for the treatment of schizophrenia, appears to
      have similar efficacy but better tolerability than older antipsychotics and
      requires further evaluation under clinical conditions. METHODS: We analyzed
      medical records of McLean Hospital inpatients treated with ziprasidone between
      March 2001 and February 2002, gathering data on DSM-IV diagnoses, presenting
      symptoms, dosing, concomitant psychotropic medications, clinical changes, adverse
      effects, and electrocardiographic (ECG) findings. RESULTS: Ziprasidone was given
      to 151 inpatients (3.4% of admissions; 108 women, 43 men), aged 37.5 +/- 11.4
      years, who presented with depression (n = 79), psychosis (n = 46), mania (n =
      18), bipolar mixed-states (n = 4), or other conditions (n = 4). Daily doses
      averaged 49.8 +/- 34.1 mg initially and 83.2 +/- 46.3 mg at discharge; the
      greatest dose increases during hospitalization (by a mean of 61%) were in
      patients with schizoaffective disorder (n = 46; 30% of cases). In 41 cases (27%),
      ziprasidone was the only antipsychotic at discharge; in 61 (40%) it was used with
      other antipsychotics. Ziprasidone was discontinued during hospitalization in 49
      cases (32.5%), due to lack of efficacy (n = 26; 17.2%), adverse effects (n = 13,
      8.6%), or reasons not stated (n = 10, 6.6%). Of 70 patients for whom ECG data
      were obtained during treatment with ziprasidone, 8 (11%) had QTc intervals > 450
      msec during treatment, but none of the 39 patients with ECGs both before and
      during ziprasidone treatment showed clinically meaningful increases in QTc
      intervals. Ziprasidone was discontinued in 4 patients (2.6%) due to concern about
      QTc intervals, but in no case was the QTc interval > or = 500 msec or associated
      with clinical cardiac toxicity. Improvements in CGI and GAF scores from admission
      to discharge were similar across diagnoses and unrelated to length of stay or
      ziprasidone dose. CONCLUSIONS: Ziprasidone was well tolerated by hospitalized
      patients with various major psychiatric disorders and may be of value in
      conditions other than schizophrenia.

PMID- 15583518
TI  - Psychological impact of the animal-human bond in disaster preparedness and
      response.
AB  - The authors present an overview of the impact of the animal-human bond on
      disaster management and highlight the need to further examine the relationship of
      animals and humans in disaster response. The human connection to animals
      influences compliance with individual and community evacuation plans. Search and
      rescue teams with canine units confront physical and emotional demands that
      affect both handler and animal. The culling of animal populations on a scale such
      as occurred during the recent foot-and-mouth epidemic in the United Kingdom
      affects every member of rural society. Livestock farmers and their families
      endure enormous emotional losses, and veterinarians and government officials who
      must implement these programs suffer as well. A familiarity with and
      understanding of these issues is important for psychiatrists and other mental
      health professionals who are involved in disaster preparedness and response.

PMID- 15583519
TI  - Duloxetine.

PMID- 15583520
TI  - Psychotherapy research:"horse race"versus process.

PMID- 15583521
TI  - Two cases from the forensic files.

PMID- 15583522
TI  - A visual guide to expected blood levels of long-acting injectable risperidone in
      clinical practice.
AB  - OBJECTIVE: Risperidone is the only second-generation (atypical) antipsychotic
      medication available in a long-acting injectable formulation. The mechanism of
      drug delivery and the pharmacokinetics of this medication are distinctively
      different from the first-generation injectable depot medications. Antipsychotic
      blood levels have been reported in carefully managed single-dose and multiple
      dose studies of long-acting risperidone. However, there have been no studies of
      blood levels produced by the variability in doses and schedules that may occur in
      clinical practice. Mathematical modeling allows for estimation of blood levels in
      a variety of clinical scenarios that have yet to be studied empirically. This
      paper presents mathematically modeled representations of antipsychotic blood
      levels in clinical situations with long-acting risperidone, with the goal of
      helping professionals, patients, and family members make informed decisions
      regarding treatment. METHODS: A model of single-dose pharmacokinetics was derived
      from a published, empirical single-dose study. The model was used to prepare
      graphs of expected multiple-dose schedules consistent with clinical situations,
      using empirically validated assumptions. RESULTS: The model was validated by
      comparison of the results of multiple-dose modeling with published empirical
      multi-dose data. Graphs of expected blood levels in several clinical situations
      are presented. Future empirical studies are required to fully validate these
      results. CONCLUSIONS: Mathematical models of antipsychotic blood levels in
      various common situations allow a better appreciation of the novel
      pharmacokinetics of long-acting injectable risperidone, which may lead to more
      informed decision-making.

PMID- 15583525
TI  - Dangerous drugs?

PMID- 15583526
TI  - Treatment of menopausal vasomotor symptoms.
AB  - The Women's Health Initiative finding that taking estrogen plus a progestin for
      more than five years increased the risk of cardiovascular disease and breast
      cancer left the safety of using estrogen to treat hot flashes open to question.
      How low a dose and how short a duration would be safe and effective are unknown.
      Lifestyle changes, antidepressants, alpha-2 agonists, anticonvulsants,
      phytoestrogens and other dietary supplements have been tried as alternatives to
      estrogen, with mixed results.

PMID- 15583527
TI  - Drugs for percutaneous coronary interventions.
AB  - Many combinations of anticoagulants and antiplatelet drugs have been used to
      treat patients undergoing a percutaneous coronary intervention (PCI). Among
      anticoagulants, enoxaparin has some theoretical advantages over unfractionated
      heparin, but in clinical trials no advantage in outcome has been demonstrated in
      PCI. Bivalirudin, a direct thrombin inhibitor, has been associated with a lower
      risk of bleeding than unfractionated heparin. Among antiplatelet drugs, use of
      clopidogrel plus aspirin has led to a reduction in cardiovascular events; all
      patients undergoing PCI should receive both. Addition of a GP IIb/IIIa inhibitor
      may lower mortality rates further, particularly in high-risk patients such as
      diabetics.

PMID- 15583528
TI  - How future tumor necrosis factor antagonists and other compounds will meet the
      remaining challenges in Crohn's disease.
AB  - The chimeric monoclonal antibody to tumor necrosis factor (TNF), infliximab, is
      an effective therapy for Crohn's disease. However, the formation of human anti
      chimeric antibodies to infliximab (immunogenicity) can lead to loss of efficacy
      as well as acute infusion reactions and delayed hypersensitivity reactions. The
      fully human monoclonal antibody adalimumab and the pegylated humanized monoclonal
      antibody fragment CDP870 are biologic therapies against TNF that might be
      effective for Crohn's disease and less immunogenic than infliximab. Other
      potential alternatives to infliximab for Crohn's disease include the humanized
      anti-adhesion molecule antibodies natalizumab and MLN-02, the humanized anti
      interleukin 12 antibody ABT-874, the humanized anti-interferon g antibody
      fontolizumab, the humanized anti-interleukin 6 receptor antibody MRA, and human
      recombinant granulocyte macrophage colony stimulating factor (sargramostim).
      Some, or all, of these therapies will likely represent important treatments for
      Crohn's disease in the future.

PMID- 15583529
TI  - Oral health in the elderly--what's missing?

PMID- 15583530
TI  - Cosmetically favorable scars using the upper blepharoplasty incision.

PMID- 15583531
TI  - The role of holmium:YAG laser in arthroscopy of the temporomandibular joint.

PMID- 15583532
TI  - Facial swelling and palatal ulceration in a diabetic patient.

PMID- 15583533
TI  - A prospective randomized crossover study of the preemptive analgesic effect of
      nitrous oxide in oral surgery.
AB  - OBJECTIVE: Preliminary animal data has shown that nitrous oxide has a preemptive
      analgesic effect on postoperative pain. Whether a similar effect occurs in humans
      is not established. In this prospective randomized crossover study, we
      investigated the effect of preincisional versus postincisional nitrous oxide on
      postoperative oral surgical pain.Study design The trial was a crossover study
      where 36 patients had each of their symmetrical impacted mandibular third molars
      randomly scheduled for removal in 2 sessions. Each of the 36 patients acted as
      his or her own control; one side of the jaw was allocated randomly to receive
      nitrous oxide preoperatively (pretreated side) and the other side postoperatively
      (posttreated side). The pretreated side received 50% nitrous oxide preoperatively
      for 20 minutes and 100% oxygen postoperatively for 20 minutes as placebo. The
      posttreated side received 100% oxygen preoperatively for 20 minutes and 50%
      nitrous oxide postoperatively for 20 minutes. The difference in postoperative
      pain between the pretreated and posttreated sides was assessed by 4 primary end
      points: pain intensity as measured by a 100-mm visual analog scale (VAS) hourly
      for 8 hours, time to first analgesic, total analgesic consumption during the
      first 48 hours, and a 5-point categorical patient global assessment scale
      (0=poor, 1=fair, 2=good, 3=very good, and 4=excellent). RESULTS: The VAS scores
      did not differ between the 2 sides at any time (P=.50): neither did the time to
      first analgesic (P=.8), amount of total analgesic consumption (P=.77), and
      patient's global assessment differ (P=.63). CONCLUSION: Our results do not
      support the preliminary animal data that nitrous oxide has a preemptive analgesic
      effect for postoperative pain. 50% nitrous oxide administered preoperatively for
      20 minutes has no preemptive analgesic effect on postextraction pain.

PMID- 15583534
TI  - Can infrared thermography be a diagnostic tool for arthralgia of the
      temporomandibular joint?
AB  - This paper presents a review of the use of infrared thermography in diagnosis of
      temporomandibular joint (TMJ) arthralgia. The question examined was whether the
      infrared thermography could be reliably used as a tool to diagnose arthralgia by
      objectively assessing the site of origin and the degree of irritation. Controlled
      studies were performed by using advanced thermographic devices to show both
      diagnostic validity and reliability of infrared thermography as a screening test
      for selecting healthy subjects from patients with unilateral TMJ arthralgia. The
      study revealed that thermography fails to meet the criteria of high level of
      evidence. Further studies are required to confirm these results in order to
      specify analysis of facial thermal patterns and to better understand the
      relationship between TMJ arthralgia and regional temperature changes. Until then
      infrared thermography cannot be recommended for routine use as a diagnostic
      technique to identify TMJ disorders.

PMID- 15583535
TI  - Comparative study of intra-articular irrigation and corticosteroid injection
      versus closed reduction with intermaxillary fixation for the management of
      mandibular condyle fractures.
AB  - OBJECTIVE: To evaluate the clinical outcome of a modified conservative treatment
      protocol involving intra-articular irrigation and corticosteroid injection into
      the superior joint compartment (SJC) of patients with fresh mandibular condyle
      fractures. Study design A total of 26 consecutive unilateral fresh condylar
      fractures in 26 patients were divided into the intra-articular irrigation (IR)
      group (14 patients, 14 joints) and the conventional conservative treatment (CC)
      group (12 patients, 12 joints). In the IR group, the SJCs of the fractured joints
      were irrigated with saline solution and injected dexamethazone sodium, followed
      by conventional rehabilitation. In the CC group, patients were treated by closed
      reduction with intermaxillary fixation (IMF) for 2 weeks, followed by
      conventional rehabilitation. Clinical outcome at 1 month, 3 months, 6 months, and
      1 year after injury was determined by clinical examination of jaw motion, joint
      pain, and occlusal changes. The posttreatment results were compared with the
      pretreatment baseline data. Between-group differences in clinical parameters were
      analyzed. RESULTS: There were significant between-group differences in the range
      of mandibular motion at 1 month and 3 months after injury (1 month, P=.0022; 3
      months, P=.0022). In the IR group, joint pain was well relieved from the early
      stage of treatment. Occlusal changes were found in 1 patient in the IR group and
      4 patients in the CC group at 1 year after injury. CONCLUSIONS: The modified
      treatment protocol involving intra-articular irrigation and corticosteroid
      injection into the SJC is a more effective and quick-acting modality than
      conventional closed reduction with IMF for functional recovery and control of
      clinical symptoms of patients with unilateral fresh condylar fractures.

PMID- 15583536
TI  - Recurrence of an ameloblastoma in an autogenous iliac bone graft.
AB  - A rare case of recurrence of an ameloblastoma in an iliac bone graft many years
      after the initial operation for a mandibular amelolastoma with evidence of soft
      tissue invasion is presented. A review of the literature disclosed only 11 cases
      of recurrence of ameloblastoma in bone grafts. In the case presented the initial
      operation was a hemimandibulectomy followed by autogenous iliac bone graft.
      Sixteen years after the surgery there was clinical and radiographic signs of
      recurrence. It was concluded that extensive resection including bone as well as
      adjacent soft tissues is critical because the recurrences seem to stem from the
      soft tissues, especially from the adjacent periosteum.

PMID- 15583537
TI  - Recurrent calcifying odontogenic cyst involving the maxillary sinus.
AB  - The calcifying odontogenic cyst is an uncommon lesion that occurs in both jaws,
      however involvement of the maxillary sinus is rare. The accepted mode of
      treatment is enucleation with curettage since it is generally believed that
      recurrence following such treatment is extremely rare. Of the reported cases of
      recurrent calcifying odontogenic cysts, none have involved the maxillary sinus.
      This report is of a large recurrent calcifying odontogenic cyst involving the
      maxillary sinus, eroding the orbital floor as well as anterior and medial walls
      of the maxillary sinus and displacing an impacted upper canine into the nasal
      cavity, in a 45-year-old male patient, 8 years after the initial enucleation.

PMID- 15583538
TI  - The role of oral microbial colonization in ventilator-associated pneumonia.
AB  - The present article reviews the association between microbial colonization of the
      oral cavity and the lungs in critically ill patients that develop ventilator
      associated pneumonia (VAP) in the intensive care unit (ICU) setting. The risk
      factors and microorganisms associated with VAP are presented. The role of oral
      colonization of VAP-associated pathogens (VAP-AP) in the development of VAP is
      examined. We explore the potential factors involved in oral colonization of VAP
      AP, which are atypical bacteria for the oral cavity. Strategies for the
      prevention or moderation of oral colonization of VAP-AP have had limited success.
      We need a deeper understanding of the pathophysiology of VAP in order to reduce
      the morbidity, mortality, and cost from this common complication in ICU medicine
      and surgery.

PMID- 15583539
TI  - Oral and serum IL-6 levels in oral lichen planus patients.
AB  - OBJECTIVE: The purpose of this study was to compare IL-6 levels in oral
      exfoliated mucosal cell samples and in serum in subjects with oral lichen planus
      versus controls. Study design Ten patients with ulcerative OLP, 10 with reticular
      OLP, and 10 control subjects were recruited at a University Oral Medicine Clinic.
      Using smear tissue culture brushes, oral samples were collected from lesional
      sites for OLP patients and from buccal mucosa for controls into vials with 300
      muL PBS. After centrifugation, the supernatants were aspirated for cytokine ELISA
      assay and protein assay. Venous blood was processed to serum for ELISA assay.
      Oral IL-6 was expressed as both pg/mL and pg/mug protein, and serum IL-6 was
      expressed as pg/mL. RESULTS: The mean oral IL-6 levels were higher in the
      ulcerative OLP group (11.19 +/- 5.34 pg/mL) than in the reticular OLP (1.05 +/-
      0.34 pg/mL) and control (0.52 +/- 0.29 pg/mL) groups. There were significant
      differences between ulcerative OLP and reticular OLP groups (P < .039), and
      between ulcerative OLP and control groups (P < .009). After the standardization
      of IL-6 concentration by protein, a significant difference in IL-6 concentration
      was shown only between the ulcerative OLP (0.0245 +/- 0.0121 pg/mug protein) and
      control (0.0023 +/- 0.0012 pg/mug protein) groups (P < .029). Similarly, the
      ulcerative OLP group showed a significantly higher serum IL-6 level than the
      control group (P < .021). CONCLUSION: Both oral and serum IL-6 levels were higher
      in patients with ulcerative OLP. An oral exfoliated cell technique may be a
      useful and sensitive method to measure IL-6 in patients with OLP as it provided
      results consistent with those found in peripheral blood.

PMID- 15583540
TI  - Initial diagnosis of anemia from sore mouth and improved classification of
      anemias by MCV and RDW in 30 patients.
AB  - Thirty patients with a wide range of sore mouth that led to the diagnosis of iron
      deficiency in 12 patients, pernicious anemia in 8 patients, combined deficiency
      of iron and vitamin B12 in 2 patients, and anemia of chronic disease in 8
      patients were investigated. The oral signs and symptoms included glossitis,
      glossodynia, angular cheilitis, recurrent oral ulcer, oral candidosis, diffuse
      erythematous mucositis, and pale oral mucosa. The values of hemoglobin in 30
      patients varied from normal to severe life-threatening levels, but none had
      developed generalized symptoms sufficiently advanced to arouse suspicions of
      anemia before they visited the Oral Medicine Clinic. The aim of this paper is to
      describe a retrospective study of 30 patients with oral changes as the initial
      manifestation of nutritional deficiency or anemia of chronic diseases. Improved
      diagnosis and classification of anemia based on the mean and heterogeneity of red
      cell size will be discussed.

PMID- 15583541
TI  - Enamel defects and Lyonization in focal dermal hypoplasia.
AB  - We report a pattern of enamel hypoplasia in focal dermal hypoplasia similar to
      that found in females with X-linked amelogenesis imperfecta. Three cases of focal
      dermal hypoplasia are described, with specific focus on the oral and dental
      features. In these cases the teeth all had vertical grooving with notching of the
      incisal or cuspal tips. Also recorded were blunt roots of taurodont form with
      open apices and missing teeth in 1 case. Oral papillomas were present in 2 cases.
      The pattern of enamel defects is attributed to Lyonization, which is consistent
      with the pattern of skin and bone lesions typically seen in focal dermal
      hypoplasia. This supports the proposal that focal dermal hypoplasia is X-linked.
      The authors conclude that the pattern of dental defects in focal dermal
      hypoplasia is consistent with Lyonization.

PMID- 15583542
TI  - Application of laser capture microdissection to phage display peptide library
      screening.
AB  - OBJECTIVE: When identifying important regulatory genes using methods such as
      phage display peptide library screening it is critical to select such peptides
      from cells and tissues in their native state. Here, we report a novel approach to
      screen tumors using phage display and laser capture microdissection (LCM). STUDY
      DESIGN: A phage peptide library was screened directly on fresh oral tumor tissue,
      such that specifically bound peptides were selected from fresh tumor cells in the
      native tissue state. Tissue processing conditions were modified to ensure the
      survival of the bacteriophage. RESULTS: Our results demonstrate that live phage
      peptide conjugates can be recovered from laser capture microdissected cells in a
      form suitable for additional cycles of amplification. CONCLUSION: Thus, LCM will
      be a valuable adjunct to phage display studies.

PMID- 15583543
TI  - Assessment of p63 expression in oral squamous cell carcinomas and dysplasias.
AB  - OBJECTIVES: p63, a p53 homologue, may be associated with tumorigenesis in
      epithelial tissues through its inhibition of p53 transactivation functions. We
      sought to determine the pattern and levels of p63 expression in oral dysplasias
      and carcinomas using standard immunohistochemical staining. We also assessed and
      compared expression of p53 and a cell proliferation marker in these lesions.
      STUDY DESIGN: This retrospective cross-sectional survey (n=67) included
      hyperkeratosis (10), mild dysplasia (9), moderate dysplasia (11), severe
      dysplasia/in situ carcinoma (10), squamous cell carcinoma (SCC) (22 [9 well
      differentiated, 7 moderately differentiated, 6 poor differentiated]), and normal
      mucosa (5). Serial sections were stained immunohistochemically with antibodies to
      p63 (4A4 recognizing all p63 isotypes), p53 (DO-7), and Ki-67 (MIB-1) proteins.
      In preinvasive lesions, both the percentage of positive cells and staining
      patterns (negative, basal, suprabasal) were assessed. In oral SCCs, the
      percentage of positive cells was assessed. Statistical analysis was done using
      the Tukey-Kramer multiple comparisons test. RESULTS: A suprabasal p63 staining
      pattern was evident in keratinocyte nuclei in the entire range of noninvasive
      lesions studied, including normal mucosa. Most nuclei in invasive SCCs stained
      positive. When all grades of dysplasia were combined, the percent of p63 positive
      cells was significantly greater than hyperkeratosis (P < .01), and well
      differentiated SCC (P < .001). Moderately differentiated SCC had statistically
      significant more positive cells than well-differentiated SSC (P < .01).
      Comparison of serial sections showed different p63 staining patterns compared to
      p53 or Ki-67 staining patterns. CONCLUSIONS: We conclude that p63 is expressed in
      oral carcinomas and dysplasias, as determined by immunohistochemical staining
      with a primary antibody to all isotypes. Neither staining pattern nor percentage
      of stained cells could be used to differentiate the lesions studied. The
      statistically significant differences found between some groups are not likely to
      be of diagnostic value. p63 is not coexpressed with p53 expression or Ki-67
      suggesting functional independence. When antibodies to the p63 isotypes become
      available, oral dysplasias and carcinomas should be reassessed.

PMID- 15583544
TI  - HPV DNA in clinically different variants of oral leukoplakia and lichen planus.
AB  - OBJECTIVES: Our objectives were to determine the prevalence of human
      papillomavirus (HPV) infection in oral leukoplakia (OL) and oral lichen planus
      (OLP) in comparison with that in healthy oral mucosa, also conditionally to age,
      gender, smoking, and drinking habits of patients, so as to investigate any
      possible association of HPV infection with a specific clinical variant of OL or
      OLP. STUDY DESIGN: We did research on HPV DNA in 68 cases of OL (homogeneous form
      [H] in 45 cases and nonhomogeneous form [non-H] in 23 cases), and in 71 cases of
      OLP (nonatrophic/erosive form [non-AE] in 27 cases, atrophic/erosive form [AE] in
      44 cases). HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR
      (nPCR: MY09-MY11/GP5-GP6) and the HPV genotype determined by direct DNA
      sequencing. RESULTS: HPV DNA was found in 17.6% of OL, in 19.7% of OLP, and in
      5.6% of controls, with a statistically significant higher risk of HPV infection
      in both lesion groups (for OL: P=.01; Odds Ratio [OR]=3.64; 95% CI: 1.21-10.80;
      for OLP: P=.005; OR=4.17; 95% CI: 1.41-12.18). Demographic variables analysis
      showed that the only significant association was between HPV status and current
      smoking in OL patients (OR'=3.40; 95% CI: 1.0-11.59). HPV DNA was found in 20% of
      H OL and 13% of non-H OL, without any association with the clinical variant
      (P=.73; OR=0.60; 95% CI: 0.14-2.48). HPV DNA was found in 18.5% of non-AE OLP and
      20.4% of AE OLP, without any significant association with the clinical variant
      (P=.84; OR=1.13; 95% CI: 0.335-3.816). HPV-18 was the most frequently detected
      genotype (9/12 and 10/14 of HPV-positive OL and OLP, respectively), followed by
      HPV-16 (2/12 OL and 2/14 OLP), HPV-33 (1/12 OL), HPV-31 (1/14 OLP), and HPV-6
      (1/14 OLP). CONCLUSIONS: An increased risk of HPV infection was found in OL and
      OLP; however, no specific clinical variant of OL or OLP was noted to be
      associated with HPV infection. It is not possible to predict the likelihood of
      HPV infection from the clinical features of OL and OLP.

PMID- 15583545
TI  - Unilateral agenesis of the parotid gland: a case report.
AB  - Agenesis of the parotid gland is an extremely rare condition and may be partial
      or total, unilateral or bilateral, and may occur on its own or associated with
      other developmental abnormalities. We report a case of unilateral agenesis of the
      parotid gland without involvement of other major salivary glands together with a
      compensatory hypertrophy of the contralateral parotid gland.

PMID- 15583546
TI  - Validity of multislice computerized tomography for diagnosis of maxillofacial
      fractures using an independent workstation.
AB  - OBJECTIVE: The purpose of this study was to demonstrate the sensitivity and
      specificity of multislice computerized tomography (CT) for diagnosis of
      maxillofacial fractures following specific protocols using an independent
      workstation. STUDY DESIGN: The study population consisted of 56 patients with
      maxillofacial fractures who were submitted to a multislice CT. The original data
      were transferred to an independent workstation using volumetric imaging software
      to generate axial images and simultaneous multiplanar (MPR) and 3-dimensional (3D
      CT) volume rendering reconstructed images. The images were then processed and
      interpreted by 2 examiners using the following protocols independently of each
      other: axial, MPR/axial, 3D-CT images, and the association of axial/MPR/3D
      images. The clinical/surgical findings were considered the gold standard
      corroborating the diagnosis of the fractures and their anatomic localization. The
      statistical analysis was carried out using validity and chi-squared tests.
      RESULTS: The association of axial/MPR/3D images indicated a higher sensitivity
      (range 95.8%) and specificity (range 99%) than the other methods regarding the
      analysis of all regions. CONCLUSION: CT imaging demonstrated high specificity and
      sensitivity for maxillofacial fractures. The association of axial/MPR/3D-CT
      images added important information in relationship to other CT protocols.

PMID- 15583547
TI  - Interpretation of the origin of a submandibular mass by CT and MRI imaging.
AB  - OBJECTIVE: To clarify the useful findings for determining whether the
      submandibular mass is intraglandular or extraglandular. STUDY DESIGN: Forty-eight
      patients with swelling of the submandibular region were reviewed. The
      relationship between the lesion and the submandibular gland and the displacement
      of the anterior facial vein were analyzed. RESULTS: The accuracy of the
      predictions based on the relationship between the lesion and the submandibular
      gland (SMG) was 87% on contrast-enhanced CT (CECT), 85% on CT sialography (CTS),
      and 91% on MRI. Although the displacement of the facial vein outside the lesion
      suggested an intraglandular lesion, and inside the lesion suggested an
      extraglandular lesion, these were not sufficient to differentiate the lesions in
      7 out of 23 CECT cases and 4 out of 11 MRI cases. CONCLUSION: The finding of a
      relationship between the lesion and the SMG is the most important finding of this
      study.

PMID- 15583548
TI  - Extraoral imaging for proximal caries detection: Bitewings vs scanogram.
AB  - OBJECTIVE: The objective of this study was to compare the diagnostic accuracy of
      3 extraoral imaging modalities with an intraoral bitewing radiograph for proximal
      caries detection. STUDY DESIGN: Three modalities of Cranex TOME scanograms, x-ray
      film and DenOptix photostimulable phosphor plates with and without digital
      enhancement, were compared with Insight intraoral radiographs for proximal caries
      detection. Nine observers evaluated images of the proximal surfaces of 45
      extracted posterior teeth. The presence or absence of caries was scored using a 5
      point confidence scale. The ground truth was determined from histological
      sections. Responses were evaluated by repeated measures analysis of variance
      (ANOVA) for areas under receiver operating characteristic (ROC) curves (A z ).
      RESULTS: Repeated measures ANOVA (at alpha = 0.05) demonstrated significant
      differences among modalities ( P = .041). Paired t tests with Bonferroni
      correction demonstrated that Insight was superior to only unenhanced digital
      scanograms ( P = .003). Mean A z scores (+/-SD) were 0.73 (+/-0.08) for Insight,
      0.65 (+/-0.06) for screen/film scanogram, 0.64 (+/-0.04) for unenhanced digital
      scanogram, and 0.66 (+/-0.07) for enhanced digital scanogram. CONCLUSIONS: The
      performances of film-based and enhanced digital scanograms were not statistically
      different from Insight film for proximal caries detection. Unenhanced digital
      scanograms exhibited a statistically significant lower diagnostic accuracy than
      Insight film.

PMID- 15583549
TI  - Ultrasonographic appearance of lipoma in the oral and maxillofacial region.
AB  - OBJECTIVE: To summarize the clinical situation, ultrasonographic appearance,
      diagnosis, and treatment experience of lipoma in the oral and maxillofacial
      region. STUDY DESIGN: Twenty-two patients with lipoma in the oral and
      maxillofacial region were retrospectively investigated in regards to clinical
      appearance, ultrasonographic appearance, and treatment. RESULTS: Among the 22
      patients, the ratio between males and females was 2.67:1. The age ranged from 21
      to 72 years with a mean age of 47 years. The most common location was the
      submandibular region. Ultrasonographic appearance of lipoma in the oral and
      maxillofacial region was round or elliptical in shape with intact or mostly
      intact capsule. The internal architecture in the majority of patients was
      hypoechoic with echogenic lines or spots. Complete surgical resection was
      performed, and no recurrence occurred during the follow-up period. CONCLUSION:
      Diagnosis of lipoma in the oral and maxillofacial region can be made based on the
      clinical examination and ultrasonography. Complete surgical resection is the
      treatment of choice.

PMID- 15583550
TI  - Denaturing gradient gel electrophoresis analysis of bacterial communities
      associated with failed endodontic treatment.
AB  - OBJECTIVE: A great deal of evidence indicates that persistent infections of the
      root canal of human teeth play an important role in the failure of the root canal
      treatment. The present study was undertaken to apply the PCR-DGGE fingerprinting
      approach to examine the structure of the bacterial population infecting
      previously treated root canals of humans associated with persistent periradicular
      lesions. STUDY DESIGN: Samples were taken from 14 filled root canals, DNA was
      extracted, and part of the 16S rDNA of all bacteria was amplified by PCR and
      separated by DGGE, generating banding patterns representative of the community
      structure. Species-specific PCR for the detection of Enterococcus faecalis was
      also performed. RESULTS: The mean number of bands detected in the 16S rDNA
      community profiles was about 6, ranging from 1 to 26 bands. Each sample showed a
      unique structure of the microbial community. The species-specific PCR assay
      revealed the presence of E. faecalis in 10 of 14 samples, but DGGE analysis
      revealed it was not the dominant species. CONCLUSIONS: Results revealed that the
      intraradicular bacterial community associated with failed endodontic treatment
      significantly varied in composition from teeth to teeth. Persistent
      intraradicular infections were present in all root-filled teeth.

PMID- 15583551
TI  - Use of laser Doppler flowmetry to predict vitality of luxated or avulsed
      permanent teeth.
AB  - OBJECTIVE: Splinting of traumatically displaced or avulsed permanent teeth has
      been described as an effective modality in the treatment of patients with dental
      injuries. The purpose of this study was to investigate whether laser Doppler
      flowmetry (LDF) measurements of pulpal blood flow (PBF) and/or dental injury type
      may predict treatment outcome of splinting of permanent maxillary incisors. STUDY
      DESIGN: The study comprised 64 patients undergoing dental trauma splinting, who
      were characterized by the presence of a single permanent maxillary incisor
      affected by a subluxation, luxation, or avulsion type injury. Perfusion units
      (PU) were taken in 2 sessions, on the day of splint removal (6 weeks after
      trauma; session I) and 12 weeks after splint removal (session II). At each
      session, when an injured permanent maxillary central incisor was recorded, the
      respective contralateral homologous tooth was used as a control. An adverse
      outcome occurring 36 weeks after splint removal was defined as the presence of
      "periapical radiolucency and/or grey discoloration." A multiple logistic
      regression analysis was used to compute the odds ratio for session-related PBF
      characteristics and dental injury type for adverse outcome (n=22) versus
      nonadverse outcome (n=42). RESULTS: There was a significant increase in PBF
      values from session I to session II (P=.047) for teeth without an adverse
      outcome, whereas teeth affected by an adverse outcome showed a significant
      decrease in PBF values (P=.001). PBF measurements did not change over time for
      the control group of contralateral incisors (P=.185). For the outcome criterion
      of "presence of periapical radiolucency and/or grey discoloration," there was a
      significant association between the treatment outcome groups and the variables of
      dental injury type (P=.049), session-related PBF difference (P=.000), and session
      II-related PBF level (P=.000). Significant increase in risk of an adverse outcome
      occurred with a session-related PBF difference (PBF(Session I) - PBF(Session II))
      of >/=0 PU (8.6 odds ratio) (P=.014), and a session II-related PBF level of
      </=2.8 PU (20.2 odds ratio) (P=.030). CONCLUSION: The data suggest the LDF test
      to be a valuable diagnostic adjunct for luxated teeth showing signs of adverse
      outcomes. Predictive modeling may provide clinicians with the opportunity to
      identify "at-risk" teeth early and initiate specific treatments.

PMID- 15583552
TI  - Cytotoxicity evaluation of gutta-percha solvents: Chloroform and GP-Solvent
      (limonene).
AB  - OBJECTIVE: The purpose of this study was to compare the cytotoxicity of 2 gutta
      percha solvents, chloroform and GP-Solvent, on cell line L929. STUDY DESIGN: 2
      gutta-percha solvents were diluted into the concentrations of 1:100, 1:400, and
      1:800. The experiment was done in a 96-well tissue-culture plate. Cell viability
      of L929 was determined after each gutta-percha solvent was left in contact with
      MTT solution for 3 hours. RESULTS: Both solvents proved toxic at the same levels
      of concentrations of 1:100 and 1:400 (P>.05). At the dilution of 1:800 the GP
      Solvent seems to be more toxic than the chloroform (P < .05). CONCLUSIONS: Within
      the limitation of this experiment, GP-Solvent was not less cytotoxic than
      chloroform to the target cells. Because in clinical procedures we use a higher
      concentration of solvent to dissolve gutta-percha for retreatment than that used
      in this study, the overflowing of liquefied gutta-percha, or solvent out of
      apical foramen, should be a cause for concern.

PMID- 15583553
TI  - Russell bodies in dental pulp of permanent human teeth.
AB  - OBJECTIVES: We sought to characterize the prevalence of Russell bodies in
      specimens clinically diagnosed as pulpitis. STUDY DESIGN: Forty-five teeth with
      symptomatic irreversible pulpitis were extracted, fixed, and demineralized. Five
      nonsymptomatic human teeth extracted for orthodontic purposes were used as
      controls. All teeth were then processed for light microscopy, for which they were
      stained variously, or for transmission electron microscopy (TEM). RESULTS: There
      was no evidence of Russell bodies in the pulp of 5 nonsymptomatic human teeth.
      Russell bodies, however, were detected in 31/45 (69%) of pulpitis specimens
      examined by light microscopy. The basic stains safranin and fucsin gave better
      visualisation of them than other staining procedures. All pulpitis specimens were
      histologically characterized as having the features of chronic inflammation. Of 5
      specimens of pulpitis teeth evaluated by TEM, all exhibited Russell bodies. There
      was no morphological distinction among the Russell bodies when view either by
      light or electron microscopy. These structures appeared either within rough
      endoplasmic reticulum (RER) or they were found in extracellular stroma,
      suggesting their association with the lysis of cells. CONCLUSIONS: Russell bodies
      are prevalent in pulpitis samples with histological features of chronic
      inflammation, but are not found in all such samples. Russell bodies may not have
      been frequently detected in the past due to the types of stains employed in
      histolopathological study of pulps. The mechanistic basis of the association of
      Russell bodies with the symptoms of irreversible pulpitis is not clear.

PMID- 15583554
TI  - Evaluation of the factors necessary to develop stability in mandibular dentures.
      1966.

PMID- 15583555
TI  - Restoration of anterior teeth with indirect composite partial coverage crowns: a
      clinical report.
AB  - When an esthetic restoration with minimal tooth reduction is desired, for example
      in patients with uncomplicated tooth fractures, composite partial coverage crowns
      may be a therapeutic option. The indirect composite restoration allows
      restoration of the original tooth anatomy, function, and esthetics to be
      reproduced while preserving tooth structure. The use of composite partial
      coverage crowns to restore fractured anterior teeth is described.

PMID- 15583556
TI  - Evaluation of load transfer characteristics of five different implants in compact
      bone at different load levels by finite elements analysis.
AB  - STATEMENT OF PROBLEM: The external contour of an implant and the magnitude of
      occlusal loading can have significant effects on the load transfer
      characteristics and may result in different bone failure rates for different
      implant systems. PURPOSE: The goal of this study was to investigate the effects
      of external geometry and occlusal load magnitude on bone failure modes for 5
      commercially available dental implant systems. MATERIAL AND METHODS: Five
      different implant systems; Ankylos, Astra, Bicon, ITI, and Nobel Biocare,
      comparable in size, but different in thread profile and crest module shapes, were
      compared using the finite element method. Type II bone quality was approximated
      and complete osseous integration was assumed. Occlusal loads of varying
      magnitudes (0 to 2000 N) were applied on the abutments supporting single tooth
      restorations at 11.3 degrees from the vertical axis with a 1-mm offset. Total
      overloaded bone area, where tensile and compressive normal stresses fell outside
      of the recommended limits of 100 and 170 MPa, respectively, was investigated for
      different load levels. RESULTS: For moderate levels of occlusal loads up to 300
      N, the compact bone was not overloaded by any of the implant systems. At the
      extreme end of the occlusal load range (1000 N or more) the overloading
      characteristics of implants may be dependent on geometric shape. CONCLUSION: In
      general, overloading occurs near the superior region of compact bone, in
      compression, and it is primarily caused by the normal and lateral components of
      the occlusal load. At the region of intersection of compact and trabecular bone,
      overloading occurs in tension due to the vertical component of the occlusal load.
      For excessive forces greater than 1000 N, the overloaded areas of the bone varied
      considerably among 5 different implants systems evaluated.

PMID- 15583557
TI  - The shortened dental arch: a review of the literature.
AB  - The functional demands of patients are highly variable and individual, requiring
      dental treatment to be tailored to the individual's needs and adaptive
      capability. The World Health Organization indicates that a functional, esthetic,
      natural dentition has at least 20 teeth, while the literature indicates that
      dental arches comprising the anterior and premolar regions meet the requirements
      of a functional dentition. The English-language peer-reviewed literature
      pertaining to the short dental arch (SDA) was identified through the Medline
      search engine covering the period between 1966 and the present and critically
      reviewed. This treatment option for the partially dentate patient may provide
      oral functionality, improved oral hygiene, comfort, and, possibly, reduced costs.

PMID- 15583558
TI  - An evaluation of the curve of Spee in the maxilla and mandible of human permanent
      healthy dentitions.
AB  - STATEMENT OF PROBLEM: The characteristics of the curve of Spee in the mandibular
      arch have been extensively investigated. However, few studies have examined the
      characteristics of the curve of Spee in the maxillary arch. PURPOSE: The purpose
      of this study was to examine the differences in the curve of Spee between the
      maxillary and mandibular arches. The effects of gender on the curve of Spee were
      also investigated. Material and methods Fifty Japanese adults (25 men and 25
      women) with permanent healthy dentitions participated. Standardized digital
      pictures of the right side of maxillary and mandibular dental casts were made
      with a digital camera. The cusp tips of the molars, premolars, and canines of the
      maxilla and mandible were identified. The radius and the depth of the curve of
      Spee were measured on the dental casts by means of computer software
      (Occlcircle). The Mann-Whitney test and the Wilcoxon signed rank test were used
      to test the statistical significance (alpha=.05). RESULTS: The curve of Spee
      showed a mean radius of approximately 106.4 mm in the maxillary arch and 83.4 mm
      in the mandibular arch. Radii of the curves of Spee in the maxillary arch were
      significantly larger than those in the mandibular arch (P <.0001) and had a depth
      of approximately 1.6 mm in the maxillary arch and 1.9 mm in the mandibular arch.
      The depth of the curve of Spee in the mandibular arch was significantly deeper
      than that in the maxillary arch (P =.0326). CONCLUSIONS: The curve of Spee was
      not influenced by the gender of the subjects investigated. The shape of the curve
      of Spee in the maxillary arch was significantly flatter than that in the
      mandibular arch.

PMID- 15583559
TI  - Lactic acid root canal irrigation for dowel and core treatment: a pilot study.
AB  - STATEMENT OF PROBLEM: Various solutions used to irrigate root canals and remove
      the smear layer prior to obturation of a root canal affect surface topography and
      may influence the sealing ability of endodontic therapy, retention of endodontic
      dowels, and restoration survival. PURPOSE: This study microscopically evaluated
      the effects of varying dilutions of lactic acid on the removal of the smear layer
      created by hand instrumentation in the coronal, middle, and apical thirds of root
      canals. Lactic acid solution was compared with other solutions deemed to be
      suitable root canal irrigants. MATERIAL AND METHODS: Thirty-five extracted human
      single-rooted teeth were manually shaped with files (K-flex) using the step-back
      technique. ISO size 50 files were used as master apical files. The teeth were
      equally divided into 7 test groups according to the canal irrigant used. While
      the teeth were cleaned and shaped, the root canals were irrigated with 3 mL of 1
      of the following irrigants between each file size and as a final flush: no
      irrigant (control), 5% hydrogen peroxide, 5% sodium hypochlorite, a combination
      of 5% hydrogen peroxide and 5% sodium hypochlorite, 15%
      ethylenediaminotetraacetic acid (EDTA), 10% lactic acid, or 20% lactic acid.
      Specimens were critical-point dried and freeze-fractured for scanning electron
      microscope analysis at 3 sites (cervical, middle, and apical). RESULTS: Scanning
      electron micrographs showed no differences between the cervical, middle, and
      apical levels of the specimens tested with any of the irrigants used. Also, no
      difference was found within individual groups. The surface of the control
      specimens had a smear layer that contained smear plug material. Hydrogen peroxide
      and sodium hypochlorite used separately and in combination consistently produced
      surfaces with a smear layer. Lactic acid solutions and EDTA, however, removed the
      dentinal smear layer but left remnants of smear plugs in the dentinal tubules.
      CONCLUSIONS: Within the limitations of this study, differences related to the
      type of irrigant used were found in the characteristics of the pulpal dentin
      surface. Although lactic acid effectively cleaned and smoothed the dentin walls
      of root canals of endodontically prepared teeth, further study is needed before
      this procedure can be recommended for routine clinical use.

PMID- 15583560
TI  - Effect of margin location on crown preparation resistance form.
AB  - STATEMENT OF THE PROBLEM: The location of preparation margins may compromise the
      fixed prosthodontic restoration's resistance form. Purpose This study evaluated
      changes of opposite wall margin position on rotational resistance form compared
      to the equal-height margin configuration. MATERIAL AND METHODS: The trigonometric
      computation of the minimal resistance form preparation taper, alpha1 , was
      determined using a previously described formula. The alpha1-values for different
      tooth sizes with variation of base widths (range 4 to 10 mm) and vertical wall
      heights (range 4 to 9 mm) were calculated. The alpha1-values represent resistance
      form with both opposing wall margins at the same vertical height position. The
      alpha2-values were calculated with additional formulas to address uneven margin
      heights. Calculated alpha2-values of 10 degrees or less were considered
      clinically significant due to the known level of difficulty for the clinician.
      RESULTS: As a general trend, the alpha2-values were reduced compared to the
      alpha1-values with shortening opposing vertical wall heights in all tooth-size
      categories. Clinically significant changes in the resistance form taper were
      shown in all tooth size categories except the smallest 4-mm tooth base size.
      CONCLUSION: Fixed prosthodontic restoration resistance form is negatively
      affected by uneven vertical margin placement. This phenomenon reduces the
      resistance form of the restoration compared to equal-height margin placement.

PMID- 15583561
TI  - Influence of cyclic loading and luting agents on the fracture load of two all
      ceramic crown systems.
AB  - STATEMENT OF PROBLEM: Inherent mechanical properties, fabrication techniques,
      luting agents, and intraoral conditions are primary factors attributing to
      longevity of all-ceramic crowns. Before doing time-consuming and costly clinical
      studies, preclinical in vitro studies should be conducted to evaluate the
      durability of these crowns. Purpose This study investigated the influence of
      different luting agents and cyclic loading under wet conditions on the fracture
      load of CAD-CAM and pressable all-ceramic crowns. MATERIAL AND METHODS: Ninety
      six human premolars were prepared for all-ceramic crowns with the following
      preparation criteria: 6-degree axial taper, 1.5-mm shoulder finish line placed
      0.5 mm occlusal to the CEJ, 2-mm occlusal reduction, and occluso-gingival height
      of 5 mm. Sixteen unprepared premolars served as controls. Forty-eight crowns were
      laboratory fabricated from a lithium disilicate glass-ceramic (IPS-Empress 2),
      while 48 CAD-CAM crowns were directly fabricated using a leucite-reinforced glass
      ceramic (ProCAD) and the Cerec 3 CAD-CAM system. Three luting agents (Panavia F,
      Superbond C&B and ProTec CEM) were used for cementation (n = 16). After 1 week
      storage in water, half of the specimens of each subgroup (n = 8) were cyclically
      loaded and thermal cycled under wet conditions for 600,000 masticatory cycles and
      3500 thermal cycles (58 degrees C/4 degrees C; dwell time 60 seconds) in a
      masticatory simulator. All specimens were loaded in a universal testing machine
      with the compressive load (N) applied along the long axis of the specimen at a
      crosshead speed of 1 mm/min until fracture. Fracture load was recorded for each
      specimen. The Kruskal-Wallis test was used first to detect overall significance,
      followed by Mann-Whitney U tests to identify which pairs of groups had
      significant differences (P =.05). RESULTS: Cyclic loading significantly decreased
      the median fracture load of ProCAD crowns luted using Superbond from 987.2 to
      786.0 N (P =.014) and those luted using ProTec CEM from 914.4 to 630.7 N (P
      =.007). Also, the median fracture load of Empress 2 crowns luted using ProTec CEM
      decreased significantly from 977.3 to 622.9 N (P =.013). However, cyclic loading
      did not decrease the median fracture load of crowns luted using Panavia F,
      Empress 2 (P =.431) and ProCAD (P =.128). With the same loading conditions and
      luting agents, there were no significant differences in the fracture loads of
      ProCAD and Empress 2 crowns (P >.05). CONCLUSIONS: Cyclic loading reduced the
      fracture load of ProCAD crowns luted with Superbond C&B and ProTec CEM and of
      Empress 2 crowns luted with ProTec CEM.

PMID- 15583562
TI  - Contemporary materials and technologies for all-ceramic fixed partial dentures: a
      review of the literature.
AB  - High-strength all-ceramic systems for fixed partial dentures (FPDs) are available
      for replacing a missing tooth. New core/framework materials have been developed
      and have evolved in the last decade. With the advancement of CAD/CAM technology,
      various fabrication techniques have been developed for fabricating improved,
      consistent, and predictable restorations in terms of strength, marginal fit, and
      esthetics and for managing core/framework materials that could not otherwise be
      managed. This article reviews the evolution and development of materials and
      technologies for all-ceramic FPDs through data published between 1966 and 2004 in
      the English language. Peer-reviewed articles were identified through a MEDLINE
      search and a hand search of relevant textbooks and annual publications. The
      available information suggests that clinical data on the success of these
      restorations are limited, and that the results of long-term clinical studies are
      critical to the assessment of these restorations to provide more specific
      guidelines for usage.

PMID- 15583563
TI  - Morphologic comparison of two neutral zone impression techniques: a pilot study.
AB  - STATEMENT OF PROBLEM: Several studies have compared dentures fabricated using
      neutral zone and conventional techniques. However, studies comparing swallowing
      and phonetic techniques for assessing the location and shape of the neutral zone
      could not be identified in the literature. PURPOSE: The purpose of this pilot
      study was to compare the outline form of the phonetic and swallowing neutral zone
      impression techniques for the same subjects. MATERIAL AND METHODS: Nine denture
      wearers with advanced mandibular ridge resorption were included in this study.
      For each subject 2 trays were prepared in autopolymerizing acrylic resin. One
      method used phonetics and tissue conditioner to shape the neutral zone; the
      second method used swallowing and modeling plastic impression compound. The
      resulting neutral zone impressions were leveled to the same occlusal height by
      gently grinding the occlusal surface on sandpaper until it corresponded with
      landmarks (corners of the mouth, two thirds of the height of the retromolar pads,
      bilaterally) noted on the cast. The impression was inverted onto graph paper, and
      the contour was outlined with a lead pencil. One impression was made for each
      subject, for each technique. The buccal contours of both neutral zones coincided
      at the median line. The maximum distance between the zones was measured in a
      buccolingual direction in the anterior, premolar, and molar regions bilaterally.
      When the location of the phonetic neutral zone in relation compared to the
      swallowing neutral zone was buccally oriented, a plus score was given. When the
      phonetic neutral zone was lingually located, a minus score was given. When the 2
      lines coincided, a score of 0 was given. Measurements were made from direct
      readings on the graph paper. Statistical analysis was performed using the Sign
      test (alpha=.05). RESULTS: Significant differences were noted buccally in the
      left molar (P =.031) and right molar (P =.003) regions and also in the left and
      right premolar regions (P =.007), where the swallowing neutral zone was found to
      be located buccal to the phonetic neutral zone. Significant differences were also
      noted lingually, in the right premolar region (P =.015), where the swallowing
      neutral zone was found to be located lingual to the phonetic neutral zone. There
      was no significant difference between the techniques for the anterior region.
      CONCLUSION: Within the limits of this study, the phonetic neutral zone appears to
      be narrower posteriorly compared to the swallowing neutral zone, thus limiting
      premolar and molar positioning.

PMID- 15583564
TI  - Surgical templates for prosthetically guided implant placement.
AB  - The article describes a prosthetically guided method for the fabrication of
      surgical templates for partially edentulous patients. A number of stainless steel
      components are used to capture the optimal prosthetic position for the placement
      of the implant determined from a diagnostic arrangement. A radiopaque stainless
      steel guide sleeve is used to guide the drill in preparation of the osteotomy
      after radiographs are made to verify the position and proposed trajectory of the
      guide sleeve.

PMID- 15583565
TI  - An implant impression technique using a plaster splinting index combined with a
      silicone impression.
AB  - This article describes a technique for making implant impressions designed to
      reduce framework misfit. The 2-stage impression technique combines the use of
      plaster and a silicone impression material. The method can be used for either
      completely or partially edentulous patients.

PMID- 15583566
TI  - Fabrication of a cement- and screw-retained implant prosthesis.
AB  - The advantages of cement-retained implant-supported restorations over screw
      retained implant restorations are well documented. Difficulty with prosthesis
      retrieval and excess cement removal may be experienced with cemented
      restorations. The technique described allows for the fabrication of a retrievable
      cemented prosthesis that is simple, practical, and effective.

PMID- 15583567
TI  - A technique for restoring an overflared root canal in an anterior tooth.
AB  - This article describes a technique for fabricating a dowel and core for a tooth
      with an overflared root canal. The technique involves supporting a glass fiber
      reinforced prefabricated dowel with chopped silanated glass fibers.

PMID- 15583568
TI  - A technique for fabrication of a provisional fixed partial denture for
      nonparallel abutments.
AB  - A satisfactory provisional fixed partial denture (FPD) should provide positional
      stability, maintain the occlusion, and place an additional load on the abutments
      so that if sensitivity develops, it will subside before the insertion of the
      definitive FPD. This article presents a technique using an indirect-direct
      procedure for the fabrication of a 2-part provisional FPD, utilizing a
      commercially available stainless steel wrought-wire clasp with an occlusal rest,
      which fulfills all the requirements of a provisional FPD.

PMID- 15583569
TI  - Incorporation of microchips to facilitate denture identification by radio
      frequency tagging.
AB  - This article describes a technique for placing a radio-based tagging transponder
      into a complete denture. The data stored in the transponder can be detected with
      a reading device, thus enabling the denture wearer to be identified.

PMID- 15583570
TI  - CAD-CAM generated ear cast by means of a laser scanner and rapid prototyping
      machine.
AB  - Sculpting a wax ear cast for use when making a definitive prosthesis for a
      patient who has had auricle ablative surgery, is challenging. It requires a
      skilled anaplastologist along with complex instrumentation able to perform facial
      laser scans and reproduce anatomic details. The aim of this article is to present
      a technique to create a cast by laser scanning a stone cast of the existing ear.
      A 3D laser scanner develops an integrated 3D digital image of the unaffected ear,
      which is copied and then mirrored. A rapid prototyping machine collects the
      necessary data to manufacture the definitive resin ear. This procedure is time
      and cost effective only if the technology is free of charge.

PMID- 15583571
TI  - Use of vinyl polysiloxane for the fabrication of implant surgical guide.

PMID- 15583572
TI  - Use of a reline jig to fabricate a complete denture implant surgical guide from
      an existing complete denture.

PMID- 15583573
TI  - Adaptation of fiber-reinforced strip using dental floss for the direct splinting
      technique.

PMID- 15583574
TI  - Interocclusal record for fixed implant-supported prosthesis.

PMID- 15583575
TI  - Simple instrument for auscultation of temporomandibular joint sounds.

PMID- 15583576
TI  - Management of autoimmune bullous diseases: pharmacology and therapeutics.
AB  - Bullous diseases are associated with high morbidity and mortality. They result
      from autoimmune response to one or more components of the basement membrane or
      desmosomes. Management consists of treating the immunologic basis of the disease,
      treating the inflammatory process involved in lesion formation, and providing
      supportive care both locally and systemically. Therapeutic agents are chosen
      based on their known pharmacologic properties and evidence of effectiveness
      derived from observations and studies. Learning objectives At the completion of
      this learning activity, participants should be able to understand the
      pharmacology of drugs used in the treatment of bullous diseases, the principles
      of therapy for various such diseases, and a practical approach to the management
      of these diseases.

PMID- 15583577
TI  - Risk factors associated with striae gravidarum.
AB  - BACKGROUND: Striae gravidarum (SG) is a poorly characterized but common
      disfiguring condition of pregnancy. OBJECTIVE: To better characterize the
      epidemiological factors associated with SG. METHODS: An anonymous survey
      administered at Stanford Ambulatory Clinics sampled 161 women who had given
      birth. RESULTS: Forty-eight-point-three percent of women with SG (43/89) versus
      19.4% without SG (14/72) reported mothers with SG (odds ratio = 7.0, 95%
      confidence interval [CI] 2.7, 18.6). Forty-seven percent of women with SG (42/89
      women) versus 18.1% without SG (13/72) reported additional relatives with SG
      (odds ratio = 7.2, 95% CI 2.9, 18.2). Eighty-one percent of women with SG (68/84)
      versus 30.5% without SG (18/59) reported a history of breast or thigh striae
      (odds ratio = 8.6, 95% CI 3.8, 19.9). Forty-seven percent of women with SG versus
      17% without SG were non-white (odds ratio = 4.2, 95% CI 1.9, 9.6). CONCLUSION:
      This study suggests that a history of breast or thigh striae, family history, and
      race is significantly predictive of SG development.

PMID- 15583578
TI  - Comparative analysis of methods for detection of anti-laminin 5 autoantibodies in
      patients with anti-epiligrin cicatricial pemphigoid.
AB  - BACKGROUND: Anti-epiligrin cicatricial pemphigoid (AECP) is a subepidermal
      blistering disease characterized by circulating anti-basement membrane
      autoantibodies to laminin 5. OBJECTIVE: To evaluate the relative sensitivity of
      immunoblotting and immunoprecipitation techniques for the detection of anti
      laminin 5 antibodies, comparative studies using reference laminin 5 antiserum as
      well as sera from patients with AECP, other immunobullous diseases, and normal
      volunteers were performed. METHODS: Equivalent amounts of protein from five
      different substrates were studied by immunoblotting; immunoprecipitation
      experiments examined biosynthetically radiolabeled human keratinocyte (HK)
      extracts. Results HK extracellular matrix (ECM) was the most sensitive substrate
      for detection of antibodies to laminin 5; extracts of HKs, A-431 cells and HaCat
      cells represented alternative test substrates (though the later required higher
      amounts of protein input). Sera from patients with AECP immunoblotted laminin 5
      in HK ECM at end titers exceeding those identified in indirect immunofluorescence
      microscopy studies of 1 M NaCl split skin. Immunoprecipitation studies found that
      a 10,000-fold dilution of reference laminin 5 antiserum retained the ability to
      identify laminin 5. Maximal dilutions of sera from AECP patients retaining the
      ability to immunoprecipitate laminin 5 ranged from 500 to 5,000. CONCLUSION:
      Immunoprecipitation was the most sensitive technique for detection of anti
      laminin 5 antibodies, while immunoblotting of HK ECM or HK extracts represented
      practical alternatives.

PMID- 15583579
TI  - Measurement of itch using actigraphy in pediatric and adult populations.
AB  - We have studied nocturnal movements using wrist-worn accelerometers in 33 adults
      with a range of pruritic dermatoses, 30 adult control subjects, 25 children with
      atopic dermatitis, and 17 pediatric control subjects. In all, 26 adults and 20
      children were studied on more than one occasion, up to a maximum of 6 occasions.
      Participants were examined and a range of subjective measures about the extent of
      skin disease, itch, and quality of sleep were recorded. We show clear differences
      between patients and control subjects for both age groups studied, with activity
      medians approximately twice as high in the patients as in the control subjects (
      P < .001). Studies on the same person show a considerable night-to-night
      variation that is unlikely to relate to measurement error, but instead, we
      believe, reflect genuine differences in nocturnal activity (and perhaps disease
      severity). Movement through the night did not seem to follow any obvious pattern.
      The relation between subjective measures, Severity sCORing of Atopic Dermatitis
      (SCORAD) index scores, and objective recorded activity was imperfect, with much
      unaccounted for variation. In particular, in adults, but not in children, we
      found a negative correlation (-0.44, P < .02) between objective movement activity
      and self-reported quality of sleep. Our results support the use of objective
      measures of scratch in the assessment of disease activity, and suggest that the
      relation between subjective and objective measures of disease severity may not be
      straightforward.

PMID- 15583580
TI  - Atopic dermatitis, stinging, and effects of chronic stress: a pathocausal study.
AB  - BACKGROUND: Patients with atopic dermatitis (AD) often have increased skin
      sensitivity and this symptom often worsens during stress. OBJECTIVE: We sought to
      find out whether patients with AD had stinging, and to identify the pathocausal
      neuroimmune mechanisms, including the role of stress. METHODS: In all, 25
      patients with AD with histories of stress worsening were tested using a stinger
      test. Skin biopsy specimens were processed for immunohistochemistry. Stress
      inquiries and salivary cortisol tests were performed. RESULTS: In all, 16
      patients were stinger-positive and 9 were negative. The stinger-positive
      papillary dermis had an increased number of mast cells, vasoactive intestinal
      polypeptide-positive fibers, and a tendency to a higher number of substance P
      positive nerve fibers, but a decrease of calcitonin gene-related peptide fibers.
      Patients who were stinger-positive had a tendency to lower salivary cortisol.
      CONCLUSIONS: The majority of patients with AD experience stinging. Substance P,
      calcitonin gene-related peptide, vasoactive intestinal polypeptide, and mast
      cells may have a pathocausal role, as might chronic stress.

PMID- 15583581
TI  - Tattoo removal among Ethiopian Jews in Israel: tradition faces technology.
AB  - BACKGROUND: Many Jews in Ethiopia adopted the Christian custom of tattooing
      various parts of the body, either after conversion or to hide their Jewish
      origin. After emigrating to Israel, they sought to remove these foreign symbols
      to better blend with society. The aim of this study was to describe the use of
      laser technology for tattoo removal in a high-risk dark-skinned population and to
      highlight one way in which the interaction of modern medical communities with
      people from developing countries can open new avenues of research. PATIENTS AND
      METHODS: The study sample consisted of 401 women and 3 men of Ethiopian origin
      with Fitzpatrick skin type V or VI. Ages ranged from 15 to 53 years. All tattoos
      were blue/black and had been made by injecting charcoal into the skin. Most (n =
      392, 97%) were located on the forehead or the forehead and temples (n = 312); 69%
      were cross-shaped. Patients underwent 3 to 6 laser treatments (average 3.6) with
      the Q-switched Nd:YAG (n = 380, 94%) or ruby (n = 24) laser at intervals of at
      least 8 weeks. The percent of clearing was scored by two independent
      investigators as follows: 1 = 0%-25%; 2 = 26%-50%; 3 = 51%-75%; 4 = 75%-100%.
      Pigmentary and textural changes were classified as none, mild, moderate, or
      severe. The duration of follow-up after the last treatment was 6-8 months.
      RESULTS: At the last follow-up, the clearance score was 4 in 92% of the patients
      and 3 in the remainder. Transient (2-4 months) mild hyperpigmentation was noted
      in 177 (44%) patients, and mild textural changes in two, both treated with the Q
      switched laser. There were no cases of scarring or permanent pigmentary changes.
      CONCLUSION: Laser removal of carbon-based tattoos in an Ethiopian population
      yielded an excellent to good aesthetic outcome with no complications, similar to
      results in light-skinned patients. These findings have important implications for
      improving the quality of life of Ethiopian immigrants in Israel.

PMID- 15583582
TI  - Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human
      skin.
AB  - BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an
      oral photoprotective agent would have substantial benefits. Objective We
      investigated the photoprotective effect of oral administration of an extract of
      the natural antioxidant Polypodium leucotomos (PL). METHODS: A total of 9 healthy
      participants of skin types II to III were exposed to varying doses of artificial
      UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours
      after exposure the erythema reaction was assessed and paired biopsy specimens
      were obtained from PL-treated and untreated skin. RESULTS: A significant decrease
      in erythema was found in PL-treated skin (P < .01). Histologically, PL-treated
      biopsy specimens showed less sunburn cells (P < .05), cyclobutane pyrimidine
      dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast cell
      infiltration (P < .05). A trend toward Langerhans cell preservation was seen.
      CONCLUSION: Oral administration of PL is an effective systemic
      chemophotoprotective agent leading to significant protection of skin against UV
      radiation.

PMID- 15583583
TI  - Chronic stress accelerates ultraviolet-induced cutaneous carcinogenesis.
AB  - BACKGROUND: Physical and emotional stressors have been found to mediate a wide
      variety of biological changes including the facilitation of tumor progression;
      however most of these paradigms utilized artificial sources of neoplasms and
      stress. METHODS: Skh mice were exposed to carcinogenic doses of ultraviolet light
      (UV). The stressed group was subjected to the close proximity of fox urine as a
      source of stress from the presence of the odor of their natural predator, while
      the control group remained stress free. RESULTS: A significant acceleration in
      the development of cutaneous neoplasms was observed in mice that had been exposed
      to the stressor. The first tumor appeared in the group after 8 weeks, whereas
      nonstressed mice began to develop these by week 21. CONCLUSION: These results
      suggest that stress plays a role in potentiating cutaneous carcinogenesis.

PMID- 15583584
TI  - Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo
      diagnosis of basal cell carcinoma: a multicenter study.
AB  - BACKGROUND: The current standard diagnostic procedure for basal cell carcinoma
      (BCC) is histologic examination after invasive biopsy. Reflectance-mode confocal
      microscopy (RCM) offers noninvasive high-resolution imaging of human skin in
      vivo. OBJECTIVE: The objective of this study was to explore the sensitivity and
      specificity of RCM for diagnosis of BCC. METHODS: This was a retrospective study
      of RCM images from 4 institutions of 152 skin lesions representing a variety of
      benign and malignant diagnoses. These 152 lesions were examined clinically, with
      biopsies recorded for all the 83 BCCs detected. Based on a previous study, a set
      of 5 histologically correlated confocal imaging criteria for diagnosing BCC was
      established, eg, the presence of elongated monomorphic nuclei. Blinded
      retrospective analysis of the images from the 152 lesions was carried out by a
      single novice reviewer to determine the sensitivity and specificity of these 5
      RCM criteria for diagnosing BCC. The accuracy of combining the probability of BCC
      based on examination of clinical photographs with the predicted probability of
      BCC based on confocal criteria was also evaluated. RESULTS: The presence of two
      or more criteria is 100% sensitive for the diagnosis of BCC, and with 4 or more
      RCM criteria present the specificity was 95.7% and sensitivity was 82.9%. These
      results were found to have little variability across study sites and across BCC
      subtypes. The combination of RCM with photography-based predictions of clinical
      probability of BCC significantly improved the accuracy for noninvasive diagnosis
      of BCC. CONCLUSION: RCM offers a sensitive and specific tool for the noninvasive
      diagnosis of BCC in vivo.

PMID- 15583585
TI  - Clinical and histopathologic spectrum of cutaneous Rosai-Dorfman disease in
      Taiwan.
AB  - BACKGROUND: Cutaneous Rosai-Dorfman disease (RDD) is a rare entity of unknown
      origin and is not well documented, especially in Asian populations. OBJECTIVE:
      The purpose of this study was to evaluate the clinical manifestation, diagnostic
      histopathology, clinical course, and response to treatment of cutaneous RDD in
      Taiwan. MATERIALS AND METHODS: This study included 21 patients with cutaneous RDD
      who presented at our institution from 1995 to 2003. Pathologic examinations with
      both hematoxylin-eosin and immunohistochemical stains were reviewed, as were
      associated clinical features and therapeutic methods. RESULTS: None of the 21
      patients with cutaneous RDD had nodal lesions. The clinical manifestation was
      variable, but most commonly involved a central noduloplaque with satellite
      papules. One patient manifested as an ulcerated nodule, something not reported
      previously. Multifocal involvement only occurred in 4 patients. Concurrent
      involvement of uvea or vocal cord occurred in two patients. The most prominent
      histologic feature was a florid and mixed inflammatory infiltration. The
      phagocytosis of inflammatory cells into the cytoplasm of histiocytes, a process
      called "emperipolesis," is a characteristic finding of nodular RDD but usually
      only focally presented in cutaneous ones. Positivity for S-100 protein helped to
      confirm the diagnosis. The most effective treatment was surgical excision of
      solitary lesions. High-dose thalidomide (300 mg/d), but not low-dose, was
      effective to control the extensive cutaneous diseases in two patients. A total of
      3 patients experienced spontaneous remission 1 to 2 years after diagnosis.
      CONCLUSIONS: Cutaneous RDD appeared more frequently in Asian populations than in
      reports from Western countries. The incidence of multifocal involvement in this
      series is much lower than in other literature. Although treatment of disseminated
      cutaneous RDD is difficult, high-dose thalidomide (300 mg/d), which was effective
      in two patients in this series, may be helpful.

PMID- 15583586
TI  - Tretinoin treatment before carbon-dioxide laser resurfacing: a clinical and
      biochemical analysis.
AB  - BACKGROUND: Tretinoin is often prescribed before laser resurfacing in an attempt
      to enhance results. OBJECTIVE: We sought to assess the clinical and biochemical
      effects of preoperative tretinoin use before laser resurfacing. METHODS: Patients
      were randomized to apply tretinoin to one forearm and placebo to the other for 3
      weeks. Patients' photodamaged forearms were focally treated by carbon-dioxide
      laser resurfacing. Biopsy specimens were obtained at baseline and various times
      posttreatment. Real-time polymerase chain reaction technology was used to
      quantify messenger RNA levels of types I and III procollagen and matrix
      metalloproteinases-1, 3, and 9. Wounds were assessed for degree of re
      epithelialization using a computer graphics-generated template. A colorimeter was
      used to quantify postoperative erythema. RESULTS: No substantial differences in
      either biochemical markers or clinical end points were identified between
      tretinoin and placebo pretreated forearms. CONCLUSIONS: We found no evidence of
      enhanced collagen formation, accelerated re-epithelialization, or quicker
      resolution of postoperative erythema with tretinoin pretreatment before laser
      resurfacing.

PMID- 15583587
TI  - Prevention of arthropod-related disease.
AB  - Arthropods of medical importance include vespids, ticks, mosquitoes, mites,
      flies, and fleas. They spread illness as disease vectors, are associated with
      lethal allergic reactions, and produce potentially deadly toxins. Strategies for
      prevention of illness include avoidance, vector reduction programs,
      chemoprophylaxis, and repellents. Strategies must be tailored to regional risks.

PMID- 15583588
TI  - A prospective assessment of bleeding and international normalized ratio in
      warfarin-anticoagulated patients having cutaneous surgery.

PMID- 15583589
TI  - Fibroelastolytic papulosis.

PMID- 15583590
TI  - Becker's nevus syndrome revisited.

PMID- 15583591
TI  - Mucocutaneous pain syndromes.

PMID- 15583592
TI  - An American dermatologist goes to Canada: lessons from a single-payer healthcare
      system.

PMID- 15583593
TI  - Surgical pearl: gauzabrasion--abrading superficial slough with rough dressing
      gauze.

PMID- 15583594
TI  - Surgical pearl: a novel method for dressing changes in interpolation flaps.

PMID- 15583595
TI  - Surgical pearl: the use of a teaspoon during dermal filler injection.

PMID- 15583596
TI  - Surgical pearl: a novel adaptor for cryotherapy.

PMID- 15583597
TI  - Acral persistent papular mucinosis.
AB  - Acral persistent papular mucinosis is a rare subtype of localized lichen
      myxedematosus. For half a century, this disease has endured a controversial and
      constantly evolving classification. We describe a patient who presented with
      discrete, flesh-colored papules on the hands, wrists, and forearms in a
      distribution consistent with acral persistent papular mucinosis. Histology was
      also constant with this disease, showing a well-circumscribed deposition of mucin
      in the upper and mid dermis that spared a small grenz zone. The changing
      nomenclature and diagnostic requirements of acral persistent papular mucinosis
      that have allowed it to remain a topic of debate are examined through a
      comprehensive review of the literature. All reported cases are reviewed.

PMID- 15583598
TI  - Nevoid basal cell carcinoma syndrome or multiple hereditary infundibulocystic
      basal cell carcinoma syndrome?
AB  - We present a case of nevoid basal cell carcinoma syndrome, also known as Gorlin
      syndrome, or basal cell nevus syndrome, which clinically follows a course more
      consistent with multiple hereditary infundibulocystic basal cell carcinomas or
      multiple hereditary trichoepitheliomas. The following article describes the case
      in detail and gives an overview of other genodermatosis, which were initially
      considered in the differential and which may be linked pathogenetically.

PMID- 15583599
TI  - Bull's-eye cutaneous infarct of zygomycosis: a bedside diagnosis confirmed by
      touch preparation.
AB  - We report an immunocompromised woman with chronic lymphocytic leukemia who
      developed cutaneous zygomycosis at the site of an arterial line. The initial
      lesion resembled a bulls-eye. Bull's-eye lesions of zygomycosis have been
      reported twice before. Recognition of this sign may allow the dermatologist to
      make a rapid presumptive diagnosis and initiate treatment for this life
      threatening infection.

PMID- 15583600
TI  - Pruritus, pain, and small nerve fiber function in keloids: a controlled study.
AB  - BACKGROUND: Keloid scars can itch and hurt, but little is known about the
      characteristics of these symptoms in keloids. Because itch and pain are carried
      by small nerve fibers, abnormal function of these fibers could be an explanation
      for such phenomena. OBJECTIVE: We sought to assess the characteristics of itch
      and pain in keloid scars, and to assess the function of small nerve fibers in
      keloids. METHODS: We studied the location and intensity of itch and pain in
      keloids that had been present for at least 1 year. We further studied the
      function of small nerve fibers by assessing allodynia and alloknesis (which are
      pain and itch, respectively) from innocuous stimuli that do not normally provoke
      pain and itch, and we used quantitative thermosensory testing (in keloid lesions,
      perikeloidal skin, and contralateral normal skin as a control). Results In all,
      28 patients (13 men and 15 women) with a mean age of 34 years were enrolled and
      completed the study. Of the patients, 86% experienced itch and 46% experienced
      keloid-related pain. Of those who experienced itch, 92% felt the itch at the edge
      of their keloids. Of the patients with pain, 77% felt pain at the center of the
      keloid. Mechanical allodynia was noted in 43% of the patients, and only 14%
      experienced alloknesis. Abnormal thermosensory thresholds to warmth, cold, and
      heat pain were noted in the keloids. Visual analogue scale of itch correlated
      significantly to warmth ( r = 0.65), heat pain ( r = 0.4), and cold pain ( r = 
      0.41). CONCLUSION: Itch and pain are common presentations in keloids and are
      associated with abnormalities in small nerve fiber function, suggesting a small
      nerve fiber neuropathy.

PMID- 15583601
TI  - Lesional T cells and dermal dendrocytes in psoriasis plaque express increased
      levels of granulysin.
AB  - Granulysin is a broad-spectrum potent antimicrobial peptide produced by the
      immunocytes. We determined granulysin levels in certain cutaneous inflammatory
      diseases and correlated expression of granulysin with the relative risks of
      secondary infections in these conditions. In immunohistochemistry stains a
      monoclonal antigranulysin antibody was used at 1:150 dilutions. Compared with
      atopic dermatitis and nummular eczema lesions where secondary infection with
      Staphylococcus aureus is very common, we found that a significantly increased
      number of granulysin-positive T cells (P < .01) were present in psoriatic
      plaques. Psoriasis plaques are heavily colonized with S aureus . It is a well
      known observation that despite open cracks and fissures these plaques do not get
      infected. Increased levels of granulysin provide an explanation for relative
      immunity of psoriatic plaques against both gram-positive and gram-negative
      bacterial infections.

PMID- 15583602
TI  - DNA-based prenatal exclusion of bullous congenital ichthyosiform erythroderma at
      the early stage, 10 to 11 weeks' of pregnancy, in two consequent siblings.
AB  - The proband was a Japanese woman with bullous congenital ichthyosiform
      erythroderma harboring a keratin 10 gene mutation M150T. DNA-based prenatal
      exclusion of bullous congenital ichthyosiform erythroderma was successfully
      performed in her two consequent pregnancies using chorionic villus samples at 10
      to 11 weeks' gestation, several weeks earlier than the previously reported cases.

PMID- 15583603
TI  - Pemphigus foliaceus with neutrophilic spongiosis evolving to an atypical
      pemphigus phenotype.
AB  - A 46-year-old Brazilian man, with initial pustular lesions, neutrophilic
      spongiosis and subcorneal cleavage evolved to an atypical pemphigus phenotype,
      with suprabasal acantholysis. Interestingly, his autoantibody profile, tested by
      immunofluorescence, immunoblotting, enzyme-linked immunosorbent assay, and
      immunoprecipitation revealed exclusive IgG anti-desmoglein 1 antibodies in all
      phases of the disease.

PMID- 15583604
TI  - Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell
      lymphoma entity?
AB  - Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of
      pityriasis lichenoides et varioliformis acuta (PLEVA). PLEVA patients only very
      rarely have systemic signs; the cutaneous lesions are usually asymptomatic, but
      may be pruritic and may heal with scarring. FUMHD often starts out as classic
      PLEVA, but goes on to develop widespread ulceronecrotic lesions and is associated
      with a high mortality rate. Whether Pityriasis lichenoides chronica (PLC) and
      PLEVA form a spectrum rather than single entities of clonal lymphoproliferative
      diseases has been discussed. Recently, it has been proposed that FUMHD, too, is a
      clonal lymphoproliferative disorder. Here, we report two cases of FUMHD with
      monoclonal T-cell population, as detected by Southern blot analysis. We propose
      that clonal FUMHD represents a cutaneous T-cell lymphoma entity.

PMID- 15583605
TI  - Eruptive disseminated superficial actinic porokeratosis in an immunocompetent
      host: is this associated with herpes simplex virus or bacterial infection?

PMID- 15583606
TI  - Recurrent hemolysis-associated pseudoerysipelas of the lower legs in a patient
      with congenital spherocytosis.
AB  - A 29-year-old patient presented with recurrent erythematous eruptions on both
      lower legs of 15 years' duration. Family history, along with clinical and
      laboratory examinations, revealed congenital hereditary spherocytosis and
      excluded other reasons for the erythematous eruptions of the lower legs. During
      two subsequent episodes, we detected increased hemolysis that disappeared
      concomittantly on spontanous resolution of the lesions. To our knowledge, this
      case is the first report showing a recurrent erythematous eruption on the lower
      legs in a patient with congenital hereditary spherocytosis. These eruptions might
      be caused by intermittent hemolysis-induced inflammation as a result of the
      increased osmotic fragility of the erythrocytes and may evolve to chronic leg
      ulcers later in life.

PMID- 15583607
TI  - Relapsing polychondritis in HIV-infected patients: a report of two cases.
AB  - Relapsing polychondritis is a rare autoimmune disease characterized by
      inflammation and degeneration of cartilaginous tissue. We describe the first
      reported cases of relapsing polychondritis in patients with human
      immunodeficiency virus (HIV) and no associated connective tissue diseases. The
      relationship between autoimmune and HIV diseases is complex and unclear.
      Treatment of HIV disease with antiretroviral therapy and subsequent immune
      restoration may lead to the development of autoimmune diseases in genetically
      susceptible individuals.

PMID- 15583608
TI  - Rapid onset of cutaneous squamous cell carcinoma of the penis in a patient with
      psoriasis on etanercept therapy.

PMID- 15583609
TI  - Intravenous immune globulin in the treatment of persistent pemphigoid
      gestationis.

PMID- 15583610
TI  - Serious dermatologic reaction associated with valdecoxib: report of two cases.

PMID- 15583611
TI  - Cutaneous vasculitis induced by cyclo-oxygenase-2 selective inhibitors.

PMID- 15583612
TI  - A subcutaneous tumor on the forehead of a 12-year-old child: a rare clinical
      presentation of a frontal mucocele.

PMID- 15583613
TI  - Advanced presentation of melanoma in African Americans: the Miami-Dade County
      experience.

PMID- 15583614
TI  - Expression of cysteinyl leukotriene receptor-1 in skin.

PMID- 15583615
TI  - Keratosis lichenoides chronica: mimics, history, nomenclature.

PMID- 15583616
TI  - Unilateral facial angiofibromas and tuberous sclerosis.

PMID- 15583617
TI  - Bacitracin after clean surgical procedures may be risky.

PMID- 15583618
TI  - Oral ivermectin for Phthirus pubis.

PMID- 15583619
TI  - Comment on viral tropical diseases.

PMID- 15583638
TI  - The perils of subsidiarity.

PMID- 15583639
TI  - California votes for embryonic stem cell research.

PMID- 15583640
TI  - Next generation flu vaccine boosted by Chiron debacle.

PMID- 15583641
TI  - IPOs: the narrow window closes?

PMID- 15583642
TI  - FDA and EMEA pool scientific advice.

PMID- 15583644
TI  - Profile: Daniel Callahan.

PMID- 15583645
TI  - The biotech drug market.

PMID- 15583646
TI  - Can China bring its own pipeline to the market?

PMID- 15583648
TI  - No Munich on GM crops.

PMID- 15583649
TI  - Leader sequences are not signal peptides.

PMID- 15583650
TI  - US food safety under siege?

PMID- 15583651
TI  - Nuclear transfer cloning and the United Nations.

PMID- 15583652
TI  - Biotechs for pennies?

PMID- 15583654
TI  - Recombinant protein therapeutics--success rates, market trends and values to
      2010.

PMID- 15583655
TI  - Knocking the SOCS1 off dendritic cells.

PMID- 15583656
TI  - Streptococcal genomes provide food for thought.

PMID- 15583657
TI  - A new harvest of fluorescent proteins.

PMID- 15583658
TI  - Putting the opium in poppy to sleep.

PMID- 15583659
TI  - Baculovirus solves a complex problem.

PMID- 15583660
TI  - Uninhibited antibiotic target discovery via chemical genetics.

PMID- 15583662
TI  - Role of Toll-like receptors in antisense and siRNA [corrected].
AB  - About 25 years ago, researchers first demonstrated that a short synthetic
      oligodeoxynucleotide, referred to as antisense, can inhibit replication of Rous
      sarcoma virus through hybridization to viral RNA. Since then, several
      hybridization-based oligonucleotide approaches have been developed to elucidate
      the functions of genes and their potential as therapeutic agents. Short
      interfering (si) RNA is the most recent example. To effectively inhibit gene
      expression, an antisense or siRNA must be resistant to nucleases, be taken up
      efficiently by cells, hybridize efficiently with the target mRNA and activate
      selective degradation of the target mRNA or block its translation without causing
      undesirable side effects. However, both antisense and siRNA agents have been
      shown to exert non-target-related biological effects including immune
      stimulation. Do antisense and siRNA agents work as ligands for Toll-like
      receptors (TLRs), a family of pathogen-associated, molecular pattern recognition
      receptors?

PMID- 15583670
TI  - Intellectual property law in Israel, and US and European objections: Market
      exclusivity vs. data exclusivity.

PMID- 15583675
TI  - A proposed framework for the description of plant metabolomics experiments and
      their results.
AB  - The study of the metabolite complement of biological samples, known as
      metabolomics, is creating large amounts of data, and support for handling these
      data sets is required to facilitate meaningful analyses that will answer
      biological questions. We present a data model for plant metabolomics known as
      ArMet (architecture for metabolomics). It encompasses the entire experimental
      time line from experiment definition and description of biological source
      material, through sample growth and preparation to the results of chemical
      analysis. Such formal data descriptions, which specify the full experimental
      context, enable principled comparison of data sets, allow proper interpretation
      of experimental results, permit the repetition of experiments and provide a basis
      for the design of systems for data storage and transmission. The current design
      and example implementations are freely available (http://www.armet.org/). We seek
      to advance discussion and community adoption of a standard for metabolomics,
      which would promote principled collection, storage and transmission of experiment
      data.

PMID- 15583676
TI  - What to expect at your biotech job interview.

PMID- 15583678
TI  - Health biotechnology in China--reawakening of a giant.

PMID- 15583679
TI  - Cuba--innovation through synergy.

PMID- 15583680
TI  - The emergence of Egyptian biotechnology from generics.

PMID- 15583681
TI  - Introduction: promoting global health through biotechnology.

PMID- 15583682
TI  - Indian biotechnology--rapidly evolving and industry led.

PMID- 15583683
TI  - South Africa--blazing a trail for African biotechnology.

PMID- 15583684
TI  - South Korean biotechnology--a rising industrial and scientific powerhouse.

PMID- 15583685
TI  - Conclusions: promoting biotechnology innovation in developing countries.

PMID- 15583686
TI  - The scientific muscle of Brazil's health biotechnology.

PMID- 15583687
TI  - Oestrogen-selective modulation of FSH and LH secretion by pituitary gland.

PMID- 15583688
TI  - Atypical cancer pattern in patients with Parkinson's disease.
AB  - Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the
      period 1977-98 identified from the National Register of Patients, 1282 cancers
      were subsequently recorded in the Danish Cancer Registry, compared with 1464
      expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence
      interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking
      related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and
      urinary bladder (0.52), although moderate reductions in risk were also seen for
      several nonsmoking-related cancers. In contrast, increased risks were seen for
      malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer
      (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern
      supports the hypothesis that constituents of tobacco smoke inhibit or delay the
      development of Parkinson's disease, but a low smoking prevalence appears to be
      only part of the explanation for the decreased cancer incidence. The increased
      relative risks of melanoma and nonmelanoma skin cancer are not likely to be
      artefactual, but further investigations of potential mechanisms are warranted.

PMID- 15583689
TI  - The risk of cancer in HIV-infected people in southeast England: a cohort study.
AB  - This study used data from the Communicable Disease Surveillance Centre's national
      HIV database and the Thames Cancer Registry to assess the risk of cancer in HIV
      infected people in southeast England. Among 26 080 HIV-infected men with 158,660
      person-years follow-up, 1851 cancers, and among 7110 HIV-infected women (31 098
      person-years), 171 cancers were identified. The standardised incidence ratio
      (SIR) for all non-AIDS-defining cancers was significantly increased in HIV
      infected men (2.8, 95% confidence interval (CI) 2.6-3.1) but was nonsignificant
      in HIV-infected women (1.1, 95% CI 0.8-1.6). Most of the cancers observed were in
      men (n = 1559) and women (n = 127) with AIDS, and among them, the SIR for all non
      AIDS-defining cancers was significantly increased in men (8.2, 95% CI 7.2-9.2)
      and women (2.8, 95% CI 1.6-4.6). The SIR for all non-AIDS-defining cancers was
      only just significantly increased in men with HIV-infection but not AIDS (1.2,
      95% CI 1.0-1.5) and was nonsignificant in such women (0.8, 95% CI 0.5-1.2).

PMID- 15583690
TI  - p53 polymorphisms associated with mutations in and loss of heterozygosity of the
      p53 gene in male oral squamous cell carcinomas in Taiwan.
AB  - The present study was designed to examine whether different p53 haplotypes of
      exon 4-intron 3-intron 6 affect the frequency of mutations and loss of
      heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas
      (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had
      significantly higher frequency of p53 mutations than those with two Pro-W-G
      alleles (odds ratio (OR) = 1.98; 95% confidence interval (CI), 1.10-3.56). Out of
      the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among
      these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It
      is notable that alcohol drinking increased the frequency of Arg allele loss (OR =
      10.56; 95% CI, 1.23-234.94) in OSCCs from patients who both smoked cigarettes and
      chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53
      mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the
      Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially
      lost in OSCCs associated with cigarette smoking and AQ chewing, while the
      frequency of Arg allele loss is increased with alcohol drinking, and (c)
      haploinsufficiency of p53 is in itself likely to contribute to tumour progression
      in Taiwanese OSCCs.

PMID- 15583691
TI  - A micro costing of NHS cancer genetic services.
AB  - This paper presents the first full micro costing of a commonly used cancer
      genetic counselling and testing protocol used in the UK. Costs were estimated for
      the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a
      questionnaire to all staff, conducting an audit of clinic rooms and equipment and
      obtaining gross unit costs from the finance department. A total of 22 distinct
      event pathways were identified for patients at risk of developing breast,
      ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were
      pound sterling 97- pound sterling 151 for patients at moderate risk, pound
      sterling 975- pound sterling 3072 for patients at high risk of developing
      colorectal cancer and pound sterling 675- pound sterling 2909 for patients at
      high risk of developing breast or ovarian cancer. The most expensive element of
      cancer genetic services was labour. Labour costs were dependent upon the amount
      of labour, staff grade, number of counsellors used and the proportion of staff
      time devoted to indirect patient contact. With the growing demand for cancer
      genetic services and the growing number of national and regional cancer genetic
      centers, there is a need for the different protocols being used to be thoroughly
      evaluated in terms of costs and outcomes.

PMID- 15583692
TI  - Expression analysis onto microarrays of randomly selected cDNA clones highlights
      HOXB13 as a marker of human prostate cancer.
AB  - In a strategy aimed at identifying novel markers of human prostate cancer, we
      performed expression analysis using microarrays of clones randomly selected from
      a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of
      expression profiles in primary human prostate cancer, adjacent normal prostate
      tissue, and a selection of other (nonprostate) normal human tissues, led to the
      identification of a set of clones that were judged as the best candidate markers
      of normal and/or malignant prostate tissue. DNA sequencing of the selected clones
      revealed that they included 10 genes that had previously been established as
      prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 (PSMA), STEAP2, PSGR, PRAC,
      RDH11, Prostein and FASN. Following analysis of the expression patterns of all
      selected and sequenced genes through interrogation of SAGE databases, a further
      three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional
      candidate markers of human prostate cancer. Quantitative RT-PCR demonstrated the
      specificity of expression of HOXB13 in prostate tissue and revealed its
      ubiquitous expression in a series of 37 primary prostate cancers and 20 normal
      prostates. These results demonstrate the utility of this expression-microarray
      approach in hunting for new markers of individual human cancer types.

PMID- 15583693
TI  - Pooled peptides from HER-2/neu-overexpressing primary ovarian tumours induce CTL
      with potent antitumour responses in vitro and in vivo.
AB  - Unfractionated peptides (MW: up to 10 kDa), derived from HLA-A2.1 positive (+)
      HER-2/neu-overexpressing primary tumour cell acid cell extracts (ACE), were
      successfully used to generate in vitro cytotoxic T lymphocytes (CTL). Primary
      tumour cells were collected from peritoneal malignant effusions of patients with
      ovarian cancer. Acid cell extracts-induced CTL specifically lysed in an HLA-A2
      restricted manner HER-2/neu+ autologous primary tumour cells as well as HER
      2/neu+ tumour cell lines. In addition, adoptive transfer of such CTL
      significantly prolonged the survival of SCID mice xenografted with HLA-A2.1+, HER
      2/neu+ human breast and ovarian tumour cell lines. Acid cell extracts collected
      from HLA-A2.1+ HER-2/neu negative (-) primary ovarian tumours induced HLA-A2.1
      restricted CTL with weak in vitro and in vivo antitumour capacity, suggesting
      that HER-2/neu peptides within ACE from HER-2/neu-overexpressing primary ovarian
      tumour cells are immunodominant. The results presented herein serve as a
      rationale for the initiation of vaccination studies in patients with HER-2/neu
      overexpressing ovarian tumours utilising autologous tumour-derived ACE.

PMID- 15583694
TI  - Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated
      repression of androgen receptor signalling.
AB  - Although ErbB receptors have been implicated in the progression of prostate
      cancer, little is known about proteins that may mediate their interactions with
      the androgen receptor (AR). Ebp1, a protein cloned via its association with the
      ErbB3 receptor, binds the AR and inhibits androgen-regulated transactivation of
      wild-type AR in COS cells. As the complement of coregulators in different cells
      are important for AR activity, we determined the effect of Ebp1 on AR function in
      prostate cancer cell lines. In addition, we examined the regulation of Ebp1
      function by the ErbB3/4 ligand heregulin (HRG). In this study, we demonstrate,
      using several natural AR-regulated promoters, that Ebp1 repressed transcriptional
      activation of wild-type AR in prostate cancer cell lines. Downregulation of Ebp1
      expression in LNCaP cells using siRNA resulted in activation of AR in the absence
      of androgen. Ebp1 associated with ErbB3 in LNCaP cells in the absence of HRG, but
      HRG induced the dissociation of Ebp1 from ErbB3. In contrast, HRG treatment
      enhanced both the association of Ebp1 with AR and also the ability of Ebp1 to
      repress AR transactivation. These studies suggest that Ebp1 is an AR corepressor
      whose biological activity can be regulated by the ErbB3 ligand, HRG.

PMID- 15583695
TI  - Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian
      carcinoma.
AB  - KIT and PDGFRA are receptor tyrosine kinases that can be specifically inactivated
      by small-molecule tyrosine kinase inhibitors, notably imatinib mesylate. In
      ovarian carcinoma, expression of KIT and PDGFRA protein has been documented, but
      the frequency and the molecular background of expression are poorly known. We
      analysed the expression of KIT and PDGFRA by immunohistochemistry in 522 serous
      ovarian carcinomas, and mutations of KIT and PDGFRA by denaturing high
      performance liquid chromatographyin 125 and 187 serous ovarian carcinomas,
      respectively. No mutations of KIT or PDGFRA were detected. KIT expression was
      detected in 12% of carcinomas: low expression in 10% and high expression in 2% of
      cases. Using normal serous epithelium as a reference, decreased PDGFRA expression
      was detected in 12% and increased expression in 13% of carcinomas. Both KIT and
      PDGFRA expression were associated with high tumour grade, high proliferation
      index and poor patient outcome. By fluorescence in situ hybridisation, no KIT
      amplification was found in carcinomas with high KIT expression, but two cases
      showed a relative gain of chromosome 4. In conclusion, no mutations of KIT or
      PDGFRA were found, but a subset of serous ovarian carcinoma showed overexpression
      of the proteins, which was associated with aggressive tumour characteristics.

PMID- 15583696
TI  - Expression of HER3, HER4 and their ligand heregulin-4 is associated with better
      survival in bladder cancer patients.
AB  - The epidermal growth factor system has been associated to prognosis in patients
      with bladder cancer based mainly on the expression of the epidermal growth factor
      (EGF) receptor 1 (EGFR) and HER2 and their activating ligands. Since limited
      information exists concerning the expression of other parts of the EGF system, we
      examined the expression of the receptors HER3 and HER4 and their activating
      ligands, the heregulins (HRGs), in bladder cancer patients. Biopsies from bladder
      cancer tumours were obtained from 88 patients followed for a median of 23 months
      (range, 1-97 months). The mRNA content of four ligands and their isoforms
      (HRG1alpha, HRG1beta, HRG2alpha, HRG2beta, HRG3 and HRG4) and two receptors (HER3
      and HER4) was quantified by real-time PCR. A significantly lower mRNA expression
      level of HER3 (P=0.0003), HRG2alpha (P=0.0159), HRG2beta (P=0.0007) and HRG4
      (P<0.0001) was observed in muscle-invasive (T2-T4) tumours as compared to
      superficial (Ta) tumours. The expression of HER3 mRNA correlated strongly to
      overall survival (P=0.0042); increased expression of HER4 (P=0.0261) and HRG4
      (P=0.0245) was also associated with better prognosis. Interestingly, patients
      with coexpression of HER3 (P=0.0034) or HER4 (P=0.0080) together with their
      stimulating ligand HRG4 showed even better survival than for HER3 or HER4 alone.
      Our results together with previous data suggest a dual face for the EGF system.
      While it is well established that an increased signalling through HER1 and HER2
      is related to a poor prognosis, our data suggest that signalling through HER3 and
      HER4 is related to a favourable outcome in bladder cancer patients.

PMID- 15583697
TI  - Enhanced expression of peroxisome proliferator-activated receptor gamma in
      epithelial ovarian carcinoma.
AB  - The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of
      nuclear hormone receptor that executes important cellular transcriptional
      functions. Previous studies have demonstrated the expression of PPARgamma in
      several tumours including colon, breast, bladder, prostate, lung and stomach.
      This study demonstrates the relative expression of PPARgamma in normal ovaries
      and different pathological grades of ovarian tumours of serous, mucinous,
      endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens
      including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and
      12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARgamma was
      not expressed in normal ovaries. Out of eight benign and 10 borderline tumours,
      only one tumour in each group showed weak cytoplasmic PPARgamma expression. In
      contrast, 26 out of 28 carcinomas studied were positive for PPARgamma expression
      with staining confined to cytoplasmic and nuclear regions. An altered staining
      pattern of PPARgamma was observed in high-grade ovarian tumours with PPARgamma
      being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On
      the other hand, predominant cytoplasmic staining was observed in lower-grade
      tumours. Significantly increased PPARgamma immunoreactivity was observed in
      malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline
      tumours (chi2 = 48.80, P < 0.001). Western blot analyses showed significant
      elevation in the expression of immunoreactive PPARgamma in grade 3 ovarian
      tumours compared with that of normal ovaries and benign ovarian tumours (P <
      0.01). These findings suggest an involvement of PPARgamma in the onset and
      development of ovarian carcinoma and provide an insight into the regulation of
      this molecule in the progression of the disease.

PMID- 15583698
TI  - Freiburg Intervention Trial for Obese Children (FITOC): results of a clinical
      observation study.
AB  - BACKGROUND: The Freiburg Intervention Trial for Obese Children (FITOC) is an
      interdisciplinary, outpatient program for obese children consisting of regular
      physical exercise and comprehensive dietary and behavioral education. Parental
      involvement is required. The study is designed as a longitudinal, nonrandomized
      clinical observation study. An 8-month intensive phase preceded a follow-up phase
      of 1 y or longer. METHODS: Data were collected from 31 groups comprising 496
      children (267 girls, 229 boys), with an average age of 10.5 y. Body height and
      weight, fasting total-cholesterol (CH), low-density lipoprotein-cholesterol (LDL
      C), high-density lipoprotein-cholesterol (HDL-C) and physical performance were
      measured initially and after 8.5 months. A group of n = 35 obese children (16
      girls, 19 boys) who did not take part in this intervention program served as
      controls. RESULTS: After the intensive intervention phase, body mass index (BMI,
      kg/m2) as well as BMI deviation scores (BMI-SDS) decreased in both sexes
      (P<0.001). In the controls, BMI increased (P<0.001) and BMI-SDS remained
      constant. Whereas CH was only significantly lower (P<0.01) in boys after 8.5
      months, LDL-C decreased significantly in both sexes. HDL-C tended to increase in
      both sexes (not significant). The controls showed no significant changes in CH,
      LDL-C and HDL-C. The fitness levels (W/kg body weight) improved in the
      intervention group (P<0.001), but not in the control group. CONCLUSIONS: The
      results indicate that obese children can be successfully treated in such an
      intervention program. BMI-SDS and risk factors decreased and physical performance
      improved. To maintain therapeutical success, we highly recommended that these
      children enroll in community-based exercise programs in order to help them
      maintain a more active lifestyle after the follow-up phase.

PMID- 15583699
TI  - Perceptions of local neighbourhood environments and their relationship to
      childhood overweight and obesity.
AB  - OBJECTIVES: To examine associations between parent and child perceptions of the
      local neighbourhood and overweight/obesity among children aged 5-6 and 10-12 y.
      DESIGN: Cross-sectional survey. SUBJECTS: In total, 291 families of 5-6-y-old and
      919 families of 10-12-y-old children. MEASURES: Parent's perceptions of local
      neighbourhood and perceived child access to eight local destinations within
      walking distance of home; 10-12-y-old children's perception of local
      neighbourhood; socio-demographic characteristics (survey). Children's height and
      weight (measured). RESULTS: No perceptions of the local neighbourhood were
      associated with weight status among 5-6-y-old children. Among 10-12-y-old
      children, those whose parents agreed that there was heavy traffic in their local
      streets were more likely to be overweight or obese (OR=1.4, 95% CI=1.0-1.8), and
      those whose parents agreed that road safety was a concern were more likely to be
      obese (OR=3.9, 95% CI=1.0-15.2), compared to those whose parents disagreed with
      these statements. CONCLUSIONS: This study suggests that parental perceptions of
      heavy traffic on local streets and concern about road safety may be indirect
      influences on overweight and obesity among 10-12-y-old children. Future work
      should also consider perceptions of the neighbourhood related to food choice.

PMID- 15583700
TI  - Psychobehavioral and nutritional predictors of weight loss in obese women treated
      with sibutramine.
AB  - OBJECTIVE: To reveal whether baseline body mass index (BMI), and psychobehavioral
      and nutritional markers were significant predictors of the change in BMI observed
      after 4 and 12 months in obese women enrolled in a weight reduction program,
      including low-energy diet, increased physical activity, cognitive behavior
      therapy and sibutramine. The impact of changes in psychobehavioral and
      nutritional markers observed after 4 and 12 months of treatment on BMI changes
      was also investigated. DESIGN: During a double-blind placebo-controlled 4-month
      period, subjects received either sibutramine (10 mg/day) or placebo. Then, an
      open phase with sibutramine administered to all patients continued until month
      12. SUBJECTS: In total, 80 obese women (age: 43.9+/-10.6 y, BMI: 36.7+/-4.8
      kg/m(2)). MEASUREMENTS: The dependent variable was change in BMI while baseline
      BMI, mode of treatment, the Beck depression score, the three items (dietary
      restraint, disinhibition and perceived hunger) of the Eating Inventory (EI),
      energy and macronutrient intakes were independent variables. At 1-week dietary
      records were analyzed using a computer software for assessing energy and
      macronutrient intake. RESULTS: Multiple regression analysis revealed that the BMI
      loss at month 4 was significantly influenced by mode of treatment and initial
      BMI, whereas a borderline negative relationship was observed with the baseline
      restraint score. Baseline BMI, depression score, restraint score and total energy
      intake predicted weight loss at month 12. These predictive variables accounted
      for 43.8% of the variance in BMI loss at 12 months. When relationships between
      the BMI loss and changes in all included psychobehavioral and nutritional
      parameters were considered after 12 months of treatment, a drop in the
      disinhibition score of the EI appeared the only significant factor affecting the
      BMI decrease. CONCLUSIONS: Our results suggest that psychobehavioral and
      nutritional characteristics can be used as predictors of weight loss in response
      to a comprehensive weight management program including pharmacological treatment
      with sibutramine.

PMID- 15583701
TI  - Genetic susceptibility to substance dependence.
AB  - Despite what is often believed, the majority of those who experiment with
      substances with a dependence potential do not develop dependence. However, there
      is a subpopulation of users that easily becomes dependent on substances, and
      these individuals exhibit pre-existing comorbid traits, including novelty seeking
      and antisocial behavior. There appears to be a genetic basis for the
      susceptibility to dependence and these comorbid traits. Animal studies have
      identified specific genes that can alter susceptibility to dependence and
      response to novelty. The mechanisms underlying the genetic susceptibility to
      dependence and response to novelty are complex, but genetic susceptibility plays
      a significant role in the transition from substance use to dependence and from
      chronic use to addiction. We discuss two models to explain how genetic variations
      alter dependence susceptibility. Identification of the specific genes involved in
      these processes would help to identify individuals that are vulnerable to
      dependence/addiction and to devise novel treatment strategies.

PMID- 15583702
TI  - Association between COMT (Val158Met) functional polymorphism and early onset in
      patients with major depressive disorder in a European multicenter genetic
      association study.
AB  - The available data from preclinical and pharmacological studies on the role of
      the C-O-methyl transferase (COMT) support the hypothesis that abnormal
      catecholamine transmission has been implicated in the pathogenesis of mood
      disorders (MD). We examined the relationship of a common functional polymorphism
      (Val108/158Met) in the COMT gene, which accounts for four-fold variation in
      enzyme activity, with 'early-onset' (EO) forms (less than or equal to 25 years)
      of MD, including patients with major depressive disorder (EO-MDD) and bipolar
      patients (EO-BPD), in a European multicenter case-control sample. Our sample
      includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An
      association was found between the high-activity COMT Val allele, particularly the
      COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val
      genotype may be involved in EO-MDD or may be in linkage disequilibrium with a
      different causative polymorphism in the vicinity. The COMT gene may have complex
      and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric
      disorders.

PMID- 15583703
TI  - Reelin glycoprotein: structure, biology and roles in health and disease.
AB  - Reelin glycoprotein is a secretory serine protease with dual roles in mammalian
      brain: embryologically, it guides neurons and radial glial cells to their
      corrected positions in the developing brain; in adult brain, Reelin is involved
      in a signaling pathway which underlies neurotransmission, memory formation and
      synaptic plasticity. Disruption of Reelin signaling pathway by mutations and
      selective hypermethylation of the Reln gene promoter or following various pre- or
      postnatal insults may lead to cognitive deficits present in neuropsychiatric
      disorders like autism or schizophrenia.

PMID- 15583704
TI  - Salvage cryosurgery for locally recurrent prostate cancer following radiotherapy.
AB  - The popularity of radiotherapy as a minimally invasive treatment for prostate
      cancer is increasing. Despite advancements in radiation delivery, a number of
      patients will fail treatment. Salvage radical prostatectomy has been the main
      therapeutic option for locally recurrent radiation failure prostate cancer with
      curative intent. The operation is technically difficult to perform and associated
      with significant comorbidities. Salvage cryotherapy has emerged as a minimally
      invasive alternative option. In this article, we review the role of cryotherapy
      in recurrent prostate cancer and compare its outcome with salvage radical
      prostatectomy.

PMID- 15583705
TI  - Indicators of psychological distress in postacute spinal cord injured
      individuals.
AB  - STUDY DESIGN: Consecutive inclusion of spinal cord injured patients admitted for
      postacute rehabilitation from June 2000 to January 2002. OBJECTIVE: Assessment of
      prevalence of indicators of psychological distress in the subacute and early
      chronic stages after acute-onset spinal cord injury (SCI). SETTING: A Swedish
      rehabilitation center. METHODS: In all, 36 patients participated. Psychological
      assessment was obtained at admission, discharge and 6 months follow-up by
      psychological measures based on the DSM-IV (ie Beck's Depression Inventory,
      SPIFA, SCID-screen, AUDIT) and clinical interview. Ongoing psychotropic
      medication was noted. RESULTS: Clinical depression was infrequent. However,
      ongoing psychotropic medication was common, possibly indicating a relatively high
      incidence of underlying depressive and anxiety disorders. In all, 25% of the
      sample showed indicators of high alcohol consumption. Few patients had a
      previously diagnosed personality disorder. By contrast, there was frequent
      occurrence of personality traits outside normal ranges. CONCLUSION: Medication of
      psychological problems commonly occurs after SCI, especially for depression and
      anxiety. There are indications of alcohol overconsumption in a substantial
      minority of SCI patients. The study raises the question of whether suppression of
      psychological symptoms by drug therapy is the optimal treatment of such problems
      in a rehabilitation process.

PMID- 15583706
TI  - Lipid profiles are influenced by arm cranking exercise and training in
      individuals with spinal cord injury.
AB  - STUDY DESIGN: A prospective, two-group comparative intervention study. OBJECTIVE:
      To determine the acute and training effects of arm cranking exercise on blood
      lipid profiles in wheel chair bound individuals with spinal cord injury (SCI) and
      normal able-bodied subjects. SETTING: Faculty of Science, School of Sport and
      Exercise Science, Liverpool John Moores University, England. METHODS: Total
      cholesterol, triglyceride and high-density lipoprotein cholesterol (HDL-C) at
      rest and in response to arm cranking exercise before and after 12 weeks of
      training were compared between individuals with SCI (N = 5) and able-bodied
      subjects (N = 7). Following the determination of peak oxygen consumption
      (VO2peak), all subjects performed a submaximal arm cranking exercise at an
      intensity corresponding to 60-65% VO2peak for 30 min. Venous blood samples were
      obtained before and after submaximal exercise and measured for total cholesterol,
      triglycerides and HDL-C concentrations. These lipid parameters were remeasured in
      all subjects at rest and in response to the same submaximal arm cranking exercise
      after 12 weeks of individually supervised arm cranking training programme.
      RESULTS: Before training, the resting mean value of triglyceride in individuals
      with SCI was significantly (P < 0.05) higher than that found in able-bodied
      persons. Acute arm cranking exercise did not change total cholesterol or
      triglyceride concentrations in either the SCI or the able-bodied groups. However,
      HDL-C increased significantly following exercise in the able-bodied subjects.
      Following training, the resting mean value of total cholesterol in the group with
      SCI was significantly (P < 0.05) higher compared with able-bodied individuals.
      Furthermore, the resting and post submaximal arm cranking exercise mean values of
      total cholesterol in the able-bodied group, but not in the group with SCI, were
      significantly lower than those observed before training. While the resting mean
      value of HDL-C before training in the group with SCI was lower than that found in
      the able-bodied, this difference did not reach the designated level of
      significance (P > 0.05). Submaximal arm cranking exercise was followed by a
      significant increase in HDL-C only in the able-bodied individuals. Compared to
      pretraining, the resting and post arm cranking exercise levels of HDL-C in the
      group with SCI increased significantly (P < 0.05) after training. CONCLUSION: It
      is concluded that acute arm cranking exercise and training in individuals with
      SCI is associated with favourable effects on HDL-C, whereas total cholesterols
      and triglycerides were not altered. The mechanism responsible for the increase in
      HDL-C with training in individuals with SCI is not known, but it is likely to be
      related to increased activity of cholesterol transport enzymes lipoprotein lipase
      and acyltransferase.

PMID- 15583707
TI  - Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient
      with multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome).
AB  - STUDY DESIGN: Case report of a severe upper cervical cord compression and
      tetraparesis by a massive cervical exostotic osteochondroma in a patient with
      multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome; LGS).
      OBJECTIVE: To describe this very rare pathological condition and the results of
      surgical intervention. SETTING: Gifu, Japan. METHODS: A 23-year-old man was
      referred to our clinic because of progressing tetraparesis. He had previously
      been diagnosed with hereditary multiple exostoses and mental retardation. As he
      had not complained of any symptoms, his family only noticed the tetraparesis
      after advanced deterioration. His face possessed the pathognomic features of LGS.
      A postmyelogram CT scan demonstrated an exostotic mass arising from the left-side
      C2 pedicle with associated severe spinal cord compression. He was diagnosed with
      LGS. Hemilaminectomy on the left side and resection of the osteochondroma were
      performed. RESULTS: At 5 years postoperatively, a neurological examination showed
      the full return of all motor functions. The CT scan revealed no intracanalar
      recurrence of the tumor. CONCLUSION: In this case of severe tetraparesis due to
      cervical osteochondroma, decompression by hemilaminectomy provided excellent
      results. In patients with LGS and intracanalar osteochondroma, the neurological
      deficit may be masked by mental retardation. Hence, awareness of this
      pathological condition will help clinicians diagnose it at an early stage.

PMID- 15583708
TI  - [Training of professionals in the prevention field: current aspects and
      perspectives].

PMID- 15583709
TI  - [Measurement of sulfhemoglobin (S-Hb) blood levels to determine individual
      hydrogen sulfide exposure in thermal baths in Italy].
AB  - Significant exposure to hydrogen sulfide may occur in workers at sulphureous
      thermal baths. Work-related exposure to hydrogen sulfide may be shown by
      measuring sulfhemoglobin (S-Hb) blood levels. In this study we measured S-Hb
      blood levels in two groups of workers at two different thermal baths and compared
      these with hydrogen sulfide concentrations in the air of the two work
      environments. Our results show that blood S-Hb levels can be considered a
      reliable measure of individual exposure to hydrogen sulfide.

PMID- 15583710
TI  - [Results of a study on formaldehyde pollution as a cause of discomfort in public
      sector office workers].
AB  - Medical surveillance of Catania public sector employees who use video display
      terminals (VDTs) revealed complaints of eye and upper respiratory tract
      irritation, skin rash, headache, mental fatigue and reduced concentration in some
      of the workers. These were employed in three recently renovated offices and
      showed the above symptoms while at work. Investigations were performed to verify
      whether contaminants that may cause the above symptoms were present in the indoor
      air. In particular, levels of formaldehyde and CO2 were continuously monitored.
      CO2 levels were found to be higher in offices open to the general public as
      compared to other offices (including the three renovated ones). However, CO2
      levels were never above 1,000 ppm. Formaldehyde was found in the indoor air of
      all three renovated offices in approximately equal concentrations, ranging from a
      minimum of 0,07 - 0,09 ppm to a maximum of 0,3 -0,4 ppm. In addition, a strong
      pungent odor typical of this substance was present in all three renovated offices
      but not in the others. Formaldehyde pollution must always be considered and
      assessed whenever new furnishings that may have required the use of glues that
      emit formaldehyde are brought into an indoor environment.

PMID- 15583711
TI  - [Infection control in dental health care settings: results of a survey on current
      disinfection practices].
AB  - This study was performed to identify which disinfection procedures are currently
      used in dental offices and to evaluate staff knowledge regarding infection
      control. Information was collected by means of a questionnaire to which 226
      subjects responded. Glutaraldehyde was found to be the most commonly used
      disinfectant for surfaces/drill units, handpieces and instruments; however, half
      of the respondents did not specify which disinfectants they used. Eighty-four
      percent of the respondents reported contact times, which in some cases were found
      to be insufficient; 43,4% stated that containers are washed and disinfected each
      time the disinfectant is replaced; 58.8% reported that dental handpieces and
      instruments are precleaned prior to sterilization while 73% believe that
      increased attention during performance of work practices could reduce the risk of
      infection. These findings suggest that dental health care personnel need to be
      better sensitized toward infection control measures and should be offered
      periodical training on the proper implementation of practice guidelines.

PMID- 15583712
TI  - [A retrospective study to evaluate the quality of medical charts and discharge
      abstracts in several Rome hospitals].
AB  - Previous studies have shown that the quality of medical records is not uniform
      across Italian hospitals. Between March 2002 and January 2003, we assessed the
      quality of 6,215 medical charts regarding admissions to 11 different Rome
      hospitals in the year 2001. The hospitals were located within the territory of
      the ROMA "A" and ROMA "C" Local Health Units. The following were evaluated: 1)
      organization, format and lay-out of medical records; 2) medical chart and
      discharge abstract compilation; 3) ICD-9-CM coding accuracy. The quality of
      medical records and of discharge abstracts, as judged especially by their format
      and by the completeness, accuracy, congruency and clearness of the reported
      information, varied extensively among the different wards and hospitals. The main
      problems were identified and possible solutions are discussed. We suggest that
      improved quality of medical records and discharge abstracts may be promoted
      through: 1) use of a standardized format for medical records in all wards of the
      same hospital; a supplement may eventually account for the characteristic
      requirements of specialist wards; 2) adoption of guidelines for medical record
      keeping and of a code of conduct for discharge abstract coders; 3) use of a new
      discharge abstract form that favours more accurate ICD-9-CM coding and that
      allows more effective gathering of clinical data for epidemiological purposes.

PMID- 15583713
TI  - [Health in indoor settings: old and new risks].
AB  - Improved socio-economic and cultural conditions in industrialized countries have
      brought public health workers to focus greater attention to the comfort
      conditions of indoor settings, where people spend as much as 90% of their time.
      This study examines the interaction between man and the indoor environment and
      highlights conditions that may pose health risks in the workplace and home
      because of the presence of chemical, physical, and/or biological pollutants.
      Achieving healthy indoor air quality currently represents a challenge for
      international health organizations, governments and citizens alike.

PMID- 15583714
TI  - [Most important "cost-driver" of the sanitary costs: considerations and
      perspectives].

PMID- 15583715
TI  - Algorithmic self-assembly of DNA Sierpinski triangles.
AB  - Algorithms and information, fundamental to technological and biological
      organization, are also an essential aspect of many elementary physical phenomena,
      such as molecular self-assembly. Here we report the molecular realization, using
      two-dimensional self-assembly of DNA tiles, of a cellular automaton whose update
      rule computes the binary function XOR and thus fabricates a fractal pattern--a
      Sierpinski triangle--as it grows. To achieve this, abstract tiles were translated
      into DNA tiles based on double-crossover motifs. Serving as input for the
      computation, long single-stranded DNA molecules were used to nucleate growth of
      tiles into algorithmic crystals. For both of two independent molecular
      realizations, atomic force microscopy revealed recognizable Sierpinski triangles
      containing 100-200 correct tiles. Error rates during assembly appear to range
      from 1% to 10%. Although imperfect, the growth of Sierpinski triangles
      demonstrates all the necessary mechanisms for the molecular implementation of
      arbitrary cellular automata. This shows that engineered DNA self-assembly can be
      treated as a Turing-universal biomolecular system, capable of implementing any
      desired algorithm for computation or construction tasks.

PMID- 15583719
TI  - Antithrombin extends its job.

PMID- 15583720
TI  - Pharmacotherapy in cardiovascular diseases and vascular interventions.

PMID- 15583716
TI  - Phylogeography and genetic ancestry of tigers (Panthera tigris).
AB  - Eight traditional subspecies of tiger (Panthera tigris),of which three recently
      became extinct, are commonly recognized on the basis of geographic isolation and
      morphological characteristics. To investigate the species' evolutionary history
      and to establish objective methods for subspecies recognition, voucher specimens
      of blood, skin, hair, and/or skin biopsies from 134 tigers with verified
      geographic origins or heritage across the whole distribution range were examined
      for three molecular markers: (1) 4.0 kb of mitochondrial DNA (mtDNA) sequence;
      (2) allele variation in the nuclear major histocompatibility complex class II DRB
      gene; and (3) composite nuclear microsatellite genotypes based on 30 loci.
      Relatively low genetic variation with mtDNA,DRB,and microsatellite loci was
      found, but significant population subdivision was nonetheless apparent among five
      living subspecies. In addition, a distinct partition of the Indochinese
      subspecies P. t. corbetti in to northern Indochinese and Malayan Peninsula
      populations was discovered. Population genetic structure would suggest
      recognition of six taxonomic units or subspecies: (1) Amur tiger P. t. altaica;
      (2) northern Indochinese tiger P. t. corbetti; (3) South China tiger P. t.
      amoyensis; (4) Malayan tiger P. t. jacksoni, named for the tiger conservationist
      Peter Jackson; (5) Sumatran tiger P. t. sumatrae; and (6) Bengal tiger P. t.
      tigris. The proposed South China tiger lineage is tentative due to limited
      sampling. The age of the most recent common ancestor for tiger mtDNA was
      estimated to be 72,000-108,000 y, relatively younger than some other Panthera
      species. A combination of population expansions, reduced gene flow, and genetic
      drift following the last genetic diminution, and the recent anthropogenic range
      contraction, have led to the distinct genetic partitions. These results provide
      an explicit basis for subspecies recognition and will lead to the improved
      management and conservation of these recently isolated but distinct geographic
      populations of tigers.

PMID- 15583721
TI  - Aspirin and coronary artery disease.
AB  - Coronary atherosclerosis (CAD), a chronic inflammatory disorder, arises when
      genetic susceptibility, intercurrent conditions such as diabetes and hypertension
      and environmental factors interact. Although CAD can remain stable for many
      years, thrombus formation at sites of plaque rupture may lead to unstable angina
      (UA) or myocardial infarction (MI). Already recognised as the central component
      of coronary thrombosis, platelets, through their interaction with monocytes and
      endothelial cells, may also be involved at the earliest stages of atheromatous
      plaque evolution. Aspirin, the prototype antiplatelet agent, covalently and
      irreversibly inhibits cyclooxygenase (COX) and thus inhibits platelet thromboxane
      (TX) A(2) biosynthesis. Anti-oxidant properties and the ability to modulate
      transcription of immunologically important genes have also been attributed to
      aspirin. Non-selective COX inhibition, however, predisposes to bleeding,
      predominantly secondary to dosedependent gastro-intestinal toxicity. The emerging
      concept of "aspirin resistance" coincides with the development of alternative
      antiplatelet therapy and point-of-care platelet function assays. Though variable
      aspirin pharmacokinetics may explain many cases, heritable factors, inducible
      platelet COX expression and isoprostane formation may also contribute. In future,
      risk factor screening and point-of-care platelet function assay may identify
      vulnerable patients who would benefit from additional or alternate antiplatelet
      therapy.

PMID- 15583722
TI  - Development of DX-9065a, a novel direct factor Xa antagonist, in cardiovascular
      disease.
AB  - The development of anticoagulants for treating patients with atherothrombotic
      disorders of the arterial circulatory system has focused, either directly or
      indirectly, on thrombin - a pleuripotential effector enzyme with prothrombotic
      and proinflammatory properties. The pivotal role of factor (f) Xa in thrombin
      generation, coupled with its direct cellular effects and widely recognized
      limitations of currently available anticoagulants, has led to the development of
      pharmacologic inhibitors of this important protease. The following review focuses
      on DX-9065a - first in a class of direct, selective and reversible fXa
      antagonists - and its potential applications in the management of patients with
      cardiovascular disease.

PMID- 15583723
TI  - A marriage of enhancement: fibrinolysis and conjunctive therapy.
AB  - Pharmacologic reperfusion of patients with acute ST segment elevation myocardial
      infarction is designed to achieve prompt high-quality reperfusion, prevent
      recurrent ischemia and reinfarction, maintain long-term patency, and to enhance
      patient survival and quality of life. Because monotherapy with fibrinolytics is
      by itself unable to achieve all of these objectives, antithrombotic, anti
      platelet, and other novel agents are required. We discuss herein the role of
      unfractionated and enoxaparin, the potential added value of direct thrombin
      inhibitors, and the importance of aspirin. Despite the promise of glycoprotein
      IIb/IIIa inhibitors, risks associated with intracranial hemorrhage in the elderly
      have led to restraint in their application to broad populations. Facilitation of
      urgent percutaneous coronary intervention with combination reduced-dose
      fibrinolytic and glycoprotein IIb/IIIa inhibitors remains a promising potential
      future path. The future is likely to emphasize greater application of the already
      effective therapies at our disposal and the development of novel anti-platelet
      and anti-thrombin agents as well as those directed toward inflammation.

PMID- 15583724
TI  - Variable extent of clopidogrel responsiveness in patients after coronary
      stenting.
AB  - Clopidogrel is an effective and specific inhibitor of ADP-induced platelet
      aggregation. After metabolic activation, the active clopidogrel metabolite
      irreversibly impairs the human platelet P2Y12 ADP receptor. Gialpha-protein
      activation and inhibition of vasodilator-stimulated phosphoprotein (VASP)
      phosphorylation are two key elements of the P2Y12 receptor pathway suitable for
      quantitation of clopidogrel effects. So far, only limited data exist about a
      diminished responsiveness to clopidogrel and underlying possible mechanisms. We
      investigated clopidogrel effects in 57 patients after percutaneous coronary
      intervention and stent implantation by flow cytometry for the analysis of
      intracellular VASP phosphorylation. Patients were treated with a 300 mg
      clopidogrel loading dose, followed by 75 mg/day clopidogrel in combination with
      100 mg/day aspirin. Samples were drawn after a median of 5 days of clopidogrel
      treatment. Considerable differences in the responsiveness to clopidogrel could be
      observed and it was shown that 17.5% (10/57) of the patients revealed an
      inadequate responsiveness to clopidogrel despite continuation of clopidogrel
      intake. Comparable amounts of Gialpha and VASP were found in two clopidogrel low
      responding patients as well as in two responding patients. To exclude a molecular
      defect of P2Y12 ADP receptor, the P2Y12 receptor gene of eight clopidogrel
      treated patients (seven patients with inadequate responsiveness, one responder)
      was sequenced. We only found a single silent mutation in exon 2 at position 1828
      (GA). We suggest that individual differences in clopidogrel metabolization could
      cause relevant variations in clopidogrel responsiveness despite the use of a 300
      mg clopidogrel loading dose.

PMID- 15583725
TI  - Comparison of two methods to assess variability of platelet response to anti
      platelet therapies in patients with acute coronary syndrome undergoing
      angioplasty.
AB  - The study investigated the clinical usefulness of a new method to evaluate
      platelet activation and the variability of platelet response to anti-platelet
      therapy in patients undergoing percutaneous transluminal coronary angioplasty
      (PTCA). Platelet activation was assessed in parallel by a new method for platelet
      density measurements (MPC, Mean Platelet Component Concentration), on the
      automated ADVIA 120 Hematology System and by the classic measurement of P
      selectin (CD62P) expression, on a fluorescence flow cytometer. Patients received
      a loading dose of clopidogrel (300 mg; n = 29) or a bolus of abciximab (0.25
      mg/kg; n = 15). Blood samples were collected before (baseline) and at different
      times after PTCA and antiplatelet drugs administration. Our data showed a close
      inverse correlation between the change in MPC and the CD62P fluorescence surface
      marker expression (r = -0.776, P<0.0001). Individual platelet activation
      determinations in patients receiving either clopidogrel or abciximab showed a
      variation in platelet activation as assayed by MPC and CD62P expression. Patients
      were characterized as having either high platelet activity upon admission and
      positive response to treatment or no detectable platelet activation before or
      after treatment. This study demonstrates the heterogeneity of platelet activation
      states in ACS patients undergoing coronary angioplasty. The present work also
      illustrates the potential use of the MPC parameter, generated on an automated
      hematology system, to define high risk patients and to monitor the variability of
      platelet response to anti-platelet therapies.

PMID- 15583726
TI  - Admission troponin T, advanced age and male gender identify patients with
      improved myocardial tissue perfusion after abciximab administration for ST
      segment elevation myocardial infarction.
AB  - The aim was to investigate the effect of abciximab on microvascular perfusion in
      different subgroups of patients undergoing direct PCI for acute STEMI. We
      enrolled 145 consecutive patients with TIMI grade 3 flow after direct PCI for
      acute STEMI. The GPIIb/IIIa inhibitor abciximab was administered in 57 patients
      (39.3%). Myocardial perfusion was the primary outcome measure and was assessed by
      analysis of cardiac troponin T wash-out. Treatment effects on myocardial
      perfusion and clinical outcome were tested for predefined subgroups including
      patients with an admission cTnT > or = 0.1 microg/L, diabetes mellitus, male
      gender, age > 70 years, and time from symptom onset to reperfusion > 6 hours. A
      significant improvement of cTnT wash-out was seen in patients with an admission
      cTnT > or = 0.1 microg/L, in males and in older patients. Improved tissue level
      reperfusion did not translate into a significant reduction of cardiac mortality
      or the incidence of the combined endpoint consisting of cardiac death, nonfatal
      reinfarction and need for target vessel revascularisation during 30 day- and long
      term follow-up (mean 274 days). In conclusion, adjunctive administration of
      abciximab improves myocardial perfusion in patients with normal epicardial flow
      after direct PCI, particularly in patients with an cTnT > or = 0.1 microg/L on
      admission, age over 70 years and male gender.

PMID- 15583727
TI  - Combined effects of a factor Xa inhibitor YM466 and a GPIIb/IIIa antagonist YM128
      on thrombosis and neointima formation in mice.
AB  - Thrombosis and neointima formation limit the efficacy of coronary angioplasty.
      Factor Xa inhibitors and GPIIb/IIIa antagonists have shown to be effective on
      acute thrombosis and late neointima formation, however, their combined effects
      remain to be elucidated. Vascular injury was induced by FeCl(3) in the carotid
      artery in mice. For thrombosis studies, the test drug was orally administered 1
      hour before vascular injury. For neointima studies, the test drug was orally
      administered 1 hour before and twice daily for 1 week after vascular injury, and
      then histological analysis was performed 3 weeks after vascular injury. YM466
      inhibited thrombotic occlusion at 30 mg/kg with prolongation of prothrombin time
      (PT), and tail transection bleeding time (BT) was affected at 100 mg/kg. YM466
      also inhibited neointima formation at 10 mg/kg. YM128 inhibited thrombotic
      occlusion and neointima formation at 10 and 30 mg/kg, respectively, with
      inhibition of platelet aggregation and prolongation of BT. In contrast, the
      combination of 10 mg/kg YM466 and 3 mg/kg YM128 inhibited thrombotic occlusion
      and neointima formation without affecting PT, platelet aggregation and BT.
      Concomitant inhibition of factor Xa and GPIIb/IIIa may provide a safer and more
      effective therapeutic regimen for treatment of coronary angioplasty.

PMID- 15583728
TI  - The indazole derivative YD-3 inhibits thrombin-induced vascular smooth muscle
      cell proliferation and attenuates intimal thickening after balloon injury.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) is postulated to be one of
      the key events in the pathogenesis of atherosclerosis and restenosis. We
      investigated whether YD-3, a lowmolecular weight, non-peptide compound, could
      modulate proliferation of VSMCs in vitro and restenosis after balloon angioplasty
      in vivo. We examined the effect of YD-3 on thrombininduced VSMC proliferation by
      [(3)H]thymidine incorporation assay. The data demonstrated that YD-3 inhibited
      VSMC proliferation in a concentration-dependent manner. To define the mechanisms
      of YD-3 action, we found that YD-3 showed a profound inhibition on thrombin
      induced Ras and ERK1/2 activities by using Western blotting analysis.
      Furthermore, oral administration of YD-3 exhibited a marked reduction in
      neointimal thickness using the carotid injury model in rats. Using immunochemical
      detection, our experiments also revealed that YD-3 significantly suppressed
      expression of the PAR-1 receptor, and markedly inhibited PAR-1-activating peptide
      (SFLLRN)-induced VSMC proliferation in a concentration-dependent manner. These
      results suggest that YD-3 inhibits thrombin-induced VSMC growth via the Ras- and
      ERK1/2-mediated signaling pathway. Moreover, YD-3 also shows a developmental
      potential in the treatment of atherosclerosis and restenosis after vascular
      injury.

PMID- 15583729
TI  - Plasma fibrinogen concentration predicts the risk of myocardial infarction
      differently in various parts of Europe: effects of beta-fibrinogen genotype and
      environmental factors. The HIFMECH Study.
AB  - The propensity to atherothrombotic disease differs in Europe, with high-risk
      regions located in the North of Europe and lowrisk regions in the South of
      Europe. The HIFMECH study (Hypercoagulability and Impaired Fibrinolytic function
      MECHanisms predisposing to myocardial infarction (MI) study) was undertaken to
      elucidate genetic and environmental mechanisms underlying MI based on
      investigations of postinfarction patients and healthy individuals recruited from
      Stockholm, Sweden, London, England (North of Europe), Marseille, France and San
      Giovanni Rotondo, Italy (South of Europe). In the present report, emphasis was
      placed on fibrinogen, a multifunctional protein, widely recognized as an
      independent predictor of atherothrombotic disease. The adjusted plasma fibrinogen
      concentration was an independent discriminator between cases and controls in
      London (SOR 3.58; 95% CI 1.31; 9.83), but not in the other centres. Genotyping
      for six beta-fibrinogen promoter single nucleotide polymorphisms was performed of
      which -249C/T, -455G/A and -854G/A were used in analysis as a consequence of the
      linkage disequilibrium pattern. Four haplotypes, with similar distribution across
      Europe, were detected: CGG (46.7%), CAG (20.3%), TGG (18.2%) and CGA (14.8%). A
      significant haplotype effect on plasma fibrinogen concentration was observed in
      patients (p < 0.001) but not in controls (p = 0.08). The -455G/A genotype related
      to plasma fibrinogen concentration amongst patients along with centre and IL-6
      concentration (together explaining 11.5% of the variation), whereas predictors
      amongst controls included centre, body mass index, IL-6 and smoking habit
      (explaining 15.7%). Thus, plasma fibrinogen concentration contributes differently
      to MI across Europe, and a disease-related stimulus is required to evoke allele
      specific regulation of fibrinogen synthesis.

PMID- 15583730
TI  - Elevated D-dimer level is an independent risk factor for cardiovascular death in
      out-patients with symptoms compatible with heart failure.
AB  - D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a
      biological marker of thrombosis. Some of the properties of D-dimer might also be
      used to provide additional information about patients with heart failure. In this
      study, we evaluate the prognostic information acquired from D-dimer concerning
      increased risk of cardiovascular mortality in an elderly population with symptoms
      associated with heart failure. A cardiologist examined 458 elderly patients, out
      of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or
      peripheral oedema and assessed NYHA functional class and cardiac function.
      Abnormal systolic function was defined as EF <40% on Doppler echocardiography.
      Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal
      pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer
      were analysed. D-dimer was analysed using an automated micro-latex assay. A
      statistical analysis was performed to identify the prognostic value of increased
      plasma concentration of D-dimer. Results showed that during a median follow-up
      period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender
      difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the
      risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for
      cardiovascular mortality that may be used to risk-stratify patients with heart
      failure.

PMID- 15583731
TI  - Hepatitis C in haemophiliacs.
AB  - Virtually all haemophiliacs who received non-virucidally treated, large-pool
      clotting factor concentrates before 1986 became infected with hepatitis C virus
      (HCV). Although approximately one-tenth of HCV-infected people have been shown to
      clear the infection naturally, in the remaining cases the infection slowly
      progresses. Unfortunately, a significant percentage of HCV-infected hemophilic
      patients were also co-infected with human immunodeficiency virus (HIV), which can
      accelerate the progression to cirrhosis and liver failure. As regards treatment,
      combination therapy with interferon (IFN) and ribavirin has improved the poor
      results obtained with IFN monotherapy and has become the standard treatment of
      chronic hepatitis C. Given the positive results obtained with pegylated
      interferon in non-haemophiliacs, ongoing trials are evaluating this promising
      therapy in HCV-chronically infected haemophilic patients. Finally, anti-HCV
      treatment should also be considered for those haemophiliacs co-infected with HIV
      in whom anti-retroviral treatment has stabilized the HIV infection.

PMID- 15583732
TI  - Prostaglandin E2 activates channel-mediated calcium entry in human erythrocytes:
      an indication for a blood clot formation supporting process.
AB  - Prostaglandin E(2) (PGE(2)) is released from platelets when they are activated.
      Using fluorescence imaging and the patch-clamp technique, we provide evidence
      that PGE(2) at physiological concentrations (10(-10) M) activates calcium rises
      mediated by calcium influx through a non-selective cation-channel in human red
      blood cells. The extent of calcium increase varied between cells with a total of
      45% of the cells responding. It is well known that calcium increases elicited the
      calcium-activated potassium channel (Gardos channel) in the red cell membrane.
      Previously, it was shown that the Gardos channel activation results in potassium
      efflux and shrinkage of the cells. Therefore, we conclude that the PGE(2)
      responses of red blood cells described here reveal a direct and active
      participation of erythrocytes in blood clot formation.

PMID- 15583733
TI  - Genetic variation in Fcgamma receptor IIa protects against advanced peripheral
      atherosclerosis. The Rotterdam Study.
AB  - Immune processes play a substantial role in atherosclerotic disease. The role in
      atherosclerosis of Fcgamma receptor IIa (FcgammaRIIa), a receptor for
      immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet
      clear. Since the R/H131 polymorphism in the FcgammaRIIa gene strongly influences
      binding to FcgammaRIIa, we investigated the association of the R/H131
      polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam
      Study, a population-based cohort study, we determined FcgammaRIIa genotype in 430
      subjects with advanced peripheral atherosclerosis as indicated by the ankle-arm
      index, and 411 controls. Heterozygous and homozygous carriers of the H131 allele
      were protected against advanced peripheral atherosclerosis (age- and gender
      adjusted odds ratio (OR) 0.77 (0.54-1.12) and 0.65 (0.44-0.98), respectively, P
      trend=0.04). This effect was most pronounced in subjects with modestly elevated
      levels of inflammation as indicated by the leukocyte count (OR 0.52 (0.29-0.93)
      and 0.45 (0.23-0.86), for heterozygotes and H131 homozygotes, respectively; P
      trend=0.02). This is the first study showing that the H131 allele of FcgammaRIIa
      protects against advanced peripheral atherosclerosis.

PMID- 15583734
TI  - Inhibition of plasma kallikrein by C1-inhibitor: role of endothelial cells and
      the amino-terminal domain of C1-inhibitor.
AB  - Activation of plasma prekallikein and generation of bradykinin are responsible
      for the angioedema attacks observed with C1-inhibitor deficiency. Heterozygous
      individuals with <50% levels of active C1-inhibitor are susceptible to angioedema
      attacks indicating a critical need for C1-inhibitor to be present at maximum
      levels to prevent unwanted prekallikrein activation. Studies with purified
      proteins do not adequately explain this observation. Therefore to investigate why
      reduction of C1-inhibitor to levels seen in angioedema patients results in
      excessive kallikrein generation we examined the effect of endothelial cells on
      the inhibition of kallikrein by C1-inhibitor. Surprisingly, it was found that a
      C1-inhibitor concentration of greater than 1 microM was needed to inhibit 3 nM
      kallikrein. We propose that this apparent protection from inhibition was mediated
      by kallikrein binding to the cells via the heavy chain in a high molecular weight
      kininogen and zinc independent manner. Protection of kallikrein from inhibition
      was not observed when C1-inhibitor truncated in the amino-terminal domain by the
      StcE metalloproteinase was used, which suggests a novel function for this unique
      domain. The requirement for high concentrations of C1-inhibitor to fully inhibit
      kallikrein is consistent with the fact that reduced levels of C1-inhibitor result
      in the kallikrein activation seen in angioedema.

PMID- 15583735
TI  - Gradually glycosylated protein C mutants (Arg178Gln and Cys331Arg) are degraded
      by proteasome after mannose trimming.
AB  - Proteins that fail to attain their correct three-dimensional structure are
      retained in the endoplasmic reticulum (ER) and eventually degraded within the
      cells. We investigated the degradation of mutant proteins, using naturally
      occurring protein C (PC) mutants (Arg178Gln and Cys331Arg) which lead to
      congenital deficiencies. Chinese hamster ovary (CHO) cells were transfected with
      normal or mutant expression vectors. The introduction of mutation at Asn329 of an
      unusual sequence Asn-X-Cys for N-linked glycosylation revealed that the mutation
      at Cys331, which may preclude a formation of disulfide bond with Cys345, resulted
      in no addition of N-linked oligosaccharides at Asn329. PC mutants with 4
      glycosylation sites were gradually glycosylated in the ER, and the fourth
      glycosylation site is less accessible for glycosylation as reported for PC in
      plasma. The half lives of PC178 and PC331 mutants were about 5 and 4 h,
      respectively. PC mutants were degraded, but the degradation was inhibited by
      inhibitors for proteasome. Mannose trimming of N-linked oligosaccharides after
      glucose removal targeted PC mutants for degradation by proteasomes. And also the
      inhibition of glucose trimming immediately led to mannose trimming, resulting in
      the accelerated degradation of PC mutants. These degradations were inhibited by
      mannosidase I inhibitor, kifunensine. These results indicate that the initiation
      of mannose trimming by mannosidase I leads to the proteasomemediated degradation
      of glucose-trimmed or untrimmed PC mutants.

PMID- 15583736
TI  - Hypofibrinogenaemia associated with a novel heterozygous gamma289 Ala -->Val
      substitution (fibrinogen Dorfen).
AB  - The molecular basis of hypofibrinogenaemia was investigated in a 34-year-old
      woman and her 10-year-old daughter. DNA sequencing revealed a single heterozygous
      GCC-->GTC transition in exon 8 of the fibrinogen gamma ?gene in both subjects,
      predicting a novel gamma289 Ala-->Val substitution. Examination of fibrinogen
      gamma ?chains by electrospray ionization mass spectrometry failed to detect the
      variant chain in plasma fibrinogen. Further evidence for its non-expression came
      from tryptic peptide mapping. The mutation predicts a mass increase of 28 Da in
      peptide T32, but only the normal (M + 2H) ion was detected at 1418 m/z in the
      proposita. Our finding that gamma289 is an important determinant of plasma
      fibrinogen levels highlights the role of mutational analysis in defining
      structurally important regions of the fibrinogen molecule. This case suggests
      that the highly conserved Ala(289) is important in maintaining structure of the
      "a" polymerization site via hydrogen bonding to Thr(371).

PMID- 15583737
TI  - In vitro comparison of the effect of fondaparinux and enoxaparin on whole blood
      tissue factor-triggered thromboelastography profile.
AB  - Fondaparinux and enoxaparin are both effective and safe in preventing post
      operative venous thromboembolism. However, neither of them significantly
      influence the conventional clotting tests. We compared the influence of
      clinically relevant concentrations of fondaparinux and enoxaparin on normal whole
      blood (WB) thromboelastographic profiles after triggering TF-pathway with minimal
      amount of thromboplastin. Diluted thromboplastin was added to WB samples
      supplemented with buffer (control), fondaparinux (0.25; 0.5; 1 microg/ml), or
      enoxaparin (0.1; 0.5; 1 anti-Xa IU/ml). Four parameters were analyzed, R:
      clotting time, K: time required to reach an amplitude of 20 mm, alpha angle:
      measurement reflecting clot development kinetics and MA: maximal amplitude. At
      concentrations used in prophylaxis, both enoxaparin (0.1 anti-Xa IU/ml) and
      fondaparinux (0.25 microg/ml which correspond to 0.27 anti-Xa IU/ml)
      significantly prolonged the R and K times, but did not significantly modify the
      alpha angle as compared to the control. At concentrations observed after
      administration of curative doses for the treatment of DVT (> or = 0.5 anti-Xa
      IU/ml for enoxaparin and > or = 0.5 microg/ml for fondaparinux) both drugs
      induced a significant increase of R and K times, and a significant decrease of
      the alpha angle (p < 0.05). In contrast to fondaparinux, enoxaparin at
      concentrations equal to or higher than 0.5 anti-Xa IU/ml significantly reduced
      MA. The present study provides evidence that the whole blood TF-triggered TEG
      assay is sensitive to the presence of clinically relevant concentrations of
      enoxaparin or fondaparinux. Moreover, the angle may be used in order to
      distinguish the effect of prophylactic and therapeutic concentrations, since it
      was significantly reduced by the later ones. Further studies are needed to
      evaluate the clinical usefulness of whole blood TF-triggered TEG assay for the
      monitoring of treatment with enoxaparin or fondaparinux.

PMID- 15583738
TI  - Anti-CD40 antibodies in antiphospholipid syndrome and systemic lupus
      erythematosus.
AB  - Anti-beta2glycoprotein I (anti-beta2GPI) antibodies constitute the main
      autoantibody specificity in the sera of patients with antiphospholipid syndrome
      (APS). There is evidence that anti-beta2GPI antibodies induce the precoagulant
      activity of the endothelium by cross-linking the beta2 glycoprotein I (beta2GPI)
      on the cell surface. Since beta2GPI lacks intracellular domains, homology with
      other molecules such as CD40 that could initiate signaling, was extensively
      searched. A 86% homology between the amino acid position 239-245 of the CD40 and
      7-13 of the beta2glycoprotein was found. The CD40 peptide corresponding to amino
      acids 239-245 of the CD40 molecule was synthesized and coupled to a multiple
      antigenic peptide carrier. Antibodies to CD40 peptide were found in 61.5% APS
      patients (n = 39), in 72.7% of systemic lupus erythematosus (SLE) positive for
      anti-beta2GPI antibodies (n = 11) and 31.6% of SLE negative for anti-beta2GPI
      antibodies (n = 19), but not in rheumatoid arthritis patients (n = 28) or
      controls (n = 36). Antibodies to CD40 peptide were associated with arterial
      thrombosis and/or brain microinfarcts. Affinity purified anti-CD40 peptide
      antibodies as well as affinity purified anti-beta2GPI antibodies recognized both,
      the beta2GPI and the CD40 peptide. The specificity of this recognition was
      confirmed with homologous and heterologous inhibition experiments. Confocal
      microscopy experiments demonstrated this cross-recognition of CD40 and beta2GPI
      molecules, by the purified anti-CD40 peptide antibodies, at the protein level.
      Thus, antibodies reacting with the beta2GPI can react and potentially activate
      different cells which express CD40 molecules at their surface.

PMID- 15583739
TI  - Antiphospholipid antibodies and thrombosis: association with acquired activated
      protein C resistance in venous thrombosis and with hyperhomocysteinemia in
      arterial thrombosis.
AB  - Although antiphospholipid antibodies (aPL) are associated with thrombosis, it is
      not known who with aPL is at higher risk for thrombosis. It was the aim of this
      cross-sectional study to investigate how thrombophilic factors contribute to
      venous or arterial thrombosis in aPL-positive individuals. In outpatient test
      centres at two tertiary care hospitals, two hundred and eight (208) persons
      requiring aPL testing were matched by age, gender and centre to 208 persons
      requiring a complete blood count. Persons were classified as aPL-positive (having
      anticardiolipin, lupus anticoagulant and/or anti-beta(2)-glycoprotein I
      antibodies) or aPL-negative. Several thrombophilic factors were studied using
      logistic regression modelling. Results showed that the aPL-positive group had
      three-fold more events (37%) than the aPL-negative group (12%). In unadjusted
      analyses, clinically important associations were observed between factor V Leiden
      and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and
      activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00,
      1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting
      for recruitment group, persons with both APCR and aPL had a three-fold greater
      risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither
      APCR nor aPL. Similarly, after adjusting for hypertension, family history of
      cardiovascular disease, gender and recruitment group, persons with both
      hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90,
      1.37-17.37) for arterial thrombosis compared to those with neither risk factor.
      In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a
      higher risk of venous and arterial thrombosis, respectively, in the presence of
      aPL.

PMID- 15583740
TI  - von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non
      pregnant women, pregnant and post-delivery women.
AB  - ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic
      Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in
      13% of them, is associated with pregnancy. However, there is little information
      on the protease behaviour in normal pregnancy. We studied von Willebrand factor
      and ADAMTS13 activity changes in normal non-pregnant, pregnant and post-delivery
      women. Fifty-five non-pregnant women, normal blood bank donors, who were not
      taking contraceptive pills were included as controls. A prospective cross
      sectional study of 270 normal pregnant and post-delivery women was carried out.
      ADAMTS13 activity decreased progressively as from the period of 12-16 weeks up to
      the end of early puerperium (mean 52%, range 22-89, p < 0.0001), to increase
      slightly thereafter. Nulliparous presented mildly lower levels of ADAMTS13
      activity than parous women (65% vs. 83 %, p = 0.0003), and primigravidae than
      multigravidae between 6-11 weeks up to 17-23 weeks of pregnancy (69% vs. 80%, p =
      0.005). Although in all women the protease levels were the same by blood groups,
      the O blood group non-pregnant women showed a higher mean of ADAMTS13 activity
      than those non-O (78% vs. 69%, p = 0.064). Our results suggest that the changing
      levels of protease activity during pregnancy and puerperium, induced by
      unidentified mechanisms, could render the peripartum time more vulnerable to
      developed thrombotic microangiopathies.

PMID- 15583741
TI  - The effect of natural habituation on coagulation responses to acute mental stress
      and recovery in men.
AB  - Blood coagulation activation might be one mechanism linking acute mental stress
      with coronary events. We investigated the natural habituation of coagulation
      responses and recovery to short-term mental stress. Three times with one-week
      intervals, 24 men (mean age 47 +/- 7 years) underwent the same 13-min stressor
      (preparation, job interview, mental arithmetic). During each visit venous blood
      was obtained four times (baseline, immediately post-stress, 45 min of recovery,
      105 min of recovery). Eight blood coagulation parameters were measured at weeks
      one and three. Acute stress provoked increases in von Willebrand factor antigen,
      fibrinogen, clotting factor FVII activity (FVII:C), FVIII:C, FXII:C (p's < or =
      0.019), and D-dimer (N.S.). All coagulation parameters experienced full recovery
      except FVIII:C (p = 0.022). Stress did not significantly affect activated partial
      thromboplastin time and prothrombin time. At all time points FVIII:C and FXII:C
      levels were significantly higher at week one compared to week three (p's < or =
      0.041). Before catheter insertion, systolic blood pressure (p = 0.001) and heart
      rate (p = 0.026) were relatively higher at week one. Unlike the magnitude of
      systolic blood pressure response to stress (p = 0.007) and of cortisol recovery
      from stress (p = 0.002), the magnitude of all coagulation responses to stress and
      the recovery from stress were similar in week one and week three. Sympathetic
      activation with anticipatory stress best explained increased baseline activity in
      FVIII and FXII at week one. An incapacity of the coagulation system to adapt to
      stress repeats is perhaps a consequence of evolution, but might also contribute
      to increased coronary risk in some individuals, particularly in those with
      cardiovascular diseases.

PMID- 15583742
TI  - Treatment of venous thromboembolism with vitamin K antagonists: patients' health
      state valuations and treatment preferences.
AB  - Determining the optimal duration of vitamin K antagonist (VKA) therapy for
      patients with venous thromboembolism (VTE) requires a weighting of the benefits
      and risks of treatment. The objectives of our study were to investigate patient
      variability in health state valuations associated with VKA therapy and treatment
      preferences, and to investigate the extent to which valuations and treatment
      preferences are associated with prior experience with these health states and
      other patient characteristics. Valuations of outcomes after VTE scaled from 0
      (tantamount to death) to 1 (tantamount to perfect health) were elicited from 53
      patients who had experienced VTE, 23 patients who had experienced major bleeding
      during treatment, and 48 patients with the post-thrombotic syndrome. In addition,
      patients' treatment preferences were evaluated using treatment trade-off
      questions. Median health state valuations ranged from 0.33 for 'non-fatal
      haemorrhagic stroke' to 0.96 for 'no VKA treatment'. Variability between patients
      was substantial. Patients' treatment preferences also varied: 25% of patients
      chose cessation of treatment, regardless of the probability of recurrent VTE
      presented, whereas 23% of patients were never willing to choose cessation of
      treatment. Differences in valuations and treatment preferences were not
      associated with type of event experienced. Due to the substantial and
      unpredictable variability in valuations and treatment preferences,
      recommendations regarding treatment duration should be tailored to patients'
      specific values and concerns.

PMID- 15583743
TI  - Platelet morphology, soluble P selectin and platelet P-selectin in acute
      ischaemic stroke. The West Birmingham Stroke Project.
AB  - The pathophysiology of ischaemic stroke involves the platelet. In this study, we
      hypothesised that abnormalities in platelet morphology, as well as soluble
      (sPsel) and total platelet P-selectin (pPsel) levels would be present in patients
      presenting with an acute ischaemic stroke, and that these changes would improve
      at > or = 3 months' follow-up. We studied 59 hypertensive patients (34 male; mean
      age 68 +/- 12 years) who presented with an acute ischaemic stroke (ictus < 24
      hours), and compared them with 2 groups: (i) age-, sex- and ethnic- origin
      matched normotensive healthy controls; and (ii) uncomplicated 'high risk'
      hypertensive patients as 'risk factor control' subjects. Platelet morphology
      (volume and mass) was quantified, and sPsel (plasma marker of platelet
      activation) was measured (ELISA) in citrated plasma. The mass of P-selectin in
      each platelet (pPsel) was determined by lysing a fixed number of platelets and
      then determining the levels of P-selectin in the lysate. Results show that
      patients who presented with a stroke had significantly higher levels of sPsel and
      pPsel (both p < 0.001), compared to the normal controls and the hypertensive
      patients. Patients with an acute stroke had lower mean platelet mass (MPM) and
      mean platelet volume (MPV) as compared to the uncomplicated hypertensive
      patients, who had significantly higher mean MPM and MPV values, as compared to
      normal controls. On follow-up, the levels of both sPsel (p = 0.011), pPsel (<
      0.001) and MPV (p = 0.03) were significantly lower. Mean MPM levels remained
      unchanged. We conclude that patients presenting with an acute ischaemic stroke
      have activated platelets, as evident by the increased levels of soluble and
      platelet P-selectin. Further study of platelet activation and the role of P
      selectin is warranted.

PMID- 15583744
TI  - Human platelets contain forms of factor V in disulfide-linkage with multimerin.
AB  - Factor V is an essential cofactor for blood coagulation that circulates in
      platelets and plasma. Unlike plasma factor V, platelet factor V is stored
      complexed with the polymeric alpha-granule protein multimerin. In analyses of
      human platelet factor V on nonreduced denaturing multimer gels, we identified
      that approximately 25% was variable in size and migrated larger than single chain
      factor V, the largest form in plasma. Upon reduction, the unusually large,
      variably-sized forms of platelet factor V liberated components that comigrated
      with other forms of platelet factor V, indicating that they contained factor V in
      interchain disulfide-linkages. With thrombin cleavage, factor Va heavy and light
      chain domains, but not B-domains,were liberated from the components linked by
      interchain disulfide bonds, indicating that the single cysteine in the B-domain
      at position 1085 was the site of disulfide linkage. Since unusually large factor
      V had a variable size and included forms larger than factor V dimers, the data
      suggested disulfide-linkage with another platelet protein, possibly multimerin.
      Immunoprecipitation experiments confirmed that unusually large factor V was
      associated with multimerin and it remained associated in 0.5 M salt. Moreover,
      platelets contained a subpopulation of multimerin polymers that resisted
      dissociation from factor V by denaturing detergent and comigrated with unusually
      large platelet factor V, before and after thrombin cleavage. The disulfide-linked
      complexes of multimerin and factor V in platelets, which are cleaved by thrombin
      to liberate factor Va, could be important for modulating the function of platelet
      factor V and its delivery onto activated platelets. Factor Va generation and
      function from unusually large platelet factor V is only speculative at this time.

PMID- 15583745
TI  - Effect of activated platelets on expression of cytokines in peripheral blood
      mononuclear cells - potential role of prostaglandin E2.
AB  - Platelets may act as inflammatory cells. To study the effects of soluble and cell
      bound platelet factors on the expression of several cytokines and related
      mediators in leukocytes, peripheral blood mononuclear cells (PBMC) were incubated
      with platelet-free supernatants from SFLLRN-activated platelet-rich plasma (PRP)
      or SFLLRN-activated PRP in itself. Our main findings were: (i) the gene
      expression of several chemokines and some cytokines were markedly increased by
      both activated PRP and supernatants, as also confirmed at the protein level for
      IL-6, IL-8 and MIP-1alpha; (ii) the selective protein kinase A type I (PKAI)
      antagonist Rp-8-Br-cAMP reduced this platelet-induced expression of IL-6, IL-8
      and MIP-1alpha in PBMC, suggesting a role of cAMP/PKAI mediated mechanisms in
      this interaction; (iii) PGE(2) dose-dependently increased the release of IL-6, IL
      8 and MIP-1alpha from PBMC mimicking the effect of activated platelets.
      Furthermore, activated platelets released comparable amounts of PGE(2),
      suggesting that platelet-derived PGE2 could interact with PBMC in co-cultures;
      (iv) IL-10 inhibited the platelet-inducing effect on IL-6, IL-8 and MIP-1alpha in
      PBMC, and notably, the addition PGE2 totally abolished this IL-10 effect
      suggesting that the suppressive effect of IL-10 on the plateletinduced activation
      of PBMC might at least partly involve PGE(2) related mechanisms. The present
      study supports a view of platelets as inflammatory cells, and suggests a
      potential role of platelet-derived PGE(2) in platelet-induced inflammatory
      responses.

PMID- 15583746
TI  - alpha-Adrenergic-mediated activation of human reconstituted fibrinogen receptor
      (integrin alphaIIbbeta3) in Chinese hamster ovary cells.
AB  - This work reports the functional studies of CHO cells coexpressing alpha
      adrenergic (alphaAR) and human fibrinogen (Fg) receptors (integrin
      alphaIIbbeta3). Stimulation of these cells with alpha-agonists produced a
      transient rise in the free cytosolic calcium (Ca(++)) accompanied by enhanced
      binding to soluble Fg, and these effects were prevented by specific alphaAR
      antagonists. The alpha-adrenergic-induced activation of alphaIIbbeta3 in CHO
      alphaIIbbeta3-alphaAR increased the rate of adhesion and extension of cells onto
      Fg coated plates, and also induced a soluble Fg- and alphaIIbbeta3-dependent
      formation of cell aggregates, whereas no effects were observed by the stimulation
      of CHO-alphaIIbbeta3 cells. alpha-Adrenergic antagonists, the ligand mimetic
      peptide RGDS, pertussis toxin (PTX), or EDTA, they all prevented the alpha
      adrenergic stimulation of adhesion and aggregation. However, inhibition of PKC
      prevented the alpha-adrenergic stimulation of cell adherence, whereas blocking
      the intracellular Ca(++) mobilization impeded the stimulation of cell
      aggregation. The alpha-adrenergic activation was associated with phosphorylation
      of a protein of approximately 100 kDa and proteins of the MAPK family. The former
      was selectively phosphorylated by alpha-adrenergic stimulation whereas the latter
      were phosphorylated by the binding of cells to Fg and markedly intensified by
      alpha-adrenergic stimulation.

PMID- 15583747
TI  - A variant thrombasthenic phenotype associated with compound heterozygosity of
      integrin beta3-subunit: (Met124Val)beta3 alters the subunit dimerization
      rendering a decreased number of constitutive active alphaIIbbeta3 receptors.
AB  - We report the analysis of a variant case of thrombasthenic phenotype that is a
      compound heterozygote for two mutations located within the metal ion dependent
      adhesion site (MIDAS) of the beta3 subunit. The patient inherited a maternal
      allele carrying the Met124Val substitution and a paternal allele that changes
      Asp119 to Tyr. Phenotyping of the human platelet antigen 1 (HPA-1) showed that
      the platelet alphaIIbbeta3 complex in the patient was mostly accounted for by the
      Asp 119Tyr allele that does not bind to fibrinogen (Fg). The patient showed
      agonistinduced binding of platelets to Fg but neither binding to PAC-1 nor cell
      aggregation could be detected, most likely due to the minute expression (< or =
      5%) of alphaIIb(124Val)beta3 receptors. CHO cells expressing (124Val)beta3 showed
      a diminished surface expression of alphaIIbbeta3, enhanced adhesion to
      immobilized Fg, and spontaneous aggregation in the presence of soluble Fg,
      suggesting that (124Val)beta3 may confer constitutive activity to the
      alphaIIb(124Val)beta3 receptors. A distinct feature of these cells is the failure
      of DTT to enhance the binding to soluble Fg and the formation of cell aggregates.
      The substitution of (124Met)beta3 by either a polar or a positively charged amino
      acid restored the surface exposure and function of the alphaIIbbeta3 receptors
      whereas a negatively charged residue did not.

PMID- 15583748
TI  - Effect of selective inhibition of the p38 MAP kinase pathway on platelet
      aggregation.
AB  - Systemic inflammation has been shown to be a contributing factor to the
      instability of atherosclerotic plaques in patients with acute coronary syndromes
      (ACS). VX-702, a novel p38 mitogen-activated protein kinase (MAPK) inhibitor, is
      currently under investigation in ACS patients with unstable angina to evaluate
      its safety and efficacy during percutaneous coronary intervention (PCI). The role
      of p38 MAPK in platelet aggregation of normal individuals was examined using the
      selective second generation p38 MAPK inhibitor VX-702. Treatment of platelets
      with thrombin (activates PAR1 and PAR4 thrombin receptors), SFLLRN (PAR1), AYPGKF
      (PAR4), collagen (alpha2beta1 and GPVI/FCgammaIIR receptors) and U46619 (TXA(2))
      resulted in strong activation of p38 MAPK. Activation of the GPIb von Willebrand
      factor receptor with ristocetin did not stimulate p38 MAPK. Pre-treatment of
      platelets with 1 microM VX-702 completely inhibited activation of p38 MAPK by
      thrombin, SFLLRN, AYPGKF, U46619, and collagen. There was no effect of VX-702 on
      platelet aggregation induced by any of the agonists in the presence or absence of
      aspirin, heparin or apyrase. It has been postulated that a potential role of p38
      MAPK is to activate phospholipase A(2) (cPLA(2)) which catalyses formation of
      arachidonic acid leading to production of thromboxane. Interestingly, we show
      contrasting effects of p38 MAPK inhibition as compared to aspirin inhibition on
      platelet aggregation in response to collagen. Blockade of TXA(2) production by
      aspirin results in significant inhibition of collagen activation. However,VX-702
      has no effect on collagen-mediated platelet aggregation, suggesting that blocking
      p38 MAPK does not effect thromboxane production in human platelets. Therefore,
      unlike aspirin blockade of thromboxane production in platelets, p38 MAPK
      inhibitors such as VX-702 do not significantly affect platelet function and would
      not be expected to contribute to an elevated risk of bleeding side-effects in
      treated patients.

PMID- 15583749
TI  - Platelet deposition on stainless steel, spiral, and braided polylactide stents. A
      comparative study.
AB  - Platelets play a key role in (sub)acute thrombotic occlusion after stenting. We
      examined the possible differences between biodegradable polylactide (PLA) and
      stainless steel (SS) stents in platelet attachment and morphology after whole
      blood perfusion. PLA stents of different configurations (spiral/braided) and
      polycaprolactone-polylactide (PCL-PLA)-coatings, or SS stents were implanted into
      a PVC tube (O 3.2 mm), with or without precoating of the tube with type-I
      collagen. PPACK (30 microM)-anticoagulated blood with (3)H-serotonin prelabeled
      platelets was perfused (flow rate: 30 ml/min, 90 s) over the stents. Platelet
      deposition was assessed by scintillation counting and morphology by scanning
      electron microscopy (SEM). To examine coagulation activation, plasma prothrombin
      fragments (F1 + 2) were measured before and after the perfusion. Protein
      deposition on PLA/SS stents was assessed at augmented shear forces mimicking
      coronary flow (rate: 60 ml/min, 60 s) under minimal anticoagulation (PPACK 1
      microM). More platelets deposited on PLA stents than on SS stents under all study
      conditions (p < 0.03). Under anticoagulation (PPACK 30 microM) the generation of
      F1 + 2 remained unaltered. Under higher flow rate and limited anticoagulation SS
      stents accumulated 3.27 +/- 0.75 microg and PLA stents 5.25 +/- 1.74 microg of
      protein (Mean +/- SD, p <0.95). Among all biodegradable stents, the braided PLA
      stent coated with PCL-PLA-heparin accumulated the fewest platelets (p < 0.02). In
      SEM, signs of platelet activation on braided heparin-coated PLA stents, when
      compared with uncoated braided PLA/SS stents, appeared modest. In conclusion, PCL
      PLAheparin coating of biodegradable stents may enhance their hemocompatibility,
      expressed by less platelet deposition. Nevertheless, materials, design, and
      coating techniques of biodegradable stents must be further developed.

PMID- 15583750
TI  - Inhibition of monocyte, lymphocyte, and neutrophil adhesion to endothelial cells
      by human milk oligosaccharides.
AB  - Excessive leukocyte infiltration causes severe tissue damage in a variety of
      inflammatory diseases. The initial step in leukocyte extravasation is mediated by
      selectins and oligosaccharides on their glycoconjugate ligands. Human milk is a
      rich source of lactose-derived oligosaccharides that are partly absorbed in the
      intestine and excreted with the urine. As these components contain binding
      determinants for the selectins we investigated whether human milk
      oligosaccharides are able to affect leukocyte rolling and adhesion to endothelial
      cells under dynamic conditions. Therefore, monocytes, lymphocytes, or neutrophils
      isolated from human peripheral blood were passed over TNF-alpha-activated HUVEC
      under shear stress. The influence of different oligosaccharide fractions was
      determined by video-microscopy and compared with the effects of various
      individual oligosaccharides. Within a physiological range (12.5 - 125 microg/ml)
      the acidic fraction significantly inhibited leukocyte rolling and adhesion (up to
      24.0% and 52.8%, respectively) in a concentration-dependent manner. These effects
      were even more pronounced than those achieved by soluble sialyl-Lewis x, a
      physiological binding determinant for selectins. Several active components within
      the oligosaccharide fraction of human milk were identified, e.g. 3'-sialyl
      lactose and 3'-sialyl-3-fucosyl-lactose. These results indicate that specific
      oligosaccharides in human milk may serve as anti-inflammatory components and
      might therefore contribute to the lower incidence of inflammatory diseases in
      human milk-fed infants.

PMID- 15583751
TI  - Polymorphonuclear leukocyte and monocyte activation induced by plasma from
      patients with heparin-induced thrombocytopenia in whole blood.
AB  - Heparin-induced thrombocytopenia (HIT), a severe complication of heparin therapy,
      results from platelet activation by heparin-dependent antibodies. Previously, we
      have shown that plasma from patients with HIT (HIT plasma) induces
      leukocyteplatelet aggregation in blood. In this report, we examined leukocyte
      activation by HIT plasma and the contribution of heparin and platelets to this
      activation, in whole blood. Degranulation of leukocytes from HIT patients was
      evaluated as a leukocyte activation marker. We showed that polymorphonuclear
      leukocytes (PMN) and monocytes were the leukocyte subpopulations involved in
      platelet-leukocyte aggregation induced by HIT plasma in healthy donor blood. PMN
      and monocyte activation, reflected by increased surface expression of the CD11b
      adhesion molecule, was induced by HIT plasma in a heparin-dependent manner. The
      CD11b increase induced by HIT plasma was observed on PMN only when they were
      associated with platelets. Moreover, the increased CD11b expression on monocytes
      and PMN correlated strongly with the degree of platelet adhesion to these cells.
      Degranulation of leukocytes from HIT patients and control subjects (non-HIT
      heparin-treated patients and healthy subjects) was evaluated in vivo by measuring
      the plasma myeloperoxidase concentration. HIT plasma contained higher
      myeloperoxidase concentrations than control plasma, suggesting leukocyte
      degranulation during HIT. In conclusion, this study provides the first evidence
      that PMN activation is induced by HIT plasma. HIT plasma induced PMN and monocyte
      activation in a heparin-dependent manner. In whole blood, platelet association
      with monocytes and PMN, and the activation of these leukocytes by HIT plasma were
      interrelated. Finally, leukocyte degranulation could be involved in HIT
      physiopathology.

PMID- 15583752
TI  - Inhibition of the endothelial cell activation by antithrombin in vitro.
AB  - We examined whether antithrombin (AT) inhibits tumor necrosis factor (TNF)-alpha
      induced endothelial cell activation to elucidate molecular mechanism(s) of the
      anti-inflammatory activity of AT. AT inhibited the increase in E-selectin
      expression in cultured human umbilical vein endothelial cells (HUVECs) stimulated
      with TNF-alpha. In contrast, chemically modified AT that lacks affinity for
      heparin did not. AT inhibited the TNF-alpha-induced interaction of NF-kappaB p65
      with p300, a homologue of cAMP-responsive element binding protein (CREB)-binding
      protein (CBP). AT increased both intracellular levels of cAMP and binding of
      phosphorylated-CREB to DNA in HUVECs. Forskolin showed the inhibitory effect
      similar to that of AT and pretreatment of HUVECs with KT-5720, an inhibitor of
      protein kinase A, reversed the inhibitory effect of AT. These observations
      suggested that AT inhibited the TNF-alpha-induced increase in E-selectin
      expression in HUVECs by inhibiting the interaction of NF-kappaB with CBP/p300
      through cAMP-dependent protein kinase A-induced CREB activation. This inhibitory
      activity of AT might depend on its binding to heparin-like substances on the
      endothelial cell. Such an inhibitory effect of AT on TNF-alpha-induced
      endothelial cell activation might at least partly contribute to its anti
      inflammatory activity.

PMID- 15583753
TI  - Proinflammatory properties of murine aortic endothelial cells exclusively
      expressing a non cleavable form of TNFalpha. Effect on tumor necrosis factor
      alpha receptor type 2.
AB  - Soluble (sTNF) and transmembrane (tmTNF) forms of TNFalpha (TNF) have distinct
      proinflammatory effects. We investigated whether tmTNF altered the synthesis of
      some proinflammatory proteins involved in atherothrombosis, in murine aortas and
      aortic endothelial cells (MAEC). Samples were obtained from wild-type (WT) mice
      and TNF-deficient mice that express a mutated non cleavable tmTNF transgene
      (tmTNFnc). The levels of secreted MCP-1, RANTES, IL-6, PAI-1, soluble ICAM-1, and
      soluble TNF receptor type 1 (TNFR1; CD120a) antigens, MMP-9 activity and of cell
      surface ICAM-1 were not significantly different between the two types of MAEC.
      The magnitude of endotoxin-stimulated production of RANTES, MCP-1 and IL-6 was
      similar in the two types of cells. Of note, the amount of synthesized TNF
      receptor type 2 (TNFR2; CD120b), measured by its secreted (in aorta and MAEC),
      intracellular and mRNA levels (in MAEC), was significantly 4-fold lower in
      tmTNFnc than in WT mice, both in basal and endotoxin-stimulated conditions. A
      neutralizing anti-TNF antibody or the recombinant murine TNF did not modify the
      magnitude of the difference in TNFR2 production between the two types of cells,
      suggesting a preponderant role of tmTNF in the down-regulation of TNFR2
      synthesis. Macrophages of tmTNFnc mice also produced less TNFR2 than WT
      macrophages (-30%). Plasmas of tmTNFnc mice contained significantly less sTNFR2
      than WT mice (-75%). In conclusion, an increase in tmTNF levels, rather than the
      lack of sTNF, significantly down-modulated TNFR2 synthesis in aortic endothelial
      cells, but had no major influence on the synthesis of some major pro-inflammatory
      and pro-atherothrombotic proteins.

PMID- 15583754
TI  - A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in
      bone marrow endothelial cells of patients with multiple myeloma.
AB  - The expression/function of vascular endothelial growth factor (VEGF) and its
      receptor 2 (VEGFR-2/KDR) in multiple myeloma (MM)-associated angiogenesis is
      under scrutiny. We show here that bone marrow endothelial cells (EC) from 16
      patients with MM (MMEC) highly expressed VEGF-A (the main VEGF isoform) and VEGFR
      2 at both mRNA and protein level, whereas EC from 14 patients with monoclonal
      gammopathy unassociated/unattributable (MG[u]) (MG[u]EC) and 12 human umbilical
      veins (HUVEC) expressed very low mRNAs and/or proteins. MMEC showed constitutive
      autophosphorylation in both VEGFR-2 and the associated extracellular signal
      regulated kinase-2 (ERK-2), whereas this was marginal in MG[u]EC and HUVEC. MMEC
      proliferated rapidly and formed a closely-knit capillary meshwork on Matrigel.
      These cell functions were reduced in the other EC. Autophosphorylation,
      proliferation and capillarogenesis were prevented by a neutralizing anti-VEGF-A
      antibody, and more efficaciously by an anti-VEGFR-2 antibody. Both antibodies had
      no effect or were poorly effective on the other EC. These findings as a whole
      suggest the existence of an autocrine loop of VEGF in MMEC. Since this is very
      likely a mechanism for the amplification of VEGF activity in neovascularization,
      it would constitute an appropriate target for antiangiogenic management in MM.

PMID- 15583755
TI  - Recombinant factor VIIa in a patient with Glanzmann's thrombasthenia undergoing
      gynecological surgery: open issues in light of successful treatment.

PMID- 15583756
TI  - Correlation between platelet-derived microparticles and soluble L-selectin in
      patients undergoing hemodialysis.

PMID- 15583757
TI  - Rebuttal: accidental overdosage of recombinant factor VIIa due to mistaken
      package size: an inappropriate case report.

PMID- 15583758
TI  - Are only haemophiliacs protected against ischemic heart disease?

PMID- 15583760
TI  - [Breastfeeding: a scientific contribution to the practice of health care
      providers].

PMID- 15583761
TI  - [Breastfeeding: a nature-culture hybrid].
AB  - OBJECTIVE: To contribute to the creation of a new theoretical synthesis about the
      relationship between the biological and social dimensions of breastfeeding,
      categorizing it as a nature-nurture hybrid. SOURCES OF DATA: The methodological
      approach of the present article was based on the qualitative health research
      frame, and data were analyzed on the basis of dialectic-hermeneutic principles.
      Primary sources, comprising historical documents, books, scientific articles and
      medical theses written in the 19th and 20th centuries were analyzed. SUMMARY OF
      THE FINDINGS: Depending on the moment in history and on the expectations that
      surround the act of breastfeeding, the aspects related to nature and nurture,
      i.e., to biology and society, sometimes separate out and sometimes intermingle. A
      comprehensive approach to breastfeeding makes possible to see that it had to be
      considered instinctive, natural and biological in order to be assimilated as a
      cultural habit, and thus, it is not open to any kind of questioning. On other
      occasions, particularly in the course of the past decade, there has been a steady
      tendency to supplant traditional biological reductionism, which yielded cultural
      interpretations that do not reduce the human being to the status of a mammal like
      any other. Under this point of view, breastfeeding, in addition to being
      biologically determined, is socially conditioned, and thus constitutes an act
      embedded in ideologies and determinants resulting from the concrete conditions of
      life. In real life, however, a process apparently so natural, so loaded with
      affection and emotion is, in fact, affected by the most aggressive market
      interests, very often presented as scientific knowledge and decked out as health
      provisions. CONCLUSION: Breastfeeding focused as a nature-culture hybrid
      symbolizes the theoretical and methodological changes in the field, especially in
      the late 1990s. These changes reflect a renewed appreciation of biology and a
      more in-depth approach to interdisciplinary processes.

PMID- 15583762
TI  - [The practice of breastfeeding counseling].
AB  - OBJECTIVE: To provide health professionals with information on theory and
      practice of breastfeeding counseling. SOURCES OF DATA: MEDLINE, Bireme library,
      Lilacs, relevant Internet websites, scientific journals, technical books, essays,
      theses, and national and international publications were selected, studied and
      used to provide information on the topic. The most important sources of data
      were: a publication by the World Health Organization (WHO - 1993) and the
      authors' experience and clinic practice in the assistance of mothers, children
      and families. SUMMARY OF THE FINDINGS: A trained pediatrician plays a relevant
      role on increasing breastfeeding rates and its duration. To improve this
      performance, in 1993, WHO designed a 40-hour course using an important didactic
      strategy aimed at health professionals and mothers. The goal was to protect,
      promote and support maternal nursing. It is a professional way of dealing with
      the mother by listening and trying to understand her, offering her help on
      planning, taking decisions, and getting strength on how to deal with pressures,
      thus increasing her confidence and self-esteem. CONCLUSION: Scientific evidence
      proves the effectiveness of Breastfeeding Counseling. Moreover, health
      professional's knowledge and practice are very important to increase
      breastfeeding rates.

PMID- 15583763
TI  - [Recommendations for the complementary feeding of the breastfed child].
AB  - OBJECTIVE: To present a review on the evidence that support the current
      recommendations for breastfed children feeding. SOURCES OF DATA: An extensive
      bibliographic review of the topic was carried out. Articles selected in the
      MEDLINE and Lilacs databases, publications from national and international
      organizations, theses and dissertations were reviewed. Some key articles were
      also selected from the citations referred in other papers. SUMMARY OF THE
      FINDINGS: New knowledge acquired about child feeding over the last 20 years have
      led to a significant change in the current feeding recommendations for breastfed
      children in relation to the prior recommendations. The current recommended
      nutritional needs are lower than the old recommendations, complementary food is
      introduced in a more precise age, around 6 months, and new methods are
      recommended for promoting the child's healthy eating. The new recommendations
      emphasize the health feeding practices which comprise both the adequate food
      quantity and quality, including care with food handling and preparation, feeding
      and storage practices, and the respect and adequacy to the cultural
      characteristics of each people. CONCLUSIONS: The adequate complementary feeding
      of the breastfed child is critical for the optimal child growth and development.
      Therefore, it is an essential factor for both the populations food security and
      the development of nations. The health professionals ought to effectively pass on
      to mothers/care takers the new recommendations for promoting the healthy
      complementary feeding of the breastfed child. It is up to the governments to
      provide the adequate conditions for supporting such a promotion.

PMID- 15583764
TI  - [Benefits of breastfeeding and women's health].
AB  - OBJECTIVE: To review breastfeeding benefits for the women's health. SOURCES OF
      DATA: Lilacs, MEDLINE, SciELO, BIREME, Cochrane Library and Google were searched
      for the keywords: breastfeeding and breast cancer, ovarian cancer, osteoporosis,
      rheumatoid arthritis, lactation amenorrhea, post natal period, and women's
      health. Single articles published between 1990 and 2004 were considered, as well
      as remarkable ones prior to this period. SUMMARY OF THE FINDINGS: There are a few
      articles published on the topic, even though, the existing literature reveals
      that there is a positive relationship between breastfeeding and decreased risk of
      breast cancer, cancer of the ovarian epithelium, and osteoporosis leading to hip
      fracture. Some studies suggest the effect of breastfeeding on the decreasing risk
      of rheumatoid arthritis, others mention the relation between breastfeeding and
      faster loss of weight gained during the gestational period. Several studies show
      how breastfeeding interferes on the onset of postnatal menstruation and
      consequent birth spacing. CONCLUSIONS: Breastfeeding provides important benefits
      for the women's health, such as reduced risk of breast and ovarian cancer,
      decreased risks of hip fractures and contribution to the increase of birth
      spacing.

PMID- 15583765
TI  - [Common problems during lactation and their management].
AB  - OBJECTIVE: To present an updated review on common problems associated with
      breastfeeding and their management. SOURCE OF DATA: A comprehensive bibliographic
      review on the issue was performed by searching publications from the MEDLINE
      database and from national and international organizations. Books and some key
      articles cited in other sources were also selected. SUMMARY OF THE FINDINGS:
      Several common problems that may arise during the breastfeeding period, such as
      breast engorgement, plugged milk duct, breast infection and insufficient milk
      supply, originate from conditions that lead the mother to inadequate empty the
      breasts. Incorrect techniques, not frequent breastfeeding and breastfeeding on
      scheduled times, pacifiers and food suppliers are important risk factors that can
      predispose to lactation problems. The adequate management of those conditions is
      fundamental, as if not treated they frequently lead to early weaning. There are
      specific measures that should be taken to empty the breasts effectively. Besides,
      the emotional support and actions that yield more comfort to the lactating mother
      can not be neglected. CONCLUSIONS: Most common problems associated with
      breastfeeding can be prevented if the mother empties her breasts effectively. If
      they occur, they should be carefully and adequately approached, thus avoiding the
      early weaning resultant from painful and stressing situations the mother may
      face.

PMID- 15583766
TI  - [Clinical management of oral disorders in breastfeeding].
AB  - OBJECTIVE: To address aspects associated with the early detection and clinical
      management of oral disorders in breastfeeding. SOURCE OF DATA: Review of
      bibliographic sources (research articles, technical books, dissertations and
      national and international publications) focused on the clinical management of
      oral disorders in breastfed babies. SUMMARY OF THE FINDINGS: Suction disorders
      may lead to inadequate actions that can compromise the mother/baby relation
      during breastfeeding. Healthcare professionals may have an important role in
      these cases, as they can detect such disorders early. For that end, they must be
      able to assess breastfeeding and be prepared to manage oral disorders clinically.
      In the clinical management of babies with breastfeeding difficulties significant
      aspects of the oral physiology and breastfeeding observation should be
      considered. We stress the importance of an interdisciplinary team work and the
      need for oral training and specialized care in most complex cases. CONCLUSION:
      The baby's oral disorders in breastfeeding can be corrected if they were early
      detected. Healthcare professionals may help mothers and babies to overcome these
      problems if they have knowledge that enable them to perform right clinical
      procedures.

PMID- 15583767
TI  - [Breastfeeding in premature infants: in-hospital clinical management].
AB  - OBJECTIVE: To describe the importance of breastfeeding and its promotion in the
      in-hospital clinical management of premature newborns. SOURCE OF DATA: The
      authors made an extensive literature review on the topic, including technical
      books, theses, publications of national and international organizations, and
      search on MEDLINE database (1990 to 2003), using the following key words and
      boolean operators: "breastfeeding AND low birth weight" and "breastfeeding AND
      preterm infant". Some significant references cited in the reviewed publications
      were used as well. SUMMARY OF THE FINDINGS: After this review we conclude that
      many aspects make the breast milk particularly suitable to the premature newborn
      feeding. Despite being highly desirable, little success in breastfeeding preterm
      infants is generally observed, particularly in special care neonatal units,
      although there is evidence suggesting that a highly supportive hospital
      environment can make it possible to breastfeed these infants. CONCLUSIONS:
      Although breastfeeding premature infants represents a challenge, it is feasible
      if appropriate help and support are provided. Mothers of premature infants need
      information and support to make informed decisions about their infant's feeding.

PMID- 15583768
TI  - [Kangaroo-Mother Care: scientific evidence and impact on breastfeeding].
AB  - OBJECTIVE: To describe the history of the Kangaroo Mother Care and present
      scientific evidence about benefits of this practice on morbidity and mortality,
      psychological and neurological development and breastfeeding of low birth weight
      infants. SOURCES OF DATA: Papers about Kangaroo Mother Care published from 1983
      to 2004 were consulted, selected in Medline and Lilacs, as well as books, thesis
      and technical publications from the Brazilian Health Department. SUMMARY OF THE
      FINDINGS: Since its first description, Kangaroo Mother Care has been extensively
      studied. The analysis of randomized trials showed that it consists in a
      protection factor to breastfeeding at discharge (relative risk 0.41, 95%
      confidence interval 0.25 to 0.68). The method was always associated with the
      following reduced risks: nosocomial infection at 41 weeks' corrected gestational
      age (relative risk 0.49, 95% confidence interval 0.25 to 0.93), severe illness
      (relative risk 0.30, 95% confidence interval 0.14 to 0.67), lower respiratory
      tract disease at 6 months (relative risk 0.37, 95% confidence interval 0.15 to
      0.89) and better gain of weight per day (weighted mean difference 3.6 g/day, 95%
      confidence interval 0.8 to 6.4). Psychomotor development at 12 months' corrected
      age was similar in the two groups. There was no evidence of a difference in
      infant's mortality. CONCLUSIONS: A positive impact of Kangaroo Mother Care on
      breastfeeding was found. Although the method appears to reduce severe infant
      morbidity without any serious deleterious effect reported, there is still
      insufficient evidence to recommend its routine use. It is necessary to develop
      studies about effectiveness, acceptability and applicability of the method in the
      Brazilian context.

PMID- 15583769
TI  - [Recommendations for breastfeeding during maternal infections].
AB  - OBJECTIVE: To make a literature review on breastfeeding and maternal infectious
      diseases in order to contribute with knowledge and information that can aid the
      pediatrician to decide upon allowing infected mothers to breastfeed their babies
      or not. SOURCES OF DATA: Lilacs and MEDLINE databases were searched for books,
      technical rules and articles on the issue of breastfeeding and infected mothers.
      SUMMARY OF THE FINDINGS: Infected lactating mothers can transmit pathogenic
      agents to their infants. Although breastfeeding protects the child it can also be
      a dangerous source of infection. Maternal diseases caused by bacteria, virus,
      fungi and parasites may sometimes be transmitted via human milk. The literature
      points out that mothers infected with HIV and T-lymphotropic human viruses (type
      I) should not breastfeed. With other diseases a careful approach should be taken,
      but in general breastfeeding is maintained. CONCLUSION: The mother who is exposed
      to infectious diseases may transmit pathogenic agents through the human milk,
      attention should also be made to milk from milk banks. The healthcare provider
      must take his/her decision upon suspending breastfeeding -- or not, what can be
      distressful, once he/she has a fundamental role in promoting and stimulating
      breastfeeding.

PMID- 15583770
TI  - [Breastfeeding and maternal medications].
AB  - OBJECTIVE: To contribute with information about the adequate administration of
      drugs during breastfeeding. SOURCES OF DATA: MEDLINE articles from 1993 to 2004,
      and Lilacs articles from 1995 to 2004 were selected in Portuguese, Spanish and
      English, by including the following keywords: breastfeeding, lactation, drugs and
      medicines. Other updated references found in articles and books were also
      included in this review, in order to provide additional information. SUMMARY OF
      THE FINDINGS: Most of the drugs are compatible with breastfeeding. Few were
      considered inadequate, such as antineoplastic drugs, radiopharmaceuticals and
      drugs of abuse. Some drugs require concern, as they may cause adverse effects in
      breastfed babies or reduce the mother's breast milk volume. However, further
      knowledge on some medicines during lactation is required. CONCLUSION: The
      fundamental principle in the prescription of medicines for lactating mothers is
      mostly based on the concept of risk and benefit. The option must be, as much as
      possible, for a drug that has already been studied, which is little released in
      the maternal milk or that does not mean an apparent risk for the infant's health.
      Medicines that reduce the mother's production of milk should be avoided during
      the lactation period. The use of galactogogos is reserved for particular
      situations. Therefore, only safety drugs should be administered during
      breastfeeding, which should rarely be discouraged or discontinued in such cases.

PMID- 15583771
TI  - [Breastfeeding and early childhood caries: a critical review].
AB  - OBJECTIVE: To find scientific evidence that can prove or refute the assumption
      that nocturnal and on demand breastfeeding are associated with caries in infants
      and preschool children. SOURCES OF DATA: MEDLINE, Lilacs, and SciELO articles
      were searched, as well as important internet sites, technical books and consensus
      publications of national and international organisms. The following keywords were
      used: "early childhood caries", "dental caries", "dental decay" and
      "breastfeeding". References cited in the articles selected were also included.
      SUMMARY OF THE FINDINGS: Studies associating caries with breastfeeding invariably
      observe factors associated with how this disease develops, letting aside those
      associated with breastfeeding. Many of these factors act as confusing variables
      because in the same way as they interfere in breastfeeding, they also influence
      the development of caries. Besides, current studies have already demonstrated the
      cariogenic potential of some types of aliments given to children against the non
      cariogenic potential of the human milk. CONCLUSIONS: There is no scientific
      evidence proving that human milk can be associated with the development of
      caries. This is a complex relation to be established, as it is often blurred by
      too many variables.

PMID- 15583772
TI  - The Special Olympics athlete: evaluation and clearance for participation.
AB  - Evaluating and clearing the Special Olympics athlete for participation in sports
      and recreational activities can be a challenging task for a primary care
      physician. Radiographic clearance of the cervical spine is mandatory for all
      athletes with Down syndrome. Regular physical activity for this special
      population has measurable physiologic and psychosocial benefits.

PMID- 15583773
TI  - ENT and speech disorders in children with Down's syndrome: an overview of
      pathophysiology, clinical features, treatments, and current management.
AB  - Down's syndrome is the most commonly occurring genetic abnormality, involving
      about 1 in 600 births. The increasing life expectancy of individuals with Down's
      syndrome has revealed the presence of several unexpected pathological processes.
      Among these, ENT disorders hold an important place because of their high
      incidence and severity. Accurate knowledge of the pathophysiology underlying ENT
      disorders (facial dysmorphism, ear abnormalities, upper airway abnormalities, and
      immunodeficiency) allow an understanding of the reasons for the development of
      the upper airway obstruction, obstructive sleep apnea syndrome, subglottic
      stenosis, deafness, speech delay, and ENT infections that occur frequently in
      these children. Early screening and specific treatment may allow some of the long
      term sequelae to be avoided, or at least their prognosis to be improved. In order
      to help health care professionals in their daily practice, this review makes a
      series of recommendations to allow them to develop a master plan for the ENT
      management of children with Down's syndrome. In children with Down's syndrome,
      ENT disorders occur frequently and are often severe. They develop owing to
      craniofacial, functional, and immune system abnormalities. Early screening and
      treatment allow improvements in long-term outcomes.

PMID- 15583774
TI  - Update on National Asthma Education and Prevention Program pediatric asthma
      treatment recommendations.
AB  - The National Asthma Education and Prevention Program (NAEPP) published an update
      on selected topics from the 1997 Guidelines for the Diagnosis and Management of
      Asthma and provided new evidence-based recommendations for asthma treatment.
      Selected topics on the long-term management of asthma in children addressed the
      efficacy of inhaled corticosteroids (ICSs) compared with other asthma medications
      (i.e., as-needed beta(2)-adrenergic agonists and other controllers) in mild and
      moderate persistent asthma and the safety of long-term ICS use. The effects of
      early intervention with ICSs on asthma progression also were evaluated. An
      important new aspect of the treatment update entails the recommendation of ICSs
      as the controller medication of choice for all severities of persistent asthma in
      children. Additionally, on the basis of studies in adults, the Expert Panel
      suggested that long-acting beta(2)-adrenergic agonists are now the preferred
      adjunct to ICSs in children with moderate or severe persistent asthma. Based on
      long-term data in children, ICS therapy was deemed safe in terms of growth, bone
      mineral density, ocular effects, and hypothalamic pituitary adrenal axis
      function. Although members of the NAEPP Expert Panel determined that the effects
      of early intervention with ICSs on decline in lung function have not been
      adequately studied, they found that the effects on asthma control were
      substantial.

PMID- 15583775
TI  - Child deaths of unknown cause: review of 7 years' experience.
AB  - Using data from the Pima County (Arizona) Child Fatality Review Team, we sought
      to describe the nature of unknown cause pediatric deaths. Of 1,150 total deaths
      (1995-2001), 22 were unknown cause and 3 had only a mode of death on the death
      certificate. There were 15 infants <6 months, 4 children 1-4 years, 2 children 5
      9 years, 1 preteen (10-14 years), and 3 aged 15-17 years. Four patterns were
      seen: those resembling SIDS but with confounding history, autopsy, or scene
      investigation; sleeping toddlers with respiratory symptoms; children with
      underlying conditions not expected to cause death; and deaths without complete
      investigation.

PMID- 15583776
TI  - A prospective study of the "two-bag system'' in diabetic ketoacidosis management.
AB  - The "two-bag'' system, an adaptation of the euglycemic clamp technique, consists
      of simultaneous administration of 2 intravenous (IV) fluid bags of differing
      dextrose concentrations. Individualized therapy is dictated by adjustment of the
      infusion rate of each bag. We sought to assess the benefits of the two-bag system
      in the initial acute emergency department management of children in diabetic
      ketoacidosis (DKA). Thirty-three children presenting to an urban pediatric
      emergency department in DKA were randomized into 2 groups: patients managed with
      the two-bag system and patients managed with the traditional "one-bag'' system.
      Other aspects of the management were standardized. Outcome measures included rate
      of decline in serum glucose, rate of bicarbonate correction, time on IV insulin
      therapy, and response time for IV fluid changes. Study period was defined as time
      on IV insulin therapy. There were no differences between the 2 groups in
      demographic parameters, initial baseline metabolic parameters, or total time on
      IV insulin therapy. There were no differences between the groups in average rates
      of serum glucose decline: two-bag 33.1 mg/dL/hr (s.e. 5.57, 95% CI 22.2, 44), one
      bag 30.2 mg/dL/hr (s.e. 5.72, 95% CI 19, 41.4); average rate of serum bicarbonate
      correction: two-bag 1.19 mEq/L/hr, one-bag 1.27 mEq/L/hr; or the average number
      of IV fluid bags used: two-bag 4.1 bags, one-bag 3.2 bags. However, there was a
      difference between the groups in regard to elapsed total time to make changes in
      the IV fluids: two-bag 1 minute, one-bag 42 minutes, (p < 0.001). The "two-bag''
      system enables a faster response time in making IV fluid therapy changes. This
      efficiency makes this system ideal for use in the emergency department.

PMID- 15583777
TI  - Regional and sociodemographic variation of breastfeeding in the United States,
      2002.
AB  - With use of data from the Ross Mothers Survey (RMS), rates for breastfeeding in
      the hospital and at 6 months of age were evaluated within 4 geographical regions
      of the United States. Odds ratios for determinants of breastfeeding were also
      calculated. Regardless of sociodemographic characteristics, breastfeeding in the
      hospital and at 6 months of age was most common in the West and least common in
      the South. College education and not participating in the Women, Infants, and
      Children (WIC) program were the strongest predictors of breastfeeding in the
      hospital. Not working outside the home and not participating in WIC were the
      strongest predictors of continued breastfeeding to 6 months of age. Region of
      residence is important in considering how to develop programs targeted to
      populations with lower breastfeeding rates.

PMID- 15583778
TI  - Risk factors for development of nontyphoid Salmonella bacteremia.
AB  - The objective of this paper was to identify risk factors for nontyphoid
      Salmonella bacteremia by making a retrospective chart review of 39 patients with
      nontyphoid Salmonella bacteremia. The control group included 30 patients with
      positive Salmonella stool culture (gastroenteritis group). Demographic factors,
      presenting signs and symptoms, antimicrobial treatment before admission, and
      microbiologic results were recorded. Nine patients (23%) were excluded owing to
      recognized risk factors for development of extraintestinal disease. Seventeen
      cases (57%) occurred during summer time, whereas the gastroenteritis group had a
      less seasonal tendency. Eighty percent of the patients with Salmonella bacteremia
      had a previous history of diarrhea. At admission more patients in the bacteremia
      group were febrile and had leukocytosis (73% vs 33% and 37% vs 20%,
      respectively). More patients in the bacteremia group had previous antibiotic
      treatment (57% vs 20%, p<0.01). The Salmonella types were mainly C and D in the
      bacteremia group (40% each), and B and C in the gastroenteritis group (26% and
      52%, respectively). The risk factors for Salmonella bacteremia in previously
      healthy children include warm season, previous gastrointestinal illness, and
      preexposure to antibiotics.

PMID- 15583779
TI  - Subnormal immunity to Hemophilus influenzae type b (Hib) in previously vaccinated
      human immunodeficiency virus-infected children 59 months of age or older and
      response to booster doses of the conjugate vaccine.

PMID- 15583780
TI  - Propionic acidemia revisited: a workshop report.
AB  - Propionic acidemia (PA) is one of the most frequent organic acidurias, but
      information on the outcome of individuals with PA is rather limited. We present
      data of 49 patients with PA, which were gathered from 18 metabolic centers
      throughout Central Europe on the occasion of an international workshop. All
      patients were identified by selective metabolic screening, and 86% of them were
      classified as having early-onset PA owing to their presentation with clinical
      symptoms within the first 90 days of life. Mortality rate was one third, and
      details of symptoms and treatment of the surviving patients are discussed. The
      great variation of phenotypic expression of the disease and different therapeutic
      strategies (especially in regard to the degree of protein restriction) used at
      the various institutions involved in this study imply the need for a registry of
      PA patients and for a multicenter prospective treatment study.

PMID- 15583781
TI  - Family lead poisoning associated with occupational exposure.

PMID- 15583782
TI  - Treatment of inferior vena cava and renal vein thrombosis with low-molecular
      weight heparin in a child with idiopathic membranous nephropathy.

PMID- 15583783
TI  - Permanent brain damage from hypernatremic dehydration in breastfed infants:
      patient reports.

PMID- 15583784
TI  - Hip pain.

PMID- 15583786
TI  - Pediatric chest pain.

PMID- 15583787
TI  - The combination of bilateral congenital adrenal hemorrhage and congenital
      hemihypertrophy.

PMID- 15583789
TI  - Transfusion of blood products affects outcome in cardiac surgery.
AB  - There remains controversy as to when patients undergoing cardiac surgery should
      receive a transfusion and whether a low hematocrit and its treatment with a
      transfusion of red cells influences outcome. The data related to this controversy
      are reviewed. Although the risk of known viral transmission is currently low,
      stored red cells do not function normally, and each unit contains activated
      inflammatory cells and mediators. These changes cause limited oxygen release,
      impaired microcirculatory flow, and immune suppression. A number of studies have
      observed decreased survival associated with transfusions in trauma, coronary
      artery bypass grafting, and intensive care unit patients. Studies that show an
      adverse outcome associated with low hematocrit are not definitive, because they
      fail to distinguish between the impact of low hematocrit per se and the possible
      adverse effects of transfusion, for what the low hematocrit may simply be a
      surrogate. The observation that a low hematocrit is associated with an adverse
      outcome does not necessarily prove that "treatment" of the anemia with a red cell
      transfusion will improve the outcome. Stored platelets contain a highly activated
      mixture of platelets with storage lesions and inflammatory mediators. Two
      retrospective post hoc multifactorial analyses suggest that platelet transfusions
      are associated with substantial increased morbidity and mortality. Clearly, large
      prospective studies are required to define the proper trigger for blood product
      transfusion to balance the adverse effects of anemia and platelet deficiency or
      dysfunction with the adverse effects of transfusion of blood products on
      morbidity and mortality associated with cardiac surgery and anesthesia.

PMID- 15583790
TI  - Does gender influence the likelihood or types of complications following cardiac
      surgery?
AB  - Over 410,000 cardiac surgeries are performed in American women each year. Women
      having coronary artery bypass graft (CABG) and valve surgery do so at an older
      age and with more cardiovascular risk factors than men. Women's smaller body size
      may also increase risk by increasing the technical difficulty of surgical
      procedures. Female CABG patients appear to have higher perioperative mortality
      and cardiac morbidity, although studies of neurologic outcomes in female CABG
      patients have produced equivocal findings. Women undergoing CABG tend to consume
      more hospital resources than men do in terms of blood transfusion, mechanical
      ventilation, and length of intensive care unit and overall hospital stay. With
      regard to valve surgery, women appear to have worse outcomes than men if the
      surgery is combined with a CABG operation. Women and men undergoing isolated
      aortic valve surgery have similar mortality, but little is known about gender
      differences in mitral and tricuspid valve surgery outcomes. Women who require
      heart transplantation tend to have idiopathic cardiomyopathy rather than the
      ischemic cardiomyopathy that is more common in male heart transplant candidates.
      Although female heart transplant recipients seem to have a stronger immunologic
      response after transplantation, which manifests in more frequent acute rejection
      episodes, it is not clear whether this increases women's mortality risk. Men
      appear to have a greater incidence of posttransplant vasculopathy than women.
      Further research is needed to identify risk factors for perioperative morbidity
      and mortality in women undergoing cardiac surgery and to develop medical
      interventions to mitigate these risks.

PMID- 15583791
TI  - Predictive genomics of adverse events after cardiac surgery.
AB  - Significant, yet highly individual, thrombotic and inflammatory responses to
      surgery provide an excellent opportunity for insight into the genomic impact upon
      a patient's postoperative course. Cardiac surgery elicits the most profound
      perioperative disturbance and is associated with the highest incidence of adverse
      outcomes of any elective surgical procedure. Thus, cardiac surgical patients are
      an ideal population in which to evaluate the influence of complex traits on
      perioperative morbidity and mortality. This review describes the application of
      fundamental genetics upon the occurrence of adverse outcomes after cardiac
      surgery and cardiac transplantation. Specific emphases include a brief primer of
      the principles of genetics concentrating on the effects of variation within the
      human genome upon clinical outcomes and the differences between so-called
      Mendelian traits and complex traits. Four important clinical diseases dealt with
      in this review as examples of the impact of genetic factors on clinical outcomes
      are the genetics of heparin-induced thrombocytopenia, heart transplantation
      rejection and vasculopathy, atrial fibrillation, and infection.

PMID- 15583792
TI  - Acute lung injury and acute respiratory distress syndrome after pulmonary
      resection.
AB  - The occurrence of acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) after thoracic surgery are perplexing and persistent problems. Variously
      described as postpneumonectomy pulmonary edema, noncardiogenic pulmonary edema,
      and postlung resection pulmonary edema, ALI and ARDS may be considered a single
      entity, with ALI being the less severe form of ARDS. It is characterized by the
      acute onset of hypoxemia with radiographic infiltrates consistent with pulmonary
      edema, without elevations in the pulmonary capillary wedge pressure. Although
      this syndrome does not occur frequently and is usually without identifiable
      cause, the mortality is high. However, the phenomenon has not been rigorously
      studied owing to the low incidence, with primarily retrospective case series
      reported. Thus, the nomenclature, risks, and pathogenesis are not well defined.
      Interest in this syndrome has recently been renewed as the rate of other
      perioperative complications has declined. ALI/ARDS is reviewed with a focus on
      potential etiologies and the spectrum of available interventions.

PMID- 15583793
TI  - Complications of major aortic and lower extremity vascular surgery.
AB  - Atheromatous disease and invasive intervention of the aortoiliac and distal
      arteries are common. Morbidity and mortality have been reduced through
      understanding and management of patient risk factors. Complications of this form
      of treatment affect all organ systems; mortality is most frequently caused by a
      cardiovascular complication (eg, myocardial infarction). Infection, leading to
      aortoenteric fistula is a dreaded complication, and paraplegia, though rare, is a
      devastating outcome. Multiorgan failure and death may result from a systemic
      inflammatory response syndrome. Vascular surgery for infrainguinal disease also
      has a significant cardiovascular complication rate. Resulting complications may
      affect all organs; loss of an extremity may occur. The first part of this article
      reviews perioperative and postoperative complications of open aortic repair and
      lower-extremity revascularization and addresses the issue of regional anesthesia
      for major vascular surgery. The second part reviews endovascular aortic repair
      (EVAR). EVAR is a new intervention that combines surgery and radiology.
      Complications of EVAR are similar to open repair, but early results suggest they
      may be less frequent. New technology leads to new complications; endoleaks,
      migration of the endoprosthesis, and surgical conversion are unique to EVAR. The
      benefits of EVAR may be less blood loss, shorter hospitalization, and less
      cardiovascular stress; the risks may be aneurysm recurrence, prolonged
      surveillance and repeated secondary procedures. The development of EVAR, the
      complications, and the anesthesia-related concerns of EVAR, including its use in
      management of acute abdominal aortic aneurysm are reviewed.

PMID- 15583794
TI  - Dendritic cells and HNSCC: a potential treatment option? (Review).
AB  - Patient survival in head and neck squamous cell cancer (HNSCC) has not changed
      significantly in many years, despite progress in surgical, radiotherapy and
      chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer
      treatment, aims to prompt or assist the body's immune system to combat the
      disease itself. A number of strategies exist including the use of dendritic
      cells, natural antigen presenting cells capable of stimulating an anti-tumor
      immune response. Encouraging work has been performed using these cells as
      vaccines against a number of tumors especially melanoma. Work with head and neck
      cancer is also encouraging, but less advanced. Dendritic cell presence in head
      and neck squamous cell cancers is associated with an improved prognosis, however
      due to immunosuppression, the exact mechanism of which remains poorly understood,
      these cells do not function efficiently. This prevents the stimulation of an
      effective anti-tumor immune response by the patient and allows tumor growth to
      continue. This review summarises the current level of understanding of dendritic
      cells and their relationship with HNSCC. It briefly summarises work with
      dendritic cells and other cancers where relevant to HNSCC; dendritic cells and
      head and neck cancer; the possible causes of dendritic cell impairment; the
      techniques used to restore their function and the methods used to prime the
      dendritic cells prior to their use as vaccines for the stimulation of an anti
      tumor response.

PMID- 15583795
TI  - Microsatellite instability and expression of mismatch repair genes in sporadic
      endometrial cancer coexisting with colorectal or breast cancer.
AB  - The molecular background of sporadic endometrial cancer coexisting with
      colorectal or breast cancer is not clear. We investigated microsatellite
      instability (MSI) and status of mismatch repair (MMR) gene product, MLH1, MSH2
      and MSH6, in 63 sporadic endometrial cancers coexisting with colorectal or breast
      cancer. Sixteen sporadic endometrial cancers with colorectal cancers (EC), 26
      sporadic endometrial cancers with breast cancer (EB) and 21 endometrial cancers
      without a coexisting cancer (control) were analyzed. EC had the highest frequency
      of MSI among the 3 groups (EC, 69%; EB, 23%; and control, 43%). Incidence of low
      frequency MSI was significantly higher in EC (38%). Among endometrial cancer
      cases diagnosed before age 50, all high-frequency MSI (MSI-H) cases belonged to
      EC. Interestingly, incidence of MSI-H was significantly higher in tamoxifen-non
      treated cases (75%) than that of treated cases (14%). These results suggest that
      alterations in MMR genes appear to be involved in carcinogenesis of EC but seem
      to be uncommon in those of EB. Presence of MSI in sporadic endometrial cancer may
      be a useful marker to predict the risk of colorectal cancer.

PMID- 15583796
TI  - PTEN and p53 abnormalities are indicative and predictive factors for endometrial
      carcinoma.
AB  - PTEN (phosphatase and tensin homologue deleted on chromosome 10) and p53
      alterations were expected to be diversely involved in endometrial carcinogenesis.
      Patients (n=92) with endometrial carcinoma (EC) were analyzed, and PTEN and p53
      were immunostained in the tissue sections. Tumor histology, grade of
      differentiation, presence of endometrial hyperplasia, staining status of PTEN and
      p53 and clinical information were examined. There were 37 cases (40%) negative
      for PTEN staining, which suggests lost or reduced PTEN function. Loss of PTEN
      staining was significantly related to the advanced staging in the grade 1 (G1)
      and grade 2 (G2) endometrioid adenocarcinoma group (p=0.026). Also, 18 cases
      (20%) showed positive staining for p53. p53 staining was largely found in grade 3
      (G3) endometrioid adenocarcinoma and other phenotypes of EC. In the G1 and G2
      group, all 29 cases with reduced PTEN staining showed p53-negative staining
      (p=0.025). In the G3 and others group, 6 of 8 cases with reduced PTEN staining
      showed p53-positive staining. p53-positive staining was associated with a high
      probability of tumor recurrence in the G1 and G2 group (p=0.0234). In contrast,
      in the G3 and others group, p53-positive cases had a low probability of tumor
      recurrence (p=0.0473). Both PTEN and p53 staining may be good indicators of
      clinical stage and probability of tumor recurrence in EC. Reciprocal abnormality
      of p53 or PTEN occurred at an early phase of carcinogenesis, however simultaneous
      abnormality of p53 and PTEN often occurred at the a late phase of carcinogenesis.
      Thus, immunohistochemistry for PTEN and p53 in biopsy specimens of EC can provide
      supportive information for determining a treatment plan.

PMID- 15583797
TI  - Des-gamma-carboxyprothrombin expression in cancer and/or non-cancer liver
      tissues: association with survival of patients with resectable hepatocellular
      carcinoma.
AB  - Des-gamma-carboxyprothrombin (DCP), also known as a protein induced by vitamin K
      absence or antagonist II, is an abnormal prothrombin. The level of serum DCP is
      used in clinical diagnosis and prognosis of patients with hepatocellular
      carcinoma (HCC). Our previous immunohistochemical study showed that DCP is
      expressed not only in cancer tissues but also in the surrounding non-cancer
      tissues of HCC patients. However, clinical significance of DCP expression in non
      cancer tissues of HCC patients remains unclear. In this study, we examined the
      relationship between histochemical expression of DCP in cancer and/or non-cancer
      tissues and the clinical outcome of the HCC patients. A retrospective study was
      performed of 132 patients each with a single primary HCC nodule. Expression of
      DCP in tissues was evaluated with immunohistochemical staining using anti-DCP
      antibody (MU-3). Serum DCP levels were determined using enzyme immunoassay with a
      double antibody sandwich system. Experimental and clinical data were processed by
      univariate and multivariate statistical analyses. DCP expression, even if it was
      observed only in non-cancer tissues, was related to poorer prognosis. Univariate
      and multivariate analyses showed that DCP expression in cancer and/or non-cancer
      tissues was a significant prognostic factor. Furthermore, the combined evaluation
      of tissue DCP expression and serum DCP levels showed that prognosis was poorest
      for patients showing positive tissue DCP expression and high levels of serum DCP.
      These results suggest that immunohistochemical evaluation of DCP expression not
      only in cancer but also in non-cancer tissues serves as a valuable factor in the
      prognosis of HCC patients and that the combined evaluation of tissue DCP
      expression and serum DCP level will be more valuable than either factor alone in
      the effective treatment and prognosis.

PMID- 15583798
TI  - Somatostatin receptor scintigraphy in metastatic breast cancer patients.
AB  - The purpose of this study was to evaluate the efficacy of somatostatin receptor
      scintigraphy (SRS) in imaging metastases in patients with advanced breast cancer
      (BC), and assess the relationship between exposure to chemotherapy and
      hormonotherapy with overexpression of somatostatin receptor (SS-R) on the breast
      cancer cell surface. Twelve patients with metastatic breast cancer were
      intravenously (i.v.) injected with In-111 pentatreotide (120 MBq). Early and
      later images were obtained with a double-head gamma camera equipped with medium
      energy collimators. SPECT was performed when needed. Imaging results were
      compared with computed tomography and bone scan. Uptake levels were evaluated by
      site-specific visual analysis. Metastatic breast cancer can be visualized with
      SRS. Global sensitivity of imaging was 80% and specificity for correct prediction
      of tumor absence was 100%. Sensitivity was significantly higher for bone and lung
      metastases. SRS results related to the expression of SS-R on metastatic cell
      surfaces did not evidence a relationship with the biologic characteristics of the
      primary BC and drug exposure. In our series, SRS quantitative analysis
      demonstrated that tumor metastases differ greatly in uptake levels. Fifteen
      percent of metastatic sites in our series showed strong uptake. Our data support
      the important specificity of SRS in identifying BC metastases, mostly in cases of
      bone and lung disease, as well as the role of SRS in predicting responsiveness of
      metastatic BC cells to treatment with somatostatin analogues (SS), when SS-Rs are
      overexpressed on cell surfaces. If our results are confirmed in large scale
      studies, SRS shows the potential to treat selected patients with overexpressed SS
      R on their tumoral cells with designed target therapies with SS analogue.

PMID- 15583799
TI  - Carcinoma cell-specific Mig-7: a new potential marker for circulating and
      migrating cancer cells.
AB  - Identification of genes that are expressed in a cancer cell-specific manner can
      provide markers for detection, diagnosis, and disease progression. We have
      previously reported that receptor tyrosine kinase ligands in concert with
      ligation of alphavbeta5 integrin induce expression of Mig-7 restricted to
      carcinoma cells. Because of this highly specific expression, we hypothesized that
      Mig-7 could be used as a marker of occult tumor cells. The objective of this
      study was to begin to test this hypothesis by generating Mig-7 specific antisera
      and RT-PCR methods for detection of Mig-7 expression in tissues and blood from
      cancer patients as compared to those from normal subjects. By
      immunohistochemistry and by RT-PCR, we detected Mig-7 mRNA in lymph nodes from 7
      out of 9 (77.8%) endometrial carcinoma xenograft mice but not from any of the 5
      negative control animals. Mig-7 expression was more specific than Met expression,
      the RTK that binds Scatter factor and is used as a marker of poor progression, in
      endometrial carcinoma as compared to normal endometrial tissue samples. In 87.3%
      of tumors from various tissues including breast, lung, colon and ovary, we
      detected Mig-7 expression. Blood samples from untreated metastatic cancer
      patients also displayed Mig-7 mRNA in contrast to a lack of expression in
      chemotherapy treated or normal individuals. In conclusion, we report the first
      immunohistochemical and RT-PCR assays for Mig-7 and discuss its highly specific
      localization to cancer cells in contrast to an absence in normal cells. Our
      preliminary data indicate that Mig-7 may be a potential early marker of migrating
      and circulating carcinoma cells.

PMID- 15583800
TI  - Effects of triple therapy with octreotide, galanin and serotonin on a human colon
      cancer cell line.
AB  - Human colon cancer cells were implanted subcutaneously into nude mice. After 12
      days, the animals were divided into two groups. The first group received 40
      microg/kg body weight of octreotide, galanin and serotonin via an
      intraperitoneally implanted pump. The second group received sterile saline only.
      Treatment lasted for 14 days. The volume and weight of the tumours in treated
      mice tended to decrease, though not with statistical significance. The
      proliferation index and the number of tumour blood vessels was significantly
      reduced in the mice given triple therapy. The apoptotic index, as detected by
      TUNEL method and monoclonal anti-poly (ADP-ribose) polymerase, was significantly
      higher in the treated mice. Though the results of this investigation are
      promising, it is uncertain as to what use the present findings may imply for the
      treatment of patients with colorectal cancer.

PMID- 15583801
TI  - Ursolic acid induces Bax-dependent apoptosis through the caspase-3 pathway in
      endometrial cancer SNG-II cells.
AB  - The goal of this study was to examine the effect of ursolic acid, a pentacyclic
      triterpenoid compound, on growth of the endometrial cancer cell line SNG-II. We
      found that ursolic acid strongly inhibited the growth of SNG-II cells in a dose-
      and time-dependent manner. Morpholgical changes characteristic of apoptosis were
      observed in treated cells, such as the presence of apoptotic bodies and
      fragmentation of DNA into oligonucleosomal-sized fragments. We also investigated
      the active forms of caspase-3, -8 and -9 in ursolic acid-treated SNG-II cells. At
      25 and 50 microM strength, ursolic acid induced marked increases in caspase-3
      activity to approximately 5-fold that of control cells. Levels of cleaved caspase
      3 increased in a time- and dose-dependent manner. Activation of caspases also led
      to the cleavage of target proteins, such as PARP. Ursolic acid treatment also
      resulted in a cleavage of poly (ADP-ribose) polymerase in a dose-dependent
      manner. Testing whether caspase-3 activation and DNA polymerase activity were
      inhibited by addition of Ac-DEDV-HCO during ursolic acid treatment showed that 50
      microM Ac-DEDV-HCO inhibited caspase-3 activity in treated cells. Although DNA
      fragmentation was observed after ursolic acid treatment, DNA fragmentation did
      not occur in SNG II cells treated with both Ac-DEDV-HCO and ursolic acid. Because
      some researchers have suggested that mitochondrial pathways are involved in
      ursolic acid-induced apoptosis secondary to induction of mitochondrial cytochrome
      c release, we studied mitochondrial events in ursolic acid-induced apoptosis in
      these cell lines. After ursolic acid treatment, the anti-apoptotic Bcl-2 protein
      decreased and Bax expression was enhanced. Our results indicated that ursolic
      acid induced apoptotic processes in the endometrial cancer SNG-II cell line
      through mechanisms involving mitochondrial pathways and Bcl-2 family proteins.

PMID- 15583802
TI  - Prognostic significance of cytoplasmic macrophage migration inhibitory factor
      expression in patients with squamous cell carcinoma of the head and neck treated
      with concurrent chemoradiotherapy.
AB  - The macrophage migration inhibitory factor (MIF) is known to be a proinflammatory
      cytokine as well as a tumor growth regulator. Although the positive and negative
      effects of the MIF on tumor cell growth have been reported, the exact role of the
      MIF in tumorigenesis remains ambiguous. We examined the expression of the MIF
      protein in tumor specimens obtained from 50 head and neck squamous cell carcinoma
      (HNSCC) patients treated with concurrent chemoradiotherapy (carboplatin, 100
      mg/m2), 4-7 times every week; a total radiation therapy dose of 65-75 Gy over 6.5
      7.5 weeks, and determined whether the MIF level is related to clinical outcomes
      of these patients. Immunostaining with an MIF specific antibody was performed in
      formalin-fixed, paraffin-embedded specimens. The MIF protein was expressed to
      various extent in the tumor tissue specimens from the HNSCC patients. Prognostic
      analysis using the Kaplan-Meier method with regard to the MIF expression revealed
      that the patients with the MIF-negative tumors had a worse prognosis when
      compared to those with the MIF expression. The results of this study suggest that
      the intratumoral MIF expression has a prognostic value in HNSCC patients
      administered concurrent chemoradiotherapy.

PMID- 15583803
TI  - Successful laparoscopic radiofrequency ablation of hepatocellular carcinoma
      adhered to the mesentery after transcatheter arterial embolization.
AB  - A 54-year-old male with hepatocellular carcinoma (HCC) underwent transcatheter
      arterial embolization (TAE) at a nearby hospital. He was then referred to our
      hospital for the purpose of additional treatment of HCC. Because TAE was not a
      complete therapy and HCC was growing and protruding from the left lobe of the
      liver, laparoscopic radio-frequency ablation (RFA) was chosen for the treatment
      of HCC. After inserting a laparoscope into the abdominal cavity, it was observed
      that HCC unexpectedly adhered to the mesentery as a result of TAE performed
      previously. After cutting off the adhered mesentery and removing it from the
      tumor, the combination therapy of percutaneous ethanol injection and RFA (PEI
      RFA), developed at our department, was performed on the tumor. The tumor was
      successfully abrogated by PEI-RFA and the sufficient safety margin was confirmed
      by computed tomography after the treatment.

PMID- 15583804
TI  - Adenovirus-mediated gene transfer into rat livers: comparative study of
      retrograde intrabiliary and antegrade intraportal administration.
AB  - To examine the feasibility of liver-directed in vivo gene therapy, we
      administered recombinant adenoviruses carrying a reporter lacZ gene retrogradely
      into the common bile duct of rats, as well as antegradely into the portal vein.
      Transduction efficiency of the lacZ gene in the liver was estimated not only
      histochemically by X-gal staining, but also quantitatively by a chemiluminescent
      reporter gene assay. Retrograde infusion of adenoviruses into the common bile
      duct was shown to successfully induce transgene expression in the liver.
      Transduction efficiency induced by intrabiliary adenoviral administration was not
      significantly different from that induced by intraportal adenoviral
      administration. Although transgene expression induced not only by intraportal,
      but also by intrabiliary adenoviral administration was observed predominantly at
      periportal areas, a considerable number of cells expressing the transgene were
      detectable even in lobular and centrilobular areas. Mild infiltration of
      inflammatory cells into the liver and mild hyperplastic changes of hepatocytes
      were observed after intrabiliary and intraportal adenoviral administration.
      However, hepatic damage estimated pathologically was not substantial.
      Furthermore, although intrabiliary and intraportal adenoviral administration
      resulted in very mild elevation of liver-related serum biochemical parameters,
      apparent complications were not observed in any rats. Our results demonstrated in
      the present study suggest that retrograde administration of adenoviruses into the
      common bile duct can induce efficient transgene expression in the liver without
      causing severe adverse effects, supporting the feasibility of adenovirus-mediated
      gene transfer into the liver in clinical settings by means of endoscopic
      retrograde cholangiography.

PMID- 15583805
TI  - Gene expression profiles correlate with the morphology and metastasis
      characteristics of renal cell carcinoma cells.
AB  - Renal cell carcinoma (RCC) shows various clinical behaviors, and currently
      surgical modalities are the only effective therapy against this cancer. To
      discern the genomic background affecting clinical characteristics such as
      metastasis, we analyzed the gene expression profiles of the RCCs by DNA
      microarray using cell lines originating from primary or metastatic lesions. RNA
      was extracted from ten SKRC RCC cell lines and gene expression profiling was
      performed using a cDNA microarray of nearly 4,000 human cDNA clones. We compared
      the gene expression profiles between these SKRC cell lines and the normal renal
      proximal tubular cell line and among SKRC cell lines that showed different
      characteristics. The clustering of the selected 62 genes revealed similar
      profiling patterns between SKRC-17 and SKRC-29 cells that were derived from
      metastatic RCC lesions. Another cell line from a metastatic lesion, SKRC-52, with
      a unique spindle-shaped morphology, had a different pattern of expression
      profiling from the other cell lines. We found several genes up-regulated in the
      cell lines from metastatic lesions; transgelin, which is reportedly involved in
      cell proliferation and migration, was up-regulated in SKRC-52. The unique
      profiling pattern of gene expression clearly correlated with cell morphology and
      metastatic potential. Such profiling might contribute to identifying the genes
      involved in the clinical characteristics of RCC.

PMID- 15583806
TI  - Inhibin/activin subunits (inhibin-alpha, -betaA and -betaB) are differentially
      expressed in human breast cancer and their metastasis.
AB  - Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH
      alpha) and one of two possible beta-subunits (INH-betaA or -betaB). Aims of this
      study were to determine the frequency and tissue distribution of INH-alpha, 
      betaA and -betaB in breast cancer tissue. Paraffin-fixed ductal carcinoma in situ
      (DCIS; n=7), invasive ductal carcinomas without lymph node metastases (IDC; n=8),
      infiltrating ductal carcinomas with their lymph node metastases (IDC/LN; n=8),
      primary ductal carcinomas with their subsequent recurrence (n=7) were analyzed by
      immunohistochemical means with monoclonal antibodies against inhibin-alpha, 
      betaA and -betaB subunits. INH-alpha was observed in DCIS (5/7), while its
      expression was significantly higher in DCIS than IDC (1/7; p<0.05) and IDC/LN
      (0/8; p<0.005) and recurrent breast cancer tissue (0/7; p<0.005). The INH-betaA
      subunit was also demonstrated in all DCIS cases with a significantly higher
      intensity compared to IDC (p<0.05), IDC/LN (p<0.01) and primary carcinoma with
      subsequent recurrence (p<0.05). INH-betaA expression was significant higher in
      primary tumors with subsequent recurrence compared to IDC/LN (p<0.05). The
      metastatic lymph nodes expressed the lowest inhibin-betaA compared to all other
      groups (p<0.01). INH-betaB was also demonstrated in all mammary carcinoma
      tissues, but without any statistical differences. The differential expression of
      INH-alpha in DCIS might suggest a function as a tumor suppressor in breast
      tissue, suggesting a useful marker for recognizing patients with subsequent risk
      of developing invasive ductal cancer. The higher INH-betaA expression in DCIS
      than invasive cancer suggests an important role in mammary carcinogenesis.
      Interestingly, primary breast tumor with a subsequent recurrence expressed a
      higher intensity of the inhibin-betaA subunit, suggesting an important role in
      metastatic pathogenesis, and utilization as a tumor marker. The immunoreactivity
      of inhibin-betaA was significantly higher in DCIS than invasive ductal
      carcinomas, suggesting an important role in mammary carcinogenesis. The
      metastatic lymph nodes expressed lower INH-betaA and -betaB than the primary
      tumor, which might be the cause of less differentiated and aggressive tumor cells
      within the primary tumor. Therefore, inhibin/activin subunits might be useful
      prognostic markers for breast cancer.

PMID- 15583807
TI  - Anti-carcinogenic and anti-metastatic properties of indole-3-carbinol in prostate
      cancer.
AB  - Indole-3-carbinol (I3C), a compound present as glucobracissin in cruciferous
      vegetables has anticancer activities which is in line with some of the
      epidemiological evidence that suggests a beneficial effect of consumption of
      cruciferous vegetables on cancer incidence and progression. The precise target of
      indole-3-carbinol has not been determined. We examined the effect of I3C on
      prostate cancer in a well-defined R3327 model using Copenhagen rats and the
      transplantable cell line, MAT-LyLu. This cell line derived from a tumor in
      Copenhagen rats is androgen independent and metastasizes to the lung and lymph
      nodes. Tumors were induced in Copenhagen rats by injecting MAT-LyLu
      subcutaneously and the animals treated with I3C that was administered either
      intraperitoneally or intravenously, in order to achieve maximal systemic
      exposure. This was a departure from the traditional chemopreventive route of
      indole-3-carbinol where the compound was incorporated in the diet. Our results
      indicate that I3C inhibited the incidence, growth and metastases of MAT-LyLu
      cells and both i.p. and i.v. injections of I3C were equally effective.
      Statistical analysis (Kaplan-Meier curves) clearly indicates a tumor-free and
      overall survival benefit as a result of treatment with I3C. These studies show
      for the first time that I3C in an injectible form has anti-prostate cancer
      activity.

PMID- 15583808
TI  - Usefulness of digital subtraction imaging with Levovist in the diagnosis of
      hepatocellular carcinomas.
AB  - To classify hepatocellular carcinoma (HCC) based on the findings of digital
      subtraction imaging (DSI) and to compare DSI against other diagnostic imaging
      modalities to assess its reliability DSI was performed in 68 patients with HCC
      (72 nodules) and the enhancement patterns of blood flow in the tumor were
      assessed during the early phase, the portal phase and the late phase. In
      addition, the findings obtained by DSI were compared with those obtained by
      helical CT, digital subtraction angiography (DSA), CO2 angiography and CT during
      arterial portography (CTAP). Of the 72 nodules, blood flow was detected in 64
      (88.9%) by early-phase DSI, in 61 (84.7%) by helical CT, in 62 (86.1%) by DSA and
      in 67 (93.1%) by CO2 angiography. Early-phase DSI did not demonstrate
      hypervascular enhancement in 8 HCC nodules (16.7%). These included 5 nodules in
      which other diagnostic imaging modalities also failed to identify tumor blood
      vessels and 3 nodules located in deep regions 87.5 mm or more from the body
      surface. With regard to these 5 nodules (10.4%) in which tumor vessels were not
      visualized during the early phase, late-phase DSI demonstrated relatively poor
      enhancement compared with normal hepatic parenchyma. Such late-phase defects in
      tumor enhancement were observed in 69 nodules (95.8%). DSI demonstrated
      characteristic findings of HCC enhancement during the early phase, the portal
      phase and the late phase, permitting classification of HCC to be performed.

PMID- 15583809
TI  - Bis(ethyl)norspermine potentiates the apoptotic activity of the pure antiestrogen
      ICI 182780 in breast cancer cells.
AB  - We studied the effects of ICI 182780 and bis(ethyl)norspermine (BE-3-3-3) on cell
      growth and apoptosis of estrogen receptor-positive MCF-7 breast cancer cells.
      Combination treatment with 100 nM ICI 182780 and 5 microM BE-3-3-3 for 6 days
      inhibited cell growth by 74.3+/-8.4% in MCF-7 cells, compared to that of 25.4+/
      5.8 and 45.8+/-12.2%, respectively, when ICI 182780 and BE-3-3-3 were used as
      single agents. Treatment with 100 nM ICI 182780 and 5 microM BE-3-3-3 as single
      agents resulted in 9.1+/-1.0% and 35.1+/-4.5% apoptosis, respectively, as
      measured by APO-BRDU assay. When ICI 182780 and BE-3-3-3 were used in
      combination, the percentage of apoptosis was 60.6+/-3.8%. Improved efficacy of
      ICI 182780 and BE-3-3-3 combination on growth inhibition was observed for T-47D
      cells also. Western blot analysis showed that combinations of ICI 182780 and BE-3
      3-3 caused down-regulation of the anti-apoptotic Bcl-2 and Bcl-XL proteins and
      increased the level of the pro-apoptotic Bax protein. Combination treatment also
      increased caspase-8 activation. Analysis of polyamine levels 48 h after
      combination treatment showed that spermidine and spermine levels were down
      regulated significantly. These studies indicate a potentially effective
      combination strategy for breast cancer treatment. Our results also link the down
      regulation of polyamine pathway to apoptotic cell death and regulation of
      mediators of cell death.

PMID- 15583810
TI  - Altered N-glycosylation in CD45 and regulatory roles of altered N-glycosylation
      in galectin-1-induced growth inhibition in human diffuse large B cell lymphoma.
AB  - Beta1-6 branching of L-PHA reactive oligosaccharides, one of the N-glycan
      structures, plays an important role in the biological behavior of various tumor
      cell lines. We reported previously that the expression of L-PHA reactive
      oligosaccharides was closely associated with the prognosis of patients with human
      diffuse large B cell lymphoma (DLBCL). In the present study, by Western blotting,
      we analyzed the N-glycosylation patterns in CD45 having L-PHA reactive
      oligosaccharides. In two cases of DLBCL which do and do not express non
      sialylated L-PHA reactive oligosaccharides CD45 was found to be about 180-210 kDa
      and 180-200 kDa, respectively. Furthermore, after endoglycosidase F3 treatment
      the CD45 in both cases was found to be 190 or 160 kDa. Therefore, the differences
      in CD45 molecular weight between the two cases is due to differences in the
      amount of N-glycosylation. To clarify the biological functions of CD45 N-glycans
      in DLBCL, we analyzed the antiproliferative effects on human lymphoma cells of
      bovine galectin-1 (beta-galactoside-binding lectin-1), which reacts with CD45 N
      glycans. Bovine galectin-1 stimulation of the DLBCL cell line HBL-2 resulted in
      inhibition of its growth in vitro. Swainsonine (SW) is a potent inhibitor of
      alpha-mannosidase II, which catalyzes the synthesis of complex type N-linked
      oligosaccharides. Reduction in expression of N-linked oligosaccharides, including
      L-PHA reactive oligosaccharides, on the cell surface by SW treatment prevented
      the growth inhibition of HBL-2 cells by galectin-1. On Western blots one 190 kDa
      isoform of the three CD45 isoforms which have N-linked oligosaccharide ligands
      for galectin-1, was detected with a reduction in molecular weight of about 5 kDa
      after SW treatment. These data suggested that the amount of CD45 N-glycans is
      reduced by SW treatment, and that this reduction of N-glycans prevents the
      interaction between CD45 and galectin-1. Alteration in N-glycosylation of CD45
      may regulate lymphoma cell growth in DLBCL through the interaction between the N
      glycans of CD45 and galectin-1.

PMID- 15583811
TI  - Clinical relevance of MMP-9, MMP-2, TIMP-1 and TIMP-2 in colorectal cancer.
AB  - The main aim of this study was to evaluate the clinical relevance of Gelatinases
      in colorectal cancer (CRC). Ninety-five CRCs and their paired normal tissues were
      investigated to detect total levels of MMP-9, MMP-2, and the tissue inhibitors
      TIMP-1 and TIMP-2. Also, pro-MMP and MMP activity, and potential associations
      with clinical parameters were estimated. MMP-9, MMP-2 and TIMP-1 levels were
      greater in CRCs than in normal tissues, differences being significant for MMP-9
      and TIMP-1. However, TIMP-2 showed significantly lower levels in tumour samples.
      Moreover, significant differences in the state of activation between gelatinases
      were found. TIMP-1 low levels were significantly associated with poor clinical
      outcome of patients. According to these data, different roles have to be
      attributed to MMP-2 and MMP-9 in CRC progression. Moreover, TIMP-1 level
      evaluation emerges as the main prognostic factor in relation to Gelatinases A and
      B activity in CRC.

PMID- 15583812
TI  - Efficacy of intraperitoneal continuous hyperthermic chemotherapy as consolidation
      therapy in patients with advanced epithelial ovarian cancer: a long-term follow
      up.
AB  - This trial was performed to determine the efficacy and progression-free and
      overall survivals of patients with advanced ovarian cancer who had been treated
      with intraperitoneal hyperthermic chemotherapy (IPHC). Ten patients with advanced
      ovarian cancer participated in this trial and were treated with IPHC. The median
      progression-free and overall survival rates for all patients treated in this
      study were 41.2 and 70.2 months, respectively. Two of ten patients received
      optimal primary cytoreduction surgery followed by IPHC; four of ten, optimal
      interval debulking surgery followed by IPHC; and four of ten, negative second
      look operation followed by IPHC. The groups had 5 and 14.5, 17.75 and 38, and
      82.75 and 130.25 months median progression-free and overall survival rates,
      respectively. Grades 3-4 toxicity included myelosuppresion, and nephropathy was
      detected. One patient required blood transfusions due to grade 4 anemia and
      thrombocytopenia. Another patient developed grade 3 nephrotoxicity but did not
      require continuous hemodialysis. IPHC was feasible, produced manageable toxicity,
      and showed promise for the treatment of advanced ovarian cancer. Negative second
      look laparotomy followed by IPHC was especially effective when consolidation
      intraperitoneal chemotherapy had been indicated. It produced excellent median
      progression-free and overall survival rates.

PMID- 15583813
TI  - Differential expression of metallothionein isoforms in nasopharyngeal cancer and
      inhibition of cell growth by antisense down-regulation of metallothionein-2A.
AB  - Biological functions of metallothionein (MT) proteins which are encoded by 10
      functional MT isoforms, include cell proliferation, differentiation and
      apoptosis. The aim of this study was to compare the relative expression levels of
      functional MT mRNA isoforms in three nasopharyngeal cancer (NPC) cell lines with
      laryngeal carcinoma and embryonic lung cell lines by quantitative real-time RT
      PCR. All the NPC lines exhibited expression of the MT-2A transcript, whereas the
      MT-1E isoform was expressed in well differentiated HK1 and moderately
      differentiated TW01 but not in poorly differentiated CNE2 cells. Interestingly,
      TW01 and HEp-2 laryngeal cancer cells exhibited similar expression profiles with
      both MT-1E and MT-2A isoforms being detected at levels below those of MRC-5
      embryonic lung fibroblasts. Functional studies of the MT-2A isoform by down
      regulating expression of this gene with MT-2A antisense oligonucleotide in CNE2
      cells, showed a reduction in cell viability and proliferation. These findings may
      provide valuable information in the search for novel therapeutic strategies
      against NPC.

PMID- 15583814
TI  - Resveratrol inhibits cell cycle progression in U937 cells.
AB  - Resveratrol, a naturally occurring stylbene present in grapes, is proposed to be
      responsible for the positive effects of red wine consumption on cardiovascular
      diseases (French paradox). In recent years this molecule has also been proposed
      as a cancer chemopreventive agent. The aim of the present study was to
      investigate the mechanisms by which resveratrol inhibits tumor growth. For this
      purpose, U937 cells were exposed to resveratrol at concentrations usually present
      in red wine, and the effects on proliferation, death and cell cycle machinery
      were assessed. The U937 cell growth was impaired due to reduced cell
      proliferation, without significant induction of apoptosis. This anti
      proliferative effect is associated with modulations in the pattern of DNA
      distribution, with a reduction of G0/G1, particularly G2-M peaks and accumulation
      in the S phase of the cell cycle. This result was confirmed by the observation
      that the rate of [3H]-thymidine incorporation into DNA was significantly reduced
      in resveratrol-treated U937 cells. Consistent with this observation, in the same
      experimental conditions, the activity of ribonucleotide reductase, an enzyme
      critically involved in the process of DNA duplication, decreased. The altered
      progression in the cell cycle could depend on modulations in the activity of
      cyclin dependent kinases and their inhibitors. After exposure of U937 cultures to
      resveratrol, the expression of cyclins A and E, as well as that of CDK2
      increased, while that of p21CIP was significantly reduced. The data shown in this
      report suggests that the prevention of cancer development exerted by resveratrol
      may result from modulations of molecules involved in the regulation of cell cycle
      progression, which block the cells at the S phase checkpoint.

PMID- 15583815
TI  - Highly specific overexpression of the transcription factor SOX11 in human
      malignant gliomas.
AB  - Malignant glioma comprises the majority of primary human brain tumors with 16,800
      new cases reported each year in the USA. Its prognosis remains dismal despite
      numerous attempts to improve conventional therapeutic modalities. Therefore, much
      effort is devoted to the exploration of alternative forms of treatment such as
      immunotherapy. The identification of potential target structures highly
      overexpressed in brain tumors is a crucial prerequisite for the activation of the
      immune defense against malignant glioma cells. By screening an expression
      database for genes highly expressed in glioblastoma multiforme (GBM), we
      identified the Pit-Oct-Unc (POU) cooperating transcription factor SOX11 that is
      known to be crucially involved in brain development. Analysis of the expression
      pattern of SOX11 in different normal adult and fetal tissues by multiple tissue
      dot blot and by a highly sensitive quantitative PCR assay confirmed the selective
      overexpression of SOX11 in fetal brain tissue. Examination of tissue specimens
      obtained from malignant gliomas and from normal brain by quantitative real-time
      PCR (Q-RT-PCR) revealed upregulation of SOX11 in almost all tumor samples (15/16)
      as compared to the pooled normal brain. Seventy-five percent of the tumor samples
      (12/16) showed a 5- to more than 600-fold overexpression. We conclude that, after
      downregulation of SOX11 in the adult brain, its expression is reactivated during
      tumorigenesis and that SOX11 therefore represents a promising novel molecular
      target for adjuvant therapy of malignant gliomas.

PMID- 15583816
TI  - Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with
      non-small cell lung cancer.
AB  - Thymidine kinase 1 (TK1) is a pyrimidine metabolic pathway enzyme involved in
      salvage DNA synthesis and thus, a cell cycle-dependent marker. We have developed
      anti-TK1 monoclonal/polyclonal Abs raised against a 15-amino acid synthetic
      peptide (KPGEAVAARKLFAPQ) corresponding to part of the C-terminus of human TK1.
      These Abs are useful for both serological and immunohistochemical detection of
      TK1 in a number of cancer diseases. In this study we examined TK1 concentration
      in serum (STK1) in 250 preoperative non-small cell lung cancer patients (NSCLC),
      including 188 non-metastatic (group M0) and 62 metastatic patients (group M1).
      Serum from 16 healthy individuals was used as controls. The concentration of STK1
      of preoperative NSCLC patients was significantly higher than STK1 of healthy
      individuals (p<0.0001). In group M0, preoperative STK1 concentration was
      significantly higher in patients of tumour size T2, as compared to tumour size T1
      (p=0.042), and in T3-T4, as compared to T1-T2 (p=0.01). No significant difference
      in STK1 concentration between patients of tumour stage I and stage II (p=0.057)
      were found, but significantly higher STK1 concentration in patients of stage III,
      as compared stage I-II (p=0.025). No significant difference of STK1 concentration
      were found in patients of group M1 concerning tumour size or tumour stage, or
      between patients with adenocarcinomas (AC) and squamous cell carcinomas (SCC). We
      studied the changes of STK1 concentration individually one month after operation
      in metastatic subjects (group M1, n=19) and in tumour-free subjects (group M0,
      n=38). In the M0 group, the concentration of STK1 one month after operation was
      significantly decline by 45%, when comparing to concentrations of STK1
      preoperative (p<0.001). In the group M1, however, no significant decrease in STK1
      concentrations were found one month after operation. We conclude that STK1 has
      prognostic value and is a reliable marker for monitoring the response to surgery
      of NSCLC patients.

PMID- 15583817
TI  - Circulating soluble tumour necrosis factor receptors in patients with
      epidermodysplasia verruciformis as compared to patients with cutaneous tumours in
      the general population.
AB  - Soluble tumour necrosis factor receptors type I and II (sTNF-RI and II) were
      evaluated in sera from patients with epidermodysplasia verruciformis and patients
      with cutaneous warts, actinic keratoses, squamous cell carcinomas or basal cell
      carcinomas by specific enzyme-linked immunobiological assays. In patients with
      widespread epidermodysplasia verruciformis lesions, the levels of both sTNF-Rs
      were in normal range. Both types of sTNF-Rs were significantly increased in
      patients with warts. The levels of sTNF-RI were significantly increased in
      patients with multiple actinic keratoses, squamous cell carcinoma and basal cell
      carcinoma. Increased levels of circulating sTNF-Rs may facilitate development of
      cutaneous tumours. Normal levels of sTNF-Rs in patients with epidermodysplasia
      verruciformis might, at least partially, contribute to a slow growth and low
      metastatic potential of cancers in these patients.

PMID- 15583818
TI  - Increased systemic efficacy of aphidicolin encapsulated in liposomes.
AB  - Aphidicolin, a tetracyclic diterpene antibiotic produced by Cephalosporium
      aphidicola, is under investigation as anti-cancer drug. Because of its poor
      solubility in water, it cannot be administered directly in vivo. Systemic
      application of aphidicolin glycinate or aphidicolin gamma-cyclodextrin complexes
      resulted in tumour growth inhibition but not in cures. To improve the
      pharmacokinetics, a liposomal preparation of aphidicolin was developed and tested
      in neuroblastoma-bearing (UKF-NB-3) mice. The loading capacity of these liposomes
      was limited. Therefore, 4.5 mg aphidicolin/kg body weight was the maximum
      aphidicolin dose that could be applied as liposomal preparation in this approach.
      Comparison of effects on tumour growth exhibited by aphidicolin liposomes (4.5 mg
      aphidicolin/kg) given for 15 consecutive days to those of gamma-cyclodextrin
      inclusion complexes (15 mg aphidicolin/kg) revealed comparable tumour growth
      inhibition, although aphidicolin concentrations were approximately 3-fold lower.
      This shows that liposomal encapsulation is a promising strategy for the
      improvement of systemic anti-cancer activity of aphidicolin.

PMID- 15583819
TI  - Flow cytometric DNA ploidy in salivary gland tumours.
AB  - This study on 279 tumours of the salivary glands was conducted to analyse whether
      the assessment of DNA ploidy by flow cytometry may assist histopathology in
      discriminating benign from malignant types of tumours. The group of benign
      tumours included 164 pleomorphic adenomas, 51 Warthin's tumours, 7 basal cell
      adenomas, 2 lipomas as well as 5 other different tumours. All of the 229 benign
      tumours were diploid. The malignant tumours consisted of 18 adenoid cystic
      adenomas, 10 mucoepidermoid carcinomas, 5 acinic cell carcinomas, 5 carcinoma in
      pleomorphic adenoma as well as of 12 other malignancies belonging to 7 different
      tumour entities. Twelve of 50 malignant salivary gland tumours were aneuploid.
      There was no significant relationship between the DNA ploidy status and
      histopathological grading, lymph node metastasis and local recurrence
      development, respectively. In three cases which initially were taken for
      pleomorphic adenomas by routine histological examination, aneuploid cell
      populations exposed by DNA flow cytometric analysis gave rise to a closer
      inspection of the suspect lesions. Examination of consecutive slides actually
      revealed small assemblies of carcinoma cells that required a final diagnosis as
      non-invasive carcinoma in pleomorphic adenoma. The most obvious value of DNA flow
      cytometry in salivary gland tumours is thus its contribution to assist
      histopathology in identifying potentially malignant lesions.

PMID- 15583820
TI  - Radiosensitization, after a combined treatment of survivin siRNA and irradiation,
      is correlated with the activation of caspases 3 and 7 in a wt-p53 sarcoma cell
      line, but not in a mt-p53 sarcoma cell line.
AB  - Survivin, a member of the inhibitor-of-apoptosis family is an essential protein
      for regular mitosis and is involved in an anti-apoptotic pathway. In some
      studies, an association between survivin expression and radiosensitivity has been
      described for tumor cells, but the relationship between p53 and survivin
      regarding radioresistance remains to be clarified. In order to increase the
      effect of irradiation on two sarcoma cell lines, A-204 with wt-p53 and US 8-93
      with mt-p53, siRNA was applied to knock down survivin expression. The effects of
      combined treatment of siRNA treatment and irradiation were investigated by
      clonogenic survival assay, measurement of activity of caspases 3 and 7, Western
      blot hybridization for survivin and p53, and morphological analysis of apoptosis.
      Survivin knock down caused radiosensitization in the cell line A-204 (wt-p53)
      with an enhancement factor of 1.8 at 2 Gy (p=0.05) and 2.5 at 4 Gy (p=0.02),
      respectively. No radiosensitization was found in the cell line US 8-93 (mt-p53),
      when clonogenic survival was analyzed. These findings were supported by an
      increase in activity (up to 5.2-fold) of caspases 3 and 7 in cell line A-204 (wt
      p53), but not in cell line US 8-93 (mt-p53) after a combined treatment of siRNA
      and irradiation. Our findings suggest that the wt-p53-caspase pathway is of
      importance for the radiosensitization induced by targeting survivin, which may
      have an impact on future gene therapeutical treatments.

PMID- 15583821
TI  - Neuropeptide-Y and Y-receptors in the autocrine-paracrine regulation of adrenal
      gland under physiological and pathophysiological conditions (Review).
AB  - Neuropeptide-Y (NPY) is a 36-amino acid peptide, which belongs, along with
      peptide YY (PYY), to the pancreatic polypeptide (PP) family. The members of this
      family of peptides act via G protein-coupled receptors (Rs), six subtypes of
      which (from Y1- to Y6-R) have been identified. NPY and PYY preferentially bind
      the Y1-R, Y2-R and Y5-R, while PP mainly acts via the Y4-R. Evidence has been
      provided that the Y3-R is selective for NPY. NPY and Y-Rs are expressed in the
      adrenal gland (preferentially adrenal medulla) and pheochromocytomas, where they
      exert various autocrine-paracrine regulatory functions. Findings indicate that
      NPY is co-released with catecholamines under a variety of stimuli, including
      splanchnic nerve and cholinergic- and nicotinic-receptor activation. NPY, mainly
      acting via the Y1-R, Y2-R and Y3-R, either inhibits catecholamine secretion from
      bovine adrenal chromaffin cells or stimulates catecholamine secretion from
      adrenomedullary cells of humans and rats. NPY inhibits aldosterone secretion from
      dispersed zona glomerulosa (ZG) cells, but this effect has probably to be
      considered non-specific and toxic in nature, since it is obtained only using
      micromolar concentrations of the peptide. In contrast, NPY appears to modulate
      the secretory response of dispersed rat ZG cells to their main agonists (ACTH,
      angiotensin-II and potassium). However, there is indication that the main effect
      of NPY on the ZG in rats is indirect and involves the local release of
      catecholamines, which in turn, acting via beta-adrenoceptors, enhance the
      secretion of aldosterone. The prolonged treatment with NPY is also able to
      enhance the growth of the rat ZG. In contrast, the effects of NPY on
      glucocorticoid secretion from zona fasciculata-reticularis cells are negligible
      and doutbful. The physiological relevance of the effects of NPY on adrenal
      medulla and ZG remains to be addressed by future experimental studies employing
      more selective and potent Y-R antagonists. In contrast, indirect evidence is
      available that endogenous NPY system may play an important role in the modulation
      of adrenal functions under paraphysiological conditions (e.g. it seems to dampen
      exceedingly high responses to stresses). Moreover, it has been also suggested
      that endogenous NPY may be involved in the regulation of blood pressure and in
      the pathophysiology of pheochromocytomas.

PMID- 15583822
TI  - Angiogenesis in hereditary hemorrhagic telangiectasia: VEGF165 plasma
      concentration in correlation to the VEGF expression and microvessel density.
AB  - Angiogenesis defines the physiologic process of capillary blood vessel formation.
      It is a multistep process, which is controlled by a large number of pro- and anti
      angiogenic factors. Vascular endothelial growth factors (VEGF) are the best
      characterized pro-angiogenic factors, which play a key role in angiogenesis.
      Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant, multi
      systemic disorder of angiogenesis, clinically characterized by severe and
      recurrent hemorrhages. We assume in HHT patients with increased VEGF plasma
      levels a high VEGF expression also correlates with the degree of microvesssel
      density (MVD). In 41 HHT patients and 47 healthy patients, the VEGF165 plasma
      concentration was determined by standard ELISA technique. Cryostat sections of 13
      HHT patients were immunostained for VEGF and endothelial cells by an anti-vWF
      monoclonal antibody using a standard streptavidinbiotin complex procedure. The
      degree of vessel density was quantified by light microscopy (x200) within 'hot
      spot' areas of the HHT-tissue. All HHT cryostat sections showed a medium to
      strong staining for VEFG compared to healthy control tissue. The VEGF expression
      correlated with the VEGF165 plasma concentration and the mean MVD in HHT
      patients. HHT patients with medium VEGF staining revealed significantly lower
      VEGF165 plasma concentrations and a lower mean MVD (204+/-12 vessels/per
      microscopic field) than HHT patients with strong VEGF staining (327+/-76
      vessels/per microscopic field). High VEGF expression in patients with HHT in
      correlation to their VEGF165 plasma levels and the microvessel density may
      support the theory that VEGF functions as an important regulator and key protein
      of angiogenesis, even in HHT.

PMID- 15583823
TI  - Interferon-alpha gene therapy prevents aflatoxin and carbon tetrachloride
      promoted hepatic carcinogenesis in rats.
AB  - Retrovirus-mediated interferon alpha (IFN-alpha) gene transfer was evaluated with
      regard to its possible protective effects against aflatoxin B1 (AFB1)-initiated
      and carbon tetrachloride (CCl4)-promoted hepatic carcinogenesis in rats. To our
      knowledge, this is the first time an experimental in vivo gene therapy trial was
      conducted in Egypt. Two genes were examined in liver tissue by RT-PCR: the first
      was glutathione-S-transferase placental (GST-P) isoenzyme, as an early marker to
      detect hepatic malignancy; the second was IFN-alpha gene expression to detect the
      efficiency of gene uptake and its persistence after transduction. Forty male
      rats, divided equally into 4 groups, were included in the study: the first group
      was the control; the second group received CCl4 0.2 ml subcutaneously twice
      weekly for 12 weeks and AFB1 0.25 mg/kg body wt intraperitoneally twice weekly
      for 6 weeks; the third group received IFN-alpha (10(8) pfu) intravenously in the
      tail vein prior to the start of CCl4 and AFB1 injections; and the fourth group
      received IFN-alpha (10(8) pfu) by intrahepatic injection under ultrasonography
      guide after termination of the CCl4 and AFB1 injection schedule. The results
      showed that IFN-alpha has a marked and significant protective effect against
      hepatic fibrogenesis as well as hepatic carcinogenesis. Pathological examination
      of liver tissue proved that IFN-alpha minimized both fibrotic and cirrhotic
      processes. The amount of fibrosis was less in both groups receiving IFN-alpha,
      with more protection in the group that received IFN-alpha intravenously prior to
      CCl4 and AFB1. The results of RT-PCR showed that the IFN-alpha gene was
      significantly expressed in both groups receiving IFN-alpha, with a more intense
      expression in the group that received IFN-alpha by intrahepatic injection after
      termination of CCl4 and AFB1 injections. The IFN-alpha gene was detected after
      three months of gene transduction in rats receiving IFN-alpha intravenously prior
      to CCl4 and AFB1 and after one month of gene transduction in the post CCl4 and
      AFB1 rats. IFN-alpha gene was not expressed in the two groups that did not
      undergo gene transfer. Histopathological signs of premalignant macronodules were
      evident in the group receiving CCl4 and AFB1, but not IFN-alpha as well as in the
      group that received IFN-alpha at the end of the experiment. GST-P gene expression
      was also detected in these two groups, confirming early malignant transformation.
      In conclusion, IFN-alpha exerts significant protective effects, but more so when
      the gene is administered before fibrogenic and carcinogenic induction in hepatic
      tissues. IFN-alpha gene therapy may be justified in clinical trials for high-risk
      candidates with hepatic carcinogenesis.

PMID- 15583824
TI  - Distinct expression patterns of alpha1 (IV) and alpha5 (IV) collagen chains in
      cylindroma and malignant cylindroma.
AB  - Cutaneous cylindromas are considered to derive from cells of the sweat gland
      apparatus. The composition of the thick hyaline eosinophilic basement membrane
      (BM)-like zone surrounding epithelial aggregates in cylindromas is similar to
      that of the dermo-epidermal junction. The presence of type IV collagen has been
      documented, but the distribution of the different constitutive a chains of
      collagen IV has not been studied so far. Alterations in the expression of these
      alpha chains have been described in some other conditions including basal cell
      carcinomas, testes with spermatogenic dysfunction and colorectal carcinomas. The
      aim was to study the distribution of the alpha1 (IV) and alpha5 (IV) collagen
      chains in cylindromas and malignant cylindroma, and to compare it with the BM of
      sweat glands. Seven cylindromas and one malignant cylindroma were studied. They
      were formalin-fixed and paraffin-embedded before processing for
      immunohistochemistry. Immunostaining was assessed using the avidin-biotin
      peroxidase technique with antibodies directed to the alpha1 (IV) and alpha5 (IV)
      collagen chains. In all cylindromas, a thin continuous and sharply limited
      immunolabelling for the alpha1 (IV) collagen chain was abutted to the tumoral
      cell aggregates. A speckled immunoreactivity was found in the rest of the hyaline
      sheath. Globular structures encased in the cell aggregates also exhibited a thin
      peripheral rim positive for the alpha1 (IV) collagen chain. The immunoreactivity
      was faint and granular in the center of the globules. With the antibody directed
      against the alpha5 (IV) collagen chain, 3 cylindromas did not show any staining,
      2 cases presented discrete focal positivity in the mid-part of the BM-like zone,
      and 2 cases exhibited a positive staining pattern similar to that observed for
      the alpha1 (IV) collagen chain, but with a focal and more discrete intensity. The
      malignant cylindroma showed a linear immunoreactivity for the alpha1 (IV)
      collagen chain undistinguishable from the pattern seen in the benign cylindromas.
      No immunoreactivity was present for the alpha5 (IV) collagen chain in the
      malignant neoplasm. As reported for other BM components, the expressions of the
      alpha1 (IV) and alpha5 (IV) collagen chains are altered in the BM-like zone
      surrounding the epithelial clumps in cylindromas. The molecular alteration is
      probably related to the ultrastructural particularities of this structure. The
      distinctive patterns of expression of the alpha1 (IV) and alpha5 (IV) collagen
      chains may be related to the histogenic sudoral origin of cylindromas without any
      relationship with the benign or malignant nature of the neoplasm.

PMID- 15583825
TI  - RNA interference-mediated silencing of the p53 tumor-suppressor protein
      drastically increases apoptosis after inhibition of endogenous fatty acid
      metabolism in breast cancer cells.
AB  - Fatty acid synthase (FAS)-dependent endogenous fatty acid synthetic activity is
      abnormally elevated in a biologically-aggressive subset of breast carcinomas.
      Remarkably, tumor-associated FAS hyperactivity represents a novel target for anti
      metabolic therapy because pharmacological inhibitors of FAS are selectively
      cytotoxic for tumor cells, triggering their apoptotic cell death. Since the p53
      tumor-suppressor protein (TP53) is thought to play a novel role in cellular
      responses of a variety of non-genotoxic metabolic stresses, we characterized the
      involvement of TP53 in the response of breast cancer cells to FAS inhibition. MCF
      7 breast cancer cells were selected for study because they have an intact TP53
      pathway and undergo little apoptosis following FAS blockade. Two chemically
      distinct inhibitors of FAS (the natural mycotoxin cerulenin and the novel small
      molecule inhibitor C75) were studied in parallel to provide a broad picture of
      consequences suffered by the loss of FAS function on TP53 signaling. Treatment
      with either cerulenin or C75 induced TP53 protein accumulation at 24 h in MCF-7
      cells. To determine whether the up-regulation of TP53 following exposure to
      cerulenin or C75 was solely due to inhibition of endogenous fatty acid
      metabolism, we first evaluated the cytotoxic response to chemical FAS blockers on
      MCF-7 cells in which FAS gene expression was previously silenced by using the
      highly sequence-specific mechanism of RNA interference. MCF-7 cells became
      insensitive to C75-induced cytotoxicity when the expression of FAS was
      specifically suppressed by targeted knock-down with small interfering RNA
      (siRNA), whereas they partially retained their sensitivity to cerulenin. These
      results demonstrate that C75-induced cytotoxic damage to breast cancer cells is
      closely dependent on its ability to inhibit FAS-catalyzed endogenous fatty acid
      biogenesis, thus ruling out a significant direct effect of C75 on DNA. To
      determine the functional role of TP53 on breast cancer cell survival after FAS
      blockade, we evaluated FAS inhibitor-mediated apoptosis in MCF-7 cells
      transiently transfected with a pool of sequence-specific double-stranded RNA
      oligonucleotides targeting TP53 gene. In these conditions, TP53 protein levels
      were unchanged during the period of FAS-inhibitor exposure. Remarkably, siRNA
      induced silencing of TP53 gene expression did result in a dramatic increase
      (approximately 300%) in apoptotic cell death following exposure to C75.
      Strikingly, there was no apparent relationship between the TP53 mutational status
      and sensitivity to chemical FAS inhibitor in a panel of human breast cancer cell
      lines. However, the degree of TP53 mRNA expression was predictive of sensitivity
      to C75-induced cytotoxicity, with low-TP53 mRNA expressing breast cancer cells
      showing hypersensitivity to FAS blockade. These findings strongly suggest that:
      a) TP53 is a novel molecular sensor of energy imbalance after the perturbation of
      endogenous fatty acid metabolism in breast cancer cells; b) TP53 function closely
      influences the decision between apoptosis and growth arrest following FAS
      blockade; and c) pharmacological inhibitors of FAS activity may be clinically
      useful against breast carcinomas exhibiting mutation or aberrant expression of
      TP53.

PMID- 15583826
TI  - Expression of apoptosis-related proteins in advanced uterine cervical cancer
      after balloon-occluded arterial infusion chemotherapy as an indicator of the
      efficiency of this therapy.
AB  - We previously reported satisfactory therapeutic results of cisplatin-based cyclic
      balloon-occluded arterial infusion chemotherapy (BOAI) as neoadjuvant
      chemotherapy, which enabled treatment by hysterectomy in patients with advanced
      cervical cancer. We also reported expression of apoptosis among these patients
      and determined that the bax gene is related to this apoptosis. In the present
      study, we investigated the relationship between the effectiveness of BOAI therapy
      and expression of apoptosis regulatory genes and proteins in these cases. The
      subjects were 27 women with advanced cervical cancer classified as FIGO
      (International Federation of Gynecology and Obstetrics) stage III or higher who
      were admitted to the Department of Gynecology, Osaka City University Medical
      School Hospital between 2000 and 2003. All patients were treated by BOAI, and
      expression of cancer cell apoptosis was examined by the TUNEL method, expression
      of bax, bcl-2 and bcl-xL proteins were examined by immunohistochemistry, and
      expression of bax, bcl-2 and bcl-xL mRNA was examined by quantitative RT-PCR
      before and 3 days after BOAI. The effectiveness of BOAI therapy was thus
      determined. The 20 patients in whom BOAI was effective showed significantly
      higher expression of the bax protein and gene after BOAI, and cancer cell
      apoptosis was accelerated. On the other hand, the 7 patients in whom BOAI was
      ineffective showed significantly higher expression of the bcl-xL protein and gene
      after BOAI. These results suggest that bax/bcl-xL expression can be used as an
      indicator of the effectiveness of BOAI therapy.

PMID- 15583827
TI  - Expression of thrombospondin-1 in prostate-derived cell lines.
AB  - Thrombospondin-1 (TSP-1) is a multifunctional matricellular glycoprotein involved
      in several mechanisms critical to the formation and progression of solid tumors
      including cell adhesion, proliferation, migration, invasion, and angiogenesis.
      However, work related to TSP-1 expression and functionality in prostate cancer is
      limited. Expression experiments in the present study demonstrated lower
      expression of TSP-1 in the prostate cancer cell lines DU 145 and LNCaP compared
      to SV40-immortalized prostatic epithelial cells PNT 1A. All three cell lines
      expressed the TSP-1 receptor CD36. Exogenously added TSP-1 modulated the cellular
      phenotype of LNCaP cells, which demonstrated decreased proliferation rate and
      partly entered apoptosis. Collectively, these data support the concept that
      partial or complete loss of TSP-1 synthesis may provide tumor cells with a
      proliferation advantage. In addition, TSP-1 located at the border between tumor
      and stroma as observed in primary prostate tumors may act as a barrier of tumor
      growth depending on the TSP-1 receptor repertoire of the tumor cells.

PMID- 15583828
TI  - Expression of matrix metalloproteinase 9 and its regulators in the unstable
      coronary atherosclerotic plaque.
AB  - Unstable coronary syndromes, initiated by rupture of an atherosclerotic plaque,
      may involve the activation of matrix metalloproteinases (MMPs). The regulation of
      MMP activity is complex and involves three steps. First, an inactive pro-MMP is
      transcriptionally regulated, a process that is likely to involve the
      transcription factor activator protein-1 (AP-1) and nuclear factor kappa B (NF
      kappaB). Secondly, the pro-MMP is proteolytically cleaved into an active MMP.
      Plasmin has been suggested to be the major activator of MMPs in vivo. Thirdly,
      the activated MMP can be inhibited by tissue inhibitors of metalloproteinase
      (TIMPs). We investigated if expression of MMP9 and its potential regulators are
      induced in unstable coronary plaques. Atherosclerotic plaques from patients with
      stable (n=22) and unstable (n=39) angina were obtained by directional coronary
      atherectomy and analysed by semiquantitative RT-PCR and immunohisto-chemistry.
      Plasma was collected for ELISA analysis. mRNA for MMP9 as well as plasminogen
      activator inhibitor-1 (PAI-1) was increased in unstable plaques, while tissue
      type plasminogen activator (tPA) expression was similar in stable and unstable
      plaques. Plaques from unstable patients had an increased infiltration of
      macrophages and T-lymphocytes, nuclear localisation of AP-1 and the NF-kappaB
      subunit p65, as well as increased positive immunostaining for MMP9 and tPA.
      Plasma MMP9 antigen was elevated in unstable patients. MMP9 is expressed in the
      unstable coronary atherosclerotic plaque, as are its transcriptional and
      posttranscriptional regulators.

PMID- 15583829
TI  - Hepatocyte growth factor/scatter factor induces VEGF in human external auditory
      canal cholesteatoma cell culture.
AB  - Human external auditory canal cholesteatoma (EACC) is not often seen in
      otolaryngology. Some authors have noted circulatory disorders of the local blood
      vessels as the etiologic factor for establishing EACC. Diminished oxygen supply
      results in the attempt to establish angiogenesis. Hepatocyte growth
      factor/scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF) are
      the most important angiogenic factors in this process. In a recent study we
      described strong expression of VEGF and HGF in EACC. All EACC and normal AMS cell
      cultures were obtained from 5 patients undergoing surgery and used at passage 3.
      After 16 to 72 h of incubation with 20 ng/ml HGF/SF, the expression of the VEGF
      protein in the supernants of the HGF/SF-treated and untreated culture was
      analyzed. EACC-culture cells showed a stronger baseline expression of VEGF. After
      72 h of incubation with 20 ng/ml HGF/SF of HGF/SF, the expression of VEGF in
      normal keratinocytes was 173.4 pg/ml. The expression level of VEGF in the EACC
      culture was 275.73 pg/ml. We observed a 2.5-fold induction of VEGF in EACC after
      72 h, which started with 1.5-fold baseline VEGF concentrations of normal
      keratinocytes. Our analysis showed that, in the EACC culture, VEGF was elevated
      after treatment with HGF/SF. HGF/SF appears to activate cellular pathways
      inducing release of VEGF. After purification, no fibroblasts were present in our
      EACC culture so as to exclude possible paracrine effects by fibroblasts.

PMID- 15583830
TI  - The kinase domain of death-associated protein kinase is inhibitory for
      tubulointerstitial fibrosis in chronic obstructive nephropathy.
AB  - Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-dependent
      serine/threonine kinase that is thought to mediate apoptosis. We have shown that
      the kinase domain of DAPK is crucial for the induction of renal tubular cell
      apoptosis in chronic obstructive uropathy (COU) created by unilateral ureteral
      ligation. DAPK-mutant mice, generated by deletion of 74 amino acids from the
      catalytic kinase domain, were used to investigate the role of the DAPK kinase
      domain in renal fibrosis following COU. Interstitial collagen and alpha-smooth
      muscle actin (alpha-SMA) expressions in situ were compared between obstructed
      kidneys in wild-type and mutant mice. As a result, tubulointerstitial fibrosis,
      as quantified by interstitial collagen expression, was significantly augmented in
      mutant kidneys compared with wild-type kidneys following COU. Furthermore,
      deletion of the kinase domain from DAPK significantly increased the appearance of
      alpha-SMA-positive myofibroblasts in the renal interstitium during COU. Thus, our
      results suggest that the kinase domain deleted by gene targeting plays a
      suppressive role for the development of renal fibrosis through inhibition of the
      tubular epithelial-to-mesenchymal transition in a mouse model of COU.

PMID- 15583831
TI  - Interleukin-1beta and tumor necrosis factor-alpha upregulate interleukin-23
      subunit p19 gene expression in human colonic subepithelial myofibroblasts.
AB  - The recently identified cytokine interleukin-23 (IL-23) consists of p19 and p40
      subunits. The major cellular source of IL-23 is dendritic cells and/or
      macrophages. We investigated the expression of IL-23 p19 mRNA in human colonic
      subepithelial myofibroblasts (SEMFs). p19 mRNA was not expressed in unstimulated
      SEMFs, but IL-1beta and TNF-alpha strongly induced p19 mRNA expression in these
      cells. The effects of IL-1beta were much stronger than those of TNF-alpha. These
      responses were observed in both a dose- and time-dependent manner. Furthermore,
      these cytokines acted synergistically when used in combination. A blockade of NF
      kappaB activation by the overexpression of a stable form of IkappaBalpha
      completely blocked these responses, indicating that the induction of p19 mRNA
      expression by IL-1beta and TNF-alpha was mediated by the NF-kappaB activation
      pathway. In conclusion, this is the first report demonstrating that IL-23 p19
      mRNA is inducible in colonic myofibroblasts by IL-1beta and TNF-alpha. The p19
      expression in these cells might play a role in mucosal immune responses.

PMID- 15583832
TI  - The profile of hMLH1 methylation and microsatellite instability in colorectal and
      non-small cell lung cancer.
AB  - Microsatellite instability (MSI) is caused mainly by dysfunction of hMLH1, where
      aberrant hypermethylation (HM) of its promoter region is involved. Previously, we
      suggested that HM in the proximal region of the hMLH1 promoter plays a critical
      role in progression of gastric cancer with MSI and this specific region should be
      analyzed for diagnostic use of hMLH1 HM. We expanded the analyses of hMLH1 HM and
      MSI phenotype to sporadic colorectal cancer (CRC) and non-small cell lung cancer
      (NSCLC) to further evaluate the diagnostic value of hMLH1 HM. A total of 174 CRC
      and 94 NSCLC samples were used for hMLH1 methylation analysis by real-time
      methylation-specific PCR. Methylation levels were measured in three distinct
      regions of the promoter, designated as hMLH1-A, hMLH1-B, and hMLH1-C from distal
      to proximal. MSI phenotype was determined using five microsatellite markers,
      BAT25, BAT26, D2S123, D5S346, and D17S250. Methylation profile of the hMLH1
      promoter varies between CRC and NSCLC. High methylation levels were observed in a
      group of CRC samples. Consequently, three patterns of methylation in the hMLH1
      promoter regions were found: 1) low methylation level in all regions, 2) high
      methylation level in hMLH1-A with low methylation level in hMLH1-C, 3) high
      methylation level in all regions. In contrast, only one NSCLC showed high
      methylation level in hMLH1-A. Of the 134 CRCs examined, 14 (10.4%) showed MSI
      phenotype. No MSI phenotype was found in the initial 80 NSCLCs analyzed. Eight
      (57.1%) of 14 CRC with MSI showed HM in hMLH1-C, which was linked exclusively
      with MSI phenotype. However, the HM in hMLH1-A or -B was not sufficient for MSI.
      CRC with MSI phenotype was significantly more frequent in older patients and in
      the proximal colon, and was more evident in cases with hMLH1-C HM. The results
      suggested that hMLH1 HM cannot be used as an alternative diagnostic marker of MSI
      phenotype in sporadic CRC and NSCLC. CRC with MSI might have
      clinicopathologically distinct subgroups according to hMLH1-C HM status. The
      observed profiles of hMLH1 methylation and MSI in gastric cancer, CRC, and NSCLC
      were quite different from each other, facilitating the better understanding of
      the pathogenesis of these cancers.

PMID- 15583833
TI  - Role of beta2-chimaerin in the behaviour of murine mammary carcinoma cells in
      response to extracellular matrix components.
AB  - Chimaerins are high affinity receptors for phorbol esters and diacylglycerol
      (DAG), unrelated to the protein kinase C isozymes. These receptors have deep
      implications in tumour biology since they regulate the activity of Rac1, a small
      GTP-binding protein of the Ras superfamily. It has been demonstrated that
      chimaerins have GTPase activating protein (GAP) activity, leading to the
      acceleration of GTP hydrolysis from Rac1 and therefore facilitating the
      transition to its inactive state. Rac regulates various cellular events,
      including gene transcription, cell cycle, adhesion and migration. It has also
      been described that Rac is implicated in the intracellular response to the
      binding of specific extracellular matrix proteins to integrin receptors. In this
      work, we analysed cell morphology, actin cytoskeleton reorganisation and
      metalloprotease (MMP) secretion in response to matrix proteins in mouse mammary
      carcinoma cells transfected with the beta2-chimaerin GAP domain. Overexpression
      of beta2-chimaerin induced important cytoskeletal rearrangements in response to
      matrix stimuli. Transfectant cells also showed activation of MMP-9 activity after
      stimulation with collagen IV and epidermal growth factor. The restitution of
      normal Rac levels by beta2-chimaerin activity induced an increase in the
      sensitivity of tumour cells to extracellular factors, suggesting a regression of
      the malignant phenotype.

PMID- 15583834
TI  - A novel regucalcin gene promoter region-related protein: comparison of nucleotide
      and amino acid sequences in vertebrate species.
AB  - The molecular cloning and sequencing of the cDNA coding for a novel regucalcin
      gene promoter region-related protein (RGPR-p117) from bovine, rabbit and chicken
      livers was investigated using rapid amplification of cDNA endo (RACE) method.
      Their nucleotide and amino acid sequences were compared with human, rat and mouse
      sequences published previously. RGPR-p117 of bovine, rabbit and chicken livers
      consisted of 1052, 1045, and 929 amino acid residues with calculated molecular
      mass of 117, 114, and 103 kDa, and estimated pI of 5.64, 5.84, and 5.59,
      respectively. Comparison analysis revealed that the nucleotide sequences of RGPR
      p117 from mammalian species were highly-conserved in their coding region, and the
      homologies were at least 72.9%. The RGPR-p117 proteins in mammalian species
      consisted of 1045-1060 amino acids, and had 63.1-90.2% identity. Meanwhile, the
      nucleotide and amino acid sequences of chicken RGPR-p117 had at least 36.4 and
      43.7% identities, respectively. Phylogenetic analysis showed that RGPR-p117 in
      six vertebrates appears to form a single cluster. Mammalian RGPR-p117 conserved a
      leucine zipper motif. Moreover, the analysis for subcellular localization of RGPR
      p117 from six vertebrates showed the probability of nuclear localization >52.2%;
      the nuclear localization in rat and mouse was 78.3%. This study demonstrates a
      great conservation of RGPR-p117 genes throughout evolution.

PMID- 15583835
TI  - Quantitative and qualitative alterations of intestinal mucins in BioBreeding
      rats.
AB  - In diabetes-prone BioBreeding rats, an enteropathy often precedes the onset of
      auto-immune insulitis. The present study draws attention to quantitative and
      qualitative alterations of intestinal mucins in this animal model of type 1
      diabetes mellitus. Male and female diabetes-resistant (BBc) and diabetes-prone
      (BBdp) BioBreeding rats fed, from one to two weeks after weaning onwards, either
      a plant-based diabetes-promoting diet (NTP) or a hydrolysed casein diabetes
      protective diet (HC), were sacrificed at 11-14 weeks of age. Proteins and total
      mucins, as well as acid and neutral mucins, were measured in a segment of the
      intestinal tract, located 25-30 cm below the pylorus. No significant difference
      between BBc and BBdp rats was found when fed the HC diet. However, the NTP diet
      lowered both total and neutral mucins, whilst failing to affect significantly
      acidic mucins. The effects of the NTP diet were more pronounced in BBdp rats than
      in BBc rats. It is speculated that the quantitative and qualitative changes
      evoked by the NTP diet in BBdp rats may play a role in the alteration of gut
      permeability found under the same experimental conditions.

PMID- 15583836
TI  - The clinical course of interstitial pneumonia alias chronic fatigue syndrome
      under the control of megadose vitamin C infusion system with
      dehydroepiandrosterone-cortisol annex.
AB  - The year 1995 marked the onset of interstitial pneumonia spread in Nagoya, Japan.
      For the last 9 years, we have been accumulating clinical experience with the
      disease control using the combination of prophylactic use of anti-biotics and
      regular practice of megadose vitamin C infusion with either
      dehydroepiandrosterone-annex or dehydroepiandrosterone-cortisol annex. The
      purpose of this study is to assess the usefulness of our new treatment system for
      the control of interstitial pneumonia alias chronic fatigue syndrome. The results
      obtained are given as follows: i) The long-term maintenance of the above
      treatment system was effective not only for decreasing the risk for recurrence of
      active form pneumonia, but also for prevention of malignancy emergence in aged
      patients with interstitial pneumonia. ii) Evidence is presented to indicate that
      interstitial pneumonia was associated with increased risk for depression of which
      the emergence is a candidate subject causally related to the long-term use of
      glucocorticoid. iii) A patient with both interstitial pneumonia and depression
      was found to be less responsive to our treatment system. It is suggested that the
      use of more dehydroepiandrosterone at the sacrifice of cortisol in the infusion
      annex may be a choice for the control of both interstitial pneumonia and
      depression. iv) The description of chronic fatigue syndrome as regards the
      endocrinological, epidemiological and psychiatric characteristics are in good
      agreement with our experience on patients having interstitial pneumonia, evidence
      in support of our proposal that there is no convincing reasoning to separate
      chronic fatigue syndrome from interstitial pneumonia. v) The long-term practice
      of our treatment system for the control of interstitial pneumonia (an autoimmune
      disease) was found to suppress the inflammatory process but not the fibrotic
      process in the long run. vi) A few innovations were made in our treatment system
      to reduce the risk of bleeding or thrombosis--vascular complications of
      pneumonia. vii) The merit of our treatment system is to create a new hormonal
      environment to improve the state of immunodeficiency by use of a non-steroid
      substance--vitamin C which encounters little resistance from the feedback
      mechanism of steroid metabolism in the in vivo system.

PMID- 15583837
TI  - Identification of a novel class of mammalian phosphoinositol-specific
      phospholipase C enzymes.
AB  - Phosphoinositol (PhoIns)-specific phospholipase C enzymes (PLCs) are central to
      the inositol lipid signaling pathways and contribute to intracellular Ca2+
      release and protein kinase C activation. Five distinct classes of PhoIns-specific
      PLCs are known to exist in mammals, which are activated by membrane receptor
      mediated events. Here we have identified a sixth class of PhoIns-specific PLC
      with a novel domain structure, which we have termed PLC-eta. Two putative PLC-eta
      enzymes were identified in humans and in mice. Sequence analysis revealed that
      residues implicated in substrate binding and catalysis from other PhoIns-specific
      PLCs are conserved in the novel enzymes. PLC-eta enzymes are most closely related
      to the PLC-delta class and share a close evolutionary relationship with other PLC
      isozymes. EST analysis and RT-PCR data suggest that PLC-eta enzymes are expressed
      in several cell types and, by analogy with other mammalian PhoIns-specific PLCs,
      are likely to be involved in signal transduction pathways.

PMID- 15583838
TI  - Computationally analyzing the possible biological function of YJL103C--an ORF
      potentially involved in the regulation of energy process in yeast.
AB  - Although the complete genomes of a number of organisms have been sequenced, the
      biological functions of many genes are still not known. Because experimentally
      studying the functions of those genes one by one requires tremendous time, it is
      vital to use published resources like microarray gene expression data for
      computational analysis of gene functions. One example is YJL103C, a yeast gene of
      unknown function in the Saccharomyces Genome Database (SGD). It is possible to
      quickly infer its biological function by computational analysis. In this study,
      we present an efficient model to explore the biological function of a novel gene
      using microarray data. We showed that the expression pattern of YJL103C is most
      similar to the genes in the energy group and respiratory chain subgroup. We
      further found that YJL103C contains a HAP2,3,4 box in its promoter region and a
      cytochrome C heme-binding signature in its protein sequence. Our findings define
      a potential role for YJL103C in the regulation of energy metabolism, specifically
      in the process of oxidative phosphorylation. Similar bioinformatics methods can
      be applied to infer the biological functions of other novel genes in organisms
      for which microarray data are available. In this work, we selected a single gene
      of unknown function as a case study. By focusing on the power of computer
      analysis and bioinformatics on the available microarray data, we have determined
      the likely biological function of YJL103C. Our study provides a method by which
      to explore the potential function of other genes currently annotated as having an
      unknown function in any organism for which global gene expression data are
      available.

PMID- 15583839
TI  - Occult and obscure bleeding, iron deficiency anemia and other gastrointestinal
      stories (Review).
AB  - Bleeding of which the patient is unaware is the most common form of
      gastrointestinal blood loss, while that of unknown origin persisting or recurring
      after no source has been found at initial or primary endoscopy, or evident
      bleeding from an unidentified source represents the least common. Moreover, iron
      deficiency anemia, a common problem in clinical practice, most frequently
      originates from the gastrointestinal tract. The diagnostic approach to these
      apparently different clinical scenarios is actually very similar. In the present
      review, we summarize the characteristics of the tools employed in the diagnosis
      of these conditions, with a special emphasis on nuclear medicine techniques.

PMID- 15583840
TI  - Tumor associated antigen recognition by autologous serum in patients with breast
      cancer.
AB  - Breast cancer accounts for 30-40% of all deaths from cancers in females. In an
      effort to identify tumor associated antigens that may be useful for
      immunotherapy, we utilized serological analysis of recombinant cDNA expression
      libraries (SEREX) technique to identify breast cancer-associated antigens. SEREX
      screening of cDNA expression libraries derived from 3 breast cancer patients
      identified a total of 88 positive clones (bcg-1 to bcg-88), including 27 hitherto
      unknown sequences. The cDNA sequences and mRNA expression patterns were
      characterized. Seroreactivity of the SEREX clones were determined in sera from 75
      breast cancer patients, 75 colon cancer patients, and 25 healthy donors.
      Expression analysis on a cDNA panel from 17 different normal tissues by reverse
      transcription-PCR (RT-PCR) revealed tissue restricted mRNA expression of 2 of the
      27 unknown antigens. Bcg-72 is expressed only in breast, prostate and thymus,
      while bcg-84 is expressed at moderate levels in testis, spleen and breast. The
      other 25 unknown antigens were expressed in most other tissues. Serologic assay
      revealed that 7 out of the 88 clones showed reactivity to at least one serum from
      either 75 breast or 75 colon cancer patients. These clones did not react with
      sera from a panel of 25 healthy adult individuals. Our results demonstrate the
      utility of the SEREX approach for the identification of potential tumor
      associated antigens in human breast cancer.

PMID- 15583841
TI  - VEGF-subtype specific protection of SCC and HUVECs from radiation induced cell
      death.
AB  - The contribution of VEGF (vascular endothelial growth factor) to angiogenesis and
      tumor aggressiveness has been shown in several tumor types, but no comparative
      data regarding the impact of the VEGF-subtypes on endothelial and tumor cell
      protection are available. Therefore, we analysed the cytoprotective effects of
      the two major soluble VEGF-subtypes, VEGF-121 and -165, on HUVEC cell cultures
      (human umbilical vein endothelial cells) and squamous cell carcinoma (SCC) cell
      lines after ionizing radiation. We performed clonogenic analyses and
      proliferation assays for evaluation of cell survival and proliferative activity.
      Experiments were performed employing different intensities up to 8 Gy with or
      without added recombinant VEGF-121 or -165 and compared to non-irradiated
      cultures. To evaluate a possible contribution of the VEGF-receptors, we performed
      immunohistochemical stainings of VEGF-R1 (flt), -R2 (KDR,flk), and Neuropilin-1.
      In the SCC cell lines and HUVEC cultures, cell survival and proliferative
      activity were reduced in a dosage-dependent manner. The addition of VEGF-121
      yielded a significant increase of resistance from 1.2 to 2.7 Gy (+125%) for
      killing 50% of subjected cells, while VEGF-165 was less effective in this regard
      (+83%). Conversely, in HUVEC cultures, 50%-survival was increased more strongly
      by VEGF-165 compared to VEGF-121 (+100% vs. +43%). Accordingly, proliferation was
      more intensely stimulated in HUVECs by VEGF-165 than by VEGF-121. VEGF-receptors
      were expressed in all cell cultures analysed at comparable levels. We conclude
      that the two VEGF-subtypes differentially increase the survival of tumor and
      endothelial cells after irradiation in vitro. We hypothesise, that the release of
      VEGF by the tumor protects tumor cells and endothelium resulting in increased
      radiation resistance.

PMID- 15583842
TI  - Involvement of intercellular adhesion molecule-1 and beta1 integrin in the
      internalization process to human endothelial cells of group B Streptococcus
      clinical isolates.
AB  - The mechanism by which group B Streptococcus (GBS) interacts with human cells and
      disrupts physiological processes is an intriguing area of investigation and
      continues to unfold. The aim of this study was to investigate the adherence and
      intracellular viability within endothelial ECV304 cells of GBS serotypes Ia, III
      and V isolates from patients and asymptomatic carriers. The GBS isolates from
      patients (GBS-Ia 90222-urine, GBS-III 90356-liquor and GBS-V 90186-blood strains)
      exhibited a more efficient adherence and survival mechanisms to endothelial cells
      than those from asymptomatic carriers (GBS-Ia 85147-oropharynx, GBS-III 80340 and
      GBS-V 88641-vagina strains), independent of bacterial serotypes. Treatment of
      endothelial ECV304 cells with EDTA demonstrated that Ca2+-dependent molecules
      modulated the adherence and internalization process of GBS-Ia and III to ECV304
      cells. SDS-PAGE analysis of samples of biotinylated ECV304 extracts treated with
      GBS clinical isolates (urine 90222-Ia, liquor 90356-III and blood 90186-V
      strains) revealed fragments ranging from approximately 61 to approximately 179
      kDa. Results of immunoassays with ECV304 membrane proteins showed that ICAM-1
      molecules interacted only with GBS-III liquor 90356 strain while beta1 integrin
      interacted with GBS-III liquor 90356 and GBS-V blood 90186 invasive strains.
      Thus, the interaction between ICAM-1 and beta1-integrin seems an additional means
      by which GBS exploits host endothelial cells during infection. These findings add
      to the current understanding of the roles played by multiple receptor-ligand
      systems in the uptake and pathogenesis of GBS infection.

PMID- 15583843
TI  - Multifocal oscillatory potentials in CSNB1 and CSNB2 type congenital stationary
      night blindness.
AB  - We evaluated the function of the inner retina in patients with congenital
      stationary night blindness of the complete (CSNB1) and the incomplete type
      (CSNB2) by recording multifocal oscillatory potentials (mf-OPs). The VERIS system
      was used to record mf-OPs from 61 areas of the central retina from 5 CSNB1
      patients (4 with NYX gene mutation), 6 CSNB2 patients (2 with CACNA1F mutation)
      and 11 control subjects. For each subject group, the first- and second-order
      kernel responses for one eye were analysed and the amplitudes and implicit times
      of their major components compared to 5 concentric rings centred on the fovea. In
      CSNB1 patients, the mf-OP peak amplitudes of the first-order kernel responses
      showed a significant reduction of the first peak without significant reduction of
      the second, whereas in CSNB2 both peak amplitudes were barely discernable from
      noise for all eccentricities. In the second-order kernel, the third peak was
      reduced in CSNB1 patients, and again not discernable from noise in CSNB2
      patients. The difference in amplitude between the control and CSNB1 groups was
      significant for the late components of the first- and the second-order kernel.
      Implicit times were not significantly altered. The difference in mf-OP amplitude
      between CSNB1 and CSNB2 patients reflects the different molecular mechanisms
      underlying the two types of disease, which differentially affect the
      postreceptoral pathways of cone signal processing. The well-preserved peak 2
      amplitudes of first-order mf-OPs and peak 3 amplitudes of second-order mf-OPs in
      CSNB1 patients point to a major impact of OFF-pathway components on these
      responses which are not present in CSNB2 patients. In conclusion, our results
      show that CSNB1 and CSNB2 are two different types of disease, not only on a
      genetic but also on a pathophysiological level.

PMID- 15583844
TI  - The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates
      expression levels of Bcr-abl, c-Myc and HDAC3 in chronic myeloid leukemia cell
      lines.
AB  - In chronic myelocytic leukemia (CML) the activity of the Bcr-Abl tyrosine kinase
      is known to activate a number of molecular mechanisms, which inhibit apoptosis.
      In the present study, we show that the histone deacetylase inhibitor SAHA
      (suberoylanilide hydroxamic acid) markedly decreases protein expression levels of
      Bcr-Abl and c-Myc in BV-173 cells, while in K562 cells only a minor decrease of
      Bcr-Abl protein levels is observed while a considerable reduction of c-Myc
      protein expression may only be achieved at higher concentrations of SAHA. In
      addition, we found BV-173 cells to be more sensitive to SAHA-induced apoptosis
      when compared to K562 cells. Even though earlier reports on SAHA considerably
      focused on its inhibitory effect on HDAC enzymatic activity, we report herein a
      significant down-regulation of HDAC3 protein expression levels following
      treatment with SAHA in BV-173 cells, but not in K562 cells. In conclusion, our
      results imply a molecular mechanism for SAHA-induced apoptosis in BV-173 cells,
      which involves decreased protein expression levels of Bcr-Abl, c-Myc and HDAC3.

PMID- 15583845
TI  - Adiponectin gene variation associates with the increasing risk of type 2 diabetes
      in non-diabetic Japanese subjects.
AB  - Adiponectin is an adipocyte-secreted protein that is known to modulate insulin
      sensitivity and glucose homeostasis. A number of genetic variations have been
      studied. Among them, two single-nucleotide polymorphisms (SNP45T>G, SNP276G>T)
      showed an association with type 2 diabetes in the Japanese population. In this
      study, we examined the association between these SNPs and risk factors of type 2
      diabetes in 194 non-diabetic Japanese subjects. SNP45 was associated with insulin
      sensitivity (determined by HOMA-IR, p=0.046) and obesity (body mass index; BMI,
      p=0.043). SNP276 showed a stronger association with HOMA-IR (p=0.018) and BMI
      (p=0.017). However, neither SNP had an association with insulin secretion
      (insulinogenic index) and plasma lipid levels. Moreover, a linkage dis
      equilibrium was observed between SNP45 and SNP276. Carriers with SNP45G-SNP276G
      haplotype had higher BMI (p=0.034) and carriers with SNP45T-SNP276T haplotype had
      lower BMI (p=0.005) and HOMA-IR (p=0.037). Adiponectin gene variations showed an
      association with obesity and insulin sensitivity, and adiponectin genotypes may
      predict the increasing risk for type 2 diabetes in non-diabetic subjects.

PMID- 15583846
TI  - Nasal middle vault support: a new technique.
AB  - A novel technique for maintaining internal nasal valve anatomic and physiologic
      integrity at the time of hump reduction is proposed. The procedure involves
      mobilizing the anterior edge of the upper lateral cartilage after submucosal
      dissection. Reduction of the anterior border of the septal cartilage and
      reconstruction of the middle vault of the nose is accomplished by placing the
      upper lateral cartilage medial border on the reduced edge of the septum using a
      vest-over technique. The technique was successfully used for 32 nonconsecutive
      patients over a 4-year period.

PMID- 15583847
TI  - Simple technique for inverted nipple correction.
AB  - Several different techniques have been developed and currently are in use for
      correction of the inverted nipple. The diversity of techniques indicates the lack
      of a good, sustainable, and durable solution for this quite common problem. This
      report discusses a new technique in which two flaps are inserted beneath the
      nipple through a small tunnel. The advantages of this procedure are its
      simplicity, the creation of a durable support for the nipple, and the lack of
      transverse scars in the areola surrounding the nipple. The follow-up period up to
      4 years for 11 patients (18 nipples) demonstrates the validity of this technique.

PMID- 15583848
TI  - A case report of prefilled polysaccharide hydrogel breast implant rupture:
      clinical, MRI, and pathologic findings.
AB  - A case of a ruptured prefilled polysaccharide hydrogel breast implant with its
      radiologic and pathologic findings is presented. Usually, hydrogel spreads out in
      tissues with swelling and edema after rupture of an implant. However, in this
      case, a small amount of hydrogel leakage was misdiagnosed with ultrasonography as
      a benign breast mass. Therefore, it is advisable to evaluate a breast mass after
      augmentation with a hydrogel breast implant using magnetic resonance imaging to
      differentiate it from the hydrogel itself.

PMID- 15583849
TI  - Carbon dioxide laser therapy for an inflammatory linear verrucous epidermal
      nevus: a case report.
AB  - The treatment of an inflammatory linear verrucous epidermal nevus (ILVEN), an
      uncommon type of epidermal nevus, is still controversial. The use of laser
      therapy is a recently reported method. Although various results have been
      reported with the use of the laser in the treatment epidermal nevis, the authors
      have not seen any report on the use of the carbon dioxide laser in ILVEN
      treatment. They present case of ILVEN treated with the carbon dioxide laser. All
      symptoms (erythema, excoriation, granulation, and pruritus) disappeared. Instead,
      a pale pigmentation was seen.

PMID- 15583850
TI  - DNA microarray for rapid detection of mitochondrial DNA haplotypes of chum
      salmon.
AB  - For use in genetic stock identification, we developed an oligonucleotide (DNA)
      microarray hybridization method for rapid and accurate detection of nucleotide
      sequence variations in 20 previously identified variable nucleotide sites in
      about 500 bp within the 5' half of the control region of mitochondrial DNA of
      chum salmon (Oncorhynchus keta). The method includes immobilization of
      synthesized oligonucleotides containing respective polymorphic sites on a glass
      slide precoated with polycarbodiimide resin, a 2-hour hybridization with DNA
      microarray of biotinylated polymerase chain reaction fragments spanning the 5'
      variable portion followed by short washing, and visualization of hybridization
      signals by conventional ABC method and scanner-assisted computation of signal
      intensity on a computer. The entire process of hybridization and detection was
      completed within 4 hours. The resulting DNA microarray could detect all of the
      single nucleotide mutations and therefore could be used to identity the sequence
      variations defining 30 mtDNA haplotypes of chum salmon as revealed previously by
      nucleotide sequence analysis.

PMID- 15583851
TI  - Oncogenic tyrosine kinases.

PMID- 15583852
TI  - Abl: the prototype of oncogenic fusion proteins.
AB  - Since it was first recognized, chronic myeloid leukemia (CML) has always
      represented a unique model to understand the molecular mechanisms underlying the
      onset and progression of a leukemic process. CML was the first recognized form of
      cancer to have a strong association with a recurrent chromosomal abnormality, the
      t(9;22) translocation, which generates the so-called Philadelphia (Ph)
      chromosome. Twenty years later, this abnormality was shown to cover a specific
      molecular defect, a hybrid BCR-ABL gene, strongly implicated in the pathogenesis
      of the disease through the production of a protein with a constitutive tyrosine
      kinase activity. Although we still lack a complete definition of all the
      transformation pathways activated by Bcr-Abl, the recent introduction into
      clinical practice of tyrosine kinase inhibitor represents a major breakthrough to
      the management of CML and, furthermore, promises to usher in molecularly targeted
      therapy for other types of leukemia, lymphoma and cancer.

PMID- 15583853
TI  - Oncogenic derivatives of platelet-derived growth factor receptors.
AB  - Platelet-derived growth factor receptors (PDGFRs) and their ligands, platelet
      derived growth factors (PDGFs) play critical roles in mesenchymal cell migration
      and proliferation. In embryogenesis the PDGFR/PDGF system is essential for the
      correct development of the kidney, cardiovascular system, brain, lung and
      connective tissue. In adults, PDGFR/PDGF is important in wound healing,
      inflammation and angiogenesis. Abnormalities of PDGFR/PDGF are thought to
      contribute to a number of human diseases, and especially malignancy. Constitutive
      activation of the PDGFRalpha or PDGFRbeta receptor tyrosine kinases is seen in
      myeloid malignancies as a consequence of fusion to diverse partner genes, and
      activating mutations of PDGFRalpha are seen in gastrointestinal tumours (GISTs).
      Autocrine signalling as a consequence of PDGF-B overexpression is clearly
      implicated in the pathogenesis of dermatofibrosarcoma protruberans (DFSP) and
      overexpression of PDGFRs and/or their ligands has been described in many solid
      tumours. PDGFR signalling is inhibited by imatinib mesylate, and this compound
      has clear clinical activity in patients with myeloid malignancies, GIST and DFSP.

PMID- 15583854
TI  - Kit as a human oncogenic tyrosine kinase.
AB  - Signals through Kit receptor tyrosine kinase are essential for development of
      erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal
      (ICCs). Mice and rats with a double gene dose of loss-of-function mutations of
      Kit show depletion of these cells. Although human homozygotes with loss-of
      function mutations of Kit have not been reported, gain-of-function mutations of
      Kit result in development of tumors from mast cells, germ cells and ICCs in
      humans. The ICC tumors are called gastrointestinal stromal tumors (GISTs), and
      GISTs are a good target for the Kit inhibitor imatinib mesylate. The
      interrelationship between the type of Kit gain-of-function mutations and the
      therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit
      is interesting from both a biological and clinical view-point.

PMID- 15583855
TI  - Normal and oncogenic FLT3.
AB  - FLT3, a member of the class III receptor tyrosine kinases (RTKs), is
      preferentially expressed on the cell surface of hematopoietic progenitors, and
      the ligand of FLT3 (FL) is expressed as a membrane-bound or soluble form by bone
      marrow stroma cells. It has been disclosed that FL-FLT3 interaction plays an
      important role in the maintenance, proliferation and differentiation of
      hematopoiesis. FLT3 is also expressed in a high proportion of acute myeloid
      leukemia (AML) and B-lineage acute lymphoblastic leukemia cells. Activating
      mutations of FLT3 are the most frequent genetic lesions in AML, and AML patients
      with FLT3 mutations have a worse prognosis than those with normal FLT3. Exploring
      the mechanism by which FLT3 mutations cause autoactivation and uncontrolled
      signaling might lead to a better understanding of how FLT3 becomes oncogenic and
      provide insights for the development of new drugs.

PMID- 15583856
TI  - The emerging normal and disease-related roles of anaplastic lymphoma kinase.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, the normal role
      of which remains to be completely elucidated. Although work carried out in
      mammals suggests a function in neural development, results from studies in
      Drosophila indicate an additional role in visceral muscle differentiation. The
      aberrant expression of full-length ALK receptor proteins has been reported in
      neuroblastomas and glioblastomas, while the occurrence of ALK fusion proteins in
      anaplastic large cell lymphoma (ALCL) has resulted in the identification of the
      new tumor entity, ALK-positive ALCL. ALK represents one of few examples of a
      receptor tyrosine kinase implicated in oncogenesis in both haematopoietic and non
      haematopoietic tumors, given that ALK fusions also occur in the mesenchymal tumor
      known as inflammatory myofibroblastic tumor (IMT). The study of ALK fusion
      proteins, besides demonstrating their importance in tumor development, has also
      raised the possibility of new therapeutic treatments for patients with ALK
      positive malignancies.

PMID- 15583857
TI  - Dysfunction of the RET receptor in human cancer.
AB  - RET is the receptor for glial-derived neurotrophic factor growth factors. It is a
      paradigm of a single gene that causes different types of human cancer when
      targeted by different genetic alterations. Like other receptor tyrosine kinases,
      once activated, RET recruits a variety of signaling molecules that mediate
      biological responses. Here we review data on the signaling pathways that lead to
      RET-mediated cell transformation and recent evidence that manipulation of RET
      holds promise for thyroid cancer treatment.

PMID- 15583858
TI  - Role of HER2/neu in tumor progression and therapy.
AB  - HER2 (human epidermal growth factor receptor-2; also known as erbB2) and its
      relatives HER1 (epidermal growth factor receptor; EGFR), HER3 and HER4 belong to
      the HER family of receptor tyrosine kinases. In normal cells, activation of this
      receptor tyrosine kinase family triggers a rich network of signaling pathways
      that control normal cell growth, differentiation, motility and adhesion in
      several cell lineages. The first tumor studied for an alteration of the HER2
      oncogene is breast carcinoma, and so far the majority of studies have been
      performed on this oncotype. Although involvement of HER2 as a cause of human cell
      transformation needs to be further investigated, overexpression of the HER2
      oncogene in human breast carcinomas has been associated with a more aggressive
      course of disease. It has been suggested that this association depends on HER2
      driven proliferation, vessel formation and/or invasiveness; however, poor
      prognosis may not be directly related to the presence of the oncoprotein on the
      cell membrane but instead to the breast carcinoma subset identified by HER2
      overexpression and characterized by a peculiar gene expression profile, as
      recently identified. HER2-positive tumors were recently shown to benefit from
      anthracyclin treatment and to be resistant to endocrine therapy. Despite the fact
      that many pathways interacting with HER2 are still not fully understood, this
      tyrosine kinase receptor is, to date, a promising molecule for targeted therapy.

PMID- 15583859
TI  - Degradation of proinsulin C-peptide in kidney and placenta extracts by a specific
      endoprotease activity.
AB  - Degradation of proinsulin C-peptide in mouse kidney and human placenta extracts
      was studied using reverse-phase high-performance liquid chromatography and nano
      electrospray mass spectrometry. In total, 15 proteolytic cleavage sites were
      identified in human and mouse C-peptides. Early sites included the peptide bonds
      N-terminal of Val/Leu10, Leu12, Leu21, Leu24 and Leu26 in different combinations
      for the two tissues and two peptides. Notably, these cleavages were N-terminal of
      a hydrophobic residue, and all but one N-terminal of Leu. A late degradation
      product of the human peptide detected in the kidney extract was the C-terminal
      hexapeptide, containing just one residue more than the biologically active C
      terminal pentapeptide of C-peptide. We conclude that the degradation of C-peptide
      in kidney and placenta follows similar patterns, dominated by endopeptidase
      cleavages N-terminal of Leu.

PMID- 15583860
TI  - Localization of integrated adenovirus DNA in the hamster genome.
AB  - Adenovirus DNA integrated into the genomes of adenovirus-transformed hamster
      cells or of adenovirus type 12 (Ad12)-induced hamster tumor cells can be located
      at many different chromosomal sites. This raises the question as to whether
      distinct isochores of the hamster cell genome might be more accessible to
      recombination with adenovirus DNA. In Ad12- or Ad2-transformed hamster cell
      lines, and in Ad12 revertants, the investigated integrated viral DNA sequences
      were assigned to isochore families by analyzing DNA fractions from preparative
      CsCl density gradients for their buoyant densities (and, therefore, GC levels)
      and for the presence of viral DNA. Adenovirus DNA sequences were found in
      different isochores, which did not generally match the base composition of viral
      sequences. This is in apparent contrast to what was previously observed with
      retroviral integration. However, in cell lines carried in culture for many years,
      the viral DNA sequences might have been transposed to different isochore
      positions, since the host sequences flanking the viral DNA appear to have been
      conserved.

PMID- 15583861
TI  - Morphine but not fentanyl and methadone affects mitochondrial membrane potential
      by inducing nitric oxide release in glioma cells.
AB  - We have observed that treatment of human glioma cells with morphine in the
      nanomolar range of concentration affects the mitochondrial membrane potential.
      The effect is specific to morphine and is mediated by naloxone-sensitive
      receptors, and is thus better observed on glioma cells treated with desipramine;
      moreover, the mitochondrial impairment is not inducible by fentanyl or methadone
      treatment and is prevented by the nitric oxide (NO) synthase inhibitor L-NAME. We
      conclude that in cultured glioma cells, the morphine-induced NO release decreases
      the mitochondrial membrane potential, as one might expect based on the rapid
      inhibition of the respiratory chain by NO. The identification of new intra
      cellular pathways involved in the mechanism of action of morphine opens
      additional hypotheses, providing a novel rationale relevant to the therapy and
      toxicology of opioids.

PMID- 15583863
TI  - Issues surrounding sleep-dependent memory consolidation and plasticity.
AB  - There is a growing body of evidence in support of sleep-dependent memory
      consolidation and plasticity. However, there are also examples of memory
      development and plasticity in the absence of sleep, casting doubt on an exclusive
      sleep-dependent memory hypothesis. As a result, polarized stances have arisen
      within the field. Here we reflect on these findings, and explore how they maybe
      reconcilable in a unified approach to understanding the roles of wake, sleep and
      specific sleep stages in successful memory processing and brain plasticity.

PMID- 15583862
TI  - Modulation of signal transduction through the cellular prion protein is linked to
      its incorporation in lipid rafts.
AB  - Because expressed at a significant level at the membrane of human T cells, we
      made the hypothesis that the cellular prion protein (PrPc) could behave as a
      receptor, and be responsible for signal transduction. PrPc engagement by specific
      antibodies was observed to induce an increase in cytosolic calcium concentration
      and led to enhanced activity of Src protein tyrosine kinases. Antibodies to CD4
      and CD59 did not influence calcium fluxes or signaling. The effect was maximal
      after the formation of a network involving avidin and biotinylated antibody to
      PrPc and was inhibited after raft disruption. PrPc localization was not
      restricted to rafts in resting cells but engagement was a prerequisite for
      signaling induction, with concomitant PrPc recruitment into rafts. These results
      suggest a role for PrPc in signaling pathways, and show that lateral
      redistribution of the protein into rafts is important for subsequent signal
      transduction.

PMID- 15583864
TI  - The muscle ultrastructure: a structural perspective of the sarcomere.
AB  - Muscle ultrastructure is characterised by a complex arrangement of many protein
      protein interactions. The sarcomere is the basic repeating unit of muscle, formed
      by two transverse filament systems: the thick and thin filaments. While actin and
      myosin are the main contractile elements of the sarcomere, other proteins act as
      scaffolds, control ultrastructure composition, regulate muscle contraction, and
      transmit tension between sarcomeres and hence to the whole myofibril. Elucidation
      of the structures of muscle proteins by X-ray crystallography and nuclear
      magnetic resonance spectroscopy has been essential in understanding muscle
      contraction, enabling us to relate biological to structural information. These
      structures reveal how components of the muscle interact, how different factors
      influence conformational changes within these proteins, and how mutant muscle
      proteins may interfere with the regulatory fine-tuning of the contractile
      machinery, hence leading to disease in some cases. Here, structures solved within
      the sarcomere have been reviewed in order to put the numerous components into
      context.

PMID- 15583865
TI  - Directed evolution of enzymes for biocatalysis and the life sciences.
AB  - Engineering the specificity and properties of enzymes and proteins within rapid
      time frames has become feasible with the advent of directed evolution. In the
      absence of detailed structural and mechanistic information, new functions can be
      engineered by introducing and recombining mutations, followed by subsequent
      testing of each variant for the desired new function. A range of methods are
      available for mutagenesis, and these can be used to introduce mutations at single
      sites, targeted regions within a gene or randomly throughout the entire gene. In
      addition, a number of different methods are available to allow recombination of
      point mutations or blocks of sequence space with little or no homology.
      Currently, enzyme engineers are still learning which combinations of selection
      methods and techniques for mutagenesis and DNA recombination are most efficient.
      Moreover, deciding where to introduce mutations or where to allow recombination
      is actively being investigated by combining experimental and computational
      methods. These techniques are already being successfully used for the creation of
      novel proteins for biocatalysis and the life sciences.

PMID- 15583866
TI  - The role of the trans-Golgi network in varicella zoster virus biology.
AB  - The task of assembling nascent virions presents a formidable challenge to large,
      enveloped DNA viruses such as varicella zoster virus (VZV). After parasitising
      the host cell's compartmentalised biosynthetic machinery, viral constituents must
      be brought together in appropriate proportions for packaging and export. Recent
      evidence places the trans-Golgi network (TGN) in an orchestrating role with
      respect to the assembly, envelopment and egress of herpesviruses. This role
      accords with known functions of the TGN in the uninfected cell. The targeting of
      viral glycoproteins to the TGN appears to provide a crucial platform for viral
      assembly. Tegument proteins, interacting with the cytoplasmic domains of
      glycoproteins, in turn recruit nucleocapsids to the developing supramolecular
      array. Molecular studies are continually refining understanding of these
      processes, building upon elegant electron microscopic data. Knowledge of VZV's
      use of endogenous trafficking pathways from the TGN sheds light on important
      aspects of viral behaviour in vitro and in vivo.

PMID- 15583867
TI  - Neurofilament proteins in neurodegenerative diseases.
AB  - The function of neurofilaments, the major component in large myelinated neurons,
      is not well understood even though they were discovered as structures over 100
      years ago. Recent studies have suggested that neuro-filaments are closely related
      to many neurodegenerative diseases, such as amyotrophic lateral sclerosis,
      Parkinson disease Alzheimer disease, and diabetes. Using in vitro assays,
      cultures and transgenic mice, these studies provided new insights into
      neurofilament function. The function of each subunit, the relationship of
      neurofilaments with other cytoskeletal elements and their clinical significance
      are topics of increasing attention.

PMID- 15583868
TI  - Pharmacological attenuation of apoptosis in reoxygenated endothelial cells.
AB  - BRX-235 (Iroxanadine), a novel drug developed by Biorex (Hungary), was previously
      characterized as a vasculoprotector against atherosclerosis, an activator of p38
      kinase, and an enhancer of stress-responsive heat shock protein (Hsp) expression.
      The present data demonstrate that BRX-235 may improve survival of vascular
      endothelial cells (ECs) following ischemia/reperfusion stress. ECs cultured from
      human umbilical veins were exposed to hypoxia/reoxygenation to mimic
      ischemia/reperfusion. Caspase activation and apoptosis were monitored in the
      reoxygenated cells. Addition of BRX-235 (0.1-1 microM) to culture medium prior to
      hypoxia or at start of reoxygenation significantly reduced the caspase-dependent
      apoptosis. The cytoprotection conferred by the pre-hypoxic drug administration
      was sensitive to quercetin and seems to be based on enhanced Hsp accumulation in
      stressed ECs. In the case of post-hypoxic drug administration, the cytoprotection
      was strongly inhibited by SB202190 and SB203580 and appears to be associated with
      enhanced p38 kinase activation in reoxygenated ECs.

PMID- 15583870
TI  - Acute effects of adrenergic agents on post-defibrillation arrest time in a
      cultured heart model.
AB  - Possible drug interactions with electrical defibrillation were examined. We
      tested the hypothesis that adrenergic agents (epinephrine, norepinephrine,
      isoproterenol) and a calcium channel blocker (verapamil), when applied acutely,
      alter the duration of arrest following a defibrillator shock. A secondary
      hypothesis (based on observations) was that the drugs alter the occurrence of
      changes to normal rhythms following the shock. Dissociated heart cells from 10
      day chicken embryos were cultured to form spherical aggregates and plated in
      petri dishes. In the experiments, the spheres were paced at 0.75 V/cm above
      contraction threshold, and a biphasic defibrillator shock was applied for 1 ms at
      46 V/cm. The arrest time and occurrence of rhythm changes were recorded. The
      adrenergic agents shortened the duration of arrest following a defibrillator
      shock, while the calcium channel blocker lengthened the arrest time. Comparisons
      with the control proportion of double beats showed no significant change with the
      adrenergic agents and a decrease with verapamil.

PMID- 15583869
TI  - TRAF4 functions as an intermediate of GITR-induced NF-kappaB activation.
AB  - Members of the tumor necrosis factor receptor (TNFR) family regulate the
      activation, differentiation, and function of many cell types, including cells of
      the immune system. TNFR-associated factors (TRAFs) function as adapter molecules
      controlling signaling pathways triggered by TNFR family members, such as
      activation of nuclear factor kappaB (NF-kappaB). Despite intensive research, the
      function of TRAF4 in signaling pathways triggered by TNFR-related proteins
      remains enigmatic. Intriguingly, our functional studies indicated that TRAF4
      augments NF-kappaB activation triggered by glucocorticoid-induced TNFR (GITR), a
      receptor expressed on T cells, B cells, and macrophages. Further analyses
      revealed that TRAF4-mediated NF-kappaB activation downstream of GITR depends on a
      previously mapped TRAF-binding site in the cytoplasmic domain of the receptor and
      is inhibited by the cytoplasmic protein A20. GITR is thought to inhibit the
      suppressive function of regulatory T cells (Treg cells) and to promote activation
      of T cells. Taken together, our studies provide the first indications that TRAF4
      elaborates GITR signaling and suggest that TRAF4 can modulate the suppressive
      functions of Treg cells.

PMID- 15583871
TI  - Mitochondrial permeability transition triggers the release of mtDNA fragments.
AB  - Fragments of mitochondrial DNA are released from mitochondria upon opening of the
      mitochondrial permeability transition pore. Cyclosporin A, an inhibitor of pore
      opening, completely prevented the release of mitochondrial fragments. Induction
      of mitochondrial permeability transition and subsequent release of the fragments
      of mitochondrial DNA could be one cause of genomic instability in the cell.

PMID- 15583872
TI  - Functional and biochemical characteristics of mitochondrial fractions from rat
      liver in cold-induced oxidative stress.
AB  - We determined characteristics of rat liver mitochondrial fractions, resolved at
      1000 (M1), 3000 (M3), and 10,000 g (M10) after 2 and 10 days cold exposure. In
      all groups, the M1 fraction exhibited the highest oxidative capacity, oxidative
      damage, H2O2 production rate, and susceptibility to stress conditions, and the
      lowest antioxidant levels. Cold exposure increased cytochrome oxidase activity in
      all fractions and succinate-supported O2 consumption in the M1 and M10 fractions
      during state 3 and state 4 respiration, respectively. With succinate, the H2O2
      release rate increased in all fractions during state 4 and state 3 respiration,
      whereas with pyruvate/malate, it increased only during state 4 respiration.
      Increases in tissue mitochondrial proteins caused a faster H2O2 flow from the
      mitochondrial to cytosolic compartment, which was limited by the reduction in the
      M1 fraction. Despite increased liposoluble antioxidant levels, cold also caused
      enhanced oxidative damage and susceptibility to oxidative challenge and Ca2+
      induced swelling in all fractions. These changes leading to elimination of H2O2
      overproducing mitochondria avoided excessive tissue damage. We propose that
      triiodothyronine, whose levels increase in the cold environment, brings about the
      biochemical changes producing oxidative damage and those limiting its extent.

PMID- 15583873
TI  - [Bioequivalence of L-thyroxine tablets and a liquid L-thyroxine solution in the
      treatment of hypothyroid patients].
AB  - BACKGROUND AND PURPOSE: The therapeutic equivalence of L-thyroxine (T(4)) tablets
      and a new liquid T(4) solution was investigated in patients with hypothyroidism.
      PATIENTS AND METHODS: The study was unblinded, multicentric and prospective: 136
      patients (with autoimmune thyroiditis, after thyroid surgery and/or after therapy
      with radioiodine), who had been treated with T(4) tablets, were switched to a
      treatment with a liquid T(4) solution (containing 5 microg T(4) per drop) in the
      same dosage. Thyrotropin (TSH) was measured after 1, 2, 3, and 6 months; the dose
      of the T4 solution was adapted to obtain a midnormal TSH level. RESULTS: The T(4)
      dose remained constant during the 6 months. Dose adaptations were necessary in 19
      23% of patients at the different timepoints, with dose reductions and increases,
      respectively, becoming equally frequently necessary. The mean TSH level was 0.79
      mU/l at the beginning and 0.81 mU/l after 6 months; similarly, the mean levels of
      free triiodothyronine (fT(3)) and free thyroxine (fT(4)) were equivalent. The
      liquid T(4) solution was well tolerated: adverse events were noted in three
      patients (1.8%); one serious adverse event (thyroid carcinoma) showed no
      correlation to the treatment. CONCLUSION: T(4) tablets and liquid T(4) solution
      have been proven to be therapeutically equivalent; the use of liquid T(4)
      solutions will have advantages in the treatment of hypothyroid infants or elderly
      patients with disturbed swallowing, patients who need a differentiated titration
      of the T(4) dose, as well as patients with an allergy against inactive
      ingredients of L-thyroxine tablets.

PMID- 15583874
TI  - [Noninvasive detection of coronary stenosis using 16-slice detector computed
      tomography in carefully selected patients].
AB  - BACKGROUND AND PURPOSE: Due to technical improvements, multislice spiral computed
      tomography (MSCT) has become available for the noninvasive visualization of human
      coronary arteries. The current scanner generation provides 16 detector slices.
      The aim of the present study was to evaluate the influence of a careful patient
      selection on the diagnostic accuracy of noninvasive angiography. PATIENTS AND
      METHODS: Out of a study population of 60 patients, 36 with mild coronary
      calcifications (Agatston score < 500) were selected for the present retrospective
      analysis. In addition to conventional coronary angiography (CCA), all patients
      underwent a noninvasive MSCT examination of the coronary arteries. All coronary
      segments were assessed with respect to image quality and presence of severe
      lesions with a diameter stenosis >or = 50%. The MSCT examinations were performed
      using a Sensation 16 scanner (Siemens Medical Systems, Forchheim, Germany).
      RESULTS: The Agatston score of the study population was 83.3 +/- 125.4 (0-491.3),
      calcium mass 14.7 +/- 21.4 (0-83) mg CaHA (calcium hydroxyapatite). Diagnostic
      image quality could be obtained in 391/455 coronary segments (86%). 26 lesions >
      or = 50% could be detected by MSCT, CCA confirmed the presence of 21 lesions. No
      false-negative results were obtained (sensitivity: 100%, specificity: 99%,
      positive predictive value: 0.81, negative predictive value: 1.0). CONCLUSION: The
      new MSCT generation with 16 detector slices permits a noninvasive visualization
      of the coronary arteries with good image quality. It could be shown that a
      careful patient selection is of major importance for the diagnostic accuracy of
      MSCT imaging. It appears to be useful to perform a stepwise imaging, starting
      with a native scan to rule out severe calcifications. Prospective multicenter
      trials with larger patient numbers are required to confirm these initial results.

PMID- 15583875
TI  - [Cardiovascular risk assessment for informed decision making. Validity of
      prediction tools].
AB  - BACKGROUND AND PURPOSE: Patient involvement in health care decisions is
      increasingly requested. The authors investigated whether currently available
      assessment tools for prediction of cardiovascular risk can be used for individual
      risk prediction as a basis of informed decision making. METHODS: The authors
      searched for risk assessment tools and respective validation studies in Medline
      (until August 16, 2004) and the Cochrane Library (issue 2/2004). The following
      criteria were used for evaluation of prognostic studies: (1) discrimination
      between risk groups; (2) predictive values; (3) prognostic agreement; (4)
      transferability across populations. RESULTS: A total of twelve assessment tools
      were identified. The Framingham function, Sheffield Tables, Canadian Tables,
      Framingham Categorial, New Zealand, Joint British, and European Charts (1994 and
      1998) are based on the Framingham Study; PROCAM Risk Score, UKPDS Risk Engine,
      and SCORE Risk Charts use different source data. Framingham-based instruments
      overestimate cardiovascular risk of Central-European populations by at least 30%,
      with substantial regional variation even within a country (between 30% and 100%,
      British Regional Heart Study). Therefore, prior to application the assessment
      tools would need recalibration using regional data of cardiovascular mortality
      and adjustment for social class differences. Published sensitivity, specificity,
      and C-statistics for external validation (area under the curve [AUC]
      approximately 0.6) are clearly inferior to internal validation (AUC approximately
      0.8). Agreement between instruments beyond chance is moderate (kappa
      approximately 0.5). No studies on external validation could be identified for the
      new European SCORE Risk Charts and UKPDS Risk Engine. CONCLUSION: Validation of
      currently available assessment tools for cardiovascular risk prediction is
      inadequate. Uncritical use may lead to substantial under- or overestimation of
      individual cardiovascular risk and inappropriate treatment decisions.

PMID- 15583876
TI  - [Osteoporosis -- mode or disease?].

PMID- 15583878
TI  - [Suspected diagnosis and hospital observation of suspected cases].

PMID- 15583877
TI  - [Body weight regulation through the central nervous system. The development of a
      pathogenetically based adiposity therapy].
AB  - The last decade witnessed a dramatic increase in knowledge concerning regulation
      of body weight and obesity. According to recent concepts constancy of body weight
      is a side product of regulatory events which ensure constant glucose fluxes to
      the brain. Within these control systems glucocorticoids and melanocortins play a
      fundamental role at several sites. The melanocortin neurons in the arcuate
      nucleus of the hypothalamus are important mediators of the feedback effects of
      leptin and insulin. Glucocorticoid and mineralocorticoid receptors in hippocampal
      neurons are crucial, as they define the balance between glucose allocation
      processes and food intake. Thereby, the hippocampal structures determine the
      setpoint for body weight regulation. A modulation of these brain structures by
      intranasal administration of melanocortin and inhisulin has been shown to reduce
      body weight and body fat mass in humans. So the manipulation of weight-regulating
      centers in the brain opens a novel approach to a pathogenetically based treatment
      of obesity.

PMID- 15583879
TI  - [Metastatic alveolar soft tissue sarcoma in a 26-year-old patient].

PMID- 15583880
TI  - [Berlin Society of Internal Medicine].

PMID- 15583881
TI  - [Scientific medicine -- only one among others?].

PMID- 15583883
TI  - [Complications of infectious diseases and benefits of immunization].
AB  - Significant progress regarding hygiene, nutrition, and antimicrobial treatment as
      well as immunizations have lead to a significant decline of morbidity and
      mortality of infectious diseases in the recent past. Furthermore, immunizations
      are one of the most cost-effective tools for prevention. However, lack of
      perception of the substantial risks of complications associated with infectious
      diseases cause doubts about the necessity of immunizations today. This
      development is highly worrisome and needs to be adequately addressed by informing
      physicians and the public about the risks of vaccine-preventable diseases,
      efficiency, safety and benefits of available vaccines, as well as providing
      convincing arguments justifying current immunization recommendations. These
      activities are indispensable for successful implementation and continuation of
      current immunization programs.

PMID- 15583884
TI  - [Relevance of sentinel surveillance systems for the implementation and evaluation
      of vaccination strategies].
AB  - In sentinel surveillance a prearranged sample of reporting sources-often
      healthcare providers-agrees to report all cases of defined conditions. The German
      "Protection Against Infection Act" (IfSG) provides a mandate to the Robert Koch
      Institute (RKI) to establish sentinel surveillance of not notifiable diseases
      relevant to public health. Sentinel systems with RKI involvement include two
      networks of private practitioners reporting cases of influenza and measles
      (within the Working Groups on Influenza and Measles, respectively). In addition a
      laboratory-based sentinel system reports cases of certain bacterial infections in
      children. Results from these systems serve as a basis for framing vaccination
      recommendations and goals as well as for the evaluation, adjustment and promotion
      of vaccination strategies. The data indicate time trends (e. g. number of cases
      by season, age and region) and supply specific information (e. g. for
      determination of risk factors, distribution of pathogens). Methodological
      problems of sentinel surveys (e. g. selection of appropriate samples, population
      based estimates) can be accounted for with appropriate methods of analysis. More
      effective implementation of sentinel surveillance in Germany could be achieved
      through better coordination of existing structures. This would make more
      effective use of limited resources and better enable timely and flexible
      investigation of conceptual and organisational questions.

PMID- 15583885
TI  - [Vaccination coverage in Germany].
AB  - Up-to-date information on vaccination coverage and seroprevalence are the basis
      for enhancing the acceptance of vaccination and increasing vaccination coverage.
      In Germany these data are currently only available to a limited extent. Existent
      data sources only permit estimates of vaccination coverage or are not age
      appropriate, such as the representative data from the school entry examinations.
      Despite increasing vaccination coverage of children and adolescents in recent
      years, existent data indicate important coverage gaps for certain vaccines. In
      addition, the vaccination status in adults is often incomplete. Improved
      surveillance of vaccination coverage and seroprevalence could make an important
      contribution to closing gaps in vaccination coverage.

PMID- 15583886
TI  - [Adverse events following immunisation in Germany from 1.1.2001 to 31.12.2003].
AB  - The German Protection Act against Infection (Infektionsschutzgesetz) came into
      effect on 1 January 2001. Physicians must report complications after vaccination
      to local heath authorities according to Article 6 No. 3. . The local heath
      authorities send notifications to the Paul-Ehrlich-Institut (PEI). Between 1
      January 2001 and 31 December 2003, a total of 941 reports from local public
      health authorities were registered in a central database and assessed. Compared
      to the number of reports of suspected adverse drug reactions sent to the PEI
      independently in the same time period by the pharmaceutical companies and the
      German Drug Commissions (Arzneimittelkommissionen) (n=2.338), underreporting has
      to be considered. Age distribution in the reports from local public health
      authorities revealed the following pattern: 33.8% of reports concerned adults (18
      59 years old), 25.4% children aged 1-6 years, 16.9% infants, 11.3% adults (>60
      years), 8.9% children aged 7-14 years and 1.9% adolescents aged 15-17 years. In
      1.8% the age was not reported. The causal relationship was assessed by the PEI as
      proven in 0.2%, probable in 41.6%, likely in 27.5% and unlikely in 6.6%. In 11.9%
      assessment was not possible and in 11.8% of the reports follow-up information has
      been requested. Comparison to the reports from other sources revealed no major
      difference in respect to quality and content.

PMID- 15583887
TI  - [Thiomersal and immunisations].
AB  - Thiomersal was used in the 1930s for the first time for the preservation of
      vaccines to prevent bacterial and fungal contamination. Thiomersal is an organic
      compound containing 49% mercury (Hg) by weight. It is generally well known that
      mercury and its compounds, including thiomersal, ethylmercury, and methylmercury,
      act as nephro- and neurotoxicants, however, at much higher doses than used in
      vaccines. In the 1990s the question of toxicity of thiomersal in vaccines was
      reassessed since the numbers of vaccines recommended for routine administration
      to infants and children, and therefore the cumulative thiomersal dose in
      children, increased in some countries. Various international committees (European
      Agency for the Evaluation of Medicinal Products, EMEA, US Public Health
      Service/American Academy of Pediatrics, Institute of Medicine, IOM) concluded
      after an extensive risk/benefit analysis that scientific evidence is inadequate
      to reject or explicitly recommend thiomerosal-containing vaccines for children.
      However (in line with the global goal of reducing exposure to mercury), they
      recommended promoting the elimination of thiomerosal from paediatric vaccines.
      This has largely been achieved in Germany. Today a child in Germany can be
      immunised in accordance with the official recommendations (STIKO) almost without
      the administration of thiomerosal (residual amounts). Results of new
      pharmacokinetic and epidemiological studies are discussed. The evidence available
      to date does not support the hypothesis of a potential relationship between
      neurodevelopmental disorders and thiomersal-containing vaccines.

PMID- 15583888
TI  - [Physician's information requirements before providing vaccines].
AB  - Vaccination is one of the most successful and cost-effective tools for disease
      prevention. However, the success makes vaccination its own worst enemy: adverse
      vaccine events, i. e., those caused by the vaccine or those associated with
      immunization by co-incidence or only suspected, become more visible than the
      consequences of the natural disease itself. Not surprisingly, discussions
      regarding the benefit and risk of immunization have become increasingly prominent
      in many industrially developed countries such as Germany. In addition to balanced
      health information provided to the public and the medical community, increased
      attention should be paid to the physician's duty of disclosure before providing
      vaccines. Annually, the German Advisory Committee on Immunization (STIKO)
      publishes updated recommendations on immunization policies including
      recommendations for information requirements. Information should be provided on
      the disease, the nature and benefit of the vaccine, the duration of immunity and
      the need for boosters, possible side effects and complications, and other
      important is-sues. Considering a case of a complication following immunization,
      the German Federal Court of Justice decided recently on the duty of disclosure
      regarding the risk of vaccines. The decision has been taken into consideration by
      the STIKO. Special attention should be paid to information requirements when
      providing licensed but not yet officially recommended vaccines.

PMID- 15583889
TI  - [Vaccine opponents and sceptics. History, background, arguments, interaction].
AB  - Scepticism and critical attitudes towards immunisation have prevailed since the
      introduction of the smallpox vaccine. In Germany the anti-vaccine movement is
      rather small (3-5% of the population). Nevertheless its influence on the
      acceptance of immunisation by the population may be substantial, as shown by the
      examples of smallpox vaccination and the recent discussion of the combined MMR
      vaccine in the UK. Modern societies facilitate networking and the dissemination
      of anti-vaccination ideas. The decline in the incidence of vaccine-preventable
      diseases has led to a reduced awareness of possible complications from infectious
      diseases and to an overestimation of the incidence of rarely occurring adverse
      events following immunisation. Proposals for managing the anti-vaccine movement
      must take into account changes in immunisation policies and draw on elements of
      risk communication.

PMID- 15583890
TI  - [Experiences and difficulties in implementing immunization registries in Saxony
      Anhalt].
AB  - In the German Federal State of Saxony-Anhalt, the Health Department must be
      notified of vaccines administered to children <7 years of age including their
      names. The goal of this mandatory notification is to improve and stabilize the
      age-appropriate vaccination coverage. However, difficulties have been encountered
      in implementing mandatory notification. Therefore, the Health Departments of
      Magdeburg and Halle have launched a model project focusing on analysing and
      eliminating these problems. Mandatory notification requires parents' approval,
      endorsement of vaccantors, and availability of human and technicely resources in
      the Health Department. An enquiry among paediatricians and family doctors in
      private practice revealed widespread reservations about mandatory notification
      because of privacy issues related to data and legal protection. Furthermore,
      family doctors believed that parents disapproved of notification by name.
      However, a survey among young mothers revealed this not to be the case. Winning
      young mothers' approval depends largely on the positive attitude of the
      vaccinators. To implement the mandatory notification of vaccinations to the
      Health Department, it is necessary to dispel physicians' concerns and to inform
      young parents about the practical benefits. However, this places high demands on
      the Health Departments for maintaining immunization registries, communicating
      with physicians and notifying parents when immunisations are due or late.

PMID- 15583891
TI  - [Prevention by vaccination of children and young people. Obstacles and examples
      of effective measures in the Federal State of Brandenburg].
AB  - This article identifies successful vaccination strategies, obstacles to such
      strategies and the role that schools can play in terms of health education by
      analysing vaccination rates among children in the Federal State of Brandenburg.
      The analysis is based on the vaccination status of Brandenburg's children at day
      care centres and schools in relation to the social status of their parents, the
      extent to which preventive examinations (U up to J1) is taken advantage of and
      regional location. Furthermore, an evaluation is rendered of the vaccination
      awareness campaign which has been carried out in sixth grade students since 2002
      to assess the impact of health promotion at schools. In the Federal State of
      Brandenburg vaccination coverage among infants and toddlers is good, with
      approximately 94% having received complete basic vaccination in 2003. By
      contrast, there are marked deficits among tenth grade schoolchildren in terms of
      refresher vaccinations, basic hepatitis B vaccinations and the second measles,
      mumps and rubella (MMR) vaccinations. Vaccination status is strongly dependent on
      the social status of parents and the extent to which preventive medical
      examinations and regional medical health-care provision are utilized. Systematic
      checking of vaccination documents by the public health services promotes
      vaccination awareness. Prevention by vaccination is most effective when combined
      with preventive medical examinations, effective local vaccination management and
      interdisciplinary interventions: education at schools, systematic tracking of
      vaccination documents combined with the provision of vaccinations in doctors'
      surgeries and additionally by the public health services.

PMID- 15583892
TI  - [Immunisation coverage in the adult workforce 2003. Utilisation of routine
      occupational health checks to ascertain vaccination coverage in employees].
AB  - The immunisation campaign from February to December 2003 in the federal state of
      Schleswig-Holstein focused for the first time on the immunisation coverage in
      adults in the workforce. During routine occupational health checks vaccination
      against diphtheria, tetanus, poliomyelitis, measles, mumps, rubella, hepatitis A
      and B (according to vaccination certificates) as well as vaccinations carried out
      on site (active duty) were documented. We received 12,770 anonymous and completed
      questionnaires including 4167 from healthcare workers (with immunisation
      certificate 11,260 and 3776, respectively). The campaign was useful in several
      respects: (1) For the first time data on the immunisation coverage of the active
      work-force became available for Schleswig-Holstein. (2) The acceptance of
      vaccinations by the employees was increased in general and also influenced family
      members. (3) Occupational health physicians can close important gaps in
      immunisation coverage. The results show that (1) immunisation coverage was higher
      in women, young adults and health-care workers and (2) if a vaccine is available,
      then acceptance is also present. Within the joint effort of the continued
      regional vaccination campaign waged since 1999, the previous focus of the
      campaign's activities (children and adolescents) has now had a positive impact on
      vaccination coverage in the age groups under 20 years and up to 29 years.

PMID- 15583893
TI  - [Report of the Robert Koch Institute according to Article 22 of the Transfusion
      Act for the years 2001 and 2002].
AB  - The Robert Koch Institute collects and evaluates data on the prevalence and
      incidence of HIV, hepatitis C (HCV), hepatitis B (HBV) and syphilis infections
      among blood and plasma donors in Germany according to Article 22 of the
      Transfusion Act. The surveillance permits an assessment of the occurrence of
      infections in the blood donor population and consequently the safety of the
      collected donations. This report includes data from all blood donation services
      in Germany for 2001 and 2002. Altogether 5.71 million and 6.63 million donations
      or blood samples from prospective donors were screened in 2001 and 2002,
      respectively. The analysis showed a very low incidence of infections with a
      decreasing trend for HCV infections since 1997 but a slight increase in HIV
      infections in 2001-2002 compared to 1999-2000. The prevalence of the relevant
      infections/100,000 donations was 4.7 for HIV, 94.7 for HCV, 159.0 for HBV and
      33.4 for syphilis in 2001. The rate of seroconversions/100,000 donations was 0.5
      for HIV, 1.6 for HCV, 1.4 for HBV and 1.6 for syphilis in 2001. In 2002 the
      prevalence/100,000 donations was 7.5 for HIV, 97.4 for HCV, 164.1 for HBV and
      31.9 for syphilis. The rate of sero-conversions/100,000 donations in that year
      was 0.7 for HIV, 1.5 for HCV, 1.2 for HBV and 1.9 for syphilis. The quality of
      the reported data has improved significantly compared to previous years. Still,
      some problems remained with the differentiation of the data according to sex, age
      and interval between donations and the reporting by individual blood donation
      centres as required by the Transfusion Act.

PMID- 15583894
TI  - [Vaccination of children and adolescents despite lack of parental approval? A
      discussion of medical responsibility and legal guidelines].

PMID- 15583899
TI  - [Transrectal three dimensional sonography. Techniques and indications].
AB  - In 3-D transrectal ultrasound it is possible, for the first time, to investigate
      the region of interest in three planes simultaneously. Exact examination of the
      organs of the small pelvis as well as of pathologic changes in the region of the
      pelvic floor can be performed with this new imaging technique. The bulbourethral
      glands can be investigated routinely, which enables the diagnosis of cysts of
      these glands. The prostatic zones, their relations as well as the growth of the
      transitional zone during the development of benign prostatic hyperplasia can be
      visualized. Furthermore, 3-D transrectal ultrasound allows investigation of
      morphology and function of the rhabdosphincter. The contractility of the muscle
      can be quantified. 3-D ultrasound guided puncture and drainage of prostatic
      abscesses represents a minimally invasive therapeutic modality. This technique
      can be used to place needles as well as implants in the lower urinary tract.
      Generally, 3-D transrectal ultrasound offers new diagnostic and therapeutic
      possibilities.

PMID- 15583900
TI  - Risk factors and the prevalence of neurosis and psychosis in ethnic groups in
      Great Britain.
AB  - BACKGROUND: Our aim was to examine whether variations in the prevalence of
      neurosis and psychosis between ethnic minorities throughout Great Britain are
      explained by social disadvantage. METHOD: A total of 10,108 adult householders
      throughout Great Britain were assessed in a two-stage survey with the Revised
      Clinical Interview Schedule (CIS-R) and Psychosis Screening Questionnaire (PSQ).
      Respondents with a positive PSQ or who received a diagnosis of, or treatment for,
      psychosis were examined by a psychiatrist using the Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN). Data on respondents' preferred ethnic group
      were collapsed into four groups: Whites, African-Caribbean or Africans, south
      Asians and other. RESULTS: Ethnic grouping was strongly associated with:
      unemployment; lone parent status; lower social class; low perceived social
      support; poverty (indicated by lack of car ownership) and having a primary social
      support group of less than three close others. All these associations applied to
      the group Africans and Afro-Caribbeans, but only some applied to the other
      groups. No ethnic group had significantly increased rates of neurosis. Only the
      African-Caribbean group were at significantly increased risk of a psychotic
      disorder (odds ratio 4.55; 95% CI: 1.13, 18.30). After adjustment for risk
      factors, the odds of psychosis were lower (odds ratio 2.97; 95% CI: 0.66, 13.36).
      CONCLUSIONS: The excess of psychosis in Africans and Afro-Caribbeans in Great
      Britain appears to be partly explained by socio-economic disadvantage, but larger
      studies are needed to confirm this.

PMID- 15583901
TI  - The production and interpretation of disease mapsA methodological case-study.
AB  - BACKGROUND: The study of the spatial variation in disease incidence is a vital
      component of descriptive epidemiology. The production of attractive and
      informative disease maps complements any formal statistical analyses of spatial
      variations and often their visual impact will influence the recipient of the
      information much more than the accompanying statistics. Like any other graphical
      display, however, a map can both inform and mislead. METHODS: We describe
      methodological alternatives and pitfalls for the production of disease maps using
      data on recent suicides in England and Wales as an illustrative example. RESULTS:
      Decisions concerning the methods of mapping of suicide rates, including
      smoothing, choice of grouping criteria and colouring scheme dramatically
      influence the resulting map and how it might be interpreted by the reader.
      CONCLUSIONS: This study provides clinicians and other non-specialist research
      workers an insight into the methodological pitfalls of disease mapping and atlas
      production and should also act as a methodological framework for a critical
      appraisal of published maps and atlases.

PMID- 15583902
TI  - Community perception of mental disorders - a systematic review of Latin American
      and Caribbean studies.
AB  - BACKGROUND: Little is known about the perception of mental disorders and stigma
      in developing countries. The aim of this study was to review the literature on
      popular perception of mental disorders in Latin America and the Caribbean.
      METHODS: Electronic search was made on Medline and Lilacs for original articles
      published from January 1980 to December 2001, using "public attitudes" and
      "mental disorders" as key words on Medline and "attitudes about health" as well
      as "stigma" as key words on Lilacs. In addition, a manual search was conducted in
      the references of the articles obtained in the electronic search and in area
      periodicals. RESULTS: The search produced 871 articles, ten of which fulfilled
      the inclusion criteria. Attitudes in relation to the mentally ill are
      predominantly positive, especially among individuals with a higher educational or
      socioeconomic level. Schizophrenia is the condition most often identified as
      mental illness and considered the most serious affliction. Depression and
      alcoholism are identified as mental illnesses by a smaller portion of the
      population. The community mostly recommends treatment with health professionals.
      CONCLUSION: In Latin America and the Caribbean, there is a tendency to share the
      beliefs of the western medical model and few signs of the presence of elements
      from traditional medicine or religion. However, the studies exhibited various
      methodological gaps and problems. New studies, using more appropriate
      methodology, should be carried out in this region.

PMID- 15583903
TI  - Detection of somatization and depression in primary care in Saudi Arabia.
AB  - BACKGROUND: Studies have shown a high worldwide prevalence of mental disorders in
      primary care. Many patients present with unexplained physical symptoms rather
      than psychological complaints, resulting in an excess number of costly clinical
      investigations. This study investigates the ability of primary care physicians to
      correctly detect and diagnose somatization and depression in Saudi Arabian
      patients. METHODS: In all 431 primary care patients in Riyadh Saudi Arabia were
      screened for somatization and depression using the Patient Health Questionnaire
      (PHQ). Primary care physicians independently assessed these same patients while
      blinded to the results of the PHQ. Agreement between physician observations and
      the screening instrument was examined. RESULTS: Using the PHQ as the standard of
      comparison for measuring the detection rates of Saudi physicians, the agreement
      between and the PHQ and physician assessments was kappa = 0.40 for depression
      (0.45 females, 0.31 males) and kappa = 0.27 for somatization (0.36 females, 0.12
      males). Physicians assessed higher rates of somatization than indicated by the
      screening instrument and demonstrated poor diagnostic agreement on somatization
      and depression, particularly for male patients. CONCLUSIONS: Saudi primary care
      physicians have awareness of psychiatric disorders, but their diagnostic skills
      are poor for somatization and depression. Psychiatric training should be
      supported in the continuing education of primary care physicians and patients
      should be encouraged to report psychological complaints to family physicians. A
      simple screening instrument for identifying mental disorders in developing
      countries is a valuable tool for assessment in primary care.

PMID- 15583904
TI  - The phenomenon of somatization among community Chinese Americans.
AB  - OBJECTIVE: The phenomenon of somatization was explored in relation to the
      experiences of acculturation, stress, support, and distress. METHODS: A
      representative community sample of 1,747 Chinese Americans (aged 18-65 years),
      selected by a multi-stage household sampling design, in the Los Angeles County
      was interviewed to tap their psychiatric diagnoses, symptomatology, level of
      acculturation, stress, and support. RESULTS: Across all indices, Chinese
      Americans' level of somatic symptoms, impairment related to somatization, and
      percentage of meeting the Somatic Symptom Index 5/5 (SSI 5/5) criterion were
      comparable to those found in other populations. Length of residence in the U. S.
      and acculturation were not related to somatization. Regression analyses showed
      that anxiety, depression, gender, age, education, stressors, and support were
      significantly related to somatization, ps < 0.05. Somatizers tended to perceive
      themselves with poor health and utilized both Western and indigenous Chinese
      medicine. CONCLUSION: The importance of demographics, psychological distress, and
      stress was emphasized in the explanation of somatization tendencies among
      immigrant Chinese Americans. Somatization might be a stress response with regard
      to increased distress severity and psychosocial stressors rather than a cultural
      response to express psychological problems in somatic terms.

PMID- 15583905
TI  - Depressive symptomatology in pregnancy - a Singaporean perspective.
AB  - This is a two-part study looking at depressive symptomatology in pregnancy in
      Singaporean women, and the associated demographic, and bio-psychosocial
      characteristics of women at risk of depressive illness. We validated the 10-item
      Centre for Epidemiological Studies-Depression scale amongst pregnant women, and
      then used this tool to identify depressive states in an antenatal cohort from the
      national maternity hospital. Amongst the sample population, the rate of
      depressive disorders is as high as one in five in the antepartum. The risk
      factors in the antepartum include being young, history of smoking, having past
      and current obstetric complications, frequent alcohol use and having medical
      problems.

PMID- 15583906
TI  - Personality, perceived parental rejection and problem behavior in adolescence.
AB  - BACKGROUND: It has been well documented that adolescents run a heightened risk
      for developing depression and aggression when they feel rejected by their parents
      and that parental rejection has different effects for gender in developing
      depression and aggression. Whether personality in combination with gender plays a
      role in the association between parental rejection, depression and aggression has
      not yet received much attention. METHOD: This was a cross-sectional study using
      data from the Conflict and Management of Relationships study (CONAMORE). A total
      of 1142 early and middle adolescents completed questionnaires about parental
      rejection, depression, aggression and personality. The associations between the
      variables were tested in multi-group moderation models using structural equation
      modeling. RESULTS: Perceived parental rejection was associated with depression
      and aggression in most of the combined personality type and gender groups.
      Personality type and gender moderated the associations between perceived parental
      rejection, depression and aggression. Several clear differences between the
      combined personality type and gender groups were found on these associations.
      CONCLUSION: Several clear moderating effects of the personality type x gender
      groups were found on associations between perceived parental rejection,
      depression and aggression. Future research should focus on these specific
      combinations instead of using either personality types or gender separately.

PMID- 15583907
TI  - Help-seeking for mental health problems among young physicians: is it the most
      ill that seeks help? - A longitudinal and nationwide study.
AB  - OBJECTIVES: The aims of this study were to assess the prevalence of self-reported
      mental health problems and help-seeking among young physicians, and identify
      predictors of seeking help. METHODS: A prospective cohort sample of Norwegian
      medical students (N = 631) were assessed in their final semester (T1), and in the
      first (T2) and fourth (T3) postgraduate year. The average observation period was
      3.6 years. RESULTS: The prevalence of mental health problems that needed
      treatment over the preceding year was observed to have increased from 11% at T2
      to 17% at T3. There was no increase in help-seeking. Longitudinally, 34% reported
      that they needed treatment on one or several occasions. Adjusted predictors of
      help-seeking were perceived level of mental health problems and a reality
      weakness personality trait. CONCLUSION: Those who sought help had higher levels
      of emotional distress than those who did not. However, higher reality weakness
      scores predicted lower help-seeking and, therefore, may be a risk factor for
      avoiding necessary care.

PMID- 15583908
TI  - Life satisfaction and depression in a 15-year follow-up of healthy adults.
AB  - OBJECTIVE: The aim of this study was to investigate the cross-sectional and
      longitudinal relationship between life satisfaction and depressive symptoms in
      healthy adults. METHOD: This is a 15-year prospective cohort study with a
      nationwide sample of healthy Finnish adults (N = 9679), aged 18-45, who responded
      to postal questionnaires in 1975, 1981 and 1990 including a 4-item life
      satisfaction (LS) scale (range 4-20) and, in 1990, the 21-item Beck Depression
      Inventory (BDI). RESULTS: A strong linear association was found between
      concurrent LS and BDI scales (r = 0.6). With an LS cut-off point of 11/12,
      moderate/severe depression (BDI > or = 19) was detected with 87% sensitivity, 88
      % specificity and a 94% area under the ROC curve. Longitudinally, a strongly
      increased risk of moderate/severe depression in 1990 was observed among the
      dissatisfied (LS 12-20) compared with the satisfied (LS 4-6) in 1975 (OR = 6.7;
      95 %CI 4.2-10.9) and in 1981 (OR = 10.4; 6.1-17.6). CONCLUSION: The 4-item LS
      scale can identify a group of healthy people from the general population with a
      high risk of having or developing depressive symptoms. Since low life
      satisfaction also indicates an elevated risk of other adverse health outcomes,
      the assessment of subjective well-being should be encouraged both in surveys and
      in clinical practice.

PMID- 15583909
TI  - Social exclusion and risk of emergency compulsory admission. A case-control
      study.
AB  - BACKGROUND: Emergency detentions under section 4 of the Mental Health Act 1983
      are more frequent in socially deprived areas of England and Wales. However, it is
      not clear whether individual socio-economic disadvantage increases likelihood of
      emergency detention. Therefore, this study tests the hypothesis that a higher
      proportion of people who are socially excluded will be admitted to hospital under
      section 4 than those who are not. METHODS: A total of 300 mental health act
      assessments in two London boroughs with different rates of section 4 admissions
      were studied by retrospective case note review in a case-control design. An index
      of social exclusion was created and piloted for this study. RESULTS: The logistic
      regression analysis discovered four risk factors for section 4 admissions:
      presenting with a risk to self or others at the mental health act assessment, bi
      polar affective disorder, non-White British ethnicity and low social support.
      There were no significant differences between the two boroughs on these
      variables. Risk factors for any compulsory admission were: presenting with a
      risk, psychosis and non-White British ethnicity. CONCLUSION: This study found low
      social support to be the only social exclusion indicator that increases
      likelihood of admission under section 4. While individual-level variables explain
      some of the variation in section 4 rates, it is likely that, as indicated by
      other studies, different configurations of mental health services affect rates to
      a greater degree.

PMID- 15583910
TI  - Public attitudes to depression in urban Turkey - the influence of perceptions and
      causal attributions on social distance towards individuals suffering from
      depression.
AB  - BACKGROUND: The aim of this study was to determine public attitudes towards
      patients with depression and the influence of perception and causal attributions
      on social distance towards individuals suffering from depression in urban areas.
      METHODS: This study was carried out with a representative sample in Istanbul
      which is the biggest metropolis in Turkey. Seven hundred and seven subjects
      completed the public survey form which consisted of ten items screening the
      demographic features and health status of the participants, and 32 items rating
      attitudes towards depression. RESULTS: The respondents' attitudes towards
      depression were very negative and nearly half of the subjects perceived people
      with depression as dangerous. More than half of the subjects stated that they
      would not marry a person with depression, and nearly half of the subjects stated
      that they would not rent their house to a person with depression. One-quarter of
      the subjects stated that depressive patients should not be free in the community.
      The subjects who considered depression as a disease and who believed that
      weakness of personality and social problems cause depression had negative
      attitudes towards depression. CONCLUSIONS: In Istanbul, people recognise
      depression well, but their attitudes towards it are fairly negative. The urban
      public has unfavourable attitudes towards depression and a tendency to isolate
      patients from the society. Notwithstanding the high prevalence, there is still
      considerable stigmatisation associated with depression.

PMID- 15583911
TI  - Influence of diagnostic classification on gender ratio in schizophrenia - a meta
      analysis of youths hospitalized for psychosis.
AB  - BACKGROUND: The research literature on hospital admissions for psychoses in
      youths was reviewed in order to test whether there was a gender ratio discrepancy
      in diagnostic subgroups; the effect of the diagnostic criteria classification on
      this measure was also investigated. METHOD: A meta-analysis was conducted on 12
      primary studies by assessing the male/female odds ratio (OR) in the schizophrenia
      and mood disorders with psychosis subgroups as well as the amount of variability
      between studies. Study inclusion criteria were: patients between the ages of 8
      and 19, at least 15 patients with psychosis and a standardized diagnostic
      criteria classification system such as DSM, ICD or RDC. RESULTS: The male/female
      OR measured in this meta-analysis implies that a male subject with psychosis is
      1.7 times as likely to obtain a diagnosis of schizophrenia; conversely, a female
      subject with psychosis is 2.1 times as likely to be assigned in the mood
      disorders with psychosis subgroup. Disparity in diagnostic criteria nomenclature
      (ICD-9 vs. DSM) could account for a statistically significant difference in
      male/female OR for the schizophrenia subgroup in a subset of 11 studies.
      CONCLUSIONS: Under the narrower definition of schizophrenia in studies using DSM
      diagnostic criteria classification, the shift towards a greater proportion of
      patients diagnosed with mood disorders with psychosis could be explained by the
      time criteria; the simultaneous emergence of the gender ratio difference is
      discussed. This study shows that subtle changes in diagnostic criteria in
      psychiatric illnesses can greatly influence observational data pertaining to
      youths.

PMID- 15583912
TI  - Receptor function reserve: a new parameter for disease detection.

PMID- 15583913
TI  - Prognostic value of fatty acid imaging in patients with angina pectoris without
      prior myocardial infarction: comparison with stress thallium imaging.
AB  - A fatty acid analogue, 123I-labelled beta-methyl iodophenyl pentadecanoic acid
      (BMIPP), has been used to identify ischaemic and metabolically impaired
      myocardium. However, the prognostic value of BMIPP imaging, particularly in
      relation to stress myocardial perfusion imaging, remains unclear. Data from 167
      consecutive patients with angina pectoris but without prior myocardial infarction
      (MI) who had undergone both BMIPP and stress 201Tl (sTL) imaging were analysed.
      Tracer uptake was graded using a 13-segment, 4-point scoring model. Patients were
      followed up for 48 months with primary end points (cardiac death, non-fatal MI)
      as hard cardiac events and with secondary end points (late revascularisation,
      recurrent angina and heart failure) as soft events. For overall cardiac events (5
      hard and 29 soft events), Kaplan-Meier analysis revealed significantly lower
      event rates in subgroups with normal BMIPP uptake, a summed difference score of
      sTL (SDS) of <3 or absence of diabetes mellitus when compared to each
      counterpart. Multivariate Cox's analysis revealed reduced BMIPP uptake, SDS > or
      =3, diabetes and reduced ejection fraction to be significant predictors. Negative
      predictive values of normal BMIPP and SDS <3 for all events were 91% and 84%,
      respectively. No hard event occurred in 66 patients with normal BMIPP uptake,
      whereas two patients with SDS <3 but impaired BMIPP uptake had hard events. In
      conclusion, normal BMIPP imaging is an excellent prognostic sign, independently
      of stress myocardial perfusion imaging, in patients with angina pectoris without
      prior MI.

PMID- 15583914
TI  - Imaging of dopamine transporters and D2 receptors in patients with Parkinson's
      disease and multiple system atrophy.
AB  - PURPOSE: The aim of this study was to ascertain whether combined presynaptic and
      postsynaptic dopaminergic single-photon emission computed tomography (SPECT)
      scanning is useful for differentiation between patients with idiopathic
      Parkinson's disease (IPD), patients with multiple system atrophy of the
      striatonigral type (MSA) and healthy subjects. METHODS: SPECT measurements of the
      dopamine transporter (DAT) were done with 123I-beta-CIT, while for determination
      of the dopamine D2-like receptors (D2), 123I-epidepride was used. Clinical
      evaluation and SPECT scans were carried out in 14 patients with IPD, eight
      patients with MSA and 11 healthy age-matched control subjects. RESULTS: Putaminal
      DAT binding was reduced to 32% of control values in IPD and to 19% of control
      values in MSA . Significantly higher striatal asymmetry in DAT binding was found
      in MSA than in controls, but IPD patients had significantly higher asymmetry than
      MSA patients. Striatal D2 binding did not differ significantly between patients
      and healthy controls but the ratio between caudate DAT and D2 binding was
      significantly higher in patients with IPD than in those with MSA, even when
      disease severity was taken into account. CONCLUSION: Patients with reduced
      striatal 123I-beta-CIT binding and a side-to-side difference greater than 15% are
      likely to suffer from IPD. Patients with reduced striatal 123I-beta-CIT binding
      and a side-to-side difference of between 5% and 15% are more likely to have MSA.
      123I-epidepride SPECT measurements may add further diagnostic information, since
      the ratio between DAT and D2 receptor binding is significantly higher in IPD than
      in MSA.

PMID- 15583916
TI  - Age and gender related differences in children's evaluation of procedures
      experienced during participation in clinical research.

PMID- 15583917
TI  - Serological screening for undiagnosed coeliac disease in male adolescents in
      lower Austria: a population based study.

PMID- 15583918
TI  - Effect of recombinant human bone morphogenetic protein-2 on the osseointegration
      of dental implants: a biomechanics study.
AB  - BACKGROUND: Bone augmentation procedures in combination with dental implants
      enhance osseointegration in areas that demonstrate localized bone deficit.
      Clinical confirmation of a biomechanically stable interface is essential for
      functional implant loading. PURPOSE: The aim of this study was to evaluate
      biomechanically the effect of recombinant human bone morphogenetic protein
      (rhBMP)-2 on implant osseointegration and correlate it with periotest and
      radiographic measurements. MATERIALS AND METHODS: Hollow cylinder implants were
      filled with absorbable collagen sponge soaked with rhBMP-2 or left empty and
      implanted in dog mandibles. The animals were followed for 4, 8, and 12 weeks,
      periotest assessment was performed at the end of each time interval, and
      specimens were collected for pullout biomechanical testing and radiographic
      evaluation of bone-implant contact levels. RESULTS: Periotest assessment did not
      provide evidence of statistically significant differences between the two groups
      and correlated well with the radiographic bone-implant contact levels. The
      pullout test revealed a higher correlation between force/displacement and
      displacement/energy for the experimental group, suggesting that the addition of
      rhBMP-2 did influence the rate of osseointegration. CONCLUSION: The results from
      the pullout test support the potential role of rhBMP-2 in clinical applications
      by promoting a biomechanically mature interface at 12 weeks. However,
      radiographic and periotest assessment of the bone-implant interface did not
      provide evidence of the differences observed with biomechanical testing.

PMID- 15583919
TI  - The safety and efficacy of a powered toothbrush on soft tissues in patients with
      implant-supported fixed prostheses.
AB  - The safety, efficacy and acceptability of an oscillating/rotating powered
      toothbrush was assessed in patients rehabilitated with fixed prostheses on
      implants. One hundred consecutive patients (aged 18-80; mean 56.3; 51 females),
      who met the inclusion/exclusion criteria and who participated in a regular annual
      recall scheme, were enrolled. They were instructed on how to use the powered
      toothbrush, as well as on classical interdental plaque control. The electric
      toothbrush had to be used twice daily for 2 min. The following periodontal
      parameters were measured at baseline and at 3 months, 6 months and 12 months:
      presence/absence of gingival and/or mucosal ulceration/desquamation; sulcus
      bleeding index; probing pocket depth; periodontal pocket-bleeding index and
      gingival recession. At 3 months and at the end of the study, patients completed a
      questionnaire concerning the overall acceptability and convenience of the powered
      toothbrush, as compared with their habitual manual toothbrush. A total of 80
      patients completed the study. No dropouts were related to the use of the powered
      toothbrush. All parameters improved over the course of the study. The mean
      overall pocket depth decreased from 3.3 mm at baseline to 3.0 mm at 12 months,
      while the mean decrease in recession was 0.1 mm at 12 months. During the 1-year
      observation, there was a slight gain in periodontal attachment level. Gingival
      ulcerations were not observed at any point in the study. High scores for
      convenience and comfort of the powered toothbrush were reported, and the majority
      (95%) said that they would continue to use it for habitual oral hygiene. It is
      concluded that the powered toothbrush investigated is effective, safe and
      comfortable for patients rehabilitated by means of oral implant-supported
      prostheses.

PMID- 15583920
TI  - GTR treatment of intrabony defects with PLA/PGA copolymer or collagen
      bioresorbable membranes in combination with deproteinized bovine bone (Bio-Oss).
AB  - The objectives of this study were to evaluate the results of guided tissue
      regeneration (GTR) treatment of intrabony defects with two kinds of bioresorbable
      membranes, with deproteinized bovine bone (Bio-Oss) used as an adjunct. Twenty
      eight patients with at least one intrabony defect with a probing pocket depth
      (PPD) >/=7 mm and radiographic evidence of an intrabony component (IC) >/=4 mm
      were randomly treated with either a polylactic/polyglycolic (PLA/PGA) acid
      copolymer or a collagen bioresorbable membrane combined with Bio-Oss
      implantation. Immediately prior to surgery (baseline) and after 1 year, the
      following parameters were recorded: (1) PPD, (2) gingival recession (REC), (3)
      probing attachment level (PAL), (4) presence/absence of plaque (PI), and (5)
      presence/absence of bleeding on probing (BOP). Occurrence of membrane exposure
      during healing and the smoking habits of the patients were also recorded.
      Statistical analysis was carried out using chi(2) -tests and t-tests. There were
      no significant differences between the two membrane groups regarding the clinical
      parameters at baseline. Statistically significant clinical improvements (PAL
      gains, reduced PPDs) were observed 1 year after treatment in both groups. There
      were no significant differences, however, between the PLA/PGA and the collagen
      membrane groups regarding any of the evaluated parameters (mean PAL gain: 2.9 mm
      vs 3.9 mm; mean residual PPD: 4.8 mm vs 4.1 mm, respectively). The membrane
      material per se does not seem to be a critical factor for the outcome of GTR
      treatment of intrabony defects with bioresorbable membranes.

PMID- 15583923
TI  - [Long-term results following reconstruction of maxillary sinus wall defects with
      titanium micro-mesh: a CT-based study].
AB  - BACKGROUND: Extensive bony defects of maxillary sinus walls have to be
      reconstructed to prevent long-term complications. Different autogenous,
      allogeneic, and alloplastic materials, e.g., titanium mesh, are used for
      reconstruction. MATERIAL AND METHODS: In 26 patients large defects of the facial
      and laterodorsal walls of the maxillary sinus were reconstructed using titanium
      micro-mesh. The mean follow-up period was 49 months (5 months-10 years). All
      patients were examined with computed tomography applying multiplanar
      reconstruction techniques and three-dimensional volume rendering. RESULTS: In the
      CT scans stable scars of 3-6 mm thickness could be found on the antral surfaces
      of all titanium meshes bridging the defects. In 70% of the patients the volume of
      the reconstructed maxillary sinus reached 80-100% of the contralateral side.
      Volume losses were not due to poor adaptation of the titanium mesh but were
      caused by thickening of maxillary sinus walls or traumatic malpositions. In 77%
      of the patients ventilation of the maxillary sinus was undisturbed. After mesh
      removal neither facial contour disturbances nor changes of sinus volume were
      noted. Soft tissue invasion into the sinus was prevented by a stable scar which
      had formed underneath the mesh. Three-dimensional reconstruction confirmed
      symmetrical facial contours in all patients. CONCLUSIONS: The titanium micro-mesh
      offers a simple and effective alternative to autogenous tissue with stable long
      term results for reconstruction of large maxillary sinus wall defects.

PMID- 15583924
TI  - [Antimicrobial photodynamic therapy for prevention of alveolar ostitis and post
      extraction pain].
AB  - AIM: Alveolar ostitis occurs with an incidence of 3-25% after tooth extraction.
      Antimicrobial photodynamic therapy (aPDT) with HELBO Blue and TheraLite laser
      enables local decontamination of the extraction socket. The aim of the study was
      to evaluate the possibility of aPDT with HELBO Blue and diode soft laser to
      reduce the prevalence of alveolar ostitis. MATERIAL AND METHODS: In an
      intraindividual study with 100 patients in 130 jaws, one or multiple
      contralateral teeth were removed at 1-week intervals. Randomly each side was
      treated with or without aPDT with a standardized protocol. At recall the
      evaluation of the extraction socket was performed by the investigator and the
      postoperative pain sensation was judged by the patient on an analog pain scale (0
      100). RESULTS: In the group with aPDT alveolar ostitis occurred at one extraction
      site and in the control group without aPDT in 13 cases. The subjective pain
      assessment on the day after tooth removal was scored with 11.2+/-9.8 in the aPDT
      group and with 19.0+/-12.2 in the control group. One week after extraction the
      pain sensation in the aPDT group was scored with 2.4+/-9.2 and in the control
      group with 13.1+/-25.2. The difference was significantly lower with p=0.000 for
      the 1st and 8th post-surgical days in the aPDTgroup. CONCLUSIONS: The
      significantly lower incidence of alveolar ostitis after antimicrobial
      photodynamic therapy seems to be a new and promising possibility for the
      prevention of alveolar ostitis.

PMID- 15583925
TI  - [Otological findings in adults with isolated cleft palate or cleft lip, jaw, and
      palate].
AB  - BACKGROUND: Children with cleft palate often develop middle ear ventilation
      disorders due to chronic Eustachian tube dysfunction. This may lead to hearing
      loss. The insertion of ventilation tubes is a widely accepted measure to avoid
      sequelae of middle ear ventilation disorders and hearing loss. On the other hand,
      long-term therapy with ventilation tubes may inflict iatrogenic complications.
      The objective of the study was the evaluation of otoscopic and audiometric long
      term findings in adult cleft patients who had been treated with ventilation tubes
      since childhood when chronic otitis media with effusion had been observed.
      PATIENTS AND METHODS: Ninety-two cleft palate patients had been followed up
      otoscopically and audiometrically for years. The average age was 19.3 years
      (minimum: 14, maximum: 39 years) at the time the last status was taken. RESULTS:
      Otoscopy revealed a perforation of the tympanic membrane in 3.8% of the 184 ears.
      12% of the patients developed cholesteatoma, however three quarters of these
      occurred after age 11. 86.4% of the 92 patients had normal hearing in pure tone
      audiometry. CONCLUSION: Compared with adult cleft patients who did not receive
      ventilation tubes, our patients had a similar low incidence of eardrum
      perforations but a higher incidence of cholesteatomas while hearing loss occurred
      less often. Whether the higher incidence of cholesteatomas is caused
      iatrogenically or due to a longer follow-up period remains unclear. Whether the
      use of long-lasting ventilation tubes affects the incidence of cholesteatomas
      must be proved in further studies.

PMID- 15583926
TI  - [Preoperative autologous blood donation in orthognathic surgery].
AB  - AIM: To minimize the perioperative risk of transfusion-associated complications,
      preoperative autologous blood donation is routinely performed in orthognathic
      surgery. This study critically analyzed the necessity of this procedure with
      respect to clinical, economic, and juridical issues. MATERIAL AND METHODS: In the
      Department of Oral and Maxillofacial Surgery, Bonn Medical School, 178
      orthognathic surgical procedures were performed from 1994 to 2002. All patients
      (women, n=101; men, n=77) were informed about the possibility of autologous blood
      donation. This procedure was carried out in 83%, for single jaw surgery two and
      for bimaxillary osteotomies three to four units of packed red blood cells were
      predeposited. Of the patients, 99 underwent monognathic surgery in the lower jaw,
      27 patients in the upper jaw, and bimaxillary osteotomy was performed in 52
      patients. RESULTS: The average blood loss for the monognathic procedure in the
      lower jaw was 756 ml, in the upper jaw 858 ml, and in double jaw surgery 1391 ml.
      In 13 patients the hemoglobin concentration fell below 7.5 g/dl and 12 patients
      received their predeposited autologous blood units. A total of 57.7% of all
      donated autologous blood units were discarded. CONCLUSION: Autologous blood
      donation should be performed from the medical point of view for double jaw
      surgery and considered in single cases with special risks in monomaxillary
      osteotomies.

PMID- 15583927
TI  - [Modified submental endotracheal intubation in concurrent orthognathic surgery].
AB  - BACKGROUND: In 1986 Altemir described a method of submental endotracheal
      intubation in order to avoid tracheostomy in maxillofacial trauma cases where
      short-term intermaxillary fixation was required. His method has become widely
      established for airway maintenance in midfacial fractures. CASE: We present a 21
      year-old male patient with cleft lip and palate on the left side. The patient
      underwent Le Fort I maxillary osteotomy. Nasal intubation was impossible due to
      nasal malformation. In this case we used submental endotracheal intubation for
      airway maintenance. We introduced new methods: a sterile nylon guiding tube and
      our new "2-2-2 rule" incision to make the procedure easier. RESULTS: The
      occlusion could be checked easily. There were no complications during and after
      the operation. The submental wound healed nicely. DISCUSSION: The described case
      shows that the technique is easy to use compared to "alternative" intubation
      methods. Submental scarring is acceptable. We recommend the technique for
      orthognathic use.

PMID- 15583929
TI  - Immunological and morphogenic basis of gastric mucosa atrophy and metaplasia.
AB  - Chronic gastritis with gastric mucosa atrophy, intestinal metaplasia and
      endocrine cell hyperplasia are alterations with an increased risk for the
      development of gastric neoplasias. Immunological studies in autoimmune gastritis,
      in atrophic Helicobacter pylori gastritis and in studies with transgenic mice
      point to a central role of the parietal cell in the development of gastric mucosa
      atrophy. Destruction of gastric epithelial cells alone might not be sufficient
      for the loss of complete gastric glands. Gastric atrophy, endocrine cell
      hyperplasia and intestinal and pancreatic metaplasia can be regarded as the
      result of altered morphogenesis within the gastric mucosa. Impaired expression of
      the gastric morphogenic factor Sonic Hedgehog by parietal cells and increased
      expression of the transcriptional activators of intestinal and pancreatic
      differentiation, namely CDX2 and PDX1, seem to be crucial for the development of
      gastric atrophy and for intestinal, endocrine and pancreatic transdifferentiation
      processes. Altered expression of these morphogenic factors is partly caused by
      changes in the gastric milieu. Further studies concerning the normal and
      pathological morphogenesis of the gastric mucosa and related tissues might give
      new insight into the pathogenesis of gastric atrophy and metaplasia.

PMID- 15583930
TI  - Discovery of a letter from Rokitansky to Virchow about subependymal corpora
      amylacea.
AB  - Until recently, Rokitansky and Virchow were thought to have never exchanged
      letters. Recently, however, a letter from Rokitansky to Virchow dated 1853 was
      discovered. In this letter, Rokitansky commented on Virchow's discovery of
      subependymal corpora amylacea. This report comprises an English translation of
      this letter together with a historical appraisal and a short comment on the
      importance of corpora amylacea in the brain.

PMID- 15583931
TI  - Ciliated hepatic foregut cyst communicating with the gallbladder.

PMID- 15583932
TI  - Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the
      second trimester of gestation. Is diagnosis from fetal autopsy possible?
AB  - Chorioamnionitis, as the most frequent cause of second trimester abortions, is
      commonly diagnosed by histomorphological examination of placental tissue. We
      determined whether chorioamnionitis induces a fetal extramedullary hematopoietic
      response and estimated whether chorioamnionitis can be diagnosed from fetal liver
      alone. Clinical data and morphological and histological findings of 39 second
      trimester abortions, caused by chorioamnionitis, were compared with 32 age
      matched control cases. Using hematoxylin and eosin staining, naphtol-ASD
      chloracetate esterase and "Berliner Blau" reaction, total hematopoiesis,
      erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were
      examined. In the study group, total hematopoiesis was increased compared with the
      controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus
      56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal
      myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were
      located predominantly intrasinusoidal and periportal (74.4%), while an isolated
      periportal location was often observed in controls (50.0%). Isolated perivenous
      iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and
      correlated with the increasing severity of chorioamnionitis. It can be stated
      that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic
      myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic
      hematopoiesis and iron storing might also be helpful in the diagnosis of
      chorioamnionitis, especially when the placenta is not available for examination.

PMID- 15583933
TI  - Carcinoma ex-pleomorphic adenoma of the breast. Report of three cases suggesting
      a relationship to metaplastic carcinoma of matrix-producing type.
AB  - Three cases of carcinoma ex-pleomorphic adenoma of the breast are reported.
      Patients were 82, 60 and 56 years old and presented with a breast lump. All
      tumours showed areas of pleomorphic adenoma adjacent to typical areas of
      malignant transformation. These cases add to the spectrum of tumours shared by
      breast and salivary gland. The relationship between these neoplasms and
      metaplastic carcinoma of matrix-producing type is discussed.

PMID- 15583934
TI  - Subclinical chorioamnionitis: an unrecognised risk factor for severe pulmonary
      haemorrhage in extremely low birth weight infants.

PMID- 15583935
TI  - Anti-angiogenic effects of SN38 (active metabolite of irinotecan): inhibition of
      hypoxia-inducible factor 1 alpha (HIF-1alpha)/vascular endothelial growth factor
      (VEGF) expression of glioma and growth of endothelial cells.
AB  - PURPOSE: Inhibition of angiogenesis is an important new treatment modality for
      malignancies, including gliomas. Vascular endothelial growth factor (VEGF) and
      hypoxia inducible factor-1alpha (HIF-1alpha) have been investigated as potent
      mediators of tumor angiogenesis. We investigated whether four major
      chemotherapeutic agents (ACNU, cisplatin, etoposide, and SN38) showed an
      angiosuppressive effect in vitro. METHOD: The effects of ACNU, cisplatin,
      etoposide, and SN38 for endothelial cells were assessed by cell growth inhibition
      assay (WST-8 assay) and vessel formation assay (angiogenesis kit). The inhibitory
      effects of the HIF-1alpha and VEGF expression of glioma cells after SN38
      treatment were assessed by real-time RT-PCR, Western blot, and ELISA. RESULTS:
      SN38, but not other chemotherapeutic agents, selectively inhibited endothelial
      cell proliferation and three-dimensional tube formations at the 0.01 microM.
      Furthermore, SN38 significantly decreased the HIF-1alpha and VEGF expression of
      glioma cells in a dose- and time-dependent manner under normoxic and hypoxic
      conditions. SN38 has dual angiosuppressive actions, including both the inhibition
      of endothelial proliferation and tube formation, and the inhibition of the
      angiogenic cascade in glioma cells. CONCLUSION: SN38 is an attractive agent as
      both a direct and indirect angiogenesis inhibitor and provides the anti-glioma
      agents with an angiosuppressive function.

PMID- 15583936
TI  - Comparison of lenograstim and filgrastim: effects on blood cell recovery after
      high-dose chemotherapy and autologous peripheral blood stem cell transplantation.
AB  - PURPOSE: The aim of the study was to evaluate whether glycosylated granulocyte
      colony-stimulating factor (G-CSF) (lenograstim) offers a benefit over non
      glycosylated G-CSF (filgrastim) in clinically relevant end points after high-dose
      chemotherapy (HDC) and autologous peripheral blood stem cell transplantation
      (PBSCT). METHODS: We retrospectively analyzed the outcome of 261 patients treated
      with either lenograstim (n=68) or filgrastim (n=193). Time to blood cell
      recovery, toxicities, and infectious complications were analyzed in a total of
      469 G-CSF treatment cycles. RESULTS: Mean time to leukocyte recovery was 10.7
      days (SD+/-0.9) (lenograstim) and 10.8 days (SD+/-0.6) (filgrastim),
      respectively. Likewise, time to thrombocyte engraftment, febrile days, duration
      of therapeutic antibiotic treatment, severity of non-hematological toxicities,
      duration of in-hospital stay, and duration of G-CSF treatment were similar in
      both groups. Owing to the physicochemical and pharmacokinetic properties of
      lenograstim, the required dose until leukocyte recovery was significantly smaller
      as compared to filgrastim (38.5 vs 54.0 microg/kg of body weight). CONCLUSIONS:
      Collectively, our data indicate that both G-CSF preparations are equally
      effective in hastening leukocyte recovery in the setting of high-dose
      chemotherapy followed by autologous PBSCT.

PMID- 15583937
TI  - Validity reassessment of Trichobilharzia species using Lymnaea stagnalis as the
      intermediate host.
AB  - The systematics within the genus Trichobilharzia is complicated. After the
      description of the type species Trichobilharzia ocellata, the name was routinely
      used for nearly all European findings of ocellate furcocercariae. T. ocellata was
      also described from North America and Japan. However, the identity of T. ocellata
      remains questionable. Comparison of data from the literature showed differences
      among various T. ocellata isolates and led us to the conclusion that the North
      American and the Japanese findings are not identical with European T. ocellata.
      In addition, the description of T. szidati corresponds with the recently reported
      European T. ocellata isolates. Sequence analysis of the ITS region confirmed that
      they are identical.

PMID- 15583938
TI  - The complete nucleotide sequence and multipartite organization of the tobacco
      mitochondrial genome: comparative analysis of mitochondrial genomes in higher
      plants.
AB  - Tobacco is a valuable model system for investigating the origin of mitochondrial
      DNA (mtDNA) in amphidiploid plants and studying the genetic interaction between
      mitochondria and chloroplasts in the various functions of the plant cell. As a
      first step, we have determined the complete mtDNA sequence of Nicotiana tabacum.
      The mtDNA of N. tabacum can be assumed to be a master circle (MC) of 430,597 bp.
      Sequence comparison of a large number of clones revealed that there are four
      classes of boundaries derived from homologous recombination, which leads to a
      multipartite organization with two MCs and six subgenomic circles. The mtDNA of
      N. tabacum contains 36 protein-coding genes, three ribosomal RNA genes and 21
      tRNA genes. Among the first class, we identified the genes rps1 and psirps14,
      which had previously been thought to be absent in tobacco mtDNA on the basis of
      Southern analysis. Tobacco mtDNA was compared with those of Arabidopsis thaliana,
      Beta vulgaris, Oryza sativa and Brassica napus. Since repeated sequences show no
      homology to each other among the five angiosperms, it can be supposed that these
      were independently acquired by each species during the evolution of angiosperms.
      The gene order and the sequences of intergenic spacers in mtDNA also differ
      widely among the five angiosperms, indicating multiple reorganizations of genome
      structure during the evolution of higher plants. Among the conserved genes, the
      same potential conserved nonanucleotide-motif-type promoter could only be
      postulated for rrn18-rrn5 in four of the dicotyledonous plants, suggesting that a
      coding sequence does not necessarily move with the promoter upon reorganization
      of the mitochondrial genome.

PMID- 15583939
TI  - Demography in relation to population density in two herbivorous marsupials:
      testing for source-sink dynamics versus independent regulation of population
      size.
AB  - We compared demography of populations along gradients of population density in
      two medium-sized herbivorous marsupials, the common brushtail possum Trichosurus
      vulpecula and the rufous bettong Aepyprymnus rufescens, to test for net dispersal
      from high density populations (acting as sources) to low density populations
      (sinks). In both species, population density was positively related to soil
      fertility, and variation in soil fertility produced large differences in
      population density of contiguous populations. We predicted that if source-sink
      dynamics were operating over this density gradient, we should find higher
      immigration rates in low-density populations, and positive relationships of
      measures of individual fitness--body condition, reproductive output, juvenile
      growth rates and survivorship--to population density. This was predicted because
      under source-sink dynamics, immigration from high-density sites would hold
      population density above carrying capacity in low-density sites. The study
      included 13 populations of these two species, representing a more than 50-fold
      range of density for each species, but we found that individual fitness,
      immigration rates and population turnover were similar in all populations. We
      conclude that net dispersal from high to low density populations had little
      influence on population dynamics in these species; rather, all populations
      appeared to be independently regulated at carrying capacity, with a balanced
      exchange of dispersers among populations. These two species have suffered recent
      reductions in range, and they are ecologically similar to other species that have
      declined to extinction in inland Australia. It has been argued that part of the
      cause of the vulnerability of species like these is that they exhibit source-sink
      dynamics, and disturbance to source habitats can therefore cause large-scale
      population collapses. The results of our study argue against this interpretation.

PMID- 15583940
TI  - Bottom-up effects of nutrient availability on flower production, pollinator
      visitation, and seed output in a high-Andean shrub.
AB  - Soil nutrient availability directly enhances vegetative growth, flowering, and
      fruiting in alpine ecosystems. However, the impacts of nutrient addition on
      pollinator visitation, which could affect seed output indirectly, are unknown. In
      a nutrient addition experiment, we tested the hypothesis that seed output in the
      insect-pollinated, self-incompatible shrub, Chuquiraga oppositifolia (Asteraceae)
      of the Andes of central Chile, is enhanced by soil nitrogen (N) availability. We
      aimed to monitor total shrub floral display, size of flower heads (capitula),
      pollinator visitation patterns, and seed output during three growing seasons on
      control and N addition shrubs. N addition did not augment floral display, size of
      capitula, pollinator visitation, or seed output during the first growing season.
      Seed mass and viability were 25-40% lower in fertilised shrubs. During the second
      growing season only 33% of the N addition shrubs flowered compared to 71% of
      controls, and a significant (50%) enhancement in vegetative growth occurred in
      fertilised shrubs. During the third growing season, floral display in N addition
      shrubs was more than double that of controls, received more than twice the number
      of insect pollinator visits, and seed output was three- to four-fold higher
      compared to controls. A significant (50%) enhancement in vegetative growth again
      occurred in N addition shrubs. Results of this study strongly suggest that soil N
      availability produces strong positive bottom-up effects on the reproductive
      output of the alpine shrub C. oppositifolia. Despite taking considerably longer
      to be manifest in comparison to the previously reported top-down indirect
      negative effects of lizard predators in the same study system, our results
      suggest that both bottom-up and top-down forces are important in controlling the
      reproductive output of an alpine shrub.

PMID- 15583941
TI  - Thuja plicata exclusion in ectomycorrhiza-dominated forests: testing the role of
      inoculum potential of arbuscular mycorrhizal fungi.
AB  - The ability of trees dependent on arbuscular mycorrhizal (AM) fungi to establish
      in ectomycorrhizal forests is unknown. On northern Vancouver Island, Canada,
      there are sharp boundaries between mixed red cedar (Thuja plicata)-hemlock (Tsuga
      heterophylla) (CH) stands, and stands of hemlock and amabilis fir (Abies
      amabilis) (HA). We tested differences in AM colonization of red cedar between
      ectomycorrhiza-dominated (HA) stands and stands containing red cedar (CH), across
      a range of light levels. We used a soil bioassay approach to determine whether
      there was sufficient AM fungal inoculum in the HA tree stands to colonize red
      cedar seedlings. Seeds of hemlock and red cedar were sown in forest floor samples
      collected from the two types of forests, and shade treatments ranging from < 1 to
      53% of full sunlight were imposed. After 6 months, seedling survival and root and
      shoot biomass were quantified, and red cedar seedlings were sampled for AM fungal
      colonization. Hemlock survival and growth did not differ between soil types,
      suggesting there was no substrate-associated limitation to its establishment in
      either forest type. Red cedar colonization by AM fungi was significantly
      correlated with light levels in CH soils but arbuscular mycorrhizas were absent
      in roots of red cedar seedlings grown in HA soil. Red cedar survival and relative
      growth rate were significantly greater in the CH than in HA soil; higher growth
      was due primarily to greater shoot growth in CH soils at high light levels. The
      low soil inoculum potential for red cedar in ectomycorrhiza-dominated stands may
      account for the virtual exclusion of red cedar seedlings from these forests.

PMID- 15583942
TI  - Dynamics of demographically open mutualists: immigration, intraspecific
      competition, and predation impact goby populations.
AB  - Although it is now recognized that mutualistic species are common and can have
      stable populations, the forces controlling their persistence are poorly
      understood. To better understand the mechanisms that impact the stability of
      obligate mutualists, I conducted several field experiments within a sandy coral
      reef lagoon in Moorea, French Polynesia that manipulated densities of fish
      (gobies) that interact mutualistically with shrimp. Obligate, mutualistic
      partnerships of gobies and shrimp are common on Indo-Pacific coral reefs and have
      been shown previously to interact as follows: shrimp construct burrows in which
      both species reside, and gobies warn shrimp of predators through tactile
      communication. Augmentation of gobies by up to 100% above ambient densities
      within 9 m2 plots produced no change in overall density of gobies or shrimp
      because gobies competed intraspecifically for a limited number of shrimp burrows
      and smaller gobies were outcompeted by larger individuals. I used predators to
      assess the impact of goby removal on the stability of goby and shrimp
      populations. First, although surveys taken throughout the lagoon revealed no
      relationship between goby and predator densities, predators correlated negatively
      with the proportion of adult gobies and positively with the proportion of small
      gobies paired with large shrimp. Second, experimental augmentation of predators
      resulted in a dramatic reduction of adult gobies within predator-addition plots,
      but had no impact on overall densities as immigrants rapidly replaced the missing
      adult gobies. Furthermore, goby turnover resulted in an increase in the
      proportion of small gobies paired with large shrimp because body sizes of gobies
      and shrimp in a burrow were similar prior to predator introduction, and predators
      apparently had a greater impact on gobies than shrimp. The mechanisms that
      prevent expansion (intraspecific competition) and collapse (immigration) of goby
      shrimp populations likely contribute to local-scale stability of mutualistic
      populations in other terrestrial and aquatic environments.

PMID- 15583943
TI  - Effects of nutrient variability on the genetic-based resistance of Eucalyptus
      globulus to a mammalian herbivore and on plant defensive chemistry.
AB  - Plant resistance to herbivores can be influenced not only by the independent
      effects of plant genotype and environmental variation, but by interactions
      between the two. The main aim of this study was to assess the effects of
      environmental variability (nutrient treatment) on the known genetic-based
      expression of resistance and defensive chemistry of Eucalyptus globulus to
      browsing by the generalist mammalian herbivore Trichosurus vulpecula. In a
      captive feeding trial, we measured intake of seedlings from one relatively
      resistant (Blue Gum Hill) and one relatively susceptible (St Helens) population
      of E. globulus grown under two nutrient treatments (no fertiliser, plus
      fertiliser). There was a significant genotypexfertiliser interaction effect on
      intake of E. globulus foliage by T. vulpecula, and the predicted genetic-based
      resistance of the two populations was expressed only for the non-fertilised
      treatment. Expression of resistance largely reflected the combined and inverse
      effects of nitrogen and condensed tannin concentrations. The expression of plant
      secondary metabolite concentration differed between compounds, but in all cases
      the effects of plant genotype and fertiliser treatment were independent. The
      formylated phloroglucinol compounds differed significantly between genotypes but
      not between fertiliser treatments. In contrast, the effect of plant genotype on
      the expression of condensed tannins was weak but they were significantly reduced
      by fertiliser. Essential oils were influenced by both plant genotype and
      fertiliser treatment and were significantly higher in the fertilised seedlings
      than in the non-fertilised seedlings. This study highlights interactive effects
      of plant genotype and environment in influencing the phenotypic expression of
      resistance in a eucalypt species to a mammalian browser. It also demonstrates
      that this interactive effect is the net result of independent effects of genotype
      and environment on plant chemistry and finally, that different groups of
      compounds within a plant can respond very differently to variation in
      environmental conditions.

PMID- 15583944
TI  - Construction of a novel immunoassay for the relationship between anxiety and the
      development of a primary immune response to adrenal cortical hormone.
AB  - A novel potentiometric immunosensor for the detection of adrenal cortical
      hormones (ACH) has been developed by means of self-assembling immobilization of
      adrenal cortical hormone antibody (anti-ACH) on a gold electrode-modified gold
      nanoparticle (Au) and a thiol-containing sol-gel network. A cleaned gold
      electrode was first immersed in a (3-mercaptopropyl)-trimethoxysilane (MPS) sol
      gel solution to assemble a silica sol-gel monolayer, then the silane units were
      polymerized into a 2D sol-gel network (2D network) by dipping into aqueous NaOH.
      The second silane layer was formed by immersion back into the MPS solution
      overnight, and then the gold nanoparticles (nanogold) were chemisorbed onto the
      thiol groups of the second silane layer. Finally, anti-ACH was adsorbed onto the
      surface of the gold nanoparticles. The modified process was characterized by
      electrochemical impedance spectroscopy (EIS). The detection is based on the
      change in the potentiometric response before and after the antigen-antibody
      reaction. Using nanogold and 3-MPS as substrates, potentiometric detection at
      room temperature resulted in a pseudolinear detection range of about 22-1,000 ng
      mL(-1) with a detection limit of 5.2 ng mL(-1). Subsequently, several serum
      samples obtained from medical students with different anxiety extents were
      analyzed comparing with the ELISA method, and the results demonstrated that the
      immunoassay meets the demands of psychological analyses.

PMID- 15583945
TI  - Increased systolic daily ambulatory blood pressure in adult women born preterm.
AB  - We have studied 24-h ambulatory blood pressure and kidney function in three
      groups of adult women: (1) born full term but with birth weights below the 3rd
      percentile for gestational age (n =18), (2) born preterm before gestational week
      33 (median birth weight 1,250 g, range 950-2,040 g) (ex-preterm, n =14), and (3)
      those born full term with normal birth weights (comparison group n =17). We have
      previously published the results from the study. We recalculated the daily
      ambulatory blood pressure and redefined the time interval from 6:00-24:00 to 8:00
      20:00, since this better corresponds to daily active life. We found significantly
      increased mean daily systolic ambulatory blood pressure in the ex-preterm group.
      The result supports the suggestion that disturbance and/or disruption of the
      normal prenatal milieu seem to affect arterial blood pressure in adult life.

PMID- 15583946
TI  - A new mutation in two siblings with cystinosis presenting with Bartter syndrome.
AB  - Nephropathic cystinosis is a severe autosomal recessive inherited metabolic
      disease characterized by accumulation of free cystine in lysosomes. Cystinosis
      can lead to renal failure and multiorgan impairment. Only five cases of
      cystinosis with associated Bartter syndrome are reported in the literature, and
      no genetic evaluation has been reported. We describe two siblings with
      nephropathic cystinosis presenting with features of Bartter syndrome and their
      genetic pattern.

PMID- 15583947
TI  - Aminophylline as an adjunct diuretic for neonates--a case series.
AB  - Aminophylline is an adenosine receptor antagonist. Adult and paediatric studies
      have demonstrated a diuretic effect of aminophylline due to increased renal blood
      flow and the inhibition of solute reabsorption in various segments of the
      nephron. We report a case series of five infants with volume overload despite
      frusemide treatment. Aminophylline was successfully used as an adjunct diuretic
      with increased urine output and effective weight loss occurring in all five
      neonates following its introduction.

PMID- 15583948
TI  - Cerebral vasculitis and intracerebral hemorrhage in Henoch-Schonlein purpura
      treated with plasmapheresis.
AB  - Severe neurological complications in Henoch-Schonlein purpura (HSP) are rare. We
      report a 13-year-old girl with HSP receiving oral steroid therapy for HSP
      nephritis who presented with acute onset of headache, confusion, and loss of
      bilateral vision. However, immediate cranial computed tomography showed merely a
      small intracranial hematoma in the left occipital area, which was not consistent
      with her clinical manifestations. The subsequent magnetic resonance imaging of
      the brain demonstrated bilateral, multifocal abnormalities with features
      consistent with cerebral vasculitis. Therapeutic plasmapheresis was performed
      immediately and there was rapid clinical improvement. In conclusion, we propose
      that plasmapheresis is a reliable and effective therapy and may be considered as
      the first-line treatment in this critical condition to prevent massive
      intracerebral hemorrhagic complication of this immune complex-mediated cerebral
      vasculitis leading to irreversible neurological sequelae or mortality.

PMID- 15583949
TI  - Hypertension and the vanishing kidney.
AB  - The diagnostic role of retrograde pyelography in children with secondary
      hypertension has never been discussed in the literature. We report a child with
      severe hypertension, who apparently has a normal renin level and a solitary
      kidney by renal sonography and renal scan. Retrograde pyelography was able to
      identify the scarred renal mass. To our knowledge this is the first report to
      discuss the role of retrograde pyelography in a child with a solitary kidney and
      severe hypertension.

PMID- 15583950
TI  - Nutrition intervention improves outcomes in patients with cancer cachexia
      receiving chemotherapy--a pilot study.
AB  - GOALS OF THE WORK: The aim of this study was to examine the effect of nutrition
      intervention on outcomes of dietary intake, body composition, nutritional status,
      functional capacity and quality of life in patients with cancer cachexia
      receiving chemotherapy. PATIENTS AND METHODS: Patients received weekly
      counselling by a dietitian and were advised to consume a protein- and energy
      dense oral nutritional supplement with eicosapentaenoic acid for 8 weeks. The
      medical oncologist determined the chemotherapy protocol. Eight patients enrolled
      and seven completed the study. MAIN RESULTS: There were significant improvements
      in total protein intake (median change 0.3 g/kg per day, range -0.1 to 0.8 g/kg
      per day), total energy intake (median change 36 kJ/kg per day, range -2 to 82
      kJ/kg per day), total fibre intake (median change 6.3 g/day, range -3.4 to 20.1
      g/day), nutritional status (patient-generated subjective global assessment score,
      median change 9, range -5 to 17), Karnofsky performance status (median change 10,
      range 0-30) and quality of life (median change 16.7, range 0-33.3). There were
      clinically significant improvements in weight (median change 2.3 kg; range -2.7
      to 4.5 kg) and lean body mass (median change 4.4 kg, range -4.4 to 4.7 kg),
      although these were not statistically significant. Change in nutritional status
      was significantly associated with change in quality of life, change in Karnofsky
      performance status and change in lean body mass. CONCLUSIONS: Nutrition
      intervention together with chemotherapy improved outcomes in patients with
      pancreatic and non-small-cell lung cancer over 8 weeks. Supplement intake does
      not inhibit meal intake.

PMID- 15583951
TI  - Morphological changes of the ligamentum flavum as a cause of nerve root
      compression.
AB  - The ligamentum flavum is considered to be one of the important causes of
      radiculopathy in lumbar degenerative disease. Although there have been several
      reports anatomically examining the positional relationship between the ligamentum
      flavum and nerve root, there are few reports on ventral observation. The purpose
      of this study is to clarify the shape of the ligamentum flavum seen ventrally,
      and to obtain anatomic findings related to nerve root compression. The subjects
      were 18 adult embalmed cadavers, with an average age of 78 years at the time of
      death. The ventral shapes of the ligamentum flavum were observed. The
      relationships between the morphological change of the ligamentum flavum and nerve
      root compression or radiographic findings were statistically evaluated. Among the
      shapes of the ligamentum flavum, bulging of the ligament was most frequently
      observed. Proximal bulging indicates the type with the cranial portion bulging
      from the subarticular zone to the foraminal zone of the ligamentum flavum. In
      this type associated with a decrease in disc height, nerve root compression was
      frequently observed. Thus, we could more realistically grasp the relationship
      between bulging morphology of the ligamentum flavum and nerve root compression.

PMID- 15583952
TI  - Salivary cortisol and aggression in a population-based longitudinal study of
      adolescent males.
AB  - Chronic antisocial behaviour in youth has been associated with cortisol, a
      measure of stress reactivity. However, some studies have found low cortisol
      levels, while others have found elevated cortisol levels. The present study
      compared variously defined aggressive subgroups for differences in salivary
      cortisol. A population-based sample of boys was followed longitudinally from
      childhood to adolescence. Assessments of different forms of antisocial behaviour
      were obtained from various informants at several points in time, and cortisol was
      collected at age 13. Higher cortisol levels were found in boys with conduct
      disorder (CD) than in boys without CD. In addition, boys with an aggressive form
      of CD had higher cortisol levels than boys who showed a covert form of CD.
      Furthermore, reactive aggression was strongly correlated with elevated cortisol.
      Adolescent boys with chronic reactive aggression and those who scored high on
      aggressive CD symptoms seem to have a more active hypothalamic-pituitary-adrenal
      system.

PMID- 15583953
TI  - Negative association between catechol-O-methyltransferase (COMT) gene Val158Met
      polymorphism and persistent tardive dyskinesia in schizophrenia.
AB  - Chronic administration of typical antipsychotic agents, which mainly act on the
      dopamine receptors, implicates a role of dopamine system on the susceptibility of
      tardive dyskinesia (TD). In the present study, the association between a
      functional Val158Met polymorphism of Catechol-O-methyltransferase (COMT) gene and
      TD occurrence and TD severity was investigated in 299 Chinese schizophrenic
      patients with long-term antipsychotic treatment (TD: 166, non-TD: 133). After
      adjusting the effects of confounding factors, there was no significant
      association between COMT genotype and TD occurrence (p=0.367). Among TD patients,
      we found no significant correlation between COMT genotypes and the total scores
      of abnormal involuntary movement scale (AIMS) (p=0.629). We concluded that this
      COMT polymorphism might not play a major role in the susceptibility of TD nor on
      the severity of TD.

PMID- 15583954
TI  - Early stages (P100) of face perception in humans as measured with event-related
      potentials (ERPs).
AB  - According to current ERP literature, face specific activity is reflected by a
      negative component over the inferior occipito-temporal cortex between 140 and 180
      ms after stimulus onset (N170). A recently published study (Liu et al., 2002)
      using magnetoencephalography (MEG) clearly indicated that a face-selective
      component can be observed at 100 ms (M100) which is about 70 ms earlier than
      reported in most previous studies. Here we report these early differences at 107
      ms between the ERPs of faces and buildings over the occipito-temporal cortex
      using electroencephalography. To exclude contrast differences as the main factor
      for this P100 differences we replicated this study using pictures of faces and
      scrambled faces. Both studies indicated that face processing starts already at
      approximately 100 ms with an initial stage which can be measured not only with
      MEG but also with ERPs.

PMID- 15583955
TI  - Neuroprotective treatment with cerebrolysin in patients with acute stroke: a
      randomised controlled trial.
AB  - BACKGROUND AND PURPOSE: Cerebrolysin is a compound with neurotrophic and
      neuroprotective activity. It is produced by enzymatic breakdown of purified brain
      proteins and consists of low molecular weight peptides and amino acids. Cellular
      and animal models of cerebral ischaemia have shown that it is a potent
      neuroprotective agent. We explored the safety and preliminary outcome of
      Cerebrolysin treatment in patients with acute stroke. METHODS: Randomised,
      placebo-controlled, parallel group trial. Patients with acute stroke were
      randomised within 24 h of stroke onset to IV therapy with placebo or Cerebrolysin
      50 mL/day for 21 days. Both groups received concomitant treatment with ASA 250
      mg/day PO and pentoxifylline 300 mg/day IV. Clinical examinations were performed
      on days 1, 3, 7, 21 and 90 post baseline. Outcome measures were the Canadian
      Neurological Scale, the Barthel Index, the Clinical Global Impressions, the Mini
      Mental State Examination, and the Syndrome Short Test. Treatment emergent adverse
      events, lab tests, and vital signs were recorded to assess the safety of
      Cerebrolysin. RESULTS: 146 patients were enrolled in two groups: 78 Cerebrolysin
      and 68 placebo. At baseline, no significant group differences were observed.
      Patients in the Cerebrolysin group had no significant improvement in the CNS
      score, the Barthel Index and the Clinical Global Impressions when compared to the
      placebo group. A significant improvement of cognitive function of the patients on
      Cerebrolysin was observed in the Syndrome Short Test when compared to the placebo
      group. Cerebrolysin was well tolerated and safe. Adverse events occurred with a
      similar frequency in both groups. CONCLUSION: The results demonstrate that
      neurotrophic treatment with Cerebrolysin is safe and well tolerated by patients
      with acute stroke. The findings, despite the small sample size, also indicate a
      potential treatment effect of Cerebrolysin in acute stroke. Larger studies,
      however, are needed to confirm and extend these findings.

PMID- 15583956
TI  - Efficacy of budipine and placebo in untreated patients with Parkinson's disease.
AB  - Previous studies demonstrated the efficacy of budipine on motor symptoms of
      treated patients with Parkinson's disease (PD) with rating scales. However rating
      procedures may be subjective and variable. Therefore additional use of
      instrumental motor tests are helpful to reflect therapeutic benefits. Objective
      was to test the efficacy of 20 mg budipine (t.i.d.) in 51 previously untreated
      idiopathic PD patients in a monocenter, double-blind, placebo-controlled trial
      with a 2:1 randomisation over a three month interval. Budipine was not superior
      to placebo application. However a detailed analysis of rating results shows, that
      budipine but not placebo treated patients significantly improved. Budipine caused
      significant better outcomes of motor tests with execution of complex movements,
      but did not change results of tasks, which demand for simple motions. Placebo
      significantly improved dopamine sensitive motor test results. These outcomes may
      result from improved non dopaminergic neurotransmission due to budipine. Placebo
      caused better results of dopamine sensitive tests, since placebo may release
      endogenous dopamine.

PMID- 15583957
TI  - Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and
      cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells.
AB  - Ethanol-induced cell damage was investigated using human neuroblastomas SH-SY5Y
      cells, which can be differentiated by retinoic acid. With 100 mM or more of
      ethanol, cytotoxicity was significantly higher in undifferentiated cells than in
      differentiated cells. Thus, a severer effect of ethanol was observed in
      undifferentiated cells. In differentiated cells it was shown that the secreted
      amount of brain derived neurotrophic factor (BDNF) and the cyclic AMP responsive
      element binding protein (CREB) activity were significantly reduced by ethanol.
      These effects may be involved in ethanol-induced cell damage in differentiated
      cells. It was reported that neurotrophic factors have protective effects and that
      the hippocampus exclusively was damaged by ethanol. Since SH-SY5Y cell is a cell
      line (a neuronal cell model) and similar cytotoxic effect of ethanol was observed
      in both SH-SY5Y and primary culture neuronal cells, it will be favorable to use
      primary culture cells to test a protective effect of BDNF. Exogenous BDNF was
      shown to have a protective effect against ethanol-induced damage in primary
      culture neurons from rat hippocampi.

PMID- 15583958
TI  - Riluzole improves motor deficits and attenuates loss of striatal neurons in a
      sequential double lesion rat model of striatonigral degeneration (parkinson
      variant of multiple system atrophy).
AB  - We investigated neuroprotective effects of riluzole, an anti-glutamatergic agent
      that is FDA approved for disease-modifying therapy in amyotrophic lateral
      sclerosis (ALS), in an established double lesion rat model of striatonigral
      degeneration (SND), the neuropathological substrate of parkinsonism associated
      with MSA (MSA-P). Riluzole was administered prior to and consecutively for ten
      days following double lesion placement in the left-sided medial forebrain bundle
      and ipsilateral striatum. Assessment of motor behaviour using a flex field system
      showed a significant reduction of motor disturbance in animals with striatonigral
      lesions treated with riluzole compared to lesioned but untreated animals
      (P<0.001). DARPP-32 immunohistochemistry revealed a significant reduction of
      absolute striatal lesion volume in riluzole treated animals compared to lesioned
      but untreated animals (P<0.01). No significant difference in counts of nigral
      dopaminergic neurons was found in treated versus untreated double-lesioned
      animals. The results of our study indicate that riluzole mediates neuroprotective
      effects in the double lesion rat model of MSA-P. Whether riluzole also protects
      autonomic and cerebellar pathways that are frequently affected in MSA remains to
      be determined. Nonetheless, our study is the first to provide an experimental
      rationale for exploring possible neuroprotective effects of riluzole in MSA.

PMID- 15583959
TI  - Relationship between Alzheimer's disease clinical stage and Gq/11 in subcellular
      fractions of frontal cortex.
AB  - Alzheimer's disease (AD) is associated with impaired coupling of cell surface
      muscarinic cholinergic receptors to G proteins of the Gq/11 class in brain. This
      alteration may contribute to progression of cognitive impairment during the
      course of the disease. We hypothesized that increasing severity of cognitive
      impairment would be related to decreased levels of Gq/11 detected in key
      subcellular fractions made from postmortem brain tissue. In this study, we used
      Western blotting to determine the quantity of Gq/11alpha in P2, synaptic plasma
      membrane, cytoplasm, microsomal membrane, and lipid raft fractions prepared from
      superior frontal cortex gray matter of 25 patients with clinical AD confirmed by
      post-mortem examination. Multiple linear regression analysis that adjusted for
      age, sex, and education showed a linear relationship between frontal cortex
      synaptic plasma membrane Gq/11alpha levels and severity of cognitive impairment
      determined by Mini Mental State score measured proximate to death.

PMID- 15583960
TI  - Oxidative stress mechanisms and potential therapeutics in Alzheimer disease.
AB  - Oxidative damage of biological macromolecules is a hallmark of most
      neurodegenerative disorders such as Alzheimer, Parkinson and diffuse Lewy body
      diseases. Another important phenomenon involved in these disorders is the
      alteration of iron and copper homeostasis. Data from the literature support the
      involvement of metal homeostasis in mitochondrial dysfunction, protein
      alterations and nucleic acid damage which are relevant in brain function and
      consequently, in the development of neurodegenerative disorders. Although
      alterations in transition metal homeostasis, redox activity, and localization are
      well documented, it must be determined how alterations of specific copper- and
      iron-containing metalloenzymes are also involved in Alzheimer disease. The
      clarification of these phenomena can open a new window for understanding the
      mechanisms underlying neurodegeneration and, consequently, for the development of
      new therapeutic strategies such as gene therapy and new pharmaceutical
      formulations with antioxidant and chelating properties.

PMID- 15583961
TI  - Hyperphosphorylation-induced self assembly of murine tau: a comparison with human
      tau.
AB  - Alzheimer's disease-like neurofibrillary pathology is neither seen in rodents nor
      in transgenic animals expressing the disease causing mutant human APP or mutant
      human presenilins. Whether the absence of this pathology is due to inability of
      the murine tau to self assemble into filaments or due to some other factors is
      not understood. In this study, we compared recombinant murine and human taus in
      their ability to form filaments by AD-like hyperphosphorylation in vitro. Human
      and murine taus, 0N4R, were generated as recombinant proteins and phosphorylated
      with rat brain extract as a source of protein kinases. We found that murine tau
      could be hyperphosphorylated to similar stoichiometry and manner as human tau.
      Upon hyperphosphorylation, murine tau was able to self polymerize into bundles of
      paired helical filament- and straight filament-like morphology. The filaments
      obtained from self assembly of murine tau closely resembled those formed from
      identically treated human tau. Moreover, like human tau, 60-70% of murine tau
      aggregated on hyperphosphorylation.

PMID- 15583962
TI  - Intra-parenchymal injection of tumor necrosis factor-alpha and interleukin 1-beta
      produces dopamine neuron loss in the rat.
AB  - Inflammatory processes are thought to underlie the dopamine (DA) neuron loss seen
      in Parkinson's disease (PD). However, it is not known if the inflammation
      precedes that loss, or is a consequence of it. We injected tumor necrosis factor
      alpha (TNFalpha) and interleukin 1 beta (IL-1beta) into the median forebrain
      bundle to determine if these pro-inflammatory cytokines could induce DA neuron
      loss in the substantia nigra (SN) by themselves. The magnitude of the DA cell
      loss as well as the decreases in striatal DA, were both dose and time to
      sacrifice dependent. Injecting both cytokines together produced greater cell
      losses and DA reductions than that seen when the cytokines were injected alone.
      The DA neuron loss seen was more pronounced in the lateral nigra and its ventral
      tier and similar to that seen when other toxins are injected. These data suggest
      that TNFalpha and IL-1beta can induce DA neuron loss by themselves and could
      produce DA neuron loss independent of other inflammatory events.

PMID- 15583963
TI  - Morphinome--proteome of the nervous system after morphine treatment.
AB  - Proteome is a natural consequence of the post-genome era when the HUGO project
      (Human Genome Organization) has almost been completed. Here, a specifically aimed
      proteome in drug dependence--morphinome, is described, including tasks,
      strategies and pitfalls of the methodology.

PMID- 15583964
TI  - Heme-copper/dioxygen adduct formation relevant to cytochrome c oxidase:
      spectroscopic characterization of [(6L)FeIII-(O2(2-))-CuII]+.
AB  - In the further development and understanding of heme-copper dioxygen reactivity
      relevant to cytochrome c oxidase O(2)-reduction chemistry, we describe a high
      spin, five-coordinate dioxygen (peroxo) adduct of an iron(II)-copper(I) complex,
      [((6)L)Fe(II)Cu(I)](BArF(20)) (1), where (6)L is a tetraarylporphyrinate with a
      tethered tris(2-pyridylmethyl)amine chelate for copper. Reaction of 1 with O(2)
      in MeCN affords a remarkably stable [t(1/2) (rt; MeCN) approximately 60 min]
      adduct, [((6)L)Fe(III)-(O(2) (2-))-Cu(II)](+) (2) [EPR silent; lambda(max)=418
      (Soret), 561 nm], formulated as a peroxo complex based on manometry (1:O(2)=1:1;
      spectrophotometric titration, -40 degrees C, MeCN), mass spectrometry {MALDI-TOF
      MS: (16)O(2), m/z 1191 ([((6)L)Fe(III)-((16)O(2) (2-))-Cu(II)](+)); (18)O(2), m/z
      1195}, and resonance Raman spectroscopy (nu((O-O))=788 cm(-1);
      Delta(16)O(2)/(18)O(2)=44 cm(-1); Delta(16)O(2)/(16/18)O(2)=22 cm(-1)). (1)H and
      (2)H NMR spectroscopy (-40 degrees C, MeCN) reveals that 2 is the first heme
      copper peroxo complex which is high-spin, with downfield-shifted pyrrole
      resonances (delta(pyrrole)=75 ppm, s, br) and upfield shifted peaks at delta= 
      22, -35, and -40 ppm, similar to the pattern observed for the mu-oxo complex
      [((6)L)Fe(III)-O-Cu(II)](BAr(F)) (3) (known S=2 system, antiferromagnetically
      coupled high-spin Fe(III) and Cu(II)). The corresponding magnetic moment
      measurement (Evans method, CD(3)CN, -40 degrees C) also confirms the S=2 spin
      state, with mu(B)=4.9. Structural insights were obtained from X-ray absorption
      spectroscopy, showing Fe-O (1.83 A) and Cu-O (1.882 A) bonds, and an Fe...Cu
      distance of 3.35(2) A, suggestive of a mu-1,2-peroxo ligand present in 2. The
      reaction of 2 with cobaltocene gives 3, differing from the observed full
      reduction seen with other heme-Cu peroxo complexes. Finally, thermal
      decomposition of 2 yields 3, with concomitant release of 0.5 mol O(2) per mol 2,
      as confirmed quantitatively by an alkaline pyrogallol dioxygen scavenging
      solution.

PMID- 15583965
TI  - Cloning, expression, and characterization of a highly thermostable family 18
      chitinase from Rhodothermus marinus.
AB  - A family 18 chitinase gene chiA from the thermophile Rhodothermus marinus was
      cloned and expressed in Escherichia coli. The gene consisted of an open reading
      frame of 1,131 nucleotides encoding a protein of 377 amino acids with a
      calculated molecular weight of 42,341 Da. The deduced ChiA was a non-modular
      enzyme with one unique glycoside hydrolase family 18 catalytic domain. The
      catalytic domain exhibited 43% amino acid identity with Bacillus circulans
      chitinase C. Due to poor expression of ChiA, a signal peptide-lacking mutant,
      chiADeltasp, was designed and used subsequently. The optimal temperature and pH
      for chitinase activity of both ChiA and ChiADeltasp were 70 degrees C and 4.5-5,
      respectively. The enzyme maintained 100% activity after 16 h incubation at 70
      degrees C, with half-lives of 3 h at 90 degrees C and 45 min at 95 degrees C.
      Results of activity measurements with chromogenic substrates, thin-layer
      chromatography, and viscosity measurements demonstrated that the chitinase is an
      endoacting enzyme releasing chitobiose as a major end product, although it acted
      as an exochitobiohydrolase with chitin oligomers shorter than five residues. The
      enzyme was fully inhibited by 5 mM HgCl2, but excess ethylenediamine tetraacetic
      acid relieved completely the inhibition. The enzyme hydrolyzed 73% deacetylated
      chitosan, offering an attractive alternative for enzymatic production of
      chitooligosaccharides at high temperature and low pH. Our results show that the
      R. marinus chitinase is the most thermostable family 18 chitinase isolated from
      Bacteria so far.

PMID- 15583966
TI  - [Osteoblast reaction on SLA and microgrooved implant surfaces].
AB  - The osseointegration process of dental implants depends on the tissue reaction at
      the tissue-implant interface. Osteoblasts are the main cells responsible for the
      regulation of osteoinduction. The manner and kinetics of the tissue reaction
      crucially depend on the interaction between osteoblasts and the morphology of the
      implant surface. The aim of this study was to investigate osteoblast behaviour on
      different implant surfaces (smooth, microgrooved, SLA) under standardized
      conditions. For this in vitro investigation we used primary bovine osteoblasts.
      Attachment kinetics, proliferation rate and synthesis of bone-associated proteins
      were used as parameters for cell reaction. The results demonstrate that both
      attachment and adhesion strength of the primary cell surface interaction was
      higher on the microgrooved surfaces than on SLA surfaces. The proliferation rate
      of cells and the synthesis of bone-specific proteins were higher on microgrooved
      surfaces in contrast to SLA surfaces. Ultrastructural analysis revealed
      phenotypic osteoblast-like cells on smooth and microgrooved surfaces, whereas
      cells on SLA surfaces showed a more fibroblastic appearance. This study
      demonstrates that the morphology of the implant surface determined the subsequent
      osteoblast reaction. An optimal cell reaction was found at surfaces which are
      smooth in the microenvironment of osteoblasts.

PMID- 15583967
TI  - Titanium coating of a polypropylene mesh for hernia repair: effect on
      biocompatibilty.
AB  - Titanium and its alloys are used worldwide in surgery. The favorable
      characteristics that make this material desirable for implantation are corrosion
      resistance and biocompatibility. Concerning hernia repair, a mesh modification
      has been developed using titanium layering of a polypropylene mesh implant, which
      is said to lead to an improved biocompatibility compared to commercially
      available mesh materials. To analyze the pure effect of titanium coating, two
      different mesh structures were studied using a standardized animal model. The
      titanium-coated monofilamentous, large porous, and lightweight mesh made of
      polypropylene and coated with titanium (PP+T) was compared to a pure
      polypropylene mesh manufactured with a similar structure and amount of material
      serving as a control (PP). In Sprague-Dawley rats, mesh samples were placed in a
      subcutaneuous position. Then 56, 84, and 182 days after mesh implantation, three
      animals from each group were sacrificed for morphological observations (amount of
      inflammatory and connective tissue formation, percentages of proliferating and
      apoptotic cells, percentage of macrophages). Both mesh modifications investigated
      showed an overall good biocompatibility. Macroscopic clinical observation after
      implantation of up to 182 days was uneventful. The tissue response to the PP as
      well as to the PP+T mesh was characterized by a moderate inflammatory tissue
      reaction limited to the perifilamentary region as is known for low weight, large
      porous, and monofilamentous mesh structures. No significant improvement of
      biocompatibility was found when analyzing the effect of titanium coating compared
      to the pure polypropylene mesh structure.

PMID- 15583968
TI  - Laparoscopic management of an internal double omental hernia: a rare cause of
      intestinal obstruction.
AB  - INTRODUCTION: Internal hernia is a very rare cause of intestinal obstruction (0.2
      0.9% of cases), associated with 45% mortality. A review of the literature
      revealed just eight reported cases of double omental hernia since 1950 of which
      our patient is the first case successfully treated laparoscopically. CASE
      PRESENTATION: We report on a 29-year-old man who presented with signs and
      symptoms of intestinal obstruction. The patient underwent emergent exploratory
      laparoscopy. This revealed herniation of a 20-cm jejunal loop through the
      gastrocolic ligament and reemergence through a defect in the gastrohepatic
      ligament. The strangulated loop was reduced with slight traction, and the defect
      was repaired. The patient was discharged from hospital in just 5 days' time, and
      after 6 months of follow-up, the general condition of the patient was normal.
      CONCLUSIONS: Laparoscopy is a good technique with minimal complications compared
      with laparotomy. As many cases are missed due to nonspecific signs and symptoms,
      an urgent laparoscopy or laparotomy is highly recommended in such a situation.

PMID- 15583969
TI  - Incarcerated transdiaphragmatic intercostal hernia preceded by Chilaiditi's
      syndrome.
AB  - Transdiaphragmatic hernia most often develops after blunt or penetrating
      thoracoabdominal trauma. We report on the case of a 73-year-old man who underwent
      emergency ileocoecal resection for an incarcerated transdiaphragmatic intercostal
      hernia. The patient's history included both a lumbotomy for right nephrectomy and
      Chilaiditi's syndrome. The literature regarding both transdiaphragmatic
      intercostal herniation and Chilaiditi's syndrome is reviewed in relation to the
      presented case.

PMID- 15583970
TI  - OPG/RANKL system imbalance in a case of hepatitis C-associated osteosclerosis:
      the pathogenetic key?
AB  - Hepatitis C-associated osteosclerosis (HCAO) is an impressive example of acquired
      diffuse osteosclerosis in adults, recently described in ten patients infected
      with hepatitis C virus (HCV). Its hallmark is a painful and generalized increase
      of bone mass. Bone biopsies show enhanced accretion rate, usually without
      histological abnormalities. The HCAO pathogenesis is hitherto unknown. HCV might
      induce a slow bone cell infection and the production of bone growth factors, such
      as insulin-like growth factors. Recently, receptor activator of nuclear factor
      kappaB (RANK), its ligand (RANKL), and soluble decoy receptor osteoprotegerin
      (OPG) have been identified as a pivotal cytokine system in the bone remodeling
      control. We describe the 11th case of HCAO. Notably, the patient's bone biopsy
      showed the presence of a high number of OPG-positive osteoblasts, a slight
      increase of RANKL-positive stromal cells, and a dramatic reduction of the
      osteoclasts. Moreover, OPG serum levels were increased. These findings reported
      here for the first time are consistent with a pathogenetic role of the OPG/RANKL
      system imbalance in HCAO.

PMID- 15583971
TI  - Trace elements and some extracellular antioxidant proteins levels in serum of
      patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic progressive autoimmune disorder
      with a wide spectrum of clinical and immunological abnormalities. In this study,
      we aimed to investigate the levels of serum zinc (Zn), copper (Cu), magnesium
      (Mg), manganese (Mn), iron (Fe), ceruloplasmin (Cp), transferrin (Trf), and
      albumin (Alb) in SLE and whether it is related to the severity of the clinical
      condition of this chronic disease. Cp and Cu levels were higher, while Trf, Alb,
      Zn, Mg, Mn, and Fe levels were lower in serum of patients with SLE (n = 27)
      compared with healthy controls (n = 20). The mechanisms by which these
      alterations occur in certain inflammatory conditions need to be elucidated. It is
      also obscure whether these alterations are a cause or a consequence of the
      inflammation. As a conclusion, alterations in the levels of the parameters in SLE
      may not be a reason for, but in fact a consequence of the disease itself.

PMID- 15583972
TI  - Influence of ambient atmosphere on charge transport in polycrystalline thin films
      of three simple aromatic hydrocarbons.
AB  - Drift mobility of charge carriers in p-terphenyl, p-quaterphenyl and tetracene
      polycrystalline thin films was measured using the classical time-of-flight
      method. The measurements were carried out both in the atmosphere and in vacuum of
      the order of 10( - 3) Torr. The mobility measured in the atmosphere is of the
      order of 10(-4)cm2 V(-1) s(-1) and turns out to be about 1 order of magnitude
      higher than that measured in vacuum. It is suggested that the hopping transport
      of charge dominates in the structures investigated. The increase in the mobility
      for the measurements in the atmosphere probably results from the additional
      localized states due to water and other atmosphere molecules.

PMID- 15583973
TI  - The mobility of the amorphous phase in polyethylene as a determining factor for
      slow crack growth.
AB  - Polyethylene (PE) pipes generally exhibit a limited lifetime, which is
      considerably shorter than their chemical degradation period. Slow crack growth
      failure occurs when pipes are used in long-distance water or gas distribution
      though being exposed to a pressure lower than the corresponding yield stress.
      This slow crack growth failure is characterized by localized craze growth and
      craze fibril rupture. In the literature, the lifetime of PE pipes is often
      considered as being determined by the density of tie chains connecting adjacent
      crystalline lamellae. But this consideration cannot explain the excellent
      durability of the recent bimodal grade PE for pipe application. We show in this
      paper the importance of the craze fibril length as the determining factor for the
      pipe lifetime. The conclusions are drawn from stress analysis. It is found that
      longer craze fibrils sustain lower stress and are deformed to a lesser degree.
      The mobility of the amorphous phase is found to control the amount of material
      that can be "sucked" in by the craze fibrils and thus the length of the craze
      fibrils. The mobility of the amorphous phase can be monitored by dynamic
      mechanical analysis measurements. Excellent agreement between the mobility thus
      derived and lifetimes of PE materials as derived from FNCT (full notch creep
      test) is given, thus providing an effective means to estimate the lifetime of PE
      pipes by considering well-defined physical properties.

PMID- 15583974
TI  - Interspecific difference in the photosynthesis-nitrogen relationship: patterns,
      physiological causes, and ecological importance.
AB  - The photosynthesis-nitrogen relationship is significantly different among
      species. Photosynthetic capacity per unit leaf nitrogen, termed as photosynthetic
      nitrogen-use efficiency (PNUE), has been considered an important leaf trait to
      characterise species in relation to their leaf economics, physiology, and
      strategy. In this review, I discuss (1) relations between PNUE and species
      ecology, (2) physiological causes and (3) ecological implications of the
      interspecific difference in PNUE. Species with a high PNUE tend to have high
      growth rates and occur in disturbed or high productivity habitats, while those
      with a low PNUE occur in stressful or low productivity habitats. PNUE is an
      important leaf trait that correlates with other leaf traits, such as leaf mass
      per area (LMA) and leaf life span, irrespective of life form, phylogeny, and
      biomes. Various factors are involved in the interspecific difference. In
      particular, nitrogen allocation within leaves and the mesophyll conductance for
      CO(2) diffusion are important. To produce tough leaves, plants need to allocate
      more biomass and nitrogen to make thick cell walls, leading to a reduction in the
      mesophyll conductance and in nitrogen allocation to the photosynthetic apparatus.
      Allocation of biomass and nitrogen to cell walls may cause the negative
      relationship between PNUE and LMA. Since plants cannot maximise both PNUE and
      leaf toughness, there is a trade-off between photosynthesis and persistence,
      which enables the existence of species with various leaf characteristics on the
      earth.

PMID- 15583975
TI  - Accuracy of 3D MR microscopy for trabecular bone assessment: a comparative study
      on calcaneus samples using 3D synchrotron radiation microtomography.
AB  - Magnetic resonance (MR) imaging is attractive for a noninvasive and radiation
      free assessment of in vivo trabecular bone architecture. However the quantitative
      evaluation of architectural parameters could be biased by the limited sensitivity
      of MR. The aim of this study was to determine the accuracy of trabecular bone
      architectural parameters obtained from 3D high-resolution MR images, by
      comparison to reference images obtained by high-resolution X-ray microtomography
      using synchrotron radiation, from 29 samples of human calcaneus. MR images were
      obtained with a 66 microm x 66 microm x 66 microm voxel size, using a 8.5 T MR
      microscope. Microtomography images were acquired with a 10 microm x 10 microm x
      10 mum voxel size, from the same samples. 3D architectural parameters
      characterizing the morphometry, topology, anisotropy, and orientation were
      computed from both modalities and carefully compared. To avoid errors, an
      identical region of interest was selected in the two corresponding images, and
      the same algorithms were run at identical spatial resolution. Our results
      establish that network connectivity, orientation and anisotropy are reliable from
      the MR data. The bone volume fraction, and morphometric parameters measured from
      the MR data, were found to be biased with respect to their values from the
      microtomography data, although there was a significant correlation between the
      two modalities.

PMID- 15583976
TI  - Assessment of the preferred scout sagittal orientation for temporal lobe imaging
      with magnetic resonance.
AB  - Oblique magnetic resonance imaging of the temporal lobe (tilted orientation)
      requires a stable reference line with minimum variability. In the clinical
      setting, where several observers carry out examination of the patients, there is
      a need to assure minimum inter-observer variability, in order to obtain
      comparable tilted anatomical planes. This is particularly relevant when
      performing quantitative imaging (qMRI) of the hippocampus, amygdala and para
      hippocampal cortices. In this study, eight experienced observers tested the
      stability of four sagittal reference lines by manually tracing the posterior
      commissure-obex (PC-OB) line, the line tangential to the anterior surface of the
      pons at its most convex point and the lines orthogonal to the main axis of both
      hippocampi, in ten exams of healthy subjects. The stability of the tracing was
      assessed by comparing the inter-observer variability expressed by the variances
      of the measurements. The observers' performance was assessed by comparing the
      precision of the tracing for each line. We tested the results statistically using
      Bartlett's test (analysis of the variances of the four lines) followed by Fischer
      Snedecor (in order to compare the two lines that had the smallest variance). The
      PC-OB line and the line tangential to the anterior surface of the pons had
      smaller inter-observer variances than the orthogonal lines (p < 0.01). In
      addition, the variance of the PC-OB line was smaller than that of the line
      tangential to the pons (p < 0.01). There were no significant intra-observer
      differences in the precision of tracing of any of the lines. We show
      quantitatively that the PC-OB line is the scout reference that yields the
      smallest inter-observer variance. Thus, this line should be preferred to improve
      the reproducibility of temporal lobe imaging while performing tilted coronal and
      axial sequences, to make quantitative assessments of the hippocampus, amygdala
      and para-hippocampal cortices.

PMID- 15583977
TI  - [Gly374Arg mutation in Fgfr3 causes achondroplasia in mice].
AB  - OBJECTIVE: To establish the mouse model of Gly374Arg mutation in fibroblast
      growth factor receptor 3(Fgfr3) and to analyze the phenotype of the mutant mice.
      METHODS: The double PCR was used to introduce Gly374Arg point mutation into mouse
      Fgfr3. The electroporation of embryonic stem(ES) cells was carried out with
      targeting vector. The targeted ES cells were screened by Positive-Negative
      Selection of G418 and Ganciclovir, and Southern blot. The correct targeted ES
      cells were microinjected into blastula. Finally, mutant mice were obtained by
      crossing between EIIa-Cre transgenic mice and mice carrying recombined mutant
      Fgfr3 allele. The mice were genotyped by PCR, and phenotype was observed by
      skeleton staining, histology, etc. RESULTS: Fgfr3-Gly374Arg mutant mice exhibited
      small size, short tail, macrocephaly and had dome-shaped heads, the epiphyseal
      growth plates of mutant mice were narrower, and the hypertrophic chondrocyte zone
      was also obviously decreased. Meanwhile, the majority of female mice were
      infertile, and the uterus, ovary and mammal gland in mutant female mice were also
      smaller and underdeveloped. CONCLUSION: The model of Fgfr3-Gly374Arg mutation
      causing achondroplasia in mice has been established successfully.

PMID- 15583978
TI  - [Molecular cloning and characterization analysis of HPESCRG1, a novel gene
      expressed specifically in human embryonic stem cell].
AB  - OBJECTIVE: To clone a novel gene expressed specifically in human embryonic stem
      cell and to analyze its characteristics. METHODS: Based on an expression sequence
      tags(EST) CF948547 which expressed specifically in human embryonic stem cell, the
      full-length cDNA sequence of a novel gene was cloned by using bioinformatic and
      molecular biological technique. Its expression profile was analyzed by reverse
      transcription-polymerase chain reaction(RT-PCR), and subcellular location was
      determined by enhanced green fluorescent protein (EGFP) eukaryotic expression
      system. RESULTS: A novel gene HPESCRG1(homo sapiens pluripotent embryonic stem
      cell-related gene) was cloned successfully. Its GenBank accession number was
      AY283672. Its cDNA length was 1395 bp. It comprised 9 exons and 8 introns, and
      its opening reading frame was 250-1146 bp. Its chromosomal mapping was located in
      3q13.13, and the putative protein contained 297 amino acids. The theoretical
      molecular weight of the putative protein was 33 784 and the isoelectric point was
      9.35. The protein primary structure of this gene contained a SAP motif and it was
      subcellularly located in nuclei. Expression analysis showed that this gene was
      expressed specifically in human ES cells, but not expressed in the adult human
      tissues, the multiple tissues of embryo aborted in over 5 months' pregnancy, the
      differentiated cells of HESC-1, and the human mesenchymal stem cells (hMSCs) and
      human embryonic fibrocytes (hEFCs). CONCLUSION: HPESCRG1 was found to be a novel
      gene expressed specifically in human ES cell, which might be related to self
      renewal of human ES cell and maintaining its undifferentiated state.

PMID- 15583979
TI  - [Cloning, ligation and expression of the variable region genes of the monoclonal
      antibody against human HnRNPA2/B1].
AB  - OBJECTIVE: To clone the variable region genes of the monoclonal antibody (McAb)
      against human heterogeneous nuclear ribonucleoprotein A2/B1 (HnRNPA2/B1), ligate
      them to assemble single chain Fv (ScFv) gene and express in Escherichia coli.
      METHODS: The specificity of the anti-HnRNPA2/B1 McAb 3E8 to synthetic HnRNPA2/B1
      peptide, HnRNPA2/B1 protein in lung cancer cells were examined by dot
      immunobinding assay, Western blot and immunohistochemistry. The variable region
      genes of heavy chain (VH) and light chain (VL) were amplified from hybridoma cell
      by reverse transcription-polymerase chain reaction(RT-PCR), and then were linked
      by a linker peptide using SOE-PCR (splicing by overlap extension-PCR) to
      construct recombination ScFv gene. The latter was cloned into the expression
      vector pET28 (a+) and expressed in E coli BL21. The expressed product was
      identified by SDS-PAGE and competitive ELISA inhibition test. RESULTS: It was
      shown that the McAb combined specifically with synthetic HnRNPA2/B1 peptide and
      HnRNPA2/B1 protein in three lung cancer cells. The cloned VH gene and VL gene
      were 345 bp and 309 bp respectively and were linked successfully to obtain ScFv
      gene. The ScFv protein was expressed in the form of inclusion body, with
      molecular weight of 28,000 and immunoreactivity to HnRNPA2/B1. CONCLUSION: VH
      gene, VL gene and ScFv gene of anti-HnRNPA2/B1 antibody were cloned, constructed
      and functionally expressed in E coli. These results provide the experimental
      basis for elucidating the role of HnRNPA2/B1 in lung cancer.

PMID- 15583980
TI  - [Study on EcoR I fragment polymorphism of the subtelomeric domains within 4q35
      and 10q26 with pulsed field gel electrophoresis in the Chinese population].
AB  - OBJECTIVE: To elucidate the structural polymorphism of EcoR I fragment within
      chromosomes 4q35 and 10q26 in the Chinese population and investigate the
      relationship of plasticity, translocation and somatic mosaicism in these domains
      with deletion of D4Z4 repeated units. METHODS: One hundred and ten unrelated
      healthy individuals from a random Chinese population were investigated. The
      genomic DNA was extracted from peripheral blood lymphocytes according to the
      specific procedure designed to minimize DNA shearing, then digested with EcoR I
      or double digested with EcoR I and Bln I. The cleaved DNA was separated by pulsed
      field gel electrophoresis (PFGE) and Southern blotted with the probe p13E-11. The
      sizes of EcoR I fragments were calculated by "curve fitting" according to the
      MidRange PFG marker and the alleles were assigned to their respective chromosomes
      based on their Bln I sensitivity. Data were analyzed using a commercially
      available statistical package (Version 11.0 SPSS). RESULTS: Seventy-seven point
      three per cent (85/110) of the unrelated healthy individuals displayed a standard
      configuration distribution. The mean and median of 4q35 repeat arrays are (87.9+/
      3.3) kb and 78.5 kb respectively, whereas the mean and median of 10q26 homologous
      arrays are (90.1+/-4.1) kb and 73.0 kb. Repeat size distributions between both of
      them were of no significance according to the t test (P>0.05). 19.1% (21/110) of
      the individuals displayed a translocation repeat array configuration on
      chromosomes 4 and 10. No significant difference was detected between 4q-->10q
      translocation and 10q-->4q translocation according to Chisquare test (Chi2
      test=0.053, P>0.05). Somatic mosaicism was observed in 3.6% (4/110) of the
      subjects and less than 35 kb 10-type array was found in 14.5% (16/110) of the
      individuals. CONCLUSION: The structural polymorphism and dynamic behaviors of
      EcoR I fragments within 4q35 and 10q26 were demonstrated in this study using
      PFGE. The occurrence of frequent translocations and somatic mosaicism between
      4q35 and 10q26 subtelomeric domains in the Chinese population further confirmed
      that mitotic interchromosomal gene conversion or translocation might be a major
      mechanism relating to the deletion of D4Z4 units.

PMID- 15583981
TI  - [Inhibition of tumor growth and metastasis via local administration of
      recombinant human endostatin adenovirus].
AB  - OBJECTIVE: The growth and metastasis of solid tumors are dependent on
      angiogenesis. Endostatin, the C-terminal proteolytic fragment of collagen XVIII,
      is a potent endogenous angiogenesis inhibitor. The authors designed a topical
      antiangiogenic gene therapy with recombinant human endostatin adenovirus (Ad
      hEndo) and assessed its effects on the inhibition of angiogenesis in vitro, and
      tumor growth and metastasis in vivo. METHODS: Malignant cells (A549) were
      infected with Ad-hEndo. The expression of recombinant protein and the inhibition
      of cultured human umbilical vein endothelial were investigated. Immunodeficient
      A549 nude mice were treated with intratumoral injection of Ad-hEndo, the empty
      vector Ad-control or saline (NS). The dose-response, side effects, and serum
      concentration of endostatin were observed. RESULTS: Recombinant endostatin
      protein was detected in the infected tumor cells with different MOI Ad-hEndo and
      its inhibitory effect on endothelial cells growth was shown. In animal study, the
      volume of tumor and the number of pulmonary metastatic lesions in the Ad-hEndo
      treatment group were significantly smaller than those in the control groups
      (P<0.05). CONCLUSION: The present findings provide evidence of the anti-tumor
      effects of the endostatin and may be important for the further use of it in
      topical antiangiogenic gene therapy of cancer.

PMID- 15583982
TI  - [Two novel mutations in fibrillin-1 gene of Marfan syndrome].
AB  - OBJECTIVE: To detect novel mutations in the fibrillin-1(FBN1) gene by screening
      the gene from 9 patients with Marfan syndrome (MFS). METHODS: Denaturing high
      performance liquid chromatography (DHPLC) was used to screen for FBN1 mutation
      exon by exon. The DNA amplification fragments of which the DHPLC elution profiles
      showed difference in comparison with the corresponding normal elution profile
      were sequenced to identify the position and nature of mutation. The detected
      mutations were further proved by allele specific PCR or restriction fragment
      length polymorphism. RESULTS: Two novel FBN1 gene mutations were found and
      identified in two Marfan patients respectively, one of which was a small
      insertion in exon 34 at nucleotide 4307-4308 (4307insTCGT) and the other a
      missense mutation in exon 43 at nucleotide 5309 (5309G>A). CONCLUSION: The
      findings suggested that the frameshift mutation (4307insTCGT) and point mutation
      (5309G>A) caused the corresponding patients to have MFS.

PMID- 15583983
TI  - [The mutation V781I in SCN4A gene exists in Chinese patients with normokalemic
      periodic paralysis].
AB  - OBJECTIVE: In this report are reviewed two unrelated patients with typical
      normokalemic periodic paralysis (normoKPP) features and the results of screening
      the SCN4A gene for the disease-related mutation. METHODS: Two sporadic cases with
      normoKPP were screened for previously known mutations in SCN4A gene (T704M,
      A1156T, M1360V, I1495F, M1592V) that lead to hyperKPP; denaturing high
      performance liquid chromatography (DHPLC) was used. Then the rest exons of SCN4A
      gene were screened by DHPLC, and sequence analysis was performed on those with
      DHPLC chromatogram variation when compared with unaffected control. RESULTS: Two
      cases and one patient's father were detected with V781I, which was proved to be a
      singular missense mutation in SCN4A gene. CONCLUSION: The mutation V781I exists
      in Chinese patients with normoKPP and may be responsible for normoKPP.

PMID- 15583984
TI  - [Mutation analysis of keratin 9 gene in a pedigree with epidermolytic
      palmoplantar keratoderma].
AB  - OBJECTIVE: To identify mutations of keratin 9 (KRT9) gene in a big Chinese family
      with epidermolytic palmoplantar keratoderma(EPPK) combined with knuckle-pad-like
      lesions and nail lesions. METHODS: Genomic DNA from peripheral blood of all
      available members in this family and 50 unrelated healthy individuals was used
      for amplification of the whole coding sequence and the intron-exon boundaries of
      KRT9 gene by PCR; The mutation was detected by direct sequence analysis and
      identified by restriction endonuclease Dde I. RESULTS: A mutation of AAT>AGT at
      codon 160 (N160S) was found in all patients but not in unaffected family members
      and 50 controls. CONCLUSION: The mutation of AAT>AGT at codon 160 (N160S) is the
      disease-causing mutation in this Chinese pedigree with EPPK.

PMID- 15583985
TI  - [Studies on the genetic pathogenesis of myasthenia gravis caused by CTLA-4 gene
      polymorphism].
AB  - OBJECTIVE: To study the genetic pathogenesis of myasthenia gravis (MG) caused by
      cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphisms and
      regulation function of transcription factor. METHODS: ELISA assay was used to
      determine the expression level of serum sCTLA-4 in MG. Four single nucleotide
      polymorphisms (SNPs) of CTLA-4 at exon 1 +49, promoter -318, -1661, -1772 were
      analyzed by restriction fragment length polymorphism (RFLP). Transcription factor
      nuclear factor 1(NF-1) and c/EBPbeta binding site were confirmed by chromatin
      immunoprecipitation(CHIP) assay. RESULTS: It was found that the frequencies of
      the GG+49 genotype and G+49 allele are higher in MG patients with thymoma than
      those in patients of thymic hyperplasia and normal thymus subgroups. T/C-318 is
      not correlated with MG. The frequency of CT-1772 genotype is significantly higher
      in MG patients, especially in MG patients with thymoma, when compared with that
      in healthy controls. Meanwhile, the frequency of the G-1661 allele and GG-1661
      genotype is lower in MG patients. Linkage disequilibrium (LD) between each SNPs
      in promoter -1772, -1661, -318 and coding sequence 1 (CDS 1) +49 is apparent.
      sCTLA-4 levels in patients' sera are correlated with the haplotype and genotype.
      T/C-1772 and A/G-1661 SNPs change the sequence of transcription factor NF-1 and
      c/EBPbeta binding sites. DNA variants lose site-specific binding activity of
      transcription factor regulated by lectin ConA and PHA. CONCLUSION: There are
      strong positive linkages among four SNPs. C/T-1772 and A/G-1661 polymorphisms can
      result in inefficient transcription of CTLA-4 gene. T>C-1772 mutation also
      affects gene splicing. These SNPs may constitute a factor of susceptibility to
      disease.

PMID- 15583986
TI  - [Single nucleotide polymorphisms and point mutations of ataxia telangiectasia
      mutated gene in Chinese of Han ethnicity].
AB  - OBJECTIVE: To explore the single nucleotide polymorphisms (SNPs) and point
      mutations of ataxia telangiectasia mutated (ATM) gene in Chinese of Han
      ethnicity. METHODS: The target fragments of the exon 39, exon 61 and exon 63 of
      ATM gene were first amplified using PCR technique, then screened for the SNPs and
      point mutations using single strand conformation polymorphism (SSCP) technique,
      finally the representative bands were sequenced for the verification of the new
      single nucleotide polymorphisms and point mutations using the automatic DNA
      sequencing technique. RESULTS: Six new SNPs were found in the exon 39, intron 61
      and intron 63 of ATM gene. They are respectively the A/T polymorphisms at
      nucleotide 5689 and 5691 in exon 39, the T/G polymorphisms at nucleotide +69 and
      +99, the A/G polymorphism at nucleotide +94 in intron 61, the G/C polymorphism at
      nucleotide +17 in intron 63. Five new point mutations were found in the exon 61,
      intron 62 and exon 63 of ATM gene. They are respectively the T/G transversion at
      nucleotide 8618 in exon 61, the T/G transversion at nucleotide -13 in intron 62,
      the T/G transversion at nucleotide 8793, the G/A transitions at nucleotide 8816
      and 8848 in exon 63. The known three SNPs, the G/A polymorphism at nucleotide
      5557 in exon 39, the T/C polymorphism at nucleotide +104 in intron 61 and the T/C
      polymorphism at nucleotide -55 in intron 62, were verified in Chinese of Han
      ethnicity. CONCLUSION: There are great differences in the SNPs of ATM gene
      between Chinese of Han ethnicity and Caucasian.

PMID- 15583987
TI  - [Association between tumor necrosis factor-beta polymorphisms and coronary heart
      disease in a Chinese population].
AB  - OBJECTIVE: To investigate the association between tumor necrosis factor-beta (TNF
      beta) gene polymorphisms and coronary heart disease (CHD). METHODS: Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence
      specific primer-PCR (PCR-SSP) were used for the detection of TNF-beta genotype in
      210 patients with CHD and 186 healthy controls. The serum TNF-beta levels were
      measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The frequencies
      of CC, CA and AA genotypes of C804A in patients and controls were 25.7% and
      37.1%, 49.5% and 45.7%, 24.8% and 17.2%, respectively; there were statistically
      significant differences in the distributions of the genotypes (P<0.05) and the
      allele frequencies (P<0.05) between the two groups; the risk of suffering from
      CHD in those of AA and CA genotypes was 1.704 times that in those of CC genotype
      (OR=1.704, 95%CI: 1.109-2.617). However, there was no significant difference in
      the distribution of the genotype of G252A between the patients and controls,
      though significant difference was seen between the subgroups of the CHD group.
      The serum TNF-beta and high sensitive C-reactive protein (hsCRP) levels of the
      patients were significantly higher than those of the controls (P<0.05); however,
      there were no significant differences in regard to different TNF-beta genotypes
      among the patients and controls respectively. CONCLUSION: The single nucleotide
      polymorphism (SNP) at position 804 in the exon 3 of TNF-beta gene is associated
      with CHD and the allele A may be a risk factor for CHD in Chinese. The
      polymorphism of G252A may not play an important role in the pathogenesis of CHD.

PMID- 15583988
TI  - [Allele frequencies and species specificity of six short tandem repeat loci in
      Chinese population].
AB  - OBJECTIVE: To develop a set of new markers for forensic application, the authors
      have chosen 6 short tandem repeat(STR) loci to study the allele frequencies and
      species specificity in Chinese Han population in Chengdu. METHODS: One hundred
      and ten EDTA-blood samples were collected from the unrelated individuals in
      Chengdu city, Sichuan province. DNA was extracted by Chelex-100 and amplified by
      the polymerase chain reaction(PCR). Polyacrylamide gel electrophoresis (PAGE) and
      silver staining were used to analyze the PCR products. RESULTS: The polymorphisms
      of all 6 STR loci have been obtained in Chinese Han population in Chengdu, the
      alleles of D4S2366, D4S2367, D6S474, D6S1281, D2S1396 and D20S601 being 7, 7, 6,
      7, 5, 7, the observed heterozygosity of them being 0.802, 0.708, 0.770, 0.627,
      0.542, 0.672, the discrimination power of them being 0.887, 0.828, 0.849, 0.848,
      0.794, 0.865; and the power of exclusion of them being 0.602, 0.441, 0.544,
      0.325, 0.227, 0.386. Evaluated by comparison with the data from 14 different
      animals as controls, the 6 STR loci contain good specificity of human beings.
      CONCLUSION: The 6 STR loci are highly polymorphic and can play a key role in
      species identification. They are new candidate markers for forensic personal
      identification and paternity testing.

PMID- 15583989
TI  - [Polymorphism of NOS2A promoter -969(G>C) is associated with portal hypertension
      of liver cirrhosis].
AB  - OBJECTIVE: To determine whether polymorphism of NOS2A promoter -969G>C is
      associated with the portal hypertension of liver cirrhosis. METHODS: A case
      control study covering 106 patients with liver cirrhosis due to hepatitis B
      virus(HBV) in comparison with 108 controls was performed using PCR-restriction
      fragment length polymorphism. The NOS2A mRNA and protein expression in liver
      cirrhosis tissues were detected by reverse transcription-PCR and Western blot.
      The recombinant plasmids of NOS2A promoter luciferase reporter gene were
      constructed and were transfected transiently into HepG2 cells for analyzing the
      functional activity of the promoter. RESULTS: The frequencies of the C allele and
      GC genotype at NOS2A promoter -969G>C were significantly higher in portal
      hypertension group (16.9%, 33.8%) than in control group(8.8%, 17.6%)(P<0.05), and
      positive correlation (r=0.18) and association (OR=2.42) were noted. There was no
      significant difference in frequency distribution between single liver cirrhosis
      group and control group(P>0.05). The expressions of NOS2A mRNA and protein in
      liver cirrhosis tissues were more increased in C allele carriers with liver
      cirrhosis than in G allele carriers with liver cirrhosis, which led to higher
      functional activity of the promoter. Multivariate logistic regression analysis
      revealed that NOS2A polymorphism at promoter -969G>C is an independent novel risk
      factor for the occurrence of portal hypertension in patients with liver
      cirrhosis. CONCLUSION: The polymorphism of NOS2A promoter -969(G>C) is associated
      with portal hypertension of liver cirrhosis, which results in functional activity
      increase of NOS2A promoter and is an independent risk factor for portal
      hypertension.

PMID- 15583990
TI  - [Analysis of 32 cases of acute leukemia with abnormality of chromosome 7].
AB  - OBJECTIVE: To explore the incidence and prognostic significance of chromosome 7
      anomaly in acute leukemia. METHODS: Conventional cytogenetic analysis of R-band
      was used to detect the abnormalities of chromosome 7 in 410 acute leukemia
      patients. RESULTS: Thirty-two cases (7.8%) with abnormalities of chromosome 7, of
      which 19 (59.4%) had -7/7q-; 3(9.4%) had t(7;11); and the rest had other
      abnormalities such as der(7), +7, t(2;7), t(5;7), t(7;9), t(7;8) and dic(1;7).
      The incidence of -7/7q- in M0, M1 and M2 was higher than that in other subtypes
      of acute myeloid leukemia (AML). Twenty cases had additional cytogenetic
      aberrations, such as t(9;22) with -7, +8, -5. In 30 cases treated with
      chemotherapy, 11 cases acquired complete remission (CR) and the CR rate was lower
      than that for all concurrent cases of acute leukemia(36.7% vs 65.8%); the CR rate
      of AML with -7/7q- was lower than that of AML with normal karyotype(25% vs
      55.6%). There was no difference in the CR rate between acute lymphocytic
      leukemia(ALL) with -7/7q- and ALL with normal chromosome (57.1% vs 77.8%), but 4
      cases with -7/7q- which attained complete remission for a time relapsed early. In
      other 11 patients with additional chromosome 7 aberration, only 4 patients
      acquired CR. CONCLUSION: -7/7q- was the frequent aberration in chromosome 7
      anomaly, which was often detected in M0, M1 and M2. It might be associated with
      the pathogenesis of acute leukemia; the patients with chromosome 7 anomaly had
      poorer prognosis.

PMID- 15583991
TI  - [Accurate and rapid prenatal diagnosis of beta-thalassemia by a multiplex primer
      extension and denaturing high-performance liquid chromatography technique].
AB  - OBJECTIVE: To develop a primer-extension in combination with denaturing high
      performance liquid chromatography (PE-DHPLC)-based assay for prenatal diagnosis
      of the five most common beta-thalassemia mutations in Chinese. METHODS: The human
      beta-globin gene fragment was amplified by PCR, followed by a multiple PE
      reaction specific for each five mutations. Then the PE product mixtures were
      separated for genotyping of beta-globin gene mutations using fully-denaturing
      DHPLC analysis. RESULTS: In a blind study, prenatal diagnosis was performed on
      thirty-six at-risk families for beta-thalassemia major. Reverse dot blot (RDB)
      analysis was used to validate each result, showing an accuracy rate of 100% for
      PE-DHPLC in a total of 108 samples tested. Overall, by PE-DHPLC analysis, the
      authors could identify the genotypes involving the five mutations and normal
      alleles corresponding to 94.4% (102/108) and actually make final decision for
      prenatal diagnosis covering 97.2% (35/36). CONCLUSION: The PE-DHPLC protocol can
      be a simple, rapid, and highly accurate assay in the prenatal detection of common
      beta-thalassemia mutations.

PMID- 15583992
TI  - [Study on the recombinant adeno-associated virus vector carrying LacZ gene
      expression in the skeletal muscle].
AB  - OBJECTIVE: To look for a gene delivery route to the treatment of Duchenne
      muscular dystrophy(DMD). METHODS: The recombinant adeno-associated virus
      vector(rAAV) carrying a LacZ reporter gene was constructed. rAAVLacZ was
      delivered into the skeletal muscle tissue of C57/BL6 mice by intramuscular
      injection. Then an intraarterial delivery route was taken to reveal whether
      rAAVLacZ could transduce muscle tissue. RESULTS: (1) The LacZ gene was
      efficiently transduced and expressed persisting for 5 months after intramuscular
      injection. (2) The membrane of muscle and smooth muscle of vessel was widely
      transduced by intra-arterial delivery rAAVLacZ. CONCLUSION: These data provide
      the evidence that rAAVLacZ can efficiently transduce muscle for a long period.
      Improving intraarterial gene delivery will be promising means for rAAV-mediated
      gene therapy for generalized skeletal muscle of DMD.

PMID- 15583993
TI  - [Prenatal diagnosis of common chromosomal aneuploidies on uncultured amniotic
      fluid cells by fluorescence in situ hybridization].
AB  - OBJECTIVE: To evaluate the feasibility of using fluorescence in situ
      hybridization(FISH) for the detection of a few common chromosome aneuploidies on
      interphase nuclei of uncultured amniotic fluid cells. METHODS: Amniotic fluid
      samples were taken from 55 women at 16-32 weeks of pregnancy; interphase FISH was
      performed for diagnosing Down syndrome and aneuploidies of other four chromosomes
      13, 18, X and Y. Then the karyotypes from standard cytogenetic analysis after
      percutaneous umbilical blood sampling(PUBS) were compared to the FISH results.
      RESULTS: Each of the 55 uncultured amniotic fluid samples tested with FISH was
      enumerated 200 nuclei. Fifty-three samples were normal. Two samples were found to
      have trisomy 21(one is a case of standard trisomy 21 with three signals in all
      200 nuclei, the other is a mosaic trisomy 21). CONCLUSION: Interphase FISH
      analysis of uncultured amniotic fluid cells is a rapid, accurate and very
      sensitive method. It could be used in the prenatal cytogenetic laboratory.

PMID- 15583994
TI  - [Application of fluorescence in situ hybridization in the diagnosis of genetic
      diseases].
AB  - OBJECTIVE: To determine the value of fluorescence in situ hybridization (FISH) to
      the diagnosis of chromosome abnormality in genetic diseases and prenatal
      diagnosis. METHODS: FISH was performed using appropriate probes, including alpha
      satellite DNA probe, chromosome sequence specific probe and whole chromosome
      painting probe, to examine the blood samples from 36 patients who were suspected
      of having chromosome abnormality by conventional cytogenetics, and to examine the
      amniocytes from 45 pregnant women who were in need of prenatal diagnosis.
      RESULTS: Among 36 patients, the following karyotypes 45, X; 45, X/46, XX; 45,
      X/46, Xr(X); 46, X, i(Xq); 47, XXY; 46, XX, t(4;7); 47, XYY; 47, XXX; 47, XXY,
      inv(7); 46, XY, inv(7); 47, XX, +21 were detected by FISH. Of the fetuses of the
      45 pregnant women, two fetuses with chromosomal abnormalities were diagnosed by
      FISH; the karyotypes were 47, XX, +18 and 46, XY, der(15) t(Y;15) respectively.
      CONCLUSION: FISH can precisely and rapidly detect the chromosome abnormalities.
      It is a complement to the conventional cytogenetics and can be widely used in the
      diagnosis of genetic diseases and prenatal diagnosis.

PMID- 15583995
TI  - [Relationship of APOE gene polymorphism with subclasses of serum high density
      lipoprotein in hyperlipidemia].
AB  - OBJECTIVE: To investigate apolipoprotein E(apoE) polymorphism and its
      relationship with serum lipids and apolipoprotein, serum high density lipoprotein
      (HDL) subclasses in patients with hyperlipidemia(HL). METHODS: APOE genotype was
      assayed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). The subclasses of serum HDL in 112 patients with hyperlipidemia and
      73 healthy subjects were determined by two-dimensional gel electrophoresis in
      conjunction with immunodetection method. RESULTS: APOE3/3 genotypes and allele
      epsilon3 frequency in HL group and control group were both the highest. In HL
      group, the genotype of APOE2 had higher serum APOE/CIII ratio and lower HDL3b
      levels, compared with the genotype of APOE3 (P<0.05). In control group, the
      genotype of apoE2 had higher serum triglycerides, APOE levels and APOE/CIII
      ratio, compared with the genotype of APOE3 and APOE4 (P<0.05). CONCLUSION:
      Polymorphism of APOE gene may relate to the distribution of HDL particles.

PMID- 15583996
TI  - [The gene expression patterns of genetic P77PMC epilepsy-prone rats'
      hippocampus].
AB  - OBJECTIVE: To find out the differentially expressed genes in the hippocampus of
      the rats with genetic epilepsy so as to lay a foundation for exploring the
      pathogenesis of epilepsy by means of cDNA array technology. METHODS: Gene
      expression patterns in the hippocampus of the genetic epilepsy-prone P77PMC rats
      and normal Wistar rats were established using the alpha-32P-labeled cDNA probes
      hybridized with the Atlas Rat cDNA Expression Array, and then were analyzed by an
      image analysis instrument to get the differentially expressed genes. RESULTS:
      Fifteen genes were found having differential expression patterns in hippocampus
      between the P77PMC rats and the Wistar rats, while there may be many other
      differentially expressed genes left undiscovered due to having no appropriate
      image analysis software. And among the fifteen genes, the expression levels of
      twelve genes in the P77PMC rats were higher than those in the Wistar rats, while
      the expression levels of the other three genes were lower. The results of reverse
      transcription-polymerase chain reaction(RT-PCR) have demonstrated the reliability
      of cDNA arrays method. CONCLUSION: cDNA array is a powerful tool for identifying
      differential expression genes of epilepsy on large scales. There are several
      differentially expressed genes in hippocampus of the P77PMC rats and the Wistar
      rats. All these identified genes could play potentially important roles in the
      pathogenesis of epilepsy.

PMID- 15583997
TI  - [Association of the T(-344)C polymorphism of aldosterone synthase gene CYP11B2
      with essential hypertension in Xinjiang Kazakh isolated group].
AB  - OBJECTIVE: To investigate the association of the T(-344)C polymorphism of
      aldosterone synthase gene CYP11B2 with essential hypertension in Xinjiang Kazakh
      isolated population. METHODS: The study covered 186 hypertensives and 168
      normotensive controls in Xinjiang Kazakh population. The segment of CYP11B2 was
      amplified from DNA by polymerase chain reaction(PCR). The PCR products were
      digested by restriction endonuclease. RESULTS: The frequencies of C and T in
      hypertensive group (0.45 and 0.55) were not significantly different from those in
      the control group (0.43 and 0.57; chi-square test=0.380, P=0.537). The
      frequencies of CYP11B2 genotypes of CC, CT and TT were 0.20, 0.50 and 0.30 in
      hypertensives respectively, and 0.12, 0.61 and 0.27 in controls respectively.
      There was no significant difference in genotypes between hypertensive group and
      normotensive group (chi-square test=4.838, P=0.089). But the frequencies of CC
      genotype were higher in the female hypertensives than in the normotensive
      controls (chi-square test=6.104, P<0.05). CONCLUSION: The results suggested that
      the T(-344)C polymorphism of CYP11B2 gene may be associated with hypertension in
      female Kazakh population of Xinjiang Barlikun area.

PMID- 15583998
TI  - [Comparative genomic hybridization of esophageal squamous cell carcinoma and
      gastric cardia adenocarcinoma in high-incidence region of esophageal carcinoma,
      Linzhou Henan].
AB  - OBJECTIVE: To characterize the profiles of chromosome imbalance in esophageal
      squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) from the
      high incidence area in Henan. METHODS: Chromosomal aberrations of 37 samples of
      SCC and 30 GCA were analyzed by comparative genomic hybridization comparative
      genomic hybridization (CGH). RESULTS: It was found that the most frequently
      detected gains were on chromosome arm 8q (78%), and followed by 3q, 5p, 6q and
      7p. The most frequent loss was found on 3p (57%), and followed by 8p, 9q and 11q
      in SCC. For GCA, the most frequent gain was found on chromosome arm 20q (43%),
      and followed by 6q, 8q and 6p. The most frequent loss was on the chromosome 17p
      (57%), and followed by 19p, 1p and 4p. CONCLUSION: The present findings
      demonstrate that gains of 8q, 3q and 5p, and losses of 3p, 8p, and 9q are
      characteristic profile of chromosome imbalance in SCC, and the gains of 20q, 6q
      and losses of 17p, 19p and 1p are characteristic profile of chromosome imbalance
      in GCA, which provide important theoretic information for identifying and cloning
      novel SCC/GCA-related genes.

PMID- 15583999
TI  - [Nonsyndromic inherited hearing impairment caused by mtDNA double mutations of
      A1555G and 961 insC].
AB  - OBJECTIVE: To investigate the genotypes of mitochondrial DNA mutations of a large
      nonsyndromic inherited hearing impairment pedigree. METHODS: The diagnosis was
      validated by hearing test. Blood samples from the branch pedigree (33 members)
      and 6 sporadic patients were obtained. DNA was extracted from the leukocytes. The
      mitochondrial DNA target fragments were amplified by polymerase chain
      reaction(PCR). The 1555G, 3243G and 7445G mutations were detected by BsmA I, Apa
      I and Xba I restriction endonuclease digestion respectively. Some PCR products
      were analyzed by sequencing. RESULTS: Restriction endonuclease digestion
      identified that 17 patients from the pedigree carried 1555G mutation. All
      pedigree members, including patients and sporadic patients, did not have 3243G
      and 7445G mutation. In 6 patients of the pedigree DNA sequence analysis revealed
      double mutations, an A>G transition at position 1555 and a C insertion at
      position 961, whereas the unaffected relatives of the pedigree and sporadic
      patients did not have such mutations. None of them carried 3243G and 7445G
      mutation. CONCLUSION: Double mutations of A1555G and 961 insC in mitochondrial
      DNA 12S rRNA gene region may play a pivotal role in the pathogenesis of hearing
      loss in the large nonsyndromic inherited hearing impairment pedigree.

PMID- 15584000
TI  - [The haplotypes of three single nucleotide polymorphisms in caspase-3 gene in Han
      nationality of Zhejiang province in China].
AB  - OBJECTIVE: To investigate the single nucleotide polymorphisms (SNPs) and the
      distribution of their haplotypes in caspase-3 gene in Zhejiang Han nationality in
      China. METHODS: Denaturing high-performance liquid chromatography (DHPLC) and DNA
      sequencing were used to detect the SNPs in the regulatory region and the exons 2
      7 and their flanking sequences in caspase-3 gene. Expectation maximization (EM)
      algorithm was used for haplotype frequencies analysis and pairwise linkage
      disequilibrium test. RESULTS: (1) Three SNPs were identified in caspase-3 gene;
      the three sites C829A, A17532C and C20541T were located in 5' regulatory region,
      intron 4 and 3' regulatory region, respectively. (2) Strong linkage
      disequilibrium was found among these SNPs; site A17532C and C20541T were in
      complete linkage disequilibrium. (3) C-829/A-17532/C-20541 (54.3%) was the main
      haplotype of Zhejiang Han nationality. CONCLUSION: The above findings indicated
      there is strong linkage disequilibrium among the three SNPs in caspase-3 gene in
      Han nationality of Zhejiang province and the main haplotype of Han nationality is
      obviously different from that of North American.

PMID- 15584001
TI  - [Polymorphic analysis of four Y short tandem repeat loci in Han nationality of
      Hebei province in China].
AB  - OBJECTIVE: To investigate the distribution of the polymorphism of the Y
      chromosomal loci DYS438, DYS439, GATA A7.1 and GATA A7.2 among Han population in
      Hebei province. METHODS: With the use of PCR followed by polyacrylamide gel
      electrophoresis and silver staining, the allele frequencies of these loci in 164
      unrelated men of Han population were investigated. RESULTS: Four, five, five,
      four alleles were observed at the loci DYS438, DYS439, GATA A7.1 and GATA A7.2
      respectively; the frequencies of these alleles ranged from 0.0359 to 0.6587, from
      0.0179 to 0.4107, from 0.0122 to 0.4146 and from 0.0476 to 0.5238 respectively;
      the probability discrimination of these loci were 0.5121, 0.6811, 0.6679 and
      0.6327 respectively. Seventy different haplotypes were found at these loci.
      Thirty-six different haplotypes appeared only once. The power of discrimination
      of these four loci was 0.9480. CONCLUSION: The results demonstrate that these
      loci(DYS438, DYS439, GATA A7.1 and GATA A7.2) are good genetic markers with high
      determination power and can be applied to individual identification, especially
      in paternity test and the detection of mixed samples.

PMID- 15584002
TI  - [Genetic polymorphisms of six short tandem repeat loci in the Han population of
      Henan province in China].
AB  - OBJECTIVE: To investigate the allele frequencies of six short tandem repeats
      (STR) loci D12S391, D5S818, D18S51, PAHI3, D8S1179, D3S1358 in the Han population
      of Henan province and to obtain preliminary data. METHODS: DNA was extracted with
      phenol-chloroform from 140 EDTA-blood specimens of healthy unrelated individuals
      in Henan population; multiplex PCR technique and PAGE vertical electrophoresis
      were used to screen the genotype frequencies of six STR systems in Henan
      population. RESULTS: The test for Hardy-Weinberg equilibrium revealed that the
      genotype distribution was correspondent with the expected. The observed
      heterozygosities of six loci were 0.871, 0.769, 0.871, 0.773, 0.901, 0.722. The
      calculated discrimination power is 0.9999998, the calculated power of exclusion
      is 0.99845, the calculated matching probability is 2.39 x 10(-7). CONCLUSION: All
      of the six loci in this study have high power of discrimination and exclusion;
      they may be very useful genetic markers for individual identification, paternity
      test and genetics purposes.

PMID- 15584003
TI  - [Distribution of E-selectin gene polymorphism in the Zhuangs and Hans of Guangxi
      province in China].
AB  - OBJECTIVE: To unveil the distribution of E-selectin G98T polymorphism in exon 2
      and the S128R polymorphism in exon 4 of the Chinese Zhuang and Han ethnic groups
      in Guangxi province. METHODS: Polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP), gene sequencing and DNA sequencing were performed
      on 162 healthy Zhuangs and 170 healthy Hans. RESULTS: The allele frequencies of
      G, T for E-selectin polymorphism in the exon 2 were 94.8% and 5.2% in Zhuangs,
      95.3% and 4.7% in Hans, respectively; The allele frequencies of S, R for E
      selectin polymorphism in the exon 4 were 92.0% and 8.0% in Zhuangs, 95.9% and
      4.1% in Hans, respectively. There was significant difference in frequencies of
      genotype and allele in E-selectin S128R polymorphism between Zhuangs and Hans(chi
      square test=4.482, P=0.034). CONCLUSION: There was significant difference in the
      E-selectin S128R polymorphism between Zhuangs and Hans. There was no significant
      difference in the E-selectin G98T polymorphism between Zhuangs and Hans.

PMID- 15584004
TI  - Simultaneous determination of tryptophan and kynurenine in serum by HPLC with UV
      and fluorescence detection.
AB  - Tryptophan metabolism is disturbed in mental depression, and the induction of
      indoleamine 2,3-dioxygenase increases kynurenine production. In order to
      determine this disturbance in patients with chronic hepatitis C and receiving
      interferon-based immunotherapy, a new and specific HPLC protocol was elaborated.
      For tryptophan, the assay was linear from 6.25 to 100 micromol L(-1), and the
      limits of detection (LOD) and quantitation (LOQ) for the method were 0.7 and 8.0
      micromol L(-1). For kynurenine, the linearity of calibration was from 0.0625 to
      6.25 micromol L(-1), with LOD and LOQ of 2 and 3 nmol L(-1). Reproducibility and
      repeatability were satisfactory. The method allowed study of human blood serum.

PMID- 15584006
TI  - Effect of metal cationization on the tandem mass spectra of glycosyl
      dithioacetals.
AB  - The effect of metal cationization on the tandem mass spectra of glycosyl
      dithioacetals of glucose, mannose, galactose, rhamnose, arabinose and xylose was
      studied by electrospray ionization mass spectrometry under ammonium and metal
      (Li, Na, Ag and Cu) ion cationization conditions. The ammonium-cationized
      glycosyl dithioacetals fragment by loss of ammonia followed by either two
      molecules of EtSH or one molecule of EtSH and one molecule of H2O. Lithium
      cationization leads to additional eliminations such as EtSEt and EtSSEt and C-C
      cleavages. Elimination of EtSH is not observed under sodium cationization. Silver
      cationization, on the other hand, leads to additional fragmentations involving
      the elimination of silver as AgOH and AgSEt. Copper cationization results in
      adducts where copper has undergone a change of oxidation state from II to I. Li+,
      Ag+ and Cu+ cationization seem to favour cyclization resulting in elimination of
      EtSH. However, the mechanisms seem to be differently affected by different metal
      ions. Li+ and Ag+ cationization appear to be non-specific and favour cyclization
      involving C2-, C4- and C5-hydroxyl hydrogens, whereas Cu+ cationization seems to
      favour cyclization involving C4-hydroxyl hydrogen.

PMID- 15584007
TI  - Internal energy distribution in electrospray ionization.
AB  - Internal energies and energy distributions were studied using the 'survival
      yield' method developed previously. In addition to conventional benzylpyridinium
      salts, protonated esters (fragmenting by rearrangement) and protonated leucine
      enkephalin were also used, extending the validity of the technique. Fragmentation
      processes were studied in the cone voltage region and modeled by the RRKM-based
      MassKinetics program. The results show that the shapes of the energy
      distributions are similar to thermal distributions. The mean internal energies
      are very similar for all compound classes studied, and show a linear increase
      with collision energy in the 10-50 eV region.

PMID- 15584008
TI  - Electrospray ionization mass spectrometric analysis of chemical reactions of
      dissolution of selenium in strongly basic amines.
AB  - When elemental selenium was added to a strongly basic amine, 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN),
      the selenium started to dissolve and the solution turned dark brown. We
      investigated the chemical reaction of this selenium dissolution process by
      electrospray ionization mass spectrometry (ESI-MS). The study reveals for the
      first time that cleavage of Se-Se bonds by the amine initiates the reaction to
      form molecular Se2, which then abstracts hydrogen from the amine molecule. ESI-MS
      with the use of a nanospray technique was shown to be a useful tool for studying
      the dissolution of elements in strongly basic or acidic solvents.

PMID- 15584009
TI  - A validated liquid chromatographic/tandem mass spectrometric method for the
      determination of phencyclidine in microliter samples of rat serum.
AB  - A liquid chromatographic/tandem mass spectrometric method is described for the
      determination of phencyclidine (PCP) in small volumes of rat serum (e.g. 50
      microl). Samples were extracted using a mixed-mode strong cation-exchange column
      and then separated isocratically using a narrow-bore (2.1 mm i.d.) 3 microm
      Hypersil phenyl column and a mobile phase consisting of an ammonium formate
      buffer (pH 2.7) with 60% (v/v) methanol. Detection was accomplished using
      positive ion electrospray ionization in the multiple reaction monitoring mode.
      Mass spectra were obtained and peaks were observed at an m/z (% abundance) of 244
      (100), 159 (25), and 86 (89). Tandem mass spectra were also obtained from the m/z
      244 precursor ion with peaks observed at m/z 159 (100), 86 (96), and 91 (11).
      Optimum serum PCP sensitivity and precision were obtained at a transition of m/z
      244 --> 159. Matrix-associated ion suppression did not significantly affect the
      accuracy (100-112%) or precision (CV < or =8%) of the assay. The lower limit of
      quantitation was 1 ng ml(-1) in 50 microl of serum. The method was used to study
      the serum pharmacokinetics of PCP in rats after an intravenous bolus dose of PCP.

PMID- 15584010
TI  - Search of plasma markers for colorectal cancer by matrix-assisted laser
      desorption/ionization mass spectrometry.

PMID- 15584011
TI  - Electrospray ionization mass spectrometry of organic-inorganic materials:
      identification and gas-phase reactivity of functionalized octahedral rhenium(III)
      clusters.
AB  - Electrospray ionization mass spectrometry was used for the analysis of
      functionalized rhenium clusters such as [Re6Se8(o-Me2TTFPPh2)6]2+ (1), {Re6Se8[(o
      Me2TTF)2PPh]6}2+ (2) and [Re6Se8(MePPh2)6]2+ (3). The high-resolution mass
      spectra of the intact clusters, performed in dichloromethane, confirm the
      identification of the compounds by comparison with the theoretical isotopic
      distributions. Low-resolution full-scan mass spectra recorded at increasing
      desolvation cone voltage values allow the study of the intrinsic reactivity of
      ionic species. The survival yield curves illustrating the bimolecular reactivity
      of 1 and 2 suggest that a bisdimethyltetrathiafulvalene(phenyl)phosphine ligand
      increases the stability of the functionalized ML6(2+) cluster 2. In the case of
      the 3, instead of loss of a neutral ligand, ligand exchange is observed either
      with traces of water present in dichloromethane or with acetonitrile used as
      solvent.

PMID- 15584012
TI  - Amino acid cluster formation studied by electrospray ionization mass
      spectrometry.
AB  - The association properties of natural and non-natural amino acids were studied in
      detail using electrospray ionization mass spectrometry. The results show a highly
      diverse cluster formation behavior of amino acids. There are differences
      regarding the degree of clustering (average cluster size), the presence or
      absence of one or several 'magic' clusters of special stability and the influence
      of chirality on cluster stability. Cluster formation does not show a good
      correlation with simple physico-chemical properties (such as solubility),
      indicating that it is a specific process and not only a simple aggregation during
      evaporation/ionization. A systematic study of cluster formation of serine
      derivatives reveals that all functional groups play a prominent role in the
      binding of the magic octamer. The results support the idea of the zwitterionic
      character of the octamer. Electrospray ionization of the side-chain acetylated
      serine shows the formation of a very stable tetramer with a strong preference for
      homochirality. The results suggest that Ser8 is made up of two tetramer subunits,
      held together by hydrogen bonds of the side-chain.

PMID- 15584013
TI  - Sheath liquid interface for the coupling of normal-phase liquid chromatography
      with electrospray mass spectrometry and its application to the analysis of
      neoflavonoids.
AB  - A novel interface that allows normal-phase liquid chromatography to be coupled
      with electrospray ionization (ESI) is reported. A make-up solution of 60 mM
      ammonium acetate in methanol, infused at a 5 microl min(-1) flow-rate at the tip
      of the electrospray probe, provides a sheath liquid which is poorly miscible with
      the chromatographic effluent, but promotes efficient ionization of the targeted
      analytes. Protonated molecules generated in the ESI source were subjected to
      tandem mass spectrometric experiments in a triple-quadrupole mass spectrometer.
      The main fragmentation reactions were characterized for each analyte and specific
      mass spectral transitions were used to acquire chromatographic data in the
      multiple reaction monitoring detection mode. Results obtained during optimization
      of the sheath liquid composition and flow-rate suggest that the electrospray
      process was mainly under the control of the make-up solution, and that it forms
      an external charged layer around a neutral chromatographic mobile phase core.
      This sheath liquid interface was implemented for the analysis of some
      neoflavonoid compounds and its performance was evaluated. Limits of detection
      were established for calophillolide, inophyllum B, inophyllum P and inophyllum C
      at 100, 25, 15 and 100 ng ml(-1), respectively.

PMID- 15584014
TI  - Delayed extraction experiments using a repulsing potential before ion extraction:
      evidence of non-covalent clusters as ion precursor in UV matrix-assisted laser
      desorption/ionization. Part II--Dynamic effects with alpha-cyano-4
      hydroxycinnamic acid matrix.
AB  - Delayed extraction experiments were undertaken to gain a better insight into the
      dynamic effects involved in the ion formation in UV matrix-assisted laser
      desorption/ionization. Part I1 was devoted to a 2,5-dihydroxybenzoic (2,5-DHB)
      matrix. The results clearly demonstrated the existence and the role of high-mass
      precursors corresponding to a non-covalent matrix-analyte association in ion
      formation. In this complementary study, ion flight time and abundance were
      studied as a function of the delay extraction time using the matrix alpha-cyano-4
      hydroxycinnamic acid (HCCA). Under our instrumental conditions, where ejected
      ions experienced a low repulsing electric field before extraction, two main
      results were obtained: (i) two ion components are observed in the peak profiles
      depending on the repulsing field, a first, major component (I) similar to that
      observed for 2,5-DHB and a second, minor component (II) apparently triggered by
      the delayed extraction pulse, and (ii) ion time-of-flight variation vs delay time
      remained lower than that noted with 2,5-DHB matrix, indicating that the initial
      axial velocity is smaller. The initial kinetic energy of matrix and low molecular
      mass peptide ions for the component I is not high enough to overcome the
      repulsing potential in the delay time range (200-2200 ns) and we have to assume
      that ions have non-covalent clusters as precursors. Complete desolvation of these
      clusters-aggregates would be achieved through the extraction step. Simulations of
      the ion time-of-flight as a function of the delay time allow the determination of
      the average size of the precursors, typically 4500, 40000 and 50000 u for HCCA,
      ACTH 7-38 and bovine insulin quasi-molecular ion, respectively, assuming that the
      precursors are singly charged. The size of these ion precursors is greater than
      that of those generated for 2,5-DHB. For component II, ions are probably not
      solvated and they are directly desorbed from the target. Taking into account the
      results on HCCA and 2,5-DHB matrices and other results from the literature, a
      general model for ion formation based on clusters as ion precursors is proposed
      and discussed.

PMID- 15584015
TI  - Forced intercalation probes (FIT Probes): thiazole orange as a fluorescent base
      in peptide nucleic acids for homogeneous single-nucleotide-polymorphism
      detection.
AB  - Fluorescent base analogues in DNA are versatile probes of nucleic acid-nucleic
      acid and nucleic acid-protein interactions. New peptide nucleic acid (PNA) based
      probes are described in which the intercalator dye thiazole orange (TO) serves as
      a base surrogate. The investigation of six TO derivatives revealed that the
      linker length and the conjugation site decided whether a base surrogate conveys
      sequence-selective DNA binding and whether fluorescence is increased or decreased
      upon single-mismatched hybridization. One TO derivative conferred universal PNA
      DNA base pairing while maintaining duplex stability and hybridization
      selectivity. TO fluorescence increased up to 26-fold upon hybridization. In
      contrast to most other probes, in which fluorescence is invariant once
      hybridization had occurred, the emission of TO-containing PNA probes is
      attenuated when forced to intercalate next to a mismatched base pair. The
      specificity of DNA detection is therefore not limited by the selectivity of probe
      target binding and a DNA target can be distinguished from its single-base mutant
      under nonstringent hybridization conditions. This property should be of advantage
      for real-time quantitative PCR and nucleic acid detection within living cells.

PMID- 15584016
TI  - Simultaneous chiral analyses of multiple analytes: case studies, implications and
      method development considerations.
AB  - The field of chiral separations had a modest beginning some two decades ago.
      However, due to rapid technological advancement coupled with simultaneous
      availability of innovative chiral stationary phases and novel chiral
      derivatization agents, the field of chiral separations has now totally outpaced
      many other separation fields. Keeping pace with rapid changes in the field of
      chiral separations, investigators continue to add stereoselective
      pharmacokinetic, pharmacodynamic, pharmacologic and toxicological data of new
      and/or marketed racemic compounds to the literature. Examination of the evolution
      of chiral separations suggests that in the beginning many investigators attempted
      to separate and quantify a single pair of enantiomers, adopting either direct
      (separation made on a chiral stationary phase) or indirect (separation made
      following precolumn conversion of enantiomers to corresponding diastereomers)
      approaches. However, more recent trends in chiral separations suggest that
      investigators are attempting to separate and quantify multiple pairs of
      enantiomers with available technologies. Added to this, some interesting trends
      have been observed in many of the recently reported chiral applications,
      including preferences regarding internal standard selection, mobile phase
      contents and composition, sorting out issues with mass spectrometric detection,
      determination of elution order, analytical manipulations of metabolite(s) without
      reference standards and addressing some specificity-related issues. This review
      mainly focuses on chiral separations involving multiple chiral analytes and
      attempts to justify the need for such chiral separations involving multiple
      analytes. In this context, several cases studies are described on the utility and
      applicability of such chiral separations under discrete headings to provide an
      account to the readership on the implications of such tasks. The topics of case
      studies covered in this review include: (a) therapy markers--differentiation from
      drug abuse and/or applicability in forensics; (b) role in
      pharmacogenetic/polymorphic evaluation; (c) monitoring and understanding the role
      of parent and active metabolite(s) in clinical and preclinical investigations;
      (d) exploration on the pharmacokinetic utility of an active chiral metabolite vis
      a-vis the racemic parent moiety; (e) understanding the chirality play in
      delineating peculiar toxic effects; (f) exploration of chiral inversion
      phenomenon, and understanding the role of stereoselective metabolism. For the
      further benefit of readership, some select examples (n = 19) of the separation of
      multiple chiral analytes with appropriate information on chromatography,
      detection system, validation parameters and applicable conclusion are also
      provided. Finally, the review covers some useful considerations for method
      development involving multiple chiral analytes.

PMID- 15584018
TI  - Detection of a Plasmodium vivax erythrocyte binding protein by flow cytometry.
AB  - BACKGROUND: The malaria parasite Plasmodium vivax preferentially invades
      reticulocytes. It is therefore relevant for vaccine development purposes to
      identify and characterize P. vivax proteins that bind specifically to the surface
      of reticulocytes. We have developed a two-color flow cytometric erythrocyte
      binding assay (F-EBA) that has several advantages over traditional erythrocyte
      binding assays (T-EBAs) used in malaria research. We demonstrate the use of F-EBA
      using the P. vivax Duffy binding protein region II (PvDBP-RII) recombinant
      protein as a model. This protein binds to all erythrocytes that express the Duffy
      receptor (Fy) and discriminates binding between normocytes and reticulocytes.
      METHODS: F-EBAs were performed by incubating freshly isolated Aotus nancymai,
      Macaca mulatta, Saimiri boliviensis, and human erythrocytes with PvDBP-RII, a
      fluorescent anti-His tag detection antibody, and thiazole orange before flow
      cytometric analysis. T-EBAs employing immunoblot detection with an anti-His
      antibody were performed concomitantly. RESULTS: PvDBP-RII bound to A. nancymai,
      M. mulatta, and human Fy+ erythrocytes, but not human Fy- erythrocytes, by F-EBAs
      and T-EBAs. However, F-EBAs exhibited higher sensitivity and better concordance
      between experiments compared with T-EBAs. CONCLUSIONS: F-EBA is a rapid, simple,
      and reliable method for quantifying the ability of malaria proteins to bind to
      the surface of erythrocytes. F-EBA can discriminate binding between erythrocyte
      subpopulations without enrichment protocols and may be more reliable and
      sensitive than T-EBAs in identifying novel erythrocyte binding proteins.

PMID- 15584019
TI  - Chemical cytometry for monitoring metabolism of a Ras-mimicking substrate in
      single cells.
AB  - BACKGROUND: Chemical cytometry is an emerging technology that analyzes chemical
      contents of single cells by means of capillary electrophoresis or capillary
      chromatography. It has a potential to become an indispensable tool in analyses of
      heterogeneous cell populations such as those in tumors. Ras oncogenes are found
      in 30% of human cancers. To become fully functional products, oncogenic Ras
      proteins require at least three posttranslational modifications: farnesylation,
      endoproteolysis, and carboxyl-methylation. Therefore, enzymes that catalyze the
      three reactions, farnesyltransferase (FTase), endoprotease (EPase), and
      methyltransferase (MTase), are considered highly attractive therapeutic targets.
      In this work, we used chemical cytometry to study the metabolism of a
      pentapeptide substrate that can mimic Ras proteins with respect to their
      posttranslational modifications in solution. METHODS: Mouse mammary gland tumor
      cells (4T1) and mouse embryo fibroblasts (NIH3T3) were incubated with a
      fluorescently labeled pentapeptide substrate, 2',7'-difluorofluorescein-5
      carboxyl-Gly-Cys-Val-Ilu-Ala. Cells were washed from the substrate and
      resuspended in phosphate buffered saline. Uptake of the substrate by the cells
      was monitored by laser scanning confocal microscopy. Single cells were injected
      into the capillary, lysed, and subjected to capillary electrophoresis.
      Fluorescent metabolic products were detected by laser-induced fluorescence and
      compared with products obtained by the conversion of the substrate by FTase,
      EPase, and MTase in solution. Co-sampling of single cells with the in-vitro
      products was used for such comparison. RESULTS: Confocal microscopy data showed
      that the substrate permeated the plasma membrane and clustered in the cytoplasm.
      Further capillary electrophoresis and chemical cytometry analyses showed that the
      substrate was converted into three fluorescently labeled products, two of which
      were secreted in the culture medium and one remained in the cells. The
      intracellular product was present at approximately 100,000 molecules per cell.
      The three metabolic products of the substrate were found to be different from the
      products of its processing by FTase, EPase, and MTase in solution. CONCLUSIONS:
      This is the first report of chemical cytometry in the context of Ras-signaling
      studies. The chemical cytometry method used in this work will find applications
      in the development of suitable peptide substrates for monitoring enzyme
      activities in single cells.

PMID- 15584020
TI  - Phenotypic characteristics of mouse lung adenoma induced by 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanone.
AB  - The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK) in A/J mice was compared with that of normal lung tissue by
      suppression subtractive hybridization (SSH). The mRNAs of surfactant-associated
      protein A (SP-A) and lysozyme showed characteristically higher transcription in
      the adenoma tissue than in normal lung. High expression of both SP-A and lysozyme
      in tumor cells was confirmed by in situ hybridization (ISH). In normal lung,
      alveolar type II pneumocytes were positive for both SP-A and lysozyme, indicating
      that tumor cells retained the phenotypic characteristics of the murine alveolar
      type II pneumocytes. Previous studies of human adenocarcinomas have shown that
      the two proteins are expressed reciprocally; SP-A and lysozyme are differential
      markers of atypical adenomatous hyperplasia (AAH) and non-goblet cell type
      adenocarcinoma, and of goblet cell type adenocarcinoma, respectively. Thus, the
      present results indicate that the phenotype of NNK-induced A/J mouse adenoma
      differs from that of AAH, which is thought to be a preinvasive lesion of human
      adenocarcinoma.

PMID- 15584021
TI  - Hierarchical, model-based merging of multiple fragments for improved three
      dimensional segmentation of nuclei.
AB  - BACKGROUND: Automated segmentation of fluorescently labeled cell nuclei in three
      dimensional confocal images is essential for numerous studies, e.g.,
      spatiotemporal fluorescence in situ hybridization quantification of immediate
      early gene transcription. High accuracy and automation levels are required in
      high-throughput and large-scale studies. Common sources of segmentation error
      include tight clustering and fragmentation of nuclei. Previous region-based
      methods are limited because they perform merging of two nuclear fragments at a
      time. To achieve higher accuracy without sacrificing scale, more sophisticated
      yet computationally efficient algorithms are needed. METHODS: A recursive tree
      based algorithm that can consider multiple object fragments simultaneously is
      described. Starting with oversegmented data, it searches efficiently for the
      optimal merging pattern guided by a quantitative scoring criterion based on
      object modeling. Computation is bounded by limiting the depth of the merging
      tree. RESULTS: The proposed method was found to perform consistently better,
      achieving merging accuracy in the range of 92% to 100% compared with our previous
      algorithm, which varied in the range of 75% to 97%, even with a modest merging
      tree depth of 3. The overall average accuracy improved from 90% to 96%, with
      roughly the same computational cost for a set of representative images drawn from
      the CA1, CA3, and parietal cortex regions of the rat hippocampus. CONCLUSION:
      Hierarchical tree model-based algorithms significantly improve the accuracy of
      automated nuclear segmentation without sacrificing speed.

PMID- 15584022
TI  - Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and
      epidemiologic literature.
AB  - The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA
      base excision repair. The encoded DNA glycosylase excises 7,8-dihydro-8
      oxoguanine (8-OHdG), a highly mutagenic base produced in DNA as a result of
      exposure to reactive oxygen species (ROS). Polymorphisms in this gene may alter
      glycosylase function and an individual's ability to repair damaged DNA, possibly
      resulting in genetic instability that can foster carcinogenesis. In order to
      elucidate the possible impact of polymorphisms in hOGG1, we performed a
      literature review of both functional and epidemiologic studies that assessed the
      effects of these polymorphisms on repair function, levels of oxidative DNA
      damage, or associations with cancer risk. Fourteen functional studies and 19
      epidemiologic studies of breast, colon, esophageal, head and neck, lung,
      nasopharyngeal, orolaryngeal, prostate, squamous cell carcinoma of the head and
      neck (SCCHN), and stomach cancers were identified. Although the larger functional
      studies suggest reduced repair function with variant alleles in hOGG1, the
      evidence is generally inconclusive. There is some epidemiologic evidence that
      risk for esophageal, lung, nasopharyngeal, orolaryngeal, and prostate is related
      to hOGG1 genotype, whereas risk of breast cancer does not appear related. In
      studies that explored potential interactions with environmental factors, cancer
      risk for hOGG1 genotypes differed depending on exposure, especially for colon
      cancer. In summary, there is limited evidence that polymorphisms in hOGG1 affect
      repair function and carcinogenesis. Larger, well-designed functional and
      epidemiologic studies are needed to clarify these relationships, especially with
      respect to interactions with other DNA repair enzymes and interactions with
      environmental factors that increase carcinogenic load.

PMID- 15584023
TI  - Transient expression and flux changes during a shift from high to low riboflavin
      production in continuous cultures of Bacillus subtilis.
AB  - At the onset of glucose-limited continuous cultures, riboflavin production in
      recombinant Bacillus subtilis declines significantly within 3 generations. This
      phenomenon was specific to riboflavin production and was not correlated with any
      other physiological parameter. Physiological analyses excluded genetic
      degeneration or co-metabolism of previously generated overflow metabolites as
      possible causes for the riboflavin transients. By developing a novel method for
      (13)C-based metabolic flux analysis under non-steady-state conditions, we showed
      that the pentose precursors of riboflavin were exclusively synthesized via the
      non-oxidative pentose-phosphate (PP) pathway as long as riboflavin production was
      high. The complete redirection of carbon flux to the oxidative branch of the PP
      pathway was achieved at unaltered PP pathway gene expression and correlated with
      the declining riboflavin production. With the possible exception of a slight down
      regulation of the purine biosynthesis pathway, genome-wide expression analysis
      indicated that transcriptional regulation was not responsible for the production
      decline.

PMID- 15584024
TI  - Tumorigenesis in p27/p53- and p18/p53-double null mice: functional collaboration
      between the pRb and p53 pathways.
AB  - Mice lacking both p18(Ink4c) and p27(Kip1) develop a tumor spectrum similar to
      pRb(+/-) mice, and loss of p53 function accelerates tumorigenesis in pRb(+/-)
      mice. We hypothesized that codeletion of either p18 or p27 in conjunction with
      p53 deletion will also accelerate tumorigenesis. Mice lacking both p18 and p53
      develop several tumors not reported in either single null genotype, including
      hepatocellular carcinoma, testicular choriocarcinoma, hemangiosarcoma,
      leiomyosarcoma, fibrosarcoma, and osteosarcoma. Mice lacking both p27 and p53
      exhibit a decreased lifespan and develop unique tumors, including papillary
      carcinoma of the colon, hemangiosarcoma, and leiomyosarcoma. In both p18/p53 and
      p27/p53 double null genotypes, the incidence and spectra of tissues that develop
      lymphoma are also increased, as compared to the single null genotypes. The
      development of p27/p53 double null colon tumors correlates with secondary changes
      in cell-cycle protein expression and CDK (cyclin-dependent kinase) activity,
      perhaps contributing to the progression of colorectal cancer. We concluded that
      p18 and p27 can, not only functionally collaborate with one another, but also can
      independently collaborate with p53 to modulate the cell cycle and suppress
      tumorigenesis in a tissue-specific manner.

PMID- 15584025
TI  - Low-temperature pausing of cultivated mammalian cells.
AB  - There are currently two methods for maintaining cultured mammalian cells,
      continuous passage at 37 degrees C and freezing in small batches. We investigated
      a third approach, the "pausing" of cells for days or weeks at temperatures below
      37 degrees C in a variety of cultivation vessels. High cell viability and
      exponential growth were observed after pausing a recombinant Chinese hamster
      ovary cell line (CHO-Clone 161) in a temperature range of 6-24 degrees C in
      microcentrifuge tubes for up to 3 weeks. After pausing in T-flasks at 4 degrees C
      for 9 days, adherent cultures of CHO-DG44 and human embryonic kidney (HEK293
      EBNA) cells resumed exponential growth when incubated at 37 degrees C. Adherent
      cultures of CHO-DG44 cells paused for 2 days at 4 degrees C in T-flasks and
      suspension cultures of HEK293 EBNA cells paused for 3 days at either 4 degrees C
      or 24 degrees C in spinner flasks were efficiently transfected by the calcium
      phosphate-DNA coprecipitation method, yielding reporter protein levels comparable
      to those from nonpaused cultures. Finally, cultures of a recombinant CHO cell
      line (CHO-YIgG3) paused for 3 days at 4 degrees C, 12 degrees C, or 24 degrees C
      in bioreactors achieved the same cell mass and recombinant protein productivity
      levels as nonpaused cultures. The success of this approach to cell storage with
      rodent and human cell lines points to a general biological phenomenon which may
      have a wide range of applications for cultivated mammalian cells.

PMID- 15584026
TI  - Transient expression in tobacco leaves of an aglycosylated recombinant antibody
      against the epidermal growth factor receptor.
AB  - When generating stably transformed transgenic plants, transient gene expression
      experiments are especially useful to rapidly confirm that the foreign molecule of
      interest is correctly assembled and retains its biological activity. TheraCIM(R)
      (CIMAB S.A., Havana) is a recombinant humanized antibody against the Epidermal
      Growth Factor receptor (EGF-R), now in clinical trials for cancer therapy in Cuba
      and other countries. An aglycosylated version (Asn 297 was mutated for Gln 297)
      of this antibody was transiently expressed in tobacco leaves after vacuum
      mediated infiltration of recombinant Agrobacterium tumefaciens that carried a
      binary plasmid bearing the antibody heavy and light chain genes and plant
      regulation signals. Protein extracts from "agroinfiltrated" leaves were tested by
      ELISA and Western blot, showing that the fully assembled antibody was accumulated
      in plant tissues. The absence of plant specific glycans did not interfere in the
      assembling or in the activity of the plantibody, as demonstrated in this work.
      Indirect immunofluorescence demonstrated that the aglycosylated antibody
      expressed in plants recognizes the EGF-R expressed on the surface of A431 human
      tumor culture cells.

PMID- 15584027
TI  - Analysis of the course of Parkinson's disease under dopaminergic therapy:
      performance of "fast tapping" is not a suitable parameter.
AB  - In addition to clinical rating scales, instrumental methods are employed
      frequently for assessment of performance or motor deficits in Parkinson's disease
      (PD). Many studies have analyzed such parameters in cross-sectional studies. We
      employed a battery of tests to investigate fine motor performance over a period
      of 4 years in 411 de novo parkinsonian patients from the Prado study.
      Specifically, tapping and pegboard testing ("plugging") were evaluated and
      performance on these tests compared with clinical ratings. Plugging scores
      correlated well with tapping scores and clinical rating at each assessment
      timepoint. Both tests also showed significant differences to healthy controls.
      Nevertheless "fast tapping" was found to be less impaired than was plugging in de
      novo patients. Over time, it was observed that plugging scores, but not tapping
      scores, exhibited changes that paralleled movements in clinical score. Plugging
      scores exhibited a marked response to dopaminergic therapy whereas fast tapping
      showed no therapeutic response. Fast tapping is certainly not suitable for
      assessment of bradykinesia or hypokinesia, and does not respond to dopaminergic
      therapy.

PMID- 15584028
TI  - Development of a small-scale bioreactor: application to in vivo NMR measurement.
AB  - A perfused bioreactor allowing in vivo NMR measurement was developed and
      validated for Eschscholtzia californica cells. The bioreactor was made of a 10-mm
      NMR tube. NMR measurement of the signal-to-noise ratio was optimized using a
      sedimented compact bed of cells that were retained in the bioreactor by a
      supporting filter. Liquid medium flow through the cell bed was characterized from
      a mass balance on oxygen and a dispersive hydrodynamic model. Cell bed oxygen
      demand for 4 h perfusion required a minimal medium flow rate of 0.8 mL/min.
      Residence time distribution assays at 0.8-2.6 mL/min suggest that the cells are
      subjected to a uniform nutrient environment along the cell bed. Cell integrity
      was maintained for all culture conditions since the release of intracellular
      esterases was not significant even after 4 h of perfusion. In vivo NMR was
      performed for (31)P NMR and the spectrum can be recorded after only 10 min of
      spectral accumulation (500 scans) with peaks identified as G-6P, F-6P,
      cytoplasmic Pi, vacuolar Pi, ATP(gamma) and ADP(beta), ATP(alpha) and ADP(alpha),
      NADP and NDPG, NDPG and ATP(beta). Cell viability was shown to be maintained as
      (31)P chemical shifts were constant with time for all the identified nuclei, thus
      suggesting constant intracellular pH.

PMID- 15584029
TI  - Trigeminally induced startle in children with hyperekplexia.
AB  - To determine the physiological features of startle reactions in children with
      hereditary hyperekplexia, motor responses to auditory and trigeminal stimulation
      were investigated in 2 patients and 3 control subjects by means of multiple
      surface electromyographic recordings. The pattern of motor activation in auditory
      startle was similar in the two groups, although the responses in the patients
      were increased in terms of the extent of the responses. In the patients, nose
      taps elicited two separate responses in various muscles. The initial, short
      latency response was often elicited in all the muscles examined. This reflex was
      similar to the R1 component of the electrical blink reflex. In addition, the
      early reflex was immediately followed by the second response, which also appeared
      widely and was similar to R2 of the blink reflex. Taps on the supraorbital nerve
      elicited multiple startle patterns consisting of these two responses, although
      generalization was infrequent. In the control subjects, these responses were
      elicited in a few muscles. In the hyperekplectic children, both the early and
      second responses to trigeminal stimulation were increased, in addition to the
      audiogenic reflex. It was suggested that enhancement of these responses occurred
      due to hyperexcitability in the brainstem reticular formation in our patients.

PMID- 15584030
TI  - Novel parkin mutations detected in patients with early-onset Parkinson's disease.
AB  - A multiethnic series of patients with early-onset Parkinson's disease (EOP) was
      studied to assess the frequency and nature of parkin/PARK2 gene mutations and to
      investigate phenotype-genotype relationships. Forty-six EOP probands with an
      onset age of < 45 years, and 14 affected relatives were ascertained from Italy,
      Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and
      exon dosage using a new, cost-effective, real-time polymerase chain reaction
      method. Mutations were found in 33% of the indexes overall, and in 53% of those
      with family history compatible with autosomal recessive inheritance. Fifteen
      parkin alterations (10 exon deletions and five point mutations) were identified,
      including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9
      10 deletion. Homozygous mutations, two heterozygous mutations, and a single
      heterozygous mutation were found in 8, 6, and 1 patient, respectively.
      Heterozygous exon deletions represented 28% of the mutant alleles. The patients
      with parkin mutations showed significantly earlier onset, longer disease
      duration, more frequently symmetric onset, and slower disease progression than
      the patients without mutations, in agreement with previous studies. This study
      confirms the frequent involvement of parkin and the importance of genetic testing
      in the diagnostic work-up of EOP.

PMID- 15584031
TI  - Movement disorder emergencies.
AB  - Movement disorders may present acutely, and failure to recognize and exclude
      important differential diagnoses can result in significant morbidity or
      mortality. Unfortunately, much of the literature pertaining to this topic is
      scattered and not easily accessible. This review aims to address this deficit.
      Movement disorder emergencies are discussed according to their most likely mode
      of presentation. Diagnostic considerations and early management principles are
      reviewed, along with appropriate pathophysiology where relevant.

PMID- 15584032
TI  - Interrater agreement in the assessment of motor manifestations of Huntington's
      disease.
AB  - With prospects improving for experimental therapeutics aimed at postponing the
      onset of illness in preclinical carriers of the Huntington's disease (HD) gene,
      we assessed agreement among experienced clinicians with respect to the motor
      manifestations of HD, a relevant outcome measure for preventive trials in this
      population. Seventy-five clinicians experienced in the evaluation of patients
      with early HD and six non-clinicians were shown a videotape compiled from the
      film archives of the United States-Venezuela Collaborative HD Research Project.
      Observers were asked to rate a 2-3-minute segment of the motor examination for
      each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4
      (unequivocal extrapyramidal movement disorder characteristic of HD). As measured
      by a weighted kappa statistic, there was substantial agreement among the 75
      clinicians in the judgment of unequivocal motor abnormalities comparing scale
      ratings of 4 with ratings that were not 4 (weighted kappa = 0.67; standard error
      (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted kappa =
      0.28; SE = 0.10). Even under the artificial conditions of a videotape study,
      experienced clinicians show substantial agreement about the signs that constitute
      the motor manifestations of illness in subjects at risk for HD. We expect these
      findings to translate to a similar level of interobserver agreement in the
      clinical trial setting involving experienced investigators examining live
      patients.

PMID- 15584033
TI  - Nucleocytoplasmic distribution of opioid growth factor and its receptor in tongue
      epithelium.
AB  - The subcellular distributions of the opioid growth factor (OGF), [Met(5)]
      enkephalin, and opioid growth factor receptor (OGFr) in the epithelium of the rat
      tongue were determined in order to reveal structure-function relationships. Laser
      scanning confocal microscopic analysis showed that both OGF and OGFr were
      colocalized in the paranuclear cytoplasm and in the nuclei of keratinocytes in
      the stratum basale. Using immunoelectron microscopy and postembedding techniques,
      double labeling experiments disclosed that complexes of OGF-OGFr were colocalized
      on the outer nuclear envelope, in the paranuclear cytoplasm, perpendicular to the
      nuclear envelope in a putative nuclear pore complex, and in the nucleus adjacent
      to heterochromatin. Anti-OGF IgG alone was detected in the cytoplasm, and anti
      OGFr IgG alone was associated with the outer nuclear envelope. Study of chronic
      treatment with the opioid antagonist, naltrexone (NTX), which blocks opioid
      receptor binding, revealed the presence of OGFr immunoreactivity alone in the
      cytoplasm and the nucleus; some OGF-OGFr complexes were also observed.
      Colocalization of OGFr and karyopherin (importin) beta was recorded in the
      cytoplasm and nucleus. These results in tongue epithelium are the first to
      suggest that OGFr resides on the outer nuclear envelope, where OGF interacts with
      OGFr; that the OGF-OGFr complex translocates between cytoplasm and nucleus at the
      nuclear pore; and that the nuclear localization signal of OGFr interacts with
      karyopherin beta for nuclear transport. These novel data also indicate that
      signal transduction for cell proliferation appears to involve an OGF-OGFr complex
      that interfaces with chromatin in the nucleus. Moreover, the unique finding that
      OGFr was found in the cytoplasm and nucleus in NTX-treated specimens may suggest
      that NTX-OGFr complexes have the same pathway as OGF-OGFr.

PMID- 15584034
TI  - Myocardial expression and redistribution of GRKs in hypertensive hypertrophy and
      failure.
AB  - G-protein-coupled receptor kinases (GRKs) are involved in cardiac hypertrophy and
      failure. But their temporal expression and cellular localization during the
      development of hypertrophy and its transition to failure remains to be
      investigated. In this study, we determined the expression and subcellular
      distribution of GRK2, GRK3, GRK5, and GRK6 in cardiac myocytes of 2- to 24-month
      old spontaneously hypertensive heart failure (SHHF) rats. GRK2 increased in the
      intercalated disks in 6-, 12-, and 24-month-old SHHF rats, although total
      expression remained relatively constant from 2 to 24 months in both SHHF and
      normotensive rats. GRK3 expression progressively increased in 6-, 12-, and 24
      month-old SHHF rats and was significantly higher than in age-matched controls.
      Immunolabeling of GRK3 showed a typical pattern of cross-striations that
      colocalized with alpha-actinin and G(alphas) at Z-lines in both SHHF and control
      rats. GRK5 expression showed no change from 2 to 24 months in both SHHF and
      normotensive rats. Confocal analysis revealed nuclear translocation of GRK5 in
      myocytes of SHHF rats. GRK6 had a striated pattern colocalized with alpha-actinin
      at Z-lines in the cytoplasm and was also present in the intercalated disks of
      cardiac myocytes from both SHHF and control rats. GRK6 expression increased in 12
      and 24-month-old SHHF rats and was significantly higher than in age-matched
      controls. GRK6 labeling was reduced at the intercalated disks, but increased in
      the cytoplasm of cardiac myocytes from SHHF rats compared to age-matched
      controls. The increased expression of GRK3 and GRK6 and subcellular
      redistribution of GRK2, GRK5, and GRK6 in SHHF rats may be involved in abnormal
      remodeling of cardiac myocytes in hypertensive hypertrophy and failure.

PMID- 15584036
TI  - Torsional resistance as a principal component of the structural design of long
      bones: comparative multivariate evidence in birds.
AB  - Here we study the occurrence of torsion-resisting morphological and histological
      features (thin bone walls, circular shaft cross-section, oblique collagen fibers,
      and laminar tissue arrangement) in a sample of 168 long bones from wings and legs
      of 22 bird species. These structural parameters were measured in mid diaphyseal
      undemineralized cross-sections and analyzed using uni-, bi-, and multivariate
      (principal components analysis) data analysis techniques. We found that the four
      variables are significantly and positively correlated, and that covariation
      between variables accounts for as much as 58% of the total variation. These
      results suggest that torsion is a main determinant of the macro- and
      microstructural design of long bones in birds. Humerus, ulna, and femur generally
      possess torsion-resisting features, while other bones (radius, carpometacarpus,
      tibiotarsus, tarsometatarsus, and foot phalanx) rather show bending/axial load
      resisting structural properties. These results are congruent with in vivo strain
      data from the literature, which reported high torsional loading in humerus and
      ulna during flapping flight, but also in the subhorizontal avian femur during
      terrestrial locomotion. The precise function of the laminar tissue spatial
      arrangement, the role of pneumatization, and the influence of flight mode are
      discussed.

PMID- 15584035
TI  - Assessing age-related ossification of the petro-occipital fissure: laying the
      foundation for understanding the clinicopathologies of the cranial base.
AB  - The petro-occipital fissure (POF) lies within a critical interface of cranial
      growth and development in the posterior cranial fossa. The relationships between
      skeletal and soft tissues make this region especially important for examining
      biomechanical and basic biologic forces that may mold the cranial base and
      contribute to significant clinicopathologies associated with the structures
      located near the POF. Therefore, this study investigates the POF in adults in
      both preserved human cadavers and dried crania in order to determine if
      developmental changes can be observed and, if so, their value in age assessment
      as a model system for describing normal morphogenesis of the POF. This study
      demonstrates that tissue within the POF undergoes characteristic changes in
      ossification with age, the onset of which is considerably later than that of
      other synchondroses of the cranial base. Statistically, there is a moderate to
      strong correlation between age and stage of ossification within the POF. Further,
      male crania were observed to reach greater degrees of ossification at a younger
      age than female crania and that individual asymmetry in ossification of the
      tissue within the POF was not uncommon. An understanding of the basic temporal
      biological processes of the POF may yield insight into the development of
      clinicopathologies in this region of the cranial base.

PMID- 15584037
TI  - Cytological findings in a sample of peritoneal aspirate from a case of bile
      peritonitis.
AB  - Bile peritonitis (BP) is a rare and serious condition warranting urgent surgical
      intervention to prevent the high incidence of mortality. BP is ascribed to the
      leakage of bile into the peritoneal cavity usually due to a perforation of the
      gallbladder or common bile duct caused by stones or a trauma. The radiological
      studies are useful in suggesting the diagnosis. The cytological findings of BP
      have been reported rarely in the literature characterised by the presence of
      lakes of stringy bile material admixed with variable numbers of histiocytes,
      mesothelial cells, and some inflammatory cells. Recently, we have examined an
      aspirate sample of peritoneal fluid (PF) obtained under ultrasound guidance in a
      case of BP ascribed to the perforation of the gallbladder in a 19-yr-old female
      patient in which apart from occasional bile pigment-laden macrophages admixed
      with a few mesothelial cells and inflammatory cells, numerous crystalline
      structures of varying shapes, sizes, and colour with birefringence along with
      some microspheroliths were found. At operation, the abdominal cavity showed a
      large amount of bile and the gallbladder specimen showed two perforations and
      gangrenous cholecystitis with numerous yellow-brown somewhat friable stones. The
      foregoing findings in the aspirate appeared to be of interest because to the best
      of our knowledge, numerous crystalline structures along with the cytological
      features of BP have not been described in the English literature.

PMID- 15584038
TI  - Value of cytological imprints in the diagnosis of atypical lipomatous tumor.
AB  - The diagnosis of atypical lipomatous tumor by biopsy, requires careful
      examination of several slides, in order to look for atypical cells. We suggest
      that imprints of lipomatous tumors may play a complementary role in such a
      search, and report a case of a 74-yr-old woman with an atypical lipomatous tumor
      of the left thigh, in which imprints helped to make the diagnosis..

PMID- 15584039
TI  - Obituary: "alas poor FNA of breast-we knew thee well!".

PMID- 15584040
TI  - Fine-needle aspiration cytology of lipoblastoma: a report of two cases.
AB  - Lipoblastoma is an uncommon lipomatous tumor that typically occurs in infants and
      children. It may present as a single subcutaneous nodule or with multiple lesions
      (lipoblastomatosis). We describe fine-needle aspiration (FNA) cytologic features
      of two cases that presented as a subcutaneous lump in the scapular area and as a
      deeply located mass in the left arm. Smears showed fragments of adipose tissue
      that consisted of numerous vacuolated adipocytes with few stroma. Nuclei were
      small and located centrically, without indentations. Myxoid stromal material was
      a remarkable finding in one case. Both cases showed small delicate vessels,
      mainly in relation with the myxoid material. No necrosis, atypia, or mitotic
      figures were present. Cytologic features were characteristic enough to permit a
      specific diagnosis (adipose tumor suggestive of lipoblastoma). The differential
      diagnosis should consider lipoma with regressive changes, well-differentiated and
      mixoid liposarcoma. In addition to cytologic features, the patient's age is very
      useful for differentiation.

PMID- 15584041
TI  - Fine-needle aspiration cytology of pilomatrixoma of the arm and the role of cell
      block examination in the diagnosis.

PMID- 15584043
TI  - Fine-needle aspiration of renal angiomyolipoma: cytological findings and
      diagnostic pitfalls in a series of five cases.
AB  - Diagnosis of renal angiomyolipoma (AML) by fine-needle aspiration (FNA) may be
      difficult because cytological and radiological findings sometimes overlap with
      renal cell carcinoma (RCC) and liposarcoma. Five FNAs of AMLs were studied.
      Epithelioid and spindle stromal cells were arranged in loosely cohesive clusters
      and singly. The chromatin was evenly distributed and bland. Occasionally nuclear
      atypia was identified. Nuclei were oval to elongated, nucleoli were inconspicuous
      or absent, naked nuclei were present in three specimens, and intranuclear
      inclusions were present in two specimens. The cytoplasm was delicate and
      sometimes finely vacuolated. Adipose tissue was observed in two specimens. Thick
      walled vessels, mitoses, and necrosis were absent. Corresponding surgical
      material showed typical features of AML. In FNA, bland chromatin and
      inconspicuous nucleoli distinguish renal AML from RCC and liposarcoma. Adipose
      tissue is not universally present. Cellular atypia in conjunction with
      overlapping radiological findings with RCC and liposarcoma are potential
      diagnostic pitfalls. Immunocytochemical (ICC) stains may elucidate the correct
      diagnosis.

PMID- 15584044
TI  - Cytomorphological variation in two cases of melanotic neuroectodermal tumor of
      infancy.

PMID- 15584045
TI  - Herpes virus infection in peritoneal fluid: a case report and review of
      literature.
AB  - Herpetic infections in body cavity fluids are unusual and are rarely reported in
      the cytology literature. We report a case of a 74-yr-old woman who developed
      ascites after undergoing an elective laparoscopic cholecystectomy for biliary
      colic. Cytology of peritoneal fluid revealed changes in a herpes simplex virus
      (HSV) infection that was confirmed by immunocytological staining.

PMID- 15584046
TI  - Secretory carcinoma of the male breast: correlation of aspiration cytology and
      pathology.
AB  - Secretory carcinoma (SC) is a rare variant of breast carcinoma, which was first
      described in children and adolescents but it can occur at all ages. Very few
      cases have been reported in male patients. We describe the cytological and
      histopathological features of SC in a 79-yr-old man. Cytological findings
      demonstrated cohesive sheets of monotonous cells with round nuclei and small
      nucleoli. Most cells contained intracytoplasmic vacuoles, which are the key
      feature of an accurate diagnosis. Differential diagnosis with other tumors is
      discussed briefly.

PMID- 15584047
TI  - p16(INK4A) is a surrogate biomarker for a subset of human papilloma virus
      associated dysplasias of the uterine cervix as determined on the Pap smear.
AB  - Recently, p16(INK4A) has been identified as a biomarker for human papilloma virus
      (HPV)-induced dysplastic lesions of the cervix and it has been suggested that it
      may be a useful diagnostic aid for these lesions. This study therefore was
      performed to determine the utility of p16 expression in a series of Papanicolaou
      (Pap) smears collected in liquid medium and to determine its benefit, if any,
      over HPV testing. One hundred seven cases, including 23 negative cases, 34 with
      low-grade squamous intraepithelial lesion (LSIL), 16 with high-grade squamous
      intraepithelial lesion (HSIL), 29 with atypical squamous cells of uncertain
      significance (ASC-US), and 5 cases with ASC suspicious for HSIL (ASC-H), were
      evaluated for both p16 expression and HPV DNA. We observed p16 expression in only
      36% of all cases with abnormal cytology (30/84) and in 40% of all cases
      associated with high-risk HPV. The highest rate of positivity (80%) and the
      highest levels of expression (more than three to five positive cells/10x field)
      were seen in HSIL. Similar results were observed with ASC-H cases. This suggests
      that in equivocal cases, p16 may be used for confirmation of the diagnosis. On
      the other hand, p16 positivity was noted in only 21% of LSIL and ASC-US cases.
      This raises the interesting possibility, given that only a minority of LSIL cases
      progress on to higher-grade lesions, that p16 might be useful for triaging these
      patients for closer follow-up and/or further evaluation. Additional studies are
      required for confirmation.

PMID- 15584048
TI  - Fine-needle aspiration cytology of a liver metastasis of follicular dendritic
      cell sarcoma.
AB  - Follicular dendritic cell sarcoma (FDCS) is an uncommon neoplasm derived from
      FDCs in lymphoid tissue. Metastatic FDCS to the liver is rare. We present a case
      of a 65-yr-old woman who was referred to our institution 1 mo after splenectomy
      for FDCS of the spleen. An abdominal CT scan revealed a 2.0-cm liver lesion,
      which led to fine-needle aspiration (FNA) biopsy. Smears of the aspiration
      obtained were hypercellular showing a pleomorphic population of large oval to
      spindle-shaped tumor cells against a background of small mature lymphocytes,
      plasma cells, and necrotic debris. Tumor cells were arranged singly, in syncytial
      or fascicular patterns, and had a moderate amount of cytoplasm and indistinct
      cell borders. Nuclei had irregular nuclear membranes, finely granular to
      vesicular chromatin, and prominent nucleoli. Multinucleated and binucleated cells
      resembling Reed-Sternberg cells were noted occasionally. Mitotic figures,
      including atypical forms, were frequently identified. The diagnosis of
      "pleomorphic malignant spindle-cell neoplasm consistent with metastatic FDCS" was
      rendered and later confirmed by histological review and immunohistochemical
      staining of the subsequent liver resection specimen. Although cytological
      features of FDCS are characteristic, they are overlapping with those of many
      other tumors. We review the literature on this entity with emphasis on FNA
      cytomorphology, differential diagnosis, and immunohistochemical findings.

PMID- 15584049
TI  - Cytological features of epithelioid mesenchymal neoplasms: a study of 21 cases.
AB  - Epithelioid mesenchymal neoplasms (EMNs) are rare tumors that share cytological,
      histological, and immunohistochemical features with epithelial tumors. It is
      important to distinguish EMNs from epithelial tumors in cytology specimens due to
      their different clinical management and prognosis. The cytomorphological features
      of histologically confirmed EMN were reviewed. Twenty-one cytological specimens
      of EMN were evaluated and characterized by polygonal cells with moderate to
      abundant dense cytoplasm, prominent nucleoli, and pleomorphism. Additional
      findings included the presence of a distinct population of spindle cells,
      hemosiderin-containing cells, multinucleated cells, and granuloma-like structures
      in selected cases. Cytokeratin immunoreactivity was seen in two cases and was
      negative in one case. This study shows that the cytological features of EMNs and
      epithelial tumors overlap; nonetheless, some features are more helpful in
      suggesting EMN. A panel of immunocytochemical studies must include specific
      mesenchymal markers to avoid a misdiagnosis of carcinoma in cases of cytokeratin
      positive EMN.

PMID- 15584050
TI  - Proliferating myocytes-cytological mimicker of malignancy.

PMID- 15584051
TI  - Fine-needle aspiration cytology of intraductal papillary-mucinous tumors: a
      retrospective analysis.
AB  - Intraductal papillary-mucinous tumor (IPMT) of the pancreas has become the
      accepted terminology for a group of mucin-producing epithelial proliferations
      lying within ectatic segments of the main pancreatic duct or its large branches.
      These neoplasms generally are associated with an indolent course, characteristic
      endoscopic ultrasonographic (EUS) findings, and a variable histo- and
      cytomorphology ranging from hyperplasia to carcinoma. Cytological specimens
      obtained by endoscopic ultrasound-guided or percutaneous fine-needle aspiration
      (FNA) are characterized by a background containing abundant mucin in which are
      entrapped single or loosely cohesive clusters of neoplastic cells
      characteristically showing a goblet-cell morphology. The degree of nuclear
      atypia, cell crowding, and cell shape varies between smears within a single case
      and between cases. Cytomorphological examination, when coupled with EUS features,
      is accurate for the diagnosis of these lesions but often it underdiagnoses the
      grade of the neoplasm.

PMID- 15584052
TI  - Chromatin pattern alteration in malignant cells: an enigma.
AB  - Alteration of chromatin pattern is one of the most important clues to detect the
      malignant cell. However, the exact cause of change of chromatin pattern still is
      not clearly known. Recently, in last 20 yr, modern advanced technologies, such as
      fluorescent in situ hybridization (FISH), chromosome painting, green fluorescent
      protein (GFP) fusion technology, fluorescent recovery after photobleaching
      (FRAP), confocal microscopy, and multicolor four-dimensional imaging of living
      cell, have unfolded the mystery of the chromatin structure and dynamics. In this
      study, I have discussed the possible causes of chromatin change in malignant
      cells based on available recent information. Multiple factors are responsible for
      alteration of chromatin pattern in malignant cells. The important factors in this
      respect are chromatin relocation, DNA aneuploidy, change of nuclear matrix
      protein (NMP), histone protein alteration, abnormal nuclear lamin-chromatin
      interaction, and nuclear pore dysfunction. It is not impossible that the
      chromatin pattern alteration may be just a secondary change due to the
      interaction of fixative with chromatin and nonchromatinic substances in the
      nucleus.

PMID- 15584053
TI  - Effects of acetate and propionate on the performance of a photosynthetic biofilm
      reactor for sulfide removal.
AB  - The effects of acetate and propionate on the performance of a recently proposed
      and characterized photosynthetic biological sulfide removal system have been
      investigated with a view to predicting this concept's suitability for removing
      sulfide from wastewater undergoing or having undergone anaerobic treatment. The
      concept relies on substratum-irradiated biofilms dominated by green sulfur
      bacteria (GSB), which are supplied with radiant energy in the band 720-780 nm. A
      model reactor was fed for 7 months with a synthetic wastewater free of volatile
      fatty acids (VFAs), after which time intermittent dosing of the wastewater with
      acetate or propionate was begun. Such dosing suppressed the areal net sulfide
      removal rate by approximately 50%, and caused the principal net product of
      sulfide removal to switch from sulfate to elemental-S. Similarly suppressed
      values of this rate were observed when the wastewater was dosed continuously with
      acetate, and this rate was not significantly affected by changes in the
      concentration of ammonia-N in the feed. The main net product of sulfide removal
      was again elemental-S, which was scarcely released into the liquid, however.
      Sulfate reduction and sulfur reduction were observed when the light supply was
      interrupted and were inferred to be occurring within the irradiated biofilm. A
      preexisting conceptual model of the biofilm was augmented with both of these
      reductive processes, and this augmented model was shown to account for most of
      the observed effects of VFA dosing. The implications of these findings for the
      practicality of the technology are considered.

PMID- 15584054
TI  - "Parapharyngeal space" tumors: a cytopathological study of 24 cases on fine
      needle aspiration.
AB  - The parapharyngeal space (PPS) is a well-defined anatomic zone of loose
      connective tissue lying deep to the tonsil and lateral to the pharynx. Neoplasms
      arising within the PPS are rare. We retrospectively reviewed 24 PPS fine-needle
      aspirations (FNAs) performed at The Johns Hopkins Hospital over the past 16 years
      (1987-2002). Patients presented with neck pain, dysphagia, and/or intraoral
      swelling of varying duration. Radiographic imaging disclosed PPS masses, varying
      in size from 2.5 to 8 cm. The most common clinicoradiographic suspicion was a
      nerve sheath tumor. Six cases had FNA performed using a 23-gauge needle via a
      transoral approach in the outpatient suite whereas the remainder were aspirated
      via a 22-gauge Franseen needle under CT guidance. Six of 24 cases (25%) were
      nondiagnostic due to lack of adequate cellular material. Of the 18 cases
      considered diagnostic, there were nine (50%) pleomorphic adenomas (PAs); three
      (17%) squamous-cell carcinomas (SCC); and one each of oncocytoma, adenocarcinoma,
      not otherwise specified (NOS), adenoid cystic carcinoma, lipoma, neurofibroma,
      and non-Hodgkin lymphoma, together comprising the remaining 33%. Four of the six
      cases deemed nondiagnostic (consisting predominantly of blood) on subsequent
      tissue follow-up revealed paraganglioma (two cases), SCC (one case), and
      schwannoma (one case). PPS is an uncommon target of an FNA procedure. PPS masses
      represent a heterogeneous group of neoplasms of which PA appears most common,
      representing 50% of our diagnostic cases. The rate of nondiagnostic FNA samples
      is moderately high due to excessive bleeding encountered in this location and
      other technical problems relating to adequately targeting the lesion in close
      vicinity of major neck vessels.

PMID- 15584055
TI  - Randomized clinical trial of compression plus surgery versus compression alone in
      chronic venous ulceration (ESCHAR study)--haemodynamic and anatomical changes.
AB  - BACKGROUND: The aim of this study was to evaluate the anatomical and haemodynamic
      effects of superficial venous surgery and compression on legs with chronic venous
      ulceration. METHODS: Legs with open or recently healed ulceration and saphenous
      reflux were treated with multilayer compression bandaging or superficial venous
      surgery plus compression as part of a clinical trial. Venous duplex imaging was
      performed before treatment and at 1 year. Legs were stratified before surgery as
      having no deep reflux, segmental deep reflux or total deep reflux. Venous refill
      times (VRTs) were calculated before treatment and at 1 year using
      photoplethysmography, with and without a narrow below-knee cuff inflated to 80
      mmHg. RESULTS: Of 214 legs investigated, 112 were treated with compression and
      102 with compression plus surgery. Saphenous surgery abolished deep reflux in ten
      of 22 legs with segmental deep reflux and three of 17 with total deep reflux.
      Overall median (range) VRT increased from 10 (3-48) to 15 (4-48) s 1 year after
      surgery (P < 0.001). Preoperative change in VRT on application of a below-knee
      tourniquet correlated with actual change in VRT following surgery. CONCLUSION:
      Superficial venous surgery resulted in a significant haemodynamic benefit for
      legs with venous ulceration despite co-existent deep reflux; residual saphenous
      reflux was common.

PMID- 15584056
TI  - Middle Pleistocene human cranium from Tangshan (Nanjing), Southeast China: a new
      reconstruction and comparisons with Homo erectus from Eurasia and Africa.
AB  - The morphology and affinities of early and middle Pleistocene Homo erectus in
      East Asia have been explored since the late nineteenth century. A fragmentary
      hominid cranium (Nanjing no.1) recovered in Tangshan near Nanjing, China bears
      directly on these issues. In the present study, the morphological features of
      Nanjing no.1 are described and compared with Homo erectus from both Eurasia and
      Africa. Our results indicate that this middle Pleistocene hominid fossil should
      be referred to as Homo erectus. The sharing of typical Homo erectus features with
      African and European counterparts demonstrates that Homo erectus is a widely
      distributed lineage that evolved during the million years after its Pliocene
      origins. The differences between Nanjing no.1 and Zhoukoudian suggest certain
      level of regional variation in East Asian Homo erectus.

PMID- 15584057
TI  - Randomized clinical trial assessing impact of a lightweight or heavyweight mesh
      on chronic pain after inguinal hernia repair.
AB  - BACKGROUND: Severe chronic pain is a long-term problem that may occur after
      inguinal hernia repair. The aim of this randomized study was to compare pain of
      any severity at 12 months after inguinal hernia repair with a partially
      absorbable lightweight mesh (LW group) or with a non-absorbable heavyweight mesh
      (HW group). METHODS: Patients were assessed for pain at 1, 3 and 12 months by
      questionnaire, and were examined clinically at 12 months. RESULTS: Some 321
      patients were included in an intention-to-treat analysis, 162 in the LW group and
      159 in the HW group. At 12 months, significantly fewer patients in the LW group
      than in the HW group had pain of any severity: 39.5 versus 51.6 per cent
      (difference-12.1 (95 per cent confidence interval-23.1 to-1.0) per cent; P =
      0.033). The recurrence rate was higher in the LW group (5.6 versus 0.4 per cent;
      P = 0.037). Five of eight recurrences in LW group were associated with a single
      participating centre. CONCLUSION: Use of lightweight mesh was associated with
      less chronic pain but an increase in hernia recurrence after inguinal hernia
      repair. The latter may be related to technical factors associated with fixation
      of such meshes rather than any inherent defect in the mesh.

PMID- 15584058
TI  - Randomized clinical trial of open versus laparoscopic cholecystectomy in the
      treatment of acute cholecystitis.
AB  - BACKGROUND: The aim of this prospective trial was to determine whether surgical
      approach (open versus laparoscopic) had an impact on morbidity and postoperative
      recovery after cholecystectomy for acute cholecystitis. METHODS: Seventy patients
      who met the criteria for acute cholecystitis were randomized to open or
      laparoscopic cholecystectomy. The type of operation was unknown to the patient
      and all hospital staff involved in the postoperative care. RESULTS: The two
      groups were similar with respect to demographic and clinical characteristics.
      There were no significant differences in rate of postoperative complications,
      pain score at discharge and sick leave. In eight patients a laparoscopic
      procedure was converted to open cholecystectomy. Median operating time was 90
      (range 30-155) and 80 (range 50-170) min in the laparoscopic and open groups
      respectively (P = 0.040). The direct medical costs were equivalent in the two
      groups. Although median postoperative hospital stay was 2 days in each group, it
      was significantly shorter in the laparoscopic group (P = 0.011). CONCLUSION:
      Cholecystectomy for acute cholecystitis can be performed by either laparoscopic
      or open techniques without any major clinically relevant differences in
      postoperative outcome. Both techniques offer low morbidity and rapid
      postoperative recovery.

PMID- 15584059
TI  - Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on
      human osteoblasts in vitro.
AB  - BACKGROUND: The prolonged administration of heparin for prevention and treatment
      of venous thromboembolism has been associated with a risk of heparin-induced
      osteoporosis. Fondaparinux is a new antithrombotic drug that specifically
      inhibits factor Xa. Because of the known interactions of other antithrombotic
      agents with bone remodelling, the effects of fondaparinux on human osteoblasts
      were analysed in vitro. METHODS: Primary human osteoblast cell cultures were
      incubated with either the low molecular weight heparin dalteparin at
      concentrations of 30, 300 and 900 microg/ml or with fondaparinux at
      concentrations of 25, 50, 100, 150, 200 and 250 microg/ml. Cellular proliferation
      rate and protein synthesis were measured. Expression of genes encoding
      osteocalcin, collagen type I and alkaline phosphatase was examined by reverse
      transcriptase-polymerase chain reaction. RESULTS: Incubation with dalteparin led
      to a significant, dose-dependent inhibition of osteoblast proliferation,
      inhibition of protein synthesis, and inhibited expression of phenotype markers
      (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory
      effects were observed in the fondaparinux-treated cells. CONCLUSION: Fondaparinux
      did not inhibit osteoblast proliferation in vitro and may reduce the risk of
      heparin-induced osteoporosis associated with long-term heparin administration.

PMID- 15584060
TI  - Effect of hospital caseload on long-term outcome after standardization of rectal
      cancer surgery at a national level.
AB  - BACKGROUND: The purpose of this prospective study was to examine the influence of
      hospital caseload on long-term outcome following standardization of rectal cancer
      surgery at a national level. METHODS: Data relating to all 3388 Norwegian
      patients with rectal cancer treated for cure between November 1993 and December
      1999 were recorded in a national database. Treating hospitals were divided into
      four groups according to their annual caseload: hospitals in group 1 (n = 4)
      carried out 30 or more procedures, those in group 2 (n = 6) performed 20-29
      procedures, group 3 (n = 16) 10-19 procedures and group 4 (n = 28) fewer than ten
      procedures. RESULTS: The 5-year local recurrence rates were 9.2, 14.7, 12.5 and
      17.5 per cent (P = 0.003) and 5-year overall survival rates were 64.4, 64.0, 60.8
      and 57.8 per cent (P = 0.105) respectively in the four hospital caseload groups.
      An annual hospital caseload of less than ten procedures increased the risk of
      local recurrence compared with that in hospitals where 30 or more procedures were
      performed each year (hazard ratio 1.9 (95 per cent confidence interval (c.i.) 1.3
      to 2.7); P < 0.001). Overall survival was lower for patients treated at hospitals
      with an annual caseload of less than ten versus hospitals with 30 or more (hazard
      ratio 1.2 (95 per cent c.i. 1.0 to 1.5); P = 0.023). CONCLUSION: The rate of
      local recurrence was higher for hospitals with a low annual caseload of less than
      ten procedures than for hospitals with a high treatment volume of 30 or more.
      Patients treated in small hospitals also had a shorter long-term survival than
      those treated in large hospitals.

PMID- 15584061
TI  - Circumferential removal of the adventitia for cystic degeneration of the
      popliteal artery.

PMID- 15584062
TI  - Risk factors for anastomotic failure after total mesorectal excision of rectal
      cancer.
AB  - BACKGROUND: Anastomotic leakage is a major complication of rectal cancer surgery.
      The aim of this study was to investigate risk factors associated with symptomatic
      anastomotic leakage after total mesorectal excision (TME). METHODS: Between 1996
      and 1999, patients with operable rectal cancer were randomized to receive short
      term radiotherapy followed by TME or to undergo TME alone. Eligible Dutch
      patients who underwent an anterior resection (924 patients) were studied
      retrospectively. RESULTS: Symptomatic anastomotic leakage occurred in 107
      patients (11.6 per cent). Pelvic drainage and the use of a defunctioning stoma
      were significantly associated with a lower anastomotic failure rate. A
      significant correlation between the absence of a stoma and anastomotic dehiscence
      was observed in both men and women, for both distal and proximal rectal tumours.
      In patients with anastomotic failure, the presence of pelvic drains and a
      covering stoma were both related to a lower requirement for surgical
      reintervention. CONCLUSION: Placement of one or more pelvic drains after TME may
      limit the consequences of anastomotic failure. The clinical decision to construct
      a defunctioning stoma is supported by this study.

PMID- 15584063
TI  - Determination of therapeutic threshold in sacral nerve modulation for faecal
      incontinence.
AB  - BACKGROUND: The aim of the study was to determine the therapeutic stimulation
      threshold in patients with successful sacral nerve modulation for faecal
      incontinence. METHODS: Patients who had undergone successful permanent sacral
      nerve modulator implantation and had been followed up for a minimum of 3 months
      were included. The sensitivity threshold and motor threshold were determined and
      correlated with therapeutic response. Patients went home with the stimulator set
      at 0.6 V below the sensitivity threshold. Each week the voltage was increased by
      0.2 V until the sensitivity threshold was reached. The effects on anorectal
      physiology and continence were recorded. RESULTS: Eight patients (seven women)
      with a median age of 58.5 years were included. The median follow-up was 6.3
      months. The median sensibility threshold volume of rectal sensation was 50 ml,
      the median urge threshold volume was 140 ml and the median maximum tolerated
      rectal volume 240 ml. The median number of incontinence episodes and days per
      week affected by incontinence decreased from 5.0 and 3.8 before operation to 0.7
      and 0.7 respectively after follow-up for 3 months. At anorectal manometry the
      median resting and stimulation anal canal pressures were 57 and 85 mmHg
      respectively, and remained constant over time. The therapeutic response threshold
      was significantly lower than the sensitivity threshold (median 1.6 versus 1.7 V;
      P = 0.042). The median motor threshold was 2.1 V, significantly higher than the
      sensitivity threshold (P = 0.009). The stimulation threshold for suboptimal
      therapeutic response was 1.4 V. In five of the eight patients the therapeutic
      response threshold was the same as the sensitivity threshold. CONCLUSION: Sacral
      nerve modulation can produce a therapeutic effect below the sensitivity
      threshold. A lower stimulation voltage increases the lifespan of the pulse
      generator.

PMID- 15584064
TI  - Postdefaecation pain syndrome after circular stapled anopexy is abolished by oral
      nifedipine.
AB  - BACKGROUND: Controversy has surrounded the technique of circular stapled anopexy
      since an isolated report of a high incidence of persistent postdefaecation pain
      following the procedure. The characteristics, clinical course and management of
      this complication have not been described. METHODS: Within an ongoing multicentre
      randomized clinical trial comparing circular stapled anopexy with closed
      haemorrhoidectomy, 77 patients underwent circular stapled anopexy. Follow-up was
      at 6, 12, 24 and 48 weeks. Patients underwent transanal ultrasonography, anal
      electrosensitivity testing and manometry. RESULTS: Of the 77 patients who had
      circular stapled anopexy, three men reported new-onset postdefaecation pain that
      compromised lifestyle, including ability to return to work. All three had
      sphincter hypertonicity on digital and manometric examination but were refractory
      to topical 0.2 per cent glyceryl trinitrate ointment. The addition of oral
      nifedipine 20 mg twice daily did not alter anal sphincter pressures but rapidly
      abolished symptoms and restored quality of life. CONCLUSION: Postdefaecation pain
      is a specific complication of circular stapled anopexy, affecting a small
      percentage of patients. Men with a high anal sphincter pressure appear to be at
      risk. Although the exact aetiology remains unclear, it is likely that rectal
      rather than anal sphincter muscle is affected. Oral nifedipine represents an
      effective therapy.

PMID- 15584065
TI  - Test of histological methods of determining chronology of accentuated striae in
      deciduous teeth.
AB  - One of the difficulties that has prevented Wilson bands, internal defects of
      enamel growth, from achieving maximum usefulness as indicators of stress in
      bioarchaeological studies is the inaccuracy of the methods for determining ages
      of defect occurrence. This study tests a technique that uses microstructural
      growth markers of enamel to establish the chronology of Wilson bands in deciduous
      teeth. A sample of 274 teeth from 127 subadults from an Imperial Roman necropolis
      was sectioned and examined under a microscope. The sample ranged in age at death
      from birth to 13 years. Sixty-four teeth from 50 individuals were found to have
      447 Wilson bands in total. Of those contributing multiple teeth to the sample, 13
      individuals had at least one Wilson band in each of two teeth that could be
      identified as having been formed coevally. These provided the basis for testing
      the methodology. Paired t-tests found no significant differences between the
      chronologies of matched pairs in the two teeth, with mean ages from each
      differing by less than 1 day. The authors propose a hypothesis that explains the
      development of Wilson bands, and classifies them within the context of other
      features of enamel. The most important implications arising from this paper are:
      1) aging methods using microstructural growth markers can be applied to deciduous
      teeth; 2) physiological stressors leave different traces in enamel, depending on
      severity and time of occurrence relative to total crown development; 3) no
      threshold level exists; all physiological stress will leave a record; 4)
      therefore, no minimal definition of a Wilson band can be delineated that
      recognizes all such events; 5) implying that studies using them will only
      identify minimum rates of occurrence.

PMID- 15584066
TI  - Sentinel node biopsy to evaluate the metastatic dissemination of oesophageal
      adenocarcinoma.
AB  - BACKGROUND: The aim of this study was to determine the feasibility and accuracy
      of sentinel lymph node (SLN) biopsy for oesophageal adenocarcinoma. METHODS:
      Fifty-seven patients with adenocarcinoma of the lower oesophagus (n = 40) or
      gastric cardia (n = 17) underwent endoscopic peritumoral injection of (99m)Tc
      radiolabelled nanocolloid before en bloc resection with extended lymphadenectomy.
      SLNs were identified during surgery using a handheld gamma probe and the pattern
      of radioactive uptake was quantified after operation. All 1667 resected lymph
      nodes were examined immunohistochemically for micrometastases. RESULTS: SLNs were
      identified in all 57 patients. They contained metastases (n = 32) or
      micrometastases (n = 3) in 35 of 37 node-positive patients and there were two
      false-negative studies. The overall accuracy of SLN biopsy was 96 per cent and
      SLNs were more likely to contain tumour than other lymph nodes (P < 0.001).
      Tumour-infiltrated nodal stations had a higher proportion of radioactive uptake
      (P < 0.001). Lower oesophageal tumours had a greater proportion of SLNs (P =
      0.018), radioactive uptake (P < 0.001) and malignant nodes (P = 0.004) in the
      mediastinum than gastric cardia tumours. CONCLUSION: The sentinel node concept is
      applicable to oesophageal adenocarcinoma and could be used to tailor the extent
      of lymphadenectomy. There is a close relationship between patterns of radioactive
      uptake and lymphatic tumour dissemination, which differ for lower oesophageal and
      gastric cardia tumours.

PMID- 15584067
TI  - Investigating the form-function interface in African apes: Relationships between
      principal moments of area and positional behaviors in femoral and humeral
      diaphyses.
AB  - Investigations of cross-sectional geometry in nonhuman primate limb bones
      typically attribute shape ratios to qualitative behavioral characterizations,
      e.g., leaper, slow climber, brachiator, or terrestrial vs. arboreal quadruped.
      Quantitative positional behavioral data, however, have yet to be used in a
      rigorous evaluation of such shape-behavior connections. African apes represent an
      ideal population for such an investigation because their relatedness minimizes
      phylogenetic inertia, they exhibit diverse behavioral repertoires, and their
      locomotor behaviors are known from multiple studies. Cross-sectional data from
      femoral and humeral diaphyses were collected for 222 wild-shot specimens,
      encompassing Pan paniscus and all commonly recognized African ape subspecies.
      Digital representations of diaphyseal cross sections were acquired via computed
      tomography at three locations per diaphysis. Locomotor behaviors were pooled
      broadly into arboreal and terrestrial categories, then partitioned into
      quadrupedal walking, quadrumanous climbing, scrambling, and suspensory
      categories. Sex-specific taxonomic differences in ratios of principal moments of
      area (PMA) were statistically significant more often in the femoral diaphysis
      than the humeral diaphysis. While it appears difficult to relate a measure of
      shape (e.g., PMA ratio) to individual locomotor modes, general locomotor
      differences (e.g., percentage arboreal vs. terrestrial locomotion) are discerned
      more easily. As percentage of arboreal locomotion for a group increases, average
      cross sections appear more circular. Associations between PMA ratio and specific
      locomotor behaviors are less straightforward. Individual behaviors that integrate
      eccentric limb positions (e.g., arboreal scrambling) may not engender more
      circular cross sections than behaviors that incorporate repetitive sagittal
      movements (e.g., quadrupedal walking) in a straightforward manner.

PMID- 15584068
TI  - Dispersion dimorphism in human populations.
AB  - The aim of this paper is to verify the existence of dispersion (or variability)
      dimorphism in several anthropometric traits, i.e., some skeletal, muscular, and
      adipose dimensions, and to provide an evaluation of this scarcely considered
      aspect of sex differences. This research focuses on two human samples from two
      different European regions, Sardinia (Italy) and the Basque Country (Spain).
      Twenty-three anthropometric measurements were taken. A first qualitative analysis
      was carried out comparing the profiles of the coefficients of variation of each
      variable in both sexes. Secondly, the equality of variability was verified with
      different tests. In the normal case, Student's t-test, as proposed by Sokal and
      Braumann ([1980] Syst. Zool. 29:50-63), was applied. In the more general case, it
      was necessary to resort to resampling techniques. A suitable bootstrap test was
      constructed and the results were compared, when possible, with those obtained by
      other methods. The measurements showed parallel trends in the two populations. In
      particular, subcutaneous skinfolds showed significant dispersion dimorphism, with
      the greatest coefficients of variation in men. We suggest that this result was
      linked to stronger canalization in female dimensions related to the reproductive
      function and influenced by sociocultural factors. We also suggest defining
      dispersion dimorphism, whose existence is confirmed by the results presented in
      this paper, as a descriptive pattern of phenotype variability in both sexes that
      can be specific of a given class of anthropometric traits.

PMID- 15584069
TI  - Land, language, and loci: mtDNA in Native Americans and the genetic history of
      Peru.
AB  - Despite a long history of complex societies and despite extensive present-day
      linguistic and ethnic diversity, relatively few populations in Peru have been
      sampled for population genetic investigations. In order to address questions
      about the relationships between South American populations and about the extent
      of correlation between genetic distance, language, and geography in the region,
      mitochondrial DNA (mtDNA) hypervariable region I sequences and mtDNA haplogroup
      markers were examined in 33 individuals from the state of Ancash, Peru. These
      sequences were compared to those from 19 American Indian populations using
      diversity estimates, AMOVA tests, mismatch distributions, a multidimensional
      scaling plot, and regressions. The results show correlations between genetics,
      linguistics, and geographical affinities, with stronger correlations between
      genetics and language. Additionally, the results suggest a pattern of
      differential gene flow and drift in western vs. eastern South America, supporting
      previous mtDNA and Y chromosome investigations.

PMID- 15584070
TI  - Assessing the variation in individual frontal sinus outlines.
AB  - It is often suggested that the frontal sinus morphology of no two individuals is
      alike, and that the configuration of the frontal sinus is as unique to an
      individual as his or her fingerprints. However, no empirical, quantitative
      testing of the uniqueness of frontal sinus outlines has ever been performed. Such
      testing is necessary for frontal sinus identifications to be admissible in many
      courts. This study investigated frontal sinus outline variability using elliptic
      Fourier analysis (EFA), a geometric morphometric approach that fits a closed
      curve to an ordered set of data points, generating a set of coefficients that can
      be used to reproduce the outline. Two-dimensional representations of 808 frontal
      sinuses (as seen in posterior-anterior cranial radiographs) were digitized, and
      differences in their shapes were assessed quantitatively by comparing the
      Euclidean distances between EFA-generated outlines. Results show that Euclidean
      distances between outlines of different individuals are significantly larger than
      those between replicates of the same individual, and typicalities show that the
      probability of finding two different individuals with Euclidean distances less
      that that between a particular case's replicate is very small. Thus, there is a
      quantifiable and significant difference between the shapes of individuals'
      frontal sinus outlines.

PMID- 15584071
TI  - Direct coupling of pyrroles with carbonyl compounds: short enantioselective
      synthesis of (S)-ketorolac.

PMID- 15584072
TI  - Ontogenetic bases of canine dimorphism in anthropoid primates.
AB  - This study tests hypotheses regarding the ontogeny of canine tooth size
      dimorphism in five anthropoid primate species (Saguinus fuscicollis, Macaca
      mulatta, Cercocebus atys, Papio hamadryas, and Mandrillus sphinx). Canine
      measurements and chronological age data are analyzed to determine if bimaturism,
      a sex difference in the age at which eruption ceases, accounts for canine tooth
      sexual dimorphism. Canine height measurements are evaluated through a variety of
      regression techniques. Results show a lack of sexual dimorphism in Saguinus.
      While size dimorphism is absent in the deciduous teeth of all species analyzed,
      the adult teeth in cercopithecines become increasingly dimorphic through
      ontogeny. Female adult tooth eruption regularly precedes male tooth eruption, and
      regression-based eruption trajectories for both sexes intersect at about the age
      at which the female tooth reaches adult size. Males erupt the tooth later and
      more rapidly than females. Males also reach a larger adult size than females by
      erupting the tooth for much longer periods of time. Bimaturism is primary in the
      production of dimorphism, but rates of eruption show modest variation. These
      results point to the scheduling of sexual selection through intermale competition
      as a primary factor determining male eruption timing, rates of eruption, and
      adult size. Life history factors may play a role in determining the relations
      between the scheduling of intrasexual competition and canine eruption. Female
      contributions to sexual dimorphism are apparent in these species, suggesting that
      similar levels of dimorphism can be attained through diverse ontogenetic
      pathways.

PMID- 15584073
TI  - MoCalc: a new graphical user interface for molecular calculations.
AB  - A new computer program called MoCalc (Molecular Calculations) has been designed
      to help the computational chemistry practitioner in the task of performing and
      analyzing molecular calculations. MoCalc is a graphical user interface for the MO
      calculation programs Gamess and Mopac, and uses Rasmol and Babel for molecule
      display and file conversion, respectively. In its initial version, MoCalc can
      execute the following operations: (a) create and handle Gamess and Mopac input
      files; (b) import any kind of molecular geometry supported by Babel and paste it
      as Cartesian, internal, or Gaussian-type coordinates on the input file; (c)
      convert Gamess and Mopac output files to inputs of both programs; (d) edit and
      validate the keywords that control the Gamess and Mopac calculation procedure;
      (e) display the input (Mopac) and output (Gamess and Mopac) molecular geometries;
      (f) run single or multiple (batch) calculations, either interactively or in
      background; (g) automatically open the output files as soon as the calculation
      finishes; (h) extract results from the output files, such as energy, charges,
      dipole, population analysis, wave function, bond orders, and valence analysis,
      and display them in spreadsheets; (i) calculate reactivity indices derived from
      the frontier orbital theory and the root-mean-square (rms) deviation of input and
      output geometries. All the results generated by MoCalc can be promptly
      transferred to text editors and electronic spreadsheets, which facilitate a
      detailed subsequent analysis and the publication of the results. MoCalc can also
      perform graphical and numerical comparative analysis of the some results when
      more than one output file is loaded. The program was coded in Visual Basic and
      runs in Windows 95/98/NT4/ME/2000/XP environments.

PMID- 15584074
TI  - Reduced-size polarized basis sets for calculations of molecular electric
      properties. I. The basis set generation.
AB  - Following the recent studies of basis sets explicitly dependent on oscillatory
      external electric field we have investigated the possibility of some further
      truncation of the so-called polarized basis sets without any major deterioration
      of the computed data for molecular dipole moments, dipole polarizabilities, and
      related electric properties of molecules. It has been found that basis sets of
      contracted Gaussian functions of the form [3s1p] for H and [4s3p1d] for the first
      row atoms can satisfy this requirement with particular choice of contractions in
      their polarization part. With m denoting the number of primitive GTOs in the
      contracted polarization function, the basis sets devised in this article will be
      referred to as the ZmPol sets. In comparison with earlier, medium-size polarized
      basis sets (PolX), these new ZmPol basis sets are reduced by 2/3 in their size
      and lead to the order of magnitude computing time savings for large molecules.
      Simultaneously, the dipole moment and polarizability data remain at almost the
      same level of accuracy as in the case of the PolX sets. Among a variety of
      possible applications in computational chemistry, the ZmPolX are also to be used
      for calculations of frequencies and intensities in the Raman spectra of large
      organic molecules (see Part II, this issue).

PMID- 15584075
TI  - Reduced-size polarized basis sets for calculations of molecular electric
      properties. II. Simulation of the Raman spectra.
AB  - The accuracies of the calculated vibrational frequencies and Raman intensities
      given by two new, highly compact Pol-type basis sets, Z2PolX and Z3PolX, have
      been determined and compared to the 6-31G(d), PolX, and aug-cc-pVTZ basis sets.
      Calculation of accurate Raman intensities has previously required large basis
      sets, but the ZmPolX basis sets are smaller even than PolX, which are the most
      compact basis sets able to calculate accurate Raman intensities. For the largest
      compound studied, C5H10O2, Z3PolX required more than an order of magnitude less
      CPU time than PolX, which has been shown to be 10 times faster than aug-cc-pVTZ.
      Two sets of test molecules were studied: one was a series of small molecules for
      which experimental values for absolute Raman activities were available; the
      second was a series of medium-sized molecules (mainly common organic solvents)
      where only relative Raman band intensities were available. The accuracies of the
      Raman intensities given by both of the ZmPolX basis sets were good compared to
      those of the PolX and aug-cc-pVTZ sets, and much better than the 6-31G(d) values.
      The errors in even unscaled frequency values <2000 cm(-1) were also acceptable
      and were slightly lower for Z3PolX than Z2PolX (30 cm(-1) vs. 48 cm(-1)). The
      combination of good intensity and frequency data meant that for the medium-sized
      organic molecules there was a close correspondence between the simulated Raman
      spectra and experimental data, and that the observed bands could easily be
      assigned on the basis of these calculations. Achieving this level of accuracy in
      the simulations at modest computational cost should now allow computational
      methods to be combined with experimental Raman studies much more widely than is
      currently the case.

PMID- 15584076
TI  - Low-melting, low-viscous, hydrophobic ionic liquids: aliphatic quaternary
      ammonium salts with perfluoroalkyltrifluoroborates.
AB  - A novel class of low-melting, hydrophobic ionic liquids based on relatively small
      aliphatic quaternary ammonium cations ([R(1)R(2)R(3)NR](+), wherein R(1), R(2),
      R(3) = CH(3) or C(2)H(5), R = n-C(3)H(7), n-C(4)H(9), CH(2)CH(2)OCH(3)) and
      perfluoroalkyltrifluoroborate anions ([R(F)BF(3)](-), R(F) = CF(3), C(2)F(5), n
      C(3)F(7), n-C(4)F(9)) have been prepared and characterized. The important
      physicochemical and electrochemical properties of these salts, including melting
      point, glass transition, viscosity, density, ionic conductivity, thermal and
      electrochemical stability, have been determined and comparatively studied with
      those based on the corresponding [BF(4)](-) and [(CF(3)SO(2))(2)N](-) salts. The
      influence of the structure variation in the quaternary ammonium cation and
      perfluoroalkyltrifluoroborate ([R(F)BF(3)](-)) anion on the above physicochemical
      properties is discussed. Most of these salts are liquids at 25 degrees C and
      exhibit low viscosities (58-210 cP at 25 degrees C) and moderate conductivities
      (1.1-3.8 mS cm(-1)). The electrochemical windows of these salts are much larger
      than those of the corresponding 1,3-dialkyimidazolium salts. Additionally, a
      number of [R(F)BF(3)](-) salts exhibit plastic crystal behavior.

PMID- 15584077
TI  - Ab initio study of the complexes of halogen-containing molecules RX (X=Cl, Br,
      and I) and NH3: towards understanding the nature of halogen bonding and the
      electron-accepting propensities of covalently bonded halogen atoms.
AB  - Ab initio calculations have been performed on a series of complexes formed
      between halogen-containing molecules and ammonia to gain a deeper insight into
      the nature of halogen bonding. It appears that the dihalogen molecules form the
      strongest halogen-bonded complexes with ammonia, followed by HOX; the charge
      transfer-type contribution has been demonstrated to dominate the halogen bonding
      in these complexes. For the complexes involving carbon-bound halogen molecules,
      our calculations clearly indicate that electrostatic interactions are mainly
      responsible for their binding energies. Whereas the halogen-bond strength is
      significantly enhanced by progressive fluorine substitution, the substitution of
      a hydrogen atom by a methyl group in the CH(3)X...NH(3) complex weakened the
      halogen bonding. Moreover, remote substituent effects have also been noted in the
      complexes of halobenzenes with different para substituents. The influence of the
      hybridization state of the carbon atom bonded to the halogen atom has also been
      examined and the results reveal that halogen-bond strengths decrease in the order
      HC triple bond CX > H(2)C=CHX approximately O=CHX approximately C(6)H(5)X >
      CH(3)X. In addition, several excellent linear correlations have been established
      between the interaction energies and both the amount of charge transfer and the
      electrostatic potentials corresponding to an electron density of 0.002 au along
      the R-X axis; these correlations provide good models with which to evaluate the
      electron-accepting abilities of the covalently bonded halogen atoms. Finally,
      some positively charged halogen-bonded systems have been investigated and the
      effect of the charge has been discussed.

PMID- 15584078
TI  - Aldol condensations over reconstructed Mg-Al hydrotalcites: structure-activity
      relationships related to the rehydration method.
AB  - Two different rehydration procedures in the liquid or gas phase have been applied
      to reconstruct mixed oxides derived from calcined hydrotalcite-like materials to
      be used as catalysts for aldol condensation reactions. The as-synthesized
      hydrotalcite, its decomposition product, as well as the reconstructed solids upon
      rehydration were characterized by XRD, N(2) adsorption, He pycnometry, FTIR, SEM,
      TEM, (27)Al MAS-NMR and CO(2)-TPD (TPD=temperature-programmed desorption).
      Compared to the Mg-Al mixed oxide rehydrated in the gas phase (HT-rg), that
      rehydrated in the liquid phase (HT-rl) exhibits a superior catalytic performance
      with respect to the aldol condensation of citral with ketones to yield
      pseudoionones and in the self-aldolization of acetone. The textural properties of
      HT-rl and HT-rg differ strongly and determine the catalytic behavior. A memory
      effect led to a higher degree of reconstruction of the lamellar structure when
      the mixed oxide was rehydrated in the gas phase rather than in the liquid phase,
      although liquid-phase rehydration under fast stirring produced a surface area
      that was 26 times greater. This contrasts to typical statements in the literature
      claiming a higher degree of reconstruction in the presence of large amounts of
      water in the medium. CO(2)-TPD shows that the number of OH(-) groups and their
      nature are very similar in HT-rg and HT-rl, and cannot explain the markedly
      different catalytic behavior. Accordingly, only a small fraction of the available
      basic sites in the rehydrated samples is active in liquid-phase aldol
      condensations. Our results support the model in which only basic sites near the
      edges of the hydrotalcite platelets are partaking in aldol reactions. Based on
      this, reconstructed materials with small crystallites (produced by exfoliation
      during mechanical stirring), that is, possessing a high external surface area,
      are beneficial in the reactions compared to larger crystals with a high degree of
      intraplatelet porosity.

PMID- 15584079
TI  - Evolutionary method for the assembly of rigid protein fragments.
AB  - Genetic algorithms constitute a powerful optimization method that has already
      been used in the study of the protein folding problem. However, they often suffer
      from a lack of convergence in a reasonably short time for complex fitness
      functions. Here, we propose an evolutionary strategy that can reproducibly find
      structures close to the minimum of a potential function for a simplified protein
      model in an efficient way. The model reduces the number of degrees of freedom of
      the system by treating the protein structure as composed of rigid fragments. The
      search incorporates a double encoding procedure and a merging operation from
      subpopulations that evolve independently of one another, both contributing to the
      good performance of the full algorithm. We have tested it with protein structures
      of different degrees of complexity, and present our conclusions related to its
      possible application as an efficient tool for the analysis of folding potentials.

PMID- 15584080
TI  - Incorporating the effect of ionic strength in free energy calculations using
      explicit ions.
AB  - The incorporation of explicit ions to mimic the effect of ionic strength or to
      neutralize the overall charge on a system in free energy calculations using
      molecular dynamics simulations is investigated. The difference in the free energy
      of hydration between two triosephosphate isomerase inhibitors calculated at five
      different ion concentrations is used as an example. We show that the free energy
      difference can be highly sensitive to the presence of explicit ions even in cases
      where the mutation itself does not involve a change in the overall charge. The
      effect is most significant if the molecule carries a net charge close to the site
      mutated. Furthermore, it is shown that the introduction of a small number of ions
      can lead to very severe sampling problems suggesting that in practical
      calculations convergence can best be achieved by incorporating either no
      counterions or by simulating at high ionic strength to ensure sufficient sampling
      of the ion distribution.

PMID- 15584081
TI  - DommiMOE: an implementation of ligand field molecular mechanics in the molecular
      operating environment.
AB  - The ligand field molecular mechanics (LFMM) model, which incorporates the ligand
      field stabilization energy (LFSE) directly into the potential energy expression
      of molecular mechanics (MM), has been implemented in the "chemically aware"
      molecular operating environment (MOE) software package. The new program,
      christened DommiMOE, is derived from our original in-house code that has been
      linked to MOE via its applications programming interface and a number of other
      routines written in MOE's native scientific vector language (SVL). DommiMOE
      automates the assignment of atom types and their associated parameters and
      popular force fields available in MOE such as MMFF94, AMBER, and CHARMM can be
      easily extended to provide a transition metal simulation capability. Some of the
      unique features of the LFMM are illustrated using MMFF94 and some simple [MCl)]2-
      and [Ni(NH3)n]2+ species. These studies also demonstrate how density functional
      theory calculations, especially on experimentally inaccessible systems, provide
      important data for designing improved LFMM parameters. DommiMOE treats Jahn
      Teller distortions automatically, and can compute the relative energies of
      different spin states for Ni(II) complexes using a single set of LFMM parameters.

PMID- 15584083
TI  - Simultaneous determination of beta-blocking agents and diuretics in doping
      analysis by liquid chromatography/mass spectrometry with scan-to-scan polarity
      switching.
AB  - A previously described method for the screening of 18 diuretics and probenecid
      was substantially extended with 21 beta-blockers and 8 other diuretics allowing
      simultaneous determination of diuretics and beta-adrenergic blocking agents in
      human urine. Analysis was performed using an ion trap instrument with an
      electrospray ionisation (ESI) interface after liquid/liquid extraction with ethyl
      acetate. Full-scan MS and full-scan MS2 were applied in combination with scan-to
      scan polarity switching. All compounds were separated in less than 22 min. The
      detection limits for the diuretics were between 5 and 100 ng/mL and for the beta
      adrenergic blocking agents were between 5 and 500 ng/mL. The excretion of
      carvedilol was followed after intake of one tablet of Dimitone. Other doping
      agents including strychnine, norbuprenorphine and mesocarb hydroxysulfate could
      also be detected with this method.

PMID- 15584084
TI  - The analysis of high explosives by liquid chromatography/electrospray ionization
      mass spectrometry: multiplexed detection of negative ion adducts.
AB  - The negative ion electrospray ionization mass spectrometric (ESI-MS) detection of
      adducts of high explosives with chloride, formate, acetate, and nitrate was used
      to demonstrate the gas-phase interaction of neutral explosives with these anions.
      The relative intensities of the adduct species were determined to compare the
      competitive formation of the selected high explosives and anions. The relative
      stability of the adduct species varies, yielding preferential formation of
      certain anionic adducts with different high explosives. To exploit this effect,
      an isocratic high-performance liquid chromatography (HPLC)/ESI-MS method was
      developed and used for the simultaneous analysis of high explosives using two
      different techniques for the addition of the anionic additives; pre- and post
      column. The results show that the pre-column approach provides similar results
      with improved selectivity for specific explosives. By detecting characteristic
      adduct species for each explosive, this method provides a qualitative and
      quantitative approach for the analysis and identification of high explosives.

PMID- 15584086
TI  - Gas chromatography/ion trap mass spectrometry applied for the determination of
      polybrominated diphenyl ethers in soil.
AB  - A gas chromatography/ion trap mass spectrometry (GC/ITMS) method was developed
      for the determination of polybrominated diphenyl ethers (PBDEs). ITMS parameters
      were optimized in order to achieve the best sensitivity for the PBDE analysis.
      Tandem mass spectrometry, along with an isotope dilution internal standard
      method, was used for the quantitation. Chromatographic windows were developed for
      mono- to hepta-BDEs, depending on the retention times when a 30-m GC column was
      used. A different 15-m column was used to analyze deca-BDE. Environmental soil
      samples collected from an electronic waste recycling site were prepared by using
      Soxhlet extraction and column chromatographic cleanup. Average recoveries of 61
      118% were obtained for the 13C-labeled PBDE internal standards spiked in the
      samples prior to sample preparation. The accuracy represented by relative
      analytical errors was -24% to 18%, and the precision (relative standard
      deviation) was 11-26% (n=8). The method detection limits ranged from 0.013-0.25
      ng/g for the PBDEs in soil.

PMID- 15584087
TI  - The myofibroblast, cadherin, alpha smooth muscle actin and the collagen effect.
AB  - In granulation tissue the myofibroblast, a specialized fibroblast characterized
      by cytoplasmic stress fibres with alpha smooth muscle actin (SMA), develops from
      mechano-tension between cells. In vitro the myofibroblast phenotype can be
      induced in the absence of obvious tension by plating human dermal fibroblasts at
      low density (LD). Upon reaching confluence the LD-plated cells express alpha SMA
      within stress fibres. In contrast, few cells express alpha SMA when those same
      fibroblasts are plated at high density (HD). Cadherins, trans-membrane proteins,
      and link cells tie the cytoskeletal stress fibres of neighbouring cells together.
      By immunohistology myofibroblasts (LD-plated fibroblasts) are shown to express
      cadherin-11 on their surface and between cells, while HD-plated fibroblasts
      expressed less cadherin-11 on their surface. Western blot analysis revealed
      elevated concentrations of cadherin-11 and alpha SMA in confluent LD-plated cell
      lysates. Reduced amounts of both proteins were found in confluent HD-plated cell
      lysates. Plating fibroblasts on collagen inhibits alpha SMA synthesis. When
      confluent LD-plated myofibroblasts were covered with a collagen lattice for 24 h,
      both the expression of cadherin-11 and alpha SMA were reduced by 50%. There is
      the possibility that direct linkage of the cytoskeleton stress fibres by cell
      surface cadherins maintains tension between neighbouring cells, which induces
      alpha SMA expression in stress fibres. Cell contact with collagen reduces
      cadherin expression, which may eliminate the generation of mechano-tension
      between fibroblasts. The other possibility is that the myofibroblast phenotype
      may be induced by factors other than mechano-tension.

PMID- 15584088
TI  - Cyclosporin-A inhibits stretch-induced changes in myosin heavy chain expression
      in C2C12 skeletal muscle cells.
AB  - Studies in vivo, have shown that passive stretch of skeletal muscle induces
      changes in contractile protein expression. In the present study the effects of
      passive stretch upon myosin heavy chain (MyHC) expression were examined in C2C12
      cell myotubes. Passive stretch induced an upregulation of adult fast and slow
      MyHCs, which was prevented by cyclosporin A (CsA), an inhibitor of calcineurin.
      Calcineurin has been shown to act via the dephosphorylation of NFAT and MEF2
      transcriptional factors. In this study no significant change in the
      phosphorylation state of these factors was observed. In contrast stretch induced
      an alteration in the levels of the myogenic regulatory factors (MRFs) MyoD,
      myogenin and myf5. The modulation in the level of these MRFs was also inhibited
      by CsA. These data indicate that changes in muscle phenotype in C2C12 can be
      modulated by passive stretch and some of these changes are calcineurin dependent.

PMID- 15584089
TI  - Transient transfection of epidermal growth factor receptor gene into MCF7 breast
      ductal carcinoma cell line.
AB  - Epidermal growth factor receptor (EGFR) is activated by autocrine growth factors
      in many types of tumours, including breast tumours. This receptor has been linked
      to a poor prognosis in breast cancer and may promote proliferation, migration,
      invasion, and cell survival as well as inhibition of apoptosis. Human breast
      ductal carcinoma MCF7 cells were transfected using FuGENE 6 with 1 microg of
      pcDNA3-EGFR containing the full-length human EGFR promoter or 1 microg of the
      vectors alone (pcDNA3). The transfected cells were transferred into a 25-cm2
      flask containing growth medium and G418. Confluent cultures were lysed, total
      protein levels measured and electrophoresed. The electrophoresed samples were
      transferred to nitrocellulose and incubated overnight at 4 degrees C with either
      anti-EGFR or anti-phospho-ERK and immunoreactive bands were visualized using HRP
      linked secondary antibody. We created a model system of EGFR overexpression in
      MCF7 clones with stably transfected pcDNA3/EGFR plasmid. These cells have been
      shown to promote substantial phosphorylation of both ERK1 and ERK2. The high
      level of EGFR and ERK1/2 phosphorylation was not seen in the pcDNA3 vector
      control cells or in non-transfected cells. In this article we describe successful
      transient transfection experiments on MCF7 cells using the FuGENE 6 Transfection
      Reagent. The overexpression of EGFR could be a mediated stress response and a
      survival signal that involves ERK1 and ERK2 phosphorylation.

PMID- 15584090
TI  - Biochemical and genetic characterization of Yra1p in budding yeast.
AB  - Yra1p and its vertebrate homologues bind to the mRNA export factor Mex67p/TAP and
      are thought to play a role in mRNA export in vivo. To further characterize Yra1p,
      we used immunoaffinity chromatography to purify endogenous Yra1p complexes. These
      experiments demonstrated that two importin beta homologues (Kap123p and Pse1p)
      and the poly A tail-binding proteins Pab1p and Nab2p associate with Yra1p. The
      other major proteins that associate with Yra1p include proteins involved in mRNA
      and rRNA processing and the Yra1p-related protein Yra2p. Additional biochemical
      and genetic experiments suggest a close functional relationship between Yra1p and
      Yra2p. We generated a temperature-sensitive allele of YRA1 and used it to
      demonstrate that cells which lack the function of both Yra1p and Yra2p are able
      to exit a G0 arrest and go through several rounds of cell division before
      arresting. We also identified high-copy suppressors of the yra1-2 temperature
      sensitive growth defect. These include SUB2, a splicing factor important in mRNA
      export, ULP1, a nuclear cysteine protease localized to the nuclear pore and
      involved in Smt3p/SUMO processing, and YRA2. Taken together, these results
      suggest that Yra1p has roles in diverse RNA processing events in addition to a
      role in mRNA export.

PMID- 15584091
TI  - Protective effect of chelerythrine on gentamicin-induced nephrotoxicity.
AB  - Despite their beneficial effects, aminoglycosides including gentamicin (GEN) have
      considerable nephrotoxic side-effects. The toxicity of GEN at the level of the
      kidney seems to relate to the generation of reactive oxygen species (ROS). ROS
      have been reported to be involved in the activation of protein kinase C (PKC).
      The unique structural aspects of PKC cause it to function as a sensor for
      oxidative stress. It seems likely that the increased NAD(P)H oxidase-derived
      superoxide (O2) production is at least in part mediated by PKC. We investigated
      the effects of chelerythrine, a commonly used PKC inhibitor, on GEN-induced
      changes of renal malondialdehyde (MDA), nitric oxide (NO) generation, catalase
      (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities,
      glutathione (GSH) content, and serum creatinine (Cr), blood urea nitrogen (BUN)
      levels. Morphological changes in the kidney were also examined. GEN
      administration to control rats increased MDA and NO generation but decreased CAT,
      SOD and GSH-Px activities, and GSH content. Chelerythrine administration with GEN
      caused significantly decreased MDA, NO generation and increased CAT, SOD and GSH
      Px activities, and GSH content when compared with GEN alone. Chelerythrine also
      significantly decreased serum Cr and BUN levels. Morphological changes in the
      kidney including tubular necrosis were evaluated qualitatively. Both biochemical
      findings and histopathological evidence showed that administration of
      chelerythrine reduced the GEN-induced kidney damage. We propose that
      chelerythrine acts in the kidney as a potent scavenger of free radicals to
      prevent the toxic effects of GEN via the inhibition of a PKC pathway.

PMID- 15584092
TI  - Acute and delayed effect of (-) deprenyl and (-) 1-phenyl-2-propylaminopentane
      (PPAP) on the serotonin content of peritoneal cells (white blood cells and mast
      cells).
AB  - Acute and delayed (hormonal imprinting) effect of (-) deprenyl and its derivative
      without MAO-B inhibitory activity (-) PPAP, were studied on cells of the
      peritoneal fluid (lymphocytes, monocytes, granulocytes and mast cells) by flow
      cytometric and confocal microscopic analysis. Thirty minutes after treatment of 6
      week-old female animals, deprenyl was ineffective while PPAP significantly
      increased the serotonin level of these cells. Three weeks after treatment at
      weaning, deprenyl drastically decreased the serotonin level of each cell type,
      while PPAP moderately but significantly increased the serotonin level of
      monocytes, granulocytes and mast cells. This means that the two related molecules
      have different effects on the immune cells, which seem to be independent of MAO-B
      inhibition. The experiments emphasize the necessity of studying the prolonged
      effects of biologically active molecules, even if they are without acute effects.
      As serotonin is a modulator of the immune system, the influence on immune cells
      of the molecules studied can contribute to their enhancing effect.

PMID- 15584093
TI  - Electrical stimulation modulates IGF binding protein transcript levels in C2C12
      myotubes.
AB  - Electrical stimulation (ES) of skeletal muscle can produce changes in metabolic
      enzyme and contractile protein gene expression resulting in fast-to-slow
      phenotypic changes. The molecular mechanism by which ES induces changes in
      phenotype is not entirely understood but recent reports have demonstrated that
      the calcineurin/NF-AT signalling pathway is involved. IGF-1 is also capable of
      inducing changes in phenotype through the same calcineurin/NF-AT pathway but
      little is known of the direct effect of ES on the IGF system. In this study, we
      examined the effects of ES on the expression of igf-1, igf-2 and the six igfbp
      genes in the C2C12 muscle cell line. Results showed that ES induced a change in
      phenotype that was accompanied by downregulation of igf-2 and upregulation of
      igfbp-4 mRNA levels. However, ES did not significantly alter the transcription of
      igf-1, igfbp-2, igfbp-5 and igfbp-6 genes. This study demonstrates that ES of
      muscle cells in vitro not only directly modulates the gene expression of
      contractile proteins but also modulates proteins that are part of the IGF
      regulatory system, in particular IGFBP-4.

PMID- 15584094
TI  - Dose-dependent effects of carbendazim on rat thymus.
AB  - In this study, the effects of carbendazim on the thymus in male rats were
      evaluated. Carbendazim was administered at 0, 150, 300 and 600 mg kg(-1) day(-1)
      doses by gavage to male rats for 15 weeks. Body weights of rats in all groups
      were recorded weekly during treatment. At the end of the experiment, the effects
      of carbendazim on the thymus were investigated histopathologically and
      morphologically. Also, based on these effects, change in immunolocalization of
      fibronectin (FN), which is a component of the extracellular matrix, was
      investigated immunohistochemically. Fibrosis and oedema were observed in the
      thymus of rats treated with 300 and 600 mg kg(-1) day(-1) doses of carbendazim.
      Also in this region, an increase in FN density was noted at the end of the
      immunohistochemical investigation. A decrease was observed in absolute and
      relative thymus weights of rats treated with carbendazim compared with the
      control group. While the decrease in absolute thymus weight was statistically
      significant in rats exposed to carbendazim at the highest dose, the decrease in
      relative thymus weights was statistically significant for all carbendazim doses.

PMID- 15584095
TI  - Palaeoclimatology: Archaean atmosphere and climate.
AB  - Ohmoto et al. argue that carbon dioxide was abundant in the late Archaean and
      early Proterozoic atmosphere and that methane was probably scarce, based on a
      reanalysis of the occurrence of siderite, FeCO3, in ancient rocks. Here I
      consider several factors that may undermine their conclusions.

PMID- 15584096
TI  - Palaeoclimatology: Archaean palaeosols and Archaean air.
AB  - Ferrous carbonate, as the mineral siderite, occurs in Archaean palaeosols
      (ancient soils). Ohmoto et al. contend that siderite was not in equilibrium with
      the oxygen in Archaean air and that its presence in palaeosols provides little
      constraint on the partial pressure of carbon dioxide in Archaean air. But their
      argument is invalid because it fails to distinguish the different behaviours of
      the trivial component oxygen and the significant component carbon dioxide in the
      partly closed system of soil waters. The presence or absence of siderite in
      ancient soils is a valid constraint on the carbon dioxide partial pressure (pCO2)
      in ancient atmospheres.

PMID- 15584097
TI  - Atmospheric science: tropospheric temperature series from satellites.
AB  - There has been considerable debate about changes in the temperature of the
      troposphere measured using the Microwave Sounding Unit (MSU) instrument or
      radiosondes. Fu et al. linearly combine time series from two MSU channels to
      estimate vertically integrated 850-300-hPa temperatures and claim consistency
      between surface and free-troposphere warming for one MSU record. We believe that
      their approach overfits the data, produces trends that overestimate warming and
      gives overly optimistic uncertainty estimates. There still remain large
      differences between observed tropospheric temperature trends and those simulated
      by a climate model.

PMID- 15584098
TI  - Atmospheric science: stratospheric cooling and the troposphere.
AB  - Satellite observations of tropospheric temperatures seem to show less warming
      than surface temperatures, contrary to physical predictions. Fu et al. show that
      statistical correction for the effect of stratospheric cooling brings the
      satellite-based estimates of tropospheric warming into closer agreement with
      observations of surface warming. Here we apply the method of Fu et al. to output
      from a state-of-the-art coupled climate model and show that simulated
      tropospheric temperature trends are consistent with those observed and that their
      method is robust.

PMID- 15584099
TI  - Consolidation and the transformation of competition in health insurance.
AB  - This paper presents data on fifty state and substate insurance markets, in terms
      of the 2003 relative shares of the largest health plans and the antitrust index
      of concentration. It presents 2000-03 data on rates of growth in premiums, costs,
      operating earnings, returns on equity, and share prices for the nation's largest
      health plans (Well-Point, Anthem, Aetna, and CIGNA). Private insurers face
      renewed price and profit pressures in the short term, but long-term prospects
      depend on the emergence of new products and new competitors in an increasingly
      consolidated industry.

PMID- 15584100
TI  - Can disease management reduce health care costs by improving quality?
AB  - Disease management (DM) promises to achieve cost savings by improving the quality
      of care for chronic diseases. During the past decade the Permanente Medical Group
      in Northern California has implemented extensive DM programs. Examining quality
      indicators, utilization, and costs for 1996-2002 for adults with four conditions,
      we find evidence of substantial quality improvement but not cost savings. The
      causal pathway--from improved care to reduced morbidity to cost savings--has not
      produced sufficient savings to offset the rising costs of improved care. We
      conclude that the rationale for DM programs, like the rationale for any medical
      treatments, should rest on their effectiveness and value.

PMID- 15584101
TI  - The role of the individual health insurance market and prospects for change.
AB  - The individual market is the only source of health insurance for the more than 20
      percent of Americans not eligible for group or public health insurance; yet
      participation rates are low and shrinking. This paper examines this market's
      structural features and assesses the likelihood that it will play an expanded
      role in the future. We describe how pressures such as cost growth, new
      technologies, and changes in the nature of the workplace are shaping the
      individual market. We conclude that the future of the market will depend largely
      on whether there are policy interventions that balance the problems of
      affordability, risk sharing, and adverse selection.

PMID- 15584102
TI  - As the health insurance underwriting cycle turns: what next?
AB  - After twenty-five years of a consistent health insurance underwriting cycle, the
      pattern of insurer profitability changed greatly in the 1990s, raising
      speculation about the future. We conclude from interviews with industry experts
      that health plan competition and limits on plans' ability to predict costs will
      continue to drive a cycle, albeit one even more muted than it was in the 1990s
      because of changes in industry structure and forecasting improvements. Plans will
      price closer to cost trends and forego the more heated price competition that
      drove major losses in the past, reducing premium volatility but possibly leading
      to higher average premiums.

PMID- 15584103
TI  - Consumer-directed health plans and the RAND Health Insurance Experiment.
AB  - Today's consumer-directed health plans, with their high deductibles, bear a
      strong resemblance to the high-deductible plan of the RAND Health Insurance
      Experiment (HIE), although they come into a post-managed-care world. The high
      deductibles and the tools of managed care should complement each other, the
      former directed primarily at the initiation of care for an episode of illness and
      the latter at the costliness of episodes, especially ongoing chronic disease
      episodes. Although the RAND experiment established the effects of varying prices
      to patients, future experiments with how physicians respond to the various tools
      of managed care may be useful.

PMID- 15584104
TI  - Business opportunities in transforming health care: an interview with William W.
      McGuire.
AB  - After a spate of high-profile acquisitions including Oxford Health Plans,
      UnitedHealth Group (UHG) covers twenty-two million Americans in insured and self
      insured health plans and tens of millions more through specialty products. Bill
      McGuire describes his strategy of growth through acquisition and through
      diversification into Medicaid managed care, the individual insurance market, and
      services for the elderly under the Medicare Modernization Act of 2003. He sees
      business and public policy opportunities in the unjustifiable variation in cost
      and quality across the health care spectrum and proposes a framework of basic
      insurance benefits for all Americans, with options for people to purchase
      additional benefits with their own money.

PMID- 15584105
TI  - Historical keywords: bioethics.

PMID- 15584106
TI  - Arthritis drug raises risk of sudden heart attack.

PMID- 15584107
TI  - Mediterranean diet linked to lower markers of heart disease.

PMID- 15584108
TI  - Mechanism in stroke causes brain cells to starve.

PMID- 15584109
TI  - When PSA levels are dangerous. Comparing baseline PSA with follow-up scores is
      critical to determining risk and severity of prostate cancer.

PMID- 15584110
TI  - Infection fatal in many with cancer. Better prevention and treatment of severe
      sepsis could increase overall cancer survival.

PMID- 15584111
TI  - New drugs reduce risk of death from breast cancer.

PMID- 15584112
TI  - Drug improves survival for advanced colon cancer.

PMID- 15584113
TI  - Long-term relief for RA? Potential therapy targets cells that, in rheumatoid
      arthritis, short circuit and attack the body.

PMID- 15584114
TI  - How low should your cholesterol go? Even lower may be better. For those at
      highest risk, very low cholesterol levels may help prevent a second heart attack
      or stroke.

PMID- 15584115
TI  - Can calcium in your coronary arteries portend a heart attack? This marker can
      help your doctor prescribe the right medication, but it's really just another
      risk factor.

PMID- 15584116
TI  - The power of blueberries and...red beans, pecans and artichokes--they all have
      one thing in common: they all rank among the top 20 food high in beta carotene
      and vitamins C and E.

PMID- 15584117
TI  - 10,000 steps toward good health. Counting the number of steps you take is a great
      motivational tool that provides immediate feedback.

PMID- 15584118
TI  - Depression and the fading brain. Older adults suffering from depression are
      likely to experience dementia.

PMID- 15584119
TI  - Common Alzheimer's drug flunks test of effectiveness. Initial improvements in
      cognitive ability made by cholinesterase inhibitors soon disappear.

PMID- 15584121
TI  - Help for dry eyes and mouth. A simple test for tear production can lead to early
      diagnosis, the key to treating Sjogren Syndrome.

PMID- 15584120
TI  - Rx for remembering medications: imagination.

PMID- 15584122
TI  - Worried about traveler's diarrhea?

PMID- 15584123
TI  - Soy no panacea for postmenopausal women.

PMID- 15584124
TI  - Scar-free surgery.

PMID- 15584125
TI  - Relief for pain of neuropathy. The anticonvulsant drug topiramate targets the
      underlying disease of diabetics.

PMID- 15584126
TI  - ACE inhibitors reduce heart-related death in type 2 diabetics.

PMID- 15584127
TI  - Blood test may measure women's iron levels to predict diabetes risk.

PMID- 15584128
TI  - Human and economic toll of diabetes increased.

PMID- 15584129
TI  - I'm 75 and have heard about the flu patch under investigation. What can you tell
      me about it, and is my only option for flu vaccination a shot?

PMID- 15584130
TI  - I have osteoarthritis in both of my knees. What drugs are available for treatment
      options?

PMID- 15584131
TI  - Imaging the addicted brain: from molecules to behavior.

PMID- 15584132
TI  - ECTRIMS 04. Abstracts of the 20th Congress of the European Committee for
      Treatment and Research in Multiple Sclerosis and the 9th Annual Meeting of
      Rehabilitation in Multiple Sclerosis. October 6-9, 2004, Vienna, Austria.

PMID- 15584133
TI  - Abstracts of the XXI Brazilian Congress of Neurology, 9-14 October 2004.

PMID- 15584134
TI  - Orthopaedic proceedings: 2001, 2003.

PMID- 15584135
TI  - 5-HT3 receptor antagonists: a new therapeutic approach in rheumatology?
      Proceedings of a symposium. Frankfurt, Germany, February 12-13, 2004.

PMID- 15584136
TI  - Blackman v. New York City Health and Hospitals Corporation.

PMID- 15584137
TI  - New internal radiation dose and modeling software; FDA approves commercial
      MIRDOSE successor.

PMID- 15584138
TI  - Howell honored with Loevinger-Berman Award.

PMID- 15584139
TI  - Rhode Island Medical Society v. Whitehouse.

PMID- 15584140
TI  - HIV dementia mechanism assessed.

PMID- 15584142
TI  - Antibiotic-associated diarrhea: it's all about the butyrate.

PMID- 15584141
TI  - Direct detection of Shiga toxin: a necessary step for improved diagnosis of
      enterohemorrhagic colitis.

PMID- 15584143
TI  - Conflicting perceptions of the fetus: person, patient, 'nobody', commodity?
AB  - Different constructions of the fetus lie at the centre of reproductive, abortion
      and disability politics. Recent developments mean that, within the same hospital,
      a fetus may be perceived in contrasting and potentially conflicting ways. It is
      also argued that the status given to the fetus is directly relevant to the status
      given to pregnant women. During group discussions facilitated by an ethicist,
      health-care staff highlighted various perceptions of the fetus which included:
      person; patient; 'nobody'; commodity. Perhaps not surprisingly in view of the
      current legal situation, staff tended to claim that it is usually the pregnant
      women who decides how her fetus will be constructed, and the practitioner who
      responds to this. However, various ways in which practitioners might influence
      women's perceptions of their fetus are highlighted, as are some ways in which the
      perceptions of staff might be influenced. This paper illustrates how sensitive
      health-care staff will need to be if they are indeed to respond to, rather than
      shape, women's constructions of their fetus.

PMID- 15584144
TI  - Religion and the public discourse of bioethics.

PMID- 15584145
TI  - A dispute in withdrawing life-sustaining therapy.

PMID- 15584146
TI  - Schrodinger's cat, eugenics, and the compulsory sterilization of welfare mothers:
      deconstructing an old/new rhetoric and constructing the reproductive right to
      natality for low-income women of color.

PMID- 15584147
TI  - Proceedings of the 16th IRIST Congress 2003: Peptide Radiopharmaceuticals in
      Diagnosis and Therapy of Cancer and Inflammation/Infection. May 8-10, 2003, Isle
      of Capri, Italy.

PMID- 15584148
TI  - Researching ethically with human subjects in cyberspace.

PMID- 15584149
TI  - Swedish standards set for use of genetic 'biobanks'.

PMID- 15584151
TI  - Symposium Mammographicum 2004. Edinburgh, UK, 19-20 July 2004. Abstracts.

PMID- 15584150
TI  - Judicial decisionmaking in the age of biotechnology.

PMID- 15584152
TI  - Dose response: intelligent rationing by physicians is the first step to a health
      care system that society can afford.

PMID- 15584153
TI  - World Medical Association Declaration on Principles of Health Care for Sports
      Medicine.

PMID- 15584154
TI  - Monitoring of approved research by a Scottish LREC: two questionnaires.

PMID- 15584155
TI  - Safeguarding informed parental involvement in clinical research involving newborn
      babies and infants.

PMID- 15584157
TI  - Bibliography of toxinology.

PMID- 15584156
TI  - Do doctors know the content of the Hippocratic Oath and other medical oaths and
      declarations?

PMID- 15584158
TI  - Medical Research Act 1999 (Finland).

PMID- 15584159
TI  - Abstracts and proceedings from the 3rd Research Meeting on Melanoma for
      dermatologists, surgeons, medical and experimental oncologists. Milan, Italy, May
      26-27, 2003.

PMID- 15584160
TI  - Observations from six years' experience of a health and safety research ethics
      committee.
AB  - The work of the Health and Safety Executive Research Ethics Committee is
      presented in the light of 100 studies submitted for consideration over its first
      six years of operation. Ethical issues which have arisen in the context of this
      non-therapeutic research, and which are considered by the committee to be of
      particular importance are highlighted and exemplified by specific case studies.

PMID- 15584161
TI  - No rush to death: the Dutch are famously tolerant of euthanasia. But they don't
      do much of it.

PMID- 15584162
TI  - An ethical problem for discussion, in transplantation research.

PMID- 15584163
TI  - Clinical trials in Uganda.

PMID- 15584164
TI  - Using Ugandans for American research.

PMID- 15584165
TI  - Proposed ethical guidelines for genetic engineering.

PMID- 15584166
TI  - Is it possible to take both fetal life and women seriously? Professor Laurence
      Tribe and his reviewers.

PMID- 15584167
TI  - Bioethical dilemmas: decision-making and the Human Genome Project.

PMID- 15584168
TI  - Implantable brain chips: ethical and policy issues.

PMID- 15584169
TI  - The patient in the middle--when perspectives differ.

PMID- 15584170
TI  - [Paul Konitzer (1894-1947): hygienist, physician, social medicine and health
      politician].
AB  - Paul Konitzer was one of the outstanding and well-known physicians in the years
      after the World War II in East-Germany. THe paper describes his professional way
      as hygienist, social medical, municipal physician and last but not least as
      health politician in the times of four different political regimes: the imperial
      era in Germany till 1918, the time of "Weimarer Republic" till 1933, the Nazi
      dictatorship till 1945 and the early years in the Soviet occupation zone of
      Germany. The life of Konitzer is a typical example of the fate of a German doctor
      in the first half of the 20th century. Konitzer was arrested in February 1947 by
      the Soviet Military Government in Berlin in connection with some political
      troubles and reproach with a typhus epidemic in a German camp for Russian
      Prisoners of War in the Nazi era. On April 22nd 1947 he died in prison of Dresden
      by suicide without condemnation.

PMID- 15584171
TI  - The women radium dial painters as experimental subjects (1920-1990) or what
      counts as human experimentation.
AB  - The case of women radium dial painters - women who tipped their brushes while
      painting the dials of watches and instruments with radioactive paint - has been
      extensively discussed in the medical and historical literature. Their painful and
      abhorrent deaths have occupied the interest of physicians, lawyers, politicians,
      military agencies, and the public. Hardly any discussion has concerned, however,
      the use of those women as experimental subjects in a number of epidemiological
      studies that took place from 1920 to 1990. This article addresses the neglected
      issue of human experimentation in relation to the radium dial painters. Although
      women's medical examinations have been classified as simple, routine measurements
      of radiation burden on the body and presented as a great offer to humanity, for
      more than fifty years those women had been repeatedly used as experimental
      subjects without proper consent. I argue that through this case it becomes
      obvious that the issue of defining what counts as human experimentation shifts
      from an epistemological to a serious ethical and political question, concerning
      the making of scientific knowledge while issues of gender related to this process
      are also discussed.

PMID- 15584172
TI  - [Medical technologies in the contemporary world: an historical approach from the
      peripheries. Introduction].

PMID- 15584173
TI  - [Giving birth to medical instruments: forceps and pelvimeters among obstetricians
      of the 19th century in Mexico].
AB  - Up until the mid-19th century, Mexican obstetricians associated forceps and other
      surgical instruments with risky operations, considering them artefacts whose use
      was to be avoided at all cost. This article asks why by the century's end these
      same instruments had come to be seen as life-saving surgical utensils. To this
      end, I analyzed clinical narratives that defined the norms and practices of their
      use, discovering that although forceps were redefined by male-midwives' norms of
      prudence, they also introduced medically-based ideas of gender and race and
      attributed to Mexican women's pelvises a supposedly pathological nature.

PMID- 15584174
TI  - [Woman or man? Hermaphroditism, medical technologies and sex identification in
      Spain, 1860-1925].
AB  - This article makes a contribution to recent medical historiography on the subject
      of the historical category of sex. By means of a detailed study of medical
      accounts published in Spain between 1860 and 1925 we analyse knowledge on the
      question of the identification of sex, male or female, with reference to the
      borderline category of "hermaphroditism". The technologies utilised by medico
      legal sources to determine sex and the complex network of elements involved in
      establishing the biological dichotomy between men and women are prominent in our
      discussion.

PMID- 15584175
TI  - The introduction of diagnostic and treatment innovations for syphilis in post-war
      VD policy: "L'experience belge".
AB  - In this article, the introduction of the Wassermann Test and arsenic-based drugs
      in Belgian post-war venereal disease (VD) policy is discussed (for the period of
      1900-1930). Pre-war advances in clinical medicine, the development of the
      Wassermann Test and arsenical drugs, as well as war conditions, were important in
      putting syphilis on the public agenda in Belgium. However, the way in which new
      diagnostic and therapeutic techniques and devices were incorporated within post
      war VD policy depended on the reconciliation of a range of political,
      professional and moral agendas of interested health-political parties. Finally, a
      successful post-war VD policy depicted in terms of <<The Belgian Experience>> is
      discussed.

PMID- 15584176
TI  - [Correction of pectus excavatum by reverse "V"-shape cutting in the sternum:
      report of 2 cases].

PMID- 15584177
TI  - Does WIC work? The effects of WIC on pregnancy and birth outcomes.
AB  - Support for WIC, the Special Supplemental Nutrition Program for Women, Infants,
      and Children, is based on the belief that "WIC works." This consensus has lately
      been questioned by researchers who point out that most WIC research fails to
      properly control for selection into the program. This paper evaluates the
      selection problem using rich data from the national Pregnancy Risk Assessment
      Monitoring System. We show that relative to Medicaid mothers, all of whom are
      eligible for WIC, WIC participants are negatively selected on a wide array of
      observable dimensions, and yet WIC participation is associated with improved
      birth outcomes, even after controlling for observables and for a full set of
      state-year interactions intended to capture unobservables that vary at the state
      year level. The positive impacts of WIC are larger among subsets of even more
      disadvantaged women, such as those who received public assistance last year,
      single high school dropouts, and teen mothers.

PMID- 15584178
TI  - [Percutaneous coronary interventions for acute myocardial infarction using
      PercuSurge GuardWire distal balloon protection system: report of one case].

PMID- 15584179
TI  - [A case of neurofibromatosis type I with malignant growth and calvarial bone
      defect].

PMID- 15584180
TI  - [Angioimmunoblastic T-cell lymphoma with distinct follicular hyperplasia: report
      of one case].

PMID- 15584181
TI  - Ethical issues of egg donation.

PMID- 15584182
TI  - Genetic enhancement.

PMID- 15584183
TI  - The human chimera patent initiative.

PMID- 15584184
TI  - Equity in liver allocation.

PMID- 15584185
TI  - End of life decision-making for patients with dementia.

PMID- 15584186
TI  - Family demand for futile treatment.

PMID- 15584187
TI  - Informed consent for stem cell research using frozen embryos.

PMID- 15584188
TI  - Reason and repugnance.

PMID- 15584189
TI  - Should a medical practice accept a gift with strings attached?

PMID- 15584190
TI  - Inappropriate message for Australian nurses.

PMID- 15584191
TI  - Alginates and side-effects.

PMID- 15584192
TI  - Ageless bodies, happy souls: biotechnology and the pursuit of perfection.

PMID- 15584193
TI  - Liberty, privacy, and DNA databases.

PMID- 15584194
TI  - The paradox of conservative bioethics.

PMID- 15584195
TI  - Bioethics and the character of human life.

PMID- 15584196
TI  - Of embryos and empire.

PMID- 15584197
TI  - Why conservatives care about biotechnology.

PMID- 15584198
TI  - Eugenics--sacred and profane.

PMID- 15584199
TI  - From foe to friend: geographical and environmental factors and the control and
      eradication of smallpox in India.
AB  - Due to the highly visible nature of the disease, smallpox received a lot of
      attention from the colonial and independent Indian governments. An assessment of
      the changing official views about the impact of geographical and environmental
      factors on modes of variola causation and control presents insights into themes
      that are generally ignored in the existing historiography. Rather than being
      synchronised efforts, imposed top-down, provincial level officials in charge of
      running vaccination programmes were able to retain a great degree of autonomy and
      shape the nature of local immunisation drive. As a result, vaccination work in
      the country was often disjointed, marked by official disagreements about the
      usefulness of certain strategies and technological inputs, with these trends
      being most noticeable in rural areas. Thus, this study seeks to highlight the
      importance of recognising--and studying--the fractured nature of medical and
      public health administration in the South Asian sub-continent.

PMID- 15584200
TI  - Nationalism, Carrion's disease and medical geography in the Peruvian Andes.
AB  - During the turn of the 20th century medical geography in Peru concentrated in the
      study of a native disease (bartonellosis, also known as Carrion's disease and
      Verruga Peruana) and reinforced the relationship between the country's 'natural'
      regions (coast, highlands and Amazon) and different patterns of disease. Expert
      knowledge on these themes was portrayed as important not only for the practice of
      medicine but also for the development of the country. This knowledge was
      instrumental for an emergent local medical tradition and for legitimizing the
      authority, power and prestige of Lima's medical elite. The city was the capital
      of a country whose population was mainly Indian and rural, and lived in the
      highlands. This article studies the development of medical geography in Peru
      emphasizing the role played by Ernesto Odriozola, an influential clinician from
      Lima trained in Paris.

PMID- 15584201
TI  - ['Intervening is representing': medical campaigns that helped identify the
      prevalence of hookworm].
AB  - This paper compares anti-hookworm campaigns conducted in the early twentieth
      century in France, Germany, Brazil and West India. The populations that suffer
      from hookworm are not identical in the North and in the South. In tropical and
      semi-tropical regions hookworm is mainly found among poor peasants and is related
      to lack of hygiene, while in temperate climates hookworm was a professional
      disease of miners, a highly organized professional segment. Nevertheless, major
      disparities in the pattern of hookworm control did not reflect the North-South
      divide, but a difference between campaigns. These aimed at the eradication of
      hookworm infection (Germany and West-India) and at alleviating the effects of
      this infection on populations (France and Brazil). Maps that represented the
      prevalence of hookworm mirrored the aims of the sanitary campaign in which they
      were used: eradication of parasitic worms versus the reduction of the handicap
      induced by these worms. In public health as well, representing is intervening.
      And vice versa: patterns of intervention shape representations.

PMID- 15584202
TI  - Views from the periphery: discourses of race and place in French military
      medicine.
AB  - Numerous authors have interpreted the history of anthropological and medical
      conceptions of race in nineteenth century France as following a path mapped out
      by phrenology, anthropometry, and Paul Broca's version of physical anthropology.
      On balance, this has resulted in an historical narrative centered on Parisian
      intellectual life and one leaving the impression that by the 1890s
      anthropological theories had moved away from ethnological and cultural
      explanations toward more biological views of race. This article, by contrast,
      examines the world beyond Paris and the literatures of naval and army medicine
      from about 1830 to 1920. It describes the contours of a medical and
      anthropological pluralism in matters of race and ethnicity and argues that
      cultural and ethnological perspectives remained important to theorists of race
      through World War I.

PMID- 15584203
TI  - From miasma to asthma: the changing fortunes of medical geography in America.
AB  - Historians of modern medicine often divide their subject into two parts,
      separated by the bacteriological revolution of the late nineteenth century, when
      medicine supposedly became 'scientific' for the first time. The history of
      medical geography--to say nothing of other subjects--calls this common view into
      question. At least in the United States, students of medical geography, arguably
      the pre-eminent medical science in an age dominated by miasmatic theories of
      disease, readily adapted to the discovery of germs. And although bacteriology
      quickly eclipsed medical geography in the world of medicine, place remained an
      important consideration in treating asthma (and allergies generally) throughout
      the post-bacteriological period.

PMID- 15584204
TI  - Sulfa, penicillin, erythromycin, and cytochrome P-450.

PMID- 15584205
TI  - News for Kentucky physicians. Testimony presented by expert witnesses.

PMID- 15584206
TI  - Venous disorders.

PMID- 15584207
TI  - Sorry, we're all out.

PMID- 15584208
TI  - Mammography and breast cancer.

PMID- 15584209
TI  - Argon plasma coagulation (APC) in brain tumor surgery: experimental study and
      clinical experiences.
AB  - OBJECTIVE: The present study aims to provide preliminary results of the thermal
      effects on rat brain tissue after argon plasma coagulation (APC). It also
      presents and discusses the clinical experiences in the treatment of brain tumor
      using APC. MATERIALS AND METHODS: A controlled study of APC in the rat brain was
      conducted. Twelve rats were randomly divided into 2 experimental groups. In the
      first group (n = 6), histopathological evaluation was performed 2 days following
      the coagulation. In the second group (n = 6), the evaluation was performed 12
      days post operation. In a prospective study of APC-treated tumor tissue in 3
      patients, the depth of plasma penetration and histological alteration were
      evaluated. RESULTS: In the animal experiment, extent of tissue defect became
      significantly smaller after 12 days (p = 0.010). The maximum depth of tissue
      alteration after APC application was limited to 2.15 mm (range: 1.5-2.15 mm) at
      day 2. The histological alteration of tissue after the thermal injury can be
      divided into 3 zones. In addition, the depth of tissue alteration in the APC
      treated human brain tumor was measured in vertical and horizontal planes under
      light microscope. Similar to the animal experiment result, penetration of the
      plasma energy in human brain tumors was limited to a maximum of 2.13 mm (range:
      1.6-2.13 mm). CONCLUSION: The limited depth of energy penetration may confirm APC
      as a safe and beneficial tool for coagulation of human brain tissue. However,
      further clinical studies are required to evaluate the suitability and indications
      of this method in brain tumor treatment.

PMID- 15584210
TI  - MIB-1 labeling index in astrocytic tumors--a clinicopathologic study.
AB  - BACKGROUND: Although neuroimage and surgical techniques have improved
      substantially, the prognosis of patients with astrocytic tumors remains
      unchanged. The purpose of this study was to evaluate the proliferative activity
      in astrocytic tumors in different grades of malignancy and correlate it to other
      clinical features. PATIENTS AND METHODS: From archival paraffin-embedded surgical
      specimens of 40 patients of the Ribeirao Preto Medical School with World Health
      Organization grade II (n = 10), grade III (n = 5) and grade IV astrocytomas (n =
      25), the MIB-1 labeling index (LI) was determined using at least a half of the
      blocks per case. The results were correlated to the biological behavior of the
      tumors. The aims of this study were to determine the level of MIB-1 LI values
      (cut-off) that reflect differences in biological behavior of these tumors, the
      impact on survival of clinical features such as age, tumor location or extension
      of surgical removal as well as the adjuvant therapy. RESULTS AND CONCLUSIONS: As
      expected, a wide range of MIB-1 LI values was disclosed (mean of 2.35% in grade
      II astrocytomas to 12.28% in glioblastomas). A close relationship was found
      between MIB-1 LI and survival of patients with astrocytomas according to the
      histological grade. All but 1 recurrent tumor presented higher MIB-1 LI in the
      second biopsy, and the mean MIB-1 LI of the patients who died in the immediate
      postoperative period (n = 7) was higher in comparison to the MIB-1 LI of the
      respective grade. Postoperative radiation therapy was an important factor that
      affected the survival of patients with high-grade astrocytomas (p = 0.006). MIB-1
      LI cut-off of 3% divided the astrocytomas in 2 groups with significantly
      different survival (p < 0.001): median survival time of 12 months (low-grade)
      versus 45 months (high-grade). On the other hand, univariate analysis did not
      show any correlation between survival and extension of surgical resection
      (radical versus partial), tumor's location or patient's age at surgery.

PMID- 15584211
TI  - Rabies encephalitis following fox bite--histological and immunohistochemical
      evaluation of lesions caused by virus.
AB  - Rabies caused by fox bite is uncommon, most cases being caused by bite of rabid
      dogs (95%). We report a 45-year-old lady with rabies encephalomyelitis caused by
      bite of a rabid wild fox (Vulpes vulpes), a species prevalent in the Deccan
      plateaus of Central India. Though foxes are known to be susceptible to rabies,
      literature on the pathological changes caused by fox bite rabies in humans is
      scarce. Unlike the mild histological alterations described in canine rabies, a
      florid encephalitic process evolved in fox bite rabies, in our case, with intense
      microglial reaction, neuronophagia and perivascular inflammatory infiltrates
      despite clinical manifestation as a paralytic rabies. Immunostaining using
      polyclonal antibodies to the rabies viral nucleocapsid antigen and to the whole
      virion demonstrated high viral load within neurons with extensive spread along
      dendritic arborization and axonal tracts. Genomic sequence analysis demonstrated
      close homology with canine virus strain with only minor variations.

PMID- 15584212
TI  - Chordomas: a histological and immunohistochemical study of cases with and without
      recurrent tumors.
AB  - Chordomas are rare, slow-growing and often recurrent neoplasms being composed of
      various cell types (physaliferous, epitheloid, chondroid), thus, showing a wide
      range of histological features. To study the relationship between histological
      and immunohistochemical pattern and biological behavior according to different
      cell types, the authors studied 33 specimens of 17 patients with and without
      recurrent tumors. Additionally, the histological features according to nuclear
      atypia and mitotic activity of both groups were analyzed and compared with each
      other. Predominance of one cell type was observed in 19 specimens (10 were
      composed mainly of physaliferous, 8 of the epitheloid and one of chondroid cell
      type). In 7 cases, areas of chondroid differentiation were present. MIB
      proliferation index tended not to be higher in recurrent tumors but in cases with
      nuclear atypia and nuclear pleomorphism seems to be predictive for recurrency.
      Immunohistochemically, nearly all cell types (physaliferous, epithelial-like and
      cells of chondroid differentiation) of both recurrent and non recurrent chordomas
      stained positive for epithel membrane antigen (EMA), cytokeratins (KL1, AE1/AE3),
      S100, vimentin and negative for HMB45 and desmin. Positive staining for NSE was
      observed in 70% of cases, however, the chondroid componente stained negative in
      every case.

PMID- 15584213
TI  - Heavily lipidized, calcified giant cell glioblastoma in an 8-year-old patient,
      associated with neurofibromatosis type 1 (NF1): report of a case with long-term
      survival.
AB  - Giant cell glioblastoma (GCG-BM) with predominance of bizarre, multinucleated
      giant cells is a rare subtype of glioblastoma, however, its clinical behavior and
      histological features are still not fully understood. We report an unusual case
      of a heavily lipidized form of giant cell glioma corresponding mostly to GCGBM in
      a young patient with neurofibromatosis 1 (NF1). Histologically, the tumor
      revealed numerous characteristic histopathological features of giant cell
      glioblastoma including cellular pleomorphism with numerous giant tumor cells,
      pseudopalisades around necrotic foci and mitotic activity, accompanied by
      additional unique morphological elements such as massive lipidization of the
      neoplastic cells, abundant microcalcifications and angiomatous pattern of
      vascularization. Such aberrant morphology might be associated with the unusually
      long survival period of 12 years without clinical evidence of tumor recurrence.
      The coexistence of intracerebral heavily lipidized, calcified giant cell
      glioblastoma with NF1 has not been previously reported in literature.

PMID- 15584214
TI  - Meningioma with eosinophilic granular inclusions.
AB  - Rare meningiomas have been described that contain eosinophilic inclusions that
      have a granular or granulofilamentous ultrastructure. We describe a 66-year-old
      woman who developed a planum sphenoidale meningioma. Histologically, the tumor
      was composed of meningothelial cells arranged in fascicles and whorls, typical of
      a well-differentiated meningioma. Many tumor cells contained round
      intracytoplasmic eosinophilic inclusions that were periodic acid Schiff-negative
      and red on Masson trichrome. The inclusions were immunopositive for vimentin, and
      were immunonegative for epithelial membrane antigen, smooth muscle actin, desmin
      and type IV collagen. Ultrastructural examination showed the inclusions were
      composed of round to oval, well-demarcated, non-membrane-bound, osmiophilic
      granular material. The inclusions within this tumor had histochemical,
      immunohistochemical and ultrastructural properties not described in other
      reported meningiomas with eosinophilic granular or granulofilamentous inclusions.

PMID- 15584215
TI  - Malignant transformation of a spinal cord ganglioglioma--case report and review
      of the literature.
AB  - Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually have
      a benign clinical course. Rare cases display anaplastic features at the time of
      first presentation or progress to anaplastic gliomas over extended times. We
      report on a ganglioglioma of the spinal cord that recurred as a malignant glioma
      one and a half years after resection. The initial neoplasm was composed of a
      mixture of well-differentiated ganglionic and astrocytic cells. The recurrent
      tumor was an anaplastic small-cell glioma. The sole unusual aspect in the initial
      neoplasm was an abundance of small vessels with calcified walls, which mimicked a
      vascular malformation.

PMID- 15584216
TI  - Role of somatostatin and apoptosis in breathing control in sudden perinatal and
      infant unexplained death.
AB  - OBJECTIVES: To obtain basic information about the expression of somatostatin in
      the human central nervous system and, in particular, to evaluate its possible
      involvement in unexplained perinatal and in sudden infant death syndrome.
      MATERIAL: Sixty-seven brainstems from subjects aged from 30 gestational weeks to
      12 postnatal months, dying of both known and unknown causes, were selected for
      this study. The unexplained deaths included 17 sudden intrauterine deaths, 5
      sudden neonatal deaths and 28 sudden infant deaths. METHOD: All brainstems were
      fixed in 10% phosphate-buffered formalin, processed and embedded in paraffin,
      according to our protocol available on the web site: http://users.unimi.it/
      pathol/sids/riscontro_diagnostico_e.html. The distribution of the somatostatin in
      the brainstem was studied by immunohistochemistry on serial sections. RESULTS: We
      observed an intense somatostatin positivity in many brainstem nuclei prevalently
      involved in the respiratory activity (parabrachial/Kolliker-Fuse complex, locus
      coeruleus, hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii
      nucleus, ambiguus nucleus, reticular formation) in stillbirths. In 10 fetuses
      with unexplained death the neurons of the hypoglossus nucleus were somatostatin
      negative. In the postnatal deaths, we observed immunopositivity in the
      ventrolateral and ventral subnuclei of the tractus solitarii nucleus. Besides, in
      15 sudden infant death victims and in 1 control case, somatostatin-positive
      neurons were also present in the hypoglossus nucleus. In 10 of these 15 cases, a
      high apoptotic index was also reported. CONCLUSIONS: We suggest that
      abnormalities in the distribution of SS in the hypoglossus nucleus before and
      after birth may contribute to the induction of both fatal breathing in prenatal
      life and abnormal ventilatory control after birth leading to irreversible apnea.

PMID- 15584217
TI  - Free and bound phenolic compounds in barley (Hordeum vulgare L.) flours.
      evaluation of the extraction capability of different solvent mixtures and
      pressurized liquid methods by micellar electrokinetic chromatography and
      spectrophotometry.
AB  - Phenolic compounds exist in free and bound forms in cereals. The efficiency,
      reliability and suitability of recovering free phenolic compounds from barley by
      conventional, solid-liquid and pressurized solvent extractions, using different
      mixtures and methods, were tested. The extraction recovery of bound phenolics was
      evaluated using alkaline and acid hydrolyses. This study illustrates a rapid
      application of micellar electrokinetic chromatography for the analysis of free
      and bound phenolic compounds in barley samples. After developing a capillary
      electrophoresis optimization plan, barley phenols were analyzed within 5.5 min,
      using a buffer containing 20 mM sodium tetraborate, 10 mM sodium dodecyl sulfate
      and 5 mM KH2PO4 (pH 9), a 40cm x 50 microm capillary, 30kV and 30 degrees C. The
      selectivity of the extraction methods in recovering phenolic classes was
      evaluated by capillary electrophoresis and compared with spectrophotometric
      measurements. Electropherograms of free phenolic extracts showed flavan-3-ol
      compounds, proanthocyanidins and hydrolysable tannins. Aqueous acetone and
      aqueous ethanol solvents extracted the highest amount of catechins and
      hydrolysable tannins, respectively. The extraction yield of bound phenolic
      compounds (especially hydroxycinnamic acids) increased when the digestion time
      for alkaline hydrolysis was prolonged.

PMID- 15584218
TI  - Synthesis and application of molecularly imprinted polymer on selective solid
      phase extraction for the determination of monosulfuron residue in soil.
AB  - A novel sample clean-up procedure using molecularly imprinted polymer as the
      solid-phase extraction material for the determination of monosulfuron residue in
      soil samples has been developed. The molecularly imprinted polymer (MIP) was
      synthesized by non-covalent method with monosulfuron as the template. The
      selectivity and affinity of the MIP was evaluated by equilibrium adsorption and
      HPLC experiments, which demonstrated that the MIP has specific affinity for the
      template. The template-MIP interaction was studied by investigating the influence
      of different mobile phases on the retention of the template, which provided basic
      knowledge for the selection of the washing and elution solutions in the
      molecularly imprinted solid-phase extraction (MISPE) process. The study indicated
      that polar organic solvents with hydrogen bonding abilities have stronger eluting
      strength for the monosulfuron. After the MISPE procedure, a clean baseline was
      obtained in the HPLC quantification analysis. The recoveries of the method using
      the combination of MISPE and HPLC were above 93% and the R.S.D. was less than
      3.2% in the soil sample determinations. Low detection limit (0.08 microg g(-1),
      when defined as 3 times of the noise) was also obtained in the method evaluation
      study.

PMID- 15584219
TI  - New background correction method for liquid chromatography with diode array
      detection, infrared spectroscopic detection and Raman spectroscopic detection.
AB  - A new method to eliminate the background spectrum (EBS) during analyte elution in
      column liquid chromatography (LC) coupled to spectroscopic techniques is
      proposed. This method takes into account the shape and also intensity differences
      of the background eluent spectrum. This allows the EBS method to make a better
      estimation of the background eluent spectrum during analyte elution. This is an
      advantage for quantification as well as for identification of analytes. The EBS
      method uses a two-step procedure. First, the baseline spectra are modeled using a
      limited number of principal components (PCs). Subsequently, an asymmetric least
      squares (asLS) regression method is applied using these principal components to
      correct the measured spectra during elution for the background contribution. The
      asymmetric least squares regression needs one parameter, the asymmetry factor p.
      This asymmetry factor determines relative weight of positive and negative
      residuals. Simulations are performed to test the EBS method in well-defined
      situations. The effect of spectral noise on the performance and the sensitivity
      of the EBS method for the value of the asymmetry factorp is tested. Two
      applications of the EBS method are discussed. In the first application, the goal
      is to extract the analyte spectrum from an LC-Raman analysis. In this case, the
      EBS method facilitates easy identification of unknown analytes using spectral
      libraries. In a second application, the EBS method is used for baseline
      correction in LC-diode array detection (DAD) analysis of polymeric standards
      during a gradient elution separation. It is shown that the EBS method yields a
      good baseline correction, without the need to perform a blank chromatographic
      run.

PMID- 15584220
TI  - Estimation of significant solvent concentration ranges and its application to the
      enhancement of the accuracy of gradient predictions.
AB  - The solvent concentration range actually useful for gradient predictions is
      significantly narrower than the total range scanned in a gradient run. This
      range, called "solvent informative range" (SIR), if known with the highest
      accuracy, allows to predict gradient retention times (t(g) with minimal error.
      The small size of the SIR supports the application of the linear solvent strength
      theory (LSST). Furthermore, LSST allows a closed-form solution to the integral
      required to predict gradient retention times, which eliminates numerical
      integration, needed with other retention models. A methodology that calculates
      the SIR by applying error analysis, and uses it to improve the accuracy in the
      prediction of t(g) from isocratic experiments, is proposed. The importance of
      those mobile-phase compositions that do not contribute significantly to the
      prediction of t(g) is selectively attenuated within the prediction algorithm,
      relying the predictions more heavily on the SIR. As a result, t(g) was found to
      be predicted with similar accuracy using isocratic training data with regard to
      predictions based on gradient training data. The approach is useful for all
      situations where the chromatographer is able to provide predictions of retention
      at constant solvent concentration, and wish to predict the retention in gradient
      mode.

PMID- 15584221
TI  - Macroporous chitosan layer coated on non-porous silica gel as a support for metal
      chelate affinity chromatographic adsorbent.
AB  - A new immobilized metal affinity chromatography (IMAC) matrix was prepared by
      coordinating Cu2+ with cross-linked chitosan coated on non-porous silica gel (Cu
      CTS-SiO2). Macroporous structure could be formed on the coated layer by
      imprinting polyethylene glycol (PEG) in chitosan film. The surface morphology
      changes on Cu-CTS-SiO2 bead prepared in different condition were confirmed by
      scanning electron microscopy (SEM). Effects of chitosan and PEG content in
      coating solution, the molecular mass of PEG on the surface macropore formation
      and adsorption capacity of bovine serum albumin (BSA) were investigated. Results
      indicated that coating solution with 2% chitosan and 10% PEG 20000 was optimal.
      Batch experiments were also conducted for elucidating the optimal pH, the
      adsorption isotherm and adsorption kinetics of BSA. Adsorption isotherm of
      trypsin on the same adsorbent was also performed. Results showed that the support
      itself had low non-specific interaction with both BSA and trypsin. The maximum
      adsorption capacity for BSA and trypsin on the prepared IMAC adsorbent could
      reach 192 mg and 5000 IU, respectively calculated by every gram of chitosan. The
      binding and eluting condition for BSA were tested on column filled with the
      adsorbent. Crude BSA sample could be purified on the IMAC column.

PMID- 15584222
TI  - A fast, convenient and rugged procedure for characterizing the selectivity of
      alkyl-silica columns.
AB  - Previous work has shown that the selectivity of reversed-phase columns for HPLC
      can be described by means of five column parameters: H (hydrophobicity), S*
      (steric resistance), A (hydrogen-bond acidity), B (hydrogen-bond basicity) and C
      (cation-exchange capacity). Values of H, S*, etc. can be determined by carrying
      out retention measurements for 18 test solutes under standardized conditions. The
      reproducibility of the latter procedure has been evaluated by comparison testing
      in four different laboratories and found acceptable. An alternative 10-solute
      test procedure which is more reproducible and convenient (but somewhat less
      accurate), requires only 2-3 h per column.

PMID- 15584223
TI  - Choosing an equivalent replacement column for a reversed-phase liquid
      chromatographic assay procedure.
AB  - The column selectivity parameters (H, S*, A, B and C) described in the preceding
      paper [L.R. Snyder, A. Maule, A. Heebsch, R. Cuellar, S. Paulson, J. Carrano, L.
      Wrisley C.C. Chan, N. Pearson, J.W. Dolan, J.J. Gilroy, J. Chromatogr. A 1057
      (2004) 49-57] can be used to compare columns in terms of selectivity. A detailed
      procedure for such column comparisons is presented here, and evaluated by its use
      in finding suitable replacement columns for 12 different routine separations
      performed in five different pharmaceutical analysis laboratories.

PMID- 15584224
TI  - Origin of enhanced chiral selectivity by acidic additives for a polysaccharide
      based stationary phase.
AB  - The effects of ethanesulfonic acid (ESA) and n-butylamine as additives were
      studied for a wide variety of chiral compounds using the polysaccharide chiral
      stationary phase (CSP), Chiralpak AD. The mobile phase consisted of hexane
      ethanol (90:10, v/v). The additives typically had small effects, with one
      exception: the acidic additive had an enormous effect on the chiral selectivity
      of amino acid esters. The improved chiral selectivity was largely due to the
      longer retention of the later eluting enantiomer. Retention behavior of amines
      indicated that the higher selectivity for amino acid esters owes to increased
      hydrogen-bonding donation by the amine group of the analyte. Computation
      establishes the feasibility of a planar complex between the analyte and the
      cliral stationary phase, involving a pair of complementary hydrogen-bonding
      groups on each species, enabled by protonation of the analyte. Retention
      behaviors for a range of structures point to steric hindrance as the third
      interaction to comprise the requisite three interactions in chiral recognition.

PMID- 15584225
TI  - Highly sensitive and selective determination of 9, 10-phenanthrenequinone in
      airborne particulates using high-performance liquid chromatography with pre
      column derivatization and fluorescence detection.
AB  - 9,10-Phenanthrenequinone (PQ), is one of the components of diesel exhaust
      particulates, has potent harmful effects on human health. For the determination
      of PQ in airborne particulates, a highly sensitive and selective high-performance
      liquid chromatography (HPLC) method was developed with fluorescence detection
      following the pre-column fluorescent derivatization. PQ was derivatized with
      benzaldehyde as a derivatizing reagent in the presence of ammonium acetate to
      give fluorescent 2-phenyl-1H-phenanthro [9,10-d] imidazole. The maximum
      fluorescence intensity of the derivative was observed by the reaction with 0.2M
      benzaldehyde and 0.5 M ammonium acetate at 100 degrees C for 30 min. The HPLC
      separation of fluorescent derivative of PQ was performed within 20 min on an ODS
      column with a mixture of acetonitrile-water (55:45, v/v) as a mobile phase.
      Highly sensitive and selective determination of PQ was attained with the
      detection limit of 5 fmol (S/N = 3). By the proposed method, PQ in airborne
      particulates was successfully determined in the range 0.26-0.30 ng/m3 (n = 3).

PMID- 15584226
TI  - Preparative isolation and purification of coumarins from Peucedanum praeruptorum
      Dunn by high-speed counter-current chromatography.
AB  - A preparative high-speed counter-current chromatography (HSCCC) method for
      isolation and purification of coumarins from Peucedanum praeruptorum Dunn
      (Baihuaqianhu in Chinese) was successfully established by using light petroleum
      ethyl acetate-methanol-water as the two-phase solvent system in gradient elution
      mode. The upper phase of light petroleum-ethyl acetate-methanol-water (5:5:5:5,
      v/v) was used as the stationary phase of HSCCC. The mobile phase used in HSCCC
      was the lower phase of light petroleum-ethyl acetate-methanol-water (5:5:5:5,
      v/v) and light petroleum-ethyl acetate-methanol-water (5:5:6.5:3.5, v/v) that was
      changed in gradient. Four kinds of coumarins and another unknown compound were
      obtained and yielded 5.3 mg of qianhucoumarin D, 7.7 mg of Pd-Ib, 35.8 mg of (+)
      praeruptorin A, 31.9 mg of (+)-praeruptorin B and 6.4 mg of unknown compound with
      the purity of 98.6%, 92.8%, 99.5%, 99.4% and 99.8% in one-step separation,
      respectively. The structures of the coumarins were identified by 1H NMR and 13C
      NMR.

PMID- 15584227
TI  - Purification of the isoflavonoid puerarin by adsorption chromatography on cross
      linked 12% agarose.
AB  - The isoflavonoid puerarin in extracts of the well-known traditional Chinese drug
      Radix puerariae (root of the plant Pueraria lobata) can be separated from other
      isoflavonoids by adsorption chromatography on the cross-linked 12% agarose gel
      Superose 12 equilibrated in distilled water. The adsorption is totally quenched
      by the addition of 50% acetic acid. The separation of the isoflavonoids is
      tentatively ascribed to interaction with the residues of the cross-linking
      reagents used in the manufacturing process of Superose 12. Thus, no useful
      separation can be achieved with non-cross-linked 12% agarose gel media. Symmetric
      elution profiles at high sample loadings (16 mg on a 24 ml column) suggest linear
      adsorption isotherms for the isoflavonoids.

PMID- 15584228
TI  - Protein separation with surfactant-coated octadecylsilyl silica involving
      Cibacron blue 3GA-conjugated nonionic surfactant.
AB  - A novel medium for protein separation, namely affinity admicelle, was prepared by
      mixing of octadecylsilyl (ODS) silica gels, a polyoxyethylene-type nonionic
      surfactant (Triton X-100), and a surfactant-conjugated substrate (affinity
      ligand) in an aqueous solution. The ligand was synthesized by mixing a triazine
      dye (Cibacron Blue 3GA, CB) and a polyethylene glycol monooleyl ether (C18EO7,
      C18EO10, or C18EO20) having different length of polyoxyethylene moiety in weakly
      alkaline solutions. The amount of Triton X-100 sorbed on 1 g of ODS silica was
      0.2 mmol. Affinity ligands having highly hydrophobic oleyl group were
      predominantly sorbed on ODS silica. The losses of Triton X-100 and affinity
      ligand were within 0.3% and negligible by washing the admicelles were with a 25
      fold volume of 1 mM Tris-HCl solution (pH 7.4). The coating ODS silica with
      Triton X-100 was effective to prevent the irreversible sorption of albumin
      (bovine, serum). An NADH-dependent enzyme, alcohol dehydrogenase (ADH, yeast),
      was successfully collected on the admicelles involving CB-conjugated ligands (CB
      C18EO20). The maximum collection of ADH to 90 mg/ml of affinity admicelles was
      68+/-4%. However, CB-C18EO7 and CB-C18EO10 having shorter polyoxyethylene unit
      were not available, suggesting the requirement of the spacer moiety in the
      affinity ligand. The recovery and purification factor based on the ratio of
      activity (unit)/protein (mg) from Whatman DE52-treated yeast extract was 27% and
      12, respectively.

PMID- 15584229
TI  - Fully automated online multi-dimensional protein profiling system for complex
      mixtures.
AB  - For high throughput proteome analysis of highly complex protein mixtures, we have
      constructed a fully automated online system for multi-dimensional protein
      profiling, which utilizes a combination of two-dimensional liquid chromatography
      and tandem mass spectrometry (2D-LC-MS-MS), based on our well-established offline
      system described previously [K. Fujii, T. Nakano, T. Kawamura, F. Usui, Y. Bando,
      R. Wang, T. Nishimura, J. Proteome Res. 3 (2004) 712]. A two-valve switching
      system on a programmable auto sample injector is utilized for online two
      dimensional chromatography with strong cation-exchange (SCX) and reversed-phase
      (RP) separations. The SCX separation is carried out during the equilibration of
      RP chromatography and the entire sequence of analysis was performed under fully
      automated conditions within 4 h, based on six SCX fractionations, and 40 min
      running time for the two-dimensional RP chromatography. In order to evaluate its
      performance in the detection and identification of proteins, digests of six
      standard proteins and yeast 20S proteasome have been analyzed and their results
      were compared to those obtained by the one-dimensional reversed-phase
      chromatography system (ID-LC-MS-MS). The 2D-LC-MS-MS system demonstrated that
      both the number of peptide fragments detected and the protein coverage had more
      than doubled. Furthermore, this multi-dimensional protein profiling system was
      also applied to the human 26S proteasome, which is one of the highly complex
      protein mixtures. Consequently, 723 peptide fragments were identified as 31
      proteasome components, together with other coexisting proteins in the sample. The
      identification could be comprehensively performed with a 63% sequence coverage on
      an average, and additionally, with modifications at the N-terminus. These results
      indicated that the online 2D-LC-MS-MS system being described here is capable of
      analyzing highly complex protein mixtures in a high throughput manner, and that
      it would be applicable to dynamic proteomics.

PMID- 15584230
TI  - Integrated process for purification of plasmid DNA using aqueous two-phase
      systems combined with membrane filtration and lid bead chromatography.
AB  - An integrated process for purifying a 6.1 kilo base pair (kbp) plasmid from a
      clarified Escherichia coli cell lysate based on an ultra/diafiltration step
      combined with polymer/polymer aqueous two-phase system and a new type of
      chromatography is described. The process starts with a volume reduction
      (ultrafiltration) and buffer exchange (diafiltration) of the clarified lysate
      using a hollow fibre membrane system. The concentrated and desalted plasmid
      solution is then extracted in a thermoseparating aqueous two-phase system, where
      the contaminants (RNA and proteins) to a large extent are removed. While the
      buffer exchange (diafiltration) is necessary in order to extract the plasmid DNA
      exclusively to the top phase, experiments showed that the ultrafiltration step
      increased the productivity of the aqueous two-phase system by a factor of more
      than 10. The thermoseparated water phase was then subjected to a polishing step
      using lid bead chromatography. Lid beads are a new type of restricted access
      chromatography beads, here with a positively charged inner core that adsorbed the
      remaining RNA while its inert surface layer prevented adsorption of the plasmid
      DNA thus passing in the flow-through of the column. Differently-sized plasmid DNA
      in the range of 2.7-20.5 kbp were also partitioned in the aqueous two-phase
      system. Within this size range, all plasmid DNA was exclusively extracted to the
      top phase. The complete process is free of additives and easy scalable for use in
      large scale production of plasmid DNA. The overall process yield for plasmid DNA
      was 69%.

PMID- 15584231
TI  - Enhancement of evaporative light scattering detection in high-performance liquid
      chromatographic determination of neomycin based on highly volatile mobile phase,
      high-molecular-mass ion-pairing reagents and controlled peak shape.
AB  - In the frame of the development of a novel HPLC-ELSD (evaporative light
      scattering detection) method for the determination of the aminoglycoside
      antibiotic neomycin sulfate, the influence of mobile phase composition and peak
      broadening on ELSD response was evaluated. ELSD response was enhanced by: (a)
      increase of mobile phase volatility (solvents examined: water, acetonitrile,
      methanol and acetone), (b) increase of molecular mass of ion-pairing species
      [acidic reagents tested: formic, acetic, trifluoroacetic, trichloroacetic and
      heptafluorobutyric acid (HFBA)], and (c) decrease of peak width and asymmetry
      obtained by controlling the concentration of the ion-pairing acidic reagent
      (HFBA). Utilizing a Waters ODS-2 C18 Spherisorb column, evaporation temperature
      of 45 degrees C and nitrogen pressure of 3.5 bar, the optimized mobile phase was
      water-acetone (50:50), containing 11.6 mM HFBA, in an isocratic mode at a rate of
      1.0 ml/min. Neomycin was eluted at 4.9 min, with asymmetry factor 1.3.
      Logarithmic calibration curve was obtained from 2 to 50 microg/ml (r > 0.9997).
      Limit of detection (LOD) was 0.6 microg/ml and R.S.D. = 1.7% (n = 3, 3.3
      microg/ml). In raw materials, the simultaneous determination of sulfate (LOD = 3
      microg/ml, R.S.D. = 1.7%, r> 0.9998) and of minor impurities was feasible. The
      developed method was also applied for the determination of neomycin in
      pharmaceutical formulations (powder, aerosol and cream) without any interference
      from excipients (recovery from spiked samples ranged from 99 to 102%) and a
      %R.S.D. of <2.1 (n = 3). The HPLC-ELSD method was also found applicable in the
      determination of neomycin in animal feeds (LOQ=0.2%) without any interference
      from the feed matrices.

PMID- 15584232
TI  - Fingerprinting of Salvia miltiorrhiza Bunge by non-aqueous capillary
      electrophoresis compared with high-speed counter-current chromatography.
AB  - The component of the traditional Chinese medicine (TCM) can be influenced by
      soil, climate, and growth stage, and fingerprint is an important means in its
      quality control. Our previous studies showed that high-speed counter-current
      chromatography (HSCCC) was helpful in the development of fingerprint of TCM.
      Since the HSCCC method is new, it is necessary to compare it with conventional
      ones, such as high-performance liquid chromatography (HPLC), thin-layer
      chromatography (TLC) and high-performance capillary electrophoresis (HPCE).
      Comparison with HPLC was conducted in our previous study. In this study, HSCCC
      was compared with non-aqueous capillary electrophoresis (NACE). With NACE, seven
      stable components were separated within 55 min, respectively, from three crude
      samples of Salvia miltiorrhiza Bunge from different growth locations. In HSCCC
      separation, 12 components were separated, respectively, with good correspondence
      and precision within 13 h. Both NACE and HSCCC were effective in showing whole
      concentration distribution of all kinds of constituents. Principles of these two
      methods were very different, which led to different elution sequences and
      relative contents of peaks. HSCCC showed better performance in analysis of
      tanshinones, which made its fingerprint containing more chemical information than
      that of NACE. It was further proven that HSCCC could be a feasible and cost
      effective method in the development of the fingerprint of TCM.

PMID- 15584233
TI  - High-performance liquid chromatographic method with quantitative comparisons of
      whole chromatograms of raw and steamed Panax notoginseng.
AB  - A high-performance liquid chromatographic (HPLC) method coupled with
      chromatographic pattern matching was developed to differentiate whole
      chromatograms of raw and steamed Panax notoginseng objectively and
      quantitatively. The major peaks differentiating chromatograms of raw and steamed
      samples were also identified for the first time in this herb. The raw and steamed
      P. notoginseng roots and its products were successfully differentiated. The
      quantitative differences between the chromatograms were correlated to the
      duration of steaming. Chromatographic pattern matching allows rapid, simple,
      automated, and quantitative comparisons of complex chromatograms. It is a useful
      tool in ensuring safety and quality of herbal products.

PMID- 15584234
TI  - Comparison of series 5 gas chromatography column performances from a variety of
      manufacturers for separation of chlorinated dibenzo-p-dioxins and dibenzofurans
      using high-resolution mass spectrometry.
AB  - An extended study of seven fused silica capillary gas chromatographic (GC)
      columns has been conducted with regard to separation of international toxic
      equivalent factor (I-TEF) isomers (tetra- through octa-chlorinated at 2,3,7,8
      positions) of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans
      (PCDDs/PCDFs) from closely co-eluted other isomers using high-resolution gas
      chromatography-high-resolution mass spectrometry (HRGC-HRMS). The data are
      explicated in mass chromatograms of Series 5 GC columns from a variety of
      manufacturers (Varian CP-Sil 8 CB LowBleed/MS, Phenomenex ZB-5UMS, Agilent HP
      5MS, Restek Rtx-5MS, Supelco Equity-5, J&W Scientific DB-5 and DB-5MS), according
      to relative retention times, and 2,3,7,8-substituted isomer concentrations for
      each of the columns tested. Results showed differences between 5% phenyl methyl
      silicone and 5% silphenylene (Si-arylene) silicone polymer type GC stationary
      phases in separation of 2,3,7,8-substituted PCDDs/PCDFs from closely co-eluted
      isomers. The separation differences for Si-arylene type columns resulted in lower
      toxic equivalence (TEQ) values compared to the siloxane-based columns. Because of
      differences in product nomenclature and manufacturing practices by various
      manufacturers, incorrect assumptions and comparisons may be made regarding the
      interchangeability of these columns for PCCD/PCDF separations. The data presented
      are the most comprehensive to date and provide a valuable addition to operational
      criteria for the standard US Environmental Protection Agency methods 1613b and
      8290.

PMID- 15584235
TI  - Analysis of endocrine disrupting alkylphenols, chlorophenols and bisphenol-A
      using hollow fiber-protected liquid-phase microextraction coupled with injection
      port-derivatization gas chromatography-mass spectrometry.
AB  - Liquid-phase microextraction (LPME) coupled with gas chromatography-mass
      spectrometry were used to determine alkylphenols (APs), chlorophenols (CPs) and
      bisphenol-A (BPA) in aqueous samples. APs, CPs and BPA are highly polar compounds
      and need to be derivatized before analysis by GC-MS. In this work, they were
      derivatized in the GC injection port with bis(trimethylsilyl)trifluoroacetamide
      (BSTFA). The analytes were extracted directly from 5 ml of sample solution using
      5 microl of organic solvent though a porous polypropylene hollow fiber. The
      hollow fiber, filled with an immiscible organic solvent (ca. 5 microl), was
      immersed in the sample solution which was stirred during the 30-min extraction.
      An aliquot (2 microl) of the extract and 2 microl of BSTFA were then
      consecutively injected into the GC injection port. Extraction parameters such as
      extraction time, pH of sample, concentration of salt added, and stirring rate
      were optimised. The proposed LPME provided a good average enrichment factor of up
      to 162-fold, reproducibility ranging from 5.9 to 13.9% (n = 4), and good
      linearity (r2 = 0.995) for spiked water samples. The limits of detection (LODs)
      ranged between 0.005 and 0.015 microgl(-1) (S/N = 3) using GC-MS with selective
      ion monitoring and limits of quantification were in the range of 0.012-0.026
      microg l(-1). A comparative study was performed between LPME, headspace solid
      phase microextraction (HS-SPME) and liquid-liquid extraction (LLE). The results
      obtained suggested that hollow fiber LPME was a rapid, simple and efficient
      technique for APs, CPs and BPA, and provided a good alternative to SPME and LLE.
      Finally, the proposed method was applied to monitor Singapore coastal water
      samples.

PMID- 15584236
TI  - Capillary gas chromatographic separation of bile acid acyl glycosides without
      thermal decomposition and isomerization.
AB  - A direct method for the capillary gas chromatographic (cGC) separation of the
      acyl glycosides of bile acids was successfully attained. The free acyl glycosides
      were derivatized to their complete trifluoroacetyl (TFA) derivatives with N
      methyl-bis(trifluoroacetamide). The highly volatile TFA derivatives were
      chromatographed on a short-length (10 m), narrow-bore (0.1 mm) capillary column
      coated with a thin film (0.1 microm) of 5% phenyl polysilphenylene-siloxane at a
      column temperature below 280 degrees C. Each exhibited a single, well-separated
      peak of the theoretical shape without any accompanying peaks due to the thermal
      decomposition and isomerization. The bile acid 24alpha-glucosides were always
      eluted faster than the corresponding 24beta-glucosides, which eluted before the
      corresponding 24beta-galactosides. The method could be usefully applied to
      biosynthetic and metabolic studies of bile acid acyl glycosides in biological
      materials.

PMID- 15584237
TI  - Sensitive method for the determination of roxarsone using solid-phase
      microextraction with multi-detector gas chromatography.
AB  - We describe the development, optimization, and application of a novel method for
      the unequivocal identification and quantification of roxarsone (3-nitro-4
      hydroxyphenylarsonic acid, 3-NHPAA) at low microg L(-1) levels. The method is
      based on capillary gas-liquid chromatography with parallel quadrupole ion-trap
      mass spectrometric (QIT-MS) and pulsed flame photometric detection (PFPD). The
      sensitive method couples the arsenic specificity of PFPD with the high
      selectivity of molecular MS for the determination of roxarsone, dimethylarsenic
      acid (DMAA), and monomethylarsonic acid (MMAA) in complex matrices. Analytes were
      derivatized based on the approach we previously reported [B. Szostek, J.H.
      Aldstadt, J. Chromatogr. A 807 (1998) 253 and D.R. Killelea, J.H. Aldstadt, J.
      Chromatogr. A 918 (2001) 169] for the reaction of organoarsenicals with 1,3
      propanedithiol (PDT). The cyclic dithiaarsenolines formed were extracted from the
      sample matrix in the liquid phase by solid-phase microextraction (SPME). The
      optimized SPME conditions employed a 65 microm polydimethlysiloxane
      divinylbenzene (PDMS-DVB) fiber, extraction temperature of 70 degrees C and fiber
      equilibration time of 15.0 min. The mass spectrum of the dithiaarsenoline of
      roxarsone showed a base peak that corresponded to the predicted structure at m/z
      319 and the tell-tale peak of an arsenic compound derivatized with PDT at m/z
      181. Further peaks at m/z 149 and 228 were observed and found to be unique to
      roxarsone, formed by an interesting internal rearrangement of the ONOH
      functionality. A linear calibration model was prepared for roxarsone over an
      environmentally relevant range (0.0-100 microg L(-1)) and a detection limit of
      2.69 microg L(-1) (3sigma) was observed. The method was applied to several
      fortified environmental surface water samples (50 microg L(-1)) where the average
      recovery for roxarsone was 103+/-10.9%.

PMID- 15584238
TI  - Determination of 2,4,6-tribromoaniline in the color additives D&C Red Nos. 21 and
      22 (Eosin Y) using solid-phase microextraction and gas chromatography-mass
      spectrometry.
AB  - The present work demonstrates the presence of an impurity, 2,4,6-tribromoaniline
      (TBA), in the color additives D&C Red Nos. 21 and 21 lake (21L) and describes the
      determination of TBA in certified lots of D&C Red Nos. 21, 21L and 22 (Eosin Y).
      A method was developed using solid-phase microextraction with [13C6]TBA as an
      internal standard followed by gas chromatography-mass spectrometry analysis. Test
      portions from 23 lots of US-certified color additives D&C Red Nos. 21, 21L and 22
      were analyzed for TBA using the new method. These lots represent domestic (four)
      and foreign (four) manufacturers that requested certification for the color
      additives during the past 2 years. Of the test portions analyzed, 12 (52.2%)
      contained TBA in amounts ranging from 19.9 to 638.9 ppm with an average value of
      approximately 278.7 ppm. The remaining 11 (47.2%) test portions contained no
      detectable TBA or less than 0.01 ppm, which is the limit of quantification of the
      present method. The wide range of TBA levels found in lots submitted for
      certification suggest that the contamination with TBA may be avoided or
      significantly decreased through appropriate changes in the color-manufacturing
      process.

PMID- 15584239
TI  - Static headspace gas chromatographic method for quantitative determination of
      residual solvents in pharmaceutical drug substances according to european
      pharmacopoeia requirements.
AB  - A static headspace (HS) gas chromatographic method for quantitative determination
      of residual solvents in a drug substance has been developed according to European
      Pharmacopoeia general procedure. A water-dimethylformamide mixture is proposed as
      sample solvent to obtain good sensitivity and recovery. The standard addition
      technique with internal standard quantitation was used for ethanol,
      tetrahydrofuran and toluene determination. Validation was performed within the
      requirements of ICH validation guidelines Q2A and Q2B. Selectivity was tested for
      36 solvents, and system suitability requirements described in the European
      Pharmacopoeia were checked. Limits of detection and quantitation, precision,
      linearity, accuracy, intermediate precision and robustness were determined, and
      excellent results were obtained.

PMID- 15584240
TI  - Matrix media selection for the determination of residual solvents in
      pharmaceuticals by static headspace gas chromatography.
AB  - The influence of the matrix medium used for the determination of residual
      solvents in pharmaceuticals by static headspace gas chromatography was
      investigated. The purpose of this paper is to propose a guide for the choice of a
      matrix medium suitable for the determination of residual solvents of interest.
      Dimethylsulfoxide (DMSO), N,N-dimethyformamide (DMF), N,N-dimethylacetamide
      (DMA), benzyl alcohol (BA), 1,3-dimethyl-2-imidazolidinone (DMI) and water were
      studied as matrix media, and seventeen solvents used for the synthesis and
      purification of drug substances were used as target analytes. The peak shape of
      each analyte was not affected by the matrix medium, whereas the peak intensities
      for all solvents were strongly affected by the matrix medium; for example, the
      peak intensity of methanol in a BA matrix was more than four times that in a DMSO
      matrix. With a few exceptions, the peak intensities are approximately doubled for
      every 20 degrees C rise in equilibrium temperature between 80 and 140 degrees C,
      and there is no difference in this behavior among the matrix media. In addition,
      the formation of artifacts from the matrix media, upon heating in a headspace
      sampling apparatus, was investigated. Artifacts were also formed following
      ultrasonication of sample solutions used to increase dissolution of the sample
      into the matrix medium selected. These artifacts included benzene and toluene
      which were restricted as Class 1 and 2 toxic solvents in the ICH guideline.

PMID- 15584241
TI  - Application of a headspace mass spectrometry system to the differentiation and
      classification of wines according to their origin, variety and ageing.
AB  - The system based on coupling a headspace sampler to a mass spectrometer (HS-MS),
      considered a kind of electronic nose (e-nose), is an emerging technique in the
      field of food aroma analysis. The global mass spectrum this system provides is a
      fingerprint of each sample analysed that contains the information related to
      volatile composition of the sample. The use of chemometric techniques allows to
      compare the spectra of the samples and then, to classify them according to
      different properties. In this paper, we present the development of a method for
      wine analysis using a HS-MS system and multivariate analysis techniques. The
      method was successfully applied to differentiate and classify wines according to
      its origin, variety and ageing. The main advantages of the proposed methodology
      are the minimum sample preparation required and the speed of analysis (10
      min/sample).

PMID- 15584242
TI  - Quantitative determination of hydrogen in solids by gas chromatography.
AB  - Processes such as electroplating or acid cleaning are notorious causes of post
      processing failure through hydrogen embrittlement. So, the determination of
      amounts of hydrogen in metals is of great importance. An analysis method for
      investigation of H content in solids has been established based on hot extraction
      and gas chromatography system. Hot extraction in inert gas enables complete
      and/or partial removal of the hydrogen from the samples. A gas chromatography
      system is used to determine quantitatively the amount of thermally desorbed
      hydrogen. An investigation of the baking operating conditions is made of the
      hydrogen desorption rate of zinc-plated steel parts. Then, an analysis of the
      polarisation conditions upon chromium electroplating is given.

PMID- 15584243
TI  - Preparative isolation and purification of psoralen and isopsoralen from Psoralea
      corylifolia by high-speed counter-current chromatography.
AB  - Psoralen and isopsoralen were separated from Psoralea corylifolia by high-speed
      counter-current chromatography (HSCCC). A two-phase solvent system composed of n
      hexane-ethyl acetate-methanol-water (5:5:4.5:5.5, v/v) was used for HSCCC
      separation, and yielded, from 100 mg of crude extract, 39.6 mg of psoralen and
      50.8 mg of isopsoralen each at over 99% purity as determined by high performance
      liquid chromatography (HPLC). The identification of psoralen and isopsoralen were
      performed with 1H NMR and 13C NMR.

PMID- 15584244
TI  - Direct high-performance liquid chromatographic separation of unusual secondary
      amino acids and a comparison of the performances of Chirobiotic T and TAG
      columns.
AB  - Two macrocyclic glycopeptide antibiotic-type chiral stationary phases (CSPs)
      based on native teicoplanin and teicoplanin aglycone, Chirobiotic T and TAG,
      respectively, were evaluated with regard to the high-performance liquid
      chromatographic separation of the enantiomers of 10 secondary alpha-amino acids
      (imino acids). The chromatographic results are given as the retention, separation
      and resolution factors, together with the enantioselective free energy difference
      corresponding to the separation of the enantiomers. By application of these two
      CSPs, excellent resolutions were achieved for the investigated compounds by using
      reversed-phase mobile mode systems. The separation conditions were optimized by
      variation of the mobile phase composition. The difference in enantioselective
      free energy between the aglycone CSP and the teicoplanin CSP for these particular
      amino acids ranged between 0.70 and -1.83 kJ mol(-1). It was established that
      better enantioseparations of the secondary alpha-amino acids were attained in
      most cases on the aglycone CSP.

PMID- 15584245
TI  - Simple high-performance liquid chromatographic method for determination of
      atropine and obidoxime in a parenteral injection device.
AB  - Atropine and obidoxime in a parenteral injection device are determined by simple
      HPLC method simultaneously without any pretreatment at 228 nm. The relative
      standard deviations (R.S.D.) were below 1.6% for the compounds. The correlation
      coefficient was greater than 0.999 for both compounds in the calibration range.
      The recoveries at 5 mg/L concentration averaged as 95% for atropine and 102% for
      obidoxime. The uncertainty of the measurements for atropine and obidoxime was
      2.8% and 2.4%, respectively.

PMID- 15584246
TI  - Separation of rosemary antioxidant compounds by supercritical fluid
      chromatography on coated packed capillary columns.
AB  - Antioxidant compounds in rosemary extracts obtained by supercritical fluid
      extraction (SFE) were separated by supercritical fluid chromatography (SFC) on
      packed capillary columns. The columns contained silica particles coated with SE
      54 (5% phenyl, 95% methyl silicone) and Carbowax 20 M [poly(ethylene glycol)].
      The use of coated packed capillary columns allowed the separation of polar
      compounds by SFC with neat CO2. The SFC conditions were selected on the basis of
      previous work. High pressures (up to 370 atm; 1 atm = 10,325 Pa) and moderate
      temperatures (up to 100 degrees C) were used to separate the compounds
      responsible for the antioxidant activity such as carnosic acid and camosol while
      lower pressures were sufficient to separate the compounds of the essential oil.

PMID- 15584247
TI  - Improvement of heat dissipation for polydimethylsiloxane microchip
      electrophoresis.
AB  - Effective removing of Joule heat in polymer-based microchip system is an
      important factor for high efficient separation because of lower heat conductivity
      of polymers than silica or glass. In this paper, a new kind of
      polydimethylsiloxane (PDMS) microchip electrophoresis system integrated with a
      laser-induced fluorescence detector has been successfully constructed on the
      basis of a commercial heat sink for computer CPU (central processor unit).
      Experimental results on separation current using high concentration running
      buffers demonstrated that heat dissipation of PDMS/PDMS microchip system was
      significantly improved. Furthermore, with this integrated system, theoretical
      plate number of fluorescein using 100 mM phosphate-buffered saline + 1 mM sodium
      dodecyl sulfate as running buffer was determined to be 2750 (for 2.5-cm
      separation channel, corresponding to 110,000/m). This high separation efficiency
      demonstrated that such heat sink-based polymer microchip system could be
      effectively applied for high-concentration buffers.

PMID- 15584248
TI  - Interactions of Pb2+ with fulvic acid by electrophoretically mediated on
      capillary microanalysis.
AB  - Electrophoretically mediated microanalysis (EMMA) was used to monitor the on
      column complexation of Pb2+ and fulvic acid (FA). Electropherograms revealed
      several characteristic regions, the areas of which correlate with the metal
      concentration. The analysis of the electropherograms suggests that at least two
      different complexes are formed. Therefore, the EMMA is a prospective technique
      for structural investigation of humic substances (HS).

PMID- 15584249
TI  - Effect of physical exercise training on health-related quality of life and
      exercise tolerance in patients with left ventricular dysfunction.
AB  - OBJECTIVES: The improvement of exercise tolerance and quality of life (QOL) are
      essential in the treatment of patients with heart failure. The influence of
      physical exercise training on QOL was investigated in patients with left
      ventricular dysfunction. METHODS: Health-related QOL was evaluated using the
      Medical Outcomes Study Short-Form 36 Health Status Survey (SF-36) before and 3
      months after individualized exercise training determined by cardiopulmonary
      exercise testing in 65 patients. The 44 patients who could carry out more than
      two-thirds of the prescribed exercise were classified into two groups: Group A
      (11 patients)with left ventricular ejection fraction < 40% and Group B (33
      patients) with left ventricular ejection fraction > or = 40%. The remaining 21
      patients served as the control group. RESULTS: The mean value of SF-36 improved
      significantly with exercise training only in Group A (50.8 +/- 25.3 to 62.1 +/-
      22.2, p < 0.05). Group A also had an increase in peak Vo2 (18.9 +/- 3.5 to 21.4
      +/- 3.6 ml/min/kg, p < 0.005) and a decrease in brain natriuretic peptide. The 24
      patients (9 in Group A, 15 in Group B) with improved SF-36 values after the
      exercise training showed a negative correlation between the change of the mental
      component summary and the peak Vo2 (r = - 0.606, p < 0.05). CONCLUSIONS: Exercise
      training improves both the QOL, especially the mental component, and the exercise
      tolerance in patients with left ventricular dysfunction.

PMID- 15584250
TI  - [Efficacy of transesophageal echocardiography in patients with cardiac arrest or
      shock].
AB  - OBJECTIVES: Only a few examinations are available to critically ill patients. We
      assessed the efficacy of transesophageal echocardiography (TEE) in the management
      of patients with cardiac arrest or shock. METHODS: Among a total of 2,021
      patients who underwent TEE over the past 13 years at our institution, we reviewed
      18 patients who underwent TEE during cardiac arrest or shock. RESULTS: TEE was
      performed in four patients with cardiac arrest and in 14 patients with shock. In
      12 (67%) of 18 patients, TEE identified the following abnormalities: aortic
      dissection in four, ruptured thoracic aortic aneurysm in two, papillary muscle
      rupture in two, left ventricular free wall rupture in two, postoperative cardiac
      tamponade in one and ruptured chordae tendineae in one. TEE excluded suspected
      cardiac abnormality in two other patients. Transthoracic echocardiography could
      not be performed in 8 of 18 patients, and showed poor quality of images in the
      remaining 10 patients. Of the 12 patients with a diagnosis based on TEE, three
      patients died during cardiopulmonary resuscitation, whereas nine patients were
      treated with emergent surgery and six of these survived to hospital discharge.
      CONCLUSIONS: TEE is feasible even in patients with cardiac arrest or shock, and
      can play an important role in establishing the diagnosis and determining the
      treatment of such patients.

PMID- 15584251
TI  - [Usefulness of conscious sedation with midazoram during transesophageal
      echocardiographic examination].
AB  - OBJECTIVES: Although transesophageal echocardiography is useful to identify
      various cardiovascular diseases, the semi-invasive nature of the examination
      hampers its routine application. We investigated whether conscious sedation using
      a low dose of intravenous midazoram was safe and useful during the examination.
      METHODS: We asked 55 consecutive patients undergoing transesophageal
      echocardiography (44 with midazoram, mean age 59 +/- 16 years, and 11 without
      midazoram, mean age 62 +/- 8 years) and the examiners about the effects of
      midazoram using a questionnaire. RESULTS: The mean dose of midazoram was 2.2 mg
      (range 1-3.5 mg). All examinations were done without any adverse events. Eighty
      two percent of the patients with midazoram considered the examination under
      conscious sedation tolerable, whereas 91% without midazoram felt it untolerable.
      Most examiners felt manipulation of the echo probe was easier in patients with
      midazoram than in those without (69% vs 27%). CONCLUSIONS: Conscious sedation
      with a low dose of intravenous midazoram facilitated and increased patient
      tolerance during transesophageal echocardiographic examination.

PMID- 15584252
TI  - Complete proximal occlusion of all three main coronary arteries complicated with
      a left main coronary aneurysm: a case report.
AB  - A 68-year-old woman with recurrent chest pain was referred to our institution.
      Coronary angiography showed 100% obstruction of the left main trunk, the proximal
      right coronary artery with good collaterals to the left anterior descending
      artery and left circumflex artery along the conus artery. Emergency surgical
      revascularization was undertaken with two saphenous vein grafts. The saphenous
      vein grafts were placed in the left anterior descending artery, obtuse marginal
      branch and the posterolateral and posterior descending coronary arteries with
      excellent flow. The postoperative course was uneventful and follow-up angiography
      was obtained 20 days after the surgery. Coronary angiography demonstrated a
      saccular aneurysm (10 x 9 mm) originating at the distal segment of the left main
      coronary artery with 90% stenosis, and excellent patency of both saphenous vein
      grafts. Follow-up angiography was performed 1 and 3 years after the surgery. The
      size of the left main coronary aneurysm remained unchanged at both examinations.
      The patient did well with no further cardiac symptoms after 5 years.

PMID- 15584253
TI  - [Bilateral coronary ostial stenosis after aortic valve replacement with freestyle
      stentless bioprosthesis: a case report].
AB  - An 80-year-old woman underwent aortic valve replacement with Freestyle stentless
      prosthetic valve for the stenosis. Four months later, she was admitted with
      myocardial ischemia. Coronary angiography revealed severe stenosis in the ostium
      of both right and left coronary arteries. Coronary artery bypass grafting was
      performed. One year later, percutaneous coronary intervention was carried out for
      the bilateral coronary arteries because of unstable angina. Intravascular
      ultrasonography demonstrated localized, membranous, homogeneous, and severe
      stenoses in the ostium of the right and left coronary arteries. Histological
      examination of a specimen taken by directional coronary atherectomy showed
      intimal hypertrophy, mucinous degeneration, and hyaline degeneration without
      reactive change. There were no findings of atherosclerosis. These clinical,
      angiographical histological and intravascular ultrasonography findings suggest
      that the immunological reaction to the heterograft was the mechanism of the
      bilateral ostial coronary arteries stenoses in the present case. The possibility
      of immunological reaction after aortic valve replacement with heterograft should
      be considered. There have been no report on intravascular echocardiographic and
      histological findings.

PMID- 15584254
TI  - [A 21-year-old woman complaining of exertional shortness of breath].

PMID- 15584255
TI  - Effect of orthodontic forces on root resorption in molars submitted to
      experimental periodontitis.
AB  - The present experimental study addresses the issue of the development and size of
      root resorption areas in molars of rats submitted to orthodontic forces of 51 or
      75 g and the induction of periodontal disease by placing a cotton ligature around
      the cervix of the first upper molars for 48 hours. Immediately on removal of the
      ligature or 48 hs later we put an orthodontic device in place. The device
      comprised two steel bands. The arms of a helicoidal spring that exerted force
      towards palatine passed through the palatine tubes welded to the bands. The
      number of odontoclasts and the percentage of root resorption areas were
      determined histomorphometrically on bucco-palatine sections obtained at the level
      of the central roots. The data showed an increase in root resorption areas when
      the orthodontic forces were applied to molars of rats following the induction of
      periodontitis. The magnitude of the force was proportional to the size of the
      resorption areas and to the number of odontoclasts. Both these end-points
      exhibited smaller values when the forces were applied once the inflammatory
      reaction had subsided. The present study shows that the risk of development of
      root resorption areas in patients with periodontal disease submitted to
      orthodontic treatment would be lower if lighter forces were applied and treatment
      were delayed until the inflammatory signs have subsided.

PMID- 15584256
TI  - Histomorphometric evaluation of the effect of bovine collagen granules on bone
      healing. An experimental study in rats.
AB  - Collagen materials have been utilized in medicine and dentistry because of their
      proven biocompatibility and capability of promoting wound healing. The aim of the
      present experimental study was to perform a histomorphometric evaluation of the
      effect of bovine collagen granules on post-extraction alveolar wound healing in
      rats. Twenty male Wistar rats were submitted to bilateral extraction of the first
      lower molars under ketamine/xylazine anesthesia according to the technique
      previously described by Guglielmotti and Cabrini. Sterile Bovine collagen
      granules of approximately 80 +/- 10 microm (Membracel G, Lab. Celina, Buenos
      Aires) were hydrated with saline solution and placed into the right mesial socket
      (experimental side) with gentle pressure, completely filling the site. The
      contralateral sockets were considered as the control side. Sutures were not
      performed. After surgery neither special diet nor antibiotics were given. The
      rats were fed rat chow and water ad libitum. All the animals were killed on the
      30th day following surgery by ether overdose. The jaws were dissected,
      radiographed, decalcified, and embedded in paraffin. Sections were obtained at
      the level of the first molar mesial socket in a buccolingual orientation and
      stained with hematoxylin-eosin. The trabecular area and volume density of
      trabecular bone were measured histomorphometrically. The trabecular area was
      greater in alveoli treated with collagen granules than in control alveoli
      (P<0.05). Values of volume density of trabecular bone were greater in
      experimental than in control sockets (P<0.05). This experimental study provides
      evidence for the use of bovine collagen granules as bone grafting material, as a
      therapeutic alternative to fill postextraction sockets.

PMID- 15584257
TI  - Clinical and microbiological associations in chronic periodontitis.
AB  - Chronic Periodontitis is the most prevalent form of periodontal disease. The
      subgingival microflora has been associated with the onset and progression of the
      disease. The aim of this work was to establish associations and correlations
      between clinical indicators and subgingival plaque microbiological data in
      patients diagnosed with moderate or severe Periodontitis. One hundred sites with
      a probing depth of > or = 5 mm were selected. Plaque Index (PI), Gingival Index
      (GI), Bleeding on Probing (BP), Probing Depth (PD) and Clinical Attachment Level
      (CAL) were measured. The subgingival plaque microbiological assay comprised
      cultures in selective and non-selective media and identification tests for
      Porphyromonas gingivalis (Pg), Prevotella intermedia/nigrescens (Pi/n),
      Actinobacillus actinomycetemcomitans (Aa), Fusobacterium (F) and
      Peptostreptococcus micros (Pm). Dark field microscopy was used to analyze the
      relative proportions of Treponema to the total microbial morphotypes. Small
      Treponeina (ST), Medium Treponema (MT), Large Treponema (LT) and Total Treponema
      (TT) were determined. Our results showed associations and a correlation between
      PD and AL, r = 0.62 (p<.0001); PD and Pg X2 = 15.22, r = 0.39 (p<.001); AL and Pg
      X2 = 10.72, r = 0.32 (p<.001). A negative correlation was observed between Pg and
      Pi/n X2 = 12.65, r = -0.35 (p<.001); BP and F X2 = 8.93; GI and F X2 = 8.92. The
      present results reveal associations and correlations between some clinical
      indicators and subgingival plaque microorganisms in patients diagnosed with
      Chronic Periodontitis.

PMID- 15584258
TI  - Long-term sterility of orthodontic-surgical appliances.
AB  - The aim of this study was to evaluate the long-term sterility of new dental
      appliances according to the non rigid wrapping employed and assess the
      effectiveness of sterilization in a steam autoclave at 134 degrees for 20 minutes
      using physical, chemical, and biological indicators. All the experimental (E)
      samples and the control samples (C) were assigned to one of three groups
      according to the type of packaging: paper bag (E1), paper/plastic pouch (E2),
      nylon tubing bag (E3). Each bag contained standardized orthodontic wires and
      brackets and sterility indicators. The samples were evaluated at the following
      experimental times: immediately, and 6, 12, 24 and 30 months post-sterilization.
      The samples were analyzed under aerobic and anaerobic conditions in keeping with
      the protocol currently in use at the Department of Microbiology, School of
      Dentistry, University of Buenos Aires. The group of control, non-sterilized
      samples (C1, C2, C3) were analyzed prior to the onset of the study, and were
      found to be contaminated. None of the sterilized samples in any of the three
      experimental groups evidenced contamination at any of the experimental times. The
      results showed that, under the present conditions, the packages and orthodontic
      appliances remained sterile for 30 months. These results show the importance of
      controlling sterility and the storage conditions over time for all the
      orthodontic/surgical appliances used in invasive treatments.

PMID- 15584259
TI  - Oral health and salivary factors in rural schoolchildren.
AB  - The aim of the present study was to assess the association between some salivary
      factors and the oral health status of rural schoolchildren of Cordoba
      (Argentina). The study involved 19 students (aged 5-14 years) who attended 8
      rural schools of the region. We determined indices (r)dmf-t, (r)DMF-T and S-OHI.
      pH, salivary flow (vol/min), protein concentration, calcium and phosphate levels
      and the molar Ca/P ratio were evaluated in stimulated saliva. The arithmetic mean
      and standard error were assessed for each of the parameters. We employed the
      Principal Component Analysis (PCA) to assess the similarities and differences
      between salivary components for the splits (r)dmft = 0, (r)dmft > 0, (r)DMFT = 0
      and (r)DMFT > 0. We observed a positive correlation (Spearman's coefficient, p <
      or = 0.05) between the concentration of proteins, calcium, phosphate and salivary
      flow. The mean values for the salivary parameters evaluated evidence differences
      in the oral health status between the different schools under study. In five of
      the schools evaluated, the variables that best explain the condition of caries
      disease were concentration of proteins, calcium, phosphate, and the Ca/P molar
      ratio. The variation observed in the oral health indicators, volume/minute and
      salivary components between schools evidences the need to perform individual
      studies for each school and consider the needs and possibilities of each
      community when designing programs to promote oral health.

PMID- 15584260
TI  - Anatomic variations of the root canal of the rat according to age.
AB  - The mesial canal of the first lower molar of the rat has been used as an
      experimental model in Endodontics. The present study involves a detailed analysis
      of its structural variations as a function of age and thus contributes to its
      characterization and adequate use as an experimental model. We evaluated 60
      molars of Wistar rats of different body weight: (group 1: 300-399 g, n=22; group
      2: 400-499 g, n=16; group 3: 600-700 g, n=22). The samples were radiographed
      employing a standardized system. Total canal length and volume were measured on
      enlarged projections of the radiographs. Canal diameter was measured at coronary,
      middle and apical levels and employed to estimate the area of canal cross-section
      as an indicator of potential flow or metabolic interchange. From the second age
      group onwards, we detected radicular hypercementosis that increased canal length
      and resulted in the formation of a complex apical delta. The canal diameter
      decreased very significantly in the apical third. The estimated flow expressed in
      terms of the area of cross-section on the projection decreased from 1.2 mm2 in
      Group 1 to 0.05 mm2 in Group 2. Group 3 did not differ significantly from Group
      2. The present results reveal that the spontaneous, age-related variations in
      canal anatomy described herein must be considered when performing experimental
      endodontics in rats.

PMID- 15584261
TI  - Time-domain fiber laser hydrogen sensor.
AB  - We report a novel scheme for a fiber-optic hydrogen sensor based on an erbium
      doped fiber laser with a palladium-coated tapered fiber within the laser cavity.
      The tapered fiber acts as a hydrogen-sensing element. When the sensing element is
      exposed to a hydrogen atmosphere, its attenuation decreases, changing the cavity
      losses and leading to a modification of the laser transient. The hydrogen
      concentration is obtained by simple measurement of the buildup time of the laser.
      This technique translates the measurement of hydrogen concentration into the time
      domain, and it can be extended to many intensity-based fiber sensors. Relative
      variations in the buildup time of up to 55% at an increase of the hydrogen
      concentration from 0 to 10% are achieved with a resolution of better than 0.1%.

PMID- 15584262
TI  - Autosolitons in dispersion-managed systems with in-line saturable absorbers.
AB  - We study the formation of stable solitonlike pulses in dispersion-managed fiber
      transmission systems using an in-line fast saturable absorber. Operational
      regimes suitable for 40-Gbit/s channel rate transmission are demonstrated.

PMID- 15584263
TI  - Frequency metrology with a turnkey all-fiber system.
AB  - The repetition rate and carrier-envelope phase offset frequencies of a turnkey,
      all-fiber-based continuum generator were phase locked to a hydrogen maser. The
      frequency of the hydrogen maser was calibrated with a highly stable cesium atomic
      clock, and therefore a fully phase-locked optical frequency comb with well
      defined absolute frequencies was obtained. In contrast with the commonly used
      Ti:sapphire-laser-based systems, we have accomplished a fully turnkey system with
      no user-adjustable parts. To evaluate the performance of this novel system, we
      performed absolute frequency measurements in the telecommunications region and at
      1064 nm and compared them with our traditional Ti:sapphire-based comb.

PMID- 15584264
TI  - Photoerasure of ultraviolet-induced birefringence and polarization-mode
      dispersion of chirped fiber Bragg gratings.
AB  - The first, to my knowledge, experimental demonstration of photoerasure of UV
      induced birefringence and polarization-mode dispersion (PMD) in chirped fiber
      Bragg gratings is presented here. The photoerasure process carried out by
      launching high-peak-power (approximately 0.6-kW) pulsed (10-Hz, 5-ns) circularly
      polarized laser light in the visible wavelength (532 nm) through the core of a
      fiber with the grating was found to reduce its PMD by more than 85% to 0.12 ps.
      Possible reasons for the photoerasure process, including photobleaching of UV
      induced absorption and randomization of dipole orientation of UV-induced defects,
      are discussed.

PMID- 15584265
TI  - Photonic crystal fiber design for broadband directional coupling.
AB  - A novel design for a broadband directional coupler based on a photonic crystal
      fiber is investigated numerically. It is shown that suitable index-depressing
      doping of the core regions in an index-guiding twin-core photonic crystal fiber
      can stabilize the coupling coefficient between the cores over an extremely broad
      (octave-spanning) frequency range.

PMID- 15584266
TI  - Electrical fixing in near-stoichiometric lithium niobate crystals.
AB  - Photorefractive gratings are recorded in lithium niobate crystals in the presence
      of externally applied electric fields close to the coercive field. After optical
      erasure a voltage pulse above the poling threshold is applied, and by these means
      a photorefractive grating reappears that can be erased optically. The results
      point to electrical fixing, i.e., ferroelectric domain reversal induced by a
      space-charge field.

PMID- 15584267
TI  - High-contrast microscopy of semiconductor and metal sites in integrated circuits
      by detection of optical feedback.
AB  - High-contrast microscopy of semiconductor and metal sites in integrated circuits
      is demonstrated with laser-scanning confocal reflectance microscopy, one-photon
      (1P) optical-beam-induced current (OBIC) imaging, and detection of optical
      feedback by means of a commercially available semiconductor laser that also acts
      as an excitation source. The confocal microscope has a compact in-line
      arrangement with no external photodetector. Confocal and 1P OBIC images are
      obtained simultaneously from the same focused beam scanned across the sample
      plane. Image pairs are processed to generate exclusive high-contrast
      distributions of semiconductor, metal, and dielectric sites in a GaAs photodiode
      array sample.

PMID- 15584268
TI  - Quasi-group-velocity matching using integrated-optic structures.
AB  - We propose a device to compensate for group-velocity mismatch (GVM) effects that
      limit the efficiency-bandwidth product in nonlinear frequency-mixing devices.
      Integrated wavelength-dependent delay lines are introduced periodically in a
      waveguide containing a series of quasi-phase-matching (QPM) gratings. Appropriate
      choice of the time delays can compensate for GVM. We have demonstrated a two
      stage device in a periodically poled lithium niobate waveguide. Two approximately
      150-fs-long pulses generated 6 ps apart by second-harmonic generation in two QPM
      gratings were resynchronized by a fixed delay line, and their relative phase was
      fine controlled by temperature tuning. This technique, which can be iterated to
      more than two segments, permits optical frequency mixers with a higher efficiency
      bandwidth product than would be possible in a single grating short enough to
      avoid GVM effects.

PMID- 15584269
TI  - Bloch oscillations in optical dissipative lattices.
AB  - We show that Bloch oscillations are possible in dissipative optical waveguide
      lattices with a linearly varying propagation constant. These oscillations occur
      in spite of the fact that the Bloch wave packet experiences coupling gain and
      (or) loss. Experimentally, this process can be observed in different settings,
      such as in laser arrays and lattices of semiconductor optical amplifiers. In
      addition, we demonstrate that these systems can suppress instabilities arising
      from preferential mode noise growth.

PMID- 15584270
TI  - Three-dimensional optical trapping of partially silvered silica microparticles.
AB  - We demonstrate three-dimensional trapping of micrometer-diameter silica
      particles, partially coated with silver, within conventional optical tweezers.
      Although metallic particles are usually repelled from the beam focus by the
      scattering force, we show that transparent spheres partially coated with silver
      can be trapped with efficiencies comparable with dielectric particles. The
      trapping characteristics of these particles are examined as a function of
      metallic coverage, and the application of these particles to surface-enhanced
      resonance Raman scattering is investigated.

PMID- 15584271
TI  - Spectroscopy and continuous-wave diode-pumped laser action of Yb3+:YVO4.
AB  - The growth, spectroscopic properties, and laser performance of Yb:YVO4 crystal
      with laser diode pumping are reported. A peak absorption cross section of 7.4 x
      10(-20) cm2 at 985 nm, a radiative lifetime of 0.25 ms, and a stimulated-emission
      cross section of 1.25 x 10(-20) cm2 at 1008 nm for pi polarization were
      determined for the Yb3+ ions in YVO4. Continuous-wave laser action of Yb:YVO4 at
      1020-1027 nm was demonstrated with an output power of 610 mW and a slope
      efficiency of 49%.

PMID- 15584272
TI  - Repetition rate increase and diffraction-limited focal spots for a nonthermal
      equilibrium 100-TW Nd:glass laser chain by use of adaptive optics.
AB  - Dynamic wave-front correction is applied before each shot on a 100-TW, 30-J/300
      fs high-power laser facility by use of an adaptive-optics system. This system
      allows us to increase the repetition rate of high-energy lasers while maintaining
      excellent and constant beam focusability with a Strehl ratio of >0.75 despite the
      amplifiers' not being in thermal equilibrium. The best results in terms of the
      highest Strehl ratio and intensities are obtained when locking the system on wave
      front sensing after pulse recompression.

PMID- 15584273
TI  - Effect of chaos pass filtering on message decoding quality using chaotic external
      cavity laser diodes.
AB  - An experimental demonstration of the effect of chaos pass filtering on high
      frequency message transmission in the complete synchronization regime is
      reported. The opportunity for chaotic message decoding at frequencies up to 6 GHz
      is shown.

PMID- 15584274
TI  - Enhanced millimeter-wave transmission through subwavelength hole arrays.
AB  - We explore, both experimentally and theoretically, the existence in the
      millimeter-wave range of the phenomenon of extraordinary light transmission
      through arrays of subwavelength holes. We have measured the transmission spectra
      of several samples made on aluminum wafers by use of an AB Millimetre quasi
      optical vector network analyzer in the wavelength range 4.2-6.5 mm. Clear signals
      of the existence of resonant light transmission at wavelengths close to the
      period of the array appear in the spectra.

PMID- 15584275
TI  - Fourier phase microscopy for investigation of biological structures and dynamics.
AB  - By use of the Fourier decomposition of a low-coherence optical image field into
      two spatial components that can be controllably shifted in phase with respect to
      each other, a new high-transverse-resolution quantitative-phase microscope has
      been developed. The technique transforms a typical optical microscope into a
      quantitative-phase microscope, with high accuracy and a path-length sensitivity
      of lambda/5500, which is stable over several hours. The results obtained on
      epithelial and red blood cells demonstrate the potential of this instrument for
      quantitative investigation of the structure and dynamics associated with
      biological systems without sample preparation.

PMID- 15584276
TI  - Optoacoustic imaging with synthetic aperture focusing and coherence weighting.
AB  - Optoacoustic imaging takes advantage of high optical contrast and low acoustic
      scattering and has found several biomedical applications. In the common backward
      mode a laser beam illuminates the image object, and an acoustic transducer
      located on the same side as the laser beam detects the optoacoustic signal
      produced by thermoelastic effects. A cross-sectional image is formed by laterally
      scanning the laser beam and the transducer. Although the laser beam width is
      generally narrow to provide good lateral resolution, strong optical scattering in
      tissue broadens the optical illumination pattern and thus degrades the lateral
      resolution. To solve this problem, a combination of the synthetic aperture
      focusing technique with coherence weighting is proposed. This method synthesizes
      a large aperture by summing properly delayed signals received at different
      positions. The focusing quality is further improved by using the signal coherence
      as an image quality index. A phantom comprising hair threads in a 1% milk
      solution was imaged with an optoacoustic imaging system. The results show that
      the proposed technique improved lateral resolution by 400-800% and the signal-to
      noise ratio by 7-23 dB over conventional techniques.

PMID- 15584277
TI  - Detection of ultrasound-modulated photons in diffuse media using the
      photorefractive effect.
AB  - Ultrasound-modulated optical tomography is a dual-wave sensing technique in which
      diffusive light in a turbid medium interacts with an imposed acoustic field. A
      phase-modulated photon field emanates from the interaction region and carries
      with it information about the optomechanical properties of the medium. We present
      a technique for detection of ultrasound-induced optical phase modulation using an
      adaptive, photorefractive-crystal-based interferometry system. Experimental
      results are presented demonstrating detection of ultrasound-modulated signals in
      highly scattering media by use of pulsed ultrasound insonation.

PMID- 15584278
TI  - Jones matrix analysis for a polarization-sensitive optical coherence tomography
      system using fiber-optic components.
AB  - We present an analysis for polarization-sensitive optical coherence tomography
      that facilitates the unrestricted use of fiber and fiber-optic components
      throughout an interferometer and yields sample birefringence, diattenuation, and
      relative optic axis orientation. We use a novel Jones matrix approach that
      compares the polarization states of light reflected from the sample surface with
      those reflected from within a biological sample for pairs of depth scans. The
      incident polarization alternated between two states that are perpendicular in a
      Poincare sphere representation to ensure proper detection of tissue birefringence
      regardless of optical fiber contributions. The method was validated by comparing
      the calculated diattenuation of a polarizing sheet, chicken tendon, and muscle
      with that obtained by independent measurement. The relative importance of
      diattenuation versus birefringence to angular displacement of Stokes vectors on a
      Poincare sphere was quantified.

PMID- 15584279
TI  - Direct imaging through scattering media by use of efficient third-harmonic
      generation in organic materials.
AB  - We report on real-time, time-gated, direct imaging through scattering media with
      an attenuation of 14 mean-free paths by use of third-harmonic generation in the
      eye-safe and telecommunication-compatible near-IR spectral region (1550 nm).

PMID- 15584280
TI  - Experimental evaluation of an anisotropic scattering model of a slab geometry.
AB  - A model has been developed based on random walk theory that allows the diffusion
      of light along a principal axis to differ from that in orthogonal directions. We
      present expressions that describe the time-resolved intensity measured across a
      slab and on the surface of a semi-infinite medium for a principal axis oriented
      parallel or perpendicular to the surface. The model of time-resolved
      transmittance is compared with experimental data acquired by use of a phantom
      consisting of wax fibers arranged within a solid cube of resin. It is shown that
      a single set of optical parameters is sufficient to model the experimental
      measurements acquired across all three orientations of the cube.

PMID- 15584281
TI  - Miniaturized two-photon microscope based on a flexible coherent fiber bundle and
      a gradient-index lens objective.
AB  - We present a miniature, flexible two-photon microscope consisting of a fused
      coherent optical fiber bundle with 30,000 cores and a gradient-index lens
      objective. The laser focus of a standard two-photon laser-scanning microscope was
      scanned over the entrance surface of the fiber bundle, resulting in sequential
      coupling into individual cores. Fluorescent light was detected through the fiber
      bundle. Micrometer-sized fluorescent beads and pollen grains were readily
      resolved. In addition, fluorescently labeled blood vessels were imaged through
      the fiber bundle in rat brain in vivo.

PMID- 15584282
TI  - Multimode pumped continuous-wave solid-state Raman laser.
AB  - We demonstrate the continuous-wave operation of a solid-state Raman laser
      containing a barium nitrate crystal as the Raman medium. The Raman laser, which
      has a singly resonant cavity, is pumped by multimode radiation. The Raman
      oscillation threshold is reached at approximately 2 W of pump power. As much as
      500 kW/cm2 of Stokes power density at 60-kW/cm2 pump power density is obtained in
      the cavity.

PMID- 15584283
TI  - High-energy quasi-phase-matched optical parametric oscillation in a 3-mm-thick
      periodically poled MgO:LiNbO3 device.
AB  - We have demonstrated high-energy quasi-phase-matched optical parametric
      oscillation in a 3-mm-thick periodically poled 5-mol. % MgO-doped LiNbO3 device
      with a 32.1-microm grating period and a 30-mm length. With a large-spot-size pump
      laser of 2.2-mm diameter, we obtained a total output pulse energy of 22 mJ for
      both the signal (wavelength 1.82 microm) and the idler (2.56 microm) waves at an
      input pump energy of 46 mJ.

PMID- 15584284
TI  - High-average-power femtosecond pulse generation in the blue using BiB3O6.
AB  - Efficient generation of tunable femtosecond pulses in the blue is reported in the
      nonlinear crystal BiB3O6. By use of fundamental pulses from a mode-locked
      Ti:sapphire laser at 76 MHz, single-pass second-harmonic average powers of as
      much as 830 mW have been generated at 50% conversion efficiency, and a tunable
      range of 375-435 nm in the blue is demonstrated. Temporal measurements using
      cross correlation of the fundamental and second-harmonic pulses in a 100-microm
      thick beta-BaB2O4 crystal result in blue pulse durations of 220 fs for 130-fs
      fundamental pulses. Direct experimental comparison with beta-BaB2O4 confirms the
      superior performance BiB3O6 for second-harmonic generation of femtosecond pulses.

PMID- 15584285
TI  - Asymptotic characteristics of parabolic similariton pulses in optical fiber
      amplifiers.
AB  - The fundamental asymptotic nature of parabolic similariton pulses in normal
      dispersion fiber amplifiers is experimentally demonstrated. With frequency
      resolved optical gating characterization measurements with a fixed input pulse
      energy, the output parabolic pulse characteristics are shown to be invariant with
      the input pulse profile and duration and to be completely determined only by the
      amplifier parameters.

PMID- 15584286
TI  - Quantum-dot quantum-interference infrared design proposal photodetector: and
      modeling of performance characteristics.
AB  - A novel design of an IR photodetector operating at wavelengths around 10 microm
      is presented. It is based on a three-level quantum coherence effect in
      semiconductor quantum dots as measured in balanced-homodyne detection in a Mach
      Zehnder interferometer. The advantage of this design is the combination of room
      temperature operation and fast response time, whereas the major drawback is the
      high noise-equivalent power.

PMID- 15584287
TI  - Arbitrary structuring of two-dimensional photonic crystals by use of phase-only
      Fourier gratings.
AB  - The computer-generated holography technique is applied to the structuring of two
      dimensional (2D) photonic crystals with inherently embedded arbitrary defects.
      The technique uses phase-only Fourier gratings as a generator of spot arrays in
      the focal plane, such that a single exposure produces a 2D array of focused spots
      with desired defects or modifications in the lattice structure. We demonstrate
      several types of large-area 2D lattice structures with square, hexagonal, or
      hybrid lattices embedded with point and (or) line defects. Scanning the Fourier
      plane in the depth direction throughout multiphoton polymerization media allows
      3D lattices with stacked defect layers to be formed.

PMID- 15584288
TI  - Three-dimensional photonic crystal of negative refraction achieved by
      interference lithography.
AB  - A three-dimensional bicontinuous photonic crystal of a bcc lattice with all-angle
      negative refraction that can be achieved at optical frequencies by interference
      lithography is proposed. A numerical simulation of the focusing imaging of a slab
      of this crystal was performed to verify the property of all-angle negative
      refraction. The dependence of the negative-refraction frequency range on the
      threshold of photoresist development and on the dielectric constant is also
      discussed.

PMID- 15584289
TI  - Gradient-index narrow-bandpass filter fabricated with glancing-angle deposition.
AB  - Glancing-angle deposition (GLAD) is a fabrication method capable of producing
      thin films with engineered nanoscale porosity variations. GLAD can be used to
      create optical thin-film interference filters from a single source material by
      modification of the film refractive index through control of film porosity. We
      present the effects of introducing a layer of constant low density into the
      center of a rugate thin-film filter fabricated with the GLAD technique. A rugate
      filter is characterized by a sinusoidal refractive-index profile. Embedding a
      layer of constant refractive index, with a thickness equal to one period of the
      rugate index variation, causes a narrow bandpass to appear within the filter's
      larger stop band. Transmittance measurements of such a gradient-index narrow
      bandpass filter, formed with titanium dioxide, revealed an 83% transmittance peak
      at a vacuum wavelength of 522 nm, near the center of the stop band, with a FWHM
      bandwidth of 15 nm.

PMID- 15584290
TI  - Nonlinear polarization evolution of ultrashort pulses in microstructure fiber.
AB  - We present experimental and numerical results for nonlinear polarization
      evolution of femtosecond pulses during propagation in microstructure fiber.
      Numerical modeling shows that fiber dispersion permits a long interaction length
      between the components polarized along the two principal axes, thereby enhancing
      the effective nonlinear polarization evolution in microstructure fiber.

PMID- 15584291
TI  - Large-area broadband saturable Bragg reflectors by use of oxidized AlAs.
AB  - Broadband saturable Bragg reflectors (SBRs) are designed and fabricated by
      monolithic integration of semiconductor saturable absorbers with broadband Bragg
      mirrors. The wet oxidation of AlAs creates low-index AlxOy layers for broadband,
      high-index-contrast AlGaAs/AlxOy or InGaAlP/AlxOy mirrors. SBR mirror designs
      indicate greater than 99% reflectivity over bandwidths of 294, 466, and 563 nm
      for center wavelengths of 800, 1300, and 1550 nm, respectively. Highly strained
      and unstrained absorbers are stably integrated with the oxidized mirrors. Large
      scale lateral oxidation techniques permit the fabrication of SBRs with diameters
      of 500 microm. Large-area, broadband SBRs are used to self-start and mode lock a
      variety of laser systems at wavelengths from 800 to 1550 nm.

PMID- 15584292
TI  - Effect of charge ordering and disordering on terahertz radiation characteristics
      of magnetoresistive Pr0.7Ca0.3MnO3 thin films.
AB  - Terahertz (THz) radiation from voltage-biased photoswitching devices made on
      magnetoresistive manganite Pr0.7Ca0.3MnO3 have been investigated for thin films
      grown under different conditions. We find that the temperature dependence of THz
      radiation near the charge-ordering temperature strongly depends on the growth
      condition of Pr0.7Ca0.3MnO3, whereas THz radiation shows no such temperature
      dependence near the spin-ordering temperature.

PMID- 15584293
TI  - Nothing older than three years.

PMID- 15584294
TI  - Comment on the "More data required" editorial by Keith J. Halford (Ground Water
      42, no. 4: 477).

PMID- 15584295
TI  - Defining and managing sustainable yield.
AB  - Ground water resource management programs are paying increasing attention to the
      integration of ground water and surface water in the planning process. Many
      plans, however, show a sophistication in approach and presentation that masks a
      fundamental weakness in the overall analysis. The plans usually discuss issues of
      demand and yield, yet never directly address a fundamental issue behind the plan-
      how to define sustainable yield of an aquifer system. This paper points out a
      number of considerations that must be addressed in defining sustainable yield in
      order to make the definition more useful in practical water resource planning
      studies. These include consideration for the spatial and temporal aspects of the
      problem, the development of a conceptual water balance, the influence of
      boundaries and changes in technology on the definition, the need to examine water
      demand as well as available supply, the need for stakeholder involvement, and the
      issue of uncertainty in our understanding of the components of the hydrologic
      system.

PMID- 15584296
TI  - Comparison of single-domain and dual-domain subsurface transport models.
AB  - Subgrid modeling of some type is typically used to account for heterogeneity at
      scales below the grid scale. The single-domain model (SDM), employing field-scale
      dispersion, and the dual-domain model (DDM), employing local hydrodynamic
      dispersion and exchange between domains having large hydraulic conductivity
      contrasts, are well-known examples. In this paper, the two modeling approaches
      are applied to tritium migration from the H-area seepage basins to a nearby
      stream--Fourmile Branch--at the Savannah River Site. This location has been
      monitored since 1955, so an extensive dataset exists for formulating realistic
      simulations and comparing the results to data. It is concluded that the main
      parameters of both models are scale-dependent, and methods are discussed for
      making initial estimates of the DDM parameters, which include mobile/immobile
      porosities and the mass exchange coefficient. Both models were calibrated to
      produce the best fit to recorded tritium data. When various attributes of the
      dataset were considered, including cumulative tritium activity discharged to
      Fourmile Branch, plume arrival time, and plume attenuation due to closure of the
      seepage basins in 1988, the DDM produced results superior to the SDM, while
      causing no unrealistic upgradient dispersion. A sensitivity analysis showed that
      only the DDM was able to accurately produce both the instantaneous activity
      discharge and cumulative activity with a single parameter set. This is thought to
      be due to the advection-dominated nature of transport in natural porous media and
      the more realistic treatment of this type of transport in the DDM relative to the
      SDM.

PMID- 15584297
TI  - Important observations and parameters for a salt water intrusion model.
AB  - Sensitivity analysis with a density-dependent ground water flow simulator can
      provide insight and understanding of salt water intrusion calibration problems
      far beyond what is possible through intuitive analysis alone. Five simple
      experimental simulations presented here demonstrate this point. Results show that
      dispersivity is a very important parameter for reproducing a steady-state
      distribution of hydraulic head, salinity, and flow in the transition zone between
      fresh water and salt water in a coastal aquifer system. When estimating
      dispersivity, the following conclusions can be drawn about the data types and
      locations considered. (1) The "toe" of the transition zone is the most effective
      location for hydraulic head and salinity observations. (2) Areas near the
      coastline where submarine ground water discharge occurs are the most effective
      locations for flow observations. (3) Salinity observations are more effective
      than hydraulic head observations. (4) The importance of flow observations aligned
      perpendicular to the shoreline varies dramatically depending on distance seaward
      from the shoreline. Extreme parameter correlation can prohibit unique estimation
      of permeability parameters such as hydraulic conductivity and flow parameters
      such as recharge in a density-dependent ground water flow model when using
      hydraulic head and salinity observations. Adding flow observations perpendicular
      to the shoreline in areas where ground water is exchanged with the ocean body can
      reduce the correlation, potentially resulting in unique estimates of these
      parameter values. Results are expected to be directly applicable to many complex
      situations, and have implications for model development whether or not formal
      optimization methods are used in model calibration.

PMID- 15584298
TI  - Aquifer vulnerability to pesticide migration through till aquitards.
AB  - This study investigates the influence of key factors-mainly recharge rate and
      degradation half-life--on downward migration of the widely used pesticide
      mecoprop (MCPP) through a typical clayey till aquitard. The study uses the
      numerical model FRAC3Dvs, which is a three-dimensional discrete fracture/matrix
      diffusion (DFMD) numerical transport model. The model was calibrated with
      laboratory and field data from a site near Havdrup, Denmark, but the overall
      findings are expected to be relevant to many other sites in similar settings.
      Fracture flow and MCPP transport parameters for the model were obtained through
      calibration using well-characterized laboratory experiments with large (0.5 m
      diameter by 0.5 m high) undisturbed columns of the fractured till and a field
      experiment. A second level of upscaling and sensitivity analysis was then carried
      out using data on hydraulic head, fracture spacing, and water budget from the
      field site. The simulations of downward migration of MCPP show that MCPP
      concentration and mass flux into the underlying aquifer, and hence the aquifer
      vulnerability to this pesticide compound, is mainly dependent on the degradation
      rate of the pesticide, the overall aquitard water budget, and the ground water
      recharge rate into the aquifer. The influence of flow rate, matrix diffusion, and
      degradation rate are intertwined. This results in one to four orders of magnitude
      higher MCPP flux into the aquifer from aquifer recharge rates of 20 and 120
      mm/yr, respectively, for no degradation and MCPP half-life of 0.5 yr. From a
      sensitivity analysis it was found that the range of MCPP flux into the aquifer
      varied less than one order of magnitude due to (1) changing fracture spacing from
      1 to 10 m, or (2) preferential flow along inclined thin sand layers, which
      represent common conditions for the current and other settings of clayey till in
      Denmark and other glaciated areas in Europe and North America. The results
      indicate that for aquifers overlain by fractured clayey tills, the vulnerability
      to contamination with pesticides (pesticide flux into the aquifer) and other
      widespread agricultural contaminants is going to vary strongly in the watershed
      as a function of the distribution of aquitard water budget (flow rate) and
      aquitard redox environment (controlling contaminant degradation rates), even if
      the thickness of the till is relatively constant. DFMD modeling of cause-effect
      relationships within such systems has great potential to support decisions in
      planning, regulation, and contaminant remediation.

PMID- 15584299
TI  - Combining pump-and-treat and physical barriers for contaminant plume control.
AB  - A detailed analysis is presented of the hydraulic efficiency of plume management
      alternatives that combine a conventional pump-and-treat system with vertical,
      physical hydraulic barriers such as slurry walls or sheet piles. Various design
      settings are examined for their potential to reduce the pumping rate needed to
      obtain a complete capture of a given contaminated area. Using established
      modeling techniques for flow and transport, those barrier configurations
      (specified by location, shape, and length) that yield a maximum reduction of the
      pumping rate are identified assuming homogeneous aquifer conditions. Selected
      configurations are further analyzed concerning their hydraulic performance under
      heterogeneous aquifer conditions by means of a stochastic approach (Monte Carlo
      simulations) with aquifer transmissivity as a random space function. The results
      show that physical barriers are an appropriate means to decrease expected (mean)
      pumping rates, as well as the variance of the corresponding pumping rate
      distribution at any given degree of heterogeneity. The methodology presented can
      be transferred easily to other aquifer scenarios, provided some basic premises
      are fulfilled, and may serve as a basis for reducing the pumping rate in existing
      pump-and-treat systems.

PMID- 15584300
TI  - Environmental isotopes as indicators for ground water recharge to fractured
      granite.
AB  - To assess the contribution of accumulated winter precipitation and glacial
      meltwater to the recharge of deep ground water flow systems in fracture
      crystalline rocks, measurements of environmental isotope ratios, hydrochemical
      composition, and in situ parameters of ground water were performed in a deep
      tunnel. The measurements demonstrate the significance of these ground water
      recharge components for deep ground water flow systems in fractured granites of a
      high alpine catchment in the Central Alps, Switzerland. Hydrochemical and in situ
      parameters, as well as delta(18)O in ground water samples collected in the
      tunnel, show only small temporal variations. The precipitation record of
      delta(18)O shows seasonal variations of approximately 14% and a decrease of 0.23%
      +/- 0.03% per 100 m elevation gain. delta(2)H and delta(18)O in precipitation are
      well correlated and plot close to the meteoric water line, as well as delta(2)H
      and delta(18)O in ground water samples, reflecting the meteoric origin of the
      latter. The depletion of 18O in ground water compared to 18O content in
      precipitation during the ground water recharge period indicates significant
      contributions from accumulated depleted winter precipitation to ground water
      recharge. The hydrochemical composition of the encountered ground water, Na-Ca
      HCO3-SO4(-F), reflects an evolution of the ground water along the flowpath
      through the granite body. Observed tritium concentrations in ground water range
      from 2.6 to 16.6 TU, with the lowest values associated with a local negative
      temperature anomaly and anomalous depleted 18O in ground water. This demonstrates
      the effect of local ground water recharge from meltwater of submodern glacial
      ice. Such localized recharge from glaciated areas occurs along preferential
      flowpaths within the granite body that are mainly controlled by observed
      hydraulic active shear fractures and cataclastic faults.

PMID- 15584301
TI  - Hydraulics of recirculating well pairs for ground water remediation.
AB  - Recirculating well pairs are a proven means of implementing bioremediation and
      may also be useful for applying other in situ ground water remediation
      technologies. A bromide tracer test was performed to characterize the hydraulic
      performance of a recirculating well pair installed at Moffett Field, California.
      In particular, we estimate two important properties of the recirculating well
      pair: (1) the fraction of captured water that is recycled between the wells, and
      (2) the travel-time distribution of ground water in the induced zone of
      recirculation. We also develop theoretical estimates of these two properties and
      demonstrate they depend upon a dimensionless pumping rate, denoted xi. The
      bromide breakthrough curve predicted from theory agrees well with that determined
      experimentally at Moffett Field. The minimum travel time between the wells is
      denoted t(min). In theory, t(min) depends inversely on Q, the pumping rate in the
      recirculating wells, and is proportional to a2, the square of the distance
      between the wells. Both the experimental and theoretical travel-time
      distributions indicate that at least half the recirculating water travels between
      the wells along fast flowpaths (travel time < 2*t(min)). Therefore, when
      designing recirculating well pairs, engineers should ensure that t(min) will be
      sufficiently high to allow biologically mediated reactions (or other in situ
      remediation processes) sufficient time to proceed.

PMID- 15584302
TI  - Estimation of hydraulic conductivity in an alluvial system using temperatures.
AB  - Well water temperatures are often collected simultaneously with water levels;
      however, temperature data are generally considered only as a water quality
      parameter and are not utilized as an environmental tracer. In this paper, water
      levels and seasonal temperatures are used to estimate hydraulic conductivities in
      a stream-aquifer system. To demonstrate this method, temperatures and water
      levels are analyzed from six observation wells along an example study site, the
      Russian River in Sonoma County, California. The range in seasonal ground water
      temperatures in these wells varied from <0.2 degrees C in two wells to
      approximately 8 degrees C in the other four wells from June to October 2000. The
      temperature probes in the six wells are located at depths between 3.5 and 7.1 m
      relative to the river channel. Hydraulic conductivities are estimated by matching
      simulated ground water temperatures to the observed ground water temperatures. An
      anisotropy of 5 (horizontal to vertical hydraulic conductivity) generally gives
      the best fit to the observed temperatures. Estimated conductivities vary over an
      order of magnitude in the six locations analyzed. In some locations, a change in
      the observed temperature profile occurred during the study, most likely due to
      deposition of fine-grained sediment and organic matter plugging the streambed. A
      reasonable fit to this change in the temperature profile is obtained by
      decreasing the hydraulic conductivity in the simulations. This study demonstrates
      that seasonal ground water temperatures monitored in observation wells provide an
      effective means of estimating hydraulic conductivities in alluvial aquifers.

PMID- 15584303
TI  - Variations of bromide in potable ground water in the United States.
AB  - Concentrations of bromide in potable ground water that has <10 mg/L chloride
      range from 0.0032 to 0.058 mg/L with a median value of 0.016 mg/L. The
      chloride/bromide mass ratio for the same water ranges from 43 to 285 with a
      median value of 101. The ratios, which resulted from screening approximately 165
      analyses of water from 32 locations in 24 states in the United States, show a
      distinct geographic variation with highest values near the coast and trending
      toward a value of approximately 50 in the continental interior.

PMID- 15584304
TI  - Modeling multiaquifer wells with MODFLOW.
AB  - Multiaquifer wells, i.e., wells that are open across more than one aquifer, can
      have a profound effect on the hydraulics of a ground water system. These wells
      change the physical system by establishing direct hydraulic links between
      otherwise isolated strata. Several methods are available to simulate multiaquifer
      wells in the context of comprehensive ground water flow simulators. In this
      paper, we review four methods to represent multiaquifer wells with the widely
      used code MODFLOW. These methods include a specialized code developed, but never
      formally released, by the U.S. Geological Survey (USGS), the Multi-Aquifer Well
      (MAW1) Package. An expanded implementation of the techniques in the MAW1 Package
      has been incorporated in the Multi-Node Well Package released recently by the
      USGS (Halford and Hanson 2002). We examine the performance of the methods in the
      context of a benchmarking study against the analytical solutions of Papadopulos
      (1966) and Sokol (1963). Our results demonstrate that results obtained with the
      MAW1 Package closely match exact solutions for pumping and nonpumping conditions,
      using both coarse and refined grids.

PMID- 15584305
TI  - Matching solute breakthrough with deterministic and stochastic aquifer models.
AB  - Two different deterministic and two alternative stochastic (i.e., geostatistical)
      approaches to modeling the distribution of hydraulic conductivity (K) in a
      nonuniform (sigma2ln(K)) = 0.29) glacial sand aquifer were used to explore the
      influence of conceptual model selection on simulations of three-dimensional
      tracer movement. The deterministic K models employed included a homogeneous
      effective K and a perfectly stratified 14 layer model. Stochastic K models were
      constructed using sequential Gaussian simulation and sequential i ndicator
      simulation conditioned to available K values estimated from measured grain size
      distributions. Standard simulation software packages MODFLOW, MT3DMS, and MODPATH
      were used to model three-dimensional ground water flow and transport in a field
      tracer test, where a pulse of bromide was injected through an array of three
      fully screened wells and extracted through a single fully screened well
      approximately 8 m away. Agreement between observed and simulated transport
      behavior was assessed through direct comparison of breakthrough curves (BTCs) and
      selected breakthrough metrics at the extraction well and at 26 individual
      multilevel sample ports distributed irregularly between the injection and
      extraction wells. Results indicate that conceptual models incorporating formation
      variability are better able to capture observed breakthrough behavior. Root mean
      square (RMS) error of the deterministic models bracketed the ensemble mean RMS
      error of stochastic models for simulated concentration vs. time series, but not
      for individual BTC characteristic metrics. The spatial variability models
      evaluated here may be better suited to simulating breakthrough behavior measured
      in wells screened over large intervals than at arbitrarily distributed
      observation points within a nonuniform aquifer domain.

PMID- 15584306
TI  - A critical analysis of the cumulative rainfall departure concept.
AB  - Evaluation of trends in time-series, such as precipitation or ground water
      levels, is an essential element in many hydrologic evaluations, including water
      resource studies and planning efforts. The cumulative rainfall departure (CRD)
      from normal rainfall is a concept sometimes utilized to evaluate the temporal
      correlation of rainfall with surface water or ground water levels. Permutations
      of the concept have been used to estimate recharge or aquifer storativity, and in
      attempts to explain declining ground water levels. The cumulative departure
      concept has hydrologic meaning in the short term, as a generalized evaluation of
      either meager or abundant rainfall, and when utilized in connection with a
      detailed water budget analysis can be used in a predictive fashion. However, the
      concept can be misapplied if extended over lengthy periods. Misapplication occurs
      because of several factors including the separation of the mean and median in
      nonnormal distributions, how the choice of beginning and end points of the data
      can affect the results, the lack of consideration that above-average rainfall can
      reset the hydrologic system without mathematically eliminating the accumulated
      deficit, and the lack of support for the necessary inference that rainfall events
      and hydrologic levels widely separated in time are linked. Standard statistical
      techniques are available to reliably determine trends and can provide rigorous
      statistical measures of the significance of conclusions. Misuse of the CRD
      concept can lead to erroneous and unsupported conclusions regarding hydrologic
      relationships and can potentially result in misguided water resource decision
      making.

PMID- 15584307
TI  - Noise in pressure transducer readings produced by variations in solar radiation.
AB  - Variations in solar radiation can produce noise in readings from gauge pressure
      transducers when the transducer cable is exposed to direct sunlight. This noise
      is a result of insolation-induced heating and cooling of the air column in the
      vent tube of the transducer cable. A controlled experiment was performed to
      assess the impact of variations in solar radiation on transducer readings. This
      experiment demonstrated that insolation-induced fluctuations in apparent pressure
      head can be as large as 0.03 m. The magnitude of these fluctuations is dependent
      on cable color, the diameter of the vent tube, and the length of the transducer
      cable. The most effective means of minimizing insolation-induced noise is to use
      integrated transducer-data logger units that fit within a well. Failure to
      address this source of noise can introduce considerable uncertainty into analyses
      of hydraulic tests when the head change is relatively small, as is often the case
      for tests in highly permeable aquifers or for tests using distant observation
      wells.

PMID- 15584308
TI  - A procedure for automated analysis of brief pumping tests of domestic wells.
AB  - A new computer program has been developed to automate analysis of brief single
      well pumping tests. Adapted from a procedure developed by Picking (1994) that
      does not require measurement of the pumping rate, this new program is menu-driven
      and eliminates one significant source of imprecision in Picking's original
      method, namely, selection of "well function of u" values by interpolation in a
      lookup table. This new program has been applied to tests of 25 domestic wells
      penetrating bedrock, each pumped for <2 min.

PMID- 15584309
TI  - Hydrogeology: a short history, part 2.

PMID- 15584310
TI  - A review of the effects of breastfeeding on respiratory infections, atopy, and
      childhood asthma.
AB  - The etiology of childhood asthma is not fully understood. Early exposure to
      certain respiratory infections may be protective for atopy and/or asthma whereas
      some infections have been suggested to exert the opposite effects. Wheezing lower
      respiratory illness (LRI) in the first year of life and atopy are independently
      associated with increased risk for current asthma in childhood and their effects
      are mediated via different causal pathways. These risk factors are multiplicative
      when they operate concommitantly within individual children. Exclusive
      breastfeeding protects against asthma via effects on both these pathways, as well
      as through other as yet undefined mechanisms. Furthermore, exclusive
      breastfeeding may protect against asthma and may reduce the incidence of lower
      respiratory illness, especially respiratory syncytial virus (RSV). We have
      previously demonstrated a protective effect of exclusive breastfeeding on
      asthmatic traits in children. The aim of this review was to clarify this
      protective association from intermediate associations with respiratory
      infections, atopy, or through other facets of breastfeeding. The bioactivity of
      breast milk and subsequent pathways that may act upon the development of asthma
      in children are explored.

PMID- 15584311
TI  - Asthma severity: the patient's perspective.
AB  - BACKGROUND: Although asthma is a common condition, limited epidemiological data
      exists on the distribution or course of asthma severity. We know even less about
      how patients or parents rate the severity of their or their child's asthma or
      what factors they associate with more severe asthma. A large nationally diverse
      sample of asthma patients' self-assessment of severity is available but has not
      been analyzed to look at asthma severity from the patients' perspective. METHOD:
      Data from the "household" and "event" files from the 1999 Medical Expenditure
      Panel Survey were combined to obtain a distribution of patient-reported asthma
      severity and the health care utilization, medication usage, and personal
      characteristics associated with different levels of self-reported severity for
      that subgroup that answered the chronic disease portion of the survey. RESULTS:
      Almost two thirds of patients (63% of adults) or parents (65% of children)
      described their or their child's asthma as very or somewhat serious. Among both
      children and adults, more severe asthma was associated with greater numbers of
      missed school and workdays, and lower overall health status. The associated
      differences in health utilization varied by age. Models of severity based on
      available NAEPP criteria explained less than 10% of the participant's variation
      in self-reported asthma severity. CONCLUSION: Parents and patients with asthma
      appear to use different metrics than physicians and researchers to define the
      more severe categories of asthma. This disparity suggests the need for an asthma
      measure that is more widely understood, and accepted by patients and clinicians
      to serve as a tool to improve asthma-related communications and the achievement
      of mutually determined therapy goals.

PMID- 15584312
TI  - Airway remodeling: a comparison between fatal and nonfatal asthma.
AB  - BACKGROUND: Airway remodeling has been recently one of the main goals in asthma
      research because it has been implicated to influence airway behavior and
      evolution of asthma; hence, important in long-term followup of asthmatic
      patients. METHODS: Airways of fatal asthma (n=3), non-fatal asthma (n=3) and
      control cases (n=4) were studied using morphometry and immunohistochemical and
      H&E staining. RESULTS: The basement membrane was thicker in the cartilaginous and
      membranous airways of fatal and non-fatal asthma groups compared to the control
      group (p<0.05). Smooth muscle shortening was greater in airways of fatal asthma
      cases while submucosal gland area and mucus plug occupying ratio were greater in
      fatal asthma large airways compared to the two other groups (p<0.01). Increased
      intact and degranulated mast cells were observed in smooth muscle and in
      submucosal gland of fatal asthma airways (p<0.01) and were associated with
      greater degree of smooth muscle shortening and larger submucosal gland area,
      respectively. Eosinophil and EG2+ cell infiltrations were greatest in lamina
      propria of airways of fatal asthma than in nonfatal and control cases (p<0.01),
      but were not associated with any airway structural change. CONCLUSION: Increased
      infiltration of eosinophils in the lamina propria and mast cells in smooth muscle
      and submucosal glands may have a role in airway remodeling of fatal asthma
      airways but needs further investigation. Moreover, mast cells in cartilaginous
      airways may participate in the regulation of smooth muscle tone and mucous gland
      secretion and hyperplasia.

PMID- 15584313
TI  - Myeloperoxidase release after allergen-specific conjunctival challenge.
AB  - BACKGROUND: Allergen-specific conjunctival challenge is a fruitful and complete
      tool in evaluating pathophysiological phenomena of allergic inflammation. After
      challenge, a significant neutrophil infiltrate occurred in allergic subjects. The
      primary (azurophilic) granules of neutrophils contain a variety of enzymes that
      might potentiate inflammation, such as myeloperoxidase (MPO). It is not known
      whether allergen-specific conjunctival challenge (ASCC) is able to elicit MPO
      release. We also investigated the possible role of immunotherapy (IT) in the
      release of MPO. METHOD: The groups studied included Dactylis glomerata-sensitive
      adult atopic patients suffering from seasonal allergic rhinoconjunctivitis, and
      healthy adult nonatopic volunteer controls. One group of allergic patients
      received no specific hyposensitization (not-IT allergic group). A second group of
      allergic patients had been immunotherapy-treated with Dactylis glomerata extract
      for the preceding three years and continued to receive a maintenance dose within
      the highest potency of the extract (IT-allergic group). ASCC with Dactylis
      glomerata was performed outside the pollen season in all subjects.
      Myeloperoxidase was assayed by MPO-enzyme immunoassay method. RESULTS: Thirty
      minutes after challenge, myeloperoxidase levels in the non-immunotherapy allergic
      patients were significantly higher compared than in the healthy group (p<0.001).
      The levels of myeloperoxidase released in the immunotherapy allergic group were
      significantly lower than those in the nonimmunotherapy allergic group (p<0.001)
      and higher than those in nonallergic subjects (p<0.001). CONCLUSION: These
      results indicate that after ASCC there is a release of MPO. Our study suggests
      that immunotherapy actively modifies the release of MPO after ASCC.

PMID- 15584314
TI  - The impact of childhood asthma on parental quality of life.
AB  - Measuring the quality of life of caregivers is important for interventions
      designed for young children with asthma. However, little is known about the
      impact of childhood asthma on parental quality of life for certain subgroups.
      This study included the families of young urban children with mild persistent to
      severe persistent asthma. The goal was to evaluate the relationship between
      caregivers' quality of life and the children's asthma severity, and to consider
      the influence of sociodemographic factors on the caregivers' quality of life.
      Children age 3-7 years (63% male, 59% Black, 75% Medicaid), with mild persistent
      to severe persistent asthma, were identified from a school-based screening
      survey. Caregiver quality of life was assessed at baseline and at the end of the
      study using the Paediatric Asthma Caregiver's Quality of Life Questionnaire
      (PACQLQ). Pearson correlation coefficients were used to assess the relationship
      between the PACQLQ and parent-reported asthma symptoms during the same time
      period. For all measures of severity, there was a significant correlation with
      quality of life (range r=0.23-0.51, all p<.01). Improvements in the PACQLQ
      correlated with decreases in symptom scores including symptom days (r=-0.27,
      p<.001) and symptom nights (r=-0.22, p=.005). In a multivariate model, Hispanic
      ethnicity, the use of daily maintenance medications, and exposure to secondhand
      smoke independently predicted worse quality of life scores. We conclude that the
      caretaker's quality of life, as assessed by the PACQLQ, is directly influenced by
      the child's asthma severity as well as other family factors among a group of
      young urban children with significant asthma.

PMID- 15584315
TI  - Preventive therapy for asthmatic children under Florida Medicaid: changes during
      the 1990s.
AB  - BACKGROUND: In response to the increasing prevalence and severity of asthma in
      this country, the National Institutes of Health in 1991 published an expert
      consensus report Guidelines for the Diagnosis and Management of Asthma. An
      important aspect of the report included the recommendation that children with
      moderate asthma may benefit from daily treatment with anti-inflammatory drugs
      such as inhaled corticosteroids and cromolyn. OBJECTIVES: The objective of this
      article is to examine changes in prescribing of daily anti-inflammatory drugs for
      children covered by Florida Medicaid during two 2-year periods, the first just
      after publication of the Guidelines and the second 7 years later; and to estimate
      adherence to treatment by children who received one of them. DESIGN: The study
      groups for each of the two 2-year periods included only children 2 to 18 years
      old who had medical or institutional claims to Medicaid for asthma and who were
      continuously covered during the period. From outpatient claims files, a record
      was assembled for each child containing the number of prescriptions in each
      category of asthma drugs during each interval. For each child who had received a
      prescription for any daily preventative drug, the number of such prescriptions
      and the time after the first were used to calculate availability of medication.
      RESULTS: The proportion of children receiving at least one prescription for a
      preventive drug rose from 26.9 per cent of children in 1990-1992 to 52.6 per cent
      in 1997-1998. African-American children were less likely to receive a preventive
      in the earlier period, but the difference narrowed by 1997. Assuming that one
      refill provided a month's supply of drug, the percentage of children who had
      enough drug dispensed to treat for more than half of the time following the
      initial prescription rose from 6.1 to 11.2 per cent. For children with the
      highest use of beta-agonist (11 or more prescriptions over 2 years), the
      percentage rose from 25.3 to 35.8; in those with 5 or more courses of a systemic
      steroid, the proportion rose from 36.6 to 40.2. During the second interval,
      adherence to use of oral montelukast was no better than to inhaled daily
      medications. CONCLUSION: In the 7 years after the publication of the NIH
      Guidelines, asthmatic children covered by Florida Medicaid had an approximate
      doubling in the proportion who received a prescription for a daily anti
      inflammatory drug. However, during both intervals the adherence to treatment once
      prescribed remained low even among those with the severest asthma. Effective
      strategies to improve adherence will be needed before these drugs can realize
      their potential.

PMID- 15584316
TI  - Measuring adherence with the Doser CT in children with asthma.
AB  - Non-adherence with prescribed asthma treatment causes compromised treatment
      effectiveness, including greater morbidity, mortality, and health care
      utilization costs. As a result, there is an increasing interest in measuring
      patient adherence behaviors. Electronic monitoring devices offer a promising
      method for assessing patient adherence behavior patterns. The reliability of the
      Doser Clinical Trials (CT) (Meditrack Products, Hudson, MA), an inexpensive,
      pressure-actuated device that monitors metered-dose inhaler (MDI) usage, was
      evaluated in a field study of outpatient pediatric asthmatics. Canister weight
      and various Doser CT measures of patient medication use were compared to
      determine the reliability and usefulness of the device. Doser CTs were dispensed
      to 16 research subjects for use on corticosteroid MDIs over a period of several
      months. One Doser CT per month was dispensed to each subject. Doser CTs were
      collected at 30-60 day intervals, with a total of 61 months of Doser CT data
      obtained across the subjects. MDI canister weights were monitored for a subset of
      6 subjects. Usable Doser CT data were summarized and average adherence estimates
      were computed. Adherence estimates differed from one another and the adherence
      estimate, as measured by canister weight, was significantly higher than each
      Doser CT estimate. However, overall, the Doser CT showed adequate reliability as
      evidenced by high correlations among the Doser CT estimates of adherence and the
      existing gold standard of canister weight. The Doser CT is likely to be useful
      for monitoring MDI use in clinical care and research, potentially providing
      greater accuracy than the standard of canister weight.

PMID- 15584317
TI  - Airway reactivity is a determinant of bronchodilator responsiveness after
      methacholine-induced bronchoconstriction.
AB  - Airway hyperresponsiveness (AHR) is one of the characteristics of asthma and a
      risk factor for persistent airflow limitation. Poor response to bronchodilator
      may be a cause of persistent airflow limitation. Multiple factors may determine
      bronchodilator responsiveness, including airway reactivity to nonspecific
      bronchoconstrictive agents. If patients with AHR have poor bronchodilator
      responsiveness, then it could be a potential mechanism for asthma and persistent
      airflow limitation in these patients. The objective of this study is to assess
      the relationship between airway reactivity to methacholine and responsiveness to
      beta-agonist and beta-agonist/anticholinergic combination in a large subject
      population. A retrospective data analysis was undertaken of 764 consecutive
      subjects with > or = 20% reduction in forced expiratory volume during the first
      second of exhalation from total lung capacity (FEV1) after < or = 189 cumulative
      units of methacholine. The first 382 subjects received 3 inhalations of
      metaproterenol and the second 382 subjects received 3 inhalations of albuterol
      and ipratropium combination after > or = 20% reduction in FEV1. Bronchodilator
      responsiveness was measured as the percent increase in FEV1 after the treatment.
      Airway reactivity was assessed as the log10 of methacholine dose response slope.
      In a simple linear regression model, airway reactivity was significantly related
      to bronchodilator responsiveness. The coefficient of determination (r2) was 0.15
      for the whole groups; 0.14 for metaproterenol group and 0.18 for
      albuterol/ipratropium combination group (all p<0.0001). The regression
      coefficient (beta) was 14.0 for the whole group; 14.8 and 13.2, respectively, for
      the two bronchodilator groups. Airway reactivity to methacholine is a determinant
      of airway responsiveness to both beta-agonist and beta-agonist/anticholinergic
      combination. Subjects with higher airway reactivity have higher bronchodilator
      responsiveness.

PMID- 15584318
TI  - High levels of cord serum eosinophil cationic protein predict the risk of atopy.
AB  - BACKGROUND: Transient tachypnoea of the newborn is a transient respiratory
      disturbance characterized by tachypnoea shortly after birth, which resolves
      within 2 to 5 days. The basic pathogenetic mechanism is the delayed resorption of
      the alveolar fluid of which the exact triggering mechanism still remains unknown.
      An etiological link associated with parenteral history of atopy was proposed by
      several studies. Some laboratory studies also revealed that serum IgE, eosinophil
      cationic protein (ECP) and cord IgE were higher among infants with maternal
      history of atopy. OBJECTIVE: The purpose of this study was to investigate the
      possible association of parental history of atopy with cord blood ECP and IgE
      concentrations in infants with transient tachypnoea of the newborn. METHODS: ECP
      and IgE levels were quantified in cord blood samples of 30 infants who were
      diagnosed as having transient tachypnoea of the newborn. The control group (N=30)
      was selected among healthy newborns with similar birth weight and gestational
      age. RESULTS: Cord blood ECP concentrations were significantly higher in the
      study group (17.6 microg/L) than in healthy control subjects (7.89 microg/L). In
      addition, transient tachypnoea of the newborn was more frequent in infants with a
      family history of atopic disease (p<0.01). Cord blood IgE concentrations were
      also higher in the study group than the controls (4.1 versus 3.28 mg/L) but the
      difference was not statistically significant (p>0.05). CONCLUSION: Family history
      of atopy and elevated levels of cord blood ECP are risk factors for transient
      tachypnoea of the newborn. In addition cord blood ECP level is a useful marker
      for predicting the risk of atopy.

PMID- 15584319
TI  - Toward a doctor-patient partnership.

PMID- 15584320
TI  - Cognitive behavioural therapy.

PMID- 15584321
TI  - Otitis media.

PMID- 15584322
TI  - Prescribing in older people.

PMID- 15584323
TI  - Current status of hormone therapy in general practice in Australia.
AB  - The BEACH program is a continuous national study of general practice activity in
      Australia. The subject of this analysis was all problems for which a hormone
      therapy years (HT) medication was prescribed or supplied at HT encounters with
      women aged 40 and over between March 2002 and April 2004. This provides a
      backdrop against which the theme articles in this issue of Australian Family
      Physician can be further considered.

PMID- 15584324
TI  - Hormone therapy--weighing up the evidence.
AB  - BACKGROUND: Hormone therapy (HT) use is well established for menopausal symptom
      relief, but its use is not currently considered justified for the prevention of
      disease. OBJECTIVE: This article reviews the recent literature on the risks and
      benefits of HT in postmenopausal women. DISCUSSION: Menopausal symptoms are
      severe in around 20% of Australian women and HT effectively relieves these
      symptoms. Controversy still surrounds the risk profile of HT in women at the time
      of the menopausal transition, although risks are likely to be small. Recent
      literature has demonstrated that the role of HT in disease prevention is limited,
      based primarily on the lack of preventive benefits rather than on the small but
      present adverse effects of HT use. Historically, the HT literature holds many
      salient lessons for clinicians. These include the shortcomings of animal data,
      observational human data, and human trials focussing on intermediate end-points
      in guiding clinical practice. The HT story also reinforces the principle that
      health prevention strategies in low risk primary prevention settings should be
      lifestyle based. Pharmacological therapy, with its inherent risks, even if small,
      should be reserved for high risk settings.

PMID- 15584325
TI  - Assessment of women in midlife.
AB  - BACKGROUND: Midlife is much more than menopause. At the time of their life when
      women may be experiencing symptoms relating to decreased ovarian function, they
      are also confronted with a range of physical and psychosocial issues that may
      affect their wellbeing. OBJECTIVE: This article outlines the range of clinical
      presentations of women in midlife and discusses assessment of these presentations
      in the context of the individual woman's life. DISCUSSION: Women in midlife
      present to doctors for a variety of reasons including information and preventive
      health, vasomotor or other symptoms of oestrogen deficiency, menstrual disorders,
      breast disorders, sexual difficulty, relationship and family issues, or mood
      disorders. Forming an effective doctor-patient partnership to address these
      issues requires time, empathy, good interpersonal skills, comprehensive and
      sensitive history taking and examination skills, and a good knowledge of relevant
      research.

PMID- 15584326
TI  - Is this menopause? Women in midlife--psychosocial issues.
AB  - BACKGROUND: Psychosocial influences have been found to impact on the symptoms a
      woman may experience as she moves through the menopause transition. Consequently
      any assessment of the menopausal woman should include an exploration and
      understanding of how the many psychosocial factors influence the experience of
      menopause and midlife. OBJECTIVE: This article describes the many psychosocial
      factors that influence the experience of menopause including midlife issues, role
      and purpose in life, interpersonal relationships, libido, personality,
      psychological history and present psychological functioning, body image and
      sociocultural issues. Case studies are included to illustrate the importance of
      including psychosocial factors in the assessment and treatment of the menopausal
      woman. DISCUSSION: Any assessment of the menopause experience should include
      psychosocial influences and the context of women's lives. In a consultation where
      both the physical and psychosocial issues are explored, we come closer to
      addressing the true needs of each patient.

PMID- 15584327
TI  - If not hormones--then what?
AB  - BACKGROUND: The Women's Health Initiative study has made women reconsider their
      use of hormone therapy and made medical practitioners review the risks and
      benefits to each patient. The significance of lifestyle, nonprescription, and
      prescription therapies for menopause management are of increasing relevance.
      OBJECTIVE: This article reports on the evidence from randomised controlled
      clinical trials and population based cohorts on nonhormonal management of
      menopause symptoms and on the role of diet and exercise in osteoporosis
      prevention. Personal tips are included. DISCUSSION: Menopausal consultations
      should include a discussion of diet and exercise, and education of available over
      the-counter therapies. For those women in whom oestrogen is contraindicated,
      prescriptions of serotonin noradrenergic reuptake inhibitors or clonidine may be
      indicated.

PMID- 15584328
TI  - Menopause--a treatment algorithm.

PMID- 15584329
TI  - Menopause forum--a case discussion on midlife issues.
AB  - The authors of our theme articles this month discuss their approach to the
      assessment and management of a woman presenting with issues relating to menopause
      and midlife.

PMID- 15584330
TI  - Dysfunctional uterine bleeding.
AB  - BACKGROUND: Dysfunctional uterine bleeding (DUB) is the major cause of heavy
      menstrual bleeding and impacts on women's health both medically and socially.
      OBJECTIVE: This article reviews the management of DUB. DISCUSSION: Dysfunctional
      uterine bleeding is defined as heavy menstrual uterine bleeding not due to any
      recognisable cause and is therefore a diagnosis of exclusion. Other conditions
      such as uterine fibroids, endometrial polyps and systemic diseases should be
      excluded by appropriate investigations. In the adolescent, investigations for a
      coagulopathy should be performed. The pathophysiology of DUB is largely unknown
      but occurs in both ovulatory and anovulatory menstrual cycles. Medical treatments
      include nonsteroidal anti-inflammatory drugs or antiprostaglandins, tranexamic
      acid, the progestogen releasing intrauterine device, combined oral contraceptive
      pills, and other hormonal therapies. As no medical treatment is superior to
      another, each woman should be individually assessed as to appropriate management.
      Surgical treatments include endometrial ablation and hysterectomy.

PMID- 15584331
TI  - Guidelines for the management of postmenopausal osteoporosis for GPs.
AB  - BACKGROUND: Since the last series of guidelines on the management of osteoporosis
      from Osteoporosis Australia was published in Australian Family Physician (October
      2002), there have been further advances in our understanding of the treatment
      involved in both the prevention of bone loss and the management of established
      osteoporosis. OBJECTIVE: This article provides updated guidelines for the
      management of postmenopausal osteoporosis to assist general practitioners
      identify those women at risk, and reviews current treatment strategies.
      DISCUSSION: Osteoporosis and its associated problems are major health concerns in
      Australia, especially with an aging population. While important principles of
      management are still considered to be maximising peak bone mass and preventing
      postmenopausal bone loss, new clinical trial data about drugs such as the
      bisphosphonates, raloxifene and oestrogen have recently become available and the
      relative role of various agents is gradually becoming clearer. The use of long
      term hormone therapy has mixed risks and benefits that requires individual
      patient counselling.

PMID- 15584332
TI  - Benzodiazepine dependence.
AB  - BACKGROUND: Benzodiazepine dependency can occur as a result of treatment for
      anxiety disorders or sleep disturbance. While benzodiazepine withdrawal can be
      challenging, cessation of use can be even more difficult if there are other
      comorbidities such as oestrogen deficiency with vasomotor symptoms and anxiety
      disorders. OBJECTIVE: This article provides practical information for general
      practitioners in the management of patients with benzodiazepine dependence.
      DISCUSSION: Some patients may have common medical presentations and coexisting
      drug dependence. It is often difficult to separate these two issues. In the case
      of benzodiazepine dependence, gradual withdrawal over time and nonpharmacological
      treatment of the symptoms of withdrawal such as anxiety or insomnia is effective.
      Better outcomes are achieved where the GP discusses and plans strategies well in
      advance with the patient. Treatment often involves multiple interventions from
      various health professionals. General practitioners are ideally placed to
      coordinate such treatment.

PMID- 15584333
TI  - Writing a police statement.
AB  - BACKGROUND: Requests for police statements regarding a patient's medical
      condition or injuries are common. A lack of training in their preparation,
      coupled with ignorance as to their fate, combine to make the task one which is
      generally viewed as a necessary paperwork evil. OBJECTIVE: This article aims to
      provide practical guidelines and a suggested format for use when preparing a
      police statement. DISCUSSION: Police statements prepared by medical practitioners
      are important documents whose intended audience is overwhelmingly nonmedical. A
      small time investment made in the preparation of a concise, objective report in
      language likely to be understood by the lay person will assist the courts in
      understanding complex medical issues and may obviate the need for the doctor to
      appear in court as a witness. A structured statement 'proforma' can be readily
      customised and will both reduce time in preparation of reports and serve as a
      prompt for inclusion of essential details.

PMID- 15584334
TI  - Dry eyes, menopause and hormone therapy. Eye series--21.

PMID- 15584335
TI  - Clinical guidelines: breast cancer.
AB  - Case histories are based on actual medical negligence claims, however, certain
      facts have been omitted or changed by the author to ensure the anonymity of the
      parties involved. Failure to diagnose breast cancer is a relatively common cause
      of complaints and claims involving general practitioners. This article examines
      the use of evidence based clinical guidelines and outlines some risk management
      strategies for GPs to minimise the possibility of a complaint or claim arising
      from an allegation of failure to diagnose breast cancer.

PMID- 15584336
TI  - Changing attitudes to 'the change'.
AB  - BACKGROUND: In order to practice efficiently, experienced doctors use heuristics
      (decision making shortcuts). In most cases decision making shortcuts improve the
      service we offer, allowing us to make appropriate decisions more quickly.
      However, occasionally shortcuts can mislead. It is important to reflect on the
      shortcuts we use so as to reduce the risk of mistakes. OBJECTIVE: This article
      examines the potential pitfalls of decision making shortcuts using hormone
      therapy (HT) in menopause as an example. DISCUSSION: Recent randomised controlled
      trials have changed the thinking on the risk-benefit ratio for HT. The previously
      assumed long term health benefits of HT for women during and beyond menopause
      resulted from shortcuts in decision making including 'association means
      causation' (observational data), 'experts know best' (the experience of
      gynaecologists seeing women with severe menopausal symptoms is applied to all
      women) and 'a biological theory to explain a phenomenon makes it likely to be
      true' (oestrogen has a positive effect on lipid profiles and so was assumed to be
      cardioprotective).

PMID- 15584337
TI  - Better outcomes--a case study.
AB  - It is estimated that mental health problems will affect more than 20% of the
      Australian adult population in their lifetime. The 2001 Australian Commonwealth
      budget provided dollars 120.4 million over 4 years to improve the quality of care
      provided through general practice to Australians with a mental health illness.
      The Better Outcomes in Mental Health Care (BOMHC) initiative--which forms part of
      the National Mental Health Strategy--began in 2001 and aimed to improve the
      quality of care provided through general practice to patients with a mental
      health problem. This article reviews the uptake of education and training
      initiatives of the BOMHC initiative and good uptake by general practitioners
      across Australia. Well over 3600 GPs have completed the first 'level' of training
      associated with the initiative, representing 16.5% of the GP population. Access
      by consumers to mental health trained and registered GPs also significantly
      improved, with one in four practices employing a GP registered with the BOMHC
      initiative.

PMID- 15584338
TI  - What's new in research that should change the way we detect and treat
      hypertension?

PMID- 15584339
TI  - Data monitoring (and safety) committees--what are they and why do we need them?
      Primary Care Alliance for Clinical Trials (PACT) Network.

PMID- 15584340
TI  - Sphygmomanometers--an audit in general practice.
AB  - BACKGROUND: The accuracy of sphygmomanometers used in Australian general practice
      is unknown but potentially important. METHOD: We measured the accuracy of
      sphygmomanometers in general practice in the Hunter region of New South Wales
      using a gold standard. Practices were recruited by an advertisement in the
      division newsletter. RESULTS: Sixty practices (35%) volunteered. A total of 404
      instruments were checked. Over 95% of sphygmomanometers were within 4 mmHg of
      gold standard sphygmomanometer across the clinical pressure range. Mercury
      sphygmomanometers were more accurate than aneroid (p<0.01). There was no
      significant association between accuracy and age, calibration, or visual
      inspection of the instruments. DISCUSSION: This study demonstrated a high
      accuracy rate of the sphygmomanometers checked, especially those
      sphygmomanometers that were mercury.

PMID- 15584341
TI  - The use of herbal medicines for the treatment of menopausal symptoms. A pilot
      study of women attending general practice.

PMID- 15584342
TI  - GPs' views on active nutrition management for their patients.

PMID- 15584343
TI  - Doctor-patient treatment goals in the management of osteoarthritis in general
      practice.

PMID- 15584344
TI  - [Treatment of cystic lesions in petrous apex using pneumatisation mechanism].

PMID- 15584345
TI  - [Does molecular targeted therapy change the treatment for lung cancer?].

PMID- 15584346
TI  - [Progress of artificial vessel].

PMID- 15584347
TI  - [Postoperative bleeding after tooth extractions in patients controlled with
      warfarin--a clinico-statistical study on the factors influencing postoperative
      bleeding].
AB  - There are many reports about tooth extractions of patients taking warfarin,
      however PT-INR level is used to examine the postoperative bleeding in patients.
      To investigate other factors, postoperative bleeding, age, gender, PT-INR level,
      combined use of anti-platelet drugs, conditions of extracted tooth, a number of
      tooth extractions at a treatment, methods of management for warfarin therapy,
      degree of the alveolar bone loss and size of radiolucency of apical region were
      examined in this study. To apply Mann-Whitney U-test and chi2-test, ninety-three
      patients (38 male and 55 female) who took warfarin and visited our clinic for
      tooth extractions from April 1994 to November 2002 were classified into 2 groups:
      One group showed hemostasis by the next day (77 patients), the other showed the
      continuous bleeding after the next day (16 patients). These analyses indicated
      that PT-INR level, a number of tooth extractions at a treatment, methods of
      management for warfarin therapy, and size of radiolucency of apical region
      influenced postoperative bleeding. In addition, stepwise logistic regression
      analysis was applied to all of the factors, obtained from 77 patients out of 93
      patients. This data showed that PT-INR level, a number of tooth extractions at a
      treatment and methods of management for warfarin therapy influenced postoperative
      bleeding. These results suggest that before the tooth extractions not only PT-INR
      level but methods of management for warfarin therapy and size of wound could be
      important to control the postoperative bleeding in warfarin taking patients.

PMID- 15584348
TI  - [Cell biology of retinal neuronal cells--cross-over between clinical and basic
      sciences].

PMID- 15584349
TI  - [Ocular inflammation with varicella-zoster virus and immune privilege].
AB  - Mice with experimental acute retinal necrosis (ARN) induced by herpes simplex
      virus fail to acquire virus-specific delayed hypersensitivity (DH), even though
      they produce antiviral antibodies. We investigated whether there was a similar
      correlation for patients with varicella zoster virus(VZV)-induced ARN or patients
      with anterior uveitis caused by VZV. Patients with acute, VZV-induced ARN, with
      anterior uveitis with dermatitis(herpes zoster ophthalmicus, ZO-AU), or with
      anterior uveitis without dermatitis(zoster sine herpete, ZSH-AU) were skin-tested
      with VZV to evaluate DH. All patients with VZV-induced skin disease alone(control
      group) displayed intense DH when tested with VZV antigen. In contrast, subsets of
      patients with ARN or ZO-AU displayed absent VZV-specific DH. Patients with the
      most severe ARN or ZO-AU had the lowest DH responses to VZV antigens. Serum anti
      VZV antibody titers were higher in ARN patients than in normal subjects, and anti
      viral titer correlated inversely with intensity of anti-VZV DH responses. VZV
      specific DH responses were restored in patients who recovered from ARN or from
      anterior uveitis caused by VZV. Patients with ZSH-AU also failed to display VZV
      specific DH. Absence of DH reactivity to VZV antigens appears to be a concomitant
      feature of VZV-uveitis of high intensity.

PMID- 15584350
TI  - [Molecular mechanism of pathological keratinization in severe ocular surface
      diseases].
AB  - PURPOSE: To investigate the molecular mechanism of pathological keratinization in
      severe ocular surface diseases based on the process of epidermal physiological
      keratinization and the gene expression profile of ocular surface epithelium.
      MATERIALS AND METHODS: We examined conjunctiva covering corneas which had ocular
      surface diseases in which pathological keratinization was seen. We then
      investigated the expression of epidermal keratinization-related proteins and
      clusterin, which is the most abundant gene transcript in human corneal
      epithelium. RESULTS: Semiquantitative reverse transcription-polymerase chain
      reaction(RT-PCR) and immunohistochemistry showed that transglutaminase 1,
      involucrin, filaggrin, and cytokeratin 1/10 expression was upregulated in
      keratinized conjunctiva compared to normal conjunctiva. On the other hand, the
      level of clusterin expression in the diseased ocular surfaces was significantly
      lower than normal. We also concluded that clusterin expression may depend on the
      severity of the pathological keratinization. CONCLUSION: Various keratinization
      related proteins and clusterin are most likely to be involved in the pathogenesis
      of cicatrizing ocular surface diseases.

PMID- 15584351
TI  - [Molecular genetic study of congenital stationary night blindness].
AB  - PURPOSE: Molecular genetic study was conducted on patients with fundus
      albipunctatus, incomplete and complete types of congenital stationary night
      blindness(CSNB), and Oguchi disease. RESULTS: Mutations in the RDH5 gene were
      identified in all 10 patients with typical clinical features of fundus
      albipunctatus. Mutations in the gene were also detected in patients with fundus
      albipunctatus associated with cone dystrophy, and it was supposed that mutations
      of the gene cause progressive retinal dystrophy as well as fundus albipunctatus.
      Mutations in the CACNA1F gene were identified in all 15 patients with typical
      clinical features of incomplete CSNB. We found that some cases with incomplete
      CSNB were associated with retinal degeneration or optic atrophy with progressive
      impairment of vision. We detected mutations in the NYX gene in about half of the
      cases with complete CSNB. Molecular examination was useful to determine the exact
      hereditary pattern. We examined the arrestin gene and the rhodopsin kinase gene
      in 5 unrelated patients with Oguchi disease, and found arrestin gene mutations in
      4 of them and a rhodopsin kinase gene mutation in the fifth patient. CONCLUSIONS:
      We confirmed that fundus albipunctatus, incomplete CSNB, complete CSNB, and
      Oguchi disease were associated with mutations in the RDH5, CACNA1F, NYX, arrestin
      or rhodopsin kinase genes, respectively, in Japanese patients. Molecular analysis
      made it possible to diagnose patients with atypical phenotype and to obtain novel
      information about phenotypic variation.

PMID- 15584352
TI  - [Function of glial cell network as a modulator of neural cell death during
      retinal degeneration].
AB  - PURPOSE: Recent studies have demonstrated the mechanism of neural cell death,
      neuroprotection, and regeneration. However, the functional importance of glial
      cells during retinal degeneration is not well understood. In this review, we
      summarize our recent progress regarding the function of glial cells in
      neurotrophic factor production and neural cell death during retinal degeneration.
      METHODS: We made a rat model of photoreceptor degeneration by continuous light
      exposure, and examined the distribution and expression levels of neurotrophins
      and their receptors. In addition, we carried out quantitative analysis of
      neurotrophic factor production in cultured Muller glial cells and microglia.
      RESULTS: In the light-degenerated retina, microglia invade the photoreceptor
      layer from the inner part of the retina and increase the production of nerve
      growth factor (NGF). NGF decreases the production of basic fibroblast growth,
      factor, which prevents photoreceptor cell death, in Muller glial cells through
      low-affinity neurotrophin receptor p 75. Blockade of p 75 decreased photoreceptor
      cell death during light-induced retinal degeneration. CONCLUSIONS: These results
      suggest that a gliaglia network plays a critical role in neural cell death during
      retinal degeneration. Thus, a glia-glia network as well as a glia-neuron network
      could be a possible therapeutic target for inhibition of retinal degeneration.

PMID- 15584353
TI  - [Roles of cytokines in the development of severe allergic conjunctival diseases:
      analyses using animal models].
AB  - Conjunctival papillary formation and corneal damage, which are seen in severe
      types of allergic conjunctival diseases, are mediated by eosinophils. Eosinophils
      themselves are not able to recognize a specific antigen (Ag) and thus, Ag
      specific T cells are thought to be important for eosinophilic infiltration into
      the conjunctiva. Cytokines, which are produced by Ag-specific T cells followed by
      Ag recognition, are considered to be involved in eosinophilic infiltration.
      Therefore, we investigated the involvement of cytokines, which are produced by
      immunocompetent cells and conjunctival cells, in the infiltration of inflammatory
      cells into the conjunctiva, using an animal model for allergic conjunctival
      diseases (experimental immune-mediated blepharoconjunctivitis, EC). The peak of
      expression of Th 2 cytokines such as interleukin (IL)-4 in the rat conjunctiva
      was 6 and 12 hours after Ag challenge. In contrast, expression of Th1 cytokines
      such as interferon (IFN)-gamma persisted up to 48 hours after Ag challenge. The
      kinetic change of IL-4 was concordant with eosinophilic infiltration into the
      conjunctiva and that of IFN-gamma was in accord with infiltration of macrophages.
      To investigate the roles of these cytokines, we induced conjunctivitis in
      cytokine knockout mice. The infiltration of inflammatory cells was attenuated in
      IL-4 knockout mice, whereas it was augmented in IFN-gamma knockout mice. To
      further elucidate the roles of these cytokines, we induced and analyzed EC in
      Brown Norway rats. Eosinophilic infiltration was increased in EC induced by the
      transfer of T cells, which were stimulated by IL-4. In addition, systemic
      treatment with IFN-gamma inhibited eosinophilic infiltration in EC induced by
      active immunization, but did not affect infiltration of inflammatory cells in EC
      induced by passive immunization. These results demonstrate that IL-4 and IFN
      gamma are involved in the infiltration of eosinophils and macrophages,
      respectively. In addition, IFN-gamma exerts its suppressive effects on the
      development of EC only during the induction phase of EC. Further detailed studies
      investigating the roles of cytokines in the conjunctiva will elucidate the
      developing mechanism of allergic conjunctival diseases. These studies will
      provide important clues for a therapeutic approach in targeting cytokines.

PMID- 15584354
TI  - [Ocular surface temperature of meibomia gland dysfunction patients and the
      melting point of meibomian gland secretions].
AB  - PURPOSE: Since meibomian gland dysfunction (MGD) is thought to be caused by
      raising of the melting point and degeneration of lipid secretions, the melting
      point of secretions and the temperature of the ocular surface were investigated.
      SUBJECTS AND METHODS: Twenty-three patients with MGD [mean age 69.3 +/- 7.2 (mean
      standard deviation) years) were examined. Seven subjects without MGD (mean age
      32.5 +/- 5.8 years) were also observed as controls. METHODS: Solid secretions
      obtained from MGD patients were heated and the melting point was measured. The
      weight ratio of lipids and cell components was also determined. RESULTS: Corneal
      temperature was 32.3 +/- 0.5 (mean +/- standard deviation) degrees C and eyelid
      temperature was 33.1 +/- 0.5 degrees C in the control subjects. Corneal
      temperature was 31.1 +/- 0.8 degrees C and eyelid temperature was 32.7 +/- 0.6
      degrees C in MGD patients. However, the melting point of the secretions was 34.0
      +/- 1.3 degrees C, which was higher than the temperature of the ocular surface
      and eyelid in both patients and controls. The cell components constituted about
      60% of the secretions and the lipid composition, about 40%. CONCLUSION: The cause
      of MGD is thought to be solid ification of lipids because of elevation of the
      melting point and the increase in the cell components of the secretions.

PMID- 15584355
TI  - [Incidence of endogenous uveitis at Kyushu University Hospital].
AB  - PURPOSE: We performed a clinical statistical study on recent patients with
      endogenous uveitis at the clinic of the Department of Ophthalmology, Kyushu
      University Hospital. SUBJECTS: We studied 616 patients with endogenous uveitis
      who first visited the clinic of the Department of Ophthalmology, Kyushu
      University Hospital, between January 1996 and December 2001. RESULTS AND
      CONCLUSION: The most frequent clinical entity was sarcoidosis (8.6%), followed by
      Behcet's disease (8.4%), Vogt-Koyanagi-Harada syndrome (6.5%), human T
      lymphotropic virus type I (HTLV-1) uveitis (3.9%), and toxoplasmosis (2.6%).
      Unclassified uveitis comprised 58.1% in our study. Next we classified the
      subjects into four age groups; adolescent (0-19 years old), young (20-39 years
      old), middle-aged (40-59 years old), and elderly (60-years old). We also
      classified the disease into four groups: uveitis pan, anterior, intermediate, and
      posterior uveitis, according to the site of inflammation. The most frequent
      clinical entity was Behcet's disease in the young group, and sarcoidosis in the
      elderly group. The frequency of unclassified uveitis was high in the adolescent
      and the elderly groups. As to the anatomic diagnosis of uveitis, panuveitis was
      most frequent, followed by anterior, posterior, and intermediate uveitis. Finally
      we investigated the frequency of secondary glaucoma. The frequency in all 616
      patients was 19.7%. Secondary glaucoma was more frequent in male patients and
      more frequent in the middle-aged and the elderly groups.

PMID- 15584356
TI  - [High-resolution CT in the differential diagnosis of consolidative processes (I.
      Acute processes)].
AB  - Consolidations are usually result of the replacement of the alveolar air by
      fluid, cells or tissue but these can also be seen with extensive interstitial
      processes. These diseases cannot be clearly categorized into the classic
      classification scheme of airspace and interstitial disease since there are
      features of both categories seen in the imaging and histologic findings. Because
      this definition includes wide variety of diseases with overlapping HRCT-findings
      it is difficult to distinguish among these entities with imaging criteria alone.
      However, integration of HRCT-findings and clinical findings may enable a narrower
      differential diagnosis. This review describes the most common types of lung
      diseases associated with acute appearance of consolidation and discuss the
      differential diagnosis.

PMID- 15584357
TI  - [Computed tomography of cystic lung diseases].
AB  - A cystic lesion in the lung is defined as a well-demarcated epithel-lined cavity,
      that can be mostly filled with air, water, as well as solid material content.
      This definition includes a wide variety of diseases such as bronchogenic cyst,
      abscess formation, lymphangioleiomyomatosis, Langerhans cell histiocytosis,
      emphysema, bronchiectasis, and pneumatoceles. Despite the difficulties in
      differential diagnosis, there are some diagnostic criteria for CT-scanning
      helping the radiologist to differentiate between these cystic entities. Moreover,
      clinical informations are extremely important. The most important clinical
      parameters include age, sex, clinical history and symptoms. Thus, a better
      understanding of classic CT appearance of cystic lung disease will allow more
      definitive diagnosis and could, in some cases, avoid biopsy.

PMID- 15584358
TI  - [Segmental embolization of the gastroduodenal artery in a case of a perforated
      pseudoaneurysm and gastrointestinal massive bleeding].
AB  - We present the history of a woman suffering from an extensive gastrointestinal
      bleeding due to liver cirrhosis and chronic pancreatitis. Selective angiogram of
      the celiac artery revealed a pseudoaneurysm of the gastroduodenal artery caused
      by inflammatory wall penetration. The life-threatening hemorrhage was completely
      stopped by embolization with three stainless steel coils after microcatheter
      engagement of the gastroduodenal artery. The particularity of this case is the
      restricted embolization of the aneurysm vessel segment, so the collateral
      circulation of the gastroduodenal and pancreaticoduodenal artery could be
      preserved.

PMID- 15584359
TI  - [Posterior reversible encephalopathy syndrome (PRES) in the framework of
      hypertensive encephalopathy].

PMID- 15584360
TI  - [X-ray contrast media Melitrast-300 and Melitrast-270 in cardiological
      diagnosis].
AB  - The aim of this study was the evaluation of safety and cardiologic efficacy of
      the non-ionic contrast agent Iosarcol (Melitrast), a contrast agent with low
      protein affinity in two different iodine concentrations. One hundred patients
      were prospectively randomized to receive either Melitrast-270 or Melitrast-300
      for left heart ventriculography and coronary angiography. Clinical evaluation,
      blood pressure and pulse measurement were performed and an electrocardiogram was
      recorded before and after contrast application and the diagnostic efficacy using
      a score was evaluated. In three patients side effects could be observed 2 hours
      after the application (vertigo, sickness, sweating). Melitrast in both
      concentrations led to a good contrast during ventriculography and coronary
      angiography which could not be differentiated by two experienced observers. Thus
      a lower iodine concentration and by this a lower viscosity seems to favour
      Melitrast-270 for invasive cardiologic diagnosis.

PMID- 15584361
TI  - [Results of radiation therapy in periarthritis humeroscapularis].
AB  - BACKGROUND: Radiation therapy is applied in painful degenerative shoulder
      diseases. Aim of this work was to evaluate the contribution of radiation therapy
      to symptomatic improvement in periarthritis humeroscapularis. METHODS: Ninety
      four patients with periarthritis humeroscapularis were treated in two
      institutions. Mean age was 68 years, sex distribution were 32 men and 62 women.
      In 58 cases the right side was affected, left in 36 cases. At single doses of
      0.75 Gy once a week a total dose of 6 Gy was applied (Fig. 1). The treatment
      effect was evaluated by the standardized von Pannewitz-score at the end of the
      treatment up to 6 months thereafter. RESULTS: The treatment results of all the 94
      patients were documentated at the end of therapy. Seventy-one patients were
      followed at least for further 4 months. Radiogenic side-effects were not noticed.
      The symptoms of 54 patients (57.4%) were improved or vanished, in 40 cases the
      symptoms were not significantly affected (42.6%) (Table 1). Four months after
      therapy 42 of 71 patients were improved (59.2%), 29 unchanged (40.8%) (Table 2).
      The treatment effect occured typically up to 2 months after therapy, there were
      no age-related differences. Also in recurrent radiation therapies the symptoms
      improved, in 80 percent after one preceding therapy (Table 3), however only in
      31.2 percent after multiple prior radiotherapies (Table 4). CONCLUSION: Radiation
      therapy is effective in the symptomatic treatment of periarthritis
      humeroscapularis. Treatment should be performed early after initial conservative
      treatment prior to any invasive therapy.

PMID- 15584362
TI  - The urgent need for evidence-based CAM in the world.

PMID- 15584363
TI  - Beginnings.

PMID- 15584364
TI  - Complementary and alternative medicine in Japan.

PMID- 15584365
TI  - New scientific approach for natural medicine: examples of Kampo medicine.

PMID- 15584366
TI  - The modernization of traditional Chinese medicine in Taiwan--past, present and
      future.

PMID- 15584367
TI  - Quality requirements for herbal medicinal products in Europe.

PMID- 15584368
TI  - Integrating medical knowledge: old roots and a modern science-based approach at
      the University of Milan.

PMID- 15584369
TI  - Identification of diseases that may be targets for complementary and alternative
      medicine (CAM).

PMID- 15584370
TI  - Complementary and alternative medicine during HIV infection.

PMID- 15584371
TI  - A polyherbal formulation for a wide spectrum of reproductive tract and sexually
      transmitted infections.

PMID- 15584372
TI  - Anticancer therapeutic potential of soy isoflavone, genistein.
AB  - Genistein (4'5, 7-trihydroxyisoflavone) occurs as a glycoside (genistin) in the
      plant family Leguminosae, which includes the soybean (Glycine max). A significant
      correlation between the serum/plasma level of genistein and the incidence of
      gender-based cancers in Asian, European and American populations suggests that
      genistein may reduce the risk of tumor formation. Other evidence includes the
      mechanism of action of genistein in normal and cancer cells. Genistein inhibits
      protein tyrosine kinase (PTK), which is involved in phosphorylation of tyrosyl
      residues of membrane-bound receptors leading to signal transduction, and it
      inhibits topoisomerase II, which participates in DNA replication, transcription
      and repair. By blocking the activities of PTK, topoisomerase II and matrix
      metalloprotein (MMP9) and by down-regulating the expression of about 11 genes,
      including that of vascular endothelial growth factor (VEGF), genistein can arrest
      cell growth and proliferation, cell cycle at G2/M, invasion and angiogenesis.
      Furthermore, genistein can alter the expression of gangliosides and other
      carbohydrate antigens to facilitate their immune recognition. Genistein acts
      synergistically with drugs such as tamoxifen, cisplatin, 1,3-bis 2-chloroethyl-1
      nitrosourea (BCNU), dexamethasone, daunorubicin and tiazofurin, and with
      bioflavonoid food supplements such as quercetin, green-tea catechins and black
      tea thearubigins. Genistein can augment the efficacy of radiation for breast and
      prostate carcinomas. Because it increases melanin production and tyrosinase
      activity, genistein can protect melanocytes of the skin of Caucasians from UV-B
      radiation-induced melanoma. Genistein-induced antigenic alteration has the
      potential for improving active specific immunotherapy of melanoma and carcinomas.
      When conjugated to B43 monoclonal antibody, genistein becomes a tool for passive
      immunotherapy to target B-lineage leukemias that overexpress the target antigen
      CD19. Genistein is also conjugated to recombinant EGF to target cancers
      overexpressing the EGF receptor. Although genistein has many potentially
      therapeutic actions against cancer, its biphasic bioactivity (inhibitory at high
      concentrations and activating at low concentrations) requires caution in
      determining therapeutic doses of genistein alone or in combination with
      chemotherapy, radiation therapy, and/or immunotherapies. Of the more than 4500
      genistein studies in peer-reviewed primary publications, almost one fifth pertain
      to its antitumor capabilities and more than 400 describe its mechanism of action
      in normal and malignant human and animal cells, animal models, in vitro
      experiments, or phase I/II clinical trials. Several biotechnological firms in
      Japan, Australia and in the United States (e.g., Nutrilite) manufacture genistein
      as a natural supplement under quality controlled and assured conditions.

PMID- 15584373
TI  - Chinese medicine and immunity.

PMID- 15584374
TI  - Testing efficacy of natural anxiolytic compounds.

PMID- 15584375
TI  - Alternative approaches to pain relief during labor and delivery.

PMID- 15584376
TI  - Alternative and comparative medicine in dentistry.

PMID- 15584377
TI  - Methodological concerns when designing trials for the efficacy of acupuncture for
      the treatment of pain.
AB  - The aim of all clinical research must surely be to assess an intervention or
      process or relationship between variables, ultimately in order to be able to
      improve clinical practice and healthcare for patients/consumers. As such,
      evidence gathered must have external validity (generalisability) and it must be
      relevant to clinical practice. It can be seen therefore that research into
      acupuncture for pain relief is an inherently difficult task, which requires much
      sensitivity and careful planning in order to minimise error when drawing
      conclusions. The researcher needs to adequately address problems such as sample
      size, blinding, randomisation and appropriate use of control and treatment. It is
      also most important to be able to clarify that the placebo (if used) is credible
      to the patient. The field of acupuncture has been overwhelmed with hundreds of
      sub-standard trials and much doubt still surrounds the issue of efficacy. Few
      good quality rigorous trials exist to support the use of acupuncture for pain
      relief in general. It has also been noted that the question of long-term efficacy
      has not been assessed by the many trials and this needs to be addressed prior to
      its acceptance. Further well conducted rigorous trials are therefore needed,
      utilising the lessons learnt through the substantial number of previous trials,
      in order to adequately assess the efficacy of acupuncture for painful conditions.
      Such trials must therefore: Utilise a placebo control. Be randomised and
      stratified. Ensure patient blinding. Use self completed outcome measures and
      blinded assessors. Have sufficient and well validated outcome measures. Check
      credibility of treatment. Have a well defined entry criteria which includes a
      single condition only. Have a long term follow up. Enrol sufficient subjects, the
      number to be determined by a power calculation. Provide adequate acupuncture
      treatment as would be found in clinical practice. Be group comparative so as to
      negate any carry-over effects. In this way good quality trials can be undertaken
      which will yield reliable results and therefore add meaningful data to the body
      of knowledge appertaining to the effectiveness of acupuncture.

PMID- 15584378
TI  - Treatment for atopic dermatitis by acupuncture.

PMID- 15584379
TI  - Hydrotherapy can modulate peripheral leukocytes: an approach to alternative
      medicine.

PMID- 15584380
TI  - Music therapy, wellness, and stress reduction.

PMID- 15584381
TI  - Music therapy, a future alternative intervention against diseases.

PMID- 15584382
TI  - Diet instruction for Japanese traditional food in therapy for atopic dermatitis.

PMID- 15584383
TI  - Kampo therapy for adult atopic dermatitis by dieting and herbal medications:
      evaluating the disappearance of disease phases. Dieting and herbs for atopic
      dermatitis.

PMID- 15584384
TI  - Management of nutritional and health needs of malnourished and vegetarian people
      in India.

PMID- 15584385
TI  - Cultural heritage: porifera (sponges), a taxon successfully progressing
      paleontology, biology, biochemistry, biotechnology and biomedicine.

PMID- 15584386
TI  - Earthworms: sources of antimicrobial and anticancer molecules.

PMID- 15584387
TI  - What can we learn from marine invertebrates to be used as complementary
      antibiotics?

PMID- 15584388
TI  - Nervous, endocrine, immune systems as a target for complementary and alternative
      medicine.

PMID- 15584389
TI  - Scientific thinking: its history, methods, and advantages.

PMID- 15584390
TI  - Glycome: a medical paradigm.

PMID- 15584391
TI  - [Pyrogallic method for the determination of protein in urine (literature
      survey)].

PMID- 15584392
TI  - [Fundamentals of the laboratory diagnosis in inherited hemochromatosis
      (literature survey)].

PMID- 15584393
TI  - [Non-enzymatic chain of the antioxidant system and oxidant resistance of low
      density lipoproteins in metabolic syndrome].
AB  - The oxidant resistance of low-density lipoproteins was shown in patients with
      metabolic cardiovascular syndrome to be reduced versus healthy donors. A changing
      total antiradical activity of blood serum is an important factor for such
      reduction of the antioxidant resistance in the above pathology. The level of
      tocopherol in blood serum could be the most significant chain determining the
      mentioned activity in patients with metabolic cardiovascular syndrome.

PMID- 15584394
TI  - [Significance of biochemical parameters of saliva in the diagnosis of chronic
      obstructive pulmonary disease at exacerbation].
AB  - The levels of calcium, magnesium and iron were examined on an automated
      biochemical analyzer in saliva and blood serum of 102 patients with chronic
      obstructive disease of lungs (CODL) and of 20 healthy subjects. Reliably reduced
      levels of magnesium and iron in saliva as well as low permeability of the
      hematosalivary barrier (HSB) for magnesium and its high permeability for iron
      were detected in group 2 and 3 of patients. The dynamic level of iron in saliva
      reached the normal value, whereas, a stable salivary deficiency was typical of
      magnesium. The above tests of levels of magnesium and iron in saliva and the
      determination of the distribution factor for the above cations can be used in
      evaluating a severity of bronchial obstruction and therapy efficiency in patients
      with CODL.

PMID- 15584395
TI  - [Laboratory evaluation of urology patients after retroperitoneoscopic
      procedures].

PMID- 15584396
TI  - [The intensity of lipid peroxidation and of antioxidant activity and the level of
      average-weight molecules as indicators of endogenous intoxication in generalized
      peritonitis].

PMID- 15584397
TI  - [Potentialities of the cytological diagnosis of tumors in the pancreas and
      evaluation of the differential-diagnostic significance of computer-aided image
      analysis (literature survey)].

PMID- 15584398
TI  - [Homocystine as a new factor of risk of atherosclerosis and thrombosis
      (lecture)].

PMID- 15584399
TI  - [Potentialities of cytology in preventive examinations of samples from the
      uterine cervix].
AB  - The primary detection rate of inflammatory diseases of the neck of uterus, like
      inflammations of different etiopathogenesis, bacterial vaginosis and candidosis,
      went up, 2000-2002, by 3.2%; the above rate increase in women with gynecology
      history by 8.1%. The detection rate of bacterial vaginosis grew by 22%. Total
      cytological examinations of sample from the ectocervix and endocervix do not only
      insure the detection of morphologically changed cells, they also characterize
      their bacterial composition.

PMID- 15584400
TI  - [Models of inter-group difference of the homeostasis system in patients with
      artificial heart valves and the set of laboratory parameters].
AB  - Patients with artificial heart valves (AHV) belong to a unique multi-component
      model of the homeostasis system presenting an interaction of activated
      coagulation processes and pharmacological effects, on the one hand, and genetic
      peculiarities functioning homeostatic mechanisms, on the other hand. The
      described method was evaluated on the basis of multi-factor mathematic analysis
      by information-metry. The data obtained provided for isolating the most
      information-dense laboratory indices and some genetic polymorphisms describing
      the shaping of continuous intravascular coagulation of stage III in AHV patients.
      The clinicians and laboratory experts are offered a practical instrument for the
      diagnosis (prognostication) of the above condition. It was proven as necessary to
      examine (by the morphofunctional method) the intravascular activation of
      platelets and to determine the D-dimer in the remote period after prosthesis of
      heart valves.

PMID- 15584401
TI  - [Choosing of disaggregants for the treatment of patients with instable angina
      without lifting the ST segment].
AB  - The cases study dealt with choosing an individual antiaggregant therapy for
      patients with instable angina (IA) without lifting the ST segment. Seventy-eight
      patients with IA, who were treated, apart from routine therapy, by different
      disaggregants, were examined. The aggregation of platelets was tested on the
      laser LA 230 "Biola" analyzer, Russia. Aspirin effectively suppressed the
      adrenalin-induced aggregation of platelets in 20 of 26 patients; cardiomagnil
      effectively suppressed it in all 17 patients; and plavix reliably reduced the ADP
      induced aggregation of platelets. Both types of platelets aggregation were
      reliably reduced in combined therapy (plavix plus cardiomagnil). Thus, the
      combined therapy by drugs with different action mechanisms was proven to most
      effective in patients with IA.

PMID- 15584402
TI  - [Selective broth for the accumulation of enteropathological Yersinia in the
      course of routine bacteriological examination].

PMID- 15584403
TI  - [The economic substantiation of costs for intralaboratory quality monitoring].

PMID- 15584404
TI  - [A practical experience of using the technological maps in increasing the
      efficiency of laboratory findings].

PMID- 15584405
TI  - Molecular characterization of birnaviruses isolated from wild marine fishes at
      the Flemish Cap (Newfoundland).
AB  - Several isolates of aquatic birnaviruses were recovered from different species of
      wild fish caught in the Flemish Cap, a Newfoundland fishery close to the Atlantic
      coast of Canada. The nucleotide sequence of a region of the NS gene was identical
      among the isolates and was most similar to the Dry Mills and West Buxton
      reference strains of infectious pancreatic necrosis virus (IPNV). Phylogenetic
      analysis of the sequence of a region of the VP2 gene demonstrated that the
      isolates were most closely aligned with the American strains of IPNV serotype A1.
      Electron microscopy of virus structures clarified and concentrated from cultures
      of infected chinook salmon embryo (CHSE-214) cells revealed a majority of typical
      IPNV-like icosahedral particles, as well as a low proportion of type I tubules
      having a diameter of approximately 55 nm and a variable length of up to 2 microm.
      The tubules could be propagated in cell cultures, but always in the presence of
      low proportions of icosahedral particles. Cloning of selected isolates by serial
      dilution yielded preparations with a high proportion of the tubular structures
      with a density in CsCl gradients of approximately 1.30 g cm(-3). Polyacrylamide
      gel electrophoresis revealed the material in the band was composed of the IPNV
      pVP2 and VP2 proteins.

PMID- 15584406
TI  - Genetic population structure of marine viral haemorrhagic septicaemia virus
      (VHSV).
AB  - The nucleotide sequences of a specific region of the nucleoprotein gene were
      compared in order to investigate the genetic population structure of marine viral
      haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates
      of diverse geographic and host origin renders this the most comprehensive
      molecular epidemiological study of marine VHSV conducted to date. Phylogenetic
      analysis of nucleoprotein gene sequences confirmed the existence of the 4 major
      genotypes previously identified based on N- and subsequent G-gene based analyses.
      The range of Genotype I included subgroups of isolates associated with rainbow
      trout aquaculture (Genotype Ia) and those from the Baltic marine environment
      (Genotype Ib) to emphasise the relatively close genetic relationship between
      these isolates. The existence of an additional genotype circulating within the
      Baltic Sea (Genotype II) was also confirmed. Genotype III included marine
      isolates from around the British Isles in addition to those associated with
      turbot mariculture, highlighting a continued risk to the development of this
      industry. Genotype IV consisted of isolates from the marine environment in North
      America. Taken together, these findings suggest a marine origin of VHSV in
      rainbow trout aquaculture. The implications of these findings with respect to the
      future control of VHSV are discussed. The capacity for molecular phylogenetic
      analysis to resolve complex epidemiological problems is also demonstrated and its
      likely future importance to disease management issues highlighted.

PMID- 15584407
TI  - Molecular characterization of Sp serotype strains of infectious pancreatic
      necrosis virus exhibiting differences in virulence.
AB  - Infectious pancreatic necrosis virus (IPNV), a prototype virus of the family
      Birnaviridae, exhibits a high degree of antigenic variability, pathogenicity and
      virulence in salmonid species. The Genomic Segment A encodes all the structural
      (VP2 and VP3) and nonstructural (NS) proteins, whereas Segment B encodes the
      viral RNA-dependent RNA polymerase (VP1). We tested 3 different IPNV isolates
      (Sp103, Sp116 and Sp122) isolated during field outbreaks in Norway for their
      ability to cause mortality in fry and post-smolt of Atlantic salmon Salmo salar
      L. The cumulative mortality following experimental challenge in fry was 29% for
      Sp122 followed by 19% for Sp116 and 15% for Sp103. In post-smolt, the
      corresponding mortality rates were 79, 46 and 16%, respectively. Comparisons of
      the deduced amino acid sequences of Segments A and B of all 3 Sp strains revealed
      substitutions of residues in 13 positions, of which 6 are in VP2, 2 in VP3, and 5
      in VP1. Our results suggest that these residues, especially those in the outer
      capsid VP2, may be involved in the virulence of IPNV. Genome Segment A of the Sp
      serotype is 3097 nucleotides long and contains a major open reading frame (ORF)
      encoding a polyprotein of 972 amino acids, which initiates at the second in-frame
      start codon at Position 119. This was ascertained by making mutants of Segment A
      clone using site-directed mutagenesis, followed by in vitro transcription-coupled
      translation reaction and immunoprecipitation analyses. In addition, Segment A
      also encodes a 15 kDa arginine-rich non-structural protein from a small ORF,
      preceding and partially overlapping the polyprotein ORF, which is truncated to 12
      kDa in the virulent Sp122 strain. Moreover, Segment A could encode a novel,
      putative 25 kDa protein from another ORF between VP2 and VP4 coding regions,
      which is only detected in the Sp serotype. Segment B is 2777 nucleotides long and
      encodes in a single large ORF (a polypeptide of 844 amino acid residues), VP1.

PMID- 15584408
TI  - Characterization of the 23S and 5S rRNA genes and 23S-5S intergenic spacer region
      (ITS-2) of Photobacterium damselae.
AB  - The 23S ribosomal RNA (rRNA) gene has been sequenced in strains of the fish
      pathogens Photobacterium damselae subsp. damselae (ATCC 33539) and subsp.
      piscicida (ATCC 29690), showing that 3 nucleotide positions are clearly different
      between subspecies. In addition, the 5S rRNA gene plus the intergenic spacer
      region between the 23S and 5S rRNA genes (ITS-2) were amplified, cloned and
      sequenced for the 2 reference strains as well as the field isolates RG91 (subsp.
      damselae) and DI21 (subsp. piscicida). A 100% similarity was found for the
      consensus 5S rRNA gene sequence in the 2 subspecies, although some
      microheterogeneity was detected as inter-cistronic variability within the same
      chromosome. Sequence analysis of the spacer region between the 23S and 5S rRNA
      genes revealed 2 conserved and 3 variable nucleotide sequence blocks, and 4
      different modular organizations were found. The ITS-2 spacer region exhibited
      both inter-subspecies and intercistronic polymorphism, with a mosaic-like
      structure. The EMBL accession numbers for the 23S, 5S and ITS-2 sequences are: P.
      damselae subsp. piscicida 5S gene (AJ274379), P. damselae subsp. damselae 23S
      gene (Y18520), subsp. piscicida 23S gene (Y17901), P. damselae subsp. piscicida
      ITS-2 (AJ250695, AJ250696), P. damselae subsp. damselae ITS-2 (AJ250697,
      AJ250698).

PMID- 15584409
TI  - Isolation and characterization of mycobacteria from striped bass Morone saxatilis
      from the Chesapeake Bay.
AB  - Mycobacteriosis in striped bass Morone saxatilis of Chesapeake Bay, USA, was
      first diagnosed in 1997 based on the presence of granulomatous inflammation and
      acid-fast bacteria in skin and spleen. To confirm histopathology, bacteriological
      detection and identification of mycobacteria were begun using splenic tissue from
      fish with and without skin ulcerations. On the basis of initial studies using a
      variety of selective and nonselective media, decontamination, homogenization and
      incubation conditions, a simple and quantitative recovery method using aseptic
      necropsy of splenic tissue was developed. Optimal recovery was obtained by spread
      plating homogenates on Middlebrook 7H10 agar with incubation for 3 mo at 23
      degrees C. Mycobacteria were recovered from 76% (n = 149/196) of fish examined.
      Mycobacterial densities exceeded 10(4) colony forming units x g tissue(-1) in 38%
      of samples (n = 63/168) that were examined using a quantitative approach. The
      most frequently recovered mycobacterium, present in 57% (n = 109/192) of
      characterized samples, was the recently named new species Mycobacterium shottsii.
      Polyinfections of M. shottsii and other mycobacteria were observed in 25% of
      samples (n = 47/192) with densities of M. shottsii usually 1 or more orders of
      magnitude higher than co-isolate(s). Other mycobacteria recovered included
      isolates that, based on phenotypic traits, resembled M. interjectum, M. marinum,
      M. scrofulaceum, M. szulgai and M. triplex. M. marinum, commonly associated with
      fish mycobacteriosis and human disease, was recovered infrequently (3%, n =
      6/192). The presence of multiple mycobacterial types occurring at high densities
      suggests that a variety of mycobacteria could be causative agents of
      mycobacteriosis in striped bass from the Chesapeake Bay. Striped bass is the
      major recreational fish species in the Chesapeake Bay, and the significance of
      the current epizootic to human health and the potential adverse effects on fish
      stocks are not known.

PMID- 15584410
TI  - Experimental infection of coho salmon Oncorhynchus kisutch by exposure of skin,
      gills and intestine with Piscirickettsia salmonis.
AB  - Piscirickettsiosis pathogenesis was examined using some tissues as entry portals
      of Piscirickettsia salmonis in coho salmon. Juvenile fish, weighing approximately
      8.4 g, were used in this trial. Inocula were prepared using the strain SLGO-95 of
      P. salmonis. The micro-organism was cultured in the CHSE-214 cell line as
      described by Fryer et al. (1990) and doses containing 10(4.7) and 10(3.7) TCID50
      were prepared. Each dose was used to infect the fish via skin, gills and
      intestine. Skin and gills were exposed by calibrated drops, and the intestine by
      an intubation through the anal opening. Some fish were injected intraperitoneally
      with the same P. salmonis doses, as positive virulence controls. Sham-inoculated
      fish for each of the tested routes were also included as negative controls.
      Piscirickettsiosis was experimentally reproduced with all the inoculation
      methods. Cumulative mortalities and survival analyses showed that the most
      effective entry portal was skin followed by intestinal intubation and finally by
      gill infection.

PMID- 15584411
TI  - Experimental infections of Atlantic salmon Salmo salar with Spironucleus
      barkhanus.
AB  - Atlantic salmon Salmo salar L. (Salmonidae) were experimentally infected with
      Spironucleus barkhanus (Diplomonadida: Hexamitidae). Parasites were found in the
      blood 1 to 8 wk after infection, after which they disappeared from the blood and
      were found mainly in the internal organs (e.g. spleen and liver), eye socket or
      muscles. Mortality (38 out of 40 infected fish) occurred when fish had lesions in
      internal organs and/or on the body surface. Uninfected fish cohabiting with
      infected fish became infected after 4 wk, indicating direct transmission. There
      was no difference in susceptibility to spironucleosis between 3 different
      families of Atlantic salmon. All families developed the disease with a similar
      pattern of parasitaemia in the blood, similar clinical signs and gross pathology,
      and with very high mortality (29 out of 30). Clinical signs of systemic
      spironucleosis may include anemia, skin blisters, muscle ulcerations or
      unilateral exophthalmia. Gross pathologies include hemorrhaging of internal
      organs, splenomegaly or deformed (globulated) spleen, or granulomatous lesions in
      the spleen and liver.

PMID- 15584412
TI  - Strain variation and geographic endemism in Streptococcus iniae.
AB  - Twenty-six Israeli isolates of Streptococcus iniae from both marine and
      fresh/brackish water sources were compared with each other and with 9 foreign
      isolates. All the isolates were tentatively identified according to their
      biochemical profile. Direct sequencing of approximately 600 bp PCR products of
      the 16S rDNA confirmed their identification as S. iniae at the molecular level
      and revealed a new (one-nucleotide) variant among Israeli isolates, in addition
      to 2 variants that had been previously reported. Strain variation was further
      examined by subjecting the isolates to randomly amplified polymorphic DNA (RAPD)
      and amplified fragment length polymorphism (AFLP) analyses. The RAPD method
      allowed separation of the isolates into only 2 groups, one including 5 Israeli
      fresh/brackish water isolates and one including all the other isolates. The AFLP
      method grouped the Israeli marine isolates into one homogeneous cluster, although
      they had been obtained in different years (1995 to 2001) from different species
      of fish, and from wild (Red Sea) as well as cultured (both Mediterranean and Red
      Sea) sources. The Israeli fresh/brackish water isolates and foreign isolates
      separated into distinct entities that clustered at generally high degrees of
      similarity. The distance between the clusters of the Israeli marine and
      fresh/brackish water isolates indicates that the S. iniae streptococcosis that
      has been afflicting the aquaculture industries in the 2 environments in recent
      years was caused by distinct strains. AFLP showed superior discriminative
      properties over RAPD in detecting intraspecific variation and proved to be an
      important tool for the characterization of S. iniae. A correlation between strain
      variation and geographic endemism was established.

PMID- 15584413
TI  - Transmission of Batrachochytrium dendrobatidis within and between amphibian life
      stages.
AB  - Chytridiomycosis is an emerging infectious disease caused by the chytrid fungus
      Batrachochytrium dendrobatidis, which has been implicated in amphibian declines
      worldwide. The mountain yellow-legged frog Rana muscosa is a declining amphibian
      species that can be infected by B. dendrobatidis; however, transmission between
      conspecifics has not been documented. Here, we present experimental evidence that
      R. muscosa tadpoles can be infected by fungal zoospores and that they can
      transmit infection to each other and to postmetamorphic animals. We compared
      several techniques for detecting B. dendrobatidis transmission and found that
      histology with serial sectioning was able to detect infection before cytology or
      visual inspections. We also show that R. muscosa tadpoles appear healthy with B.
      dendrobatidis infection, while postmetamorphic animals experience mortality. In
      addition, we provide guidelines for visually detecting B. dendrobatidis in R.
      muscosa tadpoles, which may be useful in other affected species. Field surveys of
      infected and uninfected populations verify this identification technique.

PMID- 15584414
TI  - Co-localisation of Batrachochytrium dendrobatidis and keratin for enhanced
      diagnosis of chytridiomycosis in frogs.
AB  - Chytridiomycosis is a disease of post-metamorphic frogs caused by the fungus
      Batrachochytrium dendrobatidis and is associated with large declines in frog
      populations on a global scale. B. dendrobatidis is found only in the keratinised
      tissues, which include the mouthparts of healthy tadpoles. The epidermis of
      infected post-metamorphic frogs is thickened (hyperkeratosis) and the superficial
      layer can sometimes slough. Diagnosis is most commonly performed on stained
      sections of toe clips or ventral skin. Accurate interpretation can be difficult
      and requires a high level of expertise, particularly in infected animals
      exhibiting hyperkeratosis with sloughing. Misdiagnosis can occur when
      zoosporangia of B. dendrobatidis are shed with the superficial keratin layers. We
      have developed a staining protocol based on previously described methods to
      detect both B. dendrobatidis and keratin, to improve the sensitivity and
      specificity of diagnosis of chytridiomycosis by inexperienced diagnosticians.

PMID- 15584415
TI  - Molecular detection of a haplosporidian parasite in carpet shell clam Ruditapes
      decussatus from Spain.
AB  - A protozoan parasite identified by histology as a haplosporidian was detected in
      carpet shell clam Ruditapes decussatus from Spain during routine samplings.
      Analysis based on the sequence of the small subunit ribosomal RNA gene revealed
      that this organism was related to the haplosporidian group, mainly to
      Urosporidium. A specific probe was used for in situ hybridization studies to show
      the specificity of the amplified sequence.

PMID- 15584416
TI  - Description of a new actinosporean type from South African freshwaters.
AB  - Actinospore infection of oligochaetes collected from the mud of 2 freshwater
      biotopes in South Africa was studied. Using the 'cell-well plate method', a new
      aurantiactinomyxon type was found in 1.1% of the examined Branchiura sowerbyi
      oligochaete specimens from the Rietvlei River, north of Johannesburg, Gauteng,
      South Africa. In 1.5% of B. sowerbyi collected in a pond (Padda Dam), near the
      Rand Afrikaans University, Johannesburg, the same aurantiactinomyxon type was
      found. Infected oligochaetes were found only after collection and no
      actinosporean release was recorded in Branchiura specimens kept alive for several
      weeks. Actinospore infection showed a high intensity in oligochaetes in both
      positive cases. Until now, no actinosporean stages of myxosporeans have been
      described from South Africa. The aurantiactinospore type presented in this
      communication differs from the known types already described in the literature.

PMID- 15584417
TI  - Infection dynamics of Marteilia refringens in flat oyster Ostrea edulis and
      copepod Paracartia grani in a claire pond of Marennes-Oleron Bay.
AB  - The protozoan parasite Marteilia refringens has been partly responsible for the
      severe decrease in the production of the European flat oyster Ostrea edulis
      Linnaeus in France since the 1970s. The calanoid copepod Paracartia grani Sars
      was recently found to be a host for M. refringens in French shallow-water oyster
      ponds ('claires'). This study reconsidered M. refringens transmission dynamics in
      the light of this finding, taking into account not only oyster infection dynamics
      and environmental factors but also data concerning the copepod host. P. grani
      population dynamics in the claire under study revealed that this species is the
      dominant planktonic copepod in this confined ecosystem. During winter, M.
      refringens overwintered in O. edulis, with P. grani existing only as resting eggs
      in the sediment. The increase in temperature in spring controlled and
      synchronized both the release of M. refringens sporangia in the oyster feces, and
      the hatching of the benthic resting eggs of the copepod. Infection of oysters by
      M. refringens was limited to June, July and August, coinciding with (1) the
      highest temperature recorded in the claire, and (2) the highest abundance of P.
      grani. PCR detection of M. refringens in P. grani during the summer period was
      linked to the release of parasite sporangia by the oyster. Our results are
      supported by previous results on the effective transmission of this parasite from
      the oyster to the copepod.

PMID- 15584418
TI  - Haemolymph [Na+] and [Cl-] loss in Gammarus fossarum exposed in situ to a wide
      range of acidic streams.
AB  - The acid-sensitive amphipod Gammarus fossarum was exposed in situ for 24, 96 and
      168 h to 18 streams (9 draining from granite and 9 draining from sandstone
      bedrock), selected in order to provide a wide range of acidification. After 24 h,
      exposure to slightly acidic (6.00 < or = pH < or = 5.50) and strongly acidic
      water (pH < 5.50) led to a severe and significant depletion in haemolymph [Na+]
      and [Cl-] compared to organisms exposed in circumneutral water. Highly
      significant linear correlations between stream mean pH value and haemolymph [Na+]
      and [Cl-] were observed for each exposure time on each bedrock. Organisms exposed
      to slightly acid streams draining granite bedrock (pH = 5.71, pH = 5.81) showed a
      physiological adaptation after 96 h of exposure, while animals in acidic
      sandstone streams did not. Results of this study indicate that haemolymph [Na+]
      and [Cl-] in G. fossarum could be an effective ecophysiological marker for
      monitoring freshwater ecosystem acidification.

PMID- 15584419
TI  - Antimicrobial peptides discovered in the black tiger shrimp Penaeus monodon using
      the EST approach.
AB  - Two cDNA libraries were prepared from hemocytes of normal and Vibrio harveyi
      challenged black tiger shrimp Penaeus monodon. A total of 1062 expressed sequence
      tag (EST) clones were sequenced unidirectionally. ESTs representing the
      antimicrobial peptide (AMP) homologues, antilipopolysaccharide factors (ALF),
      penaeidins and crustins were discovered. They predominated among immune-related
      genes, representing 29.2% and 64.0% of the normal and challenged libraries,
      respectively. Several types of each AMP homologue were found. Sequence alignments
      of ALF in P. monodon (ALFPm 1 to 5) implied possible alternative splicing of
      different exons at both NH2 and COOH-termini. Only one major type of penaeidin
      (penPm3) was found in P. monodon. In addition, crustin homologues (crusPms1 to 4)
      and a newly identified glycine-rich antibacterial peptide (GAMPPm1) were also
      isolated and characterized. Using RT-PCR analysis, expression of ALF, penaeidin
      and crustin transcripts was detected in various tissues but the main expression
      site was in hemocytes. Expression of these antimicrobial peptides in P. monodon
      subjected to V. harveyi challenge revealed a significant increase in expression
      of ALFPms (p < 0.05) but a decrease in expression of crustins and penaeidins.

PMID- 15584420
TI  - Frequent and unexplained gonadal abnormalities in whitefish (central alpine
      Coregonus sp.) from an alpine oligotrophic lake in Switzerland.
AB  - The occurrence of a large number of whitefish with morphologically altered gonads
      in Lake Thun (Switzerland) has been reported by commercial fishermen since the
      year 2000. Macroscopic and microscopic examination of gonads revealed that 35%
      (281 out of 808) of whitefish from Lake Thun were affected. Frequency of gonadal
      abnormalities varied significantly with sex, age and ecotype of whitefish.
      Apparent females (26% [106/408]) showed significantly less gonadal alterations
      than apparent males (40% [151/225]). Fish with deformed gonads were observed in
      all age classes from 1 to 6 yr, but were most frequent in the year classes 3+ to
      5+. The gonadal alterations showed different frequencies among the 3 ecotypes of
      whitefish living in the lake: 1 ecotype was less affected (26%) than the other 2
      forms (41% and 32%, respectively). The gonadal alterations included
      adhesions/fusions to the peritoneal wall and the lateral trunk musculature
      (overall: 5%; in females: 5%; in males: 5%), asymmetry (4%; 6%; 4%), atrophy (4%;
      6%; 1%), compartmentations (11%; 4%; 18%), constrictions (3%; 1%; 7%) and
      hermaphroditism (1.1% of sampled fish, and 10 additional specimens collected by
      fishermen during the filleting process). In some cases, more than one alteration
      was observed in the same fish. Hermaphroditism manifested as 3 different types:
      (1) the lobular type, in which a consecutive sequence of testicular and ovarian
      lobes are found on the same gonad strand; (2) discrete gonads within one fish,
      with one gonad strand being ovarian tissue and the other being testicular tissue;
      and (3) the mosaic type, in which oocytes lie in tissue with normal testicular
      morphology, or spermatids or sperm are present in ovarian tissue. Several
      features of the gonadal alterations described in this study of whitefish from
      Lake Thun have also been reported for whitefish from other areas. However, the
      Lake Thun situation appears to be unique because of the high prevalence of fish
      affected and the broad variation of abnormal features. The causes of the frequent
      appearance of these gonadal alterations in whitefish from Lake Thun remain
      unclear.

PMID- 15584421
TI  - Lack of evidence of infectious salmon anemia virus in pollock Pollachius virens
      cohabitating with infected farmed Atlantic salmon Salmo salar.
AB  - The infectious salmon anemia (ISA) virus causes lethargy, anemia, hemorrhage of
      the internal organs, and death in farmed Atlantic salmon Salmo salar. It has been
      a cause of disease in Norwegian farmed Atlantic salmon since 1984 and has since
      been identified in Canada, Scotland, the United States, and the Faroe Islands.
      Wild fish have been proposed as a viral reservoir because they are capable of
      close contact with farmed salmon. Laboratory studies have shown that brown trout
      and sea trout Salmo trutta, rainbow trout Oncorhynchus mykiss, and herring Clupea
      harengus tested positive for the virus weeks after intra-peritoneal injection of
      the ISA virus. Pollock Pollachius virens are commonly found in and around salmon
      cages, and their close association with the salmon makes them an important
      potential viral reservoir to consider. The objective of this study was to
      determine the presence or prevalence of ISA virus in pollock cohabitating with
      ISA-infected farmed Atlantic salmon. Kidney tissue from 93 pollock that were
      living with ISA-infected salmon in sea cages were tested with reverse
      transcription-polymerase chain reaction (RT-PCR) test. Results yielded the
      expected 193 bp product for positive controls, while no product was observed in
      any of the pollock samples, resulting in an ISA viral prevalence of 0%. This
      study strengthens the evidence that pollock are unlikely to be an ISA virus
      reservoir for farmed Atlantic salmon.

PMID- 15584422
TI  - Rediscovery of the Australian strain of infectious hypodermal and haematopoietic
      necrosis virus.
AB  - In this study we rediscovered and verified the presence of an infectious
      hypodermal and haematopoietic necrosis virus (IHHNV) strain amongst cultured
      penaeid prawns Penaeus monodon from 1993 in Australia on the basis of a PCR
      analysis with IHHNV specific primers and sequencing of the resulting amplicons. A
      total of 7 previously published diagnostic primers specific to IHHNV were tested
      against Australian penaeid prawns and only 1 elicited a positive IHHNV PCR result
      with 16 out of 20 Australian P. monodon samples examined. In comparison, all 7
      primers produced IHHNV-positive amplicons from the New Caledonian control
      samples. Analysis and comparison of the 392 bp fragment derived from the
      Australian IHHNV strain (AY590120) with other geographical isolates revealed that
      the Madagascar isolate shared the highest nucleotide similarity (96.2%) and the
      Hawaiian and New Caledonian strain the highest nucleotide divergence (90.1 and
      90.3% respectively). The high nucleotide variation observed between the
      Australian and Hawaiian strains provides an explanation for the lack of IHHNV
      detection amongst Australian prawns with published IHHNV PCRs and commercially
      available gene probes as they are primarily designed on the basis of the Hawaiian
      strain (AF218266). Results indicated that IHHNV has been present in Australia for
      a long (geological and contemporary) time and that the virus is endemic in
      penaeid prawns in the Australian environment.

PMID- 15584423
TI  - Conservation of the DNA sequences encoding the major structural viral proteins of
      WSSV.
AB  - A cDNA library was constructed from white spot syndrome virus (WSSV)-infected
      penaeid shrimp tissue. cDNA clones with WSSV inserts were isolated and sequenced.
      By comparison with DNA sequences in GenBank, cDNA clones containing sequence
      identical to those of the WSSV envelope protein VP28 and nucleoprotein VP15 were
      identified. Poly(A) sites in the mRNAs of VP28 and VP15 were identified. Genes
      encoding the major viral structural proteins VP28, VP26, VP24, VP19 and VP15 of 5
      WSSV isolates collected from different shrimp species and/or geographical areas
      were sequenced and compared with those of 4 other WSSV isolate sequences in
      GenBank. For each of the viral structural protein genes compared, the nucleotide
      sequences were 100 to 99% identical among the 9 isolates. Gene probes or PCR
      primers based on the gene sequences of the WSSV structural proteins can be used
      for diagnoses and/or detection of WSSV infection.

PMID- 15584424
TI  - Ultrastructural identification of a herpes-like virus infection in common carp
      Cyprinus carpio in Korea.
AB  - We report on a herpes-like virus, which was found to be associated with mass
      mortality of common carp Cyprinus carpio for the first time in Korea in 1998. The
      external signs of infection in moribund fish were darkened coloration and severe
      branchial necrosis in the gill. Transmission electron microscopy revealed the
      presence of herpes-like viruses in spleen tissue. Infected spleen cells showed
      hypertrophied nuclei and degeneration. Numerous nucleocapsids of about 82 nm in
      diameter were found within the nucleus and cytoplasm of infected cells, and
      extracellular enveloped particles were also observed. We conclude that this virus
      was a likely significant cause of the high mortality of common carp in Korea in
      1998.

PMID- 15584425
TI  - Vibrio alginolyticus infection in the white shrimp Litopenaeus vannamei confirmed
      by polymerase chain reaction and 16S rDNA sequencing.
AB  - A gram-negative, rod-shaped bacterium identified as Vibrio alginolyticus was
      isolated from diseased Litopenaeus vannamei (also called Penaeus vannamei) in
      Taiwanese culture ponds. The diseased shrimp displayed poor growth, anorexia,
      inactivity, reddish pleural borders of antennae, uropods and telson, opaque and
      whitish musculature, and mortality. In histological preparations, melanized
      hemocytic granulomas were observed in the connective tissue around hemal sinuses
      together with hemocytic aggregation in necrotic musculature. Six isolates of
      Vibrio were collected from diseased shrimp at 3 farms, and these were evaluated
      for characteristics including morphology, physiology, biochemistry and
      sensitivity to antibiotics. The results indicated that the isolates belonged to a
      single species that grew in 1 to 8% NaCl, at 10 to 40 degrees C and on TCBS
      (thiosulfatecitrate-bile sucrose) agar, and that gave positive catalase, O/F
      (Oxidation/Fermentation), lysine decarboxylase, gelatinase and cytochrome-oxidase
      tests. Identification of CH003 (1 of 6 isolates) was confirmed by PCR assay for
      V. alginolyticus (expected amplicon 1486 bp). The 16S rDNA sequence (GenBank
      accession number AY373027) gave 99.9% sequence identity to V. alginolyticus
      (GenBank accession number X74690). The calculated 96 h LD50 dose of the isolated
      strain was 3.0 x 10(5) colony forming units (CFU) shrimp(-1) (6.6 x 10(4) CFU g(
      1)).

PMID- 15584426
TI  - Detection and quantification of Spironucleus barkhanus in experimentally infected
      Atlantic salmon Salmo salar.
AB  - The course of Spironucleus barkhanus (Diplomonadida: Hexamitidae) infection in
      Atlantic salmon Salmo salar L. (Salmonidae) has 2 distinct phases, a blood phase
      and a tissue phase. To detect and quantify an infection, 3 parasitological
      techniques, namely Wet Mount Examination (WME), Hematocrit Centrifuge Technique
      (HCT) and the Hemocytometer (HCM) were used. In addition, 1 immunological
      technique, enzyme-linked immunosorbent assay (ELISA), was developed to detect
      specific antibodies against S. barkhanus. This technique would be particularly
      useful for epidemiological studies where large numbers of fish had to be
      examined. It would also be a good technique to detect infection during the tissue
      phase of the disease when there were no or a low number of parasites in the
      blood.

PMID- 15584427
TI  - Intracellular invasion and persistence: survival strategies of Streptococcus suis
      and Mycobacterium avium ssp. paratuberculosis.
AB  - Streptococcus (S.) suis and Mycobacterium avium ssp. paratuberculosis (MAP)
      differ substantially in their host specificity and tissue tropism. S. suis is a
      facultative pathogen in swine, which mainly colonises the upper respiratory tract
      and can cause meningitis, septicemia, arthritis and pneumonia. In contrast, MAP
      is an obligatory pathogen causing paratuberculosis in ruminants, and shows high
      tropism for the intestinal tract. Both pathogens are able to invade and persist
      in host cells. In S. suis, the significance of invasion for pathogenesis is a
      matter of controversial discussions. In vitro it has been shown that S. suis is
      internalized by epithelial cells and survives intracellularly for at least 24 h.
      However, at present there is no evidence that S. suis invades epithelial cells
      also in vivo. In MAP, on the other hand, persistence in macrophages is generally
      considered a crucial step in pathogenesis, but it remains to be elucidated, how
      it contributes to pathophysiology of the disease. The two pathogens exemplify how
      intracellular invasion and persistence might play different roles in
      pathogenesis. In S. suis, intracellular life may represent only a transient
      retreat phase, whereas in MAP it is the predominant in vivo niche of the
      pathogen.

PMID- 15584428
TI  - [Bacterial pathogen associated molecular pattern and superantigens indirectly
      induce the accelerated death of bovine neutrophilic granulocytes].
AB  - Pathogen associated molecular patterns (PAMPs) and bacterial superantigens have
      many effects on mononuclear cells (MNC) and macrophages. Influences on
      neutrophilic granulocytes (PMN), especially by non methylated CpG motifs, gained
      less attention. Here we investigated whether PAMPs and the superantigen SEA have
      a direct or indirect influence on the survival rate of bovine PMN. Different CpG
      motifs, a reverse GpC motif, Lipopolysaccharide (LPS) and SEA did not result in a
      loss of viability of pure PMN. In the presence of MNC or in vitro generated
      macrophages (MdM), however, they induced an accelerated dying of PMN. The
      simultaneous stimulation of MNC/MdM with combinations of CpG motifs and LPS or
      SEA resulted in an additive or over additive effect: compared to control set ups,
      only 28-36% of the PMN remained viable in SEA/CpG stimulated MNC/PMN cocultures.
      Comparing autologous with allogeneic MNC/PMN or MdM/PMN cocultures, it showed up
      that not only the stimulated MNC or MdM population but also the individual
      reaction state of the PMN have an influence on the degree of PMN dying. Taken
      together, CpG motifs and other PAMPs as well as superantigens act in concert to
      reduce indirectly the viability of neutrophilic granulocytes and hence the
      functional capacity of an important effector cell population.

PMID- 15584429
TI  - [Molecular basis of Mycoplasma agalactiae pathogenicity].
AB  - Compared to other bacterial pathogens, the current knowledge of the molecular
      basis of pathogenicity of mycoplasmas is limited, and their strategies of
      infection at the molecular and cellular level remain to be elucidated. Several
      studies in the past years have shown that pathogenic mycoplasmas are equipped
      with sophisticated genetic systems, which allow these agents to spontaneously
      change their surface antigenic make-up. It is implicated that these variable
      surface components provide the wall-less mycoplasmas with a means to avoid the
      host immune response and promote host colonization. In Mycoplasma (M.)
      agalactiae, the agent of "contagious agalactia" in sheep and goats, a
      pathogenicity island-like locus has recently been identified that contains six
      distinct but related genes which encode the major immunodominant membrane
      proteins, the so-called Vpmas. It was shown that these surface-associated
      proteins vary in expression at an unusual high frequency due to site-specific DNA
      rearrangements. The previous lack of tools to genetically manipulate M.
      agalactiae has hampered more refined studies to assess the exact function of
      Vpmas in M. agalactiae infection and disease. The recent successful introduction
      of foreign DNA into the M. agalactiae genome therefore represents an important
      breakthrough which sets up the basis for a variety of follow-up studies assessing
      the role of Vpmas in molecular pathogenesis.

PMID- 15584430
TI  - [The prevalence of antimicrobial susceptibility of veterinary pathogens isolated
      from cattle and pigs: national antibiotic resistance monitoring 2002/2003 of the
      BVL].
AB  - The national antimicrobial resistance monitoring determines the current
      quantitative resistance level of life-stock pathogens, in order to permit the
      evaluation and surveillance of the distribution of resistances on a valid basis.
      During the examination period from June 2002 to July 2003, a total of 1849
      pathogens was collected, following a representative German-wide pattern in
      collaboration with 29 laboratories. The selection of examined bacterial strains
      included different specimen causing respiratory diseases in fattening pigs
      (Pasteurella multocida, Bordetella bronchiseptica) and cattle (Pasteurella
      multocida, Mannheimia haemolytica), respectively, as well as strains causing
      mastitis in dairy cows (Staphylococcus spp., Streptococcus spp., E. coli).
      Determination of the in-vitro susceptibility (minimal inhibitory concentration)
      to at least 17 antimicrobial agents was performed centrally by the BVL using the
      microdilution broth method. The findings approximately match results of an
      analogous study conducted in 2001, and correspondingly revealed significantly
      lower resistance-values in comparison to data published for Germany so far. No
      correlation could be established between the incidence of resistance and
      differing stock densities. By means of the resistance monitoring data gathered by
      the BVL, the risk potential of antimicrobials applied in Germany can be reliably
      defined. This valuable information about the epidemiological situation of
      resistance in Germany can be helpful to veterinarians as a decision guidance when
      choosing appropriate means of therapy. Accordingly, the results stated by the BVL
      are apt to provide an important contribution to improving the safety of food
      animal products. The experiences obtained from the monitoring also show that
      valid data about the antimicrobial susceptibility can only be raised on an
      interdisciplinary approach (federal agencies, county diagnostic laboratories,
      universities, industry). Currently, the BVL put into practice a study with an
      extended spectrum of bacterial species and indications.

PMID- 15584431
TI  - [Distribution of Brachyspira hyodysenteriae and Lawsonia intracellularis in
      healthy and diarrhoeic pigs].
AB  - Although Brachyspira (B.) hyodysenteriae and Lawsonia (L.) intracellularis are
      widely distributed in pigs in Germany, there exists limited information on their
      clinical relevance. To get more insight into their potential role in swine
      diarrhoeal disease, in 2002 and 2003 faecal specimens from healthy pigs (n=1445)
      as well as from diarrhoeic pigs (n=2002) were tested by polymerase chain reaction
      (PCR) for the presence of both agents. Of the specimens from healthy pigs L.
      intracellularis and B. hyodysenteriae were detected in 7.3% and 6.7%,
      respectively. In contrast, of the diarrhoeic pigs the ratios of positive samples
      amounted to 19.4% for L. intracellularis and 17.9% for B. hyodysenteriae.
      Concerning the age of the diseased animals, in growing pigs the detection rates
      of L. intracellularis and B. hyodysenteriae were nearly identical (16.4% and
      14.2%, respectively). In fattening pigs a significant higher number of animals
      were affected with B. hyodysenteriae (35.8%) than with L. intracellularis
      (28.2%). On the other hand, in sows L. intracellularis (35.6% positive samples)
      was dominant compared to B. hyodysenteriae (21.2% positive samples). Considering
      the nearly threefold higher percentage rates of L. intracellularis and B.
      hyodysenteriae in diarrhoeic pigs in comparison to healthy pigs, it is concluded
      that both agents play an important role in swine diarrhoeal disease. The results
      further indicated that in fattening pigs B. hyodysenteriae and in sows L.
      intracellularis have a dominant role, respectively.

PMID- 15584432
TI  - [The prevalence of Yersinia-specific antibodies in cattle in Bavaria].
AB  - Yersiniosis is considered to be an emerging infection in humans. It is believed
      that contaminated pork is the main source of infection for man but also beef and
      cow milk might cause infection in the consumer. Therefore, a survey was carried
      out to obtain actual data on the prevalence of anti-Yersinia antibodies within
      cattle. 600 serum samples were taken form 120 farms located in 43 districts of
      Bavaria, Germany. Antibodies were detected in 396 animals (65.7%) revealing a
      distribution of 52.3% of anti-YopD, 40.3% of anti-YopM, 24.0% of anti-YopH, 21.2%
      of anti-YopE and 3.0% of anti-V-antigen antibodies. 21 reactionpatterns out of 32
      possible patterns were identified. Anti-YopD and YopM antibodies were sufficient
      to detect all Yersinia antibody positive sera. No regional differences in the
      distribution of antibodies were noted.

PMID- 15584433
TI  - [Vaccination strategies for anthrax prevention].
AB  - Apart from live spore vaccines with a certain amount of residual virulence for
      various animal species, there are two acellular protein vaccines for
      immunoprophylaxis against anthrax in humans. For ethical reasons there are no
      experimental data available on the efficacy and duration of the immunity they
      induce in men. Their efficacy was evaluated in laboratory animals, mainly rabbits
      and rhesus monkeys. Furthermore, it is well known that these vaccines elicit only
      partial protection in guinea pigs and almost no protection in mice against a
      challenge with fully virulent spores of Bacillus (B.) anthracis. Other
      disadvantages are the high amount of boosters necessary to elicit and to maintain
      a protective immune response, the variability in the composition of bacterial
      culture supernatants used for production, and the appearance of clinically
      relevant side effects. Therefore, there is ongoing work worldwide to improve the
      existing vaccines by substitution with recombinant antigens and to develop new
      vaccines on the basis of recombinant bacterial or viral live vectors, DNA
      vectors, and by addition of new adjuvants. Special attention is given to
      supplementing the existing toxoid-vaccines with an anti-bacterial component.

PMID- 15584434
TI  - [Toxicological significance of biological markers].
AB  - Biological monitoring or, simply, biomonitoring (BM), refers to the periodic
      measurement of biological markers, or biomarkers (BMKs), in human fluids and
      tissues to assess the interaction (absorption, early health effects,
      susceptibility) between physical, chemical or biological agents and the human
      organism. The primary aim of BM in the workplace is to integrate environmental
      monitoring data and detect early, reversible biochemical or functional changes in
      workers exposed to chemicals before they become clinically relevant. BM also
      contributes to the assessment of chemical risk to workers, as individuals or as a
      group. Biomarkers are generally divided into three main types: biomarkers of
      exposure (BME), response/effect (BMR), and susceptibility (BMS). Other, more
      specific types of biomarkers are those of internal dose (BID), those of
      biologically effective dose (BED) and early biomarkers of disease (EBD). It is
      not always easy, however, to allocate a given BMK--such as the measurement of
      cytochrome P450 phenotype in subjects exposed to organic solvents--to one or the
      other type. Biomonitoring provides several advantages over environmental
      monitoring or health surveillance. For example, it allows an estimate of inter-
      and intra-individual variability in the absorption, distribution and excretion of
      chemicals. It also allows the detection of reversible changes before the
      appearance of a clinically relevant occupational impairment or disease. For these
      reasons, BM has become a routine procedure in occupational health practice
      throughout the world. Even the widely acknowledged, recently updated Code of
      Ethics for Occupational Health Professionals, a milestone in occupational health
      practice, only provides the basic ethical principles associated with biological
      monitoring. The aim of the present paper is to survey the various types of BMK
      available today with two main objectives: to discuss their toxicological
      significance and highlight the substantial differences that exist between their
      use in the practice of occupational health and in medical research. The
      development of new, more valid and reliable BMKs is strongly dependent on the
      understanding not only of the toxicokinetic and toxicodinamic mechanisms of
      chemicals, but also of the various susceptibility factors involved, whether
      genetic or environmental. It is hoped that the concurrent use of BMKs of
      different types may improve chemical risk assessment in workers, both
      individually and as a group.

PMID- 15584435
TI  - [New biomarkers of exposure].
AB  - In this paper we have defined the new biomarkers of exposure (NBE) as those
      biomarkers discovered in the last five years and, among previously validated
      biomarkers, also those applied in different ranges of doses or those determined
      in biological matrices which differ from matrices originally considered. We
      examined the results from the surveys carried out by the main Italian research
      units involved in biological monitoring, i.e. those from the Universities of
      Brescia, Milan, Naples, Padua, Parma, Pavia, Turin and Verona. The data were
      collected using a standardized model and included the following: type of element
      or organic compound, type of biomarker, analytical technique and method, their
      relationship with environmental monitoring data, their relationship with effect
      indicators or effects in general, improvement with respect to old biomarkers,
      reference values. Twenty two NBEs were identified: 14 elements and chemical
      compounds as such or as metabolites, 4 examples of mixtures, 3 of new matrices,
      one of speciation. Among the others, aspects such as interest in requiring NBE,
      quality assurance, availability, cost-benefit ratio were discussed. We conclude
      that development of this specific field of research appears to be a crucial point
      for future improvement in risk assessment and health surveillance procedures.

PMID- 15584436
TI  - [Biologically effective dose biomarkers].
AB  - Biologically effective dose markers--DNA and protein adducts--are classified
      among exposure biomarkers, and are currently used to assess the biologically
      active fraction of xenobiotics, which is capable of interacting with cellular
      macromolecules at the target site. Macromolecular adducts should not only be
      considered as exposure indicators; indeed, their biological significance can also
      be extended to biomarkers of effect and of susceptibility. The achievement of
      such a goal needs research programs aimed both at studying molecular mechanisms
      related to each step along the continuum of events between exposure and disease,
      and at establishing quantitative relationships between exposure levels and adduct
      formation, between adducts and early biological effects, effects and cellular
      structural/functional modifications, leading to the development and eventual
      increase in incidence of specific diseases. Moreover, different factors must be
      considered during data evaluation, such as interindividual variability, the
      background levels of biomarkers in non occupationally exposed population, the
      gradually decreasing doses of genotoxic agents involved in occupational exposure,
      and confounding factors such as diet and smoking habits. Despite the large body
      of literature documenting DNA and protein adduct molecular dosimetry for many
      carcinogen exposures, many authors highlight the need for systematic
      interlaboratory comparison and collaboration by measuring the same biomarkers
      using different techniques and/or different biomarkers related to the same
      exposure levels. There is also general agreement about reducing costs, so that
      dosimetric analyses can become economically more advantageous and accessible in
      all cases where they prove to be useful in preventing health risks.

PMID- 15584437
TI  - [New effect biomarkers].
AB  - The major research goals for researchers developing biomarkers of effect are the
      development and validation of biomarkers that permit the prediction of the risk
      of disease in individuals and groups. One important objective is to prevent human
      cancer. This article reviews the most recent analytical methodologies, validation
      studies and field trials together with auditing and quality assessment of the
      necessary data based on scientific grounds. Consideration is given to new
      developments in the relatively young field of toxicogenomics, possibly leading to
      the identification of early changes that may lead to both cancer and non-cancer
      end points. Although the creation and development of reliable databases
      integrating information from genomic and proteomic research programmes should
      offer a contribution to the prediction of risks and prevention of diseases
      related to chemical exposure, the most promising future application of these
      technologies lies in the molecular diagnosis of diseases whose nosography will
      probably be redefined.

PMID- 15584439
TI  - [Data quality and the interpretation of biological monitoring results].
AB  - Quality assurance criteria are not uniformly applied to routine biological
      determination, in particular with regard to the biomonitoring of exposure to
      organic solvents. Quality assurance is not an abstract concept but rather a
      flexible tool which can be adapted to different situations, such as the
      measurement of different exposure levels or the use of different analytical
      methods, for a range of purposes (routine determination, risk assessment
      procedures, research). The occupational health physician should be actively
      involved in the definition of quality objectives, as well as in checking that
      they have been implemented. This paper deals with some general issues regarding
      quality assurance, and in particular with certain requirements of analytical
      quality (analytical uncertainty, imprecision, bias) and its implementation
      (quality control, reference materials, standardization, reference values),
      contextualized to the biological monitoring of organic compounds and the relative
      metabolites.

PMID- 15584438
TI  - [Individual susceptibility to occupational carcinogens: the evidence from
      biomonitoring and molecular epidemiology studies].
AB  - This paper reviews the literature on the influence of metabolic and DNA repair
      polymorphisms of biological indicators of genotoxic risk commonly used in
      biomonitoring occupational exposure to carcinogens. Genetic polymorphisms which
      influence biomarkers (urinary metabolites, protein and DNA adducts), include P450
      cytochromes (CYPs) and glutathione S-transferases (GSTs) in exposure to
      polycyclic aromatic hydrocarbons (PAHs), and acetyltransferases (NATs) in
      exposure to aromatic amines (AAs). As regards exposure to benzene, also relevant
      is the influence of epoxydohydrolase (EPHX) and NAD(P)H quinone oxidoreductase
      (NQO1) on the urinary excretion of t,t-muconic and phenylmercapturic acids. With
      respect to occupational exposure to styrene, EPHX significantly influences the
      levels of Chromosome Aberrations (CAs), strongly predictive genotoxic biomarkers
      of cancer risk. Some recent studies examine the role of polymorphisms linked to
      DNA repair genes in the modulation of genotoxic risk associated with PAH
      exposure, both for life-style (dietary and smoking behaviour) and for
      occupational reasons. In addition, molecular epidemiology studies (case/control
      studies) of lung cancer in smokers published since 2000 may also be viewed as
      representing models of effects due to exposure to carcinogenic mixtures, some of
      which are present in the working environment (e.g., BaP, benzene, AAs). Almost
      all studies show the clearcut influence (i.e., increased lung cancer risk with OR
      > or = 2) of genetic polymorphisms linked to PAH metabolism (in particular,
      CYPIA1, GSTM1 and P1). Among the risk factors are the different mutagen
      sensitivity towards, for instance, bleomycin and BaP (tested in vitro), the
      reduced repair capacity to DNA damage induced by BaP, and increases in some
      biomarkers of early biological effect (DNA adducts and stable CAs). Other risk
      factors, such as heredity (siblings of cancer patients have a risk factor > or =
      3 with respect to the general population), ethnicity (Chileans > Caucasians;
      Japanese > Americans) and gender (women > men), have still not been clearly
      characterized and these are also reported in this paper. It is clear from the
      above that genetic differences underlie individual susceptibility to lung cancer,
      whether caused by exposure to tobacco smoke or to occupational carcinogens like
      PAHs. Some of these indicators of exposure/individual susceptibility can be
      evaluated in groups at high risk of occupational lung cancer, such as coke-oven
      and aluminium workers and those exposed to coal tar fumes and soot, etc., with
      the aim of identifying subjects who are susceptible due to the high
      concentrations of carcinogens found in their working environment.

PMID- 15584440
TI  - [Biological monitoring and risk assessment].
AB  - Risk assessment in occupational medicine is the part of risk analysis where
      physicians also contribute. A risk is the probability of an adverse health effect
      and derives from the hazard posed by a given chemical and from exposure
      characteristics. Due to the complexity of this process, models are used in
      occupational medicine, where risk factors are identified and exposure estimated,
      combined with an understanding of the severity of possible effects.
      Theoretically, the advantages of biological monitoring are obvious. However, the
      paucity of available data on biological monitoring limits its uses. Moreover, the
      utilization of data on biological monitoring requires evaluation of their
      significance. Examples are discussed to highlight advantages and limitations of
      biological monitoring data in both hazard and risk assessments. They include
      exposure to polycyclic aromatic hydrocarbons, benzene, other carcinogens,
      paraquat and polychlorinated biphenyls.

PMID- 15584441
TI  - [The role of biological monitoring in health and epidemiological surveillance:
      the epidemiological approach].
AB  - A fundamental pre-requisite for the realization of biological monitoring programs
      for health surveillance is the availability of sufficiently accurate tests and
      adequate knowledge of the relationship between biomarkers and health effects. In
      this respect, epidemiology plays an essential role: in conjunction with other
      disciplines (industrial hygiene, toxicology, occupational medicine), it provides
      a conceptual and methodological framework for many biological monitoring
      activities. Compared to biomarkers of dose and effect, susceptibility markers
      (for example, metabolic polymorphisms), for which we have seen an explosion of
      research in recent years, need a specific consideration in that they pose (or may
      pose in a non-remote future) special problems. For different reasons, the use of
      genetic tests for predictive aims at the individual level should now be avoided;
      their use should be restricted to the research field for a better understanding
      of etiopathogenetic mechanisms.

PMID- 15584442
TI  - [Role of biological monitoring in health and epidemiological surveillance: a
      proposal].
AB  - Biological markers can be used at an individual level for medical surveillance or
      at group level within the context of epidemiological surveillance. However, the
      use of biological monitoring for medical and epidemiological surveillance is
      heavily conditioned by the critical issue of biomarker validation. One effective
      means for combining biological monitoring with medical and epidemiological
      surveillance is the mandatory annual report on anonymous and collective data;
      this will be made possible after providing adequate training schemes for the
      occupational physicians involved and the definition of appropriate guidelines,
      aimed at improving the quality of occupational health services. It will then be
      possible to design multicentric surveys to assess the quality of occupational
      health services using validated indicators.

PMID- 15584443
TI  - [Ethical considerations on the planning, assessment and management of biological
      monitoring data].
AB  - If a society aims at preserving its socio-ethical values, practices concerning
      the planning, assessment and management of biomonitoring tests in occupational
      health surveillance and research should not conflict with these values.
      Protecting both health and employment of every candidate or employee must be the
      aim of the occupational health physician. For assessing ethical acceptability of
      occupational health surveillance practices, their accuracy, relevance, need or
      necessity, and consequences must first be analysed. This analysis must constitute
      the basis for any societal democratic decision making process, which cannot be
      substituted for simply by individual informed consent. A physician trained in
      occupational health is the professionalism required for doing the testing and
      assuring the protection of the confidentiality of medical data, in accordance
      with strict legal and deontological rules. In biological monitoring studies and,
      in general, in any occupational health research settings, however, the principle
      of individual, really informed consent must be used, whenever possible. This may
      also considerably contribute to the committment of study subjects to the research
      goals. On the other hand, this committment would also contribute to promoting
      impartial research which is needed to improve the knowledge in occupational
      health and to increase health protection and prevention.

PMID- 15584444
TI  - [Indoor environments, work and health].
AB  - Nowadays, the activities of most of the working population are carried out in
      confined, non-industrial environments such as offices, hospitals, libraries,
      social and leisure centres and means of transport. Sub-optimal air quality in
      these confined spaces can lead to discomfort, ailments and even diseases. The
      impact and diffusion of these effects have led to the organisation and funding of
      large-scale epidemiological investigations in many countries and the nomination
      of working parties by governments, health agencies and international scientific
      societies. Over the past 20 years studies on indoor environments have identified
      sources of risk of various pollutants, established the levels of potentially
      dangerous concentrations and, for most of them, have provided effective measures.
      However, the effects of many biological agents and chemical mixtures still remain
      to be defined and effective guidelines are needed for high quality indoor air.
      Identifying and managing indoor risk factors presupposes a specific methodology:
      the specialist in occupational medicine can play a key role in risk assessment,
      in the early diagnosis of building-related illnesses and in the prevention of
      both short- and long-term effects.

PMID- 15584445
TI  - [Indoor air quality and occupational health, past and present].
AB  - The expression "indoor pollution" of residential, office and public buildings
      appeared for the first time in western societies toward the end of the '60s to
      indicate a complex phenomenon as important to public health as that of the
      "outdoor air pollution" or even more so. The demonstration of the toxic effects
      of passive smoking, radon, and other chemical and biological pollutants present
      in office and residential environments has prompted a wide spectrum of research
      into health risks, has led to position-taking by national and international
      authorities, and has given rise to a new scientific multi-disciplinary field of
      research, with respective international associations, scientific journals, and
      international conferences attended by thousands of participants. In Italy, since
      1988, several scientific conferences have been organised and these have led to
      institutional initiatives such as the Commission set up in 1990 by the Italian
      Environment Ministry and the Commission set up in 1998 by the Italian Ministry of
      Health. The latter produced a Prevention Plan for Health Protection and Promotion
      in Indoor Environments which, for the first time, tackles indoor air pollution in
      a systematic way and provides an overall picture of the health and economic
      impact of the main illnesses related to indoor pollution on society. Decree
      626/94 has also been affected, in some way, by these new scientific findings and
      in art. 33 has produced an update of the old art. 9 of the Decree 303/56. The
      attention to the subject of indoor air quality, in addition to that of offices
      and commercial buildings, has turned in more recent years to special environments
      such as schools and hospitals, resulting in the production of important
      publications. The modern frontier of research on indoor and outdoor air hazards
      is represented by fine air particulate matter. A large number of worldwide
      epidemiological studies have revealed that the daily variation in fine and ultra
      fine particle air concentration in urban areas is associated with the
      simultaneous daily variation in the morbidity and mortality of the general
      population. The particle-linked increase in mortality has been attributed to
      respiratory and cardiovascular toxic effects, but the mechanisms by which urban
      air particles (indoor and outdoor) induce worsening of respiratory and cardio
      vascular diseases are so far unknown and are the subject of intense
      investigation. Workers employed in the tertiary sector (offices, trade, banking,
      hospitals, schools, etc.) now account for 80% of the Italian labour force and the
      occupational physician is increasingly requested to assess the risk and monitor
      the health status of tertiary sector workers. These working environments are
      believed to be healthy and lacking in specific health risk factors, but such a
      belief is often only the result of the limited knowledge that employers, workers
      and the physicians themselves have about these environments and the results of
      international research studies over the last forty years. This issue is surely at
      the centre of the interest of our discipline and of public health throughout the
      developed western world and represents an ongoing challenge for the occupational
      physician, with new research topics and new problems to deal with. Recent issues
      include SARS and the defence of buildings and the air of working environments
      against terrorism attacks, such as the use of anthrax dust.

PMID- 15584446
TI  - [Chemical pollution of indoor air and its effects on health].
AB  - Many studies have demonstrated how exposure to chemical pollutants in indoor air
      has adverse effects on health and comfort. Volatile organic compounds (VOCs),
      formaldehyde, ozone, particulates, fibres and environmental tobacco smoke have
      all been implicated. VOCs include a wide range of chemical substances which
      irritate mucosa. Many are neurotoxic and some are suspected or known to be
      carcinogenic e.g. benzene. Formaldehyde, the simplest and most common aldehyde in
      indoor air, is a powerful irritant to the skin, eyes, nose and upper airways.
      Given its close association with nasal-pharyngeal tumours, it has recently been
      classified as a certain carcinogen for humans. Exposure to ozone may cause airway
      irritation and inflammation, reduce the ventilation function and increase
      reversible bronchial reactivity. In the general population it increases the
      mortality rate and the number of hospital admissions for respiratory diseases.
      Airborne particles, a mixture of organic and inorganic substances, are powerful
      irritants for the eyes and mucosa and can cause adverse cardiovascular effects.
      Apart from indoor environments, exposure to asbestos fibres has been associated
      with an increased risk of respiratory diseases such as pneumoconiosis lung cancer
      and mesothelioma. Synthetic mineral fibres cause transient irritation and
      inflammation of the skin, eyes and upper airways. Recent observations have
      confirmed that exposure to environmental tobacco smoke, which is widespread in
      workplaces, increases the risk of lung cancer, irritative respiratory and ocular
      symptoms and cardiovascular diseases.

PMID- 15584447
TI  - [Biological pollution and allergic diseases].
AB  - House dust mites, pets, microorganisms such as fungi and bacteria are the main
      causes of indoor allergens. The diseases correlated to the presence of these
      allergens are of increasing importance in public health as well as in
      occupational medicine. Indoor allergens are widespread in residential buildings
      as well as in public and in office buildings. Surveys conducted in Italian office
      buildings demonstrated detectable allergen concentrations in most of these
      buildings. In some cases, the concentrations were higher than the proposed risk
      threshold for allergenic sensitisation or for the elicitation of symptoms in
      allergic individuals. The health effects of exposure to indoor allergens mainly
      include allergic asthma and rhinoconjunctivitis caused by IgE reactions in
      predisposed subjects. Moreover, exposure to indoor biological agents can cause
      extrinsic allergic alveolitis or other effects such as the so-called "humidifier
      fever" due to contaminated humidifiers. Standardized methods for the measurement
      of indoor allergen levels are available, and may be useful for the diagnosis and
      treatment of individual allergic patients or for group studies in order to
      evaluate the relationship between allergen indoor levels and health effects or to
      assess indoor allergen levels in private or public buildings for preventative
      purposes.

PMID- 15584448
TI  - [Air quality control systems: heating, ventilating, and air conditioning (HVAC)].
AB  - After a brief illustration of the principal layout schemes of Heating,
      Ventilating, and Air Conditioning (HVAC), the first part of this paper summarizes
      the standards, both voluntary and compulsory, regulating HVAC facilities design
      and installation with regard to the question of Indoor Air Quality (IAQ). The
      paper then examines the problem of ventilation systems maintenance and the
      essential hygienistic requirements in whose absence HVAC facilities may become a
      risk factor for people working or living in the building. Lastly, the paper deals
      with HVAC design strategies and methods, which aim not only to satisfy comfort
      and air quality requirements, but also to ensure easy and effective maintenance
      procedures.

PMID- 15584449
TI  - [Acoustic discomfort in non-industrial indoor environments].
AB  - The number of working activities carried out in non-industrial indoor
      environments that can cause acoustic discomfort is so high that it is impossible
      to deal with all of them here satisfactorily. Therefore, following a briefing
      discussion of the known effects of noise on man, this paper will review the
      current legislation regarding the prevention of occupational noise effects in our
      country today (D.Lgs. 15 Agosto 1991, N. 277), in the light of important changes
      introduced by the EU directive 2003/10/CE. Finally we will discuss the problems
      deriving from exposure to noise on subjects working in offices, in schools, in
      indoor environments for leisure time activities, and in the performance of
      professional music.

PMID- 15584450
TI  - [Lighting condition analysis at work].
AB  - Following a wide review of the national and international technical standards
      which make up the principal reference points when designing illumination systems
      for work areas, the most commonly used methods of photometric analysis are
      examined from both a medical and technical point of view. It can be observed that
      photometric analysis of the work place, which currently is almost exclusively
      based on the measurements of illuminance, does not appear to adequately reach the
      targets set by Occupational Health and Occupational Hygiene, for reasons
      pertaining to the anatomy and physiopathology of the visual function. Moreover,
      the procedures applied to evaluate the workers' subjectivity and/or
      symptomatology, that both in research and during on-site investigations makes use
      predominantly of self-administered questionnaires, shows some shortcomings in
      terms of reliability and validity. In conclusion, it is proposed, especially in
      studies regarding office environments (i) to carry out photometric analysis where
      primary and secondary luminance is always measured and, if light-linked
      subjectivity is required (ii) to make available valid and precise questionnaires
      whose administration be followed by a multivariate data analysis.

PMID- 15584451
TI  - [The quality of non-industrial confined environments: thermal discomfort].
AB  - This paper examines the problem of assessing thermal conditions in moderate
      working environments. Following a brief reminder of the fundamental principles of
      thermal comfort (in terms of balance equation, measurement techniques and indices
      of global and local thermal discomfort), the question of subjective assessment is
      discussed. Finally, a method of evaluation of thermal comfort is proposed.

PMID- 15584452
TI  - [Indoor air quality: suggestions for risk assessment and medical surveillance].
AB  - This paper presents indications for investigations and health surveillance in
      indoor environments. The study of the indoor air quality consists of the
      following phases: acquisition of the necessary information about the indoor
      environment; sampling strategy and techniques; qualitative and quantitative
      analysis of contaminants such as particulate, CO2 and CO, NOx, volatile organic
      compounds, biological agents. The proposed health surveillance is articulated on
      four lines: periodical health surveillance, when already performed for other
      risks (e.g. VDT); specific clinical examinations in occasion of particular
      events; use of a questionnaire for the evaluation of comfort of the workers;
      health promotion. A team approach, with cooperation between technical and medical
      experts, is recommended both for periodical risk assessment and when it is
      necessary to solve specific indoor problems.

PMID- 15584453
TI  - [Acute necrotizing pancreatitis--diagnostic and treatment strategy].
AB  - Despite of the current achievements of medicine, the mortality of necrotizing
      pancreatitis (NP) is still too high--up to 35-40% and stands as a serious
      diagnostic and treatment problem. The results of treatment of 148 patients,
      admitted in the clinic with diagnosis NP, 95 males and 53 females, are discussed.
      The ratio between patients with acute oedematic and acute NP is 81.1% to 18.9%.
      According to the hystopatology findings, the results are as follows: pancreatic
      necrosis--128 patients, peripancreatic necrosis--42 patients, retropancreatic
      necrosis--29 patients, phlegmonous cholecystitis--31 patients. For the exact
      diagnostic estimation of the development and prognosis of NP, we are based on:
      Clinic symptomatology, biochemical constellations (the prognostic scale of
      Ranson), ultrasonography, CT, ERCP, ES, laparoscopy (48 pts), and laparoscopic
      drainage (34 pts) of the abdominal cavity with one or two drains, in order to
      decrease the intoxication and manage intraperitoneal irrigation with antibiotics
      and enzymes. The operative intervations consists of a thorough exploration, broad
      necrectomy combined with lavage and large drainage. COLD (controlled open lesser
      sac drainage) has been performed at 34 cases. In 31 pts cholecystectomy and
      choledochotomy with T-tube drainage of d. choledochus (Kehr drainage) was
      performed. Reoperations have been made at 34 pts (22.9%); in 11 of them--2
      operative revisions have been carried out, in 3 cases--three, and in 3 cases--4
      operative revisions were performed. The total postoperative death rate was 21.6%
      (32 patients). The most common postoperative complications were as follows:
      pulmonary complications at 11 cases, pleural effusions--9 pts, intraabdominal
      abscesses--6 patients, postnecrotic pseudocysts--9 cases, pancreatic fistulas--6
      cases, fistulas of the colon--2 pts, bleeding--4 patients.

PMID- 15584454
TI  - [Renal complications in severe acute pancreatitis].
AB  - Except of the success in the diagnosis and treatment of acute pancreatitis, and
      at present this illness and its complications continue to be actual problem of
      urgent surgery. The object of our study is to establish the frequency of renal
      complications at patients with severe acute pancreatitis and to assess the most
      important risk factors of their development and mortality. MATERIAL AND METHODS:
      The object of our study is 198 patients with severe acute pancreatitis, 75 of
      whom have renal complications.

PMID- 15584455
TI  - [Diagnosis and treatment of perforated pulmonary echinococcosis].
AB  - Pulmonar hydatidosis is widespread disease. It is presented with different
      complications one of which is the perforation of the cyst into the pleural
      cavity. The aim of our research is to share our experience in diagnosis and
      operative treatment of the complications with perforated pulmonary echinococcus.
      MATERIALS AND METHODS: In the study the we have examined 278 patients with
      pulmonary echinococcus, 14 of which have perforation of the cyst into the pleural
      cavity.

PMID- 15584456
TI  - [Algorithms for procedures in thoracic trauma].
AB  - The study includes 1127 injured with thoracic trauma, 23 percent of them with
      polytrauma. The worse thoracic trauma were these with formed flail chest with
      pleural and lung complications, accompanied by severe disfunction in circulation
      and biomechanics of breathing. The application of minimal surgical procedures
      like pleural punctures and drainage of pleural cavities with aspiration achieved
      good results. Thoracotomy was performed on clear indications (unstoppable
      bleeding, large ruptures of lung parenchyma, suppurative lung haematoma, cardiac
      tamponade, rupture of major airways, rupture of diaphragm, rupture of oesophagus
      and coagulated haemothorax). The achieved mortality of 5.9 percent is an
      excellent index suggesting a choice of treatment.

PMID- 15584457
TI  - [A new approach for discovering minimal residual disease in patients with
      operable breast cancer].
AB  - The striving of surgeon for achieving better long-term results of surgical
      treatment of patients with breast cancer put the searching of new independent
      prognostic factors for the exit of the treatment. This has become possible in the
      last decade of XX century when new diagnostic methods as immunochistochemistry,
      polimerase chain reaction (PCR), cytomorphology etc. entered the clinical
      practice. With bone marrow biopsy in patients with breast cancer earlier
      diagnosis of minimal residual disease is achieved, the approach to those patients
      is changed and a possibility for discovering women at higher risk is given. By
      immunochistochemistry method in the diagnostics of minimal residual disease in
      patients with breast cancer, more precise staging is achieved. This will change
      the therapeutic approach to these patients.

PMID- 15584458
TI  - [Complex diagnosis and treatment of hepatic echinococcosis in childhood].
AB  - In dependence of size, localization, observed complications and associated forms
      of disease, the clinical symptomatology is characterized whith a different view.
      Three stages are made out during the illness. Infrequently associated and
      complicated forms of disease are special interest. Surgical treatment is the
      basic method of treatment in hydatidosis. It's specificity at children keeps
      special because of age. The surgery of the hydatidosis has been simpified and
      except for some cases. Surgical procedurs is great variability of pathology amond
      hydatid cyst, logically a inform treatment can not be recommended. Surgical
      approaches were: 1. Conservative methods--leaving of pericyst in situ; or 2.
      Radical methods--total pericystectomy of liver resection. Modern surgical
      treatments must be individualized for each cases.

PMID- 15584459
TI  - [Research on the problems of recurrence in childhood hydatidosis].
AB  - One of the very important problems in hydatidosis in childhood is the problems to
      diagnosed recidives, their ethyology and treatment. In diagnosing such cysts
      intraoperative ultrasonography is considered as absolutely necessary and
      mandatory. After surgery treatment for complicated and fertiled cyst, dispensary
      outpatient observation and chemotherapy of the hydatid disease are recommended
      with a view to promote radical cure. We observed a higher rate of recidives in
      conservative methods than in radical ones.

PMID- 15584460
TI  - [Clinical and microbiological characteristics of nosocomial infections according
      to material of the IIIrd Surgical Clinic, UMBAL "St. George"--Plovdiv, over a 10
      year period].
AB  - As a nosocomial (NI) infection we describe this one acquired in hospital due to
      proper conditions for spreading of virulent microbes. This is old problem with
      new vision in the field of use of powerful antibiotics and fast growth microbial
      resistance. AIM OF THE STUDY: To make an retrospective clinical investigation
      about the rate, type and etiology of NI as well as duration and outcome of
      treatment in our clinic and to compare the data with these quoted in literature.
      MATERIAL AND METHODS: We use hospital charts about the period of 1990-1999.
      Distribution of NI types was according to CDC criteria. RESULTS: For the period
      were operated on 14 932 patients. In 918 (6.15%) of them a NI was diagnosed. Sex
      ratio was 56% (514) man and 44% (404) women with a mean age of 56 years. After
      the treatment of patients with NI 86.48% (805) of them got better. 13.52% (102)
      were with unsuccessful treatment and got lethal exit. In 78 (76.47%) of death
      patients a pneumonia NI was developed. 633 antibiograms were received with 63.03%
      monoinfections and 22.59% polyinfections. In 91 cases smears were sterile.
      CONCLUSIONS: NI are one of the reasons for prolonged hospital stay and death of
      patients although fast development of pharmacy and new antimicrobial agents. It
      was centered on their prophylaxis.

PMID- 15584461
TI  - [Mirizzi syndrome (literature review)].
AB  - In this reivew the historical aspects are presented about the sindroma of
      Mirrizi. It's forms and pathogenesis are described. We define the modern imaging
      techniques of diagnose--ultrasonography, ERCP, CT, MRI as well as the mandatory
      intraoperative cholangiography. A number of classifications of the sindroma are
      discussed, which are the guide of the surgical stategy, surgical and non-surgical
      methods of treatment.

PMID- 15584462
TI  - [Endovascular prostheses].
AB  - Endovascular grafts are transluminally implanted vascular devices that combine a
      vascular stent with a "prosthetic cover" and are designed for use as a less
      invasive treatment of vascular disease. Indications include aneurysms,
      arteviovenous fistulas, dissections, traumatic vascular lesions, and vascular
      occlusions. High risk patients with severe co morbidities are candidates for
      endoluminal grafting. Specific complications peculiar to stent-grafts have been
      described. Early and midterm results demonstrate that endovascular grafting is a
      safe and promising treatment modality. Concurrent comparative studies, randomized
      trials and registries will be needed to evaluate long-term efficacy of those
      devices.

PMID- 15584463
TI  - [Multiple primary malignant neoplasms (MPMN), with case reports].
AB  - In this work the authors reviewed the literature on multiple primary malignant
      neoplasms (MPMN). This termin includes two or more tumours with different
      histologic appearance developing in different organs and giving metastases. The
      authors present 4 case reports of MPMN payng particular attention on the
      importance of the correct diagnosis of the tumours for the treatment of the
      patients.

PMID- 15584464
TI  - [Disseminated malignant melanoma, complicated with upper-digestive hemorrhage].

PMID- 15584465
TI  - [Endometriosis of the cecum leads to acute intestinal obstruction].

PMID- 15584466
TI  - [Community Nutrition].
AB  - In the last 20 years, Public Health Nutrition focused mainly on the qualitative
      aspects which may influence the onset of chronic diseases, quality of life,
      physical and mental performance and life expectancy. This applied knowledge
      organised as part of preventive and health promotion programs led to the
      development of Community Nutrition. The aim of Community Nutrition actions is to
      adequate lifestyles related to food consumption patterns in order to improve the
      quality of life and contribute to health promotion of the population in the
      community where programs and services are delivered. Key functions to develop in
      a Community Nutrition Unit consist in the identification and assessment of
      nutrition problems in the community as well as the design, implementation and
      evaluation of intervention programs by means of appropriate strategies. These
      should aim at different populations groups and settings, such as work places,
      schools, high risk groups or the general public. Nowadays, Community Nutrition
      work efforts should focus on three main aspects: nutrition education in schools
      and in the community; food safety and food security and the development and
      reinforcement of food preparation skills across all age groups. Social catering
      services, either in schools, the work place or at the community level, need to
      ensure adequate nutritional supply, provide foods contributing to healthy eating
      practices as well as to enhance culinary traditions and social learning. Food
      safety and food security have become a top priority in Public Health. The
      concepts referes to the availability of food safe and adequate as well as in
      sufficient amount in order to satisfy nutrition requirements of all individuals
      in the community. Social changes along new scientific developments will introduce
      new demands in Community Nutrition work and individual dietary counselling will
      become a key strategy. In order to face new challenges, community nutrition
      pactitioners require a high quality profesional training.

PMID- 15584467
TI  - [School-based education strategies to promote fruit and vegetable consumption:
      the Pro Children Project].
AB  - Available population data suggest that a high proportion of European children and
      young people eat less fruit and vegetables than desirable. School based health
      promotion strategies fostering healthy eating practices and regular physical
      activity has the potential for a major impact on health and wellbeing during
      childhood and later stages in life. The aim of Pro-Children project is to
      estimate the consumption of fruit and vegetables as well as its main determinants
      among 11 year old European children and their families. It also aims to develop
      and assess the effectiveness of a school-based intervention program to promote
      adequate consumption levels of fruit and vegetables among school children. In the
      first phase of the project, cross-sectional studies were carried out on random
      population samples in nine European countries. The study protocol included
      assessment of fruit and vegetable consumption and a questionnaire to ascertain
      key determinants. A school-based intervention program was designed based on the
      Attitude, Social Influence and Self-Efficacy model (ASE). Theoretically similar
      but culturally relevant interventions were designed to be tested in Norway, The
      Netherlands and Spain during two school years. Each intervention site follows-up
      10 intervention schools implementing the program and 10 control schools.
      Intervention planning and design followed an intervention mapping procedure. Key
      behaviours and determinants to be addressed through the intervention were
      identified in order to develop a matrix of educational objectives. The provision
      of fruit and vegetables in the school is an outstanding element. Program
      activities include guided classroom activities, computer tailored messages for
      children, activities to be completed at home with the family and family targeted
      specific actions. Additionally, optional components for community reinforcement
      include mass media, school health services participation and implication of
      grocery stores in the project. Despite cultural and social diversity, common
      school-based strategies to increase fruit and vegetable consumption among
      children are feasible across Europe. Understanding specific situations will
      enhance implementation and gain support.

PMID- 15584468
TI  - [Determinants of success in nutrition and food security programs].
AB  - To gain a better understanding of factors which determine the effectiveness,
      efficiency and sustainability of community-based food and nutrition programmes,
      FAO has developed a conceptual framework and methodology to analyze these
      programmes. Based on selection criteria, 9 case studies were carried out in Latin
      America, Africa and Asia. The success factors associated with programme
      efficiency were analyzed in terms of these factors: enabling political
      environment; continuous awareness processes; community participation in programme
      planning, implementing and monitoring; measurable and time-bound objectives,
      management capacity of the programmes; participation of local non-governmental
      organizations; provision of basic services; association between the local
      government and the community to facilitate the shared ownership of the programme;
      and financial and technical arrangements necessary to ensure the sustainability
      of the results. Based on the lessons learned, FAO has elaborated a practical
      guide to analyze the community-based food and nutrition programmes, with the view
      to improve their efficiency and impact and to strengthen the analytical capacity
      of all those involved in programme design and analysis.

PMID- 15584469
TI  - [Nutrition intervention actions in relief situations: report on 4 experiences in
      Mexico].
AB  - In the last years Mexico faced several natural and human provoked disasters. We
      choose the Mexico City earthquake, the Chichonal volcano eruption, the Guatemala
      war and its refugees and the Chiapas armed movement. In all of them the INCMNSZ
      surveillance system proposal has been applied. To establish the intervention we
      classified the emergencies according to its magnitude and localization. The
      intervention consisted in: immediate attention of serious cases, immunizations,
      quimioprofilaxis, personal hygiene, environment control, nutritional assessment
      and diet definition. The affected population attended were: in the eruption
      4.500, in the earthquake 1.000, in the Guatemala war 19.000 and in the Chiapas
      movement 6.940. Population damaged by the eruption and the war received mass
      feeding; complementary feeding (vulnerable groups) and therapeutic feeding
      (people with tuberculosis and serious undernutrition). In the earthquake people
      received first, prepared food and later they were organized to bring, plan,
      prepare and distribute their food. In the Chiapas armed movement people received
      only special baby food. In all cases, population also receive nutritional
      information and only with the refugees and the Chiapas damaged people the local
      food production was promoted. We suggest evaluating every emergency program and
      share experiences to afford this type of situations in a better way.

PMID- 15584470
TI  - [A methodological proposal to include nutrition education in primary schools.
      Experience in Chile].
AB  - This article presents the methodology to incorporate nutrition education in
      Chilean primary schools. In 2001, nutritional status, food and nutrition
      knowledge, attitudes and practices of 1701 school children from ten urban and
      rural public schools (3rd to 7th grade) were evaluated. This information was
      necessary to design the nutrition education strategy. The prevalence of obesity
      was 15.4% and overweight 19.6%. Daily intake of dairy products, fruits and
      vegetables was low, while the consumption of energy dense snacks was very high.
      Because the Ministry of Education does not allow the incorporation of new
      programs to the curriculum, the educational strategy was based on the development
      of a text book, a teacher's guide, five practical guides for students from third
      to eight grade and a CD-Rom. These materials were validated by 36 teachers
      through an educational intervention during 5 months in six schools (intervention
      groups). The teachers reported that the educational materials were useful,
      motivational and easy to understand for both, teachers and students. Preliminary
      results showed a significant increase in food and nutrition knowledge, in the
      consumption of dairy products and a decrease in the consumption of bread among
      the intervention groups. Intake of snacks increased in both groups, but it was
      significantly higher in the control group. These results indicate that nutrition
      education will only produce significant changes in food habits if health and
      educational authorities establish regulations for food advertisement oriented to
      children and also to food items sold in the schools.

PMID- 15584471
TI  - [Best practices in Community Nutrition: challenges and commitments].
AB  - Community Nutrition is a science in continuous evolution that needs to be adapted
      to changing nutritional problems and to geographical, cultural and socieconomical
      diversity. Best practices in community nutrition is a concept that facilitates
      enhanced diffusion and application of knowledge through the analysis of properly
      designed, executed and evaluated experiences. The conclusions of the five
      presentations in the session organized by the Spanish Society of Community
      Nutrition at the XIII Latin American Conference on Nutrition are analyzed. Also,
      the major challenges and commitments are described: planning and forecasting,
      intersectorial collaboration, international cooperation, evaluation and
      monitoring, empowerment, training, fostering institutional support, community
      participation, leadership, sustainability, continuity, transparency and
      dissemination. The needs to further develop cooperation and sharing of
      experiences in the area of community nutrition between Latin America and Spain is
      highlighted.

PMID- 15584472
TI  - [Mediterranean diet. Characteristics and health benefits].
AB  - The purpose of this article is to define the concept of Mediterranean Diet or
      Diets and to describe the associated health benefits recognised by the scientific
      community. The characteristics of the Mediterranean Diet are described as well as
      the effects the foods comprising it have on the most common pathologies such as
      cardiovascular disease and cancer. The Spanish Society of Community Nutrition's
      consensus based Healthy Diet Pyramid, along with Greece's pyramid for food
      guidelines for the adult population (from the Greek Ministry of Health), are
      presented and compared. They are the graphic representation of the food and
      physical activity guides of two typically Mediterranean countries. Nutritional
      and sociological trends are also discussed and their impact on the evolution of
      the Mediterranean Diet.

PMID- 15584473
TI  - [Wheat, bread and pasta in Mediterranean diets].
AB  - Cereals in diets have varied along evolution trends in food patterns. Cereals are
      starchy foods and are the main source of polysacharides in the diet. In
      Mediterranean countries, cereals have been used in different ways, though they
      are mainly used as refined cereals. Wheat bread is one of the most commonly used.
      In the average Spanish diet, considerable changes have taken place since 1961
      leading to a significant decrease in percent energy from carbohydrate. At the
      same time, percent energy from fat has increased as web as protein intake. These
      changes in the nutritional pattern reflect a continuous decrease in consumption
      of grains and cereals, pulses and potatoes. In the last decades, consumption of
      pasta however has increased as web as consumption of processed bakery products
      and biscuits. Scientific and epidemiological evidence show that cereals should be
      the main source of energy in the diet, in line with the so-called Mediterranean
      Diet. Polysacharides should provide 50-55% energy. In order to reach that goal,
      cereal, legumes and potatoes should be included in the daily diet as 4-6
      portions. Whole grain cereales should be preferred or food preparations combining
      pasta, potatoes or rice with vegetables in order to reduce the glycemic index.
      Processed bakery products and biscuits should be consumed in moderation.

PMID- 15584474
TI  - [The quality of fat: olive oil].
AB  - Olive oil is one of the most characteristic Mediterranean Diet foods, also being
      a key contributor to the healthy aspects attributed to this dietary pattern.
      Since 4000 BC, olive oil has been obtained in the Mediterranean area, but now it
      is exceeding its natural borders, and currently the use of olive oil is a
      worldwide synonym of health and gastronomic quality. Olive oil has important
      effects on the body, and has protective effects against several pathologies, i.e.
      cardiovascular diseases, and various cancers, as well as to diminish the age
      related cognitive decline. These effects are due to the olive oil richness in
      monounsaturated fatty acids and antioxidant substances. Olive oil has been and is
      the food that define one of the most oldest methods of cooking: frying.

PMID- 15584475
TI  - [Fruits and vegetables].
AB  - Fruits and vegetables are particularly interesting for health for their content
      in minerals, antioxidant vitamins, phytochemicals and dietary fiber. All these
      substances are related to lower risk for the development of health probems, such
      as certain types of cancer, cardiovascular diseases, type 2 diabetes, obesity,
      constipation or diverticolsys. The sound basis of scientific evidence led
      European and American scientific organizations and societies to recommend an
      intake up to 150-200 g of vegetables every day; ie. 2 or more portions daily and
      3 or more portions of fruit; five portions of fruit and vegetables all together.
      According to the consumer panel from the Spanish Ministry of Agriculture,
      Fisheries and Food, between the late 80s and the end of the 90s. consumption of
      fruit and vegetables decreased. However, in late years this trend has slow down
      and even reversed. Results from food consumption studies based on individual
      level assessment in Spain estimate an average consumption of fruit and vegetables
      of 154 g/per person/day in adults aged 25-60 yr. Prevalence of inadequate intake
      of fruit and vegetables is high among children and young people. In this age
      group above 70% of the population consume less than 3 portions of fruit every day
      on average. Reorientation of prevailing food patterns nowadays require investment
      in measures aimed at increasing the consumption of plant foods and estimulate
      healthy food habits in families.

PMID- 15584476
TI  - [Mediterranean Diet and the sea: fishes].
AB  - The excellent quality of the Mediterranean Diet, apart from other products, is
      associated to a high consumption of fish. Epidemiological studies have shown over
      time certain beneficial effects of fish consumption in the prevention of chronic
      diseases. The specific components found in fish, the long chain omega 3
      eicosapentanoic and docosahexanoic fatty acids, have been identified as the
      principle elements responsible for this protective effect in Mediterranean
      populations. There is also evidence for a relationship between elevated fish
      consumption and reduced cardiovascular mortality, especially in populations at
      greater risk for this disease or those with high fatty fish intakes. Moreover,
      fish consumption of > or = 3.5 servings/week appears to have a protective effect
      against certain site specific cancers, and is also associated with a number of
      lifestyle factors. It's been shown that this protective effect is reduced in
      those who smoke, consume alcohol, are less physically active and who consume fish
      preserved in salt. However, these preventive effects are seen fundamentally when
      lipid profiles approximate those typical of the Mediterranean Diet, which is also
      rich in monounsaturated fatty acids. In light of new evidence, current
      nutritional objectives for the Spanish population recommend that polyunsaturated
      fatty acids account for 5% of total calories, with an omega6:omega3 ratio ranging
      from 6/1 to 10/1.

PMID- 15584477
TI  - [Yoghurt: a probiotic Mediterranean food].
AB  - Yoghurt is a traditional Mediterraean food, based on milk and specific living
      cultures. Most recent research shows that yogurt bacteria are able to survive
      passage through the human intestine. Yogurt containing viable starter cultures
      has been shown to improve lactose digestion in lactose-intolerant people. There
      are indications for a role of live yogurt cultures in modulating the immune
      system of the consumer. Long-term consumption of live yogurt reduces nasal
      allergies, particularly in young adults.

PMID- 15584478
TI  - [Wine in Mediterranean Diet].
AB  - Wine is considered a food whose history has intertwined with human culture. The
      first data of wine presence is from 7000 years ago, from Iran. Besides along
      history, references about drinking wine in moderation could be healthier were
      published, it is in 1992 when the paper of French Paradox is published when stars
      the real interest for scientific community to study the components of wine with
      beneficial effect. The components that have been considered are ethanol and
      polyphenolic compounds. Here we include a review of the effect of these compounds
      in human body.

PMID- 15584479
TI  - [Nutrient content and health effects of nuts].
AB  - Nuts are foods with a high energy density, due in part to its small water
      content. They also present a low saturated fat content (<7%) but a high
      unsaturated fat contribution (40-60%). They represent one of the richest sources
      of dietary fiber, which is basically of the insoluble type. The effects of nut
      intake on health have been widely studied. Several prospective epidemiological
      studies performed on large cohorts have consistently shown that regular
      consumption of small amounts of nuts is negatively related to the risk of
      cardiovascular disease and to the risk of cardiovascular or all-cause mortality.
      From these studies can be concluded that regular consumption of small amounts of
      nuts leads to a 30-50% reduction in the risk of cardiovascular disease.
      Additionally, intervention studies have shown a positive effect of nut intake on
      lipid profile with significant reductions in total and LDL cholesterol levels and
      small or null effects on the HDL fraction. More recently, some studies have
      focused on the effect of nuts on body weight. At present, no evidences support a
      detrimental effect of nut consumption on body weight. On the contrary some weight
      loss studies suggest a beneficial effect of nut intake on body weight regulation.

PMID- 15584480
TI  - [Are there any nutritional deficiencies in the Mediterranean Diet?].
AB  - The Mediterranean diet has been described as a model from a nutritional and
      sanitary point of view due to the proportion in which it includes all the food
      groups. Nevertheless, in the last few years changes in lifestyle have triggered a
      move away from the recommended intakes in relation to several nutrients. The
      intake of cereals and vegetables has decreased particularly, while the intake of
      fats and animal products has increased. The reduced energy expenditure associated
      with a sedentary lifestyle and the quest for beauty in the form of thinness led
      to a restricted energy intake. All these changes make it even more difficult to
      ensure adequate intakes of vitamins and minerals. The Spanish population has
      problems particularly with vitamins A, D, E, B2, B6 and folic acid, as well as
      with intake of minerals, which is below recommended values. This problem is most
      clearly seen in certain groups: women, the elderly, children, gestating and
      lactating women, ill people, smokers and those under regular medication. Knowing
      the extent of this reality can be the first step towards the introduction of
      correcting measures or to initiate campaigns to inform the consumer about the
      necessary changes in the diet and about the characteristics of the Mediterranean
      diet which are being lost and should be restored.

PMID- 15584481
TI  - Increased frequencies of serum antibodies to neurofilament light in patients with
      primary chronic progressive multiple sclerosis.
AB  - We investigated whether serum and cerebrospinal fluid (CSF) antibodies to the
      light subunit of the NF protein (NF-L), a main component of the axonal
      cytoskeleton, may serve as biological markers for axonal pathology and/or disease
      progression in multiple sclerosis (MS). IgG to NF-L was measured in sera and CSF
      of MS patients, patients with inflammatory demyelinating diseases of the PNS,
      with acute inflammatory neurological diseases (including bacterial and viral
      meningitis), with neurodegenerative diseases, with acute noninflammatory
      neurological diseases (including stroke, headache and backache) and healthy
      controls by enzyme-linked immunosorbent assay. We found that serum anti-NF-L IgG
      antibodies were significantly elevated in MS patients with primary progressive
      disease course and we provide evidence for an intrathecal production of these
      antibodies. Our findings support the use of serum antibodies to NF-L as a marker
      for axonal destruction.

PMID- 15584482
TI  - Estimation of the macromolecular proton fraction and bound pool T2 in multiple
      sclerosis.
AB  - This study used a model for magnetization transfer (MT) to estimate two
      underlying parameters: the macromolecular proton fraction (f) and the bound pool
      T2 (T2b) in patients with multiple sclerosis (MS). Sixty patients with clinically
      definite MS and 27 healthy controls were imaged using: (1) a dual echo fast spin
      echo sequence, (2) a MT sequence (with ten MT power and offset frequency
      combinations) and (3) proton density and T1 weighted sequences (for T1 relaxation
      time estimation). Fourteen normal-appearing white matter (NAWM) regions of
      interest (ROI) and six normal-appearing gray matter (NAGM) ROIs were outlined in
      all subjects. Lesions were also contoured in subjects affected by MS. The model
      was fitted to the data leading to estimates of T2b and f. Results showed that T2b
      was increased in lesions whereas f was reduced. In NAWM, f was decreased while
      T2b was only increased in secondary progressive MS. NAWM f correlated modestly
      with disability. Further studies are needed to investigate the pathological basis
      of the abnormalities observed.

PMID- 15584483
TI  - CD45 (PTPRC) as a candidate gene in multiple sclerosis.
AB  - The 77C-->G polymorphism in exon 4 of CD45 or protein tyrosine phosphatase
      receptor-type C (PTPRC) has been investigated in families with multiple sclerosis
      (MS) and in several cohorts of sporadic patients and controls, however, with
      conflicting results. To better understand the role of this functionally important
      polymorphism in MS, we investigated the transmission of the 'G' allele from
      unaffected parents to their affected children in 176 families by using linkage
      and association statistics. The 'G' allele was transmitted to the affected
      offspring in five of the seven pedigrees carrying this allele and the TRANSMIT
      program detected association with a P=0.0342. We conclude that the 77C-->G PTPRC
      polymorphism is present and preferentially transmitted in a small subgroup (<5%)
      of MS families, which may only be detected with complementary methods of
      analysis.

PMID- 15584484
TI  - Genetic analysis of SLC11A1 polymorphisms in multiple sclerosis patients.
AB  - Solute carrier 11a1 (SLC11A1; formerly NRAMP1, where NRAMP stands for natural
      resistance-associated macrophage protein) is a proton/bivalent cation antiporter
      that localizes to late endosomes/lysosomes. SLC11A1 regulates macrophage
      functions that are of potential importance in the induction and/or maintenance of
      autoimmune diseases such as rheumatoid arthritis, type I diabetes and Crohn's
      disease. We investigated SLC11A1 gene as a candidate gene for genetic
      susceptibility to multiple sclerosis (MS) in our population. Four SLC11A1 gene
      polymorphisms (5'GT repeat, D543N, 1729 + 55del4 and 1729 + 271del4) were
      analysed in a case-control study of 195 patients with MS and 125 control
      subjects. We found no evidence of association between SLC11A1 polymorphisms and
      MS susceptibility in the Spanish population.

PMID- 15584485
TI  - Multiple sclerosis in women having children by multiple partners. A population
      based study in Denmark.
AB  - We investigated whether having children with multiple men is a risk factor for
      being diagnosed with multiple sclerosis (MS). We studied a cohort of 151,328
      women, of whom 64,704 had different men fathering their children and 86,624 the
      same partner for all births. Women were included if they had a second or higher
      parity child between 1973 and 1996. The follow-up for MS ended in 1997. There
      were a total of 213 cases of MS diagnosed during the study period. We analysed
      data through Poisson regression models. Women having children with different men
      were not at higher risk of being diagnosed with MS, with the possible exception
      of a short period after having a baby with a new partner. Women having children
      with more than one man may have a higher risk of a pregnancy accelerating the
      diagnosis of MS but are probably not at an overall higher risk of MS.

PMID- 15584486
TI  - The unique impact of changes in normal appearing brain tissue on cognitive
      dysfunction in secondary progressive multiple sclerosis patients.
AB  - OBJECTIVE: The purpose of this study was to examine the relationships between
      cognitive functioning, whole brain magnetic transfer ratio (MTR) imaging,
      supratentorial 1H-magnetic resonance spectroscopy imaging (1HMRSI), and
      conventional T1 and T2 imaging in a homogenous sample of SPMS patients. METHODS:
      Nineteen patients underwent a single 90-min imaging session that obtained T1-and
      T2-weighted images and MTR. 1HMRSI was obtained on 14 of these patients. Patients
      underwent a neuropsychological battery, which was used to create an integrated
      measure of cognitive impairment. Cognitive impairment was the dependent variable
      in two hierarchical multiple regression analyses in which T2 lesion load, T1
      lesion load, and MTR or NAA/Cr were entered sequentially. RESULTS: MTR was
      significantly related to cognitive functioning (deltaR2 = 0.22, P = 0.02) after
      accounting for T2 lesion load (deltaR2 = 0.33, P = 0.01) and T1 lesion load
      (deltaR2 = 0.00, P = 0.98). NAA/Cr was not significantly related to cognitive
      functioning. CONCLUSIONS: Cognitive dysfunction may act as a clinical marker of
      normal appearing brain tissue pathology in multiple sclerosis.

PMID- 15584487
TI  - IFN-beta treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production
      in patients with relapsing-remitting multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system probably mediated by Th1 lymphocytes. IFN-beta is an established therapy
      for relapsing MS patients, although the mechanisms underlying its efficacy are
      yet to be well characterized. We determined IL-2 production, CD25 expression and
      T-cell proliferation from relapsing-remitting MS patients before and three months
      after starting therapy. A decrease in the percentage of CD80-induced IL-2
      producing cells was observed after in vivo IFN-beta treatment. These data support
      that one of the immunomodulatory effects of IFN-beta treatment in MS may be a
      limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.

PMID- 15584488
TI  - A randomized open label study of pain medications (naproxen, acetaminophen and
      ibuprofen) for controlling side effects during initiation of IFN beta-1a therapy
      and during its ongoing use for relapsing-remitting multiple sclerosis.
AB  - Multiple sclerosis (MS) patients initiating IFN beta-1a, Avonex, therapy (Group
      1, n = 30) or experiencing side effects after 6 months on therapy (Group 2, n =
      30) were randomized for 5 weeks open label adjunct therapy to naproxen (Aleve),
      acetaminophen (Tylenol) or ibuprofen (Advil). Our hypothesis was that non
      prescription pain medications are effective in decreasing or alleviating the side
      effects associated with IFN beta-1a therapy. Contrary to the hypothesis, most
      patients in both groups continued to report side effects on all pain medications.
      After 5 weeks, headache, fever, chills and injection site pain were low in < or =
      50% of patients. Moderate to significant fatigue, muscle or joint pain continued
      in most patients. As a quality of life measure, the Modified Fatigue Impact Scale
      (mFIS) improved for Group 1 on naproxen or ibuprofen with greatest improvement in
      physical subset (P = 0.002 for naproxen and P<0.01 for ibuprofen). Total mFIS for
      Group 1 on acetaminophen improved (P = 0.04) due to improved cognitive subset
      rather than physical subset. Group 2, with side effects initially, reported less
      significant fatigue (severity 5-10) but more moderate fatigue (severity 2-4) at
      study end for all three medications. All medications improved cognitive subset (P
      = 0.05). Physical mFIS subset did not improve for Group 2 on acetaminophen, but
      did with naproxen (P = 0.05) or ibuprofen (P = 0.03). Naproxen and ibuprofen were
      more effective than acetaminophen in minimizing physical side effects of IFN beta
      1a. None of the three pain medications tested were as effective as hypothesized
      for minimizing fatigue or muscle and joint pain.

PMID- 15584489
TI  - Decisional role preferences, risk knowledge and information interests in patients
      with multiple sclerosis.
AB  - OBJECTIVE: Shared decision making is increasingly recognized as the ideal model
      of patient-physician communication especially in chronic diseases with partially
      effective treatments as multiple sclerosis (MS). To evaluate prerequisite factors
      for this kind of decision making we studied patients' decisional role preferences
      in medical decision making, knowledge on risks, information interests and the
      relations between these factors in MS. METHODS: After conducting focus groups to
      generate hypotheses, 219 randomly selected patients from the MS Outpatient Clinic
      register (n = 1374) of the University Hospital Hamburg received mailed
      questionnaires on their knowledge of risks in MS, their perception of their own
      level of knowledge, information interests and role preferences. RESULTS: Most
      patients (79%) indicated that they preferred an active role in treatment
      decisions giving the shared decision and the informed choice model the highest
      priority. MS risk knowledge was low but questionnaire results depended on disease
      course, disease duration and ongoing immune therapy. Measured knowledge as well
      as perceived knowledge was only weakly correlated with preferences of active
      roles. Major information interests were related to symptom alleviation,
      diagnostic procedures and prognosis. CONCLUSION: Patients with MS claimed
      autonomous roles in their health care decisions. The weak correlation between
      knowledge and preferences for active roles implicates that other factors largely
      influence role preferences.

PMID- 15584490
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates
      experimental autoimmune encephalomyelitis by suppressing the functions of antigen
      presenting cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a 38-amino acid
      neuropeptide belonging to the secretin-glucagon-vasoactive intestinal peptide
      (VIP) family, performs a variety of functions in both the nervous and immune
      systems. In this study, we examined the effects of PACAP on experimental
      autoimmune encephalomyelitis (EAE) in C57BL/6 mice. When administrated
      intraperitoneally every other day after immunization with myelin oligodendrocyte
      glycoprotein (MOG) peptide 35-55, PACAP ameliorated both the clinical and
      pathological manifestations of EAE Ex vivo examination revealed a significant
      inhibition of MOG35-55-specific Th1 response in mice treated with PACAP. In vitro
      analysis revealed that PACAP suppressed the production of inflammatory cytokines,
      including TNF-alpha, IL-1beta, and IL-12, and expression of the costimulatory
      factor B7-2 on macrophage and microglia, which may function as antigen presenting
      cells (APC) in the CNS. While PACAP suppressed the differentiation of MOG35-55
      specific T cells into Th1 effectors upon restimulation with MOG35-55-expressing
      APC, it did not affect interferon (IFN)-gamma production by MOG35-55-specific T
      cells stimulated with anti-CD3 and anti-CD28. These observations suggested that
      PACAP suppressed induction of EAE primarily via suppression of APC function and
      inflammatory cytokine production. PACAP may be useful in the future treatment of
      Th1-mediated autoimmune diseases, such as multiple sclerosis.

PMID- 15584491
TI  - Nursing home residents with multiple sclerosis: comparisons of African American
      residents to white residents at admission.
AB  - This research profiles African American residents with multiple sclerosis (MS) at
      admission to the nursing facility and compares them to profiles of white
      residents with MS using the Minimum Data Set (MDS). We analysed MDS admission
      assessments for 1367 African Americans with MS and 9294 whites with MS. African
      American residents with MS were significantly younger at admission than white
      residents with MS, with almost one half of these African Americans 50 years or
      younger compared to only one quarter of these whites. African American residents
      with MS were significantly more physically disabled and cognitively impaired at
      admission than white residents with MS. Although there were significant racial
      differences in disability, there were no significant racial differences among
      these MS residents in the use of various therapies provided by qualified
      therapists. These observed racial differences among MS residents in disease
      manifestations, severity, progression and disability are due to multiple
      variables and point out the need for more research. By combining discoveries from
      genetics, immunology, epidemiology and virology we can gain a better
      understanding of the complex pathophysiology of MS and develop more effective
      treatments and preventive measures. Our findings also indicate potential racial
      disparities in the use of MS-related care, illustrating that a greater outreach
      effort may be needed to evaluate and treat African Americans with MS.

PMID- 15584492
TI  - Resistance training improves strength and functional capacity in persons with
      multiple sclerosis.
AB  - The purpose of this study was to evaluate the effect of an eight-week progressive
      resistance training programme on lower extremity strength, ambulatory function,
      fatigue and self-reported disability in multiple sclerosis (MS) patients (mean
      disability score 3.7 +/- 0.8). Eight MS subjects volunteered for twice weekly
      training sessions. During the first two weeks, subjects completed one set of 8-10
      reps at 50% of maximal voluntary contraction (MVC) of knee flexion, knee
      extension and plantarflexion exercises. In subsequent sessions, the subjects
      completed one set of 10-15 repetitions at 70% of MVC. The resistance was
      increased by 2-5% when subjects completed 15 repetitions in consecutive sessions.
      Isometric strength of the quadriceps, hamstring, plantarflexor and dorsiflexor
      muscle groups was assessed before and after the training programme using an
      isokinetic dynamometer. Magnetic resonance images of the thigh were acquired
      before and after the exercise programme as were walking speed (25-ft), number of
      steps in 3 min, and self-reported fatigue and disability. Knee extension (7.4%),
      plantarflexion (52%) and stepping performance (8.7%) increased significantly (P <
      0.05). Self-reported fatigue decreased (P < 0.05) and disability tended to
      decrease (P = 0.07) following the training programme. MS patients are capable of
      making positive adaptations to resistance training that are associated with
      improved ambulation and decreased fatigue.

PMID- 15584493
TI  - Reliable screening for neuropsychological impairment in multiple sclerosis.
AB  - In an earlier study, we developed the Multiple Sclerosis Neuropsychological
      Screening Questionnaire (MSNQ) to assist in the screening for neuropsychological
      (NP) impairments. Self-report MSNQ scores correlated significantly with measures
      of depression, whereas informant-report MSNQ scores correlated with cognitive
      performance, but not depression. This study was criticized for use of a small
      sample and lack of data regarding normal performance and test-retest reliability.
      The present study was designed to replicate the earlier work with a larger sample
      of patients and normal controls obtained from multiple sites. We also evaluated
      the test-retest reliability and predictive validity of the MSNQ. The sample
      included 85 multiple sclerosis (MS) patients and 40 normal controls, matched on
      demographic variables. All participants completed the MSNQ and underwent NP
      testing. Thirty-four patients were re-examined at one week. Pearson and ANOVA
      techniques were utilized for univariate comparisons. Bayesian statistics were
      calculated to assess predictive validity. Patient self- and informant-report MSNQ
      scores differed from normal and test retest reliability indices were high. Both
      self- and informant-reports were correlated with cognitive dysfunction and
      depression scales. Self-report MSNQ scores correlated more strongly with
      depression than cognitive performance, whereas the opposite pattern was observed
      with informant-report scores. Bayesian statistics showed that informant-report
      MSNQ scores predict cognitive impairment and patient self-report scores identify
      patients with cognitive impairment or depression. It is concluded that the MSNQ
      is useful, although patient self-reports may be exaggerated in depressed patients
      or reduced in patients with severe cognitive impairment.

PMID- 15584494
TI  - Validation of the CNS emotional lability scale for pseudobulbar affect
      (pathological laughing and crying) in multiple sclerosis patients.
AB  - Pseudobulbar affect (PBA) or pathological laughing and crying (PLC) is a disorder
      of affect that occurs in about 10% of multiple sclerosis (MS) patients. The
      objective of this study was to validate the CNS Emotional Lability Scale (CNS-LS)
      in MS patients and to correlate the results with the frequency and intensity of
      episodes of PLC. Physicians at seven private practice referral centers in the
      United States made a diagnosis concerning PLC based on patient interviews.
      Clinical coordinators separately administered the CNS-LS, a self-report measure
      of PLC with seven questions, to MS patients, including patients known to exhibit
      PLC, patients thought to be free of PLC, and newly diagnosed patients where PLC
      status was unknown, and the physician was blinded as to the results. A receiver
      operating characteristic (ROC) curve analysis was performed to define a cut-off
      best correlating with the physician's diagnosis. Of 90 MS patients selected to
      complete the survey, 50 were physician diagnosed with PLC; 40 were without PLC,
      and 15 of these 90 patients were newly diagnosed with MS (<6 months). Scores of
      17 or higher corresponded to a sensitivity of 0.94 and a specificity of 0.83 (LR+
      = 5.5, LR- = 0.07); 89% of patients were correctly diagnosed. The area under the
      ROC curve was 0.95. Symptoms were greater in patients diagnosed as PLC than in
      non-PLC patients as evidenced by mean number of episodes/week, number of
      days/week with episodes, duration of an episode and total time in an episode.
      Similar results were observed if patients were classified as PLC or non-PLC
      according to CNS-LS score > or = 17, suggesting that the CNS-LS is a valid
      measure for the assessment of PLC in MS patients and could be a useful instrument
      for clinical and research purposes.

PMID- 15584495
TI  - Utilization of the auditory consonant trigram test to screen for cognitive
      impairment in patients with multiple sclerosis: comparison with the paced
      auditory serial addition test.
AB  - Several screening methods have been evaluated, but most of them are insensitive
      to MS-related cognitive impairment. The Auditory Consonant Trigram (ACT) test,
      which contains core features required for a working memory task, has been used to
      test neuro-cognitive function in different samples of patients to examine the
      status of working memory. The aim of the present study was to investigate the
      correlation between ACT and the Paced Auditory Serial Addition Test (PASAT), and
      the usefulness of ACT for evaluating the cognitive impairment in MS in a brief
      visit A total of 109 consecutive patients with definite MS were included. The
      patients were administered ACT, PASAT and EDSS. Mean PASAT score and mean ACT
      score were 46.19 +/- 8.51 and 45.30 +/- 9.07, respectively. Correlations between
      EDSS and PASAT, and EDSS and ACT were moderately strong. The correlation between
      ACT and PASAT was very strong (r = 0.831, P < 0.01). The mean time required to
      perform ACT was significantly shorter than PASAT (7.25 +/- 4.72 and 14.70 +/-
      6.97 minutes, respectively). In conclusion, as a relatively brief measure of
      working memory, ACT was well accepted by MS patients and has a strong correlation
      with PASAT. Thus, ACT might be used for rapid evaluation of cognitive impairment
      in patients with multiple sclerosis.

PMID- 15584496
TI  - Quality of life measures for the palliative care of people severely affected by
      multiple sclerosis: a systematic review.
AB  - Although there is increasing interest in measuring the quality of life (QoL) of
      people with multiple sclerosis (MS), relatively little is known about the issues
      of importance to people severely affected by MS. In the first of two systematic
      reviews, we searched the literature to identify measures that have been used to
      assess health-related QoL in people with MS, and described their measurement
      properties in terms of validity, reliability, responsiveness to change, and
      appropriateness for QoL assessment in people severely affected by MS. In the
      second review, we identified care domains important to people with MS, by
      reviewing survey, focus group and interview studies involving people with MS
      and/or their caregivers. Forty-six studies evaluating 12 disease-specific and ten
      generic QoL measures for patients, and one disease-specific measure for
      caregivers, satisfied all inclusion criteria. Sixteen focus group or interview
      studies and 51 questionnaire-based studies evaluated domains of care important to
      people with MS, and seven qualitative and 11 questionnaire-based studies assessed
      domains of care important to their caregivers. From these studies, we identified
      15 domains of care important to people with MS and 12 domains important to
      caregivers. QoL measures differed markedly in their coverage of these care
      domains. Moreover, each measure fulfilled some but not all criteria of validity,
      reliability, responsiveness, and appropriateness. Further work is needed to
      clarify the domains of care relevant to people with severe MS, and to measure
      health-related QoL in this population.

PMID- 15584497
TI  - Alexia without agraphia in multiple sclerosis: case report with magnetic
      resonance imaging localization.
AB  - The syndrome of alexia without agraphia occurs rarely in multiple sclerosis (MS).
      We report a patient with right homonymous hemianopsia and alexia without agraphia
      as his initial manifestations of relapsing-remitting MS. Magnetic resonance
      imaging (MRI) demonstrated a hyperintense lesion in the left occipital
      subcortical white matter (WM) and an enhancing lesion in the splenium of the
      corpus callosum. The clinical presentation and MRI findings were consistent with
      disconnection of the functional right occipital visual cortex from structures
      responsible for language comprehension in the left hemisphere. The diagnosis of
      MS was confirmed by subsequent development of additional periventricular WM
      lesions.

PMID- 15584498
TI  - Improvement of upper limb ataxia and intention tremor allowing cessation of
      thalamic electrostimulation after four years.
AB  - A 34-year-old female patient suffering from multiple sclerosis was treated with
      thalamic electrostimulation for right dominant brachial ataxia and intention
      tremor. At the end of the fourth year, the energy of the battery of the impulse
      generator was depleted. However, the patient was able to use her hands without
      major impairment with the stimulator OFF; due to a stable reduction of the degree
      of ataxia and intention tremor. The opposite thalamus received an electrode that
      was never activated because of a permanent thalamotomy effect. Thus, it can be
      concluded that restoration of function by means of deep brain stimulation might
      have been beneficial towards achieving a reorganization and stabilization of
      subcortico-cortical and cerebellar circuitry, supporting the process of self
      repair in this patient with a less aggressive course of multiple sclerosis.
      However, scientific proof has yet to be found. This exceptional observation
      emphasizes the need for longterm studies.

PMID- 15584499
TI  - Multiple sclerosis and celiac disease: is there an increased risk?
AB  - Multiple sclerosis and celiac disease are both considered immune-mediated
      diseases. Recently, improved serological screening methods provided a higher
      prevalence of celiac disease (CD) in the general population worldwide and also
      demonstrated gastrointestinal symptoms may be lacking. The aim of this study was
      to determine the prevalence of (CD) in an unselected group of 95 adults with
      multiple sclerosis using transglutaminase antibodies. No patients showed
      pathological values. Different immune and genetic basis between the two diseases
      may represent crucial insights to explain our results.

PMID- 15584500
TI  - Longitudinal analyses of the effects of neutralizing antibodies on interferon
      beta-1b in relapsing/remitting multiple sclerosis.

PMID- 15584501
TI  - Divorce and unemployment in multiple sclerosis: recalculation of the data of
      Morales-Gonzales J M, Benito-Leon J, Rivera-Navarro J and Mitchell A J.

PMID- 15584502
TI  - The dependence of the efficiency of gene transfer with the use of lipoplexes
      based on new dicationic lipids on their structure.

PMID- 15584503
TI  - Template-free primer-independent DNA synthesis by bacterial DNA polymerases I
      using the DnaB protein from Escherichia coli.

PMID- 15584504
TI  - Analysis of interaction between the insulator Su(Hw) and the regulatory elements
      of the Abdominal-B gene of Drosophila melanogaster.

PMID- 15584505
TI  - A new strategy for solving the problem of differential detection of natural forms
      of abscisic acid.

PMID- 15584506
TI  - The use of reversible inhibitors of cholinesterases for identification of
      intraspecific groups of the Comandor squid Berryteuthis magister from different
      zones of the northwestern area of the Pacific Ocean.

PMID- 15584507
TI  - Analysis of the effect of the Su(Hw) insulator on the expression of the miniwhite
      gene in Drosophila melanogaster.

PMID- 15584508
TI  - Fluorinated derivatives of benz[4,5]imidazo[1,2-b][1,3] thiazole--inhibitors of
      reproduction of measles virus.

PMID- 15584509
TI  - Polyamines suppress expression of the cytokinin-dependent transgene in
      Arabidopsis.

PMID- 15584510
TI  - The functional motifs that are revealed in the gypsy Gag amino acid sequence.

PMID- 15584511
TI  - The Qy band of bacteriochlorophyll as an indicator of interactions between
      structural functional elements of the purple bacterium Blastochloris viridis.

PMID- 15584512
TI  - Study of the properties of two homologues of yeast ADA2 in Drosophila
      melanogaster.

PMID- 15584513
TI  - Revealing of somatic mosaicism in adult mice by DNA fingerprinting.

PMID- 15584514
TI  - Aminoalkylphosphinates are new effective inhibitors of melanogenesis and
      fungicides.

PMID- 15584515
TI  - Characteristic of the silencer located in the CpG-rich region upstream of the
      cluster of chicken alpha-globin genes.

PMID- 15584516
TI  - Expression of the retrovirus gypsy Gag in Spodoptera frugiperda cell culture with
      the recombinant baculovirus.

PMID- 15584517
TI  - Study of the genetic variability of Crimean-Congo hemorrhagic fever virus in
      Central Asia.

PMID- 15584518
TI  - Phylogenetic comparison of the genomes of different strains of variola virus.

PMID- 15584519
TI  - Allantoin as a vitamin.

PMID- 15584520
TI  - Conversion of allergic reaction into immune response by allergotropins.

PMID- 15584521
TI  - Quantitative methods of analysis of footprinting diagrams for the complexes
      formed by a ligand and a DNA fragment of known sequence.

PMID- 15584522
TI  - Effect of redox agents on hydrolytic activity of H+ Atpase in plant vacuolar
      membrane.

PMID- 15584523
TI  - Photobleaching kinetics of Photofrin in vivo and in multicell tumour spheroids
      indicate two simultaneous bleaching mechanisms.
AB  - We present a detailed investigation of Photofrin photobleaching and photoproduct
      accumulation. Fisher rats were sensitized with 10 mg kg(-1) Photofrin and
      irradiated 24 h later with 514 nm light at 5 or 100 mW cm(-2). Fluorescence
      spectra were collected from the skin throughout treatment, and sensitizer
      bleaching and fluorescent photoproduct formation were quantified using spectral
      analysis. Photofrin bleaching was slightly more rapid at the higher irradiance
      under these conditions. However, accumulation of photoproduct was significantly
      enhanced at lower irradiance. To interpret these unexpected findings, we
      developed a new mathematical model in which reactions between singlet oxygen
      (1O2) and the photosensitizer and reactions between the sensitizer triplet and
      biological targets are both allowed to contribute to bleaching. Predictions of
      this model were tested in experiments performed on EMT6 spheroids sensitized with
      concentrations of 2.5, 10 and 30 microg mL(-1) Photofrin and subjected to PDT.
      Photofrin bleaching and photoproduct formation in these spheroids were measured
      using confocal fluorescence spectroscopy. In qualitative agreement with the mixed
      mechanism model predictions, at the highest drug concentration Photofrin
      bleaching was more efficient via 1O2 reactions, while at the lowest concentration
      triplet reactions were more efficient. At all concentrations, photoproduct
      accumulation was greater under conditions of abundant oxygen.

PMID- 15584524
TI  - Comparison of human skin opto-thermal response to near-infrared and visible laser
      irradiations: a theoretical investigation.
AB  - Near-infrared wavelengths are absorbed less by epidermal melanin, and penetrate
      deeper into human skin dermis and blood than visible wavelengths. Therefore,
      laser irradiation using near-infrared wavelengths may improve the therapeutic
      outcome of cutaneous hyper-vascular malformations in moderately to heavily
      pigmented skin patients and those with large-sized blood vessels or blood vessels
      extending deeply into the skin. A mathematical model composed of a Monte Carlo
      algorithm to estimate the distribution of absorbed light, numerical solution of a
      bio-heat diffusion equation to calculate the transient temperature distribution,
      and a damage integral based on an empirical Arrhenius relationship to quantify
      the tissue damage was utilized to investigate the optothermal response of human
      skin to near-infrared and visible laser irradiations in conjunction with cryogen
      spray cooling. In addition, the thermal effects of a single continuous laser
      pulse and micropulse-composed laser pulse profiles were compared. Simulation
      results indicated that a 940 nm wavelength induces improved therapeutic outcome
      compared with a 585 and 595 nm wavelengths for the treatment of patients with
      large-sized blood vessels and moderately to heavily pigmented skin. On the other
      hand, a 585 nm wavelength shows the best efficacy in treating small-sized blood
      vessels, as characterized by the largest laser-induced blood vessel damage depth
      compared with 595 and 940 nm wavelengths. Dermal blood content has a considerable
      effect on the threshold incident dosage for epidermal damage, while the effect of
      blood vessel size is minimal. For the same macropulse duration and incident
      dosage, a micropulse-composed pulse profile results in higher peak temperature at
      the basal layer of skin epidermis than an ideal single continuous pulse profile.

PMID- 15584525
TI  - Monte carlo simulation of the Leksell Gamma Knife: II. Effects of heterogeneous
      versus homogeneous media for stereotactic radiosurgery.
AB  - The absence of electronic equilibrium in the vicinity of bone-tissue or air
      tissue heterogeneity in the head can misrepresent deposited dose with treatment
      planning algorithms that assume all treatment volume as homogeneous media. In
      this paper, Monte Carlo simulation (PENELOPE) and measurements with a specially
      designed heterogeneous phantom were applied to investigate the effect of air
      tissue and bone-tissue heterogeneity on dose perturbation with the Leksell Gamma
      Knife. The dose fall-off near the air-tissue interface caused by secondary
      electron disequilibrium leads to overestimation of dose by the vendor supplied
      treatment planning software (GammaPlan) at up to 4 mm from an interface. The dose
      delivered to the target area away from an air-tissue interface may be
      underestimated by up to 7% by GammaPlan due to overestimation of attenuation of
      photon beams passing through air cavities. While the underdosing near the air
      tissue interface cannot be eliminated with any plug pattern, the overdosage due
      to under-attenuation of the photon beams in air cavities can be eliminated by
      plugging the sources whose beams intersect the air cavity. Little perturbation
      was observed next to bone-tissue interfaces. Monte Carlo results were confirmed
      by measurements. This study shows that the employed Monte Carlo treatment
      planning is more accurate for precise dosimetry of stereotactic radiosurgery with
      the Leksell Gamma Knife for targets in the vicinity of air-filled cavities.

PMID- 15584526
TI  - Monte carlo simulation of x-ray spectra in diagnostic radiology and mammography
      using MCNP4C.
AB  - The general purpose Monte Carlo N-particle radiation transport computer code
      (MCNP4C) was used for the simulation of x-ray spectra in diagnostic radiology and
      mammography. The electrons were transported until they slow down and stop in the
      target. Both bremsstrahlung and characteristic x-ray production were considered
      in this work. We focus on the simulation of various target/filter combinations to
      investigate the effect of tube voltage, target material and filter thickness on x
      ray spectra in the diagnostic radiology and mammography energy ranges. The
      simulated x-ray spectra were compared with experimental measurements and spectra
      calculated by IPEM report number 78. In addition, the anode heel effect and off
      axis x-ray spectra were assessed for different anode angles and target materials
      and the results were compared with EGS4-based Monte Carlo simulations and
      measured data. Quantitative evaluation of the differences between our Monte Carlo
      simulated and comparison spectra was performed using student's t-test statistical
      analysis. Generally, there is a good agreement between the simulated x-ray and
      comparison spectra, although there are systematic differences between the
      simulated and reference spectra especially in the K-characteristic x-rays
      intensity. Nevertheless, no statistically significant differences have been
      observed between IPEM spectra and the simulated spectra. It has been shown that
      the difference between MCNP simulated spectra and IPEM spectra in the low energy
      range is the result of the overestimation of characteristic photons following the
      normalization procedure. The transmission curves produced by MCNP4C have good
      agreement with the IPEM report especially for tube voltages of 50 kV and 80 kV.
      The systematic discrepancy for higher tube voltages is the result of systematic
      differences between the corresponding spectra.

PMID- 15584527
TI  - The effect of optimization on surface dose in intensity modulated radiotherapy
      (IMRT).
AB  - Although IMRT has been shown clinically to increase skin doses for some patients,
      it has also been shown that intensity modulated delivery does not, of itself,
      increase skin doses. The reason for this apparent difference is that inverse
      planning can result in solutions that give high fluence to tangential beam
      segments near the skin surface, in an attempt to counter the build-up region. In
      cases where the clinical target volume (CTV) stops short of the skin surface, but
      the planning target volume (PTV) does not, there is no clinical reason to treat
      the skin. The CTV-PTV margin exists purely to ensure that fields are large enough
      to allow for geometrical uncertainties. With an objective function based on the
      doses to the PTV, it is possible for a plan that gives excess fluence to the skin
      to have a lower objective function, and hence to be preferred in an optimization.
      We describe a technique of plan evaluation, based on analysis of a plan by
      recalculating several plans in which the isocentre has been offset by a distance
      equal to the CTV-PTV margin. We demonstrate that changes to a plan that reduce a
      PTV-based objective can give a worse dose distribution to the CTV when systematic
      and random set-up errors are accounted for, and increase skin dose. Several
      possible strategies for avoiding this problem are discussed, including the use of
      the skin as an organ at risk, modification of the PTV to avoid the skin, and the
      use of 'pretend bolus' applied in planning but not in treatment. The latter gave
      the best results. The possibility of using the evaluation method itself, as the
      basis of an objective function for optimization, is discussed.

PMID- 15584528
TI  - Commissioning of a medical accelerator photon beam Monte Carlo simulation using
      wide-field profiles.
AB  - A method for commissioning an EGSnrc Monte Carlo simulation of medical linac
      photon beams through wide-field lateral profiles at moderate depth in a water
      phantom is presented. Although depth-dose profiles are commonly used for nominal
      energy determination, our study shows that they are quite insensitive to energy
      changes below 0.3 MeV (0.6 MeV) for a 6 MV (15 MV) photon beam. Also, the depth
      dose profile dependence on beam radius adds an additional uncertainty in their
      use for tuning nominal energy. Simulated 40 cm x 40 cm lateral profiles at 5 cm
      depth in a water phantom show greater sensitivity to both nominal energy and
      radius. Beam parameters could be determined by comparing only these curves with
      measured data.

PMID- 15584529
TI  - Prostate segmentation algorithm using dyadic wavelet transform and discrete
      dynamic contour.
AB  - Knowing the location and the volume of the prostate is important for ultrasound
      guided prostate brachytherapy, a commonly used prostate cancer treatment method.
      The prostate boundary must be segmented before a dose plan can be obtained.
      However, manual segmentation is arduous and time consuming. This paper introduces
      a semi-automatic segmentation algorithm based on the dyadic wavelet transform
      (DWT) and the discrete dynamic contour (DDC). A spline interpolation method is
      used to determine the initial contour based on four user-defined initial points.
      The DDC model then refines the initial contour based on the approximate
      coefficients and the wavelet coefficients generated using the DWT. The DDC model
      is executed under two settings. The coefficients used in these two settings are
      derived using smoothing functions with different sizes. A selection rule is used
      to choose the best contour based on the contours produced in these two settings.
      The accuracy of the final contour produced by the proposed algorithm is evaluated
      by comparing it with the manual contour outlined by an expert observer. A total
      of 114 2D TRUS images taken for six different patients scheduled for
      brachytherapy were segmented using the proposed algorithm. The average difference
      between the contour segmented using the proposed algorithm and the manually
      outlined contour is less than 3 pixels.

PMID- 15584530
TI  - Performance improvement of small gamma camera using NaI(Tl) plate and position
      sensitive photo-multiplier tubes.
AB  - The purpose of this study was to improve the performance of a small gamma camera,
      utilizing a NaI(Tl) plate and a 5" position sensitive PMT. We attempted to build
      a NaI(Tl) plate crystal system which retained all its advantages, while at the
      same time integrating some of the advantages inherent in an array-type
      scintillation crystal system. Flood images were obtained with a lead hole mask,
      and position mapping was performed by detecting hole positions in the flood
      image. Energy calibration was performed using the energy spectra obtained from
      each hole position. Flood correction was performed using a uniformity correction
      table containing the relative efficiency of each image element. The spatial
      resolution was improved about 16% after correction at the centre field of view.
      Resolution deterioration at the outer field of view (OFOV) was considerably
      ameliorated, from 6.7 mm to 3.2 mm after correction. The sensitivity at the OFOV
      was also increased after correction, from 0.7 cps microCi(-1) to 2.0 cps microCi(
      1). The correction also improved uniformity, from 5.2% to 2.1%, and linearity,
      from 0.5 mm to 0 mm. The results of this study indicate that the revised
      correction method can be employed to considerably improve the performance of a
      small gamma camera using a NaI(Tl) plate-type crystal. This method also provides
      high spatial resolution and linearity, like array-type crystals do, while
      retaining the specific advantages of plate-type crystals.

PMID- 15584531
TI  - S-values calculated from a tomographic head/brain model for brain imaging.
AB  - A tomographic head/brain model was developed from the Visible Human images and
      used to calculate S-values for brain imaging procedures. This model contains 15
      segmented sub-regions including caudate nucleus, cerebellum, cerebral cortex,
      cerebral white matter, corpus callosum, eyes, lateral ventricles, lenses,
      lentiform nucleus, optic chiasma, optic nerve, pons and middle cerebellar
      peduncle, skull CSF, thalamus and thyroid. S-values for C-11, O-15, F-18, Tc-99m
      and I-123 have been calculated using this model and a Monte Carlo code, EGS4.
      Comparison of the calculated S-values with those calculated from the MIRD (1999)
      stylized head/brain model shows significant differences. In many cases, the
      stylized head/brain model resulted in smaller S-values (as much as 88%),
      suggesting that the doses to a specific patient similar to the Visible Man could
      have been underestimated using the existing clinical dosimetry.

PMID- 15584532
TI  - Acoustically modulated x-ray phase contrast imaging.
AB  - We report the use of ultrasonic radiation pressure with phase contrast x-ray
      imaging to give an image proportional to the space derivative of a conventional
      phase contrast image in the direction of propagation of an ultrasonic beam.
      Intense ultrasound is used to exert forces on objects within a body giving
      displacements of the order of tens to hundreds of microns. Subtraction of images
      made with and without the ultrasound field gives an image that removes low
      spatial frequency features and highlights high frequency features. The method
      acts as an acoustic 'contrast agent' for phase contrast x-ray imaging, which in
      soft tissue acts to highlight small density changes.

PMID- 15584533
TI  - Mammographic image restoration using maximum entropy deconvolution.
AB  - An image restoration approach based on a Bayesian maximum entropy method (MEM)
      has been applied to a radiological image deconvolution problem, that of reduction
      of geometric blurring in magnification mammography. The aim of the work is to
      demonstrate an improvement in image spatial resolution in realistic noisy
      radiological images with no associated penalty in terms of reduction in the
      signal-to-noise ratio perceived by the observer. Images of the TORMAM
      mammographic image quality phantom were recorded using the standard magnification
      settings of 1.8 magnification/fine focus and also at 1.8 magnification/broad
      focus and 3.0 magnification/fine focus; the latter two arrangements would
      normally give rise to unacceptable geometric blurring. Measured point-spread
      functions were used in conjunction with the MEM image processing to de-blur these
      images. The results are presented as comparative images of phantom test features
      and as observer scores for the raw and processed images. Visualization of high
      resolution features and the total image scores for the test phantom were improved
      by the application of the MEM processing. It is argued that this successful
      demonstration of image de-blurring in noisy radiological images offers the
      possibility of weakening the link between focal spot size and geometric blurring
      in radiology, thus opening up new approaches to system optimization.

PMID- 15584534
TI  - An advanced boundary element method (BEM) implementation for the forward problem
      of electromagnetic source imaging.
AB  - The forward problem of electromagnetic source imaging has two components: a
      numerical model to solve the related integral equations and a model of the head
      geometry. This study is on the boundary element method (BEM) implementation for
      numerical solutions and realistic head modelling. The use of second-order
      (quadratic) isoparametric elements and the recursive integration technique
      increase the accuracy in the solutions. Two new formulations are developed for
      the calculation of the transfer matrices to obtain the potential and magnetic
      field patterns using realistic head models. The formulations incorporate the use
      of the isolated problem approach for increased accuracy in solutions. If a
      personal computer is used for computations, each transfer matrix is calculated in
      2.2 h. After this pre-computation period, solutions for arbitrary source
      configurations can be obtained in milliseconds for a realistic head model. A
      hybrid algorithm that uses snakes, morphological operations, region growing and
      thresholding is used for segmentation. The scalp, skull, grey matter, white
      matter and eyes are segmented from the multimodal magnetic resonance images and
      meshes for the corresponding surfaces are created. A mesh generation algorithm is
      developed for modelling the intersecting tissue compartments, such as eyes. To
      obtain more accurate results quadratic elements are used in the realistic meshes.
      The resultant BEM implementation provides more accurate forward problem solutions
      and more efficient calculations. Thus it can be the firm basis of the future
      inverse problem solutions.

PMID- 15584535
TI  - Materials for phantoms for terahertz pulsed imaging.
AB  - Phantoms are commonly used in medical imaging for quality assurance, calibration,
      research and teaching. They may include test patterns or simulations of organs,
      but in either case a tissue substitute medium is an important component of the
      phantom. The aim of this work was to identify materials suitable for use as
      tissue substitutes for the relatively new medical imaging modality terahertz
      pulsed imaging. Samples of different concentrations of the candidate materials
      TX151 and napthol green dye were prepared, and measurements made of the frequency
      dependent absorption coefficient (0.5 to 1.5 THz) and refractive index (0.5 to
      1.0 THz). These results were compared qualitatively with measurements made in a
      similar way on samples of excised human tissue (skin, adipose tissue and striated
      muscle). Both materials would be suitable for phantoms where the dominant
      mechanism to be simulated is absorption (approximately 100 cm(-1) at 1 THz) and
      where simulation of the strength of reflections from boundaries is not important;
      for example, test patterns for spatial resolution measurements. Only TX151 had a
      frequency-dependent refractive index close to that of tissue, and could therefore
      be used to simulate the layered structure of skin, the complexity of
      microvasculature or to investigate frequency-dependent interference effects that
      have been noted in terahertz images.

PMID- 15584536
TI  - Experimental energy response verification of XR type T radiochromic film.
AB  - This short note investigates the energy response characteristics of a relatively
      new high sensitivity radiochromic film (XR type T) and compares it to other
      radiochromic and radiographic films and thermoluminescent dosimeters. Results
      show that the energy response of the new XR type T film is relatively large over
      the range of therapeutic energies from 50 kVp superficial x-ray treatment to 18
      MV high energy radiotherapy treatment. When normalized to 1 at a standard 6 MV
      radiotherapy x-ray energy the XR type T film produced a normalized dose response
      of approximately 6 in the energy range of 30 keV to 70 keV thus representing an
      increase in sensitivity at lower energies similar to that observed for
      radiographic x-ray films. This is quite different from previous versions of
      Gafchromic film where the energy response of the film decreases at lower energies
      down to levels approximately 0.6-0.7 for the same effective energies. This type
      of film has been optimized for use in diagnostic energy ranges producing a
      relatively uniform dose response in the 30 keV to 70 keV range.

PMID- 15584537
TI  - [Morbid obesity: a risk factor for obstetric complications].
AB  - In a primipara, 28 years of age and with a BMI of 44 kg/m2, a Zavanelli manoeuvre
      was performed. Due to uterine atony she had to undergo a hysterectomy. A
      multipara, 39 years of age and with a BMI of 66 kg/m2, experienced that her
      weight exceeded the limits of the beds and that local anaesthesia was hard to
      perform; she suffered from a lesion of the lumbosacral plexus caused by a
      shoulder dystocia. In the end, both mothers and their babies could go home in a
      moderate condition. Obesity is becoming more prevalent and brings with it an
      increase in obstetric risks. During pregnancy and delivery, morbidly obese
      patients should be monitored by a gynaecologist. Special interest should focus on
      screening for (gestational) diabetes, hypertension and foetal growth. Ultrasound
      may detect congenital malformations early; however, the sensitivity of ultrasound
      is lower in morbidly obese patients. When macrosomia is expected, a clear plan
      should be made regarding the mode of delivery. It is useful to make a treatment
      protocol for morbidly obese patients.

PMID- 15584538
TI  - [Liver transplantation from a living donor].
AB  - Recently the first three liver transplantations from living donors were performed
      in The Netherlands. The motivations to proceed with this new procedure were
      threefold; the existing shortage of post-mortem organ donors, the successful
      transplants reported in the literature and the supposedly better organ quality
      and favourable-logistics of the procedure. This new procedure is in line with a
      recent advisory report on organ donation from the National Health Council of The
      Netherlands. As long as there is a shortage of post-mortem donors, living
      donation is a necessary treatment for patients with otherwise fatal liver
      insufficiency. However this should not keep public and governmental organisations
      from its continuing efforts to promote post-mortem donation. These should also
      include a discussion regarding changes to the organ donation law.

PMID- 15584539
TI  - [Skeletal maturation in assessing underage asylum seekers].
AB  - Single underage asylum seekers are granted a residence permit faster and more
      easily than their grown-up counterparts. Since the large majority of those
      applying for such a permit do not have any identification papers, objective
      assessment is necessary but often absent. Skeletal maturation as seen on an X-ray
      of the hand or the medial clavicle gives some indication of age, but cannot
      determine precisely whether the applicant is below or above 18 years of age.
      Furthermore, few studies have looked at the accuracy and reproducibility of these
      radiographic investigations, so their interpretation is mainly based on expert
      opinion. Doubt about the usefulness of the assessment of the medial clavicle is
      the subject of the article by Van Rijn and Robben in this journal. This
      discussion deals with some aspects of their study including the description of
      the study population, the quality of the interobserver study and the theoretical
      arguments against the use of the method. More observational data should be
      collected. To date however, the use of the medial clavicular X-ray has not been
      shown to be invalid.

PMID- 15584540
TI  - [Diagnosis of pigmented skin lesions: how to recognize a malignant melanoma].
AB  - An accurate answer to the clinical question of whether a pigmented skin lesion
      has become a malignant melanoma or not is difficult because of the clinical
      variability of this lesion. Because of the low incidence of 2400 new melanoma
      cases each year in The Netherlands, a general practitioner only sees one new case
      every 3-4 years. The best way to distinguish between a benign lesion and a
      malignant melanoma is the combined use of several criteria, such as in the ABCD
      formula: asymmetry, border irregularity, colour variation and a diameter > 6 mm.
      Dermatoscopical examination, provided that the technique is used by well-trained
      and experienced physicians, is a valuable adjunct to clinical examination. A
      pigmented lesion should always be excised if there is not enough convincing
      evidence to exclude its malignant nature. Histological classification of
      pigmented lesions may prove difficult because of morphological overlap between
      benign and malignant melanocytic tumours.

PMID- 15584541
TI  - [Risk factors for skin melanoma: genetic factors probably more important than
      exposure to sunlight].
AB  - Pigmented naevi (moles) are increasingly regarded as risk factors for the
      development of melanoma. The probability of melanoma developing from congenital
      naevi is proportional to the volume of the naevi. The risk of melanoma
      development from large naevi (diameter > 20 cm) is already present in the early
      years of childhood. The most important risk factor is the higher number of
      acquired naevi. This applies particularly to dysplastic (also called clinically
      atypical) naevi that not only represent the highest risk group but are also
      considered potential melanoma precursors. The development of acquired naevi
      (including dysplastic naevi) is dependant on the degree of skin pigmentation. The
      role of sunlight (ultraviolet radiation) in the development of melanoma is less
      significant than is generally assumed. The indirect effect of sunlight on
      melanoma development is to stimulate naevogenesis. One of the risk-modifying
      genes is the gene coding for melanocortin-1-receptor (MC1R). The presence of some
      gene variants has been found to lead to changes in melanin synthesis and is
      associated with a higher risk of melanoma. Recent research has shown that
      dysplastic naevi synthesise more phaeomelanin. There are also strong indications
      that dysplastic naevus cells suffer from chronic oxidative stress. This situation
      can lead to hypermutability and genetical instability.

PMID- 15584542
TI  - [Diagnostic image (215). A woman with abdominal pain and hepatosplenomegaly].
AB  - A 30-year-old woman presented with abdominal pain, cholelithiasis and
      hepatosplenomegaly, due to Gaucher's disease.

PMID- 15584543
TI  - [Radiography of the medial ends of the clavicles by the method of the Dutch
      Immigration and Naturalisation Service is unsuitable for determining adulthood].
AB  - OBJECTIVE: A critical examination of the radiological technique used by the Dutch
      Immigration and Naturalisation Service (IND) for determining the adulthood of
      persons around the age of 18. DESIGN: Descriptive. METHOD: Radiographs of the
      hands and clavicles were reassessed in 29 asylum seekers (15 boys, 9 girls and 5
      persons of unknown gender) in whom the IND suspected a discrepancy between the
      true age and the age stated. In each case, 1 hand radiograph and 3 clavicular
      views were taken: 1 posteroanterior standard view as well as 2 oblique views, in
      order to assess the epiphyses at the medial ends of the clavicles. Additionally,
      the radiographs of one of these subjects were shown to 241 radiologists and
      radiologists-in-training. RESULTS: On all the hand X-rays, the epiphyses were
      closed. Based on this, the skeletal age of the girls was at least 15 years and 11
      months and that of the boys at least 17 years and 3 months. The medial ends of
      the clavicles could not be assessed on the standard views due to overprojection
      of the spinal column. In 55 of the 58 films in which the thorax was turned, the
      direction of the X-rays was not appropriate for assessing the growth plates. The
      other 3 could not be assessed as there were no existing objective radiological
      criteria. The assessments of the stage of development as an indication of
      skeletal age in the cases presented differed greatly from one another.
      CONCLUSION: The radiographs that were taken to establish whether or not the
      asylum seekers were underage were unsuitable for the purpose for which they were
      taken.

PMID- 15584544
TI  - [Problematic care for a trauma patient with morbid obesity].
AB  - A 33-year-old woman was trapped in a car following an accident. Because of her
      size (241 kg; BMI: 85 kg/m2) it was difficult to free, transport, examine and
      treat her. A few days after she had been discharged with a knee injury, she was
      again admitted for pneumonia. Partly as a result of para-infectious
      rhabdomyolysis, she died 5 days later. More and more people in The Netherlands
      are overweight, and more and more often to an extreme degree. Complicated
      accident kinetics, problems with diagnosis and treatment, comorbidity and an
      increased risk of complications in obese patients contribute to the poorer
      prognosis following blunt trauma. It is therefore practically impossible to give
      obese patients the usual care according to the protocol. Adaptations like
      positioning in the anti-Trendelenburg, left lateral-tilt position, as well as
      bigger and stronger equipment, may improve the care of trauma patients with
      morbid obesity.

PMID- 15584545
TI  - [The practice guideline 'Stable angina pectoris' (second revision) from the Dutch
      College of General Practitioners; a response from the perspective of cardiology].

PMID- 15584546
TI  - [Increased tumor growth of non-small-cell lung tumor in the waiting time between
      induction chemotherapy and longterm radiotherapy].

PMID- 15584547
TI  - A love-hate affair: what health service managers really think.

PMID- 15584548
TI  - Prison healthcare. Inside story.

PMID- 15584549
TI  - Hilary Thomas on clinical management.

PMID- 15584550
TI  - Ochratoxin A-induced apoptosis in rat kidney tissue.
AB  - The aim of our study was to find whether ochratoxin A (OTA) induces the apoptosis
      and/or necrosis of kidney tissue in rats. In the first experiment, the highest
      number of apoptotic cells was found in rats sacrificed one day after OTA
      administration (1.00 mg/kg b.w., i.p.). The number of apoptotic cells reduced
      gradually and they were not seen nine days after OTA administration. A possible
      dose-dependence of histological changes was checked in kidney tissue of rats
      given 0.25, 0.50 or 1.00 mg of OTA/kg b.w., i.p. three times a week for four
      weeks. The number of apoptotic cells showed a clear dose-dependence, but necrosis
      was absent even at the highest doses. The time-dependent appearance of lesions
      related to OTA administration was checked by administering 0.50 mg OTA/kg body
      weight to rats, and sacrificing them one day after 1, 3, 6, and 9
      doses/administrations, or 6 and 21 day after 12 doses/administrations. Long-term
      administration is associated with continued and increased apoptosis without
      necrosis, suggestive of OTA's role in the pathogenesis of progressive renal
      atrophy.

PMID- 15584551
TI  - Evaluation of in vitro genotoxic activity of bleomycin and mitomycin C in human
      lymphocytes using the alkaline comet assay.
AB  - Although chemotherapy targets cancer tissue, it also damages the DNA of non
      cancer cells. The aim of this study was to evaluate the in vitro genotoxic
      potential of therapeutic concentrations of bleomycin and mitomycin C, added alone
      or in combination to cultures of human peripheral lymphocytes. The levels of DNA
      damage and repair were assessed using the alkaline comet assay immediately after
      cell treatment as well as 24 and 48 hours following treatment. The results
      indicate that individual drugs and their combination induce a significant DNA
      damage to peripheral blood lymphocytes. Bleomycin alone induced the highest
      levels of primary DNA damage immediately after cell treatment. Although mitomycin
      C alone induced massive cross-linking and retarded DNA migration in resting
      cells, active proliferation and repair processes significantly increased DNA
      damage. Combined, they showed a synergetic effect, inducing complex patterns of
      DNA damage in peripheral blood lymphocytes and producing different types of
      lesions and a number of DNA alterations that directly or indirectly increased DNA
      migration. Our study has confirmed the sensitivity of the alkaline comet assay
      for assessing bleomycin and/or mitomycin C genotoxicity to human lymphocytes at
      concentration levels used in clinic. It has also demonstrated the utility of the
      alkaline comet assay as one of the primary screening methods for in vitro studies
      of drug-DNA interactions, especially in studying mechanisms of action of new
      drugs.

PMID- 15584552
TI  - Occupational accidents and injuries: results of a safety preventive programme.
AB  - The purpose of this study was to establish and compare the number and the average
      annual rate of occupational accidents and traumatic injuries in two industrial
      plants (textile production, and manufacture of metal products) between 1993 and
      2002 and to estimate the effects of a safety programme introduced in textile
      industry. Textile industry plant has been implementing a programme for the
      surveillance and prevention of occupational accidents and injuries since 1997.
      From 1998 to 2002, the average annual rates of accidents and injuries rates and
      the severity ratio of injuries in this plant dropped significantly, which was not
      the case with metal production plant. The safety training programme produced the
      best results with the youngest and the oldest workers with less than five years
      of job experience.

PMID- 15584553
TI  - Results of clinical-toxicological assessments performed in the Poison Control
      Centre in Zagreb over a 10-year period.
AB  - The aim of this study was to see which harmful substances and which occupational
      settings most often required toxicological assessment, to evaluate exposure data
      provided by employers and to see to what extent could this assessment rely on
      actual measurements of harmful substances in a working environment. We reviewed
      the documentation that was submitted for toxicological assessment in all patients
      referred from occupational health physicians between 1992 and 2001. From 1992 to
      2001, the Poison Control Centre performed a total of 260 toxicological
      evaluations of occupational exposure to harmful chemicals. In 162 cases (62%),
      measurements of harmful substance concentrations in the working environment would
      have been of primary significance for the best comparison of potential adverse
      effects and the level of exposure. The most frequent was exposure to organic
      solvents in the production line and the use of various paints and varnishes,
      adhesives and thinners in shoe, chemical and metal-processing industry. Follows
      exposure to respiratory irritants, mostly in plastic and metal processing.
      However, measurement data of harmful substances in the working environment were
      available only in 24 cases, that is, in 9% of all documents submitted for
      toxicological assessment. Exposure to organic solvents is characteristic for a
      large number of work places in industry and small enterprises in Croatia, and it
      is necessary to carry out a more comprehensive study about the real levels of
      exposure and modes of effective control. It is important because the EU
      regulations on the indicative occupational exposure limits (OELs) of harmful
      substances in the working environment, that will soon be implemented into
      Croatian legislation, recommend a reduction of maximum allowable concentrations
      (MAC) for commonly used solvents.

PMID- 15584554
TI  - Implementation of bioavailability in standard setting and risk assessment:
      suggestions based on a workshop with emphasis on metals.
AB  - Bioavailability is increasingly recognised as the key issue linking increased
      levels of toxicants with actually occurring adverse effects in ecosystems, whilst
      taking the modifying effects of the abiotic components of the environment into
      account. Various factors may affect bioavailability in the field, and often these
      factors are time- and space-dependent. This is one of the main reasons why
      legislators have been reluctant in implementing bioavailability in risk
      assessment procedures. Over the last few years, however, considerable scientific
      progress has been made with regard to better understanding of chemical and
      ecological mechanisms responsible for rendering chemicals available for uptake
      and toxicity. As a consequence, legislators face the challenge to anticipate the
      scientific progress and to implement bioavailability in legislation. This paper
      discusses the possibilities of implementing various methodologies within a
      maximum period of time of three years.

PMID- 15584555
TI  - [Antioxidative and antiradical activity of flavonoids].
AB  - Flavonoids are a major group of phenolic compounds which are important in
      flavouring and colouring of many fruits and vegetables and derived products such
      as wine, tea preparations and chocolate. Recently, flavonoids are given much
      attention due to their excellent antioxidative and antiradical activity. Studies
      have revealed that flavonoids are good scavengers of free radicals, and
      consequently, they are much used in pharmaceutical and food industries.
      Flavonoids also have a gamut of other biochemical activities; some have been
      found to possess significant anti-cardiovascular disease, anti-inflammatory, anti
      allergic, anti-mutagenic, antiviral, anti-tumour and activities.

PMID- 15584556
TI  - [General population exposure to volatile aromatic hydrocarbons].
AB  - Aromatic hydrocarbons benzene, toluene, ethylbenzene, and isomeric xylenes (BTEX)
      are volatile organic compounds widespread in the biosphere because of their
      physical and chemical properties and their use. They are major constituents of
      gasoline, and vehicular traffic is the main source of BTEX in the environment.
      Significant additional exposure to BTEX results from tobacco smoking. General
      population is more or less permanently exposed to BTEX. This review summarises
      their distribution in the environment, analytical methods for BTEX determination
      in biological samples, and published data on BTEX concentrations in blood,
      exhaled air and urine samples of general population. The paper also describes
      toxic effects of BTEX on human health associated exclusively with professional
      exposure. Concentrations of these compounds in biological samples collected from
      general population reflect environmental pollution. Biological monitoring of
      people exposed to environmental BTEX concentrations is the first step toward
      evaluating health risk.

PMID- 15584557
TI  - [Genetically modified organisms in food--production, detection and risks].
AB  - The first genetically modified plant (GMP) was a tobacco resistant to antibiotics
      in 1983. In 1996, the first genetically altered crop, a delayed-ripening tomato
      was commercially released. In the year 2003, the estimated global area of GM
      crops for was 67.7 million hectares. To produce such a plant a gene of interest
      has to be isolated from the donor. Together with a promoter, terminator sequence
      and marker gene it has to be introduced into the plant cell which is then
      stimulated to generate a whole GMP expressing new characteristics
      (herbicide/insect resistance, delayed ripening). The last few months have seen a
      strong public debate over genetically modified organisms which has raised
      scientific, economic, political, and ethical issues. Some questions concerning
      the safety of GMPs are still to be answered, and decisions about their future
      should be based on scientifically validated information.

PMID- 15584558
TI  - [Chemistry and biological effects of gliotoxin].
AB  - Gliotoxin is a mycotoxin from the epipolythiodioxypipeazine family with
      biological active internal disulfide bridge. Gliotoxin has an antibacterial and
      antiviral activity, but it was discarded from clinical practice due to its
      toxicity. The most studied effect of gliotoxin is its influence on the cell of
      the immune system. Today, researches are focused on treating transplantation
      organs ex situ and making them immunologically silent. Its toxicity has been
      proven on several cells (macrophages, thymocites, splenocytes, and fibroblasts)
      causing apoptosis and necrosis and it has acted as inhibitor of several enzymes
      (farnesyl-transefases, NF-kappaB, and alcohol-dehydrogenases). Its mechanism of
      toxicity is connected with the production of mixed disulfide and covalent bonds,
      and oxidative effects. An important medical mould Aspergillus fumigatus and yeast
      Candida albicans can secrete gliotoxin in infected tissues and, because of the
      proven toxic effects of gliotoxin, it is suggested that gliotoxin can exacerbate
      mycoses (invasive aspergillosis or candidiasis). Gliotoxin can also affect the
      invasiveness of fungi and their dissemination from the primary site throughout
      the organism.

PMID- 15584559
TI  - [Impact of radiofrequency/microwave radiation on cell and cytoskeleton
      structure].
AB  - The increasing number of mobile phone users raises concern about possible
      hazardous effects of radiofrequency/microwave (RF/MW) electromagnetic fields. The
      most intriguing issue is the existence of the so called non-thermal effect which
      is not related to increased temperature. Possible biological effects, associated
      with the exposure to RF/MW fields have not been elucidated so far. A number of in
      vitro studies have attempted to see whether permissible levels of RF/MW affect
      the cell membrane, gene transcription, apoptosis, and whether they induce stress.
      However, the effect of RF/MW on the cytoskeleton, one of the most important cell
      structures, remains unknown. Cytoskeleton is a functional and structural part of
      the cell, composed of actin, intermedial filaments and microtubules. Microtubules
      direct the distribution of cellular organelles, determine cell shape, cell
      polarity and segregation of chromosomes during mitosis.

PMID- 15584560
TI  - Cardiac amyloidosis--an update.

PMID- 15584561
TI  - Statins: much more than just a lipid-lowering therapy.

PMID- 15584562
TI  - Mortality and morbidity of acute ST segment elevation myocardial infarction in
      the current era.
AB  - BACKGROUND: The mortality rate of acute myocardial infarction has come down
      considerably in the past three decades. In view of paucity of literature on this
      issue, present study was done to find out the in-hospital mortality and 30-day
      event rate in patients with acute ST segment elevation myocardial infarction
      presenting to a tertiary care hospital in India. METHODS AND RESULTS: Consecutive
      patients (n=1320) with the diagnosis of acute ST segment elevation myocardial
      infarction admitted in our institution were included in this study. The in
      hospital mortality and 30-day event rates (mortality, reinfarction, recurrent
      angina and heart failure) were analyzed. The mean age of study population was
      56+/-13 years. There were 1106 (83.8%) males and 214 (16.2%) females; 569 (43.1%)
      patients were smokers, 504 (38.2%) patients had hypertension, 531 (40.2%)
      patients were diabetic and 154 (11.7%) patients had past history of myocardial
      infarction. Anterior wall infarction was present in 752 (57%) patients, 517
      (39.1%) patients had inferior wall infarction, 324 (62.7%) patients had
      associated right ventricular or posterior wall infarction and 51 (3.9%) patients
      had antero-inferior infarction; 1093 patients (82.8%) received thrombolytic
      therapy while 227 patients were not thrombolyzed due to various reasons. Of the
      total 1320 patients, 223 (16.9%) patients died during in-hospital stay while 1097
      patients were discharged from the hospital in stable condition after a mean stay
      of 5.3+/-3.4 days. Thirty-day event rates of death, reinfarction and recurrent
      angina following hospital discharge was 18.8% (134/715 patients) and 36 (5%)
      patients presented with heart failure. CONCLUSIONS: The in-hospital mortality
      rate of acute ST segment elevation myocardial infarction in a tertiary care
      hospital is 16.9%, which is higher compared to reports from the West.

PMID- 15584563
TI  - Mahaim automatic accelerated rhythm: a marker of successful radiofrequency
      ablation.
AB  - BACKGROUND: Mahaim pathways are characterized by the presence of an accessory
      pathway potential-the 'M' potential, at the tricuspid annulus. M potential is a
      very useful guide during radiofrequency ablation of Mahaim pathway. During
      ablation, an accelerated rhythm with ORS morphology, identical to fully pre
      excited QRS complex is observed, and has been labeled as Mahaim automatic rhythm.
      We analyzed this rhythm during radiofrequency ablation of these pathways. METHODS
      AND RESULTS: Eighteen patients with Mahaim accessory pathways were taken up for
      electrophysiology study and radiofrequency ablation. Tricuspid annulus was mapped
      for 'M' potentials and targeted for ablation. Duration of ablation and number of
      ablation attempts were guided by Mahaim automatic rhythm during ablation. Mahaim
      tachycardia was inducible in all. 'M' potentials were recorded in 15/18 patients.
      Radiofrequency energy was delivered at the site where Mahaim accelerated rhythm
      was noticed and was continued till abolition of the rhythm. This resulted in long
      term success. In 3 patients, M potentials were not recordable, and in them other
      methods including 3-dimensional electroanatomical mapping was also not
      successful. CONCLUSIONS: 'M' potential-guided radiofrequency ablation is a useful
      technique. Presence of Mahaim automatic rhythm and its abolition during ablation
      is associated with long-term success of the procedure.

PMID- 15584564
TI  - Assessment of right ventricular diastolic function: does it predict post
      operative course in tetralogy of Fallot.
AB  - BACKGROUND: In some cases of tetralogy of Fallot the post-operative course is
      characterized by episodes of low cardiac output, elevated central filling
      pressures and prolonged ventilation and inotropic support. This may be due to
      impaired diastolic function of the right ventricle despite preservation of
      biventricular systolic function. METHODS AND RESULTS: Sixty-four consecutive
      patients (mean age 7.06+/-4.9 years) undergoing repair of tetralogy of Fallot
      were prospectively studied to assess right ventricular diastolic function.
      'Restrictive physiology' was defined as presence of laminar antegrade diastolic
      pulmonary artery flow (A wave) throughout the respiratory cycle, which was
      coincident with atrial systole. Right ventricle restriction was present in 45/64
      (70%, Group 1) patients and absent in 19/64 (30%, Group 2) patients. There was a
      marked inspiratory augmentation of the pulmonary artery A wave velocity, flow
      integral and duration. Transtricuspid flow revealed significantly lower peak E
      velocity, lower E/A ratio, shorter E deceleration time and higher A velocity time
      integral in those with right ventricular restriction. Biventricular systolic
      function and transmitral flow were normal in all patients. Those with restrictive
      physiology had significantly longer mean inotrope support duration, longer
      ventilation and chest drainage times. Correspondingly, the mean intensive care
      unit stay (56.7+/-9.3 v. 34.7+/-5.38 hours, p<0.01) and mean hospital discharge
      time (9.3+/-2.3 v. 6.2+/-0.5 days, p <0.001) was also significantly longer in
      group 1. CONCLUSIONS: Right ventricular restriction (as seen by laminar antegrade
      diastolic pulmonary artery flow throughout the respiratory cycle) exists in a
      significant subset of patients with tetralogy of Fallot following operative
      repair. Following surgery, such patients have higher inotropic requirement,
      longer ventilation times and longer hospital stay.

PMID- 15584565
TI  - Anticoagulation protocol and early prosthetic valve thrombosis.
AB  - BACKGROUND: [corrected] Prosthetic valve thrombosis is a major cause of morbidity
      and mortality following heart valve replacement with a mechanical valve. METHODS
      AND RESULTS: 538 patients who underwent mechanical valve replacement between
      April 1999 and June 2003 were included in the study. They were divided into two
      groups. Group A (n=245) consisted of patients who underwent mechanical valve
      replacement between April 1999 and June 2001. Anticoagulation was started on the
      first post-operative day and consisted of only oral nicoumalone. Group B (n=293)
      consisted of patients who underwent mechanical valve replacement between July
      2001 and June 2003; enoxaparin was started six hours following surgery in
      addition to oral nicoumalone which was started on first post-operative day.
      Fifteen (6.1%) patients in group A developed early prosthetic valve thrombosis at
      an interval of 4.33+/-0.97 months (range 3-6 months) following surgery. Ten had
      prosthetic valve thrombosis in the mitral position and five had prosthetic valve
      thrombosis in the aortic position. In group B, six (2.1%) patients developed
      early prosthetic valve thrombosis at a median interval of 4.58+/-0.9 months
      (range 3.5-6 months) in the mitral position (p=0.01). CONCLUSIONS: Addition of
      enoxaparin to the anticoagulation regime in the immediate post-operative period
      significantly reduces early prosthetic valve thrombosis.

PMID- 15584566
TI  - Lack of association of heart rate variability parameters with head-up tilt-test
      responses in patients with syncope.
AB  - BACKGROUND: Neurocardiogenic syncope is the most common type of syncope. Head-up
      tilt testing is the investigation of choice for diagnosis of patients with
      neurocardiogenic syncope. In this study, we aimed to findout any association
      between heart rate variability parameters and type of tilt-test response in
      patients with syncope. METHODS AND RESULTS: Forty-nine cases with unexplained
      syncopal attacks were enrolled into our study and were grouped according to the
      tilt-test responses. Tilt test was performed in all patients after excluding
      other causes of syncope. In case of a negative basal tilt-testing,
      pharmacological tilt testing was performed after 30 min of 5 mg sublingual
      isosorbide dinitrate. Holter monitoring was done from the beginning of tilt
      testing upto two hours post-procedure. The heart rate variability parameters
      analyzed were the mean of all coupling intervals between normal beats, the
      standard deviation about the mean of all coupling intervals between normal beats,
      the mean of all 5-min standard deviations of mean of all coupling intervals
      between normal beats, the proportion of adjacent normal R-R intervals differing
      by > 50 ms, the root mean square of the difference between successive RRs, and
      the standard deviation of 5-min mean of all coupling intervals between normal
      beats and ratio between low and high frequencies. CONCLUSIONS: In 35 patients,
      the tilt-test was positive, 16 were cardioinhibitor type (Group 1), four cases
      had a vasodepressor type response (Group 2) and 15 were mixed type (Group 3).
      Fourteen patients had a negative test result. The heart rate variability measures
      did not significantly differ among the study groups. The heart rate variability
      measures were compared between the tilt-test negative (Group 4) and the tilt-test
      positive groups (Groups 1, 2 and 3) and no statistically significant difference
      was found.

PMID- 15584567
TI  - Transcatheter management of patent ductus arteriosus in sick ventilated small
      infants.
AB  - BACKGROUND: Large patent ductus arteriosus can present in infancy with congestive
      cardiac failure and superadded pulmonary infection can necessitate mechanical
      ventilation. Surgical intervention is traditionally indicated for this subset of
      patients. We present our experience of transcatheter coil closure of the patent
      ductus arteriosus in such infants. METHODS AND RESULTS: Five infants weighing
      between 960 gm and 4.1 kg, aged between 17 days and 3 1/2 months were
      mechanically ventilated because of congestive cardiac failure with pneumonia.
      Echocardiography showed patient ductus arteriosus with a size of 1.8 to 4.2 mm
      and adequate ampulla. Bioptome-assisted coil delivery was done and successful
      patient ductus arteriosus closure was achieved in all. There were two instances
      of embolization of coils with successful retrieval and redeployment. All infants
      could be weaned off mechanical ventilation over the next 24-72 hours. A pre-term
      infant developed a Doppler gradient of 25 mmHg in the descending aorta that
      decreased to 12 mmHg five months later. There was no significant obstruction to
      pulmonary artery flow in any child. At three months follow-up, all the five
      infants were asymptomatic with no residual flow across the patient ductus
      arteriosus. CONCLUSIONS: Transcatheter coil closure of moderate to large patent
      ductus arteriosus is possible in sick ventilated infants weighing below 5 kg. It
      may be a better alternative to surgery in selected cases in view of minimal
      morbidity.

PMID- 15584568
TI  - Focal extra strength of a stent causing instent hourglass stenosis: an unusual
      complication.
AB  - We report an unusual complication of a 25 mm long stent, which did not expand at
      all for 1 mm in its proximal segment, while rest of the 24 mm length of the stent
      got fully expanded. Repeated attempts to expand the extremely focal unexpanded
      part of the stent at high pressure led to rupture of the stent balloon and its
      entrapment. We failed to retrieve the balloon using various techniques and the
      patient had to be sent for coronary artery bypass graft surgery.

PMID- 15584569
TI  - Apical hypertrophic cardiomyopathy with apical necrosis and aneurysm formation.
AB  - Apical hypertrophic cardiomyopathy, characterized by giant T-waves and spade
      shaped left ventricular cavity is prevalent in Oriental people, particularly the
      Japanese. We report an asymptomatic case of apical hypertrophic cardiomyopathy
      progressing to myocardial necrosis and aneurysm formation because of the chronic
      myocardial ischemia at the apex.

PMID- 15584570
TI  - Stenting stenosed aortopulmonary collateral arteries in pulmonary atresia with
      ventricular septal defect.
AB  - We present two cases of pulmonary atresia with ventricular septal defect who were
      not suitable for corrective surgery due to absent or hypoplastic native pulmonary
      arteries and were quite symptomatic following shunt surgery. We dilated and
      stented stenosed aortopulmonary collaterals as palliative procedure with
      improvement in oxygen saturation, and significant symptomatic relief.

PMID- 15584571
TI  - 'Rescue' radiofrequency ablation for atrial tachycardia presenting as
      cardiomyopathy in pregnancy.
AB  - A young primiparous lady presented with drug-refractory atrial tachycardia which
      had led to cardiomyopathy. Three attempts with electrical cardioversion were also
      unsuccessful. She was rescued by radiofrequency ablation.

PMID- 15584572
TI  - Torsade de pointes in a case of pheochromocytoma--an unusual presentation of an
      uncommon disease.
AB  - We report the case of a middle aged lady with dilated cardiomyopathy, presenting
      with recurrent syncope due to torsade de pointes. Further evaluation revealed
      that she had a pheochromocytoma which caused the arrhythmia.

PMID- 15584573
TI  - Eptifibatide-induced profound thrombocytopenia.
AB  - We report a case of profound thrombocytopenia, 2 hours following eptifibatide
      therapy which got reversed within 12 hours of discontinuation of eptifibatide.

PMID- 15584574
TI  - Rheumatic carditis: a reappraisal.

PMID- 15584575
TI  - Isolated congenital muscular left ventricular diverticulum in an adult.

PMID- 15584576
TI  - Migration accelerates development of metabolic syndrome--an interesting pedigree.

PMID- 15584577
TI  - Non-pharmacological therapy of hypertension: practical limitations.

PMID- 15584578
TI  - Kawasaki disease.

PMID- 15584579
TI  - Contrast-induced nephropathy and cardiac surgery.

PMID- 15584580
TI  - Identifying congenital hearing impairment. Personal experience based on selective
      hearing screening.
AB  - If all degrees of permanent uni- or bilateral hypoacusis are taken into
      consideration, hearing impairment is the most common congenital disease. Early
      detection of permanent infantile hearing impairment has become extremely
      important in preventive medicine, since steps can be taken with hearing aids and
      rehabilitation to ensure better development of language and higher cognitive
      functions. Aim of this study is to provide a critical review of the time of
      diagnosis of hypoacusis at our audiology laboratory, where two methods were used
      to screen hearing of children with/without risk indicators. Results of
      approximately 10 years' work were re-examined during which time outpatient
      screening was conducted on children referred by colleagues in neonatology and
      paediatrics. All were carriers of congenital risk indicators associated with
      sensorineural and/or conductive hearing loss, based on the Joint Committee on
      Infant Hearing findings, or were suspected of being hypoacusic even if they had
      no known congenital risk factors. Hearing screening was conducted in hospital on
      newborns with no risk factors, within the first few days of birth. Results of the
      present study showed that when selective hearing screening was performed, the
      mean age of high-risk patients diagnosed with hypoacusis was slightly higher than
      that in international guidelines. Moreover, these patients represent
      approximately half the hypoacusic population identified in the study period. The
      other half of congenital hypoacusic subjects identified had no risk indicators
      and there was a significant delay in diagnosis due to later manifestation of
      symptoms indicating hypoacusis, and thus, in turn, delayed referral for hearing
      tests. In contrast, subjects without risk indicators who underwent in-hospital
      hearing screening and proved to be hypoacusic, were diagnosed early. In our
      experience, however, universal screening has considerable disadvantages, such as
      difficulty in covering the entire population, difficulty in follow-up after
      discharge from hospital, and last, but by no means least, significant
      organisational and professional commitments, making it impossible to perform in
      all hospitals. In order to ensure effective hearing screening for congenital
      hearing loss and, thus permit prompt identification of hypoacusic children, use
      of hearing aids and rehabilitation screening should incorporate two aspects.
      First, selection should be compulsory, thereby reducing waiting time between
      collecting case histories and performing outpatient tests; second, hospital
      screening of children without risk factors should be performed whenever possible.
      Integrating these two aspects would make it possible to approach the "utopia" of
      universal hearing screening.

PMID- 15584581
TI  - Anxiety affects vestibulospinal function of labyrinthine-defective patients
      during horizontal optokinetic stimulation.
AB  - Comorbidity of vestibular and anxiety disorders was suggested by epidemiological
      studies and, recently, new insights into potential neural circuits which subserve
      both balance control and emotions, appear to support this hypothesis. In
      particular, disorienting visual surroundings, such as those generated by full
      field moving scenes, equally disrupt postural control of patients with vestibular
      or panic disorders. In the present study, behaviour of body sway was assessed in
      response to an optokinetic stimulation by means of static posturography in 20
      patients with vestibular neuritis (10 patients with normal affect and 10 with
      generalized anxiety disorders, as diagnosed according to the American Psychiatric
      Association criteria), and 20 normal subjects who served as controls. Optokinetic
      responses and vestibulo-spinal function during a full-field, bi-directional
      horizontal optokinetic stimulation, were recorded simultaneously. Labyrinthine
      defective patients with low and high level of anxiety showed a common pattern of
      asymmetric optokinetic reflexes. On the contrary, body sway was found to be
      increased more by eye closure and optokinetic stimulation towards the defective
      labyrinth in patients affected by high level of anxiety as compared to those with
      normal affect and controls. These data confirm the combined effect of anxiety and
      labyrinthine dysfunction on vestibulo-spinal function which is disclosed by both
      visual suppression and disorienting visual contexts.

PMID- 15584582
TI  - Database of benign positional paroxysmal nystagmus.
AB  - Classification of various manifestations of benign positional paroxysmal
      nystagmus, due to canalolithiasis or to cupulolithiasis, as a reaction to
      movements and to the site of detritus, is now possible due to the integration of
      theoretical knowledge (relationships between the semicircular canals and/or
      ampullae and the vestibulo-ocular pathways) with the forms of nystagmus induced
      when the head is placed in various positions. A comparison is made of results in
      patients examined in three Departments, during the past 3 years, and data
      presented in the literature. Findings are presented in a database which enables
      the clinician to compare the standard diagnostic manoeuvres (Dix-Hallpike,
      Pagnini-McClure, Rose) with results obtained by placing the head in alternative
      positions. This approach offers all the information needed to identify the site
      of onset and hence to formulate a correct diagnosis, thus directly indicating the
      most appropriate liberating or repositioning manoeuvre or--in the case of a
      suspected central lesion--to suggest further tests. Moreover, it is suggested
      that this table could become a useful tool for teaching purposes.

PMID- 15584583
TI  - New techniques and technology to repair cerebrospinal fluid rhinorrhea.
AB  - Cerebrospinal fluid rhinorrhea occurs as a result of abnormal communication
      between the subarachnoid space and the pneumatized portion of the skull base, the
      paranasal sinuses and the middle ear. Conservative measures may be sufficient in
      the management of cerebrospinal fluid rhinorrhea, but, in some cases, surgical
      treatment may be required. Transnasal endoscopic techniques are constantly being
      used in preference to the intra- and extracranial approaches. Recently, image
      guidance systems have been adopted in neurosurgery, skull base and paranasal
      sinus surgery. The present report refers to 4 cases of nasal cerebrospinal fluid
      rhinorrhea leak successfully treated with a transnasal endoscopic approach using
      various techniques and materials to close the bone defect, in 2 of which, the
      navigation system (Stealth Station Treon ENT Image Guidance System with Landmark
      X, Software, Medtronic, XOMED, Jacksonville, FL, USA) was also used. In all
      cases, correct localization and repair of the leak was achieved and no major
      complications occurred. Following a review of the literature, the Authors
      conclude that, at present, transnasal endoscopic repair of cerebrospinal fluid
      rhinorrhea is the surgical treatment of choice when the techniques and materials
      are correctly used. Furthermore, preliminary findings indicate that it is
      possible to make routine use of the navigation systems and that this technology
      may be usefully employed, above all, in the management of cerebrospinal fluid
      leaks.

PMID- 15584584
TI  - Total intravenous anaesthesia in endoscopic sinus-nasal surgery.
AB  - Aim of this randomized study (64 patients) was to improve the control of bleeding
      during functional endoscopic sinusal surgery by means of controlled hypotension
      achieved through either total intravenous anaesthesia using remifentanyl and
      propofol (27 patients), or inhaled using isoflurane and fentanyl (37 patients).
      The following parameters were monitored before administration of anaesthesia
      (T0), then after 15 (T1), and 30 minutes (T2): systolic, diastolic, and mean
      arterial pressure; heart rate; concentration of tele-exhaled carbon dioxide
      (PetCO2) and percentage of peripheral saturation of haemoglobin (SPO2); bleeding
      according to the Fromme-Boezaart scale at T2. Mean arterial pressure values were
      maintained between 60-70 mmHg throughout surgery. At T0, systolic arterial
      pressure, diastolic arterial pressure and mean arterial pressure values were seen
      to overlap in the two groups. Both types of anaesthesia were effective in
      reducing the pressure values of T0-T1 and T1-T2 trends (p<0.0001). Systolic
      arterial pressure at T1 is lower with total intravenous anaesthesia compared to
      isoflurane and fentanyl (p=0.02). PetCO2 and heart rate show a decreasing trend
      independently of the type of anaesthesia employed. In conclusion, the hypotensive
      effect of total intravenous anaesthesia and of isoflurane and fentanyl is
      equivalent, but only total intravenous anaesthesia is effective in reducing
      bleeding during functional endoscopic sinusal surgery.

PMID- 15584585
TI  - An extended use of the sentinel node in head and neck squamous cell carcinoma:
      results of a prospective study of 100 patients.
AB  - Most studies concerning the use of the sentinel node technique in head and neck
      cancers have included clinically N0 patients with primary early stage tumours of
      the oral cavity or upper part of oropharynx; furthermore, node sampling has been
      performed during the same session, but separately from the tumour. The
      perspective of avoiding unnecessary neck dissection, without increasing the risk
      of delayed diagnosis of lymph node metastasis, is rewarding, not only for early
      stage tumours of the oral cavity but also for tumours in advanced stages and/or
      at different anatomic sites. In the attempt to establish the reliability of
      extended use of the sentinel node technique, 100 consecutive untreated patients
      (from 1999 to 2002) with tumours located in the oral cavity, oropharynx,
      hypopharynx and larynx, at any T stage, entered the study. N+ patients with
      paramedian tumours and contralateral clinically negative nodes were also
      enrolled. After injection of the 99mTc albumin microcolloid, pre- and intra
      operative evaluations with a gamma-probe were done. N0 patients (59) were
      submitted to mono- or bilateral selective neck dissection; the N+ patients (41)
      received homolateral dissection of all levels and contralateral selective
      dissection. An en bloc resection of the tumour was performed both in N0 and N+
      patients. In the N0 group, histological examination showed no evidence of
      metastases in "hot" nodes in 34 patients and also the remaining nodes were
      negative. Metastases were found in one or more of the gamma-probe positive nodes
      (14 cases), or in a closely located node at the same level (2 cases) or in a node
      close to a "hot" area of the submandibular salivary gland (1 case). In 8
      patients, lymphoscintigraphy did not identify any sentinel node and histology of
      all lymph nodes was negative for metastases. In the N+ group, no metastases were
      found in the sentinel nodes of 21 patients and also the remaining nodes were
      negative; in 4 patients, metastases were found in sentinel nodes. In 16 patients,
      lymphoscintigraphy did not identify any sentinel node and histology of all lymph
      nodes was negative for metastases. In no patients were metastases found outside
      the level containing the lymph node identified as sentinel by the gamma-probe. In
      conclusion, the strategy of the sentinel node is reliable, but, to be confirmed
      as a standard approach, it requires trials with a larger number of patients. The
      technique requires a multidisciplinary and well "amalgamated" team. It may likely
      be used also in T3 and T4 oro-hypopharyngeal and laryngeal primary tumours and to
      determine surgical treatment of the contralateral neck in patients with N2a, N2b,
      N3 on T close to the midline.

PMID- 15584586
TI  - Reconstruction of partially amputated external ear with costal cartilage graft:
      case report.
AB  - Many causes are responsible for secondary anomalies of the outer ear, such as:
      car accidents, sport- or work-related accidents, assaults, bites from animals or
      humans, benign or malignant tumours, burns and the effects of surgical
      interventions of the ear (plastic surgery on the ear or attempts at correction of
      primary malformations of the ear). The anatomical complexity of the ear makes its
      reconstruction particularly complicated with post-operative results that are
      often disappointing. The Authors describe their experience in the reconstruction
      of a partially amputated outer ear following a dog bite. The therapeutic protocol
      required various surgical stages. Initially, a cutaneous expander was applied at
      the level of the mastoid in order to ensure a sufficient quantity of local skin.
      The second stage was to remove cartilage from the ribs, followed by construction
      of a cartilaginous model of the ear and its insertion into the subcutaneous
      mastoid region after removal of the cutaneous expander and any residual ear
      cartilage. The last stage was to separate the neo-formed outer ear from the
      mastoid skin with the insertion of a cartilage graft to the posterior region of
      the reconstructed ear. This graft was covered by the occipital fascia rotated at
      180 degrees and by a skin graft removed from the pubis. The postoperative result
      was satisfactory with recuperation of a good aesthetic appearance of the ear. Aim
      of the present report is to describe the surgical technique employed in the
      reconstruction of secondary anomalies of the ear and to highlight errors
      committed during this procedure. These considerations have allowed us to stress
      some fundamental elements in the reconstruction of the ear. In particular, the
      watershed was the awareness that we had to create a cartilaginous model that
      respected, as far as possible, the anatomy of the outer ear with all its ridges,
      trenches and cavities. This as well as ensuring a sufficient quantity of local
      skin in order to cover the cartilaginous graft and, therefore, reduce the risk of
      exposing the cartilage and subsequent infection, to guarantee an optimal end
      result.

PMID- 15584587
TI  - Clear cell carcinoma of minor salivary gland of the tongue.
AB  - The case of a clear cell carcinoma of a minor salivary gland, at the basis of the
      tongue, is described, which represents 1% of malignant tumours of salivary
      glands. The biological behaviour is not very aggressive and development, which is
      very slow, is usually asymptomatic, and, indeed, the tumour often reaches
      considerable dimensions before being diagnosed. There are rare cases of local
      recurrence and distant metastases. Cases of salivary glands which have become
      sites of secondary localization of a clear cell tumour, originating in the
      kidneys, have been described. The interest in the form described here stems from
      the slow evolution and the considerable dimensions reached by the tumour before
      being diagnosed, despite development in a breathing or digestive area such as the
      oralpharyngeal tract. In the present case, computed axial tomography and nuclear
      magnetic resonance were used to reach the diagnosis. The patient was submitted to
      surgical treatment. In the differential diagnosis, it is necessary, from a
      pathological point of view, to take into consideration other neoplastic
      formations, such as acinar cell adenocarcinoma, epithelial-myoepithelial
      carcinoma, clear cell oncocytoma, sebaceous adenoma and sebaceous carcinoma.

PMID- 15584588
TI  - Parathyroid cysts: description of two cases and review of the literature.
AB  - Parathyroid cysts are a relatively rare cause of neck swelling, and their anatomo
      pathological and clinical features are still under debate. Two types of
      parathyroid cysts have been recognized: the non-functioning or essential forms,
      which are more frequent, and the adenomatous or functioning parathyroid cysts,
      which are rarer and cause hyperparathyroidism. Two cases of parathyroid cysts are
      reported and the treatment is described bearing in mind the various therapeutic
      procedures proposed in the literature. Attention is focused on pre-operative
      differential diagnosis from other masses, in the same area, and, to this end, the
      importance is stressed of assaying parathyroid hormone levels in the cystic
      fluid, obtained by fine-needle aspiration, and correlating these values with
      serum levels of the hormone.

PMID- 15584589
TI  - Bruxism: two case reports.
AB  - The present report refers to two patients presenting with grinding of the teeth
      (bruxism). A brief review is made of the literature concerning the aetiology of
      the disease, the clinical manifestations and diagnosis, as well as the
      therapeutic approach.

PMID- 15584590
TI  - [Thrombolytic therapy for pulmonary thromboembolism].

PMID- 15584591
TI  - [The diagnosis and treatment of coronary heart disease in chronic renal failure].

PMID- 15584592
TI  - [Role of cationic trypsinogen gene (PRSS-gene) mutations in the pathogenesis of
      chronic pancreatitis].

PMID- 15584593
TI  - [The diurnal blood pressure and the EchoCG parameters of the left ventricle in
      patients with diabetic nephropathy].
AB  - The purpose of the study was to examine the geometry of the left ventricle (LV)
      in patients with type 1 diabetes mellitus (DM) in relation to the 24-hour profile
      of blood pressure (BP) and urinary albumin excretion. The study covered 60
      patients with type 1 DM and normal creatinine clearance, including 20 patients
      with normal albuminuria, 23 with microalbuminuria, and 17 with proteinuria. 24
      hour BP monitoring was performed oscillometrically; myocardial structural
      parameters were studied by echoCG. LV hypertrophy (LVH) was found in 1 patient
      with normal albuminuria and in 8 with proteinuria (5, 30.4, and 47%,
      respectively; chi2 = 9.3; p = 0.09). The frequency of concentric and eccentric
      types of LVH was equal. In patients with a lower nocturnal BP decrease, the LV
      myocardial mass index (LVMMI) and relative posterior wall thickness (RPWT) were
      higher than those in other patients (LVMMI, 120.8 +/- 24.6 and 95.0 +/- 23.1
      g/m2, respectively; p < 0.001; RPWT, 0.35 +/- 0.06 and 0.31 +/- 0.06,
      respectively, p = 0.013). Multifactorial stepwise regression analysis has
      indicated that age, male sex, and proneinuria directly affected LVMMI (R2 = 0.70;
      p < 0.001). Diastolic BP, autonomic neuropathy, and hemoglobin levels were found
      to be independent predictors of RPWT (R2 = 0.70; p < 0.009). The findings suggest
      that there is a close relationship between diabetic neuropathy and LV remodeling
      in patients with type 1 DM. This relationship may be operative via factors, such
      as arterial hypertension, altered diurnal BP profile, autonomic neuropathy, and
      anemia.

PMID- 15584594
TI  - [Endovascular treatments in coronary heart disease patients with restenosis after
      primary ballon angioplasty].
AB  - The study was undertaken to comparatively assess the results of stenting and
      transluminal balloon angioplasty (TBAP) of coronary arteries in patients with
      chronic forms of coronary heart disease concurrent with restenosis of primary
      TBAP. The data on 77 patients undergone endovascular procedures for restenosis of
      prior primary TBAP of coronary arteries at the Moscow Research and Practical
      Center of Interventional Cardioangiology in March 1997 to May 2003 were analyzed.
      Group 1 comprised 35 patients with a stent implanted at the site of coronary
      restenosis; Group 2 included 42 patients undergone repeated TBAP. These groups
      did not significantly differ in main clinical and functional characteristics, the
      extent coronary bed lesion, the number of diseased arteries and the morphological
      type of a coronary lesion (p < 0.05). The angiographic success of secondary TBAP,
      as well as coronary stenting was 100%. Survival was 100% in the late period. A
      control examination revealed the clinical picture of angina on exertion in 57.1%
      and 76.2% of the patients in Groups 1 and 2, respectively (p = 0.039). In the
      late period, a satisfactory angiographic result of coronary stenting was revealed
      in most cases (74.3 and 35.7% in Groups 1 and 2, respectively); restenosis was
      detected in 20 and 59.5% of cases, respectively (p < 0.01); occlusion in 5.7 and
      4.8% (p > 0.05). Need for repeated interventional and surgical (aortocoronary
      bypass surgery) procedures was significantly less after coronary stenting than
      that after repeated TBAP (20 and 40.5%, respectively). In the late period, the
      factors significantly increasing a risk for in-stent restenosis were
      hypercholesterolemia (cholesterol > or = 5.5 mmol/l); the length of restenosis of
      an operated segment was > or = 18 mm and that of a stent > or = 20 mm. It is
      expedient to use coronary endroprosthesis to reduce the incidence of repeated
      restenosis and needs for repeated procedures for myocardial revascularization in
      the late period.

PMID- 15584595
TI  - [Psychosomatic ratios and their correction in the autonomic dysfunction of the
      sinus node].
AB  - The study was undertaken to examine the ratio of mental to somatic disorders in
      patients with autonomic sinus nodal dysfunction (ASND) and the capacities of
      correction of revealed disorders with the atypical benzodiazepine drug
      clonazepam. Thirty-two patients with ASND were examined. The diagnosis of ASND
      was verified by 24-hour ECG monitoring and transesophageal atrial pacing, by
      performing autonomic cardiac block with atropine and obsidan. In addition to
      physical examination, heart rhythm variability was studied during relaxed and
      intensive wake; psychological studies using the conventional tests were
      conducted, and autonomic disorders were explored by means of original scored
      somatic, hyperventilation) questionnaires. After examination, the patients
      received a 1.5-to-2-month course of therapy with clonazepam in a daily dose of
      1.5-2 mg. The study has revealed that clinical symptomatology in ASND is greatly
      determined by psychosomatic disorders. ASND was marked by anxious depressions in
      combination with inadequate peripheral (to a greater extent, sympathetic)
      neurovegetative exposures with the simultaneous activation of cerebral ergotropic
      effects. The use of clonazepam in ASND greatly improved its clinical picture, by
      eliminating, in the overwhelming majority of cases, clinical symptoms, including
      rhythm and conduction disturbances that are characteristic of ASND.

PMID- 15584597
TI  - [The content of biogenic amines in the lymphocytes in bronchial asthma].
AB  - Serum serotonin and histamine were examined for their effects on lymphocytic
      dystrophic processes. During an exacerbation, there was an increase in the plasma
      concentration of biogenic amines (BGA) in patients with atopic and infective-and
      allergic bronchial asthma. The elevated levels of BGA affected the activity of
      lymphocytes that were, on an exacerbation, in the functional stress accompanied
      by a derangement of adaptive processes that ended in cell dystrophy.

PMID- 15584596
TI  - [Pulmonary hypertension, involvement of the right and left cardiac parts in
      patients with ankylosing spondylarthritis].
AB  - The literature states that pulmonary hypertension (PH) may develop in ankylosing
      spondylarthritis (AS); however, there are virtually no evidence for its incidence
      and the specific features of lesions of the right and left cardiac portions. This
      study was undertaken to determine the incidence of PH and its specific features
      in patients with AS. Fifty-five patients with AS were examined. There were
      prevalent patients with predominantly spinal lesions (50.9%), moderate
      progression of the disease (61.8%), and Grade III sacroileitis (49.1%). PH was
      detected in 70.96% of the patients, hypertrophy of the right ventricle (RV) was
      observed in 47.3%, RV dilation was in 34.5%. There were increases in the end
      systolic size and volume of the left ventricle (LV) in patients with AS (p < 0.05
      and p < 0.05, respectively), ventricular septal thickening (p < 0.05), and a
      tendency for the posterior LV wall to be thickened. LV diastolic dysfunction
      occurred in 25.9% of the patients with AS. The found changes were interrelated
      with the duration of disease, the involvement of the vertebral column, the
      thoracic part in particular. Thus, the high incidence of PH was ascertained in
      patients with AS. The study confirms that echocardiography is of high informative
      value in the detection of PH and right cardiac changes in patients with AS, which
      shows this method to be screening in identifying the above pathology.

PMID- 15584598
TI  - [Thrombocytic hemostasis in hypertensive patients with metabolic syndrome and its
      correction with lovastatin].
AB  - The objective of the study was to evaluate the efficiency of lovastatin
      correction of dyslipidemia and impaired intravascular platelet activity (IPA) in
      patients with arterial hypertension (AH) concurrent with metabolic syndrome (MS).
      Eighteen patients were given lovastatin for a month. The time course of changes
      in anthropometric parameters, blood lipid spectrum, plasma and lipid
      peroxidation, antioxidative protectiveness of the liquid blood part and
      platelets, and IPA were assessed. The results were processed by Student's test
      and correlation analysis. Lovastin was ascertained to correct dyslipoproteinemia
      and peroxidation syndrome and to optimize the intrathrombocytic mechanisms
      responsible for their function regulation in patients with AH + MS. Lovastatin
      inhibits in vivo increased platelet activity. These effects may be stabilized
      during its use. Body weight loss and diminished insulin resistance in patients
      with AH concurrent MS require long use of lovastatin along with low-calorie diet
      and exercises.

PMID- 15584599
TI  - [Thrombocytic dysfunctions and potentialities of their differential correction in
      chronic viral hepatitis].
AB  - The paper presents the results of examination in 88 patients with chronic viral
      hepatitis (CVH), the parameters of spontaneous and induced platelet aggregation
      (IPA), cyclic nucleotides (cAMP and cHMP) in the platelets, and the plasma levels
      of thrombocyte-specific peptides--beta-thromboglobulin and thrombocytic factor IV
      in dynamics of the first administration of alpha-interferon (alpha-IFN) and 24
      week interferon therapy. According to the values of IPA, the patients with CVH
      are a heterogeneous group with a predominance of cases of diminished aggregation.
      The first administration of alpha-IFN causes heterodirectional changes in the
      functional activity of platelets with a general tendency for their normalization.
      Supplementation of curantyl in case of increased IPA leads to a more rapid and
      profound normalization of platelet activity, which is of value in cases at risk
      for thrombotic complications.

PMID- 15584600
TI  - [Heterogeneity of low-density lipoproteins in cholesterolosis of the gallbladder
      and cholelithiasis].
AB  - The heterogeneity of serum low-density lipoproteins (LDL) was studied in patients
      with cholelithiasis (CL) and gallbladder cholesterolosis (GBC). Native gradient
      (3-12%) polyacrylamide gel electrophoresis was used, followed by densitometric
      scanning and analysis; a correlation analysis of the levels of cholesterol
      levels, the body-mass index (BMI), and age was made. Various heterogeneity of LDL
      was revealed in CL and GBC. In the group of patients with GBC, the subfraction
      spectrum of LDL was characterized by a predominance of minor dense particles of
      LDL (Rf = 0.171 +/- 0.003), which significantly differed from that in the
      patients with CL (Rf = 0.146 +/- 0.004) and the controls (Rf = 0.144 +/- 0.013, p
      < 0.05). The increased levels of total cholesterol were associated with the
      changes in the subfraction spectrum of LDL with a moderate correlation (r = 0.596
      and r = 0.343, respectively). However, a correlation was found between the
      variability of LDL, BMI, and age (r = 0.533 and r = 0.363, respectively) whereas
      in GBC it was absent (r = 0.148 and r = 0.117). The findings suggest that the
      minor dense subfractions of LDL are a risk factor for GBC irrespective of age and
      body mass. The modified minor particles of LDL more rapidly penetrate than other
      LDL fractions into the gallbladder tissue, where the gallbladder wall is
      intensively captured by macrophages, and participate in the formation of foamy
      cells. In CL, the increase in total cholesterol levels is not followed by so
      marked changes in the structure of LDL. The much lower proportion of minor dense
      particles that are components of LDL is a cause of the low entry of
      apolipoproteins into the gallbladder wall in CL as compared with GBC.

PMID- 15584601
TI  - [Use of tykveol in the treatment of impaired biliary tract function in patients
      with chronic non-calculous cholecystitis].
AB  - The therapeutic efficacy of tykveol was evaluated in 22 patients with chronic non
      calculous cholecystitis and/or dyskinesia of the biliary tract (BT) concurrent
      with gallbladder deformity (GD). Supplementation of tykveol to the combined
      therapy in the patients with chronic non-calculous cholecystitis concurrent with
      GD was shown to exert a pronounced therapeutic effect. This caused positive
      changes in clinical symptoms and BT function, diminished the lithogenic propertes
      of bile. With the use of tykveol, recovery of neurohumoral regulation is an
      important factor that improves biliary tract function, as evidenced by decreased
      gastrin secretion.

PMID- 15584602
TI  - [Clinical value of soluble tumor necrosis factor-alpha receptors in patients with
      systemic lupus erythematosus].
AB  - The study was undertaken to examine the clinical value of serum levels of soluble
      receptors of tumor necrosis factor-alpha with a molecular mass of 55 kDa (rTNF
      alpha-55R) in patients with systemic lupus erythematosus (SLE). The serum level
      of rTNF-alpha-55R was measured by enzyme immunoassay (a "Quantikine" set, R&D
      System, USA) in 73 patients with SLE and 22 donors. In the patients, the mean
      level of rTNF-alpha-55R was significantly higher than that in donors. Higher
      serum levels of rTNF-alpha-55R were noted in 43.8% of the patients with SLE.
      There was a correlation between the level of rTNF-alpha-55R and the progression
      of SLE (p < 0.05), the exacerbation (p < 0.05), and the clinical manifestations
      of the disease (cardiac valvular apparatus damage, active lupus nephritis). rTNF
      alpha-55R are a marker of the progression and exacerbation of SLE and reflects
      that there is a prognostically poor factor, i.e. the involvement of the kidneys
      in a pathological process.

PMID- 15584603
TI  - [Non-steroidal anti-inflammatory drugs and tramadol in the treatment of
      osteoarthrosis deformans in patients with arterial hypertension].
AB  - The prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can
      be manifested by the decreased efficiency of antihypertensive therapy. The
      tactics of their differential use in relation to the its effect on blood pressure
      (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not
      been developed for the most effective and safe therapy. In this connection, it is
      extremely urgent to study the comparative safety of used NSAIDs as to their
      prohypertensive effect and to work out the management of patients with AH and OA.
      Ninety-eight patients with second-third degree OA of the knee and hip joints
      concurrent with the pain syndrome and first-second grade AH were followed up.
      Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a
      control group, the analgesic tramadol was supplemented to the therapy. AH was
      controlled by enalapril monotherapy. In groups of patients receiving diclofenac,
      arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases
      of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an
      inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the
      prohypertensive effect of these drugs; this trend was most pronounced in the
      diclofenac and arthrotec groups. Despite its marked prohypertensive effect,
      nimesulide did not impair circadian BP variations. The central-acting analgesic
      tramadol exerted no prohypertensive effect and it did not increase BP values. The
      prohypertensive effect of the tested NSAIDs and tramadol increases in the
      following order: tramadol, ketoprofen, meloxicam, nimesulide, arthrotec,
      diclofenac.

PMID- 15584604
TI  - [Treatment of autoimmune hepatic diseases].
AB  - The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis
      for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune
      hepatitis, immunosuppressive therapy induces and maintains persistent remission
      in most patients while in primary biliary cirrhosis and primary sclerosing
      cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is
      used as the basic drug in predominantly occurring intrahepatic cholestasis. The
      treatment of cross autoimmune syndromes generally requires the choice of a
      combination of drugs.

PMID- 15584605
TI  - [Complex treatment of patients with the diabetic foot].
AB  - To improve a complex surgical treatment of patients with the diabetic foot (DF),
      46 patients with examined and treated this condition were. According to the
      treatments used, the patients were divided into 2 groups: study and control ones.
      The study group (n = 28) received current complex treatment using laser and
      immune therapies. The control group had routine therapy. In addition to
      hypoglycemic, disintoxication, and antibacterial therapy, a complex of drugs,
      which included antioxidants, thioctic acid preparations, agents that improved
      regional blood flow and microcirculation (sulodexide, pentoxyfilline), and
      immunomodulators was used to treat patients of the study group. In this group,
      physiotherapeutic techniques, such as electrophoresis with trental, ascorbic
      acid, and thymaline and intravenous laser radiation, were applied. Laser units
      were employed. Pathological tissues were dissected and evaporated with a focused
      and partially defocussed laser ray. Then local laser therapy was performed; after
      active granulation tissue appeared, plastic repair of a wound with local tissues
      was applied. Cytological studies of touch smears indicated that in patients with
      diabetes mellitus who had received the complex therapy, pyonecrotic wounds and
      trophic ulcers were cleansed of wound detritus and fibrin within shorter periods
      (12.6 +/- 2.1 days) than those in the patients of the control group (16.3 +/- 2.6
      days). The time of wound healing was 27.3 +/- 2.8 days and 35.4 +/- 3.9 days),
      which also favors the new treatments of this pathology.

PMID- 15584606
TI  - [Lymphoepithelial cyst of the thyroid].

PMID- 15584607
TI  - [Prolonged treatment of multiple Echinococcus granulosus infection].

PMID- 15584608
TI  - Hospitals are creating sport medicine centers.

PMID- 15584609
TI  - How will hospitals work with concierge docs?

PMID- 15584610
TI  - Critical impact analysis of how providers affect lives builds loyalty.

PMID- 15584611
TI  - Hospitals search for better ways to collaborate with their physicians.

PMID- 15584612
TI  - Novel genetic approaches to the resolution of complex diseases.
AB  - Up to very recent times, genetics as been the science of monogenic disorders
      based on Mendelian laws. Completion of human genome sequencing as well as that of
      other species, including mainly the mouse and rat are now providing the
      opportunity to resolve complex diseases, i.e., those based on several genes and
      significantly modified by the environment. This complex paradigm, however,
      requires novel strategies. We propose an integrated use of experimental genetic
      animal models, with that of relatively isolated human populations with large
      families and accessible genealogical data. Foreseeably, genetics will be part of
      this novel medicine in which the prediction of diseases will be based on
      individual genomic makeup.

PMID- 15584613
TI  - [Treatment in the primary prevention of stroke--still not fully used option].
AB  - Several studies have shown that pharmacological treatment of systolic-diastolic
      hypertension or isolated systolic hypertension in elderly persons would result in
      several years in a significant decrease (more than 40%) of stroke. Occurrence of
      strokes decreased in the Czech Republic in years 1985 till 2002 by more than 40%,
      which represents about two thirds of the decrease observed in the USA.
      Nevertheless, we cannot be satisfied with the treatment of hypertension in the
      Czech Republic because only 18% of patients are effectively treated for the
      hypertension, with BP < 140/90 mm Hg. Not well controlled hypertension results
      namely from the minimal use of the combination treatment. From the point of
      prognosis for the hypertensive patients older than 50 years, the level of
      systolic pressure is more important than the diastolic pressure. The risk of
      development of the stroke rises from the level of systolic blood pressure 115
      mmHg almost linearly. Calcium channel blockers or diuretics represent the most
      appropriate therapy of the isolated systolic hypertension of elderly patients.
      The risk of stroke is higher also in persons with elevated blood pressure in the
      morning. That is why in elderly patients the use of drugs effectively controlling
      blood pressure during 24 hours is necessary. Recent studies (HOPE study, PROGRESS
      study) have demonstrated that the reduction of blood pressure decreases the
      occurrence of stroke not only in hypertensive patients, but also in the
      normotensive persons during the primary and secondary prevention. Review data
      show that 27% of ischemic strokes and 57% of hemorhagic strokes, which happened
      in the "treated" hypertensive patients, are due to not well controlled
      hypertension. Missing treatment of hypertension is responsible for 22.8% of
      strokes in men and 25.4% in women. The given data show a big reserve for the
      possibility to decrease further the stroke incidence in the population.

PMID- 15584614
TI  - [Genetic causes of the thyroid carcinomas].
AB  - Thyroid carcinomas represent only 1% of all human malignancies, but more than 90%
      of endocrine tumors. It can be histologically divided into papillary, follicular,
      anaplastic or medullary thyroid carcinomas. Here we report the genetic causes of
      the development of these tumors. For papillary thyroid carcinoma formation of
      fused genes of tyrosine kinases (RET proto-oncogene, NTRK1 proto-oncogene and met
      proto-oncogene) with other genes is typical. They can activate these kinases and
      induce mutation in BRAF gene. The presence of PAX8/PPARgamma fused gene and ras
      mutations are important in the development of follicular thyroid carcinoma.
      Anaplastic thyroid carcinoma derives from the dedifferentiation of papillary and
      follicular carcinomas as a consequence of mutation or loss of heterozygozity in
      p53 gene. Medullary thyroid carcinoma comes from parafollicular C-cells, where
      point somatic and germ-line mutations (in familial form of medullary thyroid
      carcinoma or in multiple endocrine neoplasia type 2) in the RET proto-oncogene
      determine its development. Identification of these specific genetic alternations
      for each type of carcinoma can contribute to precision of the diagnosis,
      explanation of the origin of carcinomas, establishment of prognosis of the
      disease or in future as a tool for the target gene therapy.

PMID- 15584615
TI  - [Regression of atherosclerotic plaques during treatment with statins].
AB  - Atherosclerosis and its complications represent the most frequent cause of death
      in the developed countries. Pathophysiology of the atherosclerosis development
      has been described in details. Much less is known what is the extent of
      reversibility of pathophysiological changes. Several angiographic studies have
      proved that statin administration can slow down the progression of the coronary
      arteries atherosclerosis. However, only intravascular ultrasound analysis is able
      to give a detailed description of atherosclerotic plaque development during the
      treatment with statins. Studies have shown apparent stagnation of atherosclerosis
      progression and in voluminous plaques also signs of regression. Beside changes in
      the size of atherosclerotic plaques, alteration in their chemical composition was
      described. During the treatment with statins, amount of lipids in plaque
      decreases, which indicates the stabilisation of plaques. Plaques are less prone
      to a rupture and to the subsequent development of an acute coronary syndrome.
      Beside statins, which influence namely LDL cholesterol, attention is given to
      drugs enabling to elevate HDL cholesterol level, because it is the way in which
      cholesterol is transported from tissues back to the liver. It appears that
      elevation of HDL cholesterol level could bring about more effective regression of
      atherosclerotic plaques and together with stagnation of the plaque progression it
      can significantly improve the conservative methods in the treatment of
      atherosclerotic disease of the coronary and peripheral arterial system.

PMID- 15584616
TI  - [Nutrition genomics].
AB  - The importance of nutrition for human health and its influence on the onset and
      course of many diseases are nowadays considered as proven. Only the recent
      development of molecular biology and biochemical methods allows the elucidation
      of the molecular mechanisms of diet constituent actions and their subsequent
      effect on homeostatic mechanisms in health and disease states. The availability
      of the draft human genome sequence as well as the genome sequences of model
      organisms, combined with the functional and integrative genomics approaches of
      systems biology, bring about the possibility to identify alleles and haplotypes
      responsible for specific reaction to the dietary challenge in susceptible
      individuals. Such complex interactions are studied within the newly conceived
      field, the nutrition genomics (nutrigenomics). Using the tools of highly parallel
      analyses of transcriptome, proteome and metabolome, the nutrition genomics
      pursues its ultimate goal, i.e. the individualized diet, respecting not only
      quantitative and qualitative nutritional needs and the actual health status, but
      also the genetic predispositions of an individual. This approach should lead to
      prevention of the onset of such diseases as obesity, hypertension or type 2
      diabetes, or enhance the efficiency of their therapy.

PMID- 15584618
TI  - [Nuclear factor kappa B in the treatment of inflammatory and tumor diseases].
AB  - Since its discovery in 1986 nuclear factor kappa B attracted attention of
      scientists all over the world. Intensive research has proved its indisputable
      role in pathogenesis of particularly inflammatory and tumor diseases and revealed
      many possibilities in the modulation of its function. For some of the modulators
      distinct therapeutic effects have been proved in in vitro and in vivo studies or
      even in the clinical trials, some of them are still to be tested. One may expect
      wide use of different inhibitors or modulators of nuclear factor kappa B in
      various indications, which will markedly enhance the therapeutic effect.

PMID- 15584619
TI  - [Evaluation of the clinical effectivity and toxicity of the FDN regimen
      (fludarabin, mitoxantron, dexamethason) in patients with follicular lymphoma].
AB  - BACKGROUND: One of the perspective therapeutic possibilities in follicular
      lymphomas (FL) is the fludarabine-based regimen FND (fludarabine, mitoxantron,
      dexamethason). However serious signs of myelotoxicity and significant
      immunosuppression with appearance of the opportunistic infections were described
      after the fludarabine treatment. METHODS AND RESULTS: Follicular lymphoma
      patients with advanced disease grade I-II were treated with FND (6-8 cycles). The
      immunotoxicity was evaluated by measuring of immunoglobuline levels (IgA, IgG,
      IgM) and that of lymphocytes subpopulations (CD3+, CD4+, CD8+, CD20+, CD56+) in
      peripheral blood. The myelotoxicity was evaluated by cultures of progenitor cells
      (CFC and LTC-IC). Totally 34 patients (median age 55.5 years) were evaluated, the
      overall response was 72% (CR 61%, PR 11%, progression 28%). 73% patients of 11
      after 6-8 FND show persisting CR (27% relapsed) with median follow-up about 15
      months. The dominating toxicity was myelotoxicity. The leucopenia grade III-IV
      occurred in about 30% cycles. Because of toxicity it was necessary to reduce
      doses of FND in 10% cycles and this treatment had to be finished ahead of
      schedule in 29% patients. The significant immunotoxicity was found only in the
      decrease of whole lymphocyte population (p < 0.05) and of IgG level (p < 0.05).
      The decrease of lymphocyte subpopulations did not reach any statistical
      significance. The long-term myelotoxicity caused the decrease of LTC-IC that had
      a clinical correlation with the very difficult mobilization of PBSC. CONCLUSIONS:
      FND is efficient in treatment of follicular lymphoma. However myelotoxicity seems
      to be limiting. Myelotoxicity doesn't allow administering scheduled dose of FND
      in substantial amount of patients, long-term myelotoxicity complicates PBSC
      mobilization. Lymphotoxicity is apparent, but seems not to be clinically
      important.

PMID- 15584620
TI  - [Monitoring the important mycotoxin biomarkers (ochratoxin A, aflatoxin M1) in
      the Czech population].
AB  - BACKGROUND: In among mycotoxins, secondary metabolites of toxinogenic moulds,
      ochratoxin A and aflatoxins occupy a prominent place. These mycotoxins have been-
      as etiologic agents-- associated with a wide numbers of acute and chronic human
      diseases including mycotoxicoses like Balkan endemic nephropathy or liver cancer.
      While the risk of acute toxic effects of ochratoxin A and aflatoxin B1 is usually
      considered to be minimal in the Czech Republic, the situation is different as far
      as the risk of the late toxic effects (particularly carcinogenic), which result
      from a single or repeated intake of low doses of these mycotoxins from foodstuffs
      is concerned. METHODS AND RESULTS: The presence of ochratoxin A and aflatoxins in
      human environment has been monitored within the program "Monitoring the health
      state of the population". As for ochratoxin A, 2206 samples of blood serum were
      investigated, 2077 (94 %) of them turned out to be positive (with levels > or =
      0.1 microg x l(-1)), the average was 0.28 microg x l(-1), the median was 0.2
      microg x (l(-1), and the percentile (90%) was 0.5 microg x l(-1). The ochratoxin
      A levels ranged from 0.1 to 13.7 microg x l(-1) of sera. The presence of
      ochratoxin A was also analyzed in 30 samples of human kidneys; 12 samples were
      positive (with levels > or = 0.1 microg l(-2), the average was 0.07 microg x kg(
      1), the median was 0,05 microg x kg(-1). As for aflatoxins, in 1997-1998 the
      presence of aflatoxin M1 was investigated in 205 samples of human urine; 118
      samples (58%) were positive (with levels >125 pg x l(-1) of urine). CONCLUSIONS:
      When calculated to a concentration of creatinine in urine, the average was 391 pg
      x g(-1), the median was 127 pg x g(-1), and the percentile (90%) was 585 pg x g(
      1). The aflatoxin M1 levels ranged from 19 to 19 219 pg x g(-1) of creatinine.

PMID- 15584621
TI  - [Thromboelastography in liver transplantation, a comparison with conventional
      laboratory tests].
AB  - BACKGROUND: The aim of our study was to compare the results of conventional tests
      and thromboelastography during liver transplantation and to determine their
      importance for blood loss. METHODS AND RESULTS: Thromboelastography and
      conventional laboratory tests were undertaken in 25 patients at the end of the
      anhepatic phase. Transfusion requirements correlated significantly only with
      prothrombin time and reaction time, R. These two tests likewise correlated
      significantly one with the other. CONCLUSIONS: Lowered plasma levels of
      coagulation factors of the prothrombin complex influenced the blood losses in our
      patients. While not replacing conventional tests, thromboelastography can serve
      as an additional test for monitoring acute changes in hemostasis.

PMID- 15584622
TI  - [Proteasome inhibitors--new option in the treatment of tumor diseases].
AB  - Chemotherapy itself probably will not substantially improve the prognosis of
      cancer patients in the future. Therefore new methods are needed one of the
      promising option is the direct interference with intracellular metabolism--"the
      targeted therapy". Proteasome inhibitors are the example of this new approach and
      bortezomib is the first agent in this class, which enters clinical trials. We
      summarize theoretical background and the first clinical experiences with this
      drug.

PMID- 15584623
TI  - [Weil's disease: a severe case with respiratory insufficiency].
AB  - In the patient case (man, age 25) with suspected leptospirosis, indication for
      polymerase chain reaction (PCR) are supposed and procedures suitable for taking
      biological material are recommended. In the presented case of leptospirosis,
      serious conditions were accompanied by high fever, chills, hepatorenal failure,
      meningitis, pneumonia, increased bleeding time and further symptoms are
      described. Introduction of the molecular biological methods (PCR) enables to
      determine leptospiroses diagnosis even in the early phase of the disease, when
      the antibodies are not yet formed. Detection of DNA pathogenic leptospires in the
      PCR method is completed with serological examination by microagglutination-lysis
      (MAL) method for determination of the corresponding serovar that is important
      from therapeutic and epidemiological reasons.

PMID- 15584624
TI  - [Case reports of patients with a marker chromosome].
AB  - Small, usually supernumerary chromosomes, denoted as marker chromosomes or
      markers, can be represented by various phenotypic expression, that depends on
      their origin and extent. Our article presents results of molecular cytogenetic
      analysis (FISH) of 34 patients with identified marker chromosome. In 21 cases a
      marker derived from acrocentric chromosome was identified, in 9 cases markers of
      gonosomal origin [der(X), der(Y)], and in 4 patients markers of some other
      chromosomes (5, 17, 18) were proved. The most frequent marker was that
      originating from chromosome 15 (8 cases). Two patients with different phenotype,
      markedly influenced by the extent of pseudoizodicentric chromosome 15 are
      described. In accordance with hitherto presented data, presence of supernumerary
      copies of the critical region PWACR (it is the partial trisomy, resp. tetrasomy
      15q11-q13) in majority of cases brings about serious affection described as
      syndrome of the inverted duplication of chromosome 15. The most typical symptoms
      are psychomotoric retardation, hypotony, neurological symptoms and autistic
      features. The article stresses the importance of FISH method in the prenatal
      examination of marker chromosomes.

PMID- 15584625
TI  - [ABC of smoking cessation. Use of simple advice and behavioural support].
AB  - The most effective methods of helping smokers to quit smoking combine
      pharmacotherapy (such as nicotine or bupropion) with advice and behavioural
      support. These two components contribute about equally to the success of the
      intervention. Doctors and other health professionals should therefore be familiar
      with what these strategies offer, encourage smokers to use them, and be able at
      least to provide simple advice and behavioural support to smokers. They also need
      to be familiar with other sources of support, such as written materials,
      telephone help-lines, and strategies for preventing relapses. This article
      focuses on non-pharmacological interventions.

PMID- 15584626
TI  - Premenstrual asthma: emphasis on drug therapy options.
AB  - Premenstrual asthma is quite common, affecting up to 40% of women. Some studies
      suggest exacerbations of asthma requiring emergency department visits or
      hospitalizations are more common in the perimenstrual phase. Several drug
      treatment modalities for premenstrual asthma have been evaluated. Drug therapies
      that may be beneficial include leukotriene receptor antagonists, long acting
      inhaled beta2 agonists, progesterone, estradiol, and gonadotropin-releasing
      hormone (GnRH) analogs. Further double-blind, randomized, placebo-controlled
      studies are required before the optimal drug therapy for premenstrual asthma is
      established.

PMID- 15584627
TI  - The association of anxiety with asthma among a sample of asthmatics in Ile-Ife
      Osun State Nigeria.
AB  - BACKGROUND: The association between asthma and anxiety has been a subject of
      various studies in developed countries, but there has been little work done in
      this area in developing countries. The goal of this study is to determine whether
      asthmatics are more anxious than orthopaedic patients and healthy individuals.
      METHOD: Fifty consecutive asthmatics were assessed. All completed a
      sociodemographic questionnaire, the General Health Questionnaire (GHQ--30) and
      the State Trait Anxiety Inventory (STAI--1 and 2). Healthy individuals (30) and
      orthopaedic patients (30) were also recruited as controls; they also completed
      the GHQ and the STAI--1 and 2. RESULTS: No significant difference was found in
      the sociodemographic variables such as age, sex, occupation, and marital status.
      The asthmatics had a mean GHQ score of 4.2 (SD+/-4.6) while orthopaedic and
      healthy control groups scored 1.6 (SD+/-1.8) and 2 (SD+/- 1.8), respectively.
      There was a significant difference in the mean score of the index population
      (Asthmatics) and the comparison groups (F=7.09, DF=2/107, P=0.004). With GHQ,
      cutoff point of > or =5.34% of asthmatics scored above 5 while 10% and 13.3% of
      the orthopaedic patients and healthy controls each scored > or =5. A significant
      difference was obtained in the mean scores on the STAI--1 questionnaire (F=4.6,
      DF=2/107, P=.012) indicating state anxiety whereas there was no significant
      difference on the STAI-2 questionnaire (F= 1.2, DF=2/107, P=0.31). CONCLUSION:
      Although asthmatics have higher anxiety compared to controls, this is not an
      inherent problem or trait among them.

PMID- 15584628
TI  - Postural changes in nasal and pulmonary resistance in subjects with asthma.
AB  - INTRODUCTION: Subjects with asthma frequently have nasal symptoms and complain of
      orthopnoea but airflow resistance is usually only assessed during oral breathing
      and while seated. METHOD: We have used a forced oscillation technique to measure
      total respiratory resistance (Rrs) at 6Hz during mouth breathing (Rrs,mo) and
      during nose breathing (Rrs,na) in the sitting and supine postures; resistance of
      the nasal airway (Rnaw) was estimated as Rrs,na--Rrs,mo. Forced oscillations were
      applied during normal tidal breathing and the mid-tidal lung volume (MTLV) was
      determined for each breathing route and posture. SUBJECTS: Three groups of
      subjects were studied: 10 normal subjects without lung or nasal disease (N; five
      males, mean age 33.5 [range 23-58] years, mean FEV1 105%pred, FEV1/VC 86%); seven
      subjects with asthma alone (A; four males, 40.3 [23-57] years, mean FEV1 66%pred,
      FEV1/VC 74%); 10 asthmatic subjects with nasal obstructive symptoms (AN; six
      males, 62.8 [38-80] years, mean FEV1 56%pred, FEV1/VC 75%). RESULTS: In all three
      groups of subjects, mean Rrs,mo and Rrs,na were higher in the supine than sitting
      posture. In normal subjects the increase in supine Rrs,mo was associated with a
      0.6 liter fall in MTLV. In asthma supine Rrs,mo increased despite a much smaller
      fall in MTLV; supine increases in Rrs,na were particularly large in presence of
      nasal disease. DISCUSSION: Values of airflow resistance are 2-3 times higher in
      both normal and asthmatic subjects when breathing via the nose and supine than
      under normal laboratory conditions of oral breathing and seated.

PMID- 15584629
TI  - The association between hospital readmission and insurance provider among adults
      with asthma.
AB  - CONTEXT: Asthma is ranked as the ninth most common chronic condition in the U.S.,
      and its annual direct costs from hospital services alone are estimated at $3.1
      billion. Hospitalization rates due to asthma reveal several disparities and may
      be attributed to recent changes in the healthcare delivery system, including the
      penetration of managed care. OBJECTIVE: To examine the relationship between 7-day
      hospital readmission and insurance provider among adults with asthma. DDESIGN: A
      retrospective cohort study that included patients aged 18-64 with a principal
      diagnosis of asthma, who were discharged from acute nonfederal hospitals in New
      Jersey between 1 January 1993 and 31 December 1996. In the absence of unique
      patient identifiers, a linkage system was used to match subsequent readmissions
      for the same patient to the first admission. MMAIN OUTCOME MEASURE: Seven-day
      readmission. RESULTS: Results showed a significantly increased risk of 7-day
      readmission for managed care patients as compared to indemnity patients (OR=
      1.67, 1.10-2.53). Shorter lengths of stay were associated with greater odds of
      readmission (LOS=0: OR=5.17, 2.49-10.75, LOS=1: OR=2.30, 1.30-4.07). CONCLUSIONS:
      Managed care patients have shorter lengths of stay as compared to indemnity
      patients, which leads to an increased risk of returning to the hospital within a
      short period of time. In trying to provide cost-effective patient care, we may be
      discharging patients prematurely.

PMID- 15584630
TI  - Treatment of chronic cough in children with montelukast,a leukotriene receptor
      antagonist.
AB  - Twenty-two children (13 boys and 9 girls) with chronic cough were treated with
      the leukotriene receptor antagonist montelukast (Singulair tbl. 5 mg)
      administered once daily for four weeks. In 14 children (68%), the cough ceased
      during the third week of treatment. Children responding to montelukast were found
      to have higher blood levels of eosinophil cationic protein (S-ECP) in the
      pretreatment blood sample than children with no response (responders 14.88+/
      2.651 microg/l versus nonresponders 6.62+/-0.948 microg/l; p<0.01). Blood S-ECP
      levels remained higher also in the post-treatment blood sample in responders
      (10.55+/-1.631 microg/l) compared to nonresponders (6.13+/-0.937 microg/l;
      p<0.05). The difference is statistically significant. There were also differences
      in absolute eosinophil blood count and IgE blood levels between the two groups in
      the pretreatment blood sample. Using 24-hour pH-metry, two children not
      responding to therapy were subsequently diagnosed to have gastroesophageal
      reflux. Judging from the results, one might deduct that patients with chronic
      cough who have increased levels of serum ECP and absolute eosinophil blood counts
      are likely to benefit from treatment with montelukast.

PMID- 15584631
TI  - Effect of mouthpiece washing on aerosol performance of CFC-free Ventolin.
AB  - The prescribing information for chlorofluorocarbon (CFC)-free salbutamol metered
      dose inhalers carries a strongly-worded instruction to wash the mouthpiece
      weekly, but patients rarely carry this out. This study investigated the effect of
      washing/not washing the mouthpiece on CFC-free Ventolin aerosol performance.
      Twelve CFC-free Ventolin inhalers were actuated two puffs four times/day, and
      assessed by unit dose sampler and cascade impactor on Days 1, 7, 8, 14, 15, 21,
      and 22 ("throughlife," i.e., over the entire content of the inhaler). The
      mouthpieces of six inhalers were washed after the last actuation on Days 7, 14,
      and 21. A single priming maneuver, as recommended by the manufacturer, was
      sufficient for fine particle mass. There were no significant through-life
      differences in delivered dose between washed and unwashed inhalers. Without
      washing, fine particle mass fell from 47 microg to 33 microg (Friedman p=0.002).
      Fine particle mass increased significantly after washing (median change + 11.2
      microg, p=0.019 cf. unwashed). Large particle mass showed no significant through
      life trend for washed or unwashed inhalers, but was significantly reduced after
      washing (p=0.04 cf. unwashed). This study shows a progressive through-life
      reduction in fine particle mass from CFC-free Ventolin inhalers, which is
      prevented by weekly mouthpiece washing. However, in view of the steep
      bronchodilator dose-response curve for salbutamol, further studies are needed to
      determine whether such device care is clinically necessary.

PMID- 15584632
TI  - Enhancing validity: what counts as an asthma attack?
AB  - BACKGROUND: Major epidemiological studies in asthma use the question: "How many
      attacks of asthma have you had in the last 12 months?" We set out to study what
      constitutes an asthma attack from the perspective of people with asthma. We also
      examined concordance between qualitative responses and standard quantitative
      measures of this question. METHODS: Individuals aged 18 to 70 years who sought
      care for asthma at Emergency Departments in an Australian central city, a
      suburban and a regional hospital were recruited. Sixty two (43 women and 19 men)
      participants were interviewed in depth. All interviews were taped, transcribed
      and thematically analyzed. Demographic data and responses to respiratory health
      data were also collected. FINDINGS: Widely varying responses to the question,
      "How many attacks of asthma have you had in the last 12 months?" were found in
      the quantitative data set. Comparison of quantitative and qualitative data sets
      showed good agreement between these two responses (intraclass correlation 0.66).
      People defined asthma attacks as "major" and "minor," as determined by the degree
      of personal control they were able to exercise. A strongly unifying description
      of a severe attack was that it was "out of control." Patient's recognized that
      upper respiratory tract infections commonly triggered major attacks.
      INTERPRETATION: A commonly asked question about the number of asthma attacks in
      the past year needs refinement in order to enhance validity. Asthma action plans
      should use the words "out of control" when defining a severe attack of asthma.

PMID- 15584633
TI  - Teaching school teachers to recognize respiratory distress in asthmatic children.
AB  - OBJECTIVE: To demonstrate that school teachers can be taught to recognize
      respiratory distress in asthmatic children. METHODOLOGY: Forty-five school
      teachers received a one-hour educational session on childhood asthma. Each
      education session consisted of two portions, video footage of asthmatic children
      exhibiting respiratory distress and didactic. Pre- and posttests on general
      asthma knowledge, signs of respiratory distress on video footage and comfort
      level with asthma knowledge and medications were administered. RESULTS: General
      asthma knowledge median scores increased significantly, pre = 60% correct, post =
      70% (p < 0.0001). The ability to visually recognize respiratory distress also
      significantly improved (pre-median = 66.7% correct, post = 88.9% [p < 0.0001]).
      Teachers' comfort level with asthma knowledge and medications improved.
      CONCLUSIONS: Using video footage, school teachers can be taught to visually
      recognize respiratory distress in asthmatic children. Improvement in visual
      recognition of respiratory distress was greater than improvement in didactic
      asthma information.

PMID- 15584634
TI  - An evaluation of standardizing target ventilation for eucapnic voluntary
      hyperventilation using FEV1.
AB  - Athletes are required to provide objective documentation of exercise-induced
      bronchoconstriction (EIB) to use beta2-agonists during Olympic competition. A
      positive response to bronchial provocation by eucapnic voluntary hyperventilation
      (EVH) is considered acceptable confirmation of EIB. Thirty times forced
      expiratory volume in the first second (FEV1) is recommended as EVH target
      ventilation (TV), an intensity intended to estimate 85% of maximal voluntary
      ventilation (MVV). There is a paucity of data examining the accuracy of
      predicting MVV from FEV1 in elite athletes. The purpose of this study was to
      evaluate the efficacy of 30 x FEV1 as standardized EVH TV. Maximal minute
      ventilation during exercise (VEmax) and pulmonary function of 78 elite winter
      athletes (25 males, 53 females; 25 EIB positive, 53 normal) were analyzed
      retrospectively. Adequacy and variability of the equation was ascertained by
      examining the ratio of EVH TV (30 x FEV1) to VEmax. VEmax was 99+/-11% of
      predicted MVV (35 x FEV1) and was positively related (r=0.85, p < or = 0.05). TV
      was 88+/-9% of VEmax (range: 64-109). For elite athletes, the high variability in
      30 x FEV1 to standardize TV for EVH may result in under-diagnosis for low-end
      outliers. Since VEmax of elite endurance athletes is typically known (via maximal
      aerobic testing) we recommend 85% VEmax as a more accurate and reliable method to
      establish EVH TV for this group; if VEmax is not available, then 85% of measured
      MVV may be used.

PMID- 15584635
TI  - Exhaled nitric oxide in relation to the clinical features of childhood asthma.
AB  - BACKGROUND: Exhaled nitric oxide (ENO) has been shown to be a noninvasive marker
      of eosinophilic inflammation in asthmatic children. Few studies have evaluated
      the relationship between ENO levels and the clinical features of children with
      asthma. The aim of this study was to examine children attending a routine asthma
      clinic and evaluate the relationship between ENO levels and clinical parameters
      including decision making. METHODS: Asthmatic children (n= 133, aged 5 to 14
      years) attending a hospital asthma clinic were studied. ENO levels were measured
      and compared between subgroups of subjects according to recent symptoms, asthma
      control and treatment, and the clinician's decision (blinded to ENO levels)
      regarding further management. RESULTS: ENO levels (median [IQR] ppb) were
      significantly elevated in children who had recent symptoms compared to those
      without recent symptoms (14.6 [6.5 to 45.3] vs. 6.0 [3.2 to 17.4], difference
      between medians 8.6, 95% confidence interval [CI] (1.8 to 13.9, p=0.004). ENO
      levels differed significantly between the controlled and uncontrolled subgroups
      (8.5 [4.2 to 26.4] vs. 26.4 [5.0 to 62.0], difference between medians 17.9, 95%
      CI 0.1 to 22.8, p=0.03) and between the three treatment decision subgroups (up,
      down, or unchanged; p < 0.001). CONCLUSIONS: ENO levels are strongly related to
      the clinical features of childhood asthma and the clinical decision making
      process. To fully evaluate the role of ENO in the clinical management of asthma,
      this "proof of concept" study paves the way for prospective randomized trials of
      the inclusion of ENO levels in the decision making process in childhood asthma.

PMID- 15584636
TI  - Fractional exhaled nitric oxide (FENO), lung function and airway
      hyperresponsiveness in naive atopic asthmatic children.
AB  - BACKGROUND: Measurement of fractional exhaled nitric oxide (FENO) is a
      noninvasive, simple, well-tolerated, and reproducible marker of airway
      inflammation. Asthmatic children with normal respiratory function could be
      affected by airway inflammation. The aim of this study was to assess the
      correlation between FENO and bronchial hyperesponsiveness (BHR) to methacholine,
      and between FENO and lung function in atopic children with intermittent asthma.
      METHODS: Thirty-seven children (21 male), aged 7.2-14.4 years (median: 10.9
      years), suffering from mild intermittent atopic asthma with a physician-diagnosed
      history of wheezing and/or chest tightness were studied. None had taken anti
      asthmatic therapy for at least three months before the study. No child had
      symptoms of respiratory tract infection in the month before the study. All
      subjects underwent FENO measurement, pulmonary function testing and the
      methacholine provocation tests. RESULTS: The mean percentages of FEV1 and FEF25
      27 were 91.9+/-10.5 and 88.3+/-11.8, respectively. The mean FENO was 62.2+/-39.2
      ppb and PC20 methacholine was 0.93 mg/ml+/-0.54. Significant correlations were
      identified between FENO and FEV1 (p<0.0059, r=0.468) and between FENO and FEF25
      75 (p<0.0098, r=0.439). There was no correlation between FENO and logPC20
      (p=0.14). CONCLUSIONS: A single FENO measurement is probably of scarce prognostic
      and predictive value and it is not surprising to find discordance with BHR. We
      suggest that FENO measurement could represent a good marker of airway
      inflammation also in naive atopic children with intermittent asthma. Repeated
      measurements over time are probably necessary to understand better the clinical
      implications of the data obtained in this study.

PMID- 15584637
TI  - [Role of dietary fibers in the nutritional management of chronic renal failure].
AB  - During the past few decades, considerable attention has been given to the impact
      of nutrition on kidney disease. Although most dietary attempts to treat chronic
      renal failure (CRF) and to decrease uremia recommend a protein restriction,
      another dietetic approach, based on dietary fibers (DF), can lead to the same
      urea-lowering effect by increasing urea-nitrogen (N) excretion in stool with a
      concomitant decrease of the total N quantity excreted in urine. In fact, feeding
      DF results in a greater rate of urea N transfer from blood to large bowel, where
      it will be hydrolyzed by bacterial ureases before subsequent microflora
      metabolism and proliferation. Because elevated concentration of serum urea N have
      been associated with adverse clinical symptoms of CRF, these results suggested a
      possible usefulness of combining DF with a low protein diet to increase N
      excretion via the fecal route. These results have been shown in animal models of
      experimental renal failure and in CRF patients. Further investigations in this
      population of patients are currently in progress to study whether DF may be
      beneficial on CRF progression and on CRF terminal stage tolerance. A part of this
      work is financed by the French Society of Nephrology.

PMID- 15584638
TI  - [Pregnancy and hemodialysis].
AB  - Pregnancy is a rare occurrence in patients on chronic hemodialysis (CHD). The
      rate of successful pregnancies amounts to almost 60%, thanks to modifications of
      the dialysis schedule and a specifically adapted obstetrical and neonatal
      management. We report on seven pregnancies occurring between 1995 and 2001 in six
      women with a mean age of 32 years (22-39 years), on HD for a mean period of 36
      months (12-96 months). Maternal and fetal complications, and the long-term
      outcome of mothers and children are reported, and the collaborative approaches
      adopted by obstetrician, pediatrician and nephrologist are discussed. The
      frequency and length of HD was systematically increased. One patient chose to
      terminate her pregnancy at 20 weeks of gestation. The mean gestational age for
      the six other pregnancies was 31 weeks (24-34 weeks) with an average weight at
      birth of 1495 g (660-1920 g). One neonate born at 24 weeks died 2 days following
      delivery. One patient was treated with uterine artery embolization for post
      partum haemorrhage. Pediatric evaluation of the five children, who were followed
      up for a period ranging between 2.5 to 5.5 years, showed a good long-term
      outcome. In conclusion, pregnancy needs not be counterindicated or systematically
      terminated in patients on CHD, particularly if transplantation is not possible,
      if the patient refuses it, or if she is relatively old and there is a long
      waiting period before transplantation.

PMID- 15584639
TI  - [Phototherapy and hemodialysis pruritus].
AB  - The renal failure-related pruritus is frequent (10-30%) and this frequency
      increases in dialysed patients (60-80%). Its physiopathology remains badly known.
      The prurit is variable in intensity and surface. It predominates on the forehead,
      the back and the forearms. The skin is normal on it presents non specific
      lesions. The best treatment would be the renal graft. When it can't be done,
      phototherapy represents a good therapeutic alternative. We report the experience
      of our patients from December 1993 to January 2002. The patients could benefit
      from a steady treatment and be well followed-up. The mean age of our patients was
      51 years with a masculine predominance (12 men to 7 women). The mean duration of
      hemodialysis was 3 years and the one of prurit was 10 months. Between December
      1993 and January 2001, UVB phototherapy with a spectrum was used in 14 cases.
      After this period a phototherapy with a narrow spectrum was used. The mean dose
      was 2 Joules with a number of sessions. Eventually, the total body irradiation
      with UVB was the most regularly effective therapy of the hemodialysed prurit. It
      allows an important reduction, which is a significant result in comparison with
      UVA irradiation.

PMID- 15584640
TI  - [Acute renal failure and 2,8-dihydroxyadeninuria].
AB  - We report the case of a 65 year old man, with a history of recurrent
      urolithiasis, who was referred for an acute renal failure. Investigations deny
      obstructive or glomerular involvement. 2,8-Dihydroxyadeninuria was diagnosed with
      the help of crystalluria. This rare metabolic disease is due to a deficiency of
      adenine phosphoribosyltransferase, a purine salvage enzyme. Allopurinol, a low
      purine diet and high fluid intake made possible the nearly entire regression of
      renal failure.

PMID- 15584641
TI  - Short-term effect of folic acid supplementation in renal transplant recipients
      and chronic kidney disease patients with comparable renal function impairment.
AB  - Recent evidence suggested that the efficacy of folic acid supplementation in
      reducing plasma total homocysteine (Hcy) concentration might be similar in renal
      transplant recipients (RTR) and chronic kidney disease (CKD) patients with a
      comparable degree of reduction of renal function. However, a direct comparison of
      the response to high dose folic acid supplementation between renal transplant
      recipients and CKD patients has never been made. Therefore, the goal of this
      study was to evaluate the response to folic acid (5 mg/day) supplementation in 15
      stable renal transplant recipients with evidence of chronic allograft
      nephropathy, and in 15 CKD (stage 3) patients matched for age, sex and renal
      function living in the area of Skopje, Macedonia. After 12 weeks of folic acid
      supplementation, plasma total Hcy concentrations were significantly reduced in
      the two groups. Percent reduction of plasma total Hcy levels was nearly identical
      in the two groups (25.7% vs 24.5%, p = NS). These results confirm previous
      findings regarding the efficacy of folic acid therapy given separately to either
      renal transplant recipients or CKD patients, and extend them to a direct
      confirmation of identical efficacy.

PMID- 15584642
TI  - [Medical research: Europe's stake].

PMID- 15584643
TI  - [Gabapentin (Neurontin) and cancer pain: a pilot study].
AB  - Gabapentin (GBP) is a new antiepileptic agent with an original spectrum of
      activity. Its mechanism of action has not yet been fully elucidated but appears
      not to involve binding to GABA receptors despite being a structural analogue of
      GABA and is distinct from tricyclic antidepressants (TCAs). It has been shown to
      modulate high threshold calcium currents in brain neurons. As some other
      anticonvulsants, GBP has been recently proposed for the treatment of noncancer
      neuropathic pain like diabetic neuropathy and post herpetic neuralgia (double
      blind studies with placebo). We prospectively followed 20 cancer patients with
      advanced disease suffering from neuropathic pain. All were already treated for
      their pain syndrome. We started with 300 mg of GBP given orally in order to reach
      a dose of 900 mg on D3. All coanalgesics were stopped before entering the study.
      The only relevant side effect due to GBP was somnolence, otherwise time limited.
      GBP treatment was associated with a decrease of opioids doses in 9 patients and a
      decrease of VAS for pain intensity in all cases. Furthermore, the need of rescue
      doses decreased in all cases but 2. GBP appears to be one of the most effective
      drugs for the treatment of neuropathic pain. It is well tolerated and its
      effectiveness appears shortly after its administration. A synergistic action with
      opioids is suggested. Despite the small number of patients, our study suggests
      that GBP could be a treatment of neuropathic pain in cancer. Comparative trials
      should be performed with other neuropathic pain drugs including TCAs and
      antiepileptic drugs, especially carbamazepine.

PMID- 15584644
TI  - [The five-word test in memory deficiency].
AB  - The 5-Word test is a bedside memory test with free and cued selective
      recollection. Here, we evaluated its reliability Belgian French speakers. Five
      groups were studied : normal subjects, depressive patients, patients with AD,
      patients with vascular dementia and 47 patients for a validation of a logistic
      model. The results of the 5-Word test with the MMSE, both values were included as
      variables in a logistic regression model. The probability of diagnosis of AD and
      dementia can be calculated and used prospectively for assessment of new cases in
      a validation study. The importance of the study of free and cued response during
      immediate and delayed recall was assessed by variance analysis in 4 groups. A
      third order interaction (p < 0.001) was observed between the normal and AD
      groups, the normal and vascular dementia (VD) groups and between AD and VD
      groups. With this initial model, 98% of the 62 normal subjects and the 57
      patients with AD were correctly classified (p < 0.001). For AD diagnosis at the
      onset, the sensitivity of the MMSE is increased when it is associated with the 5
      Word. This low-tech bedside method associating the 5-Word test and MMSE has a
      good specificity for the diagnosis of AD. It is very useful for screening a
      population of patients at the onset of cognitive and memory deficiency and for
      selecting the patients requiring an examination at a memory clinic.

PMID- 15584645
TI  - [Psychological repercussions of parental divorce on child].
AB  - The parental divorce is an experience with traumatic risk for child. The child's
      adaptation depends on many factors : his age, his personality and his parent's
      one, his life context. Those aspects are developed. As the parental separation
      moves forward, the symptoms that appear in the child are essentially linked to
      anxiety and feeling of loss. None of these is specific to the parental separation
      and are, most of the time, temporary. Divorce has to be considered as a factor of
      vulnerability rather than one precise etiology. The conflicts' persistence
      between parents seems to be the factor the most important in the worst influence
      for child's adaptation.

PMID- 15584646
TI  - [Neurodevelopment of extremely low birthweight infants born in Erasmus Hospital
      between 1992 and 2001].
AB  - Survival of extremely low birth weight infants has dramatically improved in the
      last decade of the twentieth century. The objective of our study was to evaluate
      the neurological evolution of the surviving infants because frequent motor,
      sensitive and psychological disturbances are related. Prospective, longitudinal
      study in a population of newborns, nursed in our neonatal intensive care unit and
      born between 1992 and 2001 with less than 1.000 g and/or less than 28 weeks of
      gestational age (GA). Neurological assessment of outcome was made using the
      neurodevelopmental score (O.M.S. 1988) at 6, 9, 12, 18, 24 and 36 months.
      Neurological follow-up every year and neuropsychological testing at 3, 5 and 8
      years. Only children with at least 2 years of follow-up were included. The
      children were grouped in 3 categories: M (major neurological handicap), m (minor
      neurological handicap), N (normal neurological outcome). To evaluate the
      evolution with time, we compared the results from the first period (1992 to 1996)
      to the second part of this decade (1997 to 2001). Mortality fell from 38% (27/70)
      in the first period (1992-1996) to 18% (8/44) in the second one (1997-2001) (p =
      0.02) including neonates of less than 25 weeks GA. Neurodevelopmental status
      improved and severe brain lesions decreased (25% with intraventricular
      haemorrhage III & IV and cystic periventricular leukomalacia versus 6% in the
      second period) (p = 0.017). Major handicap fell from 26% (9/34) to 16% (5/31) and
      normal neurological evolution raised from 15% (5/34) to 48% (15/31) (p = 0.013).
      With the survival of newborns less than 28 weeks, the severe ocular complications
      increased: 6% (5/79). In conclusion, mortality and quality of life have
      significantly improved in the past 10 years in our service. Severe brain lesions
      have decreased under a better multifactorial management. Nevertheless when the
      gestational age of the surviving babies diminishes, ocular sequelae increase. We
      still think that prematurity remains a burden for the child, his family and the
      society.

PMID- 15584647
TI  - [Ezetimibe (Ezetrol): the statins' partner].
AB  - Ezetimibe is a new cholesterol absorption inhibitor that selectively inhibits
      dietary and biliary cholesterol absorption from the intestine. This drug inhibits
      cholesterol absorption without affecting the absorption of triglycerides, biliary
      salts and fat-soluble vitamins. Inhibition of cholesterol absorption using
      ezetimibe 10 mg/day alone resulted in substantial reductions of plasma LDL-C
      concentrations (approximately 18%). Coadministration of ezetimibe 10 mg/day with
      statins 10 mg/day showed LDL lowering comparable to or greater than that of the
      highest dose of the respective statin alone. Combination therapy of ezetimibe
      with statins helped more patients in achieving their target LDL-C goal. Ezetimibe
      in coadministration with statins or alone had also favourable effects on
      triglycerides and HDL. In clinical studies, ezetimibe alone or coadministered
      with a statin was shown to have a safety profile (asymptomatic mild increases in
      aminotransferase levels, without evidence of rhabdomyolysis) similar to placebo
      or to the statin alone. Large clinical studies on clinical endpoints are in
      progress.

PMID- 15584648
TI  - [Combined middle and inner ear abnormality: report of a case].
AB  - Congenital anomalies of the middle ear associated to anomalies of the inner ear
      are rarely described. Our case displays a malformation due to an association of
      congenital absence of the round window and aplasia of the semi-circular canals,
      causing conductive hearing loss. First diagnosis was a congenital atresia
      isolated of the round window, related to a previous surgical exploration. We
      tried a novel technique designed to restore the function of the round window.
      Labyrinthine anomalies prevented a good outcome. This kind of malformative
      association could be due to the complexity of early genetic control of ear
      development. Attentive analysis of imaging should be performed before middle ear
      surgery to determine the presence of inner ear anomalies which are quite frequent
      and which would limit its usefulness.

PMID- 15584649
TI  - [Control and evaluation of euthanasia. First report of the Federal Commission to
      the Legislative Chambers for the period from September 22, 2002 to December 31,
      2003].

PMID- 15584650
TI  - [Jean-Henri Meibomius and the physiologic anatomy of the male urogenital system].

PMID- 15584651
TI  - [Prognosis after acute coronary syndrome. Lack of difference according to the
      sex].
AB  - Acute coronary syndromes (ACS) represent a continuum from unstable angina to non
      ST-elevation myocardial infarction. ACS is the preferred diagnostic term for non
      transmural myocardial infarction. The different forms of ACS share a common
      anatomic substrate consisting of atherosclerotic plaque rupture or erosion, with
      variable degrees of thrombus formation and compromised blood flow to viable
      myocardium. Patients with ACS have a heterogeneous profile of short- and mid-term
      adverse outcomes and require a tailored approach. Recent major advances in the
      management of ACS have emphasized the importance of earlier identification of
      higher-risk patients, whose outcome might be improved by aggressive
      revascularization. However, during the past several years, numerous studies have
      shown a significant difference in the prognosis of women and men with ACS. Some
      reports have concluded that women have a worse prognosis than men after
      thrombolytic therapy and/or coronary angioplasty with stenting for myocardial
      reperfusion. The aim of our retrospective study was to determine sex differences
      in outcomes after early percutaneous intervention (PCI) in high-risk patients
      with acute coronary syndromes (ACS). A total of 694 consecutive patients (151
      women with 233 treated lesions and 543 men with 850 treated lesions) were
      included. Enrollments were limited to ACS patients judged to be at high risk
      [unstable angina/non ST-elevation myocardial infarction with recurrent
      ischemia/dynamic ST segment changes (53.6% vs 52.4%) or post-infarction unstable
      angina (46.4% vs 47.6%)] who underwent PCI within 24 hours of admission if the
      coronary anatomy was deemed suitable. The two groups were well matched for
      clinical and lesion characteristics, except that the women, as in other studies,
      were older (67.9 +/- 11.3 vs 62.3 +/- 12.3 years) and had a higher prevalence of
      hypertension. All the lesions were treated by stent implantation, and
      glycoprotein IIb/IIIa inhibitors were used similarly in the two sexes (27.1% of
      women, 30.5% of men). The success rates were similar (94% and 93.7%), with a
      similar incidence of in-hospital MACE (4% vs 3.8%, p = 0.56). After a mean follow
      up of 564 +/- 294 days, the two groups had similar rates of mortality (2% vs
      3.2%), myocardial infarction (6.7% vs 7.1%) and repeated revascularization (7.2%
      vs 8.3%). The respective event-free survival rates were 88 +/- 60.3% and 83 +/-
      0.3% at 1 year and 87% vs 78 +/- 0.2% at 2 years (p = 0.58). Previous studies
      have shown increased morbidity and mortality associated with recurrent ischemia
      and myocardial infarction in women after acute revascularization for ACS. Our
      study confirms that aggressive revascularization offers a comparable survival
      benefit in the two sexes. Women with ACS who are at high risk derive the same
      benefit as men from early angioplasty and coronary stenting of the culprit
      lesion, with satisfactory in-hospital and mid-term outcomes.

PMID- 15584652
TI  - [Cardiovascular risk].
AB  - Diseases involving an atherosclerotic process, such as coronary heart disease,
      stroke, heart failure and peripheral arterial disease, are by far the leading
      cause of death and disability among both men and women of all ethnic groups. The
      Framingham study and many other epidemiologic investigations have significantly
      improved the identification of persons at risk and factors amenable to preventive
      measures. Multivariate risk profiles have been devised in numerous studies with
      the aim of facilitating global risk assessment. The SCORE project offers a direct
      estimation of the overall 10-year cardiovascular risk in high-risk and low-risk
      regions of Europe. Guidelines are offered to improve cardiovascular prevention.
      Management of arterial hypertension is a major element. Many persons currently
      classified as normotensive will become candidates for blood pressure reduction
      because their cardiovascular risk is high.

PMID- 15584653
TI  - [Immunohistochemical expression of PTEN antigen: a new tool for diagnosis of
      early endometrial neoplasia].
AB  - We examined immunohistochemical PTEN protein expression in endometrial samples
      obtained from perimenopausal women with uterine bleeding in order to diagnose
      early endometrial neoplasia. Paraffin sections of endometrial samples (biopsies,
      endometrium resection, hysterectomy) were reviewed and tested for
      immunocytochemical PTEN expression by epithelial cells. Immunohistochemical
      studies were performed with the Ventana Benchmark device and the immunoperoxidase
      technique with monoclonal anti-PTEN (6H2.1/Cascade Biosciences). We studied 45
      samples of proliferative endometria, 42 samples of atypical hyperplasia
      (neoplasia), and 55 samples of endometrial carcinomas (30 endometrioid, 5 serous
      papillary, 10 clear cell, 5 adenosquamous, and 5 MMMT). A strong positive PTEN
      immunoreaction was observed in all 45 normal proliferative endometria, 2/30
      endometrioid carcinomas, and 23/25 non endometrioid carcinomas. In contrast, PTEN
      immunoexpression was negative or weak in 40/42 atypical hyperplasia and 28/30
      endometrioid carcinomas. Negative or weak PTEN expression correlated with
      endometrial neoplasia (atypical proliferation) (p < 0.001). Thus (i) PTEN
      immunoexpression in endometrial paraffin sections is a new diagnostic tool,
      distinguishing PTEN-positive cyclic abnormal monoclonal proliferative endometrium
      (anovulatory, non atypical, simple and complex hyperplasia) from PTEN-negative
      (or decreased) endometrial neoplasia, and especially early endometrial neoplasia
      (atypical simple and complex hyperplasia, in situ carcinoma, superficial
      carcinoma with focal invasion). (ii) Given the lack of reproducibility of
      histological identification of atypical (precancerous invasive) and non atypical
      (precancerous non invasive) endometrial hyperplasia, the new criteria (PTEN
      negative crowded glands, gland/stroma ratio > 55%, nuclear pleomorphism, in areas
      > 1 mm) recently proposed to diagnose early endometrial neoplasia appear to be
      clinically relevant.

PMID- 15584654
TI  - [Telephone in medical practice].
AB  - The telephone is increasingly used as a means of communications between patients
      and physicians. It has several advantages (mainly for the patient), but also
      several drawbacks (mainly perceived by the physician). Specific training in
      telephone interview techniques, including possible pitfalls, should be offered to
      all medical students.

PMID- 15584655
TI  - [25 years review of vascular microsurgery evaluation--perspectives].
AB  - Free-tissue transfer has become an accepted method for reconstructing complex
      surgical defects. We review 25 years' experience of this approach. In France,
      microsurgery was first performed in 1974. I myself constructed 839 consecutive
      free flaps in 821 patients during a 25-year period. Here we distinguish between
      two different indications, namely malignant and benign lesions. In oncology, the
      patient recovers good quality of life even if the prognosis is poor. In contrast,
      the transplant offers permanent cure for patients with benign lesions.
      Microvascular anastomoses were constructed with separated stitches (90% of
      anastomoses); end-to-end anastomoses were preferred (85%). Manual suture with
      thread is the best technique. Post-operative flap monitoring included clinical
      observation, Doppler sonography, thermic probing, and endoscopy. The overall
      success rate of free flap reconstruction was 95.5%. In cancer patients, surviving
      flaps resulted in wound healing and did not delay post-operative irradiation or
      chemotherapy. The incidence of major complications (death 0.36%, necrosis 4.5%)
      and minor post operative complications (27.1%) was acceptable. The mean hospital
      stay was 20 days. Careful selection of the transplants yielded good reliability.
      Six donor sites were sufficient to reconstruct the majority of defects. Teaching
      of microsurgery is one of our main preoccupations. This is an indispensable
      technique in all fields of reconstruction. Rigorous training is necessary and
      much time must be spent before reaching a high level of reliability.

PMID- 15584656
TI  - [People living in Paris, dead during the August 2003 heatwave, and examined in
      Medicolegal Institute].
AB  - Of the 452 people who died at home in Paris between August 1 and 31, 2003, and
      were transported to the Medicolegal Institute (IML), 92% died between August 1st
      and 20th. This study is based on investigations carried out at the discovery of
      the body, and on the results of medical examinations performed at IML. Half the
      study population were over 80 years old, and 88% lived alone, half of them in top
      story single rooms. More than 70% had medical antecedents, cardiovascular
      disorders and psychological disorders. Three-quarters had forerunner symptoms.
      The extreme vulnerability of these people makes them the prime target for
      prevention.

PMID- 15584657
TI  - [Necrotizing soft tissue infections: role of the localization for the antibiotic
      management].
AB  - Necrotizing soft tissue infections (NSTI) are infrequent but life-threatening,
      and require prompt empirical antibiotic therapy. Current nosologic
      classifications have limited value because the criteria used are imprecise and
      their bacteriological specificity is uncertain. The aim of this study was to
      describe the bacterial flora and its antibiotic sensitivity in a cohort of
      patients with NSTI, and to derive guidelines for the choice of antimicrobial
      chemotherapy. This prospective study involved 120 patients. Aerobic and anaerobic
      bacteriological samples were taken from infected soft tissues. The species
      distribution and susceptibility of the isolates to various antibiotic (ATB)
      combinations were analyzed. The data were analyzed according to the type
      (cellulitis versus myonecrosis) and anatomical location of NSTI (abdomen and
      perineum; uterine cervix; limbs). The chi-square test was used to analyze
      qualitative variables, and Student's t test was used for quantitative variables.
      A total of 232 samples yielded bacterial isolates (122 aerobic, 110 anaerobic).
      The species distribution of anaerobes did not differ according to the nature of
      the involved tissue or the anatomic location. Gram-negative aerobes were more
      frequently isolated from abdominal, perineal and limb sites than from the cervix
      (p<0.05), while gram-positive aerobes showed the reverse distribution (p<0.05).
      Metronidazole was more effective than clindamycin on cervical isolates (95% vs
      88%, p=0.0093). Among the broad-spectrum antibiotics tested, imipenem/cilastatin
      and piperacillin/tazobactam were equally effective against the different groups
      of bacteria (94% vs 88%, p=0.14), and were clearly more active than the other
      antibiotics (p<0.05), whatever the site of isolation, the bacterial species, and
      the type of NSTI. The five antibiotics tested showed similar efficacy against
      cervical isolates. These results suggest that the choice of antibiotic therapy
      for NSTI should depend on the anatomical site of involvement rather than the
      nature of the infection. For abdominal, perineal and limb NSTI, we recommend
      first-line treatment with a betalactam-inhibitor combination
      (piperacillin/tazobactam or ticarcillin/clavulanate) plus an agent active on gram
      negative species (aminoglycoside or fluoroquinolone). For cervical NSTI, we
      recommend penicillin G/metronidazole, or amoxicillin/clavulanic acid.

PMID- 15584658
TI  - [Sickle cell disease in childhood in 2004].
AB  - Sickle cell disease is a genetic autosomal recessive disease of hemoglobin. The
      disease results from a mutation of the sixth codon of the beta-globin gene, which
      induces the synthesis of an abnormal hemoglobin called hemoglobin S (HbS). The
      polymerisation of deoxy HbS molecules causes a chronic hemolytic anemia and vaso
      occlusive phenomena. The disease affects mainly people from West Indies and Sub
      Saharan Africa. Due to recent movements of these populations over the past years,
      sickle cell disease has spread across all continents. Painful crises, severe
      infections such as septicemia, meningitis, osteomyelytis, acute anemia episodes,
      and severe vaso-occlusive events, mainly neurological, are the most frequent
      complications affecting children. Recent progresses in the care of patients have
      deeply modified the prognosis. The mean life expectancy of patients is now above
      40 years. The conventional treatment includes antibiotics and immunizations,
      analgesics, and blood transfusion. The effects of chronic blood transfusion,
      hydroxyurea and bone marrow transplantation are the subject of current
      comparative evaluations.

PMID- 15584659
TI  - [Emergencies in adults with sickle cell disease].
AB  - Sickle cell disease is an inherited disease characterized by the presence of an
      abnormal haemoglobin. It is the more prevalent genetic disease at birth in Ile-de
      France area. Sickle cell disease can be complicated by acute vaso-occlusive
      crisis, chronic visceral involvement related to ischemic process, and infectious
      complications. In adults, acute vaso-occlusive crisis is the major clinical
      problem prompting admission to hospital and the main cause of death. It mainly
      manifests by osteoarticular pain and acute chest syndrome and can be complicated
      by multiorgan failure. Acute vaso-occlusive crisis can be also manifested by
      priapism, ischemic or haemorrhagic stroke, or abdominal pain. The main treatment
      of severe acute vaso-occlusive crisis is based on transfusion.

PMID- 15584660
TI  - [Organizational principles of prophylactic medical examination quaility control
      in the Armed Forces].
AB  - The authors suggested new organizational and methodical approaches to a
      prophylactic medical examination (PME) and its quality control. There were
      distinguished and analyzed organizational and medical aspects of the profound
      medical examination (PrME) and dynamic observation (DO). The process of planning,
      interaction and analysis of PME results as well as the importance of the medical
      and-statistical indices as indicators of PrME and DO quality were described. The
      analysis showed the substantial role of medical standards in the PME. Being in
      fact peculiar models of the PrME and DO for doctors, they serve as medical and
      methodical documents. The authors offered the standards of the PME of servicemen
      and reserve soldiers (retirees), the principles of their use, which allow taking
      into consideration individual peculiarities of each person examined.

PMID- 15584661
TI  - ["Trained and initiative staff and stable financing are the main conditions of
      effective and accessible medical treatment"].

PMID- 15584662
TI  - [Consultive-and-diagnostic help to servicemen and their families' members in the
      territorial system of medical support].

PMID- 15584663
TI  - [The development of specialized ambulant diagnosis by the experience of the 52nd
      Consultative-and-diagnostic Center of the Russian Federation Ministry of
      Defense].

PMID- 15584664
TI  - [The historical aspects of the integration of the military hospitals and
      polyclinics].

PMID- 15584665
TI  - [Leadership training in the military polyclinic institutions in view of reforming
      the military health services].

PMID- 15584666
TI  - [The damaging factors of emergency situations and models of their formation].

PMID- 15584667
TI  - [Endovideosurgery of gunshot wounds].
AB  - The paper deals with the opportunities of using endovideosurgery in local armed
      conflicts. There were worked out methods and technique of endovideosurgical
      operations in case of gunshot wounds of a chest, a belly and lower limbs. Due to
      a low level of traumatism and high efficiency the method promotes the decrease of
      the number of complications, early activation of the insured servicemen during
      the post-operation period, the reduction in time of treatment and rehabilitation
      and can be recommended at the initial stage of medical evacuation.

PMID- 15584668
TI  - [The peculiarities of diagnosis and medical treatment of the elderly and the old
      in ambulant conditions].

PMID- 15584669
TI  - [The organization of gynecologic treatment by the 52nd Consultative-and
      diagnostic Center of RF MD].

PMID- 15584670
TI  - [The ways of the increase in effectiveness of diagnosis and expertise of the drug
      abuse].

PMID- 15584671
TI  - [The meningococcal infection on Navy: modern clinical-and-epidemiological
      aspects].
AB  - The article presents the own data about modern clinical-and-epidemiological
      peculiarities of a meningococcal infection on Navy for 20 consecutive years (1982
      2002) based on the analysis of the annual reports of fleet medical services and
      the inspection of 275 centers of a meningococcal infection in military troops.
      The centers with the single generalized form of a meningococcal infection
      prevailed. The centers with the number of people from 10 to 40 men amounted to
      82%. The frequency of the meningococcal defeat of the people in the centers
      varied from 25% to 37% with the main role of meningococcae A. In the structure of
      a meningococcal infection the generalized forms amounted to 16%, located forms-
      25%, carriers--59%. In all regions the major form of the display of epidemic
      process in military collectives was seasonal sick rate. The article proved the
      electoral approach to the character and volume of curative-and-preventive
      measures.

PMID- 15584672
TI  - [Psychology of a personality and the influence of fighting stress].

PMID- 15584673
TI  - [E.I. Smirnov and the Military-and-medical Academy (devoted to the 100th
      anniversary of E.I. Smirnov)].

PMID- 15584674
TI  - The financial return on education programs.
AB  - Preparing data that demonstrate the financial return on education or training
      programs is not an easy task. It is complex, given the usual program costs. It is
      further complicated by the fact that qualitative data are often important in
      service organizations (e.g., health care). Finding a way to express the value of
      programs using both quantitative and qualitative data serves educators well
      because it helps to build the total and whole picture of the programs and their
      impact. Developing standard formats such as templates for both quantitative and
      qualitative data will help strengthen the position of education within the
      organization and will aid in the demonstration of the financial and human value
      of the training and education programs.

PMID- 15584675
TI  - Minimally invasive total hip arthroplasty: what is it all about?

PMID- 15584676
TI  - Creating staff-friendly continuing education: the Tidbits and Niblets program.

PMID- 15584677
TI  - Surviving the nursing shortage: developing a nursing orientation program to
      prepare and retain intensive care unit nurses.
AB  - The shortage of nurses has reached crisis proportions around the world. In
      response to a critical shortage of qualified neonatal intensive care nurses, one
      institution developed an educational program so comprehensive that they were able
      to increase their nursing staff by 20% and staff the neonatal intensive care unit
      with well-prepared and proficient nurses. This strategy has also resulted in high
      retention rates, a decrease in overtime, and a relatively low error rate by new
      nurses.

PMID- 15584678
TI  - Teaching cognitive rehearsal as a shield for lateral violence: an intervention
      for newly licensed nurses.
AB  - BACKGROUND: Recent literature defines lateral violence as nurses covertly or
      overtly directing their dissatisfaction inward toward each other, toward
      themselves, and toward those less powerful than themselves. Newly licensed nurses
      are an identified group that is vulnerable to lateral violence during their
      socialization to nursing practice. The use of cognitive rehearsal, an applied
      cognitive-behavioral technique, was used as an intervention and the theoretical
      underpinning for this study. METHOD: Twenty-six newly licensed nurses hired by a
      large acute care tertiary hospital in Boston, Massachusetts, participated in an
      exploratory descriptive study. They were taught about lateral violence in nursing
      practice and the use of cognitive rehearsal techniques as a shield from the
      negative effects of lateral violence on learning and socialization. Small
      laminated cueing cards with written visual cues for the appropriate responses to
      the most common forms of lateral violence were provided. One year later,
      videotaped focus groups designed to collect qualitative data about the applied
      intervention were conducted. RESULTS: Twenty-six newly licensed nurses in three
      different focus groups were videotaped responding to six open-ended questions
      designed to elicit information on their experience with lateral violence, use of
      cognitive rehearsal as an intervention, and the overall socialization process.
      CONCLUSIONS: Knowledge of lateral violence in nursing appeared to allow newly
      licensed nurses to depersonalize it, thus allowing them to ask questions and
      continue to learn. The learned cognitive responses helped them confront the
      lateral violence offender. Confrontation was described as difficult but resulted
      in the resolution of the lateral violence behavior. Overall, the retention rate
      in this study population was positively affected.

PMID- 15584679
TI  - Increasing the linguistic competence of the nurse with limited English
      proficiency.
AB  - Teaching linguistic competence to nursing students educated in the United States
      but whose families are recent immigrants is a difficult task for nurse educators.
      Although students may easily learn the mechanics of a new language, the cultural
      differences must also be addressed. In the face of the current nursing shortage,
      it is critically important that strategies to improve linguistic competence be
      incorporated into curricular efforts. This article describes integrated skills
      reinforcement as one academic strategy to improve reading, speaking, listening,
      and writing skills. Suggestions are made for incorporating and evaluating these
      techniques.

PMID- 15584680
TI  - Teaming with students and a Sacred Cow Contest to make changes in nursing
      practice.
AB  - Many current nursing traditions and practices were developed over time by nurses
      who used a trial and error method of research. Nursing has passed along these
      practices through nursing education programs and in the policies and procedures
      established by hospitals. Do these practices have sound scientific principles
      behind their use, or are they just traditions that are difficult to change? This
      article explores the experience of one educator trying to make changes in the
      attitudes of students toward research and suggests how this process can be
      applied in the day-to-day practice of staff nurses.

PMID- 15584681
TI  - Replacing dermal constituents lost through aging with dermal fillers.

PMID- 15584682
TI  - Surgical margins of excision for basal cell carcinoma and squamous cell
      carcinoma.
AB  - In excising basal and squamous cell carcinomata, the surgical margin that is wide
      enough to completely remove the tumor an acceptable percentage of the time and
      narrow enough to minimize removal of excessive normal tissue must be selected.
      This task can be reliably accomplished with comprehensive knowledge of factors
      that affect subclinical tumor extension such as tumor appearance, diameter,
      histology, location, treatment status, and, in the case of squamous cell
      carcinoma, vertical invasion depth and involvement of subcutaneous fat.
      Information regarding these factors along with specific recommendations about
      excisional margins for basal cell and squamous cell carcinomata is presented.

PMID- 15584683
TI  - Topical treatment strategies for non-melanoma skin cancer and precursor lesions.
AB  - The ability to manage non-melanoma skin cancers and pre-malignant lesions with
      topical pharmacologic agents is highly compelling. This article examines
      currently available products and discusses their emerging roles and limitations.
      These include fluorouracil, diclofenac sodium, imiquimod, and photodynamic
      therapy.

PMID- 15584684
TI  - Mohs micrographic surgery pearls.
AB  - Mohs micrographic surgery has evolved over the last 60 years from fixed-tissue
      chemosurgery with secondary intention healing to fresh-tissue surgical excision
      utilizing advanced histotechnology and reconstructive techniques. This evolution
      has occurred while preserving the fundamental characteristics of Mohs surgery:
      microscopically controlled tumor excision by one surgeon acting as pathologists
      to ensure complete tumor extirpation while maximally conserving tissue.
      Refinements, modifications, and clinical pearls will be outlined that uphold
      these tenets and enhance the quality of patient care.

PMID- 15584685
TI  - Simple things that make a difference in nasal reconstruction.
AB  - The nose is the most common location for nonmelanoma skin cancer. As a result,
      nasal reconstruction is a frequent challenge for Mohs surgeons. The esthetic
      outcome of each nasal repair can be improved by replacing nasal skin with the
      most similar match, restoring the intricate three-dimensional structure of the
      nose and applying the principle of cosmetic subunits. This article will present
      techniques and helpful hints, which are useful during nasal reconstruction to
      improve the selected repair and enhance the final result.

PMID- 15584686
TI  - Perioperative care of the surgical patient.
AB  - Efficient care of the surgical patient necessitates attention to key elements of
      preoperative patient preparation prior to the day of surgery, a standardized
      approach to patient monitoring and education on the day of surgery, and careful
      postoperative monitoring. Patient education is fundamental to all phases of
      surgical management so that patient expectations and concerns are practically
      addressed. Quality assurance endeavors must also be integrated into these
      preioperative phases so that optimal care of the surgical patient is ensured.

PMID- 15584687
TI  - Service excellence in dermatology.
AB  - Service excellence is attainable but requires leadership and hard work. It is
      important for the physician leader to understand that perceived service
      excellence is complex and multifaceted. The physician who combines outstanding
      diagnostic and technical skills, an office run with efficient processes, a
      pleasing environment, carefully chosen amenities, and personnel who behave and
      communicate exceptionally will truly have a practice in demand. Our customers-
      patients, family members, referring physicians--are the judges and predictors of
      our success.

PMID- 15584688
TI  - Role of the surface in luminescent processes.

PMID- 15584689
TI  - Chemical reactions of C(1) compounds in near-critical and supercritical water.

PMID- 15584690
TI  - Synthetic preparation of N-methyl-alpha-amino acids.

PMID- 15584691
TI  - Recent developments in the synthesis and structure of organosilanols.

PMID- 15584692
TI  - Biomolecule--mercury interactions: modalities of DNA base--mercury binding
      mechanisms. Remediation strategies.

PMID- 15584693
TI  - Bioorganometallic chemistry of ferrocene.

PMID- 15584694
TI  - Carbohydrate biosensors.

PMID- 15584695
TI  - Chitosan chemistry and pharmaceutical perspectives.

PMID- 15584696
TI  - Beta-strand mimetics.

PMID- 15584697
TI  - Asymmetric fluorination, trifluoromethylation, and perfluoroalkylation reactions.

PMID- 15584698
TI  - Controlled ring-opening polymerization of lactide and glycolide.

PMID- 15584699
TI  - Synthetic methods for azaheterocyclic phosphonates and their biological activity.

PMID- 15584700
TI  - Iron-catalyzed reactions in organic synthesis.

PMID- 15584701
TI  - Organoselenium and organotellurium compounds: toxicology and pharmacology.

PMID- 15584702
TI  - Molecule-based photonically switched half-adder.
AB  - A molecule-based binary half-adder with optical inputs and outputs has been
      demonstrated. The half-adder consists of two photochromic organic molecules in
      solution and a third-harmonic-generating crystal. One substance acts as an AND
      Boolean logic gate and the other as an XOR gate. Inputs are laser pulses at 1064
      or 532 nm that initiate photoisomerization reactions. Outputs are the optical
      absorbance of a fullerene radical anion (AND gate) and fluorescence of a
      porphyrin (XOR gate). The system carries out binary addition based on the laser
      input pulses. Half-adders in combination are capable of carrying out all
      mathematical operations necessary for digital computing.

PMID- 15584703
TI  - Methyl group dynamics as a probe of the protein dynamical transition.
AB  - Hydrated proteins undergo a dynamical transition around 200 K from glasslike to
      liquidlike motion. Molecular dynamics simulations have been used to study the
      temperature dependence of the dynamics of ribonuclease A in the hydrated crystal,
      a model dehydrated powder, and aqueous solution. Changes in the dynamics
      accompanying the transition throughout the protein have been quantified in terms
      of the mean-squared fluctuations (MSFs) of methyl hydrogen atoms on the 100 ps
      time scale. In solution at 300 K the MSFs span a broad distribution, consistent
      with NMR relaxation measurements. The MSF distribution in the hydrated crystal at
      300 K is qualitatively similar to the solution result, except for a slight shift
      to lower values, and dehydration results in a dramatic shift of the MSFs to lower
      values. As the temperature is lowered, the whole distribution of methyl group
      fluctuations in the hydrated crystal shifts to lower values. Most of the methyl
      groups in the hydrated protein display a nonlinear temperature dependence with a
      dynamical transition at approximately 200 K, but most methyl groups do not
      undergo a transition in the dehydrated protein. We conclude that the dynamical
      transition occurs throughout most of the protein and that solvent is required for
      the transition.

PMID- 15584704
TI  - Persulfated molecular umbrellas as anti-HIV and anti-HSV agents.
AB  - A series of persulfated molecular umbrellas have been synthesized from
      putrescine, spermidine, spermine, lysine, and cholic acid (1a, 2a, 3a, 4a, and
      5a) and their anti-HIV and anti-HSV activities determined. Despite it size, the
      most active of these conjugates (5a) was able to cross phospholipid bilayers made
      from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphatidylglycerol (POPG). The unique combination of anti
      viral activity, an ability to cross hydrophobic barriers, a lack of cytotoxicity,
      and a simple three-step synthesis from biogenic starting material suggests that
      5a and related conjugates may be exploitable as a novel class of anti-viral
      agents for systemic and topical applications.

PMID- 15584705
TI  - TiCp2Cl-catalyzed living radical polymerization of styrene initiated by oxirane
      radical ring opening.
AB  - Epoxides and paramagnetic early transition metal complexes are introduced as two
      new classes of initiators and catalysts, respectively, for living radical
      polymerizations. Thus, Ti(III)Cp2Cl synthesized in situ from the reduction of
      TiCp2Cl2 with Zn catalyzes the radical ring opening of oxiranes to initiate the
      radical polymerization of styrene. A linear dependence of molecular weight on
      conversion, low polydispersity, and reinitiation of the polymerization in the
      presence of fresh monomer indicates that the polymerization is living and that it
      most likely occurs by the reversible endcapping of the macroradical with Ti(III).
      Moreover, epoxides provide convenient access to alcohol chain ends, suitable for
      further transformations.

PMID- 15584706
TI  - Two-pump-one-probe femtosecond studies of Ni(II) porphyrins excited states.
AB  - Dual excited states of nickel(II) meso-tetra(4-sulfonatophenyl)porphyrin (NiTPPS)
      and nickel(II) meso-tetraphenylporphyrin (NiTPP) have been investigated by two
      pump-one-probe transient absorption spectrometry. By dual excited states, we mean
      molecular entities that have absorbed two photons to generate molecular states
      with electronic excitation in two distinct regions of metalloporphyrin. Two
      successive pulses of 400 and 550 nm were used for excitation. The first pulse
      (400 nm) produced an S2 state of the porphyrin pi-system, which deactivated to
      give rise to an S1 state and subsequently produce a metal-centered (d,d) state.
      The second (550 nm) pulse selectively targeted an S0 --> S1 transition of those
      molecules having an excited metal center and was delivered to the sample
      approximately 40 ps after the first excitation event. At this time, the ground
      state of the tetrapyrrole pi-system was already regenerated and the excitation
      was localized at the metal center. The kinetic profiles of the NiTPPS transients
      in DMSO revealed biexponential decays with time constants of 0.6 and 4 ps.
      Photoexcitation of NiTPP in toluene and NiTPPS in water resulted in similar
      behavior. A mechanism for the Ni(II) porphyrin dual excited state deactivation
      involving the formation of an intramolecular charge transfer state has been
      proposed.

PMID- 15584707
TI  - Sizable concentration-dependent frequency shifts in solution NMR using sensitive
      probes.
AB  - With the growing use of high fields and ultrasensitive probes, radiation damping
      emerges as a significant feedback interaction in modern solution NMR. Motivated
      by recent observations of mysterious concentration-dependent frequency shifts,
      experiments carried out on a cryoprobe at 600 MHz have revealed a time-averaged
      frequency shift of up to +83/-81 Hz. The sizable frequency shifts arise from
      deviations in the phase of the radiation damping field from perfect orthogonality
      relative to the net transverse magnetization. The frequency shift is shown to
      depend on the longitudinal magnetization and probe tuning conditions through
      experiments and numerical simulations. Such unexpected shifts in the solvent
      precession frequency provide a physical explanation for the empirical practice of
      adjusting the irradiation frequency of the saturating B1 field in solvent
      presaturation to achieve optimal suppression. Additional applications of the
      radiation damping induced frequency shift to solvent suppression and NMR
      methodology are discussed.

PMID- 15584708
TI  - Hybrid microgels photoresponsive in the near-infrared spectral range.
AB  - We report for the first time a photothermally responsive composite material based
      on polymer microgel particles doped with gold nanorods. We used the dependence of
      the longitudinal surface plasmon of the gold nanorods on their aspect ratio to
      synthesize nanoparticles with strong absorption in the near-IR spectral range (in
      the "water window"). The nanoparticles were incorporated in the interior of
      temperature-responsive poly(N-isopropylacrylamide-acrylic acid) microgels. Upon
      irradiation at lambda = 810 nm, hybrid microgel particles doped with Au nanorods
      underwent a strong deswelling phase transition. These photothermally responsive
      microgels can be used to carry and release small molecules (e.g., small protein
      molecules and drugs).

PMID- 15584709
TI  - Small molecule transcription factor mimic.
AB  - Regulation of gene expression by transcription factors touches many aspects of
      eukaryotic biology, and its systematic, external control by organic molecules
      represents a challenge in chemistry. Here we report the design of a completely
      organic, nonpeptidic compound that mimics a transcription factor. The design
      takes advantage of the specific DNA-binding affinity of a hairpin polyamide
      molecule and the ability of wrenchnolol to bind to the Sur-2 subunit of human
      mediator complex. The hybrid compound of these two molecules activates
      transcription of a reporter gene in vitro in a promoter-dependent manner through
      simultaneous contacts with DNA and Sur-2. Our results indicate that it is
      possible to generate a transcription factor out of nonpeptidic components.

PMID- 15584710
TI  - A three-component Mannich-type reaction for selective tyrosine bioconjugation.
AB  - A new selective bioconjugation reaction is described for the modification of
      tyrosine residues on protein substrates. The reaction uses imines formed in situ
      from aldehydes and electron-rich anilines to modify phenolic side chains through
      a Mannich-type electrophilic aromatic substitution pathway. The reaction takes
      place under mild pH and temperature conditions and can modify protein substrates
      at concentrations as low as 20 muM. Using an efficient fluorescence-based assay,
      we demonstrated the reaction using a number of aldehydes and protein targets.
      Importantly, proteins lacking surface-accessible tyrosines remained unmodified.
      It was also demonstrated that enzymatic activity is preserved under the mild
      reaction conditions. This strategy represents one of the first carbon-carbon bond
      forming reactions for protein modification and provides an important complement
      to more commonly used lysine- and cysteine-based methods.

PMID- 15584711
TI  - Artificial ion channel formed by cucurbit[n]uril derivatives with a carbonyl
      group fringed portal reminiscent of the selectivity filter of K+ channels.
AB  - Novel artificial ion channels (1 and 2) based on CB[n] (n = 6 and 5,
      respectively) synthetic receptors with carbonyl-fringed portals (diameter 3.9 and
      2.4 A, respectively) can transport proton and alkali metal ions across a lipid
      membrane with ion selectivity. Fluorometric experiments using large unilamellar
      vesicles showed that 1 mediates proton transport across the membranes, which can
      be blocked by a neurotransmitter, acetylcholine, reminiscent of the blocking of
      the K+ channels by polyamines. The alkali metal ion transport activity of 1
      follows the order of Li+ > Cs+ approximately Rb+ > K+ > Na+, which is opposite to
      the binding affinity of CB[6] toward alkali metal ions. On the other hand, the
      transport activity of 2 follows the order of Li+ > Na+, which is also opposite to
      the binding affinity of 2 toward these metal ions, but virtually no transport was
      observed for K+, Rb+, and Cs+. It is presumably because the carbonyl-fringed
      portal size of 2 (diameter 2.4 A) is smaller than the diameters of these alkali
      metal ions. To determine the transport mechanism, voltage-clamp experiments on
      planar bilayer lipid membranes were carried out. The experiments showed that a
      single-channel current of 1 for Cs+ transport is approximately 5 pA, which
      corresponds to an ion flux of approximately 3 x 107 ions/s. These results are
      consistent with an ion channel mechanism. Not only the structural resemblance to
      the selectivity filter of K+ channels but also the remarkable ion selectivity
      makes this model system unique.

PMID- 15584712
TI  - Axially polar columnar phase made of polycatenar bent-shaped molecules.
AB  - The polycatenar bent-shaped molecules are able to form columnar phases with
      column stratum built of few molecules, arranged in coplanar or conelike geometry.
      In the latter case, the phase becomes axially polar, with electric spontaneous
      polarization reorientable in the electric field by flipping the cone axis. The
      phase is antiferroelectric; in the plane perpendicular to columns, the
      ferroelectric hexagonal order exists, but the columns are broken along the z
      direction and the polarization direction alternates between the blocks.

PMID- 15584713
TI  - MD simulations of spontaneous membrane protein/detergent micelle formation.
AB  - The in vitro study of membrane proteins for the purpose of physicochemical
      analysis or structure determination often relies upon successful reconstitution
      into detergent micelles. Moreover, a number of biological processes such as
      membrane protein folding and transport rely on lipid interactions which may
      resemble the micellar environment. Little is known about the structures of these
      micelles or the processes which lead to their formation. We therefore present two
      50 ns all-atom molecular dynamics simulations of spontaneous
      dodecylphosphocholine micelle formation around representatives of the two major
      families of membrane proteins, a small beta-barrel protein, OmpA, and a model
      alpha-helical protein, glycophorin A. Despite differences in protein
      architecture, we highlight common mechanistic pathways in micelle formation,
      which are consistent with experimental studies. We characterize the exponential
      kinetics of detergent-protein adsorption and suggest a simple model which may
      explain the aggregation process. We also compare the results with 25 and 50 ns
      simulations of preformed micelles containing the same proteins. We confirm that
      the end structures of the self-assembled micelles are similar to those from their
      preformed counterparts, with each micelle presenting a bilayerlike environment to
      the enclosed protein.

PMID- 15584714
TI  - Nanosensors based on responsive polymer brushes and gold nanoparticle enhanced
      transmission surface plasmon resonance spectroscopy.
AB  - Swelling (and shrinking) of poly(2-vinylpyridine), P2VP, polymer brushes, caused
      by pH changes, could be readily monitored by transmission surface plasmon
      resonance, T-SPR, spectroscopy. Gold nanoparticles attached to the P2VP polymer
      brushes dramatically enhanced the pH-induced shift in the T-SPR absorption
      spectra. (A 50 nm shift of the absorption maximum of the T-SPR spectrum of the
      supporting gold nanoislands was observed upon changing the pH from 5.0 to 2.0,
      corresponding to a swelling of the polymer brushes from 8.1 +/- 0.7 to 24.0 +/-
      2.0 nm. Same shift in the opposite direction was observed upon changing the pH
      from 2.0 to 5.0.)

PMID- 15584715
TI  - Photoinduced desorption of sulfur from gold nanoparticles loaded on metal oxide
      surfaces.
AB  - We now report photoinduced sulfur desorption from the surfaces of Au
      nanoparticles loaded on metal oxides. This reaction occurs in water at ordinary
      temperature and pressure. Nanometer-sized Au particles have been formed on the
      surfaces of various metal oxides by deposition-precipitation (Au/oxides).
      Elemental sulfur (S8) is selectively adsorbed on the Au nanoparticle surfaces of
      Au/oxides in an atomic state at a coverage of (theta) </= 1/3 and in both atomic
      and molecular states at theta > 1/3. Irradiation (lambdaex > 300 nm) of the
      sulfur adsorbed Au/anatase TiO2 in water has led to reductive desorption of the
      sulfurs at room temperature. Electrochemical measurements using Au/oxides
      indicate that the driving force for this reaction is the photoinduced upward
      shift of Fermi energy of the metal oxide-supported Au nanoprticles. This study
      will open up a novel and wide application of heterogeneous photocatalysis for
      thermal catalysts.

PMID- 15584716
TI  - Porphyrin nanotubes by ionic self-assembly.
AB  - Porphyrin nanotubes are made by ionic self-assembly of two oppositely charged
      synthetic porphyrin molecules. The diameter of the nanotubes can be altered by
      modifying the structure of one of the porphyrin tectons. The nanotubes are
      photocatalytically active, mechanically responsive to light, and are composed of
      J-aggregates that exhibit resonance light scattering.

PMID- 15584717
TI  - Photoinduced electron transfer reactivity of aza[60]fullerene: three discrete
      functionalization pathways with a single substrate.
AB  - Azafullerenium carbocation, C59N+, shows photoinduced electron transfer (PET)
      reactivity toward benzyltrimethylsilane. The reaction between (C59N)2 and
      benzyltrimethylsilane gives three different aza[60]fullerene monoadducts
      depending on the reaction conditions used.

PMID- 15584718
TI  - Shape-tunable polymer nodules grown from liposomes via ring-opening metathesis
      polymerization.
AB  - A new inisurf (acting as surfactant and initiator) molecule for ring-opening
      metathesis polymerization (ROMP) was synthesized and used in aqueous solution in
      order to control the size and shape of polymer nodules grown from liposomes.
      Nodules were observed to grow in size with conversion of monomer, and depending
      on the monomer used, they adopted either a spherical or comet-like shape. Here,
      we investigate polymer production from a liposome surface. We use a hydrophobic
      derivative of the Grubbs catalyst positioned at the liposome surface to allow for
      ROMP of monomers dissolved in the aqueous outer phase. We obtain nodules of
      polymer that can grow up to tens of micrometers, unveiling new efficient
      possibilities of polymerization from a membrane in an aqueous solution.

PMID- 15584719
TI  - Proton transfer at helium temperatures during dioxygen activation by heme
      monooxygenases.
AB  - In the first measurement of enzymatic proton transfer at liquid helium
      temperatures, we examine protonation of the peroxo-ferriheme state of heme
      oxygenase (HO) produced by in situ radiolytic cryoreduction of oxy-HO in H2O and
      D2O solvents at ca. 4 K and above, and compare these findings with analogous
      measurements for oxy-P450cam and for oxy-Mb. Proton transfer in HO occurs at
      helium temperatures in both solvents; it occurs in P450cam at approximately 50 K
      and higher; in Mb it does not occur until T > 170 K. For Mb, this transfer at 180
      K is biphasic, and the majority phase shows a solvent kinetic isotope effect of
      3.8. We discuss these results in the context of the picture of environmentally
      coupled tunneling, which links proton transfer to two classes of protein motions:
      environmental reorganization (lambda in Marcus-like equations) and protein
      fluctuations ("active dynamics"; gating) which modulate the distance of proton
      transfer.

PMID- 15584720
TI  - A phage display system with unnatural amino acids.
AB  - We report a general method to display peptide-containing unnatural amino acids on
      filamentous M13 phage. Five distinct unnatural amino acids were site-specifically
      incorporated at the N-terminal of the M13 phage minor coat protein pIII. Phages
      that contain p-azidophenylalanine can undergo a highly specific azide-alkyne [3 +
      2] cycloaddition reaction with an alkyne-derivatized fluorophore. The
      generalization of phage display to include unnatural amino acids should
      significantly increase the scope of phage display technology.

PMID- 15584721
TI  - A unique catalyst effects the rapid room-temperature cross-coupling of organozinc
      reagents with carboxylic acid fluorides, chlorides, anhydrides, and thioesters.
AB  - We have identified a catalyst capable of effecting the rapid, room-temperature
      cross-coupling between acid fluorides and diorganozinc reagents. The use of acid
      fluorides as electrophilic partners allows this reaction to tolerate epimerizable
      functionality as well as beta leaving groups. The same catalyst is also capable
      of cross-coupling acid chlorides, acyl cyanides, anhydrides, thioesters, and
      pyridyl esters. Noteworthy is the ability of the reaction to successfully
      transfer both groups from the organometalic fragment.

PMID- 15584722
TI  - Observation of a rectangular columnar phase in a DNA-calcium-zwitterionic lipid
      complex.
AB  - In the presence of calcium, DNA and unilamellar liposomes of the zwitterionic
      lipid DPPC form a complex in which DNA strands are embedded between a lamellar
      phase of DPPC. In some complexes, in-plane alignment of the DNA strands occurs,
      where a DNA-DNA interaxial distance can be measured using small-angle X-ray
      scattering. Here we report a higher level of DNA organization, with a rectangular
      columnar phase of DNA identified within this complex structure. This observation
      is important in view of recent interests in creating new synthetic systems at the
      interface of biology.

PMID- 15584723
TI  - The total synthesis of (-)-SNF4435 C and (+)-SNF4435 D.
AB  - The size and positioning of substituents on a tetraene, along with the Woodward
      Hoffmann rules, control the relative stereochemistry at the four adjacent chiral
      centers that are generated in the 8pi/6pi electrocyclization cascade. A
      biomimetic synthesis of (-)-SNF4435 C and (+)-SNF4435 D exploits these steric
      effects and allows confirmation of the predicted absolute stereochemistry of the
      natural products.

PMID- 15584724
TI  - Total synthesis of amphidinolide X.
AB  - A concise total synthesis of the cytotoxic marine natural product amphidinolide X
      (1) is described. A key step of the highly convergent route to this structurally
      rather unusual macrodiolide derivative consists of a newly developed, highly syn
      selective formation of allenol 6 by an iron-catalyzed ring opening reaction of
      the enantioenriched propargyl epoxide 5 (derived from a Sharpless epoxidation)
      with a Grignard reagent. Allenol 6 was then cyclized with the aid of Ag(I) to
      give dihydrofuran 7 containing the (R)-configured quarternary sp3 chiral center
      at C19 of the target. The anti-configured chiral centers at C10 and C11 were
      formed by the palladium-catalyzed, Et2Zn-promoted addition of propargyl mesylate
      12 to the functionalized aldehyde 11. The key fragment coupling at the C13-C14
      bond was achieved by the "9-MeO-9-BBN" variant of the alkyl-Suzuki reaction.
      Finally, the 16-membered macrodiolide ring was formed by a Yamaguchi
      esterification/lactonization strategy.

PMID- 15584725
TI  - Right-handed helical structure of expanded oligo(L-leucine) containing
      [Ru(terpyridine)2]2+ moieties.
AB  - Expanded oligo(l-leucine)s, containing an alternate arrangement of a
      bis(terpyridine)ruthenium(II) moiety and a l-leucine residue, were synthesized
      and characterized by 1H NMR, UV, CD, and electrochemical properties. The
      intensity of CD spectra per ruthenium unit increased with the elongation of the
      peptide chain. 1H NMR analysis of a tetramer indicated the right-handed helical
      structure in acetonitrile.

PMID- 15584726
TI  - Self-assembled electrooptic thin films with remarkably blue-shifted optical
      absorption based on an X-shaped chromophore.
AB  - An "X-shaped" two-dimensional electrooptic (EO) chromophore with extended
      orthogonal conjugation was designed and synthesized. Self-assembled thin films of
      this chromophore were fabricated via layer-by-layer chemisorptive siloxane-based
      self-assembly. The films exhibit a dramatically blue-shifted optical maximum (325
      nm) while maintaining a large EO response (chi33(2) approximately 232 pm/V at
      1064 nm; r33 approximately 43 pm/V at 1550 nm).

PMID- 15584727
TI  - Redox buffering of hypochlorous acid by thiocyanate in physiologic fluids.
AB  - The major antimicrobial products of neutrophilic myeloperoxidase (MPO) in
      physiologic fluids are hypochlorous acid (HOCl) and hypothiocyanite (OSCN-), and
      the former is generally believed to be the killing agent. However, we have
      determined that HOCl oxidizes SCN- in a facile nonenzymic reaction. The observed
      kinetics and computational models substantiate the hypothesis that SCN- serves to
      moderate the potential autotoxicity of HOCl by restricting its lifetime in
      physiologic fluids. Furthermore, the oxidizing equivalents of HOCl are preserved
      in OSCN-, a more discriminate biocide that is not lethal to mammalian cells.

PMID- 15584728
TI  - Gold(I)-catalyzed propargyl Claisen rearrangement.
AB  - Homoallenic alcohols are prepared from propargyl vinyl ethers using a trinuclear
      gold(I)-oxo complex, [(Ph3PAu)3O]BF4, as a catalyst for propargyl Claisen
      rearrangement at room temperature. The gold(I)-catalyzed reaction is effective
      for a diverse collection of propargyl vinyl ethers, including substrates
      containing aryl and alkyl groups at the propargylic position, and hydrogen, aryl,
      and alkyl substituents at the alkyne terminus. Tertiary propargyl vinyl ethers
      can be employed in the reaction, at slightly elevated temperatures, to afford
      tetrasubstituted allenes. Importantly, the rearrangement of 1,2-disubstituted
      vinyl ethers proceeds with excellent diastereoselectivity, and the rearrangement
      of chiral nonracemic propargyl vinyl ethers proceeds with excellent chirality
      transfer to furnish enantioenriched allenes.

PMID- 15584729
TI  - Gamma4-aminoxy peptides as new peptidomimetic foldamers.
AB  - The conformational properties of peptides 1-3 of gamma-aminoxy acids have been
      investigated by using FT-IR, NMR spectroscopy, and X-ray crystallography. Diamide
      1 consisting of unsubstituted gamma-aminoxy acid cannot form intramolecular
      hydrogen bond. A novel gamma N-O turn involving a 10-membered-ring intramolecular
      hydrogen bond between NHi+2 and COi is formed in gamma4-aminoxy peptides 2 and 3.
      Triamides 3 prefers a new helical structure featuring two consecutive gamma N-O
      turns. Therefore, gamma4-aminoxy peptides represent new peptidomimetic foldamers.

PMID- 15584730
TI  - A sonochemical route to single-walled carbon nanotubes under ambient conditions.
AB  - A chemical route to single-walled carbon nanotubes (SWCNTs) under ambient
      conditions has been developed. Silica powder was immersed in a mixture solution
      of ferrocene and p-xylene. After sonication at atmospheric pressure and room
      temperature, we obtained high-purity SWCNTs. Sonochemical effects may lead to
      producing high-purity SWCNTs. The process could be readily generalized to
      synthesize other forms of carbon-based materials, such as fullerenes, multiwalled
      nanotubes, carbon onions, and diamond, in liquid solution under ambient
      conditions.

PMID- 15584731
TI  - In situ chemical aminoacylation with amino acid thioesters linked to a peptide
      nucleic acid.
AB  - tRNA-specific chemical aminoacylation was achieved with nonnatural amino acids. A
      nonnatural amino acid was activated as a thioester derivative, and the latter was
      linked through a spacer to the N-terminal of a 9-mer peptide nucleic acid that is
      complementary to the 3'-terminal region of yeast phenylalanine tRNA. Efficient
      aminoacylation was observed when the amino acid thioester-spacer-PNA conjugate
      was mixed with the tRNA. The PNA-assisted aminoacylation was also successful in
      an Escherichia coli in vitro protein synthesizing system that contained an
      orthogonalized tRNA. The in situ aminoacylation/in vitro translation gave a
      mutant protein in which the nonnatural amino acid was incorporated into the
      position directed by a CGGG 4-base codon/anticodon pair.

PMID- 15584732
TI  - Facile, efficient, and enantiospecific syntheses of 1,1'-N-linked
      pseudodisaccharides as a new class of glycosidase inhibitors.
AB  - This article describes an efficient synthesis of a potent trehalase inhibitor,
      1,1'-N-linked pseudodisaccharide 1 (consisting of two valienamines), in 14 steps
      with an overall yield of 12% and a first synthesis of 2 (consisting of two 2-epi
      valienamines) in 15 steps with an overall yield of 24% from (-)-quinic acid. The
      synthesis involves a stereospecific palladium-catalyzed coupling reaction between
      an allylic amine and an allylic chloride as the crucial step. The acetonide
      blocking groups were shown to be the best hydroxyl protecting groups, compatible
      with the palladium-catalyzed allylic amination reaction that afforded high yields
      of the 1,1'-N-linked pseudodisaccharides with a minimum amount of an elimination
      diene side product.

PMID- 15584733
TI  - Unusually broad substrate tolerance of a heat-stable archaeal sugar
      nucleotidyltransferase for the synthesis of sugar nucleotides.
AB  - Herein, we report the first cloning, recombinant expression, and synthetic
      utility of a sugar nucleotidyltransferase from any archaeal source and
      demonstrate by an electrospray ionization mass spectrometry (ESI-MS)-based assay
      its unusual tolerance of heat, pH, and sugar substrates. The metal-ion-dependent
      enzyme from Pyrococcus furiosus DSM 3638 showed a relatively high degree of
      acceptance of glucose-1-phosphate (Glc1P), mannose-1-phosphate (Man1P), galactose
      1-phosphate (Gal1P), fucose-1-phosphate, glucosamine-1-phosphate, galactosamine-1
      phosphate, and N-acetylglucosamine-1-phosphate with uridine and deoxythymidine
      triphosphate (UTP and dTTP, respectively). The apparent Michaelis constants for
      Glc1P, Man1P, and Gal1P are 13.0 +/- 0.7, 15 +/- 1, and 22 +/- 2 microM,
      respectively, with corresponding turnover numbers of 2.08, 1.65, and 1.32 s(-1),
      respectively. An initial velocity study indicated an ordered bi-bi catalytic
      mechanism for this enzyme. The temperature stability and inherently broad
      substrate tolerance of this archaeal enzyme promise an effective reagent for the
      rapid chemoenzymatic synthesis of a range of natural and unnatural sugar
      nucleotides for in vitro glycosylation studies and highlight the potential of
      archaea as a source of new enzymes for synthesis.

PMID- 15584734
TI  - Photocatalytic oxygenation of anthracenes and olefins with dioxygen via selective
      radical coupling using 9-mesityl-10-methylacridinium ion as an effective electron
      transfer photocatalyst.
AB  - Visible light irradiation of the absorption band of 9-mesityl-10-methylacridinium
      ion (Acr+-Mes) in an O2-saturated acetonitrile (MeCN) solution containing 9,10
      dimethylanthracene results in formation of oxygenation product, i.e.,
      dimethylepidioxyanthracene (Me2An-O2). Anthracene and 9-methylanthracene also
      undergo photocatalytic oxygenation with Acr+-Mes to afford the corresponding
      epidioxyanthracenes under the photoirradiation. In the case of anthracene, the
      further photoirradiation results in formation of anthraquinone as the final six
      electron oxidation product, via 10-hydroxyanthrone, accompanied by generation of
      H2O2. When anthracene is replaced by olefins (tetraphenylethylene and
      tetramethylethylene), the photocatalytic oxygenation of olefins affords the
      corresponding dioxetane, in which the O-O bond is cleaved to yield the
      corresponding ketones. The photocatalytic oxygenation of anthracenes and olefins
      is initiated by photoexcitation of Acr+-Mes, which results in formation of the
      electron-transfer state: Acr*-Mes*+, followed by electron transfer from
      anthracenes and olefins to the Mes*+ moiety together with electron transfer from
      the Acr* moiety to O2. The resulting anthracene and olefin radical cations
      undergo the radical coupling reactions with O2*- to produce the
      epidioxyanthracene (An-O2) and dioxetane, respectively.

PMID- 15584735
TI  - Ligand binding properties of myoglobin reconstituted with iron porphycene:
      unusual O2 binding selectivity against CO binding.
AB  - Sperm whale myoglobin, an oxygen storage hemoprotein, was successfully
      reconstituted with the iron porphycene having two propionates, 2,7-diethyl
      3,6,12,17-tetramethyl-13,16-bis(carboxyethyl)porphycenatoiron. The
      physicochemical properties and ligand bindings of the reconstituted myoglobin
      were investigated. The ferric reconstituted myoglobin shows the remarkable
      stability against acid denaturation and only a low-spin characteristic in its EPR
      spectrum. The Fe(III)/Fe(II) redox potential (-190 mV vs NHE) determined by the
      spectroelectrochemical measurements was much lower than that of the wild-type.
      These results can be attributed to the strong coordination of His93 to the
      porphycene iron, which is induced by the nature of the porphycene ring symmetry.
      The O2 affinity of the ferrous reconstituted myoglobin is 2600-fold higher than
      that of the wild-type, mainly due to the decrease in the O2 dissociation rate,
      whereas the CO affinity is not so significantly enhanced. As a result, the O2
      affinity of the reconstituted myoglobin exceeds its CO affinity (M' = K(CO)/K(O2)
      < 1). The ligand binding studies on H64A mutants support the fact that the slow
      O2 dissociation of the reconstituted myoglobin is primarily caused by the
      stabilization of the Fe-O2 sigma-bonding. The IR spectra for the carbon monoxide
      (CO) complex of the reconstituted myoglobin suggest several structural and/or
      electrostatic conformations of the Fe-C-O bond, but this is not directly
      correlated with the CO dissociation rate. The high O2 affinity and the unique
      characteristics of the myoglobin with the iron porphycene indicate that
      reconstitution with a synthesized heme is a useful method not only to understand
      the physiological function of myoglobin but also to create a tailor-made function
      on the protein.

PMID- 15584736
TI  - Counterion controlled photoisomerization of retinal chromophore models: a
      computational investigation.
AB  - CASPT2//CASSCF photoisomerization path computations have been used to unveil the
      effects of an acetate counterion on the photochemistry of two retinal protonated
      Schiff base (PSB) models: the 2-cis-penta-2,4-dieniminium and the all-trans-epta
      2,4,6-trieniminium cations. Different positions/orientations of the counterion
      have been investigated and related to (i) the spectral tuning and relative
      stability of the S0, S1, and S2 singlet states; (ii) the selection of the
      photochemically relevant excited state; (iii) the control of the radiationless
      decay and photoisomerization rates; and, finally, (iv) the control of the
      photoisomerization stereospecificity. A rationale for the results is given on the
      basis of a simple (electrostatic) qualitative model. We show that the model
      readily explains the computational results providing a qualitative explanation
      for different aspects of the experimentally observed "environment" dependent PSB
      photochemistry. Electrostatic effects likely involved in controlling retinal
      photoisomerization stereoselectivity in the protein are also discussed under the
      light of these results, and clues for a stereocontrolled electrostatically driven
      photochemical process are presented. These computations provide a rational basis
      for the formulation of a mechanistic model for photoisomerization electrostatic
      catalysis.

PMID- 15584737
TI  - Refinement of NMR structures using implicit solvent and advanced sampling
      techniques.
AB  - NMR biomolecular structure calculations exploit simulated annealing methods for
      conformational sampling and require a relatively high level of redundancy in the
      experimental restraints to determine quality three-dimensional structures. Recent
      advances in generalized Born (GB) implicit solvent models should make it possible
      to combine information from both experimental measurements and accurate empirical
      force fields to improve the quality of NMR-derived structures. In this paper, we
      study the influence of implicit solvent on the refinement of protein NMR
      structures and identify an optimal protocol of utilizing these improved force
      fields. To do so, we carry out structure refinement experiments for model
      proteins with published NMR structures using full NMR restraints and subsets of
      them. We also investigate the application of advanced sampling techniques to NMR
      structure refinement. Similar to the observations of Xia et al. (J.Biomol. NMR
      2002, 22, 317-331), we find that the impact of implicit solvent is rather small
      when there is a sufficient number of experimental restraints (such as in the
      final stage of NMR structure determination), whether implicit solvent is used
      throughout the calculation or only in the final refinement step. The application
      of advanced sampling techniques also seems to have minimal impact in this case.
      However, when the experimental data are limited, we demonstrate that refinement
      with implicit solvent can substantially improve the quality of the structures. In
      particular, when combined with an advanced sampling technique, the replica
      exchange (REX) method, near-native structures can be rapidly moved toward the
      native basin. The REX method provides both enhanced sampling and automatic
      selection of the most native-like (lowest energy) structures. An optimal protocol
      based on our studies first generates an ensemble of initial structures that
      maximally satisfy the available experimental data with conventional NMR software
      using a simplified force field and then refines these structures with implicit
      solvent using the REX method. We systematically examine the reliability and
      efficacy of this protocol using four proteins of various sizes ranging from the
      56-residue B1 domain of Streptococcal protein G to the 370-residue Maltose
      binding protein. Significant improvement in the structures was observed in all
      cases when refinement was based on low-redundancy restraint data. The proposed
      protocol is anticipated to be particularly useful in early stages of NMR
      structure determination where a reliable estimate of the native fold from limited
      data can significantly expedite the overall process. This refinement procedure is
      also expected to be useful when redundant experimental data are not readily
      available, such as for large multidomain biomolecules and in solid-state NMR
      structure determination.

PMID- 15584738
TI  - Dispersion interactions enable the self-directed growth of linear alkane
      nanostructures covalently bound to silicon.
AB  - Current interest in methods for controllably adding organic molecules to silicon
      surfaces relates to proposed hybrid silicon-organic devices. It was recently
      shown that a "self-directed" growth process, requiring only limited scanned probe
      intervention, has the potential to permit rapid, parallel production of ordered
      molecular nanostructures on silicon with predefined absolute position, structure,
      composition, and extent of growth. The hybrid organic-silicon structures formed
      are bound by strong covalent interactions. In this work, we use scanning
      tunneling microscopy and density functional theory techniques to show that
      molecule-surface dispersion interactions enable the growth process and play a
      crucial role in the final configurations of the nanostructures.

PMID- 15584739
TI  - Fragmentation of aryl halide pi anion radicals. Bending of the cleaving bond and
      activation vs driving force relationships.
AB  - Recent rate data for very fast cleaving of aryl chloride and bromide anion
      radicals may be accommodated satisfactorily within rate constant versus ArX/ArX*-
      standard potential existing correlations provided the standard potential is
      determined experimentally. Cyclic voltammetry is used for this purpose, taking
      careful account of the electron transfer/fragmentation reaction mixed character
      of the kinetics. The ensuing activation/driving force relationships allow the
      determination of the intrinsic barriers, the magnitude of which are discussed in
      the framework of a new Morse curve model that includes and emphasizes the role of
      bond bending.

PMID- 15584740
TI  - Deoxygenation and other photochemical reactions of aromatic selenoxides.
AB  - Atomic oxygen O(3P) is a potent oxidant that has been well-studied in the gas
      phase. However, exploration of its reactivity in the condensed organic phase has
      been hampered by the lack of an appropriate source. Dibenzothiophene-S-oxide
      (DBTO) and related derivatives have been promoted as photochemical O(3P) sources
      but suffer from low quantum yields. Photolysis of dibenzoselenophene-Se-oxide
      (DBSeO) results in the formation of dibenzoselenophene and oxidized solvent in
      significantly higher quantum yields, ca. 0.1. The oxidation product ratios from
      toluene obtained from the photolysis of dibenzothiophene-S-oxide and the
      corresponding selenoxide are the same, strongly suggesting a common oxidizing
      intermediate, which is taken to be O(3P). An additional product, proposed to be
      the corresponding selenenic ester, is also observed under deoxygenated
      conditions. The photochemistry of diphenyl selenoxide includes a minor portion of
      oxidant-forming deoxygenation, in contrast to previous conclusions (Yamazaki, Y.;
      Tsuchiya, T.; Hasegawa, T. Bull. Chem. Soc. Jpn. 2003, 201-202).

PMID- 15584741
TI  - Ruthenium- and platinum-catalyzed sequential reactions: selective synthesis of
      fused polycyclic compounds from propargylic alcohols and alkenes.
AB  - A simple method for the preparation of fused polycyclic compounds by an
      intramolecular cyclization of propargylic alcohols bearing an alkene moiety at a
      suitable position has been developed, where the presence of both Ru and Pt
      catalysts promotes a sequence of catalytic cycles in the same medium. This
      sequential system can be applied to an intermolecular reaction between a
      propargylic alcohol and an alkene to obtain the corresponding bicyclo[3,1,0]hex-2
      ene derivative. These sequential reactions provide a conceptually new type of
      cycloaddition system between propargylic alcohols and alkenes.

PMID- 15584742
TI  - Calix[4]pyrrole[2]carbazole: a new kind of expanded calixpyrrole.
AB  - The synthesis and anion binding properties of a new class of calixpyrrole
      analogue, containing two carbazole subunits in lieu of two of the four acetone
      bridging elements normally found in calix[4]pyrrole, is described. The compound
      exists in a winglike structure in the solid state, as judged from single-crystal
      X-ray diffraction analyses of both the free system and the corresponding benzoate
      anion complex. Evidence for anion binding in dichloromethane solution was
      obtained from static fluorescent quenching experiments; these latter revealed a
      slight preference for acetate relative to other carboxylate anions (e.g.,
      benzoate, oxalate, succinate), as well as various other anionic substrates (i.e.,
      chloride and dihydrogen phosphate). No evidence of binding was observed in the
      case of bromide, nitrate, and hydrogen sulfate.

PMID- 15584743
TI  - A library of spirooxindoles based on a stereoselective three-component coupling
      reaction.
AB  - A collection of structurally complex and chemically diverse small molecules is a
      useful tool to explore cell circuitry. In this article, we report the split-pool
      synthesis of more than 3000 spirooxindoles on high capacity macrobeads. The key
      reaction to assemble the spirooxindole core stereoselectively is a Lewis acid
      variant of the Williams' three-component coupling. After formation, the skeleton
      was elaborated using Sonogashira couplings, amide forming reactions, and N
      acylations of gamma-lactams. The final library was analyzed by sampling
      individual macrobeads and by using binomial confidence limits. It was determined
      that at least 82% of the library compounds should have better than 80% purity. To
      demonstrate the utility of our discovery process, a high-throughput chemical
      genetic modifier screen was performed using stock solutions of the resultant
      products. A number of positives were identified as enhancers of the cellular
      actions of latrunculin B, an actin polymerization inhibitor. Through resynthesis,
      we confirmed one of the positives and demonstrated that, in yeast cells, it has
      an EC50 in the sub-micromolar range.

PMID- 15584744
TI  - Allylic ionization versus oxidative addition into vinyl C-X bonds by Pd with
      polyfunctional olefin templates.
AB  - The chemoselectivity of activation by a (PPh3)4Pd catalyst on a series of small,
      olefin-based compounds that were substituted with a variety of allylic and
      vinylic functional groups was studied. Of particular note, the allylic acetate of
      1-acetoxy-2-bromo-2-propene (7) was selectively ionized by Pd in the presence of
      a malonate nucleophile, while oxidative addition of the C-Br bond to Pd occurred
      exclusively in the presence of a boronic acid nucleophile. When the acetate
      nucleophile was used, no ionization of the acetate leaving group occurred at all,
      which was proven by the use of deuterium-labeled substrates (e.g., 11). This
      report demonstrates that the nucleophile interacts in some way with Pd prior to
      catalyst activation of the substrate. Certainly in the case of the malonate
      nucleophile, this is without precedent and contradicts the central dogma of how
      these proposed catalytic cycles operate.

PMID- 15584745
TI  - Hemiortho esters and hydrotrioxides as the primary products in the low
      temperature ozonation of cyclic acetals: an experimental and theoretical
      investigation.
AB  - Low-temperature ozonation (-78 degrees C) of 1,3-dioxolanes 1a-1f and 1,3
      dioxanes 1g and h in acetone-d6, methyl acetate, and tert-butyl methyl ether
      produced both the corresponding hemiortho esters (2a-h, ROH) and acetal
      hydrotrioxides (3a-h, ROOOH) in molar ratios ROH/ROOOH ranging from 0.5 to 23.
      Both types of intermediates were fully characterized by 1H, 13C, and 17O NMR
      spectroscopy. DFT calculations suggest that ozone abstracts a hydride ion from 1
      to form an ion pair, R+ -OOOH, which subsequently collapses to either the
      corresponding hemiortho ester (ROH) or the acetal hydrotrioxide (ROOOH).
      Hemiortho esters decomposed quantitatively into the corresponding hydroxy esters.
      Experimentally obtained activation parameters for the decomposition of 2a (E(a) =
      13.5 +/- 1.0 kcal/mol, log A = 8.3 +/- 1.0) are in accord with a highly oriented
      transition state involving, according to B3LYP calculations (deltaH(a)(298) =
      13.2 kcal/mol), two molecules of water as a bifunctional catalyst. This mechanism
      is also supported by the magnitude of the solvent isotope effect for the
      decomposition of 2e, i.e., k(H2O)/k(D2O) = 4.6 +/- 1.2. Besides the hydroxy
      esters and oxygen (3O2/1O2), dihydrogen trioxide (HOOOH) was formed in the
      decomposition of most of the acetal hydrotrioxides (ROOOH) investigated. The
      activation parameters for the decomposition of the hydrotrioxides 3a-e in various
      solvents were E(a) = 20 +/- 2 kcal/mol, log A = 13.5 +/- 1.5. Several mechanistic
      possibilities for the decomposition of ROOOH were tested by experiment and
      theory. The formation of the hydroxy esters and oxygen could be explained by the
      intramolecular transfer of the proton to form the hydroxy ester. The assistance
      of water in the decomposition of ROOOH to form the hydroxy esters, either
      directly or via hemiortho esters, was also investigated. According to DFT
      calculations, the formation of a hydroxy ester via hemiortho ester is
      energetically more favorable (deltaH(a)(298) = 14.5 kcal/mol), again due to the
      catalytic effect of two water molecules. HOOOH generation requires the
      involvement of water in the decomposition of ROOOH where the direct formation out
      of ROOOH is energetically preferred. The energy for a reaction between two
      molecules of water and singlet oxygen (delta1O2) is too high to occur in
      solution.

PMID- 15584746
TI  - Organogermanium reactive intermediates. The direct detection and characterization
      of transient germylenes and digermenes in solution.
AB  - Diphenylgermylene (Ph2Ge) and its Ge=Ge doubly bonded dimer, tetraphenyldigermene
      (6a), have been characterized directly in solution for the first time by laser
      flash photolysis methods. The germylene is formed via (formal) cheletropic
      photocycloreversion of 3,4-dimethyl-1,1-diphenylgermacyclopent-3-ene (4a), which
      is shown to proceed in high chemical (>95%) and quantum yield (phi = 0.62) by
      steady-state trapping experiments with methanol, acetic acid, isoprene, and
      triethylsilane. Flash photolysis of 4a in dry deoxygenated hexane at 23 degrees C
      leads to the prompt formation of a transient assigned to Ph2Ge (lambda(max) = 500
      nm; epsilon(max) = 1650 M(-1) cm(-1)), which decays with second-order kinetics
      (tau approximately 3 micros), with the concomitant growth of a second transient
      species that is assigned to digermene 6a (tau approximately 40 micros;
      lambda(max) = 440 nm). Analogous results are obtained from 1,1-dimesityl- and 1,1
      dimethyl-3,4-dimethylgermacyclopent-3-ene (4b and 4c, respectively), which afford
      Mes2Ge (tau approximately 20 micros; lambda(max) = 560 nm) and Me2Ge (tau
      approximately 2 micros; lambda(max) = 480 nm), respectively, as well as the
      corresponding digermenes, tetramesityl- (6b; lambda(max) = 410 nm) and
      tetramethyldigermene (6c; lambda(max) = 370 nm). The results for the mesityl
      compound are compared to the analogous ones from laser flash photolysis of the
      known Mes2Ge/6b precursor, hexamesitylcyclotrigermane. The spectra of the three
      germylenes and two of the digermenes are in excellent agreement with calculated
      spectra, derived from time-dependent DFT calculations. Absolute rate constants
      for dimerization of Ph2Ge and Mes2Ge and for their reaction with n-butylamine and
      acetic acid in hexane at 23 degrees C are also reported.

PMID- 15584747
TI  - Cu[Au(CN)2]2(DMSO)2: golden polymorphs that exhibit vapochromic behavior.
AB  - Two polymorphs of an [Au(CN)2]-based coordination polymer, Cu[Au(CN)2]2(DMSO)2,
      one green (1) and one blue (2), have been identified. In polymorph 1, alternation
      of five-coordinate Cu(II) and [Au(CN)2]- units generates 1-D chains, while 2-D
      corrugated sheets are obtained in polymorph 2, which contains six-coordinate
      Cu(II) centers. Both polymorphs form 3-D networks by virtue of aurophilic
      interactions of 3.22007(5) A and 3.419(3) A, respectively, and show similar weak
      antiferromagnetic coupling, but have different thermal decomposition
      temperatures. They both show vapochromic properties and, importantly, despite
      their significantly different solid-state structures, the vapochromic behavior of
      the two polymorphs is essentially identical. Upon solvent exchange, both
      polymorphs convert to the same Cu[Au(CN)2]2(solvent)x complex (solvent = H2O,
      CH3CN, dioxane, N,N-dimethylformamide, pyridine, NH3). The Cu[Au(CN)2]2(DMF) and
      Cu[Au(CN)2]2(pyridine)2 complexes have very similar 2-D square grid structures,
      comparable to that of 2. The solvent molecules adsorbed by Cu[Au(CN)2]2 bind to
      the Cu(II) centers, thereby altering the visible spectrum associated with the
      Cu(II) chromophores and the number and frequency of the nu(CN) as well. The
      network-stabilizing gold-gold interactions and the flexible coordination sphere
      of Cu(II) probably facilitate reversible solvent exchange at room temperature.

PMID- 15584748
TI  - Studying and switching electron transfer: from the ensemble to the single
      molecule.
AB  - We report here on the systematic investigation of photoinduced intramolecular
      electron transfer (IET) in a series of donor-bridge-acceptor molecules as a means
      of understanding electron transport through the bridge. Perylenebisimide
      chromophores connected by various oligophenylene bridges are studied because
      their electron-transfer behavior can readily be monitored by following changes in
      the fluorescence intensity. We find dramatic switching of the IET behavior as the
      solvent polarity (dielectric constant) is increased. By combining steady-state
      and time-resolved fluorescence spectroscopy in a variety of solvents at multiple
      temperatures with standard theories of electron transfer, we determine parameters
      governing the IET behavior of these dimers, such as the electronic coupling
      through the bridges. We also deploy available ab initio quantum chemical methods
      to calculate the through-space component of the electronic coupling matrix
      element. Single-molecule investigations of the electron-transfer behavior also
      show that IET can be switched reversibly by a similar mechanism in an isolated
      individual molecule.

PMID- 15584749
TI  - Electronic structure and chemical bonding in MO(n)- and MO(n) clusters (M = Mo,
      W; n = 3-5): a photoelectron spectroscopy and ab initio study.
AB  - Photoelectron spectroscopy (PES) and ab initio calculations are combined to
      investigate the electronic structure of MO(n)- clusters (M = W, Mo; n = 3-5).
      Similar PES spectra were observed between the W and Mo species. A large energy
      gap between the first and second PES bands was observed for MO3- and correlated
      with a stable closed-shell MO3 neutral cluster. The electron binding energies of
      MO4- increase significantly relative to those of MO3-, and there is also an
      abrupt spectral pattern change between MO3- and MO4-. Both MO4- and MO5- give PES
      features with extremely high electron binding energies (>5.0 eV) due to oxygen-2p
      based orbitals. The experimental results are compared with extensive density
      functional and ab initio [CCSD(T)] calculations, which were performed to
      elucidate the electronic and structural evolution for the tungsten oxide
      clusters. WO3 is found to be a closed-shell, nonplanar molecule with C3v
      symmetry. WO4 is shown to have a triplet ground state (3A2) with D2d symmetry,
      whereas WO5 is found to be an unusual charge-transfer complex, (O2-)WO3+. WO4 and
      WO5 are shown to possess W-O* and O2-* radical characters, respectively.

PMID- 15584750
TI  - Enantioselective hydrogenation of imines in ionic liquid/carbon dioxide media.
AB  - The enantioselective hydrogenation of N-(1-phenylethylidene)aniline using
      cationic iridium complexes with chiral phosphinooxazoline ligands was studied as
      a chemical probe to assess the potential of ionic liquid/carbon dioxide (IL/CO2)
      media for, multiphase catalysis. The biphasic system leads to activation, tuning,
      and immobilization of the catalyst that would be impossible in classical organic
      solvent systems or in either of the two unconventional media separately. In
      particular it is demonstrated that (i) the presence of CO2 can be beneficial or
      even mandatory for efficient hydrogenation in the IL; (ii) the precursor is
      activated in the IL by anion exchange allowing one to use in situ catalysts;
      (iii) the anion of the IL greatly influences the selectivity of the catalyst;
      (iv) the products are readily isolated from the catalyst solution by CO2
      extraction without cross contamination of IL or catalyst; and (v) the IL leads to
      enhanced stability of the catalyst. These results are corroborated and
      rationalized on the basis of the physicochemical properties of the biphasic
      medium and the chemical characteristics of the catalytic systems.

PMID- 15584751
TI  - Differential transition-state stabilization in enzyme catalysis: quantum chemical
      analysis of interactions in the chorismate mutase reaction and prediction of the
      optimal catalytic field.
AB  - Chorismate mutase is a key model system in the development of theories of enzyme
      catalysis. To analyze the physical nature of catalytic interactions within the
      enzyme active site and to estimate the stabilization of the transition state (TS)
      relative to the substrate (differential transition state stabilization, DTSS), we
      have carried out nonempirical variation-perturbation analysis of the
      electrostatic, exchange, delocalization, and correlation interactions of the
      enzyme-bound substrate and transition-state structures derived from ab initio
      QM/MM modeling of Bacillus subtilis chorismate mutase. Significant TS
      stabilization by approximately -23 kcal/mol [MP2/6-31G(d)] relative to the bound
      substrate is in agreement with that of previous QM/MM modeling and contrasts with
      suggestions that catalysis by this enzyme arises purely from conformational
      selection effects. The most important contributions to DTSS come from the
      residues, Arg90, Arg7, Glu78, a crystallographic water molecule, Arg116, and
      Arg63, and are dominated by electrostatic effects. Analysis of the differential
      electrostatic potential of the TS and substrate allows calculation of the
      catalytic field, predicting the optimal location of charged groups to achieve
      maximal DTSS. Comparison with the active site of the enzyme from those of several
      species shows that the positions of charged active site residues correspond
      closely to the optimal catalytic field, showing that the enzyme has evolved
      specifically to stabilize the TS relative to the substrate.

PMID- 15584752
TI  - Theoretical analysis of the smallest carbon cluster containing a planar
      tetracoordinate carbon.
AB  - A series of molecules, based on the smallest carbon cluster with one planar
      tetracoordinate carbon atom, C5(2-), are presented. To gain a better
      understanding about which electronic factors contribute to their stabilization,
      several global reactivity indexes, molecular scalar fields, and magnetic
      responses were calculated. The optimized bond lengths and the topological
      analysis of the electron density show that the central carbon atom in the parent
      dianion C5(2-) has a planar local environment, and it is coordinated to four
      other carbon atoms. The bonding of the parent dianion with the metal cations is
      highly ionic. The magnetic properties show that the C5(2-) derivatives are
      strongly diatropic and have a remarkable transferability of structural and
      electronic features from the anion to the salts. The theoretical analysis
      suggests that the lithium salt, C5Li2, is the most plausible candidate for
      experimental detection.

PMID- 15584753
TI  - Extraction of Au nanoparticles having narrow size distributions from within
      dendrimer templates.
AB  - Here, we show that Au nanoparticles having diameters of less than 2.2 nm can be
      extracted from within the interior of PAMAM dendrimers using n-alkanethiol
      extractants. Extraction proceeds quickly, regardless of the size of the
      nanoparticle, the dendrimer generation, or the peripheral functionalization of
      the dendrimer. The extraction rate is fastest for the lowest generation
      dendrimers, the smallest nanoparticles, and the shortest chain-length n
      alkanethiols. Other important results of this study include the following. First,
      within the accuracy of absorbance spectroscopy, the extraction yield is
      quantitative. Second, NMR and FT-IR spectroscopy indicate that after extraction
      the dendrimer remains in the aqueous phase and can be used to template additional
      metal particles. Third, the size and optical characteristics of the extracted
      nanoparticles are the same as the precursor dendrimer-encapsulated nanoparticles
      (DENs). Fourth, a 100-fold excess of n-alkanethiol molecules is required to
      prevent aggregation of DENs during extraction.

PMID- 15584754
TI  - An enantioselective fluorescent sensor for sugar acids.
AB  - Chiral fluorescent boronic acid 1 was found to be a highly enantioselective,
      chemoselective, and sensitive sensor for sugar acids, such as tartaric acid.
      Enantioselectivities (K(R)/K(S)) of up to 550:1, chemoselectivity up to 11,000:1,
      and sensitivities in the micromolar range with sensor 1 were observed. Single
      crystal X-ray analysis was used to confirm the structure of the fluorescent
      species.

PMID- 15584755
TI  - Porphyrin boxes constructed by homochiral self-sorting assembly: optical
      separation, exciton coupling, and efficient excitation energy migration.
AB  - meso-Pyridine-appended zinc(II) porphyrins Mn and their meso-meso-linked dimers
      Dn assemble spontaneously, in noncoordinating solvents such as CHCl3, into
      tetrameric porphyrin squares Sn and porphyrin boxes Bn, respectively.
      Interestingly, formation of Bn from Dn proceeds via homochiral self-sorting
      assembly, which has been verified by optical separations of B1 and B2. Optically
      pure enantiomers of B1 and B2 display strong Cotton effects in the CD spectra,
      which reflect the length of the pyridyl arm, thus providing evidence for the
      exciton coupling between the noncovalent neighboring porphyrin rings. Excitation
      energy migration processes within Bn have been investigated by steady-state and
      time-resolved spectroscopic methods in conjunction with polarization anisotropy
      measurements. Both the pump-power dependence on the femtosecond transient
      absorption and the transient absorption anisotropy decay profiles are directly
      associated with the excitation energy migration process within the Bn boxes,
      where the exciton-exciton annihilation time and the polarization anisotropy rise
      time are well described in terms of the Forster-type incoherent energy hopping
      model by assuming a number of hopping sites of N = 4 and an exciton coherence
      length of L = 2. Consequently, the excitation energy hopping rates between the
      zinc(II) diporphyrin units have been estimated for B1 (48 ps)(-1), B2 (98 +/- 3
      ps)(-1), and B3 (361 +/- 6 ps)(-1). Overall, the self-assembled porphyrin boxes
      Bn serve as a well-defined three-dimensional model for the light-harvesting
      complex.

PMID- 15584756
TI  - Oriented attachment and membrane reconstitution of His-tagged cytochrome c
      oxidase to a gold electrode: in situ monitoring by surface-enhanced infrared
      absorption spectroscopy.
AB  - A novel concept is introduced for the oriented incorporation of membrane proteins
      into solid supported lipid bilayers. Recombinant cytochrome c oxidase solubilized
      in detergent was immobilized on a chemically modified gold surface via the
      affinity of its histidine-tag to a nickel-chelating nitrilo-triacetic acid (NTA)
      surface. The oriented protein monolayer was reconstituted into the lipid
      environment by detergent substitution. The individual steps of the surface
      modification, including (1) chemical modification of the gold support, (2)
      adsorption of the protein, and (3) reconstitution of the lipid bilayer, were
      followed in situ by means of surface-enhanced infrared absorption spectroscopy
      (SEIRAS) and accompanied by normal-mode analysis. The high surface sensitivity of
      SEIRAS allows for the identification of each chemical reaction process within the
      monolayer at the molecular level. Finally, full functionality of the surface
      tethered cytochrome c oxidase was demonstrated by cyclic voltammetry after
      binding of the natural electron donor cytochrome c.

PMID- 15584757
TI  - Catalytic roles of active-site amino acid residues of coenzyme B12-dependent diol
      dehydratase: protonation state of histidine and pull effect of glutamate.
AB  - The hydrogen abstraction and the OH migration processes catalyzed by diol
      dehydratase are discussed by means of a quantum mechanical/molecular mechanical
      method. To evaluate the push effect of His143 and the pull effect of Glu170, we
      considered three kinds of whole-enzyme model, the protonated and two unprotonated
      His143 models. A calculated activation energy for the hydrogen abstraction by the
      adenosyl radical is 15.6 (13.6) kcal/mol in the protonated (unprotonated) His143
      model. QM/MM calculational results show that the mechanism of the OH migration is
      significantly changed by the protonation of His143. In the protonated His143
      model, the OH group migration triggered by the full proton donation from the
      imidazolium to the migrating OH group occurs by a stepwise OH abstraction/re
      addition process in which the water production reduces the barrier for the C-O
      bond cleavage. On the other hand, the OH migration in the unprotonated His143
      model proceeds in a concerted manner, as we previously proposed using a simple
      model including only K+ ion and substrate. The latter mechanism seems to be
      kinetically more favorable from the calculated energy profiles and is consistent
      with experimental results. The activation barrier of the OH group migration step
      is only 1.6 kcal/mol reduced by the hydrogen-bonding interaction between the O2
      of the substrate and unprotonated His143. Thus, it is predicted that His143 is
      not protonated, and therefore the main active-site amino acid residue that lowers
      the energy of the transition state for the OH group migration is determined to be
      Glu170.

PMID- 15584758
TI  - Influence of halogenation on the properties of uracil and its noncovalent
      interactions with alkali metal ions. Threshold collision-induced dissociation and
      theoretical studies.
AB  - The influence of halogenation on the properties of uracil and its noncovalent
      interactions with alkali metal ions is investigated both experimentally and
      theoretically. Bond dissociation energies of alkali metal ion-halouracil
      complexes, M+(XU), are determined using threshold collision-induced dissociation
      techniques in a guided ion beam mass spectrometer, where M+ = Li+, Na+, and K+
      and XU = 5-fluorouracil, 5-chlorouracil, 6-chlorouracil, 5-bromouracil, and 5
      iodouracil. The structures and theoretical bond dissociation energies of these
      complexes are determined from ab initio calculations. Theoretical calculations
      are also performed to examine the influence of halogenation on the acidities,
      proton affinities, and Watson-Crick base pairing energies. Halogenation of uracil
      is found to produce a decrease in the proton affinity, an increase in the alkali
      metal ion binding affinities, an increase in the acidity, and stabilization of
      the A::U base pair. In addition, alkali metal ion binding is expected to lead to
      an increase in the stability of nucleic acids by reducing the charge on the
      nucleic acid in a zwitterion effect as well as through additional noncovalent
      interactions between the alkali metal ion and the nucleobases.

PMID- 15584759
TI  - Planar tetra-, penta-, hexa-, hepta-, and octacoordinate silicons: a universal
      structural pattern.
AB  - A universal structural pattern has been presented at density function theory
      level to incorporate planar tetra-, penta-, hexa-, hepta-, and octacoordinate
      silicons in C2v B(n)E2Si series (E = CH, BH, or Si; n = 2-5) and D8h B8Si. The
      equivalence in valence electron counts and one-to-one correspondence of the
      delocalized pi and sigma valence orbitals with small boron clusters strongly
      support the optimized structures containing planar coordinate silicons. Planar
      B(n)E2Si series are predicted to be aromatic in nature, and the vertical
      detachment energies of their anions are presented to facilitate future
      photoelectron experiments. This structural pattern can be applied to form other
      planar coordinate nonmetals including Ge, P, As, Al, and Ga and needs to be
      confirmed in experiments to open a new branch of chemistry on planar coordinate
      main group elements.

PMID- 15584760
TI  - A DFT study of the ground state multiplicities of linear vs angular
      polyheteroacenes.
AB  - Unrestricted density functional calculations in combination with the broken
      symmetry approach and spin-projection methods have been employed to study a
      series of formally 4n pi antiaromatic linear and angular polyheteroacenes.
      Calculations show that the linear polyheteroacene molecules have either stable
      singlet zwitterionic 6-9 or singlet diradical 5 ground states because they
      sacrifice the aromaticity of the central arene to form two independent cyanines.
      The corresponding angular compounds 10-14 have robust triplet states, since they
      cannot create independent cyanines to escape their overall antiaromaticity. An
      analysis based on the SOMO-SOMO energy splittings, their spatial distributions,
      and the spin density populations for the triplet states is presented to clarify
      the factors that determine their ground state multiplicities.

PMID- 15584761
TI  - Autocatalytic formation of green heme: evidence for H2O2-dependent formation of a
      covalent methionine-heme linkage in ascorbate peroxidase.
AB  - The mammalian heme peroxidases are distinguished from their plant and fungal
      counterparts by the fact that the heme group is covalently bound to the protein
      through ester links from glutamate and aspartate residues to the heme 1- and 5
      methyl groups and, in the case of myeloperoxidase, through an additional
      sulfonium link from the Cbeta of the 2-vinyl group to a methionine residue. To
      duplicate the sulfonium link in myeloperoxidase and to obtain information on its
      mechanism of formation, we have engineered a methionine residue close to the 2
      vinyl group in recombinant pea cytosolic ascorbate peroxidase (rpAPX) by
      replacement of Ser160 by Met (S160M variant). The S160M variant is isolated from
      Escherichia coli as apo-protein. Reconstitution of apo-S160M with exogenous heme
      gives a red protein (S160M(R)) which has UV-visible (lambda(max)/nm = 407, 511,
      633) and steady-state kinetic (kcat = 156 +/- 7 s(-1), KM = 102 +/- 15 microM)
      properties that are analogous to those of rpAPX. The reaction of S160M(R) with
      H2O2 gives a green protein (S160M(G)). Electronic spectroscopy, mass
      spectrometry, and HPLC analyses are consistent with the formation of a covalent
      linkage between the methionine residue and the heme vinyl group in S160M(G).
      Single-wavelength and photodiode array stopped-flow kinetic analyses identify a
      transient Compound I species as a reaction intermediate. The results provide the
      first direct evidence that covalent heme linkage formation occurs as an H2O2
      dependent process that involves Compound I formation. A mechanism that is
      consistent with the data is presented.

PMID- 15584762
TI  - Diastereoselective self-assembly of chiral diamine-chelated aryllithiums to
      dimeric aggregates.
AB  - Aryllithium compounds [LiC6H4(CH2N(Et)CH2CH2NEt2)-2]2 (2b),
      [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(R))-2]2 ((R)-3b), and
      [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(rac))-2]2 ((rac)-3b) were synthesized and
      characterized in the solid state and in solution. X-ray crystallographic studies
      of 2b and (R)-3b and molecular weight determinations of 2b, (R)-3b, and (rac)-3b
      by cryoscopy in benzene showed that, both in the solid state and in apolar,
      noncoordinating solvents such as benzene, these compounds exist as discrete
      dimeric aggregates. For (R)-3b and (rac)-3b the aggregation process of two
      monomeric aryllithium units to one dimer is highly diastereoselective.

PMID- 15584763
TI  - Charged gels as orienting media for measurement of residual dipolar couplings in
      soluble and integral membrane proteins.
AB  - Measurement of residual dipolar couplings for membrane proteins will dramatically
      improve the quality of the structures obtainable by solution NMR spectroscopy.
      While there has been some success in achieving alignment of membrane-bound
      peptides, there has been very limited success in achieving alignment for
      functional membrane proteins. Herein, we demonstrate that charged polyacrylamide
      based copolymers are suitable for obtaining weak alignment of membrane proteins
      reconstituted in detergent micelles. Varying the copolymer compositions, we
      prepared positively, zwitterionic, and negatively charged gels that are very
      stable at low concentration and can be used for obtaining weak alignment by
      compression in an NMR tube. Application of this method is demonstrated for the
      integral membrane protein OmpA in DPC micelles.

PMID- 15584764
TI  - Channel activity of a viral transmembrane peptide in micro-BLMs: Vpu(1-32) from
      HIV-1.
AB  - We report for the first time on pore-suspending lipid bilayers, which we call
      micro-black lipid membranes (micro-BLMs), based on a highly ordered macroporous
      silicon array. Micro-BLMs were established by first functionalizing the backside
      porous silicon surface with gold and then chemisorbing 1,2-dipalmitoyl-sn-glycero
      3-phosphothioethanol followed by spreading 1,2-diphytanoyl-sn-glycero-3
      phosphocholine dissolved in n-decane. Impedance spectroscopy revealed the
      formation of single lipid bilayers confirmed by a mean specific capacitance of
      0.6 +/- 0.2 microF/cm2. Membrane resistances were in the G omega-regime and
      beyond. The potential of the system for single channel recordings was
      demonstrated by inserting the transmembrane domain of the HIV-1 accessory peptide
      Vpu(1-32), which forms helix bundles with characteristic opening states. We
      elucidated different amilorides as potential drugs to inhibit channel activity of
      Vpu.

PMID- 15584765
TI  - Compositional and Moisture Content Effects on the Biodegradability of
      Zein/Ethylcellulose Films.

PMID- 15584766
TI  - The role of stimulants in the treatment of preschool children with attention
      deficit hyperactivity disorder.
AB  - The symptoms of attention-deficit hyperactivity disorder (ADHD) can have an early
      onset, beginning before the age of 6 years. Despite the significant number of
      preschool-aged children that can be diagnosed with ADHD, there are limited
      controlled data available on the pharmacological interventions being increasingly
      used in this population. A 1990 review showed that 34% of paediatricians and 15%
      of family physicians had prescribed psychostimulant medications to preschoolers
      with ADHD, and pharmacoepidemiological studies indicate growing use of stimulants
      in preschoolers during the 1990s. Unfortunately, only six controlled trials, with
      a total enrollment of less than 200 children, have been conducted using these
      drugs in preschoolers. While these small studies provide some evidence of benefit
      from the use of methylphenidate in preschoolers with ADHD, more data are
      critically needed. Practice parameters developed by the American Academy of Child
      & Adolescent Psychiatry and the American Academy of Pediatrics provide some
      guidance regarding the diagnosis and treatment of young children with ADHD, but
      are mainly based upon research in children of primary-school age. The ongoing
      PATS (Preschool ADHD Treatment Study), funded by the National Institute of Mental
      Health, will provide important clinical guidance for diagnostic considerations
      and intervention strategies for children with ADHD aged 3-5 years. Pending the
      release of data from the PATS study, clinicians must rely on developmental
      assessment skills, available standardised rating instruments, reports about the
      child from multiple informants, and knowledge of the risks and benefits of
      available pharmacological and behavioural treatments, in order to treat preschool
      children with ADHD effectively.

PMID- 15584767
TI  - The role of creatine in the management of amyotrophic lateral sclerosis and other
      neurodegenerative disorders.
AB  - Creatine is consumed in the diet and endogenously synthesised in the body. Over
      the past decade, the ergogenic benefits of synthetic creatine monohydrate have
      made it a popular dietary supplement, particularly among athletes. The anabolic
      properties of creatine also offer hope for the treatment of diseases
      characterised by weakness and muscle atrophy. Moreover, because of its cellular
      mechanisms of action, creatine offers potential benefits for diseases involving
      mitochondrial dysfunction. Recent data also support the hypothesis that creatine
      may have a neuroprotective effect. Amyotrophic lateral sclerosis (ALS) is
      characterised by progressive degeneration of motor neurons, resulting in
      weakening and atrophy of skeletal muscles. In patients with this condition,
      creatine offers potential benefits in terms of facilitating residual muscle
      contractility as well as improving neuronal function. It may also help stabilise
      mitochondrial dysfunction, which plays a key role in the pathogenesis of ALS.
      Indeed, the likely multifactorial aetiology of ALS means the combined
      pharmacodynamic properties of creatine offer promise for the treatment of this
      condition. Evidence from available animal models of ALS supports the utility of
      treatment with creatine in this setting. Limited data available in other
      neuromuscular and neurodegenerative diseases further support the potential
      benefit of creatine monohydrate in ALS. However, few randomised, controlled
      trials have been conducted. To date, two clinical trials of creatine monohydrate
      in ALS have been completed without demonstration of significant improvements in
      overall survival or a composite measure of muscle strength. These trials have
      also posed unanswered questions about the optimal dosage of creatine and its
      beneficial effects on muscle fatigue, a measure distinct from muscle strength. A
      large, multicentre, clinical trial is currently underway to further investigate
      the efficacy of creatine monohydrate in ALS and address these unresolved issues.
      Evidence to date shows that creatine supplementation has a good safety profile
      and is well tolerated by ALS patients. The purpose of this article is to provide
      a short, balanced review of the literature concerning creatine monohydrate in the
      treatment of ALS and related neurodegenerative diseases. The pharmacokinetics and
      rationale for the use of creatine are described along with available evidence
      from animal models and clinical trials for ALS and related neurodegenerative or
      neuromuscular diseases.

PMID- 15584768
TI  - Therapeutic potential of platelet glycoprotein IIb/IIIa receptor antagonists in
      acute ischaemic stroke: scientific rationale and available evidence.
AB  - Acute ischaemic stroke is the result of an abrupt interruption of focal cerebral
      blood flow. In the majority of cases, this interruption is caused by an acute
      thromboembolism. Based on clinical experience in the treatment of acute coronary
      syndromes, platelet glycoprotein (GP) IIb/IIIa receptor antagonists alone, in
      combination with reduced doses of thrombolytic agents, or as complementary
      therapy for short-term mechanical interventions merit consideration as a class of
      agents with potential use in ischaemic stroke. Research to date and extrapolation
      from the cardiac literature suggest significant, but as yet unproven, potential
      for the use of GP IIb/IIIa receptor antagonists in the treatment of acute
      ischaemic stroke. This potential exists both at the site of the thromboembolic
      occlusion and at the distal microvascular level. This article reviews the
      scientific rationale and available evidence for the potential use of platelet GP
      IIb/IIIa receptor antagonists in acute ischaemic stroke.

PMID- 15584769
TI  - Obsessive-compulsive disorder in schizophrenia: clinical characteristics and
      treatment.
AB  - There is a considerable overlap of schizophrenia and obsessive-compulsive
      disorder (OCD) in the structural and functional brain abnormalities involved,
      role of the dopamine/serotonin neurotransmitter systems, and some demographic and
      clinical characteristics. Although OCD co-occurs in a substantial proportion of
      schizophrenia patients, a systematic evaluation of the clinical features and
      treatment of this population is lacking. This review critically evaluates
      findings of recent studies pertaining to the rate of occurrence of OCD or
      obsessive-compulsive symptoms (OCS) in schizophrenia and the clinical
      characterisation of the schizo-obsessive subtype. Specifically,
      interrelationships between obsessive-compulsive and schizophrenic symptoms in
      terms of temporal relationships and their association with specific schizophrenia
      subtypes and the effect of OCS on the severity of schizophrenia symptoms are
      addressed. In the absence of evidence-based data, tentative therapeutic
      approaches in this difficult-to-treat patient subgroup are suggested. These
      include monotherapy with atypical antipsychotic agents or a combination of either
      typical or atypical antipsychotics with SSRIs or clomipramine. The clinical
      characteristics of antipsychotic-induced OCS/OCD are also presented to facilitate
      identification and management of this rare but clinically significant adverse
      effect. Finally, future directions of research in schizophrenia-OCD comorbidity
      relevant to clinical practice are discussed.

PMID- 15584770
TI  - New formulations of stimulants for attention-deficit hyperactivity disorder:
      therapeutic potential.
AB  - New formulations of stimulant medications for the treatment of attention-deficit
      hyperactivity disorder (ADHD) have been an important focus for pharmaceutical
      industry research and development over the past decade. In this article, we
      review and assess the therapeutic potential of five new stimulant formulations
      (one immediate release and four longer-acting preparations) that have recently
      become available for the treatment of ADHD. While the therapeutic potential of
      immediate-release enantiomers of methylphenidate has not yet been clinically
      realised, new long-acting formulations of stimulants have changed the standard of
      care for children, adolescents and adults with ADHD. The longer duration of
      action of these once-daily compounds, and the consequent expansion of the
      duration of daily ADHD coverage afforded by them, has introduced the realistic
      possibility of reducing the overall daily burden of ADHD on affected individuals.
      Although more expensive, these new stimulant formulations are easier for patients
      to use than older stimulants, more resistant to abuse and misuse, and allow for
      increased privacy of ADHD treatment at school or work.

PMID- 15584772
TI  - Changes in the room-temperature emission spectrum of chlorophyll during fast and
      slow phases of the Kautsky effect in intact leaves.
AB  - Changes in the room-temperature emission spectrum of chlorophyll (Chl) were
      analyzed using fast diode-array recordings during the Kautsky effect in mature
      and in greening barley leaves. In mature leaves, the comparison of F(O) (basal
      level of fluorescence yield at transient O) and F(M) (maximum level of
      fluorescence yield at transient M) spectra showed that the relative amplitude of
      total variable fluorescence was maximal for the 684 nm Photosystem II (PSII) band
      and minimal for the 725 nm Photosystem I band. During the increase from F(O) to
      F(M), a progressive redshift of the spectrum of variable fluorescence occurred.
      This shift reflected the different fluorescence rise kinetics of different layers
      of chloroplasts inside the leaf. This was verified by simulating the effect of
      screening on the emission spectrum of isolated chloroplasts and by experiments on
      greening leaves with low Chl content. In addition, experiments performed at
      different greening stages showed that the presence of uncoupled Chl at early
      greening stages and light-harvesting complex II (LHCII) at later stages have
      detectable but minor effects on the shape of room-temperature emission spectra.
      When strong actinic light was applied to mature green leaves, the slow
      fluorescence yield, which declined from F(M) to F(T) (steady-state level of
      fluorescence yield at transient T), was accompanied by a slight redshift of the
      684 nm PSII band because of nonphotochemical quenching of short-wavelength
      emitting Chl ascribed to LHCII.

PMID- 15584773
TI  - On the way to assess emotions in animals: do lambs (Ovis aries) evaluate an event
      through its suddenness, novelty, or unpredictability?
AB  - Appraisal theories provide a framework that gives insight into emotions and could
      allow comparisons across species. According to these theories, events are first
      evaluated on their suddenness, novelty, and unpredictability. The authors
      examined the ability of lambs (Ovis aries) to evaluate an event according to
      these 3 criteria through 3 tests. The lambs responded to suddenness with a
      startle response coupled with an increase in heart rate and to novelty with an
      orientation response coupled with an increase of vagal activity. There was no
      clear evidence that lambs can detect the predictability of an event. Those
      results support the usefulness of appraisal theories to assess emotion in
      animals.

PMID- 15584771
TI  - Pharmacotherapy of pervasive developmental disorders in children and adolescents.
AB  - Pervasive developmental disorders (PDDs) are severe psychiatric disorders
      characterised by impaired social interaction, reduced verbal and nonverbal
      communication, and restricted and stereotyped patterns of interest and behaviour,
      with onset in the first 3 years of life. As part of a multimodal approach that
      includes educational and behavioural interventions, appropriate use of
      pharmacotherapy in patients with PDDs can improve some symptoms and behaviours
      and increase the patient's response to nonpharmacological interventions.
      Pharmacotherapy is aimed at stabilising the dysregulated systems that are thought
      to underlie the abnormal behaviours, namely the serotonergic and dopaminergic
      systems.This paper critically reviews the available literature on the
      pharmacotherapy of PDDs in children and adolescents. Pharmacological, efficacy
      and safety data on drugs acting on serotonin (serotonergic agents such as
      clomipramine, fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine), on
      both serotonin and norepinephrine (venlafaxine and mirtazapine), dopamine
      (dopamine-blocking antipsychotics such as haloperidol and pimozide), and on both
      serotonin and dopamine (atypical antipsychotics such as clozapine, risperidone,
      olanzapine, quetiapine and ziprasidone) are presented. The paper concludes with a
      brief discussion of other psychotropic medications, such as the opioid
      antagonists, alpha-adrenoceptor agonists (clonidine and guanfacine),
      psychostimulants, mood stabilisers, glutamatergic compounds (lamotrigine,
      amantadine), buspirone, and secretin. Available evidence suggests that atypical
      antipsychotics (mainly risperidone and olanzapine) are particularly indicated
      when more serious behavioural symptoms, such as aggression, self-injurious
      behaviours and hyperactivity, are prominent. Serotonergic agents may be effective
      in children with repetitive phenomena or affective symptoms. Social relatedness
      is more frequently refractory to both atypical antipsychotics and serotonergic
      agents. Further research into the drug treatment of PDDs, including placebo
      controlled trials and long-term, naturalistic follow-up studies of large samples
      of patients of different age ranges, is warranted.

PMID- 15584774
TI  - Verbal attention getting as a key factor in social learning between dog (Canis
      familiaris) and human.
AB  - Pet dogs (Canis familiaris) learn to detour a V-shaped fence effectively from an
      unfamiliar human demonstrator. In this article, 4 main features of the
      demonstrator's behavior are highlighted: (a) the manipulation of the target, (b)
      the familiarity of the demonstrator, (c) the role of verbal attention-getting
      behavior, and (d) whether a strange trained dog could also be an effective
      demonstrator. The results show that the main factor of a successful human
      demonstration is the continuous verbal communication with the dog during
      detouring. It was also found that an unfamiliar dog demonstrator was as efficient
      as the unfamiliar experimenter. The experiments provide evidence that in adult
      dogs, communicative context with humans is needed for effective interspecific
      social learning to take place.

PMID- 15584775
TI  - Reorientation in a two-dimensional environment: II. Do pigeons (Columba livia)
      encode the featural and geometric properties of a two-dimensional schematic of a
      room?
AB  - Pigeons (Columba livia) searched for a hidden target area in images showing a
      schematic rectangular environment. The absolute position of the goal varied
      across trials but was constant relative to distinctive featural cues and
      geometric properties of the environment. Pigeons learned to use both of these
      properties to locate the goal. Transformation tests showed that pigeons could use
      either the color or shape of the features, but performance was better with color
      cues present. Pigeons could also use a single featural cue at an incorrect corner
      to distinguish between the correct corner and the geometrically equivalent
      corner; this indicates that they did not simply use the feature at the correct
      corner as a beacon. Interestingly, pigeons that were trained with features
      spontaneously encoded geometry. The encoded geometric information withstood
      vertical translations but not orientation transformations.

PMID- 15584776
TI  - Responses of white-faced capuchins (Cebus capucinus) to naturalistic and
      experimentally presented food-associated calls.
AB  - In the context of foraging, many animal species produce specific calls that
      attract others. Researchers hypothesize that these vocalizations function to
      inform others about food; however, few studies have investigated whether food
      associated calls alone are sufficient to cause individuals to respond as if they
      have been informed about food. Playback experiments on white-faced capuchins
      (Cebus capucinus) investigated whether listeners could infer the presence of food
      merely by hearing food-associated calls. Recipients looked significantly longer
      toward the call source and approached the speaker more often after hearing food
      associated calls, as compared with control calls. Because these responses are not
      indicative of feeding, it is unclear whether listeners associated the calls with
      food. Nonetheless, these responses, specific to food-associated calls, may
      increase individuals' chances of finding food.

PMID- 15584777
TI  - Categorization of above and below spatial relations by tufted capuchin monkeys
      (Cebus apella).
AB  - Using a matching-to-sample procedure, the researchers investigated tufted
      capuchins' (Cebus apella) ability to form categorical representations of above
      and below spatial relations. In Experiment 1, 5 capuchins correctly matched bar
      dot stimuli on the basis of the relative above and below location of their
      constituent elements. The monkeys showed a positive transfer of performance both
      when the bar-dot distance in the two comparison stimuli differed from that of the
      sample and when the actual location of the matching stimulus and the nonmatching
      stimulus on the apparatus was modified. In Experiment 2, the researchers
      systematically changed the shapes of the located object (the dot) or the
      reference object (the horizontal bar). These manipulations did not affect the
      monkeys' performance. Overall, the data suggest that capuchins can form abstract,
      conceptual-like representations for above and below spatial relations.

PMID- 15584778
TI  - Following and joining the informed individual in semifree-ranging tonkean
      macaques (Macaca tonkeana).
AB  - The authors investigated whether Tonkean macaques (Macaca tonkeana) can
      distinguish between 2 group mates with different knowledge and improve their
      foraging performance. The subjects were 8 young individuals belonging to a group
      raised in a 2-acre park. The authors carried out 192 tests in which subgroups of
      3 individuals were released in a food search situation. Two leaders could be
      informed about 2 different food sites. A naive follower could choose to follow 1
      leader or another. The follower could find the correct site when 1 leader was
      informed about food location. There was no evidence that the follower identified
      the best leader, however. The less well-informed leader generally joined the
      other leader, prompting the follower to follow them. The followers' pathways were
      mainly determined by the interactions of leaders.

PMID- 15584779
TI  - Do dogs (Canis familiaris) understand invisible displacement?
AB  - Domestic dogs (Canis familiaris) perform above chance on invisible displacement
      tasks despite showing few other signs of possessing the necessary
      representational abilities. Four experiments investigated how dogs find an object
      that has been hidden in 1 of 3 opaque boxes. Dogs passed the task under a variety
      of control conditions, but only if the device used to displace the object ended
      up adjacent to the target box after the displacement. These results suggest that
      the search behavior of dogs was guided by simple associative rules rather than
      mental representation of the object's past trajectory. In contrast, Experiment 5
      found that on the same task, 18- and 24-month-old children showed no disparity
      between trials in which the displacement device was adjacent or nonadjacent to
      the target box.

PMID- 15584780
TI  - Interplay between environmental and genetic factors in temperament/personality
      traits in horses (Equus caballus).
AB  - The aim of the present study was to broach the question of the relative influence
      of different genetic and environmental factors on different
      temperament/personality traits of horses (Equus caballus). The researchers
      submitted 702 horses to standardized experimental tests and investigated 9
      factors, either genetic or environmental. Genetic factors, such as sire or breed,
      seemed to influence more neophobic reactions, whereas environmental factors, such
      as the type of work, seemed to play a more dominant role in reactions to social
      separation or learning abilities. Additive effects were evident, showing how
      environmental factors may modulate behavioral traits. This study constitutes a
      first step toward understanding the relative weights of genetic factors and how
      the environment may intervene in determining individual behavioral
      characteristics.

PMID- 15584781
TI  - Call usage learning in gray seals (Halichoerus grypus).
AB  - Call usage learning can be demonstrated on 4 different levels: signaling on
      command, signaling and refraining from signaling on command, responding to a
      trained stimulus with a signal from a specific signal class, and responding to
      the playback of any untrained stimulus with one from the same signal class. Two
      young gray seals (Halichoerus grypus) were trained successfully to demonstrate
      the first 2 levels. They also learned to respond to 9 moan stimuli and 9 growl
      stimuli with vocalizations of the same class (Level 3). However, novel moan and
      growl stimuli tended to elicit growls. This casts doubt on the possibility that
      gray seals can reach the 4th level, but it demonstrates that they are capable of
      the first 3 levels of usage learning.

PMID- 15584782
TI  - Interpersonal control strivings and vulnerability to negative social exchanges in
      later life.
AB  - Although negative social exchanges detract from well-being, little is known about
      the factors that influence older adults' vulnerability to such exchanges.
      Interpersonal control strivings were examined as predictors of 2 dimensions of
      vulnerability to negative social exchanges, exposure and reactivity, in a
      nationally representative sample of older adults (N=916). Interpersonal control
      strivings refer to people's efforts to maintain harmony in their relationships
      and, when unsuccessful, to preserve their emotional health. The results revealed
      that interpersonal control strivings directed toward maintaining harmony were
      associated with less exposure, whereas interpersonal control strivings directed
      toward preserving emotional health when harmony is threatened were associated
      with less reactivity. Thus, complementary control processes play an important
      role in older adults' vulnerability to negative social exchanges.

PMID- 15584783
TI  - Cognitive skill learning: age-related differences in strategy shifts and speed of
      component operations.
AB  - Younger and older adults solved novel arithmetic problems and reported the
      strategies used for obtaining solutions. Age deficits were demonstrated in the
      latencies for computing and retrieving solutions and in the shift from
      computation to retrieval. Rates of improvement within age groups were parallel
      for computations and retrievals, suggesting a single, age-attenuated mechanism
      that affects practice-related speedup. The age-related delay in strategy shift
      suggests either reluctance to use retrieval or an associative memory deficit.
      Experiment 1 showed that skill acquisition was unaffected by the presence and
      frequency of postresponse strategy probes for both age groups. Experiment 2
      showed that pretraining item-learning operations facilitated subsequent item
      learning and that pretraining either item-learning operations or the algorithm
      did not alter the age trends.

PMID- 15584784
TI  - Relational integration, inhibition, and analogical reasoning in older adults.
AB  - The difficulty of reasoning tasks depends on their relational complexity, which
      increases with the number of relations that must be considered simultaneously to
      make an inference, and on the number of irrelevant items that must be inhibited.
      The authors examined the ability of younger and older adults to integrate
      multiple relations and inhibit irrelevant stimuli. Young adults performed well at
      all but the highest level of relational complexity, whereas older adults
      performed poorly even at a medium level of relational complexity, especially when
      irrelevant information was presented. Simulations based on a neurocomputational
      model of analogical reasoning, Learning and Inference with Schemas and Analogies
      (LISA), suggest that the observed decline in reasoning performance may be
      explained by a decline in attention and inhibitory functions in older adults.

PMID- 15584785
TI  - Apolipoprotein E and cognitive performance: a meta-analysis.
AB  - The epsilon4 allele of the apolipoprotein E (APOE) gene is a known risk factor
      for Alzheimer's disease and may also affect cognitive performance in normal
      aging. Evidence of the presence and magnitude of epsilon4-related cognitive
      deficits was examined with a meta-analysis of the available literature. Thirty
      eight studies were included, and cognitive performance was collapsed into 8
      domains. Results indicated significant APOE-epsilon4 group differences for global
      cognitive functioning, episodic memory, and executive functioning, in favor of
      non-epsilon4 carriers. In addition, older age and APOE-epsilon4 heterozygosity
      was associated with smaller epsilon4-related impairments. The meta-analysis
      results suggest that APOE-epsilon4 genotype does affect cognitive performance in
      healthy aging, although the influence is relatively small and specific to certain
      domains of cognitive performance.

PMID- 15584786
TI  - The relationship between age, verbal working memory, and language comprehension.
AB  - A structural modeling approach was used to examine the relationships between age,
      verbal working memory (vWM), and 3 types of language measures: online syntactic
      processing, sentence comprehension, and text comprehension. The best-fit model
      for the online-processing measure revealed a direct effect of age on online
      sentence processing, but no effect mediated through vWM. The best-fit models for
      sentence and text comprehension included an effect of age mediated through vWM
      and no direct effect of age. These results indicate that the relationship among
      age, vWM, and comprehension differs depending on the measure of language
      processing and support the view that individual differences in vWM do not affect
      individuals' online syntactic processing.

PMID- 15584787
TI  - A longitudinal study of implicit and explicit memory in old persons.
AB  - Decline in explicit memory with advancing age is a common finding, but it is
      unclear whether implicit memory (repetition priming) declines or remains stable.
      Meta-analyses of studies that examined differences between extreme groups (young
      old), typically at a single point in time and on a single test, suggest that a
      mild reduction in priming occurs with advancing age. The authors examined
      explicit memory and priming, on multiple tests over 4 annual data-collection
      waves, in a large group of older persons without dementia at baseline. Explicit
      memory declined significantly, but priming remained stable. Findings indicate
      that explicit memory and priming are dissociable on the basis of age-related
      change and that mildly reduced priming is not an inevitable consequence of
      growing older.

PMID- 15584788
TI  - Adult age differences in self-regulated learning from reading sentences.
AB  - We examined age differences in the heuristic used to allocate effort in learning
      information from sentences. Younger and older adults read and reread sentences
      varying in propositional density for recall, making judgments of learning before
      producing recall. The allocation of effort in rereading items that were less well
      learned on the first reading was optimized for sentences of intermediate
      complexity, especially for older adults. These data support a model of self
      regulated learning in which readers reduce the discrepancy between current and
      optimal states of learning. However, self-regulation, which may be procedure
      based or rely on an implicit representation of the current state of learning, may
      be particularly efficient for older adults within a region of proximal learning.

PMID- 15584789
TI  - A descriptive epidemiology of lifetime trauma and the physical health status of
      older adults.
AB  - Three issues are evaluated in this study. The 1st involves examining the
      relationship between exposure to trauma over the life course and physical health
      status in old age. The 2nd has to do with seeing whether the relationship between
      trauma and health varies across 3 cohorts of older adults: the young-old (ages 65
      74), the old-old (ages 75-84), and the oldest old (age 85 and over). The 3rd
      issue involves seeing whether the age at which a trauma was encountered is
      related to health in late life. Data from a nationwide survey of older people
      (N=1,518) reveal that trauma is associated with worse health. Moreover, the young
      old appear to be at greatest risk. Finally, data suggest that trauma arising
      between the ages of 18 and 30 years, as well as ages 31 to 64 years, has the
      strongest relationship with current health.

PMID- 15584790
TI  - Can practice overcome age-related differences in the psychological refractory
      period effect?
AB  - Can dual-task practice remove age-related differences in the psychological
      refractory period (PRP) effect? To answer this question, younger and older
      individuals practiced 7 blocks of a PRP design, in which Task 1 (T1) required a
      vocal response to an auditory stimulus and Task 2 (T2) required a manual response
      to a visual stimulus (Experiment 1). The results showed that practice did not
      reduce, but rather increased, age-related differences in PRP interference. Using
      the trained individuals, the introduction of a less complex new T1 (Experiment 2)
      or a less complex new T2 (Experiment 3) with the task previously practiced
      reduced the PRP interference but only in older adults. The authors propose that
      older adults suffer from a large task-switch cost that is more sensitive to task
      complexity than to the amount of practice.

PMID- 15584791
TI  - Positive aspects of caregiving and adaptation to bereavement.
AB  - This study examined how positive aspects of caregiving affect adaptation to
      bereavement among older adults who cared for a family member with dementia. The
      sample consisted of 217 caregivers who were part of the Resources for Enhancing
      Alzheimer's Caregiver Health Study. Using pre- and postloss data, hierarchical
      regressions were carried out to examine the effects of positive aspects of
      caregiving (caregiving benefit) on postloss depression and grief. Findings show
      that preloss caregiving benefit was associated with higher levels of postloss
      depression and grief, even after controlling for caregiver demographic
      characteristics, contextual factors, and caregiving burden. This effect was
      particularly strong for the relation between benefit and grief. Results
      demonstrate the importance of studying both positive and negative aspects of
      caregiving and their relation to bereavement outcomes.

PMID- 15584792
TI  - Predictors of subjective age before and after cataract surgery: conscientiousness
      makes a difference.
AB  - This study contributes to research on subjective age by examining the interplay
      of felt age with health, functional limitations, and personality. Individuals
      undergoing cataract surgery (N=134; 38 to 92 years of age) provided data for an
      assessment period of 6 weeks surrounding their scheduled surgery.
      Conscientiousness and repeated measurements of health indicators, functional
      limitations, and felt age were included in the analyses. Results indicated that
      functional limitations may be more important to the construction of felt age than
      their underlying health-related causes. Moreover, conscientious participants felt
      younger before and after surgery. Their functional status was less dependent on
      health than the functional status of less conscientious participants. This
      moderator effect is discussed along with health-related pathways leading to felt
      age.

PMID- 15584793
TI  - Specific- and partial-source memory: effects of aging.
AB  - Normal aging can be associated with impairments in source memory (recollecting an
      event's context). This study examined the effects of aging on specific-source
      memory (e.g., remembering which of 4 people spoke a word) and partial-source
      memory (e.g., remembering the gender of the person who spoke the word). When
      young and older adults were matched in terms of old-new recognition, age-related
      deficits were observed on both specific- and partial-source recollection. When
      the groups were matched on partial-source performance, no disproportionate
      specific-source impairment was seen. The results suggest that aging does not
      differentially affect specific- versus partial-source memory.

PMID- 15584794
TI  - Spanish and English Neuropsychological Assessment Scales (SENAS): further
      development and psychometric characteristics.
AB  - The Spanish and English Neuropsychological Assessment Scales were devised to be a
      broad set of psychometrically matched measures with equivalent Spanish and
      English versions. Study 1 in this report used item response theory methods to
      refine scales. Results strongly supported psychometric matching across English
      and Spanish versions and, for most scales, within English and Spanish versions.
      Study 2 supported in both English and Spanish subsamples the 6-domain model of
      ability that guided scale construction. Study 3 examined differential item
      functioning (DIF) of one scale (Object Naming) in relation to education,
      ethnicity, gender, and age. Effects of DIF on scale-level ability scores were
      limited. Results demonstrate an empirically guided psychometric approach to test
      construction for multiethnic and multilingual test applications.

PMID- 15584795
TI  - Development and validation of a Rasch-derived CES-D short form.
AB  - The current study presents a Rasch-derived short form of the Center for
      Epidemiologic Studies-Depression scale (CES-D) for use as a depression screening
      tool in the general population. In contrast to short forms developed with
      reliance on classical measurement techniques, those developed using techniques
      based on item response theory produce a measure that offers true interval
      scaling, provide enhanced information about responders with extreme scores, and
      expand understanding of the underlying latent structure. Cross-validation of the
      Rasch-derived CES-D short form supported its utility and structural validity
      across samples. Tests of structural validity using latent variable modeling
      methodology indicated that a hierarchical, single-factor model of depression had
      the best fit for the original full form and the Rasch-derived short form of the
      CES-D. This finding challenges depression researchers and theorists to reconsider
      the interfactor relationships in the study and assessment of depression.

PMID- 15584796
TI  - Development and preliminary validation of the physiological hyperarousal scale
      for children.
AB  - Considerable empirical support exists for the positive affect and negative affect
      components of the tripartite model of anxiety and depression proposed by L. A.
      Clark and D. Watson (1991); however, less attention has been paid to the
      physiological hyperarousal component of the model. The development of the
      Physiological Hyperarousal Scale for Children (PH-C; J. Laurent, S. J. Catanzaro,
      & T. E. Joiner Jr., 1995) is described. The psychometric properties of items are
      examined using students in Grades 6-12 (N = 398). Initial scale validation
      includes a joint factor analysis with the Positive and Negative Affect Scale for
      Children (PANAS-C; J. Laurent et al., 1999; J. Laurent, K. Potter, & S. J.
      Catanzaro, 1994). The relationship between the PH-C and existing measures that
      tap related constructs is examined. Together, the PH-C and PANAS-C provide a
      means to assess tripartite model constructs useful in differentiating anxiety and
      depression.

PMID- 15584797
TI  - Spanish-language measures of mania and depression.
AB  - Efforts to better understand bipolar spectrum disorders across ethnic groups are
      often hampered by the lack of commonly used self-report instruments to assess
      mania and depression in individuals who speak languages other than English. This
      article describes the translation into Spanish of 2 self-report measures of manic
      symptoms (i.e., the Internal State Scale and the Hypomanic Personality Scale) and
      2 self-report measures of depression (i.e., the Inventory to Diagnose Depression
      and the Inventory to Diagnose Depression, Lifetime version). The authors
      translated these measures into Spanish and assessed their psychometric properties
      among bilingual college students (N = 88). Results suggest that the Spanish
      versions have psychometric properties comparable to the English versions of the
      instruments.

PMID- 15584798
TI  - Psychometric evaluation of the parent situation inventory: a role-play measure of
      coping in parents of substance-using adolescents.
AB  - This article reports on the generalizability, reliability, and construct validity
      of the Parent Situation Inventory (PSI), a role-play measure of coping skills in
      parents experiencing problems from an adolescent's drug and alcohol use.
      Generalizability was robust (.80) and alternate form and test-retest reliability
      were satisfactory. PSI skillfulness was negatively related to the parent's own
      substance use and to the adolescent's alcohol use. The PSI shows promise as a
      reliable and potentially valid measure of coping in this population and has
      direct implications for developing and evaluating skill-based parent training
      programs.

PMID- 15584799
TI  - Revisiting the factor structure of the questionnaire on smoking urges.
AB  - This study assessed the factor structure of the Questionnaire on Smoking Urges
      (QSU), a commonly used assessment of cravings for cigarettes, with a sample of
      smokers presenting for treatment in a smoking cessation trial. On the basis of
      previous research, three confirmatory factor analytic models were tested. Model 1
      hypothesized a 26-item, 2-factor model using the items reported in the original
      QSU analysis by S. T. Tiffany and D. J. Drobes (1991). Model 2 hypothesized a 12
      item, 2-factor model comprised of the 6 most robust items found in each of the 2
      factors of the original factor analysis. Using the 12 items from Model 2, Model 3
      hypothesized a 12-item, 1-factor model. The 2nd model was found to fit the data
      best. Reliability was also tested using values obtained in this 2nd model, and
      these estimates were found to be reasonably good. Future research directions for
      the QSU are discussed.

PMID- 15584800
TI  - Furthering the use of the strengths and difficulties questionnaire: reliability
      with younger child respondents.
AB  - A sample of 917 children, aged 7 to 17 years, their parents, and their teachers
      each completed the appropriate version of the Strengths and Difficulties
      Questionnaire (SDQ), and 120 from each group did so again 2 weeks later. The
      results indicate that the SDQ demonstrates sound interinformant and test-retest
      reliability. Younger children, whose self-reports have not been assessed in
      previous studies, were reliable in their responding, although not as reliable as
      older children by these measures. However, the internal reliability of the
      various subscales, in particular, the peer problems subscale, is questionable for
      both older and younger child respondents. Overall the findings suggest that the
      SDQ's use may be extended cautiously to include self-report from younger
      children.

PMID- 15584801
TI  - Development of a brief questionnaire of smoking urges--Spanish.
AB  - Using 2 different samples of smokers, the authors developed and cross-validated a
      Spanish, brief version of the Questionnaire of Smoking Urges (QSU; S. T. Tiffany
      & D. J. Drobes, 1991). The smokers in Study 1 (N = 245) and Study 2 (N = 225)
      were from the province of Alicante, Spain. In both samples, a 2-factor model
      provided an excellent fit for a 10-item, all positively worded version of the
      QSU. Moreover, in both studies each factor uniquely contributed to predict
      nicotine dependence. Overall, there was clear evidence of construct validity for
      the multidimensionality of smoking cravings among Spanish smokers.

PMID- 15584802
TI  - Negative compatibility or object updating? A cautionary tale of mask-dependent
      priming.
AB  - The negative compatibility effect (NCE) is the surprising result that visual
      targets that follow a brief prime stimulus and a mask can be identified more
      rapidly when they are opposite rather than identical to the prime. In a recent
      article in this journal, S. T. Klapp and L. B. Hinkley (2002) proposed that this
      reflected a competition between inhibitory unconscious processes and excitatory
      conscious processes. The authors of the current article report 7 experiments with
      results countering this theory and propose an alternative account within the
      framework of object substitution masking. In this account, the NCE reflects the
      updating of perceptual objects, including their links to responses closely
      associated with those objects.

PMID- 15584803
TI  - Qualitative differences between conscious and nonconscious processing? On inverse
      priming induced by masked arrows.
AB  - In general, both consciously and unconsciously perceived stimuli facilitate
      responses to following similar stimuli. However, masked arrows delay responses to
      following arrows. This inverse priming has been ascribed to inhibition of
      premature motor activation, more recently even to special processing of
      nonconsciously perceived material. Here, inverse priming depended on particular
      masks, was insensitive to contextual requirements for increased inhibition, and
      was constant across response speeds. Putative signs of motor inhibition in the
      electroencephalogram may as well reflect activation of the opposite response.
      Consequently, rather than profiting from inhibition of primed responses, the
      alternative response is directly primed by perceptual interactions of primes and
      masks. Thus there is no need to assume separate pathways for nonconscious and
      conscious processing.

PMID- 15584804
TI  - Orienting attention via observed gaze shift evokes longer term inhibitory
      effects: implications for social interactions, attention, and memory.
AB  - One component of successful social interactions is joint attention. It is now
      well established that when a gaze shift is observed, the observer's attention
      rapidly and automatically orients to the same location in space. It is also
      established that such attention shifts via gaze are relatively transient and do
      not evoke subsequent inhibition processes. In contrast to this conventional view,
      the authors conducted a series of studies that showed that these properties of
      gaze attention shift are not necessarily the case in all situations. The article
      demonstrates (a) gaze cuing over longer intervals than previously observed, (b)
      that these longer term effects can be inhibitory, and (c) that the longer term
      gaze cuing effects do not appear to be contingent on retrieval associated with a
      particular face identity.

PMID- 15584805
TI  - Schematic influences on category learning and recognition memory.
AB  - The results from 3 category learning experiments suggest that items are better
      remembered when they violate a salient knowledge structure such as a rule. The
      more salient the knowledge structure, the stronger the memory for deviant items.
      The effect of learning errors on subsequent recognition appears to be mediated
      through the imposed knowledge structure. The recognition advantage for deviant
      items extends to unsupervised learning situations. Exemplar-based and hypothesis
      testing models cannot account for these results. The authors propose a clustering
      account in which deviant items are better remembered because they are
      differentiated from clusters that capture regularities. The function of clusters
      is akin to that of schemas. Their results and analyses expose connections among
      research in category learning, schemas, stereotypes, and analogy.

PMID- 15584806
TI  - The development of color categories in two languages: a longitudinal study.
AB  - This study unites investigations into the linguistic relativity of color
      categories with research on children's category acquisition. Naming,
      comprehension, and memory for colors were tracked in 2 populations over a 3-year
      period. Children from a seminomadic equatorial African culture, whose language
      contains 5 color terms, were compared with a group of English children. Despite
      differences in visual environment, language, and education, they showed similar
      patterns of term acquisition. Both groups acquired color vocabulary slowly and
      with great individual variation. Those knowing no color terms made recognition
      errors based on perceptual distance, and the influence of naming on memory
      increased with age. An initial perceptually driven color continuum appears to be
      progressively organized into sets appropriate to each culture and language.

PMID- 15584807
TI  - Learning nonadjacent dependencies: no need for algebraic-like computations.
AB  - Is it possible to learn the relation between 2 nonadjacent events? M. Pena, L. L.
      Bonatti, M. Nespor, and J. Mehler (2002) claimed this to be possible, but only in
      conditions suggesting the involvement of algebraic-like computations. The present
      article reports simulation studies and experimental data showing that the
      observations on which Pena et al. grounded their reasoning were flawed by deep
      methodological inadequacies. When the invalid data are set aside, the available
      evidence fits exactly with the predictions of a theory relying on ubiquitous
      associative mechanisms. Because nonadjacent dependencies are frequent in natural
      language, this reappraisal has far-reaching implications for the current debate
      on the need for rule-based computations in human adaptation to complex
      structures.

PMID- 15584808
TI  - More on the fragility of performance: choking under pressure in mathematical
      problem solving.
AB  - In 3 experiments, the authors examined mathematical problem solving performance
      under pressure. In Experiment 1, pressure harmed performance on only unpracticed
      problems with heavy working memory demands. In Experiment 2, such high-demand
      problems were practiced until their answers were directly retrieved from memory.
      This eliminated choking under pressure. Experiment 3 dissociated practice on
      particular problems from practice on the solution algorithm by imposing a high
      pressure test on problems practiced 1, 2, or 50 times each. Infrequently
      practiced high-demand problems were still performed poorly under pressure,
      whereas problems practiced 50 times each were not. These findings support
      distraction theories of choking in math, which contrasts with considerable
      evidence for explicit monitoring theories of choking in sensorimotor skills. This
      contrast suggests a skill taxonomy based on real-time control structures.

PMID- 15584809
TI  - Assessing the causal structure of function.
AB  - Theories typically emphasize affordances or intentions as the primary determinant
      of an object's perceived function. The HIPE theory assumes that people integrate
      both into causal models that produce functional attributions. In these models, an
      object's physical structure and an agent's action specify an affordance jointly,
      constituting the immediate causes of a perceived function. The object's design
      history and an agent's goal in using it constitute distant causes. When specified
      fully, the immediate causes are sufficient for determining the perceived function
      -distant causes have no effect (the causal proximity principle). When the
      immediate causes are ambiguous or unknown, distant causes produce inferences
      about the immediate causes, thereby affecting functional attributions indirectly
      (the causal updating principle). Seven experiments supported HIPE's predictions.

PMID- 15584810
TI  - Partition-edit-count: naive extensional reasoning in judgment of conditional
      probability.
AB  - The authors provide evidence that people typically evaluate conditional
      probabilities by subjectively partitioning the sample space into n
      interchangeable events, editing out events that can be eliminated on the basis of
      conditioning information, counting remaining events, then reporting probabilities
      as a ratio of the number of focal to total events. Participants' responses to
      conditional probability problems were influenced by irrelevant information (Study
      1), small variations in problem wording (Study 2), and grouping of events (Study
      3), as predicted by the partition-edit-count model. Informal protocol analysis
      also supports the authors' interpretation. A 4th study extends this account from
      situations where events are treated as interchangeable (chance and ignorance) to
      situations where participants have information they can use to distinguish among
      events (uncertainty).

PMID- 15584811
TI  - Predicting one's own forgetting: the role of experience-based and theory-based
      processes.
AB  - The authors examined the hypothesis that judgments of learning (JOL), if governed
      by processing fluency during encoding, should be insensitive to the anticipated
      retention interval. Indeed, neither item-by-item nor aggregate JOLs exhibited
      "forgetting" unless participants were asked to estimate recall rates for several
      different retention intervals, in which case their estimates mimicked closely
      actual recall rates. These results and others reported suggest that participants
      can access their knowledge about forgetting but only when theory-based
      predictions are made, and then only when the notion of forgetting is accentuated
      either by manipulating retention interval within individuals or by framing recall
      predictions in terms of forgetting rather than remembering. The authors interpret
      their findings in terms of the distinction between experience-based and theory
      based JOLs.

PMID- 15584812
TI  - Effects of task relevance and stimulus-driven salience in feature-search mode.
AB  - Attentional allocation in feature-search mode (W. F. Bacon & H. E. Egeth, 1994)
      is thought to be solely determined by top-down factors, with no role for stimulus
      driven salience. The authors reassessed this conclusion using variants of the
      spatial cuing and rapid serial visual presentation paradigms developed by C. L.
      Folk and colleagues (C. L. Folk, R. W. Remington, & J. C. Johnston, 1992; C. L.
      Folk, A. B. Leber, & H. E. Egeth, 2002). They found that (a) a nonsingleton
      distractor that possesses the target feature produces attentional capture, (b)
      such capture is modulated by bottom-up salience, and (c) resistance to capture by
      irrelevant singletons is mediated by inhibitory processes. These results extend
      the role of top-down factors in search for a nonsingleton target while arguing
      against the notion that effects of bottom-up salience and top-down factors on
      attentional priority are strictly encapsulated within distinct search modes.

PMID- 15584813
TI  - Stabilization and destabilization of perception--action patterns influence the
      self-organized recruitment of degrees of freedom.
AB  - The recruitment of an additional biomechanical degree of freedom in a unimanual
      rhythmic task was explored. Subjects were asked to synchronize adduction or
      abduction of their right index finger with a metronome, the frequency of which
      was increased systematically. In addition, haptic contact on or off the metronome
      beat was provided. Results showed that the pattern exhibiting the highest
      intrinsic stability recruited the vertical plane more than did the less stable
      one. Moreover, presence and location of haptic contact modulated coordination
      stability and therefore induced changes in the recruitment of the vertical plane.
      Thus, a trade-off was shown between coordination stability on the horizontal
      plane and recruitment of the vertical one. These findings suggest that
      recruitment of degrees of freedom is governed by general principles of
      coordination dynamics.

PMID- 15584814
TI  - Response selection difficulty and asymmetrical costs of switching between tasks
      and stimuli: no evidence for an exogenous component of task-set reconfiguration.
AB  - Four task-switching experiments examined the notion of an exogenous component of
      task-set reconfiguration (i.e., a process needed to shift task set that is not
      initiated in the absence of a task-associated figuration stimulus). The authors
      varied the complexity and familiarity of stimulus-response (SR) mapping rules to
      produce differentially time-consuming reconfiguration demands. Tasks with more
      complex or less familiar rules did not display increased switch costs, given that
      stimulus repetitions were excluded from the analysis. These results do not
      support the idea of exogenous reconfiguration. Moreover, stimulus repetitions
      inflated task-switch costs and did so disproportionately for tasks with increased
      response selection difficulty, thereby demonstrating that insufficient control of
      the sequence of stimuli may yield results that mimic those predicted by exogenous
      reconfiguration accounts.

PMID- 15584815
TI  - Interactive activation in visual word recognition: constraints imposed by the
      joint effects of spatial attention and semantics.
AB  - Two lexical-decision experiments investigated the effects of semantic priming and
      stimulus intensity when target location varied and was cued by an abrupt onset.
      In Experiment 1, the spatial cue was a good predictor of target location, and in
      Experiment 2 it was not. The results indicate that word recognition processes
      were postponed until spatial attention was focused on the target and that whether
      attention further affected word recognition depended on cue validity. The joint
      effects of cue validity and priming interacted when cue validity was high but
      were additive when cue validity was low. The joint effects of stimulus intensity
      and semantic priming also varied according to cue validity (i.e., interactive
      when high and additive when low). The results are discussed in terms of their
      implications for visual word recognition, the distinction between exogenous and
      endogenous spatial attention, and how attention is affected by visual word
      recognition processes.

PMID- 15584816
TI  - Does the information content of an irrelevant source differentially affect spoken
      word recognition in younger and older adults?
AB  - To determine whether older adults find it difficult to inhibit the processing of
      irrelevant speech, the authors asked younger and older adults to listen to and
      repeat meaningless sentences (e.g., "A rose could paint a fish") when the
      perceived location of the masker (speech or noise) but not the target was
      manipulated. Separating the perceived location (but not the physical location) of
      the masker from the target speech produced a much larger improvement in
      performance when the masker was informational (2 people talking) than when the
      masker was noise. However, the size of this effect was the same for younger and
      older adults, suggesting that cognitive-level interference from an irrelevant
      source was no worse for older adults than it was for younger adults.

PMID- 15584817
TI  - Dissociating visual attention and effector selection in spatial precuing tasks.
AB  - In this study the authors tested and rejected a recent proposal that response
      precuing effects depend on the spatial extent of the precues rather than on the
      number of response choices. Moreover, the authors tested and supported the
      hypothesis that the number of effectors in the response set is an important
      determinant of spatial precuing effects. Results of 4 experiments consistently
      showed that keypress responses generated a qualitatively different pattern of
      precuing effects than did pointing and detection responses. Together, the results
      establish a strong dissociation between planning pointing responses and planning
      keypress responses and suggest that precuing effects in 1-effector and multiple
      effector visuomotor tasks are dominated by distinct and separate mechanisms,
      visual attention and effector selection, respectively.

PMID- 15584818
TI  - The strategic control of multiple routes in imitation of actions.
AB  - The aim of this study was to bring to the surface the strategic use of imitative
      processes in the context of a 2-route model: (a) direct imitation, used in
      reproducing new, meaningless actions, and (b) imitation based on stored semantic
      knowledge of familiar meaningful actions. Three experiments were carried out with
      healthy participants who reproduced meaningful and meaningless actions within an
      established time limit. The study investigated 3 factors that could potentially
      affect the selection of processes used for imitation: (a) the composition of the
      experimental list (blocked or mixed presentation), (b) the presence-absence of
      instructions (Experiments 1 and 2), and (c) the relative proportions of the
      stimuli (Experiment 3). Overall, the results suggest that each of these factors
      influences the selection of imitative strategies in healthy individuals with
      temporarily reduced capacities, as happens in the case of brain-damaged patients.

PMID- 15584819
TI  - Stimulus processing constraints in audition.
AB  - In 3 experiments, the authors tested performance in simple tone matching and
      classification tasks. Each tone was defined on location and frequency dimensions.
      In the first 2 experiments, participants completed a same-different matching task
      on the basis of one of these dimensions while attempting to ignore irrelevant
      variation in the other dimension. In Experiment 3, in which the tones were
      classified either by frequency or location, the authors explored intertrial
      repetition effects. The patterns of performance across these different tasks were
      remarkably similar and were taken to reveal basic characteristics of stimulus
      encoding processes. The data suggest a processing sequence in audition that
      reveals an early stage in which location and frequency are treated as being
      integral and a latter stage in which location and frequency are separable.

PMID- 15584820
TI  - Panoramic search: the interaction of memory and vision in search through a
      familiar scene.
AB  - How do observers search through familiar scenes? A novel panoramic search method
      is used to study the interaction of memory and vision in natural search behavior.
      In panoramic search, observers see part of an unchanging scene larger than their
      current field of view. A target object can be visible, present in the display but
      hidden from view, or absent. Visual search efficiency does not change after
      hundreds of trials through an unchanging scene (Experiment 1). Memory search, in
      contrast, begins inefficiently but becomes efficient with practice. Given a
      choice between vision and memory, observers choose vision (Experiments 2 and 3).
      However, if forced to use their memory on some trials, they learn to use memory
      on all trials, even when reliable visual information remains available
      (Experiment 4). The results suggest that observers make a pragmatic choice
      between vision and memory, with a strong bias toward visual search even for
      memorized stimuli.

PMID- 15584821
TI  - Psychological treatments.
AB  - Psychology has recently identified itself as a health care profession and
      codified this change in the bylaws of the American Psychological Association.
      Although psychologists make a number of contributions to the nation's health--and
      mental health--the most identifiable activity focuses on treating physical or
      psychological pathology with psychological interventions. Recently, health care
      policymakers have established that evidence supporting the efficacy of these
      interventions is more than sufficient for their inclusion in health care systems
      around the world. To promote faster and more widespread dissemination of these
      interventions specifically targeting problems severe enough to be included in
      health care systems and to solidify the identification of psychology as a health
      care profession, perhaps it is time for a change in terminology. It is proposed
      that psychologists label these procedures psychological treatments so as to
      differentiate them from more generic psychotherapy, which is often used outside
      of the scope of health care systems.

PMID- 15584822
TI  - Variability discrimination in humans and animals: implications for adaptive
      action.
AB  - Both humans and animals live in a rich world of events. Some events repeat
      themselves, whereas others constantly change. The authors propose that
      discriminating this stability, sameness, and uniformity from change,
      differentness, and diversity is fundamental to adaptive action. Evidence from
      many areas of behavioral science indicates that the discrimination of and
      preference for stimulus variability affects both human and animal action. Recent
      comparative research with humans and animals illustrates a promising approach to
      the study of these issues. Discovering and understanding the behavioral and
      neural processes related to stimulus variability and its consequences for
      behavior offer distinctive challenges and important new opportunities for
      psychologists and neuroscientists.

PMID- 15584823
TI  - Reinforced variability in animals and people: implications for adaptive action.
AB  - Although reinforcement often leads to repetitive, even stereotyped responding,
      that is not a necessary outcome. When it depends on variations, reinforcement
      results in responding that is diverse, novel, indeed unpredictable, with
      distributions sometimes approaching those of a random process. This article
      reviews evidence for the powerful and precise control by reinforcement over
      behavioral variability, evidence obtained from human and animal-model studies,
      and implications of such control. For example, reinforcement of variability
      facilitates learning of complex new responses, aids problem solving, and may
      contribute to creativity. Depression and autism are characterized by abnormally
      repetitive behaviors, but individuals afflicted with such psychopathologies can
      learn to vary their behaviors when reinforced for so doing. And reinforced
      variability may help to solve a basic puzzle concerning the nature of voluntary
      action.

PMID- 15584827
TI  - Seymour Wapner (1917-2003).

PMID- 15584828
TI  - Martin Rochlin (1928-2003).

PMID- 15584829
TI  - George McRuer Guthrie (1924-2004).

PMID- 15584830
TI  - Paul Vincent Gump (1920-2003).

PMID- 15584831
TI  - Benjamin Shimberg (1918-2003).

PMID- 15584833
TI  - Effects of task autonomy on performance: an extended model considering
      motivational, informational, and structural mechanisms.
AB  - A model explaining the relationship between task autonomy and performance is
      proposed that incorporates 3 different causal mechanisms. The performance
      benefits of task autonomy may be realized by increased motivation (motivational
      mechanisms), by capitalization of information asymmetries (informational
      mechanisms), or by better alignment with task and organizational structures
      (structural mechanisms). Further, it is proposed that these performance benefits
      are moderated by a variety of variables ranging from individual traits to
      organizational design. This model may provide a means for accounting for the
      sometimes inconsistent findings in the empirical literature exploring the
      relationship between autonomy and performance. The model also offers guidance in
      the search for additional boundary conditions as well as prescriptive guidelines
      for the allocation of autonomy in practice.

PMID- 15584834
TI  - Considering rational self-interest as a disposition: organizational implications
      of other orientation.
AB  - In contrast with major theories of attitudes and behavior, the authors propose
      that individuals are not equally motivated to pursue their self-interests. The
      authors show that differences in other orientation affect the extent to which
      actions and attitudes reflect self-interested calculation (instrumental
      rationality) and the extent to which beliefs represent their external environment
      (epistemic rationality). These differences have consequences for processes
      underlying a wide range of attitudes and behavior typically assumed to be
      rationally self-interested. Thus, the authors' model exposes a common explanation
      for diverse organizational phenomena. It also clarifies inconsistencies
      surrounding the validity of certain attitudinal and motivational models, the
      relationship between job attitudes and actions, cross-cultural differences in
      attitudes and behavior, escalation of commitment, and the relationship between
      chief executive officer characteristics and organizational performance.

PMID- 15584835
TI  - Organizational citizenship behavior in work groups: a group norms approach.
AB  - Although the relationship between unit-level organizational citizenship behavior
      (OCB) and unit outcomes has been well established in recent years, the conceptual
      development of OCB at the unit level of analysis has not been adequately
      addressed. In an effort to fill this conceptual gap and to spur future research,
      the authors apply the literature on group norms to the concept of OCB. The
      resulting framework suggests a cyclical relationship between individual- and
      group-level processes and ultimately offers an explanation for how OCB norms are
      established and maintained in work groups. The authors demonstrate how this
      framework incorporates past research on the relationship between unit-level OCB
      and unit outcomes and how it extends previous research by suggesting multiple
      directions for future efforts related to unit-level OCB.

PMID- 15584836
TI  - Managing team interpersonal processes through technology: a task-technology fit
      perspective.
AB  - This article addresses the broad question, How can virtual teams that manage a
      majority of their interactions through information and communication technologies
      (ICTs) be made more effective? Focusing specifically on interpersonal
      interactions, the task-technology fit paradigm is used as the foundation for a
      theoretical model that seeks to identify how such teams can match available
      communication technologies to the different types of interpersonal interactions
      in which they engage. The authors draw on media synchronicity theory to identify
      the functionalities of the wide range of ICTs available today, and map these
      functionalities onto the salient communication needs of 3 key interpersonal
      processes: (a) conflict management, (b) motivation and confidence building, and
      (c) affect management. The model also incorporates a temporal dimension examining
      how the communication needs, and hence, the need for ICT functionality, varies
      depending on the virtual team's developmental stage. Opportunities for future
      research arising from the theoretical model are discussed.

PMID- 15584837
TI  - Employee commitment and motivation: a conceptual analysis and integrative model.
AB  - Theorists and researchers interested in employee commitment and motivation have
      not made optimal use of each other's work. Commitment researchers seldom address
      the motivational processes through which commitment affects behavior, and
      motivation researchers have not recognized important distinctions in the forms,
      foci, and bases of commitment. To encourage greater cross-fertilization, the
      authors present an integrative framework in which commitment is presented as one
      of several energizing forces for motivated behavior. E. A. Locke's (1997) model
      of the work motivation process and J. P. Meyer and L. Herscovitch's (2001) model
      of workplace commitments serve as the foundation for the development of this new
      framework. To facilitate the merger, a new concept, goal regulation, is derived
      from self-determination theory (E. L. Deci & R. M. Ryan, 1985) and regulatory
      focus theory (E. I. Higgins, 1997). By including goal regulation, it is
      acknowledged that motivated behavior can be accompanied by different mindsets
      that have particularly important implications for the explanation and prediction
      of discretionary work behavior.

PMID- 15584838
TI  - Work group diversity and group performance: an integrative model and research
      agenda.
AB  - Research on the relationship between work group diversity and performance has
      yielded inconsistent results. To address this problem, the authors propose the
      categorization-elaboration model (CEM), which reconceptualizes and integrates
      information/decision making and social categorization perspectives on work-group
      diversity and performance. The CEM incorporates mediator and moderator variables
      that typically have been ignored in diversity research and incorporates the view
      that information/decision making and social categorization processes interact
      such that intergroup biases flowing from social categorization disrupt the
      elaboration (in-depth processing) of task-relevant information and perspectives.
      In addition, the authors propose that attempts to link the positive and negative
      effects of diversity to specific types of diversity should be abandoned in favor
      of the assumption that all dimensions of diversity may have positive as well as
      negative effects. The ways in which these propositions may set the agenda for
      future research in diversity are discussed.

PMID- 15584839
TI  - A relational model of workplace victimization: social roles and patterns of
      victimization in dyadic relationships.
AB  - This article proposes a model of the ways in which dyadic interactions between
      employees who occupy 1 of 4 archetypal social roles in organizations can lead to
      either episodic or institutionalized patterns of victimization. The model shows
      how the occurrence of victimization involving these 4 role types is influenced by
      organizational variables such as power differences, culture, and access to social
      capital. The model integrates behavioral and social structural antecedents of
      victimization to develop a relational perspective on the dynamics of harmful
      behavior in the workplace.

PMID- 15584840
TI  - A multiple-goal, multilevel model of feedback effects on the regulation of
      individual and team performance.
AB  - When working as a member of a team, individuals must make decisions concerning
      the allocation of resources (e.g., effort) toward individual goals and team
      goals. As a result, individual and team goals, and feedback related to progress
      toward these goals, should be potent levers for affecting resource allocation
      decisions. This research develops a multilevel, multiple-goal model of individual
      and team regulatory processes that affect the allocation of resources across
      individual and team goals resulting in individual and team performance. On the
      basis of this model, predictions concerning the impact of individual and team
      performance feedback are examined empirically to evaluate the model and to
      understand the influence of feedback on regulatory processes and resource
      allocation. Two hundred thirty-seven participants were randomly formed into 79
      teams of 3 that performed a simulated radar task that required teamwork. Results
      support the model and the predicted role of feedback in affecting the allocation
      of resources when individuals strive to accomplish both individual and team
      goals.

PMID- 15584841
TI  - A covariance structure analysis of employees' response to performance feedback.
AB  - This longitudinal study used D. R. Ilgen, C. D. Fisher, and M. S. Taylor's (1979)
      feedback process model as a theoretical framework to determine whether a
      sequential chain of cognitive variables mediates an individual's response to
      performance feedback. One hundred two employees were surveyed 2 weeks after their
      performance appraisal, and performance was assessed 11 months later at the end of
      the review cycle. Covariance structure analysis supported the convergent and
      discriminant validity of the constructs underlying the model and the
      constellation of structural relationships. A set of cognitive variables was found
      to completely mediate the relationship between an individual's receipt and
      response to feedback. Implications for the feedback process and future research
      are discussed.

PMID- 15584842
TI  - Measurement equivalence of the German Job Satisfaction Survey used in a
      multinational organization: implications of Schwartz's culture model.
AB  - The authors tested measurement equivalence of the German Job Satisfaction Survey
      (GJSS) using structural equation modeling methodology. Employees from 18
      countries and areas provided data on 5 job satisfaction facets. The effects of
      language and culture on measurement equivalence were examined. A cultural
      distance hypothesis, based on S. H. Schwartz's (1999) theory, was tested with 4
      cultural groups: West Europe, English speaking, Latin America, and Far East.
      Findings indicated the robustness of the GJSS in terms of measurement equivalence
      across countries. The survey maintained high transportability across countries
      speaking the same language and countries sharing similar cultural backgrounds.
      Consistent with Schwartz's model, a cultural distance effect on scale
      transportability among scales used in maximally dissimilar cultures was detected.
      Scales used in the West Europe group showed greater equivalence to scales used in
      the English-speaking and Latin America groups than scales used in the Far East
      group.

PMID- 15584843
TI  - The outcomes and correlates of job search objectives: searching to leave or
      searching for leverage?
AB  - The authors investigate a previously overlooked yet important objective for
      employee job search--seeking leverage against the current employer. They explore
      the outcomes and correlates of leverage-seeking search and how it may differ from
      the more traditional objective for engaging in job search--to change jobs.
      Results show that leverage-seeking and separation-seeking search objectives
      associate with different outcomes. The authors also find that characteristics of
      the work situation and individual differences associate with leverage-seeking
      search and relate differently with the 2 job search objectives. Implications for
      practice and the advancement of job search research are discussed.

PMID- 15584844
TI  - The effect of feedback sign on task performance depends on self-concept
      discrepancies.
AB  - Control theories claim that information about performance is often used by
      multiple goal systems. A proposition tested here was that performance information
      can create discrepancies in self-concept goals, directing cognitive resources
      away from the task goal system. To manipulate performance information, 160
      undergraduates were given false positive or false negative normative feedback
      while working on a task that did or did not require substantial cognitive
      resources. Half of the participants were then given an opportunity to reaffirm
      their self-concepts following feedback, whereas half were not. Feedback sign
      positively related to performance only for those working on the cognitively
      intense task and not given a chance to reaffirm. Otherwise, feedback sign was
      negatively related to performance, albeit weakly.

PMID- 15584845
TI  - Comparison of polygraph data obtained from individuals involved in mock crimes
      and actual criminal investigations.
AB  - In a preliminary attempt to determine the generalizability of data from
      laboratory mock-crime studies, the authors examined the similarities and
      differences among the cardiovascular, electrodermal, and respiration responses of
      deceptive and nondeceptive individuals elicited to crime-relevant and crime
      irrelevant questions. Participants in the laboratory group were randomly assigned
      to nondeceptive (n = 28) or deceptive (n = 27) treatment groups, and a mock-crime
      scenario was used. The field participants were confirmed nondeceptive (n = 28) or
      deceptive (n = 39) criminal suspects who underwent polygraph examinations between
      1993 and 1997. The results indicated that there were salient differences between
      field and similarly obtained laboratory polygraph response measures. However,
      accuracy of laboratory participants' classifications using logistic regression
      analysis was not significantly different from field participants' classification
      accuracy.

PMID- 15584846
TI  - Effects of administrator-witness contact on eyewitness identification accuracy.
AB  - Concern that lineup administrators can influence eyewitness identifications has
      led researchers to suggest implementing double-blind testing, an idea that police
      resist. Using a typical eyewitness paradigm (video event followed by photographic
      identification test), the present study demonstrated that an alternative
      technique, minimizing the level of contact between lineup administrators and
      witnesses, could reduce false identifications without reducing hits.
      Specifically, witnesses were more likely to make decisions consistent with lineup
      administrator expectations when the level of contact between the administrator
      and the witness was high than when it was low. These results are explained within
      the experimenter expectancy framework. Implications for applied settings are
      discussed.

PMID- 15584847
TI  - Morbidity associated with the management of rectal cancer and its impact on
      patient quality of life.

PMID- 15584848
TI  - Study of factors related to quality of life in patients with locally advanced
      rectal cancer.
AB  - OBJECTIVES: Given the increasing concern about the physical, psychological, and
      social welfare of patients surgically treated for rectal cancer, we designed a
      study of the factors influencing quality of life in these patients. EXPERIMENTAL
      DESIGN: We prospectively analyzed factors related to quality of life in a cohort
      of patients using the Nottingham Health Profile and the EORTC questionnaire (QLQ
      CR 38). PATIENTS: A total of 116 patients with locally advanced rectal cancer
      surgically treated in our hospital from 1994 to 1999. RESULTS: Quality of life
      scores for the various factors studied showed that quality of life was worse in
      women, in patients with tumors in the middle third of the rectum, and in patients
      undergoing low anterior resection. CONCLUSIONS: Factors influencing quality of
      life in patients surgically treated for locally advanced rectal cancer included
      sex, tumor site, and surgical technique. Since only this latter factor is
      modifiable, we suggest that the surgical technique be individualized in persons
      with mid-lower and lower-third tumors of the rectum, bearing in mind that quality
      of life in amputated patients is, in many respects, better than that of patients
      with preserved sphincters.

PMID- 15584849
TI  - Efficacy and safety of argon plasma coagulation for the treatment of hemorrhagic
      radiation proctitis.
AB  - OBJECTIVE: To evaluate the efficacy, safety and medium-/long-term clinical course
      of patients undergoing endoscopic treatment with argon plasma coagulation for
      hemorrhagic radiation proctopathy. DESIGN: Descriptive, retrospective study with
      medium- and long-term follow-up. PATIENTS, MATERIAL AND METHODS: Ten patients
      were treated with argon plasma coagulation for hemorrhagic radiation proctopathy
      between July 1998 and February 2003. Inclusion criteria were: evidence of chronic
      rectal bleeding, consistent endoscopic findings, and absence of any other cause
      of hematochezia after a comprehensive ano-rectal examination and complete
      colonoscopy. The equipment used was a standard colonoscope, an argon delivery
      unit, an argon plasma coagulation probe 1.5 mm in internal diameter, and a high
      frequency electrosurgical generator. Consecutive treatment sessions were
      programmed whenever it was considered necessary until all mucosal lesions had
      been treated. Clinical and evolutive follow-up was performed with a focus on
      tolerance, efficacy, and potential argon plasma coagulation-related
      complications. Data were updated by personal or telephonic interview. RESULTS: In
      all patients, chronic rectal bleeding stopped after the last treatment session.
      The mean number of treatment sessions to stop symptoms was 1.7. Mean follow-up
      was 31.1 months. All sessions were well tolerated, similarly to standard
      rectoscopy. In one case a recurrence of rectal bleeding was observed four months
      later, which required two repeat sessions. Four patients were anemic at
      inclusion. Three of them reported a resolved anemia at the end of the study. No
      delayed argon plasma coagulation-related complications such us ulcers or
      strictures were seen. CONCLUSIONS: Argon plasma coagulation appears to be a
      useful, effective and safe treatment for rectal bleeding resulting from chronic
      radiation proctitis when compared to standard medical and endoscopic treatments.
      These successful outcomes seem to persist even after long-term follow-up.

PMID- 15584850
TI  - Postoperative radiotherapy-induced morbidity in rectal cancer.
AB  - OBJECTIVES: We analyzed long-term morbidity and bowel function alteration after
      postoperative radiotherapy for rectal cancer following resection with
      anastomosis. PATIENTS AND METHODS: Thirty-seven patients who underwent surgery
      with intention to cure and a minimal follow-up period of 3 years were included.
      These patients were divided into two groups: in the first group, 14 patients
      received postoperative chemo-radiotherapy, 5-fluorouracil plus folinic acid, and
      45 Gy plus 5 Gy boost. In the second group, there were 23 patients regarded as
      controls. We designed a questionnaire about their bowel function and analyzed the
      morbidity detected in their follow-up. RESULTS: The group that was treated with
      postoperative chemo-radiotherapy had more daily bowel movements (p = 0.03) and
      night-time movements (p = 0.04); incontinence (69.2 vs. 17.4% in the control
      group; p = 0.002), and perianal skin irritation (p = 0.04) versus the control
      group. Although without meaningful differences, the group under treatment wore a
      pad more often, had more defecatory urgency, could distinguish worse gas from
      stool, and needed more frequently antidiarrheal measures. Major complications
      were present in 28.6% of the under-treatment group: three intestinal resections
      were performed due to actinic stenosis; one patient had a residual stercoral
      fistula; another had several occlusive crises solved with medical treatment.
      CONCLUSIONS: Postoperative chemo-radiotherapy had a high morbidity rate, which
      determined a significant alteration in quality of life. Accuracy in indication is
      therefore necessary, as well as a consideration of other alternatives for
      treatment, such as preoperative chemo-radiotherapy and total mesorectal excision.

PMID- 15584851
TI  - Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy
      volunteers.
AB  - OBJECTIVES: To assess the salivary flow rate, pH, and buffer capacity of healthy
      volunteers, and their relationships with age, gender, obesity, smoking, and
      alcohol consumption, and to establish the lower-end value of normal salivary flow
      (oligosialia). METHODS: A prospective study was conducted in 159 healthy
      volunteers (age > 18 years, absence of medical conditions that could decrease
      salivary flow). Unstimulated whole saliva was collected during ten minutes, and
      salivary flow rate (ml/min), pH, and bicarbonate concentration (mmol/l) were
      measured using a Radiometer ABL 520. The 5 percentile of salivary flow rate and
      bicarbonate concentration was considered the lower limit of normality. RESULTS:
      Median salivary flow rate was 0.48 ml/min (range: 0.1-2 ml/min). Age younger than
      44 years was associated with higher flow rates (OR 2.10). Compared with women,
      men presented a higher flow rate (OR 3.19) and buffer capacity (OR 2.81).
      Bicarbonate concentration correlated with salivary flow rate. The lower-end
      values of normal flow rate and bicarbonate concentration were 0.15 ml/min and
      1.800 mmol/l, respectively. The presence of obesity, smoking, and alcohol
      consumption did not influence salivary parameters. CONCLUSIONS: In healthy
      volunteers, salivary flow rate depends on age and gender, and correlates with
      buffer capacity. Obesity, smoking, and alcohol use do not influence salivary
      secretion.

PMID- 15584852
TI  - Pancreatic cancer. Management.
AB  - Pancreatic cancer still represents a serious medical concern for which no
      adequate solution has thus far been found. Surgery is the only appropriate
      therapy, but has a survival rate of around 30-35% at three years, with an
      operative mortality below 3% and an operative morbidity approaching 10% of
      radically resected patients, all of which applies to surgery performed by expert
      teams in highly experienced sites.

PMID- 15584853
TI  - Amebic liver abscess with bacterial superinfection in a patient with no
      epidemiologic risk factors.
AB  - The amebic liver abscess is uncommon in developed countries like Spain, but the
      incidence is increasing probably due to the migratory movements of the
      population. We report a case of an amebic abscess, initially unsuspected due to
      the absence of epidemiologic risk factors and the negative serology for
      amebiasis, in the early stages of the disease.

PMID- 15584854
TI  - Ileal ulcers in a long-distance runner diagnosed by capsule endoscopy.

PMID- 15584855
TI  - [Mesenteric lymphadenopathy in celiac disease].

PMID- 15584856
TI  - [Intestinal obstruction by mucosecretor cystadenocarcinoma in ectopic pancreas].

PMID- 15584857
TI  - Emerging technologies for the identification of therapeutic targets for the
      management of pre-eclampsia.
AB  - Pre-eclampsia is a common and serious complication of pregnancy characterised by
      hypertension and proteinuria. Genetic and environmental factors influence the
      occurrence and progression of the disease. Emerging experimental systems and
      increasingly specific analytical methods for the study of differences between
      normal and pre-eclamptic placentae are close to identifying specific indicators
      of disease, which may allow early diagnosis and intervention and reveal targets
      against which therapeutic agents can be developed.

PMID- 15584858
TI  - MRSA: status and prospects for therapy? An evaluation of key papers on the topic
      of MRSA and antibiotic resistance.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a serious nosocomial
      pathogen, and a related community-sourced MRSA is emerging. MRSA has evolved to
      become the major S. aureus phenotype in the hospital, emerging from just 30 to
      over 60% of the S. aureus population over the past 15 years. Together with its
      beta-lactam resistance, MRSA possesses multi-drug resistance genotype, including
      quinolones, macrolides and sulfonamides. MRSA has now emerged as the predominant
      nosocomial Gram-positive pathogen, and it has a high rate of mortality. Action
      must be taken to contain and eradicate MRSA through a combination of infection
      control and the development of novel anti-MRSA agents and vaccines.

PMID- 15584859
TI  - Cancer vaccines.
AB  - Cancer vaccines - a dream or a reality? There is no doubt that a time will come
      when this new approach to cancer treatment will provide opportunities that will
      be both complementary and synergistic with existing treatments. Novelty is often
      linked to risk, and if there is a given medical field that desperately needs
      therapeutic improvement, cancer is it. Recent advances on the understanding of
      the functioning and manipulation of the immune system and on the host-tumour
      relationship, and on tumour escape, will soon pay off. However, the development
      of cancer vaccines is not an easy undertaking and the multitude of obstacles are
      presented and reviewed in this article. The cancer vaccine 'detractors' that are
      arguing negatively on the chances of success are, to this date, correct.
      Nevertheless, a parallel could be drawn from the monoclonal antibodies, which
      have suffered from a long and difficult history, to hold promise in man. Recent
      technological progress has once again demonstrated that one can eventually bypass
      the commonly accepted barriers, as there are now monoclonal-based products
      currently helping patients. The entire oncology community is eagerly awaiting the
      next chapter in the cancer vaccine story.

PMID- 15584860
TI  - Therapeutic targets for antimetastatic therapy.
AB  - Metastases are responsible for most cancer deaths. Despite dramatic advances in
      cancer therapy, the presence of metastases implies a significantly shortened
      survival and reduced quality of remaining life. Aside from prevention of cancer
      altogether, or significant improvements in early detection for most cancers,
      effective novel therapeutic strategies targeting metastasis should provide the
      greatest clinical benefit. Metastasis research has shown that many of the initial
      steps in metastasis are completed with a high degree of efficiency and may have
      occurred by the time of clinical diagnosis. Therefore, targeting the later stages
      of metastasis may offer a more promising therapeutic approach for the development
      of antimetastatic therapies. Appropriate clinical strategies include targeting
      dormant solitary cells, active preangiogenic metastases, or vascularised
      metastases. Dormancy of solitary single cells, seen clinically and
      experimentally, may be an explanation for cancer recurrence. Eradication or
      inactivation of these dormant cells could provide large benefit for patients.
      However, little is known about what makes cancer cells dormant and, therefore, a
      greater knowledge of the mechanisms of dormancy is needed. This review discusses
      potential biological targets, as defined by the steps in the metastatic process,
      for antimetastatic therapies and provides examples of clinical strategies for
      preventing or treating successful metastasis.

PMID- 15584861
TI  - The complexity of PTEN: mutation, marker and potential target for therapeutic
      intervention.
AB  - Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a phosphatase
      that removes phosphates primarily from lipids. It has also been called mutated in
      multiple advanced cancers 1 and transforming growth factor-beta regulated
      epithelial cell-enriched phosphatase 1. The best described substrate of PTEN is
      phosphatidyliniositol (3,4,5)-tris-phosphate [PtdIns(3,4,5)P3]. PTEN removes the
      phosphate in PtdIns(3,4,5)P(3) to generate PtdIns(4,5)P(2). PTEN serves to
      counter-balance the effects of phosphoinositide 3' kinase, which normally adds a
      phosphate to PtdIns(4,5)P(2) to generate PtdIns(3,4,5)P(3). PtdIns(3,4,5)P(3)
      recruits kinases such as phosphoinositide-dependent kinase 1, which in turn
      phosphorylate Akt, which phosphorylates other downstream proteins involved in
      regulation of apoptosis and cell-cycle progression. PTEN removal of the phosphate
      from PtdIns(3,4,5)P(3) inhibits this pathway by preventing localisation of
      proteins with pleckstrin homology domains to the cell membrane. Alterations of
      the PTEN gene are associated with cancer and other diseases. Novel therapeutic
      approaches have been developed to counteract the deletion/mutation of PTEN in
      human cancer. This review will discuss the role of PTEN in signal transduction
      and cancer as well as pharmacological approaches to combat PTEN loss in human
      cancer.

PMID- 15584862
TI  - Therapeutic potential of target of rapamycin inhibitors.
AB  - Target of rapamycin (TOR) functions within the cell as a transducer of
      information from various sources, including growth factors, energy sensors, and
      hypoxia sensors, as well as components of the cell regulating growth and
      division. Blocking TOR function mimics amino acid, and to some extent, growth
      factor deprivation and has a cytostatic effect on proliferating cells in vivo.
      Inhibition of TOR in vivo, utilising its namesake rapamycin, leads to
      immunosuppression. This property has been exploited successfully with the use of
      rapamycin and its derivatives as a therapeutic agent in the prevention of organ
      rejection after transplantation with relatively mild side effects when compared
      to other immunosuppressive agents. The cytostatic effect of TOR on vascular
      smooth muscle cell proliferation has also recently been exploited in the
      therapeutic application of rapamycin to drug eluting stents for angioplasty.
      These stents significantly reduce the amount of arterial reblockage that results
      from proliferating vascular smooth muscle cells. In cancer, the effect of
      blocking TOR function on tumour growth and disease progression is currently of
      major interest and is the basis for a number of ongoing clinical trials. However,
      different cell types and tumours respond differently to TOR inhibition, and TOR
      is clearly not cytostatic for all types of cancer cells in vitro or in vivo. As
      the molecular details of how TOR functions and the targets of TOR activity are
      further elucidated, tumour and tissue specific functions are being identified
      that implicate TOR in angiogenesis, apoptosis, and the reversal of some forms of
      cellular transformation. This review will describe our current understanding of
      TOR function, describe the current strategies for employing TOR inhibitors in
      clinical and preclinical development, and outline future strategies for
      appropriate targets of TOR inhibitors in the treatment of disease.

PMID- 15584863
TI  - Hitting multiple targets with multimeric ligands.
AB  - Multimeric ligands consist of multiple monomeric ligands attached to a single
      backbone molecule, creating a multimer that can bind to multiple receptors or
      targets simultaneously. Numerous examples of multimeric binding exist within
      nature. Due to the multiple and simultaneous binding events, multimeric ligands
      bind with an increased affinity compared to their corresponding monomers.
      Multimeric ligands may provide opportunities in the field of drug discovery by
      providing enhanced selectivity and affinity of binding interactions, thus
      providing molecular-based targeted therapies. However, gaps in our knowledge
      currently exist regarding the quantitative measures for important design
      characteristics, such as flexibility, length and orientation of the inter-ligand
      linkers, receptor density and ligand sequence. In this review, multimeric ligand
      binding in two separate phases is examined. The prerecruitment phase describes
      the binding of one ligand of a multimer to its corresponding receptor, an event
      similar to monomeric ligand binding. This results in transient increases in the
      local concentration of the other ligands, leading to apparent cooperativity. The
      postrecruitment phase only occurs once all receptors have been aligned and bound
      by their corresponding ligand. This phase is analogous to DNA-DNA interactions in
      that the stability of the complex is derived from physical orientation. Multiple
      factors influence the kinetics and thermodynamics of multimeric binding, and
      these are discussed.

PMID- 15584864
TI  - The promise of genomics to identify novel therapeutic targets.
AB  - The cataloguing of the human genome has provided an unprecedented prospectus for
      target identification and drug discovery. A current analysis indicates that
      slightly more than 3000 unique protein encoding loci are potentially amenable to
      pharmacological intervention (the 'druggable genome', which can be queried at
      http://function.gnf.org/druggable). However, the assessment of genome sequence
      data has not resulted in the anticipated acceleration of novel therapeutic
      developments. The basis for this shortfall lies in the significant attrition
      rates endemic to preclinical/clinical development, as well as the often
      underestimated complexity of gene function in higher order biological systems. To
      address the latter issue, a number of strategies have emerged to facilitate
      genomics-driven target identification and validation, including cellular
      profiling of gene function, in silico modelling of gene networks, and systematic
      analyses of protein complexes. The expectation is that the integration of these
      and other systems-based technologies may enable the conversion of potential
      genomic targets into functionally validated molecules, and result in practicable
      gene-based drug discovery pipelines.

PMID- 15584865
TI  - NMR-based techniques in the hit identification and optimisation processes.
AB  - In this review, the use of general NMR spectroscopy techniques to detect ligand
      binding and to monitor enzyme kinetics and inhibition, which appear particularly
      useful in hit identification and validation, is reiterated. Furthermore, the use
      of NMR-based strategies for lead optimisations that are based on either iterative
      derivatisations of an initial core structure or on linking fragments that occupy
      adjacent pockets in the target's binding site will also be described. Several
      recent examples will be reported and the use of these techniques in cases when
      the three dimensional structure of the target protein is known will be discussed.

PMID- 15584866
TI  - Janus kinase 3: a novel target for selective transplant immunosupression.
AB  - Existing immunosuppressants inhibit lymphocyte activation and T cell cytokine
      signal transduction pathways, reducing the rate of acute rejection episodes to <
      10%. However, the widespread tissue distribution of their molecular targets
      engenders pleiotropic toxicities. One strategy to address this problem seeks to
      identify compounds that selectively inhibit a target restricted in distribution
      to the lymphoid system. Janus kinase (Jak) 3 is such a molecule; it mediates
      signal transduction via the gamma common chain of lymphokine surface receptors.
      Disruption of this lymphoid-restricted enzyme would not be predicted to produce
      collateral damage in other organ systems. Development of selective Jak3
      inhibitors has been difficult due to crossreactivity with its homologue, Jak2. In
      contrast to all other putative antagonists, which are discussed in detail herein,
      one Jak3 inhibitor, NC1153, shows at least 40-fold greater selective inhibition
      for Jak3 than for Jak2, is robustly synergistic with calcineurin antagonists,
      and, either alone or in combination with cyclosporin, produces no adverse effects
      in rodents preconditioned to be at heightened risk for nephrotoxicity, bone
      marrow suppression, or altered lipid metabolism.

PMID- 15584867
TI  - The search for novel antipsychotics: pharmacological and molecular targets.
AB  - There can be little doubt that the newer, atypical, antipsychotic drugs provide
      improved treatment for many patients suffering from schizophrenia. However, the
      significant gains in tolerability produced by these drugs have not generally been
      accompanied by major advances in clinical efficacy. In particular, negative and
      cognitive symptoms, which may represent the core deficit of the disease, remain
      inadequately treated. There is, therefore, a pressing need for more effective
      drugs. A number of drug discovery and development programmes are currently
      underway in parallel with significant research into the basic neurobiology of the
      disease. All antipsychotic drugs currently used in the clinic are antagonists at
      dopamine D2 receptors, and dopamine neurotransmission seems likely to remain a
      major biological target for research. However, novel approaches to modulate
      dopaminergic neurotransmission selectively in relevant brain regions may be
      required. In addition, a range of non-dopaminergic targets including glutamate,
      serotonin, neurokinins and acetylcholine are also of major interest. It is
      likely, however, that the importance of many of these targets may lie in their
      relationships to and interactions with dopaminergic mechanisms. Finally, advances
      in genetics and molecular biology are identifying genes associated with a
      susceptibility to develop schizophrenia. It remains to be seen whether or not
      these genes and their associated proteins will provide molecular targets for
      successful drug discovery.

PMID- 15584868
TI  - Clues for new therapeutics in osteoporosis and periodontal disease: new roles for
      lipoxygenases?
AB  - Lipoxygenase (LOX) pathways are well appreciated for their ability to regulate
      key events contributing to the cardinal signs of inflammation. Recent evidence
      indicates that LOX genes are associated with osteoporosis. Also, overexpression
      of the 15-LOX Type 1 in transgenic rabbits leads to a reduced inflammatory
      phenotype and protection from periodontal disease, as well as atherosclerosis.
      Osteoporosis and inflammation-associated bone degradation, such as periodontitis,
      affect many individuals worldwide and are known to have pathogenesis that
      involves local mediators via communication between osteoclasts and osteoblasts
      during osteogenesis. Evidence has emerged indicating that LOX gene expression is
      associated with reduced bone strength in murine models of osteoporosis.
      Overexpression of the 15-LOX gene and its products, such as lipoxins, confers
      endogenous anti-inflammation. This article discusses the recent findings that may
      link aberrant LOX pathway expression in these diseases, suggesting new avenues
      for therapeutic approaches via activation of endogenous pathways for resolution
      of local inflammation.

PMID- 15584869
TI  - Chemical genetics for therapeutic target mining.
AB  - Chemical genetics is an emerging research field that utilises biologically active
      small molecules to study biological functions of genes and their products. The
      direct regulation of the protein function by the biologically active small
      molecules can alternate the gene mutagenesis studies utilised in conventional
      genetics. Like conventional genetics, chemical genetics can be divided into two
      concepts - 'forward' and 'reverse' chemical genetics. These approaches of
      chemical genetics have a tremendous impact on both functional genomics and drug
      development. This review focuses on the two ways in which chemical genetics can
      be used for therapeutic target mining and their practical application in drug
      development, particularly, in angiogenesis-related diseases.

PMID- 15584870
TI  - Calstabin2 - a new target in sudden cardiac death.
AB  - Sudden cardiac death is occasionally observed in people with structurally normal
      hearts. Calstabin2 stabilises the ryanodine receptor (RyR)2, preventing aberrant
      activation of the sarcoplasmic reticulum calcium channel during the resting phase
      of the cardiac muscle. Calstabin2-deficient mice have structurally normal hearts,
      but exhibit exercise-induced cardiac ventricular arrhythmias that cause sudden
      death. In three models of arrhythmias, the calstabin2 stabiliser JTV519 did not
      prevent arrhythmias in calstabin2(-/-) mice, but reduced the arrhythmias in
      calstabin2(+/-) mice, illustrating the antiarrhythmic potential of stabilising
      calstabin2. Familial polymorphic ventricular tachycardia (FPVT) has been linked
      to three missense mutants (P2328S, Q4201R and V4653F) in the hRyR2 gene of
      Finnish families. In HEK293 cells, these RyR2 mutants showed less binding of
      (35)S-calstabin2 than the wild-type, indicating a reduced binding affinity.
      JTV519 rescues the gain-of-function defect in the RyR2-P2328S channels via
      increased binding of calstabin2 to the channel complex. In heart failure (HF),
      there is excessive disassociation of calstabin2 from the RyR2 receptor, and
      JTV519 has been shown to be beneficial in an animal model of HF. In conclusion,
      calstabin2 is an important new target in sudden cardiac death associated with
      either FPVT or HF.

PMID- 15584871
TI  - Candidate gene selection in pharmacogenomics: biology leads the way.

PMID- 15584872
TI  - Pharmacogenomics in Asia.
AB  - It is well known that genetic polymorphisms, such as SNPs, vary between races so
      that not only Western populations' pharmacogenetic/pharmacogenomic data but also
      data from Asians are viewed as vital to drug development and clinical practice.
      For this report, the current state of pharmacogenetic/pharmacogenomic-related
      activities in five Asian countries (China, Japan, the Republic of Korea,
      Singapore, and Taiwan) were researched and analyzed. The results show that there
      are multiple efforts underway in all of these countries, including the
      examination of guidelines, the implementation of projects to establish
      foundations for pharmacogenetics/pharmacogenomics, and several clinical trials,
      that have hardly been recognized up to now.

PMID- 15584874
TI  - Genotyping for drug-metabolizing enzymes--does the promise meet the reality?

PMID- 15584875
TI  - Alcoholism: genes and mechanisms.
AB  - Alcoholism is a chronic relapsing/remitting disease that is frequently
      unrecognized and untreated, in part because of the partial efficacy of treatment.
      Only approximately one-third of patients remain abstinent and one-third have
      fully relapsed 1 year after withdrawal from alcohol, with treated patients doing
      substantially better than untreated [1]. The partial effectiveness of strategies
      for prevention and treatment, and variation in clinical course and side effects,
      represent a challenge and an opportunity to better understand the neurobiology of
      addiction. The strong heritability of alcoholism suggests the existence of
      inherited functional variants of genes that alter the metabolism of alcohol and
      variants of other genes that alter the neurobiologies of reward, executive
      cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these
      neurobiologies has been identified as a critical domain in the addictions.
      Functional alleles that alter alcoholism-related intermediate phenotypes include
      common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause
      the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met
      leading to differences in three aspects of neurobiology: executive cognitive
      function, stress/anxiety response, and opioid function; opioid receptor micro1
      (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of
      naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters
      serotonin transporter function and appears to affect stress response and
      anxiety/dysphoria, which are factors relevant to initial vulnerability, the
      process of addiction, and relapse.

PMID- 15584876
TI  - Genomic characterization of Alzheimer's disease and genotype-related phenotypic
      analysis of biological markers in dementia.
AB  - More than 180 genes distributed across the human genome are potentially involved
      in the pathogenesis of Alzheimer's disease (AD). The AD population shows a higher
      genetic variation rate than the control population. Significant differences in
      allelic distribution and frequency exist when AD-related polygenic clusters are
      compared with other forms of dementia, indicating that the genetic component in
      neurodegenerative dementia differs from that of other CNS disorders. The
      characterization of AD genotype-related phenotypic profiles reveals substantial
      differences in biological markers among AD clusters associated with different
      genes and/or allelic combinations. AD and dementia with vascular component (DVC)
      are the most prevalent forms of dementia. Both clinical entities share many
      similarities, but they differ in their major phenotypic and genotypic profiles,
      as revealed by structural and functional genomics studies. Comparative phenotypic
      studies have identified significant differences in 25% of more than 100
      parametric variables, including anthropometric values, cardiovascular function,
      blood pressure, lipid metabolism, uric acid metabolism, peripheral calcium
      homeostasis, liver function, alkaline phosphatase, lactate dehydrogenase, red and
      white blood cells, regional brain atrophy, and brain blood flow velocity.
      Functional genomic studies incorporating apolipoprotein E (APOE)-related changes
      in biological markers extended the difference between AD and DVC by up to 57%.
      Structural genomic studies with AD-related genes, including APP, MAPT, APOE, PS1,
      PS2, A2M, ACE, AGT, cFOS, and PRNP, demonstrate different genetic profiles in AD
      and DVC, with an absolute genetic variation rate in the range of 30-80%,
      depending upon genes and genetic clusters. The relative polymorphic variation in
      genetic clusters integrated by two, three or four genes associated with AD ranges
      from 1 to 3%. The main phenotypic differences in AD are genotype dependent,
      indicating a powerful influence of polygenic factors on the AD phenotypic
      profile. All these genotypic and phenotypic variations bring about important
      consequences for the pharmacogenomics of AD.

PMID- 15584877
TI  - Pharmacogenetics/pharmacogenomics and antirheumatic drugs in rheumatology.
AB  - Genomic medicine has raised many expectations with regard to individualized
      therapies. Drug response is a complex function of many genes interacting with
      environmental and behavioral factors. In addition, poor prescribing, interactions
      between drugs and an incomplete understanding of the metabolism of many drugs,
      which are administered simultaneously to treat concomitant morbidities, are
      leading causes of the occurrence of adverse drug reactions in chronic non
      inflammatory and autoimmune rheumatic diseases. Symptomatic non-steroidal anti
      inflammatory drugs, as well as disease-modifying drugs, are complicated by drop
      outs (poor patient compliance) in a large percentage of patients. Even though
      intensive and careful monitoring is always clearly advisable, preliminary data
      suggest that typing of genes controlling the effects, metabolism and response of
      drugs might be of clinical utility to define the 'at-risk' genotype.

PMID- 15584878
TI  - Expression genomics and cancer biology.
AB  - Expression genomics is a term that is used to describe the investigation of
      transcription in a whole-genome manner and includes the investigation of gene
      regulation. Characteristic of this approach is its comprehensiveness and the
      highly multiplexed nature of its analysis. Thus, the range of technologies used
      include microarrays, tag library approaches, such as serial analysis of gene
      expression (SAGE), full-length cDNA cloning and sequencing, and chromatin
      immunoprecipitation coupled with cloning/sequencing or applied to genomic chips.
      These technologies are all complementary since they have different capabilities
      and attack different components of the transcriptome: transcriptional regulation,
      promoter usage, differential splicing, and gene expression. Unlike genome
      sequencing, the combinatorial complexity of the transcriptome is immense, making
      its complete characterization impossible. Instead, the strategy has shifted to
      the analysis of the whole transcriptome in a context-driven, cell biological
      framework where the fundamental truths emerge through multiple comparisons and
      pharmacological challenges. The density of non-redundant data generated with any
      experiment allows for the assessment of higher order relationships. This
      comprehensive data, in turn, permits information convergence across different
      experiments, organisms, and data sets. Surprising concordance in the underlying
      conclusions is observed with data of such complexity. Since microarrays have been
      the most widely used technology in expression genomics for the study of cancer
      biology, this paper will focus on studies using expression arrays, but will also
      touch on other transcriptome-directed technologies. The experience with these
      approaches is sufficiently mature to arrive at some generalizable observations.
      First, although expression genomics is a useful approach for the discovery of
      individual candidate genes, its greatest power is in defining class distinctions
      using the collective behavior of gene clusters. Therefore, expression genomic
      output can effectively uncover hierarchies of molecular importance. Second, in
      the hierarchy of factors that determine the expression footprint within a cell,
      cell lineage is the most important, followed by the activity of specific
      biochemical pathways and further followed by the effect of individual genes.
      Lastly, expression profiling is an effective clinical tool that can discern
      prognostic and therapeutic classes. The importance of these gene lists is that
      not only do they describe potential therapeutic targets, but they are effective
      monitors of therapeutic efficacy.

PMID- 15584879
TI  - Application of proteomic technologies to tumor analysis.
AB  - The sequencing of the human genome has had an enormous impact on the proteomic
      analysis of cancer by providing a sequence-based framework for understanding the
      human proteome of tumor cells, tissues, and biological fluids. There is intense
      interest in applying proteomic technologies to uncover, at the protein level,
      processes involved in neoplastic transformation and new biomarkers that correlate
      with early diagnosis, as well as to accelerate the development of new therapeutic
      targets. To that effect, new technologies are being developed in order to meet
      the needs for the high throughput and high sensitivity that is required for
      cancer-related applications of proteomics. These innovative technologies have
      greatly enhanced our ability to separate and characterize complex protein
      mixtures, and have aided our ability to identify proteins with greater
      sensitivity, thereby providing the groundwork for future scientific breakthroughs
      and possibly providing impetus for the development of personalized cancer
      therapy.

PMID- 15584880
TI  - A systematic review of cost-effectiveness analyses of pharmacogenomic
      interventions.
AB  - Cost-effectiveness analysis is a widely used tool to assess the value of
      healthcare interventions. Our objective was to conduct a systematic review of the
      literature on the cost effectiveness of pharmacogenomic interventions. We found
      11 studies that met our inclusion criteria. The most commonly examined disease
      was deep vein thrombosis (n=4), followed by cancer (n=3) and viral infections
      (n=3); the most frequently examined mutation was factor V Leiden (n=5); and the
      majority of the mutations examined were inherited mutations (n=7), although
      several studies looked at acquired (tumor or viral) mutations (n=4). The majority
      of the studies reported a favorable cost-effectiveness ratio for the
      pharmacogenomic-based strategy (n=7), while two studies reported that the
      pharmacogenomic-based strategy was not cost effective and two were equivocal. We
      conclude that there have been few evaluations of the economic costs and benefits
      of pharmacogenomic interventions and they have covered a limited number of
      conditions. Further analyses that can be used to guide the use of
      pharmacogenomics in clinical practice and in developing health policies are
      urgently needed.

PMID- 15584882
TI  - Toward an integrative systems toxicology.

PMID- 15584881
TI  - Homocysteine: exploring its potential as a pharmacodynamic biomarker of
      antifolate chemotherapy.
AB  - For decades it has been well known that elevated levels of homocysteine are
      harmful to humans on the basis of clinical observations derived from classical
      model diseases, such as inherited metabolic disorders. This group of diseases
      includes classical homocystinuria and several other inherited diseases affecting
      the so-called 'transsulfuration pathways'. Homocysteine lies in a metabolic
      checkpoint that interconnects one-carbon-transferring reactions with metabolism
      of sulfur-containing amino acids, since every molecule of 5
      methyltetrahydrofolate derived either from plasma or generated from other folate
      species must be demethylated to liberate the reduced tetrahydrofolate. This
      unidirectional mechanism operates in every cell and has no alternative in
      eukaryotic cells. Antifolates are a group of anticancer agents targeting various
      metabolic steps within folate metabolism. They exert an indirect influence on the
      rate of appearance/disappearance of homocysteine from cellular and plasma
      compartments. Recently, it has been postulated that homocysteine may be a marker
      of the 'pharmacodynamic effect' of methotrexate, but studies attesting to this
      role are only now emerging. Here, we explore the genetic disease of folate and
      homocysteine metabolism and discuss the links between these model disorders with
      pharmacology and pharmacogenetics of folate antagonists used in the clinic. We
      outline possible ways of how homocysteine may be used as a biomarker of
      antifolate therapy.

PMID- 15584883
TI  - Molecular pathology in oncology--the AstraZeneca perspective.
AB  - Growth of the oncology portfolio remains of strategic importance to AstraZeneca,
      and the adoption of new technologies to allow us to enhance this portfolio is
      central to this strategy. With the move away from classical hormonal and
      cytotoxic therapies to the development of more targeted approaches for the
      treatment of cancer, an understanding of the molecular pathology of the disease
      state is becoming vital. Our understanding of the pathogenesis of cancer has
      increased dramatically over the last few decades and with the publication of the
      human genome and the resultant explosion in the field of genetics and genomics,
      AstraZeneca is turning its attention to using these new technologies to enhance
      the oncology R&D platform. In particular, the fields of pharmacogenetics and
      pharmacogenomics in relation to oncology have received much attention and this
      has been mirrored externally both within the pharmaceutical/biotechnology and
      academic sectors. Future products from the AstraZeneca oncology portfolio will
      increasingly rely on the use of genetics and genomics for patient identification
      and stratification, whilst these technologies will also provide a source of novel
      biomarkers and diagnostics that may allow us to streamline the R&D process and
      help us to better understand the biological basis of the diseases we are aiming
      to treat. The AstraZeneca perspective is, however, pragmatic enough to appreciate
      the practical challenges involved in applying pharmacogenetics and genomics not
      only for early drug development, but also in the organization of the healthcare
      infrastructure to undertake timely and complex laboratory investigations.
      Finally, validation of this approach will require carefully controlled clinical
      studies.

PMID- 15584884
TI  - Nuclear receptors: overview and classification.
AB  - The nuclear receptor superfamily comprises a large group of transcription factors
      that play a key regulatory role in development and homeostasis of multicellular
      organisms. A special feature of nuclear receptors is their ability to bind to
      condensed chromatin templates, which makes them important initiators of gene
      transcription. Moreover, the ability of nuclear receptors to sequentially recruit
      a variety of transcription factors and coregulators to target promoters and to
      orchestrate the whole process of gene transcription confirms their biological
      significance and stimulates intensive research and a high level of scientific
      interest in this field. In this review, we summarise current knowledge regarding
      the structure and function of nuclear receptors as principal regulators of gene
      expression. Emphasis is given to the molecular mechanisms of nuclear receptor
      mediated transcriptional activation and repression including recent progress made
      in this area.

PMID- 15584885
TI  - The glucocorticoid receptor as target for classic and novel anti-inflammatory
      therapy.
AB  - Glucocorticoids are well known for their potent anti-inflammatory and immune
      suppressive actions. Their clinical usefulness remains limited due to serious
      side effects that have necessitated a search for ways of improving their benefit
      risk ratios. Mechanistically, glucocorticoids function by interacting with an
      intracellular receptor, the glucocorticoid receptor, a ligand-regulated
      transcription factor that positively or negatively alters the expression of
      specific genes. While it is well accepted that distinct negative regulatory
      action of this receptor forms the basis of the desired anti-inflammatory effects
      of glucocorticoids, not much is known about the function of the receptor that
      contributes to its side effects. The fact that a number of cellular metabolic
      control genes are positively regulated by glucocorticoids makes positive
      regulation of gene expression an attractive mode of action for the adverse
      effects. Positive regulation of gene expression by glucocorticoids, however,
      occurs through different mechanisms and in cell-type specific manner making it
      difficult to predict its possible biological effects in one single assay
      procedure. Recent advances in the molecular action of the receptor are gradually
      revealing different assays and important characteristics that can be put together
      in determining the physiological consequences of the different transactivation
      functions of the glucocorticoid receptor. These will provide invaluable source of
      information for the search of glucocorticoid receptor agonists with potent anti
      inflammatory but reduced side effects.

PMID- 15584886
TI  - PPARs as drug targets to modulate inflammatory responses?
AB  - The three peroxisome proliferator-activated receptors (PPARs) isotypes (PPAR
      alpha, beta/delta and gamma) belong to the nuclear hormone receptor family.
      During the last decade, they have been identified as anti-inflammatory
      transcription factors. Part of this regulation antiinflammatory is mediated
      through negative interference between PPARs and other nuclear factors such as
      NFkB, AP-1 and C/EBP, which regulate innate as well as adaptative immunity. In
      addition, the PPARs control the functions of macrophages, B cells and T cells. In
      this review, we summarise the pathways through which the PPARs control
      inflammatory responses. We also discuss the potential utilisation of PPAR
      specific ligands in the treatment of inflammatory diseases, such as inflammatory
      bowel diseases, atherosclerosis, Parkinson's and Alzheimer's diseases.

PMID- 15584887
TI  - Immunoregulation through 1,25-dihydroxyvitamin D3 and its analogs.
AB  - Beyond its effects on bone metabolism, calcium and phosphorus homeostasis, 1,25
      dihydroxyvitamin D3 (1,25(OH)(2)D(3), calcitriol) exerts profound effects on the
      immune system. We here provide an overview over the metabolism, molecular and
      cellular action of 1,25(OH)(2)D(3) with particular regard to its immunomodulatory
      function. Effects of 1,25(OH)(2)D(3) on the immune system are manyfold and
      include suppression of T cell activation, shaping of cytokine secretion patterns,
      induction of regulatory T cells, modulation of proliferation, and interference
      with apoptosis. 1,25(OH)(2)D(3) further influences maturation, differentiation,
      and migration of antigen presenting cells. Altogether, its immunomodulatory
      potency is comparable to other established immunosuppressants without sharing
      their typical adverse effects. This profile makes 1,25(OH)(2)D(3) a potential
      drug for the treatment of immune-mediated diseases. Yet, the major obstacle for
      its clinical use, its potent calcemic activity, is not overcome to date. The
      identification or generation of novel vitamin D derivatives with dissociated
      calcemic and immunomodulatory properties is therefore a major task. Its success
      might eventually lead to promising drugs for future therapeutic exploitation of a
      wide array of immune diseases, such as psoriasis, multiple sclerosis, rheumatoid
      arthritis, systemic lupus erythematosus, and others.

PMID- 15584888
TI  - Recent advances in the mechanisms of action and physiological functions of the
      retinoid-related orphan receptors (RORs).
AB  - Retinoid-related orphan receptors ROR alpha, -beta, and -gamma are evolutionarily
      related transcription factors belonging to the steroid hormone receptor
      superfamily. Studies of ROR mutant mice revealed that these receptors are
      critical in the regulation of a number of physiological processes. ROR alpha
      plays a key role in the development of the cerebellum particularly in the
      regulation of Purkinje cell differentiation and proliferation of granule cell
      progenitors. ROR alpha has also been implicated in the maintenance of bone tissue
      and mice deficient in ROR alpha exhibit a greater susceptibility to
      atherosclerosis. ROR gamma is essential for lymph node organogenesis and plays a
      key role in the generation or survival of lymphoid tissue inducer (Lti) cells.
      ROR gamma is also critical in thymopoiesis where it controls differentiation and
      promotes the survival of thymocytes by positively regulating Bcl-X(L) expression.
      Several studies have indicated a regulatory role for RORs in circadian behavior.
      In several tissues, the expression of RORs oscillates during circadian rhythm
      while mice deficient in ROR beta exhibit an altered circadian rhythm. ROR alpha
      and ROR gamma have been implicated in the control of various immune responses.
      Mice deficient in ROR gamma exhibit a reduced susceptibility to allergen-induced
      airway inflammation while ROR alpha null mice show a prolonged inflammatory
      response to lipopolysaccharide. Recent analyses of the crystal structure and
      transcriptional activity of RORs revealed that cholesterol and specific
      cholesterol derivatives behave as agonists of ROR alpha while certain retinoids
      function as partial antagonists of ROR beta and ROR gamma. These studies indicate
      that ROR activity and, as a consequence physiological processes regulated by
      RORs, can be modulated by exogenous (ant)agonists. Therefore, the discovery of
      new (ant)agonists may lead to the development of novel therapeutic strategies for
      human disease in which RORs have been implicated.

PMID- 15584889
TI  - Nur77 family of nuclear hormone receptors.
AB  - Among the numerous steroidal and orphan nuclear receptors encoded within
      mammalian genomes, several are involved in the regulation of apoptosis. The
      authors review here recent studies on members of the Nur77 family of orphan
      receptors including Nur77, Nurr1 and Nor-1. These transcription factors were
      initially identified in nerve cells, but also play key roles in the development
      and the effector functions of T lymphocytes and other cells and tissues. Nur77
      can also act as a modulator of transcription for other orphan steroid receptors.
      Regulation of the Nur77 orphan receptor family members are tightly associated
      with transcriptional co-factors including co-repressors and co-activators. Also,
      one interesting aspect of the Nur77 orphan receptor family members is that
      depending on its location in the mitochondria or nucleus, these orphan receptors
      exhibit differential roles in determining cell death or cell growth. Numerous
      studies demonstrated the importance of Nur77 subfamily members in regulations of
      early embryogenesis, thymocyte negative selection, gene expression in
      hypothalamic-pituitary adrenal axis, chronic inflammatory response, and vascular
      smooth muscle cell proliferation. This review intends to integrate the importance
      of nuclear receptors in health and disease, and as potential targets for drug
      discovery by comparing the difference and similarity in the biochemical
      mechanisms of action used by the classic steroid/endocrine receptors and the
      orphan receptors to lead to identification of novel targets in manipulating the
      transcriptional functions and physiologic pathways for the orphan nuclear
      receptors.

PMID- 15584890
TI  - Interactions of sex steroids with mechanisms of inflammation.
AB  - Differential sex-specific liability to inflammatory and autoimmune diseases, and
      changes in symptom severity in association with physiological fluctuations in
      gonadal secretions are indicative of significant contribution of sex hormones to
      the regulation of immune responsiveness. Apart from a postulated role in sex
      specific organization of the immune system during ontogeny, gonadal steroids may
      influence the immune response in numerous ways. This review analyzes existing
      concepts, experimental and clinical data, aiming at the definition of cellular
      and molecular mechanisms which may serve as suitable targets for discovery of
      immunomodulatory drugs whose principal feature is specific interaction with sex
      hormone receptors. Separation of immunomodulatory effects of sex steroids from
      those which are exerted by glucocorticoids, and subsequent identification of sex
      hormone-specific molecular targets appear to be crucial for the justification of
      drug discovery on the basis of sex steroid receptor ligands.

PMID- 15584891
TI  - Pulmonary involvement in inflammatory bowel disease.
AB  - Inflammatory bowel disease is a systemic illness that may involve the lung. The
      most frequent manifestation is bronchial inflammation and suppuration with or
      without bronchiectasis. Bronchoalveolar lavage data show an increase percentage
      of neutrophils and steroids are very effective in the majority of cases. Some
      patients present severe tracheal inflammation and obstruction with an
      inflammatory mass bulging into the tracheal lumen. Others show a small airway
      involvement with or without bronchiolitis obliterans organizing pneumonia pattern
      and have an equivocal response to steroids. In recent years many investigators
      demonstrated latent pulmonary involvement with a reduction in lung transfer
      factor and a small airways disorders.

PMID- 15584892
TI  - Pleural involvement in systemic disorders.
AB  - The collagen vascular diseases are a heterogeneous group of immunologically
      mediated inflammatory disorders. Frequently, these diseases affect organ systems
      outside the thorax as their primary manifestation, but may involve the pleura as
      a single presenting feature, as part of multisystem involvement, or as an
      isolated manifestation of a disease that is otherwise quiescent. In this article,
      we review the manifestations of respiratory disease caused by rheumatoid
      arthritis, systemic lupus erythematosus, scleroderma,
      polymyositis/dermatomyositis, mixed connective tissue disease, Sjogren's
      syndrome, Wegener's granulomatosis, and sarcoidosis.

PMID- 15584893
TI  - The lung in immune-mediated disorder: rheumatoid arthritis.
AB  - Various pleuro-pulmonary abnormalities are known to complicate vascular collagen
      diseases, particularly, rheumatoid arthritis. Each component of the respiratory
      system is affected, either separately or in combination. Although most pulmonary
      complications appear in an established case of collagen vascular disease, in
      certain conditions, the lung disease precedes the more typical manifestation.
      While some complications are asymptomatic and tend to be resolved spontaneously
      (for e.g. pleuritis and rheumatoid nodules), others may cause severe or fatal
      conditions (interstitial pneumonia and constrictive bronchiolitis). The incidence
      of interstitial lung disease is increasing in vascular collagen disease. This may
      be mainly attributed to the increase use of invasive techniques such as
      bronchoscopy and video-assisted thoracoscopic surgery and in part due to the use
      of high resolution computed tomography, and functional pulmonary tests.

PMID- 15584894
TI  - Pulmonary complications in diabetes mellitus: the role of glycemic control.
AB  - Insulin deficiency induces an increase in blood glucose levels that, in long run,
      becomes toxic for many organs and systems. Microangiopathy and derangements in
      the immune function are known consequences of hyperglycemia, but the way in which
      these systemic alterations may affect pulmonary function has been scarcely
      investigated. Although confirmation from large clinical trials is still to come,
      the diabetic disease seems to hit the pulmonary microcirculation as any other
      organ by increasing vessel wall thickness and impairing gas exchange, which leads
      to a measurable loss of function and respiratory efficiency. In addition, a
      diabetic lung is more susceptible to low respiratory tract infections by atypical
      microorganisms and more likely to host severe episodes of pneumonia than a
      normal, non-diabetic lung. This is a review of current knowledge on the impact of
      diabetes mellitus in lung health. We have paid special attention to the role of
      metabolic control in preventing damage to the lung by sustained hyperglycemia.

PMID- 15584895
TI  - Pulmonary hypertension and systemic diseases.
AB  - Secondary pulmonary hypertension (sPH) may develop as a result of few systemic
      diseases as endocrine diseases, HIV infection, collagen diseases, liver and
      hematological disorders. In this review we discuss the role of systemic diseases
      in inducing PH starting from a pathological classification.

PMID- 15584896
TI  - Primary lung lymphoma.
AB  - Lymphoproliferative disorders affecting the lung are infrequent. Therefore the
      diagnosis is often not easy, specially when the lung is primary affected.
      Moreover, new clinical-pathological entities are responsible of primary lung
      lymphoma that require specific treatment. It is important to keep in mind the
      chance that lung may be involved by lymphoproliferative disorders so to avoid the
      mistake of the misdiagnosis of this curable diseases since sometimes they have a
      good prognosis and a very different management from epithelial neoplasia of the
      lung.

PMID- 15584897
TI  - Interaction of three-finger toxins with phospholipid membranes: comparison of S-
      and P-type cytotoxins.
AB  - The CTs (cytotoxins) I and II are positively charged three-finger folded proteins
      from venom of Naja oxiana (the Central Asian cobra). They belong to S- and P-type
      respectively based on Ser-28 and Pro-30 residues within a putative phospholipid
      bilayer binding site. Previously, we investigated the interaction of CTII with
      multilamellar liposomes of dipalmitoylphosphatidylglycerol by wide-line (31)P-NMR
      spectroscopy. To compare interactions of these proteins with phospholipids, we
      investigated the interaction of CTI with the multilamellar liposomes of
      dipalmitoylphosphatidylglycerol analogously. The effect of CTI on the chemical
      shielding anisotropy and deformation of the liposomes in the magnetic field was
      determined at different temperatures and lipid/protein ratios. It was found that
      both the proteins do not affect lipid organization in the gel state. In the
      liquid crystalline state of the bilayer they disturb lipid packing. To get
      insight into the interactions of the toxins with membranes, Monte Carlo
      simulations of CTI and CTII in the presence of the bilayer membrane were
      performed. It was found that both the toxins penetrate into the bilayer with the
      tips of all the three loops. However, the free-energy gain on membrane insertion
      of CTI is smaller (by approximately 7 kcal/mol; 1 kcal identical with 4.184 kJ)
      when compared with CTII, because of the lower hydrophobicity of the membrane
      binding site of CTI. These results clearly demonstrate that the P-type cytotoxins
      interact with membranes stronger than those of the S-type, although the mode of
      the membrane insertion is similar for both the types.

PMID- 15584898
TI  - Sprouty-4 negatively regulates cell spreading by inhibiting the kinase activity
      of testicular protein kinase.
AB  - TESK1 (testicular protein kinase 1) is a serine/threonine kinase that
      phosphorylates cofilin and plays a critical role in integrin-mediated actin
      cytoskeletal reorganization and cell spreading. We previously showed that TESK1
      interacts with Sprouty-4 (referred to as Spry4), an inhibitor of growth factor
      induced Ras/MAP (mitogen-activated protein) kinase signalling, but the functional
      role of this interaction has remained unknown. In the present study, we show that
      Spry4 inhibits the kinase activity of TESK1 by binding to it through the C
      terminal cysteine-rich region. Expression of Spry4 in cultured cells suppressed
      integrin-mediated cell spreading, and TESK1 reversed the inhibitory effect of
      Spry4 on cell spreading. Furthermore, Spry4 suppressed integrin- and TESK1
      mediated cofilin phosphorylation during the spreading of cells on laminin. These
      findings suggest that Spry4 suppresses cell spreading by inhibiting the kinase
      activity of TESK1. Although tyrosine phosphorylation is required for the
      inhibitory activity of Spry4 on a Ras/MAP kinase pathway, mutation of the
      corresponding tyrosine residue (Tyr-75 in human Spry4) to an alanine had no
      apparent effect on its inhibitory actions on TESK1 activity and cell spreading,
      which suggests a novel cellular function of Spry to regulate the actin
      cytoskeleton, independent of its inhibitory activity on the Ras/MAP kinase
      signalling.

PMID- 15584899
TI  - Aha1 competes with Hop, p50 and p23 for binding to the molecular chaperone Hsp90
      and contributes to kinase and hormone receptor activation.
AB  - The ATP-dependent molecular chaperone Hsp90 (heat-shock protein 90) is essential
      for the maturation of hormone receptors and protein kinases. During the process
      of client protein activation, Hsp90 co-operates with cofactors/co-chaperones of
      unique sequence, e.g. Aha1 (activator of Hsp90 ATPase 1), p23 or p50, and with
      cofactors containing TPR (tetratricopeptide repeat) domains, e.g. Hop,
      immunophilins or cyclophilins. Although the binding sites for these different
      types of cofactors are distributed along the three domains of Hsp90, sterical
      overlap and competition for binding sites restrict the combinations of cofactors
      that can bind to Hsp90 at the same time. The recently discovered cofactor Aha1
      associates with the middle domain of Hsp90, but its relationship to other
      cofactors of the molecular chaperone is poorly understood. Therefore we analysed
      whether complexes of Aha1, p23, p50, Hop and a cyclophilin with Hsp90 are
      disrupted by the other four cofactors by gel permeation chromatography using
      purified proteins. It turned out that Aha1 competes with the early cofactors Hop
      and p50, but can bind to Hsp90 in the presence of cyclophilins, suggesting that
      Aha1 acts as a late cofactor of Hsp90. In contrast with p50, which can bind to
      Hop, Aha1 does not interact directly with any of the other four cofactors. In
      vivo studies in yeast and in mammalian cells revealed that Aha1 is not specific
      for kinase activation, but also contributes to maturation of hormone receptors,
      proposing a general role for this cofactor in the activation of Hsp90-dependent
      client proteins.

PMID- 15584900
TI  - GFP-PCNA as an S-phase marker in embryos during the first and subsequent cell
      cycles.
AB  - BACKGROUND INFORMATION: Proliferating cell nuclear antigen (PCNA) is a key
      component of the DNA replication machinery involved in the process of DNA
      elongation, recombination, methylation and repair. We have used PCNA fused with
      green fluorescent protein (GFP-PCNA) as a convenient tool to show the progress of
      S-phase in single embryos in vivo. Here we make a comparison between Hoechst
      33342 and GFP-PCNA as in vivo event markers for DNA synthesis. Hoechst 33342 and
      DAPI (4,6-diamidino-2-phenylindole) have been used as a simple and rapid method
      for assessing membrane permeability and staining DNA in mammalian cells. However,
      it is difficult to use these dyes in living embryos during cell cycle progression
      studies over long periods of time as they are phototoxic. Moreover, though
      Hoechst staining reveals nuclear morphology, it gives no information about the
      progress of S-phase. RESULTS: We have microinjected or expressed a GFP-PCNA
      chimera to develop a method which enables visualization of S-phase in sea urchin
      and Caenorhabditis elegans embryos during the first and subsequent embryonic cell
      cycles and in Drosophila stage 4 embryos during syncytial nuclear divisions. We
      find that nuclear accumulation of GFP-PCNA correlates with S-phase onset. Loss of
      the chimera from the nucleus occurs when the nuclear envelope breaks down at
      mitosis. CONCLUSIONS: GFP-PCNA is a accurate and non-toxic marker of S-phase in
      embryos during early development.

PMID- 15584901
TI  - Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders.
AB  - DP (dipeptidyl peptidase) IV is the archetypal member of its six-member gene
      family. Four members of this family, DPIV, FAP (fibroblast activation protein),
      DP8 and DP9, have a rare substrate specificity, hydrolysis of a prolyl bond two
      residues from the N-terminus. The ubiquitous DPIV glycoprotein has proved
      interesting in the fields of immunology, endocrinology, haematology and
      endothelial cell and cancer biology and DPIV has become a novel target for Type
      II diabetes therapy. The crystal structure shows that the soluble form of DPIV
      comprises two domains, an alpha/beta-hydrolase domain and an eight-blade beta
      propeller domain. The propeller domain contains the ADA (adenosine deaminase)
      binding site, a dimerization site, antibody epitopes and two openings for
      substrate access to the internal active site. FAP is structurally very similar to
      DPIV, but FAP protein expression is largely confined to diseased and damaged
      tissue, notably the tissue remodelling interface in chronically injured liver.
      DPIV has a variety of peptide substrates, the best studied being GLP-1 (glucagon
      like peptide-1), NPY (neuropeptide Y) and CXCL12. The DPIV family has roles in
      bone marrow mobilization. The functional interactions of DPIV and FAP with
      extracellular matrix confer roles for these proteins in cancer biology. DP8 and
      DP9 are widely distributed and indirectly implicated in immune function. The DPL
      (DP-like) glycoproteins that lack peptidase activity, DPL1 and DPL2, are brain
      expressed potassium channel modulators. Thus the six members of the DPIV gene
      family exhibit diverse biological roles.

PMID- 15584902
TI  - Biochemical and kinetic characterization of BACE1: investigation into the
      putative species-specificity for beta- and beta'-cleavage sites by human and
      murine BACE1.
AB  - Beta-amyloid peptides (Abeta) are produced by a sequential cleavage of amyloid
      precursor protein (APP) by beta- and gamma-secretases. The lack of Abeta
      production in beta-APP cleaving enzyme (BACE1)(-/-) mice suggests that BACE1 is
      the principal beta-secretase in mammalian neurons. Transfection of human APP and
      BACE1 into neurons derived from wild-type and BACE1(-/-) mice supports cleavage
      of APP at the canonical beta-secretase site. However, these studies also revealed
      an alternative BACE1 cleavage site in APP, designated as beta', resulting in
      Abeta peptides starting at Glu11. The apparent inability of human BACE1 to make
      this beta'-cleavage in murine APP, and vice versa, led to the hypothesis that
      this alternative cleavage was species-specific. In contrast, the results from
      human BACE1 transgenic mice demonstrated that the human BACE1 is able to cleave
      the endogenous murine APP at the beta'-cleavage site. To address this
      discrepancy, we designed fluorescent resonance energy transfer peptide substrates
      containing the beta- and beta'-cleavage sites within human and murine APP to
      compare: (i) the enzymatic efficiency; (ii) binding kinetics of a BACE1 active
      site inhibitor LY2039911; and (iii) the pharmacological profiles for human and
      murine recombinant BACE1. Both BACE1 orthologs were able to cleave APP at the
      beta- and beta'-sites, although with different efficiencies. Moreover, the
      inhibitory potency of LY2039911 toward recombinant human and native BACE1 from
      mouse or guinea pig was indistinguishable. In summary, we have demonstrated, for
      the first time, that recombinant BACE1 can recognize and cleave APP peptide
      substrates at the postulated beta'-cleavage site. It does not appear to be a
      significant species specificity to this cleavage.

PMID- 15584903
TI  - Intracellularly generated amyloid-beta peptide counteracts the antiapoptotic
      function of its precursor protein and primes proapoptotic pathways for activation
      by other insults in neuroblastoma cells.
AB  - Most mutations in amyloid precursor proteins (APPs) linked to early onset
      familial Alzheimer's disease (FAD) increase the production of amyloid-beta
      peptides ending at residue 42 (Abeta42), which are released from APP by beta- and
      gamma-secretase cleavage. Stably transfected cells expressing wild-type human APP
      (APP(WT)) were more resistant to apoptosis-inducing treatments than cells
      expressing FAD-mutant human APP (APP(FAD)). Preventing Abeta42 production with an
      M596I mutation (beta-), which blocks beta-secretase cleavage of APP, or by
      treatment with a gamma-secretase inhibitor increased the resistance of APP(FAD)
      expressing cells to apoptosis. Exposing hAPP(FAD/beta-) cells to exogenous
      Abeta42 or conditioned medium from Abeta42-producing APP(FAD) cells did not
      diminish their resistance to apoptosis. Preventing APP from entering the distal
      secretory pathway, where most Abeta peptides are generated, by retaining APP in
      the endoplasmic reticulum (ER)/intermediate compartment (IC) increased the
      resistance of APP(FAD)-expressing cells to apoptosis and did not alter the
      resistance of APP(WT)-expressing cells. p53-mediated gene transactivation after
      apoptosis-inducing treatments was much stronger in APP(FAD) cells than in
      hAPP(WT) or hAPP(FAD/beta-) cells. In contrast, upon induction of ER stress,
      cells expressing APP(FAD), hAPP(FAD/beta-), or APP(WT) had comparable levels of
      glucose-regulated protein-78 mRNA, an unfolded protein response indicator. We
      conclude that Abeta, especially intracellular Abeta, counteracts the
      antiapoptotic function of its precursor protein and predisposes cells to p53
      mediated, and possibly other, proapoptotic pathways.

PMID- 15584904
TI  - BCL-2-induced glioma cell invasiveness depends on furin-like proteases.
AB  - Migration and invasion are prerequisites for the neoplastic phenotype of
      malignant glioma. Ectopic expression of BCL-2 enhances migration and invasion of
      glioma cells and promotes their synthesis of transforming growth factor-beta2
      (TGF-beta2). We here report that BCL-2-expressing cells show enhanced expression
      and activity of the proprotein convertase, furin, which processes
      metalloproteinases (MMP) and TGF-beta. Consistent with a biological role for a
      BCL-2-dependent increase in furin-like protease (FLP) activity, BCL-2-expressing
      cells exhibit enhanced MMP activity. Both a pseudosubstrate furin inhibitor,
      decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk), or alpha 1-anti
      trypsin Portland (PDX), a recombinant furin-inhibitory protein, suppress
      constitutive and BCL-2-mediated MMP activity and invasion. This inhibition is not
      overcome by TGF-beta or hepatocyte growth factor (HGF). A neutralizing TGF-beta
      antibody attenuates, but not abrogates, the invasive properties conferred by
      exogenous expression of BCL-2, whereas the MMP inhibitor o-phenantroline (o-PA)
      abolishes the pro-invasive action of BCL-2. Exogenous HGF results in enhanced,
      and expression of dominant-negative ezrin in reduced, FLP activity, and dec-RVKR
      cmk blunts the HGF-induced expression of mature TGF-beta2. Consequently, HGF and
      BCL-2 family proteins use a furin-dependent pathway to promote invasion via TGF
      beta and MMP in human malignant glioma cells and the pro-invasive properties of
      TGF-beta require furin- dependent MMP activity.

PMID- 15584905
TI  - S100B protein is released by in vitro trauma and reduces delayed neuronal injury.
AB  - S100B protein in brain is produced primarily by astrocytes, has been used as a
      marker for brain injury and has also been shown to be neurotrophic and
      neuroprotective. Using a well characterized in vitro model of brain cell trauma,
      we examined the potential role of exogenous S100B in preventing delayed neuronal
      injury. Neuronal plus glial cultures were grown on a deformable Silastic membrane
      and then subjected to strain (stretch) injury produced by a 50 ms displacement of
      the membrane. We have previously shown that this injury causes an immediate, but
      transient, nuclear uptake of the fluorescent dye propidium iodide by astrocytes
      and a 24-48 h delayed uptake by neurons. Strain injury caused immediate release
      of S100-beta with further release by 24 and 48 h. Adding 10 or 100 nm S100B to
      injured cultures at 15 s, 6 h or 24 h after injury reduced delayed neuronal
      injury measured at 48 h. Exogenous S100B was present in the cultures through 48
      h. These studies directly demonstrate the release and neuroprotective role of
      S100B after traumatic injury and that, unlike most receptor antagonists used for
      the treatment of trauma, S100B is neuroprotective when given at later, more
      therapeutically relevant time points.

PMID- 15584906
TI  - Dopamine D3 receptor stimulation promotes the proliferation of cells derived from
      the post-natal subventricular zone.
AB  - In the adult mammalian brain, neural stem cells persist in the subventricular
      zone (SVZ) where dopamine D3 receptors are expressed. Here, we demonstrate that
      addition of 1 microm apomorphine increases cell numbers in post-natal SVZ cell
      cultures. This effect was prevented by a co-treatment with haloperidol, sulpiride
      or U-99194A, a D3-preferring antagonist, and mimicked by the dopamine D3 receptor
      selective agonist 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). EC50 values were
      4.04 +/- 1.54 nm for apomorphine and 0.63 +/- 0.13 nm for 7-OH-DPAT, which fits
      the pharmacological profile of the D3 receptor. D3 receptors were detected in SVZ
      cells by RT-PCR and immunocytochemistry. D3 receptors were expressed in numerous
      beta-III tubulin immunopositive cells. The fraction of apoptotic nuclei remained
      unchanged following apomorphine treatment, thus ruling out any possible effect on
      cell survival. In contrast, proliferation was increased as both the proportion of
      nuclei incorporating bromo-deoxyuridine and the expression of the cell division
      marker cyclin D1 were enhanced. These findings provide support for a regulatory
      role of dopamine over cellular dynamics in post-natal SVZ.

PMID- 15584907
TI  - The neuregulin receptor, ErbB4, is not required for normal development and adult
      maintenance of the substantia nigra pars compacta.
AB  - Degeneration of dopaminergic neurons in the substantia nigra is associated with
      one of the most prominent human neurological disorders, Parkinson's disease. It
      is therefore of high interest to identify molecules with trophic effects on this
      neuronal population. We show here that the neuregulin receptor ErbB4 is
      differentially expressed in mesencephalic dopaminergic neurons, found in the
      substantia nigra and in a subregion of the ventral tegmentum but not in the
      retrorubral field. Early developmental onset and continued expression of ErbB4
      into the adult and the presence of two high affinity ligands, neuregulin-1 and
      betacellulin, in the basal ganglia, suggested that these molecules might
      participate in the differentiation and/or maintenance of the nigrostriatal
      system. In order to address this hypothesis, we used a loxP flanked ErbB4 allele
      in combination with a nestin-Cre transgene and generated brain-specific ErbB4
      null mice. These mutant animals survived into adulthood. The distribution of
      dopaminergic cell bodies in the midbrain, the expression of numerous genes
      specific to mesencephalic dopaminergic neurons, and the axonal projection to the
      basal ganglia all appeared normal. Finally, an assessment of their motor function
      revealed no behavioral deficits. The apparent lack of any mutant phenotype
      suggests the presence of a strong compensatory mechanism.

PMID- 15584908
TI  - Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor
      protein carboxy terminal fragment-associated cytotoxicity.
AB  - Inheritance of the apolipoprotein (APO) E gene epsilon4 or epsilon2 allele alters
      the risk of developing Alzheimer disease (AD), while increased alpha-tocopherol
      (AT) intake appears to lower the risk of AD. As APOE is a major apolipoprotein in
      the CNS and AT in vivo is transported in lipoproteins, we tested the hypothesis
      that CNS lipoproteins, as modeled by relevant concentrations of high density
      lipoprotein (HDL), and AT would interact to suppress neurotoxicity in a cell
      culture model of amyloid beta (Abeta)- related toxicity. These cells
      conditionally express C99-derived peptides, proposed to be a key step in AD
      pathogenesis; this expression is closely associated with subsequent cell death.
      We found that physiologic concentrations of lipoproteins present in the CNS
      protected from C99-associated toxicity and provided evidence for two mechanisms
      of protection. The first was AT-independent, APOE isoform-dependent, and most
      potent for the APOE2 isoform. The second was a synergistic protection afforded by
      a combination of APOAI, or less so APOE, and AT. These data provide a novel
      explanation for the apparent AD-protective effect of inheriting an epsilon2 APOE
      allele, and suggest that optimizing AT enrichment of CNS lipoproteins or devising
      APOAI mimetics may augment AT efficacy in treating AD.

PMID- 15584909
TI  - Early calpain-mediated proteolysis following AMPA receptor activation compromises
      neuronal survival in cultured hippocampal neurons.
AB  - In this work, we investigated the involvement of calpains in the neurotoxicity
      induced by short-term exposure to kainate (KA) in non-desensitizing conditions of
      AMPA receptor activation (cyclothiazide present, CTZ), in cultured rat
      hippocampal neurons. The calpain inhibitor MDL28170 had a protective effect in
      cultures treated with KA plus CTZ (p < 0.01), preventing the decrease in MTT
      reduction caused by exposure to KA (p < 0.001). Caspase inhibition by ZVAD-fmk
      was not neuroprotective against the toxic effect of KA. At 1 h after treatment,
      we could already observe significantly increased calpain activity, which was
      prevented by MDL 28170 and NBQX. Western blot analysis of calpain substrates,
      GluR1, neuronal nitric oxide synthase (nNOS) and nonerythroid spectrin (fodrin),
      showed a time-dependent and MDL 28170-sensitive proteolysis of these proteins.
      This effect was due to calpains, but not caspases, since ZVAD-fmk was ineffective
      in preventing proteolytic events. Breakdown products of fodrin (BDPs) were
      detected as early as 15 min after exposure to KA. Overall, these results show
      early activation of calpains following activation of AMPA receptors as well as
      compromise of neuronal survival, likely due to proteolytic events that affect
      proteins involved in neuronal signaling.

PMID- 15584911
TI  - Phosphorylation of proteins involved in activity-dependent forms of synaptic
      plasticity is altered in hippocampal slices maintained in vitro.
AB  - The acute hippocampal slice preparation has been widely used to study the
      cellular mechanisms underlying activity-dependent forms of synaptic plasticity
      such as long-term potentiation (LTP) and long-term depression (LTD). Although
      protein phosphorylation has a key role in LTP and LTD, little is known about how
      protein phosphorylation might be altered in hippocampal slices maintained in
      vitro. To begin to address this issue, we examined the effects of slicing and in
      vitro maintenance on phosphorylation of six proteins involved in LTP and/or LTD.
      We found that AMPA receptor (AMPAR) glutamate receptor 1 (GluR1) subunits are
      persistently dephosphorylated in slices maintained in vitro for up to 8 h. alpha
      calcium/calmodulin-dependent kinase II (alphaCamKII) was also strongly
      dephosphorylated during the first 3 h in vitro but thereafter recovered to near
      control levels. In contrast, phosphorylation of the extracellular signal
      regulated kinase ERK2, the ERK kinase MEK, proline-rich tyrosine kinase 2 (Pyk2),
      and Src family kinases was significantly, but transiently, increased.
      Electrophysiological experiments revealed that the induction of LTD by low
      frequency synaptic stimulation was sensitive to time in vitro. These findings
      indicate that phosphorylation of proteins involved in N-methyl-D-aspartate (NMDA)
      receptor-dependent forms of synaptic plasticity is altered in hippocampal slices
      and suggest that some of these changes can significantly influence the induction
      of LTD.

PMID- 15584910
TI  - Expression profiling upon Nex1/MATH-2-mediated neuritogenesis in PC12 cells and
      its implication in regeneration.
AB  - The expression of Nex1 peaks during brain development when neurite outgrowth and
      synaptogenesis are highly active. We previously showed that Nex1 is a critical
      effector of the nerve growth factor (NGF) pathway and its overexpression results
      in spontaneous neuritogenesis. Furthermore, the PC12-Nex1 cells exhibit
      accelerated neurite extension upon NGF exposure, and have the capacity to
      regenerate neurites in the absence of NGF. In this study, we identify the
      repertoire of genes targeted by Nex1 to unravel the molecular mechanisms by which
      Nex1 promotes differentiation and regeneration. Our transcriptional analysis
      reveals that Nex1 modulates a wide spectrum of genes with diverse functions, many
      of them being key downstream regulators of the NGF pathway, and critical to
      neuritogenesis, such as microtubules, microtubule-associated proteins (MAPs) and
      intermediate filaments. We also provide the first evidence that a basic helix
      loop-helix (bHLH) protein stimulates the expression of the cyclin-dependent
      kinase (CDK) inhibitors belonging to the INK4 family, which plays a role in
      promoting cell-cycle arrest. Finally, we show a dramatic synergistic effect
      between Nex1 and cAMP, resulting in an impressive regeneration of an elaborate
      and dense neurite network. Thus, Nex1 has endowed the PC12-Nex1 cells with a
      distinct combination of gene products that takes part in the complex regulation
      of neuritogenesis and regeneration.

PMID- 15584912
TI  - Neurotrophic and neuroprotective effects of the neuregulin glial growth factor-2
      on dopaminergic neurons in rat primary midbrain cultures.
AB  - Glial growth factor-2 (GGF2) and other neuregulin (NRG) isoforms have been shown
      to play important roles in survival, migration, and differentiation of certain
      neural and non-neural cells. Because midbrain dopamine (DA) cells express the NRG
      receptor, ErbB4, the present study examined the potential neurotrophic and/or
      neuroprotective effects of GGF2 on cultured primary dopaminergic neurons.
      Embryonic day 14 rat mesencephalic cell cultures were maintained in serum-free
      medium and treated with GGF2 or vehicle. The number of tyrosine hydroxylase
      positive (TH+) neurons and high-affinity [3H]DA uptake were assessed at day in
      vitro (DIV) 9. Separate midbrain cultures were treated with 100 ng/mL GGF2 on DIV
      0 and exposed to the catecholamine-specific neurotoxin 6-hydroxydopamine (6-OHDA)
      on DIV 4. GGF2 treatment significantly increased DA uptake, the number of TH+
      neurons, and neurite outgrowth when compared to the controls in both the serum
      free and the 6-OHDA-challenged cultures. Furthermore, three NRG receptors were
      detected in the midbrain cultures by western blot analysis. Immunostaining for
      glial fibrillary acidic protein revealed that GGF2 also weakly promoted
      mesencephalic glial proliferation in the midbrain cultures. These results
      indicate that GGF2 is neurotrophic and neuroprotective for developing
      dopaminergic neurons and suggest a role for NRGs in repair of the damaged
      nigrostriatal system that occurs in Parkinson's disease.

PMID- 15584913
TI  - Developmental regulation of tissue transglutaminase in the mouse forebrain.
AB  - Tissue transglutaminase (tTG) is a multifunctional enzyme that catalyzes both
      transamidation and GTPase reactions. In cell culture models tTG-mediated
      transamidation positively regulates many processes that occur in vivo during the
      mammalian brain growth spurt (BGS), including neuronal differentiation, neurite
      outgrowth, synaptogenesis and cell death mechanisms. However, little is known
      about the levels of tTG expression and transglutaminase (TG) activity during
      mammalian brain development. In this study, C57BL/6 mouse forebrains were
      collected at embryonic day (E) 12, E14, E17, postnatal day (P) 0, P7 and P56 and
      analyzed for tTG expression and TG activity. RT-PCR analysis demonstrated that
      tTG mRNA content increases during mouse forebrain development, whereas immunoblot
      analysis demonstrated that tTG protein content decreases during this time. TG
      activity was low in prenatal mouse forebrain but increased fivefold to peak at
      P0, which corresponds with the beginning of the mouse BGS. Further analysis
      demonstrated that the lack of temporal correlation between tTG protein content
      and TG activity is the result of an endogenous inhibitor of tTG that is present
      in prenatal but not postnatal mouse forebrain. These results demonstrate for the
      first time that tTG enzymatic activity in the mammalian forebrain is
      developmentally regulated by post-translational mechanisms.

PMID- 15584914
TI  - The response of synaptophysin and microtubule-associated protein 1 to restraint
      stress in rat hippocampus and its modulation by venlafaxine.
AB  - As part of our continuing study of neural plasticity in rat hippocampus, we
      examined two structural proteins involved in neuronal plasticity, synaptophysin
      (SYP) and microtubule-associated protein 1 (MAP1) for their response to repeated
      restraint stress and modulation of such response by the antidepressant drug
      venlafaxine. This drug has the pharmacological action of inhibiting the reuptake
      of serotonin and norepinephrine in nerve terminals. We subjected the rats to
      restraint stress for 4 h per day for three days, and then injected the animals
      intraperitoneally (i.p.) with vehicle or 5 mg/kg/day of venlafaxine for various
      time periods. In all, eight groups of 10 rats each were used. The expression of
      these two proteins in hippocampal tissue of the rats was examined by means of
      western blot and immunohistochemical staining techniques. We found that restraint
      stress decreased the expression of SYP in the rat hippocampus by 50% (p < 0.01),
      and increased the expression of MAP1 by 60% (p < 0.01). SYP returned to the pre
      stress levels in three weeks and MAP1 in two weeks. In animals treated with
      venlafaxine post-stress, SYP returned to pre-stress levels after 2 weeks and MAP1
      after 1 week. These findings enhance our understanding of the compromise of the
      hippocampus by stressful assaults, and may be relevant to the action of
      venlafaxine in the treatment of patients with major depression, a mental disease
      thought to be related to the mal-adaptation of subjects to environmental
      stressors.

PMID- 15584915
TI  - Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are
      decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory
      induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2.
AB  - We previously demonstrated that brain cyclooxygenase (COX)-2 mRNA and protein
      levels, and prostaglandin E2 (PGE2) level, are down-regulated in cytosolic
      phospholipase A2 (cPLA2) -deficient mice. To further investigate the interaction
      between upstream and downstream enzymes involved in brain prostaglandin
      synthesis, we examined expression and activity of COX-1, of different PLA2
      enzymes and of prostaglandin E synthase (PGES) enzymes in COX-2(-/-) mice. We
      found that the PGE2 level was decreased by 51.5% in the COX-2(-/-) mice brains,
      indicating a significant role of COX-2 in brain formation of PGE2. However, when
      we supplied exogenous arachidonic acid (AA) to brain homogenates, COX activity
      was increased in the COX-2(-/-) mice, suggesting a compensatory activation of COX
      1 and an intracellular compartmentalization of the COX isozymes. Consistent with
      COX-1 increased activity, brain expression of COX-1 protein and mRNA also was
      increased. Activity and expression of cPLA2 and secretory PLA2 (sPLA2) enzymes,
      supplying AA to COX, were significantly increased. Also, the PGE2 biosynthetic
      pathway downstream from COX-2 was affected in the COX-2(-/-) mice, as decreased
      expression of microsomal prostaglandin E synthase-2 (mPGES-2), but not mPGES-1 or
      cytosolic PGES, was observed. Overall, the data suggest that compensatory
      mechanisms exist in COX-2(-/-) mice and that mPGES-2 is functionally coupled with
      COX-2.

PMID- 15584916
TI  - Interaction of human and mouse Abeta peptides.
AB  - Transgenic mice over-expressing mutant human amyloid precursor protein have
      become an important tool for research on Alzheimer's disease (AD) and, in
      particular, for therapeutic screening. Many models have reported formation of
      amyloid plaques with age as is detected in AD. However, the plaques generated in
      transgenic mice are more soluble than human plaques. Differences in solubility
      may occur for a number of reasons; one proposal is the presence of murine Abeta
      peptides within the CNS milieu. Here, we report the interaction of human and
      murine Abeta peptides, Abeta40 and Abeta42, utilizing a fluorescence assay to
      monitor formation of mixed pre-fibrillar aggregates, electron microscopy to
      examine morphological characteristics and detergent solubility to monitor
      stability. Our results demonstrate that interspecies Abeta aggregates and fibres
      are readily formed and are more stable than homogenous human fibres. Furthermore,
      these results suggest that the presence of endogenous murine Abeta in human APP
      transgenic mice does not account for the increased solubility of plaques.

PMID- 15584917
TI  - Arrestin2 expression selectively increases during neural differentiation.
AB  - Arrestins and G protein-coupled receptor kinases (GRKs) are key players in
      homologous desensitization of G protein-coupled receptors. Two non-visual
      arrestins, arrestin2 and 3, and five GRKs (GRK2, 3, 4, 5 and 6) are involved in
      desensitization of many receptors. Here, we demonstrate a steady increase in
      arrestin2 expression during prenatal development. The density of arrestin2 mRNA
      is higher in differentiated areas as compared with proliferative zones, whereas
      arrestin3 mRNA shows the opposite distribution. At embryonic day 14,
      concentrations of arrestin proteins are similar (32-34 nM). Later in development,
      arrestin2 expression rises, leading to a fourfold excess of arrestin2 over
      arrestin3 at birth (48 vs. 11 ng/mg protein or 102 vs. 25 nM). Among GRKs, only
      GRK5 increased with embryonic age from 124 nm at E14 to 359 nM at birth.
      Similarly, in vitro differentiation of cultured precursor cells, neurospheres,
      leads to a significant up-regulation of arrestin2 resulting in > 20-fold excess
      of arrestin2 (160 vs. 7 nM). GRK5 is the only subtype increased with neurosphere
      differentiation, although the change is only about twofold. The data demonstrate
      selective increases in the expression of arrestin2 associated with neural
      development and suggest specific yet unappreciated roles for arrestin2 in neural
      differentiation.

PMID- 15584918
TI  - Calcitonin gene-related peptide regulates gene transcription in primary afferent
      neurons.
AB  - Although primary afferent neurons express receptors for calcitonin gene-related
      peptide (CGRP), understanding of the cellular effects of these receptors is
      limited. We determined that CGRP receptors regulate gene transcription in primary
      afferent neurons through a cyclic AMP (cAMP)-dependent pathway. CGRP increased
      cAMP in neonatal dorsal root ganglion (DRG) neurons in a concentration-dependent
      manner that was blocked by the receptor antagonist CGRP(8-37). The response to
      CGRP also occurred in adult DRG cells. In contrast, CGRP did not alter the
      concentration of free intracellular calcium in neonatal or adult DRG neurons.
      Immunohistochemical data showed that one downstream effect of the cAMP signaling
      pathway was phosphorylation of cAMP response element binding (CREB) protein,
      suggesting that CGRP regulates gene expression. This interpretation was supported
      by evidence that CGRP increased CRE-dependent gene transcription in neurons
      transiently transfected with a CRE-luciferase DNA reporter construct. The effect
      of CGRP on gene transcription was inhibited by H89, myristoylated-protein kinase
      A inhibitor(14-22)-amide and U0126, indicating that protein kinase A and mitogen
      activated protein kinase/extracellular receptor kinase kinase are enzymes that
      mediate effects of CGRP on gene transcription. Therefore, CGRP receptors may
      regulate expression of proteins by primary afferent neurons during development
      and in response to tissue-damaging stimuli.

PMID- 15584919
TI  - Neurotrophin-3-induced production of nerve growth factor is suppressed in Schwann
      cells exposed to high glucose: involvement of the polyol pathway.
AB  - Development of hypesthesia, a loss of sensitivity to stimulation, is associated
      with impaired regeneration of peripheral sensory fibers, in which Schwann cells
      play a key role by secreting nerve growth factor (NGF). Recent clinical trials
      indicated that an inhibitor of aldose reductase (AR), the rate-limiting enzyme in
      the polyol pathway, significantly improved hypesthesia in diabetic patients. The
      fact that AR is localized in Schwann cells led us to investigate the role of the
      polyol pathway in NGF production of isolated Schwann cells. Among various
      endogenous factors examined, increased production of NGF was demonstrated in the
      cells treated with neurotrophin-3 (NT-3) for 24 h. NT-3-induced NGF production
      was significantly suppressed when cells were cultured in the medium containing
      high glucose. In these cells, the levels of glutathione (GSH) and cAMP-response
      element binding protein (CREB) were reduced, whereas the level of activated
      nuclear factor-kappaB (NF-kappaB) was elevated. These changes were abolished when
      an AR inhibitor fidarestat was included in the medium. NT-3-induced NGF
      production was further attenuated in the cells treated with an inhibitor of GSH
      synthesis. Together, the enhanced polyol pathway activity under high-glucose
      conditions seems to elicit reduced NT-3-induced NGF production in Schwann cells.
      Enhanced oxidative stress linked to the polyol pathway activity may mediate this
      process.

PMID- 15584920
TI  - Distinct promoters regulate tissue-specific and differential expression of
      kallikrein 6 in CNS demyelinating disease.
AB  - Kallikrein 6 is a serine protease expressed abundantly in normal adult human and
      rodent CNS, and therein is regulated by injury. In the case of CNS demyelinating
      disease, K6 expression in CNS occurs additionally in perivascular and parenchymal
      inflammatory cells suggesting a role in pathogenesis. Herein we describe two
      unique transcripts that occur within the human and mouse K6 genes that differ in
      their 5'-untranslated regions. These transcripts have identical translation
      initiation sites in exon 3, are expressed in a tissue-specific fashion and are
      differentially regulated in response to CNS injury. While the human and mouse 5'
      transcripts differ in sequence they are identical in genomic organization and
      tissue-specific expression. The most 5'-transcript, designated transcript 1,
      includes exon 1-7, and was detectable in all CNS regions, but not in any non-CNS
      tissues examined (spleen, thymus, liver, kidney, pancreas, submandibular gland
      and peripheral nerve). In contrast, transcript 2 lacks exon 1, but contains a
      unique sequence at the 5'-end of exon 2, designated exon 2A. Transcript 2 was
      expressed both in CNS and in each peripheral tissue. In a murine model of human
      CNS demyelinating inflammatory disease induced by Theiler's picornovirus, mouse
      K6 transcript 1 was up-regulated in brain and spinal cord at acute and more
      chronic phases of CNS inflammation and demyelination, while overall transcript 2
      expression was not significantly altered. However, in isolated splenocyte
      cultures, transcript 2 was up-regulated two-fold by cellular activation. Tissue
      specific expression patterns and differential regulation in CNS disease indicates
      that each K6 5'-transcript is probably regulated by unique promoter elements and
      may serve as a molecular target to treat inflammatory demyelinating disease.

PMID- 15584921
TI  - Clindamycin is neuroprotective in experimental Streptococcus pneumoniae
      meningitis compared with ceftriaxone.
AB  - In animal models of Streptococcus pneumoniae meningitis, rifampin is
      neuroprotective in comparison to ceftriaxone. So far it is not clear whether this
      can be generalized for other protein synthesis-inhibiting antimicrobial agents.
      We examined the effects of the bactericidal protein synthesis-inhibiting
      clindamycin (n = 12) on the release of proinflammatory bacterial components, the
      formation of neurotoxic compounds and neuronal injury compared with the standard
      therapy with ceftriaxone (n = 12) in a rabbit model of pneumococcal meningitis.
      Analysis of the CSF and histological evaluation were combined with microdialysis
      from the hippocampal formation and the neocortex. Compared with ceftriaxone,
      clindamycin reduced the release of lipoteichoic acids from the bacteria (p =
      0.004) into the CSF and the CSF leucocyte count (p = 0.011). This led to lower
      extracellular concentrations of hydroxyl radicals (p = 0.034) and glutamate (p =
      0.016) in the hippocampal formation and a subsequent reduction of extracellular
      glycerol levels (p = 0.018) and neuronal apoptosis in the dentate gyrus (p =
      0.008). The present data document beneficial effects of clindamycin compared with
      ceftriaxone on various parameters linked with the pathophysiology of pneumococcal
      meningitis and development of neuronal injury. This study suggests
      neuroprotection to be a group effect of bactericidal protein synthesis-inhibiting
      antimicrobial agents compared with the standard therapy with beta-lactam
      antibiotics in meningitis.

PMID- 15584922
TI  - Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active
      cargo proteins to neurones via unfolded translocation intermediates.
AB  - Multi-domain bacterial protein toxins are being explored as potential carriers
      for targeted delivery of biomolecules. Previous approaches employing isolated
      receptor binding subunits disallow entry into the cytosol. Strategies in which
      catalytic domains are replaced with cargo molecules are presumably inefficient
      due to co-operation of domains during the endosomal translocation step. Here, we
      characterize a novel transport vehicle in which cargo proteins are attached to
      the amino terminus of the full-length botulinum neurotoxin type D (BoNT/D). The
      intrinsic enzymatic activity of the neurotoxin allowed quantification of the
      efficacy of cargo delivery to the cytosol. Dihydrofolate reductase and BoNT type
      A (BoNT/A) light chain (LC) were efficiently conveyed into the cytosol, whereas
      attachment of firefly luciferase or green fluorescent protein drastically reduced
      the toxicity. Luciferase and BoNT/A LC retained their catalytic activity as
      evidenced by luciferin conversion or SNAP-25 hydrolysis in the cytosol of
      synaptosomes, respectively. Conformationally stabilized dihydrofolate reductase
      as cargo considerably decreased the toxicity indicative for the requirement of
      partial unfolding of cargo protein and catalytic domain as prerequisite for
      efficient translocation across the endosomal membrane. Thus, enzymatically
      inactive clostridial neurotoxins may serve as effective, safe carriers for
      delivering proteins in functionally active form to the cytosol of neurones.

PMID- 15584923
TI  - Effects of neonatal ventral hippocampal lesion in rats on stress-induced
      acetylcholine release in the prefrontal cortex.
AB  - Excitotoxic neonatal ventral hippocampus (NVH) lesions in rats result in
      characteristic post-pubertal hyper-responsiveness to stress and cognitive
      abnormalities analogous to those described in schizophrenia and suggestive of
      alterations in dopamine (DA) neurotransmission. Converging lines of evidence also
      point to dysfunctions in the cortical cholinergic system in neuropsychiatric
      disorders. In previous studies, we observed alterations in dopaminergic
      modulation of acetylcholine (Ach) release in the prefrontal cortex (PFC) in post
      pubertal NVH-lesioned rats. These two neurotransmitter systems are involved in
      the stress response as PFC release of DA and Ach is enhanced in response to some
      stressful stimuli. As adult NVH-lesioned rats are behaviorally more reactive to
      stress, we investigated the effects of NVH lesions on tail-pinch stress-induced
      Ach and DA release in the PFC. Using in vivo microdialysis, we observed that tail
      pinch stress resulted in significantly greater increases in prefrontal cortical
      Ach release in post-pubertal NVH-lesioned rats (220% baseline) compared with sham
      operated controls (135% baseline). Systemic administration of the D1-like
      receptor antagonist SCH 23390 (0.5 mg/kg i.p.) or the D2-like receptor antagonist
      haloperidol (0.2 mg/kg i.p.), as well as intra-PFC administration of the D2-like
      antagonist sulpiride (100 microm), reduced stress-induced Ach release in PFC of
      adult NVH-lesioned rats. By contrast, intra-PFC administration of SCH 23390 (100
      microm) failed to affect stress-induced Ach release in PFC of NVH-lesioned rats.
      Interestingly, using in vivo voltammetry, stress-induced stimulation of PFC DA
      release was found to be attenuated in adult NVH-lesioned rats. Taken together,
      these data suggest developmentally specific reorganization of prefrontal cortical
      cholinergic innervation notably regarding its regulation by DA neurotransmission.

PMID- 15584924
TI  - Identification of Tbr-1/CASK complex target genes in neurons.
AB  - Tbr-1, a neuron-specific T-box transcription factor, plays a critical role in
      brain development. Here, we performed a computational search using the non
      palindromic T-box binding sequence, namely the non-palindromic T-element, to
      determine the putative downstream target genes of Tbr-1. More than 20 identified
      genes containing the non-palindromic T-element in the 5' regulatory region were
      found expressed in brain. Luciferase reporter assays using cultured hippocampal
      neurons showed that overexpression of Tbr-1 and CASK-enhanced promoter activities
      of some of these putative target genes, including NMDAR subunit 2b (NR2b),
      glycine transporter, interleukin 7 receptor (IL-7R) and OX-2. Among these genes,
      NR2b promoter responded strongest to overexpression of Tbr-1 and CASK. Deletion
      of the non-palindromic T-elements from NR2b promoter impaired the induction by
      Tbr-1 and CASK. We also examined expression of these target genes in Tbr-1
      knockout mice, it was found that NR2b expression was consistently downregulated.
      Similarly, both RNA and protein expression levels of NMDAR subunit 1 (NR1), which
      also contains the non-palindromic T-elements in its 5' regulatory region, were
      reduced in Tbr-1 knockout mice. We suggest that Tbr-1/CASK protein complex
      regulates expression of these downstream target genes and thus modulates neuronal
      activity and function.

PMID- 15584925
TI  - STAT6 transcription factor binding sites with mismatches within the canonical 5'
      TTC...GAA-3' motif involved in regulation of delta- and mu-opioid receptors.
AB  - Opioid receptors are expressed in neuronal and immune cells and regulated in
      response to immunological processes. Herein, we demonstrate up-regulation of the
      delta-opioid receptor gene by interleukin-4 in immune cells (primary T and
      polymorphonuclear leukocytes, Jurkat E6 T cells), and in NG 108-15 neuronal
      cells. We identified an interleukin-4-responsive element at nt -671 on the murine
      gene promoter, to which the transcription factor STAT6 binds, as shown by
      reporter gene analysis and STAT6/DNA interaction studies in living cells with
      transcription factor decoy oligonucleotides. STAT6 normally binds to palindromic
      DNA motifs with a 5'-TTC...GAA-3' core. Notably, the delta-opioid receptor STAT6
      site (5'-TTC...GGA-3') is an imperfect palindrome with a mismatch within this
      core sequence. A systematic analysis of possible mismatch 5'-TTC...GAA-3' motifs
      revealed that STAT6 also binds to the sequence 5'-TTA...GAA-3'. This motif occurs
      as a polymorphism in the human mu-opioid receptor gene (Kraus et al. 2001 J.
      Biol. Chem 276, 43901-43908). We show that this mutated element has a
      significantly reduced STAT6 binding activity which correlates to its reduced
      interleukin (IL)-4 inducibility. In contrast, the non-canonical STAT6 site of the
      delta-opioid receptor binds STAT6 with similar high activity as a perfectly
      palindromic STAT6 site and is strongly inducible by IL-4.

PMID- 15584926
TI  - Blockade of nociceptin/orphanin FQ transmission in rat substantia nigra reverses
      haloperidol-induced akinesia and normalizes nigral glutamate release.
AB  - We recently showed that pharmacological blockade of nociceptin/orphanin FQ
      (N/OFQ) peptide (NOP) receptors located in the substantia nigra stimulates the
      nigrostriatal dopaminergic pathway and motor behavior (Marti et al. J. Neurosci.
      2004, 24, 6659-6666). To investigate whether such motor-stimulating action was
      dependent on functional dopaminergic transmission, the selective NOP receptor
      peptide antagonist [Nphe1,Arg14,Lys15]N/OFQ-NH2 (UFP-101) was microinjected into
      the substantia nigra reticulata of rats made cataleptic by systemic haloperidol
      administration. UFP-101 reduced haloperidol-induced akinesia as measured by
      immobility time in the bar test. UFP-101 also induced contralateral turning in
      cataleptic rats. To investigate the mechanisms involved in the anti-akinetic
      action of UFP-101, nigral glutamate release was monitored by microdialysis
      technique. The anti-akinetic action of UFP-101 correlated with normalization of
      nigral glutamate release, previously elevated by haloperidol injection. We
      conclude that endogenous N/OFQ in the substantia nigra sustains akinesia
      generated by impaired DA transmission and subthalamic nucleus overactivation. NOP
      receptor antagonists may be beneficial in the symptomatic therapy of
      parkinsonism, via normalization of subthalamonigral glutamatergic transmission.

PMID- 15584928
TI  - Potentiation by angiotensin II of spontaneous excitatory postsynaptic currents in
      rat supraoptic magnocellular neurones.
AB  - The physiological actions of angiotensin II in the supraoptic (SON) and
      paraventricular nuclei have been widely demonstrated, including the modulation of
      firing rate and release of arginine vasopressin and oxytocin. Here, we
      investigated whether angiotensin II modulates synaptic inputs into the SON. To do
      this, we measured spontaneous excitatory and inhibitory postsynaptic currents
      (EPSCs and IPSCs) from rat SON neurones in thin slice preparations using the
      whole-cell patch-clamp technique. Angiotensin II reversibly increased the
      frequency of spontaneous EPSCs in a dose-related manner without affecting the
      amplitude, indicating that angiotensin II potentiated EPSCs via a presynaptic
      mechanism. Angiotensin II-induced potentiation of EPSCs was unaffected in the
      presence of tetrodotoxin. On the other hand, angiotensin II did not cause
      significant effects on IPSCs. The potentiation of EPSCs by angiotensin II was
      potently suppressed by previous exposure to the angiotensin type 1 (AT1) receptor
      antagonist, losartan. Our results suggest that angiotensin II potentiates the
      excitatory synaptic inputs into SON neurones, via the AT1 receptors.

PMID- 15584929
TI  - Distribution and acute stressor-induced activation of corticotrophin-releasing
      hormone neurones in the central nervous system of Xenopus laevis.
AB  - In mammals, corticotrophin-releasing hormone (CRH) and related peptides are known
      to play essential roles in the regulation of neuroendocrine, autonomic and
      behavioural responses to physical and emotional stress. In nonmammalian species,
      CRH-like peptides are hypothesized to play similar neuroendocrine and neurocrine
      roles. However, there is relatively little detailed information on the
      distribution of CRH neurones in the central nervous system (CNS) of nonmammalian
      vertebrates, and there are currently no comparative data on stress-induced
      changes in CRH neuronal physiology. We used a specific, affinity-purified
      antibody raised against synthetic Xenopus laevis CRH to map the distribution of
      CRH in the CNS of juvenile South African clawed frogs. We then analysed stress
      induced changes in CRH immunoreactivity (CRH-ir) throughout the CNS. We found
      that CRH-positive cell bodies and fibres are widely distributed throughout the
      brain and rostral spinal cord of juvenile X. laevis. Strong CRH-immunoreactivity
      (ir) was found in cell bodies and fibres in the anterior preoptic area (POA, an
      area homologous to the mammalian paraventricular nucleus) and the external zone
      of the median eminence. Specific CRH-ir cell bodies and fibres were also
      identified in the septum, pallium and striatum in the telencephalon; the
      amygdala, bed nucleus of the stria terminalis and various hypothalamic and
      thalamic nuclei in the diencephalon; the tectum, torus semicircularis and
      tegmental nuclei of the mesencephalon; the cerebellum and locus coeruleus in the
      rhombencephalon; and the ventral horn of the rostral spinal cord. To determine if
      exposure to an acute physical stressor alters CRH neuronal physiology, we exposed
      juvenile frogs to shaking/handling and conducted morphometric analysis. Plasma
      corticosterone was significantly elevated by 30 min after exposure to the
      stressor and continued to increase up to 6 h. Morphometric analysis of CRH-ir
      after 4 h of stress showed a significant increase in CRH-ir in parvocellular
      neurones of the anterior preoptic area, the medial amygdala and the bed nucleus
      of the stria terminalis, but not in other brain regions. The stress-induced
      increase in CRH-ir in the POA was associated with increased Fos-like
      immunoreactivity (Fos-LI), and confocal microscopy showed that CRH-ir colocalized
      with Fos-LI in a subset of Fos-LI-positive neurones. Our results support the view
      that the basic pattern of CNS CRH expression arose early in vertebrate evolution
      and lend further support to earlier studies suggesting that amphibians may be a
      transitional species for descending CRH-ergic pathways. Furthermore, CRH neurones
      in the frog brain exhibit changes in response to a physical stressor that
      parallel those seen in mammals, and thus are likely to play an active role in
      mediating neuroendocrine, behavioural and autonomic stress responses.

PMID- 15584930
TI  - Low temperature stimulates alpha-melanophore-stimulating hormone secretion and
      inhibits background adaptation in Xenopus laevis.
AB  - It is well-known that alpha-melanophore-stimulating hormone (alpha-MSH) release
      from the amphibian pars intermedia (PI) depends on the light condition of the
      animal's background, permitting the animal to adapt the colour of its skin to
      background light intensity. In the present study, we carried out nine experiments
      on the effect of low temperature on this skin adaptation process in the toad
      Xenopus laevis, using the skin melanophore index (MI) bioassay and a
      radioimmunoassay to measure skin colour adaptation and alpha-MSH secretion,
      respectively. We show that temperatures below 8 degrees C stimulate alpha-MSH
      secretion and skin darkening, with a maximum at 5 degrees C, independent of the
      illumination state of the background. No significant stimulatory effect of low
      temperature on the MI and alpha-MSH plasma contents was noted when the experiment
      was repeated with toads from which the neurointermediate lobe (NIL) had been
      surgically extirpated. This indicates that low temperature stimulates alpha-MSH
      release from melanotrope cells located in the PI. An in vitro superfusion study
      with the NIL demonstrated that low temperature does not act directly on the PI. A
      possible role of the central nervous system in cold-induced alpha-MSH release
      from the PI was tested by studying the hypothalamic expression of c-Fos (as an
      indicator for neuronal activity) and the coexistence of c-Fos with the regulators
      of melanotrope cell activity, neuropeptide Y (NPY) and thyrotrophin-releasing
      hormone (TRH), using double fluorescence immunocytochemistry. Upon lowering
      temperature from 22 degrees C to 5 degrees C, in white-adapted animals c-Fos
      expression decreased in NPY-producing suprachiasmatic-melanotrope-inhibiting
      neurones (SMIN) in the ventrolateral area of the suprachiasmatic nucleus (SC) but
      increased in TRH-containing neurones of the magnocellular nucleus. TRH is known
      to stimulate melanotrope alpha-MSH release. We conclude that temperatures around
      5 degrees C inactivate the SMIN in the SC and activate TRH-neurones in the
      magnocellular nucleus, resulting in enhanced alpha-MSH secretion from the PI,
      darkening the skin of white-adapted X. laevis.

PMID- 15584931
TI  - Inter-relationships between the secretory dynamics of thyrotrophin-releasing
      hormone, thyrotrophin and prolactin in periovulatory mares: effect of
      hypothyroidism.
AB  - We used our nonsurgical technique for collecting pituitary venous blood to relate
      the dynamics of thyrotrophin-releasing hormone (TRH) secretion to the secretion
      patterns of both prolactin and thyrotrophin in periovulatory mares, either
      euthyroid (n = 5) or made hypothyroid by treatment with propyl-thiouracil (n =
      5). Pituitary venous blood was collected continuously and divided into 1-min
      aliquots for 4 h. To test the effect of dopamine on the relationship between
      secretion patterns, sulpiride, a selective D2 receptor antagonist, was given i.m.
      after 2 h of sampling. Thorough testing of the model and blood collection
      procedure revealed no sites of TRH loss. Hypothyroidism increased the mean
      secretion rates of TRH (P = 0.04) and thyrotrophin (P < 0.0001) but not
      prolactin. Sulpiride increased prolactin secretion rates in hypothyroid (P <
      0.0001) and control (P = 0.007) mares, but did not alter TRH or thyrotrophin
      secretion rates. In both groups of mares, all three hormones were secreted
      episodically but not rhythmically. In both groups, the secretion pattern of TRH
      was almost always significantly related to that of thyrotrophin, as assessed by
      cross correlation and cross approximate entropy (ApEn) analysis. However, the
      degree of linear correlation was weak, with only 14% (hypothyroid) or 8%
      (controls) of the variation in thyrotrophin secretion rates attributable to TRH.
      Prolactin and TRH secretion patterns before sulpiride were coupled on cross ApEn
      analysis in both groups, and the minute-to-minute secretion rates of the two
      hormones were correlated in four hypothyroid and three euthyroid mares. Overall,
      the small, but significant, degree of association between TRH and prolactin was
      similar to that between TRH and thyrotrophin. In hypothyroid mares, sulpiride
      increased (P = 0.02) the synchrony between TRH and prolactin patterns. We
      conclude that in horses: (i) little TRH degradation occurs during passage through
      the pituitary or in blood after 1 h at 37 degrees C; (ii) TRH is not the major
      factor controlling minute-to-minute fluctuations in either thyrotrophin or
      prolactin; and (iii) reducing two strongly inhibitory inputs (i.e. dopamine and
      thyroid hormones) may magnify the stimulatory effect of TRH on prolactin
      secretion.

PMID- 15584932
TI  - Photoperiod affects neuronal nitric oxide synthase and aggressive behaviour in
      male Siberian hamsters (Phodopus sungorus).
AB  - Many nontropical animals display physiological and behavioural changes in
      response to seasonal environmental cues including photoperiod (day length). Male
      Siberian hamsters (Phodopus sungorus) housed in short photoperiod undergo
      testicular regression accompanied by reduced circulating testosterone and
      decreased reproductive behaviour. By contrast to the majority of small mammals
      studied, aggressive behaviour is elevated in short-day Siberian hamsters when
      blood testosterone concentrations are not detectable. Because gonadal steroid
      hormones influence neuronal nitric oxide synthase (nNOS), and this enzyme has
      been implicated in aggressive behaviour, we hypothesized that nNOS expression
      would be decreased in short-day male Siberian hamsters and negatively correlated
      with the display of territorial aggression. Adult male Siberian hamsters were
      individually housed in either long (LD 16:8 h) or short (LD 8:16 h) photoperiods
      for 10 weeks. Hamsters were assigned to one of two categories by assessing
      testicular volume and plasma testosterone values: (i) photoperiodic responsive
      (i.e. regressed testes and low testosterone concentrations) or (ii) photoperiodic
      nonresponsive (i.e. testes size and circulating testosterone concentrations
      equivalent to hamsters maintained in long days). At week 10, aggression was
      assessed using a resident-intruder test. Latency to initial attack, frequency of
      attacks and duration of total attacks were recorded during a 10-min aggression
      trial. Brains were collected immediately after behavioural testing and stained
      for nNOS expression using immunohistochemistry. All short day-housed hamsters
      were significantly more aggressive than long-day animals, regardless of gonadal
      size or testosterone concentrations. Short-day animals, both reproductively
      responsive and nonresponsive morphs, also had significantly less nNOS
      immunoreactive cells in the anterior and basolateral amygdaloid areas and
      paraventricular nuclei compared to long-day hamsters. Together, these results
      suggest that seasonal aggression in male Siberian hamsters is regulated by
      photoperiod, through mechanisms that are likely independent from gonadal steroid
      hormones.

PMID- 15584933
TI  - Circulating ghrelin levels and central ghrelin receptor expression are elevated
      in response to food deprivation in a seasonal mammal (Phodopus sungorus).
AB  - Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor
      (GHSR). However, the functional interaction of ligand and receptor is not very
      well understood. We demonstrate that GHSR mRNA is up-regulated after food
      deprivation (48 h) in the hypothalamic arcuate nucleus and ventromedial nucleus
      of the seasonal Siberian hamster, Phodopus sungorus. This increase is accompanied
      by a two-fold elevation of circulating ghrelin concentration. Chronic changes in
      feeding state imposed by food restriction over a period of 12 weeks during long
      day-length induced increased GHSR gene expression, whereas food restriction for 6
      weeks had no effect. Phodopus sungorus reveals remarkable seasonal changes in
      body weight, fat mass and circulating leptin levels. Ghrelin is generally
      regarded as having opposing effects on appetite and body weight with respect to
      those exhibited by leptin. However, our study revealed that seasonal adaptations
      were not accompanied by changes in either GHSR gene expression or circulating
      ghrelin concentration. Therefore, we suggest that ghrelin only plays a minor role
      in modulating long-term seasonal body weight cycles. Our findings imply that
      ghrelin predominantly acts as a short-term regulator of feeding.

PMID- 15584934
TI  - Mechanisms of N-methyl-D-aspartate receptor inhibition by melatonin in the rat
      striatum.
AB  - N-methyl-D-aspartate (NMDA) receptor activation comprises multiple regulatory
      sites controlling Ca2+ influx into the cell. NMDA-induced increases in
      intracellular [Ca(+2)] lead to nitric oxide (NO) production through activation of
      neuronal NO synthase (nNOS). Melatonin inhibits either glutamate or NMDA-induced
      excitation, but the mechanism of this inhibition is unknown. In the present
      study, the mechanism of melatonin action in the rat striatum was studied using
      extracellular single unit recording of NMDA-dependent neuronal activity with
      micro-iontophoresis. Melatonin inhibited neuronal excitation produced by either
      NMDA or L-arginine. The effects of both NMDA and L-arginine were blocked by nitro
      L-arginine methyl ester, suggesting that nNOS participates in responses to NMDA.
      However, excitation of NMDA-sensitive neurones induced by the NO donor sodium
      nitroprusside was only slightly modified by melatonin. Melatonin iontophoresis
      also counteracted excitation induced by tris(2-carboxyethyl)phosphine
      hydrochloride, showing that the redox site of the NMDA receptor may be a target
      for melatonin action. The lack of effects of the membrane melatonin receptor
      ligands luzindole, 4-phenyl-2-propionamidotetralin and 5-methoxycarbonylamino-N
      acetyltryptamine, and the nuclear melatonin ligand, CGP 52608, a thiazolidine
      dione, excluded the participation of known membrane and nuclear receptors for
      melatonin. The data suggest that inhibition of NMDA-dependent excitation by
      melatonin involves both nNOS inhibition and redox site modulation.

PMID- 15584935
TI  - Estimation of parameters for a mathematical model of growth hormone secretion.
AB  - Here, we describe partial calibration of a parsimonious mathematical model of
      growth hormone (GH) secretion. From first principles, we derived a model of the
      effects on GH secretion from pituitary somatotrophs of stimulation by GH
      releasing factor (GRF) or GH secretagogue, and of inhibition by somatostatin. We
      obtained a concise model by collapsing the many processes of the signal
      transduction cascade into a single step broadly reflecting the initial binding of
      GRF to its receptors. In the model, GH secretion is proportional to the rate of
      binding of GRF to activatable receptors. Desensitization occurs because of
      reduction of free receptors/available effector units, and resensitization occurs
      as those lost are replaced. This replacement is speeded up in the presence of
      somatostatin, which also inhibits GH secretion by reducing the constant of
      proportionality between the rate of GH secretion and the rate of GRF binding. We
      derived simple mathematical equations for the rate of GH secretion and cumulative
      secretion. Using these, we tested the model against data obtained from
      experiments performed in vitro, and made it quantitative using rigorous
      statistical approaches to optimize parameter estimates. The behaviour of the
      calibrated model matches experimental observations closely.

PMID- 15584936
TI  - BANs to rINNS.
AB  - Medical errors are increasingly being highlighted as an unnecessary cause of
      morbidity and mortality. Such situations are increasingly likely to occur if each
      country has its own improved name for each individual drug, particularly as
      healthcare staff are becoming increasingly mobile across the world.
      Standardization of drug names will help reduce the risk of such errors. However
      because of the change between BANs and rINNS there is potential for short-term
      problems. Healthcare staff need to be aware of such problems to try and minimize
      the damage they could potentially cause. In the longer term these name changes
      will hopefully prevent errors from occurring.

PMID- 15584937
TI  - Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with
      diabetes experiencing unstable angina or non-ST segment elevation myocardial
      infarction. What have we learned in the last 10 years?
AB  - Coronary disease accounts for the majority of deaths among patients with diabetes
      and the thrombotic milieu accelerated by diabetes results in unstable angina
      (UA), non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment
      elevation myocardial infarction (STEMI) or death. Upstream use of a glycoprotein
      IIb/IIIa (GP IIb/IIIa) inhibitor with percutaneous coronary intervention (PCI) as
      part of an early invasive approach is preferred. However substantial numbers of
      patients present to rural or non-teaching hospitals without immediate access to a
      catheterization laboratory. Enhanced GP IIb/IIIa receptor mobilization, TXA2
      production and platelet activation together present an extensive thrombotic
      challenge that may not be overcome with current doses of GP IIb/IIIa inhibitors
      when used without PCI. Heterogeneity of platelet aggregometric analysis may have
      identified GP IIb/IIIa doses used in clinical trials that may not fully overcome
      the thrombotic challenge in patients with diabetes. GUSTO-IV ACS failed to
      demonstrate a difference in mortality when used without PCI. The PURSUIT trial
      provided evidence that eptifibatide decreases death or non-fatal myocardial
      infarction (MI) in the main group and in the diabetic subgroup. Reductions in
      this primary endpoint were driven by the reduction in non-fatal MI. The PRISM and
      PRISM-PLUS trials demonstrated a reduction in death, MI or refractory ischaemia
      at 48 h or 7 days in the main cohort but not specifically in patients with
      diabetes. Data supporting use of GP IIb/IIIa inhibitors are inconsistent, raising
      the question of whether these agents should be used at all without PCI.
      Variability in experimental methodology of platelet aggregometry and selection of
      anticoagulant used during dose finding studies may have generated doses that are
      insufficient to overcome the thrombotic burden. A new marker of active
      inflammation, sCD40L is found to be upregulated at subtherapeutic doses of GP
      IIb/IIIa inhibitors, suggesting that rebound inflammatory processes may partially
      account for absence of clear evidence of benefit with some GP IIb/IIIa inhibitors
      in patients with diabetes experiencing UA/NSTEMI.

PMID- 15584938
TI  - Pharmacokinetics of gabapentin in paediatric patients with uncontrolled seizures.
AB  - PURPOSE: The pharmacokinetics of gabapentin in paediatric patients with
      uncontrolled seizures was studied. METHODS: Thirteen paediatric patients (mean
      age: 9.4 years) with uncontrolled partial seizures were included. Patients
      received gabapentin orally until doses were individualized to 9.6-39.8 mg/kg/day.
      Blood samples were obtained just prior to the dose and over 8 h after gabapentin
      was administered in the fasting state. The plasma concentration of gabapentin was
      measured by a high-performance liquid chromatography assay. Pharmacokinetic
      parameters for gabapentin were determined by non-compartment methods using
      multivariate regression analysis. RESULTS: Data from nine patients were suitable
      for pharmacokinetic analysis. The C(max) from 0.9 to 5.8 microg/mL (mean: 2.6 +/-
      1.7 microg/mL) and T(max) from 0.5 to 2.0 h (mean: 1.6 +/- 1.0 h). The apparent
      clearance (Cl/F) ranged from 0.12 to 1.12 L/h/kg (mean: 0.50 +/- 0.29 L/h/kg),
      and the elimination half-life from 3.2 to 12.2 h (mean: 5.5 +/- 0.8 h). Five
      patients experienced moderate (n = 4) to severe (n = 1) aggressive behaviour and
      another gained weight on gabapentin. CONCLUSIONS: Our data suggests that
      gabapentin pharmacokinetics can vary substantially among paediatric patients.
      Gabapentin was well tolerated in patients with uncontrolled partial seizures up
      to 6 months of therapy.

PMID- 15584939
TI  - Restoration of flow following haemodialysis catheter thrombus. Analysis of rt-PA
      infusion in tunnelled dialysis catheters.
AB  - PROBLEM: Urokinase and streptokinase are commonly used thrombolytic agents for
      obstructed central venous catheters. Although proven to be efficacious, these
      agents have the potential to induce fibrin breakdown and streptokinase cannot be
      used repeatedly because of its allergenic nature. Published evidence suggests
      that Urokinase is safe and effective (>70% efficacy for catheter installation)
      and that Tissue-type plasminogen activator (rt-PA) can achieve as much as 98%
      success. OBJECTIVE: To describe our experience with and our protocol for the use
      of rt-PA as an alternative agent for catheter thrombolysis. DESIGN: Investigation
      of a cohort of haemodialysis patients with tunnelled central venous catheter
      (SPCVC) placed between December 2001 to August 2003 and who developed catheter
      thrombus (female, n = 8: male, n = 12). Each patient was given an infusion of
      between 1 and 2 mg rt-PA/h for 4 h. The dose was dependent on partial or total
      line obstruction. The technical success of rt-PA is defined as returning catheter
      blood flow to >250 mL/min for a 4-h period. FINDINGS: Twenty patients required 57
      infusions in 38 lumens between 01/01/02 to 01/09/03. For completely blocked lines
      rt-PA was infused at 2 mg/h for 4 h achieving 85% success rate. For inadequate
      flow (<250 mL/min) rt-PA was infused at 1 mg/h for 4 h achieving an 88% success
      rate. CONCLUSION: Rt-PA administered at 2 mg/h for blocked lines effectively
      restores haemodialysis catheter patency, and at 1 mg/h for sluggish lines is also
      effective in restoring blood flow through catheters.

PMID- 15584940
TI  - An assessment of dose-uniformity of samples delivered from paediatric oral
      droppers.
AB  - BACKGROUND AND OBJECTIVES: To assess the accuracy and precision of delivery from
      containers containing oral drops, both under optimal laboratory conditions and
      during use by volunteers using a variety of real pharmaceutical products and
      specially prepared fluids. METHODS: The effects of the physical properties
      (viscosity, surface tension, fluid density) of fluids and the angle of a dropper
      upon the accuracy and precision of dispensing were investigated under standard
      laboratory conditions. Dose delivery was then assessed using a number of
      volunteers who were either given no instructions on the use of containers or were
      instructed to hold the droppers vertically. RESULTS: Viscosity, surface tension,
      fluid density and residual volume had little or no effect upon the volume of
      liquid delivered by a dropper clamped in the vertical position. However, when the
      angle of the dropper was moved towards 45 degrees from the vertical, the volume
      dispensed declined and became more variable to a point where the requirements of
      the European Pharmacopoeia were no longer fulfilled. This finding applied to a
      variety of products. When volunteers used the same droppers manually, the mean
      volumes dispensed were lower than when the droppers were vertically clamped and
      the variability was greater. It appeared that these problems were associated with
      volunteers failing to hold the dropper vertically and the precision and accuracy
      were indeed increased if the volunteers were instructed as to how the dropper
      should be held. The results from volunteers were more precise and accurate with
      the most viscous of the fluids tested and it was speculated that this may have
      been because the volunteers could more easily use the droppers vertically as
      there was less fear of dispensing too many drops. CONCLUSIONS: The key factor in
      achieving satisfactory dispensing from droppers is to ensure that the dropper is
      held vertically and this should form the basis of instructions to patients.
      Formulators should consider increasing the viscosity of prepared dropper
      solutions to reduce further errors in dose.

PMID- 15584941
TI  - Pharmaceutical care and community pharmacists' understanding of bisphosphonate
      dosing information.
AB  - OBJECTIVES: To evaluate pharmacists' knowledge of approved dosing information for
      cyclic etidronate, alendronate and risedronate in the treatment of postmenopausal
      osteoporosis; and to assess its relationship to demographic and pharmaceutical
      care factors. DESIGN: Fax-back questionnaire to evaluate pharmacists' knowledge
      of approved bisphosphonate dosing information and their involvement in
      pharmaceutical/patient care activities through independent indices. SETTING:
      Community pharmacies in both urban and rural settings in British Columbia.
      PARTICIPANTS: Pharmacies surveyed with 22% response rate (163 pharmacists), 47%
      male and 54% owners/managers. Most were independent (31%) or volunteer chain
      (28%) pharmacies. MEASUREMENTS AND MAIN RESULTS: Mean bisphosphonate dosing
      knowledge score was 76 +/- 11% (mean +/- SD). Mean scores (+/-SD) for questions
      pertaining to alendronate (92 +/- 13%) were higher than risedronate (81 +/- 26%)
      and etidronate (48 +/- 19). Pharmacists were least familiar with approved dosing
      instructions regarding the lack of need to remain upright after etidronate
      dosing, spacing out of etidronate from food/antacids/calcium/vitamins, and
      whether risedronate may be taken at bedtime. Factors found to affect pharmacists'
      bisphosphonate knowledge scores included employment in higher volume pharmacies
      and greater number of years in practice. Pharmacists in the upper tertile of
      pharmaceutical care index scores had similar bisphosphonate knowledge scores to
      those delivering less pharmaceutical care. Pharmacist gender, being
      owner/manager, and continuing education hours were not significantly associated
      with higher knowledge or pharmaceutical care scores. CONCLUSIONS: There is a wide
      range of knowledge of bisphosphonate dosing and delivery of pharmaceutical care
      amongst community pharmacists surveyed. Given the importance of proper
      bisphosphonate dosing to optimize drug absorption and to minimize toxicity,
      pharmacist education should be a priority.

PMID- 15584942
TI  - Prescribing patterns in high-need Health Authority populations: how does an
      ethnically mixed composition affect volume and cost?
AB  - BACKGROUND: Prescribing is the most common therapeutic intervention in primary
      care, and there is substantial variation in prescribing practice across England.
      We investigate broad patterns of prescribing across Health Authorities in
      England, concentrating on ethnically diverse populations. METHODS: Initially we
      examined the association between a number of prescribing indicators from the
      Prescribing Support Unit Prescribing Toolkit and 'Needs Profiles'. We then
      considered whether the observed patterns of prescribing were appropriate, that
      is, could be largely explained by variations in the prevalence of a medical
      condition for which the corresponding group of drugs would be prescribed.
      RESULTS: The volume and cost of prescribing was generally lower in more
      ethnically diverse Health Authority populations when compared with more elderly
      or deprived populations. There was a significant negative association between
      ethnic composition and net-ingredient-cost per patient of cardiovascular drugs,
      but this disappeared upon adjusting for mortality from coronary heart disease.
      CONCLUSIONS: The volume and cost of prescribing was generally lower in more
      ethnically diverse Health Authority populations relative to other high-need
      population profiles. Further work on this subject matter is merited, particularly
      if individual level data is available.

PMID- 15584943
TI  - Rational pharmacotherapy in the diabetic hypertension: analysis-prescribing
      patterns in a general hospital in Taiwan.
AB  - OBJECTIVES: To examine prescribing at a 2800-bed hospital, also providing
      ambulatory services for 9000 visits per day, with a view to assessing the extent
      to which it followed international guidelines for treating diabetic hypertension.
      METHOD: Patients receiving antidiabetic and antihypertensive drugs concomitantly
      during the 4-week study period were included. RESULT: Of the 5015 eligible
      patients, most received combination antidiabetic therapy. Oral antidiabetic
      agents used alone or in combination included (in descending order) metformin,
      glibenclamide, gliclazide, glipizide, glimepiride and alpha-glucosidase
      inhibitors. Gliclazide accounted for most of the oral antidiabetic drug
      expenditure. Sulfonylurea plus metformin was the most popular regimen.
      Prescriptions for long-acting sulfonylureas did not differ between elderly and
      younger patients. For blood pressure control, calcium-channel blockers were most
      commonly used alone and overall, although current guidelines suggest that they
      should be second-line treatments. Inappropriate use of immediate-release
      nifedipine was noted. The combination, atenolol >100 mg/day and
      hydrochlorothiazide 50 mg/day (or an equivalent) were extensively used. Among
      54.7% patients treated with combination antihypertensives, calcium-channel
      blockers and an angiotensin-converting enzyme inhibitor were most commonly used.
      CONCLUSION: Most diabetic hypertensive patients were treated with combination
      therapy for glucose and blood pressure control. Prescriptions for
      antihypertensive drugs often differed from current guidelines, especially in the
      choice of agents and their combinations.

PMID- 15584944
TI  - Genetic polymorphism of CYP2D6 in patients with cardiovascular disease -- a
      cohort study.
AB  - BACKGROUND: Cardiovascular diseases are complex diseases that are influenced by
      both environmental and genetic factors. CYP2D6 found in the brain and the heart
      is involved in the metabolism of many environmental and some endogenous
      substances and neurotransmitters responsible for maintaining homeostasis. This
      raises an interesting hypothesis that it may have a role in the development of or
      protection against cardiovascular diseases. OBJECTIVE: To study the distribution
      of genotypes of CYP2D6 among patients with cardiovascular diseases in Malaysia.
      METHOD: We obtained DNA from 128 patients who were followed up for cardiovascular
      diseases. Polymerase chain reaction-based methods were used to determine common
      CYP2D6 alleles. RESULTS: One hundred and twenty-eight patients were enrolled.
      Most of the patients also had concurrent illnesses. Eleven genotypes were
      identified in the patients and 41% carried CYP2D6*1/*10. The second most common
      genotype was homozygous for the wild type gene, followed by homozygous
      CYP2D6*10/*10 at 14.48 %. A small percentage of the patients were heterozygous
      CYP2D6*1/*4. One patient was genotyped homozygous CYP2D6*4/*4 predicting a poor
      metabolizer prevalence of 0.78% (95% CI +/- 1.52%). Analysis using Hardy-Weinberg
      equilibrium showed that all of the gnotypes were consistent with equilibrium
      except for CYP2D6*1/*10 (chi(2); P < 0.05). CONCLUSION: Our study suggests a
      possible involvement of CYP2D6 genotypes in cardiovascular system diseases, which
      need to be validated by further studies.

PMID- 15584945
TI  - Increased digitalis-like immunoreactive substances in neonatal plasma measured
      using fluorescence polarization immunoassay.
AB  - OBJECTIVE: To better define the reported increased digitalis-like immunoreactive
      substances (DLIS) in neonatal plasma, we studied the relation among plasma DLIS
      level, blank intensity (BLK-I) value at FPIA measurement and plasma total
      bilirubin level. METHODS: The DLIS levels were measured in 10 neonates with or
      without jaundice and 10 infants in good health, using fluorescence polarization
      immunoassay (FPIA) and microparticle enzyme immunoassay (MEIA). BLK-I value and
      plasma total bilirubin level were also measured simultaneously. RESULTS: In
      neonates with jaundice, DLIS using FPIA, BLK-I and total bilirubin level were
      0.58 +/-0.13 ng/mL, 2598 +/- 408, and 17.98 +/- 1.13 mg/dL, respectively, before
      phototherapy, and 0.33 +/-0.06 ng/mL, 1886 +/- 237, and 15.16 +/- 2.07 mg/dL
      after phototherapy. Corresponding values in neonates without jaundice were (DLIS:
      0.34 +/-0.04 ng/mL; BLK-I: 1,764 +/- 278; total bilirubin: 10.37 +/- 4.54 mg/dL);
      in healthy infants (0.12 +/-0.06 ng/mL, 400.7 +/- 4.6 and 0.42 +/- 0.13 mg/dL,
      respectively) and in healthy volunteers (0.10 +/-0.07 ng/mL, 403.1 +/- 8.4, and
      0.58 +/- 0.30 mg/dL, respectively). Using MEIA, DLIS was not detected in 10
      neonates, 10 infants and 20 healthy volunteers. CONCLUSIONS: A fluorescent
      compound related to bilirubin increased the BLK-I value in the measurement of
      neonatal plasma using FPIA. The fluorescence was not the result of endogenous
      digitalis-like factors.

PMID- 15584946
TI  - Pectin in pig nutrition, a comparative review.
AB  - A comprehensive review is given on pectin effects in pigs. Its effects on feed
      passage and digestion in the small intestine, the composition of ileal digesta
      and fermentation in the colon are described. Pectins promote fermentation at the
      terminal ileum and in the first part of the colon. It is shown, that pectin
      opposite to cellulose is degraded to high extents in the colon. Dietetic effects
      in relation to composition of ileocaecal digesta, endogenous secretions,
      buffering and pH-stability, high fermentability of organic matter in the colon
      and resulting volatile fatty acids (VFA) in the cranial part of the colon and
      even its possible interactions to colonization of the gut by infectious bacteria
      are described. Pectin effects concerning volume of the intestinal tract,
      distribution of VFA and lactic acid, role of endogenous secretions are described.
      The negative effect of pectins on praecaecal digestibility, their high
      degradation rates in the large intestine and consequences for their dietetic
      effects are discussed.

PMID- 15584947
TI  - Field evaluation of the efficacy of a probiotic containing Bacillus licheniformis
      and Bacillus subtilis spores, on the health status and performance of sows and
      their litters.
AB  - The aim of this study was to assess the efficacy of BioPlus 2B, a probiotic
      containing Bacillus licheniformis and Bacillus subtilis spores, on the health
      status and productivity of sows and their litters. A total of 109 gilts and sows
      were allocated into two experimental groups, as follows: untreated controls (UC)
      and BioPlus 2B (same feeding as the UC group plus BioPlus 2B) at a dose of 400
      g/ton of feed (equal to 1.28 x 10(6) viable spores/g of feed). Treatment started
      from the day of allocation (14 days prior to the expected farrowing) up to the
      weaning day. Homogeneity of the groups was satisfied with regard to the parity.
      From the results it was evident that BioPlus 2B supplementation of the feed
      improved gilt/sow performance as shown by: (i) the increase of sow feed
      consumption during the first 14 days postpartum and (ii) the decrease of sow
      weight loss during the suckling period. Certain blood and milk parameters were
      significantly improved, as shown by higher serum cholesterol and total lipids
      concentrations and higher milk fat and protein content at mid-suckling period. As
      a consequence, a positive effect was also noticed as regard litter health and
      performance characteristics in terms of: (i) decrease in piglet diarrhoea score,
      (ii) decrease in pre-weaning mortality thus leading to increase in the number of
      weaned piglets per litter and (iii) increase in piglet body weight at weaning.
      Moreover, BioPlus 2B tended to improve the health status and fertility of sows
      demonstrating: (i) tendency to a lower proportion of sows with Mastitis-Metritus
      Agalactia (MMA) problems and (ii) lower proportion of sows returning to oestrus.

PMID- 15584948
TI  - Changes in selected serum parameters of broiler chicken fed supplemental
      chromium.
AB  - The present study was conducted to evaluate the effect of chromium (Cr) from Cr
      yeast on the growth performance and total cholesterol, high-density lipoprotein
      (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose,
      total protein and Cr concentration in the serum of broiler chicken. The birds
      were fed a control diet or a control diet supplemented with Cr at a level of 300,
      500 microg/kg Cr. The supplementation of 500 mug/kg Cr increased body weight,
      weight gain and feed efficiency (p < 0.05). In addition, supplementation with Cr
      decreased the serum total cholesterol, LDL cholesterol (p < 0.05), triglycerides
      (p < 0.05) and glucose (p < 0.05) concentrations whereas serum HDL cholesterol
      increased. Serum total protein and serum Cr concentration slightly but not
      significantly increased in both Cr groups. The study suggest that Cr
      supplementation particularly at 500 microg/kg Cr from Cr yeast can influence on
      carbohydrate and lipid metabolism of broiler chicken and can be used as additives
      in animal diet but it still needs more investigations.

PMID- 15584949
TI  - Rumen odd and branched chain fatty acids in relation to in vitro rumen volatile
      fatty acid productions and dietary characteristics of incubated substrates.
AB  - A first aim of this batch in vitro experiment (21 h) was to use changes in odd
      and branched chain fatty acid (OBCFA) patterns to suggest shifts in microbial
      populations, associated with four types of incubated whole dairy cow diets.
      Principal component analysis suggested higher dietary starch increased the
      proportion of C15:0 and C17:0, whereas increased neutral detergent fibre content
      was positively related to anteiso C15:0 concentrations, which is in agreement
      with the importance of these fatty acids in respectively amylolytic and
      cellulolytic bacteria. A second aim of the experiment was to relate rumen
      volatile fatty acid proportions to OBCFA by principal component regression and to
      compare these relations with predictions based on diet proximate composition. The
      R2 values achieved for the regressions between acetate, propionate and butyrate,
      and OBCFA were 79.6%, 86.6% and 84.9% respectively. Moreover, in the current
      study, predictions of the rumen fermentation pattern showed higher R2 (p < 0.01)
      when based on OBCFA compared with proximate feed composition. If relations
      persist in vivo, there could be scope for milk OBCFA to predict the supply of
      specific rumen nutrients.

PMID- 15584950
TI  - The influence of calcium intake on phosphorus digestibility in mature ponies.
AB  - Literature data show conflicting results on the effect of feeding high calcium
      (Ca) levels on phosphorus (P) digestibility in ponies. None of the studies
      reported involved a dose response as to the effect of Ca intake on apparent P
      digestibility while keeping P intake constant. Thus, the influence of high
      dietary Ca level on apparent P digestibility was studied in balance trials by
      feeding six mature ponies three different Ca levels against a constant P intake.
      The ponies received 148, 316 and 535 mg Ca/kg BW/day with the low, intermediate
      and high Ca diet. Phosphorus intake was approximately 125 mg P/kg BW and
      magnesium (Mg) intake was approximately 35 mg Mg/kg BW/day. The intermediate and
      high Ca level decreased apparent digestibility, renal excretion and retention of
      P when compared with the low Ca level. However, apparent digestibility and renal
      excretion of P were not different between the intermediate and high Ca level. The
      high Ca level resulted in a retention of 66 mg Ca/kg BW/day. The percentage
      apparent digestibility of Ca was lower for the intermediate and high Ca level
      compared with the low Ca level. Magnesium digestibility was not affected by high
      dietary Ca level. In practice, high absolute amounts of Ca should be prevented
      especially when low amounts of P are fed; P digestibility will be depressed and a
      negative P balance may occur.

PMID- 15584951
TI  - Loss of TIP1;1 aquaporin in Arabidopsis leads to cell and plant death.
AB  - Arabidopsis TIP1;1 (gammaTIP) is a member of the tonoplast family of aquaporins
      (AQP). Using RNA interference (RNAi) we reduced TIP1;1 to different extent in
      various lines. When most severely affected, miniature plants died, a phenotype
      partially complemented by the TIP1;1 homolog McMIP-F. Less severely affected
      lines produced small plants, early senescence, and showed lesion formation. The
      relative water content in TIP1;1 RNAi plants was not significantly affected.
      Global expression profiling suggested a disturbance in carbon metabolism in RNAi
      lines with upregulated transcripts for functions in carbon acquisition and
      respiration, vesicle transport, signaling and transcription, and radical oxygen
      stress. Metabolite profiles showed low glucose, fructose, inositol, and threonic,
      succinic, fumaric, and malic acids, but sucrose levels were similar to WT.
      Increased amounts were found for raffinose and several unknown compounds. TIP1;1
      RNAi plants also contained high starch and apoplastic carbohydrate increased. A
      GFP-TIP1;1 fusion protein indicated tonoplast location in spongy mesophyll cells,
      and high signal intensity in palisade mesophyll associated with vesicles near
      plastids. Signals in vascular tissues were strongest not only in vesicle-like
      structures but also outlined large vacuoles. Compromised routing of carbohydrate
      and lack of sucrose provision for cell-autonomous functions seems to characterize
      this RNAi phenotype. We suggest a function for TIP1;1 in vesicle-based metabolite
      routing through or between pre-vacuolar compartments and the central vacuole.
      Phenotype and expression characteristics support a view of TIP1;1 functioning as
      a marker for vesicles that are targeted to the central vacuole.

PMID- 15584952
TI  - Comparison of TRY and the closely related At1g01380 gene in controlling
      Arabidopsis trichome patterning.
AB  - A screen of activation-tagged Arabidopsis lines resulted in the identification of
      At1g01380, which encodes a small R3 single repeat MYB gene, as a negative
      regulator of trichome initiation. Plants that overexpress this gene have fewer
      trichomes. The gene is closely related to the previously identified negative
      regulator TRY, and has a similar pattern of expression as TRY in developing
      leaves. As previously shown for TRY, At1g01380 protein can inhibit the
      interaction between the positive trichome regulators GL1 and GL3, and likely
      limits trichome initiation via this inhibition. While TRY and At1g01380 are
      closely related, they are not completely functionally equivalent. When placed
      under the transcriptional control of the TRY promoter, At1g01380 can only
      partially rescue the try mutant. Interestingly, Atg01380 is highly expressed in
      gl3-sst trichomes, while TRY expression is greatly reduced. The mutation in gl3
      sst causes a reduced interaction between the GL1 and GL3 proteins and results in
      fewer leaf trichomes that develop in clusters. The differential expression of TRY
      and At1g01380 in this mutant can be used to explain how its altered trichome
      pattern in gl3-sst [corrected] is generated.

PMID- 15584953
TI  - Overexpression of tomato LeAGP-1 arabinogalactan-protein promotes lateral
      branching and hampers reproductive development.
AB  - LeAGP-1 is a glycosylphosphatidylinositol (GPI)-anchored arabinogalactan-protein
      (AGP) in tomato (Lycopersicon esculentum). Patterns of mRNA expression and
      protein localization for LeAGP-1 indicate that it likely functions in certain
      aspects of plant growth and development. To elucidate LeAGP-1 function(s),
      transgenic tomato plants expressing enhanced green fluorescent protein (GFP)
      fused to LeAGP-1 [GFP-LeAGP-1] or two LeAGP-1 variants, one lacking the C
      terminal GPI-anchor domain [GFP-LeAGP-1DeltaC] and the other lacking the lysine
      rich domain [GFP-LeAGP-1DeltaK], under the control of the CaMV35S promoter were
      produced using Agrobacterium-mediated transformation. Transgenic T0 and T1 lines
      with high levels of both GFP-LeAGP-1 mRNA and protein: (i) were significantly
      shorter; (ii) were highly branched; (iii) produced more flower buds, but most of
      these flowers did not mature, resulting in less fruit production; and (iv)
      produced seeds that were significantly smaller than normal seeds. Overexpression
      of LeAGP-1DeltaK had a similar or even more pronounced effect on plant vegetative
      and reproductive growth, while the effect of LeAGP-1DeltaC overexpression on
      plant reproduction was minimal. These results indicate that the GPI anchor is
      critical for LeAGP-1 function. As the phenotype of GFP-LeAGP-1 overexpressing
      transgenic plants is similar to that of cytokinin-overproducing plants, mRNA
      expression patterns of LeAGP-1 under different hormone treatments were examined.
      Cytokinins upregulated LeAGP-1 mRNA expression, while auxins and ABA inhibited
      LeAGP-1 mRNA expression. Based on these results, GPI-anchored LeAGP-1 most likely
      functions in plant growth and development in concert with auxin/cytokinin
      signaling.

PMID- 15584954
TI  - The tomato carotenoid cleavage dioxygenase 1 genes contribute to the formation of
      the flavor volatiles beta-ionone, pseudoionone, and geranylacetone.
AB  - Volatile terpenoid compounds, potentially derived from carotenoids, are important
      components of flavor and aroma in many fruits, vegetables and ornamentals.
      Despite their importance, little is known about the enzymes that generate these
      volatiles. The tomato genome contains two closely related genes potentially
      encoding carotenoid cleavage dioxygenases, LeCCD1A and LeCCD1B. A quantitative
      reverse transcriptase-polymerase chain reaction analysis revealed that one of
      these two genes, LeCCD1B, is highly expressed in ripening fruit (4 days post
      breaker), where it constitutes 0.11% of total RNA. Unlike the related neoxanthin
      cleavage dioxygenases, import assays using pea chloroplasts showed that the
      LeCCD1 proteins are not plastid-localized. The biochemical functions of the
      LeCCD1 proteins were determined by bacterial expression and in vitro assays,
      where it was shown that they symmetrically cleave multiple carotenoid substrates
      at the 9,10 (9',10') positions to produce a C14 dialdehyde and two C13
      cyclohexones that vary depending on the substrate. The potential roles of the
      LeCCD1 genes in vivo were assessed in transgenic tomato plants constitutively
      expressing the LeCCD1B gene in reverse orientation. This over-expression of the
      antisense transcript led to 87-93% reductions in mRNA levels of both LeCCD1A and
      LeCCD1B in the leaves and fruits of selected lines. Transgenic plants exhibited
      no obvious morphological alterations. High-performance liquid chromatography
      analysis showed no significant modification in the carotenoid content of fruit
      tissue. However, volatile analysis showed a > or =50% decrease in beta-ionone (a
      beta-carotene-derived C13 cyclohexone) and a > or =60% decrease in geranylacetone
      (a C13 acyclic product likely derived from a lycopene precursor) in selected
      lines, implicating the LeCCD1 genes in the formation of these important flavor
      volatiles in vivo.

PMID- 15584955
TI  - Arabidopsis glucosyltransferase UGT74B1 functions in glucosinolate biosynthesis
      and auxin homeostasis.
AB  - Glucosinolates are a class of secondary metabolites with important roles in plant
      defense and human nutrition. Here, we characterize a putative UDP
      glucose:thiohydroximate S-glucosyltransferase, UGT74B1, to determine its role in
      the Arabidopsis glucosinolate pathway. Biochemical analyses demonstrate that
      recombinant UGT74B1 specifically glucosylates the thiohydroximate functional
      group. Low Km values for phenylacetothiohydroximic acid (approximately 6 microm)
      and UDP-glucose (approximately 50 microm) strongly suggest that thiohydroximates
      are in vivo substrates of UGT74B1. Insertional loss-of-function ugt74b1 mutants
      exhibit significantly decreased, but not abolished, glucosinolate accumulation.
      In addition, ugt74b1 mutants display phenotypes reminiscent of auxin
      overproduction, such as epinastic cotyledons, elongated hypocotyls in light-grown
      plants, excess adventitious rooting and incomplete leaf vascularization. Indeed,
      during early plant development, mutant ugt74b1 seedlings accumulate nearly
      threefold more indole-3-acetic acid than the wild type. Other phenotypes,
      however, such as chlorosis along the leaf veins, are likely caused by
      thiohydroximate toxicity. Analysis of UGT74B1 promoter activity during plant
      development reveals expression patterns consistent with glucosinolate metabolism
      and induction by auxin treatment. The results are discussed in the context of
      known mutations in glucosinolate pathway genes and their effects on auxin
      homeostasis. Taken together, our work provides complementary in vitro and in vivo
      evidence for a primary role of UGT74B1 in glucosinolate biosynthesis.

PMID- 15584956
TI  - Endogenous salicylic acid protects rice plants from oxidative damage caused by
      aging as well as biotic and abiotic stress.
AB  - Salicylic acid (SA) is a key endogenous signal that mediates defense gene
      expression and disease resistance in many dicotyledonous species. In contrast to
      tobacco and Arabidopsis, which contain low basal levels of SA, rice has two
      orders of magnitude higher levels of SA and appears to be insensitive to
      exogenous SA treatment. To determine the role of SA in rice plants, we have
      generated SA-deficient transgenic rice by expressing the bacterial salicylate
      hydroxylase that degrades SA. Depletion of high levels of endogenous SA in
      transgenic rice does not measurably affect defense gene expression, but reduces
      the plant's capacity to detoxify reactive oxygen intermediates (ROI). SA
      deficient transgenic rice contains elevated levels of superoxide and H2O2, and
      exhibits spontaneous lesion formation in an age- and light-dependent manner.
      Exogenous application of SA analog benzothiadiazole complements SA deficiency and
      suppresses ROI levels and lesion formation. Although an increase of conjugated
      catechol was detected in SA-deficient rice, catechol does not appear to
      significantly affect ROI levels based on the endogenous catechol data and
      exogenous catechol treatment. When infected with the blast fungus (Magnaporthe
      grisea), SA-deficient rice exhibits increased susceptibility to oxidative bursts
      elicited by avirulent isolates. Furthermore, SA-deficient rice is hyperresponsive
      to oxidative damage caused by paraquat treatment. Taken together, our results
      strongly suggest that SA plays an important role to modulate redox balance and
      protect rice plants from oxidative stress.

PMID- 15584957
TI  - Analysis of the aliphatic monomer composition of polyesters associated with
      Arabidopsis epidermis: occurrence of octadeca-cis-6, cis-9-diene-1,18-dioate as
      the major component.
AB  - Although the surface waxes from Arabidopsis thaliana leaves and stems have been
      thoroughly characterized, the monomer composition of the polyesters of the
      cuticular membrane has not been analyzed. Delipidated Arabidopsis leaves or
      stems, when depolymerized under conditions to cleave polyesters, produced typical
      omega-hydroxy fatty acid cutin monomers such as 16-hydroxy-palmitate, 10,16
      dihydroxy-palmitate and 18-hydroxy-9,10-epoxy-stearate. However, the major
      monomer was octadeca-cis-6, cis-9-diene-1,18-dioate, with lesser amounts of
      octadec-cis-9-ene-1,18-dioate and hexadeca-1,16-dioate. These dicarboxylates were
      found predominantly in epidermal peels from Arabidopsis stems and are therefore
      likely to be associated with the cuticular membrane. They were also found in
      analyses of canola leaves but were absent in tomato and apple fruit cutins. In
      the fad2-1 mutant line of Arabidopsis, which has reduced levels of linoleate and
      linolenate and elevated oleate in cytosolic phospholipids, the amount of octadeca
      cis-6, cis-9-diene-1,18-dioate was 50% reduced, with a concomitant increase in
      octadec-cis-9-ene-1,18-dioate. In a fatb-ko line of Arabidopsis, where the
      availability of cytosolic palmitate is impaired, there was an 80% loss of C16
      monomers and a compensating increase in C18 monomers. The presence of substantial
      amounts of dicarboxylates in cuticular membranes is unexpected. High amounts of
      aliphatic dicarboxylates are usually considered as an indicator of suberin, and
      are reported only as very minor components of cutin. The high level of
      polyunsaturation is also unusual in cuticles; saturated fatty acid monomers
      usually predominate, with lesser amounts of monounsaturates. These novel findings
      for Arabidopsis demonstrate that a broad range of monomer compositions are
      possible for polyesters of the epidermis.

PMID- 15584958
TI  - Role of chloroplast trienoic fatty acids in plant disease defense responses.
AB  - Trienoic fatty acids (TAs) are the major polyunsaturated fatty acid species in
      the membrane lipids in plant cells. TAs are crucial for the adaptation to abiotic
      stresses, especially low- or high-temperature stress. We show that TAs in
      chloroplast membrane lipids are involved in defense responses against avirulent
      bacterial pathogens. Avirulent pathogen invasion of plants induces a transient
      production of reactive oxygen intermediates (ROI), programmed cell death and
      subsequent disease resistance. The Arabidopsis fad7fad8 mutation, which prevents
      the synthesis of TAs in chloroplast lipids, caused the reduction in ROI
      accumulation in leaves inoculated with Pseudomonas syringae pv. tomato DC3000
      (avrRpm1). Linolenic acid, the most abundant TA, activated the NADPH oxidase that
      is responsible for ROI generation. TAs were transferred from chloroplast lipids
      to extrachloroplast lipids coincident with ROI accumulation after inoculation
      with Pst DC3000 (avrRpm1). Furthermore, the fad7fad8 mutant exhibited reduced
      cell death and was compromised in its resistance to several avirulent P. syringae
      strains. These results suggest that TAs derived from chloroplast lipids play an
      important role in the regulation of plant defense responses.

PMID- 15584959
TI  - Gene shuffling-generated and natural variants of the tomato resistance gene Cf-9
      exhibit different auto-necrosis-inducing activities in Nicotiana species.
AB  - Tomato Cf genes encode membrane-bound proteins with extracellular leucine-rich
      repeats, and confer resistance to the fungal tomato pathogen Cladosporium fulvum,
      and a hypersensitive response (HR) to C. fulvum-derived race-specific elicitors.
      Several Cf genes, including Cf-4 and Cf-9, are members of the highly homologous
      Hcr9 (homologues of C. fulvumresistance gene Cf-9) gene family. Hcr9s evolve
      mainly by sequence exchange between paralogues, by which novel Cf genes may be
      generated. To mimic this aspect of natural evolution, we generated chimeras
      between multiple Hcr9s in vitro by gene shuffling. The shufflants were tested for
      novel specificities by transient expression in Nicotiana benthamiana. Many
      shufflants induced an HR in the absence of fungal elicitors and were designated
      auto-activators. We also identified two natural Hcr9 auto-activators in the wild
      tomato species Lycopersicon peruvianum, which induced an HR upon expression in N.
      benthamiana. The Hcr9 auto-activators exhibit different auto-necrosis-inducing
      specificities in five selected species of the Nicotiana genus, and they were
      shown to function in the same signalling pathway as Cf-9. Auto-activating alleles
      of nucleotide binding site-leucine-rich repeat genes and the protein kinase Pto
      were previously described. The auto-activators described here, belonging to the
      Cf-like structural class of resistance genes, shed light on this important
      phenotype and may be used as tools to unravel the mechanisms by which this class
      of resistance proteins function.

PMID- 15584960
TI  - Concurrent interactions of heme and FLU with Glu tRNA reductase (HEMA1), the
      target of metabolic feedback inhibition of tetrapyrrole biosynthesis, in dark-
      and light-grown Arabidopsis plants.
AB  - The regulation of tetrapyrrole biosynthesis in higher plants has been attributed
      to metabolic feedback inhibition of Glu tRNA reductase by heme. Recently, another
      negative regulator of tetrapyrrole biosynthesis has been discovered, the FLU
      protein. During an extensive second site screen of mutagenized flu seedlings a
      suppressor of flu, ulf3, was identified that is allelic to hy1 and encodes a heme
      oxygenase. Increased levels of heme in the hy1 mutant have been implicated with
      inhibiting Glu tRNA reductase and suppressing the synthesis of delta
      aminolevulinic acid (ALA) and Pchlide accumulation. When combined with hy1 or
      ulf3 upregulation of ALA synthesis and overaccumulation of protochlorophyllide in
      the flu mutants were severely suppressed supporting the notion that heme
      antagonizes the effect of the flu mutation by inhibiting Glu tRNA reductase
      independently of FLU. The coiled-coil domain at the C-terminal end of Glu tRNA
      reductase interacts with FLU, whereas the N-terminal site of Glu tRNA reductase
      that is necessary for the inhibition of the enzyme by heme is not required for
      this interaction. The interaction with FLU is specific for the Glu tRNA reductase
      encoded by HEMA1 that is expressed in photosynthetically active tissues. FLU
      seems to be part of a second regulatory circuit that controls chlorophyll
      biosynthesis by interacting directly with Glu tRNA reductase not only in
      etiolated seedlings but also in light-adapted green plants.

PMID- 15584961
TI  - Mutations in PMR5 result in powdery mildew resistance and altered cell wall
      composition.
AB  - Powdery mildews and other obligate biotrophic pathogens are highly adapted to
      their hosts and often show limited host ranges. One facet of such host
      specialization is likely to be penetration of the host cell wall, a major barrier
      to infection. A mutation in the pmr5 gene rendered Arabidopsis resistant to the
      powdery mildew species Erysiphe cichoracearum and Erysiphe orontii, but not to
      the unrelated pathogens Pseudomonas syringae or Peronospora parasitica. PMR5
      belongs to a large family of plant-specific genes of unknown function. pmr5
      mediated resistance did not require signaling through either the salicylic acid
      or jasmonic acid/ethylene defense pathways, suggesting resistance in this mutant
      may be due either to the loss of a susceptibility factor or to the activation of
      a novel form of defense. Based on Fourier transform infrared analysis, the pmr5
      cell walls were enriched in pectin and exhibited a reduced degree of pectin
      modification relative to wild-type cell walls. In addition, the mutant had
      smaller cells, suggesting a defect in cell expansion. A double mutant with pmr6
      (defective in a glycosylphosphatidylinositol-anchored pectate lyase-like gene)
      exhibited a strong increase in total uronic acid content and a more severe
      reduction in size, relative to the single mutants, suggesting that the two genes
      affect pectin composition, either directly or indirectly, via different
      mechanisms. These two mutants highlight the importance of the host cell wall in
      plant-microbe interactions.

PMID- 15584962
TI  - AtMYB32 is required for normal pollen development in Arabidopsis thaliana.
AB  - AtMYB32 gene is a member of the R2R3 MYB gene family coding for transcription
      factors in Arabidopsis thaliana. Its expression pattern was analysed using
      Northern blotting, in situ hybridization and promoter-GUS fusions. AtMYB32 is
      expressed in many tissues, but most strongly in the anther tapetum, stigma
      papillae and lateral root primordia. AtMYB32-GUS was induced in leaves and stems
      following wounding, and in root primordia by auxin. T-DNA insertion populations
      were screened and two insertion mutants were identified, both of which were
      partially male sterile, more than 50% of the pollen grains being distorted in
      shape and lacking cytoplasm. AtMYB4 is closely related to AtMYB32 and represses
      the CINNAMATE 4-HYDROXYLASE gene. Distorted pollen grains were produced in both
      AtMYB4 insertion mutant and overexpression lines. In an AtMYB32 insertion mutant,
      the transcript levels of the DIHYDROFLAVONOL 4-REDUCTASE and ANTHOCYANIDIN
      SYNTHASE genes decreased while the level of the CAFFEIC ACID 0-METHYLTRANSFERASE
      transcript increased. Change in the levels of AtMYB32 and AtMYB4 expression may
      influence pollen development by changing the flux along the phenylpropanoid
      pathways, affecting the composition of the pollen wall.

PMID- 15584963
TI  - The ubiquitin ligase XBAT32 regulates lateral root development in Arabidopsis.
AB  - Ubiquitin-mediated protein modification plays a key role in many cellular signal
      transduction pathways. The Arabidopsis gene XBAT32 encodes a protein containing
      an ankyrin repeat domain at the N-terminal half and a RING finger motif. The
      XBAT32 protein is capable of ubiquitinating itself. Mutation in XBAT32 causes a
      number of phenotypes including severe defects in lateral root production and in
      the expression of the cell division marker CYCB1;1::GUS. The XBAT32 gene is
      expressed abundantly in the vascular system of the primary root, but not in newly
      formed lateral root primordia. Treatment with auxin increases the expression of
      XBAT32 in the primary root and partially rescues the lateral root defect in
      xbat32-1 mutant plants. Thus, XBAT32 is a novel ubiquitin ligase required for
      lateral root initiation.

PMID- 15584964
TI  - A novel reporter for intrachromosomal homoeologous recombination in Arabidopsis
      thaliana.
AB  - A reporter system using engineered introns as recombination substrates in the
      uidA (GUS) gene has been developed and characterized in Arabidopsis thaliana. The
      non-coding nature of the recombination substrate has allowed us to monitor
      recombination events between duplicated copies of the intron that are either
      identical (homologous recombination) or harbour sequence polymorphisms
      (homoeologous recombination). The effects of substrate length and divergence on
      the frequency of recombination events were examined. A positive correlation
      between substrate length and somatic recombination frequency was found as the
      frequency of recombination increased 183-fold when the recombination substrate
      was lengthened from 153 to 589 bp. The existence of 11 polymorphisms in a 589-bp
      recombination substrate (1.9% sequence divergence) led to an almost 10-fold
      reduction in the frequency of recombination. This result demonstrates that
      relatively modest levels of sequence divergence can substantially reduce the
      frequency of recombination in plants. A molecular analysis of recombination
      products revealed that the recombination junctions are more frequent in the
      central segment of the recombination substrate.

PMID- 15584965
TI  - B-Lymphocytes activated by CD40 ligand induce an antigen-specific anti-tumour
      immune response by direct and indirect activation of CD8(+) T-cells.
AB  - In this report, we describe the ability of CD40-ligand (CD40L)-activated, antigen
      loaded B-cells to initiate antigen-specific anti-tumour immune responses in vivo.
      Mice immunized by means of intravenous administration of CD40L-activated B-cells
      loaded with an MHC class-I-binding peptide, and challenged with a tumour cell
      line expressing the same class-I epitope, showed a marked delay in tumour growth,
      compared to non-immunized controls or to mice receiving either freshly isolated B
      cells or B-cells activated with lipopolysaccharide or interleukin-4. The ability
      of CD40L-activated B-cells to induce antigen-specific T-cell activation appeared
      to be through a combination of cross-presentation of antigen from activated B
      cells to resident antigen-presenting cells and direct T-cell activation by the
      administered B-cells themselves. Immunization with CD40L-activated B-cells may,
      therefore, represent a means by which to stimulate anti-tumour CD8(+) T-cell
      responses in vivo.

PMID- 15584966
TI  - A dual role for interferon-gamma in the pathogenesis of Sjogren's syndrome-like
      autoimmune exocrinopathy in the nonobese diabetic mouse.
AB  - Sjogren's syndrome-like autoimmune exocrinopathy (AEC) in the nonobese diabetic
      (NOD) mouse progresses from a preimmune phase to an immune phase, resulting in
      dry mouth and/or dry eyes. In the present study, the impact of the prototypical T
      helper type 1 cytokine, interferon-gamma (IFN-gamma), on the onset of AEC was
      investigated using both the IFN-gamma and the IFN-gamma receptor gene knockout
      mice, NOD.IFN-gamma(-/-) and NOD.IFN-gammaR(-/-), respectively. Neither the
      NOD.IFN-gamma(-/-) nor the NOD.IFN-gammaR(-/-) mice exhibited increased acinar
      cell apoptosis and abnormal salivary protein expression, typically observed in
      parental NOD mice prior to disease. Without these preimmune phase abnormalities,
      NOD.IFN-gamma(-/-) and NOD.IFN-gammaR(-/-) mice showed no subsequent autoimmune
      responses against the salivary glands at 20 weeks. Interestingly, real-time
      polymerase chain reaction and electrophoretic gel mobility shift assays suggested
      that IFN-gamma and STAT1, as well as the transcriptional activity of STAT1 in NOD
      glands, were increased at birth. Unlike the neonatal submandibular glands of NOD
      or NOD-scid mice that show abnormal glandular morphogenesis at birth, the
      submandibular glands of the newly constructed congenic strain, NOD-scid.IFN
      gamma(-/-), were found to be normal. Taken together, IFN-gamma appears to play a
      critical role not only during the later immune phase of AEC, but also the early
      preimmune phase, independent of effector functions of immune cells. How exactly
      IFN-gamma functions during this period remains speculative.

PMID- 15584967
TI  - Activation of human umbilical vein endothelial cells leads to relocation and
      release of high-mobility group box chromosomal protein 1.
AB  - The nuclear protein high-mobility group box chromosomal protein 1 (HMGB1) was
      recently described to act as a pro-inflammatory cytokine and as a late mediator
      of severe sepsis and septic shock. The protein is released from monocytes in
      response to endotoxin and activates monocytes and endothelial cells through
      nuclear factor kappa B. We have previously demonstrated that the B-box of HMGB1
      mediates a pro-inflammatory effect on endothelial cells including the
      upregulation of cell-adhesion molecules and release of interleukin (IL)-8 and
      granulocyte colony-stimulating factor. Here, we report that HMGB1 is released
      from human umbilical vein endothelial cells (HUVEC) in response to
      lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-alpha. A nuclear
      relocation of HMGB1 to the cytoplasm was seen at 4 h. Subsequently, high amounts
      of HMGB1 could be seen in the supernatants from stimulated cells after 16 h. It
      was also observed that the pro-inflammatory activity of HMGB1 is sensitive to
      dexamethasone. Interestingly, the HMGB1-induced TNF-alpha release from monocytes
      could be inhibited by either the A-box of the protein or the p38 inhibitor CNI
      1493, but neither had any inhibitory effects on the HMGB1-dependent upregulation
      of cell-adhesion molecules on HUVEC. Altogether, these results suggest that HUVEC
      may be an important source of HMGB1 secretion in response to systemic infection
      and that endothelial cells and monocytes may use different signalling pathways.

PMID- 15584968
TI  - Characterization of splenic glycosaminoglycans accumulated in vivo in
      experimentally induced amyloid-susceptible and amyloid-resistant mice.
AB  - The pathogenesis of the amyloid deposition diseases is poorly understood. The
      CE/J mouse, which is naturally protected from amyloid A (AA) protein amyloidosis,
      has provided a tool to study mechanisms that may be implicated in amyloid
      deposition diseases by means of comparison of findings with those in an AA
      susceptible mouse strain. We have compared proteoglycan/glycosaminoglycan
      accumulation in vivo in amyloid-protected CE/J mouse strain and in AA-susceptible
      CBA/J mouse strain in homeostasis and when injected with amyloid-inducing agents.
      Results indicate that there is an overall increase in
      [(35)S]proteoglycan/glycosaminoglycan accumulation in the spleens of both strains
      of mice, but with a specific increase in heparan sulfate in only CBA/J mouse
      spleens that are rich in amyloid. Further, we report the absence of heparan
      sulfate in the splenic perifollicular areas of amyloid-free CE/J mouse, whereas
      in the amyloid-laden CBA/J mouse there is co-localization of heparan sulfate with
      the AA deposits. We have also examined the glycosaminoglycan disaccharide
      products in both these strains of mice for their sulfation positions and found no
      differences in the disaccharide composition of chondroitin/dermatan sulfate and
      heparan sulfate isolated from the control CBA/J and control CE/J mice. There were
      no differences in chondroitin/dermatan sulfate in both strains after experimental
      induction. However, analysis of the heparan sulfate disaccharides by means of
      capillary high-performance liquid chromatography linked to microelectrospray
      ionization time-of-flight mass spectrometry indicated that the disaccharide
      composition of the splenic heparan sulfate obtained from the treated CBA/J mice
      that had developed amyloid was markedly different from that obtained from the
      control CBA/J mice and the treated amyloid-resistant CE/J mice. These findings
      suggest that unique heparan sulfates play a fundamental role in the pathogenesis
      of amyloid.

PMID- 15584969
TI  - Serum concentration of the growth medium markedly affects monocyte-derived
      dendritic cells' phenotype, cytokine production profile and capacities to
      stimulate in MLR.
AB  - We have investigated how the maturation of monocyte-derived dendritic cells (Mo
      DC) is affected by the serum concentration of the culture medium. Day 6 DC
      cultured in 1% human serum were a heterogeneous population of CD1a(-) and CD1a(+)
      DC that were separated by flow sorting. In contrast, Mo-DC generated in 10% human
      serum formed a homogenous population of CD1a(-) cells. Other phenotypically
      immature characteristics also varied, and three subsets were still
      distinguishable upon maturation in LPS. Furthermore, CD1a(-) DC and CD1a(+) DC
      from 1% culture conditions were excellent stimulators in MLR, while DC cultured
      in 10% serum were poor stimulators. Similarly, different cytokine profiles of the
      three subsets were identified. DC cultured in 1% serum had low expression of
      interleukin-12 (IL-12) p40 and IL-10 mRNA at day 6. Upon maturation, expression
      of IL-12 p40 mRNA was upregulated in CD1a(+) DC, whereas the level remained
      relatively low in CD1a(-) DC. In contrast, DC cultured in 10% had high levels of
      IL-10 mRNA at day 6 that was downregulated upon maturation. We conclude that the
      differentiation of monocytes into DC is significantly influenced by the serum
      concentration of the growth medium with effects on phenotype, cytokine profile
      and stimulatory activity.

PMID- 15584970
TI  - Differential regulation of MHC class-I-restricted and unrestricted cytotoxicity
      by the Us3 protein kinase of herpes simplex virus-1.
AB  - Modulation of cytotoxic responses by viral immunoevasins plays an important role
      in the establishment of latent and persistent viral infections. Together with MHC
      class-I-restricted CD8T-lymphocytes, non-MHC-restricted natural killer (NK) and
      lymphokine-activated killer (LAK) cells participate in this anti-viral control.
      The Us3 protein kinase of herpes simplex virus-1 (HSV-1) inhibits CD8T-cell
      cytotoxicity, which correlates with the inhibition of granzyme-B (GrB)-induced
      activation of pro-apoptotic Bid. We have investigated the effect of Us3 on NK and
      LAK cytotoxicity, because these effectors are believed to share common mechanisms
      for inducing cell death. We show that, in contrast to their lower sensitivity to
      CD8T-cell lysis, HSV-1-infected cells are lysed by NK cells or LAK cells as
      efficiently as the uninfected controls. Both CD8T and NK/LAK effectors were
      dependent on the activity of GrB and were efficiently blocked by means of
      treatment with a GrB inhibitor. However, unlike CD8T cells, LAK cells and NK
      cells failed to induce Bid cleavage, suggesting that various GrB downstream
      targets be involved in the induction of cell lysis. This finding explains their
      various sensitivities to viral modulation, which is likely to be important for
      the respective role of MHC-restricted and non-restricted effectors in the control
      of HSV-1 infection.

PMID- 15584971
TI  - Kinetics of glycosaminoglycan deposition in splenic AA amyloidosis induced in
      mink.
AB  - The kinetics of splenic glycosaminoglycan (GAG) expression in mink has been
      investigated during the course of AA amyloid induction, i.e. at 3 to 6 weeks of
      lipopolysaccharide (LPS) treatment. Splenic amyloid was demonstrated by means of
      Congo red staining in five of 19 LPS-treated mink. Chondroitin/dermatan sulfate
      (CS/DS), as well as heparan sulfate proteoglycans (HSPG), was extracted from
      amyloid and control spleens. Independently of the presence of amyloid, the total
      amount of splenic GAGs increased with the duration of LPS treatment, and an HSPG
      population was found confined to the LPS-treated spleens. The differential
      expression of various PG and GAG epitopes in mink spleen was investigated with
      the help of immunohistochemistry. The amyloid deposits were shown to contain GAG
      chains of CS and HS, and the core proteins of DSPG decorin and the HSPGs perlecan
      and agrin. Decorin and perlecan were shown in normal spleens localized to the
      splenic ellipsoids, an early target for AA amyloid deposition. The constitutive
      expression of PGs at predilection sites for amyloid deposition and their
      increased expression in the tissues developing amyloidosis at these early stages
      show that PGs are available for the formation and deposition of AA amyloid.

PMID- 15584972
TI  - Interleukin-15, as interferon-gamma, induces the killing of Leishmania infantum
      in phorbol-myristate-acetate-activated macrophages increasing interleukin-12.
AB  - The potential leishmanicidal activity of interleukin-15 (IL-15) was examined
      while priming with the cytokine phorbol-myristate-acetate (PMA)-activated
      macrophages and infecting them with Leishmania infantum parasites. The activation
      of macrophage cultures with IL-15 determined a significant anti-leishmanial
      activity, comparable with that induced by interferon-gamma (IFN-gamma). The
      killing of Leishmania in macrophages primed with IL-15, as well as with IFN
      gamma, was followed by an increase in the IL-12 synthesis. The neutralization of
      IL-15 or IFN-gamma, by specific monoclonal antibodies (MoAb) caused a significant
      reduction in leishmanicidal activity. Furthermore, in PMA-activated macrophages,
      the neutralization of IL-12 production by a specific anti-IL-12 MoAb reduced
      leishmanicidal activity induced by IL-15 and IFN-gamma. Data indicate that IL-15
      could have a role as an activator of leishmanicidal activity, directly or
      indirectly, by inducing IL-12 production.

PMID- 15584973
TI  - Immunological analysis in paediatric HIV patients at different stages of the
      disease.
AB  - There are only few clinical studies on complement in well-defined (or
      characterized) paediatric HIV patients. Aim of this study was to evaluate the
      complement system and immunoglobulins in HIV-infected children and to correlate
      data to stage of disease. Blood samples of 127 HIV-infected children (11-134
      months; 62 male : 65 female) were collected in order to evaluate humoral
      immunity. The patients were classified according to CDC clinical (N-asymptomatic;
      A-mild symptoms such as common recurrent infections; B-moderate symptoms such as
      Candidiasis and herpes infections, meningitis, sepsis and anaemia; C-severe
      symptoms such as opportunistic infections and neoplasia) and with respect to
      immunological criteria (T CD4(+) cell count). Analysis of complement system
      included the classical (CH50), alternative (APH50) pathway activities and plasma
      concentrations of mannan-binding lectin (MBL), of the C4 allotypic variants C4A
      and C4B. (ELISA), and of the C3 split product C3d (rocket immunoeletrophoresis).
      Immunodiagnosis also included CD4(+) and CD8(+) lymphocyte count and
      immunoglobulin concentrations. Complement activation and consumption was observed
      in all patients correlating with disease activity. Activated classical and
      alternative pathways and elevated C3d were significantly correlated with
      immunologic category 3. C3d levels were also significantly correlated with
      immunologic category 1. Undetectable CH50 and APH50 were found in two (group C)
      and 10 patients (n = 2, A = 2, B = 2, C = 4), respectively. Low MBL values were
      found in 13/127 but without correlation to disease severity. Undetectable C4B
      levels were observed in three patients, favouring the diagnosis of a complete
      deficiency. Although not related to clinical symptomatology, a strong ongoing
      complement activation can be observed in all stages of HIV infection. In contrast
      to earlier reports MBL could not be considered as a risk factor for HIV.

PMID- 15584974
TI  - Reduction of soluble complement receptor 2/CD21 in systemic lupus erythomatosus
      and Sjogren's syndrome but not juvenile arthritis.
AB  - A soluble form of the complement receptor CD21 (sCD21) is shed from the
      lymphocyte surface. The amount of sCD21 in serum may modulate immunity as sCD21
      levels are correlated with several clinical conditions. We report here the serum
      levels of sCD21 in juvenile arthritis (JA), systemic lupus erythematosus (SLE)
      and Sjogren's syndrome (SS). Using enzyme-linked immunosorbent assay, we
      determined sCD21 levels in SLE, SS and JA patients. Mann-Whitney test for
      nonparametric two-tail P value was performed to obtain statistical significance.
      Cytometrical analysis of synovial fluid leucocytes of JA patients was done on a
      FACSsort. While sCD21 levels in SLE and SS are reduced to levels previously found
      in rheumatoid arthritis (RA), JA sCD21 levels were normal. sCD21 levels did not
      correlate with clinical parameters and immunophenotype of synovial cells. CD4 T
      cells in the synovium were almost all of the CD45RO memory type and 13 of 40
      patients displayed synovial expansion of gammadeltaT cells. CD21 shedding in JA
      differs from RA/SS/SLE. JA sCD21 levels in synovial fluid are always lower
      compared to blood levels of the same patients. Analysis of JA synovial T cells
      indicates a T-cell driven response.

PMID- 15584975
TI  - Gene expression in human macrophages infected with dengue virus serotype-2.
AB  - Infection by any of the four serotypes of dengue viruses (DEN-1, -2, -3 and -4)
      may result in either a relatively benign fever, called dengue fever (DF), a fatal
      disease, such as dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS).
      Several lines of evidence suggest that soluble immune response mediators may be
      involved in the severity of dengue infections. For instance, elevated seric
      levels of IL-8 are a common feature in DHF patients. Because other chemokines,
      cytokines, adhesion molecules, chemokine and cytokine receptors, as well as
      cytokine-related molecules may also be involved in dengue virus pathogenesis, we
      aimed at analysing the gene expression of such molecules in the course of an in
      vitro DEN-2 infection of human peripheral blood monocyte-derived macrophages, a
      cell type regarded as a primary target for DEN. Nylon membrane gene arrays
      containing 375 different human cytokine-related genes were used as a first step
      to search for differentially expressed genes upon infection. Transcripts for IL
      8, IL-1beta, osteopontin, GRO-alpha, -beta and -gamma, I-309, and some other
      molecules showed to be upregulated upon infection, whereas others such as MIC-1,
      CD27L and CD30L, were downregulated. Four genes were selected for reverse
      transcriptase-polymerase chain reaction based gene-expression analysis as a way
      to partially confirm microarray results. This approach pointed out 25 macrophage
      expressed cytokine-related genes that could be relevant in DEN-2 pathogenesis.

PMID- 15584976
TI  - Cortisol and dehydroepiandrosterone affect the response of peripheral blood
      mononuclear cells to mycobacterial antigens during tuberculosis.
AB  - The effect of cortisol and/or dehydroepiandrosterone (DHEA) on the immune
      response to antigens obtained from Mycobacterium tuberculosis was studied in
      vitro by using peripheral blood mononuclear cells obtained from patients at
      various stages of lung tuberculosis (TB) and from healthy control people (HCo).
      The results obtained show for the first time that addition of cortisol within
      concentrations of physiological range can inhibit the mycobacterial antigen
      driven proliferation of cells from HCo and TB patients and the production of
      interferon-gamma (IFN-gamma), indicating that endogenous levels of cortisol may
      contribute to the decreased lymphoid cell response to mycobacterium antigens
      observed in TB patients. DHEA did not affect lymphoid cell proliferation, IFN
      gamma production and the cortisol-mediated inhibitory effects. Interestingly, we
      found that DHEA, but not cortisol, suppressed the in vitro transforming growth
      factor-beta production by lymphoid cells from TB patients with an advanced
      disease, which is indicative of a selective direct effect of this hormone.

PMID- 15584977
TI  - Poor in vitro maturation and pro-inflammatory cytokine response of dendritic
      cells in children at genetic risk of type 1 diabetes.
AB  - Type 1 diabetes (T1D) has been associated with an aberrant maturation of
      dendritic cells (DC). We studied the maturation of monocyte-derived DC in
      children with newly diagnosed T1D and in healthy children with genetic risk for
      T1D. Peripheral blood monocytes from children with newly diagnosed T1D (n = 12;
      mean age 13.2 years), children with human leukocyte antigen (HLA)-risk genotype
      of T1D (n = 7; mean age 12.7 years) and healthy children (n = 14; mean age 11.2
      years) were in vitro differentiated into DC. Expression of HLA-DR, CD80/86 and
      CD11c and secretion of interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, IL
      6 and IL-10 were measured using flow cytometry. Lower percentage of DC expressed
      CD11c and HLA-DR, and decreased production of TNF-alpha was found in children
      with newly diagnosed T1D and in children at genetic risk when compared to healthy
      children. Children with risk genotype also had decreased IL-12 production by DC.
      Children with T1D and children at genetic risk of T1D appear to have similar
      aberrancies in the maturation of DC, which may predispose to beta-cell
      autoimmunity.

PMID- 15584978
TI  - Transfusion medicine illustrated. Hemophagocytosis and coagulopathy associated
      with cutaneous gamma-delta T-cell lymphoma.

PMID- 15584979
TI  - Low-dose prophylactic platelet transfusions: time for further study, but too
      early for routine clinical practice.

PMID- 15584980
TI  - Recipients of blood from a donor with multiple HLA antibodies: a lookback study
      of transfusion-related acute lung injury.
AB  - BACKGROUND: The effects of transfusion of HLA antibodies to patients with
      corresponding antigens are not well known. STUDY DESIGN AND METHODS: Records of
      patients who received blood from previous donations of a donor implicated in a
      case of transfusion-related acute lung injury (TRALI) were examined. The donor
      had multiple HLA antibodies reactive with 96 percent of HLA Class I antigens and
      88 percent of HLA Class II antigens. RESULTS: Among 103 patients (40 with a
      pretransfusion white blood cell [WBC] count of >/=3.5 x 10(9)/L), 1 patient met
      criteria for TRALI and had clinical evidence for diffuse alveolar hemorrhage.
      Among the subset of 55 patients (17 with a pretransfusion WBC count of 3.5 x
      10(9)/L) with known HLA types, none developed TRALI even though 54 (98%) had one
      to five corresponding HLA antigens. In a subgroup of patients four of 62 patients
      with chest radiographs, developed new or worse bilateral infiltrates with
      implicated but not control units (p = 0.0625). CONCLUSION: Transfusion of HLA
      antibodies from this donor to nonneutropenic patients did not cause TRALI, but
      there was a trend of an association with new or worse bilateral pulmonary
      infiltrates. Further research is needed to determine why transfusion of HLA
      antibodies to recipients with corresponding antigens causes TRALI in some cases
      and not in others.

PMID- 15584981
TI  - Acute and transient decrease in neutrophil count in transfusion-related acute
      lung injury: cases at one hospital.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare but serious
      complication of blood transfusion. The syndrome is characterized by new acute
      lung injury developing during or within 6 hours of blood transfusion. STUDY
      DESIGN AND METHODS: The study design was observational in nature. RESULTS: All
      three cases of TRALI were associated with acute but transient decrease in the
      white blood cell (WBC) count. Implicated donors had HLA antibodies that matched
      the recipients' HLA antigens. The implicated units were a plateletpheresis in one
      case and fresh frozen plasma units in the other two. All implicated donors were
      multiparous women. The implicated antibody specificities were anti-HLA Class I
      and Class II in one case and anti-HLA Class II in the other two cases.
      Interestingly, patient neutrophil counts decreased by 80 to 90 percent in all
      three cases, including the two cases associated with HLA Class II antibodies.
      CONCLUSION: An acute and transient decrease in WBC count may be a previously
      underrecognized feature of TRALI. A drop in the neutrophil count can occur even
      when the implicated antibodies have specificities to HLA Class II antigens,
      although they are expressed only on stimulated neutrophils. Based on the
      observations in these cases, it is recommended that a complete blood count and
      differential be obtained when TRALI is suspected. Further investigations into the
      mechanisms of the decrease in circulating neutrophils that is associated with
      infusion of HLA Class II antibody may yield new insights into the mechanism of
      TRALI.

PMID- 15584982
TI  - West Nile virus blood transfusion-related infection despite nucleic acid testing.
AB  - BACKGROUND: A case of West Nile virus (WNV) encephalitis associated with
      transfusion of blood that did not react when tested for WNV by minipool (MP)
      nucleic acid testing (NAT) is described. A Nebraska man developed clinical
      encephalitis 13 days after surgery and transfusion of 26 blood components.
      Antibody testing confirmed WNV infection. An investigation was initiated to
      determine the source of this infection. STUDY DESIGN AND METHODS: The patient's
      family members were interviewed to identify risk factors for WNV infection.
      Residual samples were retested for WNV RNA using transcription-mediated
      amplification (TMA) assay and two polymerase chain reaction (PCR) assays. Blood
      donors' follow-up serum samples were collected. All samples were tested for WNV
      specific immunoglobulin M antibodies. RESULTS: The patient's family denied recent
      mosquito exposure. The 20 blood components collected after July 2003 did not
      react when tested for WNV in a six-member MP-NAT at the time of donation.
      Retrospective individual testing identified one sample as WNV-reactive by the TMA
      assay and one of the PCR assays. Seroconversion was demonstrated in the donor
      associated with this sample. CONCLUSION: WNV RNA detection by individual donation
      NAT demonstrates viremic blood escaping MP-NAT and supports transfusion-related
      WNV transmission. MP-NAT may not detect all WNV-infected blood donors, allowing
      WNV transmission to continue at low levels. WNV NAT assays might vary in
      sensitivity and pooling donations could further impact test performance.
      Understanding MP NAT limitations can improve strategies to maintain safety of the
      blood supply in the United States.

PMID- 15584983
TI  - Effect of protease treatment on plasma infectivity in variant Creutzfeldt-Jakob
      disease mice.
AB  - BACKGROUND: The emergence of variant Creutzfeldt-Jakob disease (vCJD) and of a
      probable transmission of the disease through blood transfusion from a
      presymptomatic case has underlined the need for a reliable, sensitive, and
      specific screening test. This study was initiated to explain why attempts to
      identify protease-resistant prion protein (PrPres) following treatment with
      proteinase K (PK) in blood or blood components have so far failed. STUDY DESIGN
      AND METHODS: RIII mice were inoculated intracerebrally (i.c.) with vCJD agent. As
      soon as some mice became ill, blood from all mice was collected, pooled, and
      separated into components. Aliquots of plasma were treated with either 100 and
      500 microg per mL PK or left untreated. Samples were analyzed for total protein
      and for PrPres by Western blot with 6H4 antibodies. Infectivity in PK-treated and
      untreated samples was bioassayed by i.c. inoculation into healthy mice. RESULTS:
      Estimated infectivity in untreated control plasma was 20.6 IU per mL. Treatment
      of plasma with 100 or 500 microg per mL PK resulted in estimated infectivity
      levels of 8.4 and 5.2 IU per mL, respectively. Coomassie staining revealed
      substantial changes in the protein profile after PK treatment, with massive
      degradation of proteins at 500 microg per mL PK. No PrPres was detected in plasma
      samples by Western blotting. CONCLUSION: Infectivity in plasma of vCJD-infected
      mice showed a trend toward reduction following enzymatic treatment with
      increasing doses of PK, possibly because of activity against proteolysis
      sensitive isoforms of abnormal prion protein. It is concluded that the use of PK
      in protocols for the detection of PrPres may decrease the sensitivity of blood
      based assays.

PMID- 15584984
TI  - The hepatitis C virus genotype and subtype frequency in hepatitis C virus RNA
      positive, hepatitis C virus antibody-negative blood donors identified in the
      nucleic acid test screening program in Poland.
AB  - BACKGROUND: Since 2002, blood donors in Poland have been tested not only for
      hepatitis C virus antibodies (anti-HCV) but also for HCV RNA or HCV core antigen.
      This screening program identifies asymptomatic, recently infected individuals
      with no anti-HCV (in the "window period"). The aim of this study was to compare
      HCV genotype and subtype distribution in window-period (wp) donors, anti-HCV
      positive donors, and chronic hepatitis C (CHC) patients. STUDY DESIGN AND
      METHODS: A total of 2.37 million donors were investigated for HCV RNA, and
      340,000 for HCV core antigen. HCV genotypes and subtypes were investigated in 50
      HCV RNA-positive, anti-HCV-negative donors; in 70 anti-HCV-positive donors; and
      in 170 CHC patients. Re-questioning of wp donors for probable risk factors was
      introduced. RESULTS: HCV RNA was detected in 50 donors of 2.71 million (1:54,200)
      anti-HCV-negative blood donations. Of these 50 donors, 36 percent exhibited
      Subtype 1b, whereas Subtypes 3a and 4c/d were identified in 40 and 14 percent,
      respectively. In anti-HCV-positive donors and CHC patients, the frequency of
      Subtype 1b was significantly higher (75.7 and 85.3%, respectively); in both
      groups the lower frequency of Subtypes 3a (14.3 and 10.6%, respectively) and 4c/d
      (4.3 and 1.2%, respectively) was found. The probable source of infection was
      identified in 9 wp donors. CONCLUSIONS: The frequency of wp donors is 18.5 per 1
      million. The unexpected high frequency of Genotype 4 and Subtype 3a and the low
      frequency of Subtype 1b was observed in wp donors compared to anti-HCV-positive
      individuals. Additional epidemiologic questioning introduced after HCV RNA
      detection may help to identify infection source.

PMID- 15584986
TI  - Prevention of immunization to D+ red blood cells with red blood cell exchange and
      intravenous Rh immune globulin.
AB  - BACKGROUND: Although young women who are D- occasionally receive unintentional
      transfusions with D+ red blood cells (RBCs), there are little data to assist with
      management of such an event. Two cases of D- girls transfused with D+ RBCs are
      reported. In an effort to prevent formation of anti-D, RBC exchange followed by
      administration of intravenous (IV) Rh immune globulin (RhIg) was used. CASE
      REPORTS: Patient 1, a 56-kg, 16-year-old D- girl, was involved in a motor vehicle
      crash. She received 4 units of Group O uncrossmatched D+ RBCs. Thirty-six hours
      after admission, she underwent RBC exchange with 10 units of D- RBCs, followed by
      a total of 2718 microg of IV RhIg over 32 hours. Six months later, her antibody
      screen was negative. Patient 2, a 39-kg, 10-year-old D- girl with aplastic
      anemia, received 1 unit of D+ RBCs. She underwent RBC exchange on the same day
      with 5 units of D- RBCs, followed by a total of 900 microg of IV RhIg over 8
      hours. Six months later her antibody screen was negative. CONCLUSION: RBC
      exchange followed by a calculated dose of IV RhIg was successful in preventing
      allo-immunization to D. Several small studies suggest that both trauma and
      hematology patients may be less capable of becoming immunized with the
      transfusion of D+ blood components. Until these findings are more clearly
      defined, there will be times when prevention of immunization of any D- girl is
      desired. RBC exchange followed by RhIg appears to be one way to achieve this
      goal.

PMID- 15584985
TI  - Low-dose prophylactic platelet transfusions in recipients of an autologous
      peripheral blood progenitor cell transplant and patients with acute leukemia: a
      randomized controlled trial with a sequential Bayesian design.
AB  - BACKGROUND: Prophylactic platelet (PLT) transfusions are standard treatment for
      patients receiving high-dose chemotherapy, but the optimal dose is not known. A
      randomized controlled trial was undertaken to examine the effectiveness of low
      dose PLT transfusions and to determine the need for further studies. STUDY DESIGN
      AND METHODS: Patients (n = 111) with acute leukemia or undergoing autologous
      peripheral blood progenitor cell (PBPC) transplantation were randomly assigned to
      receive low-dose (3 PLT units) or standard-dose (5 PLT units) prophylactic PLT
      transfusions and were monitored daily for bleeding. Using a sequential Bayesian
      design, the difference in major bleeding events was determined. RESULTS: The
      percentage of patients with major bleeding events was 10.7 percent (95% credible
      region, 5.1%-21.2%) in the low-dose PLT group and 7.3 percent (95% credible
      region, 2.9%-17.2%) in the standard-dose PLT group. The two additional events in
      the low-dose group occurred when the PLT count exceeded 100 x 10(9) per L. There
      is an 89 percent probability that the absolute increase in major bleeds is less
      than 10 percent with low-dose PLT transfusions. The number of minor bleeding
      events was higher in the standard-dose group. Patients receiving low-dose PLT
      transfusions received 25 percent fewer PLT units. There was an 89 percent
      probability that low-dose transfusions reduced PLT utilization in patients with
      acute leukemia and a 60 percent probability in patients undergoing PBPC
      transplantation. CONCLUSION: Low-dose PLT transfusions appear to be safe and
      effective and reduce PLT utilization. They should be further evaluated in
      clinical trials designed to evaluate equivalency.

PMID- 15584987
TI  - Epitheliotrophic capacity of a growth factor preparation produced from platelet
      concentrates on corneal epithelial cells: a potential agent for the treatment of
      ocular surface defects?
AB  - BACKGROUND: Topical application of serum eye drops has been reported to
      accelerate healing of persistent ocular surface defects. It is supposed that
      growth factors in serum support the wound healing process. Platelets (PLTs) are
      rich in growth factors and easily available as PLT concentrates (PCs) from blood
      banks. Therefore, growth factor preparations from PCs may serve as a new and
      superior therapeutic agent for such defects. STUDY DESIGN AND METHODS: After
      thrombin stimulation for growth factor release, the cell-free supernatant (PLT
      releasate) of washed PCs (n = 8) was analyzed for epitheliotrophic factors and
      its wound healing capacity in comparison to serum (n = 8). Human corneal
      epithelial cells were used as a model to investigate cell growth, migration, and
      differentiation in response to both blood products. RESULTS: PLT releasate
      contains more epithelial growth factor, PLT-derived growth factor, and
      transforming growth factor-beta, but less hepatocyte growth factor, fibronectin,
      and vitamins. Cell growth was significantly better in response to PLT releasate.
      Migration and differentiation were slightly better supported by serum.
      CONCLUSION: Possibly owing to its high content of growth factors, PLT releasate
      has a distinct superior effect on cell growth. Stimulation of migration and
      differentiation was slightly inferior but still acceptable. PLT releasate could
      therefore be a novel treatment option for ocular surface defects.

PMID- 15584988
TI  - Recovery and life span of 111indium-radiolabeled platelets treated with pathogen
      inactivation with amotosalen HCl (S-59) and ultraviolet A light.
AB  - BACKGROUND: A photochemical treatment (PCT) method to inactivate pathogens in
      platelet concentrates has been developed. The system uses a psoralen, amotosalen
      HCl, coupled with ultraviolet A (UVA) illumination. STUDY DESIGN AND METHODS:
      Three sequential clinical trials evaluated viability of PCT platelets prepared
      with a prototype device. Posttransfusion recovery and lifespan of (111)Indium
      labeled autologous 5 day-old platelets in healthy subjects was assessed. In the
      first study, 23 subjects received transfusions of autologous PCT and/or control
      platelets. In a second study, 16 of these subjects received PCT platelets
      processed with a Compound Adsorption Device (CAD) (PCT-CAD) to reduce patient
      exposure to residual amotosalen. In the third study, the effect of gamma
      irradiation on PCT platelets was studied. Data from control transfusions from
      Study A were used for paired comparisons in the latter 2 studies. RESULTS: Mean
      PCT-CAD platelet recovery for the 16 subjects with paired data was 42.5 +/- 8.7%
      versus 50.3 +/- 7.7% for control platelets, mean difference of 7.8% (p < 0.01).
      Mean lifespan for PCT-CAD platelets was 4.8 days (+/-1.3) versus 6.0 days (+/
      1.2) for control platelets, mean difference of 1.3 days (p < 0.01). Platelet
      recovery and lifespan were similar to PCT-CAD for PCT without CAD treatment and
      PCT-CAD with gamma-irradiation. CONCLUSION: Viability of 5 day-old PCT platelets
      was less than for control platelets. However, both were within ranges reported
      for 5 day-old platelets.

PMID- 15584989
TI  - Transcriptional regulation of the human ABO histo-blood group genes is dependent
      on the N box upstream of the proximal promoter.
AB  - BACKGROUND: Our previous studies of the transcriptional regulation of the human
      ABO gene indicated that negative regulatory elements are present in the sequence
      just upstream from the proximal promoter. The role of the -275 to -118 region in
      regulation of ABO gene transcription is further characterized. STUDY DESIGN AND
      METHODS: Transient transfection experiments into various cells were performed
      with luciferase reporter plasmids carrying ABO upstream sequences, and
      electrophoretic mobility shift assay was carried out with a nuclear extract
      prepared from the human gastric cancer KATOIII cells. RESULTS: It is shown that
      the -202 to -118 region is involved in the negative regulation of ABO gene
      transcription in all cell lines examined. Transient transfection experiments in
      KATOIII cells with a reporter plasmid carrying mutated N box at -196 to -191
      demonstrate that the N box is a negative regulatory element in the -202 to -118
      sequence. Electrophoretic mobility shift assays indicate that the N box binds
      with a nuclear factor from KATOIII cells. CONCLUSION: These results indicate that
      repression of transcription from the ABO proximal promoter is partially dependent
      upon the N box. Therefore, reduced binding of the protein with the N box might
      play a direct role in ABO gene expression.

PMID- 15584990
TI  - Resolution of a serum sample mix-up through the use of short tandem repeat DNA
      typing.
AB  - BACKGROUND: A sample mix-up occurred in a tissue procurement laboratory in which
      aliquots of serum from two tissue donors were accidentally mislabeled. The clues
      to the apparent mixup involved discrepant Hepatitis C test results. In an attempt
      to resolve the apparent mix up, DNA typing was performed using serum samples as a
      possible source of genomic DNA. STUDY DESIGN AND METHODS: Two hundred microliter
      aliquots of two reference sera and aliquots prepared from them were subjected to
      DNA extraction. PCR amplification of 9 STR loci was performed on the extracts and
      amplicons were analyzed by capillary electrophoresis. RESULTS: About 1 microg/ml
      of DNA was recovered from all serum samples and was of sufficient quality to
      direct the amplification of most, if not all STR loci allowing the mislabeled
      specimens to be traced to the proper tissue donor. CONCLUSIONS: Serum is a useful
      source of genomic DNA for STR analysis in situations in which such samples are
      the only source of DNA for testing. Interestingly, one of the tissue donors on
      life support and repeatedly receiving blood products, exhibited a mixed DNA
      profile indicative of the presence of DNA from multiple individuals in the
      bloodstream.

PMID- 15584991
TI  - Detection of free hepatitis C virus core antigen by enzyme-linked immunosorbent
      assay is not suitable for screening of granulocyte colony-stimulating factor
      mobilized hematopoietic progenitor donors.
AB  - BACKGROUND: Recent studies have shown that hepatitis C virus (HCV) can be
      detected in peripheral blood mononuclear cells of patients who are negative for
      the presence of anti-HCV and serum HCV RNA. The aim of the study was to evaluate
      the prevalence of HCV viremia in granulocyte colony-stimulating factor (G-CSF)
      mobilized peripheral blood progenitor cell (PBPC) donors by the use of a free HCV
      core antigen enzyme-linked immunosorbent assay (ELISA). STUDY DESIGN AND METHODS:
      A total of 28 samples from consecutive PBPC donors that were mobilized with G
      CSF, and 13 samples from patients presenting with leukocytosis of greater than 20
      x 10(9) per L from other causes, were tested by a free HCV core antigen ELISA.
      Positive samples were confirmed by use of neutralization assays. The specificity
      of the assay was studied in 48,911 healthy blood donors negative for the presence
      of anti-HCV. RESULTS: The free HCV core antigen assay showed a 46.4 percent
      positivity in PBPC donors mobilized with G-CSF and 61.5 percent in patients
      exhibiting leukocytosis in the absence of G-CSF treatment. All the samples were
      found to be false-positive samples, and those related with growth factor
      treatment did not react when G-CSF was discontinued. Overall specificity by the
      test in freshly collected blood donor specimens was 99.62 percent. CONCLUSION:
      Data indicate that the free HCV core antigen ELISA is not a valid test in
      diagnosing HCV infection in G-CSF-treated PBPC donors. Moreover, false-positive
      results of this test on blood donors might be indicative of elevated white blood
      cell numbers. The low specificity of this assay in the PBPC mobilization setting
      suggests that molecular assays should be the test of choice in the screening of G
      CSF-treated donors.

PMID- 15584992
TI  - Initiation of peripheral blood progenitor cell harvest based on peripheral blood
      hematopoietic progenitor cell counts enumerated by the Sysmex SE9000.
AB  - BACKGROUND: The most reliable index for timing peripheral blood progenitor cell
      (PBPC) collection following mobilization is still to be determined. The
      techniques to enumerate peripheral blood (PB) CD34+ cells are expensive and time
      consuming. The SE9000 (Sysmex) provides an estimate of immature cells, called
      hematopoietic progenitor cells (HPCs). The aim of this study was to prospectively
      evaluate the efficacy of PB HPC levels for timing PBPC harvest. STUDY DESIGN AND
      METHODS: Thirty-five patients (15 non-Hodgkin's lymphoma and 20 multiple myeloma)
      were enrolled. PB HPCs and harvested CD34+ cells were counted with the SE9000 and
      flow cytometry, respectively. Circulating HPCs were monitored daily. PBPC harvest
      was initiated when HPC levels reached at least 5 per mm(3). RESULTS: HPC levels
      reached 5 per mm(3) or more on Median Day 12 (range, days 9 to 16) of mobilizing
      chemotherapy. The median number of CD34+ cells collected per patient was 19.40 x
      10(6) per kg (range, 1.94 x 10(6)-52.55 x 10(6) per kg). Both successful and
      optimal harvest was achieved in 97 percent of patients. PBPCs were successfully
      harvested in 25 patients (71%) in one session. An optimal harvest in a single
      session was attained in 16 patients (46%). CONCLUSION: This might be the first
      prospective study showing the PB HPC level for timing PBPC harvest.

PMID- 15584993
TI  - Good and poor mobilizing patients differ in mobilized CD34+ cell adhesion
      molecule profiles.
AB  - BACKGROUND: Alterations in expression of adhesion molecules are important in the
      trafficking of hematopoietic progenitors and probably in the mobilization
      process. Relatively little and conflicting data are currently available on the
      differences in expression between good and poor mobilizing patients. STUDY DESIGN
      AND METHODS: In this study, the expression of eight adhesion molecules on the
      collected CD34+ cells from 36 patients undergoing mobilization was determined.
      RESULTS: Good mobilizing patients, defined as those who collected their target in
      one apheresis procedure, had significantly fewer cells that expressed CD11a (LFA
      1) and CD54 (ICAM-1) and borderline fewer that expressed CD11c, CD49d (VLA-4),
      and CD49d (VLA-5). No differences were detected in CD11b (Mac-1), CD15s (sLe(x)),
      or CD62L (L-selectin). Linear regression analysis identified number of prior
      chemotherapy courses and expression of CD11a (LFA-1) as independent predictive
      factors for mobilization efficiency. Good and poor mobilizing patients had
      approximately the same number of total CD34+ cells collected and little
      difference in times to engraftment. CONCLUSIONS: CD11a (LFA-1) expression
      inversely correlates with mobilization efficiency. Elucidation of the
      mechanism(s) underlying these observations will require further study.

PMID- 15584994
TI  - Toward an understanding of transfusion-related acute lung injury: statement of a
      consensus panel.

PMID- 15584995
TI  - Hemostatic effect of activated recombinant factor VIIa in Bernard-Soulier
      syndrome: studies in an in vitro model.

PMID- 15584996
TI  - Red blood cell fragmentation before hematopoietic progenitor cell
      transplantation.

PMID- 15584997
TI  - Production assistance for cellular therapies.

PMID- 15584999
TI  - Overview of blood conservation.

PMID- 15585000
TI  - Risks of transfusion: outcome focus.

PMID- 15585001
TI  - Strategies to optimize the use of erythropoietin and iron therapy in oncology
      patients.

PMID- 15585002
TI  - Acute normovolemic hemodilution.

PMID- 15585003
TI  - Autotransfusion theory of operation: a review of the physics and hematology.

PMID- 15585004
TI  - Indications and contraindications of cell salvage.

PMID- 15585005
TI  - Reasons against the retransfusion of unwashed wound blood.

PMID- 15585006
TI  - Perioperative apheresis.

PMID- 15585007
TI  - Hemostatic agents.

PMID- 15585008
TI  - A retrospective study comparing the histopathological features and response to
      treatment in two canine nasal dermatoses, DLE and MCP.
AB  - Canine discoid lupus erythematosus (DLE) and mucocutaneous pyoderma (MCP) have
      overlapping clinical and histopathological changes, often making diagnosis
      difficult. Histopathological features of 27 nasal planum biopsies were scored to
      determine whether DLE and MCP were histopathologically distinguishable. Long-term
      follow-up, enabling assessment of clinical diagnoses, was available on 15 cases;
      11/15 cases were immunomodulatory responsive (ImR) and 4/15 were antibiotic
      responsive (AbR). Clinical diagnosis, determined by response to treatment for
      15/27 cases, was not predictable based on scoring of histopathological features.
      Distinct histopathological patterns were observed: 2/11 ImR cases had a
      lymphocyte-rich interface dermatitis. All other cases had the same
      histopathological changes: a band-like diffuse superficial plasmacytic to
      lymphoplasmacytic dermatitis +/- focal basal cell damage, but different clinical
      diagnoses (4/4 AbR, 9/11 ImR). German shepherd dogs/crosses were over-represented
      (44.4% of the cases) and tended to have more multifocal lesions (41.7% vs. 26.7%
      of all other breeds). Longer duration of disease was associated with a
      preponderance of plasmacytic infiltrate (P = 0.026).